PMID- 21874088
TI  - The importance of indirect cues for white-browed sparrow-weaver (Plocepasser
      mahali) risk assessment.
AB  - Both direct cues that provide information about the actual presence of a predator
      and indirect environmental cues that provide information about the probability of
      encountering a predator may be used by animals assessing predation risk, but
      relatively few studies manipulate both simultaneously to study their relative
      importance. We conducted two experiments to study the foraging decisions of white
      browed sparrow-weavers (Plocepasser mahali). The first experiment manipulated
      both direct and indirect cues in a feeding array by simultaneously placing
      feeding stations at different distances from humans (to manipulate direct risk)
      and from protective cover (to manipulate indirect risk). Weaver foraging was
      influenced more by indirect risk than by direct risk. The second experiment aimed
      to determine if weaver's indirect risk assessment was sensitive to variation in
      benefits. We set two feeding stations at different distances from cover but the
      same distance from the human observers and systematically increased the amount of
      food at the station farther from cover. Weavers far from cover initially foraged
      at higher rates than those close to cover, but the addition of food reduced the
      foraging rate. Together, our results illustrate that weaver foraging decisions
      are sensitive to variation in risk and that indirect cues are relatively more
      important than direct cues.

PMID- 21874089
TI  - Perch exposure and predation risk: a comparative study in passerines.
AB  - Singing birds optimize signal transmission by perching in exposed locations.
      However, conspicuous singing may be risky, and previous research has found that
      individuals trade off singing performance with song perch exposure. We studied
      the relationship between predation risk (degree of concealment, height in tree or
      shrub, and distance to the forest edge) and time allocated to singing and
      vigilance in a group of 13 passerine species living in an East African savanna.
      Concealed birds sang more and were less vigilant. Vigilance increased as distance
      to the forested edge increased, but distance had no effect on time allocated to
      singing. Body size was significantly correlated with vigilance but not singing;
      larger passerines were more sensitive to both relative concealment and the
      distance to the forest edge, while song was influenced by neither of these
      factors. Perch height had no effect on either behavior. Our results suggest that
      birds modify vigilance and, to some extent, singing behavior to minimize their
      exposure to predators.

PMID- 21874090
TI  - The role of receptivity in the courtship behavior of Podocnemis erythrocephala in
      captivity.
AB  - The courtship behavior of Podocnemis erythrocephala (Red-headed Amazon River
      Turtle) in captivity was studied to examine female receptivity and male response
      to female rejection. We observed 20 females and 39 males in 150 sessions (3-6
      h/day for a total of 450 h). In 36% of the trials, there was no interaction
      between males and females, and 20% of the trials resulted in copulations. All
      males introduced into tanks approached females, and eventually there was
      aggression among the males. In 48% of the experiments, females also searched for
      or approached males. When males initially approached females, they either
      accepted the male's advances (14%), rejected the male passively (38%), or
      rejected the male aggressively (48%). In 86% of the cases where males were
      rejected, 4% attempted to approach females again, and in 51% they were ultimately
      successful.

PMID- 21874091
TI  - Examining Different Forms of Implementation and in Early Childhood Curriculum
      Research.

PMID- 21874092
TI  - The Impact of Child Care Subsidy Use on Child Care Quality.
AB  - In 2008, the federal government allotted $7 billion in child care subsidies to
      low-income families through the state-administered Child Care and Development
      Fund (CCDF), now the government's largest child care program (US DHHS, 2008).
      Although subsidies reduce costs for families and facilitate parental employment,
      it is unclear how they impact the quality of care families purchase. This study
      investigates the impact of government subsidization on parents' selection of
      child care quality using multivariate regression and propensity score matching
      approaches to account for differential selection into subsidy receipt and care
      arrangements. Data were drawn from the Child Care Supplement to the Fragile
      Families and Child Wellbeing Study (CCS-FFCWS), conducted in 2002 and 2003 in 14
      of the 20 FFCWS cities when focal children were 3 years old (N = 456). Our
      results indicate that families who used subsidies chose higher quality care than
      comparable mothers who did not use subsidies, but only because subsidy recipients
      were more likely to use center-based care. Subgroup analyses revealed that
      families using subsidies purchased higher-quality home-based care but lower
      quality center-based care than comparable non-recipients. Findings suggest that
      child care subsidies may serve as more than a work support for low-income
      families by enhancing the quality of nonmaternal care children experience but
      that this effect is largely attributable to recipients' using formal child care
      arrangements (versus kith and kin care) more often than non-recipients.

PMID- 21874093
TI  - III. Co-electrodeposition/removal of copper and nickel in a spouted
      electrochemical reactor.
AB  - Results are presented of an investigation of co-electrodeposition of copper and
      nickel from acidic solution mixtures in a cylindrical spouted electrochemical
      reactor. The effects of solution pH, temperature, and applied current on metal
      removal/recovery rate, current efficiency, and corrosion of the deposited metals
      from the cathodic particles were examined under galvanostatic operation. The
      quantitative and qualitative behavior of co-electrodeposition of the two metals
      from their mixtures differs significantly from that of the individual single
      metal solutions. This is primarily attributed to the metal displacement reaction
      between Ni(0) and Cu(2+). This reaction effectively reduces copper corrosion, and
      amplifies that for nickel (at least at high concentrations). It also amplifies
      the separation of the deposition regimes of the two metals in time, which
      indicates that the recovery of each metal as a relatively pure deposit from the
      mixture is possible. It was also shown that nitrogen sparging considerably
      increases the observed net electrodeposition rates for both metals - considerably
      more so than from solutions with just the single metals alone. A numerical model
      of co-electrodeposition, corrosion, metal displacement, and mass transfer in the
      cylindrical spouted electrochemical reactor is presented that describes the
      behavior of the experimental copper and nickel removal data quite well.

PMID- 21874094
TI  - Population, Health, and Environment Through a "Gendered" Lens: When women are
      better off, so are populations.

PMID- 21874095
TI  - Listeners' knowledge of phonological universals: Evidence from nasal clusters.
AB  - Optimality Theory explains typological markedness implications by proposing that
      all speakers possess universal constraints penalizing marked structure,
      irrespective of the evidence provided by their language (Prince & Smolensky,
      1993/2004). An account of phonological perception sketched here entails that
      markedness constraints reveal their presence by inducing perceptual 'repairs' to
      structures ungrammatical in the hearer's language. As onset clusters of falling
      sonority are typologically marked relative to those of rising sonority
      (Greenberg, 1978), we examine English speakers' perception of nasal-initial
      clusters-lacking in English. We find greater accuracy for rising-sonority
      clusters, evidencing knowledge of markedness constraints favoring such onset
      clusters. The misperception of sonority falls cannot be accounted for by stimulus
      artifacts (the materials are perceived accurately by speakers of Russian-a
      language allowing nasal-initial clusters) nor by phonetic failure (English
      speakers misperceive falls even with printed materials) nor by putative relations
      of such onsets to the statistics of the English lexicon.

PMID- 21874096
TI  - Microfluidic proportional flow controller.
AB  - Precise flow control in microfluidic chips is important for many biochemical
      assays and experiments at microscale. While several technologies for controlling
      fluid flow have been implemented either on- or off-chip, these can provide either
      high-speed or high-precision control, but seldom could accomplish both at the
      same time. Here we describe a new on-chip, pneumatically activated flow
      controller that allows for fast and precise control of the flow rate through a
      microfluidic channel. Experimental results show that the new proportional flow
      controllers exhibited a response time of approximately 250 ms, while our
      numerical simulations suggest that faster actuation down to approximately 50 ms
      could be achieved with alternative actuation schemes.

PMID- 21874097
TI  - Goal-Driven Cognition and Functional Behavior: The Fundamental-Motives Framework.
AB  - Fundamental motives have direct implications for evolutionary fitness and
      orchestrate attention, memory, and social inference in functionally specific
      ways. Motivational states linked to self-protection and mating offer illustrative
      examples. When self-protective motives are aroused, people show enhanced
      attention to, and memory for, angry male strangers; they also perceive out-group
      members as especially dangerous. In contrast, when mating motives are aroused,
      men show enhanced attention to and memory for attractive members of the opposite
      sex; mating motives also lead men (but not women) to perceive sexual arousal in
      attractive members of the opposite sex. There are further functionally specific
      consequences for social behavior. For example, self-protective motives increase
      conformity among both men and women, whereas mating motives lead men (but not
      women) to engage in anticonformist behavior. Other motivational systems trigger
      different adaptive patterns of cognitive and behavioral responses. This body of
      research illustrates the highly specific consequences of fitness-relevant
      motivational states for cognition and behavior, and highlights the value of
      studying human motivation and cognition within an evolutionary framework.

PMID- 21874098
TI  - NUMERICAL SIMULATION OF NANOINDENTATION AND PATCH CLAMP EXPERIMENTS ON
      MECHANOSENSITIVE CHANNELS OF LARGE CONDUCTANCE IN ESCHERICHIA COLI.
AB  - A hierarchical simulation framework that integrates information from all-atom
      simulations into a finite element model at the continuum level is established to
      study the mechanical response of a mechanosensitive channel of large conductance
      (MscL) in bacteria Escherichia Coli (E.coli) embedded in a vesicle formed by the
      dipalmitoylphosphatidycholine (DPPC) lipid bilayer. Sufficient structural details
      of the protein are built into the continuum model, with key parameters and
      material properties derived from molecular mechanics simulations. The multi-scale
      framework is used to analyze the gating of MscL when the lipid vesicle is
      subjective to nanoindentation and patch clamp experiments, and the detailed
      structural transitions of the protein are obtained explicitly as a function of
      external load; it is currently impossible to derive such information based solely
      on all-atom simulations. The gating pathways of E.coli-MscL qualitatively agree
      with results from previous patch clamp experiments. The gating mechanisms under
      complex indentation-induced deformation are also predicted. This versatile
      hierarchical multi-scale framework may be further extended to study the
      mechanical behaviors of cells and biomolecules, as well as to guide and stimulate
      biomechanics experiments.

PMID- 21874099
TI  - Artifact reduction in truncated CT using Sinogram completion.
AB  - Truncation of projection data in CT produces significant artifacts in the
      reconstruction process due to non-locality of the Radon transform. In this paper,
      we present a method for reducing these truncation artifacts by estimating
      features that lie outside the region of interest (ROI) and using these features
      to complete the truncated sinogram.Projection images of an object are obtained. A
      sinogram is obtained by stacking profile data from all projection angles. A
      simulated truncated sinogram is generated by setting pixel values outside an ROI
      to zero. The truncated sinogram is then transformed into a (radius, phase) image,
      with pixel values in what we term as the Polar representation (PR) image
      corresponding to the minimum value along sine curves given by x =
      r*cos(projection angle + phase). The PR image contains data for radii greater
      than the ROI radius. Pixel values outside the ROI in the completed sinogram are
      determined as follows. For each pixel in the PR image, a sine curve is generated
      in the completed sinogram image outside the ROI, having the same pixel value as
      that of the PR image for that radius and phase. Successive sine curves are laid
      and the values of each are summed. The intensity outside is then equalized to the
      intensity inside the ROI. The completed sinogram is then reconstructed, to obtain
      completed reconstruction.The percentage error in the difference image between the
      full FOV reconstruction and the corresponding completed reconstruction and the
      extrapolated-average reconstruction are 1.1% and 3.3% respectively. This
      indicates that the completed reconstruction is closer to full FOV reconstruction.
      Thus, the sinogram completion can be used to improve reconstructions from
      truncated data.

PMID- 21874100
TI  - FEA of CMUTs Suitable for Wide Gas Pressure Range Applications.
AB  - The ability of ultrasound transducers to operate over a wide and varying pressure
      range is essential in applications such as ultrasonic flow metering (UFM) of
      flare gas. We propose a new operational mode for capacitive micromachined
      ultrasonic transducers (CMUTs), in which the plate is in permanent contact with
      the bottom of the cavity, even at zero DC bias and 1 atm pressure. Finite element
      analysis (FEA) software was used to investigate the performance of these CMUTs
      within the pressure range of 1 to 20 atm. First, we performed a static analysis
      to determine the plate deflection and, thus, the gap height. Further, from the
      static analysis, we obtained the static and free capacitances for calculating the
      coupling efficiency, and a modal analysis identified possible design geometries
      for frequencies lower than ~ 300 kHz. Our calculations show that conventionally
      operated CMUTs have huge changes in static operational point at different
      pressures, while our proposed mode exhibits an acceptable frequency range (73 -
      340 kHz) over 1 - 20 atm pressure and an improved coupling efficiency at lower dc
      bias voltages. A donut shape partial electrode further allows us to tune the
      coupling efficiency, which translates into a better performance, especially at
      the higher pressure range. FEA shows that our proposed operation mode is a
      promising solution for flare gas metering applications.

PMID- 21874101
TI  - Substance Use, Criminal Activity, and Mental Health Among Violent and Nonviolent
      Rural Probationers.
AB  - Differences between violent and nonviolent probationers were examined in the
      growing, yet understudied, rural probation population. Violent rural probationers
      had higher rates of substance use, criminal activity, and mental health symptoms
      than did nonviolent rural probationers. Implications for practitioners are
      discussed.

PMID- 21874102
TI  - Design Principles for Rapid Prototyping Forces Sensors using 3D Printing.
AB  - Force sensors provide critical information for robot manipulators, manufacturing
      processes, and haptic interfaces. Commercial force sensors, however, are
      generally not adapted to specific system requirements, resulting in sensors with
      excess size, cost, and fragility. To overcome these issues, 3D printers can be
      used to create components for the quick and inexpensive development of force
      sensors. Limitations of this rapid prototyping technology, however, require
      specialized design principles. In this paper, we discuss techniques for rapidly
      developing simple force sensors, including selecting and attaching metal
      flexures, using inexpensive and simple displacement transducers, and 3D printing
      features to aid in assembly. These design methods are illustrated through the
      design and fabrication of a miniature force sensor for the tip of a robotic
      catheter system. The resulting force sensor prototype can measure forces with an
      accuracy of as low as 2% of the 10 N measurement range.

PMID- 21874103
TI  - Childhood Development and Access to Nature: A New Direction for Environmental
      Inequality Research.
AB  - Although environmental inequality researchers have increased our understanding of
      race- and class-based environmental inequality in many important ways, few
      environmental inequality studies ask whether children are disproportionately
      burdened by environmental pollution or whether poor and minority youth are less
      likely than their White and wealthier counterparts to spend time in green spaces
      and the natural world. This gap in the literature undermines the ability of
      researchers to fully understand and explain environmental inequality. To
      demonstrate the importance of filling this gap, the authors (a) highlight current
      research findings from the environmental health, environmental education, and
      environmental psychology literatures regarding the cognitive, emotional, and
      physical importance of childhood exposure to nature and (b) summarize the few
      existing studies that have examined class- and race-based inequalities in
      children's exposure to the natural world and industrial environmental hazards.
      The authors then suggest several avenues of research that would, if undertaken,
      significantly increase our understanding of youth-based environmental inequality.
      By synthesizing findings across multiple disciplines, the authors hope to
      convince environmental inequality researchers of the importance of investigating
      children's differential exposure to nature, green spaces, and industrial
      environmental hazards.

PMID- 21874104
TI  - Is friendship akin to kinship?
AB  - Although unrelated friends are genetically equivalent to strangers, several lines
      of reasoning suggest that close friendship may sometimes activate processes more
      relevant to kinship and that this may be especially true for women. We compared
      responses to strangers, friends, and kin in two studies designed to address
      distinct domains for which kinship is known to have functional significance:
      incest avoidance and nepotism. Study 1 examined emotional responses to imagined
      sexual contact with kin, friends, and strangers. Results revealed that women,
      compared to men, treated friends more like kin. Study 2 examined benevolent
      attributions to actual kin, friends, and strangers. Results revealed that women
      treated friends very much like kin, whereas men treated friends very much like
      strangers. The current findings support a domain-specific over a domain-general
      approach to understanding intimate relationships and raise a number of
      interesting questions about the modular structure of cognitive and affective
      processes involved in these relationships.

PMID- 21874105
TI  - Religious Attendance as Reproductive Support.
AB  - We argue that a central function of religious attendance in the contemporary U.S.
      is to support a high-fertility, monogamous mating strategy. Although religious
      attendance is correlated with many demographic, personality, moral, and
      behavioral variables, we propose that sexual and family variables are at the core
      of many of these relationships. Numerous researchers have assumed that religious
      socialization causes people to feel moral reactions and engage in behaviors
      promoted by religious groups. On our view, mating preferences are centrally
      involved in individual differences in attraction to religious groups. In a sample
      of 21,131 individuals who participated in the U.S. General Social Survey, sexual
      behaviors were the relatively strongest predictors of religious attendance, even
      after controlling for age and gender. Effects of age and gender on religious
      attendance were weaker, and substantially reduced when controlling for sexual and
      family patterns. A sample of 902 college students provided more detailed
      information on religious, moral, and sexual variables. Results suggest that 1)
      moral views about sexual behavior are more strongly linked to religious
      attendance than other moral issues, and 2) mating strategy is more powerful than
      standard personality variables in predicting religious attendance. These findings
      suggest that reproductive strategies are at the heart of variations in religious
      attendance.

PMID- 21874106
TI  - A comprehensive bone-health management approach for men with prostate cancer
      receiving androgen deprivation therapy.
AB  - For advanced and metastatic prostate cancer, androgen deprivation therapy (adt)
      is the mainstay of treatment. Awareness of the potential bone-health
      complications consequent to adt use is increasing. Many studies have shown that
      prolonged adt leads to significant bone loss and increased fracture risk that
      negatively affect quality of life. Clinical practice guidelines for preserving
      bone health in men with prostate cancer on adt vary across Canada. This paper
      reviews recent studies on bone health in men with prostate cancer receiving adt
      and the current evidence regarding bone-health monitoring and management in
      reference to Canadian provincial guidelines. Based on this narrative review, we
      provide general bone-health management recommendations for men with prostate
      cancer receiving adt.

PMID- 21874107
TI  - Triple-negative breast cancers: an updated review on treatment options.
AB  - Morphologic features of tumour cells have long been validated for the clinical
      classification of breast cancers and are regularly used as a "gold standard" to
      ascertain prognostic outcome in patients. Identification of molecular markers
      such as expression of the receptors for estrogen (er) and progesterone (pgr) and
      the human epidermal growth factor receptor 2 (her2) has played an important role
      in determining targets for the development of efficacious drugs for treatment and
      has also offered additional predictive value for the therapeutic assessment of
      patients with breast cancer. More recent technical advancements in identifying
      several cancer-related genes have provided further opportunities to identify
      specific subtypes of breast cancer. Among the subtypes, tumours with triple
      negative cells are identified using specific staining procedures for basal
      markers such as cytokeratin 5 and 6 and the absence of er, pgr, and her2
      expression. Patients with triple-negative breast cancers therefore have the
      disadvantage of not benefiting from currently available receptor-targeted
      systemic therapy. Optimal conditions for the therapeutic assessment of women with
      triple-negative breast tumours and for the management of their disease have yet
      to be validated in prospective investigations. The present review discusses the
      differences between triple-negative breast tumours and basal-like breast tumours
      and also the role of mutations in the BRCA genes. Attention is also paid to
      treatment options available to patients with triple-negative breast tumours.

PMID- 21874108
TI  - Canadian Expert Group consensus recommendations: KRAS testing in colorectal
      cancer.
AB  - Monoclonal antibodies against the epidermal growth factor receptor (anti-egfr)
      when used in the treatment of metastatic colorectal cancer are associated with
      improved survival. Patients whose tumours harbor a KRAS mutation in codon 12 or
      13 have been shown not to benefit from anti-egfr antibodies. The importance of
      KRAS mutation status in the management of patients with metastatic colorectal
      cancer has led to the elaboration of Canadian consensus recommendations on KRAS
      testing, with the aim of standardizing practice across Canada and reconciling
      testing access with the clinical demand for testing. The present guidelines were
      developed at a Canadian consensus meeting held in Montreal in April 2010. The
      best available evidence and expertise were used to develop recommendations for
      various aspects of KRAS testing, including indications and timing for testing,
      sample requirements, recommendations for reporting requirements, and acceptable
      turnaround times.

PMID- 21874109
TI  - cml biology for the clinician in 2011: six impossible things to believe before
      breakfast on the way to cure.
AB  - Chronic myeloid leukemia (cml) is a model disease in oncology: it is the first
      human cancer linked to a distinct chromosomal abnormality, ultimately causing
      constitutive overactivity of a known oncogenic tyrosine kinase that represents a
      drug target. The introduction of the tyrosine kinase inhibitor imatinib into
      clinical practice has far exceeded expectations and resurrected hope that the
      fundamental insights from the "war on cancer" can lead to significant therapeutic
      advances. Nevertheless, the current perception among clinicians is that imatinib
      and its newer more potent cousins offer superb long-term disease control for most
      patients, but that cure without transplantation has remained elusive. However,
      several important laboratory-based observations over the last few years have
      changed those perceptions. Several of those developments are discussed here,
      including direct manipulation of the apoptosis pathway in cancer cells and
      prevention of disease progression with the use of antioxidants. Intriguing
      results from a French study indicate that, if disease progression is halted, a
      small but significant group of patients may be able to stop imatinib therapy
      without disease recurrence. And for patients whose disease, because of resistant
      stem cells, needs a more direct attack than tyrosine kinase inhibitors alone,
      several approaches investigated in laboratory and animal models seem promising,
      and some are ripe for clinical testing, including inhibitors of Smoothened and 5
      lipoxygenase, and suppression of autophagy. Thus, there is realistic hope that
      true cure of cml, without transplantation, may be a feasible goal in the near
      future.

PMID- 21874110
TI  - Prophylactic feeding tubes for patients with locally advanced head-and-neck
      cancer undergoing combined chemotherapy and radiotherapy-systematic review and
      recommendations for clinical practice.
AB  - GOALS: This work aimed to determine the benefits and risks of prophylactic
      feeding tubes for adult patients with squamous cell carcinoma of the head and
      neck who receive combined chemotherapy and radiotherapy with curative intent and
      to make recommendations on the use of prophylactic feeding tubes and the
      provision of adequate nutrition to this patient population. METHODS: A national
      multidisciplinary panel conducted a systematic review of the evidence and
      formulated recommendations to guide clinical decision-making. The draft evidence
      summary and recommendations were distributed to clinicians across Canada for
      their input. MAIN RESULTS: No randomized controlled trials have directly
      addressed this question. Evidence from studies in the target population was
      limited to seven descriptive studies: two with control groups (one prospective,
      one retrospective) and five without control groups. Results from ten controlled
      studies in patients treated with radiotherapy alone were also reviewed.
      CONCLUSIONS: The available evidence was insufficient to draw definitive
      conclusions about the effectiveness of prophylactic feeding tubes in the target
      patient population or to support an evidence-based practice guideline. After
      review of the evidence, of guidelines from other groups, and of current clinical
      practice in Canada, the multidisciplinary panel made consensus-based
      recommendations regarding comprehensive interdisciplinary clinical care before,
      during, and after cancer treatment. The recommendations are based on the expert
      opinion of the panel members and on their understanding of best clinical
      practice.

PMID- 21874111
TI  - Systemic therapy for advanced gastric cancer: a clinical practice guideline.
AB  - QUESTION: What is the optimal chemotherapy regimen in advanced gastric cancer?
      PERSPECTIVES: Gastric cancer is the second leading cause of cancer mortality
      worldwide. Despite low incidence rates for gastric cancer in Ontario, the overall
      prognosis is bleak, with 5-year survival rates of approximately 23% in Canada.
      Even with the considerable body of research available on chemotherapy for
      advanced gastric cancer, uncertainty remains. There is no recognized standard
      treatment, and there appears to be geographic variation in practice. OUTCOMES:
      Outcomes of interest were overall survival, objective response rate (complete
      plus partial responses), time to disease progression, adverse effects, and
      quality of life. METHODOLOGY: After a systematic review, a practice guideline
      containing clinical recommendations relevant to patients in Ontario was drafted.
      The practice guideline was reviewed and approved by the Gastrointestinal Disease
      Site Group (gi dsg) and the Report Approval Panel of the Program in Evidence
      Based Care. External review by Ontario practitioners was obtained through a
      survey, the results of which were incorporated into the practice guideline.
      PRACTICE GUIDELINE: The gi dsg makes the following recommendations: To improve
      survival, a platinum agent should be included in any combination chemotherapy
      regimen.Within a combination chemotherapy regimen, oral capecitabine is preferred
      over intravenous 5-fluorouracil (5fu)-that is, epirubicin-cisplatin-capecitabine
      is preferred over the prior standard regimen, epirubicin-cisplatin-5fu
      (ecf).Epirubicin-oxaliplatin-capecitabine (eox) is a reasonable alternative to
      ecf. The choice between ecf and eox should be based on patient
      preference.Trastuzumab in combination with cisplatin and a fluoropyrimidine (5fu
      or oral capecitabine) is recommended for advanced gastric cancer positive for the
      human epidermal growth factor receptor 2 (her2/neu).

PMID- 21874112
TI  - Triple-negative and basal-like breast cancer: implications for oncologists.

PMID- 21874113
TI  - Consensus-based nutritional recommendations for patients with head-and-neck
      cancer.

PMID- 21874114
TI  - Kissing: hullo hpv.

PMID- 21874115
TI  - E-manuscript article summaries.

PMID- 21874116
TI  - Shaping policy: the Canadian Cancer Society and the Hormone Receptor Testing
      Inquiry.
AB  - BACKGROUND: In 2007, the Government of Newfoundland and Labrador established the
      Commission of Inquiry on Hormone Receptor Testing to examine problems with
      estrogen and progesterone hormone receptor tests conducted in the province
      between 1997 and 2005. Using the Inquiry as a case study, we examine the
      knowledge transfer activities used by the Canadian Cancer Society - Newfoundland
      and Labrador Division (CCS-NL) to shape policy and improve cancer control in the
      province. IMPLEMENTATION: CCS-NL established a panel to advise its legal counsel
      and asked academic researchers to prepare papers to submit to the Commission. CCS
      NL also interviewed patients to better inform its legal arguments, used its
      province-wide networks to raise awareness of the Inquiry, and provided a toll
      free number that people could call. It also provided basic information,
      resources, and contact information for people who were affected by the flawed
      hormone receptor tests. The effectiveness of CCS-NL's activities is reflected by
      the inclusion of its key messages in the Commission's recommendations, and the
      investment in cancer care following the Inquiry. DISCUSSION: The success of the
      CCS-NL knowledge transfer efforts stemmed from its reputation as an advocate for
      cancer patients and its long-standing relationship with researchers, especially
      at the local level. The case illustrates real-world application of knowledge
      transfer practices in the development of public policy, and describes how
      community-based non-government organizations can identify and draw attention to
      important issues that otherwise might not have been addressed.

PMID- 21874117
TI  - Emerging trends in the treatment of triple-negative breast cancer in Canada: a
      survey.
AB  - Triple-negative breast cancer (TNBC) has a poor prognosis compared to other
      subtypes and lacks common therapeutic targets, including HER 2 and the estrogen
      and progesterone receptors. The clinicopathological heterogeneity of the disease
      and limited treatment options make clinical management particularly challenging.
      Here we present the results of a survey of Canadian clinical oncologists
      regarding treatment of TNBC, and review recent and ongoing clinical research in
      this area. Our survey results show that the majority of respondents use a
      combination of anthracyclines-taxanes as adjuvant therapy for early TNBC. For the
      first-line treatment of metastatic TNBC, most clinicians recommend taxanes, while
      single agent capecitabine and platinum-based therapies are more common for
      subsequent lines of therapy. Despite the ongoing development of novel targeted
      therapies, chemotherapy remains the mainstay of treatment for TNBC.

PMID- 21874118
TI  - A single-centre chart review exploring the adjusted association between breast
      cancer phenotype and prognosis.
AB  - PURPOSE AND METHODS: Using a retrospective chart review, we investigated the
      differences in survival and prognostic factors between patients with triple
      negative breast cancer (tnbc) and those with non-tnbc. The review included 1018
      breast cancer patients who were diagnosed between 2000 and 2005 in Essex, Kent,
      and Lambton counties in Ontario, Canada. RESULTS: Our findings indicate that,
      although the unadjusted results suggested that patients with tnbc were more
      likely than patients with non-tnbc to die [hazard ratio (hr): 2.29; 95%
      confidence interval (ci): 1.33 to 2.93], an adjusted survival analysis revealed
      no significant difference in overall survival between the groups (hr: 1.22; 95%
      ci: 0.63 to 2.39). The significant predictors of survival in the adjusted
      analysis were age, stage of cancer, and size of cancer. CONCLUSIONS: Our findings
      support those of earlier reports, which suggest that presenting tumour size is
      the most important prognostic factor in tnbc. Investigations into unique
      screening methods to identify these tumours at an earlier stage and to prevent
      advanced-stage cancer in this patient subpopulation are necessary.

PMID- 21874119
TI  - Shaping the Genome with Non-Coding RNAs.
AB  - The human genome must be tightly packaged in order to fit inside the nucleus of a
      cell. Genome organization is functional rather than random, which allows for the
      proper execution of gene expression programs and other biological processes.
      Recently, three-dimensional chromatin organization has emerged as an important
      transcriptional control mechanism. For example, enhancers were shown to regulate
      target genes by physically interacting with them regardless of their linear
      distance and even if located on different chromosomes. These chromatin contacts
      can be measured with the "chromosome conformation capture" (3C) technology and
      other 3C-related techniques. Given the recent innovation of 3C-derived
      approaches, it is not surprising that we still know very little about the
      structure of our genome at high-resolution. Even less well understood is whether
      there exist distinct types of chromatin contacts and importantly, what regulates
      them. A new form of regulation involving the expression of long non-coding RNAs
      (lncRNAs) was recently identified. lncRNAs are a very abundant class of non
      coding RNAs that are often expressed in a tissue-specific manner. Although their
      different subcellular localizations point to their involvement in numerous
      cellular processes, it is clear that lncRNAs play an important role in regulating
      gene expression. How they control transcription however is mostly unknown. In
      this review, we provide an overview of known lncRNA transcription regulation
      activities. We also discuss potential mechanisms by which ncRNAs might exert
      three-dimensional transcriptional control and what recent studies have revealed
      about their role in shaping our genome.

PMID- 21874120
TI  - Forecasting sex differences in mortality in high income nations: The contribution
      of smoking.
AB  - To address the question of whether sex differences in mortality will in the
      future rise, fall, or stay the same, this study uses relative smoking prevalence
      among males and females to forecast future changes in relative smoking-attributed
      mortality. Data on 21 high income nations from 1975 to 2000 and a lag between
      smoking prevalence and mortality allow forecasts up to 2020. Averaged across
      nations, the results for logged male/female ratios in smoking mortality reveal
      equalization of the sex differential. However, continued divergence in non
      smoking mortality rates would counter convergence in smoking mortality rates and
      lead to future increases in the female advantage overall, particularly in nations
      at late stages of the cigarette epidemic (such as the United States and the
      United Kingdom).

PMID- 21874121
TI  - Flesh Poems: Henry Tonks and the Art of Surgery.

PMID- 21874122
TI  - Integrating Palliative Care in the ICU: The Nurse in a Leading Role.
AB  - Palliative care is increasingly recognized as an integral component of
      comprehensive intensive care for all critically ill patients, regardless of
      prognosis, and for their families. Here we discuss the key role that nurses can
      and must continue to play in making this evidence-based paradigm a clinical
      reality across a broad range of ICUs. We review the contributions of nurses to
      implementation of ICU safety initiatives as a model that can be applied to ICU
      palliative care integration. We focus on the importance of nursing involvement in
      design and application of work processes that facilitate this integration in a
      systematic way, including processes that ensure the participation of nurses in
      discussions and decision making with families about care goals. We suggest ways
      that nurses can help to operationalize an integrated approach to palliative care
      in the ICU and to define their own essential role in a successful, sustainable
      ICU palliative care improvement effort. Finally, we identify resources including
      The IPAL-ICU ProjectTM, a new initiative by the Center to Advance Palliative Care
      that can assist nurses and other healthcare professionals to move such efforts
      forward in diverse critical care settings.

PMID- 21874123
TI  - SUPPORTING PHYSICIANS' PRACTICE-BASED LEARNING AND IMPROVEMENT (PBLI) AND QUALITY
      IMPROVEMENT THROUGH EXPLORATION OF POPULATION-BASED MEDICAL DATA.
AB  - Participating in self-assessment activities may stimulate improvement in practice
      behaviors. However, it is unclear how best to support the development of self
      assessment skills, particularly in the health care domain. Exploration of
      population-based data is one method to enable health care providers to identify
      deficiencies in overall practice behavior that can motivate quality improvement
      initiatives. At the University of Virginia, we are developing a decision support
      tool to integrate and present population-based patient data to health care
      providers related to both clinical outcomes and non-clinical measures (e.g.,
      demographic information). By enabling users to separate their direct impact on
      clinical outcomes from other factors out of their control, we may enhance the
      self-assessment process.

PMID- 21874124
TI  - Position Control of Motion Compensation Cardiac Catheters.
AB  - Robotic catheters have the potential to revolutionize cardiac surgery by enabling
      minimally invasive structural repairs within the beating heart. This paper
      presents an actuated catheter system that compensates for the fast motion of
      cardiac tissue using 3D ultrasound image guidance. We describe the design and
      operation of the mechanical drive system and catheter module and analyze the
      catheter performance limitations of friction and backlash in detail. To mitigate
      these limitations, we propose and evaluate mechanical and control system
      compensation methods, including inverse and model-based backlash compensation, to
      improve the system performance. Finally, in vivo results are presented that
      demonstrate that the catheter can track the cardiac tissue motion with less than
      1 mm RMS error. The ultimate goal of this research is to create a fast and
      dexterous robotic catheter system that can perform surgery on the delicate
      structures inside of the beating heart.

PMID- 21874125
TI  - Commentary on 'Selective serotonin reuptake inhibitors (SSRIs) for autism
      spectrum disorders (ASD)'

PMID- 21874126
TI  - Impressions of Danger Influence Impressions of People: An Evolutionary
      Perspective on Individual and Collective Cognition.
AB  - An evolutionary approach to social cognition yields novel hypotheses about the
      perception of people belonging to specific kinds of social categories. These
      implications are illustrated by empirical results linking the perceived threat of
      physical injury to stereotypical impressions of outgroups. We review a set of
      studies revealing several ways in which threat-connoting cues influence
      perceptions of ethnic outgroups and the individuals who belong to those
      outgroups. We also present new results that suggest additional implications of
      evolved danger-avoidance mechanisms on interpersonal communication and the
      persistence of cultural-level stereotypes about ethnic outgroups. The conceptual
      utility of an evolutionary approach is further illustrated by a parallel line of
      research linking the threat of disease to additional kinds of social perceptions
      and behaviors. Evolved danger-avoidance mechanisms appear to contribute in
      diverse ways to individual-level cognitive processes, as well as to culturally
      shared collective beliefs.

PMID- 21874127
TI  - Science, interdisciplinarity, and the society.

PMID- 21874128
TI  - What is a problem?: On problem-oriented interdisciplinarity.
AB  - Among others, the term "problem" plays a major role in the various attempts to
      characterize interdisciplinarity or transdisciplinarity, as used synonymously in
      this paper. Interdisciplinarity (ID) is regarded as "problem solving among
      science, technology and society" and as "problem orientation beyond disciplinary
      constraints" (cf. Frodeman et al.: The Oxford Handbook of Interdisciplinarity.
      Oxford University Press, Oxford, 2010). The point of departure of this paper is
      that the discourse and practice of ID have problems with the "problem". The
      objective here is to shed some light on the vague notion of "problem" in order to
      advocate a specific type of interdisciplinarity: problem-oriented
      interdisciplinarity. The outline is as follows: Taking an ex negativo approach, I
      will show what problem-oriented ID does not mean. Using references to well
      established distinctions in philosophy of science, I will show three other types
      of ID that should not be placed under the umbrella term "problem-oriented ID":
      object-oriented ID ("ontology"), theory-oriented ID (epistemology), and method
      oriented ID (methodology). Different philosophical thought traditions can be
      related to these distinguishable meanings. I will then clarify the notion of
      "problem" by looking at three systematic elements: an undesired (initial) state,
      a desired (goal) state, and the barriers in getting from the one to the other.
      These three elements include three related kinds of knowledge: systems, target,
      and transformation knowledge. This paper elaborates further methodological and
      epistemological elements of problem-oriented ID. It concludes by stressing that
      problem-oriented ID is the most needed as well as the most challenging type of
      ID.

PMID- 21874129
TI  - Interdisciplinarity and innovation dynamics. On convergence of research,
      technology, economy, and society.
AB  - In the age of globalization, economic growth and the welfare of nations
      decisively depend on basic innovations. Therefore, education and knowledge is an
      important advantage of competition in highly developed countries with high
      standards of salaries, but raw material shortage. In the twenty-first century,
      innovations will arise from problem-oriented research, crossing over traditional
      faculties and disciplines. Therefore, we need platforms of interdisciplinary
      dialogue to choose transdisciplinary problems (e.g., environment, energy,
      information, health, welfare) and to cluster new portfolios of technologies. The
      clusters of research during the excellence initiative at German universities are
      examples of converging sciences. The integration of natural and engineering
      sciences as well as medicine can only be realized if the research training
      programs (e.g., graduate schools) generate a considerable added value in terms of
      multidisciplinary experience, international networking, scientific and
      entrepreneurial know-how, and personality development. The Carl von Linde-Academy
      is presented as an example of an interdisciplinary center of research and
      teaching at the Technical University of Munich.

PMID- 21874130
TI  - A critique of Bernstein's beyond objectivism and relativism: science,
      hermeneutics, and praxis.
AB  - This analysis comments on Bernstein's lack of clear understanding of
      subjectivity, based on his book, Beyond Objectivism and Relativism: Science,
      Hermeneutics, and Praxis. Bernstein limits his interpretation of subjectivity to
      thinkers such as Gadamer and Habermas. The authors analyze the ideas of classic
      scholars such as Edmund Husserl and Friedrich Nietzsche. Husserl put forward his
      notion of transcendental subjectivity and phenomenological ramifications of the
      relationship between subjectivity and objectivity. Nietzsche referred to
      subjectivity as "perspectivism," the inescapable fact that any and all
      consciousnesses exist in space and time. Consciousness is fundamentally
      constituted of cultural, linguistic, and historical dimensions.

PMID- 21874131
TI  - Surgical management of pilon fractures with large segmental bone defects using
      fibular strut allografts: a report of two cases.
AB  - We present two patients with open pilon fractures with large bone defects treated
      successfully with fibular strut allografts. The patients were initially treated
      by massive irrigation, wound debridement, and temporary external fixation. After
      complete wound healing, the bone defects were managed. Because autologous iliac
      crest or fibular bone grafts were impossible to be harvested due to multiple
      fractures, the bone defects were reconstructed with fibular strut allografts.
      Fixation was performed with a periarticular distal tibia locking plate. At 2
      months postoperatively, the patients ambulated with partial weight-bearing; at 6
      months, they had full range of motion of the ankle joint and full weight-bearing.

PMID- 21874132
TI  - A model of the influence of false-positive mammography screening results on
      subsequent screening.
AB  - Decades of empirical research have demonstrated psychological and behavioural
      consequences of false-positive medical tests. To organise this literature and
      offer novel predictions, we propose a model of how false-positive mammography
      results affect return for subsequent mammography screening. We propose that false
      positive mammography results alter how women think about themselves (e.g.,
      increasing their perceived likelihood of getting breast cancer) and the screening
      test (e.g., believing mammography test results are less accurate). We further
      hypothesise that thoughts elicited by the false-positive experience will, in
      turn, affect future use of screening mammography. In addition, we discuss
      methodological considerations for statistical analyses of these mediational
      pathways and propose two classes of potential moderators. While our model focuses
      on mammography screening, it may be applicable to psychological and behavioural
      responses to other screening tests. The model is especially timely as false
      positive medical test results are increasingly common, due to efforts to increase
      uptake of cancer screening, new technologies that improve existing tests' ability
      to detect disease at the cost of increased false alarms, and growing numbers of
      new medical tests.

PMID- 21874133
TI  - Renovating the Pyramid of Needs: Contemporary Extensions Built Upon Ancient
      Foundations.
AB  - Maslow's pyramid of human needs, proposed in 1943, has been one of the most
      cognitively contagious ideas in the behavioral sciences. Anticipating later
      evolutionary views of human motivation and cognition, Maslow viewed human motives
      as based in innate and universal predispositions. We revisit the idea of a
      motivational hierarchy in light of theoretical developments at the interface of
      evolutionary biology, anthropology, and psychology. After considering motives at
      three different levels of analysis, we argue that the basic foundational
      structure of the pyramid is worth preserving, but that it should be buttressed
      with a few architectural extensions. By adding a contemporary design feature,
      connections between fundamental motives and immediate situational threats and
      opportunities should be highlighted. By incorporating a classical element, these
      connections can be strengthened by anchoring the hierarchy of human motives more
      firmly in the bedrock of modern evolutionary theory. We propose a renovated
      hierarchy of fundamental motives that serves as both an integrative framework and
      a generative foundation for future empirical research. 

PMID- 21874134
TI  - When Adaptations Go Awry: Functional and Dysfunctional Aspects of Social Anxiety.
AB  - Adaptations are psychological and behavioral mechanisms designed through
      evolution to serve specific purposes ultimately related to reproductive success.
      Although adaptations are inherently functional, in some cases their operation can
      nevertheless cause personal and social dysfunction. We describe a theoretical
      framework for understanding, predicting, and reducing the dysfunctional
      consequences of psychological adaptations. We discuss three general sources of
      dysfunction: a) the existence of adaptive tradeoffs, b) mismatches between
      current environments and ancestral environments, and c) individual differences.
      The paper applies this framework primarily to the topic of social anxiety, a
      psychological phenomenon marked by concerns pertaining to social rejection and
      embarrassment. Although social anxiety can serve useful functions, it can also
      involve excessive worry, negative affect, and avoidance of social situations,
      leading to significant distress and social impairment. We consider sources of
      dysfunction in social anxiety and discuss implications for policy, including
      recommendations for psychological, situational, and biological interventions. We
      also discuss broader applications of this theoretical framework to other areas of
      social life.

PMID- 21874135
TI  - The value of transnational medical research.

PMID- 21874136
TI  - Will He Be There?: Mediating malaria, immobilizing science.
AB  - This paper focuses on an unsettling example of experimental labour - the Human
      Landing Catch (HLC). The HLC is a cheap and reliable technique to produce data on
      mosquito densities in a defined area. It requires only a human volunteer to sit
      over night with his legs exposed, a headlamp to spot mosquitoes, and a rubber
      tube and plastic cup to catch them as they come to feed on him. The HLC formed
      the central methodological and operational strategy for a malaria control that
      took place in Dar es Salaam, funded by the Bill and Melinda Gates Foundation.
      This paper analyses the epistemic and economic value of this experimental
      scenario by examining in detail the work it entails. In conceptualizing the
      different species of productivity associated with the HLC, of particular interest
      is the surprising fact that he is there. This paper argues that the interplay of
      mobility and immobility offers a way to rethink the value of research within
      interlocking circulations of capital, science, mosquitoes and men.

PMID- 21874137
TI  - Both "illness and temptation of the enemy": melancholy, the medieval patient and
      the writings of King Duarte of Portugal (r. 1433-38).
AB  - Recent historians have rehabilitated King Duarte of Portugal, previously maligned
      and neglected, as an astute ruler and philosopher. There is still a tendency,
      however, to view Duarte as a depressive or a hypochondriac, due to his own
      description of his melancholy in his advice book, the Loyal Counselor. This paper
      reassesses Duarte's writings, drawing on key approaches in the history of
      medicine, such as narrative medicine and the history of the patient. It is
      important to take Duarte's views on his condition seriously, placing them in the
      medical and theological contexts of his time and avoiding modern retrospective
      diagnosis. Duarte's writings can be used to explore the impact of plague, doubt
      and death on the life of a well-educated and conscientious late-medieval ruler.

PMID- 21874138
TI  - Lower cranial nerve palsy, aseptic meningitis and hydrocephalus: unusual
      presentation of primary antiphospholipid syndrome.
AB  - Presentation of primary antiphospholipid syndrome (APS) is usually untrustworthy
      and unusual presentations are difficult to diagnose on the basis of clinical
      features alone. This is true especially in young and elderly patients. Cerebral
      venous thrombosis (CVT) is less frequent than arterial thrombosis in APS. CVT has
      a wide spectrum of signs and symptoms, which may evolve suddenly or over weeks.
      It mimics many neurological conditions such as meningitis, encephalopathy, benign
      intracranial hypertension and stroke. Headache is the most frequent symptom in
      patients with CVT, and is present in about 80% of cases. The most common pattern
      of presentation is with a benign intracranial hypertension-like syndrome. Sixth
      cranial nerve palsy usually manifests as a false localising sign. Patients may
      have recurrent seizures. Cranial nerve syndromes are seen with venous sinus
      thrombosis. We present a case of APS with lower cranial nerve palsy, aseptic
      meningitis and hydrocephalus initially treated as tuberculous meningitis.

PMID- 21874139
TI  - An unusual case of extreme hypernatraemia.
AB  - A 4-year-old severely disabled boy with a congenital myopathy developed profuse
      diarrhoea with hypernatraemia (plasma Na 157 mmol/l). The initial blood urea,
      serum creatinine and urine output were within normal limits. Despite corrective
      measures within a hospital setting, the patient's serum sodium peaked at 202
      mmol/l. A high fractional excretion of sodium (FE Na) in the context of
      dehydration and normal renal function was suggestive of a high sodium load.
      Subsequent investigations revealed an unusual combination of valproate-induced
      Fanconi syndrome, nephrogenic diabetes insipidus and excess sodium load. The case
      illustrates why severe hypernatraemia in children is such a diagnostic challenge.

PMID- 21874140
TI  - Not every cough in bronchiolitis season is bronchiolitis.
AB  - A 2-month-old male infant presented to hospital for the third time in late autumn
      with a 4 week history of cough and respiratory distress. He had presented to
      hospital on two occasions during the previous two weeks, and had twice been
      discharged with a diagnosis of bronchiolitis, based on clinical findings and the
      season. That the nasopharyngeal aspirate (NPA) was negative for respiratory
      viruses did not alter the diagnosis as this was felt to be a common false
      negative finding. However his cough worsened and on his third presentation he had
      respiratory distress with bilateral crackles and wheeze. The C reactive protein
      was 121 mg/l but the NPA was again negative for viruses. He was investigated for
      atypical causes of lower respiratory tract infection and the NPA was positive for
      Chlamydia trachomatis by polymerase chain reaction. He was treated with a 5 day
      course of azithromycin and made a full recovery.

PMID- 21874141
TI  - A woman with muscles pain, weakness, and macular rash.

PMID- 21874142
TI  - Cerebral abscess as a complication of a halo fixation device.

PMID- 21874143
TI  - Haemoperitoneum secondary to rupture of an omental artery aneurysm.

PMID- 21874144
TI  - Reversible iatrogenic subacute cerebellar syndrome, myoclonus and MRI findings
      following metronidazole administration.

PMID- 21874145
TI  - Assessing pain in preterm infants in the neonatal intensive care unit: moving to
      a 'brain-oriented' approach.
AB  - Preterm infants in the neonatal intensive care unit undergo repeated exposure to
      procedural and ongoing pain. Early and long-term changes in pain processing,
      stress-response systems and development may result from cumulative early pain
      exposure. So that appropriate treatment can be given, accurate assessment of pain
      is vital, but is also complex because these infants' responses may differ from
      those of full-term infants. A variety of uni- and multidimensional assessment
      tools are available; however, many have incomplete psychometric testing and may
      not incorporate developmentally important cues. Near-infrared spectroscopy and/or
      EEG techniques that measure neonatal pain responses at a cortical level offer new
      opportunities to validate neonatal pain assessment tools.

PMID- 21874147
TI  - Robotics for Pelvic Reconstruction.
AB  - Robotic-assisted laparoscopy is increasingly used in female pelvic reconstructive
      surgery to combine the benefits of abdominally placed mesh for prolapse outcomes
      with the quicker recovery time associated with minimally invasive procedures.
      Level III data suggest that early outcomes of robotic sacrocolpopexy are similar
      to those of open sacrocolpopexy. A single randomized trial has provided level I
      evidence that robotic and laparoscopic approaches to sacrocolpopexy have similar
      short-term anatomic outcomes, although operating times, postoperative pain, and
      cost are increased with robotics. Patient satisfaction and long-term outcomes of
      both robotic and laparoscopic sacrocolpopexy are insufficiently studied despite
      their widespread use in the treatment of prolapse. Given the high reoperative
      rates for prolapse repairs, long-term follow-up is essential, and well-designed
      comparative effectiveness research is needed to evaluate pelvic floor surgery
      adequately.

PMID- 21874148
TI  - Not Just a Walk in the Park: Methodological Improvements for Determining
      Environmental Justice Implications of Park Access in New York City for the
      Promotion of Physical Activity.
AB  - The purpose of this study is to test the hypothesis that access to parks in New
      York City is not equitable across racial and ethnic categories. It builds on
      previous research that has linked access to parks and open space with increased
      physical activity, which in turn may reduce the risk for adverse health outcomes
      related to obesity. Systematic patterns of uneven access to parks might help to
      explain disparities in these health outcomes across sociodemographic populations
      that are not fully explained by individual-level risk factors and health
      behaviors, and therefore access to parks becomes an environmental justice issue.
      This study is designed to shed light on the "unpatterned inequities" of park
      distributions identified in previous studies of New York City park access. It
      uses a combination of network analysis and a cadastral-based expert dasymetric
      system (CEDS) to estimate the racial/ethnic composition of populations within a
      reasonable walking distance of 400m from parks. The distance to the closest park,
      number of parks within walking distance, amount of accessible park space, and
      number of physical activity sites are then evaluated across racial/ethnic
      categories, and are compared to the citywide populations using odds ratios. The
      odds ratios revealed patterns that at first glance appear to contradict the
      notion of distributional inequities. However, discussion of the results points to
      the need for reassessing what is meant by "access" to more thoroughly consider
      the aspects of parks that are most likely to contribute to physical activity and
      positive health outcomes.

PMID- 21874146
TI  - Drug-induced Liver Injury.
AB  - Drug-induced liver injury (DILI) is common and nearly all classes of medications
      can cause liver disease. Most cases of DILI are benign, and improve after drug
      withdrawal. It is important to recognize and remove the offending agent as
      quickly as possible to prevent the progression to chronic liver disease and/or
      acute liver failure. There are no definite risk factors for DILI, but pre
      existing liver disease and genetic susceptibility may predispose certain
      individuals. Although most patients have clinical symptoms that are identical to
      other liver diseases, some patients may present with symptoms of systemic
      hypersensitivity. Treatment of drug and herbal-induced liver injury consists of
      rapid drug discontinuation and supportive care targeted to alleviate unwanted
      symptoms.

PMID- 21874149
TI  - Promoting Active Urban Aging: A Measurement Approach to Neighborhood Walkability
      for Older Adults.
AB  - Understanding the role of the built environment on physical activity behavior
      among older adults is an important public health goal, but evaluating these
      relationships remains complicated due to the difficulty of measuring specific
      attributes of the environment. As a result, there is conflicting evidence
      regarding the association between perceived and objectively measured walkability
      and physical activity among urban-dwelling older adults. This suggests that both
      actual environmental features and perceptions of these attributes influence
      walking behavior. The purpose of this pilot project is to create an Objective
      Walkability Index (OWI) by census block using a Geographic Information System
      (GIS) and supplement the results with resident perceptions thus more accurately
      characterizing the context of walkability. Computerized Neighborhood Environment
      Tracking (ComNET) was used to systematically assess environmental risks impacting
      activity patterns of older adults in two New York City neighborhoods. In
      addition, the Senior Center Evaluation of the Neighborhood Environment (SCENE)
      survey was administered to older adults attending two senior centers located
      within the target neighborhoods. The results indicate that there is substantial
      variation in OWI score both between and within the neighborhoods suggesting that
      residence in some communities may increase the risk of inactivity among older
      adults. Also, low walkability census blocks were clustered within each
      neighborhood providing an opportunity for targeted investigation into localized
      threats to walkability. A lack of consensus regarding the association between the
      built environment and physical activity among older adults is a consequence of
      the problems inherent in measuring these determinants. Further empirical evidence
      evaluating the complex relationships between the built environment and physical
      activity is an essential step towards creating active communities.

PMID- 21874150
TI  - Community Gardens: An Exploration of Urban Agriculture in the Bronx, New York
      City.

PMID- 21874151
TI  - Influences of observer sex, facial masculinity, and gender role identification on
      first impressions of men's faces.
AB  - Evaluations of male faces depend on attributes of the observer and target and may
      influence future social and sexual decisions. However, it is unknown whether
      adherence to hypertraditional gender roles may shape women's evaluations of
      potential sexual partners or men's evaluations of potential competitors. Using a
      photo task, we tested participants' judgments of attractiveness, trustworthiness,
      aggressiveness, and masculinity of male faces altered to appear more masculine or
      feminine. Findings revealed that higher hypermasculinity scores in male observers
      were correlated with higher attractiveness and trustworthiness ratings of the
      male faces; conversely, higher hyperfemininity scores in female observers were
      associated with lower ratings on those traits. Male observers also rated the
      faces as more aggressive than did female observers. Regarding ratings by face
      type, masculinized faces were rated more aggressive than feminized faces, and
      women's ratings did not discriminate between altered faces better than men's
      ratings. These results suggest that first impressions of men can be explained in
      part by socioculturally- and evolutionarily-relevant factors such as the
      observer's sex and gender role adherence, as well as the target's facial
      masculinity.

PMID- 21874152
TI  - More Memory Bang for the Attentional Buck: Self-Protection Goals Enhance Encoding
      Efficiency for Potentially Threatening Males.
AB  - When encountering individuals with a potential inclination to harm them, people
      face a dilemma: Staring at them provides useful information about their
      intentions but may also be perceived by them as intrusive and challenging-thereby
      increasing the likelihood of the very threat the people fear. One solution to
      this dilemma would be an enhanced ability to efficiently encode such individuals
      to be able to remember them without spending any additional direct attention on
      them. In two experiments, the authors primed self-protective concerns in
      perceivers and assessed visual attention and recognition memory for a variety of
      faces. Consistent with hypotheses, self-protective participants (relative to
      control participants) exhibited enhanced encoding efficiency (i.e., greater
      memory not predicated on any enhancement of visual attention) for Black and Arab
      male faces-groups stereotyped as being potentially dangerous-but not for female
      or White male faces. Results suggest that encoding efficiency depends on the
      functional relevance of the social information people encounter.

PMID- 21874153
TI  - Effect of Inhibiting Histone Deacetylase with Short-Chain Carboxylic Acids and
      Their Hydroxamic Acid Analogs on Vertebrate Development and Neuronal Chromatin.
AB  - Carboxylic acids with known central nervous system and histone deacetylase (HDAC)
      inhibitory activities were converted to hydroxamic acids and tested using a suite
      of in vitro biochemical assays with recombinant HDAC isoforms, cell based assays
      in human cervical carcinoma Hela cells and primary cultures from mouse forebrain,
      and a whole animal (Xenopus laevis) developmental assay. Relative to the parent
      carboxylic acids, two of these analogs exhibited enhanced potency, and one analog
      showed altered HDAC isoform selectivity and in vivo activity in the Xenopus
      assay. We discuss potential uses of these novel hydroxamic acids in studies aimed
      at determining the utility of HDAC inhibitors as memory enhancers and mood
      stabilizers.

PMID- 21874154
TI  - PREVENCION DEL VIH/SIDA EN LOS CIRCUITOS DE LEVANTE HSH: UNA ASIGNATURA
      PENDIENTE.
AB  - A partir de un relevamiento de tipo etnografico, se describen lugares de
      encuentro de HSH en la Ciudad de Buenos Aires y sus practicas sexuales. El
      reconocimiento de tales espacios, asi como las caracteristicas que asumen en
      ellos los encuentros sexuales entre los HSH, plantean obstaculos especificos en
      la adopcion de comportamientos preventivos y, asimismo, generan nuevos desafios
      para las actividades de prevencion. Se plantean las dificultades y debates
      conceptuales que la misma categoria presenta, y sus consecuencias en el abordaje
      preventivo y teorico-metodologico para las ciencias sociales. Ademas, se proponen
      nuevos interrogantes acerca de los alcances y las limitaciones del modelo
      preventivo del VIH/Sida para HSH.

PMID- 21874155
TI  - Expanding the pleuromutilin class of antibiotics by de novo chemical synthesis.
AB  - New pleuromutilin-like compounds were synthesized in approximately 11 steps from
      3-allylcyclopent-2-enone by a strategy featuring sequential carbonyl addition
      reactions. Several analogs possessing the C14 tiamulin ester side chain displayed
      activity in a Mycobacterium tuberculosis mc(2)7000 assay. The results described
      herein provide a basis for further efforts to expand the structural and
      stereochemical diversity of the pleuromutilin class of bacterial protein
      synthesis inhibitors through advances in chemical synthesis.

PMID- 21874156
TI  - Platelet Activation Following Exposure to Anti-ABO Antibodies-An In Vitro Study.
AB  - Since platelets possess A and B antigen, mismatched ABO platelets could,
      theoretically, become activated or hypofunctional by exposure to anti-A or anti-B
      antibodies found in transfused or recipient plasma. Following normal baseline
      platelet aggregation to adenosine diphosphate (ADP), platelets from normal donors
      of different blood types were incubated at 37 degrees C for 10 minutes with 50MUl
      of normal saline (NS), O plasma, or AB plasma. Aggregation was then induced with
      ADP. No significant changes from baseline were seen in platelet aggregation
      studies following incubation with NS. However, platelet aggregations of type A
      and type B platelets were significantly inhibited when incubated with O plasma
      (mean of 41 and 22%, respectively). Our findings indicate that mediators in group
      O plasma, very likely anti-A and anti-B antibodies, cause impaired platelet
      aggregation of ABO non-identical platelets.

PMID- 21874157
TI  - Functional classification of pulmonary hypertension in children: Report from the
      PVRI pediatric taskforce, Panama 2011.
AB  - The members of the Pediatric Task Force of the Pulmonary Vascular Research
      Institute (PVRI) were aware of the need to develop a functional classification of
      pulmonary hypertension in children. The proposed classification follows the same
      pattern and uses the same criteria as the Dana Point pulmonary hypertension
      specific classification for adults. Modifications were necessary for children,
      since age, physical growth and maturation influences the way in which the
      functional effects of a disease are expressed. It is essential to encapsulate a
      child's clinical status, to make it possible to review progress with time as
      he/she grows up, as consistently and as objectively as possible. Particularly in
      younger children we sought to include objective indicators such as thriving, need
      for supplemental feeds and the record of school or nursery attendance. This helps
      monitor the clinical course of events and response to treatment over the years.
      It also facilitates the development of treatment algorithms for children. We
      present a consensus paper on a functional classification system for children with
      pulmonary hypertension, discussed at the Annual Meeting of the PVRI in Panama
      City, February 2011.

PMID- 21874159
TI  - Endogenously EGFP-Labeled Mouse Embryonic Stem Cells.
AB  - Transplantation of embryonic stem cell (ESC)-derived precursors holds great
      promise for treating various disease conditions. Tracing of precursors derived
      from ESC after transplantation is important to determine their migration and
      fate. Chemical labeling, as well as transfection or viral-mediated transduction
      of tracer genes in ESC or in ESC-derived precursors, which are the methods that
      have been used in the generation of the vast majority of labeled ESCs, have
      serious drawbacks such as varying efficacy. To circumvent this problem we
      generated endogenously traceable mouse (m)ESC clones by direct derivation from
      blastocysts of transgenic mice expressing enhanced green fluorescent protein
      (EGFP) under control of the housekeeping beta-actin promoter The only previous
      report of endogenously EGFP-labeled mESC derived directly from transgenic EGFP
      embryos is that of Ahn and colleagues (Ahn et al, 2008. Cytotherapy 10:759-769),
      who used embryos from a different transgenic line and used a significantly
      different protocol for derivation. Cells from a high-expressing EGFP-mESC clone,
      G11, retain high levels of EGFP expression after differentiation into derivatives
      of all three primary germ layers both in vitro and in vivo, and contribution to
      all tissues in chimeric progeny. To determine whether progenitor cells derived
      from G11 could be used in transplantation experiments, we differentiated them to
      early neuronal precursors and injected them into syngeneic mouse brains.
      Transplanted EGFP-expressing cells at different stages of differentiation along
      the neuronal lineage could be identified in brains by expression of EGFP twelve
      weeks after transplantation. Our results suggest that the EGFP-mESC(G11) line may
      constitute a useful tool in ESC-based cell and tissue replacement studies.

PMID- 21874158
TI  - A consensus approach to the classification of pediatric pulmonary hypertensive
      vascular disease: Report from the PVRI Pediatric Taskforce, Panama 2011.
AB  - Current classifications of pulmonary hypertension have contributed a great deal
      to our understanding of pulmonary vascular disease, facilitated drug trials, and
      improved our understanding of congenital heart disease in adult survivors.
      However, these classifications are not applicable readily to pediatric disease.
      The classification system that we propose is based firmly in clinical practice.
      The specific aims of this new system are to improve diagnostic strategies, to
      promote appropriate clinical investigation, to improve our understanding of
      disease pathogenesis, physiology and epidemiology, and to guide the development
      of human disease models in laboratory and animal studies. It should be also an
      educational resource. We emphasize the concepts of perinatal maladaptation,
      maldevelopment and pulmonary hypoplasia as causative factors in pediatric
      pulmonary hypertension. We highlight the importance of genetic, chromosomal and
      multiple congenital malformation syndromes in the presentation of pediatric
      pulmonary hypertension. We divide pediatric pulmonary hypertensive vascular
      disease into 10 broad categories.

PMID- 21874160
TI  - Ethnic Minority Children's Active Commuting to School and Association with
      Physical Activity and Pedestrian Safety Behaviors.
AB  - BACKGROUND: Children's active commuting to school, i.e. walking or cycling to
      school, was associated with greater moderate-to-vigorous physical activity,
      although studies among ethnic minorities are sparse. OBJECTIVES: Among a low
      income, ethnic minority sample of fourth grade students from eight public
      schools, we examined (1) correlates of active commuting to school and (2) the
      relationship between active commuting to school and moderate-to-vigorous physical
      activity. METHODS: We conducted a cross-sectional analysis of baseline
      measurements from a sample of participants (n=149) aged 9-12 years from a walk to
      school intervention study in Houston, Texas. The primary outcome was the weekly
      rate of active commuting to school. Daily moderate-to-vigorous physical activity,
      measured by accelerometers, was a secondary outcome. Child self-efficacy
      (alpha=0.75), parent self-efficacy (alpha=0.88), and parent outcome expectations
      (alpha=0.78) were independent variables. Participant characteristics (age,
      gender, race/ethnicity, distance from home to school, acculturation, and BMI
      percentile) were independent sociodemographic variables. We used mixed-model
      regression analyses to account for clustering by school and a stepwise procedure
      with backward elimination of non-significant interactions and covariates to
      identify significant moderators and predictors. School-level observations of
      student pedestrians were assessed and compared using chi-square tests of
      independence. RESULTS: Among our sample, which was 61.7% Latino, the overall rate
      of active commuting to school was 43%. In the mixed model for active commuting to
      school, parent self-efficacy (std. beta = 0.18, p=0.018) and age (std. beta =
      0.18, p=0.018) were positively related. Latino students had lower rates of active
      commuting to school than non-Latinos ( 16.5%, p=0.040). Distance from home to
      school was inversely related to active commuting to school (std. beta = 0.29,
      p<0.001). In the mixed model for moderate-to-vigorous physical activity, active
      commuting to school was positively associated (std. beta = 0.31, p <0.001). Among
      the Latino subsample, child acculturation was negatively associated with active
      commuting to school (std. beta = -0.23, p=0.01). With regard to school-level
      pedestrian safety observations, 37% of students stopped at the curb and 2.6%
      looked left-right-left before crossing the street. CONCLUSION: Although still
      below national goals, the rate of active commuting was relatively high, while the
      rate of some pedestrian safety behaviors was low among this low-income, ethnic
      minority population. Programs and policies to encourage safe active commuting to
      school are warranted and should consider the influence of parents, acculturation,
      and ethnicity.

PMID- 21874161
TI  - A Hypotensive Episode Predictor for Intensive Care based on Heart Rate and Blood
      Pressure Time Series.
AB  - In the intensive care unit (ICU), prompt therapeutic intervention to hypotensive
      episodes (HEs) is a critical task. Advance alerts that can prospectively identify
      patients at risk of developing an HE in the next few hours would be of
      considerable clinical value. In this study, we developed an automated, artificial
      neural network HE predictor based on heart rate and blood pressure time series
      from the MIMIC II database. The gap between prediction time and the onset of the
      30-minute target window was varied from 1 to 4 hours. A 30-minute observation
      window preceding the prediction time provided input information to the predictor.
      While individual gap sizes were evaluated independently, weighted posterior
      probabilities based on different gap sizes were also investigated. The results
      showed that prediction performance degraded as gap size increased and the
      weighting scheme induced negligible performance improvement. Despite low positive
      predictive values, the best mean area under ROC curve was 0.934.

PMID- 21874162
TI  - Curing Cholera: Pathogens, Places and Poverty in South Asia.

PMID- 21874164
TI  - Force Control of Flexible Catheter Robots for Beating Heart Surgery.
AB  - Recent developments in cardiac catheter technology promise to allow physicians to
      perform most cardiac interventions without stopping the heart or opening the
      chest. However, current cardiac devices, including newly developed catheter
      robots, are unable to accurately track and interact with the fast moving cardiac
      tissue without applying potentially damaging forces. This paper examines the
      challenges of implementing force control on a flexible robotic catheter. In
      particular, catheter friction and backlash must be compensated when controlling
      tissue interaction forces. Force controller designs are introduced and evaluated
      experimentally in a number of configurations. The controllers are based on the
      inner position loop force control approach where the position trajectory is
      adjusted to achieve a desired force on the target. Friction and backlash
      compensation improved force tracking up to 86% with residual RMS errors of 0.11 N
      while following a prerecorded cardiac tissue trajectory with accelerations of up
      to 3800 mm/s(2). This performance provides sufficient accuracy to enable a wide
      range of beating heart surgical procedures.

PMID- 21874163
TI  - Response and resistance to NF-kappaB inhibitors in mouse models of lung
      adenocarcinoma.
AB  - Lung adenocarcinoma is a leading cause of cancer death worldwide. We recently
      showed that genetic inhibition of the NF-kappaB pathway affects both the
      initiation and the maintenance of lung cancer, identifying this pathway as a
      promising therapeutic target. In this investigation, we tested the efficacy of
      small-molecule NF-kappaB inhibitors in mouse models of lung cancer. In murine
      lung adenocarcinoma cell lines with high NF-kappaB activity, the proteasome
      inhibitor bortezomib efficiently reduced nuclear p65, repressed NF-kappaB target
      genes, and rapidly induced apoptosis. Bortezomib also induced lung tumor
      regression and prolonged survival in tumor-bearing Kras(LSL
      G12D/wt);p53(flox/flox) mice but not in Kras(LSL-G12D/wt) mice. After repeated
      treatment, initially sensitive lung tumors became resistant to bortezomib. A
      second NF-kappaB inhibitor, Bay-117082, showed similar therapeutic efficacy and
      acquired resistance in mice. Our results using preclinical mouse models support
      the NF-kappaB pathway as a potential therapeutic target for a defined subset of
      lung adenocarcinoma. SIGNIFICANCE: Using small-molecule compounds that inhibit NF
      kappaB activity, we provide evidence that NF-kappaB inhibition has therapeutic
      efficacy in the treatment of lung cancer. Our results also illustrate the value
      of mouse models in validating new drug targets in vivo and indicate that acquired
      chemoresistance may later influence bortezomib treatment in lung cancer.

PMID- 21874165
TI  - Determination of resin acids during production of wood pellets--a comparison of
      HPLC/ESI-MS with the GC/FID MDHS 83/2 method.
AB  - Resin acids are constituents of natural and technical products of widespread use.
      Exposure is known to cause health effects in the airways and on the skin. Liquid
      chromatography/positive ion electrospray-mass spectrometry (HPLC/pos ESI-MS) was
      investigated for determination of 7-oxodehydroabietic (7-OXO), dehydroabietic
      (DHAA) and abietic acid (AA) in wood dust-containing air samples as a
      derivatisation-free alternative to the GC/FID HSE method 83/2, developed by the
      Health and Safety Executive UK. The resin acid 7-OXO was measured as a marker for
      oxidised resin acids, which are known to be the main contact allergens in
      colophonium. The found detection limits were 0.42 ng m(-3) for 7-OXO, 5.2 ng m(
      3) for DHAA and 9.4 ng m(-3) for AA, respectively, which are considerably lower
      than with the GC/FID method (24, 115 and 89 ng m(-3)). The two methods correlated
      well, although consistently and significantly lower concentrations of 7-OXO were
      detected with LC/MS. The higher concentration of this compound with MDHS 83/2 is
      suggested to be an artefact from the derivatisation step in the presence of
      soluble wood dust remains.

PMID- 21874166
TI  - Characterization of dandelion species using 1H NMR- and GC-MS-based metabolite
      profiling.
AB  - Taraxacum, known as dandelion, is a large genus of plants in the family
      Asteraceae. Pharmacological studies have shown that these plants display a wide
      variety of medicinal properties because Taraxacum extracts contain many
      pharmacologically active metabolites that display anti-inflammatory,
      antinociceptive, antioxidant, and anticancer activity. Each plant species
      displays several different natural constituents, the majority of which have not
      been studied as no global metabolite screen of the diverse Taraxacum species has
      been performed. In this study, we investigated the metabolite difference in three
      species of Taraxacum (T. coreanum, T. officinale, and T. platycarpum) by (1)H NMR
      spectroscopy and gas chromatography-mass spectrometry (GC-MS) coupled with
      multivariate statistical analyses. The aim of this study was to identify the
      different chemical compositions of the polar and nonpolar extracts in these
      species. A partial least-squares discriminant analysis showed a significantly
      higher separation among nonpolar extracts (mainly fatty acids and sterols)
      compared to polar extracts (mainly amino acids, organic acids, and sugars)
      between these species. A one-way ANOVA was performed to statistically certify the
      metabolite differences of these nonpolar extracts. Taken together, these data
      suggest that a metabolomic approach using combined (1)H NMR and GC-MS analysis is
      an effective analytical method to differentiate biochemical compositions among
      different species in plants.

PMID- 21874167
TI  - Insulin-binding aptamer-conjugated graphene oxide for insulin detection.
AB  - This paper describes a simple and sensitive aptamer/graphene oxide (GO) based
      assay for insulin detection. GO can protect DNA from nuclease cleavage, but
      aptamers can be detached from the GO surface by specific target binding. This
      exposes the aptamers to enzymatic cleavage and releases the target for a new
      cycle. Cycling of targets leads to significant signal amplification and low LOD.

PMID- 21874168
TI  - Optical trapping for the characterization of amyloid-beta aggregation kinetics.
AB  - Alzheimer's disease (AD) is marked by the accumulation of neuronal plaques from
      insoluble amyloid-beta (Abeta) peptides. Growing evidence for the role of Abeta
      oligomers in neuronal cell cytotoxicity and pathogenesis has prompted the
      development of novel techniques to better understand the early stages of
      aggregation. Near infrared (NIR) optical trapping was applied to characterize the
      early stages of Abeta aggregation in the presence of a beta-sheet intercalating
      dye, Congo Red (CR), as the fluorescent marker. The integration of fluorescence
      analysis with NIR optical trapping has provided a new outlook into the first two
      hours of Abeta aggregation.

PMID- 21874173
TI  - A trinuclear bright red luminophore containing cyclometallated Ir(III) motifs.
AB  - The trinuclear complex [{Ir(ppy)(2)}(3)(L(1))(2)](OTf)(3) (1) is a bright red
      luminophore whereas the monomer [Ir(ppy)(2)L(2)](OTf) (2) exhibits emission in
      the green region.

PMID- 21874174
TI  - Patterning small-molecule biocapture surfaces: microcontact insertion printing
      vs. photolithography.
AB  - Chemical patterns prepared by self-assembly, combined with soft lithography or
      photolithography, are directly compared. Pattern fidelity can be controlled in
      both cases but patterning at the low densities necessary for small-molecule probe
      capture of large biomolecule targets is better accomplished using microcontact
      insertion printing (MUCIP). Surfaces patterned by MUCIP are used to capture
      biomolecule binding partners for the small molecules dopamine and biotin.

PMID- 21874175
TI  - Simple methods for tuning the pore diameter of mesoporous carbon.
AB  - The organic-organic self-assembly method with Resorcinol (R)/Formaldehyde (F) and
      Pluronic F127 has been employed to synthesize mesoporous carbon (MC). The pore
      diameter of the MC has been tuned from 7 to 12.5 nm by changing the molar ratio
      of carbon sources to surfactant and polymerization time.

PMID- 21874176
TI  - beta-Cyclodextrin for design of alumina supported cobalt catalysts efficient in
      Fischer-Tropsch synthesis.
AB  - Addition of beta-cyclodextrin during catalyst preparation strongly affects the
      structure and catalytic performance of alumina supported cobalt catalysts for
      Fischer-Tropsch synthesis. Impregnation of the support with solutions containing
      beta-cyclodextrin leads to higher metal dispersion and spectacularly enhances
      both reaction rate and heavy hydrocarbons productivity in Fischer-Tropsch
      synthesis.

PMID- 21874177
TI  - Fabrication of a dispersible graphene/gold nanoclusters hybrid and its potential
      application in electrogenerated chemiluminescence.
AB  - A dispersible graphene/gold nanoclusters hybrid in aqueous solution was
      fabricated in situ based on the bilayer graphene template, and its
      electrogenerated chemiluminescence (ECL) behavior was studied.

PMID- 21874178
TI  - Fluorescence sensing of caffeine in water with polysulfonated pyrenes.
AB  - The commercially available fluorescence dye 8-hydroxypyrene-1,3,6-trisulfonate
      (HPTS) can be used as a selective molecular probe for the detection of caffeine
      in aqueous solution.

PMID- 21874179
TI  - A novel pathway for maytansinoid release from thioether linked antibody-drug
      conjugates (ADCs) under oxidative conditions.
AB  - A novel pathway for ex vivo maytansinoid release from thioether linked antibody
      maytansinoid conjugates (AMCs) upon incubation in human plasma has been
      identified. A thioether succinimide-linked AMC can undergo chemical oxidation
      followed by sulfoxide elimination under mild aqueous conditions (pH 5.5-7.5, 37 
      degrees C). Oxidized thioether-linked AMCs exhibit high, target-specific
      cytotoxicity toward cancer cells.

PMID- 21874180
TI  - A facile two-step dipping process based on two silica systems for a
      superhydrophobic surface.
AB  - A silica microsphere suspension and a silica sol are employed in a two-step
      dipping process for the preparation of a superhydrophobic surface. It's not only
      a facile way to achieve the lotus effect, but can also create a multi-functional
      surface with different wetabilities, adhesive forces and transparencies.

PMID- 21874181
TI  - Formation of polypseudorotaxane networks by cross-linking the quadruple hydrogen
      bonded linear supramolecular polymers via bisparaquat molecules.
AB  - The creation of novel crown ether-paraquat polypseudorotaxane networks,
      constructed by bisparaquat monomers threading into the cavity of the crown ether
      units of linear supramolecular polymers that are formed based on the quadruple
      hydrogen bonded unit ureidopyrimidinone (Upy) in the concentrated solution, is
      described.

PMID- 21874182
TI  - Highlights from the 46th EUCHEM Conference on stereochemistry, Burgenstock,
      Switzerland, May 2011.

PMID- 21874183
TI  - Deceleration of supersonic beams using inhomogeneous electric and magnetic
      fields.
AB  - Methods for the production of cold atomic and molecular samples relying on the
      deceleration of pulsed supersonic beams are described and a review of the
      corresponding literature is presented. These methods include multistage Stark
      deceleration, multistage Zeeman deceleration, and Rydberg-Stark deceleration.
      Recent applications of the cold samples produced with these techniques are
      summarized.

PMID- 21874184
TI  - Radiative efficiencies for fluorinated esters: indirect global warming potentials
      of hydrofluoroethers.
AB  - Density Functional Theory (DFT) has been used with an empirically-derived
      correction for the wavenumbers of vibrational band positions to predict the
      infrared spectra of several fluorinated esters (FESs). Radiative efficiencies
      (REs) were then determined using the method of Pinnock et al. and these were used
      with atmospheric lifetimes from the literature to determine the direct global
      warming potentials of FESs. FESs, in particular fluoroalkylacetates,
      alkylfluoroacetates and fluoroalkylformates, are potential greenhouse gases and
      their likely long atmospheric lifetimes and relatively large REs, compared to
      their parent HFEs, make them active contributors to global warming. Here, we use
      the concept of indirect global warming potential (indirect GWP) to assess the
      contribution to the warming of several commonly used HFEs emitted from the
      Earth's surface, explicitly taking into account that these HFEs will be converted
      into the corresponding FESs in the troposphere. The indirect GWP can be
      calculated using the radiative efficiencies and lifetimes of the HFE and its
      degradation FES products. We found that the GWPs of those studied HFEs which have
      the smallest direct GWP can be increased by 100-1600% when taking account of the
      cumulative effect due to the secondary FESs formed during HFE atmospheric
      oxidation. This effect may be particularly important for non-segregated HFEs and
      some segregated HFEs, which may contribute significantly more to global warming
      than can be concluded from examination of their direct GWPs.

PMID- 21874185
TI  - Zn(II) Robson macrocycles as templates for chelating diphosphines.
AB  - Chelating diphosphines were constructed using dinuclear Zn(II) complexes of
      Robson macrocycles (Zn-RMCs) as templates. The assembly process is driven by the
      interaction between the metal centers (Lewis acids) with anionic and neutral
      Lewis base-functionalized monophosphines. The stability of the final structure
      depends on the geometry and the affinity of the functional groups of the ditopic
      phosphines and on the structure of the RMC. In the free ligand the ditopic
      phosphines coordinate at opposite faces of the pseudo-planar macrocycle as is
      shown in the molecular structure of several of the assemblies, according to X-ray
      diffraction. Pre-organization of the system by coordinating the phosphorus atoms
      to a transition metal center enforced coordination of the functional groups at
      the same face of the RMC. For several templated diphosphines cis-PtCl(2)
      complexes were identified by NMR. The in situ assembled diphosphines showed a
      chelating effect in the rhodium catalyzed hydroformylation of 1-octene.
      Combination of Zn-RMC 3 and phosphine A gave the highest l/b ratio (13) in
      acetonitrile.

PMID- 21874186
TI  - Construction of 1-D 4f and 3d-4f coordination polymers with flexible Schiff base
      ligands.
AB  - Three new lanthanide 1-D coordination polymers
      ({[Ln(2)(H(2)L)(OAc)(6)].EtOH.2H(2)O}(n) (Ln = Eu (1), Er (2)) and
      {YbNiLCl(OAc)(2)(H(2)O)}(n) (3)) and a heterobinuclear complex
      [YbNiLCl(3)(H(2)O)(3)] (4) are reported which are formed from salen type Schiff
      base ligands H(2)L (H(2)L = N,N'-bis(3-methoxysalicylidene)butane-1,4-diamine).
      The polymeric structures are formed by bridging H(2)L units in the case of 1 and
      2, and by acetate groups in 3. The structures of 1-4 were determined by single
      crystal X-ray crystallographic studies and their luminescence properties in MeCN
      solution were determined.

PMID- 21874187
TI  - Major impact of N-methylation on cytotoxicity and hydrolysis of salan Ti(IV)
      complexes: sterics and electronics are intertwined.
AB  - A series of Ti(IV) complexes containing diamino bis(phenolato) "salan" type
      ligands with NH coordination were prepared, and their hydrolysis and cytotoxicity
      were analyzed and compared to the N-methylated analogues. Substituting methyl
      groups on the coordinative nitrogen donor of highly active and stable Ti(IV)
      salan complexes with H atoms has two main consequences: the hydrolysis rate
      increases and the cytotoxic activity diminishes. In addition, the small
      modification of a single replacement of Me with H leads to a different major
      hydrolysis product, where a dinuclear Ti(IV) complex with two bridging oxo
      ligands is obtained, as characterized by X-ray crystallography, rather than a
      trinuclear cluster. A partial hydrolysis product containing a single oxo bridge
      was also crystallographically analyzed. Investigation of a series of complexes
      with NH donors of different steric and electronic effects revealed that
      cytotoxicity may be restored by fine tuning these parameters even for complexes
      of low stability.

PMID- 21874188
TI  - Influence of antioxidant rich fresh vegetable juices on starch induced
      postprandial hyperglycemia in rats.
AB  - This research analyzed the major chemical components and multiple antioxidant
      activities present in the fresh juice of eight vegetables, and studied their
      influence on starch induced postprandial glycemia in rats. A SDS-PAGE based
      protein fingerprint of each vegetable juice was also prepared. The yields of
      juice, chemical components like total proteins, total polyphenols, total
      flavonoids, total anthocyanins and free radicals like the ABTS(+) cation, DPPH,
      H(2)O(2), scavenging activities and reducing properties for NBT and FeCl(3)
      showed wide variations. Vegetable juice from brinjal ranked first in displaying
      total antioxidant capacity. Pretreatment of rats with vegetable juices moderated
      starch induced postprandial glycemia. The fresh juice from the vegetables ridge
      gourd, bottle gourd, ash gourd and chayote significantly mitigated postprandial
      hyperglycemic excursion. Total polyphenol concentrations present in vegetable
      juices positively influenced ABTS(+) scavenging activity and total antioxidant
      capacity. However, NBT reducing activity of juices was positively affected by
      total protein concentration. Contrarily, however, high polyphenol content in
      vegetable juice was observed to adversely affect the postprandial
      antihyperglycemic activity of vegetable juices. This is the first report
      exploring antihyperglycemic activity in these vegetable juices and highlights the
      possible adverse influence of high polyphenol content on the antihyperglycemic
      activity of the vegetable juices.

PMID- 21874189
TI  - Towards a quantitative model of the post-synaptic proteome.
AB  - The postsynaptic compartment of the excitatory glutamatergic synapse contains
      hundreds of distinct polypeptides with a wide range of functions (signalling,
      trafficking, cell-adhesion, etc.). Structural dynamics in the post-synaptic
      density (PSD) are believed to underpin cognitive processes. Although functionally
      and morphologically diverse, PSD proteins are generally enriched with specific
      domains, which precisely define the mode of clustering essential for signal
      processing. We applied a stochastic calculus of domain binding provided by a rule
      based modelling approach to formalise the highly combinatorial signalling pathway
      in the PSD and perform the numerical analysis of the relative distribution of
      protein complexes and their sizes. We specified the combinatorics of protein
      interactions in the PSD by rules, taking into account protein domain structure,
      specific domain affinity and relative protein availability. With this model we
      interrogated the critical conditions for the protein aggregation into large
      complexes and distribution of both size and composition. The presented approach
      extends existing qualitative protein-protein interaction maps by considering the
      quantitative information for stoichiometry and binding properties for the
      elements of the network. This results in a more realistic view of the
      postsynaptic proteome at the molecular level.

PMID- 21874190
TI  - A comprehensive overview of computational protein disorder prediction methods.
AB  - Over the past decade there has been a growing acknowledgement that a large
      proportion of proteins within most proteomes contain disordered regions.
      Disordered regions are segments of the protein chain which do not adopt a stable
      structure. Recognition of disordered regions in a protein is of great importance
      for protein structure prediction, protein structure determination and function
      annotation as these regions have a close relationship with protein expression and
      functionality. As a result, a great many protein disorder prediction methods have
      been developed so far. Here, we present an overview of current protein disorder
      prediction methods including an analysis of their advantages and shortcomings. In
      order to help users to select alternative tools under different circumstances, we
      also evaluate 23 disorder predictors on the benchmark data of the most recent
      round of the Critical Assessment of protein Structure Prediction (CASP) and
      assess their accuracy using several complementary measures.

PMID- 21874191
TI  - Proliferating dynamic modeling in systems biology studies.

PMID- 21874192
TI  - Teflon AF-2400 mediated gas-liquid contact in continuous flow
      methoxycarbonylations and in-line FTIR measurement of CO concentration.
AB  - We report on the development of a continuous flow process for the palladium
      catalysed methoxycarbonylation of aryl, heteroaromatic and vinyl iodides and an
      aryl bromide using a Teflon AF-2400 based Tube-in-Tube reactor to mediate the
      selective permeation of carbon monoxide into solution at elevated pressures. The
      low volume of pressurised gas within the reactor (5.6 mL) offers the potential
      for an enhanced safety profile compared to batch processes. We also present
      preliminary results for the use of in situ FTIR to measure solution
      concentrations of carbon monoxide and demonstrate the use of a second reactor to
      effect the removal of carbon monoxide from the flow stream.

PMID- 21874193
TI  - CdSe/ZnS core shell quantum dot-based FRET binary oligonucleotide probes for
      detection of nucleic acids.
AB  - We report the design, synthesis, and characterization of a binary
      oligonucleotideprobe for selective DNA or RNA detection. The probe is based on
      fluorescence resonance energy transfer (FRET) from quantum dot (CdSe/ZnS core
      shell) DNA conjugates to organic dye (cyanine-5) DNA conjugates. Selective
      hybridization of the donor/acceptor DNA conjugates to target DNA enhances FRET
      and a change in fluorescence signature was observed.

PMID- 21874194
TI  - Meta-tetra(hydroxyphenyl)chlorin-loaded liposomes sterically stabilised with
      poly(ethylene glycol) of different length and density: characterisation, in vitro
      cellular uptake and phototoxicity.
AB  - We studied the effects of density and thickness of PEG coating on in vitro
      cellular uptake, and dark- and photo-toxicity of liposomal formulations (Fospeg)
      of the photodynamic agent meta-tetrahydroxyphenyl chlorin (m-THPC). The cellular
      uptake of various Fospeg formulations was determined by flow cytometry in CCD
      34Lu human normal fibroblasts and A549 lung cancer cells. Dark and light-induced
      cytotoxicity was measured by MTS assay after exposure to increasing
      concentrations of Fospeg only and followed by irradiation with red light.
      Intracellular localization of m-THPC delivered by Fospeg was determined by
      fluorescence microscopy. The studies were carried out in comparison with m-THPC
      delivered by the standard solvent. In the dark all Fospeg formulations were less
      cytotoxic than m-THPC in standard solvent (ethanol/poly(ethylene glycol
      400/water; 20 : 30 : 50 by vol.) and cytotoxicity decreased by increasing
      PEGylation. m-THPC delivered as Fospeg was internalised by endocytosis and
      localised mainly in the Golgi apparatus and endoplasmic reticulum. The efficiency
      of cellular uptake of Fospeg was reduced by 30-40% with respect to m-THPC in
      standard solution causing a slight reduction of the phototoxicity but without
      serious impairment of the efficacy of the treatment. Our study suggests that
      PEGylated liposomes are promising nanocarriers for the delivery of
      photosensitisers for photodynamic therapy because they reduce dark cytotoxicity
      while preserving therapeutic efficacy.

PMID- 21874195
TI  - Inactivation of Enterococcus faecalis by TiO2-mediated UV and solar irradiation
      in water and wastewater: culture techniques never say the whole truth.
AB  - In this work, the disinfection efficiency of water and secondary treated
      wastewater by means of UV-A, UV-C and solar irradiation in the presence or
      absence of TiO(2), using a reference strain of Enterococcus faecalis as faecal
      indicator, was evaluated. Operating parameters such as TiO(2) loading (0-1500 mg
      L(-1)), initial bacterial concentration (2 * 10(2)-10(8) CFU mL(-1)) and
      treatment time (up to 120 min) were assessed concerning their impact on
      disinfection. E. faecalis inactivation was monitored by the conventional culture
      method and real-time PCR. Regarding photocatalytic treatment, disinfection
      efficiency was improved by increasing TiO(2) concentration and bacterial
      inactivation took place in relatively short treatment times. Comparing the three
      disinfection methods, it was observed that UV-C irradiation yielded a better
      efficiency during water treatment than UV-A and solar irradiation. Furthermore,
      UV-A was more efficient than solar irradiation in the presence of the same
      loading of TiO(2). Regarding real wastewater, it was observed that only UV-C
      irradiation was capable of totally inactivating E. faecalis population in a short
      time. Screening the results obtained from both applied techniques (culture method
      and real-time PCR), there was a discrepancy, regarding the recorded time periods
      of total bacterial inactivation. Real-time PCR data revealed that longer periods
      are needed for 100% bacterial reduction during the treatments tested compared to
      the estimated time by culture method. This is probably attributed to the
      phenomenon of "viable but not culturable bacteria", caused by stressed conditions
      induced during disinfection experiments. Taking into account the contrast of
      results and in order to perform a thorough evaluation of disinfection techniques,
      conventional culture method should be accompanied by a DNA-based method.
      According to our findings, real-time PCR proved to be a reliable and accurate
      molecular tool for the identification and quantification of bacterial indicators,
      like E. faecalis, in aquatic samples after disinfection treatment.

PMID- 21874196
TI  - Microfluidic formation of pH responsive 5CB droplets decorated with PAA-b-LCP.
AB  - We are reporting for the first time the pH responsiveness of liquid crystal (LC)
      microdroplets decorated with an amphiphilic block copolymer of PAA-b-LCP. We
      successfully demonstrated the adsorption of block copolymer on LC droplets by
      fluorescence microscopy and pH response to the radial-to-bipolar orientational
      change of the LC droplets by changing pH from 12 to 2 through the polarized
      optical microscope (POM). We believe that our results may pave the way for the
      generation of monodisperse droplets decorated by various amphiphilic block
      copolymers which respond to several kinds of the external stimuli. These
      developments may be important for potential applications of the LC droplets in
      sensing and encapsulation fields.

PMID- 21874197
TI  - Wavelet unfolded partial least squares for near-infrared spectral quantitative
      analysis of blood and tobacco powder samples.
AB  - Continuous wavelet transform (CWT) has been shown to be a high-performance signal
      processing technique in multivariate calibration. However, the signal processed
      by CWT with a specific wavelet may account for only a part of the information. To
      effectively utilize more abundant information contained in analytical signals, a
      method, named as wavelet unfolded partial least squares (WUPLS), was proposed. In
      the approach, the measured dataset is firstly extended by CWT with different
      wavelets, and then partial least squares (PLS) is employed to develop the
      quantitative model between the extended dataset and the target values. In order
      to select the representative wavelets, principal component analysis (PCA) is used
      to investigate the distribution of the signals obtained by CWT with different
      wavelets. The performance of the method was tested with blood and tobacco powder
      samples. Compared with the results obtained by PLS methods, the WUPLS method
      combined with signal processing techniques is proven to be a promising tool for
      improving the near-infrared (NIR) spectral analysis of complex samples.

PMID- 21874198
TI  - A novel non-enzymatic glucose sensor modified with Fe2O3 nanowire arrays.
AB  - Fe(2)O(3) was generally considered to be biologically and electrochemically
      inert, and its electrocatalytic functionality has been rarely realized directly
      in the past. In this work, Fe(2)O(3) nanowire arrays were synthesized and
      electrochemically characterized. The as prepared Fe(2)O(3) nanomaterial was
      proved to be an ideal electrode material due to the intrinsic peroxidase-like
      catalytic activity. The Fe(2)O(3) nanowire array modified glucose sensor
      exhibited excellent biocatalytic performance towards the oxidation of glucose
      with a response time of <6 s, a linear range between 0.015-8 mM, and sensitivity
      of 726.9 MUA mM(-1)cm(-1). Additionally, a high sensing selectivity towards
      glucose oxidation in the presence of ascorbic acid (AA) and dopamine (DA) has
      also been obtained at their maximum physiological concentrations, which makes the
      Fe(2)O(3) nanomaterial promising for the development of effective electrochemical
      sensors for practical applications.

PMID- 21874199
TI  - Standardization of Raman spectra for transfer of spectral libraries across
      different instruments.
AB  - In this paper we evaluate methods for standardization of Raman spectra that are
      required to improve spectral correlation computations between spectra measured on
      different instruments. Five commercially-available 785 nm Raman spectrometers
      from different vendors were included in the study. These spectrometers have
      diverse specifications and performance levels and range in size from laboratory
      based instruments to field-deployable portable and handheld platforms. Since each
      Raman spectrometer has different characteristics, spectra obtained on one
      instrument cannot readily be compared to a library acquired on a different
      instrument without performing various types of spectral corrections
      (standardization). We outline a procedure that combines previously established
      Raman shift and intensity correction protocols with a resolution matching step to
      facilitate the comparison of a centralized master library with spectra acquired
      on different geographically distributed Raman spectrometers. The standardization
      procedure is effective in reducing the inherent instrument-to-instrument
      variability so that spectra from different spectrometers can be compared and
      reliable results obtained using library-based spectral correlation methods. The
      findings have important implications for the ability to transfer Raman spectral
      libraries between instruments.

PMID- 21874200
TI  - A biological breadboard platform for cell adhesion and detachment studies.
AB  - The dynamic nature of cell adhesion and detachment, which plays a critical role
      in a variety of physiological and pathological phenomena, still remains unclear.
      This motivates the pursuit of controllable manipulation of cell adhesion and
      detachment for a better understanding of cellular dynamics. Here we present an
      addressable, multifunctional, and reusable platform, termed the biological
      breadboard (BBB), for spatiotemporal manipulation of cell adhesion and detachment
      at cellular and subcellular levels. The BBB, composed of multiple gold electrodes
      patterned on a Pyrex substrate, is surface-modified with arginine-glycine
      aspartic acid terminated thiol (RTT) and polyethylene glycol (PEG) to achieve a
      cell-adhesive surface on the gold electrodes and a cell-resistive surface on the
      Pyrex substrate, respectively. Cell adhesion is regulated by the steric repulsion
      of PEG chains, while cell detachment is controlled by the reductive desorption of
      a gold-thiol self-assembled monolayer (SAM) at an activation potential of -0.90
      to -1.65 V. Experimental characterizations using NIH 3T3 fibroblasts are
      presented to demonstrate the utility of our device.

PMID- 21874201
TI  - Resolving natural product epimer spectra by matrix-assisted DOSY.
AB  - High resolution diffusion-ordered NMR spectroscopy allows the separation of
      signals from different species based on their diffusion coefficients. In general
      this requires that the NMR spectra of the components do not have overlapping
      signals, and that the diffusion coefficients are significantly different.
      Modifying the solvent matrix in which a sample is dissolved can change the
      diffusion coefficients observed, allowing resolution ("matrix-assisted DOSY"). We
      show here that dissolving the two naturally-occurring epimers of naringin in an
      aqueous solution of beta-cyclodextrin causes both shift and diffusion changes,
      allowing the signals of the epimers to be distinguished. Chiral matrix-assisted
      DOSY has the potential to allow simple resolution and assignment of the spectra
      of epimers and enantiomers, without the need for derivatisation or for titration
      with a shift reagent.

PMID- 21874202
TI  - A new solvent polymeric membrane electrode incorporating poly(N
      isopropylacrylamide) as a polymer.
AB  - Here, we report on a new solvent polymeric membrane electrode incorporating
      thermoresponsive poly(N-isopropylacrylamide) (PIPA) as a polymer with the lower
      critical solution temperature (LCST) of ca. 32  degrees C. The response of the
      solvent polymeric membrane electrode to the ions changes at 25 and 40  degrees C.
      Pulsed NMR analyses demonstrated the novel effects of the LCST behaviour on the
      potentiometric polymeric membrane.

PMID- 21874203
TI  - Localized surface plasmon resonance interfaces coated with poly[3
      (pyrrolyl)carboxylic acid] for histidine-tagged peptide sensing.
AB  - The paper reports on a novel localized surface plasmon resonance (LSPR) substrate
      architecture for the immobilization and detection of histidine-tagged peptides.
      The LSPR interface consists of an ITO (indium tin oxide) substrate coated with
      gold nanostructures. The latter are obtained by thermal deposition of a thin (2
      nm thick) gold film followed by post-annealing at 500  degrees C. The LSPR
      interface was coated with poly[3-(pyrrolyl)carboxylic acid] thin films using
      electrochemical means. The ability of the LSPR interfaces coated with poly[3
      (pyrrolyl)carboxylic acid] to chelate copper ions was investigated. Once loaded
      with metal ions, the modified LSPR interface was able to bind specifically to
      histidine-tagged peptides. The binding process was followed using LSPR.

PMID- 21874204
TI  - Synthesis of substituted [3]dendralenes and their unique cycloaddition reactions.
AB  - Dimethylsulfonium methylide mediated olefination of 2-phenylethenylidene
      phosphonoacetate followed by the Horner-Wadsworth-Emmons reaction with aromatic
      aldehydes provided access to reactive 1,5-diaryl-2-ethoxycarbonyl [3]dendralenes
      which in situ underwent Diels-Alder cyclodimerisation leading to highly
      functionalised cyclohexenes with very high regio- and stereoselectivity.

PMID- 21874206
TI  - Towards a robust description of intrinsic protein disorder using nuclear magnetic
      resonance spectroscopy.
AB  - In order to understand the conformational behaviour of Intrinsically Disordered
      Proteins (IDPs), it is essential to develop a molecular representation of the
      partially folded state. Due to the very large number of degrees of conformational
      freedom available to such a disordered system, this problem is highly
      underdetermined. Characterisation therefore requires extensive experimental data,
      and novel analytical tools are required to exploit the specific conformational
      sensitivity of different experimental parameters. In this review we concentrate
      on the use of nuclear magnetic resonance (NMR) spectroscopy for the study of
      conformational behaviour of IDPs at atomic resolution. Each experimental NMR
      parameter is sensitive to different aspects of the structural and dynamic
      behaviour of the disordered state and requires specific consideration of the
      relevant averaging properties of the physical interaction. In this review we
      present recent advances in the description of disordered proteins and the
      selection of representative ensembles on the basis of experimental data using
      statistical coil sampling from flexible-meccano and ensemble selection using
      ASTEROIDS. Using these tools we aim to develop a unified molecular representation
      of the disordered state, combining complementary data sets to extract a
      meaningful description of the conformational behaviour of the protein.

PMID- 21874205
TI  - Roles of intrinsic disorder in protein-nucleic acid interactions.
AB  - Interactions between proteins and nucleic acids typify the role of disordered
      segments, linkers, tails and other entities in the function of complexes that
      must form with high affinity and specificity but which must be capable of
      dissociating when no longer needed. While much of the emphasis in the literature
      has been on the interactions of disordered proteins with other proteins, disorder
      is also frequently observed in nucleic acids (particularly RNA) and in the
      proteins that interact with them. The interactions of disordered proteins with
      DNA most often manifest as molding of the protein onto the B-form DNA structure,
      although some well-known instances involve remodeling of the DNA structure that
      seems to require that the interacting proteins be disordered to various extents
      in the free state. By contrast, induced fit in RNA-protein interactions has been
      recognized for many years-the existence and prevalence of this phenomenon
      provides the clearest possible evidence that RNA and its interactions with
      proteins must be considered as highly dynamic, and the dynamic nature of RNA and
      its multiplicity of folded and unfolded states is an integral part of its nature
      and function.

PMID- 21874207
TI  - Straightforward synthesis of 1-alkyl-2-(trifluoromethyl)aziridines starting from
      1,1,1-trifluoroacetone.
AB  - An efficient and straightforward approach towards the synthesis of 1-alkyl-2
      (trifluoromethyl)aziridines starting from 1,1,1-trifluoroacetone via imination,
      alpha-chlorination, hydride reduction and ring closure was developed. In
      addition, novel primary beta-iodo amines were obtained by regioselective ring
      opening of these 2-(trifluoromethyl)aziridines using alkyl iodides, and their
      synthetic potential was demonstrated by converting them into novel alpha-CF(3)
      beta-phenylethylamines upon treatment with lithium diphenylcuprate.

PMID- 21874208
TI  - Evaluation of the measurement properties of self-reported health-related work
      functioning instruments among workers with common mental disorders.
AB  - OBJECTIVES: During the past decade, common mental disorders (CMD) have emerged as
      a major public and occupational health problem in many countries. Several
      instruments have been developed to measure the influence of health on functioning
      at work. To select appropriate instruments for use in occupational health
      practice and research, the measurement properties (eg, reliability, validity,
      responsiveness) must be evaluated. The objective of this study is to appraise
      critically and compare the measurement properties of self-reported health-related
      work-functioning instruments among workers with CMD. METHODS: A systematic review
      was performed searching three electronic databases. Papers were included that:
      (i) mainly focused on the development and/or evaluation of the measurement
      properties of a self-reported health-related work-functioning instrument; (ii)
      were conducted in a CMD population; and (iii) were fulltext original papers.
      Quality appraisal was performed using the consensus-based standards for the
      selection of health status measurement instruments (COSMIN) checklist. RESULTS:
      Five papers evaluating measurement properties of five self-reported health
      related work-functioning instruments in CMD populations were included. There is
      little evidence available for the measurement properties of the identified
      instruments in this population, mainly due to low methodological quality of the
      included studies. CONCLUSIONS: The available evidence on measurement properties
      is based on studies of poor-to-fair methodological quality. Information on a
      number of measurement properties, such as measurement error, content validity,
      and cross-cultural validity is still lacking. Therefore, no evidence-based
      decisions and recommendations can be made for the use of health-related work
      functioning instruments. Studies of high methodological quality are needed to
      properly assess the existing instruments' measurement properties.

PMID- 21874209
TI  - Mental distress among shift workers in Norwegian offshore petroleum industry-
      relative influence of individual and psychosocial work factors.
AB  - OBJECTIVE: This study aimed to investigate the association between individual and
      psychosocial work factors and mental distress among offshore shift workers in the
      Norwegian petroleum industry. METHODS: All 2406 employees of a large Norwegian
      oil and gas company, who worked offshore during a two-week period in August 2006,
      were invited to participate in the web-based survey. Completed questionnaires
      were received from 1336 employees (56% response rate). The outcome variable was
      mental distress, assessed with a shortened version of the Hopkins Symptom
      Checklist (HSCL-5). The following individual factors were adjusted for: age,
      gender, marital status, and shift work locus of control. Psychosocial work
      factors included: night work, demands, control and support, and shift work-home
      interference. RESULTS: The level of mental distress was higher among men than
      women. In the adjusted regression model, the following were associated with
      mental distress: (i) high scores on quantitative demands, (ii) low level of
      support, and (iii) high level of shift work-home interference. Psychosocial work
      factors explained 76% of the total explained variance (adjusted R (2)=0.21) in
      the final adjusted model. CONCLUSIONS: Psychosocial work factors, such as
      quantitative demands, support, and shift work-home interference were
      independently associated with mental distress. Shift schedules were only
      univariately associated with mental distress.

PMID- 21874210
TI  - Aspects on the research fields "from cell to society", clinical trials and
      research methodology, and report on impact.

PMID- 21874211
TI  - Towards a conceptual description of Physical and Rehabilitation Medicine.
AB  - Physical and Rehabilitation Medicine (PRM) is an independent medical specialty
      focusing on the improvement of functioning. A shared understanding of concepts is
      of vital importance for integrated action in this field. The aim of the present
      paper is to provide a conceptual model of PRM, to give background on its
      development and adoptions, and to explain the choice of terms, phrases, and
      concepts. It is based on the terms and concepts of the International
      Classification of Functioning, Disability and Health (ICF) that provides a widely
      accepted conceptual model and taxonomy of human functioning. Based on the White
      Book on Physical and Rehabilitation Medicine in Europe of 2006 a first proposal
      for a conceptual description of rehabilitation has been published in 2007. This
      proposal has been subjected to comments for modifications and amendments. E.g. it
      was underlined that PRM can apply both a health condition perspective including
      curative approaches and measures aiming at body functions and structures and a
      multi-dimensional and multi-professional team approach aiming to optimize
      functioning from a comprehensive functioning and disability perspective. The
      interaction between the PRM specialist and the person should be characterized as
      a partnership. PRM specialists work across all areas of health services and
      across all age groups. In summary, the specialty of PRM is characterized as the
      medicine of functioning.

PMID- 21874212
TI  - Predicting self-reported recovery one year after major road traffic accident
      trauma.
AB  - OBJECTIVE: The aim of this study was to examine the self-reported health status
      of road traffic accident victims and the predictors of self-assessed recovery 1
      year after major trauma in a French population. DESIGN: A follow-up study.
      METHODS: The cohort comprised 276 seriously injured victims of road traffic
      accidents, aged > 16 years from the Rhone administrative department, France.
      Victim characteristics at the time of the crash and self-reported health status 1
      year after trauma were collected. Predictive factors for self--assessed recovery
      were examined using a Poisson regression approach. RESULTS: The majority of
      victims were male (76%); most had severe injuries (76%), involving mainly the
      lower limbs and the head (68% and 55%, respectively). At 1-year follow-up, 80%
      reported being not fully recovered. Self-reported health status was not
      significantly associated with age, gender, being in employment, type of road
      user, or health status during the year preceding the accident, but rather with
      low socio-economic status, high injury severity, and presence of lower limb
      injury. CONCLUSION: Care for subjects who are at high risk of not fully
      recovering (manual workers, the very seriously injured, and those with lower limb
      injury) needs to be extended and improved. Longer follow-up studies on the risk
      factors for not fully recovering are needed in order to reduce harmful
      consequences for victims.

PMID- 21874213
TI  - Poor prognostic factors in complex regional pain syndrome 1: a Delphi survey.
AB  - OBJECTIVE: A major challenge in the management of patients with complex regional
      pain syndrome 1 is identifying those individuals who are at risk of developing
      severe problems. Data from large follow-up studies providing empirical evidence
      are largely lacking. The goal of this study was to obtain an expert-agreed
      priority list of parameters that are correlated with a poor prognosis. METHODS:
      In a two-round Delphi survey, experts were asked to list those parameters that
      they considered to be strongly associated with a poor prognosis (first round) and
      to weight parameters that they believed to be most relevant for poor prognosis
      (second round). Median ratings and interquartile ranges were calculated. Rates >
      7 and interquartile ranges < 3 depicted important and expert-agreed parameters.
      RESULTS: Thirty-nine experts compiled a list of 254 items. Twenty-eight experts
      reached a consensus on 49 important items associated with poor prognosis. They
      primarily agreed on clinical manifestations of complex regional pain syndrome 1.
      Psychosocial factors were considered less important. CONCLUSION: The findings of
      this study indicate that poor prognosis for complex regional pain syndrome 1 is
      primarily dependent on clinical manifestations. While evidence suggests that
      psychosocial factors may play a role in the development of the condition, their
      role in poor prognosis appears to be less important.

PMID- 21874214
TI  - Association of fear of movement and leisure-time physical activity among patients
      with chronic pain.
AB  - OBJECTIVE: The aim of this study was to clarify the association of fear of
      movement and physical activity among patients with chronic musculoskeletal pain.
      METHODS: The sample comprised 93 patients participating in a multidisciplinary
      pain management programme. The purpose of the programme was to regain overall
      functioning by means of physical and functional exercises, education and personal
      pain management training. Tampa Scale of Kinesio-phobia and Leisure Time Physical
      Activity questionnaires were completed at baseline, and at 6-month and 12-month
      follow-ups. RESULTS: At baseline, low and medium kinesiophobia groups showed more
      leisure-time physical activity than did the high kinesiophobia group (p = 0.024).
      At a 6-month follow-up the high kinesiophobia group had increased their physical
      activity index to the level of the low and medium kinesiophobia groups and
      maintained that change to 12-month follow-up. The effect sizes of the change in
      the physical activity index and pain intensity at the 12-month follow-up were
      both moderate (0.56) in the high kinesiophobia group. CONCLUSION: The change in
      physical activity and kinesiophobia was associated with the level of baseline
      kinesiophobia. Multidisciplinary rehabilitation seems to produce favourable
      effects in terms of physical activity and pain among the high kinesiophobia
      patients.

PMID- 21874215
TI  - Clinical benefits of the addition of lower extremity low-intensity resistance
      muscle training to early aerobic endurance training intervention in patients with
      coronary artery disease: a randomized controlled trial.
AB  - OBJECTIVE: Muscle resistance training is often combined with aerobic endurance
      training during rehabilitation of patients with coronary artery disease. However,
      the clinical effects of additional lower-extremity low-intensity muscle
      resistance training during early rehabilitation (within the first month after
      coronary revascularization) in patients with coronary artery disease remain
      unclear. DESIGN: Prospective randomized controlled trial. SUBJECTS: Sixty
      patients with coronary artery disease. METHODS: Subjects were randomly assigned
      to early aerobic endurance training (n = 30) or combined aerobic endurance and
      resistance muscle training (n = 30). Subjects performed 18 (standard deviation 2)
      exercise sessions (at 65% VO(2peak), for 40 mins/session). In resistance muscle
      training, additional low-intensity (12-20 repetition maximum) resistance muscle
      exercises were performed. The following parameters were evaluated: exercise
      capacity, body composition, blood lipid profile, glycaemic control, blood
      endothelial progenitor cell and cytokine content, and muscle performance.
      RESULTS: A total of 47 patients with coronary artery disease completed the
      intervention. Total body lean tissue mass tended to increase with greater
      magnitude (p = 0.07), and blood high-density lipid cholesterol content increased
      with significantly greater magnitude in resistance muscle training (p < 0.05),
      compared with aerobic endurance training. Maximal exercise capacity, ventilatory
      threshold, and muscle performance increased, and steady-state exercise
      respiratory exchange ratio, and adipose tissue mass reduced significantly (p <
      0.05), without differences between groups (p < 0.05). CONCLUSION: In early
      aerobic endurance training intervention in patients with coronary artery disease,
      additional low-intensity resistance muscle training contributes to a greater
      increase in blood high-density lipid cholesterol content, and tends to affect
      lean tissue mass.

PMID- 21874217
TI  - Are all melanomas dangerous?
AB  - The increased incidence of cutaneous malignant melanoma, together with only minor
      changes in mortality, has brought into question the existence of a melanoma
      epidemic. The discrepancy between incidence and mortality suggests that most
      newly diagnosed melanomas have indolent behaviour. This review summarizes the
      most recent epidemiological findings regarding the incidence of cutaneous
      malignant melanoma, mortality, Breslow thickness and clinical stage. Studies
      published between 2005 and 2010 with more than 2,000 test subjects were included
      in this review. These studies all report an increase in incidence of melanoma
      during the last few decades, with by far the highest increase in tumours at a
      very early stage (T1 or IA). Little or no change was seen in mortality. However,
      increases in both mortality and incidence of thick melanomas were found in the
      oldest subgroups, especially in men. These findings indicate the existence of a
      certain degree of overdiagnosis of melanoma. They also indicate the existence of
      two different types of epidemic, for younger and older subgroups.

PMID- 21874218
TI  - Validation of a model of itch induction for brain positron emission tomography
      studies using histamine iontophoresis.
AB  - Skin-brain signalling in itch reactions has been demonstrated with neuroimaging
      techniques showing specific brain activation. With positron emission tomography
      (PET), the itch model used must be adapted to technical and practical
      constraints. The technique of itch induction by histamine iontophoresis enables
      modulation of the sensation via the electrical charge applied. This itch model
      was validated on normal forearm skin of 56 subjects, with itch visual analogue
      scores peaking to approximately 1.0 cm after 3-4 min, falling to 0.2 cm at 15
      min, with no influence of sex, zone, or order. Subsequently, the model was used
      in a PET study on 14 male volunteers, comparing histamine with physiological
      saline (control). The results show that the brain is able to discriminate these
      two conditions, with activated areas similar to those described previously, with,
      in addition, the anterior cingulate cortex and the insula being positively
      correlated with the intensity of the sensation.

PMID- 21874219
TI  - Validation of self-testing as a method to estimate the prevalence of nickel
      allergy.
AB  - The aim of this study was to investigate the validity of self-patch testing for
      nickel allergy, in order to determine a cost-effective method for surveillance of
      the prevalence of nickel allergy. Population-based study including patch testing
      is the most reliable method to study the prevalence of allergy, but it is
      expensive and has logistical problems. A total of 191 dermatology patients
      referred to patch testing were provided with a self-test package with written
      instructions. The self-test was applied on the arm by the patient, on the same
      day that the regular patch test was applied on the back. The patient evaluated
      the self-test before patch test reading at the clinic. Patch test at the
      dermatology clinic detected 46/191 (24%) nickel-positive individuals. The
      sensitivity of the self-test was 72% (95% confidence interval (CI) 57-84), the
      specificity 91% (95% CI 85-95), and the proportion of agreement 86% (95% CI 81
      91). Thus, in the population studied, the validity of self-testing for nickel
      allergy was adequate.

PMID- 21874220
TI  - Onychomycosis: first case due to Aspergillus nomius.

PMID- 21874221
TI  - Abstracts of the 6th World Congress of Itch 2011. September 4-6, 2011. Brest,
      France.

PMID- 21874222
TI  - Multidrug resistance-associated protein 3 and Bcl-2 contribute to multidrug
      resistance by vinorelbine in lung adenocarcinoma.
AB  - Although cancer cells initially respond to vinorelbine (NVB), the acquisition of
      resistance to the treatment is the main cause of chemotherapeutic failure in lung
      cancer. The intrinsic mechanism of drug resistance induced by NVB in lung cancer
      is not clear and tumor cell models to study NVB resistance have not been widely
      studied. We previously established a NVB resistant cell line, Anip973/NVB,
      derived from the Anip973 lung adenocarcinoma cell line. The aim of this study was
      to investigate the molecular mechanisms involved in the resistance to NVB in lung
      adenocarcinoma. Genetic profiles of Anip973/NVB and Anip973 cells were compared
      by microarray analysis and qRT-PCR. Tumor xenografts were obtained by grafting
      Anip973/NVB and Anip973 cells into nude mice and the xenograft response to NVB or
      control treatment was evaluated. Morphological assessment of xenograft tissues
      was performed by transmission electron microscopy (TEM). Immunohistochemistry
      (IHC) was used to compare Bcl-2 and MRP3 protein expression in xenografts. Fifty
      five up-regulated genes and 88 down-regulated genes in Anip973/NVB cells compared
      with Anip973 cells were identified by cDNA microarray analysis. Up-regulation of
      MRP3 and Bcl-2 was confirmed by qRT-PCR. NVB inhibits xenografts of Anip973
      growth but did not affect xenografts of Anip973/NVB growth. Ultrastructural
      changes observed by TEM showed that NVB induces apoptosis in the Anip973-treated
      group but not in the Anip973/NVB-treated group. Higher expression rates of Bcl-2
      and MRP3 were observed in Anip973/NVB xenograft cells compared with Anip973
      xenograft cells by IHC. In conclusion, in the present study, we identified a set
      of genes responsible for multidrug resistance in Anip973/NVB cells. Among them,
      MRP3 and Bcl-2 may participate in lung adenocarcinoma multidrug resistance
      induced by NVB.

PMID- 21874223
TI  - Zanthoxylum avicennae extracts induce cell apoptosis through protein phosphatase
      2A activation in HA22T human hepatocellular carcinoma cells and block tumor
      growth in xenografted nude mice.
AB  - The use of herbs as alternative cancer therapies has attracted a great deal of
      attention owing to their lower toxicity. Whether Zanthoxylum avicennae (Ying Bu
      Bo, YBB) induces liver cancer cell apoptosis remains unclear. In this study, we
      investigated the effect of YBB extracts (YBBEs) on HA22T human hepatocellular
      carcinoma cells in vitro and in an in vivo mouse xenograft model. HA22T cells
      were treated with different concentrations of YBBEs and analyzed with Western
      blot analysis, TUNEL, JC-1 staining and siRNA transfection assays. Additionally,
      the HA22T-implanted xenograft nude mice model was applied to confirm the cellular
      effects. YBBEs-induced apoptosis, up-regulated death receptor apoptotic pathway
      markers as well as mitochondrial proteins, and suppressed the survival proteins
      in a dose-dependent manner. Pro-survival Bcl-2 family proteins were inhibited and
      the pro-apoptotic ones were increased. Protein phosphatase 2A (PP2A) siRNA or
      okadaic acid reversed the YBBEs effects, confirming the role of PP2A in YBBEs
      induced HA22T apoptosis. All our experimental evidence indicates that YBBEs
      significantly promote HA22T apoptosis and reduce tumor sizes in xenograft nude
      mice via PP2A in a dose-dependent manner.

PMID- 21874224
TI  - The metabolic syndrome of fructose-fed rats: effects of long-chain
      polyunsaturated omega3 and omega6 fatty acids. I. Intraperitoneal glucose
      tolerance test.
AB  - The present series of experiments aim mainly at investigating the possible
      influence of changes in the com-position of dietary lipids (sunflower oil, salmon
      oil, safflower oil) upon the metabolic syndrome found in rats exposed to a
      fructose-rich diet. For purpose of comparison, a control group of rats received
      the sunflower oil diet with substitution of fructose by starch. An
      intraperitoneal glucose tolerance test, performed after overnight starvation
      fifty days after the start of the experiments at the 6th week after birth,
      indicated, as expected, impaired tolerance to glucose and deterioration of
      insulin sensitivity (HOMA index), without changes in the insulinogenic index,
      when comparing the fructose-fed rats to the starch-fed rats both exposed to the
      sunflower oil diet. In the fructose-fed rats, enrichment of the diet by long
      chain polyunsaturated omega3 fatty acids supplied by salmon oil, a modest
      improvement of insulin sensitivity was opposed, in term of glucose homeostasis,
      by a decreased secretory response to glucose of insulin-producing cells. Last, in
      the fructose-fed rats, the partial substitution of sunflower oil by safflower oil
      rich in long-chain polyunsaturated omega6 fatty acids further deteriorated
      glucose homeostasis, with a higher mean HOMA index and a severe decrease of the
      insulinogenic index. These findings justify further investigations on such items
      as the time course for changes in metabolic and hormonal variables and both the
      metabolic and secretory responses of isolated pancreatic islets to selected
      nutrient secretagogues.

PMID- 21874225
TI  - Expression and characterization of recombinant human milk fat globule-EGF factor
      VIII.
AB  - Apoptosis plays an important role in the patho-biology of sepsis. The opsonizing
      protein milk fat globule-EGF factor VIII (MFG-E8) is involved in apoptotic cell
      clearance. Our previous studies have shown that administration of rat MFG-E8
      containing exosomes or recombinant murine MFG-E8 (rmMFG-E8) is protective in a
      rat model of sepsis induced by cecal ligation of puncture (CLP). However, one
      obstacle hampering the development of MFG-E8 as a therapeutic agent for septic
      patients is the potential immunogenicity of animal proteins in humans. The
      purpose of this study, therefore, was to express recombinant human MFG-E8 (rhMFG
      E8) and characterize its biological activity. Using an E. coli system, we
      successfully expressed and purified the mature molecule of human MFG-E8 (Leu24
      Cys387). The purity of rhMFG-E8 was over 99% and it was immunoreactive for
      specific anti-human MFG-E8 antibodies. Amino acid sequence analysis by LC-MS/MS
      identified the purified protein as human MFG-E8. Using primary rat peritoneal
      macrophages, we showed that rhMFG-E8 markedly increased peritoneal macrophage
      phagocytosis of apoptotic thymocytes, which was as effective as commercial rmMFG
      E8. To determine the biological activity of rhMFG-E8 in vivo, male adult rats
      were subjected to sepsis by CLP. rhMFG-E8 or rmMFG-E8 were administered
      intravenously at the time of CLP. Our results demonstrated that both rhMFG-E8 and
      rmMFG-E8 reduced thymocyte apoptosis and plasma levels of lactate and IL-6 at 20
      h after CLP, and improved the 10-day survival rate. Thus, we have successfully
      expressed and purified biologically active rhMFG-E8. Our newly-expressed rhMFG-E8
      is highly effective in the rat model of sepsis.

PMID- 21874226
TI  - Novel GATA4 mutations in lone atrial fibrillation.
AB  - Atrial fibrillation (AF) is the most frequent cardiac arrhythmia and is a major
      cause of morbidity and mortality. Previous studies have established genetic
      defects as a risk factor for AF in a minority of patients. However, AF is of
      substantial genetic heterogeneity and the molecular determinants for AF in a
      majority of cases remain unclear. In this study, the entire coding sequence and
      splice junctions of GATA4, which encodes a zinc-finger transcription factor
      essential for cardiogenesis, were sequenced in 160 unrelated patients with lone
      AF. A total of 200 unrelated ethnically matched healthy individuals were used as
      controls. The available relatives of the patient carrying an identified mutation
      were genotyped. The functional characteristics of the mutant GATA4 were analyzed
      using a luciferase reporter assay system. As a result, two novel heterozygous
      GATA4 mutations of p.G16C and p.H28D, were identified in 2 unrelated families
      with AF, respectively, which co-segregated with AF in each family with complete
      penetrance. Functional analysis demonstrated that the mutations of GATA4 were
      associated with a significantly decreased transcriptional activity. The findings
      expand the mutation spectrum of GATA4 linked to AF and provide novel insight into
      the molecular mechanism involved in the pathogenesis of AF.

PMID- 21874227
TI  - Activation of the delta-opioid receptor inhibits serum deprivation-induced
      apoptosis of human liver cells via the activation of PKC and the mitochondrial
      pathway.
AB  - Apoptosis of human liver cells is commonly found in liver diseases and liver
      surgery and directly affects their prognosis. Recent studies have found that
      delta-opioid receptors, abundant in the membranes of hepatic cells, participate
      in the oncogenesis and progression of liver tumors, viral hepatitis, liver
      cirrhosis and other diseases. The purpose of this study was to analyze the effect
      of the activation of the delta-opioid receptor on liver cell apoptosis and
      explore its relationship with PKC and the mitochondrial pathway. Hepatic cells
      were serum-deprived to induce apoptosis in vitro. During the period of apoptosis,
      mitochondrial membrane potential decreased, protein levels of cytosolic
      cytochrome c increased and the expression of Bcl-2 decreased, indicating that
      apoptosis was specifically induced by the mitochondrial pathway. Importantly,
      activation of delta-opioid receptors reversed the apoptotic state of hepatic
      cells. Following delta-opioid receptor activation, the mitochondrial membrane
      potential remained stable, and the expression of cytosolic cytochrome c and Bax
      decreased. These data suggest that delta-opioid receptor activation specifically
      inhibits the mitochondrial apoptotic pathway. In addition, activation of the
      delta-opioid receptor apparently increased the levels of PKC; blocking the PKC
      pathway led to increased apoptosis of liver cells, which was not affected by the
      activation of delta-opioid receptor. Blocking the PKC pathway led to increased
      apoptosis of liver cells, which was associated with delta-opioid receptor
      activation. Therefore, the PKC pathway is involved in the anti-apoptotic effects
      of the delta-opioid receptor on liver cells.

PMID- 21874228
TI  - Genome-wide copy number profiling using a 100K SNP array reveals novel disease
      related genes BORIS and TSHZ1 in juvenile angiofibroma.
AB  - Juvenile angiofibroma (JA) is a unique fibrovascular tumor, which is almost
      exclusively found in the posterior nasal cavity of adolescent males. Although
      histologically classified as benign, the tumor often shows an aggressive growth
      pattern and has been associated with chromosomal imbalances, amplification of
      oncogenes and epigenetic dysregulation. We present the first genome-wide
      profiling of JAs (n=14) with a 100K single nucleotide polymorphism (SNP)
      microarray. Among the 30 novel JA-specific amplifications detected on autosomal
      chromosomes with this technique, the genes encoding the cancer-testis antigen
      BORIS (brother of the regulator of imprinted sites) and the developmental
      regulator protein TSHZ1 (teashirt zinc finger homeobox 1) were selected for
      further analysis. Gains for both BORIS (20q13.3) and TSHZ1 (18q22.3) were
      confirmed by quantitative genomic PCR. Furthermore, quantitative RT-PCR revealed
      a significant up-regulation of BORIS (p<0.001) and TSHZ1 transcripts (p<0.05) for
      JAs compared to nasal mucosa. Following detection of BORIS and TSHZ1 proteins in
      western blots of JAs, subcellular localization was determined for both proteins
      in immunostaining of JA cryosections. In conclusion, genomic copy number
      profiling using an SNP microarray has been proven to be a suitable and reliable
      tool for identifying novel disease-related genes in JAs and newly implicates
      BORIS and TSHZ1 overexpression in the pathogenesis of JAs. Detection of BORIS in
      JAs is described with special regard to tumor proliferation and epigenetic
      dysregulation, and the finding of TSHZ1 amplifications is discussed with special
      respect to the hypothesis of JAs as malformations of the first branchial arch
      artery.

PMID- 21874229
TI  - Simvastatin reduces tumor cell adhesion to human peritoneal mesothelial cells by
      decreased expression of VCAM-1 and beta1 integrin.
AB  - Peritoneal carcinomatosis describes cancer metastasis onto the surface of the
      peritoneum. It is frequently caused by ovarian and colorectal cancer. Once a
      tumor has penetrated the peritoneum, cancer cells disseminate into the abdominal
      cavity. Additionally, surgery can account for the spread of free tumor cells.
      Their subsequent adhesion to mesothelial cells (HMCs) initiates peritoneal
      carcinomatosis. Therefore, this study analyzed the effect of simvastatin on tumor
      cell adherence. HMCs were isolated from human greater omentum. Fluorescence
      labeled tumor cells (SKOV-3, OvCar-29, OAW42, FraWu; ovarian/HT29; colorectal)
      were incubated on confluent mesothelial monolayers with 10 uM simvastatin for 48
      h. Adhesion was quantified using a fluorescence reader. Expression of the
      adhesion molecules VCAM-1, ICAM-1 and beta1 integrin chain under the influence of
      simvastatin 0.1-100 uM for 24-72 h was analyzed using flow cytometry. Simvastatin
      significantly reduced the adhesion of all ovarian cancer cells and HT29 to HMCs
      (P<=0.001). Concomitantly simvastatin decreased the expression of VCAM-1 on HMCs.
      ICAM-1 and beta1 integrin chain expression on ovarian cancer cells was also
      clearly reduced. By contrast, the expression of the analyzed adhesion molecules
      on HT29 cells remained unchanged. Simvastatin clearly inhibits tumor cell
      adhesion to HMCs. In the case of ovarian cancer cell lines it appears to be
      mediated by decreased expression of both VCAM-1 on HMCs and the integrin
      alpha4beta1 on tumor cells. As an example of adhesion molecule down-regulating
      drugs, simvastatin may provide a novel therapeutic approach to the prevention of
      peritoneal carcinomatosis.

PMID- 21874230
TI  - Anti-tumor activity of fucoidan is mediated by nitric oxide released from
      macrophages.
AB  - Fucoidan, a sulfated polysaccharide, has significant cytotoxic activity against
      tumor cells; however, the mechanism(s) of this action remains poorly understood.
      The present study was designed to determine the in vitro and in vivo effects of
      fucoidan and their molecular mechanisms. Fucoidan from Cladosiphon okamuranus
      Tokida cultivated in Okinawa, Japan, delayed tumor growth in Sarcoma 180 (S-180)
      bearing mice. However, it failed to inhibit S-180 cell growth in vitro. Activated
      macrophages are known to have anti-tumor effects. Murine RAW264.7 macrophages
      stimulated with fucoidan exerted cytotoxicity towards S-180 cells in vitro. This
      cytotoxicity was associated with nitric oxide (NO) production. Both cytocidal
      effect and NO production were significantly inhibited by L-NAME, an inhibitor of
      NO synthase (NOS). Furthermore, activation of nuclear factor-kappaB was a key
      step in the transcriptional activation of the inducible NOS gene. Taken together,
      our results indicate that the anti-tumor activity of fucoidan on S-180 cells is
      mediated through increased NO production by fucoidan-stimulated macrophages via
      nuclear factor-kappaB-dependent signaling pathway.

PMID- 21874231
TI  - Decreased accumulation of immune regulatory cells is correlated to the antitumor
      effect of IFN-gamma overexpression in the tumor.
AB  - During mammary tumorigenesis, there is a profound tumor-induced immunosuppression
      and a progressive thymic atrophy associated with tumor development. IFN-gamma has
      been shown to be effective in enhancing antitumor responses in several tumor
      models, however, how IFN-gamma exerts its anti-tumor effect is largely
      controversial. In the present study we have used a mammary tumor model to
      investigate whether the levels of IFN-gamma have an important role in the tumor
      induced immuno-suppression as well as in the pathogenesis of the thymic atrophy.
      We evaluated this possibility using DA-3 cells transfected to express IFN-gamma
      (DA-3/IFN-gamma), a system that provides constant, local production of IFN-gamma
      within the tumor microenvironment. Overexpression of IFN-gamma in the mammary
      tumor results in a marked delay of tumor growth, a reduction in regulatory T
      cells and myeloid-derived suppressor cells accumulation mostly due to down
      regulation of chemokines implicated in the recruitment of immune regulatory
      cells, and a blockage in the tumor-associated thymus atrophy. Collectively, our
      data suggest that the replacement of the faulty levels of IFN-gamma in the tumor
      results in a diminution of the tumor-induced immune suppression caused by the
      mammary tumor development.

PMID- 21874232
TI  - Prognostic impact of p53 aberrations for R-CHOP-treated patients with diffuse
      large B-cell lymphoma.
AB  - Diffuse large B-cell lymphoma (DLBCL) is the most frequent lymphoma in adults.
      There are specific alterations that appear repeatedly in DLBCL cases and play a
      role in lymphomagenesis or progression of the disease. Some aberrations were used
      as prognostic markers in the pre-rituximab era. Addition of rituximab to the
      classical anthracycline-based chemotherapy significantly increased the survival
      rate in DLBCL. Only few prognostic factors have been re-evaluated for patients
      treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and
      prednisone). We performed complex analysis of the p53 tumor suppressor in
      collection of 75 DLBCL cases. Fifty-four patients were de novo cases, twenty-one
      cases developed into DLBCL by transformation from less aggressive disease. We
      determined functional status by analysis of separated alleles in yeast (FASAY)
      and analyzed the p53 mutations by cDNA sequencing. We assessed the level of the
      p53 protein by immunoblot analysis. We used FISH to analyze loss of the p53 and
      ATM (ataxia telangiectasia mutated) gene deletions. We detected 16 p53 mutations
      (21.3%) including the mutation activating non-sense-mediated RNA decay pathway.
      Deletion of the p53 allele was more common in cases with p53 mutation. Mutations
      and/or deletions of p53 had statistically significant negative impact on
      progression-free survival and tended to decrease also overall survival in 46 de
      novo DLBCL patients treated with R-CHOP. p53 aberrations are negative predictors
      for survival of DLBCL patients treated with R-CHOP.

PMID- 21874233
TI  - Regional therapy with DTA-H19 vector suppresses growth of colon adenocarcinoma
      metastases in the rat liver.
AB  - Curative surgery is possible in barely 10% of patients with colorectal liver
      metastases and combined treatment modalities scarcely improve survival in this
      group of patients. Hence, investigations of new therapeutic modalities are
      crucial. Overexpression of the H19 gene in liver metastases points to H19 as a
      target for cancer gene therapy. Here we have evaluated the possibility of
      regional intra-arterial treatment of liver meta-stases with the DTA-H19 plasmid.
      Intra-arterial treatment of a total dose of 2.5 mg (repeated injections of 500 ug
      DTA-H19 plasmid each dose after the first injection of 1000 ug) caused a
      significant delay in the tumor growth compared to control group. All of the
      tumors treated with the control vector increased in size, whereas 35.7% of the
      tumors in the groups treated with a total amount of 2.5 mg DTA-H19 plasmid shrank
      in size. The present study showed that the DTA-H19 plasmid administered intra
      arterially significantly delayed the tumor growth and even resulted in tumor
      regression in high percentage of the treated animals with liver metastases of
      colon cancer. Since human liver metastases demonstrated overexpression of the H19
      gene, regional administration of the plasmid seems to be a promising therapeutic
      approach.

PMID- 21874234
TI  - Identification of genes involved in radioresistance of nasopharyngeal carcinoma
      by integrating gene ontology and protein-protein interaction networks.
AB  - Radioresistance remains one of the important factors in relapse and metastasis of
      nasopharyngeal carcinoma. Thus, it is imperative to identify genes involved in
      radioresistance and explore the underlying biological processes in the
      development of radioresistance. In this study, we used cDNA microarrays to select
      differential genes between radioresistant CNE-2R and parental CNE-2 cell lines.
      One hundred and eighty-three significantly differentially expressed genes
      (p<0.05) were identified, of which 138 genes were upregulated and 45 genes were
      downregulated in CNE-2R. We further employed publicly available bioinformatics
      related software, such as GOEAST and STRING to examine the relationship among
      differentially expressed genes. The results show that these genes were involved
      in type I interferon-mediated signaling pathway biological processes; the nodes
      tended to have high connectivity with the EGFR pathway, IFN-related pathways, NF
      kappaB. The node STAT1 has high connectivity with other nodes in the protein
      protein interaction (PPI) networks. Finally, the reliability of microarray data
      was validated for selected genes by semi-quantitative RT-PCR and Western
      blotting. The results were consistent with the microarray data. Our study
      suggests that microarrays combined with gene ontology and protein interaction
      networks have great value in the identification of genes of radioresistance in
      nasopharyngeal carcinoma; genes involved in several biological processes and
      protein interaction networks may be relevant to NPC radioresistance; in
      particular, the verified genes CCL5, STAT1-alpha, STAT2 and GSTP1 may become
      potential biomarkers for predicting NPC response to radiotherapy.

PMID- 21874235
TI  - Identification of RHOXF2 (PEPP2) as a cancer-promoting gene by expression
      cloning.
AB  - Multiple mutations contribute to establish cancers. We have searched for
      potential oncogenes by screening cDNA libraries derived from gastric cancer cell
      lines, pancreatic cancer cell lines and glioma cell lines, using retrovirus
      mediated expression cloning. Two types of interleukin-3 (IL-3)-dependent cell
      lines, Ba/F3 and HF6, were transduced with the cDNA libraries and several genes
      that render these cells factor-independent were identified including PIM-1, PIM
      2, PIM-3, GADD45B and reproductive homeobox genes on the X chromosome gene F2
      (RHOXF2). Although no mutation in these genes was found, these molecules were
      highly expressed in cancer cell lines and they may play important roles in cell
      transformation. Among them, we focused on a transcriptional repressor RHOXF2.
      Transduction of RHOXF2 rendered HF6 cells factor-independent, while knockdown of
      RHOXF2 inhibited growth of the HGC27 gastric cancer cell line which highly
      expresses RHOXF2. In addition, RHOXF2-transduced HF6 cells quickly induced
      leukemia when transplanted into sublethally irradiated mice. Moreover, RHOXF2 is
      highly expressed in some leukemia cell lines and a variety of human cancer
      samples including colon and lung cancers. Thus, these results indicate that
      RHOXF2 is involved in carcinogenesis.

PMID- 21874236
TI  - mTHPC-based photodynamic therapy induction of autophagy and apoptosis in cultured
      cells in relation to mitochondria and endoplasmic reticulum stress.
AB  - Photodynamic therapy (PDT), an approved anticancer treatment, is reported as a
      potent inducer of programmed cell death (PCD) by both apoptosis and autophagy.
      The present study investigated the kinetics of both autophagy and caspase
      activation in MCF-7 cells submitted to mTHPC-PDT upon condition of treatment
      promoting ER accumulation of mTHPC. Fluence-dependent immediate cytochrome c (cyt
      C) release followed by caspase-9 and -7 activation at 1 h post-PDT evidenced a
      mitochondrial oxidative stress triggered by high light doses leading to >90% of
      cell death. ER oxidative stress was monitored by the induction of the glucose
      related protein chaperone GRP78. From 6 h post-PDT, GRP78 induction was
      accompanied by the conversion of LC3-I into LC3-II, the hallmark of autophagosome
      formation. The formation of acid vesicles evidenced by fluorescence microscopy
      was obvious from 22 h post-PDT. Twenty-four hours post-PDT, cyt C release
      decreased and caspase-9 cleavage disappeared, while the expression of cleaved
      caspase-7 remained significant. At the same time, the profiles of GRP78, cleaved
      caspase-7 and LC3-II expression were similar irrespective of light doses. In
      contrast to an inhibitor of caspase activation Z-VAD-FMK, the use of autophagy
      inhibitor, Wortmannin, impaired cytotoxicity along with an increase in caspase-7
      activation. These results demonstrate a valuable contribution of autophagy to
      cell death in mTHPC-photosensitized MCF-7 cells.

PMID- 21874237
TI  - Nutritional improvement of metabolic syndrome parameters in immature fructose-fed
      wild-type mice.
AB  - The incidence of type 2 diabetes mellitus is on the increase worldwide, with both
      environmental and genetic factors implicated in its development. Diabetes is
      often preceded by metabolic syndrome (MS) and may develop in normal adults
      ingesting a high fructose diet. The effect of high fructose intake on the
      development of MS in children and adolescents is less clear. Our objective was to
      study the effects of a nutrient mixture and metformin (MET), a widely used oral
      diabetic medication, in modulating the physiological and biochemical parameters
      of a high fructose diet in immature mice. C57BL/6J wild-type mice aged 7 weeks
      were administered 12% fructose in their water and MET in distilled water or a
      diabetic nutrient mix (DNM) over 7 weeks. DNM-fed mice showed a decrease in
      systolic blood pressure, total cholesterol and fructosamine compared to the
      fructose-fed only group (p<0.05). A discordant result was observed in the MET
      group, with a decrease in blood pressure but increases in total cholesterol and
      fructosamine (p<0.05). Serum glucose did not change significantly among the
      groups. Thus, symptoms of fructose-induced MS in young mice could be countered
      nutritionally. Additionally, MET may improve certain biochemical markers while
      worsening others.

PMID- 21874238
TI  - NM_001013649.3 gene is down-regulated in human colorectal adenocarcinoma.
AB  - The present study aimed to evaluate the expression of NM_001013649.3 in human
      colorectal adenocarcinoma tissue and its correlation with clinicopathological
      aspects of the disease. Through the combination of a cDNA subtractive library and
      cDNA microarray analysis, a differentially expressed sequence tag ES274081 was
      identified whose full-length cDNA sequence (NM_001013649.3) was obtained through
      BLASTn analysis on NCBI. Reverse transcription quantitative real-time PCR was
      used to assess the expression levels of NM_001013649.3 in cancer and adjacent
      normal colorectal tissues from 30 patients with colorectal adenocarcinoma. The
      mRNA levels of NM_001013649.3 were significantly lower in the cancer tissues
      compared to the adjacent normal colorectal tissues of 25 out of 30 (83%) patients
      (p<0.005). Furthermore, the rate of down-regulation was significantly higher in
      moderately differentiated samples (21 out of 23; 91%) compared to poorly
      differentiated samples (3 out of 6; 50%) (p<0.05). The mRNA levels of
      NM_001013649.3 are significantly down-regulated in colorectal adenocarcinoma
      tissue, and this down-regulation is most likely correlated with the
      differentiation status of the cancer, indicating that NM_001013649.3 is
      potentially involved in the pathogenesis of colorectal adenocarcinoma.

PMID- 21874239
TI  - Zinc finger protein HZF1 promotes K562 cell proliferation by interacting with and
      inhibiting INCA1.
AB  - Previously, we characterized a zinc finger protein gene HZF1 (ZNF16) and
      demonstrated that it played a significant role in the erythroid and
      megakaryocytic differentiation of K562 cells by knockdown of the gene. In this
      study, we examined the effect of HZF1 on the proliferation and apoptosis of K562
      cells and identified the possible mechanism for this effect. By lentivirus
      mediated gene transfer, we obtained stable K562 transductants with HZF1
      overexpression (K562/WPXL-HZF1) and stable control transductants (K562/WPXL).
      Significantly rapid cell amplification was observed in K562/WPXL-HZF1 cells
      compared to K562/WPXL cells. The cell cycles of the two transductants were
      analyzed and the results demonstrated that HZF1 overexpression promoted the S to
      G2/M phase transition. Additionally, we found that the overexpression of HZF1
      slightly inhibits the apoptosis of K562 cells induced by sodium arsenate.
      Furthermore, using a yeast two-hybrid (Y2H) system we identified the HZF1
      interacting proteins and screened 29 potential binding partners of HZF1. Using a
      co-immunoprecipitation (Co-IP) assay, we confirmed the interaction between HZF1
      and the inhibitor of cyclin-dependent kinase (CDK) interacting with cyclin A1
      (INCA1), and proved that this interaction leads to the inhibition of INCA1
      function, which rescued the activity of CDK2 inhibited by INCA1. In conclusion,
      our results identified novel functions of the HZF1 gene and revealed a possible
      mechanism through which HZF1 affects K562 cell proliferation.

PMID- 21874240
TI  - Molecular cloning and tissue distribution of a Schistosoma japonicum gene
      encoding AMY-1.
AB  - It is well known that the mammalian associate of Myc-1 (AMY-1) plays a
      significant role in spermatogenesis or cellular differentiation. A full-length
      complementary DNA (cDNA) encoding AMY-1 of Schistosoma japonicum (SjAMY-1) was
      identified and isolated from a cDNA library. The gene contained an open reading
      frame of 315 nucleotides, encoding 105 amino acids. Sequence analysis showed that
      SjAMY-1 shares 65.7% homology with Homo sapiens AMY-1 amino acids and contains a
      conserved domain from the AMY-1 family. In this study, we cloned and expressed a
      recombinant SjAMY-1 (rSjAMY-1) with a molecular size of 14 kDa. The native SjAMY
      1 in soluble worm antigen was identified by anti-rSjAMY-1 sera in the Western
      blot analysis, which demonstrated the presence of this protein in the parasite.
      Immunofluorescence studies indicated a localization of SjAMY-1 in various tissues
      and organs including the tegument and subtegumental muscles in adult worms, the
      ventral sucker in cercariae and the internal structures of eggs. Given the key
      roles of mammalian AMY-1 in cell proliferation and differentiation, the
      characterization of SjAMY-1 may allow for a better understanding of the
      development of S. japonicum.

PMID- 21874241
TI  - MALDI mass spectrometry imaging in oncology (Review).
AB  - Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging
      (MSI) has improved over the years and is increasingly being used for biomarker
      discovery directly from human tissue sections. State-of-the-art technology
      currently enables a resolution down to 20 um. MSI therefore allows the
      correlation of spatial and temporal protein expression profiles with distinct
      morphological features without requiring target-specific reagents, such as
      antibodies. Several studies have demonstrated the strength of the technology for
      uncovering new markers that correlate with disease severity as well as prognosis
      and therapeutic response. This review provides an overview of MALDI imaging
      functionality and its advantages and disadvantages, and provides a current
      literature overview of malignancy-based biomarker detection. Further improvements
      on instrumentation sensitivity, image processing and sample preparation will
      enable the detection of novel, tissue-specific biomarkers. However, emphasis
      should be given to large validation studies and/or subsequent identification of
      differentially observed protein peaks in order to transfer MSI protein profiling
      and/or novel biomarkers thereof into clinical use.

PMID- 21874242
TI  - Investigation of vasculogenic mimicry in intracranial hemangiopericytoma.
AB  - Vasculogenic mimicry (VM) has increasingly been recognized as a form of
      angiogenesis. Previous studies have shown that the existence of VM is associated
      with poor clinical prognosis in certain malignant tumors. However, whether VM is
      present and clinically significant in intracranial hemangiopericytoma (HPC) is
      unknown. The present study was therefore designed to examine the expression of VM
      in intracranial HPC and its correlation with matrix metalloprotease-2 (MMP-2) and
      vascular endothelial growth factor (VEGF). A total of 17 intracranial HPC
      samples, along with complete clinical and pathological data, were collected for
      our study. Immunohistochemistry was performed to stain tissue sections for CD34,
      periodic acid-Schiff, VEGF and MMP-2. The levels of VEGF and MMP-2 were compared
      between tumor samples with and without VM. The results showed that VM existed in
      12 of 17 (70.6%) intracranial HPC samples. The presence of VM in tumors was
      associated with tumor recurrence (P<0.05) and expression of MMP-2 (P<0.05).
      However, there was no difference in the expression of VEGF between groups with
      and without VM.

PMID- 21874243
TI  - Anti-obesity effects of Geranium thunbergii extract via improvement of lipid
      metabolism in high-fat diet-induced obese mice.
AB  - This study investigated the anti-obesity properties of an extract of Geranium
      thunbergii (GTE) in high-fat diet-induced obese mice. GTE treatment significantly
      reduced body weight, adipose tissue mass, adipocyte size, as well as serum
      triglyceride, total cholesterol and low-density lipoprotein-cholesterol levels in
      obese mice compared to high-fat diet-fed mice. It also decreased serum leptin
      levels and increased adiponectin levels. The serum levels of aspartate
      transaminase, alanine transaminase, blood urea nitrogen and creatinine were not
      significantly changed in GTE-treated mice compared to serum levels in normal diet
      and high-fat diet-fed mice. Furthermore, GTE suppressed the mRNA levels of sterol
      regulatory element-binding protein 1c, peroxisome proliferator-activated receptor
      gamma, adipocyte fatty acid-binding protein and fatty acid synthase in the
      adipose tissues of obese mice. These results suggest that GTE ameliorated high
      fat diet-induced obesity by altering the adipokine levels and downregulating the
      expression of transcription factors and lipogenic enzymes involved in lipid
      metabolism.

PMID- 21874244
TI  - regulation of the invasion and metastasis of human glioma cells by polypeptide N
      acetylgalactosaminyltransferase 2.
AB  - Polypeptide, N-acetylgalactosaminyltransferase 2 (ppGalNAc-T2), is a member of
      the ppGalNAcT family which is the initial glycosyltransferase in O-glycan
      synthesis. Our previous studies have demonstrated that ppGalNAc-T2 plays a vital
      role in the process of tumor emergence and development. In this study, we aimed
      to determine whether ppGalNAc-T2 is correlated with the invasion and metastasis
      of human glioma cells. PpGalNAc-T2 sense vectors and interference vectors
      constructed in our laboratory were successfully transfected into SHG44 and U251
      cells, which were observed through fluorescence microscopy, RT-PCR and western
      blot analysis. The metastasis of U251 cells was determined using a wound healing
      assay, and ppGalNAc-T2 was found to inhibit cell migration. By RT-PCR, glioma
      cell invasion assay showed that the expression of MMP-2 was increased in ppGalNAc
      T2-knockdown cells, while the expression of MMP-9 and TGF-beta1 was decreased in
      ppGalNAc-T2-overexpressing cells at the mRNA level. Meanwhile, the expression of
      TIMP-2 at the mRNA level was contrary to MMP-2. In summary, our findings indicate
      that ppGalNAc-T2 plays a poten-tial role in glioma cell migration and invasion,
      suggesting a new molecular therapeutic target for human malignant glioma
      treatment.

PMID- 21874245
TI  - Cyclooxygenase mediates cardioprotection of angiotensin-(1-7) against
      ischemia/reperfusion-induced injury through the inhibition of oxidative stress.
AB  - Angiotensin (Ang)-(1-7) exhibits cardioprotective effects in myocardial ischemia
      reperfusion (I/?R)-induced injury. However, the roles of oxidation and
      cyclooxygenase (COX) in the cardioprotection of Ang-(1-7) remain unclear. This
      study was conducted to investigate whether oxidation and COX were involved in the
      cardioprotection of Ang-(1-7) against I/?R-induced injury in isolated rat hearts.
      The hearts were subjected to 15 min regional ischemia followed by 30 min
      reperfusion. Myocardial I/?R treatment induced significant cardiac dysfunction,
      including ventricular arrhythmia (VA) and a reduction of left ventricular
      systolic pressure (LVSP), cardiomyocyte apoptosis and oxidative stress,
      manifesting as an increase in malondialdehyde (MDA) production and a decrease in
      superoxide dismutase (SOD) activity. Pretreatment of the hearts with 1.0 nmol/?l
      Ang-(1-7) for 30 min prior to ischemia considerably attenuated I/?R-induced VA,
      apoptosis and MDA production, and enhanced LVSP and SOD activity. These
      cardioprotective effects of Ang-(1-7) were antagonized by the intraperitoneal
      injection of 5 mg/?kg body weight indomethacin (IDM, a COX inhibitor), presenting
      as an enhancement of VA, apoptosis and MDA production as well as a reduction of
      LVSP and SOD activity. In conclusion, COX mediated Ang-(1-7)-induced
      cardioprotection via its antioxidative mechanism.

PMID- 21874246
TI  - Down-regulation of ghrelin receptors in the small intestine delays small
      intestinal transit in vagotomized rats.
AB  - Vagal nerve injury may occur in esophageal and gastric surgeries. The aim of this
      study was to observe the effects of ghrelin on small intestinal motility upon
      vagal nerve injury and the possible co-relationship between changes in ghrelin
      receptor expression in the small intestine and delayed small intestinal transit
      after vagotomy. The effects of intraperitoneal administration of ghrelin (20, 40
      and 80 ug/kg) and the ghrelin receptor antagonist [D-Lys3]-GHRP-6 (1.5 umol/kg)
      on small intestinal transit were studied in control and vagotomized rats in vivo.
      The effects of ghrelin (0.01, 0.1, 0.5, 1.0 and 2.0 umol/l) on the contraction
      force of smooth muscle strips from the jejunum were studied in the presence or
      absence of carbachol (50 nmol/l) and [D-Lys3]-GHRP-6 (10 umol/l) in vitro.
      Ghrelin receptor expression was assessed in intestinal muscle layers by means of
      Western blotting. The results indicated that ghrelin dose-dependently increased
      small intestinal transit in the control and model rats. In addition, ghrelin
      enhanced smooth muscle strip contraction induced by carbachol. Ghrelin receptor
      antagonist [D-Lys3]-GHRP-6 blocked the effect of ghrelin. Ghrelin receptor
      expression in the small intestinal muscle layers was down-regulated in the
      vagotomized rats. Down-regulation of growth hormone secretagogue receptor 1a in
      small intestinal muscle layers, which affected the function of ghrelin, may be
      one of the mechanisms behind delayed small intestinal transit after vagotomy.

PMID- 21874247
TI  - Highly expressed SLC35F2 in non-small cell lung cancer is associated with
      pathological staging.
AB  - Homo sapiens solute carrier family 35 member F2 (SLC35F2) is highly homologous to
      the lung squamous cell cancer-related gene, LSCC3, which is highly expressed in
      lung squamous cell tumour tissues. However, the clinical implication of the
      SLC35F2 gene in tumour development and progression remains unclear. An affinity
      purified polyclonal antibody raised against the human SLC35F2 peptide was used in
      the immunohistochemical analysis of a non-small cell lung cancer (NSCLC) tissue
      microarray of human NSCLC (n=129). SLC35F2 protein was also analysed with the
      same antibody using Western blotting. Total RNAs were extracted from tumour
      tissues (n=43) and from laser-dissected tumour cells (n=9). SLC35F2 gene
      expression was detected by fluorescent real-time quantitative PCR and compared to
      the expression in the corresponding adjacent normal lung tissues. It was found
      that both the SLC35F2 protein (by IHC analysis) and the SLS35F2 gene transcripts
      (by Q-PCR analysis) were expressed at significantly higher levels in the NSCLC
      tumour tissues than in the corresponding adjacent normal lung tissues (p<0.001
      and =0.015, respectively). There was a significant correlation between the
      SLC35F2 transcript and pathological staging (r=0.219, p=0.029), although the
      correlation between SLC35F2 protein and the staging was not significant
      (r=0.175). SLC35F2 was highly expressed in NSCLC tissues and the levels of
      expression, in particular the levels of the SLC35F2 transcript, were associated
      with NSCLC pathological staging. SLC35F2 appears to have a significant prognostic
      value in NSCLC.

PMID- 21874248
TI  - Molecular characteristics of pediatric non-ependymal, non-pilocytic gliomas
      associated with resistance to temozolomide.
AB  - Temozolomide constitutes current standard of care for adult patients with high
      grade gliomas. However, results for pediatric gliomas are rather disappointing.
      In order to investigate the molecular differences between pediatric and adult
      gliomas that could affect sensitivity to temozolomide, we studied 23 pediatric
      non-ependymal, non-pilocytic gliomas in comparison to 59 consecutive adult
      gliomas for the expression of O6-methylguanine methyltransferase (MGMT) and the
      DNA mismatch repair protein, mutS homolog 6 (MSH6) by immunohistochemistry, as
      well as for the presence or absence of promoter methylation of the MGMT gene by
      methylation-specific PCR. The expression of MGMT in pediatric gliomas was
      significantly higher than in adult gliomas, as shown by immunohistochemistry
      (p=0.00004). This association was conserved if statistical analysis was carried
      out only in astrocytic tumors (diffuse astrocytoma, anaplastic astrocytoma and
      glioblastoma, p=0.00007), or in oligodendroglial tumors (oligodendroglioma and
      anaplastic oligodendroglioma, p=0.020). Although methylation-specific PCR was
      successfully performed only in 15 pediatric gliomas, it also showed a trend
      toward less frequent methylation in pediatric as opposed to adult gliomas
      (p=0.242). MSH6 was almost equally expressed in pediatric and adult gliomas.
      Pediatric gliomas appear to have a distinct molecular profile associated with
      resistance to temozolomide. Higher expression of MGMT and a trend toward less
      frequent methylation of the promoter region of MGMT gene may partly account for
      relative resistance to temozolomide in pediatric gliomas as compared to adult
      gliomas.

PMID- 21874249
TI  - Anti-proliferative effect of an extract of the root of Polygonum multiflorum
      Thunb. on MCF-7 human breast cancer cells and the possible mechanisms.
AB  - The root of Polygonum multiflorum Thunb. (PM) is utilized to treat many diseases
      associated with aging. Research also indicates that PM inhibits the proliferation
      of certain types of cancer cells. The aim of the present study was to evaluate
      the inhibitory effect of PM extract (PME) on the proliferation of MCF-7 cells and
      to investigate the underlying mechanisms. Inhibition of the proliferation of MCF
      7 cells was determined by the MTT assay. Cell cycle distribution and apoptotic
      rates were evaluated by flow cytometry, and cell cycle and apoptosis-related
      protein expression was assessed by Western blotting. Apoptotic characteristics of
      MCF-7 cells were detected by transmission electron microscopy. The present study
      showed that PME at doses of 100, 150, 200 and 250 ug/ml significantly inhibited
      proliferation of MCF-7 cells in a time- and dose-dependent manner. Flow cytometry
      showed that the cell apoptotic rates were 9.1 +/- 1.67 and 17.7 +/- 2.93% after
      treatment with 100 and 200 ug/ml PME for 48 h, respectively. The proportions of
      cells in the G2/M phase were 37.9 +/- 1.47 and 42.0 +/- 1.71% after treatment
      with 100 and 200 ug/ml PME for 24 h, respectively. Western blot analysis showed
      that PME down-regulated the protein expression of Cdc25B and Cdc25C phosphatases
      accompanied by an increase in phospho-Cdk1, and PME promoted cytochrome c release
      from mitochondria into the cytosol to activate caspase-9. The present study
      demonstrated that PME inhibited MCF-7 cell proliferation by inducing cell cycle
      arrest in the G2/M phase and promoting cell apoptosis. The effects of PME on MCF
      7 cells were associated with the modulation of the expression levels of proteins
      involved in the cell cycle and apoptosis. These data suggest that PME has promise
      as a treatment against breast cancer by inhibiting the proliferation of cancer
      cells.

PMID- 21874250
TI  - Macrolides for the treatment of chronic bacterial prostatitis: an effective
      application of their unique pharmacokinetic and pharmacodynamic profile (Review).
AB  - Chronic bacterial prostatitis (CBP) is a persistent infection of the prostate
      characterized by poor quality of life mainly due to frequent relapse episodes
      caused by incomplete eradication of causative pathogens. Aggressive antibacterial
      therapy is required to attenuate the severe symptoms of CBP and to achieve a
      permanent cure. Although fluoroquinolones are currently recommended as first
      choice agents, macrolide antibiotics are emerging as a noteworthy option for the
      treatment of CBP. Macrolide antibiotics are characterized by an impressive array
      of distinct pharmacokinetic (PK) and pharmacodynamic (PD) properties. These
      properties include high intracellular accumulation in phagocytes and at sites of
      infection, including the prostate; broad antibiotic but also biofilm-inhibiting
      properties; immunomodulating and inflammation-resolving activities. These
      features offer particular advantages for the treatment of chronic infections of
      the prostate gland, which are not easily amenable to drug therapy. Macrolides may
      be exploited to counteract the unsatisfactory rates of clinical symptom
      improvement and pathogen eradication. The results of a number of clinical trials
      support this proposal.

PMID- 21874251
TI  - Development of quantitative DNA cleavage assay for XPG endonuclease activity
      using endogenous nuclear proteins in human cell lines.
AB  - XPG, a structure-specific DNA endonuclease responsible for the 3' incision of DNA
      lesions during nucleotide excision repair (NER), is associated with high risk of
      skin cancer as well as skeletal, neurological and developmental abnormalities
      when functionally defective. These observations have led to the model wherein the
      endonuclease activity of XPG is important for NER. Herein, we first demonstrate a
      sensitive assay of XPG cleavage activity using direct nuclear extracts as an XPG
      source. This method provided quantitative evaluation of the activity of
      endogenous XPG endonuclease derived from cells with high reproducibility. Our new
      assay takes advantage of 3'-end oligolabeling of the bubble-shaped substrate. Our
      results demonstrate efficient cleavage of the model substrate in two XPG wild
      type cell lines (human fibroblasts and RKO colon cancer cells) in a time- and
      dose-dependent manner. In addition, XPG-deficient cells manifested lower cleavage
      activity relative to normal XPG cells, indicating that the incision activity of
      XPG was intrinsic in our methodology. It was also found that 7 mM MgCl2 and
      buffer pH 6.8 resulted in optimal endonucleolytic activity. Based on these
      results, our modified methodology has potential for quantitative monitoring of
      XPG cleavage activity in any cell type or tissue of interest.

PMID- 21874252
TI  - Highly sensitive lens culinaris agglutinin-reactive alpha-fetoprotein is useful
      for early detection of hepatocellular carcinoma in patients with chronic liver
      disease.
AB  - The fucosylated fraction of alpha-fetoprotein (AFP-L3) is a specific marker for
      hepatocellular carcinoma (HCC). However, conventional AFP-L3% (c-AFP-L3%) has not
      always been reliable in cases with low serum alpha-fetoprotein (AFP) levels. In
      this study, we evaluated the clinical utility of a newly developed assay, highly
      sensitive AFP-L3% (hs-AFP-L3%). Subjects included 74 patients with benign liver
      disease (BLD), including chronic hepatitis and cirrhosis, and 94 with HCC. Serum
      hs-AFP-L3% was significantly higher than c-AFP-L3% in patients with early-stage
      HCC (solitary or <20 mm in diameter). Additionally, hs-AFP-L3% was significantly
      increased in patients with well-differentiated HCC. In patients with serum AFP
      <20 ng/ml, the sensitivities of c-AFP-L3% and hs-AFP-L3% were 12.5 and 44.6%,
      respectively, at a cut-off value of 5%. In 59 BLD patients with serum AFP <20
      ng/ml, the HCC-positive rate in patients with hs-AFP-L3% >= 5% was significantly
      higher compared to those with hs-AFP-L3% <5% during the follow-up period (median,
      35 months; range, 5-48 months). Importantly, none of the BLD patients with both
      serum AFP <20 ng/ml and hs-AFP-L3% <5% developed HCC. These results indicated
      that hs-AFP-L3% is useful for early detection of HCC in BLD patients, even for
      those with serum AFP <20 ng/ml. Furthermore, since hs-AFP-L3% increases before
      HCC is detectable by various advanced imaging modalities, this assay may help
      identify BLD patients with a higher risk of HCC.

PMID- 21874254
TI  - MHC class II genotype- and MHC class I and II phenotype-related parameters in
      sporadic colorectal cancer.
AB  - The underlying etiological cause of non-hereditary colorectal cancer has yet to
      be determined. The adenoma-carcinoma sequence is widely accepted, however, a sole
      trigger has not been specified. Therefore, we sought to further define genotypic
      and phenotypic parameters that could be involved in promoting a possible
      infection, inflammation and hyper-proliferation, followed by the adenoma
      carcinoma sequence. Expression of phenotype-related parameters for MHC class I
      (HLA-A N-20 and beta2 microglobulin) and class II (HLA-DRalpha and HLA-DR) as
      well as CD45 and carcinoembryonic antigen (CEA) were investigated
      immunohistochemically in a series of 93 colorectal cancers. Additionally, in 49
      of the tumours the MHC class II genotype was analysed. MHC class II genotype
      analyses revealed a tendency towards DRB1*08 and DQB1*04. A significant
      association among the MHC class I markers or the MHC class II markers was found.
      No difference in marker expression could be detected between tumour and stromal
      tissue, however a significant inverse expression existed for markers of the
      functionally different class I or II systems. With the exception of CEA, there
      was no correlation between expression of any marker and tumour grade. Only 2% of
      tumours expressed no markers for MHC class I and II. Further studies on MHC class
      I and II genotype and phenotype relation in colorectal cancer may help to
      identify trigger mechanisms for tumourigenesis, involved markers and possible
      mechanisms of subsequent immune escape.

PMID- 21874253
TI  - Lipopolysaccharide initiates a bypass feedback loop of epidermal growth factor
      receptor signaling by HPS70-induced COX-2 in H22 hepatocarcinoma cells.
AB  - LPS can induce TACE upregulation via signaling from TLR4-derived EGFR activation
      in tumor cells. The regulation and activity of TACE have been investigated with
      the observation that gene expression is upregulated in response to LPS followed
      by EGFR activation, however, the process remains poorly understood. In this
      study, we examined the effects of LPS on H22 hepatocarcinoma cells that displayed
      constitutively active TLR4 expression. Upon TLR4 shRNA transfection into H22
      cells, HSP70 expression significantly increased. However, LPS induced early
      phosphorylation of EGFR in H22 cells, which reached maximum levels within 30 min.
      Inhibition of TLR4 in H22 cells resulted in a significant rise in both EGFR
      phosphorylation and TACE upregulation 24 h after exposure to LPS. Exogenous HSP70
      also induced rapid phosphorylation of EGFR, upregulated the expression of COX-2
      via a signaling pathway that involved TACE-dependent TGF-alpha release.
      Furthermore, inhibition of EGFR activation and reduction of COX-2 expression by
      COX-2 inhibitor prevented HSP70-induced cell invasion in vitro. These findings
      demonstrate that the biological importance of HSP70/COX-2 is crucial to the
      second, but not the first, phase of EGFR phosphorylation in tumor cells. The
      growth of tumor cells by inserting shRNA plasmid TLR4 combination with COX-2
      inhibitor could be effectively reduced in LPS stimulation. We concluded that LPS
      triggered a bypass feedback loop of EGFR activation and involved HSP70/COX-2 in
      H22 cells by inhibition of TLR4 and that EGFR phosphorylation is implicated in
      tumor growth by LPS stimulation.

PMID- 21874255
TI  - IDH mutations occur frequently in Chinese glioma patients and predict longer
      survival but not response to concomitant chemoradiotherapy in anaplastic gliomas.
AB  - Mutations in the isocitrate dehydrogenase 1 and 2 genes (IDH1 and IDH2) appear to
      occur frequently and selectively in gliomas. Our aim was to assess whether IDH
      mutations are common in Chinese glioma patients and whether the mutations predict
      good response to concomitant chemoradiotherapy. In this study IDH1 and IDH2
      mutations were detected in a series of 203 gliomas. IDH1 mutations were present
      in 75 of the 203 cases (36.9%) while IDH2 mutations in 5 of the 203 cases (2.5%).
      No tumor was mutated in both IDH1 and IDH2. IDH1/2 mutations were associated with
      prolonged overall survival in the whole series of patients exclusive of pilocytic
      astrocytoma (P<0.001), WHO grade II patients who received no adjuvant therapy
      after surgery (P=0.014) and WHO grade III patients who received concomitant
      chemoradiotherapy (standard schedule) after surgery (P=0.033). Furthermore, there
      was no correlation between IDH1/2 mutations and reponse to concomitant
      chemoradiotherapy in anaplastic gliomas. Our results suggest that IDH1 mutations
      also occur freuqently in Chinese glioma patients but the frequency of IDH1
      mutations is below the findings reported by North American and European groups.
      Furthermore, we confirm the prognostic significance of IDH1/2 mutations in
      gliomas, but the mutations cannot predict a favorable response to concomitant
      chemoradiotherapy in anaplastic gliomas.

PMID- 21874256
TI  - Up-regulation of neutrophil gelatinase-associated lipocalin in oral squamous cell
      carcinoma: relation to cell differentiation.
AB  - Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin2, LCN2)
      is a secreted glycoprotein with increased expression in solid tumors. The
      expression and functions of NGAL in oral cancer, however, remain unclear. We
      investigated the expression of NGAL in oral cancer tissues and oral cancer cell
      lines. By immunohistochemical examinations, NGAL expression was strongly up
      regulated in well-differentiated OSCC tissues and moderately to weakly up
      regulated in moderately to poorly differentiated OSCC tissues. In contrast, NGAL
      expression was weak or very weak in normal mucosa and leukoplakia. By western
      blot analysis, NGAL expression levels positively correlated with cell morphology
      patterns and loss of E-cadherin. In addition, the enzymatic activity of the
      NGAL/MMP-9 complex significantly correlated with the results obtained by
      zymographic analysis. In conclusion, NGAL expression is high in well
      differentiated cancer, suggesting that NGAL may be a useful diagnostic marker of
      tumor-cell differentiation.

PMID- 21874257
TI  - Re-expression of estrogen receptor beta inhibits the proliferation and migration
      of ovarian clear cell adenocarcinoma cells.
AB  - Ovarian clear cell adenocarcinoma (OCCA) is an aggressive ovarian malignancy with
      a poor prognosis. The role of estrogen receptor beta (ERbeta) in the development
      of OCCA remains to be clarified. To investigate the action of ERbeta in the
      proliferation and invasion of OCCA cells, the ES-2 cell line was stably
      transfected with full-length human ERbeta cDNA, and clones were screened and
      identified using RT-PCR and western blot assay. ERbeta stable transfectants,
      referred to as ESbeta1 and ESbeta2 cells, were compared with mock transfectant
      ESVE and parental ES-2 cells with respect to their growth, motility and ability
      to activate target genes. ESbeta1 and ESbeta2 cells expressed ERbeta mRNA and
      protein, whereas ES-2 and ESVE cells were ERbeta negative. ERbeta transfectants
      exhibited distinct characteristics from ES-2 and ESVE cells including
      proliferative properties and the ability to express cyclin D1 in the presence of
      17beta-estradiol (E2). ERbeta inhibited ES-2 cell proliferation, which was
      determined using the MTT assay, BrdU labeling method and by the down-regulation
      of cyclin D1 gene expression. Moreover, exogenous ERbeta expression resulted in a
      significant inhibition of ES-2 cell motility in an in vitro invasion assay.
      ERbeta reduced the expression of MMP2 mRNA and the activity of MMP2 enzymatic
      activity in a ligand-dependent manner. In summary, ERbeta may inhibit the
      proliferation and invasion of ES-2 cells and may be an important regulator in
      OCCA carcinogenesis.

PMID- 21874258
TI  - Cyclooxygenase-2 expression is not associated with clinical outcome in synovial
      sarcoma.
AB  - Several studies have identified cyclooxygenase-2 (COX-2) expression in a variety
      of sarcomas, including rhabdomyosarcoma, osteosarcoma and chondrosarcoma.
      Although overexpression of COX-2 has been associated with poor prognosis and
      decreased survival in chondrosarcoma and osteosarcoma, no relationship between
      COX-2 expression and patient outcome has been demonstrated in rhabdomyosarcoma or
      adult soft tissue sarcomas. Little is known concerning the expression of COX-2 in
      synovial sarcoma. Therefore, the aim of this study was to examine the expression
      of COX-2 in synovial sarcoma and if shown, to identify any association with tumor
      stage and oncologic outcome. Paraffin-embedded specimens from 27 patients with
      synovial sarcoma who were treated with surgical resection or biopsy were
      obtained. Specimens were evaluated for the degree of COX-2 expression after
      immunohistochemical staining. Specimens were assigned an immunoreactivity score
      (IS) based on the percent positivity of the specimen. A retrospective chart
      analysis was performed to determine the clinical stage at presentation, incidence
      of local recurrence, presence of metastatic disease and overall survival.
      Statistical analysis was then performed to determine whether there was a
      significant relationship between IS and stage at presentation or patient
      outcomes. COX-2 expression was detected in 18 of 27 (66.67%) of the pathological
      specimens. There was a statistically significant relationship between COX-2
      expression and patient clinical stage at presentation; however, we were unable to
      identify a significant relationship between IS and patient survival. We also
      found no significant relationship between IS and development of metastases or
      local recurrence. COX-2 was expressed to some degree in 67% of the tumor
      specimens. There was a significant relationship between IS and patient stage at
      presentation, but no significant relationship between COX-2 expression and
      clinical outcome could be identified. The fact that these tumors do express COX
      2, however, suggests the potential for an additional target for more effective
      therapy.

PMID- 21874259
TI  - Phosphorylation and stabilization of c-Myc by NEMO renders cells resistant to
      ionizing radiation through up-regulation of gamma-GCS.
AB  - The transcription factor c-Myc has been previously shown to be phosphorylated and
      stabilized by NEMO through direct interaction in the nucleus. Here, we show that
      NEMO induces up-regulation of the c-Myc target protein, gamma-glutamyl-cysteine
      synthetase (gamma-GCS), leading to an increase of intracellular glutathione (GSH)
      levels and simultaneous enhancement of redox-controlling capacity. NEMO enhanced
      c-Myc recruitment to gamma-GCS promoters and c-Myc was essential for NEMO
      mediated gamma-GCS up-regulation. The phosphorylation and stabilization of c-Myc
      by NEMO rendered cells more resistant to ionizing radiation (IR). Thus, the
      interaction between NEMO and c-Myc may be targeted for the development of
      strategies to overcome the resistance to radiotherapy.

PMID- 21874260
TI  - Combination of branched-chain amino acids and angiotensin-converting enzyme
      inhibitor suppresses the cumulative recurrence of hepatocellular carcinoma: a
      randomized control trial.
AB  - Insulin resistance (IR) is reportedly involved in the progression of
      hepatocellular carcinoma (HCC). Since neovascularization plays an important role
      in hepatocarcinogenesis and IR, an angiostatic therapy may be considered as one
      of the promising approaches for chemoprevention against HCC. The aim of the
      current study was to examine the combination effect of a clinically used branched
      chain amino acid (BCAA) and an angiotensin-converting enzyme inhibitor (ACE-I),
      both reportedly possess anti-angiogenic and IR-improving activities, on the
      cumulative recurrence after curative therapy. BCAA granules (Livact; 12 g/day)
      and/or ACE-I (perindopril; 4 mg/day) were administered after the curative therapy
      for HCC, and several indices were analyzed. A 48-month follow-up revealed that
      the combination treatment with BCAA and ACE-I markedly inhibited the cumulative
      recurrence of HCC under IR conditions, whereas neither single treatment exerted a
      significant inhibition. The soluble form of the vascular endothelial growth
      factor (VEGF; a central angiogenic factor) receptor-2 (sVEGFR2) was significantly
      decreased only three months after the treatment without recurrence. We also
      observed that IR, determined by the homeostasis model assessment (HOMA-IR), was
      significantly improved by this regimen, indicating that an inhibitory effect was
      achieved, at least partly, by coordinated effects of anti-angiogenesis and IR
      improvement. In conclusion, since both BCAA and ACE-I are widely used in clinical
      practice with safety, this combination therapy may represent a potential new
      strategy for chemoprevention against IR-based HCC recurrence in the future.
      Moreover, sVEGFR2 may become a useful clinical predictive marker of this
      combination treatment.

PMID- 21874261
TI  - Down-regulation of urokinase plasminogen activator and matrix metalloproteinases
      and up-regulation of their inhibitors by a novel nutrient mixture in human
      prostate cancer cell lines PC-3 and DU-145.
AB  - Strong clinical and experimental evidence shows that elevated levels of urokinase
      plasminogen activators (u-PA) and matrix metalloproteinases (MMPs) are associated
      with prostate cancer progression, metastasis and shortened survival in patients.
      MMP activities are regulated by specific tissue inhibitors of metalloproteinases
      (TIMPs). A nutrient mixture (NM) containing lysine, proline, ascorbic acid and
      green tea extract showed anticancer activity against a number of cancer cell
      lines. Our main objective was to study the effect of NM on the activity of u-PA,
      MMPs and their inhibitor TIMPs on human prostate cancer cell lines PC-3 and DU
      145. Human prostate cancer cell lines PC-3 and DU-145 (ATCC) were grown in MEM
      media with 10% FBS and antibiotics in 24-well tissue culture plates. At near
      confluence, the cells were treated with NM at 0-1000 ug/ml in triplicate at each
      concentration. Analysis of u-PA activity was carried out by fibrin zymography,
      MMPs by gelatinase zymography and TIMPs by reverse zymography. Both PC-3 and DU
      145 prostate cancer cell lines demonstrated u-PA activity (subunits 1 and 2,
      corresponding to 35 and 33 kDa). Prostate cancer cell line PC-3 secretion of u-PA
      subunit 1 was decreased by 65% at NM 500 ug/ml and subunit 2 by 100% at NM 50
      ug/ml. Prostate cancer cell line DU-145 secretion of u-PA subunit 1 was decreased
      by 97% at NM 500 ug/ml and subunit 2 by 100% at NM 100 ug/ml. Untreated PC-3
      showed two bands for MMP-2 and MMP-9. NM inhibited their expression in a dose
      dependent manner. The activity of MMP-2 and MMP-9 was significantly inhibited at
      250 ug/ml with total inhibition at 500 ug/ml. DU-145 cells did not exhibit MMP
      activity. Activity of TIMPs was up-regulated in both prostate cancer cell lines
      in a dose-dependent manner. Minimum activity was expressed at 50 ug/ml NM and
      maximum at 1000 ug/ml. Correlation analyses revealed a positive correlation
      between u-PA and MMPs and a negative correlation between u-PA/MMPs and TIMPs.
      These results suggest NM as a potential anticancer agent since it targets
      invasive parameters of prostate cancer.

PMID- 21874262
TI  - Small interfering RNA-directed targeting of RON alters invasive and oncogenic
      phenotypes of human hepatocellular carcinoma cells.
AB  - The recepteur d'origine nantais (RON) receptor tyrosine kinase is highly
      expressed in various cancers including human hepatocellular carcinoma (HCC) and
      involved in tumor progression. The aims of the current study were to evaluate
      whether RON affects tumor cell behavior and oncogenic signaling cascades in HCC
      cells. We investigated the biologic role of RON on tumor cell behavior and
      oncogenic signaling cascades including Akt, c-Raf and extracellular signal
      regulated kinase (ERK) by using the small interfering RNA (siRNA) in HCC cell
      lines, chang, HepG2 and Huh7. Knockdown of RON suppressed tumor cell migration
      and invasion in all tested HCC cell lines. The proportion of apoptotic cells
      induced by knockdown of RON was greater than that induced by transfection of the
      scramble siRNA in all tested HCC cell lines. Knockdown of RON resulted in cell
      cycle arrest in the G2/M phase of chang and Huh7 cells, and sub G1 phase of HepG2
      cells. Knockdown of RON activated cleaved caspase-3 and PARP, and down-regulated
      the expression of Bcl-2, Bcl-xL and survivin, leading to induction of apoptosis
      in all tested cell lines. Knockdown of RON negatively regulates the progression
      of the cell cycle by decreasing cyclin D1 and D3, and increasing p21 and p27 in
      all tested cell lines. The phosphorylation of Akt, c-Raf and ERK1/2 signal
      proteins was significantly blocked by knockdown of RON in all tested cell lines.
      These results suggest that RON is associated with invasive and oncogenic
      phenotypes such as tumor cell migration, invasion, resistance to apoptosis and
      cell cycle arrest through the modulation of Akt, c-Raf and ERK signaling cascades
      in HCC cells.

PMID- 21874263
TI  - 4-hexylresorcinol inhibits NF-kappaB phosphorylation and has a synergistic effect
      with cisplatin in KB cells.
AB  - Cisplatin is a representative anti-cancer drug and 4-hexylresorcinol (4-HR) is
      known as an antiparasitic and antiseptic agent. The aims of this study were to
      evaluate the effect of 4-HR on the activation of nuclear factor-kappaB (NF
      kappaB) in cell cultures, to evaluate the antitumor effect of 4-HR plus cisplatin
      combination therapy in a xenograft model, and to evaluate transglutaminase-2 (TG
      2) and phosphorylated NF-kappaB (pNF-kappaB) expression in the xenograft model.
      To determine the effect of 4-HR on NF-kappaB phosphorylation, co
      immunoprecipitation and Western blot analysis were done in KB cells. To examine
      the in vivo effect of the cisplatin plus 4-HR combination therapy, KB cells were
      grafted into nude mice. Drugs were injected into the peritoneal cavity daily.
      Tumor size, body weight, and duration of survival were checked daily. Specimens
      from main mass were used in immunohistochemical staining for the analysis of TG-2
      and pNF-kappaB expression. In the in vitro test, as the 4-HR concentrations
      increased, the fraction of the bound complex NF-kappaB-inhibitory-kappaB
      (IkappaB) increased. Consequently, the level of free IkappaB decreased. In the
      xenograft model, the cisplatin plus 4-HR group exhibited a significantly
      decreased tumor growth rate than in the saline group (P=0.039). The mean survival
      time of the cisplatin plus 4-HR group was 51.20+/-3.96 days and was significantly
      prolonged compared with the other groups (P<0.05). The body weight of the
      cisplatin plus 4-HR group had significantly less weight loss than the cisplatin
      only group (P=0.045). In the immunohistochemical analysis, the cisplatin plus 4
      HR group had a significantly lower expression of TG-2 and pNF-kappaB compared to
      the saline group (P<0.05). In conclusion, cisplatin plus 4-HR combination therapy
      had clear advantages over the cisplatin only treatment such as similar tumor
      growth inhibition compared to the cisplatin only treatment despite the reduced
      dosage of cisplatin, less body weight loss, and prolonged survival time.

PMID- 21874264
TI  - Identification of new aberrantly expressed miRNAs in intestinal-type gastric
      cancer and its clinical significance.
AB  - miRNAs are small 19 to 22 nucleotide sequences of RNA that negatively regulate
      gene expression. miRNA expression profiles may become useful biomarkers for
      diagnostics, prognosis and prediction of response to treat, and it could be a
      powerful tool for cancer prevention and therapeutics. Several miRNA expression
      profiles of miRNAs in gastric cancer have been reported, but these studies
      screened only few miRNAs and samples used in experiments include several
      different subtypes of gastric cancers, which decrease the sensitivity to identify
      new aberrant miRNAs. In this study, a miRNA expression profile was identified by
      miRCURY LNA Array (v.14.0) between intestinal-type gastric cancers and normal
      tissues. Forty miRNA precursors were up-regulated and thirty-six miRNA were down
      regulated in intestinal-type gastric cancers (p<0.01). Sixteen new miRNAs were
      found in intestinal-type gastric cancers. Seventeen new miRNAs were found in
      intestinal-type gastric cancers. miR-145, miR-27a, miR-494 are differently
      expressed between intestinal-type and diffuse-type gastric cancers. miR-32, miR
      182 and miR-143 dysregulated expression levels are related with different
      pathological stages of intestinal-type gastric cancers (p<0.01). Taken together,
      aberrantly expressed miRNAs may offer new clues to tumorigenesis of gastric
      cancers. miR-32, miR-182 and miR-143 may be potential diagnostic biomarkers for
      intestinal-type gastric cancers.

PMID- 21874265
TI  - Vasodilator-stimulated phosphoprotein regulates osteosarcoma cell migration.
AB  - Vasodilator-stimulated phosphoprotein (VASP) has been reported to play an
      important role in the process of cell migration and tumor metastasis. However, to
      date, no study has examined VASP expression and its function in osteocarcoma
      cells. In this study, we analyzed the effect of VASP on osteosarcoma cell
      migration and the signal transduction pathways involved. We used two osteosarcoma
      cell strains (Mg-63 and Saos-2 cells) with different metastatic potential.
      Silencing of VASP gene expression was carried out using RNA interference in these
      cells. Knockdown of expression at the transcriptional or translational level was
      determined by RT-PCR or western blot analysis, respectively. The metastatic
      potential of the tumor cells was determined by a wound healing migration assay.
      VASP mRNA expression was also determined in 30 human osteosarcoma samples.
      Furthermore, Rac1 was determined as a regulator of VASP function. RT-PCR and
      western blotting showed that Mg-63 cells had a significantly higher VASP
      expression at both the transcriptional and translational levels compared to Saos
      2 cells. The wound healing assay revealed that Mg-63 cells had more migratory
      potential compared to Saos-2 cells. The effect was found to be reversible when
      VASP was knocked down by siRNA in Mg-63 cells. Specimens from human patients with
      metastases had higher VASP expression compared to specimens of patients without
      metastases. Knockdown of Rac1 resulted in inhibition of VASP expression in
      sarcoma cells. These results suggest that VASP protein regulates osteosarcoma
      cell migration and metastasis. Rac1 and VASP interaction may be a potential
      target for osteo-sarcoma treatment.

PMID- 21874266
TI  - Hydrogen peroxide controls Akt activity via ubiquitination/degradation pathways.
AB  - Akt is a well-established protein that regulates cell growth, survival and anti
      apoptotic mechanisms. In this study, we demonstrated that hydrogen peroxide
      (H2O2)-induced oxidative stress regulates the activity of the anti-apoptotic
      protein Akt via the ubiquitin-proteasome degradation system. H2O2 induced
      cytotoxicity in PC12 cells and decreased the cellular protein and phosphorylation
      levels of Akt in a concentration- and exposure time-dependent manner. This
      downregulation was blocked by the proteasome inhibitor MG132 and the Akt-specific
      inhibitor LY294002. In addition, an in vivo ubiquitination assay revealed that
      the degradation of Akt was mediated by the ubiquitin-mediated proteasome pathway
      and further demonstrated that this ubiquitination was dependent on the
      phosphorylation status of Akt. Furthermore, the exogenously overexpressed active
      form of Akt, but not its inactive form, induced resistance to H2O2-mediated cell
      death. These results suggested that H2O2-induced cytotoxicity was mediated by
      active Akt degradation.

PMID- 21874268
TI  - His6-OPH enzyme-based bio-hybrid material for organophosphate detection.
AB  - In this work, we report on the development of a bio-sensing film for the
      detection of organophosphorous compounds using sol-gel technology. A novel sol
      gel immobilization method employing tetraethoxysilane/3
      glycidoxypropyltrimethoxysilane/water hybrid material was developed and used to
      immobilize the hexahistidine-tagged organophosphorous hydrolase enzyme (His(6)
      OPH). Bio-sensing layers with encapsulated His(6)-OPH of various structures
      (water/silane, precursor ratios) have been prepared. The optimal (P = 5:1, R =
      188) bio-sensing layers retained 90% of the initial enzyme activity. Furthermore,
      the bio-sensing layer prepared by this method was able to maintain its activity
      at or above 80% of its initial activity for 2 weeks. The bio-hybrid film also
      showed excellent reusability and improved activity at neutral pH in comparison to
      the same enzyme in solution.

PMID- 21874269
TI  - Determination of dextromethorphan in human plasma using pipette tip solid-phase
      extraction and gas chromatography-mass spectrometry.
AB  - Dextromethorphan was extracted from human plasma samples (100 MUL) using MonoTip
      C(18) tips, which are packed with C(18)-bonded monolithic silica gel that is
      attached to the inside of the tip. The samples, which contained dextromethorphan
      and trimeprazine as an internal standard (IS), were mixed with 200 MUL of
      distilled water and 50 MUL of 1 mol/L glycine-sodium hydroxide buffer (pH 10).
      The mixture was extracted to the C(18) phase of the tip by 20 sequential
      aspirating/dispensing cycles using a manual micropipettor. The analytes retained
      on the C(18) phase were then eluted with methanol by five sequential
      aspirating/dispensing cycles. The eluate was injected directly into a gas
      chromatograph and detected by a mass spectrometer with selected ion monitoring in
      positive electron ionization mode. An Equity-5 fused silica capillary column (30
      m * 0.32 mm i.d., film thickness 0.5 MUm) gave adequate separation of the
      dextromethorphan, IS, and impurities. The recoveries of dextromethorphan and the
      IS spiked into plasma were >87.4%. The regression equation for dextromethorphan
      showed excellent linearity from 2.5 to 320 ng/mL of plasma, and the limit of
      detection was 1.25 ng/mL of plasma. The intraday and interday coefficients of
      variation were less than 10.5% and 14.7%, respectively. The accuracy ranged from
      91.9% to 107%. The validated method was successfully used to quantify the plasma
      concentration of dextromethorphan in a human subject after oral administration of
      the drug.

PMID- 21874270
TI  - Determination of ultra-trace levels of priority PBDEs in water samples by isotope
      dilution GC(ECNI)MS using 81Br-labelled standards.
AB  - A gas chromatography electron capture negative ionization mass spectrometry
      (GC(ECNI)MS) procedure for the determination of priority polybrominated diphenyl
      ethers (PBDEs; congeners 28, 47, 99, 100, 153 and 154) in water samples at
      regulatory EU levels has been developed. The method is based on the use of (81)Br
      labelled PBDEs for isotope dilution analysis and the measurement of (79)Br/(81)Br
      isotope ratios in gas chromatography peaks with the electron capture negative
      ionization technique. The suitability of this ion source for the precise and
      accurate measurement of bromine isotope ratios has been demonstrated. The general
      ECNI-IDMS procedure was evaluated by the analysis of NIST SRM 1947 (Lake Michigan
      fish tissue) with satisfactory results. For the analysis of water samples, 500 mL
      of the samples were spiked with the labelled PBDEs and extracted with 10 mL
      isooctane for 30 min. The extract was evaporated down to ca. 100 MUL and injected
      in the GC(ECNI)MS. Detection limits ranged from 0.014 (-1) to 0.089 pg mL(-1)
      depending on the congener. Recoveries from real water samples, spiked at a level
      of 0.5 pg mL(-1), ranged from 77% to 102%.

PMID- 21874271
TI  - Hardware-related infections after deep brain stimulation surgery: review of
      incidence, severity and management in 212 single-center procedures in the first
      year after implantation.
AB  - BACKGROUND: Device-related infection is a common occurrence after deep brain
      stimulation (DBS) surgery, and may result in additional interventions and a loss
      of efficacy of therapy. This retrospective review aimed to evaluate the
      incidence, severity and management of device-related infections in 212 DBS
      procedures performed in our institute. METHODS: Data on 106 patients, in whom 212
      DBS procedures were performed between 2001 and 2011 at our institute by a single
      neurosurgeon (M.P.), were reviewed to assess the incidence, severity, management
      and clinical characteristics of infections in the first year after the
      implantation of a DBS system. RESULTS: Infections occurred in 8.5% of patients
      and 4.2% of procedures. Of the nine infections, eight involved the
      neurostimulator and extensions, and one the whole system. The infections occurred
      30.7 days after implantation: 7 within 30 days and 2 within 6 months. Infected
      and uninfected patients were comparable in terms of age, sex, indication for DBS
      implantation and neurostimulator location. In eight cases, the system components
      involved were removed and re-implanted after 3 months, while in one case the
      complete hardware was removed and not re-implanted. CONCLUSION: The overall
      incidence of postoperative infections after DBS system implantation was 4.2%;
      this rate decreased over time. All infections required further surgery. Correct
      and timely management of partial infections may result in successful salvage of
      part of the system.

PMID- 21874272
TI  - Fish oil supplementation during late pregnancy does not influence plasma lipids
      or lipoprotein levels in young adult offspring.
AB  - Nutritional influences on cardiovascular disease operate throughout life. Studies
      in both experimental animals and humans have suggested that changes in the peri-
      and early post-natal nutrition can affect the development of the various
      components of the metabolic syndrome in adult life. This has lead to the
      hypothesis that n-3 fatty acid supplementation in pregnancy may have a beneficial
      effect on lipid profile in the offspring. The aim of the present study was to
      investigate the effect of supplementation with n-3 fatty acids during the third
      trimester of pregnancy on lipids and lipoproteins in the 19-year-old offspring.
      The study was based on the follow-up of a randomized controlled trial from 1990
      where 533 pregnant women were randomized to fish oil (n = 266), olive oil (n =
      136) or no oil (n = 131). In 2009, the offspring were invited to a physical
      examination including blood sampling. A total of 243 of the offspring
      participated. Lipid values did not differ between the fish oil and olive oil
      groups. The relative adjusted difference (95% confidence intervals) in lipid
      concentrations was -3% (-11; 7) for LDL cholesterol, 3% (-3; 10) for HDL
      cholesterol, -1% (-6; 5) for total cholesterol,-4% (-16; 10) for TAG
      concentrations, 2%(-2; 7) for apolipoprotein A1, -1% (-9; 7) for apolipoprotein B
      and 3% (-7; 15) in relative abundance of small dense LDL. In conclusion, there
      was no effect of fish oil supplementation during the third trimester of pregnancy
      on offspring plasma lipids and lipoproteins in adolescence.

PMID- 21874273
TI  - Role of a disordered steroid metabolome in the elucidation of sterol and steroid
      biosynthesis.
AB  - In 1937 Butler and Marrian found large amounts of the steroid pregnanetriol in
      urine from a patient with the adrenogenital syndrome, a virilizing condition
      known to be caused by compromised adrenal secretion even in this pre-cortisol
      era. This introduced the concept of the study of altered excretion of metabolites
      as an in vivo tool for understanding sterol and steroid biosynthesis. This
      approach is still viable and has experienced renewed significance as the field of
      metabolomics. From the first cyclized sterol lanosterol to the most downstream
      product estradiol, there are probably greater than 30 steps. Based on a
      distinctive metabolome clinical disorders have now been attributed to about seven
      post-squalene cholesterol (C) biosynthetic steps and around 15 en-route to
      steroid hormones or needed for further metabolism of such hormones. Forty years
      ago it was widely perceived that the principal steroid biosynthetic defects were
      known but interest rekindled as novel metabolomes were documented. In his career
      this investigator has been involved in the study of many steroid disorders, the
      two most recent being P450 oxidoreductase deficiency and apparent cortisone
      reductase deficiency. These are of interest as they are due not to mutations in
      the primary catalytic enzymes of steroidogenesis but in ancillary enzymes needed
      for co-factor oxido-reduction A third focus of this researcher is Smith-Lemli
      Opitz syndrome (SLOS), a cholesterol synthesis disorder caused by 7
      dehydrocholesterol reductase mutations. The late George Schroepfer, in whose
      honor this article has been written, contributed greatly to defining the sterol
      metabolome of this condition. Defining the cause of clinically severe disorders
      can lead to improved treatment options. We are now involved in murine gene
      therapy studies for SLOS which, if successful could in the future offer an
      alternative therapy for this severe condition.

PMID- 21874274
TI  - Recent advances on biological difructose anhydride III production using inulase
      II from inulin.
AB  - Difructose anhydride III (DFA III), the smallest cyclic disaccharide, consists of
      two fructose residues. DFA III is a hydrolysate of inulin and is rarely found in
      nature. Industrial interest in DFA III as a low-calorie sugar substitute is
      increasing. The present review describes the properties and physiological
      functions of DFA III as well as its commercial importance. Focus is also given on
      the biological production of DFA III from inulin, which contains enzyme
      resources, inulase II properties, and the capacity for mass DFA III production.
      Inulase II as an industrial enzyme and its molecular evolution are discussed as
      well. The aim is to better understand commercial-scale DFA III production as a
      food product.

PMID- 21874275
TI  - Perspectives of biotechnological production of L-ribose and its purification.
AB  - L-ribose is a non-natural and expensive sugar that can be used as an important
      intermediate for the synthesis of L-nucleoside analogues, which are used as
      antiviral drugs. In contrast to chemical production, biotechnological methods can
      produce L-ribose from biomass under environmentally friendly conditions. In this
      mini-review, various strategies for synthesizing L-ribose by applying
      microorganisms and their enzymes are discussed, including microbial
      biotransformation and biocatalysis by engineering bacteria. Furthermore,
      subsequent isolation-and-purification techniques, as an integral step in the
      whole process, are accordingly described, containing the special introduction of
      a promising strategy of L-ribose separation. Particularly, further researches and
      outlook for the improvement of L-ribose preparation was solely stressed. Compared
      with each method, this mini-review provides a panorama of respective advantages
      and disadvantages existing in them.

PMID- 21874277
TI  - Mutant selection and phenotypic and genetic characterization of ethanol-tolerant
      strains of Clostridium thermocellum.
AB  - Clostridium thermocellum is a model microorganism for converting cellulosic
      biomass into fuels and chemicals via consolidated bioprocessing. One of the
      challenges for industrial application of this organism is its low ethanol
      tolerance, typically 1-2% (w/v) in wild-type strains. In this study, we report
      the development and characterization of mutant C. thermocellum strains that can
      grow in the presence of high ethanol concentrations. Starting from a single
      colony, wild-type C. thermocellum ATCC 27405 was sub-cultured and adapted for
      growth in up to 50 g/L ethanol using either cellobiose or crystalline cellulose
      as the growth substrate. Both the adapted strains retained their ability to grow
      on either substrate and displayed a higher growth rate and biomass yield than the
      wild-type strain in the absence of ethanol. With added ethanol in the media, the
      mutant strains displayed an inverse correlation between ethanol concentration and
      growth rate or biomass yield. Genome sequencing revealed six common mutations in
      the two ethanol-tolerant strains including an alcohol dehydrogenase gene and
      genes involved in arginine/pyrimidine biosynthetic pathway. The potential role of
      these mutations in ethanol tolerance phenotype is discussed.

PMID- 21874276
TI  - A broader role for AmyR in Aspergillus niger: regulation of the utilisation of D
      glucose or D-galactose containing oligo- and polysaccharides.
AB  - AmyR is commonly considered a regulator of starch degradation whose activity is
      induced by the presence of maltose, the disaccharide building block of starch. In
      this study, we demonstrate that the role of AmyR extends beyond starch
      degradation. Enzyme activity assays, genes expression analysis and growth
      profiling on D-glucose- and D-galactose-containing oligo- and polysaccharides
      showed that AmyR regulates the expression of some of the Aspergillus niger genes
      encoding alpha- and beta-glucosidases, alpha- and beta- galactosidases, as well
      as genes encoding alpha-amlyases and glucoamylases. In addition, we provide
      evidence that D-glucose or a metabolic product thereof may be the inducer of the
      AmyR system in A. niger and not maltose, as is commonly assumed.

PMID- 21874278
TI  - Clinical utilization of postoperative dendritic cell vaccine plus activated T
      cell transfer in patients with intrahepatic cholangiocarcinoma.
AB  - BACKGROUND: The prognosis of patients with intrahepatic cholangiocarcinoma (ICC)
      is extremely poor and the recurrence rate after curative operation is very high.
      There is no standard treatment to prevent recurrence of ICC. In this study, we
      investigated the clinical utilization of a dendritic cell vaccine plus activated
      T-cell transfer in an adjuvant setting for postoperative ICC. METHODS: 36
      patients with ICC were vaccinated at least 3 times with autologous tumor lysate
      pulsed dendritic cells plus ex-vivo activated T-cell transfer. The 5-year
      progression-free survival (PFS) and overall survival (OS) were measured and
      compared with those of 26 patients who received the curative operation alone as a
      concurrent control. The registration number was UMIN000005820. RESULTS: The
      median PFS and OS were 18.3 and 31.9 months in the patients receiving adjuvant
      immunotherapy and 7.7 and 17.4 months in the group receiving surgery alone (p =
      0.005 and 0.022, respectively). In the treated group, patients whose skin
      reactions were 3 cm or more at the vaccine site showed dramatically better
      prognosis (PFS p < 0.001, OS p = 0.001). CONCLUSIONS: A postoperative dendritic
      cell vaccine plus activated T-cell transfer would be a feasible and effective
      treatment for preventing recurrence and achieving long-term survival in ICC
      patients.

PMID- 21874279
TI  - Postoperative adjuvant therapy.
AB  - After a lengthy search for an effective treatment for resected pancreatic cancer,
      evidence accumulated in the past 10 years shows that adjuvant chemotherapy is
      firmly established as offering a modest but real improvement in overall survival.
      However, the optimal choice of treatment modality (chemotherapy with or without
      radiation therapy) remains highly controversial. Results from ongoing studies
      will further optimize the treatment over the next decade. 

PMID- 21874280
TI  - Highly efficient zinc-finger nuclease-mediated disruption of an eGFP transgene in
      keratinocyte stem cells without impairment of stem cell properties.
AB  - Zinc-finger nucleases (ZFNs) are sequence-specific genome engineering tools with
      great potential for the development of gene therapies. The achievement of
      permanent cures through gene therapy requires targeting of stem cells but the
      effects and/or side effects of ZFN treatment on adult stem cell potency are
      largely unknown. Keratinocyte stem cells (KSCs) are attractive candidates for the
      development of gene therapies as their isolation, culture and grafting are well
      established. We derived KSCs from eGFP-transgenic mice and knocked out eGFP
      expression by disrupting the open reading frame with specific ZFNs in cell
      culture. EGFP-negative KSCs were then used as a model system to study the impact
      of ZFN treatment on stem cell potential. We achieved high gene disruption
      efficiencies with up to 18% eGFP-negative KSCs. As expected, ZFN cytotoxicity
      increased with rising ZFN concentrations. However, the ratio of correctly
      targeted KSCs among total treated cells was similar at different ZFN doses. Most
      importantly, our in vitro assays showed that ZFN-treated KSCs maintained their
      stem cell potential. They retained the capacity to both self-renew and form fully
      differentiated epidermal equivalents in culture. Moreover, they were able to form
      spherical aggregates in suspension culture, a characteristic hallmark shared with
      other stem cell types, and they expressed the in vivo KSC markers K15, NFATc1 and
      Sox9. Our data suggest that the stem cell potential of KSCs is not impaired by
      highly efficient ZFN treatment.

PMID- 21874281
TI  - Local injections of adipose-derived mesenchymal stem cells modulate inflammation
      and increase angiogenesis ameliorating the dystrophic phenotype in dystrophin
      deficient skeletal muscle.
AB  - The effects of adipose-derived mesenchymal stem cells (ADMSC) transplantation on
      degeneration, regeneration and skeletal muscle function were investigated in
      dystrophin-deficient mice (24-week-old). ADMSC transplantation improved muscle
      strength and, resistance to fatigue. An increase in fiber cross-sectional area
      and in the number of fibers with centralized nuclei and augment of myogenin
      content were observed. In ADMSC-treated muscles a decrease in muscle content of
      TNF-alpha, IL-6 and oxidative stress measured by Amplex((r)) reagent were
      observed. The level of TGF-beta1 was lowered whereas that of VEGF, IL-10 and IL-4
      were increased by ADMSC treatment. An increase in markers of macrophage M1 (CD11
      and F4-80) and a decrease in T lymphocyte marker (CD3) and arginase-1 were also
      observed in ADMSCs-treated dystrophic muscle. No change was observed in iNOS
      expression. Increased phosphorylation of Akt, p70S6k and 4E-BP1 was found in
      dystrophic muscles treated with ADMSC. These results suggest that ADMSC
      transplantation modulates inflammation and improves muscle tissue regeneration,
      ameliorating the dystrophic phenotype in dystrophin-deficient mice.

PMID- 21874282
TI  - Medical therapy for acute decompensated heart failure: what recent clinical
      trials have taught us about diuretics and vasodilators.
AB  - Diuretics and vasodilators have been the cornerstone of heart failure (HF)
      therapy for decades. Although not shown to reduce mortality, diuretic and
      vasodilator therapy remain commonplace for treating acute decompensated HF, with
      diuretics being the mainstay of therapy for the removal of excess fluid in all
      patients with HF. This article discusses results of recent trials concerning
      diuretic or vasodilator therapy and HF, including the Diuretic Optimization
      Strategies Evaluation (DOSE) trial, the Placebo-Controlled Randomized Study of
      the Selective A1 Adenosine Receptor Antagonist Rolofylline for Patients
      Hospitalized With Acute Decompensated Heart Failure and Volume Overload to Assess
      Treatment Effect on Congestion and Renal Function (PROTECT), and the Efficacy of
      Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST),
      as well as results from the Acute Study of Clinical Effectiveness of Nesiritide
      in Decompensated Heart Failure (ASCEND-HF) trial and the Preliminary Study of
      Relaxin in Acute Heart Failure (Pre-RELAX-AHF).

PMID- 21874283
TI  - What is the role of chemotherapy in endometrial cancer?
AB  - Adjuvant pelvic radiotherapy has the potential to eradicate micrometastases
      within the irradiated field but has not resulted in survival improvements in
      randomized studies. This illustrates the need for systemic therapy. Chemotherapy,
      mainly with anthracyclines, platinum compounds, and taxanes, renders high
      response rates although this unfortunately translates in only modest improvements
      in progression-free and overall survival. Better systemic treatments need to be
      developed. Investigations of the molecular mechanisms of endometrial cancer have
      identified possible targets for therapy. In advanced endometrial cancer one study
      shows that chemotherapy is better than whole abdominal radiotherapy, while in the
      adjuvant situation the combination of chemotherapy and radiotherapy appears
      promising.

PMID- 21874284
TI  - Correlation of aneurysm occlusion with actual metal coverage at neck after
      implantation of flow-diverting stent in rabbit models.
AB  - INTRODUCTION: A remarkable curing rate has been achieved in the treatment of
      intracranial intractable aneurysms by using flow-diverting stents (FDS). An
      appropriate metal coverage (MC) of this device influences the hemodynamics of
      aneurysm significantly but little to branches in vitro. The MC changes after
      elongation or compression and the actual changes are still unknown in vivo. In
      this paper, we analyzed the correlation of aneurysm occlusion with actual MC
      after implantation of FDS in rabbit models. METHODS: FDS was implanted across the
      necks of 22 elastase-induced aneurysms in rabbits. Animals were performed for
      angiography at 4 weeks and sacrificed at 3 months after angiography for
      pathology. Tissue was explanted with stent for micro-computed tomography scan,
      and local shape of stent at neck was reconstructed. Actual MC at neck was
      calculated, and the correlations of aneurysm occlusion with effective factors
      were analyzed. RESULTS: Greater than 95% angiographic aneurysm occlusion rates
      for the FDS, which covered the neck of aneurysms, were 61.9% at 4 weeks and 57.9%
      by angiography at 3 months. Aneurysm occlusion was positively correlated with
      local MC of stent at neck (r (s) = 0.486; P = 0.026). A 35% actual MC at the neck
      predicted greater than 95% angiographic aneurysm occlusion with a specificity of
      100% and sensitivity of 53.8%. CONCLUSION: Aneurysm occlusion was positively
      correlated with local MC of stent at the neck. The FDS with 35% MC can predict
      greater than 95% angiographic aneurysm occlusion.

PMID- 21874285
TI  - Cinacalcet lowers FGF-23 level together with bone metabolism in hemodialyzed
      patients with secondary hyperparathyroidism.
AB  - PURPOSE: Secondary hyperparathyroidism (sHPT) is associated with elevated levels
      of FGF-23, which in turn are connected to adverse outcomes in ESRD patients. The
      relationship between FGF-23 and bone metabolism in patients with sHPT treated
      with cinacalcet has not been studied. METHODS: Thirty-four stable chronically
      hemodialyzed patients with sHPT were prospectively followed during the treatment
      with cinacalcet without any changes in concurrent vitamin D or phosphate binder
      dose. Blood samples were collected at the start and after 6 months of study.
      Levels of osteocalcin (OC), cross-linked C-telopeptide of type I collagen (CTX),
      and FGF-23 were measured. RESULTS: Eighteen patients finished the study. Levels
      of calcium, phosphate, and iPTH decreased during 6 months of treatment with
      cinacalcet. Serum level of FGF-23 decreased significantly (log FGF-23 from 7.58
      +/- 1.7 to 6.61 +/- 1.7 pg/ml) (P < 0.001). Cinacalcet lowered the concentration
      of CTX from 3.1 +/- 0.6 ng/ml to 2.6 +/- 0.9 ng/ml (P < 0.05) and OC from 91.8
      (41.5-558.6) to 70.3 (11.3-419.7) ng/ml (P < 0.05). The magnitude of change in
      FGF-23 concentration before and after treatment correlated significantly with
      suppression of osteoblasts' function assessed by DeltaOC (r = 0.5, P < 0.05) but
      not with changes in bone resorption marker DeltaCTX. CONCLUSIONS: Cinacalcet
      treatment of sHPT results in reduction of FGF-23 levels, probably due to the
      suppression of osteoblasts function.

PMID- 21874286
TI  - Inefficient use of inverted pendulum mechanism during quadrupedal walking in the
      Japanese macaque.
AB  - In animal walking, the gravitational potential and kinetic energy of the center
      of mass (COM) fluctuates out-of-phase to reduce the energetic cost of locomotion
      via an inverted pendulum mechanism, and, in canine quadrupedal walking, up to 70%
      of the mechanical energy can be recovered. However, the rate of energy recovery
      for quadrupedal walking in primates has been reported to be comparatively lower.
      The present study analyzed fluctuations in the potential and kinetic energy of
      the COM during quadrupedal walking in the Japanese macaque to clarify the
      mechanisms underlying this inefficient utilization of the inverted pendulum
      mechanism in primates. Monkeys walked on a wooden walkway at a self-selected
      speed, and ground reaction forces were measured, using a force platform, to
      calculate patterns of mechanical energy fluctuation and rates of energy recovery.
      Our results demonstrated that rates of energy recovery for quadrupedal walking in
      Japanese macaques were approximately 30-50%, much smaller than those reported for
      dogs. Comparisons of the patterns of mechanical energy fluctuation suggested that
      the potential and kinetic energies oscillated relatively more in-phase, and
      amplitudes did not attain near equality during quadrupedal walking in Japanese
      macaques, possibly because of greater weight support (reaction force) of the
      hindlimbs and more protracted forelimbs at touchdown in the Japanese macaque, two
      of the three commonly accepted locomotor characteristics distinguishing primates
      from non-primate mammals.

PMID- 21874288
TI  - Spectroscopic identification of interactions of Pb2+ with bovine serum albumin.
AB  - The effect of Pb(2+) targeted to bovine serum albumin (BSA) in vitro was
      investigated by fluorescence, synchronous fluorescence, UV absorption and
      circular dichroism (CD) spectrophotometry. The characteristic fluorescence of BSA
      was quenched, which indicated that Pb(2+) changed the skeleton of BSA and caused
      the gradual exposure of aromatic amino acid residues (Trp, Tyr, Phe) in the
      internal hydrophobic region of BSA. When the concentration of Pb(2+) was higher
      than 1 * 10(-4) mol/L, the BSA was completely denatured. The excess lead ion
      interacted with the aromatic amino acid residues of BSA exposed to the solution,
      which decreased the fluorescence of BSA further. According to the experiment
      results, we found that a lead-BSA complex was formed following static quenching
      and the binding site was calculated approximately equal to 1. This work reflected
      the interaction mechanism of BSA and Pb(2+) from the perspective of spectroscopy.

PMID- 21874289
TI  - Anti-cancer actions of denosumab.
AB  - Denosumab works by binding to and inhibiting receptor activator of nuclear factor
      kappaB ligand (RANKL). Through this mechanism, it can inhibit any cause of bone
      destruction and thus shows great efficacy in high-turnover osteoporosis. The
      FREEDOM (Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6
      Months) trial established the effectiveness of denosumab as a therapy for
      menopausal bone loss, whereas several newer trials have found denosumab to have
      shown denosumab to be beneficial in preventing skeletal events from bone
      metastases. This review highlights the potential novel anti-cancer mechanisms of
      action of denosumab in mammary tumors.

PMID- 21874290
TI  - The effects of smoke carcinogens on bone.
AB  - The greatest cause of preventable morbidity and mortality is smoking, and one of
      the often-underappreciated effects of smoking is profound bone loss. The existing
      clinical paradigm for smoking is that there is a low turnover osteoporosis. This
      review highlights findings from recent clinical trials and animal research
      demonstrating either support or conflict with the existing paradigm. Clinically,
      it is noted that markers of bone formation are often normal in smokers; these
      clinical findings conflict with well-conducted animal research demonstrating that
      carcinogens acting on the aryl hydrogen receptor can significantly reduce
      osteoblast formation and function. Regarding bone resorption, highlights from
      recent clinical studies suggest that bone remodeling is increased in smokers.
      Directly contradicting this enhanced osteoclastogenesis are several animal
      studies all demonstrating significant inhibition of osteoclast formation and
      function upon exposure to smoke carcinogens. Future research is needed to clarify
      whether smoking is truly a low bone remodeling osteoporosis, or an osteoclast
      driven bone destruction, with inappropriately normal bone formation.

PMID- 21874292
TI  - Minimally invasive lateral transpsoas approach with advanced neurophysiologic
      monitoring for lumbar interbody fusion.

PMID- 21874291
TI  - Validation of organotypical hippocampal slice cultures as an ex vivo model of
      brain ischemia: different roles of NMDA receptors in cell death signalling after
      exposure to NMDA or oxygen and glucose deprivation.
AB  - N-Methyl-D-aspartate receptors (NMDARs) are essential mediators of synaptic
      plasticity under normal physiological conditions. During brain ischemia, these
      receptors are excessively activated due to glutamate overflow and mediate
      excitotoxic cell death. Although organotypical hippocampal slice cultures are
      widely used to study brain ischemia in vitro by induction of oxygen and glucose
      deprivation (OGD), there is scant data regarding expression and functionality of
      NMDARs in such slice cultures. Here, we have evaluated the contribution of NMDARs
      in mediating excitotoxic cell death after exposure to NMDA or OGD in
      organotypical hippocampal slice cultures after 14 days in vitro (DIV14). We found
      that all NMDAR subunits were expressed at DIV14. The NMDARs were functional and
      contributed to cell death, as evidenced by use of the NMDAR antagonist MK-801
      (dizocilpine). Excitotoxic cell death induced by NMDA could be fully antagonized
      by 10 MUM MK-801, a dose that offered only partial protection against OGD-induced
      cell death. Very high concentrations of MK-801 (50-100 MUM) were required to
      counteract cell death at long delays (48-72 h) after OGD. The relative high dose
      of MK-801 needed for long-term protection after OGD could not be attributed to
      down-regulation of NMDARs at the gene expression level. Our data indicate that
      NMDAR signaling is just one of several mechanisms underlying ischemic cell death
      and that prospective cytoprotective therapies must be directed to multiple
      targets.

PMID- 21874293
TI  - Esophagus perforation complicating anterior cervical spine surgery.
AB  - PURPOSE: To study the diagnosis and treatment strategy of esophagus perforation
      complicating anterior cervical spine surgery. METHODS: From 2000 to 2010, we
      performed 1,045 cases of anterior cervical surgeries. One developed esophagus
      perforation. The diagnosis and treatment strategy of this case and the other five
      patients with esophagus perforation from other hospitals were retrospectively
      reviewed. For an intraoperative perforation, primary double layer suture was
      performed. Postoperatively, the patient took nutrition by a nasogastric tube
      instead of oral intake for one week. For three cases of perforations early in the
      post-operative period, oral intake was forbidden and nasogastric tube was
      conducted for nutrition support. The wound was debrided and open drainage was
      conducted postoperatively. Intravenous broad-spectrum antibiotic therapy was
      utilized. For perforations at postoperative year 3 and 7, prohibition of oral
      intake, intravenous broad-spectrum antibiotics therapy, and nasogastric tube
      nutrition support were all conducted and surgical debridement was performed. In
      operation, fixation plates and screws were removed, and the edges of the
      perforation were loosely approximated by synthetic absorbable sutures.
      Postoperatively, skin wound was kept open for drainage. RESULTS: All the
      perforations healed evenly without secondary complications. CONCLUSIONS: When a
      perforation is suspected, imaging techniques should be employed. Surgical
      treatment facilitates the healing of esophagus perforation. Supportive treatments
      including prohibition of oral intake, intravenous broad-spectrum antibiotic
      therapy, feeding with a nasogastric tube were mandatory parts of treatments.

PMID- 21874294
TI  - Surgical treatment of spontaneous intracranial hypotension secondary to
      degenerative cervical spine pathology: a case report and literature review.
AB  - OBJECTIVE AND IMPORTANCE: A rare cause of intracranial hypotension is leakage of
      cerebrospinal fluid (CSF) through a dural breach from degenerative cervical spine
      pathology. To our knowledge there have been only four cases described in the
      English literature. Treatment is challenging and varies from case to case, with
      complete symptom resolution reported for only one patient. Herein we review the
      literature and describe our surgical management of a 46-year-old woman with
      symptomatic intracranial hypotension from the penetration of the cervical thecal
      sac. CLINICAL PRESENTATION: The patient presented with a 3-month history of
      progressive orthostatic headaches. Magnetic resonance imaging demonstrated
      bilateral subdural hematomas and pachymeningeal gadolinium enhancement. An
      anterior epidural CSF collection commencing at a C4-5 calcified disc protrusion
      and osteophyte was evident on a computed tomography spinal myelogram.
      INTERVENTION: After three unsuccessful lumbar blood patches, we elected to
      attempt surgical removal of the causative pathology with exposure and primary
      closure of the dural defect by anterior cervical discectomy as described
      previously. After resection of the disc-osteophyte complex and dural exposure,
      immediate high volume egression of CSF mixed with blood at the surgical site. The
      dural defect was not visible but CSF egression promptly ceased. Cervical
      corpectomy for greater exposure and primary repair of the defect has been
      described, but we considered this unwarranted and felt the intraoperative blood
      collection formed a local blood patch. A collagen dural substitute membrane was
      inserted through the discectomy space for reinforcement. CONCLUSION: Two months
      after this novel surgical blood patch procedure the patient was asymptomatic and
      follow-up imaging demonstrated complete resolution.

PMID- 21874295
TI  - Injectable thermoreversible hyaluronan-based hydrogels for nucleus pulposus cell
      encapsulation.
AB  - INTRODUCTION: Thermoreversible hydrogels have potential in spine research as they
      provide easy injectability and mild gelling mechanism (by physical cross-link).
      The purpose of this study was to assess the potential of thermoreversible
      hyaluronan-based hydrogels (HA-pNIPAM) (pNIPAM Mn = 10, 20, 35 * 10(3) g mol(-1))
      as nucleus pulposus cells (NPC) carrier. MATERIALS AND METHODS: Cytocompatibility
      (WST-1 assay), viability (trypan blue), morphology (toluidine blue), sulphated
      glycosaminoglycan synthesis (DMMB assay) and gene expression profile (real-time
      PCR) of bovine NPC cultured in HA-pNIPAM were followed for 1 week and compared to
      alginate gel bead cultures. The injectability and cell survival in a whole disc
      organ culture model were assessed up to day 7. RESULTS: All HA, HA-pNIPAM and
      their degradation products were cytocompatible to NPC. HA-pNIPAM hydrogels with
      no volume change upon gelling maintained NPC viability and characteristic rounded
      morphology. Glycosaminoglycan synthesis was similar in HA-pNIPAM and alginate
      gels. Following NPC expansion, both gels induced re-differentiation toward the
      NPC phenotype. Significant differences between the two gels were found for COLI,
      COLII, HAS1, HAS2 and ADAMTS4 but not for MMPs and TIMPs. Higher expression of
      hyaluronan synthases (HAS1, HAS2) and lower expression of COLI and COLII mRNA
      were noted in cells cultured in HA-pNIPAM (pNIPAM = 20 * 10(3)g mol(-1)). NPC
      suspension in HA-pNIPAM was injectable through a 22-G needle without loss of cell
      viability. Ex vivo, NPC viability was maintained in HA-pNIPAM for 1 week.
      CONCLUSION: A HA-pNIPAM composition suitable for nucleus pulposus repair that
      provides an injectable carrier for NPC, maintains their phenotype and promotes
      extracellular matrix generation was identified.

PMID- 21874296
TI  - Neurocritical care for neonates.
AB  - OPINION STATEMENT: Neurocritical care is an emerging subspecialty that combines
      expertise in neurology, critical care medicine, neuroradiology, and neurosurgery.
      Increasing evidence from the adult literature suggests that specialized
      neurocritical care can lead to improved outcomes following acute brain injury.
      Critically ill neonates with neurologic conditions may also benefit from
      specialized neurocritical care. Adherence to guidelines and managing patients in
      intensive care nurseries with dedicated, multidisciplinary neurocritical care
      personnel may optimize outcomes. This goal may be achieved by more quickly
      recognizing neurologic impairment, preventing secondary brain injury by
      maintaining basic physiologic functions, and rapidly implementing therapies.
      Nurseries that care for neonates with suspected acute brain injury should be
      prepared to adequately support multiorgan involvement, monitor the brain to
      detect seizures, evaluate for brain injury using MRI, and follow development
      through school age.

PMID- 21874297
TI  - Mitochondrial ATP synthase: architecture, function and pathology.
AB  - Human mitochondrial (mt) ATP synthase, or complex V consists of two functional
      domains: F(1), situated in the mitochondrial matrix, and F(o), located in the
      inner mitochondrial membrane. Complex V uses the energy created by the proton
      electrochemical gradient to phosphorylate ADP to ATP. This review covers the
      architecture, function and assembly of complex V. The role of complex V di-and
      oligomerization and its relation with mitochondrial morphology is discussed.
      Finally, pathology related to complex V deficiency and current therapeutic
      strategies are highlighted. Despite the huge progress in this research field over
      the past decades, questions remain to be answered regarding the structure of
      subunits, the function of the rotary nanomotor at a molecular level, and the
      human complex V assembly process. The elucidation of more nuclear genetic defects
      will guide physio(patho)logical studies, paving the way for future therapeutic
      interventions.

PMID- 21874298
TI  - Redox-proteomics of the effects of homogentisic acid in an in vitro human serum
      model of alkaptonuric ochronosis.
AB  - Alkaptonuria (AKU) is a rare inborn error of metabolism associated with a
      deficient activity of homogentisate 1,2-dioxygenase (HGO), an enzyme involved in
      tyrosine and phenylalanine metabolism. Such a deficiency leads to the
      accumulation of homogentisic acid (HGA) and its oxidized/polymerized products in
      connective tissues, where melanin-like pigments accumulate (ochronosis).
      Ochronosis involves especially joints, where an ochronotic arthropathy develops.
      Little is known on the molecular mechanisms leading to ochronosis and ochronotic
      arthropathy in AKU. Previous works of ours showed that HGA in vitro propagates
      oxidative stress through its conversion into benzoquinone acetate (BQA). We hence
      used an in vitro model consisting of human serum treated with HGA and evaluated
      the activities of glutathione related anti-oxidant enzymes and levels of
      compounds indexes of oxidative stress. Proteomics and redox-proteomics were used
      to identify oxidized proteins and proteins more likely able to bind BQA. Overall,
      we found that the production of ochronotic pigment in HGA-treated serum is
      accompanied by lipid peroxidation, decreased activity of the enzyme glutathione
      peroxidase and massive depletion of thiol groups, together with increased protein
      carbonylation and thiol oxidation. We also found that BQA was likely to bind
      carrier proteins and naturally abundant serum proteins, eventually altering their
      chemico-physical properties. Concluding, our work points towards a critical
      importance of thiol compounds in counteracting HGA- and BQA- mediated stress in
      AKU, so that future research for disease biomarkers and pharmacological
      treatments for AKU and ochronosis will be more easily addressed.

PMID- 21874299
TI  - Blocking TNF-alpha with infliximab alleviates ovariectomy induced mechanical and
      thermal hyperalgesia in rats.
AB  - Studies have proved an increased expression of tumor necrosis factor alpha (TNF
      alpha) in estrogen deficiency animals, and TNF-alpha also plays a role in
      inflammation and neuropathic pain. This study aimed to explore the relationship
      between TNF-alpha and ovariectomy induced hyperalgesia. 36 female Sparague-Dawley
      were included, estrogen depletion models were established by ovariectomy. Then
      infliximab (a TNF-alpha blocker) was administrated to the ovariectomized rats for
      8 weeks. Pain behavioral tests were performed once a week. The bone mineral
      density (BMD), serum estradiol and TNF-alpha level were determined at the 8th
      week after ovariectomy. The expression of TNF-alpha in lumbar 5 dorsal root
      ganglions (L5 DRGs) was examined by immunofluorescence method. Significant
      hyperalgesia to mechanical and thermal stimuli in groups Ovx-1 and Ovx-2 was
      observed 1 week after the operation. After treated with infliximab, the pain
      threshold of Ovx-2 was partially restored, although still lower than the Sham
      group. The serum TNF-alpha level of Ovx-1 was significantly higher than Sham and
      Ovx-2. TNF-alpha immunofluorescence indicated a significant increase in the
      expression of TNF-alpha at L5 DRGs in group Ovx-1 when compared with groups Sham
      and Ovx-2. The BMD of group Ovx-2 was significantly higher than group Ovx-1 and
      lower than group Sham. In conclusion, TNF-alpha plays an important role in
      estrogen deficiency induced mechanical and thermal hyperalgesia, and DRG may be
      one site on which TNF-alpha acts to cause hyperalgesia. Blocking the effect of
      TNF-alpha could partially alleviate the estrogen deficiency induced hyperalgesia
      in rats. Thus, TNF-alpha may contribute to chronic pain in postmenopausal women.

PMID- 21874300
TI  - Brain tuberculoma (Mycobacterium africanum): high index of suspicion helps in
      avoiding biopsy/surgery.
AB  - Partial seizures can be due to a growing cerebral lesion, which may be tumoral or
      inflammatory/infectious in nature. The differential diagnosis is obviously
      important; increasing immigration to Europe from Africa is leading to an increase
      of infectious disease involving also the central nervous system. The authors
      report imaging the a case of a brain tuberculoma due to Mycobacterium africanum
      mimicking brain tumor, in which diagnosis was possible by inoculum in guinea-pig
      of material obtained by mediastinal biopsy of enlarged lymph nodes. Specific
      treatment led to marked reduction in the size of the brain lesion.

PMID- 21874301
TI  - Peripheral neuropathy and lower limb swelling caused by a giant popliteal fossa
      hematoma.

PMID- 21874302
TI  - The immune inhibitory receptor osteoactivin is upregulated in monocyte-derived
      dendritic cells by BCR-ABL tyrosine kinase inhibitors.
AB  - Multiple approaches presently aim to combine targeted therapies using tyrosine
      kinase inhibitors with immunotherapy. Ex vivo-generated dendritic cells are
      frequently used in such strategies due to their unique ability to initiate
      primary T-cell immune responses. Besides governing tumor cell growth, many
      kinases targeted by tyrosine kinase inhibitors are involved in the development
      and function of dendritic cells and thus tyrosine kinase inhibitor therapy may
      cause immunoinhibitory side effects. We here report that exposure of developing
      human monocyte-derived dendritic cells to the BCR-ABL inhibitors imatinib,
      dasatinib, and nilotinib results in profound upregulation of the transmembrane
      glycoprotein osteoactivin that has recently been characterized as a negative
      regulator of T-cell activation. Thus, in line with osteoactivin upregulation,
      exposure to tyrosine kinase inhibitors resulted in significantly reduced
      stimulatory capacity of dendritic cells in mixed lymphocyte reactions that could
      be restored by the addition of blocking anti-osteoactivin antibody. Our data
      demonstrate that tyrosine kinase inhibitor-mediated inhibition of dendritic cell
      function is, at least in great part, mediated by upregulation of the immune
      inhibitory molecule osteoactivin.

PMID- 21874303
TI  - Human kallikrein 4 signal peptide induces cytotoxic T cell responses in healthy
      donors and prostate cancer patients.
AB  - Immunotherapy is a promising new treatment for patients with advanced prostate
      and ovarian cancer, but its application is limited by the lack of suitable target
      antigens that are recognized by CD8+ cytotoxic T lymphocytes (CTL). Human
      kallikrein 4 (KLK4) is a member of the kallikrein family of serine proteases that
      is significantly overexpressed in malignant versus healthy prostate and ovarian
      tissue, making it an attractive target for immunotherapy. We identified a
      naturally processed, HLA-A*0201-restricted peptide epitope within the signal
      sequence region of KLK4 that induced CTL responses in vitro in most healthy
      donors and prostate cancer patients tested. These CTL lysed HLA-A*0201+ KLK4 +
      cell lines and KLK4 mRNA-transfected monocyte-derived dendritic cells. CTL
      specific for the HLA-A*0201-restricted KLK4 peptide were more readily expanded to
      a higher frequency in vitro compared to the known HLA-A*0201-restricted epitopes
      from prostate cancer antigens; prostate-specific antigen (PSA), prostate-specific
      membrane antigen (PSMA) and prostatic acid phosphatase (PAP). These data
      demonstrate that KLK4 is an immunogenic molecule capable of inducing CTL
      responses and identify it as an attractive target for prostate and ovarian cancer
      immunotherapy.

PMID- 21874304
TI  - Exposure of CD34+ precursors to cytostatic anthraquinone-derivatives induces
      rapid dendritic cell differentiation: implications for cancer immunotherapy.
AB  - Appropriate activation of dendritic cells (DC) is essential for successful active
      vaccination and induction of cell-mediated immunity. The scarcity of precursor
      cells, as well as long culture methods, have hampered wide-scale application of
      DC vaccines derived from CD34(+) precursors, despite their suggested superior
      efficacy over the more commonly applied monocyte-derived DC (MoDC). Here,
      employing the CD34(+)/CD14(+) AML-derived human DC progenitor cell line MUTZ3, we
      show that cytostatic anthraquinone-derivatives (i.e., the anthracenedione
      mitoxantrone and the related anthracyclin doxorubicin) induce rapid
      differentiation of CD34(+) DC precursors into functional antigen-presenting cells
      (APC) in a three-day protocol. The drugs were found to act specifically on
      CD34(+), and not on CD14(+) DC precursors. Importantly, these observations were
      confirmed for primary CD34(+) and CD14(+) DC precursors from peripheral blood.
      Mitoxantrone-generated DC were fully differentiated within three days and after
      an additional 24 h of maturation, were as capable as standard 9-day
      differentiated and matured DC to migrate toward the lymph node-homing chemokines
      CCL19 and CCL21, to induce primary allogeneic T cell proliferation, and to prime
      functional MART1-specific CD8(+) T lymphocytes. Our finding that anthraquinone
      derivatives like mitoxantrone support rapid high-efficiency differentiation of DC
      precursors may have consequences for in vitro production of DC vaccines as well
      as for novel immunochemotherapy strategies.

PMID- 21874305
TI  - Hyperactivity/inattention problems moderate environmental but not genetic
      mediation between negative parenting and conduct problems.
AB  - This study investigated the association between negative parenting (NP) and
      conduct problems (CP) in 6-year-old twins, taking into account the severity of
      hyperactivity/inattention problems (HIAP). Analyses of the data from 1,677 pairs
      of twins and their parents revealed that the shared environmental covariance
      between NP and CP was moderated by the level of HIAP but not by CP or NP, where
      the shared environmental covariance was larger in children with higher levels of
      HIAP than in children with lower levels of HIAP. The genetic covariance between
      NP and CP was not moderated by the level of HIAP, whereas it was larger in the
      group with lower levels of CP and NP than in the group with higher levels. These
      results suggest that severe HIAP strengthens shared environmental associations
      between NP and CP and that interventions focusing on the shared environmental
      component of NP would be effective for parents and children with severe HIAP.

PMID- 21874306
TI  - A case of developmental glaucoma suspected from megalophthalmos represented by
      obstetric ultrasonography.

PMID- 21874307
TI  - Efficacy and safety of tafluprost in normal-tension glaucoma with intraocular
      pressure of 16 mmHg or less.
AB  - PURPOSE: To evaluate the intraocular pressure (IOP)-reducing effects and safety
      of 0.0015% tafluprost ophthalmic solution (tafluprost) in normal-tension glaucoma
      (NTG) patients with an IOP of 16 mmHg or less. METHODS: NTG patients with a
      baseline IOP of 16 mmHg or less were enrolled for a one-eye study in which
      tafluprost was applied once daily for 12 weeks. The presence of adverse drug
      reactions and the cumulative incidence of adverse events were also investigated.
      RESULTS: Among the 44 enrolled patients, 41/44 (93.2%) eyes completed the study.
      The baseline IOP was 13.2 +/- 1.3 mmHg in the study eyes and 13.0 +/- 1.3 mmHg in
      the fellow eyes, which was not statistically significant (P = 0.9173, Student's t
      test). The values obtained for IOP in the study eyes versus fellow eyes were 10.2
      +/- 1.6 versus 12.1 +/- 1.5 mmHg at week 12. The IOP difference between the study
      eyes and the fellow eyes was statistically significant (P < 0.0001, Student's t
      test). The cumulative incidence of adverse events was 58.5% by week 12. Ocular
      itching was the most frequently observed adverse event (29.3%). All adverse
      events were clinically tolerable. CONCLUSIONS: Tafluprost induced significant IOP
      reductions in NTG patients with a baseline IOP of 16 mmHg or less without raising
      any safety concerns.

PMID- 21874308
TI  - Correlation between cross-sectional shape of choroidal veins and choroidal
      thickness.
AB  - PURPOSE: To determine whether a significant correlation exists between the ratio
      of the vertical and horizontal diameters of the choroidal veins and the choroidal
      thickness in normal eyes. METHODS: Six clinic-based normal eyes were studied. The
      macula and retina around the optic disc were examined by spectral-domain optical
      coherence tomography (OCT) during indocyanine green angiography (IA), and
      choroidal thickness maps were constructed. The vertical and horizontal diameters
      of the choroidal veins in the OCT images and horizontal diameters in the IA
      images in the venous phase were measured at 12 locations of different choroidal
      thickness. The horizontal diameter of the choroidal veins measured in the OCT
      images and the corresponding IA images were compared, and the correlation between
      the ratio of the vertical and horizontal diameters of the choroidal veins and the
      corresponding choroidal thickness was determined. RESULTS: The horizontal
      diameters of the choroidal veins measured in IA and OCT images were not
      significantly different and were significantly correlated (r = 0.73; P < 0.01).
      The ratio of the vertical and horizontal diameters of the choroidal veins was
      significantly correlated with the choroidal thickness (r = 0.85; P < 0.001).
      CONCLUSION: The significant correlation between the ratio of the vertical and
      horizontal diameters of the veins to the choroidal thickness should be considered
      when the cross-sectional area of the choroidal veins is evaluated.

PMID- 21874309
TI  - Evaluation of the relationship between background factors and sleep-disordered
      breathing in patients with proliferative diabetic retinopathy.
AB  - PURPOSE: To clarify the relationship between sleep-disordered breathing (SDB) and
      background factors in patients with proliferative diabetic retinopathy (PDR).
      PARTICIPANTS AND METHODS: One hundred fifty-one consecutive PDR patients were
      included in this study. These patients' SDB parameters, including the mean and
      lowest SpO(2), sleeping 4% oxygen desaturation index (ODI), and cumulative
      percentage of time spent at SpO(2) < 90% (CT90%), were measured. Simple linear
      regression analyses were conducted to investigate whether the SDB parameters
      correlated with systemic factors for PDR, including age, duration of diabetes,
      HbA1c value, incidence of hypertension, estimated glomerular filtration rate
      (eGFR), body mass index (BMI), and insulin therapy. Logistic regression analysis
      was also conducted to investigate whether the SDB evaluation items were factors
      independently associated with the incidence of hypertension. RESULTS:
      Hypertension and BMI were statistically correlated with all of the parameters.
      The eGFR was statistically correlated with 4% ODI and insulin therapy with the
      lowest SpO(2). Logistic regression analysis revealed 4% ODI and eGFR as factors
      independently contributing to the incidence of hypertension. CONCLUSION: The
      results of our study confirmed the relationship between SDB and background
      factors reported to be risk factors for diabetic retinopathy progression in
      patients with PDR.

PMID- 21874310
TI  - Disease-free probability after the first primary ductal carcinoma in situ of the
      breast: a comparison between African-American and White-American women.
AB  - Compelling evidence about the differences in the biology and behavior of invasive
      breast cancer between African-American (AA) and White-American (WA) women
      motivate inquiry into comparing the clinicopathology of non-invasive breast
      cancer (ductal carcinoma in situ, DCIS). AA and WA women diagnosed with their
      first primary DCIS between 1990 and 1999 were identified from the institutional
      tumor registry. Data on method of presentation, treatment, and patient
      characteristics were retrieved from electronic medical records. Patients were
      followed up through the medical records until the diagnosis of a subsequent
      cancer or the last day of contact with the institution. A total of 100 (29.6%)
      AAs and 236 (70.4%) WAs with the mean age of 60 (SD +/- 13) and 57 (SD +/- 12),
      respectively, contributed to this study. DCIS was detected during routine
      screening mammography for 81% (n = 81) of AAs and 88.4% (n = 206) of WAs (P =
      0.073). Differences in the distributions of grade, margin status, necrosis, or
      treatment modalities were not statistically significant between AAs and WAs.
      Analysis of competing risks Cox proportional hazard multivariate modeling yielded
      a significant 8-year cumulative risk of a second cancer for AAs but only in the
      ipsilateral breast (HR = 3.96, 95% CI 1.42-11.04, P = 0.01). Despite comparable
      clinical presentation and treatment, 8 years after the initial treatment, AAs
      experienced a higher risk of second breast cancer in ipsilateral but not in the
      contralateral breast. The observed excess risk of a second cancer in the
      ipsilateral breast may suggest of intrinsic differences in the biology of cancer.

PMID- 21874311
TI  - Are genetic and environmental components of variance in mammographic density
      measures that predict breast cancer risk independent of within-twin pair
      differences in body mass index?
AB  - To understand the role of mammographic density on breast cancer risk, it is
      important to take into account body mass index (BMI). As with age, BMI is
      negatively confounded with mammographic density, and a previous US twin study
      found that the covariance structure of mammographic density depended on the
      extent to which pairs differ in BMI. Using a computerised thresholding technique,
      we measured mammographic dense area for 571 monozygous (MZ) and 380 dizygous (DZ)
      twin pairs aged 40-70 years from Australia and North America. After adjusting for
      age and BMI, we calculated estimates of variance, covariance, correlation and,
      under the assumptions of the classic twin model, additive genetic (A), common
      environment (C) and person-specific environmental (E) components of variance.
      Analyses were conducted both within and across categories of within-pair
      differences in BMI, under a bivariate normal model using the software FISHER. The
      variance, MZ and DZ correlations, and the differences between MZ and DZ
      correlations and covariances were not constant across absolute within-pair
      differences in BMI (for the DZ correlation, P = 0.04, all other P < 0.001). No
      model involving a combination of one or more of A, C and E gave an acceptable
      fit. The interpretation of these observations is not straightforward. They, and
      other data, challenge the assumptions of the classic twin model for mammographic
      density and suggest that an insightful test of those assumptions can be made by
      testing the stability of correlations, covariances and variance components across
      absolute within-pair differences in potential mediators.

PMID- 21874312
TI  - Survival-adjusted health-related quality of life (HRQL) among patients with
      metastatic breast cancer receiving paclitaxel plus bevacizumab versus paclitaxel
      alone: results from Eastern Cooperative Oncology Group Study 2100 (E2100).
AB  - The purpose of this study was to examine health-related quality of life (HRQL)
      among women with metastatic breast cancer treated on E2100 with paclitaxel or
      paclitaxel plus bevacizumab. Trial participants (N = 670) completed the
      Functional Assessment of Cancer Therapy-Breast (FACT-B) pre-treatment and
      following 4 and 8 cycles of treatment to assess HRQL and breast cancer-specific
      concerns. A significantly higher proportion of missing FACT-B assessments was
      observed among patients receiving paclitaxel only, due to faster time to death.
      To account for this non-ignorable pattern of missing data, we conducted a
      survival-adjusted HRQL analysis by jointly modeling the longitudinal HRQL outcome
      and time to non-ignorable dropout using a two-stage model. FACT scores assessing
      HRQL did not differ following 4 and 8 cycles of treatment; however mean scores on
      the 9-item Breast Cancer Scale were significantly higher after 4 and 8 cycles of
      treatment among patients receiving paclitaxel plus bevacizumab. No differences
      were observed between treatment arms on FACT-B total scores. The addition of
      bevacizumab was not associated with additional side effect burden from the
      patient perspective and was associated with a greater reduction in breast cancer
      specific concerns. No other differences were noted.

PMID- 21874313
TI  - A comparison of the FACT-G and the Supportive Care Needs Survey (SCNS) in women
      with ovarian cancer: unidimensionality of constructs.
AB  - PURPOSE: Health-related quality of life (HRQoL) and unmet needs (needs)
      questionnaires offer alternative perspectives for assessing cancer patients'
      concerns. We examined whether the conceptual differences underlying these
      alternative approaches yield corresponding empirical differences. METHODS: Eight
      hundred and seventy-four women with ovarian cancer completed the Functional
      Assessment of Cancer Therapy scale (FACT-G; HRQoL) and the Supportive Care Needs
      Survey (SCNS-SF34; needs) every 3 months for 2 years. Correlational analysis,
      exploratory and confirmatory factor analysis (EFA/CFA), and Rasch analysis tested
      the relationship between patients' responses to similar domains and similar items
      across the two questionnaires. RESULTS: Strong correlations were found between
      items with virtually identical wording (0.67-0.75), while moderate to strong
      correlations (0.55-0.65) were found for those with very similar wording. EFA
      identified two common domains across the two questionnaires: physical and
      psychological. For each common domain, CFA indicated models involving a single
      construct with systematic variation within each questionnaire fit best. Rasch
      analysis including very similar items within the physical and psychological
      domains (separately) demonstrated strong evidence of unidimensionality.
      CONCLUSIONS: The high degree of similarity between patient responses to items
      addressing the same or very similar concerns suggests either that HRQoL and needs
      approaches do not reflect different constructs or that patients may not be able
      to differentiate between the severity of a concern and the level of need
      associated with that concern, especially when these are assessed in quick
      succession.

PMID- 21874314
TI  - Neuro-QOL: quality of life item banks for adults with neurological disorders:
      item development and calibrations based upon clinical and general population
      testing.
AB  - PURPOSE: Neuro-QOL provides a clinically relevant and psychometrically robust
      health-related quality of life (HRQL) assessment tool for both adults and
      children with common neurological disorders. We now report the psychometric
      results for the adult tools. METHODS: An extensive research, survey and consensus
      process was used to produce a list of 5 priority adult neurological conditions
      (stroke, multiple sclerosis, Parkinson's disease, epilepsy and ALS). We
      identified relevant health related quality of life (HRQL) domains through
      multiple methods and data sources including a comprehensive review of the
      literature and literature search, expert interviews and surveys and patient and
      caregiver focus groups. The final domain framework consisted of 17 domains of
      Physical, Mental and Social health. There were five phases of item development:
      (1) identification of 3,482 extant items, (2) item classification and selection,
      (3) item review and revision, (4) cognitive interviews with 63 patients to assess
      their understanding of individual items and (5) field testing of 432
      representative items. PARTICIPANTS AND PROCEDURES: Participants were drawn from
      the US general population and clinical settings, and included both English and
      Spanish speaking subjects (N = 3,246). Confirmatory factor analysis (CFA) was
      used to evaluate the dimensionality of unidimensional domains. Where the domain
      structure was previously unknown, the dataset was split and first analyzed with
      exploratory factor analysis and then CFA. Samejima's graded response model (GRM)
      was used to calculate IRT parameters. We further evaluated differential item
      functioning (DIF) on gender, education and age. RESULTS: Thirteen unidimensional
      calibrated item banks consisting of 297 items were developed. All of the tested
      item banks had high reliability and few or no locally dependent items. The range
      of item slopes and thresholds with good information are reported for each of the
      item banks. The banks can support CAT and the development of short forms.
      CONCLUSION: The Neuro-QOL measurement system provides item banks and short forms
      that enable PRO measurement in neurological research, minimizes patient burden
      and can be used to create multiple instrument types minimizing standard error.
      The 17 adult measures include 13 calibrated item banks, 3 item pools available
      for calibration work by others, and 1 stand-alone scale (index). The Neuro-QOL
      instruments provide a "common metric" of representative concepts for use across
      patient groups in different studies.

PMID- 21874315
TI  - The intact strontium ranelate complex stimulates osteoblastogenesis and
      suppresses osteoclastogenesis by antagonizing NF-kappaB activation.
AB  - Strontium ranelate, a pharmaceutical agent shown in clinical trials to be
      effective in managing osteoporosis and reducing fracture risk in postmenopausal
      women, is relatively unique in its ability to both blunt bone resorption and
      stimulate bone formation. However, its mechanisms of action are largely unknown.
      As the nuclear factor-kappa B (NF-kappaB) activation antagonists both stimulate
      osteoblastic bone formation and repress osteoclastic bone resorption, we
      hypothesized that strontium ranelate may achieve its anabolic and anti-catabolic
      activities by modulating NF-kappaB activation in bone cells. In this study,
      osteoclast and osteoblast precursors were treated with intact strontium ranelate
      or its individual components sodium ranelate and/or strontium chloride, and its
      effect on in vitro osteoclastogenesis and osteoblastogenesis and on NF-kappaB
      activation quantified. Although the activity of strontium ranelate has been
      attributed to the release of strontium ions, low dose intact strontium ranelate
      complex, but not sodium ranelate and/or strontium chloride, potently antagonized
      NF-kappaB activation in osteoclasts and osteoblasts in vitro, and promoted
      osteoblast differentiation while suppressing osteoclast formation. Taken
      together, our data suggest a novel centralized mechanism by which strontium
      ranelate promotes osteoblast activity and suppresses osteoclastogenesis, based on
      suppression of NF-kappaB signal transduction. We further demonstrate that the
      biological actions of strontium ranelate may be related to low dose of the intact
      molecule rather than dissociation and release of strontium ions, as previously
      thought. These data may facilitate the development of additional novel
      pharmacological agents for the amelioration of osteoporosis, based on NF-kappaB
      blockade.

PMID- 21874316
TI  - Dietary Guidelines for Americans 2010: implications for cardiovascular disease.
AB  - The 2010 Dietary Guidelines for Americans (DGA) provides science-based advice to
      promote health and reduce risk of major chronic diseases by diet and physical
      activity. The primary emphasis is on food-based recommendations that meet energy
      and nutrient needs. The DGA is made in the context of a total diet designed to
      reduce the incidence and prevalence of overweight and obesity. In addition, the
      DGA also targets cardiovascular disease (CVD) risk reduction. DGA recommends
      nutrient-dense foods including fruits and vegetables, whole grains, low-fat
      dairy, lean protein foods including seafood, and vegetable oils. This dietary
      pattern beneficially affects blood lipids and other CVD risk factors. Foods and
      nutrients to limit include solid fats (saturated fatty acids, trans-fatty acids),
      dietary cholesterol, added sugars, refined grains, and sodium. Healthy dietary
      patterns that emphasize nutrient-dense foods will significantly benefit public
      health, in part, by reducing CVD risk.

PMID- 21874317
TI  - An all-oral combination of metronomic cyclophosphamide plus capecitabine in
      patients with anthracycline- and taxane-pretreated metastatic breast cancer: a
      phase II study.
AB  - PURPOSE: Oral administration of cyclophosphamide (CTX) and capecitabine may have
      a greater potential for treatment of metastatic breast cancer (MBC) due to anti
      angiogenesis resulting from the metronomic dosage and upregulation of thymidine
      phosphorylase by CTX. The purpose of this phase II study was to evaluate the
      efficacy and safety profile of an all-oral combination of metronomic CTX plus
      capecitabine for women with anthracycline- and taxane-pretreated MBC. METHOD: In
      this prospective single-center, open-label, phase II trial, patients with
      measurable disease received oral metronomic CTX 65 mg/m(2) daily on days 1-14
      plus capecitabine 1,000 mg/m(2) twice daily on days 1-14. The treatment was
      repeated every 3 weeks, and continued until disease progression, unacceptable
      toxicity or withdrawal of informed consent. The primary endpoint of the study was
      time to progression (TTP). RESULTS: A total of 68 patients were enrolled and
      received 537 cycles of chemotherapy with a median of 8 cycles (range: 1-30
      cycles) per patient. Sixty-six patients were evaluated for efficacy with all
      patients for toxicity. With a median follow-up time of 26 months, the median time
      to progression was 5.2 months (95% CI, 4.2-6.2 months), and the median overall
      survival was 16.9 months. The overall response rate was 30.3% (95% CI, 20-43%).
      Clinical benefit rate was 53.0% (95% CI, 38-62%). The doublet was well tolerable,
      with anorexia (7.5%), the only grade 3/4 adverse events occurring in more than 5%
      of patients. Grade 3 hand-foot syndrome was 4.4%. CONCLUSION: The all-oral
      combination of metronomic CTX plus capecitabine is an effective and convenient
      and well-tolerated regimen for MBC. (ClinicalTrials.gov number, NCT00589901).

PMID- 21874318
TI  - Phase I dose escalation study of KOS-1584, a novel epothilone, in patients with
      advanced solid tumors.
AB  - PURPOSE: First-in-man study of KOS-1584, a second generation epothilone. METHODS:
      Patients with advanced solid malignancies received KOS-1584 every 3 weeks until
      disease progression. Using a modified Fibonacci dose escalation scheme, one
      patient was enrolled at each dose level until the first instance of grade 2
      toxicity. Thereafter, a standard 3 + 3 design was utilized. RESULTS: Sixty-six
      patients in 14 cohorts were dosed from 0.8 to 48 mg/m(2). Diarrhea, arthralgias,
      and encephalopathy were dose-limiting toxicities (DLTs) at doses >=36 mg/m(2). At
      the recommended phase II dose (RP2D), the most common adverse effects were
      peripheral neuropathy (low grade), fatigue, arthralgias/myalgias, and diarrhea
      (31, 6%). The incidence of neutropenia was low. The overall clearance, volume of
      distribution, and half-life of KOS-1584 were 11 +/- 6.17 L/h/m(2), 327 +/- 161
      L/m(2), and 21.9 +/- 8.75 h, respectively. The half-life for the seco-metabolite
      (KOS-1891) was 29.6 +/- 13.8 h. KOS-1584 exhibited linear pharmacokinetics. A
      dose-dependent increase in microtubulin bundle formation was observed at doses
      >=27 mg/m(2). Two patients achieved partial responses and 24 patients had stable
      disease (SD). CONCLUSIONS: The RP2D of KOS-1584 is 36 mg/m(2). The lack of severe
      neurologic toxicity, diarrhea, neutropenia, or hypersensitivity reactions;
      favorable pharmacokinetic profile; and early evidence of activity support further
      evaluation.

PMID- 21874319
TI  - A mathematical model of calcium and phosphorus metabolism in two forms of
      hyperparathyroidism.
AB  - Parathyroid hormone (PTH) plays a critical role in calcium and phosphorus
      metabolism. Interestingly, in two forms of hyperparathyroidism (excessive amount
      of PTH in the serum), the metabolic disturbances in patients with chronic kidney
      disease (CKD) significantly differ from those with primary hyperparathyroidism
      (PHP). Since an intuitive understanding of these PTH-linked regulatory mechanisms
      are hardly possible, we developed a mathematical model using clinical data (1586
      CKD and 40 PHP patients). The model was composed of a set of ordinary
      differential equations, in which the regulatory mechanism of PTH together with
      other key factors such as 1,25-Dihydroxyvitamin D (1,25(OH)2D) and calcium was
      described in the tissues including bone, the kidney, the serum, and the
      parathyroid glands. In this model, an increase in PTH was induced by its
      autonomous production in PHP, while PTH in CKD was elevated by a decrease in
      feedback inhibition of 1,25(OH)2D in the serum, as well as an increase in
      stimulation by phosphorus in the serum. The model-based analysis revealed
      characteristic differences in the outcomes of hyperparathyroidism in CKD and PHP.
      The calcium exchange in bone, for instance, was predicted significantly higher in
      PHP than CKD. Furthermore, we evaluated the observed and predicted responses to
      the administration of calcimimetics, a recently developed synthetic drug that
      modulated efficacy of calcium-sensing receptors. The results herein support the
      notion that the described model would enable us to pose testable hypotheses about
      the actions of PTH, providing a quantitative analytical tool for evaluating
      treatment strategies of PHP and CKD.

PMID- 21874320
TI  - Ghrelin reduces voltage-gated calcium currents in GH3 cells via cyclic GMP
      pathways.
AB  - Ghrelin is an endogenous growth hormone secretagogue (GHS) causing release of GH
      from pituitary somatotropes through the GHS receptor. Secretion of GH is linked
      directly to intracellular free Ca2+ concentration ([Ca2+]i), which is determined
      by Ca2+ influx and release from intracellular Ca2+ storage sites. Ca2+ influx is
      via voltage-gated Ca2+ channels, which are activated by cell depolarization. The
      mechanism underlying the effect of ghrelin on voltage-gated Ca2+ channels is
      still not clear. In this report, using whole cell patch-clamp recordings, we
      assessed the acute action of ghrelin on voltage-activated Ca2+ currents in GH3
      rat somatotrope cell line. Ca2+ currents were divided into three types (T, N, and
      L) through two different holding potentials (-80 and -40 mV) and specific L-type
      channel blocker (nifedipine, NFD). We demonstrated that ghrelin significantly and
      reversibly decreases all three types of Ca2+ currents in GH3 cells through GHS
      receptors on the cell membrane and down-stream signaling systems. With different
      signal pathway inhibitors, we observed that ghrelin-induced reduction in voltage
      gated Ca2+ currents in GH3 cells was mediated by a protein kinase G-dependent
      pathways. As ghrelin also stimulates Ca2+ release and prolongs the membrane
      depolarization, this reduction in voltage-gated Ca2+ currents may not be
      translated into a reduction in [Ca2+]i, or a decrease in GH secretion.

PMID- 21874321
TI  - The importance of correction for tissue fraction effects in lung PET: preliminary
      findings.
AB  - PURPOSE: It has recently been recognized that PET/CT may play a role in diffuse
      parenchymal lung disease. However, interpretation can be confounded due to the
      variability in lung density both within and between individuals. To address this
      issue a novel correction method is proposed. METHODS: A CT scan acquired during
      shallow breathing is registered to a PET study and smoothed so as to match the
      PET resolution. This is used to derive voxel-based tissue fraction correction
      factors for the individual. The method was evaluated in a lung phantom study in
      which the lung was simulated by a Styrofoam/water mixture. The method was further
      evaluated using (18)F-FDG in 12 subjects free from pulmonary disease where ranges
      before and after correction were considered. RESULTS: Correction resulted in
      similar activity concentrations for the lung and background regions, consistent
      with the experimental phantom set-up. Correction resulted in reduced inter- and
      intrasubject variability in the estimated SUV. The possible application of the
      method was further demonstrated in five subjects with interstitial lung changes
      where increased SUV was demonstrated. Single study pre- and post-treatment
      studies were also analysed to further illustrate the utility of the method.
      CONCLUSION: The proposed tissue fraction correction method is a promising
      technique to account for variability of density in interpreting lung PET studies.

PMID- 21874322
TI  - Statistical parametric maps of 18F-FDG PET and 3-D autoradiography in the rat
      brain: a cross-validation study.
AB  - PURPOSE: Although specific positron emission tomography (PET) scanners have been
      developed for small animals, spatial resolution remains one of the most critical
      technical limitations, particularly in the evaluation of the rodent brain. The
      purpose of the present study was to examine the reliability of voxel-based
      statistical analysis (Statistical Parametric Mapping, SPM) applied to (18)F
      fluorodeoxyglucose (FDG) PET images of the rat brain, acquired on a small animal
      PET not specifically designed for rodents. The gold standard for the validation
      of the PET results was the autoradiography of the same animals acquired under the
      same physiological conditions, reconstructed as a 3-D volume and analysed using
      SPM. METHODS: Eleven rats were studied under two different conditions: conscious
      or under inhalatory anaesthesia during (18)F-FDG uptake. All animals were studied
      in vivo under both conditions in a dedicated small animal Philips MOSAIC PET
      scanner and magnetic resonance images were obtained for subsequent spatial
      processing. Then, rats were randomly assigned to a conscious or anaesthetized
      group for postmortem autoradiography, and slices from each animal were aligned
      and stacked to create a 3-D autoradiographic volume. Finally, differences in
      (18)F-FDG uptake between conscious and anaesthetized states were assessed from
      PET and autoradiography data by SPM analysis and results were compared. RESULTS:
      SPM results of PET and 3-D autoradiography are in good agreement and led to the
      detection of consistent cortical differences between the conscious and
      anaesthetized groups, particularly in the bilateral somatosensory cortices.
      However, SPM analysis of 3-D autoradiography also highlighted differences in the
      thalamus that were not detected with PET. CONCLUSION: This study demonstrates
      that any difference detected with SPM analysis of MOSAIC PET images of rat brain
      is detected also by the gold standard autoradiographic technique, confirming that
      this methodology provides reliable results, although partial volume effects might
      make it difficult to detect slight differences in small regions.

PMID- 21874323
TI  - Differential diagnosis of solitary pulmonary nodules using 99mTc-3P4-RGD2
      scintigraphy.
AB  - PURPOSE: Targeting of integrin alpha(nu)beta(3) with molecular imaging agents
      offers great potential in early detection and monitoring of tumour angiogenesis.
      Recently, an RGD (Arg-Gly-Asp) tracer, (99m)Tc-3P(4)-RGD(2), with high affinity
      to integrin alpha(nu)beta(3) and in vivo tumour uptake was developed. In this
      study, we evaluate the feasibility of this novel radiotracer in the noninvasive
      differentiation of solitary pulmonary nodules (SPNs). METHODS: Twenty-one
      patients with SPNs on CT were studied scintigraphically after administration of
      (99m)Tc-3P(4)-RGD(2) with a dose of 939 +/-  118 MBq. Image interpretation using
      a 5-point scale was performed by one thoracic radiologist for CT and three
      nuclear medicine radiologists for single photon emission computed tomography
      (SPECT). Scintigraphic images were also analysed semiquantitatively by
      calculating tumour to normal tissue ratio (T/N). The "gold standard" was based on
      the histopathological diagnosis of the surgical samples from all recruited
      patients. A fraction of the samples were analysed immunohistochemically for
      integrin alpha(v)beta(3) expression. RESULTS: Among the 21 SPNs, 15 (71%) were
      diagnosed as malignant and 6 (29%) were benign. The mean size for SPNs was 2.2 +/
      0.6 cm. The sensitivity and specificity for CT interpretation, SPECT visual and
      semiquantitative analysis were 80/67%, 100/67% and 100/67%, respectively. All
      SPNs classified as indeterminate by CT were correctly diagnosed by (99m)Tc-3P(4)
      RGD(2) scintigraphy. The empirical receiver-operating characteristic (ROC) areas
      were 0.811 [95% confidence interval (CI) 58-95%] for CT, 0.833 (95% CI 61-96%)
      for SPECT and 0.844 (95% CI 62-96%) for T/N ratios, respectively.
      Immunohistochemistry confirmed alpha(nu)beta(3) expression in malignant and
      benign nodules with uptake in (99m)Tc-3P(4)-RGD(2) scintigraphy. CONCLUSION: In
      this first-in-human study, we demonstrated the feasibility of using (99m)Tc-3P(4)
      RGD(2) scintigraphy in differentiating SPNs. This procedure appears to be highly
      sensitive in detection of malignant SPNs. SPECT visual analysis seems to be
      sufficient for characterization of SPNs.

PMID- 21874324
TI  - Attenuation correction for myocardial perfusion SPECT imaging: still a
      controversial issue.

PMID- 21874325
TI  - Prognostic value of proliferating cell nuclear antigen in parotid gland cancer.
AB  - Although cell proliferation is related to tumour aggressiveness and prognosis,
      there are few studies describing the expression of proliferative markers in
      salivary gland cancer. Our aim was to assess the long-term prognostic value of
      the proliferating cell nuclear antigen (PCNA) in a large group of histologically
      different salivary gland cancers. We analysed the expression of PCNA in 159
      patients with parotid gland cancer by means of immunohistochemistry. The mean
      follow-up time was 56.6 months. A high expression of PCNA showed a significant
      correlation to the patients' pathological lymph node stage (p = 0.004). A high
      PCNA expression significantly indicated a poor 5-year disease-free (p = 0.046)
      and overall survival rate (p = 0.018). The PCNA expression was the only
      prognostic factor for a worse 5-year disease-free and overall survival in acinic
      cell carcinomas (p = 0.004, p = 0.022). The correlation between PCNA expression
      and survival probabilities of salivary gland cancer might make proliferation
      markers helpful tools in patient follow-up, prognosis and targeted therapy in
      salivary gland cancer in future.

PMID- 21874326
TI  - Tenascin-C fragments are endogenous inducers of cartilage matrix degradation.
AB  - Cartilage destruction is a hallmark of osteoarthritis (OA) and is characterized
      by increased protease activity resulting in the degradation of critical
      extracellular matrix (ECM) proteins essential for maintaining cartilage
      integrity. Tenascin-C (TN-C) is an ECM glycoprotein, and its expression is
      upregulated in OA cartilage. We aimed to investigate the presence of TN-C
      fragments in arthritic cartilage and establish whether they promote cartilage
      degradation. Expression of TN-C and its fragments was evaluated in cartilage from
      subjects undergoing joint replacement surgery for OA and RA compared with normal
      subjects by western blotting. The localization of TN-C in arthritic cartilage was
      also established by immunohistochemistry. Recombinant TN-C fragments were then
      tested to evaluate which regions of TN-C are responsible for cartilage-degrading
      activity in an ex vivo cartilage explant assay measuring glycosaminoglycan (GAG)
      release, aggrecanase and matrix metalloproteinase (MMP) activity. We found that
      specific TN-C fragments are highly upregulated in arthritic cartilage.
      Recombinant TN-C fragments containing the same regions as those identified from
      OA cartilage mediate cartilage degradation by the induction of aggrecanase
      activity. TN-C fragments mapping to the EGF-L and FN type III domains 3-8 of TN-C
      had the highest levels of aggrecan-degrading ability that was not observed either
      with full-length TN-C or with other domains of TN-C. TN-C fragments represent a
      novel mechanism for cartilage degradation in arthritis and may present new
      therapeutic targets for the inhibition of cartilage degradation.

PMID- 21874329
TI  - Caffeine, dopamine and thermoregulation.

PMID- 21874328
TI  - Age-related loss of calcium buffering and selective neuronal vulnerability in
      Alzheimer's disease.
AB  - The reasons for the selective vulnerability of distinct neuronal populations in
      neurodegenerative disorders are unknown. The cholinergic neurons of the basal
      forebrain are vulnerable to pathology and loss early in Alzheimer's disease and
      in a number of other neurodegenerative disorders of the elderly. In the primate,
      including man, these neurons are rich in the calcium buffer calbindin-D(28K).
      Here, we confirm that these neurons undergo a substantial loss of calbindin in
      the course of normal aging and report a further loss of calbindin in Alzheimer's
      disease both at the level of RNA and protein. Significantly, cholinergic neurons
      that had lost their calbindin in the course of normal aging were those that
      selectively degenerated in Alzheimer's disease. Furthermore, calbindin-containing
      neurons were virtually resistant to the process of tangle formation, a hallmark
      of the disease. We conclude that the loss of calcium buffering capacity in these
      neurons and the resultant pathological increase in intracellular calcium are
      permissive to tangle formation and degeneration.

PMID- 21874330
TI  - Influence of extra virgin olive oil diet enriched with hydroxytyrosol in a
      chronic DSS colitis model.
AB  - PURPOSE: Recent epidemiological studies have shown that habitual consumption of
      extra virgin olive oil (EVOO), the characteristic culinary fat of the
      Mediterranean area, is effective in the prevention of diverse types of digestive
      disorders such as inflammatory bowel disease. Many of these benefits are, in
      addition to its high proportion of oleic acid, due to the high content of
      phenolic compounds. METHODS: Six-week-old mice were randomized into three dietary
      groups: standard, EVOO and hydroxytyrosol-enriched EVOO. After 30 days, mice that
      were exposed to 3% DSS for 5 days developed acute colitis that progressed to
      severe chronic inflammation during a regime of 21 days of water. RESULTS: Diets
      enriched with EVOO significantly attenuated the clinical and histological signs
      of damage, improving results from disease activity index and reducing about 50%
      the mortality caused by DSS. Moreover, hydroxytyrosol supplement showed better
      results. Cytokines study showed that TNF-alpha was maintained near to sham
      control and IL-10 levels were significantly improved in EVOO and EVOO plus
      hydroxytyrosol diet-DSS groups. In the same way, COX-2 and iNOS were
      downregulated, and the activation of p38 MAPK was reduced. We also observed a
      higher significant reduction in iNOS in hydroxytyrosol-enriched EVOO compared
      with EVOO alone. CONCLUSIONS: EVOO diets exerted a noteworthy beneficial effect
      in chronic DSS-induced colitis by cytokine modulation and COX-2 and iNOS
      reduction via downregulation of p38 MAPK. In addition to the beneficial effect by
      EVOO, supplementation of the diet with hydroxytyrosol may improve chronic colitis
      through iNOS downregulation plus its antioxidant capacity.

PMID- 21874331
TI  - Prenatal exposure to beta2-adrenergic receptor agonists and risk of autism
      spectrum disorders.
AB  - This study aims to investigate the association between prenatal exposure to
      terbutaline and other beta2 adrenergic receptor (B2AR) agonists and autism
      spectrum disorders (ASDs). The methodology used is a case-control study among
      children born from 1995 to 1999 at Kaiser Permanente Northern California
      hospitals. Cases (n = 291) were children with an ASD diagnosis; controls (n =
      284) were children without ASDs, randomly sampled and frequency-matched to cases
      on sex, birth year, and delivery hospital. Exposure to B2AR agonists during 30
      days prior to conception and each trimester of pregnancy was ascertained from
      prenatal medical records and health plan databases. The frequency of exposure to
      any B2AR agonist during pregnancy was similar for mothers of children with ASD
      and mothers of controls (18.9% vs. 14.8%, P = 0.19). Exposure to B2AR agonists
      other than terbutaline was not associated with an increased risk for ASDs.
      However, terbutaline exposure for >2 days during the third trimester was
      associated with more than a fourfold increased risk for ASDs independent of
      indication although the limited sample size resulted in an imprecise and
      nonsignificant effect estimate (OR(adj) = 4.4; 95% confidence interval, 0.8
      24.6). This analysis does not offer evidence linking B2AR exposure in pregnancy
      with autism risk. However, exposure to terbutaline during the third trimester for
      >2 days may be associated with an increased risk of autism. Should this result be
      confirmed in larger samples, it would point to late pregnancy as an etiologic
      window of interest in autism risk factor research.

PMID- 21874332
TI  - A primer for data assimilation with ecological models using Markov Chain Monte
      Carlo (MCMC).
AB  - Data assimilation, or the fusion of a mathematical model with ecological data, is
      rapidly expanding knowledge of ecological systems across multiple spatial and
      temporal scales. As the amount of ecological data available to a broader audience
      increases, quantitative proficiency with data assimilation tools and techniques
      will be an essential skill for ecological analysis in this data-rich era. We
      provide a data assimilation primer for the novice user by (1) reviewing data
      assimilation terminology and methodology, (2) showcasing a variety of data
      assimilation studies across the ecological, environmental, and atmospheric
      sciences with the aim of gaining an understanding of potential applications of
      data assimilation, and (3) applying data assimilation in specific ecological
      examples to determine the components of net ecosystem carbon uptake in a forest
      and also the population dynamics of the mayfly (Hexagenia limbata, Serville). The
      review and examples are then used to provide guiding principles to newly
      proficient data assimilation practitioners.

PMID- 21874334
TI  - Is radiology a determinant of pain, stiffness, and functional disability in knee
      osteoarthritis? A cross-sectional study.
AB  - BACKGROUND AND PURPOSES: Discordance between clinical and radiological profiles
      in knee osteoarthritis has been reported. We hypothesized that the discordance
      could be due to limited radiological variables studied. This study essentially
      analyzed many more radiological features than previous studies in order to seek
      an association between clinical and radiographic features. METHODS: One hundred
      and eighty patients with knee osteoarthritis were enrolled as per the American
      College of Rheumatology (ACR) guidelines. Visual analog scale (VAS) for knee pain
      and the knee-specific Western Ontario Mac University (WOMAC) index for pain,
      stiffness, and disability were recorded. Five additional radiological features
      apart from those in the Kellgren-Lawrence (KL) classification grading system were
      recorded by two authors who were blinded to the clinical diagnosis. The variables
      significantly associated were analyzed by linear regression model. RESULTS: Pain
      was significantly associated with increasing KL grades; physical function was
      nearly significant and stiffness was not. On analysis of individual radiological
      features, WOMAC pain was significant with subchondral sclerosis, joint space
      width, and tibiofemoral alignment although the correlation was week. VAS pain was
      significant with the latter two and with articular incongruity. Functional
      disability was associated with medial joint-space narrowing, tibiofemoral
      alignment, loose bodies, and juxta-articular osteopenia. However, in the linear
      regression model, pain and stiffness were significantly associated with articular
      incongruity and functional disability and total clinical scores with juxta
      articular osteopenia. CONCLUSION: When the radiological features were extended
      beyond those included in KL grades, pain, stiffness, and disability correlated
      well with radiography; articular incongruity with pain and stiffness; and juxta
      articular osteopenia with physical disability and clinical severity.

PMID- 21874333
TI  - Closure of multiple types of K+ channels is necessary to induce changes in renal
      vascular resistance in vivo in rats.
AB  - Inhibition of K(+) channels might mediate renal vasoconstriction. As inhibition
      of a single type of K(+) channel caused minor or no renal vasoconstriction in
      vivo in rats, we hypothesized that several classes of K(+) channels must be
      blocked to elicit renal vasoconstriction. We measured renal blood flow (RBF) in
      vivo in anesthetized Sprague-Dawley rats. Test agents were infused directly into
      the renal artery to avoid systemic effects. Inhibition of BK(Ca) and K(ir)
      channels (with TEA and Ba(2+), respectively) caused small and transient
      reductions in RBF (to 93 +/- 2% and 95 +/- 1% of baseline, respectively). K(ATP),
      SK(Ca) or K(v) channel blockade (with glibenclamide, apamin and 4-aminopyridine,
      respectively) was without effect. However, a cocktail of all blockers caused a
      massive reduction of RBF (to 15 +/- 10% of baseline). Nifedipine and mibefradil
      abolished and reduced, respectively, this RBF reduction. The effect of the
      cocktail of K(+) channel blockers was confirmed in mice using the isolated blood
      perfused juxtamedullary nephron preparation. A cocktail of K(+) channel openers
      (K(+), NS309, NS1619 and pinacidil) had only a minor effect on baseline RBF in
      vivo in rats, but reduced the vasoconstriction induced by bolus injections of
      norepinephrine or angiotensin II (by 33 +/- 5% and 60 +/- 5%, respectively). Our
      results indicate that closure of numerous types of K(+) channels could
      participate in the mediation of agonist-induced renal vasoconstriction. Our
      results also suggest that renal vasoconstriction elicited by K(+) channel
      blockade is mediated by nifedipine-sensitive Ca(2+) channels and partly by
      mibefradil-sensitive Ca(2+) channels.

PMID- 21874335
TI  - Risk of postoperative complications in rheumatoid arthritis relevant to treatment
      with biologic agents: a report from the Committee on Arthritis of the Japanese
      Orthopaedic Association.
AB  - PURPOSE: Since biologic agents were introduced to treat rheumatoid arthritis (RA)
      in 2003, the number of orthopedic surgical procedures under treatment with
      biologic agents has been increasing in Japan. However, whether biologic agents
      cause an increase in the prevalence of postoperative complications is as yet
      unknown. The Committee on Arthritis of the Japanese Orthopedic Association
      investigated the prevalence of postoperative complications in patients with RA in
      teaching hospitals in Japan. METHODS: Between January 2004 and November 2008,
      surveillance forms about medications and surgical procedures in patients with RA
      were sent to 2,019 teaching hospitals. Data were analyzed by the Rheumatoid
      Arthritis Committee. RESULTS: Biologic agents were administered to RA patients in
      632 of 1,245 hospitals (50.8%); 430 of the 1,245 hospitals (34.5%) used surgical
      intervention under treatment with biologic agents. The number of surgical
      procedures under treatment with biologic agents was 3,468, and the prevalence of
      infection was 1.3% (46 cases). The prevalence of infection was 1.0% (567
      procedures) in 56,339 procedures under treatment with nonbiologic disease
      modifying anti-rheumatic drugs. There were no significant differences between
      biological and nonbiological treatment groups with respect to the prevalence of
      infection. In the joint arthroplasty group, the number of procedures under
      biological and nonbiological treatment was 1,626 and 29,903, and the prevalence
      of infection was 2.1% (34 procedures) and 1.0% (298 procedures), respectively.
      There was a significant difference between groups. The odds ratio was 2.12 (95%
      confidence interval 1.48-3.03, P < 0.0001). CONCLUSION: The chance of having
      biological treatment with joint arthroplasty was more than twofold greater in
      patients with surgical-site infections compared with those treated with
      nonbiologic agents. Caution is required for surgical procedure, perioperative
      course, and obtaining consent for joint arthroplasty for patients with RA
      undergoing surgery under biological agents.

PMID- 21874336
TI  - The effects of arachidonic acid on the endocrine and osmoregulatory response of
      tilapia (Oreochromis mossambicus) acclimated to seawater and subjected to
      confinement stress.
AB  - In previous studies in freshwater tilapia (Oreochromis mossambicus), dietary
      supplementation with arachidonic acid (ArA; 20:4n - 6) had considerable, opposing
      effects on the main ion-transporting enzyme Na(+)/K(+)-ATPase in gills and
      kidneys and changed the release of osmoregulatory hormones, such as cortisol. The
      present study was performed to assess the influence of dietary ArA on (1) the
      osmoregulatory capacity of tilapia acclimated to seawater (SW) (340/00) and (2)
      the osmoregulatory imbalance associated with acute stress. The increased ambient
      salinity was associated with significant alterations in the tissue fatty acid
      composition, particularly the n - 6 polyunsaturated fatty acids (PUFAs). Tissue
      levels of ArA were further increased as a result of dietary supplementation,
      whereas docosahexaenoic acid (DHA, 22:6n - 3) and eicosapentaenoic acid (EPA,
      20:5n - 3) decreased in gills and kidneys. Basal plasma cortisol as well as
      lactate levels were elevated in the ArA-supplemented SW-acclimated tilapia
      compared with the control group. The 5 min of confinement (transient stress)
      increased plasma cortisol, glucose, and lactate levels with significantly higher
      levels in ArA-supplemented tilapia. Confinement was also associated with
      significantly elevated plasma osmolality, sodium, chloride, and potassium levels.
      ArA-supplemented tilapia showed markedly lower ionic disturbances after
      confinement, suggesting that dietary ArA can attenuate the hydromineral imbalance
      associated with acute stress. These results emphasize the involvement of ArA
      and/or its metabolites in the endocrine and osmoregulatory processes and the
      response to confinement stress.

PMID- 21874337
TI  - A qualitative framework to assess hospital / medical websites.
AB  - Nowadays, there are many peoples who access to the internet to search for a
      proper hospital with their desired medical services. Hence, the website quality
      of hospitals or medical centers is very important to help patients/users.
      However, to design high qualitative medical websites, we should first know the
      medical quality metrics. Then, we should try to find a way to assess different
      medical websites based on the quality metrics. In fact, medical websites may have
      a significant role to increase the society's knowledge about people health,
      provided services for patients etc. Thus, it is necessary to design a framework
      to evaluate the quality of these websites. Even though there are many medical
      websites, unfortunately, there are a few studies about quality analysis of
      medical/hospital websites. In this paper, we propose a qualitative framework to
      assess different medical websites. The proposed framework consists of 7 main
      categories, each having different metrics. Finally, to show how these metrics can
      help designers to assess the websites quality, we have considered 3 different
      hospitals as case studies. We asked different people including doctors, website
      designers, and usual peoples to evaluate our defined metrics on each case study.
      At the end, the results are shown through different charts.

PMID- 21874338
TI  - A secure lightweight RFID binding proof protocol for medication errors and
      patient safety.
AB  - Quite recently, Yu et al. presented a real lightweight binding proof protocol to
      guard patient safety and prevent medication errors. In this paper, we first show
      their protocol is still vulnerable to impersonation attacks. Thereafter we
      propose a new lightweight binding proof protocol to overcome these weaknesses and
      securely achieve the goal of proving that two tags exist in the field
      simultaneously.

PMID- 21874339
TI  - Case report of a cervical intraspinal misplacement of a central venous line.
AB  - A case of cervical spinal misplacement of a central venous line via the right
      jugular vein is reported. A review of the literature resulted in eight similar
      cases. Only two further adults are described. Children and patients suffering
      from malnutrition seem to have a higher risk for intraspinal malpositioning of
      central venous catheters.

PMID- 21874340
TI  - Improved dimensionally-reduced visual cortical network using stochastic noise
      modeling.
AB  - In this paper, we extend our framework for constructing low-dimensional dynamical
      system models of large-scale neuronal networks of mammalian primary visual
      cortex. Our dimensional reduction procedure consists of performing a suitable
      linear change of variables and then systematically truncating the new set of
      equations. The extended framework includes modeling the effect of neglected modes
      as a stochastic process. By parametrizing and including stochasticity in one of
      two ways we show that we can improve the systems-level characterization of our
      dimensionally reduced neuronal network model. We examined orientation selectivity
      maps calculated from the firing rate distribution of large-scale simulations and
      stochastic dimensionally reduced models and found that by using stochastic
      processes to model the neglected modes, we were able to better reproduce the mean
      and variance of firing rates in the original large-scale simulations while still
      accurately predicting the orientation preference distribution.

PMID- 21874341
TI  - Improving the quality of research into the health of migrant and ethnic groups.

PMID- 21874342
TI  - Effect of factors on decolorization of azo dye methyl orange by oxone/natural
      sunlight in aqueous solution.
AB  - PURPOSE: The oxone process for azo dye decolorization has drawbacks such as
      difficulties with reuse, risks of secondary pollution, and high costs associated
      with UV irradiation. This study aims to explore the use of oxone for
      decolorization in the absence of catalyst and under natural sunlight conditions
      (i.e., oxone/natural sunlight system) and evaluate the impacts of operating
      parameters (reagent dosage, initial methyl orange (MO) concentration, and initial
      pH) and coexisting substances (humic acid, NO(3)(-), metal ions) on the system's
      decolorization efficiency. METHODS: Four levels of operating parameters were
      configured under a Taguchi L(16) orthogonal array design to examine their effects
      on decolorization efficiency. Fractional factional design was then used to derive
      the optimal combination of operating parameters, under which the effects of
      coexisting substances at various concentrations were examined. In addition,
      H(2)O(2), CH(3)OH, and (CH(3))(3)COH were used to derive the possible reaction
      mechanisms in the oxone/sunlight system, while ultrasonic power was used to
      shorten the reaction time. RESULTS: In the oxone/sunlight system, (1) the MO
      decolorization efficiency reaches 96.4% under the optimal operating conditions:
      initial concentration, 100 mg L(-1); initial pH 6.04; dosage of reagent, 3 mmol
      L(-1); and reaction time, 30 min. (2) Coexisting substances do not affect the
      overall decolorization efficiency. (3) The decolorization of MO in the
      oxone/sunlight system takes place mainly via oxidation by SO(4).-. (4) Ultrasonic
      irradiation could remarkably accelerate the MO decolorization process.
      CONCLUSION: Effective for MO decolorization, the oxone/sunlight system improves
      over the traditional oxone process with advantages of lower costs and avoiding
      secondary pollution by catalyst.

PMID- 21874343
TI  - Development of a surgical approach for a wide-view suprachoroidal retinal
      prosthesis: evaluation of implantation trauma.
AB  - BACKGROUND: Our research goal is to develop a safe, reproducible surgical
      approach for implantation of a wide-field retinal stimulating array. The aim of
      this study was to evaluate the pathological response to acute implantation of a
      functional prototype electrode array in the suprachoroidal space. METHODS: The
      surgical techniques to implant a 72 platinum electrode array fabricated on 8 * 13
      * 0.4 mm polyimide and silicone substrate were developed in a pilot study in
      anesthetized cats. For the main study, nine eyes were implanted in vivo and
      unoperated eyes were used as controls. Surgery consisted of a temporal approach
      with a full-thickness scleral incision 5 mm posterior to the limbus. A
      suprachoroidal "pocket" was created, the electrode array inserted to sit beneath
      the area centralis, and placement was confirmed visually. The eyes were collected
      subsequently for histopathology. RESULTS: The array was consistently inserted
      into the suprachoroidal space beneath the area centralis in nine eyes. There was
      a significant hemorrhage in two cases where implantation was complicated by
      choroidal congestion. Retinal folding occurred only when the array tip was within
      2.6 mm of the optic disc (p < 0.01). There was choroidal incarceration at the
      incision in six eyes and scleral distortion at the array edges in five. No cases
      were found where the implant breached the retina, choroid, or sclera.
      CONCLUSIONS: A large stimulation array can be reliably inserted into the
      suprachoroidal space without trauma to the neuroretina. These findings suggest
      that this is an appropriate surgical approach for the placement of an electrode
      array for use in retinal stimulation.

PMID- 21874344
TI  - Microperimetry as a routine diagnostic test in the follow-up of retinal vein
      occlusion?
AB  - BACKGROUND: In the follow-up of retinal vein occlusions, a patient's subjective
      change in vision frequently cannot be confirmed by objective measurements.
      Furthermore, contradictory results of OCT and distance visual acuity give the
      impression that current routine diagnostic tests might not be satisfying for
      patients with retinal vein occlusions. This prospective case series analyses the
      value of microperimetry as a routine diagnostic test in the follow-up of patients
      with retinal vein occlusions during therapy. METHODS: In a prospective case
      series, we tested microperimetry as a functional measure in comparison to
      distance visual acuity, reading ability, and OCT, on 13 patients treated for
      central or branch retinal vein occlusions. Treatment consisted of intravitreal
      bevacizumab injections combined with panretinal laser coagulation in cases of
      peripheral ischemia. If macular edema persisted, bevacizumab injection was
      repeated, or instead of this intravitreal triamcinolone or focal laser
      coagulation was applicated. Follow-up ranged from 6-14 months. An interim
      analysis was performed for the 6-month follow-up. RESULTS: In the branch retinal
      vein occlusion group, the average of the retinal thickness measured by OCT was
      502.22 MUm (+/-SD 217.75 MUm) at baseline and changed to 396.38 +/- 154.38 at the
      6-month follow-up (p = 0.121). Mean distance visual acuity stayed similar to the
      study entrance with 0.41 +/- 0.34 at the 6-month follow-up (p = 0.944) Mean
      reading ability improved to 0.51 +/- 0.52 at the 6-month follow-up but was not
      statistically significant (p = 0.435). The mean light sensitivity of
      microperimetry improved from baseline to the 6-month follow-up: the 40-points
      group improved from 8.62 +/- 5.69 dB to 10.98 +/- 5.42 (p = 0.060) and the 8
      points group from 6.27 dB to 9.6 dB (p = 0.07) but missed statistical
      significance. The sector group showed in contrast to this an improvement from
      6.02 +/- 5.71 dB to 9 +/- 6.07 dB (p = 0.025), which was statistically
      significant. Changes in the central vein occlusion group were not statistically
      significant but changes for both groups together showed statistical significance.
      CONCLUSIONS: In the present case series, microperimetry was more convenient to
      detect, even the subtle functional changes during the disease course of branch
      retinal vein occlusions than distance and reading visual acuity. This indicates
      that microperimetry could be a possible valuable tool in the follow-up of branch
      retinal vein occlusions.

PMID- 21874345
TI  - Association between photoreceptor integrity and visual outcome in diabetic
      macular edema.
AB  - PURPOSE: To investigate the correlation between foveal photoreceptor integrity
      and final visual acuity (VA) after treatment of eyes with diabetic macular edema
      (DME), and to determine the visual prognostic factors. METHODS: We
      retrospectively studied 61 eyes of 52 patients with DME who were treated
      successfully with intravitreal triamcinolone injection (IVTA). Using spectral
      domain optical coherence tomography (SD-OCT), the eyes were categorized into
      three groups at the final visit according to restoration of the photoreceptor
      inner and outer segment junction (IS/OS) and the external limiting membrane
      (ELM): (1) the A group, with a completely visible IS/OS and ELM, (2) the B group,
      with a disrupted IS/OS and intact ELM, and (3) the C group, with a disrupted or
      loss of the IS/OS and ELM. Disrupted IS/OS length (DIL), disrupted ELM length
      (DEL), and mean disrupted IS/OS and ELM length (DIEL) were measured at the
      initial and final visits. Foveal thickness (FT), macular center thickness (MCT),
      and outer nuclear layer (ONL) thickness were also measured at the initial and
      final visits. Multivariate analysis testing was performed over the measured SD
      OCT variables. RESULTS: Final VA was closely associated with IS/OS integrity at
      the final visit; final VA (logMAR) in the A group (0.21 +/- 0.14; 31 eyes) or B
      group (0.31 +/- 0.21; 15 eyes) was significantly better than that in the C group
      (0.45 +/- 0.33; 15 eyes) (p < 0.001). Shorter DIL, DEL, and DIEL at the final
      visit were associated with better final VA. Multivariate analysis showed that
      DIEL (r = 0.564) have the greatest correlation coefficient with final VA compared
      to DIL (r = 0.561) and DEL (r = 0.540). Better VA, preservation of the IS/OS and
      ELM at the initial visit were associated with intact photoreceptor integrity
      after resolution of DME. However, MCT, FT, and ONL thickness had no significant
      correlation with photoreceptor integrity. CONCLUSION: IS/OS and ELM are useful
      hallmarks for use in evaluation of foveal photoreceptor layer integrity, and are
      closely associated with final VA in DME. Pretreatment VA and photoreceptor status
      can predict potential restoration of photoreceptor integrity and subsequent
      visual recovery in DME.

PMID- 21874346
TI  - Retinal blood flow velocity measured by retinal function imaging in retinitis
      pigmentosa.
AB  - BACKGROUND: To measure the retinal blood flow velocity in patients with retinitis
      pigmentosa using the retinal function imaging technique. METHODS: The clinical
      observational investigation included a study group of five eyes of five patients
      (age: 55.7 +/- 8.6 years) with retinitis pigmentosa (RP) and a control group of
      five eyes of five healthy subjects. We used a randomly chosen eye of the RP
      patients, and compared its results to the normal subjects using a mixed linear
      model, correcting for heart rate, age, and gender. RESULTS: The mean blood
      velocity in the narrow retinal veins (1.7 +/- 0.35 cm/s versus 3.0 +/- 0.35 cm/s;
      P < 0.001) and wide retinal veins (1.5 +/- 0.35 cm/s versus 3.1 +/- 0.30 cm/s; P
      < 0.001) was significantly lower in the study group than in the control group not
      correcting for heart rate, age or gender. Correspondingly, the arterial blood
      flow velocity was significantly lower in the study group than in the control
      group for the narrow arterial vessels (2.3 +/- 0.55 versus 4.2 +/- 0.5; P =
      0.006) and for the wide retinal arteries (2.5 +/- 1.05 cm/s versus 4.8 +/- 1.0
      cm/s; P < 0.001). CONCLUSIONS: Using the retinal function imaging technology
      revealed significantly lower retinal blood flow velocities in the small and large
      retinal vessels in patients with retinitis pigmentosa than in healthy subjects.
      This corresponds with the known decrease in the retinal vessel diameters as
      observed upon ophthalmoscopy in patients with retinitis pigmentosa. Retinal
      function imaging technology may hold promise for measurements of retinal blood
      flow parameters.

PMID- 21874347
TI  - UVA-riboflavin photochemical therapy of bacterial keratitis: a pilot study.
AB  - BACKGROUND: The aim of this work as to investigate the photochemical interaction
      used in corneal crosslinking (CXL) as the primary therapy for bacterial
      keratitis. METHODS: A prospective non-randomized study was conducted including 16
      patients with a clinical diagnosis of bacterial keratitis. No patient had any
      prior antibiotic treatment for the current infection. Photography and microbial
      culturing of the infected cornea were performed. Riboflavin was topically
      administered for 20 min and ultraviolet light (UVA) exposure settings for
      treatment of keratoconus were used. After the procedure, clinical examinations
      were done at least once daily until signs of improvement had been established.
      The frequency of examinations was thereafter reduced. Antibiotic therapy was
      initiated if infectious progression was suspected. The trial was registered at
      ISCRTN.org (no: 21432643). RESULTS: All eyes responded to the photochemical
      treatment with improvement in symptoms and signs of reduced inflammation.
      Epithelial healing was achieved in all cases. Antibiotic administration was
      necessary in two cases. One patient required a human amniotic membrane
      transplant. CONCLUSIONS: This trial illustrates that photosensitization of
      riboflavin using UVA at 365 nm has the potential to induce healing in patients
      with microbial keratitis. The results from the treatment of these 16 patients
      with corneal ulcers indicate that UVA-riboflavin photochemical therapy merits a
      controlled study in order to assess its efficacy and safety compared to
      antibiotics.

PMID- 21874349
TI  - The PAL2 promoter activities in relation to structural development and adaptation
      in Arabidopsis thaliana.
AB  - Phenylalanine ammonia lyase (PAL) plays a major role in plant growth, development
      and adaptation. In Arabidopsis thaliana, the enzyme is encoded by four genes,
      namely PAL1, PAL2, PAL3, and PAL4 with PAL1 and PAL2 being closely related
      phylogenetically and functionally. PAL1 promoter activities are associated with
      plant development and are inducible by various stress agents. However, PAL2
      promoter activities have not been functionally analysed. Here, we show that the
      PAL2 promoter activities are associated with the structural development of a
      plant and its organs. This function was inducible in an organ-specific manner by
      the avirulent strain of Pseudomonas syringae pv. tomato (JL1065). The PAL2
      promoter was active throughout the course of the plant development particularly
      in the root, rosette leaf, and inflorescence stem that provide the plant with
      structural support. In aerial organs, the levels of PAL2 promoter activities were
      negatively correlated with relative positions of the organs to the rosette
      leaves. The promoter was inducible in the root following an inoculation by JL1065
      in the leaf suggesting PAL2 to be part of an induced defence system. Our results
      demonstrate how the PAL2 promoter activities are being coordinated and
      synchronised for the structural development of the plant and its organs based on
      the developmental programme. Under certain stress conditions the activity may be
      induced in favour of certain organs.

PMID- 21874352
TI  - Respondent-driven sampling and the recruitment of people with small injecting
      networks.
AB  - Respondent-driven sampling (RDS) is a form of chain-referral sampling, similar to
      snowball sampling, which was developed to reach hidden populations such as people
      who inject drugs (PWID). RDS is said to reach members of a hidden population that
      may not be accessible through other sampling methods. However, less attention has
      been paid as to whether there are segments of the population that are more likely
      to be missed by RDS. This study examined the ability of RDS to capture people
      with small injecting networks. A study of PWID, using RDS, was conducted in 2009
      in Sydney, Australia. The size of participants' injecting networks was examined
      by recruitment chain and wave. Participants' injecting network characteristics
      were compared to those of participants from a separate pharmacy-based study. A
      logistic regression analysis was conducted to examine the characteristics
      independently associated with having small injecting networks, using the combined
      RDS and pharmacy-based samples. In comparison with the pharmacy-recruited
      participants, RDS participants were almost 80% less likely to have small
      injecting networks, after adjusting for other variables. RDS participants were
      also more likely to have their injecting networks form a larger proportion of
      those in their social networks, and to have acquaintances as part of their
      injecting networks. Compared to those with larger injecting networks, individuals
      with small injecting networks were equally likely to engage in receptive sharing
      of injecting equipment, but less likely to have had contact with prevention
      services. These findings suggest that those with small injecting networks are an
      important group to recruit, and that RDS is less likely to capture these
      individuals.

PMID- 21874350
TI  - Insights into NK cell biology from human genetics and disease associations.
AB  - Rare human primary immunodeficiency disorders with extreme susceptibility to
      infections in infancy have provided important insights into immune function.
      Increasingly, however, primary immunodeficiencies are also recognized as a cause
      of other more common, often discrete, infectious susceptibilities. In a wider
      context, loss-of-function mutations in immune genes may also cause disorders of
      immune regulation and predispose to cancer. Here, we review the associations
      between human diseases and mutations in genetic elements affecting natural killer
      (NK) cell development and function. Although many such genetic aberrations
      significantly reduce NK cell numbers or severely impair NK cell responses,
      inferences regarding the role of NK cells in disease are confounded by the fact
      that most mutations also affect the development or function of other cell types.
      Still, data suggest an important role for NK cells in diseases ranging from
      classical immunodeficiency syndromes with susceptibility to viruses and other
      intracellular pathogens to cancer, autoimmunity, and hypersensitivity reactions.

PMID- 21874353
TI  - Comparison of human insulin and insulin analogues on hypoglycaemia and metabolic
      variability in type 1 diabetes using standardized measurements (HYPO score and
      Lability Index).
AB  - To evaluate whether treatment with insulin analogues is associated with a lower
      risk of hypoglycaemia (HYPO score) and less glycaemic variability (Lability
      Index) than treatment with human insulin in patients with type 1 diabetes. In a 6
      month prospective, open-labelled trial, we randomized 47 patients treated with
      human insulin to receive treatment with human insulin (n = 21) or insulin
      analogues (n = 26). HYPO score, Lability Index (LI), and hypoglycaemic episode
      characteristics were assessed at baseline and at the end of follow-up. A 72-h,
      continuous glucose monitoring was performed at the end in a subgroup of patients.
      Groups were compared with nonparametric tests. Significance was defined as P <
      0.05. HYPO score (71.5 [36.0-162] vs. 260 [52.0-676], P < 0.05), nocturnal
      hypoglycaemia (0.4 vs. 1.4 events/patient/4-week, P < 0.05), and <2.5 mmol/l
      hypoglycaemic events were lower in insulin analogue group after 6 months. There
      was a trend towards a lower LI in insulin analogue group (74.3 [51.3-133] vs. 123
      [76.4-171] mmol/l(2)/h week(-1), P = 0.064). HbA1c and insulin dose were
      comparable between groups. In type 1 diabetes, insulin analogues were associated
      with a lower hypoglycaemic risk and a trend towards reduced glycaemic variability
      compared with human insulin. These effects occurred despite comparable metabolic
      control.

PMID- 21874351
TI  - Ablation of LMO4 in glutamatergic neurons impairs leptin control of fat
      metabolism.
AB  - The LIM domain only 4 (LMO4) protein is expressed in the hypothalamus, but its
      function there is not known. Using mice with LMO4 ablated in postnatal
      glutamatergic neurons, including most neurons of the paraventricular (PVN) and
      ventromedial (VMH) hypothalamic nuclei where LMO4 is expressed, we asked whether
      LMO4 is required for metabolic homeostasis. LMO4 mutant mice exhibited early
      onset adiposity. These mice had reduced energy expenditure and impaired
      thermogenesis together with reduced sympathetic outflow to adipose tissues. The
      peptide hormone leptin, produced from adipocytes, activates Jak/Stat3 signaling
      at the hypothalamus to control food intake, energy expenditure, and fat
      metabolism. Intracerebroventricular infusion of leptin suppressed feeding
      similarly in LMO4 mutant and control mice. However, leptin-induced fat loss was
      impaired and activation of Stat3 in the VMH was blunted in these mice. Thus, our
      study identifies LMO4 as a novel modulator of leptin function in selective
      hypothalamic nuclei to regulate fat metabolism.

PMID- 21874354
TI  - Anti-arthritic effect of GN1, a novel synthetic analog of glucosamine, in the
      collagen-induced arthritis model in rats.
AB  - OBJECTIVE: Glucosamine is a naturally occurring amino monosaccharide that
      maintains the elasticity and strength of the cartilage tissues. It has been used
      to treat osteoarthritis in humans; however, in severe conditions of inflammation
      and pain, glucosamine alone is not enough, and it is important to improve its
      biological activity. Our research group has recently taken an interest in the
      synthetic manipulation of amino sugars to develop some efficient pharmacophores,
      e.g., beta-D-glucosamine, to combat rheumatoid arthritis, and tested its anti
      arthritic effects in the collagen-induced arthritis (CIA) model in rats. METHODS:
      Arthritis was induced in female Sprague-Dawley rats by multiple intradermal
      injections of bovine type II collagen and challenged again with the same antigen
      preparation 7 days later. Arthritis was evaluated by arthritic score, body weight
      loss, paw volume measurement, and histological changes. RESULTS: The animals in
      the arthritic control group showed a gradual decrease in their body weight and
      concurrent increase in the paw volumes compared to the normal control group. In
      contrast, increased hind paw swelling was significantly suppressed with no
      further noticeable reduction in body weight in the glucosamine (p < 0.05) and GN1
      treated (p < 0.02) arthritic animals. Histopathological evaluation of isolated
      knee joints by grading system and classification of the stages in arthritic
      lesion development revealed suppression of the inflammatory changes in the GN1
      treated animals. Moreover, both the pro-inflammatory markers C-reactive protein
      (CRP) and low-density lipoprotein (LDL) levels were found to be significantly
      decreased in animals treated with GN1 (p < 0.03 for CRP and p < 0.05 for LDL)
      compared to the arthritic control group. CONCLUSION: These results suggest that
      GN1 has both anti-arthritic and anti-inflammatory properties. Its effects in the
      CIA model suggest that it could be useful in the treatment of rheumatoid
      arthritis.

PMID- 21874355
TI  - Role of nitric oxide (NO) metabolism and inflammatory mediators in childhood
      obesity.
AB  - OBJECTIVE AND DESIGN: The role of NO and adipocytokines in childhood obesity was
      studied, supposing that obesity provokes inflammation. Children were admitted to
      the pediatric clinic for a regular check up because of obesity. SUBJECTS: Obese
      (n = 79) and healthy (n = 12) children were selected and divided into subgroups
      according to their age, gender, glucose tolerance and nitric oxide synthase (NOS
      II) positivity. METHODS: Urine and blood nitrite plus nitrate, the expression of
      NOS II in white blood cells, serum adipocytokines and clinical characteristics
      were analyzed in each group. Significance was tested by unpaired two-tailed t
      test and by ANOVA. RESULTS: NOS II was only detected in the white blood cells of
      a subgroup (17/79) of obese children. Serum leptin and resistin concentrations
      were significantly higher, adiponectin was lower compared to healthy children.
      Significant correlations were observed between serum adiponectin and resistin
      levels (reciprocal, R (2) = 0.4), and between body mass index and serum leptin
      levels. CONCLUSIONS: NOS II expression in white blood cells was observed in a
      minority of patients. Low-grade inflammation in obese children was suggested by
      the increased resistin levels, particularly in NOS II-positive patients.
      Correlation between different adipocytokines was restricted for a few subgroups.

PMID- 21874356
TI  - Alteration in inflammatory/apoptotic pathway and histone modifications by
      nordihydroguaiaretic acid prevents acute pancreatitis in swiss albino mice.
AB  - Reactive oxygen radicals, pro-inflammatory mediators and cytokines have been
      implicated in caerulein induced acute pancreatitis. Nordihydroguaiaretic acid
      (NDGA), a plant lignin, has marked anti-inflammatory properties. The present
      study aimed to investigate the possible protective effect of NDGA against
      caerulein induced pancreatitis. Acute pancreatitis was induced by intraperitoneal
      administration of eight doses of caerulein in male swiss albino mice. NDGA was
      administered after 9 h of acute pancreatitis induction. Pancreatic damage and the
      protective effect of NDGA were assessed by oxidative stress parameters and
      histopathology of pancreas. The mRNA expression of heat shock proteins (DNAJ C15
      and HSPD1) was examined by real-time RT-PCR analysis. Expression of HSP 27, NF
      kappaB, TNF-alpha, p-p38, Bcl-2, p-PP2A, procaspase-3, caspase-3 and histone
      modifications were examined by western blotting. NDGA attenuated the oxidative
      stress, led to increased plasma alpha-amylase and decreased IGF-1 in AP mice. It
      modulated the mRNA and protein levels of heat shock proteins and reduced the
      expression of NF-kappaB, TNF-alpha and p-p38. It increased the number of TUNEL
      positive apoptotic cells in the pancreas of AP mice. In addition, NDGA prevented
      the changes in modifications of histone H3 in acute pancreatitis. To best of our
      knowledge, this is the first report which suggests that NDGA prevents the
      progression of acute pancreatitis by involving alteration of histone H3
      modifications and modulating the expression of genes involved in
      inflammatory/apoptotic cascade, which may be responsible for decreased necrosis
      and increased apoptosis in this model of acute pancreatitis.

PMID- 21874357
TI  - Rapamycin protects against dominant negative-HNF1A-induced apoptosis in INS-1
      cells.
AB  - HNF1A-maturity onset diabetes of the young (HNF1A-MODY) is caused by mutations in
      Hnf1a gene encoding the transcription factor hepatocyte nuclear factor 1alpha
      (HNF1A). An increased rate of apoptosis has been associated with the decrease in
      beta-cell mass that is a hallmark of HNF1A-MODY and other forms of diabetes. In a
      cellular model of HNF1A-MODY, we have recently shown that signalling through
      mammalian target of rapamycin (mTOR) is decreased by the overexpression of a
      dominant-negative mutant of HNF1A (DN-HNF1A). mTOR is a protein kinase which has
      important roles in cell metabolism and growth, but also in cell survival, where
      it has been shown to be both protective and detrimental. Here, we show that
      pharmacological inhibition of mTOR activity with rapamycin protected INS-1 cells
      against DN-HNF1A-induced apoptosis. Rapamycin also prevented DN-HNF1A-induced
      activation of AMP-activated protein kinase (AMPK), an intracellular energy sensor
      which we have previously shown to mediate DN-HNF1A-induced apoptosis. Conversely,
      activation of mTOR with leucine potentiated DN-HNF1A-induced apoptosis. Gene
      silencing of raptor (regulatory associated protein of mTOR), a subunit of mTOR
      complex 1 (mTORC1), also conferred protection on INS-1 cells against DN-HNF1A
      induced apoptosis, confirming that mTORC1 mediates the protective effect. The
      potential relevance of this effect with regards to the clinical use of rapamycin
      as an immunosuppressant in diabetics post-transplantation is discussed.

PMID- 21874358
TI  - Acculturation and cross-border utilization of health services.
AB  - Health services from Mexico constitute an important source of care for U.S.
      residents living along the U.S.-Mexico border. Data from The Cross-Border
      Utilization of Health Care Survey (n = 966) were used to estimate logit models
      that related acculturation, as measured by generational status, to the use of
      medication, physician, dental, and inpatient services from Mexico by U.S.
      residents in the Texas border region. Relative to first-generation Mexican
      immigrants, later-generation Mexican-Americans were progressively less likely to
      go to Mexico for health services. This finding holds with or without adjusting
      for the effects of selected demographic and socioeconomic variables. Addressing
      unmet needs in medical care in the southwestern U.S. border area should go beyond
      a simple expansion of health insurance coverage--it is also important to deliver
      health services that are sensitive to generational differences within the
      population in terms of linguistic and cultural barriers to health care access.

PMID- 21874359
TI  - Investigating the myth of the "model minority": a participatory community health
      assessment of Chinese and Vietnamese adults.
AB  - Despite the persistent belief that Asians are the "model minority" there is
      accumulating evidence of health concerns within Asian subgroups. In this study,
      we implemented a cross-sectional participatory community health assessment in an
      urban city in Massachusetts, to understand differences and similarities in
      demographics, health and healthcare access in Chinese and Vietnamese adults. We
      gathered qualitative data from community stakeholders to inform the development
      of a community health assessment tool. The tool elicited information on
      healthcare access, health status, behavioral health and chronic disease history
      and treatment. Healthcare access issues and poor health status, particularly
      among Chinese participants and mental health symptomotology in both groups were
      areas of concern. These findings revealed important health concerns in two Asian
      ethnic groups. Studies are needed to better understand these concerns and inform
      programs and policies to improve health outcomes in these Asian ethnic groups.

PMID- 21874360
TI  - Musculoskeletal imaging with a prototype photon-counting detector.
AB  - OBJECTIVE: To test a digital imaging X-ray device based on the direct capture of
      X-ray photons with pixel detectors, which are coupled with photon-counting
      readout electronics. METHODS: The chip consists of a matrix of 256 * 256 pixels
      with a pixel pitch of 55 MUm. A monolithic image of 11.2 cm * 7 cm was obtained
      by the consecutive displacement approach. Images of embalmed anatomical specimens
      of eight human hands were obtained at four different dose levels (skin dose 2.4,
      6, 12, 25 MUGy) with the new detector, as well as with a flat-panel detector.
      RESULTS: The overall rating scores for the evaluated anatomical regions ranged
      from 5.23 at the lowest dose level, 6.32 at approximately 6 MUGy, 6.70 at 12
      MUGy, to 6.99 at the highest dose level with the photon-counting system. The
      corresponding rating scores for the flat-panel detector were 3.84, 5.39, 6.64,
      and 7.34. When images obtained at the same dose were compared, the new system
      outperformed the conventional DR system at the two lowest dose levels. At the
      higher dose levels, there were no significant differences between the two
      systems. CONCLUSION: The photon-counting detector has great potential to obtain
      musculoskeletal images of excellent quality at very low dose levels.

PMID- 21874361
TI  - Lesion detection at seven Tesla in multiple sclerosis using magnetisation
      prepared 3D-FLAIR and 3D-DIR.
AB  - OBJECTIVES: To examine the feasibility and value of 7 T 3D T2-weighted Fluid
      Attenuated Inversion Recovery (FLAIR) and Double Inversion Recovery (DIR) MR
      sequences for lesion detection in multiple sclerosis (MS). METHODS: High
      resolution 3D-FLAIR and 3D-DIR MR sequences at 7 T were obtained using
      magnetisation preparation (MP), and compared with 2D-T2-weighted and 3D-T1
      weighted sequences in 10 MS patients and five healthy controls. We determined
      contrast ratios and counted lesions according to anatomical location. RESULTS: MR
      imaging at 7 T was safe and allowed multi-contrast imaging within clinically
      acceptable imaging times. Lesion to white matter (WM) and grey matter (GM)
      contrast ratios were higher in 3D-MP-FLAIR and 3D-MP-DIR compared with 2D-T2 and
      3D-T1. Cortical (mixed+intra-cortical) and total lesion counts were 97/592 on 3D
      MP-FLAIR and 100/558 on 3D-MP-DIR compared with 84/384 on 2D-T2 and 42/442 on 3D
      T1. More juxta-cortical lesions were seen with 3D-MP-FLAIR (205) and 3D-MP-DIR
      (133) than with 2D-T2 (125) and 3D-T1 (70). Finally, higher numbers of lesions
      were found for deep WM lesions: 176 for 3D-MP-FLAIR and 196 for 3D-MP-DIR vs. 155
      for 2D-T2 and 131 for 3D-T1. CONCLUSIONS: Near isotropic 3D-MP-FLAIR and 3D-MP
      DIR allows high quality T2-weighted MR imaging in MS at 7 T, improving (cortical)
      lesion detection.

PMID- 21874362
TI  - Maternal overcontrol and child anxiety: the mediating role of perceived
      competence.
AB  - Previous research has shown that maternal overcontrol is related to higher levels
      of child anxiety. It has been theorized, though not empirically tested, that
      maternal overcontrol decreases child perceived competence and mastery, which
      increases child anxiety. The present study investigated this theory using a
      sample of 89 mother-child dyads (children aged 6-13, 84.3% Caucasian, 6.7%
      African American, and 51.7% male). After statistically controlling for maternal
      anxiety level, child perceived competence was shown to partially mediate the
      relationship between maternal overcontrol and child anxiety. Though current
      findings are based on cross sectional data, they suggest multiple pathways
      through which maternal overcontrol impacts child anxiety. One pathway, described
      in theoretical models, posits that greater levels of parental control reduce
      children's opportunities to acquire appropriate developmental skills, lowering
      their perceived competence, and thus increasing their anxiety. Implications of
      these findings and directions for future research are discussed.

PMID- 21874363
TI  - [Diagnosis of malignant bone and soft tissue tumors].
AB  - Primary sarcoma of bone is a rare entity but nevertheless a significant cause of
      mortality in children and adolescents. The focus of the preoperative evaluation
      is to set up a histological diagnosis, define local tumor extent and develop a
      therapy regimen. In addition to patient history and clinical findings a
      radiograph in two orthogonal planes is still of great importance. MRI plays a
      major role in the further clarification of the diagnosis, while CT is valuable in
      the diagnosis of tumors of the axial skeleton as well as in systemic staging. A
      PET-CT can be performed to obtain an overview of further tumor sites. Open bone
      biopsy is the final diagnostic step and should be carried out at the institution
      where the definitive treatment will be performed. Complications such as fracture,
      neural lesions and spread of tumor cells are relatively rare if the biopsy is
      performed appropriately; however, patients should be instructed to strictly avoid
      weight-bearing on the affected extremity.

PMID- 21874364
TI  - Determinants of breast, cervical and colorectal cancer screening adherence in
      Mexican-American women.
AB  - Despite the effectiveness of cancer screening procedures, its utilization among
      Latinas remains low. Guided, in part, by the Behavioral Model for Vulnerable
      Populations, this study examined the associations between predisposing, enabling,
      and need factors with self-reported breast, cervical, and colorectal cancer
      screening adherence. Participants were 319 Mexican-American women, from a range
      of socioeconomic backgrounds, living near the United States-Mexico border. Women
      were adherent with breast cancer (BC) screening (>=42 years) if they had received
      at least one mammogram within the last 2 years, with cervical cancer (CC)
      screening (>=40 years) if they had received at least one Pap exam in the last 3
      years, and with colorectal cancer (CRC) screening (>=52 years) if they had
      undergone one or more of the following: Fecal Occult Blood Test within the last
      year, or sigmoidoscopy in the last 5 years, or colonoscopy within the last 10
      years. BC and CC screenings were higher in the current sample compared to
      national and state figures: 82% with mammography and 86% adherent with Pap exam
      screening. However, only 43% were adherent with CRC screening recommendations.
      Characteristics associated with mammography adherence included CC adherence and
      usual source of care. BC adherence was associated to CC adherence.
      Characteristics associated with CRC adherence included BC adherence, being
      premenopausal, and insurance coverage. A key correlate of cancer screening
      adherence was adherence to other preventive services. Results underscore the need
      for continued efforts to ensure that Latinas of all SES levels obtain regular and
      timely cancer screenings.

PMID- 21874365
TI  - Using survey results regarding hepatitis B knowledge, community awareness and
      testing behavior among Asians to improve the San Francisco Hep B Free campaign.
AB  - Asians are disproportionately affected by chronic hepatitis B (HBV) infection and
      its fatal consequences. The Hep B Free campaign was launched to eliminate HBV in
      San Francisco by increasing awareness, testing, vaccination and linkage to care.
      The campaign conducted 306 street intercept and telephone interviews of San
      Francisco Asians to assess current levels of HBV knowledge, testing behaviors and
      effectiveness of existing campaign media materials. One-third of respondents
      ranked HBV as a key health issue in the Asian community, second to diabetes.
      General HBV awareness is high (85%); however, a majority could not name an
      effective prevention method. Sixty percent reported having been tested for HBV;
      provider recommendation was the most often cited reason for testing. Respondents
      reported a high level of trust in their providers to correctly assess which
      health issues they may be at risk for developing and test accordingly, confirming
      that efforts to increase HBV testing among Asians must simultaneously mobilize
      the public to request testing and compel providers to test high-risk patients.
      Regarding community awareness, more than half reported hearing more about HBV
      recently; younger respondents were more likely to have encountered campaign
      materials and recall correct HBV facts. Assessment of specific campaign materials
      found that while upbeat images and taglines captured attention and destigmatized
      HBV, messages that emphasize the pervasiveness and deadly consequence of
      infection were more likely to drive respondents to seek education and testing.
      The campaign used survey results to focus efforts on more intensive provider
      outreach and to create messages for a new public outreach media campaign.

PMID- 21874366
TI  - A comparative study of gastric banding and sleeve gastrectomy in an obese
      diabetic rat model.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (SG) is now a typical restrictive
      bariatric procedure. The aim of this study was to evaluate the efficacy of SG in
      comparison with gastric banding (GB) in an obese diabetic rat model. METHODS:
      Forty-five male Zucker diabetic fatty rats were divided into three groups: sham
      operated (SO) control, GB, and SG. The rats were followed for 6 weeks after
      surgery, and their body weight change, cumulative food intake, metabolic
      parameters, plasma levels of ghrelin, glucagon-like peptide-1 and adiponectin,
      oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and gastric
      emptying rate were measured. RESULTS: The GB and SG groups showed significant
      decreases in weight, cumulative intake, and metabolic parameters and significant
      improvement of OGTT and ITT results compared with the SO group. There were no
      significant differences in weight and cumulative food intake between the groups.
      However, the SG group showed significantly higher gastric emptying rate and
      plasma level of adiponectin and lower plasma levels of free fatty acid, total
      cholesterol, and ghrelin compared with the GB group. Furthermore, the SG group
      showed improvement of OGTT and ITT results in comparison with the GB group.
      CONCLUSIONS: In obese diabetic rats, SG may improve glucose and lipid metabolism
      compared with GB, although there was no significant difference in the effect on
      body weight loss between the two procedures. The hormonal and digestive changes
      induced by SG may have relevance to the effects on metabolism.

PMID- 21874367
TI  - Letter to the editor: Long-term experience with duodenal switch in adolescents.

PMID- 21874368
TI  - The evaluation of the Croatian version of the Epworth sleepiness scale and STOP
      questionnaire as screening tools for obstructive sleep apnea syndrome.
AB  - PURPOSE: Growing awareness of obstructive sleep apnea syndrome (OSAS) has
      increased the need for concise and reliable screening tools. The Epworth
      sleepiness scale (ESS) has been validated in numerous languages and ethnic
      groups, since it was originally designed for the English-speaking population. The
      STOP questionnaire was developed as a novel OSAS screening tool in surgical
      patients, but has not been validated in the general population. The present study
      was undertaken to provide reliable and validated ESS in the Croatian language and
      to evaluate the ESS and STOP as screening instruments for OSAS. METHODS: The
      Croatian version of ESS and STOP questionnaire was administered to 217 patients
      referred to the Split Sleep Medicine Center and 208 healthy control subjects.
      Test-retest reliability was investigated in 20 healthy subjects. RESULTS: The ESS
      score was significantly higher for the patients referred to the Split Sleep
      Medicine Center compared to the control group (8.2 +/- 5.0 vs. 5.9 +/- 3.8, p <
      0.001). Cronbach's alpha coefficient for the ESS Croatian version was 0.84
      indicating an excellent internal consistency. Reproducibility revealed no
      significant difference in each item or in the total ESS scores. Receiver
      operating curve of the ESS for identification of cases with AHI >5/h was 0.64,
      and for the STOP questionnaire, it was 0.84. CONCLUSIONS: Both ESS and STOP
      questionnaires successfully distinguished healthy subjects from subjects with
      OSAS. The STOP questionnaire had better probability to correctly predict high
      risk patients for OSAS compared to ESS. We propose that the STOP questionnaire
      could be used as an easy-to-use and accurate screening tool in identification of
      patients with risk for OSAS in the general population, but it has not been tested
      in the Croatian population yet.

PMID- 21874369
TI  - Gastrointestinal endoscopy in patients with obstructive sleep apnea syndrome.

PMID- 21874370
TI  - Auto bi-level pressure relief-PAP is as effective as CPAP in OSA patients--a
      pilot study.
AB  - PURPOSE: Continuous positive airway pressure (CPAP) is the therapy of choice for
      the treatment of obstructive sleep apnea (OSA). Not all patients can use CPAP
      therapy with adequate compliance. There is a need to develop more comfortable
      modes. Auto bi-level Pressure Relief-Positive Airway Pressure (ABPR-PAP) can be
      an alternative. We conducted a prospective double-blind, randomised trial to
      evaluate the efficacy and compliance of ABPR-PAP compared with CPAP in OSA
      patients. METHODS: We included 35 CPAP naive patients (age 53.3 +/- 10.3 years,
      BMI 31.0 +/- 5.0 kg/m(2), ESS 10.0 +/- 4.2) diagnosed with moderate to severe OSA
      who underwent a successful CPAP titration. Patients were randomised into the CPAP
      or the ABPR-PAP treatment group. We used the same device (BIPAP(r) Auto, Philips
      Respironics) for CPAP or ABPR-PAP. Apnea-hypopnea index (AHI) was determined
      using polysomnography before (AHI 40.6 +/- 18.3 per hour) and after treatment.
      RESULTS: Eighteen patients received CPAP and the remaining 17 received APBR-PAP.
      Groups were similar in terms of demographics and OSA severity. There were no
      serious adverse events during the trial. CPAP was fixed by a sleep expert and
      ABPR-PAP varied (range 5-15 cmH(2)O). AHI decreased in the CPAP group to 6.4 +/-
      5.7 per hour and in the ABPR-PAP group to 4.8 +/- 3.6 per hour in the first night
      (N = 35). After 3 months, the AHI decreased in the CPAP group to 4.4 +/- 5.3 per
      hour and in the ABPR-PAP group to 2.6 +/- 3.8 per hour (N = 32). Differences
      between the groups were not statistically significant. There were no differences
      in compliance. CONCLUSIONS: ABPR-PAP is a promising new ventilation mode that
      enables effective treatment of OSA patients.

PMID- 21874371
TI  - A novel computer-assisted drill guide template for thoracic pedicle screw
      placement: a cadaveric study.
AB  - INTRODUCTION: The objective of this study was to develop a novel, patient
      specific, navigational template for thoracic pedicle screw placement. METHODS:
      Twenty thoracic cadaver specimens were randomly divided into two groups of 10:
      the navigational template group and the free-hand group. A volumetric CT scan was
      performed on each thoracic vertebra, and a three-dimensional reconstruction model
      was generated. A drill template was designed with a surface that was the inverse
      of the posterior vertebral surface. Each drill template and its corresponding
      vertebra were manufactured using a rapid prototyping technique and tested for
      violation. Two hundred and forty screws were implanted into the thoracic spines
      and the positions of the screws were evaluated. RESULTS: Two hundred and forty
      thoracic screws were inserted using either the navigational template method or
      the free-hand method. The accuracy rate and incidence of risk for setting
      thoracic pedicle screws differed statistically between the two methods (P <
      0.05): The navigational template method had a higher accuracy rate and a lower
      incidence of risk than the free-hand method. Moreover, the free-hand method had a
      significant learning curve, whereas a learning curve for the navigational
      template method was not obvious. CONCLUSION: We have developed a novel, patient
      specific, navigational template for thoracic pedicle screw placement with good
      applicability and high accuracy.

PMID- 21874373
TI  - The self-regulation of gambling.
AB  - Despite the prevalence of gambling world-wide, relatively few individuals become
      problem gamblers. Additionally many problem gamblers recover without professional
      assistance. The current study aim was to examine how individuals self-manage
      their gambling through (a) assessing frequency of use of a range of self
      regulation strategies (b) examining how these strategies cluster and (c)
      exploring relationships between strategies, gambling frequency, amount spent and
      problem gambling severity. A sample of 303 gamblers was recruited, over-sampling
      for problem gamblers as assessed by the Problem Gambling Severity Index (PGSI) of
      the Canadian Problem Gambling Index (mean age 26.4 years, SD = 10.1 years; 119
      males, 184 females; 238 social gamblers, 63 problem gamblers, 2 unclassified).
      They rated extent of usage of 27 gambling self-management techniques and
      completed the PGSI and other gambling measures. Factor analysis of items produced
      five factors, named Cognitive Approaches, Direct Action, Social Experience,
      Avoidance and Limit Setting. The relationships between these factors and key
      gambling variables were consistent with hypotheses that problem gamblers trying
      to reduce their gambling would be more likely to use the strategies than other
      gambler groups. The potential for developing the factors into a Gambling Self
      regulation Measure was explored.

PMID- 21874372
TI  - Alterations of blood brain barrier function in hyperammonemia: an overview.
AB  - Ammonia is a neurotoxin involved in the pathogenesis of neurological conditions
      associated with hyperammonemia, including hepatic encephalopathy, a condition
      associated with acute--(ALF) or chronic liver failure. This article reviews
      evidence that apart from directly affecting the metabolism and function of the
      central nervous system cells, ammonia influences the passage of different
      molecules across the blood brain barrier (BBB). A brief description is provided
      of the tight junctions, which couple adjacent cerebral capillary endothelial
      cells to each other to form the barrier. Ammonia modulates the transcellular
      passage of low-to medium-size molecules, by affecting their carriers located at
      the BBB. Ammonia induces interrelated aberrations of the transport of the large
      neutral amino acids and aromatic amino acids (AAA), whose influx is augmented by
      exchange with glutamine produced in the course of ammonia detoxification, and
      maybe also modulated by the extracellularly acting gamma-glutamyl moiety
      transferring enzyme, gamma-glutamyl-transpeptidase. Impaired AAA transport
      affects neurotransmission by altering intracerebral synthesis of catecholamines
      (serotonin and dopamine), and producing "false neurotransmitters" (octopamine and
      phenylethylamine). Ammonia also modulates BBB transport of the cationic amino
      acids: the nitric oxide precursor, arginine, and ornithine, which is an ammonia
      trap, and affects the transport of energy metabolites glucose and creatine.
      Moreover, ammonia acting either directly or in synergy with liver injury-derived
      inflammatory cytokines also evokes subtle increases of the transcellular passage
      of molecules of different size (BBB "leakage"), which appears to be responsible
      for the vasogenic component of cerebral edema associated with ALF.

PMID- 21874374
TI  - [Less blood culture samples: less infections?].
AB  - BACKGROUND: The data of the German hospital nosocomial infection surveillance
      system (KISS) were used to investigate the association between the frequency of
      blood cultures (BC) and central venous catheter associated bloodstream infection
      (CVC-BSI) rates in intensive care units (ICU). METHODS: A questionnaire on the
      frequency of BCs taken was sent to all ICUs participating in KISS and univariable
      and multivariable analyses were performed on the results. RESULTS: A total of 223
      ICUs provided data. The median number of BC pairs taken in 2006 was 60 with a
      huge variation from 3.2 to 680 per 1,000 patient days. The mean primary BSI rate
      was 0.90 per 1,000 patient days and 0.25 BSIs per 1,000 patient days were caused
      by coagulase negative Staphylococci (CNS). The mean CVC-BSI rate was 1.40 per
      1,000 CVC days. In the univariable analysis the blood culture frequency had a
      significant influence on the CVC-associated BSI rate, considering either all
      pathogens (p=0.001) or only the subgroup of CNS-related cases (p=0.019). There
      was also a significant influence of the BC frequency on the CVC-BSI rate
      considering all pathogens (p=0.004) as well as the subgroup of CNS (p=0.018).
      Therefore the BC frequency was a significant factor affecting the incidence of
      BSI and CVC-BSI. According to the multivariable analysis an increase of the BC
      frequency of 100 BCs per 1,000 patient days leads to a 1.27-fold higher incidence
      density of CVC-BSI with a 95% confidence interval (95% CI) of 1.01-1.26. A
      further significant risk factor for CVC-BSI was the length of stay in the ICU
      with an adjusted incidence rate ratio (IRR) of 1.25 (95% CI 1.15-1.35). To have
      the status of an interdisciplinary ICU was a significant protective factor (IRR
      0.64; 95% CI 0.45-0.92). CONCLUSIONS: If an external benchmarking of ICU CVC-BSI
      rates is intended an adjustment according to the BC frequency is necessary. The
      BC frequency itself should be established as a quality indicator in intensive
      care.

PMID- 21874375
TI  - Expression and significance of Six1 and Ezrin in cervical cancer tissue.
AB  - This study aimed to investigate the expression of Six1 gene and its downstream
      target gene Ezrin in cervical cancer, and to correlate their expression to the
      clinical pathology of cervical cancer. RT-PCR and Western blot were used to
      detect the expression of Six1 and Ezrin in cervical cancer tissue, cervical
      intraepithelial neoplasia tissue, and normal cervical tissue. The correlation of
      Six1 and Ezrin expression with the occurrence, development, and clinical
      pathology of cervical cancer was then analyzed. The expression of Six1 and Ezrin
      mRNA and protein in cervical cancer and cervical intraepithelial neoplasia was
      significantly higher than in normal cervical tissue (p < 0.05). Their expression
      was also significantly higher in the cancerous tissues of patients with advanced
      cervical cancer than in those of patients with early-stage cervical cancer (p <
      0.05). Moreover, they were expressed at significantly higher levels in lymph node
      metastasis-positive patients than in lymph node metastasis-negative patients (p <
      0.05). Finally, we observed that lesser differentiated tumors had elevated
      expression of Six1 and Ezrin mRNA and protein (p < 0.05). However, the mRNA and
      protein expression of Six1 and Ezrin were independent of patient age and tumor
      size (p > 0.05). Further investigation is warranted to describe the relation of
      whether Six1 and Ezrin protein contributes to the mechanism of occurrence,
      development, differentiation, and invasiveness of the tumor. These markers could
      be used as indicators of prognosis in early-stage cervical cancer as Six1 and
      Ezrin had a synergistic effect on the incidence of cervical cancer.

PMID- 21874376
TI  - Budget impact analysis in economic evaluation: a proposal for a clearer
      definition.

PMID- 21874380
TI  - Lipid resuscitation reverses multidrug-induced cardiogenic shock.

PMID- 21874378
TI  - MicroRNAs and their diverse functions in plants.
AB  - microRNAs (miRNAs) are an extensive class of newly identified small RNAs, which
      regulate gene expression at the post-transcriptional level by mRNA cleavage or
      translation inhibition. Currently, there are 3,070 miRNAs deposited in the public
      available miRNA database; these miRNAs were obtained from 43 plant species using
      both computational (comparative genomics) and experimental (direct cloning and
      deep sequencing) approaches. Like other signaling molecules, plant miRNAs can
      also be moved from one tissue to another through the vascular system. These
      mobile miRNAs may play an important role in plant nutrient homeostasis and
      response to environmental biotic and abiotic stresses. In addition, miRNAs also
      control a wide range of biological and metabolic processes, including
      developmental timing, tissue-specific development, and stem cell maintenance and
      differentiation. Currently, a majority of plant miRNA-related researches are
      purely descriptive, and provide no further detailed mechanistic insight into
      miRNA-mediated gene regulation and other functions. To better understand the
      function and regulatory mechanisms of plant miRNAs, more strategies need to be
      employed to investigate the functions of miRNAs and their associated signaling
      pathways and gene networks. Elucidating the evolutionary mechanism of miRNAs is
      also important. It is possible to develop a novel miRNA-based biotechnology for
      improving plant yield, quality and tolerance to environmental biotic and abiotic
      stresses besides focusing on basic genetic studies.

PMID- 21874377
TI  - Transduction of human recombinant proteins into mitochondria as a protein
      therapeutic approach for mitochondrial disorders.
AB  - Protein therapy is considered an alternative approach to gene therapy for
      treatment of genetic-metabolic disorders. Human protein therapeutics (PTs),
      developed via recombinant DNA technology and used for the treatment of these
      illnesses, act upon membrane-bound receptors to achieve their pharmacological
      response. On the contrary, proteins that normally act inside the cells cannot be
      developed as PTs in the conventional way, since they are not able to "cross" the
      plasma membrane. Furthermore, in mitochondrial disorders, attributed either to
      depleted or malfunctioned mitochondrial proteins, PTs should also have to reach
      the subcellular mitochondria to exert their therapeutic potential. Nowadays,
      there is no effective therapy for mitochondrial disorders. The development of
      PTs, however, via the Protein Transduction Domain (PTD) technology offered new
      opportunities for the deliberate delivery of human recombinant proteins inside
      eukaryotic subcellular organelles. To this end, mitochondrial disorders could be
      clinically encountered with the delivery of human mitochondrial proteins
      (engineered via recombinant DNA and PTD technologies) at specific
      intramitochondrial sites to exert their function. Overall, PTD-mediated Protein
      Replacement Therapy emerges as a suitable model system for the therapeutic
      approach for mitochondrial disorders.

PMID- 21874382
TI  - Individual filamentous phage imaged by electron holography.
AB  - An in-line electron hologram of an individual f1.K phage was recorded with a
      purpose-built low energy electron point source (LEEPS) microscope. Cryo
      microscopic methods were employed to prepare the specimen so that a single phage
      could be presented to the coherent low energy electrons: An aqueous phage
      suspension was applied to a thin carbon membrane with micro-machined slits. The
      membrane was rapidly cooled to freeze the remaining water as an amorphous ice
      sheet, which was then sublimated at low temperatures and pressures to leave
      individual free-standing phages suspended across slits. An image of a phage
      particle, depicted as the amplitude of the object wave, was reconstructed
      numerically from a digitized record of the hologram, obtained using 88 eV
      coherent electrons. The reconstructed image shows a single phage suspended across
      a slit in a supporting carbon membrane, magnified by a factor of 100,000. The
      width and shape in the reconstructed image compared well with a TEM image of the
      same filament. It is thus possible to record and reconstruct electron holograms
      of an individual phage. The challenge now is to improve the resolution of
      reconstructed images obtained by this method and to extend these structural
      studies to other biological molecules.

PMID- 21874381
TI  - Biophysical studies of an NAD(P)(+)-dependent aldehyde dehydrogenase from
      Bacillus licheniformis.
AB  - Aldehyde dehydrogenase (ALDH) catalyzes the conversion of aldehydes to the
      corresponding acids by means of an NAD(P)(+)-dependent virtually irreversible
      reaction. In this investigation, the biophysical properties of a recombinant
      Bacillus licheniformis ALDH (BlALDH) were characterized in detail by analytical
      ultracentrifuge (AUC) and various spectroscopic techniques. The oligomeric state
      of BlALDH in solution was determined to be tetrameric by AUC. Far-UV circular
      dichroism analysis revealed that the secondary structures of BlALDH were not
      altered in the presence of acetone and ethanol, whereas SDS had a detrimental
      effect on the folding of the enzyme. Thermal unfolding of this enzyme was found
      to be highly irreversible. The native enzyme started to unfold beyond ~0.2 M
      guanidine hydrochloride (GdnHCl) and reached an unfolded intermediate,
      [GdnHCl](05, N-U), at 0.93 M. BlALDH was active at concentrations of urea below 2
      M, but it experienced an irreversible unfolding under 8 M denaturant. Taken
      together, this study provides a foundation for the future structural
      investigation of BlALDH, a typical member of ALDH superfamily enzymes.

PMID- 21874383
TI  - Adult medulloblastoma: multiagent chemotherapy with cisplatinum and etoposide: a
      single institutional experience.
AB  - In 1991, a prospective phase II trial was initiated to evaluate the efficacy of
      treatment for adults with medulloblastoma (MB). After surgery, patients were
      staged with a neuroradiologic examination of the brain and neuroaxis and by
      cerebrospinal fluid cytology. All patients received three cycles of upfront
      cisplatinum (cisplatinum) and etoposide (VP16) chemotherapy followed by cranio
      spinal radiation therapy. The current article reports on the long-term results
      from that trial. After a median follow-up of 14.9 years, among a total of 28
      adults with MB, the overall progression-free survival and overall survival (OS)
      rates at 5 years were 57.6 and 80%, respectively. The median OS for the whole
      group of patients was 11.3 years. The observed toxicity was mainly hematological,
      with leukopenia and thrombocytopenia (16% of grades 3 and 4). In summary, in our
      small series of patients, the role of combination administration of CDDP + VP16
      started before the initiation of radiotherapy in reducing recurrences,
      particularly distant recurrences, remains unclear. To know whether adding
      chemotherapy to craniospinal radiation in adult therapy increases relapse-free
      and overall survival, we must await the results of a larger randomized controlled
      clinical trial.

PMID- 21874384
TI  - Germinoma occurring 2 years after total resection of an intracranial epidermoid
      cyst in the pineal region.

PMID- 21874385
TI  - Difficulty assisting with health care tasks among caregivers of multimorbid older
      adults.
AB  - BACKGROUND: Family caregivers provide assistance with health care tasks for many
      older adults with chronic illnesses. The difficulty they experience in providing
      this assistance, and related implications for their well-being, have not been
      well described. OBJECTIVE: The objectives of this study are: (1) to describe
      caregiver's health care task difficulty (HCTD), (2) determine the characteristics
      associated with HCTD, and (3) explore the association between HCTD and caregiver
      well-being. DESIGN: This is a cross-sectional study. PARTICIPANTS: Baseline
      sample of caregivers to older (aged 65+ years) multimorbid adults enrolled in an
      ongoing cluster-randomized controlled trial (N = 308). MAIN MEASURES: The HCTD
      scale (0-16) is comprised of questions measuring self-reported difficulty in
      assisting older adults with eight health care tasks, including taking medication,
      visiting health care providers, and managing medical bills. Caregivers were
      categorized using this scale into no, low, medium, and high HCTD groups. We used
      ordinal logistic regression and multivariate linear regression analyses to
      examine the relationships between HCTD, caregiver self-efficacy, caregiver strain
      (Caregiver Strain Index), and depression (Center for Epidemiological Studies
      Depression Scale), controlling for patient and caregiver socio-demographic and
      health factors. KEY RESULTS: Caregiver age and number of health care tasks
      performed were positively associated with increased HCTD. The quality of the
      caregiver's relationship with the patient, and self-efficacy were inversely
      associated with increased HCTD. A one-point increase in self-efficacy was
      associated with a significant lower odds of reporting high HCTD (OR, 0.64; 95%
      CI, 0.54, 0.77).Adjusted linear regression models indicated that high HCTD was
      independently associated with significantly greater caregiver strain (B, 2.7; 95%
      CI, 1.12, 4.29) and depression (B, 3.01; 95% CI, 1.06, 4.96). CONCLUSIONS: This
      study demonstrates that greater HCTD is associated with increased strain and
      depression among caregivers of multimorbid older adults. That caregiver self
      efficacy was strongly associated with HCTD suggests health-system-based
      educational and empowering interventions might improve caregiver well-being.

PMID- 21874386
TI  - Hypomethylation of functional retrotransposon-derived genes in the human
      placenta.
AB  - DNA hypomethylation is assumed to be a feature of the mammalian placenta;
      however, its role in regulating placental gene expression is not well defined. In
      this study, MeDIP and Sequenom MassARRAY were used to identify hypomethylated
      gene promoters in the human placenta. Among the genes identified, the
      hypomethylation of an alternative promoter for KCNH5 was found to be restricted
      to the placenta and chorion. Complete methylation of this promoter correlates
      with a silenced KCNH5 transcript in embryonic tissues, including the amnion.
      Unusually, this hypomethylated promoter and the alternative first exon are
      derived from a SINE (AluY) retrotransposon. Examination of additional
      retrotransposon-derived gene promoters in the placenta confirmed that
      retrotransposon hypomethylation permits the placenta-specific expression of these
      genes. Furthermore, the lineage-specific methylation displayed by KCNH5, INSL4,
      and ERVWE1 revealed that dichotomous methylation establishes differential
      retrotransposon silencing between the extra-embryonic and embryonic lineages. The
      hypomethylation of the retrotransposons that regulate these genes, each of which
      arose during recent primate evolution, is consistent with these genes having
      functional roles that are unique to the invasive haemochorial placentas of humans
      and recent primates.

PMID- 21874387
TI  - The (un)managed self: paradoxical forms of agency in self-management of bipolar
      disorder.
AB  - Self-management of mental illness is a therapeutic paradigm that draws on a
      distinctly biomedical conceptualization of the isolability of personhood from
      pathology. This discourse posits a stable and rational patient/consumer who can
      observe, anticipate, and preside over his disease through a set of learned
      practices. But in the case of bipolar disorder, where the rationality of the
      patient is called into question, the managing self is elusive, and the disease
      that is managed coincides with the self. While humanist critiques of the
      biomedical model as applied to mental illness have argued that its logic
      fatalistically denies patients intentionality and effectiveness (Luhrmann, Of Two
      Minds: The Growing Disorder in American Psychiatry, 2000), biomedical proponents
      claim that psychiatry's way of envisioning the body as under the control of the
      intentional mind actually returns agency to the patient/consumer. Rose (The
      Psychiatric Gaze, 1999) remarks that biomedical models have the potential to
      "[open] that which was considered natural to a form of choice" (p. 37), and that
      techniques of medical self-control help constitute the free embodied liberal
      subject who is obliged to calculate and choose. Through an examination of
      clinical literature as well as the practices and narratives of members of a
      bipolar support group, this paper explores ethnographically the possibilities for
      subjectivity and agency that are conditioned or foreclosed by the self-management
      paradigm, which seems to simultaneously confer and deny rational selfhood to
      bipolar patients. To express their expertise as rational self-managers,
      patients/consumers must, paradoxically, articulate constant suspicion toward
      their present thoughts and emotions, and distrust of an imagined future self. I
      argue that through their self-management practices, bipolar support group members
      model provisional and distributed forms of agency based on an elusive,
      discontinuous, and only partially knowable or controllable self-revealing,
      perhaps, the limits of the contemporary reification and medicalization of both
      selfhood and disease.

PMID- 21874389
TI  - Posterior cruciate ligament and posterolateral corner deficiency results in a
      reverse pivot shift.
AB  - BACKGROUND: As measured via static stability tests, the PCL is the dominant
      restraint to posterior tibial translation while the posterolateral corner is the
      dominant restraint to external tibial rotation. However, these uniplanar static
      tests may not predict multiplanar instability. The reverse pivot shift is a
      dynamic examination maneuver that may identify complex knee instability.
      QUESTIONS/PURPOSES: In this cadaver study, we asked whether (1) isolated
      sectioning or (2) combined sectioning of the PCL and posterolateral corner
      increased the magnitude of the reverse pivot shift and (3) the magnitude of the
      reverse pivot shift correlated with static external rotation or posterior drawer
      testing. METHODS: In Group I, we sectioned the PCL followed by structures of the
      posterolateral corner. In Group II, we sectioned the posterolateral corner
      structures before sectioning the PCL. We performed posterior drawer, external
      rotation tests, and mechanized reverse pivot shift for each specimen under each
      condition and measured translations via navigation. RESULTS: Isolated sectioning
      of the PCL or posterolateral corner had no effect on the reverse pivot shift.
      Conversely, combined sectioning of the PCL and posterolateral corner structures
      increased the magnitude of the reverse pivot shift. The magnitude of the reverse
      pivot shift correlated with the posterior drawer and external rotation tests.
      CONCLUSIONS: Combined sectioning of the PCL and posterolateral corner was
      required to cause an increase in the magnitude of the mechanized reverse pivot
      shift. The reverse pivot shift correlated with both static measures of stability.
      CLINICAL RELEVANCE: Combined injury to the PCL and posterolateral corner should
      be considered in the presence of a positive reverse pivot shift.

PMID- 21874388
TI  - A multimode optical imaging system for preclinical applications in vivo:
      technology development, multiscale imaging, and chemotherapy assessment.
AB  - PURPOSE: Several established optical imaging approaches have been applied,
      usually in isolation, to preclinical studies; however, truly useful in vivo
      imaging may require a simultaneous combination of imaging modalities to examine
      dynamic characteristics of cells and tissues. We developed a new multimode
      optical imaging system designed to be application-versatile, yielding high
      sensitivity, and specificity molecular imaging. PROCEDURES: We integrated several
      optical imaging technologies, including fluorescence intensity, spectral,
      lifetime, intravital confocal, two-photon excitation, and bioluminescence, into a
      single system that enables functional multiscale imaging in animal models.
      RESULTS: The approach offers a comprehensive imaging platform for kinetic,
      quantitative, and environmental analysis of highly relevant information, with
      micro-to-macroscopic resolution. Applied to small animals in vivo, this provides
      superior monitoring of processes of interest, represented here by chemo
      /nanoconstruct therapy assessment. CONCLUSIONS: This new system is versatile and
      can be optimized for various applications, of which cancer detection and targeted
      treatment are emphasized here.

PMID- 21874390
TI  - Can computer assistance improve the clinical and functional scores in total knee
      arthroplasty?
AB  - BACKGROUND: Surgical navigation in TKA facilitates better alignment; however, it
      is unclear whether improved alignment alters clinical evolution and midterm and
      long-term complication rates. QUESTIONS/PURPOSES: We determined the alignment
      differences between patients with standard, manual, jig-based TKAs and patients
      with navigation-based TKAs, and whether any differences would modify function,
      implant survival, and/or complications. PATIENTS AND MATERIALS: We
      retrospectively reviewed 97 patients (100 TKAs) undergoing TKAs for minimal
      preoperative deformities. Fifty TKAs were performed with an image-free surgical
      navigation system and the other 50 with a standard technique. We compared femoral
      angle (FA), tibial angle (TA), and femorotibial angle (FTA) and determined
      whether any differences altered clinical or functional scores, as measured by the
      Knee Society Score (KSS), or complications. Seventy-three patients (75 TKAs) had
      a minimum followup of 8 years (mean, 8.3 years; range, 8-9.1 years). RESULTS: All
      patients included in the surgical navigation group had a FTA between 177 degrees 
      and 182o. We found no differences in the KSS or implant survival between the two
      groups and no differences in complication rates, although more complications
      occurred in the standard technique group (seven compared with two in the surgical
      navigation group). CONCLUSIONS: In the midterm, we found no difference in
      functional and clinical scores or implant survival between TKAs performed with
      and without the assistance of a navigation system. LEVEL OF EVIDENCE: Level II,
      therapeutic study. See the Guidelines online for a complete description of levels
      of evidence.

PMID- 21874391
TI  - Patient-related risk factors for postoperative mortality and periprosthetic joint
      infection in medicare patients undergoing TKA.
AB  - BACKGROUND: The impact of specific baseline comorbid conditions on the relative
      risk of postoperative mortality and periprosthetic joint infection (PJI) in
      elderly patients undergoing TKA has not been well defined. QUESTIONS/PURPOSES: We
      calculated the relative risk of postoperative mortality and PJI associated with
      29 comorbid conditions in Medicare patients undergoing TKA. PATIENTS AND METHODS:
      The Medicare 5% sample was used to calculate the relative risk of 90-day
      postoperative mortality and PJI as a function of 29 preexisting comorbid
      conditions in 83,011 patients who underwent primary TKA between 1998 and 2007.
      RESULTS: The independent risk factors for 90-day postoperative mortality (in
      decreasing order of significance) were congestive heart failure, metastatic
      cancer, renal disease, peripheral vascular disease, cerebrovascular disease,
      lymphoma, cardiac arrhythmia, dementia, pulmonary circulation disorders, and
      chronic liver disease. The independent risk factors for PJI (in decreasing order
      of significance) were congestive heart failure, chronic pulmonary disease,
      preoperative anemia, diabetes, depression, renal disease, pulmonary circulation
      disorders, obesity, rheumatologic disease, psychoses, metastatic tumor,
      peripheral vascular disease, and valvular disease. CONCLUSIONS: We believe this
      information important when counseling elderly patients regarding the risks of
      mortality and PJI after TKA and risk-adjusting publicly reported TKA patient
      outcomes.

PMID- 21874392
TI  - Addressing trauma in mental health and substance use treatment.
AB  - Individuals with histories of violence, abuse, and neglect from childhood onward
      make up the majority of clients served by public mental health and substance
      abuse service systems. The greater the trauma, the greater the risk for
      alcoholism and alcohol abuse, depression, illicit drug use, suicide attempts, and
      other negative outcomes. Clearly, we cannot begin to address the totality of an
      individual's healthcare, or focus on promoting health and preventing disease,
      unless we address trauma. Trauma-informed care is now the expectation, not the
      exception, in behavioral health treatment systems.

PMID- 21874394
TI  - Challenges to expanding the clinical application of musculoskeletal
      ultrasonography (MSUS) among rheumatologists: from a second survey in Japan.
AB  - Our previous survey in 2008 revealed that only 22% of Japanese rheumatologists
      used musculoskeletal ultrasonography (MSUS) for patient management, because of
      insufficient educational opportunities. To clarify the current state of MSUS
      usage and to identify further challenges, we conducted a second survey between
      October 2010 through January 2011 by sending questionnaires to 200 randomly
      selected Japanese rheumatologists, consisting of 100 participants in a meeting in
      2009 on imaging in rheumatic diseases and 100 board-certified rheumatologists.
      Among the respondents, a majority (85 and 67%, respectively) used magnetic
      resonance imaging (MRI). MSUS users had increased from 32 to 60% of meeting
      participants and from 11 to 27% of other rheumatologists. The majority of MSUS
      users had begun using MSUS within the previous 3 years. Whereas most respondents
      in the previous survey had been self-taught, in the current survey many had
      attended training courses or had received informal training from skilled users.
      Despite an increase in skills and equipment ownership, obstacles to implementing
      MSUS remained, most prominently a lack of time. In conclusion, training courses
      and informal training have contributed to the popularization of MSUS in Japan. To
      further increase MSUS usage, additional training opportunities and education
      about the advantages of MSUS will be needed.

PMID- 21874393
TI  - Novel method of measuring patellar height ratio using a distal femoral reference
      point.
AB  - PURPOSE: Patellar height is an important factor in patellar tracking and alters
      the force of the patellofemoral joint reaction. Several methods for measuring
      patellar height ratio have been described, with no single method recognised as a
      gold standard. This study developed a new measurement method using a distal
      femoral reference, where the normal values of measurement are unaffected by
      varying angles of knee flexion. METHODS: Eighty-five volunteers had radiographs
      taken of their knees at 0 degrees , 15 degrees , 30 degrees , 45 degrees  and 60
      degrees  of flexion in a supine position. Patellar height was assessed by five
      different measurement methods: Insall-Salvati (IS), modified Insall-Salvati
      (MIS), Caton-Deschamps (CD), Blackburne-Peel (BP) and our new method. Three
      independent examiners sequentially conducted all measurements under identical
      conditions. RESULTS: The normal value obtained with the method reported here was
      1 +/- 0.1 standard deviation (SD) (IS 1.1 +/- 0.2, MIS 1.8 +/- 0.25, CD 1.08 +/-
      0.2, BP 0.9 +/- 0.2). IS and the new method tended to have better reliability in
      the face of varying knee-flexion angles than did CD, BP or MIS. All methods had
      good to excellent levels of interobserver variation (IS 0.969, new method 0.811,
      MIS 0.768, CD 0.735, BP 0.708). CONCLUSION: The new patellar height ratio
      measurement method proved to be accurate and reproducible for evaluating a normal
      population. This method offered the benefit of using the distal femur as a
      reference landmark, and, thus, the resulting measurements were not altered by
      varying degrees of knee flexion.

PMID- 21874395
TI  - Perceived control mediates the prospective impact of relationship quality in the
      year after colorectal cancer diagnosis.
AB  - BACKGROUND: Negative cancer-related intrusive thoughts reduce the benefit of
      relationship quality on the psychological adjustment of cancer patients. Little
      is known about the role of perceived control over cancer-related problems in the
      association between relationship quality and adjustment. PURPOSE: This study
      examined whether perceived personal control (i.e., on one's own) and collective
      control (i.e., collaboration with family/friends) mediate the associations
      between relationship quality and psychological outcomes. METHODS: Chinese
      colorectal cancer patients (n = 234) were assessed at diagnosis (T1) and at 3-
      (T2) and 12-month (T3) follow-ups. RESULTS: T2 collective control mediated the
      association between T1 family relationship quality and T3 satisfaction with life.
      The negative association between T1 family relationship quality and T3 depression
      was independent of T2 personal/collective control. CONCLUSIONS: Collective
      control mediates the relationship between family relationship quality and
      satisfaction with life, suggesting the need for interventions to enhance
      relationship quality and perceived control among newly diagnosed cancer patients.

PMID- 21874396
TI  - Brief report: The assessment of anxiety in high-functioning adolescents with
      autism spectrum disorder.
AB  - Anxiety may exacerbate interpersonal difficulties and contribute to secondary
      behavioral problems in adolescents with High-Functioning Autism Spectrum Disorder
      (HFASD). This study was conducted to assess the psychometric properties and
      construct validity of measures of anxiety with a sample (n = 30) of adolescents
      with HFASD and comorbid anxiety disorders. Results indicate that the measures
      (CASI-Anxiety Scale; Sukhodolsky et al. 2008; MASC; March 1998) possess
      acceptable internal consistency, and there is evidence of discriminant validity.
      Most of the adolescents, however, under-reported problems with anxiety, compared
      to parent-reported and clinician-derived reports and given they were seeking
      treatment for anxiety problems. Findings highlight the importance of using
      multiple raters in clinical practice and consideration of rater discrepancies in
      clinical research.

PMID- 21874397
TI  - Effect of water stress and fungal inoculation on monoterpene emission from an
      historical and a new pine host of the mountain pine beetle.
AB  - The mountain pine beetle (Dendroctonus ponderosae, MPB) has killed millions of
      lodgepole pine (Pinus contorta) trees in Western Canada, and recent range
      expansion has resulted in attack of jack pine (Pinus banksiana) in Alberta.
      Establishment of MPB in the Boreal forest will require use of jack pine under a
      suite of environmental conditions different from those it typically encounters in
      its native range. Lodgepole and jack pine seedlings were grown under controlled
      environment conditions and subjected to either water deficit or well watered
      conditions and inoculated with Grosmannia clavigera, a MPB fungal associate. Soil
      water content, photosynthesis, stomatal conductance, and emission of volatile
      organic compounds (VOCs) were monitored over the duration of the six-week study.
      Monoterpene content of bark and needle tissue was measured at the end of the
      experiment. beta-Phellandrene, the major monoterpene in lodgepole pine, was
      almost completely lacking in the volatile emission profile of jack pine. The
      major compound in jack pine was alpha-pinene. The emission of both compounds was
      positively correlated with stomatal conductance. 3-Carene was emitted at a high
      concentration from jack pine seedlings, which is in contrast to monoterpene
      profiles of jack pine from more southern and eastern parts of its range. Fungal
      inoculation caused a significant increase in total monoterpene emission in water
      deficit lodgepole pine seedlings right after its application. By 4 weeks into the
      experiment, water deficit seedlings of both species released significantly lower
      levels of total monoterpenes than well watered seedlings. Needle tissue contained
      lower total monoterpene content than bark. Generally, monoterpene tissue content
      increased over time independent from any treatment. The results suggest that
      monoterpenes that play a role in pine-MPB interactions differ between lodgepole
      and jack pine, and also that they are affected by water availability.

PMID- 21874398
TI  - Positive predictive value of the Xpert MRSA assay diagnostic for universal
      patient screening at hospital admission: influence of the local ecology.
AB  - The purpose of this study was to assess the accuracy of the Xpert MRSA assay (XP)
      for the detection of methicillin-resistant Staphylococcus aureus (MRSA) carriage
      upon hospital admission. Nasal swabs were prospectively collected for MRSA
      screening from 1,891 patients admitted to a teaching hospital. XP results were
      compared to chromogenic agar culture results. MRSA was cultured in 61 specimens
      (3%). Compared with culture, XP had a sensitivity, specificity, positive, and
      negative predictive value of 60.7, 97.3, 37.8, and 98.9%, respectively. The
      median turnaround time (TAT) for the results was 3 h. Of 24 MRSA isolated from XP
      negative samples, three harbored composite SCCmec. Among 61 samples with culture
      negative but XP-positive results, 15 methicillin-susceptible S. aureus (MSSA)
      isolates tested positive by XP on pure colony lysates. These MSSA included: (i)
      strains with SCCmec deletion encompassing mecA and (ii) multilocus sequence
      typing (MLST) clonal complex (CC) 1 strains harboring a chromosomal sequence
      homologous to one of the orfX-SCCmec junction sequences targeted by XP. On
      account of the low sensitivity and positive predictive value in a hospital
      patient population with moderate prevalence of MRSA, culture still appears to be
      necessary in order to confirm polymerase chain reaction (PCR) results. The
      emergence of new SCCmec variants and the presence of MSSA harboring cross
      reactive SCCmec-like elements may challenge the successful implementation of such
      detection systems.

PMID- 21874399
TI  - Antibody response to Haemophilus influenzae type-b conjugate vaccine in children
      and young adults with congenital asplenia or after undergoing splenectomy.
AB  - Absence of the spleen constitutes a risk of infection caused by encapsulated
      bacteria. The aim of our study was to determine the immune response to
      Haemophilus influenzae type-b (Hib) conjugate vaccine (HibCV) in asplenic
      individuals, considering the cause of asplenia, the age when splenectomy was
      carried out, and previous Hib vaccinations. Twenty asplenic patients, aged five
      to 25 years, were immunized with a single dose of HibCV. The specific antibody
      concentrations against HibCV were measured by enzyme-linked immunosorbent assay.
      Before vaccinations, the geometric mean antibody concentration (GMC) had an
      average value of 3.21 MUg/ml and was comparable for all of the patients,
      regardless of the causes of asplenia. After vaccinations, the GMC was
      significantly higher, with an average of 6.78 MUg/ml. Further, 4.5 years after
      vaccinations, the GMC was comparable to that of previously unvaccinated children.
      Moreover, 17/20 patients had GMC >= 1.0 MUg/ml, which included all of the
      children with congenital asplenia, children splenectomized before the age of six
      years, and only 57% of children splenectomized after that age. HibCV gives
      asplenic patients long-term protection. Hence, HibCV should be administered
      regardless of previous vaccinations and time from splenectomy, even if antibody
      evaluation is not available.

PMID- 21874400
TI  - Specificity of learning through memory retrieval practice: the case of addition
      and subtraction.
AB  - The identical elements (IE) model (Rickard, Healy, & Bourne, Learning, Memory,
      and Cognition 32:734-748, 1994) of fact representation predicts that, in both
      verbal and numerical domains, performance gains with retrieval practice on
      multielement items will be specific to the practiced stimulus-response
      combinations, failing to transfer even to altered stimulus-response mappings of
      practiced items. In the case of arithmetic, the model predicts no transfer across
      either complementary operations (e.g., 4 * 7 to 28 / 4) or complementary division
      or subtraction problems (e.g., 28 / 4 to 28 / 7). Although that model has
      successfully described transfer effects in the domains of multiplication-division
      and episodic cued recall, it is challenged by a recent demonstration of positive
      cross-operation transfer for addition and subtraction (Campbell & Agnew,
      Psychonomic Bulletin & Review 16:938-944, 2009). We report results of a new
      addition-subtraction transfer experiment, the design of which closely matched
      that of a prior multiplication-division experiment that supported the model. The
      transfer results were consistent with the IE model. A two-component model of
      memory retrieval practice effects is proposed to account for the discrepant
      experimental results for addition and subtraction and to guide future work.

PMID- 21874401
TI  - IJBM - interdisciplinary, international, and outstanding research on factors
      relevant to health and illness.

PMID- 21874402
TI  - C-reactive protein is associated with the progression of acute embolic stroke in
      rabbit model.
AB  - Several lines of evidence have shown that plasma C-reactive protein (CRP) is
      associated with increased risk of stroke; however, previous studies were not
      adequately powered to assess whether plasma CRP levels are associated with stroke
      progression. In the current study, we designed a rabbit stroke model and
      investigated the relationship between plasma CRP and infarcted brain tissue. To
      produce a rabbit stroke model, we injected autologous thrombi into the left
      internal carotid artery. The plasma CRP levels were measured by ELISA at 0.5, 3,
      6, 9, and 12 h poststroke. At 12 h, the rabbits were sacrificed, and the whole
      brains were examined by H & E and immunohistochemical staining with a monoclonal
      antibody against rabbit CRP. CRP mRNA expression in the infarcted tissue was
      evaluated by RT-PCR. Plasma CRP was markedly increased after embolic stroke.
      Plasma CRP positively correlated with the cerebral infarct area (r = 0.98, P <
      0.01). Immunohistochemical staining revealed that CRP was frequently present in
      the infarcted area but not in normal cerebral tissue. RT-PCR showed that CRP was
      expressed in infarcted brain tissue. The plasma CRP level was significantly
      elevated after stroke and was closely correlated with the size of infarction,
      suggesting that CRP is an ideal marker to assess the acute embolic stroke.

PMID- 21874403
TI  - Antioxidant responses and bioaccumulation in green-lipped mussels (Perna viridis)
      under acute tributyltin chloride exposure.
AB  - Green-lipped mussels (Perna viridis) were exposed to waterborne tributyltin
      chloride (TBTCl) at different concentrations (0.2, 0.4 and 0.8 MUg L(-1)) for up
      to 72 h. Accumulated TBTCl in Perna viridis correlated linearly with the exposure
      concentrations of 0.2 MUg L(-1)(R(2) = 0.772), 0.4 MUg L(-1)(R(2) = 0.952), and
      0.8 MUg L(-1)(R(2) = 0.909). The results of superoxide dismutase (SOD),
      glutathione peroxidase (GPx) and malondialdehyde (MDA) all decreased in gill
      tissues after 24 h of exposure, but the hepatic SOD and the hepatic GPx showed
      either little or no effect on exposure of TBTCl solutions. Analysis using the
      Spearman rank correlation coefficient showed the hepatic GPx activity appeared to
      have a significant negative correlativity (R(s) = -0.42) with the exposed TBTCl
      concentrations, and the hepatic MDA was significantly negatively correlated (R(s)
      = -0.33) with the tissue TBTCl concentrations. Conversely, a significant positive
      correlation (R(s) = 0.60) was shown between the gill MDA contents and exposure
      time. This study illustrates oxyradical scavenger GPx best correlated with stress
      level of pollutants among the various antioxidant parameters.

PMID- 21874404
TI  - Mercury distribution in organs of two species of fish from Amazon region.
AB  - Total mercury concentrations were determined in muscle, liver and kidney of
      Cichlia ocellaris and Colossoma macropomum sampled at Tapajos and Carnapijo
      Rivers in Amazon ecosystem during the flood period of 2009. In background area
      the highest levels of mercury were observed in liver of piscivorous (0.3 +/- 0.03
      ug/g dry wt) and non piscivorous fish (0.20 +/- 0.1 ug/g dry wt), but in
      contaminated area the highest level of mercury in piscivorous fish was detected
      in liver (0.45 +/- 0.27 ug/g dry wt) and in muscle (0.26 +/- 0.05 ug/g dry wt) of
      non piscivorous fish. These results suggested that the presence of anthropogenic
      source plays a key role in the pattern of mercury distribution in fish tissues.

PMID- 21874405
TI  - Serum and synovial fluid levels of interleukin-17 in correlation with disease
      activity in patients with RA.
AB  - The aim of this study was to evaluate serum and synovial levels of IL-17A by
      ELISA in rheumatoid arthritis (RA) and find out the correlations between IL-17A
      levels and various clinical, laboratory parameters and RA disease activity and
      severity indices. Group I consists of 30 adult active RA patients fulfilling the
      ARA 1987 revised criteria, with knee effusion and receiving basic therapy, and
      with a mean age of 41.47+/-11.49 years and mean disease duration of 9.5+/-4.16
      years. Group II consisted of 13 healthy volunteers, age- and sex-matched, with a
      mean age of 39.08+/-14.19 years. RA patients showed significantly higher mean
      serum IL-17A levels than controls (11.25+/-9.67 vs. 0.6+/-1.4 pg/mL,
      respectively, p=0.0002). Synovial IL-17A levels showed a significant positive
      correlation with serum IL-17A levels (r=0.5 and p=0.005). RA patients with
      negative rheumatoid factor (RF) had non-significantly higher mean serum IL-17A
      levels (12+/-9.86 pg/mL) compared to those with positive RF (10.82+/-9.81 pg/mL);
      however, the mean synovial IL-17A levels were nearly the same. Significant
      positive correlations were found between both serum and synovial IL-17A levels
      and DAS-28 scores (r=0.556, 0.392 and p=0.001, 0.032, respectively). RA patients
      with class III functional status showed significantly higher mean serum IL-17A
      levels (17.53+/-13.43 pg/mL) than classes I and II (8.97+/-6.97 pg/mL, p=0.009).
      These led us to conclude that the elevated serum and synovial IL-17A levels in RA
      patients parallel the degree of disease activity and severity. This may highlight
      the usefulness of IL-17 (especially serum level) as a possible marker for more
      aggressive joint involvement and damage.

PMID- 21874406
TI  - Linear stability analysis of electrohydrodynamic instabilities at fluid
      interfaces in the "small feature" limit.
AB  - The endeavour to effectively harness interfacial electrohydrodynamic
      instabilities, to create small patterns, involves reducing the wavelength of the
      instability. This can be accomplished by decreasing the separation between the
      electrodes which may not always be possible. One may therefore have to reduce the
      surface tension or increase the applied voltage at a fixed electrode spacing.
      This can result in the wavelength of the pattern becoming of the same order as
      the electrode separation. Pease and Russel (J. Chem. Phys. 118, 3790 (2003)) were
      the first to argue that the commonly used Thin-Film Approximation (TFA) that
      involves an asymptotic expansion in the small parameter delta = (epsilon(0)
      phi(0)(2)/(gammah(0)))(1/2) (where epsilon (0) is the permittivity of vacuum, phi
      (0) is the root mean square value of the applied potential, gamma is the surface
      tension and h (0) is the thickness of the thin film) need not always be valid and
      gamma may not be small in experiments. Higher-order corrections to the TFA might
      therefore be necessary. We extend the Direct Current (DC) field analysis of Pease
      and Russel to an Alternating Current (AC) field. AC field has been suggested as
      an effective way of controlling the wavelength of electrohydrodynamic
      instabilities at fluid-fluid interfaces. Infact, the perfect and leaky dielectric
      limits can be realised in the same fluid at very high and very low electric field
      frequencies, respectively. Recently, Roberts and Kumar (J. Fluid Mech. 631, 255
      (2009)) carried out an analysis using TFA to investigate AC-field-induced
      instabilities at air-polymer interfaces. We propose a Generalized Model (GM),
      without the lubrication approximation, and carry out detailed comparison with the
      TFA. We consider the top fluid to be air, a perfect dielectric, and the bottom
      fluid to be a perfect or a leaky dielectric. The analysis is carried out for both
      DC and AC fields, and the deviation from TFA is expressed in terms of the
      parameter B = gammah(0)/(epsilon(0) phi(0)(2) ) = delta(-2). We discuss variation
      of the wavelength of the fastest growing mode with frequency of the applied field
      for any arbitrary value of B, unlike the analysis of Roberts and Kumar which is
      restricted to B ? 1(delta ? 1) . We also revisit the analysis of Pease and Russel
      for instabilities under DC field and present the results in terms of the single
      parameter, B.

PMID- 21874407
TI  - [Abstracts of the 39th Congress of the German Society for Rheumatology. August 31
      September 3, 2011. Munich, Germany].

PMID- 21874408
TI  - Comments on 'evaluation of a pulse oximeter sensor tester': authors' response.

PMID- 21874409
TI  - The value of laparoscopy alone or combined with hysteroscopy in the treatment of
      interstitial pregnancy: analysis of 22 cases.
AB  - OBJECTIVE: The purpose of this study was to investigate the value of laparoscopy
      alone or combined with hysteroscopy in treating clinically stable interstitial
      pregnancy. STUDY DESIGN: Clinically stable women with interstitial pregnancy were
      enrolled in the study. They were treated either with laparoscopy or with a
      combination of laparoscopy and hysteroscopy and suction. RESULTS: Of 22 cases, 15
      were treated with laparoscopy. Five out of seven cases were successfully treated
      with hysteroscopy and suction using an 8 F pediatric catheter. Two cases
      converted to a resection of the uterine cornua and salpingectomy with laparoscopy
      and laparotomy, respectively, secondary to cornual uterine perforation.
      CONCLUSION: Laparoscopy alone or combined with hysteroscopy can treat clinically
      stable interstitial pregnancy successfully. Transcervical suction using an 8 F
      pediatric catheter placed through the cornual end under laparoscopic and
      hysteroscopic guidance, preserving the uterus and fallopian tube, is an effective
      option for management of interstitial pregnancy in selected patients.

PMID- 21874410
TI  - The Great East Japan Earthquake: Tohoku University Hospital's efforts and lessons
      learned.

PMID- 21874411
TI  - Medical care issues in Japan highlighted by the regulatory approval of the da
      Vinci Surgical System.
AB  - Twelve years have passed since the emergence of the da Vinci Surgical System in
      the medical field, and highly advanced medical technology continues to develop
      rapidly. Surgeons are on a mission to provide better medical service every day.
      Yet, the Japanese Ministry of Health, Labour, and Welfare is taking a
      conservative stance against medical advancement. Two major issues that puzzle
      surgeons are the time-consuming process and delay in approval of medical devices,
      and limitations on health insurance coverage. The author of this article insists
      that now is the time to speak up for the reality that the more medical technology
      develops, the higher the costs that are necessary. He believes that all who are
      involved need to come together to share values for a better perspective.

PMID- 21874412
TI  - Advances in the surgical treatment of colorectal cancer liver metastases through
      ultrasound.
AB  - Surgery remains the gold standard of treatment for colorectal cancer liver
      metastases (CLM). The only limitation of surgery for CLM is its technical
      feasibility, the key point being to leave enough remnant liver to ensure patient
      survival. This report describes a surgical procedure based extensively on
      ultrasound guidance, which allows for curative resection in one stage and also
      for multiple bilobar CLM. This strategy minimizes the need for two-stage
      hepatectomy and may thus overcome many of the limitations and consequences of a
      two-stage approach, such as the impossibility to complete the treatment approach
      in 20%-25% of patients and the amputation of major vascular structures, which can
      result in less technical solutions for CLM relapse.

PMID- 21874413
TI  - The significance of lymph node status as a prognostic factor for esophageal
      cancer.
AB  - The revision of the TNM Classification of Malignant Tumors, 7th Edition, suggests
      the lymph node (LN) status to be the most significant risk factor in esophageal
      cancer. This article reviews the current status of LNs as indicators of
      prognosis. The significance of the number of metastatic LNs, the number of
      resected LNs, and a novel index, the "LN ratio" (metastatic LNs/removed LNs) in
      patients with esophageal cancer, were reviewed. The number of metastatic LNs
      independently predicted the prognosis of both overall survival and relapse-free
      survival. The number of positive LNs was also the best predictive marker of
      survival. Furthermore, overall survival significantly depended on the number of
      surgically removed LNs, and the LN ratio closely correlated with survival. The LN
      status is considered to be the most significant information that can be used to
      predict the prognosis. However, there are many issues that still need to be
      resolved. Better knowledge of the N-status is therefore needed to effectively
      utilize this information. Further research should focus on the N-status of
      patients with esophageal cancer.

PMID- 21874414
TI  - Topoisomerase I expression in tumors as a biological marker for CPT-11
      chemosensitivity in patients with colorectal cancer.
AB  - Irinotecan (CPT-11) is used as a first- and second-line chemotherapy for advanced
      or recurrent colorectal cancer (CRC). However, only 20%-30% of patients show an
      objective response to CPT-11 and the drug has severe toxicities, such as delayed
      onset diarrhea, neutropenia, nausea, and vomiting. It is important to select
      patients who will demonstrate sensitivity to CPT-11 treatment to avoid
      unnecessary drug toxicities and to introduce anticancer treatment benefits to CRC
      patients. DNA topoisomerase I (Topo I) is essential for vital cellular processes
      such as DNA replication, transcription, translation, recombination, and repair.
      This article reviews the possibility of assessing Topo I protein expression in
      tumors as a biological marker for CPT-11 treatment in CRC.

PMID- 21874415
TI  - Functional outcome, quality of life, and efficacy of probiotics in postoperative
      patients with colorectal cancer.
AB  - PURPOSE: We investigated the functional outcome and health-related quality of
      life (QOL) of patients who underwent a surgical resection of colorectal cancer,
      and reviewed the efficacy of probiotics for improving bowel function. METHODS: A
      questionnaire was mailed to 193 patients. Questionnaires contained the Medical
      Outcomes Study Short-Form 36-Item Health Survey and the European Organization for
      Research and Treatment of Cancer Quality of Life Questionnaire C30 as QOL scores,
      the Wexner incontinence score, and original questionnaire items about bowel
      functions. Probiotics, containing Bacillus natto and Lactobacillus acidophilus,
      were given to 77 patients for 3 months; after 3 months of treatment, the same
      questionnaire was administered. The results were analyzed by location of the
      resected cancer: rectal, colonic, right, and left. RESULTS: In the rectal group,
      defecation frequency, anal pain, and the Wexner score were significantly worse
      than in the colonic group. In the right group, the fecal form was looser and
      nighttime defecation frequency was higher than those of the left group. Three
      items in the QOL score of the right group were significantly worse compared with
      the left group. Functional outcome including defecation frequency, feeling of
      incomplete defecation, and five items in the QOL score were significantly
      improved after taking probiotics. Improvement in functional outcome and/or QOL
      was observed in all groups. CONCLUSIONS: Not only rectal resection but also
      rightside colectomy affected bowel dysfunction. Probiotics could be an effective
      treatment for improvement in functional outcome and QOL after colorectal
      resection.

PMID- 21874416
TI  - Treatment strategies for chronic expanding hematomas of the thorax.
AB  - PURPOSE: To investigate retrospectively the treatment strategies for chronic
      expanding hematoma (CEH) of the thorax. METHODS: We reviewed the medical records
      of six patients treated for CEH of the thorax at our institution between October
      1996 and October 2006. RESULTS: All of the patients had a history of thoracic
      surgery or tuberculosis with a latent period of 12-55 years before onset. One
      elderly patient with ischemic heart disease and in poor general health
      demonstrated a substantial improvement of symptoms after undergoing arterial
      embolization twice instead of surgery. The remaining five patients underwent
      either pleuropneumonectomy or a total capsule excision, following which their
      clinical condition improved remarkably. All six patients were discharged from the
      hospital. Arterial embolization was performed before surgery, and the amount of
      intraoperative bleeding ranged from 905 ml to 6,590 ml (average: 2,396 ml).
      CONCLUSION: Chronic expanding hematoma of the thorax may occur after thoracic
      surgery and a tuberculosis infection; however, considering the risk of massive
      bleeding during surgery, the decision to perform surgery should be made with
      extreme care.

PMID- 21874417
TI  - Manifestations of transthyretin-related familial amyloidotic polyneuropathy: long
      term follow-up of Japanese patients after liver transplantation.
AB  - PURPOSE: To observe which symptoms of transthyretin-related familial amyloidotic
      polyneuropathy (FAP) progressed in the long term after liver transplantation
      (LT), focusing on cardiac, kidney, and ocular symptoms. METHODS: We reviewed the
      medical records of 34 Japanese patients with FAP, who underwent LT between 1994
      and 2006. The mean follow-up period (+/- SD) after LT was 9.6 +/- 3.4 years. Of
      the 34 patients, 30 had FAP amyloidogenic transthyretin (ATTR) Val30Met, 1 had
      FAP ATTR Ser50Ile, and 3 had FAP ATTR Tyr114Cys. RESULTS: The 10-year survival
      rates from the onset of FAP and from the time of LT were 100% and 91.4%,
      respectively. Progression of ocular amyloidosis was seen in 17 (50%) patients, 13
      of whom had de novo amyloid deposits in the vitreous body; progression of cardiac
      amyloidosis was seen in 10 (29%) patients, 4 of whom had newly granular sparkling
      echo on echocardiography, and 9 of whom had newly implanted pacemakers or
      implantable cardioverter-defibrillators. Although the mean serum creatinine
      levels did not increase significantly after LT in any of the patients, the
      estimated glomerular filtration rate had decreased significantly by 7 years after
      LT. CONCLUSION: Although LT is life-saving for patients with FAP, we observed
      progression of the ocular and cardiac symptoms of FAP in a significant number of
      these patients over the long term after LT.

PMID- 21874418
TI  - Cytoreductive surgery with intraperitoneal chemotherapy to treat pseudomyxoma
      peritonei at nonspecialized hospitals.
AB  - PURPOSE: It has been reported that complete cytoreduction using peritonectomy
      combined with intraperitoneal chemotherapy improves the prognosis of patients
      with pseudomyxoma peritonei (PMP); however, this treatment strategy remains
      controversial, especially at nonspecialized institutes, because of its high
      morbidity rate. METHODS: We reviewed the clinical records of 15 consecutive
      patients with PMP, treated in nonspecialized hospitals and observed by one of us
      between 1999 and 2010. Cytoreductive surgery was done using peritonectomy
      procedures with intraperitoneal chemotherapy and was performed with curative
      intent, |in accordance with Sugarbaker. RESULTS: All patients had mucinous tumors
      disseminated in the peritoneal cavity. Complete cytoreduction was achieved in 12
      patients. Morbidity was 40% (6/15) and mortality was 0% (0/15). After a median
      follow-up period of 43 months, the 12 patients who underwent complete
      cytoreduction were disease-free with good quality of life, and 1 of the 3
      patients who underwent incomplete cytoreduction was alive with disease.
      CONCLUSIONS: These findings suggest that peritonectomy with intraperitoneal
      chemotherapy for PMP can provide prognostic benefit, even at nonspecialized
      hospitals. Considering the treatment risk, it should ideally be performed at a
      referral center, or at least by an experienced surgeon.

PMID- 21874419
TI  - Soft coagulation, polyglycolic acid felt, and fibrin glue for prevention of
      pancreatic fistula after distal pancreatectomy.
AB  - PURPOSE: To evaluate the effectiveness of using soft coagulation followed by the
      application of polyglycolic acid (PGA) felt and fibrin glue to prevent pancreatic
      fistula (PF) after distal pancreatectomy (DP). METHODS: A soft coagulation system
      was applied on the cut surface of the pancreas after ligating the main pancreatic
      duct, followed by the application of layers of PGA felt and fibrin glue on the
      layers, to prevent the development of a PF after DP. RESULTS: This technique was
      applied in nine patients, with mean drain amylase levels of 372 +/- 296, 185 +/-
      209, 54 +/- 40, and 47 +/- 34 IU/l on days 1, 3, 5, and 7, respectively, after
      DP. Only one patient (11.1%) showed a Grade A PF on day 3 after surgery; none of
      the other patients developed a fistula. CONCLUSIONS: This technique is an
      effective prophylactic measure to prevent the development of a PF after DP.

PMID- 21874420
TI  - Factors related to an early restoration of exercise capacity after major lung
      resection.
AB  - PURPOSE: We attempted to identify the factors related to an early restoration of
      the exercise capacity after lung resection. METHODS: Major lung resection was
      performed in 164 patients. Exercise testing and spirometry were performed before
      surgery, and 2 weeks and 1 month afterward. During exercise, the maximum oxygen
      uptake per minute per m(2) of body surface area (VO(2)max/m(2)) was measured. The
      percent change of VO(2)max/m(2) at 2 weeks and 1 month after surgery was
      calculated by setting the preoperative VO(2)max/m(2) value as 100%. Patients were
      then assigned to the early restoration group or late restoration group according
      to their VO(2)max/m(2) measured 2 weeks after surgery. Preoperative
      cardiopulmonary function, as well as various preoperative and intraoperative
      factors were compared between the two groups. RESULTS: At 2 weeks after surgery,
      the mean VO(2)max/m(2) was 80.9% compared with that before surgery, and was 88.1%
      at 1 month. A multivariate analysis showed that the surgical method used
      (thoracotomy and mediastinal lymph node dissection) had a significant effect on
      the postoperative restoration of the VO(2)max/m(2). CONCLUSION: An early
      restoration of exercise capacity after lung resection is possible in patients
      without mediastinal lymph node dissection and in those who have a small
      thoracotomy wound.

PMID- 21874421
TI  - Pleural defect repair with an overlapping method using fibrin glue-coated
      collagen fleece.
AB  - PURPOSE: Collagen fleece coated with fibrin glue (TachoComb; CSL Behring, Tokyo,
      Japan) is a tissue adhesive and sealant used to stop hemorrhage and air leakage.
      We assessed the efficacy of overlapping methods combined with the use of
      TachoComb to repair pleural defects. METHODS: Using a beagle animal model,
      circular and square defects were created on the pulmonary pleura and then
      repaired with TachoComb patches of varying minimum overlap widths (MOW). The
      airway pressure at which air leakage from the repaired region occurred (bursting
      pressure) was measured in a water sealing test. The ability of TachoComb to
      withstand temporal changes was assessed by repairing a 6-mm circular defect. The
      bursting pressure was measured at 5 min, 10 min, 3 h, and 24 h after the repair.
      RESULTS: TachoComb patches with an MOW >= 6 mm withstood significantly higher
      pressures than patches with an MOW <= 3 mm for both circular and square defects.
      The bursting pressure was found to increase over time for up to 3 h after being
      applied, indicating that adhesion of the TachoComb patch to the pleural tissue
      improved during the 3-h period. CONCLUSION: Pleural defects repaired using an
      overlapping method with an MOW of 6 mm were able to withstand airway pressures >=
      40 cmH(2)O.

PMID- 21874422
TI  - Cricopharyngeal myotomy for primary cricopharyngeal dysfunction caused by a
      structural abnormality localized in the cricopharyngeus muscle: report of a case.
AB  - Primary cricopharyngeal dysfunction (PCD) is a rare idiopathic disorder of the
      upper esophageal sphincter (UES), characterized by oropharyngeal dysphagia,
      frequent aspiration, and narrowing at the level of the UES. Cricopharyngeal
      myotomy (CPM) has been used to treat oropharyngeal dysphagia of different causes
      including anatomic, neuromuscular, iatrogenic, inflammatory, neoplastic, and
      idiopathic; however, the indications for CPM and predictors of its outcome are
      not clearly defined. We report a case of PCD with hypertonic UES caused by a
      structural abnormality localized in the cricopharyngeus muscle, visualized as a
      cricopharyngeal bar, which we treated successfully by CPM, achieving long-term
      relief.

PMID- 21874423
TI  - Hepatolithiasis in the hepatic hilum mimicking hilar cholangiocarcinoma: report
      of a case.
AB  - We report a rare case of hepatolithiasis, which was diagnosed as hilar
      cholangiocarcinoma and treated with hepatectomy and extrahepatic bile duct
      resection. A 59-year-old woman presented to a local hospital with liver
      dysfunction. Diagnostic imaging revealed a biliary stricture at the hepatic hilum
      and middle bile duct. Hilar cholangiocarcinoma was diagnosed, and she was
      referred to our hospital for definitive surgical treatment. She underwent left
      hepatic trisectionectomy, total caudate lobectomy, and extrahepatic bile duct
      resection. Gross examination of the resected specimen revealed intrahepatic
      stones firmly adherent to the bile duct wall. Pathological examination revealed
      no malignant lesions. The epithelium of the bile duct was absent underneath the
      stone, and the boundary between the stone and bile duct wall was ill defined. To
      our knowledge, this is the first case report of hepatolithiasis with a biliary
      stricture caused by peculiar stone formation, mimicking hilar cholangiocarcinoma.

PMID- 21874425
TI  - Local skin flap reconstruction for abdominal wound dehiscence after abdominal
      surgery with a stoma: report of two cases.
AB  - Abdominal wound dehiscence is a serious complication of laparotomy, and fascial
      dehiscence in a patient with a stoma is especially difficult to manage. We
      describe how we performed local skin flap reconstruction for abdominal wound
      dehiscence in two patients with stomas. One patient underwent sigmoidectomy with
      a colostomy for peritonitis caused by perforated diverticulitis of the sigmoid
      colon. Postoperative fascial dehiscence was repaired by rhomboid flap
      reconstruction. The other patient underwent total gastrectomy, cholecystectomy,
      and splenectomy. An ileostomy was performed for digestive tract perforation,
      which was complicated by abdominal dehiscence with necrosis of the fascia. This
      was repaired by rotation flap reconstruction. The abdominal walls in both
      patients were repaired successfully without tension.

PMID- 21874424
TI  - Pyogenic liver abscess caused by direct invasion of esophageal squamous cell
      carcinoma to the liver: report of a case.
AB  - We report a case of esophageal squamous cell carcinoma (ESCC) directly invading
      the liver and causing a pyogenic liver abscess. The patient was a 66-year-old man
      who presented with dysphagia. Esophagography, endoscopic study, and computed
      tomography (CT) showed a mass lesion in the lower third of the esophagus. A high
      fever developed on hospital day 17 and another CT scan revealed a liver abscess,
      50 * 45 mm, in the left lateral lobe of the liver. Although imaging demonstrated
      a liver abscess continuous with the tumor, we performed percutaneous transhepatic
      drainage, followed thereafter by distal esophagectomy and total gastrectomy with
      a left lateral segmental resection of the liver. The pathological findings
      confirmed a diagnosis of ESCC with direct invasion (T4N1M0, stage IVa in the TNM
      classification). The patient had an uneventful postoperative recovery.
      Microscopic examination of the resected specimen revealed the expansive growth of
      tumor cells into the hepatocellular tissues. To our knowledge, this is the first
      report of the direct invasion of esophageal cancer to the liver causing a
      pyogenic liver abscess; however, it should be borne in mind when a patient with
      esophageal cancer becomes febrile.

PMID- 21874426
TI  - Long-term survival following radical surgery after chemotherapy for
      esophagogastric adenocarcinoma with extensive lymph node metastases: report of a
      case.
AB  - A 46-year-old man was referred to us after he presented to his local physician
      complaining of difficulty eating. Upper gastrointestinal endoscopy revealed a
      tumor at the esophagogastric junction (EGJ), and moderately differentiated
      adenocarcinoma was diagnosed from the biopsy findings. Computed tomography (CT)
      showed apparent enlargement of the pretracheal lymph nodes, the lymph nodes
      around the bilateral recurrent laryngeal nerves, and the lower thoracic
      paraesophageal lymph nodes, confirming metastasis. Since the disease was far
      advanced esophagogastric cancer with marked lymph node metastases throughout the
      mediastinum, curative resection would have been unlikely. Thus, he was commenced
      on systemic chemotherapy with cisplatin (90 mg/body, day 8) + S-1 (120
      mg/body/day, given for 3 weeks, followed by a 2-week withdrawal). Even after six
      cycles of chemotherapy over 8 months, a complete response could not be achieved.
      Finally, we performed transthoracic subtotal esophagectomy with extensive lymph
      node dissection reconstructed using a gastric tube through a retrosternal route.
      The patient remains recurrence-free 7 years later.

PMID- 21874427
TI  - Curative resection of a huge malignant pancreatic endocrine tumor by
      pancreatoduodenectomy with portal and superior mesenteric vein resection and
      reconstruction using the right ovarian vein: report of a case.
AB  - Nonfunctioning pancreatic endocrine tumors (PETs) are rare and generally
      asymptomatic. A 68-year-old woman who had refused treatment for a pancreatic
      mass, revealed by ultrasonography to be 55 mm in diameter, was referred to us
      again 29 months later with jaundice. Investigations showed an 82-mm tumor in the
      head of pancreas, exposed from the papilla of Vater to the duodenal lumen. After
      biliary decompression and drainage, we performed pancreatoduodenectomy with
      resection of the portal vein and superior mesenteric vein, followed by
      reconstruction using a cylindrically customized autologous graft harvested from
      the right ovarian vein. The tumor was resected curatively. Microscopically, it
      consisted of trabecular and ribbon-like arrangement of neoplastic cells.
      Immunohistochemical staining was positive for chromogranin A and synaptophysin
      and negative for insulin, gastrin, glucagons, somatostatin, and pancreatic
      peptide. Although metastasis was detected in a lymph node along the superior
      mesenteric vein with perineural invasion, the portal and superior mesenteric
      veins had not been invaded. The diagnosis was well-differentiated nonfunctioning
      PET. The patient had an uneventful postoperative course, and there has been no
      evidence of recurrence in 12 months.

PMID- 21874428
TI  - Three-dimensional computed tomography analysis of venous collaterals between the
      middle hepatic vein tributaries and the right hepatic vein in the donor remnant
      right lobe: report of a case.
AB  - We report how three-dimensional computed tomography (3D-CT) showed the
      development of obvious venous collaterals between the middle hepatic vein (MHV)
      tributaries and the right hepatic vein (RHV) in the remnant right lobe of a donor
      liver. The donor was a healthy 34-year-old man who donated the left lobe of his
      liver with the MHV. The 3D-CT calculated that the total drainage of the MHV
      tributaries was 413 ml, corresponding to 59% of the total remnant liver. The
      congestion calculated by 3D-CT decreased from 286 ml on postoperative day (POD) 7
      to 28 ml on POD 35, corresponding to 36% and 3% of the total remnant liver,
      respectively. The donor was discharged from hospital with almost normal liver
      function, and 3D-CT analysis on POD 35 detected obvious venous collaterals
      between the MHV tributaries and the RHV. These findings suggest that
      reconstruction of the MHV tributaries in the donor remnant right lobe may not be
      necessary.

PMID- 21874429
TI  - Pelioid-type well-differentiated hepatocellular carcinoma in a patient with a
      history of taking oral contraceptives: report of a case.
AB  - We report a case of pelioid-type well-differentiated hepatocellular carcinoma
      (HCC) in a 54-year-old woman with a history of taking oral contraceptives. She
      was not infected with hepatitis viruses and her liver function test results were
      normal. Contrast-enhanced computed tomography showed an irregular-shaped and
      remarkably enhanced tumor with central necrosis. The tumor was vaguely nodular
      without capsules, and consisted of multiple pelioid cysts and sinusoidal
      dilatations with transitional forms between them. The pelioid cysts were directly
      surrounded by neoplastic cells with fatty degeneration. Since pelioid-type HCC
      has similar radiological and pathological features to peliosis hepatis, it is
      difficult to differentiate them based on drug history and imaging studies. The
      detection of stromal invasion into the portal area is necessary to distinguish
      well-differentiated HCC from benign hepatic tumors.

PMID- 21874430
TI  - Surgical removal of a denture with sharp clasps impacted in the cervicothoracic
      esophagus: report of three cases.
AB  - We report three cases of successful surgical removal of a denture with sharp
      clasps impacted in the cervical esophagus. Patient 1 was a 57-year-old woman
      institutionalized for over 30 years for schizophrenia, patient 2 was a 62-year
      old man hospitalized for brain paralysis, and patient 3 was a 64-year-old man
      suffering cerebral hemorrhage sequelae. All three patients swallowed a denture
      accidentally. Chest X-rays showed the denture with sharp clasps in the
      cervicothoracic region of the esophagus, and endoscopy revealed that it was
      lodged in the esophageal mucosa. The denture was subsequently removed by cervical
      esophagotomy. All three patients had a good clinical postoperative course without
      any complications. Thus, we recommend surgery via a cervical approach to remove a
      denture with sharp clasps impacted in the cervicothoracic esophagus, with
      intraoperative endoscopic examination for esophageal injury.

PMID- 21874431
TI  - De novo lung cancer diagnosed 32 months after liver transplantation: report of a
      case.
AB  - Patients who undergo organ transplantation are now known to be at increased risk
      of the development of de novo malignant tumors. This is primarily a consequence
      of immunosuppression, which may promote tumor development and progression by a
      variety of mechanisms. It was also reported recently that the relative ratio of
      lung tumors developing in orthotopic liver transplantation patients was 3.7 times
      greater than in the general population. We report a case of de novo lung cancer
      diagnosed in a 65-year-old man 32 months after he underwent liver transplantation
      for hepatocellular carcinoma secondary to hepatitis C virus cirrhosis. He had
      received tacrolimus as immunosuppressive therapy after the liver transplantation.
      The tumor was resected, and he remains well almost 3 years later. Previous
      reports provide evidence that immunosuppressive therapy is a risk factor for de
      novo lung cancer; thus, it is important to reduce immunosuppression for
      orthotropic liver transplantation patients, and to screen them carefully to
      detect the tumor at an early stage.

PMID- 21874432
TI  - Goblet cell carcinoid of the rectum with lymph node metastasis: report of a case.
AB  - We report an unusual case of goblet cell carcinoid (GCC) of the rectum. A 75-year
      old man was admitted to our hospital with anal bleeding, and a hard tumor was
      felt on the anterior wall of the lower rectum during rectal examination. We
      performed colonoscopy, and found a 30-mm type 2 tumor in the lower rectum and
      anal canal. Histological examination of biopsies revealed rectal adenocarcinoma.
      Based on these findings, we diagnosed rectal adenocarcinoma and performed Miles'
      operation with lymph node dissection. Histological examination revealed an
      invasive lesion composed of signet-ring-like cells. Seven regional lymph node
      metastases were seen microscopically. The tumor produced copious mucin, which was
      stained with Alcian blue. Immunohistochemistry was positive for synaptophysin,
      chromogranin A, CD56, carcinoembryonic antigen, p53, Ki-67, E-cadherin, and
      cytokeratin 20. The final diagnosis was GCC of the rectum.

PMID- 21874433
TI  - Secondary resistance of extra-gastrointestinal stromal tumors to imatinib
      mesylate: report of a case.
AB  - Extra-gastrointestinal stromal tumors (EGISTs) that do not originate in the
      digestive tract are rare. We report a case of multiple EGISTs, which was
      monitored closely by KIT gene mutation analysis and other investigations. The
      patient was a 52-year-old man in whom multiple tumors in the abdominal cavity
      were diagnosed as EGISTs. Immunohistochemical analysis revealed positive staining
      for c-kit; however, no mutations were found in the KIT gene. The tumors decreased
      in size remarkably following treatment with imatinib mesylate, but after 2 years
      of this treatment, multiple liver metastases and some regrowth of the abdominal
      masses were found simultaneously. The liver metastasis and the abdominal masses
      were excised, and further analysis of the KIT gene revealed the same mutation in
      exon 11 in the KIT gene in the metastatic tumors. We speculate that the treatment
      might have triggered development of the imatinib mesylate-resistant clone, which
      may have existed in the primary lesion as a KIT gene mutant. This report provides
      valuable insight into the mechanisms of recurrent GISTs after treatment with
      imatinib mesylate.

PMID- 21874434
TI  - Resection of lung metastases from hepatocellular carcinoma after living donor
      liver transplantation: report of two cases.
AB  - Hepatocellular carcinoma (HCC) recurrence after liver transplantation is
      associated with a poor prognosis; nonetheless, we report two cases of long-term
      survival after resection of pulmonary metastatic lesions following living donor
      liver transplantation (LDLT). The intervals between LDLT and pulmonary resection
      for the metastatic lesion were 24 months and 30 months, respectively. Regular
      checking of tumor markers and prompt workup for early detection may contribute to
      the resectability of such metastatic lesions. These cases suggest that resection
      of a solitary metastatic lesion in the lung from HCC after liver transplantation
      may be a feasible treatment for selected patients.

PMID- 21874435
TI  - Intrathoracic hernia of a retrosternal colonic graft after esophagectomy: report
      of a case.
AB  - We report a case of intrathoracic herniation of the colonic interposition pulled
      up through the retrosternal space after subtotal esophagectomy for esophageal
      cancer. The patient, a 68-year-old man, presented with progressive dysphagia
      about 1 year after this operation. We performed left thoracotomy and laparotomy,
      which revealed the reconstructed colon herniating into the left thoracic cavity
      through a large defect in the left mediastinal pleura. The redundant colon was
      resected, and the colonic graft was shortened and straightened. We concluded that
      the defect in the mediastinal pleura and colonic redundancy had permitted the
      colonic graft to herniate into the left thoracic cavity.

PMID- 21874436
TI  - Successful treatment of bronchial anastomotic stenosis with modified Dumon Y
      stent insertion in lung transplantation: report of a case.
AB  - Bronchial complications owing to airway anastomosis still remain a cause of
      morbidity and mortality following lung transplantation, and bronchial stenosis is
      the most common manifestation. Current treatment strategies include endoscopic
      balloon dilation, laser ablation, and stent insertion. Although a variety of
      stent types are currently available, it is unclear as to which type of prosthesis
      is most suitable for post-transplant bronchial complications with regard to the
      primary effects and long-term outcomes. We herein discuss a case of stenosis of
      the right bronchial anastomosis in a patient who underwent right single lung
      transplantation for idiopathic pulmonary fibrosis. This complication was
      successfully treated with the placement of a modified Dumon Y-stent. The stent
      was removed 2 months after insertion, and the patient has subsequently maintained
      an adequate airway caliber. Computed tomography, especially the sagittal section
      through the chest, is useful for detecting bronchial stenosis and monitoring the
      healing of this condition.

PMID- 21874437
TI  - Single-incision laparoscopic adrenalectomy for primary aldosteronism: report of a
      case.
AB  - We herein report the first case of a single-incision laparoscopic access (SILA)
      adrenalectomy in Japan. A 74-year-old woman who was a hepatitis B virus carrier
      was referred to our hospital because of an abnormal screening result during a
      routine health checkup. Abdominal computed tomography and an endocrinologic
      workup revealed a 2-cm left adrenal tumor with primary aldosteronism. We
      prioritized the safety of the SILA adrenalectomy by choosing a left lower
      abdominal approach. A SILS port was inserted through a 2.5-cm incision. An
      ultrasonic coagulator was the main tool used during the surgical procedure. The
      duration of the surgery was 105 min and the blood loss was 1 ml. This result was
      comparable to that of a conventional laparoscopic adrenalectomy. Based on our
      experience, an SILA adrenalectomy is thus considered to be feasible and safe,
      with better cosmetic results and a greater overall patient satisfaction than that
      of a conventional laparoscopic adrenalectomy. However, further studies will be
      necessary before the universal adoption of this new technique can be considered.

PMID- 21874438
TI  - Xanthogranulomatous pancreatitis mimicking a malignant cystic tumor of the
      pancreas: report of a case.
AB  - Xanthogranulomatous pancreatitis (XGP) is a rare inflammatory disease of the
      pancreas. A correct diagnosis is usually made only after pathological
      examination. A 76-year-old man was referred to our hospital for investigation of
      erythroderma, muscle weakness, and weight loss. We suspected dermatomyositis as a
      paraneoplastic phenomenon and investigated accordingly. Computed tomography
      showed a cystic lesion encapsulated by a thick wall in the pancreatic body. On
      magnetic resonance imaging, the lesion had low intensity on the T1-weighted
      images and heterogeneously high intensity on the T2-weighted images. (18)F
      Fluorodeoxyglucose positron emission tomography showed abnormal uptake with a
      maximum standardized uptake value of 9.1. Based on these findings, we made a
      preoperative diagnosis of intraductal papillary-mucinous carcinoma and performed
      a distal pancreatectomy. Macroscopically, the cyst was surrounded by a yellow-tan
      mass with an unclear border, and was filled with hemorrhagic and necrotic tissue.
      Microscopically, the mass contained an aggregation of many foamy histiocytes,
      lymphocytes, and plasma cells. These microscopic findings were consistent with
      xanthogranulomatous inflammation, and the lesion was diagnosed as XGP. Although
      it is a rare benign pancreatic lesion, XGP should nevertheless be considered in
      the differential diagnosis of cystic lesions of the pancreas.

PMID- 21874439
TI  - Cystic lymphangioma of the breast in an 8-year-old boy: report of a case with a
      review of the literature.
AB  - Cystic lymphangiomas are lymphatic malformations rather than true neoplasms.
      These are mainly childhood lesions. Involvement of the breast is extremely
      uncommon, and to the best of our knowledge only 17 such cases have been found in
      the literature. Breast involvement is even rarer in children, as only four of the
      reported cases are in the pediatric age group. We herein report a case of cystic
      lymphangioma of the breast in an 8-year-old male child, which was treated by
      excision. A review of the reported cases is also presented.

PMID- 21874441
TI  - Computational modeling of the skin barrier.
AB  - A simulation environment for the numerical calculation of permeation processes
      through human skin has been developed. In geometry models that represent the
      actual cell morphology of stratum corneum (SC) and deeper skin layers, the
      diffusive transport is simulated by a finite volume method. As reference elements
      for the corneocyte cells and lipid matrix, both three-dimensional
      tetrakaidecahedra and cuboids as well as two-dimensional brick-and-mortar models
      have been investigated. The central finding is that permeability and lag time of
      the different membranes can be represented in a closed form depending on model
      parameters and geometry. This allows a comparison of the models in terms of their
      barrier effectiveness at comparable cell sizes. The influence of the cell shape
      on the barrier properties has been numerically demonstrated and quantified. It is
      shown that tetrakaidecahedra in addition to an almost optimal surface-to-volume
      ratio also has a very favorable barrier-to-volume ratio. A simulation experiment
      was successfully validated with two representative test substances, the
      hydrophilic caffeine and the lipophilic flufenamic acid, which were applied in an
      aqueous vehicle with a constant dose. The input parameters for the simulation
      were determined in a companion study by experimental collaborators.

PMID- 21874440
TI  - Combined total gastrectomy, total esophagectomy, and D2 lymph node dissection
      with transverse colonic interposition for adenocarcinoma of the gastroesophageal
      junction.
AB  - The surgical treatment of adenocarcinoma of the gastroesophageal junction (GEJ)
      is complex. A large tumor involving a substantial portion of both the esophagus
      and stomach requires complete resection with negative proximal and distal margins
      as well as D2 lymph node dissection. Some investigators have found that patients
      who do not undergo radical resection have a worse prognosis; however, more
      aggressive surgical treatments are associated with increased morbidity and
      mortality. We describe our operative technique designed for complete resection of
      tumors of the GEJ. We used this technique to operate on nine patients, none of
      whom suffered anastomotic leakage or necrosis of the colonic interposition graft.

PMID- 21874442
TI  - In vitro human skin segmentation and drug concentration-skin depth profiles.
AB  - Highly optimized methods for skin segmentation are provided using tape stripping
      in combination with infrared absorption measurements for stratum corneum (SC) and
      cryosectioning for deeper skin layers. Furthermore, an example is calculated for
      demonstration of the respective procedures.

PMID- 21874443
TI  - Transcriptional regulation of epidermal barrier formation.
AB  - The mammalian epidermis is a self-renewing stratified squamous epithelium. Its
      basal cell layer contains proliferating keratinocytes that exit the cell cycle
      when they move into the suprabasal compartment. These cells activate a gene
      differentiation program aimed at building a protective epidermal barrier as they
      move toward the surface, successively going through the spinous and granular
      layers. At the completion of this process, the keratinocytes become enucleated
      and form the cornified layer, the surface layer of the skin. The highly cross
      linked protein-lipid envelope and extracellular lipids in the cornified layer
      along with cell-cell adhesions in the granular layer are required for an
      effective epidermal barrier. Transcriptional mechanisms are critical for the
      formation of the epidermal barrier, and in this chapter, we describe methods to
      evaluate the role of a transcription factor (TF) in epidermal differentiation. To
      identify direct target genes of a TF, we propose a combination of bioinformatics
      and experimental approaches. The ultimate goal of these approaches is to
      understand the mechanisms whereby a TF regulates epidermal barrier formation.

PMID- 21874444
TI  - Epidermal permeability barrier measurement in mammalian skin.
AB  - A defective skin epidermal permeability barrier (EPB) is responsible for a high
      mortality rate in premature infants and is an important risk factor in
      inflammatory skin diseases such as eczema. We report here fast and accurate
      methods for measurement of EPB in animal models or in human patients using simple
      techniques that monitor diffusion of dyes (X-Gal or Lucifer Yellow) through the
      upper epidermis and measure transepidermal water loss (TEWL) resulting from a
      defective skin barrier. Accurate diagnosis and early detection of EPB defects in
      human patients are critical for effective treatment of certain classes of
      inflammatory skin diseases.

PMID- 21874445
TI  - Assessment of permeability barriers to macromolecules in the rodent endometrium
      at the onset of implantation.
AB  - In rodents, embryo implantation is an invasive process, which begins with its
      attachment to the uterine wall and culminates in the formation of the definitive
      placenta several days later. It is critical that the endometrium provide a
      supportive environment for the implanting embryo during this process, as the
      placenta is not yet established. The concept of changing permeability barriers to
      macromolecules between different extracellular compartments in the rodent uterus
      at the onset of implantation has been established. This chapter provides
      protocols that can be used to assess this changing permeability barrier and the
      associated redistribution of macromolecules during the early phases of
      implantation in rodents. An increased permeability of the endometrial vasculature
      to plasma proteins occurs in areas adjacent to the implanting blastocyst. In
      addition, alterations in the extracellular matrix enhance the accumulation of
      fluid and extravasated macromolecules. We describe several protocols proven to be
      effective in studying and quantifying early vascular and extravascular responses
      to natural and artificial "implantation stimuli." The first three protocols
      represent qualitative and quantitative methods to assess the early endometrial
      "vascular permeability" response. On the contrary, the fourth protocol addresses
      the onset of decidualization and the arising permeability barrier, which
      restricts the movement of macromolecules through the extracellular space. This
      barrier is believed to provide transient protection for the implanting embryo
      against potentially harmful maternal serum proteins. This protocol describes
      assessment of resistance of the primary decidual zone to the movement of
      macromolecules across the compartments of the extracellular space.

PMID- 21874446
TI  - Assessment of intestinal permeability in (premature) neonates by sugar absorption
      tests.
AB  - Infants born prematurely have an enhanced intestinal permeability compared to
      healthy term infants. This enhanced permeability might be a contributing factor
      in the development of Necrotising Enterocolitis. The assessment of intestinal
      permeability in premature neonates with sugar absorption tests has been proven to
      be safe and of minimal burden to the infant. After enteral administration of a
      test solution containing lactulose and mannitol, the excretion of these sugars is
      measured in urine, and the ratio is calculated. The lactulose and mannitol
      concentrations in urine can be measured by the use of a gas chromatograph after
      pre-purification and derivatisation of the sample. Non-invasive assessment of
      intestinal permeability can be useful in monitoring the effects of experimental
      (nutritional) therapy.

PMID- 21874447
TI  - Analysis of epithelial cell shedding and gaps in the intestinal epithelium.
AB  - The intestinal barrier is formed by a monolayer of columnar epithelial cells.
      This barrier is effectively maintained despite the high turnover of epithelial
      cells in the gut. Defects in the mechanism by which barrier function is
      maintained are believed to play a central role in the pathogenesis of
      inflammatory bowel disease (IBD). Proinflammatory cytokines such as TNF-alpha and
      IFN-gamma are often elevated in inflamed tissue of patients with IBD. In fact,
      anti-TNF-alpha therapy is routinely administered to patients with Crohn's
      disease. We have previously demonstrated that intestinal epithelial cells are
      shed from the intestine leaving a 'gap' in the epithelium that is able to
      maintain barrier function. The rate of cell shedding and barrier permeability is
      substantially increased by the administration of TNF-alpha. Loss of barrier
      function at the site of a gap may provide a site of entry for disease-causing
      bacteria.

PMID- 21874448
TI  - Studying permeability in a commonly used epithelial cell line: T84 intestinal
      epithelial cells.
AB  - The integrity, or barrier function, of the intestinal epithelium is of paramount
      importance in -maintaining good health. This is largely imparted by a single
      layer of epithelial cells linked by the transmembrane tight junction protein
      complex near their apical surface. Disruption of epithelial permeability via the
      tight junctions can contribute to disease progression. The cytokine IFNgamma is
      involved in many inflammatory processes and has been shown to dramatically
      increase permeability via changes at the tight junction in experimental models.
      One of its key effectors is the transcription factor, -IRF-1. In our studies of
      the role of IRF-1 in barrier function using the human T84 intestinal epithelial
      cell monolayer model, we have found that induction of IRF-1 alone is insufficient
      to change permeability and that if IRF-1 is involved in mediating the
      permeability effects of IFNgamma, then other factors must also be required.

PMID- 21874449
TI  - Optimization of the Caco-2 permeability assay to screen drug compounds for
      intestinal absorption and efflux.
AB  - In vitro permeability assays are a valuable tool for scientists during lead
      compound optimization. As a majority of discovery projects are focused on the
      development of orally bioavailable drugs, correlation of in vitro permeability
      data to in vivo absorption results is critical for understanding the structural
      physicochemical relationship (SPR) of drugs exhibiting low levels of absorption.
      For more than a decade, the Caco-2 screening assay has remained a popular, in
      vitro system to test compounds for both intestinal permeability and efflux
      liability. Despite advances in artificial membrane technology and in silico
      modeling systems, drug compounds still benefit from testing in cell-based
      epithelial monolayer assays for lead optimization. This chapter provides
      technical information for performing and optimizing the Caco-2 assay. In
      addition, techniques are discussed for dealing with some of the most pressing
      issues surrounding in vitro permeability assays (i.e., low aqueous solubility of
      test compounds and low postassay recovery). Insights are offered to help
      researchers avoid common pitfalls in the interpretation of in vitro permeability
      data, which can often lead to the perception of misleading results for
      correlation to in vivo data.

PMID- 21874450
TI  - Ouabain modulates cell contacts as well as functions that depend on cell
      adhesion.
AB  - Ouabain, a toxic of vegetal origin used for centuries to treat heart failure, has
      recently been demonstrated to have an endogenous counterpart, most probably
      ouabain itself, which behaves as a hormone. Therefore, the challenge now is to
      discover the physiological role of hormone ouabain. We have recently shown that
      it modulates cell contacts such as gap junctions, which communicate neighboring
      cells, as well as tight junctions (TJs), which are one of the two differentiated
      features of epithelial cells, the other being apical/basolateral polarity. The
      importance of cell contacts can be hardly overestimated, since the most complex
      object in the universe, the brain, assembles itself depending on what cells
      contacts what other(s) how, when, and how is the molecular composition and
      special arrangement of the contacts involved. In the present chapter, we detail
      the protocols used to demonstrate the effect of ouabain on the molecular
      structure and functional properties of one of those cell-cell contacts: the TJ.

PMID- 21874451
TI  - Monitoring of the dynamics of epithelial dome formation using a novel culture
      chamber for long-term continuous live-cell imaging.
AB  - Epithelial tissue guarantees proper performance of many organs, e.g., the
      kidneys, the gastrointestinal organs, and endocrine glands. Epithelial layers are
      responsible for the formation and maintenance of separate compartments with
      distinct solute composition. This is achieved by epithelial layers forming a
      barrier between the two compartments and concomitantly allowing site-directed
      transepithelial transport, uptake or secretion of electrolytes, energy
      substrates, proteins, and other solutes.Research on epithelial tissue functions
      has highly profited from the establishment of tissue culture technologies
      allowing to cultivate primary epithelial cells or established epithelial cell
      lines. A property of transporting epithelia cultured in vitro that has long been
      noted is the formation of the so-called domes on solid growth supports, which
      represent fluid filled blisters between the solid growth surface and the cell
      layer. Formation of domes is regarded as a sign of active transport processes and
      an intact epithelial barrier function due to functional tight junctional cell
      cell contacts. A novel methodology for long-term live-cell light microscopy is
      described in the present article, which allows the monitoring of the dynamic
      nature of structures, such as epithelial domes over days to weeks of tissue
      culture ("under the microscope").

PMID- 21874452
TI  - Measuring permeability in human retinal epithelial cells (ARPE-19): implications
      for the study of diabetic retinopathy.
AB  - The retinal pigment epithelium (RPE) is a specialized epithelium lying in the
      interface between the -neural retina and the choriocapillaris where it forms the
      outer blood-retinal barrier (BRB). The tight junctions (TJ)s expressed in the
      outer BRB control fluids and solutes that enter the retina and this sealing
      function, which is essential for the retinal homeostasis, is impaired in diabetic
      retinopathy. In this -chapter, we provide the methods to explore the function of
      the RPE barrier by measuring Transepithelial electrical resistance (TER) and
      paracellular permeability to dextran in cultures of ARPE-19 cells (an
      immortalized RPE cell line). A method for inducing a lesion mimicking which
      occurs in diabetic retinopathy is described. In addition, methods for assessing
      mRNA expression and protein content of the main TJ proteins (occludin, zonula
      occludens-1 [ZO-1]) are detailed. Finally, we provide the methods required for
      confocal immunofluorescence detection of the TJ proteins, as well as for
      assessing the capacity of ARPE-19 cells to retain their functional properties.

PMID- 21874453
TI  - Analysis of epithelial barrier integrity in polarized lung epithelial cells.
AB  - Epithelial surfaces of the body are a key component of host defense by providing
      a mechanical barrier against potentially harmful substances. The respiratory
      tract is constantly challenged by a wide range of airborne pathogens and
      particulates, and provides not only a mucosal barrier, but also an intricate
      innate immune defense system. Disruption of the alveolar epithelial barrier can
      lead to acute lung injury, pneumonia, and acute respiratory distress syndrome.
      Protection of lung epithelial integrity, or repair of hyperpermeability with
      keratinocyte growth factor or Hsp90 inhibitors, is crucial for combating
      permeability edema. Ex vivo-differentiated lung epithelium represents a
      physiologically relevant tool for analyzing the effect of pathogens, chemicals,
      or drugs on lung barrier function. The integrity of the lung epithelial layer can
      be determined by several approaches. By combining two of these techniques,
      transepithelial electrical resistance and paracellular flux of fluorescent
      molecules, information about barrier integrity can be obtained in a prompt and
      convenient manner. As example, the virus- or bacterial toxin-mediated disruption
      of an ex vivo-differentiated mucociliary lung epithelial barrier is used here for
      assessing advantages and limitations of these methods.

PMID- 21874454
TI  - Permeability of differentiated human urothelium in vitro.
AB  - The urothelium plays a critical role in the bladder as a permeability barrier to
      urine. Whereas it was once considered a simple physical barrier, it is
      increasingly evident that urothelium has a regulatory role in maintaining the
      barrier both through self-repair and by mediating the transport of ions and small
      molecules across the transcellular and paracellular interfaces. The development
      of cell culture systems that replicate the morphological and differentiated
      features of human urothelium provides a versatile in vitro tool for exploring
      molecular and functional relationships in normal bladder physiology and for
      examining inherent changes in the urothelia of patients with dysfunctional
      bladder syndromes. In addition, it provides a useful platform to study the effect
      of pharmacological treatment on urothelial barrier function. In this review, we
      describe the development of differentiated urothelial cell constructs from in
      vitro-propagated normal human urothelial cells, and the application of methods to
      assess barrier function using transepithelial electrical resistance, water, urea,
      and dextran transport as objective and quantifiable parameters.

PMID- 21874455
TI  - Phenotyping the claudin 11 deficiency in testis: from histology to
      immunohistochemistry.
AB  - The testis is a heterogeneous organ that comprises a number of cell types,
      including germ cells at -different stages in their maturation, differentiated
      neighbor nursing cells, and endocrine somatic cells. Despite such cellular
      heterogeneity the testis is highly organized, with germ cell development and
      differentiation being compartmentalized into the interconnected tubular network
      of the seminiferous epithelium. Intratesticular scaffolds rely heavily on the
      basement membrane of the seminiferous tubules while germ cell development inside
      the seminiferous epithelium is critically dependent on the Blood Testis Barrier
      (BTB). The BTB is a macromolecular tight junction complex generated by somatic
      Sertoli cells within the seminiferous epithelium. The BTB divides the
      seminiferous epithelium into two compartments: the basal compartment, which
      delineates a niche for the proliferation and renewal of spermatogonia; and the
      adluminal compartment, where differentiating germ cells undergo meiosis and
      spermiogenesis. The BTB is unique in mammalian tissues because it is cyclically
      reconstructed during the spermatogenic cycle as preleptotene spermatocytes
      migrate from the basal compartment to the adluminal compartment and enter
      meiosis. In mouse, the loss of the BTB in the absence of the claudin 11 protein
      causes azoospermia and leads to infertility. Specifically, cldn11 deficiency
      results in sloughing of the cells of the seminiferous epithelium into the lumen.
      Understanding this pathophysiology has involved histological examination of the
      tissue defects as well as immunohistological characterization. Here, we present a
      comparative study of several modifications to the classical Hematoxylin-Eosin
      stain that may improve the diagnostic usefulness of this technique, as well as
      the use of several selective markers to identify testicular cell types.

PMID- 21874456
TI  - An in vitro system to study Sertoli cell blood-testis barrier dynamics.
AB  - The use of an in vitro system based on primary cultures of Sertoli cells isolated
      from rat testes has greatly facilitated the study of the blood-testis barrier in
      recent years. Herein, we summarize the detailed procedures on the isolation of
      undifferentiated Sertoli cells from 20-day-old rat testes, the culture of these
      cells as a monolayer on Matrigel-coated bicameral units, the characterization of
      these cultured cells, and the use of the Sertoli cell epithelium for monitoring
      the integrity of the Sertoli cell blood-testis barrier. This information is based
      on the routine use of this system in our laboratory to study the Sertoli cell
      blood-testis barrier in the past two decades, which should be helpful for
      investigators in the field.

PMID- 21874457
TI  - Analysis of endothelial barrier function in vitro.
AB  - Increased microvascular solute permeability underlies many forms of
      pathophysiological conditions, including inflammation. Endothelial monolayer
      cultures provide an excellent model system which allows systemic and mechanistic
      study of endothelial barrier function and paracellular permeability in vitro. The
      endothelial-specific complexus adherens junction protein VE-cadherin and their
      intracellular complex form pericellular structures along the cell borders which
      are critical to regulate endothelial barrier function by controlling pericellular
      permeability of vasculature. Here, we describe methods for both visualizing and
      quantifying junctional permeability and barrier changes in endothelial monolayers
      in vitro.

PMID- 21874458
TI  - Role of endothelial cell-cell junctions in endothelial permeability.
AB  - The endothelial barrier separates the inner blood compartment from the
      surrounding tissues. At the molecular level, adhesion molecules accumulate at the
      endothelial cell-cell junction and contribute to maintain vascular integrity. An
      increase in the endothelial permeability is frequently associated with the
      deregulation of junctional adhesion. Here, we review how to evaluate the in vitro
      functions of endothelial cell-cell contacts. We focus this chapter on cell
      imagery and biochemical analysis of VE-cadherin, the main constituent of adherens
      junction, and we also provide description of endothelial cell models and methods
      for studying tight junctions.

PMID- 21874459
TI  - In vitro analyses of endothelial cell permeability.
AB  - Endothelial cells lining the vessels of the vasculature and the cell-cell
      junctions, which join them, -provide the primary barrier to the passage of
      fluids, immune cells, and macromolecules between the bloodstream and the tissues.
      Appropriate and dynamic regulation of this barrier is required during normal 
      physiological processes; however, if not tightly controlled, increased
      permeability of the endothelium can also contribute to many pathological
      situations, including chronic inflammatory diseases and edema. The development of
      in vitro methods to study endothelial barrier function has been key in the
      identification of molecular mechanisms underlying many of these disease states.
      In this chapter, we describe three complementary approaches to measure
      endothelial monolayer permeability and barrier function in vitro.

PMID- 21874460
TI  - Mechano-transduction and barrier regulation in lung microvascular endothelial
      cells.
AB  - Alterations in endothelial permeability are a hallmark of inflammation as well as
      the underlying cause of many clinical syndromes. Quantifying changes in
      endothelial barrier properties to water and macromolecules can be an important
      means of assessing the degree of cellular injury and, conversely, the effect of
      therapies to attenuate the inflammatory cascade. We use a combination of an
      isolated organ system and two cell culture models to investigate mechanisms of
      endothelial barrier regulation under variety of experimental conditions. Each
      assay has its own experimental strengths and limitations and must be used
      appropriately for the questions being asked. When used collectively, they can
      provide significant insight into the molecular regulation of lung endothelial
      permeability.

PMID- 21874461
TI  - Role of caveolin-1 in the regulation of pulmonary endothelial permeability.
AB  - Endothelial permeability measurements of intact vascular beds and monolayer
      cultures are used to describe transport of small molecules (ions, water, and
      nutrients), macromolecules and plasma protein across the vascular endothelia.
      Disruption of the endothelial barrier leads to vascular hyper-permeability and
      protein-rich edema which is a key hallmark of inflammation. Transport of the most
      abundant plasma protein, albumin, occurs by means of transcellular and
      paracellular pathways. In healthy, noninflamed vessels, endothelial cell-cell
      contacts significantly restrict the paracellular permeability of albumin, whereas
      its transcellular transport from the blood to the abluminal perivascular
      interstitium occurs via caveolae. Thus, caveolae-mediated transport is a primary
      determinant of the basal endothelial permeability properties. Increased
      paracellular permeability induced during inflammation is thought to be due to the
      opening of interendothelial cell-cell junctions and disruption of endothelial
      cell-matrix contacts within the vasculature. We recently demonstrated that
      caveolae-mediated transendothelial transport (transcytosis) of macromolecules
      through the microvascular endothelial barrier is also an important mechanism
      responsible for inflammation-evoked pulmonary vascular hyperpermeability and
      protein-rich edema formation. Moreover, caveolin-1, a structural and scaffolding
      protein required for caveolae formation and transcellular transport, also plays
      an important role in oxidant-induced paracellular hyperpermeability. This review
      highlights the methods used to assess transcellular and paracellular permeability
      properties of the intact mouse lung and cultured endothelial cell monolayers.

PMID- 21874462
TI  - Assessment of endothelial permeability and leukocyte transmigration in human
      endothelial cell monolayers.
AB  - Increased vascular permeability is the hallmark of inflammation. Here, we
      describe three methods to assess vascular permeability in cell culture: (1)
      Impedance measurements of endothelial cell monolayers that allow to monitor
      changes in cell shape in real time. (2) Diffusion of fluorescently labeled
      dextran across endothelial cell monolayers to identify openings large enough for
      bulky molecules. (3) Transmigration of neutrophils through confluent endothelial
      cell monolayers to study one major process that increases endothelial
      permeability in inflammation.

PMID- 21874463
TI  - Permeability of endothelial barrier: cell culture and in vivo models.
AB  - The methods for assessment of endothelial barrier permeability are vital tools of
      experimental biology. They allow us to measure permeability of endothelial
      monolayer in cell culture and in lung vessels or to determine formation of tissue
      edema resulting from increased permeability of vasculature. This chapter provides
      an overview of the most common protocols.

PMID- 21874464
TI  - Size-selective and in vitro assessment of inner blood retina barrier
      permeability.
AB  - Assessment of tight junction integrity in vitro is fundamental when studying
      molecular processes that may be implicated in barrier dysfunction. At the blood
      brain and inner blood retina barrier (BBB and iBRB, respectively) adjacent
      endothelial cells lining the microvasculature have been shown to have very low
      rates of fluid phase transcytosis and high electrical resistances, due in part to
      the expression of tight junction proteins at the apical periphery of these cells.
      While these high electrical resistances are difficult to achieve in vitro, owing
      to complex interactions of endothelial cells in vivo with astrocytes and
      pericytes, it is possible to make an assessment of paracellular permeability when
      cells are analysed on a number of different fronts. In this regard, we will
      outline here a method for determining trans-endothelial electrical resistance,
      tracer molecule diffusion, and tight junction protein localization in primary
      cultures of bovine retinal microvascular endothelial cells. This system allows
      for the screening of a wide range of pro- and anti-angiogenic molecules in an in
      vitro model of the iBRB and can accurately assess the role individual tight
      junction proteins play in maintaining tight junction integrity in response to
      various cell stimuli.

PMID- 21874465
TI  - Assessment of permeability in barrier type of endothelium in brain using tracers:
      Evans blue, sodium fluorescein, and horseradish peroxidase.
AB  - Blood-brain barrier (BBB) constituted primarily by the capillary endothelial
      cells functions to maintain a constant environment for the brain, by preventing
      or slowing down the passage of a variety of blood-borne substances, such as serum
      proteins, chemical compounds, ions, and hormones from the circulation into the
      brain parenchyma. Various diseases such as brain tumors, epilepsy, and sepsis
      disturb the BBB integrity leading to enhanced permeability of brain microvessels.
      In animal models, a variety of experimental insults targeted to the BBB integrity
      have been shown to increase BBB permeability causing enhanced passage of
      molecules into the brain paranchyma by transcellular and/or paracellular
      pathways. This alteration can be demonstrated by intravascular infusion of
      exogenous tracers and subsequent detection of extravasated molecules in the brain
      tissue. A number of exogenous BBB tracers are available, and they can be used for
      functional and structural analysis of BBB permeability. In this chapter, we aimed
      to highlight the basic knowledge on the use of three most commonly performed
      tracers, namely Evans blue dye, sodium fluorescein, and horseradish peroxidase.
      The experimental methodologies that we use in our laboratory for the detection of
      these tracers by macroscopy, spectrophotometry, spectrophotofluorometry, and
      electron microscopy are also discussed. While tracing studies at the
      morphological level are mainly aimed at the identification and characterization
      of the tracers both in the barrier related cells and brain parenchyma,
      spectrophotometric and spectrophotofluorometric assays enable quantification of
      BBB permeability. The results of our studies that we performed using the
      mentioned tracers indicate that barrier type of endothelial cells in brain play
      an important role in paracellular and/or transcytoplasmic trafficking of
      macromolecules across BBB under various experimental settings, which may provide
      new insights in both designing approaches for the management of diseases with BBB
      breakdown and developing novel trans-BBB drug delivery strategies.

PMID- 21874466
TI  - In vitro and in vivo methods for assessing FcRn-mediated reverse transcytosis
      across the blood-brain barrier.
AB  - The neonatal Fc receptor, FcRn, mediates endocytic recycling pathway that
      prevents degradation of IgG and is expressed in most endothelial cells. The blood
      brain barrier (BBB), formed by brain endothelial cells sealed with tight
      junctions, restricts transport of IgG from the blood to the brain. In contrast,
      it has been suggested that IgG undergoes efflux from the brain parenchyma via
      reverse transcytosis across the BBB mediated by FcRn. The fast elimination of
      therapeutic antibodies from the brain via this route may limit their therapeutic
      potency. In vitro and in vivo methods described in this chapter were developed to
      facilitate research into mechanisms and dynamics of brain efflux of compounds,
      including FcRn-mediated reverse transcytosis across the BBB. The in vitro model
      uses immortalized adult rat brain endothelial cells which express high levels of
      FcRn. In vivo models use Prospective optical imaging to measure the clearance
      rate of intracerebrally injected FcRn-transported molecules tagged with near
      infrared fluorescent probes.

PMID- 21874467
TI  - Evaluation of VEGF-induced vascular permeability in mice.
AB  - Vascular endothelial growth factor (VEGF) is a potent inducer of angiogenesis and
      vascular leak involved in development, wound healing, tumor growth, macular
      degeneration, and ischemia. Studying the effects of VEGF in vitro is not always
      sufficient to approximate the complex in vivo response that involves multiple
      cell types within functioning tissues. Treating mice with an intravenous
      injection of recombinant VEGF produces a rapid and transient biochemical response
      that is accompanied by a series of ultrastructural changes. Similar events are
      induced by hypoxia-induced VEGF in the heart following myocardial infarction or
      by tumor cell-released VEGF during metastasis. Studying how intact blood vessels
      respond to VEGF will augment the further development of antipermeability
      strategies to improve disease progression in a number of pathologies.

PMID- 21874468
TI  - In vivo measurement of glioma-induced vascular permeability.
AB  - The normal blood-brain barrier (BBB) consists of tight interendothelial cell
      junctions and adjacent astrocyte end feet separated by a basal lamina surrounding
      the endothelium. The interactions between the different cell types of BBB are
      disrupted in distinct patterns in the microenvironment of glioma. Malignant
      gliomas infiltrate the surrounding normal brain parenchyma; a process associated
      with vascular permeability (VP) and breakdown of the BBB. Herein, we describe
      methods to quantitatively measure glioma-induced vascular permeability, utilizing
      an orthotopic xenograft model of glioma.

PMID- 21874469
TI  - In vivo optical imaging of ischemic blood-brain barrier disruption.
AB  - The blood-brain barrier (BBB) disruption following cerebral ischemia (stroke)
      contributes to the development of life-threatening brain edema. Recent studies
      suggested that the ischemic BBB disruption is not uniform throughout the affected
      brain region. The aim of this study was to establish in vivo optical imaging
      methods to assess the size selectivity and spatial distribution of the BBB
      disruption after a focal cerebral ischemia. The BBB permeability was assessed in
      mice subjected to a 60-min middle cerebral artery occlusion and 24 h of
      reperfusion using in vivo time domain near-infrared optical imaging after
      contrast enhancement with two tracers of different molecular size, Cy5.5 (1 kDa)
      and Cy5.5 conjugated with bovine serum albumin (BSA) (67 kDa). Volumetric
      reconstruction of contrast-enhanced brain areas in vivo and ex vivo indicated
      that the BSA-Cy5.5-enhancement is identical to the volume of infarct determined
      by TTC staining, whereas the volume of enhancement with Cy5.5 was 40% greater.
      The volume differential between areas of BBB disruption for small and large-size
      molecules could be useful for determining the size of peri-infarct tissues
      (penumbra) that can respond to neuroprotective therapies.

PMID- 21874470
TI  - Physical basics of NMR.
AB  - This chapter gives a short introduction to the physical and technical basics of
      nuclear magnetic resonance. It describes the formation of the NMR signal from the
      generation of the magnetization to the detection in the spectrometer. The
      behaviour of nuclear spins in a magnetic field is shown based on classical
      dynamics. The formation of the free induction decay and the spin echoes, as well
      as the concepts of longitudinal and transverse relaxation are explained. The
      basics of signal acquisition and reconstruction are presented. The concept of
      chemical shift is introduced with its application in NMR spectroscopy.

PMID- 21874471
TI  - Spatial encoding - basic imaging sequences.
AB  - This chapter presents the basic techniques for generating images with magnetic
      resonance. First, the usage of gradients for slice selection, frequency and phase
      encoding is explained. The concept of k-space is introduced and imperfections of
      the encoding methods are demonstrated by means of the point spread function. The
      most prominent imaging techniques based on gradient and spin echo signals are
      presented. Finally, alternative encoding procedures are described briefly.

PMID- 21874472
TI  - Basic contrast mechanisms.
AB  - This chapter provides an overview of how contrast in MR images can be achieved.
      The physical origin of the most basic contrast mechanisms is briefly explained
      and experiments to exploit these are discussed. Furthermore, the concept of using
      exogenous contrast agents is introduced.

PMID- 21874473
TI  - Scanner components.
AB  - New developments in magnetic resonance imaging (MRI) are being achieved in two
      fields: methodological and technological innovations. This chapter will focus on
      the technological aspects of scanners, explain concepts, and give hints on how to
      deal with hardware-related issues. First, magnets used in MRI and gradient units
      will be introduced. Second, the radio frequency (rf) hardware will be described
      and explained. It has an often underestimated impact on imaging quality and can
      be improved by custom-built devices if one knows how to do it.

PMID- 21874474
TI  - Small animal preparation and handling in MRI.
AB  - Animal handling and preparation is one of the most critical aspects of in vivo
      NMR imaging in small animals, and involves a broad spectrum of challenges, any of
      which could affect data quality and reproducibility. This chapter will outline
      the most critical considerations in animal handling for in vivo MRI
      experimentation in rodent models. Highly accurate and reproducible positioning is
      one of the most important aspects, since sensitivity, motion and susceptibility
      artifacts, animal imaging throughput, and ease of data quantification are all
      dependent on it. A variety of devices exist today that assist in several aspects
      of animal handling and positioning, each with its own advantages and limitations.
      This chapter will detail many of the devices that are commercially available and
      how they have dealt with integration of RF coil technology, restraint,
      anesthesia, fiducial markers, warming, and physiological monitoring. The chapter
      will additionally detail various aspects of animal anesthesia, maintenance of
      core body temperature, physiological monitoring, intubation and ventilation, and
      systemic contrast agent administration. An increasingly important factor in
      running a small animal MRI laboratory, facility biosecurity, will also be
      reviewed.

PMID- 21874475
TI  - Cerebral perfusion MRI in mice.
AB  - Perfusion MRI is a tool to assess the spatial distribution of microvascular blood
      flow. Arterial spin labeling (ASL) is shown here to be advantageous for
      quantification of cerebral microvascular blood flow (CBF) in rodents. This
      technique is today ready for assessment of a variety of murine models of human
      pathology including those associated with diffuse microvascular dysfunction. This
      chapter provides an introduction to the principles of CBF measurements by MRI
      along with a short overview over applications in which these measurements were
      found useful. The basics of commonly employed specific arterial spin-labeling
      techniques are described and theory is outlined in order to give the reader the
      ability to set up adequate post-processing tools. Three typical MR protocols for
      pulsed ASL on two different MRI systems are described in detail along with all
      necessary sequence parameters and technical requirements. The importance of the
      different parameters entering theory is discussed. Particular steps for animal
      preparation and maintenance during the experiment are given, since CBF regulation
      is sensitive to a number of experimental physiological parameters and influenced
      mainly by anesthesia and body temperature.

PMID- 21874476
TI  - High field diffusion tensor imaging in small animals and excised tissue.
AB  - Molecular diffusion plays an important role in many biological phenomena.
      Magnetic Resonance (MR) imaging is inherently sensitive to diffusion and can be
      used to help understand diffusion processes. Diffusion MR imaging is most widely
      used for imaging the ischemic brain. Diffusion imaging and diffusion tensor
      imaging (DTI) have also found clinical application in areas such as tumor
      characterization throughout the body, imaging of demyelinating disorders, and
      fiber tract mapping. DTI is also now widely used in small animal imaging-both in
      vivo and in characterizing excised tissue. DTI studies in these settings can be
      accomplished with high resolution and can offer exquisite contrast, but the
      technical and practical challenges can sometimes be different than those seen on
      clinical MRI scanners. Here, a stepwise methodology is presented for using small
      bore, high field strength scanners (>3 T) for DTI. This chapter is aimed at
      addressing readers with no prior knowledge of DTI and we present both a basic
      explanation of underlying principles and a practical approach to the experiment.

PMID- 21874477
TI  - The BOLD effect.
AB  - The purpose of this chapter is to introduce the novice NMR imager to blood oxygen
      level dependent (BOLD) contrast as well as remind the seasoned veteran of its
      beauty. Introduction to many of the factors that influence the BOLD signal is
      given higher priority than pursuing any subset in exquisite detail. Instead,
      references are given for readers seeking intense investigations into a given
      aspect. The hope is that this overview inspires the reader with the elegant
      simplicity of BOLD contrast while not, at first, intimidating too much with the
      underlying complexity. As one's knowledge of NMR matures so too will one's
      understanding, appreciation, and application of BOLD MRI. BOLD contrast derives
      from variations in the magnetic susceptibility of blood due to variations in the
      concentration of deoxyhemoglobin. These magnetic susceptibility effects produce
      local magnetic fields around blood vessels that can result in phase dispersion of
      nearby spins and, therefore, changes in signal intensity in NMR images. After
      providing brief historical context for BOLD, this chapter will follow the trail
      of magnetic susceptibility through definition, its source and location in vivo,
      and how the source and location in vivo interact with anatomical (e.g., blood
      vessel size) and imaging considerations (e.g., pulse sequence) to influence the
      BOLD signal. We will conclude by briefly highlighting clinical and preclinical
      applications using BOLD contrast.

PMID- 21874478
TI  - Screening of CEST MR contrast agents.
AB  - There has been a tremendous amount of interest in developing new MR contrast
      agents for cellular and molecular imaging applications such as the visualization
      of tumors, highlighting areas of angiogenesis, highlighting of contrast agent
      labeled therapeutic stem cells, and highlighting of contrast agent-labeled drug
      delivery vehicles. The contrast properties of paramagnetic and super-paramagnetic
      relaxation-based agents have allowed MR imaging to be used as a tool for all of
      the above applications. However, a new class of MR contrast agents, chemical
      exchange saturation transfer (CEST) agents, provides additional features such as
      (1) the ability to highlight multiple biological events at once within an image
      through the distinguishability of the different CEST contrast agents, (2) the
      ability to toggle the contrast "off-to-on" by applying a saturation pulse, and
      (3) potentially providing more information about the environment surrounding the
      contrast agent such as the pH or concentration of metabolites. In this chapter,
      we will focus on the methods which can be used in terms of acquisition schemes
      and hardware to screen these agents through MR imaging.

PMID- 21874479
TI  - Hyperpolarized noble gases as contrast agents.
AB  - Hyperpolarized noble gases ((3)He and (129)Xe) can provide NMR signal
      enhancements of 10,000 to 100,000 times that of thermally polarized gases and
      have shown great potential for applications in lung magnetic resonance imaging
      (MRI) by greatly enhancing the sensitivity and contrast. These gases obtain a
      highly polarized state by employing a spin exchange optical pumping technique. In
      this chapter, the underlying physics of spin exchange optical pumping for
      production of hyperpolarized noble gases is explained and the basic components
      and procedures for building a polarizer are described. The storage and delivery
      strategies of hyperpolarized gases for in vivo imaging are discussed. Many of the
      problems that are likely to be encountered in practical experiments and the
      corresponding detailed approaches to overcome them are also discussed.

PMID- 21874480
TI  - Hyperpolarized molecules in solution.
AB  - Hyperpolarization is a technique to enhance the nuclear polarization and thereby
      increase the available signal in magnetic resonance (MR). This chapter provides
      an introduction to the concept of hyperpolarization as well as an overview of
      dynamic nuclear polarization (DNP) and para-hydrogen induced polarization (PHIP),
      two methods used to generate hyperpolarized molecules in aqueous solution.

PMID- 21874481
TI  - MR oximetry.
AB  - MR oximetry includes methods for assessing tissue oxygenation. This chapter
      focuses on direct measurements of oxygenation. These can be divided into three
      methods. The first and most common has been termed BOLD MRI and relates to the
      quantification of deoxyhemoglobin. The second method uses an injected fluorinated
      agent which has a T (1) that is sensitive to tissue oxygen levels. The third is a
      direct measurement of T (1) under conditions where the variation in T (1) can be
      limited to that caused by changes in pO(2). These conditions can be met in the
      vitreous of the eye or the cerebrospinal fluids. Such changes in the eye have
      been called the retinal oxygenation response.

PMID- 21874482
TI  - MRI using intermolecular multiple-quantum coherences.
AB  - Intermolecular multiple-quantum coherences (iMQCs) can generate NMR signals from
      exceedingly small dipolar interactions between distant spins in solutions. In the
      last few years, these signals have been used for a wide range of applications in
      imaging and high-resolution spectroscopy. Recent applications include MRI
      contrast enhancement, suppression of inhomogeneous broadening in NMR experiments,
      and more recently, in vivo temperature measurement. In this chapter, we describe
      how basic iMQC pulse sequences work and how to select the sequence parameters to
      optimize iMQC signals and to overcome signal contamination.

PMID- 21874483
TI  - Experimental stroke research: the contributions of in vivo MRI.
AB  - Stroke is a disease that develops from the very acute time point of first
      symptoms during the next several hours and further to a chronic time period of
      days or even weeks. During this evolution process, a whole series of
      pathophysiological events takes place. Therefore, the disease is characterized by
      a continuously changing pathophysiological pattern. In consequence, as the
      disease develops over time, different imaging modalities must be chosen to
      accurately describe the status of stroke. In the present chapter, we have divided
      the evolution of stroke into various dominant steps of the cascade of events,
      with corresponding time windows. Choice of MRI variables for depiction of the
      most important aspects during these time windows are presented and their
      information content is discussed for diagnosis and for investigations into a
      better understanding of the underlying mechanisms for the disease as well as the
      relevance of these imaging tools in success assessments for therapeutic
      strategies.

PMID- 21874484
TI  - Volumetry and other quantitative measurements to assess the rodent brain.
AB  - Morphometry is defined as studying variations in and changes of shapes.
      Evaluation of shape changes in the brain is a key step in the development of new
      mouse models, the monitoring of different pathologies, and measuring
      environmental influences. Traditional morphometry was performed by manual shape
      delineation, so-called volumetry. Currently, automated methods have been
      developed that can be roughly divided into three groups: voxel-based morphometry,
      deformation-based morphometry, and shape-based morphometry. In this chapter, we
      describe the different approaches for quantitative morphometry and how they can
      be applied to the quantitative analysis of the rodent brain.

PMID- 21874485
TI  - Models of neurodegenerative disease - Alzheimer's anatomical and amyloid plaque
      imaging.
AB  - Alzheimer's disease (AD) is an important social and economic issue for our
      societies. The development of therapeutics against this severe dementia requires
      assessing the effects of new drugs in animal models thanks to dedicated
      biomarkers. According to the amyloid cascade hypothesis, beta-amyloid deposits
      are at the origin of most of the lesions associated with AD. These extracellular
      deposits are therefore one of the main targets in therapeutical strategies. Abeta
      peptides can be revealed histologically with specific dyes or antibodies, or by
      magnetic resonance microscopy (MUMRI) that uses their association with iron as a
      source of signal. The microscopic size of the lesions necessitates the
      development of specific imaging protocols. Most protocols use T (2)-weighted
      sequences that reveal the aggregates as hypointense spots. This chapter describes
      histological methods that reveal amyloid plaques with specific stains and MR
      imaging protocols for in vivo and ex vivo MR imaging of AD mice.

PMID- 21874486
TI  - MRI in animal models of psychiatric disorders.
AB  - Here we describe MRI and (1)H MRS protocols for the investigation of animal
      models (mainly mice and rats) of psychiatric disorders. The introduction provides
      general findings from brain imaging studies in patients with psychiatric diseases
      and refers to general rules regarding the use of animal models in research. The
      methods section includes a selection of basic 9.4 T MRI and MRS protocols
      applicable for the investigation of animal models of psychiatric disorders (T1W,
      T2W, FLAIR, (1)H MRS). The notes section discusses in detail a series of factors
      that can influence the outcome of the experiment: from animal handling, stress
      triggering aspects, and experimental design-related factors to technical aspects
      that affect T (1) and T (2) measurements.

PMID- 21874487
TI  - Spectroscopic imaging of the mouse brain.
AB  - Magnetic resonance spectroscopic imaging (MRSI) of the mouse brain reveals a
      wealth of metabolic information, not only from a single region of interest
      (single voxel), but spatially mapped over potentially the entire brain. However,
      MRSI requires challenging methods before the data can be obtained accurately.
      When applied in vivo, MRSI is generally combined with volume-selective spin
      perturbation to exclude artifact originating from outside the volume of interest.
      To obtain good magnetic field (B (0)) uniformity at this volume, accurate B (0)
      shimming is required. Finally, the immensely large signals originating from water
      spins need to be suppressed to prevent sidebands that contaminate the spectra, or
      even saturate the dynamic range of the MR receiver. This chapter describes
      solutions for these challenges and ends with a rationale between single-voxel MRS
      versus MRSI.

PMID- 21874488
TI  - Spinal cord - MR of rodent models.
AB  - Different MR techniques, such as relaxation times, diffusion, perfusion, and
      spectroscopy have been employed to study rodent spinal cord. In this chapter, a
      description of these methods is given, along with examples of normal metrics that
      can be derived from the MR acquisitions, as well as examples of applications to
      pathology.

PMID- 21874489
TI  - Assessment of global cardiac function.
AB  - High-resolution magnetic resonance cine imaging (cine-MRI) allows for a non
      invasive assessment of ventricular function and mass in normal mice and in
      genetically and surgically modified mouse models of cardiac disease. The
      assessment of myocardial mass and function by cine-MRI does not rely on geometric
      assumptions, as the hearts are covered from the base to the apex, typically by a
      stack of two-dimensional images. The MR data acquisition is then followed by
      image segmentation of specific cine frames in each slice to obtain geometric and
      functional parameters, such as end-diastolic volume (EDV), end-systolic volume
      (ESV) or ejection fraction (EF). This technique has been well established in
      clinical routine application and it is now also becoming the reference method in
      experimental cardiovascular MRI. The cine images are typically acquired in short-
      and long-axis orientations of the heart to facilitate an accurate assessment of
      cardiac functional parameters. These views can be difficult to identify,
      particularly in animals with diseased hearts. Furthermore, data analysis can be
      the source of a systematic error, mainly for myocardial mass measurement. We have
      established protocols that allow for a quick and reproducible way of obtaining
      the relevant cardiac views for cine-MRI, and for accurate image analysis.

PMID- 21874490
TI  - Plaque imaging in murine models of cardiovascular disease.
AB  - Comprehensive imaging of the cardiovascular system of murine models of
      atherosclerosis requires high spatial and temporal resolution as well as a high
      soft tissue contrast. High-field (>=7 T) experimental magnetic resonance imaging
      can provide noninvasive, high-resolution images of the murine cardiovascular
      system. High-field scanners, however, require special equipment and imaging
      protocols. The aim of this chapter is to provide instructions on how to obtain
      morphological and functional data on the murine cardiovascular system in animal
      models of atherosclerotic disease on a very high-field scanner (17.6 T).
      Equipment requirements are presented, and a comprehensive description of the
      methods needed to complete a magnetic resonance imaging exam, including the
      animal preparation, imaging, and image analysis are discussed. In addition,
      common problems during high-field MRI experiments and methods to validate MRI
      results are reviewed. The steps can be adopted to other MRI scanners and
      modification of the imaging parameters might allow for a more individual
      assessment of cardiovascular diseases in a number of transgenic mouse models.

PMID- 21874491
TI  - Interventional MRI in the cardiovascular system.
AB  - Endovascular stent-graft placement for thoracic aortic disease such as aortic
      dissection or aortic aneurysms is usually performed under conventional X-ray
      guidance. The experimental concept of using magnetic resonance imaging (MRI) for
      image-based guidance of vascular instruments for this specific intervention
      potentially offers a number of features that - aside from not using ionizing
      radiation - may provide added diagnostic value to the interventional therapy. It
      allows not only pre-interventional evaluation and detailed anatomic diagnosis but
      also permits immediate post-interventional, anatomical, and functional
      delineation of procedure success that may serve as a baseline for future
      comparison during follow-up.

PMID- 21874492
TI  - MR for the investigation of murine vasculature.
AB  - The investigation of alterations in vessel morphology of transgenic mouse models
      generally requires time-consuming and laborious planimetry of histological
      sections. This postmortem analysis is per se restricted to endpoint studies and,
      furthermore, may reflect the situation in vivo to a limited degree only. For the
      repetitive and noninvasive monitoring of dynamic changes in the murine
      vasculature, several protocols for high-resolution 3D MR angiography (MRA) at a
      vertical 9.4 T system are described. These protocols are based on flow
      compensated 3D gradient echo sequences with application-dependent spatial
      resolution, resulting in voxel sizes between 1 and 13 nL. To ensure constant
      physiological conditions, particular attention is paid to minimize the
      acquisition time. All measurements are carried out without a contrast agent to
      avoid temporal inconstancy of the contrast-to-noise-ratio (CNR) as well as toxic
      side effects. Moreover, metabolic alterations as a consequence of disturbed
      vascularization and blood supply are monitored by (31)P MR spectroscopy.

PMID- 21874493
TI  - MRI of the lung: non-invasive protocols and applications to small animal models
      of lung disease.
AB  - Magnetic resonance imaging (MRI) can be used in pre-clinical studies as a non
      invasive imaging tool for assessing the morphological and functional impact of
      lung diseases and for evaluating the efficacy of potential treatments for airways
      diseases. Hyperpolarized gases ((3)He or (129)Xe) MRI provides insight into the
      lung ventilation function. Lung proton MRI provides information on lung diseases
      associated with inflammatory activity or with changes in lung tissue density.
      These imaging techniques can be implemented with non-invasive protocols
      appropriate for longitudinal investigations in small animal models of lung
      diseases. This chapter will detail two (3)He and proton lung MR imaging protocols
      applied on two models of lung pathology in rodents.

PMID- 21874494
TI  - Characterization of tumor vasculature in mouse brain by USPIO contrast-enhanced
      MRI.
AB  - Detailed characterization of the tumor vasculature provides a better
      understanding of the complex mechanisms associated with tumor development and is
      especially important to evaluate responses to current therapies which target the
      tumor vasculature. Magnetic resonance imaging (MRI) studies of tumors have been
      mostly performed using gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)
      contrast-enhanced imaging, which relies on Gd-DTPA leakage from hyperpermeable
      tumor vessels and subsequent accumulation in the tumor interstitium. In certain
      tumor types, especially diffuse glioma in the brain, incorporated tumor vessels
      are not necessarily leaky, complicating effective diagnosis via Gd-DTPA contrast
      enhanced MRI. Another class of contrast agents, based on superparamagnetic
      ultrasmall iron oxide particles (USPIO), allows for non-invasive assessment of
      vascular volume within the tumor. Vascular volume can be obtained by calculating
      the change in water proton transverse relaxation rate (R (2) or R (2)) following
      USPIO administration. This allows for an objective comparison between vascular
      volumes of different tumors and also allows to perform longitudinal studies in
      order to assess, for example, treatment efficacy. Moreover, since the USPIO T (2)
      relaxivity is up to 20 times that of Gd-DTPA, USPIO provides a highly sensitive
      marker for alterations in vascular volume among tissues; this characteristic
      might be exploited for tumor detection. Thus, USPIO imaging may be a very
      attractive alternative to the most commonly used Gd-DTPA imaging and will at
      least have added value, especially for detection and delineation of diffuse
      infiltrative brain tumors.

PMID- 21874495
TI  - Cancer models-multiparametric applications of clinical MRI in rodent hepatic
      tumor model.
AB  - Small animal imaging has been a major player in an increasing amount of
      oncological experiments wherein magnetic resonance imaging (MRI) has become a
      favorite choice of measures for in vivo small animal imaging due to its
      advantages of excellent resolution and innocuousness. Based on a clinical MRI
      scanner, we propose a protocol of multiparametric MRI for noninvasive
      characterization and therapeutic evaluation of a rat model with implanted liver
      tumors. This protocol contains six sequences, namely, T (1)-weighted image
      (T1WI), T (2)-weighted image (T2WI), diffusion-weighed imaging (DWI), T (1)
      weighted dynamic contrast-enhanced MRI (DCE-MRI), T (2)-weighted dynamic
      susceptibility contrast-enhanced MRI (DSC-MRI), and contrast-enhanced T1WI (CE
      T1WI), for acquiring anatomic, diffusion, and perfusion information of tumor
      models. In this chapter, the details about this complete MRI protocol and the
      rodent liver tumor model are described in order to facilitate the readers to
      perform their own translational animal imaging research.

PMID- 21874496
TI  - BOLD MRI applied to a murine model of peripheral artery disease.
AB  - Peripheral artery disease (PAD) is the narrowing or complete occlusion of vessels
      due to the progression of atherosclerosis. Ultimately, the reduction in blood
      supply, due to a reduced lumen diameter, results in a functional deficit, e.g.,
      reduced mobility. Because function is closely tied to blood flow through large
      caliber vessels, therapeutic development to treat PAD has recently focused on
      arteriogenesis rather than angiogenesis. Optimally, the preclinical
      investigations related to such therapeutic development would take place in murine
      models of PAD to allow for future studies utilizing transgenic strains. However,
      it can be challenging to quantify functional recovery of the peripheral vascular
      network in murine models. The purpose of this work is to provide a protocol of
      temporally and spatially resolved methods for functional assessment of
      arteriogenesis in a murine model.

PMID- 21874497
TI  - Manganese-enhanced magnetic resonance imaging.
AB  - Manganese-enhanced magnetic resonance imaging (MEMRI) relies on contrasts that
      are due to the shortening of the T (1) relaxation time of tissue water protons
      that become exposed to paramagnetic manganese ions. In experimental animals, the
      technique combines the high spatial resolution achievable by MRI with the
      biological information gathered by tissue-specific or functionally induced
      accumulations of manganese. After in vivo administration, manganese ions may
      enter cells via voltage-gated calcium channels. In the nervous system, manganese
      ions are actively transported along the axon. Based on these properties, MEMRI is
      increasingly used to delineate neuroanatomical structures, assess differences in
      functional brain activity, and unravel neuronal connectivities in both healthy
      animals and models of neurological disorders. Because of the cellular toxicity of
      manganese, a major challenge for a successful MEMRI study is to achieve the
      lowest possible dose for a particular biological question. Moreover, the
      interpretation of MEMRI findings requires a profound knowledge of the behavior of
      manganese in complex organ systems under physiological and pathological
      conditions. Starting with an overview of manganese pharmacokinetics and
      mechanisms of toxicity, this chapter covers experimental methods and protocols
      for applications in neuroscience.

PMID- 21874498
TI  - Spin echo BOLD fMRI on songbirds.
AB  - The advent of high-field MRI systems has allowed implementation of BOLD fMRI on
      small animals. Increased magnetic field improves the signal-to-noise ratio and
      thus allows improvement of spatial resolution. However, it also increases
      susceptibility artefacts in the commonly acquired gradient echo images. The
      problem is particularly challenging in songbirds due to the presence of numerous
      air cavities in the skull of birds. This problem can be solved by using spin echo
      BOLD fMRI. In this chapter, we describe how to use this technique in zebra
      finches, a small songbird of 15-25 g extensively studied in behavioural
      neurosciences of birdsong. The protocol implements auditory stimuli.

PMID- 21874499
TI  - MRI to study embryonic development.
AB  - Non-invasive imaging of embryonic development has been an ultimate goal for
      embryologists for many years. Due to advances in MRI hardware and software, the
      extremely high spatial resolution necessary to study embryos can now be obtained.
      Fixed embryos can be scanned to visualize the complex 3D morphology of the
      developing embryo in great detail, sometimes referred to as MR histology. As the
      sample remains intact, it is a suitable tool for the study of rare specimens, or
      for screening of huge numbers of transgenic embryos. In vivo MRI can be used for
      time course studies of either normal development or the progression of congenital
      malformations.

PMID- 21874500
TI  - Mouse phenotyping with MRI.
AB  - The field of mouse phenotyping with magnetic resonance imaging (MRI) is rapidly
      growing, motivated by the need for improved tools for characterizing and
      evaluating mouse models of human disease. Image results can provide important
      comparisons of human conditions with mouse disease models, evaluations of
      treatment, development or disease progression, as well as direction for
      histological or other investigations. Effective mouse MRI studies require
      attention to many aspects of experiment design. In this chapter, we provide
      details and discussion of important practical considerations: hardware
      requirements, mouse handling for in vivo imaging, specimen preparation for ex
      vivo imaging, sequence and contrast agent selection, study size, and quantitative
      image analysis. We focus particularly on anatomical phenotyping, an important and
      accessible application that has shown a high potential for impact in many mouse
      models at our imaging center.

PMID- 21874501
TI  - Analysis of freshly fixed and museum invertebrate specimens using high
      resolution, high-throughput MRI.
AB  - Magnetic resonance imaging (MRI) is now considered a routine tool for comparative
      morphological imaging in small vertebrate model organisms. However, the
      application of high-resolution imaging protocols to visualize the anatomy of
      invertebrate organisms has not yet become a generally accepted tool among
      zoologists. Here, we describe MRI protocols that permit visualization of both the
      internal and the external anatomy of freshly fixed invertebrates and specimens
      from museum collections. The choice of protocols has been optimized to allow the
      assembly of the large numbers of datasets that are necessary for comparative
      morphological analyses. Although the primary focus of our work is on sea urchin
      internal anatomy, we also present results from a variety of other invertebrate
      taxa to demonstrate the principal feasibility of MRI studies to obtain anatomical
      information at high resolutions. Furthermore, we briefly describe procedures
      suitable for 3D modelling.

PMID- 21874502
TI  - Applications of hyperpolarized agents in solutions.
AB  - This chapter provides an overview of pulse sequences adapted to hyperpolarized MR
      imaging. Applications of hyperpolarized agents in aqueous solution are reviewed.
      Vascular (e.g., angiography, perfusion, and catheter tracking) as well as
      metabolic (e.g., oncology, cardiology, neurology, and pH mapping) applications
      are covered. Due to the rapid development of new applications for hyperpolarized
      agents, a review format has been used for this chapter instead of a strict
      protocol/procedure structure.

PMID- 21874503
TI  - Target-specific paramagnetic and superparamagnetic micelles for molecular MR
      imaging.
AB  - Treatment of disease can only be effective when timely and accurate diagnosis of
      the pathology is achieved. More precise diagnosis can be accomplished if the
      underlying molecular processes involved in the pathology can be imaged in vivo.
      This is the field of molecular imaging, which aims to visualize cellular function
      and molecular processes in living organisms in a non-invasive way. With that aim,
      molecular markers are specifically targeted by imaging contrast agents. Molecular
      MRI needs powerful targeted contrast agents. For that purpose, target-specific
      gadolinium-containing paramagnetic and superparamagnetic, iron oxide-based
      micelles have been developed. Micelles are lipid-based nanoparticles which are
      biocompatible and carry a high payload of MR contrast-generating agent. The
      coupling of high-affinity ligands makes the micelles target-specific.
      Additionally, this lipid-based micelle platform allows for incorporation of
      contrast generating molecules for other imaging modalities, e.g., fluorescence or
      nuclear imaging. This permits applications for multiple imaging modalities,
      making micelles a highly versatile contrast agent.

PMID- 21874504
TI  - Tracking transplanted cells by MRI - methods and protocols.
AB  - Cell tracking by magnetic resonance imaging (MRI) is an essential tool to
      understand the integration and migration of transplanted cells in vivo. At
      present, however, techniques to visualize cell transplants in patients are fairly
      limited and further development of cellular MRI is needed to advance the
      monitoring of grafted cells. The use of contrast agents to pre-label cells prior
      to transplantation is currently needed as transplanted cells integrate seamlessly
      into existing parenchyma and hence are indistinguishable from host cells. The
      development of appropriate contrast agents, as well as their in vitro
      incorporation into cells, is key to visualizing transplanted cells in vivo. We
      describe here procedures regarding how the in vitro incorporation of MR contrast
      agents can be tested, how they might affect cellular functions and how we can
      determine if sufficient contrast agent has been incorporated to allow detection.
      Before this technique can find its clinical application, in vitro and preclinical
      in vivo studies need to be conducted to determine the safety and specificity of
      this approach.

PMID- 21874505
TI  - MRI of CEST-based reporter gene.
AB  - In recent years, several reporter genes have been designed for non-invasive
      magnetic resonance imaging (MRI). Here, we offer a brief summary of recent
      advances in MRI reporter gene technology, as well as elaborated protocols for
      cloning, expression, and imaging of reporter genes based on a chemical exchange
      saturation transfer (CEST) method. These protocols emphasize new developments in
      CEST-MRI data acquisition and processing.

PMID- 21874506
TI  - NIH-DC initiative to reduce infant mortality in minority populations in
      Washington, DC: history and lessons learned.

PMID- 21874507
TI  - Clinical pathologic conference case 2: Langerhans cell histiocytosis.

PMID- 21874508
TI  - Prognostic implication of types of tumor-associated macrophages in Hodgkin
      lymphoma.
AB  - To evaluate roles of tumor-associated macrophages (TAMs) for prognosis of
      classical Hodgkin lymphoma (CHL). Expression of markers for TAMs, CD68, HLA-DR,
      CD163, HLA-DR/CD68 (M1), and CD163/CD68 (M2) was immunohistochemically examined
      in 82 cases with CHL. Positively stained cells were counted and correlation of
      number of TAMs and patients' survival time was analyzed. Number of CD163+ cells
      and M2 cells was significantly correlated with shorter overall survival (P <
      0.05), while it was marginally significant for CD68+ cells (P = 0.0827). HLA-DR +
      cells and M1 cells showed no significant correlation with overall survival. When
      confined to mixed cellularity subtype, number of M1 cells was correlated with
      favorable prognosis (P < 0.05), while M2 did not (P = 0.7). Older age and male
      sex were unfavorable factors for prognosis. At multivariate analysis, number of
      CD163+ cells, M2+ cells, and age were independent factors for poor overall
      survival (P = 0.03, 0.02, and 0.01, respectively). CD163+ cells and M2 cells
      might work to be tumor promotive in CHL. M1 cells might be tumor suppressive in
      mixed cellularity type.

PMID- 21874509
TI  - Extracellular matrix composition of the cricopharyngeus muscle.
AB  - The aim of this study was to analyze the presence and distribution of total
      collagen, type I and type III collagen, elastic fibers, fibronectin, and versican
      in the endomysium of cricopharyngeus muscles from adults of various ages. The
      study was a cross-sectional analysis of human cricopharyngeus muscles. Twenty
      seven muscles obtained from autopsies of men and women ranging in age from 28 to
      92 years were analyzed with the Picrosirius method, oxidized Weigert resorcin
      fuchsin, immunohistochemistry, and image analysis. Collagen had the highest
      density among the analyzed components. Elastic fibers surrounded each muscle
      cell; they were aligned longitudinally by their long axis and associated with
      traversing fibers, thereby forming a fiber network with embedded muscle cells.
      The fibronectin and versican contents varied widely among the specimens. We found
      no statistically significant differences between the proportion of extracellular
      matrix (ECM) components and factors such as gender and race. We conclude that the
      higher proportion of type I and type III collagen is compatible with the
      cricopharyngeus muscle's sphincteric behavior, and the arrangement of the elastic
      fibers may also contribute to the muscle's elasticity. We found no statistically
      significant correlation between the ECM components and age.

PMID- 21874511
TI  - Central venous port implantations via the cephalic vein applying an intravasal
      electrographic control of the catheter tip position: a single-center experience
      of 316 cases.
AB  - PURPOSE: The aim of this study was the analysis of the feasibility and
      complication rate of central venous port implantation with the surgical cut-down
      technique applying an intravasal electrographic control of the catheter tip
      position performed by urologists. PATIENTS AND METHODS: In the time from December
      1999 to November 2010, implantation of 324 subcutaneously implanted venous port
      systems (NuPort-System) has been performed in 316 patients, 221 men (mean age
      59.5 years, range 11-87 years) and 95 women (mean age 57.6 years, range 7-85
      years). Two hundred and fifty-nine (79.9%) port systems were placed under
      electrographic control of the catheter tip position. Duration of procedure, long
      term device function, and complications such as infections, occlusions,
      dislocations, and thrombosis were all retrospectively measured and recorded until
      removal of the device, patient's death or the last known recorded documentation.
      RESULTS: In total, 359 devices have been used in 348 surgical procedures, 324
      implantations (90.25%), and 35 explantations (9.75%). Port systems were implanted
      using the cephalic vein in 275 patients (84.9%), and in 49 (15.1%), the
      subclavian vein was used for insertion of the catheter. Mean surgical
      implantation time was 38.8 min (15-85 min). The median follow-up was 490.6 days
      (range 2-2,568); 159,764 catheter days (mean, 234 days, range 2-2,604) were
      documented. Of 35 explanted devices, the explantation was necessary due to
      complications in 28 cases (8.6%) with infection n = 6 (1.9%, 0.037 per 1,000
      catheter days), occlusion n = 8 (2.5%, 0.050 per 1,000 catheter days),
      dislocation n = 7 (2.2%, 0.044 per 1,000 catheter days), deep vein thrombosis of
      the upper extremity n = 6 (1.9%, 0.037 per 1,000 catheter days), and clotting n =
      1 (0.3%, 0.006 per 1,000 catheter days). Premature catheter removal (<30d post
      operatively) was required in 6 patients (1.9%, 0.037 per 1,000 catheter days) due
      to complications: 3 catheter dislocations/malfunctions (0.9%, 0.019 per 1,000
      catheter days), one port related infection, one pocket port infection, and one
      deep vein thrombosis of the upper extremity (0.3%, 0.006 per 1,000 catheter
      days). CONCLUSIONS: The intra-atrial ECG techniques to judge correct tip
      positioning for central venous port implantations are simple and economical. The
      exact position can be determined intraoperatively. It can justify a delayed
      postoperative chest X-ray to confirm CVC line tip placement. Nevertheless, the
      procedure and handling of the device later on has to be performed with care in
      order to avoid infections and technical problems.

PMID- 21874512
TI  - Vascular proliferation is increased in basal-like breast cancer.
AB  - Based on molecular sub-classification, basal-like breast cancer is associated
      with aggressive behavior. These tumors are frequently triple negative and lack
      traditional treatment targets. Angiogenesis, one of the hallmarks of cancer, is
      important for the local growth and spread of malignant tumors and is now a
      treatment target. The aim of this study was to explore whether angiogenesis is
      increased in relation to certain molecular subtypes of breast cancer with special
      focus on the basal-like category. Altogether, we analyzed a total of 431 breast
      cancers from two independent series after dual immunohistochemical staining of
      Factor VIII for endothelial cells and Ki-67 for proliferating cells. We then
      determined vascular proliferation in the most vascularized areas of the tumor. In
      both Series I and II, high vascular proliferation index (VPI) was significantly
      associated with expression of cytokeratin 5/6 (P = 0.001, 0.010), P-cadherin (P <
      0.0005, <0.0005), epidermal growth factor receptor (P = 0.003, 0.001), the basal
      like subtype (P = 0.001, 0.011), and the core basal phenotype (P = 0.002, 0.002),
      respectively. In Series I, high VPI was associated with the triple negative
      phenotype (P = 0.004) and p63 expression (P = 0.008). Tumor angiogenesis, as
      measured by vascular proliferation, was increased in the basal-like subtype in
      two independent breast cancer series and may thus be a possible treatment target
      in this category. Studies are required to evaluate whether this novel
      angiogenesis marker can be used to stratify patients for anti-angiogenesis
      treatment.

PMID- 21874513
TI  - Characteristics of aggressive variants in T1a renal cell carcinoma.
AB  - PURPOSE: To explore factors associated with metastasis and prognosis in T1a renal
      cell carcinoma (RCC). METHODS: We retrospectively reviewed 451 cases of sporadic
      T1aRCC among 1,060 patients admitted to the Department of Urology at Hamamatsu
      University Hospital and affiliated hospitals between 1978 and 2007.
      Clinicopathological factors were analyzed for metastatic and prognostic risks.
      RESULTS: We identified 32 RCC patients with metastatic disease, 22 with
      synchronous and 10 with metachronous metastatic RCC. Patients with metastatic
      disease had a significantly higher incidence of symptomatic cancer, as well as
      greater tumor size, C-reactive protein (CRP) level, sarcomatoid component ratio,
      histological grade 3 and microvascular invasion than those without metastasis.
      Among the 32 patients with metastasis, there is no significant difference in
      clinicopathological factors. The most common site of metastasis was bone. Among
      patients with metastatic T1aRCC, findings at diagnosis of a symptomatic cancer,
      CRP level of 0.4 mg/dL or more, tumor size of 3.0 cm or greater, histological
      grade 3, a sarcomatoid component and microvascular invasion appeared to be
      significant and independent risk factors. Significant independent risk factors
      with metachronous metastatic RCC were a symptomatic cancer and a sarcomatoid
      component at diagnosis. A CRP level of 0.4 mg/dL or more was also an independent
      prognostic factor for overall survival. CONCLUSION: RCC patients with findings at
      diagnosis of a symptomatic cancer, a sarcomatoid component and CRP level of 0.4
      mg/dL or more require intensive follow-up.

PMID- 21874514
TI  - Free nitrous acid selectively inhibits and eliminates nitrite oxidizers from
      nitrifying sequencing batch reactor.
AB  - In a complete nitrification sequencing batch reactor (CNSBR), where ammonium
      containing wastewater (200-1,000 mg N/L) is completely oxidized to nitrate up to
      2.4 kg NH(4) (+)-N/m(3) d, both ammonia oxidizers and nitrite oxidizers were
      enriched in the sludge granules. Quantitative fluorescence in situ hybridization
      analyses of the sludge granules of the CNSBR showed that ammonia oxidizers and
      nitrite oxidizers occupied 31 and 4.2% of total bacteria, respectively. Most of
      the nitrite oxidizers were Nitrobacter species (95% of the nitrite oxidizers) and
      the remainder was Nitrospira species. The population of nitrite oxidizers was
      significantly higher than that of partial nitrification SBR (PNSBR) where most of
      the ammonium was oxidized to nitrite. The PNSBR had 37% (ammonia oxidizers) and
      0.4% (nitrite oxidizers) of total bacteria. Comparative study with CNSBR and
      PNSBR revealed that free nitrous acid, rather than free ammonia, played a
      critical inhibition role to wash out nitrite oxidizers from the reactor. The
      concentrations of free ammonia and nitrite as well as free nitrous acid in the
      CNSBR selected Nitrobacter as the dominant nitrite oxidizers rather than
      Nitrospira.

PMID- 21874515
TI  - Social referencing in dog-owner dyads?
AB  - Social referencing is the seeking of information from another individual to form
      one's own understanding and guide action. In this study, adult dogs were tested
      in a social referencing paradigm involving their owner and a potentially scary
      object. Dogs received either a positive or negative message from the owner. The
      aim was to evaluate the presence of referential looking to the owner, behavioural
      regulation based on the owner's (vocal and facial) emotional message and
      observational conditioning following the owner's actions towards the object. Most
      dogs (83%) looked referentially to the owner after looking at the strange object,
      thus they appear to seek information about the environment from the human, but
      little differences were found between dogs in the positive and negative groups as
      regards behavioural regulation: possible explanations for this are discussed.
      Finally, a strong effect of observational conditioning was found with dogs in the
      positive group moving closer to the fan and dogs in the negative group moving
      away, both mirroring their owner's behaviour. Results are discussed in relation
      to studies on human-dog communication, attachment and social learning.

PMID- 21874517
TI  - Callose deposition in the phloem plasmodesmata and inhibition of phloem transport
      in citrus leaves infected with "Candidatus Liberibacter asiaticus".
AB  - Huanglongbing (HLB) is a destructive disease of citrus trees caused by phloem
      limited bacteria, Candidatus Liberibacter spp. One of the early microscopic
      manifestations of HLB is excessive starch accumulation in leaf chloroplasts. We
      hypothesize that the causative bacteria in the phloem may intervene
      photoassimilate export, causing the starch to over-accumulate. We examined citrus
      leaf phloem cells by microscopy methods to characterize plant responses to
      Liberibacter infection and the contribution of these responses to the
      pathogenicity of HLB. Plasmodesmata pore units (PPUs) connecting companion cells
      and sieve elements were stained with a callose-specific dye in the Liberibacter
      infected leaf phloem cells; callose accumulated around PPUs before starch began
      to accumulate in the chloroplasts. When examined by transmission electron
      microscopy, PPUs with abnormally large callose deposits were more abundant in the
      Liberibacter-infected samples than in the uninfected samples. We demonstrated an
      impairment of symplastic dye movement into the vascular tissue and delayed
      photoassimilate export in the Liberibacter-infected leaves. Liberibacter
      infection was also linked to callose deposition in the sieve plates, which
      effectively reduced the sizes of sieve pores. Our results indicate that
      Liberibacter infection is accompanied by callose deposition in PPUs and sieve
      pores of the sieve tubes and suggest that the phloem plugging by callose inhibits
      phloem transport, contributing to the development of HLB symptoms.

PMID- 21874519
TI  - The biliopancreatic diversion with a duodenal switch (BPDDS): how is it optimally
      performed?
AB  - BACKGROUND: The biliopancreatic diversion with duodenal switch can be performed
      by different combinations of restriction and malabsorption. The aim of this study
      was to evaluate weight loss and potential side effects for two variants of the
      procedure. METHODS: All patients eligible for a 2-year follow-up (n = 182) was
      included in the study. Thirty-five patients (group A) had a gastric remnant with
      a volume of approximately 200 ml, an alimentary limb (AL) of 250 cm, and a common
      channel (CC) of 100 cm, while 147 patients (group B) had a gastric remnant of 100
      120 ml, an AL of 40%, and a CC of 10% of the small bowel length. Preoperative
      variables, such as body mass index (BMI), sex, age, and factors that might
      influence weight loss, and postoperative weight loss and side effects were
      registered and compared. RESULTS: Preoperatively, the BMI was 50.6 in group A and
      52.1 in group B (ns), with no difference in age, sex, or variables that might
      influence weight loss. At 2 years, the BMI was 33.1 in group A (n = 34) and 28.5
      in group B (n = 119) with an adjusted difference in weight loss of 5.6 BMI units
      between the groups (p < 0.001). Vitamin D status was also better in group B than
      in group A at follow-up, while there was no difference in side effects.
      CONCLUSIONS: Patients with a remnant stomach of 100-120 ml, and AL and CC with
      individually adapted lengths had a larger weight loss and better vitamin D status
      postoperatively without an increase in side effects.

PMID- 21874516
TI  - Exploration for the salt stress tolerance genes from a salt-treated halophyte,
      Suaeda asparagoides.
AB  - Salinity stress severely affects plant growth and development causing crop loss
      worldwide. Suaeda asparagoides is a salt-marsh euhalophyte widely distributed in
      southwestern foreshore of Korea. To isolate salt tolerance genes from S.
      asparagoides, we constructed a cDNA library from leaf tissues of S. asparagoides
      that was treated with 200 mM NaCl. A total of 1,056 clones were randomly selected
      for EST sequencing, and 932 of them produced readable sequence. By sequence
      analysis, we identified 538 unigenes and registered each in National Center for
      Biotechnology Information. The 80 salt stress related genes were selected to
      study their differential expression. Reverse transcription-PCR and Northern blot
      analysis revealed that 23 genes were differentially expressed under the high
      salinity stress conditions in S. asparagoides. They are functionally diverse
      including transport, signal transduction, transcription factor, metabolism and
      stress associated protein, and unknown function. Among them dehydrin (SaDhn) and
      RNA binding protein (SaRBP1) were examined for their abiotic stress tolerance in
      yeast (Saccharomyces cerevisiae). Yeast overexpressing SaDhn and SaRBP1 showed
      enhanced tolerance to osmotic, freezing and heat shock stresses. This study
      provides the evidence that SaRBP1 and SaDhn from S. asparagoides exert abiotic
      stress tolerance in yeast. Information of salt stress related genes from S.
      asparagoides would contribute for the accumulating genetic resources to improve
      osmotic tolerance in plants.

PMID- 21874520
TI  - Molecular characterization of two genotypes of a new polerovirus infecting
      brassicas in China.
AB  - The genomic RNA sequences of two genotypes of a brassica-infecting polerovirus
      from China were determined. Sequence analysis revealed that the virus was closely
      related to but significantly different from turnip yellows virus (TuYV). This
      virus and other poleroviruses, including TuYV, had less than 90% amino acid
      sequence identity in all gene products except the coat protein. Based on the
      molecular criterion (>10% amino acid sequence difference) for species demarcation
      in the genus Polerovirus, the virus represents a distinct species for which the
      name Brassica yellows virus (BrYV) is proposed. Interestingly, there were two
      genotypes of BrYV, which mainly differed in the 5'-terminal half of the genome.

PMID- 21874521
TI  - Seroprevalence and molecular detection of hepatitis E virus in Yunnan Province,
      China.
AB  - In this study, the prevalence and characteristics of hepatitis E virus (HEV) in
      pigs and the general population in the Yunnan province, China, were evaluated.
      Nine hundred sixty sera, 95 liver and 60 feces samples were randomly collected
      from pig farms and abattoirs, in addition 173 human sera were sampled in the
      provincial capital city for a serological survey and an RT-nPCR assay. The
      screening results showed that among 621 samples collected from five pig farms,
      the HEV-specific IgG positive rate ranged from 73.2% to 83.5%, and the overall
      seroprevalence was 78.9% (490/621). A further analysis revealed that the
      seroprevalence increased with age. The positive rate of human serum samples was
      39.9% (69/173). HEV RNA was detected in five swine feces, six swine liver and one
      anti-HEV-IgM-positive human serum sample by RT-nPCR. Sequence and alignment of
      the 348-nt PCR-amplified products of 12 HEV strains identified nine distinct
      nucleotide sequences. Phylogenetic and molecular evolutionary analysis revealed
      that these nine sequences shared 84.2% to 100.0% nucleotide sequence identity
      with each other, with all isolates belonging to genotype 4 HEV and clustering
      with other Chinese swine and human HEV sequences determined earlier. This study
      results suggest that the prevalence of genotype 4 HEV is serious, both in pig
      herds and in the human population, and authorities should pay more attention to
      the prevalence of HEV in southwest China.

PMID- 21874522
TI  - Uranium carcinogenicity in humans might depend on the physical and chemical
      nature of uranium and its isotopic composition: results from pilot
      epidemiological study of French nuclear workers.
AB  - OBJECTIVE: To study the cancer risk related to protracted, low-dose exposure to
      different industrial uranium compounds, paying attention to their isotopic
      composition and solubility. METHODS: Two thousand and ninety-seven workers
      employed at the AREVA NC uranium processing plant (France) were followed up for
      mortality from 1960 to 2006. Historical exposure to uranium and other
      carcinogenic chemical and physical pollutants was assessed on the basis of the
      plant-specific job-exposure matrix. For each type of uranium, Cox regression
      models stratified on sex and calendar period, and adjusted for socioeconomic
      status and potentially confounding co-exposures were used to estimate hazard
      ratios (HRs) for mortality from lung cancer (53 deaths) and lymphatic and
      hematopoietic tissue malignancies (21 deaths). RESULTS: We observed that exposure
      to reprocessed uranium entails increasing risks of mortality from lung cancer and
      lymphatic and hematopoietic malignancies (the most significant HR being
      respectively 1.14 (95% CI: 1.00-1.31) and 1.20 (95% CI: 1.01-1.43) per unit of a
      time-lagged log-transformed continuous exposure scores), and that the HRs tend to
      increase with decreasing solubility of the compounds. CONCLUSION: Our results
      suggest that uranium carcinogenicity may depend on isotopic composition and
      solubility of uranium compounds. This study is the first to show the carcinogenic
      effect of slowly soluble reprocessed uranium on two uranium target organs. This
      finding is consistent with data from epidemiological and experimental studies on
      similar compounds but need to be confirmed in the more powerful dose-response
      analysis.

PMID- 21874523
TI  - A Phororhacoid bird from the Eocene of Africa.
AB  - The bird fossil record is globally scarce in Africa. The early Tertiary evolution
      of terrestrial birds is virtually unknown in that continent. Here, we report on a
      femur of a large terrestrial new genus discovered from the early or early middle
      Eocene (between ~52 and 46 Ma) of south-western Algeria. This femur shows all the
      morphological features of the Phororhacoidea, the so-called Terror Birds. Most of
      the phororhacoids were indeed large, or even gigantic, flightless predators or
      scavengers with no close modern analogs. It is likely that this extinct group
      originated in South America, where they are known from the late Paleocene to the
      late Pleistocene (~59 to 0.01 Ma). The presence of a phororhacoid bird in Africa
      cannot be explained by a vicariant mechanism because these birds first appeared
      in South America well after the onset of the mid-Cretaceous Gondwana break up
      (~100 million years old). Here, we propose two hypotheses to account for this
      occurrence, either an early dispersal of small members of this group, which were
      still able of a limited flight, or a transoceanic migration of flightless birds
      from South America to Africa during the Paleocene or earliest Eocene.
      Paleogeographic reconstructions of the South Atlantic Ocean suggest the existence
      of several islands of considerable size between South America and Africa during
      the early Tertiary, which could have helped a transatlantic dispersal of
      phororhacoids.

PMID- 21874524
TI  - Latent variable model for suicide risk in relation to social capital and socio
      economic status.
AB  - BACKGROUND: There is little evidence on the association between suicide outcomes
      (ideation, attempts, self-harm) and social capital. This paper investigates such
      associations using a structural equation model based on health survey data, and
      allowing for both individual and contextual risk factors. METHODS: Social capital
      and other major risk factors for suicide, namely socioeconomic status and social
      isolation, are modelled as latent variables that are proxied (or measured) by
      observed indicators or question responses for survey subjects. These latent
      scales predict suicide risk in the structural component of the model. Also
      relevant to explaining suicide risk are contextual variables, such as area
      deprivation and region of residence, as well as the subject's demographic status.
      The analysis is based on the 2007 Adult Psychiatric Morbidity Survey and includes
      7,403 English subjects. A Bayesian modelling strategy is used. RESULTS: Models
      with and without social capital as a predictor of suicide risk are applied. A
      benefit to statistical fit is demonstrated when social capital is added as a
      predictor. Social capital varies significantly by geographic context variables
      (neighbourhood deprivation, region), and this impacts on the direct effects of
      these contextual variables on suicide risk. In particular, area deprivation is
      not confirmed as a distinct significant influence. The model develops a
      suicidality risk score incorporating social capital, and the success of this risk
      score in predicting actual suicide events is demonstrated. CONCLUSIONS: Social
      capital as reflected in neighbourhood perceptions is a significant factor
      affecting risks of different types of self-harm and may mediate the effects of
      other contextual variables such as area deprivation.

PMID- 21874526
TI  - Communitarian bioethics: Preface.

PMID- 21874525
TI  - Probiotics decreased the bioavailability of the bile acid analog, monoketocholic
      acid, when coadministered with gliclazide, in healthy but not diabetic rats.
AB  - In recent studies we showed that gliclazide has no hypoglycemic effect on type 1
      diabetic (T1D) rats while MKC does, and their combination exerted a better
      hypoglycemic effect than MKC alone. We also showed that the most hypoglycemic
      effect was noticed when T1D rats were treated with probiotics then gavaged with
      MKC + gliclazide (blood glucose decreased from 24 +/- 3 to 10 +/- 2 mmol/l). The
      aim of this study is to investigate the influence of probiotics on MKC
      pharmacokinetics when coadministered with gliclazide, in T1D rats. 80 male Wistar
      rats (weight 350 +/- 50 g) were randomly allocated into 8 groups (10 rats/group),
      4 of which were injected with alloxan (30 mg/kg) to induce T1D. Group 1 was
      healthy and group 2 was diabetic. Groups 3 (healthy) and 4 (diabetic) were
      gavaged with probiotics (75 mg/kg) every 12 h for 3 days and 12 h later all
      groups received a single oral dose of MKC + gliclazide (4 and 20 mg/kg
      respectively). The remaining 4 groups were treated in the same way but
      administered MKC + gliclazide via the i.v. route. Blood samples collected from
      T1D rats prior to MKC + gliclazide revealed that probiotic treatment alone
      reduced blood glucose levels twofold. When coadministered with gliclazide, the
      bioavailability of MKC was reduced in healthy rats treated with probiotics but
      remained the same in diabetic pretreated rats. The decrease in MKC
      bioavailability, when administered with gliclazide, caused by probiotic treatment
      in healthy but not diabetic rats suggests that probiotic treatment induced MKC
      metabolism or impaired its absorption, only in healthy animals. The different MKC
      bioavailability in healthy and diabetic rats could be explained by different
      induction of presystemic elimination of MKC in the gut by probiotic treatment.

PMID- 21874527
TI  - Arsenic trioxide versus tetraarsenic oxide in biomedical research:
      misunderstandings and misinterpretations.
AB  - This work presents an analytical chemist's view on the sometimes unconscious use
      of arsenic trioxide in (bio)medical research. Arsenic trioxide is a frequently
      used chemical in cancer treatment research and its action to various malignant
      cells has been extensively studied and published. Unfortunately some research
      articles show trivial errors with regards to background knowledge of the
      chemical, handling the chemical, experimental design and interpretation of
      results like e.g. in a range of articles comparing advantages of tetraarsenic
      oxide over arsenic trioxide (dimeric/monomeric) although the dissolution of both
      yields the same active compound (HAsO(2)). To fully understand the implications
      of these errors we will highlight some of them with the intent to harmonize
      future work in this field.

PMID- 21874528
TI  - Differential pulmonary transcriptomic profiles in murine lungs infected with low
      and highly virulent influenza H3N2 viruses reveal dysregulation of TREM1
      signaling, cytokines, and chemokines.
AB  - Investigating the relationships between critical influenza viral mutations
      contributing to increased virulence and host expression factors will shed light
      on the process of severe pathogenesis from the systems biology perspective. We
      previously generated a mouse-adapted, highly virulent influenza (HVI) virus
      through serial lung-to-lung passaging of a human influenza H3N2 virus strain that
      causes low virulent influenza (LVI) in murine lungs. This HVI virus is
      characterized by enhanced replication kinetics, severe lung injury, and systemic
      spread to major organs. Our gene microarray investigations compared the host
      transcriptomic responses of murine lungs to LVI virus and its HVI descendant at
      12, 48, and 96 h following infection. More intense expression of genes associated
      with cytokine activity, type 1 interferon response, and apoptosis was evident in
      HVI at all time-points. We highlighted dysregulation of the TREM1 signaling
      pathway (an amplifier of cytokine production) that is likely to be upregulated in
      infiltrating neutrophils in HVI-infected lungs. The cytokine gene expression
      changes were corroborated by elevated levels of multiple cytokine and chemokine
      proteins in the bronchoalveolar lavage fluid of infected mice, especially at 12 h
      post-infection. Concomitantly, the downregulation of genes that mediate
      proliferative, developmental, and metabolic processes likely contributed to the
      lethality of HVI as well as lack of lung repair. Overall, our comparative
      transcriptomic study provided insights into key host factors that influence the
      dynamics, pathogenesis, and outcome of severe influenza.

PMID- 21874529
TI  - Chemiluminescent reductive acridinium triggering (CRAT)--mechanism and
      applications.
AB  - Acridinium esters traditionally are triggered using basic hydrogen peroxide. By
      serendipity, we have found that acridinium esters can also be triggered with
      emission of chemiluminescence by reductive triggering, e.g., by zinc metal or
      reduced forms of ferric and cupric salts. Furthermore, organic reducing compounds
      like dithiothreitol, tricarboxyethylphosphine or glutathione could be used in
      combination with organic oxidants like quinones or inorganic ferric or cupric
      salts. Mechanisms are proposed which involve the intermediacy of superoxide. Two
      forms of reactive oxygen species (i.e., hydrogen peroxide and superoxide) could
      be discriminated based on differences in kinetics. Some applications (improved
      detection of acridinium ester, use of acridinium ester as redox probes) are
      discussed.

PMID- 21874530
TI  - Development and validation of a reference measurement procedure for certification
      of phenytoin, phenobarbital, lamotrigine, and topiramate in human serum using
      isotope-dilution liquid chromatography/tandem mass spectrometry.
AB  - Phenytoin (PHT), phenobarbital (PHB), lamotrigine (LTG), and topiramate (TPM) are
      some of the most widely used antiepileptic drugs (AEDs). Monitoring of their
      concentrations in serum is important for the treatment of epilepsy. A reference
      measurement procedure (RMP) for certification of PHT, PHB, LTG, and TPM in serum
      has been developed and critically evaluated. Isotopically labeled compounds of
      PHT, PHB, LTG, and TPM are used as internal standards for the four AEDs. The four
      drugs and their respective labeled internal standards are simultaneously
      extracted from serum using solid-phase extraction prior to reversed-phase liquid
      chromatography-tandem mass spectrometry (LC-MS/MS). Chromatographic separation
      was performed using a C(18) column. Electrospray ionization (ESI) in the positive
      ion mode for PHT and LTG, and in the negative ion mode for PHB and TPM were used.
      The recovery of AEDs added to serum (accuracy of the extraction method) was
      evaluated by recovery studies of measuring the four drugs in spiked samples with
      known drug levels. The recoveries of the added drugs ranged from 98.6% to 102.0%.
      The absolute recoveries (extraction efficiencies) of the four drugs with this
      method ranged from 97% to 100%. Excellent repeatability was obtained for the four
      drugs with between-set coefficients of variation (CVs) within 1%. The type B
      components estimates are conservatively large and are considerably larger than
      the type A component. Therefore, we use the usual metrological expansion factor
      of 2 to provide an approximate 95% coverage interval. The relative expanded
      uncertainties for the four AEDs ranged from 2.3% to 2.4%. This LC-MS/MS RMP for
      PHT, PHB, LTG, and TPM in serum demonstrating good accuracy and precision can be
      used to assess the accuracy of routine methods used in clinical laboratories.

PMID- 21874531
TI  - Arginine and polyamines in Helicobacter pylori-induced immune dysregulation and
      gastric carcinogenesis.
AB  - L-arginine (L-Arg) is metabolized by nitric oxide synthase and arginase enzymes.
      The gastric pathogen Helicobacter pylori causes peptic ulcer disease and gastric
      cancer. We have shown that alterations in L-Arg availability and metabolism into
      polyamines contribute significantly to the dysregulation of the host immune
      response to this infection. Nitric oxide (NO) derived from inducible NO synthase
      (iNOS) can kill H. pylori. There are multiple mechanisms leading to failure of
      this process, including competition for L-Arg substrate by H. pylori arginase,
      and induction of host macrophage arginase II (Arg2) and ornithine decarboxylase
      (ODC). Generation of spermine by ODC inhibits iNOS translation and NO-mediated H.
      pylori killing. Expression of ODC is dependent on formation of a unique AP-1
      complex, leading to upregulation of c-Myc as a transcriptional enhancer.
      Macrophage apoptosis is mediated by oxidation of spermine via the enzyme spermine
      oxidase (SMO) that generates hydrogen peroxide (H(2)O(2)), and thus oxidative
      stress-induced mitochondrial membrane polarization. Our studies have demonstrated
      that apoptosis occurs through a pERK -> pc-Fos/c-Jun -> c-Myc -> ODC -> SMO
      pathway. In gastric epithelial cells, activation of oxidative stress by H. pylori
      is dependent on SMO induction and results in both apoptosis and DNA damage, such
      that inhibition or knockdown of SMO markedly attenuates these events. In summary,
      L-Arg metabolism by the arginase-ODC pathway and the activation of SMO leads to
      H. pylori-induced DNA damage and immune dysregulation through polyamine-mediated
      oxidative stress and impairment of antimicrobial NO synthesis. Our studies
      indicate novel targets for therapeutic intervention in H. pylori-associated
      diseases, including gastritis, ulcer disease, and gastric cancer.

PMID- 21874532
TI  - Polyamine catabolism: target for antiproliferative therapies in animals and
      stress tolerance strategies in plants.
AB  - Metabolism of polyamines spermidine and spermine, and their diamine precursor,
      putrescine, has been a target for antineoplastic therapy since these naturally
      occurring alkyl amines were found essential for normal mammalian cell growth.
      Intracellular polyamine concentrations are maintained at a cell type-specific set
      point through the coordinated and highly regulated interplay between
      biosynthesis, transport, and catabolism. A correlation between regulation of cell
      proliferation and polyamine metabolism is described. In particular, polyamine
      catabolism involves copper-containing amine oxidases and FAD-dependent polyamine
      oxidases. Several studies showed an important role of these enzymes in several
      developmental and disease-related processes in both animals and plants through a
      control on polyamine homeostasis in response to normal cellular signals, drug
      treatment, environmental and/or cellular stressors. The production of toxic
      aldehydes and reactive oxygen species, H(2)O(2) in particular, by these oxidases
      using extracellular and intracellular polyamines as substrates, suggests a
      mechanism by which the oxidases can be exploited as antineoplastic drug targets.
      This minireview summarizes recent advances on the physiological roles of
      polyamine catabolism in animals and plants in an attempt to highlight differences
      and similarities that may contribute to determine in detail the underlined
      mechanisms involved. This information could be useful in evaluating the
      possibility of this metabolic pathway as a target for new antiproliferative
      therapies in animals and stress tolerance strategies in plants.

PMID- 21874534
TI  - Microsatellite based analysis of genetic diversity of popular black pepper
      genotypes in South India.
AB  - The genotypes of black pepper are morphologically and genotypically highly
      diverse and carry all the cumulative variations inherited and maintained through
      generations. The present study describes the Simple Sequence Repeat (SSR) or
      microsatellite based assessment of genetic diversity among forty popular
      genotypes and four different species of black pepper in Southern region of India.
      For isolation of SSR primers, our earlier attempts with enrichment strategies
      like 'Triplex affinity capture' did not extract a single SSR primer due to close
      proximity of restriction sites to the SSR motif. Hence we developed a 'Sequential
      Reverse Genome Walking (SRGW)' strategy with better enrichment efficiency of 72%
      that generated seven new SSR primers. Genotyping precisely discriminated majority
      of genotypes which indicated that the SSR primers are very informative. A total
      of 62 alleles with an average of 15.5 alleles over 4 loci were identified. All
      the SSR primers showed an average Polymorphism Information Content (PIC) value of
      0.85. The estimated average Shared Allele Frequency ranged between 1.57 and
      20.12%. The PCA plot revealed four closely related individual groups and
      identified Karimunda, Wild pepper and a local landrace 'local b' as the most
      divergent genotypes. Cluster analysis exposed the genetic relatedness between
      hybrids and selections with other known cultivars. The introduction of black
      pepper from South India to Malaysia was emphasized from the observation of
      genetic similarity of Malaysian cultivar 'Kuching' with other indigenous popular
      cultivars. The study was first to portray the precise genetic relatedness among
      the major indigenous genotypes of black pepper.

PMID- 21874535
TI  - Intragenomic bet-hedging.
AB  - The notion of intragenomic bet-hedging is introduced by modeling a system where
      one locus is seen as setting the "environment" for selection in a two-locus
      genetic system. Using a spatially structured simulation model I show that bet
      hedging alleles with a lower mean fitness and lower variance of fitness across
      genotypes at a different locus can go to fixation, potentially providing a
      mechanism for the reduction of severe heterozygote advantage.

PMID- 21874533
TI  - Regulation of survival gene hsp70.
AB  - Rapid expression of the survival gene, inducible heat shock protein 70 (hsp70),
      is critical for mounting cytoprotection against severe cellular stress, like
      elevated temperature. Hsp70 protein chaperones the refolding of heat-denatured
      peptides to minimize proteolytic degradation as a part of an eukaryotically
      conserved phenomenon referred to as the heat shock response. The physiologic
      stress associated with exercise, which can include elevated temperature,
      mechanical damage, hypoxia, lowered pH, and reactive oxygen species generation,
      may promote protein unfolding, leading to hsp70 gene expression in skeletal
      myofibers. Although the pre-transcriptional activation of hsp70 gene expression
      has been thoroughly reviewed, discussion of downstream hsp70 gene regulation is
      less extensive. The purpose of this brief review was to examine all levels of
      hsp70 gene regulation in response to heat stress and exercise with a special
      focus on skeletal myofibers where data are available. In general, while heat
      stress represses bulk gene expression, hsp70 mRNA expression is enhanced. Post
      transcriptionally, intronless hsp70 mRNA circumvents a host of decay pathways, as
      well as heat stress-repressed pre-mRNA splicing and nuclear export. Pre
      translationally, hsp70 mRNA is excluded from stress granules and preferentially
      translated during heat stress-repressed global cap-dependent translation. Post
      translationally, nascent Hsp70 protein is thermodynamically stable at elevated
      temperatures, allowing for the commencement of chaperoning activity early after
      synthesis to attenuate the heat shock response and protect against subsequent
      injury. This review demonstrates that hsp70 mRNA expression is closely coupled
      with functional protein translation.

PMID- 21874536
TI  - Fast and fine-tuned corrections when the target of a hand movement is displaced.
AB  - To study the strategy in responding to target displacements during fast goal
      directed arm movements, we examined how quickly corrections are initiated and how
      vigorously they are executed. We perturbed the target position at various moments
      before and after movement initiation. Corrections to perturbations before the
      movement started were initiated with the same latency as corrections to
      perturbations during the movement. Subjects also responded as quickly to a second
      perturbation during the same reach, even if the perturbations were only separated
      by 60 ms. The magnitude of the correction was minimized with respect to the time
      remaining until the end of the movement. We conclude that despite being executed
      after a fixed latency, these fast corrections are not stereotyped responses but
      are suited to the circumstances.

PMID- 21874537
TI  - Long-term efficacy of pitavastatin versus simvastatin.
AB  - INTRODUCTION: Pitavastatin is a novel, potent, 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitor. This study compared the long-term efficacy of
      pitavastatin and simvastatin in dyslipidemic patients at high risk of coronary
      heart disease. METHODS: A 44-week blinded extension study was conducted at 24
      centers in five European countries for patients who had previously completed a 12
      week randomized, double-blind core study in which they received pitavastatin 4 mg
      or simvastatin 40 mg once daily. Patients originally randomized to pitavastatin 4
      mg continued at the same dose throughout the extension study (n = 121). In
      simvastatin-treated patients (n = 57), the dose was increased to 80 mg in five
      patients who had not attained the National Cholesterol Education Program (NCEP)
      target for low-density lipoprotein cholesterol (LDL-C) during the core study.
      Primary endpoints were the proportion of patients attaining the NCEP and European
      Atherosclerosis Society (EAS) LDL-C targets, and the NCEP target for non-high
      density lipoprotein cholesterol (non-HDL-C) at weeks 16 and 44. RESULTS: Of the
      178 patients who entered the extension study, 156 patients (109 in the
      pitavastatin group, 47 in the simvastatin groups) completed the 44-week treatment
      period. At week 44, NCEP and EAS targets were attained by 81.7% and 84.2%,
      respectively, of pitavastatin-treated patients, and 75.4% and 73.7%,
      respectively, of simvastatin-treated patients. NCEP targets for non-HDL-C were
      achieved by 79.2% of pitavastatin-treated patients and 70.2% of simvastatin
      treated patients. Both treatments were generally well tolerated, but pitavastatin
      4 mg was associated with a numerically lower incidence of discontinuations due to
      treatment-emergent adverse events (5.8% vs. 10.5% of patients) and a lower rate
      of myalgia (4.1% vs. 12.3%) compared with simvastatin 40-80 mg. CONCLUSION:
      Pitavastatin 4 mg provides long-term efficacy similar to that of simvastatin 40
      80 mg. Further studies should ascertain whether trends suggesting that
      pitavastatin may exhibit a more favorable long-term tolerability profile are
      statistically significant.

PMID- 21874538
TI  - Comparative efficacy of pitavastatin and simvastatin in high-risk patients: a
      randomized controlled trial.
AB  - INTRODUCTION: Despite the proven efficacy of 3-hydroxy-3-methylglutaryl coenzyme
      A reductase inhibitors (statins) in lowering total and low-density lipoprotein
      cholesterol (LDL-C), many patients do not reach recommended lipid targets. This
      study compared pitavastatin, a new and highly effective statin, and simvastatin
      in patients at high risk of coronary heart disease (CHD). The primary objective
      was to demonstrate noninferiority of pitavastatin to simvastatin. METHODS: The
      study was a phase 3, randomized, double-blind, double-dummy, parallel-group,
      active-controlled study conducted at 37 centers in five European countries.
      Following a dietary run-in period of 6-8 weeks, patients with primary
      hypercholesterolemia or combined dyslipidemia and at least two CHD risk factors
      were randomized 2:1 to receive pitavastatin 4 mg or simvastatin 40 mg once daily
      for 12 weeks. The primary efficacy variable was the change in LDL-C from
      baseline. RESULTS: In total, 355 patients were randomized, 236 to pitavastatin
      and 119 to simvastatin; 330 patients (223 and 107, respectively) completed the
      study. In the pitavastatin group, mean (+/- SD) reduction in LDL-C concentrations
      from baseline was -44.0 +/- 12.8% compared with -43.8 +/- 14.4% in the
      simvastatin group. The adjusted mean treatment difference (simvastatin-
      pitavastatin) was 0.31% (95% confidence interval -2.47, 3.09; P = 0.829), which
      was within the predefined noninferiority range. More than 80% of patients in each
      group reached recommended LDL-C targets. Pitavastatin provided a greater increase
      in high-density lipoprotein cholesterol (HDL-C; 6.8% vs. 4.5%; P = 0.083) and a
      significantly greater decrease in triglycerides (-19.8% vs. -14.8%; P = 0.044)
      than simvastatin. Both treatments were well tolerated. CONCLUSION: Pitavastatin 4
      mg is as effective as simvastatin 40 mg in lowering LDL-C in dyslipidemic
      patients at high risk of CHD, with additional effects on HDL-C and triglycerides.
      Therefore, pitavastatin may be appropriate for the management of dyslipidemic
      patients at high cardiovascular risk.

PMID- 21874539
TI  - Purification and characterization of a cytosolic Ca(2+)-independent phospholipase
      A(2) from bovine brain.
AB  - The Ca(2+)-independent phospholipase A(2) (iPLA(2)) subfamily of enzymes is
      associated with arachidonic acid (AA) release and the subsequent increase in
      fatty acid turnover. This phenomenon occurs not only during apoptosis but also
      during inflammation and lymphocyte proliferation. In this study, we purified and
      characterized a novel type of iPLA(2) from bovine brain. iPLA(2) was purified
      4,174-fold from the bovine brain by a sequential process involving DEAE-cellulose
      anion exchange, phenyl-5PW hydrophobic interaction, heparin-Sepharose affinity,
      Sephacryl S-300 gel filtration, Mono S cation exchange, Mono Q anion exchange,
      and Superose 12 gel filtration. A single peak of iPLA(2) activity was eluted at
      an apparent molecular mass of 155 kDa during the final Superose 12 gel-filtration
      step. The purified enzyme had an isoelectric point of 5.3 on two-dimensional gel
      electrophoresis (2-DE) and was inhibited by arachidonyl trifluoromethyl ketone
      (AACOCF(3)), Triton X-100, iron, and Ca(2+). However, it was not inhibited by
      bromoenol lactone (BEL), an inhibitor of iPLA(2), and adenosine triphosphate
      (ATP). The spot with the iPLA(2) activity did not match with any known protein
      sequence, as determined by matrix-assisted laser desorption/ionization time-of
      flight (MALDI-TOF) analysis. Altogether, these data suggest that the purified
      enzyme is a novel form of cytosolic iPLA(2).

PMID- 21874540
TI  - C(6)-ceramide enhances phagocytic activity of Kupffer cells through the
      production of endogenous ceramides.
AB  - Ceramide has been suggested to be not only a tumor-suppressive lipid but also a
      regulator of phagocytosis. We examined whether exogenous cell-permeable C(6)
      ceramide enhances the phagocytic activity of Kupffer cells (KCs) and affects the
      level of cellular ceramides. Rat KCs were isolated by collagenase digestion and
      differential centrifugation, using Percoll system. Phagocytic activity was
      measured by FACS analysis after incubating KCs with fluorescence-conjugated latex
      beads, and the level of cellular ceramide was analyzed by liquid chromatography
      tandem-mass spectrometry (LC-MS/MS). In this study we found that permeable C(6)
      ceramide increases the cellular levels of endogenous ceramides via a sphingosine
      recycling pathway leading to enhanced phagocytosis by KCs.

PMID- 21874541
TI  - The determinants of the willingness-to-pay for community-based prepayment scheme
      in rural Cameroon.
AB  - In rural Cameroon, many people have no access to quality healthcare services.
      This is largely attributed to lack of private out-of-pocket payment to finance
      healthcare services. A community-based prepayment health insurance scheme may be
      implemented to improve healthcare access in rural areas. This study examines the
      determinants of willingness-to-pay for a community-based prepayment healthcare
      system using a contingent valuation method conducted in rural Cameroon. To
      mitigate potential hypothetical bias, a consequential script is introduced in the
      questionnaire. The results indicate age, religion, profession, knowledge of
      community-based health insurance, awareness of usual practice in rural areas,
      involvement in association and disposable income are the key determinants of
      willingness to pay for a prepayment health scheme. On average, willingness to pay
      for the scheme by rural households is 1011 CFA francs/person/month (2.15 US
      dollars). The results underlie two important implications: first, there is
      substantial demand for a community healthcare prepayment scheme by rural poor
      households in Cameroon; second, rural households are averse to health shocks and
      hence they are willing to sacrifice monthly premium payments to protect
      themselves (and their households) from unforeseen health-related risks. If
      government could engage in social marketing strategies such as mass media
      campaigns and awareness, this could prove vital for encouraging participation by
      the rural poor in healthcare prepayment scheme in Cameroon.

PMID- 21874542
TI  - Lysosomal membrane permeabilization is involved in curcumin-induced apoptosis of
      A549 lung carcinoma cells.
AB  - We previously reported that curcumin inhibited lung cancer A549 cells growth and
      promoted cell apoptosis in vitro. In this study, we further examined the
      apoptosis-related parameters, including lysosomal damage and cathepsin
      activation, in A549 cells exposed to curcumin. We found that curcumin caused
      lysosomal membrane permeabilization (LMP) and cytosolic relocation of cathepsin B
      (cath B) and cathepsin D (cath D). However, only Z-FA-fmk (a cath B inhibitor)
      but not pepstatin A (a cath D inhibitor) inhibited curcumin-induced cell
      apoptosis, mitochondrial membrane potential loss, and cytochrome c release. The
      antioxidant N-acetylcysteine and glutathione attenuated LMP, suggesting that
      lysosomal destabilization was dependent on the elevation of reactive oxygen
      species and which precedes mitochondrial dysfunction. These findings indicated a
      novel pathway for curcumin regulation of ROS-lysosomal-mitochondrial pathway and
      provided the key mechanism of regulation of LMP in cell apoptosis, which may be
      exploited for cancer treatment.

PMID- 21874544
TI  - The combination of structural parameters and areal bone mineral density improves
      relation to proximal femur strength: an in vitro study with high-resolution
      peripheral quantitative computed tomography.
AB  - The aim of this study was to assess structural indices from high-resolution
      peripheral quantitative computed tomography (HR-pQCT) images of the human
      proximal femur along with areal bone mineral density (aBMD) and compare the
      relationship of these parameters to bone strength in vitro. Thirty-one human
      proximal femur specimens (8 men and 23 women, median age 74 years, range 50-89)
      were examined with HR-pQCT at four regions of interest (femoral head, neck, major
      and minor trochanter) with 82 MUm and in a subgroup (n = 17) with 41 MUm
      resolution. Separate analyses of cortical and trabecular geometry, volumetric BMD
      (vBMD), and microarchitectural parameters were obtained. In addition, aBMD by
      dual-energy X-ray absorptiometry (DXA) was performed at conventional hip regions
      and maximal compressive strength (MCS) was determined in a side-impact
      biomechanical test. Twelve cervical and 19 trochanteric fractures were confirmed.
      Geometry, vBMD, microarchitecture, and aBMD correlated significantly with MCS,
      with Spearman's correlation coefficients up to 0.77, 0.89, 0.90, and 0.85 (P <
      0.001), respectively. No differences in these correlations were found using 41
      MUm compared to 82 MUm resolution. In multiple regression analysis of MCS, a
      combined model (age- and sex-adjusted) with aBMD and structural parameters
      significantly increased R (2) values (up to 0.90) compared to a model holding
      aBMD alone (R (2) up to 0.78) (P < 0.05). Structural parameters and aBMD are
      equally related to MCS, and both cortical and trabecular structural parameters
      obtained from HR-pQCT images hold information on bone strength complementary to
      that of aBMD.

PMID- 21874543
TI  - Therapeutic inhibition of fatty acid oxidation in right ventricular hypertrophy:
      exploiting Randle's cycle.
AB  - Right ventricular hypertrophy (RVH) and RV failure are major determinants of
      prognosis in pulmonary hypertension and congenital heart disease. In RVH, there
      is a metabolic shift from glucose oxidation (GO) to glycolysis. Directly
      increasing GO improves RV function, demonstrating the susceptibility of RVH to
      metabolic intervention. However, the effects of RVH on fatty acid oxidation
      (FAO), the main energy source in adult myocardium, are unknown. We hypothesized
      that partial inhibitors of FAO (pFOXi) would indirectly increase GO and improve
      RV function by exploiting the reciprocal relationship between FAO and GO
      (Randle's cycle). RVH was induced in adult Sprague-Dawley rats by pulmonary
      artery banding (PAB). pFOXi were administered orally to prevent (trimetazidine,
      0.7 g/L for 8 weeks) or regress (ranolazine 20 mg/day or trimetazidine for 1
      week, beginning 3 weeks post-PAB) RVH. Metabolic, hemodynamic, molecular,
      electrophysiologic, and functional comparisons with sham rats were performed 4 or
      8 weeks post-PAB. Metabolism was quantified in RV working hearts, using a dual
      isotope technique, and in isolated RV myocytes, using a Seahorse Analyzer. PAB
      induced RVH did not cause death but reduced cardiac output and treadmill walking
      distance and elevated plasma epinephrine levels. Increased RV FAO in PAB was
      accompanied by increased carnitine palmitoyltransferase expression; conversely,
      GO and pyruvate dehydrogenase (PDH) activity were decreased. pFOXi decreased FAO
      and restored PDH activity and GO in PAB, thereby increasing ATP levels. pFOXi
      reduced the elevated RV glycogen levels in RVH. Trimetazidine and ranolazine
      increased cardiac output and exercise capacity and attenuated exertional lactic
      acidemia in PAB. RV monophasic action potential duration and QTc interval
      prolongation in RVH normalized with trimetazidine. pFOXi also decreased the mild
      RV fibrosis seen in PAB. Maladaptive increases in FAO reduce RV function in PAB
      induced RVH. pFOXi inhibit FAO, which increases GO and enhances RV function.
      Trimetazidine and ranolazine have therapeutic potential in RVH.

PMID- 21874545
TI  - Osteocyte deficiency in hip fractures.
AB  - Osteocytes play a central role in the regulation of bone remodeling. The aim of
      this study was to explore osteocyte function, and particularly the expression of
      SOST, a Wnt inhibitor, in patients with hip fractures. Serum sclerostin levels
      were measured by ELISA. The expression of several osteocytic genes was studied by
      quantitative PCR in trabecular samples of the femoral head of patients with hip
      fractures, hip osteoarthritis and control subjects. The presence of sclerostin
      protein and activated caspase 3 was revealed by immunostaining. There were no
      significant differences in serum sclerostin between the three groups. Patients
      with fractures have fewer lacunae occupied by osteocytes (60 +/- 5% vs. 64 +/- 6%
      in control subjects, P = 0.014) and higher numbers of osteocytes expressing
      activated caspase 3, a marker of apoptosis. The proportion of sclerostin-positive
      lacunae was lower in patients with fractures than in control subjects (34 +/- 11%
      vs. 69 +/- 10%, P = 2 * 10(-8)). The proportion of sclerostin-positive osteocytes
      was also lower in patients. RNA transcripts of SOST, FGF23 and PHEX were also
      less abundant in fractures than in control bones (P = 0.002, 5 * 10(-6), and
      0.04, respectively). On the contrary, in patients with osteoarthritis, there was
      a decreased expression of SOST and FGF23, without differences in PHEX transcripts
      or osteocyte numbers. Osteocyte activity is altered in patients with hip
      fractures, with increased osteocyte apoptosis and reduced osteocyte numbers, as
      well as decreased transcription of osteocytic genes. Therefore, these results
      suggest that an osteocyte deficiency may play a role in the propensity to hip
      fractures.

PMID- 21874546
TI  - Behavioural responses of the supralittoral amphipod Talitrus saltator (Montagu)
      to trace metals contamination.
AB  - We investigated behavioural responses (locomotor activity and substrate
      selection) of the amphipod Talitrus saltator after laboratory exposure to
      different concentrations of Hg, Cu and Cd. Locomotor activity, measured with a
      microwave radar device, was assessed in animals exposed to contaminated sand and
      in sandhoppers previously kept for 48 h in contaminated seawater and tested in
      clean sand. The contents of Hg, Cu and Cd in T. saltator tissues were measured at
      the end of pre-exposure to contaminated seawater and after 7 days of exposure to
      contaminated sand. Substrate selection tests were carried out in a binary choice
      arena. Tests in contaminated sand showed that sandhopper locomotor activity
      varied in a dose-dependent manner in the presence of Cu and Hg (at lower Hg
      concentration they were more active during daytime) but did not show significant
      changes in Cd-exposed animals except for disappearance of the typical circadian
      activity pattern. Pre-exposure to trace metals in seawater induced a significant
      decrease of movements for all metals, although the effects varied according to
      the toxicity of the metal. Trace metals analyses showed that tissue
      concentrations of Hg, Cu and Cd were related to their concentrations in the test
      medium. Substrate selection tests showed avoidance of contaminated sand only when
      sandhoppers were tested in the presence of both concentrations of Hg and at the
      higher concentration of Cu. In conclusion, locomotor activity and avoidance
      behaviour of T. saltator could be used as behavioural biomarkers of trace metals
      exposure.

PMID- 21874547
TI  - Mercury and other heavy metals in free-ranging mink of the lower Great Lakes
      basin, Canada, 1998-2006.
AB  - Mercury concentrations were examined in livers of free-ranging mink (Neovison
      vison) trapped in the lower Great Lakes basin from 1998 to 2006. Significant
      geographic variation in total mercury levels was found in mink from 13 Great
      Lakes locations, many of which are within Great Lakes Areas of Concern (AOCs).
      Total mercury levels in mink from these locations were generally low to moderate,
      with means (+/-SE) ranging from 0.99 (+/-0.36) MUg/g dry weight in mink from
      inland Lake Erie to 7.31 (+/-1.52) MUg/g in mink from Walpole Island in the St.
      Clair River AOC. Overall, mercury exposure was highest in mink trapped in
      locations associated with large riverine wetlands. Total mercury concentrations
      were negatively related to the percentage of mercury present as methylmercury and
      positively related to selenium concentrations, consistent with increasing
      demethylation of methylmercury with increasing total mercury concentrations. One
      year old mink had significantly higher levels of mercury and selenium than mink
      under 1 year but similar to mink 2 years of age and older. Mercury levels were
      below those associated with mercury toxicity. Concentrations of cadmium, lead and
      arsenic were low and largely associated with environmental background levels.
      Significant age and sex effects were found for cadmium. Lead levels were
      significantly lower in mink infected by the lung nematode parasite compared to
      uninfected animals. Further studies of biomagnification of methylmercury in
      wetland environments, where top predators such as mink may be an increased risk
      of exposure, are warranted.

PMID- 21874548
TI  - Investigating the modality specificity of response selection using a temporal
      flanker task.
AB  - The neurocognitive architecture for response selection is uncertain. Some
      theorists suggest that it is mediated by an amodal central mechanism, whereas
      others propose a set of independent control mechanisms. In a functional
      neuroimaging experiment, we investigated the nature of response selection by
      examining how its underlying brain mechanisms are affected by stimulus modality.
      To do this, we used a modified flanker task, in which the target and flanker
      (distractor) stimuli differed in time rather than space, making it accessible for
      both visual and auditory stimuli. As in the traditional flanker task, larger
      reaction times were observed for incongruent than congruent trials (i.e., a
      congruency effect) for both modalities. Congruency affected brain activation for
      both modalities in prefrontal cortex, parietal cortex, and the putamen. Modality
      dependent activation was found in additional prefrontal and parietal regions for
      the visual modality and in left inferior prefrontal cortex for the auditory
      modality. Modality-dependent activity specifically related to response congruency
      was also found in sensory cortical regions. These data suggest that modality
      affects the brain regions throughout the cortex mediating response selection even
      for conceptually identical stimuli and tasks. They are consistent with the
      hypothesis that (at least partially) independent brain networks mediate response
      selection and that input modality may be a powerful factor for organizing neural
      activity to support task performance.

PMID- 21874549
TI  - Spontaneous spinal epidural haematoma during Factor Xa inhibitor treatment
      (Rivaroxaban).
AB  - We report on a 61-year-old female patient who developed a spontaneous spinal
      epidural haematoma (SSEH) after being treated by rivaroxaban, a new agent for the
      prevention of venous thromboembolic events in orthopaedic surgery. Although the
      pathogenesis of SSEH is unclear, anticoagulant therapy is a known risk factor.
      The patient sustained a sudden onset of severe back pain in the thoracic spine,
      followed by paraplegia below T8, 2 days after proximal tibial osteotomy and
      rivaroxaban therapy. Magnetic resonance imaging (MRI) of the whole spine
      demonstrated a ventral SSEH from C2 to T8. Whilst preparing for the emergency
      evacuation of the SSEH, the neurological symptoms recovered spontaneously 4 h
      after onset without surgery. After monitored bed rest for 48 h the MRI was
      repeated and the SSEH was no longer present. This rare condition of spinal cord
      compression and unusually rapid spontaneous recovery has not previously been
      reported following rivaroxaban therapy.

PMID- 21874550
TI  - Balance control in very old adults with and without visual impairment.
AB  - Good balance, an important ability in controlling body movement, declines with
      age. Also, balance appears to decrease when visual input is restricted, while
      this has been poorly investigated among visually impaired very old adults. The
      objective of this study is thus to explore whether the balance control of the
      very old differs with varying degrees of visual impairment. This cross-sectional
      study was conducted in community centers and residential care homes. Thirty-three
      visually impaired (17 = low vision; 16 = blind) and 15 sighted elderly aged >= 70
      years participated in the study. All participants were assessed: (1) concentric
      isokinetic strength of the knee extensors and flexors; (2) a sensory organization
      test to measure their ability to use somatosensory, visual, and vestibular
      information to control standing balance; (3) a perturbed double-leg stance test
      to assess the ability of the automatic motor system to quickly recover following
      an unexpected external disturbance; (4) the five times sit-to-stand test.
      Compared with low-vision subjects, the sighted elderly achieved higher peak
      torque-to-body weight ratios in concentric knee extension. The sighted elderly
      showed less body sway than the low vision and blind subjects in sensory
      conditions where they benefited from visual inputs to help them maintain standing
      balance. The sighted and low-vision subjects achieved smaller average body sway
      angles during forward and backward platform translations compared to the blind
      subjects. Low vision and blindness decrease balance control in elderly.

PMID- 21874551
TI  - Detrimental effects of west to east transmeridian flight on jump performance.
AB  - It is perceived that long haul travel, comprising of rapid movement across
      several time zones is detrimental to performance in elite athletes. However,
      available data is equivocal on the impact of long haul travel on maximal
      explosive movements. The aim of this study was to quantify the impact of long
      haul travel on lower body muscle performance. Five elite Australian skeleton
      athletes (1 M, 4 F) undertook long haul flight from Australia to Canada
      (LH(travel)), while seven national team Canadian skeleton athletes (1 M, 6 F)
      acted as controls (NO(travel)). Lower body power assessments were performed once
      per day between 09:30 and 11:00 h local time for 11 days. Lower body power tests
      comprised of box drop jumps, squat jump (SJ) and countermovement jumps (CMJ). The
      LH(travel) significantly decreased peak and mean SJ velocity but not CMJ velocity
      in the days following long haul flight. CMJ height but not SJ height decreased
      significantly in the LH(travel) group. The peak velocity, mean velocity and jump
      power eccentric utilisation ratio for the LH(travel) group all significantly
      increased 48 h after long haul flight. Anecdotally athletes perceived themselves
      as 'jet-lagged' and this corresponded with disturbances observed in 'one-off'
      daily jumping ability between 09:30 and 11:00 h after eastward long haul travel
      from Australia to North America when compared to non-travel and baseline
      controls.

PMID- 21874552
TI  - Variability in physical activity patterns as measured by the SenseWear Armband:
      how many days are needed?
AB  - To examine sources of variance in objectively measured physical activity and to
      determine the number of monitoring days needed to quantify physical activity
      patterns reliably, 394 Flemish adults (41.1 +/- 9.9 years) were monitored during
      7 days, using the SenseWear Armband. Differences between weekdays, Saturday and
      Sunday were examined with repeated measures ANOVA's. Variance components were
      estimated for subject, weekday and residual error using data from Mondays through
      Fridays and used to calculate the reliability of 1-5 monitoring weekdays.
      Saturday was more and Sunday less active than an average weekday. Inter
      individual variability was the largest source of variance (54.4-67.9%) for
      physical activity level (PAL), energy expenditure, inactivity, light, moderate
      and total physical activity. Intra-individual variability accounted for 31.8
      44.8% and weekday for 0.1-1.1% of total variance. Intra-individual variability
      was the largest source of variance for vigorous activity in both sexes and steps
      in women. At least, 3 monitoring weekdays were required to achieve a reliability
      of 0.80 for PAL, energy expenditure, inactivity, light, moderate and total
      physical activity. All 5 weekdays should be monitored to reach acceptable
      reliability for steps. Five weekdays resulted in a reliability of 0.58-0.60 for
      vigorous activity. Both Saturday and Sunday and at least 3 weekdays need to be
      monitored to obtain reliable measures of habitual physical activity.

PMID- 21874553
TI  - Similarity in physiological and perceived exertion responses to exercise at
      continuous and intermittent critical power.
AB  - The purpose of this study was to compare the physiological responses [oxygen
      uptake (VO(2)), heart rate (HR) and blood lactate concentrations ([BLa])] and the
      rating of perceived exertion (RPE) response until exhaustion (TTE) at the
      continuous (CP(c)) and intermittent (CP(i)) critical power workloads. Ten
      moderately active men (25.5 +/- 4.2 years, 74.1 +/- 8.0 kg, 177.6 +/- 4.9 cm)
      participated in this study. The incremental test was applied to determine the
      highest values of oxygen uptake (VO(2max)), heart rate (HR(max)), blood lactate
      concentrations ([BLa(max)]), and maximal aerobic power (MAP). Continuous and
      intermittent exhaustive predictive trials were performed randomly. The hyperbolic
      relation between power and time was used to estimate CP(c) and CP(i). CP(i) was
      derived from predictive trial results at an effort and recovery ratio of 30:30 s.
      Exercise at CP(c) and CP(i) as well as the physiological and RPE responses were
      measured until exhaustion. The values of physiological variables during CP(c) and
      CP(i) did not differ in either TTE test and were lower than the VO(2max), HR(max)
      and [BLa(max)] values. RPE was maximal at the end of exercise at CP(c) and CP(i).
      There was a high correlation between VO(2max) (L min(-1)) and CP(c) and CP(i)
      intensities (r >= 0.90) and between MAP, CP(c) and CP(i) (r >= 0.95). Similar
      physiological and RPE responses were found at CP(c) and CP(i) for the times
      analyzed.

PMID- 21874554
TI  - Effect of short-term cryostimulation on antioxidative status and its clinical
      applications in humans.
AB  - Whole body cryostimulation (WBCT) is becoming popular in medicine and sport as an
      adjuvant form of treatment since late 1970s. Only a few works concerning
      antioxidant protection after WBCT have been published. The aim of this study was
      to determine the effect of a ten 3-min-long exposures (one exposure per day) to
      cryogenic temperature (-130  degrees C) on the level of total antioxidant status
      (TAS), activity of selected antioxidant enzyme superoxide dismutase (SOD) and
      main non-enzymatic antioxidant-uric acid (UA) in WBCT study group (man n = 24;
      female n = 22) and non-WBCT control subjects (man n = 22; female n = 26).
      Moreover, we evaluated the lipid peroxidation measured as thiobarbituric acid
      reactive substances products. Their blood samples were collected twice at an
      interval of 10 days in both study group and control subjects. The activity of
      antioxidant enzyme and lipid peroxidation was assayed in erythrocytes, while the
      concentration of uric acid was measured in plasma. After completing a total of
      ten WBCT sessions a significant increase (p < 0.001) of TAS and UA levels in
      plasma (p < 0.001) in comparison to non-WBCT was observed. Our data showed that
      there was statistically significant increase of the activities of SOD in
      erythrocytes obtained from WBCT study group compared to non-WBCT controls after
      10 days of treatment (p < 0.001). It was concluded that expositions to extremely
      low temperatures use in cryostimulation improve the antioxidant capacity of
      organism.

PMID- 21874556
TI  - Determination of the myocardial area at risk with pre- versus post-reperfusion
      imaging techniques in the pig model.
AB  - The purpose of this study was to compare the accuracy of post-reperfusion cardiac
      magnetic resonance (CMR) and pre-reperfusion multidetector computed tomography
      (MDCT) imaging to measure the size of the area at risk (AAR), using pathology as
      a reference technique in a porcine acute myocardial infarction model. Fifteen
      pigs underwent balloon-induced coronary artery occlusion for 40 min followed by
      reperfusion. The AAR was assessed with arterial enhanced MDCT performed during
      occlusion, while two different T2 weighted (T2W) CMR imaging sequences and the
      contrast-enhanced (ce-) CMR endocardial surface length (ESL) were performed after
      90 min of reperfusion. Animals were euthanized and the AAR was assessed by
      pathology. Additional measurements of the myocardial water content in the AAR,
      remote and the AAR border zones were performed. AAR by pathology best correlated
      with measurements made by MDCT (R(2) = 0.88; p < 0.001) with little bias on Bland
      Altman plots (bias 2.5%, SD 6.1% LV area). AAR measurements obtained by T2W STIR,
      T2W ACUTE sequences or the ESL on ce-CMR showed a fair correlation with pathology
      (R(2) = 0.72, R(2) = 0.65 and R(2) = 0.69, respectively; all p <= 0.001), but
      significantly overestimated the size of the AAR with important bias (17.4 +/-
      10.8% LV area; 11.7 +/- 11.0% LV area; 13.0 +/- 10.3% LV area, respectively). The
      myocardial water content in the AAR border zones was significantly higher than
      the remote (82.8 vs. 78.8%; p < 0.001). Our data suggest that post-reperfusion
      imaging methods overestimated the AAR likely due to the presence of edema outside
      of the boundaries of the AAR. Pre-reperfusion arterial enhanced MDCT showed the
      greatest accuracy for the assessment of the AAR.

PMID- 21874555
TI  - Colocalization in vivo and association in vitro of perlecan and elastin.
AB  - We have colocalized elastin and fibrillin-1 with perlecan in extracellular matrix
      of tensional and weight-bearing connective tissues. Elastin and fibrillin-1 were
      identified as prominent components of paraspinal blood vessels, and posterior
      longitudinal ligament in the human fetal spine and outer annulus fibrosus of the
      fetal intervertebral disc. We also colocalized perlecan with a synovial elastic
      basal lamina, where the attached synovial cells were observed to produce
      perlecan. Elastin, fibrillin-1 and perlecan were co-localized in the intima and
      media of small blood vessels in the synovium and in human fetal paraspinal blood
      vessels. Elastic fibers were observed at the insertion point of the anterior
      cruciate ligament to bone in the ovine stifle joint where they colocalized with
      perlecan. Elastin has not previously been reported to be spatially associated
      with perlecan in these tissues. Interactions between the tropoelastin and
      perlecan heparan sulfate chains were demonstrated using quartz crystal
      microbalance with dissipation solid phase binding studies. Electrostatic
      interactions through the heparan sulfate chains of perlecan and core protein
      mediated the interactions with tropoelastin, and were both important in the
      coacervation of tropoelastin and deposition of elastin onto perlecan immobilized
      on the chip surface. This may help us to understand the interactions which are
      expected to occur in vivo between the tropoelastin and perlecan to facilitate the
      deposition of elastin and formation of elastic microfibrils in situ and would be
      consistent with the observed distributions of these components in a number of
      connective tissues.

PMID- 21874557
TI  - Mitochondrial biogenesis and PGC-1alpha deacetylation by chronic treadmill
      exercise: differential response in cardiac and skeletal muscle.
AB  - Posttranslational modifications of the transcriptional coactivator PGC-1alpha by
      the deacetylase SIRT1 and the kinase AMPK are involved in exercise-induced
      mitochondrial biogenesis in skeletal muscle. However, similar investigations have
      not been performed in the left ventricle (LV). Here, we tested whether treadmill
      training (12 weeks) modifies PGC-1alpha and mitochondrial biogenesis in
      gastrocnemius muscle and LV of C57BL/6 J wild-type mice and IL-6-deficient mice
      with a reported impairment in muscular AMPK activation similarly. Physical
      activity lowered the plasma insulin and glucose in both mouse strains, suggesting
      improved insulin sensitivity. The gastrocnemius muscle of IL-6-deficient mice
      showed reduced mitochondrial respiration and enzyme activity, which was partially
      normalized after training. Chronic exercise enhanced the mitochondrial biogenesis
      in gastrocnemius muscle as indicated by increased mRNA or protein expression of
      primary mitochondrial transcripts, higher mtDNA content and increased citrate
      synthase activity. Parallel to these changes, we observed AMPK activation, SIRT1
      induction and PGC-1alpha deacetylation. Chronic treadmill training resulted in a
      mild cardiac hypertrophy in both mouse strains. However, none of these changes
      observed in skeletal muscle were detected in the LV (both mouse strains) with the
      exception of AMPK activation and a mildly increased succinate-dependent
      respiration. Thus, chronic endurance training induces a sustained mitochondrial
      biogenic response in mouse gastrocnemius muscle but not in the LV. Although AMPK
      activation occurs in both muscular organs, the absence of SIRT1-dependent PGC
      1alpha deacetylation may be responsible for this significant difference. AMPK
      activation by IL-6 appears to be dispensable for the mitochondrial biogenic
      responses to chronic treadmill exercise.

PMID- 21874558
TI  - Cerebrovascular diseases in nuclear workers first employed at the Mayak PA in
      1948-1972.
AB  - Incidence and mortality from cerebrovascular diseases (CVD) (430-438 ICD-9 codes)
      have been studied in a cohort of 18,763 workers first employed at the Mayak
      Production Association (Mayak PA) in 1948-1972 and followed up to the end of
      2005. Some of the workers were exposed to external gamma-rays only while others
      were exposed to a mixture of external gamma-rays and internal alpha-particle
      radiation due to incorporated (239)Pu. After adjusting for non-radiation factors,
      there were significantly increasing trends in CVD incidence with total absorbed
      dose from external gamma-rays and total absorbed dose to liver from internal
      alpha radiation. The CVD incidence was statistically significantly higher among
      workers with total absorbed external gamma-ray doses greater than 0.20 Gy
      compared to those exposed to lower doses; the data were consistent with a linear
      trend in risk with external dose. The CVD incidence was statistically
      significantly higher among workers with total absorbed internal alpha-radiation
      doses to liver from incorporated (239)Pu greater than 0.025 Gy compared to those
      exposed to lower doses. There was no statistically significant trend in CVD
      mortality risk with either external gamma-ray dose or internal alpha-radiation
      dose to liver. The risk estimates obtained are generally compatible with those
      from other large occupational studies, although the incidence data point to
      higher risk estimates compared to those from the Japanese A-bomb survivors.
      Further studies of the unique cohort of Mayak workers chronically exposed to
      external and internal radiation will allow improving the reliability and
      validating the radiation safety standards for occupational and public exposure.

PMID- 21874559
TI  - Comparative inhibition by bilastine and cetirizine of histamine-induced wheal and
      flare responses in humans.
AB  - OBJECTIVE AND DESIGN: Comparison of bilastine and cetirizine in inhibiting skin
      wheal and flare responses over 24 h. SUBJECTS: Twenty-one healthy male volunteers
      (aged 19-44 years). TREATMENT AND METHODS: Volunteers were randomised to receive
      single oral doses of 20 or 50 mg bilastine, 10 mg cetirizine or placebo before
      provocation of wheal and flare responses to 100 mg/ml histamine by skin prick
      1.5, 4, 8, 12 and 24 h later. RESULTS: There were no significant differences
      between overall inhibitions of wheal or flare by 20 mg bilastine and 10 mg
      cetirizine. Bilastine was faster in onset than cetirizine, inhibitions of wheal
      and flare at 1.5 h being 89 +/- 3 versus 44 +/- 14% (P = 0.011) and 85 +/- 4
      versus 45 +/- 14% (P = 0.016), respectively (Student's t test). At 1.5 h, both
      wheals and flares were inhibited by >70% in 11/12 volunteers taking bilastine and
      3/11 taking cetirizine (P = 0.003, Fisher's exact test). There were no
      significant differences between the drugs at later times. Bilastine 50 mg had a
      longer duration of action than bilastine 20 mg. CONCLUSIONS: Both 20 mg bilastine
      and 10 mg cetirizine are effective and of long duration in reducing histamine
      induced wheal and flare responses, the major difference between the two drugs
      being the more rapid onset of action of bilastine.

PMID- 21874560
TI  - Adherence to a Mediterranean diet and onset of disability in older persons.
AB  - Higher adherence to a Mediterranean-type diet is linked to lower risk of
      mortality, cardiovascular disease and Alzheimer's disease while its association
      with disability has never been assessed. The aim of the study was to investigate
      the relation between adherence to a Mediterranean diet (MeDi) and disability in
      activities of daily living. The study sample consisted of 1,410 individuals from
      Bordeaux, France, included in 2001-2002 in the Three-City Study and re-examined
      at least once over 5 years. Adherence to a MeDi (scored as 0-9) was computed from
      a food frequency questionnaire and 24H recall. Disability in Basic and
      Instrumental ADL (B-IADL) was evaluated on the Lawton-Brody and Katz scales.
      Statistical analyses were stratified by gender and adjusted for potential
      confounders. No association between MeDi adherence and baseline disability in B
      IADL was highlighted in men or in women in multivariate models. Risk of onset of
      disability in B-IADL over time was not significantly associated with MeDi
      adherence in men. In women, MeDi adherence was inversely associated with the risk
      of incident disability in B-IADL (HR = 0.90, 95% Confidence Interval 0.82-0.98
      for 1 point of the score). Women with the highest MeDi adherence (score 6-8) had
      a 50% (22-68%) relative risk reduction of incident disability in B-IADL over time
      than women in the lowest MeDi category (score 0-3). In addition to its well
      documented beneficial effects on health, adherence to a Mediterranean-type diet
      could contribute to slow down the disablement process in women.

PMID- 21874561
TI  - Early postural blood pressure response and cause-specific mortality among middle
      aged adults: what is the role of diastolic blood pressure?

PMID- 21874562
TI  - Time to act on headache disorders.

PMID- 21874563
TI  - LKB1/ STK11, Peutz-Jeghers syndrome and cancer. Introduction.

PMID- 21874564
TI  - Comments on 'evaluation of a pulse oximeter sensor tester'.

PMID- 21874565
TI  - CIP2A with survivin protein expressions in human non-small-cell lung cancer
      correlates with prognosis.
AB  - Cancerous inhibitor of protein phosphatase 2A (CIP2A) and survivin are aberrantly
      expressed in a wide range of human cancers, including lung tumors. In order to
      assess the expressions of these two proteins in Chinese non-small-cell lung
      cancer (NSCLC) patients and determine their correlation with prognosis, NSCLC
      tissues and adjacent non-cancerous normal lung tissues were collected from 97
      patients undergoing surgical treatment and evaluated by immunohistochemistry
      staining. CIP2A or survivin immunoreactivity was detected in significantly more
      NSCLC tissues than in adjacent non-cancerous lung tissues (P < 0.05). Moreover,
      CIP2A expression in NSCLC correlated with TNM stage, while survivin expression
      correlated with TNM stage and lymph node metastasis. Kaplan-Meier survival
      analysis showed that the overall survival times in patients expressing either
      CIP2A or survivin protein in NSCLC were shorter. COX regression analysis
      indicated that expression of CIP2A protein was an independent prognostic factor
      for NSCLC patients (HR = 3.631, P = 0.015). Therefore, CIP2A expression in
      Chinese NSCLC patients may be a useful biomarker of biological malignancy.

PMID- 21874566
TI  - Letter to the editor regarding the article by Uzunoglu et al.

PMID- 21874567
TI  - Angiotensin-converting enzyme insertion/deletion polymorphism and the risk of
      prostate cancer in the Han population of China.
AB  - As a main effector in the renin-angiotensin system, the angiotensin II plays a
      critical role in cell proliferation and angiogenesis. The change between
      angiotensin II and its precursor is conducted by the angiotensin-converting
      enzyme. The association between angiotensin-converting enzyme insertion/deletion
      polymorphism and the activity of angiotensin-converting enzyme was testified.
      Furthermore, previous researches proved the association between angiotensin
      converting enzyme activity and the risk of prostate cancer. Therefore, we
      conducted a case-control study in the Han population of China to elaborate the
      relation between the angiotensin-converting enzyme insertion/deletion
      polymorphism and prostate cancer. DNA was extracted from blood samples collected
      from 189 pathologically diagnosed prostate cancer patients and 290 cancer-free
      subjects. The angiotensin-converting enzyme insertion/deletion genotype was
      determined by polymerase chain reaction analysis. Stratified analyses on age (<71
      or >= 71), cancer stage (localized or advanced), Gleason score (<7 or >= 7) and
      PSA level (<20 ng/ml or >= 20 ng/ml) were performed. We found the II genotype (OR
      = 0.304 95%CI (0.180,0.515), P < 0.001) and I allele (OR = 0.547
      95%CI(0.421,0.711), P < 0.001) were associated with a decreased risk of prostate
      cancer compared with the DD genotype and D allele. The DD genotype was related to
      patients with aggressive stage of prostate cancer (OR = 2.214 95%CI(1.169,
      4.194), P = 0.014) and patients diagnosed of prostate cancer at a relatively
      early age (OR = 0.513 95%CI(0.272, 0.965), P = 0.037). The results of our
      experiment supported the hypothesis that the angiotensin-converting enzyme
      insertion/deletion polymorphism, a potential risk factor in carcinogenesis,
      played an important role in the Han population of China.

PMID- 21874568
TI  - Acute testicular ischemia caused by incarcerated inguinal hernia.
AB  - BACKGROUND: Acute testicular ischemia caused by an incarcerated inguinal hernia
      usually affects infants. There are few reports of diagnosis using US, and the
      effect of long-standing reducible hernias on testicular growth in infants and
      children is unknown. OBJECTIVE: The objectives of this study were to determine
      the incidence of testicular ischemia secondary to an incarcerated inguinal hernia
      at scrotal sonography and to determine the effect on testicular size at
      diagnosis. MATERIALS AND METHODS: A hospital database was used to locate scrotal
      sonography examinations documenting an inguinal hernia, and images were reviewed
      for signs of testicular ischemia. Testicular volumes were compared using the
      Wilcoxon signed rank test. RESULTS: A total of 147 patients were identified with
      an inguinal hernia (age 1 day to 23 years, average 6 years). Ten patients (6.8%)
      had associated testicular ischemia (age 3 weeks to 6 months, average 9 weeks) and
      showed a statistically significant increase in ipsilateral testicular size
      compared to the contralateral testicle (P = 0.012). Patients without testicular
      ischemia did not show a significant difference in testicular size, regardless of
      patient age. CONCLUSION: An incarcerated inguinal hernia should be considered as
      a cause of acute testicular ischemia in infants younger than 6 months of age.

PMID- 21874569
TI  - Comparison of image quality and radiation dose of different pulmonary CTA
      protocols on a 128-slice CT: high-pitch dual source CT, dual energy CT and
      conventional spiral CT.
AB  - OBJECTIVES: To compare image quality and radiation dose of high-pitch dual-source
      computed tomography (DSCT), dual energy CT (DECT) and conventional single-source
      spiral CT (SCT) for pulmonary CT angiography (CTA) on a 128-slice CT system.
      METHODS: Pulmonary CTA was performed with five protocols: high-pitch DSCT (100
      kV), high-pitch DSCT (120 kV), DECT (100/140 kV), SCT (100 kV), and SCT (120 kV).
      For each protocol, 30 sex, age, and body-mass-index (mean 25.3 kg/m(2)) matched
      patients were identified. Retrospectively, two observers subjectively assessed
      image quality, measured CT attenuation (HU+/-SD) at seven central and peripheral
      levels, and calculated signal-to-noise-ratio (SNR) and contrast-to-noise-ratio
      (CNR). Radiation exposure parameters (CTDIvol and DLP) were compared. RESULTS:
      Subjective image quality was rated good to excellent in >92% (>138/150) with an
      interobserver agreement of 91.4%. The five protocols did not significantly differ
      in image quality, neither by subjective, nor by objective measures (SNR, CNR). By
      contrast, radiation exposure differed between protocols: significant lower
      radiation was achieved by using high-pitch DSCT at 100 kV (p < 0.01 in all).
      Radiation exposure of DECT was in between SCT at 100 kV and 120 kV. CONCLUSIONS:
      SCT, high-pitch DSCT, and DECT protocols techniques result in similar subjective
      and objective image quality, but radiation exposure was significantly lower with
      high-pitch DSCT at 100 kV. KEY POINTS: New CT protocols show promising results in
      pulmonary embolism assessment. High-pitch dual-source CT (DSCT) at 100 kV
      provides radiation dose savings for pulmonary CTA. High-pitch DSCT at 100 kV
      maintains diagnostic image quality for pulmonary CTA. Dual energy CT uses more
      radiation but also provides lung perfusion evaluation. Whether the additional
      perfusion data is worth the extra radiation remains undetermined.

PMID- 21874570
TI  - Effectiveness of a three-dimensional dual gradient echo two-point Dixon technique
      for the characterization of adrenal lesions at 3 Tesla.
AB  - OBJECTIVE: To compare the sensitivity, specificity, and diagnostic accuracy of
      fat-only datasets reconstructed using a two-point Dixon technique, with
      corresponding opposed-phase (OP) and in-phase (IP) datasets for characterization
      of adrenal lesions at 3 Tesla (T). METHODS: Fifty-nine patients (21 male, 38
      female) with 66 adrenal lesions (49 adenomas, 17 nonadenomas) underwent 3D dual
      gradient-echo 3-T adrenal MR imaging with reconstruction of OP/IP and fat/water
      datasets. Sensitivity, specificity, and diagnostic accuracy were compared between
      OP/IP datasets, using the signal intensity index (SII), and fat/water datasets,
      using the fat fraction and fat ratio. Four radiologists qualitatively assessed
      OP/IP and fat-only datasets for reader confidence in lesion characterization and
      image quality. RESULTS: There were significant differences between adenomas and
      nonadenomas with regard to mean SII, fat fraction, and fat ratio (P < 0.001).
      There was no significant difference in mean diagnostic accuracy among different
      evaluation methods using OP/IP and fat/water datasets. Mean readers' scores for
      lesion characterization were significantly higher for adenomas than for
      nonadenomas using OP/IP and fat-only datasets. There was no significant
      difference between the two datasets regarding mean readers' scores for image
      quality. CONCLUSION: Fat-only images can readily differentiate adrenal adenomas
      from nonadenomas, with diagnostic accuracy comparable to OP/IP images.

PMID- 21874571
TI  - Head-to-head comparison of contrast-enhanced cardiovascular magnetic resonance
      and 201Thallium single photon emission computed tomography for prediction of
      reversible left ventricular dysfunction in chronic ischaemic heart disease.
AB  - Delayed contrast-enhanced cardiovascular magnetic resonance (DE-CMR) allows
      assessment of reversibility of myocardial dysfunction. Comparative data to other
      modalities is scarce. Purpose of this study was to compare DE-CMR and
      (201)Thallium single photon emission computed tomography (SPECT) for prediction
      of reversible left ventricular (LV) dysfunction in patients with chronic
      ischaemic heart disease. Fifty-four patients with LV dysfunction (mean ejection
      fraction (EF) 35 +/- 8%) scheduled to undergo myocardial revascularization
      underwent DE-CMR and SPECT. Cine CMR was performed at baseline and at 8 months
      follow-up for assessment of regional and global myocardial function. Myocardial
      viability was determined by the segmental extent of delayed enhancement for DE
      CMR, and by quantitative analysis of tracer uptake for SPECT, and was correlated
      to functional recovery after revascularization. After revascularization, 172
      (49%) of 350 dysfunctional segments improved at follow-up cine CMR. Sensitivity
      and specificity for the prediction of functional recovery was 92 and 88%,
      respectively, for DE-CMR as compared to 86% (P = 0.4) and 56% (P = 0.001) for
      SPECT. Global LV function showed an increase of EF > 5% in 22 (41%) patients. The
      DE-CMR derived viability ratio (dysfunctional but viable myocardium) of 0.46
      (sensitivity 91%, specificity 91%) was identified as predictor of increase in EF
      > 5% (P = 0.02), whereas the corresponding SPECT parameters were not predictive.
      DE-CMR compares favorably to SPECT for the prediction of regional and global
      improvement in LV function in the setting of chronic myocardial ischemia.

PMID- 21874573
TI  - Occult hip and pelvic fractures and accompanying muscle injuries around the hip.
AB  - METHOD: We investigated the incidence of occult hip and pelvic fractures and
      associated muscle injuries around the hip. PATIENTS: A total of 113 patients aged
      60-102 years with suspected hip fracture but negative plain radiographs underwent
      further examination by magnetic resonance imaging (MRI) within 2 days after an X
      ray examination. Coronal and axial T1 and T2 or short tau inversion recovery
      sequences of MRI of the hip including the sacrum were obtained. RESULTS: One
      hundred and two cases (90.2%) had bone or soft-tissue abnormalities and 83 cases
      (73.5%) had fractures of the hip and/or pelvis. The frequency of hip fracture and
      pelvic fracture was almost the same. More than half of the patients among those
      with pelvic fractures sustained occult sacral fractures; therefore, it was
      important to determine if a sacral fracture was involved when occult hip fracture
      was suspected. Muscles located at the lateral aspect of the hip, such as gluteus
      maximus, gluteus medius, gluteus minimus and quadratus femoris, were frequently
      injured in cases with intertrochanteric and greater trochanter fracture,
      suggesting that direct impact may be associated with fractures of the
      trochanteric region. However, hip rotator and adductor muscles such as obturator
      internus, obturator externus and adductor brevis were commonly injured in cases
      with pelvic fracture, indicating indirect force mediated by these muscles may be
      associated with pelvic fracture. CONCLUSION: Occult hip and pelvic fractures were
      almost equally seen among 113 cases with suspected hip fracture but were negative
      on plain radiography. Different patterns of associated muscle injuries in cases
      of occult hip fracture and pelvic fracture suggest that the mechanism of hip
      fracture and pelvic fracture is possibly different.

PMID- 21874572
TI  - Acute probiotic ingestion reduces gastrointestinal oxalate absorption in healthy
      subjects.
AB  - Both a high dietary oxalate intake and increased intestinal absorption appear to
      be major causes of elevated urine oxalate, a risk factor for kidney stone
      formation. A number of recent studies have assessed whether daily ingestion of a
      probiotic containing oxalate-degrading bacteria could lead to sufficient gut
      colonization to increase oxalate degradation, thereby reducing urinary oxalate.
      In contrast, the present study assessed whether simultaneous ingestion of oxalate
      degrading probiotic bacteria with a 176 mg oxalate load could lead to decreased
      urinary oxalate in a population of 11 healthy non-stone formers (8 females, 3
      males), aged 21-45 years. The results indicated that both the single and double
      doses of VSL#3((r)) probiotic solutions were effective in reducing urinary
      oxalate and estimated oxalate absorption with no significant difference between
      the two probiotic doses. The timing of the reduction in urinary oxalate suggested
      a small intestinal and possibly gastric reduction in oxalate absorption. Similar
      to what had been reported for chronic or daily probiotic ingestion, individuals
      characterized by high oxalate absorption were most likely to experience
      clinically significant reductions in urinary oxalate in response to acute
      probiotic ingestion.

PMID- 21874574
TI  - Closed suction drainage with or without re-transfusion of filtered shed blood
      does not offer advantages in primary non-cemented total hip replacement using a
      direct anterior approach.
AB  - INTRODUCTION: Wondering if the use of drains allowing re-transfusion of shed
      blood as opposed to closed suction drains or no drains would improve quality of
      care to patients undergoing simple non-cemented primary total hip replacement
      (THR) using a direct anterior approach, a three-arm prospective randomized study
      was conducted. METHOD: One hundred and twenty patients were prospectively
      randomized to receive no drain, closed suction drains or drains designed for re
      transfusion of shed blood. Blood loss, VAS pain scores, thigh swelling, hematoma
      formation, number of dressings changed and hospital stay were compared and
      patients followed for 3 months. RESULTS: Drains did not have any significance on
      postoperative haemoglobin and haematocrit levels or homologous blood transfusion
      rates. Patients receiving homologous blood transfusions had too small drain
      volumes to benefit from re-transfusion and patients, who get drained fluid re
      transfused, were far away from being in need of homologous blood transfusion.
      Omitting drains resulted in more thigh swelling accompanied with a tendency of
      slightly more pain during the first postoperative day but without effect on
      clinical and radiological outcome at 3 months. Earlier dry operation sites
      resulting in simplified wound care and shorter hospital stay was encountered when
      no drain was used. CONCLUSION: The possibility to re-transfuse drained blood was
      not an argument for using drains and, accepting more thigh swelling, we stop to
      use drains in simple non-cemented primary THR using the direct anterior approach.

PMID- 21874575
TI  - Clinical outcome after Chevron-Akin double osteotomy versus isolated Chevron
      procedure: a prospective matched group analysis.
AB  - BACKGROUND: Hallux valgus is a frequent condition of the forefoot, resulting in
      cosmetic deformity and pain. Chevron osteotomy (CO) is widely employed for the
      treatment of hallux valgus. Chevron-Akin double osteotomy (CAO) was previously
      described and superiority over an isolated Chevron procedure was assumed. The
      objective of this study was to compare the short-to-middle term outcomes of CO
      and CAO. PATIENTS AND METHODS: This study included 72 patients with established
      diagnosis of mild-to-moderate hallux valgus, treated by either isolated CO or
      CAO. The CO group included 46 patients (mean 51.5 years) with a mean hallux
      valgus angle of 27 degrees , while the CAO group included 26 subjects (mean 53.1
      years) and a mean hallux valgus angle of 32 degrees  preoperatively. All patients
      were reviewed by physical examination, and standardized questionnaire, and pre-
      and postoperative standing X-rays were performed. Matched group analysis was
      carried out to analyze statistical differences of both techniques. RESULTS: The
      patients were assessed and group matched at a mean of 1.37 years for the CO group
      and 1.04 years for the CAO group, postoperatively. Mean improvement of HVA
      (hallux valgus angle) was 10.6 degrees  in the CO group and the CAO group
      improved by 17.5 degrees . DMAA (distal metatarsal articular angle) improved in
      the CO group by 5.4 degrees  and in the CAO by 13.7 degrees . Mean AOFAS score
      improved by 27.9 (CO) and 21.5 (CAO). Patient satisfaction was high in both
      groups, with a tendency towards higher values within the CAO group. CONCLUSIONS:
      These findings indicate that Chevron-Akin double osteotomy is a save and
      practicable procedure for the treatment of mild-to-moderate hallux valgus.
      Superiority of combined Chevron-Akin procedure over an isolated Chevron osteotomy
      might be limited to distinct clinical settings, but should not be generally
      assumed.

PMID- 21874576
TI  - Comparison between conservative and surgical treatment in Perthes disease.
AB  - INTRODUCTION: The purpose of this study was to compare the results of
      conservative and surgical treatment in a homogeneous group constituted by
      patients between 6 and 8 years of age at onset of the Perthes disease with
      Herring B involvement. METHODS: Twenty-seven hips of 25 patients were evaluated
      radiologically and clinically. Patients were divided into two groups in terms of
      treatment type. In group I [16 hips of 14 patients], hips were treated
      conservatively using Thomas splints. The mean follow-up period was 21.5 (10-25)
      years. In group II [11 patients], hips were treated surgically using femoral
      osteotomy. The mean follow-up period was 14.3 (8-20) years. RESULTS: There was no
      statistically significant difference between the groups in terms of Stulberg
      classification, but surgically treated patients had more varus angle, more
      shortening, and more trochanteric overgrowth compared with the braced group.
      CONCLUSION: Non-surgical treatment with a brace is a reliable alternative to
      surgical treatment in Perthes disease between 6 and 8 years of age at onset with
      Herring B involvement. However, we could not know whether the good results were
      influenced by the brace or stemmed from having good prognosis of these patients.

PMID- 21874577
TI  - Cup positioning in total hip arthoplasty: spatial alignment of the acetabular
      entry plane.
AB  - PURPOSE: Correct cup positioning is one of the keys for successful total hip
      replacement. There are mechanical and computer assistant guides for correct cup
      positioning in the market. To optimize the cup positioning, the use of navigation
      systems is recommended. The aim of this study was to compare spatial orientation
      of the acetabulary entry plane in relation to tables plane which is used by
      mechanical guides as well as anterior pelvic plane used for cup orientation by
      navigation systems. METHODS: CT raw data of 80 Caucasians (160 acetabuli) (done
      in supine position) with osteoartritic hips were collected. 3-D pelvic
      reconstruction was generated using Amira software (Visage Imaging Berlin,
      Germany). Anterior pelvic plane and acetabulary entry plane were defined by
      reliable anatomical landmarks. Spatial orientation were calculated by a custom
      made program code for the Amira software. RESULTS: There were no differences
      between anterior pelvic plane and table's plane as well as spatial orientation of
      acetabulary entry plane of both acetabuli in relation to anterior pelvic plane or
      table's plane. Furthermore, there was no correlation between age, sex or body
      mass index and spatial orientation of the acetabulary entry plane as well.
      CONCLUSIONS: The use of mechanical alignment guides for cup orientation during
      total hip arthroplasty based on table's plane in patient's supine position is a
      successful method to achieve proper cup orientation.

PMID- 21874578
TI  - I. In vivo evidence for partial agonist effects of (-)-OSU6162 and (+)-OSU6162 on
      5-HT2A serotonin receptors.
AB  - The locomotor effects of (-)- and (+)-OSU6162 were evaluated in 'low activity'
      animals (reserpinized mice and habituated rats) and 'high activity' animals (drug
      naive mice and non-habituated rats). Both enantiomers of OSU6162 had dual effects
      on behavior, stimulating locomotor activity in 'low activity' animals and
      inhibiting locomotor activity in 'high activity' animals. There were also certain
      differences between the two enantiomers in their behavioral profiles. The
      stimulatory effects of both enantiomers in reserpinized mice were blocked by the
      5-HT2A selective antagonist M100907, but not by the D2-selective antagonists
      haloperidol or raclopride, or by the D1-selective antagonists SCH23390 or
      SCH39166. The stimulatory effect in mice was more pronounced for (+)- than for (
      )-OSU6162. In drug-naive mice, both enantiomers of OSU6162 produced head
      twitches, albeit to a much lesser extent than DOI, and both enantiomers inhibited
      DOI-induced head twitches, the (-)-form more effectively so than the (+)-form.
      These results suggest that (-)- and (+)-OSU6162 are partial agonists on 5-HT2A
      receptors and that the (+)-form has a higher intrinsic activity than the (-)
      form. At high doses, both enantiomers inhibited locomotor activity in drug-naive
      mice, with (-)-OSU6162 being more potent than (+)-OSU6162. Similarly, in high
      active rats, both enantiomers inhibited locomotor activity, with the (-)
      enantiomer being more potent than the (+)-enantiomer. Conversely, in habituated
      rats, both enantiomers stimulated locomotor activity, and here, as opposed to the
      case in low-active mice, (-)-OSU6162 was more effective than (+)-OSU6162. The
      stimulatory effects in habituated rats of both enantiomers could be antagonized
      with either haloperidol or M100907. Overall, these results indicate that the dual
      effects on behavior of (-)- and (+)-OSU6162 are mediated through D2 and 5-HT2A
      receptors, consistent with their in vitro functional selectivity profiles (see
      Burstein et al., accompanying paper). Thus, both enantiomers of OSU6162 seem to
      act as stabilizers not only on dopaminergic, but also on serotonergic brain
      signaling. These discoveries have important implications for the potential
      clinical utility of both compounds, as well as for several of their congeners.

PMID- 21874579
TI  - Pilot study on HTR2A promoter polymorphism, -1438G/A (rs6311) and a nearby copy
      number variation showed association with onset and severity in early onset
      obsessive-compulsive disorder.
AB  - A previous study showed that a single nucleotide polymorphism (SNP), -1438G/A
      (rs6311), found in the transcriptional control region of the gene that encodes
      the serotonin-receptor 2A (HTR2A) was associated with obsessive-compulsive
      disorder (OCD) in a sample of children and adolescents. In this study, we
      reanalyzed the association of this SNP with OCD in an enlarged population of 136
      cases (55 previous + 81 new cases) and compared them to 106 newly recruited,
      healthy, age-matched controls. We also investigated whether this SNP or its copy
      number variations (CNV) was associated with OCD severity and age of onset. The
      CNV was analyzed in a DNA region located near rs6311. The results confirmed the
      association between the A-allele and early onset OCD in children and adolescents,
      with an odds ratio (OR) of 1.69 [95% CI (1.17, 2.46); p = 0.005]. Strikingly, we
      found that carriers of one copy (deletion) of the CNV were associated with a very
      early onset OCD (2.5 years earlier than the typical onset), and they had
      increased CY-BOCS scores (8.7 points higher compared to "normal" CNV and
      duplications); which is related to increased severity of OCD symptoms (p = 0.031;
      p = 0.004, respectively). Compared to the normal CNV and duplications, the
      association between the deletion and OCD showed an OR of 7.56 [95% CI (1.32,
      142.84); p = 0.020]. These results pointed to the functional importance of this
      promoter region of HTR2A; it influenced the occurrence, the onset, and the
      severity of OCD.

PMID- 21874580
TI  - Lifestyle characteristics assessment of Japanese in Pittsburgh, USA.
AB  - Lifestyle-related chronic diseases such as cancer and cardiovascular disease are
      the greatest public health concerns. Evidence shows Japanese immigrants to a
      westernized environment have higher incidence of lifestyle-related diseases.
      However, little is known about lifestyle characteristics related to chronic
      diseases for Japanese in a westernized environment. This study is examining the
      gap in lifestyle by comparing the lifestyle prevalence for Japanese in the US
      with the Japanese National Data (the National Health and Nutrition Survey in
      Japan, J-NHANS) as well as the Japan National Health Promotion in the twenty
      first Century (HJ21) goals. Japanese adults were surveyed in Pittsburgh, USA,
      regarding their lifestyle (e.g., diet, exercise, smoking, stress, alcohol, and
      oral hygiene). The prevalence was compared with J-NHANS and HJ21 goals. Ninety
      three responded (response rate; 97.9%). Japanese men (n = 38) and women (n = 55)
      in Pittsburgh smoke less than Japanese in Japan (P < 0.001 for both genders).
      Japanese in Pittsburgh perform less physical activity in daily life and have
      lower prevalence of walking more than 1 h per day (P < 0.001 for both genders).
      Japanese women in Pittsburgh have significantly higher prevalence of stress than
      in Japan (P = 0.004). Japanese men in Pittsburgh do not reach HJ21 goal in weight
      management, BMI, use of medicine or alcohol to sleep, and sleep quality. Japanese
      women in Pittsburgh do not reach HJ21 goal in weight management and sleep
      quality. In conclusion, healthy lifestyle promotion including exercise and
      physical activity intervention for Japanese living in a westernized environment
      is warranted.

PMID- 21874581
TI  - Community associated methicillin resistant Staphylococcus aureus among New York
      City men who have sex with men: qualitative research findings and implications
      for public health practice.
AB  - Academic literature has recorded increased microbial resistance in the United
      States and recent news media has adversely portrayed men who have sex with men
      (MSM) at increased risk for community associated methicillin resistant
      Staphylococcus aureus (CA-MRSA) transmission. CA-MRSA is a specific type of
      bacteria resistant to certain antibiotics, which limits treatment options for
      those needing clinical care. Infection can manifest as painful abscesses and can
      cause severe illness. With increased CA-MRSA infections overall, and attention
      given to MSM populations regarding CA-MRSA, as well as the fact that limited data
      on sociocultural factors that may facilitate transmission, we undertook a
      qualitative study to explore contextual influences that may fuel infection among
      MSM in New York City so that public health professionals can better recognize,
      and respond appropriately to, potential future outbreaks. In-depth interviews
      were used to qualitatively investigate perceptions and beliefs regarding
      transmission, as well as community understandings of treatment options.
      Participants included thirteen MSM who reported a previous CA-MRSA infection and
      nine community practitioners. A thematic content analysis of these interviews was
      conducted and data suggests that behaviors and exposures associated with
      transmission of CA-MRSA are common in certain MSM networks. Specifically,
      sociocultural influences and methamphetamine use activities were found to
      contribute to CA-MRSA transmission. We underscore the role of public health and
      health services practitioners in providing appropriate CA-MRSA awareness and
      education to MSM populations.

PMID- 21874582
TI  - Taking our own medicine: on an experiment in science communication.
AB  - In 2007 a social scientist and a designer created a spatial installation to
      communicate social science research about the regulation of emerging science and
      technology. The rationale behind the experiment was to improve scientific
      knowledge production by making the researcher sensitive to new forms of reactions
      and objections. Based on an account of the conceptual background to the
      installation and the way it was designed, the paper discusses the nature of the
      engagement enacted through the experiment. It is argued that experimentation is a
      crucial way of making social science about science communication and engagement
      more robust.

PMID- 21874583
TI  - [Leishmania infantum MON-1 isolated from a golden jackal (Canis aureus) in Grande
      Kabylie (Algeria)].
AB  - In the north of Algeria, Leishmania infantum is responsible for two clinical
      forms of leishmaniasis: visceral and cutaneous leishmaniasis, for which dogs are
      the only proven reservoir host. In this study, the authors report, for the first
      time, the isolation of L. infantum from a golden jackal (Canis aureus) trapped in
      the Illoulen ou Malou region (Grande Kabylie). Two isolates were thus obtained
      from bone marrow and spleen and were identified by starch gel isoenzyme
      electrophoresis as L. infantum MON-1, the widespread zymodeme in the north of the
      country. Leishmania parasites have also been detected by polymerase chain
      reaction (PCR) in the biopsy of the spleen. The golden jackal, a prevalent wild
      canid in Northern Africa, could play a predominant role in the sylvatic foci of
      leishmaniasis and in the dissemination of the parasite in this region.

PMID- 21874584
TI  - VP22 enhances the expression of glucocerebrosidase in human Gaucher II fibroblast
      cells mediated by lentiviral vectors.
AB  - Gaucher disease is an autosomal recessive lysosomal storage disorder resulting in
      a deficiency of glucocerebrosidase (GC). Imiglucerase, a recombinant form of GC,
      has been successfully used in the treatment of Gaucher disease and has been shown
      to be a good potential candidate for gene therapy. However, its low transduction
      efficiency and short duration of expression have limited it as a gene therapy
      strategy. VP22, the herpes simplex virus type I tegument protein, is known to
      facilitate intercellular protein transport, thus making it a promising tool for
      improving gene transfer efficiency. To investigate whether the fusion of VP22 to
      GC could improve its therapeutic efficiency for Gaucher disease, the lentiviral
      vectors pHIV-GC and pHIV-VP(22)-GC were constructed and confirmed by PCR or RT
      PCR. After packaging, the vectors were transduced into human Gaucher II
      fibroblast cells (GII cells). Flow cytometric analysis revealed that the GC
      expression rates in lenti-VP(22)-GC-transduced GII cells were higher by
      comparison than those in lenti-GC-transduced GII cells. A Western blot
      demonstrated higher levels of GC protein expression in lenti-VP(22)-GC-transduced
      GII cells. In addition, the long-term expression levels and increased GC
      activities in lenti-VP(22)-GC-transduced GII cells were also observed. These data
      implicate that VP22-mediated effects may be useful for enhancing the efficacy of
      this Gaucher disease treatment.

PMID- 21874585
TI  - Effect of thiazides on bone mineral density in children with idiopathic
      hypercalciuria.
AB  - To determine the effect of thiazide treatment on bone mineral density (BMD) in
      children with idiopathic hypercalciuria (IH) and osteopenia, we reviewed the case
      notes of 22 children aged 11.7 +/- 2.7 years diagnosed with IH and osteopenia who
      had received thiazides for 2.4 years. The data on this group were compared with
      those of 32 IH children with osteopenia aged 11.2 +/- 2.7 years who had not
      received thiazide treatment. By the end of the follow-up period, the z-BMD had
      improved spontaneously in 23 of the 32 control children (72%) and in 12 of the 22
      patients on thiazides (54%). Although treated patients had a higher body mass
      index (BMI) and a higher BMD following treatment, the differences became
      statistically negligible when these parameters were expressed as z-BMD or as bone
      mineral apparent density (BMAD). In contrast, within the control group, there
      were significant differences in BMAD and z-BMD at the end of the follow-up.
      Patients who had an improved z-BMD at the end of the treatment also showed an
      increase in their BMI. Based on these results, we conclude that thiazide
      treatment does not improve the z-BMD in children with IH. More than half of the
      children suffering from IH enrolled in our study showed a spontaneous improvement
      in their z-BMD, which was more evident when the initial BMAD was not low and when
      their BMI increased during the follow-up period.

PMID- 21874587
TI  - G6PD genotype and its associated enzymatic activity in a Chinese population.
AB  - Knowledge of the G6PD genotype and its associated enzyme activity is significant
      for population genetics, diagnosis of disease, and management of patients. We
      tested 2,872 unrelated subjects from a Hakka population in China for G6PD
      activity by the WHO standard method and for genotype by DHPLC and DNA sequencing.
      Among female heterozygotes, 78.5% had relatively normal enzyme activity. The
      phenotype frequency of G6PD deficiency is 0.028, and the causal allele frequency
      is 0.060 in females. The accuracy, sensitivity, and specificity of DHPLC are more
      than 98% for detecting G6PD-deficient hemizygotes, heterozygotes, and
      homozygotes. Measuring enzyme activity alone is not sufficient for the diagnosis
      of heterozygotes. A combination of enzyme activity and DNA analysis should be
      used.

PMID- 21874586
TI  - Nutrition in infants and very young children with chronic kidney disease.
AB  - Provision of adequate nutrition is a cornerstone of the management of infants and
      very young children with chronic kidney disease (CKD). Very young children with
      CKD frequently have poor spontaneous nutritional intake. Because growth depends
      strongly on nutrition during early childhood, growth in very young children with
      CKD is often suboptimal. In this review we will consider the mechanisms and
      manifestations of inadequate nutritional status in very young children with CKD,
      mechanisms mediating inadequate nutritional intake, and the optimal nutritional
      management of this special population. In addition, we suggest an approach to the
      assessment of nutritional status, including the use of body mass index in
      infants. Five major nutritional components are considered: energy,
      macronutrients, fluids and electrolytes, micronutrients, and
      calcium/phosphorus/vitamin D. The use of adjunctive therapies, including appetite
      stimulants, treatment of gastroesophageal reflux and gastric dysmotility,
      enhanced dialytic clearance, and growth hormone, is also briefly discussed.

PMID- 21874588
TI  - Cloning and identification of microRNAs in earthworm (Eisenia fetida).
AB  - MicroRNAs (miRNAs) (noncoding RNAs of 20-25 nucleotides) play important roles in
      the post-transcriptional regulation of gene expression in various eukaryotes and
      prokaryotes. Piwi-interacting RNAs function by combining with PIWI proteins to
      regulate protein synthesis and to stabilize mRNA, the chromatin framework, and
      genome structure. This study investigates the role of miRNAs in regeneration. A
      scrDNA library was constructed, and 17 noncoding RNAs from Eisenia fetida (an
      optimal model for the study of earthworm regeneration) were cloned and
      characterized. In addition, reverse transcription polymerase chain reaction was
      performed to analyze the expression of four small RNAs during different
      developmental stages. The expression levels of these RNAs in regenerating tissue
      were higher than in normal tissue, and the expression patterns of these small
      RNAs were unique during development.

PMID- 21874590
TI  - Inhibition of intercellular adhesion in herpex simplex virus infection by
      glycyrrhizin.
AB  - Herpes simplex virus (HSV) is one of the most common viruses infecting humans and
      animals. Cellular adhesion is increased in HSV and plays a role in pathogenesis
      of inflammatory response during this viral infection. In our study, we studied a
      potential role of glycyrrhizin in disrupting cellular adhesion in HSV. We
      isolated rat cerebral capillary vessel endothelial cells (CCECs) and
      polymorphonuclear leukocytes (PMN) and evaluated intercellular adhesion between
      these cells by micropipette aspiration technique. The adhesion force and stress
      between CCEC and PMN were significantly (P < 0.01) increased in HSV infection.
      Glycyrrhizin perfusion significantly (P < 0.01) reduced adhesion force and stress
      between CCEC and PMN. In conclusion, glycyrrhizin may attenuate inflammatory
      responses in HSV by inhibition of adhesion between CCEC and PMN.

PMID- 21874589
TI  - Escherichia coli diversity in livestock manures and agriculturally impacted
      stream waters.
AB  - Escherichia coli (E. coli) isolate diversity enhances the likelihood of survival,
      spread, and/or transmission of the organism among environments. Understanding the
      ecology of this important organism is requisite for development of more accurate
      protocols for monitoring and regulatory purposes. In this study, E. coli
      diversity, gene profiles and transport properties of isolates from different
      livestock and water sources were evaluated. Strain diversity was evaluated by BOX
      PCR, phylotyping, and profiling for 15 genes associated with adhesion, toxin
      production, iron acquisition or capsular synthesis. Attachment efficiencies were
      calculated for 17 isolates following transport through saturated porous media.
      Richness of genotype profiles for livestock isolates was relatively low (25, 12,
      and 11 for swine, poultry and dairy, respectively) compared to those from stream
      water (115 and 126 from dry or wet weather events, respectively). Attachment
      efficiencies varied by an order of magnitude (0.039-0.44) and the isolate with
      the highest attachment efficiency possessed the largest suite of targeted genes
      including those for adherence (iha, agn43, and fimH), surface exclusion (traT)
      and the siderophore iroN ( E.coli ). Variation in E. coli isolates based on
      temporal and ecological source was found to translate to equally broad ranges in
      transport efficiency underscoring the large degree of genotypic and phenotypic
      variation that exists among E. coli isolates. The impact of this diversity on
      genetic exchange and the concomitant effect on the organisms' fate and transport
      under in situ environmental conditions warrant further investigation. These
      factors also require careful consideration for purposes of modeling, source
      tracking, and risk assessment.

PMID- 21874591
TI  - Clinical features of 405 Japanese patients with systemic sclerosis.
AB  - We aimed to clarify the clinical features of Japanese patients with systemic
      sclerosis (SSc), especially with reference to organ involvement and
      autoantibodies. A cohort of 405 patients with SSc who attended our institution
      from 1973 to 2008 was identified retrospectively. Data on clinical features,
      including autoantibodies, organ involvement, and overlap of other connective
      tissue diseases, were obtained by following the medical records until 2009. The
      percentage of male patients during or after 1990 was greater than that before
      1990 (3.9 vs. 10.6%, respectively). Limited cutaneous SSc (lSSc) was twice as
      frequent as diffuse cutaneous SSc (dSSc). About half of the patients had lung
      involvement (50.4%), while only 3.2% had scleroderma renal crisis. Male gender
      was associated with lung involvement, and dSSc was associated with most organ
      involvements except for pulmonary arterial hypertension (PAH). Anti-Scl-70
      antibody was associated with lung or heart involvement, while anti-U1-RNP
      antibody was only associated with PAH. Conversely, patients with anti-centromere
      antibody had less organ involvement. SSc-Sjogren overlap syndrome was related to
      lSSc, further overlapping systemic lupus erythematosus (SLE), and less lung or
      heart involvement. In conclusion, these results not only confirmed previous
      reports but revealed several other findings, such as the increased proportion of
      male patients in recent years and the relationships between clinical features.

PMID- 21874592
TI  - The localization of Tic20 proteins in Arabidopsis thaliana is not restricted to
      the inner envelope membrane of chloroplasts.
AB  - Tic20 is a central, membrane-embedded component of the precursor protein
      translocon of the inner envelope of chloroplasts (TIC). In Arabidopsis thaliana,
      four different isoforms of Tic20 exist. They are annotated as atTic20-I, -II, -IV
      and -V and form two distinct phylogenetic subfamilies in embryophyta. Consistent
      with atTic20-I being the only essential isoform for chloroplast development, we
      show that the protein is exclusively targeted to the chloroplasts inner envelope.
      The same result is observed for atTic20-II. In contrast, atTic20-V is localized
      in thylakoids and atTic20-IV dually localizes to chloroplasts and mitochondria.
      These results together with the previously established expression profiles
      explain the recently described phenotypes of Tic20 knockout plants and point
      towards a functional diversification of these proteins within the family. For all
      Tic20 proteins a 4-helix topology is proposed irrespective of the targeted
      membrane, which in part could be confirmed in vivo by application of a self
      assembling GFP-based topology approach. By the same approach we show that the
      inner envelope localized Tic20 proteins expose their C-termini to the chloroplast
      stroma. This localization would be consistent with the positive inside rule
      considering a stromal translocation intermediate as discussed.

PMID- 21874593
TI  - Modeling relationships between traditional preadmission measures and clinical
      skills performance on a medical licensure examination.
AB  - Medical schools employ a variety of preadmission measures to select students most
      likely to succeed in the program. The Medical College Admission Test (MCAT) and
      the undergraduate college grade point average (uGPA) are two academic measures
      typically used to select students in medical school. The assumption that
      presently used preadmission measures can predict clinical skill performance on a
      medical licensure examination was evaluated within a validity argument framework
      (Kane 1992). A hierarchical generalized linear model tested relationships between
      the log-odds of failing a high-stakes medical licensure performance examination
      and matriculant academic and non-academic preadmission measures, controlling for
      student-and school-variables. Data includes 3,189 matriculants from 22
      osteopathic medical schools tested in 2009-2010. Unconditional unit-specific
      model expected average log-odds of failing the examination across medical schools
      is -3.05 (se = 0.11) or 5%. Student-level estimated coefficients for MCAT Verbal
      Reasoning scores (0.03), Physical Sciences scores (0.05), Biological Sciences
      scores (0.04), uGPA(science) (0.07), and uGPA(non-science) (0.26) lacked
      association with the log-odds of failing the COMLEX-USA Level 2-PE, controlling
      for all other predictors in the model. Evidence from this study shows that
      present preadmission measures of academic ability are not related to later
      clinical skill performance. Given that clinical skill performance is an important
      part of medical practice, selection measures should be developed to identify
      students who will be successful in communication and be able to demonstrate the
      ability to systematically collect a medical history, perform a physical
      examination, and synthesize this information to diagnose and manage patient
      conditions.

PMID- 21874594
TI  - Feasibility of self-reflection as a tool to balance clinical reasoning
      strategies.
AB  - Clinicians are believed to use two predominant reasoning strategies: system 1
      based pattern recognition, and system 2 based analytical reasoning. Balancing
      these cognitive reasoning strategies is widely believed to reduce diagnostic
      error. However, clinicians approach different problems with different reasoning
      strategies. This study explores whether clinicians have insight into their
      problem specific reasoning strategy, and whether this insight can be used to
      balance their reasoning and reduce diagnostic error. In Experiment 1, six medical
      residents interpreted eight ECGs and self-reported their predominant reasoning
      strategy using a four point scale (4S). Self-assessed reasoning strategy
      correlated with objective assessment by two clinical experts using a post hoc
      talk-aloud protocol (rho = 0.69, p < 0.0001). Reporting an analytic strategy was
      also associated with 40% longer interpretation times (p = 0.01). In Experiment 2,
      twenty-four residents were asked to reinterpret eight ECGs with instructions
      customized to their 4S. Half of the ECGs were reinterpreted with instructions to
      use the opposite reasoning strategy to that reported, and half with instructions
      to use the same reasoning strategy. ECG reinterpretation scores did not differ
      with potentiating compared to balancing reasoning instructions (F(1,188) = 0.22,
      p = 0.64). However, analytic instructions were associated with improved scores
      (F(1,188) = 15, p < 0.0001). These data suggest that clinicians are able to
      recognize their reasoning strategies. However, attempting to balance reasoning
      strategies through customizable instructions did not result in a reduction in
      diagnostic errors. This suggests important limitations to the widespread belief
      in balancing reasoning strategies to reduce diagnostic error.

PMID- 21874595
TI  - Molecular characterization of Staphylococcus pseudintermedius strains isolated
      from clinical samples of animal origin.
AB  - The aim of this study was to determine the species distribution among 44 randomly
      selected clinical isolates (30 mecA-positive and 14 mecA-negative) of animal
      origin previously identified as Staphylococcus intermedius by phenotypic tests
      and species-specific PCR amplification of the 16S rRNA gene. For this purpose, we
      used a multiplex PCR for the detection of the nuc gene and restriction fragment
      length polymorphism analysis of pta gene amplified by PCR. Both methods allow
      discrimination of Staphylococcus pseudintermedius from the other closely related
      members of the S. intermedius group and other coagulase-positive staphylococci
      isolated from animals. Genetic diversity of S. pseudintermedius strains was
      analyzed by staphylococcal protein A-encoding gene (spa) typing. Multiplex PCR
      method was used to identify staphylococcal cassette chromosome mec (SCCmec) type
      in mecA-positive strains. All isolates previously identified as S. intermedius
      were shown to belong to S. pseudintermedius. According to PCR-based SCCmec
      typing, SCCmecIII was the most prevalent type (n = 23), and solely seven isolates
      were designated as non-typeable. Furthermore, the assessment of spa-typing
      results revealed that the majority of all strains (n = 27) harbored spa type t02,
      and 17 strains were classified as non-typeable.

PMID- 21874596
TI  - Phylogenetic analysis of urease-positive thermophilic Campylobacter (UPTC)
      strains based on the molecular characterization of the flaA gene.
AB  - Molecular cloning, nucleotide sequencing, and characterization of the flaA gene
      from additional isolates of urease-positive thermophilic Campylobacter (UPTC)
      were performed. These isolates were obtained from the natural environment in
      Northern Ireland (n = 9 from mussels) and in England (n = 1 from sea water). All
      isolates carried the shorter flaA gene, [open reading frames (ORFs), 1,461 to
      1,503 base pairs], without any internal termination codons, and did not carry any
      flaA pseudogenes. The UPTC isolates were well discriminated by the neighbor
      joining (NJ) phylogenetic tree constructed based on the putative flaA genes ORFs
      nucleotide sequence information. In addition, the NJ tree constructed based on
      the flaA-short variable region sequence information discriminated the
      Campylobacter lari isolates with a similar degree of discrimination power.

PMID- 21874598
TI  - Implementing an evidence-based parenting program in community agencies: what
      helps and what gets in the way?
AB  - Adoption of evidence-based programs for families by community agencies requires
      an understanding of variables that influence implementation. Managers and service
      providers from 64 community agencies reported on variables that affected the
      implementation of Triple P, an evidence-based parenting program. Both types of
      stakeholders reported adequate office resources; over half the managers and over
      two-thirds of service providers reported adequate training. Adequate office
      resources and positive agency characteristics, including organizational climate,
      were associated with higher program usage. Service providers' reports of the
      variables impacted their individual adherence rates; managers had broader
      perspectives of the quality of implementation in their organizations.

PMID- 21874597
TI  - Novel approaches to treating leptomeningeal metastases.
AB  - Leptomeningeal metastasis is a devastating complication of the central nervous
      system in patients with late-stage solid or hematological cancers. Leptomeningeal
      metastasis results from the multifocal seeding of the leptomeninges by malignant
      cancer cells. Although central nervous system metastasis usually presents in
      patients with widely disseminated and progressive late-stage cancer, malignant
      cells may spread to the cerebrospinal fluid during earlier disease stages in
      particularly aggressive cancers. Treatment of leptomeningeal metastasis is
      largely palliative but will often provide stabilization and protection from
      further neurological deterioration and improve quality of life. There is a need
      to raise awareness of the impact of leptomeningeal metastases on cancer patients
      and its known and putative biological basis. Novel diagnostic approaches include
      identification of biomarkers that may stratify the risk for developing
      leptomeningeal metastasis. Current therapies can be used more effectively while
      waiting for advanced treatments to be developed.

PMID- 21874599
TI  - Effects of marsh pond terracing on coastal wintering waterbirds before and after
      Hurricane Rita.
AB  - From February to March 2005-2006, we surveyed wintering waterbirds to test
      effects of terracing on coastal pond use before and after Hurricane Rita. Marsh
      terracing is intended to slow coastal marsh loss in the Chenier Plain by slowing
      marsh erosion and encouraging vegetation expansion. Terraces also increase marsh
      edge in ponds, possibly benefiting waterbirds. We monitored paired terraced and
      unterraced ponds in three sites within southwestern Louisiana's Chenier Plain.
      Waterbirds were 75% more numerous in terraced than unterraced ponds. Waterbird
      richness was similar among ponds when corrected for number of individuals,
      suggesting terracing increased bird density but did not provide habitat unique
      from unterraced ponds. Birds were 93% more numerous following Hurricane Rita,
      mostly due to an influx of migrating waterfowl. Year round residents were similar
      in number before and after Hurricane Rita. Resident richness did not differ among
      years after correcting for number of observed individuals. Wading and dabbling
      foragers were more abundant in terraced ponds and these two guilds represented
      74% of birds observed. We detected no difference among ponds for other guilds,
      i.e., probing, aerial, and diving foragers. Increasing proportion of mash edge
      increased bird density disproportionately: On average ponds with 10% edge had 6
      birds observed and ponds with 30% edge had 16 birds observed. Terraces increased
      habitat interspersion and were an effective tool for increasing numbers of
      wintering waterfowl and wading birds. The extent to which terraces were
      sustainable following hurricane forces is unknown.

PMID- 21874600
TI  - Seasonal changes in body mass, energy intake and thermogenesis in Maximowiczi's
      voles (Microtus maximowiczii) from the Inner Mongolian grassland.
AB  - Small mammals inhabiting temperate and arctic regions exhibit annual adaptive
      adjustments in physiology, anatomy, and behavior. No data on the physiology of
      Maximowicz's voles (Microtus maximowiczii) are available at present. Here we
      examined the seasonal changes in body mass, food intake, thermogenic capacity,
      serum leptin and thyroid hormone levels in wild-captured individuals from Inner
      Mongolian grassland, China. We further examined the effects of photoperiod on
      these parameters. Energy intake, resting metabolic rate, nonshivering
      thermogenesis (NST), and serum tri-iodothyronine (T3) levels increased while
      serum leptin and body mass decreased in the cold seasons. Serum T3 levels were
      positively correlated with NST and uncoupling protein 1 (UCP1) contents in brown
      adipose tissue, and leptin levels were negatively correlated with energy intake
      and resting metabolic rate. Furthermore, laboratory data showed these changes
      could be induced by short photoperiod alone. Taken together, our results indicate
      that Maximowicz's voles can increase thermogenic capacity and energy intake to
      cope with cold stress. Serum leptin seems to be involved in the regulation of
      energy intake and changes in T3 level may be important for the variations in NST
      and/or UCP1. Short photoperiod can serve as a seasonal cue for the winter
      acclimatization of energy balance in free-living Maximowicz's voles.

PMID- 21874601
TI  - Flow and volume dependence of rat airway resistance during constant flow
      inflation and deflation.
AB  - STUDY OBJECTIVES: The aim of this study was to measure the flow and volume
      dependence of both the ohmic and the viscoelastic pressure dissipations of the
      normal rat respiratory system separately during inflation and deflation. METHOD:
      The study was conducted in the Respiratory Physiology Laboratory in our
      institution. Measurements were obtained for Seven albino Wistar rats of both
      sexes by using the flow interruption method during constant flow inflations and
      deflations. Measurements included anesthesia induction, tracheostomy and
      positioning of a tracheal cannula, positive pressure ventilation, constant flow
      respiratory system inflations and deflations at two different volumes and flows.
      RESULTS: The ohmic resistance exhibited volume and flow dependence, decreasing
      with lung volume and increasing with flow rate, during both inflation and
      deflation. The stress relaxation-related viscoelastic resistance also exhibited
      volume and flow dependence. It decreased with the flow rate at a constant lung
      volume during both inflation and deflation, but exhibited a different behavior
      with the lung volume at a constant flow rate (i.e., increased during inflations
      and decreased during deflations). Thus, stress relaxation in the rat lungs
      exhibited a hysteretic behavior. CONCLUSIONS: The observed flow and volume
      dependence of respiratory system resistance may be predicted by an equation
      derived from a model of the respiratory system that consists of two distinct
      compartments. The equation agrees well with the experimental data and indicates
      that the loading time is the critical parameter on which stress relaxation
      depends, during both lung inflation and deflation.

PMID- 21874602
TI  - Cue-switch effects do not rely on the same neural systems as task-switch effects.
AB  - The cued task-switching paradigm is often used to study cognitive control. In
      this paradigm, people are generally slower and make more errors when switching
      tasks as compared with repeating the same task. When two cues are mapped to each
      task, these switch costs could result from a mixture of cue-switch effects (which
      are thought to reflect cue encoding) and task-switch effects (which are thought
      to reflect task set preparation). In the behavioral literature, there has been a
      lively debate on the degree to which cue-switch effects and task-switch effects
      indeed reflect different phenomena. In the present study, we used fMRI to examine
      whether and to what extent the neural network underlying task-switch effects is
      also involved in cue-switch effects. We found task-switch but no cue-switch
      effects in the frequently observed preparation-related activation in fronto
      parietal areas. These results suggest that the fronto-parietal areas displaying
      preparatory activity in task-switching paradigms are engaged in task preparation
      but not in cue encoding and that task preparation and cue encoding rely on
      completely different processes.

PMID- 21874603
TI  - Understanding population-based site-specific cancer incidence rates in the USA.
AB  - As compared with conventionally reported national population-based incidence
      rates, incidence rates better represent the "burden" of disease if they remove
      prevalent cases from the denominator. In order to reflect the "risk" in a disease
      free population, rates should both exclude prevalent cases from the denominator
      and second or later diagnosed cases at the same site from the numerator. Five
      common cancers were evaluated through a correction method using 2005-2007
      Surveillance, Epidemiology, and End Results Program data to determine the extent
      of difference between conventional and corrected incidence rates. These
      corrections lowered the incidence rates 4.0-5.8% for female breast cancer, 4.6
      7.6% for melanoma, 3.0-4.0% for colorectal cancer, and 2.1-2.5% for lung and
      bronchus cancer. Corrected incidence rates for prostate cancer were 9.9-13.7%
      higher. In cancers with either high prevalence and/or high occurrence of multiple
      primaries at the same site, corrected population-based incidence rates are
      warranted.

PMID- 21874604
TI  - Symptoms of sleep apnoea in chronic heart failure--results from a prospective
      cohort study in 1,500 patients.
AB  - BACKGROUND: In patients with chronic heart failure, sleep-disordered breathing
      (SDB) is a common co-morbidity worsening prognosis. The aim of this study was to
      investigate whether assessment of specific symptoms can elucidate presence of SDB
      in these patients. METHODS: A prospective questionnaire scoring investigation on
      possible symptoms of sleep apnoea (nocturia, fatigue, daytime sleepiness,
      snoring, nocturnal sweating, witnessed apnoea's, nap) was conducted in 1,506
      consecutive patients with stable chronic heart failure (LVEF <=45%, NYHA >=2).
      Afterwards, polysomnography or polygraphy, capillary blood gas analysis,
      echocardiography, and cardiopulmonary exercise testing were performed. RESULTS:
      Adjusted for all significant covariates, snoring (p < 0.01) was the only symptom
      independently associated with OSA, while witnessed apnoeas (p = 0.02) and fatigue
      (p = 0.03) independently predicted for CSR. As additional parameters, higher BMI
      (threshold 26.6; p < 0.01) and higher pCO(2) (threshold 37.6 mmHg; p < 0.01) were
      independently associated with OSA and male gender (p < 0.001) and lower pCO(2)
      (threshold 35.0 mmHg; p < 0.001) with CSA. Cumulative questionnaire score results
      did not sufficiently (OSA--sensitivity 0.40, specificity 0.74; CSA--sensitivity
      0.57, specificity 0.59) predict SDB. CONCLUSION: Although in chronic heart
      failure patients with either OSA or CSA specific symptoms are apparent, combining
      clinical data, demographic data, and capillary blood gas analysis results appears
      favourable to determine the presence of SDB.

PMID- 21874605
TI  - Spiritual wellbeing mediates PTSD change in veterans with military-related PTSD.
AB  - BACKGROUND: A portable practice of repeating a mantram-a sacred word or phrase
      has been shown to reduce the severity of posttraumatic stress disorder (PTSD)
      symptoms in veterans with military trauma. It is thought that the intervention re
      directs attention and initiates relaxation to decrease symptom severity, but
      there may be other mechanisms that may contribute to this improvement. PURPOSE:
      We tested the hypothesis that increases in existential spiritual wellbeing (ESWB)
      would mediate reductions in self-reported PTSD symptoms following a group mantram
      intervention. METHOD: Veterans diagnosed with PTSD from war-related trauma
      completed 6 weeks of case management plus a group mantram intervention (n = 66)
      as part of a randomized trial. Measures included PTSD Checklist (PCL) and
      Functional Assessment of Chronic Illness Therapy-Spiritual Wellbeing. Path
      analysis was conducted on those who completed treatment to assess ESWB as a
      possible mediator of change in PCL from baseline to post-treatment. RESULTS: A
      significant indirect effect, -2.24, 95% CI (-4.17, -1.05) of the mantram
      intervention on PCL change was found. The path from the mantram intervention to
      ESWB change was significant and positive (B = 4.89, p < 0.0001), and the path
      from ESWB change to PCL change was significant and negative (B = -0.46, p =
      0.001), thus supporting the hypothesis. CONCLUSIONS: Findings suggest that one
      contributing mechanism that partially explains how the mantram intervention
      reduces PTSD symptom severity in veterans may be by increasing levels of ESWB.

PMID- 21874606
TI  - Identification of bla KPC-2 on different plasmids of three Morganella morganii
      isolates.
AB  - Three Morganella morganii strains resistant to carbapenems were recovered from
      the surgical intensive care unit (SICU) in our hospital. Carbapenemases and
      extended-spectrum beta-lactamases (ESBLs) were respectively detected by the
      modified Hodge test and the modified Clinical and Laboratory Standards Institute
      (CLSI) ESBL confirmatory test in all isolates. Amplification of whole-cell and
      plasmid DNAs extracted from isolates with primers specific for the bla (KPC)
      produced an amplicon confirmed to be bla (KPC-2) by sequence analysis. Pulsed
      field gel electrophoresis (PFGE) typing revealed that three isolates belonged to
      two closely related types. Plasmids electrophoresis and restriction analysis
      revealed that the bla (KPC-2) was located on different plasmids. The transfer of
      carbapenem resistance from the three original isolates to Escherichia coli EC600
      was successful by conjugation. An examination of the outer membrane proteins
      showed a lack of a 38-kDa outer membrane protein (OMP) compared with M. morganii
      susceptible to carbapenems. The production of KPC-2 and ESBLs, combined with OMP
      deficiency, resulted in high-level carbapenem resistance in the M. morganii
      strains. The genetic environment around bla (KPC-2) analysis revealed that this
      beta-lactamase was located on the same mobile genetic elements which could
      transfer between different plasmids.

PMID- 21874607
TI  - Ischiofemoral impingement: evaluation with new MRI parameters and assessment of
      their reliability.
AB  - OBJECTIVE: The aim of this study was to describe the magnetic resonance imaging
      (MRI) findings in patients with ischiofemoral impingement (IFI) and to evaluate
      the reliability of these MRI findings. MATERIALS AND METHODS: Seventy hips of 50
      patients with hip pain and quadratus femoris muscle (QFM) edema and 38 hips of 30
      control cases were included in the study. The QFM edema and fatty replacement
      were assessed visually. Ischiofemoral space (IFS), quadratus femoris space (QFS),
      inclination angle (IA), hamstring tendon area (HTA), and total quadratus femoris
      muscle volume (TQFMV) measurements were performed independently by two
      musculoskeletal radiologists. The intra- and interobserver reliabilities were
      obtained for quantitative variables. RESULTS: IFS, QFS, and TQFMV values of the
      patient group were significantly lower than those of controls (P < 0.001). HTA
      and IA measurements of the patient group were also significantly higher than in
      controls (P < 0.05). The QFM fatty replacement grades were significantly higher
      in the patient group than in the control group (P < 0.001). Inter- and intra
      observer reliabilities were strong for all continuous variables. CONCLUSION:
      Clinicians and radiologists should be aware of IFI in patients with hip or groin
      pain, and MRI should be obtained for the presence of the QFM edema/fatty
      replacement, narrowing of the IFS-QFS, and other features that may help in the
      clinical diagnosis of IFI for the proper diagnosis and treatment of the disease.

PMID- 21874608
TI  - Blount disease in a case of Prader-Willi syndrome: why is it not as prevalent as
      in obesity without Prader-Willi syndrome?
AB  - BACKGROUND: Prader-Willi syndrome (PWS) is a genetic disorder causing multisystem
      abnormalities with obesity. Obesity is a well established cause of Blount
      disease. METHODS: A 7-year-old girl with PWS presented with genu varum of the
      left knee with deformity of the proximal medial tibial condyle, which was
      consistent with Blount disease. RESULTS: A lateral physeal stapling and
      subsequent osteotomy for the left proximal tibia and fibula were performed with
      improved anatomical alignment. CONCLUSION: Blount disease has not been reported
      in the literature in association with PWS despite excessive obesity.

PMID- 21874609
TI  - Congenital Spigelian hernia associated with undescended testis.
AB  - BACKGROUND: A Spigelian hernia (SH) is a ventral interstitial hernia through a
      defect in the Spigelian fascia; an undescended testis is sometimes associated
      with this clinical entity in male newborns. The etiopathogenesis, surgical
      anatomy, diagnostic methods, and treatment for this rare condition are discussed
      with a review of the literature. METHODS: A 20-day-old newborn was admitted to
      our hospital for a swelling in the right lower abdomen and undescended testis.
      Physical examination of the abdomen and scrotum revealed a congenital SH
      associated with cryptorchidism. RESULTS: Herniotomy, herniorrhaphy, and
      orchidopexy were performed. In the post-operative period, scrotal abscess
      occurred and was drained. After drainage, the fixed testis was found to be
      atrophic. CONCLUSIONS: This association may be a distinct clinical syndrome. The
      operation time in cases of neonatal SH with undescended testis should be well
      planned because of probable surgical complications such as vascular damage,
      tension, or compression.

PMID- 21874610
TI  - Sweet's syndrome in a neonate with non-B54 types of human leukocyte antigen.
AB  - BACKGROUND: Sweet's syndrome (acute febrile neutrophilic dermatosis) is
      characterized by fever, polymorphonuclear leukocytosis of blood, painful plaques
      on the limbs, face and neck, and histologically a dense dermal infiltration with
      mature neutrophils. Sweet's syndrome is often a complication of hematologic
      malignant disease or drug-induced sensitivity reactions and has a significant
      susceptibility correlated with certain human leukocyte antigen (HLA). METHODS: A
      5-week-old Japanese girl with Sweet's syndrome confirmed by skin biopsy was
      successfully treated and HLA analysis was performed. RESULTS: The patient was one
      of the youngest patients reported with Sweet's syndrome, suggesting the
      importance of the genetic background. Although the HLA types of the patient did
      not have B54, which was reported as a significant susceptibility correlation,
      structural analysis of the patient's HLAs suggested a similar possible motif for
      the bound peptides. CONCLUSION: Studies on the HLA bound peptides and HLA
      structural analysis for patients with Sweet's syndrome would be valuable for
      understanding the molecular mechanism of the pathogenesis.

PMID- 21874611
TI  - Transplacental digoxin therapy for fetal atrial flutter with hydrops fetalis.
AB  - BACKGROUND: Without timely treatment, fetal atrial flutter (AF) could result in
      congestive heart failure, hydrops fetalis and even fetal demise. METHODS:
      Prenatal echocardiography was used to confirm AF and assess fetal cardiac
      function with cardiovascular profile score. Transplacental digoxin therapy was
      adopted, and the patient was followed up for 10 months. RESULTS: The healthy male
      baby was delivered with normal postnatal electrocardiogram and echocardiogram.
      Neither arrhythmia nor neurodevelopmental impairment was found during the follow
      up. CONCLUSION: Timely transplacental digoxin therapy can successfully treat
      fetal AF and allow the fetus to recover from AF associated fetal heart failure
      and hydrops fetalis prior to delivery.

PMID- 21874612
TI  - Colonic adenocarcinoma as a secondary malignancy after treatment of embryonal
      rhabdomyosarcoma.
AB  - BACKGROUND: Survivors of childhood malignancies are known to be at an increased
      risk for developing a variety of secondary cancers. Primary adenocarcinoma of the
      colon is very rare in children and adenocarcinoma of the colon occurring as a
      secondary malignancy in children is much rarer. METHODS: A boy with a history of
      successfully treated embryonal rhabdomyosarcoma developed adenocarcinoma of the
      colon as a secondary cancer. RESULTS: The boy presented with a solid mass of the
      left cheek at 3 years of age. The mass was excised and histological examination
      showed embryonal rhabdomyosarcoma. He was treated with multi-agent chemotherapy
      and local radiotherapy, which resulted in complete remission. Four years later,
      he presented with recurrent colicky abdominal pain and bleeding per rectum and
      was found to have intussusceptions. Colonoscopy revealed a tumor in the
      transverse colon, which was biopsied and proved to be an adenocarcinoma. The boy
      underwent excision followed by chemotherapy using an adult colon cancer regimen.
      He is currently off chemotherapy for 2 years with no evidence of the disease.
      CONCLUSIONS: We report a rare case of colon cancer after treatment of
      rhabdomyosarcoma. Colorectal adenocarcinoma must be kept in mind as a secondary
      neoplasm following treatment for early childhood malignancies although it is
      extremely rare.

PMID- 21874613
TI  - Evaluation of adhesion molecules CD64, CD11b and CD62L in neutrophils and
      monocytes of peripheral blood for early diagnosis of neonatal infection.
AB  - BACKGROUND: This study was undertaken to assess the value of neutrophils CD11b,
      CD64, and CD62L for the early diagnosis of neonatal infection. METHODS: Eighty
      four neonates who were followed up for a suspected neonatal infection were
      included in this study. They were assigned into an infection group (n=49) and a
      non-infection group (n=35). Healthy neonates served as controls (n=35). A full
      sepsis screening was performed and neutrophil and monocyte expressions of CD11b,
      CD64 and CD62L were determined by flow cytometry. RESULTS: The expressions of
      CD64 and CD11b were significantly enhanced in the infection group compared to the
      non-infective group and the controls. CONCLUSIONS: CD64 expression on neutrophils
      and monocytes is a useful diagnostic marker for the early diagnosis of neonatal
      infection. Combination of CD64, CD11b and C reactive protein further enhances the
      sensitivity of the expression and its negative predictive value.

PMID- 21874614
TI  - Acute kidney injury in a girl with ulcerative colitis and cytomegalovirus-induced
      focal segmental glomerular sclerosis.
AB  - BACKGROUND: Mesalamine or 5-aminosalicylic acid (5-ASA) has proven efficacy in
      treating patients with ulcerative colitis (UC). Although mesalamine is considered
      safe, it has been associated with acute interstitial nephritis and renal failure.
      METHODS: Herein we present a case of a child with UC who developed acute renal
      failure on mesalamine therapy. RESULTS: A 15-year-old African-American girl with
      well-controlled UC presented to the Johns Hopkins Hospital with a four-day
      history of high fever, malaise, generalized body aches, and productive non-bloody
      cough. Over the next three days, she developed acute renal failure with fluid
      retention, and elevated serum creatinine and blood urea nitrogen. A kidney biopsy
      showed drug induced acute interstitial nephritis and focal segmental
      glomerulosclerosis with viral inclusion bodies likely secondary to
      cytomegalovirus. CONCLUSION: When treating UC patients with a history of
      underlying renal disease, it is advised to carefully monitor renal function while
      on mesalamine therapy.

PMID- 21874615
TI  - The first reported HLCS gene mutation causing holocarboxylase synthetase
      deficiency in a Vietnamese patient.
AB  - BACKGROUND: Holocarboxylase synthetase deficiency is an inborn error of biotin
      metabolism leading to multiple carboxylase deficiency which is often biotin
      responsive. This disease is believed to be relatively common among the Asian
      population. METHODS: A 6-year-old Vietnamese boy presented with recurrent
      episodes of severe metabolic acidosis precipitated by intercurrent illnesses. An
      extensive skin rash was present since the onset of his illness. Multiple
      carboxylase deficiency was considered a likely diagnosis based on the history and
      the characteristic skin rash. RESULTS: This diagnosis was later confirmed by
      urine organic acid and molecular genetic studies. Urine organic acid showed
      characteristic excretion of glycine conjugates. Serum biotinidase activity was
      normal. Sequencing of the holocarboxylase synthetase gene revealed the patient
      being homozygous for a common mutation R508W. The patient showed a dramatic
      response to biotin within days of its administration. CONCLUSION: This case
      illustrates a potential highly treatable inborn error of metabolism that can be
      recognized on clinical grounds and its favorable response to biotin treatment.

PMID- 21874616
TI  - Acute cerebellitis associated with rotavirus infection.
AB  - BACKGROUND: Rotavirus infection is occasionally associated with central nervous
      system involvement, including cerebellitis. However, the precise clinical
      sequelae of central nervous system disorders and the usefulness of
      neuroradiological examination for clinical therapies, such as steroid pulse
      therapy, have not been clarified. METHODS: We present a case of rotavirus
      cerebellitis examined by magnetic resonance imaging (MRI), magnetic resonance
      spectroscopy, and single photon emission computed tomography. RESULTS: MRI
      demonstrated abnormal intensities in the right cerebellum on fluid attenuated
      inversion recovery images and, much more obviously, on diffusion-weighted images,
      but not on T1- or T2-weighted images. Single photon emission computed tomography
      showed only mild hypoperfusion in the right cerebellum on the 15th day, while 4
      weeks later the image showed remarkably low perfusion in the right cerebellum.
      CONCLUSION: The findings of the reported case suggest the importance of
      performing radiological examinations at early phases of the disease, especially
      by new modalities such as diffusion weighted imaging, to make timely and
      appropriate therapeutic decisions.

PMID- 21874617
TI  - Necrotizing fasciitis of the perineum.
AB  - BACKGROUND: Necrotizing fasciitis is a severe soft tissue infection characterized
      by rapidly progressing necrosis, involving subcutaneous tissues. This rare
      condition carries a high mortality rate and requires prompt diagnosis and urgent
      treatment with radical debridement and antibiotics; but early diagnosis, which is
      essential to successful treatment, remains a challenge. METHODS: Physical
      examination findings, preoperative and operative findings, histopathological
      results of the structure, and follow-up results of the patient are discussed with
      related reports. RESULTS: A 15-month old girl had a history of trivial perineal
      dermatitis after treatment of anemia and pneumonia. Perineal dermatitis
      progressed fastly as necrotizing fasciitis which was successfully managed with
      intensive medical treatment, surgical debridement and reconstructive surgery.
      CONCLUSIONS: Lack of cutaneous findings early in the disease makes the diagnosis
      challenging, so a high suspicion is essential. Recovery of the patient from this
      life-threatening condition needs a multi-disciplinary approach involving
      pediatrics, pediatric surgery, and plastic and reconstructive surgery.

PMID- 21874618
TI  - Maternal obesity associated with inflammation in their children.
AB  - BACKGROUND: This study explored the association between maternal obesity during
      pregnancy and the inflammatory markers, tumor necrosis factor-alpha, interleukin
      6 and high sensitivity C-reactive protein (hs-CRP), and the cytokine,
      adiponectin, in the offspring. METHODS: Weight, height, Tanner stage and
      biomarkers were measured in thirty-four 12-year-old children, from the Infant
      Growth Study, who were divided into high risk (HR) and low risk (LR) groups based
      on maternal pre-pregnancy body mass index (BMI). RESULTS: The two groups differed
      markedly in their hs-CRP levels, but no group difference was found for the other
      three biomarkers. The odds ratio (OR) of HR children having detectable hs-CRP
      levels was 16 times greater than that of LR children after adjusting for
      confounding variables, including BMI z-score, Tanner stages and gender (OR: 16;
      95% CI: 2-123). CONCLUSIONS: These results suggest that maternal obesity during
      pregnancy is associated with later development of elevated hs-CRP in the
      offspring, even after controlling for weight.

PMID- 21874619
TI  - Persistence of antibody to hepatitis B surface antigen among vaccinated children
      in a low hepatitis B virus endemic area.
AB  - BACKGROUND: A potential problem of hepatitis B immunization is that vaccine
      induced antibody to hepatitis B surface antigen (anti-HBs) declines to low levels
      with age. This study investigated the persistence of anti-HBs in vaccinated
      children in a low hepatitis B virus (HBV) endemic area. METHODS: Plasma samples
      of 938 children between ages of 8 months and 15 years were tested for the
      presence of anti-HBs. RESULTS: The seroprotection rate was 60%. Protective
      antibody level was detected in 65% of children one year after vaccination, and in
      30%, 29% and 24% 5, 10 and 15 years after vaccination, respectively. The mean
      anti-HBs titer declined with post-vaccination time (to 66 mIU/mL in 1 year, 60
      mIU/mL in 5 years, 40 mIU/mL in 10 years to 37 mIU/mL in 15 years after
      vaccination). CONCLUSIONS: Children vaccinated against HBV during infancy may
      show low levels of antibody during adolescence. Our data suggest that a booster
      dose of vaccine may be required in low HBV endemic areas.

PMID- 21874620
TI  - Thoracoscopic resection of congenital pulmonary malformations in infants: is the
      feasibility related to the size of the lesion?
AB  - BACKGROUND: The size of congenital pulmonary malformation (CPM) in infants might
      interfere with the feasibility of thoracoscopic resection. This study was
      undertaken to evaluate the impact of the size of CPM on the applicability of
      video-assisted thoracic surgery (VATS) in infants. METHODS: Twenty-two infants
      were operated on for CPM from November 2000 to June 2009. The intra- and
      postoperative course was analyzed retrospectively from patient charts.
      Preoperative scans were evaluated blindly by a radiologist to calculate the
      relation between the maximum size of the lesion and the thoracic diameter in VATS
      and open procedures. RESULTS: VATS was performed in 14 (64%) of the 22 patients
      and thoracotomy in 8. VATS was successfully performed in 11 (79%) of the 14
      patients, whereas VATS was converted to thoracotomy due to lack of overview in 3
      (21%). The mean relative size of CPM at preoperative imaging was 0.34 +/- 0.05
      (range: 0.3-0.4) in patients who received successful VATS, 0.57 +/- 0.06 (range:
      0.5-0.6) in converted cases, and 0.68 +/- 0.10 (range: 0.5-0.8) in infants who
      underwent thoracotomy. The relative CPM size was significantly lower in
      successful VATS than in cases of conversion (P<0.01) and thoracotomy (P<0.01).
      CONCLUSIONS: The relative size of CPM at preoperative imaging might be useful
      information for a decision-making on the use of VATS in infants. A relative CPM
      size below 0.5, which is less than half of the thoracic diameter, indicates a
      good feasibility for thoracoscopic resection of CPM. A larger size may indicate
      that VATS might be technically difficult.

PMID- 21874621
TI  - Adrenal hemorrhage in newborns: a retrospective study.
AB  - BACKGROUND: Adrenal hemorrhage (AH) is a relatively uncommon condition in
      neonates. This study aimed to review the clinical, laboratory and
      ultrasonographic findings of AH in newborns. METHODS: The medical records of 13
      newborns with AH who had been admitted to our neonatal intensive care unit were
      retrospectively reviewed. RESULTS: Of the 13 newborns with AH, 8 (62%) were term
      and 10 (77%) were male babies. Clinical presentations included neonatal jaundice
      (85%), paleness and/or flank mass (38%), discoloration of the scrotum (15%), and
      hypotonia/lethargy or hypotension (8%). Five newborns had anemia and four had
      adrenal insufficiency. Adrenal insufficiency was observed in 80% of the premature
      infants with AH. AH occurred on the right side in 9 patients (69%). The most
      predisposing cause of AH was disseminated intravascular coagulation secondary to
      sepsis or perinatal hypoxia in preterm infants, and large for gestational age in
      term infants. Ultrasonography (USG) revealed a hypoechoic mass in 7 newborns
      (54%), a mixed solid-liquid mass in 5 (38%), and an echogenic mass (8%) in 1.
      Hemorrhage disappeared within 8.6 +/- 4.5 (4-16) weeks. CONCLUSIONS: AH occurs in
      the newborns with unexplained jaundice. Adrenal insufficiency is more frequent in
      preterm than in mature infants. Abdominal USG is required to determine AH in a
      newborn with swelling and bluish discoloration of the scrotum. Serial USG is the
      best modality for monitoring AH to prevent unnecessary surgery.

PMID- 21874622
TI  - A rapid one-step immunochromatographic assay for the detection of asiaticoside.
AB  - Asiaticoside has been identified as the most active compound in Centella
      asiatica. In order to screen a large number of plant samples for the presence of
      asiaticoside, a rapid and simple technique is required that utilizes small
      quantities for test samples. In this study, an immunochromatographic strip test
      has been developed for the detection of asiaticoside in plant samples that uses a
      monoclonal antibody against asiaticoside. The limit of detection for the strip
      test was 12.5 MUg/ml. Immunoassay using monoclonal antibodies could be useful for
      the determination of small quantities of asiaticoside in plant extracts.

PMID- 21874623
TI  - Improving successful rate of transcranial electrical motor-evoked potentials
      monitoring during spinal surgery in young children.
AB  - INTRODUCTION: This prospective study was to investigate the successful rate of
      intraoperative motor evoked potentials (MEP) monitoring for children (<12 years
      old) with congenital scoliosis. MATERIALS AND METHODS: A consecutive series of 27
      young children (7 girls and 20 boys; from 1 to 11 years old) between September
      2007 and November 2009, were enrolled to this study. 12 patients received general
      anesthesia based on TIVA, induced with propofol 2-4 mg/kg and fentanyl 3-5 ug/kg
      followed by a continuous infusion of propofol (20-150 ug/kg/min, at mean of 71.7
      ug/kg/min). The other 15 patients received combined inhalation and intravenous
      anesthesia, induced with sevoflurane and fentanyl 3-5 ug/kg and maintained by
      sevoflurane (0.5-1%). The maintenance of anaesthesia management was performed
      with stable physiological parameters during surgery. RESULTS: Intraoperative MEP
      monitoring was successfully performed in all patients, while SEP was successfully
      performed in 26 of 27 patients. There was no significant difference of successful
      rates between SEP and MEP monitoring (P > 0.05). As well, no difference in MEP
      successful rates was observed in two groups with different anesthetic techniques.
      No wake-up test and no post-operative neurological deficits occurred in this
      series of patients. CONCLUSION: Low dose anesthesia by either TIVA with propofol
      or sevoflurane-based mixture anesthesia protocol can help the intraoperative
      spinal cord monitoring to successfully elicit MEP and perform reliable monitoring
      for patients below 12 years of age.

PMID- 21874624
TI  - Effect of direct vertebral body derotation on the sagittal profile in adolescent
      idiopathic scoliosis.
AB  - PURPOSE: We sought to clarify the effect of applying derotation maneuvers in the
      correction of adolescent idiopathic scoliosis (AIS) on the sagittal plane.
      METHODS: We retrospectively queried a large, multicenter, prospectively collected
      database for patients who underwent surgical correction of AIS. All patients had
      at least 2 years of follow-up and documentation as to whether or not a derotation
      maneuver was performed during surgery. All patients underwent posterior spinal
      fusion with pedicle screw constructs. Patients who underwent concurrent anterior
      procedures were excluded. RESULTS: A total of 323 patients were identified, of
      whom 66 did not have direct vertebral body derotation (DVBD) maneuvers applied
      during the deformity correction. The remaining 257 had a vertebral body
      derotation maneuver performed during their surgical correction. Although no
      significant differences were identified between the two groups when comparing pre
      op and post-op thoracic kyphosis using T2-12 and T5-12 endplates, the absolute
      change in angulation measured from T2-12 was significantly different between the
      two groups. Postoperatively, the derotation group had a mean decrease in thoracic
      kyphosis of 5.1+/-15.3 degrees  as compared to 10.8+/-18.9 degrees  in the
      control group, P = 0.03. CONCLUSION: Although patients in both groups had
      decreased mean thoracic kyphosis postoperatively, application of DVBD in the
      correction of scoliosis did not additionally worsen the sagittal profile.

PMID- 21874625
TI  - Pedicle screw instrumentation in adolescent idiopathic scoliosis (AIS).
AB  - INTRODUCTION: Pedicle screw instrumentation in AIS has advantages of rigid
      fixation, improved deformity correction and a shorter fusion, but needs an
      exacting technique. MATERIALS AND METHODS: The author has been using the K-wire
      method with intraoperative single PA and lateral radiographs, because it is safe,
      accurate and fast. Pedicle screws are inserted in every segment on the correction
      side (thoracic concave) and every 2-3 on the supportive side (thoracic convex).
      After an over-bent rod is inserted on the corrective side, the rod is rotated 90
      degrees  counterclockwise. This maneuver corrects the coronal and sagittal
      curves. Then the vertebra is derotated by direct vertebral rotation (DVR)
      correcting the rotational deformity. The direction of DVR should be opposite to
      that of the vertebral rotation. A rigid rod has to be used to prevent the rod
      from straightening out during the rod derotation and DVR. The ideal
      classification of AIS should address all curve patterns, predicts accurate fusion
      extent and have good inter/intraobserver reliability. The Suk classification
      matches the ideal classification is simple and memorable, and has only four
      structural curve patterns; single thoracic, double thoracic, double major and
      thoracolumbar/lumbar. Each curve has two types, A and B. When using pedicle
      screws in thoracic AIS, curves are usually fused from upper neutral to lower
      neutral vertebra. Identification of the end vertebra and the neutral vertebra is
      important in deciding the fusion levels and the direction of DVR. In lumbar AIS,
      fusion is performed from upper neutral vertebra to L3 or L4 depending on its
      curve types. CONCLUSIONS: Rod derotation and DVR using pedicle screw
      instrumentation give true three dimensional deformity correction in the treatment
      of AIS. Suk classification with these methods predicts exact fusion extent and is
      easy to understand and remember.

PMID- 21874626
TI  - The growing spine: how spinal deformities influence normal spine and thoracic
      cage growth.
AB  - PURPOSE: This article aims to provide an overview of how spinal deformities can
      alter normal spine and thoracic cage growth. METHODS: Some of the data presented
      in this article are gathered from studies performed in 1980 and 1990, and their
      applicability to populations of different ethnicity, geography or developmental
      stage has not yet been elucidated. In the present article, older concepts have
      been integrated with newer scientific data available to give the reader the basis
      for a better understanding of both normal and abnormal spine and thoracic cage
      growth. RESULTS: A thorough analysis of different parameters, such as weight,
      standing and sitting height, body mass index, thoracic perimeter, arm span, T1-S1
      spinal segment length, and respiratory function, help the surgeon to choose the
      best treatment modality. Respiratory problems can develop after a precocious
      vertebral arthrodesis or as a consequence of pre-existing severe vertebral
      deformities and can vary in patterns and timing, according to the existing degree
      of deformity. The varying extent of an experimental arthrodesis also affects
      differently both growth and thoracopulmonary function. CONCLUSIONS: Growth is a
      succession of acceleration and deceleration phases and a perfect knowledge of
      normal growth parameters is mandatory to understand the pathologic modifications
      induced on a growing spine by an early onset spinal deformity. The challenges
      associated with the growing spine for the surgeon include preservation of the
      thoracic spine, thoracic cage, and lung growth without reducing spinal motion.

PMID- 21874627
TI  - A large-sized bubbling appearance of the glomerular basement membrane in a
      patient with pulmonary limited AL amyloidosis and a past history of lupus
      nephritis.
AB  - We report an unusual pathological finding, a large-sized bubbling appearance of
      the glomerular basement membrane (GBM), in a patient with pulmonary limited AL
      amyloidosis and a past history of lupus nephritis. The first renal biopsy
      specimen from 10 years ago, when systemic lupus erythematosus was diagnosed,
      demonstrated mild mesangial proliferation and subepithelial deposits (WHO
      classification: III + V). Light microscopy of the current biopsy using periodic
      acid methenamine silver (PAMS) stain demonstrated a large-sized bubbling
      appearance of the GBM; however, very weak immunoglobulin and complement
      deposition was observed in immunofluorescence studies. Routine electron
      microscopy demonstrated partial subendothelial expansion with electron-lucent
      materials, but no electron-dense deposits or amyloid fibrils. Electron microscopy
      with PAMS stain revealed electron-lucent endothelial scalloping, including some
      cellular components and microspheres in the GBM; however, it is not clear if
      these materials are derived from endothelial cells. One possibility is that these
      unique findings represent a recovery phase of lupus membranous nephritis; another
      is that these findings correspond to a new disease entity.

PMID- 21874629
TI  - [Panretinal laser photocoagulation with reduced pulse duration--first experience
      with linear multispot cascades].
AB  - BACKGROUND: VISULAS 532 s VITE is a 532 nm laser device which allows semi
      automated photocoagulation in fast cascades with short pulse durations in
      addition to conventional retinal single-spot coagulation. METHODS: In a
      prospective randomised study 101 peripheral laser treatments for retinopathy of
      various origins were divided into two groups: control group A (n = 35)
      coagulation in conventional single-spot modus and study group B (n = 66)
      coagulation with the new semiautomated VITE-function of VISULAS 532 s. Spot
      diameter was the same in both groups (300 um at the retina). Patients were asked
      about pain immediately after therapy on a scale ranging from 0 ( = no pain) up to
      10 ( = maximum pain). From video recording, treatment times were measured. After
      each treatment, a photo-documentation followed to control the laser effects. The
      shorter laser pulses in group B were offset by higher laser power to achieve
      similar moderate effects. RESULTS: In group A 509 (462-609) effects were set with
      a pulse duration of 100-150 ms and power of 157 (70-380) mW. 46.0% of the
      patients complained of pain at an intensity of 4.4 (2-8). The treatment time was
      73.4 (61.6 to 103.7) s per 100 effects. In group B 555 (120-600) effects were set
      with pulse duration of 20 ms and a power of 286 (120-600) mW. 1.3% of the
      patients complained of pain at an intensity of 3 and 4. The treatment time was
      49.4 (24.0-97.5) s per 100 effects. None of the groups experienced complications.
      CONCLUSION: The semiautomated function of the laser using a 20 ms pulse duration
      allows almost painless coagulation of the retina. The treatment times can be
      reduced by one third. This leads to improved patient compliance. Long-term
      results regarding the regression of proliferative changes are still lacking.

PMID- 21874628
TI  - Responses to environmental stresses in woody plants: key to survive and
      longevity.
AB  - Environmental stresses have adverse effects on plant growth and productivity, and
      are predicted to become more severe and widespread in decades to come.
      Especially, prolonged and repeated severe stresses affecting growth and
      development would bring down long-lasting effects in woody plants as a result of
      its long-term growth period. To counteract these effects, trees have evolved
      specific mechanisms for acclimation and tolerance to environmental stresses.
      Plant growth and development are regulated by the integration of many
      environmental and endogenous signals including plant hormones. Acclimation of
      land plants to environmental stresses is controlled by molecular cascades, also
      involving cross-talk with other stresses and plant hormone signaling mechanisms.
      This review focuses on recent studies on molecular mechanisms of abiotic stress
      responses in woody plants, functions of plant hormones in wood formation, and the
      interconnection of cell wall biosynthesis and the mechanisms shown above.
      Understanding of these mechanisms in depth should shed light on the factors for
      improvement of woody plants to overcome severe environmental stress conditions.

PMID- 21874630
TI  - [Photocoagulation of age-related juxtapapillary choroidal neovascularisation].
AB  - BACKGROUND: The aim of this study was to evaluate retrospectively the clinical
      outcome of retinal photocoagulation of age-related juxtapapillary choroidal
      neovascularisation (CNV) with macular oedema. Juxtapapillary CNV represents a
      rare form of extrafoveal CNV in age-related macular degeneration (AMD). PATIENTS
      AND METHODS: In 15 eyes of 14 patients with age-related juxtapapillary choroidal
      neovascularisation, CNV was treated with several rows of frequency doubled Nd:YAG
      laser (532 nm) irradiation to protect the fovea. Classification of the CNV was
      performed with fluorescein angiography. Best corrected visual acuity was
      determined before and after photocoagulation. Follow-up time was 1 - 32 months.
      RESULTS: In 13 eyes the juxtapapillary CNV was occult (87 %), one eye had a
      classic, one eye a minimally classic form. In 13 eyes (87 %) the centre of the
      fovea showed macular oedema in spite of the extrafoveal location of the CNV. Of
      these 13 eyes, in 10 eyes (77 %) visual acuity increased after photocoagulation.
      7 eyes (53 %) had an increase in visual acuity of 1 or 2 lines, 3 eyes of >= 4
      lines. 2 eyes showed a stable visual acuity, in 1 eye visual acuity deteriorated
      after photocoagulation. In 2 eyes without foveal involvement of macular oedema,
      CNV was located in the papillo-macular bundle and threatened the centre of the
      fovea. Postoperative visual acuity in theses eyes was stable after 1 and 5
      months. CONCLUSION: The therapeutic benefit of photocoagulation of juxta- and
      extrafoveal classic CNV has already been proven. According to our results,
      photocoagulation is an effective therapeutic approach in the treatment of age
      related juxtapapillary CNV especially, in the occult form, when the fovea is
      threatened by or involved in the macular oedema.

PMID- 21874631
TI  - The EFSUMB Guidelines and Recommendations on the Clinical Practice of Contrast
      Enhanced Ultrasound (CEUS): update 2011 on non-hepatic applications.

PMID- 21874633
TI  - [Clinical and economic challenges of moderate preterm babies born between 32+0
      and 36+6 weeks of gestation].
AB  - BACKGROUND: Preterm births show a worldwide increasing incidence. The majority of
      preterm births occur between 32+0 and 36+6 weeks of gestation and are associated
      with an increased rate of maternal and neonatal morbidity. The focus of our
      research is the clinical and economical analysis of all preterm births between
      32+0 and 36+6 weeks of gestation in a German level 1 perinatal centre over a
      period of 3 years. MATERIALS AND METHODS: A retrospective analysis of all preterm
      births between 32+0 and 36+6 weeks of gestation in the University Hospital Mainz
      from 2007 to 2009 was undertaken. Data were collected using our electronic
      documentation system. Gestational age at delivery, mode of birth, indication for
      delivery, duration of the peripartum treatment, treatment of the newborn in the
      children's hospital, birth weight and therapy costs were evaluated. RESULTS: We
      recorded 407 moderate preterm births in total; this amounts to a rate of of 10%
      of all births. Major causes of prematurity were PPROM, preterm labour and
      preeclampsia/HELLP. Maternal and fetal systemic diseases were more uncommon.
      Rates of Caesarean sections (62%) and of neonatal inpatient treatment needs
      (58.5%) were high. Maternal treatment costs were 332 Euro/day. The mean duration
      of maternal inpatient treatment was 13.15 days. DISCUSSION: Moderate preterm
      birth is associated with maternal morbidity frequently due to a high rate of
      Caesarean sections. Neonatal morbidity is also increased. In comparison with
      previous research, we saw an increased rate of pregnancy complications. This
      could be typical for a level 1 perinatal centre. Moderate preterm birth is seen
      as the cause of considerable treatment costs.

PMID- 21874634
TI  - Metopism: as an indicator of cranial pathology; a good example from Iranian
      plateau.
AB  - Metopism had been observed as a genetic trait. Recent studies have brought to
      light that it can get as an indicator of cranial pathology. An example of this
      pathology has been studied by this author on an Iranian skeletal sample. The
      purpose of this paper is to provide basic information on the subject and thereby
      to create awareness among Iranian anthropologists and archaeologists of this new
      line of evidence as well as to pathologists.

PMID- 21874635
TI  - Evaluation of effects of Zingiber officinale on salivation in rats.
AB  - There are some herbal plants in Iranian traditional system of medicine which are
      believed to be excellent remedies to alleviate the symptoms of xerostomia. The
      aim of the present study was to evaluate the effect of systemic administration of
      seven different herbal extracts on the rate of salivation in rats. The extracts
      of 7 herbs; Zingiber officinale Roscoe (Zingiberaceae), Citrus sinensis (L.)
      Osbeck (Rutaceae), Artemisia absinthium L. (Asteraceae), Cichorium intybus L.
      (Asteraceae), Pimpinella anisum L.(Apiaceae), Portulaca oleracea
      L.(Portulacaceae), Tribulus terrestris L. (Zygophyllaceae) were prepared. Nine
      groups of animals (including negative and positive control groups) were used and
      seven rats were tested in each group. After the injection of extracts, saliva
      volume was measured gravimetrically in four continuous seven-minute intervals.
      The results showed that after injection of ginger extracts salivation was
      significantly higher as compared to the negative control group and other herbal
      extracts in all of the four intervals (P<0.01). The peak action of the ginger was
      during the first 7-minute interval and following this, salivation decreased to
      some extent. The present study suggests that the extract of Zingiber offiicianle
      can increase the rate of salivation significantly in animal model. Further
      investigations on different constituents of ginger seem to be essential to
      identify the responsible constituent for stimulation of saliva secretion.

PMID- 21874637
TI  - Laparoscopic versus open appendectomy; which method to choose? A prospective
      randomized comparison.
AB  - Appendicitis is the most common surgical emergency with the incidence rate of 6
      10%. Although several studies have compared the two approaches of open (OA) and
      laparoscopic appendectomy (LA) the technique of choice is still a matter of
      controversy. Considering this background we designed a study to compare OA and LA
      outcomes in our center. One hundred patients were included in this study
      performed from April 2008 to April 2009 at Shahid Sadoughi hospital, Yazd, Iran.
      Patients who gave informed consent were randomized to either OA or LA groups and
      were operated by McBurney's or laparoscopic technique, respectively. Patients
      received our center's routine diet, antibiotics and analgesic regimens. The
      patients' pain was measured by visual analogue scale (VAS) at their entrance to
      the recovery room and in 6-hour intervals up to 24 hours. Post-operation follow
      up visits were in weeks 1, 2 and 4. The data of operation time, hospital stay,
      intra-operation complications, time to resume normal activity, short term
      complications and neuralgia were collected and analysed. The average operation
      time was 34.4+/-8.42 min in LA and 41.7+/-8.84 in OA hand (P=0001). No intra
      operative complication and no LA to OA conversion were encountered in operations.
      Post-operative complication rate was higher in OA group (n=10) compared to LA
      (n=3). The post-operative pain showed less pain in OA only at 6 and 12 hours post
      operative times. Patients' mean hospital stay was 52.32+/-19.2 and 42.96+/-13.8
      hours in LA and OA groups, respectively (P=0.003). Time to resume normal activity
      didn't show a significant difference between two groups (P=0.53). Only one case
      of neuralgia in the OA group was confronted in the follow up visits. LA has less
      complications and cosmetic scar with the cost of more pain. Decision between OA
      and LA for each patient should be made individually.

PMID- 21874636
TI  - Investigation of the assembly of chylomicrons in hamster enterocytes using
      pluronic-L81 acid as a probe.
AB  - A major function of the enterocytes is absorption, processing, and export of
      dietary lipids into the lymphatic system. Pluronic L-81 is a non-ionic
      hydrophobic surfactant, which specifically inhibits lipid absorption in the
      intestine when administered in vivo. This compound is therefore an attractive
      probe to perturb and investigate the molecular and intracellular events in
      chylomicron assembly in the enterocytes. In the present study pluronic acid was
      administered to hamsters followed by isolation of the enterocytes and cell
      fractionation to investigate the effect of pluronic acid on intracellular events
      in lipid absorption. Four types of diet were administered to hamsters for three
      weeks; low-fat chow, high-fat chow and each diet with or without added pluronic
      acid. Sub-cellular fractions of freshly isolated enterocytes were prepared.
      Consistent with morphological observation, the high fat diet resulted in a three
      fold increase in the triacylglycerol (TAG) content of the enterocytes and
      addition of pluronic acid to either the low fat or the high fat diets resulted in
      a ten-fold increase in cellular TAG levels. Determination of the mass of TAG and
      the time course of incorporation of 3H-triolein, administered by gavage, showed
      that the increased TAG was recovered in the microsomal (endoplasmic reticulum)
      fraction and the cytosol. In microsomes, increased TAG was recovered mainly in
      the membrane although there was a significant amount in the microsomal luminal
      contents. Pluronic acid therefore acts at the level of the endoplasmic reticulum
      and inhibits the assembly of apo-B48 with chylomicron TAG. The excess TAG is
      transferred to cytosolic stores.

PMID- 21874638
TI  - The prevalence of distal junctional kyphosis following posterior instrumentation
      and arthrodesis for adolescent idiopathic scoliosis.
AB  - Distal junctional kyphosis (DJK) is a radiographic finding in patients that
      undergo spinal instrumentation and fusion, since there is an abrupt transition
      between fixed and mobile spinal segments.The true incidence of DJK is variable in
      literature and seems that has a multifactorial etiology. A consecutive series of
      130 patients (mean age 15.6 years) with adolescent idiopathic scoliosis who
      underwent posterior spinal fusion and instrumentation were evaluated by analyzing
      coronal and sagittal angulation and balance measurements from standing
      radiographs obtained pre-operatively, within 6 weeks post-operation, at two years
      postoperative and at the latest follow-up. There was 35 male and 95 female. The
      mean time of follow-up was 36 months. The incidence of DJK at latest follow-up
      was 6.9% (9 patients). In DJK group, distal junctional angle from pre-operative
      of -12.5 degrees  lordosis (-30 to 0) reached to -5.5 degrees  (P=0.015) at 6
      weeks postoperation and to -1.4 degrees  (-20 to 12 degrees ) (P=0.000) at 2
      years follow-up,with mean of 12.1 degrees  kyphotic change (10-20 degrees ). In
      non DJK group, distal junctional angle from pre-operative angle of -7.5 degrees 
      reached -8.1 degrees  at 2 years follow-up (P=0.43). The mean age of DJK group at
      surgery was 17 years and for non-DJK group was 15.4 years (P=0.022). Distal
      junctional kyphosis was less common in this study than previous reports and
      stabilized after two years. The magnitude of coronal cobb angles or multiplicity
      of coronal curves had no effect in developing DJK that may be prevented by
      incorporation of the first lordotic disc into the fusion construct.

PMID- 21874639
TI  - Correlation between anterior mitral leaflet concavity area and ischemic induced
      mitral regurgitation severity by echocardiography.
AB  - Functional mitral regurgitation (MR) results from left ventricular remodeling,
      leaflet tethering or tenting. Coronary artery disease is one of the important
      causes of functional MR due to tethering. Detection of functional MR and its
      severity are important factors in patient prognosis. There are different methods
      for detection of functional MR and its severity, including anterior mitral
      leaflet concavity area (AMLCA). In this cross sectional study 32 patients, 19
      male with three vessel disease (3VD) who were candidate for coronary artery
      bypass grafting (CABG) with or without mitral valve replacement were selected.
      The patients had functional MR in ventriculography. AMLCA was determined by long
      axis view of transthorasic echocardiography (TTE). In this study 32 patients with
      3VD and MR were selected (15 mild, 15 moderate and 2 cases with severe MR). The
      mean age was 62 +/- 12 years. In these patients AMLCA were 0.1- 0.43 cm2 in
      transthorasic echocardiography. The findings of this study showed strong
      association between anterior mitral leaflet concavity area and functional MR
      severity (r=0.89) in parasternal long axis (LAX) view of TTE. According to these
      findings the relation between functional MR and AMLCA was a linear relationship
      and increase in severity of functional MR was in concordance with increasing of
      anterior mitral leaflet concavity area (P=0.001). Mitral leaflet concavity area
      in the parasternal LAX view provides rapid and reliable recognition of functional
      MR due to coronary artery disease and is quantitatively related to the degree of
      such MR. We recommend further study with more subjects and ischemic functional MR
      and AMLCA.

PMID- 21874640
TI  - Pattern of coronary artery disease risk factors in population younger than 55
      years and above 55 years: a population study of 31999 healthy individuals.
AB  - More than eighty percent of patients with coronary heart diseases (CHD) have
      conventional risk factors. Prevalence of well known risk factors seems to show a
      different pattern in younger patients and individual above 55 years. To evaluate
      the pattern of conventional CHD risk factors in healthy individuals in two
      different age groups. A large scale population based survey of 31999 individuals
      from ten medical centers was designed. Screening of risk factors was performed
      upon these protocols: taking medical history, physical examination and blood
      tests of complete blood cell counts, fasting blood sugar, lipid profile,
      urinalysis and creatinine. Prevalence of the risk factors in healthy people aged
      above 55 years were: 8.1% for systolic blood pressure (SBP)>140 mmHg, 3.8% for
      diastolic blood pressure (DBP)>90 mmHg, 13.9% for fasting blood glucose
      (FBS)>=126 Mg/dl, 36.9% for total cholesterol>200 Mg/dl, 19.2% for triglyceride
      (TG)>200 Mg/dl, 67.8% for HDL-c<40 Mg/dl, 27.2% for LDL-c>130 Mg/dl, 4.72 for
      TC/HDL-c ratio, 2.88 for LDL-c/HDL/c ratio and 4.24 for TG/HDL-c ratio.
      Prevalence of risk factors in individuals younger than 55 years were: 1.7% for
      SBP>140 mmHg, 1.2% for DBP>90 mmHg, 5.2% for FBS>=126 Mg/dl, 31.3% for TC>200
      Mg/dl, 21.5% for TG>200 Mg/dl, 69.4% for HDL-c<40 Mg/dl, 23.2% for LDL-c>130
      Mg/dl, 4.7 for TC/HDL-c ratio, 2.83 for LDL-c/HDL-c ratio and 4.43 for TG/HDL-c
      ratio. In univariate model of analysis: prevalence of the risk factors were
      significantly higher in age above 55 years than in people younger than 55 years
      except for hypertriglyceridemia and HDL-c<40 Mg/dl. In a multivariate model of
      logistic regression, pattern of following CHD risk factors remained to
      demonstrate a statistically significance difference between two age groups:
      FBS>=126 Mg/dl P=0.006, TG>200 Mg/dl P= 0.002, HDL-c<40 Mg/dl P= 0.019, education
      status P=0.001, sex P=0.012, and SBP>140 mmHg P=0.001. Pattern of such a CHD risk
      factors of FBS>=126 Mg/dl, TG>200 Mg/dl, HDL-c<40 Mg/dl, education status, sex
      and SBP>140 mmHg demonstrated a statistically significant difference in the age
      above 55 years to the healthy people younger than 55 years. These results cab be
      implicated to set up prediction models for stratifying individuals at higher risk
      of CHD.

PMID- 21874641
TI  - Acute glomerulonephritis: a 7 years follow up of children in center of Iran.
AB  - Acute glomerulonephritis (AGN) is a type of renal disease which indicates the
      inflammation of glomerulus and nephrons. This study was carried on 94 children,
      <15 years old with the diagnosis of AGN who were admitted to Qom and Yazd's
      hospitals between 2000 and 2006. Data were collected using hospital records on
      admission, progression notes and outpatient follow up. Among 94 patients, 55.3%
      were male and 44.6% were female. Mean age of patients was 8.2+/-2.7 years old.
      Acute post streptococcal glomerulonephritis (APSGN) was reported in 92.5%,
      membranoproliferative glomerulonephritis in 4.2%, hemolytic uremic syndrome in
      2.1% and IgA nephropathy in 1.06%. There was no significant differences between
      GN types and gender (P=0.54). Clinical manifestation included edema in 68.8%,
      oliguria in 36.3%, gross hematuria in 69.1%, HTN in 61.7% and anuria in 1.06%.
      Microscopic hematuria was detected in all patients. In the time of follow up none
      of patients had hypertension, 3.1% had proteinuria and 6.3% had microscopic
      hematuria. APSGN is the most common causes of AGN in Qom and Yazd's children.
      Early diagnosis and treatment of APSGN may protect children from long term
      morbidity and mortality and improve quality of life.

PMID- 21874642
TI  - Tetanus immunity in individuals aged 50 years or older in Kashan, Iran.
AB  - Tetanus can be only prevented by vaccination because immunity against this
      disease is rarely acquired, even by natural infections. To maintain long-term
      protective immunity against tetanus, booster immunization is essential for
      adolescents and adults. Most hospitalized cases and virtually all deaths occur in
      people over 60 years of age. The purpose of this study was to investigate the
      degree of protective tetanus immunity among 50 years of age and older people in
      Kashan city, Iran. This cross-sectional study carried out on 180 randomly
      individuals aged 50 years or older who were visiting a central laboratory for
      health examinations in 2008. Participants' serum levels of tetanus antitoxin were
      measured by enzyme linked immunosorbent assay. A standard questionnaire was used
      to collect demographic data and information about risk factors. The prevalence of
      protective tetanus immunity in various age groups was described and
      sociodemographic factors that potentially influenced the degree of tetanus
      immunity were analyzed. Overall, 180 persons were included. Of these, 72 (40%)
      had never received a toxoid booster, while 47 (26.1%) had received a booster at
      least once. Among all participants, 30 (16.7%) had protective tetanus antitoxin
      levels (>= 0.11 IU/mL), and 34 (18.9%) had protective antitoxin levels without
      the need of an immediate booster >=0.51 IU/mL. Among 86 participants aged >60
      years, 6 (7%) had protective antitoxin levels >=0.1-1 IU/mL, and 5(5.8%) had
      protective antitoxin levels >=1 IU/mL. Male gender and prior receipt of toxoid
      booster(s) were associated with protective tetanus immunity. Tetanus antitoxin
      levels declined with age. It appears that most 50 years of age and older adults
      do not have protective levels of tetanus antitoxin because of inadequate
      vaccination coverage. There is a need to improve the immunity levels of this age
      group. It is recommended to vaccinate elderly people against tetanus.

PMID- 21874643
TI  - A survey on substance abuse related deaths referred to Tehran's Legal Medicine
      Organization during 2007 and 2008.
AB  - Doubtlessly one of the major problems in Iran is drug abuse or substance abuse.
      The transmission of HIV/AIDS has made the problem so complicated that has created
      an urgent need for a campaign against this awful phenomenon. The objective of
      this study-that was carried out through the cross-sectional method- is
      considering the situation of the addict death and the related factors. The target
      population consists of the corpses of the addicts referred to the Legal Medicine
      Organization of Tehran during 2007 and 2008. The cadavers were examined in the
      preliminary stage. The blood, urine and the contents of the gall-bladder, stomach
      and viscera were collected and sent to the toxicology laboratory to examine and
      find narcotics metabolites and other drugs. The samples of the brain, heart,
      lungs, liver and kidneys were sent to the pathology laboratories. All of the
      extracted data were recorded and analyzed using SPSS software. It was diagnosed
      that 248 cases (79.7%) out of the total 311 in this study, died of substance
      abuse. Totally 300 cases were reported as male addicts (96.5%). The oldest and
      youngest addicts were 49 and 17 respectively. The most frequent drugs used were
      heroin and combination of heroin and opium. No meaningful difference was observed
      between the death cause of different groups of drug abusers . It seems that the
      increase in the population of the substance users is the main cause of frequency
      changes of the addicts' deaths.

PMID- 21874644
TI  - Linguistic validation of the Irritable Bowel Syndrome-Quality of Life
      Questionnaire for Iranian patients.
AB  - There is a growing interest of clinical and epidemiological researches in the
      field of functional gastrointestinal disorders in our society. Accordingly,
      validated and culturally adapted instruments are required for appropriate
      measurement of variables specially the quality of life. The aim of our study was
      the linguistic validation of the Irritable Bowel Syndrome-Quality of Life
      questionnaire (IBS-QOL) for Iranian IBS patients with Persian language. Following
      the standard forward-backward translation method, the IBS-QOL was translated into
      the Persian language and completed by 141 IBS patients. Patients also completed
      the IBS Symptom Severity Scale (IBS-SSS) and Hospital Anxiety and Depression
      Scale (HADS). One-week retest was performed on 30 randomly selected patients.
      Internal consistency and test-retest reliability were assessed using Cronbach's
      alpha and intraclass correlation coefficient (ICC), respectively. To analyze the
      discriminant validity, the IBS-QOL scores was correlated to the IBS-SSS and HADS
      scores. According to the results, reliability analyses were acceptable for all of
      the IBS-QOL domains (Cronbach's alpha=0.68 to 0.90 and ICCs=0.77 to 0.91).
      Discriminant validity was supported by the presence of correlations of the IBS
      QOL scores with disease severity (r = -0.628), depression (r = -0.692), and
      anxiety (r = -0.711) scores; P < 0.001. These results indicate that the Persian
      version of the IBS-QOL is a reliable instrument with sufficient psychometric
      requirements to assess quality of life in Iranian IBS patients with Persian
      language.

PMID- 21874646
TI  - Wart lesion in a patient associated with HIV infection and treatment under IMOD
      therapy.
AB  - We report a 27-year-old hemophilic male who was HIV positive and under Highly
      Active Antiretroviral Therapy (HAART) along with wart lesions. When IMOD therapy
      started concurrently with HAART, the skin lesions disappeared.

PMID- 21874645
TI  - Conservative management of placenta increta: case report and literature review.
AB  - Placenta increta, a rare complication of pregnancy, is associated with
      significant postpartum hemorrhage often requiring emergency hysterectomy. We
      report a case of conservative management, with a combination of parenteral
      methotrexate, serial ultrasound and beta-hCG assessment. Serum beta-hCG levels
      were undetectable after 8 weeks of therapy. A scan at 6 months showed complete
      involution of the uterus. Review of the literature discussing the diagnostic
      tools, clinical features, management and outcome of pregnancies with placenta
      increta.

PMID- 21874647
TI  - Diffuse myelitis after treatment of cerebral aspergillosis in an immune competent
      patient.
AB  - Presentation of an unusual case of cerebral aspergillosis in an immune competent
      patient who was treated successfully but symptoms and signs of a demyelinating
      process following initial recovery has been occurred. A 29-year-old male with
      focal seizure. Brain MRI revealed small multiple hemispheric and dural lesions.
      An open biopsy was conducted. Histological evaluation revealed hyphe-like
      structure in the necrotic area, within vessel walls, and lumina, suggestive
      aspergillus fumigatus . Furthermore, brancheal hyphae in potassium hydrxide 15%
      and colonies on sabourud dextrose agar were observed. Based of the above findings
      the patient underwent anti fungal therapy. The patient recovered and continued a
      normal life however a follow up MRI was performed after 3 months from recovery.
      No significant abnormality was observed from the MRI procedure. One month later
      the patient developed signs and symptoms of spinal cord involvement which seemed
      to be the result of myelitis. A brain MR showed no abnormalities .Therefore it
      seemed reasonable to administer corticosteroid as a treatment for suspected
      active demyelinating process. During the above treatment, signs and symptoms of
      myelopathy disappeared and a whole spine MRI showed remarkable improvement.

PMID- 21874648
TI  - CD44 is critical for airway accumulation of antigen-specific Th2, but not Th1,
      cells induced by antigen challenge in mice.
AB  - CD44 is a cell adhesion molecule involved in lymphocyte infiltration of inflamed
      tissues. We previously demonstrated that CD44 plays an important role in the
      development of airway inflammation in a murine model of allergic asthma. In this
      study, we investigated the role of CD44 expressed on CD4(+)  T cells in the
      accumulation of T-helper type 2 (Th2) cells in the airway using CD44-deficient
      mice and anti-CD44 monoclonal antibodies. Antigen-induced Th2-mediated airway
      inflammation and airway hyperresponsiveness (AHR) in sensitized mice were reduced
      by CD44-deficiency. These asthmatic responses induced by the transfer of antigen
      sensitized splenic CD4(+)  T cells from CD44-deficient mice were weaker than
      those from WT mice. Lack of CD44 failed to induce AHR by antigen challenge.
      Expression level and hyaluronic acid receptor activity of CD44, as well as Neu1
      sialidase expression on antigen-specific Th2 cells, were higher than those on
      antigen-specific Th1 cells. Anti-CD44 antibody preferentially suppressed the
      accumulation of those Th2 cells in the airway induced by antigen challenge. Our
      findings indicate that CD44 expressed on CD4(+)  T cells plays a critical role in
      the accumulation of antigen-specific Th2 cells, but not Th1 cells, in the airway
      and in the development of AHR induced by antigen challenge.

PMID- 21874649
TI  - Statins inhibit iNOS-mediated microbicidal potential of activated monocyte
      derived dendritic cells by an IFN-beta-dependent mechanism.
AB  - Statins are prescribed to 25 million people worldwide for treating
      hypercholesterolemia and reducing the risk of cardiovascular diseases. However,
      the side effects of statins on immunity, and particularly on DC immunobiology,
      have not been analyzed in-depth. Here, we have investigated the impact of
      lovastatin treatment during monocyte differentiation into DCs on the
      responsiveness of the resulting monocyte-derived DCs (moDCs) to TLR-mediated
      activation. Lovastatin positively regulated TLR4 signaling in LPS-stimulated
      moDCs, leading to strong activation of p38 MAP-kinase paralleled by increased
      proinflammatory cytokine and IFN-beta production. In contrast, lovastatin
      promoted negative regulation of IFN-beta-mediated autocrine signaling through the
      IFN-alphabeta receptor, paralleled by low expression of the transcription factor
      IRF-1, leading to the inhibition of the enzymes iNOS and HO-1. Defective
      activation of iNOS/HO-1 resulted in limited cytoprotective capacity against ROS
      and reduced microbicidal potential. These data were validated using an in vivo
      model of Listeria monocytogenes infection, which revealed that iNOS activation by
      splenic inflammatory moDCs, specialized in NO and TNF-alpha production, was
      strongly reduced in lovastatin-treated, Listeria-infected mice. Statin treatment
      could have severe implications in immunity against pathogens due to defective
      iNOS/HO-1 metabolism activation in inflammatory moDCs that might lead to immune
      failure.

PMID- 21874650
TI  - Mesenchymal stem cells expanded in human platelet lysate display a decreased
      inhibitory capacity on T- and NK-cell proliferation and function.
AB  - The use of fetal bovine serum (FBS) for the culture and expansion of mesenchymal
      stromal cells (MSCs) limits their possible clinical applications. Although some
      recent studies recommended substituting FBS with human platelet lysate (HPL) for
      the expansion of MSCs for clinical use, the functional capacity of the expanded
      cells has only been partially explored. 10% FBS and two other commercial FBS
      containing media (MesenCult and MesenPro) were compared with 10% HPL-containing
      medium for their ability to support MSCs expansion and immunomodulation. We
      demonstrate that HPL sustained MSC proliferation and expansion in vitro. However,
      the cumulative cell numbers recovered were comparable with those obtained in
      MesenPro medium. Moreover, we show that HPL alters the expression of some
      relevant MSC surface molecules, namely the DNAM-1 ligands PVR and Nectin-2, the
      NKG2D ligand ULBP3, the adhesion molecules CD49d and alphavbeta3 and the
      fibroblast-associated protein. In addition, MSCs cultured in HPL displayed
      impaired inhibitory capacity on T-cell proliferation to alloantigen and NK-cell
      proliferation and cytotoxicity. Finally, they showed decreased constitutive PGE2
      production while IL-6, IL-8 and RANTES secretion were upregulated. These results
      imply some limitations in the use of HPL for the expansion of MSCs to be used as
      immunomodulators in clinical applications.

PMID- 21874651
TI  - Enhanced IL-10 production by CD4+ T cells primed in IL-15Ralpha-deficient mice.
AB  - In this study, we investigated the functional outcomes of CD4(+)  T cells primed
      in the absence of IL-15 transpresentation. Compared with their WT counterparts
      primed in WT mice, IL-15Ralpha KO CD4(+)  T cells primed in KO mice were found to
      exclusively overproduce IL-10 upon in vitro restimulation(.)  The comparable
      expression of IL-4 and Foxp3 in CD4(+)  T cells primed in the WT and IL-15Ralpha
      KO mice indicated that this was neither due to T(H) 2- nor Treg cell
      differentiation. IL-10 overproduction was also observed when OVA-specific TCR
      transgenic CD4(+)  T (OT-II) cells were primed in KO mice, excluding an intrinsic
      deficiency of KO CD4(+)  T cells. To investigate the WT and KO microenvironment,
      DCs from both WT and IL-15Ralpha KO mice were compared. DCs from both backgrounds
      were indistinguishable in their steady-state survival and in their expression of
      MHC class II and costimulatory molecules CD80, CD86, and CD40. However, IL
      15Ralpha KO DCs primed OT-II cells in vitro to produce higher levels of IL-10
      upon their restimulation. Additionally, IL-15Ralpha KO DCs produced significantly
      more IL-10 upon activation, and IL-10 neutralization during DC-mediated in vitro
      priming abolished IL-10 overproduction by CD4(+)  T cells. Thus, IL-15Ralpha KO
      DCs provide an IL-10-enriched environment that preferentially primes CD4(+)  T
      cells for more IL-10 production, highlighting a regulatory role for IL-15
      transpresentation in CD4(+)  T-cell priming.

PMID- 21874652
TI  - Explorations of ABO-Rh antigen expressions on erythrocyte dielectrophoresis:
      changes in cross-over frequency.
AB  - A quadrupole dielectrophoretic microdevice was utilized to examine the ABO-Rh
      dependencies on erythrocyte polarizations. This important step toward medical
      microdevice technology would transform key clinical blood tests from the
      laboratory into the field. Previous work in dielectrophoretic microdevices
      demonstrated that the large number of ABO antigens on erythrocyte membranes
      impacts their dielectrophoretic signature at 1 MHz. This work explores the
      dielectrophoretic behavior of native human erythrocytes categorized by their ABO
      Rh blood types and directly compares these responses to the same erythrocyte
      sample modified to remove the A and B antigens. A beta(1-3)-galactosidase enzyme
      was utilized to cleave the ABO polysaccharide backbone at the galactosidase
      bonds. The enzymatic reaction was optimized by comparing agglutination of the
      native and modified blood cells in addition to UV-Vis and HPLC analysis of the
      reaction effluent for saccharide residues. Next, the dielectrophoretic behaviors
      of the native and modified erythrocytes were visually verified in a quadrupole
      electrode microdevice over a frequency range from 100 kHz to 80 MHz. The lower
      cross-over frequency (COF), which transitions from negative to positive
      dielectrophoresis, for ABO blood types tested (A+, A-, B+, B-, AB+, O+ and O-)
      differed over the range from 17 to 47 MHz. The COFs of the corresponding enzyme
      modified erythrocytes were also determined and the range narrowed to 29-41 MHz. A
      second COF in the 70-80 MHz range was observed and was reduced in the presence of
      the transmembrane Rhesus factor. These results suggest that antigen expression on
      erythrocyte membrane surfaces influence cell polarizations in nonuniform AC
      fields.

PMID- 21874653
TI  - Three-dimensional focusing of particles using negative dielectrophoretic force in
      a microfluidic chip with insulating microstructures and dual planar
      microelectrodes.
AB  - The focusing of biological and synthetic particles in microfluidic devices is a
      prerequisite for the construction of microstructured materials, as well as for
      medical applications. In the present study, a microdevice that can effectively
      focus particles in three dimensions using a combination of insulator-based and
      metal-electrode dielectrophoresis (DEP) has been designed and fabricated. The DEP
      force is employed to confine the particles using a negative DEP response. Four
      insulating microstructures, which form an X-pattern in the microchannel, were
      employed to distort the electric field between the insulators in a conducting
      solution, thereby generating regions with a high electric-field gradient. Two
      strips of microelectrodes on the top and bottom surfaces were placed in the
      middle of the microchannel and connected to an electric pole. Two sets of dual
      planar electrodes connected to the opposite pole were placed at the sides of the
      microchannel at the top and bottom surfaces. The results of a transient
      simulation of tracks of polystyrene particles, which was performed using the
      commercial software package CFD-ACE+ (ESI Group, France), demonstrate that the
      three-dimensional focusing of particles was achieved when the applied voltage was
      larger than 35 V at a frequency of 1 MHz. Furthermore, the focusing performance
      increased with the increased strength of the applied electric field and decreased
      inlet flow rate. Experiments on particle focusing, employing polystyrene
      particles 10 MUm in diameter, were conducted to demonstrate the feasibility of
      the proposed design; the results agree with the trend predicted by numerical
      simulations.

PMID- 21874654
TI  - Quantification of pH gradients and implications in insulator-based
      dielectrophoresis of biomolecules.
AB  - Direct current (DC) insulator-based dielectrophoretic (iDEP) microdevices have
      the potential to replace traditional alternating current dielectrophoretic
      devices for many cellular and biomolecular separation applications. The use of
      large DC fields suggest that electrode reactions and ion transport mechanisms can
      become important and impact ion distributions in the nanoliters of fluid in iDEP
      microchannels. This work tracked natural pH gradient formation in a 100 MUm wide,
      1 cm-long microchannel under applicable iDEP protein manipulation conditions.
      Using fluorescence microscopy with the pH-sensitive dye FITC Isomer I and the pH
      insensitive dye TRITC as a reference, pH was observed to drop drastically in the
      microchannels within 1 min in a 3000 V/cm electric field; pH drops were observed
      in the range of 6-10 min within a 100 V/cm electric field and varied based on the
      buffer conductivity. To address concerns of dye transport impacting intensity
      data, electrokinetic mobilities of FITC were carefully examined and found to be
      (i) toward the anode and (ii) 1 to 2 orders of magnitude smaller than H+
      transport which is responsible for pH drops from the anode toward the cathode.
      COMSOL simulations of ion transport showed qualitative agreement with
      experimental results. The results indicate that pH changes are severe enough and
      rapid enough to influence the net charge of a protein or cause aggregation during
      iDEP experiments. The results also elucidate reasonable time periods over which
      the phosphate buffering capacity can counter increases in H+ and OH- for
      unperturbed iDEP manipulations.

PMID- 21874655
TI  - Dielectrophoresis-assisted massively parallel cell pairing and fusion based on
      field constriction created by a micro-orifice array sheet.
AB  - In this paper, we present a novel electrofusion device that enables massive
      parallelism, using an electrically insulating sheet having a two-dimensional
      micro-orifice array. The sheet is sandwiched by a pair of micro-chambers with
      immersed electrodes, and each chamber is filled with the suspensions of the two
      types of cells to be fused. Dielectrophoresis, assisted by sedimentation, is used
      to position the cells in the upper chamber down onto the orifices, then the
      device is flipped over to position the cells on the other side, so that cell
      pairs making contact in the orifice are formed. When a pulse voltage is applied
      to the electrodes, most voltage drop occurs around the orifice and impressed on
      the cell membrane in the orifice. This makes possible the application of size
      independent voltage to fuse two cells in contact at all orifices exclusively in
      1:1 manner. In the experiment, cytoplasm of one of the cells is stained with a
      fluorescence dye, and the transfer of the fluorescence to the other cell is used
      as the indication of fusion events. The two-dimensional orifice arrangement at
      the pitch of 50 MUm realizes simultaneous fusion of 6 * 103 cells on a 4 mm
      diameter chip, and the fusion yield of 78-90% is achieved for various sizes and
      types of cells.

PMID- 21874656
TI  - Separation of mixtures of particles in a multipart microdevice employing
      insulator-based dielectrophoresis.
AB  - Dielectrophoresis is the electrokinetic movement of particles due to polarization
      effects in the presence of non-uniform electric fields. In insulator-based
      dielectrophoresis (iDEP) regions of low and high electric field intensity, i.e.
      non-uniformity of electric field, are produced when the cross-sectional area of a
      microchannel is decreased by the presence of electrical insulating structures
      between two electrodes. This technique is increasingly being studied for the
      manipulation of a wide variety of particles, and novel designs are continuously
      developed. Despite significant advances in the area, complex mixture separation
      and sample fractionation continue to be the most important challenges. In this
      work, a microchannel design is presented for carrying out direct current (DC)
      iDEP for the separation of a mixture of particles. The device comprises a main
      channel, two side channels and two sections of cylindrical posts with different
      diameters, which will generate different non-uniformities in the electric field
      on the main channel, designed for the discrimination and separation of particles
      of two different sizes. By applying an electric potential of 1000 V, a mixture of
      1 and 4 MUm polystyrene microspheres were dielectrophoretically separated and
      concentrated at the same time and then redirected to different outlets. The
      results obtained here demonstrate that, by carefully designing the device
      geometry and selecting operating conditions, effective sorting of particle
      mixtures can be achieved in this type of multi-section DC-iDEP devices.

PMID- 21874657
TI  - Multimodal assessment of early tumor response to chemotherapy: comparison between
      diffusion-weighted MRI, 1H-MR spectroscopy of choline and USPIO particles
      targeted at cell death.
AB  - The aim of this study was to determine the value of different magnetic resonance
      (MR) protocols to assess early tumor response to chemotherapy. We used a murine
      tumor model (TLT) presenting different degrees of response to three different
      cytotoxic agents. As shown in survival curves, cyclophosphamide (CP) was the most
      efficient drug followed by 5-fluorouracil (5-FU), whereas the etoposide treatment
      had little impact on TLT tumors. Three different MR protocols were used at 9.4
      Tesla 24 h post-treatment: diffusion-weighted (DW)-MRI, choline measurement by
      (1) H MRS, and contrast-enhanced MRI using ultrasmall iron oxide nanoparticles
      (USPIO) targeted at phosphatidylserine. Accumulation of contrast agent in
      apoptotic tumors was monitored by T(2) -weighted images and quantified by EPR
      spectroscopy. Necrosis and apoptosis were assessed by histology. Large variations
      were observed in the measurement of choline peak areas and could not be directly
      correlated to tumor response. Although the targeted USPIO particles were able to
      significantly differentiate between the efficiency of each cytotoxic agent and
      best correlated with survival endpoint, they present the main disadvantage of non
      specific tumor accumulation, which could be problematic when transferring the
      method to the clinic. DW-MRI presents a better compromise by combining
      longitudinal studies with a high dynamic range; however, DW-MRI was unable to
      show any significant effect for 5-FU. This study illustrates the need for
      multimodal imaging in assessing tumor response to treatment to compensate for
      individual limitations.

PMID- 21874658
TI  - Effects of breast cancer treatment on the hormonal and cognitive consequences of
      acute stress.
AB  - BACKGROUND: Cognitive difficulties following treatment for breast cancer are
      frequently reported. Breast cancer treatments also disrupt the function of
      ovarian and glucocorticoid hormone systems, both of which can affect cognition.
      METHODS: To assess the influence of glucocorticoid and ovarian disruption on
      cognitive dysfunction, survivors of breast cancer treated with the GnRH agonist
      Lupron were compared with healthy controls on their glucocorticoid response to a
      physiological stressor, and their performance on various measures of cognition
      including working memory, verbal paired associate memory, and narrative recall.
      RESULTS: The results indicated no significant glucocorticoid response to the
      stressor in Lupron-treated survivors, while the controls showed significantly
      elevated cortisol levels. Cognitive testing showed a general impairment of
      narrative recall in breast cancer survivors relative to controls, irrespective of
      stress treatment. When tested on an emotional narrative, controls exposed to post
      training stress showed a significant enhancement of emotional recall and a
      significant relationship between cortisol release and subsequent memory. In
      contrast, post-training stress produced no cognitive enhancement in survivors,
      and memory performance in this group showed no relationship to cortisol levels.
      CONCLUSIONS: These results suggest that a disruption of the enhancement of memory
      by stress may contribute to cognitive difficulties following breast cancer
      treatment.

PMID- 21874659
TI  - Resistive-switching crossbar memory based on Ni-NiO core-shell nanowires.
AB  - Resistive-switching memory (RRAM) is an emerging nanoscale device based on the
      localized metal-insulator transition within a few-nanometer-sized metal oxide
      region. RRAM is one of the most promising memory technologies for the ultimate
      downscaling of nonvolatile memory. However, to develop memory arrays with
      densities approaching 1 Tb cm(-2) , bottom-up schemes based on synthesis and
      assembly of metal oxide nanowires (NWs) must be demonstrated. A RRAM memory
      device based on core-shell Ni-NiO NWs is presented, in which the Ni core plays
      the role of the metallic interconnect, while the NiO shell serves as the active
      switching layer. A resistance change of at least two orders of magnitude is shown
      on electrical operation of the device, and the metal-insulator switching is
      unequivocally demonstrated to take place in the NiO shell at the crossing between
      two NWs or between a NW and a gold electrode strip. Since the fabrication of the
      NW crossbar device is not limited by lithography, this approach may provide a
      basis for high-density, low-cost crossbar memory with long-term storage
      stability.

PMID- 21874660
TI  - Commentary on uncertainty and surrogate decision making.

PMID- 21874661
TI  - Anomalous origin of the right coronary artery from the pulmonary artery.

PMID- 21874662
TI  - Left coronary artery stenosis with post-stenotic aneurysm after arterial switch
      operation before and after coronary revascularisation surgery.
AB  - We report the case of a child with severe and atypical stenosis of the left main
      coronary artery, which occurred late after arterial switch operation for
      transposition of the great arteries. Cardiac computed tomography accurately
      defined the lesion, showing the presence of post-stenotic dilation, guided the
      surgical approach and assessed coronary patency after revascularisation surgery.

PMID- 21874663
TI  - Granting you success.

PMID- 21874665
TI  - [Hyperbaric oxygenation in the treatment of patients with interstitial cystitis:
      clinical and morphological rationale].
AB  - We studied efficacy of hyperbaric oxygenation (HBO) in 8 patients with
      interstitial cystitis/painful bladder syndrome (IC/PBS). Mean age of the patients
      was 53 years (35-72 years), mean duration of the disease 7.5 years (6-17 years).
      Ulcerative IC/PBS was diagnosed in 7 of 8 patients. The patients received
      combined treatment: surgical (hydrobouginage of the bladder, electrocoagulation
      of bladder ulcer) and a HBO course in the postoperative period. The efficacy was
      assessed by clinical and morphological criteria (estimation of histamine level in
      urethral smears, proliferative activity of bladder mucosa epithelial cells). A
      HBO course consisted of 10 sessions (40 min, 2 atm). The treatment reduced the
      number of voidings for 24 hours, increased mean effective bladder volume, lowered
      a total score by L. Parsons scale, histamine content in urethral smears,
      stimulated proliferative activity of bladder mucosa epithelium. Thus, HBO proved
      its safety and effectiveness in combined treatment of IC/PBS.

PMID- 21874666
TI  - [Arterial blood flow in the prostate in the syndrome of chronic pelvic
      pain/chronic prostatitis].
AB  - Causes and mechanisms of chronic pelvic pain/chronic prostatitis (CPP/CP)
      syndrome are not well investigated yet. It is suggested that pain in an
      inflammatory form of this syndrome may be due to tissue inflammation. In the non
      inflammatory form pain may result from neurogenic factors. Standard diagnostic
      methods in the absence of inflammation often fail to detect pathological changes
      in the prostate. We made duplex mapping of the prostate and obtained quantitative
      characteristics of arterial hemodynamics of the prostate. Control values of
      arterial prostatic blood flow were developed after examination of healthy
      volunteers. These values were compared with similar values of arterial blood flow
      in CPP/CP syndrome. We found a significant decrease of the peak systolic velocity
      in patients with non-inflammatory CPP/CP syndrome. There is a direct correlation
      between intensity of pain syndrome and peak systolic velocity of arterial blood
      flow. Thus, pain may arise from chronic prostatic ischemia.

PMID- 21874667
TI  - [Transcutaneous nephrolithotripsy in presenile and senile patients].
AB  - A total of 323 transcutaneous roentgenoendoscopic operations were made in 212
      patients from January 2000 to December 2009 including 96 operations in 81
      presenile and senile patients (87 and 9 operations, respectively). Transcutaneous
      nephrolithotripsy (TCNT) eliminated concrement from the kidney for one session in
      59 (72.8%) patients. It proved to be the most sparing treatment in serious
      clinical situations and provided maximally complete evacuation of the concrement
      from the kidney. A total complication rate was 14.8%. All the complications were
      cured with conservative pharmacotherapy. TCNT has the same indications as open
      surgery, is a method of choice in presenile and senile patients with large, stag
      horn and recurrent concrements of the kidney, impacted pelvicoureteral
      concrements, in impaired renal urodynamics and high bacteriuria. TCNT can be used
      as a second-line treatment in failure of extracorporeal shock-wave lithotripsy or
      in combination with it (sandwich-therapy) for complete concrement elimination.

PMID- 21874668
TI  - [Health assessment of newborns with congenital urinary malformation].
AB  - Improvement in diagnosis of prenatal congenital urinary malformations (CUM)
      resulted in increased detection of CUM cases among newborns. To facilitate
      medical care for CUM newborns, we have developed an objective method of CUM
      newborns' health assessment. We studied 40 case histories of newborns with
      prenatally detected CUM admitted to urological clinics (20 with diagnosis of poor
      health and 20 with moderate condition severity) and 40 CUM newborns examined
      outpatiently (moderate health hazard). The computer analysis of the available
      data has established 13 most informative diagnostic criteria: 4 sonographic
      criteria, 3 lab criteria and 6 physical exam criteria estimated by 4 points -
      from 0 to 4. The criteria were pooled to a table which was used as a scale to
      assess general health condition. After delivery, CUM newborn gets inpatient
      health assessment by a neonatologist using 13 criteria. According to the total
      score, the condition is assessed as satisfactory (0-5), moderately severe (6-11),
      severe ( > 12). Efficacy of such health assessment was proved in a population
      study of 312 prenatal CUM newborns. Grouping of such newborns helps design of
      programs of further examination and management.

PMID- 21874669
TI  - [Recovery of urinary continence in patients after radical retropubic
      prostatectomy: role of nerve preservation technique].

PMID- 21874670
TI  - [Genetic monitoring of populations of Matthiola fragrans (Bunge) using RAPD and
      AFLP analysis].
AB  - The possibility of using RAPD and AFLP methods for genetic monitoring of
      populations of Matthiola fragrans (Bunge), a species included in the Red Book of
      the USSR, was shown for the first time. An analysis of inter- and intrapopulation
      and interspecies genome polymorphism was performed. Differences in the genetic
      structure of Matthiola populations from various geographical collection points
      were revealed. A simple method of performing RAPD analysis and the great number
      of unique markers found in each population compared with the AFLP analysis, as
      well as the good division of populations under statistical treatment, allow us to
      draw the conclusion that using the RAPD method in genetic monitoring of rare and
      insufficiently studied species is well founded.

PMID- 21874671
TI  - [Diversity of soil mesofauna in Northern Taiga biogeocenosises of the Kamennaya
      river basin (Karelia)].
AB  - The population of soil mesofauna in the basin of the small river subzone of the
      northern taiga (Karelia) has been investigated. It was shown that indexes of the
      number and mass of soil mesofauna in the landscape-ecological row
      ofbiogeocenosises are maximal in floodplain soils. The taxonomic composition and
      structure of domination of the soil mesofauna population depends on the location
      of biogeocenosis in the landscape: earthworms are dominants in riverine
      floodplain biogeocenosises, and larvae of elaterids and spiders prevail in the
      places outside of floodplains. The abundance of saprophytic invertebrates in
      floodplain biogeocenosises results in formation of humus of the mull type. A
      group of animals with mixed type of nutrition dominates in the places outside of
      floodplain soils that are related with humus of the moder-mor type. The
      population of rove beetles (Staphylinidae) allows the division of biogeocenosises
      into two groups according to their position in the landscape.

PMID- 21874672
TI  - [Is HIV/AIDS an independent risk factor of chronic rhinosinusitis among central
      African patients?].
AB  - OBJECTIVES: To investigate the independent effect of HIV/ AIDS in the genesis of
      acute or chronic rhinosinusitis. METHODS: This case-control study was performed
      among patients managed for chronic rhinosinusitis between January and April 2009
      the ENT and Head and Neck Department General Hospital of Kinshasa, DRCongo. Cases
      were matched with controls according to gender and age. Logic regression analysis
      served to identify factors associated with presence of chronic rhinosinusitis.
      RESULTS: The study population with 108 patients included 81 cases
      ofrhinosinusitis, 27 controls, 78 females, 30 males, 52 with HIV/AIDS and 56 HIV
      seronegatives. The mean age was 34+/-19 years (range 1 year-74 years). Only
      HIV/AIDS was identified as a significant and independent determinant of presence
      of chronic rhinosinusitis (OR= 19,6 95% CI 4,3 -88,9; P< 0,0001). CONCLUSION:
      Early ENT evaluation and continuous follow-up of HIV-infected patients are
      suggested. Age upper 20 years and high education attainment were significantly
      associated with high risk of chronic rhinosinusitis among HIV-infected patients,
      respectively.

PMID- 21874673
TI  - Subject and body in Basran Mu'tazilism, or: Mu'tazilite kalam and the fear of
      triviality.
AB  - In this paper, my aim is to offer some comment on the study of Mu'tazilite kalam,
      framed around the study of a particular episode in the Mu'tazilite dispute about
      man ('ma huwa al-insan') -- a question with a deceptively Aristotelian cadence
      that is not too difficult to dispel. Within this episode, my focus is on one of
      the major arguments used by the late Basrans to hold up their side of the dispute
      (a side heavily indebted to Abu Hashim's ontological innovations), and on the
      relationship between the mental and the physical (or the subjective and
      objective) which emerges from it. The most interesting -- and most surprising --
      aspect of this relationship is that the mental and the physical do not seem to be
      treated as distinct terms, thus creating the space for questions about how the
      two relate. The first person perspective seems to be identified with the physical
      body. My interest then is in the response of the reader to this surprising
      presentation -- or rather, in a certain kind of reader response, and thus a
      certain kind of interpretive mode, whose value and viability it is part of my aim
      to help clarify.

PMID- 21874674
TI  - Ibn Bajja on medicine and medical experience.
AB  - This article lists the medical works written by Ibn Bajja, overviews those that
      have come down to us and studies the super-commentary of Galen's commentary to
      Hippocrates' "Aphorisms (Sharh fi al-Fusul)". This text shows a deep influence of
      al-Farabi, namely in a conception of medical experience which stems from the
      latter's construal of experience (tajriba) as the inductive process described by
      Aristotle in "Posterior Analytics" which brings the premises of demonstration. On
      this basis, Ibn Bajja advocated for a less scholastic, more empiric medicine, and
      his claim was echoed by Ibn Rushd. There are some similarities between Ibn
      Bajja's text and Ibn Rushd's "K. al-Kulliyyat fi al-tibb" which suggests that the
      latter had read "Sharh fi al-Fusul". This work gives moreover some evidence that
      human dissection could have been performed during Ibn Bajja's time.

PMID- 21874675
TI  - Jocelyn Anne Rankin, PhD, FMLA, 1946-2010.

PMID- 21874676
TI  - Magical arts: the poetics of play.
AB  - The paper argues that links between play and magic in British Object Relations
      point to the persistence of aesthetic concerns within psychoanalysis. Magical
      thinking is present in British Object Relations psychoanalysis from its
      beginnings in Klein's play technique and early aesthetic writings, surfacing
      elsewhere in Susan Isaac's educational experiments and her theories of metaphor.
      Marion Milner's clinical account of the overlapping areas of illusion and symbol
      formation in a boy's war-games link the primitive rituals of Frazer's "The Golden
      Bough" with her patient's creativity. In Winnicott's concept of the transitional
      object, the theory of play achieves its apotheosis as a diffusive theory of
      culture or "private madness," and as a paradigm for psychoanalysis itself.
      Tracing the non-positivistic, mystical, and poetical elements in British Object
      Relations underlines the extent to which aesthetics is not just entangled with
      psychoanalysis, but constitutive of it in its mid-twentieth century
      manifestations.

PMID- 21874678
TI  - [Recent progress in the studies of dementia: definition of dementia from the
      stands taken by 3 Japanese psychiatric societies].

PMID- 21874677
TI  - The first formal reaction to C.G. Jung's departure from psychoanalysis: Sandor
      Ferenczi's review of "Symbols of Transformation".
AB  - Since the time when Jung and Freud severed their friendship and their collegial
      relationship, the details and the causes of the rupture have occupied both
      clinicians and scholars. The intensity of their relationship, and the pain that
      its breakdown caused them, seem to have driven much of this work, and it remains
      difficult to understand and assess the differences between them, in theory and in
      practice. In the service of assessment, we provide here an English translation of
      Sandor Ferenczi's review of the work by Jung which symbolized the break, his
      "Wandlungen und Symbole der Libido" (1911/1912). It was the first, and the most
      thorough and systematic, treatment of Jung's work, written by one of Freud's star
      followers. We also provide an introduction, which overviews the preparation for a
      psychoanalytic reply to Jung, based heavily on correspondence, and suggests the
      need to attend to the differences in clinical methodology implied in the
      different concepts of the libido held by Freud and Jung.

PMID- 21874679
TI  - [Mood disorders and dementia].

PMID- 21874680
TI  - [ACT (assertive community treatment) in Japan: results of ACT conducted in
      various areas].

PMID- 21874682
TI  - [Crisis intervention--significance of gradual intervention].

PMID- 21874681
TI  - [The role of S-ACT in curtailing the duration of hospital care].

PMID- 21874683
TI  - [Regenerative medicine, cell therapy and stem cells].

PMID- 21874684
TI  - [Keypoints in the treatment of allergic rhinitis].

PMID- 21874685
TI  - [Diagnosis and treatment of adhesive otitis media].

PMID- 21874686
TI  - Vivisecting Major: a Victorian gentleman scientist defends animal
      experimentation, 1876-1885.
AB  - Through an investigation of the public, professional, and private life of the
      Darwinian disciple George John Romanes, this essay seeks a better understanding
      of the scientific motivations for defending the practice of vivisection at the
      height of the controversy in late Victorian Britain. Setting aside a
      historiography that has tended to focus on the arguments of antivivisectionists,
      it reconstructs the viewpoint of the scientific community through an examination
      of Romanes's work to help orchestrate the defense of animal experimentation. By
      embedding his life in three complicatedly overlapping networks-the world of
      print, interpersonal communications among an increasingly professionalized body
      of scientific men, and the intimacies of private life-the essay uses Romanes as a
      lens with which to focus the physiological apprehension of the antivivisection
      movement. It is a story of reputation, self-interest, and affection.

PMID- 21874687
TI  - "Shocking" masculinity: Stanley Milgram, "obedience to authority," and the
      "crisis of manhood" in Cold War America.
AB  - Stanley Milgram's study of "obedience to authority" is one of the best-known
      psychological experiments of the twentieth century. This essay examines the
      study's special charisma through a detailed consideration of the intellectual,
      cultural, and gender contexts of Cold War America. It suggests that Milgram
      presented not a "timeless" experiment on "human nature" but, rather, a
      historically contingent, scientifically sanctioned "performance" of American
      masculinity at a time of heightened male anxiety. The essay argues that this
      gendered context invested the obedience experiments with an extraordinary
      plausibility, immediacy, and relevance. Immersed in a discourse of masculinity
      besieged, many Americans read the obedience experiments not as a fanciful study
      of laboratory brutality but as confirmation of their worst fears. Milgram's
      extraordinary success thus lay not in his "discovery" of the fragility of
      individual conscience but in his theatrical flair for staging culturally relevant
      masculine performances.

PMID- 21874688
TI  - Popularizing the ancestry of man: Robert Ardrey and the killer instinct.
AB  - This essay examines Robert Ardrey (1908-1980)-American playwright, screenwriter,
      and prolific author-as a case study in the popularization of science. Bringing
      together evidence from both paleoanthropology and ethology, Ardrey became in the
      1960s a vocal proponent of the theory that human beings are innately violent. The
      essay shows that Ardrey used his popular scientific books not only to consolidate
      a new science of human nature but also to question the popularizer's standard
      role, to reverse conventional hierarchies of scientific expertise, and to test
      the boundaries of professional scientific authority. Understanding how he did
      this can help us reassess the meanings and uses of popular science as critique in
      Cold War America. The essay also shows that E. O. Wilson's sociobiology was in
      part a reaction to the subversive political message of Ardrey's science.

PMID- 21874689
TI  - Alchemy and the history of science. Introduction.
AB  - Alchemy is part of the cultural experience of early modern Europe and yet has had
      to overcome problems of demarcation to be considered relevant to the history of
      science. This essay considers historiographical and methodological issues that
      have affected the gradual demarginalization of alchemy among attempts to explain,
      and find things out about, nature. As an area of historical study, alchemy
      relates to the history of science as part of an ensemble of practices that
      explored the natural world through natural philosophy and speculative traditions
      and by functioning as a nexus of social and intellectual life.

PMID- 21874690
TI  - Alchemy restored.
AB  - Alchemy now holds an important place in the history of science. Its current
      status contrasts with its former exile as a "pseudoscience" or worse and results
      from several rehabilitative steps carried out by scholars who made closer, less
      programmatic, and more innovative studies of the documentary sources.
      Interestingly, alchemy's outcast status was created in the eighteenth century and
      perpetuated thereafter in part for strategic and polemical reasons-and not only
      on account of a lack of historical understanding. Alchemy's return to the fold of
      the history of science highlights important features about the development of
      science and our changing understanding of it.

PMID- 21874691
TI  - What have we learned from the recent historiography of alchemy?
AB  - Over the last two decades a new scholarship on alchemy has emerged, leading to a
      fundamental reformulation of knowledge about alchemists and their activities. We
      now know that medieval and early modern alchemists employed experiment in concert
      with theory to demonstrate the existence of stable "chymical atoms," which were
      thought to combine with one another according to a hierarchical theory of matter.
      Employing laboratory-based analysis and synthesis, alchemists were among the
      first explicitly to enunciate the principle of mass balance and to show that
      materials are compounded of the ingredients into which they can be physically
      decomposed. Perhaps even more surprisingly, these convictions and practices arose
      out of the interaction of alchemical practice with scholastic Aristotelianism,
      long viewed by historians of the Scientific Revolution as antithetical to
      experiment. Thus the new historiography challenges both a long-standing
      marginalization of alchemy itself and a commonplace view of Aristotelianism as
      inimical to the early modern growth of experimental science.

PMID- 21874692
TI  - Alchemy as studies of life and matter: reconsidering the place of vitalism in
      early modern chemistry.
AB  - Early modern alchemy studied both matter and life, much like today's life
      sciences. What material life is and how it comes about intrigued alchemists. Many
      found the answer by assuming a vital principle that served as the source and
      cause of life. Recent literature has presented important cases in which vitalist
      formulations incorporated corpuscular or mechanical elements that were
      characteristic of the New Science and other cases in which vitalist thinking
      influenced important figures of the Scientific Revolution. Not merely
      speculative, vitalist ideas also motivated chymical practice. The unity of life
      science and material science that is found in many formulations of Renaissance
      alchemy disintegrated in Georg Ernst Stahl's version of post-Cartesian vitalism.

PMID- 21874693
TI  - Words and works in the history of alchemy.
AB  - This essay considers the implications of a shift in focus from ideas to practices
      in the history of alchemy. On the one hand, it is argued, this new attention to
      practice highlights the diversity of ways that early modern Europeans engaged
      alchemy, ranging from the literary to the entrepreneurial and artisanal, as well
      as the broad range of social and cultural spaces that alchemists inhabited. At
      the same time, however, recent work has demonstrated what most alchemists shared
      namely, a penchant for reading, writing, making, and doing, all at the same time.
      Any history of early modern alchemy, therefore, must attend to all of these
      practices, as well as the interplay among them. In this sense, alchemy offers a
      model for thinking and writing about early modern science more generally,
      particularly in light of recent work that has explored the intersection of
      scholarly, artisanal, and entrepreneurial forms of knowledge in the early modem
      period.

PMID- 21874694
TI  - Pursuit of the gene; from Darwin to DNA.

PMID- 21874695
TI  - Why ethics?

PMID- 21874696
TI  - Patient's page: TMJ.

PMID- 21874697
TI  - Elements of an effective dental website.

PMID- 21874698
TI  - "Mighty mouth"--how it came to be!

PMID- 21874699
TI  - Bisphosphonates, phossy jaw, and bisphosphonate-related osteonecrosis of the jaw.

PMID- 21874700
TI  - Concept, measurement and use of acculturation in health and disease risk studies.
AB  - Acculturation, a concept with its root in social science and cultural
      anthropology, is a process intimately related to health behavior and health
      status of minority populations in a multicultural society. This paper provides a
      brief review of the subject of acculturation as it relates to health research,
      showing that this concept has a potential to identify risk factors that underlie
      increased prevalence of chronic diseases, particularly in immigrant populations.
      A proper understanding of this is helpful in designing intervention programs to
      reduce the burden of such diseases and to increase the quality of life in such
      populations. The concept is defined with an outline of its history showing its
      evolution over time. Criteria for measuring acculturation are described to
      illustrate the need of accommodating its multidimensional features. Drawing
      examples from health research in US Hispanics, the role of acculturation on
      health behavior is discussed to document that the discordant findings are at
      least partially due to either use of incomplete dimensions of the concept, or not
      accounting for the dynamic aspect of its process. Finally, with illustration of a
      finding from a study among overweight Mexican American women of South Texas, a
      model of acculturation study is proposed that may be used in other immigrant
      populations undergoing the acculturation process.

PMID- 21874701
TI  - General health, psychological well-being and distress of youth immigrants in
      Italy.
AB  - In seeking to ease the rehabilitation of refugees there has generally been a
      failure to take account of the complexity of the refugees' experience of
      suffering and loss. In this their psychological and emotional well-being as well
      as the social and economic aspects of the question have frequently been of only
      peripheral concern, and the response to the psychological impact of violence has
      been primarily focused on the concept of Post-Traumatic Stress Disorder (PTSD).
      This approach assumes a pathological response to stress that is both universal
      across different cultures and centred on the potential of pathologizing coping
      strategies that might be essential not only for survival but also for
      psychological well-being.

PMID- 21874702
TI  - Influence of ethnicity, geography and climate on the variation of stature among
      Indian populations.
AB  - This paper analyzes the variation in the mean stature of adult males of a variety
      of population groups in India and examines the influence of geographical,
      climatic and ethnic factors on it. A considerable variation in mean stature has
      been found with respect to these three attributes. Variation "between" ethnic
      groups compared with "within" ethnic groups was found to be much more than that
      of geographical and climatic zones. Scheduled Castes (SC) and Scheduled Tribes
      (ST) populations have much low average height than that of General Castes (GC).
      Climatically dry and semiarid zones have a tendency to have higher stature than
      in the Monsoon areas. The mean height has been found to be the highest in north
      India. It is closely followed by west India. An interesting feature is that as
      one goes towards east and south the mean height gradually decreases. It is the
      lowest in islands. The mean heights have been regressed on geographical, climatic
      and ethnic factors, after converting these factors into binary variables. The
      regression analysis has strengthened the findings, that there is a highly
      significant relationship between height and geographical, climatic and ethnic
      factors.

PMID- 21874703
TI  - Searching the peopling of the Iberian Peninsula from the perspective of two
      andalusian subpopulations: a study based on Y-chromosome haplogroups J and E.
AB  - This study aims at a high-resolution analysis of Y-chromosome J and E haplogroups
      among Andalusians to reconstruct Neolithic, protohistorical and historical
      migrations in the Mediterranean region. Genotyping of two samples from Granada
      (n=250 males) and Huelva (n=167 males) (Spain) with Y-chromosome binary and
      microsatellite markers was performed, and the results compared with other
      Mediterranean populations. The two samples showed genetic differences that can be
      associated with different evolutionary processes. Migrations toward Andalusia
      probably originated in the Arabian Peninsula, Fertile Crescent, Balkan region and
      North Africa, and they would have predominantly occurred in protohistoric and
      historic times. Maritime travel would have notably contributed to recent gene
      flow into Iberia. This survey highlight the complexity of the Mediterranean
      migration processes and demonstrate the impact of the different population
      sources on the genetic composition of the Spanish population. The main in
      migrations to Iberia most likely did not occur through intermediate stages or, if
      such stages did occur, they would have been very few.

PMID- 21874704
TI  - Further evidence of a lower pleistocene arrival of early humans in northern
      Europe--the Untermassfeld site (Germany).
AB  - The discovery of 24 stone artifacts and two bone tools at the German fluvial site
      of Untermassfeld associated with a rich vertebrate fauna of the Epivillafranchian
      provide further evidence of a Lower Pleistocene arrival of early Homo in northern
      Europe, since results of geological, paleomagnetic and biostratigraphic
      investigations point to an absolute age of approximately 1.07 million years (ma).
      The typological study of the lithic artifacts is accompanied by the analysis of
      the mineralogical structure of the raw materials and use wear traces of simple
      flakes and retouched lithic fragments. Signs of thermal alteration on the surface
      of a stone tool may denote former exposure to fire. Hominin processing of animal
      resources is indicated by at least one knapped bone tool and bone surface
      modifications considered to be of cultural origin. Finally, lithic material from
      further archeological find sites of the Werra Valley associated with assumed
      Lower Pleistocene river sediments are discussed.

PMID- 21874705
TI  - Bone traumas in late antique populations from Croatia.
AB  - We present the results of the analyses of traumatic bone injuries in two Late
      Antique (3r to 5th century AD) skeletal samples from Croatia: Zadar--located on
      the eastern Adriatic coast, and a composite skeletal series from continental
      Croatia consisting of skeletons from Osijek, Vinkovci, Strbinci, and Zmajevac.
      The osteological series from continental Croatia are related to settlements
      located on, or near the Danubian military border, while Zadar--350 km to the
      west, is located deep in the territory of the Roman Empire. Numerous historical
      sources describe barbaric incursions, as well as large battles related to civil
      wars during the Late Antique period in continental Croatia. Conversely, there is
      no mention of similar events in the Zadar region. In accordance with these data
      our analysis tests the hypothesis that the inhabitants of continental Croatia
      were exposed to greater levels of violence than those living in Zadar. Analysis
      of bone traumas in the two series shows a similar, relatively high prevalence of
      long bone fractures in both samples, with a slightly higher frequency recorded in
      Zadar. Both series exhibit a high frequency of cranial injuries with, once again,
      higher frequencies recorded in the Zadar series. Additionally, two perimortem
      cranial fractures (one caused by a sword, the other by a blunt object) were
      observed in Zadar. Some of the recorded traumas in both samples resulted from
      accidents, but a number of injuries clearly resulted from intentional violence of
      lesser intensity. Further multidisciplinary research incorporating osteological,
      archaeological, and historical analyses is necessary to confirm the results
      obtained from these samples.

PMID- 21874706
TI  - Starvation as cause of death in the Croatian Quarnero and hinterland between 1816
      and 1825.
AB  - Our aim is to investigate starvation as cause of death and social and demographic
      consequences in the Croatian Quarnero and its hinterland between 1816 and 1825,
      paying particular attention to the infamous "year of famine" 1817. Our sources
      were: registers of births, marriages, and deaths from 21 parishes kept at the
      Croatian State Archives in Rijeka and Zagreb. We collected and processed data for
      statistical analysis according to the date of baptism (birth), marriage, and
      death, and according to sex and age. Our focus was on recorded causes of death.
      Between 1816 and 1825, 15,701 children were baptised (born), and 11,021 people
      died. Starvation was recorded as cause of death in 255 cases, of which 198 were
      recorded in the infamous 1817. It was the only year with negative growth in
      virtually all parishes, with the birth-to-death ratio of 1147:1545. In 1817, the
      proportion of death by starvation to the total death rate was 12.8% for the
      entire area, with the highest share recorded in Veprinac (33.3%), Crikvenica
      (23.3%), and Kastav (15.8%). Death by starvation was more common in men than in
      women (56.7% vs. 43.3%, respectively). Age distribution was as follows; in the
      population below 20 years of age the death rate was 42 (16.5% of total deaths),
      but the most affected age group were infants and children aged 1-4 years (69.0%)
      whereas in adult population the death rate was 213 (83.5% of total deaths) and
      the most affected group were the elderly between 60 and 69 years (26.3%).
      Analysis shows lower birth and marriage rates between 1816 and 1818, followed by
      a steep rise and a plateau with minimal variation. This study shows that the
      Croatian Quarnero and its hinterland suffered a great famine in the early 19th
      century and 1817 in particular, which had left a deep mark on local demography,
      just like in the neighbouring parts of Croatia and Europe.

PMID- 21874707
TI  - Squatting facet: a case study Dilkaya and Van-Kalesi populations in eastern
      Turkey.
AB  - Anomalies of the skeleton provide information on living conditions, cultural
      structure and health problems in ancient societies. Squatting facet is a kind of
      anomaly that forms on the surfaces where the tibia and talus articulate is the
      squatting facet states the daily activities and living style of the society. The
      aim of this study is to learn the daily activities of the medieval societies in
      the Van region through studying of squatting facets. In this study, adult
      skeletons from Dilkaya and Van Kalesi-Eski Van Sehri societies dating to the
      Medieval Age were investigated (65 tibia and 82 tali from Dilkaya, 61 tibia and
      52 tali from Van Kalesi-Eski Van Sehri). The lateral squatting facet had high
      ratios in both societies. The tibia lateral squatting facet found on females and
      males of Dilkaya was 97.2% and 96.9%, respectively, and on females and males of
      Van kalesi Eski Van Sehri was 87.5% and 89.2%, respectively. The talus lateral
      squatting facet found on females and males of Dilkaya was 72.1% and 51.3%,
      respectively, and on females and males of Van kalesi Eski Van Sehri was 91.2% and
      83.7%, respectively. The results provide an opportunity to study the relationship
      between past and modern population, and also describe the daily activity of life
      and cultural structure.

PMID- 21874708
TI  - The possibilities and limitations of direct digital radiography, ultrasound and
      computed tomography in diagnosing pleural mesotelioma.
AB  - The goal of this study was to compare the possibilities and limitations of direct
      digital radiography of the chest (DDR), the use of ultrasound of the chest (US)
      and single slice computed tomography of the chest (CT) in diagnosing pleural
      mesothelioma. The study was conducted during the course of one year, on 80
      patients who were successively referred to a specialized institution, under
      clinical suspicion of mesothelioma. The method of investigation was the
      comparison of findings, obtained by the reviewed methods of examination, with the
      pathohistologic results of a biopsy performed on each patient. The findings that
      were obtained by the enumerated methods were classified according to the
      radiologic signs that were found in each individual patient. We evaluated
      following radiological findings (signs), on each of the investigated methods:
      plaques, localized and generalized pleural thickenings, calcifications of the
      pleura, pleural effusions, parapneumonic effusions, pleural empyema, (round)
      atelectasis, pneumothorax, tumor mass or node, inflammatory infiltrate, elevation
      of the hemidiaphragm and osteolysis. The results of these were compared with
      pathohistologic findings and analyzed by means of standard statistical methods.
      The highest sensitivity was found for CT (94.4%), followed by US (92.6%), and by
      DDR (90.7%). The highest specificity was obtained with DDR (46.2%), followed by
      CT (35.5%) and US (23.8%). The comparison of these methods showed 90% diagnostic
      accuracy for DDR in relation to CT CT as an individual method best satisfied most
      of the criteria for diagnosing mesothelioma. No pathognomonic radiologic sign for
      mesothelioma was found.

PMID- 21874709
TI  - Formula and scale for body surface area estimation in high-risk infants.
AB  - Advances in medical technology and the health sciences have lead to a rapid
      increase in the prevalence and morbidity of high-risk infants with chronic or
      permanent sequels such as the birth of early preterm infants. A suitable formula
      is therefore needed for body surface area (BSA) estimation for high-risk infants
      to more accurately devise therapeutic regimes in clinical practice. A cohort
      study involving 5014 high-risk infants was conducted to develop a suitable
      formula for estimating BSA using four of the existing formulas in the literature.
      BSA of high-risk infants was calculated using the four BSA equations (Boyd-BSA,
      Dubois-BSA, Meban-BSA, Mosteller-BSA), from which a new calculation, Mean-BSA,
      was arithmetically derived as a reference BSA measure. Multiple-regression was
      performed using nonlinear least squares curve fitting corresponding to the trend
      line and the new equation, Neo-BSA, developed using Excel and SPSS 17.0. The Neo
      BSA equation was constructed as follows: Neo-BSA = 5.520 x W(0.5526) x L(0.300).
      With the assumption of the least square root relation between weight and length,
      a BSA scale using only weight was fabricated specifically for clinical
      applications where weight is more available in high-risk infant populations than
      is length. The validity of Neo-BSA was evaluated against Meban-BSA, the best of
      the four equations for high-risk infants, as there is a similarity of subjects in
      the two studies. The other formulas revealed substantial variances in BSA
      compared to Neo-BSA. This study developed a new surface area equation, Neo-BSA,
      as the most suitable formula for BSA measurement of high-risk infants in modern
      day societies, where an emerging population of newborns with shorten gestational
      ages are becoming more prevalent as a result of new advances in the health
      sciences and new development of reproductive technologies. In particular, a scale
      for 400-7000 g body weight babies derived from the Neo-BSA equation has the
      clinical advantage of using only weight as a measurement, since length is often
      not feasible as a measurement due to the newborn's body posture. Further studies
      are required to confirm our findings for the application of Neo-BSA and the BSA
      scale (based on weight) for various populations and ethnicities under different
      clinical conditions.

PMID- 21874710
TI  - Effect of management of patients with Anorexia and Bulimia nervosa on symptoms
      and impulsive behavior.
AB  - The aim of the study was to provide further and up to date information on the
      evaluation of the management of Anorexia and Bulimia nervosa at the Eating
      Disorders Unit (EDU) of the Ljubljana Psychiatric Clinic, based upon detailed
      assessment of the eating disorders specific and non specific symptoms of
      impulsive behaviors, highly correlated with these entities. 34 female patients
      with anorexia (restrictive or purgative type) and 38 female patients with Bulimia
      nervosa (purgative or non-purgative type) undergoing hospital treatment at the
      EDU were evaluated upon admission, as well as upon discharge and three and six
      months after discharge, using the Eating Disorder Questionnaire. Upon discharge a
      marked decrease in the overall symptoms was noted. The differences in symptoms
      incidences between the two groups were significantly specific for the individual
      form of eating disorder, especially upon admission, and were more pronounced in
      anorexia group. In later measurements, performed during the period of three and
      six months after discharge, a mild trend of increase in the disorder specific
      symptoms was detected in both groups, but was not statistically significant. In
      addition to binging on food, striking, quarreling and spending sprees are
      characteristics of patients with eating disorders, which in particular apply to
      the Bulimia nervosa group. Apart from the disorder specific symptoms, impulsive
      behavior was also reduced during study period, while the difference in its
      occurrence between the two groups gradually became non-significant. The
      management of patients with eating disorders at the EDU was successful in both
      groups, confirmed by an intense reduction of the disorder specific symptoms,
      impulsive behavior and increased stability recorded three and six months after
      discharge. The study strongly suggests that the effect of treatment regime for
      eating disorders can be predicted by careful assessment of the relevant symptoms
      and impulsive behavioral patterns.

PMID- 21874711
TI  - Differences in eating and lifestyle habits between first- and sixth-year medical
      students from Zagreb.
AB  - Eating and lifestyle habits of first (n=169) and sixth (n=272) year students,
      aged 18 to 26 years, attending a Medical School in Zagreb, were compared related
      to the years of study. A self-administered questionnaire created for this study
      incorporated a food frequency questionnaire. Both year students reported similar
      number of meals per day, irregular consumption of meals, skipping breakfast,
      frequency of vegetables, fruits, cereals, sweets, milk and dairy products
      consumption, body mass index (BMI) calculated from self-reported weight and
      height and alcohol consumption. Significant differences between groups were
      observed in consuming supper (p = 0.001), being on diet (p = 0.032), intake of
      supplements (p = 0.041), meat (p < 0.001), dried meat (p = 0.027), coffee and tea
      consumption (p = 0.016), physical activity (p = 0.041; p = 0.016), and smoking (p
      = 0.029). This study showed non-healthy eating arid lifestyle behavior among
      Medical School students. We observed association between the year of study, and
      some of the eating habits and lifestyle factors.

PMID- 21874712
TI  - Self-perceived body weight status and weight-control behaviors of high school
      students in a southern city of Turkey.
AB  - Defining "healthy weight" is not easy and for an adolescent with all concerns
      about newly developing physiognomy it is even harder. The aim of this study was
      to find out the frequency of obesity and the association between the body mass
      index (BMI), weight-control behaviors and self-perceived body weight status in
      high school students of a southern city of Turkey. The students from 10 schools
      were randomly selected among 46,271 students of 72 high schools in Adana from
      1999 to 2000. The response rate was 94.8% (2352/2480). The Turkish version of
      Youth Risk Behavior Survey Questionnaire (YRBSQ) was completed by the students.
      The students' weights and heights were measured. The mean age was 16.5 +/- 1.0
      years of age (range = 14-21 years). The mean BMI was 21.0 +/- 3.1, 25.5% of
      students were underweight, 65.7% were normal, 6.4% were overweight and 2.3% were
      obese (p = 0.0001). Of all students, 24.3% defined themselves as thin, 45.3% as
      normal, 24.9% as overweight and 5.5% as obese (p = 0.0001). The percentage of
      girls defining their body weight as overweight and obese was significantly higher
      than the boys (p = 0.0001). Of all students, 35.5% wanted to lose weight, 22.3%
      wanted to gain weight, 27.8% wanted to keep their current weight. Intention (p =
      0.0001) and interventions to lose weight such as going on a diet (p = 0.0001),
      provocative vomiting (p = 0.0001) and 24-hours starving (p = 0.0001) were
      significantly higher in girls than boys. Of students, 26.8% (n=620) were on a
      diet program either to lose or to keep their body weight. There was significant
      relationship between being on a diet program and intention to change body weight
      (p = 0.047). We concluded that adolescents living in Adana have relatively higher
      risk of being underweight than being obese and have unhealthy weight changing
      plans due to their misperception of their body images. Adolescents may be
      unconscious on plans and attempts to change their body weights and nutrition and
      we suggest that education on nutrition and health is required for adolescents.

PMID- 21874713
TI  - Overweight and obesity in Slovenian schoolgirls, 1991-2006.
AB  - The proportion of overweight children and adults has been growing rapidly in the
      last few years in many European and other countries. Certain consequences of
      overweight are already manifested in youth; in adulthood they are one of the main
      causes of death and several diseases. The study examined the proportion of
      overweight and obese Slovenian girls aged 7 to 18 with the use of an annually
      repeated cross-sectional study. The study lasted from 1991 to 2006 and was based
      on the body mass index according to IOTF norms. The results show that in this
      period the proportion of overweight girls increased by almost 30% (from 13.5% to
      18.8%), whereas the proportion of obese girls doubled (from 2.3% to 4.6%). The
      prevalence of overweight and obesity is highest in childhood and early
      adolescence where it is around two to three times higher than at the age of 18.

PMID- 21874714
TI  - Effects of a hyperbaric environment on subcutaneous adipose tissue topography
      (SAT-top).
AB  - The physiological reactions of the body in scuba diving situation can be
      simulated in a pressure chamber by increasing the ambient pressure. In this study
      the influence of a hyperbaric environment of 6 bar on the changes of the
      subcutaneous adipose tissue (SAT) thicknesses on different body sites in 68
      voluntary men with undersea diving experience was investigated. Measurements of
      SAT-topography (SAT-Top) were performed with the optical device Lipometer before
      and after hyperbaric exposure. We observed a significant increase of the SAT
      layers of the upper body zones, upper abdomen (+24.5%), lower abdomen (+21%) and
      front chest (+19%) after hyperbaric exposure. This increase of volume can be
      assumed to the nitrogen accumulation in fat cells at increased ambient pressures.
      In conclusion we describe for the first time in detail the influence of a
      hyperbaric environment on quantitative and topographic changes of SAT.

PMID- 21874715
TI  - Prevalence and risk factors of alcohol abuse among university students from
      eastern Croatia: questionnaire study.
AB  - The aim of the study was to examine the prevalence of alcohol abuse among
      university students in Osijek, Croatia and its possible interconnections with
      gender, year of study, repetition of year of study, faculty subject area, sources
      of financing and type of residence during study. A validated questionnaire was
      self-administered to cross-faculty representative student sample of "J. J.
      Strossmayer" University of Osiek in June 2006. General demographic data, as well
      as data on academic features and student socio-economical status were obtained.
      The Alcohol Use Disorders Identification Test (AUDIT) was used for assessing the
      extent of alcohol consumption, with cut off value of 8 indicating possible
      alcohol problems. The majority of study participants 90.9% (755/831) had tried
      alcohol at least once in their life. Among this group, 43.8% (331/755) had an
      AUDIT total score of 8 or more: 69.2% (229/331) were males and 30.8% (102/331)
      were females. Among the study participants who screened positive, 70.4% (233/331)
      responded positively to simple advice focused on the reduction of hazardous
      drinking (AUDIT 8-15), 14.5% (48/331) needed brief counseling and continued
      monitoring (AUDIT 16-19), and 15.1% (50/331) clearly warranted further diagnostic
      evaluation for alcohol dependence (AUDIT 20 and above). Significantly different
      statistical data was found within the following factors: gender, repetition of
      year of study, faculty subject area and type of residence (chi2 = 76.232, p =
      0.0000; Fisher exact test = 31.828, p = 0.0000; chi2 = 11.667, p = 0.0086 and
      chi2 = 6.639, p = 0.0362 respectively). Alcohol consumption resulting in risk
      behaviors is common among university students from eastern Croatia. These
      findings emphasize the need for comprehensive and effective preventative
      strategies directed towards student population.

PMID- 21874716
TI  - Assessment of physical fitness levels of elderly Turkish males over 60 years.
AB  - The purpose of this study was to assess the physical fitness level of independent
      living Turkish males aged from 60 to >80 years. 849 healthy and physically
      independent male adults participated in this study voluntarily. Participants
      divided into five age groups as 60-64, 65-69, 70-74, 75-79 and >80. SFT protocol
      that included six items (chair stand test, arm curl test, 2 min step test, chair
      sit and reach test, back scratch test, 8 foot up and go test), was administered
      to each participant to assess their physical fitness level. Findings from this
      study indicated that physical fitness level of participants decreased through the
      aging process. Almost in all test items of SFT 60-64 age group had better scores
      than that of the other age groups.

PMID- 21874717
TI  - Assessment of nutritional status of gastroenterology patients in Croatia.
AB  - Malnutrition is a common feature of gastroenterological diseases. In this study,
      nutritional status of the patients admitted to Department of Gastroenterology at
      University Hospital Center Zagreb was assessed. Anthropometric, dietetic,
      biochemical methods and method of Subjective Global Assessment (SGA) was used.
      The study group included 284 patients admitted to the Hospital. Malnutrition, as
      defined by SGA, was found in 61.1% of the patients, of whom 75% were moderately
      and 25% severely malnourished. Those patients classified as moderately and
      extremely malnourished by SGA were found to have statistically lower values of
      BMI, albumin, total proteins, calcium, iron, triglycerides, cholesterol, vitamin
      A and lymphocytes as compared to those who were adequately nourished. The
      prevalence of malnutrition in hospitalized patients treated at the Department of
      Gastroenterology is high. The use of nutritional screening with multiple measures
      would be important in the early identification and treatment of these patients
      and would help decrease this high prevalence.

PMID- 21874718
TI  - Relationships between physical activity and musculoskeletal disorders in former
      athletes.
AB  - The purpose of the study was to determine the prevalence and risks for
      musculoskeletal disorders (MSD) in relation to previous athletic status and
      current physical activity level in former athletes. Main anthropometric data,
      sports history, current physical activity and MSD were estimated using a
      questionnaire in 219 (148 males, 71 females) former athletes (35-75 years old)
      and 79 controls (33 males, 46 females). According to the previous participation
      in top-level sports, former athletes were divided into three groups: (a)
      endurance, n=120 (76 males, 44 females); (b) speed-power, n=57 (43 males, 14
      females); (c) team sports, n=42 (29 males, 13 females). The most prevalent MSD
      among the male and female ex-athletes were back and knee pain. The endurance ex
      athletes group (both males and females) had significantly higher risk for the
      knee problems than the control group (Odds ratio--OR 5.9, 95% CI 1.7-20.00, p <
      0.05). Team sports athletes (males and females) showed significantly higher risk
      for Achilles' tendon injuries (OR 3.19 95% CI 1.19-8.5, p < 0.05) as compared to
      controls. Back pain did not show any significant associations with previous
      physical activity and current physical activity level. Current physical activity
      was significantly associated with a lower risk for the knee and hip pain. Body
      mass index was positively associated with knee problems. In conclusion, our study
      results revealed that previous participation in enduranve sports events is
      associated with a significantly higher risk for knee problems. At the same time
      current regular physical exercise 6-11 times per month is associated with a lower
      prevalence of knee and hip problems as compared to those who exercised less than
      6 times per month.

PMID- 21874719
TI  - The impact of basic motor abilities on the specific motoricity performance in
      elite karateka.
AB  - The aim of the study was to identify motor structures that determine high
      performance in karate. The study included a group of 85 karateka aged 18-29
      years, competing as senior category athletes within the Croatian Karate Society.
      A battery of 22 motor tests (9 basic motoricity tests and 13 specific motoricity
      tests) were used. Factor analysis of the basic motor variables pointed to the
      existence of three significant factors: coordination, explosive strength and
      movement frequency; whereas factor analysis of the specific motoricity area
      indicated two significant factors, i.e., factor of technical efficiency and
      factor of specific agility. Canonical correlation analysis showed the isolated
      set of basic motor factors to significantly determine both technical efficiency
      and specific agility-mobility of the karateka, with a predominance of the
      explosive strength (force) factor, followed by the speed and coordination
      factors.

PMID- 21874720
TI  - Anthropometric and motor features of young judoists in Vojvodina.
AB  - The aim of the study was to identify differences between trained and untrained
      subjects with respect to body composition and motor abilities. Two groups of
      subjects participated in the study: young judoists (110 boys and 56 girls) and
      their untrained mates (115 boys and 60 girls), aged 11 to 16 years, all from the
      Province of Vojvodina, Serbia. Young male judoists proved significantly better
      than their untrained mates in repetitive and static strength exercises, running
      speed, whole-body coordination, and had lower subcutaneous fat tissue of the
      upper arm. Young female judoists were significantly better in repetitive
      strength, whole-body coordination and plate tapping, chest girth and stretched
      upper arm, and also had lower subcutaneous fat tissue of the upper arm and back.

PMID- 21874721
TI  - Morphological, motor and situation-motor characteristics of elite female handball
      players according to playing performance and position.
AB  - The aim of the study was to define biomotor characteristics that determine
      playing performance and position in female handball. A battery of 13 variables
      consisting of somatotype components (3 variables), basic motor abilities (5
      variables) and specific motor abilities (5 variables) were applied in a sample of
      52 elite female handball players. Differences in biomotor characteristics
      according to playing performance and position of female handball players were
      determined by use of the analysis of variance (ANOVA) and discriminative
      analysis. Study results showed the high-quality female handball players to
      predominantly differ from the less successful ones in the specific factor of
      throw strength and basic dash factor, followed by the specific abilities of
      movement without and with ball, basic coordination/agility and specific ability
      of ball manipulation, and a more pronounced mesomorphic component. Results also
      revealed the wing players to be superior in the speed of movement frequency
      (psychomotor speed), run (explosive strength) and speed of movement with ball as
      compared with players at other playing positions. Also, endomorphic component was
      less pronounced in players at the wing and back player positions as compared with
      goalkeeper and pivot positions, where endomorphic component was considerably more
      pronounced.

PMID- 21874722
TI  - Predictive impact of coronary risk factors in southern Croatia: a case control
      study.
AB  - The aim of study was to compare the impact of coronary risk factors on the
      incidence of acute myocardial infarction (MI) between Croatia, Central and
      Eastern Europe, and the rest of the world. As a part of the large international
      INTERHEART case-control study of acute MI in 52 countries (15,152 cases and
      14,820 controls) we have investigated the relationship between several known risk
      factors (smoking, history of hypertension or diabetes, waist/hip ratio, dietary
      patterns, physical activity, consumption of alcohol, blood apolipoproteins, and
      psychosocial factors) and MI among patients without previously known coronary
      heart disease in Southern Croatia. The main identified MI risk factors in
      Southern Croatia were heavy smoking (>20 cig/day; OR 3.86; 95% CI 2.31-6.46),
      diabetes mellitus (OR 2.83; 95% CI 1.58-5.23), abnormal ratio of B-100 and A-1
      apolipoproteins (OR 2.23; 95% CI 1.28-3.89), elevated waist to hip ratio (OR
      1.96; 95% CI 1.21-3.18), and arterial hypertension (OR 1.68; 95% CI 1.15-2.45).
      Protective was moderate alcohol consumption (OR 0.63; 95% CI 0.40-0.99). The
      prevalence of major MI risk factors in Croatia is similar to that in the
      surrounding countries and in the world, accounting for over 90% of the population
      attributable risk. However, physical activity, dietary and psychosocial factors
      are seemingly less important in this country, while moderate alcohol consumption
      is more protective than regionally or globally.

PMID- 21874723
TI  - Quality of life after cardiac surgery.
AB  - The aim of this study was to determine a health-related quality of life two or
      more years after a cardiac surgery using the MOS-36 item short-form health survey
      questionnaire. 330 members of "Croatian society of patients who underwent cardiac
      surgery" were asked and 196 responders, 122 men and 74 women, were included in
      survey, all of them more than two years after surgery and older than fifty years
      of age. The answers were collected by phone. Women gained better results for
      Physical Functioning (p < 0.003) and men estimated better scores for psychical
      health (p < 0.001). Our patients gained some different results in respect to the
      Croatian sample of healthy people of the same age. They declared better General
      Health (p < 0.001), less Bodily Pain (p < 0.001), but inferior Role-Emotion (p <
      0.001) and Social Functioning (p < 0.001). The estimations of QOL improving were
      comparable with the results of numerous shorter follow-ups.

PMID- 21874724
TI  - Behaviour after cardiosurgery.
AB  - Aim of this study was to estimate behavioral changes after cardiac surgery (CS).
      A questionnaire was sent by mail to 74 women and 122 men during May 2004 and the
      answers were collected by phone. For statistical analysis, the chi2-test was
      used. A common unhealthy habits before CS were inappropriate diet (80% of all
      responders), addictions to alcohol (62%) and nicotine (54%). Significantly fewer
      patients after CS continue with fatty diet (chi2 = 39.069; p < 0.001), smoking
      (chi2 = 90.286; p < 0.001) and alcohol drinking habits (chi2 = 60.667; p <
      0.001). A significant worsening of sexual life (chi2 = 91.533; p < 0.001) and
      significantly less negative influence of weather changes (chi2 = 20.821; p <
      0.001) was found after CS. Men drink more (chi2 = 16.299; p < 0.001) and smoke
      more (chi2 = 19.635; p < 0.001), have better sexual life (chi2 = 17.317; p <
      0.001), fewer sleeping disorders (chi2 = 17.334; p < 0.001) and better oral
      health (chi2 = 38.632; p < 0.001) than women. These results can be useful for
      setting up preventive measures for CVD.

PMID- 21874725
TI  - Quality of life of patients after stroke in county Osijek-Baranya.
AB  - The purpose of this prospective study was to determine quality of life of
      patients after stroke in Osijek-Baranya County. The research included 161
      patients (82 men and 79 women) who had their first acute stroke and were treated
      at Department of Neurology, Osijek University Hospital Center The Barthel Index
      (BI) was used to assess functional deficiency and SS-QOL (Stroke-Specific Quality
      of Life) questionnaire was used for self-evaluation of patients' physical and
      mental health. The first assessment was carried out in the acute phase of the
      disease, and control assessments 30, 90 and 180 days after the stroke. Mean
      Barthel Index score was higher at every successive measurement (55, 80, 95, 95).
      All BI items were statistically significant (Friedman, p < 0.001) apart from
      dressing and bowel control. BI score indicated greater dependence in women in all
      assessments except for those taken 90 days after onset of symptoms (chi2-test, p
      = 0.111). Mean values of SS-QOL for physical health were: 105.2, 98.3, 105.7,
      117.5 and for mental health: 64.24, 57.9, 64.3, 68.1. Statistically significant
      difference was present in men, both for physical health (Friedman p = 0.009) and
      total SS-QOL (Friedman p = 0.014), while in women there was no statistically
      significant difference between the measurements (Friedman p = 0.719). The
      research showed that stroke has significant influence on basic and specific daily
      life activities and interferes with the quality of life of stroke patients. Women
      have lower level of independence. Patients who live with their families make
      better evaluation of their physical and mental health.

PMID- 21874726
TI  - CT perfusion and noncontrast CT in acute ischemic stroke diagnosing--is there
      influence on early thrombolytic therapy outcome?
AB  - The objective of this study was to compare noncontrast computed tomography (NCCT)
      and computed tomography perfusion (CTP) in early diagnosis of acute ischemic
      stroke and to define influence of these diagnostic procedures on early outcome of
      thrombolytic therapy (TLTH). The study included 45 patients, 35 patients
      submitted to NCCT and CTP and 10 patients who underwent only NCCT, before CTP was
      introduced. Based on the National Institute of Health Stroke Scale (NIHSS) score
      we compared early outcome of patients who received TLTH after NCCT only (group 1)
      with the early outcome of patients who received TLTH following NCCT and CTP
      (group 2). Statistically significant difference was found in acute stroke
      diagnosing between CTP and NCCT (p = 0.002). There were no statistically
      significant differences in TLTH early outcome between group 1 and group 2. In
      conclusion, CTP should be done regulary in patients presenting with acute
      ischemic stroke symptoms. More research needs to be done in defining exact
      influence of CTP implementation on the TLTH outcome.

PMID- 21874727
TI  - A 10-year experience in the treatment of intraabdominal cerebrospinal fluid
      pseudocysts.
AB  - The aim of this retrospective study was to assess a ten-year experience in the
      treatment of rare complications of ventriculoperitoneal shunting--intraabdominal
      cerebrospinal fluid pseudocysts. At this time there are no data about incidence,
      clinical course and treatment of these complications in Croatia. Cerebrospinal
      fluid (CSF) abdominal pseudocyst is an uncommon but important complication of
      ventriculoperitoneal shunts. Retrospective data were obtained from 5 children
      with abdominal CSF pseudocysts, treated between 1996 and 2007. The incidence of
      intraabdominal CSF pseudocysts in our study is 2.9%. All patients were girls
      ranged in age from 4 to 12 years old (mean 8.8 years). In most cases etiology of
      hydrocephalus was congenital, idiopathic. Abdominal pain and distension were the
      most frequent clinical finding (4/5). Although infection has been reported as
      responsible for pseudocyst formation, we did not found it in our series.
      Laparotomy with cyst wall excision and catheter replacement was performed in 2/5
      cases, and only cyst fluid aspiration with catheter replacement in 3/5 cases.
      Recurrence of the abdominal cyst was observed in one girl who was in terminal
      stadium of anaplastic ependymoma. It is our opinion that only catheter
      replacement and cyst fluid evacuation, as one of the treatment modalities, may be
      successful, even in large CSF intraperitoneal pseudocysts.

PMID- 21874728
TI  - Real-time expression of hTERT in primary melanoma biopsies.
AB  - Skin melanoma is by far the most lethal skin cancer, it is unpredictable by
      nature and presents a severe diagnostic problem. One of the major issues in
      melanoma diagnostics is to differentiate it with confidence from a dysplastic
      nevus. Thus, the aim of this study was to evaluate hTERT expression on a spectrum
      of dermal lesions (from normal skin toprimary melanoma) in order to examine its
      possible role as a diagnostic marker in melanoma diagnostics. In this study we
      analyzed the expression of hTERT by real-time PCR on 58 freshly obtained biopsy
      samples (4 samples of normal skin, 12 dermal nevi, 23 dysplastic nevi, 19 primary
      melanomas). Our results showed slightly greater hTERT expression in dysplastic
      nevi than melanomas with major data overlap. Considering the given results, hTERT
      does not seem to be a reliable diagnostic marker for melanoma.

PMID- 21874729
TI  - In vivo osteoinductive effect and in vitro isolation and cultivation bone marrow
      mesenchymal stem cells.
AB  - Bone marrow contains cell type termed mesenchymal stem cells (MSC), first
      recognized in bone marrow by a German pathologist, Julius Cohnheim in 1867. That
      MSCs have potential to differentiate in vitro in to the various cells lines as
      osteoblast, chondroblast, myoblast and adipoblast cells lines. Aims of our study
      were to show in vivo capacity of bone marrow MSC to produce bone in surgically
      created non critical size mandible defects New Zeland Rabbits, and then in second
      part of study to isolate in vitro MSC from bone marrow, as potential cell
      transplantation model in bone regeneration. In vivo study showed new bone
      detected on 3D CT reconstruction day 30, on all 3 animals non critical size
      defects, treated with bone marrow MSC exposed to the human Bone Morphogenetic
      Protein 7 (rhBMP-7). Average values of bone mineral density (BMD), was 530
      mg/cm3, on MSC treated animals, and 553 mg/cm3 on control group of 3 animals
      where non critical size defects were treated with iliac crest autologue bone
      graft. Activity of the Alkaline Phosphatase enzyme were measurement on 0.5, 14,
      21, 30 day and increased activity were detected day 14 on animals treated with
      bone marrow MSCs compared with day 30 on iliac crest treated animals. That
      results indicates strong osteoinduction activity of the experimental bone marrow
      MSCs models exposed to the rhBMP-7 factor Comparing ALP activity, that model
      showed superiorly results than control group. That result initiates us in opinion
      that MSCs alone should be alternative for the autolologue bone transplantation
      and in vitro study we isolated singles MSCs from the bone marrow of rat's tibia
      and femora and cultivated according to the method of Maniatopoulos et all. The
      small initial colonies of fibroblast like cells were photo-documented after 2
      days of primary culture. Such isolated and cultivated MSCs in future studies will
      be exposed to the growth factors to differentiate in osteoblast and indicate
      their clinically potential as alternative for conventional medicine and autologue
      bone transplantation. That new horizons have potential to minimize surgery and
      patient donor morbidity, with more success treatment in bone regenerative and
      metabolism diseases.

PMID- 21874730
TI  - Expression of matrix metalloproteinase-1 in uterosacral ligaments tissue of women
      with genital prolapse.
AB  - Collagen metabolism is altered in the pelvic organ tissues of women with genital
      prolapse. The aim of this study was to compare collagen metabolism by measuring
      matrix metalloproteinase-1 (MMP-1) expression in uterosacral ligament tissues of
      postmenopausal women with and without genital prolapse. Uterosacral ligament
      tissues were obtained at the time of abdominal or vaginal surgery from twenty
      four patients with pelvic organ prolapse (POP) and 21 women who underwent
      gynecologic surgery for benign indications. The tissue samples were analyzed by
      immunohistochemistry. There were no differences in age, BMI and parity between
      two groups. The patients with genital prolapse demonstrated significantly higher
      occurences of MMP-1 expression compared to controls. These findings indicate that
      increased MMP-1 expression in uterosacral ligaments is associated with genital
      prolapse. Our data are consistent with the theory that increased collagen
      breakdown may play an important role in the onset and development of pelvic organ
      prolapse (POP).

PMID- 21874731
TI  - Depression, somatization and anxiety in female patients with temporomandibular
      disorders (TMD).
AB  - The aim of this research was to determine the possible differences in degrees of
      depression, somatization and anxiety between the acute and chronic female
      patients with temporomandibular disorders (TMD), and whether these differences
      exist in healthy female patients. Ninety female patients were involved in this
      research; 60 of them were TMD patients of the Dental Polyclinic, while other 30
      females came for a routine recall visit and had no problem related to TMD.
      Patients were aged 22 to 67 years, the average age being 38.5 +/- 12 years. All
      patients were asked to fill in the RDC/TMD protocol and three psychological tests
      (Emotions Profile Index, Somatization Scale and life Events Scale). Following the
      analysis of the RDC/TMD protocol and psychological tests, it was determined that
      the chronic female patients had higher depression and somatization scores in
      comparison with the acute patients (p < 0.01); the acute patients self-perceive
      higher levels of anxiety in relation to the control group; furthermore, the
      patients reporting higher levels of depression were more inclined to somatization
      and had experienced a greater number of stress events in the past six months. It
      is beyond doubt that patients suffering from the TMD's exhibit higher levels of
      depression, somatization and anxiety compared to the healthy ones, which proves
      that physiological factors may play a predisposing role in combination with
      reduced level of body tolerance to pain, and a decreased tolerance to stress.

PMID- 21874732
TI  - Psychophysical characteristics of the premenstrual period.
AB  - Aim of this study was to investigate psychophysical characteristics of the
      premenstrual period in regard to the period following menstruation.
      Psychophysical characteristics are defined as assessments of the physical state
      (fatigue, breast tenderness, bloating and lack of sleep), emotional state
      (happiness, anger, sadness, irritability, anxiety and distraction) and general
      assessments of physical attractiveness and satisfaction with oneself Diary of
      psychophysical characteristics was designed for this study as well as a socio
      demographic questionnaire and a menstrual cycle calendar. 51 healthy, non-help
      seeking women, aged 21-46 kept a diary of psychophysical characteristics a week
      before menstruation and four days one week after the onset of menstruation,
      during two menstrual cycles. The premenstrual period is characterized by the
      intensification of negative emotional states, the decline of positive emotional
      states, and the worsening of the general self-image through the decline of the
      perception of physical attractiveness and satisfaction with oneself In
      conclusion, the premenstrual period is not marked only by the mood-swings but
      also by the changes in the cognitive representation of self

PMID- 21874733
TI  - Comparative study on gene tags of the neurotransmission system in schizophrenic
      and suicidal subjects.
AB  - Schizophrenia and suicidal behaviour are sever and complex mental disorders,
      largely determined by factors of inheritance. Both disorders present pathological
      changes in the catecholamine neurotransmitter system. The study was conducted on
      three groups; a group of subjects suffering from schizophrenia, a second
      compounded by individuals who attempted suicide and a third group of
      phenotypically healthy examinees. The blood samples of schizophrenic patients as
      of those who attempted suicide were obtained at the Psychiatric Hospital "Sveti
      Ivan" in Zagreb in the year 2004. Tests were conducted on the statistic relation
      between a total of 18 SNPs within three candidate-genes of the dopamine and
      adrenergic system (DRD4, SLC6A3 and ADRA2B) and the manifestation of schzophrenia
      and suicidal behaviour. Cases were genotyped by use of SNPlex system.
      Statistically significant differences were determined in the allelic frequency
      between the mentioned groups. Findings show a significant connection between 4
      SNPs (ADRA2B rs749457, SLC6A3 rs464094, DRD4 rs11246226 and rs4331145) and
      schizophrenia, and 2 SNPs with suicidal attempt (ADRA2B rs1018351 i SLC6A3
      rs403636). In addition, this is the first study that highlights the potential
      role/effect of polymorphisms in ADRA2B on the manifestation of schizophrenia, as
      on suicidal behaviour.

PMID- 21874734
TI  - Serotonin and cortisol as suicidogenic factors in patients with PTSD.
AB  - Post-traumatic stress disorder (PTSD) frequently occurs in commorbidity with
      different mental disorders, including suicidal behaviour. Group of biological
      factors, including serotonergic system, HPA axis and some genetic factors, are
      being studied as potential markers, able to differentiate suicidal and non
      suicidal behaviour across the group of PTSD patients. This study is examining
      statistical relation between platelet serotonine concentration and serum
      cortisole concentration, within the group of PTSD patients with and without
      attempted suicide, treated at "Sveti Ivan" Psychiatric Hospital in Zagreb. The
      hypothesis of this study is that periferal biochemical markers are different
      across the groups of PTSD patients with and without attempted suicide and the
      group of healthy controls. Our results have shown significantly lower platelet
      serotonine concentration in PTSD patients with and without suicide behaviour,
      compared to healthy controls. There are no statistically significant differences
      of the serum cortisole concentration across observed groups. Our results
      correspond with those reported by other authors in this area of research,
      suggesting that platelet serotonine level might be used as potential periferal
      marker to detect risk of suicidal behaviour in PTSD patients.

PMID- 21874735
TI  - Suppurative tonsillitis and sudden cardiac death due to physical training in a
      young soccer player.
AB  - A teenager aged 17 was a professional soccer player, and was without symptoms. He
      died suddenly during physical exercise at the field. All reanimation efforts were
      unsuccessfull. At the forensic autopsy he had suppurative bacterial tonsillitis,
      subacute diffuse myopericarditis and narrowing of the ascending aorta of 10 mm.
      In Croatia the death rate among athletes reached 0.15/100,000, in athletes
      suffered of acute respiratory tract infections 0.34/100,000, in males who
      practice exercise recreatively 0.75/100,000 (p = 0.0014), in school children
      1.0/100,000 (p = 0.0010). Physical exercise is contraindicated in acute
      respiratory tract infections. Every such case has to be treated by physician.
      When to start with physical training after suppurative-bacterial tonsillitis
      depends on disappearing of clinical signs, normalization of erythrocite
      sedimentation rate; of white cell count and serum level of C-reactive protein.
      Physical exercise is contraindicated in patients suffering of myopericarditis for
      at least 6 months. When to start exercise depends on disappearing of subjective
      symptoms and normalization of clinical and laboratory findings.

PMID- 21874736
TI  - The importance of thorough preoperative diagnostics of maxillary ameloblastoma:
      report of three cases.
AB  - Ameloblastoma, especially maxillary, is a rare benign neoplasm of odontogenic
      origin. Diagnosis of significant number of lesions is usually established
      postoperatively, because ameloblastoma, especially the unicystic form, mimics
      wide range of more frequent jaw lesions. From January 1993 to December 2005,
      three cases of the maxillary ameloblastoma were surgically treated at our
      Department. The authors present clinical, radiological and pathohistological
      features of the ameloblastomas in this rare localization with special attention
      to need of accurate preoperative diagnostics.

PMID- 21874737
TI  - Emergency prehospital on-scene thoracotomy: a novel method.
AB  - The necessity for prehospital thoracotomy is rare, but can be lifesaving.
      Occasionally an emergency practitioner or surgeon coincidentally arrives at a
      trauma scene before the arrival of emergency medical teams. In such a
      circumstance, even when thoracotomy may be indicated, it is not usually performed
      in view of the lack of equipment (e.g., dissecting tools or rib retractor). We
      present a novel technique of "L" shape thoracotomy, or Thoraco-sterno
      costochondrotomy, whereby in a prehospital setting, and with minimal equipment
      (such as a penknife) a thoracotomy can be performed with adequate exposure of the
      heart and great vessels. The similarities of this pragmatic procedure are
      considered within the context of ancient Aztec and Mesoamerican thoracotomies.

PMID- 21874738
TI  - Lower lobe pulmonary tuberculosis in immunocompetent male.
AB  - We present a case of 23-year-old student misdiagnosed for two months.
      Radiological finding showed a pneumonial infiltrate of left lung lower lobe.
      Antibiotical therapy was not resulting in a radiological regression. Biopsy of
      the lung infiltrate by transthoracic computed tomography guided histology needle,
      showed granulomatous inflammation with necrosis. Bronchial aspirate received by
      bronchoscopy was positive in culture on Mycobacterium tuberculosis. After 6
      months of antituberculotic therapy advance the complete regression of lung
      infiltrate. Tuberculosis of lower lung lobe is difficult to diagnose,
      particularly in persons who are not immunocompromised or without associated
      diseases. Lower lobe localization of tuberculosis is between 0.6 to 10.5% in all
      cases. Early diagnosis and therapy of pulmonary tuberculosis depends on
      bronchoscopic samples. The biopsy of the lung infiltrate by transthoracic
      computed tomography guided histology needle in histopathological and
      bacteriological diagnosis of tuberculosis was also useful.

PMID- 21874739
TI  - Immeasurable levels of serum phosphate--an unidentified cause of respiratory
      failure in a diabetic patient.
AB  - We report a case of immeasurable levels of serum phosphate in a patient with
      juvenile type Diabetes mellitus and diabetic ketoacidosis who developed
      respiratory failure. A 27-year-old female with juvenile type insulin-dependent
      Diabetes mellitus was admitted because of suspected acute mediastinitis and
      respiratory failure, probably, among other responsible factors, caused and
      complicated by undetectable levels of serum phosphate. The serum phosphate
      concentration three days after aggressive treatment was only 0.2 mmol/L.
      Furthermore, a significant improvement in weakness and lethargy was observed. To
      the best of our knowledge, this is the first described case of immeasurable
      levels of serum phosphate. In patients with Diabetes mellitus, serum phosphate
      concentrations should be routinely checked in order to avoid additional
      complications.

PMID- 21874740
TI  - Fulminant meningococcal sepsis in a young child--a case report.
AB  - We are presenting a case of isolated fulminant meningococcal sepsis with two and
      a half year old child. Initial symptoms were obscure and common to many medical
      conditions, but also previously described as symptoms of meningococcal sepsis.
      Unrecognizing the seriousness of the condition child died at home, within few
      hours after examination and discharge from the hospital. Autopsy and
      microbiological findings unquestionably proved that the child died from septic
      shock caused by fulminant meningococcal sepsis.

PMID- 21874741
TI  - Arthroscopic treatment of localized and diffuse pigmented villonodular synovitis
      of the knee.
AB  - Pigmented villonodular synovitis (PVNS) is a rare proliferative synovial disorder
      of uncertain etiology. Two forms of this disorder, a localized (LPVNS) and
      diffuse (DPVNS) form, are well differentiated. The therapy of choice for LPVNS is
      arthroscopic partial synovectomy with excision of the lesion. Total synovectomy,
      whether done arthroscopically or through an open arthrotomy, is the recommended
      treatment for DPVNS. During an eight-year period 13 patients, six male and seven
      female, average age 28 years (range, 16 to 60 years) were treated for PVNS of the
      knee with arthroscopic synovectomy. Average follow-up was 84 months (range, 28 to
      127 months). Four patients were affected by localized PVNS and were subjected to
      partial arthroscopic synovectomy (two to three portals) with a complete lesion
      excision. The remaining nine patients presented with the diffuse form of PVNS and
      all of them underwent total arthroscopic synovectomy (five portals). The
      diagnosis was confirmed by synovial biopsy. Each patient was evaluated before
      treatment and at final follow-up. Results were assessed clinically,
      radiographically and subjectively and were rated as excellent, good, fair, or
      poor. No complications or recurrences were noted in the LPVNS group, and all four
      patients were rated as excellent. In the DPVNS group, eight patients were rated
      as excellent and one patient was rated as fair and it was the patient who
      suffered the only recurrence in our case series. No relevant complications were
      encountered. No cases of infection, joint stiffness or neurovascular lesions were
      seen. Arthroscopy has become the golden standard in treatment of LPVNS, and can
      undoubtedly give results that are as good as with open synovectomy when treating
      DPVNS, if performed by an experienced arthroscopic surgeon.

PMID- 21874743
TI  - The Croatian model of university education for health professionals.
AB  - In all European countries healthcare professions are regulated by law. In
      Croatia, the legally--regulated professions are: medicine, dentistry, pharmacy,
      nursing, physiotherapy and midwifery, as well as radiographers, occupational
      therapists and medical laboratory technicians. Current education of health
      professionals in Croatia is traditional, inadequate and poorly harmonized with
      current educational trends, as well as with requirements and directives of
      European Commission. This Croatian model for education of health professionals at
      university level follows the recommendations specified in Croatian Qualification
      Framework: (i) learning outcomes are competency-based; (ii) mobility of students
      and faculty is encouraged; (iii) the means of quality assurance are anticipated.
      The Croatian model of university education for health professionals will make
      sure that all procedures, specified in the European and Croatian Qualification
      Framework addressing recognizability of study programs, mobility, learning
      outcomes, quality assurance and reliability of required qualifications are
      successfully completed.

PMID- 21874742
TI  - Mucoepidermoid carcinoma misdiagnosed as palatal odontogenic infection: an
      overview on the differential diagnosis of palatal lesions.
AB  - Mucoepidermoid carcinoma (MEC) accounts for approximately 30% of malignant
      salivary gland tumors and approximately 30% occur in minor salivary glands. The
      palate is the most frequent localization for those arising in minor glands. A 33
      year-old male patient with MEC of the hard palate was treated as an acute
      odontogenic infection, which was not cured after tooth endodontic treatments,
      repeated incisions and antibiotics. On the hard palate ovoid, a hard painless
      mass, which had not extended over the middle palatal line, was observed. Partial
      maxillectomy was performed. A review of the literature was performed in order to
      provide a coherent overview on the differential diagnosis of palatal lesions. To
      the best of authors' knowledge, this is the first report in English literature
      describing palatal MEC misdiagnosed and treated as odontogenic infection.
      Considering the extensive list of MEC's differential diagnoses on the hard
      palate, acute odontogenic infection can now be added to that list.

PMID- 21874744
TI  - Leptospirosis: a re-emerging infection.
AB  - Leptospirosis is a re-emerging zoonotic infection. In developing countries large
      outbreaks have occurred in urban slums and following floods. Individuals from
      developed nations are also now more frequently exposed to the infection as a
      result of international travel and greater participation in certain outdoor
      recreational activities. Leptospirosis remains a diagnostic challenge since it
      often presents as a non-specific febrile event and laboratory diagnosis is still
      currently inadequate. Rapid tests may not be sufficiently sensitive in early
      disease and culture facilities are not widely available. A severe pulmonary
      haemorrhagic form of the infection is increasingly being encountered in many
      countries including Malaysia. The control of leptospirosis is largely dependent
      on general hygienic measures and rodent control. An effective human vaccine is
      still not available. There remains much that is unknown about this disease and
      there is scope and opportunity for good quality research.

PMID- 21874745
TI  - Molecular analysis of 2009 pandemic influenza A(H1N1) in Malaysia associated with
      mild and severe infections.
AB  - The 2009 pandemic influenza A(H1N1) was first detected in Malaysia in May 2009.
      It quickly spread in the general population and contributed to a number of
      influenza-like illness. The objective of the study is to characterize genetic
      changes in early Malaysian isolates of mild and severe illness of the novel
      influenza, and to compare sequences of viruses circulating in Malaysia to those
      in other countries between May to September 2009. Viral isolates of 56 mild cases
      and 10 severe (intensive care unit or fatal) cases were sequenced for
      haemagglutinin (HA) and neuraminidase (NA). Genome sequencing of the viral RNA
      was conducted on 5 isolates (3 were from fatal cases). Highly conserved sequences
      with few sporadic variations were identified in HA and NA. E374K and D222N were
      identified in 2 viral isolates from patients with severe illness. Phylogenetic
      analysis showed close genetic relatedness to the vaccine strain
      A/California/07/09 and other isolates circulating worldwide during the same
      period. Sporadic variations were identified in the viral isolates, however a
      larger sample size is required to make associations with disease severity.

PMID- 21874746
TI  - A comparative evaluation of dengue diagnostic tests based on single-acute serum
      samples for laboratory confirmation of acute dengue.
AB  - A prospective study was carried out to evaluate the sensitivity of dengue NS1
      antigen-capture ELISA in comparison with dengue virus isolation, conventional RT
      PCR and real-time RT-PCR for laboratory confirmation of acute dengue based on
      single-acute serum samples. Four primary healthcare centres were involved to
      recruit patients with clinical diagnosis of dengue illness. Patient's
      demographic, epidemiological and clinical information were collected on a
      standardized data entry form and 5 ml of venous blood was collected upon consent.
      In the laboratory, six types of laboratory tests were performed on each of the
      collected acute serum sample. Of the 558 acute serum samples collected from 558
      patients with clinical diagnosis of dengue from mid-August 2006 to March 2009,
      174 serum samples were tested positive by the dengue NS1 antigen-capture ELISA,
      77 by virus isolation, 92 by RT-PCR and 112 by real-time RT-PCR. A total of 190
      serum samples were tested positive by either one or a combination of the four
      methods whereas, only 59 serum samples were tested positive by all four methods.
      Thus, based on single-acute serum samples, 190 of the 558 patients (34.1%) were
      laboratory-confirmed acute dengue. The overall test sensitivity was 91.6%, 40.5%,
      48.4% and 58.9% for dengue NS1 antigen-capture ELISA, virus isolation,
      conventional RT-PCR and real-time RT-PCR respectively. Statistically, dengue NS1
      antigen-capture ELISA was the most sensitive and virus isolation was the least
      sensitive test for the laboratory confirmation of acute dengue based on single
      acute serum specimens. Real-time RT-PCR was significantly more sensitive than the
      conventional RT-PCR.

PMID- 21874748
TI  - An audit of reported acute transfusion reactions in Universiti Kebangsaan
      Malaysia Medical Centre.
AB  - Transfusion is an irreversible event which carries potential benefits as well as
      risk to the recipient. The objective of this study was to analyse all reported
      transfusion reactions of the year 2008 in the Blood Bank Unit of Universiti
      Kebangsaan Malaysia Medical Centre (UKMMC). This is a retrospective study that
      was carried out by retrieving data from the laboratory information system. A
      total of 27842 transfusions were documented and the total reported transfusion
      reactions were 149. The incidence of transfusion reaction was 1 in 187 of all
      transfusions (0.54%); in which 69 (0.25%) were allergic in nature and 61 (0.22%)
      were febrile non-haemolytic transfusion reactions (FNHTR). Hypotensive reactions
      were identified in 6 (0.02%) patients. There were 9 (0.03%) cases reported with
      haemoglobinuria where no serological evidence of haemolytic transfusion reaction
      (HTR) was found. One HTR (0.003%) was identified and this was due to an error in
      patient identification in the ward. Other specified reactions like transfusion
      related acute lung injury (TRALI), bacterial infections, Graft verses host
      disease (GVHD) were not reported. The highest frequency of the reactions occurred
      in the red cell transfusions which accounted for 111 cases. In conclusion, the
      incidences of transfusion reactions are low when compared to those reported by
      other centres.

PMID- 21874747
TI  - Glycated haemoglobin is a good predictor of neonatal hypoglycaemia in pregnancies
      complicated by diabetes.
AB  - We investigated the usefulness of a single value of maternal HbA1c in late
      pregnancy as a predictor for neonatal hypoglycaemia and secondly, to find the
      appropriate threshold value. A prospective analysis of the HbA1c concentration
      between 36 to 38 weeks of gestation in 150 pregnant mothers with either pre
      existing or gestational diabetes was performed. At delivery, glucose levels in
      the cord blood were analysed. Neonatal hypoglycaemia was defined as a blood sugar
      level of < 2.6 mmol/l. Receiver operator characteristic curve was constructed to
      evaluate the value of HbA1c concentration in predicting hypoglycaemia. There were
      16 foetuses who were hypoglycaemic at delivery. The area under the ROC curve for
      predicting neonatal hypoglycaemia was 0.997 with a 95% confidence interval of
      0.992 to 1, a very good prediction rate. The optimal threshold value for HbA1c in
      predicting hypoglycaemia in the foetus was 6.8% (51 mmol/mol). HbA1c level in
      late pregnancy is a good predictor for hypoglycaemia in the newborn.

PMID- 21874749
TI  - Seroprevalance of brucellosis among suspected cases in Malaysia.
AB  - Brucellosis is a zoonotic disease which can be transmitted by direct or indirect
      contact with infected animal or their products. It is an important public health
      problem but little is known on brucellosis in the Malaysian population. The aim
      of this study was to determine the presence of Brucella antibodies using
      commercial Brucella IgG and IgM ELISA kits (Vircell, SL, Barcelona Spain). A
      total of 184 sera from suspected patients were received from 16 hospitals in
      Malaysia over the years 2004 to 2009. Only 10 serum samples (5.4%) were positive
      for Brucella antibodies in which 5 showed the presence of both IgM and IgG. Most
      of the positive patients were occupationally involved with animals. This study
      suggests the seroprevalance of brucellosis among individuals who have contact
      with infected animals in Malaysia is low.

PMID- 21874751
TI  - Recurrent haemosiderotic fibrohistiocytic lipomatous lesion of the hand.
AB  - Haemosiderotic fibrohistiocytic lipomatous lesion (HFLL) is a rare lesion, with
      uncertain aetiology, occurring almost predominantly in the lower limb. The lesion
      is known to recur locally in the foot and ankle region. We report a recurrent
      HFLL affecting the hand in a 55-year-old female, after excision of a soft tissue
      swelling in the same location 2 years previously. There was no history of trauma
      and the histological appearances of the original and recurrent lesions were
      almost identical, favouring a neoplastic nature of HFLL.

PMID- 21874750
TI  - An analysis of predictive biomarkers in routine histopathological reporting of
      infiltrating ductal breast carcinoma in a tertiary hospital in Malaysia with a
      focus on limitations and directions for future development.
AB  - Predictive biomarkers such as oestrogen (ER) and progesterone (PR) receptors and
      c-erbB-2 oncoprotein have become a staple in breast cancer reports in the country
      as they increasingly play an important role in the treatment and prognosis of
      women with breast cancers. This study reviews the practice of histopathology
      reporting of these biomarkers in a Malaysian tertiary hospital setting.
      Retrospective data on demographic, pathological and biomarker profiles of
      patients with invasive ductal carcinoma who had undergone mastectomy or
      lumpectomy with axillary node clearance from 2005 to 2006 were retrieved from the
      Department of Pathology, Penang Hospital and analysed. The prevalence of ER
      positivity (55.8%), PR positivity (52.5%), c-erbB-2 oncoprotein overexpression
      (24%) and triple negativity (ER negative, PR negative, c-erbB-2 negative) (15%)
      by immunohistochemistry were comparable with other studies. Notably, c-erbB-2
      overexpression was equivocal (2+) in 15% of cases. Since about a quarter of
      equivocal (2+) cases usually show amplification by FISH, a small but certain
      percentage of patients would miss the benefit of anti-c-erbB-2 antibody therapy
      if FISH is not performed. New ASCO/CAP guidelines on the quantitation of ER and
      PR will probably increase the prevalence of ER/PR positivity, invariably leading
      to significant ramifications on the management of patients as more patients would
      be deemed eligible for endocrine therapy, as well as categorisation of triple
      negative breast cancers.

PMID- 21874752
TI  - Myeloid sarcoma of the urinary bladder with cutaneous tumour seeding after
      percutaneous suprapubic catheterization.
AB  - Myeloid sarcoma (MS) is a rare extramedullary myeloid tumour. It has been
      reported in various sites, including lymph node, bone, skin, soft tissue, various
      organs and the CNS. It may precede or occur concurrently with acute myeloid
      leukemia. Urinary bladder involvement is extremely uncommon. We report a 70-year
      old female who had MS of the urinary bladder, presented with frank and persistent
      hematuria associated with lower abdominal pain. She subsequently had tumour
      seeding in the abdominal skin via percutaneous suprapubic catheter. Tumours from
      both the urinary bladder and skin showed immature cells that were immunoreactive
      toward LCA (focal), MPO (strong), CD99 (weak) and CD117 (weak). Summary of cases
      in the literature is presented. The potential of its misdiagnosis and the useful
      markers for the diagnosis of MS are discussed.

PMID- 21874753
TI  - Nosocomial nasal myiasis in an intensive care unit.
AB  - A 73-year-old Chinese man was admitted to the Accident and Emergency Premorbid
      Ward of a local hospital in Malaysia. The patient complained of shortness of
      breath with cough and was in a semi-conscious state. He was later admitted to an
      intensive care unit (ICU) of the hospital. Six days after admission 5-6 maggots
      were recoverd from the nasal cavity. The maggots were identified as the third
      instar larvae of Lucilia cuprina Wiedmann (Diptera: Calliphoridae) based on the
      morphological characteristics. This patient was classified as having nosocomial
      myiasis. The presence of the third instar larvae indicated that the infestation
      was not more than three to four days. An adult sarcophagid identified as
      Parasarcophaga ruficornis (Fabricius) caught in the ICU where the patient was
      warded provided further evidence of the potential for the nosocomial infestation.

PMID- 21874754
TI  - Oh dear ... it's amoebic colitis.

PMID- 21874755
TI  - Heat-shock proteins in cardiovascular disease.
AB  - Heat-shock proteins (HSPs) belong to a group of highly conserved families of
      proteins expressed by all cells and organisms and their expression may be
      constitutive or inducible. They are generally considered as protective molecules
      against different types of stress and have numerous intracellular functions.
      Secretion or release of HSPs has also been described, and potential roles for
      extracellular HSPs reported. HSP expression is modulated by different stimuli
      involved in all steps of atherogenesis including oxidative stress, proteolytic
      aggression, or inflammation. Also, antibodies to HSPs may be used to monitor the
      response to different types of stress able to induce changes in HSP levels. In
      the present review, we will focus on the potential implication of HSPs in
      atherogenesis and discuss the limitations to the use of HSPs and anti-HSPs as
      biomarkers of atherothrombosis. HSPs could also be considered as potential
      therapeutic targets to reinforce vascular defenses and delay or avoid clinical
      complications associated with atherothrombosis.

PMID- 21874756
TI  - Polyamines in cancer.
AB  - Polyamines are organic cations shown to control gene expression at the
      transcriptional, posttranscriptional, and translational levels. Multiple cellular
      oncogenic pathways are involved in regulation of transcription and translation of
      polyamine-metabolizing enzymes. As a consequence of genetic alterations,
      expression levels and activities of polyamine-metabolizing enzymes change rapidly
      during tumorigenesis resulting in high levels of polyamines in many human
      epithelial tumors. This review summarizes the mechanisms of polyamine regulation
      by canonical tumor suppressor genes and oncogenes, as well as the role of
      eukaryotic initiation factor 5A (EIF5A) in cancer. The importance of research
      utilizing pharmaceutical inhibitors and cancer chemopreventive strategies
      targeting the polyamine pathway is also discussed.

PMID- 21874757
TI  - Acquired hemophilia A.
AB  - Acquired hemophilia A is a rare but often life-threatening hemorrhagic disorder
      characterized by an autoantibody directed against coagulation factor VIII. Fifty
      per cent of cases are idiopathic whereas the remaining 50% are associated with
      pregnancy, autoimmune conditions, malignancies and drugs. In this review the
      actual knowledge on diagnostic and therapeutic aspects of this disease will be
      summarized.

PMID- 21874758
TI  - Hypobetalipoproteinemia: genetics, biochemistry, and clinical spectrum.
AB  - Hypobetalipoproteinemias (HBL) represent a heterogeneous group of disorders
      characterized by reduced plasma levels of total cholesterol (TC), low density
      lipoprotein-cholesterol (LDL-C) and apolipoprotein B (apoB) below the 5th
      percentile of the distribution in the population. HBL are defined as primary or
      secondary according to the underlying causes. Primary monogenic HBL are caused by
      mutations in several known genes (APOB, PCSK9, MTP, SARA2) or mutations in genes
      not yet identified. Familial hypobetalipoproteinemia (FHBL) is the most frequent
      monogenic form of HBL with a dominant mode of inheritance. It may be due to loss
      of-function mutations in APOB or, less frequently, in PCSK9 genes. The rare
      recessive forms of primary monogenic HBL are represented by abetalipoproteinemia
      (ABL) and chylomicron retention disease (CMRD) due to mutations in MTP and SARA2
      genes, respectively. The clinical phenotype of heterozygous FHBL is usually mild,
      being frequently characterized by fatty liver. The clinical phenotype of
      homozygous FHBL, ABL, and CMRD is usually severe being characterized by
      intestinal lipid malabsorption and fat-soluble vitamin deficiency. Secondary HBL
      are due to several nongenetic factors such as diet, drugs, and disease-related
      conditions. The aim of this review is to discuss the biochemistry, genetics, and
      clinical spectrum of HBL and to provide a clinical and laboratory diagnostic
      algorithm.

PMID- 21874759
TI  - Sm peptides in differentiation of autoimmune diseases.
AB  - Systemic lupus erythematosus (SLE) and related diseases are characterized by
      circulating autoantibodies to defined intracellular targets. Among the earliest
      identified autoantibodies were those directed to components of U2-U6 small
      nuclear ribonucleoproteins (snRNPs) known as Smith (Sm) antigen, which are highly
      specific for SLE. The Sm-antigen is composed of at least nine different
      polypeptides with molecular weights ranging from 9 to 29.5 kDa (B (B1, 28 kDa),
      B' (B2, 29 kDa), N (B3, 29.5 kDa), D1 (16 kDa), D2 (16.5 kDa), D3 (18 kDa), E (12
      kDa), F (11 kDa), and G (9 kDa)). All of the nine core proteins, but most
      frequently the B and D polypeptides, are targets of the anti-Sm autoimmune
      response. However, since SmBB' and U1 specific RNPs share the cross-reactive
      epitope motif PPPGMRPP, SmD is regarded as the most SLE specific Sm-antigen. It
      has been shown that the polypeptides D1, D3, and BB' contain symmetrical
      dimethylarginine, constituting a major autoepitope within the C-terminus of SmD1
      and SmD3. Several synthetic peptides have been used for the detection of anti-Sm
      antibodies and thus for the diagnosis of SLE. Anti-Sm antibodies have been
      reported to occur later than other SLE associated autoantibodies and, on average,
      around 1 year before the clinical onset of SLE. The present review provides a
      comprehensive summary on the history of anti-Sm antibodies and their use as
      biochemical tools to study cellular processes and as biomarker in the diagnosis
      of SLE. Additionally, a meta-analysis focused on recent data analyzes the
      prevalence of anti-Sm antibodies in SLE.

PMID- 21874760
TI  - Aromatase activity and bone loss.
AB  - Aromatase is a specific component of the cytochrome P450 enzyme system that is
      responsible for the transformation of C19 androgen precursors into C18 estrogenic
      compounds. This enzyme is encoded by the CYP19A1 gene located at chromosome
      15q21.2, that is expressed in ovary and testis not only but also in many
      extraglandular sites such as the placenta, brain, adipose tissue, and bone. The
      regulation of the level and activity of aromatase determines the levels of
      estrogens that have endocrine, paracrine, and autocrine effects on target issues
      including bone. Importantly, extraglandular aromatization of circulating androgen
      precursors is the major source of estrogen not only in men (since only 15% of
      circulating estradiol is released directly by the testis) but also in women after
      the menopause. Several lines of clinical and experimental evidence now clearly
      indicate that aromatase activity and estrogen production are necessary for
      longitudinal bone growth, attainment of peak bone mass, the pubertal growth
      spurt, epiphyseal closure, and normal bone remodeling in young individuals.
      Moreover, with aging, individual differences in aromatase activity and thus in
      estrogen levels may significantly affect bone loss and fracture risk in both
      genders.

PMID- 21874761
TI  - Biochemistry of adolescent idiopathic scoliosis.
AB  - This chapter reviews the biochemical, hormonal, and hematological factors in the
      onset and development of adolescent idiopathic scoliosis (AIS), an orthopedic
      entity of unknown etiology. Briefly, AIS is defined as a lateral curvature of the
      spine combined with vertebral rotation that occurs in patients of 10 years of age
      or older until bone maturity (18-20 years of age). AIS is predominant in females.
      If untreated, the curvature could evolve with negative long-term prognosis
      including psychosocial impact, back pain, pulmonary compromise, cor pulmonale,
      and even death due to respiratory failure. Causes of the disease have been
      postulated to involve genetics, abnormal muscle, connective tissue and bone
      structures, and neuroendocrine disorders. Psychological pathways have also been
      studied. Little data, however, have been collected on bone turnover in these
      patients. Some studies demonstrated decreased bone mineral density which may be
      suggestive of increased osteoblast activity. Other studies suggested a
      correlation to abnormal platelet morphology. Alterations in the spinal muscle
      contractile function may be responsible for spinal curvature. Measurement of
      trace elements in serum revealed impaired zinc and selenium metabolism, probably
      secondary to hormonal deregulation. Subsequent endocrine studies suggested a role
      for leptin and growth hormone in AIS. Recently, a neuroendocrine hypothesis has
      been proposed. This theory involves a unique melatonin-signaling dysfunction and
      opens new frontiers in the elucidation of the pathologic mechanisms for onset and
      progression of this disease.

PMID- 21874762
TI  - [Is the rate of medical publication from Israel similar to other countries? A
      comparative study of three medical specialties].
AB  - Academic careers of individual doctors are commonly evaluated by examining the
      number and quality of authored publications. Similarly, the extent and quality of
      medical research may be assessed nationwide by measuring the number of
      publications originating from the country of interest over time. This in turn,
      may indicate on the quality of medicine practiced. To evaluate the extent and
      quality of IsraeLi publications we measured the rate and quality of medical
      publications originating from Israel for two decades in the fields of urology,
      cardiology and orthopedics, and compared the data to those of other countries.
      METHODS: Leading journals in urology, cardiology, and orthopedics were selected.
      A Medline search (http://www.ncbi.ntm.nih.gov/sites/entrez] was conducted for all
      the publications originating in Israel between the years 1990-2009 in the
      selected journals. Data from Israel was compared to those from Italy, France,
      Germany, Egypt and Turkey. The change in rate of publications was tested using
      Linear regression. The quality of publications was calculated by multiplying the
      number of publications by the relevant impact factor. RESULTS: While the urology
      publications rate in Israel increased by 32.7% in the second study decade as
      compared with the first, the urology publication rates during the same time
      period from Italy, France, Germany, Egypt and Turkey were 199%, 115%, 184%, 180%
      and 227% respectively. The regression coefficient for the urology publication
      rate was 0.51 for Israel, and 0.78, 0.95, 0.78, 0.87 and 0.97 for the other
      countries, respectively. The regression coefficient for the change in the quality
      of publications from Israel was 0.31 and 0.81, 0.75, 0.92, 0.73, and 0.92 for the
      other countries, respectively. In cardiology, the Israeli publication rate
      increased by 26% during the second study decade, whereas in the other countries
      the increments were 46%, 35%, 76%, 80% and 309% respectively. The regression
      coefficient for Israeli pubLication rate was 0.45, and 0.78, 0.54, 0.62, 0.13 and
      0.75 for the other countries, respectively. The regression coefficient of the
      quality of publications in Israel was 0.3 as opposed to 0.47, 0.36, 0.48, 0.01,
      and 0.78 respectively. The Israeli publications in orthopedics increased by 9.3%
      during the second decade compared with the first. At the same time, other
      countries increased the publication rate in orthopedics by 69%, 121%, 173%, 140%
      and 296% respectively. The regression coefficient for the publication rate in
      orthopedics was 0.02 for Israel, and 0.62, 0.64, 0.78, 0.34 and 0.71 for the
      other countries, respectively. The regression coefficient of the quality of
      publications in Israel was 0.05 as opposed to 0.67, 0.62, 0.75, 0.31, and 0.66 in
      the other countries, respectively. CONCLUSIONS: Israel lags behind Italy, France,
      Germany, Egypt and Turkey with regard to the increase of both the number and the
      quality of medical publications in urology and orthopedics. While the rate and
      quality of IsraeLi publications in cardiology surpasses those from Egypt, they
      lag in the number of publications in this medical field behind those of all the
      rest of the countries examined. In a world of rapid progress and expansion of
      medical research, Israel has been stagnant in publications in 3 medical
      specialties, rendering it inferior to other nations.

PMID- 21874763
TI  - [Magnetic resonance imaging for the diagnosis of sacroiliitis in Israel: our
      experience in the last five years].
AB  - PURPOSE: Spondyloarthropathies are characterized by inflammatory involvement of
      the sacroiliac joints [SIJ] and sacroiliitis is a diagnostic criterion for the
      disease. Magnetic resonance imaging (MRI) is considered the preferred imaging
      modality for detection and diagnosis of sacroiliitis in its early stages. We
      reviewed MRI examinations of the SIJ performed in our institution, evaluated the
      findings and the change in study prevalence along the years. METHODS: All SIJ MRI
      studies performed in our institution between 2005-2009 were evaluated in
      consensus by an intern and a muscutoskeletal staff radiologist. The following
      findings were registered: Chronic changes: erosions, bony bridges, subchondral
      sclerosis. Acute findings: bone marrow edema, contrast enhancement. Sacroitiitis
      was diagnoses based on these findings. The prevalence of SIJ MRI studies was
      calculated and compared with all musculoskeletal MRI studies performed in these
      years. RESULTS: A total of 93 SIJ MRI studies were performed between 2005-2009. A
      gradual increase in the number of studies was detected in these years. The number
      of SIJ MRI studies performed during 2009, was 8.2 times higher than in 2005,
      while the increase in musculoskeletal MRI studies was only 2.5 fold (p < 0.001).
      53 subjects (57%) were diagnosed with sacroiliitis (male/female: 25/28, average
      age: 30 years), alternative diagnosis was given in 4 cases and in the rest no
      abnormality was detected. CONCLUSIONS: SIJ MRI is highly sensitive for
      inflammatory changes of the sacroiliac joints. Awareness of the important role of
      this study for early diagnosis and treatment of spondyloarthropathies as
      expressed in a substantial rise in referrals that has dramatically increased in
      the last years.

PMID- 21874764
TI  - [Hand-assisted laparoscopic colectomy (HALC)].
AB  - INTRODUCTION: Laparoscopic colorectal resection is not common practice, despite
      its proven advantages. Hand-assisted laparoscopic colectomy (HALC) combines the
      advantages of a format laparoscopy while minimizing its limits. GOALS: A report
      of our experience in hand-assisted colorectal resections. METHODS: A prospective
      database gathering information on 100 patients who underwent HALC in our
      department between the years 2007-2009. RESULTS: The study group includes 60 men
      and 40 women. The median age is 60 years (27-88), and the median body mass index
      (BMI) is 25 (18-34). A total of 59% of patients were operated on due to
      colorectal carcinoma, 15% had a large benign polyp, and 26% colonic diverticular
      disease. Furthermore, 41% of patients underwent right hemicolectomy, 11% left
      hemicolectomy, 30% sigmoidectomy, and 18% rectal resection. The median operating
      time was 120 (60-220) minutes, and the average incision length was 6 +/- 0.06 cm.
      The conversion rate to open surgery was 5%. In the carcinoma cases, the surgical
      margins were free of tumor and the average lymph node number harvested was 12.3
      +/- 4.3. The Learning curve stabilized after 8-12 procedures. The median time to
      first bowel movement was 3 days (1-8), and the median hospital stay was 5 days (3
      26). Postoperative complications were observed in 19% of patients: anastomotic
      leak (2), ileus (2), pulmonary emboli (1), urinary retention (3), urinary tract
      infection (3), wound infection (7), and spontaneous pneumothorax (1). Incisional
      hernia was documented in 3% of patients, after an average followup of 18 +/- 4
      months. One patient died due to myocardial infarction. CONCLUSIONS: HALC is a
      safe and effective procedure that enables the preservation of the laparoscopy
      advantages, in a short operative time, and a rapid learning curve.

PMID- 21874765
TI  - [The dilemma regarding treatment of pulmonary embolism among elderly patients].
AB  - Pulmonary embolism is a medical condition associated with significant morbidity
      and mortality. However, there are serious side effects to the anticoagulation
      therapy. We report on a 97-year-old woman who was admitted to the internal
      medicine department due to dyspnea and pleuritic chest pain. In the differential
      diagnosis we considered pulmonary embolism. In this article we present the
      diagnostic and therapeutic steps according to the guidelines, and compare them to
      a hypothetical situation of a younger woman who is presented with the same
      clinical findings. We discuss the risks that are attributed to pulmonary embolism
      on the one hand, and to the anticoagulation therapy on the other hand, with
      respect to elderly patients more than 80 and 90 years old versus younger
      patients.

PMID- 21874766
TI  - [Mediastinal cancer presenting as dermatomyositis--a case report].
AB  - We present a case of a 47-year-old man with mediastinal cancer manifesting as a
      rash, myaLgia and muscle weakness, in addition to the typical laboratory test
      results and histological changes compatible with dermatomyositis. The skin and
      muscLe findings followed the relapse of cancer which responded well to a
      combination of chemo and radiation therapy. Disease prevaLence in Rambam MedicaL
      Center during the past decade is also described. Dermatmyositis is a myositis
      with cutaneous manifestations. In a significant percent of the cases it can occur
      as a paraneoplastic syndrome. It was described as coetisting with various
      cancers, mostly adenocarcinomas. The majority of the cases occur in males above
      the age of 45 years. Malignancy can occur simultaneously with dermatomyositis or
      up to 3 years thereafter. Ovarian cancer is an exception, for it can be diagnosed
      up to six years after dermatomyositis. Therefore, it is advised to perform cancer
      screening in adult patients with dermatomyositis. Screening shouLd incLude
      extensive laboratory and imaging work-up. However, the mechanisms underlying
      paraneoplastic dermatomyositis are not fully understood. A possible antigenic
      similarity between cancer cell popuLations and regenerating myoblasts is
      suggested; this can result in an autoimmune autoantibody-mediated response in
      genetically predisposed patients. Numerous laboratory and clinical
      characteristics are associated with a high risk of malignancy. An update on
      paraneoplastic dermatomyositis is provided.

PMID- 21874768
TI  - [Who will take care of the caretaker? Lifestyle recommendations for physicians].
AB  - A healthy lifestyle is the mainstay of preventive medicine. HeaLthcare personnel
      might disregard keeping a healthy diet and exercise habits, perhaps due to
      feeling protected by their own knowledge. Physicians might under-diagnose their
      own overweight status, and have been shown in some studies to display lower rates
      of healthy behaviors compared with the general population. This review presents
      the availabLe data on physicians' own lifestyle habits, and discusses the
      importance of these for both their own health, and for the benefit of their
      patients. We supply several healthy lifestyle recommendations based on national
      and international guidelines, and adapt them to the clinic and hospital settings.
      Eating a healthy diet, and performing at least 150 minutes of aerobic exercise a
      week, with additional resistance exercises 2-3 times a week, will benefit all
      caretakers--both personally and professionally.

PMID- 21874767
TI  - [The effect of the introduction of pneumococcal vaccination for adults as a
      quality measure on vaccination rates in Clalit Health Services].
AB  - BACKGROUND: The incidence of invasive pneumococcal infections in industrialized
      countries is above 50/100,000 annuaty in adults over the age of 65 years. The
      Israel Ministry of Health recommends 23-valent polysaccharide anti-pneumococcaL
      vaccination for patients with immune suppression or chronic diseases and citizens
      above the age of 65 years. METHODS: in 1.1.2008 pneumococcal vaccination for
      adults was introduced as a quality measure in CLalit Health Services (CHS). At
      the time of the introduction of pneumococcaL vaccination as a new quality measure
      in CHS, as one of 70 quality measures in community medicine, the target
      population included all CHS enrollees over 65 years of age and patients with
      specific chronic diseases. The relative weight of this quality measure within the
      set of CHS quality measures was set at 3.19%. The goal for the measure was set at
      75%. Pneumococcal vaccination was paired with the influenza vaccination campaign.
      Mandatory copayment was reduced from NIS 57 to NIS 25 for enroLLees without
      supplementary medical insurance, and from NIS 11 to NIS 5 for enrollees with
      supplementary insurance. An alert for performing pneumococcaL vaccination for the
      target population was introduced into the medical software used by all CHS
      physicians. RESULTS: During a period of two years foLLowing the introduction of
      pneumococcaL vaccination as a quality measure in CHS, approximately 400,000 CHS
      enrollees within the target population received pneumococcaL vaccination, and the
      rate of immunization increased 10-fold (with respect to August 2007). CONCLUSION:
      The introduction of pneumococcal vaccination as a quality measure in CHS, coupled
      by other managerial and service-related actions, substantially increased the
      vaccination rates.

PMID- 21874769
TI  - ["Is it safe for my baby?" acoustic exposure of diagnostic ultrasound].
AB  - As a form of energy, diagnostic ultrasound (DUS) has the potential to have
      effects on Living tissues, e.g. bioeffects. The two most likely mechanisms for
      bioeffects are heating and cavitation. Hyperthermia is considered teratogenic in
      human fetuses during the first trimester Actual temperature changes cannot be
      studied in the human fetus. The thermal index [TI) expresses the potential for
      rise in temperature at the ultrasound's focal point. The mechanical index (MI)
      indicates the potential for the ultrasound to induce inertial cavitation in
      tissues. Nevertheless, cavitation has not been documented in mammalian fetuses,
      since there is not an air-water interface, which is needed for the cavitation
      mechanism. Since an output of TI over 1.5 is a known hazard, the question is:
      What are the settings in which such hazardous exposure occurs? Our conclusions
      regarding safety of DUS, based on the data that has been available till now, are
      the following: (1) Ultrasound end-users are poorly informed regarding safety
      issues during pregnancy. Further efforts in the realm of education and training
      are needed in order to improve knowledge of end-users about the acoustic output
      of the machines and safety issues. (2) First trimester ultrasound is associated
      with negligible rise in the thermal index. (3) Increased acoustic output Levels,
      as expressed by TI levels, are reached while performing obstetrical Doppler
      studies. In particular, TI Levels may reach 1.5 and above. Doppler procedures
      should be performed with caution and should be as brief as possible during
      obstetrical ultrasound. (4) Acoustic exposure levels during 3D/4D ultrasound
      examination, as expressed by TI are comparable to the two-dimensional B-mode
      ultrasound.

PMID- 21874770
TI  - [A multi-disciplinary approach to diabetic foot patients--an organizational model
      for the treatment of leg complications in diabetic patients].
AB  - Diabetes mellitus is the major cause of non-traumatic limb amputations in the
      Western world. In the diabetic foot patient, 85% have developed a leg ulcer prior
      to limb amputation. Due to the complicated nature of therapy in such patients, a
      multi-disciplinary approach is warranted. In this review, we describe an
      organizational model which provides an immediate solution to the factors involved
      in the evolution of a diabetic foot. At the end of 2002, The Wolfson Medical
      Center administration decided to centralize the diabetic foot patients into one
      unit situated in the Department of Medicine C. Ten beds were allocated for this
      purpose and situated at the far end of the department reducing the potential
      spread of infections to the rest of the ward. With the opening of the unit, a
      multi-disciplinary team was established that included internists, orthopedists,
      vascular surgeons, diabeticians, infectious disease specialists, and a
      specialized nursing staff that acquired their expertise while working with the
      medical staff and consultants including plastic surgeons and orthotists as
      required. With the initiation of the Diabetic Foot Unit, there was a reduction of
      50% in major amputations in the unit when compared to the preceding years. During
      the years 2003-2004, the major amputation rate dropped to Less than 8%. Treatment
      of the diabetic foot patient is complex. In order to reduce the morbidity of limb
      amputation, a Diabetic Foot Unit is justified. In addition, specialized staff
      working in concert enable a synergistic effort that cannot be acquired
      individually. Most importantly, the amputation rate can be significantly reduced
      by utilizing the Diabetic Foot Unit model.

PMID- 21874771
TI  - [Vestigial structures are important to the development of the human embryo].
AB  - Vestigial structures are homologous of organs that have lost all or most of their
      original function in a species through evolution. Atavism is the recurrence of a
      trait after an absence of one or more generations due to a chance recombination
      of genes. The genome contains genes that were active in the past, but are no
      longer active. Those genes exist in all flora and fauna. Some of these disappear
      during embryonic development, but others are retained in adult Life. Those
      structures are sometimes the result of an intrauterine 'evolutionary' process.

PMID- 21874772
TI  - [On hallucinations, bizarre sensations, phantom phenomena and body-image
      disturbances].
AB  - Subjective descriptions of neuropsychological phenomena which reflect body-image
      disturbances, are well known to neurologists, psychiatrists, neuropsychologists
      and rehabilitation medicine physicians. These phenomena may accompany patients
      with mental illnesses, after brain injury or with various neuro-orthopedic
      disabilities. It is also well documented in people who are exposed to extreme
      isolation or harsh situations.

PMID- 21874773
TI  - [The Israeli recommendations for diagnosis, management, follow-up and prevention
      of colorectal cancer (CRC) in familial adenomatous polyposis].
AB  - Approximately 30% of colorectal cancers exhibit familial clustering. We recognize
      different types of polyps and polyposis syndromes that are classified according
      to the histological diagnosis. We differentiate between adenomas, hyperplastic,
      and hamartomatous polyps as well as between syndromes that are manifested by 10
      100 or above 100 polyps. Only about 1% of colorectaL cancers (CRCs) are due to
      adenomatous polyposis syndrome. It is essential to distinguish between these
      syndromes as each has a different mode of presentation, spectrum of signs and
      symptoms and cancer risk. With the knowledge that is accumulating we now have the
      tools to lower the risk of cancer by performing specific screening programs that
      are tailored to each syndrome specifically. We present the Israeli guidelines for
      management of adenomatous polyposis, based on the American and European
      experience and consensus. We outline the importance of mutti-sectorial team work
      that includes the family practitioner, gastroenterologist, pathologist, genetic
      counselor, surgeon and social worker.

PMID- 21874774
TI  - [Guidelines for diagnosis, treatment, surveillance and prevention of cancer in
      patients with familial non-adenomatous polyposis].
AB  - Approximately 30% of colorectal cancers exhibit familial clustering. Currently,
      we recognize a number of different types of polyps and polyposis syndromes that
      are classified according to the histology of the typical polyp. We differentiate
      between adenomas, hyperplastic, and hamartomatous polyps as well as between
      syndromes that are manifested by 10-100 or above 100 polyps. It is essential to
      distinguish between these syndromes as each has a different mode of presentation,
      spectrum of signs and symptoms and cancer risk associated with them. With the
      knowledge accumulating, we now have the tools to lower the risk of cancer by
      performing specific screening programs that are tailored to each syndrome. In
      these guidelines we focus on the non-adenomatous polyps, hyperplastic and
      hamartomatous polyposis syndromes. We outline the importance of multi-sector team
      work that includes the family practitioner, gastroenterologist, pathologist,
      genetic counselor, surgeon, and social worker.

PMID- 21874775
TI  - [How to present an expert medical testimony in court?].

PMID- 21874776
TI  - Preventing and treating white-spot lesions.

PMID- 21874777
TI  - Early Class III treatment with a hybrid hyrax-mentoplate combination.

PMID- 21874778
TI  - Lower molar intrusion using skeletal anchorage.

PMID- 21874779
TI  - Efficacy of a fluoride varnish in preventing white-spot lesions as measured with
      laser fluorescence.

PMID- 21874780
TI  - A device for placement of open-coil springs.

PMID- 21874781
TI  - Correction of anterior crossbite and an unesthetic smile arc in an adult patient.

PMID- 21874782
TI  - Remodeling options and solutions.

PMID- 21874783
TI  - The future of nursing.

PMID- 21874784
TI  - Chemical policy reform--nurses must say "Yes".

PMID- 21874785
TI  - 2015 is just around the corner are you prepared?

PMID- 21874786
TI  - Screening patients for PAD: early detection = treatment & intervention.

PMID- 21874787
TI  - Gerogogy in patient education--revisited.
AB  - Gerogogy in Patient Education was first printed in Home Healthcare Nurse, Volume
      14, Number 8, (1996), Lippincott. Writers Mary Pearson, M.Ed, RN- BC and Joan
      Wessman, MA. have revisited and updated the material to meet the needs of a new
      generation of health care professionals. Baby Boomers are retiring; they will
      reach their peak in 2030, with an estimated 72 million drawing social security.
      With these numbers comes an increase in services to the elderly, mostly in the
      form of medical expenditure. The problem will not only impact the financial
      system of Medicare but will have a great toll on families. How will the retirees
      remain independent in their homes? How will they learn new medical information?
      Will new health care professions be able to teach them while taking into
      consideration the physical and psychological alterations that occur with aging
      and illness? Gerogogy takes into account the person's disease process, age
      related changes, educational level and motivation. Then incorporates these
      factors into practice, utilizing the same foundations found within the nursing
      process: assessment, planning, implementation, and evaluation. As stated, the
      methods for teaching the elderly are unique and require modifications. Gerogogy
      meets these needs so individuals can remain at home while also reducing
      unnecessary medical costs.

PMID- 21874788
TI  - Snowmaggedon 2011 or why my degree in nursing should have included an emphasis in
      hotel management.

PMID- 21874789
TI  - [Common carotid arterial diameter and coronary artery disease].
AB  - The clinical significance of the diameter of common carotid artery (CCA) measured
      ultrasonographically has not been sufficiently established. The object of this
      cross-sectional study was to investigate the relationship of the ultrasonic CCA
      diameter with coronary artery disease (CAD). In the male patients (n=169, mean
      age: 61 years) who had no apparent carotid arterial stenosis and cerebrovascular
      disease, a history of CAD, current smoking, body mass index, blood pressure,
      hemoglobin A1c, serum low-density-lipoprotein cholesterol, estimated glomerular
      filtration rate and ultrasonic measures of CCA diameter were analyzed. A total of
      25 patients had a history of CAD (15%). The CCA diameters of patients with CAD
      were significantly higher than those of patients without CAD (7.9 +/- 1.0 mm and
      7.4 +/- 0.9 mm; p = 0.01). Receiver operating characteristic curve of boundary
      value of CCA diameter revealed an area under the curve to identify the patients
      with CAD (0.63, p = 0.04). When the cut off value was considered 8.5 mm, the odds
      ratio was 4.50 (95% confidence interval = 1.71-11.84, p < 0.01), and the ratio
      were not largely altered in multivariate logistic regression analyses. The CCA
      diameter may therefore serve as a useful predictive marker for CAD in men.

PMID- 21874790
TI  - [Establishment of a cut-off value for the diagnosis of acute myocardial
      infarction using a new CK-MB activity measurement reagent containing anti-MtCK
      antibody].
AB  - CK-MB is an important marker for the diagnosis of acute myocardial infarction
      (AMI). Since mitochondrial CK (MtCK) is universally present in the blood of
      healthy individuals, it is known to positively affect the measurement of CK-MB
      using the immunoinhibition method, causing false-positive results. We performed
      basic evaluation of ACCURAS AUTO CK-MB MtO, a new reagent containing anti-MtCK
      antibody that inhibits MtCK activity, and attempted to calculate a cut-off CK-MB
      level to diagnose AMI. The measurement was performed in samples submitted to the
      Clinical Laboratory of our center for the measurement of CK-MB. This method was
      confirmed to have satisfactory basic attributes concerning the reproducibility,
      linearity, lower detection limit, and effects of interfering substances. When
      2886 samples were examined using this and conventional methods, the results of
      the two methods were correlated in some but not in others. In the samples that
      showed no correlation, MtCK was demonstrated by isozyme analysis using
      electrophoresis. The AUC calculated from the ROC curve in AMI patients was 0.912
      with this method and 0.861 with the conventional method. The sensitivity and
      specificity of the new method were higher than those of the conventional method.
      The cut-off value determined by ROC analysis was 7.7 U/l using the new method and
      13.6 U/l using the conventional method, causing an increase in false-positive
      results compared with the cut off value of 25 U/l widely used for the
      conventional method to date. However, the cut-off value for the new method that
      yielded a specificity comparable to 99.1%, which is the specificity of the
      conventional method using a cut-off value of 25 U/l, was 12 U/l. With a cut-off
      value of 12 U/l, the sensitivity was improved compared with that employing the
      conventional method, and both the sensitivity and specificity became comparable
      to those of the CK-MB mass method. This method is very useful for the accurate
      measurement of CK-MB activity.

PMID- 21874791
TI  - [Influence of protamine sulfate as neutralizer of heparin on a vancomycin assay
      in serum].
AB  - Levels of vancomycin (VCM), measured with cobas 6000 c501(c501), were low when
      blood-collecting tubes for heparinized blood (SQH) were used. It was determined
      that the phenomenon was due to the effects of protamine sulfate, a heparin
      neutralizer. VCM levels decreased by approximately 10% when the concentration of
      protamine sulfate was 0.01 mg/ml, and were undetectable when the concentration
      was 0.045 mg/ml. However, the effects of protamine sulfate, with the dose being
      up to approximately twice, were not seen in the presence of heparin. There were
      no such effects if specimens in SQH were maintained at a specified volume. The
      phenomenon was characteristic of the measurement of VCM levels using c501.
      Measurements of other agents such as valproic acid, which is measured in the same
      manner as VCM, using the same equipment did not lead to the identification of any
      effect. In addition, when VCM levels were measured with reagents of INTEGRA 800,
      no effect was seen. It is difficult to elucidate the mechanisms of action, as the
      manufacturer has not provided detailed information regarding reagents. Protamine
      sulfate is estimated to partially influence the antigen-antibody reaction
      involving anti-VCM antibodies in reagents of c501. Protamine sulfate is also used
      as an injection, and, hence, the influence of the agent on VCM levels measured
      with c501 cannot be ruled out even if other blood collecting tubes are used.
      Attachment to separating mediums presents problems when measuring blood
      concentrations of drugs, but there has been no report regarding a heparin
      neutralizer, as seen in this case. This is a new influential factor that requires
      attention.

PMID- 21874792
TI  - [Clinical evaluation of insulin measuring kit not cross-react with insulin
      analogue preparations].
AB  - Clinical evaluation of insulin assay system reacting with only human insulin
      molecule (kit B) was performed by comparing it with conventional insulin assay
      system (kit A) cross-reacting with insulin analogue as well as human insulin
      preparation. In vitro, the kit B was confirmed to cross-react with only human
      insulin, not with insulin analogue preparations such as insulin aspart, lyspro
      and glargine. In non-insulin treated diabetic patients, postprandial and post
      insulin injected serum immunoreactive insulin (IRI) concentrations measured by
      kit B were almost the same as those measured by the kit A. On the other hand, in
      diabetic patients treated with insulin analogue preparations, postprandial and
      post-insulin injected serum IRI levels measured by kit B were obviously low
      compared with those by kit A. After intravenous injection of insulin analogue
      preparations (0.1 unit/kg), insulin lyspro or insulin aspart, serum IRI levels
      measured by the kit B were not increased but gradually decreased in contrast to
      the obviously increased serum IRI level measured by the kit A. From these
      results, the kit B was confirmed not to measure the insulin analogue preparations
      in vitro and in vivo.

PMID- 21874793
TI  - [Role of the clinical laboratory for patients with massive transfusion undergoing
      elective surgery].
AB  - The microvascular bleeding resulting from the dilutional coagulopathy can occur
      when patients with massive blood loss are treated by infusing a lot of
      crystalloids, colloids, and red blood cell concentrates. For the management of
      dilutional coagulopathy and the appropriate replacement therapy of with
      coagulation factors and platelets, we usually monitor the patient's course of
      with platelet count, conventional coagulation tests such as the prothrombin time,
      the activated partial prothrombin time, and the fibrinogen concentration. The
      central clinical laboratory has a responsibility for an accurate and quick report
      of these test results of patients with massive transfusion. Furthermore, use of
      point care testing is of clinical value to fulfill a clinical demand in case with
      dilutional coagulopathy.

PMID- 21874794
TI  - [Required laboratory examination and blood transfusion therapy in massive
      hemorrhage during surgery].
AB  - Massive hemorrhage during surgery often results from diluted coagulopathy due to
      loss of coagulation factors (e.g., fibrinogen), especially in cases of thoracic
      aortic aneurysm and liver transplantation. The most important issue in preventing
      massive hemorrhage during surgery is transfusion therapy for hemostasis. When
      massive hemorrhage occurred in cases of the above surgery, we measured the
      fibrinogen level in plasma, and administered cryoprecipitate or fibrinogen
      concentrate to the patient when the fibrinogen level was below 150 mg/dL. The
      hemostatic efficacy of this treatment was evaluated by counting volume of blood
      loss and number of transfusion units in comparison with cases of conventional
      treatment with fresh frozen plasma. We observed a rapid increase in plasma
      fibrinogen level and subsequent improvement in hemostasis after cryoprecipitate
      or fibrinogen concentrate was administered. The average blood loss decreased by
      30% and the average number of transfusion units was reduced about 30 to 60% when
      those agents were given to patients with severe hypofibrinogenemia during
      surgery. The number of cases of early death due to massive hemorrhage during
      surgery decreased by 75% when cryoprecipitate or fibrinogen concentrate was used.
      Thus, in patients showing hypofibrinogenemia (i.e., <150 mg/dL) during surgery,
      administration of cryoprecipitate or fibrinogen concentrate should be effective
      in establishing hemostatsis, and therefore in reducing blood loss and number of
      transfusion units. This treatment should help to improve the prognosis of
      patients in surgery, and also to decrease the use of blood products.

PMID- 21874795
TI  - [Utility of musculoskeletal ultrasonography in rheumatic diseases].
AB  - Musculoskeletal ultrasonography (MSUS) possessing grey-scale and Doppler mode has
      become an established imaging modality for the diagnosis and follow up of
      patients with rheumatic diseases. Among rheumatic diseases, rheumatoid arthritis
      (RA) has been recognized as a good disorder to examine the joint inflammation as
      known synovitis. Early diagnosis and therapeutic intervention have given good
      outcomes to patients with RA. The 2010 RA classification criteria was reported
      and early arthritis patients has been diagnosed as RA, although the diagnostic
      and discriminative abilities of the 2010 criteria are not well known in Japanese.
      In the new criteria, synovitis is detected as joint swelling or tenderness on
      physical examination. Now we have expected if MSUS were used for detection of
      true synovitis, because we have confirmed that sensitivity of synovitis detection
      by MSUS was superior to that by physical examination.

PMID- 21874796
TI  - [Pentraxin 3].
AB  - Pentraxin 3 (PTX3) is a called as 'brand-new protein in traditional family'
      because it belongs with pentraxin family included C-reactive protein(CRP) or
      serum protein A (SAP), but the clinical papers published explosively in clinical
      situation in this 3 years. Unlike CRP, PTX3 express in atherosclerotic lesion
      which involve macrophages, neutrophils, dendritic cells, or smooth muscle cells,
      predominantly. Interestingly pitavastatin suppress PTX3 gene expression mostly in
      human endothelial cells among more than 6000 human genes. Therefore, we expect
      PTX3 to be a new biomarker for inflammatory vascular disease. Recently we
      developed an ELISA system for the detection of human PTX3 in plasma. Using this
      system, we demonstrated that PTX3 predicted patients with unstable angina
      pectoris(UAP). But it remains unclear why levels of PTX3 are increased in
      patients with acute coronary syndrome (ACS). We collected blood samples directly
      from the site of plaque rupture in 114 subjects with ACS who underwent PCI with
      an aspiration catheter. In addition, we performed immunohistochemical analyses on
      ACS patients' aspirated-thrombi to identify the cellular populations expressing
      PTX3. From these results, we concluded that infiltrating neutrophils in thrombi
      represent a diagnostically important source of PTX3 in patients with ACS.

PMID- 21874797
TI  - [Parameters related to fibrinolysis and their meanings].
AB  - To accurately assess fibrinolytic activity in plasma, many different assay
      methods are employed. We divided these to three categories by their capabilities.
      The method to assay plasminogen activation potential is the first, which is
      essentially determined by the balance between tissue plasminogen activator (tPA)
      and plasminogen activator inhibitor type 1(PA-1), and could be evaluated by
      plasma levels of these molecules as well as euglobulin clot lysis time (ECLT).
      The method to assay plasmin-dependent fibrin degradation potential is the second,
      which is mainly influenced by thrombin activatable fibrinolysis inhibitor (TAFI)
      and alpha2-antiplasmin, and could be evaluated by plasma levels of these
      modifiers as well as tPA supplemented plasma clot lysis time. The method to
      estimate ongoing status of fibrinolytic reaction in-vivo is the last, which could
      be evaluated by plasma levels of FDP including D-dimer and alpha2-antiplasmin
      plasmin complex. Employing the methods in the first two categories, we may
      estimate the risk for thrombosis. Employing the methods in the last two
      categories, we may estimate the effectiveness as well as the bleeding risk of
      thrombolytic therapy. These assay methods are described together with underlying
      molecular mechanisms at each step of fibrinolytic system.

PMID- 21874799
TI  - Radiation-induced optic neuropathy.

PMID- 21874798
TI  - Extramedullary chloroma.

PMID- 21874800
TI  - Familial adenomatous polyposis coli.

PMID- 21874801
TI  - Arrested pneumatization of the skull base.

PMID- 21874802
TI  - Tracheobronchomalacia.

PMID- 21874803
TI  - Retained surgical sponge.

PMID- 21874804
TI  - Cervical tuberculous lymphadenitis.

PMID- 21874805
TI  - Diffuse B-cell lymphoma.

PMID- 21874806
TI  - Focal fibrosing mediastinitis.

PMID- 21874807
TI  - Finger sarcoidosis.

PMID- 21874808
TI  - Pelvic inflammatory disease.

PMID- 21874809
TI  - Typical renal oncocytoma.

PMID- 21874810
TI  - Middle interhemispheric holoprosencephaly with subdural hematoma.

PMID- 21874811
TI  - Multiple bone infarcts of the left femur and tibia.

PMID- 21874812
TI  - Calcific myonecrosis.

PMID- 21874813
TI  - Neutropenic colitis.

PMID- 21874814
TI  - Central nervous system lesions in Von Hippel-Lindau syndrome.

PMID- 21874815
TI  - Pilomatrixoma.

PMID- 21874816
TI  - Metastatic carcinoid of the appendix.

PMID- 21874817
TI  - Iatrogenic fistula after lumbar disc surgery.

PMID- 21874818
TI  - Syphilitic parotitis.

PMID- 21874819
TI  - Solitary fibrous tumor of the pleura.

PMID- 21874820
TI  - Ischemic gallbladder perforation.

PMID- 21874821
TI  - Ectopic parathyroid adenoma in the upper anterior mediastinum.

PMID- 21874822
TI  - Intramedullary neuroepithelial cyst of the spinal cord.

PMID- 21874823
TI  - Abnormal serum thyroid hormones concentration with healthy functional gland: a
      review on the metabolic role of thyroid hormones transporter proteins.
AB  - Laboratory findings can definitely help the patients not to enter into status,
      where the damage might be happen due to a miss-diagnosis based on clinical
      assessment alone. The secondary disease accompanied with thyroid patients should
      also carefully check out due to the interference which some diseases can cause in
      the amount of serum thyroid hormone, particularly the free thyroxin. The dilemma
      over thyroid clinical diagnosis occur due to variation on serum thyroid hormone
      which initiated by other non-thyroidal disorders which can play an important
      roles in metabolic disorders of thyroid hormone due to the alteration which occur
      on the serum level of thyroid hormone transporter proteins. The majority of serum
      thyroid hormones of up to 95-99% are bound to the carrier proteins mainly to
      Thyroxin-Binding Globulins (TBG), some transthyretin already known as pre-albumin
      and albumin which are all synthesis in the liver and any modification which alter
      their production may alter the status of thyroid hormones. It seems TBG,
      transthyretin and albumin carries 75, 20, 5% of thyroid hormones within blood
      circulation, respectively. The dilemma facing the thyroid hormones following
      disruption of thyroid hormone transporter protein synthesis originate from this
      fact that any alteration of these protein contribute to the alteration of total
      thyroid and free serum thyroid hormones which are in fact the biologically active
      form of thyroid hormones. The subsequent of latter implication result in miss
      understanding and miss-diagnosis of thyroid function tests, with possible wrongly
      thyroid clinical care, followed by undesired therapy of otherwise healthy
      thyroid.

PMID- 21874824
TI  - Biosorption kinetics of Cu (II) ions removal from aqueous solution using
      bacteria.
AB  - The present study highlights the effective removal of Cu (II) ions from synthetic
      solution using bacteria such as B. subtilis, P. aeruginosa and E. cloacae. Batch
      biosorption studies show that the biosorption of B. subtilis is effective when
      the concentration ranges from 25-200 mg L(-1). Biomass dosage, pH and the initial
      metal ion concentration have a profound effect on the biosorption process and
      this is reported in this study. In order to understand the nature of the
      biosorption process, Langmuir and Freundlich isotherm models were applied. Pseudo
      first and second order models were used to study the biosorption kinetics. The
      results show that these bacterial strains are very much suitable for the removal
      of Cu (II) ions. Being cost effective and efficient in toxic metal ion removal,
      these bacteria can be used on a large scale.

PMID- 21874825
TI  - Biodegradable tocopherol acetate as a drug carrier to prevent ureteral stent
      associated infection.
AB  - Biomaterial-centred bacterial infections present common and challenging
      complications with medical implants like ureteral stent which provide substratum
      for the biofilm formation. Hence the purpose of this study is to make
      antibacterial stent surface with biodegradable polymer (tocopherol acetate) and
      anti-infective agents (norfloxacin and metronidazole) using a modified dip
      coating procedure. This is done by impregnating the stent pieces in the anti
      infective solution (a mixture of norfloxacin-metronidazole and polymer) for
      uniform surface coating (drug-carrier-coated stents). After coating, agar
      diffusion test was performed as qualitative test to find out the sensitivity of
      coated stents against the clinical isolates, Staphylococcus epidermidis and
      Escherichia coli. Quantitative test was measured by calculating the numbers of
      adhered bacteria on coated and uncoated stents by incubating the stent pieces in
      artificial urine. Difference in the number of viable bacteria adhered on the
      surface of coated and uncoated stents were statistically calculated using chi
      square test with p < 0.05 considered significant. The stent colonising ability of
      Staphylococcus epidermidis and Escherichia coli in a controlled environment
      chamber was determined using two-challenge dose of the isolates by in vitro
      challenge test. In qualitative test, the zone of inhibition around the coated
      stents showed sensitivity against the clinical isolates. In quantitative test,
      the number of adhered bacteria on the surface of coated stents was reduced to a
      significant level (p < 0.05). The polymer, tocopherol acetate is highly
      biodegradable in nature. Due to its degrading ability in body tissues, it
      releases the anti-infective drugs at a constant and sustained rate.

PMID- 21874826
TI  - Lipid and hematological parameters in hyperleptinemic healthy Arab male youth in
      Jordan.
AB  - To analyze the influence ofhyperleptinemia on fasting lipid and hematological
      parameters in healthy Arab male youth in Jordan, this cross-sectional study was
      carried out in April 2009 on a sample of 120 students aged 18-24 years. Subjects
      were stratified by fasting leptin into two groups (control, <12.7 ng mL(-1) vs.
      hyperleptenimic, e_< 12.7 ng mL(-1)) and BMI (normal weight, < 25 kgm(-2) vs.
      overweight/obese, BMI e_< 25 kg m(-2)). Fasting serum leptin, blood glucose,
      lipid profile and hematological parameters values were determined by standard kit
      methods. Mean serum leptin concentrations were more than five times as high in
      hyperleptenemic subjects than in control subjects (p < 0.001). Compared with
      control group, significant elevations (p < 0.01) were observed in the means total
      cholesterol, LDL cholesterol and triglyceride levels of hyperleptenemic group
      whereas no significant differences was detected in HDL-cholesterol. Except the
      changes of WBC count, MCH and slightly MCHC, there were no differences between
      both groups in any other term of hematological parameters. In conclusion, changes
      in lipid variables and some hematological parameters may increase plasma
      viscosity as a step during atherosclerosis pathogenesis in male youth at risk for
      dyslipidemia and cardiovascular diseases. Thus, hyperleptinemia could be a useful
      index in identifying healthy youth male subjects but this hypothesis needs
      further investigation.

PMID- 21874827
TI  - Preparation and characterization of hair keratin/gelatin blend films.
AB  - Abstract: Keratin solution was extracted from human hairs and used as subject for
      preparation of keratin/gelatin blend films. This study was aimed to explore the
      suitable method using for keratin extraction and extend to study the blend film
      properties. The blend films were prepared by simple evaporation method. After
      homogeneously mixed between keratin and gelatin solution at different ratios, the
      solution were placed on the plates and left in an oven at 40 degrees C for 3
      days. All of the films were then analyzed for their morphology, secondary
      structures and thermal properties by using SEM, FTIR and TGA, respectively. The
      result from SEM images showed that native keratin films have the highest rough
      surface compared to other films. In addition, the smooth surface of films
      gradually increased when the gelatin content increased. Keratin blending with
      gelatin showed structural changes, especially at the absorption bands of 3300
      2900 cm(-1) as well as the amide I, II and III regions. Moreover, thermal
      properties of the keratin films were enhanced by blending with gelatin. This
      study suggested that gelatin help to improve some properties of keratin while
      still remain its strength.

PMID- 21874828
TI  - Expression of membranous epidermal growth factor receptor in colorectal
      adenocarcinoma and its correlation with clinicopathological features.
AB  - The aim of this study was to investigate the expression of membranous epidermal
      growth factor receptor in colorectal adenocarcinoma and it's correlation with
      clinicopathological features. Fifty formalin-fixed, paraffin embedded archival
      specimens of colorectal cancer were included randomly as cases.
      Immunohistochemical staining was performed to assess EGFR expression. The results
      were correlated with the clinicopathological features of colorectal tumor
      tissues. More than 1% of membranous EGFR expression was found in 24 (48%) of
      cancer specimens. The immunoreactions intensity was classified as weak, moderate
      and strong representing 2, 22 and 24%, respectively. According to multivariate
      analysis, EGFR expression was not significantly associated with age, sex, tumor
      site, stage, grade and type of tumor in cases. These results suggest that the
      assessment of EGFR expression in colorectal cancer by conventional
      immunohistochemistry has not proven its predictive value and can not be useful to
      predict about outcome of patients.

PMID- 21874829
TI  - Achieving meaningful use of electronic health records for the oncologist.

PMID- 21874830
TI  - Adverse prognostic features in chronic lymphocytic leukemia.
AB  - Patients with chronic lymphocytic leukemia (CLL) can have variable courses, from
      indolent disease to rapid progression with limited response to treatment. The Rai
      and Binet staging systems were the first to classify patients into prognostic
      categories. Newer prognostic markers that correlate with shorter time to
      progression and time to treatment include elevated serum beta2M, TK, ZAP-70, and
      CD38, as well as unmutated IgV(H). Abnormal cytogenetics are found in the
      majority of patients with CLL. Del(17p), as well as mutations of TP53, is
      associated with an aggressive clinical course and short overall survival. Nearly
      one-fifth of patients have del(11q) and have a significantly shorter median
      progression-free survival; mutations in the ATM gene, located on 11q, may also
      have adverse prognostic implications. Intermediate-risk cytogenetic findings
      include trisomy 12 and del(6q). Patients with del(17p) should be evaluated for
      novel agents and/or allogeneic stem cell transplantation in first remission.
      Patients with del(11q) require treatment with an alkylating agent in addition to
      nucleoside analogs and rituximab, and patients with trisomy 12q may express
      higher levels of CD20, thereby making the malignant cells more susceptible to
      biologic agents that target CD20. Despite advances in stratifying patients and
      improved chemoimmunotherapeutic regimens, additional research in prognostication
      and treatment is needed.

PMID- 21874831
TI  - Are prognostic factors in CLL overrated?

PMID- 21874832
TI  - Genetic abnormalities in CLL: prognostic factors--or their own disease?

PMID- 21874833
TI  - Role of radiation therapy in patients with resectable pancreatic cancer.
AB  - The 5-year overall survival of patients with pancreatic cancer is approximately
      5%, with potentially resectable disease representing the curable minority.
      Although surgical resection remains the cornerstone of treatment, local and
      distant failure rates are high after complete resection, and debate continues as
      to the appropriate adjuvant therapy. Many oncologists advocate for adjuvant
      chemotherapy alone, given that high rates of systemic metastases are the primary
      cause of patient mortality. Others, however, view locoregional failure as a
      significant contributor to morbidity and mortality, thereby justifying the use of
      adjuvant chemoradiation. As in other gastrointestinal malignancies, neoadjuvant
      chemoradiotherapy offers potential advantages in resectable patients, and
      clinical investigation of this approach has shown promising results; however,
      phase III data are lacking. Further therapeutic advances and prospective trials
      are needed to better define the optimal role of adjuvant and neoadjuvant
      treatment in patients with resectable pancreatic cancer.

PMID- 21874834
TI  - Radiation therapy in resectable/resected pancreatic adenocarcinomas: clearing up
      the fog.

PMID- 21874835
TI  - Treatment of acute promyelocytic leukemia without cytotoxic chemotherapy.
AB  - The introduction of all-trans retinoic acid, or ATRA, in 1985, combined with
      anthracycline-based chemotherapy, has transformed acute promyelocytic leukemia
      (APL) from a fatal disease to one that is now highly curable. With appropriate
      contemporary therapy, more than 90% of patients achieve complete remission, and
      cure rates of approximately 80% and higher response and survival rates can be
      expected for patients at low and intermediate risk. The introduction of arsenic
      trioxide, or ATO, in 1994 has provided the opportunity to minimize and even
      eliminate standard cytotoxic chemotherapy from initial treatment regimens without
      compromising the excellent outcomes achieved by anthracycline-containing
      protocols. APL is a unique subtype of acute myeloid leukemia that is curable with
      targeted therapies and potentially without exposure to conventional DNA-damaging
      chemotherapy. The omission of conventional cytotoxic chemotherapy may reduce long
      term complications such as cardiomyopathy and therapy-related myelodysplastic
      syndromes. Cure rates of APL may be further increased by adopting management
      strategies to reduce early hemorrhagic deaths, which now appear to be the major
      cause of treatment failure.

PMID- 21874836
TI  - Acute promyelocytic leukemia can be treated successfully without cytotoxic
      chemotherapy.

PMID- 21874837
TI  - Arsenic trioxide in the management of APL: proceed with caution.

PMID- 21874838
TI  - Liver transplantation for the treatment of hepatocellular carcinoma.
AB  - The rise of infection with hepatitis C virus worldwide and the lack of effective
      treatment for this infection has led to a rise in the incidence of hepatocellular
      carcinoma (HCC). Moreover, it is now accepted that the cirrhotic liver,
      regardless of etiology, is a nidus for tumor formation. A landmark study of 60
      patients by Mazzaferro et al, published in 1996, forever changed the way in which
      surgeons approach this disease. The Milan criteria (one lesion <5 cm or three
      lesions < 3 cm each) were adopted by the United Network for Organ Sharing in 2002
      as the criteria by which patients would be given exception points for liver
      transplantation for HCC. Resection for HCC in the cirrhotic patient has poor
      outcomes, and many patients' livers cannot be resected due to underlying portal
      hypertension and thrombocytopenia. Results of transplantation are excellent, with
      an 80% 5-year survival. Finally, it has been demonstrated that the use of
      sirolimus for immunosuppression management in these patients may improve long
      term disease-free survival; however, no consensus has been reached across the
      transplant community.

PMID- 21874839
TI  - Transplantation or resection for hepatocellular carcinoma: biology determines
      outcome.

PMID- 21874840
TI  - Transplantation for hepatocellular carcinoma as part of a balanced,
      multidisciplinary strategy.

PMID- 21874841
TI  - [Parasitism and ecological parasitology].
AB  - Parasitism as one of the life modes is a general biological phenomenon and is a
      characteristic of all viruses, many taxa of bacteria, fungi, protists,
      metaphytes, and metazoans. Zooparasitology is focused on studies of parasitic
      animals, particularly, on their taxonomy, anatomy, life cycles, host-parasite
      relations, biocoenotic connections, and evolution. Ecological parasitology is a
      component of ecology, as the scientific study of the relation of living organisms
      with each other and their surroundings. In the present paper, critical analysis
      of the problems, main postulates, and terminology of the modern ecological
      parasitology is given.

PMID- 21874842
TI  - [Characteristics of the distribution of ticks Ixodes persulcatus and Ixodes
      pavlovskyi at the border between the forest and forest-steppe zones in the
      territory near Ob River].
AB  - Field investigations performed in 2009 and 2010 in the Novosibirskiy,
      Toguchinskiy, and Sovetskiy districts of Novosibirsk Province showed, that at
      present, Ixodes persulcatus, I. pavlovskyi (subspecies I. pavlovskyi occidentals
      Filippova et Panova, 1998), and Dermacentor reticulatus (Fabricius, 1794)
      permanently cohabitate in the woodland park of the Novosibirsk Akademgorodok, and
      I. pavlovskyi is the dominating species there. The highest abundance of I.
      pavlovskyi was recorded in pine forests subjected to intensive recreational load.
      At the same time, I. pavlovskyi was not found in the Novosibirskiy District and
      in the plane part of Toguchinskiy District, while the abundance of I. persulcatus
      is almost three times higher in the above mentioned territories, than in the
      Akademgorodok.

PMID- 21874843
TI  - [Structure of the component community of parasites of Gymnocephalus cernuus
      (Linnaeus, 1758) in different seasons].
AB  - In the conditions of middle stream of Vychegda River, the species diversity of
      parasite community associated with Gymnocephalus cernuus was found to be maximal
      in March and minimal in September. It is shown, that during a year the parasite
      community passes through the phases of development in December-March, completion
      in May-June, and destruction in July-September, which form the annual cycle of
      the community.

PMID- 21874844
TI  - [Life cycle of the trematode Echinochasmus spinosus Odhner, 1911
      (Echinostomatidae) in the natural conditions of Primorye].
AB  - Life cycle and developmental stages of the trematode Echinochasmus spinosus
      Odhner, 1911 are described. As it was established experimentally, in the
      conditions of Primorsky Krai circulation of the trematode involves first
      intermediate host, mollusk Parafossarulus spiridonovi, and the second one,
      freshwater fishes. Adult worms were reared in chicken.

PMID- 21874845
TI  - [Variability of myxospores in the myxosporidian genus Henneguya depending on host
      and geography in the transect "Khubsugul Lake (Mongolia)--Baikal Lake--Laptev Sea
      (Russia)"].
AB  - Analysis of variability and estimation of significance of the differences in
      morphometric parameters of spores have been carried out for three species of the
      genus Henneguya (Myxosporidia). Representatives of these species collected both
      in the same water body (but from different host species) and in geographically
      distant localities were compared. Thus, we compared samples of Henneguya
      zschokkei from different host species in Chivyrkui Bay of Baical Lake and in
      Laptev Sea, and also we compared samples of this species from Baikal Lake with
      those from Laptev Sea. Materials on Henneguya cerebralis from Baikal Lake were
      compared with those from Khubsugul Lake; samples of H. cutanea from one host
      species (Siberian dace) but from water bodies of different type (lake or river)
      were compared.

PMID- 21874846
TI  - [Helminthofauna of wild canids in Azerbaijan and ways of its formation].
AB  - The complete list of helminthes parasitizing canids in Azerbaijan is given; ways
      of formation of the canids' helminthofauna in Azerbaijan are reconstructed. As a
      result of our study, 42 helminth species were recorded; 25 of them parasitize
      jackals, 16 parasitize wolfs, and 39 species were found in foxes. The
      helminthofauna includes 5 species of Trematoda, 14 species of Cestoda, 1 species
      of Acanthocephala, and 22 species of Nematoda. By the life cycle, 32 species
      belong to biohelminthes and 10 species are geohelminthes.

PMID- 21874847
TI  - [Identification of mosquito-parasitic microsporidia, Amblyospora rugosa and
      Trichoctosporea pygopellita (Microsporidia: Amblysporidae), from Acanthocyclops
      venustus and Acanthocyclops reductus (Copepoda: Cyclopidae), based on small
      subunit rDNA analysis].
AB  - Identical small subunit rDNA sequences were obtained for microsporidia
      Amblyospora rugosa from blood-sucking mosquitoes larvae Ochlerotatus cantans, O.
      cataphylla and copepods Acanthocyclops venustus, as well as for Trichoctosporea
      pygopellita from mosquitoes larvae Ochlerotatus cyprius, O. excrucians and
      copepods Acanthocyclops reductus. The data on molecular phylogeny and ecological
      researches show that in Siberia mosquito-parasitic microsporidia of the genera
      Amblyospora and Trichoctosporea have complex life cycle involving likely
      intermediate hosts, Acanthocyclops copepods. Life cycle of parasites is
      synchronized with phenology of their hosts. The phylogenetic analyses shows, that
      genus Trichoctosporea should be transferred from the family Thelohaniidae to the
      family Amblyosporidae.

PMID- 21874848
TI  - [Unique characteristics of the energy metabolism in Microsporidia as a result of
      durational adaptation to the intracellular development].
AB  - Microsporidia is a large group of fungi-related unicellular eukaryotes with
      obligate intracellular lifestyle infecting a wide range of invertebrate and
      vertebrate hosts. Long adaptation of the parasites to intracellular development
      resulted in extraordinary minimization of their metabolic system. The paper
      summarizes the original results and literature data on the study of
      microsporidian carbohydrate and energy metabolism. On the basis of the material,
      it is concluded that minimization of microsporidian cell machinery was
      accompanied by the acquisition of a number of unique characteristics, which were
      not found in other eukaryotes.

PMID- 21874849
TI  - [Characteristic features of biodiversity in European ixodid ticks (Acari,
      Ixodidae) as vectors of diseses with natural foci].
AB  - The diapason of some biodiversity characteristics of ixodid ticks of the fauna of
      Europe and adjacent territories is analyzed. These characteristics include
      taxonomic and morphological diversity, the diversity of life cycles, host
      parasite relations, species ranges, and biotopic associations. The significance
      of different aspects of biodiversity of ixodid ticks as a prerequisite of
      interrelations with pathogens with natural foci is estimated.

PMID- 21874850
TI  - [Assemblages of bloodsucking mosquito larvae (Diptera: Culicidae) in water bodies
      of the northern Kulunda steppe].
AB  - The population structure of bloodsucking mosquito larvae in temporary and
      constant water bodies of the northern Kulunda steppe was investigated. The
      seasonal dynamics of the population density, the number of species in different
      types of reservoirs, and average density of each species are given. The
      productivity of water reservoirs in relation to mosquitoes of the family
      Culicidae is analyzed. The basic factors affecting the distribution of larvae of
      dominant species between different water bodies were revealed. The degree of
      correlation between the structure of bloodsucking mosquito larva assemblages and
      the type of the reservoir was established.

PMID- 21874851
TI  - [The influence of ecological factors on the formation of the parasite fauna of
      the common roach Rutilus rutilus Linnaeus (1758) in different periods of water
      abundance in Lake Sartlan (Southwestern Siberia)].
AB  - An analysis of the formation of the parasitofauna of the common roach under the
      influence of various biotic and abiotic environmental factors during three high
      water cycles observed in the last century is given. Periods of the formation of
      the enzooty are established.

PMID- 21874852
TI  - [Some results of the study of trematode fauna of the freshwater mollusc
      Melanopsis praemorsa (L.) from Azerbaijan water bodies. Report 3. New species of
      stylet cercaria].
AB  - The structure (illustrated by pictures) and differential diagnoses of 3 new
      closely related forms of stylet cercaria (Cercaria agstaphensis 8, Cercaria
      agstaphensis 21 and Cercaria agstaphensis 16) are given. Special attention was
      paid to the armament of the glandular apparatus, to the excretory and digestive
      systems, and to other taxonomically important structural peculiarities.

PMID- 21874853
TI  - [The fine structure of the cortical zone in the gregarine Bothriopsides histrio
      (Eugregarinida: Actinocephalidae)].
AB  - Attached and non-attached trophozoites of the septate gregarine Bothriopsides
      histrio were found in the intestine of the freshwater beetle Acilius sulcatus.
      Circular folds in the border between proto- and deutomerites and longitudinal
      striation, running along the entire body of the parasite, were revealed in an
      optical microscope. Our studies have demonstrated that circular folds, forming a
      specific collar, are formed of ecto- and endocytes. The longitudinal striation is
      represented by overdeveloped folds developed by the epicyte and the ectocite.
      Numerous typical epicite folds were observed over the entire cell surface.
      Additionally, the symbiosis between gregarine cells and bacteria was revealed.

PMID- 21874854
TI  - [Incidence of microsporidian infection of stem borers of the genus Ostrinia
      (Lepidoptera: Crambidae) in the Krasnodar Territory].
AB  - Infection of corn borers of the genus Ostrinia with microsporidia is found for
      the first time in Russia. Incidence rates of the last instar larvae of the second
      generation, sampled under natural conditions in the Krasnodar Territory, is
      ranged between 3.0 and 17.2%. When infection incidence rates have been compared
      between larvae, collected (a) on the western and eastern borders of the region
      and (b) on dicotyledonous (cocklebur, mugwort) and monocotyledonous plants
      (maize), no distinct differences were found. Infection rates were maximal in
      larvae of Ostrinia nubilalis when its population entered the depression phase,
      yet it did not differ significantly from the values of the previous years.
      Morphometric characters of the spores allows identifying the parasite species as
      Nosema pyrausta. These data demonstrate wide dispersal of microsporidia in the
      populations of stem borers on diverse forage plants within the boundaries of the
      Krasnodar Territory.

PMID- 21874855
TI  - [On the identification of the species Griphobilharzia amoena Platt, Blair, Purdie
      et Melville, 1991, a parasite of crocodiles in Australia].
AB  - The results of the study of typical specimens of the trematode G. amoena from
      blood vessels of the crocodile Crocodylus johnstoni in Australia are provided.
      The data obtained on the morphology of this parasite did not confirm the
      statement of Platt et al. (1991) that this species belongs to the family
      Schistosomatidae. Morphological data on G. amoena enable attributing it to the
      genus Vasotrema of the family Spirorchidae as a new species. In this connection,
      the monotypical genus Griphobilharzia (justified by Platt et al., 1991) becomes a
      synonym of the genus Vasotrema, while the subfamily Griphobilharziinae becomes a
      synonym of the subfamily Hapalotrematinae.

PMID- 21874856
TI  - [Peptides derived from the extracellular loop of receptors: structure, mechanisms
      of action and application in physiology and medicine].
AB  - One of the main tasks of the peptide strategy, a new direction in modern
      biochemistry and physiology, is the creation of selective and effective
      regulators of hormonal signaling systems on the basis of the peptides
      corresponding to functionally important regions of signal proteins. At the last
      years the greatest interest is connected with peptides, derivatives of the
      extracellular loops of receptors of the serpentine type. With these peptides the
      molecular basis of interaction between receptors and their ligands are studied,
      the new approaches for construction and testing of highly selective agonists and
      antagonists are developed, the etiology and pathogenesis of diseases of human and
      animals induced by autoimmune reactions to the extracellular loops of receptors
      are investigated. It is shown that peptides corresponding to the extracellular
      loops of the receptors and the specific antibodies to them are capable to
      regulate the activity of hormonal signaling systems in vitro and in vivo and can
      be considered as functional probes for studying of physiological functions in the
      norm and pathology. In the review the data obtained during the last years
      concerning the structures, functions, mechanisms of action and practical
      application ofpeptides, derivatives of the extracellular loops of serpentine type
      receptors, are summarized and analyzed. The prospective of their use in
      fundamental biology and practical medicine are discussed.

PMID- 21874857
TI  - [Changes of external respiration, brain circulation and the EEG in acute hypoxia
      in the subjects with different hypoxic resistance].
AB  - Two groups of individuals were distinguished in experiments with acute hypoxic
      action (respiration of oxygen-nitrogen mixture with 8 % oxygen content) - with
      low (LHR) and high (HHR) resistance to hypoxia. In subjects of the LR group,
      slowing down of the pulse rate and lowering of arterial pressure in the shoulder
      artery were observed on the 5th-10th minute of hypoxia. In the HHR subjects,
      primary growth of the pulse rate was followed by its stabilization; no
      significant changes of the arterial pressure were observed. In LHR subjects, in
      the first 5-10 min of the hypoxia, a significantly lower level of the blood
      oxygen saturation was observed in comparison to the HHR. In the LHR group, there
      was a higher increment of amplitude-frequency index of the rheoencephalogram in
      comparison to the HHR, indicating a higher increment of the cerebral blood flow.
      The slowing down of the pulse rate in the LHR subjects was accompanied with
      increasing cerebral pulse volume, so that in spite of the pulse rate slowing, the
      minute volume of cerebral circulation increased. In the LHR subjects, two-phased
      dynamics of the EEG was observed: in the first phase there was a slow growth of
      theta- and delta-band EEG spectral power, in the second phase (on the 5th-10th
      min of hypoxia), sharp (200-300 % of the background level) growth of the EEG
      spectral power in those bands was observed. In the HHR subjects, gradual growth
      of EEG spectral power occurred with relative stabilization on the 10th-12th min
      of hypoxia. Possible role of the stress in the collapse-like reaction during
      acute hypoxia is analysed, which might cause increase of the oxygen request of
      the brain, higher growth of cerebral blood flow and more pronounced lowering of
      functional activity of the brain in the LHR subjects.

PMID- 21874858
TI  - [Generation of Ponto-Geniculo-Occipital (PGO) waves as a possible reason of
      disturbances in visual perception in microsleep].
AB  - A hypothesis is put forward that one of the reasons for disturbances in visual
      perception during microsleep could be a spontaneous generation of Ponto-Geniculo
      Occipital (PGO) waves. If the PGO waves are generated in microsleep, they could
      propagate into different thalamic nuclei conveying visual infomation.
      Consequently, a propagation of visual infonnation from the retina (if the eyes
      are opened) to visual neocortical areas and to input basal ganglia nucleus,
      striatum could be impaired. According to previously proposed mechanism of visual
      processing, which includes visual attention, in absence of striatum activation by
      a visual stimulus, a disinhibition through the basal ganglia of superior
      colliculus that transfer visual information to dopaminergic structures becomes
      impossible. Due to absence of dopamine release in response to visual stimulus,
      the attention to this stimulus cannot start, and therefore its processing worsens
      in all visual cortical areas. The suggested hypothesis could be verified in
      experiments with artificially evoked microsleep using non-invasive methods for
      searching for the correlates of the PGO activity presence in the brain.

PMID- 21874859
TI  - [Sex steroids and monoamines in the system of neuroendocrine regulation of
      amygdala functions].
AB  - The aim of this review is a review of literature data, which characterize
      participation of monoamines brain systems and sex steroids in regulation
      (modulation) of the amygdalas' functions. Shown were characteristic
      noradrenergic, dopaminergic and serotoninergic systems and their representation
      in amygdala. Effect ofnoradrenaline, dopamine and serotonine on neurons of
      Amygdala was shown realized from appropriate cell receptors under modulated
      influence of sex steroids. Combined participation of monoamines and sex steroids
      occur in regulation of activity in cyclic centre of secretion and releasing of
      gonadotropins, constituted a base of forming adaptive (sexual, food and
      aggressive-defensive) behaviour, including stress reaction. The presented data
      could be used for understanding influence of gender factor on personality
      characteristics of humans, cognitive abilities and behavioural reactions, and
      also in application to development of optimal medicinal treatment of
      psychoneurological diseases.

PMID- 21874860
TI  - [Phenotropyl succinate as the means for correction of neuroimmune disturbances
      under conditions of informational-physical stress].
AB  - In Wistar rats, psycho-immune-modulating properties of phenotropyl succinate were
      studied under conditions of informational-physical stress. The effect
      ofphenotropyl succinate on the organism specific and unspecific resistance was
      studied. The data obtained indicate the phenotropyl succinate ability to release
      neuroimmune disturbances developing under conditions of informational-physical
      stress.

PMID- 21874861
TI  - [Somatosympathetic reflex in rats with various models of arterial hypertension].
AB  - Spontaneous and reflex activities of sympathetic nerve were compared in animals
      with arterial hypertension of different aetiology. Reflex discharges elicited by
      single-shock stimulation of afferent fibres were recorded. In acute experiences
      on anaesthetized rats with renovascular and spontaneous (SHR) model of arterial
      hypertension, electric basal and evoked activity (somatosympathetic reflex) in
      cervical sympathetic trunk were recorded. It is shown, that the spontaneous
      electric activity in sympathetic nerve of hypertensive rats is larger than
      spontaneous activity of normotensive control animals. The somatosympathetic
      reflex in hypertensive rats differs from that of control animals. In rats with
      renovascular model of hypertension, the reflex magnitude is reduced, and in the
      SHR the reflex is increased. Time characteristics of the reflex in hypertensive
      rats differed among them. It is suggested that functional activities of the brain
      stem in rats with different arterial hypertension model are unequal.

PMID- 21874862
TI  - [Contractile activity of pectoral channel and lymph nodes in rats under
      antiorthostatic influences].
AB  - It has been established that during short term body antiorthostatic positions
      lymphatic system carries out compensatory function, unloading the cardiovascular
      system from redundant exercise. The contractile activity of pectoral channel and
      lymphatic nodes in weightlessness (antiorthostatic influence) was studied. The
      functional role of neck lymph nodes is expressed by depositing of liquid during
      redistribution of the blood. The atony of neck lymph nodes as well as loss of
      pectoral channel and lymph nodes decrease the receptor sensitivity of vessels and
      nodes to the action of vasoactive substances.

PMID- 21874864
TI  - [Sexual specificity of change of pancreatic alpha-amylase activity in rats in
      cadmium intoxication].
AB  - It was shown that the activity of alpha-amylase in the pancreas tissue, intestine
      content and blood, as well as kinetic characteristics in different substratum
      concentration changed in males and females after unitary oral administration of
      chloride cadmium in the dose 5 mg/kg. It was revealed that, after a single
      administration of chloride cadmium, growth of the pancreas weight, contents of
      protein and activity of alpha-amylase in the pancreatic tissue increased with
      parallel reduction of activity of enzyme in the small intestine. In acute cadmium
      intoxication, functional reorganizations in the pancreas are identical to initial
      stages of carcinogenic shifts. Such shifts are more expressed in females in
      comparison with males, especially after the cadmium intoxication.

PMID- 21874863
TI  - [The effect of the coded amino acids on meso- and ectodermal tissue development
      in organotypic culture].
AB  - The effect of L-amino acids was investigated in organotypic tissue culture
      ofmesodermal tissue (spleen, myocardium) and ectodermal tissue (brain cortex) in
      mature rats. The low hydrophobic amino acids: asparagine, hystidine, serine,
      lysine, arginine and glutamine acid, induced the proliferation stimulation. The
      high hydrophobic amino acids had both the apoptose effect (spleen) and no effect
      at all (myocardium). The proliferation stimulation occurred in the ectodermal
      tissue under the effect of the high hydrophobic amino acids (asparagines acid,
      valine, threonine, methionine, leucine, isoleucine), whereas the low hydrophobic
      amino acids had no effect on the nervous tissue development. The combination of
      two amino acids one of which stimulated and another one inhibited the explant
      growth zone (or was not active in myocardium) lead to an increase of the
      stimulatory effect in meso- and ectodermal tissue. The amino acid modulated
      properties can be taken in consideration in synthesis of new regulatory peptides.

PMID- 21874867
TI  - [Molecular physiology of receptor mediated endocytosis and its role in overcoming
      multidrug resistance].
AB  - Receptor-mediated endocytosis plays important role in the selective uptake of
      proteins at the plasma membrane of eukaryotic cells. Endocytosis regulates many
      processes of cell signalling by controlling the number of functional receptors on
      the cell surface. The article reviews the mechanism of clathrin-dependent
      endocytosis and the possibility of using this phenomenon for the targeted
      delivery of drugs. Use of certain proteins as targeting component of drug
      delivery systems can significantly improve the selectivity of this drug, as well
      as to overcome the multidrug resistance of cells resulting from the activity of
      the ABC-transporters.

PMID- 21874865
TI  - [Immunosupressive effect of hypokinetic stress and sensitization of thymus to
      glucocorticoids].
AB  - 24-hour hypokinetic stress expressed in decrease of sensitivity of cellular and
      humoral immu nity to subsequent immunization with sheep erythrocytes was studied.
      The development of this phenomenon is associated with sensitization of lymphoid
      tissue to hypoplasia effect of glycocorticoid hormones. In introduction of
      glycocorticoid stress, the animals revealed a more pronounced depression of
      proliferative activity of thymocytes compared with non stressed animals.

PMID- 21874868
TI  - [Citrulline extracellular level in the nucleus accumbens during feeding
      behaviour].
AB  - In Sprague-Dawley rats, by means of in vivo microdialysis combined with HPLC
      analysis it was shown that a consumption of a novel food did not produce any
      changes in extracellular levels ofcitrulline (an NO-co-product) in the medial n.
      accumbens. In contrast, the rejection of the novel food caused a rise of the
      extracellular citrulline level in this brain area which can be completely
      prevented by intra-accumbal infusion of 0.5 mM 7-nitroindazple, a neuronal NO
      synthase inhibitor. The data obtained reveal for the first time that new food
      rejection (but not its consumption) is characterized by neuronal NO-synthase
      activation and, very likely, NO production in the medial nucleus accumbens.

PMID- 21874869
TI  - [Immunoreactivity of hypothalamic orexin neurons and expression level of
      preproorexin gene in them after lipopolysaccharide injection].
AB  - Hypothalamic orexin neurons are involved in the regulation of many physiological
      functions. The immunoreactivity of these neurons is shown to be altered after LPS
      injection. This phenomenon is characterized by definite time-space pattern and
      depends on dose of antigen applied. The expression level ofpreproorexin gene in
      rat hypothalamus was investigated in 2, 4 and 6 hours after injection of 25 and
      500 mkg/kg b. w. LPS. Both injections of higher and lower doses resulted in the
      increase of expression level of preproorexin gene after 2 hours that could
      suggest an enhancement of orexin synthesis in neurons. There were no significant
      changes in 4 and 6 hours after injection. The comparative analysis of the data
      obtained earlier with immunohistochemistry, and the data shown in the present
      study suggest the mechanisms of orexin neurons reaction to injection of LPS in
      different doses, i. e. the more considerable prevalence of orexin utilization
      over its synthesis in hypothalamic cells after injection of subseptic (500
      mkg/kg) dose of LPS.

PMID- 21874870
TI  - [Geometric imaging of coherent interrelationships of electroencephalogram alpha
      rhythm in dynamics of system effective human activity].
AB  - In subjects performing tasks quickly and precisely, geometric imaging of coherent
      connections among the EEG alpha-range potentials dynamically changed and turned
      out to be specific for each of the intended activity's stages. In the subjects
      performing tasks slowly and with errors, in different stages of effective human
      activity, a stability of the geometric image was observed. The revealed geometric
      imaging changing in different stages of effective activity seems to reflect a
      multi-level organization of the action results acceptor.

PMID- 21874871
TI  - [Effect of seizure activity on subunit composition of Ca2+/calmodulin-dependent
      protein kinase II in hippocampus of Krushinskii-Molodkina rats].
AB  - Using a Western blot method it was been shown that a aontent of beta-CaMKII
      subunit was decreased on 40 % in hippocampus of Krushinskii-Molodkina rats (rats,
      genetically prone to audiogenic seizures) in comparison with normal Wistar rats.
      Additionally, we have investigate the temporal modifications of alpha/beta-CaMKII
      subunits in dependent from number audiogenic fits (n = 1 or n = 5). The level of
      beta-CaMKII in hippocampus of naive KM rats and KM rats in 24 h after single
      audiogenic seizure was not different, but it was increased on 56 % through 72 h
      after convulsion fit. In contrast, both 5-fold seizures and 20-fold seizures
      (audiogenic kindling) reduced the beta-CaMKII levels in comparison with naive
      group. The levels of alpha-subunit protein kinase in hippocampus these
      experimental groups of animals were not different. We suggest a hypothesis, that
      modifications alpha/beta ratio can be viewed as specific "homeostatic mechanism",
      which provide for neuronal function in hippocampus, thereby changing the rules
      governing synaptic plasticity in dependence from preliminary neuronal activity.

PMID- 21874872
TI  - [Participation of beta2-integrins CD11b/CD18 and CD11c/CD18 in adhesion and
      migration of cells on fibrinogen].
AB  - The role of beta2-integrins CD11b/CD18 and CD 11c/CD 18 in adhesion and migration
      of leukocytes on fibrinogen was studied. The monoclonal antibodies against CD11b
      inhibited the spontaneous adhesion of monocytic THP-1 cells on fibrinogen,
      whereas antibodies to CD11c more effectively inhibited the adhesion stimulated by
      chemokine MCP-1. By the RNA-interference method the clones of THP-1 with reduced
      expression of CD11b and general beta2-subunit CD18 were obtained. MCP-I
      stimulated the adhesion to fibrinogen of THP-1 cells of wild-type and mutant
      cells with reduced expression of CD11b (THP-1-CD11b-low), but not of cells with
      low expression of CD18 (THP-1-CD18-low). THP-1-CD18-low cells were also
      characterized by the impaired chemotaxis in presence of MCP-1. The data obtained
      suggest that spontaneous cell adhesion to fibrinogen is mediated to a greater
      extent by CD11b/CD18 integrins, while chemokine-stimulated adhesion and migration
      is mostly dependent on CD11c/CD18 molecules.

PMID- 21874873
TI  - [Effect of nitric oxide/endothelin interaction on hyperoxic vasoconstruction].
AB  - The data obtained demonstrated that NO restrains ET-1 production and blunts ET-1
      mediated basal cerebrovascular tone. Local hyperoxygenation of the brain tissue
      decreases NO availability, supeoxide production, suppresses NO-mediated vascular
      tone and facilitates ET-1-mediated vasoconstriction.

PMID- 21874874
TI  - [The contractile function and electrical stability of the heart in different
      regimens of physical exercise].
AB  - Adaptation to moderate duration of physical loading causes identical levels of
      increase in threshold fibrillation of ventricles in wide range of their
      intensity. Rise of contractile heart function increases with prolonged adaptation
      regimen of heavy loading exercise. With hypokinesia and excessive physical load
      the sinking of threshold of fibrillation of ventricles occurs in lacking of
      alterations and with high contractile function of the heart respectively.

PMID- 21874875
TI  - [Signalling mechanisms of cardioprotective effect of hypothermic
      preconditioning].
AB  - The presented data demonstrate that hypothermic preconditioning prevents
      cardiomyocyte necrosis in response to ischemia-reperfusion, improves pump
      function of the heart during reperfusion period, and exerts an antiarrhythmic
      effect. The hypothermic preconditioning exerts more pronounced cardioprotective
      effect than ischemic preconditioning. The protective impact of hypothermic
      preconditioning depends upon 3-adrenergic receptor stimulation, an increase in
      cAMP levels, activation of protein kinase A and protein kinase C, AMP-activated
      protein kinase (AMPK) and mitochondrial permeability transition pore blocking.
      The hypothermic preconditioning had no effect on the phosphorylation of GSK-3J3
      (glycogen synthase kinase-3beta) and Akt-kinase. The reactive oxygen species end
      endogenous catecholamines are triggers or mediators of hypothermic
      preconditioning of heart.

PMID- 21874876
TI  - [Effects of histamine on contractile activity of lymphatic node capsules. The NO
      role].
AB  - Effects of histamine (10(-9)--5 x 10(-5) M) on the phase and tonic contractile
      activity of capsular smooth muscles of isolated bovine mesentery lymph node were
      investigated. Dual dose-depended effect of histamine was found. Low
      concentrations of histamine less than 10(-7) M caused a decrease of contractile
      activity, whereas higher concentrations of histamine (more than 5 x 10(-7) M)
      resulted in increase of the phase and tonic contractions. Both H1- and H2
      receptors of smooth muscle cells are involved in the response. Much of the
      relaxing histamine-induced response is produced by the stimulation of the
      endothelial cells. We believe that activating effect of histamine is due to the
      excitation of H1-receptors located on the membrane of myocytes, whereas its
      inhibitory effect occurs in two ways: 1) via excitation of H2-receptors located
      on the membrane of myocytes; 2) via stimulation of the NO production by the
      endothelial cells of lymph node sinus.

PMID- 21874877
TI  - [Service for Disaster Medicine of the Ministry of Defence of the Russian
      Federation at the present stage].
AB  - The basic documents of the history of service Disaster Medicine in the USSR and
      the Armed Forces of the country, employed in this branch of medical terminology,
      classification of emergency situations are presented. The problem of Disaster
      Medicine Service of the Ministry of Defence of the Russian Federation at the
      present stage, the levels of its operations and readiness, as well as the
      structure and objectives of the medical detachment for special purposes are
      considered. The involvement of service in peacekeeping operations and medical
      support of local armed conflicts are assessed.

PMID- 21874878
TI  - [Analysis of recruits and doctors satisfaction in Orenburg region organization of
      medical support training of citizens for military service].
AB  - In the article results of questioning on studying of opinion of 1023 recruits at
      the age from 18 till 26 years and 323 doctors--the experts working as a part of
      the invocatory commissions of municipal unions of the Orenburg region about the
      organization of medical maintenance of preparation of citizens to military
      service, including preventive medical inspections, medical-improving actions,
      supervision of young men and physical examination in the invocatory commissions
      where the validity category to military service is defined are presented.

PMID- 21874879
TI  - [The impact of health personnel at the cohesion of military units].
AB  - It is shown that in military units sociometric status of troops largely
      determined by the frequency of diseases in the following classes of diseases:
      mental and behavioral disorders (grade 7), diseases of the eye (grade 7),
      diseases of the ear and mastoid process (grade 8) and diseases of the digestive
      system (grade 11). Therefore, prevention efforts on these types of diseases will
      help to create cohesive military units, but it rebuet presence in the military
      link of the medical service of specialists.

PMID- 21874880
TI  - [Tracheostomy in the process of prolonged artificial pulmonary ventilation in
      patients with polytrauma].
AB  - One of modern tendencies of carrying out long ALV of patients with polytrauma is
      application of "early" tracheostomy. Thus optimum terms of early tracheostomy are
      defined indistinctly and vary from 2 to 10 days from beginning of ALV. It is
      established that at predicted long ALV of patients with polytrauma optimum terms
      of tracheostomy performance is the second period of traumatic illness (12-48
      hours from the moment of getting trauma). Tracheostomy, executed for patients
      with polytrauma for the purpose of maintenance long AL V in early terms, promotes
      improvement of gases diffusion, microcirculation in lungs, improvement of system
      of external breath as a whole and it is accompanied by decrease in frequency of
      development life danger infectious pulmonary complications and lethality
      reduction.

PMID- 21874881
TI  - [The importance of vascular surgery and path morphology in therapy of
      parasympathetic chemodectomas].
AB  - Was closely studied the material of 28 extracted chemodectomas. On the basis of
      modern methods of morphological investigation (histological, electronic
      microscopic methods) were ascertained criterions of their malignant nature; for
      the first time was described the phenomenon of vessels overgrowing.

PMID- 21874882
TI  - [Principles of treatment of early stage glaucoma: surgery vs. therapy (review of
      literature)].
AB  - Swift development of ophthalmopharmacology in last years has led to loss of
      starting positions surgery in glaucoma treatment, especially in early stage.
      Medical therapy is considered safer and not less effective in spite of problems
      of compliance, intolerance to hypotensive drugs in some patients with ocular
      surface diseases and less significant reduction of baseline intraocular pressure.
      There are many glaucoma guidelines refer to this data which led to significant
      decrease of proportions of surgery. Whether such an approach is applicable in all
      cases?

PMID- 21874883
TI  - [Prevention of recurrence of benign ovarian tumors in women of reproductive age
      after urgent operations].
AB  - A comprehensive analysis of the survey and emergency surgical treatment 152
      troops of women of reproductive age for benign tumors and tumor-like formations
      of ovaries, who applied to gynecological Otdleneiya Garrison Military Hospitals
      in the Far East region from 1999 to 2009 is made. For patients characterized by
      the predominance of ovarian tumor formation in 65.1% of benign ovarian tumors
      (34.9%). In patients of reproductive age undergoing surgery for benign ovarian
      tumors implementation of the proposed rehabilitation system allows you to restore
      reproductive function in 37.5% of cases for 1 year after surgery and recurrence
      of ovarian neoplasms during the observation period of 2 years.

PMID- 21874884
TI  - [Prospects for reducing the incidence of military air-borne infections which are
      not controllable by means of vaccination].
AB  - Examines the state of immunization by means of uncontrolled disease vaccine
      (influenza, SARS, pneumonia, streptococcal and meningococcal infections). They
      cause disease in both children and adolescents, as well as in organized
      collectives of adults, especially among conscripts. Calendars vaccination of the
      population and soldiers regulate immunization risk of epidemic indications
      against influenza, and partly against meningococcal infection; gradually
      introduced to the troops Immunoprophylaxis of pneumococcal pneumonia. Not solved
      the problem of immunization of adenovirus and streptococcal infections in
      military personnel. Discussed ways to improve your calendar vaccination of
      military personnel on extended epidemic indications against the mentioned
      diseases.

PMID- 21874885
TI  - [The classification of the bailout for the professional health of flight
      personnel].
AB  - The paper considers existing approaches to the classification of outcomes of
      emergency egress the aircraft. The existing classification of time-related
      manifestations of the outcome of the bailout supplemented with clause immediate
      consequences bailout. The analysis of the effects of aircraft emergency escape
      for the pilot's health, special attention is paid to long-term consequences,
      their impact on professional practice.

PMID- 21874886
TI  - [Advanced of progressive design approaches to produce Medical Packaging Boxes for
      modern functional complete sets of medical property].
AB  - New types of medical packaging boxes represent collapsible products based on
      solid metal pieces and flat polymeric panels with stiffening ribs. They allow to
      implement the advanced methods of medical property storage and correspond to the
      standards of modern container-transporting system. They have high repairability
      level and insignificant own weight. The main elements and junctions can be
      interchanged as well as the whole box can be transformed into field medical
      furniture.

PMID- 21874887
TI  - [Sanitary and chemical protection during the Great Patriotic War].
AB  - During the Great Patriotic War (1941-1945) there was a real danger of use by
      German armies of the chemical weapon against staff of Red Army. However German
      command didn't risked to go on conducting large-scale chemical war against the
      USSR that rescued from painful death millions person. A principal cause of this
      decision was well organized and technically provided system of antigas protection
      in Red Army, including precisely organized actions of sanitary-chemical
      protection, qualitative preparation of military doctors on these questions and
      presence at them effective antidotes and other means of treatment of injuries by
      fighting poison gases.

PMID- 21874888
TI  - [From the history of the Kirov Evacuation Hospital N 1322 during the war].
AB  - During the Great Patriotic War in Kirov Red Army soldiers provided specialized
      psychiatric care. 24 June 1942 on the basis of evacohospital N 1322 was organized
      by the psychiatric ward. This department carries out all necessary psychiatric
      care until November 1945.

PMID- 21874889
TI  - [Origins of the coat, appearance of physicians of the Russian fleet in the first
      third of XVIII century].
AB  - The article is devoted to the reconstruction of medical uniforms Russian navy
      first third of the 18th century. It can be assumed that doctors were in varying
      degrees, the senior officer's dress, but of course without the braid, although
      there are exceptions, which related to doctors willing to go to a more senior
      hypostasis. A number of documents of different structures gives rise to speak
      with a high probability that the doctors of different ranks, serving in the
      Marine units that had shaped dress that is largely consistent with their position
      in the hierarchy of ranks and received in the near future, its development.

PMID- 21874890
TI  - Conservative treatment of periodontal recessions with class v-defects using
      gingiva-shaded composite--a systematic treatment concept.
AB  - Periodontal recessions can cause aesthetic and functional problems, especially in
      the anterior region or when combined with exposed crown margins. A combination of
      periodontal disease, recession with exposed root surface, hard-tissue defects and
      age emphasizes the need for treating these defects. If crown margins are exposed
      and surgical treatment is not possible, aesthetics and function can only be
      improved by replacement of the restoration. The restorative treatment option with
      a gingiva-shaded composite is especially valuable for dental fear patients or
      older patients with general or local risk factors, surgical contra-indications or
      Class III and IV recessions with questionable prognosis of surgery. The step-by
      step-approach described in this article is an alternative, minimal-invasive
      treatment concept for cervical lesions in combination with all kinds of
      periodontal recessions, that is especially suitable for wedge-shaped defects next
      to exposed crown margins.

PMID- 21874891
TI  - Defective dental restorations: to repair or not to repair? Part 1: direct
      composite restorations.
AB  - The presentation of patients with failing dental restorations that exhibit minor
      defects is a common clinical situation in everyday dental practice. The repair of
      such restorations, rather than replacement, is increasingly considered to be a
      viable alternative to the replacement of the defective restoration. This first of
      two papers considers indications and techniques for the repair of defective
      direct composite restorations. It is possible that some dental practitioners are
      unaware of the option of repair rather than replacement of composite
      restorations. This article provides an overview of contemporary knowledge and
      understanding of restoration repair in the clinical management of defective
      composite restorations.

PMID- 21874892
TI  - Chronic ulcerative stomatitis: a distinct clinical entity?
AB  - Chronic ulcerative stomatitis (CUS) is a mucocutaneous disorder which is
      characterised by persistent oral mucosal ulceration. The clinical appearance is
      often reminiscent of oral lichen planus (OLP) leading to erroneous diagnoses. The
      immune mediated inhibition of the CUS protein (CUSP) is implicated in the
      pathogenesis of CUS. CUSP acts as an anti-apoptotic protein and when its action
      is prevented it may result in significant epithelial injury. The objective or
      this article is to present the first documented case of CUS in South Africa, with
      relevant reference to current international literature. CUS should be considered
      in patients previously diagnosed with OLP but who are unresponsive to
      glucocorticosteroid therapy. The condition can be successfully managed using
      hydroxychloroquine.

PMID- 21874893
TI  - Methamphetamine abuse: a review of the literature and case report in a young
      male.
AB  - Methamphethamine (TIK) is a highly addictive drug that acts as a stimulant for
      the central nervous system. It increases wakefulness and physical activity and
      can cause cardiac dysrhythmias, hypertension, hallucinations and violent
      behavior. Dental patients abusing methamphetamine often present with poor oral
      hygiene, xerostomia, rampant caries ("meth mouth") and excessive tooth wear.
      Management of these conditions is often challenging. A 24-year-old Caucasian man
      presented with severe dental pain, halitosis and self-reported poor dental
      appearance. A comprehensive examination including his medical history, panoramic
      radiographs and extra- and intraoral examination revealed 19 carious and erosive
      lesions. He reported using methamphetamine for eleven years and had not
      experienced much caries prior to using the drug. The patient's medical and dental
      histories along with radiographic and clinical findings led to a diagnosis of
      "meth mouth." Although various dental treatment options were offered to the
      patient, he opted for extraction of the most painful teeth in the left lower
      madibular quadrant and has yet to return for further treatment. This literature
      review and clinical case description of the oral manifestations of "meth mouth"
      is intended to alert dental practitioners to recognize and manage patients who
      are abusing methamphetamines. They should also be aware that these patients are
      often unreliable at following prevention advice as well as keeping follow-up
      appointments.

PMID- 21874894
TI  - Whitening efficacy of three over-the-counter oral rinses.
AB  - AIM: The aim of the study was to determine the whitening efficacy of three
      different oral rinses. MATERIALS AND METHODS: Eighty extracted teeth were
      randomly divided into four groups, cleaned with a slow-speed handpiece with
      pumice and placed in a staining broth for 14 days. Measurements of tooth shades
      were measured with a spectrophotometer. Three groups (20 each) were then exposed
      to Colgate Plax Whitening Blancheur (A), White Glo 2 in 1 (B) and Plus White (C)
      for 21 days for 2 minutes a day and in between stored in artificial saliva. The
      other group acted as a control and was only stored in the artificial saliva.
      RESULTS: The Kruskal-Wallis and Tukey-Kramer analysis showed no statistical
      significant differences (on a 5% basis) for the differences between base-line and
      after treatment (21 days) for deltaL*, deltaa*, deltab* and deltaE*ab median
      values amongst the control, Colgate Plax Whitening Blancheur, White Glo 2 in 1,
      and Plus White. CONCLUSION: None of the 3 commercially available oral rinses
      resulted in any significant bleaching effect on the teeth over a 21 day treatment
      period.

PMID- 21874895
TI  - Centric occlusion and all that other stuff.

PMID- 21874896
TI  - General practitioner's radiology case 91. Dilaceration affecting the roots of
      teeth.

PMID- 21874897
TI  - How will the new Consumer Protection Act (CPA) affect your dental practice?

PMID- 21874898
TI  - Dental ethics case 10: advertising your field of practice after completing CPD
      course.

PMID- 21874899
TI  - [Inhibition of HIV virus-like particles production by BST-2].
AB  - Recently, BST-2 has been identified as an effective cellular factor that prevents
      the release of human immunodeficiency virus type 1 and other enveloped viruses by
      tethering virus particles to the cell surface. Here, we showed that the
      production of HIV-1 virus-like particles was markedly inhibited by BST-2. Both
      the transient and stable expressing of BST-2 had the same function and Vpu
      rescued the release of HIV-1 VLP in the presence of human BST-2. Consistent with
      a direct tethering mechanism, we confirmed that proteolysis releases restricted
      virions and further showed that this removed the ectodomain of BST-2 from the
      cell surface.

PMID- 21874900
TI  - [Study of biological characteristics of the IVpi-189 virus derived from
      persistent influenza A virus-infected cell line].
AB  - To investigate biological characteristics of the IVpi-189 progeny virus derived
      from the culture of influenza A virus as a live-attenuated vaccine candidate.
      Persistent infection of a cultured cell line with influenza A virus (MDCK-IVpi)
      was established by incubating continuously influenza virus-infected cells at a
      lower temperature. The infectious progeny virus derived from MDCK-IVpi cells at
      the 189rd subculture was designated as the IVpi-189 strain of influenza virus.
      The cytopathic effect induced by IVpi-189 virus was observed under different
      temperature conditions. The production of infectious progeny virus was examined
      at 38 and 32 degrees C by plaque titration of cell-associated and released virus.
      IVpi-189 virus showed cytopathic effect as strong as that of IVwt in infected
      cell line of MDCK at 32 degrees C. However, when culture temperature was raised
      to 38 degrees C, the cytopathic effect induced by IVpi-189 virus was delayed and
      less pronounced. Virus growth in IVpi-189 virus-infected cells at 38 degrees C
      was significantly reduced as compared with that of IVwt virus, although both
      viruses yielded nearly equivalent high titers of cell-associated and released
      virus at 32 degrees C. The reasons of the decreased proliferative ability of IVpi
      189 virus at high culture temperature were unrelated with virus inactivation or
      the release of progeny virus, but associated with the decreased replication of
      infectious progeny virus in the infected cells. IVpi-189 virus derived from MDCK
      cells infected persistently with influenza A virus showed biological
      characteristics as a potential live-attenuated vaccine candidate.

PMID- 21874901
TI  - [Development of a GeXP based multiplex RT-PCR assay for simultaneous
      differentiation of nine human hand food mouth disease pathogens].
AB  - A multiplex RT-PCR assay based on GeXP system was developed in order to detect
      simultaneously human enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) and
      other coxsackieviruses (CVA4, 5, 9 and 10, CVB1, 3 and 5). Enterovirus detection
      was performed with a mixture of 12 pairs of oligonucleotide primers including one
      pair of published primers for amplifying all known pan-enterovirus genomes and
      eleven primer pairs specific for detection of the VP1 genes of EV71, C A16, CVA4,
      CVA5, CVA9, CVA10, CVB1, CVB3 and CVB5, respectively. The specificity of
      multiplex RT-PCR system was examined using enterovirus cell cultures and positive
      strains identified previously from hand-foot-and-mouth disease (HFMD) patients.
      Serial dilution of titrated EV71 and C A16 cell cultures and in vitro
      transcripted RNA of enterovirus VP1 regions were used to detect the sensitivity
      of the multiplex RT-PCR system. The limit of detection for this multiplex RT-PCR
      system was 10(0.5) TCID50/microL for EV71 and C A16 cell cultures and 1000 copies
      for in vitro transcripted RNA of nine viruses per assay. This multiplex RT-PCR
      assay is a rapid, sensitive and specific assay for the diagnosis of common
      enterovirus infection in cases of HFMD outbreak and is also potentially useful
      for molecular epidemiological investigation.

PMID- 21874902
TI  - [Genetic characterization of poliovirus isolates from environmental sewage
      surveillance in Shandong, 2010].
AB  - To investigate the genetic characteristics of poliovirus isolates from
      environmental sewage surveillance in Shandong province, we collected sewage
      samples in Jinan and Linyi City. Serotyping and VP1/ 3D sequencing were performed
      on polioviruses isolated from the concentrated sewage samples, and VP1 mutation
      and recombination were analyzed. Thirty-two of sewage samples were collected, and
      polioviruses were detected in 10 of the samples with a positive rate of 31.3%.
      Eighteen Sabin strains were isolated including three type 1, nine type 2, and six
      type 3 polioviruses, and the number of nucleotide substitutions in VP1 coding
      region varied from 0 to 4. Recombination was found in three Sabin 2 and four
      Sabin 3 polioviruses. Analysis of neurovirulence sites of VP1 revealed that one
      Sabin 1 vaccine strain had a nucleotide change of A to G at nt 2749, one Sabin 2
      strain had a nucleotide change of A to G at nt 2908, three Sabin 2 strains had a
      nucleotide change of U to C at nt 2909, and all six Sabin 3 strains had a
      nucleotide change of C to U at nt 2493. Poliovirus vaccine strains could be
      isolated from environmental sewage with a high rate of gene recombination and
      back mutation of neuvirulence-associated sites. None of wild-type poliovirus or
      vaccine-derived poliovirus was detected.

PMID- 21874903
TI  - [Molecular typing of enteroviruses from healthy children in the border areas of
      Yunnan Province and Myanmar and the genetic characteristics of ECHO7 and ECHO13
      in 2009].
AB  - To explore the enteroviruses surveillance among healthy children under 15 years
      old in the border areas of Yunnan Province and Myanmar in 2009. The stool samples
      were collected from the healthy children under 15 years old who came from the
      border areas of Myanmar and Yunnan Province, virus isolation and sequencing were
      conducted for all the 271 samples. 6 strains of polioviruses (PVs) were detected
      from 271 stools with an isolation rate of 2.8%, which belonged to vaccine strains
      and 24 non-polioviruses (NPVs) were detected with an isolation rate of 8.9%. 24
      NPVs belonged to human enterovirus group B (HEV-B) with 6 serotypes, HEV-A, HEV-C
      and HEV-D viruses were not isolated. Among them, 13 NPVs were E7 (54.17%) and 5
      NPVs were E13 (20.83%). Our results showed that the enterovirus carrying rate in
      the border areas of Yunnan province was higher than the rate of routine acute
      flaccid paralysis (AFP) detection system. The HEV-B viruses were the only
      enteroviruses isolated. The phylogenetical analysis showed that Echovirus 7(E7)
      and 13 (E13) exhibited genetic polymorphism.

PMID- 21874904
TI  - [Establishment of SeMNPV persistent infection in Spotoptera exigua cells].
AB  - Persistent baculovirus infection is observed frequently in insect populations.
      Persistent infection can be transformed to a replicative and infective state
      caused by stress factors and plays an important role in regulating the size of
      insect population and in epizoology of baculoviruses. The aim of this study is to
      establish a persistently baculovirus-infected cell system to explore the
      molecular mechanisms of baculoviral persistence. Spodoptera exigua
      nucleopolyhedrovirus (SeMNPV) was serially undiluted passaged in Se301 cells to
      reduce virulence. Upon infection of Se301 cells with the SeMNPV up to passage 8,
      a few cells survived even if most of cells died due to virus infection. The
      surviving cells were passaged and designated as P8-Se301 cell strain. P8-Se301
      cells had a population doubling time of 58-65 hours and grew slower than Se301
      cells. Light microscopy and electron microscopy observation showed symptom of
      baculovirus infection, such as virogenic stroma, viral particles and occlusion
      bodies, in some of P8-Se301 cells. End-point dilution assay and infectious center
      assay showed that 4.14% +/- 0.99% cells continually released infectious progeny
      virus which replicated slower than SeMNPV in Se301 cells. The result indicated
      that P8-Se301 cells show a typical character trait of baculovirus persistent
      infection.

PMID- 21874905
TI  - [Expression and identification of sigmaC gene of avian reovirus by baculovirus
      expression system].
AB  - Recombinant baculovirus containing sigmaC gene of Avian reovirus was constructed
      using Bac-To-Bac Baculovirus expression system, and recombinant sigmaC protein
      was expressed by infecting the sf9 cell with recombinant baculovirus. Firstly,
      sigmaC gene of Avian reovirus was cloned and inserted into donor plasmid
      pFastBacHTA to obtain recombinant donor plasmid pFsigmaC. Plasmid pFsigmaC was
      transformed into E. coli DH10Bac for integration into bacmid vector and the
      recombinant bacmid plasmid BacmidsigmaC was obtained. Recombinant baculovirus
      rBacsigmaC was obtained by transfection of the sf9 cells with BacmidsigmaC.
      Western blot and indirect immunofluorescence assay (IFA) were carried and the
      results showed that the recombinant sigmaC protein with 37 kDa molecular weight
      was expressed successfully.

PMID- 21874906
TI  - [Molecular properties of grass carp reovirus in southern China and establishment
      of a duplex PCR detection method].
AB  - A strain of grass carp reovirus was isolated from sick grass carp with symptoms
      of haemorrhage in Guangdong province in 2009. The strain was tentatively named as
      GCRV-GD108 because it was isolated from grass carp and possessed 11 segments of
      dsRNA. Complete genome sequence analysis showed that significant differences
      existed between GCRV-GD108 and GCRV, as well as other known species of
      aquareovirus. In this study, molecular characteristics of diseased grass carp
      collected from different farms in Guangdong, Fujian and Hunan provinces were
      assayed. Based on the sequences of the 11 segments of GCRV-GD108, PCR primers
      corresponding to each of the segments were designed and synthesized. Total RNA of
      the diseased fish was extracted and used as templates of RT-PCR reaction.
      Specific amplification bands were obtained from all of the samples whereas no
      band was produced from GCRV standard strain. While using the primers specific to
      GCRV produced specific band in GCRV standard strain rather than in these
      collected samples. Sequencing of the amplification products showed that these
      samples displayed high similarities with each other (95.2%-99.4%), and they also
      shared high sequence similarities with that of GCRV-GD108 (95.0%-99.8%),
      suggesting that these samples shared similar molecular characteristics with those
      of GCRV-GD108, and were quite different from GCRV as well as the known species of
      genus aquareovirus. The results indicated that there are different molecular
      types of reovirus existed in the pond-cultured grass carp in China, and GCRV
      GD108 is a representative strain in southern China, therefore great attention
      should be paid in order to control the disease efficiently, especially in vaccine
      preparation. Two pairs of primers were chosen to establish a duplex PCR assay
      method by combining each pair of the primers specific to GCRV-GD108 with the GCRV
      primer pair respectively. The duplex PCR assay method will enable the
      identification of GCRV-GD108 or GCRV by only a single PCR reaction.

PMID- 21874907
TI  - [Co-occlusion of foreign protein into polyhedra with BmNPV polyhedrin].
AB  - In order to make clear the packing mechanism of the BmNPV polyhedra, a polyhedrin
      gene negative recombinant baculovirus, vBmBac(polh-)-5B-EGFP, expressing EGFP was
      constructed, and used to infect BmN cells jointly with wild-type BmNPV.
      Fluorescent microscopic observation demonstrated that EGFP and polyhedrin were
      expressed simultaneously, and the EGFP expression and polyhedra formation
      occurred in most of the jointly infected cells. Analysis of the purified
      polyhedra from jointly infected BmN cells showed that the foreign proteins were
      present in the polyhedra. The results indicated that BmNPV polyhedrin could
      incorporate proteins other than viral proteins into the polyhedra. It implies
      that a nonspecific recognition mechanism exists in the embedment of BmNPV
      polyhedra.

PMID- 21874908
TI  - [Chikungunya fever].

PMID- 21874909
TI  - [Progess in the development of VLPs vaccine].

PMID- 21874910
TI  - [Advances in virus modification with macromolecule].

PMID- 21874911
TI  - [Progress in the genome and viral proteins of yellow fever virus].

PMID- 21874912
TI  - [Mitochondria and innate immunity].

PMID- 21874913
TI  - [The development of influenza virus-like particle vaccines].

PMID- 21874914
TI  - Move to accountable care puts case managers in the spotlight.
AB  - Medicare accountable care organizations (ACOs) offer opportunities and challenges
      for case managers as providers focus on coordinating care throughout the
      continuum. Pressure for accountability and managing resources efficiently are
      increasing. The Centers for Medicare and Medicaid Services (CMS) and other payers
      are beginning to base reimbursement on quality. ACOs change the payment system by
      bundling reimbursement across settings of care.

PMID- 21874915
TI  - ACOs: just part of the bigger picture.

PMID- 21874916
TI  - CM process redesign focused on level of care.
AB  - Cheyenne (WY) Regional Medical Center is redesigning its case management program
      to address level-of-care issues after the recovery audit contractor's
      determination that a number of inpatient stays should have been billed as
      observation. The hospital determined a lot of variation in level-of-care orders
      from attending physicians. A multidisciplinary team created a guide for
      physicians to use in determining level of care. Physicians are required to use a
      level of care form in order to admit a patient.

PMID- 21874917
TI  - Program for uninsured saves $4.56 million.
AB  - Memorial Hermann Healthcare System's program that provides support for uninsured
      patients saved the Houston hospital $4.56 million over an 18-month period. Social
      workers receive notification when a patient flagged for the program comes to the
      emergency department. They educate patients about the need to see primary care
      providers instead of coming to the emergency department and match them with
      clinics that provide free or reduced cost care. They work to overcome barriers to
      care such as providing assistance with transportation or medication. Chronically
      ill patients are eligible for coaching from an RN case manager.

PMID- 21874918
TI  - Case management insider. Roles and functions of ED case manager.

PMID- 21874919
TI  - Case management insider. Social work in the emergency department.

PMID- 21874920
TI  - Hospital organization, insurer collaborate.
AB  - Blue Cross and Blue Shield of Illinois and the Illinois Hospital Association are
      leveraging their resources and collaborating on a quality improvement initiative
      designed to reduce the rates of hospital readmissions. The insurer has committed
      up to $1 million a year to help hospitals acquire the resources and staff to
      implement readmission reduction programs. The program promotes specific case
      management and discharge planning interventions designed to keep patients from
      being rehospitalized. Hospitals may choose to participate in any or all of an
      array of initiatives.

PMID- 21874921
TI  - Hospitals beef up efforts to reduce readmission.

PMID- 21874922
TI  - Slash door-to-doc time, boost patient approval.
AB  - With patient satisfaction in the single digits and door-to-doc times unacceptably
      high, the ED at Sumner Regional Medical Center in Gallatin, TN, initiated a staff
      driven improvement effort aimed at weeding out inefficiencies. By putting the
      triage process under close scrutiny, staff members were able to eliminate dozens
      of tasks from the triage process, thereby slashing wait times. ED patient
      satisfaction has gone from the 5th percentile to the 98th percentile in just four
      months. A 44-step triage process has been streamlined into four steps, and
      average door-to-doc times have decreased from 67 minutes to 18 minutes. Further
      improvements are anticipated when ED administrators put staff scheduling under
      the same scrutiny.

PMID- 21874923
TI  - Independent association of the variant rs1333049 at the 9p21 locus and coronary
      heart disease.
AB  - INTRODUCTION: Recent genome-wide association studies have identified single
      nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary
      artery disease (CAD). Among them, the SNP rs1333049 has demonstrated a consistent
      association with CAD, which has been successfully replicated in several
      populations. AIM: To investigate whether the SNP rs1333049 located on the 9p21
      chromosome is an independent risk factor for CAD in a Portuguese population.
      METHODS: We performed a case-control study which included 1406 individuals, 723
      consecutive coronary patients (mean age 53.71 +/- 8.9 years, 79.9% male and 683
      controls without coronary disease (mean age 53.3 +/- 10.5 years, 73.9% male).
      Cases and controls were selected so as not to be significantly different in terms
      of gender and age. We studied the SNP rs1333049 at the 9p21 locus in all
      individuals, using standard PCR combined with the TaqMan technique (Applied
      Biosystems). The allelic and genotype distribution (C/G), odds ratios and
      corresponding confidence intervals for CAD risk were determined. A forward Wald
      logistic regression analysis model was constructed, adjusted for age, gender,
      conventional risk factors, biochemical markers and the genotypes under study, in
      order to determine which variables were linked significantly and independently
      with CAD. RESULTS: The C allele was found in 60% of the CAD patients and 53% of
      the controls, with OR = 1.33; p = 0.0002. The CC genotype appeared in 35.7% of
      CAD patients, with OR = 1.34, p = 0.010. The heterozygous CG genotype was present
      in 48.1% of the CAD patients and 47% of the controls, and did not present
      vascular risk (OR = 1.05, p = 0.670). After logistic regression analysis, the CC
      genotype remained in the equation with OR = 1.7; p = 0.018 and CG with OR = 1.5,
      p = 0.048. CONCLUSION: In the present study we replicated the coronary risk
      linked to the recently discovered variant rs1333049 on the 9p21 chromosome in a
      Portuguese population. Although the mechanism underlying the risk is still
      unknown, the robustness of this risk allele in risk stratification for CAD has
      been consistent, even in very different populations. The presence of the CC or CG
      genotype may thus prove to be useful for predicting the risk of developing CAD in
      the Portuguese population.

PMID- 21874924
TI  - The search for genetic predictors of coronary artery disease: the saga continues.

PMID- 21874925
TI  - Delayed lead perforation: a rare cause of pacemaker dysfunction.
AB  - A 65-year-old woman with a dual-chamber pacemaker implanted in 2006 for
      symptomatic carotid sinus hypersensitivity was incidentally found to have loss of
      ventricular capture on routine pacemaker interrogation. A chest X-ray raised the
      suspicion of perforation and migration of the right ventricular lead, confirmed
      by three-dimensional echocardiogram and CT scan. On the basis of this case, we
      review myocardial lead perforation, including predisposing factors,
      pathophysiological mechanisms, diagnostic approach and therapeutic options.

PMID- 21874926
TI  - Acute bivalvular left-sided methicillin-resistant Staphylococcus aureus
      endocarditis with cardiac, cerebral, renal and septic complications.
AB  - Infective endocarditis (IE) is now rare in developed countries, but its
      prevalence is higher in elderly patients with prosthetic valves, diabetes, renal
      impairment, or heart failure. An increase in health-care associated IE (HCAIE)
      has been observed due to invasive maneuvers (30% of cases). Methicillin-resistant
      Staphylococcus aureus (MRSA) and Enterococcus are the most common agents in
      HCAIE, causing high mortality and morbidity. We review complications of IE and
      its therapy, based on a patient with acute bivalvular left-sided MRSA IE and a
      prosthetic aortic valve, aggravated by congestive heart failure, stroke, acute
      immune complex glomerulonephritis, Candida parapsilosis fungemia and death
      probably due to Serratia marcescens sepsis. The HCAIE was assumed to be related
      to three temporally associated in-hospital interventions considered as possible
      initial etiological mechanisms: overcrowding in the hospital environment, iv
      quinolone therapy and red blood cell transfusion. Later in the clinical course,
      C. parapsilosis and S. marcescens septicemia were considered to be possible
      secondary etiological mechanisms of HCAIE.

PMID- 21874927
TI  - Giant left atrial thrombus: an unexpected finding.
AB  - The incidence of left atrial thrombi is higher in patients with mitral valve
      stenosis. Its presence and location have important implications in deciding on
      the therapeutic approach, particularly the need for valve repair. We describe the
      case of a 63-year-old patient, with asymptomatic moderate mitral stenosis,
      hospitalized due to community-acquired pneumonia, in whom investigation to
      exclude pulmonary thromboembolism revealed a giant left atrial thrombus, which
      required urgent surgery.

PMID- 21874928
TI  - Three-dimensional transesophageal echocardiography in percutaneous left atrial
      appendage closure.

PMID- 21874929
TI  - Subclavian steal syndrome in a coronary patient.

PMID- 21874930
TI  - Influence of five home whitening gels and a remineralizing gel on the enamel and
      dentin ultrastructure and hardness.
AB  - PURPOSE: To investigate the influence of calcium phosphate enhanced home
      whitening agents on human enamel and dentin surface microhardness and
      ultramorphology. METHODS: Five intact molars crowns were used for ultrastructural
      analysis and five for microhardness test. Each resulting coronal structure was
      cut in slices. After measuring baseline Knoop Hardness Number (KHN) of the enamel
      and dentin, the slices were divided into six experimental groups and one control
      (n= 5). G1= 15% carbamide peroxide (CP); G2= 16% CP; G3= Ca and PO4
      (remineralizing agent); G4= 16% CP with Ca and PO4; G5= 7.5% hydrogen peroxide
      (HP) with Ca and PO4; G6=7.5% HP with Ca. After each daily session of treatment,
      specimens were stored in distilled water (37 degrees C) until the next session.
      Products were applied for 2 weeks, according to manufacturers' instructions.
      Additional KHN weredetermined. RESULTS: Conventional whitening agents (G1; G2)
      and the gel with Ca (G6), caused KHN decrease (P< 0.05).The remineralizing and
      whitening agents with Ca and PO4 (G3; G4; G5) did not change KHN. A change of
      morphology was observed on enamel and dentin surfaces in G1; G2; G5.

PMID- 21874931
TI  - Effects of polishing on surface roughness, gloss and color of surface reaction
      type pre-reacted glass-ionomer filled resin composite.
AB  - PURPOSE: To evaluate the effects of polishing on surface roughness, gloss and
      color of different shades of surface reaction type pre-reacted glass-ionomer (S
      PRG) filled nano-hybrid resin composite. METHODS: Resin disks of 15 mm diameter
      and 2 mm thickness and final polish with 1000-grit SiC paper, super fine cut
      diamond (FG) point, silicon (MFR) point and Super-Snap mini-disk red (SNAP) were
      made with Beautifil II shades: A2, A20, Inc). One week after curing, the surface
      roughness, gloss and color were measured. Data was analyzed with ANOVA and
      Fisher's PLSD with alpha= 0.05 RESULTS: For all shades, the order of roughness
      (Ra) ranked according to groups of 1000-grit SiC > FG > MFR > SNAP with
      significant differences among all groups. For all shades, the order of gloss
      ranked according to groups of SNAP > MFR > FG > 1000-grit SiC with significant
      differences among the groups except for between MFR and FG without significant
      difference. The influence of the surface roughness on color differed among the
      polishing groups and shades. However, the values of the color differences
      (deltaE*ab) between the polishing groups of all shades were imperceptible to the
      naked eye.

PMID- 21874932
TI  - Comparative clinical study of coronally advanced flap with and without use of
      plasma rich in growth factors in the treatment of gingival recession.
AB  - PURPOSE: To evaluate the clinical efficiency of the coronally advanced flap (CAF)
      with and without plasma rich in growth factors (PRGF) in the management of
      gingival recession defects. METHODS: 20 bilateral similar recession defects in
      six healthy non-smoker subjects were included in the present study. The test
      sites received PRGF as an adjunct to the coronally advanced flap (CAF) while the
      control sites were treated with CAF only. The clinical parameters including
      recession depth (RD), percentage of root coverage (RC), recession width (RW),
      mucogingival junction position (MGJ), width of keratinized tissue (WKT), clinical
      attachment level (CAL), and probing depth (PD) were measured at the baseline, 1,
      and 3 months post-operatively. The data were analyzed using Wilcoxon signed rank
      and Mann-Whitney U tests. RESULTS: After 3 months, the mean root coverage was 43
      +/- 34.9% in the CAF group and 61 +/- 23.5%) in the CAF + PRGF. Both treatment
      protocols led to a significant improvement in all measured variables compared to
      the baseline values, except the width of keratinized tissue. While PRGF enhanced
      the outcomes of CAF especially throughout the first month post-operatively, it
      offered no clinical advantage over CAF alone during the subsequent 2 months.

PMID- 21874933
TI  - Occlusion of dentin tubules with antibacterial ammonium hexafluorosilicate
      solution for the prevention of dentin caries.
AB  - PURPOSE: To evaluate the degree of penetration of an ammonium hexafluorosilicate
      [SiF: (NH4)2SiF6] solution containing various antibacterial agents into dentin
      and the depth of dentin tubule occlusion by the precipitate. METHODS: Various
      antibacterial SiF solutions were prepared with the addition to chlorhexidine
      (CHX), cetylpyridinium chloride (CPC), isopropyl methylphenol (IPMP), or
      epigallocatechin gallate (EGCG), respectively. Two types of dentin disks were
      prepared from extracted teeth. One was a dentin surface covered with a smear
      layer, and the other treated with EDTA for 2 minutes to remove the smear layer
      and open dentin tubules. Then, the disks were treated with SiF solution with or
      without antibacterial agents for 3 minutes. The dentin surface and a
      longitudinally divided surface were observed with scanning electron microscopy
      (SEM) immediately after SiF treatment and after immersion in synthetic saliva for
      7 days. RESULTS: SEM photographs demonstrated that dentin tubules after treatment
      with SiF were occluded homogeneously and similar to those on conventional SiF
      treatment regardless of the addition of an antibacterial agent. However, the
      depth of occlusion became significantly shallower when SiF was applied to dentin
      specimens covered with a smear layer.

PMID- 21874934
TI  - The whole is greater than the sum of its parts: dental plaque bacterial
      interactions can affect the virulence properties of cariogenic Streptococcus
      mutans.
AB  - It has been well established that dental caries results from the accumulation of
      dental plaque on tooth surfaces. Several decades of in vitro and as well as
      clinical studies have identified Streptococcus mutans as an important etiological
      agent in carious lesion formation. In addition, a variety of approaches have
      suggested that interactions between the bacterial components of biofilms can
      influence the properties of such polymicrobial structures. Therefore, it is
      likely that the mere presence of S. mutans in dental plaque does not alone
      account for the cariogenic potential of such biofilms. Recent studies have
      indicated that several bacteria commonly found in dental plaque can influence
      either the viability and/or virulence properties of S. mutans. This review will
      summarize some of the more recent findings in this regard as well as their
      implications for the development of novel anti-caries strategies.

PMID- 21874935
TI  - Disinfection of toothbrushes contaminated with Streptococcus mutans.
AB  - PURPOSE: To determine the most effective method to kill Streptococcus mutans on
      contaminated toothbrushes. METHODS: Seven toothbrushes (one for each treatment
      and the control) were contaminated with S. mutans. Toothbrushes were then rinsed
      in phosphate buffered saline (PBS) and treated as follows: (1) control without
      treatment; (2) air dry for 4 hours; (3) Crest Pro-Health mouthwash for 20
      minutes; (4) Listerine mouthwash for 20 minutes; (5) normal cleaning cycle in a
      dishwasher; (6) microwave on high power for 5 minutes; and (7) ultraviolet light
      using the DenTek Toothbrush Sanitizer for 10 minutes. All toothbrushes were
      rinsed again with PBS. The bristles were cut and vortexed in PBS. Serial
      dilutions were performed and the number of colonies enumerated after incubation.
      The experiment was independently repeated seven times. RESULTS: The Crest Pro
      Health mouthwash and the dishwasher almost completely eliminated S. mutans. The
      second most effective treatment was the microwave. The Listerine mouthwash and
      the air dry groups were not significantly different from each other and ranked
      third. Although UV light significantly decreased the number of bacteria compared
      to the control, reduction in the number of S. mutans CFU was significantly lower
      than that of all the other treatments evaluated. Crest Pro-Health mouthwash for
      20 minutes and a normal dishwasher cycle are the most effective methods to
      eradicate S. mutans from contaminated toothbrushes. Dent

PMID- 21874936
TI  - Bonding ability of three ethanol-based adhesives after thermal fatigue.
AB  - PURPOSE: To study the effect of thermal fatigue on the microTBS and interfacial
      morphology of three ethanol-based etch-&-rinse 2-bottle adhesives. METHODS:
      microTBS - 24 third molars were randomly assigned to one of three adhesive
      systems: (1) Adper Single Bond Plus (SBP, 3M ESPE); (2) Ambar (AMB, FGM); (3)
      Excite (EXC, Ivoclar Vivadent), and restored with a hybrid resin composite. For
      each adhesive, half of the specimens were thermocycled (TC) for 20,000 cycles (5
      55 degrees C) while the other half was kept in distilled water for 24 hours at 37
      degreesC (control). Specimens were sectioned in X and Y directions and the
      resulting sticks were tested to failure in tension mode at a crosshead speed of 1
      mm/minute. Statistical analysis was computed using ANOVA and Tukey's post hoc for
      the microTBS; and non-parametric cross-tabulation with Chi-Square for the pre
      testing failures at P< 0.05. Interfacial morphology -The occlusal enamel was
      removed from 12 extracted molars perpendicular to the long axis of the tooth.
      Teeth were equally assigned to one of the three adhesives and restored with a 1
      mm-thick layer of a hybrid composite resin. A 2 mm-thick disk was sectioned from
      each specimen and cross-sectioned in two identical halves. Half of the each
      specimen was TC for 20,000 cycles (5-55 degrees C) while the other half was kept
      in distilled water for 24 hours at 37 degrees C (control). Specimens were
      chemically challenged and prepared for FESEM observation to observe the integrity
      of the hybrid layer before and after thermal fatigue. Micrographs were recorded
      digitally at standard magnifications and measurements were taken with the
      microscope embedded image software. RESULTS: microTBS - SBP and AMB resulted in
      statistically similar mean microTBS regardless of thermal fatigue. EXC resulted
      in statistically lower mean microTBS than SBP and AMB for the control (P< 0.001)
      and for the TC specimens (P< 0.0001). Interfacial morphology - The hybrid layers
      of SBP and AMB were densely infiltrated without interfacial failure. For EXC,
      extensive areas of debonding were observed between the adhesive layer and the
      hybrid layer both for the control and the TC groups. Thermal fatigue did not
      influence the bonding ability of AMB and SBP, but was detrimental for EXC.

PMID- 21874937
TI  - Effect of potential remineralizing agents on acid softened enamel.
AB  - PURPOSE: To assess whether pastes containing casein phosphopeptide-amorphous
      calcium phosphate (CPP-ACP) and calcium sodium phosphosilicate (CSP) protect acid
      softened enamel against further erosive episodes. METHODS: Enamel slabs of bovine
      teeth with preformed erosion-like lesions were randomly assigned to five
      treatment groups (n = 15): A) CPP-ACP (MI Paste, GC America); B) CPP-ACP+Fluoride
      (CPP-ACP+F, MI Plus Paste, GC America); C) CSP (Tooth Revitalizing Paste,
      Oravive); D) fluoridated dentifrice (FD, Sensodyne Cool Gel, GSK); E) control
      (CO, unexposed to any product). Paste treatments (1:3 slurry in deionized water
      or undiluted product in the case of the CPP-ACP formulae) were performed between
      five cycles of alternating erosive challenge (0.3% citric acid, pH = 3.2) and
      remineralization in artificial saliva. Specimens were analyzed by Knoop surface
      microhardness (SMH). RESULTS: ANOVA indicated a significant (P< 0.0001)
      difference among the SMH values attained by acid softened enamel following the
      exposure to the pastes interspersed with erosion-remineralization cycles. Tukey's
      test ascertained that SMH values observed for the CPP-ACP+F and CSP groups did
      not differ from that of FD group, which were significantly higher than that found
      for the CO group. Specimens treated with CPP-ACP did not differ from any of the
      other groups.

PMID- 21874938
TI  - Calcium phosphate-based solutions promote dentin tubule occlusions less
      susceptible to acid dissolution.
AB  - PURPOSE: To determine the efficacy supersaturated calcium phosphate (CaP)
      solutions containing fluoride (F) and zinc (Zn) ions in occluding dentin tubules
      with precipitates less susceptible to acid dissolution and to compare the
      performance of these solutions with the oxalate solutions containing calcium (Ca)
      or phosphate (P) ions. METHODS: Dentin sections from human molars divided into
      groups: Group A - control (treated with double distilled H2O), Groups A1, A2 and
      A3 were treated with experimental solutions supersaturated with respect to F and
      Zn-substituted calcium phosphates. Solutions A1 and A2 were similar in
      composition but differed in pH values (A1, pH 7; A2, pH 5.5). Solutions A2 and A3
      were similar in pH (pH 5.5) but the A3 solution had twice the concentrations of F
      and Zn2+ ions compared to A2. Another group of dentin sections were treated with
      A3 solution, oxalate solution containing Ca (OX/Ca) and OX solution containing P
      (OX/P). The control and treated dentin sections were characterized using scanning
      electron microscopy. RESULTS: All treated dentin sections showed occluded dentin
      tubules; with the group A3 showing the highest percent of occluded dentin
      tubules. The precipitates in the dentin tubules treated with A3 remained while
      those treated with OX/Ca or OX/P dissolved after exposure to an acidic buffer.

PMID- 21874939
TI  - Influence of tooth preparation burs on the roughness and bond strength of
      adhesives to human dentin surfaces.
AB  - PURPOSE: To characterize the surface roughness of human dentin prepared with
      different rotary instruments and its influence on the micro-tensile bond strength
      (microTBS) of self-etch adhesives. METHODS: Dentin surfaces were created from mid
      coronal sound dentin in extracted, human third molars. The teeth were ground with
      high-speed diamond, tungsten carbide finishing, and cross-cut carbide rotary
      instruments. Morphological changes obtained were investigated with a surface
      texture analyzer. Two additional specimens from each group were treated and
      prepared for scanning electron microscopy. Resin composite (Z 100) was bonded to
      the surfaces using Optibond FL (control), Adper Prompt L-Pop (strong), Clearfil
      SE Bond (mild), or Clearfil S3 Bond (ultra-mild). Rectangular micro-specimens
      were prepared using the slow-speed diamond saw and tested in tensile to determine
      the microTBS. The data were analyzed with one-way analysis of variance and
      Tukey's HSD test (alpha= 0.05). RESULTS: Surface preparation resulted in
      significant differences for surface topography and micro-tensile bond strength
      (P< 0.001). The cross-cut carbide burs had significantly higher mean roughness
      readings (SD) for all parameters: Ra [8.6 (1.9) microm], Rq [10.9 (2.2) microm],
      and Ry [41.1 (2.1) microm], except for the mean Rz [12.1 (3.1) microm] value,
      which was recorded for diamonds. The other roughness parameters for the diamond
      rotary instruments were intermediate. Dentin surfaces completed with tungsten
      carbide finishing burs produced a smoother surface Ra [1.2 (0.5) microm)] Rq
      ([1.6 (0.6) microm], Ry [6.4 (2.6) microm)] and Rz [1.9 (0.6) microm)]. The etch
      and-rinse adhesive (OptiBond FL) yielded high micro-tensile values (58.1-68.3
      MPa), irrespective of the rotary instruments used. The micro-tensile bond
      strength values were comparable for self-etch adhesives (Adper Prompt L-Pop,
      Clearfil SE Bond, Clearfil S3 Bond) irrespective of the burs used. The microTBS
      values were significantly higher with tungsten carbide finishing burs and smooth
      dentin surfaces.

PMID- 21874940
TI  - Noncarious cervical lesions (NCCL)--a clinical concept based on the literature
      review. Part 2: restoration.
AB  - PURPOSE: To present an updated knowledge on the restorative options and their
      performance in the particular environment of non-carious cervical lesions (NCCL).
      METHODS: Evidence-based support for a proper restoration of NCCL was searched.
      For this purpose, literature over the last 10 years available in the MEDLINE
      database was reviewed. Previous systematic reviews, meta-analysis and clinical
      trials as randomized clinical trials with a testing period of minimum 1 year were
      selected. RESULTS: Until recently, glass-ionomer-based materials were considered
      the treatment of choice in most of the NCCL, although consistent improvements are
      still required. Today, based on the excellent esthetic properties and the good
      clinical performance, there is a general indication to use composite in NCCL.
      Clinical behavior was found to be highly product-dependent. The choice of an
      adhesive with tested efficiency is decisive for the retention and marginal
      adaptation, whereas differences in flexibility were not found to be clinically
      important. A periodontal-esthetic approach was suggested by combining the
      surgical root coverage with the correction of the emergence profile by composite.

PMID- 21874941
TI  - Complex knee problems in a young, active duty military population. Part I: ACL
      reconstruction, allograft OATS, and treatment of meniscal injuries.

PMID- 21874942
TI  - Special considerations for ACL graft selection in the young, active military
      patient.
AB  - Anterior cruciate ligament (ACL) injury is an extremely common injury in the
      young, physically demanding active duty military population. The diagnosis of an
      ACL injury in active duty military personnel often requires special consideration
      in terms of return to function, reliability, and performance of the knee-often in
      life-threatening situations when one has to rely on a stable knee for survival.
      This article outlines the considerations of ACL surgical treatment in the active
      duty military population, with an emphasis on the young, physically competitive
      athlete to optimize outcomes. Numerous treatment options and controversies
      regarding ACL surgery will be reviewed to provide a framework for which to
      perform a reliable and effective ACL surgery in active duty military personnel.

PMID- 21874943
TI  - Technique: bone-patellar tendon-bone autograft ACL reconstruction in the young,
      active patient.
AB  - Successful treatment of the anterior cruciate ligament tear in the young, active
      population can be reliably achieved with an arthroscopic bone-patellar tendon
      bone (BTB) autograft reconstruction. Although some contraindications exist, the
      BTB autograft has been proven to provide for a durable, stable, and highly
      functional knee. Complications associated with the use of BTB can occur, but
      measures can be taken to minimize these risks. In addition to appropriate graft
      selection, meticulous surgical technique is required. This article outlines the
      step-by-step surgical technique including graft harvest, tunnel placement, graft
      preparation and passage, and interference screw fixation. Potential complications
      and the surgical decision-making options incurred are also discussed in detail.

PMID- 21874944
TI  - Treatment of meniscal injuries in young athletes.
AB  - The young, active patient with a meniscal tear poses a significant challenge for
      the surgeon. Multiple factors influence the treatment of meniscal pathology and
      the ultimate goal of meniscal surgery should be to remove only torn and
      nonfunctional tissue by limited meniscectomy or to repair amenable tears. The
      chondroprotective significance of the meniscus has influenced the current
      treatment of meniscal injuries in young athletes with the emphasis on repairing
      meniscus tears to include complex tears and tears in the avascular zone. Partial
      meniscectomy and meniscal repair techniques have provided good long-term clinical
      success and return to activity. The decision to debride versus repair a meniscus
      depends on tear pattern, location, and the patient's willingness to comply with
      postoperative restrictions. In patients with symptomatic meniscus deficiency,
      meniscal allograft transplant is an option that may provide pain relief but may
      not allow return to sports. The purpose of this article is to provide a succinct
      review of the diagnostic and management principles for the young, active patient
      with a meniscal tear.

PMID- 21874945
TI  - Allograft OATS: decision-making and operative steps.
AB  - Articular cartilage injuries present a challenge in terms of definitive treatment
      in an active population. There are many treatment options available, one of which
      being allograft osteochondral articular transplant (OAT), in patients with larger
      chondral injuries. When deciding to perform this procedure, one must be aware of
      preoperative and intraoperative findings that may change the treatment of a
      patient with a significant chondral injury. This article will discuss our
      preferred method of performing allograft OATS along with perioperative management
      and considerations of these patients.

PMID- 21874946
TI  - Comparison of interface stresses and strains for onlay and inlay unicompartmental
      tibial components.
AB  - There are several types of designs used for unicompartmental tibial components.
      The all-plastic inlay component is recessed and it preserves bone around the
      outer edge of the tibia. For an onlay component, the entire condyle is resected,
      and the plastic bearing is usually metal-backed, although all-plastic components
      are also available. The purpose of this study was to investigate the hypothesis
      that while 6-mm inlay components require less bone removal, the peak stresses and
      strains at the surface of the bone will be much greater when compared with 8-mm
      metal-backed onlay components, and that all-plastic onlays will be only a slight
      advantage over inlays. Tibial models were generated using computed tomography
      (CT) scans, while typical inlay and onlay components were modeled. Finite element
      analyses of bones and components were completed by assigning material properties
      based on the CT scans and applying loads. Results indicated that plastic inlays
      generated 6 times more peak stress at the tibial surface when compared with metal
      backed onlays. Moreover, models using inlay components produced strain values
      exceeding onlay components by a factor of 13.5 due to areas of softer bone at the
      interface. Off-center loading toward the anterior or posterior of the components
      produced similar results. The stresses and strains for the 8-mm all-plastic onlay
      were reduced compared with the inlay but still much higher than for the metal
      backed onlay. These findings indicated that metal-backed onlays may be a better
      option when considering load distribution on the tibial surface.

PMID- 21874947
TI  - Difference in stair negotiation ability based on TKA surgical approach.
AB  - Several surgical approaches for total knee arthroplasty (TKA) have been developed
      to minimize soft-tissue trauma and expedite functional recovery. A group of 61
      subjects undergoing computer-navigated, minimally invasive TKA were randomized to
      receive a mini-parapatellar, standard parapatellar, mini-midvastus (MV), or mini
      subvastus approach. Before and after treatment, subjects were asked to negotiate
      stairs in a self-selected manner. This study used the manner of stair negotiation
      (i.e., use of handrail, step-over-step, step-by-step) as a proxy for functional
      ability. Subjects who received TKA through a mini-MV approach demonstrated a
      significantly lower level of function at 2 and 4 months. If early functional
      recovery is a goal of TKA, surgeons should be cautious when considering the mini
      MV approach, which was found to be inferior to other approaches in this study.

PMID- 21874948
TI  - Articular cartilage surgery in outpatients: a pilot study.
AB  - Open knee surgery for the treatment of large symptomatic cartilage defects is
      routinely performed in the inpatient stay, where the patients are hospitalized
      for several days after surgery. This has implications for both costs for the
      health system and medical complications such as hospital-related infections. In
      this article, we describe for the first time that this type of operation can be
      performed as outpatient surgery without any complications for the patients and
      with good clinical results that in our sample do not differ from those reported
      in larger groups of patients who underwent surgery and were hospitalized
      thereafter.

PMID- 21874949
TI  - Extensor mechanism reconstruction: a novel technique for bone patella allograft
      post partial patellectomy failure.
AB  - Extensor mechanism disruption, whether due to patella fracture or tendon rupture,
      generally occurs after low-energy trauma and frequently involves an indirect
      mechanism. When the fracture is comminuted and reconstruction is impossible, a
      partial or total patellectomy may be indicated. Although some authors advocate
      total patellectomy, partial patellectomy remains the standard treatment,
      especially for young and active patients. In the rare instance of a failed tendon
      repair after partial or total patellectomy, inadequate tissue is usually
      available for adequate restoration of the extensor mechanism. Extensor mechanism
      allograft, using the tibial tuberosity, patellar tendon, patella, and quadriceps
      tendon in continuity or the Achilles' tendon with calcaneal bone-block in
      continuity has been reported for extensor mechanism repair after total knee
      arthroplasty in patients who did not undergo patellectomy. We present a novel
      technique, using the bone patellar tendon bone allograft to reconstruct a
      posttraumatic defect of the extensor mechanism in a 28-year-old, active patient
      with a failed partial patellectomy following fracture of his patella. Union of
      the allograft was seen on x-ray after 4 months. After 6 months, the patient
      reached full range of motion and returned to his previous sporting activities.

PMID- 21874950
TI  - Isolated popliteus rupture at the musculo-tendinous junction.
AB  - We report the case of a 23-year-old professional senior international rugby union
      player who sustained a lateral blow to his semiflexed knee during a competitive
      game. Initial clinical examination was unremarkable apart from some
      posterolateral tenderness. A magnetic resonance imaging scan showed an isolated
      popliteus tendon rupture at the musculo-tendinous junction. After 5 weeks of
      focused rehabilitation and graduated training, he was able to resume his playing
      career and resumed his international playing career later that season. At the
      time of reporting, he has completed a full domestic and international season
      without any sequelae from the injury. This report highlights the rarity of such
      an injury, especially at the musculo-tendinous junction, and sets out a detailed
      rehabilitation program that has enabled the patient in question to resume his
      playing career.

PMID- 21874951
TI  - Prospects for future climate change and the reasons for early action.

PMID- 21874952
TI  - An analysis of extinction coefficients of particles and water moisture in the
      stack after flue gas desulfurization at a coal-fired power plant.
AB  - Two important factors that affect in-stack opacity--light extinction by emitted
      particles and that by water moisture after a flue gas desulfurization (FGD) unit-
      are investigated. The mass light extinction coefficients for particles and water
      moisture, k(p) and k(w), respectively, were determined using the Lambert-Beer law
      of opacity with a nonlinear least-squares regression method. The estimated k(p)
      and k(w) values vary from 0.199 to 0.316 m2/g and 0.000345 to 0.000426 m2/g,
      respectively, and the overall mean estimated values are 0.229 and 0.000397 m2/g,
      respectively. Although k(w) is 3 orders of magnitude smaller than k(p),
      experimental results show that the effect on light extinction by water moisture
      was comparable to that by particles because of the existence of a considerable
      mass of water moisture after a FGD unit. The mass light extinction coefficient
      was also estimated using Mie theory with measured particle size distributions and
      a complex refractive index of 1.5-ni for fly ash particles. The k(p) obtained
      using Mie theory ranges from 0.282 to 0.286 m2/g and is slightly greater than the
      averaged estimated k(p) of 0.229 m2/g from measured opacity. The discrepancy may
      be partly due to a difference in the microstructure of the fly ash from the
      assumption of solid spheres because the fly ash may have been formed as spheres
      attached with smaller particles or as hollow spheres that contained solid
      spheres. Previously reported values of measured k(p) obtained without considering
      the effects of water moisture are greater than that obtained in this study, which
      is reasonable because it reflects the effect of extinction by water moisture in
      the flue gas. Additionally, the moisture absorbed by particulate matter,
      corresponding to the effect of water moisture on the particulates, was clarified
      and found to be negligible.

PMID- 21874953
TI  - Validation of an evacuated canister method for measuring part-per-billion levels
      of chemical warfare agent simulants.
AB  - The National Institute for Occupational Safety and Health (NIOSH) research on
      direct-reading instruments (DRIs) needed an instantaneous sampling method to
      provide independent confirmation of the concentrations of chemical warfare agent
      (CWA) simulants. It was determined that evacuated canisters would be the method
      of choice. There is no method specifically validated for volatile organic
      compounds (VOCs) in the NIOSH Manual of Analytical Methods. The purpose of this
      study was to validate an evacuated canister method for sampling seven specific
      VOCs that can be used as a simulant for CWA agents (cyclohexane) or influence the
      DRI measurement of CWA agents (acetone, chloroform, methylene chloride, methyl
      ethyl ketone, hexane, and carbon tetrachloride [CCl4]). The method used 6-L
      evacuated stainless-steel fused silica-lined canisters to sample the atmosphere
      containing VOCs. The contents of the canisters were then introduced into an
      autosampler/preconcentrator using a microscale purge and trap (MPT) method. The
      MPT method trapped and concentrated the VOCs in the air sample and removed most
      of the carbon dioxide and water vapor. After preconcentration, the samples were
      analyzed using a gas chromatograph with a mass selective detector. The method was
      tested, evaluated, and validated using the NIOSH recommended guidelines. The
      evaluation consisted of determining the optimum concentration range for the
      method; the sample stability over 30 days; and the accuracy, precision, and bias
      of the method. This method meets the NIOSH guidelines for six of the seven
      compounds (excluding acetone) tested in the range of 2.3-50 parts per billion
      (ppb), making it suitable for sampling of these VOCs at the ppb level.

PMID- 21874954
TI  - Facility fence-line monitoring using passive samplers.
AB  - In 2009, the U.S. Environmental Protection Agency (EPA) executed a year-long
      field study at a refinery in Corpus Christi, TX, to evaluate the use of passive
      diffusive sampling technology for assessing time-averaged benzene concentrations
      at the facility fence line. The purpose of the study was to investigate the
      implementation viability and performance of this type of monitoring in a real
      world setting as part of EPA's fence-line measurement research program. The study
      utilized 14-day, time-integrated Carbopack X samplers deployed at 18 locations on
      the fence line and at two nearby air monitoring sites equipped with automated gas
      chromatographs. The average fence-line benzene concentration during the study was
      1075 parts per trillion by volume (pptv) with a standard deviation of 1935 pptv.
      For a 6-month period during which wind direction was uniform, the mean
      concentration value for a group of downwind sites exceeded the mean value of a
      similar upwind group by 1710 pptv. Mean value differences for these groups were
      not statistically significant for the remaining 6-month time period when wind
      directions were mixed. The passive sampling approach exhibited acceptable
      performance with a data completeness value of 97.1% (n = 579). Benzene
      concentration comparisons with automated gas chromatographs yielded an r2 value
      of 0.86 and a slope of 0.90 (n = 50). A linear regression of duplicate pairs
      yielded an r2 of 0.97, unity slope, and zero intercept (n = 56). In addition to
      descriptions of technique performance and general results, time-series analyses
      are described, providing insight into the utility of 2-week sampling for source
      apportionment under differing meteorological conditions. The limitations of the
      approach and recommendations for future measurement method development work are
      also discussed.

PMID- 21874955
TI  - Visual range trends in the Yangtze River Delta Region of China, 1981-2005.
AB  - Visual range (VR) data from 1981 to 2005 were examined for 20 meteorological
      monitoring sites in the Yangtze River Delta Region of China. Cumulative
      percentile analysis was used to construct VR trend. The 25-yr average domain
      average 50% VR was approximately 21.9 +/- 1.9 km. Domain-average 50% VR decreased
      from 1981 to 2005 with a trend of -2.41 km/decade. The worst 20% and 50% and best
      20% VR and variation rates for the 20 sites were analyzed. The 50% VR of the
      town, county-level city, and prefecture-level city sites were 24.1, 21.5, and
      19.4 km, respectively. The best 20% VR decreased fastest with a rate of -3.5
      km/decade. Regional median VR decreased from the coastal sites to the inland
      sites. Ridit analysis and cumulative percentile were adopted to study the VR
      variation properties between economically developed areas (e.g., Nanjing and
      Hangzhou) and remote areas (e.g., Lvsi). The two analyses show that VR decreased
      in Nanjing and Hangzhou but remained constant in Lvsi from 1981 to 2005.

PMID- 21874956
TI  - Assessment and distribution of antimony in soils around three coal mines, Anhui,
      China.
AB  - Thirty-three soil samples were collected from the Luling, Liuer, and Zhangji coal
      mines in the Huaibei and Huainan areas of Anhui Province, China. The samples were
      analyzed for antimony (Sb) by inductively coupled plasma-optical emission
      spectrometry (ICP-OES) method. The average Sb content in the 33 samples was 4 mg
      kg(-1), which is lower than in coals from this region (6.2 mg kg(-1)). More than
      75% of the soils sampled showed a significant degree of Sb pollution (enrichment
      factors [EFs] 5-20). The soils collected near the gob pile and coal preparation
      plant were higher in Sb content than those collected from residential areas near
      the mines. The gob pile and tailings from the preparation plant were high in
      mineral matter content and high in Sb. They are the sources of Sb pollution in
      surface soils in the vicinity of coal mines. The spatial dispersion of Sb in
      surface soil in the mine region shows that Sb pollution could reach out as far as
      350 m into the local environment conditions. Crops in rice paddies may adsorb
      some Sb and reduce the Sb content in soils from paddyfields. Vertical
      distribution of Sb in two soil profiles indicates that Sb is normally relatively
      immobile in soils.

PMID- 21874958
TI  - Design and characterization of a two-stage human subject exposure chamber.
AB  - A human subject exposure chamber, designed to hold six to eight subjects, coupled
      to an approximately 30-m3 Teflon reaction bag was designed and built to provide
      exposures that mimic the production and photochemical oxidation of atmospheric
      pollutants resulting from the combustion of coal or wood from a stove. The
      combustion products are introduced into the Teflon bag under atmospheric
      conditions. Photochemical oxidation of this mixture is accomplished by exposure
      to tropospheric sun-like radiation from an array of ultraviolet and black lamps.
      The aerosol in the Teflon reaction bag is then transferred into the exposure room
      to maintain a constant, lower exposure level. Continuous and semicontinuous
      monitoring of the gas and particulate matter (PM) pollution in the exposure room
      and the reaction bag is accomplished using a suite of instruments. This suite of
      instruments allows for the measurement of the concentrations of total and
      nonvolatile PM, nitric oxide, nitrogen dioxide, carbon monoxide, carbon dioxide,
      and ozone. The concentration of the particles was monitored by an R&P tapered
      element oscillating microbalance monitor. The chemical composition of the PM and
      its morphological characterization is accomplished by collecting samples in
      filter packs and conducting ion chromatography, elemental X-ray fluorescence, and
      scanning electron microscopy analyses. The concentration and composition of
      emissions from combustion of wood and coal is described. The results of this
      study suggest that although the bulk compositions of particulate emissions from
      the combustion of coal or wood in a stove have many similarities, the wood smoke
      aerosol is photochemically reactive, whereas the coal smoke aerosol is not.

PMID- 21874957
TI  - Vascular function and short-term exposure to fine particulate air pollution.
AB  - Exposure to fine particulate air pollution has been implicated as a risk factor
      for cardiopulmonary disease and mortality. Proposed biological pathways imply
      that particle-induced pulmonary and systemic inflammation play a role in
      activating the vascular endothelium and altering vascular function. Potential
      effects of fine particulate pollution on vascular function are explored using
      controlled chamber exposure and uncontrolled ambient exposure. Research subjects
      included four panels with a total of 26 healthy nonsmoking young adults. On two
      study visits, at least 7 days apart, subjects spent 3 hr in a controlled-exposure
      chamber exposed to 150-200 microg/m3 of fine particles generated from coal or
      wood combustion and 3 hr in a clean room, with exposure and nonexposure periods
      alternated between visits. Baseline, postexposure, and post-clean room reactive
      hyperemia-peripheral arterial tonometry (RH-PAT) was conducted. A microvascular
      responsiveness index, defined as the log of the RH-PAT ratio, was calculated.
      There was no contemporaneous vascular response to the few hours of controlled
      exposure. Declines in vascular response were associated with elevated ambient
      exposures for the previous 2 days, especially for female subjects. Cumulative
      exposure to real-life fine particulate pollution may affect vascular function.
      More research is needed to determine the roles of age and gender, the effect of
      pollution sources, the importance of cumulative exposure over a few days versus a
      few hours, and the lag time between exposure and response.

PMID- 21874959
TI  - Odor emission rate estimation of indoor industrial sources using a modified
      inverse modeling method.
AB  - Odor emission rates are commonly measured in the laboratory or occasionally
      estimated with inverse modeling techniques. A modified inverse modeling approach
      is used to estimate source emission rates inside of a postdigestion centrifuge
      building of a water reclamation plant. Conventionally, inverse modeling methods
      divide an indoor environment in zones on the basis of structural design and
      estimate source emission rates using models that assume homogeneous distribution
      of agent concentrations within a zone and experimentally determined link
      functions to simulate airflows among zones. The modified approach segregates
      zones as a function of agent distribution rather than building design and
      identifies near and far fields. Near-field agent concentrations do not satisfy
      the assumption of homogeneous odor concentrations; far-field concentrations
      satisfy this assumption and are the only ones used to estimate emission rates.
      The predictive ability of the modified inverse modeling approach was validated
      with measured emission rate values; the difference between corresponding
      estimated and measured odor emission rates is not statistically significant.
      Similarly, the difference between measured and estimated hydrogen sulfide
      emission rates is also not statistically significant. The modified inverse
      modeling approach is easy to perform because it uses odor and odorant field
      measurements instead of complex chamber emission rate measurements.

PMID- 21874960
TI  - Characteristics of microbial aerosols released from chicken and swine feces.
AB  - Bioaerosols generated during livestock and poultry production are significant
      occupational hazards. This study investigates the characteristics of bioaerosols
      released from animal feces. Fresh feces from pigs and chickens were obtained and
      tested in a controlled-environment facility. Airborne viable (culturable)
      bacteria and fungi were sampled hourly for 48 hr. The predominant species were
      identified via polymerase chain reaction analysis. The number of bacterial
      colonies released from chicken feces increased gradually, peaked at approximately
      20 hr, and remained relatively constant to test end; however, the bacterial
      colonies released from swine feces did not increase significantly. The chicken
      feces released significantly (P < 0.05) more bacterial aerosols than swine feces
      over 40 hr, by approximately 1 order of magnitude. However, the difference in
      total fungal aerosols released from the two feces types was relatively small (30
      40%) and insignificant (P > 0.05). Aerosols sized between approximately 0.65 and
      1.1 microm were predominant for bacteria, whereas aerosols sized between
      approximately 2.1 and 3.3 microm prevailed for fungi. Genera Stenotrophomonas
      were the predominant bacterial aerosols, whereas Cladosporium and Acremonium
      accounted for the greatest amounts of fungi from chicken and swine feces,
      respectively. More than 1000 culturable bacterial colonies can be released from 1
      g of chicken feces per hour, and approximately 80% of these bioaerosols are
      respirable. Most bacterial aerosols released from swine and chicken feces were
      opportunistic human pathogens; thus, the significance of their presence warrants
      further investigations.

PMID- 21874961
TI  - Advancing efficiency. 2011 hospital energy management survey.

PMID- 21874962
TI  - Energy innovations with an eye on the bottom line.

PMID- 21874963
TI  - History lessons. How post-occupancy evaluations can benefit interior design
      projects.

PMID- 21874964
TI  - Getting ahead. Developing a 'chief facilities officer' mindset.

PMID- 21874965
TI  - Gaining traction. New resilient flooring products contribute to hospital design
      trends.

PMID- 21874966
TI  - Open to change. It's proposal time for the 2014 FGI Guidelines.

PMID- 21874967
TI  - Finding cleaning fixes. Evaluating technology to help fight the spread of
      infection.

PMID- 21874968
TI  - Team training can enhance patient safety--the data, the challenge ahead.

PMID- 21874969
TI  - Twelve best practices for team training evaluation in health care.
AB  - BACKGROUND: Evaluation and measurement are the building blocks of effective skill
      development, transfer of training, maintenance and sustainment of effective team
      performance, and continuous improvement. Evaluation efforts have varied in their
      methods, time frame, measures, and design. On the basis of the existing body of
      work, 12 best practice principles were extrapolated from the science of
      evaluation and measurement into the practice of team training evaluation. Team
      training evaluation refers to efforts dedicated to enumerating the impact of
      training (1) across multiple dimensions, (2) across multiple settings, and (3)
      over time. Evaluations of efforts to optimize teamwork are often afterthoughts in
      an industry that is grounded in evidence-based practice. The best practices
      regarding team training evaluation are provided as practical reminders and
      guidance for continuing to build a balanced and robust body of evidence regarding
      the impact of team training in health care. THE 12 BEST PRACTICES: The best
      practices are organized around three phases of training: planning,
      implementation, and follow-up. Rooted in the science of team training evaluation
      and performance measurement, they range from Best Practice 1: Before designing
      training, start backwards: think about traditional frameworks for evaluation in
      reverse to Best Practice 7: Consider organizational, team, or other factors that
      may help (or hinder) the effects of training and then to Best Practice 12: Report
      evaluation results in a meaningful way, both internally and externally.
      CONCLUSIONS: Although the 12 best practices may be perceived as intuitive, they
      are intended to serve as reminders that the notion of evidence-based practice
      applies to quality improvement initiatives such as team training and team
      development as equally as it does to clinical intervention and improvement
      efforts.

PMID- 21874970
TI  - On the front lines of patient safety: implementation and evaluation of team
      training in Iraq.
AB  - BACKGROUND: Team training has been identified as a key strategy for reducing
      medical errors and building a culture of safety in health care. Communication and
      coordination skills can serve as barriers to potential errors, as in the modern
      deployed U.S. Military Healthcare System (MHS), which emphasizes rapid movement
      of critically injured patients to facilities capable of providing definitive
      care. A team training intervention--TeamSTEPPS--was implemented on a large scale
      during one of the most intense phases of the conflict in Iraq. This evaluation of
      the program constituted the first undertaken in a combat theater of operations.
      IMPLEMENTING TEAMSTEPPS IN IRAQ: The Baghdad combat support hospital (CSH)
      conducted continuous operations from a fixed facility for a 13-month deployment-
      between November 2007 and December 2008. The TeamSTEPPS implementation in Iraq
      began at this facility and spread throughout the combat theater of operations.
      Teamwork training was implemented in two primary training sessions, followed up
      with reinforcement of team behaviors on the unit by hospital leadership. RESULTS:
      A total of 153 patient safety reports were submitted during the 13 months
      reviewed, 94 before TeamSTEPPS implementation and 59 afterwards. After training,
      there were significant decreases in the rates of communication-related errors,
      medication and transfusion errors, and needlestick incidents. There was a
      significant decrease in the rate of incidents coded communication as the primary
      teamwork skill that could have potentially prevented the event. CONCLUSIONS:
      Process improvement programs such as TeamSTEPPS implementation can be conducted
      under the extremely austere conditions of a CSH in a combat zone. Teamwork
      training decreased medical errors in the CSH while deployed in the combat theater
      in Iraq.

PMID- 21874971
TI  - Didactic and simulation nontechnical skills team training to improve perinatal
      patient outcomes in a community hospital.
AB  - BACKGROUND: Birth trauma is a low-frequency, high-severity event, making
      obstetrics a major challenge for patient safety. Yet, few strategies have been
      shown to eliminate preventable perinatal harm. Interdisciplinary team training
      was prospectively evaluated to assess the relative impact of two different
      learning modalities to improve nontechnical skills (NTS)--the cognitive and
      interpersonal skills, such as communication and teamwork, that supplement
      clinical and technical skills and are necessary to ensure safe patient care.
      METHODS: Between 2005 and 2008, perinatal morbidity and mortality data were
      prospectively collected using the Weighted Adverse Outcomes Score (WAOS) and a
      culture of safety survey (Safety Attitudes Questionnaire) at three small-sized
      community hospitals. In a small cluster randomized clinical trial conducted in
      the third quarter of 2007, one of the hospitals served as a control group and two
      served as the treatment intervention sites--one hospital received the TeamSTEPPS
      didactic training program and one hospital received both the TeamSTEPPS program
      along with a series of in-situ simulation training exercises. RESULTS: A
      statistically significant and persistent improvement of 37% in perinatal
      morbidity was observed between the pre- and postintervention for the hospital
      exposed to the simulation program. There were no statistically significant
      differences in the didactic-only or the control hospitals. Baseline perceptions
      of culture of safety were high at all three hospitals, and there were no
      significant changes. CONCLUSIONS: A comprehensive interdisciplinary team training
      program using in-situ simulation can improve perinatal safety in the hospital
      setting. This is the first evidence providing a clear association between
      simulation training and improved patient outcomes. Didactics alone were not
      effective in improving perinatal outcomes.

PMID- 21874972
TI  - Evaluating efforts to optimize TeamSTEPPS implementation in surgical and
      pediatric intensive care units.
AB  - BACKGROUND: An evidence-based teamwork system, Team-STEPPS, was implemented in an
      academic medical center's pediatric and surgical ICUs. METHODS: A
      multidisciplinary change team of unit- and department-based leaders was formed to
      champion the initiative; develop a customized action plan for implementation;
      train frontline staff; and identify process, team outcome, and clinical outcome
      objectives for the intervention. The evaluation consisted of interviews with key
      staff, teamwork observations, staff surveys, and clinical outcome data. RESULTS:
      All PICU, SICU, and respiratory therapy staff received TeamSTEPPS training. Staff
      reported improved experience of teamwork posttraining and evaluated the
      implementation as effective. Observed team performance significantly improved for
      all core areas of competency at 1 month postimplementation and remained
      significantly improved for most of the core areas of competency at 6 and 12
      months postimplementation. Survey data indicated improvements in staff
      perceptions of teamwork and communication openness in both units. From pre- to
      posttraining, the average time for placing patients on extracorporeal membrane
      oxygenation (ECMO) decreased significantly. The average duration of adult surgery
      rapid response team events was 33% longer at postimplementation versus pre
      implementation. The rate of nosocomial infections at postimplementation was below
      the upper control limit for seven out of eight months in both the PICU and the
      SICU. CONCLUSIONS: The implementation of a customized 2.5-hour version of the
      TeamSTEPPS training program in two areas--the PICU and SICU--that had
      demonstrated successful ability to innovate suggests that the training was
      successful.

PMID- 21874973
TI  - Investigating a pediatric hospital's response to an inpatient census surge during
      the 2009 H1N1 influenza pandemic.
AB  - BACKGROUND: On November 4, 2009, the 250-bed Seattle Children's Hospital (SCH)
      identified a surge in its census--245 inpatients, well above the average midnight
      census of 207. In response, SCH activated its pandemic influenza surge plan in an
      effort to decrease the inpatient census. Within 16 hours, 51 patients (20.4% of
      total bed capacity) had been discharged, and inpatient census at SCH decreased to
      222 patients. METHODS: As part of a quality improvement project, SCH's response
      to the surge was investigated, with data drawn from interviews, a review of
      records created in the course of the surge plan implementation, an e-mail survey
      of attending physicians responsible for patient discharges, and models examining
      predictors of hospital discharges. FINDINGS: Analysis of three years of hospital
      data (2007-2009) indicated that the high census on November 4 was an uncommon but
      not unprecedented occurrence. In addition, there was a clear positive association
      between an evening's census and the number of discharges during the following 24
      hours. SCH discharged essentially the same number of patients on November 4 as on
      previous high-census days when the surge plan was not activated, suggesting that
      the surge plan did not succeed in creating excess discharges. CONCLUSIONS:
      Increasingly, evidence indicates that care quality depends on the degree to which
      hospital resources are sufficient to meet demand. Reverse triage, at least as
      implemented by SCH on November 4, 2009, is unlikely to represent an effective
      solution to surge outside of a disaster setting because of its requirement for
      centralized decision making. SCH has incorporated the results of this review into
      the way that it collects and analyzes data, manages flow, and responds to
      inpatient surges.

PMID- 21874974
TI  - Very long term concerns.

PMID- 21874975
TI  - FR garment program development: easier said than done.
AB  - Budget pressures are relatively common these days, and this may entice purchasing
      departments to look only at the initial cost of an FR garment. But there is more
      to it than that, especially for protective clothing. To make the best choice for
      safety and economy, check the details for yourself and make sure you get the best
      protection, comfort, and value for your money.

PMID- 21874976
TI  - Global classification systems for chemical protective apparel.

PMID- 21874977
TI  - Is grip the new safety feature?

PMID- 21874978
TI  - Safety and warehouse storage.

PMID- 21874979
TI  - Key elements of OSHA's cranes & derricks standard.

PMID- 21874980
TI  - What can go wrong in confined space rescues, part 2.

PMID- 21874981
TI  - Eight tips for chemical safety.

PMID- 21874982
TI  - Gluten-free leadership.

PMID- 21874983
TI  - Skill mix review: a well used term to facilitate safe, flexible, effective care
      delivery or a means of compromising perioperative professionalism?
AB  - The urgent need for safe and cost effective care is paramount in these
      challenging times given the stated deficit of 20 billion pounds real terms
      investment over the next three years (DH 2010).

PMID- 21874984
TI  - Communication: why is this such an emotive subject?
AB  - Communication is the activity of conveying meaningful information. Communication
      requires a sender, a message and an intended recipient, although the receiver
      need not be present or aware of the sender's intent to communicate at the time of
      communication; thus communication can occur across vast distances in time and
      space. Communication requires that the communicating parties share an area of
      communicative commonality. The communication process is complete once the
      receiver has understood the sender.

PMID- 21874985
TI  - Perioperative communication: the surgical safety checklist.

PMID- 21874986
TI  - Perioperative management of morbid obesity.
AB  - Data from the NHS Information Centre reveals that more than one in three adults
      (36.9%) is overweight. In addition, almost a quarter of adults (24% of men and
      25% of women aged 16 or over) are obese, with their need for treatment placing a
      growing burden on the NHS (The NHS Information Centre 2010). Given these
      proportions, and that an increasing number of morbidly obese patients are
      undergoing weight loss surgery and procedures related to obesity, it is an
      opportune time to review the perioperative care of morbidly obese patients.

PMID- 21874987
TI  - Cricoid pressure: a review of the literature.
AB  - Aspiration pneumonitis (Mendelson's syndrome) is universally accepted as a
      complication of general anaesthesia. According to Ellis et al (2007) death from
      aspiration was first described by Simpson in 1848, and it was not until 1946 that
      Mendelson identified acid aspiration in a significant number of obstetric
      patients undergoing facemask anaesthesia. The advent of techniques to secure the
      airway, through the use of airway adjuncts has gone some way to reduce the likely
      incidence of aspiration in today's perioperative arena. The positive outcome for
      patients is corroborated by Neilipovitz & Crosby (2007) who report aspiration as
      a rare complication with an overall incidence of 1:2,000-3,000. As Ewart (2007)
      highlights, Mendelson's syndrome is due to pharmacological effects at a molecular
      level which occur in the airway tissues and are caused by the use of induction
      and neuromuscular blocking agents. The resultant loss of consciousness and
      consequent diminished protective airway reflexes ultimately places the patient at
      risk until their airway is secured. Preventative measures to protect the lung
      from contamination with gastric contents, for example preoperative fasting, are
      therefore instigated prior to securing the airway.

PMID- 21874988
TI  - Optimising perioperative patient care: 'enhanced recovery' following colorectal
      surgery.
AB  - The concept of 'enhanced recovery' following elective surgery is becoming
      increasingly prominent in the world of perioperative practice. Enhanced recovery
      pathways (ERP) are being implemented in more and more trusts throughout the UK,
      and in multiple different surgical specialties. But what does enhanced recovery
      actually mean and how does it impact upon both patients and healthcare
      professionals? Our unit has been using an ERP in colorectal surgery since 2007
      and we are currently in the process of implementing a pathway for both our
      orthopaedic and gynaecological patients. This article comprises some background
      information on the evolution of enhanced recovery, a summary of its key elements
      and a review of the evidence, including a look at our unit's experience.

PMID- 21874989
TI  - The perceived effectiveness of a pre-admission visit for children (and their
      parents) undergoing day surgery procedures.
AB  - The purpose of this paper is to present the findings of an evaluation study which
      examines the perceived effectiveness of a pre-admission visit for children (and
      their parents) undergoing day surgery procedures in the Republic of Ireland. This
      follow on paper provides the findings of an evaluation study subsequent to the
      pre-admission, practice development initiative published in the Journal of
      Perioperative Practice, June 2010, 20 (6) 203-206.

PMID- 21874990
TI  - No formalin please, it could be TB!
AB  - Historically, tuberculosis (TB) in the UK was primarily associated with pulmonary
      infection. However, as the rates of TB in the UK have risen, so has the
      proportion of extra pulmonary disease. In 1987, the total number of new TB cases
      was 5,085 and 21% of these were extra pulmonary. By 2009, the annualnumber of TB
      cases had risen to 9,040 with 46% being extra pulmonary (HPA 2010).

PMID- 21874991
TI  - The early days of splints and splinting.
AB  - There can be little doubt that fractures and wounds would have been among the
      first problems that the healers within primitive communities would have been
      called upon to treat. Indeed, this has been amply confirmed by anthropologists
      and archaeologists. The Australian aboriginals seem to have taken the adage
      'splint the patient where he lies' quite literally. Early observers saw the
      relatives take it in turns simply to hold the injured leg still until union
      occurred, a shelter being erected over the patient and his succession of 'human
      splints'. The excavation of ancient Egyptian burial sites by Sir Grafton Elliot
      Smith in the early years of the 20th century revealed fractures of some 5000
      years ago, bound up in splints of bark, wrapped in linen and held by bandages.
      Where the fractures were compound, dressings of vegetable fibre were used to plug
      the wound and some still showed traces of 50 century old blood!

PMID- 21874992
TI  - Testing reality during adolescence: the contribution of Erikson's concepts of
      fidelity and developmental actuality.
AB  - The process of reality testing can be thought of as a lifespan developmental
      line, where adolescence provides a critical developmental advance but not an
      endpoint. Erikson's concepts of fidelity and developmental actuality provide a
      frame of reference for considering this. Three means of reality testing are
      identified--contemplation, action, and conversation--where these modes of
      approach can be used separately or in concert to clarify the reality status of
      situations and phenomena. These methods of testing reality are illustrated within
      four arenas of adolescent functioning-thought, time, parental representations,
      and the experience of the embodied self.

PMID- 21874993
TI  - The living body in the psychoanalytic experience.
AB  - Instead of viewing body and psyche as two "substances," the author proposes that
      they be seen as two ways of experiencing the complex reality of the human being.
      Clinically, this translates into an exploration of the possibility of including
      the somatic in the territory of what can be represented--that is, recognizing in
      somatic and sensory elements and in bodily functions the potential for meaning
      and language, appreciating their status as precursors of representation. These
      somatic signals may be detected in a dialogue involving not only the minds of
      analyst and analysand, but also their bodies. Clinical examples are given
      involving different bodily functions.

PMID- 21874994
TI  - Seduction and revenge in Virginia Woolf's Orlando.
AB  - Virginia Woolf's Orlando was characterized by Nigel Nicolson as a "charming love
      letter" to his mother, Vita Sackville-West. The fictional biography was actually
      an attempt by Woolf to organize herself after the unbearable humiliation of
      Vita's abandoning her for another woman. In imagining, writing, and publishing
      Orlando, Woolf turns her despair about Vita's betrayal into a monument of
      revenge, defending against disorganizing feelings of humiliation, powerlessness,
      rage, and loss by creating her own scathing portrait of Vita. In the novel, Woolf
      also intermittently merges herself with Orlando/Vita to create a permanent tie to
      the woman who--like her mother and sister--excited and rejected her.

PMID- 21874995
TI  - Telephone analysis: compromised treatment or an interesting opportunity?
AB  - Under the pressure of societal changes, today many analysts agree to conduct
      parts of an analysis over the telephone. However, little has been written about
      particular ways in which use of the phone affects the psychoanalytic process. The
      author focuses on the impact of the phone on psychoanalytic treatment and
      particularly on one of its potential advantages, i.e., the combination of a
      continuity that intensifies the treatment and physical distance between analyst
      and patient, making this intensity less threatening. Two detailed case reports
      illustrate how this combination facilitated the growth of affective tolerance and
      enabled these two patients to bring their emotional experiences from phone
      sessions into the consulting room.

PMID- 21874996
TI  - Excogitating Bion's Cogitations: further implications for technique.
AB  - The author takes up a number of Bion's musings posthumously published as
      Cogitations (1992) and attempts to demonstrate the clinical usefulness of Bion's
      thoughts. She offers some new models and some points of technique that might be
      derived from following the trail of these selected fragments of Bion's thinking.
      Several detailed clinical examples are offered for clarification and
      illustration.

PMID- 21874997
TI  - The last of life: psychological reflections on old age and death.
AB  - A long-retired psychoanalyst considers his old age and bereavement and the brief
      span of life remaining. The greater imminence of death now than at any earlier
      time in life calls for more than currently available satisfactions, however
      rewarding they may be. Seeing life as a whole is now a possibility, while the
      death of his wife reveals more than ever their interrelatedness as a pair and
      strengthens the hope of continuity.

PMID- 21874998
TI  - Who is in charge of space and time?

PMID- 21874999
TI  - [Cardiovascular diseases and rheumatoid arthritis].
AB  - Morbidity and mortality rates are higher in rheumatoid arthritis (RA) patients
      than in the general population. RA is associated with an increased risk of
      cardiovascular disease. All of the cardiac structures can be affected during the
      course of RA. Rheumatoid arthritis, per se, is a cardiovascular (CV) risk factor
      as arterial hypertension, dyslipidemia and diabetes etc. Although the increased
      CV risk is acknowledged, limited attention is paid to detecting and managing CV
      comorbid conditions. Early identification, adequate CV risk management and
      ongoing monitoring of risk factors are mandatory to reduce the CV risk. Also,
      adequate control of arthritis disease activity is necessary to lower CV risk.

PMID- 21875000
TI  - [Physical therapy in rheumatology].
AB  - Rheumatic diseases are the leading cause of chronic disability. Physical therapy
      and rehabilitation are an integral part of the strategy of treatment of rheumatic
      diseases in order to maintain the function of the musculoskeletal system. Early
      detection of disability provides a more efficient implementation of all measures
      of physiotherapy treatment. Exercises are the most important form of
      physiotherapy. Long-term effect of exercise is possible only if patients achieve
      adherence to the program. Questionnaires activities of daily living asses
      functional status of patients, can be a guide for planning the rehabilitation
      program and indicator of the effectiveness of therapeutic intervention as well.
      Methods of physical therapy and rehabilitation are part of all published
      guidelines for the management of rheumatoid arthritis, spondyloarthritides,
      osteoarthritis, osteoporosis, chronic back pain, chronic non-malignant pain and
      fibromyalgia.

PMID- 21875001
TI  - [Non-pharmacologic treatment of rheumatoid arthritis].
AB  - Non-pharmacologic interventions are the part of comprehensive therapy of
      rheumatoid arthritis, proposed by all guidelines and recommendations. Patients
      with rheumatoid arthritis have pain, limited joint mobility, and impaired quality
      of life. Physical modalities are prescribed exactly with idea to diminish pain,
      iprove joint mobility and quality of life. Physical procedures are generally safe
      and well tolerated.

PMID- 21875002
TI  - [Physical therapy in osteoarthritis].
AB  - Physical therapy has an important role in treating rheumatic diseases; its goal
      is to reduced pain, swelling and to keep joints mobile. The properly manage
      osteoarthritis is nonpharmacological and pharmacological modalities. Physical
      therapy applied as a remedy for osteoarthritis is a part of multimodal therapy.
      The basis for physical therapy management is determined by the recommendation of
      the physical therapeutic science and evidence-based medicine. When making a
      decision about application of different methods of treatment in physical therapy,
      it is important to correctly diagnose a structural transformation and functional
      problem. Systematic review of the scientific, evidence-based, international
      concensus recommendations for the management of the osteoarthritis published
      between 2000 and 2010 were identified high-quality evidence therapy practice that
      is efficient and effective in increasing movement capability function, and reduce
      pain, disability, medical intake and improved physical function for patients with
      osteoarthritis

PMID- 21875003
TI  - [Spondyloarthritides: principles of rehabilitation].
AB  - Spondyloarthritides (SpA) cover the group of heterogeneous inflammatory rheumatic
      diseases, being chronic by duration and progressive by development, including
      ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Although it is a
      question of clinically different entities, this big group of rheumatic diseases
      has got numerous common clinical, functional, radiological and genetic features
      which make them different from the other inflammatory rheumatic diseases. One of
      the most important approaches to the treatment of SpA patients is medical
      rehabilitation and monitoring their functional status, as these diseases are
      followed by notable functional seizures on axial skeleton and affected joints,
      resulting in significant disabled conditions related to activities of daily
      living, quality of life and professional activities. Although in all valid and
      accepted recommendations for treatment of SpA, among which AS and PsA are most
      frequent, there is obligation to apply rehabilitation treatments (as a form of
      non pharmacological treatment) and everyday experiences testifies to that to
      large degree, but in medical literature there are few actual and precise data of
      such a treatment. Meta-analyses and observation studies, evaluating the results
      of scarce randomized controlled studies, mention the application
      ofkinesitherapeutic procedures, hydrotherapy and bath therapy in the process of
      treatment and rehabilitation of SpA patients, but their results don't have enough
      credibility for explanation and acceptance of such outcomes. In conclusion,
      medical rehabilitation which is most frequently based on kinesitherapeutic
      models, has to be an integral part of non pharmacological treatment of SpA,
      including all other procedures of physical therapy (ultrasound, cryotherapy,
      electrotherapy, laser) which have symptomatic effect and significantly complete
      useful impact of medical gymnastic, having major effects on the increase of
      functional capacity, with the obligation of more frequent, scientifically
      established monitoring and evaluation of non pharmacological treatment effect.

PMID- 21875004
TI  - [The International Classification of Functioning, Disability and Health (ICF) and
      rheumatic diseases].
AB  - Assessment of the impact of the rheumatic disease on the individual patient is
      necessary to evaluate the outcome of an intervention targeted at the disease
      process as well as at the restoration of the patient's functioning. The
      International Classification of Functioning, Disability and Health (ICF) is a
      comprehensive tool designed to record and organise a wide range of information
      about health and health related states, based on bio-psycho-social perspective.
      The ICF components, namely, body functions, body structures, and activities and
      participation are complemented by the contextual components, environmental
      factors and personal factors. All of them are in mutual interactions. The ICF
      contains lists of so-called ICF categories that describe the components of the
      integrative World Health Organisation model. It uses an alphanumerical model
      where categories are 'nested' so that broader categories are defined to include
      more detailed subcategories of the parent categories. Organized in such a way and
      with more than 1400 categories ICF covers virtually all the spectrum of problems
      encountered in patients with musculoskeletal conditions. The main practical tools
      of the ICF include ICF check lists, ICF core sets, ICF categorical profile and
      ICF assessment sheet. The ICF is likely to become the generally accepted
      conceptual framework and will be increasingly used in clinical practice to
      structure patient problems, particularly in multidisciplinary care and for
      rehabilitation purposes.

PMID- 21875005
TI  - [Ultrasonography in locomotor system diseases].
AB  - Ultrasonography and Doppler sonography have a significant role in detecting
      structural changes of joints and soft tissues, in clinical follow-up and
      evaluation of therapy. Ultrasonography is sensitive, available, inexpensive
      method, as well as the method without ionization effects. It is method that has a
      high sensitivity when compared with conventional radiography. It clearly
      demonstrates joint and soft tissue abnormalities and may be recommended in early
      evaluation, monitoring of response to therapy and disease activity monitoring. In
      some patients ultrasonographic findings suggest application of the other imaging
      modalities and diagnostic procedures. Ultrasound should be the part of a teamwork
      of experienced radiologist, physiatrics, and rheumatologist. It implies adequate
      equipment, defined site of examination based on clinical exam.

PMID- 21875006
TI  - [Standardised ultrasound scanning of the shoulder--normal and basic pathological
      findings].
AB  - Diagnostic ultrasound (US) is noninvasive, non-ionisating and cost-effective
      imaging diagnostic technique. It has emerged as a useful imaging modality for the
      diagnosis of joint and soft tissue pathology. The shoulder is probably the most
      frequently analyzed joint. Diagnostic US can be considered as an extension of
      physical examination and has better sensitivity and specificity for the detection
      of rotator cuff tendon tear compared to the physical examination. A high
      frequency linear probe (7.5-15 MHz) with high resolution transducer should be
      used. US investigation of the shoulder includes scanning of the long head of the
      biceps, the subskapularis, the supraspinatus, and the infraspinatus tendon in
      longitudinal and transverse planes, and scanning of the subacromial-subdeltoid
      (SA/SD) bursa, glenohumeral (GH) and acromioclavicular (AC)joint. The most
      frequent US findings of the shoulder are effusion in the long head of the biceps
      tendon, and in the SA/SD bursa, tendinosis or tear of the supraspinatus tendon,
      and the degenerative changes of the AC joint. In inflammatory arthopahies
      synovial effusion and hypertrophy of the GH joint can be evaluated. Power Doppler
      sonography is used for detection of sinovial vascularisation. In this paper
      standardized techinque for the US examination of the shoulder is described.
      Pictures of normal and sam basic phathological findings are presented.

PMID- 21875007
TI  - [Standardised ultrasound scanning of the elbow].
AB  - Musculoskeletal ultrasound (US) is noninvasive, nonionisating and cost-effective
      imaging diagnostic technique. It is a useful imaging modality for the diagnosis
      of joint and soft tissue pathology and can be considered as an extension of
      physical examination. Elbow is easily accessed due to its superficial position. A
      high resolution, multi-frequency (10-15 MHz) linear transducer should be used. US
      investigation of the elbow includes scanning of the anterior, medial, lateral and
      posterior part of the joint. Common flexor and extensor origin at the humearal
      epicondyles, triceps tendon, distal biceps tendon and ulnar nerve should be
      analised. The most frequent US finding of the elbow is lateral epicondylitis. In
      inflammatory arthropaties bursal distension and joint effusion are easily
      accessed by US. Power Doppler sonography is used for detection of sinovial
      vascularisation. In this paper standardized techinque for the US examination of
      the elbow is described. The normal ulrasound anatomy of the elbow is illustrated.

PMID- 21875008
TI  - [Diagnostic ultrasound of the small joints of the hands and feet: current status
      and role of ultrasound in early arthritis].
AB  - The small joints of the hands and feet play a central role in the diagnosis and
      classification of arthropathy. Ultrasound can be used to assess involvement in
      areas that are clinically occult. The aim of this article was to review the
      current status of ultrasound imaging of patients with rheumatological disorders
      of the hands and feet. There is increasing evidence that ultrasound detects
      synovitis that is silent to clinical examination. Detection and classification of
      synovitis and the early detection of bone erosions are important in clinical
      decision making. Ultrasound has many advantages over other imaging techniques
      with which it is compared, particularly magnetic resonance. The ability to carry
      out a rapid assessment of many widely spacedjoints, coupled with clinical
      correlation, the ability to move and stress musculoskeletal structures and the
      use of ultrasound to guide therapy accurately are principal amongst these. The
      use of colour flow Doppler studies provides a measure of neovascularisation
      within the synovial lining of joints and tendons, and within tendons themselves,
      that is not available with other imaging techniques. Disadvantages compared to
      MRI include small field of view, poor image presentation, and difficulty in
      demonstrating cartilage and deep joints in their entirety.

PMID- 21875009
TI  - [Ultrasonography of the hip, knee and ankle].
AB  - Hip ultrasonography (US), besides visualization of anatomic structures, provides
      precise puncture and aspiration of the joint content. The most often US findings
      in inflammatory rheumatic diseases are intra-articular effusion (pathologic
      finding>2 mm), hypertrophy ofsynovial membrane, cartilage damage and bone
      erosions. US characteristics ofosteoarthritis (OA) are small amount of effusion,
      lost of cartilage, osteophytes on the articular edges and possible mild
      hypertrophy of synovial membrane. Recently, US has been used in diagnostics of
      many knee disorders, including lesions of articular cartilage, tendons,
      ligaments, menisci, synovial joint and surrounding blood vessels and muscles. US
      could be used for measuring thickness of hyaline cartilage and for assessment of
      its integrity at the area of femoral condyles and intercondylar notch, but only
      if patients are enable to bend their knees. Numerous arthropathies that affect
      the knee could be evaluated by US too, so it is possible to document the presence
      of effusion, hypertrophy ofsynovial membrane, formation ofpannus, popliteal
      cysts, loose bodies, cartilage thinness and synovial plica. New technologic
      development of US diagnostics provides high-quality presentation of some smaller
      structures like ankle joint, calcaneal insertion of Achilles tendon and
      surrounding soft tissues. The most important achievement is demonstration
      ofpathologic changes of Achilles tendon within inflammatory and degenerative
      diseases.

PMID- 21875010
TI  - [Systemic sclerosis--introductory lecture].
AB  - The pathogenesis of systemic sclerosis (SSc) is complex and appears to involve
      endothelium, epithelium, fibroblasts and immunological mediators, resulting in
      dysregulated vascular remodelling and ultimately vasculopathy. Endothelial cell
      injury is an early and probably initiating event, but the precise aethyology
      remains unclear. Vascular damage and tissue fibrosis are widespread in SSc and
      largely account for the protean clinical manifestations and substantial morbidity
      and mortality. Current therapies are primarily immunomodulatory in nature.
      Effective therapy will require directly targeting the fibrotic process and will
      necessitate an improved understanding of the roles of individual cell types and
      their products in the development of fibrosis.

PMID- 21875011
TI  - [Incidence, prevalence and disease characteristics of systemic sclerosis in Split
      Dalmatia County].
AB  - Systemic sclerosis (SSc) is a clinically heterogeneous generalized disorder which
      affects the connective tissue of the skin and internal organs such as
      gastrointestinal tract, lungs, heart and kidneys. It is characterized by
      alterations of the microvasculature, disturbances of the immune system and by
      massive deposition of collagen. Our aim was to to estimate the incidence,
      prevalence and disease characteristics of SSc in Split-Dalmatia County which has
      a population of 463,676 Caucasian people. A census of SSc cases for the period
      2007-2009 was conducted using hospital records for case identification. Diagnoses
      were verified by medical record review. All patients were evaluated by the
      validated American College of Rheumatology criteria for SSc. The exact 95%
      confidence interval (CI) based on binomial distribution was created for the
      incidence and prevalence estimates. RESULTS: Based on 51 verified cases of SSc,
      prevalence was initially estimated to be 15.6 cases per 100,000 adults (95% CI
      11.8-19.4), with an annual incidence of 3.2 new cases per 100,000 adults per year
      (95% CI 0.5-4.1). The ratio of women to men was 5.2:1. The median age of patients
      was 55.1 yr. This study establishes baseline estimates of SSc occurrence and
      characteristics in a large Croatian cohort consisting of Causation people. These
      data should facilitate research regarding the role of geographic and
      environmental factors for this disease in comparison populations.

PMID- 21875012
TI  - [Heart involvement and pulmonary arterial hypertension in patients with systemic
      sclerosis].
AB  - In patients with systemic sclerosis heart involvement is often manifest,
      associated with poor prognosis and increased mortality. Cardiac involvement may
      be manifested by myocardial disease, arrhhythmias, conduction system
      disturbances, pericardial abnormalities and right heart failure, which develops
      as a complication of pulmonary arterial hypertension and significantly influences
      the disease progression. Pulmonary arterial hypertension is a severe and
      progressive disease with significant morbidity and mortality, being more often
      diagnosed. Diagnostic methods in evaluation of heart involvement as well as
      pulmonary arterial hypertension are presented. Today's treatment modalities are
      discussed.

PMID- 21875013
TI  - [Interstitial lung disease (ILD) in systemic sclerosis (SSc)].
AB  - Intersitial lung disease is a frequent complication of systemic sclerosis that
      often has a poor pognosis and together with pulmonary arterial hypertension are
      the most common cause of death in scleroderma patients. For detection and
      evaluation of interstitial lung disease, high-resolution CT and pulmorary
      functional tests are pivotal. The decision about whether to start treatment is
      often the most difficult challenge. Patients with short duration of systemic
      disease with recent deterioration in DCO are the candidates for immunosupressive
      therapy. Best current initial treatment is intravenous monthly cyclophosphamide
      together with low-dose oral glucocorticoids although azathioprine and
      mycophenolate mofetil are also widely used.

PMID- 21875014
TI  - [Scleroderma renal crisis].
AB  - Systemic sclerosis (SSc) is a multisystem disease whose clinical manifestations
      result from inflammation, vascular injury and obliteration, and cutaneous and
      visceral fibrosis. Scleroderma renal crisis (SRC) occurs in 5% of patients with
      particullary diffuse form of SSc. It is characterized by malignant hypertension
      and oligo/ anuric acute renal failure. SRC was once a uniformly fatal
      complication of SSc. The prognosis of SRC has significantly improved with the
      introduction of angiotensin-converting enzyme inhibitors (ACEi) as treatment. The
      treatment of SRC relies on tight control of blood pressure and aggressive
      treatment with ACEi, if needed in combination with other types of
      antihypertensive drugs.

PMID- 21875015
TI  - [Gastrointestinal changes in patients with systemic sclerosis].
AB  - Gastrointestinal changes in patients with systemic sclerosis are presented.

PMID- 21875016
TI  - [Digital ulcers in systemic sclerosis].
AB  - Digital ulcers occur in up to 50% of patients with limited or diffuse systemic
      sclerosis. The lesions are extremely painful leading to substantial functional
      disability, local infection susceptibility and can escalate to gangrene and
      amputation. Underlying vasculopathy and angiopathy cause obliteration of digital
      arteries and ischemic tissue changes. Management of digital ulcers includes non
      pharmacological and pharmacological modalities. Early diagnosis in preclinical
      phase would enable preventive treatment prior to irreversible changes.

PMID- 21875017
TI  - Clinical characteristics of scleroderma-like disorders.

PMID- 21875018
TI  - Capillaroscopy as a prognostic tool for the development of connective tissue
      disease in patients with Raynaud's phenomenon.

PMID- 21875019
TI  - [Why do we need registries of patients on biologics drugs?].
AB  - Significant data on applied biologic drugs can be found in national registries of
      treated patients. The main reason of establishing registries is monitoring the
      efficacy and safety of biologic drugs in long-term treatment. Registries provide
      information on outcome of the disease, life quality, and risk-benefit ratio
      including society costs.

PMID- 21875020
TI  - [Golimumab (Simponi)--first subcutaneous anti-TNF with once-monthly application].

PMID- 21875021
TI  - [Optimizing rheumatoid arthritis treatment with rituximab--individualized patient
      approach].
AB  - Disease activity assessment is a cornerstone of monitoring rheumatoid arthritis
      (RA) development and guidance for rituximab treatment. Beside clinical signs and
      symptoms biomarkers (RF and anti-CCP) are important early predictors of response
      to therapy and they can predict disease development. Autoantibody (RF and anti
      CCP) seropositivity has been associated with positive response to rituximab (RTX)
      in antiTNF-IR patients, DMARD-IR patients and MTX-naive patients. Selecting
      therapy for TNF-IR patients providing most likely response it should be taken in
      consideration results form recently published assessments demonstrating for RTX
      treated patients significant improvement in DAS28 from baseline versus
      alternative TNF inhibitor treatment. Recently published NICE treatment guideline
      is recommending upon antiTNF failure RTX treatment (in combination with MTX)
      instead antiTNF cycling.

PMID- 21875022
TI  - [Safety of rituximab in patients with rheumatoid arthritis].
AB  - RA is a chronic disease and long-term use of treatments that target TNF or B
      cells will be required for continued disease control. One approach to targeting B
      cells in RA is the use ofrituximab. It is a genetically engineered chimeric
      monoclonal antibody that selectively depletes peripheral B lymphocytes by binding
      CD20 on the cell surface. Long-term safety data show that rituximab treatment is
      associated with rates of infections and serious infections that remain stable
      over multiple treatment courses. Also, is associated with rates of malignancy
      consistent with data from the general RA population and is not associated with an
      increase in the rate of serious infections in patients who receive subsequent
      biologic treatment. In conclusion, rituximab is generally safe and well
      tolerated.

PMID- 21875023
TI  - [Treatment of rheumatoid and psoriatic arthritis--review of leflunomide].

PMID- 21875024
TI  - [Topical treatment with diclofenac with improved effect (Diclo Duo spray)].

PMID- 21875025
TI  - [Patients' opinions and knowledge about osteoporosis in Croatia].

PMID- 21875026
TI  - [Theodor Durrigl--laureate of the Croatian Academy of Medical Science in 2008].

PMID- 21875027
TI  - Paramagnetic relaxation enhancement (PRE) as a tool for probing diffusion in
      environmentally relevant porous media.
AB  - The transport diffusivity of the paramagnetic molecule 2,2,6,6
      tetramethylpiperidine-1-oxyl (TEMPO) was measured by monitoring its influence on
      the NMR transverse relaxation time (T2) on surrounding water protons - also known
      as paramagnetic relaxation enhancement (PRE). Due to the nature of the PRE
      effect, few paramagnetic molecules are able to simultaneously reduce the T2 of
      many NMR active nuclei, which represents a significant gain in sensitivity. In an
      aqueous solution, the minimal detectable TEMPO concentration was around 70 ppm.
      The value of the diffusivity was estimated by fitting the relaxation data,
      collected as a function of time, with the appropriate solutions of the second
      Fick's law in respect to the corresponding sample geometry and dimensions.
      Considering the experimentally determined TEMPO relaxivity in water ("TEMPO-water
      relaxivity"; R(TEMPO) = (1.05 +/- 0.12) * 10-3 ppm-1 s-1), the obtained diffusion
      coefficients (D) of TEMPO in homogeneous solution and in a water saturated sand
      column (D(bulk) = (6.7 +/- 0.4) * 10-10 m2 s-1 and D(sand) = (1.4 +/- 0.5) * 10
      10 m2 s-1, respectively) are in good agreement with the expected values
      (literature values: D(bulk) = 6.6 * 10-10 m2 s-1, 1.3 * 10-10 m2 s-1 < D(sand) <
      2.3 * 10-10 m2 s-1). This new approach enables one to determine the diffusivity
      of paramagnetic molecules in homogeneous (aqueous solution) and porous media with
      basic NMR equipment, at low concentrations and in a noninvasive manner.

PMID- 21875028
TI  - A single active-site mutation of P450BM-3 dramatically enhances substrate binding
      and rate of product formation.
AB  - Identifying key structural features of cytochromes P450 is critical in
      understanding the catalytic mechanism of these important drug-metabolizing
      enzymes. Cytochrome P450BM-3 (BM-3), a structural and mechanistic P450 model,
      catalyzes the regio- and stereoselective hydroxylation of fatty acids. Recent
      work has demonstrated the importance of water in the mechanism of BM-3, and site
      specific mutagenesis has helped to elucidate mechanisms of substrate recognition,
      binding, and product formation. One of the amino acids identified as playing a
      key role in the active site of BM-3 is alanine 328, which is located in the loop
      between the K helix and beta 1-4. In the A328V BM-3 mutant, substrate affinity
      increases 5-10-fold and the turnover number increases 2-8-fold compared to wild
      type enzyme. Unlike wild-type enzyme, this mutant is purified from E. coli with
      endogenous substrate bound due to the higher binding affinity. Close examination
      of the crystal structures of the substrate-bound native and A328V mutant BMPs
      indicates that the positioning of the substrate is essentially identical in the
      two forms of the enzyme, with the two valine methyl groups occupying voids
      present in the active site of the wild-type substrate-bound structure.

PMID- 21875029
TI  - Structures of bare and hydrated [Pb(aminoacid-H)]+ complexes using infrared
      multiple photon dissociation spectroscopy.
AB  - Infrared multiple-photon dissociation (IRMPD) spectroscopy was used to determine
      the gas-phase structures of deprotonated Pb(2+)/amino acid (Aa) complexes with
      and without a solvent molecule present. Five amino acid complexes with side
      chains containing only carbon and hydrogen (Ala, Val, Leu, Ile, Pro) and one with
      a basic side chain (Lys) were compared. These experiments demonstrated that all
      [Pb(Aa-H)](+) complexes have Pb(2+) covalently bound between the amine nitrogen
      and carbonyl oxygen. The nonhydrated complexes containing Ala, Val, Leu, Ile, and
      Pro are amine-deprotonated, whereas the one containing Lys is deprotonated at its
      carboxylic acid. The difference is attributed to the polar and basic side chain
      of lysine, which helps stabilize Pb(2+). IRMPD spectroscopy was also performed on
      the monohydrated analogues of the [Pb(Aa-H)](+) complexes. The [Pb(Aa-H)H(2)O](+)
      complexes, where Aa = Ala, Val, Leu, and Ile, exhibited two N-H stretches as well
      as a carboxylic acid O-H and a PbO-H stretch. Hence, their structures are
      monohydrated versions of the amine-deprotonated [Pb(Aa-H)](+) complexes where a
      proton transfer has occurred from the lead-bound water to the deprotonated amine.
      The IRMPD spectrum and calculations suggest that [Pb(Pro-H)H(2)O](+) has a
      hydrated carboxylate salt structure. The structure of [Pb(Lys-H)H(2)O](+) was
      also carboxyl-deprotonated, but Pb(2+) is bound to the carbonyl oxygen and the
      amine nitrogen, with one of the protons belonging to the water transferred to the
      basic side chain. This results in an intramolecular hydrogen bond that does not
      absorb in the region of the spectrum probed in these experiments. The IRMPD
      spectra and structural characterizations were confirmed and aided by infrared
      spectra calculated at the B3LYP/6-31+G(d,p) level of theory and 298 K enthalpies
      and Gibbs energies using the MP2(full)/6-311++G(2d,2p) method on the B3LYP
      geometries.

PMID- 21875031
TI  - Gravitational settling effects on unit cell predictions of colloidal retention in
      porous media in the absence of energy barriers.
AB  - Laboratory column experiments for colloidal transport and retention are often
      carried out with flow direction oriented against gravity (up-flow) to minimize
      retention of trapped air. However, the models that underlie colloidal filtration
      theory (e.g., unit cell models such as the Happel sphere-in-cell and hemispheres
      in-cell) typically set flow in the same direction as gravity (down-flow). We
      performed unit model simulations and experimental observations of retention of
      colloids with different size and density in porous media in the absence of energy
      barriers under both up-flow and down-flow conditions. Unit cell models predicted
      very different deposition (e.g., for large or dense colloids with gravity number
      N(G) > 0.01 at pore water velocity of 4 m/day) under down-flow versus up-flow
      conditions, which reflect underlying influences of gravity and flow on simulated
      colloid trajectories that resulted in very different distributions of attached
      colloids over the model surfaces. The Happel sphere-in-cell model showed greater
      sensitivity to flow orientation relative to gravity than the hemispheres-in-cell
      model. In contrast, experimental results were relatively insensitive to
      orientation of flow with respect to gravity, as a result of the variety of
      orientations of flow relative to gravity and to the porous media surface that
      exist in actual porous media. Notably, the down-flow simulations corresponded
      most closely to the experimental results (for near neutrally buoyant colloids);
      which justifies the common practice of comparing up-flow experiments to
      theoretical predictions developed for down-flow conditions.

PMID- 21875032
TI  - Synthesis and self-assembly of well-defined poly(amino acid) end-capped
      poly(ethylene glycol) and poly(2-methyl-2-oxazoline).
AB  - Poly(ethylene glycol) (PEG) and poly(2-methyl-2-oxazoline) (PMOx) are water
      soluble, biocompatible polymers with stealth hemolytic activities. Poly(amino
      acid) (PAA) end-capped PEG and PMOx were prepared using amino-terminated
      derivatives of PEG and PMOx as macroinitiators for the ring-opening
      polymerization of gamma-benzyl protected l-glutamate N-carboxyanhydride and S
      benzyloxycarbonyl protected l-cysteine N-carboxyanhydride, respectively, in the
      presence of urea, at room temperature. The molecular weight of the PAA moiety was
      kept between M(n) = 2200 and 3000 g mol(-1). PMOx was polymerized by cationic
      ring-opening polymerization resulting in molecular weights of M(n) = 5000 and
      10,000 g mol(-1), and PEG was a commercial product with M(n) = 5000 g mol(-1).
      Here, we investigate the self-assembly of the resulting amphiphilic block
      copolymers in water and the effect of the chemical structure of the block
      copolymers on the solution properties of self-assembled nanostructures. The PEG
      block-poly(amino acid), PEG-b-PAA, and PMOx-block-poly(amino acid), PMOx-b-PAA,
      block copolymers have a narrow and monomodal molecular weight distribution (PDI <
      1.3). Their self-assembly in water was studied by dynamic light scattering and
      fluorescence spectroscopy. In aqueous solution, the block copolymers associate
      into particles with hydrodynamic radii (R(H)) ranging in size from R(H) 70 to 130
      nm, depending on the block copolymer architecture and the polymer molecular
      weight. Larger R(H) and critical association concentration values were obtained
      for copolymers containing poly(S-benzyloxycarbonyl-l-cysteine) compared to their
      poly(gamma-benzyl-L-glutamate) analogue. FTIR investigations revealed that the
      poly(gamma-benzyl-L-glutamate) block adopts a helical conformation, while the
      poly(S-benzyloxycarbonyl-L-cysteine) block exists as beta-sheet.

PMID- 21875033
TI  - Growth of piezoelectric water-free GeO2 and SiO2-substituted GeO2 single
      crystals.
AB  - Using the slow-cooling method in selected fluxes, we have grown spontaneously
      nucleated single-crystals of pure GeO(2) and SiO(2)-substituted GeO(2) materials
      with the alpha-quartz structure. These piezoelectric materials were obtained in
      millimeter size as well-faceted, visually colorless, and transparent crystals.
      Cubic-like or hexagonal prism-like morphology was identified depending on the
      chemical composition of the single-crystals and on the nature of the flux. Both
      the silicon substitution rate and the homogeneity of its distribution were
      estimated by Energy Dispersive X-ray spectroscopy. The cell parameters of the
      flux-grown GeO(2) and Ge(1-x)Si(x)O(2) (0.038 <= x <= 0.089) solid-solution were
      deduced from their X-ray powder diffraction pattern. As expected, the cell
      volumes decrease as the silicon content substitution increases. A room
      temperature Infrared spectroscopy study confirms the absence of hydroxyl groups
      in the as-grown crystals. Unlike what was observed for hydrothermally grown
      GeO(2) crystals, these flux-grown oxide materials did not present any phase
      transition before melting as pointed out by a Differential Scanning Calorimetry
      study. Neither a alpha-quartz/beta-quartz transition as encountered in SiO(2)
      near 573  degrees C nor a alpha-quartz to rutile transformation were detected for
      these GeO(2) and Ge(1-x)Si(x)O(2) single-crystals.

PMID- 21875030
TI  - Discovery of carboxyethylpyrroles (CEPs): critical insights into AMD, autism,
      cancer, and wound healing from basic research on the chemistry of oxidized
      phospholipids.
AB  - Basic research, exploring the hypothesis that 2-(omega-carboxyethyl)pyrrole (CEP)
      modifications of proteins are generated nonenzymatically in vivo is delivering a
      bonanza of molecular mechanistic insights into age-related macular degeneration,
      autism, cancer, and wound healing. CEPs are produced through covalent
      modification of protein lysyl epsilon-amino groups by gamma-hydroxyalkenal
      phospholipids that are formed by oxidative cleavage of docosahexaenate-containing
      phospholipids. Chemical synthesis of CEP-modified proteins and the production of
      highly specific antibodies that recognize them preceded and facilitated their
      detection in vivo and enabled exploration of their biological occurrence and
      activities. This investigational approach, from the chemistry of biomolecules to
      disease phenotype, is proving to be remarkably productive.

PMID- 21875034
TI  - An unfractionated fucoidan from Ascophyllum nodosum: extraction,
      characterization, and apoptotic effects in vitro.
AB  - An unfractionated fucoidan was extracted from the brown alga Ascophyllum nodosum.
      Extraction of fucoidan from seaweed was carried out using an innovative low
      chemical process. A combinational approach involving compositional analysis,
      HPAEC, IR analysis, GPC, and NMR was employed to elucidate the composition and
      structure of an unfractionated fucoidan from A. nodosum. This fucoidan is
      composed mainly of fucose (52.1%), and also galactose (6.1%), glucose (21.3%),
      and xylose (16.5%). Sulfate content was determined to be 19%. GPC data indicated
      a polydisperse fucoidan containing two main size fractions (47 and 420 kDa). NMR
      analyses revealed a fucoidan displaying broad, complex signals as expected for
      such a high molecular weight and heterogeneous polymer with resonances consistent
      with a fucoidan isolated previously from A. nodosum. The effects of fucoidan on
      the apoptosis of human colon carcinoma cells and fucoidan-mediated signaling
      pathways were also investigated. Fucoidan decreased cell viability and induced
      apoptosis of HCT116 colon carcinoma cells. Fucoidan treatment of HCT116 cells
      induced activation of caspases-9 and -3 and the cleavage of PARP, led to
      apoptotic morphological changes, and altered mitochondrial membrane permeability.
      These results detail the structure and biological activity of an unfractionated
      fucoidan from A. nodosum.

PMID- 21875035
TI  - Application of nanosecond-UV laser ablation-inductively coupled plasma mass
      spectrometry for the isotopic analysis of single submicrometer-size uranium
      particles.
AB  - For the first time, laser ablation-inductively coupled plasma mass spectrometry
      (LA-ICPMS) was used to carry out isotopic measurement on single submicrometer
      size uranium particles. The analytical procedure was applied on two particle
      containing samples already analyzed in the same laboratory by established
      techniques for particle analysis: combination of the fission track technique with
      thermo-ionization mass spectrometry (FT-TIMS) and secondary ion mass spectrometry
      (SIMS). Particles were extracted from their initial matrix with ethanol and
      deposited on a polycarbonate disk where they were fixed in a layer of an organic
      compound (collodion). Prior to the isotopic analysis, particles were precisely
      located on the disk's surface by scanning electron microscopy (SEM) for one
      sample and using the fission track technique for the other sample. Most of the
      particles were smaller than 1 MUm, and their (235)U content was in the femtogram
      range. (235)U/(238)U ratios were successfully analyzed for all located particles
      using a nanosecond-UV laser (Cetac LSX 213 nm) coupled to a quadrupole-based
      ICPMS (Thermo "X-Series II"). LA-ICPMS results, although less precise and
      accurate (typically 10%) than the ones obtained by FT-TIMS and SIMS due to short
      (20-40 s), transient, and noisy signals, are in good agreement with the certified
      values or with the results obtained with other techniques. Thanks to good
      measurement efficiency (~6 * 10(-4)) and high signal/noise ratio during the
      analysis, LA-ICPMS can be considered a very promising technique for fast particle
      analysis, provided that uranium-bearing particles are fixed on the sample holder
      and located prior to isotope measurement.

PMID- 21875036
TI  - Tricomponent catalytic alpha,alpha-difluorination of acid chlorides.
AB  - The selective alpha,alpha-difluorination of carbonyl compounds remains a
      challenge in modern organic synthesis; current methods often incorporate stepwise
      processes and/or harsh conditions, providing unsatisfactory mixtures of mono- and
      difluorinated products. In this communication, a practical, mild, and one-pot
      method for the selective alpha,alpha-difluorination of readily available acid
      chlorides is reported in which three separate catalysts act synergistically to
      form products in outstanding selectivity and fair to excellent yields.

PMID- 21875037
TI  - New reactivity of oxaziridine: Pd(II)-catalyzed aromatic C-H ethoxycarbonylation
      via C-C bond cleavage.
AB  - A novel Pd(II)-catalyzed aromatic C-H ethoxycarbonylation with oxaziridine
      involving C-C bond cleavage is described. Various aromatic 2-phenylpyridines and
      related compounds as well as aryl ureas can be effectively ethoxycarbonylated. A
      catalytic cycle involving Pd(II) and Pd(IV) is proposed.

PMID- 21875038
TI  - Direct C2-alkylation of azoles with alcohols and ethers through dehydrogenative
      cross-coupling under metal-free conditions.
AB  - A metal-free novel, simple, and highly efficient method for the direct C2
      alkylation of azoles with alcohols and ethers has been developed on the basis of
      an oxidative C-H activation process. The dehydrogenative C-C cross-coupling
      reactions of alpha-position sp(3) C-H in alcohols and ethers with the 2-position
      sp(2) C-H in azoles proceeded smoothly in the presence of tert-butyl
      hydroperoxide (TBHP) under neat reaction conditions, which generated the
      corresponding products in good yields.

PMID- 21875039
TI  - Kinetics and mechanism of alkaline decomposition of the pentathionate ion by the
      simultaneous tracking of different sulfur species by high-performance liquid
      chromatography.
AB  - Alkaline decomposition of pentathionate has been investigated by high-performance
      liquid chromatography, which allows us to track different sulfur-containing
      species simultaneously in the presence of a carbonate/hydrogen carbonate buffer
      at 25.0 +/- 0.1  degrees C and at a constant ionic strength. It has been shown
      that, besides the major product, thiosulfate, not only tetrathionate but also
      hexathionate appears in significant amounts during the course of the reaction. At
      higher pHs, both of them are unstable long-lived intermediates because of their
      well-known alkaline degradation, but a decrease of the pH increases their
      stability (especially that of tetrathionate), meaning that they may even become
      end products. On the basis of these observations, a 10-step kinetic model with
      five fitted and five fixed rate coefficients is suggested and discussed to take
      all of the most important characteristics of the decomposition into account. We
      have also demonstrated and discussed that the well-known thiosulfate-assisted
      rearrangement of pentathionate leading to hexathionate might only play a very
      minor role in the formation of hexathionate under our experimental conditions.

PMID- 21875040
TI  - Multiple structures and dynamics of [CpRu(CO)2]2 and [CpFe(CO)2]2 in solution
      revealed with two-dimensional infrared spectroscopy.
AB  - Two-dimensional infrared (2DIR) spectroscopy is applied to both
      (Cp)(2)Fe(2)(CO)(4) and its ruthenium analog (Cp)(2)Ru(2)(CO)(4) in order to
      study the vibrational dynamics of these two systems. Combining the results of
      2DIR spectroscopy and DFT calculations, the different structural forms of both
      the iron and the ruthenium complexes were characterized, furthering the previous
      assignment of the linear IR spectrum by determining the transition frequencies
      associated with the different isomeric forms. Monitoring the time-dependent
      amplitudes of the cross peaks enabled the observation of equilibrium energy
      transfer dynamics between different vibrational modes of the cis-B
      (Cp)(2)Fe(2)(CO)(4) and the gauche-NB (Cp)(2)Ru(2)(CO)(4) complexes. Treating the
      energy transfer as an equilibrium process, we extracted the rate constants
      associated with both the uphill and the downhill transfer of vibrational energy,
      finding that the difference in the rate constants of the two metal complexes maps
      to the difference in the energy gap between the two modes involved.

PMID- 21875042
TI  - Geometric and electronic structures of peroxomanganese(III) complexes supported
      by pentadentate amino-pyridine and -imidazole ligands.
AB  - Three peroxomanganese(III) complexes [Mn(III)(O(2))(mL(5)(2))](+),
      [Mn(III)(O(2))(imL(5)(2))](+), and [Mn(III)(O(2))(N4py)](+) supported by
      pentadentate ligands (mL(5)(2) = N-methyl-N,N',N'-tris(2-pyridylmethyl)ethane-1,2
      diamine, imL(5)(2) = N-methyl-N,N',N'-tris((1-methyl-4-imidazolyl)methyl)ethane
      1,2-diamine, and N4py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine)
      were generated by treating Mn(II) precursors with H(2)O(2) or KO(2). Electronic
      absorption, magnetic circular dichroism (MCD), and variable-temperature, variable
      field MCD data demonstrate that these complexes have very similar electronic
      transition energies and ground-state zero-field splitting parameters, indicative
      of nearly identical coordination geometries. Because of uncertainty in peroxo
      (side-on eta(2) versus end-on eta(1)) and ligand (pentadentate versus
      tetradentate) binding modes, density functional theory (DFT) computations were
      used to distinguish between three possible structures: pentadentate ligand
      binding with (i) a side-on peroxo and (ii) an end-on peroxo, and (iii)
      tetradentate ligand binding with a side-on peroxo. Regardless of the supporting
      ligand, isomers with a side-on peroxo and the supporting ligand bound in a
      tetradentate fashion were identified as most stable by >20 kcal/mol.
      Spectroscopic parameters computed by time-dependent (TD) DFT and multireference
      SORCI methods provided validation of these isomers on the basis of experimental
      data. Hexacoordination is thus strongly preferred for peroxomanganese(III)
      adducts, and dissociation of a pyridine (mL(5)(2) and N4py) or imidazole
      (imL(5)(2)) arm is thermodynamically favored. In contrast, DFT computations for
      models of [Fe(III)(O(2))(mL(5)(2))](+) demonstrate that pyridine dissociation is
      not favorable; instead a seven-coordinate ferric center is preferred. These
      different results are attributed to the electronic configurations of the metal
      centers (high spin d(5) and d(4) for Fe(III) and Mn(III), respectively), which
      results in population of a metal-peroxo sigma-antibonding molecular orbital and,
      consequently, longer M-O(peroxo) bonds for peroxoiron(III) species.

PMID- 21875041
TI  - Multinuclear cytotoxic metallodrugs: physicochemical characterization and
      biological properties of novel heteronuclear gold-titanium complexes.
AB  - An unprecedented series of titanocene-gold bi- and trimetallic complexes of the
      general formula [[(eta(5)-C(5)H(5))(MU-eta(5):kappa(1)
      C(5)H(4)(CH(2))(n)PPh(2))TiCl(2)](m)AuCl(x)](q+) (n = 0, 2, or 4; m = 1, x = 1, q
      = 0 or m = 2, x = 0, q = 1) have been prepared and characterized
      spectroscopically. The luminescence spectroscopy and photophysics of one of the
      compounds, [[(eta(5)-C(5)H(5))(MU-eta(5):kappa(1)
      C(5)H(4)PPh(2))TiCl(2)](2)Au]PF(6), have been investigated in 2MeTHF solution and
      in the solid state at 77 and 298 K. Evidence for interfragment interactions based
      on the comparison of electronic band positions and emission lifetimes, namely,
      triplet energy transfer (ET) from the Au- to the Ti-containing chromophores, is
      provided. The cytotoxicity of the complexes was evaluated on A2780 ovarian cancer
      cells and on their cisplatin-resistant cell line A2780cisR; the compounds showed
      activity in the low micromolar range that was markedly more active than the
      corresponding titanocene-phosphine precursors [(eta(5)-C(5)H(5))(eta(5)
      C(5)H(4)(CH(2))(n)PPh(2))TiCl(2)], cisplatin, and, for some of them, the gold
      analogue [(PPh(3))AuCl]. In an attempt to draw preliminary structure-activity
      relationships, cell uptake measurements and interaction studies with plasmid DNA
      and the model protein ubiquitin (Ub) have been undertaken on some of the
      compounds.

PMID- 21875043
TI  - Absorption and fluorescence spectroscopy of growing ZnO quantum dots: size and
      band gap correlation and evidence of mobile trap states.
AB  - ZnO nanoparticles constitute a convenient model system for fundamental studies
      with many possible technical applications in, for example, sensors and the field
      of catalysis and optoelectronics. A large set of ZnO quantum dots in the size
      range 2.5-7 nm have been synthesized and analyzed in detail. Time resolved in
      situ UV-vis absorption measurements were used to monitor the growth of these
      particles in solution by correlating the optical band gap to particle size given
      from X-ray diffraction (XRD) measurements. The particles formed were isotropic in
      shape, but small initial deviations gave indications of a transition from
      thermodynamic to kinetically controlled growth for particles around 4 nm in
      diameter. On the basis of this, the behavior and mechanisms for the particle
      growth are discussed. The fluorescence dependence on particle size was
      investigated by combining fluorescence and UV-vis measurements on growing
      particles. This revealed that the positions of the fluorescence trap states are
      mobile toward the conduction- and valence band. A broadening of the trap states
      was also found, and a surface dependent mechanism of the trap state shift and
      broadening is proposed.

PMID- 21875045
TI  - Visualization of chlorine evolution at dimensionally stable anodes by means of
      scanning electrochemical microscopy.
AB  - Scanning electrochemical microscopy (SECM) has been used to detect and visualize
      the local electrocatalytic activity of dimensionally stable anodes (DSA) for
      Cl(2) evolution from brine. The sample generation-tip collection (SG-TC) mode of
      SECM shows limitations arising from complications connected with the reduction of
      Cl(2) at the SECM tip due to the presence of a significant amount of nondissolved
      Cl(2) gas. Because only dissolved Cl(2) can be electrochemically reduced at the
      tip, a large amount of the Cl(2) gas which is produced at active spots of the DSA
      is not detected. Additionally, a decrease of the cathodic current at the tip may
      occur owing to the adhesion of gas bubbles and blocking of the electrode surface.
      To overcome this limitation, the redox competition mode of SECM was extended and
      applied to the local visualization of Cl(2) evolution from highly concentrated
      brine solutions. High concentrations of Cl(2) produced at the sample can cause
      inhibition of the same reaction at the tip by accumulation of Cl(2) in the
      proximity of the SECM tip. In this way the tip current is decreased, which can be
      used as a measure for the catalytic activity of the sample underneath the tip.

PMID- 21875044
TI  - Control of interface nanoscale structure created by plasma-enhanced chemical
      vapor deposition.
AB  - Tailoring the structure of films deposited by plasma-enhanced chemical vapor
      deposition (PECVD) to specific applications requires a depth-resolved
      understanding of how the interface structures in such films are impacted by
      variations in deposition parameters such as feed position and plasma power.
      Analysis of complementary X-ray and neutron reflectivity (XR, NR) data provide a
      rich picture of changes in structure with feed position and plasma power, with
      those changes resolved on the nanoscale. For plasma-polymerized
      octafluorocyclobutane (PP-OFCB) films, a region of distinct chemical composition
      and lower cross-link density is found at the substrate interface for the range of
      processing conditions studied and a surface layer of lower cross-link density
      also appears when plasma power exceeds 40 W. Varying the distance of the feed
      from the plasma impacts the degree of cross-linking in the film center, thickness
      of the surface layer, and thickness of the transition region at the substrate.
      Deposition at the highest power, 65 W, both enhances cross-linking and creates
      loose fragments with fluorine content higher than the average. The thickness of
      the low cross-link density region at the air interface plays an important role in
      determining the width of the interface built with a layer subsequently deposited
      atop the first.

PMID- 21875046
TI  - 5-deoxyflavones with cytotoxic activity from Mimosa diplotricha.
AB  - Bioassay-guided isolation of Mimosa diplotricha led to the isolation of four new
      5-deoxyflavones, diplotrins A-C (1-3) and diplotasin (4), together with 12 known
      flavonoids, flavonolignans, and triterpenoids. On the basis of spectroscopic
      evidence, compounds 1-4 were characterized as 2',5'-dihydroxy-3,7,8,4'
      tetramethoxyflavone (1), 3'-hydroxy-3,7,8,4'-tetramethoxyflavone (2), 2'-hydroxy
      7,4',5'-trimethoxyflavone (3), and 4-hydroxy-3,10,11-trimethoxyisochromeno-[4,3
      b]-chromen-7(5H)-one (4). The cytotoxic effects of these isolated compounds were
      evaluated against the A549, AGS, HT-29, and PC3 human cancer cell lines.
      Compounds 2 and 5"-methoxyhydnocarpin-D (5) showed the most potent
      antiproliferative activity.

PMID- 21875047
TI  - Photophysical properties and electronic structure of stable, tunable synthetic
      bacteriochlorins: extending the features of native photosynthetic pigments.
AB  - Bacteriochlorins, which are tetrapyrrole macrocycles with two reduced pyrrole
      rings, are Nature's near-infrared (NIR) absorbers (700-900 nm). The strong
      absorption in the NIR region renders bacteriochlorins excellent candidates for a
      variety of applications including solar light harvesting, flow cytometry,
      molecular imaging, and photodynamic therapy. Natural bacteriochlorins are
      inherently unstable due to oxidative conversion to the chlorin (one reduced
      pyrrole ring) or the porphyrin. The natural pigments are also only modestly
      amenable to synthetic manipulation, owing to a nearly full complement of
      substituents on the macrocycle. Recently, a new synthetic methodology has
      afforded access to stable synthetic bacteriochlorins wherein a wide variety of
      substituents can be appended to the macrocycle at preselected locations. Herein,
      the spectroscopic and photophysical properties of 33 synthetic bacteriochlorins
      are investigated. The NIR absorption bands of the chromophores range from ~700 to
      ~820 nm; the lifetimes of the lowest excited singlet state range from ~2 to ~6
      ns; the fluorescence quantum yields range from ~0.05 to ~0.25; and the yield of
      the lowest triplet excited state is ~0.5. The spectroscopic/photophysical studies
      of the bacteriochlorins are accompanied by density functional theory (DFT)
      calculations that probe the characteristics of the frontier molecular orbitals.
      The DFT calculations indicate that the impact of substituents on the spectral
      properties of the molecules derives primarily from effects on the lowest
      unoccupied molecular orbital. Collectively, the studies show how the palette of
      synthetic bacteriochlorins extends the properties of the native photosynthetic
      pigments (bacteriochlorophylls). The studies have also elucidated design
      principles for tuning the spectral and photophysical characteristics as required
      for a wide variety of photochemical applications.

PMID- 21875048
TI  - Lewis acid-promoted addition of 1,3-bis(silyl)propenes to aldehydes: a route to
      1,3-dienes.
AB  - The Lewis acid-promoted addition of 1,3-bis(silyl)propenes to aldehydes to
      provide the corresponding (E)-1,3-dienes in excellent stereoselectivity and good
      to excellent yields is reported. The procedure is mild, base-free, and
      operationally straightforward.

PMID- 21875049
TI  - Synthesis and characterization of tris(heteroleptic) Ru(II) complexes bearing
      styryl subunits.
AB  - We have developed and optimized a well-controlled and refined methodology for the
      synthesis of substituted pi-conjugated 4,4'-styryl-2,2'-bipyridine ligands and
      also adapted the tris(heteroleptic) synthetic approach developed by Mann and co
      workers to produce two new representative Ru(II)-based complexes bearing the
      metal oxide surface-anchoring precursor 4,4'-bis[E-(p-methylcarboxy-styryl)]-2,2'
      bipyridine. The two targeted Ru(II) complexes, (4,4'-dimethyl-2,2'
      bipyridine)(4,4'-di-tert-butyl-2,2'-bipyridine)(4,4'-bis[E-(p-methylcarboxy
      styryl)]-2,2'-bipyridine) ruthenium(II) hexafluorophosphate, [Ru(dmbpy)(dtbbpy)(p
      COOMe-styryl-bpy)](PF(6))(2) (1) and (4,4'-dimethyl-2,2'-bipyridine)(4,4'-dinonyl
      2,2'-bipyridine)(4,4'-bis[E-(p-methylcarboxy-styryl)]-2,2'-bipyridine)
      ruthenium(II) hexafluorophosphate, [Ru(dmbpy)(dnbpy)(p-COOMe-styryl
      bpy)](PF(6))(2) (2) were obtained as analytically pure compounds in high overall
      yields (>50% after 5 steps) and were isolated without significant purification
      effort. In these tris(heteroleptic) molecules, NMR-based structural
      characterization became nontrivial as the coordinated ligand sets each sense
      profoundly distinct magnetic environments greatly complicating traditional 1D
      spectra. However, rational two-dimensional approaches based on both homo- and
      heteronuclear couplings were readily applied to these structures producing quite
      definitive analytical characterization and the associated methodology is
      described in detail. Preliminary photoluminescence and photochemical
      characterization of 1 and 2 strongly suggests that both molecules are
      energetically and kinetically suitable to serve as sensitizers in energy-relevant
      applications.

PMID- 21875051
TI  - Ambient surfactantless synthesis, growth mechanism, and size-dependent
      electrocatalytic behavior of high-quality, single crystalline palladium
      nanowires.
AB  - In this report, we utilize the U-tube double diffusion device as a reliable,
      environmentally friendly method for the size-controlled synthesis of high
      quality, single crystalline Pd nanowires. The nanowires grown in 200 and 15 nm
      polycarbonate template pores maintain diameters of 270 +/- 45 nm and 45 +/- 9 nm,
      respectively, and could be isolated either as individual nanowires or as ordered
      free-standing arrays. The growth mechanism of these nanowires has been
      extensively explored, and we have carried out characterization of the isolated
      nanowires, free-standing nanowire arrays, and cross sections of the filled
      template in order to determine that a unique two-step growth process predominates
      within the template pores. Moreover, as-prepared submicrometer and nanosized
      wires were studied by comparison with ultrathin 2 nm Pd nanowires in order to
      elucidate the size-dependent trend in oxygen reduction reaction (ORR)
      electrocatalysis. Subsequently, the desired platinum monolayer overcoating was
      reliably deposited onto the surface of the Pd nanowires by Cu underpotential
      deposition (UPD) followed by galvanic displacement of the Cu adatoms. The
      specific and platinum mass activity of the core-shell catalysts was found to
      increase from 0.40 mA/cm(2) and 1.01 A/mg to 0.74 mA/cm(2) and 1.74 A/mg as the
      diameter was decreased from the submicrometer size regime to the ultrathin
      nanometer range.

PMID- 21875050
TI  - Thermodynamic, kinetic, and mechanistic study of oxygen atom transfer from
      mesityl nitrile oxide to phosphines and to a terminal metal phosphido complex.
AB  - The enthalpies of oxygen atom transfer (OAT) from mesityl nitrile oxide (MesCNO)
      to Me(3)P, Cy(3)P, Ph(3)P, and the complex (Ar[(t)Bu]N)(3)MoP (Ar = 3,5
      C(6)H(3)Me(2)) have been measured by solution calorimetry yielding the following
      P-O bond dissociation enthalpy estimates in toluene solution (+/-3 kcal mol(-1)):
      Me(3)PO [138.5], Cy(3)PO [137.6], Ph(3)PO [132.2], (Ar[(t)Bu]N)(3)MoPO [108.9].
      The data for (Ar[(t)Bu]N)(3)MoPO yield an estimate of 60.2 kcal mol(-1) for
      dissociation of PO from (Ar[(t)Bu]N)(3)MoPO. The mechanism of OAT from MesCNO to
      R(3)P and (Ar[(t)Bu]N)(3)MoP has been investigated by UV-vis and FTIR kinetic
      studies as well as computationally. Reactivity of R(3)P and (Ar[(t)Bu]N)(3)MoP
      with MesCNO is proposed to occur by nucleophilic attack by the lone pair of
      electrons on the phosphine or phosphide to the electrophilic C atom of MesCNO
      forming an adduct rather than direct attack at the terminal O. This mechanism is
      supported by computational studies. In addition, reaction of the N-heterocyclic
      carbene SIPr (SIPr = 1,3-bis(diisopropyl)phenylimidazolin-2-ylidene) with MesCNO
      results in formation of a stable adduct in which the lone pair of the carbene
      attacks the C atom of MesCNO. The crystal structure of the blue SIPr.MesCNO
      adduct is reported, and resembles one of the computed structures for attack of
      the lone pair of electrons of Me(3)P on the C atom of MesCNO. Furthermore, this
      adduct in which the electrophilic C atom of MesCNO is blocked by coordination to
      the NHC does not undergo OAT with R(3)P. However, it does undergo rapid OAT with
      coordinatively unsaturated metal complexes such as (Ar[(t)Bu]N)(3)V since these
      proceed by attack of the unblocked terminal O site of the SIPr.MesCNO adduct
      rather than at the blocked C site. OAT from MesCNO to pyridine,
      tetrahydrothiophene, and (Ar[(t)Bu]N)(3)MoN was found not to proceed in spite of
      thermochemical favorability.

PMID- 21875052
TI  - Total synthesis of the marine metabolite (+/-)-polysiphenol via highly
      regioselective intramolecular oxidative coupling.
AB  - (+/-)-Polysiphenol (1), an atropisomerically stable 4,5-dibrominated 9,10
      dihydrophenanthrene from Polysiphonia ferulacea, was prepared by a biomimetically
      inspired highly regioselective intramolecular oxidative coupling of a
      dibrominated dihydrostilbene. The installation of the two bromine atoms prior to
      oxidative coupling prevents further oxidation to a planar aromatized
      phenanthrene. By this strategy, the synthesis of (+/-)-polysiphenol was achieved
      in four steps in 70% overall yield. Synthesis of the naturally occurring 5,5'
      (ethane-1,2-diyl)bis(3-bromobenzene-1,2-diol) (2) (the likely biogenetic
      precursor of polysiphenol) and 5,5'-(ethane-1,2-diyl)bis(3,4,6-tribromobenzene
      1,2-diol) (9) are also reported. The origins of the regioselectivity in the
      oxidative coupling are explored.

PMID- 21875053
TI  - Methanogens: principal methylators of mercury in lake periphyton.
AB  - Mercury methylation and demethylation rates were measured in periphyton biofilms
      growing on submerged plants from a shallow fluvial lake located along the St.
      Lawrence River (Quebec, Canada). Incubations were performed in situ within
      macrophytes beds using low-level spikes of (199)HgO and Me(200)Hg stable isotopes
      as tracers. To determine which microbial guilds are playing a role in these
      processes, methylation/demethylation experiments were performed in the absence
      and presence of different metabolic inhibitors: chloramphenicol (general
      bacteriostatic inhibitor), molybdate (sodium molybdate, a sulfate reduction
      inhibitor), BESA (2-bromoethane sulfonic acid, a methanogenesis inhibitor), and
      DCMU (3-(3,4-dichlorophenyl)-1,1 dimethyl urea, a photosynthesis inhibitor).
      Active microbes of the periphytic consortium were also characterized using 16S
      rRNA gene sequencing. Methylation rates in the absence of inhibitors varied from
      0.0015 to 0.0180 d(-1) while demethylation rates ranged from 0.083 to 0.217 d(
      1), which corresponds to a net methylmercury balance of -0.51 to 1.28 ng gDW
      periphyton(-1) d(-1). Methylation rates were significantly decreased by half by
      DCMU and chloramphenicol, totally inhibited by BESA, and were highly stimulated
      by molybdate. This suggests that methanogens rather than sulfate reducing
      bacteria were likely the primary methylators in the periphyton of a temperate
      fluvial lake, a conclusion supported by the detection of 16S rRNA gene sequences
      that were closely related to those of methanogens. This first clear demonstration
      of methanogens' role in mercury methylation in environmental periphyton samples
      expands the known diversity of microbial guilds that contribute to the formation
      of the neurotoxic substance methylmercury.

PMID- 21875054
TI  - Minimizing risks from spilled oil to ecosystem services using influence diagrams:
      the Deepwater Horizon spill response.
AB  - Decision science tools can be used in evaluating response options and making
      inferences on risks to ecosystem services (ES) from ecological disasters.
      Influence diagrams (IDs) are probabilistic networks that explicitly represent the
      decisions related to a problem and their influence on desired or undesired
      outcomes. To examine how IDs might be useful in probabilistic risk management for
      spill response efforts, an ID was constructed to display the potential
      interactions between exposure events and the trade-offs between costs and ES
      impacts from spilled oil and response decisions in the DWH spill event.
      Quantitative knowledge was not formally incorporated but an ID platform for doing
      this was examined. Probabilities were assigned for conditional relationships in
      the ID and scenarios examining the impact of different response actions on
      components of spilled oil were investigated in hypothetical scenarios. Given the
      structure of the ID, potential knowledge gaps included understanding of the
      movement of oil, the ecological risk of different spill-related stressors to key
      receptors (e.g., endangered species, fisheries), and the need for stakeholder
      valuation of the ES benefits that could be impacted by a spill. Framing the
      Deepwater Horizon problem domain in an ID conceptualized important variables and
      relationships that could be optimally accounted for in preparing and managing
      responses in future spills. These features of the developed IDs may assist in
      better investigating the uncertainty, costs, and the trade-offs if large-scale,
      deep ocean spills were to occur again.

PMID- 21875055
TI  - Direct quantification of inorganic polyphosphate in microbial cells using 4'-6
      diamidino-2-phenylindole (DAPI).
AB  - Inorganic polyphosphate (polyP) is increasingly being recognized as an important
      phosphorus sink within the environment, playing a central role in phosphorus
      exchange and phosphogenesis. Yet despite the significant advances made in polyP
      research there is a lack of rapid and efficient analytical approaches for the
      quantification of polyP accumulation in microbial cultures and environmental
      samples. A major drawback is the need to extract polyP from cells prior to
      analysis. Due to extraction inefficiencies this can lead to an underestimation of
      both intracellular polyP levels and its environmental pool size: we observed 23
      58% loss of polyP using standard solutions and current protocols. Here we report
      a direct fluorescence based DAPI assay system which removes the requirement for
      prior polyP extraction before quantification. This increased the efficiency of
      polyP detection by 28-55% in microbial cultures suggesting quantitative
      measurement of the intracellular polyP pool. It provides a direct polyP assay
      which combines quantification capability with technical simplicity. This is an
      important step forward in our ability to explore the role of polyP in cellular
      biology and biogeochemical nutrient cycling.

PMID- 21875056
TI  - Concise total synthesis and stereochemical revision of (+)-naseseazines A and B:
      regioselective arylative dimerization of diketopiperazine alkaloids.
AB  - Concise and enantioselective total syntheses of (+)-naseseazines A and B are
      described. Our regioselective and directed dimerization of diketopiperazines
      provides their critical C3-C(sp(2)) linkages, an assembly with plausible
      biogenetic relevance. We revise the absolute stereochemistry of (+)-naseseazines
      A and B.

PMID- 21875057
TI  - Metal ion mediated self-assembly directed formation of protein arrays.
AB  - Self-assembled inorganic-protein arrays with well-defined and controllable size
      and structure were obtained through the Fe(II) complexation of protein-conjugated
      terpyridine units (ligand). The atom-level control of the ligand is obtained
      through residue-specific conjugation between the complexing unit (terpy)
      containing an activity-based probe and a corresponding active enzyme (papain).
      The Fe(II)-based self-assembly performed on this unique building block (ligand)
      leads to chemical species of unprecedented constitution. The first example
      presented herein opens the way to a shape and size regime usually reserved to
      polymers.

PMID- 21875059
TI  - One-pot synthesis of novel photochromic oxazine compounds.
AB  - A one-pot domino synthesis of photochromic 2,2-diarylphenanthro-(9,10)-[2H]-[1,4]
      oxazines in excellent yield is described starting with acrylic acid derivatives.
      The reaction mechanism was studied by ReactIR and UV-vis. The cascade sequence of
      the reactions involves five transformations, namely, acyl azide formation,
      Curtius rearrangement, arsonium ylide formation, aza-Wittig, and final
      cyclization to the title compounds.

PMID- 21875060
TI  - Synthesis, characterization, and electronic structure of new type of
      heterometallic boride clusters.
AB  - The reaction of [Cp*TaCl(4)], 1 (Cp* = eta(5)-C(5)Me(5)), with [LiBH(4).THF] at 
      78  degrees C, followed by thermolysis in the presence of excess [BH(3).THF],
      results in the formation of the oxatantalaborane cluster [(Cp*Ta)(2)B(4)H(10)O],
      2 in moderate yield. Compound 2 is a notable example of an oxatantalaborane
      cluster where oxygen is contiguously bound to both the metal and boron. Upon
      availability of 2, a room temperature reaction was performed with [Fe(2)(CO)(9)],
      which led to the isolation of [(Cp*Ta)(2)B(2)H(4)O{H(2)Fe(2)(CO)(6)BH}], 3.
      Compound 3 is an unusual heterometallic boride cluster in which the [Ta(2)Fe(2)]
      atoms define a butterfly framework with one boron atom lying in a semi
      interstitial position. Likewise, the diselenamolybdaborane,
      [(Cp*Mo)(2)B(4)H(4)Se(2)], 4 was treated with an excess of [Fe(2)(CO)(9)] to
      afford the heterometallic boride cluster [(Cp*MoSe)(2)Fe(6)(CO)(13)B(2)(BH)(2)],
      5. The cluster core of 5 consists of a cubane [Mo(2)Se(2)Fe(2)B(2)] and a
      tricapped trigonal prism [Fe(6)B(3)] fused together with four atoms held in
      common between the two subclusters. In the tricapped trigonal prism subunit, one
      of the boron atoms is completely encapsulated and bonded to six iron and two
      boron atoms. Compounds 2, 3, and 5 have been characterized by mass spectrometry,
      IR, (1)H, (11)B, (13)C NMR spectroscopy, and the geometric structures were
      unequivocally established by crystallographic analysis. The density functional
      theory calculations yielded geometries that are in close agreement with the
      observed structures. Furthermore, the calculated (11)B NMR chemical shifts also
      support the structural characterization of the compounds. Natural bond order
      analysis and Wiberg bond indices are used to gain insight into the bonding
      patterns of the observed geometries of 2, 3, and 5.

PMID- 21875058
TI  - Rank order entropy: why one metric is not enough.
AB  - The use of Quantitative Structure-Activity Relationship models to address
      problems in drug discovery has a mixed history, generally resulting from the
      misapplication of QSAR models that were either poorly constructed or used outside
      of their domains of applicability. This situation has motivated the development
      of a variety of model performance metrics (r(2), PRESS r(2), F-tests, etc.)
      designed to increase user confidence in the validity of QSAR predictions. In a
      typical workflow scenario, QSAR models are created and validated on training sets
      of molecules using metrics such as Leave-One-Out or many-fold cross-validation
      methods that attempt to assess their internal consistency. However, few current
      validation methods are designed to directly address the stability of QSAR
      predictions in response to changes in the information content of the training
      set. Since the main purpose of QSAR is to quickly and accurately estimate a
      property of interest for an untested set of molecules, it makes sense to have a
      means at hand to correctly set user expectations of model performance. In fact,
      the numerical value of a molecular prediction is often less important to the end
      user than knowing the rank order of that set of molecules according to their
      predicted end point values. Consequently, a means for characterizing the
      stability of predicted rank order is an important component of predictive QSAR.
      Unfortunately, none of the many validation metrics currently available directly
      measure the stability of rank order prediction, making the development of an
      additional metric that can quantify model stability a high priority. To address
      this need, this work examines the stabilities of QSAR rank order models created
      from representative data sets, descriptor sets, and modeling methods that were
      then assessed using Kendall Tau as a rank order metric, upon which the Shannon
      entropy was evaluated as a means of quantifying rank-order stability. Random
      removal of data from the training set, also known as Data Truncation Analysis
      (DTA), was used as a means for systematically reducing the information content of
      each training set while examining both rank order performance and rank order
      stability in the face of training set data loss. The premise for DTA ROE model
      evaluation is that the response of a model to incremental loss of training
      information will be indicative of the quality and sufficiency of its training
      set, learning method, and descriptor types to cover a particular domain of
      applicability. This process is termed a "rank order entropy" evaluation or ROE.
      By analogy with information theory, an unstable rank order model displays a high
      level of implicit entropy, while a QSAR rank order model which remains nearly
      unchanged during training set reductions would show low entropy. In this work,
      the ROE metric was applied to 71 data sets of different sizes and was found to
      reveal more information about the behavior of the models than traditional metrics
      alone. Stable, or consistently performing models, did not necessarily predict
      rank order well. Models that performed well in rank order did not necessarily
      perform well in traditional metrics. In the end, it was shown that ROE metrics
      suggested that some QSAR models that are typically used should be discarded. ROE
      evaluation helps to discern which combinations of data set, descriptor set, and
      modeling methods lead to usable models in prioritization schemes and provides
      confidence in the use of a particular model within a specific domain of
      applicability.

PMID- 21875061
TI  - Probing the charge-transfer dynamics in DNA at the single-molecule level.
AB  - Photoinduced charge-transfer fluorescence quenching of a fluorescent dye produces
      the nonemissive charge-separated state, and subsequent charge recombination makes
      the reaction reversible. While the information available from the photoinduced
      charge-transfer process provides the basis for monitoring the microenvironment
      around the fluorescent dyes and such monitoring is particularly important in live
      cell imaging and DNA diagnosis, the information obtainable from the charge
      recombination process is usually overlooked. When looking at fluorescence emitted
      from each single fluorescent dye, photoinduced charge-transfer, charge-migration,
      and charge recombination cause a "blinking" of the fluorescence, in which the
      charge-recombination rate or the lifetime of the charge-separated state (tau) is
      supposed to be reflected in the duration of the off time during the single
      molecule-level fluorescence measurement. Herein, based on our recently developed
      method for the direct observation of charge migration in DNA, we utilized DNA as
      a platform for spectroscopic investigations of charge-recombination dynamics for
      several fluorescent dyes: TAMRA, ATTO 655, and Alexa 532, which are used in
      single-molecule fluorescence measurements. Charge recombination dynamics were
      observed by transient absorption measurements, demonstrating that these
      fluorescent dyes can be used to monitor the charge-separation and charge
      recombination events. Fluorescence correlation spectroscopy (FCS) of ATTO 655
      modified DNA allowed the successful measurement of the charge-recombination
      dynamics in DNA at the single-molecule level. Utilizing the injected charge just
      like a pulse of sound, such as a "ping" in active sonar systems, information
      about the DNA sequence surrounding the fluorescent dye was read out by measuring
      the time it takes for the charge to return.

PMID- 21875062
TI  - Online monitoring of water toxicity by use of bioluminescent reporter bacterial
      biochips.
AB  - We describe a flow-through biosensor for online continuous water toxicity
      monitoring. At the heart of the device are disposable modular biochips
      incorporating agar-immobilized bioluminescent recombinant reporter bacteria, the
      responses of which are probed by single-photon avalanche diode detectors. To
      demonstrate the biosensor capabilities, we equipped it with biochips harboring
      both inducible and constitutive reporter strains and exposed it to a continuous
      water flow for up to 10 days. During these periods we challenged the biosensor
      with 2-h pulses of water spiked with model compounds representing different
      classes of potential water pollutants, as well as with a sample of industrial
      wastewater. The biosensor reporter panel detected all simulated contamination
      events within 0.5-2.5 h, and its response was indicative of the nature of the
      contaminating chemicals. We believe that a biosensor of the proposed design can
      be integrated into future water safety and security networks, as part of an early
      warning system against accidental or intentional water pollution by toxic
      chemicals.

PMID- 21875063
TI  - Quinoline antimalarials containing a dibemethin group are active against
      chloroquinone-resistant Plasmodium falciparum and inhibit chloroquine transport
      via the P. falciparum chloroquine-resistance transporter (PfCRT).
AB  - A series of 4-amino-7-chloroquinolines with dibenzylmethylamine (dibemethin) side
      chains were shown to inhibit synthetic hemozoin formation. These compounds were
      equally active against cultures of chloroquine-sensitive (D10) and chloroquine
      resistant (K1) Plasmodium falciparum. The most active compound had an IC(50)
      value comparable to that of chloroquine, and its potency was undiminished when
      tested in three additional chloroquine-resistant strains. The three most active
      compounds exhibited little or no cytotoxicity in a mammalian cell line. When
      tested in vivo against mouse malaria via oral administration, two of the
      dibemethin derivatives reduced parasitemia by over 99%, with mice treated at 100
      mg/kg surviving the full length of the experiment. Three of the compounds were
      also shown to inhibit chloroquine transport via the parasite's chloroquine
      resistance transporter (PfCRT) in a Xenopus oocyte expression system. This
      constitutes the first example of a dual-function antimalarial for which the
      ability to inhibit both hemozoin formation and PfCRT has been demonstrated
      directly.

PMID- 21875064
TI  - Electrochemical sensing platform based on polyelectrolyte-surfactant
      supramolecular assemblies incorporating carbon nanotubes.
AB  - The characterization and application of a polyelectrolyte-surfactant
      supramolecular assembly formed by poly(allylamine) and dodecyl sulfate (PA-DS) on
      a screen-printed graphite electrode for the preparation of electrochemical
      sensing platforms are presented. The system was characterized by X-ray
      reflectometry (XRR) and grazing-incidence small-angle X-ray scattering (GISAXS)
      and tested with four benchmark electrochemical probes undergoing different
      electron-transfer mechanisms on carbon: ferrocyanide, hexaammineruthenium,
      ascorbic acid, and dopamine. The polyelectrolyte acts as a scaffold favoring the
      incorporation of the ferrocyanide, an ion oppositely charged to poly(allylamine).
      Also, its ability to incorporate carbon nanotubes (CNT) is presented. The
      composite material PA-DS-CNT is able to electrocatalyze the oxidation of
      dopamine, allowing its detection at micromolar levels in the presence of 100
      times higher concentrations of ascorbate and it is shown to be stable, while XRR
      and GISAXS results confirm a lamellar structure with well-defined domains, not
      perturbed by the presence of the CNT. The dispersion is easily prepared in
      aqueous solution and could facilitate the processing of the CNT with an efficient
      loading and yielding a more robust carbon-based material for sensing
      applications.

PMID- 21875065
TI  - Regio- and stereoselective syntheses of the natural product CCR5 antagonist
      anibamine and its three olefin isomers.
AB  - The syntheses of the natural product anibamine and its three olefin isomers have
      been achieved concisely and efficiently via highly regio- and stereoselective
      reactions. The crucial steps included a regioselective palladium-catalyzed
      alkynylation by Sonogashira coupling and a stereoselective Suzuki coupling.
      Further conformation analyses and in vitro calcium mobilization studies were
      carried out to characterize the compounds' biological properties.

PMID- 21875066
TI  - Reversible heme-dependent regulation of human cystathionine beta-synthase by a
      flavoprotein oxidoreductase.
AB  - Human CBS is a PLP-dependent enzyme that clears homocysteine, gates the flow of
      sulfur into glutathione, and contributes to the biogenesis of H(2)S. The presence
      of a heme cofactor in CBS is enigmatic, and its conversion from the ferric- to
      ferrous-CO state inhibits enzyme activity. The low heme redox potential (-350 mV)
      has raised questions about the feasibility of the ferrous-CO state forming under
      physiological conditions. Herein, we provide the first evidence of reversible
      inhibition of CBS by CO in the presence of a human flavoprotein and NADPH. These
      data provide a mechanism for cross talk between two gas-signaling systems, CO and
      H(2)S, via heme-mediated allosteric regulation of CBS.

PMID- 21875067
TI  - Laser spectroscopic and theoretical studies of encapsulation complexes of
      calix[4]arene.
AB  - The complexes between the host calix[4]arene (C4A) and various guest molecules
      such as NH(3), N(2), CH(4), and C(2)H(2) have been investigated via experimental
      and theoretical methods. The S(1)-S(0) electronic spectra of these guest-host
      complexes are observed by mass-selected resonant two-photon ionization (R2PI) and
      laser-induced fluorescence (LIF) spectroscopy. The IR spectra of the complexes
      formed in molecular beams are obtained by IR-UV double resonance (IR-UV DR) and
      IR photodissociation (IRPD) spectroscopy. The supramolecular structures of the
      complexes are investigated by electronic structure methods (density functional
      and second order perturbation theory). The current results for the various
      molecular guests are put in perspective with the previously reported ones for the
      C4A-rare gas (Rg) (Phys. Chem. Chem. Phys. 2007, 126, 141101) and C4A-H(2)O
      complexes (J. Phys. Chem. A, 2010, 114, 2967). The electronic spectra of the
      complexes of C4A with N(2), CH(4), and C(2)H(2) exhibit red-shifts of similar
      magnitudes with the ones observed for the C4A-Rg complexes, whereas the complexes
      of C4A with H(2)O and NH(3) show much larger red-shifts. Most of the IR-UV DR
      spectra of the complexes, except for C4A-C(2)H(2), show a broad hydrogen-bonded
      OH stretching band with a peak at ~3160 cm(-1). The analysis of the experimental
      results, in agreement with the ones resulting from the electronic structure
      calculations, suggest that C4A preferentially forms endo-complexes (guests inside
      the host calizarene cavity) with all the guest species reported in this study. We
      discuss the similarities and differences of the structures, binding energies, and
      the nature of the interaction between the C4A host and the various guest species.

PMID- 21875068
TI  - Reversible photoredox switching of porphyrin-bridged bis-2,6-di-tert
      butylphenols.
AB  - Porphyrin derivatives bearing 2,6-di-tert-butylphenol substituents at their 5,15
      positions undergo reversible photoredox switching between porphyrin and
      porphodimethene states as revealed by UV-vis spectroscopy, fluorescence
      spectroscopy, and X-ray single-crystal analyses. Photoredox interconversion is
      accompanied by substantial variations in electronic absorption and fluorescence
      emission spectra and a change of conformation of the tetrapyrrole macrocycle from
      planar to roof-shaped. Oxidation proceeds only under photoillumination of a
      dianionic state prepared through deprotonation using fluoride anions. Conversely,
      photoreduction occurs in the presence of a sacrificial electron donor. Transient
      absorption spectroscopy and electron spin resonance spectroscopy were applied to
      investigate the processes in photochemical reaction, and radical intermediates
      were characterized. That is, photooxidation initially results in a phenol
      substituent-centered radical, while the reduction process occurs via a
      delocalized radical state involving both the macrocycle and 5,15-substituents.
      Forward and reverse photochemical processes are governed by different chemical
      mechanisms, giving the important benefit that conversion reactions are completely
      isolated, leading to better separation of the end states. Furthermore, energy
      diagrams based on electrochemical analyses (cyclic voltammetry) were used to
      account for the processes occurring during the photochemical reactions. Our
      molecular design indicates a simple and versatile method for producing photoredox
      macrocyclic compounds, which should lead to a new class of advanced functional
      materials suitable for application in molecular devices and machines.

PMID- 21875069
TI  - Treatment of the multimode Jahn-Teller problem in small aromatic radicals.
AB  - The family of the Jahn-Teller (JT) active hydrocarbon rings, C(n)H(n) (n = 5-7),
      was analyzed by the means of multideterminantal density functional theory (DFT)
      approach. The multimode problem was addressed using the intrinsic distortion path
      (IDP) method, in which the JT distortion is expressed as a linear combination of
      all totally symmetric normal modes in the low symmetry minimum energy
      conformation. Partitioning of the stabilization energy into the various
      physically meaningful terms arising from Kohn-Sham DFT has been performed to get
      further chemical insight into the coupling of the nuclear movements and the
      electron distribution.

PMID- 21875070
TI  - In situ profiling of microbial communities in full-scale aerobic sequencing batch
      reactors treating winery waste in australia.
AB  - On-site aerobic sequencing batch reactor (SBR) treatment plants are implemented
      in many Australian wineries to treat the large volumes of associated wastewater
      they generate. Yet very little is known about their microbiology. This paper
      represents the first attempt to analyze the communities of three such systems
      sampled during both vintage and nonvintage operational periods using molecular
      methods. Alphaproteobacterial tetrad forming organisms (TFO) related to members
      of the genus Defluviicoccus and Amaricoccus dominated all three systems in both
      operational periods. Candidatus 'Alysiosphaera europaea' and Zoogloea were
      codominant in two communities. Production of high levels of exocellular capsular
      material by Zoogloea and Amaricoccus is thought to explain the poor settleability
      of solids in one of these plants. The dominance of these organisms is thought to
      result from the high COD to N/P ratios that characterize winery wastes, and it is
      suggested that manipulating this ratio with nutrient dosing may help control the
      problems they cause.

PMID- 21875071
TI  - Proteomic and transcriptomic analysis of linezolid resistance in Streptococcus
      pneumoniae.
AB  - Linezolid is an oxazolidinone antibiotic that inhibits the initiation of
      translation. Although resistance to linezolid is an uncommon event, it has been
      reported in clinical isolates. The genome sequence of Streptococcus pneumoniae
      linezolid-resistant mutants recently revealed mutations associated with
      resistance. A proteomic and transcriptomic screen now reveals a possible increase
      in the metabolism and transport of carbohydrates in these linezolid-resistant S.
      pneumoniae mutants. Several glycolytic proteins were shown to be overexpressed in
      the resistant strains, along with other enzymes and transporters involved in the
      metabolism of sugars. An increase in energy needs appears to be required to
      sustain extended levels of resistance to linezolid as the disruption of two ABC
      transporters putatively involved in the import of carbohydrates leads to a 2-fold
      sensitization to linezolid. Furthermore, the disruption of the catabolite control
      protein A, a regulator of the metabolism of sugars whose expression is highly
      increased in one linezolid-resistant mutant, resulted in a 2-fold increase in
      linezolid susceptibility. This global scale analysis of gene and protein
      expression profiling highlights metabolism alterations associated with linezolid
      resistance in S. pneumoniae.

PMID- 21875072
TI  - Synthesis of carboxymethylated and quaternized chitosans and their therapeutic
      effect on nonalcoholic Fatty liver disease.
AB  - O-Carboxymethyl chitosan (O-CMCs) and N-((2-hydroxy-3-N,N
      dimethylhexadecylammonium)propyl)chitosan chloride (N-CQCs) were synthesized for
      nonalcoholic fatty liver disease (NAFLD) treatment. The weight-average weight and
      substitution degree of O-CMCs and N-CQCs were 6.5 * 10(4) and 0.72 and 7.9 *
      10(4) and 0.21, respectively. O-CMCs was negatively charged with a zeta-potential
      value of -31.82 mV, whereas that of N-CQCs was +36.1 mV, and both showed low
      cytotoxcity. Serum lipid level and liver fat accumulation were reduced with
      chitosan and its two derivatives. Furthermore, mRNA and protein expression assay
      of hepatic lipid metabolism enzymes and low-density lipoprotein receptor (LDL-R)
      were observed by RT-PCR and Western blot. Results showed that N-CQCs exhibited a
      more evident desired effect than chitosan and O-CMCs, indicating that
      amphiphilicity, solubility, and surface charge of chitosan and its two
      derivatives played roles in the expression of hepatic lipid metabolism enzymes
      and LDL-R. Therefore, dietary supplementation of O-CMCs and N-CQCs can alleviate
      the high fat diet induced aberrations related to NAFLD by their antilipidemic
      property.

PMID- 21875073
TI  - Lessons from isolable nickel(I) precursor complexes for small molecule
      activation.
AB  - Small-molecule activation by transition metals is essential to numerous organic
      transformations, both biological and industrial. Creating useful metal-mediated
      activation systems often depends on stabilizing the metal with uncommon low
      oxidation states and low coordination numbers. This provides a redox-active metal
      center with vacant coordination sites well suited for interacting with small
      molecules. Monovalent nickel species, with their d(9) electronic configuration,
      are moderately strong one-electron reducing agents that are synthetically
      attractive if they can be isolated. They represent suitable reagents for closing
      the knowledge gap in nickel-mediated activation of small molecules. Recently, the
      first strikingly stable dinuclear beta-diketiminate nickel(I) precursor complexes
      were synthesized, proving to be suitable promoters for small-molecule binding and
      activation. They have led to many unprecedented nickel complexes bearing
      activated small molecules in different reduction stages. In this Account, we
      describe selected achievements in the activation of nitrous oxide (N(2)O), O(2),
      the heavier chalcogens (S, Se, and Te), and white phosphorus (P(4)) through this
      beta-diketiminatonickel(I) precursor species. We emphasize the reductive
      activation of O(2), owing to its promise in oxidation processes. The one-electron
      reduced O(2) activation product, that is, the corresponding beta-diketiminato
      supported Ni-O(2) complex, is a genuine superoxonickel(II) complex, representing
      an important intermediate in the early stages of O(2) activation. It selectively
      acts as an oxygen-atom transfer agent, hydrogen-atom scavenger, or both towards
      exogenous organic substrates to yield oxidation products. The one-electron
      reduction of the superoxonickel(II) moiety was examined by using elemental
      potassium, beta-diketiminatozinc(II) chloride, and beta-diketiminatoiron(I)
      complexes, affording the first heterobimetallic complexes featuring a [NiO(2)M]
      subunit (M is K, Zn, or Fe). Through density functional theory (DFT)
      calculations, the geometric and electronic structures of these complexes were
      established and their distinctive reactivity, including the unprecedented
      monooxygenase-like activity of a bis(MU-oxo)nickel-iron complex, was studied. The
      studies have further led to other heterobimetallic complexes containing a
      [NiO(2)M] core, which are useful for understanding the influence of the
      heterometal on structure-reactivity relationships. The activation of N(2)O led
      directly to the hydrogen-atom abstraction product bis(MU-hydroxo)nickel(II)
      species and prevented isolation of any intermediate. In contrast, the activation
      of elemental S, Se, and Te with the same nickel(I) reagent furnished activation
      products with superchalcogenido E(2)(-) (E is S, Se, or Te) and dichalcogenido
      E(2)(2-) ligand in different activation stages. The isolable
      supersulfidonickel(II) subunit may serve as a versatile building block for the
      synthesis of heterobimetallic disulfidonickel(II) complexes with a [NiS(2)M]
      core. In the case of white phosphorus, the P(4) molecule has been coordinated to
      the nickel(I) center of dinuclear beta-diketiminatonickel(I) precursor complexes;
      however, the whole P(4) subunit is a weaker electron acceptor than the
      dichalcogen ligands E(2), thus remaining unreduced. This P(4) binding mode is
      rare and could open new doors for subsequent functionalization of P(4). Our
      advances in understanding how these small molecules are bound to a nickel(I)
      center and are activated for further transformation offer promise for designing
      new catalysts. These nickel-containing complexes offer exceptional potential for
      nickel-mediated transformations of organic molecules and as model compounds for
      mimicking active sites of nickel-containing metalloenzymes.

PMID- 21875075
TI  - Modulating optical properties of graphene oxide: role of prominent functional
      groups.
AB  - To modulate the electronic and optical properties of graphene oxide via
      controlled deoxidation, a proper understanding of the role of the individual
      functional group in determining these properties is required. We, therefore, have
      performed ab initio density functional theory based calculations to study the
      electronic and optical properties of model structures of graphene oxide with
      different coverages and compositions. In particular, we considered various
      concentrations of major functional groups like epoxides, hydroxyls, and
      carbonyls, which mainly consititute the graphene oxide and the reduced graphene
      oxide. Our calculated electron energy loss spectra (EELS) demonstrate the pi
      plasmon peak to be less sensitive, while pi + sigma plasmon is found to have a
      significant blue shift of about 1.0-3.0 eV, when the concentration of epoxy and
      hydroxyl functional groups in graphene oxide vary from 25% to 75%. However, the
      increase in carbonyl groups in the center of the graphene sheet creates holes,
      which lead to the red shift of the EELS. In the case of 37.5% of oxygen-to-carbon
      ratio, we find the pi plasmon peak to be shifted by roughly 1.0 eV as compared to
      that of the pristine graphene. Our results agree well with the experimental
      findings which suggest a blue shift in the EELS of graphene oxide and an
      absorption feature due to a pi electron transition of the carbonyl groups at a
      lower energy than that of epoxy and hydroxyl groups. We also show that the
      increase in the width of the hole created by the carbonyl groups significantly
      decreases the optical gap and opens the band gap, and thus, we argue that reduced
      graphene oxide with mostly carbonyl groups could be a useful material for
      developing tunable opto-electronic nanodevices.

PMID- 21875074
TI  - Production of ES1 plasma carboxylesterase knockout mice for toxicity studies.
AB  - The LD(50) for soman is 10-20-fold higher for a mouse than a human. The
      difference in susceptibility is attributed to the presence of carboxylesterase in
      mouse but not in human plasma. Our goal was to make a mouse lacking plasma
      carboxylesterase. We used homologous recombination to inactivate the
      carboxylesterase ES1 gene on mouse chromosome 8 by deleting exon 5 and by
      introducing a frame shift for amino acids translated from exons 6 to 13. ES1-/-
      mice have no detectable carboxylesterase activity in plasma but have normal
      carboxylesterase activity in tissues. Homozygous ES1-/- mice and wild-type
      littermates were tested for response to a nerve agent model compound (soman
      coumarin) at 3 mg/kg sc. This dose intoxicated both genotypes but was lethal only
      to ES1-/- mice. This demonstrated that plasma carboxylesterase protects against a
      relatively high toxicity organophosphorus compound. The ES1-/- mouse should be an
      appropriate model for testing highly toxic nerve agents and for evaluating
      protection strategies against the toxicity of nerve agents.

PMID- 21875076
TI  - Density functional study of the stable oxidation states and the binding of oxygen
      in MO4 clusters of the 3d elements.
AB  - The tetraoxide clusters with stoichiometry MO(4), and the structural isomers with
      side-on and end-on bonded dioxygen, are studied by DFT with the B1LYP functional.
      Diperoxides M(O(2))(2) are the most stable clusters at the beginning (Sc, Ti) and
      at the end of the row (Co-Cu), the latter being planar. For V, Cr, and Mn, the
      dioxoperoxides O(2)M(O(2)) are the most stable isomers. Low-spin states are
      dominant for the nonplanar diperoxides M(O(2))(2) and dioxoperoxides O(2)M(O(2)),
      and the local magnetic moment at the metal cations is small. The local charge on
      the metal cation center is higher in the diperoxides of Sc and Ti; it drops
      significantly in the dioxoperoxides of V and Cr. The iron dioxosuperoxide in the
      (3)A'' state, which contains end-on bonded dioxygen, OOFeO(2), is an exception
      with higher charge on Fe. In the planar diperoxides of Co, Ni, and Cu, oxygen-to
      metal charge transfer is significant, and the local charge on the metal cation is
      close to 1. In all tetraoxygen clusters of the 3d elements, the cation center
      remains strongly electrophilic and interacts with Ar atoms from the inert-gas
      matrix, where the clusters are trapped for IR spectral studies. Significant
      frequency shifts in the matrix are found for the dioxoperoxide of vanadium,
      O(2)V(O(2)), the dioxosuperoxide of iron, OOFeO(2), and the nickel diperoxide,
      Ni(O(2))(2).

PMID- 21875079
TI  - Zinc blende and wurtzite crystal phase mixing and transition in indium phosphide
      nanowires.
AB  - Indium phosphide (InP) nanowires, which have crystal phase mixing and transition
      from zinc blende (ZB) to wurtzite (WZ), are grown in intermediate growth
      conditions between ZB and WZ by using selective-area metalorganic vapor phase
      epitaxy (SA-MOVPE). The shape of InP nanowires is tapered unlike ZB or WZ
      nanowires. A growth model has been developed for the tapered nanowires, which is
      simply described as the relationship between tapered angle and the ratio of ZB
      and WZ segments. In addition, the peak energy shift in photoluminescence
      measurement was attributed to the quantum confinement effect of the quantum well
      of the ZB region located in the polytypic structure of ZB and WZ in nanowires.

PMID- 21875080
TI  - Ecologically informed engineering reduces loss of intertidal biodiversity on
      artificial shorelines.
AB  - Worldwide responses to urbanization, expanding populations and climatic change
      mean biodiverse habitats are replaced with expensive, but necessary
      infrastructure. Coastal cities support vast expanses of buildings and roads along
      the coast or on "reclaimed" land, leading to "armouring" of shorelines with
      walls, revetments and offshore structures to reduce erosion and flooding.
      Currently infrastructure is designed to meet engineering and financial criteria,
      without considering its value as habitat, despite artificial shorelines causing
      loss of intertidal species and altering ecological natural processes that sustain
      natural biodiversity. Most research on ameliorating these impacts focus on soft
      sediment habitats and larger flora (e.g., restoring marshes, encouraging plants
      to grow on walls). In response to needs for greater collaboration between
      ecologists and engineers to create infrastructure to better support biodiversity,
      we show how such collaborations lead to small-scale and inexpensive ecologically
      informed engineering which reduces loss of species of algae and animals from
      rocky shores replaced by walls. Adding experimental novel habitats to walls
      mimicking rock-pools (e.g., cavities, attaching flowerpots) increased numbers of
      species by 110% within months, in particular mobile animals most affected by
      replacing natural shores with walls. These advances provide new insights about
      melding engineering and ecological knowledge to sustain biodiversity in cities.

PMID- 21875077
TI  - Characterization of multiprotein complexes of the Borrelia burgdorferi outer
      membrane vesicles.
AB  - Among bacterial cell envelopes, the Borrelia burgdorferi outer membrane (OM) is
      structurally unique in that the identities of many protein complexes remain
      unknown; however, their characterization is the first step toward our
      understanding of membrane protein interactions and potential functions. Here, we
      used two-dimensional blue native/SDS-PAGE/mass spectrometric analysis for a
      global characterization of protein-protein interactions as well as to identify
      protein complexes in OM vesicles isolated from multiple infectious sensu stricto
      isolates of B. burgdorferi. Although we uncovered the existence of at least 10
      distinct OM complexes harboring several unique subunits, the complexome is
      dominated by the frequent occurrence of a limited diversity of membrane proteins,
      most notably P13, outer surface protein (Osp) A, -B, -C, and -D and Lp6.6. The
      occurrence of these complexes and specificity of subunit interaction were further
      supported by independent two-dimensional immunoblotting and coimmunoprecipitation
      assays as well as by mutagenesis studies, where targeted depletion of a subunit
      member (P66) selectively abolished a specific complex. Although a comparable
      profile of the OM complexome was detected in two major infectious isolates, such
      as B31 and 297, certain complexes are likely to occur in an isolate-specific
      manner. Further assessment of protein complexes in multiple Osp-deficient
      isolates showed loss of several protein complexes but revealed the existence of
      additional complex/subunits that are undetectable in wild-type cells. Together,
      these observations uncovered borrelial antigens involved in membrane protein
      interactions. The study also suggests that the assembly process of OM complexes
      is specific and that the core or stabilizing subunits vary between complexes.
      Further characterization of these protein complexes including elucidation of
      their biological significance may shed new light on the mechanism of pathogen
      persistence and the development of preventative measures against the infection.

PMID- 21875078
TI  - Targeting multiple conformations leads to small molecule inhibitors of the
      uPAR.uPA protein-protein interaction that block cancer cell invasion.
AB  - Interaction of the urokinase receptor (uPAR) with its binding partners such as
      the urokinase-type plasminogen activator (uPA) at the cell surface triggers a
      series of proteolytic and signaling events that promote invasion and metastasis.
      Here, we report the discovery of a small molecule (IPR-456) and its derivatives
      that inhibit the tight uPAR.uPA protein-protein interaction. IPR-456 was
      discovered by virtual screening against multiple conformations of uPAR sampled
      from explicit-solvent molecular dynamics simulations. Biochemical
      characterization reveal that the compound binds to uPAR with submicromolar
      affinity (K(d) = 310 nM) and inhibits the tight protein-protein interaction with
      an IC(50) of 10 MUM. Free energy calculations based on explicit-solvent molecular
      dynamics simulations suggested the importance of a carboxylate moiety on IPR-456,
      which was confirmed by the activity of several derivatives including IPR-803.
      Immunofluorescence imaging showed that IPR-456 inhibited uPA binding to uPAR of
      breast MDA-MB-231 tumor cells with an IC(50) of 8 MUM. The compounds blocked MDA
      MB-231 cell invasion, but IPR-456 showed little effect on MDA-MB-231 migration
      and no effect on adhesion, suggesting that uPAR mediates these processes through
      its other binding partners.

PMID- 21875081
TI  - Sequence-specific single-molecule analysis of 8-oxo-7,8-dihydroguanine lesions in
      DNA based on unzipping kinetics of complementary probes in ion channel
      recordings.
AB  - Translocation measurements of intact DNA strands with the ion channel alpha
      hemolysin (alpha-HL) are limited to single-stranded DNA (ssDNA) experiments as
      the dimensions of the channel prevent double-stranded DNA (dsDNA) translocation;
      however, if a short oligodeoxynucleotide is used to interrogate a longer ssDNA
      strand, it is possible to unzip the duplex region when it is captured in the
      alpha-HL vestibule, allowing the longer strand to translocate through the alpha
      HL channel. This unzipping process has a characteristic duration based on the
      stability of the duplex. Here, ion channel recordings are used to detect the
      presence and relative location of the oxidized damage site 8-oxo-7,8
      dihydroguanine (OG) in a sequence-specific manner. OG engages in base pairing to
      C or A with unique stabilities relative to native base Watson-Crick pairings, and
      this phenomenon is used here to engineer probe sequences (10-15mers) that, when
      base-paired with a 65mer sequence of interest, containing either G or OG at a
      single site, produce characteristic unzipping times that correspond well with the
      duplex melting temperature (T(m)). Unzipping times also depend on the direction
      from which the duplex enters the vestibule if the stabilities of leading base
      pairs at the ends of the duplex are significantly different. It is shown here
      that the presence of a single DNA lesion can be distinguished from an undamaged
      sequence and that the relative location of the damage site can be determined
      based on the duration of duplex unzipping.

PMID- 21875082
TI  - ONIOM(DFT:MM) study of 2-hydroxyethylphosphonate dioxygenase: what determines the
      destinies of different substrates?
AB  - Why can enzymes provide different products from only slightly different
      substrates? While the reaction of 2-hydroxyethylphosphonate (2-HEP) catalyzed by
      2-hydroxyethylphosphonate dioxygenase (HEPD) yields hydroxymethylphosphonate and
      formic acid, the HEPD-catalyzed reaction of 1-HEP gives acetylphosphate.
      ONIOM(DFT:MM) was used to uncover the distinct reaction mechanisms for the
      different substrates. Calculations show that, in both reactions, similar radical
      intermediates are generated by the same process. After the formation of common
      radical intermediates, proton-coupled electron transfer (PCET) operates in the 1
      HEP reaction, whereas in the 2-HEP reaction, it cannot occur and an alternative
      pathway sets in. Thus, the PCET plays a critical role in defining the fates of
      the substrates.

PMID- 21875083
TI  - Aryl functionalization as a route to band gap engineering in single layer
      graphene devices.
AB  - Chemical functionalization is a promising route to band gap engineering of
      graphene. We chemically grafted nitrophenyl groups onto exfoliated single-layer
      graphene sheets in the form of substrate-supported or free-standing films. Our
      transport measurements demonstrate that nonsuspended functionalized graphene
      behaves as a granular metal, with variable range hopping transport and a mobility
      gap ~0.1 eV at low temperature. For suspended graphene that allows
      functionalization on both surfaces, we demonstrate tuning of its electronic
      properties from a granular metal to a semiconductor in which transport occurs via
      thermal activation over a transport gap ~80 meV from 4 to 300 K. This noninvasive
      and scalable functionalization technique paves the way for CMOS-compatible band
      gap engineering of graphene electronic devices.

PMID- 21875084
TI  - Diversity-oriented synthesis of 13- to 18-membered macrolactams via ring-closing
      metathesis.
AB  - An efficient build/couple/pair approach to diversity-oriented synthesis was
      employed to access several structurally complex macrolactams. In this paper, we
      describe the successful evaluation of ring-closing metathesis toward the
      systematic generation of skeletal diversity. By appropriately varying the nature
      and chain length of the alkenol fragment, a diverse collection of 13- to 18
      membered macrolactams were obtained.

PMID- 21875086
TI  - Transformative two-dimensional layered nanocrystals.
AB  - Regioselective chemical reactions and structural transformations of two
      dimensional (2D) layered transition-metal chalcogenide (TMC) nanocrystals are
      described. Upon exposure of 2D TiS(2) nanodiscs to a chemical stimulus, such as
      Cu ion, selective chemical reaction begins to occur at the peripheral edges. This
      edge reaction is followed by ion diffusion, which is facilitated by interlayer
      nanochannels and leads to the formation of a heteroepitaxial TiS(2)-Cu(2)S
      intermediate. These processes eventually result in the generation of a single
      crystalline, double-convex toroidal Cu(2)S nanostructure. Such 2D regioselective
      chemical reactions also take place when other ionic reactants are used. The
      observations made and chemical principles uncovered in this effort indicate that
      a general approach exists for building various toroidal nanocrystals of
      substances such as Ag(2)S, MnS, and CdS.

PMID- 21875085
TI  - Interaction between the D2 dopamine receptor and neuronal calcium sensor-1
      analyzed by fluorescence anisotropy.
AB  - Neuronal calcium sensor-1 (NCS-1) is a small calcium binding protein that plays a
      key role in the internalization and desensitization of activated D2 dopamine
      receptors (D2Rs). Here, we have used fluorescence anisotropy (FA) and a panel of
      NCS-1 EF-hand variants to interrogate the interaction between the D2R and NCS-1.
      Our data are consistent with the following conclusions. (1) FA titration
      experiments indicate that at low D2R peptide concentrations calcium-loaded NCS-1
      binds to the D2R peptide in a monomeric form. At high D2R peptide concentrations,
      the FA titration data are best fit by a model in which the D2R peptide binds two
      NCS-1 monomers sequentially in a cooperative fashion. (2) Competition FA
      experiments in which unlabeled D2R peptide was used to compete with labeled
      peptide for binding to NCS-1 shifted titration curves to higher NCS-1
      concentrations, suggesting that the binding of NCS-1 to the D2R is highly
      specific and that binding occurs in a cooperative fashion. (3) N-Terminally
      myristoylated NCS-1 dimerizes in a calcium-dependent manner. (4) Co
      immunoprecipitation experiments in HEK-293 confirm that NCS-1 can oligomerize in
      cell lysates and that oligomerization is dependent on calcium binding and
      requires functionally intact EF-hand domains. (5) Ca(2+)/Mg(2+) FA titration
      experiments revealed that NCS-1 EF-hands 2-4 (EF2-4) contributed to binding with
      the D2R peptide. EF2 appears to have the highest affinity for Ca(2+), and
      occupancy of this site is sufficient to promote high-affinity binding of the NCS
      1 monomer to the D2R peptide. Magnesium ions may serve as a physiological
      cofactor with calcium for NCS-1-D2R binding. Finally, we propose a structural
      model that predicts that the D2R peptide binds to the first 60 residues of NCS-1.
      Together, our results support the possibility of using FA to screen for small
      molecule drugs that can specifically block the interaction between the D2R and
      NCS-1.

PMID- 21875088
TI  - Activation of CO2 by a heterobimetallic Zr/Co complex.
AB  - At room temperature, the early/late heterobimetallic complex
      Co((i)Pr(2)PNMes)(3)Zr(THF) has been shown to oxidatively add CO(2), generating
      (OC)Co((i)Pr(2)PNMes)(2)(MU-O)Zr((i)Pr(2)PNMes). This compound can be further
      reduced under varying conditions to generate either the Zr oxoanion (THF)(3)Na-O
      Zr(MesNP(i)Pr(2))(3)Co(CO) or the Zr carbonate complex (THF)(4)Na(2)(CO(3))
      Zr(MesNP(i)Pr(2))(3)Co(CO). Additionally, reactivity of the CO(2)-derived product
      has been observed with PhSiH(3) to generate the Co-hydride/Zr-siloxide product
      (OC)(H)Co((i)Pr(2)PNMes)(3)ZrOSiH(2)Ph.

PMID- 21875089
TI  - Effect of solvent annealing on the tensile deformation mechanism of a colloidal
      crystalline polymeric latex film.
AB  - The influence of solvent annealing on microscopic deformational behavior of a
      styrene/n-butyl acrylate copolymer latex film subjected to uniaxial tensile
      deformation was studied by small-angle X-ray scattering. It was demonstrated that
      the microscopic deformation mechanism of the latex films transformed from a
      nonaffine deformation behavior to an affine deformation behavior after solvent
      annealing. This was attributed to the interdiffusion of polymeric chains between
      adjacent swollen latex particles in the film. It turns out that solvent annealing
      is much more efficient than thermal annealing due to a much slow evaporation
      process after solvent annealing.

PMID- 21875090
TI  - Nanopatterning of functional materials by gas phase pattern deposition of self
      assembled molecular thin films in combination with electrodeposition.
AB  - We present a general methodology to pattern functional materials on the nanometer
      scale using self-assembled molecular templates on conducting substrates. A soft
      lithographic gas phase edge patterning process using poly(dimethylsiloxane) molds
      was employed to form electrically isolating organosilane patterns of a few
      nanometer thickness and a line width that could be tuned by varying the time of
      deposition. Electrodeposition was employed to deposit patterns of Ni and ZnO on
      these prepatterned substrates. Deposition occurred only on patches of the
      substrate where no organosilane monolayer was present. The process is simple,
      inexpensive, and scalable to large areas. We achieved formation of metallic and
      oxide material patterns with a lateral resolution of 80 nm.

PMID- 21875092
TI  - Synthesis of graphene nanoribbons encapsulated in single-walled carbon nanotubes.
AB  - A novel material, graphene nanoribbons encapsulated in single-walled carbon
      nanotubes (GNR@SWNT), was synthesized using confined polymerization and fusion of
      polycyclic aromatic hydrocarbon (PAH) molecules. Formation of the GNR is possible
      due to confinement effects provided by the one-dimensional space inside
      nanotubes, which helps to align coronene or perylene molecules edge to edge to
      achieve dimerization and oligomerization of the molecules into long nanoribbons.
      Almost 100% filling of SWNT with GNR is achieved while nanoribbon length is
      limited only by the length of the encapsulating nanotube. The PAH fusion reaction
      provides a very simple and easily scalable method to synthesize GNR@SWNT in
      macroscopic amounts. First-principle simulations indicate that encapsulation of
      the GNRs is energetically favorable and that the electronic structure of the
      encapsulated GNRs is the same as for the free-standing ones, pointing to possible
      applications of the GNR@SWNT structures in photonics and nanoelectronics.

PMID- 21875091
TI  - Meta-omic characterization of the marine invertebrate microbial consortium that
      produces the chemotherapeutic natural product ET-743.
AB  - In many macroorganisms, the ultimate source of potent biologically active natural
      products has remained elusive due to an inability to identify and culture the
      producing symbiotic microorganisms. As a model system for developing a meta-omic
      approach to identify and characterize natural product pathways from invertebrate
      derived microbial consortia, we chose to investigate the ET-743 (Yondelis)
      biosynthetic pathway. This molecule is an approved anticancer agent obtained in
      low abundance (10(-4)-10(-5) % w/w) from the tunicate Ecteinascidia turbinata and
      is generated in suitable quantities for clinical use by a lengthy semisynthetic
      process. On the basis of structural similarities to three bacterial secondary
      metabolites, we hypothesized that ET-743 is the product of a marine bacterial
      symbiont. Using metagenomic sequencing of total DNA from the tunicate/microbial
      consortium, we targeted and assembled a 35 kb contig containing 25 genes that
      comprise the core of the NRPS biosynthetic pathway for this valuable anticancer
      agent. Rigorous sequence analysis based on codon usage of two large unlinked
      contigs suggests that Candidatus Endoecteinascidia frumentensis produces the ET
      743 metabolite. Subsequent metaproteomic analysis confirmed expression of three
      key biosynthetic proteins. Moreover, the predicted activity of an enzyme for
      assembly of the tetrahydroisoquinoline core of ET-743 was verified in vitro. This
      work provides a foundation for direct production of the drug and new analogues
      through metabolic engineering. We expect that the interdisciplinary approach
      described is applicable to diverse host-symbiont systems that generate valuable
      natural products for drug discovery and development.

PMID- 21875094
TI  - Measurement of absolute absorption cross sections for nitrous acid (HONO) in the
      near-infrared region by the continuous wave cavity ring-down spectroscopy (cw
      CRDS) technique coupled to laser photolysis.
AB  - Absolute absorption cross sections for selected lines of the OH stretch overtone
      2nu(1) of the cis-isomer of nitrous acid HONO have been measured in the range
      6623.6-6645.6 cm(-1) using the continuous wave cavity ring-down spectroscopy (cw
      CRDS) technique. HONO has been generated by two different, complementary methods:
      in the first method, HONO has been produced by pulsed photolysis of H(2)O(2)/NO
      mixture at 248 nm, and in the second method HONO has been produced in a
      continuous manner by flowing humidified N(2) over 5.2 M HCl and 0.5 M NaNO(2)
      solutions. Laser photolysis synchronized with the cw-CRDS technique has been used
      to measure the absorption spectrum of HONO produced in the first method, and a
      simple cw-CRDS technique has been used in the second method. The first method,
      very time-consuming, allows for an absolute calibration of the absorption
      spectrum by comparison with the well-known HO(2) absorption cross section, while
      the second method is much faster and leads to a better signal-to-noise ratio. The
      strongest line in this wavelength range has been found at 6642.51 cm(-1) with
      sigma = (5.8 +/- 2.2) * 10(-21) cm(2).

PMID- 21875093
TI  - Design and synthesis of a novel triptycene-based ligand for modeling carboxylate
      bridged diiron enzyme active sites.
AB  - A novel triptycene-based ligand with a preorganized framework was designed to
      model carboxylate-bridged diiron active sites in bacterial multicomponent
      monooxygenase (BMM) hydroxylase enzymes. The synthesis of the bis(benzoxazole)
      appended ligand L1 depicted was accomplished in 11 steps. Reaction of L1 with
      iron(II) triflate and a carboxylate source afforded the desired diiron(II)
      complex [Fe(2)L1(MU-OH)(MU-O(2)CAr(Tol))(OTf)(2)].

PMID- 21875095
TI  - Nickel-catalyzed chelation-assisted transformations involving ortho C-H bond
      activation: regioselective oxidative cycloaddition of aromatic amides to alkynes.
AB  - Although the pioneering example of ortho metalation involving cleavage of C-H
      bonds was achieved using a nickel complex (Kleiman, J. P.; Dubeck, M. J. Am.
      Chem. Soc. 1963, 85, 1544), no examples of catalysis using nickel complexes have
      been reported. In this work, the Ni-catalyzed transformation of ortho C-H bonds
      utilizing chelation assistance, such as oxidative cycloaddition of aromatic
      amides with alkynes, has been achieved.

PMID- 21875096
TI  - Surface-confined nickel mediated cross-coupling reactions: characterization of
      initiator environment in Kumada catalyst-transfer polycondensation.
AB  - Kumada catalyst-transfer polycondensation (KCTP) has proven to be an excellent
      strategy toward the synthesis of well-defined conjugated polymers. In this
      report, Ni(0) species are reacted with surface-bound aryl bromides to yield KCTP
      initiators of structure (aryl)Ni(II)-Br. Surface-confined Kumada reactions are
      carried out with a ferrocene functionalized Grignard reagent to quantify
      initiator coverage, ligand exchange, and Kumada reaction kinetics. In addition,
      surface-initiated Kumada catalyst-transfer polycondensation (SI-KCTP) is carried
      out from the fabricated initiators to modify SiO(2) and ITO surfaces. Uniform
      poly(3-methylthiophene) films with thicknesses between 40 and 65 nm were
      characterized using a variety of spectroscopic and electrochemical techniques.

PMID- 21875097
TI  - Multichannel molecular switch with a surface-confined electroactive radical
      exhibiting tunable wetting properties.
AB  - A multichannel surface molecular switch based on self-assembled monolayers (SAMs)
      on gold of a novel polychlorotriphenylmethyl radical has been fabricated. These
      SAMs are electrically commutable between two stable redox states that reveal
      distinct magnetic, optical, and wetting properties that can be employed as read
      out mechanisms. The high stability and reversibility of systems like the one
      reported here further supports the vision of using molecules in the electronic
      devices of the future.

PMID- 21875098
TI  - Bioactive A-type proanthocyanidins from Cinnamomum cassia.
AB  - Two trimeric proanthocyanidins, cinnamtannin B-1 (1) and cinnamtannin D-1 (2),
      have been isolated from the bark of Cinnamomum cassia along with the known
      tetramer parameritannin A-1 (3) and a previously unreported tetramer, named
      cassiatannin A (4). The structures of 1-4 were elucidated on the basis of 1D and
      2D NMR, MS, and CD analyses and compared to the reported data. Proanthocyanidins
      (1-4) possess significant in vitro inhibitory activity against cyclooxygenase-2
      (COX-2) at micromolar concentrations.

PMID- 21875099
TI  - In situ transmission electron microscopy observation of pulverization of aluminum
      nanowires and evolution of the thin surface Al2O3 layers during lithiation
      delithiation cycles.
AB  - Lithiation-delithiation cycles of individual aluminum nanowires (NWs) with
      naturally oxidized Al(2)O(3) surface layers (thickness 4-5 nm) were conducted in
      situ in a transmission electron microscope. Surprisingly, the lithiation was
      always initiated from the surface Al(2)O(3) layer, forming a stable Li-Al-O glass
      tube with a thickness of about 6-10 nm wrapping around the NW core. After
      lithiation of the surface Al(2)O(3) layer, lithiation of the inner Al core took
      place, which converted the single crystal Al to a polycrystalline LiAl alloy,
      with a volume expansion of about 100%. The Li-Al-O glass tube survived the 100%
      volume expansion, by enlarging through elastic and plastic deformation, acting as
      a solid electrolyte with exceptional mechanical robustness and ion conduction.
      Voids were formed in the Al NWs during the initial delithiation step and grew
      continuously with each subsequent delithiation, leading to pulverization of the
      Al NWs to isolated nanoparticles confined inside the Li-Al-O tube. There was a
      corresponding loss of capacity with each delithiation step when arrays of NWs
      were galvonostatically cycled. The results provide important insight into the
      degradation mechanism of lithium-alloy electrodes and into recent reports about
      the performance improvement of lithium ion batteries by atomic layer deposition
      of Al(2)O(3) onto the active materials or electrodes.

PMID- 21875100
TI  - General and scalable amide bond formation with epimerization-prone substrates
      using T3P and pyridine.
AB  - The mild combination of T3P (n-propanephosphonic acid anhydride) and pyridine has
      been developed for low-epimerization amide bond formation and implemented for the
      synthesis of a key intermediate to a glucokinase activator. This robust method is
      general for the coupling of various racemization-prone acid substrates and
      amines, including relatively non-nucleophilic anilines, and provides amides in
      high yields with very low epimerization. With easy reaction setup and product
      isolation, this protocol offers several practical and experimental benefits.

PMID- 21875101
TI  - Trap-assisted tunneling in Si-InAs nanowire heterojunction tunnel diodes.
AB  - We report on the electrical characterization of one-sided p(+)-si/n-InAs nanowire
      heterojunction tunnel diodes to provide insight into the tunnel process occurring
      in this highly lattice mismatched material system. The lattice mismatch gives
      rise to dislocations at the interface as confirmed by electron microscopy.
      Despite this, a negative differential resistance with peak-to-valley current
      ratios of up to 2.4 at room temperature and with large current densities is
      observed, attesting to the very abrupt and high-quality interface. The presence
      of dislocations and other defects that increase the excess current is evident in
      the first and second derivative of the I-V characteristics as distinct peaks
      arising from trap-and phonon-assisted tunneling via the corresponding defect
      levels. We observe this assisted tunneling mainly in the forward direction and at
      low reverse bias but not at higher reverse biases because the band-to-band
      generation rates are peaked in the InAs, which is also confirmed by modeling.
      This indicates that most of the peaks are due to dislocations and defects in the
      immediate vicinity of the interface. Finally, we also demonstrate that these
      devices are very sensitive to electrical stress, in particular at room
      temperature, because of the extremely high electrical fields obtained at the
      abrupt junction even at low bias. The electrical stress induces additional defect
      levels in the band gap, which reduce the peak-to-valley current ratios.

PMID- 21875102
TI  - Arrays of ZnO/Zn(x)Cd(1-x)Se nanocables: band gap engineering and photovoltaic
      applications.
AB  - Arrays of ZnO/Zn(x)Cd(1-x)Se (0 <= x <= 1) core/shell nanocables with shells of
      tunable compositions have been synthesized on fluorine-doped tin oxide glass
      substrates via a simple ion-exchange approach. Through the effects of
      stoichiometry and type II heterojunction, optical absorptions of the nanocable
      arrays can be controllably tuned to cover almost the entire visible spectrum.
      Lattice parameters and band gaps of the ternary Zn(x)Cd(1-x)Se shells were found
      to have respectively linear and quadratic relationships with the Zn content (x).
      These ZnO/Zn(x)Cd(1-x)Se nanocable arrays are further demonstrated to be
      promising photoelectrodes for photoelectrochemical solar cells, giving a maximum
      power conversion efficiency up to 4.74%.

PMID- 21875103
TI  - Optimized spatial correlations for broadband light trapping nanopatterns in high
      efficiency ultrathin film a-Si:H solar cells.
AB  - Nanophotonic structures have attracted attention for light trapping in solar
      cells with the potential to manage and direct light absorption on the nanoscale.
      While both randomly textured and nanophotonic structures have been investigated,
      the relationship between photocurrent and the spatial correlations of random or
      designed surfaces has been unclear. Here we systematically design pseudorandom
      arrays of nanostructures based on their power spectral density, and correlate the
      spatial frequencies with measured and simulated photocurrent. The integrated cell
      design consists of a patterned plasmonic back reflector and a nanostructured
      semiconductor top interface, which gives broadband and isotropic photocurrent
      enhancement.

PMID- 21875104
TI  - Molecular simulation of gas adsorption, diffusion, and permeation in hydrated
      Nafion membranes.
AB  - Molecular simulations were performed to characterize hydrated Nafion membranes in
      terms of gas adsorption, diffusion, and permeation. The experimental results
      validate the molecular model of Nafion with respect to material density,
      morphology, free volume, and water diffusivity. Nafion's adsorption property is
      examined in terms of the solubility and adsorption isotherms for gases, including
      H(2), O(2), and N(2). The adsorption capacity of hydrated Nafion is shown to be
      strong for O(2) and N(2) but not for H(2). Due to the dilution effect, N(2) is
      able to suppress the loading of O(2) and protect the fuel cell from fuel
      crossover. The dynamic behaviors of H(2) and O(2) are represented by self
      diffusion coefficients, with the results showing that H(2) diffusion in Nafion
      membranes is nearly 1 order of magnitude faster than O(2) diffusion. The effects
      of water content and the concentration of adsorbed gases were verified, and a
      close correlation of Nafion free volume to gas transport properties was revealed.
      On the basis of the solution-diffusion mechanism, the permeabilities of H(2) and
      O(2) in hydrated Nafion membranes are calculated and compared with corresponding
      experiments, and the permeability of H(2) is found to be approximately twice that
      of O(2).

PMID- 21875105
TI  - Dilatational yielding of solid Langmuir monolayers.
AB  - In a previous work, Muruganathan and Fischer observed laser-induced local
      collapse of a methyl stearate monolayer. These experiments opened the possibility
      of studying the collapse mechanism in a highly controlled manner, since the laser
      intensity can be easily varied and collapse happens in a definite place (the
      laser focus). In this paper we extended the work presented by Muruganathan et
      al., describing the local yielding as an alternative pathway toward monolayer
      collapse competing with the global collapse of the monolayer. We first
      corroborated that the laser-induced collapse is a thermocapillary effect and
      afterward determined the threshold laser power necessary for the local pathway to
      win over the global collapse. We show that the laser threshold is determined more
      by the gradients in temperature and pressure than by the global pressure and
      temperature. We propose that the flow of material into the focus of the laser is
      observed after the yield stress of the monolayer is overcome. The higher the
      yield stress, the higher the temperature gradient that is necessary for the
      monolayer to yield. The local pathway opens only when the derivative of surface
      pressure with temperature is negative such that stress gradients point toward the
      laser focus and a sink of material is generated. In such a case we are able to
      give estimates of the dilatational yield pressure of the solid monolayer.

PMID- 21875106
TI  - Discovering the balance of steric and electronic factors needed to provide a new
      structural motif for photocatalytic hydrogen production from water.
AB  - Ru,Rh,Ru supramolecules are known to undergo multielectron photoreduction and
      reduce H(2)O to H(2). Ru,Rh bimetallics were recently shown to photoreduce but
      not catalyze H(2)O reduction. Careful tuning of sterics and electronics for
      [(TL)(2)Ru(dpp)RhCl(2)(TL')](3+) produce active bimetallic photocatalysts (TL =
      terminal ligand). The system with TL,TL' = Ph(2)phen photocatalytically reduces
      H(2)O to H(2) while TL,TL' = phen,bpy or bpy,(t)Bu(2)bpy do not.

PMID- 21875107
TI  - Identification of environmental reservoirs of nontyphoidal salmonellosis: aptamer
      assisted bioconcentration and subsequent detection of  salmonella  typhimurium by
      quantitative polymerase chain reaction.
AB  - In this study, identification of environmental reservoirs of  Salmonella enterica
      subsp.  enterica  serovar Typhimurium (abbreviated as  Salmonella  Typhimurium)
      in sediments, water, and aquatic flora collected from the Ganges River (Ganges
      riverine material) was carried out by adopting a two-step strategy. Step 1
      comprised a selective serovar-specific capture of  Salmonella  Typhimurium from
      potential reservoirs. Step 2 involved culture-free detection of selectively
      captured  Salmonella  Typhimurium by ttr gene-specific molecular beacon (MB)
      based quantitative polymerase chain reaction (q-PCR). The ttr gene-specific MB
      designed in this study could detect 1 colony-forming unit (cfu)/PCR captured by
      serovar-specific DNA aptamer. Sediments, water, and aquatic flora collected from
      the Ganges River were highly contaminated with  Salmonella  Typhimurium. The
      preanalytical step in the form of serovar-specific DNA aptamer-based biocapture
      of bacterial cells was found to enhance the sensitivity of the fluorescent probe
      in the presence of nonspecific DNA . Information about the presence of
      environmental reservoirs of  Salmonella  Typhimurium in the Ganges River region
      may pave the way for forecasting and management of nontyphoidal salmonellosis in
      south Asia.

PMID- 21875108
TI  - Aptamer functionalized microcantilever sensors for cocaine detection.
AB  - A cocaine-specific aptamer was used as a receptor molecule in a microcantilever
      based surface stress sensor for detection of cocaine molecules. An
      interferometric technique that relies on measuring differential displacement
      between two microcantilevers (a sensing/reference pair) was utilized to measure
      the cocaine/aptamer binding induced surface stress changes. Sensing experiments
      were performed for different concentrations of cocaine from 25 to 500 MUM in
      order to determine the sensor response as a function of cocaine concentration. In
      the lower concentration range from 25 to 100 MUM, surface stress values increased
      proportionally to coverage of aptamer/cocaine complexes from 11 to 26 mN/m.
      However, as the cocaine concentration was increased beyond 100 MUM, the surface
      stress values demonstrated a weaker dependence on the affinity complex surface
      coverage. On the basis of a sensitivity of 3 mN/m for the surface stress
      measurement, the lowest detectable threshold for the cocaine concentration is
      estimated to be 5 MUM. Sensing cantilevers could be regenerated and reused
      because of reversible thermal denaturation of aptamer.

PMID- 21875109
TI  - Photoinduced self-structured surface pattern on a molecular azo glass film:
      structure-property relationship and wavelength correlation.
AB  - In this study, three series of star-shaped molecular azo glasses were
      synthesized, and self-structured surface pattern formation on the azo compound
      films was studied by laser irradiation at different wavelengths. The molecular
      azo glasses were synthesized from three core precursors (Tr-AN, Tr-35AN, Tr
      H35AN), which were prepared by ring-opening reactions between 1,3,5-triglycidyl
      isocyanurate and corresponding aniline derivatives. The star-shaped azo compounds
      were obtained through azo-coupling reactions between the core precursors and
      diazonium salts of 4-chloroaniline, 4-aminobenzonitrile, and 4-nitroaniline,
      respectively. By using the two-step reaction scheme, three series of azo
      compounds with different structures were obtained. The core precursors and azo
      compounds were characterized by using (1)H NMR, FT-IR, UV-vis, mass spectrometry,
      and thermal analyses. The self-structured surface pattern formation on films of
      the azo compounds was studied by irradiating the azo compound films with a normal
      incident laser beam at different wavelengths (488, 532, and 589 nm). The results
      show that the photoinduced surface pattern formation behavior is closely related
      to the structure of the azo compounds, excitation wavelength, and light
      polarization conditions. The absorption band position of the pi-pi* transition is
      mainly determined by the electron-withdrawing groups on the azo chromophores.
      When the excitation wavelength is between lambda(max) and the band tail at the
      longer wavelength side, the self-structured surface patterns can be more
      efficiently induced to form on the films. The 3,5-dimethyl substitution on azo
      chromophores inhibits the surface pattern formation for certain excitation
      wavelengths. Increasing molecular interaction also shows an effect of restraining
      the surface pattern formation. The irradiations with linearly and circularly
      polarized light cause significant differences in the alignment manner of the
      pillarlike structures and their saturated height.

PMID- 21875110
TI  - Electroless silver plating of the surface of organic semiconductors.
AB  - The integration of nanoscale processes and devices demands fabrication routes
      involving rapid, cost-effective steps, preferably carried out under ambient
      conditions. The realization of the metal/organic semiconductor interface is one
      of the most demanding steps of device fabrication, since it requires mechanical
      and/or thermal treatments which increment costs and are often harmful in respect
      to the active layer. Here, we provide a microscopic analysis of a room
      temperature, electroless process aimed at the deposition of a nanostructured
      metallic silver layer with controlled coverage atop the surface of single
      crystals and thin films of organic semiconductors. This process relies on the
      reaction of aqueous AgF solutions with the nonwettable crystalline surface of
      donor-type organic semiconductors. It is observed that the formation of a uniform
      layer of silver nanoparticles can be accomplished within 20 min contact time. The
      electrical characterization of two-terminal devices performed before and after
      the aforementioned treatment shows that the metal deposition process is
      associated with a redox reaction causing the p-doping of the semiconductor.

PMID- 21875111
TI  - Water-soluble dual-emitting nanocrystals for ratiometric optical thermometry.
AB  - Multishell semiconductor nanocrystals have been synthesized that display
      intrinsic dual emission with robust photo and thermal stability and attractive
      thermal sensitivity. Dual emission is demonstrated following phase transfer into
      aqueous media. These nanocrystals are suitable for diverse optical thermometric
      or thermographic applications in biotechnology or other areas.

PMID- 21875112
TI  - Photocatalytic hydrogen evolution under highly basic conditions by using Ru
      nanoparticles and 2-phenyl-4-(1-naphthyl)quinolinium ion.
AB  - Photocatalytic hydrogen evolution with a ruthenium metal catalyst under basic
      conditions (pH 10) has been made possible for the first time by using 2-phenyl-4
      (1-naphthyl)quinolinium ion (QuPh(+)-NA), dihydronicotinamide adenine
      dinucleotide (NADH), and Ru nanoparticles (RuNPs) as the photocatalyst, electron
      donor, and hydrogen-evolution catalyst, respectively. The catalytic reactivity of
      RuNPs was virtually the same as that of commercially available PtNPs. Nanosecond
      laser flash photolysis measurements were performed to examine the photodynamics
      of QuPh(+)-NA in the presence of NADH. Upon photoexcitation of QuPh(+)-NA, the
      electron-transfer state of QuPh(+)-NA (QuPh(*)-NA(*+)) is produced, followed by
      formation of the pi-dimer radical cation with QuPh(+)-NA, [(QuPh(*)
      NA(*+))(QuPh(+)-NA)]. Electron transfer from NADH to the pi-dimer radical cation
      leads to the production of 2 equiv of QuPh(*)-NA via deprotonation of NADH(*+)
      and subsequent electron transfer from NAD(*) to QuPh(+)-NA. Electron transfer
      from the photogenerated QuPh(*)-NA to RuNPs results in hydrogen evolution even
      under basic conditions. The rate of electron transfer from QuPh(*)-NA to RuNPs is
      much higher than the rate of hydrogen evolution. The effect of the size of the
      RuNPs on the catalytic reactivity for hydrogen evolution was also examined by
      using size-controlled RuNPs. RuNPs with a size of 4.1 nm exhibited the highest
      hydrogen-evolution rate normalized by the weight of RuNPs.

PMID- 21875113
TI  - Assemblies of functional small-sized molecules having 4-amino-2,2,6,6
      tetramethylpiperidine-1-oxyl responsive to heat and pH in water and their water
      proton relaxivities.
AB  - 1,3,5-Triureabenzene derivatives carrying alkyl (C(n)) and poly(ethylene glycol)
      (Eg(m)) chains C(n)Eg(3) (1, 2, and 3, n = 6, 7, and 8, respectively) and
      C(n)N(X)Eg(m) (4 and 5, X = M (methyl), n = 6 and 8, respectively, m = 3; 6 and
      7, X = T (2,2,6,6-tetramethylpiperidine-1-oxyl, TEMPO), n = 6, m = 3 and 6,
      respectively) were prepared. All compounds in aqueous solutions exhibited the
      lower critical solution temperature (LCST) phenomena unique for small-sized
      molecules and formed self-assemblies above the transition temperature, T(t), of
      the LCST. Only compound 3 formed a hydrogel with a minimum gelation concentration
      of 0.5 mM (0.05 wt %). In 1.0 mM aqueous solution, the T(t) values were
      determined to be in the range of 12-40  degrees C. In addition, the T(t) values
      for 4-7 containing tertiary amine also responded to the solution pH with high
      sensitivity. The LCST behaviors for all compounds were reversible in the cycles
      of warming and cooling. The water proton relaxivities, r(1), for 6 and 7 carrying
      TEMPO were altered below and above T(t) and were largely reduced by the formation
      of self-assemblies above T(t). Compound 6 showed r(1) values at 25  degrees C of
      0.92 and 0.23 mM(-1) s(-1) at pH 7.0 and 6.0, respectively. In transmission
      electron microscopy (TEM) images, globular particles with polydispersity were
      observed, and their average hydrodynamic diameters (D(H)) were determined to be
      in the range of 2400-730 nm by dynamic light scattering. In the TEM and scanning
      electron microscopy images of a xerogel sample of 3, bundles of fibers with a
      diameter of ca. 10 nm and a network structure, respectively, were observed.

PMID- 21875115
TI  - Nonlinear optical processes in optically trapped InP nanowires.
AB  - We report on the observation of nonlinear optical excitation and related
      photoluminescence from single InP semiconductor nanowires held in suspension
      using a gradient force optical tweezers. Photoexcitation of free carriers is
      achieved through absorption of infrared (1.17 eV) photons from the trapping
      source via a combination of two- and three-photon processes. This was confirmed
      by power-dependent photoluminescence measurements. Marked differences in spectral
      features are noted between nonlinear optical excitation and direct excitation and
      are related to band-filling effects. Direct observation of second harmonic
      generation in trapped InP nanowires confirms the presence of nonlinear optical
      processes.

PMID- 21875114
TI  - Mitochondrial respiration inhibitors suppress protein translation and hypoxic
      signaling via the hyperphosphorylation and inactivation of translation initiation
      factor eIF2alpha and elongation factor eEF2.
AB  - Over 20,000 lipid extracts of plants and marine organisms were evaluated in a
      human breast tumor T47D cell-based reporter assay for hypoxia-inducible factor-1
      (HIF-1) inhibitory activity. Bioassay-guided isolation and dereplication-based
      structure elucidation of an active extract from the Bael tree (Aegle marmelos)
      afforded two protolimonoids, skimmiarepin A (1) and skimmiarepin C (2). In T47D
      cells, 1 and 2 inhibited hypoxia-induced HIF-1 activation with IC50 values of
      0.063 and 0.068 MUM, respectively. Compounds 1 and 2 also suppressed hypoxic
      induction of the HIF-1 target genes GLUT-1 and VEGF. Mechanistic studies revealed
      that 1 and 2 inhibited HIF-1 activation by blocking the hypoxia-induced
      accumulation of HIF-1alpha protein. At the range of concentrations that inhibited
      HIF-1 activation, 1 and 2 suppressed cellular respiration by selectively
      inhibiting the mitochondrial electron transport chain at complex I (NADH
      dehydrogenase). Further investigation indicated that mitochondrial respiration
      inhibitors such as 1 and rotenone induced the rapid hyperphosphorylation and
      inhibition of translation initiation factor eIF2alpha and elongation factor eEF2.
      The inhibition of protein translation may account for the short-term exposure
      effects exerted by mitochondrial inhibitors on cellular signaling, while the
      suppression of cellular ATP production may contribute to the inhibitory effects
      following extended treatment periods.

PMID- 21875116
TI  - Solvothermal synthesis of nanoporous polymer chalk for painting superhydrophobic
      surfaces.
AB  - Reported here is a facile synthesis of nanoporous polymer chalk for painting
      superhydrophobic surfaces. Taking this nanoporous polymer as a media,
      superhydrophobicity is rapidly imparted onto three typical kinds of substrates,
      including paper, transparent polydimethylsiloxane (PDMS), and finger skin.
      Quantitative characterization showed that the adhesion between the water droplet
      and polymer-coated substrates decreased significantly compared to that on the
      original surface, further indicating the effective wetting mode transformation.
      The nanoporous polymer coating would open a new door for facile, rapid, safe, and
      larger scale fabrication of superhydrophobic surfaces on general substrates.

PMID- 21875117
TI  - Generation of lambda/12 nanowires in chalcogenide glasses.
AB  - Nanowires have been widely studied and have gained a lot of interest in the past
      decade. Because of their high refractive index and high nonlinearity,
      chalcogenide glasses (ChGs) are a good candidate for the fabrication of photonic
      nanowires as such nanowaveguides provide the maximal confinement of light,
      enabling large enhancement of nonlinear interactions and group-velocity
      dispersion engineering. Here we report on the generation of lambda/12 (~68 nm)
      nanowires based on the theoretical and experimental study of the influence of the
      laser repetition rate on the direct laser fabrication in ChGs (lambda = 800 nm).
      Through a numerical model of cumulative heating, the optimum conditions for high
      resolution fabrication in As(2)S(3) are found. Nanowires with dimensions down to
      ~lambda/12 are for the first time successfully fabricated in ChGs. We show that
      the generated nanowires can be stacked to form a three-dimensional woodpile
      photonic crystal with a pronounced stop gap.

PMID- 21875118
TI  - Temperature and volume effect on the molecular dynamics of supercooled ibuprofen
      at ambient and elevated pressure.
AB  - In this paper we have studied the relative importance of thermal effects and
      volume in controlling structural relaxation of supercooled ibuprofen at ambient
      and elevated pressure. The relative contribution of both parameters on the
      structural relaxation times was estimated by means of the ratio E(V)/E(P) (i.e.,
      the activation energy at constant volume to enthalpy of activation at constant
      pressure), which can be simply estimated from dielectric relaxation and pressure
      volume-temperature (PVT) measurements. We found out that at ambient pressure the
      effect of thermal energy and molecular packing on structural relaxation dynamics
      is practically equaled. However, with increasing pressure the role of thermal
      effects in governing molecular dynamics becomes more prominent, leading to its
      complete domination in the pressure region of around 1 GPa. These results are
      discussed in the context of remarkably different behavior of supercooled
      ibuprofen crystallized at various thermodynamic conditions, as reported in our
      previous paper. The implication is that, when molecular mobility of supercooled
      ibuprofen is governed primarily by the thermal energy, significant slowing down
      of crystallization progress at isostructural relaxation conditions is observed.

PMID- 21875119
TI  - Molecular simulation study of the effect of various additives on salbutamol
      sulfate crystal habit.
AB  - The effects of polyvinylpyrrolidone (PVP), hydroxypropyl methyl cellulose (HPMC),
      and lecithin additives on salbutamol sulfate (SS) crystal growth are studied
      using molecular dynamics (MD) simulation, to provide an insight into the
      interaction between the additives and SS crystal faces at the atomistic level.
      The interaction energy between additives and crystal faces is presented. The
      intermolecular contacts between the additives and the crystal faces are analyzed
      by calculating the average number of contacts between O atoms of the additives
      and the H atoms of the first layer of the SS crystal. The mobility of each
      additive on SS crystal faces is also reported by determining the mean square
      displacement. Our results suggest that PVP is the most effective among the three
      additives for the inhibition of SS crystal growth. The methodology used in this
      study could be a powerful tool for selection of habit-modifying additives in
      other crystallization systems.

PMID- 21875121
TI  - Paracaseolide A, first alpha-alkylbutenolide dimer with an unusual tetraquinane
      oxa-cage bislactone skeleton from Chinese mangrove Sonneratia paracaseolaris.
AB  - A novel alpha-alkylbutenolide dimer, paracaseolide A (2), characterized by an
      unusual tetraquinane oxa-cage bislactone skeleton bearing two linear alkyl
      chains, was isolated from the mangrove plant Sonneratia paracaseolaris. The
      structure of 2 was elucidated by extensive spectroscopic analysis. A plausible
      retrosynthetic pathway for paracaseolide A (2) was proposed. Compound 2 exhibited
      significant inhibitory activity against dual specificity phosphatase CDC25B, a
      key enzyme for cell cycle progression, with an IC(50) value of 6.44 MUM.

PMID- 21875120
TI  - 18F-labeled modified porous silicon particles for investigation of drug delivery
      carrier distribution in vivo with positron emission tomography.
AB  - Because of its biocompatibility and ability to accommodate a variety of payloads
      from poorly soluble drugs to biomolecules, porous silicon (PSi) is a lucrative
      material for the development of carriers for particle-mediated drug delivery. We
      report a successful direct one-step (18)F-radiolabeling of three types of PSi
      microparticles, thermally hydrocarbonized THCPSi, thermally oxidized TOPSi, and
      thermally carbonized TCPSi for the investigation of their biodistribution in vivo
      with positron emission tomography as part of their evaluation as carriers for
      particle-mediated drug delivery. FTIR and XPS characterization of the PSi
      materials after carrier-added (18)F/(19)F-radiolabeling reveals that depending on
      the material the (18)F-labeling is likely to be accomplished either by
      substitution for surface silyl hydrogen or silyl fluoride or by nucleophilic
      attack of (18)F(-) to Si-O-Si bridges. With the selected (18)F-radiolabeling
      method, good to excellent in vitro radiolabel stability in simulated gastric and
      intestinal fluids and in plasma is achieved for all the particle types studied.
      Finally, a preliminary evaluation of (18)F-THCPSi microparticle biodistribution
      in the rat gastrointestinal tract after oral administration is reported,
      illustrating the utility of using (18)F-radiolabeled PSi as imaging probes for
      PSi-based drug delivery carrier distribution in vivo.

PMID- 21875122
TI  - Coumarin-Cu(II) ensemble-based cyanide sensing chemodosimeter.
AB  - An "ensemble"-based chemodosimeter 1-Cu(II) for cyanide detection is reported. 1
      Cu(II) can recognize a cyanide ion over other anionic species to show a marked
      fluorescence enhancement under aqueous conditions. "Off-on" fluorescence change
      of 1-Cu(II) is proceeded by addition of cyanide, which induces decomplexation of
      the Cu(II) ion from nonfluorescent 1 followed by hydrolytic cleavage of the
      resulted Schiff base to give a strongly fluorescent coumarinaldehyde (2). The
      selective detection of cyanide with 1-Cu(II) for biological application was also
      performed in HepG2 cells.

PMID- 21875123
TI  - Synthesis of alpha-S-glycosphingolipids based on uronic acids.
AB  - The synthesis of S-glycosphingolipids based on uronic acids is described. These
      compounds are analogous to the highly immunostimulatory antigens isolated from
      the cell walls of bacteria of the Sphingomonas family. Key to the synthetic route
      is a stereoselective anomerization to give alpha-glycosyl thiol precursors. A
      route to a sphinganine precursor from pseudoephedrine glycinamide is also
      described.

PMID- 21875124
TI  - Photostable dynamic rectification of one-dimensional schottky diode circuits with
      a ZnO nanowire doped by H during passivation.
AB  - For the first time, we demonstrated photostable and dynamic rectification in ZnO
      nanowire (NW) Schottky diode circuits where two diodes are face-to-face connected
      in the same ZnO wire. With their properties improved by H-doping from atomic
      layer deposited Al(2)O(3) passivation, our ZnO NW diode circuits stably operated
      at a maximum frequency of 100 Hz displaying a good rectification even under the
      lights. We thus conclude that our results promisingly appoached one-dimensional
      nanoelectronics.

PMID- 21875125
TI  - Catalytic enantioselective oxaziridination.
AB  - The first catalytic enantioselective synthesis of oxaziridines is presented. The
      oxidation of aryl and alkyl aldimines with m-CPBA under organocatalytic
      conditions using cinchona alkaloid-derived catalysts furnished optically active
      oxaziridines in good yields and high enantioselectivities (up to 94% ee).
      Mechanistic investigations indicate a stepwise enantioselective oxidation
      process.

PMID- 21875126
TI  - Use of solution-phase vibrational frequencies in continuum models for the free
      energy of solvation.
AB  - We find that vibrational contributions to a solute's free energy are in general
      insensitive to whether the solute vibrational frequencies are computed in the gas
      phase or in solution. In most cases, the difference is smaller than the intrinsic
      error in solvation free energies associated with the continuum approximation to
      solvation modeling, although care must be taken to avoid spurious results
      associated with limitations in the quantum-mechanical harmonic-oscillator
      approximation for very low-frequency molecular vibrations. We compute solute
      vibrational partition functions in aqueous and carbon tetrachloride solution and
      compare them to gas-phase molecular partition functions computed with the same
      level of theory and the same quasiharmonic approximation for the diverse and
      extensive set of molecules and ions included in the training set of the SMD
      continuum solvation model, and we find mean unsigned differences in vibrational
      contributions to the solute free energy of only about 0.2 kcal/mol. On the basis
      of these results and a review of the theory, we conclude, in contrast to previous
      work (Ho, J.; Klamt, H.; Coote, M. L. J. Phys. Chem. A 2010, 114, 13442), that
      using partition functions computed for molecules optimized in solution is a
      correct and useful approach for averaging over solute degrees of freedom when
      computing free energies of solutes in solution, and it is moreover recommended
      for cases where liquid and gas-phase solute structures differ appreciably or when
      stationary points present in liquid solution do not exist in the gas phase, for
      which we provide some examples. When gas-phase and solution-phase geometries and
      frequencies are similar, the use of gas-phase geometries and frequencies is a
      useful approximation.

PMID- 21875127
TI  - Expeditious synthesis of phenanthrenes via CuBr2-catalyzed coupling of terminal
      alkynes and N-tosylhydrazones derived from o-formyl biphenyls.
AB  - A new method for the synthesis of phenanthrenes via ligand-free CuBr(2)-catalyzed
      coupling/cyclization of terminal alkynes with N-tosylhydrazones derived from o
      formyl biphenyls has been developed. This new synthesis has wide range of
      functional group compatibility.

PMID- 21875128
TI  - Reshaping China's nuclear energy policy.

PMID- 21875129
TI  - Structure of DNA-cationic surfactant complexes at hydrophobically modified and
      hydrophilic silica surfaces as revealed by neutron reflectometry.
AB  - In this article, we discuss the structure and composition of mixed DNA-cationic
      surfactant adsorption layers on both hydrophobic and hydrophilic solid surfaces.
      We have focused on the effects of the bulk concentrations, the surfactant chain
      length, and the type of solid surface on the interfacial layer structure (the
      location, coverage, and conformation of the DNA and surfactant molecules).
      Neutron reflectometry is the technique of choice for revealing the surface layer
      structure by means of selective deuteration. We start by studying the interfacial
      complexation of DNA with dodecyltrimethylammonium bromide (DTAB) and
      hexadecyltrimethylammonium bromide (CTAB) on hydrophobic surfaces, where we show
      that DNA molecules are located on top of a self-assembled surfactant monolayer,
      with the thickness of the DNA layer and the surfactant-DNA ratio determined by
      the surface coverage of the underlying cationic layer. The surface coverages of
      surfactant and DNA are determined by the bulk concentration of the surfactant
      relative to its critical micelle concentration (cmc). The structure of the
      interfacial layer is not affected by the choice of cationic surfactant studied.
      However, to obtain similar interfacial structures, a higher concentration in
      relation to its cmc is required for the more soluble DTAB surfactant with a
      shorter alkyl chain than for CTAB. Our results suggest that the DNA molecules
      will spontaneously form a relatively dense, thin layer on top of a surfactant
      monolayer (hydrophobic surface) or a layer of admicelles (hydrophilic surface) as
      long as the surface concentration of surfactant is great enough to ensure a high
      interfacial charge density. These findings have implications for bioanalytical
      and nanotechnology applications, which require the deposition of DNA layers with
      well-controlled structure and composition.

PMID- 21875130
TI  - DNA zipper-based tweezers.
AB  - Here we report the design and development of DNA zippers and tweezers.
      Essentially a zipper system consists of a normal strand (N), a weak strand (W),
      and an opening strand (O). N strand is made up of normal DNA bases, while W is
      engineered to have inosine substituting for guanine. By altering the number and
      order of inosine, W is engineered to provide less than natural bonding affinities
      to N in forming the [N:W] helix. When O is introduced (a natural complement of
      N), it competitively displaces W from [N:W] and forms [N:O]. This principle is
      incorporated in the development of a molecular device that can perform the
      functions of tweezers (sense, hold, and release). Tweezers were constructed by
      holding N and W together using a hinge at one end. Thus, when the tweezers open,
      N and W remain in the same vicinity. This allows the tweezers to cycle among open
      and close positions by their opening and closing strands. Control over their
      opening and closing kinetics is demonstrated. In contrast to the previously
      reported DNA tweezers, the zipper mechanism makes it possible to operate them
      with opening strands that do not contain single-stranded DNA overhangs. Our
      approach yields a robust, compact, and regenerative tweezer system that could
      potentially be integrated into complex nanomachines.

PMID- 21875131
TI  - Directly drawing self-assembled, porous, and monolithic graphene fiber from
      chemical vapor deposition grown graphene film and its electrochemical properties.
AB  - Integration of graphene into macroscopic architectures represents the first step
      toward creating a new class of graphene-based nanodevices. We report a novel yet
      simple approach to fabricate graphene fibers, a porous and monolithic
      macrostructure, from chemical vapor deposition grown graphene films. Graphene is
      first self-assembled from a 2D film to a 1D fiberlike structure in an organic
      solvent (e.g., ethanol, acetone) and then dried to give the porous and crumpled
      structure. The method developed here is scalable and controllable, delivering
      tunable morphology and pore structure by controlling the evaporation of solvents
      with suitable surface tension. The fibers are 20-50 MUm thick, with a typical
      electrical conductivity of ~1000 S/m. The cyclic voltammetric studies show
      typical capacitive behavior for the porous graphene fibers with good rate
      stability and capacitance values ranging from 0.6 to 1.4 mF/cm(2). Decorated with
      only 1-3 wt % MnO(2), the graphene/MnO(2) composites exhibit remarkable
      enhancement of combined performance both with respect to discharge capacitance
      (up to 12.4 mF/cm(2)) and cycling stability. This special structure could
      facilitate chemical doping and electrochemical energy storage and find
      applications in catalyst supports, sensors, supercapacitors, Li ion batteries,
      etc.

PMID- 21875132
TI  - How does the urea dynamics differ from water dynamics inside the reverse micelle?
AB  - In this study, the urea dynamics inside AOT reverse micelle (RM) has been
      monitored without intervention of water using time-resolved fluorescence
      techniques from the picosecond to nanosecond time regime. It has been observed
      that urea dynamics inside the reverse micelle is severely retarded compared to
      water RM due to the formation of highly networked urea cluster inside the RM.
      Time-resolved fluorescence anisotropy study also confirms the existence of a
      confined environment around the dye at higher concentrations of urea inside the
      reverse micelle. The dynamics of urea-water mixtures inside AOT reverse micelle
      has also been monitored with increasing urea concentration to get insight about
      the effect of urea on the overall solvation dynamics feature. It has been
      observed that with the increase in urea concentration, the overall dynamics
      becomes slower, and it infers the presence of few water or urea molecules, those
      strongly associated with surrounding urea and (or) water by hydrogen bonds.

PMID- 21875133
TI  - Ordered complex nanostructures from bimodal self-assemblies of diblock copolymer
      micelles with solvent annealing.
AB  - We report the formation of ordered complex nanostructures from single-layered
      films of mixtures of polystyrene-poly(2-vinylpyridine) (PS-P2VP) and polystyrene
      poly(4-vinylpyridine) (PS-P4VP) diblock copolymer micelles by THF
      (tetrahydrofuran) annealing. We first examined the influence of THF vapor on PS
      P2VP and PS-P4VP micelles in their single-layered films. Due to the different
      solubility of PS-P2VP and PS-P4VP copolymers in THF, a hexagonal array of PS-P2VP
      micelles was changed into cylindrical nanodomains, but that of PS-P4VP micelles
      was not changed. The different influence of THF on PS-P2VP and PS-P4VP micelles
      was combined in single-layered films of mixtures of both micelles. For the
      purpose, we prepared mixture solutions of independently prepared small PS-P2VP
      and large PS-P4VP micelles. Then, bimodal self-assemblies of micelles were
      prepared from the mixtures, for which the hexagonal array of large PS-P4VP
      micelles was surrounded by small PS-P2VP micelles. When the bimodal self-assembly
      was annealed by THF vapor, PS-P2VP micelles were transformed into cylindrical
      nanodomains, but their reorganization was guided by hexagonally arranged PS-P4VP
      micelles. As a result, we were able to produce ordered complex nanostructures in
      the form of a hexagonal array of PS-P4VP micelles surrounded by PS-P2VP
      cylinders, which was further utilized for the synthesis of Au nanoparticles.

PMID- 21875134
TI  - Relationship between structural gel and mechanical gel for ABA triblock copolymer
      in solutions: a molecular dynamics simulation.
AB  - Polymer gel exists ubiquitously in our daily life, as in food, cosmetics, drugs,
      and so on. From the structural point of view, the 3D network can be found in a
      structural gel. In most experimental work, the gel is identified by the sharp
      increase in modules; that is, the gel should have similar properties as those of
      a solid, which is named as mechanical gel. However, not all structural gels have
      strong mechanical responses. Therefore, studying the relationship between
      structural gel and mechanical gel is very important. In this work, we investigate
      the structure and mechanical properties of symmetric ABA copolymers with
      solvophobic end blocks during the sol-gel transition. Three typical systems with
      weak, middle, and strong solvophobicities are simulated. It is found that the
      gelation concentration, gel structure, and mechanical response of structural gel
      are strongly affected by the solvophobicity of ABA block copolymer. We also find
      that only the gel formed in strong solvophobic systems has a strong mechanical
      response. Furthermore, the influence of solvophobicity of A-block on the static
      and dynamic properties of ABA block copolymers in solutions is also studied to
      give a molecular understanding of physical gelation.

PMID- 21875135
TI  - Gold-catalyzed tandem 1,3-migration/[2 + 2] cycloaddition of 1,7-enyne benzoates
      to azabicyclo[4.2.0]oct-5-enes.
AB  - A synthetic method that relies on gold(I)-catalyzed tandem 1,3-migration/[2 + 2]
      cycloaddition of 1,7-enyne benzoates to prepare azabicyclo[4.2.0]oct-5-enes is
      described.

PMID- 21875136
TI  - Temporary anion states of pyrimidine and halopyrimidines.
AB  - The empty-level electronic structures of pyrimidine and its 2-chloro, 2-bromo,
      and 5-bromo derivatives have been studied with electron transmission spectroscopy
      (ETS) and dissociative electron attachment spectroscopy (DEAS) in the 0-5 eV
      energy range. The spectral features were assigned to the corresponding anion
      states with the support of theoretical calculations at the ab initio and density
      functional theory levels. The empty orbital energies obtained by simple Koopmans'
      theorem calculations, scaled with empirical equations, quantitatively reproduced
      the energies of vertical electron attachment to pi* and sigma* empty orbitals
      measured in the ET spectra and predicted vertical electron affinities close to
      zero for the three halo derivatives. The total anion currents of the halo
      derivatives, measured at the walls of the collision chamber as a function of the
      impact electron energy, presented intense maxima below 0.5 eV. The mass-selected
      spectra showed that, in this energy, range the total anion current is essentially
      due to halide fragment anions. The DEA cross sections of the bromo derivatives
      were found to be about six times larger than that of the chloro derivative. The
      absolute cross sections at incident electron energies close to zero were
      evaluated to be 10(-16)-10(-15) cm(2).

PMID- 21875137
TI  - Layered-metal-hydroxide nanosheet arrays with controlled nanostructures to assist
      direct electronic communication at biointerfaces.
AB  - In this work, ordered vertical arrays of layered double hydroxide (LDH)
      nanosheets have been developed to achieve electron transfer (eT) at biointerfaces
      in electrochemical devices. It is found that tailoring the gap size of LDH
      nanosheet arrays could significantly promote the eT rate. This research has
      successfully extended nanomaterials for efficient modifications of electrode
      surfaces from nanoparticles, nanowires, nanorods, and nanotubes to nanosheets.

PMID- 21875138
TI  - Rapid NMR method for the quantification of organic compounds in thin stillage.
AB  - Thin stillage contains organic and inorganic compounds, some of which may be
      valuable fermentation coproducts. This study describes a thorough analysis of the
      major solutes present in thin stillage as revealed by NMR and HPLC. The
      concentration of charged and neutral organic compounds in thin stillage was
      determined by excitation sculpting NMR methods (double pulse field gradient spin
      echo). Compounds identified by NMR included isopropanol, ethanol, lactic acid,
      1,3-propanediol, acetic acid, succinic acid, glycerophosphorylcholine, betaine,
      glycerol, and 2-phenylethanol. The concentrations of lactic and acetic acid
      determined with NMR were comparable to those determined using HPLC. HPLC and NMR
      were complementary, as more compounds were identified using both methods. NMR
      analysis revealed that stillage contained the nitrogenous organic compounds
      betaine and glycerophosphorylcholine, which contributed as much as 24% of the
      nitrogen present in the stillage. These compounds were not observed by HPLC
      analysis.

PMID- 21875139
TI  - Pyridinyl directed alkenylation with olefins via Rh(III)-catalyzed C-C bond
      cleavage of secondary arylmethanols.
AB  - Novel C-C bond cleavage of secondary alcohols through Rh(III)-catalyzed beta
      carbon elimination directed by a pyridinyl group is reported. A five-membered
      rhodacycle is proposed as a key intermediate, which undergoes further
      alkenylation with various olefins. This novel transformation shows high
      efficiency along with excellent selectivity in mild conditions. A wide range of
      functionalities are compatible. This study offers a new strategy to carry out C-C
      bond activation.

PMID- 21875140
TI  - Combined approach using ligand efficiency, cross-docking, and antitarget hits for
      wild-type and drug-resistant Y181C HIV-1 reverse transcriptase.
AB  - New hits against HIV-1 wild-type and Y181C drug-resistant reverse transcriptases
      were predicted taking into account the possibility of some of the known
      metabolism interactions. In silico hits against a set of antitargets (i.e.,
      proteins or nucleic acids that are off-targets from the desired pharmaceutical
      target objective) are used to predict a simple, visual measure of possible
      interactions for the ligands, which helps to introduce early safety
      considerations into the design of compounds before lead optimization. This
      combined approach consists of consensus docking and scoring: cross-docking to a
      group of wild-type and drug-resistant mutant proteins, ligand efficiency (also
      called binding efficiency) indices as new ranking measures, pre- and postdocking
      filters, a set of antitargets and estimation, and minimization of atomic clashes.
      Diverse, small-molecule compounds with new chemistry (such as a triazine core
      with aromatic side chains) as well as known drugs for different applications
      (oxazepam, chlorthalidone) were highly ranked to the targets having binding
      interactions and functional group spatial arrangements similar to those of known
      inhibitors, while being moderate to low binders to the antitargets. The results
      are discussed on the basis of their relevance to medicinal and computational
      chemistry. Optimization of ligands to targets and off-targets or antitargets is
      foreseen to be critical for compounds directed at several simultaneous sites.

PMID- 21875141
TI  - Insights into molecular basis of cytochrome p450 inhibitory promiscuity of
      compounds.
AB  - Cytochrome P450 inhibitory promiscuity of a drug has potential effects on the
      occurrence of clinical drug-drug interactions. Understanding how a molecular
      property is related to the P450 inhibitory promiscuity could help to avoid such
      adverse effects. In this study, an entropy-based index was defined to quantify
      the P450 inhibitory promiscuity of a compound based on a comprehensive data set,
      containing more than 11,500 drug-like compounds with inhibition against five
      major P450 isoforms, 1A2, 2C9, 2C19, 2D6, and 3A4. The results indicated that the
      P450 inhibitory promiscuity of a compound would have a moderate correlation with
      molecular aromaticity, a minor correlation with molecular lipophilicity, and no
      relations with molecular complexity, hydrogen bonding ability, and TopoPSA. We
      also applied an index to quantify the susceptibilities of different P450 isoforms
      to inhibition based on the same data set. The results showed that there was a
      surprising level of P450 inhibitory promiscuity even for substrate specific P450,
      susceptibility to inhibition follows the rank-order: 1A2 > 2C19 > 3A4 > 2C9 >
      2D6. There was essentially no correlation between P450 inhibitory potency and
      specificity and minor negative trade-offs between P450 inhibitory promiscuity and
      catalytic promiscuity. In addition, classification models were built to predict
      the P450 inhibitory promiscuity of new chemicals using support vector machine
      algorithm with different fingerprints. The area under the receiver operating
      characteristic curve of the best model was about 0.9, evaluated by 5-fold cross
      validation. These findings would be helpful for understanding the mechanism of
      P450 inhibitory promiscuity and improving the P450 inhibitory selectivity of new
      chemicals in drug discovery.

PMID- 21875142
TI  - Charge density analysis of 2-methyl-4-nitro-1-phenyl-1H-imidazole-5-carbonitrile:
      an experimental and theoretical study of C=N...C=N interactions.
AB  - The experimental charge density distribution was determined for 2-methyl-4-nitro
      1-phenyl-1H-imidazole-5-carbonitryle, using the Hansen-Coppens multipole model.
      Free R factor calculations were performed with MoPro software to find optimal
      restraints for a physically meaningful model. The crystal packing is determined
      to some extent by weak C-H...O and C-H...N hydrogen bonds but mostly by a lateral
      electrostatic interaction between antiparallel side-by-side C=N groups.
      Electrostatic energy calculations were performed based on the experimental data
      and are in line with the high-level, explicitly correlated theoretical SCS-RI-MP2
      F12 calculations of total energy. The molecular dipole moment and atomic charge
      values were compared for different experimental and theoretical models, to
      highlight the dependence of the electrostatic property outputs on the applied
      restraints. Interesting O...O contacts are also described. The results are
      compared with two recently investigated nitroimidazole derivatives, namely, 1-(2'
      aminophenyl)-2-methyl-4-nitroimidazole and 1-phenyl-4-nitroimidazole.

PMID- 21875143
TI  - Magnetic and fluorescent glycopolymer hybrid nanoparticles for intranuclear
      optical imaging.
AB  - The synthesis of galactose-displaying core-shell nanospheres exhibiting both
      fluorescent and magnetic properties by grafting a glycocopolymer consisting of 6
      O-methacryloylgalactopyranose (MAGal) and 4-(pyrenyl)butyl methacrylate (PyMA)
      onto magnetic silica particles via thiol-ene chemistry is reported. Magnetization
      measurements indicated that neither the encapsulation of the iron oxide particles
      into silica nor the grafting of the glycocopolymer chains had a significant
      influence on the superparamagnetic properties. This not only simplifies the
      purification of the particles but may facilitate the use of the particles in
      applications such as hyperthermia or magnetic resonance imaging (MRI).
      Furthermore, the hydrophilic glycopolymer shell provided solubility of the
      particles in aqueous medium and enabled the uptake of the particles into the
      cytoplasm and nucleus of lung cancer cells via carbohydrate-lectin recognition
      effects.

PMID- 21875144
TI  - Morphological effects on surface-enhanced Raman scattering from silver butterfly
      wing scales synthesized via photoreduction.
AB  - Through a simple room-temperature photoreduction process, this letter conformally
      replicates 3D submicrometer structures of wing scales from two butterfly species
      into Ag to generate practical surface-enhanced Raman scattering (SERS)
      substrates. The Ag replicas of butterfly scales with higher structural
      periodicity are able to detect rhodamine 6G at a low concentration down to 10(-9)
      M, which is three orders of magnitude lower than the detectable concentration
      limit of using quasi-periodic Ag butterfly structures. This result presents a way
      to select suitable scale morphologies from 174,500 species of Lepidopterans to
      replicate, as consumable SERS substrates with low cost and high reproducibility.

PMID- 21875146
TI  - Rhodium-catalyzed, efficient deutero- and tritiosilylation of carbonyl compounds
      from hydrosilanes and deuterium or tritium.
AB  - A cationic rhodium compound which is an active catalyst for both the hydrogen
      isotope exchange in hydrosilanes and the hydrosilylation of carbonyl compounds
      permits, in a one-flask, two-step procedure, efficient deutero- and
      tritiosilylations using SiEt(3)H under D(2) (0.5 bar) or T(2), at low catalyst
      loadings (0.1-0.5 mol %).

PMID- 21875147
TI  - Vocabulary of definitions of life suggests a definition.
AB  - Analysis of the vocabulary of 123 tabulated definitions of life reveals nine
      groups of defining terms (definientia) of which the groups (self-)reproduction
      and evolution (variation) appear as the minimal set for a concise and inclusive
      definition: Life is self-reproduction with variations.

PMID- 21875148
TI  - Terpyridine platinum(II) complexes inhibit cysteine proteases by binding to
      active-site cysteine.
AB  - Platinum(II) complexes have been demonstrated to form covalent bonds with sulfur
      donating ligands (in glutathione, metallothionein and other sulfur-containing
      biomolecules) or coordination bonds with nitrogen-donating ligands (such as
      histidine and guanine). To investigate how these compounds interact with cysteine
      proteases, we chose terpyridine platinum(II) (TP-Pt(II)) complexes as a model
      system. By using X-ray crystallography, we demonstrated that TP-Pt(II) formed a
      covalent bond with the catalytic cysteine residue in pyroglutamyl peptidase I.
      Moreover, by using MALDI (matrix-assisted laser desorption/ionization) and TOF
      TOF (time of flight) mass spectrometry, we elucidated that the TP-Pt(II) complex
      formed a covalent bond with the active-site cysteine residue in two other types
      of cysteine protease. Taken together, the results unequivocally showed that TP
      Pt(II) complexes can selectively bind to the active site of most cysteine
      proteases. Our findings here can be useful in the design of new anti-cancer, anti
      parasite or anti-virus platinum(II) compounds.

PMID- 21875149
TI  - Biological evaluation and interaction of a newly designed anti-cancer Pd(II)
      complex and human serum albumin.
AB  - The pharmacokinetics and pharmacodynamics of any drug will depend, largely, on
      the interaction that has with human serum albumin (HSA), the most abundant plasma
      protein. The interaction between newly synthesized Pd(II) complexe, 2,2'
      bipyridin Butylglycinato Pd(II) nitrate, an anti-tumor component, with HSA was
      studied at different temperatures by fluorescence, far UV circular dichroism
      (CD), UV-visible spectrophotometry and theoretical approaches. The Pd(II) complex
      has a strong ability to quench the intrinsic fluorescence of HSA through a
      dynamic quenching procedure. The binding parameters and thermodynamic parameters,
      including deltaH degrees , deltaS degrees  and deltaG degrees  were calculated by
      fluorescence quenching method, indicated that hydrophobic forces play a major
      role in the interaction of Pd(II) complex with HSA. Based on Autodock, FRET
      (fluorescence resonance energy transfer) and fluorescence quenching data, it may
      be concluded that one of the binding sites in the complex of HSA is near the only
      one Trp of HSA (Trp214) in sub domain IIA of the protein. Far-UV-CD results
      indicated that Pd(II)-complex induced increase in the alpha-helical content of
      the protein. The anti-tumor property of the synthesized Pd(II) complex was
      studied by testing it on human tumor cell line K562. The 50% cytotoxic
      concentration (Cc50) of complex was determined using MTT (3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyl tetrazolium bromide) assay. Also, fluorescence staining with
      DAPI (4,6-diamidino-2-phenylindole) revealed some typical nuclear changes that
      are characteristic of apoptosis which is induced at Cc50 concentration of Pd(II)
      complex in K562 cell line after 24 h incubation. Our results suggest that Pd(II)
      complex is a promising anti-proliferative agent and should execute its biological
      effects by inducing apoptosis.

PMID- 21875150
TI  - Molecular modeling and molecular dynamics simulation studies of Delta-Notch
      complex.
AB  - Notch is a single-pass transmembrane receptor protein which is composed of a
      short extracellular region, a single-pass transmembrane domain and a small
      intracellular region. Notch ligand like Delta, member of the DSL protein family,
      is also single-pass transmembrane protein. It has been demonstrated that of the
      36 EGF repeats of Notch, 11th and 12th are sufficient to mediate interactions
      with Delta. Crystal structure of mammalian Notch extracellular ligand binding
      domain contains 11 and 12 EGF-like repeats. Here a portion of the Delta protein
      of Drosophila, known to interact with Notch extracellular domain (ECD) has been
      modeled using homology modeling. The structure of the Delta-Notch complex was
      subsequently modeled by protein docking method using GRAMM. MD simulations of the
      modeled structures were performed. The structure for Delta-Notch complex has been
      proposed based on interaction energy parameter and planarity studies.

PMID- 21875151
TI  - Insight into the inhibitory mechanism and binding mode between D77 and HIV-1
      integrase by molecular modeling methods.
AB  - Integrase is an essential enzyme in the life cycle of Human immunoficiency virus
      type 1 (HIV-1) and also an important target for designing integrase inhibitors.
      In this paper, the binding modes between the wild type integrase core domain
      (ICD) and the W131A mutant ICD with the benzoic acid derivative--D77 were
      investigated using the molecular docking combined with molecular dynamics (MD)
      simulations. The result of MD simulations showed that the W131A substitution
      affected the flexibility of the region 150-167 in both the monomer A and B of the
      mutant type ICD. In principle, D77 interacted with the residues around the Lens
      Epithelium-Derived Growth Factor (LEDGF/p75) binding site which is nearby the HIV
      1 integrase dimer interface. However, the specific binding modes for D77-wild
      type integrase and D77-mutant integrase systems are various. According to the
      binding mode of D77 with the wild type ICD, D77 can effectively intervene with
      the binding of LEDGF/p75 to integrase due to a steric hindrance effect around the
      LEDGF/p75 binding site. In addition, we found that D77 might also affect its
      inhibitory action by reducing the flexibility of the region 150-167 of integrase.
      Through energy decomposition calculated with the Molecular Mechanics Generalized
      Born Surface Area approach to estimate the binding affinity, it seems likely that
      W131 and E170 are indispensable for the ligand binding, as characterized by the
      largest binding affinity. All the above results are consistent with the
      experimental data, providing us with some helpful information not only for the
      understanding of the mechanism of this kind of inhibitor but also for the
      rational drug design.

PMID- 21875152
TI  - Search for novel remedies to augment radiation resistance of inhabitants of
      Fukushima and Chernobyl disasters: identifying DNA repair protein XRCC4
      inhibitors.
AB  - Two nuclear plant disasters occurring within a span of 25 years threaten health
      and genome integrity both in Fukushima and Chernobyl. Search for remedies capable
      of enhancing DNA repair efficiency and radiation resistance in humans appears to
      be a urgent problem for now. XRCC4 is an important enhancer in promoting repair
      pathway triggered by DNA double-strand break (DSB). In the context of radiation
      therapy, active XRCC4 could reduce DSB-mediated apoptotic effect on cancer cells.
      Hence, developing XRCC4 inhibitors could possibly enhance radiotherapy outcomes.
      In this study, we screened traditional Chinese medicine (TCM) database, TCM
      Database@Taiwan, and have identified three potent inhibitor agents against XRCC4.
      Through molecular dynamics simulation, we have determined that the protein-ligand
      interactions were focused at Lys188 on chain A and Lys187 on chain B.
      Intriguingly, the hydrogen bonds for all three ligands fluctuated frequently but
      were held at close approximation. The pi-cation interactions and ionic
      interactions mediated by o-hydroxyphenyl and carboxyl functional groups
      respectively have been demonstrated to play critical roles in stabilizing binding
      conformations. Based on these results, we reported the identification of
      potential radiotherapy enhancers from TCM. We further characterized the key
      binding elements for inhibiting the XRCC4 activities.

PMID- 21875153
TI  - Energetics of hydrogen bond switch, residue burial and cavity analysis reveals
      molecular basis of improved heparin binding to antithrombin.
AB  - Antithrombin III (ATIII) is the main inhibitor of the coagulation proteases like
      factor Xa and thrombin. Anticoagulant activity of ATIII is increased by several
      thousand folds when activated by vascular wall heparan sulfate proteoglycans
      (HSPGs) and pharmaceutical heparins. ATIII isoforms in human plasma, alpha-ATIII
      and beta-ATIII differ in the amount of glycosylation which is the basis of
      differences in their heparin binding affinity and function. Crystal structures
      and site directed mutagenesis studies have mapped the heparin binding site in
      ATIII, however the hydrogen bond switch and energetics of interaction during the
      course of heparin dependent conformational change remains largely unclear. An
      analysis of heparin bound conformational states of ATIII using PEARLS software
      showed that in heparin bound intermediate state, Arg 47 and Arg 13 residues make
      hydrogen bonds with heparin but in the activated conformation Lys 11 and Lys 114
      have more hydrogen bond interactions. In the protease bound-antithrombin
      pentasaccharide complex Lys 114, Pro 12 and Lys 125 form important hydrogen
      bonding interactions. The results showed that A-helix and N-terminal end residues
      are more important in the initial interactions but D-helix is more important
      during the latter stage of conformational activation and during the process of
      protease inhibition. We carried out the residue wise Accessible Surface Area
      (ASA) analysis of alpha and beta ATIII native states and the results indicated
      major differences in burial of residues from Ser 112 to Ser 116 towards the N
      terminal end. This region is involved in the P-helix formation on account of
      heparin binding. A cavity analysis showed a progressively larger cavity formation
      during activation in the region just adjacent to the heparin binding site towards
      the C-terminal end. We hypothesize that during the process of conformational
      change after heparin binding beta form of antithrombin has low energy barrier to
      form D-helix extension toward N and C-terminal end as compared to alpha isoform.

PMID- 21875154
TI  - Molecular modeling studies of Yersinia pestis dihydrofolate reductase.
AB  - Considering the risk represented by plague today as a potential biological
      warfare agent, we propose cytosolic Yersinia pestis dihydrofolate reductase
      (YpDHFR) as a new target to the design of selective plague chemotherapy. This
      enzyme has a low homology with the human enzyme and its crystallographic
      structure has been recently deposited in the Protein Data Bank (PDB). Comparisons
      of the docking energies and molecular dynamic behaviors of five known DHFR
      inhibitors inside a 3D model of YpDHFR (adapted from the crystallographic
      structure) and human DHFR (HssDHFR), revealed new potential interactions and
      suggested insights into the design of more potent HssDHFR inhibitors as well as
      selective inhibitors for YpDHFR.

PMID- 21875155
TI  - The structural stability of wild-type horse prion protein.
AB  - Prion diseases (e.g. Creutzfeldt-Jakob disease (CJD), variant CJD (vCJD),
      Gerstmann-Straussler-Scheinker syndrome (GSS), Fatal Familial Insomnia (FFI) and
      Kuru in humans, scrapie in sheep, bovine spongiform encephalopathy (BSE or 'mad
      cow' disease) and chronic wasting disease (CWD) in cattles) are invariably fatal
      and highly infectious neurodegenerative diseases affecting humans and animals.
      However, by now there have not been some effective therapeutic approaches or
      medications to treat all these prion diseases. Rabbits, dogs, and horses are the
      only mammalian species reported to be resistant to infection from prion diseases
      isolated from other species. Recently, the beta2-alpha2 loop has been reported to
      contribute to their protein structural stabilities. The author has found that
      rabbit prion protein has a strong salt bridge ASP177-ARG163 (like a taut bow
      string) keeping this loop linked. This paper confirms that this salt bridge also
      contributes to the structural stability of horse prion protein. Thus, the region
      of beta2-alpha2 loop might be a potential drug target region. Besides this very
      important salt bridge, other four important salt bridges GLU196-ARG156-HIS187,
      ARG156-ASP202 and GLU211-HIS177 are also found to greatly contribute to the
      structural stability of horse prion protein. Rich databases of salt bridges,
      hydrogen bonds and hydrophobic contacts for horse prion protein can be found in
      this paper.

PMID- 21875156
TI  - Prevalent mutations of human prion protein: a molecular modeling and molecular
      dynamics study.
AB  - Point mutations in the human prion protein gene, leading to amino acid
      substitutions in the human prion protein contribute to conversion of PrPC to
      PrPSc and amyloid formation, resulting in prion diseases such as familial
      Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease (GSS),
      and fatal familial insomnia. We have investigated impressions of prevalent
      mutations including Q217R, D202N, F198S, on the human prion protein and compared
      the mutant models with wild types. Structural analyses of models were performed
      with molecular modeling and molecular dynamics simulation methods. According to
      our results, frequently occurred mutations are observed in conserved and fully
      conserved sequences of human prion protein and the most fluctuation values occur
      in the Helix 1 around residues 144-152 and C-terminal end of the Helix 2. Our
      analysis of results obtained from MD simulation clearly shows that this long
      range effect plays an important role in the conformational fluctuations in mutant
      structures of human prion protein. Results obtained from molecular modeling such
      as creation or elimination of some hydrogen bonds, increase or decrease of the
      accessible surface area and molecular surface, loss or accumulation of negative
      or positive charges on specific positions, and altering the polarity and pKa
      values, show that amino acid point mutations, though not urgently change the
      stability of PrP, might have some local impacts on the protein interactions which
      are required for oligomerization into fibrillar species.

PMID- 21875157
TI  - Gene re-annotation in genome of the extremophile Pyrobaculum aerophilum by using
      bioinformatics methods.
AB  - In this paper, we re-annotated the genome of Pyrobaculum aerophilum str. IM2,
      particularly for hypothetical ORFs. The annotation process includes three parts.
      Firstly and most importantly, 23 new genes, which were missed in the original
      annotation, are found by combining similarity search and the ab initio gene
      finding approaches. Among these new genes, five have significant similarities
      with function-known genes and the rest have significant similarities with
      hypothetical ORFs contained in other genomes. Secondly, the coding potentials of
      the 1645 hypothetical ORFs are re-predicted by using 33 Z curve variables
      combined with Fisher linear discrimination method. With the accuracy being
      99.68%, 25 originally annotated hypothetical ORFs are recognized as non-coding by
      our method. Thirdly, 80 hypothetical ORFs are assigned with potential functions
      by using similarity search with BLAST program. Re-annotation of the genome will
      benefit related researches on this hyperthermophilic crenarchaeon. Also, the re
      annotation procedure could be taken as a reference for other archaeal genomes.
      Details of the revised annotation are freely available at
      http://cobi.uestc.edu.cn/resource/paero/

PMID- 21875158
TI  - Role of ligand binding in structural organization of add A-riboswitch aptamer: a
      molecular dynamics simulation.
AB  - The specific binding of ligands is the first step of gene expression or
      translation regulation by riboswitches. However, understanding the mechanism of
      the specific binding is still difficult because the tertiary structures of the
      riboswitch aptamers are available almost only for ligand-bound state at present.
      In this paper we hope to give some insights into this problem through the studies
      of the role of ligand-aptamer interaction in the structural organization of add A
      riboswitch aptamer, based on the crystal structure of the ligand-bound aptamer.
      We use all-atom molecular dynamics to simulate the behaviors of the aptamer in
      ligand-bound, free and mutated states by Amber force field. The results show that
      the correct paring of the ligand adenine with the nucleotide U74 in the binding
      pocket is crucial to stabilizing the conformations of the ligand-bound aptamer,
      especially the helix P1 connecting the expression platform. Our results also
      suggest that both the nucleotide U74 and U51 may be the key sites of the ligand
      recognition but the former has much higher probability as the initial docking
      site. This is in agreement with previous experimental results.

PMID- 21875159
TI  - OnionTree XML: a format to exchange gene-related probabilities.

PMID- 21875160
TI  - Excess costs associated with patients with pulmonary arterial hypertension in a
      US privately insured population.
AB  - BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare but fatal disease.
      Little is known about the economic burden associated with PAH patients in the US.
      OBJECTIVES: The objective of this study was to estimate excess direct costs
      associated with privately insured PAH patients in the US. METHODS: From a
      privately insured claims database (>8 million beneficiaries, 2002-7), 471
      patients with PAH were identified using the criteria: two or more claims for
      primary pulmonary hypertension (PH), International Classification of Diseases,
      ninth edition, clinical modification (ICD-9-CM) code 416.0; no left heart
      disease, lung diseases, chronic thromboembolic PH or miscellaneous PH diagnoses
      within 12 months prior or 1 month after the initial PH claim (index date); one or
      more claim for right heart catheterization (RHC) within 6 months prior to any PH
      claim or one or more claim for echocardiogram within 6 months prior to a
      specialist-diagnosed PH claim; aged 18-64 years. Patients with PAH were matched
      demographically to controls without PH. Patients were followed as long as
      continuously eligible; mean follow-up of PAH patients was 24.8 months. Chi
      squared tests were used to compare baseline co-morbidities. Wilcoxon rank-sum
      tests were used to compare direct (medical and pharmaceutical) patient-month
      costs to insurers. RESULTS: The average age for PAH patients was 52.2 years, and
      55.8% were women. Compared with controls, PAH patients had significantly higher
      baseline rates of co-morbidities (e.g. essential hypertension, diabetes mellitus
      and congestive heart failure) and a higher mean Charlson Co-morbidity Index
      score. Mean direct patient-month costs (year 2007 values) were $US2023 for PAH
      patients and $US498 for controls (p < 0.0001), yielding excess costs of $US1525.
      Sensitivity analysis restricting the sample to patients diagnosed following RHC
      yielded a 64% increase in excess costs relative to the original sample. Regarding
      cost drivers, inpatient services accounted for 45%, outpatient and other services
      for 38% and prescription drugs for 15% of total direct healthcare costs per
      patient-month in PAH patients. Circulatory/respiratory system-related patient
      month costs were $US724 among PAH patients and $US114 among controls (p <
      0.0001). CONCLUSIONS: Patients with PAH had substantially higher costs and co
      morbidity than controls, with circulatory/respiratory system-related costs
      accounting for 40% of excess costs. The high burden of illness suggests
      opportunities for savings from improved management.

PMID- 21875161
TI  - Cost effectiveness of chemoprevention for prostate cancer with dutasteride in a
      high-risk population based on results from the REDUCE clinical trial.
AB  - BACKGROUND: The REDUCE trial examined whether chemoprevention with the dual 5
      alpha reductase inhibitor, dutasteride, reduced risk of prostate cancer (PCa)
      detection on biopsy. OBJECTIVE: We examined the cost effectiveness of dutasteride
      compared with placebo in preventing PCa in men at increased risk as seen in
      REDUCE, from a US payer perspective. METHODS: A Markov model was developed to
      compare costs and outcomes of chemoprevention with dutasteride 0.5 mg/day or
      placebo with usual care in men aged 50-75 years, with serum prostate-specific
      antigen (PSA) of 2.5-10 ng/mL (men aged <60 years) or 3.0-10 ng/mL (men aged >=60
      years), and with a single negative prostate biopsy in the prior 6 months. The
      model simulated the REDUCE cohort annually through different health states over 4
      , 10-year and lifetime time horizons. Risks of PCa for men receiving placebo and
      dutasteride were obtained from REDUCE. Rates of acute urinary retention events
      and benign prostate hyperplasia-related surgeries also came from REDUCE. Costs
      and utilities were obtained from published literature. All costs are reported in
      $US, year 2009 values. RESULTS: The model indicated that, over 10 years,
      dutasteride patients would experience fewer PCas (251 vs 312 per 1000 patients)
      at increased cost ($US15 341 vs $US12 316) than placebo patients. Although life
      years were not substantially affected, the model calculated an increase in QALYs
      of 0.14 for dutasteride patients. Chemoprevention with dutasteride appeared to be
      cost effective, with an incremental cost per QALY of $US21 781 and cost per PCa
      avoided of $US50 254. The 4-year and lifetime incremental costs per QALY were
      $US18 409 and $US22 498, respectively. CONCLUSIONS: Despite increased cost due to
      taking a drug for prevention, dutasteride 0.5 mg/day may be cost effective in men
      at increased risk for PCa.

PMID- 21875162
TI  - Assessing quality of life among British older people using the ICEPOP CAPability
      (ICECAP-O) measure.
AB  - BACKGROUND: The Investigating Choice Experiments for the Preferences of Older
      People (ICEPOP) programme developed a capability-based measure of general quality
      of life (QOL): the ICEPOP CAPability (ICECAP-O) instrument. ICECAP-O was
      originally intended for use in the economic evaluation of health and social care
      interventions, but there is increasing interest in using it to quantify
      differences in QOL in cross-sectional data. OBJECTIVE: The objective of this
      study was to assess the construct validity of the overall ICECAP-O scores and
      quantify differences in QOL associated with various factors in a multivariable
      regression model among residents of a British city. METHODS: ICECAP-O was
      administered as part of a survey of 4304 citizens of a British city. QOL values
      in only those respondents aged >=65 years (n = 809) were compared across
      subgroups using univariable analyses and multivariable regression models.
      RESULTS: QOL values were associated with differences in responses to a variety of
      questions about respondents' socioeconomic status, locality, contact with others,
      participation, health and social support. Multivariable regression results showed
      that poor physical and psychological health were associated with 4-7% lower QOL.
      Living alone and infrequent socializing were each associated with an
      approximately 2.5% impairment in QOL. Feeling unsafe after dark was associated
      with an 8% impairment, whilst those without a faith experienced 5% lower QOL on
      average. Distribution of ICECAP-O values by electoral ward enabled the
      identification of areas of deprivation, although the associations were strong
      only for enjoyment and control. CONCLUSION: ICECAP-O provides policy makers with
      robust quantitative evidence of differences in QOL. It offers local government an
      opportunity to evaluate the effects of health and other interventions, and to
      make comparisons across sectors for which it is responsible. It also demonstrates
      good ability to compare impairments in QOL associated with sociodemographic,
      health and attitudinal variables.

PMID- 21875163
TI  - Early assessment of medical technologies to inform product development and market
      access: a review of methods and applications.
AB  - Worldwide, billions of dollars are invested in medical product development and
      there is an increasing pressure to maximize the revenues of these investments.
      That is, governments need to be informed about the benefits of spending public
      resources, companies need more information to manage their product development
      portfolios and even universities may need to direct their research programmes in
      order to maximize societal benefits. Assuming that all medical products need to
      be adopted by the heavily regulated healthcare market at one point in time, it is
      worthwhile to look at the logic behind healthcare decision making, specifically,
      decisions on the coverage of medical products and decisions on the use of these
      products under competing and uncertain conditions. With the growing tension
      between leveraging economic growth through R&D spending on the one hand and
      stricter control of healthcare budgets on the other, several attempts have been
      made to apply the health technology assessment (HTA) methodology to earlier
      stages of technology development and implementation. For instance, horizon
      scanning was introduced to systematically assess emerging technologies in order
      to inform health policy. Others have introduced iterative economic evaluation,
      e.g. economic evaluations in earlier stages of clinical research. However, most
      of these methods are primarily intended to support governments in making
      decisions regarding potentially expensive new medical products. They do not
      really inform biomedical product developers on the probability of return on
      investment, nor do they inform about the market needs and specific requirements
      of technologies in development. It is precisely this aspect that increasingly
      receives attention, i.e. is it possible to use HTA tools and methods to inform
      biomedical product development and to anticipate further development and market
      access. Several methods have been used in previous decades, but have never been
      compiled in a comprehensive review. The main objective of this article was to
      provide an overview of previous work and methods in the field of early HTA, and
      to put these approaches in perspective through a conceptual framework introduced
      in this paper. A particular goal of the review was to familiarize decision makers
      with available techniques that can be employed in early-stage decision making,
      and to identify opportunities for further methodological growth in this emerging
      field of HTA.

PMID- 21875165
TI  - Conceptual changes to the definition of borderline personality disorder proposed
      for DSM-5.
AB  - The Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 Personality and
      Personality Disorders Work Group proposed the elimination of diagnostic criterion
      sets in favor of a prototype matching system that defines personality disorders
      using narrative descriptions. Although some research supports this general
      approach, no empirical studies have yet examined the specific definitions
      proposed for DSM-5. Given the wide interest in borderline personality disorder
      (BPD), it is crucial to determine how this methodological shift might affect the
      content and conceptualization of the diagnosis. Eighty-two experts on BPD
      provided ratings of the DSM-IV-TR or DSM-5 version of BPD in terms of 37 traits
      proposed for DSM-5. Analyses revealed significant and meaningful differences
      among the two constructs, with the DSM-5 version evincing increased interpersonal
      dependency but a decreased emphasis on antagonism and disinhibition. A second
      study within a clinical sample demonstrated that both antagonism and
      disinhibition mediated the relationships between DSM-IV BPD and impairment,
      suggesting that the proposed changes might have important consequences for BPD's
      coverage, prevalence, and nomological network. More globally, our results
      illustrate that unanticipated shifts in diagnostic constructs can stem from
      seemingly minor revisions and suggest that research is needed to understand how
      these, or other changes, might affect our conceptualization, diagnosis, and
      treatment of BPD.

PMID- 21875167
TI  - Identifying component-processes of executive functioning that serve as risk
      factors for the alcohol-aggression relation.
AB  - The present investigation determined how different component-processes of
      executive functioning (EF) served as risk factors for intoxicated aggression.
      Participants were 512 (246 males and 266 females) healthy social drinkers between
      21 and 35 years of age. EF was measured using the Behavior Rating Inventory of
      Executive Function-Adult Version (BRIEF-A) that assesses nine EF components.
      After the consumption of either an alcohol or a placebo beverage, participants
      were tested on a modified version of the Taylor Aggression Paradigm in which mild
      electric shocks were received from, and administered to, a fictitious opponent.
      Aggressive behavior was operationalized as the shock intensities and durations
      administered to the opponent. Although a general BRIEF-A EF construct consisting
      of all nine components predicted intoxicated aggression, the best predictor
      involved one termed the Behavioral Regulation Index that comprises component
      processes such as inhibition, emotional control, flexible thinking, and self
      monitoring.

PMID- 21875166
TI  - Temporal discounting of rewards in patients with bipolar disorder and
      schizophrenia.
AB  - Patients with bipolar disorder (BD) and schizophrenia (SZ) often show decision
      making deficits in everyday circumstances. A failure to appropriately weigh
      immediate versus future consequences of choices may contribute to these deficits.
      We used the delay discounting task in individuals with BD or SZ to investigate
      their temporal decision making. Twenty-two individuals with BD, 21 individuals
      with SZ, and 30 healthy individuals completed the delay discounting task along
      with neuropsychological measures of working memory and cognitive function. Both
      BD and SZ groups discounted delayed rewards more steeply than did the healthy
      group even after controlling for current substance use, age, gender, and
      employment. Hierarchical multiple regression analyses showed that discounting
      rate was associated with both diagnostic group and working memory or intelligence
      scores. In each group, working memory or intelligence scores negatively
      correlated with discounting rate. The results suggest that (a) both BD and SZ
      groups value smaller, immediate rewards more than larger, delayed rewards
      compared with the healthy group and (b) working memory or intelligence is related
      to temporal decision making in individuals with BD or SZ as well as in healthy
      individuals.

PMID- 21875168
TI  - The role of illicit substance use in a conceptual model of intimate partner
      violence in men undergoing treatment for alcoholism.
AB  - Illicit substance use (ISU) predicts intimate partner violence (IPV) above and
      beyond alcohol use and other known IPV correlates. Stuart and colleagues (2008)
      provided evidence for a theoretical framework by which ISU contributes both
      directly and indirectly to IPV. We sought to replicate and extend their findings
      using data from 181 married or cohabiting heterosexual couples in which the male
      had recently begun a substance abuse treatment program and met criteria for
      alcohol dependence (97%) or abuse (3%). Using SEM, we found that (a) Stuart et
      al.'s model provided a good fit to the data; (b) men's cocaine use and women's
      sedative use emerged as particularly relevant to their respective perpetration of
      IPV; (c) a positive association between men's antisociality and physical
      aggression was mediated by increased stimulant use; and (d) the specific pattern
      of IPV predicted by women's sedative use differed across levels of aggression
      severity. These findings not only highlight the direct role of ISU in
      relationship aggression, but also support a larger theory-driven model comprising
      various proximal and distal precursors of IPV.

PMID- 21875169
TI  - Guidelines for psychological practice with lesbian, gay, and bisexual clients.

PMID- 21875170
TI  - Nonrational processes in ethical decision making.
AB  - Most current ethical decision-making models provide a logical and reasoned
      process for making ethical judgments, but these models are empirically unproven
      and rely upon assumptions of rational, conscious, and quasilegal reasoning. Such
      models predominate despite the fact that many nonrational factors influence
      ethical thought and behavior, including context, perceptions, relationships,
      emotions, and heuristics. For example, a large body of behavioral research has
      demonstrated the importance of automatic intuitive and affective processes in
      decision making and judgment. These processes profoundly affect human behavior
      and lead to systematic biases and departures from normative theories of
      rationality. Their influence represents an important but largely unrecognized
      component of ethical decision making. We selectively review this work; provide
      various illustrations; and make recommendations for scientists, trainers, and
      practitioners to aid them in integrating the understanding of nonrational
      processes with ethical decision making.

PMID- 21875171
TI  - Principles for quality undergraduate education in psychology.
AB  - The principles for undergraduate education in psychology presented here are
      designed for creating a world-class educational system that provides students
      with the workplace skills needed in this information age; a solid academic
      background that prepares them for advanced study in a wide range of fields; and
      the knowledge, skills, and abilities that will enhance their personal lives. A
      quality undergraduate education is designed to produce psychologically literate
      citizens who apply the principles of psychological science at work and at home.
      The American Psychological Association (APA) urges all stakeholders in
      undergraduate education in psychology to incorporate these principles in
      establishing goals and objectives that fit their specific institutional needs and
      missions.

PMID- 21875172
TI  - Predicting the performance and innovativeness of scientists and engineers.
AB  - A study of 644 scientists and engineers from 5 corporate research and development
      organizations investigated hypotheses generated from an interactionist framework
      of 4 individual characteristics as longitudinal predictors of performance and
      innovativeness. An innovative orientation predicted 1-year-later and 5-years
      later supervisory job performance ratings and 5-years-later counts of patents and
      publications. An internal locus of control predicted 5-years-later patents and
      publications, and self-esteem predicted performance ratings for both times and
      patents. Team-level nonroutine tasks moderated the individual-level relationships
      between an innovative orientation and performance ratings and patents such that
      the relationships were stronger in a nonroutine task environment. Implications
      for an interactionist framework of performance and innovativeness for knowledge
      workers are discussed.

PMID- 21875173
TI  - Bridging team faultlines by combining task role assignment and goal structure
      strategies.
AB  - This study tests whether the detrimental effects of strong diversity faultlines
      on team performance can be counteracted by combining 2 managerial strategies:
      task role crosscutting and superordinate goals. We conducted a 2 (crosscut vs.
      aligned roles) * 2 (superordinate vs. subgroup goals) experimental study. Seventy
      two 4-person teams with faultlines stemming from gender and educational major
      performed a complex decision-making task. The results show that teams with
      crosscut roles perform better when they are assigned a superordinate goal than a
      subgroup goal, whereas teams with aligned roles are not affected by goal
      manipulations. This effect is mediated by elaboration of task-relevant
      information. Implications for theory and management of team faultlines are
      discussed.

PMID- 21875174
TI  - Reactivation, interference, and reconsolidation: are recent and remote memories
      likewise susceptible?
AB  - The retrieval of a consolidated, apparently stable memory can return it to a
      labile state, necessitating another period of stabilization, termed
      reconsolidation. During reconsolidation, memories are susceptible to
      modifications, thus providing the opportunity to change unwanted memories. In a
      test of whether the possibility to alter retrieved memories depends on the age of
      the memories, participants learned a set of emotional and neutral pictures and
      recalled it 1, 7, or 28 days later. Immediately after retrieval, participants
      learned a second set of pictures. Memory retrieval per se enhanced 28-day-old
      memories but had no effect on 1-day- or 7-day-old memories. Learning new pictures
      interfered with 1-day-old and 28-day-old memories but not with 7-day-old
      memories. Evidence for reconsolidation effects was generally rather weak and at
      most present for 7-day-old memories. These findings show that retrieval and
      interference have opposite effects on memory that depend on the remoteness of the
      memories and raise the question under which conditions reconsolidation effects
      occur in human memory.

PMID- 21875175
TI  - Mindfulness is associated with fewer PTSD symptoms, depressive symptoms, physical
      symptoms, and alcohol problems in urban firefighters.
AB  - OBJECTIVE: This study investigated the association between mindfulness, other
      resilience resources, and several measures of health in 124 urban firefighters.
      METHOD: Participants completed health measures of posttraumatic stress disorder
      (PTSD) symptoms, depressive symptoms, physical symptoms, and alcohol problems and
      measures of resilience resources including mindfulness, optimism, personal
      mastery, and social support. The Mindful Awareness and Attention Scale (MAAS;
      Brown & Ryan, 2003) was used to assess mindfulness. Participants also completed
      measures of firefighter stress, number of calls, and years as a firefighter as
      control variables. Hierarchical multiple regressions were conducted with the
      health measures as the dependent variables with 3 levels of independent
      variables: (a) demographic characteristics, (b) firefighter variables, and (c)
      resilience resources. RESULTS: The results showed that mindfulness was associated
      with fewer PTSD symptoms, depressive symptoms, physical symptoms, and alcohol
      problems when controlling for the other study variables. Personal mastery and
      social support were also related to fewer depressive symptoms, firefighter stress
      was related to more PTSD symptoms and alcohol problems, and years as a
      firefighter were related to fewer alcohol problems. CONCLUSIONS: Mindfulness may
      be important to consider and include in models of stress, coping, and resilience
      in firefighters. Future studies should examine the prospective relationship
      between mindfulness and health in firefighters and others in high-stress
      occupations.

PMID- 21875176
TI  - Are word representations abstract or instance-based? Effects of spelling
      inconsistency in orthographic learning.
AB  - In Experiment 1, 62 10-year-old children studied printed pseudowords with
      semantic information. The items were later represented in a different format for
      reading, with half of the items spelled in the same way as before and half
      displayed in a new phonologically equivalent spelling. In a dictation test, the
      exposure to an alternative spelling substantially increased the number of errors
      that matched the alternative spelling, especially in good spellers. Orthographic
      learning predicted word identification when accuracy on orthographic choice for
      words was controlled. In Experiment 2, the effects on dictation responses of
      exposure to a misspelling versus the correct spelling, and the interactive effect
      of spelling ability, were confirmed relative to a no-exposure control in adults.
      The results support a single-lexicon view of reading and spelling and have
      implications for abstractionist and instance-based theories of orthographic
      representations.

PMID- 21875177
TI  - Acoustic variability and individual distinctiveness in the vocal repertoire of
      red-capped mangabeys (Cercocebus torquatus).
AB  - Acoustic variability and individual distinctiveness of vocal signals are expected
      to vary with both their communicative function and the need for individual
      recognition during social interactions. So far, few attempts have been made to
      comparatively study these features across the different call types within a
      species' vocal repertoire. We collected recordings of the six most common call
      types from 14 red-capped mangabeys (Cercocebus torquatus) to assess intra- and
      interindividual acoustic variability, using a range of temporal and frequency
      parameters. Acoustic variability was highest in contact and threat calls,
      intermediate in food calls, and lowest in loud and alarm calls. Individual
      distinctiveness was high in contact, threat, loud and alarm calls, and low in
      food calls. In sum, calls mediating intragroup social interactions were
      structurally most variable and individually most distinctive, highlighting the
      key role that social factors must have played in the evolution of the vocal
      repertoire in this species. We discuss these findings in light of existing
      hypotheses of acoustic variability in primate vocal behavior.

PMID- 21875178
TI  - Information theoretical approaches to chick-a-dee calls of Carolina chickadees
      (Poecile carolinensis).
AB  - One aim of this study was to apply information theoretical analyses to
      understanding the structural complexity of chick-a-dee calls of Carolina
      chickadees, Poecile carolinensis. A second aim of this study was to compare this
      structural complexity to that of the calls of black-capped chickadees, P.
      atricapillus, described in an earlier published report (Hailman, Ficken, &
      Ficken, 1985). Chick-a-dee calls were recorded from Carolina chickadees in a
      naturalistic observation study in eastern Tennessee. Calls were analyzed using
      approaches from information theory, including transition probability matrices,
      Zipf's rules, entropies, and information coding capacities of calls and notes of
      calls. As described for black-capped chickadees, calls of Carolina chickadees
      exhibited considerable structural complexity. Most results suggested that the
      call of Carolina chickadees is more structurally complex than that of black
      capped chickadees. These findings add support to the growing literature on the
      complexity of this call system in Paridae species. Furthermore, these results
      point to the feasibility of detailed cross-species comparative analyses that may
      allow strong testing of hypotheses regarding signal evolution.

PMID- 21875179
TI  - A qualitative inquiry of Latino immigrants' work experiences in the Midwest.
AB  - Latino immigrants are the largest source of immigrant workers in the United
      States. In this study, 11 first-generation Latino immigrants (8 men, 3 women)
      living in the Midwest were interviewed about their work experiences. Interview
      data were analyzed using consensual qualitative research methods (Hill, Thompson,
      & Williams, 1997). Five domains associated with the data included work for
      survival and power, work for social connections, work as self-determination, work
      barriers in the Midwest, and access to work in the Midwest. We identify ways in
      which vocational psychologists can intervene to work effectively with Latino
      newcomers seeking employment in the United States and to support their transition
      into new settlement communities. Suggestions for future research with immigrant
      workers are discussed.

PMID- 21875180
TI  - The Racial and Ethnic Microaggressions Scale (REMS): construction, reliability,
      and validity.
AB  - Racial microaggressions are subtle statements and behaviors that unconsciously
      communicate denigrating messages to people of color. In recent years, a
      theoretical taxonomy and subsequent qualitative studies have introduced the types
      of microaggressions that people of color experience. In the present study,
      college- and Internet-based samples of African Americans, Latina/os, Asian
      Americans, and multiracial participants (N = 661) were used to develop and
      validate the Racial and Ethnic Microaggression Scale (REMS). In Study 1, an
      exploratory principal-components analyses (n = 443) yielded a 6-factor model: (a)
      Assumptions of Inferiority, (b) Second-Class Citizen and Assumptions of
      Criminality, (c) Microinvalidations, (d) Exoticization/Assumptions of Similarity,
      (e) Environmental Microaggressions, and (f) Workplace and School
      Microaggressions, with a Cronbach's alpha of .912 for the overall model and
      subscales ranging from .783 to .873. In Study 2, a confirmatory factor analysis
      (n = 218) supported the 6-factor model with a Cronbach's alpha of .892. Further
      analyses indicate that the REMS is a valid measure of racial microaggressions, as
      evidenced by high correlations with existing measures of racism and participants'
      feedback. Future research directions and implications for practice are discussed.

PMID- 21875181
TI  - Racial/ethnic matching of clients and therapists in mental health services: a
      meta-analytic review of preferences, perceptions, and outcomes.
AB  - Across several decades the effects of matching clients with therapists of the
      same race/ethnicity have been explored using a variety of approaches. We
      conducted a meta-analysis of 3 variables frequently used in research on
      racial/ethnic matching: individuals' preferences for a therapist of their own
      race/ethnicity, clients' perceptions of therapists across racial/ethnic match,
      and therapeutic outcomes across racial/ethnic match. Across 52 studies of
      preferences, the average effect size (Cohen's d) was 0.63, indicating a
      moderately strong preference for a therapist of one's own race/ethnicity. Across
      81 studies of individuals' perceptions of therapists, the average effect size was
      0.32, indicating a tendency to perceive therapists of one's own race/ethnicity
      somewhat more positively than other therapists. Across 53 studies of client
      outcomes in mental health treatment, the average effect size was 0.09, indicating
      almost no benefit to treatment outcomes from racial/ethnic matching of clients
      with therapists. These 3 averaged effect sizes were characterized by substantial
      heterogeneity: The effects of racial/ethnic matching are highly variable. Studies
      involving African American participants demonstrated the highest effect sizes
      across all 3 types of evaluations: preferences, perceptions, and outcomes.

PMID- 21875182
TI  - Transgender individuals' workplace experiences: the applicability of sexual
      minority measures and models.
AB  - The present study explored whether 3 existing measures of workplace constructs
      germane to the experiences of sexual minority people could be modified to improve
      their applicability with transgender individuals. To this end, the Workplace
      Heterosexist Experiences Questionnaire (WHEQ; C. R. Waldo, 1999); the Lesbian,
      Gay, Bisexual, and Transgendered Climate Inventory (LGBTCI; B. J. Liddle, D. A.
      Luzzo, A. L. Hauenstein, & K. Schuck, 2004); and the Workplace Sexual Identity
      Management Measure (WSIMM; M. Z. Anderson, J. M. Croteau, Y. B. Chung, & T. M.
      DiStefano, 2001) were modified to explicitly address the experiences of
      transgender individuals. Data from a sample of 263 transgender individuals were
      used to evaluate the psychometric properties of the modified measures. Analyses
      of the structures of the modified measures (Transgender Forms [TF]) suggested an
      alternative 2-factor structure for the WHEQ-TF, but provided support for the
      previously observed unidimensional structure for the LGBTCI-TF, and a slightly
      modified 3-factor structure for the WSIMM-TF. Cronbach's alpha reliability
      coefficients for scale or subscale items across the 3 measures were acceptable.
      Criterion-related validity was evident in theoretically consistent patterns of
      correlations between scores on the 3 modified measures and scores on indicators
      of job satisfaction and outness. These data provide preliminary support for
      transgender-specific versions of measures of 3 key constructs in the sexual
      minority vocational behavior research.

PMID- 21875183
TI  - The social status of aggressive students across contexts: the role of classroom
      status hierarchy, academic achievement, and grade.
AB  - This study tested the effects of 5 classroom contextual features on the social
      status (perceived popularity and social preference) that peers accord to
      aggressive students in late elementary school, including classroom peer status
      hierarchy (whether within-classroom differences in popularity are large or
      small), classroom academic level, and grade level as the main predictors of
      interest as well as classroom aggression and ethnic composition as controls.
      Multilevel analyses were conducted on an ethnically diverse sample of 968 fourth-
      and fifth-graders from 46 classrooms in 9 schools. Associations between
      aggression and status varied greatly from one classroom to another. Aggressive
      students were more popular and better liked in classrooms with higher levels of
      peer status hierarchy. Aggressive students had higher social status in Grade 5
      than in Grade 4 and lower social preference in classrooms of higher academic
      level. Classroom aggression and ethnic composition did not moderate aggression
      status associations. Limitations and practical implications of these findings are
      discussed.

PMID- 21875184
TI  - Racial discrimination and racial socialization as predictors of African American
      adolescents' racial identity development using latent transition analysis.
AB  - The present study examined perceptions of racial discrimination and racial
      socialization on racial identity development among 566 African American
      adolescents over 3 years. Latent class analyses were used to estimate identity
      statuses (Diffuse, Foreclosed, Moratorium, and Achieved). The probabilities of
      transitioning from one stage to another were examined with latent transition
      analyses to determine the likelihood of youth progressing, regressing, or
      remaining constant. Racial socialization and perceptions of racial discrimination
      were examined as covariates to assess the association with changes in racial
      identity status. The results indicated that perceptions of racial discrimination
      were not linked to any changes in racial identity. Youth who reported higher
      levels of racial socialization were less likely to be in Diffuse or Foreclosed
      compared with the Achieved group.

PMID- 21875185
TI  - The role of familiarity in daily well-being: developmental and cultural
      variation.
AB  - The present study examined life stage and cultural differences in the degree to
      which familiarity of one's physical location and interaction partner is
      associated with daily well-being. Participants reported all the activities they
      engaged in and how they felt during these activities on a previous day using the
      Day Reconstruction Method (Kahneman, Krueger, Schkade, Schwarz, & Stone, 2004).
      Both Korean and American retirees were happier when in a familiar place than in
      an unfamiliar place, whereas the reverse was true for both Korean and American
      working adults. In addition, we found cultural differences in the role of
      familiarity of the interaction partner. Specifically, Koreans (both retirees and
      working adults) were substantially happier when they interacted with a familiar
      person than when they interacted with an unfamiliar person. In contrast,
      Americans (both retirees and working adults) were no happier with a familiar
      person than with an unfamiliar person.

PMID- 21875186
TI  - Trait anxiety and perceptual load as determinants of emotion processing in a fear
      conditioning paradigm.
AB  - The impact of trait anxiety and perceptual load on selective attention was
      examined in a fear conditioning paradigm. A fear-conditioned angry face (CS+), an
      unconditioned angry face (CS-), or an unconditioned face with a neutral or happy
      expression were used in distractor interference and attentional probe tasks. In
      Experiments 1 and 2, participants classified centrally presented letters under
      two conditions of perceptual load. When perceptual load was high, distractors had
      no effect on selective attention, even with aversive conditioning. However, when
      perceptual load was low, strong response interference effects for CS+ face
      distractors were found for low trait-anxious participants. Across both
      experiments, this enhanced distractor interference reversed to strong
      facilitation effects for those reporting high trait anxiety. Thus, high trait
      anxious participants were faster, rather than slower, when ignoring CS+
      distractors. Using an attentional probe task in Experiment 3, it was found that
      fear conditioning resulted in strong attentional avoidance in a high trait
      anxious group, which contrasted with enhanced vigilance in a low trait-anxious
      group. These results demonstrate that the impact of fear conditioning on
      attention is modulated by individual variation in trait anxiety when perceptual
      load is low. Fear conditioning elicits an avoidance of threat-relevant stimuli in
      high trait-anxious participants.

PMID- 21875187
TI  - The orienting of spatial attention to backward masked fearful faces is associated
      with variation in the serotonin transporter gene.
AB  - Threat signals facilitate spatial attention, even when awareness of these signals
      has been restricted through the use of backward masking. However,
      unrestricted/unmasked threat cues tend to delay the disengagement of attention,
      whereas restricted/masked threat facilitates orienting, suggesting different
      underlying mechanisms. Within the general population, the serotonin transporter
      gene polymorphism (5HTTLPR) is associated with one's allocation of attention to
      unmasked threat signals. However, it is unclear to what extent the 5HTTLPR gene
      may be involved in nonconscious biases to masked threat, and whether or not such
      biases are driven by facilitated orienting or delayed disengagement. Participants
      were genotyped and performed a dot-probe task with backward masked fearful and
      neutral faces. Results indicate that short-allele carriers of the 5HTTLPR gene
      nonconsciously orient spatial attention to masked fearful faces. On the other
      hand, homozygous long-allele individuals tended to direct attention away from
      masked fearful faces. All participants' performance was at chance in a posttask
      assessment of awareness for the masked faces. The results add to current
      literature on the 5HTTLPR and attention biases, and suggest that threat signals
      facilitate the orienting of attention in short-allele carriers of the 5HTTLPR
      gene even under restricted processing conditions.

PMID- 21875188
TI  - The sound of the crowd: auditory information modulates the perceived emotion of a
      crowd based on bodily expressions.
AB  - Although both auditory and visual information can influence the perceived emotion
      of an individual, how these modalities contribute to the perceived emotion of a
      crowd of characters was hitherto unknown. Here, we manipulated the ambiguity of
      the emotion of either a visual or auditory crowd of characters by varying the
      proportions of characters expressing one of two emotional states. Using an
      intersensory bias paradigm, unambiguous emotional information from an unattended
      modality was presented while participants determined the emotion of a crowd in an
      attended, but different, modality. We found that emotional information in an
      unattended modality can disambiguate the perceived emotion of a crowd. Moreover,
      the size of the crowd had little effect on these crossmodal influences. The role
      of audiovisual information appears to be similar in perceiving emotion from
      individuals or crowds. Our findings provide novel insights into the role of
      multisensory influences on the perception of social information from crowds of
      individuals.

PMID- 21875189
TI  - Approach motivation as incentive salience: perceptual sources of evidence in
      relation to positive word primes.
AB  - Four experiments (total N = 391) examined predictions derived from a biologically
      based incentive salience theory of approach motivation. In all experiments,
      judgments indicative of enhanced perceptual salience were exaggerated in the
      context of positive, relative to neutral or negative, stimuli. In Experiments 1
      and 2, positive words were judged to be of a larger size (Experiment 1) and led
      individuals to judge subsequently presented neutral objects as larger in size
      (Experiment 2). In Experiment 3, similar effects were observed in a mock
      subliminal presentation paradigm. In Experiment 4, positive word primes were
      perceived to have been presented for a longer duration of time, again relative to
      both neutral and negative word primes. Results are discussed in relation to
      theories of approach motivation, affective priming, and the motivation-perception
      interface.

PMID- 21875190
TI  - Action compatibility effects are hedonically marked and have incidental
      consequences on affective judgment.
AB  - Recent results from Cannon, Hayes, and Tipper (2010) have established that the
      Action Compatibility Effect (ACE) is hedonically marked and elicits a genuine
      positive reaction. In this work, we aim to show that the hedonic marking of the
      ACE has incidental consequences on affective judgment. For this, we used the
      affective priming paradigm principle (for a review, see Musch & Klauer, 2003):
      participants have to respond, as quickly as they can, regarding the pleasantness
      or unpleasantness character of a target word. In the priming phase, we do not
      present an affective stimulus; however, we present two different graspable
      objects, one after the other. The handles of the graspable objects are shown
      either both on the same side (i.e., perceptual action compatibility) or not
      (i.e., perceptual action incompatibility). In addition, the orientation of the
      handles of the objects are either compatible (i.e., action compatibility) or not
      (i.e., action compatibility) with the response hand used for the word evaluation.
      Consistent with our hypothesis, participants responded faster to positive words
      after perceptual action compatibility and action compatibility (thus
      demonstrating the ACE) than after incompatibility conditions.

PMID- 21875191
TI  - Two versions of life: emotionally negative and positive life events have
      different roles in the organization of life story and identity.
AB  - Over 2,000 adults in their sixties completed the Centrality of Event Scale (CES)
      for the traumatic or negative event that now troubled them the most and for their
      most positive life event, as well as measures of current PTSD symptoms,
      depression, well-being, and personality. Consistent with the notion of a
      positivity bias in old age, the positive events were judged to be markedly more
      central to life story and identity than were the negative events. The centrality
      of positive events was unrelated to measures of PTSD symptoms and emotional
      distress, whereas the centrality of the negative event showed clear positive
      correlations with these measures. The centrality of the positive events increased
      with increasing time since the events, whereas the centrality of the negative
      events decreased. The life distribution of the positive events showed a marked
      peak in young adulthood whereas the life distribution for the negative events
      peaked at the participants' present age. The positive events were mostly events
      from the cultural life script-that is, culturally shared representations of the
      timing of major transitional events. Overall, our findings show that positive and
      negative autobiographical events relate markedly differently to life story and
      identity. Positive events become central to life story and identity primarily
      through their correspondence with cultural norms. Negative events become central
      through mechanisms associated with emotional distress.

PMID- 21875192
TI  - Development of the Brief Romantic Relationship Interaction Coding Scheme
      (BRRICS).
AB  - Although observational studies of romantic relationships are common, many
      existing coding schemes require considerable amounts of time and resources to
      implement. The current study presents a new coding scheme, the Brief Romantic
      Relationship Interaction Coding Scheme (BRRICS), designed to assess various
      aspects of romantic relationship both quickly and efficiently. The BRRICS
      consists of four individual coding dimensions assessing positive and negative
      affect in each member of the dyad, as well as four codes assessing specific
      components of the dyadic interaction (i.e., positive reciprocity, demand-withdraw
      pattern, negative reciprocity, and overall satisfaction). Concurrent associations
      with measures of marital adjustment and conflict were evaluated in a sample of
      118 married couples participating in the Michigan State University Twin Registry.
      Couples were asked to discuss common conflicts in their marriage while being
      videotaped. Undergraduate coders used the BRRICS to rate these interactions. The
      BRRICS scales were correlated in expected directions with self-reports of marital
      adjustment, as well as children's perception of the severity and frequency of
      marital conflict. Based on these results, the BRRICS may be an efficient tool for
      researchers with large samples of observational data who are interested in coding
      global aspects of the relationship but do not have the resources to use labor
      intensive schemes.

PMID- 21875193
TI  - Mechanisms underlying the influence of disruptive child behavior on interparental
      communication.
AB  - Prospective and experimental manipulations of child behavior have demonstrated
      that disruptive child behavior causes interparental discord. However, research
      has yet to test for mechanisms underlying this causal pathway. There is reason to
      suspect parent affect and parenting behavior explain child effects on
      interparental relations. To investigate this hypothesis, parent couples of 9- to
      12-year-old boys and girls with attention-deficit/hyperactivity disorder (ADHD; n
      = 51) and without ADHD (n = 39) were randomly assigned to interact with a
      confederate child exhibiting "disruptive" or "typical" behavior. Parents rated
      their own affect, as well as the quality of their partner's parenting and
      communication, immediately following the interaction. Observers also coded the
      quality of parenting and communication behaviors parents exhibited during the
      interaction. Parents who interacted with disruptive confederates reported lower
      positive affect and higher negative affect than those who interacted with typical
      confederates. Parents were also noted by their partners and observers to parent
      disruptive confederates more negatively than typical confederates. Multilevel
      mediation models with observational coding and partner ratings both found that
      negative parenting explained the causal pathway between disruptive child behavior
      and negative communication. Exploratory analyses revealed that the strength of
      this pathway did not differ between parents of children with and without ADHD.
      Parent affect was not found to explain child effects on interparental
      communication. Though methodological issues limit the generalizability of these
      findings, results indicate that negative parenting may be one mechanism through
      which disruptive children cause interparental discord.

PMID- 21875194
TI  - Positive-engagement behaviors in observed family interactions: a social relations
      perspective.
AB  - The present study investigates the nature of positive engagement (an
      interpersonal style characterized by attentiveness, warmth, cooperation, and
      clear communication) in family interactions involving at least one adolescent.
      Approximately 400 families (mothers, fathers, and two siblings) were videotaped
      during brief conflict-resolution discussions that occurred on a yearly basis for
      3 years. Coders rated the degree to which each family member was positively
      engaged with every other family member during the interactions. The social
      relations model was used to partition variation in positive-engagement behavior
      into family-level, individual-level, and dyad-level effects. Results demonstrated
      the importance of family norms and individual factors in determining the
      expression of positive-engagement behaviors in dyadic family relationships.
      Moreover, longitudinal analyses indicated that these effects are stable over a 3
      year period. Finally, results highlighted the relative distinctiveness of the
      marital and sibling relationships, as well as the existence of reciprocity within
      these dyads.

PMID- 21875195
TI  - Premature termination in couple therapy with veterans: definitions and prediction
      of long-term outcomes.
AB  - Premature termination (PT) has been identified as widespread in individual,
      family, and couple therapy. Unfortunately, research on PT utilizes numerous
      definitions of PT without providing guidance on which definition may be most
      clinically useful. The current study investigated seven definitions of PT (three
      based on therapist ratings and four based on quantitative measures) utilizing a
      sample of 177 couples seeking treatment at two Department of Veterans Affairs
      medical centers. Results indicated that PT occurred in 50-80% of couples;
      however, agreement between the definitions of PT was generally only in the slight
      to fair range, making it difficult to determine whether a particular couple was
      ready to terminate treatment. Additionally, many commonly used definitions of PT
      were unrelated to level or maintenance of relationship functioning following
      treatment. In contrast, two definitions of PT (ending treatment in the distressed
      range and therapist-rated likelihood of future unhappiness) significantly
      predicted larger decreases in relationship satisfaction during the 18 months
      following therapy, as well as lower levels of satisfaction and relationship
      stability 18 months after termination. Additionally, long-term relationship
      functioning was especially poor when both these definitions of PT were met,
      suggesting that both qualitative and quantitative definitions should inform
      decisions about termination in couple therapy.

PMID- 21875196
TI  - Enduring vulnerabilities, relationship attributions, and couple conflict: an
      integrative model of the occurrence and frequency of intimate partner violence.
AB  - We tested an integrative model of individual and dyadic variables contributing to
      intimate partner violence (IPV) perpetration. Based on the vulnerability-stress
      adaptation (VSA) model, we hypothesized that three "enduring vulnerabilities"
      (i.e., antisocial behavior, hostility, and depressive symptoms) would be
      associated with a "maladaptive process" (i.e., negative relationship
      attributions) that would lead to difficulties in couple conflict resolution, thus
      leading to IPV. Among a community sample of 167 heterosexual couples who were
      expecting their first child, we used an actor-partner interdependence model to
      account for the dyadic nature of conflict and IPV, as well as a hurdle count
      model to improve upon prior methods for modeling IPV data. Study results provided
      general support for the integrative model, demonstrating the importance of
      considering couple conflict in the prediction of IPV and showing the relative
      importance of multiple predictor variables. Gender symmetry was observed for the
      prediction of IPV occurrence, with gender differences emerging in the prediction
      of IPV frequency. Relatively speaking, the prediction of IPV frequency appeared
      to be a function of enduring vulnerabilities among men, but a function of couple
      conflict among women. Results also revealed important cross-gender effects in the
      prediction of IPV, reflecting the inherently dyadic nature of IPV, particularly
      in the case of "common couple violence." Future research using longitudinal
      designs is necessary to verify the conclusions suggested by the current results.

PMID- 21875197
TI  - Sanctification of sexuality: implications for newlyweds' marital and sexual
      quality.
AB  - Research on the intersection of sexuality, religion, and spirituality has
      primarily examined whether global levels of religiousness (e.g., service
      attendance) deter premarital and extramarital sexual activity. Virtually no
      empirical work has addressed whether specific spiritual beliefs about sexuality
      enhance marital sexuality. Using a community sample of 83 individuals married
      between 4 and 18 months, we found that greater perceptions of sexuality as
      sanctified predicted greater marital satisfaction, sexual satisfaction, sexual
      intimacy, and spiritual intimacy beyond global religiousness and demographics.
      The findings open a new line of research on religion and family life, and extend
      theories on the possible benefits of the sanctification of intimate
      relationships.

PMID- 21875198
TI  - Maternal depression and the heart of parenting: respiratory sinus arrhythmia and
      affective dynamics during parent-adolescent interactions.
AB  - Maternal depression is associated with problematic parenting and the development
      of emotional and behavior problems in children and adolescents. While emotional
      regulatory abilities are likely to influence emotional exchanges between parents
      and teens, surprisingly little is known about the role of emotion regulation
      during parent-child interactions, particularly in high-risk families. Respiratory
      sinus arrhythmia (RSA) has been widely linked to emotion regulatory abilities in
      recent research, and the current study investigated RSA and maternal depression
      in relation to dyadic flexibility, as well as mutuality of negative and positive
      affect displayed during three discussion tasks between 59 mother-adolescent pairs
      (age 11-17 years). Dyadic flexibility was predicted by the interaction of
      maternal depression, maternal RSA, and teen RSA, with higher maternal RSA
      predicting greater dyadic flexibility, particularly in highest risk dyads (i.e.,
      elevated maternal depression and lower teen RSA). Teen RSA interacted with
      maternal depression to predict mutual negative affect, serving as a protective
      factor. Finally, maternal and teen RSA interacted to predict mutual positive
      affect, with maternal RSA buffering against low teen RSA to predict higher mutual
      positive affect. Results support the role of RSA in affectively laden
      interactions between parents and adolescents, particularly in the face of
      maternal depression.

PMID- 21875199
TI  - Parents matter in HIV-risk among probation youth.
AB  - We investigated the relationship between parenting practices (i.e., parental
      monitoring, parent permissiveness, and parent-teen communication), and probation
      youth's HIV-related sexual risk behavior (i.e., ever having sex, condom use,
      alcohol and marijuana use before sex). Participants were 61 male and female
      juvenile offenders, ages 13-17, on probation and awaiting sentencing. Results
      indicated different relationships between parenting and HIV-related sexual risk
      behavior for probation boys and girls. Parental monitoring, parenting
      permissiveness, and parent-teen communication were collectively related to
      whether girls' ever had sex and with boys' use of alcohol and marijuana use
      before last sex. Findings underscore the important role of parenting on probation
      teens' HIV risk behaviors.

PMID- 21875200
TI  - Parenting at risk: new perspectives, new approaches.
AB  - In this lead paper for this special section, we advance the perspective that new
      insights into parenting at risk can be gained by focusing on the dynamic
      emotional processes that occur during parent-child exchanges, with special
      emphasis on parental emotions as experienced and their regulation of emotion and
      underlying cognitions, as well as the role of developmentally rooted cognitions
      in shaping these associations. We discuss the very few but germinal studies that
      embody this perspective and introduce work in this section that examines emotion
      dynamics during parenting in real time. We believe this perspective will move us
      beyond static conceptualizations of parenting at risk, broadens our understanding
      of parenting as a process, and accelerates our ability to identify the essential
      targets of intervention when parenting is at risk.

PMID- 21875201
TI  - Risk and resilience in military families experiencing deployment: the role of the
      family attachment network.
AB  - Deployment separation constitutes a significant stressor for U.S. military men
      and women and their families. Many military personnel return home struggling with
      physical and/or psychological injuries that challenge their ability to
      reintegrate and contribute to marital problems, family dysfunction, and emotional
      or behavioral disturbance in spouses and children. Yet research examining the
      psychological health and functioning of military families is scarce and rarely
      driven by developmental theory. The primary purpose of this theoretical paper is
      to describe a family attachment network model of military families during
      deployment and reintegration that is grounded in attachment theory and family
      systems theory. This integrative perspective provides a solid empirical
      foundation and a comprehensive account of individual and family risk and
      resilience during military-related separations and reunions. The proposed family
      attachment network model will inform future research and intervention efforts
      with service members and their families.

PMID- 21875202
TI  - The association between parental warmth and control in thirteen cultural groups.
AB  - The goal of the current study was to investigate potential cross-cultural
      differences in the covariation between two of the major dimensions of parenting
      behavior: control and warmth. Participants included 1,421 (51% female) 7- to 10
      year-old (M = 8.29, SD = .67 years) children and their mothers and fathers
      representing 13 cultural groups in nine countries in Africa, Asia, Europe, the
      Middle East, and North and South America. Children and parents completed
      questionnaires and interviews regarding mother and father control and warmth.
      Greater warmth was associated with more control, but this association varied
      widely between cultural groups.

PMID- 21875203
TI  - "Making the child understand:" socialization of emotion in urban India.
AB  - Using a combination of quantitative and qualitative methods, this study examined
      mothers' socialization of child emotion in suburban middle-class families in
      Gujarat, India. In particular, a community sample of 602 children, 6 to 8 years,
      was screened for emotional/behavioral problems using a parent-report measure
      standardized with this population. Based on the screening, four groups of
      children were formed: those with internalizing problems (n = 31), externalizing
      problems (n = 32), and somatic complaints (n = 25), and an asymptomatic control
      group (n = 32). Mothers of children across groups completed a previously pilot
      tested, forced-choice, self-report questionnaire of their emotions and behaviors
      in response to their children's anger, sadness, and physical pain, and an
      individual open-ended interview further exploring their socialization behaviors,
      immediate goals, and expectations from their children. Quantitative data revealed
      that mothers of children in internalizing, externalizing, and somatic complaints
      groups reported more negative emotions (anger, disappointment, embarrassment,
      restlessness) and punitive/ minimizing behaviors than the control group, with the
      somatic-complaints group also reporting less sympathy and emotion-/ problem
      focused behaviors than the control group. Qualitative data provided a culturally
      grounded overarching framework to understand emotion socialization in this
      sample, and suggested variation across groups with respect to the type of
      mothers' behaviors, along with expectations for appropriate behavior.

PMID- 21875204
TI  - Valued life activities and readiness to quit smoking among mobility-impaired
      smokers.
AB  - OBJECTIVE: People with physical disabilities smoke at a higher rate than their
      nondisabled peers, with rates as high as 28-40% among nonelderly adults. One
      possible explanation for these findings is that restriction of valued life
      activities (social, professional, pleasurable or otherwise meaningful) due to
      mobility impairment interferes with smoking cessation. METHODS: Forty-seven
      smokers (48.9% female; Mage = 48.91) with chronic mobility impairments (i.e.,
      regularly use equipment to ambulate) were interviewed over the telephone. We
      assessed demographics, self-efficacy to quit smoking, stage of change, current
      engagement in valued activities, current restriction of valued activities due to
      physical limitations, and efforts to replace restricted valued activities in a
      cross sectional design. RESULTS: Bivariate results indicate that 74% of those in
      the preparation stage had satisfactory replacements for their most valued
      restricted activity, whereas only 27% in the contemplation stage and 17% in the
      precontemplation stage had such satisfactory replacements. Multinomial ordinal
      regression analyses revealed that (a) having satisfactory replacements for
      activities restricted due to physical disability was significantly associated
      with higher stage of change and (b) more current valued activities and, to a
      lesser extent, fewer restricted activities were significantly associated with
      higher levels of self-efficacy to quit smoking. CONCLUSIONS: These results
      support the need for the development of treatments for smoking cessation that aim
      to increase engagement in valued activities, such as behavioral activation.

PMID- 21875205
TI  - Can self-prediction overcome barriers to Hepatitis B vaccination? A randomized
      controlled trial.
AB  - OBJECTIVE: Hepatitis B virus (HBV) infection remains a serious public health
      problem, due in part to low vaccination rates among high-risk adults, many of
      whom decline vaccination because of barriers such as perceived inconvenience or
      discomfort. This study evaluates the efficacy of a self-prediction intervention
      to increase HBV vaccination rates among high-risk adults. METHOD: Randomized
      controlled trial of 1,175 adults recruited from three sexually transmitted
      disease clinics in the United States over 28 months. Participants completed an
      audio-computer-assisted self-interview, which presented information about HBV
      infection and vaccination, and measured relevant beliefs, behaviors, and
      demographics. Half of participants were assigned randomly to a "self-prediction"
      intervention, asking them to predict their future acceptance of HBV vaccination.
      The main outcome measure was subsequent vaccination behavior. Other measures
      included perceived barriers to HBV vaccination, measured prior to the
      intervention. RESULTS: There was a significant interaction between the
      intervention and vaccination barriers, indicating the effect of the intervention
      differed depending on perceived vaccination barriers. Among high-barriers
      patients, the intervention significantly increased vaccination acceptance. Among
      low-barriers patients, the intervention did not influence vaccination acceptance.
      CONCLUSIONS: The self-prediction intervention significantly increased vaccination
      acceptance among "high-barriers" patients, who typically have very low
      vaccination rates. This brief intervention could be a useful tool in increasing
      vaccine uptake among high-barriers patients.

PMID- 21875207
TI  - Translating science to practice: Clinical Grand Rounds Series in Health
      Psychology.
AB  - In this issue of Health Psychology we launch an important new series focused on
      the implementation of evidence-based assessments and interventions in clinical
      settings. The series-Translating Science into Practice: Clinical Grand Rounds-is
      consistent with the journal's emphasis on the practical significance of papers in
      Health Psychology and congruent with national and international trends in
      evidence-based care and translational science across all health disciplines.

PMID- 21875208
TI  - Injury severity and outcome: a meta-analysis of prospective studies on TBI
      outcome.
AB  - OBJECTIVE: The recent movement to apply evidenced-based approaches to medical and
      rehabilitation care has increased the importance of approximating outcomes as
      early in the recovery process as possible. The relationship between injury
      severity and outcome following traumatic brain injury (TBI), however, has
      remained unclear due to the variety of predictor and criterion variables used
      throughout the literature. METHOD: A meta-analysis of eligible prospective
      studies that assessed the bivariate association between injury severity and
      outcome at 1-year postinjury was conducted. RESULTS: Twenty-six studies met the
      inclusion criteria (total N = 21,050 patients). Injury severity was a significant
      predictor of outcome at 1-year postinjury (r = .257). Homogeneity testing by
      means of the Q test, Q(n), indicated that injury severity measurement, Q(68) =
      1140.76, p < .00001, outcome measurement, Q(42) = 516.63, p < .00001, and outcome
      measurement construct, Q(4) = 14.65, p = .006, were significant moderators of the
      injury severity/outcome link. Further, the magnitude of the effect between injury
      severity and outcome resulted from a significant interaction between the measure
      of injury severity and the outcome construct. CONCLUSIONS: Overall, measures of
      injury severity were most significantly associated with measures of global
      outcome and most poorly associated with measures of satisfaction with life.
      Additionally, a significant interaction was found between the measure of injury
      severity and the outcome construct indicating that different measures of injury
      severity more precisely predict one outcome construct over another.
      Methodological concerns were discussed and recommendations for creating a more
      parsimonious and integrated literature base were made.

PMID- 21875206
TI  - The different roles of perceived stress in the association between older adults'
      physical activity and physical health.
AB  - OBJECTIVE: This 4-year longitudinal study examined the different roles of
      perceived stress in the association between older adults' physical activities and
      physical health. We hypothesized that physical activities would exert beneficial
      effects on physical health by preventing chronically high levels of perceived
      stress. METHODS: We assessed baseline levels of physical activities and repeated
      measures of perceived stress and physical symptoms in 3 waves of data from a
      sample of 157 older adults. RESULTS: Among participants with high (but not low)
      baseline levels of perceived stress, physical activity predicted a 2-year
      reduction of perceived stress and a 4-year prevention of physical health
      symptoms. Moreover, the interaction effect on 4-year changes in physical symptoms
      was mediated by 2-year changes in perceived stress. CONCLUSIONS: Physical health
      benefits of physical activity are particularly pronounced among older adults who
      perceive high levels of stress, and this effect is mediated by a prevention of
      chronically high perceptions of stress.

PMID- 21875209
TI  - The effects of expressive writing following first myocardial infarction: a
      randomized controlled trial.
AB  - OBJECTIVE: To assess the effects of expressive writing on health care
      utilization, clinical variables and subjective quality of life following first
      myocardial infarction (MI). METHODS: One-hundred and seventy-nine first MI
      patients were randomized to Intervention (N = 88) or Control (N = 91) groups. The
      intervention group wrote about their thoughts and feelings in relation to having
      had an MI. Controls wrote in a neutral way about daily activities. The main
      outcome measures were health care utilization, physical status and subjective
      quality of life (QOL), assessed after one, two, and five months. RESULTS: One
      hundred and fifty-six (87%) completed the study. Five months post-intervention,
      the intervention group had significantly fewer recorded medical appointments
      compared to controls. The number of prescribed medicines decreased over time
      within the intervention group but increased within the control group. The
      intervention group attended significantly more rehabilitation sessions, reported
      fewer cardiac related symptoms and had lower diastolic blood pressure five months
      post-intervention. There was no significant group by time interaction on reported
      physical health. The group by time interaction on reported mental health
      approached significance, those in the intervention group reporting greater
      improvement. CONCLUSION: Expressive writing may be a beneficial strategy which
      could be incorporated into rehabilitation interventions to help individuals
      adjust after first MI.

PMID- 21875210
TI  - Free to be you and me: a climate of authenticity alleviates burnout from
      emotional labor.
AB  - Given the emotional nature of health care, patients and their families may
      express anger and mistreat their health care providers; in addition, those
      providers are expected to manage their own emotions when providing care--two
      interpersonal stressors that are linked to job burnout. Integrating conservation
      of resources (Hobfoll, 2002) and ego depletion (Muraven & Baumeister, 2000)
      theories, we propose that this creates a resource loss spiral that can be slowed
      by the presence of a "climate of authenticity" among one's coworkers. We describe
      this climate and how it differs from other work climates. We then propose that a
      work unit with a climate of authenticity should provide a self-regulatory break
      from emotional labor with patients, thus replenishing resources and buffering
      against strain from emotional labor. We tested this multilevel prediction by
      surveying 359 health care providers nested within 48 work units at a large,
      metropolitan hospital. We find that medical workers experiencing more
      mistreatment by patients are more likely to be managing emotions with patients,
      and this response further contributes to the employees' job-related burnout. As
      predicted, managing emotions with patients was unrelated to burnout for workers
      in a unit with a climate of authenticity.

PMID- 21875211
TI  - Promoting safety voice with safety-specific transformational leadership: the
      mediating role of two dimensions of trust.
AB  - Although safety-specific transformational leadership is known to encourage
      employee safety voice behaviors, less is known about what makes this style of
      leadership effective. We tested a model that links safety-specific
      transformational leadership to safety voice through various dimensions of trust.
      Data from 150 supervisor-employee dyads from the United Kingdom oil industry
      supported our predictions that the effects of safety-specific transformational
      leadership are sequentially mediated by affect-based trust beliefs and disclosure
      trust intentions. Moreover, we found that reliance trust intentions moderated the
      effect of disclosure: employees' disclosure intentions mediated the effects of
      affect-based trust on safety voice behaviors only when employees' intention to
      rely on their leader was moderate to high. These findings suggest that leaders
      seeking to encourage safety voice behaviors should go beyond "good reason"
      arguments and develop affective bonds with their employees.

PMID- 21875212
TI  - Attendance dynamics at work: the antecedents and correlates of presenteeism,
      absenteeism, and productivity loss.
AB  - Presenteeism is attending work when ill. This study examined the antecedents and
      correlates of presenteeism, absenteeism, and productivity loss attributed to
      presenteeism. Predictors included work context, personal characteristics, and
      work experiences. Business school graduates employed in a variety of work
      positions (N = 444) completed a Web-based survey. Presenteeism was positively
      associated with task significance, task interdependence, ease of replacement, and
      work to family conflict and negatively associated with neuroticism, equity, job
      security, internal health locus of control, and the perceived legitimacy of
      absence. Absenteeism was positively related to task significance, perceived
      absence legitimacy, and family to work conflict and negatively related to task
      interdependence and work to family conflict. Those high on neuroticism, the
      unconscientious, the job-insecure, those who viewed absence as more legitimate,
      and those experiencing work-family conflict reported more productivity loss.
      Overall, the results reveal the value of a behavioral approach to presenteeism
      over and above a strict medical model. (PsycINFO Database Record (c) 2011 APA,
      all rights reserved).

PMID- 21875214
TI  - Internalization of age stereotypes into the self-concept via future self-views: a
      general model and domain-specific differences.
AB  - We investigated a pathway through which age stereotypes (AS) become internalized
      into the self. Domain-specific AS, as well as future self-views (FS) and current
      self-views (CS), were assessed in a sample of middle-aged and older adults. AS
      were positively related to CS and this effect was mediated via FS. These
      relations were stronger for older persons, indicating that the internalization
      process depends on a self-categorization as being old. A comparison of life
      domains revealed that an age-dependent internalization of AS emerged mainly for
      those domains in which age-related changes are expected to occur during later
      phases of life.

PMID- 21875213
TI  - Motivational reserve: motivation-related occupational abilities and risk of mild
      cognitive impairment and Alzheimer disease.
AB  - Midlife motivational abilities, that is, skills to initiate and persevere in the
      implementation of goals, have been related to mental and physical health, but
      their association with risk of mild cognitive impairment (MCI) and Alzheimer's
      disease (AD) has not yet been directly investigated. This relation was examined
      with data from the German Study on Ageing, Cognition, and Dementia in Primary
      Care Patients (AgeCoDe). A total of 3,327 nondemented participants (50.3% of a
      randomly selected sample) aged 75-89 years were recruited in primary care and
      followed up twice (after 1.5 and 3 years). Motivation-related occupational
      abilities were estimated on the basis of the main occupation (assessed at follow
      up II) using the Occupational Information Network (O* NET) database, which
      provides detailed information on worker characteristics and abilities. Cox
      proportional hazards models were used to evaluate the relative risk of developing
      MCI and AD in relation to motivation-related occupational abilities, adjusting
      for various covariates. Over the 3 years of follow-up, 15.2% participants
      developed MCI and 3.0% developed AD. In a fully adjusted model, motivation
      related occupational abilities were found to be associated with a reduced risk of
      MCI (HR: 0.77; 95% CI: 0.64-0.92). Motivation-related occupational abilities were
      associated with reduced risk of AD in ApoE epsilon4 carriers (HR: 0.48; CI: 0.25
      0.91), but not in noncarriers (HR: 0.99; CI: 0.65-1.53). These results suggest
      that midlife motivational abilities are associated with reduced risk of MCI in
      general and with reduced risk of AD in ApoE epsilon4 carriers. Revealing the
      mechanisms underlying this association may inform novel prevention strategies for
      decelerating cognitive decline in old age.

PMID- 21875215
TI  - Normal aging and the dissociable prototype learning systems.
AB  - Dissociable prototype learning systems have been demonstrated behaviorally and
      with neuroimaging in younger adults as well as with patient populations. In A/not
      A (AN) prototype learning, participants are shown members of category A during
      training, and during test are asked to decide whether novel items are in category
      A or are not in category A. Research suggests that AN learning is mediated by a
      perceptual learning system. In A/B (AB) prototype learning, participants are
      shown members of category A and B during training, and during test are asked to
      decide whether novel items are in category A or category B. In contrast to AN,
      research suggests that AB learning is mediated by a declarative memory system.
      The current study examined the effects of normal aging on AN and AB prototype
      learning. We observed an age-related deficit in AB learning, but an age-related
      advantage in AN learning. Computational modeling supports one possible
      interpretation based on narrower selective attentional focus in older adults in
      the AB task and broader selective attention in the AN task. Neuropsychological
      testing in older participants suggested that executive functioning and
      attentional control were associated with better performance in both tasks.
      However, nonverbal memory was associated with better AN performance, while visual
      attention was associated with worse AB performance. The results support an
      interactive memory systems approach and suggest that age-related declines in one
      memory system can lead to deficits in some tasks, but to enhanced performance in
      others.

PMID- 21875216
TI  - Multiple trajectories of depressive symptoms in middle and late life:
      racial/ethnic variations.
AB  - This research aims to identify distinct courses of depressive symptoms among
      middle-aged and older Americans and to ascertain how these courses vary by
      race/ethnicity. Data came from the 1995-2006 Health and Retirement Study which
      involved a national sample of 17,196 Americans over 50 years of age with up to
      six repeated observations. Depressive symptoms were measured by an abbreviated
      version of the Center for Epidemiologic Studies Depression scale. Semiparametric
      group based mixture models (Proc Traj) were used for data analysis. Six major
      trajectories were identified: (a) minimal depressive symptoms (15.9%), (b) low
      depressive symptoms (36.3%), (c) moderate and stable depressive symptoms (29.2%),
      (d) high but decreasing depressive symptoms (6.6%), (e) moderate but increasing
      depressive symptoms (8.3%), and (f) persistently high depressive symptoms (3.6%).
      Adjustment of time-varying covariates (e.g., income and health conditions)
      resulted in a similar set of distinct trajectories. Relative to White Americans,
      Black and Hispanic Americans were significantly more likely to be in trajectories
      of more elevated depressive symptoms. In addition, they were more likely to
      experience increasing and decreasing depressive symptoms. Racial and ethnic
      variations in trajectory groups were partially mediated by SES, marital status,
      and health conditions, particularly when both interpersonal and intrapersonal
      differences in these variables were taken into account.

PMID- 21875217
TI  - The relationship between cognitive function and life space: the potential role of
      personal control beliefs.
AB  - We examined the relationship of cognitive and functional measures with life space
      (a measure of spatial mobility examining extent of movement within a person's
      environment) in older adults, and investigated the potential moderating role of
      personal control beliefs. Internal control beliefs reflect feelings of competence
      and personal agency, while attributions of external control imply a more
      dependent or passive point of view. Participants were 2,737 adults from the
      ACTIVE study, with a mean age of 74 years. Females comprised 76% of the sample,
      with good minority representation (27% African American). In multiple regression
      models controlling for demographic factors, cognitive domains of memory,
      reasoning, and processing speed were significantly associated with life space (p
      < .001 for each), and reasoning ability appeared most predictive (B = .117).
      Measures of everyday function also showed significant associations with life
      space, independent from the traditional cognitive measures. Interactions between
      cognitive function and control beliefs were tested, and external control beliefs
      moderated the relationship between memory and life space, with the combination of
      high objective memory and low external control beliefs yielding the highest life
      space (t = -2.07; p = .039). In conclusion, older adults with better cognitive
      function have a larger overall life space. Performance-based measures of everyday
      function may also be useful in assessing the functional outcome of life space.
      Additionally, subjective external control beliefs may moderate the relationship
      between objective cognitive function and life space. Future studies examining the
      relationships between these factors longitudinally appear worthwhile to further
      elucidate the interrelationships of cognitive function, control beliefs, and life
      space.

PMID- 21875219
TI  - Tests of the DRYAD theory of the age-related deficit in memory for context: not
      about context, and not about aging.
AB  - Older adults exhibit a disproportionate deficit in their ability to recover
      contextual elements or source information about prior encounters with stimuli. A
      recent theoretical account, DRYAD, attributes this selective deficit to a global
      decrease in memory fidelity with age, moderated by weak representation of
      contextual information. The predictions of DRYAD are tested here in three
      experiments. We show that an age-related deficit obtains for whichever aspect of
      the stimulus subjects' attention is directed away from during encoding
      (Experiment 1), suggesting a central role for attention in producing the age
      related deficit in context. We also show that an analogous deficit can be
      elicited within young subjects with a manipulation of study time (Experiment 2),
      suggesting that any means of reducing memory fidelity yields an interaction of
      the same form as the age-related effect. Experiment 3 evaluates the critical
      prediction of DRYAD that endorsement probability in an exclusion task should vary
      nonmonotonically with memory strength. This prediction was confirmed by assessing
      the shape of the forgetting function in a continuous exclusion task. The results
      are consistent with the DRYAD account of aging and memory judgments and do not
      support the widely held view that aging entails the selective disruption of
      processes involved in encoding, storing, or retrieving contextual information.

PMID- 21875218
TI  - Genetic architecture of context processing in late middle age: more than one
      underlying mechanism.
AB  - Studies comparing young and older adults suggest a deficit in processing context
      information as a key mechanism underlying cognitive aging. However, the genetic
      architecture of context processing has not been examined. Consistent with
      previous results, we found evidence of functionally dissociable components of
      context processing accuracy in 1127 late middle-aged twins ages 51-60. One
      component emphasizes use of context cues to prepare responses (proactive
      cognitive control), and the other emphasizes adjustment of responses after probes
      are presented (reactive control). Approximately one-quarter of the variance in
      each component was accounted for by genes. Multivariate twin analysis indicated
      that genetic factors underlying two important components of context processing
      were independent of one another, thus implicating more than one underlying
      mechanism. Slower reaction time (RT) on noncontext processing trials was
      positively correlated with errors on the strongly proactive control component on
      which young adults outperform older adults, but RT was negatively correlated with
      errors on the strongly reactive control component on which older adults perform
      better. Although this RT measure was uncorrelated with chronological age in our
      age-homogeneous sample, slower RT was associated with performance patterns that
      were more like older adults. However, this did not generalize to other processing
      speed measures. Genetic correlations, which reflect shared genetic variance,
      paralleled the phenotypic correlations. There was also a positive genetic
      correlation between general cognitive ability and accuracy on the proactive
      control component, but there were still mostly distinct genetic influences
      underlying these measures. In contrast, the reactive control component was
      unrelated to general cognitive ability.

PMID- 21875221
TI  - Beery-Buktenica Developmental Test of Visual-Motor Integration performance in
      children with traumatic brain injury and attention-deficit/hyperactivity
      disorder.
AB  - Evaluation of visuoconstructional abilities is a common part of clinical
      neuropsychological assessment, and the Beery-Buktenica Developmental Test of
      Visual-Motor Integration (VMI; K. E. Beery & N. A. Beery, 2004) is often used for
      this purpose. However, few studies have examined its psychometric properties when
      used to assess children and adolescents with traumatic brain injury (TBI) or
      attention-deficit/hyperactivity disorder (ADHD), even though these are among the
      most common acquired and neurodevelopmental forms of brain dysfunction in
      children. This study examined the validity of VMI scores in 123 children with TBI
      and 65 with ADHD. The TBI and ADHD groups performed significantly worse than the
      standardization sample, obtaining VMI mean scores of 87.2 (SD = 13.7) and 93.5
      (SD = 11.27). Previous research has noted decrements in visuoconstructional
      abilities in TBI but relative sparing in ADHD. To examine the criterion validity
      of VMI scores, the authors therefore compared these 2 groups. As anticipated, the
      TBI group performed significantly worse than the ADHD group, but receiver
      operator characteristic analysis indicated that VMI scores were poor at
      discriminating between groups. Nonetheless, convergent validity evidence
      supported interpretation of VMI scores as measuring perceptual organization in
      both groups. In particular, principal components analysis indicated that VMI
      total scores loaded with perceptual organization tests from the Wechsler
      Intelligence Scale for Children, 3rd ed. (WISC-III; D. Wechsler, 1997), and its
      highest correlation was with the WISC-III Perceptual Organization Index. Also,
      the VMI correlated significantly with the Grooved Pegboard test for the group
      with TBI. These findings suggest that VMI scores are sensitive to
      visuoconstructional and motor deficits in children with developmental and
      acquired brain dysfunction.

PMID- 21875220
TI  - Psychopathic traits and externalizing behaviors: a comparison of self- and
      informant reports in the statistical prediction of externalizing behaviors.
AB  - It has long been assumed that features associated with psychopathy, such as a
      lack of insight and deceitfulness, may compromise the utility of self-report
      measures, particularly for understanding the relations between these traits and
      important outcomes (e.g., offending). Unfortunately, little research has
      explicitly examined the relations between self- and informant reports of
      psychopathy and their relations to these outcomes. The current study examined the
      incremental validity of self- and informant reports of psychopathic traits,
      assessed with 3 validated psychopathy measures, in the statistical prediction of
      externalizing behaviors (EBs). To reduce shared method variance, self- and
      informant reports of EBs (i.e., substance use, antisocial behavior, gambling, and
      intimate partner violence) were examined separately. Results indicate that both
      self- and informant reports of psychopathy are related to EBs and provide some
      degree of incremental validity, although self-reported psychopathy scores proved
      slightly more useful than other-reported psychopathy scores. These findings
      suggest that, in nonforensic settings, psychopathy data derived from both self-
      and other-reported psychopathy measures have utility in understanding the
      relations between psychopathic traits and EBs.

PMID- 21875222
TI  - Exposure to negative affect cues and urge to smoke.
AB  - While much of the cue exposure literature for cigarette smoking has focused on
      external cues, little has been done in the area of exposing participants to
      internal cues, such as negative affect (NA), despite the important role of such
      cues in maintaining smoking behavior. Smokers were exposed to an NA mood
      induction to induce an urge to smoke and then exposed to NA cues over several
      trials in an attempt to decrease this urge. Participants (N = 32) were
      undergraduate smokers assigned to either the exposure or control group for the
      mood induction procedure, which occurred over 8 trials. All participants viewed
      NA images and listened to NA music at Trial 1. The exposure group continued to
      view NA images and listened to NA music, and the control group viewed neutral
      images and listened to neutral music for 6 subsequent trials lasting about 5 min
      each. Both groups were exposed to NA images and NA music at Trial 8. NA and urge
      to smoke ratings were assessed at the end of each trial; heart rate was measured
      continuously. Results indicated that the mood induction procedure induced NA and
      urge to smoke, but the extinction procedure did not decrease urge over trials.
      Heart rate data were not associated with self-report data. In conclusion, the
      mood induction procedure in the present study appears to be an efficient way to
      induce urge to smoke. However, further research is necessary to determine why
      urge to smoke seems to be resistant to extinction.

PMID- 21875223
TI  - Effects of acute nicotine administration on resting EEG in nonsmokers.
AB  - Smoking/nicotine has been shown to increase brain arousal states, yet previous
      studies have failed to distinguish between absolute improvements due to nicotine
      versus relief from withdrawal symptoms in smokers. This study examined the
      electrocortical response to nicotine in a nonsmoking population, in order to
      negate potential withdrawal symptoms. Twenty right-handed, nonsmoking
      participants were administered nicotine (6 mg) or placebo gum within a double
      blind, repeated-measures design. In each session, EEG was recorded during a 2
      min, resting, eyes-open condition. Nicotine administration (vs. placebo) resulted
      in significantly greater frontal (specifically left-frontal) alpha2 power.
      Similar to previous findings in smokers. The absence of slow-wave changes
      following nicotine in nonsmokers suggest that these previous results in smokers
      may be related to withdrawal state.

PMID- 21875224
TI  - Expectation to receive methylphenidate enhances subjective arousal but not
      cognitive performance.
AB  - Nonmedical use of prescription-stimulant medication such as methylphenidate (MPH)
      has increased among college students over the past several years. Common
      motivations for use include enhancements in cognition and subjective arousal. As
      it is unclear whether stimulant medication exerts the same effect on healthy
      individuals as for those with attention-deficit/hyperactivity disorder, it is
      possible that many reported effects of prescription stimulants by healthy
      individuals may stem from placebo effects, which may be an important mechanism
      underlying initiation and maintenance of nonmedical use. This study examined
      whether placebo effects influence reports of subjective mood and cognitive
      performance among college students who endorsed several risk factors for
      prescription-stimulant misuse (i.e., low grade point average, fraternity/sorority
      involvement, binge drinking, cannabis use). Ninety-six subjects (60% male)
      completed cognitive tests and questionnaires assessing present mood state on two
      occasions. Forty-seven participants were randomized to an experimental condition
      and orally ingested what they believed to be MPH, though actually placebo, on one
      visit and received no medication on the other visit. The control group received
      no medication on either visit. During the administration visit, experimental
      participants reported feeling significantly more high and stimulated compared
      with the nonadministration visit and to the control subjects. However, cognitive
      enhancement differences were not generally seen between visits or groups. This
      research demonstrates that placebo effects for prescription stimulants do
      influence subjective mood and may be implicated in nonmedical stimulant use. This
      knowledge may be useful in challenging prescription-stimulant-related
      expectancies to decrease the prevalence of use among college students.

PMID- 21875226
TI  - Wanting, having, and needing: integrating motive disposition theory and self
      determination theory.
AB  - Four studies explored the motivational and experiential dynamics of psychological
      needs, applying both self-determination theory and motive disposition theory. In
      all 4 studies, motive dispositions toward achievement and affiliation ("wanting"
      particular experiences) predicted corresponding feelings of competence and
      relatedness ("having" those experiences). Competence and relatedness in turn
      predicted well-being, again indicating that these 2 experiences may really be
      "needed." Illuminating how wanting gets to having, in Studies 2 and 3,
      participants reported greater self-concordance for motive-congruent goals, which,
      in longitudinal Study 3, predicted greater attainment of those goals and thus
      enhanced well-being. Study 4 replicated selected earlier results using an
      implicit as well as an explicit motive disposition measure. Supporting the
      presumed universality of competence and relatedness needs, in no studies did
      motive dispositions moderate the effects of corresponding need-satisfaction on
      well-being. Discussion focuses on a "sequential process" model of psychological
      needs that views needs as both motives that instigate and outcomes that reward
      behavior.

PMID- 21875227
TI  - Longitudinal impact of parental and adolescent personality on parenting.
AB  - This study provides a test of how personality may shape social behaviors in a
      long-lasting dyad: the parent-adolescent relationship. In a large Belgian
      community sample, it was examined which parent Big Five characteristics were
      related to parenting and whether adolescent Big Five characteristics elicited
      certain parenting behaviors. Further, the proposition that individual differences
      are amplified under stress was examined by exploring whether parent personality
      was differentially related to parenting for parents of "easy" versus "difficult"
      adolescents. Moreover, possible differences in associations across parental and
      adolescent gender were explored. Mothers (N = 467) and fathers (N = 428) reported
      on their personality using the Five-Factor Personality Inventory; adolescents (N
      = 475) assessed their personality with the Hierarchical Personality Inventory for
      Children. Two types of parenting behaviors, overreactive discipline and warmth,
      were assessed 2 years later by parent self-reports, partner reports, and
      adolescent reports, from which multi-informant latent factors were created.
      Results indicate that parental personality was more relevant than adolescent
      personality for explaining overreactivity, but parent and adolescent personality
      were similarly relevant in explaining warmth. Especially parental and adolescent
      Agreeableness and adolescent Extraversion were important predictors of both types
      of parenting. Associations between parental personality and parenting were
      similarly related to parents of easy versus difficult adolescents, and for
      mothers and fathers parenting daughters or sons. Together, results show that
      parent characteristics as well as adolescent characteristics importantly affect
      dysfunctional and adaptive parenting.

PMID- 21875228
TI  - Stepping back to see the big picture: when obstacles elicit global processing.
AB  - Can obstacles prompt people to look at the "big picture" and open up their minds?
      Do the cognitive effects of obstacles extend beyond the tasks with which they
      interfere? These questions were addressed in 6 studies involving both physical
      and nonphysical obstacles and different measures of global versus local
      processing styles. Perceptual scope increased after participants solved anagrams
      in the presence, rather than the absence, of an auditory obstacle (random words
      played in the background; Study 1), particularly among individuals low in
      volatility (i.e., those who are inclined to stay engaged and finish what they do;
      Study 4). It also increased immediately after participants encountered a physical
      obstacle while navigating a maze (Study 3A) and when compared with doing nothing
      (Study 3B). Conceptual scope increased after participants solved anagrams while
      hearing random numbers framed as an "obstacle to overcome" rather than a
      "distraction to ignore" (Study 2) and after participants navigated a maze with a
      physical obstacle, compared with a maze without a physical obstacle, but only
      when trait (Study 5) or state (Study 6) volatility was low. Results suggest that
      obstacles trigger an "if obstacle, then start global processing" response,
      primarily when people are inclined to stay engaged and finish ongoing activities.
      Implications for dealing with life's obstacles and related research are
      discussed.

PMID- 21875225
TI  - Contributions of neuroimaging to understanding sex differences in cocaine abuse.
AB  - A consistent observation in drug abuse research is that males and females show
      differences in their response to drugs of abuse. In order to understand the
      neurobiology underlying cocaine abuse and effective treatments, it is important
      to consider the role of sex differences. Sex hormones have been investigated in
      both behavioral and molecular studies, but further evidence addressing drug abuse
      and dependence in both sexes would expand our knowledge of sex differences in
      response to drugs of abuse. Neuroimaging is a powerful tool that can offer
      insight into the biological bases of these differences and meet the challenges of
      directly examining drug-induced changes in brain function. As such, neuroimaging
      has drawn much interest in recent years. Specifically, positron emission
      tomography (PET), single photon emission computed tomography (SPECT), and
      magnetic resonance imaging (MRI) technology have emerged as effective noninvasive
      approaches for human and animal models. Studies have revealed sex-specific
      changes in patterns of brain activity in response to acute cocaine injection and
      after prolonged cocaine use. SPECT and PET studies have demonstrated changes in
      the dopamine transporter but are less clear on other components of the
      dopaminergic system. This review highlights contributions of neuroimaging toward
      understanding the role of sex differences in the drug abuse field, specifically
      regarding cocaine, and identifies relevant questions that neuroimaging can
      effectively address.

PMID- 21875229
TI  - Race is gendered: how covarying phenotypes and stereotypes bias sex
      categorization.
AB  - We argue that race and sex categories are psychologically and phenotypically
      confounded, affecting social categorizations and their efficiency. Sex
      categorization of faces was facilitated when the race category shared facial
      phenotypes or stereotypes with the correct sex category (e.g., Asian women and
      Black men) but was impaired when the race category shared incompatible phenotypes
      or stereotypes with the correct sex category (e.g., Asian men and Black women).
      These patterns were evident in the disambiguation of androgynous faces (Study 1)
      and the efficiency of judgments (Studies 1, 2, 4, and 5). These patterns emerged
      due to common facial phenotypes for the categories Black and men (Studies 3 and
      5) and due to shared stereotypes among the categories Black and men and the
      categories Asian and women (Studies 4 and 5). These findings challenge the notion
      that social categories are perceived independent of one another and show,
      instead, that race is gendered.

PMID- 21875230
TI  - Relating trait self-control and forgiveness within prosocials and proselfs:
      compensatory versus synergistic models.
AB  - The present research tested 2 competing models specifying how 2 traits (concern
      with the well-being of others and self-control) interact to predict forgiveness.
      According to the compensatory model, forgiveness requires being high on either
      trait; according to the synergistic model, forgiveness requires being high on
      both traits. Two preliminary studies demonstrated the main effect of trait (Study
      1a) and primed (Study 1b) self-control on forgiveness. Three primary studies
      consistently supported the compensatory model in predicting willingness to
      forgive a partner who behaves noncooperatively in a 2-alternative prisoner's
      dilemma (Study 2), a continuous give-some dilemma (Study 3), and a 2-alternative
      maximizing difference game (Study 4). Among proselfs or those low in trait
      forgiveness, trait self-control positively related to forgiveness, suggesting
      that self-control can compensate for a lack of concern with others' well-being.
      Implications for theory and research on forgiveness are discussed.

PMID- 21875231
TI  - Personal relative deprivation, delay discounting, and gambling.
AB  - Several lines of research have provided evidence for a relation between personal
      relative deprivation and gambling. Despite this knowledge, little is known about
      possible psychological mechanisms through which personal relative deprivation
      exerts its influence on gambling. The authors of this research sought to examine
      one such mechanism: the desire for immediate rewards. Using complementary
      approaches to studying psychological mechanisms, they tested in four studies the
      general hypothesis that personal relative deprivation translates into gambling
      urges and behavior in part via increased desires for immediate, even if smaller,
      rewards. Study 1 showed that an experimental manipulation of personal relative
      deprivation increased participants' preferences for smaller-sooner over larger
      later rewards during a delay-discounting task. Studies 2 and 3 showed that a
      decreased willingness to delay gratification led to increased gambling behavior.
      Study 4 showed that preferences for smaller-sooner over larger-later rewards
      statistically mediated the relation between self-reported personal relative
      deprivation and gambling urges among a community sample of gamblers. The
      implications and potential applications of these findings are discussed.

PMID- 21875232
TI  - Sweet taste preferences and experiences predict prosocial inferences,
      personalities, and behaviors.
AB  - It is striking that prosocial people are considered "sweet" (e.g., "she's a
      sweetie") because they are unlikely to differentially taste this way. These
      metaphors aid communication, but theories of conceptual metaphor and embodiment
      led us to hypothesize that they can be used to derive novel insights about
      personality processes. Five studies converged on this idea. Study 1 revealed that
      people believed strangers who liked sweet foods (e.g., candy) were also higher in
      agreeableness. Studies 2 and 3 showed that individual differences in the
      preference for sweet foods predicted prosocial personalities, prosocial
      intentions, and prosocial behaviors. Studies 4 and 5 used experimental designs
      and showed that momentarily savoring a sweet food (vs. a nonsweet food or no
      food) increased participants' self-reports of agreeableness and helping behavior.
      The results reveal that an embodied metaphor approach provides a complementary
      but unique perspective to traditional trait views of personality.

PMID- 21875233
TI  - Introduction to the special section: contextualizing significance testing in
      clinical trials.
AB  - The presentation and interpretation of clinical trial data is of crucial
      importance to psychotherapy research and practice. This introduction briefly
      describes how this Special Section on significance testing in clinical trials
      came about, as well as some of the content included in the articles. Between the
      original theoretical article and the four invited comments, this Special Section
      provides a concise and accessible overview of current thinking regarding the
      limitations of clinical trial data, particularly significance testing, as well as
      improvements and supplements to these analyses that may benefit both
      psychotherapy research and those who use this information in applied practice.

PMID- 21875234
TI  - Statistical significance testing and clinical trials.
AB  - The efficacy of treatments is better expressed for clinical purposes in terms of
      these treatments' outcome distributions and their overlapping rather than in
      terms of the statistical significance of these distributions' mean differences,
      because clinical practice is primarily concerned with the outcome of each
      individual client rather than with the mean of the variety of outcomes in any
      group of clients. Reports of the obtained outcome distributions for the
      comparison groups of all competently designed and executed randomized clinical
      trials should be publicly available no matter what the statistical significance
      of the mean differences among these groups, because all of these studies' outcome
      distributions provide clinically useful information about the efficacy of the
      treatments compared.

PMID- 21875235
TI  - Some more fundamental problems in clinical research: comment on "Statistical
      significance testing and clinical trials".
AB  - Comments on an article "Statistical significance testing and clinical trials" by
      Merton S. Krause (see record 2011-19228-002). The article provides a thought
      provoking and critical discussion of the conventional statistical testing in
      clinical research. Krause argues that, by focusing exclusively on mean
      differences between groups and their statistical significance, important
      information about the individual participant is being ignored. This article
      argues a few central issues with Krause's article.

PMID- 21875236
TI  - Statistical significance testing and clinical effectiveness studies.
AB  - Effectiveness studies, by definition, must reflect patient and treatment
      variables that exist in the real world of practice. This includes identifying the
      covariates that contribute to both positive and negative outcomes. The use of
      clinically significant change and reliable change indices is reviewed to
      demonstrate that patient changes can be made on the basis of normative
      comparisons, using outcome relevant variables that reflect the diversity of
      problems that are of concern to our clients. Therefore, neither agreement on a
      single outcome index nor plotting the entire outcome frequency distributions of
      the comparison group, as called for by Krause (see record 2011-19228-002), is
      required. Various methods currently exist and are used to address the limitations
      Krause cites with respect to randomized trials, outcome relevant covariates, file
      drawer effects, and so forth. The identification and prediction of an
      individual's treatment response can be done in treatment as usual studies, where
      outcome relevant covariates have not been controlled, by studying change at the
      individual level. By studying such individuals and their combined continuums of
      treatment response, we can then identify clinically relevant outcome variables
      and alter the course of treatment accordingly.

PMID- 21875237
TI  - Solving problems with randomized clinical trials is not enough to improve
      psychotherapy outcome: comments on Krause.
AB  - The problems noted by Krause (see record 2011-19228-002) with regards to
      interpreting evidence from randomized clinical trials are discussed. It is
      suggested that some of these problems have already been addressed and
      improvements made by some researchers, mainly examining the changes made by every
      patient in the treatment groups through the use of clinically significant change.
      It is suggested that regardless of the evidence-behind treatments, maximal
      patient outcome can best be obtained through formally monitoring patient
      treatment response in real time, session-by-session.

PMID- 21875238
TI  - Improving the relationship between the randomized clinical trial and real-world
      clinical practice.
AB  - I comment on the article by Krause (see record 2011-19228-002), which discusses a
      number of ways for clinical psychotherapy outcome researchers to make the results
      of randomized controlled trials (RCT) more useful to practicing psychotherapists
      primarily by making the distributions of raw data from those studies available to
      the public. In this way, it would be possible for psychotherapists to determine
      which treatment of an RCT (experimental or control) would be best for a specific
      patient. Problems with this proposal are discussed and an alternative model that
      integrates psychotherapy outcome data from group means and clinical case studies
      is offered.

PMID- 21875240
TI  - Interpersonal processes in psychodynamic-interpersonal and cognitive behavioral
      group therapy: a systematic case study of two groups.
AB  - This mixed method systematic case study applied an interpersonal stage model of
      the therapeutic process to examine interpersonal processes among a highly
      adherent Group Psychodynamic-Interpersonal Psychotherapy (GPIP) therapist and a
      highly adherent Group Cognitive Behavioral Therapy (GCBT) therapist and their
      groups of binge eating disordered (BED) patients. This is the first case study to
      apply the interpersonal stage model of psychotherapy to compare GCBT and GPIP
      methods and the first to apply the model to group therapy. Early-, middle-, and
      late-stage transcribed video recordings of sequential interactions among
      therapists and patients in each of these two time-limited group therapies were
      analyzed with the Structural Analysis of Social Behavior (SASB). We also provide
      qualitative presentations of the transcripts from each stage as context for the
      quantitative analyses. BED patients in both groups achieved positive outcomes for
      binge eating and depression. Consistent with their treatment model, the GPIP
      therapist was more autonomy-giving, whereas the GCBT therapist was more
      controlling/directive. The GPIP therapist and her group had high levels of
      interpersonal complementary interaction sequences in the early stage followed by
      lower complementarity in the middle stage. The GCBT therapist and her group
      showed a high-low-high pattern of complementarity across the three stage of
      therapy. However, overall the GPIP group had higher levels complementarity than
      the GCBT group. This mixed method case study of group processes based on an
      interpersonal stage model of psychotherapy suggested specific therapist behaviors
      in each modality to maximize positive therapeutic interactions at each stage of
      group therapy.

PMID- 21875243
TI  - Mechanisms of developmental regression in autism and the broader phenotype: a
      neural network modeling approach.
AB  - Loss of previously established behaviors in early childhood constitutes a
      markedly atypical developmental trajectory. It is found almost uniquely in autism
      and its cause is currently unknown (Baird et al., 2008). We present an artificial
      neural network model of developmental regression, exploring the hypothesis that
      regression is caused by overaggressive synaptic pruning and identifying the
      mechanisms involved. We used a novel population-modeling technique to investigate
      developmental deficits, in which both neurocomputational parameters and the
      learning environment were varied across a large number of simulated individuals.
      Regression was generated by the atypical setting of a single pruning-related
      parameter. We observed a probabilistic relationship between the atypical pruning
      parameter and the presence of regression, as well as variability in the onset,
      severity, behavioral specificity, and recovery from regression. Other
      neurocomputational parameters that varied across the population modulated the
      risk that an individual would show regression. We considered a further hypothesis
      that behavioral regression may index an underlying anomaly characterizing the
      broader autism phenotype. If this is the case, we show how the model also
      accounts for several additional findings: shared gene variants between autism and
      language impairment (Vernes et al., 2008); larger brain size in autism but only
      in early development (Redcay & Courchesne, 2005); and the possibility of quasi
      autism, caused by extreme environmental deprivation (Rutter et al., 1999). We
      make a novel prediction that the earliest developmental symptoms in the emergence
      of autism should be sensory and motor rather than social and review empirical
      data offering preliminary support for this prediction.

PMID- 21875244
TI  - Uncertainty forecasts improve weather-related decisions and attenuate the effects
      of forecast error.
AB  - Although uncertainty is inherent in weather forecasts, explicit numeric
      uncertainty estimates are rarely included in public forecasts for fear that they
      will be misunderstood. Of particular concern are situations in which
      precautionary action is required at low probabilities, often the case with severe
      events. At present, a categorical weather warning system is used. The work
      reported here tested the relative benefits of several forecast formats, comparing
      decisions made with and without uncertainty forecasts. In three experiments,
      participants assumed the role of a manager of a road maintenance company in
      charge of deciding whether to pay to salt the roads and avoid a potential penalty
      associated with icy conditions. Participants used overnight low temperature
      forecasts accompanied in some conditions by uncertainty estimates and in others
      by decision advice comparable to categorical warnings. Results suggested that
      uncertainty information improved decision quality overall and increased trust in
      the forecast. Participants with uncertainty forecasts took appropriate
      precautionary action and withheld unnecessary action more often than did
      participants using deterministic forecasts. When error in the forecast increased,
      participants with conventional forecasts were reluctant to act. However, this
      effect was attenuated by uncertainty forecasts. Providing categorical decision
      advice alone did not improve decisions. However, combining decision advice with
      uncertainty estimates resulted in the best performance overall. The results
      reported here have important implications for the development of forecast formats
      to increase compliance with severe weather warnings as well as other domains in
      which one must act in the face of uncertainty.

PMID- 21875245
TI  - A frog in your throat or in your ear? Searching for the causes of poor singing.
AB  - Singing is a cultural universal and an important part of modern society, yet many
      people fail to sing in tune. Many possible causes have been posited to explain
      poor singing abilities; foremost among these are poor perceptual ability, poor
      motor control, and sensorimotor mapping errors. To help discriminate between
      these causes of poor singing, we conducted 5 experiments testing musicians and
      nonmusicians in pitch matching and judgment tasks. Experiment 1 introduces a new
      instrument called a slider, on which participants can match pitches without using
      their voice. Pitch matching on the slider can be directly compared with vocal
      pitch matching, and results showed that both musicians and nonmusicians were more
      accurate using the slider than their voices to match target pitches, arguing
      against a perceptual explanation of singing deficits. Experiment 2 added a self
      matching condition and showed that nonmusicians were better at matching their own
      voice than a synthesized voice timbre, but were still not as accurate as on the
      slider. This suggests a timbral translation type of mapping error. Experiments 3
      and 4 demonstrated that singers do not improve over multiple sung responses, or
      with the aid of a visual representation of pitch. Experiment 5 showed that
      listeners were more accurate at perceiving the pitch of the synthesized tones
      than actual voice tones. The pattern of results across experiments demonstrates
      multiple possible causes of poor singing, and attributes most of the problem to
      poor motor control and timbral-translation errors, rather than a purely
      perceptual deficit, as other studies have suggested.

PMID- 21875247
TI  - Predicting the future as Bayesian inference: people combine prior knowledge with
      observations when estimating duration and extent.
AB  - Predicting the future is a basic problem that people have to solve every day and
      a component of planning, decision making, memory, and causal reasoning. In this
      article, we present 5 experiments testing a Bayesian model of predicting the
      duration or extent of phenomena from their current state. This Bayesian model
      indicates how people should combine prior knowledge with observed data. Comparing
      this model with human judgments provides constraints on possible algorithms that
      people might use to predict the future. In the experiments, we examine the
      effects of multiple observations, the effects of prior knowledge, and the
      difference between independent and dependent observations, using both
      descriptions and direct experience of prediction problems. The results indicate
      that people integrate prior knowledge and observed data in a way that is
      consistent with our Bayesian model, ruling out some simple heuristics for
      predicting the future. We suggest some mechanisms that might lead to more
      complete algorithmic-level accounts.

PMID- 21875246
TI  - Why does working memory capacity predict variation in reading comprehension? On
      the influence of mind wandering and executive attention.
AB  - Some people are better readers than others, and this variation in comprehension
      ability is predicted by measures of working memory capacity (WMC). The primary
      goal of this study was to investigate the mediating role of mind-wandering
      experiences in the association between WMC and normal individual differences in
      reading comprehension, as predicted by the executive-attention theory of WMC
      (e.g., Engle & Kane, 2004). We used a latent-variable, structural-equation-model
      approach, testing skilled adult readers on 3 WMC span tasks, 7 varied reading
      comprehension tasks, and 3 attention-control tasks. Mind wandering was assessed
      using experimenter-scheduled thought probes during 4 different tasks (2 reading,
      2 attention-control). The results support the executive-attention theory of WMC.
      Mind wandering across the 4 tasks loaded onto a single latent factor, reflecting
      a stable individual difference. Most important, mind wandering was a significant
      mediator in the relationship between WMC and reading comprehension, suggesting
      that the WMC-comprehension correlation is driven, in part, by attention control
      over intruding thoughts. We discuss implications for theories of WMC, attention
      control, and reading comprehension.

PMID- 21875248
TI  - Dissociation of short-term forgetting from the passage of time.
AB  - In many theories, forgetting is closely linked to the passage of time. In the
      present experiments, recall in a short-term memory task was less accurate when
      the retention interval included a difficult arithmetic addition task, compared
      with an easy task. In a novel condition, the interfering task was switched from
      hard to easy partway through the retention interval. Recall accuracy at long
      retention intervals recovered from the level consistent with the hard interfering
      task to a more accurate level consistent with an easy interfering task. Such
      recovery is not in agreement with theories that link forgetting to the passage of
      time, such as trace decay. The reversed forgetting functions are more consistent
      with an account in which different levels of nonspecific retroactive interference
      in the retention interval just before the time of retrieval influence different
      levels of performance accuracy. With the uncoupling of interference levels from
      time, forgetting is dissociated from the passage of time.

PMID- 21875249
TI  - Retrieval-induced forgetting of arithmetic facts.
AB  - Retrieval-induced forgetting (RIF) is a widely studied phenomenon of human
      memory, but RIF of arithmetic facts remains relatively unexplored. In 2
      experiments, we investigated RIF of simple addition facts (2 + 3 = 5) from
      practice of their multiplication counterparts (2 * 3 = 6). In both experiments,
      robust RIF expressed in response times occurred only for high-strength small
      number addition facts with sums <= 10, indicating that RIF from multiplication
      practice was interference dependent. RIF of addition-fact memory was produced by
      multiplication retrieval (2 * 3 = ?) but not multiplication study (2 * 3 = 6),
      supporting an inhibitory mechanism of RIF in arithmetic memory. Finally, RIF
      occurred with multiplication practiced in word format (three * four) and addition
      tested later in digit format (3 + 4), which provides evidence that digit and
      written-word formats for arithmetic accessed a common semantic retrieval network.
      The results support the view that addition and multiplication facts are stored in
      an interrelated semantic network and that RIF of competing addition facts is an
      intrinsic process of multiplication fact retrieval.

PMID- 21875250
TI  - What factors underlie associative and categorical memory illusions? The roles of
      backward associative strength and interitem connectivity.
AB  - Factors that affect categorical and associative false memory illusions were
      investigated in 2 experiments. In Experiment 1, backward associative strength
      (BAS) from the list word to the critical lure and interitem connectivity were
      manipulated in Deese-Roediger-McDermott (DRM) and category list types. For both
      recall and recognition tasks, the likelihood of producing DRM and category false
      memories was greater for lists with high BAS and low interitem connectivity. In
      Experiment 2, DRM and category lists with high BAS showed similar indirect
      priming effects in a word stem completion task. With low BAS, category lists,
      unlike DRM lists, showed no priming effect. We discuss the role of BAS, interitem
      connectivity, and associate-level differences in implicit and explicit measures
      of false memory production.

PMID- 21875251
TI  - Reasoning about other people's beliefs: bilinguals have an advantage.
AB  - Bilingualism can have widespread cognitive effects. In this article we
      investigate whether bilingualism might have an effect on adults' abilities to
      reason about other people's beliefs. In particular, we tested whether bilingual
      adults might have an advantage over monolingual adults in false-belief reasoning
      analogous to the advantage that has been observed with bilingual children. Using
      a traditional false-belief task coupled with an eye-tracking technique, we found
      that adults in general suffer interference from their own perspective when
      reasoning about other people's beliefs. However, bilinguals are reliably less
      susceptible to this egocentric bias than are monolinguals. Moreover, performance
      on the false-belief task significantly correlated with performance on an
      executive control task. We argue that bilinguals' early sociolinguistic
      sensitivity and enhanced executive control may account for their advantage in
      false-belief reasoning.

PMID- 21875252
TI  - Not all skilled readers have cracked the code: individual differences in masked
      form priming.
AB  - This experiment investigated whether individual differences in written language
      proficiency among university students predict the early stages of lexical
      retrieval tapped by the masked form priming lexical decision task. To separate
      the contributions of sublexical facilitation and lexical competition to masked
      form priming, the effects of prime lexicality were directly compared for both
      transposed-letter (TL) primes (e.g., sung SNUG; salb SLAB) and neighbor primes
      (e.g., snag SNUG; sleb SLAB) in a sample of 100 university students assessed on
      measures of reading, spelling and vocabulary. The data for the whole sample
      showed facilitation from nonword primes, but inhibition from word primes. Linear
      mixed models including the individual difference measures showed that higher
      scores on a principal component that captured the shared variance among reading,
      spelling, and vocabulary were associated with both stronger inhibition from TL
      word primes and stronger facilitation from neighbor nonword primes. These
      findings are consistent with the lexical quality hypothesis of reading that
      predicts that skilled readers vary in the extent to which they have developed
      precisely specified orthographic representations.

PMID- 21875253
TI  - The present scenario of cervical cancer control and HPV epidemiology in India: an
      outline.
AB  - OBJECTIVE: To give a clear picture with epidemiological evidence about the
      present scenario of cervical cancer control and HPV in India. DESIGN: Review of
      published studies, concentrating on recent systematic reviews, meta-analyses and
      large prospective studies. CONCLUSIONS AND RECOMMENDATIONS: Cervical cancer is
      unique among cancers in that it can largely be prevented through screening and
      removal of precursor lesions. It is the second most common cancer among women
      worldwide and is the most common malignancy in developing countries, particularly
      in India. Nowadays, cervical screening for women is necessary because there are
      no signs and symptoms of cervical precancers. The establishment of a prevention
      program is urgently required considering both screening and vaccination. But most
      women in India do not have access to effective screening programmes. It has been
      estimated that in India, even with a major effort to expand cytology services, it
      will not be possible to screen even one-fourth of the population once in a
      lifetime in the near future. New HPV vaccines will also help prevent HPV
      infection and the precancerous changes that lead to cervical cancer. The focus on
      detection and prevention of cervical cancer must be emphasized in a highly
      populated country like India to prevent its extensive spread.

PMID- 21875254
TI  - Circulating miRNAs: promising biomarkers of human cancer.
AB  - BACKGROUND: With the development of technologies to look at the expression levels
      of hundreds of miRNAs at a time and the clear role of miRNAs in cancers, groups
      began looking at miRNAs profiles of different cancers, especially the circulating
      miRNAs. We intended to make sure whether circulating miRNAs could be a promising
      biomarker of human cancers. METHOD: We comprehensively searched the Cochrane
      Library, Medline and EMbase from 1966 to Nov 2009 for the following terms:
      ("miRNA" or "microRNA") and ("tumor" or "carcinoma") and ("plasma*" or "serum" or
      "circulating"). Detailed information was extracted from studies that met the
      inclusion criteria: blood-based miRNAs in human cancers and studies published in
      the English literature. RESULTS: The current review show that different
      researches use different measurement methods which might impact the results;
      Cancers treatment might have an affect on circulating miRNAs; some miRNAs are
      multi-faceted RNA; small sample size might produce selection bias. Furthermore,
      because of the lack of randomized controlled trials and the heterogeneous nature
      of the available data, no attempt was made to perform quantitativemeta-analyses.
      CONCLUSIONS: In this review, based on those researches, circulating miRNAs are
      promising and difficulties for their future application for diagnosing human
      cancers.

PMID- 21875255
TI  - Genomics and pharmacogenomics of breast cancer: current knowledge and trends.
AB  - The impact of genomics and pharmacogenomics in the current arena of clinical
      oncology is well-established. In breast cancer, mutations in the BRCA1 and BRCA2
      genes have been well-characterized to carry a high risk of the disease during a
      woman's lifespan. However, these high risk genes contribute to only a small
      proportion of the familial cases of breast cancer. Hence, further efforts aimed
      to study the contribution of genetic mutations in other genes, including the
      estrogen receptor gene, TP53, CYP19, and mismatch repair genes to further
      investigate the genetic component of breast cancer. Multiple pharmacogenomic
      studies have previously linked genetic variants in known pathways with treatment
      response in cancer patients. Currently, polymorphisms in drug metabolizing
      enzymes, efflux transporters, as well as, drug targets have shown correlations to
      variations in response and toxicity to commonly prescribed chemotherapeutic
      treatments of breast cancer. CYP2D6 variants have been correlated with tamoxifen
      response and interindividual variability seen. An emerging application of cancer
      genetics and pharmacogenetics involves the use of inherited or acquired genetic
      abnormalities to predict treatment toxicity or outcomes. Recently, methods that
      involve the scanning of entire genomes for common variants have begun to
      influence studies of cancer causation. Currently, treatment individualization for
      breast cancer can take place on the basis of few molecular targets including the
      estrogen receptor and the overexpression of the HER2 receptor. Overall, the
      current review summarizes the recent findings in the genetic and pharmacogenetic
      research of breast cancer and the advances made in personalization of treatment.

PMID- 21875256
TI  - Histopathological classification of nasopharyngeal carcinoma.
AB  - This article reviews all related research and reports on nasopharyngeal cancer
      (NPC) histopathological classifications worldwide. Despite continuous advance of
      Chinese and international NPC histopathological classification research, it was
      difficult to unify previous with current China classifications, and the China
      with World Health Organization (WHO) classifications. For example, non
      keratinizing and undifferentiated carcinoma of the WHO NPC classification does
      not coincide with poorly-differentiated squamous cell carcinoma of the previous
      China classification. In addition, the incidence rates of different NPC
      pathological types show obvious regional discrepancies. It suggested that for
      facilitating Chinese and international NPC research and exchange, NPC
      histopathological classifications worldwide should be effectively unified.

PMID- 21875257
TI  - Review of the cervical cancer disease burden in mainland China.
AB  - Human papillomavirus (HPV) infection is a common sexually transmitted infection
      (STI) worldwide. HPV may cause several reproductive tract diseases and cervical
      cancer is the most serious health problem due to persistent high risk HPV
      infection. Although cervical cancer showed a declining trend over the past three
      decades in China, it remains a major health problem in Chinese women especially
      women living in rural China. The disease burden is believed to be underestimated
      given the relatively high HPV prevalence shown in recent studies. To date,
      prophylactic vaccination as a primary prevention of cervical cancer are available
      in many countries and regions of the world; yet, they are not yet accessible in
      mainland China. Before introduction of HPV vaccines, screening remains the
      predominant method of prevention. Selected population based screening sites are
      available in every province of China, yet, an organized screening program
      operating nationwide still does not exist. A better understanding of the disease
      burden is likely to help develop a comprehensive intervention policy for future
      management of cervical cancer in China. It is important to review the disease
      burden of cervical cancer and the current status of cervical cancer screening in
      mainland China.

PMID- 21875258
TI  - Malignant pleural mesothelioma in Singapore.
AB  - AIM: To examine the clinical characteristics and outcomes of malignant pleural
      mesothelioma (MPM) in Singapore. METHODS AND MATERIALS: A retrospective case note
      review of patients diagnosed with MPM between 1997 and 2007. Overall survival
      (OS), locoregional recurrence-free survival (LRS) and metastasis-free survival
      (MFS) were estimated using Kaplan Meier method and comparison were done using log
      rank test. Multivariate analysis was not done due to the small number of
      patients. RESULTS: There were 39 patients diagnosed with MPM. Fifty-nine percent
      of patients presented with Stage III and IV disease. Eight (21%) patients had
      surgery with 2 patients receiving trimodality treatment and adjuvant chemotherapy
      respectively. Three patients received adjuvant RT and one patient had no adjuvant
      therapy. Twelve patients received palliative RT or chemotherapy. Median follow-up
      was 27.0 weeks. Median overall survival (OS) for all patients was 8.0 months (95%
      CI 6.3-9.7). One-year and 2-year OS were 25.6% and 6.4% respectively. Thirty
      eight patients died of progressive disease and one patient died of other cause.
      Locoregional recurrences and distant metastases occurred in 3/8 and 5/8
      surgically treated patients respectively. Overall, distant metastases occurred in
      44% of patients. Surgery did not affect survival outcomes although patients with
      dual modality treatment showed a trend towards improved survival. Epithelioid
      tumours had better prognosis (median OS 10.2 months) compared to biphasic (median
      OS 8.0 months) and sarcomatoid tumours (median OS 1.4 months). CONCLUSION: Future
      management of MPM will need to emphasize on both locoregional and systemic
      control and hence, inclusion of patients in clinical trials for multimodality
      treatment should be encouraged.

PMID- 21875259
TI  - Combined effects of isothiocyanate intake, glutathione S-transferase
      polymorphisms and risk habits for age of oral squamous cell carcinoma
      development.
AB  - Dietary isothiocyanates (ITCs) found in cruciferous vegetables (Brassica spp.)
      has been reported to reduce cancer risk by inducing phase II conjugating enzymes,
      in particular glutathione S-transferases (GSTs). This case-control study was
      aimed at determining associations between dietary ITCs, GSTs polymorphisms and
      risk habits (cigarette smoking, alcohol drinking and betel-quid chewing) with
      oral cancer in 115 cases and 116 controls. Information on dietary ITC intake from
      cruciferous vegetables was collected via a semi-quantitative food frequency
      questionnaire (FFQ). Peripheral blood lymphocytes were obtained for genotyping of
      GSTM1, GSTT1 and GSTP1 using PCR multiplex and PCR-RFLP. Chi-square and logistic
      regression were performed to determine the association of ITC and GSTs
      polymorphism and risk of oral cancer. When dietary ITC was categorized into high
      (greater than/equal to median) and low (less than median) intake, there was no
      significant difference between cases and control group. Logistic regression
      yielding odd ratios resulted in no significant association between dietary ITC
      intake, GSTM1, GSTT1 or GSTP1 genotypes with oral cancer risk overall. However,
      GSTP1 wild-type genotype was associated with later disease onset in women above
      55 years of age (p= 0.017). Among the men above 45 years of age, there was
      clinical significant difference of 17 years in the age of onset of oral cancer
      between GSTP1 wild-type + low ITC intake and GSTP1 polymorphism + high ITC intake
      (p= 0.001). Similar conditions were also seen among men above 45 years of age
      with risk habits like drinking and chewing as the earlier disease onset
      associated with GSTP1 polymorphism and high ITC intake (p< 0.001). This study
      suggests that combination effects between dietary ITCs, GSTP1 polymorphism and
      risk habits may be associated with the risk of oral cancer and modulate the age
      of disease onset.

PMID- 21875260
TI  - Clinical significance of human telomerase RNA gene (hTERC) amplification in
      cervical squamous cell lesions detected by fluorescence in situ hybridization.
AB  - BACKGROUND: Genomic amplification of the human telomerase RNA gene (hTERC),
      located in the chromosome 3q26 region, has been documented in tumorigenesis. The
      present study was designed to detect hTERC amplification in cervical lesions and
      evaluate whether this might serve as a supportive biomarker to cytopathology or
      histopathology in the diagnosis of cervical lesions. METHODS: Liquid-based thin
      layer cytopathologic examination and detection of amplification by fluorescence
      in situ hybridization (FISH) was conducted in 130 women, along with assessment of
      human papillomavirus DNA, colposcopy with biopsy, and histopathologic
      examination. RESULTS: In cytopathologic examinations, hTERC amplification rates
      for negative for intraepithelial lesion or malignancy (NILM),atypical squamous
      cells of undetermined significance (ASCUS), low-grade squamous intraepithelial
      lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL) and squamous
      cell carcinoma (SCC) cases were 0% (0/10), 4% (1/25), 20% (6/30), 77% (27/35),
      and 100% (10/10), respectively. The difference among abnormal cellular change
      groups was statistically significant (P< 0.05). In histopathologic examinations,
      hTERC amplification rates in normal squamous cell with or without inflammatory,
      cervical intraepithelial neoplasia 1 (CIN 1), CIN 2, CIN 3 and SCC cases were
      3.8% (2/52), 18.2% (6/33), 66.7% (6/9), 84.6% (22/26), 100% (10/10),
      respectively. There were significant differences among CIN1, CIN2, CIN3 and SCC
      cases (P< 0.05). The hTERC amplification was more specific than HPV positivity in
      differentiating lowgrade from high-grade cervical disorders (specificity: 88.5%
      vs. 70.8%, P< 0.05). CONCLUSIONS: FISH detection of hTERC amplification could be
      an effective adjunct to cytopathologic or histopathologic examination for
      differential diagnosis of low- and high-grade cervical squamous cell disorders.

PMID- 21875261
TI  - Practice and barriers toward breast self-examination among young Malaysian women.
AB  - INTRODUCTION: The etiology of breast cancer is still unknown and adequate primary
      prevention strategies or interventions are still not possible. Therefore, early
      detection remains the first priority and regular practice of breast self
      examination (BSE) influences treatment, quality of life, survival, and prognosis
      of breast cancer patients. OBJECTIVES: The objective of this study was to
      determine the practices and barriers towards breast self-examination among young
      Malaysian women. METHODOLOGY: Cross-sectional study was conducted among 251
      female students at the Management and Science University, Shah Alam, Selangor,
      Malaysia. Questionnaires were distributed at gathering places such as the
      university cafeteria, the university plaza, the Islamic center, and at the
      library. In addition, questionnaires were distributed in the lecture halls. The
      proposal of this study was approved by the Ethics and Research Committee of
      Management and Science University. Data was analysis using SPSS version 13, t
      test was used to analyze the associated factors toward the practice of BSE.
      RESULTS: A total number of 251 students participated in this study. The majority
      of them were older than 20 years old,of Malay racial origin, single and from
      urban areas (66.5%; 63.7%; 96%; 70.9% respectively). Regarding their lifestyle
      practices, the majority of participants do exercise, are non-smokers and do not
      drink alcohol (71.3%; 98.4%; 94.4% respectively). More than half of the study
      participants mentioned that they have practiced BSE (55.4%). Regarding the
      sources of information about BSE, the majority mentioned that radio and TV were
      their main sources of information (38.2%). Age, exercise and family history of
      cancer significantly influenced the practice of BSE (p = 0.045; p=0.002; p=0.017
      respectively). Regarding the barriers to BSE, the majority who never practiced
      BSE mentioned that lack of knowledge, not having any symptoms, and being afraid
      of being diagnosed with breast cancer were the main barriers to practicing BSE
      (20.3%; 14.3%; 4.4% respectively). CONCLUSION: More than half of the participants
      practiced BSE. Age, exercise and family history of cancer significantly
      influenced the practice of the BSE. Lack of knowledge, not having any symptoms
      and being afraid of being diagnosed with breast cancer were the main barriers to
      practicing BSE. There is an urgent need to develop a continuous awareness
      campaign among university students on the importance of performing BSE.

PMID- 21875262
TI  - Examination with the health belief model of women's attitudes to cervical cancer
      and early diagnosis in Turkey: a qualitative study.
AB  - OBJECTIVE: The study was planned with the purpose of examining women's attitude
      to the health belief model, and their attitudes and behavior towards cervical
      cancer and early diagnosis. MATERIALS AND METHODS: The qualitative (case-study)
      method was used in this study. Data were collected between October 2010 and
      November 2010 using a purposive sampling method for qualitative research. The
      study sample constituted from 11 women being treated at two clinics, between the
      ages of 15 and 49, who were married, and who had not previously had a pap-smear
      test. Data collection tool consist of two parts that are an "Information Form"
      identifying women and semi-structured "Interview Form". Interviews were done face
      to face by using in-depth interviews technique. Semi-structured interview was
      recorded in audio recording device. Content analysis method was used to assess
      the data. RESULTS: Awareness is insufficient that of women about cervical cancer
      prevention and early diagnosis, there is less fear of cervical cancer.
      Information of women is inadequate about early diagnosis and prevention of
      cervical cancer and there are various barriers about early detection and
      prevention. According to content analysis, three main themes emerge. These are
      the themes of belief, knowledge and barriers. CONCLUSIONS: It became clear from
      interviews carried out in line with the health belief model why women did not
      exhibit positive health behavior. It is recommended that this study should be
      repeated in other parts of Turkey. In addition, this study can serve as a guide
      to quantitative studies in wider communities.

PMID- 21875263
TI  - Weekly cisplatin versus standard three-weekly cisplatin in concurrent
      chemoradiotherapy of head and neck cancer: the Baskent University experience.
AB  - BACKGROUND: The majority of patients with head and neck cancer are treated with
      concurrent chemoradiotherapy. However, toxicity is substantial so that alternate
      schedules of cisplatin have been tried to overcome this problem. No formal
      comparison, however, has been reported between alternate schedules and reference
      regimen. PATIENTS AND METHODS: Fifty-five eligible patients treated with
      concurrent chemoradiotherapy were retrospectively analyzed. The patients treated
      with weekly cisplatin were defined as group A, while the patients treated with
      standard regimen were defined as group B. Basic demographics and clinical
      characteristics', overall survival rate, locoregional or systemic relapse rates,
      and time to local/systemic relapse were recorded. RESULTS: One, two, and three
      year probability of survival in groups A and B were 75% to 65% after one year,
      63% to 56%after two, and 63% to 52% after three, respectively. Although time to
      local and systemic relapse was higher in group B as compared to group A, a
      statistical analysis was failed to show any significant difference. Furthermore,
      there was no significant difference between groups with respect to major
      toxicity. CONCLUSION: In patients with head and neck cancer, concurrent
      chemoradiotherapy with weekly cisplatin might be as effective as concurrent
      chemoradiotherapy with bolus cisplatin.

PMID- 21875264
TI  - Marking non-palpable breast masses with injected methylene blue dye, an easy,
      safe and low cost method for developing countries and resource-limited areas.
AB  - INTRODUCTION: The widespread use of improved mammographic techniques has led to
      increased detection of nonpalpable breast masses. Preoperative localization is
      important for reducing false negative results and decreasing the size of tissue
      resection needed and the resulting breast deformity. We used ultrasound guided
      methylen blue injection in the mass for localization of breast masses that were
      clinically nonpalpable but detectable by ultrasound. MATERIALS AND METHODS: 57
      masses from 51 patients were marked 20 to 180 minutes before surgery with 0.4-0.7
      cc methylene blue and resection was done in operating room under local or general
      anesthesia . success of radiologist for localization and success of surgeon for
      complete resection and pathology results were reviwed and fallow up ultrasound
      was done 3-5 month after surgery for patients whom pathology report was non
      specific (such as FCC) to confirm complete resection. RESULTS: 57 masses were
      excised successfully by the surgeon , localization was successful in all patients
      but injection in the mass was not feasible in 4 patients and dye was injected on
      the surface of the mass and led to successful excision .Only one mass was not
      found at surgery because dye washed out before surgery, and the mass was resected
      by use of intra operative ultrasound. 5.3% patients reported the procedure was
      painful and 28% reported tolerable pain during injection and 66.7 % of patients
      said that the injection was painless or with minimal discomfort. Allergic
      reaction was not seen in any patient and no interference was reported by the
      pathologist in slide preparation or diagnoses and IHC study. CONCLUSION: Marking
      with blue dye injection is a safe and low cost method for localization of non
      palpable breast lesions that are detectable by Ultrasound. In one patient failure
      to find the mass was because of location of the mass that was in axillary tail of
      breast and time of surgery that was 100 minutes after injection that led to
      absorption of blue dye before surgery and it is advised to do surgery as soon as
      possible after blue dye injection especially in peripheral and deeply located
      masses.

PMID- 21875266
TI  - Apoptosis induction in MDA-MB-435S, Hep3B and PC-3 cell lines by Rheum emodi
      rhizome extracts.
AB  - The study was aimed at evaluating apoptosis induction potentials of methanolic
      and aqueous extracts of Rheum emodi Wall. ex Meissn. rhizome. The ability of the
      extracts to induce apoptosis in MDA-MB-435S (human breast carcinoma), Hep3B
      (human hepatocellular carcinoma) and PC-3 (human prostate cancer) cell lines were
      tested by ELISA to detect cellular DNA fragmentation. Results obtained from the
      present study confirm that the extracts target the cancerous cells towards
      apoptosis. The study concludes that R. emodi possess anticancer metabolites that
      can be isolated and used as precursors in development of anticancer drugs.
      Suppression of apoptosis might contribute to tumor development by means of
      accumulation of continuously proliferating cells. The strategy employed in this
      study, to induce apoptosis in the tumor cells, could be a potential target of
      therapeutic intervention of cancers.

PMID- 21875267
TI  - Factors affecting prostate cancer screening behaviour in a discrete population of
      doctors at the University Hospital of the West Indies, Jamaica.
AB  - To determine the knowledge, attitudes and practices of Jamaican male medical
      consultants regarding prostate cancer screening in three departments within the
      University Hospital of the West Indies. The research design was a cross-sectional
      quantitative survey utilising a self administered questionnaire. All 36 male
      consultants between 40 and 70 years from the Departments of Surgery Radiology
      Anaesthesia and Intensive Care, Obstetrics and Gynaecology/Child Health, and
      Medicine participated in the survey. Bivariate analyses were used to determine
      the relationship between the three constructs with P < 0.05 taken as
      statistically significant. The majority (97%) of the respondents were aware that
      prostate cancer among Jamaicans account for one of the highest incidences in the
      world and 85% believed that screening for prostate cancer should begin at age 40
      years. Approximately two-fifths (44.4%) reported that they usually encourage
      their patients to be screened. Nearly all (97%) of the respondents agreed that
      performing both the prostate specific antigen (PSA) test and digital rectal
      examination (DRE) are more effective in assessing for the presence of prostate
      cancer. Just over one-third (36%) found the DRE embarrassing and 41% had never
      had a DRE. The results showed a significant positive correlation (r = 0.374, P =
      0.032) between knowledge and attitude, and an even stronger correlation between
      attitude and prostate cancer screening practice (r = 0.395, P = 0.025). However
      there was no direct correlation between knowledge and practice. Physicians'
      knowledge of prostate cancer does not predict their personal prostate cancer
      screening behaviour. Knowledge of prostate cancer is not enough to result in
      screening behavior of men in Jamaica.

PMID- 21875265
TI  - Season of birth and risk of endometrial cancer.
AB  - OBJECTIVES: Season of birth has been associated with adult morbidity and
      mortality, but few epidemiological studies have examined whether season of birth
      contributes to the development of cancer. Using data from the Australian National
      Endometrial Cancer Study, a population-based case-control study of 1399 cases and
      1539 controls, we examined the association between season of birth and risk of
      endometrial cancer. METHODS: Unconditional logistic regression was used to
      estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the
      association between season of birth and endometrial cancer. Additional analyses
      were stratified by state of birth. RESULTS: Season of birth was not associated
      with endometrial cancer overall, but there was an increased risk among women born
      in summer in Tasmania, the most southerly state (OR = 4.46, 95% CI: 1.24-16.06)
      and non-significant increases in the other southern states. CONCLUSION: Further
      data are required to confirm these findings, however the observed associations
      may be due to the longer days and/or greater hours of sunshine in Australia's
      southerly states in summer, suppressing melatonin levels in summer-born infants
      and predisposing them to cancer in adulthood.

PMID- 21875268
TI  - Salt taste preference, sodium intake and gastric cancer in China.
AB  - AIM: The risk factors mostly strongly associated with gastric cancer are gastric
      bacteria Helicobacter pylori and diet. By using a case-control study among
      residents in China, we examined the association between sodium intake, presence
      of H,pylori, and gastric cancer risk. METHODS: A population-based case-control
      study including 235 cases and 410 controls were used. Potential risk factors of
      gastric cancer were interview for cases and controls by questionnaire, salt taste
      preference was measured for all subjects, and IgG antibodies to H,pylori was used
      for H.pylori infection. Risk measures were calculated using unconditional
      logistic regression. RESULTS: H.pylori infection and smoking increased the risk
      of gastric cancer, with the OR(95%CI) of 1.91(1.32-2.79) and 1.47(1.05- 2.05),
      respectively. Dietary sodium intake independently increased the risk of gastric
      cancer. Participants with the highest sodium intake(>5g/day) had a high gastric
      cancer risk [OR(95%CI)= 3.78(1.74-5.44)]. Participants with the salt taste
      preference at 7.3g/L and >= 14.6g/L showed higher risk of gastric cancer [OR(95%)
      for 7.3g/L and >= 14.6g/L were 5.36(2.72-10.97) and 4.75(2.43-8.85),
      respectively]. A significantly interaction was found between salt taste
      preference and H.pylori infection (p=0.037). Salt taste preference was
      significantly correlated with sodium intake (Correlation coefficient=0.46, p<
      0.001). CONCLUSION: Salt taste preference test could be a simple way to evaluate
      an inherited characteristic of sodium intake, and our study confirms the gastric
      cancer is associated with sodium intake and H.pylori.

PMID- 21875269
TI  - The need to incorporate routine cervical cancer counselling and screening in the
      management of HIV positive women in Nigeria.
AB  - OBJECTIVE: The study aimed to assess the awareness and utilization of the Pap
      smear among HIV positive women in Lagos, Nigeria. MATERIALS AND METHODS: A
      descriptive cross sectional survey of women attending the anti-retroviral clinic
      of the Lagos State University Teaching Hospital, Ikeja, Lagos State, Nigeria was
      carried out between 1st September and 30th November 2009 using a pre-tested
      questionnaire. Data were analysed using the Epi-info 3.5 statistical software of
      the Centre for Disease Control and Prevention, Atlanta USA. RESULTS: None of the
      300 respondents reported having received any form of counselling about cervical
      cancer and screening during the post HIV test counseling. Seventy six (25.3%) of
      them had heard of cervical cancer; Forty eight (16%) were aware of the Pap smear
      and only 15 (31.3%) of these (5% of the total number of respondents) have ever
      done the test before. The majority (69.7%) of those who had not been screened
      despite knowledge of the Pap smear, gave non- recommendation by their doctor as
      the main reason for not doing the test. CONCLUSION: Cervical cancer counseling
      and screening is not part of the routine management of HIV positive women in
      Lagos, Nigeria. There is need to address this deficiency with appropriate
      guidelines.

PMID- 21875270
TI  - Epidemiological study of risk factors for oral, laryngeal and esophageal cancers
      at a tertiary care hospital in India.
AB  - BACKGROUND AND AIS: An epidemiological shift in the form of increase in the
      incidence of cancer and decrease in the incidence of smoking is universally
      realized today. This study was conducted to observe an association of smoking,
      use of alcohol and tobacco and cancers of the oral cavity, larynx and esophagus
      MATERIAL AND METHODS: it was a case control study conducted at Deptt. of
      Radiotherapy at GMCH, Chandigarh. The registers from radiology department were
      utilized and studied for the presence of history of alcohol consumption, smoking
      and tobacco intake. Statistical analysis was done by calculating Odds ratio along
      with 95% confidence interval. RESULTS: Out of 363 cases with the diagnosis of
      Laryngeal, Esophageal and Oral Cancer along with 568 controls studied, 42 (11.6%)
      were in the age group of 30-44 years, 153 (42.1%) in the age group of 45-59 years
      and rest 171 (47.1%) in the age group of 60+ years. Among cases, the percentage
      of tobacco use, smoking and alcohol consumption was 10.5, 60.6 and 33.6
      respectively as against the similar percentages among controls 1.4, 9.0 and 6.3.
      The odds ratio for tobacco use in relation to patients aged 60+ years was 2.39,
      in the age group of 45-59 years was 11.19 and increased to 55.35 in the age group
      30-44 years. Similarly the overall odds ratio for alcohol consumption was 7.48
      and it was 4.98 in the age group 60+ years, 6.30 in the age group 45-59 years and
      increasing to 17.00 in the age group of 30-44 years. CONCLUSION: Finding suggests
      that risk of cancer of the upper respiratory and alimentary tracts is higher with
      tobacco and alcohol use. Further studies are required.

PMID- 21875271
TI  - Xanthoxyletin, a coumarin induces S phase arrest and apoptosis in human gastric
      adenocarcinoma SGC-7901 cells.
AB  - This study was conducted to explore the novel anticancer compounds from Chinese
      herbs. During the process of screening, to evaluate the potential chemopreventive
      effect of natural compounds, Xanthoxyletin was isolated from Erythrina variegata.
      It has been reported that Xanthoxyletin possesses antibacterial, fungicidal, and
      algicidal properties. In this study, we examined the antiproliferative effects of
      Xanthoxyletin against SGC-7901 cells and its ability to induce apoptosis and cell
      cycle arrest for the first time. We observed that its inhibitory effects on cells
      were associated with the DNA damage, apoptosis through mitochondrial dysfunction,
      and cell cycle arrest at S phase in a dose-dependent manner. Additionally,
      Xanthoxyletin also increased the production of reactive oxygen species in SGC
      7901 cells. These results suggest that Xanthoxyletin may be promising anticancer
      agent and has worth for further mechanistic and therapeutic studies against
      gastric cancer.

PMID- 21875272
TI  - Patterns of survival for anatomical sites of colorectal cancer with shift to
      advanced lesions in Iran.
AB  - BACKGROUND: With a background of disparities in colorectal cancer (CRC)
      incidences/mortality across countries due to differences in exposure to various
      prognostic factors, this study aimed to evaluate the site-specific pattern for
      the survival of colon and rectal patients. METHODS: A total of 1,283 patients
      with CRC diagnosis according to the pathology report of cancer registry of RCGLD
      from 1 January 2002 to 1 October 2007, were entered into the study. Data were
      analyzed using univariate and multivariate competing risk survival analysis.
      RESULTS: Survival proportion of patients showed a significant trend for 1, 3 and
      5 year survival in colon cancer (P< 0.001) but this wasn't significant for rectal
      cancer (P=0.078). Tumor grade and pathologic stage were the most important
      factors predicting the survival in colon and rectal cancers with stronger hazard
      in the rectal site for grade and stronger hazard in the colon site for stage. For
      colon site, in the well and moderate categories of tumor grade, shifting from
      early to advance stage and also shifting in tumor grade from well and moderate
      categories to poor tumor grade had a considerable effect in hazard ratios. For
      rectum site, well to moderate shifting in tumor grade increased the hazard of
      death and shifting from early to advance stage increased the hazard equal to 2.54
      and 4.36 times within the well and moderate tumor differentiation, respectively.
      In shifting to advance CRC, colon site had generally worse hazard than the
      rectum. CONCLUSION: Due to the worse conditions of CRC patients as shifting to
      advance cancer, to improve the effectiveness of treatment and hence the survival
      of Iranian patients, we should pay more attention to early detection, in
      particular by implementing population based screening programmes.

PMID- 21875273
TI  - Knowledge of health effects and intentions to quit among smokeless tobacco users
      in India: findings from the International Tobacco Control Policy Evaluation (ITC)
      India Pilot Survey.
AB  - INTRODUCTION AND BACKGROUND: The prevalence of smokeless tobacco use in India is
      the highest in the world, with 26% of adults reporting being users of smokeless
      tobacco only. But to date, there are few studies of beliefs, knowledge, and other
      psychosocial measures relating to smokeless tobacco use in India. The aim of the
      present study was to use data from the ITC India Pilot Study conducted in 2006 to
      examine beliefs about the harms of smokeless tobacco use, knowledge of health
      effects, and intentions to quit among current smokeless tobacco users in two
      states, Maharashtra and Bihar. METHODS: Data from the ITC India Pilot Study, a
      face-to-face crosssectional survey of 248 adults reporting exclusive current use
      of smokeless tobacco in Maharashtra and Bihar, were analyzed with respect to the
      knowledge of health effects, beliefs about harmfulness, and intentions to quit
      smokeless tobacco use. RESULTS: Around three quarters (36%) of smokeless tobacco
      users from Maharashtra and two thirds (62%) from Bihar had a 'bad' opinion about
      smokeless tobacco use. About 77% believed that smokeless tobacco use causes mouth
      cancer, followed by gum disease (66%) and difficulty in opening the mouth (56%).
      Significant differences were found in health knowledge between urban and rural
      smokeless tobacco users in both states. Only 38% of smokeless tobacco users
      reported having intentions to quit, and only 11% had intentions to quit within
      the next 6 months. Smokeless tobacco users who reported higher knowledge of the
      specific health effects from smokeless tobacco use were more likely to have
      intentions to quit. CONCLUSION: Despite the fairly high levels of awareness of
      health effects from smokeless tobacco use in Maharashtra and Bihar, the majority
      of smokeless users had no intentions to quit. Increased educational efforts about
      the detrimental health effects from smokeless tobacco use may result in higher
      levels of knowledge about the harms of smokeless tobacco and this in turn could
      increase quit intentions and subsequent quitting among users.

PMID- 21875274
TI  - Factors influencing breast cancer screening behavior among Iranian women.
AB  - BACKGROUND: Early detection of breast cancer is of great importance to improve
      women's health and to decrease the cost related to cancer death. Therefore,
      recognition of variables related to breast cancer screening behaviors is
      necessary. Objectives of this study were to identify the rates of breast self
      examination (BSE) performance and mammography use in Iranian women, and to
      characterize the demographic and cognitive factors associated with their breast
      cancer screening behavior. METHOD: Data were collected from a convenience sample
      of 388 females, using an adapted version of Champion's revised Health Belief
      Model Scale. RESULTS: The results showed that 7.5% of the participants performed
      BSE on a regular monthly basis, and among the women aged 40 and older, 14.3%
      reported having had at least one mammography in their lifetime. Perceived self
      efficacy and perceived barriers to BSE were significant predictors for BSE
      performance. For having mammography, health motivation was the main predictor.
      CONCLUSION: Eliminating barriers and increasing perceived self-efficacy with an
      emphasis to make the women acquainted with BSE performance; as well as increasing
      health motivation of women and persuading of physicians for clinical breast
      examination (CBE) performance with low cost and free access to m ammography, are
      important to promote BSE and mammography.

PMID- 21875275
TI  - Estimating the costs of esophageal cancer screening, early diagnosis and
      treatment in three high risk areas in China.
AB  - BACKGROUND: The incidence and mortality of esophageal cancer (EC) in some rural
      areas with poor health resources in China are the highest around the world. In
      these areas, screening programs for EC are conducted for prevention and control.
      However, costs associated with esophageal cancer screening have not been
      characterized in detail. This study is aimed to estimate the screening, early
      diagnosis and treatment costs of EC using micro-costing methods, which could
      provide basic cost inputs for further systematic health economic evaluation.
      MATERIALS AND METHODS: Micro-costing methods were adopted to collect data on
      quantity and unit cost of used resources. Data was obtained from face-to-face
      interview with medical staff, local hospitals' database, and experts' input. We
      used 80% capacity utilization and 3% discount rate to annualize capital
      investments, and all costs were adjusted to year 2008 using the gross domestic
      production deflator, and then converted from Chinese currency unit to
      international dollars (I$) using purchasing power parity. RESULTS: Screening
      costs per case were around I$60. For severe dysplasia, carcinoma in situ and
      intramucosal carcinoma, the costs per capita of endoscopic mucosal resection were
      I$1292~I$1620, and around I$450 for argon plasma coagulation. For submucosal
      carcinoma (T1N0M0), and invasive carcinoma treated by esophagectomy, the
      treatment costs ranged from I$1485 to I$2171. The costs of treatment of invasive
      carcinoma were: I$497~I$685.2 for radiotherapy; I$4652~I$7966.15 for
      chemotherapy; I$1928~I$2805 for combination of esophagectomy and radiotherapy;
      I$6632~I$8082 for esophagectomy, radiotherapy and chemotherapy in combination.
      CONCLUSION: The cost analysis found screening, early diagnosis and treatment for
      EC could provide great cost savings. The results provide important information
      for further health economic evaluation, and to help the local policy makers on
      updating such screening program in high risk areas in China.

PMID- 21875276
TI  - Preoperative serum carcinoembryonic antigen, carbohydrate antigen19-9 and
      carbohydrate antigen 125 as prognostic factors for recurrence-free survival in
      colorectal cancer.
AB  - OBJECTIVE: Colorectal cancer (CRC) is among the most common malignancies
      worldwide. Understanding CRC prognosis at the initial diagnosis is very important
      for therapeutic strategy selection. This study was conducted to evaluate the
      prognostic value of preoperative serum carbohydrate antigen 19-9 (CA19-9),
      carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125) for
      predicting 5-year recurrence-free survival (RFS) in CRC patients. METHODS:
      Preoperative serum CA19-9, CEA and CA125 levels were detected by C12 protein chip
      diagnostic system in 103 patients with CRC, and their correlations with the 5
      year RFS were analyzed. RESULTS: Patients with positive preoperative serum CA19
      9, CEA and CA125 had higher 5-year recurrent rates (75.0% vs 41.0%, 65.6% vs
      39.4%, and 87.5% vs 44.2% respectively, all p< (o)0.05), and reduced median RFS
      (14 vs 35 months, 20 vs 36 months, and 4 vs 35 months respectively, all p<
      (o)0.05) compared with patients negative for corresponding tumor marker (TM). The
      median RFS was 59 months (95% CI 28.9-89.1 months) with negative TMs, 14 months
      (95% CI 4.5-23.5) for 1~2 positive TMs, and 4 months (95% CI 2.4-5.6) for all 3
      positive TMs. Patients with simultaneously positive serum CA19-9, CEA and CA125
      had the highest recurrence rate (100%) and the shortest RFS (median 4 months).
      Univariate analysis showed that stage and the preoperative single TM or combined
      TMs correlated with RFS, whereas multivariate Cox regression model analysis
      revealed only stage and preoperative serum status of CEA+CA19-9+CA125 to be
      independent prognostic factors. CONCLUSION: Preoperative serum CA19-9+CEA+CA125
      can be used an independent prognostic factor for CRC 5-year RFS.

PMID- 21875277
TI  - Impact of total and ionized serum calcium on prostate cancer risk in North Indian
      men.
AB  - INTRODUCTION: Calcium has anti-proliferative and pro-differentiation effects on
      cells in vitro and can inhibit the development of various cancers. While there is
      some epidemiologic evidence for an inverse relation between dietary calcium
      intake and prostate cancer risk, only few have focused on serum calcium levels in
      this respect. MATERIALS AND METHODS: We assayed total serum calcium and ionized
      serum calcium in a pilot study of 40 prostate cancer patients and compared with
      40 healthy controls. RESULTS: Our observations provided evidence for an
      association between prostate cancer risk and total and ionized serum calcium
      levels(p=0.020 and p<=0.001 respectively). The mean difference of total serum
      calcium was also significant in patients with serum PSA >20ng/ ml (p=0.017).
      CONCLUSION: This is an important and interesting finding which requires further
      exploration into mechanism involved in calcium channel and prostate cancer risk
      in a larger cohort of different ethnic population.

PMID- 21875278
TI  - Cancer incidence rates in the Kurdistan region/Iraq from 2007-2009.
AB  - Cancer is a disease of gradual increase in incidence overall the world. Kurdistan
      Region in Iraq has been exposed to several carcinogenic hazards. There are few
      reports about the increased risk of cancer in different cities in Iraq. These
      reports did not cover Kurdistan region. The aim of this paper was to study cancer
      incidence and to identify possible risks of cancer in this region. Cancer
      registries from 9 hospitals in three cities of Kurdistan were used as a source of
      data. Information on these cases was subjected to careful verification regarding
      repetition, place of residence and other possible errors. Overall registered
      cases in 2007, 2008 and 2009 were 1444, 2081, 2356 respectively. 49% of
      registered cases were males and 51% were female. The Age Standardized Rate of
      cancer was 89.83/100 000 among male and 83.93/100 000 among female. The results
      showed major variation in incidence rates of different types of cancer in the
      three governorates of Kurdistan. Furthermore, there was evidence of increased
      risks of cancer in Kurdistan Region in Iraq. Hematological malignancies were the
      most common cancer among male (21.13% of all cancer in males) and second most
      common in female (18.8% of all cancer in female), only exceeded by breast cancer.
      To reach sound conclusions about extent and determinants of cancer in Kurdistan,
      enormous multi-spectrum efforts are now needed.

PMID- 21875279
TI  - Linkage between prostate cancer occurrence and Y-chromosomal DYS loci in
      Malaysian subjects.
AB  - PURPOSE: Prostate cancer differs markedly in incidence across ethnic groups.
      Since this disease is influenced by complex genetics, it is many genetic factors
      may affect the level of susceptibility to development of the disease. In this
      study, four Y-linked short tandem repeats (STRs), DYS388, DYS435, DYS437, and
      DYS439, were genotyped to compare Malaysian prostate cancer patients and normal
      control males. MATERIALS AND METHODS: A total of 175 subjects comprising 84
      patients and 91 healthy individuals were recruited. Multiplex PCR was optimized
      to co-amplify DYS388, DYS435, DYS437, and DYS439 loci. All samples were genotyped
      for alleles of four DYS loci using a Genetic Analysis System. RESULTS: Of all DYS
      loci, allele 10 (A) of DYS388 had a significantly lower incidence of disease in
      compare with other alleles of this locus, while a higher incidence of disease was
      found among males who had either allele 12 (C) of DYS388 or allele 14 (E) of
      DYS439. Moreover, a total of 47 different haplotypes comprising different alleles
      of four DYS loci were found among the whole study samples, of which haplotypes
      AABC and CAAA showed a lower and higher frequency among cases than controls,
      respectively. CONCLUSIONS: It is likely that Malaysian males who belong to Y
      lineages with either allele 12 of DYS388, allele 14 of DYS439, or haplotype CAAA
      are more susceptible to develop prostate cancer, while those belonging to
      lineages with allele 10 of DYS388 or haplotype AABC are more resistant to the
      disease.

PMID- 21875281
TI  - Ultrasound operators' confidence influences diagnosis of ovarian tumors - a study
      in China.
AB  - AIM: To assess the effect of ultrasound operators' confidence in diagnosis of
      ovarian cancer, and the factors influencing diagnostic accuracy. METHODS:
      Ultrasound images of selected ovarian cancers and controls were evaluated by 8
      sinologists who were instructed to diagnose and classify lesions into benign,
      borderline or malignant, and we use structured questionnaire to investigate the
      level of confidence. We analyzed the accuracy of diagnosis, including
      sensitivity, specificity, positive and negative likelihood ratios and accuracy
      depending on the different levels of confidence. In addition, factors influencing
      diagnostic accuracy was assessed by logistic regression analysis. RESULTS: A
      total of 426 cases were examined. The confidence score was significantly
      increased with the level of accuracy (test for trend, p<0.05). Borderline tumors
      were most difficult to diagnose, and had lower accuracy, sensitivity and
      specificity compared with benign and primary invasive tumors. Working experience
      was positively closely associated with diagnosis accuracy. Logistic regression
      analysis revealed working experience and confidence score to be positively
      related to the diagnostic accuracy(OR, 95%CI, 1.68, 1.15-3.97 for working
      experience; OR, 95%CI, 3.75, 1.67-6.98 for confidence score). CONCLUSION: Our
      study showed that level of confidence is positively associated with diagnostic
      performance, and the accuracy is greatly influenced by working experience and
      confidence score.

PMID- 21875280
TI  - Beclin1 overexpression inhibitis proliferation, invasion and migration of CaSki
      cervical cancer cells.
AB  - The influence of the autophagy-related gene Beclin1 on proliferation, invasion
      and metastasis of the cervical cancer CaSki cells and its possible mechanism in
      vitro were here targeted. After the overexpression vector pcDNA3.1-Beclin1 and
      RNA interference vector pSUPER-Beclin1 were transfected into CaSki cells in
      vitro, stable expression cell lines demonstration Beclin1 expression was
      upregulated, and VEGF and MMP-9 expression were decreased, leading to cell arrest
      in the G0/G1 phase of the cell cycle. MTT assays further revealed proliferation
      of cells was significantly inhibited in Beclin1-overexpressing transfectant
      cells, with invasion and metastasis also being inhibited in Transwell chamber
      assays. The present results suggest that Beclin1 inhibits invasion and metastasis
      of cervical cancer CaSki cells in vitro. Mechanisms probably involve Beclin1
      inhibition of cell proliferation, and decreased expression of VEGF and MMP-9
      proteins.

PMID- 21875282
TI  - Gluthatione-S-transferase T1-null genotype predisposes adults to acute
      promyelocytic leukemia; a case-control study.
AB  - Polymorphisms of glutathione S-transferase (GST) proteins are correlated with
      elevated risk of many cancers including hematologic malignancies. Particularly
      concerning acute promyelocytic leukemia (APL), the studies on association between
      GSTM1, GSTT1 and GSTP1 and the disease predisposition are scarce and
      contradictory. The aim of this study was to examine whether polymorphic
      variations in GST confer susceptibility to APL. GSTM1 and GSTT1 null and GSTP1
      Ile105Val alleles were determined using polymerase chain reaction (PCR) and PCR
      RFLP, respectively, in 114 APL patients and 99 healthy controls. Frequency of
      GSTT1 null and GSTM1 null genotypes were higher in APL group which it was
      statistically significant for GSTT1 null (p< 0.01). The GSTM1 null and GSTT1 null
      conferred a 1.36-fold (OR= 1.36, 95% CI = 0.79-2.33, p= 0.18) and 2.14-fold (OR=
      2.14; 95% CI: 1.18-3.92, p= 0.013) increase in risk of APL, respectively,
      relative to the presence of the GSTM1 or GSTT1 genes. GSTP1 Ile105/Val105 and
      Val105/Val105 genotypes showed no increase in the risk of APL (OR= 0.94; 95% CI:
      0.52-1.67 and OR= 1.12; 95% CI: 0.48-2.60, respectively). Our results suggest
      that GSTT1 null genotype may be associated with increased risk of APL.

PMID- 21875283
TI  - Validation of the Turkish versions of EORTC QLQ-C30 and BR23 modules in breast
      cancer patients.
AB  - PURPOSE: To test the validity and reliability of The European Organization for
      Research and Treatment of Cancer (EORTC) core (QLQ-C30) and breast cancer module
      (QLQ-BR23) for Turkish breast cancer patients. PATIENTS AND METHODS: A total of
      127 patients treated with radiotherapy (RT) enrolled to this prospective study.
      EORTC QLQ-C30 and QLQ-BR23 modules applied to patients before initiation of RT
      and at follow-up period. Statistical analyses were performed by SPSS 13.0.
      RESULTS: Questionnaires' were found reliable and valid for Turkish breast cancer
      patients. Six of the 8 multi-item scales of QLQ-C30 had a high reliability
      (Cronbach's ? >0.7); where physical functioning and pain scores were less
      reliable (Cronbach's ? of 0.66 and 0.68 respectively). In the QLQ-BR23, 3 of 5
      multi-item scales were reliable; less reliable were breast and arm symptoms scale
      (Cronbach's ? of 0.65 and 0.61 respectively). In our analysis the most
      determinative subscales of QLQ-C30 on global health was emotional functioning
      followed by fatigue, role functioning and appetite loss (respectively p=0.002,
      p=0.01; p=0.03 and p=0.08). Among QLQ-BR23 scales systemic therapy SIDE effects,
      future perspective and upset by hair loss subscales had high impact on global
      health status (respectively p=0.006; p=0.01 and p=0.03). CONCLUSIONS: The Turkish
      version of EORTC QLQ-C30 and QLQ-BR23 modules are reliable and valid tools to
      assess quality of life of Turkish breast cancer patients.

PMID- 21875284
TI  - Role of exogenous and endogenous sources of estrogen on the incidence of breast
      fibroadenoma: case-control study in Iran.
AB  - Breast fibroadenoma (FAD) is the most common benign mammary condition among women
      but the environmental risk factors have not identified yet. As the role of long
      term estrogen exposure in the incidence of FAD has been remained controversial;
      we have decided to investigate the possible role of endogenous and exogenous
      sources of estrogens in present study. Women less than 45 years old who underwent
      surgery from June 2009 to June 2010 were matched with controls by age and
      hospital. From reproductive factors, lack of breast feeding (p< 0.001, 8.76 CI95%
      3.79-20.24), Nulliparity (p=0.001, OR=8.09, CI95% 3.505-18.67), Lack of parity
      (p=0.001, OR=6.64, CI 95% 2.56-16.31) and Hormonal dysfunction (p=0.016, OR=4.66,
      CI 95% 1.26- 17.28) were considered as the most important ones. Adiposity and
      abnormal weight gain after 18 years were considered as major background factor
      which induce FAD and may be contributed to the level of endogenous estrogen. Out
      of evaluated exogenous sources of estrogen, lower age at first OCP consumption
      (20.76_+3.87 vs. 22.85_+3.88, p=0.046) and living near Polycyclic aromatic
      hydrocarbons (PAHs) producing factories (p< 0.001, OR=3.7, CI95%1.61-7.94), were
      considered as the main sources of exposure to xenestrogens in FAD patients but
      FAD showed inverse association with cigarette smoking because of antiestrogenic
      activities of cigarette smoking . This study concludes that the incidence and
      development of FAD could be associated with the reproductive history of women,
      activity of ovarian hormones as well as environmental factors.

PMID- 21875285
TI  - Level of cancer awareness among women of low socioeconomic status in Mumbai
      slums.
AB  - BACKGROUND: Cancer, a major cause of morbidity and mortality in India can be
      prevented by early detection through screening, for which, awareness is
      essential. AIM: Determining cancer awareness among low socioeconomic women in
      Mumbai. SETTINGS AND DESIGN: Community based cancer screening study using a
      mobile van. MATERIALS AND METHODS: Data of consenting participants, collected
      using structured questionnaire, was differentiated into good and poor level of
      awareness using point based grading procedure. results: Mean age of 182
      participants, majority (90.5%) belonging to lower socioeconomic strata, was
      43.0?8.8 years. Knowledge about cancer (84.6%) was good compared to knowledge of
      cancer screening (35.1%), awareness being higher among richer and more educated.
      Major sources of information were friends or relatives (46.1%) and media (35.2%).
      Only 6.6% had undergone prior screening. CONCLUSION: In spite of appreciable
      knowledge about cancer, creating awareness about screening, its availability, and
      motivating the general population for screening is necessary.

PMID- 21875286
TI  - Anticlastogenic and anticarcinogenic potential of Thai bitter gourd fruits.
AB  - Thai bitter gourd fruits (Momordica charantia Linn., TBG) has been previously
      demonstrated to possess phase II detoxificating enzymes inducing properties, as
      well as the ability to reduce phase I carcinogen activating enzyme activity in
      rat liver. In addition, it was partially inhibited 7,12-dimethylbenz(a)anthracene
      (DMBA)- induced mammary gland carcinogenesis in female Sprague-Dawley rats. In
      this study, we therefore examined the anticlastogenic and anticarcinogenic effect
      of TBG against clastogens, cyclophosphamide (CYP) and DMBA, in mice using the in
      vivo erythrocyte micronucleus assay and azoxymethane (AOM)-induced colon
      carcinogenesis in rats, respectively. For anticlastogenicity test, male mice were
      fed with modified AIN-76 diets containing 6.25% and 12.5% of ground freeze-dried
      TBG for 2 weeks prior to administration of clastogens till the end of experiment.
      Blood samples were collected and counted for reticulocytes by using the
      fluorescent microscope. For anticarcinogeicity test, male Wistar rats were fed
      with modified AIN-76 diets containing 5% and 10% ground freeze-dried TBG for 2
      weeks prior to, during and 1 week after the completion of AOM administration (15
      mg/kg once a week for 2 weeks). It was found that TBG at 6.25% resulted in a
      significant reduction in micronucleated peripheral reticulocytes (MNRETs) induced
      by only CYP. Study on anticarcinogenic potential demonstrated that rats fed with
      TBG diets at the concentration tested developed significantly higher incidence as
      well as the multiplicities of colon tumors than the control group. These results
      demonstrated that Thai bitter gourd fruits possesses anticlastogenic potential
      against clastogen in the mouse. Interestingly, it had no preventive potential
      against AOM-induced colon carcinogenesis in rat, rather increasing the incidence
      of colonic neoplasm when giving during the initiation stage.

PMID- 21875287
TI  - MiR-138 suppresses expression of hypoxia-inducible factor 1alpha (HIF-1alpha) in
      clear cell renal cell carcinoma 786-O cells.
AB  - OBJECTIVES: Hypoxia-inducible factor-1alpha (HIF-1a) is widely considered to be
      one of the key regulators in cancer cells. Here, we investigated a microRNA
      regulating expression of HIF-1a and explored its functions in clear cell renal
      cell carcinoma (ccRCC) cells. METHODS AND MATERIALS: Western blot and reporter
      assays were used to assess HIF-1a as a direct target of miR-138. The effects of
      miR-138 or si-HIF-1a on ccRCC 786-O cells were also estimated by apoptosis
      analysis and cell migration assay. RESULTS: The data showed HIF-1a to be one
      target of miR-138. Futhermore, inhibition of the expression of HIF-1a with
      specific siRNA or miR-138 could increase apoptosis and reduce the migration of
      786-O cells. CONCLUSIONS: miR-138 could inhibit the expression of HIF-1a and
      regulate the apoptosis and migration of ccRCC cells.

PMID- 21875288
TI  - Smoking prevalence and associated attitudes among high school students in Turkey.
AB  - This is a descriptive study to determine the smoking prevalence and attitudes
      with smoking among high school students in Sivas, Turkey. This study was carried
      out in 6 high schools located in Sivas, Turkey. The sample was constituted by
      1050 students. The data of the study was obtained by a questionnaire which is
      developed by researchers. The x2 test was used in the statistical analyses. In
      this study, the rate of students who did not smoke or stopped smoking was found
      to be 79.6%, while the rate of occasionaly or daily smokers was 20.4%. Students
      with male gender, those whose fathers and mothers had a low educational level,
      and a smoking mother, father or sibling, had a higher frequency of smoking (p<
      0.05). Students were found to have opposite attitudes to cigarette in general and
      rates of agreed to some attitude expressions were found to be higher in non
      smoking students. The results demonstrated that the smoking prevalence among high
      school students was high and students with a smoking family member in particular,
      those with parents having low educational levels and of male gender should be
      regarded as a risk group for smoking.

PMID- 21875289
TI  - Antimutagenicity and antioxidative DNA damage properties of oligomeric
      proanthocyanidins from Thai grape seeds in TK6 cells.
AB  - Oligomeric proanthocyanidins (OPCs) are found mostly in red grape seeds. Many
      publications have reported that OPCs possess an excellent anti-oxidant effects.
      Since it could against cellular damage from reactive oxygen species (ROS) led to
      reduce the risk of chronic disease and cancers. We carried out this study on the
      Thai OPCs to evaluate the mutagenicity/ anti-mutagenicity and anti-oxidative DNA
      damage effects in TK6 cells by micronucleus (MN) and comet assays. In the MN
      assay, OPCs-treatment of TK6 cells at concentrations ranging from 10-200 ?g/ml (4
      and 24 h) did not cause micronucleus induction over the negative control group
      but revealed a significant reduction the micronucleus frequencies against the
      known mutagen (mitomycin C). In the comet assay, OPCs-treated TK6 cells at
      concentrations of 100, 250, 500, and 1,000 ?g/ml could inhibit DNA damage induced
      by H(2)O(2) as indicated by 18.7, 36.4, 30.6, and 60.1%, respectively. Our
      results suggest that OPCs possess the anti-mutagenic and anti-oxidative DNA
      damage effects in TK6 cells under the conditions of this assay.

PMID- 21875290
TI  - Epidemiologic status of bladder cancer in Shiraz, southern Iran.
AB  - BACKGROUND: Bladder cancer is the second most common malignancy of the
      genitourinary tract worldwide after prostate cancer. However, in Iran it is the
      most common cancer of the genitourinary system and the third most common cancer
      in males. The increasing trend in bladder cancer incidence in recent decades,
      along with the lack of research on this malignancy in Iran, make epidemiologic
      research important in light of its preventability through early recognition and
      limiting exposure to risk factors. The present study aimed to assess the
      epidemiology of bladder cancer in Shiraz, a large city in southern Iran, during a
      2-year period. METHODS: The data for this study were obtained from the population
      based cancer registry of the Vice-Chancellery for Health Affairs of Shiraz
      University of Medical Sciences and Shiraz hospitals between March 1, 2007 and
      March 1, 2009. Demographic, clinical and pathological aspects of 216 patients
      with bladder cancer were investigated through careful review of their medical
      records. Statistical analyses were performed with SPSS software. P values less
      than 0.05 were considered statistically significant. RESULTS: We analyzed data
      for 179 (82.9%) men and 37 (17.1%) women (mean age of 65.1?12.7 years). Tobacco
      and opium use were found in 109 (65.3%) and 44 (34.1%) patients, respectively.
      Cigarette smokers and water pipe smokers were mostly men (P=0.001 and P=0.04,
      respectively). The most common type of tumor was transitional cell carcinoma
      (95.7%) and most tumors were of low malignant potential grade (39.7%). Nearly
      half of the patients suffered recurrence. CONCLUSION: Comparisons with previous
      studies showed that bladder cancer tends to appear slightly more often in the
      elderly and that the tumors tend to have a higher grade of malignancy in our
      region. There is a need for more epidemiologic studies on the trends in the
      incidence and other epidemiologic indices.

PMID- 21875291
TI  - Intellectual and behavioral impairment after chemotherapy and radiotherapy among
      children with cancer in Iran.
AB  - OBJECTIVE: It is well established that treatment modalities against cancer have
      psychosocial and serious medical side effects especially neurologic, learning,
      and intellectual disorders among children with cancer. The aim of this study was
      to evaluate the behavioral change specially the effect of chemotherapy and
      cranial radiotherapy on the development of attention deficit hyperactivity
      disorder (ADHD) in children with cancer. MATERIALS AND METHODS: The children
      diagnosed with cancer and referred to Mahak Hospital (a well funded charity
      organization helping children with cancer in Iran) participated in this study. To
      assess the post treatment behavior, the Conner's Rating Scales (CRS)
      questionnaire, which its reliability and validity has been well established was
      administrated by trained interviewer in a two hour sessions to mother or
      attending nurses of the cases. The relationship between attention deficits,
      hyperactivity disorder were assessed with different categories of treatment,
      socio-economic status, age at diagnosis, sex, as well as duration since
      treatment. RESULTS: During periods of six months, 30 subjects (16 male and 14
      female) were studied and participated in the study. Fifteen cases had both
      radiotherapy as well as chemotherapy and 15 cases just had chemotherapy as their
      treatment regiment. The mean Conner's Rating Score (total score of ADHD) were
      higher among those who received both chemotherapy and radiotherapy compared with
      those who had just chemotherapy but it was not statistically significant
      (34.7?12.6 for just chemotherapy and 39.3?9.0 for chemo and radiotherapy
      together). The total Conner's Rating Score was higher among girls compared to
      boys (mean ? standard deviation was 39.8?9.4 for girls and 33.7?12 for boys).
      Duration since treatment, age diagnosis, and mother's level of education had
      effect in post treatment intellectual capacity and behavioral aspect of patients.
      CONCLUSION: In the light of dramatic improvement of survival among children with
      cancer the intellectual and behavioral impairment due to treatment modalities
      needs serious attention and proper medical management.

PMID- 21875292
TI  - Helicobacter pylori and oral cancer: possible association in a preliminary case
      control study.
AB  - Oral cancer is the most common cancer diagnosed in Indian men and is the leading
      cause of cancer deaths. Helicobacter pylori have been reported to be present in 0
      40% of the cases with head neck cancer. A higher percentage has been identified
      in laryngeal and pharangeal cancer. We here carried out a hospital-based, case-
      control study of 20 patients with newly diagnosed oral cancer and 20 healthy
      controls without any cancer to evaluate associations between H pylori infection
      and oral cancer using culture and 16sRNA PCR technique for bacterial
      identification. H pylori was isolated from the culture of three cases and one
      control, while three cases and two control showed PCR positivity for H Pylori
      16sRNA. The odds ratio by culture was 3.0, 95% CI 0.34- 26.4 and 1.5, 95% CI 0.28
      8.03 by PCR. None of the observed odds ratio was statistically significant.
      However, the results of this pilot study suggest a possible association of H.
      pylori with an increased risk of oral cancer. Additional studies in larger
      populations are necessary to confirm and to quantify this possible association
      more accurately.

PMID- 21875293
TI  - Situation analysis of risk factors related to non-communicable diseases in Khon
      Kaen Province, Thailand.
AB  - A descriptive cross-sectional study was carried out in Khon Kaen Province during
      January 1 to June 30, 2008. The aims were to assess: (1) the prevalence of risk
      factors for chronic diseases such as cancer, diabetes, blood pressure; and (2)
      health behaviour and health education needs. There were 338 sample subjects aged
      between 20-60 years, from urban, semi-urban and rural areas. Some 20.4 % of the
      sample subjects reported that they were unhealthy (10.4% diagnosed with
      hypertension, 9.8% with diabetes, and 0.9% with cancer). For history of illness
      in the family, the most common were diabetes (42%), high blood pressure (16.5 %)
      and cancer (14.8 %), and 66.9% reported stress within the last 6 months. In terms
      of risk behavior, 82.3% of males smoked cigarettes but only 1.9% of females. The
      respective figures for alcohol were 68.4% and 26.6%. The majority (61.2) had low
      physical activity (sitting or standing, little movement). Almost one third (32%)
      reported testing positive for Opisthorchis viverrini eggs in stool. For health
      education needs, 64.2%, 54.7% and 42.6% wanted to learn more about cancer,
      diabetes and hypertension, respectively. For means of health education delivery,
      31.7% want to learn from medical doctors, 20.4% from TV, 16.3% from village's
      broadcasting and 13.6% from health volunteers. Suitable means to delivery health
      education are needed to convey knowledge to the population. Community health
      volunteers may be one of the best sustainable alternative methods to transfer
      knowledge.

PMID- 21875294
TI  - MTHFR polymorphisms and Opisthorchis viverrini infection: a relationship with
      increased susceptibility to cholangiocarcinoma in Thailand.
AB  - Opisthorchis viverrini (OV) infection is the major risk factor for
      cholangiocarcinoma (CCA). Methylenetetrahydrofolate reductase (MTHFR) is an
      important enzyme in folate metabolism. Change in MTHFR activity may influence
      both DNA methylation and synthesis, crucial steps in carcinogenesis. This study
      aimed to investigate the association between MTHFR polymorphisms and OV infection
      with CCA risk in a high-incidence area of Thailand. A nested case-control study
      within cohort study was carried out: 219 subjects with primary CCA were matched
      with two non-cancer controls from the same cohort on sex, age at recruitment and
      presence/ absence of OV eggs in stool. At the time of recruitment information on
      consumption of foodstuffs potentially contaminated by OV was obtained by
      questionnaire. MTHFR polymorphisms were analyzed using PCR with high resolution
      melting analysis. Associations between variables and the risk of CCA were
      assessed using conditional logistic regression. Risk of CCA was related to
      consumption of a dish of raw freshwater fish (Koi- Pla) with clear dose-response
      effects, and there were joint effects on CCA risk between MTHFR polymorphisms and
      consumption of dishes containing raw- and/or semi-raw freshwater fish. This study
      provides evidence to support a relationship of increased susceptibility to CCA in
      individuals with MTHFR variants, especially for those individuals who have OV
      infection or consume semi-raw freshwater fish (acting either as a source of OV or
      of pre-formed nitrosamine). Folate may play an important role in OV-related
      cholangiocarcinogenesis by upsetting the balance between DNA methylation and
      synthesis in the folate pathway.

PMID- 21875295
TI  - Factors related to poor practice of Pap smear screening among secondary school
      teachers in Malaysia.
AB  - INTRODUCTION: The Pap smear test has been regarded as a promising cervical
      screening tool since 1940s. Yet its importance has been overlooked by
      beneficiaries in Malaysia. This underlines the need to identify the prevalence of
      Pap smear practice and influencing factors towards the practice among educated
      working women. METHODS: A survey was conducted with 403 female teachers from 40
      public secondary schools in Malaysia selected by cluster random sampling. Data
      were collected from January to March 2010 using a self-administered
      questionnaire. Multivariate logistic regression was performed to identify the
      factors related to the Pap smear practice. RESULTS: The rate for participants who
      ever had Pap test was only 38% and poor practice of was significantly higher
      among: those with aged less than 35 years; those practicing hormonal
      contraceptive method; and individuals perceiving barriers to the Pap smear
      screening test. In contrast, the findings were significantly lower in women with
      longer duration of teaching service; higher income groups; ever pregnant; having
      chronic diseases; health insurance coverage; and who had perceived benefit of Pap
      smear screening. CONCLUSION: Barriers towards practicing Pap smear exist even
      among educated career women. Tailor-made health promotion and education on
      cervical cancer and the benefit of Pap smear screening are essential to change
      the behavior of the study population.

PMID- 21875296
TI  - Determining nurse-midwives' knowledge of the Pap-smear test and their rate of
      being tested in Turkey.
AB  - BACKGROUND: Cervical cancer is one of the most common causes of cancer mortality
      among women worldwide, but actually is largely preventable. The practice of Pap
      smear testing (PST) needs to be expanded in order to diagnose cervical cancer at
      an early stage and thus reduce the burden this women's health problem brings to
      the society. Effective public education is therefore crucial. Determining the
      knowledge and practice of nurses in this field will help plan their training and
      develop the necessary training program with an adequate content. This descriptive
      study aimed at determining the knowledge on, and status of the PST among the
      nurse/midwives. METHODS: The subjects comprised nurse/midwives working in the
      gynecologic/obstetric clinics of three big hospitals located in the central city
      of Ankara. The data collected through questionnaire were evaluated by means of
      the package software SPSS as well as decimal number and Chi-square tests.
      RESULTS: The results revealed that the nurse/midwives had not enough knowledge on
      PST, of whom 58.1% had got no PST, while a portion of 71.5% of those who had
      already underwent a PST failed in getting regular tests, and a portion of 73.5%
      had got no on-job training on the gynecological cancers, and a portion of 66.7%
      of the trained ones had not any knowledge in respect of PTS. It was determined
      that there was a significant statistical difference in the level of knowledge on
      PST in terms of on-job training in respect of the gynecological cancers and the
      PST history (p<0.05).

PMID- 21875297
TI  - Apoptosis of human ovarian cancer cells induced by Paris chinensis dioscin via a
      Ca(2+)-mediated mitochondrion pathway.
AB  - BACKGROUND: Study of the mechanisms of apoptosis in tumor cells is an important
      field of tumor therapy and cancer molecular biology. Apoptosis triggered by
      activation of the mitochondrial-dependent caspase pathway represents the main
      programmed cell death mechanism. The mitochondrial-dependent apoptosis pathway is
      activated by various intracellular stresses that induce permeabilization of the
      mitochondrial membrane, leading to cytochrome C release. This study was to
      investigate the anti-tumor effects of Dioscin from traditional Chinese anti-snake
      venom medicine Paris chinensis (PCD) and correlated mechanisms regarding
      apoptosis in human ovarian cancer SKOV3 cells. METHODS: Cell viability was
      analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyl-tetrazolium bromide
      (MTT) assay. Cell apoptosis was evaluated by flow cytometry and Laser Scanning
      Confocal Microscope (LSCM) using Annexin-V/PI staining. Intracellular calcium
      ions were detected using fluorescence microscopy. The expression of apoptosis
      related proteins cytochrome C and caspase-3 was measured by immunohistochemical
      staining. RESULTS: PCD had an anti-proliferation effect on human ovarian cancer
      SKOV3 cells in a dose- and time-dependent manner. After treatment with PCD, the
      apoptotic rate significantly increased, and accompanied with the increased levels
      of caspase-3 and cytochrome C protein in SKOV3 cells. Morphological changes
      typical of apoptosis were also observed with LSCM by Annexin V/PI staining.
      Moreover, intracellular calcium accumulation occurred in PCD-treated cells.
      CONCLUSIONS: The molecular determinants of inhibition of cell proliferation as
      well as apoptosis of PCD may be associated with the activation of Ca2+-related m
      itochondrion pathway in SKOV3 cells.

PMID- 21875298
TI  - Liver fluke prevention and control in the northeast of Thailand through action
      research.
AB  - The aim of this action research was to enhance people's potential to prevent and
      control liver fluke infestation. The subjects were a total of 96 participants
      comprising 20 community leaders, 74 individuals handling and preparing food, and
      2 officials from the Local Administration. Quantitative data were collected
      through questionnaire and the results of stool examination of the participants
      were recorded. The main methods used to collect qualitative data were focus group
      discussions and in-depth interviews. For qualitative data analysis, the
      researchers undertook a qualitative content analysis. For quantitative data,
      conventional descriptive statistics were used and the mean differences with the
      95% CI before and after the study were compared. The results in the early stage
      found that the participants were not aware of the fact that eating raw fish might
      be the cause of developing cholangiocarcinoma. 94.8% of participants however knew
      that eating raw fish might be cause having liver fluke infection which can be
      treated be taking an antihelminthic drug. They perceived that it is way of life
      since their ancestors already consumed raw fish because they found it to be
      delicious. However, through participating in this study, it was realized how
      dangerous it is to get infected with the liver fluke. Participants also learned
      the life cycle of liver fluke. They talked about this within their families, and
      communicated as well as cooperated with others to strengthen a network of a club
      concentrating on not eating raw fish. The communities and the Sub-district
      Administrative Organization supported the project. In conclusion, it is advisable
      to improve the behavior of participants in villages so that they became aware how
      to prevent and control liver fluke infection and therefore the development of
      cholangiocarcinoma.

PMID- 21875299
TI  - Where do women give birth in rural Tanzania?
AB  - INTRODUCTION: Skilled birth attendance is one of the key factors in improving
      maternal and neonatal health but coverage is frequently less than 50% in many
      African and Asian countries, especially in rural areas. This article reports the
      findings on skilled birth attendance in a remote area with a large nomadic
      population in northern Tanzania. METHODS: In a secondary analysis of data from a
      retrospective study on immunisation rates, data were compiled on the rates of
      skilled birth attendance at 8 mobile reproductive and child health clinics run by
      a rural first-referral hospital in the Mbulu area, covering the years 1998, 1999,
      2006 and 2007. These data were analysed according to tribal affiliation and
      distance from health institutions with obstetric services. RESULTS: Based on 3851
      data sets, average rates of skilled birth attendance were 27%, 24%, 28% and 30%
      in 1998, 1999, 2006 and 2007, respectively (p = 0.02). At individual clinics,
      rates could be as low as 5-10%. Only at one clinic, significant improvement
      occurred over time (p< 0.01). In the univariate analysis, affiliation to the
      Iraqw tribe was a strong predictor of higher rates of skilled birth attendance in
      comparison with the nomadic Datoga tribe for all years combined (odds ratio [OR]
      2.43 [95% confidence interval {CI} 1.92-3.07]), whereas distance showed only a
      minor influence (OR 1.02 [95% CI 1.01-1.02]). In the multivariate analysis, only
      tribal affiliation in 2007 (OR 2.69 [95% CI 1.12-6.46]) and for all years
      combined (OR 1.65 [95% CI 1.04-2.61]) was a significant factor. CONCLUSIONS: This
      study documented lower than the national average rates of skilled birth
      attendance in a rural area in Tanzania, especially among the nomadic Datoga
      tribe, over several years. The effect of distance was not consistent. To increase
      rates of women giving birth with skilled attendance in rural, remote settings and
      in populations with large proportions of nomadic people, a multi-facetted
      approach involving education in and sensitisation for pregnancy- and delivery
      related issues, support for planned and emergency transportation, and improved
      quality of obstetric and neonatal services needs to be explored.

PMID- 21875300
TI  - Stress, glucocorticoids and liquorice in human pregnancy: programmers of the
      offspring brain.
AB  - A suboptimal prenatal environment may induce permanent changes in cells, organs
      and physiology that alter social, emotional and cognitive functioning, and
      increase the risk of cardiometabolic and mental disorders in subsequent life
      ("developmental programming"). Although animal studies have provided a wealth of
      data on programming and its mechanisms, including on the role of stress and its
      glucocorticoid mediators, empirical evidence of these mechanisms in humans is
      still scanty. We review the existing human evidence on the effects of prenatal
      maternal stress, anxiety and depression, glucocorticoids and intake of liquorice
      (which inhibits the placental barrier to maternal glucocorticoids) on offspring
      developmental outcomes including, for instance, alterations in
      psychophysiological and neurocognitive functioning and mental health. This work
      lays the foundations for biomarker discovery and affords opportunities for
      prevention and interventions to ameliorate adverse outcomes in humans.

PMID- 21875301
TI  - Chronic stress-induced alterations in mouse colonic 5-HT and defecation responses
      are strain dependent.
AB  - Mood disorders and chronic stress are frequently associated with gastrointestinal
      (GI) symptoms including diarrhoea or constipation. Locally produced serotonin [5
      hydroxytryptamine (5-HT)] regulates GI motility and is a key factor in the
      pathophysiology of stress-associated GI disorders. We aimed to establish whether
      chronic stress can differentially affect faecal output and colon 5-HT
      concentration in two inbred mouse strains: BALB/c and C57BL/6 which differ in
      their ability to cope with stress. Adult male BALB/c and C57BL/6 mice were
      restrained for 2 h daily for 10 days. Defecation was monitored during each stress
      session. Twenty-four hours after the last session of stress, plasma
      corticosterone concentration was higher than control in both strains, indicative
      of a physiological effect of chronic stress; however, stress-induced diarrhoea
      was more persistent in C57BL/6 mice. Basal concentration of colon 5-HT was higher
      in C57BL/6 mice, and stress elicited an increase in colon 5-HT only in this
      strain. Finally, naive BALB/c mice had a higher sensitivity (incidence of
      diarrhoea) to 5-HT (0.33 mg/kg, i.p.) than C57BL/6 mice. Our results suggest that
      differential defecation responses to stress may be associated with colon 5-HT
      concentration, which may in turn reflect the individual sensitivity to 5-HT. In
      addition, C57BL/6 mice emerge as a relevant model for studying GI alterations
      induced by chronic stress.

PMID- 21875302
TI  - Behavioral and physiological responses of young horses to different weaning
      protocols: a pilot study.
AB  - In this study, effects of weaning on behavioral and physiological stress
      parameters in young horses (foals) were determined. Foals were weaned either
      simultaneously without the presence of adult horses (group A, n = 6), or in the
      presence of two adult females familiar but unrelated to the foals (group B, n =
      5), or weaned consecutively by removing two mother horses per day (group C, n =
      6). Behavior, locomotion, salivary cortisol concentration, beat-to-beat (RR)
      interval, heart rate variability (HRV) and weight were determined. Group A foals
      lost weight for 2 days (mean +/- SEM) - 8.3 +/- 1.6 kg, p < 0.05. Weaning was
      followed by increased vocalization which was least pronounced in foals of group B
      (p < 0.05). Locomotion was most pronounced on weaning day in foals of group A and
      lowest in group B (p < 0.05). Weaning increased salivary cortisol concentration
      on the day of weaning in groups A and B and for 2 days in group C (p < 0.05). The
      RR interval decreased most pronouncedly in group A foals (p < 0.05). There were
      no consistent changes in HRV. Based on cortisol release and behavior, weaning is
      associated with stress but this was least pronounced in foals weaned in the
      presence of two familiar but unrelated adult female horses.

PMID- 21875303
TI  - Self-reported psychological stress and the risk of breast cancer: a case-control
      study.
AB  - The aim of this study was to examine the relationship between severe life events
      and breast cancer risk. This study was based on a case-control examination of 858
      Polish invasive breast cancer cases and 1085 controls matched for age and place
      of residence. Data on life events, sociodemographic characteristic, reproductive
      factors, family history of breast cancer, current weight and height, and
      lifestyle habits were collected between January 2003 and May 2007 using a self
      administered questionnaire. Odds ratios with 95% confidence intervals were
      estimated as the measure of the relationship between life event stress and breast
      cancer risk using unconditional logistic regression analyses. After adjustment
      for potential breast cancer risk factors, women with four to six individual major
      life events had 5.33 times higher risk for breast cancer, compared with those in
      the lowest quartile. Similarly, women with a lifetime life change score greater
      than 210 had about 5 times higher risk compared to women with corresponding
      scores in the range 0-70. Several life events (death of a close family member,
      personal injury or illness, imprisonment/trouble with the law, retirement) were
      significantly associated with breast cancer risk. These findings suggest that
      major life events can play an important role in the etiology of breast cancer.

PMID- 21875304
TI  - Dopamine D1 receptors are responsible for stress-induced emotional memory deficit
      in mice.
AB  - It is established that stress impairs spatial learning and memory via the
      hypothalamus-pituitary-adrenal axis response. Dopamine D1 receptors were also
      shown to be responsible for a stress-induced deficit of working memory. However,
      whether stress affects the subsequent emotional learning and memory is not
      elucidated yet. Here, we employed the well-established one-trial step-through
      task to study the effect of an acute psychological stress (induced by tail
      hanging for 5, 10, or 20 min) on emotional learning and memory, and the possible
      mechanisms as well. We demonstrated that tail hanging induced an obvious stress
      response. Either an acute tail-hanging stress or a single dose of
      intraperitoneally injected dopamine D1 receptor antagonist (SCH23390)
      significantly decreased the step-through latency in the one-trial step-through
      task. However, SCH23390 prevented the acute tail-hanging stress-induced decrease
      in the step-through latency. In addition, the effects of tail-hanging stress
      and/or SCH23390 on the changes in step-through latency were not through non
      memory factors such as nociceptive perception and motor function. Our data
      indicate that the hyperactivation of dopamine D1 receptors mediated the stress
      induced deficit of emotional learning and memory. This study may have clinical
      significance given that psychological stress is considered to play a role in
      susceptibility to some mental diseases such as depression and post-traumatic
      stress disorder.

PMID- 21875306
TI  - Preventing youth violence perpetration among girls.
AB  - In the last 10 years, several reviews of research on violence among girls have
      been conducted. This research helps to determine the extent of girls' use of
      violence however, it has not been translated into effective prevention programs
      for girls. This article reviews the research on risk and protective factors
      associated with violence, with particular attention on factors unique to girls or
      shared between boys and girls. Individual risk factors for youth violence include
      hyperactivity/inattention/impulsivity, risk taking/sensation seeking, low
      academic achievement, exposure to stress and victimization, and early puberty.
      Parent-child relationships/parental monitoring and supervision, parent criminal
      and antisocial behavior, and family conflicts and instability have been found to
      be relationship-level risk factors. Peer risk factors include deviant peer
      affiliation and gang membership. Risk factors at the community level include
      economic deprivation; community disorganization; the availability of drugs,
      alcohol, and firearms; and neighborhood crime. This review also includes a
      description of program effects for girls within the Model and Promising
      Blueprints for Violence Prevention Initiative programs. Very few evaluations have
      examined program effectiveness in preventing violence among girls. More
      evaluation research is needed to determine if evidence-based programs have
      positive impact on reducing violence and related risk factors among girls.

PMID- 21875305
TI  - Effects of chronic social stress during lactation on maternal behavior and growth
      in rats.
AB  - Maternal mood disorders such as depression and chronic anxiety can negatively
      affect the lives of not only mothers, but also of partners, offspring, and future
      generations. Chronic exposure to psychosocial stress is common in postpartum
      mothers, and one of the strongest predictors of postpartum depression is social
      conflict. The objective of the current study was to evaluate the effects of
      chronic social stress (CSS) during lactation on the maternal behavior (which
      consists of maternal care and aggression toward a novel conspecific) of lactating
      rats, as well as on the growth of the dams and their offspring. It was
      hypothesized that chronic daily exposure to a novel male intruder would alter the
      display of maternal behavior and impair growth in both the dam and offspring
      during lactation due to the potentially disruptive effects on maternal behavior
      and/or lactation. The data indicate that CSS during lactation attenuates maternal
      care and the growth of both dams and pups, and increases self-grooming and
      maternal aggression toward a novel male intruder. These results support the use
      of CSS as a relevant model for disorders that impair maternal behavior and
      attenuate growth of the offspring, such as postpartum depression and anxiety.

PMID- 21875307
TI  - The nature and correlates of avoidance in obsessive-compulsive disorder.
AB  - OBJECTIVES: Avoidance in obsessive-compulsive disorder (OCD) has been neglected
      by research. This study aimed (i) to collect information on the nature and
      frequency of avoidance in people with OCD and ascertain the types of obsessions
      related to avoidance; (ii) compare OCD individuals with and without avoidance,
      and (iii) determine predictors of avoidance in people with OCD. METHOD: A total
      of 124 OCD adults underwent a comprehensive assessment. Participants were asked
      whether they engaged in any avoidance behaviour because of their OCD, and the
      nature and number of instances of such avoidance were recorded. The instances of
      avoidance were grouped according to the type of obsession and compulsion that
      they were related to. RESULTS: A total of 74 (59.7%) participants reported OCD
      related avoidance. Avoidance was most commonly related to contamination
      obsessions. Almost 80% of all contamination obsessions and more than 50% of all
      aggressive obsessions were associated with avoidance, and contamination
      obsessions were significantly more common among the participants with avoidance.
      In contrast, very few obsessions about a need to collect and keep objects and
      obsessions about a need for ordering, arranging and doing things right or in an
      exact way were associated with avoidance; these types of obsessions were also
      significantly more common among the participants without avoidance. The strongest
      predictor of avoidance was the presence of contamination obsessions. Participants
      with avoidance had a significantly more severe OCD than those without avoidance.
      CONCLUSIONS: Avoidance is common in OCD, and it is particularly frequently
      associated with contamination obsessions. There is a weak link between avoidance
      and hoarding and between avoidance and ordering/arranging/symmetry obsessions and
      compulsions. These results, along with the finding that OCD with avoidance is a
      more severe illness, have implications for the future diagnostic criteria,
      description, subtyping and treatment of OCD and for its relationship with other
      anxiety disorders.

PMID- 21875308
TI  - Catatonia associated with temazepam withdrawal.

PMID- 21875309
TI  - Estimating the prevalence of DSM-IV mental illness in the Australian general
      population using the Kessler Psychological Distress Scale.
AB  - OBJECTIVE: The aim of this study was to present scoring rules for predicting DSM
      IV mental illness in the previous 12 months using the Kessler Psychological
      Distress Scale in the Australian population. METHOD: The method described in
      Kessler et al. was closely followed using data from the 2007 Australian Survey of
      Mental Health and Wellbeing. A series of 93 nested logistic regression models
      were generated and compared to estimate the predicted probabilities of mental
      illness for each survey respondent using scores on the Kessler Psychological
      Distress Scale. The best model was selected using information theoretic criteria.
      Concordance between the predicted probabilities of mental illness generated by
      the best models with DSM-IV defined mental illness, assessed using the Composite
      International Diagnostic Interview, was determined using receiver operating
      characteristic analysis. RESULTS: The best fitting models were found to contain
      the quadratic form of the Kessler Psychological Distress Scale (both 6 item and
      10 item versions). Age was found to be significant in the model predicting mood,
      anxiety, and substance use with serious impairment using the 6 item version
      whilst age and gender was found to be significant in the model for the 10 item
      version. The concordance between the predicted probabilities of mood, anxiety,
      and substance use with serious impairment generated from the best models and DSM
      IV mood, anxiety, and substance use with serious impairment was within an
      acceptable level for both versions. Results were similar when predicting DSM-IV
      mood, anxiety, and substance use without seriousness indicators and DSM-IV
      anxiety and depression. The performance of predicted probabilities was then
      examined in various sub-populations of the Australian population. CONCLUSIONS:
      Using a logistic regression model, the Kessler Psychological Distress Scale can
      be used to generate predicted probabilities of mental illness with an acceptable
      level of agreement in Australian-based population studies where it is not
      feasible to conduct a comprehensive assessment.

PMID- 21875310
TI  - Non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) refers to the accumulation of hepatic
      steatosis not due to excess alcohol consumption. The prevalence of NAFLD is up to
      30% in developed countries and nearly 10% in developing nations, making NAFLD the
      most common liver condition in the world. The pathogenesis of NAFLD is related to
      insulin resistance and, thus, it is frequently found in individuals who have
      central obesity or diabetes. Insulin resistance and excess adiposity are
      associated with increased lipid influx into the liver and increased de novo
      hepatic lipogenesis, promoting hepatic triglyceride accumulation. Defects in
      lipid utilization via mitochondrial oxidation and lipid export may also
      contribute to hepatic lipid build-up. Adipocytokine alterations, lipotoxicity
      from saturated fatty acids and fructose have been all been implicated in causing
      hepatocyte injury in NAFLD through pathways involving oxidative and endoplasmic
      reticulum stress. Clinically, NAFLD is commonly asymptomatic and frequently
      detected incidentally by blood liver function tests or imaging performed for
      other reasons. Subjects with NAFLD have a higher mortality rate than the general
      population and are at increased risk of developing cardiovascular disease and
      diabetes in the future. Histologically, NAFLD occurs as a spectrum from mild
      hepatic steatosis only, to non-alcoholic steatohepatitis (NASH) characterized by
      hepatocellular injury and inflammation, to cirrhosis. A diagnosis of NASH with
      associated fibrosis heralds a more significant prognosis as it is more likely to
      progressive to cirrhosis with complications of hepatic failure and hepatocellular
      carcinoma. Currently, the diagnosis of NASH requires a liver biopsy, however,
      serum based markers of hepatocyte apoptosis such as cytokeratin-18 fragments
      offer promise as accurate non-invasive diagnostic tests. Treatment of NAFLD
      revolves around addressing concomitant metabolic risk factors and improving
      insulin resistance through weight loss measures and exercise. Insulin sensitizing
      agents such as pioglitazone and anti-oxidant agents such as vitamin E show some
      promise in improving liver histology in patients with NASH, however, the long
      term benefit of these medications has not been demonstrated.

PMID- 21875311
TI  - Free radicals and antioxidants at a glance using EPR spectroscopy.
AB  - The delicate balance between the advantageous and detrimental effects of free
      radicals is one of the important aspects of human (patho)physiology. The
      controlled production of reactive oxygen and nitrogen species has an essential
      role in the regulation of various signaling switches. On the other hand,
      imbalanced generation of radicals is highly correlated with the pathogenesis of
      many diseases which require the application of selected antioxidants to regain
      the homeostasis. In the era of growing interest for redox processes, electron
      paramagnetic resonance (EPR) spectroscopy is arguably the best-suited technique
      for such research due to its ability to provide a unique insight into the world
      of free radicals and antioxidants. Herein, I present the principles of EPR
      spectroscopy and the applications of this method in assessing: (i) the oxidative
      status of biological systems, using endogenous long-lived free radicals (ascorbyl
      radical (Asc(*)), tocopheroxyl radical (TO(*)), melanin) as markers; (ii) the
      production of short-lived radicals (hydroxyl radical (OH(*)), superoxide radical
      anion (O(2)(*-)), sulfur- and carbon-centered radicals), which are implicated in
      both, oxidative stress and redox signaling; (iii) the metabolism of nitric oxide
      (NO(*)); (iv) the antioxidative properties of various drugs, compounds, and
      natural products; (v) other redox-relevant parameter. Besides giving a
      comprehensive survey of up-to-date literature, I also provide illustrative
      examples in sufficient detail to provide a means to exploit the potential of EPR
      in biochemical/physiological/medical research. The emphasis is on the features
      and characteristics (both positive and negative) relevant for EPR application in
      clinical sciences. My aim is to encourage fellow colleagues interested in free
      radicals and antioxidants to expand their base knowledge or methods used in their
      laboratories with data acquired by EPR or some of the EPR techniques outlined in
      this review, in order to boost up the exciting area of redox science.

PMID- 21875312
TI  - Hemolyzed specimens: a major challenge for emergency departments and clinical
      laboratories.
AB  - The term hemolysis designates the pathological process of breakdown of red blood
      cells in blood, which is typically accompanied by varying degrees of red tinge in
      serum or plasma once the whole blood specimen has been centrifuged. Hemolyzed
      specimens are a rather frequent occurrence in laboratory practice, and the rate
      of hemolysis is remarkably higher in specimens obtained in the Emergency
      Department (ED) as compared with other wards or outpatient phlebotomy services.
      Although hemolyzed specimens may reflect the presence of hemolytic anemia, in
      most cases they are due to preanalytical sources related to incorrect procedures
      or failure to follow procedures for collection, handling and storage of the
      samples; some of these are typical of the ED. Since hemolyzed specimens are often
      an important cause of relationship, economic, organizational and clinical
      problems between the ED and the clinical laboratory, it is essential to develop
      effective processes for systematically identifying unsuitable specimens (e.g. by
      using the hemolysis index), differentiating in vitro from in vivo hemolysis,
      troubleshooting the potential causes, and maintaining good relations between the
      clinical laboratory and the ED.

PMID- 21875314
TI  - Changes in quality of life and their relation to cephalometric changes in
      orthognathic surgery patients.
AB  - OBJECTIVE: To evaluate correlations between presurgical and postsurgical changes
      in quality of life (QoL) and cephalometric hard and soft tissue changes in
      patients undergoing orthognathic surgery. MATERIALS AND METHODS: The study sample
      consisted of 30 patients (mean age 24.3 +/- 4.5 years) with Class III
      malocclusion undergoing orthognathic surgery for mandibular setback with a median
      follow-up of 8.3 +/- 1.2 months. Presurgical and postsurgical cephalograms were
      traced and Oral Health Impact Profile (OHIP) questionnaires were completed. Each
      questionnaire consisted of 14 items designed to evaluate functional, physical,
      psychological, and social impacts. RESULTS: Significant correlations between
      significant presurgical-to-postsurgical changes in individual items and OHIP
      parameters were found between labiomental angle (LA) and question 5 ("feeling
      self-conscious"; correlation coefficient [r]  =  0.530), between LA and question
      6 ("feeling tense"; r  =  0.598), between nasion-pogonion and question 5 (r  = 
      0.523), and between facial convexity and question 5 (r  =  -0.540). Hence,
      reduction of both LA and nasion-pogonion led to a significant decrease in the
      impact scores of items covering psychological discomfort, while reduced facial
      convexity led to increased impact scores. CONCLUSIONS: Although the associations
      were moderate, changes in QoL following cephalometric modifications should be
      considered as a major concern when planning orthognathic surgery. Postsurgical
      changes to a more convex profile after mandibular setback should be emphasized
      before surgery to help patients become accustomed to their new appearance more
      easily without negatively affecting QoL.

PMID- 21875315
TI  - Validity and reliability of a method for assessment of cervical vertebral
      maturation.
AB  - OBJECTIVE: To evaluate the validity and reliability of the cervical vertebral
      maturation (CVM) method with a longitudinal sample. MATERIALS AND METHODS: Eighty
      six cephalograms from 18 subjects (5 males and 13 females) were selected from the
      longitudinal database. Total mandibular length was measured on each film; an
      increased rate served as the gold standard in examination of the validity of the
      CVM method. Eleven orthodontists, after receiving intensive training in the CVM
      method, evaluated all films twice. Kendall's W and the weighted kappa statistic
      were employed. RESULTS: Kendall's W values were higher than 0.8 at both times,
      indicating strong interobserver reproducibility, but interobserver agreement was
      documented twice at less than 50%. A wide range of intraobserver agreement was
      noted (40.7%-79.1%), and substantial intraobserver reproducibility was proved by
      kappa values (0.53-0.86). With regard to validity, moderate agreement was
      reported between the gold standard and observer staging at the initial time
      (kappa values 0.44-0.61). However, agreement seemed to be unacceptable for
      clinical use, especially in cervical stage 3 (26.8%). CONCLUSIONS: Even though
      the validity and reliability of the CVM method proved statistically acceptable,
      we suggest that many other growth indicators should be taken into consideration
      in evaluating adolescent skeletal maturation.

PMID- 21875313
TI  - The new self-inactivating lentiviral vector for thalassemia gene therapy
      combining two HPFH activating elements corrects human thalassemic hematopoietic
      stem cells.
AB  - To address how low titer, variable expression, and gene silencing affect gene
      therapy vectors for hemoglobinopathies, in a previous study we successfully used
      the HPFH (hereditary persistence of fetal hemoglobin)-2 enhancer in a series of
      oncoretroviral vectors. On the basis of these data, we generated a novel
      insulated self-inactivating (SIN) lentiviral vector, termed GGHI, carrying the
      (A)gamma-globin gene with the -117 HPFH point mutation and the HPFH-2 enhancer
      and exhibiting a pancellular pattern of (A)gamma-globin gene expression in MEL
      585 clones. To assess the eventual clinical feasibility of this vector, GGHI was
      tested on CD34(+) hematopoietic stem cells from nonmobilized peripheral blood or
      bone marrow from 20 patients with beta-thalassemia. Our results show that GGHI
      increased the production of gamma-globin by 32.9% as measured by high-performance
      liquid chromatography (p=0.001), with a mean vector copy number per cell of 1.1
      and a mean transduction efficiency of 40.3%. Transduced populations also
      exhibited a lower rate of apoptosis and resulted in improvement of erythropoiesis
      with a higher percentage of orthochromatic erythroblasts. This is the first
      report of a locus control region (LCR)-free SIN insulated lentiviral vector that
      can be used to efficiently produce the anticipated therapeutic levels of gamma
      globin protein in the erythroid progeny of primary human thalassemic
      hematopoietic stem cells in vitro.

PMID- 21875316
TI  - The clinical and laboratory effects of bracket type during canine distalization
      with sliding mechanics.
AB  - OBJECTIVE: To compare the extent of canine movement with sliding mechanics
      between a self-ligating (SC) bracket and a modified twin design (MT) bracket. To
      test the in vitro coefficient of friction (COFs) of these two metal brackets on
      0.019- * 0.025-inch, stainless-steel arch wires. MATERIALS AND METHODS: For the
      clinical portion of this study, a split-mouth design was used to bond the
      brackets of 19 patients. Canine distalization was achieved on a 0.019- * 0.025
      inch, stainless-steel arch wire with a nickel-titanium, closed-coil spring
      strained between a mini-screw and a canine bracket. The linear and angular
      measurements were performed using lateral cephalometric radiographs taken before
      and after canine distalization. A tribometer was also used to measure the COFs of
      the bracket types in vitro. For comparisons, Student's t-tests for paired and
      unpaired samples were used at the 95% confidence level. RESULTS: The extent of
      canine movement and the changes in the canine and molar teeth angles were not
      significantly different between the SC and MT brackets. After 8 weeks, the mean
      canine movements were 1.83 and 1.89 mm in the maxilla and 1.79 mm and 1.70 mm in
      the mandible with the SC and MT brackets, respectively. The mean COF of the MT
      brackets (0.21) was significantly lower than that of the SC brackets (0.37)
      during in vitro testing. CONCLUSION: It is suggested that the rate of canine
      distalization was not different between the two groups, although in vitro COFs of
      the SC bracket was higher.

PMID- 21875317
TI  - Accuracy of a cone beam computed tomography-guided surgical stent for orthodontic
      mini-implant placement.
AB  - OBJECTIVE: To validate the accuracy of a cone-beam computed tomography (CBCT)
      guided surgical stent for orthodontic mini-implant (OMI) placement by
      quantitatively evaluating the difference between CBCT-prescribed and actual
      position of mini-implants in preoperative and postoperative CBCT images.
      MATERIALS AND METHODS: A surgical stent was fabricated using Teflon
      Perfluoroalkoxy, which has appropriate biological x-ray attenuation properties.
      Polyvinylsiloxane impression material was used to secure the custom-made surgical
      stent onto swine mandibles. CBCT scanning was done with the stent in place to
      virtually plan mini-implants using a three-dimensional (3D) software program. An
      appropriate insertion point was determined using 3D reconstruction data, and the
      vertical and horizontal angulations were determined using four prescribed angles.
      A custom-designed surveyor was used to drill a guide hole within the surgical
      stent as prescribed on the CBCT images for insertion of 32 OMIs. The mandibles
      with a surgical stent in place were rescanned with CBCT to measure the deviations
      between the virtual planning data and surgical results. RESULTS: The difference
      between the prescribed and actual vertical angle was 1.01 +/- 7.25, and the
      horizontal difference was 1.16 +/- 6.08. The correlation coefficient confirms
      that there was no intrarater variability in either the horizontal (R  =  .97) or
      vertical (R  =  .74) vectors. CONCLUSIONS: The surgical stent in this study
      guides mini-implants to the prescribed position as planned in CBCT. Since the
      statistical difference was not significant, the surgical stent can be considered
      to be an accurate guide tool for mini-implant placement in clinical use.

PMID- 21875318
TI  - Pediatric follicular lymphoma: a report of the first 3 cases from Taiwan and
      literature review.
AB  - Follicular lymphoma (FL) is a common lymphoma entity in adults but is rare in
      children. As opposed to adult cases, pediatric FL is characterized by a high
      grade histology, low-stage disease, a lower frequency of both bcl-2 protein
      expression and BCL2 gene rearrangement, and a more favorable prognosis. During
      the authors' previous study of pediatric Burkitt lymphoma, they identified 3
      cases of pediatric FL. Here the authors present the first series of pediatric FL
      from Taiwan. The patients were 2 boys and 1 girl, aged from 7 to 14. The
      presentation sites were cervical lymph node in 2 and tonsil in 1. All cases
      showed large neoplastic nodules comprising sheets of centroblasts, corresponding
      to grade 3b FL. Two of the 3 tumors weakly expressed bcl-2 protein. Fluorescence
      in situ hybridization for IGH, BCL2, BCL6, CCND1, and MYC loci showed that the
      only chromosomal translocation was rearranged IGH in 1 case. Two patients were at
      stage I, and 1 at stage III. All were treated with combination chemotherapy and
      achieved long-term complete remission. Literature review including the current
      cases showed that 45% cases of pediatric FL expressed bcl-2 protein and 9% cases
      carried BCL2 gene rearrangement, suggesting an alternate molecular pathogenesis
      of pediatric FL as compared to their adult counterparts.

PMID- 21875319
TI  - The effectiveness of recombinant human erythropoietin (EPO) treatment in a
      neonate with hyporegenerative anemia following Rh isoimmunization in spite of
      normal serum Epo level.

PMID- 21875320
TI  - Occurrence of Wilms tumor in a child with urofacial (OCHOA) syndrome.

PMID- 21875321
TI  - Pediatric acute myeloid leukemia: final frontier for pediatric oncologists in
      developing world.

PMID- 21875322
TI  - Intra-abdominal metastasis in osteosarcoma: survey and literature review.
AB  - Extrapulmonary metastasis, particularly abdominal metastasis from osteogenic
      sarcoma, are rare and generally appear as a solid mass of calcification as the
      primary tumor. The aim of this case report is to document the incidence,
      characteristics, treatment, and prognosis of abdominal metastasis in
      osteosarcomas in a single institution and to review the literature. From
      September 1989 to December 2002, 94 children <=16 years of age with osteosarcomas
      were diagnosed and treated in the Division of Pediatric Oncology, Oncology
      Institute, Istanbul University. Patients with abdominal metastasis were assessed.
      Two girls of 94 patients (2.1%) with osteosarcoma developed abdominal metastasis.
      One had pulmonary metastasis at diagnosis and the other had developed lung
      metastasis 15 months after diagnosis. They developed abdominal metastasis 4 and 3
      years after diagnosis during therapy or relapse at a median duration of 16 months
      (1-70 months) from initial diagnosis. All patients had metastasis to various
      sites, mostly lung, at the time the abdominal metastasis were detected. Treatment
      included surgery, chemotherapy, and radiotherapy in one and only surgery in the
      other patient. Both patients died at a median time of 4 months (2-6 months) from
      the time of abdominal metastasis with progressive disease. Abdominal metastasis
      in osteosarcoma is a rare event, but abdomen should be investigated in case of
      recurrence from osteosarcoma. The outcome for these patients is dismal in this
      series and in the literature.

PMID- 21875323
TI  - Unusual sites of extrapulmonary metastases of osteosarcoma after several lines of
      treatment.
AB  - The authors report a case of peritoneal and chest wall metastases in a 17-year
      old boy previously diagnosed of femur osteosarcoma with metastases in the lung
      and bones. Although the patient achieved complete remission after initial
      treatment, he presented with lung metastasis 15 months after initial diagnosis.
      They were resected 3 times and he received second-line chemotherapy with
      gemcitabine and docetaxel. However, 31 months after initial diagnosis he
      presented with abdominal and chest wall masses. In this report the authors
      discuss clinical outcomes and how unusual sites of metastasis are being
      increasingly reported after the use of new treatments.

PMID- 21875324
TI  - Potential antioxidant, antiinflammatory, and proapoptotic anticancer activities
      of Kakadu plum and Illawarra plum polyphenolic fractions.
AB  - Kakadu plum (Terminalia ferdinandiana Exell, Combretaceae) and Illawarra plum
      (Podocarpus elatus Endl., Podocarpaceae) extracts were fractionated, using a
      bioassay-guided approach and screened for antioxidant activity [oxygen radical
      absorbance capacity (ORAC) and cellular antioxidant activity (CAA) assays] and
      antiinflammatory activity (nitrite concentration and prostaglandin E(2) release
      in lipopolysaccharide (LPS)-activated murine macrophages). Among 8 fractions
      obtained from KP and 5 fractions obtained from IP, fraction KPF5 from KP
      exhibited superior activity in all assays, with an ORAC value of 3,776 +/- 603
      MUmol Trolox/g DW and a CAA value of 52.2 +/- 8.6 MUmol quercetin equivalents/g
      DW. In addition, KPF5 further demonstrated an upregulation of the Nrf2/Keap1
      ratio in Hep G2 cells. KPF5 also inhibited the expression of COX-2 and iNOS in
      LPS-activated murine macrophages, potentially through the NF-kappaB, p44/42
      mitogen activated protein kinase and Akt pathways. KPF5 also induced apoptosis
      and DNA damage in HT-29 cells, as determined by the cytokinesis block
      micronucleus cytome assay.

PMID- 21875325
TI  - Sulforaphane potentiates the efficacy of 17-allylamino 17-demethoxygeldanamycin
      against pancreatic cancer through enhanced abrogation of Hsp90 chaperone
      function.
AB  - Heat shock protein 90 (Hsp90), an essential molecular chaperone that regulates
      the stability of a wide range of oncogenic proteins, is a promising target for
      cancer therapeutics. We investigated the combination efficacy and potential
      mechanisms of sulforaphane, a dietary component from broccoli and broccoli
      sprouts, and 17-allylamino 17-demethoxygeldanamycin (17-AAG), an Hsp90 inhibitor,
      in pancreatic cancer. MTS assay demonstrated that sulforaphane sensitized
      pancreatic cancer cells to 17-AAG in vitro. Caspase-3 was activated to 6.4-fold
      in response to simultaneous treatment with sulforaphane and 17-AAG, whereas 17
      AAG alone induced caspase-3 activity to 2-fold compared to control. ATP binding
      assay and coimmunoprecipitation revealed that sulforaphane disrupted Hsp90
      p50(Cdc37) interaction, whereas 17-AAG inhibited ATP binding to Hsp90.
      Concomitant use of sulforaphane and 17-AAG synergistically downregulated Hsp90
      client proteins in Mia Paca-2 cells. Co-administration of sulforaphane and 17-AAG
      in pancreatic cancer xenograft model led to more than 70% inhibition of the tumor
      growth, whereas 17-AAG alone only suppressed the tumor growth by 50%. Our data
      suggest that sulforaphane potentiates the efficacy of 17-AAG against pancreatic
      cancer through enhanced abrogation of Hsp90 function. These findings provide a
      rationale for further evaluation of broccoli/broccoli sprout preparations
      combined with 17-AAG for better efficacy and lower dose-limiting toxicity in
      pancreatic cancer.

PMID- 21875326
TI  - Light and moderate doses of ethanol in chemical carcinogenesis of the colon in
      rats.
AB  - The aberrant crypt foci (ACF), cyclooxygenase 2 (COX-2), and the proliferating
      cell nuclear antigen (PCNA) are putative biomarkers for colon cancer. To study
      the association between light (1 g of ethanol/kg bw) and moderate (3 g of
      ethanol/kg bw) doses of ethanol with the chemical carcinogen N-methyl-N'-nitro-N
      nitrosoguanidine (MNNG), Wistar rats were divided into 6 groups. The colon
      fragments were collected for histochemical and immunohistochemical analyses, and
      the liver samples were collected for oxidative stress analysis, with products of
      lipid peroxidation (malondialdehyde), antioxidant enzymes (glutathione), and
      vitamin E. The association of light and moderate doses of ethanol with MNNG did
      not present differences in the oxidative parameters. However, a reduction in
      vitamin E levels in the carcinogen groups was observed. The association induced a
      reduction of the COX-2 and PCNA expression. The number of ACF in the group that
      received a light dose of ethanol had lower rates, while the group that received a
      moderate dose had the highest rates compared to the control MNNG, demonstrating
      that the light dose of ethanol could have a protective effect, while the moderate
      dose could represent a risk during chemical carcinogenesis in rats.

PMID- 21875327
TI  - MLH1 promoter methylation, diet, and lifestyle factors in mismatch repair
      deficient colorectal cancer patients from EPIC-Norfolk.
AB  - There is conflicting evidence for the role diet and lifestyle play in the
      development of mismatch repair (MMR)-deficient colorectal cancers (CRC). In this
      study, associations between MMR deficiency, clinicopathological characteristics,
      and dietary and lifestyle factors in sporadic CRC were investigated. Tumor
      samples from 185 individuals in the EPIC-Norfolk study were analyzed for MLH1
      gene promoter methylation and microsatellite instability (MSI). Dietary and
      lifestyle data were collected prospectively using 7-day food diaries (7dd) and
      questionnaires. MMR-deficient tumor cases (MLH1 promoter methylation positive,
      MSI-H) were more likely to be female, older at diagnosis, early Dukes' stage
      (A/B), and proximal in location (MSI-H P = 0.03, 0.03, 0.02, and 0.001,
      respectively). Tumors with positive MLH1 promoter methylation (>20%) were
      associated with poor differentiation (P = 0.03). Low physical activity was
      associated with cases without MSI (P = 0.05). MMR deficiency was not
      significantly associated with cigarette smoking or alcohol, folate, fruit,
      vegetable, or meat consumption. We conclude that MMR-deficient tumors represent a
      distinct subset of sporadic CRC that are proximal in location, early Dukes'
      stage, and poorly differentiated, in cases that are female and older at
      diagnosis. There is no overall role for diet and lifestyle in MMR status in CRC,
      consistent with age-related susceptibility to MLH1 promoter methylation.

PMID- 21875328
TI  - Advanced glycation end products, measured as skin autofluorescence, at diagnosis
      in gestational diabetes mellitus compared with normal pregnancy.
AB  - BACKGROUND: Advanced glycation end products (AGEs) are tissue proteins that
      accumulate with age and in diabetes mellitus (DM). AGEs can be measured by the
      AGE-Reader (DiagnOptics Technologies BV, Groningen, The Netherlands), which
      measures skin autofluorescence (SAF). SAF has been suggested as a measure to
      screen for undiagnosed DM or impaired glucose tolerance. SAF has never been
      investigated in gestational DM (GDM). Therefore we compared SAF at diagnosis in
      GDM patients with normal pregnancy. If SAF is elevated in GDM, future research
      could focus on the possible use of the AGE-Reader as a screening method for GDM.
      METHODS: In this monocenter observational study SAF was measured in 60 GDM
      patients at diagnosis and 44 pregnant women without diabetes. RESULTS: SAF did
      not differ between GDM at diagnosis (mean [SD], 1.74 [0.31] arbitrary units) and
      normal pregnancy (1.76 [0.32] arbitrary units). SAF was lower in white European
      patients than in patients with other ethnicity. CONCLUSIONS: This first study of
      tissue AGE accumulation in pregnancy shows no differences in SAF between women
      with GDM at diagnosis and normal pregnancy. This is most likely due to mild
      severity and short duration of hyperglycemia in GDM at diagnosis, but it does not
      exclude potential differences in SAF later in pregnancy. However, the fact that
      no differences are detected at diagnosis makes it unlikely that the AGE-Reader
      can be developed as a screening method for GDM in the future. Furthermore, we
      found that ethnicity should be taken into account when measuring SAF.

PMID- 21875329
TI  - Expansion and delivery of adipose-derived mesenchymal stem cells on three
      microcarriers for soft tissue regeneration.
AB  - Cell/microcarrier combinations can be injected to repair tissue defects, but
      whether currently available microcarriers can be utilized to repair different
      tissue defects remains unknown. Here, we compared the suitability of fabricated
      micronized acellular dermal matrix (MADM), micronized small intestinal submucosa
      (MSIS), and gelatin microspheres as expansion and delivery scaffolds for adipose
      derived mesenchymal stem cells (ADSCs). The results of MTS assay, scanning
      electron microscopy (SEM), and flow cytometry suggested that the three
      microcarriers all have good biocompatibility. Quantitative polymerase chain
      reaction revealed enhanced epidermal growth factor, vascular endothelial growth
      factor, basal fibroblast growth factor, and transforming growth factor-beta
      expression levels after ADSCs had been cultured on MADM or MSIS for 5 days. After
      culturing ADSCs on microcarriers in osteogenic medium for 7 days, the expression
      levels of bone formation-related genes were enhanced. ADSC/microcarrier treatment
      accelerated wound closure. The ADSC/MADM and ADSC/MSIS combinations retained more
      of the original implant volume at 1 month postimplantation than ADSC/gelatin
      microspheres combination in soft-tissue augmentation studies. All implants
      displayed fibroblast and capillary vessel infiltrations; but ectopic bone
      formation did not occur, and the calvarial defect repair results were
      unfavorable. Our study demonstrates the potential utility of these microcarriers
      not only as a cell-culture substrate but also as a cell-transplantation vehicle
      for skin regeneration and soft-tissue reconstruction.

PMID- 21875330
TI  - Three-dimensional visualization of bioactive glass-bone integration in a rabbit
      tibia model using synchrotron X-ray microcomputed tomography.
AB  - Synchrotron X-ray microcomputed tomography (SR microCT), with a micron
      resolution, was used to evaluate the osteoconduction and osteointegration by
      borate bioactive glass after implantation 12 weeks in a rabbit tibia model. The
      study focused on the biomaterial-bone interface. Results from SR microCT two
      dimensional and three-dimensional (3D) reconstructions provided precise imaging
      of the biomaterial-bone integration and detailed microarchitecture of both the
      bone-like glass graft and the newly formed trabecular bone. Osteoconduction, the
      formation of new trabecular bone within a tibia defect, occurred only in the
      tibiae implanted with teicoplanin-loaded borate glass but not in those with
      teicoplanin-loaded CaSO(4) beads, indicating the excellent biocompatibility of
      the glass implants. 3D reconstruction of the tibiae also showed the infiltration
      of vascular tissue in both the bioactive glass graft and the new trabecular bone.
      This study indicates that SR microCT can serve as a valuable complementary
      technique for imaging bone repair when using bioactive glass implants.

PMID- 21875331
TI  - Cardiac cell sheet transplantation improves damaged heart function via superior
      cell survival in comparison with dissociated cell injection.
AB  - Regenerative therapies have currently emerged as one of the most promising
      treatments for repair of the damaged heart. Recently, numerous researchers
      reported that isolated cell injection treatments can improve heart function in
      myocardial infarction models. However, significant cell loss due to primary
      hypoxia or cell wash-out and difficulty to control the location of the grafted
      cells remains problem. As an attempt to overcome these limitations, we have
      proposed cell sheet-based tissue engineering, which involves stacking confluently
      cultured cells (two-dimensional), cell sheets, to construct three-dimensional
      cell-dense tissues. Cell sheet transplantation has been able to recover damaged
      heart function. However, no detailed analysis for transplanted cell survival has
      been previously performed. The present study compared the survival of cardiac
      cell sheet transplantation to direct cell injection in a rat myocardial
      infarction model. Luciferase-expressing neonatal rat cardiac cells were harvested
      as cell sheets from temperature-responsive culture dishes. The transplantation of
      cell sheets was compared to the direct injection of isolated cells dissociated
      with trypsin-ethylenediaminetetraacetic acid. These grafts were transplanted to
      infarcted rat hearts and cardiac function was assessed by echocardiography at 2
      and 4 weeks after transplantation. In vivo bioluminescence and histological
      analyses were performed to examine cell survival. Cell sheet transplantation
      consistently yielded greater cell survival than cell injection.
      Immunohistochemistry revealed that cardiac cell sheets existed over the infarcted
      area as an intact layer. In contrast, the injected cells were scattered with
      relatively few cardiomyocytes in the infarcted areas. Four weeks after
      transplantation, cardiac function was also significantly improved in the cell
      sheet transplantation group compared with the cell injection. Twenty-four hours
      after cell grafting, significantly greater numbers of mature capillaries were
      also observed in the cardiac cell sheet transplantation. Additionally, the
      numbers of apoptotic cells with deterioration of integrin-mediated attachment
      were significantly lower after cardiac cell sheet transplantation. In accordance
      with increased cell survival, cardiac function was significantly improved after
      cardiac cell sheet transplantation in comparison to cell injection. Cell sheet
      transplantation can repair damaged hearts through improved cell survival and
      should become a promising therapy in cardiovascular regenerative medicine.

PMID- 21875333
TI  - Correlation of MR diffusion tensor imaging parameters with ASIA motor scores in
      hemorrhagic and nonhemorrhagic acute spinal cord injury.
AB  - This study investigated correlations between American Spinal Injury Association
      (ASIA) clinical injury motor scores in patients with traumatic cervical cord
      injury and magnetic resonance (MR) diffusion tensor imaging (DTI) parameters.
      Conventional imaging and DTI were performed to evaluate 25 patients (age, 39.7+/
      13.9 years; 4 women, 21 men) with blunt spinal cord injury and 11 volunteers
      (age, 31.5+/-10.7 years; 3 women, 8 men). Cord contusions were hemorrhagic (HC)
      in 13 and non-hemorrhagic (NHC) in 12 patients. The spinal cord was divided into
      three regions to account for spatial and pathological variation in DTI
      parameters. Comparisons of regional and injury site mean diffusivity (MD),
      fractional anisotropy (FA), radial diffusivity ( lambda(?)), and longitudinal
      diffusivity ( lambda(||)) were made with control subjects. ASIA motor scores were
      correlated with DTI using linear regression analysis. HC and NHC patients showed
      significant reduction (p<0.001) in MD and lambda(||) in all three regions. At the
      injury site, significant decreases in FA and lambda(||) were seen for both injury
      groups (p<0.001). lambda(?) values were significantly increased only for patients
      with NHC (p<0.05). Significant reduction in FA and lambda(||) (p<0.0001) was
      observed at the whole cord level between the injured (NH and NHC) and control
      groups. Within the NHC group, strong correlations were observed between ASIA
      motor scores and average MD, FA, lambda(?), and lambda(||) at the injury site.
      However, no correlation was observed within the HC group between any of the DTI
      parameters and ASIA motor scores. DTI parameters reflect the severity of spinal
      cord injury and correlate well with ASIA motor scores in patients with NHC.

PMID- 21875332
TI  - Post-injury administration of the mitochondrial permeability transition pore
      inhibitor, NIM811, is neuroprotective and improves cognition after traumatic
      brain injury in rats.
AB  - Mitochondrial dysfunction is known to play a pivotal role in cell death
      mechanisms following traumatic brain injury (TBI). N-methyl-4-isoleucine
      cyclosporin (NIM811), a non-immunosuppressive cyclosporin A (CsA) analog,
      inhibits the mitochondrial permeability transition pore (mPTP) and has been shown
      to be neuroprotective following TBI in mice. However, the translation of the
      neuroprotective effects of mPTP inhibitors, including CsA and NIM811, into
      improved cognitive end points has yet to be fully investigated. Therefore, to
      build upon these results, a severe unilateral controlled cortical impact model of
      TBI was used in the present study to establish a dose-response curve for NIM811
      in rats. The findings demonstrate that the neuroprotection afforded by NIM811 is
      dose dependent, with the 10 mg/kg dose being the most effective dose. Once the
      dose response was established, we evaluated the effect of the optimal dose of
      NIM811 on behavior, mitochondrial bioenergetics, and mitochondrial oxidative
      damage following TBI. For behavioral studies, rats were administered NIM811 at 15
      min and 24 h post-injury, with cognitive testing beginning 10 days post-injury.
      Mitochondrial studies involved a single injection of NIM811 at 15 min post-injury
      followed by mitochondrial isolation at 6 h post-injury. The results revealed that
      the optimal dose of NIM811 improves cognition, improves mitochondrial
      functioning, and reduces oxidative damage following TBI.

PMID- 21875334
TI  - A potent oncolytic adenovirus selectively blocks the STAT3 signaling pathway and
      potentiates cisplatin antitumor activity in ovarian cancer.
AB  - Cisplatin-centered chemotherapy is the first-line treatment for human ovarian
      cancer. However, chemoresistance remains a major obstacle to successful
      treatment. Evidence has indicated that signal transducer and activator of
      transcription-3 (STAT3) is a determinant of chemoresistance; it was related to
      tumor recurrence in a large number of solid malignancies. Unfortunately, none of
      the compounds currently developed to block STAT3 signaling has been considered a
      serious clinical candidate because of toxicity or limited bioavailability. In
      this study, we clarified the significance of STAT3 activation in chemoresistant
      ovarian cancer and assessed the suitability of a novel oncolytic adenovirus (M4)
      designed to specifically deplete STAT3 and reverse cisplatin resistance in
      ovarian cancer. We showed that aberrant expression and constitutive activation of
      STAT3 was instrumental in cisplatin resistance in ovarian cancer cell lines and
      in ovarian cancer tissue samples. The M4 adenovirus could specifically deplete
      constitutive and inducible STAT3 and phosphorylated STAT3 proteins in ovarian
      cancer cells. This significantly inhibited cell survival and enhanced cisplatin
      induced apoptosis. In contrast, normal human umbilical vein endothelial cells and
      human ovarian surface epithelial cells appeared to be unaffected by M4 treatment.
      Furthermore, a combined cisplatin plus M4 therapy substantially eliminated
      populations enriched in tumor-initiating cells. In mice, systemic intraperitoneal
      administration of M4 significantly potentiated the antitumor effect of cisplatin.
      These results suggest that M4 has great potential as a therapy against cisplatin
      resistance in human ovarian cancer. Thus, it warrants further clinical
      investigation.

PMID- 21875335
TI  - Treatment of metabolic syndrome slows progression of diabetic nephropathy.
AB  - BACKGROUND: Metabolic syndrome contributes to the development of albuminuria and
      to the decrease of glomerular filtration rate (GFR) in type 2 diabetes patients.
      The aim of this study was to analyze the effect of MS treatment on the
      progression of diabetic nephropathy (DN). METHODS: This was a retrospective and
      comparative cohort study. Baseline and follow-up data related to the presence of
      metabolic syndrome, microalbuminuria (mA), and GFR were obtained in individuals
      with type 2 diabetes. Subjects were classified in two groups: (1) With correction
      of metabolic syndrome and (2) without correction of metabolic syndrome at follow
      up. Furthermore, they were stratified in four subgroups: (A) Without metabolic
      syndrome at baseline and at follow-up, (B) with metabolic syndrome and correction
      of metabolic syndrome, (C) without metabolic syndrome and development of
      metabolic syndrome, and (D) with metabolic syndrome and persistence of metabolic
      syndrome. RESULTS: Final GFR and mA were lower and higher, respectively, in group
      2 versus 1 [89.8+/-3 2.3 vs. 98.3+/-32.0 mL/min, P=0.010, and 51.0 (13.5-195) vs.
      7.9 (4-31) mg/day, P<0.001, respectively]. Lack of metabolic syndrome correction
      [hazard ratio (HR)=2.8, 95% confidence interval (CI) 1.9-4.2, P<0.001], being in
      subgroups C (HR=2.05, 95% CI 1.03-4.1, P=0.04) and D (HR=3.3, 95% CI 2.0-5.3,
      P<0.001), and the presence of two (HR=3.4, 95% CI 1.9-6.1, P<0.001), three
      (HR=5.0, 95% CI 2.5-9.9, P<0.001), and four (HR=4.2, 95% CI 1.5-12.1, P=0.006)
      metabolic syndrome components were independent factors associated with
      development of mA in Cox regression analysis adjusted for age, gender, baseline
      mA and GFR, glycosylated hemoglobin (HbA1c), hypertension, and obesity.
      CONCLUSIONS: Metabolic syndrome treatment and control are independently
      associated with a lesser progression of DN.

PMID- 21875336
TI  - The waist circumference of risk in black South african men is lower than in men
      of European ancestry.
AB  - BACKGROUND: Central obesity measured by waist circumference is a cardiovascular
      disease (CVD) risk factor; however, the waist circumference of risk in
      populations of African descent has not been identified. The International
      Diabetes Federation currently suggests that cutoffs established in men of
      European descent be applied to sub-Saharan men-a waist circumference >=94 cm.
      SUBJECTS AND METHODS: Participants were 203 South African black men with type 2
      diabetes mellitus (T2DM). They were divided into quartiles of waist circumference
      (>88 cm, 88-94 cm, 95-103 cm, >103 cm). Cardiovascular risk factors, including
      insulin resistance (IR), measured by modified homeostasis model assessement of IR
      (HOMA-IR), and the triglycerides-to-high-density lipoprotein cholesterol (TG-to
      HDL-C) ratio, were compared across quartiles. RESULTS: Age, duration of diabetes,
      glycosylated hemoglobin (HbA1c), blood pressure, urinary albumin excretion, and
      smoking were similar across waist circumference quartiles. Overall, for both
      lipids and measures of IR, there was variation across waist circumference
      quartiles, but no significant differences between quartiles 2 and 3. Therefore,
      data from these two quartiles were pooled. Between the first and second+third (88
      103 cm) quartiles, there were significant differences in HDL-C (1.30+/-0.43,
      1.10+/-0.43 mmol/L, P=0.003), TG (medians 1.10, 1.60 mmol/L P<0.001), low-density
      lipoprotein cholesterol (LDL-C; 2.40+/-0.93, 2.85+/-1.03 mmol/L, P=0.01), non-HDL
      C (3.05+/-1.18, 3.70+/-1.16 mmol/L, P=0.002), HOMA-IR (medians 0.90, 2.10,
      P<0.001), and TG-to-HDL-C ratio (medians 0.89, 1.17, P<0.001). Additional
      comparisons were made between men with waist circumference <90 cm and 90-93 cm.
      Values for each lipid and for IR parameters were more favorable in the <90-cm
      group (all P<0.05). CONCLUSIONS: For black South African diabetic men, CVD risk
      substantially increased with waist circumference >90 cm. The waist circumference
      cut point of >94 cm has the potential to misclassify many black South African
      diabetic men at risk for CVD.

PMID- 21875337
TI  - The importance of sample size in the determination of a flock-level antimicrobial
      resistance profile for Escherichia coli in broilers.
AB  - Determining herd- or flock-specific antimicrobial resistance profiles is
      important to guide therapeutic use of antimicrobials and to assess risk factors
      for the development and spread of antimicrobial resistance. As such, it is of
      utmost importance to optimize the sampling strategy for the determination of herd
      specific antimicrobial resistance profiles. However, the multitude of prevalences
      measured at the same time as well as the presence of variation both at the level
      of the animal and the bacterial population of concern make it impossible to use
      conventional sample size determination methods. In this article, the use of
      bootstrapping techniques for sample size determination was explored. In
      particular, one-stage and two-stage bootstrap samplings were used to determine
      the optimal number of animals and the optimal number of isolates within one
      animal. Results show that focus should be on the number of animals sampled rather
      than on the number of isolates tested within one animal.

PMID- 21875338
TI  - In vitro activity of tigecycline and comparators against gram-negative bacteria
      isolated from a tertiary hospital in Alexandria, Egypt.
AB  - The emergence of infections caused by multidrug-resistant Gram-negative bacteria,
      in particular Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella
      pneumoniae, has necessitated the search for alternative therapy by either
      introducing new agents or renewing interest in old agents. This study compares
      the in vitro activity of tigecycline (TIG), recently introduced to Egyptian
      market, to other potentially active antimicrobials as Colistin (COL), imipenem
      (IPM), levofloxacin (LEV), and piperacillin/tazobactam (PIP/TAZ) against 67 Gram
      negative clinical isolates obtained from El- Meery Hospital in Alexandria, Egypt.
      El-Meery Hospital is a 1,500-bed tertiary teaching hospital where TIG has not
      been previously used. Based on MIC(90)s, TIG was found to be a comparator to IPM
      and COL (MIC(90)= 8 MUg/ml). LEV and PIP/TAZ were less active than TIG exhibiting
      high MIC(90)s. TIG inhibited 100% of Escherichia coli and K. pneumoniae and 60%
      of Ps. aeruginosa and A. baumannii isolates. In time-kill studies against IPM
      resistant isolates, TIG showed bactericidal activity after 6 hours of contact
      against the Enterobacteriaceae isolates and after 3 hours for the tested Ps.
      aeruginosa isolates at 4* and 8* MIC. Against A. baumannii, TIG exerted a
      bacteriostatic effect. TIG demonstrated variable ability to suppress biofilm
      formation affecting mainly E. coli and A. baumannii isolates. These results point
      TIG to be a promising agent in treatment of infections caused by strains for
      which adequate therapy has been limited. As far as we know, this is the first
      report evaluating the in vitro activity of TIG against Egyptian clinical
      isolates.

PMID- 21875339
TI  - Histology of a paraumbilical band in a neonate with gastroschisis.
AB  - We report a case of gastroschisis in which a paraumbilical band was found at the
      right margin of the abdominal wall defect and extended into the antimesenteric
      side of the small intestine. The band consisted of 2 thin cords. Microscopically,
      1 band showed a fibrous tissue, and the other 1 revealed a unique vascular
      structure resembling the vitelline artery and vein, suggesting that the
      paraumbilical band represents a remnant of the yolk stalk that failed to be
      incorporated into the umbilical stalk. The origin of the paraumbilical band and
      an associated pathogenetic hypothesis of gastroschisis are discussed.

PMID- 21875340
TI  - Ductus arteriosus aneurysm with massive thrombosis of pulmonary artery and fetal
      hydrops.
AB  - Ductus arteriosus aneurysm (DAA) is a rare cardiovascular lesion usually
      diagnosed within the first 2 months of life, or less frequently in the 3rd
      trimester, by antenatal sonography. The true in utero incidence of DAA is
      unknown, as most affected fetuses are asymptomatic at birth. Potential
      complications include thromboembolism, rupture, and death. We report a unique
      lethal case of a large DAA detected by mid-2nd trimester fetal echocardiography,
      complicated by stricture and massive occlusive thrombosis extending into the
      pulmonary artery branches. Stricture and thrombosis of the DAA led to
      interruption of fetal circulation, cardiac failure, and fetal hydrops, ultimately
      resulting in fetal demise.

PMID- 21875341
TI  - Hypoxia enhances the generation of retinal progenitor cells from human induced
      pluripotent and embryonic stem cells.
AB  - The efficient differentiation of retinal cells from human pluripotent stem cells
      remains a major challenge for the development of successful and cost-effective
      cellular therapies for various forms of blindness. Current differentiation
      strategies rely on exposing pluripotent stem cells to soluble growth factors that
      play key roles during early development (such as DKK-1, Noggin, and IGF-1) at 20%
      oxygen (O(2)). This O(2) tension is, however, considerably higher than O(2)
      levels during organogenesis and may impair the differentiation process. In this
      study, we examined the effect of mimicking the physiological O(2) tension (2%) on
      the generation of retinal progenitor cells (RPCs) from human induced pluripotent
      stem cells (iPSCs) and human embryonic stem cells (hESCs). Both cell types were
      induced to differentiate into RPCs at 20% and 2% O(2). After 3 days in suspension
      culture as embryoid bodies (EBs), 2% O(2) caused the activation of hypoxia
      inducible factor responsive genes VEGF and LDHA and was accompanied by elevated
      expression levels of the early eye field genes Six3 and Lhx2. Twenty-one days
      after plating EBs in an adherent culture, we observed more RPCs co-expressing
      Pax6 and Chx10 at 2% O(2). Quantitative polymerase chain reaction analysis
      confirmed that lowering O(2) tension had caused a rise in the expression of both
      genes compared with 20% O(2). Our results indicate that mimicking physiological
      O(2) is a favorable condition for the efficient generation of RPCs from both
      hiPSCs and hESCs.

PMID- 21875342
TI  - Emergence of extended-spectrum beta-lactamase-producing escherichia coli as a
      cause of community-onset bacteremia in South Korea: risk factors and clinical
      outcomes.
AB  - To define the risk factors and clinical outcomes of community-onset bacteremia
      caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli
      (ESBLEC), we analyzed 50 consecutive cases of community-onset bacteremia caused
      by ESBLEC at a secondary hospital in South Korea from 2005 to 2010. Risk factors
      were assessed by conducting a case-double control study in which cases were
      compared with (1) control patients with community-onset bacteremia due to non
      ESBLEC, and (2) those with community-onset bacteremia not caused by E. coli.
      Clinical outcome was assessed among patients with community-onset E. coli
      bacteremia. Community-onset bacteremia due to ESBLEC accounted for 6.7% of all
      community-onset E. coli bacteremia. In addition, an increasing proportion of
      ESBLEC among patients without any healthcare risk factors was observed.
      Comparison with both control groups revealed that the recent use of antibiotics
      (odds ratio [OR], 4.3; 95% confidence interval [CI], 1.5-12.3) was an independent
      risk factor for ESBL acquisition. Factors influencing the 30-day mortality were a
      high Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR, 1.5;
      95% CI, 1.1-2.0) and severe sepsis or septic shock (OR, 26.6; 95% CI, 1.5-470.7)
      and malignancy (OR, 11.9; 95% CI, 1.1-134.8). Increased mortality was not
      statistically associated either with ESBL production or with inappropriate
      empirical therapy. ESBLEC has emerged as a significant cause of community-onset
      bacteremia in this hospital, suggesting that ESBLEC are widely disseminated in
      the South Korean community.

PMID- 21875343
TI  - The association of HIV status with bacterial vaginosis and vitamin D in the
      United States.
AB  - OBJECTIVE: To estimate the association between vitamin D deficiency and bacterial
      vaginosis (BV) among nonpregnant HIV-infected and uninfected women. METHODS: In a
      substudy of the Women's Interagency HIV Study, including women from Chicago and
      New York, the association between BV and vitamin D deficiency, demographics, and
      disease characteristics was tested using generalized estimating equations.
      Deficiency was defined as <20 ng/mL 25 (OH) vitamin D and insufficiency as >20
      and <=30 ng/mL. BV was defined by the Amsel criteria. RESULTS: Among 602
      observations of nonpregnant women (480 HIV infected and 122 uninfected), BV was
      found in 19%. Vitamin D deficiency was found in 59.4%, and insufficiency was
      found in 24.4%. In multivariable analysis, black race was the most significant
      predictor of BV (adjusted odds ratio [AOR] 5.90, (95% confidence interval [CI]
      2.52-13.8). Vitamin D deficiency was independently associated with BV among HIV
      infected women (AOR 3.12, 95% CI 1.16-8.38) but not among HIV-uninfected women.
      There was a negative linear correlation between vitamin D concentration and
      prevalence of BV in HIV-infected women (r=-0.15, p=0.001). CONCLUSIONS: Vitamin D
      deficiency was very common in this cohort and significantly associated with BV
      among HIV-infected women. These preliminary findings suggest that further
      epidemiologic and mechanistic exploration of the relationship between vitamin D
      and BV in HIV-infected women is warranted.

PMID- 21875344
TI  - Thyrotoxicosis-induced acute myocardial infarction due to painless thyroiditis.
AB  - BACKGROUND: Thyrotoxicosis influences cardiovascular hemodynamics and can induce
      coronary vasospasm. Patients with thyrotoxicosis-induced acute myocardial
      infarction (AMI) are unusual and almost all reported cases have been associated
      with Graves' disease. Patients with painless thyroiditis show a thyrotoxic phase
      during the early stages. Here we describe a very rare case of thyrotoxicosis with
      painless thyroiditis-induced AMI. SUMMARY: A 35-year-old Korean man visited the
      emergency room for a 2-hour duration of typical AMI chest pain. The patient did
      not have any coronary artery disease (CAD) risk factors. The electrocardiogram
      showed 3 mm of ST-segment elevation in leads II, III, and aVF, which is
      consistent with inferior AMI. We immediately treated the patient with aspirin,
      clopidogrel, and nitroglycerine and performed emergent coronary angiography.
      Coronary angiography showed normal coronary arteries without any stenotic
      lesions. Consistent with AMI, cardiac enzyme levels of serum creatine kinase
      (CK), CK-MB, and troponin-I were also elevated. Laboratory findings showed
      thyrotoxicosis without any thyroid autoantibodies. A 99m-technetium scintigraphy
      showed markedly decreased thyroid uptake compatible with thyroiditis. We treated
      the patient with calcium channel blockers and nitrates. The patient spontaneously
      recovered normal thyroid function after 6 weeks of observation and did not
      complain of chest pain. CONCLUSION: Thyrotoxicosis due to painless thyroiditis
      provoked AMI in a young man who had no atherosclerotic coronary lesions and no
      CAD risk factors.

PMID- 21875345
TI  - Maternal thyroid function at eleven to thirteen weeks of gestation and subsequent
      delivery of small for gestational age neonates.
AB  - BACKGROUND: Studies have shown that altered thyroid function in early pregnancy
      may affect normal placental development and hence fetal growth. Our hypothesis is
      that maternal thyroid function in the first trimester is altered in pregnancies
      that subsequently deliver small for gestational age (SGA) neonates. METHODS:
      Maternal serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free
      triiodothyronine (FT3) were measured at 11(+0) to 13(+6) weeks' gestation in 212
      singleton pregnancies with no history of thyroid disease that subsequently
      delivered SGA neonates and the values were compared with the results of 3598
      normal pregnancies delivering neonates with birth weight above the 5th percentile
      for gestation. RESULTS: There were no significant differences between the normal
      and SGA groups in median multiple of the median (MoM) TSH (1.07 vs. 1.061 MoM),
      FT4 (0.992 vs. 1.010 MoM), and FT3 (0.991 vs. 0.990 MoM). CONCLUSION: In women
      with no history of thyroid disease delivering SGA neonates, thyroid function
      during the first trimester of pregnancy is not significantly different from women
      delivering non-SGA neonates.

PMID- 21875346
TI  - Altered expression of the gap junction protein connexin43 is associated with
      papillary thyroid carcinomas when compared with other noncancer pathologies of
      the thyroid.
AB  - BACKGROUND: Gap junctions are membrane structures composed of connexins (Cx) that
      allow diffusion of small molecules between cells. They are involved in tissue
      homeostasis, and various organ dysfunctions have been associated with gap
      junction defects. To verify their possible involvement in thyroid pathologies,
      the expression of connexin43 (Cx43), the major Cx in the human thyroid, was
      evaluated in a variety of diseases including cancer. METHODS: There were 122
      samples from various thyroid pathologies that were collected to analyze the
      presence of Cx43 by immunofluorescence. Through confocal microscopy, different
      patterns of Cx43 localization were identified as normal (membrane) or abnormal
      (cytoplasmic or lack of detection). The analysis of Cx43 expression was further
      performed by quantitative reverse transcriptase-polymerase chain reaction and
      immunohistochemistry in a subset of 25 papillary carcinomas and compared with
      nontumoral thyroid tissues. RESULTS: The presence of Cx43 was commonly altered in
      thyroid cancer, as abnormal Cx43 staining was detected in 94.1% of cancer, 47.4%
      of adenomas, 45.7% of multinodular goiter, 16.7% of Graves' disease, and 25% of
      thyroiditis. In papillary carcinoma samples, the deregulation of Cx43 expression
      was mostly the consequence of a decrease of Cx43 mRNA (68% of cases) when
      compared with normal tissue. When Cx43 mRNA was not downregulated (32% of cases),
      both loss of membrane staining and aberrant cytoplasmic distribution of the
      protein were observed. CONCLUSIONS: These results show that aberrations of Cx43
      expression are associated with thyroid papillary carcinoma.

PMID- 21875348
TI  - Frequencies and CAM united.

PMID- 21875347
TI  - Immunocytochemistry with cytokeratin 19 and anti-human mesothelial cell antibody
      (HBME1) increases the diagnostic accuracy of thyroid fine-needle aspirations:
      preliminary report of 150 liquid-based fine-needle aspirations with histological
      control.
AB  - BACKGROUND: Thyroid nodules are relatively common (7% of the population) but are
      malignant in only 5%-10% of cases. Fine-needle aspiration (FNA) to detect cancer
      can have > 90% sensitivity but only 50%-65% specificity because of false-positive
      results, which necessitates surgical controls. We aimed to assess the diagnostic
      accuracy of immunocytochemistry (ICC) of thyroid FNA to improve its sensitivity
      and specificity. METHODS: We prospectively collected 2038 thyroid FNAs, of which
      1397 were FNA biopsies with liquid-based cytology (Thin-Prep-Hologic(r)). ICC
      with cytokeratin 19 and HBME1 antibodies (Dako(r) A/S) was used for all malignant
      cases and cases of atypical cells of undetermined significance (AUS), follicular
      neoplasm (FN), and nodules suspicious for malignancy-papillary thyroid carcinoma
      (SM-PTC) as well as some benign cases (abnormal features on radiography or benign
      on secondary FNA). ICC results were defined as "non-contributory," "favoring
      benign," "favoring malignant," or "indeterminate." Results for 150 cases were
      compared with histological controls for diagnostic accuracy. RESULTS: Of these
      150 cases ICC was helpful for benign or malignant triage of 48 cases of AUS, FN,
      and SM-PTC (42% of these lesions). Six (4%) ICC results were false positive
      (favoring malignant with benign histology) but none were false negative (favoring
      benign with malignant histology). Results for indeterminate cytological cases
      favored malignant or benign disease with sensitivity, specificity, and negative
      and positive predictive values of 100%, 85.2%, 100%, and 86.2%, respectively.
      CONCLUSIONS: ICC of thyroid FNAs with cytokeratin 19 and HBME1 antibodies can
      reduce the false-positive and false-negative results of single morphological
      analyses. It can increase the sensitivity and specificity of diagnosis, thus
      improving diagnostic accuracy and reducing the need for surgical controls.

PMID- 21875349
TI  - Structural integration: origins and development.

PMID- 21875350
TI  - The assessment of complementary and alternative medicine use among individuals
      with HIV: a systematic review and recommendations for future research.
AB  - OBJECTIVES: The use of complementary and alternative medicine (CAM), a group of
      health care practices and products that are not considered part of conventional
      medicine, has increased in recent years, particularly among individuals with
      human immune deficiency virus (HIV). Assessing the prevalence and predictors of
      CAM use among HIV-positive populations is important because some CAM therapies
      may adversely affect the efficacy of conventional HIV medications. Unfortunately,
      CAM use is not comprehensively or systematically assessed among HIV-positive
      populations. Therefore, the aim of the present study was to evaluate the quality
      of the instruments employed in observational studies assessing CAM use among HIV
      positive populations by examining the degree to which these studies (1) evaluated
      the psychometric properties of their CAM instruments and (2) assessed the
      multidimensional nature of CAM use. DESIGN: A systematic review of studies was
      undertaken and specific review criteria were used to guide the inclusion of
      studies. Specifically, articles were included that were published in English and
      in a peer-reviewed journal between 1997 and 2007, recruited HIV-positive study
      participants, and assessed CAM use. Thirty-two (32) studies met these inclusion
      criteria. RESULTS: Results suggest that CAM assessment among HIV-positive
      populations continues to be problematic. For example, approximately 20% of the
      studies assessed the reliability and 3% assessed the validity of the CAM
      instrument employed. CONCLUSIONS: CAM assessment--regardless of the specific
      study population--is a complex and challenging task. However, CAM instruments
      will not become more refined over time in the absence of rigorous psychometric
      evaluation. Future research must assess reliability and validity and report these
      data in a clear and nuanced manner.

PMID- 21875351
TI  - Effects of oral glutathione supplementation on systemic oxidative stress
      biomarkers in human volunteers.
AB  - BACKGROUND: The tripeptide glutathione (GSH) is the most abundant free radical
      scavenger synthesized endogenously in humans. Increasing mechanistic, clinical,
      and epidemiological evidence demonstrates that GSH status is significant in acute
      and chronic diseases. Despite ease of delivery, little controlled clinical
      research data exist evaluating the effects of oral GSH supplementation.
      OBJECTIVES: The study objectives were to determine the effect of oral GSH
      supplementation on biomarkers of systemic oxidative stress in human volunteers.
      DESIGN: This was a randomized, double-blind, placebo-controlled clinical trial.
      SETTING/LOCATION: The study was conducted at Bastyr University Research
      Institute, Kenmore, WA and the Bastyr Center for Natural Health, Seattle, WA.
      SUBJECTS: Forty (40) adult volunteers without acute or chronic disease
      participated in this study. INTERVENTION: Oral GSH supplementation (500 mg twice
      daily) was given to the volunteers for 4 weeks. OUTCOME MEASURES: Primary outcome
      measures included change in creatinine-standardized, urinary F2-isoprostanes (F2
      isoP) and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Changes in erythrocyte
      GSH concentrations, including total reduced glutathione (GSH), oxidized
      glutathione (GSSG), and their ratio (GSH:GSSG) were also measured by tandem
      liquid chromatography/mass spectrometry. Analysis of variance was used to
      evaluate differences between groups. RESULTS: There were no differences in
      oxidative stress biomarkers between treatment groups at baseline. Thirty-nine
      (39) participants completed the study per protocol. Changes in creatinine
      standardized F2-isoP (ng/mg creatinine) (0.0+/-0.1 versus 0.0+/-0.1, p=0.38) and
      8-OHdG (MUg/g creatinine) (-0.2+/-3.3 versus 1.0+/-3.2, p=0.27) were
      nonsignificant between groups at week 4. Total reduced, oxidized, and ratio
      measures of GSH status were also unchanged. CONCLUSIONS: No significant changes
      were observed in biomarkers of oxidative stress, including glutathione status, in
      this clinical trial of oral glutathione supplementation in healthy adults.

PMID- 21875352
TI  - Lymphedema after breast or gynecological cancer: use and effectiveness of
      mainstream and complementary therapies.
AB  - OBJECTIVES: The purpose of this study was to describe the use, as well as
      perceived effectiveness, of mainstream and complementary and alternative medicine
      (CAM) therapies in the treatment of lymphedema following breast or gynecological
      cancer. Further, the study assessed the relationship between the characteristics
      of lymphedema (including type, severity, stability, and duration), and the use of
      CAM and/or mainstream treatment. METHODS: This was a cross-sectional study using
      a convenience sample of women with lymphedema following breast and gynecological
      cancers. A self-administered questionnaire was sent to 247 potentially eligible
      women. Of those returned (50%), 23 were ineligible and 6 were excluded due to
      level of missing data. RESULTS: In the previous 12 months, the majority of women
      (90%) had used mainstream treatments to treat their lymphedema, with massage
      being the most commonly used (86%). One (1) in 2 women had used CAM to treat
      their lymphedema, and 98% of those using CAM were also using mainstream
      treatments. Over 27 types of CAM were reported, with use of a chi machine,
      vitamin E supplements, yoga, and meditation being the most commonly reported
      forms. The perceived effectiveness ratings (1-7 with 7=completely effective) of
      mainstream (mean+/-standard deviation (SD): 5.3+/-1.5) and CAM therapies (mean+/
      SD: 5.2+1.6) were considered high. CONCLUSIONS: These results demonstrate that
      mainstream and CAM treatment use is common, varied, and considered to be
      effective among women with lymphedema following breast or gynecological cancer.
      Furthermore, it highlights the immediate need for larger prospective studies
      assessing the inter-relationship between the use of mainstream and CAM therapies
      for treatment success.

PMID- 21875353
TI  - Necrotizing fasciitis after acupuncture in a patient with aplastic anemia.
AB  - OBJECTIVES: The objective of this study was to describe a serious complication of
      acupuncture treatment in a high-risk patient with aplastic anemia. DESIGN: A 44
      year-old woman with aplastic anemia experienced right calf pain after running.
      After poor results with physical therapy, she received needle acupuncture for
      pain relief. However, aggravated pain with swelling of the right calf developed 2
      days later. RESULTS: On admission, she had a temperature of 38.8 degrees C, a
      white blood cell count of 500/MUL, and hemoglobin of 5.7 g/dL. Ultrasound and
      computed tomography scans showed swelling of the right calf muscle fascia, and
      aspiration drew out Staphylococcus infection. The symptoms improved after
      treatment with parenteral antibiotics. CONCLUSIONS: This case illustrates that
      necrotizing fasciitis must be considered as a possible complication of
      acupuncture in high-risk patients, and that early recognition and treatment of
      this life-threatening soft-tissue infection must be emphasized. Extreme caution
      should be employed when using acupuncture for high-risk patients, such as those
      with aplastic anemia.

PMID- 21875354
TI  - Pleasure to play, arousal to stay: the effect of player emotions on digital game
      preferences and playing time.
AB  - This study investigated how player emotions during game-play, measured through
      self-report and physiological recordings, predict playing time and game
      preferences. We distinguished between short-term (immediately after game-play)
      and long-term (after 3 weeks) playing time and game preferences. While pleasure
      was most predictive for short-term playing time and game preferences, arousal,
      particularly for game preferences, was most predictive on the longer term. This
      result was found through both self-report and physiological emotion measures.
      This study initiates theorizing about digital gaming as a hedonic consumer
      product and sketches future research endeavors of this topic.

PMID- 21875355
TI  - Implementation and experience of an alternative QF-PCR and MLPA diagnostic
      strategy to detect chromosomal abnormalities in fetal and neonatal pathology
      samples.
AB  - Chromosomal abnormalities are a significant cause of pregnancy loss. Solid tissue
      fetal and neonatal pathology samples are routinely examined by karyotype analysis
      after cell culture. However, there is a high failure rate, and this approach is
      expensive and labor intensive. We have therefore evaluated a new molecular
      strategy involving quantitative fluorescent polymerase chain reaction (QF-PCR)
      and subtelomere multiplex ligation-dependent probe amplification (MLPA) analysis.
      A retrospective audit showed that less than 4% of abnormal cases may not be
      detected by this molecular strategy. We validated this strategy in parallel with
      cytogenetic analysis on 110 patient samples, which included cases of fetal loss,
      still birth, neonatal death, termination of pregnancy, recurrent miscarriage, and
      sudden unexpected death in infancy. This validation showed that 55 of the 57
      samples that gave a result for both strategies were concordant. During the 1st
      year of diagnostic testing, we analyzed 382 samples by the molecular strategy. A
      16% abnormality rate was observed. These included trisomies 13, 18, 21, monosomy
      X, and triploidy detected by QF-PCR (77%), and 23% were other trisomies and
      subtelomere imbalances detected by MLPA. This strategy had a 92% success rate in
      contrast to the 20%-30% failure rate observed with cell culture and cytogenetic
      analysis. We conclude that QF-PCR and subtelomere MLPA is a suitable strategy for
      analysis of the majority of fetal and neonatal pathology samples, with many
      advantages over conventional cytogenetic analysis.

PMID- 21875356
TI  - Potential fossil endoliths in vesicular pillow basalt, Coral Patch Seamount,
      eastern North Atlantic Ocean.
AB  - The chilled rinds of pillow basalt from the Ampere-Coral Patch Seamounts in the
      eastern North Atlantic were studied as a potential habitat of microbial life. A
      variety of putative biogenic structures, which include filamentous and spherical
      microfossil-like structures, were detected in K-phillipsite-filled amygdules
      within the chilled rinds. The filamentous structures (~2.5 MUm in diameter) occur
      as K-phillipsite tubules surrounded by an Fe-oxyhydroxide (lepidocrocite) rich
      membranous structure, whereas the spherical structures (from 4 to 2 MUm in
      diameter) are associated with Ti oxide (anatase) and carbonaceous matter. Several
      lines of evidence indicate that the microfossil-like structures in the pillow
      basalt are the fossilized remains of microorganisms. Possible biosignatures
      include the carbonaceous nature of the spherical structures, their size
      distributions and morphology, the presence and distribution of native
      fluorescence, mineralogical and chemical composition, and environmental context.
      When taken together, the suite of possible biosignatures supports the hypothesis
      that the fossil-like structures are of biological origin. The vesicular
      microhabitat of the rock matrix is likely to have hosted a cryptoendolithic
      microbial community. This study documents a variety of evidence for past
      microbial life in a hitherto poorly investigated and underestimated
      microenvironment, as represented by the amygdules in the chilled pillow basalt
      rinds. This kind of endolithic volcanic habitat would have been common on the
      early rocky planets in our Solar System, such as Earth and Mars. This study
      provides a framework for evaluating traces of past life in vesicular pillow
      basalts, regardless of whether they occur on early Earth or Mars.

PMID- 21875357
TI  - Native molecular state of adeno-associated viral vectors revealed by single
      molecule sequencing.
AB  - The single-stranded genome of adeno-associated viral (AAV) vectors is one of the
      key factors leading to slow-rising but long-term transgene expression kinetics.
      Previous molecular studies have established what is now considered a textbook
      molecular model of AAV genomes with two copies of inverted tandem repeats at
      either end. In this study, we profiled hundreds of thousands of individual
      molecules of AAV vector DNA directly isolated from capsids, using single-molecule
      sequencing (SMS), which avoids any intermediary steps such as plasmid cloning.
      The sequence profile at 3' ends of both the regular and oversized vector did show
      the presence of an inverted terminal repeat (ITR), which provided direct
      confirmation that AAV vector packaging initiates from its 3' end. Furthermore,
      the vector 5'-terminus profile showed inconsistent termination for oversized
      vectors. Such incomplete vectors would not be expected to undergo canonical
      synthesis of the second strand of their genomic DNA and thus could function only
      via annealing of complementary strands of DNA. Furthermore, low levels of
      contaminating plasmid DNA were also detected. SMS may become a valuable tool
      during the development phase of vectors that are candidates for clinical use and
      for facilitating/accelerating studies on vector biology.

PMID- 21875358
TI  - A transductionally retargeted adenoviral vector for virotherapy of Her2/neu
      expressing prostate cancer.
AB  - The efficacy of adenovirus (Ad)-based gene therapy of solid tumors, such as
      prostate cancer, is limited. One of the many problems is that the virus infects
      many different cell types in the body, resulting in high toxicity, whereas the
      target cancer cells are often less prone to wild-type Ad infection. Our aim was
      to develop genetically de- and retargeted Ad vectors to reduce off-target effects
      and increase target infection for prostate cancer. We have previously reported an
      Ad5 vector specific for the cancer-associated receptor Her2/neu, created by
      inserting Her2/neu-reactive Affibody((r)) molecules (ZH) into the HI loop of a
      coxsackievirus and adenovirus receptor binding-ablated fiber (Ad[ZH/1]). In
      addition to virus retargeting to Her2/neu, this virus was further modified from
      wild-type Ad by changing the RGD motif in the penton base to EGD and by
      substitution of the KKTK motif in the third shaft repeat to RKSK, resulting in
      the vector Ad[ZH/3]. The ZH-containing vectors could be produced to high titers
      and were specific for their target, resulting in efficient infection and killing
      of Her2/neu-positive androgen-dependent PC346C prostate cancer cells in vitro.
      Here we show that the oncolytic Ad[ZH/3] vector significantly prolonged survival
      time and reduced serum prostate-specific antigen levels in an orthotopic prostate
      tumor model in nude mice to the same extent as wild-type Ad5. Our results show
      that Her2/neu targeting using Ad-based vectors for prostate cancer is feasible
      and may serve as a basis for the development of gene therapy of human prostate
      cancer as well as other Her2/neu-expressing cancers.

PMID- 21875359
TI  - Human mesenchymal stem cells induced by growth differentiation factor 5: an
      improved self-assembly tissue engineering method for cartilage repair.
AB  - Previous studies have shown that novel scaffold-free self-assembled constructs
      can be an ideal alternative for cartilage tissue engineered based on scaffolds,
      which has many limitations. However, many questions remain, including the choice
      of seeding cells and the role of growth differentiation factor 5 (GDF-5) in
      constructing self-assembled engineered cartilages. Moreover, whether the optimum
      construct is effective in human chondral defect repair is still unknown. In this
      study, we generated self-assembled constructs of human mesenchymal stem cells
      (hMSCs) using four different approaches: direct self-assembly of hMSCs with or
      without GDF-5, and predifferentiated hMSCs self-assembly with or without GDF-5.
      Histological, immunohistochemical, and biochemistry analyses indicated that the
      constructs generated from predifferentiated hMSCs induced by GDF-5 (Group D2)
      exhibited up-regulated glycosaminoglycan (GAG) and type II collagen expression
      and contained higher amounts of GAG and total collagen than any other group.
      After 3-weeks of in vitro culturing of the constructs in a chondral defects
      explant culture system, the contructs from Group D2 were stably adhered to the
      surface of the cartilage matrix. Immunohistochemically, the repair tissue was
      positive for type II collagen, toluidine blue, and safranin O. These data
      demonstrated that the generation of self-assembled tissue-engineered cartilage
      from chondrogenically differentiated hMSCs induced by GDF-5 is a promising
      therapeutic strategy for cartilage repair.

PMID- 21875361
TI  - Evolution of multidrug-resistant Staphylococcus aureus infections in horses and
      colonized personnel in an equine clinic between 2005 and 2010.
AB  - A total of 70 Staphylococcus aureus isolates from postoperative infections in
      hospitalized horses were isolated between January 2005 and January 2011. Among
      them, 12 isolates were methicillin-susceptible S. aureus (MSSA), 18 were
      borderline-oxacillin-resistant S. aureus (BORSA), and 40 were methicillin
      resistant S. aureus (MRSA). During the same period, the equine clinic personnel
      were screened for nasal carriage of BORSA and MRSA. Genotyping revealed that
      BORSA ST1(MLST)-t2863(spa) isolates were responsible for most equine infections
      and were the main isolates found in colonized members of the personnel between
      2005 and 2007, and that in 2007, MRSA ST398-t011-IVa(SCCmec) emerged in infection
      sites and personnel, replacing BORSA. Besides decreased susceptibility to
      oxacillin, all MRSA and BORSA of these two major clonal lineages displayed
      resistance to gentamicin and kanamycin conferred by the aac(6')-Ie-aph(2')-Ia
      gene and to trimethoprim conferred by dfr(K) in MRSA and dfr(A) in BORSA. All
      MRSA had additional resistance to tetracycline conferred by tet(M), whereas BORSA
      generally also display resistance to streptomycin conferred by str. The number of
      hospital-acquired MRSA infections in horses could be limited after the
      introduction of basic hygiene measures and personnel decolonization. Two MRSA
      carriers could not be decolonized using mupirocin, and a year after
      decolonization, additional members were recolonized with MRSA. Hygiene measures
      should, therefore, be maintained to limit the transmission of S. aureus between
      personnel and horses.

PMID- 21875360
TI  - Methionine sulfoximine resistance in Mycobacterium tuberculosis is due to a
      single nucleotide deletion resulting in increased expression of the major
      glutamine synthetase, GlnA1.
AB  - We investigated the effect of methionine sulfoximine (MetSox), a potent inhibitor
      of glutamine synthetase, on Mycobacterium tuberculosis. M. tuberculosis encodes
      four glutamine synthetases, of which MetSox targets the type I enzyme encoded by
      glnA1. Transcriptional profiling revealed that glutamate synthetase (gltB) and a
      type II glutamine synthetase (glnA3) were induced after exposure to MetSox. In
      addition, we observed a high rate (10(-5)) of spontaneous resistance to MetSox.
      All resistant strains had a single-nucleotide deletion in the 5' region of glnA1,
      and Western analysis revealed that GlnA1 expression was increased in resistant as
      compared with sensitive strains. These data show that M. tuberculosis can respond
      to the effect of MetSox inhibition either by up-regulation of GlnA3 or by GlnA1.
      The high frequency of resistance suggests that MetSox and other compounds
      specifically targeting GlnA1 are not likely to become successful anti
      mycobacterial agents.

PMID- 21875362
TI  - Trough insulin levels in bronchoalveolar lavage following inhaled human insulin
      (Exubera) in patients with diabetes mellitus.
AB  - BACKGROUND/AIM: There are few data regarding insulin levels in the lungs during
      diabetes therapy with inhaled insulin. We examined the disposition of inhaled
      human insulin (Exubera((r)) [EXU] human insulin [recombinant DNA origin], Pfizer,
      New York, NY) in the lungs by measuring trough insulin levels in bronchoalveolar
      lavage (BAL) fluid after 12 weeks of EXU treatment. METHODS: After a 4-week run
      in period of subcutaneous insulin therapy, 24 subjects with type 1 diabetes
      mellitus (T1DM) and 26 with type 2 diabetes mellitus (T2DM) continued their basal
      insulin regimen and received premeal subcutaneous (SC) insulin for 13 weeks,
      followed by 12 weeks of premeal EXU. BAL was performed approximately 12 h after
      the last insulin dose at (1) baseline, (2) following SC insulin, and (3)
      following EXU. RESULTS: Twenty patients with T1DM and 24 patients with T2DM
      completed all three bronchoscopies. BAL trough insulin levels were undetectable
      at baseline or following SC insulin. After EXU therapy, they increased to a
      median of 4.5 nM (1.6-9.0 nM) and 2.3 nM (0.5-9.4 nM) in T1DM and T2DM,
      respectively. BAL trough insulin levels did not correlate with treatment
      efficacy, adverse effects, plasma insulin levels, or changes in pulmonary
      function. A larger proportion of previous EXU doses was present in the BAL in
      patients with T1DM. We found no correlation between average daily insulin doses
      and BAL trough insulin levels. CONCLUSIONS: BAL trough insulin increased
      following EXU therapy, but this increase did not correlate with other clinical or
      laboratory parameters, suggesting no significant biological action. Further
      studies are warranted to better understand inhaled insulin deposition and
      clearance and possible effects of increased insulin levels on the lungs.

PMID- 21875363
TI  - Capsicum annuum L. methanolic extract inhibits ovalbumin-induced airway
      inflammation and oxidative stress in a mouse model of asthma.
AB  - The pepper fruit of Capsicum annuum L. is used as a food, spice, and topical
      medicine. Here, we investigated the effect of a methanolic C. annuum L. extract
      (CAE) in a mouse model of ovalbumin-induced allergic airway inflammation. Animals
      were treated with CAE by oral gavage before ovalbumin challenge. After ovalbumin
      challenge, airway responsiveness to methacholine, influx of inflammatory cells
      into the lung, cytokine levels in bronchoalveolar lavage fluid and lung, nuclear
      factor-kappaB (NF-kappaB) activity in lungs, and lung histopathology were
      assessed. Oral treatment with CAE significantly reduced the pathophysiological
      signs of allergic airway disease, including increased inflammatory cell
      recruitment to the airways, airway hyperresponsiveness, and increased levels of T
      helper type 2 cytokines. Reactive oxygen species were also decreased in cells
      from bronchoalveolar lavage fluid. In addition, we found that administration of
      CAE attenuated ovalbumin-induced increases in NF-kappaB activity in lungs.
      Collectively, these results suggest that CAE may be an effective oral treatment
      for allergic airway inflammation by virtue of its antioxidant activity.

PMID- 21875364
TI  - Painful thyroiditis and subsequent atrophic hypothyroidism after cord blood
      transfusion.

PMID- 21875365
TI  - Imaging studies in sixty patients with acute suppurative thyroiditis.
AB  - BACKGROUND: Pyriform sinus fistulae are the major routes of infection in acute
      suppurative thyroiditis (AST). There have been only a few reports describing
      imaging studies in AST. We reviewed our imaging studies in patients with AST to
      elucidate its features so as to facilitate its diagnosis and treatment. METHODS:
      We reviewed ultrasonography (US) examinations, computed tomography (CT) scans,
      and barium swallow studies performed on 60 patients with the AST who were seen
      for medical care between 1998 and 2008 and were retrospectively reviewed. All of
      these patients had pyriform sinus fistulae. RESULTS: In the acute inflammatory
      stage, US showed a hypoechoic lesion spreading in and around the affected thyroid
      lobe, destruction of the lobe, and abscess formation in the neck. CT scans
      demonstrated similar features with clearer anatomical involvement and edema in
      the ipsilateral hypopharynx. These findings allowed easy diagnosis of AST.
      However, in the early inflammatory stage US showed an unclear hypoechoic area in
      the affected lobe and CT scans showed a nonspecific low-density area. These
      findings often led to erroneous diagnoses of subacute thyroiditis. A careful
      review of the US studies demonstrated that the following findings are
      characteristic of acute suppurative thyroidits: a perithyroidal hypoechoic space,
      effacement of the plane between the thyroid and perithyroid tissues, and the
      hypoechoic lesions being unifocal. The former two are not seen in subacute
      thyroiditis, and hypoechoic lesions in subacute thyroiditis are usually multiple
      and often bilateral. In the late inflammatory stage, US and CT scans often showed
      atrophy and an unclear hypoechoic or low-density area in and around the affected
      lobe. To detect pyriform sinus fistulae, barium swallow studies are more
      sensitive than US or CT scans. CONCLUSION: During the acute inflammatory stage of
      AST, both US and CT scans showed inflammatory processes in and around the
      affected thyroid lobe, although the CT scans more clearly demonstrate the
      anatomical locations involved. In the early inflammatory stage, these features
      may lead to an erroneous diagnosis of subacute thyroiditis. Careful US studies
      should indicate the correct diagnosis, which can then be proven by a barium
      swallow study or fine-needle aspiration followed by cytological examination and
      bacterial culturing.

PMID- 21875366
TI  - Cord blood thyroid tests in boys born with and without cryptorchidism:
      correlations with birth parameters and in utero xenobiotics exposure.
AB  - BACKGROUND: In utero exposure to environmental chemicals can result in
      reproductive toxicity via endocrine disruption mechanisms. Whether some of those
      contaminants also have an impact on fetal thyroid function or pathways, and,
      thus, potentially on neuropsychological development, is still debated. METHODS:
      We used samples from a cord blood (CB) and milk bank, established for a research
      on cryptorchidism and xenobiotic exposure to compounds known for their anti
      androgenic and/or estrogenic activity, to study CB thyroid tests and their
      correlation with CB and milk xenobiotics concentrations in boys born in Nice
      area. RESULTS: No difference was found in thyroid tests between 60 cryptorchid
      boys and 76 matched controls (median thyroid stimulating hormone 5.97 vs. 6.55
      mUI/L, free thyroxine [fT4] 13.1 vs. 12.9 pmol/L, free triiodothyronine [fT3] 1.9
      vs. 2.1 pmol/L), with no influence of season of birth, gestational age, maternal
      smoking, or mode of delivery (except for higher fT4 in control boys born
      vaginally). FT4 was correlated with fetal growth only in cryptorchid boys. Since
      we had previously shown differences between cryptorchid and controls exposure, we
      studied correlations of thyroid tests with xenobiotics in control boys only. All
      tested CB or maternal milk was contaminated by one or more selected xenobiotics,
      mainly polychlorinated biphenyls (PCBs), dichloro diphenyl dichloroethylene
      (DDE), dibutylphthalate, hexachlorobenzene, and bisphenol A. We found a
      significant negative correlation between fT4 and concentrations of PCB118, PC180,
      and DDE in milk (respectively r = -0.342, p < 0.03, r = -0.296, p = 0.031, r = 
      0.315, p = 0.016), persisting after adjustment for mode of delivery. There was a
      significant positive correlation of fT3 with milk concentrations of PCB138,
      PCB153, SigmaPCB, and dibutylphthalate (respectively r = 0.31, p = 0.016, r =
      0.28, p = 0.029; r = 0.34, p = 0.0079 and r = 0.272, p = 0.0295), with a trend
      for PCB180 (r = 0.259, p = 0.061). There was no correlation of thyroid
      stimulating hormone with any of the measured xenobiotics, except for a weak
      negative trend with CB bisphenol A (r = -0.25, p = 0.077). CONCLUSIONS: CB
      thyroid tests are within normal range in cryptorchid boys, similar to controls.
      Our data in controls suggest a possible weak correlation between in utero
      exposure to some xenobiotics (PCBs, DDE) and fT3 and fT4 CB concentrations, with
      usually negative correlations with fT4 and positive with fT3 concentrations,
      which we speculate could suggest an impact on deiodinases.

PMID- 21875367
TI  - Fluorodeoxyglucose positron emission tomography in primary thyroid lymphoma with
      coexisting lymphocytic thyroiditis.
AB  - BACKGROUND: Primary thyroid lymphoma is an uncommon neoplasm frequently
      associated with lymphocytic thyroiditis (LT). Once the pathologic diagnosis of
      primary thyroid lymphoma is established, imaging plays an important role in tumor
      staging and evaluating treatment response. The present case discusses the role of
      fluorodeoxyglucose positron emission tomography (18F-FDG PET)/computed tomography
      (CT) in this clinical setting along with the potential diagnostic challenges.
      PATIENT FINDINGS: A 44-year-old man with a history of LT and hypothyroidism
      presented with an enlarging goiter. Initial imaging evaluation showed markedly
      enlarged gland with bilateral cervical and mediastinal adenopathy.
      Histopathologic evaluation confirmed the diagnosis of primary thyroid lymphoma on
      a background of LT. An 18F-FDG PET/CT revealed increased uptake in the gland and
      lymph nodes. Follow-up 18F-FDG PET/CT after chemotherapy showed interval decrease
      in FDG uptake in the thyroid gland associated with interval decrease in the size
      and metabolic activity of the cervical and superior mediastinal lymph nodes.
      CONCLUSIONS: The frequent association of LT with primary thyroid lymphoma and the
      overlap of their clinical and pathologic findings pose a significant diagnostic
      challenge. While other imaging techniques are helpful in evaluating anatomic
      local and regional extent of primary thyroid lymphoma, 18F-FDG PET/CT can be of
      an added value in evaluating its metabolic activity and detecting regional and
      distant disease as well as in assessing response to treatment.

PMID- 21875371
TI  - Evidence of association between methylenetetrahydrofolate reductase gene and
      susceptibility to breast cancer: a candidate-gene association study in a South
      eastern European population.
AB  - The methylenetetrahydrofolate reductase (MTHFR) gene has been proposed as a
      candidate gene for breast cancer (BC). However, the specific role of MTHFR
      polymorphisms and haplotypes has not been fully clarified and replicated. We
      examined the association of two common MTHFR polymorphisms (C677T and A1298C) and
      their haplotypes in a candidate-gene association study, involving 300 female
      patients with BC and 283 healthy women. The single locus analysis for the two
      polymorphisms revealed an association only for the C677T polymorphism [odds ratio
      (95% confidence interval), OR=2.05 (1.21-3.48)], but adjustment for age
      diminished this association [OR=1.76 (0.92-3.42)]. The menopausal status showed
      no significant effect in the association between the MTHFR polymorphisms and BC.
      The analysis of haplotypes showed an association for the C677-A1298 haplotypes
      (p=0.04). The available evidence from our study may support a contributory role
      of MTHFR polymorphisms in BC development. Future larger studies may help in
      elucidating the genetics of BC further.

PMID- 21875370
TI  - Evaluation of DNA double strand breaks repair efficiency in head and neck cancer.
AB  - Head and neck cancers (head and neck squamous cell carcinomas [HNSCC]) are a
      heterogeneous group of neoplasms with varying presenting symptoms, treatment, and
      expected outcome. There is a need to find an effective way of its treatment at
      the molecular level. Thus, we should identify the mechanism of cancer cell
      response to damaging agents' activity, especially at DNA level. Our major goal
      was to evaluate the efficacy of DNA double strand breaks (DSBs) repair in HTB-43
      and SCC-25 cancer cell lines as well as lymphocytes taken from HNSCC patients and
      healthy donors. The DNA repair efficiency was measured by neutral comet assay as
      well as extrachromosomal assay for DNA DSBs repair (TAK assay). We determined the
      levels of two main pathways of DNA DSBs-nonhomologous end joining (NHEJ) and
      homologous recombination repair (HRR). Neutral comet assay was used for
      evaluation of DNA DSBs repair after treatment with genotoxic agents. DNA DSBs
      induced by gamma radiation were repaired slower in lymphocytes from HNSCC
      patients than in lymphocytes from healthy controls. HTB-43 and SCC-25 cancer cell
      lines have higher efficacy of NHEJ and HRR than lymphocytes taken from patients
      as well as control subjects. Our results confirm the necessity of further studies
      on the mechanisms of DNA DSBs repair to provide insight into the molecular basis
      of head and neck cancer, which will allow us to improve methods of HNSCC
      treatment.

PMID- 21875373
TI  - Total phenolic contents and free radical scavenging activities of different
      extracts of seabuckthorn (Hippophae rhamnoides) pomace without seeds.
AB  - In this study, 100% methanolic extract (ME), 70% aqua-methanolic extract (AME)
      and 100% aqueous extract of seabuckthorn byproduct were used to evaluate
      antioxidant activity. The total phenolic contents were high in AME (84.28 +/-
      1.58 mg of Gallic Acid Equivalent (GAE)/gm of extract) compared to other
      extracts. All the extracts scavenged different in vitro radicals in a
      concentration-dependent manner. The IC(50) values were lowest in AME for 2,2'
      azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt, 2,2-diphenyl-1
      picrylhydrazyl, superoxide and nitric oxide radicals, while ME had lowest values
      for hydroxyl radicals. The reducing power of the extracts increased in a dose
      dependent manner and was highest in AME. The findings of this study revealed that
      seabuckthorn pomace without seed is one of the important resources as an
      antioxidant for food, pharmaceuticals, cosmetic or nutraceutical industries.

PMID- 21875374
TI  - Highly selective and sensitive determination of free and total amino acids in
      Apocynum venetum L. (Luobuma tea) by a developed HPLC-FLD method coupled with pre
      column fluorescent labelling.
AB  - Amino acids (AA) are important chemical constituents of tea leaves remarkably
      influencing the quality of tea. In this study, free AA and total AA in Apocynum
      venetum L. (Luobuma tea) were estimated by HPLC equipped with fluorescent
      detector using 2-[2-(7H-dibenzo[a,g]carbazol-7-yl)-ethoxy] ethyl chloroformate
      (DBCEEC) as a fluorescent labelling reagent. Different parameters for
      derivatization and separation were optimized. AA were rapidly derivatized within
      3 min at room temperature with DBCEEC. In conjunction with a gradient elution, a
      baseline resolution of 20 analytes was achieved on a reversed-phase Hypersil BDS
      C18 column. LC separation for the derivatized AA showed good reproducibility.
      Twenty AA were detected and showed significant linear responses with correlation
      coefficients (>0.9992). This developed method offered the low detection limit of
      2.88-23.4 fmol.

PMID- 21875375
TI  - Study of polymorphisms in 4q27, 10p15, and 22q13 regions in autoantibodies
      stratified type 1 diabetes patients.
AB  - Type 1 diabetes (T1D) is a multifactorial disease mainly associated with the
      human leukocyte antigen region. Previous studies suggested the association of
      interleukin-2 (IL2) gene polymorphisms and its alpha- and beta-chain receptor
      (IL2RA and IL2RB) variants with different autoimmune diseases such as T1D, celiac
      disease, multiple sclerosis, and rheumatoid arthritis. All T1D studies were
      conducted in diabetic patients younger than 17 years at diagnosis. The aim of our
      study was to replicate these associations not only in pediatric patients, but
      also in individuals with late onset. We performed a genetic association study of
      chromosomal regions 4q27, 10p15, and 22q13 containing the IL2, IL2RA, and IL2RB
      genes in 445 T1D subjects and 828 healthy controls. Seven single nucleotide
      polymorphisms (SNPs) were selected, previously described as genetic factors
      related to several autoimmune diseases, and were analyzed by TaqMan assays. The
      reported association with T1D patients of the IL2RA-rs41295061 located in the
      10p15 region was replicated and our data suggest a trend of association of the
      polymorphisms IL2-rs17388568 and IL2-rs6822844 in 4q27. The effect of these
      markers was independent of the age at disease onset. Furthermore, the
      polymorphisms studied in 4q27 were not dependent on the presence of
      autoantibodies; however, the effect of the associated SNP in 10p15 (IL2RA
      rs41295061) was specific of patients sera positive for diabetes antibodies. In
      conclusion, our results seem to indicate that late-onset and young T1D patients
      share most genetic factors located in the studied regions, but some markers could
      correlate with the presence of T1D specific autoantibodies.

PMID- 21875376
TI  - Performance of the international classifications criteria for autoimmune
      hepatitis diagnosis in Mexican patients.
AB  - The revised score of the International Autoimmune Hepatitis Group (R-IAIHG) and
      the simplified criteria (SC) are used for diagnosis of autoimmune hepatitis
      (AIH). Our aim is to evaluate the performance of these classifications to
      differentiate AIH from other autoimmune liver diseases. The frequency of
      diagnosis of definite AIH was similar both by the R-IAIHG and the SC systems (41%
      versus 40%), whereas diagnosis of probable AIH was made more commonly by the R
      IAIHG than the SC (59% versus 29%), and 23 patients that have been graded as
      definite (n = 7) or probable (n = 16) AIH by the R-IAIHG had non-diagnostic
      scores by the SC system. The scoring systems rendered concordant diagnosis of
      definite (n = 15) and probable (n = 13) AIH in 28/73 patients (38%). Discordant
      diagnoses of AIH were rendered in 45/73 patients (62%). The R-IAIHG exhibited a
      sensitivity of 95%, specificity of 90%, and positive predictive value (PPV) and
      negative predictive value (NPV) of 93% for both. On the other hand, the SC had a
      lower sensitivity (65%) but a higher specificity (100%), PPV of 100%, and NPV of
      68%. In conclusion, both international scoring systems diagnosed the same number
      of cases as definite AIH. The R-IAIHG showed a higher sensitivity in diagnosing
      AIH, whereas the SC showed a higher specificity. SC are easier to apply at the
      bedside and exclude more patients that could have a different etiology.

PMID- 21875377
TI  - Distinctive autoantibody profile in Mexican Mestizo systemic sclerosis patients.
AB  - Systemic sclerosis (SSc) shows variable clinical expression among different
      ethnic groups. Herein, we describe the clinical features, prevalence of organ
      involvement, and autoantibody profile in Mexican Mestizo SSc patients and we
      compare them with patients from other ethnic groups.We included 139 SSc patients.
      They underwent clinical evaluation and were tested for antinuclear antibodies
      (ANA), anticentromere antibodies (ACA), anti-topoisomerase I, anti-RNA polymerase
      III, anti-U1 RNP, anti-U3 RNP, anti-U11/U12 RNP, anti-Th/To, anti-PM-Scl, anti
      Ku, antinucleosome, anti-double-stranded DNA (dsDNA), anti-Sm, anti-SSA, and anti
      SSB antibodies. Female predominance (93.5%) was noted; 56.8% of patients had
      limited cutaneous SSc; 91% had peripheral vascular involvement; 70% had joint
      involvement; 27% had musculoskeletal damage; 66% had gastrointestinal
      involvement; 41% had interstitial lung disease; 32% had pulmonary arterial
      hypertension (PAH); 11% had cardiac involvement; and in 1.4% renal involvement
      was observed. Our patients showed lower frequency of renal crisis and higher
      frequency of PAH than patients from other ethnic groups; also they showed higher
      frequency of ACA than Japanese and African American patients, higher frequency of
      anti-topoisomerase I than Caucasian and African American patients, higher
      frequency of anti-PM-Scl and anti-Ku and lower frequency of anti-RNA Pol III than
      the other ethnic groups. High frequencies of antinucleosome (41%) and anti-dsDNA
      (63%) were identified. SSc-specific autoantibody frequencies are different in our
      patients and in those from other ethnic groups; associations of autoantibodies
      with clinical manifestations are confirmed in our patients. Ethnicity and the
      interaction of gene and environmental factors may influence the clinical picture
      and autoantibody profile in SSc patients.

PMID- 21875378
TI  - Multiple sclerosis in Caucasians and Latino Americans.
AB  - Epidemiological and genetic studies suggest that the prevalence, median age of
      onset, and specific phenotypes of multiple sclerosis (MS) are different in
      Caucasians and Latino Americans. Recent epidemiological studies indicate an
      increase in MS prevalence in Latin America (LA), where the south-north gradient
      of latitude described for Nordic countries does not exist. Analysis of MS
      epidemiological and specific aspects in LA suggests that susceptibility and
      clinical behavior of the disease are related to mixtures and admixtures of genes
      in the population. MS is not present in Amerindians with Mongoloid genes, such as
      occurs in other pure ethnic groups. Surely, future studies will be carried out to
      obtain more reliable information. In this review, we contrast and analyze the
      available data of MS in LA and endemic countries.

PMID- 21875379
TI  - An experimental protocol for the fractionation and 2DE separation of HeLa and A
      253 cell lysates suitable for the identification of the individual antigenic
      proteome in Sjogren's syndrome.
AB  - Sjogren's syndrome (SS) is an autoimmune disease affecting exocrine glands,
      especially the salivary and lacrimal glands. Although most of the SS patients'
      sera have autoantibodies that can target a variety of antigens, it is not clear
      what determines which proteins will become autoantigens. The muscarinic receptor
      M3, an integral plasma membrane protein, has been proposed as a possible
      autoantigen in SS, and is endogenous in HeLa cells. The aim of this study was to
      develop a method that is able to separate and identify antigens recognised by
      sera from SS patients using lysates of HeLa and A-253 cells in 2D Western Blot
      (2DWB). The HeLa and A-253 cell lysates were fractionated in soluble and membrane
      bound proteins, and the membrane-bound proteins were enriched for integral
      proteins. The fractions were tested using WB, confirming the presence of the main
      cell compartments. The rehydration solution containing ASB-14 performed better
      than the others in all three steps (active rehydration, focus and transfer), and
      efficiently separated the muscarinic receptor M3. The M3 receptor was also
      detected in lysates from A-253 cells. The presence of this receptor in this cell
      line has not been proven earlier. This work develops a suitable protocol to
      perform a mapping of the autoantibodies present in the sera of single SS
      patients, using lysates from epithelial cell lines that represent the main cell
      compartments as an antigen source. It is our future aim to use this protocol to
      perform a mapping of the antibodies present in the sera of individual SS
      patients.

PMID- 21875380
TI  - Pregnancy outcomes in patients with systemic autoimmunity.
AB  - The impact of maternal systemic autoimmune diseases on pregnancy outcome is not
      unequivocally defined. We analysed the pregnancy outcome of 221 pregnancies from
      181 autoimmune patients, consecutively followed in a single Italian reference
      centre from 2001 to 2009. All patients were prospectively followed with monthly
      visits. Pregnancy outcome was compared with the previous obstetrical history. The
      patient population comprised five groups: primary antiphospholipid syndrome
      (PAPS, 39 pregnancies), antiphospholipid syndrome associated with a rheumatic
      disease (APS/RD, 17 pregnancies), other RD (92 pregnancies), isolated
      autoantibodies (autoAbs) in the absence of a definite autoimmune disease (aAbs,
      38 pregnancies) and reactive arthritis or spondyloarthropathies (35 pregnancies).
      Of these patients, 50.6% had previous pregnancy complications with an anamnestic
      live-birth rate of 43.4%. In these patients, complications dropped to 28.2%
      (44/156). This percentage was very similar to that observed in the 221
      pregnancies (29.9%, 66/221) with a live-birth rate of 87.3%. Mean neonatal weight
      was 3018 +/- 611 g; mean gestational age at delivery was 38.17 +/- 2.79 weeks.
      Thus, 10.4% of pregnancies resulted in preterm delivery and 10.9% newborns had
      low weight at delivery. APS/RD patients had the worse outcome: 17.6% resulted in
      miscarriage, 14.3% resulted in growth restriction and 50% resulted in preterm
      delivery. This result was mainly due to patients with APS/systemic lupus
      erythematosus (SLE) that had the lowest gestational age at delivery (30.8 +/-
      3.56 weeks) and the lowest newborn weight (1499 +/- 931 g). Results confirm that
      a strict follow-up and targeted treatments significantly improve pregnancy
      outcomes in autoimmune patients with PAPS, SLE and isolated autoAbs. The
      pregnancy outcome in patients with APS/SLE remains unsatisfactory.

PMID- 21875381
TI  - High potential to reverse the inhibition of myeloperoxidase by ceruloplasmin of
      anti-myeloperoxidase autoantibodies of IgG3 subclass.
AB  - Among the four subclasses, anti-neutrophil cytoplasmic antibodies (ANCAs) against
      myeloperoxidase (MPO) IgG, IgG3 subclass was associated with severe disease. This
      study aimed to investigate some aspects of the in vitro pathogenic potential of
      MPO-ANCA of IgG3 subclass. IgG from plasma of 10 consecutive patients with
      positive MPO-ANCA was divided into the IgG poor in IgG3 and the IgG rich in IgG3
      with protein A. Then, the ability to influence the oxidation activity of MPO, the
      ability to induce respiratory burst of neutrophils, and the ability to reverse
      the binding between ceruloplasmin (CP) and MPO were compared between the two
      fractions. The avidity of the MPO-ANCA-positive IgG rich in IgG3 was higher than
      that of the MPO-ANCA-positive IgG poor in IgG3 in 7 out of 10 patients. At the
      same antigen-binding level, the level of respiratory burst of neutrophils induced
      by the MPO-ANCA-positive IgG rich in IgG3 was significantly higher than that
      induced by the MPO-ANCA-positive IgG poor in IgG3 (1429.70 +/- 137.85 vs. 1321.70
      +/- 244.51, P = 0.049, expressed by the mean fluorescence intensity); the binding
      level between MPO and CP after adding the MPO-ANCA-positive IgG rich in IgG3 was
      significantly lower than after adding the MPO-ANCA-positive IgG poor in IgG3
      (0.599 +/- 0.214 vs. 0.777 +/- 0.353, P = 0.010, expressed by A 405); there was
      no significant difference in the MPO activity between adding the MPO-ANCA
      positive IgG poor in IgG3 and rich in IgG3 (P = 0.217). In conclusion, MPO-ANCA
      of IgG3 subclass might have stronger ability to reverse the inhibition of MPO by
      CP than other subclasses.

PMID- 21875382
TI  - Detection and characterization of ZnT8 autoantibodies could help to screen latent
      autoimmune diabetes in adult-onset patients with type 2 phenotype.
AB  - Autoantibodies to zinc transporter 8 (ZnT8A) constitute an additional marker of
      autoimmune diabetes, complementing those already used in diagnosis support. ZnT8A
      could also be found in latent autoimmune diabetes of adults (LADA). The aim of
      this study was to evaluate the prevalence of ZnT8A in adult-onset diabetic
      patients in Argentinian population. A total of 271 patients diagnosed for
      diabetes at mean age 53.4 +/- 10.9, body mass index <= 30, without insulin
      treatment for the first year of disease, and initially classified as type 2
      diabetic patients were tested for ZnT8A using cDNA plasmids encoding the C
      terminal domains (aa 268-369) carrying 325Arg, 325Trp, and a dimeric cDNA
      construct carrying both 325Arg and 325Trp (ZnT8 Arg-Trp325). We also analyzed
      proinsulin autoantibodies (PAA), glutamic acid decarboxylase autoantibodies
      (GADA), and protein tyrosine phosphatase IA-2 autoantibodies (IA-2A). A subset of
      101 patients was followed during 6 years in order to analyze insulin requirement.
      Out of the 271 patients, 22.1% presented at least one humoral marker, 2.6% were
      PAA+, 12.5% were GADA+, 3.3% were IA-2A+, and 10.7% were ZnT8A+. Among the
      latter, 7.0% were ZnT8A-Arg325, 51.7% were ZnT8A-Trp325, and 62.1% were ZnT8A-Arg
      Trp325. Furthermore, the prevalence of autoantibodies in the group of patients
      treated with insulin (n = 18) was 55.6%. These results demonstrated that a
      significant proportion of autoimmune adult-onset diabetic patients presented
      ZnT8A as the only humoral marker. Between them, the higher prevalence was for
      ZnT8A-Trp325. We suggest that screening for LADA patients, best performed with a
      minimal set of marker determination, must include at least the screening of GADA
      and ZnT8A-Arg-Trp325.

PMID- 21875383
TI  - Mechanisms of Hedgehog signalling in cancer.
AB  - The Hedgehog (Hh) pathway is a conserved signalling system essential for
      embryonic development and for the maintenance of self-renewal pathways in
      progenitor cells. Mutations that deregulate Hh signalling are directly implicated
      in basal cell carcinoma and medulloblastoma. The mechanisms of Hh pathway
      activation in cancers in which no pathway mutations have been identified are less
      clear, but of great translational significance. Small molecule inhibitors of the
      pathway, many of which are in early phase clinical trials, may shed further light
      on this question. Canonical Hh signalling promotes the expression of target genes
      through the Glioma-associated oncogene (GLI) transcription factors. There is now
      increasing evidence suggesting that 'non-canonical' Hh signalling mechanisms,
      some of which are independent of GLI-mediated transcription, may be important in
      cancer and development. The focus of this review is to summarise some of the
      known mechanisms of Hh signalling as well as its emerging role in cancer.

PMID- 21875384
TI  - Assessment of the nutritional status of children aged 5-12 years using upper arm
      composition.
AB  - BACKGROUND: Upper arm muscle area (UMA) and upper arm fat area (UFA) were
      introduced for assessment of child nutritional status. AIM: This cross-sectional
      study assesses child nutritional status using UMA and UFA. It also evaluates the
      suitability of upper arm muscle area by height (UAMAH) for assessing child under
      nutrition with respect to stunting and wasting. SUBJECTS AND METHODS: The study
      was conducted among 1248 children (619 boys; 629 girls) aged 5-12 years belonging
      to the Bengalee Muslim Population of West Bengal, India. Anthropometric
      measurements of height, weight, mid-upper arm circumference and triceps skin-fold
      were recorded. Nutritional status was assessed using UMA, UFA and UAMAH.
      Percentile curves were derived using the least median square method. RESULTS:
      Mean age specific values of UMA, UFA and UAMAH of boys and girls were markedly
      below the 5th percentile. Using UAMAH, a very high proportion of children (boys,
      91.28%; girls, 88.55%) were found to be under-nourished. Prevalence of stunting
      (boys, 39.74%; girls, 41.49%) and wasting (boys, 19.55%; girls, 15.74%) were also
      found to be high. CONCLUSION: The combination of UMA, UFA, UAMAH and conventional
      nutritional indices appear to be useful for assessment of child under-nutrition.

PMID- 21875385
TI  - Silibinin induced-autophagic and apoptotic death is associated with an increase
      in reactive oxygen and nitrogen species in HeLa cells.
AB  - Silibinin, as the major active constituent of silymarin, has its various
      biological effects. Here, we investigated the inhibitory effects of silibinin on
      HeLa cell growth in relation to autophagy and apoptosis induced by reactive
      oxygen species (ROS) and reactive nitrogen species (RNS) generation. Silibinin
      dose and time-dependently decreased cell growth cultured in medium containing 10%
      fetal bovine serum or in serum free media (SFM) with an IC(50) of approximately
      80-100 and 40-60 MUM at 24 h, respectively. Silibinin induced autophagy at 12 h,
      confirmed by monodansylcadervarine (MDC) staining and up-regulation of beclin-1,
      and induced apoptosis at 24 h, detected by observation of apoptotic bodies and
      activation of caspase-3. 3-methyladenine (3-MA) inhibited silibinin-induced
      autophagy and attenuated the silibinin's inhibitory effect on cell viability,
      suggesting that autophagy enhanced silibinin-induced cell death. Silibinin
      increased ROS levels at 12 h, and ROS scavenger, N-acetylcysteine (NAC),
      significantly reversed the cytotoxicity of silibinin through inhibiting both
      autophagy and apoptosis. Specific antioxidants were applied and results indicated
      that hydroxyl radical (.OH) was the major ROS induced by silibinin, and OH
      scavenger glutathione (GSH) inhibited apoptosis and autophagy. Silibinin also
      generated RNS production in the cells at 12 h. High concentration of N omega
      nitro-l-arginine methyl ester (L-NAME) as nitric oxide synthase (NOS) inhibitor
      attenuated the cytotoxicity of silibinin by decreasing ROS levels, leading to
      down-regulation of apoptosis. Silibinin also could interrupt the respiring
      functions of mitochondria, leading to ROS production and oxidative damage.

PMID- 21875386
TI  - Parent strategies for addressing the needs of their newly adopted child.
AB  - The purpose of this study was to describe reflections of nine American parents on
      the strengths, challenges, and strategies in parenting young children newly
      adopted from another country. Eight mothers and one father with an adopted child
      aged <3 years and home for <3 months completed standardized assessments measuring
      the child's social emotional development, sensory processing, and parental
      stress. Each parent participated in qualitative interview to discuss challenges
      and strategies helpful in addressing their children's needs. All parents reported
      challenges addressing their child's needs in the areas of sleep, feeding,
      attachment and self-regulation, and soothing. Parents reported similar strategies
      to address their child's behavioral concerns. Parents also reported on family
      factors and community resources that supported the success of the adoption.
      Although many families described their adoptive child as having challenges with
      multiple daily life activities, parents reported being able to create effective
      strategies to address many of these challenging behaviors.

PMID- 21875387
TI  - Early endoscopy or CT in caustic injuries: a re-evaluation of clinical practice.

PMID- 21875388
TI  - Carbon monoxide poisoning caused by water pipe smoking.

PMID- 21875389
TI  - Automatic intelligibility assessment of pathologic speech over the telephone.
AB  - Objective assessment of intelligibility on the telephone is desirable for voice
      and speech assessment and rehabilitation. A total of 82 patients after partial
      laryngectomy read a standardized text which was synchronously recorded by a
      headset and via telephone. Five experienced raters assessed intelligibility
      perceptually on a five-point scale. Objective evaluation was performed by support
      vector regression on the word accuracy (WA) and word correctness (WR) of a speech
      recognition system, and a set of prosodic features. WA and WR alone exhibited
      correlations to human evaluation between |r| = 0.57 and |r| = 0.75. The
      correlation was r = 0.79 for headset and r = 0.86 for telephone recordings when
      prosodic features and WR were combined. The best feature subset was optimal for
      both signal qualities. It consists of WR, the average duration of the silent
      pauses before a word, the standard deviation of the fundamental frequency on the
      entire sample, the standard deviation of jitter, and the ratio of the durations
      of the voiced sections and the entire recording.

PMID- 21875391
TI  - Mild thyroid hormone excess is associated with a decreased physical function in
      elderly men.
AB  - INTRODUCTION: In the adult, subclinical hyperthyroidism (Shyper) may alter
      skeletal muscle mass and strength. However, whether these effects are present in
      elderly subjects is not known. We explored the relationship between mild
      hyperthyroidism and physical function in a population-based sample of older
      persons. METHODS: In a cross-sectional analysis, calf muscle cross-sectional area
      (CMA), handgrip strength, nerve conduction velocity (NCV), and Short Physical
      Performance Battery (SPPB) scores were compared between 364 euthyroid (Eut) and
      28 Shyper men as well as between 502 Eut and 39 Shyper women. In a longitudinal
      analysis, we evaluated the relationship between baseline plasma TSH, FT3 and FT4
      and the 3-year change in SPPB score in 304 men and 409 women who were euthyroid
      at enrolment. RESULTS: At the cross-sectional analysis, Shyper men, but not
      women, had a significantly (p = 0.02) lower SPPB score than Eut controls,
      although with comparable CMA, grip strength and NCV, and were more likely to have
      poor physical performance (odds ratio = 2.97, p < 0.05). Longitudinal analysis
      showed that in Eut men higher baseline FT4 was significantly (p = 0.02)
      predictive of a lower SPPB score at the 3-year follow-up. CONCLUSION: Even a
      modest thyroid hormone excess is associated with a reduced physical function in
      elderly men.

PMID- 21875393
TI  - Combination of cellular population data and CytoDiff analyses for the diagnosis
      of lymphocytosis.
AB  - BACKGROUND: Differentials with moderate lymphocytosis are common in hematology
      laboratories and it is important in these cases to discriminate monoclonal from
      reactive lymphocytosis (RL). Blood smear reflex examination is dependent of the
      expertise of a cytologist, time-consuming and not always informative. Therefore,
      rapid and easy orientation parameters are clearly needed to discriminate
      malignant from RL. METHODS: The differential performed by the Beckman-Coulter
      analyzers is based on the determination of three parameters (volume, conductivity
      and scatter of the cell subpopulations) called cellular population data (CPD).
      This study evaluated CPD in 332 patients with a typical B-chronic lymphocytic
      leukemia (B-CLL), 90 patients with other B-lymphoproliferative diseases (OLPD)
      and 55 patients with a proven RL, and established a discriminating protocol to
      identify these pathologies. Secondly, this approach was evaluated in a
      prospective study including 102 patients with lymphocyte counts above 3.5 *
      10(9)/L and in each case the diagnosis suggested by CPD was compared with
      conventional flow cytometry (FC) analysis and that obtained using CytoDiff
      reagent, a combination of six antibodies/five colors which performs a rapid WBC
      differential by FC. RESULTS: Lymphocyte anisocytosis was observed for malignant
      and RL. A low lymphocyte volume identifies monoclonal B-cell lymphocytosis and
      classical B-CLL. CytoDiff analysis is helpful when lymphocyte volume is in the
      normal range. A ratio B-Ly/total Ly count >0.32 is suggestive of a B-malignancy,
      whereas a non-cytotoxic T-lymphocyte count above 2.43 * 10(9)/L suggests RL.
      CONCLUSIONS: The analysis of CPD in combination with CytoDiff analysis shows
      promise for the rapid and accurate identification of lymphocyte pathologies in
      routine practice.

PMID- 21875392
TI  - An osteochondral culture model to study mechanisms involved in articular
      cartilage repair.
AB  - Although several treatments for cartilage repair have been developed and used in
      clinical practice the last 20 years, little is known about the mechanisms that
      are involved in the formation of repair tissue after these treatments. Often,
      these treatments result in the formation of fibrocartilaginous tissue rather than
      normal articular cartilage. Because the repair tissue is inferior to articular
      cartilage in terms of mechanical properties and zonal organization of the
      extracellular matrix, complaints of the patient may return. The biological and
      functional outcome of these treatments should thus be improved. For this purpose,
      an in vitro model allowing investigation of the involved repair mechanisms can be
      of great value. We present the development of such a model. We used bovine
      osteochondral biopsies and created a system in which cartilage defects of
      different depths can be studied. First, our biopsy model was characterized
      extensively: we studied the viability by means of lactate dehydrogenase (LDH)
      excretion over time and we investigated expression of cartilage-related genes in
      osteochondral biopsies and compared it with conventional cartilage-only explants.
      After 28 days of culture, LDH was detected at low levels and mRNA could be
      retrieved. The expression of cartilage-related genes decreased over time. This
      was more evident in cartilage-only explants, indicating that the biopsy model
      provided a more stable environment. We also characterized the subchondral bone:
      osteoclasts and osteoblasts were active after 28 days of culture, which was
      indicated by tartrate acid phosphatase staining and alkaline phosphatase
      measurements, respectively, and matrix deposition during culture was visualized
      using calcein labeling. Second, the applicability of the model was further
      studied by testing two distinct settings: (1) implantation of chondrocytes in
      defects of different depths; (2) two different seeding strategies of
      chondrocytes. Differences were observed in terms of volume and integration of
      newly formed tissue in both settings, suggesting that our model can be used to
      model distinct conditions or even to mimic clinical treatments. After extensive
      characterization and testing of our model, we present a representative and
      reproducible in vitro model that can be used to evaluate new cartilage repair
      treatments and study mechanisms in a controlled and standardized environment.

PMID- 21875394
TI  - Rapid and simple IgG specific test for the exclusion of heparin induced
      thrombocytopenia (HIT).
AB  - BACKGROUND: The exclusion of heparin induced thrombocytopenia (HIT) is required
      for selecting the most appropriate anticoagulation therapy in affected patients.
      It requires the combination of clinical data with the detection of antibodies
      directed against platelet factor 4 (PF4) in complex with polyanions (PA) such as
      heparin. METHODS: We developed a lateral flow immunoassay (LFIA) for PF4/PA
      complex specific IgG antibodies based on gold nanoparticles. Unlike most other
      assays, the initial immune reaction takes place in the liquid phase. The
      sensitivity of the assay has been adjusted with clinical samples aiming in the
      reliable detection of sera which are positive in a functional platelet activation
      assay. RESULTS: Sera from 60 patients with suspected HIT were investigated. LFIA
      identified correctly all samples (n=20) which were positive in a functional assay
      (HIPA) and an IgG specific ELISA. It correlated with ELISA, but false positive
      results were less frequent (7 samples were negative with LFIA and HIPA but
      positive with ELISA). CONCLUSIONS: The LFIA may be a suitable tool for the rapid
      exclusion of HIT within 10 min.

PMID- 21875395
TI  - Iron deficiency prevalence is increased among Helicobacter pylori infected
      Brazilian patients.

PMID- 21875396
TI  - Multiplex protein assay performance/evaluation and the requirement for precision
      and correlation to clinical assays.

PMID- 21875397
TI  - Uptake of cobalamin and markers of cobalamin status: a longitudinal study of
      healthy pregnant women.
AB  - BACKGROUND: Currently, it is unknown whether the decline in plasma cobalamin
      observed during pregnancy is caused by malabsorption of the vitamin. This study
      examined cobalamin absorption and markers of cobalamin status during normal
      pregnancy. METHODS: Twenty-seven pregnant Danish women were examined at gestation
      weeks 13, 24 and 36. The absorption test CobaSorb was performed in all women
      implying measurement of holotranscobalamin or cyanocobalamin bound to
      transcobalamin before and after 2 days intake of 3 * 9 MUg cobalamin. Serum
      cobalamin and the two cobalamin binding proteins transcobalamin and haptocorrin,
      including haptocorrin saturated with cobalamin or analogues, were measured, and
      so was plasma methylmalonic acid and homocysteine. RESULTS: No change in the
      uptake of cobalamin was observed throughout pregnancy. Serum cobalamin displayed
      a gradual decline during pregnancy (p<0.0001), while holotranscobalamin remained
      unchanged, despite an increase in total transcobalamin (p<0.0001). In accord with
      these results, total haptocorrin showed a decline from the 1st to 3rd trimester
      (p=0.007) and cobalamin bound to haptocorrin declined (p<0.0001). Interestingly,
      the amount of cobalamin analogues attached to haptocorrin remained unchanged.
      Methylmalonic acid (p=0.002) and homocysteine (p<0.0001) increased during
      pregnancy. CONCLUSIONS: Cobalamin absorption remains unchanged during normal
      pregnancy, as judged by the CobaSorb test. No change was observed in the
      biological active holotranscobalamin during pregnancy. Thus, the pregnancy
      related decline in cobalamin is caused by alternations in haptocorrin-bound
      cobalamin. Surprisingly, no pregnancy-related change was observed in the amount
      of analogues attached to haptocorrin.

PMID- 21875398
TI  - Status of serum-calcium and -albumin measurement in Argentina assessed in 300
      representative laboratories with 20 fresh frozen single donation sera.
AB  - BACKGROUND: The Fundacion Bioquimica Argentina (FBA) performs external quality
      assessment (EQA) of >3200 laboratories. However, FBA realizes that sample non
      commutability and predominant use of heterogeneous systems may bias the estimated
      performance and standardization status. To eliminate these confounding factors, a
      study using frozen single donation sera was undertaken with the focus on serum
      calcium and -albumin measurement. METHODS: Target values were established from
      the results produced with homogeneous systems. In groups of n=7, system effects
      were investigated. Laboratory performance was evaluated from the correlation
      coefficient r between the measurement results for all sera and the target values.
      This allowed ranking of the laboratories and judgment of the deviation for
      individual samples (total error) against a 10% limit. The total error
      specification was a deviation for >= 5 samples exceeding 10% and/or causing a
      result outside the laboratory's reference interval. RESULTS: For calcium (n=303)
      (range: 2.06-2.42 mmol/L), 81 laboratories had an r-value <0.6, 43 even <0.4; the
      total error was relevant for 97 (10% limit) and 111 (reference interval)
      laboratories. For albumin (n=311) (range: 34.7-45.7 g/L) r was <0.7 (<0.4) in 44
      (16) laboratories; 83 and 36 laboratories exceeded the total error criteria.
      Laboratories using homogeneous systems were generally ranked higher by
      correlation. System effects were moderate for calcium, but significant for
      albumin. CONCLUSIONS: The study demonstrated the need to improve the quality and
      harmonization of calcium and albumin testing in the investigated laboratories. To
      achieve this objective, we promote co-operation between laboratories, EQA
      provider and manufacturers.

PMID- 21875399
TI  - Regulation of in vitro diagnostics (IVDs) for use in clinical diagnostic
      laboratories: towards the light or dark in clinical laboratory testing?
AB  - A revised framework for the regulation of in vitro diagnostic devices (IVDs) came
      into force in Australia on July 1, 2010 that aims to 'ensure that public and
      personal health are adequately protected', but which instead may lead to adverse
      outcomes in clinical diagnosis and management. The regulatory process aims to
      regulate all IVDs, including those used by clinical diagnostic laboratories,
      which are already subject to scrutiny as part of the current laboratory
      accreditation process. The IVD regulatory process initiated in Australia is
      similar to that used in Canada, but different to that currently operating in the
      USA and Europe. However, it is feasible that other countries will in time adopt a
      similar regulatory framework, given that many countries are involved in the
      development process. In this opinion paper, the regulatory process for IVDs
      across several geographies are outlined, as are some benefits and weaknesses of
      the new regulatory process now applied to Australia, as potentially planned for
      other regions of the world.

PMID- 21875400
TI  - The Greek way to the Register: the establishment and operation of the Register
      for Clinical Chemists-Clinical Biochemists in Greece.
AB  - In Greece, there is no officially organized training in clinical chemistry for
      scientists. The Greek Society of Clinical Chemistry-Clinical Biochemistry (GSCC
      CB), following the encouragement of the EC4/RC decided to organize a voluntary
      Register for specialists in clinical chemistry. The following criteria for
      registration were defined: 1) University degree in Chemistry, Biochemistry,
      Biology, Medicine, Pharmacy or other relevant subject. 2) A total of 9 years of
      university studies and postgraduate specialization in clinical chemistry-clinical
      biochemistry. 3) A minimum of 4 years of postgraduate specialization in clinical
      chemistry-clinical biochemistry on the job. 4) The candidate must be practicing
      clinical chemistry-clinical biochemistry in a laboratory in a medical environment
      in Greece. The postgraduate specialization in clinical chemistry-clinical
      biochemistry includes the laboratory training and the theoretical education. The
      laboratory training is organized by the GSCC-CB according to the Professional
      Training Dossier. The theoretical education was organized in a series of 18
      "Seminars" which was the content of the "Educational program" of the GSCC-CB.
      Successful completion of the Educational program leads to a Certificate of
      Competence. The Greek Register has gained equivalence with the EC4 Register and
      it has 218 members, more than 80 of whom are European clinical chemists.

PMID- 21875401
TI  - Human papilloma virus (HPV) molecular diagnostics.
AB  - Human Papilloma Virus (HPV) is becoming a menace worldwide, especially to the
      developing world, due to its involvement in a variety of malignancies, with
      cervical cancer being the most important and prevalent. There are many HPV types;
      HPV 16/18 are the most carcinogenic but few others are also characterized as high
      risk (HR). They can cause a variety of low- or high-grade cellular abnormalities,
      most frequently detected in a routine Pap test. Most infections clear within 2
      years, however, a minority persists and potentially could progress to cervical
      cancer. Molecular tests detecting HPV DNA, RNA or proteins are now being
      available either commercially or in-house developed. DNA detection is nowadays an
      established tool for diagnosis and monitoring of HPV-related disease, however,
      there is lack of a reference method and standardization with reference materials.
      The various available test formats create confusion on which molecular test to
      choose and what are its limitations. Therefore, the need for lab accreditation
      and participation in proficiency testing has to be stressed. Novel HPV biomarkers
      (RNA, protein etc.) are now intensively examined for their inclusion as adjunct
      tools. Recently, developed prophylactic vaccines for HPV 16/18 have already
      proven safe and efficient and raise high expectations for the complete
      eradication of these types in the future.

PMID- 21875402
TI  - Purification of the proprotein convertase furin by affinity chromatography based
      on PC-specific inhibitors.
AB  - In eucaryotes, many secreted proteins and peptides are proteolytically excised
      from larger precursor proteins by a specific class of serine proteases, the
      proprotein/prohormone convertases (PCs). This cleavage is essential for substrate
      activation, making the PCs very interesting pharmacological targets in cancer and
      infectious disease research. Correspondingly, their structure, function and
      inhibition are intensely studied - studies that require the respective target
      proteins in large amounts and at high purity. Here we describe the development of
      a novel purification protocol of furin, the best-studied member of the PC family.
      We combined the heterologous expression of furin from CHO cells with a novel
      purification scheme employing an affinity step that efficiently extracts only
      active furin from the conditioned medium by using furin-specific inhibitor
      moieties as bait. Several potential affinity tags were synthesized and their
      binding to furin characterized. The best compound, Biotin-(Adoa)(2)-Arg-Pro-Arg-4
      Amba coupled to streptavidin-Sepharose beads, was used in a three-step
      chromatographic protocol and routinely resulted in a high yield of a homogeneous
      furin preparation with a specific activity of ~60 units/mg protein. This
      purification and the general strategy can easily be adapted to the efficient
      purification of other PC family members.

PMID- 21875403
TI  - Dose accuracy and durability of a durable insulin pen before and after simulated
      lifetime use.
AB  - BACKGROUND AND OBJECTIVE: NovoPen Echo* is an insulin pen designed specifically
      for children and adolescents with diabetes. The pen combines half-unit dosing and
      a simple memory function that records the size of the last dose and the time in
      hours that has elapsed since last injection. Durability is an essential feature
      of durable insulin pens in order to ensure accuracy throughout the lifetime of
      the pen. This study was designed to assess dose accuracy and durability of
      NovoPen Echo before and after simulated lifetime use. RESEARCH DESIGN AND
      METHODS: All testing was conducted according to International Organization for
      Standardization (ISO) guideline 11608-1 for pen injectors. Dose accuracy was
      measured for the delivery of 0.5 international units** (IU) (5 mg), 15 IU (150
      mg) and 30 IU (300 mg) test medium before and after lifetime simulation under
      standard, cool and hot conditions. Functionality tests were also performed under
      a number of stress conditions including dry heat, cyclical temperature,
      vibration, free fall and electrostatic discharge. RESULTS: The dose accuracy of
      NovoPen Echo meets the requirement stated in ISO 11608-1 for all three doses for
      all tests before and after lifetime simulation. The pens remained intact and
      retained dosing accuracy at all doses after exposure to variations in temperature
      and humidity and before and after physical challenge to simulate lifetime use.
      CONCLUSIONS: The accuracy of NovoPen Echo was retained under conditions of stress
      likely to be encountered in everyday use due to its durable design.

PMID- 21875404
TI  - Trends in nanotechnology patents applied to the health sector.
AB  - The aim of the article is to present a method for identifying trends in patent
      applications for nanotechnology applied to the health sector around the world,
      based on the International Patent Classification. This classification divides the
      sector into: dental care, drugs, diagnostic kits, and medical apparatus & medical
      care. The Derwent database was mined for patent documents using nanotechnology
      terms associated with the IPC subclasses from the health subsectors. The number
      of patents was found to be rising, led by the United States, particularly
      universities and R centers. In the dental care subsector, nanotechnology was
      found to be used in composite material for manufacturing dental appliances. In
      drugs, the focus is on the use of nanoparticulate compositions comprising agents
      that are useful for a variety of diseases. In diagnostic kits, nanostructures
      have been patented that are capable of detecting target analytes. Meanwhile, in
      medical apparatus & medical care, patent applications have been made for
      nanocapsules and/or nanocomposite materials inserted in devices and guide
      catheters. A study was also made of patents in Brazil, where the same assignees
      and the same country (United States) as in the survey of global patents were
      found to be the leading patent applicants / holders.

PMID- 21875405
TI  - Review of cellulose nanocrystals patents: preparation, composites and general
      applications.
AB  - This review attempts to visualize the actual impact of nanocellulose-based
      materials in different areas. A detailed search in recent patent databases on
      nanocellulose showed the importance of this material, as well as relevant topics
      concerning its technological preparations to obtain versatile new composites
      materials, and the applications of nanocellulose in different domains. At the
      present moment, the most common techniques for nanocellulose preparation were
      found to be acid and enzymatic procedures, oxidation, electrospinning, high
      pressure homogenization, and steam explosion processes. Concerning nanocellulose
      composites, several aspects were found in recent patents ranging from simple to
      complex structures with different properties. As unique materials, nanocellulose
      can be used in different areas of expertise, such as in biomedical and technical
      applications. This review is a useful tool for researchers to provide an update
      on nanocellulose patents in an expanding and interesting field of nanotechnology.

PMID- 21875406
TI  - Slot optical waveguide usage in forming passive optical devices.
AB  - We have reviewed the work on SOI slot optical waveguides followed by our work. In
      a slot waveguide structure, light can be confined in a low index slot guarded by
      high index slabs. Slot structures are being used in forming complex structures;
      such as ring resonator circuits. The increased round trip in ring resonator
      circuits signifies the importance of dispersion calculations. We did analytical
      and numerical investigations of slot structures' dispersion characteristics. Our
      dispersion tuned slot structures can help in reducing the dispersion effects on
      optical signal, which will in turn improve the efficiency of light-on-chip
      circuits. Since the advent of slot optical waveguides, SOI based slot optical
      waveguides have been under consideration. It has been found that glass based slot
      optical waveguide structures with relatively low refractive index contrast ratio
      can also play an important role in forming complex nano-size optical devices. We
      made use of power confined inside low index slot regions for a double slot
      structure. Opto-mechanical sensors have been proposed based upon: (a) variation
      in power confined inside low index slot region due to the movement of central
      high index slab under the action of external force (temperature, pressure,
      humidity, etc). vide Chinese Patent No. ZL 200710176770.1, 2007 (b) variation in
      power confined inside low refractive index slot regions due to movement of both
      slots under the action of external force (temperature, pressure, humidity, etc).

PMID- 21875408
TI  - Optimized turmeric extract reduces beta-Amyloid and phosphorylated Tau protein
      burden in Alzheimer's transgenic mice.
AB  - In a previous in vitro study, the standardized turmeric extract, HSS-888, showed
      strong inhibition of Abeta aggregation and secretion in vitro, indicating that
      HSS-888 might be therapeutically important. Therefore, in the present study, HSS
      888 was evaluated in vivo using transgenic 'Alzheimer' mice (Tg2576) over
      expressing Abeta protein. Following a six-month prevention period where mice
      received extract HSS-888 (5mg/mouse/day), tetrahydrocurcumin (THC) or a control
      through ingestion of customized animal feed pellets (0.1% w/w treatment), HSS-888
      significantly reduced brain levels of soluble (~40%) and insoluble (~20%) Abeta
      as well as phosphorylated Tau protein (~80%). In addition, primary cultures of
      microglia from these mice showed increased expression of the cytokines IL-4 and
      IL-2. In contrast, THC treatment only weakly reduced phosphorylated Tau protein
      and failed to significantly alter plaque burden and cytokine expression. The
      findings reveal that the optimized turmeric extract HSS-888 represents an
      important step in botanical based therapies for Alzheimer's disease by inhibiting
      or improving plaque burden, Tau phosphorylation, and microglial inflammation
      leading to neuronal toxicity.

PMID- 21875407
TI  - N-methyl D-aspartate (NMDA) receptor antagonists and memantine treatment for
      Alzheimer's disease, vascular dementia and Parkinson's disease.
AB  - Memantine, a partial antagonist of N-methyl-D-aspartate receptor (NMDAR),
      approved for moderate to severe Alzheimer's disease (AD) treatment within the
      U.S. and Europe under brand name Namenda (Forest), Axura and Akatinol (Merz), and
      Ebixa and Abixa (Lundbeck), may have potential in alleviating additional
      neurological conditions, such as vascular dementia (VD) and Parkinson's disease
      (PD). In various animal models, memantine has been reported to be a
      neuroprotective agent that positively impacts both neurodegenerative and vascular
      processes. While excessive levels of glutamate result in neurotoxicity, in part
      through the over-activation of NMDARs, memantine-as a partial NMDAR antagonist,
      blocks the NMDA glutamate receptors to normalize the glutamatergic system and
      ameliorate cognitive and memory deficits. The key to memantine's therapeutic
      action lies in its uncompetitive binding to the NMDAR through which low affinity
      and rapid off-rate kinetics of memantine at the level of the NMDAR-channel
      preserves the physiological function of the receptor, underpinning memantine's
      tolerability and low adverse event profile. As the biochemical pathways evoked by
      NMDAR antagonism also play a role in PD and since no other drug is sufficiently
      effective to substitute for the first-line treatment of L-dopa despite its side
      effects, memantine may be useful in PD treatment with possibly fewer side
      effects. In spite of the relative modest nature of its adverse effects, memantine
      has been shown to provide only a moderate decrease in clinical deterioration in
      AD and VD, and hence efforts are being undertaken in the design of new and more
      potent memantine-based drugs to hopefully provide greater efficacy.

PMID- 21875409
TI  - Matrix metalloproteinase-2 and epidermal growth factor are decreased in platelets
      of Alzheimer patients.
AB  - Alzheimer's disease (AD) is the most prevalent type of dementia. Despite
      considerable advances in diagnostic accuracy, diagnostic procedures that are
      easily accessible are still sorely needed. Blood biomarkers are therefore in the
      focus of research. Platelets contain a high concentration of the amyloid
      precursor protein (APP), which has been mentioned as a potentially useful
      diagnostic marker. The aim of the present study was to analyze various cell
      adhesion molecules (CAMs), cytokines, growth factors, and matrix
      metalloproteinases (MMPs) in platelets of AD and mild cognitively impaired (MCI)
      patients as compared to healthy controls. Our data show a significant decrease in
      the levels of epidermal growth factor (EGF) and of MMP-2 in platelets of AD
      patients and decreased levels of MMP-2 in MCI. The APP ratio was slightly but not
      significantly decreased in AD patients, whereas CD40L and serotonin were
      unchanged. Our findings demonstrate specific changes in AD platelets. Whether
      these biomarkers can be established as potential early diagnostic biomarkers for
      AD remains to be established in longitudinal studies.

PMID- 21875410
TI  - Influence of lithium treatment on GDNF serum and CSF concentrations in patients
      with early Alzheimer's disease.
AB  - Preclinical and clinical studies gave evidence that lithium could be useful in
      the treatment of Alzheimer's disease (AD). One possible mechanism of action might
      be the induction of neurotrophins. Recently, we found a significant increase of
      brain-derived neurotrophic factor (BDNF) serum levels in AD patients treated with
      lithium and a significant decrease of ADAS Cog sum scores in comparison to
      placebo-treated patients. In another previous study we have shown that glial cell
      line-derived neurotrophic factor (GDNF) levels in CSF of patients with early AD
      are increased most probably due to an upregulated expression in CNS as an
      adaptive process of the impaired brain to enhance neurotrophic support at least
      in early stages of disease. Here we assessed the influence of a lithium treatment
      on GDNF serum and cerebrospinal fluid (CSF) concentrations in a subset of a
      greater sample recruited for a randomized, single-blinded, placebo-controlled,
      parallel-group multicenter 10-week study, investigating the efficacy of lithium
      treatment in AD patients. We found a significant negative correlation of lithium
      concentration in serum with GDNF concentration in CSF at the end of treatment (r
      = -0.585, p = 0.036) and with the difference of GDNF concentration in CSF before
      and after treatment (r = - 0.755, p = 0.003). However, we could not show a
      difference in GDNF concentrations between the patients after the treatment with
      lithium or placebo (serum, mean +/- standard deviation: 434.3 +/- 117.9 pg/ml
      versus 543.8 +/- 250.0 pg/ml, p = 0.178; CSF, 62.3 +/- 37.4 pg/ml versus 72.8 +/-
      43.9 pg/ml, p = 0.511). The findings of the present investigation indicated that
      beneficial effects of the lithium treatment might reduce the necessity of
      enhanced GDNF expression in the CNS in early AD.

PMID- 21875411
TI  - Dogs with cognitive dysfunction syndrome: a natural model of Alzheimer's disease.
AB  - In the search for appropriate models for Alzheimer's disease (AD) involving
      animals other than rodents, several laboratories are working with animals that
      naturally develop cognitive dysfunction. Among the animals tested, dogs are quite
      unique in helping to elucidate the cascade of events that take place in brain
      amyloid-beta (Abeta)deposition aging, and cognitive deficit. Recent innovative
      research has validated human methods and tools for the analysis of canine
      neuropathology and has allowed the development of two different approaches to
      investigate dogs as natural models of AD. The first approach relates AD-like
      neuropathy with the decline in memory and learning ability in aged housed dogs in
      a highly controlled laboratory environment. The second approach involves research
      in family-owned animals with cognitive dysfunction syndrome. In this review, we
      compare the strengths and limitations of housed and family-owned canine models,
      and appraise their usefulness for deciphering the early mechanisms of AD and
      developing innovative therapies.

PMID- 21875412
TI  - Metric distances between hippocampal shapes indicate different rates of change
      over time in nondemented and demented subjects.
AB  - In this article, we use longitudinal morphometry (shape and size) measures of
      hippocampus in subjects with mild dementia of Alzheimer type (DAT) and
      nondemented controls in logistic discrimination. The morphometric measures we use
      are volume and metric distance measures at baseline and follow-up (two years
      apart from baseline). Morphometric differences with respect to a template
      hippocampus were measured by the metric distance obtained from the large
      deformation diffeomorphic metric mapping (LDDMM) algorithm. LDDMM assigns metric
      distances on the space of anatomical images, thereby allowing for the direct
      comparison and quantization of morphometric changes. We also apply principal
      component analysis (PCA) on volume and metric distance measures to obtain
      principal components that capture some salient aspect of morphometry. We
      construct classifiers based on logistic regression to distinguish diseased and
      healthy hippocampi (hence potentially diagnose the mild form of DAT). We consider
      logistic classifiers based on volume and metric distance change over time (from
      baseline to follow-up), on the raw volumes and metric distances, and on principal
      components from various types of PCA analysis. We provide a detailed comparison
      of the performance of these classifiers and guidelines for their practical use.
      Moreover, combining the information conveyed by volume and metric distance
      measures by PCA can provide a better biomarker for detection of dementia compared
      to volume, metric distance, or both.

PMID- 21875413
TI  - Targeting protein-protein and protein-nucleic acid interactions for anti-HIV
      therapy.
AB  - Protein-protein and protein-nucleic acid interactions are involved in many
      regulatory cellular pathways, playing a key role in cell growth and
      proliferation, as well as in the progression and development of various diseases
      such as infectious diseases. Especially in the anti-AIDS research, protein
      protein and protein-nucleic acid complexes are being considered as promising
      targets for pharmaceutical interventions aimed at overcoming the drug resistance
      observed for most of the classic enzyme inhibitors. Consequently, more and more
      protein-protein and protein-nucleic acid interaction inhibitors have being
      identified and developed as candidate agents for antiretroviral therapy. Here, we
      review the state of the art in the discovery and development of protein-protein
      and protein-nucleic acid interaction inhibitors that block the main steps of the
      HIV-1 replication cycle, giving a medicinal chemistry-oriented view of strategies
      for inhibiting these regulatory interactions that are involved in the entry
      process, in the dimerization of reverse transcriptase and protease enzymes, and
      in the activity of the nucleocapsid protein by means of small molecular potential
      therapeutic agents.

PMID- 21875415
TI  - Sonoporation using microbubbles promotes lipofectamine-mediated siRNA
      transduction to rat retina.
AB  - Ultrasound-targeted microbubble destruction(UTMD) has been utilized to deliver
      naked siRNA into cells in in vitro settings. But whether UTMD can safely deliver
      naked siRNA into in vivo cells have remained unknown. This work was performed to
      investigate the feasibility of UTMD-enhanced naked siRNA transduction (or
      combined with Lipofectamine 2000) in vivo retinal cells and compare the
      performance between UTMD and ultrasonic irradiation alone in this enhancing
      effect. A dose of Cy3-labeled siRNA was injected into the vitreous cavity of rat
      eyes under the different conditions of Lipofectamine 2000 or/and UTMD.
      Transduction efficiency was assessed by fluorescence microscopy and flow
      cytometry. Cell and tissue damage was assessed by trypan blue exclusion test and
      hematoxylineosin staining, respectively. The quantity and the density of
      transducted cells in the group received Lipofectamine 2000 and UTMD was far more
      than that in other groups. The number of transducted cells in the group received
      Lipofectamine 2000 and ultrasonic irradiation alone was slightly more than that
      in the group received Lipofectamine 2000. Cy3-siRNA-positive cells can also seen
      in the group received UTMD alone, although the transduction efficiency is
      extremely low. Cell viability in each group was more than 90%, and retinal
      architecture in each group was well preserved. These results indicated that UTMD,
      with a significantly higher performance than ultrasonic irradiation alone, can
      effectively enhance the Lipofectamine 2000-mediated naked siRNA transduction in
      vivo reinal cells without any cell or tissue damage. This method can serve as a
      novel approach to treat the diseases of eye ground.

PMID- 21875416
TI  - Endothelial dysfunction in uremic patients on continuous ambulatory peritoneal
      dialysis (CAPD).
AB  - Endothelial dysfunction is associated with diabetic micro- and macroangiopathy as
      well as with the decline in creatinine clearance. It has been suggested that
      endothelial dysfunction presents in patients (pts) on continuous ambulatory
      peritoneal dialysis (CAPD). The objective of this study was to examine the plasma
      biomarkers of endothelial dysfunction and their association with IMT of carotid
      arteries in diabetic and non-diabetic patients on CAPD. This study included 37
      CAPD pts (25 with type II diabetes and 12 non-diabetic pts) mean age 59.2 years
      +/- 2.48. Plasma von Willebrand factor (vWF) activity, serum albumin, glucose,
      total cholesterol, triglycerides and lipoprotein (a) levels, as well as serum
      level of homocysteine, parathyroid hormone (PTH) in plasma and microalbuminuria
      was determined. Ultrasound examination of carotid arteries was performed in all
      patients by measured bilateral intima-media thickness of carotid artery (CIMT).
      Mean IMT value was significantly higher in type 2 DM patients (0.86 +/- 0.04 mm)
      compared to non-diabetic patients (0.52 +/- 0.06 mm) on peritoneal dialysis
      (p<0.0001). There was also a significant difference in lipids /triglycerides and
      Lp (a)/, procoagulation (fibrinogen, von Wilebrand factor, factor VIII) and
      inflammatory markers (CRP) level between type 2 DM and non-diabetic CAPD
      patients. A stepwise multiple regression analysis revealed that log triglycerides
      and factor VIII were independent factors for the IMT. The results of this
      research impose that diabetic type 2 CAPD patients have developed systemic
      alteration of endothelial function and higher risk of cardiovascular
      complications compared to non-diabetic CAPD patients.

PMID- 21875414
TI  - Insulin-like growth factor: current concepts and new developments in cancer
      therapy.
AB  - The insulin-like growth factor (IGF) family and the IGF-1 receptor (IGF-1R) play
      an important role in cancer. This intricate and complex signaling pathway
      provides many opportunities for therapeutic intervention, and several novel
      therapeutics aimed at the IGF-1R, particularly monoclonal antibodies and small
      molecule tyrosine kinase inhibitors, are under clinical investigation. This
      article provides a patent overview of the IGF signaling pathway and its
      complexity, addresses the justification for the use of IGF-1R-targeted therapy,
      and reviews the results of in vivo and in vitro novel therapeutics. Over the past
      year, the completion of several phase I, II, and III trials have provided
      interesting new information about the clinical activity of these novel compounds,
      particularly CP-751,871, IMC-A12, R1507, AMG-479, AVE-1642, MK-0646, XL-228, OSI
      906, and BMS-754807. We review the important preliminary results from clinical
      trials with these compounds and conclude with a discussion about future
      therapeutic efforts.

PMID- 21875417
TI  - The effects of tadalafil on renal ischemia reperfusion injury: an experimental
      study.
AB  - Many pharmacological agents were investigated for the prevention of renal
      ischemic reperfusion (I/R) injury as well as the phosphodiesterase (PDE)
      inhibitors. The aim of the study was to examine the possible renoprotective
      effect of a member in this family, tadalafil (Td) on I/R injury. Thirty-six
      Spraque Dawley rats were allocated to six groups as; control, sham, ischemia (I),
      ischemia/reperfusion (I/R), Td pretreatment ischemia (Td/I) and Td pretreatment
      ischemia/reperfusion (Td/IR) groups. Right nephrectomy was performed in all
      groups. Td was dissolved in saline solution and given as a single dose (1mg/kg)
      through an orogastrictube 60 min before the operation in the Td pretreatment
      groups. In ischemia group the left renal pedicle was occluded for 45 minutes and
      after than underwent left nephrectomy. In I/R group left renal pedicle was
      occluded for 45 minutes, reperfused for 1hour and after then underwent
      nephrectomy. The left kidneys were evaluated after standard laboratory procedures
      with regard to tubular morphology, and leukocyte infiltration. The data were
      analyzed by using Kruskal-Wallis test to determine differences among the groups.
      A p value of < 0.05 was considered significant. Renal tubular damage was
      significant increased in the ischemia and I/R group (Groups III and IV) when
      compared to those in the sham group (Group II), (p = 0.004, 0.004, respectively).
      Tubular damage, in the Td pretreatment ischemia (Td/I) (Group V) and Td
      pretreatment ischemia/reperfusion (Td/IR) (Group VI) were less than that in the
      ischemia group (Group III) (p= 0.010, p= 0.025, respectively). Td administration
      prior to the renal I/R injury attenuated these morphological disarrangements,
      which were observed in renal I/R. Tubular necrosis, which may be considered as an
      important issue of the developing renal injury, was also completely prevented
      with Td administration.

PMID- 21875418
TI  - An experimental study on the application of radionuclide imaging in repair of the
      bone defect.
AB  - The aim of our study was to validate the effect of radionuclide imaging in early
      monitoring of the bone's reconstruction, the animal model of bone defect was made
      on the rabbits repaired with HA artificial bone. The ability of bone defect
      repair was evaluated by using radionuclide bone imaging at 2, 4, 8 and 12 weeks
      postoperatively. The results indicate that the experimental group stimulated more
      bone formation than that of the control group. The differences of the bone
      reconstruction ability were statistically significant (p<0.05). The nano-HA
      artificial has good bone conduction, and it can be used for the treatment of bone
      defects. Radionuclide imaging may be an effective and first choice method for the
      early monitoring of the bone's reconstruction.

PMID- 21875419
TI  - Cholesteryl ester transfer protein, low density lipoprotein particle size and
      intima media thickness in patients with coronary heart disease.
AB  - Cholesteryl ester transfer protein (CETP) plays a key role in reverse cholesterol
      transport and high density lipoprotein (HDL) metabolism. Predominance of small,
      dense LDL particles is associated with an increased risk of atherosclerosis and
      coronary heart disease (CHD).The aim of the study was to determine the potential
      relationship between the CETP concentration and low density lipoprotein (LDL)
      particle size and their association with intima media thickness (IMT) in patients
      with CHD. Lipid parameters, CETP concentration and LDL particle size were
      determined in 100 healthy subjects (control group) and in 100 patients with CHD,
      aged 43 to 77 years. Plasma CETP concentrations were measured by an enzyme-linked
      immuno-sorbent assay with two different monoclonal antibodies. LDL subclasses
      were separated by nondenaturing polyacrilamide 3-31% gradient gel
      electrophoresis. CETP concentration was higher in patients compared to controls
      (2.02 +/- 0.75 mg/ml vs. 1.74 +/- 0.63 mg/ml, p<0.01). Mean LDL particle size
      (nm) was significantly smaller in patients than in controls (24.5 +/- 1.1 vs.
      26.1 +/- 0.9; p<0.001). There was no relation between LDL particle size and CETP
      concentration (r=-0.1807, p=0.072). Age, diastolic blood pressure, CETP
      concentration and LDL particle size were independent factors for determing IMT by
      multiple linear regression analysis. They accounted for 35.2 % of the observed
      variability in IMT. CETP is not an independent contributor of LDL particle size.
      CETP might play a role in determining lipoprotein distributions, but did not seem
      to be the sole factor in the formation of small LDL particles.

PMID- 21875420
TI  - Lung 99mTc-MIBI scintigraphy: impact on diagnosis of solitary pulmonary nodule.
AB  - Most of today available non-invasive procedures cannot clearly determinate
      between benign and malignant solitary pulmonary nodules (SPN). The purpose of the
      study was to assess the possibility of using 99mTc labeled hexakis-2
      methoxyisobutylisonitrile (99mTc-MIBI) to differentiate benign from malignant
      SPN. Sixty patients were included in the study if the CT scan showed
      indeterminate SPN. Prior to definitive diagnosis 99mTc-MIBI single photon
      emission computerized tomography (SPECT) was performed: early scan 10 minutes and
      delayed 60-120 minutes after the intravenous injection of 740 MBq 99mTc-MIBI
      using dual-headed Gamma camera. The results were considered positive if there was
      an increased accumulation of the radiopharmaceutical in the area of the lung
      corresponding to the location of the lesion. The mean nodule size +/- SD measured
      on CT scan was 2.96 cm. Lung cancer was diagnosed in 30/60 patients (14
      squamocellular, 10 adenocarcinoma, 3 large-cell and 3 microcellular lung
      carcinomas). Of the 30 patients with malignant lesions, 27 patients (90%) had
      positive 99mTc-MIBI scan results by qualitative assessment. Among benign lesions,
      23/30 (76.7%) were negative on 99mTc-MIBI scan. The size and PH report of SPN is
      statistically significantly influencing on 99mTc-MIBI accumulation in the SPN
      (p<0.01). The sensitivity, specificity, accuracy, positive and negative
      predictive value were 90%, 76.6%, 79.4%, 88.5% and 83.3% respectively. 99mTc-MIBI
      SPECT is an inexpensive non-invasive diagnostic procedure which might be useful
      diagnostic modality in the evaluation of SPN. Easy availability and low cost
      makes 99mTc-MIBI SPECT an attractive method in evaluating SPN.

PMID- 21875421
TI  - Radiographic estimation in seropositive and seronegative rheumatoid arthritis.
AB  - Long since it have been suggested that a subpopulation of patients with
      rheumatoid arthritis, diagnosed with negative rheumatoid factor tests, represents
      a clinical entity quite distinct from that of seropositive rheumatoid arthritis
      (RA). Our aim was to establish a scientific comparative analysis between
      seronegative and seropositive rheumatoid arthritis, regarding some radiological
      and clinical parameters, applied for the first time on patients from Kosovo. Two
      hundred fifty patients with rheumatoid arthritis according to the American
      College of Rheumatology criteria were retrospectively studied by analysis the
      radiographic damage and clinical parameters of the disease, using a data base.
      All examinees were between 25-60 years of age (Xb=49.96, SD=10.37) with disease
      duration between 1-27 years (Xb = 6.41, SD=6.47). All patients underwent a
      standardised evaluation radiographs. Baseline standardised poster anterior
      radiographs of hands and feet and radiographs of other joints, depending on
      indications, were assessed. Erythrocyte sedimentation rate values correlated with
      the radiological damages and statistical difference was found for seronegative
      subset (r=0.24, p<0.01). Longer duration of the disease resulted in the increase
      of radiological changes in both subsets (r=0.66, p<0.01) seronegative, (r=0.49,
      p<0.01) seropositive. Anatomic changes of IInd and IIIrd level were nearly
      equally distributed in both subsets, 76 (60.8%) seronegative, 75 (60%)
      seropositive. Radiological damages are nearly equal in both subsets, elevate in
      relation to the duration of the disease and correlate with ESR values. Regarding
      the sero-status, differences within sex, with some exceptions, are not relevant.
      Although there are some definite quantitative and qualitative differences
      regarding sero-status, obviously there is a great deal of overlap between the two
      groups.

PMID- 21875422
TI  - Using the BITOLA system to identify candidate genes for Parkinson's disease.
AB  - Complexity of multifactorial diseases as Parkinson's disease (PD) often
      complicate identifying causal genetic factors by traditional approaches such as
      positional cloning and candidate gene analyses. PD is etiologically and
      genetically complex disease and second most common neurodegenerative disorder
      after Alzheimer's disease. The most cases of PD are idiopathic and small growing
      subset of individuals have single gene defect as the cause. The main goal of this
      research was to identify the potential candidate genes for idiopathic PD by using
      biomedical discovery support system (BITOLA). For detecting the potential
      candidate genes for PD was used opened system of bioinformatics tool BITOLA. Data
      of chromosome location, tissue specific expression of potential candidate genes
      and their potential association with PD were obtained from Medline, Locus Link,
      Gene Cards and OMIM. By using BITOLA system is identified 17 genes as potential
      candidate genes for PD. The role of three genes (MAPT, PARK2, UCHL1) in PD were
      confirmed earlier. Discovering the novel candidate genes for multifactiorial
      diseases by using specially mentioned bioinformatics tool BITOLA could offer the
      new opportunity for researching genetics base of PD without using tissue samples
      of patients.

PMID- 21875423
TI  - Celiac disease and fulminant T lymphoma detected too late in a 35-year-old female
      patient: case report.
AB  - Celiac disease is the most common chronic gastroenterological autoimmune disease
      characterized by gluten intolerance. The diagnosis of celiac disease and
      enteropathy-associated T cell lymphoma is often made when it is too late.Case
      report describes a 35-year-old female patient managed for one year under the
      diagnosis of inflammatory bowel disease and admitted to our hospital for
      exacerbation of the underlying disease. However, inflammatory bowel disease was
      ruled out by diagnostic work-up, while the clinical picture and the findings
      obtained raised suspicion of lymphoma. The patient's condition was additionally
      complicated by fulminant course of the disease and ileus. CONCLUSION: Early
      diagnosis and appropriate treatment of the disease, and follow up of family
      members are crucial to prevent intestinal lymphoma development.

PMID- 21875424
TI  - Choledochal cyst: presentation of the disease with a case report.
AB  - Choledochal cyst is a rare disease of the biliary tract. There are five main
      types of choledochal cysts with a few recognized sub-types. The etiology of
      choledochal cysts still is unclear. The incidence of biliary tract cancer in
      patients with choledochal cysts increases with age. In the past, choledochal
      cysts were often treated using drainage procedures; however, the optimal
      treatment used today is likely to involve the complete excision of the
      extrahepatic duct, cholecystectomy, and Roux-en-Y hepaticojejunostomy. Endoscopic
      treatment of type III choledochocele should be limited to the management of
      smaller lesions. We report a case of 75 years old patient with distal choledochal
      diverticuly, Todani's type III- choledochocele. Delay in the diagnosis increases
      the frequency of associated biliary pathology, malignant alternation and
      suboptimal surgical therapy. Often, intraoperative finding of choledochal cyst is
      the first contact with this rear entity, so awareness of possible presence of
      this uncommon disease is very important for surgeon.

PMID- 21875425
TI  - Are pregnant women in New Zealand iodine deficient? A cross-sectional survey.
AB  - Severe iodine deficiency in pregnancy can result in cretinism. There is growing
      concern that less severe iodine deficiency may also affect fetal growth and
      development. A handful of prior small New Zealand studies focussed on pregnant
      women living in Dunedin. This study utilised biochemical, clinical and dietary
      indices to assess iodine status of 170 women living throughout New Zealand. The
      median urinary iodine concentration (UIC) of the women was 38 MUg/L, well below
      the 150 MUg/L cut-off value that indicates adequate iodine status; 7% of women
      had goitre. Not surprisingly, iodine intake was also low at 48 MUg/day. The
      majority of women had TSH and FT4 concentrations within pregnant reference
      ranges, suggesting that despite the low UIC observed in these women, thyroid
      hormone production appeared unaffected.

PMID- 21875426
TI  - Adherence to evidence-based guidelines for the management of pyelonephritis in
      pregnancy.
AB  - BACKGROUND:   Pyelonephritis occurs in approximately two per cent of pregnancies
      and can cause significant maternal and fetal morbidity and mortality. Evidence
      based guidelines recommend appropriate antibiotic therapy, urine culture for test
      of cure after treatment and monthly follow-up cultures until delivery. AIMS:   To
      evaluate adherence to guidelines for the management of antepartum pyelonephritis
      within an Australian obstetric population and to assess associations with
      noncompliance. METHODS:   A retrospective study was performed for the 103
      pregnant women admitted with pyelonephritis between January 2001 and December
      2009 at the Royal Brisbane and Women's Hospital, a tertiary referral obstetric
      hospital. We assessed baseline characteristics, the frequency of appropriate
      treatment and follow-up, and any associations among these. RESULTS:   The
      guideline recommended antibiotic treatment was prescribed in 90.3% of women. Of
      the women with antibiotic-resistant organisms, 31.6% had their antibiotics
      changed appropriately. The test of cure urine culture was performed in only 35.0%
      of women after treatment completion. Inadequate long-term follow-up occurred in
      60.2% of the cohort studied. Inappropriate follow-up was associated with low
      socioeconomic status (P=0.04), unemployment (P=0.04) and the absence of a test of
      cure urine culture (P=0.001). CONCLUSION:   The empiric treatment of antepartum
      pyelonephritis is generally appropriate; however, antibiotic changes for
      bacterial resistance are inadequate. Test of cure and monthly follow-up urine
      cultures are infrequently performed despite their recommendation in published
      treatment guidelines.

PMID- 21875427
TI  - CFTR mutation screening in an assisted reproductive clinic.
AB  - INTRODUCTION:   Cystic fibrosis (CF) is the most common deleterious single-gene
      recessive disorder in non-Hispanic Caucasians. Mutations within the CF
      transmembrane receptor (CFTR) gene produce a variable phenotype, including
      pulmonary disease, pancreatic insufficiency, meconium ileus and infertility.
      Screening of antenatal/preconception patients to identify CFTR mutation carriers
      has been shown to reduce the incidence of CF-affected babies at birth. The
      application of preconception screening to assisted reproductive technology (ART)
      patients enables carrier couples a choice between prenatal screening and
      preimplantation genetic diagnosis (PGD). AIM:   To screen patients entering an
      infertility clinic, for 30 common CFTR mutations, and to detect carrier patients
      prior to initiating assisted reproductive treatment. METHOD:   DNA from 5600
      infertility patients was screened using a PCR/OLA kit for 30 CFTR mutations. All
      identified carriers and carrier couples were offered genetic counselling.
      Prenatal testing and PGD for CFTR mutations were offered to carrier couples where
      appropriate. RESULTS:   A total of 5600 patients were screened for 30 CFTR
      mutations with 261 carriers being identified and at a significantly increased
      carrier rate of one in 21.5 (4.66% +/- 0.55%). R117H/c.350G>A was significantly
      increased in this infertile population and accounted for 13.8% of all mutations
      identified. Twelve carrier couples were identified, and nine carrier couples had
      at least one cycle of PGD for CFTR mutations. CONCLUSION:   The carrier rate of
      CFTR mutations is elevated in patients presenting for infertility treatment, and
      preconception screening should be encouraged in all patients entering ART
      clinics.

PMID- 21875428
TI  - Comparative proteome and lipid profiles of bovine epididymosomes collected in the
      intraluminal compartment of the caput and cauda epididymidis.
AB  - During the epididymal maturation, spermatozoa interact with different populations
      of epididymosomes and sequentially acquire some epididymosome-associated proteins
      critical to sperm functions. Although very few proteins associated with
      epididymosomes have been identified, the physiological importance of these
      vesicles in the sperm maturation remains unclear. To document these relevant
      issues, lipid and protein analysis of epididymosomes from caput and cauda
      epididymal fluids was determined. Lipid analysis revealed a particular
      composition of specific phospholipids in these vesicles; the levels of
      phosphatidyl-ethanolamine, phosphatidyl-inositol and phosphatidyl-choline being
      higher in caput epididymosomes. From the 555 and 438 proteins identified in caput
      and cauda-derived epididymosomes, respectively, 231 proteins were identified in
      both types of epididymosome. Proteins exclusively identified in caput and cauda
      epididymosomes are mainly enzymes and transporter molecules. The presence of
      several glycan-modifying enzymes is the hallmark of the caput epididymosomes
      proteome. Among the common proteins in both types of epididymosome, a subset of
      Rab and SNARE proteins implicated in vesicle trafficking and membrane fusion were
      identified. Together, these data suggest that epididymosome-associated proteins
      are involved in various molecular functions suggesting that during the epididymal
      transit, spermatozoa interact with different populations of epididymosomes, which
      could modify the male gamete in a sequential manner.

PMID- 21875429
TI  - Trends in sperm count in Finnish men.

PMID- 21875430
TI  - Critical appraisal of clinical practice guidelines for diagnosis and treatment of
      hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is the third most common
      reason for cancer-related death worldwide. Many countries either lack appropriate
      clinical practice guidelines for the diagnosis and treatment of HCC or the
      quality of their guidelines has never been evaluated. The main objective of our
      work was to identify published HCC guidelines and assess their quality with the
      Appraisal of Guidelines for Research and Evaluation instrument (AGREE) and their
      suitability regarding adaptation for future guidelines. METHODS: We performed a
      systematic literature search on HCC clinical practice guidelines of MEDLINE,
      National Guidelines Clearinghouse and the Guidelines International Network.
      Methodological quality of selected guidelines was assessed by the AGREE
      instrument, Version 2001. RESULTS: A total of 286 citations were screened and 32
      relevant guidelines were identified. Overall, the guidelines performed well in
      the clarity and presentation domain with a mean score of 67%, followed by scope
      and purpose (55%) and rigor of development (50%). In contrast, poor scores were
      given for the remaining domains: stakeholder involvement (23%), applicability
      (28%) and editorial independence (31%). According to the AGREE instrument, four
      guidelines can be strongly recommended, 18 with provisos and alterations while
      the remaining cannot be recommended for adaptation due to poor methodological
      quality. CONCLUSION: Although existing HCC guidelines may accurately reflect
      agreed clinical practice, many guidelines lack proper methodological quality.
      Future guidelines should place more emphasis on these methodological
      shortcomings.

PMID- 21875431
TI  - Clock-hour laminar displacement and age in primary open-angle glaucoma and normal
      tension glaucoma.
AB  - BACKGROUND: To find out the relationship between laminar displacement and age
      between patients with primary open-angle glaucoma and normal tension glaucoma.
      DESIGN: Retrospective study conducted at a tertiary university hospital.
      PARTICIPANTS OR SAMPLES: Twenty-six eyes of 26 primary open-angle glaucoma
      patients and 52 eyes of 52 normal tension glaucoma patients. METHODS: Patients
      were scanned with a Stratus optical coherence tomography apparatus to measure the
      retinal nerve fibre layer thickness and to visualize the cross-sectional laminar
      displacement of 12 clock-hour segments, 30 degrees each. Depth1 was defined as
      the longest distance between the retinal pigment epithelium and the anterior
      laminar cribrosa surface, which represents the amount of laminar displacement.
      MAIN OUTCOME MEASURE: Partial correlation coefficients adjusted by mean deviation
      and intraocular pressure between (i) retinal nerve fibre layer thickness and age,
      and (ii) Depth1 and age. RESULTS: In the primary open-angle glaucoma group,
      strong negative correlations (approximately -0.343 ~ -0.738) were found between
      Depth1 and age. Eight of 12 clock-hour segments' correlations were significant
      after Bonferroni correction (alpha = 0.0021; 24 comparisons). However, no
      significant correlations were found between Depth1 and age in the normal tension
      glaucoma group. When the correlation coefficients were compared between the two
      groups, eight clock-hour segments showed significant differences after Bonferroni
      correction. CONCLUSIONS: The significantly different correlation between laminar
      displacement and age between primary open-angle glaucoma and normal tension
      glaucoma patients may suggest a different role of the lamina cribrosa to the
      disease.

PMID- 21875432
TI  - Supplementation with a new therapeutic oxygen carrier reduces chronic fibrosis
      and organ dysfunction in kidney static preservation.
AB  - Static preservation is currently the most widely used organ preservation
      strategy; however, decreased donor organ quality is impacting outcome negatively.
      M101 is an O2 carrier with high-oxygen affinity and the capacity to function at
      low temperatures. We tested the benefits of M101 both in vitro, on cold preserved
      LLC-PK1, as well as in vivo, in a large white pig kidney autotransplantation
      model. In vitro, M101 supplementation reduced cold storage-induced cell death. In
      vivo, early follow-up demonstrated superiority of M101-supplemented solutions,
      lowering the peak of serum creatinine and increasing the speed of function
      recovery. On the longer term, supplementation with M101 reduced kidney
      inflammation levels and maintained structural integrity, particularly with
      University of Wisconsin (UW). At the end of the 3-month follow-up, M101
      supplementation proved beneficial in terms of survival and function, as well as
      slowing the advance of interstitial fibrosis. We show that addition of M101 to
      classic organ preservation protocols with UW and Histidine-Tryptophane
      Ketoglutarate, the two most widely used solutions worldwide in kidney
      preservation, provides significant benefits to grafts, both on early function
      recovery and outcome. Simple supplementation of the solution with M101 is easily
      translatable to the clinic and shows promises in terms of outcome.

PMID- 21875433
TI  - Increased fracture rate in women with breast cancer: a review of the hidden risk.
AB  - BACKGROUND: Women with breast cancer, particularly individuals diagnosed at a
      relatively early age, have an increased incidence of fractures. Fractures can
      have serious clinical consequences including the need for major surgery,
      increased morbidity and mortality, increased cost of disease management, and
      reduced quality of life for patients. The primary cause of the increased fracture
      risk appears to be an accelerated decrease in bone mineral density (BMD)
      resulting from the loss of estrogenic signaling that occurs with most treatments
      for breast cancer, including aromatase inhibitors. However, factors other than
      BMD levels alone may influence treatment decisions to reduce fracture risk in
      this setting. Our purpose is to review current evidence for BMD loss and fracture
      risk during treatment for breast cancer and discuss pharmacologic means to reduce
      this risk. RESULTS: Fracture risk during treatment for breast cancer may be
      influenced by the rate of BMD loss and the consequent rapid alterations in bone
      microarchitecture, in addition to the established fracture risk factors in
      postmenopausal osteoporosis. The rapid decrease in BMD during adjuvant
      chemoendocrine therapy for breast cancer may necessitate more aggressive
      pharmacotherapy than is indicated for healthy postmenopausal women who develop
      osteoporosis. Over the last few years, clinical trials have established the
      effectiveness of bisphosphonates and other antiresorptive agents to preserve BMD
      during adjuvant therapy for early breast cancer. In addition, some
      bisphosphonates (eg, zoledronic acid) may also delay disease recurrence in women
      with hormone-responsive tumors, thereby providing an adjuvant benefit in addition
      to preserving BMD and potentially preventing fractures. CONCLUSIONS: It is likely
      that a combined fracture risk assessment (eg, as in the WHO FRAX algorithm) will
      more accurately identify both women with postmenopausal osteoporosis and women
      with breast cancer who require bone-protective therapy.

PMID- 21875434
TI  - Joint analysis of quantitative trait loci and major-effect causative mutations
      affecting meat quality and carcass composition traits in pigs.
AB  - BACKGROUND: Detection of quantitative trait loci (QTLs) affecting meat quality
      traits in pigs is crucial for the design of efficient marker-assisted selection
      programs and to initiate efforts toward the identification of underlying
      polymorphisms. The RYR1 and PRKAG3 causative mutations, originally identified
      from major effects on meat characteristics, can be used both as controls for an
      overall QTL detection strategy for diversely affected traits and as a scale for
      detected QTL effects. We report on a microsatellite-based QTL detection scan
      including all autosomes for pig meat quality and carcass composition traits in an
      F2 population of 1,000 females and barrows resulting from an intercross between a
      Pietrain and a Large White-Hampshire-Duroc synthetic sire line. Our QTL detection
      design allowed side-by-side comparison of the RYR1 and PRKAG3 mutation effects
      seen as QTLs when segregating at low frequencies (0.03-0.08), with independent
      QTL effects detected from most of the same population, excluding any carrier of
      these mutations. RESULTS: Large QTL effects were detected in the absence of the
      RYR1 and PRKGA3 mutations, accounting for 12.7% of phenotypic variation in loin
      colour redness CIE-a* on SSC6 and 15% of phenotypic variation in glycolytic
      potential on SSC1. We detected 8 significant QTLs with effects on meat quality
      traits and 20 significant QTLs for carcass composition and growth traits under
      these conditions. In control analyses including mutation carriers, RYR1 and
      PRKAG3 mutations were detected as QTLs, from highly significant to suggestive,
      and explained 53% to 5% of the phenotypic variance according to the trait.
      CONCLUSIONS: Our results suggest that part of muscle development and backfat
      thickness effects commonly attributed to the RYR1 mutation may be a consequence
      of linkage with independent QTLs affecting those traits. The proportion of
      variation explained by the most significant QTLs detected in this work is close
      to the influence of major-effect mutations on the least affected traits, but is
      one order of magnitude lower than effect on variance of traits primarily affected
      by these causative mutations. This suggests that uncovering physiological traits
      directly affected by genetic polymorphisms would be an appropriate approach for
      further characterization of QTLs.

PMID- 21875435
TI  - Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower
      airway inflammation model.
AB  - BACKGROUND: Inhalation of N-chlorotaurine (NCT), an endogenous new broad spectrum
      non-antibiotic anti-infective, has been shown to be very well tolerated in the
      pig model recently. In the present study, inhaled NCT was tested for tolerability
      and efficacy in the infected bronchopulmonary system using the same model.
      METHODS: Anesthetized pigs were inoculated with 20 ml of a solution containing
      approximately 108 CFU/ml Streptococcus pyogenes strain d68 via a duodenal tube
      placed through the tracheal tube down to the carina. Two hours later, 5 ml of 1%
      NCT aqueous solution (test group, n = 15) or 5 ml of 0.9% NaCl (control group, n
      = 16) was inhaled via the tracheal tube connected to a nebulizer. Inhalation was
      repeated every hour, four times in total. Lung function and haemodynamics were
      monitored. Bronchoalveolar lavage samples were removed for determination of
      colony forming units (CFU), and lung samples for histology. RESULTS: Arterial
      pressure of oxygen (PaO2) decreased rapidly after instillation of the bacteria in
      all animals and showed only a slight further decrease at the end of the
      experiment without a difference between both groups. Pulmonary artery pressure
      increased to a peak 1-1.5 h after application of the bacteria, decreased in the
      following hour and remained constant during treatment, again similarly in both
      groups. Histology demonstrated granulocytic infiltration in the central parts of
      the lung, while this was absent in the periphery. Expression of TNF-alpha, IL-8,
      and haemoxygenase-1 in lung biopsies was similar in both groups. CFU counts in
      bronchoalveolar lavage came to 170 (10; 1388) CFU/ml (median and 25 and 75
      percentiles) for the NCT treated pigs, and to 250 (10; 5.5 * 105) CFU/ml for NaCl
      treated pigs (p = 0.4159). CONCLUSIONS: Inhaled NCT at a concentration of 1%
      proved to be very well tolerated also in the infected bronchopulmonary system.
      This study confirms the tolerability in this delicate body region, which has been
      proven in healthy pigs previously. Regarding efficacy, no conclusions can be
      drawn, mainly because of the limited test period of the model.

PMID- 21875436
TI  - Activation of monocytes and cytokine production in patients with peripheral
      atherosclerosis obliterans.
AB  - BACKGROUND: Arterial peripheral disease is a condition caused by the blocked
      blood flow resulting from arterial cholesterol deposits within the arms, legs and
      aorta. Studies have shown that macrophages in atherosclerotic plaque are highly
      activated, which makes these cells important antigen-presenting cells that
      develop a specific immune response, in which LDLox is the inducing antigen. As
      functional changes of cells which participate in the atherogenesis process may
      occur in the peripheral blood, the objectives of the present study were to
      evaluate plasma levels of anti-inflammatory and inflammatory cytokines including
      TNF-alpha, IFN-gamma, interleukin-6 (IL-6), IL-10 and TGF-beta in patients with
      peripheral arteriosclerosis obliterans, to assess the monocyte activation level
      in peripheral blood through the ability of these cells to release hydrogen
      peroxide (H2O2) and to develop fungicidal activity against Candida albicans (C.
      albicans) in vitro. METHODS: TNF-alpha, IFN-gamma, IL-6, IL-10 and TGF-beta from
      plasma of patients were detected by ELISA. Monocyte cultures activated in vitro
      with TNF-alpha and IFN-gamma were evaluated by fungicidal activity against C.
      albicans by culture plating and Colony Forming Unit (CFU) recovery, and by H2O2
      production. RESULTS: Plasma levels of all cytokines were significantly higher in
      patients compared to those detected in control subjects. Control group monocytes
      did not release substantial levels of H2O2 in vitro, but these levels were
      significantly increased after activation with IFN-gamma and TNF-alpha. Monocytes
      of patients, before and after activation, responded less than those of control
      subjects. Similar results were found when fungicidal activity was evaluated. The
      results seen in patients were always significantly smaller than among control
      subjects. CONCLUSIONS: The results revealed an unresponsiveness of patient
      monocytes in vitro probably due to the high activation process occurring in vivo
      as corroborated by high plasma cytokine levels.

PMID- 21875437
TI  - Enchanced levels of apolipoprotein M during HBV infection feedback suppresses HBV
      replication.
AB  - BACKGROUND: Chronic liver diseases can interfere with hepatic metabolism of
      lipoproteins, apolipoproteins. Hepatitis B virus (HBV) is a major etiological
      agent causing acute and chronic liver diseases. Apolipoprotein M (ApoM) is a high
      density lipoprotein (HDL) apolipoprotein and exclusively expressed in the liver
      parenchyma cells and in the tubular cells of the kidney. This study was to
      determine the correlation between HBV infection and ApoM expression. MATERIALS
      AND METHODS: Serum ApoM levels in patients with HBV infection and in healthy
      individuals were measured by ELISA, ApoM mRNA expression were determined by RT
      PCR, and the expression of S and E proteins of HBV, as well as the synthesis of
      viral DNA were measured by ELISA and real-time PCR. RESULTS: The levels of serum
      ApoM was significantly elevated in patients as compared to healthy individuals (P
      < 0.001), ApoM promoter activity, mRNA and protein expression were all stimulated
      in cells transfected with infectious HBV clone. In addition, ApoM decreases the
      expression of S and E proteins of HBV and the synthesis of viral DNA. CONCLUSION:
      Raised ApoM levels in HBV infection may in turn suppress HBV replication, one of
      the protective mechanisms of nature.

PMID- 21875438
TI  - Classification of dendritic cell phenotypes from gene expression data.
AB  - BACKGROUND: The selection of relevant genes for sample classification is a common
      task in many gene expression studies. Although a number of tools have been
      developed to identify optimal gene expression signatures, they often generate
      gene lists that are too long to be exploited clinically. Consequently,
      researchers in the field try to identify the smallest set of genes that provide
      good sample classification. We investigated the genome-wide expression of the
      inflammatory phenotype in dendritic cells. Dendritic cells are a complex group of
      cells that play a critical role in vertebrate immunity. Therefore, the prediction
      of the inflammatory phenotype in these cells may help with the selection of
      immune-modulating compounds. RESULTS: A data mining protocol was applied to
      microarray data for murine cell lines treated with various inflammatory stimuli.
      The learning and validation data sets consisted of 155 and 49 samples,
      respectively. The data mining protocol reduced the number of probe sets from
      5,802 to 10, then from 10 to 6 and finally from 6 to 3. The performances of a set
      of supervised classification models were compared. The best accuracy, when using
      the six following genes --Il12b, Cd40, Socs3, Irgm1, Plin2 and Lgals3bp-- was
      obtained by Tree Augmented Naive Bayes and Nearest Neighbour (91.8%). Using the
      smallest set of three genes --Il12b, Cd40 and Socs3-- the performance remained
      satisfactory and the best accuracy was with Support Vector Machine (95.9%). These
      data mining models, using data for the genes Il12b, Cd40 and Socs3, were
      validated with a human data set consisting of 27 samples. Support Vector Machines
      (71.4%) and Nearest Neighbour (92.6%) gave the worst performances, but the
      remaining models correctly classified all the 27 samples. CONCLUSIONS: The genes
      selected by the data mining protocol proposed were shown to be informative for
      discriminating between inflammatory and steady-state phenotypes in dendritic
      cells. The robustness of the data mining protocol was confirmed by the accuracy
      for a human data set, when using only the following three genes: Il12b, Cd40 and
      Socs3. In summary, we analysed the longitudinal pattern of expression in
      dendritic cells stimulated with activating agents with the aim of identifying
      signatures that would predict or explain the dentritic cell response to an
      inflammatory agent.

PMID- 21875440
TI  - The IMSI procedure improves poor embryo development in the same infertile couples
      with poor semen quality: a comparative prospective randomized study.
AB  - BACKGROUND: Sperm of poor quality can negatively affect embryo development to the
      blastocyst stage. The aim of this comparative prospective randomized study was to
      evaluate the role of an intracytoplasmic morphologically selected sperm injection
      (IMSI) in the same infertile couples included in the programme of
      intracytoplasmic sperm injection (ICSI) due to their indications of male
      infertility which had resulted in all arrested embryos following a prolonged 5
      day culture in previous ICSI cycles. METHODS: Couples exhibiting poor semen
      quality and with all arrested embryos following a prolonged 5-day culture in
      previous ICSI cycles were divided into two groups: Group 1: IMSI group (n = 20)
      with IMSI performed in a current attempt and Group 2: ICSI group (n = 37) with a
      conventional ICSI procedure performed in a current attempt of in vitro
      fertilization. Fertilization rate, embryo development, implantation, pregnancy
      and abortion rates were compared between current IMSI and conventional ICSI
      procedures, and with previous ICSI attempts. RESULTS: The IMSI group was
      characterized by a higher number of blastocysts per cycle than the ICSI group
      (0.80 vs. 0.65) after a prolonged 5-day embryo culture. There was a significantly
      lower number of cycles with all arrested embryos and cycles with no embryo
      transfer in the IMSI group versus the ICSI group (0% vs. 27.0%, p = 0.048). After
      the transfer of embryos at the blastocyst or morula stage (on luteal day 5) a
      tendency toward higher implantation and pregnancy rates per cycle was achieved in
      the IMSI group compared to the ICSI group (17.1% vs. 6.8%; 25.0% vs. 8.1%,
      respectively), although not statistically significant. After IMSI, all
      pregnancies achieved by the blastocyst transfer were normally on-going, whereas
      after ICSI, two of three pregnancies ended in spontaneous abortion. After IMSI,
      two pregnancies were also achieved by the morula stage embryos, whereas after the
      conventional ICSI procedure, embryos at the morula stage did not implant.
      CONCLUSIONS: The IMSI procedure improved embryo development and the laboratory
      and clinical outcomes of sperm microinjection in the same infertile couples with
      male infertility and poor embryo development over the previous ICSI attempts.

PMID- 21875439
TI  - An immunologic portrait of cancer.
AB  - The advent of high-throughput technology challenges the traditional
      histopathological classification of cancer, and proposes new taxonomies derived
      from global transcriptional patterns. Although most of these molecular re
      classifications did not endure the test of time, they provided bulk of new
      information that can reframe our understanding of human cancer biology. Here, we
      focus on an immunologic interpretation of cancer that segregates oncogenic
      processes independent from their tissue derivation into at least two categories
      of which one bears the footprints of immune activation. Several observations
      describe a cancer phenotype where the expression of interferon stimulated genes
      and immune effector mechanisms reflect patterns commonly observed during the
      inflammatory response against pathogens, which leads to elimination of infected
      cells. As these signatures are observed in growing cancers, they are not
      sufficient to entirely clear the organism of neoplastic cells but they sustain,
      as in chronic infections, a self-perpetuating inflammatory process. Yet, several
      studies determined an association between this inflammatory status and a
      favorable natural history of the disease or a better responsiveness to cancer
      immune therapy. Moreover, these signatures overlap with those observed during
      immune-mediated cancer rejection and, more broadly, immune-mediated tissue
      specific destruction in other immune pathologies. Thus, a discussion concerning
      this cancer phenotype is warranted as it remains unknown why it occurs in immune
      competent hosts. It also remains uncertain whether a genetically determined
      response of the host to its own cancer, the genetic makeup of the neoplastic
      process or a combination of both drives the inflammatory process. Here we reflect
      on commonalities and discrepancies among studies and on the genetic or somatic
      conditions that may cause this schism in cancer behavior.

PMID- 21875441
TI  - Exploring the bases for a mixed reality stroke rehabilitation system, part I: a
      unified approach for representing action, quantitative evaluation, and
      interactive feedback.
AB  - BACKGROUND: Although principles based in motor learning, rehabilitation, and
      human-computer interfaces can guide the design of effective interactive systems
      for rehabilitation, a unified approach that connects these key principles into an
      integrated design, and can form a methodology that can be generalized to
      interactive stroke rehabilitation, is presently unavailable. RESULTS: This paper
      integrates phenomenological approaches to interaction and embodied knowledge with
      rehabilitation practices and theories to achieve the basis for a methodology that
      can support effective adaptive, interactive rehabilitation. Our resulting
      methodology provides guidelines for the development of an action representation,
      quantification of action, and the design of interactive feedback. As Part I of a
      two-part series, this paper presents key principles of the unified approach. Part
      II then describes the application of this approach within the implementation of
      the Adaptive Mixed Reality Rehabilitation (AMRR) system for stroke
      rehabilitation. CONCLUSIONS: The accompanying principles for composing novel
      mixed reality environments for stroke rehabilitation can advance the design and
      implementation of effective mixed reality systems for the clinical setting, and
      ultimately be adapted for home-based application. They furthermore can be applied
      to other rehabilitation needs beyond stroke.

PMID- 21875442
TI  - Enhanced annealing of mismatched oligonucleotides using a novel melting curve
      assay allows efficient in vitro discrimination and restriction of a single
      nucleotide polymorphism.
AB  - BACKGROUND: Many SNP discrimination strategies employ natural restriction
      endonucleases to discriminate between allelic states. However, SNPs are often not
      associated with a restriction site and therefore, a number of attempts have been
      made to generate sequence-adaptable restriction endonucleases. In this study, a
      simple, sequence-adaptable SNP discrimination mechanism between a 'wild-type' and
      'mutant' template is demonstrated. This model differs from other artificial
      restriction endonuclease models as cis- rather than trans-orientated regions of
      single stranded DNA were generated and cleaved, and therefore, overcomes
      potential issues of either inefficient or non-specific binding when only a single
      variant is targeted. RESULTS: A series of mismatch 'bubbles' that spanned 0-5-bp
      surrounding a point mutation was generated and analysed for sensitivity to S1
      nuclease. In this model, generation of oligonucleotide-mediated ssDNA mismatch
      'bubbles' in the presence of S1 nuclease resulted in the selective degradation of
      the mutant template while maintaining wild-type template integrity. Increasing
      the size of the mismatch increased the rate of mutant sequence degradation, until
      a threshold above which discrimination was lost and the wild-type sequence was
      degraded. This level of fine discrimination was possible due to the development
      of a novel high-resolution melting curve assay to empirically determine changes
      in Tm (~5.0 degrees C per base-pair mismatch) and to optimise annealing
      conditions (~18.38 degrees C below Tm) of the mismatched oligonucleotide sets.
      CONCLUSIONS: The in vitro 'cleavage bubble' model presented is sequence-adaptable
      as determined by the binding oligonucleotide, and hence, has the potential to be
      tailored to discriminate between any two or more SNPs. Furthermore, the
      demonstrated fluorometric assay has broad application potential, offering a
      rapid, sensitive and high-throughput means to determine Tm and annealing rates as
      an alternative to conventional hybridisation detection strategies.

PMID- 21875444
TI  - Evaluation of stool microbiota signatures in two cohorts of Asian (Singapore and
      Indonesia) newborns at risk of atopy.
AB  - BACKGROUND: Studies have suggested that demographic and lifestyle factors could
      shape the composition of fecal microbiota in early life. This study evaluated
      infant stool microbiota signatures in two Asian populations, Singapore (n = 42)
      and Indonesia (n = 32) with contrasting socioeconomic development, and examined
      the putative influences of demographic factors on these human fecal associated
      bacterial signatures. RESULTS: Longitudinal analysis showed associations of
      geographical origin with Clostridium leptum, Atopobium and Bifidobacterium
      groups. Mode of delivery had the largest effect on stool microbiota signatures
      influencing the abundance of four bacterial groups. Significantly higher
      abundance of bacterial members belonging to the Bacteroides-Prevotella,
      Bifidobacterium and Atopobium groups, but lower abundance of Lactobacilli
      Enterococci group members, were observed in vaginal delivered compared to
      caesarean delivered infants. Demographic factors influencing the structure of
      infants stool microbiota during the first year of life included breastfeeding,
      age of weaning, sibship size and exposure to antibiotics. CONCLUSIONS:
      Differences in stool microbiota signatures were observed in relation to various
      demographic factors. These features may confound studies relating to the
      association of the structure of fecal microbiota and the predisposition to human
      modern disease.

PMID- 21875443
TI  - Gene expression and hypoxia in breast cancer.
AB  - Hypoxia is a feature of most solid tumors and is associated with poor prognosis
      in several cancer types, including breast cancer. The master regulator of the
      hypoxic response is the Hypoxia-inducible factor 1alpha (HIF-1alpha). It is
      becoming clear that HIF-1alpha expression alone is not a reliable marker of tumor
      response to hypoxia, and recent studies have focused on determining gene and
      microRNA (miRNA) signatures for this complex process. The results of these
      studies are likely to pave the way towards the development of a robust hypoxia
      signature for breast and other cancers that will be useful for diagnosis and
      therapy. In this review, we outline the existing markers of hypoxia and recently
      identified gene and miRNA expression signatures, and discuss their potential as
      prognostic and predictive biomarkers. We also highlight how the hypoxia response
      is being targeted in the development of cancer therapies.

PMID- 21875446
TI  - Characteristics of DNase activities in excretory/secretory products of infective
      larvae of Haemonchus contortus.
AB  - While multiple DNase activities occur in the excretory/secretory products (ESPs)
      of the adult Haemonchus contortus, the DNase activities in ESPs of the infective
      larvae (L3) have not been studied. Thus, the DNase activities in ESPs of H.
      contortus L3 were investigated and compared to those of adults for developmental
      stage-specific analysis. The DNase activities had relative molecular masses (M
      rs) of 34 and 36 kDa upon zymographic analysis at pH 5.0 and 7.0 when the larvae
      were incubated for over 48 h. The 34 and 36 kDa DNases of L3 ESPs were also
      detected in adult ESPs with similar characteristics. However, the 37 and 38.5 kDa
      DNases of the adult ESPs were not detected in the L3 ESPs. Since the 37 and 38.5
      kDa DNase activities were mainly detected in adult ESPs, these activities appear
      to be specific to the adult stage whereas the other ESP DNase activities appear
      to be expressed during multiple stages of the parasite's life cycle. While the
      difference in DNase activities of L3 and adults remains obscure, the role of
      DNase in larval development should be further clarified and the identification of
      stage-specific developmental markers will lead to the discovery of specific
      factors that stimulate larval development.

PMID- 21875445
TI  - Secondary prevention of ischaemic cardiac events.
AB  - INTRODUCTION: Coronary artery disease is the leading cause of mortality in
      resource-rich countries, and is becoming a major cause of morbidity and mortality
      in resource-poor countries. Secondary prevention in this context is long-term
      treatment to prevent recurrent cardiac morbidity and mortality in people who have
      had either a prior acute myocardial infarction (MI) or acute coronary syndrome,
      or who are at high risk due to severe coronary artery stenoses or prior coronary
      surgical procedures. Secondary prevention in people with an acute MI or acute
      coronary syndrome within the past 6 months is not included. METHODS AND OUTCOMES:
      We conducted a systematic review and aimed to answer the following clinical
      questions: What are the effects of antithrombotic treatment; other drug
      treatments; cholesterol reduction; blood pressure reduction; non-drug treatments;
      and revascularisation procedures? We searched: Medline, Embase, The Cochrane
      Library, and other important databases up to May 2010 (Clinical Evidence reviews
      are updated periodically, please check our website for the most up-to-date
      version of this review). We included harms alerts from relevant organisations
      such as the US Food and Drug Administration (FDA) and the UK Medicines and
      Healthcare products Regulatory Agency (MHRA). RESULTS: We found 137 systematic
      reviews or RCTs that met our inclusion criteria. We performed a GRADE evaluation
      of the quality of evidence for interventions. CONCLUSIONS: In this systematic
      review, we present information relating to the effectiveness and safety of the
      following interventions: advice to eat less fat, advice to eat more fibre, advice
      to increase consumption of fish oils, amiodarone, angiotensin-converting enzyme
      (ACE) inhibitors, angiotensin II receptor blockers, angiotensin II receptor
      blockers plus ACE inhibitors, antioxidant vitamin combinations, antiplatelet
      agents, aspirin, beta-blockers, beta-carotene, blood pressure reduction, calcium
      channel blockers, cardiac rehabilitation including exercise, class I
      antiarrhythmic agents, coronary artery bypass grafting (CABG), fibrates, hormone
      replacement therapy (HRT), Mediterranean diet, multivitamins, non-specific
      cholesterol reduction, oral anticoagulants, oral glycoprotein IIb/IIIa receptor
      inhibitors, percutaneous coronary intervention (PCI), psychosocial treatment,
      smoking cessation, statins, vitamin C, and vitamin E.

PMID- 21875447
TI  - Helminth parasites of the oceanic horse mackerel Trachurus picturatus Bowdich
      1825 (Pisces: Carangidae) from Madeira Island, Atlantic Ocean, Portugal.
AB  - The helminth parasite fauna of the oceanic horse mackerel Trachurus picturatus
      Bowdich 1825, caught off the Madeira Islands was composed of six different taxa.
      Prevalence and abundance of larval Anisakis sp. (Nematoda: Anisakidae) and
      Nybelinia lingualis (Trypanorhyncha: Tentaculariidae), the most common parasite
      taxa, were 24.3%, 0.9 and 37.9%, 0.7, respectively. Bolbosoma vasculosum
      (Acanthocephala: Polymorphidae) and the monogeneans Heteraxinoides atlanticus
      (Monogenea: Heteraxinidae) and Pseudaxine trachuri (Monogenea: Gastrocotylidae)
      were comparatively rare. The depauperate helminth fauna of the oceanic horse
      mackerel at Madeira compared to other geographical regions of the north-eastern
      Atlantic, namely the Azores banks and the West African coast, may be attributed
      to the paucity of nutrients off oceanic islands and to a low density of the fish
      population.

PMID- 21875448
TI  - Effect of the level and type of starchy concentrate on tissue lipid metabolism,
      gene expression and milk fatty acid secretion in Alpine goats receiving a diet
      rich in sunflower-seed oil.
AB  - The potential benefits on human health have prompted an interest in developing
      nutritional strategies for reducing saturated and increasing specific unsaturated
      fatty acids (FA) in ruminant milk. The impact of the level and type of starchy
      concentrate added to diets supplemented with sunflower-seed oil on caprine milk
      FA composition and on mammary, omental and perirenal adipose, and liver lipid
      metabolism was examined in fourteen Alpine goats in a replicated 3 * 3 Latin
      square with 21 d experimental periods. Treatments were a grass hay-based diet
      with a high level of forage (F) or a high level of concentrate with either maize
      grain (CM) or flattened wheat (CW) as source of starch and supplemented with 130
      g/d sunflower-seed oil. Milk yield was enhanced (P<0.01) and milk fat content was
      decreased on the CM and CW diets compared with the F diet, resulting in similar
      milk fat secretion. Both high-concentrate diets increased (P<0.05) milk yield of
      10 : 0-16 : 0 and decreased trans-9,11-18 : 1 and cis-9, trans-11-18 : 2. The CW
      diet decreased (P<0.05) the output of SigmaC18 and Sigmacis-18 : 1 and increased
      (P<0.05) the output of trans-10-18 : 1 in milk. The expression and/or activity of
      fourteen proteins involved in the major lipogenic pathways in mammary tissues and
      of lipogenic genes in adipose and liver tissues were similar among treatments. In
      conclusion, high starch concentrates alter milk FA yield via mechanisms
      independent of changes in mammary, liver or adipose tissue lipogenic gene
      expression. Furthermore, data provided indications that mammary lipogenic
      responses to starch-rich diets differ between caprine and bovine ruminants.

PMID- 21875449
TI  - Novel HPV-6 variants of human papillomavirus causing recurrent respiratory
      papillomatosis in southern Africa.
AB  - There is currently no information regarding the genetic diversity of HPV-6
      variants circulating in South Africa. The aim of this study was to determine the
      HPV-6 variants affecting patients with recurrent respiratory papillomatosis, to
      determine whether mutations correlate with disease severity and identify
      molecular determinants of virulence with prognostic relevance. HPV-6 variants
      were identified based on genome changes within the 712-991 bp region encompassing
      the non-coding region (URR) of the genome, with variations in length resulting
      from insertions and duplications, and the 453-bp gene encoding the E6 protein.
      Based on manual comparison of sequence data from the URR, the isolates were
      identified as HPV-6a and HPV-6vc variants. Three novel HPV-6 variants were
      identified: one based on a mutation in the E6 region; two based on changes in the
      URR including a unique substitution detected in three isolates and an insertion
      and 170-bp duplication in the URR genome in one patient, who had clinical
      features of severe disease.

PMID- 21875450
TI  - Incidence of childhood pneumonia and serotype and sequence-type distribution in
      Streptococcus pneumoniae isolates in Japan.
AB  - The 7-valent pneumococcal conjugate vaccine (PCV7) is reported to decrease the
      incidence of community-acquired pneumonia (CAP) in children. To determine the
      annual incidence of CAP before the introduction of PCV7, we counted the number of
      children hospitalized with CAP between 2008 and 2009 in Chiba City, Japan. We
      investigated serotype and multilocus sequence typing (MLST) for Streptococcus
      pneumoniae isolates in CAP cases. The annual incidence of hospitalized CAP in
      children aged <5 years was 17.6 episodes/1000 child-years. In 626 episodes, S.
      pneumoniae was dominant in 14.7% and 0.8% of sputum and blood samples,
      respectively. The most common serotypes were 6B, 23F and 19F. The coverage rates
      of PCV7 were 66.7% and 80% in sputum samples and blood samples, respectively.
      MLST analysis revealed 37 sequence types. Furthermore, 54.1% of the sputum
      isolates and 40% of the blood isolate were related to international multidrug
      resistant clones.

PMID- 21875451
TI  - A large outbreak of scombroid fish poisoning associated with eating yellowfin
      tuna (Thunnus albacares) at a military mass catering in Dakar, Senegal.
AB  - On 26 November 2010, an outbreak of scombroid fish poisoning occurred in the
      French Armed Forces in Dakar, Senegal. This chemical intoxication, due to high
      histamine concentration in fish, is often mistaken for an allergic reaction. A
      case-control study was undertaken including the 71 cases and 78 randomly selected
      controls among lunch attendees. The usual symptoms for scombroid fish poisoning
      were observed in cases, i.e. flushing (85.9%), headache (83.1%), rapid/weak pulse
      (59.1%) and diarrhoea (47.9%). Symptoms occurred from within a few minutes to up
      to 3 h following the meal. Most patients quickly recovered with antihistamine
      and/or symptomatic treatment. Tuna was the only food item positively associated
      with illness (odds ratio 36.3, 95% confidence interval 6.3-210.0), with the risk
      of illness increasing with the quantity of fish consumed. No bacterial
      contamination was found in leftover food, but histamine concentration in tuna was
      found to be 4900 mg/kg, almost 50-fold higher than the concentration allowed by
      European regulations. This report is unique because of the large size of the case
      series - to our knowledge, the largest event of scombroid fish poisoning ever
      reported - and the chemical and bacteriological analyses results obtained on
      leftover food.

PMID- 21875452
TI  - Analysis of overdispersed count data: application to the Human Papillomavirus
      Infection in Men (HIM) Study.
AB  - The Poisson model can be applied to the count of events occurring within a
      specific time period. The main feature of the Poisson model is the assumption
      that the mean and variance of the count data are equal. However, this equal mean
      variance relationship rarely occurs in observational data. In most cases, the
      observed variance is larger than the assumed variance, which is called
      overdispersion. Further, when the observed data involve excessive zero counts,
      the problem of overdispersion results in underestimating the variance of the
      estimated parameter, and thus produces a misleading conclusion. We illustrated
      the use of four models for overdispersed count data that may be attributed to
      excessive zeros. These are Poisson, negative binomial, zero-inflated Poisson and
      zero-inflated negative binomial models. The example data in this article deal
      with the number of incidents involving human papillomavirus infection. The four
      models resulted in differing statistical inferences. The Poisson model, which is
      widely used in epidemiology research, underestimated the standard errors and
      overstated the significance of some covariates.

PMID- 21875453
TI  - Outbreak of Neisseria meningitidis C in workers at a large food-processing plant
      in Brazil: challenges of controlling disease spread to the larger community.
AB  - SUMMARYAn outbreak of meningococcal disease (MD) with severe morbidity and
      mortality was investigated in midwestern Brazil in order to identify control
      measures. A MD case was defined as isolation of Neisseria meningitidis, or
      detection of polysaccharide antigen in a sterile site, or presence of clinical
      purpura fulminans, or an epidemiological link with a laboratory-confirmed case
      patient, between June and August 2008. In 8 out of 16 MD cases studied, serogroup
      C ST103 complex was identified. Five (31%) cases had neurological findings and
      five (31%) died. The attack rate was 12 cases/100 000 town residents and 60
      cases/100 000 employees in a large local food-processing plant. We conducted a
      matched case-control study of eight primary laboratory-confirmed cases (1:4).
      Factors associated with illness in single variable analysis were work at the
      processing plant [matched odds ratio (mOR) 22, 95% confidence interval (CI) 2.3
      207.7, P<0.01], and residing <1 year in Rio Verde (mOR 7, 95% CI 1.11-43.9,
      P<0.02). Mass vaccination (>10 000 plant employees) stopped propagation in the
      plant, but not in the larger community.

PMID- 21875454
TI  - The association between body shape silhouette and dietary pattern among Mexican
      women.
AB  - OBJECTIVE: To investigate the relationship between dietary patterns and self
      perceived body shape silhouette and BMI in a sample of Mexican women. DESIGN: A
      cross-sectional analysis of dietary habits from baseline data of a large cohort
      study (EsMaestra) conducted in 2006-2008. SETTING: The state of Veracruz, Mexico.
      SUBJECTS: Mexican teachers (n 20 330) provided information on body shape
      silhouette at baseline, changes in body shape silhouette and BMI, as well as
      information on sociodemographic variables and lifestyle. RESULTS: The median BMI
      was 26.8 kg/m2; 43 % of women were overweight and 24 % were obese. The
      carbohydrates, sweet drinks and refined foods pattern was associated with a
      greater risk of having a large silhouette and a large BMI (BMI >= 30.0 kg/m2 v.
      BMI < 25.0 kg/m2; ORT1-3 = 1.86, 95 % CI 1.56, 2.22 and 1.47, 95 % CI 1.28, 1.69,
      respectively) with a significant trend when comparing the first and third
      tertiles of intake. The fruit and vegetable pattern was associated with a lower
      risk of having a large silhouette and a large BMI (ORT1-3 = 0.68, 95 % CI 0.57,
      0.82 and ORT1-3 = 0.77, 95 % CI 0.67, 0.88, respectively) with a significant
      decreasing trend. Similar results were observed when change in silhouette (from
      18 years of age to current silhouette) was considered. CONCLUSIONS: High intakes
      of carbohydrates, sweet drinks and refined foods are related to larger
      silhouettes. Public health intervention improving access to healthy dietary
      guidelines, healthy food choice in the work place, promotion of physical activity
      and regulation of beverages with a high sugar content and of refined foods should
      be considered.

PMID- 21875455
TI  - The brain-derived neurotrophic factor gene in suicidal behaviour: a meta
      analysis.
AB  - Suicide is a prominent public health problem. Its aetiology is complex, and the
      brain-derived neurotrophic factor (BDNF) has been implicated. We performed the
      first meta-analysis of the functional BDNF marker Val66Met (rs6265, 196G>A) in
      suicidal behaviour using data from 11 previously published samples plus our
      present sample (total n=3352 subjects, 1202 with history of suicidal behaviour.
      The meta-analysis including all 12 studies showed a trend for the Met-carrying
      genotypes and Met allele conferring risk for suicide (random-effects model
      p=0.096; ORMet-carrier=1.13, 95% CI 0.98-1.30, and random-effects model p=0.032;
      ORMet=1.16, 95% CI 1.01-1.32, respectively). Furthermore, we found the Met allele
      and the Met allele-carrying genotypes to be associated with history of suicide
      attempt (eight studies; allelic meta-analysis--random-effects model: p=0.013;
      fixed-effects model: p=0.006; genotypic meta-analysis--random-effects model:
      p=0.017; fixed-effects model: p=0.008). Taken together, the results from our
      study suggest that BDNF Val66Met is involved in suicidality. Further studies are
      required to elucidate its role in suicidal behaviour.

PMID- 21875456
TI  - Spatial mapping of hepatitis C prevalence in recent injecting drug users in
      contact with services.
AB  - In developed countries the majority of hepatitis C virus (HCV) infections occur
      in injecting drug users (IDUs) with prevalence in IDUs often high, but with wide
      geographical differences within countries. Estimates of local prevalence are
      needed for planning services for IDUs, but it is not practical to conduct HCV
      seroprevalence surveys in all areas. In this study survey data from IDUs
      attending specialist services were collected in 52/149 sites in England between
      2006 and 2008. Spatially correlated random-effects models were used to estimate
      HCV prevalence for all sites, using auxiliary data to aid prediction. Estimates
      ranged from 14% to 82%, with larger cities, London and the North West having the
      highest HCV prevalence. The methods used generated robust estimates for each
      area, with a well-identified spatial pattern that improved predictions. Such
      models may be of use in other areas of study where surveillance data are sparse.

PMID- 21875457
TI  - [Progress in research on epigenetics of cancer stem cells].

PMID- 21875458
TI  - [Effect of semaphorin4D gene silencing on malignant behavior of human ovarian
      cancer SKOV3 cells].
AB  - OBJECTIVE: To observe the effect of DNA Sema4D gene silencing by RNA interfering
      on the proliferation, migration and invasion of human ovarian cancer SKOV3 cells,
      and to study the effect of pshRNASema4D on the growth of SKOV3 cells in
      transplanted tumor in nude mice. METHODS: Recombinant plasmid pshRNASema4D-A, B
      and C were respectively transfected into SKOV3 cells by lipofetamine 2000, while
      cells transfected by plasmid vector pcDNA3.1 and cells untreated as control
      groups. RT-PCR was adopted to select the recombinant plasmid which showed the
      most optimal inhibition effect. RT-PCR and Western blot were used to detected the
      mRNA and protein expression of Sema4D in SKOV3 cells tranfected for 24, 48 and 72
      hours. MTT assay was used to investigate the proliferation of the SKOV3 cells
      after trasnsfection. Transwell cell migration and invasion assays were used to
      investigate the migration and invasion abilities of the SKOV3 cells after
      trasnsfection. Human ovarian cancer model was established in nude mice, and the
      nude mice were treated with pshRNASema4D-B once every 3 days for 3 weeks. The
      bulk of the transplanted tumor was measured. RESULTS: Three Sema4D-targeted short
      hairpin RNA (shRNA) A, B and C were successfully inserted into the plasmid vector
      pshRNA, and the coding sequences of the obtained shRNA were consistent with the
      designed fragment. The results indicated that both recombinant plasmid
      pshRNASema4D-A and B could effectively knock down the expression of Sema4D gene
      in human ovarian cancer cells, of which pshRNASema4D-B was the better choice,
      while no effect of pshRNASema4D-C was seen. RT-PCR results showed that the
      relative mRNA expression of Sema4D gene in SKOV3 cells transfected with pshRNA
      Sema4D for 24, 48 and 72 hours were 0.401 +/- 0.051, 0.120 +/- 0.035 and 0.014 +/
      0.015, respectively, which were significantly lower than that in SKOV3 cells
      transfected by empty vector and non-transfected cells at 72 hours after
      transfection. (0.521 +/- 0.019, 0.536 +/- 0.040,respectively, P < 0.05). The
      Westen blot analysis manifested that the relative expression of Sema4D protein of
      SKOV3 cells transfected by pshRNASema4D for 24, 48 and 72 hours were 0.196 +/-
      0.023, 0.074 +/- 0.015 and 0.040 +/- 0.014, respectively, which were
      significantly lower than that in SKOV3 cells transfected by empty vector and non
      transfected cells at 72 hours after transfection. (0.275 +/- 0.009, 0.282 +/-
      0.015, respectively, P < 0.05). Comparing with the empty vector-transfected and
      non-transfected cells, the proliferation, invasion and migration ability of SKOV3
      cells transfected with pshRNA-Sema4D were obviously weakened. The pshRNASema4D-B
      significantly suppressed the growth of the SKOV3 cells-transplanted tumors in
      nude mice, and the IR (inhibitory rate) of pshRNASema 4D-B group was (61.0 +/-
      3.3)% (P < 0.05). CONCLUSIONS: Sema4D can be successfully silenced by RNA
      interfering in human ovarian cancer SKOV3 cells. Downregulation of Sema4D can
      inhibit the proliferation, migration and invasion of ovarian cancer cells. The
      pshRNASema4D can significantly suppress the growth in transplanted tumor of human
      ovary cancer in nude mice. Sema4D may become a candidate gene of gene therapy of
      human ovarian cancer.

PMID- 21875459
TI  - [Effect of lysyl oxidase on migration and adhesion of human gastric cancer HGC-27
      cells in vitro].
AB  - OBJECTIVE: To study the effects of lysyl oxidase (LOX) on the migration and
      adhesion of the human gastric cancer cell line HGC-27 cells in vitro. METHODS:
      The human gastric cancer cell line HGC-27 cells were cultured in vitro, and
      treated with different concentration of beta-aminopropionitrile (BAPN). The
      ability of migration was assessed by wound-healing assay. The ability of adhesion
      was detected by homogenous and heterogeneous adhesion experiments. RESULTS:
      Compared that with 0 mmol/L BAPN, the ability of migration of the cells after
      treatment with 0.2 mmol/L BAPN was descended at 8, 24, 32 and 48 h; the number of
      cells with homogeneous adhesion was increased from (6.97 +/- 0.07) * 10(3)/ml to
      (7.78 +/- 0.11) * 10(3)/ml; and the number of cells with heterogeneous adhesion
      was decreased from (8.98 +/- 0.15) * 10(3)/ml to (8.35 +/- 0.10) * 10(3)/ml, both
      < 0.05. Compared with that of cells treated with 0 mmol/L and 0.2 mmol/L BAPN,
      the migration ability of cells after treatment with 0.3 mmol/L BAPN was descended
      at 8, 24, 32 and 48 h; the number of cells with homogeneous adhesion was raised
      to (8.02 +/- 0.11) * 10(3)/ml and the number of cells with heterogeneous adhesion
      was down to (7.93 +/- 0.07) * 10(3)/ml (P < 0.05). CONCLUSION: LOX may promote
      the metastasis of cancer cells by enhancing invasion, increasing heterogeneous
      adhesion and decreasing homogeneous adhesion.

PMID- 21875460
TI  - [Effects of mTOR siRNA on mTOR/p70S6K signaling pathway in esophageal squamous
      cell carcinoma cells and the growth of transplanted tumor in nude mice].
AB  - OBJECTIVE: To investigate the effects of mTOR siRNA on mTOR-p70S6K signaling
      pathway in esophageal squamous cell carcinoma (ESCC) cells in vitro,and growth
      and apoptosis in transplanted tumor in nude mice. METHODS: mTOR siRNA was
      transfected into ESCC cell line EC9706 cells. The expressions of factors of the
      mTOR/p70S6K signaling pathway were detected by RT-PCR and Western blot. DNA
      contents and cell apoptosis were determined by flow cytometry, and cell
      proliferation was measured by CCK-8 assay. The effects of mTOR siRNA on the
      transplanted tumor growth were assessed in nude mice. RESULTS: The levels of mTOR
      and p-p70S6K were significantly decreased (P < 0.05) while the level of p70S6K
      was increased (P < 0.05) in the cells transfected with mTOR siRNA, compared with
      that in untransfected cells and cells transfected with control siRNA. After being
      interfered by mTOR siRNA, the number of apoptotic cells was increased, cell
      proliferation became slower and cell cycle was arrested in G(1) phase compared
      with that in control cells. Also, mTOR siRNA inhibited the growth of transplanted
      tumor in vivo. CONCLUSIONS: mTOR siRNA can effectively interfere in mTOR-p70S6K
      signaling pathway, induce cell apoptosis and inhibit cell proliferation and tumor
      growth, suggesting that mTOR-p70S6K signaling pathway plays an important role in
      the carcinogenesis and development of esophageal squamous cell carcinoma.

PMID- 21875461
TI  - [FAK/c-Src signaling pathway mediates the expression of cell surface HSP90 in
      cultured human prostate cancer cells and its association with their invasive
      capability].
AB  - OBJECTIVE: To investigate the expression of heat shock protein 90 (HSP90) on the
      cell surface of highly invasive human prostate cancer cells PC3 and its possible
      molecular mechanisms of its effect on cell invasion through analyzing FAK/Src
      signaling pathway. METHODS: The expression of cell surface HSP90 on PC3 cells was
      studied by immunofluorescence staining and surface biotinylation assay
      respectively. A specific HSP90 antibody was used to inhibit the cell surface
      HSP90. In vitro cell invasion was assessed by modified Boyden chambers.
      Phosphorylated FAK on tyr 397, 576, 577 and 925, and phosphorylated c-Src on tyr
      416 were examined by Western blot assay. The association between FAK and c-Src
      was analyzed by immunoprecipitation. The effects of FAK knockdown by siRNA or Src
      kinases inhibitor PP2, with or without anti-HSP90 antibody, on PC3 cell invasion
      were also evaluated. RESULTS: A pool of HSP90 was detected on the cell surface of
      PC3 cells. A specific HSP90 antibody significantly retarded tumor cell invasion.
      Concomitant with this finding, targeting cell surface HSP90 significantly
      inhibited the phosphorylations of FAK and c-Src, and also the interactions
      between FAK and c-Src. FAK knockdown or PP2 dramatically suppressed cell
      invasion, however, anti-HSP90 antibody didn't further inhibit cell invasion.
      CONCLUSIONS: Cell surface HSP90 promotes human prostate cancer cell invasion
      through a FAK/c-Src signaling, with may be a novel therapeutic target against
      metastatic tumors.

PMID- 21875462
TI  - [Mechanism of apoptosis in human leukemia NB4 cells induced by total
      astragalosides].
AB  - OBJECTIVE: To investigate the effect of total astragalosides (TA) on
      proliferation and apoptosis in human leukemia NB4 cells in vitro. METHODS: The
      NB4 cells were treated with TA at different concentrations for 48 h in culture.
      Growth inhibition rates were measured by CCK-8 method. Flow cytometry was used to
      explore the cell apoptosis and the activity of NF-kappaB and Akt during
      apoptosis. RESULTS: TA at different concentrations (200, 400, 600, 800 mg/L)
      inhibited proliferation of NB4 cells in a dose-dependent manner (P < 0.05), and
      the inhibitory rates of TA on NB4 cells were (14.54 +/- 3.20)%, (24.79 +/-
      3.98)%, (57.28 +/- 4.71)% and (88.28 +/- 4.65)%, respectively. In terms of the
      induction of apoptosis, there was a significant difference between the TA group
      and blank control [(1.80 +/- 1.24)%, P < 0.05]. At TA doses of 200, 400 and 600
      mg/L, the apoptotic rates of NB4 cells were (10.03 +/- 3.31)%, (14.87 +/- 3.65)%,
      (23.45 +/- 1.90)%, respectively. Besides, TA induced apoptosis of NB4 cells in a
      dose-dependent manner in the groups of 200 mg/L, 400 mg/L, 600 mg/L (P < 0.05).
      But there was no significant difference in apoptotic rates between the groups of
      800 mg/L and 600 mg/L [(23.45 +/- 1.90)%, P > 0.05]. In the group of 800 mg/L,
      the necrotic cells increased highly and the necrotic rate reached (45.65 +/-
      3.16)%. After TA treatment of NB4 cells at different concentrations (200, 400,
      600 mg/L), the expression of NF-kappaB protein was significantly decreased
      compared with that of the blank control (9.79 +/- 0.95, P < 0.05), while Akt
      protein was not significantly decreased (P > 0.05). CONCLUSION: TA can inhibit
      the growth of NB4 cells and induce apoptosis in NB4 cells through an Akt
      independent NF-kappaB signaling pathway.

PMID- 21875463
TI  - [Reversal effect of 5-Aza-dc on cisplatin-resistance in human NSCLC cells in
      vitro].
AB  - OBJECTIVE: The aim of this study was to investigate the effect of 5-aza-2'
      deoxycytidine (5-Aza-dc), a methylation inhibitor, on cisplatin-resistance in non
      small cell lung cancer cell line A549/DDP and to explore its possible mechanism.
      METHODS: MTT assay was used to test the cytotoxicity of 5-Aza-dc on A549/DDP
      cells, and the IC(50) and cisplatin resistance index of A540/DDP cells at 48
      hours after 5-Aza-dc (0 umol/L, 20 umol/L, 40 umol/L) treatment at different
      concentrations. MSP, fluorescence quantitative RT-PCR (real-time RT-PCR) and
      Western blot were used to detect the hMLH1 methylation status, mRNA and protein
      expressions, respectively. RESULTS: The IC(50) value of cisplatin in A549/DDP
      cells was 30.15 +/- 0.76 umol/L. The MTT assay results demonstrated that during
      the 5-Aza-dc treatment for 48 hours, the dose of 20 umol/L was non-toxic and 40
      umol/L was low-toxic. 5-Aza-dc at those two doses reduced IC(50) value of
      cisplatin to 16.54 +/- 0.35 umol/L (RI = 1.82) and 6.82 +/- 0.16 umol/L (RI =
      4.42), respectively. MSP, real-time RT-PCR and Western blot showed that 5-Aza-dc
      at non-toxic and low-toxic doses removed the partial hMLH1-hypermethylation, and
      up-regulated hMLH1 mRNA and protein expressions. CONCLUSIONS: Low dose 5-Aza-dc
      can partially reverse the cisplatin-resistance in A549/DDP cells, which may be
      achieved through removal of hMLH1 hypermethylation and increased expression of
      hMLH1 gene. 5-Aza-dc may have a role in increasing the efficacy of chemotherapy
      for patients whose tumors are lack of hMLH1 expression because of hMLH1 promoter
      hypermethylation.

PMID- 21875464
TI  - [Expression of BRAF V600E mutation in different thyroid lesions].
AB  - OBJECTIVE: To evaluate the expression of BRAF V600E mutation in 240 Chinese
      patients with thyroid lesions. METHODS: Two hundred and forty Chinese patients
      with thyroid lesions, including 129 papillary thyroid carcinomas (PTC), 12
      follicular carcinomas, 4 medullary carcinomas, 30 adenomas, 30 nodular goiters,
      and 35 papillary hyperplasia. DNA was extracted from thyroid biopsy and paraffin
      embedded thyroid tissues, and the expression of BRAF V600E mutation was detected
      by polymerase chain reaction and DNA sequencing assays. RESULTS: The presence of
      BRAF V600E mutation was found in 61 of the total group of 240 cases (25.4%). It
      was only detected in PTC (47.3%), and not detected in other types of malignant
      and benign thyroid lesions. There was a statistically significant difference
      between the expression of BRAF V600E mutation in classic type PTC (49.6%) and in
      follicular type PTC (12.5%,P < 0.05), but statistical data did not show any
      correlation between BRAF V600E mutation and clinicopathologic parameters in PTC
      (P > 0.05). CONCLUSIONS: BRAF V600E mutation has a significant correlation with
      PTC and the detection of BRAF V600E mutation may be used as an important
      prognostic marker of PTC. Our new method of DNA extraction from paraffin embedded
      tissues is efficient and inexpensive.

PMID- 21875465
TI  - [Expression of Raf kinase inhibitor protein and its significance in invasion and
      metastasis of hepatocellular carcinoma].
AB  - OBJECTIVE: To investigate the expression of RKIP, p65 and pERK in hepatocellular
      carcinoma (HCC) and theIr correlation with invasion and metastasis of HCC.
      METHODS: Reverse transcription polymerase chain reaction (RT-PCR) was used to
      detect the expression of RKIP mRNA. The expression levels of RKIP, p65 and pERK
      proteins in HCC tumor and peritumoral tissues were determined by
      immunohistochemistry and Western blot analysis. Statistical analysis was
      performed to determine the relationship between their expression and
      clinicopathological parameters. RESULTS: RKIP protein expression level
      (RKIP/actin) was 0.579 +/- 0.380 in HCCs, 1.178 +/- 0.659 in peritumoral tissues
      and 1.115 +/- 0.442 in normal liver tissues. The pERK protein level was 1.023 +/-
      0.478, 0.605 +/- 0.367 and 0.461 +/- 0.293, p65 protein level was 0.83 +/- 0.376,
      0.63 +/- 0.337 and 0.466 +/- 0.345, respectively. Immunohistochemistry analysis
      showed that the RKIP positive rates in HCCs, peritumoral tissues and normal liver
      tissues, were 22.2%, 86.0%, and 93.8%, positive rates of p65 were 73.6%, 56.0%
      and 37.5%, positive rates of pERK were 65.3%, 38.0% and 31.3%, respectively.
      Statistical analysis revealed that there was a significant difference in RKIP
      protein expression levels (P < 0.05), but no significant difference in RKIP mRNA
      expression levels (P > 0.05) among HCC tumors, peritumoral tissues and normal
      liver tissues. The p65-positive and pERK-positive rates were higher in tumor
      tissues than that in peritumoral tissues and in normal liver tissues (P < 0.05),
      but RKIP-positive rates were lower in tumor tissues than that in paritumoral
      tissues and normal liver tissues (P < 0.05). RKIP protein expression levels were
      significantly lower in HCCs with intrahepatic or lymphatic metastasis than that
      in without. The RKIP positive rates in moderately and well differentiated HCCs
      were significantly higher than that in poorly differentiated HCCs. There was a
      relationship between RKIP and pERK expressions (P = 0.04), but RKIP expression
      was not correlated with p65 expression in HCCs (P = 0.143). CONCLUSIONS: Our
      findings indicate that the down-regulation of RKIP expression may serve as a
      predictive marker for HCC development, progression and metastasis, which may
      contribute to the elevated ERK activity. The inhibiting effect of RKIP on
      invasion and metastasis of liver cancer cells may be due to the down-regulation
      of pERK expression rather than p65 expression.

PMID- 21875466
TI  - [Correlation of TOP2A gene expression and survival of breast cancer patients].
AB  - OBJECTIVE: The aim of this study was to assess the TOP2A RNA expression and the
      relationship of TOP2A protein expression with metastasis-free interval in breast
      cancer patients. METHODS: TOP2A expression was analyzed prior to surgery in 86
      patients. The level of TOP2A gene amplification was analyzed by fluorescence in
      situ hybridization (FISH), its RNA expression level with RT-PCR, and their
      correlation with TOP2A protein expression was assessed by immunohistochemistry
      (IHC). The correlation between RNA expression level and metastasis-free interval
      in breast cancer patients was also analyzed. RESULTS: Aberrations (amplification
      or deletion) of TOP2A copy number was observed in 25.6% (22/86) of the cases.
      TOP2A protein expression was detected in 66.3% (57/86) of the samples. There was
      a significant correlation between the TOP2A RNA expression and protein expression
      (P < 0.001). TOP2A gene expression was significantly associated with the
      metastasis-free interval in the breast cancer patients (P = 0.001). There was no
      significant correlation between TOP2A gene amplification and TOP2A protein
      expression (P = 0.211). CONCLUSIONS: TOP2A RNA level is an objective and reliable
      prognostic indicator in breast cancer.

PMID- 21875467
TI  - [Prognostic value of CYFRA 21-1 and CEA in patients with undifferentiated
      nasopharyngeal carcinoma before and after radiotherapy].
AB  - OBJECTIVE: The purpose of this study was to evaluate the potential of CYFRA 21-1
      (CYFRA) and CEA as a prognostic marker in patients with undifferentiated
      nasopharyngeal carcinoma (NPC). METHODS: From March 2004 to February 2008, 62
      patients with newly diagnosed, undifferentiated NPC were treated in our
      department. Their clinocopathological data were analyzed retrospectively. All
      patients received intensity-modulated radiotherapy using 6 MV X-rays, and serum
      CYFRA and CEA before and after radiotherapy were assayed. The association among
      the long-term follow-up results and age, sex, smoke, TNM stage, chemotherapy,
      CEA, CYFRA and the changes in any direction of serum CYFRA and CEA were
      determined. RESULTS: Patients with low pre-RT level (<= 2.49 ug/L) of CYFRA had a
      significantly better overall survival (OS) than patients with high level (> 2.49
      ug/L,OR = 8.555, P = 0.029). N classification and T classification were
      positively associated with the prediction of progression free survival (OR =
      4.054, P = 0.001;OR = 3.873, P = 0.001). But there was no significant association
      between the rest predictors (age, sex, CEA, post-RT CYFRA, chemotherapy and a
      radiation-induced decrease in serum markers) and the survival or recurrence rate
      by multivariate analysis. CONCLUSIONS: The results of the present study show that
      pre-RT serum CYFRA level is a valuable factor for predicting long-term survival
      in patients with undifferentiated nasopharyngeal carcinoma. More aggressive
      treatment may be given to those patients with a high serum CYFRA level.

PMID- 21875468
TI  - [Expression of ERCC1 mRNA and its impact on the prognosis of patients with non
      small cell lung cancer].
AB  - OBJECTIVE: To investigate the level of ERCC1 mRNA expression in non-small cell
      lung cancer and analyze the influencing factors of the survival of patients after
      operation. METHODS: The level of ERCC1 mRNA expression was quantified in sixty
      pairs of non-small cell lung cancer tissue and their matched normal lung tissues
      by real-time PCR assay. The survival of patients was analyzed by univariate
      Kaplan-Meier and Cox regression analysis. RESULTS: The level of ERCC1 mRNA
      expression in cancer tissues (-7.85 +/- 3.86) was significantly higher than that
      in matched normal ones (-11.19 +/- 5.03;t = 3.973, P = 0.000). Up-regulation of
      ERCC1 mRNA was found in 43 of 60 (71.7%) lung cancer tissues compared with that
      in the matched normal lung tissues (17 of 60, 28.3%). The univariate survival
      analysis by Kaplan-Meier method showed that the survival rate of patients with
      high ERCC1 mRNA expression was lower than that in the patients with low
      expression of ERCC1 mRNA (P = 0.000). Patients with lymph node metastasis,
      smoking, cancer family history, or high pathological grade had significantly
      shorter survaival time than those without lymph node metastasis, smoking, cancer
      family history, or with low pathological grade. Cox regression survival analysis
      showed that the level of ERCC1 mRNA expression, lymph node metastasis, smoking,
      and pathological grade were significant independent factors affecting the
      survival rate. CONCLUSIONS: Non-small cell lung cancer patients with up-regulated
      ERCC1 expression have a poor survival. The expression of ERCC1 mRNA, lymph node
      metastasis, pathological grade, cancer family history and smoking can be used as
      prognostic indicator of non-small cell lung cancer.

PMID- 21875469
TI  - [Analysis of the factors related to esophageal injuries in radiotherapy of
      esophageal cancer].

PMID- 21875470
TI  - [Efficacy and safety of gefitinib or docetaxel in Chinese patients with locally
      advanced or metastatic non-small cell lung cancer (NSCLC) who had failed previous
      platinum-based first-line chemotherapy].
AB  - OBJECTIVE: To compare the efficacy and safety of gefitinib or docetaxel in
      Chinese patients with locally advanced or metastatic non-small cell lung cancer
      (NSCLC) who had failed previous platinum-based first-line chemotherapy. METHODS:
      We retrospectively reviewed 222 Chinese NSCLC patients in the subgroup of
      INTEREST (gefitinib versus docetaxel in previously treated non-small cell lung
      cancer) study. Survival analysis was evaluated by Kaplan-Meier method, and
      Functional Assessment of Cancer Therapy-Lung (FACT-L) was used to compare the
      quality of life between gefitinib group and docetaxel group. RESULTS: A total of
      222 patients were analyzed in this subgroup study. 107 patients were treated with
      gefitinib, and 115 patients treated with docetaxel. There were all balanced
      between the two groups in terms of sex, age, staging and pathology in patient
      characteristics. The median overall survival in the two groups was similar (11
      months in the gefitinib group vs. 14.0 months in the docetaxel group, P = 0.783).
      The progression-free survival (PFS) was also similar between the two groups
      (median PFS: 3.4 months in gefitinib group vs. 3.8 months in docetaxel group, P =
      0.214). The response rate in gefitinib group was significantly higher than that
      in the docetaxel group (21.9% vs. 9.1%, P = 0.016). CONCLUSION: The efficacy of
      gefitinib is similar with that of docetaxel in pretreated patients with locally
      advanced or metastatic NSCLC, however, gefitinib is more favorable in the
      tolerance and quality of life improvement.

PMID- 21875471
TI  - [Treatment outcomes and clinicopathologic characteristics of advanced triple
      negative breast cancer patients].
AB  - OBJECTIVE: To characterize the sites of distant recurrence and clinical outcomes
      in a cohort of Chinese patients with metastatic triple-negative breast cancer
      (TNBC). METHODS: One hundred and thirty-four patients with metastatic TNBC
      treated at Cancer Hospital of CAMS from January 1999 to December 2007 were
      included in this study. The clinicopathological features and long-term survival
      of the patients were retrospectively analyzed. RESULTS: The median age of the
      patients was 45 years. Most patients (72.7%) had a higher predilection for
      visceral metastasis and early recurrence within the first two years of follow-up.
      Six patients (4.5%) presented with stage IV disease, 14 patients were diagnosed
      with locoregional recurrence after mastectomy, 75 patients with distant
      metastases, and 45 patients with both locoregional recurrence and distant
      metastasis. The most common site of first recurrence was the lung, and
      62(51.7%)of the patients had more than two sites of metastasis. By July 30, 2009,
      75 patients died of breast cancer (56.0%). The median overall survival (OS) was
      26.5 months [95% confidence interval (CI), 20.5 - 32.6 months]. The 1-, 3- and 5
      year overall survivals (OS) were 80.9%,37.1% and 30.1%, respectively. The median
      overall survival time of 58 patients with single site of metastasis was 28.5
      months, longer than that of patients with more than two sites of metastases.
      Patients whose initial distant recurrence was bone metastasis only (7 patients)
      had better prognosis, with a median OS of 84.2 months. The median OS (28.5 vs.
      12.6 months, P = 0.0001) differed significantly between patients who received
      first-line chemotherapy and those who did not. Forty-five of the 96 patients with
      measurable disease achieved complete/partial response (CR/PR), 39 patients had
      stable disease (SD), and 12 patients had disease progression (PD). The median OS
      was 36.1 months in patients with CR/PR, 20.8 months with SD, and 14 months with
      PD, respectively. The median OS of patients with CR/PR was significantly longer
      than that of patients with SD/PD (P = 0.0108). Distant metastasis, first-line
      chemotherapy and clinical response were significantly related with OS by
      univariate analysis. Furthermore, first-line chemotherapy and the clinical
      response were demonstrated to be an independent prognostic factor by multivariate
      analysis. CONCLUSIONS: Recurrence risk and mortality are considerably higher in
      TNBC patients within the early years of follow-up. TNBC patients have a higher
      risk of multiple and visceral metastases, and poorer survival, which might
      attribute to its aggressive clinical behavior and lack of effective regimens. Our
      findings also suggest that chemotherapy can effectively improve the clinical
      outcome of those patients.

PMID- 21875472
TI  - [Evaluation of the efficacy and safety of intravesical instillation with
      gemcitabine after first-line intravesical chemotherapy failure in the treatment
      of non-muscle-invasive bladder cancer].
AB  - OBJECTIVE: To evaluate the efficacy and safety of intravesical instillation with
      gemcitabine after first-line intravesical chemotherapy failure, including
      mitomycin (MMC), epirubicin (EPB) and camptothecin (CPT), in the treatment of non
      muscle-invasive bladder cancer (NMIBC). METHODS: From June 2007 to October 2008,
      72 patients with NMIBC, who had tumor recurrence within one year of first-line
      intravesical chemotherapy, were assigned to 3 groups (24 cases each). Group A
      received intravesical gemcitabine in a dose of 1000 mg, Group B received 2000 mg
      gemcitabine, and Group C received original intravesical chemotherapy. The time of
      reccurrence and adverse effects were recorded. RESULTS: The 2-year tumor free
      survival rates of the 3 groups were 66.7%, 75.0% and 45.8%, respectively. The 2
      year TFS rate of the patients who received gemcitabine was 70.8%, significantly
      higher than 45.8% of the patients treated by original chemotherapy. There was one
      case with renal function impairement in the groups A and B, respectively. There
      was no significant difference between the rates of low urinary tract symptoms in
      the 3 groups. No severe hematological side effects were observed in this study.
      CONCLUSION: The intravescal chemotherapy with gemcitabine in patients with
      recurrent bladder tumor after first-line intravesical chemotherapy is effective
      and well tolerated, however, renal function should be routinely assessed.

PMID- 21875473
TI  - [Efficacy and side effects of combination therapy of oxaliplatin and S-1 for
      colorectal cancer].
AB  - OBJECTIVE: To observe the efficacy and side effects of the combination therapy of
      oxaliplatin and S-1 in treating postoperative colorectal cancer patients.
      METHODS: 54 postoperative colorectal cancer patients received the combination
      therapy of oxaliplatin and S-1 regimen, repeated every 3 weeks, and evaluate the
      efficacy after 3 cycles. RESULTS: All of the 54 patients but 2 (changed the
      chemotherapy regimen after the first cycle because of economic reason) finished 6
      cycles of the chemotherapy treatment. There were 6 cases (11.5%) with complete
      response (CR), 28 cases (53.8%) with partial response (PR), and the overall
      response rate was 65.4%. Major adverse effects were hematological toxicities,
      gastrointestinal disturbance, neurosensory toxicity. There were no chemotherapy
      related deaths. CONCLUSIONS: Oxaliplatin combined with S-1 is an effective and
      better tolerated chemotherapy treatment for postoperative colorectal cancer
      patients, with no serious side effects for liver and kidney. Therefore, it can be
      used as an alternative chemotherapy regimen for postoperative colorectal cancer
      patients.

PMID- 21875474
TI  - [Efficacy of Yanshu injection (a compound Chinese traditional medicine) combined
      with concurrent radiochemotherapy in patients with stage III nasopharyngeal
      carcinoma].
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of Yanshu injection (a compound
      Chinese traditional medicine from Sophora flauescens Ait) combined with
      concomitant radiochemotherapy in patients with stage III nasopharyngeal
      carcinoma. METHODS: Sixty patients with stage III nasopharyngeal carcinoma were
      randomized into Yanshu group and control group (n = 30, each). Patients in the
      Yanshu group received Yanshu injection in addition to intensity modulated
      radiation therapy (IMRT) and concomitant chemotherapy, and those in the control
      group were treated with IMRT and concurrent chemotherapy. RESULTS: The 1-year, 2
      year, 3-year and 4-year overall survival rates were 100%, 93.3%, 86.7%, 80.0% for
      Yanshu group, and 96.7%, 90.0%, 83.3%, 76.7% for the control group, respectively,
      with no significant difference between the two groups (P = 0.565). The 1-year, 2
      year, 3-year and 4-year progression-free survival rates were 96.7%, 90.0%, 83.3%,
      70.0% for Yanshu group, and 90.0%, 86.7%, 76.7%, 66.7% for control group,
      respectively, with no significant difference (P = 0.554). However, the reaction
      of mucosa of oral cavity, myelosuppression and thrombocytopenia in the Yanshu
      group were significantly lower than that in the control group (P < 0.05). The
      quality of life of the patients in the Yanshu group was significantly higher than
      that in the control group (P < 0.05). CONCLUSIONS: Yanshu injection combined with
      radiochemotherapy in patients with stage III nasopharyngeal carcinoma show a good
      efficacy and can reduce the side effects of radiochemotherapy of nasopharygeal
      carcinoma, and improve the quality of life of the patients.

PMID- 21875476
TI  - [Application of traditional Chinese patent drugs in cancer treatment].

PMID- 21875475
TI  - [Short-term intermittent prophylactic administration of recombinant human
      thrombopoietin attenuates chemotherapy-induced thrombocytopenia in lung cancer
      patients].
AB  - OBJECTIVE: To evaluate the efficacy of short-term intermittent prophylactic use
      of a recombinant human thrombopoietin (rhTPO) in chemotherapy-induced severe
      thrombocytopenia in lung cancer patients. METHODS: 24 advanced non-small cell
      lung cancer (NSCLC) patients who experienced severe thrombocytopenia in the last
      chemotherapy cycle received prophylactic rhTPO treatment in the next chemotherapy
      cycle (prophylactic treated cycle, PTC). rhTPO was given subcutaneously 300 U*kg(
      1)*d(-1) on days 2, 4, 6, and 9 after the initiation of chemotherapy. Platelet
      count was monitored and compared with that in the previous treatment cycle
      (control cycle, CC). RESULTS: The lowest platelet count in the prophylactic rhTPO
      cycle was significantly higher than that in control cycle [(56 +/- 16) * 10(9)/L
      vs. (28 +/- 13) * 10(9)/L, P < 0.001]. The duration of thrombocytopenia was also
      shortened by the prophylactic rhTPO [(8 +/- 2) d vs. (12 +/- 3) d, P < 0.001].
      The area under curve (AUC) of platelet count (21 days) was significantly
      increased [(3517 +/- 685) * 10(9)/L vs. (2063 +/- 436) * 10(9)/L, P < 0.001]. The
      time to platelet nadir and peak was not affected. CONCLUSION: Prophylactic use of
      rhTPO can attenuate the severity and shorten the duration of chemotherapy-induced
      thrombocytopenia in lung cancer patients.

PMID- 21875477
TI  - [State of art of the radiofrequency ablation of colorectal liver metastases].

PMID- 21875478
TI  - [nm23-H1-siRNA enhances the chemosensitivity to liposome-encapsulated paclitaxel
      in lung adenocarcinoma cells in vitro].
AB  - OBJECTIVE: To study the chemosensitivity of lung adenocarcinoma cell line A549
      cells to liposome-encapsulated paclitaxel after treatment by nm23-H1-small
      interference RNA (nm23-H1-siRNA) in vitro. METHODS: The A549 cells were divided
      into two groups: non-transfected group and nm23-H1-siRNA-transfected group.
      Western blot analysis was used to detect the expression of nm23-H1. MTT and flow
      cytometry were used to determine the cell mortality rate, apoptosis rate and cell
      cycle after liposome-encapsulated paclitaxel treatment in both groups. RESULTS:
      The expression of nm23-H1 in A549 cells was significantly decreased after
      transfection with nm23-H1-siRNA. After treatment for 48 hours with liposome
      encapsulated paclitaxel, the cell mortality rate was increased with the
      increasing concentration of liposome-encapsulated paclitaxel in both groups, but
      increased higher in the nm23-H1-siRNA-transfected group. When the concentration
      of liposome-encapsulated paclitaxel was above 5 ug/ml, the cell mortality rate
      was significantly higher than that in the non-transfected group (P < 0.05). The
      proportion of apoptotic cells also increased in the nm23-H1-siRNA-transfected
      group, compared with that of the non-transfected group (t = 3.812, P < 0.05),
      while the proportion of cells at S and G(2)/M phase decreased after transfection
      with nm23-H1-siRNA (S phase:t = 8.356, P < 0.05; G(2)/M phase:t = 7.256, P <
      0.05). CONCLUSIONS: Nm23-H1 is related with the chemoresistance to liposome
      encapsulated paclitaxel in lung adenocarcinoma cell line A549 cells. Inhibition
      of the expression of nm23-H1 by nm23-H1-siRNA can improve the in vitro
      chemosensitivity of A549 cells to liposome-encapsulated paclitaxel.

PMID- 21875479
TI  - [Inhibition of PDK1 gene expression in esophageal cancer EC9706 cells by RNA
      interference and its effect on their malignant biological behavior].
AB  - OBJECTIVE: To explore the silencing effects of RNA interference on the expression
      of 3-phosphoinositide-dependent protein kinase 1 (PDK1) gene, and the effects on
      malignant phenotypes of esophageal carcinoma EC9706 cells. METHODS: PDK1 siRNAs
      was transfected into the EC9706 cells. The expression of PDK1 mRNA was detected
      by reverse transcriptase polymerase chain reaction (RT-PCR). At the same time,
      expressions of PDK1, Akt and phosphorylated Akt proteins were detected by Western
      blot. Methyl thiazolyl tetrazolium assay (MTT) was used to examine the cell
      proliferation after transfection. Flow cytometry was used to determine the
      percentage of apoptosis cells, and Transwell chambers were used to detect the
      invasion ability of the cells. Tumor formation in nude mice was used to assess
      the tumorigenic characteristics in vivo. RESULTS: Compared with the non
      transfected group, PDK1 siRNA effectively inhibited the expression of PDK1 mRNA
      in EC9706 cells, with an inhibition rate of (28.5 +/- 4.2)% at 24 h, (51.1 +/-
      5.7)% at 48 h and (60.6 +/- 4.1)% at 72 h after transfection. The expressions of
      PDK1 and phosphorylated Akt protein were also knocked down by PDK1 siRNA (P <
      0.05). PDK1 siRNA significantly inhibited the cell proliferation and invasion,
      promoted the cell apoptosis, and inhibited the EC9706 cells proliferation in vivo
      and the expression of PDK1 protein in the transplanted tumors (P < 0.05).
      CONCLUSION: PDK1 may play an important role in esophageal cancer cell
      proliferation, invasion and apoptosis, and may serve as an effective target for
      cancer gene therapy.

PMID- 21875481
TI  - [Expression of ERK1/2 MAPK signaling transduction pathway in esophageal cancers
      in Kazakh patients].
AB  - OBJECTIVE: To investigate the expression variation and significance of ERK1/2
      MAPK signaling transduction pathway in the pathogenesis of esophageal squamous
      cell carcinoma (ESCC) in Kazakh patients. METHODS: The expression level of p
      ERK1/2 after serum starvation and treatment with U0126 inhibitor was detected in
      esophageal cancer cell line EC9706 by Western blot assay. The mRNA level of total
      ERK1/2 (t-ERK1/2) and expression level of t-ERK1/2 and p-ERK1/2 proteins of 25
      pairs of ESCC and adjacent normal esophageal mucosal tissues of Kazakh patients
      were examined and identified by real-time quantitative PCR (qRT-PCR) and Western
      blotting, respectively. The expression of p-ERK1/2 protein was verified by
      immunohistochemistry in 126 paraffin-embeded specimens, including 19 normal
      esophageal mucosa, 55 esophageal carcinomas in situ and 52 invasive carcinomas.
      RESULTS: ERK1/2 MAPK signaling transduction pathway was in an active status in
      the EC9706 cells. The expression level of p-ERK1/2 in Ec9706 cells reached a peak
      at 10 min after transient serum stimulation, and p-ERK1/2 expression was totally
      restrained after the treatment with 50 umol/L U0126. In the 25 pairs of ESCC and
      adjacent normal mucosa, the t-ERK1 mRNA level was 1.92 +/- 3.49 in the ESCC
      tissues and 3.67 +/- 7.47 in the adjacent normal mucosa. The t-ERK1 mRNA level in
      ESCC tissues was significantly lower than that in adjacent normal mucosa (P <
      0.05), whereas there was no significant difference of t-ERK2 mRNA level between
      them(P > 0.05). The expression levels of p-ERK1 and p-ERK2 proteins were 0.87 +/-
      0.14 and 0.79 +/- 0.10 in the ESCC tissues, and 1.10 +/- 0.13 and 1.32 +/- 0.12
      in the adjacent normal mucosae. p-ERK1/2 protein in the ESCC tissues was
      significantly lower than that in the adjacent normal tissue (P < 0.01). However,
      there was no significant difference between their t-ERK1/2 protein levels (P >
      0.05). In the 126 cases of paraffin-embeded specimens, positive expressions of
      both p-ERK1 and p-ERK2 in esophageal cancer tissues were 7.7% (4/52),
      significantly lower than those in adjacent normal mucosa (31.6%, 6/19) and
      carcinoma in situ (85.5%, 47/55, P < 0.05). CONCLUSIONS: ERK1/2 MAPK signaling
      pathway is in an active status in esophageal cancer and adjacent normal mucosa.
      Our results imply that the activation of p-ERK1/2 MAPK signaling transduction
      pathway plays a role in the early pathogenesis of ESCC in Kazakh patients.

PMID- 21875480
TI  - [Comparison of the effect of rh-endostatin on intratumoral and myocardial
      micrangium in mice].
AB  - OBJECTIVE: To compare the effect of rh-endostatin on micrangium in tumor and
      myocardial tissue in nude mice. METHODS: Nude mice were randomized into 4 groups
      (10 mice in each group), blank control group (without tumor burden, received NS
      100 ul*d(-1) injection), drug control group (without tumor burden, received rh
      endostatin 400 ug*d(-1) injection), model group (with tumor burden, received NS
      100 ul*d(-1) injection) and treatment group (with tumor burden, received rh
      endostatin 400 ug*d(-1) injection) for 28 days. The tumor volume and body weight
      of the mice were measured before and after administration. The expression of
      CD34, MMP-2, MMP-9, HIF-1alpha and VEGF in the myocardium and tumor were detected
      by immunohistochemistry. The vascular structure was observed by immunoenzymatic
      CD34 and Masson double staining. RESULTS: The increase of tumor volume of the
      treatment group [(48.18 +/- 37.31) mm(3)] was significantly lower than that in
      the model group [(113.80 +/- 73.27) mm(3)). The changes of body weight was not
      significant different among the four groups. After treated with rh-endostatin,
      the expressions of MMP-9 and VEGF in tumors were significantly down-regulated,
      but the expressions of MMP-2 and HIF-1alpha in the tumor were not. The
      microvessel density (MVD) in the tumors of treatment group was significantly
      decreased compared with that of model group. The proportion of tumor vessels
      covered by collagen in the treatment group was increased compared with that of
      the model group. However, MVD and micrangium in myocardium were not changed
      significantly. CONCLUSION: Rh-endostatin can decrease the expression of MMP-9,
      VEGF and MVD, inhibit the tumor growth and normalize tumor micrangium in tumor
      but not weaken the MMPs and MVD of mature micrangium in myocadium.

PMID- 21875482
TI  - [Correlation between expression of forkhead box M1 (FOXM1) and
      clinicopathological features and prognosis in patients with non-small cell lung
      cancer (NSCLC)].
AB  - OBJECTIVE: To investigate the expression of forkhead box M1 (FOXM1) and its
      correlation with clinicopathological features and prognosis in patients with non
      small cell lung cancer (NSCLC). METHODS: The expression of FOXM1 in 68 cases of
      NSCLC was detected by immunohistochemistry. The FOXM1 expression in 6 tumor
      tissues (3 cases with negative and 3 cases with positive expression of FOXM1) was
      analyzed by Western blotting to confirm the immunohistochemical results. The
      correlation of the expression of FOXM1 with clinicopathalogical features and
      overall survival of the NSCLC patients was analyzed. RESULTS: The expression of
      FOXM1 protein was detected in the nuclei or cytoplasms of the tumor cells. The
      positive expression rate of FOXM1 was 36.8% (25/68). Western blotting confirmed
      the immunohistochemical results. The expression level of FOXM1 in advanced stage
      cancer was significantly higher than that in early stage NSCLC (P = 0.001). The
      median OS was 23.0 months in patients with negative expression of FOXM1 and 13.0
      months in those with positive expression (P = 0.001). Univariate analysis
      revealed that histological grade, lymph nodes status, TNM stage and FOXM1
      expression were significantly associated with prognosis in the NSCLC patients (P
      < 0.05). The Cox multivariate analysis demonstrated that lymph nodes status, TNM
      stage and FOXM1 expression were independent poor prognostic factors (P < 0.05).
      CONCLUSION: The expression status of FOXM1 in NSCLC is an independent prognostic
      factor and negatively correlated with prognosis.

PMID- 21875483
TI  - [Association of serum EGFR protein concentration with the efficacy of Gefitinib
      in the treatment of advanced non-small cell lung cancer].
AB  - OBJECTIVE: To analyze the association between the EGFR protein level and the EGFR
      gene mutation status in advanced non-small cell lung cancer (NSCLC), and to
      explore whether the EGFR protein level is related to the efficacy and survival of
      the EGFR-TKI drug Gifitinib-treated patients with advanced NSCLC. METHODS: Ninety
      nine cases were enrolled in this study. Pathological tissue specimens and paired
      peripheral blood samples were collected. Exons 19 and 21 of the EGFR gene
      mutation were detected by direct sequencing. The concentration of plasma EGFR
      protein was detected by ELISA. Univariate and multivariate statistical analyses
      of the efficacy and survival were performed using SPSS 13.0 software. RESULTS:
      The response rate (RR) and clinical benefit rate (CBR) of Gefitinib-treated
      patients were 51.5% and 79.8%, respectively. There were 35 (35.4%) with positive
      EGFR gene mutation of the 99 samples. The concentration limit of EGFR protein was
      55.42 ug/L. The RR and CBR of patients with EGFR gene mutation was significantly
      higher than those without mutation (65.7% vs. 43.8%, P = 0.037; 94.3% vs. 71.9%,
      P = 0.008). The median PFS was prolonged (23 months vs. 10 months, P = 0.014).
      The CBR of patients with high EGFR protein expression (concentration >= 55.42
      ug/L) was significantly higher than those with low expression (90.0% vs 64.1%, P
      = 0.004), and the median PFS was prolonged (21 months vs. 8 months, P = 0.016).
      EGFR protein level was an independent factor affecting the EGFR gene mutation
      status. The Correlation between EGFR gene mutation status and EGFR protein level
      was positive. CONCLUSIONS: Gefitinib is effective in the treatment of advanced
      NSCLC patients with EGFR gene mutation and high EGFR protein expression. EGFR
      protein level in peripheral blood may be a molecular biomarker in prediction of
      efficacy and survival of the Gefitinib treatment in patients with advanced NSCLC.

PMID- 21875484
TI  - [Value of serum carcinoembryonic antigen in prediction of chemotherapy efficacy
      and prognosis in patients with advanced non-small cell lung cancer treated with
      EGFR-tyrosine kinase inhibitor].
AB  - OBJECTIVE: The aim of this study was to detect the pre- and post-treatment serum
      carcinoembryonic antigen (CEA) levels after 4 weeks of EGFR-TKIs treatment in
      advanced non-small cell lung cancer (NSCLC) patients to evaluate the clinical
      value of CEA in the prediction of chemotherapy response and prognosis in those
      patients. METHODS: Pre- and post-treatment serum CEA levels of the patients were
      measured with immunoradiometric kits after 4 weeks of EGFR-TKIs treatment to
      evaluate the relationship between chemotherapy response and prognosis. RESULTS:
      After 4 weeks of EGFR-TKIs treatment, one patient in the total of 75 patients
      (1.3%) achieved complete response (CR), 17 patients (22.7%) achieved partial
      response (PR), 31 patients (41.3%) achieved disease stable (SD) and 26 patients
      had progressive disease (PD). The radiological objective response rate(ORR) and
      disease control rate (DCR) were 24.0% and 65.3%, respectively. The median
      survival time (MST) of all patients was 8.1 months. The MST of SD patients was
      similar to that in the OR patients (P = 0.06), but both longer than that in the
      PD patients (P < 0.001). The MST of DC patients was similar to that in OR
      patients (P = 0.358), but longer than that in PD patients (P < 0.001). Serum CEA
      levels decreased >= 32% and >= 61% were closely related with the objective
      response and disease control. The median survival time (MST) of patients with
      serum CEA decreased >= 32% was longer than those with CEA decreased < 32% (9.5
      months vs 6.7 months, P < 0.0001). The MST of patients with serum CEA decreased
      >= 32% was similar to those with CEA decreased >= 61% (9.5 months vs 10.5 months,
      P = 0.370), but both longer than those with CEA decreased < 32% (6.7 months, P <
      0.001). Cox multivariate survival analysis confirmed that serum CEA level
      decreased >= 32%, CEA level decreased >= 61%, PS score, and DC are independent
      prognostic factor, but not OR. CONCLUSIONS: To advanced NSCLC patients, the
      disease control rate (DCR) may be more suitable than objective response rate
      (ORR) as an indicator in predicting the efficacy and prognosis in advanced NSCLC
      patients. Serum CEA levels decreased >= 32% may be a reliable indicator to
      determine the therapeutic efficacy of EGFR-TKIs.

PMID- 21875485
TI  - [Clinical significance of C-reactive protein in patients with stage I non-small
      cell lung cancer].
AB  - OBJECTIVE: The aim of this study was to investigate the association between
      preoperative C-reactive protein (CRP) level and pathologic features in patients
      with stage I non-small cell lung cancer (NSCLC), and also to analyze if CRP
      provides prognostic information for NSCLC patients. METHODS: The
      clinicopathological data of 105 patients with stage I NSCLC, who underwent
      pulmonary resection in Shanghai Chest hospital from Mar 1999 to Jul 2004, were
      retrospectively reviewed. The association between preoperative CRP levels and
      several clinical variables was analyzed by chi square test. Logistic regression
      analysis was used for multivariate analysis. Kaplan-Meier method and Cox
      multivariate regression model was used to examine the prognostic significance of
      the covariates on survival. RESULTS: Among the 105 cases, 69 had CRP at normal
      level (<= 5 mg/L) and 36 at increased level (> 5 mg/L). The patients who were
      male (P < 0.001), smoking (P = 0.002), with squamous cell carcinoma (P < 0.001),
      poor differentiation (P < 0.001), tumor size larger than 3 cm (P < 0.001) had a
      higher serum CRP level. The maxmal tumor diameter (P = 0.037) was an independent
      risk factor for preoperative serum CRP level elevation. The five-year survival
      rate and five-year disease free survival rate of the higher CRP group were lower
      than that in the normal CRP group (55.6% vs. 79.7%, P < 0.05, and 41.7%vs. 68.1%,
      P < 0.05, respectively). Cox regression analysis demonstrated that the CRP level
      had effect on overall survival (P = 0.009) and disease free survival (P = 0.019).
      CONCLUSIONS: Our findings indicate that the maximal tumor diameter is an
      independent risk factor for preoperative serum CRP level elevation. The overall
      survival, disease free survival, five-year survival rate and five-year disease
      free survival rate of the higher CRP group are lower than that in the normal CRP
      group.

PMID- 21875486
TI  - [Robo1 expression in breast cancer and its relationship to brain metastasis].
AB  - OBJECTIVE: To detect the expression of Robo1 in different breast tumors and its
      association with the breast cancer brain metastasis. METHODS: Labelled
      streptavidin-biotin (LSAB) staining was used to examine the Robo1 expression in
      specimens from 24 cases of invasive ductal carcinoma (IDC) with brain metastasis,
      71 cases of IDC without brain metastasis, 22 cases of ductal carcinoma in situ
      (DCIS) and 23 cases of fibroadenoma. RESULTS: The expression pattern of Robo1 in
      DCIS (59.1%) and IDC (45.3%) was significantly lower than that in adenofibroma
      (87.0%, P < 0.05). The expression of Robo1 in IDC with brain metastasis (12.5%)
      was significantly lower than that in IDC without brain metastasis (56.3%, P <
      0.05). The expression of Robo1 was much higher in more than 50 year-old-group
      (57.8%) than that in less than 50 year-old-group (34.0%) of IDC patients. The
      overall survival time in patients with the Robo1 negative expression was
      significantly shorter than those with positive expression (P < 0.05). No
      correlation was found between the Robo1 expression and the tumor size, lymph node
      metastasis, pathologic stage, histological grade and clinical stage (P > 0.05).
      CONCLUSIONS: The Robo1 expression correlates negatively with IDC brain
      metastasis, and correlates positively with the age and prognosis of IDC patients.
      Robo1 may be applied as a marker in evaluation of the IDC prognosis and brain
      metastasis.

PMID- 21875487
TI  - [Abnormal expression of RSK-4 and its clinical significance in breast cancer].
AB  - OBJECTIVE: To study the expression and clinical significance of ribosomal S6
      kinase-4 (RSK-4) in breast cancer and explore the role of RSK-4 in the genesis
      and development of breast cancer. METHOD: The expression levels of RSK-4 mRNA and
      protein were detected in 56 cases of breast cancer and the normal breast tissues,
      as well as in 20 cases of breast benign lesions, by reverse transcriptase
      polymerase chain reaction (RT-PCR) and immunohistochemistry. RESULTS: The
      expression rates of RSK-4 mRNA in breast cancer, the normal breast tissues and
      breast benign lesions were 48.2%, 76.8% and 75.0%, respectively. The expression
      level of RSK-4 mRNA in breast cancer was significantly lower than those in normal
      breast tissues and breast benign lesions tissues (P < 0.05). The expression level
      of RSK-4 significantly correlated with tumor size and clinical stage (P <
      0.05).The expression rate of RSK-4 protein was 39.3% in breast cancer tissues,
      which was significantly lower than that of normal breast tissues (71.4%) and
      breast benign lesions (75.0%, P < 0.01). The expression level of RSK-4 protein
      was lower in breast cancer with large tumor, high clinical stage and lymph node
      metastasis. In 56 cases of breast cancer samples, the consistency rate of RSK-4
      mRNA and protein was 73.2%. A significant correlation was found between RSK-4
      mRNA and protein (chi2 = 10.254, P < 0.05). CONCLUSION: The down-regulation of
      RSK-4 expression in breast caner suggests that it is a breast cancer suppressor
      gene, and the lack or down-regulation of RSK-4 expression is involved in the
      genesis and progression of breast cancer.

PMID- 21875489
TI  - [Association between lymphangiogenesis and clinicopathological features and
      prognosis in laryngeal carcinoma].
AB  - OBJECTIVE: To detect lymphangiogenesis by labeling the lymphatic endothelial
      marker, lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1), and study
      the prognostic relevance of lymphangiogenesis in laryngeal squamous carcinoma.
      METHODS: Clinical files and specimens of 78 patients with histologically
      diagnosed laryngeal carcinoma were stained with LYVE-1 as a specific lymphatic
      endothelial marker. The lymphatic vessel density (LVD) was measured, and the
      correlation between LVD and clinicopathological features of the tumor cases was
      analyzed. RESULTS: The mean LVD in laryngeal carcinoma (13.24 +/- 5.09) was
      significantly higher than that in adult laryngeal papilloma (5.54 +/- 3.15) and
      squamous dysplasia (6.76 +/- 4.45, P < 0.05). The LVD of poorly differentiated
      tumors (15.74 +/- 5.24) was significantly higher than that in the moderately
      differentiated tumors (13.84 +/- 6.20), and the LVD in the moderately
      differentiated tumors was significantly higher than that in the well
      differentiated tumors (11.68 +/- 6.34). The LVD in stage 0 to stage II group
      (10.66 +/- 5.70) was significantly lower than that in the stage III to IV group
      (17.01 +/- 6.35). The lymph node metastasis group (17.25 +/- 7.37) was
      significantly higher than non-lymph node metastasis group (8.60 +/- 5.23, P <
      0.05). There was no significant association between LVD and age, sex, primary
      site and distant metastasis. The overall survival in the patients with a LVD
      higher than the mean value was 33.5 month, and that of cases with a LVD lower
      than the mean value was 81.6 month (P < 0.05). The multivariate survival analysis
      showed that the clinical stage and LVD were independent prognostic factors of
      laryngeal cancer. CONCLUSIONS: The LYVE-1 staining histochemistry demonstrates
      that the lymphangiogenesis occurrs mainly at the edge of the tumors, and
      lymphangiogenesis plays an important role in the carcinogenesis, cancer
      progression and lymph node metastasis in laryngeal cancer. LVD may be an
      independent indicator of poor prognosis of laryngeal cancer.

PMID- 21875488
TI  - [Relationship between BRCA1 mRNA expression in tumor cells from malignant
      effusions and chemosensitivity to cisplatin in patients with metastatic malignant
      effusions].
AB  - OBJECTIVE: To explore the mRNA expression of breast cancer susceptibility gene 1
      (BRCA1) in tumor cells isolated from malignant pleural and peritoneal effusions,
      and the predictive role of BRCA1 related to the efficacy of cisplatin-based
      chemotherapy. METHODS: Tumor cells were isolated from malignant pleural and
      peritoneal effusions of 31 cancer patients. The response of these tumor cells to
      cisplatin was determined by CCK8 assay. Real time quantitative RT-PCR was used to
      examine the BRCA1 mRNA level in the primary culture cancer cells. RESULTS: The
      expression level of BRCA1 mRNA was 0.618 (0.014 - 18.063) in primary culture
      tumor cells. The IC(50) of DDP was 2.809 ug/ml in the primary culture tumor cells
      (0.118 - 19.439 ug/ml). Both BRCA1 mRNA expression and the tumor cells IC(50) of
      DDP were not significantly related with patient age, gender, the type of primary
      tumor, whether to accept the chemotherapy and effusion type (P > 0.05). The level
      of BRCA1 mRNA was negatively correlated with the chemosensitivity in terms of
      IC(50) of cisplatin (P < 0.001). CONCLUSION: Assessment of expression level of
      BRCA1 mRNA may be useful in predicting the efficacy of cisplatin-based
      chemotherapy in patients with metastatic malignant effusions.

PMID- 21875490
TI  - [Value of BI-RADS ultrasonic scores of direct and indirect ultrasonographic signs
      in diagnosis of solid breast lesions].
AB  - OBJECTIVE: To explore the value of BI-RADS ultrasonic scores of direct and
      indirect ultrasonographic signs in diagnosis of solid breast lesions. METHODS:
      Reference to the standard BI-RADS score, ultrasonic scores of direct and indirect
      ultrasonographic signs of 132 solid breast lesions were assigned, and were
      compared with pathological results. RESULTS: By the direct signs of breast
      lesions (aspect ratio, shape, border, internal echo, posterior echo, flow grade,
      sand-like calcification) and indirect signs (changes in local skin thickness,
      Cooper ligament changes, axillary lymph nodes, depth of reinforcement membrane
      changes, mass changes in the surrounding burr), the integral from the total
      scores in benign and malignant breast masses showed a statistically significant
      difference. The total score of malignant lesions (8.94 +/- 2.85) was
      significantly higher than that of benign tumors (3.09 +/- 1.97, P < 0.05). Except
      skin thickness, all the remaining scores of the signs of benign and malignant
      breast tumors showed a significant difference between the two groups (P < 0.05).
      By receiver operating curve (ROC) analysis, the best critical value of the total
      score of direct signs was >= 4, with a sensitivity and specificity of 0.84 and
      0.93, respectively, in distinguishing breast carcinoma from benign lesions. The
      best critical value of the total score of indirect signs was >= 1, with a
      sensitivity and specificity of 0.82 and 0.74, respectively. The critical value of
      the combination of the direct and indirect signs was >= 5 in differential
      diagnosis of malignant and benign lesions, with a sensitivity and specificity
      value of 0.88 and 0.90, respectively. CONCLUSION: The assignment score to the
      ultrasound characteristics of the direct and indirect signs of solid breast
      lesions can make a more objective diagnosis, yet it is a simple, effective,
      comprehensive and semi-quantitative analysis method.

PMID- 21875491
TI  - [Advanced dermatofibrosarcoma protuberans treated with imatinib mesylate].
AB  - OBJECTIVE: To evaluate the efficacy, side effects and toxicity of imatinib
      mesylate in the treatment of patients with locally advanced and/or metastatic
      dermatofibrosarcoma protuberans (DFSP). METHODS: Twenty-four cases of advanced
      DFSP diagnosed by pathology and treated in our hospital from Nov. 2004 to Oct.
      2009 were included in this study. The patients were treated with imatinib
      mesylate (dosage: 400 mg, po, qd) and carefully observed for treatment efficacy,
      side effects and survival time. There were 2 patients taking the drug as second
      line therapy, and other 22 patients as third or more than third line therapy.
      RESULTS: The 24 patients were evaluable for the efficacy. There were 8 patients
      (33.3%) with CR, 10 pts (41.7%) PR, 2 patients (8.3%) SD, and 4 patients (16.7%)
      PD. The disease control rate (DCR = CR+PR+SD) was 83.3%. The median response time
      in 18 cases with CR and PR was 5.6 months. The median survival time in 20 cases
      with disease control was 30 months, however, that in nonresponse (PD) cases was
      only 10 months. Side reactions related to imatinib mesylate included nausea and
      vomiting (20.8%), neutropenia (12.5%), and edema (8.3%). CONCLUSIONS: Our results
      are consistent with previous reports in the literature. Imatinib is a safe and
      effective moleucular target drug used for Chinese. Only mild adverse reactions
      occur in the treated patients. It is worth using imatinib in the treatment of
      advanced DFSP patients.

PMID- 21875492
TI  - [Diagnostic value of CT-guided extrapleural locating transthoracic automated
      cutting needle biopsy of lung lesions].

PMID- 21875493
TI  - [Analysis of diagnosis and treatment for 45 patients with gallbladder cancer].

PMID- 21875494
TI  - Administration route and carrier dependent effects on vaccine efficacy:
      implications for vaccine design.

PMID- 21875495
TI  - Intra-acinar trypsinogen activation mediates early stages of pancreatic injury
      but not inflammation in mice with acute pancreatitis.
AB  - BACKGROUND & AIMS: The role of trypsinogen activation in the pathogenesis of
      acute pancreatitis (AP) has not been clearly established. METHODS: We generated
      and characterized mice lacking trypsinogen isoform 7 (T7) gene (T(-/-)). The
      effects of pathologic activation of trypsinogen were studied in these mice during
      induction of AP with cerulein. Acinar cell death, tissue damage, early intra
      acinar activation of the transcription factor nuclear factor kappaB (NF-kappaB),
      and local and systemic inflammation were compared between T(-/-) and wild-type
      mice with AP. RESULTS: Deletion of T7 reduced the total trypsinogen content by
      60% but did not affect physiologic function. T(-/-) mice lacked pathologic
      activation of trypsinogen, which occurs within acinar cells during early stages
      of AP progression. Absence of trypsinogen activation in T(-/-) mice led to near
      complete inhibition of acinar cell death in vitro and a 50% reduction in acinar
      necrosis during AP progression. However, T(-/-) mice had similar degrees of local
      and systemic inflammation during AP progression and comparable levels of intra
      acinar NF-kappaB activation, which was previously shown to occur concurrently
      with trypsinogen activation during early stages of pancreatitis. CONCLUSIONS: T7
      is activated during pathogenesis of AP in mice. Intra-acinar trypsinogen
      activation leads to acinar death during early stages of pancreatitis, which
      accounts for 50% of the pancreatic damage in AP. However, progression of local
      and systemic inflammation in AP does not require trypsinogen activation. NF
      kappaB is activated early in acinar cells, independently of trypsinogen
      activation, and might be responsible for progression of AP.

PMID- 21875496
TI  - Luminal CD4+ T cells penetrate gut epithelial monolayers and egress from lamina
      propria to blood circulation.
AB  - BACKGROUND & AIMS: The egress of memory T cells from peripheral tissues, such as
      lung and skin, into the draining lymph nodes requires their expression of CC
      chemokine receptor 7 (CCR7). In the intestine, resident memory T cells in the
      intestinal lamina propria (LP) do not express CCR7, indicating that they are
      tissue bound and do not exit the intestine. METHODS: We developed a cell transfer
      system, using rectal administration of lymphocytes to C57BL/6 mice. Lymphotoxin
      alpha-deficient mice were crossed with RAG-2(-/-) (recombination-activating gene
      2) mice to generate lymphotoxin alpha-deficient * RAG-2(-/-) mice. RESULTS:
      Severe combined immunodeficient (SCID) or RAG-2(-/-) mice given rectal
      administration of splenic CD4(+) T cells from normal mice developed colitis; the
      cells proliferated not only in the LP but also in spleen. SCID or RAG-2(-/-) mice
      given rectal administrations of CD4(+) T cells that expressed green fluorescent
      protein (GFP(+)CD4(+) T cells) localized to the LP within 6 hours but were not
      found in the spleen until 24 hours after administration. Immunohistochemical and
      electron microscopic analyses detected CD4(+) T cells in the intraepithelial
      space just 3 hours after intrarectal administration. However, neither CCR7
      deficiency nor the sphingosine-1-phosphate receptor agonist Fingolimod impaired
      the egress of CD4(+) T cells from LP to systemic circulation. CONCLUSIONS: CD4(+)
      T cells not only penetrate from the luminal side of the intestine to the LP but
      also actively egress from the LP into the circulation. We developed a rectal
      administration system that might be used to further investigate cell trafficking
      in intestinal mucosa and to develop enema-based therapeutics for intestinal
      diseases.

PMID- 21875497
TI  - Activity of protease-activated receptors in the human submucous plexus.
AB  - BACKGROUND & AIMS: Protease-activated receptors (PARs) are expressed in the
      enteric nervous system. Excessive release of proteases has been reported in
      functional and inflammatory bowel diseases. Studies in several animal models
      indicate the involvement of neural PARs. We studied the actions of different PAR
      activating peptides (AP) in the human submucous plexus and performed comparative
      studies in guinea pig submucous neurons. METHODS: We used voltage- and calcium
      sensitive dye recordings to study the effects of PAR1-AP, PAR2-AP, PAR4-AP, the
      PAR1 activator thrombin, and the PAR2 activator tryptase on neurons and glia in
      human and guinea pig submucous plexus. Human preparations were derived from
      surgical resections. Levels of mucosal secretion evoked by PAR-APs were measured
      in Ussing chambers. RESULTS: PAR1-AP and thrombin evoked a prominent spike
      discharge and intracellular Ca(2+) concentration ([Ca](i)) transients in most
      human submucous neurons and glia. PAR2-AP, tryptase, and PAR4-AP caused
      significantly weaker responses in a minor population. In contrast, PAR2-AP evoked
      much stronger responses in enteric neurons and glia of guinea pigs than did PAR1
      AP or PAR4-AP. PAR1-AP, but not PAR2-AP or PAR4-AP, evoked a nerve-mediated
      secretion in human epithelium. The PAR1 antagonist SCH79797 inhibited the PAR1
      AP, and thrombin evoked responses on neurons, glia, and epithelial secretion. In
      the submucous layer of human intestine, but not guinea pig intestine, PAR2-AP
      evoked [Ca](i) signals in CD68(+) macrophages. CONCLUSIONS: In the human
      submucous plexus, PAR1, rather than PAR2 or PAR4, activates nerves and glia.
      These findings indicate that PAR1 should be the focus of future studies on neural
      PAR-mediated actions in the human intestine; PAR1 might be developed as a
      therapeutic target for gastrointestinal disorders associated with increased
      levels of proteases.

PMID- 21875498
TI  - Antibodies against tumor necrosis factor (TNF) induce T-cell apoptosis in
      patients with inflammatory bowel diseases via TNF receptor 2 and intestinal CD14+
      macrophages.
AB  - BACKGROUND & AIMS: The anti-tumor necrosis factor (TNF) antibodies infliximab,
      adalimumab, and certolizumab pegol have proven clinical efficacy in Crohn's
      disease. Here, we assessed the effects of anti-TNF antibodies on apoptosis in
      inflammatory bowel disease (IBD). METHODS: CD14(+) macrophages and CD4(+) T cells
      were isolated from peripheral blood and lamina propria mononuclear cells from
      patients with IBD and control patients. Cell surface markers and apoptosis were
      assessed by immunohistology and fluorescence-activated cell sorting techniques.
      RESULTS: Lamina propria CD14(+) macrophages showed significantly more frequent
      and higher membrane-bound TNF (mTNF) expression than CD4(+) T cells in IBD,
      whereas mTNF-dependent signaling proteins such as TNF receptor (TNFR) 2, TNFR
      associated factor (TRAF) 2, and nuclear factor kappaB were induced in IBD mucosal
      CD4(+) T cells. Most anti-TNF antibodies did not induce T-cell apoptosis in
      purified peripheral or mucosal CD4(+) T cells. However, in contrast to
      etanercept, administration of all clinically effective anti-TNF antibodies
      resulted in a significant induction of T-cell apoptosis in IBD when lamina
      propria CD4(+) T cells expressing TNFR2(+) were cocultured with mTNF(+) CD14(+)
      intestinal macrophages. In contrast, no effects in control patients were noted. T
      cell apoptosis in IBD occurred in vivo after treatment with adalimumab and
      infliximab, was critically dependent on TNFR2 signaling, and could be prevented
      via interleukin-6 signal transduction. Blockade of interleukin-6R signaling
      augmented anti-TNF-induced T-cell apoptosis in IBD. CONCLUSIONS: Clinically
      effective anti-TNF antibodies are able to induce T-cell apoptosis in IBD only
      when mucosal TNFR2(+) T cells are cocultured with mTNF-expressing CD14(+)
      macrophages. The finding that anti-TNF antibodies induce apoptosis indirectly by
      targeting the mTNF/TNFR2 pathway may have important implications for the
      development of new therapeutic strategies in IBD.

PMID- 21875499
TI  - Touching some firm ground in the epidemiology of NASH.

PMID- 21875500
TI  - Cardioprotective effect of therapeutic hypothermia at 34 degrees C against
      ischaemia/reperfusion injury mediated by PI3K and nitric oxide in a rat isolated
      heart model.
AB  - AIM: Therapeutic hypothermia (TH) is widely used as a cardioprotective treatment
      for cardiac arrest. TH at 30-32 degrees C during ischaemia and reperfusion has a
      cardioprotective effect. The aims of the study were to examine whether TH at 34
      degrees C with late induction (immediately after the start of reperfusion) has a
      cardioprotective effect and to determine if this effect is mediated by nitric
      oxide (NO) and phosphatidylinositol 3'-kinase (PI3K). METHODS: Langendorff
      perfusion of Sprague-Dawley rat hearts was initiated at 75 mmHg at 37 degrees C.
      Left ventricle infarct sizes were evaluated by triphenyltetrazolium chloride
      staining after Langendorff perfusion in 6 groups (each n=7): control group;
      ischaemia group, with 34 degrees C TH during ischaemia for 30 min and reperfusion
      for 180 min; reperfusion group, with 34 degrees C TH induced solely during the
      reperfusion period; the l-NAME (NO synthase inhibitor), LY294002, and wortmannin
      (PI3K inhibitors) groups, which were treated similarly to the reperfusion group
      with the addition of each compound. RESULTS: TH reduced the left ventricle
      infarct size from 54.2 +/- 14.8% of the control group to 11.9 +/- 6.3% (ischaemia
      group, p<0.001) and to 23.5 +/- 10.5% (reperfusion group, p<0.001). l-NAME,
      LY294002, and wortmannin reversed the cardioprotective effect of TH induced
      during reperfusion to 42.5 +/- 10.6% (p=0.009), 40.9 +/- 4.1% (p=0.021), and
      51.9+/-13.0% (p<0.001), respectively. Circulatory temperatures reached 34 degrees
      C within 5 min in all groups subjected to TH. CONCLUSIONS: TH of 34 degrees C
      showed a cardioprotective effect even with late initiation of cooling during
      reperfusion. The effect was mediated by NO and PI3K.

PMID- 21875501
TI  - A new external cardiopulmonary resuscitation device: what are the requirements
      for its use in a pre-hospital setting?

PMID- 21875502
TI  - Cardiopulmonary resuscitation monitoring for EMT volunteers: a two year
      evaluation of practice.

PMID- 21875504
TI  - Association between calcineurin inhibitor blood concentrations and outcomes after
      allogeneic hematopoietic cell transplantation.
AB  - To determine whether calcineurin inhibitor (CNI) blood concentrations within the
      first month after allogeneic hematopoietic cell transplantation (HCT) correlated
      with the incidence of graft-versus-host disease (GVHD) and other outcomes, we
      retrospectively analyzed data from 1181 patients with hematologic malignancies
      who had HCT from HLA-matched related (n = 634) or unrelated (n = 547) donors at a
      single institution between 2001 and 2009. After myeloablative HCT (n = 774),
      higher CNI concentrations were not associated with lower risks of acute or
      chronic GVHD (aGVHD, cGVHD). After nonmyeloablative HCT (n = 407), higher
      cyclosporine concentrations were associated with decreased risks of grade 2-4 and
      3-4 aGVHD (hazard ratio [HR] per 100 ng/mL change in cyclosporine concentrations,
      0.7; 95% confidence interval [CI], 0.6-0.82; and HR, 0.66, 95% CI, 0.49-0.9,
      respectively), nonrelapse mortality (HR, 0.6, 95% CI, 0.41-0.88), and overall
      mortality (HR, 0.83, 95% CI, 0.71-0.99). Cyclosporine concentrations were not
      associated with risks of cGVHD and recurrent malignancy after nonmyeloablative
      HCT. Among patients given tacrolimus after nonmyeloablative HCT, a similar trend
      of CNI-associated GVHD-protection was observed. Higher CNI concentrations were
      not associated with apparent renal toxicity. We conclude that higher cyclosporine
      concentrations relatively early after nonmyeloablative HCT confer protection
      against aGVHD that translates into reduced risks of nonrelapse and overall
      mortality.

PMID- 21875503
TI  - Immune reconstitution after double umbilical cord blood stem cell
      transplantation: comparison with unrelated peripheral blood stem cell
      transplantation.
AB  - Double umbilical cord blood (DUCB) transplantation is an accepted transplantation
      strategy for patients without suitable human leukocyte antigen (HLA) matched
      donors. However, DUCB transplantation is associated with increased morbidity and
      mortality because of slow recovery of immunity and a high risk of infection. To
      define the differences in immune reconstitution between DUCB transplantation and
      HLA matched unrelated donor (MUD) transplantation, we performed a detailed,
      prospective analysis of immune reconstitution in 42 DUCB recipients and 102
      filgrastim-mobilized unrelated peripheral blood stem cell recipients.
      Reconstitution of CD3 T cells was significantly delayed in the DUCB cohort
      compared with the MUD cohort for 1 to 6 months posttransplantation (P < .001),
      including naive (CD45RO-) and memory (CD45RO+) CD4 T cells, regulatory (CD4CD25)
      T cells, and CD8 T cells. In contrast, CD19 B cells recovered more rapidly in the
      DUCB cohort and numbers remained significantly greater from 3 to 24 months after
      transplantation (P = .001). CD56CD16 natural killer (NK) cells also recovered
      more rapidly in DUCB recipients and remained significantly greater from 1 to 24
      months after transplantation. B cell activating factor (BAFF) levels were higher
      in the DUCB cohort at 1 month (P < .001), were similar in both cohorts at 3 and 6
      months, and were lower in the DUCB cohort at 12 months (P = .002). BAFF/CD19 B
      cell ratios were lower in the DUCB cohort at 3 (P = .045), 6 (P = .02), and 12
      months (P = .002) after transplantation. DUCB recipients had more infections
      within the first 100 days after transplantation (P < .001), and there was less
      chronic graft-versus-host disease (P < .001), but there were no differences in
      cumulative incidence of relapse, nonrelapse death, progression-free survival, or
      overall survival between the 2 groups. These results suggest that increased risk
      of infections is specifically associated with delayed reconstitution of all major
      T cell subsets, but the increased risk is limited to the first 3 months after
      DUCB transplantation. There is no increased risk of relapse, suggesting that
      graft-versus-leukemia activity is maintained. Early reconstitution of B cells and
      NK cells may, in part, account for these findings.

PMID- 21875506
TI  - Advanced heart failure.

PMID- 21875505
TI  - Characteristics of CliniMACS(r) System CD34-enriched T cell-depleted grafts in a
      multicenter trial for acute myeloid leukemia-Blood and Marrow Transplant Clinical
      Trials Network (BMT CTN) protocol 0303.
AB  - Eight centers participated in the Blood and Marrow Transplant Clinical Trials
      Network (BMT CTN) protocol 0303 to determine the effect of extensive T cell
      depletion (TCD) on the outcome of HLA matched sibling donor transplantation for
      acute myeloid leukemia. One goal of the study was to determine if TCD could be
      performed uniformly among study sites. TCD was achieved using the CliniMACS((r))
      CD34 Reagent System for CD34 enrichment. Processed grafts needed to contain >=
      2.0 * 10(6) CD34(+)cells/kg with a target of 5.0 * 10(6) CD34(+) cells/kg and
      <10(5) CD3(+) T cells/kg. Up to 3 collections were allowed to achieve the minimum
      CD34(+) cell dose. In total, 86 products were processed for 44 patients.
      Differences in the starting cell products between centers were seen in regard to
      total nucleated cells, CD34(+) cells, and CD3(+) T cells, which could in part be
      ascribed to a higher dose of granulocyte-colony stimulating factor used for
      mobilization early in the trial. Differences between centers in processing
      outcomes were minimal and could be ascribed to starting cell parameters or to
      differences in graft analysis methods. Multivariate analysis showed that CD34(+)
      cell recovery (66.1% +/- 20.3%) was inversely associated with the starting number
      of CD34(+) cells (P = .02). Median purity of the CD34 enriched fraction was 96.7%
      (61.5%-99.8%) with monocytes and B cells the most common impurity. All patients
      received the minimum CD34(+) cell dose, and 39 patients (89%) came within 10% or
      exceeded the target CD34(+) cell dose without exceeding the maximum T cell dose.
      All patients proceeded to transplantation and all achieved initial engraftment.
      Products processed at multiple centers using the CliniMACS System for CD34
      enrichment were comparably and uniformly highly enriched for CD34(+) cells, with
      good CD34(+) cell recovery and very low CD3(+) T cell content.

PMID- 21875507
TI  - Epidemiology and cost of advanced heart failure.
AB  - The public health impact and the need to intervene upon the worsening heart
      failure (HF) epidemic are currently a matter of national interest. The greater
      than $39 billion annual cost of caring for the 5.8 million patients living with
      HF in the United States places a considerable burden on the health care system.
      In 2006, HF was a contributing factor in more than 250,000 deaths. HF is the
      primary cause of more than 1 million and a contributing cause for more than 3
      million hospitalizations. Because of lack of uniform definition, defining
      advanced HF precisely and, in turn, specifically assessing its epidemiology are
      difficult. However, with availability of more therapeutic options available for
      patients with advanced HF, the need to precisely define this entity is becoming
      ever more important. In general, patients with advanced HF have an extremely high
      mortality and morbidity and poor health status and quality of life. With the
      aging of the population and the worsening risk factor profile at large, for
      example, diabetes mellitus and obesity, the current epidemiological trends in
      advanced HF will likely get worse. Newer medical and device therapies as well as
      regenerative techniques hold considerable promise for these patients in future.

PMID- 21875508
TI  - Establishing prognosis in heart failure: a multimarker approach.
AB  - As a leading cause of death worldwide, predicting the progression of heart
      failure is important from the perspectives of facilitating patient and physician
      understanding of disease course and of determining the appropriate timing of the
      increasing number of medications and invasive interventions available to the
      advanced heart failure patient. Many features of a patient's history, laboratory
      findings, and imaging evaluation correlate with prognosis. This article begins
      with a review of individual markers that contribute to the risk of adverse
      events. These individual variables can be combined into multivariate models of
      outcome, most commonly expressed as life expectancy or probability of death
      within a certain time period. A representative sample of the better-validated
      models in the heart failure patient is then summarized and compared. The value in
      applying these predictors to several specific points in medical decision making
      is highlighted.

PMID- 21875509
TI  - Old and new intravenous inotropic agents in the treatment of advanced heart
      failure.
AB  - Inotropic agents are administered to improve cardiac output and peripheral
      perfusion in patients with systolic dysfunction and low cardiac output. However,
      there is evidence of increased mortality and adverse effects associated with
      current inotropic agents. These adverse outcomes may be ascribed to patient
      selection, increased myocardial energy expenditure and oxygen consumption, or to
      specific mechanisms of action. Both sympathomimetic amines and type III
      phosphodiesterase inhibitors act through an increase in intracellular cyclic
      adenosine monophoshate and free calcium concentrations, mechanisms that increase
      oxygen consumption and favor arrhythmias. Concomitant peripheral vasodilation
      with some agents (phosphodiesterase inhibitors and levosimendan) may also lower
      coronary perfusion pressure and favor myocardial damage. New agents with
      different mechanisms of action might have a better benefit to risk ratio and
      allow an improvement in tissue and end-organ perfusion with less untoward
      effects. We have summarized the characteristics of the main inotropic agents for
      heart failure treatment, the data from randomized controlled trials, and future
      perspectives for this class of drugs.

PMID- 21875510
TI  - Review of advanced heart failure device diagnostics examined in clinical trials
      and the potential benefit from monitoring capabilities.
AB  - Over the past decade, emerging clinical trial data supported the usefulness of
      implanted therapeutic cardiac devices (pacemakers and defibrillators) for the
      treatment of heart failure (HF). Interest has now developed in evaluating the
      potential of device diagnostics to identify HF patients at risk for clinical
      events and to be used in the management of HF patients. Initial studies have
      provided inconsistent results. A number of trial design elements have likely
      played a role in the lack of positive results, including cohort risk
      determination, intensity of usual care, intensity of the intervention, and
      selection of end points for the study. These issues will be important to
      understand when evaluating future clinical trial results and developing new
      studies, particularly in other HF patient cohorts such as HF with preserved left
      ventricular function.

PMID- 21875511
TI  - Surgical treatment of advanced heart failure: alternatives to heart
      transplantation and mechanical circulatory assist devices.
AB  - Although orthotopic heart transplantation is the gold standard for definitive
      surgical treatment of end-stage heart failure, other operative therapies exist
      for dealing with severe systolic left ventricular dysfunction. The choice of
      surgical intervention depends on the etiology and functional characteristics of
      the patient's ventricular dysfunction. In patients with ischemic cardiomyopathy,
      surgical revascularization improves survival. Patients with mitral regurgitation
      experience significant functional improvement from mitral valve repair and
      replacement. In patients with aortic valve dysfunction, aortic valve replacement
      results in improved survival and functional status. Although surgical ventricular
      reconstruction is controversial, significant data exist suggesting that it is an
      effective therapy in a subset of patients with left ventricular dysfunction.
      Finally, passive restraint devices are effective at halting further ventricular
      dilation. Although cardiac surgery in patients with severe ventricular
      dysfunction can be complicated by significant morbidity and mortality,
      experienced centers have demonstrated acceptable outcomes in carefully selected
      patients.

PMID- 21875512
TI  - Durable mechanical circulatory support devices.
AB  - Individuals afflicted with advanced systolic heart failure who have become
      unresponsive to standard medical and electrical therapies are categorized as
      having American Heart Association stage D heart failure. The high mortality rates
      for medically treated stage D heart failure have not improved in the last 10
      years, and patients at this advanced stage require either palliative measures or
      surgical management of heart failure. In recent years, surgically implanted
      ventricular assist devices (VADs) have become available for long-term use and are
      now commonly used as a therapy for advanced heart failure. The data generated
      from this early experience have clearly shown that VADs improve survival and
      quality of life in patients with advanced heart failure when implanted as a
      temporary measure or as long-term support. However, with a growing heart failure
      population, there is much work to be done to continually improve VAD technology,
      patient selection criteria, and postimplantation management to define the optimal
      role for assist devices in the management of systolic heart failure.

PMID- 21875513
TI  - The cardiorenal syndrome in heart failure.
AB  - The frequently occurring condition of renal failure in heart failure (HF) has
      been termed the cardiorenal syndrome. However, the importance of renal
      insufficiency in HF has only been embraced in the last decade, and therefore, the
      pathophysiology of cardiorenal failure is still poorly understood. The main
      driving force of renal failure in HF is probably hemodynamic derangement, with
      both reduced renal perfusion and increased venous pressure as the most important
      driving forces. Different cardiorenal connectors may modulate this relationship.
      Furthermore, renal failure is not only limited to reduced filtration but also
      includes glomerular hypertension and tubulointerstitial hypoxia, leading to loss
      of glomerular integrity and tubular damage. Recognition of these key
      pathophysiologic pathways in the concept of the cardiorenal syndrome is needed to
      value the interrelationship and incremental contribution of different risk
      markers and possible new treatments to improve renal function and outcome in this
      complex and bidirectional interplay between the heart and the kidney.

PMID- 21875514
TI  - Pulmonary hypertension associated with left heart disease: characteristics,
      emerging concepts, and treatment strategies.
AB  - Left heart disease (LHD) represents the most common causes of pulmonary
      hypertension (PH). Whether caused by systolic or diastolic dysfunction or
      valvular heart disease, a hallmark of PH associated with LHD is elevated left
      atrial pressure. In all cases, the increase in left atrial pressure causes a
      passive increase in pulmonary pressure. In some patients, a superimposed active
      component caused by pulmonary arterial vasoconstriction and vascular remodeling
      may lead to a further increase in pulmonary arterial pressure. When present, PH
      is associated with a worse prognosis in patients with LHD. In addition to local
      abnormalities in nitric oxide and endothelin production, gene modifiers such as
      serotonin polymorphisms may be associated with the pathogenesis of PH in LHD.
      Optimizing heart failure regimens and corrective valve surgery represent the
      cornerstone of the treatment of PH in LHD. Recent studies suggest that
      sildenafil, a phosphodiesterase-5 inhibitor, is a promising agent in the
      treatment of PH in LHD. Unloading the left ventricle with circulatory support may
      also reverse severe PH in patients with end-stage heart failure allowing
      candidacy to heart transplantation.

PMID- 21875515
TI  - Palliative care and hospice in advanced heart failure.
AB  - Advanced heart failure (HF) is a disease process that carries a high burden of
      symptoms, suffering, and death. Palliative care can complement traditional care
      to improve symptom amelioration, patient-caregiver communication, emotional
      support, and medical decision making. Despite a growing body of evidence
      supporting the integration of palliative care into the overall care of patients
      with HF and some recent evidence of increased use, palliative therapies remain
      underused in the treatment of advanced HF. Review of the literature reveals that
      although barriers to integrating palliative care are not fully understood,
      difficult prognostication combined with caregiver inexperience with end-of-life
      issues specific to advanced HF is likely to contribute. In this review, we have
      outlined the general need for palliative care in advanced HF, detailed how
      palliative measures can be integrated into the care of those having this disease,
      and explored end-of-life issues specific to these patients.

PMID- 21875517
TI  - Examination of motor and hypoalgesic effects of cervical vs thoracic spine
      manipulation in patients with lateral epicondylalgia: a clinical trial.
AB  - OBJECTIVES: The purpose of this study was to compare the effects of a cervical vs
      thoracic spine manipulation on pressure pain threshold (PPT) and pain-free grip
      strength in patients with lateral epicondylalgia (LE). METHODS: A single-blind
      randomized clinical trial was completed with 18 participants with LE. Each
      subject attended 1 experimental session. Participants were randomized to receive
      either a cervical or thoracic spine manipulation. Pressure pain threshold over
      the lateral epicondyle of both elbows pain-free grip strength on the affected arm
      and maximum grip force on the unaffected side were assessed preintervention and 5
      minutes postintervention by an examiner blind to group assignment. A 3-way
      analysis of variance with time and side as within-subject variable and
      intervention as between-subject variable was used to evaluate changes in PPT and
      pain-free grip. RESULTS: The analysis of variance detected a significant
      interaction between group and time (F = 31.7, P < .000) for PPT levels. Post hoc
      testing revealed that the cervical spine manipulation produced a greater increase
      of PPT in both sides compared with thoracic spine manipulation (P < .001). For
      pain-free grip strength, no interaction between group and time (F = .66, P = .42)
      existed. CONCLUSIONS: Cervical spine manipulation produced greater changes in PPT
      than thoracic spine manipulation in patients with LE. No differences between
      groups were identified for pain-free grip. Future studies with larger sample
      sizes are required to further examine the effects of manipulation on mechanisms
      of pain and motor control in upper extremity conditions.

PMID- 21875516
TI  - Relationships between joint motion and facet joint capsule strain during cat and
      human lumbar spinal motions.
AB  - OBJECTIVE: The lumbar facet joint capsule (FJC) is innervated with mechanically
      sensitive neurons and is thought to contribute to proprioception and pain.
      Biomechanical investigations of the FJC have commonly used human cadaveric
      spines, whereas combined biomechanical and neurophysiological studies have
      typically used nonhuman animal models. The purpose of this study was to develop
      mathematical relationships describing vertebral kinematics and FJC strain in cat
      and human lumbar spine specimens during physiological spinal motions to
      facilitate future efforts at understanding the mechanosensory role of the FJC.
      METHODS: Cat lumbar spine specimens were tested during extension, flexion, and
      lateral bending. Joint kinematics and FJC principal strain were measured
      optically. Facet joint capsule strain-intervertebral angle (IVA) regression
      relationships were established for the 3 most caudal lumbar joints using cat
      (current study) and human (prior study) data. The FJC strain-IVA relationships
      were used to estimate cat and human spine kinematics that corresponded to
      published sensory neuron response thresholds (5% and 10% strain) for low
      threshold mechanoreceptors. RESULTS: Significant linear relationships between IVA
      and strain were observed for both human and cat during motions that produced
      tension in the FJCs (P < .01). During motions that produced tension in the FJCs,
      the models predicted that FJC strain magnitudes corresponding to published
      sensory neuron response thresholds would be produced by IVA magnitudes within the
      physiological range of lumbar motion. CONCLUSIONS: Data from the current study
      support the proprioceptive role of lumbar spine FJC and low-threshold
      mechanoreceptive afferents and can be used in interpreting combined
      neurophysiological and biomechanical studies of cat lumbar spines.

PMID- 21875518
TI  - Effects of nerve mobilization exercise as an adjunct to the conservative
      treatment for patients with tarsal tunnel syndrome.
AB  - OBJECTIVE: This study was carried out with the aim of investigating the
      contribution of nerve mobilization exercises to the conservative treatment of
      tarsal tunnel syndrome. METHODS: In this clinical trial, 28 patients were
      randomly allocated into 2 groups. The control group was composed of 14 patients
      who were treated conservatively with a program consisting of physiotherapy and
      supportive inserts, whereas 14 patients in the study group were given nerve
      mobilization exercises in addition to the same treatment. Allpatients were
      followed up for 6 weeks. Before treatment, subjects were evaluated for muscle
      strength, range of motion, pain, sensory tests, and clinical manifestations of
      tarsal tunnel syndrome. The evaluations were repeated after 6 weeks. RESULTS:
      There was a significant difference in favor of posttreatment values for range of
      motion, muscle strength, and pain in both groups (P < .05). Intergroup
      comparisons showed no difference between the groups for these parameters.
      Significant results were attained in the study group for 2-point discrimination
      and light touch and Tinel sign after treatment (P < .05). CONCLUSION: Patients in
      both groups showed improvement from conservative treatment. The results of the
      study group showed that nerve mobilization exercises have a positive effect on 2
      point discrimination and light touch and Tinel sign.

PMID- 21875519
TI  - Short-term effects of neurodynamic mobilization in 15 patients with secondary
      thumb carpometacarpal osteoarthritis.
AB  - OBJECTIVE: The purpose of this study is to evaluate whether neurodynamic
      mobilization of the median nerve improves pressure pain threshold (PPT) and pinch
      and grip strength in patients with secondary thumb carpometacarpal osteoarthritis
      (TCOA). METHOD: Fifteen patients with secondary TCOA (13 women and 2 men) between
      70 and 90 years old were received by neurodynamic therapy. All patients received
      median nerve mobilization of the dominant hand by sliding technique during 4
      sessions over 2 weeks. The outcome measures of this case series were monitored by
      using PPT measured by algometry as PPT at the trapeziometacarpal (TM) joint,
      tubercle of the scaphoid bone, and the unciform apophysis of the hamate bone. Tip
      and tripod pinch strength was also measured. Grip strength was measured by a grip
      dynamometer. These variables were measured at pretreatment, 5 minutes
      posttreatment, 1 week (first follow-up [FU]) and 2 weeks after treatment (second
      FU). RESULTS: Pressure pain threshold in the TM joint was 3.54 +/- 0.04 kg/cm(2).
      After treatment, it increased to 4.38 +/- 0.04 kg/cm(2) (P < .01) and maintained
      in the first FU (4.27 +/- 0.04 kg/cm(2), P < .02) and second FU (4.08 +/- 0.04
      kg/cm(2), P < .02). In contrast, we found no differences in PPT in the other
      studied structures after treatment. Similarly, tip and tripod pinch strength
      remained without change after treatment. Grip strength was 10.77 +/- 0.18 kg, and
      after treatment, it increased to 11.55 +/- 0.16 kg (P < .05) and maintained in
      first FU (11.73 +/- 0.18 kg, P < .02) and second FU (11.2 +/- 0.17 kg, P < .05).
      CONCLUSIONS: Median nerve mobilization decreased pain in the TM joint and
      increased grip strength in this group of patients with TCOA.

PMID- 21875520
TI  - An exploratory thermographic investigation of the effects of connective tissue
      massage on autonomic function.
AB  - OBJECTIVE: The purpose of this study was to measure effects of connective tissue
      massage (CTM) on the autonomic nervous system using thermography and
      physiological measurements. METHODS: A repeated-measures design was used. The
      setting was a university laboratory. Skin temperature at the site of massage,
      blood pressure, heart rate, and dorsal foot temperature were measured in 8
      healthy participants before CTM, immediately after, and at 15-minute intervals
      for 1 hour. RESULTS: The effect of CTM on skin temperature was statistically
      significant, P = .011. Post hoc pairwise comparisons revealed that the 15-, 30-,
      45-, and 60-minute data all differed significantly from the pre-CTM data (all P <
      .05) and also from the immediately post-CTM data (all P < .05). For diastolic
      blood pressure, the main analysis of variance showed a statistical significance
      at P = .062. For other variables, there was no evidence for an effect.
      CONCLUSIONS: Evidence was seen of some effects of CTM on autonomic function. This
      is information that will increase our knowledge of how CTM affects the autonomic
      nervous system.

PMID- 21875521
TI  - Morphological asymmetry of the atlas and its clinical implications.
AB  - OBJECTIVE: The aim of this study was to investigate the asymmetry of the adult
      atlas by deviation frequencies using 3-dimensional (3D) computer models based on
      the computed tomographic (CT) spine data from healthy patients. METHODS: Sixty
      adult atlas computer models were reconstructed from CT data of the cervical
      spine. The morphological asymmetries were investigated and measured with 3D
      software. Asymmetry in the morphology of the vertebral artery groove was
      observed, and the angles between the lines connecting the apices of transverse
      processes and the apices of anterior and posterior tubercles were measured. The
      lengths of the left and right posterior arches were measured, and the differences
      in values were categorized. RESULTS: We observed 7 cases (11.67%) with
      asymmetrical vertebral artery groove forms. There were 4 different categories:
      foramen-shaped, semi-foramen-shaped, deep, and superficial grooves. The asymmetry
      was of different shapes on both sides. Relative to the lines connecting the
      apices of anterior and posterior tubercles, the asymmetry frequency of the
      transverse processes and the posterior arch length was 6.67% and 16.67%,
      respectively. CONCLUSIONS: For the specimens in this study, variation in
      morphology of the atlas was common. Asymmetry of apices of transverse processes,
      posterior arches, and vertebral artery grooves should be taken into account
      during clinical palpation, diagnostic imaging, and treatment including spinal
      manipulation.

PMID- 21875522
TI  - Use of a computer interviewing system in a chiropractic clinic during periodic
      patient reassessment.
AB  - OBJECTIVE: The purpose of this study was to investigate whether a computer
      interviewing system (CIS) could be used as part of the periodic patient
      reassessment process, if patients and practitioners perceived that the CIS
      enhanced communication, and if the CIS could be used to identify patients with
      possible anxiety and/or depression. METHODS: An observational method was used,
      whereby the CIS was used to augment the usual patient reassessment routine in a
      chiropractic clinic. One clinic in the Dundee region, with 3 chiropractors,
      collected information from 60 patients using a CIS directly before the patient
      treatment session. The patients were then asked to rate whether they had
      disclosed new information relative to their care, if they felt better prepared,
      or if it had helped them to formulate questions. The chiropractors reported
      whether the interview transcript was useful, if it helped to identify
      communication issues, and if it had altered the treatment session. RESULTS: The
      doctors of chiropractic rated the interview transcript as useful for 83% of
      patients, they altered the treatment session for 20% of patients, and the CIS
      helped to identify communication difficulties for 13% of patients. The
      chiropractors were surprised by the Hospital Anxiety and Depression Scale results
      for 23% of patients. The patients were positive about the inclusion of the CIS,
      with 42% saying that they disclosed new information and 33% saying that they felt
      better prepared for the session with the chiropractor after having used the CIS.
      The CIS was acceptable to 90% of patients. CONCLUSIONS: The inclusion of the CIS
      at this one clinic appeared to be a useful addition to the periodic patient
      reassessment process and was perceived to be an efficient media to evaluate
      Hospital Anxiety and Depression Scale scores.

PMID- 21875523
TI  - Complementary and alternative medicine in the treatment of pain in fibromyalgia:
      a systematic review of randomized controlled trials.
AB  - OBJECTIVE: The purpose of this study was to systematically review the literature
      for randomized trials of complementary and alternative medicine (CAM)
      interventions for fibromyalgia (FM). METHODS: A comprehensive literature search
      was conducted. Databases included the Cochrane library, PubMed, PsycINFO,
      Cumulative Index to Nursing and Allied Health, Natural Medicines Comprehensive
      Database Manual, Alternative and Natural Therapy Index System (MANTIS), Index for
      Chiropractic Literature, and Allied and Complementary Medicine (AMED). Inclusion
      criteria were (a) subjects were diagnosed with fibromyalgia and (b) the study
      design was a randomized controlled trial that compared a CAM therapy vs a control
      group. Studies were subgrouped by CAM treatment into 11 categories. Evidence
      tables and forest plots were organized to display quality ratings and effect
      sizes of each study. RESULTS: The literature search yielded 1,722 results; 102
      abstracts were selected as potential articles for inclusion. Sixty studies met
      criteria and were rated by 2 reviewers; 18 were rated as good quality; 20,
      moderate; 18, low; and 4, very low. Synthesis of information for CAM categories
      represented by more than 5 studies revealed that balneotherapy and mind-body
      therapies were effective in treating FM pain. This study analyzed recent studies
      and focused exclusively on randomized controlled trials. Despite common use of
      manual therapies such as massage and manipulation to treat patients with FM,
      there is a paucity of quality clinical trials investigating these particular CAM
      categories. CONCLUSION: Most of these studies identified were preliminary or
      pilot studies, thus had small sample sizes and were likely underpowered. Two CAM
      categories showed the most promising findings, balneotherapy and mind-body
      therapies. Most of the other CAM categories showed a trend favoring the treatment
      group. It appears that several CAM therapies show some preliminary treatment
      effect for FM pain, but larger trials that are more adequately powered are
      needed.

PMID- 21875524
TI  - Disclosure of conflict of interest.

PMID- 21875525
TI  - Conflict of interest.

PMID- 21875526
TI  - Correcting some errors.

PMID- 21875527
TI  - Can the fragment stability of osteochondritis dissecans be interpreted by
      arthroscopic findings alone?

PMID- 21875528
TI  - Dynamic imaging and function of partial supraspinatus tendon tears.
AB  - PURPOSE: It was the purpose of this study to identify and document normal and
      abnormal supraspinatus tendon function in vivo using real-time ultrasound.
      METHODS: We defined 4 groups of 20 individuals each: partial tear (group 1), full
      thickness tear (group 2), successfully repaired tear (group 3), and healthy
      asymptomatic controls (group 4). Except for group 4, all patients underwent
      magnetic resonance arthrography to confirm the diagnosis. All underwent
      ultrasound imaging of the supraspinatus tendon with the adducted arm at rest and
      under maximal isometric abduction. Tendon deformation was dynamically assessed
      and measured with tendon thickness changes at 0.5, 1, 1.5, and 2 cm from the
      tendon insertion. The clinical assessment consisted of absolute and relative
      Constant score, subjective shoulder value, and strength measurements. RESULTS:
      Without muscle contraction, the tendons of the 4 groups were not of significantly
      different thickness, with the least variation at 1.5 cm from the insertion site.
      On contraction, the normal tendon thickness significantly increased at a distance
      of 2 cm, whereas it did not for the full-thickness and partial supraspinatus
      tears. Thus contraction of the muscle resulted in measurable deformation of the
      tendon. CONCLUSIONS: Partially torn supraspinatus tendons can be functionally
      incompetent, leading to a biomechanical deformation of the musculotendinous unit
      that is not different from that of a unit with a full-thickness tendon tear. The
      dynamic sonographic finding of a successful repair of a supraspinatus tendon is
      similar to that of a normal tendon, even though the previously injured muscle
      appears unable to generate the same strength as a normal muscle. LEVEL OF
      EVIDENCE: Level III, case-control study.

PMID- 21875529
TI  - The effects of hamstring harvesting on outcomes in anterior cruciate ligament
      reconstructed patients: a comparative study between hamstring-harvested and 
      unharvested patients.
AB  - PURPOSE: The purpose of this study was to evaluate the effects of hamstring
      harvesting in patients after anterior cruciate ligament (ACL) reconstruction by
      comparing groups with and without hamstring harvesting. METHODS: We evaluated the
      effect of hamstring harvesting in 73 consecutive patients who underwent ACL
      reconstruction: 39 patients whose hamstrings were harvested for autografts (group
      H) were compared with 34 patients who received allografts during the same time
      period (group C [control]). The cases and controls were compared by analyzing the
      following variables: age, height, weight, mean follow-up period, type of tissue
      used, and meniscal surgery. Outcomes were assessed by the Lysholm knee score,
      Tegner activity score, and KT-2000 side-to-side difference (MEDmetric, San Diego,
      CA), as well as functional performance tests. The flexor deficit and isokinetic
      peak torque for knee flexion were measured in the sitting position (0 degrees  to
      90 degrees ), and the flexion torque at 90 degrees  was measured in the prone
      position (60 degrees  to 120 degrees ). RESULTS: Although significant knee
      flexion weakness after ACL reconstruction was observed, a significantly greater
      knee flexor deficit was found in autograft patients than in allograft patients (P
      < .001). No differences were found between groups in terms of clinical and
      functional results regardless of hamstring harvesting. The performance of both
      study groups in all 4 functional tests were significantly correlated with flexor
      deficit in the sitting position (P < .05) but not in hyperflexion. Significant
      flexor deficits in both normal and hyperflexed positions were noted in both
      groups when compared with the unaffected knee (group H, P < .001; group C, P =
      .002). CONCLUSIONS: These results indicate significant knee flexion weakness
      compared with the unaffected knee after ACL reconstruction regardless of
      hamstring harvesting. Moreover, the greater increase in knee flexor deficit in
      the hamstring-harvested group compared with the allograft group was statistically
      significant. However, clinical and functional outcomes were similar between the
      groups. LEVEL OF EVIDENCE: Level III, case-control study.

PMID- 21875530
TI  - Engineering and design.

PMID- 21875531
TI  - Membranes.

PMID- 21875532
TI  - On the cover--Aspergillus niger.

PMID- 21875533
TI  - Do we have evidence that pediatric written asthma action plans really work?

PMID- 21875534
TI  - Allergy and the bone: connections.

PMID- 21875535
TI  - The 10-second rule and other myths about epinephrine and autoinjectors.

PMID- 21875536
TI  - Spice allergy.
AB  - OBJECTIVES: To provide a review on spice allergy and its implementation in
      clinical practice. DATA SOURCES: PubMed searches were performed using spice
      allergy as the keyword for original and review articles. Selected references were
      also procured from the reviewed articles' references list. STUDY SELECTION:
      Articles were selected based on their relevance to the topic. RESULTS: Spices are
      available in a large variety and are widely used, often as blends. Spice allergy
      seems to be rare, reportedly affecting between 4 and 13 of 10,000 adults and
      occurring more often in women because of cosmetic use. No figures were available
      on children. Most spice allergens are degraded by digestion; therefore, IgE
      sensitization is mostly through inhalation of cross-reacting pollens,
      particularly mugwort and birch. The symptoms are more likely to be respiratory
      when exposure is by inhalation and cutaneous if by contact. Studies on skin
      testing and specific IgE assays are limited and showed low reliability. The
      diagnosis primarily depends on a good history taking and confirmation with oral
      challenge. The common use of spice blends makes identifying the particular
      offending component difficult, particularly because their components are
      inconsistent. CONCLUSION: Spices are widely used and contain multiple allergens,
      yet spice allergy is probably markedly underdiagnosed. There is a need for
      reliable skin testing extracts and serum specific IgE assays. Currently, the
      diagnosis depends on a good history taking and well-designed titrated challenge
      testing. Until immunotherapy becomes developed, treatment is strict avoidance,
      which may be difficult because of incomplete or vague labeling.

PMID- 21875537
TI  - Allergy and the bone: unexpected relationships.
AB  - OBJECTIVE: To examine the relationships between allergy and bone metabolism as
      represented by the effects of antihistamines and leukotriene modifiers on bone
      resorption and formation. DATA SOURCES: The major databases MEDLINE and Scopus
      were searched using the keywords bone metabolism, bone resorption, bone
      formation, antihistamines, h1 antagonist, leukotriene antagonist, and leukotriene
      modifier. STUDY SELECTION: The studies were independently evaluated by all the
      coauthors, who judged their pertinence to this review. RESULTS: Two of the most
      intriguing aspects in the field are the possible effects of leukotriene modifiers
      on fracture repair and the hypothesized role of antihistamines in contrasting
      osteoporosis. Another rapidly expanding field of research is that related to the
      immune-modulating effects of vitamin D because serum levels of vitamin D have
      been shown to correlate with pulmonary function, asthma onset, and the
      development of allergic diseases. CONCLUSION: Although unexpected, data are now
      available suggesting a strict connection among allergy, its treatments, and bone
      metabolism.

PMID- 21875538
TI  - Written action plan use in inner-city children: is it independently associated
      with improved asthma outcomes?
AB  - BACKGROUND: Guidelines from the National Asthma Education and Prevention Program
      stipulate that multicomponent self-management interventions for asthma should
      include a written action plan (WAP). However the specific, independent effect of
      WAPs in improving outcomes remains unclear. OBJECTIVE: To measure the association
      between WAP use during the previous year and improved asthma outcomes. METHODS:
      We conducted a longitudinal quasi-experimental study using data from the Healthy
      Homes II (HH-II) randomized controlled trial in Seattle, WA. Action plan use
      during the previous year was measured at exit of HH-II. A participant was a WAP
      user if he used his action plan every day, almost every day, or once per week,
      and non-user if he did not meet these criteria. Sensitivity analyses explored
      less stringent criteria for WAP user designation. Prespecified outcomes were
      baseline-to-exit changes in asthma control in the previous 2 weeks, Pediatric
      Asthma Caregiver Quality of Life Scale score, and urgent health services
      utilization. We used robust linear and logistic regression to compare outcomes
      across groups. RESULTS: Two hundred fifty-one patients participated: 112 WAP
      users; 139 non-users. After adjustment, no significant differences in outcomes
      were observed between WAP users and non-users. Among a subgroup of participants
      with recent urgent health services utilization, WAP users had better asthma
      control than non-users. Changing WAP user criteria to include those who simply
      owned an action plan, irrespective of use, did not alter our results. CONCLUSION:
      WAP use during the previous year was not associated with improved outcomes
      compared with non-use. Additional studies are needed to assess the long-term,
      independent benefit of this universally recommended intervention.

PMID- 21875540
TI  - Urban-rural differences in asthma prevalence among young people in Canada: the
      roles of health behaviors and obesity.
AB  - BACKGROUND: Asthma prevalence has been reported to be lower in rural regions, but
      the reasons for this are not known. OBJECTIVE: To confirm the existence of an
      urban-rural geographic gradient in asthma prevalence among Canadian youths and to
      evaluate whether this gradient was mediated by health behaviors. METHODS: Cross
      sectional data from 4,726 Canadian youth (grades 6-10) were collected during the
      2001-02 Health Behaviour in School-Aged Children survey. Geographic region was
      categorized as metro (urbanized), non-metro but adjacent to metro, and rural.
      Asthma was defined via self-report of doctors' diagnoses and at least 1 of: (1)
      asthma symptoms or (2) a health care visit for asthma in the past year. Health
      behaviors (diet and physical activity) as well as obesity were also assessed.
      RESULTS: Asthma prevalence was lowest in rural regions (metro = 17.7%, non-metro
      adjacent = 15.6%, rural = 14.8%). A lower risk of asthma was associated with
      rural region (adjusted odds ratio [OR] = 0.76, 95% CI = 0.61-0.95) and living in
      non-metro-adjacent regions (adjusted OR = 0.81, 95% CI = 0.65-1.01). Health
      behaviors and obesity status did not mediate the association between geographic
      region and asthma. Being overweight or obese, having a high physical activity
      level, and exposure to passive smoking independently elevated the risk of asthma,
      whereas increased consumption of whole milk or vegetables were each protective.
      CONCLUSIONS: Although asthma prevalence among youth was lower in rural areas,
      this association was not mediated by health behaviors or obesity. Other
      exposures, likely environmental, are the logical mechanisms through which rural
      geographic status is related to lower asthma prevalence.

PMID- 21875539
TI  - Association of ozone exposure with asthma, allergic rhinitis, and allergic
      sensitization.
AB  - BACKGROUND: Children are vulnerable to air pollution, which is known to be
      related to the recent increasing trend of allergic disease. OBJECTIVE: To
      investigate the effects of air pollution on respiratory allergic diseases in
      school children. METHODS: A prospective survey of parental responses to
      International Study of Asthma and Allergies in Childhood questionnaires, together
      with allergy evaluation, was conducted in 1743 school children selected from
      metropolitan cities and industrial areas during a 2-year period. Individual
      exposure to air pollution was estimated by using a geometric information system
      with the 5-year mean concentration of air pollutants. RESULTS: A total of 1,340
      children (male:female ratio, 51.4:48.6) with a mean (SD) age of 6.84 (0.51) years
      were included in the analysis. Each child underwent allergy evaluation at the
      time of enrollment and at a 2-year follow-up. After 2 years, the 12-month
      prevalence of wheezing was significantly decreased, whereas the lifetime
      prevalence of allergic rhinitis showed a significant increase. Ozone exposure was
      significantly associated with the 12-month prevalence of wheeze (odds ratio per 5
      ppb, 1.372; 95% confidence interval, 1.016-1.852). Ozone was also associated with
      allergic rhinitis in children who reside in industrial areas. In addition,
      significant positive associations between ozone and the rate of newly developed
      sensitization to outdoor allergen were found (P for trend = .007). CONCLUSION:
      Exposure to ozone was associated with current wheeze and allergic rhinitis. An
      increased rate of newly developed sensitization to outdoor allergen by ozone may
      explain the association.

PMID- 21875541
TI  - Accuracy of eucapnic hyperpnea or mannitol to diagnose exercise-induced
      bronchoconstriction: a systematic review.
AB  - BACKGROUND: Exercise challenge testing is the typical method for diagnosing
      exercise induced bronchoconstriction; however, alternate tests have been
      developed. OBJECTIVE: The purpose of this paper was to summarize the current
      literature comparing eucapnic voluntary hyperpnea and mannitol with standard
      exercise challenge testing to determine whether either test is a suitable
      alternative to standard exercise testing for the diagnosis of exercise-induced
      bronchoconstriction. METHODS: Using valid systematic review methods, a
      comprehensive search strategy to avoid publication bias, we identified 10 studies
      that compared exercise challenge testing with either eucapnic voluntary hyperpnea
      or mannitol. RESULTS: For the 7 diagnostic cross-sectional studies that examined
      eucapnic voluntary hyperpnea, the sensitivity and specificity values were
      heterogeneous, ranging from 25 to 90% for sensitivity and 0 to 71% for
      specificity. In the 3 diagnostic cross-sectional studies that evaluated mannitol,
      the sensitivity and specificity ranged from 58 to 96% and 65 to 78%,
      respectively. For most studies, a representative spectrum of participants being
      tested was not used. CONCLUSION: Given the heterogeneity in sensitivity and
      specificity of eucapnic voluntary hyperpnea studies and the relatively small
      number of studies that have examined mannitol, insufficient evidence is available
      to conclude that either of these tests are suitable alternatives to exercise
      challenge testing to detect exercise-induced bronchoconstriction. Additional
      research is required.

PMID- 21875542
TI  - The TEN study: time epinephrine needs to reach muscle.
AB  - BACKGROUND: An epinephrine autoinjector (EAI) is designed to deliver epinephrine
      into the vastus lateralis muscle. Several studies have demonstrated both patient
      and physician difficulties in correctly using EAIs, specifically premature
      removal of the device from the thigh. OBJECTIVE: To evaluate the correlation
      between duration of injection with an EAI and amount of epinephrine absorbed into
      muscle tissue. METHODS: Twenty-one EAI devices (0.3 mL) were used to determine
      the amount of epinephrine injected into marbleized beef during 7 time periods. A
      digital scale was used to record preinjection and postinjection weights of EAIs
      and beef. The weight difference between the preinjection and postinjection
      periods of the EAIs was used to calculate the total amount of epinephrine
      released and available for absorption into the marbleized beef. The difference
      between the preinjection and postinjection beef weight was used to determine the
      amount of epinephrine absorbed into the meat. RESULTS: The correlation with
      duration of injection for both the amount of epinephrine absorbed and released
      was 0.321 (P = .48). At all intervals, 95.9% or more of epinephrine was absorbed
      into the marbleized beef. The correlation with duration of injection and percent
      of epinephrine absorbed was 0.464 (P = .29). There were no time periods that were
      significantly different from the percentage of epinephrine absorbed by the
      marbleized beef at 10 seconds (analysis of variance P = .16). CONCLUSION: No
      linear relationship between time and amount of epinephrine injected or absorbed
      into muscle tissue was demonstrated. These data suggest that holding the device
      in place for 1 second is as effective as 10 seconds.

PMID- 21875543
TI  - Utility of routine laboratory testing in management of chronic
      urticaria/angioedema.
AB  - BACKGROUND: Laboratory tests are routinely ordered to identify or rule out a
      cause in patients with chronic urticaria/angioedema (CUA). The results of these
      tests are usually within normal limits or unremarkable. OBJECTIVE: To investigate
      the proportion of abnormal test results in patients with CUA leading to a change
      in management and in outcomes of care. METHODS: Retrospective analysis of a
      random sample of adult patients with CUA from 2001-2009. RESULTS: Cases totaled
      356: 166 with urticaria and angioedema (AE), 187 with urticaria, and 3 with only
      AE. Patients were predominately women (69.1%) and white (75.6%), with a mean age
      of 48 +/- 15 years. Abnormalities were commonly seen in complete blood counts
      (34%) and in complete metabolic panels (9.4%). Among the 1,872 tests that were
      ordered, results of 319 (17%) were abnormal. Of 356 patients, 30 underwent
      further testing because of abnormalities in laboratory work. This represented 30
      of 1,872 tests (1.60%). Only 1 patient benefited from a subsequent change in
      management. CONCLUSIONS: Laboratory testing in CUA patients referred for an
      Allergy and Immunology evaluation rarely lead to changes in management resulting
      in improved outcomes of care.

PMID- 21875544
TI  - Determination of ranges for reporting pollen aeroallergen levels in the
      Washington, DC, metropolitan area.
AB  - BACKGROUND: Local aeroallergen monitoring provides useful information for the
      atopic patient and medical community. Currently, National Allergy Bureau (NAB)
      ranges are used for reporting pollen count levels in the Washington, DC, area.
      OBJECTIVE: To determine standard range criteria (low, moderate, high, and very
      high) for the reporting of specific tree, grass, and weed aeroallergens
      representative of the Washington, DC, metropolitan region. METHODS: Atmospheric
      sampling for pollen aeroallergens was performed using a volumetric rotating-arm
      impaction sampler (model 40 Rotorod, SDI Company, Plymouth Meeting, PA). The
      cumulative pollen count, over a 12-year period (1998-2009), was determined for
      specific pollen aeroallergens. Local ranges were developed using methodology
      previously employed to determine NAB ranges. A comparison was made between NAB
      and Washington, DC, area ranges. RESULTS: The local median count, and low and
      moderate range criteria, are markedly lower than NAB range counts for tree,
      grass, and weed pollen. The NAB 99th percentile (high) count is significantly
      higher for grass and weed pollen but lower for tree pollen. Using new local range
      criteria, an increase was seen in the number of high days recorded for weed
      pollen (1,300%), grass pollen (258.6%), and tree pollen (11.8%). Previously,
      using NAB range criteria, no very high days were reported for grass and weed
      pollen over the 12-year period. CONCLUSION: Washington, DC, ranges establish more
      relevant reporting standards for our local patient population and will allow for
      comparison with reporting levels developed for sampling locations nationwide as
      well as with other regional sites.

PMID- 21875545
TI  - Glucocorticoid-induced immunoglobulin E synthesis by peripheral blood mononuclear
      cells from allergic and nonallergic subjects.
AB  - BACKGROUND: Glucocorticoids (GCS) have been shown to induce IgE synthesis in
      human peripheral blood mononuclear cells (PBMCs) and purified B cells in vitro.
      However, the differences in immunoglobulin E (IgE) response to GCS between
      allergic and non-allergic individuals and the mechanism this interaction have not
      been elucidated. OBJECTIVE: We aimed to compare the effect of GCS (budesonide) on
      interleukin (IL)-4-driven IgE production in vitro in allergic and non allergic
      subjects and assess the engagement of intracellular mechanisms. METHODS: The
      study included 22 patients with allergic asthma and/or allergic rhinitis and 24
      healthy volunteers. PBMCs were cultured for 11 days with IL-4 and budesonide and
      IgE concentrations in supernatants were assessed by immunoassays. T and B cell
      markers were assessed by flow cytometry. RESULTS: Budesonide enhanced IgE
      synthesis to higher extent in healthy donors than in allergic patients (mean
      increase of 16.5 vs 6.3 kU/L, P< .05 respectively) acting through glucocorticoid
      receptor. Budesonide significantly increased lymhoplasmocytoid cells percentage
      in both media-controlled (2.5-fold increase) and IL-4-stimulated PBMCs (2-fold
      increase). Added to IL-4 budesonide decreased the percentage of both T cells and
      CD40L(+) T cells, but strongly increased the percentage of B cells. Protein
      tyrosine kinase (PTK) inhibitor decreased, but NF-kappaB and protein kinase A
      (PKA) inhibitors expressed modulatory effects on budesonide-induced IgE
      synthesis. CONCLUSIONS: Budesonide-induced IgE generation in PBMCs differs in
      magnitude and seems to involve different mechanisms in atopic and non-atopic
      subjects.

PMID- 21875546
TI  - Efficacy of budesonide/formoterol pressurized metered-dose inhaler versus
      budesonide pressurized metered-dose inhaler alone in Hispanic adults and
      adolescents with asthma: a randomized, controlled trial.
AB  - BACKGROUND: Few clinical trials in asthma have focused on Hispanic populations.
      OBJECTIVE: To compare the efficacy and safety of budesonide/formoterol (BUD/FM)
      with BUD in an ethnically diverse group of Hispanic participants with asthma
      previously treated with inhaled corticosteroids (ICS). METHODS: This 12-week,
      randomized, double-blind, active-controlled study (NCT00419757) was designed to
      enroll Hispanic participants (self-reported) (>=12 years of age) with moderate to
      severe asthma requiring medium- to high-dose ICS. After a 2-week run-in period
      (low-dose BUD pressurized metered-dose inhaler [pMDI] 80 MUg * 2 inhalations [160
      MUg] twice daily), participants with a symptom score greater than 0 (scale: 0-3)
      on 3 or more of 7 run-in days and forced expiratory volume in 1 second (FEV(1))
      45%-85% predicted were randomized to BUD/FM pMDI 160/4.5 MUg * 2 inhalations
      (320/9 MUg) twice daily or BUD pMDI 160 MUg * 2 inhalations (320 MUg) twice
      daily. RESULTS: Randomized participants (n = 127 BUD/FM; n = 123 BUD) were
      predominately Mexican (51%) or Puerto Rican (21%). During low-dose ICS run-in,
      the mean symptom score was 1.0; however, mean predose FEV(1) improved (2.10-2.21
      L). During randomized treatment, small, but not statistically significant,
      improvements favored BUD/FM vs BUD (am peak expiratory flow [PEF; primary
      efficacy variable] 25.4 vs 19.9 L/min; pm PEF 20.6 vs 15.8 L/min; predose FEV(1)
      0.16 vs 0.11 L; rescue medication use -0.7 vs -0.6 inhalations/d). Most adverse
      events were mild or moderate in intensity. CONCLUSIONS: Improvement in clinically
      relevant control end points occurred in both BUD/FM and BUD groups; both
      treatments were well tolerated in this Hispanic asthma population but were not
      significantly differentiated.

PMID- 21875547
TI  - The effects of inhaled formoterol on the autonomic nervous system in adolescents
      with asthma.
AB  - BACKGROUND: The safety of long-acting beta-2-adrenergic agonists is increasingly
      questioned by physicians. Although formoterol is frequently used in childhood,
      its effects on the autonomic cardiovascular system have not been studied.
      OBJECTIVE: To investigate the effects of inhaled formoterol on autonomic nervous
      system using heart rate variability in adolescents with persistent asthma.
      METHODS: Electrocardiography of 20 asthmatic adolescents (12-20 years) was
      monitored for 5 specific days. The first day served as basal measurement, and the
      2nd and 3rd days reflected the effects of a single and 2 doses of formoterol,
      respectively. From days 4 to 29, patients received regular treatment with
      formoterol/budesonide and were monitored on days 30 and 31 to evaluate the
      development of cardiac and respiratory tolerance after single-dose and 2 doses of
      formoterol, respectively. Electrocardiographs were analyzed for heart rate, heart
      rate variability (both time and frequency domain parameters), and spirometry
      tests were performed. RESULTS: Inhalation of single-dose formoterol increased
      heart rate and decreased heart rate variability parameters (ratio of the normal
      to-normal [NN] interals changing in excess of 50 ms to total of NN intervals
      [pNN50], total power [TP][ms], TP[ln]) compared with the corresponding baseline
      values during the first 12 hours of the day. The heart rate variability
      parameters (pNN50, TP[ms], TP[ln], root mean square of differences between
      adjacent NN intervals) during the first 12 hours were increased on the 30th day
      compared with the 2nd day and decreased on the 31st day compared with the 30th
      day. CONCLUSION: Single-dose formoterol inhalation decreases cardiovagal
      responsiveness and increases the sympathetic tone in cardiac autonomous control,
      and regular use of formoterol causes development of tolerance to these effects.
      However, additive doses of formoterol cause loss of this tolerance.

PMID- 21875548
TI  - Development of the Asthma Control Composite outcome measure to predict omalizumab
      response.
AB  - BACKGROUND: Previous assessments of response to omalizumab were based on diary
      based data rather than standard validated instruments. A composite instrument
      that translates diary-based data into standard validated asthma control measures
      would characterize patient response to treatment in terms of current asthma
      control definitions. OBJECTIVE: To develop the Asthma Control Composite (ACC)
      tool, using real-time diary-based data to predict treatment response in terms of
      asthma control. METHODS: The ACC tool was derived retrospectively using pooled
      data from two phase 3 studies in patients with moderate to severe allergic
      asthma. Patients were randomized to receive subcutaneous omalizumab or placebo
      for 16 weeks plus stable beclomethasone dipropionate therapy, followed by a 3
      month corticosteroid reduction period and 5-month double-blind safety extension.
      Control was assessed as "complete," "good," or "not controlled," based on a
      composite score of 4 elements: rescue medication (puffs/day), total asthma
      symptom score, average number of awakening nights/28 days, and activity
      limitation. RESULTS: The ACC was mapped to standard validated measures of patient
      reported outcomes, with results consistent with clinical outcomes. The proportion
      of patients with baseline uncontrolled asthma achieving "good" or "complete"
      asthma control was 48% with omalizumab and 32% with placebo at approximately 4
      months. The mean composite score also was improved with omalizumab (3.52) vs
      placebo (2.56) at approximately 4 months. CONCLUSIONS: The ACC tool accurately
      reflects asthma control in moderate to severe asthma patients eligible for
      biological therapy. Unlike the ACT, which has not been validated in this patient
      population, the ACC shows promise as an asthma control assessment tool in
      patients with moderate to severe asthma.

PMID- 21875549
TI  - Eosinophilia in conjunctival tear fluid among patients with pollen allergy.

PMID- 21875550
TI  - Cosensitization to orange seed and cashew nut.

PMID- 21875551
TI  - A patient with salmon roe allergy showing taxonomy-unrelated cross-reactivity
      with sea urchin roe.

PMID- 21875552
TI  - Severe angioedema associated with olmesartan.

PMID- 21875554
TI  - Novel epinephrine auto-injector (NEA): sharps injury prevention validation and
      comparable analysis with EpiPen and Twinject.

PMID- 21875555
TI  - Predictive marker of bronchial impairment.

PMID- 21875557
TI  - Special Issue on the 2010 Conference on Medical Image Computing and Computer
      Assisted Intervention. Editorial.

PMID- 21875558
TI  - Off-label prescriptions: patient safety first.

PMID- 21875561
TI  - Mast cells in nonmammalian vertebrates: an overview.
AB  - Mast cells are best known as multifunctional entities that may confer a benefit
      on immune system. This review presents the known facts on mast-cell system and
      breakthroughs in mast-cell biology in fish, amphibians, reptiles, and birds. As
      compared to mammals, there are relatively few data available on mast cells in
      many nonmammalian vertebrates. Nevertheless, like in mammals, mast cells in
      nonmammalian vertebrates contain a wide range of bioactive compounds including
      histamine, heparin, neuropeptides, and neutral proteases. In bony fishes, these
      cells secrete antimicrobial peptides as well. Mast cells have a widespread
      distribution in the brain, endocrine glands, intestine, liver, kidney, skin,
      tongue, and lungs, the highest concentration occurring in different tissues in
      the different taxa. Currently, researchers are grappling with the nature of
      scientific support to substantiate the functional importance of mast cells in
      nonmammalian vertebrates. Ultimately, the origin and evolution of vertebrate mast
      cell is of great interest to comparative immunologists seeking an underlying
      trend in the phylogenetic development of immunity.

PMID- 21875562
TI  - Control of actin assembly by the WH2 domains and their multifunctional tandem
      repeats in Spire and Cordon-Bleu.
AB  - The WASP-homology 2 (WH2) domain is a 5-kDa actin-binding protein module that
      attracts increasing interest by its multifunctional regulation of actin dynamics
      in motile and morphogenetic processes. Identified by a short consensus sequence
      LKKT/V originally found in the actin-sequestering beta-thymosin peptides, the
      betaT/WH2 domains are inserted in a large number of proteins, in particular, the
      WASP proteins involved in cell protrusions. WH2 are found in tandem repeats in
      proteins involved in early development and axis-patterning processes, like Spire
      and Cordon-Bleu. These intrinsically disordered proteins regulate actin assembly
      in an adaptive and versatile fashion by a fine control of local interaction
      dynamics within the WH2-actin complex. Versatility is amplified by the protein
      environment in which the WH2 domain is inserted and by synergy with other
      adjacent actin-binding modules. Multifunctional activities emerge in WH2 repeats,
      including filament nucleation, dramatic severing, and barbed end capping or
      tracking. WH2 domains thus are instrumental in designing customized actin
      regulators.

PMID- 21875563
TI  - Role for primary cilia as flow detectors in the cardiovascular system.
AB  - The cardiovascular system is exposed to biochemical and biomechanical signals.
      Various sensors for these signals have been described and they contribute to
      cardiovascular development, maintenance of vessel integrity during adult life,
      and to pathogenesis. In the past 10years, primary cilia, membrane-covered, rod
      like cellular protrusions, were discovered on multiple cell types of the
      cardiovascular system. Primary cilia are sensory organelles involved in several
      key (developmental) signaling pathways and in chemo- and mechanosensing on a
      myriad of cell types. In the embryonic and adult cardiovascular system, they have
      been demonstrated to function as shear stress sensors on endothelial cells and
      could act as strain sensors on smooth muscle cells and cardiomyocytes and as
      chemosensors on fibroblasts. This review will cover their occurrence and
      elaborate on established and possible functions of primary cilia in the
      cardiovascular system.

PMID- 21875564
TI  - Chemical stress on protein disulfide isomerases and inhibition of their
      functions.
AB  - Protein disulfide isomerase (PDI) is a folding assistant in the endoplasmic
      reticulum (ER) of eukaryotic cells. PDI has multiple roles, acting as a
      chaperone, a binding partner of other proteins, and a hormone reservoir as well
      as a disulfide isomerase in the formation of disulfide bonds. PDI only interacts
      covalently with the cysteines of its substrates, but also binds a variety of
      peptides/proteins and small chemical ligands such as thyroid hormone. Oxidative
      stress and nitrosative stress can cause damage to chaperones, protein misfolding,
      and neurodegenerative disease, by affecting the functional integrity of PDI.
      There are 20 putative PDI-family members in the ER of human cells, but their
      functional differentiation is far from complete. This review discusses recent
      advances in our understanding of the mammalian PDI family of enzymes and focuses
      on their functional properties and interaction with substrates and small chemical
      ligands.

PMID- 21875565
TI  - Retrograde signaling pathway from plastid to nucleus.
AB  - Plastids are a diverse group of organelles found in plants and some parasites.
      Because genes encoding plastid proteins are divided between the nuclear and
      plastid genomes, coordinated expression of genes in two separate genomes is
      indispensable for plastid function. To coordinate nuclear gene expression with
      the functional or metabolic state of plastids, plant cells have acquired a
      retrograde signaling pathway from plastid to nucleus, also known as the plastid
      signaling pathway. To date, several metabolic processes within plastids have been
      shown to affect the expression of nuclear genes. Recent progress in this field
      has also revealed that the plastid signaling pathway interacts and shares common
      components with other intracellular signaling pathways. This review summarizes
      our current knowledge on retrograde signaling from plastid to nucleus in plant
      cells and its role in plant growth and development.

PMID- 21875566
TI  - New insights into the regulation of vascular permeability.
AB  - The endothelium size selectively allows transport of fluids, ions,
      macromolecules, and leukocytes across the vessel wall paracellularly by
      dynamically opening intercellular junctions or transcellularly through caveolae.
      However, persistent opening of intercellular junctions leads to the formation of
      protein-rich edema in the interstitial tissue, a hallmark of tissue inflammation
      that, if left untreated, causes fatal diseases like acute respiratory distress
      syndrome (ARDS). The requirements for continuous transendothelial protein flux
      while limiting leukocyte flux into tissue imply that signaling processes exist in
      the endothelium that dynamically controls protein flux and leukocyte migration
      between the vascular and extravascular spaces. In this chapter, we discuss the
      signaling mechanisms elicited by several well-known inflammatory mediators that
      increase endothelial permeability. Specifically, we have concentrated in
      reviewing the new concepts dealing with the restoration of normal endothelial
      permeability by sphingosine kinase 1 following inflammatory stimulus.

PMID- 21875568
TI  - Sensitization with anti-inflammatory BmAFI of Brugia malayi allows L3 development
      in the hostile peritoneal cavity of Mastomys coucha.
AB  - Filarial parasites survive by inducing tolerance in host but the antigens and
      mechanisms involved are not clear. Recently we found that BmAFI, a Sephadex G-200
      eluted fraction of Brugia malayi adult worm extract, stimulates IL-10 release
      from THP-1 cells. In the present study, we determined the SDS-PAGE profile of
      BmAFI and infective 3rd stage larva (L3), investigated the effect of pre
      sensitization of host with BmAFI on the survival and development of L3 in the non
      permissive peritoneal cavity (p.c.) of the permissive host Mastomys coucha and in
      the p.c. of non-permissive Swiss mice, and studied immunological correlates for
      the observed effects. The parasite development and burden in p.c., was determined
      in sensitized infected M. coucha and Swiss mice and the release of TGF-beta, IL
      4, IL-10, IL-13, IFN-gamma and NO, cellular proliferative response to Con A and
      BmAFI and levels of IgG subclasses and IgE were determined in sensitized infected
      M. coucha. Cellular proliferative response to Con A and BmAFI, mRNA expression of
      GATA-3, CTLA-4 and T-bet were determined in sensitized Swiss mice. In addition,
      the parasitological parameter was also studied in BmAFI-sensitized M. coucha
      exposed to the infection by standard subcutaneous (s.c.) route to assess whether
      sensitization enhances the intensity of infection. BmAFI-sensitization permitted
      survival of L3 and their development to adult stage by day 60 p.i. in the p.c. of
      M. coucha; in non-sensitized animals L3 could molt to L4 only and no parasite
      could be recovered beyond day 30 p.i. In M. coucha that received infection by
      s.c. route, pre-sensitization with BmAFI enhanced the microfilaraemia and adult
      worm recovery. In sensitized Swiss mice L3 could successfully molt to L4 in p.c.
      with improved recovery of parasite. BmAFI sensitization upregulated TGF-beta and
      IL-10 release, IgG1 and IgG2b levels, GATA-3 and CTLA-4 mRNA expression,
      suppressed the cellular proliferative response and downregulated Con A stimulated
      response, IgE, IL-13, IFN-gamma and NO responses. Immunoblot analysis showed that
      the BmAFI antiserum also strongly reacts with some L3 molecules. The results
      show, for the first time, that sensitization with the anti-inflammatory BmAFI
      which shares some of its molecules with those in L3, facilitates parasite
      survival in the non-permissive p.c. of the permissive host M. coucha, render a
      non-permissive Swiss mouse partially permissive to infection and enhances
      parasite load in M. coucha receiving the infection through permissive s.c. route
      by evoking a modified Th2 type of response and anti-inflammatory milieu. In
      conclusion, the findings suggest that the anti-inflammatory BmAFI fraction
      facilitates survival of B. malayi infection even in non-permissive environment.

PMID- 21875567
TI  - DNA vaccination with KMP11 and Lutzomyia longipalpis salivary protein protects
      hamsters against visceral leishmaniasis.
AB  - It was recently shown that immunization of hamsters with DNA plasmids coding
      LJM19, a sand fly salivary protein, partially protected against a challenge with
      Leishmania chagasi, whereas immunization with KMP11 DNA plasmid, a Leishmania
      antigen, induced protection against L. donovani infection. In the present study,
      we evaluated the protective effect of immunization with both LJM19 and KMP11 DNA
      plasmid together. Concerning the protection against an infection by L. chagasi,
      immunization with DNA plasmids coding LJM19 or KMP11, as well as with both
      plasmids combined, induced IFN-gamma production in draining lymph nodes at 7, 14
      and 21 days post-immunization. Immunized hamsters challenged with L. chagasi plus
      Salivary Gland Sonicate (SGS) from Lutzomyia longipalpis showed an enhancement of
      IFN-gamma/IL-10 and IFN-gamma/TGF-beta in draining lymph nodes after 7 and 14
      days of infection. Two and five months after challenge, immunized animals showed
      reduced parasite load in the liver and spleen, as well as increased IFN-gamma/IL
      10 and IFN-gamma/TGF-beta ratios in the spleen. Furthermore, immunized animals
      remained with a normal hematological profile even five months after the
      challenge, whereas L. chagasi in unimmunized hamsters lead to a significant
      anemia. The protection observed with LJM19 or KMP11 DNA plasmids used alone was
      very similar to the protection obtained by the combination of both plasmids.

PMID- 21875569
TI  - Human cystic echinococcosis in South Africa.
AB  - Cystic echinococcosis is recognised as causing considerable morbidity and even
      mortality in South Africa, but the epidemiology of the disease is to date
      unknown. From current evidence there are also concerns that co-infections with
      HIV and tuberculosis (TB) considerably increase CE-associated morbidity. The aim
      of this analysis was to characterise clinical features and disease burden of CE
      in South Africa in preparation for a prospective study. Retrospective case note
      analysis of patients presenting to two large academic hospitals in Johannesburg,
      South Africa, for clinical and demographic data was performed. In addition, data
      of the National Health Laboratory Service were accessed for requested serological
      and microscopic investigations for CE and the numbers of positive results
      evaluated. According to a recently published definition, 14 cases of confirmed CE
      and 9 cases of probable CE were identified at both hospitals. When accessing the
      national database it became apparent that even with the most conservative
      estimate at least 137 patients per year present with CE in South Africa. However,
      numbers are likely to be much higher for a variety of reasons. Further
      prospective analysis is necessary to shed more light on the epidemiology,
      clinical presentation and risk factors for CE, which is currently underway.

PMID- 21875570
TI  - Amyloid formation using 1-butyl-3-methyl-imidazolium-based ionic liquids.
AB  - Amyloid fibrils are highly organized protein filaments that can be used as novel
      biomaterials. In this study, we show that proteins could be selectively induced
      to form amyloid fibrils at room temperature by the introduction of imidazolium
      salts, which could trigger the self-assembly process with their hydrophobic and
      ionic properties.

PMID- 21875571
TI  - Targeting CD9 produces stimulus-independent antiangiogenic effects predominantly
      in activated endothelial cells during angiogenesis: a novel antiangiogenic
      therapy.
AB  - The precise roles of tetraspanin CD9 are unclear. Here we show that CD9 plays a
      stimulus-independent role in angiogenesis and that inhibiting CD9 expression or
      function is a potential antiangiogenic therapy. Knocking down CD9 expression
      significantly inhibited in vitro endothelial cell migration and invasion induced
      by vascular endothelial growth factor (VEGF) or hepatocyte growth factor (HGF).
      Injecting CD9-specific small interfering RNA (siRNA-CD9) markedly inhibited HGF-
      or VEGF-induced subconjunctival angiogenesis in vivo. Both results revealed
      potent and stimulus-independent antiangiogenic effects of targeting CD9.
      Furthermore, intravitreous injections of siRNA-CD9 or anti-CD9 antibodies were
      therapeutically effective for laser-induced retinal and choroidal
      neovascularization in mice, a representative ocular angiogenic disease model. In
      terms of the mechanism, growth factor receptor and downstream signaling
      activation were not affected, whereas abnormal localization of integrins and
      membrane type-1 matrix metalloproteinase was observed during angiogenesis, by
      knocking down CD9 expression. Notably, knocking down CD9 expression did not
      induce death and mildly inhibited proliferation of quiescent endothelial cells
      under conditions without an angiogenic stimulus. Thus, CD9 does not directly
      affect growth factor-induced signal transduction, which is required in
      angiogenesis and normal vasculature, but is part of the angiogenesis machinery in
      endothelial cells during angiogenesis. In conclusion, targeting CD9 produced
      stimulus-independent antiangiogenic effects predominantly in activated
      endothelial cells during angiogenesis, and appears to be an effective and safe
      antiangiogenic approach. These results shed light on the biological roles of CD9
      and may lead to novel antiangiogenic therapies.

PMID- 21875572
TI  - Activation of non-canonical Wnt/JNK pathway by Wnt3a is associated with
      differentiation fate determination of human bone marrow stromal (mesenchymal)
      stem cells.
AB  - The canonical Wnt signaling pathway can determine human bone marrow stromal
      (mesenchymal) stem cell (hMSC) differentiation fate into osteoblast or adipocyte
      lineages. However, its downstream targets in MSC are not well characterized.
      Thus, using DNA microarrays, we compared global gene expression patterns induced
      by Wnt3a treatment in two hMSC lines: hMSC-LRP5(T253) and hMSC-LRP5(T244) cells
      carrying known mutations of Wnt co-receptor LRP5 (T253I or T244M) that either
      enhances or represses canonical Wnt signaling, respectively. Wnt3a treatment of
      hMSC activated not only canonical Wnt signaling, but also the non-canonical
      Wnt/JNK pathway through upregulation of several non-canonical Wnt components e.g.
      naked cuticle 1 homolog (NKD1) and WNT11. Activation of the non-canonical Wnt/JNK
      pathway by anisomycin enhanced osteoblast differentiation whereas its inhibition
      by SP600125 enhanced adipocyte differentiation of hMSC. In conclusion, canonical
      and non-canonical Wnt signaling cooperate in determining MSC differentiation
      fate.

PMID- 21875573
TI  - Delayed cell cycle progression from SEPW1 depletion is p53- and p21-dependent in
      MCF-7 breast cancer cells.
AB  - Selenium (Se) is an essential redox-active trace element with close connections
      to cancer. Most of Se's biological functions have been attributed to the
      antioxidant properties of Se-containing proteins. However, the relative
      contribution of selenoproteins and small Se compounds in cancer protection is
      still a matter of debate. The tumor suppressor p53 is the most frequently mutated
      gene in human cancer and is often referred to as the "guardian of the genome". In
      response to genomic stresses, p53 causes cell cycle arrest to allow time for
      genomic damage to be repaired before cell division or induces apoptosis to
      eliminate irreparably damaged cells. Selenoprotein W (SEPW1) is a highly
      conserved small thioredoxin-like protein required for cell cycle progression. The
      present work shows that SEPW1 facilitates the G1 to S-phase transition by down
      regulating expression of the cyclin-dependent kinase inhibitor p21. SEPW1
      controls p21 by modulating levels of the p53 transcription factor, and this is
      associated with changes in phosphorylation of Ser-33 in p53. More work is needed
      to identify the mechanism by which SEPW1 regulates phosphorylation of Ser-33 and
      the kinase or phosphatase enzymes involved.

PMID- 21875574
TI  - Co-expression of interleukin 12 enhances antitumor effects of a novel chimeric
      promoter-mediated suicide gene therapy in an immunocompetent mouse model.
AB  - The human telomerase reverse transcriptase (hTERT) promoter has been widely used
      in target gene therapy of cancer. However, low transcriptional activity limited
      its clinical application. Here, we designed a novel dual radiation-inducible and
      tumor-specific promoter system consisting of CArG elements and the hTERT
      promoter, resulting in increased expression of reporter genes after gamma
      irradiation. Therapeutic and side effects of adenovirus-mediated horseradish
      peroxidase (HRP)/indole-3-acetic (IAA) system downstream of the chimeric promoter
      were evaluated in mice bearing Lewis lung carcinoma, combining with or without
      adenovirus-mediated interleukin 12 (IL12) gene driven by the cytomegalovirus
      promoter. The combination treatment showed more effective suppression of tumor
      growth than those with single agent alone, being associated with pronounced
      intratumoral T-lymphocyte infiltration and minor side effects. Our results
      suggest that the combination treatment with HRP/IAA system driven by the novel
      chimeric promoter and the co-expression of IL12 might be an effective and safe
      target gene therapy strategy of cancer.

PMID- 21875575
TI  - A probabilistic approach to microRNA-target binding.
AB  - Elucidation of microRNA activity is a crucial step in understanding gene
      regulation. One key problem in this effort is how to model the pairwise
      interactions of microRNAs with their targets. As this interaction is strongly
      mediated by their sequences, it is desired to set-up a probabilistic model to
      explain the binding preferences between a microRNA sequence and the sequence of a
      putative target. To this end, we introduce a new model of microRNA-target
      binding, which transforms an aligned duplex to a new sequence and defines the
      likelihood of this sequence using a Variable Length Markov Chain. It offers a
      complementary representation of microRNA-mRNA pairs for microRNA target
      prediction tools or other probabilistic frameworks of integrative gene regulation
      analysis. The performance of present model is evaluated by its ability to predict
      microRNA-target mRNA interaction given a mature microRNA sequence and a putative
      mRNA binding site. In regard to classification accuracy, it outperforms two
      recent methods based on thermodynamic stability and sequence complementarity. The
      experiments can also unveil the effects of base pairing types and non-seed region
      in duplex formation.

PMID- 21875576
TI  - Nitrative and oxidative DNA damage caused by K-ras mutation in mice.
AB  - Ras mutation is important for carcinogenesis. Carcinogenesis consists of multi
      step process with mutations in several genes. We investigated the role of DNA
      damage in carcinogenesis initiated by K-ras mutation, using conditional
      transgenic mice. Immunohistochemical analysis revealed that mutagenic 8
      nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) were apparently
      formed in adenocarcinoma caused by mutated K-ras. 8-Nitroguanine was co-localized
      with iNOS, eNOS, NF-kappaB, IKK, MAPK, MEK, and mutated K-ras, suggesting that
      oncogenic K-ras causes additional DNA damage via signaling pathway involving
      these molecules. It is noteworthy that K-ras mutation mediates not only cell over
      proliferation but also the accumulation of mutagenic DNA lesions, leading to
      carcinogenesis.

PMID- 21875577
TI  - Optical observation of cell sonoporation with low intensity ultrasound.
AB  - Sonoporation is a promising drug delivery technique with great potential in
      medicine. However, its applications have been limited mostly by the lack of
      understanding its underlying biophysical mechanism, partly due to the inadequacy
      of the existing models for coupling with highly sensitive imaging techniques to
      directly observe the actual precursor events of cell-microbubble interaction
      under low intensity ultrasound. Here, we introduce a new in vitro method
      utilizing capillary-microgripping system and micro-transducer to achieve maximum
      level of experimental flexibility for capturing real time highly magnified images
      of cell-microbubble interaction, hitherto unseen in this context. Insonation of
      isolated single cells and microbubbles parallel with high speed microphotography
      and fluorescence microscopy allowed us to identify dynamic responses of cell
      membrane/microbubble in correlation with sonoporation. Our results showed that
      bubble motion and linear oscillation in close contact with the cell membrane can
      cause local deformation and transient porosity in the cell membrane without
      rupturing it. This method can also be used as an in situ gene/drug delivery
      system of targeted cells for non-invasive clinical applications.

PMID- 21875578
TI  - Tigutcystatin, a cysteine protease inhibitor from Triatoma infestans midgut
      expressed in response to Trypanosoma cruzi.
AB  - The insect Triatoma infestans is a vector of Trypanosoma cruzi, the etiological
      agent of Chagas disease. A cDNA library was constructed from T. infestans
      anterior midgut, and 244 clones were sequenced. Among the EST sequences, an open
      reading frame (ORF) with homology to a cystatin type 2 precursor was identified.
      Then, a 288-bp cDNA fragment encoding mature cystatin (lacking signal peptide)
      named Tigutcystatin was cloned fused to a N-terminal His tag in pET-14b vector,
      and the protein expressed in Escherichia coli strain Rosetta gami. Tigutcystatin
      purified and cleaved by thrombin to remove His tag presented molecular mass of 11
      kDa and 10,137 Da by SDS-PAGE and MALDI-TOF mass spectrometry, respectively.
      Purified Tigutcystatin was shown to be a tight inhibitor towards cruzain, a T.
      cruzi cathepsin L-like enzyme (K(i)=3.29 nM) and human cathepsin L (K(i)=3.78
      nM). Tissue specific expression analysis showed that Tigutcystatin was mostly
      expressed in anterior midgut, although amplification in small intestine was also
      detected by semi quantitative RT-PCR. qReal time PCR confirmed that Tigutcystatin
      mRNA is significantly up-regulated in anterior midgut when T. infestans is
      infected with T. cruzi. Together, these results indicate that Tigutcystatin may
      be involved in modulation of T. cruzi in intestinal tract by inhibiting parasite
      cysteine proteases, which represent the virulence factors of this protozoan.

PMID- 21875579
TI  - The transcription factor FOXM1c is activated by protein kinase CK2, protein
      kinase A (PKA), c-Src and Raf-1.
AB  - The transcription factor FOXM1c possesses a very strong C-terminal TAD
      (transactivation domain), but full-length FOXM1c is only a weak transactivator
      because the TAD is completely inhibited by the auto-inhibitory N-terminus. The N
      terminus blocks the TAD by directly binding to the TAD. Accordingly, FOXM1c
      deletion mutants without N-terminus are strong transactivators. Therefore, the
      question arises whether signals exist, which activate full-length FOXM1c by
      releasing the FOXM1c-TAD from its inhibition by the N-terminus. Indeed, full
      length FOXM1c is strongly activated by protein kinase CK2 and PKA (protein kinase
      A). Both CK2 and PKA do not activate a FOXM1c deletion mutant without N-terminus
      demonstrating that the activation of FOXM1c by CK2 and PKA depends on the
      presence of the N-terminus. Consequently, CK2 and PKA activate FOXM1c by
      alleviating the inhibition of FOXM1c by its N-terminus. The presence of two
      potential CK2 phosphorylation sites and two potential PKA phosphorylation sites
      in the N-terminus of FOXM1c suggests that CK2 and PKA may activate FOXM1c through
      phosphorylation of the FOXM1c N-terminus. Thus, CK2 and PKA strongly activate
      full-length FOXM1c because they alleviate the repression of FOXM1c by its own
      auto-inhibitory N-terminus. Also c-Src activates full-length FOXM1c by relieving
      the inhibition of FOXM1c by its N-terminus. In contrast, Raf-1 activates FOXM1c
      independently of the FOXM1c N-terminus. In summary, this study shows for the
      first time that FOXM1c is activated by the four kinases CK2, PKA, c-Src and Raf
      1.

PMID- 21875580
TI  - Ginsenoside metabolite compound K differentially antagonizing tumor necrosis
      factor-alpha-induced monocyte-endothelial trafficking.
AB  - Human leukocyte endothelial adhesion and transmigration occur in the early stage
      of the pathogenesis of atherosclerosis. Vascular endothelial cells are targeted
      by pro-inflammatory cytokines modulating many gene proteins responsible for cell
      adhesion, thrombosis and inflammatory responses. This study examined the
      potential of compound K to inhibit the pro-inflammatory cytokine TNF-alpha
      induction of monocyte adhesion onto TNF-alpha-activated human umbilical vein
      endothelial cells (HUVEC). HUVEC were cultured with 10ng/ml TNF-alpha with
      individual ginsenosides of Rb1, Rc, Re, Rh1 and compound K (CK). Ginsenosides at
      doses of ?50MUM did not show any cytotoxicity. TNF-alpha induced THP-1 monocyte
      adhesion to HUVEC, and such induction was attenuated by Rh1 and CK. Consistently,
      CK suppressed TNF-alpha-induced expression of HUVEC adhesion molecules of VCAM-1,
      ICAM-1 and E-selectin, and also Rh1 showed a substantial inhibition. Rh1 and CK
      dampened induction of counter-receptors, alpha4/beta1 integrin VLA-4 and
      alphaL/beta2 integrin LFA-1 in TNF-alpha-treated THP-1 cells. Additionally, CK
      diminished THP-1 secretion of MMP-9 required during transmigration, inhibiting
      transendothelial migration of THP-1 cells. CK blunted TNF-alpha-promoted IL-8
      secretion of HUVEC and CXCR1 expression of THP-1 monocytes. Furthermore, TNF
      alpha-activated endothelial IkappaB phosphorylation and NF-kappaB nuclear
      translocation were disturbed by CK, and TNF-alpha induction of alpha4/beta1
      integrin was abrogated by the NF-kappaB inhibitor SN50. These results demonstrate
      that CK exerts anti-atherogenic activity with blocking leukocyte endothelial
      interaction and transmigration through negatively mediating NF-kappaB signaling.

PMID- 21875581
TI  - Immune modulation and modulators in Heligmosomoides polygyrus infection.
AB  - The intestinal nematode parasite Heligmosomoides polygyrus bakeri exerts
      widespread immunomodulatory effects on both the innate and adaptive immune system
      of the host. Infected mice adopt an immunoregulated phenotype, with abated
      allergic and autoimmune reactions. At the cellular level, infection is
      accompanied by expanded regulatory T cell populations, skewed dendritic cell and
      macrophage phenotypes, B cell hyperstimulation and multiple localised changes
      within the intestinal environment. In most mouse strains, these act to block
      protective Th2 immunity. The molecular basis of parasite interactions with the
      host immune system centres upon secreted products termed HES (H. polygyrus
      excretory-secretory antigen), which include a TGF-beta-like ligand that induces
      de novo regulatory T cells, factors that modify innate inflammatory responses,
      and molecules that block allergy in vivo. Proteomic and transcriptomic definition
      of parasite proteins, combined with biochemical identification of immunogenic
      molecules in resistant mice, will provide new candidate immunomodulators and
      vaccine antigens for future research.

PMID- 21875582
TI  - The internal transcribed spacer 1 (ITS-1), a controversial marker for the genetic
      diversity of Trypanosoma evansi.
AB  - Seven Trypanosoma evansi isolates from China and a Trypanosoma congolense sp.
      gifted from Kenya were characterized genetically by the internal transcribed
      spacer 1 (ITS-1) of nuclear ribosomal DNA (rDNA). The ITS-1 rDNA with the length
      of 338-342 bp was amplified by polymerase chain reaction (PCR) and sequenced from
      individual isolates of T. evansi. Although sequence variation between T. evansi
      isolates from China only was 0.3-3.8%, the constructed phylogenetic tree based on
      the ITS-1 rDNA sequence by the method of neighbor-joining and maximum parsimony
      revealed the genetic diversity among T. evansi isolates from China. For T.
      congolense sp., the most phylogenetically related species was T. congolense
      IL1180. Although the sequence variation ranged 0.8-14.5% between T. congolense
      isolates, the phylogenetic tree can not reflected the genetic diversity among T.
      congolense isolates perhaps because of the fewer number of isolates and
      sequences. The data could be applicable for the survey of parasite dynamics,
      epidemiological studies as well as prevention and control of the disease.

PMID- 21875583
TI  - Th17 responses in Echinostoma caproni infections in hosts of high and low
      compatibility.
AB  - In order to investigate the factors determining the expulsion of intestinal
      helminths, we have analyzed the in vivo expression of IL-17, TGF-beta and IL-23
      in several tissues of two host species displaying different compatibility with
      Echinostoma caproni (Trematoda). We did not observe upregulation of these
      cytokines in any of the tissues of the high compatible host (mice). In contrast,
      the responses in the host of low compatibility (rats) with the parasite were
      markedly different. Significant increases in the expression of IL-17 and TGF-beta
      were observed in the Peyer's patches and the intestine from the 2 to 8 weeks post
      infection. The expression of IL-23 was upregulated from 2 to 4 weeks post
      infection in the spleen, Peyer's patches and the intestine. Considering together
      our results with those published previously the development of chronic infections
      appears to be related with the development of local Th1 responses, whereas the
      early rejection of the worms is mediated by the development a biased Th17/Th2
      phenotype. The Th17 response generated in rats may facilitate the worm expulsion
      via the suppression of the inflammatory Th1 responses and the increase in
      intestinal contractility.

PMID- 21875584
TI  - The structure of helix 89 of 23S rRNA is important for peptidyl transferase
      function of Escherichia coli ribosome.
AB  - Helix 89 of the 23S rRNA connects ribosomal peptidyltransferase center and
      elongation factor binding site. Secondary structure of helix 89 determined by X
      ray structural analysis involves less base pairs then could be drawn for the
      helix of the same primary structure. It can be that alternative secondary
      structure might be realized at some stage of translation. Here by means of site
      directed mutagenesis we stabilized either the "X-ray" structure or the structure
      with largest number of paired nucleotides. Mutation UU2492-3C which aimed to
      provide maximal pairing of the helix 89 of the 23S rRNA was lethal. Mutant
      ribosomes were unable to catalyze peptide transfer independently either with
      aminoacyl-tRNA or puromycin.

PMID- 21875586
TI  - A view to natural killer cells in hepatitis C.

PMID- 21875587
TI  - Phenotypic switching in diabetic gastroparesis: mechanism directs therapy.

PMID- 21875585
TI  - Dissecting the diverse functions of the metastasis suppressor CD82/KAI1.
AB  - The recent identification of metastasis suppressor genes, the products of which
      inhibit metastasis but not primary tumor growth, distinguishes oncogenic
      transformation and tumor suppression from a hallmark of malignancy, the ability
      of cancer cells to invade sites distant from the primary tumor. The metastasis
      suppressor CD82/KAI1 is a member of the tetraspanin superfamily of glycoproteins.
      CD82 suppresses metastasis by multiple mechanisms including inhibition of cell
      motility and invasion, promotion of cell polarity as well as induction of
      senescence and apoptosis in response to extracellular stimuli. A common feature
      of these diverse effects is CD82 regulation of membrane organization as well as
      protein trafficking and interactions, which affects cellular signaling and
      intercellular communication.

PMID- 21875588
TI  - The ductal plate: a source of progenitors and hepatocytes in the adult liver.

PMID- 21875590
TI  - Folic acid alleviates oxidative stress and hyperhomocysteinemia involved in
      testicular dysfunction of hypothyroid rats.
AB  - Although there is general agreement that thyroid hormone is an important hormonal
      regulator of testis physiology during development period, its role in the post
      pubertal and adult testes is still controversial. Furthermore, most experimental
      studies to date have focused on thyroid hormone effects on the developing testes
      and only limited data are available on its role in spermatogenesis. This study
      evaluated some biochemical alterations in post-pubertal hypothyroidism and its
      impact on testicular function. Additionally, the ameliorating role of folic acid
      supplementation was investigated. Fifty male albino rats were randomly divided
      into five groups (group I, control; group II, folic acid; group III, 0.05%
      propylthiouracil-induced hypothyroid rats; group IV, co-treatment; group V, post
      treatment). Plasma total homocysteine, total NO metabolites, malondialdehyde and
      GSSG/GSH ratio quantified by HPLC significantly (P<0.05) increased in hypothyroid
      rats as compared to controls. These biochemical alterations at least in part
      disrupted spermatogenesis in these experimental models. Folic acid supplemented
      after restoration of the euthyroid state (group V) presented better amelioration
      to spermatogenesis over its concurrent supplementation (group IV). This
      postulates an indirect negative impact of post-pubertal hypothyroidism on
      testicular function through development of these alterations. This is plus the
      observed role of folic acid supplementation in enhancing spermatogenesis,
      boosting sperm concentration and building up the antioxidant status against the
      oxidants in the present study. If confirmed in human beings, our results could
      propose that folic acid can be used as an adjuvant therapy in hypothyroidism
      disorders with thyroxin replacement therapy.

PMID- 21875591
TI  - Crustacean cardioactive peptide in the Chagas' disease vector, Rhodnius prolixus:
      presence, distribution and physiological effects.
AB  - Crustacean cardioactive peptide (CCAP), a cyclic nonapeptide (PFCNAFTGCamide),
      has multifunctional roles in insects including stimulating visceral and cardiac
      muscle contraction, and regulating ecdysis. Previously, we have sequenced the
      cDNA for CCAP from Rhodnius prolixus central nervous system (CNS) and shown
      expression of the CCAP transcript in neurons of the CNS. In the present study, we
      have biochemically identified and sequenced CCAP from 5th instar R. prolixus CNS
      using matrix-assisted laser desorption ionization-time of flight-tandem mass
      spectrometry, and mapped CCAP-like immunoreactivity in the CNS and peripheral
      tissues of 5th instar R. prolixus. Physiologically, the hindgut of R. prolixus
      was found to be sensitive to CCAP, showing dose-dependent increases in
      contractions with threshold at 5 * 10(-9) M and maximum response at 10(-7) M
      CCAP. Also, CCAP was found to increase the frequency of the heartbeat in a
      reversible, dose-dependent manner, with threshold close to 10(-11) M and maximum
      response at 10(-10) M CCAP.

PMID- 21875592
TI  - Lipophorin acts as a shuttle of lipids to the milk gland during tsetse fly
      pregnancy.
AB  - During pregnancy in the viviparous tsetse fly, lipid mobilization is essential
      for the production of milk to feed the developing intrauterine larva. Lipophorin
      (Lp) functions as the major lipid transport protein in insects and closely
      related arthropods. In this study, we assessed the role of Lp and the lipophorin
      receptor (LpR) in the lipid mobilization process during tsetse reproduction. We
      identified single gene sequences for GmmLp and GmmLpR from the genome of
      Glossinamorsitansmorsitans, and measured spatial and temporal expression of gmmlp
      and gmmlpr during the female reproductive cycle. Our results show that expression
      of gmmlp is specific to the adult fat body and larvae. In the adult female, gmmlp
      expression is constitutive. However transcript levels increase in the larva as it
      matures within the mother's uterus, reaching peak expression just prior to
      parturition. GmmLp was detected in the hemolymph of pregnant females and larvae,
      but not in the uterine fluid or larval gut contents ruling out the possibility of
      direct transfer of GmmLp from mother to offspring. Transcripts for gmmlpr were
      detected in the head, ovaries, midgut, milk gland/fat body, ovaries and
      developing larva. Levels of gmmlpr remain stable throughout the first and second
      gonotrophic cycles with a slight dip observed during the first gonotrophic cycle.
      GmmLpR was detected in multiple tissues, including the midgut, fat body, milk
      gland, spermatheca and head. Knockdown of gmmlp by RNA interference resulted in
      reduced hemolymph lipid levels, delayed oocyte development and extended larval
      gestation. Similar suppresion of gmmlpr did not significantly reduce hemolymph
      lipid levels or oogenesis duration, but did extend the duration of larval
      development. Thus, GmmLp function as the primary shuttle for lipids originating
      from the midgut and fat body to the ovaries and milk gland to supply resources
      for developing oocytes and larval nourishment, respectively. Once in the milk
      gland however, lipids are apparently transferred into the developing larva not by
      lipophorin but by another carrier lipoprotein.

PMID- 21875593
TI  - ESCRT machinery potentiates HIV-1 utilization of the PI(4,5)P(2)-PLC-IP3R-Ca(2+)
      signaling cascade.
AB  - Human immunodeficiency virus type 1 (HIV-1) release efficiency is directed by
      late (L) domain motifs in the viral structural precursor polyprotein Gag, which
      serve as links to the ESCRT (endosomal sorting complex required for transport)
      machinery. Linkage is normally through binding of Tsg101, an ESCRT-1 component,
      to the P(7)TAP motif in the p6 region of Gag. In its absence, budding is directed
      by binding of Alix, an ESCRT adaptor protein, to the LY(36)PX(n)L motif in Gag.
      We recently showed that budding requires activation of the inositol 1,4,5
      triphosphate receptor (IP3R), a protein that "gates" Ca(2+) release from
      intracellular stores, triggers Ca(2+) cell influx and thereby functions as a
      major regulator of Ca(2+) signaling. In the present study, we determined whether
      the L domain links Gag to Ca(2+) signaling machinery. Depletion of IP3R and
      inactivation of phospholipase C (PLC) inhibited budding whether or not Tsg101 was
      bound to Gag. PLC hydrolysis of phosphatidylinositol-(4,5)-bisphosphate generates
      inositol (1,4,5)-triphosphate, the ligand that activates IP3R. However, with
      Tsg101 bound, Gag release was independent of Gq-mediated activation of PLC, and
      budding was readily enhanced by pharmacological stimulation of PLC. Moreover,
      IP3R was redistributed to the cell periphery and cytosolic Ca(2+) was elevated,
      events indicative of induction of Ca(2+) signaling. The results suggest that L
      domain function, ESCRT machinery and Ca(2+) signaling are linked events in Gag
      release.

PMID- 21875594
TI  - Light-induced conformational changes in full-length Arabidopsis thaliana
      cryptochrome.
AB  - Cryptochromes (CRYs) are widespread flavoproteins with homology to photolyases
      (PHRs), a class of blue-light-activated DNA repair enzymes. Unlike PHRs, both
      plant and animal CRYs have a C-terminal domain. This cryptochrome C-terminal
      (CCT) domain mediates interactions with other proteins, while the PHR-like domain
      converts light energy into a signal via reduction and radical formation of the
      flavin adenine dinucleotide cofactor. However, the mechanism by which the PHR
      like domain regulates the CCT domain is not known. Here, we applied the pulsed
      laser-induced transient grating method to detect conformational changes induced
      by blue-light excitation of full-length Arabidopsis thaliana cryptochrome 1
      (AtCRY1). A significant reduction in the diffusion coefficient of AtCRY1 was
      observed upon photoexcitation, indicating that a large conformational change
      occurs in this monomeric protein. AtCRY1 containing a single mutation (W324F)
      that abolishes an intra-protein electron transfer cascade did not exhibit this
      conformational change. Moreover, the conformational change was much reduced in
      protein lacking the CCT domain. Thus, we conclude that the observed large
      conformational changes triggered by light excitation of the PHR-like domain
      result from C-terminal domain rearrangement. This inter-domain modulation would
      be critical for CRYs' ability to transduce a blue-light signal into altered
      protein-protein interactions for biological activity. Lastly, we demonstrate that
      the transient grating technique provides a powerful method for the direct
      observation and understanding of photoreceptor dynamics.

PMID- 21875595
TI  - Characterization of a myosin VII MyTH/FERM domain.
AB  - A group of closely related myosins is characterized by the presence of at least
      one MyTH/FERM (myosin tail homology; band 4.1, ezrin, radixin, moesin) domain in
      their C-terminal tails. This domain interacts with a variety of binding partners,
      and mutations in either the MyTH4 or the FERM domain of myosin VII and myosin XV
      result in deafness, highlighting the functional importance of each domain. The N
      terminal MyTH/FERM region of Dictyostelium myosin VII (M7) has been isolated as a
      first step toward gaining insight into the function of this domain and its
      interaction with binding partners. The M7 MyTH4/FERM domain (MF1) binds to both
      actin and microtubules in vitro, with dissociation constants of 13.7 and 1.7 MUM,
      respectively. Gel filtration and UV spectroscopy reveal that MF1 exists as a
      monomer in solution and forms a well-folded, compact conformation with a high
      degree of secondary structure. These results indicate that MF1 forms an
      integrated structural domain that serves to couple actin filaments and
      microtubules in specific regions of the cytoskeleton.

PMID- 21875596
TI  - Role of interaction of XPF with RPA in nucleotide excision repair.
AB  - Nucleotide excision repair (NER) is a very important defense system against
      various types of DNA damage, and it is necessary for maintaining genomic
      stability. The molecular mechanism of NER has been studied in considerable
      detail, and it has been shown that proper protein-protein interactions among NER
      factors are critical for efficient repair. A structure-specific endonuclease, XPF
      ERCC1, which makes the 5' incision in NER, was shown to interact with a single
      stranded DNA binding protein, RPA. However, the biological significance of this
      interaction was not studied in detail. We used the yeast two-hybrid assay to
      determine that XPF interacts with the p70 subunit of RPA. To further examine the
      role of this XPF-p70 interaction, we isolated a p70-interaction-deficient mutant
      form of XPF that contains a single amino acid substitution in the N-terminus of
      XPF by the reverse yeast two-hybrid assay using randomly mutagenized XPF. The
      biochemical properties of this RPA-interaction-deficient mutant XPF-ERCC1 are
      very similar to those of wild-type XPF-ERCC1 in vitro. Interestingly, expression
      of this mutated form of XPF in the XPF-deficient Chinese hamster ovary cell line,
      UV41, only partially restores NER activity and UV resistance in vivo compared to
      wild-type XPF. We discovered that the RPA-interaction-deficient XPF is not
      localized in nuclei and the mislocalization of XPF-ERCC1 prevents the complex
      from functioning in NER.

PMID- 21875598
TI  - Complete modification maps for the cytosolic small and large subunit rRNAs of
      Euglena gracilis: functional and evolutionary implications of contrasting
      patterns between the two rRNA components.
AB  - In the protist Euglena gracilis, the cytosolic small subunit (SSU) rRNA is a
      single, covalently continuous species typical of most eukaryotes; in contrast,
      the large subunit (LSU) rRNA is naturally fragmented, comprising 14 separate RNA
      molecules instead of the bipartite (28S+5.8S) eukaryotic LSU rRNA typically seen.
      We present extensively revised secondary structure models of the E. gracilis SSU
      and LSU rRNAs and have mapped the positions of all of the modified nucleosides in
      these rRNAs (88 in SSU rRNA and 262 in LSU rRNA, with only 3 LSU rRNA
      modifications incompletely characterized). The relative proportions of ribose
      methylated nucleosides and pseudouridine (~60% and ~35%, respectively) are
      closely similar in the two rRNAs; however, whereas the Euglena SSU rRNA has about
      the same absolute number of modifications as its human counterpart, the Euglena
      LSU rRNA has twice as many modifications as the corresponding human LSU rRNA. The
      increased levels of rRNA fragmentation and modification in E. gracilis LSU rRNA
      are correlated with a 3-fold increase in the level of mispairing in helical
      regions compared to the human LSU rRNA. In contrast, no comparable increase in
      mispairing is seen in helical regions of the SSU rRNA compared to its homologs in
      other eukaryotes. In view of the reported effects of both ribose-methylated
      nucleoside and pseudouridine residues on RNA structure, these correlations lead
      us to suggest that increased modification in the LSU rRNA may play a role in
      stabilizing a 'looser' structure promoted by elevated helical mispairing and a
      high degree of fragmentation.

PMID- 21875597
TI  - The interaction of cofilin with the actin filament.
AB  - Cofilin is a key actin-binding protein that is critical for controlling the
      assembly of actin within the cell. Here, we present the results of molecular
      docking and dynamics studies using a muscle actin filament and human cofilin I.
      Guided by extensive mutagenesis results and other biophysical and structural
      studies, we arrive at a model for cofilin bound to the actin filament. This
      predicted structure agrees very well with electron microscopy results for cofilin
      decorated filaments, provides molecular insight into how the known F- and G-actin
      sites on cofilin interact with the filament, and also suggests new interaction
      sites that may play a role in cofilin binding. The resulting atomic-scale model
      also helps us understand the molecular function and regulation of cofilin and
      provides testable data for future experimental and simulation work.

PMID- 21875599
TI  - RNA interference as a tool for exploring HIV-1 robustness.
AB  - Short interfering RNAs (siRNAs) that target viral genes can efficiently inhibit
      human immunodeficiency virus type 1 (HIV-1) replication. Nevertheless, there is
      the potential for viral escape, particularly with a highly mutable target such as
      HIV-1. We present a novel strategy for anticipating and preventing viral escape
      using second-generation siRNAs. The evolutionary capacity of HIV-1 was tested by
      exerting strong selective pressure on a highly conserved sequence in the HIV-1
      genome. We assayed the antiviral efficacy of five overlapping siRNAs directed
      against an essential region of the HIV-1 protease. Serial viral transfers in U87
      CD4-CXCR4 cells were performed using four of the siRNAs. This procedure was
      repeated until virus breakthrough was detected. After several serial culture
      passages, resistant virus with a single point mutation in the targeted region was
      detected in the culture supernatants. The emergence of resistant virus was
      confirmed by molecular cloning and DNA sequencing of viral RNA. The most common
      escape route was the D30N mutation. Importantly, the addition of a second
      generation siRNA that matched the D30N mutation restored viral inhibition and
      delayed development of escape variants. Passages performed with both siRNAs
      prevented the emergence of the D30N escape mutant and forced the virus to develop
      new escape routes. Thus, second-generation siRNAs can be used to block escape
      from RNA interference (RNAi) and to search for new RNAi escape routes. The
      protocol described here may be useful for exploring the sequence space available
      for HIV-1 evolution and for producing attenuated or deleterious viruses.

PMID- 21875600
TI  - Savanna domain in the herbivores-fire parameter space exploiting a tree-grass
      soil water dynamic model.
AB  - The tree-grass co-existence in savannas involves multiple and sometimes connected
      biogeophysical conditions. The savanna domain, its boundaries, and transitions
      (gradual or abrupt) to other vegetation types (i.e., grassland or forest) are
      fundamental for the management of ecosystems and for preserving the biodiversity
      in present conditions and in future changing scenarios. Here we investigate the
      savanna domain within grazers-fire and browsers-fire parameter planes through a
      simple ecohydrological model of tree-grass-soil water dynamics. Stability maps
      allow to identify savanna domains and to show the behavior of vegetation under
      increasing pressure of grazing and browsing. Stability maps shed light on the
      causes behind possible vegetation abrupt transitions (e.g., forest collapse and
      bush encroachment). An application to 15 African savannas sites is presented and
      discussed with the support of a local sensitivity analysis of the model's
      parameters.

PMID- 21875601
TI  - The filling law: a general framework for leaf folding and its consequences on
      leaf shape diversity.
AB  - Leaves are packed in a bud in different ways, being flat, rolled, or folded, but
      always filling the whole bud volume. This "filling law" has many consequences, in
      particular on the shapes of growing folded leaves. This is shown here for
      different types of folding and packing. The folded volume is roughly a part of an
      ellipsoid, with the veins on the outside rounded face and the lamina margin on
      the adaxial plane. The veins on the abaxial side protect the fragile lamina
      inside. The first general consequence of the folds and the space limitation of
      the lamina growth is the presence of symmetries on the leaf shape, and the second
      is the quantitative relationships between the sizes of the lobes and sinuses. For
      particular geometries, the leaf lamina can be limited by lateral veins, creating
      spoon-like lobes, or tangent cuts, creating asymmetrical wavy perimeters. Changes
      in the packing between different cultivars correspond to changes in the mature
      leaf shapes. Each particular case shows how pervasive the geometrical
      consequences of the filling law are.

PMID- 21875602
TI  - New modeling approach for bounding flight in birds.
AB  - A new modeling approach is presented which accounts for the unsteady motion
      features and dynamics characteristics of bounding flight. For this purpose, a
      realistic mathematical model is developed to describe the flight dynamics of a
      bird with regard to a motion which comprises flapping and bound phases involving
      acceleration and deceleration as well as, simultaneously, pull-up and push-down
      maneuvers. Furthermore, a mathematical optimization method is used for
      determining that bounding flight mode which yields the minimum energy expenditure
      per range. Thus, it can be shown to what extent bounding flight is
      aerodynamically superior to continuous flapping flight, yielding a reduction in
      the energy expenditure in the speed range practically above the maximum range
      speed. Moreover, the role of the body lift for the efficiency of bounding flight
      is identified and quantified. Introducing an appropriate non-dimensionalization
      of the relations describing the bird's flight dynamics, results of generally
      valid nature are derived for the addressed items.

PMID- 21875603
TI  - Effects of acute hypercapnia on the amplitude of cerebrovascular pulsation in
      humans registered with a non-invasive method.
AB  - AIM: The aim of the study was to assess non-invasively the effects of acute
      hypercapnia on the amplitude of cerebrovascular pulsation (CVP) in humans.
      METHODS: Experiments were carried out in four male volunteers aged 25, 26, 31 and
      49. Changes in blood flow through the pial arteries were induced using two
      interventions: (A) breathing a gas mixture containing 5% CO(2) for 2 minutes and
      (B) intravenous administration of 1g acetazolamide. The amplitude of CVP and
      width of subarachnoid space (SAS) were measured non-invasively using near
      infrared transillumination/backscattering sounding (NIR-T/BSS), while cerebral
      blood flow was assessed by single photon emission computed tomography (SPECT) and
      mean blood flow velocity in the left anterior cerebral artery by transcranial
      Doppler. RESULTS: Inhalation of a gas mixture containing 5% CO(2) evoked an
      increase in the amplitude of CVP (202.5% +/- SE 10.1), normalized number of
      counts (22.6% +/- SE 3.5%) and mean blood flow velocity in the left cerebral
      anterior artery (37.6%+/- SE 11.7%), while resistive index decreased (-8.7% +/-
      SE 2.3%) and the width of SAS decreased (-8.0 +/- SE 0.45). Acetazolamide also
      produced an increase in the amplitude of CVP (23.7% +/- SE 5.4%), normalized
      number of counts (7.9% +/- SE 1.1%), and mean blood flow velocity in the left
      cerebral anterior artery (62.8% +/- SE 13.7%), while resistive index decreased (
      7.9% +/- SE 1.7%), and the width of SAS decreased (-13.4% +/- SE 3.4%).
      CONCLUSION: Acute hypercapnia causes an increase in the amplitude of CVP
      pulsation in humans. NIR-T/BSS allows for non-invasive bedside monitoring of the
      amplitude of CVP. NIR-T/BSS is consistent with transcranial Doppler and SPECT.

PMID- 21875604
TI  - Obesity is associated with impaired endothelial function in the postprandial
      state.
AB  - Adequate microvascular perfusion is essential for the regulation of tissue
      metabolism. Therefore, defects in microvascular function may play a role in
      obesity-associated insulin resistance. Steady-state hyperinsulinemia during a
      euglycemic hyperinsulinemic clamp stimulates endothelium-dependent vasodilation
      and capillary recruitment, which contribute to increased glucose uptake. These
      phenomena have been shown to be blunted in obesity. If insulin's effects on
      microcirculatory function indeed play a physiological role in regulating insulin
      mediated glucose uptake, such effects should be demonstrable not only during
      steady-state hyperinsulinemia, but also after meal ingestion. We investigated
      whether similar responses occur after ingestion of a glucose load or a mixed
      meal. We examined the effects of a glucose drink, a mixed meal drink, or a
      control drink (water) on skin capillary density (i.e. baseline capillary density,
      hyperemic capillary recruitment, and density during venous congestion, using
      capillaroscopy) and skin endothelium-(in)dependent vasodilation (using laser
      Doppler flowmetry with iontophoresis of acetylcholine and sodium nitroprusside)
      in 20 lean and 19 obese individuals. In lean individuals, neither the glucose nor
      the mixed meal drink induced a significant effect on capillary density or
      endothelium-(in)dependent vasodilation. Possibly this is related to the modest
      plasma insulin levels as compared to the insulin clamp. In obese individuals, the
      mixed meal drink, compared to the control drink, decreased baseline skin
      perfusion (P<0.05) and acetylcholine-mediated vasodilation (P<0.05), while no
      effect of the drinks on capillary density was found. Compared to lean
      individuals, obese individuals had impaired acetylcholine-mediated vasodilation
      after meal ingestion (P=0.02). The latter findings are consistent with impaired
      postprandial microvascular function in obesity.

PMID- 21875605
TI  - Correlation analysis between prefrontal oxygenation oscillations and cerebral
      artery hemodynamics in humans.
AB  - The objective of this study is to assess the correlation between the prefrontal
      cerebral oxygenation oscillations measured by near-infrared spectroscopy (NIR)
      and cerebral artery hemodynamic parameters as measured by transcranial Doppler
      (TCD). A total of thirty subjects were recruited from the university to
      participate in this study. The cerebral oxygenation signal and TCD hemodynamic
      parameters were monitored on separate days. The cerebral oxygenation signal was
      monitored for 10 min from the left prefrontal lobe using NIRS. TCD monitoring was
      performed to measure the hemodynamic parameters including end diastolic, peak
      systolic, and mean cerebral blood flow velocities. Pulsatility index (PI) and
      resistance index (RI) were calculated automatically. With spectral analysis based
      on wavelet transform of NIR signal, five frequency intervals were identified (I,
      0.005-0.02 Hz, II, 0.02-0.06 Hz, III, 0.06-0.15 Hz, IV, 0.15-0.50 Hz and V, 0.50
      2.0 Hz). Significant negative correlation was found between the cerebral [Hb] and
      [HbO(2)] oscillations in frequency intervals from I to V and the PI or RI in left
      external carotid artery (ECA) (p<0.005). Also weak negative correlation was found
      between the cerebral [Hb] and [HbO(2)] oscillations in frequency intervals III,
      IV, V and the mean velocity in left middle cerebral artery (MCA) (p<0.05). The
      results suggested that the cerebral oscillations measured from the frontal lobe
      were closely related to the pulsatility of ECA and reflect partly the vessel
      stiffness of MCA.

PMID- 21875606
TI  - Impaired nucleotide excision repair pathway as a possible factor in pathogenesis
      of head and neck cancer.
AB  - Tobacco smoking is one of the major risk factors in pathogenesis of head and neck
      squamous cell carcinomas (HNSCC). Many of the chemical compounds present in
      tobacco are well-known carcinogens which form adducts with DNA. Cells remove
      these adducts mainly by the nucleotide excision repair pathway (NER). NER also
      eliminates a broad spectrum of pyrimidine dimers (CPD) and photo-products (6-4PP)
      induced by UV-radiation or DNA cross-links after cisplatin anti-cancer treatment.
      In this study DNA damage and repair was examined in peripheral blood lymphocytes
      obtained from 20 HNSCC patients and 20 healthy controls as well as HTB-43 larynx
      and SSC-25 tongue cancer cell lines. DNA repair kinetics in the examined cells
      after cisplatin or UV-radiation treatment were investigated using alkaline comet
      assay during 240min of post-treatment incubation. MTT assay was used to analyse
      cell viability and the Annexin V-FITC kit specific for kinase-3 was employed to
      determine apoptosis after treating the cells with UV-radiation at dose range from
      0.5 to 60J/m(2). NER capability was assessed in vitro with cell extracts by the
      use of a bacterial plasmid irradiated with UV-light as a substrate for the
      repair. The results show that lymphocytes from HNSCC patients and HTB-43 or SSC
      25 cancer cells were more sensitive to genotoxic treatment with UV-radiation and
      displayed impaired DNA repair. Also evidenced was a higher rate of apoptosis
      induction after UV-radiation treatment of lymphocytes from the HNSCC patients and
      the HTB-43 cancer cells than after treatment of those from healthy donors.
      Finally, our results showed that there was a significant decrease in NER capacity
      in HTB-43 or SSC-25 cancer cells as well as in peripheral blood lymphocytes of
      HNSCC patients compared to controls. In conclusion, we suggest that the impaired
      NER pathway might be a critical factor in pathogenesis of head and neck cancer.

PMID- 21875608
TI  - Neuropharmacology special issue on posttraumatic stress disorder (PTSD): current
      state of the art in clinical and preclinical PTSD research.

PMID- 21875610
TI  - Tactile rod bisection in the absence of visuo-spatial processing in children, mid
      age and older adults.
AB  - The effect of age on tactile rod bisection is explored in an attempt to fully
      understand lateralized biases that are not driven by prior experience or visual
      processing. In Experiment 1, a total of 549 healthy participants aged between 3
      and 84 years of age, divided into eight age groups, used touch alone without
      vision to bisect one wooden rod. Participants across all age groups, except those
      approaching or in adolescence, showed pseudoneglect on tactile rod bisection. In
      Experiment 2 a total of 72 healthy participants aged between 6 and 96 years old,
      divided into three age groups, used touch alone without vision to bisect three
      wooden rods of different length. Experiment 2 showed pseudoneglect across the
      full adult life span and most notably in the oldest participants. For the
      youngest participants there was not a significant pseudoneglect bias but there
      was a significant effect of gender with females showing greater leftward bias
      than males. When participants scanned and bisected the rods starting from the
      right-hand side, pseudoneglect was significantly enhanced; again this bias
      interacted with age. The results suggest that the right hemisphere exerts an
      early capacity to orient attention contralaterally and that this capacity
      continues in middle and older adulthood which is inconsistent with current models
      of cognitive ageing. The findings are discussed in terms of how the right
      hemisphere preferentially orients attention leftward in the absence of direct
      visuo-spatial processing across lifespan and how this may be modulated by
      variables like gender and starting position.

PMID- 21875609
TI  - Predictability affects early perceptual processing of word onsets in continuous
      speech.
AB  - Event-related potential (ERP) evidence indicates that listeners selectively
      attend to word onsets in continuous speech, but the reason for this preferential
      processing is unknown. The current study measured ERPs elicited by syllable
      onsets in an artificial language to test the hypothesis that listeners direct
      attention to word onsets because their identity is unpredictable. Both before and
      after recognition training, participants listened to a continuous stream of six
      nonsense words arranged in pairs, such that the second word in each pair was
      completely predictable. After training, first words in pairs elicited a larger
      negativity beginning around 100 ms after onset. This effect was not evident for
      the completely predictable second words in pairs. These results suggest that
      listeners are most likely to attend to the segments in speech that they are least
      able to predict.

PMID- 21875611
TI  - Domoic acid induced status epilepticus promotes aggressive behavior in rats.
AB  - Domoic acid (DA), a naturally occurring environmental toxin, has been observed to
      induce status epilepticus in humans, sea lions and pelicans. In a recent Sprague
      Dawley rat model, domoic acid dosing induced a state of status epilepticus which,
      after a symptom-free latent period without further dosing, progressed to
      recurrent spontaneous seizures, a hallmark of epilepsy. Certain individuals in
      this study also developed unusual behavioral changes, in particular an atypical
      aggression towards conspecifics. In this report we characterized the progression
      of aggressive behaviors after DA-induced status epilepticus and explored the
      relationship between aggressive behavior and recurrent spontaneous seizures.
      Experimental studies in this laboratory rat model are particularly relevant to
      California sea lions (Zapholus californianus), which show a spectrum of both
      epileptic and unusual behaviors, including aggression towards conspecifics in
      rehabilitation facilities, weeks to months after suspected exposure to domoic
      acid in the wild.

PMID- 21875607
TI  - Asenapine effects on cognitive and monoamine dysfunction elicited by subchronic
      phencyclidine administration.
AB  - PURPOSE: Repeated, intermittent administration of the psychotropic NMDA
      antagonist phencyclidine (PCP) to laboratory animals causes impairment in
      cognitive and executive functions, modeling important sequelae of schizophrenia;
      these effects are thought to be due to a dysregulation of neurotransmission
      within the prefrontal cortex. Atypical antipsychotic drugs have been reported to
      have measurable, if incomplete, effects on cognitive dysfunction in this model,
      and these effects may be due to their ability to normalize a subset of the
      physiological deficits occurring within the prefrontal cortex. Asenapine is an
      atypical antipsychotic approved in the US for the treatment of schizophrenia and
      for the treatment, as monotherapy or adjunctive therapy to lithium or valproate,
      of acute manic or mixed episodes associated bipolar I disorder. To understand its
      cognitive and neurochemical actions more fully, we explored the effects of short-
      and long-term dosing with asenapine on measures of cognitive and motor function
      in normal monkeys and in those previously exposed for 2 weeks to PCP; we further
      studied the impact of treatment with asenapine on dopamine and serotonin turnover
      in discrete brain regions from the same cohort. METHODS: Monkeys were trained to
      perform reversal learning and object retrieval procedures before twice daily
      administration of PCP (0.3 mg/kg intra-muscular) or saline for 14 days. Tests
      confirmed cognitive deficits in PCP-exposed animals before beginning twice daily
      administration of saline (control) or asenapine (50, 100, or 150 MUg/kg, intra
      muscular). Dopamine and serotonin turnover were assessed in 15 specific brain
      regions by high-pressure liquid chromatography measures of the ratio of parent
      amine to its major metabolite. RESULTS: On average, PCP-treated monkeys made
      twice as many errors in the reversal task as did control monkeys. Asenapine
      facilitated reversal learning performance in PCP-exposed monkeys, with
      improvements at trend level after 1 week of administration and reaching
      significance after 2-4 weeks of dosing. In week 4, the improvement with asenapine
      150 MUg/kg (p = 0.01) rendered the performance of PCP-exposed monkeys
      indistinguishable from that of normal monkeys without compromising fine motor
      function. Asenapine administration (150 MUg/kg twice daily) produced an increase
      in dopamine and serotonin turnover in most brain regions of control monkeys and
      asenapine (50-150 MUg/kg) increased dopamine and serotonin turnover in several
      brain regions of subchronic PCP-treated monkeys. No significant changes in the
      steady-state levels of dopamine or serotonin were observed in any brain region
      except for the central amygdala, in which a significant depletion of dopamine was
      observed in PCP-treated control monkeys; asenapine treatment reversed this
      dopamine depletion. A significant decrease in serotonin utilization was observed
      in the orbitofrontal cortex and nucleus accumbens in PCP monkeys, which may
      underlie poor reversal learning. In the same brain regions, dopamine utilization
      was not affected. Asenapine ameliorated this serotonin deficit in a dose-related
      manner that matched its efficacy for reversing the cognitive deficit.
      CONCLUSIONS: In this model of cognitive dysfunction, asenapine produced
      substantial gains in executive functions that were maintained with long-term
      administration. The cognition-enhancing effects of asenapine and the
      neurochemical changes in serotonin and dopamine turnover seen in this study are
      hypothesized to be primarily related to its potent serotonergic and noradrenergic
      receptor binding properties, and support the potential for asenapine to reduce
      cognitive dysfunction in patients with schizophrenia and bipolar disorder.

PMID- 21875612
TI  - No control in orientation search: the effects of instruction on oculomotor
      selection in visual search.
AB  - The present study aimed to investigate whether people can selectively use
      salience information in search for a target. Observers were presented with a
      display consisting of multiple homogeneously oriented background lines and two
      orientation singletons. The orientation singletons differed in salience, where
      salience was defined by their orientation contrast relative to the background
      lines. Observers had the task to make a speeded eye movement towards a target,
      which was either the most or the least salient element of the two orientation
      singletons. The specific orientation of the target was either constant or
      variable over a block of trials such that observers had varying knowledge
      concerning the target identity. The results demonstrated that instruction -
      whether people were instructed to move to the most or the least salient item -
      only minimally affected the results. Short-latency eye movements were completely
      salience driven; here it did not matter whether people were searching for the
      most or least salient element. Long-latency eye movements were marginally
      affected by instruction, in particular when observers knew the target identity.
      These results suggest that even though people use salience information in
      oculomotor selection, they cannot use this information in a goal-driven manner.
      The results are discussed in terms of current models on visual selection.

PMID- 21875613
TI  - The challenges of UV-induced immunomodulation for children's health.
AB  - Exposure to solar ultraviolet radiation (UVR) is recognised to have both
      beneficial and harmful effects on human health. With regard to immune responses,
      it can lead to suppression of immunity and to the synthesis of vitamin D, a
      hormone that can alter both innate and adaptive immunity. The consequences in
      children of such UV-induced changes are considerable: first there are positive
      outcomes including protection against some photoallergic (for example polymorphic
      light eruption) and T cell-mediated autoimmune diseases (for example multiple
      sclerosis) and asthma, and secondly there are negative outcomes including an
      increased risk of skin cancer (squamous cell carcinoma, basal cell carcinoma and
      cutaneous malignant melanoma) and less effective control of several infectious
      diseases. Many uncertainties remain regarding the amount of sun exposure that
      would provide children with the most effective responses against the variety of
      immunological challenges that they are likely to experience.

PMID- 21875614
TI  - Withdrawal from repeated treatment with amphetamine reduces novelty-seeking
      behavior and enhances environmental habituation in mice.
AB  - Anhedonia associated with a dysphoric state is an important feature of
      amphetamine withdrawal in humans. We aimed to investigate the effects of
      amphetamine withdrawal on two motivation-related behaviors in mice: novelty
      seeking and environmental habituation. Because anxiety can interfere with the
      behavioral outcome of other tasks, amphetamine-withdrawn mice were also evaluated
      in the elevated plus maze. Swiss male mice (three months old) were treated with
      2.0mg/kg amphetamine for 13 days, every other day, in their home cages (a total
      of seven injections). Twenty-four hours after withdrawal from drug treatment,
      mice were tested in a free-choice novelty apparatus containing one familiar and
      one novel compartment or in the elevated plus maze. Novelty-seeking behavior was
      assessed by comparing the time spent in the novel compartment vs. the familiar
      compartment, whereas environmental habituation was concomitantly evaluated by the
      time-response curve of total locomotion (novel+familiar). Novelty seeking was
      decreased during amphetamine withdrawal, and this result was not associated with
      changes in the anxiety-like behavior of mice. Additionally, amphetamine
      withdrawal enhanced environmental habituation. The concomitant decrease in
      novelty seeking and the increase in environmental habituation seem to be related
      to amphetamine withdrawal-induced anhedonia. Thus, the model proposed here could
      be used as a tool for the study of mechanisms and potential treatment of the
      anhedonic behavioral consequences of psychostimulant withdrawal.

PMID- 21875615
TI  - Preserved learning and memory following 5-fluorouracil and cyclophosphamide
      treatment in rats.
AB  - Some patients experience enduring cognitive impairment after cancer treatment, a
      condition termed "chemofog". Animal models allow assessment of chemotherapy
      effects on learning and memory per se, independent of changes due to cancer
      itself or associated health consequences such as depression. The present study
      examined the long-term learning and memory effects of a chemotherapy cocktail
      used widely in the treatment of breast cancer, consisting of 5-fluorouracil (5FU)
      and cyclophosphamide (CYP). Eighty 5-month old male F344 rats received contextual
      and cued fear conditioning before treatment with saline, or a low or high dose
      drug cocktail (50mg/kg CYP and 75 mg/kg 5FU, or 75 mg/kg CYP and 120 mg/kg 5FU,
      i.p., respectively) every 30 days for 2 months. After a 2-month, no-drug
      recovery, both long-term retention and new task acquisition in the water maze and
      14-unit T-maze were assessed. Neither dose of the CYP/5FU cocktail impaired
      retrograde fear memory despite marked toxicity documented by enduring weight loss
      and 50% mortality at the higher dose. Acquisition in the water maze and Stone
      maze was also normal relative to controls in rats treated with CYP/5FU. The
      results contribute to a growing literature suggesting that learning and memory
      mediated by the hippocampus can be relatively resistant to chemotherapy. Future
      investigation may need to focus on assessments of processing speed, executive
      function and attention, and the possible interactive contribution of cancer
      itself and aging to the post-treatment development of cognitive impairment.

PMID- 21875616
TI  - Incidence of invasive pneumococcal disease among elderly people in Southern
      Catalonia, Spain, 2002-2009: an increase in serotypes not contained in the
      heptavalent conjugate vaccine.
AB  - Population-based surveillance study conducted among persons >= 65 years old in
      Southern Catalonia, Spain during 2002-2009. All cases with isolation of
      pneumococcus from normally sterile bodily fluids were included. Incidence rates
      of invasive pneumococcal disease (IPD) as well as rates of infections caused by
      serotypes included in the heptavalent pneumococcal conjugate vaccine (PCV7) and
      the 23-valent polysaccharide pneumococcal vaccine (PPV23) were compared for early
      (2002-2005) and contemporary (2006-2009) periods. Mean incidence rate (per
      100,000 population-year) of IPD across study period was 48.0 [95% CI (confidence
      interval): 30.1-72.5]. Incidence rates for PCV7 serotypes slightly decreased by
      21% between 2002-2005 and 2006-2009 (from 9.2 to 7.3; p = 0.511) whereas rates of
      IPD due to nonPCV7 serotypes largely increased by 172% (from 15.6 to 42.4; p <
      0.001) during the same period. For PPV23 but nonPCV7 types, incidence rates
      increased by 146% (from 10.9 to 26.9; p < 0.001) whereas rates for nonPPV23
      serotypes increased by 237% (from 4.6 to 15.5; p = 0.001). As an overall effect
      of these changes, the incidence of all IPD increased by a significant 69% (95%
      CI: 29%-110%). Specific incidence rates of serotypes 6A (from 1.7 to 4.1; p =
      0.182), 7F (from 1.7 to 5.7; p = 0.052) and 19A (from 0.6 to 6.2; p = 0.004)
      substantially increased between both periods. According to these findings,
      Southern Catalonia region can be classified as a mesoendemic area of pneumococcal
      infections among elderly people, with a recent increase incidence of some nonPCV7
      serotypes (especially 19A).

PMID- 21875617
TI  - Method of euthanasia affects amygdala plasticity in horizontal brain slices from
      mice.
AB  - An important consideration in any terminal experiment is the method used for
      euthanizing animals. Although the prime consideration is that the method is
      humane, some methods can have a dramatic impact on experimental outcomes. The
      standard inhalant anesthetic for experiments in brain slices is isoflurane, which
      replaced the flammable ethers used in the pioneer days of surgery. To our
      knowledge, there are no data available evaluating the effects of the method of
      euthanasia on plasticity changes in brain slices. Here, we compare the magnitude
      of long-term potentiation (LTP) and long-term depression (LTD) in the lateral
      nucleus of the amygdala (LA) after euthanasia following either ether or
      isoflurane anesthesia, as well as in mice decapitated without anesthesia. We
      found no differences in input-output curves using different methods of
      euthanasia. The LTP magnitude did not differ between ether and normal isoflurane
      anesthesia. After deep isoflurane anesthesia LTP induced by high frequency
      stimulation of cortical or intranuclear afferents was significantly reduced
      compared to ether anesthesia. In contrast to ether anesthesia and decapitation
      without anesthesia, the low frequency stimulation of cortical afferents induced a
      reliable LA-LTD after deep isoflurane anesthesia. Low frequency stimulation of
      intranuclear afferents only caused LTD after pretreatment with ether anesthesia.
      The results demonstrate that the method of euthanasia can influence brain
      plasticity for hours at least in the interface chamber. Therefore, the method of
      euthanasia is an important consideration when brain plasticity will be evaluated.

PMID- 21875618
TI  - Development of an indirect immunofluorescence assay for diagnosis of bovine viral
      diarrhoea virus on ear notch tissue samples in cattle infected persistently.
AB  - Bovine viral diarrhoea virus (BVDV) causes a disease that has a wide range of
      clinical symptoms in domestic and wild ruminants. It is a major problem in cattle
      and causes significant economic losses in the cattle industry. The virus infects
      bovines of all ages and causes both immunosuppression and reproductive,
      respiratory and digestive disorders. Cattle infected persistently, as a
      continuing source of the virus and the main factor in transmission of the disease
      between and among herds, are the main source of BVDV and a primary factor in the
      epidemiology of the disease. To determine whether a BVDV infection is persistent,
      two samples should be taken at 3-4 week intervals and tested for the virus
      antigen. Animal sera, whole blood, organ and ear notch tissue samples can be used
      for BVDV diagnosis. In ear notch tissue, viral antigen can be detected by an
      antigen enzyme-linked immunosorbent assay (antigen ELISA), immunohistochemistry
      (IHC) and reverse-transcription polymerase chain reaction (RT-PCR). This paper
      describes the development and implementation of an indirect immunofluorescence
      (IF) method using ear notch tissue samples for diagnosis of cattle infected
      persistently. Results obtained by this method show that IF is a good alternative
      to RT-PCR and antigen ELISA and can be a quick and accurate method in diagnosis
      of BVDV in cattle infected persistently with this virus.

PMID- 21875619
TI  - Prediction of drug-resistance in HIV-1 subtype C based on protease sequences from
      ART naive and first-line treatment failures in North India using genotypic and
      docking analysis.
AB  - Genotyping reveal emergence of drug resistance (DR)-related mutations in HIV-1
      protease (PR) gene in the first-line treatment failure patients as per Stanford
      DR database. In order to have a subtype C specific prediction model, a three
      dimensional structure of local wild type C variant is created and the identified
      mutations were introduced to assess the mutational effects on protease inhibitors
      (PI) in a homology model. We estimated viral load, CD4 count and conducted DR
      genotyping in HIV isolates from 129 therapy naive and 20 first-line treatment
      failure individuals. Several genotypic variations, as compared to subtype B
      sequence in the Stanford gene database were detected in HIV-1 subtype C isolates
      from treatment naive individuals. Among these, nine mutations (12S, 15V, 19I,
      36I, 41K, 63P, 69K, 89M, 93L) occurred in more than 60% of the isolates and were
      considered as local wild type for molecular modelling studies. No major mutations
      were seen in the PR sequences in isolates from treatment-naive individuals,
      although isolates from two patients had T74S mutation, known to be associated
      with reduced susceptibility to nelfinavir (NFV) and a combination of M36I, H69K
      and L89M mutations found in isolates from 77 patients (59.7%), considered to be
      conferring resistance to tipranavir (TPV) according to ANRS algorithm. Among the
      first-line treatment failures, an isolate from one patient showed L33F, I47T,
      M46G, and G48E mutations conferring intermediate resistance to saquinavir (SQV)
      and lopinavir (LPV). Though the docking energy scores are in agreement with this
      interpretation for SQV, it, however, indicated these mutations to be causing
      intermediate to high level resistance to atazanavir (ATV) and tipranavir (TPV)
      but making it susceptible to LPV. The patient finally responded to a second-line
      regimen containing 3TC, AZT and LPV with significant viral suppression. All the
      DR genotyping studies analyse the results using available databases which are all
      based on subtype B specific sequences. The proposed homology model in this study
      is unique, as it may predict subtype C specific susceptibility criteria for the
      available PIs.

PMID- 21875620
TI  - In silico study supports the efficacy of a reduced dose regimen for stavudine.
AB  - Stavudine (d4T) is used extensively as part of HAART in resource poor settings,
      despite its toxicities. The revised WHO guidelines specify replacement of d4T
      with less toxic but more expensive drugs when feasible, and that d4T doses be
      standardized to 30 mg twice daily (bid) (irrespective of body-weight), from the
      approved 40 mg bid in adults (body-weight >=60 kg). Therefore, an in silico
      population pharmacokinetic and biochemical model was utilized to compare relative
      efficacies of the two doses in humans. Assessment of predicted quartile ranges of
      simulated concentrations of the triphosphate of d4T suggested sufficient trough
      concentrations to inhibit wild type HIV-1 reverse transcriptase at the reduced
      dose, lending support to the revised WHO recommendations.

PMID- 21875621
TI  - The sensitivity of two-dimensional hindlimb joint kinematics analysis in
      assessing functional recovery in rats after sciatic nerve crush.
AB  - Walking analysis in the rat is increasingly used to assess functional recovery
      after peripheral nerve injury. Here we assess the sensitivity and specificity of
      hindlimb joint kinematics measures during the rat gait early after sciatic nerve
      crush injury (DEN), after twelve weeks of recovery (REINN) and in sham-operated
      controls (Sham) using discriminant analysis. The analysis addressed gait
      spatiotemporal variables and hip, knee and ankle angle and angular velocity
      measures during the entire walking cycle. In DEN animals, changes affected all
      studied joints plus spatiotemporal parameters of gait. Both the spatiotemporal
      and ankle kinematics parameters recovered to normality within twelve weeks. At
      this time point, some hip and knee kinematics values were still abnormal when
      compared to sham controls. Discriminant models based on hip, knee and ankle
      kinematics displayed maximal sensitivity to identify DEN animals. However, the
      discriminant models based on spatiotemporal and ankle kinematics data showed a
      poor performance when assigning animals to the REINN and Sham groups. Models
      using hip and knee kinematics during walking showed the best sensitivity to
      recognize the reinnervated animals. The model construed on the basis of hip joint
      kinematics was the one combining highest sensitivity with robustness and high
      specificity. It is concluded that ankle joint kinematics fails in detecting minor
      functional deficits after long term recovery from sciatic nerve crush and
      extending the kinematic analysis during walking to the hip and knee joints
      improves the sensitivity of this functional test.

PMID- 21875622
TI  - Stereotactic functional mapping of the cat motor cortex.
AB  - Epidural motor cortex stimulation is an increasingly used method to control
      refractory neuropathic pain although its mechanisms of action remain poorly
      understood. Animal models are currently developed that allow reproducing the
      conditions of this neurosurgical approach and clarifying its mechanisms. In this
      study we validate a new stereotactic functional map of the cat motor cortex
      carried out in epidural conditions, thus allowing future experimentations that
      closely mimic the technique used in humans.

PMID- 21875623
TI  - Adaptive changes in zebrafish brain in dominant-subordinate behavioral context.
AB  - Male zebrafish were held in dyadic social stress situation for a period of 5
      days, to characterize stress coping styles and to investigate the role of the
      underlying neuroendocrine mechanisms in establishing dominant-subordinate
      relationships. A strong consistent dominant-subordinate relationship was formed
      in ten out of the sixteen pairs of fish (62.5%). Both dominant (DOM) and
      subordinate (SUB) individuals showed statistically significant higher trunk
      cortisol concentration than controls. Expression of genes encoding proteins
      involved in the functioning of the hypothalamus-hypophysis-interrenal axis
      (corticotropin releasing factor, CRF; glucocorticoid receptor, GR;
      mineralocorticoid receptor, MR); arginine vasotocin, AVT), in the biosynthesis
      and catabolism of catecholamines (tyrosine hydroxylase, TH1 and TH2; DOPA
      decarboxylase, DDC), dopamine beta-hydroxylase, DBH; catechol-O-methyl
      transferase, COMT), in the biosynthesis of histamine (histidine decarboxylase,
      HDC) and in the general stress response (galanin, GAL; hypocretin/orexin, Hcrt)
      was examined. The MR/GR ratio was higher in dominant and subordinate fish than in
      controls (P=0.016). The mRNA levels of TH2 and HDC were up-regulated in DOM, of
      AVT in SUB, while COMT mRNA levels were down-regulated in both DOM and SUB
      compared to control fish. In addition, mRNA levels of hypocretin/orexin (Hcrt)
      were up-regulated in dominant compared to subordinate and control males. There
      was a statistically significant correlation between mRNA expression levels of
      TH2, HDC, Hcrt, GR, MR and CRF genes. The obtained results provide new evidences
      for the use of zebrafish as an animal model to study social stress and allostasis
      in vertebrates.

PMID- 21875624
TI  - Activation of ER stress and apoptosis by hydrogen peroxide in HeLa cells:
      protective role of mild heat preconditioning at 40 degrees C.
AB  - The accumulation of misfolded proteins in the endoplasmic reticulum (ER) during
      stress conditions causes activation of the unfolded protein response (UPR). If
      this adaptive response cannot restore ER homeostasis, cells undergo ER-mediated
      apoptosis. This study determines whether thermotolerance developed at a mild
      temperature (40 degrees C) can alter induction of ER-mediated stress and
      apoptosis by H(2)O(2) in HeLa cells. Protein expression of PERK, p-PERK,
      eIF2alpha and p-eIF2alpha was increased in thermotolerant compared to non
      thermotolerant cells. Thus, mild thermotolerance enhanced pro-survival effects of
      the PERK/eIF2alpha branch of the UPR. A short exposure (15 min) of cells to
      H(2)O(2) (15-50 MUM) activated the UPR: expression of p-PERK, p-eIF2alpha and p
      IRE1alpha increased, and ATF6 cleavage occurred. Longer exposure (1-3h) to
      H(2)O(2) induced ER-mediated apoptosis, whereby CHOP expression increased, and
      enzymatic activity of calpain, caspase-7, -4, -12 and -9 also increased. These
      pro-apoptotic events and clonogenic cell killing were all diminished in
      thermotolerant cells. Activation of caspases-4/-12 was decreased by the calcium
      chelator BAPTA-AM, and by inhibitors of calpain and caspase-7, confirming the
      roles of calcium, calpain and caspase-7 in activation of ER-mediated apoptosis by
      H(2)O(2). In thermotolerant cells with decreased levels of PERK by siRNA, there
      was partial reversal of resistance to H(2)O(2)-induced apoptosis. Hence, a causal
      connection exists between the ER stress response and resistance to H(2)O(2)
      induced apoptosis. Mild thermotolerance plays a protective, anti-apoptotic role
      by increasing the threshold for induction of ER-mediated apoptosis by H(2)O(2).
      Moreover, the adaptive response (UPR) dominates during milder H(2)O(2) stress,
      whereas ER-mediated apoptosis occurs during more severe stress.

PMID- 21875625
TI  - Bcl-x(L) overexpression delays the onset of autophagy and apoptosis in
      hyperosmotic recombinant Chinese hamster ovary cell cultures.
AB  - Hyperosmolality in recombinant Chinese hamster ovary (rCHO) cell cultures induces
      autophagy and apoptosis. To investigate the effect of Bcl-x(L) overexpression on
      autophagy and apoptosis in hyperosmotic rCHO cell cultures, an erythropoietin
      (EPO)-producing rCHO cell line with regulated Bcl-x(L) overexpression was
      subjected to hyperosmolality resulting from NaCl addition in a batch culture and
      nutrient supplementation in a fed-batch culture. In the batch culture, Bcl-x(L)
      overexpression suppressed apoptosis, as evidenced by a decreased amount of
      cleaved caspase-7 and PARP. Concurrently, Bcl-x(L) overexpression also delayed
      autophagy, as indicated by reduced LC3 conversion, from LC3-I to LC3-II. As a
      result, the cell viability and EPO production were improved by Bcl-x(L)
      overexpression. In the fed-batch culture, the simultaneous application of Bcl
      x(L) overexpression and nutrient feeding increased the culture longevity and
      maximum EPO concentration. Taken together, Bcl-x(L) overexpression delayed
      autophagy and apoptosis in hyperosmotic rCHO cell cultures, resulting in
      increased EPO production.

PMID- 21875626
TI  - A point mutation in the Medicago sativa GSA gene provides a novel, efficient,
      selectable marker for plant genetic engineering.
AB  - Bacterial selectable marker genes (SMG) conferring antibiotic resistance are
      valuable tools in plant genetic engineering, but public concern and regulatory
      requirements have stimulated the development of alternative selection systems. We
      have previously demonstrated that a mutated Synechococcus elongatus HemL gene
      encoding glutamate 1-semialdehyde aminotransferase (GSA) is an efficient SMG in
      alfalfa. In fact, GSA is irreversibly inhibited by gabaculine (3-amino-2,3
      dihydrobenzoic acid), but the mutated enzyme is gabaculine insensitive. With the
      aim to develop a plant derived SMG, we cloned and sequenced the Medicago sativa
      GSA cDNA and reproduced one of the two mutations associated with gabaculine
      resistance in Synechococcus, a transversion resulting in a methionine to
      isoleucine (M->I) substitution. This mutated gene was assessed as a SMG in
      tobacco and alfalfa Agrobacterium transformation, in comparison with the wild
      type gene. In tobacco, about 43% of the leaf explants produced green shoots,
      whereas in alfalfa 47% of the explants produced green embryos in the presence of
      30 MUM gabaculine when the M->I GSA was introduced. Escapes were absent in
      tobacco and only 6% in alfalfa. No effect on the plant phenotype was noticed. We
      propose this new SMG as a widely acceptable alternative to those currently used.

PMID- 21875627
TI  - Metabolic engineering of Pseudomonas fluorescens for the production of vanillin
      from ferulic acid.
AB  - Vanillin is one of the most important flavors in the food industry and there is
      great interest in its production through biotechnological processes starting from
      natural substrates such as ferulic acid. Among bacteria, recombinant Escherichia
      coli strains are the most efficient vanillin producers, whereas Pseudomonas spp.
      strains, although possessing a broader metabolic versatility, rapidly metabolize
      various phenolic compounds including vanillin. In order to develop a robust
      Pseudomonas strain that can produce vanillin in high yields and at high
      productivity, the vanillin dehydrogenase (vdh)-encoding gene of Pseudomonas
      fluorescens BF13 strain was inactivated via targeted mutagenesis. The results
      demonstrated that engineered derivatives of strain BF13 accumulate vanillin if
      inactivation of vdh is associated with concurrent expression of structural genes
      for feruloyl-CoA synthetase (fcs) and hydratase/aldolase (ech) from a low-copy
      plasmid. The conversion of ferulic acid to vanillin was enhanced by optimization
      of growth conditions, growth phase and parameters of the bioconversion process.
      The developed strain produced up to 8.41 mM vanillin, which is the highest final
      titer of vanillin produced by a Pseudomonas strain to date and opens new
      perspectives in the use of bacterial biocatalysts for biotechnological production
      of vanillin from agro-industrial wastes which contain ferulic acid.

PMID- 21875628
TI  - Use of GFP fusions for the isolation of Escherichia coli strains for improved
      production of different target recombinant proteins.
AB  - High level expression of a recombinant gene results in growth arrest, followed by
      overgrowth by non-productive derivatives. Two methods are described for the
      isolation of E. coli BL21* strains that are improved hosts for recombinant
      protein production. Both are based upon the observations (i) that fluorescence of
      a C-terminal GFP tag is a reliable reporter of the production and correct folding
      of the N-terminal target domain; and (ii) rare mutants arise spontaneously that
      remain productive during long periods of high level recombinant protein
      production. The first method relies upon identifying these mutants amongst
      colonies on agar plates; the other exploits fluorescence activated cell sorting.
      Although identical mutations in the regulatory region of the T7 polymerase gene
      were found in all of the improved host strains isolated, they differed in their
      ability to accumulate the outer membrane protein, Ccp, or a cytoplasmic protein,
      CheY-GFP. Cytochrome c peroxidase activity of recombinant Ccp from one of these
      strains was demonstrated. Changes in levels of T7 polymerase expression are
      therefore insufficient to ensure increased accumulation of all recombinant
      proteins. We demonstrate that the methods described allow strains to be isolated
      that carry other, currently uncharacterised mutations that are required depending
      on the target protein.

PMID- 21875630
TI  - Stages of change for fruit and vegetable intake among patients with
      atherosclerotic disease.
AB  - This paper describes the stages of change in fruit and vegetable intake among
      patients with atherosclerotic disease, identifying demographic, socioeconomic,
      and health predictive factors for each stage of change. It is a cross-sectional
      study of 290 consecutive patients with atherosclerotic disease submitted to
      endovascular procedures in two referral hospitals. The staging algorithm included
      intentional and behavioral criteria, and patients were categorized into "pre
      action" (pre-contemplation, contemplation, and preparation), or "action" (action,
      non-reflective action, and maintenance). Most of the patients were in action for
      the fruits intake (67.9%) and pre-action for the vegetables intake (69.1%). The
      logistic regression analysis for the stages of action change for fruits intake
      has identified as predictive factors, the higher level of education and
      consultation with a cardiologist. For the stages of action change for vegetable
      intake, absence of abdominal obesity, previous cardiac surgery, and consultation
      with dietitian have shown significant association. This study has shown
      differences in the distribution of stages of change for the fruits and vegetable
      intake among the patients with atherosclerotic disease. The different predictive
      factors for the stage of changes for fruits and vegetables suggest that
      approaches of nutritional orientation of the individuals must be distinct for
      each eating behavior.

PMID- 21875629
TI  - Biological and molecular characterization of Soybean yellow common mosaic virus,
      a new species in the genus Sobemovirus.
AB  - A novel soybean-infecting sobemovirus termed Soybean yellow common mosaic virus
      (SYCMV) was characterized. The virus has a single, positive-strand RNA genome of
      4152 nucleotides. The virus contains four putative open reading frames encoding
      P1 (78-566 nt), polyprotein ORF2a (524-2248 nt), polymerase domain ORF2b (1852
      3417 nt), and CP (3227-4030 nt). The entire nucleotide sequence of SYCMV showed
      31.2-71.3% nucleotide identity with the previously known eleven species of
      sobemovirus. In host range analysis of SYCMV, in which twenty one species and
      three different Nicotiana tabacum cultivars belonging to seven families were
      inoculated with the virus, SYCMV had a narrow host range, infecting only Glycine
      max and G. soja. Based on the obtained sequence, full-length clones of SYCMV were
      constructed. Symptoms produced by inoculation with clones were indistinguishable
      from those produced by inoculation with sap from symptomatic plants. Viral RNA
      accumulation of SYCMV was detected in the upper leaves by Northern blotting. This
      indicated that full-length clones of SYCMV were sufficient to produce disease
      symptoms. Genomic organization, the predicted amino acid sequence, and
      phylogenetic analyses with known sobemoviruses confirmed the assignment of SYCMV
      as a new member of the genus Sobemovirus.

PMID- 21875631
TI  - Guillain-Barre syndrome and H1N1 (2009) pandemic influenza vaccination using an
      AS03 adjuvanted vaccine in the United Kingdom: self-controlled case series.
AB  - In 1976 a swine influenza vaccine was associated with an increased risk of
      Guillain-Barre syndrome (GBS). Although subsequent studies did not find an
      increased risk of GBS following seasonal influenza vaccine, there was concern
      that the monovalent H1N1 vaccines developed against the swine influenza pandemic
      of 2009 might increase the risk of GBS. In the UK a split-virion AS03 oil-in
      water adjuvanted vaccine (PandemrixTM) was predominantly used. To determine
      whether the risk of GBS increased after Pandemrix administration, we sought GBS
      cases during the period of vaccine use from neurologists and a patient support
      group, and following the vaccination period from hospital episode statistics
      (HES) in England. We obtained cases' vaccination histories and illness onset
      dates from general practitioners. We determined the relative incidence of GBS in
      the 6 weeks after vaccination using the self-controlled case series method on the
      cases identified in HES. We included 327 GBS cases, of whom 37 received pandemic
      vaccine in the study period, nine of whom developed GBS within 6 weeks of
      vaccination (relative incidence 1.05 [95% confidence interval (CI) 0.37 to
      2.24]). We found no evidence of an increased risk of GBS in the 6 weeks following
      pandemic influenza vaccination.

PMID- 21875632
TI  - Universal peptide vaccines - optimal peptide vaccine design based on viral
      sequence conservation.
AB  - Rapidly mutating viruses such as the hepatitis C virus (HCV), the human
      immunodeficiency virus (HIV), or influenza viruses (Flu) call for highly
      effective universal peptide vaccines, i.e. vaccines that do not only yield broad
      population coverage but also broad coverage of various viral strains. The
      efficacy of such vaccines is determined by multiple properties of the epitopes
      they comprise. Beyond the specific properties of each epitope, properties of the
      corresponding source antigens are of great importance. If a response is mounted
      against viral proteins with a low copy number within the cell or against proteins
      expressed very late, this response may fail to induce lysis of the infected cells
      before budding can take place. We here propose a novel methodology to optimize
      the epitope composition and assembly in order to induce maximum protection. In
      order for a peptide vaccine to yield the best possible universal protection,
      several conditions should be met: (a) an optimal choice of target antigens, (b)
      an optimal choice of highly conserved epitopes, (c) maximum coverage of the
      target population, and (d) the proper ordering of the epitopes in the final
      vaccine to ensure favorable cleavage. We propose a mathematical formalism for
      epitope selection and ordering that balances the constraints imposed by these
      different conditions. Focusing on HCV, HIV, and Flu, we show that not all of the
      conditions can be satisfied for all viruses. Depending on the virus, different
      constraints are harder to fulfill: for Flu, the conservation constraint is
      violated first, while for HIV, it is difficult to focus the response at the
      optimal target antigens. The proposed methodology can be applied to any virus to
      assess the feasibility of optimally combining the above-mentioned constraints.

PMID- 21875634
TI  - Wheezing lower respiratory disease and vaccination of premature infants.
AB  - PURPOSE: Premature infants are at increased risk of wheezing in association with
      respiratory syncytial virus (RSV) and rhinovirus infections. We assess possible
      associations between wheezing and routine vaccinations of premature infants.
      METHODS: We conducted a self-controlled case series (SCCS) study of premature
      infants born at five health maintenance organizations (HMO's) from 1997 to 2002
      (N=18,628). Episodes of medically attended wheezing lower respiratory diseases
      (WLRD) were ascertained from ICD-9 coded database records. Relative risks of WLRD
      during post-vaccination exposure windows were estimated by Cox proportional
      hazard regression with time-dependent vaccine exposure variables, adjusted for
      age, season, and frequency of well-baby visits. RESULTS: WLRD hazard ratios (HR)
      were not significantly elevated for any vaccine type among non-fragile or fragile
      premature infants. Among non-fragile infants the 8-14 days HR was significantly
      reduced for live attenuated MMR (0.68, 0.52-0.88) and Varicella (0.71, 0.53-0.94)
      vaccines, and similarly but insignificantly reduced for infrequently used live
      attenuated OPV vaccine (0.70, 0.46-1.06). There was a smaller significant
      reduction (0.83, 0.69-0.998) in the 15-30 days HR for MMR and a similar but not
      significant reduction (0.86, 0.71-1.05) in the 31-44 days HR for MMR. Hepatitis B
      vaccine (HBV), which is not a live vaccine, had significantly reduced 8-14 days
      (0.84, 0.72-0.98) and 31-44 days (0.88, 0.78-0.98) HRs among non-fragile infants.
      The apparent protective effect of HBV may be confounded by live vaccines
      administered simultaneously with the third dose of HBV. Among fragile infants
      there was a large significant reduction in the 8-14 days HR for live attenuated
      OPV vaccine (0.40, 0.23-0.70) and smaller significant reductions in the 8-14 days
      HR for inactivated DTaP (0.82, 0.71-0.95), Hib (0.83, 0.73-0.96), and PCV7 (0.84,
      0.70-0.997) vaccines. Delays in vaccinating fragile infants may have made
      simultaneous administration of live vaccines and third doses of these inactivated
      vaccines more likely. CONCLUSIONS: We found no evidence of increased WLRD risk
      following routine vaccinations of premature infants. WLRD risk among non-fragile
      premature infants appears to be reduced for a few weeks after live attenuated
      vaccinations.

PMID- 21875633
TI  - Immunogenicity and safety of a Haemophilus influenzae B (Hib)-hepatitis B vaccine
      with a modified process hepatitis B component administered with concomitant
      pneumococcal conjugate vaccine to infants.
AB  - BACKGROUND: A hepatitis B vaccine was manufactured with a modified process
      (mpHBV) that incorporated double the usual amount of phosphate. Following a study
      in young adults, the mpHBV was evaluated in infants in a combination hepatitis B
      and Haemophilus influenzae B vaccine (mpHBV-Hib). METHODS: The mpHBV-Hib was
      compared with the licensed bivalent HBV-Hib vaccine ComvaxTM for immunogenicity
      and safety. Both vaccines contained 5 MUg/0.5 mL of hepatitis B surface antigen
      (HBsAg) and 7.5 MUg/0.5 mL of PRP-OMPC (polyribosylribitol phosphate outer
      membrane protein complex). A total of 543 infants were randomized 1:1 to receive
      either vaccine at 2, 4 and 12 months of age. A pneumococcal conjugate vaccine
      (PCV) was given concomitantly. Immunogenicity was assessed at 1-month post-dose
      3. RESULTS: Seroprotection rates [% subjects with anti-hepatitis B surface
      antigen antibody titers (anti-HBs) >=10 mIU/mL)] were 100% and 99% for mpHBV-Hib
      and the licensed control (ComvaxTM), respectively. Anti-HBs geometric mean titers
      (GMTs) were 4204 (95% CI, 3411-5182) and 1683 (95% CI, 1350-2099) mIU/mL,
      respectively. Anti-PRP seroprotection rates (SPR) at >=0.15 MUg/mL and at >=1.0
      MUg/mL were 97% and 94%, respectively, for mpHBV-Hib and 96% and 92%,
      respectively, for the control. Anti-PRP GMTs were 7.1 MUg/mL for mpHBV-Hib and
      8.0 MUg/mL for the control. Reactogenicity of the two vaccines was similar.
      CONCLUSIONS: The mpHBV in combination with Hib and with co-administered PCV was
      highly immunogenic. The safety profile of mpHBV-Hib was comparable to the
      licensed control. Both the control and mpHBV-Hib met acceptability criteria for
      seroprotection rates to hepatitis B, with higher anti-HBs GMTs noted for mpHBV
      Hib.

PMID- 21875635
TI  - Predictors of immune response and reactogenicity to AS03B-adjuvanted split virion
      and non-adjuvanted whole virion H1N1 (2009) pandemic influenza vaccines.
AB  - In 2009, 943 children aged 6 months to 10 years were randomised to receive two
      doses of an oil-in water AS03B-adjuvanted split virion or a non-adjuvanted whole
      virion H1N1 (2009) vaccine. The large numbers allowed investigation of possible
      predictors of immune response and reactogenicity. We used regression analysis to
      examine the effect of variables including past receipt of seasonal vaccine,
      antipyretics post-vaccination, interval between doses and pre-existing antibodies
      to H1N1 (2009) on immunogenicity. We also examined the relationship between
      immunogenicity and reactogenicity and whether prior infection or underlying
      conditions affected reactogenicity. For both vaccines, haemagglutination
      inhibition titres were 60% higher in children with fever >=38  degrees C after
      vaccination and 29% lower in those previously given seasonal vaccine. Early use
      of antipyretics did not affect immunogenicity. Post-vaccination titres were
      higher with longer intervals between doses and in those with evidence of prior
      infection, but reactogenicity in the latter was unaffected. In the adjuvanted
      vaccine group, reactions were more common in children with atopy. Both vaccines
      were safe and immunogenic in those with prior infection. Reduction in the
      interval between doses for earlier protection would be at the cost of reduced
      immunogenicity. The effect of seasonal vaccine on immunogenicity merits further
      investigation.

PMID- 21875637
TI  - Identification and immunogenicity of Mannheimia haemolytica S1 outer membrane
      lipoprotein PlpF.
AB  - Immunity against Mannheimia haemolytica requires antibodies against leukotoxin
      (LKT) and bacterial cell surface antigens, most likely immunogenic outer membrane
      proteins (OMPs). Five immunogenic outer membrane lipoproteins identified and
      characterized in M. haemolytica were designated Pasteurella lipoproteins (Plp) A,
      -B, -C, -D and -E. Using immunoproteomics, we identified a heretofore
      uncharacterized M. haemolytica immunogenic outer membrane lipoprotein that we
      designated PlpF, which was previously designated in the published sequence as a
      conserved hypothetical protein. We cloned and expressed rPlpF from two M.
      haemolytica serotype 1 strains (SAC159 and SAC160) and demonstrated a variable
      number of perfect (KKTEED) or imperfect (KKaEEa) repeats between residues 41 and
      76 on the N-terminus. Antigenicity plots predicted the N-terminus repeat region
      to be highly antigenic. The plpF gene in multiple M. haemolytica S1, S2, and S6
      isolates varied in the number of repeats from three to seven. C-terminal region
      was highly conserved. Immunization of mice with SAC159 or SAC160 demonstrated
      immunogenicity in a dose-response manner. Immunization of calves demonstrated an
      increase in antibodies to PlpF, and rPlpF antibodies stimulated complement
      mediated killing of M. haemolytica. Because calves had pre-existing anti-M.
      haemolytica antibodies due to prior natural exposure, functionality of the anti
      PlpF antibody responses were demonstrated by marked reduction of complement
      mediated killing by blocking of anti-PlpF antibodies with rPlpF In conclusion,
      PlpF might have vaccination potential against M. haemolytica infection in cattle.

PMID- 21875636
TI  - Associations between single nucleotide polymorphisms and haplotypes in cytokine
      and cytokine receptor genes and immunity to measles vaccination.
AB  - Identification of host genetic determinants of measles vaccine-induced immunity
      can be used to design better vaccines and ultimately predict immune responses to
      vaccination. We performed a comprehensive candidate gene association study across
      801 genetic markers in 56 cytokine/cytokine receptor genes, in a racially diverse
      cohort of 745 schoolchildren after two doses of MMR vaccine. Using linear
      regression methodologies we examined associations between SNPs/haplotypes and
      measles virus-specific immunity. Forty-eight significant SNP associations with
      variations in neutralizing antibodies and measles-specific IFNgamma Elispot
      responses were identified (p<0.05). Our study replicated an important previously
      found association of a functional IL12B genetic variant rs3212227 with variations
      in measles-specific humoral immunity (p=0.037). Similarly, two previously
      reported promoter IL10 and IL2 polymorphisms (rs1800890 and rs2069762)
      demonstrated associations with measles-specific cellular immunity in Caucasians
      (p<=0.034). Multiple IL7R polymorphisms, including a non-synonymous functional
      SNP (rs6897932/Thr244Ile), were associated with humoral (p<=0.024) and/or
      cellular (IFNgamma Elispot, p<=0.023) measles-specific immune responses in
      Caucasians, but not African-Americans. Haplotype level analysis confirmed the
      association of IL7R genetic variants with measles vaccine-induced immunity in the
      Caucasian group (global p-value=0.003). Our results validate previous findings
      and identify new plausible genetic determinants, including IL7R polymorphisms,
      regulating measles vaccine-induced immunity in a race-specific manner.

PMID- 21875638
TI  - Comparing live attenuated and inactivated hepatitis A vaccines: an immunogenicity
      study after one single dose.
AB  - INTRODUCTION: While three types of hepatitis A vaccines are available in China,
      little data are available to compare them in terms of early antibody response. We
      conducted a trial to compare antibody response at 7, 14 and 28 days. METHODS: We
      randomized primary school children in Gansu and Jilin provinces into four groups
      to receive either (1) Chinese live attenuated hepatitis A vaccine (H2 strain),
      (2) domestic inactivated hepatitis A vaccine (Healive((r))), (3) imported
      inactivated hepatitis A vaccine (Havrix((r))) or (4) hepatitis B vaccine (Control
      group). We compared groups at 7, 14 and 28 days in terms of proportion of sero
      conversions (>=10 mUI/ml), and Geometric Mean Concentration (GMC) of antibodies
      measured with a Microparticle Enzyme Immunoassay (MEIA). We compared rates of
      self-reported adverse events following immunization (AEFI) in the first three
      days. RESULTS: 204 children received the H2 vaccine, 208 received Healive((r)),
      214 received Havrix((r)), and 215 received hepatitis B vaccine (no differences
      across groups in terms of age, sex, weight and height). At seven days, sero
      conversion proportions were 25%, 35%, 27% and 2% (p<0.0001) with GMC of 6 mIU/ml,
      8 mIU/ml, 6 mIU/ml and 3 mIU/ml, respectively for the four groups. At 28 days,
      sero-conversion proportions were 98%, 100%, 93% and 3% (p<0.0001) with GMC of 47
      mIU/ml, 71 mIU/ml, 67 mIU/ml and 3 mIU/ml, respectively. AEFI were benign and did
      not differ across groups (p=0.94). CONCLUSIONS: While our study was not able to
      identify differences between Havrix((r)), Healive((r)) and H2 vaccine in terms of
      sero-conversion proportion and GMC between seven and 28 days, further studies
      should evaluate non-inferiority or equivalence of the Chinese vaccines,
      particularly with respect to the GMC concentration for the H2 vaccine since it
      could affect long-term protection.

PMID- 21875639
TI  - Study parameters influencing NOAEL and LOAEL in toxicity feeding studies for
      pesticides: exposure duration versus dose decrement, dose spacing, group size and
      chemical class.
AB  - The effect of exposure duration on no observed adverse effect levels (NOAEL) and
      lowest observed adverse effect levels (LOAEL) in rodent pesticide feeding studies
      was evaluated. Ratios of NOAEL (and LOAEL), expressed as pesticide concentrations
      in feed, were calculated from subacute to subchronic, subchronic to chronic and
      subacute to chronic studies. There was no statistical significant effect of
      exposure duration on ratio distributions. Whereas geometric means of ratios were
      in a narrow range of 1.1-2.5, the geometric standard deviations and 95th
      percentiles increased with dose spacing of the involved studies. With the
      exception of carbamates, the chemical class of pesticides had no influence on the
      ratio distributions. However, the number of animals in the shorter-term study of
      ratio couples being <= 1 was statistically significantly higher than in ratio
      couples being >1. Ratios <= 1 may be partly explained by the dose decrement over
      time observed in feeding studies applying the test substances in constant
      concentrations. The dose decrement possibly converts initially toxic doses to
      less toxic doses beyond the subacute phase. Ratios >1 seem to be caused
      predominantly by differences in study design parameters. In dietary risk
      assessment, the acceptable daily intake (ADI) is compared to pesticide intake
      estimates based on mean food consumption (i.e. the so called theoretical maximum
      daily intake, TMDI) being orders of magnitude lower than actual food consumption
      on eating occasions for certain food commodities. As subacute, subchronic and
      chronic NOAEL (and LOAEL), expressed as pesticide concentration in feed did not
      differ statistically significantly, the TMDI as benchmark for the ADI may
      underestimate the significance of the toxicity of subacute exposure.

PMID- 21875640
TI  - Effects of a chewing gum containing phosphoryl oligosaccharides of calcium (POs
      Ca) and fluoride on remineralization and crystallization of enamel subsurface
      lesions in situ.
AB  - OBJECTIVES: Manufacturers are adding fluoride (F) to calcium-containing chewing
      gums to further promote enamel remineralization. The aim of this study was to
      assess the effect of a chewing gum containing phosphoryl oligosaccharides of
      calcium (POs-Ca) and fluoride on remineralization of enamel subsurface lesions,
      in a double-blind, randomized controlled in situ trial. METHODS: Thirty-six
      volunteer subjects wore removable buccal appliances with three different insets
      of bovine enamel with subsurface demineralized lesions. For 14 days the subjects
      chewed one of the three chewing gums (placebo, POs-Ca, POs-Ca+F), three times a
      day. After each treatment period, the insets were removed from the appliance,
      embedded, sectioned, polished and then subjected to laboratory tests; mineral
      level was determined by transverse microradiography (TMR; n=36), and
      hydroxyapatite (HAp) crystallites were assessed by synchrotron radiation wide
      angle X-ray diffraction (WAXRD; n=13). Data were analysed by t-test or Wilcoxon
      rank-sum test with Bonferroni corrections at 0.05 significance level. RESULTS:
      Chewing POs-Ca and POs-Ca+F gums resulted in 21.9+/-10.6 and 26.3+/-9.4 (mean+/
      SD) percentage mineral recovery, which was significantly higher than that of
      placebo gum (15.0+/-11.4) (p<0.05). Chewing POs-Ca+F gum resulted in 24.9+/-5.4
      (mean+/-SD) percentage HAp crystallites recovery, which was significantly higher
      compared to POs-Ca (16.0+/-4.1%) or placebo (11.1+/-4.8%) gums (p<0.05).
      CONCLUSIONS: Addition of POs-Ca to the chewing gum resulted in significant
      remineralization of enamel subsurface lesions. Although POs-Ca+F gum was not
      superior in TMR recovery rate when compared with POs-Ca gum, WAXRD results
      highlighted the importance of fluoride ion bioavailability in the formation of
      HAp crystallites in enamel subsurface lesions in situ (NCT01377493).

PMID- 21875641
TI  - Subjective image quality assessment of cross sectional imaging methods for the
      symphyseal region of the mandible prior to dental implant placement.
AB  - OBJECTIVES: A three dimensional appreciation of the form of the anterior mandible
      is required to place dental implants safely in the region. This study compared
      the subjective image quality of four available methods of cross sectional imaging
      of the symphyseal region, the lateral cephalometric view, cone beam computed
      tomography (CBCT), spiral tomography and the transymphyseal X-ray view. METHODS:
      An experimental water phantom was developed to reproduce human soft tissue around
      the mandible. Images were taken of four mandibles by the four X-ray techniques.
      Three different CBCT machines were included. The source of each image was
      disguised by displaying all images in the same format on the same computer
      screen. A protocol was developed to process the images for viewing whilst
      preserving their image quality. A panel of observers of ten dentists viewed the
      images and rated their image quality by recording their agreement with six
      statements on a five point Likert scale. RESULTS: The results showed a
      statistically significant difference in image quality between imaging methods.
      There were clear differences in the ratings between the three cone beam computed
      tomography machines. Small volume, high resolution CBCT provided images with the
      highest scores for subjective image quality. CONCLUSIONS: Within the limitations
      of this study, significant differences in subjective image quality were found
      between imaging systems used for cross sectional imaging for the symphyseal
      region of the mandible prior to dental implant placement.

PMID- 21875642
TI  - Comments on "Inhibition of estrogen actions in human gynecological malignancies:
      new aspects of endocrine therapy for endometrial cancer and ovarian cancer".

PMID- 21875644
TI  - Estrogen biosynthesis and signaling in endometriosis.
AB  - Endometriosis is an estrogen-dependent gynecological disease where endometrium
      like tissue grows outside uterine cavity. Endometriotic cell proliferation is
      stimulated by estrogens acting predominantly via their nuclear receptors.
      Estrogen receptors (ESR1, ESR2) are ligand activated transcription factors whose
      activation is dependent on the cell-specific dynamic expression of the receptors,
      on the interacting proteins and on the ligand availability. The different types
      of endometriotic lesions, peritoneal, deep, and ovarian endometriosis, may
      respond to estrogens differentially due to differences in the expression of the
      receptors and interacting proteins, and due to potential differences in the
      ligand availability regulated by the local estrogen synthesis. This review
      summarizes the current knowledge of estrogen synthesizing enzymes and estrogen
      receptors in different types of endometriosis lesions. Further studies are still
      needed to define the possible differences in steroid metabolism in different
      types of endometriotic lesions.

PMID- 21875645
TI  - Expression and genetic analysis of miRNAs involved in CD4+ cell activation in
      patients with multiple sclerosis.
AB  - MicroRNA (miRNA)-mediate RNA interference has been identified as a novel
      mechanism that regulates protein expression. It is recognised that miRNAs play
      essential roles in the immune system and for correct function in the brain.
      Moreover, it is now clear that abnormal miRNA expression is a common feature of
      several diseases involving the immune system including multiple sclerosis (MS).
      Expression analysis for miR-21, miR-146a and -b, miR-150, miR-155 was carried out
      in peripheral mononuclear cells (PBMC) from a cohort of 29 MS patients and 19
      controls. Subsequently, a case control study for miR-146 rs2910164 variant was
      performed in an overall population of 346 MS cases and 339 controls. A
      statistically significant increased expression of miR-21, miR-146a and -b was
      observed in relapsing remitting (RR)MS patients as compared with controls (1.44+/
      0.13 vs 0.79+/-0.06, P=0.036; 1.50+/-0.12 vs 0.84+/-0.08, P=0.039; 1.54+/-0.15 vs
      0.72+/-0.08, P=0.001 respectively). On the contrary, no differences were found in
      the expression levels of both miR-150 and miR-155 in patients as compared with
      controls (P>0.05). The genetic association study failed to find any differences
      in the frequencies of rs2910164 between patients and controls. miRNA
      dysregulation may contribute to the pathogenesis of MS and highlights the
      possibility to define different disease entities with specific miRNAs profile.

PMID- 21875646
TI  - Parietal and temporal activity during a multimodal dance video game: an fNIRS
      study.
AB  - Using functional near infrared spectroscopy (fNIRS) we studied how playing a
      dance video game employs coordinated activation of sensory-motor integration
      centers of the superior parietal lobe (SPL) and superior temporal gyrus (STG).
      Subjects played a dance video game, in a block design with 30s of activity
      alternating with 30s of rest, while changes in oxy-hemoglobin (oxy-Hb) levels
      were continuously measured. The game was modified to compare difficult (4-arrow),
      simple (2-arrow), and stepping conditions. Oxy-Hb levels were greatest with
      increased task difficulty. The quick-onset, trapezoidal time-course increase in
      SPL oxy-Hb levels reflected the on-off neuronal response of spatial orienting and
      rhythmic motor timing that were required during the activity. Slow-onset, bell
      shaped increases in oxy-Hb levels observed in STG suggested the gradually
      increasing load of directing multisensory information to downstream processing
      centers associated with motor behavior and control. Differences in temporal
      relationships of SPL and STG oxy-Hb concentration levels may reflect the
      functional roles of these brain structures during the task period. NIRS permits
      insights into temporal relationships of cortical hemodynamics during real motor
      tasks.

PMID- 21875647
TI  - Antidepressant-like effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro
      isoquinolin-4-YL)-cyclohexanol, a putative trace amine receptor ligand involves l
      arginine-nitric oxide-cyclic guanosine monophosphate pathway.
AB  - 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)-cyclohexanol is a
      novel putative trace amine receptor modulator hypothesized to be useful for
      treatment-resistant depression. In our previous study, we have demonstrated the
      antidepressant-like effect of this molecule in mouse forced swim and tail
      suspension tests and shown to act via modulating the levels of norepinephrine,
      serotonin and dopamine. The present study attempts to explore the involvement of
      l-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the
      antidepressant-like effect of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro
      isoquinolin-4-YL)-cyclohexanol in the mouse forced swim test. The antidepressant
      like action of 1-(7-methoxy-2-methyl-1,2,3,4-tetrahydro-isoquinolin-4-YL)
      cyclohexanol (8 mg/kg, i.p) was reversed by pretreatment with L-arginine (750
      mg/kg, i.p.), a nitric oxide precursor. In contrast, pretreatment with methylene
      blue (a soluble guanlyate cyclase inhibitor and nitric oxide synthase (NOS)
      inhibitor) or 7-nitroindazole (a specific neuronal NOS inhibitor) potentiated the
      antidepressant-like effect of sub-effective dose of 1-(7-methoxy-2-methyl-1,2,3,4
      tetrahydro-isoquinolin-4-YL)-cyclohexanol (2mg/kg, i.p.) in this test model.
      Furthermore, the antidepressant-like effect of this molecule (8 mg/kg, i.p.) was
      reversed by sildenafil (5mg/kg, i.p.), a phosphodiesterase inhibitor. In
      conclusion, the antidepressant-like action of 1-(7-methoxy-2-methyl-1,2,3,4
      tetrahydro-isoquinolin-4-YL)-cyclohexanol involved L-arginine-nitric oxide-cyclic
      guanosine monophospate signaling pathway.

PMID- 21875648
TI  - Enhanced motor cortex facilitation in patients with vascular cognitive impairment
      no dementia.
AB  - Data on Transcranial Magnetic Stimulation (TMS) derived measures of cortical
      excitability and intracortical circuits in age-related white matter changes are
      scarce. We aimed to assess early changes of motor cortex excitability in
      nondemented elderly patients with subcortical ischemic vascular disease (SVD).
      Ten SVD elderly and ten age-matched controls underwent paired-pulse TMS for the
      analysis of intracortical inhibition (ICI) and facilitation (ICF). All subjects
      performed neuropsychological assessment and brain magnetic resonance imaging. SVD
      patients showed abnormal executive control function. No statistically significant
      differences were found for resting motor threshold, cortical silent period
      between SVD patients and controls or between the two hemispheres, in patients. A
      significant enhancement of mean ICF was observed in SVD patients. This study
      provides the first evidence of functional changes in intracortical excitatory
      neuronal circuits in patients with SVD and clinical features of vascular
      cognitive impairment-no dementia. Further studies are required to evaluate
      whether the observed change of ICF might predict cognitive and/or motor
      impairment in a population at risk for subcortical vascular dementia.

PMID- 21875650
TI  - The antimicrobial peptide arenicin-1 promotes generation of reactive oxygen
      species and induction of apoptosis.
AB  - BACKGROUND: Arenicin-1, a 21-residue antimicrobial peptide, is known to exert
      significant broad-spectrum antimicrobial activity without cytotoxicity in
      mammalian cells except at high concentration. However, the mechanism of fungal
      cell death by arenicin-1 is weakly understood. METHODS: We confirmed an increase
      in reactive oxygen species (ROS) in Candida albicans exposed to arenicin-1 and
      investigated the apoptotic response to ROS accumulation using apoptosis detecting
      methods. RESULTS AND CONCLUSIONS: Cells exposed to arenicin-1 showed an increase
      in the production of ROS and cytotoxic hydroxyl radicals, which are the major
      factors of apoptosis. The increase in ROS was due to mitochondrial dysfunction
      caused by arenicin-1. We confirmed that arenicin-1 induced mitochondrial membrane
      depolarization and also triggered release of activated metacaspases. Further, it
      initiated an apoptotic mechanism acting on the plasma membrane, including plasma
      membrane depolarization and exposure of phosphatidylserine on the outer surface.
      Cells finally died, showing morphological changes in the nucleus and DNA
      structure. Based on these apoptotic phenomena induced by arenicin-1, we concluded
      that arenicin-1 exerts antifungal activity by inducing apoptosis. GENERAL
      SIGNIFICANCE: This study suggests that the antimicrobial peptide arenicin-1
      induces apoptosis in C. albicans via intracellular ROS accumulation and
      mitochondrial damage, resulting in fungal cell death.

PMID- 21875649
TI  - Stroke treatment in rats with tail temperature increase by 40-min moxibustion.
AB  - The distant heat induced by suspended moxibustion (SM) for 40 min is confirmed to
      have a favorable effect in treating diseases such as ischemic brain injury in the
      clinical setting, but its precise mechanism remains to be explained. Since a
      similar reaction to the phenomenon of distant heat is found in some transient
      middle cerebral artery occlusion (tMCAO) rats treated by a 40-min SM session with
      tail temperature increase (TTI), we hereby study its mechanism by comparing the
      neuroprotective effect of 40 min's SM with TTI to those without. The experimental
      results show that 40 min's SM with TTI can significantly reduce the infarct
      volume and neurological deficit score in tMCAO rats. Western blot demonstrates
      that a reduction in the levels of cyclooxygenase-2 (COX-2), inducible nitric
      oxide synthase (iNOS) expression in tMCAO rats with TTI is more striking than
      that of the rats without TTI. The expression of caspase-3 protein is inhibited in
      tMCAO rats with TTI. The results suggest that the efficacy of SM for 40 min with
      TTI is higher than that without. Although neuroprotective effects present in
      tMCAO rats with and without TTI, those with TTI revealed a higher level of anti
      inflammation effect and exhibited an anti-apoptosis effect.

PMID- 21875651
TI  - Cytoarchitectural disruption of the superior colliculus and an enlarged acoustic
      startle response in the Tuba1a mutant mouse.
AB  - The Jenna mutant mouse harbours an S140G mutation in Tuba1a that impairs tubulin
      heterodimer formation resulting in defective neuronal migration during
      development. The consequence of decreased neuronal motility is a fractured
      pyramidal cell layer in the hippocampus and wave-like perturbations in the
      cerebral cortex. Here, we extend our characterisation of this mouse investigating
      the laminar architecture of the superior colliculus (SC). Our results reveal that
      the structure of the SC in mutant animals is intact; however, it is significantly
      thinner with an apparent fusion of the intermediate grey and white layers.
      Birthdate labelling at E12.5 and E13.5 showed that the S140G mutation impairs the
      radial migration of neurons in the SC. A quantitative assessment of neuronal
      number in adulthood reveals a massive reduction in postmitotic neurons in mutant
      animals, which we attribute to increased apoptotic cell death. Consistent with
      the role of the SC in modulating sensorimotor gating, and the circuitry that
      modulates this behaviour, we find that Jenna mutants exhibit an exaggerated
      acoustic startle response. Our results highlight the importance of Tuba1a for
      correct neuronal migration and implicate postnatal apoptotic cell death in the
      pathophysiological mechanisms underlying the tubulinopathies.

PMID- 21875653
TI  - Impaired social interaction and enhanced sensitivity to phencyclidine-induced
      deficits in novel object recognition in rats with cortical cholinergic
      denervation.
AB  - Dysregulated cholinergic neurotransmission has been implicated in the
      pathophysiology of schizophrenia, particularly negative symptoms and cognitive
      deficits. The aim of the present study was to evaluate the role of neocortical
      cholinergic innervation and of the N-methyl-d-aspartate (NMDA) receptor
      antagonist phencyclidine (PCP) on social interaction and novel object recognition
      (NOR), a declarative memory task. The cholinergic corticopetal projection was
      lesioned by local infusion of the immunotoxin 192 IgG-saporin into nucleus
      basalis magnocellularis of adult male Lister hooded rats. Behavior was assessed
      2.5 weeks later in a social interaction paradigm followed by the NOR task. We
      found that selective cholinergic denervation of neocortex led to a significant
      reduction in duration of social interaction, specifically active social
      interaction. Acute administration of PCP (1.0 mg/kg, s.c.) caused a marked
      decrease of active social interaction, such that there was no longer a difference
      between intact and denervated animals. Neither cholinergic denervation alone, nor
      PCP (1.0 mg/kg, s.c.) alone blocked the ability of rats to recognize a novel
      object. However, when animals lacking cortical cholinergic innervation were
      challenged by PCP, they were no longer able to recognize a novel object. This
      study indicates that rats lacking cholinergic innervation of neocortex have
      impaired social interaction and specifically that the duration of active contact
      is shortened. Animals with severe cortical cholinergic hypofunction maintain the
      ability to perform in a declarative memory test, although the task is carried out
      less intensively. However, a provocation of psychosis-like behavior by a dose of
      PCP that does not by itself impair performance in normal animals, will abolish
      the ability to recognize novel objects in animals lacking cortical cholinergic
      innervation. The present findings support a possible role for cortical
      cholinergic hypofunction in the negative and cognitive symptoms of schizophrenia,
      and the potential for cholinergic augmentation as part of the pharmacological
      profile of antipsychotic drugs.

PMID- 21875652
TI  - Testosterone and social isolation influence adult neurogenesis in the dentate
      gyrus of male rats.
AB  - Testosterone has been previously shown to enhance adult neurogenesis within the
      dentate gyrus of adult male rats, whereas social isolation has been shown to
      cause a decrease in adult neurogenesis under some conditions. The current study
      tested the combined effects of testosterone and social isolation upon adult
      neurogenesis using two experiments involving adult male rats. For both
      experiments, half of the subjects were pair-housed and half were housed
      individually for the duration of the experiments (34 days). For experiment 1, the
      subjects were divided into four groups (n=8/group): (1) sham/pair-housed, (2)
      sham/isolated, (3) castrate/pair-housed, and (4) castrate/isolated. Rats in the
      castrate groups were bilaterally castrated, and rats in the sham groups were sham
      castrated. For experiment 2, all rats were castrated, and the effects of
      testosterone were tested using daily injections of testosterone propionate (0.500
      mg/rat for 15 days) or the oil vehicle. Subjects were divided into four groups
      (n=8/group): (1) oil/pair-housed, (2) oil/isolated, (3) testosterone/pair-housed,
      and (4) testosterone/isolated. All rats were injected with 5-bromo-2'
      deoxyuridine (BrdU, 200 mg/kg body mass), and immunohistochemistry was used to
      determine levels of neurogenesis following a 16-day cell survival period. For
      experiment 1, castrated subjects had significantly fewer BrdU-labeled cells along
      the granule cell layer and subgranular zone (GCL+SGZ) of the dentate gyrus than
      did intact subjects, and this effect was mainly due to low levels of neurogenesis
      in the castrate/isolated group. For experiment 2, social isolation caused a
      significant decrease in neurogenesis within the GCL+SGZ relative to the pair
      housed groups. Testosterone injections did not buffer against this effect but
      instead tended to cause a decrease in neurogenesis. Thus, social isolation
      reduced hippocampal neurogenesis, but the effects of testosterone were
      inconsistent. This suggests that normal circulating levels of testosterone may
      buffer against the neurogenesis-impairing effects of isolation, whereas high
      doses of testosterone do not.

PMID- 21875654
TI  - Neuronal localization of M2 muscarinic receptor immunoreactivity in the rat
      amygdala.
AB  - Muscarinic cholinergic neurotransmission in the amygdala is critical for memory
      consolidation in emotional/motivational learning tasks, but little is known about
      the neuronal distribution of different receptor subtypes. Immunohistochemistry
      was used in the present investigation to localize the m2 receptor (M2R).
      Differential patterns of M2R-immunoreactivity (M2R-ir) were observed in the
      somata and neuropil of the various amygdalar nuclei. Neuropilar M2R-ir was
      strongest in rostral portions of the basolateral nuclear complex (BLC). M2R
      positive (M2R+) somata were seen in low numbers in all nuclei of the amygdala.
      Most M2R+ neurons associated with the BLC were in the lateral nucleus and
      external capsule. These cells were nonpyramidal neurons that contained glutamatic
      acid decarboxylase (GAD), somatostatin (SOM), and neuropeptide Y (NPY), but not
      parvalbumin (PV), calretinin (CR), or cholecystokinin (CCK). Little or no M2R-ir
      was observed in GAD+, PV+, CR+, or CCK+ axons in the BLC, but it was seen in some
      SOM+ axons and many NPY+ axons. M2R-ir was found in a small number of spiny and
      aspiny neurons of the central nucleus that were mainly located along the lateral
      and ventral borders of its lateral subdivision. Many of these cells contained SOM
      and NPY. M2R+ neurons were also seen in the medial nucleus, including a distinct
      subpopulation of neurons that surrounded its anteroventral subdivision. The
      latter neurons were negative for all neuronal markers analyzed. The intercalated
      nuclei (INs) were associated with two types of large M2R+ neurons, spiny and
      aspiny. The small principal neurons of the INs were M2R-negative. The somata and
      dendrites of the large spiny neurons, which were actually found in a zone located
      just outside of the rostral INs, expressed SOM and NPY, but not GAD. These
      findings indicate that acetylcholine can modulate a variety of discrete neuronal
      subpopulations in various amygdalar nuclei via M2Rs, especially neurons that
      express SOM and NPY.

PMID- 21875655
TI  - Brn-3b inhibits generation of amacrine cells by binding to and negatively
      regulating DLX1/2 in developing retina.
AB  - During retinogenesis, the basic helix-loop-helix proneural gene math5 (atoh7)
      initiates the generation of the first-born neurons, retinal ganglion cells
      (RGCs), by activating a network of RGC transcription factors, including Brn-3b
      (POU4F2). Herein, we show that the expression of DLX1 and DLX2 is significantly
      down-regulated in math5-null retina but is markedly increased in Brn-3b-null
      retina. Interestingly, Brn-3b interacts with DLX1 through its homeodomain, and
      this interaction represses DLX1 activity. Retrovirus-mediated mis-expression of
      DLX1 or DLX2 dramatically increases the number of amacrine/bipolar cells and
      concurrently reduces rod photoreceptors. Conversely, combined ectopic expression
      of Brn-3b with DLX1 or DLX2 promotes the production of RGCs and inhibits amacrine
      cell differentiation. Thus, DLX1/2 play an essential role in cell fate selection
      between amacrine and RGCs. Brn-3b suppresses the role of DLX1/2 through physical
      interaction and biases the competent precursors toward RGC fates.

PMID- 21875656
TI  - Mimicking maternal smoking and pharmacotherapy of preterm labor: fetal nicotine
      exposure enhances the effect of late gestational dexamethasone treatment on
      noradrenergic circuits.
AB  - Smoking during pregnancy increases the risk of preterm delivery, which in turn
      necessitates the common use of glucocorticoids to prevent respiratory distress
      syndrome. Accordingly, there is a substantial population exposed conjointly to
      fetal nicotine and glucocorticoids (typically dexamethasone). We administered
      nicotine to pregnant rats throughout gestation, using a regimen (3 mg/kg/day by
      osmotic minipump) that maintains plasma nicotine levels within the range seen in
      smokers; on gestational days 17, 18 and 19, we gave 0.2 mg/kg of dexamethasone.
      We assessed norepinephrine levels in three brain regions (frontal/parietal
      cortex, brainstem, cerebellum) throughout adolescence, young adulthood and later
      adulthood, and contrasted the persistent effects with comparable measures in
      peripheral tissues (heart, liver). In adolescence, males showed initial deficits
      in the frontal/parietal cortex with either dexamethasone alone or the combined
      treatment, with resolution to normal by young adulthood; the group exposed to
      both nicotine+dexamethasone showed subsequent elevations that emerged in full
      adulthood and persisted through five months of age, an effect not seen with
      either agent separately. In females, the combined exposure produced an initial
      deficit that resolved by young adulthood, without any late-emerging changes. We
      did not see comparable effects in the other brain regions or peripheral tissues.
      This indicates that nicotine exposure sensitizes the developing brain to the
      adverse effects of dexamethasone treatment, producing sex-selective changes in
      innervation and/or activity of specific noradrenergic circuits. The fact that the
      combined treatment produced greater effects points to potentially worsened
      neurobehavioral outcomes after pharmacotherapy of preterm labor in the offspring
      of smokers.

PMID- 21875657
TI  - Assessment of PCBs exposure in human hair using double focusing high resolution
      mass spectrometry and single quadrupole mass spectrometry.
AB  - Polychlorinated biphenyls (PCBs) levels were assessed in human hair samples,
      originating from two main agricultural regions of Greece. The analysis was
      performed by gas chromatography-mass spectrometry (GC-MS) and gas chromatography
      double focusing high resolution mass spectrometry (GC-DFHRMS). The main
      analytical procedure involved hair decontamination, solid-liquid extraction and
      cleanup steps. The recoveries of PCBs ranged from 71.2% to 101.6%, with
      accuracies greater than 87.5% and the between-run precisions (%RSD) lower than
      25% for all analytes. Differences in the frequencies of detection and the median
      values of PCBs were detected between the examined regions and between the applied
      analytical techniques. All Peloponnesus' hair examined samples were found
      positive for each examined PCB, while the percentage of the total positive
      samples ranged from 86.1% (for PCB 138) to 94.4% (for PCB 28 and 153 congeners)
      using GC-DFHRMS. The Cretan hair samples were less contaminated (SUM PCBs=0.61
      and 1.47pg/mg) unlike the Peloponnesus' samples (SUM PCBs=24.68 and 38.74pg/mg)
      measured by GC-DFHRMS and GC-MS, respectively. PCBs with high chlorination gave
      lower concentration values compared to low chlorination PCBs in both populations.
      No significant differences were observed between women and men. The GC-DFHRMS
      technique provided higher percentage of positive samples and low PCBs median
      values, due to higher sensitivity and interferences from isobaric ions in the GC
      MS technique and is therefore considered as a powerful tool for such assessments
      in hair specimens.

PMID- 21875660
TI  - Comparison on the anti-inflammatory effect of Cortex Phellodendri Chinensis and
      Cortex Phellodendri Amurensis in 12-O-tetradecanoyl-phorbol-13-acetate-induced
      ear edema in mice.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Cortex Phellodendri is derived from the dried
      bark of Phellodendron chinense Schneid. or Phellodendron amurense Rupr.
      Traditionally, Cortex Phellodendron Chinensis (CPC) and Cortex Phellodendron
      Amurensis (CPA) are used interchangeably under the name "Huang Bai" for the
      treatment of gastroenteritis, abdominal pain or diarrhea. The present study aims
      to compare the anti-inflammatory effect of ethanol extracts of Cortex
      Phellodendri Chinensis (ECPC) and Cortex Phellodendri Amurensis (ECPA) in a mouse
      model of inflammation induced by 12-O-tetradecanoylphorbol-acetate (TPA).
      MATERIALS AND METHODS: The anti-inflammatory effect was evaluated by measuring
      the ear thickness, activity of myeloperoxidase (MPO) and the production reactive
      oxygen species (ROS). The anti-inflammatory mechanism was explored by determining
      the protein and mRNA levels of cyclooxygenase-2 (COX-2), tumor necrosis factor
      alpha (TNF-alpha), interleukin (IL)-1beta and IL-6. RESULTS: The results showed
      that both ECPC and ECPA significantly decreased the ear thickness, MPO activity
      and the ROS level in mouse model of inflammation induced by TPA. In addition,
      ECPC and ECPA also remarkably inhibited the protein and mRNA levels of TNF-alpha,
      IL-1beta, IL-6 and COX-2. Interestingly, ECPC has better anti-inflammatory effect
      than that of ECPA. CONCLUSIONS: These results indicate that both ECPC and ECPA
      have potential anti-inflammatory effect on TPA-induced inflammatory in mice, and
      ECPC is more effective than ECPA. The anti-inflammatory effect of the herbal
      drugs may be mediated, at least in part, by down-regulating the mRNA expression
      of a panel of inflammatory mediators including TNF-alpha, IL-1beta, IL-6 and COX
      2.

PMID- 21875659
TI  - Mature middle and inner ears express Chd7 and exhibit distinctive pathologies in
      a mouse model of CHARGE syndrome.
AB  - Heterozygous mutations in the gene encoding chromodomain-DNA-binding-protein 7
      (CHD7) cause CHARGE syndrome, a multiple anomaly condition which includes
      vestibular dysfunction and hearing loss. Mice with heterozygous Chd7 mutations
      exhibit semicircular canal dysgenesis and abnormal inner ear neurogenesis, and
      are an excellent model of CHARGE syndrome. Here we characterized Chd7 expression
      in mature middle and inner ears, analyzed morphological features of mutant ears
      and tested whether Chd7 mutant mice have altered responses to noise exposure and
      correlated those responses to inner and middle ear structure. We found that Chd7
      is highly expressed in mature inner and outer hair cells, spiral ganglion
      neurons, vestibular sensory epithelia and middle ear ossicles. There were no
      obvious defects in individual hair cell morphology by prestin immunostaining or
      scanning electron microscopy, and cochlear innervation appeared normal in
      Chd7(Gt)(/+) mice. Hearing thresholds by auditory brainstem response (ABR)
      testing were elevated at 4 and 16 kHz in Chd7(Gt)(/+) mice, and there were
      reduced distortion product otoacoustic emissions (DPOAE). Exposure of
      Chd7(Gt)(/+) mice to broadband noise resulted in variable degrees of hair cell
      loss which inversely correlated with severity of stapedial defects. The degrees
      of hair cell loss and threshold shifts after noise exposure were more severe in
      wild type mice than in mutants. Together, these data indicate that Chd7(Gt)(/+)
      mice have combined conductive and sensorineural hearing loss, correlating with
      changes in both middle and inner ears.

PMID- 21875661
TI  - Cortex Mori Radicis extract exerts antiasthmatic effects via enhancement of
      CD4(+)CD25(+)Foxp3(+) regulatory T cells and inhibition of Th2 cytokines in a
      mouse asthma model.
AB  - ETHONOPHARMACOLOGICAL RELEVANCE: Cortex Mori Radicis (CMR), the root epidermis of
      Morus alba L., has been traditionally used for cough treatment in Oriental
      medicine. In the present study, immunological mechanism of CMR in inhibition of
      airway hyperresponsiveness (AHR) was investigated in a mouse asthma model.
      MATERIALS AND METHODS: Experimental asthma model was established in Balb/c mice
      sensitized by ovalbumin (OVA), followed by aerosol allergen challenges. CMR (50
      or 200mg/kg) was orally administered for 6-weeks from 3-weeks after OVA
      sensitization. AHR, pulmonary eosinophilic accumulation, immunoglobulin E (IgE),
      histamine, Th2 cytokine expression, and CD4(+)CD25(+)Foxp3(+) regulatory T cells
      (Tregs) were evaluated by flow cytometry, enzyme-linked immunosorbent assay
      (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS:
      CMR significantly reduced AHR response, eosinophil infiltration, and production
      of serum histamine and OVA-specific IgE. Furthermore, CMR suppressed Th2
      cytokines such as interleukin (IL)-4, -5 and -13 at protein (secreted) and mRNA
      levels. Of note, CMR significantly increased Foxp3(+) Tregs population and
      enhanced Foxp3(+) mRNA expression in a mouse asthma model. CONCLUSIONS: CMR
      exerts anti-allergic effect via enhancement of CD4(+)CD25(+)Foxp3(+) regulatory T
      cells and inhibition of Th2 cytokines in a mouse asthma model as a potent anti
      asthmatic agent.

PMID- 21875662
TI  - Cyptoporus polysaccharide prevents lipopolysaccharide-induced acute lung injury
      associated with down-regulating Toll-like receptor 2 expression.
AB  - AIM OF THE STUDY: To evaluate the effects and the possible mechanism of
      Cryptoporus polysaccharides (CP) extracted from fruiting body of Cryptoporus
      volvatus in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats and
      mice. MATERIALS AND METHODS: Acute lung injury was induced by intratracheally
      instillation of LPS into lung in either rats or mice, assessing leukocyte numbers
      and myeloperoxidase activity in bronchoalveolar lavage fluid, as well as
      evaluating cytokines mRNA and protein expressions, and Toll-like receptor 2
      (TLR(2)) and nuclear factor (NF)-kappaB mRNA levels in the lung tissues of mice.
      Vascular permeability and edema of lung in mice, and arterial blood gas in rats
      were also performed. RESULTS: In ALI, CP-treated mice and rats exhibited
      significantly reduced leukocyte invasion, myeloperoxidase activity, vascular
      permeability, edema of lung, as well as tumor necrosis factor-alpha and
      Interleukin-1beta mRNA and protein expressions in the lung tissues compared with
      vehicle-treated mice. TLR(2) and NF-kappaB mRNA levels of the lung tissues were
      decreased in CP-treated mice in response to LPS. And decline in arterial blood
      gas was recovered in CP-treated rats. CONCLUSIONS: Our results supported a
      protective role of CP in ALI and suggested that the reduction of the activation
      of TLR(2) and NF-kappaB signal pathway in lung injury may be relavant to the
      pretreatment of CP.

PMID- 21875658
TI  - Physiopathology of the cochlear microcirculation.
AB  - Normal blood supply to the cochlea is critically important for establishing the
      endocochlear potential and sustaining production of endolymph. Abnormal cochlear
      microcirculation has long been considered an etiologic factor in noise-induced
      hearing loss, age-related hearing loss (presbycusis), sudden hearing loss or
      vestibular function, and Meniere's disease. Knowledge of the mechanisms
      underlying the pathophysiology of cochlear microcirculation is of fundamental
      clinical importance. A better understanding of cochlear blood flow (CoBF) will
      enable more effective management of hearing disorders resulting from aberrant
      blood flow. This review focuses on recent discoveries and findings related to the
      physiopathology of the cochlear microvasculature.

PMID- 21875663
TI  - Assessment of genotoxic effects of (4-methoxyphenyl)(3,4,5
      trimethoxyphenyl)methanone in human lymphocytes.
AB  - (4-Methoxyphenyl)(3,4,5-trimethoxyphenyl)methanone (PHT) belongs to the
      phenstatin family. This compound has been studied due to its potent cytotoxicity
      and ability to inhibit tubulin assembly. The present study aimed to evaluate the
      mutagenic potential of PHT in human lymphocytes. PHT displayed cytotoxicity in
      human lymphocytes with an IC50 value of 5.68 MUM, and therefore, concentrations
      of 0.25, 0.5, 1.0, 2.0, and 4.0 MUM were used for all protocols. The alkaline
      comet assay and chromosome aberration (CA) analysis were performed in different
      phases of the cell cycle (G1, G1/S, transition, and G2), to evaluate the DNA
      damaging and clastogenic effects of PHT, respectively. CA analysis was carried
      out in the presence or absence of colchicine to evaluate the action of PHT in the
      mitotic phase. PHT was cytotoxic and significantly reduced the mitotic index with
      drug exposure in all phases of cell cycle. Interestingly, it induced an increase
      in mitotic index in experimental protocols without colchicine, corroborating its
      action as an antitubulin agent. It also induced DNA damage and was clastogenic
      with drug exposure in all phases of the cell cycle, in the presence or absence of
      colchicine. In conclusion, PHT induces DNA damage and exerts clastogenic effects
      in human lymphocytes.

PMID- 21875664
TI  - Hydrogen sulfide promotes calcium signals and migration in tumor-derived
      endothelial cells.
AB  - Hydrogen sulfide (H(2)S) is a gasotransmitter that plays several roles in various
      tissues, including the cardiovascular system. Because it has been recently
      proposed to act as a mediator of angiogenesis progression, here we investigate
      the effects of H(2)S in a well-established model of tumor angiogenesis:
      endothelial cells obtained from human breast carcinoma (B-TECs). Ca(2+) imaging
      and patch-clamp experiments reveal that acute perfusion with NaHS, a widely
      employed H(2)S donor, activates cytosolic calcium (Ca(c)) increase, as well as
      potassium and nonselective cationic currents, in B-TECs. Stimulation with NaHS in
      the same concentration range (1 nM-200 MUM) evoked Ca(c) signals also in "normal"
      human microvascular endothelial cells (HMVECs), but the amplitude was
      significantly lower. Moreover, although NaHS failed to promote either migration
      or proliferation on HMVECs, B-TEC migration was enhanced at low-micromolar NaHS
      concentrations (1-10 MUM). Remarkably H(2)S mediates tumor proangiogenic
      signaling triggered by vascular endothelial growth factor (VEGF). B-TECs
      pretreated with dl-propargylglycine (5mM, 30 min), an inhibitor of the H(2)S
      producing enzyme cystathionine gamma-lyase, showed drastically reduced migration
      and Ca(c) signals induced by VEGF (20 ng/ml). We conclude that H(2)S plays a role
      in proangiogenic signaling of tumor-derived but not normal human ECs. Furthermore
      the ability of this gasotransmitter to interfere with B-TEC responsiveness to
      VEGF suggests that it could be an interesting target for antiangiogenic
      strategies in tumor treatment.

PMID- 21875665
TI  - Diphenylarsinic acid produces behavioral effects in mice relevant to symptoms
      observed in citizens who ingested polluted well water.
AB  - Citizens in an area of Kamisu City, Ibaraki, Japan had exhibited unusual health
      problems, and pollution of well water by diphenylarsinic acid (DPAA) was found in
      the area. We examined the effects of DPAA on various behaviors in mice. DPAA was
      administered to mice through free intake of drinking water for 27 weeks
      (subchronic exposure) or 57 weeks (chronic exposure), and behavior was examined
      during exposure. DPAA at 30-100 ppm increased ambulatory activity and the
      response rate of the shuttle type discrete conditioned avoidance response of
      mice. DPAA reduced coordination ability on the fixed rod at 100 ppm. DPAA at 7.5
      15 ppm also reduced coordination on the rotating rod, although these doses of
      DPAA did not affect coordination on the fixed rod. Chronic exposure to 7.5-15 ppm
      of DPAA produced anti-anxiety-like effects in the elevated plus maze test,
      whereas subchronic exposure to 100 ppm of DPAA produced anxiogenic-like effects.
      Neither subchronic nor chronic exposure to 7.5-100 ppm of DPAA affected learning
      ability and/or memory, as evaluated using the passive avoidance response.
      Exposure to 15-30 ppm of DPAA for 52 weeks did not alter weights of the cerebrum
      and cerebellum or amounts of neuron marker protein TUJ-1 or astrocyte marker
      protein glial fibrillary acidic protein in the cerebellum of mice. Behavioral
      effects observed in mice seem relevant to symptoms observed in patients from
      Kamisu City.

PMID- 21875666
TI  - Corticosteroid-binding globulin reactive centre loop antibodies recognise only
      the intact natured protein: elastase cleaved and uncleaved CBG may coexist in
      circulation.
AB  - Corticosteroid-binding globulin (CBG) is the principal carrier of cortisol in
      circulation and is a non-inhibitory member of the serpin family of serine
      proteinase inhibitors. It possesses an exposed elastase specific site which, when
      cleaved, allows a conformational change promoting the delivery of cortisol to
      sites of inflammation. Previously there was no ability to independently
      distinguish between the uncleaved, stressed, conformer of CBG and total CBG in
      circulation. Here we raised and characterized monoclonal antibodies generated
      against a synthetic peptide spanning the elastase cleavage site within the
      exposed reactive centre loop (RCL) and measured changes in CBG by ELISA following
      treatment with human neutrophil elastase. The antibodies recognized the synthetic
      peptide as well as intact CBG and the epitope (STGVTLNL) spanned the elastase
      cleavage site. Treatment of plasma with elastase resulted in a complete loss of
      CBG levels determined using these RCL antibodies whereas CBG levels measured with
      an unrelated CBG monoclonal antibody were unaffected. We also compared plasma
      levels of CBG measured by RCL antibodies and an unrelated CBG antibody and showed
      discordance in some samples. This study shows for the first time the ability to
      measure the intact, stressed conformer of CBG. We report discordance with total
      CBG in some samples implying the presence of cleaved CBG in circulation. This is
      an important finding as it has implications for free cortisol which hitherto have
      been determined from total cortisol and total CBG levels. This antibody could be
      used for determining the time course of intact CBG in various relevant patient
      cohorts and for structure/function studies on the biology of human CBG.

PMID- 21875667
TI  - Biphasic regulation of the acute MU-withdrawal and CCk-8 contracture responses by
      the ORL-1 system in guinea pig ileum.
AB  - The cloning of the opioid-receptor-like receptor (ORL-1) and the identification
      of the orphaninFQ/nociceptin (OFQ/N) as its endogenous agonist has revealed a new
      G-protein-coupled receptor signalling system. The structural and functional
      homology of ORL-1 to the opioid receptor systems has posed a number of challenges
      in the understanding the often competing physiological responses elicited by
      these G-protein-coupled receptors. We had previously shown that in guinea pig
      ileum (GPI), the acute MU-withdrawal response is under the inhibitory control of
      several systems. Specifically, we found that the exposure to a MU-opioid receptor
      agonist activates indirectly the kappa-opioid, the A(1)-adenosine and the
      cannabinoid CB(1) systems, that in turn inhibit the withdrawal response. The
      indirect activation of these systems is prevented by the peptide cholecystokinin
      8 (CCk-8). In the present study, we have investigated whether the ORL-1 system is
      also involved in the regulation of the acute MU-withdrawal response.
      Interestingly, we found that in GPI preparation, the ORL-1 system is not
      indirectly activated by the MU-opioid receptor stimulation, but instead the
      system is able by itself to directly regulate the acute MU-withdrawal response.
      Moreover, we have demonstrated that the ORL-1 system behaves both as anti-opioid
      or opioid-like system based on the level of activation. The same behaviour has
      also been observed in presence of CCk-8. Furthermore, in GPI, the existence of an
      endogenous tone of the ORL-1 system has been demonstrated. We concluded that the
      ORL-1 system acts as a neuromodulatory system, whose action is strictly related
      to the modulation of excitatory neurotrasmitters released in GPI enteric nervous
      system.

PMID- 21875668
TI  - GSK3beta inhibition is involved in the neuroprotective effects of cyclin
      dependent kinase inhibitors in neurons.
AB  - In the present study, we evaluated the effects of roscovitine (Rosco) and
      flavopiridol (Flavo), both of which are classified as cyclin-dependent kinase
      (CDK) inhibitors, on apoptosis induced by the inhibition of PI3K/AKT pathway in
      cerebellar granule neurons (CGNs). Our results demonstrate that both CDK
      inhibitors prevented apoptosis induced by LY294002 (LY), as also occurs with
      SB415286 (SB4), a selective GSK3beta inhibitor. Our findings also indicate that
      these CDK inhibitors inhibit GSK3beta, representing a potential pharmacological
      mechanism involved in their neuroprotective properties. Thus, the increased
      activity of GSK3beta induced by LY294002 and detected by dephosphorylation at
      Ser9 was prevented by both compounds. Likewise, GSK3beta activity was measured by
      a radioactivity assay, revealing that CDK inhibitors and SB415286 prevented the
      increase in GSK3beta activity induced by PI3K inhibition. In addition, we
      analysed c-Jun, which is also a mediator of PI3K inhibition-induced apoptosis.
      However, neither of the CDK inhibitors nor SB415286 prevented the increase in c
      Jun phosphorylation induced by PI3K inhibition. Therefore, our data identify
      GSK3beta as a crucial mediator of CGN apoptosis induced by PI3K inhibition and
      indicate that the antiapoptotic effects of CDKs are mediated by the inhibition of
      this pharmacological target.

PMID- 21875669
TI  - swap70 promotes neural precursor cell cycle exit and oligodendrocyte formation.
AB  - Multipotent neural precursors produce oligodendrocyte lineage cells, which then
      migrate throughout the central nervous system and extend multiple, long membrane
      processes to wrap and myelinate axons. These dynamic cellular behaviors imply
      dynamic regulation of the cytoskeleton. In a previous microarray screen for new
      oligodendrocyte genes we identified swap70, which encodes a protein with domains
      that predict numerous signaling activities. Because mouse Swap70 can promote cell
      motility by functioning as a guanine nucleotide exchange factor for Rac1, we
      hypothesized that zebrafish Swap70 promotes oligodendrocyte progenitor cell (OPC)
      motility and axon wrapping. To test this we investigated Swap70 localization in
      OPCs and differentiating oligodendrocytes and we performed a series of gain and
      loss of function experiments. Our tests of gene function did not provide evidence
      that Swap70 regulates oligodendrocyte lineage cell behavior. Instead, we found
      that swap70 deficient larvae had excess neural precursors and a deficit of OPCs.
      Cells associated with neural proliferative zones express swap70. Therefore, our
      data reveal a potential new role for Swap70 in regulating transition of dividing
      neural precursors to specified OPCs.

PMID- 21875670
TI  - Expression, purification, and initial structural characterization of
      nonstructural protein 2B, an integral membrane protein of Dengue-2 virus, in
      detergent micelles.
AB  - Dengue virus causes serious diseases affecting people in tropical and sub
      tropical regions. The nonstructural (NS) protein 2B is an integral membrane
      protein and important for the regulation of viral protease NS3, which is
      significant for virus replication. The NS2B-NS3 complex is an important drug
      target for treating dengue fever. However, little is known about the structure of
      NS2B in its entirety. Herein, we describe the expression and purification of this
      integral membrane protein from cell membrane and inclusion bodies of Escherichia
      coli cells. The initial nuclear magnetic resonance (NMR) and circular dichroism
      (CD) results indicate that the purified protein adopts alpha-helical structures
      in LMPG and TDPC micelles.

PMID- 21875671
TI  - Measuring structural-functional correspondence: spatial variability of
      specialised brain regions after macro-anatomical alignment.
AB  - The central question of the relationship between structure and function in the
      human brain is still not well understood. In order to investigate this
      fundamental relationship we create functional probabilistic maps from a large set
      of mapping experiments and compare the location of functionally localised regions
      across subjects using different whole-brain alignment schemes. To avoid the major
      problems associated with meta-analysis approaches, all subjects are scanned using
      the same paradigms, the same scanner and the same analysis pipeline. We show that
      an advanced, curvature driven cortex based alignment (CBA) scheme largely removes
      macro-anatomical variability across subjects. Remaining variability in the
      observed spatial location of functional regions, thus, reflects the "true"
      functional variability, i.e. the quantified variability is a good estimator of
      the underlying structural-functional correspondence. After localising 13 widely
      studied functional areas, we found a large variability in the degree to which
      functional areas respect macro-anatomical boundaries across the cortex. Some
      areas, such as the frontal eye fields (FEF) are strongly bound to a macro
      anatomical location. Fusiform face area (FFA) on the other hand, varies in its
      location along the length of the fusiform gyrus even though the gyri themselves
      are well aligned across subjects. Language areas were found to vary greatly
      across subjects whilst a high degree of overlap was observed in sensory and motor
      areas. The observed differences in functional variability for different
      specialised areas suggest that a more complete estimation of the structure
      function relationship across the whole cortex requires further empirical studies
      with an expanded test battery.

PMID- 21875672
TI  - Optimization of functional brain ROIs via maximization of consistency of
      structural connectivity profiles.
AB  - Segregation and integration are two general principles of the brain's functional
      architecture. Therefore, brain network analysis is of significant importance in
      understanding brain function. Critical to brain network construction and analysis
      is the identification of reliable, reproducible, and accurate network nodes, or
      Regions of Interest (ROIs). Task-based fMRI has been widely considered as a
      reliable approach to identify functionally meaningful ROIs in the brain. However,
      recent studies have shown that factors such as spatial smoothing could
      considerably shift the locations of detected activation peaks. As a result,
      structural and functional connectivity patterns can be significantly altered.
      Here, we propose a novel framework by which to optimize ROI sizes and locations,
      ensuring that differences between the structural connectivity profiles among a
      group of subjects is minimized. This framework is based on functional ROIs
      derived from task-based fMRI and diffusion tensor imaging (DTI) data.
      Accordingly, we present a new approach to describe and measure the fiber bundle
      similarity quantitatively within and across subjects which will facilitate the
      optimization procedure. Experimental results demonstrated that this framework
      improved the localizations of fMRI-derived ROIs. Through our optimization
      procedure, structural and functional connectivities were more consistent across
      different individuals. Overall, the ability to accurately localize network ROIs
      could facilitate many applications in brain imaging that rely on the accurate
      identification of ROIs.

PMID- 21875673
TI  - Automatic identification of gray and white matter components in polarized light
      imaging.
AB  - Polarized light imaging (PLI) enables the visualization of fiber tracts with high
      spatial resolution in microtome sections of postmortem brains. Vectors of the
      fiber orientation defined by inclination and direction angles can directly be
      derived from the optical signals employed by PLI analysis. The polarization state
      of light propagating through a rotating polarimeter is varied in such a way that
      the detected signal of each spatial unit describes a sinusoidal signal. Noise,
      light scatter and filter inhomogeneities, however, interfere with the original
      sinusoidal PLI signals, which in turn have direct impact on the accuracy of
      subsequent fiber tracking. Recently we showed that the primary sinusoidal signals
      can effectively be restored after noise and artifact rejection utilizing
      independent component analysis (ICA). In particular, regions with weak
      intensities are greatly enhanced after ICA based artifact rejection and signal
      restoration. Here, we propose a user independent way of identifying the
      components of interest after decomposition; i.e., components that are related to
      gray and white matter. Depending on the size of the postmortem brain and the
      section thickness, the number of independent component maps can easily be in the
      range of a few ten thousand components for one brain. Therefore, we developed an
      automatic and, more importantly, user independent way of extracting the signal of
      interest. The automatic identification of gray and white matter components is
      based on the evaluation of the statistical properties of the so-called feature
      vectors of each individual component map, which, in the ideal case, shows a
      sinusoidal waveform. Our method enables large-scale analysis (i.e., the analysis
      of thousands of whole brain sections) of nerve fiber orientations in the human
      brain using polarized light imaging.

PMID- 21875675
TI  - From joint anatomy to clinical outcomes in osteoarthritis and cartilage repair:
      summary of the fifth annual osteoarthritis imaging workshop.
AB  - OBJECTIVE: This white paper constitutes an overview of presentations and
      discussions from the fifth Annual Workshop on Imaging in Osteoarthritis (OA) held
      in Salzburg June eighth to eleventh 2011. DESIGN: This workshop brought together
      the communities of basic OA researchers, orthopedists and rheumatologists,
      imaging scientists, instrument manufacturers, and pharmaceutical representatives
      to focus on three overlapping themes of joint anatomy, cartilage repair and
      clinical validation of imaging biomarkers. RESULTS: The workshop was held on the
      campus of the Paracelsus Medical University in Salzburg, Austria from June 8-11,
      2011; 133 attendees participated, representing 17 countries. The meeting was
      successful in facilitating discussion, raising awareness and consolidating
      knowledge about application of imaging in OA research studies and cartilage
      repair. CONCLUSIONS: The OA research communities need to work alongside the
      regulatory, pharmaceutical, and MRI industries to support the new ideas and
      engage in the positive reinforcement of resources to further the new studies. A
      number of new initiatives were discussed to further break down obstacles to
      clinical trial utility of imaging biomarkers.

PMID- 21875676
TI  - Prevalence of symptomatic hip and knee osteoarthritis: a two-phase population
      based survey.
AB  - OBJECTIVE: Osteoarthritis (OA) epidemiologic data are scarce in Europe. To
      estimate the prevalence of symptomatic knee and hip OA in a multiregional sample
      in France. DESIGN: A two-phase population-based survey was conducted in six
      regions in 2007-2009. On initial phone contact using random-digit dialing,
      subjects 40-75 years old were screened with a validated questionnaire. Subjects
      screened positive were invited for ascertainment: physical examination and hip
      and/or knee radiography (Kellgren-Lawrence grade>=2). Multiple imputation for
      data missing not-at-random was used to account for refusals. RESULTS: Of 63,232
      homes contacted, 27,632 were eligible, 9621 subjects screened positive, 3707
      participated fully in the ascertainment phase, and 1010 had symptomatic OA: 317
      hip, 756 knee. Hip OA prevalence according to age class ranged from 0.9% to 3.9%
      for men and 0.7-5.1% for women. Knee OA ranged from 2.1% to 10.1% for men and 1.6
      14.9% for women. Both differed by geographical region. The hip and knee
      standardized prevalence was 1.9% and 4.7% for men and 2.5% and 6.6% for women,
      respectively. CONCLUSIONS: This confirmed the feasibility of using a screening
      questionnaire for eliciting population-based estimates of OA. In France, it
      increases with age and is greater among women above the age of 50. The
      geographical disparity of hip and knee OA parallels the distribution of obesity.
      Study registration ID number 906297 at http://www.clinicaltrials.gov/.

PMID- 21875674
TI  - Cardiorespiratory fitness is positively correlated with cerebral white matter
      integrity in healthy seniors.
AB  - High cardiorespiratory fitness (CRF) is an important protective factor reducing
      the risk of cardiac-related disability and mortality. Recent research suggests
      that high CRF also has protective effects on the brain's macrostructure and
      functional response. However, little is known about the potential relationship
      between CRF and the brain's white matter (WM) microstructure. This study explored
      the relationship between a comprehensive measure of CRF (VO(2) peak, total time
      on treadmill, and 1-minute heart rate recovery) and multiple diffusion tensor
      imaging measures of WM integrity. Participants were 26 healthy community dwelling
      seniors between the ages of 60 and 69 (mean=64.79 years, SD=2.8). Results
      indicated a positive correlation between comprehensive CRF and fractional
      anisotropy (FA) in a large portion of the corpus callosum. Both VO(2) peak and
      total time on treadmill contributed significantly to explaining the variance in
      mean FA in this region. The CRF-FA relationship observed in the corpus callosum
      was primarily characterized by a negative correlation between CRF and radial
      diffusivity in the absence of CRF correlations with either axial diffusivity or
      mean diffusivity. Tractography results demonstrated that portions of the corpus
      callosum associated with CRF primarily involved those interconnecting frontal
      regions associated with high-level motor planning. These results suggest that
      high CRF may attenuate age-related myelin declines in portions of the corpus
      callosum that interconnect homologous premotor cortex regions involved in motor
      planning.

PMID- 21875677
TI  - Coronal plane ankle alignment, gait, and end-stage ankle osteoarthritis.
AB  - OBJECTIVE: Unilateral ankle osteoarthritis (OA) is a debilitating condition which
      may lead to limb deformity, severe pain, and functional disability due to
      tibiotalar malalignment and gait dysfunction. The purpose of this study was to
      determine if coronal plane alignment (varus, valgus, or neutral) of the ankle
      resulted in different spatial-temporal gait mechanics, clinically-assessed
      function, and self-reported function in patients with end-stage ankle OA.
      METHODS: Following informed consent, 96 patients with end-stage unilateral ankle
      OA were radiographically categorized as having varus, valgus, or neutral
      tibiotalar alignment. Each subject completed the foot and ankle disability index
      (FADI) questionnaire to assess self-reported function. The spatial-temporal
      parameters of interest (stance time, step length, stride length, stride width,
      single-support time, double support time, and walking speed) were assessed while
      the subject walked at a self-selected speed. RESULTS: The varus group performed
      the timed up and go test significantly faster than the other groups (P=0.05). All
      other variables were similar between the three alignment groups. CONCLUSION:
      There was little difference in gait mechanics and function between patients with
      end-stage OA based on coronal plane ankle alignment suggesting that factors other
      than coronal plane alignment contribute to diminished function.

PMID- 21875678
TI  - Efficacy evaluation of highly purified intra-articular hyaluronic acid
      (Sinovial((r))) vs hylan G-F20 (Synvisc((r))) in the treatment of symptomatic
      knee osteoarthritis. A double-blind, controlled, randomized, parallel-group non
      inferiority study.
AB  - OBJECTIVE: Knee osteoarthritis is a major cause of disability and pain. This
      phase III, double-blind (patient and observer blinded,) multicenter, randomized,
      non-inferiority study was conducted to demonstrate the non-inferiority of the
      highly purified intra-articular injection of hyaluronic acid (Sinovial((r))) in
      comparison to Hylan G-F20 (Synvisc((r))) in the treatment of knee osteoarthritis.
      METHODS: A total of 381 patients were randomly assigned to receive either the
      test drug, 16 mg/2 ml (0.8%) highly purified ia hyaluronic acid of
      biofermentative origin (Sinovial((r))), or the comparative drug, 16 mg/2 ml of
      0.8% hylan G-F20 (Synvisc((r))). The duration of the treatment was 2 weeks (three
      injections at 1-week interval), followed by an observation period of 6 months.
      The primary efficacy variable was the improvement in mean Western Ontario and
      McMaster Universities (WOMAC) pain subscore from baseline to the final visit
      (week 26), compared between the two treatment groups. The acceptable margin for
      non-inferiority was chosen to be 8 mm. RESULTS: At week 26, WOMAC pain subscores
      decreased by a mean of 32.5 for both Sinovial((r)) and Synvisc((r)). These
      results met prespecified criteria for non-inferiority for both the Intent-to
      Treat and Per-Protocol populations. There were no statistically significant
      differences between groups at 26 weeks, although Sinovial((r))-treated patients
      tended to have a slightly better outcome for select variables, as they did at
      earlier time-points, some of which reached statistical significance. Both
      hyaluronic acid preparations were well-tolerated, with no statistically
      significant differences in tolerability profile between groups. CONCLUSION:
      Sinovial((r)) and Synvisc((r)) treatments were found to be equivalent, both in
      terms of efficacy and safety. CLINICAL TRIAL NUMBER: NCT00556608
      (ClinicalTrials.gov Identifier).

PMID- 21875680
TI  - In vitro and in vivo antioxidant activity of exopolysaccharide fractions from
      Bifidobacterium animalis RH.
AB  - The aim of the study was to purify the exopolysaccharides (EPS) produced from
      Bifidobacterium animalis RH, which was isolated from the feces of Bama
      centenarians in Guangxi of China, and evaluate their antioxidant activities in
      vitro and in vivo. 2 fractions, a neutral EPS fraction (EPSa) and an acidic EPS
      fraction (EPSb), were obtained and compared for antioxidative activity. In vitro,
      they both showed remarkable inhibition effect on lipid peroxidation and strong
      DPPH radical scavenging activity, hydroxyl radical scavenging activity,
      superoxide radical scavenging activity, in which the last two were measured by
      the electron spin resonance (ESR). In vivo, EPSa and EPSb were orally
      administrated for 30 days in a d-galactose induced aged mice model. As results,
      they both could significantly increase the activities of SOD, CAT and total
      antioxidant capacity (TAOC) in serums and glutathione GST in livers. They also
      could inhibit significantly the formation of MDA in serums and livers, and reduce
      the activity of MAO and lipofuscin accumulation in mice brain. Moreover, EPSb
      exhibited much higher antioxidant activities than EPSa in vitro and in vivo. The
      results suggested that EPS fractions of Bifidobacterium animalis RH had direct
      and potent antioxidant activities.

PMID- 21875681
TI  - The neuronal NO synthase participation in the peripheral antinociception
      mechanism induced by several analgesic drugs.
AB  - The production of nitric oxide (NO) from l-arginine is catalyzed by NO synthase
      (NOS), which exists as the following three isoforms: endothelial (eNOS), neuronal
      (nNOS), and inducible (iNOS). The participation of this pathway in peripheral
      antinociception has been extensively established by our group with the use of
      several types of drugs, including opioids, cannabinoids, cholinergic, and
      alpha(2C) adrenoceptor agonists and nonsteroidal anti-inflammatory drugs
      (NSAIDS), and even non-pharmacological procedures such as electroacupuncture. In
      this study, we aimed to refine the previous data to investigate which type of NOS
      isoform is involved in the peripheral antinociception mechanism induced by
      anandamide, morphine, SNC80, bremazocine, acetylcholine, xylazine, baclofen,
      dipyrone, and diclofenac. After hyperalgesia was induced by intraplantar
      injection of prostaglandin E(2) in male Wistar rats, we measured peripheral
      nociception with the paw pressure test. All drugs that were used induced a
      peripheral antinociception effect that was completely blocked by injection of the
      selective neuronal NO synthase inhibitor, L-NPA (24MUg/paw). The exception was
      the GABA(B) agonist baclofen, which induced an effect that was not antagonized.
      We used the inhibitors L-NIO and -NIL (24MUg/paw) to exclude the involvement of
      endothelial and inducible NO synthase, respectively. These drugs were ineffective
      against the antinociception effect induced by all analgesic drugs that we
      utilized. Based on the experimental evidence, we conclude that the local
      injection of analgesic drugs activates nNOS to release NO and induce peripheral
      antinociception.

PMID- 21875682
TI  - Anti-VEGF and beyond: shaping a new generation of anti-angiogenic therapies for
      cancer.
AB  - The anti-angiogenic class of drugs is one of the few where representatives have
      gained international approval for clinical use in oncology during the past
      decade. Most of the biological and clinical activity of the currently available
      generation of anti-angiogenic drugs targets vascular endothelial growth factor
      (VEGF) and its related pathways. However, the clinical benefits associated with
      the use of these drugs have, so far, been limited. There is, therefore, an unmet
      need for biomarkers that can be used to identify patients who are most likely to
      benefit therapeutically and also to predict the best schedule and dosage for
      these drugs. Here, we discuss some of the emerging new combination strategies
      involving the approved anti-angiogenic drugs, some of the emerging targets
      associated with neoplastic angiogenesis and some novel agents used as a paradigm
      of the next generation of anti-angiogenic drugs.

PMID- 21875683
TI  - Pharmacogenetics: practices and opportunities for study design and data analysis.
AB  - Pharmacogenetics (PGx) is increasingly used as a way to target treatment to
      patients who are most likely to benefit. To date, PGx has shown clinical
      significance across a few applications but widespread use has been limited by the
      need for further technical, methodological and practical advances and for
      educating clinical researchers on the value of PGx. Here, I describe the current
      scope of PGx research, including recent contributions to prospective study
      design. A case study is included to demonstrate the limitations of current
      practice and to describe some practical steps for improving the chances of
      identifying genetic effects. Additionally, I describe some opportunities for the
      integration and application of disparate data sources in exploratory PGx
      research.

PMID- 21875679
TI  - The cognitive cost of sleep lost.
AB  - A substantial body of literature supports the intuitive notion that a good
      night's sleep can facilitate human cognitive performance the next day. Deficits
      in attention, learning & memory, emotional reactivity, and higher-order cognitive
      processes, such as executive function and decision making, have all been
      documented following sleep disruption in humans. Thus, whilst numerous clinical
      and experimental studies link human sleep disturbance to cognitive deficits,
      attempts to develop valid and reliable rodent models of these phenomena are
      fewer, and relatively more recent. This review focuses primarily on the cognitive
      impairments produced by sleep disruption in rodent models of several human
      patterns of sleep loss/sleep disturbance. Though not an exclusive list, this
      review will focus on four specific types of sleep disturbance: total sleep
      deprivation, experimental sleep fragmentation, selective REM sleep deprivation,
      and chronic sleep restriction. The use of rodent models can provide greater
      opportunities to understand the neurobiological changes underlying sleep loss
      induced cognitive impairments. Thus, this review concludes with a description of
      recent neurobiological findings concerning the neuroplastic changes and putative
      brain mechanisms that may underlie the cognitive deficits produced by sleep
      disturbances.

PMID- 21875684
TI  - Harnessing opportunities in non-animal asthma research for a 21st-century
      science.
AB  - The incidence of asthma is on the increase and calls for research are growing,
      yet asthma is a disease that scientists are still trying to come to grips with.
      Asthma research has relied heavily on animal use; however, in light of
      increasingly robust in vitro and computational models and the need to more fully
      incorporate the 'Three Rs' principles of Replacement, Reduction and Refinement,
      is it time to reassess the asthma research paradigm? Progress in non-animal
      research techniques is reaching a level where commitment and integration are
      necessary. Many scientists believe that progress in this field rests on linking
      disciplines to make research directly translatable from the bench to the clinic;
      a '21st-century' scientific approach to address age-old questions.

PMID- 21875685
TI  - Morphometric and molecular characterization of Gyrodactylus teuchis Lautraite,
      Blanc, Thiery, Daniel & Vigneulle, 1999 (Monogenea: Gyrodactylidae) from an
      Austrian brown trout population.
AB  - Gyrodactylus teuchis is a widespread parasite of wild and farmed salmonids
      throughout Europe. It has been frequently confused with the notifiable pathogen
      G. salaris, to which it bears a striking morphological similarity. The species is
      frequently referred to as 'cryptic', and diagnoses are primarily based on
      molecular evidence. We provide the first comprehensive re-description of G.
      teuchis from a natural wild brown trout population in the Danube watershed, based
      on the state of the art morphometrics in addition to standard molecular markers.
      We demonstrate that despite the lack of uni-variate diagnostic character
      measurements, G. teuchis can be reliably distinguished from G. salaris using
      multivariate morphological approaches such as Principal Component Analysis or
      Canonical Variate Analysis, suggesting that automated diagnostic approaches for
      G. salaris can be modified to take account of potential G. teuchis in samples.
      This is the first record of G. teuchis from a host population unlikely to have
      been modified by human stocking efforts. The morphological variability observed
      in the samples collected from one site on 1 day reflects the overall level of
      variation reported for European G. teuchis. We also report new sequence variants
      of the internal transcribed spacer (ITS-1) of the nuclear ribosomal gene cluster
      with evidence for intra-individual heterogeneity of ITS-1 within this population
      of G. teuchis.

PMID- 21875686
TI  - Increased risk of coronary artery disease in Caucasians with extremely low HDL
      cholesterol due to mutations in ABCA1, APOA1, and LCAT.
AB  - Mutations in ABCA1, APOA1, and LCAT reduce HDL cholesterol (HDLc) in humans.
      However, the prevalence of these mutations and their relative effects on HDLc
      reduction and risk of coronary artery disease (CAD) are less clear. Here we
      searched for ABCA1, APOA1, and LCAT mutations in 178 unrelated probands with HDLc
      <10th percentile but no other major lipid abnormalities, including 89 with >=1
      first-degree relative with low HDLc (familial probands) and 89 where familial
      status of low HDLc is uncertain (unknown probands). Mutations were most frequent
      in LCAT (15.7%), followed by ABCA1 (9.0%) and APOA1 (4.5%), and were found in
      42.7% of familial but only 14.6% of unknown probands (p=2.44*10(-5)).
      Interestingly, only 16 of 24 (66.7%) mutations assessed in families conferred an
      average HDLc <10th percentile. Furthermore, only mutation carriers with HDLc <5th
      percentile had elevated risk of CAD (odds ratio (OR)=2.26 for 34 ABCA1 mutation
      carriers vs. 149 total first-degree relative controls, p=0.05; OR=2.50 for 26
      APOA1 mutation carriers, p=0.04; OR=3.44 for 38 LCAT mutation carriers, p=1.1*10(
      3)). These observations show that mutations in ABCA1, APOA1, and LCAT are
      sufficient to explain >40% of familial hypoalphalipoproteinemia in this cohort.
      Moreover, individuals with mutations and large reductions in HDLc have increased
      risk of CAD. This article is part of a Special Issue entitled Advances in High
      Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945
      2010).

PMID- 21875687
TI  - Tight association of N-terminal and catalytic subunits of rabbit 12/15
      lipoxygenase is important for protein stability and catalytic activity.
AB  - 12/15-Lipoxygenases (12/15-LOXs) have been implicated in inflammatory and
      hyperproliferative diseases but the structural biology of these enzymes is not
      well developed. Most LOXs constitute single polypeptide chain proteins that fold
      into a two-domain structure. In the crystal structure the two domains are tightly
      associated, but small angle X-ray scattering data and dynamic fluorescence
      studies suggested a high degree of structural flexibility involving movement of
      the N-terminal domain relative to catalytic subunit. When we inspected the
      interdomain interface we have found a limited number of side-chain contacts which
      are involved in interactions of these two structural subunits. One of such
      contact points involves tyrosine 98 of N-terminal domain. This aromatic amino
      acid is invariant in vertebrate LOXs regardless of overall sequence identity. To
      explore in more detail the role of aromatic interactions in interdomain
      association we have mutated Y98 to various residues and quantified the structural
      and functional consequences of these alterations. We have found that loss of an
      aromatic moiety at position 98 impaired the catalytic activity and membrane
      binding capacity of the mutant enzymes. Although CD and fluorescence emission
      spectra of wild-type and mutant enzyme species were indistinguishable, the
      mutation led to enlargement of the molecular shape of the enzyme as detected by
      analytic gel filtration and this structural alteration was shown to be associated
      with a loss of protein thermal stability. The possible role of tight interdomain
      association for the enzyme's structural performance is discussed.

PMID- 21875688
TI  - Quantification of endocannabinoids in biological systems by chromatography and
      mass spectrometry: a comprehensive review from an analytical and biological
      perspective.
AB  - The endocannabinoids anandamide (arachidonoyl ethanolamide, AEA) and 2
      arachidonoyl glycerol (2AG) are physiologically occurring, biologically active
      compounds on CB(1) and CB(2) receptors with multiple physiological functions. AEA
      and 2AG have been identified and quantified in many mammalian biological fluids
      and tissues, such as human plasma, adipocytes, tissues and tissue
      microdialysates, at concentrations in the picomolar-to-nanomolar range under
      basal conditions. In this article, recently published chromatographic and mass
      spectrometric analytical methods, i.e., HPLC with fluorescence or ultraviolet
      detection, LC-MS, LC-MS/MS, GC-MS and GC-MS/MS, are reviewed and discussed,
      notably from the quantitative point of view. We focus on and emphasize the
      particular importance of blood sampling, sample storage and work-up including
      solvent and solid-phase extraction and derivatization procedures, matrix-effects,
      and stability of analytes. As 2AG spontaneously isomerizes to its CB(1)/CB(2)
      receptors biologically inactive 1-arachidonoyl glycerol (1AG) by acyl migration,
      this phenomenon and its particular importance for accurate quantification of 2AG
      are discussed in detail. Due to the electrical neutrality of AEA and 2AG their
      solvent extraction by toluene offers the least matrix-effect and minimum
      isomerization. LC-MS/MS is the most frequently used analytical technique for AEA
      and 2AG. At present, the utility of the GC-MS/MS methodology seems to be limited
      to AEA measurement in human plasma, bronchoalveolar liquid (BAL) and
      microdialysate samples. Despite great instrumental advances in the LC-MS/MS
      methodology, sampling and sample treatment remains one of the most crucial
      analytical steps in 2AG analysis. Extension of the LC-MS/MS methodology, for
      instance to microdialysate and BAL samples from clinical studies, is a big
      analytical challenge in endocannabinoid analysis in clinical settings. Currently
      available LC-MS/MS and GC-MS/MS methods should be useful to investigate the
      metabolism of AEA and 2AG beyond hydrolysis, i.e., by beta- and omega-oxidation
      pathways.

PMID- 21875689
TI  - Synthetic LXR agonist inhibits the development of atherosclerosis in New Zealand
      White rabbits.
AB  - The nuclear receptors Liver X receptors, LXRalpha and LXRbeta, regulate
      cholesterol and triglyceride metabolism. We and others have previously reported
      that synthetic LXR agonists reduced atherosclerosis in models of mouse with no
      detectable plasma cholesteryl ester transfer protein (CETP) activity, which plays
      an important role in reverse cholesterol transport. In the present study, we
      investigated the effect of LXR activation in rabbits to elucidate the influence
      of CETP activity. First, we cloned rabbit LXRs cDNA. The data indicated that
      rabbit LXRalpha was mostly highly expressed in the liver, whereas LXRbeta
      expression was ubiquitous. Next, we investigated the effect of LXR agonist on
      lipid levels. Treatment with LXR agonist T0901317 increased plasma CETP activity
      and consequently elevated LDL, but no change in HDL. High cholesterol (HC) diet
      feeding, which is thought to provide oxysterols as the natural agonists, could
      also increase expression of CETP and other LXR target genes. Finally, we tested
      T0901317 in the atherosclerosis intervention study. Chronic administration of
      T0901317 significantly reduced atherosclerosis in HC diet-fed rabbits despite
      less favorable lipid profiles, i.e. increases of plasma triglycerides and no
      change of HDL. T0901317 induced ATP-binding cassette transporters ABCA1 and ABCG1
      and suppressed inflammatory genes expression in the aorta, suggesting that direct
      actions of LXR agonist on vascular gene expression are likely to contribute to
      the antiatherogenic effect. The present work strongly supports the idea that LXR
      agonists could be beneficial as therapeutic agents for treatment of
      atherosclerosis.

PMID- 21875690
TI  - Metabolic link between phosphatidylethanolamine and triacylglycerol metabolism in
      the yeast Saccharomyces cerevisiae.
AB  - In the yeast Saccharomyces cerevisiae triacylglycerols (TAG) are synthesized by
      the acyl-CoA dependent acyltransferases Dga1p, Are1p, Are2p and the acyl-CoA
      independent phospholipid:diacylglycerol acyltransferase (PDAT) Lro1p which uses
      phosphatidylethanolamine (PE) as a preferred acyl donor. In the present study we
      investigated a possible link between TAG and PE metabolism by analyzing the
      contribution of the four different PE biosynthetic pathways to TAG formation,
      namely de novo PE synthesis via Psd1p and Psd2p, the CDP-ethanolamine (CDP-Etn)
      pathway and lyso-PE acylation by Ale1p. In cells grown on the non-fermentable
      carbon source lactate supplemented with 5mM ethanolamine (Etn) the CDP-Etn
      pathway contributed most to the cellular TAG level, whereas mutations in the
      other pathways displayed only minor effects. In cki1?dpl1?eki1? mutants bearing
      defects in the CDP-Etn pathway both the cellular and the microsomal levels of PE
      were markedly decreased, whereas in other mutants of PE biosynthetic routes
      depletion of this aminoglycerophospholipid was less pronounced in microsomes.
      This observation is important because Lro1p similar to the enzymes of the CDP-Etn
      pathway is a component of the ER. We conclude from these results that in
      cki1?dpl1?eki1? insufficient supply of PE to the PDAT Lro1p was a major reason
      for the strongly reduced TAG level. Moreover, we found that Lro1p activity was
      markedly decreased in cki1?dpl1?eki1?, although transcription of LRO1 was not
      affected. Our findings imply that (i) TAG and PE syntheses in the yeast are
      tightly linked; and (ii) TAG formation by the PDAT Lro1p strongly depends on PE
      synthesis through the CDP-Etn pathway. Moreover, it is very likely that local
      availability of PE in microsomes is crucial for TAG synthesis through the Lro1p
      reaction.

PMID- 21875692
TI  - Immunomodulation by chemotherapeutic agents against Leishmaniasis.
AB  - Leishmaniasis is caused by protozoan parasites of the genus Leishmania and causes
      a wide spectrum of clinical manifestations ranging from self-healing cutaneous
      lesions to the fatal visceral form. The use of pentavalent antimony, the mainstay
      of therapy of Leishmaniasis is now limited by its toxicity and alarming increase
      in unresponsiveness, especially in the Indian subcontinent. Furthermore, other
      anti-leishmanial drugs are unaffordable in many affected countries and as
      vaccination based approaches have not yet proved to be effective, chemotherapy
      remains the only alternative, emphasizing the need for identifying novel drug
      targets. In this review, we have described the different host immune signaling
      pathways that could be considered as potential drug targets for Leishmania
      chemotherapy.

PMID- 21875691
TI  - "Bird biting" mosquitoes and human disease: a review of the role of Culex pipiens
      complex mosquitoes in epidemiology.
AB  - The transmission of vector-borne pathogens is greatly influenced by the ecology
      of their vector, which is in turn shaped by genetic ancestry, the environment,
      and the hosts that are fed on. One group of vectors, the mosquitoes in the Culex
      pipiens complex, play key roles in the transmission of a range of pathogens
      including several viruses such as West Nile and St. Louis encephalitis viruses,
      avian malaria (Plasmodium spp.), and filarial worms. The Cx. pipiens complex
      includes Culex pipiens pipiens with two forms, pipiens and molestus, Culex
      pipiens pallens, Culex quinquefasciatus, Culex australicus, and Culex
      globocoxitus. While several members of the complex have limited geographic
      distributions, Cx. pipienspipiens and Cx. quinquefasciatus are found in all known
      urban and sub-urban temperate and tropical regions, respectively, across the
      world, where they are often principal disease vectors. In addition, hybrids are
      common in areas of overlap. Although gaps in our knowledge still remain, the
      advent of genetic tools has greatly enhanced our understanding of the history of
      speciation, domestication, dispersal, and hybridization. We review the taxonomy,
      genetics, evolution, behavior, and ecology of members of the Cx. pipiens complex
      and their role in the transmission of medically important pathogens. The
      adaptation of Cx. pipiens complex mosquitoes to human-altered environments led to
      their global distribution through dispersal via humans and, combined with their
      mixed feeding patterns on birds and mammals (including humans), increased the
      transmission of several avian pathogens to humans. We highlight several
      unanswered questions that will increase our ability to control diseases
      transmitted by these mosquitoes.

PMID- 21875693
TI  - MitoBamAnnotator: A web-based tool for detecting and annotating heteroplasmy in
      human mitochondrial DNA sequences.
AB  - The use of Next-Generation Sequencing of mitochondrial DNA is becoming widespread
      in biological and clinical research. This, in turn, creates a need for a
      convenient tool that detects and analyzes heteroplasmy. Here we present
      MitoBamAnnotator, a user friendly web-based tool that allows maximum flexibility
      and control in heteroplasmy research. MitoBamAnnotator provides the user with a
      comprehensively annotated overview of mitochondrial genetic variation, allowing
      for an in-depth analysis with no prior knowledge in programming.

PMID- 21875694
TI  - Critical co-stimulatory pathways in the stability of Foxp3+ Treg cell homeostasis
      in Type I diabetes.
AB  - Mechanisms of peripheral tolerance maintain a controlled balance between self
      tolerance, protective immunity against a spectrum of non-self antigens, and
      suppressing pathology in various disorders. CD4(+) regulatory T cells (T(reg))
      expressing the Foxp3 transcription factor dominantly control the activity and
      pathological consequences of a variety of effector T cell lineages in various
      inflammatory settings. This review will focus on recent advances on the roles of
      B7 family members in regulating Treg cell development, function and homeostasis
      during tolerance induction and organ-specific autoimmunity.

PMID- 21875695
TI  - Charged residues on a flap-loop structure of Lactococcus lactis prolidase play
      critical roles in allosteric behavior and substrate inhibition.
AB  - Allosteric behavior and substrate inhibition are unique characteristics of
      Lactococcus lactis prolidase. We hypothesized that charged residues (Asp36,
      His38, Glu39, and Arg40), present on one loop essential for catalysis, interact
      with residues in or near the active site to impart these unique characteristics.
      Asp36 has a predominant role in the allosteric behavior, as demonstrated through
      the non-allosteric behavior of the D36S mutant enzyme. In contrast, a double
      mutant (D36E/R293K) maintained the allostery, indicating that this aspartic acid
      residue interacts with Arg293, previously shown to be critical in the allostery.
      Substitution of His38 drastically reduced the substrate inhibition, and substrate
      specificity of the mutant at Asp36 or His38 showed the influence of these
      residues to the substrate specificity. These findings confirm the importance of
      the loop in the enzymatic reaction mechanism and suggest the existence of
      conformational changes of the loop structure between open and closed states. A
      variety of mutations at Glu39 and Arg40 showed that these residues influence
      roles of the loop in the enzyme reaction. On the basis of these results and
      combined with observations of molecular models of this prolidase, we concluded
      that Asp36 and His38 interact with the residues in the active site to generate an
      allosteric subsite and a pseudo-S(1)' site, which are responsible for the
      allosteric behavior and substrate inhibition.

PMID- 21875696
TI  - A retrospective study examining thrombolysis for occluded femoro-popliteal grafts
      - is it worthwhile?
AB  - AIM: To assess the effectiveness of catheter directed thrombolysis (CDT) in the
      treatment of acute graft occlusion. METHODS: Tissue prothrombin activator (rt-PA)
      was the sole agent used for thrombolysis. This was infused through a 4F straight
      65 cm catheter placed under ultrasound guidance. Following a pre-CDT angiogram, a
      catheter was placed just proximal to the distal anastomosis. An infusion of rt-PA
      was given over 24 h. An assessment of acute clinical success, limb salvage rates,
      patency rates and complication rates were made over a period of one year.
      RESULTS: 80% (20/25) of grafts were successfully reopened immediately. 4/5 (80%)
      of the unsuccessful CDT cases required amputation within a few weeks. 60% (12/20)
      of successful CDT cases had an underlying stenotic lesion which required
      angioplasty. Limb salvage rate was 72% (18/25) at 12 months. There was no CDT
      related mortality. Secondary patency rate at 9 months was 76% (13/17).
      CONCLUSION: CDT can achieve reasonable results in this group of challenging
      patients and may be seen as a useful accessory in the vascular toolkit. However,
      precise indications for its use need further clarification.

PMID- 21875697
TI  - Dye assisted lymphatic sparing subinguinal varicocelectomy. A prospective
      randomized study.
AB  - BACKGROUND: Division of lymphatic vessels during varicocelectomy could lead to
      hydrocele formation and decrease in testicular function due to testicular edema.
      We determined if the use of methylene blue combined with optical magnification
      reduces the incidence of post-varicocelectomy hydrocele. METHODS: Consecutive
      patients treated for varicocele at our institution were evaluated for inclusion.
      Participants were randomly allocated to receive either subinguinal
      varicocelectomy after 2 ml intratunical space injection of methylene blue and
      group 2 in whom no mapping technique was adopted during subinguinal
      varicocelectomy. After surgery, the patients were assessed at 2 weeks, 6 and 12
      months for hydrocele, testicular edema, varicocele recurrence, atrophy, pain or
      other complications with mean follow-up was 15 +/- 7 months. RESULTS: Eighty
      patients with varicocele were randomized and completed the study. There were no
      intra complications in either group. In group (1) no patient had a hydrocele
      after surgery. By contrast, in group (2) there were four cases of secondary
      hydrocele (10%; P = 0.041)); no testicular hypertrophy was observed following
      lymphatic sparing surgery; One patient in each group had varicocele recurrence.
      Pregnancy was reported in 30 patients (37.5%) during the follow-up period, 17 of
      them (42.5%) were group (1) difference was not significantly different among both
      groups. CONCLUSIONS: Subinguinal varicocelectomy using combination of optical
      magnification and lymphatic staining (methylene blue) offers simple and quick
      preservation of the draining lymphatic vessels and avoids secondary hydrocele
      formation. ClinicalTrials.gov ID: NCT01259258.

PMID- 21875698
TI  - Comparative proteome analysis of Brucella abortus 2308 and its virB type IV
      secretion system mutant reveals new T4SS-related candidate proteins.
AB  - Brucella abortus is an alpha-2 proteobacteria with a type IV secretion system
      (T4SS) known as virB, which is necessary to gain virulence by building up a
      replicative vacuole associated with the endoplasmic reticulum of the host cell. A
      virB T4SS mutant of the B. abortus 2308 strain and its wild-type strain were
      grown in acid medium in order to obtain and analyze their proteomes, looking for
      putative proteins that may serve as T4SS substrates and those that may be
      subjected to T4SS regulation. A total of 47 overexpressed and 22 underexpressed
      proteins from the virB T4SS mutant strain were selected and sequenced. Some of
      the 69 analyzed proteins have not been described before either as over or under
      expressed in relation to a virB T4SS mutation, whereas some of them have been
      already described by other groups as potentially important secretory proteins in
      other Brucella species. An important number of the proteins identified are outer
      membrane and periplasmic space protein, which makes them become particularly
      important new T4SS-related candidate proteins.

PMID- 21875700
TI  - The emergence of connectivity in neuronal networks: from bootstrap percolation to
      auto-associative memory.
AB  - We consider a random synaptic pruning in an initially highly interconnected
      network. It is proved that a random network can maintain a self-sustained
      activity level for some parameters. For such a set of parameters a pruning is
      constructed so that in the resulting network each neuron/node has almost equal
      numbers of in- and out-connections. It is also shown that the set of parameters
      which admits a self-sustained activity level is rather small within the whole
      space of possible parameters. It is pointed out here that the threshold of
      connectivity for an auto-associative memory in a Hopfield model on a random graph
      coincides with the threshold for the bootstrap percolation on the same random
      graph. It is argued that this coincidence reflects the relations between the auto
      associative memory mechanism and the properties of the underlying random network
      structure. This article is part of a Special Issue entitled "Neural Coding".

PMID- 21875699
TI  - A biomechanical assessment of floor and overhead lifts using one or two
      caregivers for patient transfers.
AB  - This study investigated the differences in peak external hand forces and external
      moments generated at the L5/S1 joint of the low back due to maneuvering loaded
      floor-based and overhead-mounted patient lifting devices using one and two
      caregivers. Hand forces and external moments at the L5/S1 joint were estimated
      from ground reaction forces and motion capture data. Caregivers gave ratings of
      perceived exertion as well as their opinions regarding overhead vs. floor lifts.
      Use of overhead lifts resulted in significantly lower back loads than floor
      lifts. Two caregivers working together with a floor lift did not reduce loads on
      the primary caregiver compared to the single-caregiver case. In contrast, two
      caregiver operation of an overhead lift did result in reduced loads compared to
      the single-caregiver case. Therefore, overhead lifts should be used whenever
      possible to reduce the risk of back injury to caregivers. The use of two
      caregivers does not compensate for the poorer performance of floor lifts.

PMID- 21875701
TI  - Do not neglect small troubles: moderately negative stimuli affect target
      processing more intensely than highly negative stimuli.
AB  - Though the humans are more susceptible to unpleasant stimuli of higher intensity,
      how the valence intensity of unpleasant stimuli impacts subsequent cognitive
      processing, and whether this impact increases with the unpleasantness, require
      clarification. For this purpose, event-related potentials (ERPs) were recorded
      for highly negative (HN), mildly negative (MN) and neutral cueing pictures, and
      subsequently for the non-emotional target picture while subjects were required to
      discriminate the location of the target. Cue-induced ERPs showed more negative
      deflections for the HN than for the neutral pictures in the 450-650 ms time
      interval. The emotion effect for the MN cueing stimuli, however, was non
      significant in this interval. In contrast, target-induced P3 amplitudes were
      significantly more negative following MN versus neutral cueing pictures, while
      the P3 amplitudes were not significantly different between HN and neutral
      conditions, irrespective of cueing validity. Thus, despite weak immediate impact,
      MN stimuli influenced subsequent target processing more heavily than HN stimuli.
      This suggests that the impact of unpleasant events on cognition doesn't
      necessarily increase with the unpleasantness. Mild unpleasant stimulus, which is
      weak in immediate emotion arousal, should not be neglected due to the likelihood
      of producing a sustained impact.

PMID- 21875702
TI  - Cortical attractor network dynamics with diluted connectivity.
AB  - The connectivity of the cerebral cortex is diluted, with the probability of
      excitatory connections between even nearby pyramidal cells rarely more than 0.1,
      and in the hippocampus 0.04. To investigate the extent to which this diluted
      connectivity affects the dynamics of attractor networks in the cerebral cortex,
      we simulated an integrate-and-fire attractor network taking decisions between
      competing inputs with diluted connectivity of 0.25 or 0.1, and with the same
      number of synaptic connections per neuron for the recurrent collateral synapses
      within an attractor population as for full connectivity. The results indicated
      that there was less spiking-related noise with the diluted connectivity in that
      the stability of the network when in the spontaneous state of firing increased,
      and the accuracy of the correct decisions increased. The decision times were a
      little slower with diluted than with complete connectivity. Given that the
      capacity of the network is set by the number of recurrent collateral synaptic
      connections per neuron, on which there is a biological limit, the findings
      indicate that the stability of cortical networks, and the accuracy of their
      correct decisions or memory recall operations, can be increased by utilizing
      diluted connectivity and correspondingly increasing the number of neurons in the
      network, with little impact on the speed of processing of the cortex. Thus
      diluted connectivity can decrease cortical spiking-related noise. In addition, we
      show that the Fano factor for the trial-to-trial variability of the neuronal
      firing decreases from the spontaneous firing state value when the attractor
      network makes a decision. This article is part of a Special Issue entitled
      "Neural Coding".

PMID- 21875703
TI  - Involvement of nitric oxide in granisetron improving effect on scopolamine
      induced memory impairment in mice.
AB  - Granisetron, a serotonin 5-HT(3) receptor antagonist, widely used as an
      antiemetic drug following chemotherapy, has been found to improve learning and
      memory. In this study, effects of granisetron on spatial recognition memory and
      fear memory and the involvement of nitric oxide (NO) have been determined in a Y
      maze and passive avoidance test. Granisetron (3, 10mg/kg, intraperitoneally) was
      administered to scopolamine-induced memory-impaired mice prior to acquisition,
      consolidation and retrieval phases, either in the presence or in the absence of a
      non-specific NO synthase inhibitor, l-NAME (3, 10mg/kg, intraperitoneally); a
      specific inducible NO synthase (iNOS) inhibitor, aminoguanidine (100mg/kg); and a
      NO precursor, l-arginine (750 mg/kg). It is demonstrated that granisetron
      improved memory acquisition in a dose-dependent manner, but it was ineffective on
      consolidation and retrieval phases of memory. The beneficial effect of
      granisetron (10mg/kg) on memory acquisition was significantly reversed by l-NAME
      (10mg/kg) and aminoguanidine (100mg/kg); however, l-arginine (750 mg/kg) did not
      potentiate the effect of sub-effective dose of granisetron (3mg/kg) in memory
      acquisition phase. It is concluded that nitric oxide is probably involved in
      improvement of memory acquisition by granisetron in both spatial recognition
      memory and fear memory. This article is part of a Special Issue entitled The
      Cognitive Neuroscience.

PMID- 21875704
TI  - Development of peritoneal macrophage along a dendritic cell lineage in response
      to uptake of oligomannose-coated liposomes.
AB  - In this study, we investigate the potential of peritoneal macrophages to
      differentiate into dendritic cell (DCs) in response to preferential uptake of
      oligomannose-coated liposomes (OMLs). About 30% of peritoneal cells (PECs)
      preferentially took up OMLs that were administered into the peritoneal cavity.
      The OML-ingesting cells expressed CD11b and F4/80, but lacked CD11c expression,
      indicating that the OML-ingesting PECs with a CD11b(high)CD11c(-) phenotype are
      resident peritoneal macrophages. During in vitro cultivation, CD11c(+) cells
      arose among the PECs with ingested OMLs. CD11c(+) cells also developed among
      enriched peritoneal CD11b(high)CD11(-) cells from OML-treated mice, and the
      resulting CD11c(+) cells expressed co-stimulatory molecules and MHC class II. In
      addition, OML-ingesting CD11b(high)CD11c(+) cells were found in spleen after the
      enriched peritoneal macrophages with ingested OMLs were transplanted in the
      peritoneal cavity of mice. These results show that a fraction of peritoneal
      macrophages can differentiate into mature DCs following uptake of OMLs.

PMID- 21875706
TI  - Deformation and degradation of polymers in ultra-high-pressure liquid
      chromatography.
AB  - Ultra-high-pressure liquid chromatography (UHPLC) using columns packed with sub-2
      MUm particles has great potential for separations of many types of complex
      samples, including polymers. However, the application of UHPLC for the analysis
      of polymers meets some fundamental obstacles. Small particles and narrow bore
      tubing in combination with high pressures generate significant shear and
      extensional forces in UHPLC systems, which may affect polymer chains. At high
      stress conditions flexible macromolecules may become extended and eventually the
      chemical bonds in the molecules can break. Deformation and degradation of
      macromolecules will affect the peak retention and the peak shape in the
      chromatogram, which may cause errors in the obtained results (e.g. the calculated
      molecular-weight distributions). In the present work we explored the limitations
      of UHPLC for the analysis of polymers. Degradation and deformation of
      macromolecules were studied by collecting and re-injecting polymer peaks and by
      off-line two-dimensional liquid chromatography. Polystyrene standards with
      molecular weight of 4 MDa and larger were found to degrade at UHPLC conditions.
      However, for most polymers degradation could be avoided by using low linear
      velocities. No degradation of 3-MDa PS (and smaller) was observed at linear
      velocities up to 7 mm/s. The column frits were implicated as the main sources of
      polymer degradation. The extent of degradation was found to depend on the type of
      the column and on the column history. At high flow rates degradation was observed
      without a column being installed. We demonstrated that polymer deformation
      preceded degradation. Stretched polymers eluted from the column in slalom
      chromatography mode (elution order opposite to that in SEC or HDC). Under certain
      conditions we observed co-elution of large and small PS molecules though a
      convolution of slalom chromatography and hydrodynamic chromatography.

PMID- 21875705
TI  - Technique and outcomes of isolated limb infusion for locally advanced malignant
      melanoma--a radiological perspective.
AB  - AIM: Isolated limb infusion (ILI) is a novel, minimally invasive technique for
      delivering high-dose regional chemotherapy in patients with recurrent and in
      transit melanoma. The aim of this study was to review our single-centre
      experience in treating eleven patients. We emphasize the role of radiologists in
      setting up this service, including pre-treatment workup and placement of vascular
      catheters. MATERIALS AND METHODS: A retrospective analysis of 11 patients who
      underwent 12 procedures between 2005 and 2009 was performed. Pre-procedural
      staging computed tomography (CT), CT angiography, and duplex studies were
      performed. All patients received a cytotoxic combination of melphalan and
      actinomycin-D via radiologically placed arterial and venous catheters in the
      affected limb under mild hyperthermic conditions. The outcome measures include
      response rates, limb toxicity, complications, and survival. RESULTS: All patients
      were female with a mean age of 72 years. Three patients had American Joint
      Committee on Cancer (AJCC) stage IIIB melanoma, seven had stage IIIC melanoma,
      and one had a stage IIIB Merkel cell tumour. Complete response was seen in five
      patients (46%), partial response in four (36%), and progressive disease in two
      (18%). One patient developed grade 4 toxicity requiring a fasciotomy and another
      experienced systemic toxicity. CONCLUSION: These outcomes are comparable to
      previous studies and shows that ILI is effective in locoregional control of
      unresectable melanoma. It is a relatively safe procedure but not without risk.
      Our experience shows the importance of radiological input to ensure safe and
      effective delivery of services.

PMID- 21875707
TI  - Determination of chloropropanols in foods by one-step extraction and
      derivatization using pressurized liquid extraction and gas chromatography-mass
      spectrometry.
AB  - 3-Chloropropane-1,2-diol (3-MCPD) and 1,3-dichloro-2-propanol (1,3-DCP) were
      determined for the first time in bakery foods using pressurized liquid extraction
      (PLE) combined with in situ derivatization and GC-MS analysis. This one-step
      protocol uses N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) as silylation
      reagent. Initially, screening experimental design was applied to evaluate the
      effects of the variables potentially affecting the extraction process, namely
      extraction time (min) and temperature ( degrees C), number of cycles, dispersant
      reagent (diatomaceous earth in powder form and as particulate matter with high
      pore volume Extrelut NT) and percent of flush ethyl acetate volume (%). To reduce
      the time of analysis and improve the sensitivity, derivatization of the compounds
      was performed in the cell extraction. Conditions, such as the volume of BSTFA,
      temperature and time for the in situ derivatization of analytes using PLE, were
      optimized by a screening design followed to a Doehlert response surface design.
      The effect of the in-cell dispersants/adsorbents with diatomaceous earth,
      Florisil and sodium sulfate anhydrous was investigated using a Box-Behnken
      design. Using the final best conditions, 1 g of sample dispersed with 0.1 g of
      sodium sulfate anhydrous and 2.5 g diatomaceous earth was extracted with ethyl
      acetate. 1 g of Florisil, as clean-up adsorbent, and 70 MUL of BSTFA were used
      for 3 min at 70 degrees C. Under the optimum conditions, the calibration curves
      showed good linearity (R(2)>0.9994) and precision (relative standard deviation,
      RSD<=2.4%) within the tested ranges. The limits of quantification for 1,3-DCP and
      3-MCDP, 1.6 and 1.7 MUg kg(-1), respectively, are far below the established
      limits in the European and American legislations. The accuracy, precision,
      linearity, and limits of quantification provided make this analytical method
      suitable for routine control. The method was applied to the analysis of several
      toasted bread, snacks, cookies and cereal samples, none of which contained
      chloropropanols at concentrations above the legislation levels.

PMID- 21875708
TI  - Hierarchically structured meso-macroporous aluminosilicates with high tetrahedral
      aluminium content in acid catalysed esterification of fatty acids.
AB  - A simple synthesis pathway has been developed for the design of hierarchically
      structured spongy or spherical voids assembled meso-macroporous aluminosilicates
      with high tetrahedral aluminium content on the basis of the aqueous
      polymerisation of new stabilized alkoxy-bridged single molecular precursors. The
      intimate mixing of an aluminosilicate ester (sec-BuO)(2)-Al-O-Si(OEt)(3) and a
      silica co-reactant (tetramethoxysilane, TMOS) with variable ratios and the use of
      alkaline solutions (pH 13.0 and 13.5) improve significantly the
      heterocondensation rates between the highly reactive aluminium alkoxide part of
      the single precursor and added silica co-reactant, leading to aluminosilicate
      materials with high intra-framework aluminium content and low Si/Al ratios. The
      spherically-shaped meso-macroporosity was spontaneously generated by the release
      of high amount of liquid by-products (water/alcohol molecules) produced during
      the rapid hydrolysis and condensation processes of this double alkoxide and the
      TMOS co-reactant. It has been observed that both pH value and Al-Si/TMOS molar
      ratio can strongly affect the macroporous structure formation. Increasing pH
      value, even slightly from 13 to 13.5, can significantly favour the incorporation
      of Al atoms in tetrahedral position of the framework. After the total ionic
      exchange of Na(+) compensating cations, catalytic tests of obtained materials
      were realised in the esterification reaction of high free fatty acid (FFA) oils,
      showing their higher catalytic activity compared to commercial Bentonite clay,
      and their potential applications as catalyst supports in acid catalysed
      reactions.

PMID- 21875709
TI  - Immbolization of uricase enzyme in Langmuir and Langmuir-Blodgett films of fatty
      acids: possible use as a uric acid sensor.
AB  - Preserving the enzyme structure in solid films is key for producing various
      bioelectronic devices, including biosensors, which has normally been performed
      with nanostructured films that allow for control of molecular architectures. In
      this paper, we investigate the adsorption of uricase onto Langmuir monolayers of
      stearic acid (SA), and their transfer to solid supports as Langmuir-Blodgett (LB)
      films. Structuring of the enzyme in beta-sheets was preserved in the form of 1
      layer LB film, which was corroborated with a higher catalytic activity than for
      other uricase-containing LB film architectures where the beta-sheets structuring
      was not preserved. The optimized architecture was also used to detect uric acid
      within a range covering typical concentrations in the human blood. The approach
      presented here not only allows for an optimized catalytic activity toward uric
      acid but also permits one to explain why some film architectures exhibit a
      superior performance.

PMID- 21875710
TI  - Wetting films on chemically patterned surfaces.
AB  - The behavior of thin wetting films on chemically patterned surfaces was
      investigated. The patterning was performed by means of imprinting of micro-grid
      on methylated glass surface with UV-light (lambda=184.8 nm). Thus imprinted image
      of the grid contained hydrophilic cells and hydrophobic bars on the glass
      surface. For this aim three different patterns of grids were utilized with small,
      medium and large size of cells. The experiment showed that the drainage of the
      wetting aqueous films was not affected by the type of surface patterning.
      However, after film rupturing in the cases of small and medium cells of the
      patterned grid the liquid from the wetting film underwent fast self-organization
      in form of regularly ordered droplets covering completely the cells of the grid.
      The droplets reduced significantly their size upon time due to evaporation. In
      the cases of the largest cell grid, a wet spot on the place of the imprinted grid
      was formed after film rupturing. This wet spot disassembled slowly in time. In
      addition, formation of a periodical zigzag three-phase contact line (TPCL) was
      observed. This is a first study from the planned series of studies on this topic.

PMID- 21875711
TI  - Effect of nanoparticle aggregation at low concentrations of TiO2 on the
      hydrophilicity, morphology, and fouling resistance of PES-TiO2 membranes.
AB  - This paper reports the fabrication and characterization of polyethersulfone
      TiO(2) (PES-TiO(2)) nanoparticle composite membranes made from synthesis casting
      solution consisting of various compositions of polymer solvents (DMF and EtOH)
      and TiO(2) additive. The results also revealed that the membrane permeation and
      rejection rates, pore size, and porosity were dependent on the TiO(2) and EtOH
      concentrations. Nanoparticles were characterized by zeta potential measurements,
      TEM observations, and measurement of particle size distributions. Zeta potential
      measurements in aqueous solution demonstrated that the TiO(2) particles size is
      dominated by electric double layer interactions. Addition of EtOH promotes the
      increase of the clusters size as consequence of a double effect: reduction of the
      dielectric constant of solution and the depletion of the suspension field
      determined by the action of the polymer chains. The observed effects as result of
      EtOH addition and increase of TiO(2) concentration were similar: both procedures
      provoked an increase of macrovoid dimensions. The modified membranes by TiO(2)
      incorporation showed a structural change from a sponge-like to a finger-like
      structure. Strong correlations were observed between the hydrophilicity and the
      permeability of manufactured membranes. The formation mechanism of TiO(2)-blended
      membranes was altered, in a similar way, as result of EtOH at different contents
      of nanoparticles. Fouling resistance of modified membranes was significantly
      improved showing that EtOH addition is a suitable procedure for the membrane
      performance improvement. The rejection potential of membranes is hardly affected
      by the nanoparticles and EtOH incorporation into the polymeric solution.

PMID- 21875712
TI  - Aggregation of nanoparticles in a block copolymer bilayer.
AB  - In this paper, we examine, by dissipative particle dynamics (DPD) simulation, the
      interactions between nanoparticles and block copolymer bilayer membranes. The
      bilayer has a hydrophobic core and hydrophilic head groups on both sides of the
      core. Nanoparticles without or with a grafted homopolymer are considered. For the
      conditions investigated, the single nanoparticles and small aggregates are
      located at the interfaces of the membrane, namely the interfaces between the
      hydrophilic domains of the membrane and the solvent as well as at the interface
      between the hydrophobic and hydrophilic domains of the membrane. The large
      aggregates are located in the hydrophilic domains. By increasing the length of
      the homopolymer grafted on the nanoparticles, the size of the aggregates in the
      membrane decreases. At relatively short DPD step times, the particles aggregate
      in the solvent. As the time increases, the single particles and aggregates
      penetrate into the membrane.

PMID- 21875713
TI  - Microwave synthesis of BiPO4 nanostructures and their morphology-dependent
      photocatalytic performances.
AB  - A facile and rapid microwave irradiation method was explored for the synthesis of
      bismuth phosphate (BiPO(4)) nanostructures with various morphologies and phases
      in different solvents. The BiPO(4) products were characterized by powder X-ray
      diffraction (XRD), Raman spectroscopy, scanning electron microscopy (SEM),
      transmission electron microscopy (TEM), high resolution transmission electron
      microscopy (HRTEM), UV-vis diffuse reflection spectroscopy (DRS). The effect of
      the solvents on the formation of the BiPO(4) nanostructures was discussed on the
      basis of experimental results. The different BiPO(4) nanostructures exhibited
      different optical properties, BET surface areas and photocatalytic activities on
      the degradation of methyl orange (MO) under UV and visible light irradiation. The
      experimental results suggested that the photocatalytic activity was closely
      relative with the crystalline phase and band gap of BiPO(4). Hexagonal BiPO(4)
      nanoparticles with narrow band gap showed the highest photocatalytic performance.

PMID- 21875714
TI  - Gelation of ionic liquid with exfoliated montmorillonite nanoplatelets and its
      application for quasi-solid-state dye-sensitized solar cells.
AB  - The exfoliated montmorillonite (exMMT) nanoplatelets that carry negative charges
      are capable of adsorbing 1-methyl-3-propyl-imidazolium cations to form a gel-type
      ionic liquid-based electrolyte system for dye-sensitized solar cell (DSSC).
      Interestingly, it also increases the power conversion efficiency of DSSC from
      6.58% to 7.77% at full sun. The increased efficiency is attributed to the
      decreased resistance of gel electrolyte system and enhanced reduction reaction
      rate at the counter electrode, both of which are related to the two-dimensional
      electrolyte nature of exMMTs that repel the I(-)/I(3)(-) redox couples toward
      their major conduction pathway.

PMID- 21875715
TI  - Do infants recognize the Arcimboldo images as faces? Behavioral and near-infrared
      spectroscopic study.
AB  - Arcimboldo images induce the perception of faces when shown upright despite the
      fact that only nonfacial objects such as vegetables and fruits are painted. In
      the current study, we examined whether infants recognize a face in the Arcimboldo
      images by using the preferential looking technique and near-infrared spectroscopy
      (NIRS). In the first experiment, we measured looking preference between upright
      and inverted Arcimboldo images among 5- and 6-month-olds and 7- and 8-month-olds.
      We hypothesized that if infants perceive the Arcimboldo images as faces, they
      would prefer the upright images to the inverted ones. We found that only 7- and 8
      month-olds significantly preferred upright images, suggesting that they could
      perceive the Arcimboldo images as faces. In the second experiment, we measured
      hemodynamic responses using NIRS. Based on the behavioral data, we hypothesized
      that 7- and 8-month-olds would show different neural activity for upright and
      inverted Arcimboldo images, as do adults. Therefore, we measured hemodynamic
      responses in 7- and 8-month-olds while they were looking at upright and inverted
      Arcimboldo images. Their responses were then compared with the baseline
      activation during the presentation of individual vegetables. We found that the
      concentration of oxyhemoglobin increased in the left temporal area during the
      presentation of the upright images compared with the baseline during the
      presentation of vegetables. The results of the two experiments suggest that (a)
      the ability to recognize the upright Arcimboldo images as faces develops at
      around 7 or 8 months of age and (b) processing of the upright Arcimboldo images
      is related to the left temporal area of the brain.

PMID- 21875716
TI  - Misidentification of a transverse occipital suture as a persistent mendosal
      suture.

PMID- 21875717
TI  - Unbound bilirubin does not increase during ibuprofen treatment of patent ductus
      arteriosus in preterm infants.
AB  - OBJECTIVE: To determine whether ibuprofen displaces bilirubin from albumin in
      preterm infants. STUDY DESIGN: A total of 34 preterm neonates (<32 weeks
      gestation) treated by ibuprofen (10-5-5 mg/kg) were included in this prospective
      open-label study. Total bilirubin (TB), unbound bilirubin (UB), and ibuprofen
      concentrations were measured before, 1 hour, and 6 hours after the first dose;
      before and 1 hour after the second dose; and 72 hours after the beginning of
      treatment. The infants were screened by auditory brainstem responses and by
      neurologic examination at term. RESULTS: At baseline, TB, UB, apparent binding
      affinity of albumin (Ka), and albumin concentrations were 6.0+/-1.6 mg/dL, 1.9+/
      2.2 MUg/dL, 14.1+/-5.8 L.MUmol(-1), and 28.7+/-2.3 g/L, respectively. Ibuprofen
      treatment had no effect on TB, UB, or Ka values. No correlation between UB or Ka
      and ibuprofen concentrations was found. No neurologic symptoms or significant
      modifications of auditory brainstem responses were observed at term. CONCLUSION:
      Ibuprofen (10-5-5 mg/kg) did not displace bilirubin in preterm infants with a
      baseline TB concentration <8.8 mg/dL.

PMID- 21875718
TI  - Carotid intima-media thickness at 7 years of age: relationship to C-reactive
      protein rather than adiposity.
AB  - OBJECTIVE: According to the concept of adipose tissue expandability, the vascular
      complications of obesity are related less to the amount of stored fat than to the
      low-grade inflammation that excess fat storage may elicit. We tested this concept
      in 7-year-old children by assessing whether carotid intima-media thickness (cIMT)
      is related to obesity measures or to circulating highly sensitive C-reactive
      protein (hsCRP), as a marker of low-grade inflammation. STUDY DESIGN: The study
      group comprised 135 asymptomatic Caucasian children (72 girls and 63 boys; mean
      age, 7.1+/-1.1 years) with normal height and weight distributions. Relationships
      were assessed among cIMT, hsCRP, obesity measures (ie, body mass index [BMI],
      total fat by bioelectric impedance, and visceral fat by ultrasound), insulin
      resistance (by the homeostasis model assessment for insulin resistance), and
      fasting serum lipid levels. RESULTS: cIMT was correlated with hsCRP, but not with
      BMI or body fat; the regression coefficients between cIMT and hsCRP (adjusted for
      age, sex, BMI, body fat, and serum lipid levels) were fairly similar across all
      BMI categories (beta=0.370-0.411; all P<.001 to<.0001). Serum hsCRP increased
      with increasing BMI, total fat, and visceral fat (all P<.001). CONCLUSION: At age
      7 years, cIMT is already associated with low-grade inflammation, as measured by
      hsCRP, but not with BMI or body fat. These findings imply that public health
      strategies aimed at early prevention of cardiovascular disease may need to target
      low-grade inflammation rather than only BMI or adiposity.

PMID- 21875720
TI  - Predictors of persistence of social anxiety disorder: a national study.
AB  - Social anxiety disorder (SAD) is highly prevalent and impairing. Little is known
      about rates and predictors of persistence of SAD in the community. The current
      study derived data from the National Epidemiologic Survey on Alcohol and Related
      Conditions, Wave 1 (2001-2002, n = 43,093) and Wave 2 (2004-2005, n = 34,653), a
      large survey of a representative sample of the United States adult population.
      Individuals with current DSM-IV SAD at Wave 1 were re-interviewed 3 years later
      at Wave 2 using the Alcohol Use Disorder and Associated Disabilities Interview
      Schedule-DSM IV Version (AUDADIS-IV). We found that in the community, 22.3% of
      respondents with SAD at the Wave 1 evaluation met DSM-IV criteria for SAD three
      years later, and endorsement of social interaction fears and a higher number of
      avoided social situations, treatment-seeking during past year, and comorbidity
      with mood disorders independently predicted persistence of SAD. These results
      suggest that persistence of SAD in the community is common and associated with
      symptom severity and comorbid mood disorders.

PMID- 21875722
TI  - Nationwide survey of neuro-specialists' opinions on anticoagulant therapy after
      intracerebral hemorrhage in patients with atrial fibrillation.
AB  - PURPOSE: A nationwide survey was conducted regarding anticoagulant therapy in
      patients with acute intracerebral hemorrhage (ICH) on warfarin with nonvalvular
      atrial fibrillation (NVAF). METHODS: A questionnaire on standard therapeutic
      strategy for warfarin-related ICH in patients with NVAF was mailed to 416
      institutes. RESULTS: A total of 329 physicians (79%) responded with a completed
      questionnaire. On admission, all respondents stopped warfarin medication and 94%
      normalized the international normalized ratio (INR) mainly by Vitamin K (63%),
      followed by fresh frozen plasma (20%), and prothrombin complex concentrate (10%).
      Afterwards, 91% of the respondents restarted anticoagulation and 3% used
      antiplatelet for prevention of thromboembolism, but the remaining 6% disagreed
      with restarting antithrombotic therapy. As contraindications for resuming
      anticoagulation, recurrent ICH (59%) and poor functional condition (59%) were
      often chosen. Of those who restarted anticoagulation, the timing was within 4
      days in 7%, 5 to 7 days in 21%, 8 to 14 days in 25%, 15 to 28 days in 28% and 29
      days or later in 18%. The major key finding on follow-up CT to restart
      anticoagulation was the absorption tendency of hematomas (47%). When restarting
      anticoagulation, 76% of the respondents used warfarin alone and 20% used either
      unfractionated heparin plus warfarin or heparin alone. CONCLUSION: A large
      majority of respondents responsible for ICH management stopped oral warfarin
      medication and normalized INR on admission, and restarted anticoagulation after
      acute ICH in patients with NVAF. However, the strategies to normalize INR and to
      restart anticoagulant therapy varied greatly and depended on each individual
      physician's decision.

PMID- 21875721
TI  - Neuropathology and behavioral impairments after three types of global ischemia
      surgery in Meriones unguiculatus: evidence in motor cortex, hippocampal CA1
      region and the neostriatum.
AB  - The effects of three types of global ischemia by occlusion of carotid artery on
      motor and exploratory behaviors of Gerbils were evaluated by the Activity Cage
      and Rota rod tests. Animals were divided based on two surgical criteria:
      unilateral (UNI) or bilateral (BIL) carotid occlusion, with (REP) or without
      (OCL) reperfusion; and their behavior was evaluated on the fourth (4) or sixth
      (6) day. There was reduction of cell number in striatum, motor cortex M1 area,
      and hippocampal CA1 area in all groups in comparison to control animals. For M1
      area and striatum, the largest reduction was observed in UNI6, UNI4, and BIL4
      groups. Neuronal loss was also observed in CA1 area of BIL4 rodents. There was a
      decrease in crossings and rearings in all groups in activity cage test, compared
      to control. Reperfusion, unilateral and bilateral occlusion groups showed
      decrease in crossings. Only the BIL4 showed a decrease of rearing. In the Rota
      rod test, except the UNIOCL6, the groups showed a decrease in the balance in
      comparison to control. Both groups with REP4 showed a major decrease in balance.
      These findings suggest that both unilateral and bilateral carotid occlusions with
      reperfusion produce impairments of motor and exploratory behavior.

PMID- 21875719
TI  - Hypothermia and other treatment options for neonatal encephalopathy: an executive
      summary of the Eunice Kennedy Shriver NICHD workshop.

PMID- 21875723
TI  - CCG polymorphisms in the huntingtin gene have no effect on the pathogenesis of
      patients with Huntington's disease in mainland Chinese families.
AB  - Huntington's disease (HD) is caused by the abnormal expansion of CAG repeats in
      the huntingtin gene (HTT). The adjacent proline-rich region, which also has a CCG
      polymorphism among people of different races, may also affect the pathogenesis of
      HD. To study the effect of this polymorphism on patients with HD in mainland
      China, 53 HD mutant alleles were examined. The results showed that 54.72% of the
      HD mutant alleles had 10-repeat alleles, and the remaining 45.28% had 7-repeat
      alleles. Moreover, comparison of the clinical features between the two groups
      revealed no significant difference. We also investigated its effect on the
      aggregates in vitro. No significant difference was detected when the morphology
      and size of the aggregates with the two polymorphisms was compared in cells.
      Given these findings, it was quite reasonable to suppose that the CCG
      polymorphism may not influence the pathogenesis of patients with HD in mainland
      China.

PMID- 21875724
TI  - Short-term risk and predictors of stroke after transient ischemic attack.
AB  - BACKGROUND: Transient ischemic attack (TIA) is a marker of stroke, especially in
      the early phase following this event. The aims of this study are to determine the
      short-term risk of stroke and to evaluate the independent predictors of stroke in
      patients with TIA who are hospitalized within 48 hours after symptom onset.
      METHODS: During a 36-month period (beginning in November 2007), 3554 patients
      (mean age: 70.5 +/- 13 years; 49.9% female; mean NIHSS score: 1.4 +/- 2.5) from
      15 hospitals suffering from TIA were prospectively evaluated. RESULTS: Of the
      3554 patients, 43 (1.2%) suffered from stroke during hospitalization (6.5 +/- 4.3
      days). We identified the following independent predictors for stroke after TIA:
      male sex (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.3-5; P=0.008),
      age >=65 years (OR, 4.7; 95% CI, 1.4-15; P=0.01), hyperlipidemia (OR, 2.4; 95%
      CI, 1.2-4.8; P=0.015), and dysarthria (OR, 2; 95% CI, 1.1-5.0; P=0.038).
      CONCLUSION: Patient characteristics (male sex, age, and hyperlipidemia) and TIA
      symptom (dysarthria) may be useful in defining stroke after TIA in patients who
      were hospitalized with TIA.

PMID- 21875725
TI  - Disturbance of real space navigation in moderately advanced but not in early
      Huntington's disease.
AB  - BACKGROUND: Visuospatial skills including spatial navigation are known to be
      impaired in Huntington's disease. Spatial navigation comprises two navigational
      frameworks, allocentric and egocentric. Several studies have associated the
      allocentric navigation with the hippocampus and the egocentric navigation with
      the striatum. The striatum is predominantly impaired from the early stages of
      Huntington's disease. OBJECTIVE: To find whether spatial navigation impairment is
      present in the early stages of Huntington's disease and to test the hypothesis
      that the egocentric navigation is predominantly affected compared to the
      allocentric navigation. METHODS: In nineteen patients with Huntington's disease
      the egocentric and the allocentric navigation skills were tested using the Blue
      Velvet Arena, a human analog of Morris Water Maze, and compared to nineteen age
      and gender-matched healthy controls. Cognitive functions, with emphasis on the
      executive functions, were also assessed. RESULTS: The spatial navigation skills
      deteriorated with the increasing motor impairment in Huntington's disease. These
      changes only became apparent in patients with moderate functional impairment. No
      difference between the egocentric and the allocentric skills was seen.
      DISCUSSION: Spatial navigation deficit is not an early marker of the cognitive
      dysfunction in Huntington's disease. We speculate that the striatal circuitry
      that is known to degenerate early in the course of Huntington's disease is not
      directly associated with the spatial navigation.

PMID- 21875726
TI  - Assessment of noise levels generated by music shops in an urban city in Nigeria.
AB  - OBJECTIVE: To assess the level of noise generated by music shops in an urban city
      in Nigeria. STUDY DESIGN: Cross-sectional, descriptive study. METHODOLOGY: The
      study involved music shops in three out of eight identified clusters of market
      areas in Benin City. A semi-structured, researcher-administered questionnaire was
      also used to collect data from music shop owners. Noise levels generated by
      speakers in the music shops were measured using a sound level meter, and blood
      pressure measurements were taken with a mercury sphygmomanometer. RESULTS: Of the
      250 music shops studied, more than 90.0% generated noise levels >85 dB, and 54.8%
      had a continuous pattern of noise. Longer duration of working years was
      significantly associated with decreased hearing (P = 0.01), shouting when talking
      (P = 0.04) and high blood pressure (P = 0.003). The position of music dealers in
      relation to the speakers was significantly associated with shouting when talking
      (P = 0.000). A significant association was found between higher levels of noise
      and high blood pressure (P = 0.004). CONCLUSION: This study found very high
      levels of noise in music shops, which could be a source of occupational noise
      exposure among music dealers. Enlightenment campaigns on the hazards of exposure
      to loud noise and periodic audiometry examinations are recommended for this
      occupational group.

PMID- 21875727
TI  - Preliminary report on the expression of leptin and leptin receptor (ObR) in
      normal, hyperplastic and neoplastic canine mammary tissues.
AB  - Leptin and its receptor (ObR) expression were investigated by
      immunohistochemistry in normal, hyperplastic and neoplastic canine mammary
      tissues and related to clinical-pathological features. Leptin expression was
      detected in healthy mammary tissues, adenosis and in benign mammary tumours and
      was lower in ductal hyperplasias and malignant tumours. A high percentage of ObR
      positive cells were present in adenosis, benign tumours and in complex
      carcinomas, while ObR expression was lower in healthy mammary tissues, in ductal
      hyperplasias and in a large part of invasive mammary carcinomas. Our data
      demonstrated that cancer cells expressed at low level leptin and ObR in canine
      mammary tumours with a more aggressive behaviour, as well as in lymph node
      metastases. Consequently, leptin and ObR expressions in this species resulted to
      be not associated with a reduced overall survival.

PMID- 21875728
TI  - Histological and immunohistochemical studies of changes in myenteric plexuses and
      in interstitial cells of Cajal associated with equine colic.
AB  - In this study we investigated the histological changes of the myenteric plexuses
      and interstitial cells of Cajal (ICC) in gut samples from horses with colic to
      try to find results useful in the prognostic evaluation of enteric lesions. A
      morphologic and quantitative study of myenteric ganglia, ganglion cells and
      neuronal chromatolytic and necrotic changes of 24 horses with colic was
      performed. For ganglion cells, enteroglial cells and ICC immunolabeling was also
      performed to identify cell functional disorders. A significant increase of
      neuronal chromatolysis and necrosis occurred in horses suffering from colic
      throughout the gut. The neuron-specific enolase (NSE) and synaptophysin
      immunoreaction quantified with image analysis showed a significant loss of
      neuronal activity in all intestinal tracts of the animals under study associated
      with a significant loss of ICC immunoreactivity. The results supports
      immunohistochemical evaluation of ENS and ICC as a useful tool along with
      morphometric investigations in the evaluation of gut lesions produced during
      colic syndrome.

PMID- 21875729
TI  - Accidental fatal aflatoxicosis due to contaminated commercial diet in 50 dogs.
AB  - Aflatoxins, produced by Aspergillus spp., are toxic contaminants of stored grain.
      This study describes 50 dogs presented with foodborne aflatoxicosis. Common
      clinical signs included lethargy (78%), vomiting (76%), anorexia (74%), icterus
      (66%), depression (66%), melena (60%), haematuria (36%) and diarrhoea (36%).
      Common laboratory abnormalities included increased activities of aspartate
      aminotransferase (86%), alkaline phosphatase (84%) and alanine aminotransferase
      (79%), hypoantithrombinaemia (86%), prolonged prothrombin (PT, 82%) and activated
      partial thromboplastin times (aPTT, 80%), hyperbilirubinaemia (73%),
      hypocholesterolaemia (60%) hypoalbuminemia (47%) and thrombocytopenia (42%). Non
      survivors had longer PT and aPTT and lower antithrombin (P<0.001) at presentation
      compared to survivors (23.8s vs.10.5; 37.9 vs.17.6s and 5% vs. 54%,
      respectively). Hyperbilirubinaemia (>56.6 MUmol/L) and albumin concentration
      <32.5 g/L at presentation were risk factors for mortality (P<0.0001). Common
      complications included disseminated intravascular coagulation (58%), hepatic
      encephalopathy (35%) and acute kidney injury (4%). The mortality rate was 68%,
      suggesting that dogs with aflatoxicosis have poor prognosis.

PMID- 21875730
TI  - Use of breathing exercises and enforced mobilization after colorectal surgery.

PMID- 21875731
TI  - Single nucleotide polymorphisms and development of hereditary medullary thyroid
      cancer in V804M RET families: disease modification or linkage disequilibrium?

PMID- 21875732
TI  - Oncologic outcomes of pathologic stage I lower rectal cancer with or without
      preoperative chemoradiotherapy: are they comparable?
AB  - BACKGROUND: Good responses (ypStage I) after preoperative chemoradiation therapy
      (CRT) and curative resection for locally advanced rectal cancer are associated
      with excellent local control and improved disease-free survival. This study was
      conducted to evaluate whether this population has comparable oncologic outcomes
      with those for patients with early rectal cancer (pStage I). METHODS: This
      prospective study included 123 patients with pathologic stage I rectal cancer
      that was located less than 7 cm from the anal verge and who underwent radical
      resection. Of the 123 patients, 30 patients underwent preoperative CRT followed
      by radical resection, while 93 underwent proctectomy with no preoperative
      treatment. The oncologic outcomes between the 2 groups were compared. RESULTS:
      The median follow-up period was 78 months. The pretreatment clinical staging was
      significantly different between the 2 groups (P < .001). The 10-year overall and
      disease-free survival rates for the patients who received preoperative CRT were
      48% and 75%, respectively, which were different from the rates for those patients
      who did not undergo preoperative CRT (83%; P = .001 and 93%; P = .001,
      respectively); however, the 10-year local recurrence rates did not significantly
      differ between the patients who received preoperative CRT and those who did not
      receive preoperative CRT (7% vs 5%, respectively, P = .381). CONCLUSION: Good
      responses after preoperative CRT and curative resection for locally advanced
      rectal cancer may be associated with local control that is similar to that of the
      patients with early rectal cancer.

PMID- 21875733
TI  - An increase in the number of predictive factors augments the likelihood of
      malignancy in branch duct intraductal papillary mucinous neoplasm of the
      pancreas.
AB  - BACKGROUND: International consensus guidelines for the management of intraductal
      papillary mucinous neoplasms (IPMNs) of the pancreas provide several factors that
      can be used to predict which IPMNs will become malignant.The sensitivity of each
      factor's predictive accuracy, however, is relatively low, making it difficult to
      determine the appropriate treatment in individual cases. The aim of this study
      was to investigate whether increasing the number of predictive factors might
      augment the sensitivity of the established guidelines to detect malignant IPMNs.
      METHODS: The medical records of 138 patients with IPMNs resected at our
      institution were reviewed. Possible malignant predictors were analyzed by
      univariate and multivariate analysis, and the effects of the number of factors
      and the predictive score of the pathologic results were examined. The cutoff
      points for the number of predictors to discriminate between malignant and
      nonmalignant IPMNs were established by constructing receiver operating
      characteristic curves. RESULTS: A predictive analysis could not be carried out
      for the main duct IPMNs because of the high prevalence of malignancy and the
      small number of significant predictors associated with them. For malignant branch
      duct IPMNs, however, we identified 4 predictive factors that helped determine the
      correct diagnosis as follows: (1) the presence of a cyst >=30 mm in diameter; (2)
      the presence of mural nodules; (3) a history of acute pancreatitis; and (4)
      atypical results of pancreatic juice cytology. An increase in the number of these
      factors significantly affected the sensitivity to predict malignancy. The area
      under the curve for the number of predictors for malignant branch duct IPMNs was
      0.856, and the sensitivity and specificity were 96% and 71%, respectively, when
      the cutoff point was set at 2. The predictive scoring system also showed the same
      values of sensitivity and specificity for the number of factors. CONCLUSION:
      Patients with branch duct IPMNs who have 2 or more of the 4 predictive factors
      described above should undergo standard pancreatectomy with lymph node
      dissection, whereas patients who present with 0 or 1 predictive factor can be
      treated by minimal pancreatectomy without nodal dissection or by careful
      observation without resection. All patients with main duct IPMNs, therefore,
      should be treated with resection as suspected malignancies.

PMID- 21875734
TI  - How best to measure surgical quality? Comparison of the Agency for Healthcare
      Research and Quality Patient Safety Indicators (AHRQ-PSI) and the American
      College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP)
      postoperative adverse events at a single institution.
AB  - BACKGROUND: Evaluating surgical outcomes is an important tool to compare
      providers and institutions and to drive process improvements. Differing
      methodologies, however, may provide conflicting measurements of similar clinical
      outcomes making comparisons difficult. ACS-NSQIP is a validated, risk-adjusted,
      clinically derived data methodology to compare observed to expected outcomes
      after a wide variety of operations. The AHRQ-PSI are a set of computer algorithms
      to identify potential adverse in-patient events using secondary ICD-9-CM
      diagnosis and procedure codes from hospital discharge abstracts. METHODS: We
      compared the ACS-NSQIP and AHRQ-PSI methods for hospital general surgical (n =
      6565) or vascular surgical inpatients procedures (n = 1041) at a tertiary-care
      academic institution from April 2006 to June 2009 on 7 adverse event types.
      RESULTS: ACS-NSQIP inpatient adverse events were identified in 564 (7.4%)
      patients. AHRQ-PSIs were identified in 268 (3.5%) patients. Only 159 (2.1%)
      patients had inpatient events identified by both methods. Using ACS-NSQIP as the
      clinically based standard the sensitivity of the specific AHRQ-PSI ranged from
      0.030 for infections to 0.535 for PE/DVT. Positive predictive values of AHRQ-PSI
      ranged from 18% for hemorrhage/hematoma to 89% for renal failure. Greater
      agreement at greater ASA class and wound classification was observed. CONCLUSION:
      AHRQ-PSI algorithms identified less than a third of the ACS-NSQIP clinically
      important adverse events. Furthermore, the AHRQ-PSI identified a large number of
      events with no corresponding clinically important adverse outcomes. The
      sensitivity of the AHRQ-PSI for detecting clinically relevant adverse events
      identified by the ACS-NSQIP varied widely. The AHRQ-PSI as applied to
      postoperative patients is a poor measure of quality performance.

PMID- 21875735
TI  - Matrix metalloproteinase-8 overexpression prevents proper tissue repair.
AB  - BACKGROUND: The collagenolytic matrix metalloproteinase-8 (MMP-8) is essential
      for normal tissue repair but is often overexpressed in wounds with disrupted
      healing. Our aim was to study the impact of a local excess of this neutrophil
      derived proteinase on wound healing using recombinant adenovirus-driven
      transduction of full-length Mmp8 (AdMMP-8). METHODS: The effect of MMP-8
      overexpression was evaluated in dermal fibroblasts and in two wound healing
      models in male Wistar rats: subcutaneously positioned ePTFE catheters and linear
      incisional skin wounds. RESULTS: Fibroblasts transduced with AdMMP-8 secreted MMP
      8 with type I collagenolytic activity that could be blocked by a selective MMP-8
      inhibitor. AdMMP-8 (5 * 10(10) viral particles) administered in homologous fibrin
      increased MMP-8 mRNA (P < .05) levels compared to parallel wounds treated with a
      control adenovirus expressing lacZ (AdLacZ). Impaired wound healing was
      demonstrated with AdMMP-8 by decreased collagen deposition and breaking strength
      of incisional wounds on day 7 compared to AdLacZ-treated wounds (P < .05). We
      found no significant effect of AdMMP-8 on mRNA levels of MMP-9, COL1A1, or
      COL3A1, but AdMMP-8 treatment decreased the number of neutrophils. In the
      incisional wounds, MMP-8 gene transfer was not associated with significant
      changes in macrophage numbers or amount of granulation tissue but did increase
      MMP-8 protein by 76% (P < .01) and decrease type I collagen protein by 29% (P <
      .05) compared with AdLacZ. CONCLUSION: These results demonstrate that
      superphysiologic levels of the proteinase MMP-8 can result in decreased collagen
      and lead to impaired wound healing. This observation makes MMP-8 a potential drug
      target in compromised human wound healing associated with MMP-8 overexpression.

PMID- 21875736
TI  - Gallbladder calcification leads to discovery of carcinosarcoma of the
      gallbladder.

PMID- 21875737
TI  - Mycotic aneurysm of the superior mesenteric artery.

PMID- 21875738
TI  - Bromate formation in a hybrid ozonation-ceramic membrane filtration system.
AB  - The effect of pH, ozone mass injection rate, initial bromide concentration, and
      membrane molecular weight cut off (MWCO) on bromate formation in a hybrid
      membrane filtration-ozonation reactor was studied. Decreasing the pH,
      significantly reduced bromate formation. Bromate formation increased with
      increasing gaseous ozone mass injection rate, due to increase in dissolved ozone
      concentrations. Greater initial bromide concentrations resulted in higher bromate
      concentrations. An increase in the bromate concentration was observed by reducing
      MWCO, which resulted in a concomitant increase in the retention time in the
      system. A model to estimate the rate of bromate formation was developed. Good
      correlation between the model simulation and the experimental data was achieved.

PMID- 21875739
TI  - Fine-scale bacterial community dynamics and the taxa-time relationship within a
      full-scale activated sludge bioreactor.
AB  - In activated sludge bioreactors, aerobic heterotrophic communities efficiently
      remove organics, nutrients, toxic substances, and pathogens from wastewater, but
      the dynamics of these communities are as yet poorly understood. A macroecology
      metric used to quantify community shifts is the taxa-time relationship, a
      temporal analog of the species-area curve. To determine whether this metric can
      be applied to full-scale bioreactors, activated sludge samples were collected
      weekly over a one-year period at a local municipal wastewater treatment plant.
      Bacterial community dynamics were evaluated by monitoring 16S rRNA genes using
      Terminal Restriction Fragment Length Polymorphism (T-RFLP), corroborated by clone
      libraries. Observed taxa richness increased with time according to a power law
      model, as predicted by macroecological theory, with a power law exponent of w =
      0.209. The results reveal strong long-term temporal dynamics during a period of
      stable performance (BOD removal and nitrification). Community dynamics followed a
      gradual succession away from initial conditions rather than periodicity around a
      mean "equilibrium", with greater within-month then among-month community
      similarities. Changes in community structure were significantly associated via
      multivariate statistical analyses with dissolved oxygen, temperature, influent
      silver, biomass (MLSS), flow rate, and influent nitrite, cadmium and chromium
      concentrations. Overall, our results suggest patterns of bacterial community
      dynamics likely regulated in part by operational parameters and provide evidence
      that the taxa-time relationship may be a fundamental ecological pattern in macro-
      and microbial systems.

PMID- 21875740
TI  - Theoretical evaluation of the configurations and Raman spectra of 209
      polychlorinated biphenyl congeners.
AB  - Though polychlorinated biphenyls (PCBs) have distributed as threats in the
      environment to human beings for several decades, monitoring of trace level PCBs
      in-field is still a challenge. As a potential method for monitoring PCBs at trace
      levels, Raman spectroscopy has been used to detect several PCBs in the
      laboratory. To facilitate the development of rapid detection of PCBs by Raman
      spectroscopy, it is essential to investigate the Raman spectra of all PCB
      congeners. Herein, the stable configurations and vibrational spectra of all the
      PCB congeners were calculated by Gaussian 03 program package. Based on molecular
      symmetry, PCBs are classified into seven groups. The structural features and the
      normal vibration modes for each group are discussed. Taking the C(2)-2 group as
      an example, the wavenumber ranges of the various normal vibration modes in the
      Raman spectra of PCBs were analyzed. The accuracy of calculated results was
      verified by experimental Raman spectra of PCB77 standard. This study can
      elucidate further information to promote the development of Raman spectroscopy in
      environmental monitoring.

PMID- 21875741
TI  - Can time-weighted average concentrations be used to assess the risks of
      metsulfuron-methyl to Myriophyllum spicatum under different time-variable
      exposure regimes?
AB  - We tested the effects of the herbicide metsulfuron-methyl on growth of the
      submerged macrophyte Myriophyllum spicatum under laboratory conditions using
      different exposure scenarios. The exposures of each scenario were comparable in
      the concentration * time factor, viz., the same 21-d time-weighted average (TWA)
      concentrations but variable in peak exposure concentrations (ranging from 0.1 to
      21000 ng ai L-1) and exposure periods (1, 3, 7, 14 or 21 d). To study recovery
      potential of the exposed M. spicatum plants we continued the observation on shoot
      and root growth for another 21 d in herbicide-free medium so that the total
      observation period was 42 d. Non-destructive endpoints, length and number of new
      shoots and roots, were determined weekly from day 14 onwards. Destructive
      endpoints, dry-weight (DW) of main shoots, new shoots and new roots, were
      measured at the end of the experiment (t=42 d). Metsulfuron-methyl exposure in
      particular inhibited new tissue formation but was not lethal to main shoots. On
      days 21 and 42 after start exposure, EC10/EC50 values for new tissues expressed
      in terms of peak concentration (=measured concentration during exposure periods
      of different length) showed large differences between exposure scenarios in
      contrast to EC10/EC50 values for days 21 and 42 expressed in terms of 21-d and 42
      d TWA concentrations, respectively. At the end of the experiment (day 42), 42-d
      TWA EC(x) values were remarkably similar between exposure scenarios, while a
      similar trend could already be observed on day 21 for 21-d TWA EC(x) values. For
      the macrophyte M. spicatum and exposure to the herbicide metsulfuron-methyl the
      TWA approach seems to be appropriate to use in the risk assessment. However, the
      data from the toxicity experiment suggest that on day 21 also the absolute height
      of the pulse exposure played a (minor) role in the exposure - response
      relationships observed.

PMID- 21875742
TI  - Rituximab therapy in refractory neuropsychiatric lupus: current clinical
      evidence.
AB  - OBJECTIVE: To review and summarize published information on the effectiveness and
      safety of rituximab (RTX) in adult patients with refractory neuropsychiatric
      systemic lupus erythematosus (NPSLE). METHODS: We describe a patient with
      persistently active NPSLE, despite conventional therapy, who responded
      dramatically to RTX. Current evidence on the therapeutic use of RTX in this
      complex situation is also analyzed through a systematic review of the English
      language literature, based on a PubMed search. RESULTS: Available data on the use
      of RTX in refractory NPSLE come from a large number of case reports and some open
      label studies. Including our case, 35 patients have been well documented. A
      complete or partial therapeutic response was achieved in 85% of patients after 1
      cycle of treatment. A positive correlation between serological markers of disease
      activity and clinical outcome has also been demonstrated in some of these
      patients. Clinical improvement was accompanied by a significant reduction in the
      daily dose of oral corticosteroids. Relapse after RTX treatment was noted in 45%
      of cases (median 9.5 months; range, 4-33 months). Infections were observed in 29%
      of patients. CONCLUSION: Evidence for the effectiveness of RTX as induction
      therapy in NPSLE is based solely on several case reports and noncontrolled
      trials. Although it is not yet possible to make definite recommendations, the
      global analysis of these cases supports the off-label use of RTX in cases of
      severe refractory NPSLE.

PMID- 21875743
TI  - Tamoxifen promotes superoxide production in platelets by activation of PI3-kinase
      and NADPH oxidase pathways.
AB  - BACKGROUND: Tamoxifen is a selective estrogen receptor antagonist that is widely
      used for treatment and prevention of breast cancer. However, tamoxifen use can
      lead to an increased incidence of thrombotic events. The reason for this adverse
      event remains unknown. Previous studies showed that tamoxifen and its active
      metabolite Z-4-hydroxytamoxifen rapidly increased intracellular free calcium
      ([Ca(2+)](i)) in human platelets by a non-genomic mechanism that involved the
      activation of phospholipase C. Platelets play a pivotal role in thrombosis and
      Ca(2+) elevation is a central event in platelet activation. Therefore the
      mechanism by which tamoxifen activated Ca(2+) entry into platelets was
      investigated. METHODS: [Ca(2+)](i) was measured using the fluorescent indicator
      fura-2 and reactive oxygen species were measured using lucigenin in isolated
      human platelets. RESULTS: Tamoxifen analogs E-4-hydroxytamoxifen, with weak
      activity at the nuclear estrogen receptor and Z-4-hydroxytamoxifen, with strong
      activity at nuclear estrogen receptor, were equally active at increasing
      [Ca(2+)](i) and synergizing with ADP and thrombin to increase [Ca(2+)](i) in
      platelets. This result suggests that the effects of tamoxifen and E- and Z-4
      hydroxytamoxifen to increase [Ca(2+)](i) are not mediated by the classical
      genomic estrogen receptor. The effects of tamoxifen to increase [Ca(2+)](i) were
      strongly inhibited by apocynin and apocynin dimer. This suggests that tamoxifen
      activates NADPH oxidase which leads to superoxide generation and in turn caused
      an increase in [Ca(2+)](i). Free radical scavengers TEMPO and TEMPOL also
      inhibited tamoxifen-induced [Ca(2+)](i) elevation. Inhibition of phosphoinositide
      3-kinase (PI3-kinase), an upstream effector of NADPH oxidase with wortmannin and
      LY-294,002 also caused substantial inhibition of tamoxifen-induced elevation of
      [Ca(2+)](i). CONCLUSION: Tamoxifen increases [Ca(2+)](i) in human platelets by a
      non-genomic mechanism. Tamoxifen activates phospholipase Cgamma as well as PI3
      kinase and NADPH oxidase pathway to generate superoxide which causes the release
      of Ca(2+) from the endoplasmic reticulum, and promotes Ca(2+) influx into the
      platelets.

PMID- 21875745
TI  - Asthma diagnosis and treatment: filling in the information gaps.
AB  - Current approaches to the diagnosis and management of asthma are based on
      guideline recommendations, which have provided a framework for the efforts.
      Asthma, however, is emerging as a heterogeneous disease, and these features need
      to be considered in both the diagnosis and management of this disease in
      individual patients. These diverse or phenotypic features add complexity to the
      diagnosis of asthma, as well as attempts to achieve control with treatment.
      Although the diagnosis of asthma is often based on clinical information, it is
      important to pursue objective criteria as well, including an evaluation for
      reversibility of airflow obstruction and bronchial hyperresponsiveness, an area
      with new diagnostic approaches. Furthermore, there exist a number of treatment
      gaps (ie, exacerbations, step-down care, use of antibiotics, and severe disease)
      in which new direction is needed to improve care. A major morbidity in asthmatic
      patients occurs with exacerbations and in patients with severe disease. Novel
      approaches to treatment for these conditions will be an important advance to
      reduce the morbidity associated with asthma.

PMID- 21875744
TI  - The protective effect of farm milk consumption on childhood asthma and atopy: the
      GABRIELA study.
AB  - BACKGROUND: Farm milk consumption has been identified as an exposure that might
      contribute to the protective effect of farm life on childhood asthma and
      allergies. The mechanism of action and the role of particular constituents of
      farm milk, however, are not yet clear. OBJECTIVE: We sought to investigate the
      farm milk effect and determine responsible milk constituents. METHODS: In rural
      regions of Germany, Austria, and Switzerland, a comprehensive questionnaire about
      farm milk consumption and other farm-related exposures was completed by parents
      of 8334 school-aged children, and 7606 of them provided serum samples to assess
      specific IgE levels. In 800 cow's milk samples collected at the participants'
      homes, viable bacterial counts, whey protein levels, and total fat content were
      analyzed. Asthma, atopy, and hay fever were associated to reported milk
      consumption and for the first time to objectively measured milk constituents by
      using multiple regression analyses. RESULTS: Reported raw milk consumption was
      inversely associated to asthma (adjusted odds ratio [aOR], 0.59; 95% CI, 0.46
      0.74), atopy (aOR, 0.74; 95% CI, 0.61-0.90), and hay fever (aOR, 0.51; 95% CI,
      0.37-0.69) independent of other farm exposures. Boiled farm milk did not show a
      protective effect. Total viable bacterial counts and total fat content of milk
      were not significantly related to asthma or atopy. Increased levels of the whey
      proteins BSA (aOR for highest vs lowest levels and asthma, 0.53; 95% CI, 0.30
      0.97), alpha-lactalbumin (aOR for interquartile range and asthma, 0.71; 95% CI,
      0.52-0.97), and beta-lactoglobulin (aOR for interquartile range and asthma, 0.62;
      95% CI, 0.39-0.97), however, were inversely associated with asthma but not with
      atopy. CONCLUSIONS: The findings suggest that the protective effect of raw milk
      consumption on asthma might be associated with the whey protein fraction of milk.

PMID- 21875746
TI  - How much of the farming effect is environmental?

PMID- 21875747
TI  - Unique relations of age and delinquency with cognitive control.
AB  - Context processing has significant empirical support as an explanation of age-
      and psychopathology-related deficiencies in cognitive control. We examined
      whether context processing generalizes to younger individuals who are in trouble
      with the law. We tested whether age and delinquency might have unique relations
      to context processing skills in four samples of male participants: adolescent
      offenders (n = 43), control adolescents (n = 33), young adult offenders (n = 40),
      and control young adults (n = 31). We used a modified Stroop task to measure
      context processing (i.e., attention, memory, and response inhibition). Task
      performance was superior for older participants in conditions most demanding of
      context processing skills. Adolescent offenders and control adolescents showed
      difficulties engaging selective attention to filter out irrelevant information,
      even after controlling for the effects of age. Control adolescents made the most
      errors in the condition most demanding of context processing, whereas the other
      three samples showed slower processing but fewer errors in context processing.

PMID- 21875748
TI  - The photoluminescence, drug delivery and imaging properties of multifunctional
      Eu3+/Gd3+ dual-doped hydroxyapatite nanorods.
AB  - The design and synthesis of multifunctional systems with high biocompatibility
      are very significant for the future of clinical applications. Herein, we report a
      microwave-assisted rapid synthesis of multifunctional Eu(3+)/Gd(3+) dual-doped
      hydroxyapatite (HAp) nanorods, and the photoluminescence (PL), drug delivery and
      in vivo imaging of as-prepared Eu(3+)/Gd(3+) doped HAp nanorods. The
      photoluminescent and magnetic multifunctions of HAp nanorods are realized by the
      dual-doping with Eu(3+) and Gd(3+). The PL intensity of doped HAp nanorods can be
      adjusted by varying Eu(3+) and Gd(3+) concentrations. The magnetization of doped
      HAp nanorods increases with the concentration of doped Gd(3+). The as-prepared
      Eu(3+)/Gd(3+)-doped HAp nanorods exhibit inappreciable toxicity to the cells in
      vitro. More importantly, the Eu(3+)/Gd(3+)-doped HAp nanorods show a high drug
      adsorption capacity and sustained drug release using ibuprofen as a model drug,
      and the drug release is governed by a diffusion process. Furthermore, the
      noninvasive visualization of nude mice with subcutaneous injection indicates that
      the Eu(3+)/Gd(3+)-doped HAp nanorods with the photoluminescent function are
      suitable for in vivo imaging. In vitro and in vivo imaging tests indicate that
      Eu(3+)/Gd(3+)-doped HAp nanorods have a potential in applications such as a
      multiple-model imaging agent for magnetic resonance (MR) imaging,
      photoluminescence imaging and computed tomography (CT) imaging. The Eu(3+)/Gd(3+)
      dual-doped HAp nanorods are promising for applications in the biomedical fields
      such as multifunctional drug delivery systems with imaging guidance.

PMID- 21875749
TI  - Growth promoting substrates for human dermal fibroblasts provided by artificial
      extracellular matrices composed of collagen I and sulfated glycosaminoglycans.
AB  - The application of native extracellular matrix (ECM) components is a promising
      approach for biomaterial design. Here, we investigated artificial ECM (aECM)
      consisting of collagen I (coll) and the glycosaminoglycans (GAGs) hyaluronan (HA)
      or chondroitin sulfate (CS). Additionally, GAGs were chemically modified by the
      introduction of sulfate groups to obtain low-sulfated and high-sulfated GAG
      derivatives. Sulfate groups are expected to bind and concentrate growth factors
      and improve their bioactivity. In this study we analyzed the effect of aECM on
      initial adhesion, proliferation, ECM synthesis and differentiation of human
      dermal fibroblasts (dFb) within 8-48 h. We show that initial adhesion and cell
      proliferation of dFb progressively increased in a sulfate dependent manner. In
      contrast, synthesis of ECM components coll and HA was decreased on high-sulfated
      aECM coll/HA3.0 and coll/CS3.1. Furthermore, the matrix metallo-proteinase-1 (MMP
      1) was down-regulated on coll/HA3.0 and coll/CS3.1 on mRNA and protein level. The
      fibroblast differentiation marker alpha-smooth muscle actin (alphaSMA) is not
      affected by aECM on mRNA level. Artificial ECM consisting of coll and high
      sulfated GAGs proves to be a suitable biomaterial for dFb adhesion and
      proliferation that induces a "proliferative phenotype" of dFb found in the early
      stages of cutaneous wound healing.

PMID- 21875750
TI  - Conatumumab (AMG 655) coated nanoparticles for targeted pro-apoptotic drug
      delivery.
AB  - Colloidal nanoparticle drug delivery systems have attracted much interest for
      their ability to enable effective formulation and delivery of therapeutic agents.
      The selective delivery of these nanoparticles to the disease site can be enhanced
      by coating the surface of the nanoparticles with targeting moieties, such as
      antibodies. In this current work, we demonstrate that antibodies on the surface
      of the particles can also elicit key biological effects. Specifically, we
      demonstrate the induction of apoptosis in colorectal HCT116 cancer cells using
      PLGA nanoparticles coated with Conatumumab (AMG 655) death receptor 5-specific
      antibodies (DR5-NP). We show that DR5-NP preferentially target DR5-expressing
      cells and present a sufficient density of antibody paratopes to induce apoptosis
      via DR5, unlike free AMG 655 or non-targeted control nanoparticles. We also
      demonstrate that DR5-targeted nanoparticles encapsulating the cytotoxic drug
      camptothecin are effectively targeted to the tumour cells, thereby producing
      enhanced cytotoxic effects through simultaneous drug delivery and apoptosis
      induction. These results demonstrate that antibodies on nanoparticulate surfaces
      can be exploited for dual modes of action to enhance the therapeutic utility of
      the modality.

PMID- 21875752
TI  - Intensity dependent repetitive transcranial magnetic stimulation modulation of
      blood oxygenation.
AB  - BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is increasingly
      being investigated in clinical settings for the treatment of neurological and
      psychiatric disorders such as dystonia, schizophrenia, and major depressive
      disorder (MDD). Using near infra-red spectroscopy (NIRS), very short trains of
      rTMS have previously been shown to modulate cortical blood oxygenation. METHODS:
      In order to investigate the effect of longer, clinically relevant trains of 1 Hz
      rTMS on oxy-hemoglobin (HbO) at prefrontal cortex, the current study applied ten
      minute trains of rTMS at both subthreshold and suprathreshold intensities.
      RESULTS: A similar profile of oxygenation change was observed during the
      beginning 30-40 s of the trains, however for the remainder, subthreshold rTMS
      returned to baseline while the suprathreshold TMS resulted in a long period of
      reduced oxygenation. LIMITATIONS: Small sample size. CONCLUSIONS: The differences
      observed may be a product of changes in HbO requirements by inhibitory/excitatory
      neural circuits, either by reduced HbO demand or by increased HbO consumption,
      while sustained HbO reduction may be a consequence of a modulation of vaso-motor
      reactivity. This study has implications for understanding the mechanisms involved
      in the physiological changes evoked by rTMS and efficacious clinical application
      of rTMS in disorders such as MDD.

PMID- 21875751
TI  - Inhibition of the transport of HIV in vitro using a pH-responsive synthetic mucin
      like polymer system.
AB  - In conjunction with the routine role of delivering the active ingredient,
      carefully designed drug delivery vehicles can also provide ancillary functions
      that augment the overall efficacy of the system. Inspired by the ability of the
      cervicovaginal mucus to impede the movement of HIV virions at acidic pH, we have
      engineered a pH-responsive synthetic polymer that shows improved barrier
      properties over the naturally occurring cervicovaginal mucus by inhibiting viral
      transport at both acidic and neutral pH. The pH-responsive synthetic mucin-like
      polymer is constructed with phenylboronic acid (PBA) and salicylhydroxamic acid
      (SHA), each individually copolymerized with a 2-hydroxypropyl methacrylamide
      (pHPMA) polymer backbone. At pH 4.8, the crosslinked polymers form a transient
      network with a characteristic relaxation time of 0.9 s and elastic modulus of 11
      Pa. On addition of semen, the polymers form a densely crosslinked elastic network
      with a characteristic relaxation time greater than 60 s and elastic modulus of
      1800 Pa. Interactions between the PBA-SHA crosslinked polymers and mucin at
      acidic pH showed a significant increase in elastic modulus and crosslink lifetime
      (p < 0.05). A transport assay revealed that migration of HIV and cells was
      significantly impeded by the polymer network at pH >= 4.8 with a diffusion
      coefficient of 1.60 x 10(-4) MUm(2)/s for HIV. Additionally, these crosslinked
      polymers did not induce symptoms of toxicity or irritation in either human
      vaginal explants or a mouse model. In summary, the pH-responsive crosslinked
      polymer system reported here holds promise as a class of microbicide delivery
      vehicle that could inhibit the transport of virions from semen to the target
      tissue and, thereby, contribute to the overall activity of the microbicide
      formulation.

PMID- 21875753
TI  - Seasonality of suicide in Shandong China, 1991-2009: associations with gender,
      age, area and methods of suicide.
AB  - BACKGROUNDS: Whether suicide in China has significant seasonal variations is
      unclear. The aim of this study is to examine the seasonality of suicide in
      Shandong China and to assess the associations of suicide seasonality with gender,
      residence, age and methods of suicide. METHODS: Three types of tests (Chi-square,
      Edwards' T and Roger's Log method) were used to detect the seasonality of the
      suicide data extracted from the official mortality data of Shandong Disease
      Surveillance Point (DSP) system. Peak/low ratios (PLRs) and 95% confidence
      intervals (CIs) were calculated to indicate the magnitude of seasonality.
      RESULTS: A statistically significant seasonality with a single peak in suicide
      rates in spring and early summer, and a dip in winter was observed, which
      remained relatively consistent over years. Regardless of gender, suicide
      seasonality was more pronounced in rural areas, younger age groups and for non
      violent methods, in particular, self-poisoning by pesticide. CONCLUSIONS: There
      are statistically significant seasonal variations of completed suicide for both
      men and women in Shandong, China. Differences exist between residence
      (urban/rural), age groups and suicide methods. Results appear to support a
      sociological explanation of suicide seasonality.

PMID- 21875754
TI  - Anti-neuronal and stress-induced-phosphoprotein 1 antibodies in neuro-Behcet's
      disease.
AB  - No disease-specific neuronal antibodies have so far been defined in neuro
      Behcet's disease (NBD). Immunohistochemistry and immunocytochemistry studies
      showed antibodies to hippocampal and cerebellar molecular layers and the surface
      antigens of cultured hippocampal neurons in sera and/or cerebrospinal fluids
      (CSF) of 13 of 20 NBD and 6 of 20 BD patients but not in multiple sclerosis or
      headache controls. Screening with a protein macroarray led to identification of
      stress-induced-phosphoprotein-1 (STIP-1) as an antigenic target. High-titer STIP
      1-antibodies were detected in 6 NBD patients' sera but not in controls. These
      results suggest that neuronal antibodies could be useful as diagnostic biomarkers
      in NBD.

PMID- 21875755
TI  - Intracoronary ECG during primary percutaneous coronary intervention for ST
      segment elevation myocardial infarction predicts microvascular obstruction and
      infarct size.
AB  - INTRODUCTION: Microvascular obstruction (MVO) following ST-segment elevation
      myocardial infarction (STEMI) is associated with larger infarct size and an
      increased mortality. Although angiographic predictors of MVO in primary
      percutaneous coronary intervention (primary-PCI) setting have been identified, an
      earlier and objective "in-lab" predictor may be beneficial, in order to
      potentially influence therapies administered during primary-PCI. We hypothesised
      that intracoronary-electrocardiogram (IC-ECG) is a simple, objective and accurate
      predictor of MVO evaluated by cardiac magnetic resonance (CMR) and is comparable
      to myocardial blush grade (MBG) and TIMI myocardial perfusion grade (TMPG).
      METHOD: Intracoronary ECG was performed during primary-PCI. Intracoronary ST
      segment measurement was performed before and immediately after opening of infarct
      related-artery. Intracoronary ST-segment resolution (IC-STR) was defined as >= 1
      mm improvement compared to baseline. Contrast enhanced CMR was performed at 4 and
      90 days post primary-PCI. Primary endpoint was MVO on late gadolinium
      hyperenhancement assessed by CMR at day 4. RESULTS: Sixty-four consecutive
      patients (age 59 +/- 11 years; 55 males) were recruited. Intracoronary ST-segment
      resolution correlated with MVO (p=0.005). Furthermore, IC-STR correlated with
      infarct-mass, non-viable-mass, peak creatinine kinase and end-systolic-volume at
      day 4. Intracoronary ST-segment resolution also correlated with favourable left
      ventricular end-diastolic-volume at day 90 (p=0.022). On multivariate analysis,
      IC-STR was an independent predictor of MVO. CONCLUSION: Intracoronary ST-segment
      resolution is a strong in-lab predictor of MVO assessed 4 days after STEMI on
      CMR. Furthermore, IC-STR correlates with infarct size and left ventricular
      remodelling at 3 months. Further studies are required to understand potential
      clinical utility of this tool.

PMID- 21875756
TI  - Measuring scapular kinematics during arm lowering using the acromion marker
      cluster.
AB  - The aim of the present study was to examine the acromion marker cluster (AMC)
      method of measuring scapular kinematics during the arm lowering, eccentric,
      phase. Twenty six participants completed arm elevation and lowering in the
      sagittal, frontal and scapular plane. The participants held their arm at 30
      degrees  increments while the orientation of the scapula was recorded using an
      AMC and a scapular locator (SL). There were no significant differences between
      the AMC and SL during the lowering phase for sagittal and scapular plane arm
      movements. The AMC significantly underestimated upward rotation (max RMSE = 6.0
      degrees ), and significantly overestimated posterior tilt (max RMSE = 7.2 degrees
      ) during arm lowering in the frontal plane. The reported root mean square errors,
      however, were within the ranges observed during the elevation phase and reported
      in previous literature. The AMC therefore provides a reasonable description of
      scapular kinematics during the arm lowering phase.

PMID- 21875757
TI  - The physiologic and phenotypic alterations due to macrolide exposure in
      Campylobacter jejuni.
AB  - Physiologic and phenotypic alterations in the context of antibiotic resistance
      have been extensively studied in some bacteria. However there are not enough data
      addressing these alterations due to macrolide resistance in Campylobacter jejuni.
      The present study examined the fitness cost imposed by different macrolide
      resistance mutations and the phenotypic alterations due to exposure to macrolides
      in C. jejuni. C. jejuni was induced with different macrolide agents to obtain
      different macrolide resistance mutations. The results revealed that the mutations
      significantly imposed defect variations on the doubling time and the relative
      fitness in the resistant strains when competed against the susceptible strain.
      Furthermore macrolides through induction or exposure to sub-MIC concentrations
      impaired the motility of C. jejuni in 0.4% MH agar plates. Electron microscope
      analysis revealed the absence of flagellar filaments from strains exposed to
      macrolides. SDS-PAGE demonstrated that macrolides have no effect on protein
      synthesis and immunoblotting analysis further confirmed that flagellin was fully
      synthesized within C. jejuni strains exposed to macrolides. Nevertheless C.
      jejuni strains exposed to macrolides demonstrated defect in their excreted
      flagellin into the supernatant compared to strains not exposed to macrolides.
      Accordingly we speculated that macrolides inhibited flagellar filament formation
      in the strains exposed to macrolides via affecting the secretion of flagellin
      without affecting the amount synthesized within the bacteria. Taken together
      these findings demonstrated that different macrolide resistance mutations imposed
      different fitness costs and exposure to macrolides resulted in phenotypic
      alterations such as inhibition of flagellar filament formation and loss of
      motility in C. jejuni.

PMID- 21875758
TI  - A randomized double-blind placebo-controlled pilot study to assess the efficacy
      of a 24-week topical treatment by latanoprost 0.1% on hair growth and
      pigmentation in healthy volunteers with androgenetic alopecia.
AB  - BACKGROUND: Latanoprost is a prostaglandin analogue used to treat glaucoma. It
      can cause adverse effects, such as iridial and periocular hyperpigmentation, and
      eyelash changes including pigmentation and increased thickness, length, and
      number. Latanoprost has been used to treat eyelash alopecia, but knowledge on its
      effects on human scalp hair growth is not available. OBJECTIVE: The primary
      objectives were to assess the efficacy of latanoprost on hair growth and
      pigmentation. The secondary objectives were to assess the effect on scalp
      pigmentation; investigate the treatment duration needed to affect hair growth,
      hair pigmentation, and scalp pigmentation; and assess safety of latanoprost.
      METHODS: Sixteen men with mild androgenetic alopecia (Hamilton II-III) were
      included. Latanoprost 0.1% and placebo were applied daily for 24 weeks on two
      minizones on the scalp. Measurements on hair growth, density, diameter,
      pigmentation, and anagen/telogen ratio were performed throughout the study.
      RESULTS: At 24 weeks, an increased hair density on the latanoprost-treated site
      was observed compared with baseline (n = 16, P < .001) and placebo-treated site
      (P = .0004). LIMITATIONS: Only young men with mild androgenetic alopecia were
      included. The results may not be applicable to other patient groups. Choice of
      investigational site may have affected the results. CONCLUSIONS: Latanoprost
      significantly increased hair density (terminal and vellus hairs) at 24 weeks
      compared with baseline and the placebo-treated area. Latanoprost could be useful
      in stimulating hair follicle activity and treating hair loss.

PMID- 21875759
TI  - Basal cell carcinoma on the ear is more likely to be of an aggressive phenotype
      in both men and women.
AB  - BACKGROUND: We observed that basal cell carcinoma (BCC) on the ear demonstrates a
      more aggressive phenotype compared with other body sites. OBJECTIVE: We sought to
      determine if it is statistically significant that BCC on the ear is more
      aggressive. METHODS: We queried our 2009 database for all BCCs biopsied from the
      ear. Multiple data points, including tumor subtype and risk level, were analyzed
      for 100 BCCs on the ear and 100 BCCs on the cheek. RESULTS: BCC on the ear was
      diagnosed 471 times. Of the first 100 occurrences of BCC on the ear, 57% were
      high risk compared with 38% on the cheek (odds ratio 2.16, 95% confidence
      interval 1.23-3.81, P = .01). Men were more likely to have BCC on the ear: 79%
      male on the ear and 53% male on the cheek (P < .001). However, BCC on the ear in
      women is also more likely to be aggressive (57%, 12 of 21). LIMITATIONS: The data
      were retrieved from a single year at our institution, and there could potentially
      be regional bias given that the population of data is from a single institution.
      Many of the specimens we evaluate are reviewed in consultation and may thus
      represent a selection bias. CONCLUSION: BCC on the ear presents as an aggressive
      phenotype in the majority of cases for both men and women, and it occurs much
      more frequently in men. Knowledge of this information can help guide physicians
      and ensure that these tumors are adequately biopsied and treated.

PMID- 21875761
TI  - Gifts to physicians from industry: the debate evolves.
AB  - In October 2009, the board of directors of the American College of Emergency
      Physicians (ACEP) approved a major revision to ACEP's "Gifts to Emergency
      Physicians from Industry" policy. The revised policy is a response to increasing
      debate and calls for restriction of the long-standing biomedical industry
      practice of giving promotional gifts to individual physicians. This article
      outlines the history of professional attention to gift giving and reviews recent
      contributions to the ongoing debate over its justifiability, including
      professional association recommendations for limitation or prohibition of the
      practice. The article concludes with a description of the provisions of the
      revised ACEP gifts policy and brief reflection on the future of this practice.

PMID- 21875760
TI  - Skin cancer risk perceptions: a comparison across ethnicity, age, education,
      gender, and income.
AB  - BACKGROUND: Studies of noncutaneous and cutaneous malignancies support the
      hypothesis that poor risk-perception status contributes to health disparity.
      OBJECTIVE: We evaluated skin cancer (SC) risk perceptions across race and other
      demographic markers using the Health Information National Trends Survey (HINTS)
      and compared them to discover differences in perception that may contribute to
      the disparities in SC diagnosis and treatment. METHODS: Respondents with no
      history of SC were randomly selected to answer questions assessing perceived risk
      and knowledge of preventive strategies of SC. Logistic regression was performed
      to identify associations between perceptions of SC and demographic variables
      including self-described race, age, sex, education, income, and health insurance
      status. RESULTS: Blacks, the elderly, and people with less education perceived
      themselves as at lower risk of developing SC. They, along with Hispanics, were
      also more likely to believe that one cannot lower their SC risk and that there
      are so many different recommendations on how to prevent SC that it makes it
      difficult to know which ones to follow. Lower education also correlated with
      greater reluctance to have a skin examination. LIMITATIONS: HINTS is a cross
      sectional instrument, thus it only provides a snapshot of SC perceptions.
      CONCLUSION: Uncertainty and altered perceptions are more common in the SC risk
      perceptions of ethnic minorities, the elderly, and those with less education.
      These are the same groups that are subject to disparities in SC outcomes.
      Educational programs directed at these demographic groups may help to reduce the
      SC-related health disparities.

PMID- 21875762
TI  - Influence of chirality of V(V) Schiff base complexes on DNA, BSA binding and
      cleavage activity.
AB  - New chiral V(V) Schiff base complexes (S)-[VO(OMe)L] and (R)-[VO(OMe)L] were
      synthesized and characterized by microanalysis, infrared (IR), UV-Visible,
      Circular dichroism (CD) spectroscopy and single crystal X-ray studies. The
      interaction of these complexes with calf thymus (CT) DNA and bovine serum albumin
      (BSA) protein showed chiral expression DNA/protein binding strength. The
      influence of chirality was also observed in cytotoxicity assay of Hep 2 cells.
      (R)-[VO(OMe)L] enantiomer exhibited higher binding constant (5 +/- 1 * 10(5) M(
      1)) as compared to (S)-[VO(OMe)L] (8 +/- 1 * 10(4) M(-1)). The fluorescence
      quenching, thermal melting and viscosity data suggest DNA surface and/or groove
      binding nature of the complexes and electrophoresis studies also showed greater
      activity for (R)-[VO(OMe)L] in cleaving DNA and protein as against (S)
      [VO(OMe)L].

PMID- 21875763
TI  - Ruthenium(II) phosphine/diimine/picolinate complexes: inorganic compounds as
      agents against tuberculosis.
AB  - This paper describes the synthesis and characterization of four new ruthenium
      complexes containing 1,4 bis(diphenylphosphino)butane (dppb), 2
      pyridinecarboxylic acid anion (pic) and the diimines [(2,2'-bipyridine (bipy),
      4,4'-dimethyl-2,2'-bipyridine (Me-bipy), 4,4'-dichloro-2,2'-bipyridine (Cl-bipy)
      and 1,10-phenanthroline (phen) as ligands, with formulae
      [Ru(pic)(dppb)(bipy)]PF(6) (SCAR01), [Ru(pic)(dppb)(Me-bipy)]PF(6) (SCAR02),
      [Ru(pic)(dppb)(Cl-bipy)]PF(6) (SCAR03) and [Ru(pic)(dppb)(phen)]PF(6) (SCAR04).
      Additionally, the in vitro anti-Mycobacterium tuberculosis (MTB) activity,
      cytotoxicity and activity against in vitro infection of these complexes and two
      more complexes, cis-[Ru(pic)(dppe)(2)]PF(6) (SCAR05) and cis
      [RuCl(2)(dppb)(bipy)] (SCAR06), and their free ligands are described and
      discussed. All compounds showed excellent MIC against MTB, low cytotoxicity and a
      selectivity index higher than 10. Also, all compounds showed significant
      intracellular inhibition and the compound SCAR05 showed a better activity than
      rifampin and SQ109. This is the first report of activity against in vitro
      infection of ruthenium compounds.

PMID- 21875765
TI  - Synthesis, antiproliferative activity and DNA binding study of mixed
      ammine/cyclohexylamine platinum(II) complexes with 1-(substituted benzyl)
      azetidine-3, 3-dicarboxylates.
AB  - A novel series of ammine/cyclohexylamine platinum(II) complexes with 1
      (substituted benzyl) azetidine-3, 3-dicarboxylates as leaving groups have been
      synthesized and characterized. All complexes were characterized by elemental
      analysis, IR, (1)H NMR, and ESI-MS spectra. The in vitro antiproliferative
      activities of the platinum-based compounds have been investigated against several
      human cancer cell lines, indicating that complexes 1 and 11 showed comparable
      cytotoxicity to those of cisplatin and oxaliplatin against four cell lines,
      superior to that of carboplatin. The results of drug safety evaluation (acute
      toxicity study) showed that complex 11 was much less toxic than cisplatin and
      oxaliplatin. Flow cytometry and agarose gel electrophoresis studies revealed that
      both complexes 1 and 11 induced apoptosis of tumor cells and demonstrated the
      binding affinity of complexes with pET22b plasmid DNA.

PMID- 21875764
TI  - Synthesis and biological evaluation of 1,9-disubstituted beta-carbolines as
      potent DNA intercalating and cytotoxic agents.
AB  - A series of novel 1,9-disubstituted beta-carbolines was designed, synthesized and
      evaluated as cytotoxic and DNA intercalating agents. Compounds 7b, 7c, 8b and 8c
      exhibited the most potent cytotoxic activities with IC(50) values of lower than
      20 MUM against ten human tumor cell lines. The results indicated that (1) the 3
      chlorobenzyl and 3-phenylpropyl substituents in position-9 of beta-carboline
      nucleus were the suitable pharmacophoric group giving rise to significant
      antitumor agents; (2) the length of the alkylamino side chain moiety affected
      their cytotoxic potencies, and three CH(2) units were more favorable. In
      addition, these compounds were found to exhibit remarkable DNA intercalating
      effects.

PMID- 21875766
TI  - The experiences of undergraduate Assistants in Nursing (AIN).
AB  - BACKGROUND: University academic timelines and a shortage of clinical placements
      available for students have created challenges for universities to provide
      maximum clinical exposure and preparation for practise. A State-run health system
      in Australia developed an incentive whereby students are actively recruited to
      work as Assistants in Nursing (AINs) whilst completing their undergraduate
      nursing programme, enabling them to enhance clinical skills learned during
      university. There have been no previous studies that reflect their experiences.
      AIM: This study aimed to explore and describe experiences of undergraduate AINs
      in the nursing workforce. METHOD: Semi-structured interviews were used to obtain
      in-depth accounts of the undergraduate AIN experience. Six participants who were
      employed at various healthcare facilities around the Sydney metropolitan area
      comprised the sample. Interviews were digitally recorded and transcribed
      verbatim. Data were thematically analysed. FINDINGS: Three main themes emerged
      from the data: becoming part of the team, understanding the scope of the AIN
      role, and working outside your comfort zone. CONCLUSION: Findings can add to
      international discussions in the literature related to the training and education
      of ancillary nursing staff. Furthermore findings provide insights into some of
      the challenges faced by tertiary institutions in preparing students for the
      clinical work environment. Whilst the employment of undergraduate AIN's can be an
      effective strategy, the lack of formalised guidelines to inform those working
      with undergraduate AINs may hinder the full potential of their employment.

PMID- 21875767
TI  - Marked changes in body composition following neoadjuvant chemotherapy for
      oesophagogastric cancer.
AB  - BACKGROUND & AIMS: Patients with sarcopenia [reduced fat free mass (FFM)] have a
      higher incidence of chemotherapy-related toxicity and decreased survival. As
      there are no such data in patients with oesophagogastric cancer (OGC), this study
      investigated changes in body composition in OGC patients receiving neoadjuvant
      chemotherapy (NAC). METHODS: OGC patients who had CT scans before and after NAC
      were studied. CT images at the L3 vertebral level were analysed using
      SliceOmatic((r)) software to derive estimates of FFM and fat mass (FM).
      Comparisons were made between pre- and post-NAC CT images. Data are reported as
      mean +/- SD. RESULTS: Forty-seven patients (34 male) aged 63 +/- 12 years were
      studied and 79% completed their course of NAC. The interval between CT scans was
      107 +/- 27 days. The proportion of patients with sarcopenia increased from 57%
      pre-NAC to 79% post-NAC (p = 0.046). During NAC there were significant reductions
      in estimated FFM and FM (2.9 +/- 4.7 kg, p < 0.0001 and 1.3 +/- 3.2 kg, p =
      0.007, respectively). No association was demonstrated between loss of FFM and non
      completion of NAC, increased hospital stay or mortality. CONCLUSIONS: In patients
      with OGC commencing NAC, sarcopenia was present in 57%. NAC was associated with
      further reductions in FFM and an increase in the proportion of patients becoming
      sarcopenic.

PMID- 21875768
TI  - Evaluation of environmental sensitivity of the marine regions.
AB  - The knowledge about environmental sensitivity of the marine regions to
      radionuclide release can be used for the development of response strategies and
      improvement of design-maker systems. The present results are based on the
      consequences analysis after potential Russian submarine accident involving a
      modern vessel. The radioecological consequences are based on modelling of
      potential releases of radionuclides, radionuclide transport and uptake in the
      marine environment. The sensitivity analysis is based on the comparison of the
      results of simulations with the recommendations and criterions for protection of
      the human population and the environment. The results show that the doses to
      marine organisms living in the sea sediment near the accident location, and dose
      rates to the critical group are the most sensitive state parameters (endpoints)
      for describing the consequences to the marine environment in the present
      evaluation.

PMID- 21875769
TI  - Effect of lowering dialysate sodium concentration on interdialytic weight gain
      and blood pressure in patients undergoing thrice-weekly in-center nocturnal
      hemodialysis: a quality improvement study.
AB  - BACKGROUND: Patients on in-center nocturnal hemodialysis therapy typically
      experience higher interdialytic weight gain (IDWG) than patients on conventional
      hemodialysis therapy. We determined the safety and effects of decreasing
      dialysate sodium concentration on IDWG and blood pressure in patients on thrice
      weekly in-center nocturnal hemodialysis therapy. STUDY DESIGN: Quality
      improvement, pre-post intervention. SETTINGS & PARTICIPANTS: 15 participants in a
      single facility. QUALITY IMPROVEMENT PLAN: Participants underwent three 12-week
      treatment phases, each with different dialysate sodium concentrations, as
      follows: phase A, 140 mEq/L; phase B, 136 or 134 mEq/L; and phase A(+), 140
      mEq/L. Participants were blinded to the exact timing of the intervention.
      OUTCOMES: IDWG, IDWG/dry weight (IDWG%), and blood pressure. MEASUREMENTS:
      Outcome data were obtained during the last 2 weeks of each phase and compared
      with mixed models. The fraction of sessions with adverse events (eg, cramping and
      hypotension) also was reported. RESULTS: IDWG, IDWG%, and predialysis systolic
      blood pressure decreased significantly by 0.6 +/- 0.6 kg, 0.6% +/- 0.8%, and 8.3
      +/- 14.9 mm Hg, respectively, in phase B compared with phase A (P < 0.05 for all
      comparisons). No differences in predialysis diastolic and mean arterial or
      postdialysis blood pressures were found (P > 0.05 for all comparisons). The
      proportion of treatments with intradialytic hypotension was low and similar in
      each phase (P = 0.9). In phase B compared with phase A, predialysis plasma sodium
      concentration was unchanged (P > 0.05), whereas postdialysis plasma sodium
      concentration decreased by 3.7 +/- 1.9 mEq/L (P < 0.05). LIMITATIONS: Modest
      sample size. CONCLUSION: Decreasing dialysate sodium concentrations in patients
      undergoing thrice-weekly in-center nocturnal hemodialysis resulted in a clinical
      and statistically significant decrease in IDWG, IDWG%, postdialysis plasma sodium
      concentration, and predialysis systolic blood pressure without increasing adverse
      events. Prolonged exposure to higher than required dialysate sodium
      concentrations may drive IDWG and counteract some of the purported benefits of
      "go-slow" (longer session length) hemodialysis.

PMID- 21875770
TI  - The expression and function of miRNA-451 in non-small cell lung cancer.
AB  - miRNAs are small, non-coding RNAs that negatively regulate gene expression at the
      post-transcriptional and translational levels. miRNA-451 was previously reported
      to be down-regulated in gastric and colorectal cancers. Here, we showed that
      miRNA-451 expression decreased in non-small cell lung cancer (NSCLC) tissues and
      that its expression was negatively associated with lymph node metastasis, the
      stage of TNM classification and poor prognosis of NSCLC patients. Moreover,
      significantly different miRNA-451 expression levels were found between smoking
      and non-smoking patients. The overexpression of miRNA-451 inhibited cell cycle
      progression, cellular migration and the invasive ability of NSCLC cells.
      Increased miRNA-451 expression also promoted anoikis of NSCLC cells. Together,
      these data suggested that aberrantly expressed miRNA-451 may be associated with
      the development of NSCLC.

PMID- 21875771
TI  - Variability in placebo analgesia and the role of fear of pain--an ERP study.
AB  - Fear of pain (FOP) and its effect on placebo analgesia was investigated. It was
      hypothesized that FOP should interfere with placebo-mediated pain inhibition and
      result in weaker placebo responding in pain intensity, pain unpleasantness,
      stress, and event-related potentials to contact heat pain. Thirty-three subjects
      participated in a balanced 2 condition (natural history, placebo)*3 test
      (pretest, posttest 1, posttest 2) within-subject design, tested on 2 separate
      days. FOP was measured by the Fear of Pain Questionnaire and subjective stress by
      the Short Adjective Check List. Placebo effects were found on reported pain
      unpleasantness and N2 and P2 amplitudes. FOP was related to reduced placebo
      responding in pain unpleasantness, but this was only evident for the subjects who
      received the placebo condition on day 1. Subjects who received the placebo
      condition on day 1 experienced more pretest stress than those who received the
      placebo condition on day 2 (ie, reversed condition order), and this explained the
      interaction effect on placebo responding. FOP was related to reduced placebo
      responding on P2 amplitude, whereas placebo responding on N2 amplitude was
      unaffected by FOP. Higher placebo responses on N2 and P2 amplitudes were both
      related to higher placebo analgesic magnitude in pain unpleasantness. In
      conclusion, increased FOP was found to reduce subjective and electrophysiological
      placebo analgesic responses.

PMID- 21875772
TI  - Methamphetamine: here we go again?
AB  - Following more than two decades of generally increasing trends in the use and
      abuse of methamphetamine in certain parts of the country, prevalence indicators
      for the drug began to decrease in the mid-2000's-but was this decrease signaling
      the end of the "meth problem"? This paper has compiled historical and recent data
      from supply and demand indicators to provide a broader context within which to
      consider the changes in trends over the past half decade. Data suggest supply
      side accommodation to changes in precursor chemical restrictions, with prevalence
      indicators beginning to attenuate in the mid-2000's and then increasing again by
      2009-2010. Results support the need for continuing attention to control and
      interdiction efforts appropriate to the changing supply context and to continuing
      prevention efforts and increased number of treatment programs.

PMID- 21875773
TI  - Diagnostic accuracy of blood and CSF lactate in identifying children with
      mitochondrial diseases affecting the central nervous system.
AB  - OBJECTIVE: To determine the diagnostic accuracy of blood and cerebrospinal fluid
      (CSF) lactate and pyruvate concentrations in identifying children with
      mitochondrial diseases (MD) affecting the central nervous system (CNS). METHODS:
      We studied lactate and pyruvate concentrations in paired samples of blood and CSF
      collected concurrently from 17 patients with MD (Leigh encephalomyelopathy 10,
      MELAS 5, Pearson disease 1, PDH deficiency 1) and those from control patients
      (n=49). RESULTS: Although blood and CSF variables (lactate, pyruvate
      concentrations and lactate/pyruvate ratio) were significantly higher in the
      mitochondrial group than in the control group, there was considerable overlap of
      individual values between these two groups. The maximum value of the area under
      the receiver operating characteristic curve (AUC) was observed for the CSF
      lactate concentration (0.994, optimal cut-off value 19.9 mg/dl, sensitivity 0.941
      and specificity 1.00), followed by the CSF pyruvate level (0.983). There was an
      inverse relationship between blood lactate and lactate CSF/blood ratio. For blood
      lactate concentrations between 20 and 40 mg/dl, a significant difference was also
      noted in the lactate CSF/blood ratio between the two groups (AUC 1.0, optimal cut
      off value 0.91, sensitivity 1.0 and specificity 1.0). CONCLUSIONS: Our study
      suggests that that CSF lactate level>19.9 mg/dl is the most reliable variable for
      identifying patients with MD affecting the CNS. When blood lactate concentrations
      are marginally elevated (20-40 mg/dl), lactate CSF/blood ratio>0.91 may also
      provide diagnostic information.

PMID- 21875774
TI  - Stress-only Tc-99m myocardial perfusion imaging in an emergency department chest
      pain unit.
AB  - BACKGROUND: Stress-only myocardial perfusion imaging (MPI) saves time by
      eliminating rest imaging, which is important for emergency department (ED)
      throughput but has not been studied in an ED population. STUDY OBJECTIVE: To
      determine the prognosis of a normal stress-only MPI study compared to a normal
      rest-stress MPI and establish its effectiveness in an ED setting. METHODS: All
      patients evaluated in the ED over 6.5 years who underwent a stress-only
      technetium-99m gated MPI were compared to those who had a rest-stress study. All
      cause mortality was determined using the Social Security Death Index. Survival
      was analyzed in patients with normal and abnormal MPI results. RESULTS: A total
      of 4145 studies (2340 stress-only, 1805 rest-stress) were performed. Patients'
      average age was 57.9 years, 38.5% were male, and most had an intermediate or low
      pretest risk of coronary artery disease (87.7%). Average follow-up was 35.9 +/-
      20.9 months. In patients with normal perfusion, at 1 year of follow-up there were
      11 deaths in the stress-only group (0.5% 1-year mortality), and 13 deaths in the
      rest-stress cohort (1.1% 1-year mortality). At the end of follow-up, the stress
      only group had a lower all-cause mortality (p < 0.0001) and similar risk adjusted
      all-cause mortality (p = 0.10) than the rest-stress cohort. Patients with
      abnormal perfusion demonstrated the expected differential prognosis based on
      total perfusion deficits in both groups. CONCLUSIONS: A normal stress-only MPI
      study has a benign 1-year prognosis similar to a rest-stress study when performed
      in the ED. The ability to triage patients more rapidly and reduce radiation
      exposure represents an attractive alternative for low-risk patients.

PMID- 21875775
TI  - Development of a university-based emergency department network: lessons learned.
AB  - BACKGROUND: As part of the growth of emergency medical care in our state, our
      university-based emergency medicine practice developed a network of affiliated
      emergency department (ED) practices. The original practices were academic and
      based on a faculty practice model; more recent network development incorporated a
      community practice model less focused on academics. OBJECTIVE: This article
      discusses the growth of that network, with a focus on the recent addition of a
      county-wide two-hospital emergency medicine practice. During the transition of
      the two EDs from a contract management group to the university network, six
      critical areas in need of restructuring were identified: 1) departmental
      leadership, 2) recruitment and retention of clinical staff members, 3) staffing
      strategies, 4) relationships with key constituents, 5) clinical operations,
      supplies, and equipment, and 6) compensation structure. The impact of changes was
      measured by comparison of core measures, efficiency metrics, patient volumes,
      admissions, and transfers to the academic medical center before and after the
      implementation of our practice model. CONCLUSION: Our review and modification of
      these components significantly improved the quality and efficiency of care at the
      community hospital system. The consistent presence of board certified emergency
      physicians optimized utilization of clinical resources in the community hospital
      and the academic health system. This dynamic led to a mutually beneficial merger
      of these major state healthcare systems.

PMID- 21875776
TI  - Substituting whole blood for urine in a bedside pregnancy test.
AB  - BACKGROUND: Point-of-care testing for rapid detection of pregnancy in women of
      reproductive age is common practice in the emergency department. Commercially
      available rapid human chorionic gonadotropin (hCG) immunoassays are validated for
      use with urine and serum, but not whole blood. STUDY OBJECTIVES: We assessed the
      validity of using whole blood to detect pregnancy using a point-of-care hCG assay
      by comparing it to a laboratory quantitative serum hCG assay as the criterion
      standard. METHODS: A convenience sample of female patients of reproductive age
      (18-51 years) submitted 5mL of whole blood, from which two drops were immediately
      applied to a point-of-care hCG kit, with results recorded at 10min. The remainder
      of each whole blood specimen was sent to the hospital laboratory for the
      criterion-standard quantitative serum hCG assay. The criterion standard for a
      positive pregnancy test was defined as quantitative serum hCG>=5 mIU/mL.
      Investigators performing the whole blood test and laboratory technicians
      performing the quantitative serum assay were blinded to one another's results.
      RESULTS: There were 633 patients enrolled, with a mean age of 30 years (+/- 7.7
      years); 34% of the patients were pregnant. Overall, the whole blood pregnancy
      test was 95.8% sensitive (negative predictive value 97.9%), whereas the urine
      test was 95.3% sensitive (negative predictive value 97.6%); the specificity and
      positive predictive value of both tests was 100%. CONCLUSION: Using a standard
      point-of-care qualitative hCG immunoassay kit, whole blood may be used for rapid
      detection of pregnancy with similar, or greater, accuracy than urine.

PMID- 21875777
TI  - Early and long-term outcomes after percutaneous coronary intervention of
      unprotected left main coronary disease with drug-eluting stents in patients with
      non-ST-elevation acute coronary syndrome.
AB  - BACKGROUND: Patients presenting with non-ST-elevation acute coronary syndrome
      (NSTE-ACS) and unprotected left main coronary disease (ULMCD) are among the
      highest risk patients but current consensus guidelines do not address the optimal
      timing and mode of revascularization for these individuals. METHODS: In this
      single-centre registry, we evaluated the clinical outcomes of 151 consecutive
      patients with NSTE-ACS and ULMCD who underwent percutaneous coronary intervention
      with drug-eluting stents from 2005 to 2009. RESULTS: Overall in-hospital major
      adverse cardiac event (MACE) rate was 5.3%, mortality rate was 0.7%. At 30
      months+/-15 months, 30 patients (19.9%) experienced MACE. The 4-year cumulative
      survival rate of no MACE was 73.2% and cumulative survival rate was 90.6%. Left
      ventricular ejection fraction (hazard ratio [HR] 0.947; 95% confidence interval
      [CI], 0.898-0.998; P=0.043) and SYNTAX [SYNergy between percutaneous coronary
      intervention with TAXus and cardiac surgery] score>=33 (HR 1.28; 95% CI, 1.025
      1.433; P=0.029) were associated with MACE, while only left ventricular ejection
      fraction (HR 0.82; 95% CI, 0.69-0.973; P=0.023) was associated with mortality.
      CONCLUSIONS: Our study demonstrates the feasibility of percutaneous coronary
      intervention with drug-eluting stents in patients with NSTE-ACS and ULMCD. The
      early and long-term outcomes were acceptable. Left ventricular ejection fraction
      and SYNTAX score>=33 predict MACE and only left ventricular ejection fraction
      predicts mortality.

PMID- 21875778
TI  - Use of clopidogrel post-coronary artery bypass surgery in canadian patients with
      acute coronary syndromes.
AB  - BACKGROUND: Randomized trials have established the efficacy of clopidogrel in
      acute coronary syndromes (ACS). The benefit of clopidogrel has also been observed
      in the subgroup of ACS patients who subsequently undergo coronary artery bypass
      surgery (CABG); however, this therapy is discontinued preoperatively and the
      frequency with which clopidogrel is restarted post-CABG is unknown. METHODS: We
      examined the pattern of clopidogrel use in the Canadian Global Registry of Acute
      Coronary Events (GRACE), GRACE2, and CANRACE (2003-2008) post-CABG ACS patients.
      We stratified the patients according to whether they underwent CABG during their
      index hospitalization for ACS and whether they were prescribed clopidogrel at
      discharge. RESULTS: Among those patients in whom clopidogrel status at discharge
      was known, 5904 (60%) of 9841 were discharged from hospital on clopidogrel. Use
      of clopidogrel at discharge was observed in 2222 (40.8%) of 5443 patients who
      were medically managed (ie, did not undergo percutaneous coronary intervention
      [PCI] or CABG) and in 3585 (90.1%) of 3980 patients who underwent in-hospital
      PCI. Overall, 455 (3.3%) of 13,776 patients underwent CABG during the index
      hospitalization; 255 (56%) patients were started on clopidogrel during the first
      24 hours, and 66 of these patients (25.9%) were discharged on clopidogrel. In
      contrast, 5681 (61.3%) of the 9262 patients who did not undergo in-hospital CABG
      were discharged on clopidogrel. CONCLUSIONS: Although current guidelines
      recommend the use of clopidogrel post-CABG in patients with ACS, our observations
      suggest that only 1 in 4 or 5 Canadian patients are discharged on this therapy.

PMID- 21875779
TI  - KCNJ2 variant of unknown significance reclassified as long QT syndrome causing
      ventricular fibrillation.
AB  - KCNJ2 is the only gene implicated in Andersen-Tawil syndrome. Sudden cardiac
      arrest is rare in Andersen-Tawil syndrome. However, sudden cardiac arrest is
      often the index presentation in other forms of long QT syndrome. We present an
      unreported variant in the KCNJ2 gene, associated with long QT syndrome, that
      presented with ventricular fibrillation. Exercise testing and adrenaline infusion
      were useful in assigning pathogenicity to this variant of unknown significance.

PMID- 21875780
TI  - The insula-claustrum region and delusions in schizophrenia.
AB  - OBJECTIVE: We examined the relationship between cerebral gray matter (GM) volume
      and severity of delusions and hallucinations in adults with schizophrenia.
      METHOD: MRI scans in 43 patients with schizophrenia were acquired. Correlations
      were computed between GM volume and clinician ratings of hallucinations and
      delusions. RESULTS: The analysis revealed significant inverse correlations
      between ratings of the severity of delusions and volumes of the left claustrum
      and right insula. Significant correlations were not observed between cerebral GM
      volume and ratings of hallucinations. CONCLUSION: The insula/claustrum region may
      be critical to the experience of delusions and more careful scrutiny of the
      claustrum in relation to schizophrenia appears warranted.

PMID- 21875782
TI  - American College of Radiology Appropriateness Criteria((r))--locally advanced
      (high-risk) prostate cancer.
AB  - The American College of Radiology Appropriateness Criteria are evidence-based
      guidelines for specific clinical conditions that are reviewed every 2 years by a
      multidisciplinary expert panel. The guideline development and review include an
      extensive analysis of current medical literature from peer-reviewed journals and
      the application of a well-established consensus methodology (modified Delphi) to
      rate the appropriateness of imaging and treatment procedures by the panel. In
      those instances where evidence is lacking or not definitive, expert opinion may
      be used to recommend imaging or treatment. This review focuses on locally
      advanced prostate cancer and the evidence for treatment outcomes, both toxicity
      and efficacy, across the three major treatment modalities of external beam
      radiotherapy, brachytherapy and surgery. Only data that could pass contemporary
      quality metrics were used to form this report. This body of literature suffers
      from an absence of trials prospectively comparing therapies for efficacy and a
      lack of long-term prospective comparisons of toxicity. Upon review of these data,
      the authors concluded that there are several acceptable methods for the treatment
      of locally advanced prostate cancer that is highly dependent of the patient's
      clinical (both prostate cancer-specific and comorbidity-specific) parameters at
      diagnosis.

PMID- 21875781
TI  - Striatal volumes in pediatric bipolar patients with and without comorbid ADHD.
AB  - The most prevalent comorbid disorder in pediatric bipolar disorder (BD) is
      attention-deficit/hyperactivity disorder (ADHD). As caudate volume abnormalities
      have been demonstrated in both BD and ADHD, this study sought to determine
      whether these findings could be attributed to separable effects from either
      diagnosis. High resolution anatomical magnetic resonance (MRI) images were
      obtained from youth in 4 groups: BD with comorbid ADHD (n=17), BD without
      comorbid ADHD (n=12), youth with ADHD alone (n=11), and healthy control subjects
      (n=24). Caudate, putamen, and globus pallidus volumes were manually traced for
      each subject using BrainImageJava software by a reliable rater blinded to
      diagnosis. There was a significant effect of diagnosis on striatal volumes, with
      ADHD associated with decreased caudate and putamen volumes, and BD associated
      with increased caudate, putamen, and globus pallidus volumes. Thus, the presence
      or absence of comorbid ADHD in patients with BD was associated with distinct
      alterations in caudate volumes, suggesting that these groups have different, but
      related, mechanisms of neuropathology.

PMID- 21875783
TI  - Comparative effectiveness of radial probe endobronchial ultrasound versus CT
      guided needle biopsy for evaluation of peripheral pulmonary lesions: a randomized
      pragmatic trial.
AB  - In many patients the optimal method of investigation of peripheral pulmonary
      lesions (PPL) is not clear. We performed a prospective randomized pragmatic trial
      to determine the comparative effectiveness of endobronchial ultrasound-guided
      transbronchial lung biopsy (EBUS-TBLB) and CT-guided percutaneous needle biopsy
      (CT-PNB) for the investigation of PPL. Overall complication rates were higher in
      those undergoing CT-PNB (27% v 3%, p = 0.03), while diagnostic accuracy of EBUS
      TBLB was shown to be non-inferior to that of CT-PNB. Expected diagnostic accuracy
      and complication rates are likely to differ for individual patients on the basis
      of specific complex clinicoradiologic factors, which will influence the cost
      benefit analysis between EBUS-TBLB and CT-PNB for individual patients. Further
      studies are required to examine the effect of these factors on clinical decision
      making.

PMID- 21875785
TI  - Measuring pacemaker dose: a clinical perspective.
AB  - Recently in our clinic, we have seen an increased number of patients presenting
      with pacemakers and defibrillators. Precautions are taken to develop a treatment
      plan that minimizes the dose to the pacemaker because of the adverse effects of
      radiation on the electronics. Here we analyze different dosimeters to determine
      which is the most accurate in measuring pacemaker or defibrillator dose while at
      the same time not requiring a significant investment in time to maintain an
      efficient workflow in the clinic. The dosimeters analyzed here were ion chambers,
      diodes, metal-oxide-semiconductor field effect transistor (MOSFETs), and
      optically stimulated luminescence (OSL) dosimeters. A simple phantom was used to
      quantify the angular and energy dependence of each dosimeter. Next, 8 patients
      plans were delivered to a Rando phantom with all the dosimeters located where the
      pacemaker would be, and the measurements were compared with the predicted dose. A
      cone beam computed tomography (CBCT) image was obtained to determine the
      dosimeter response in the kilovoltage energy range. In terms of the angular and
      energy dependence of the dosimeters, the ion chamber and diode were the most
      stable. For the clinical cases, all the dosimeters match relatively well with the
      predicted dose, although the ideal dosimeter to use is case dependent. The
      dosimeters, especially the MOSFETS, tend to be less accurate for the plans, with
      many lateral beams. Because of their efficiency, we recommend using a MOSFET or a
      diode to measure the dose. If a discrepancy is observed between the measured and
      expected dose (especially when the pacemaker to field edge is <10 cm), we
      recommend analyzing the treatment plan to see whether there are many lateral
      beams. Follow-up with another dosimeter rather than repeating multiple times with
      the same type of dosimeter. All dosimeters should be placed after the CBCT has
      been acquired.

PMID- 21875784
TI  - Electrochemical sensor based on molecularly imprinted membranes at platinum
      nanoparticles-modified electrode for determination of 17beta-estradiol.
AB  - In this paper, an electrochemical sensor for 17beta-estradiol (E2) based on the
      molecular imprinting polymer (MIP) membranes had been constructed. 6
      mercaptonicotinic acid (MNA) and E2 were first assembled on the surface of
      platinum nanoparticles-modified glassy carbon electrode (PtNPs/GCE) by the
      formation of Pt-S bonds and hydrogen-bonding interactions, and subsequently the
      polymer membranes were formed by electropolymerization. Finally, a novel
      molecularly imprinted sensor (MIS) was obtained after removal of E2. Experimental
      parameters such as deposition time, scan cycles, pH value and accumulation
      condition were optimized. Under optimal conditions, the MIS exhibited a large
      adsorption capacity and high selectivity. A good linearity was obtained in the
      range of 3.0*10(-8)-5.0*10(-5)molL(-1) (r=0.996) with an estimated detection
      limit of 1.6*10(-8)molL(-1). MIS had been successfully used to analyze E2 in
      water samples without complex pretreatment. Meanwhile, the average recoveries
      were higher than 93.9% with RSD<3.7%. All results above reveal that MIS is an
      effective electrochemical technique to determine E2 real-time in complicated
      matrix.

PMID- 21875786
TI  - Single cell oil production from rice hulls hydrolysate.
AB  - Rice hull hydrolysate was used as feedstock for microbial lipids production using
      the oleaginous fungus Mortierella isabellina. Kinetic experiments were conducted
      in C/N ratios 35, 44 and 57 and the oil accumulation into fungal biomass was 36%,
      51.2% and 64.3%, respectively. A detailed mathematical model was used in order to
      describe the lipid accumulation process. This model was able to predict reducing
      sugar and nitrogen consumption, fat-free biomass synthesis and lipid
      accumulation. Neutral lipids constitute the predominant lipid fraction, while the
      major fatty acids were oleic, palmitic and linoleic acid. Fatty acids of long
      aliphatic chain were not detected, thus the microbial oil produced is a promising
      feedstock for biodiesel production.

PMID- 21875787
TI  - Technoeconomic analysis of five microalgae-to-biofuels processes of varying
      complexity.
AB  - The economics surrounding five algae-to-fuels process scenarios were examined.
      The different processes modeled were as follows: an open pond producing either
      triacylglycerides (TAG) or free fatty acid methyl ester (FAME), a solar-lit
      photobioreactor producing either FAME or free fatty acids (FFA), and a light
      emitting diode irradiated (LED-lighted) photobioreactor producing TAG. These
      processes were chosen to represent both classical and esoteric approaches
      presented in the open literature. Viable (or suggested) processing techniques to
      liberate and purify (and convert) the microalgal triacylglycerides were then
      modeled to accompany each growth option. The investment and cost per kg of fuel
      or fuel precursor for each process was determined. The open pond produced TAG at
      ~$7.50/kg, while the process using the LED-lit photobioreactor produced TAG at
      ~$33/kg. The scenario containing the solar-lit photobioreactor produced FAME at
      ~$25/kg, while the open pond produced FAME at ~$4/kg. The scenario containing the
      solar-lit photobioreactor produced FFA at ~$29/kg. The open pond scenarios appear
      to be closest to the $1/kg pricepoint at this time, and thus are the most viable
      economic options. Future technological advancements that reduce the cost of
      bioreactor vessels, LED lighting, and solvent recovery, may reduce the oil
      production costs of these scenarios to a more attractive level.

PMID- 21875788
TI  - Selective reduction of the pathogenic load of cow manure in an industrial-scale
      continuous-feeding vermireactor.
AB  - Vermicomposting is a suitable technology for processing different wastes, to
      produce a valuable end product (vermicompost). However, the pathogenic load of
      the waste must be greatly reduced in order to prevent risks to human health.
      Although Eisenia andrei may reduce the levels of several pathogens, the
      feasibility of vermicomposting, with regard to pathogen reduction, has not been
      tested on an industrial scale. This work studied whether vermicomposting in a
      continuous feeding vermireactor, is able to reduce the pathogenic load of cow
      manure. The effect of E. andrei on pathogens depended on the type of pathogen;
      thus, levels of Clostridium, total coliforms and Enterobacteria were not
      modified, but levels of faecal enterococci, faecal coliforms and Escherichia coli
      were reduced to acceptable levels. Pathogens could have maintained their levels
      in continuous feeding vermireactors, as fresh layers of manure are added to the
      top, which allows the vertical spread of pathogens through leaching.

PMID- 21875789
TI  - Preparation and characterization of activated carbon from sunflower seed oil
      residue via microwave assisted K2CO3 activation.
AB  - Sunflower seed oil residue, a by-product of sunflower seed oil refining, was
      utilized as a feedstock for preparation of activated carbon (SSHAC) via microwave
      induced K(2)CO(3) chemical activation. SSHAC was characterized by Fourier
      transform infrared spectroscopy, nitrogen adsorption-desorption and elemental
      analysis. Surface acidity/basicity was examined with acid-base titration, while
      the adsorptive properties of SSHAC were quantified using methylene blue (MB) and
      acid blue 15 (AB). The monolayer adsorption capacities of MB and AB were 473.44
      and 430.37 mg/g, while the Brunauer-Emmett-Teller surface area, Langmuir surface
      area and total pore volume were 1411.55 m(2)/g, 2137.72 m(2)/g and 0.836 cm(3)/g,
      respectively. The findings revealed the potential to prepare high surface area
      activated carbon from sunflower seed oil residue by microwave irradiation.

PMID- 21875790
TI  - Novel organic solvent-responsive expression vectors for biocatalysis: application
      for development of an organic solvent-tolerant biodesulfurizing strain.
AB  - Biodesulfurization is an attractive alternative to hydrodesulfurization for
      lowering the sulfur content of petroleum products. However, the fuel oils are
      toxic to microorganisms, which have seriously hindered the application of
      biodesulfurization. Here, a solvent-tolerant desulfurizing bacterium, Pseudomonas
      putida DS23, was developed using one of the organic solvent-responsive expression
      vectors newly constructed for biocatalysis, in which gene expression could be
      regulated in an organic solvent-dependent fashion. The biodesulfurizing activity
      of P. putida DS23 could be induced by all the organic solvents used. P. putida
      DS23 cells induced by n-hexane were able to degrade 56% of 0.5 mM DBT in 12 h in
      the biphasic reaction containing 33.3% (v/v) n-hexane, while the strain induced
      by isopropyl beta-D-1-thiogalactopyranoside could only degrade 26% of 0.5 mM DBT.
      These results suggested that use of the constructed organic solvent-responsive
      expression vectors can facilitate the biphasic biocatalysis involving organic
      solvents.

PMID- 21875791
TI  - Metabolic adaptation of Pteris vittata L. gametophyte to arsenic induced
      oxidative stress.
AB  - The sporophyte and gametophyte of Pteris vittata are arsenic hyperaccumulators,
      however, little is known about the mechanism by which the gametophyte deals with
      this toxic element. An in vitro system (spores grown in arsenic amended nutrient
      media) was used to investigate the impact of arsenic on growth of the gametophyte
      and the role of antioxidative systems in combating As-stress. When mature spores
      of P. vittata were grown in medium amended with 0-50 mg kg(-1) of arsenic (as
      arsenate), the arsenic concentration in the gametophyte increased, with
      increasing arsenate in the media, but did not inhibit the spore germination and
      biomass development. Increases in the level of antioxidant enzymes, superoxide
      dismutase, catalase, ascorbate peroxidase, glutathione reductase, and glutathione
      Stransferase) and of ascorbic acid and glutathione probably enabled the
      gametophyte to withstand the oxidative stress caused by arsenate.

PMID- 21875792
TI  - Optimizing the electrode size and arrangement in a microbial electrolysis cell.
AB  - This study investigates the influence of anode and cathode size and arrangement
      on hydrogen production in a membrane-less flat-plate microbial electrolysis cell
      (MEC). Protein measurements were used to evaluate microbial density in the carbon
      felt anode. The protein concentration was observed to significantly decrease with
      the increase in distance from the anode-cathode interface. Cathode placement on
      both sides of the carbon felt anode was found to increase the current, but also
      led to increased losses of hydrogen to hydrogenotrophic activity leading to
      methane production. Overall, the best performance was obtained in the flat-plate
      MEC with a two-layer 10 mm thick carbon felt anode and a single gas-diffusion
      cathode sandwiched between the anode and the hydrogen collection compartments.

PMID- 21875794
TI  - Thermodynamic prediction of hydrogen production from mixed-acid fermentations.
AB  - The MixAlcoTM process biologically converts biomass to carboxylate salts that may
      be chemically converted to a wide variety of chemicals and fuels. The process
      utilizes lignocellulosic biomass as feedstock (e.g., municipal solid waste,
      sewage sludge, and agricultural residues), creating an economic basis for
      sustainable biofuels. This study provides a thermodynamic analysis of hydrogen
      yield from mixed-acid fermentations from two feedstocks: paper and bagasse.
      During batch fermentations, hydrogen production, acid production, and sugar
      digestion were analyzed to determine the energy selectivity of each system. To
      predict hydrogen production during continuous operation, this energy selectivity
      was then applied to countercurrent fermentations of the same systems. The
      analysis successfully predicted hydrogen production from the paper fermentation
      to within 11% and the bagasse fermentation to within 21% of the actual
      production. The analysis was able to faithfully represent hydrogen production and
      represents a step forward in understanding and predicting hydrogen production
      from mixed-acid fermentations.

PMID- 21875793
TI  - Impact of indigenous microorganisms on Escherichia coli O157:H7 growth in cured
      compost.
AB  - Both autoclaving and dry-heat treatments were applied to dairy manure-based
      compost to achieve target populations of indigenous microorganisms. A 3 strain
      mixture of Escherichia coli O157:H7 of ca. 2 log CFU/g was inoculated into
      acclimated autoclaved compost (AAC) and dry heat-treated compost (DHTC) with
      different moistures, and stored at 8, 22, or 30  degrees C. Only selected groups
      of microorganisms grew in AAC during acclimation, whereas the relative ratio of
      each group of microorganisms was maintained in DHTC after heat treatment. E. coli
      O157:H7 grew more in AAC than DHTC in the presence of same level of indigenous
      mesophiles. However, control compost (no heat treatment) did not support E. coli
      O157:H7 growth. Our results revealed that both the type and population of
      indigenous microorganisms is critical for suppressing E. coli O157:H7 growth in
      compost, and dry-heat treatment can result in a compost product which resembles
      cured compost with different levels of indigenous microorganisms.

PMID- 21875795
TI  - Co-pyrolysis of walnut shell and tar sand in a fixed-bed reactor.
AB  - This study investigated potential synergistic activities between tar sand and
      walnut shell during co-pyrolysis. A series of pyrolysis studies were conducted
      under specific operating conditions in a fixed-bed reactor. The highest yield of
      bio-oil from the co-pyrolysis was 31.84 wt.%, which represented an increase of
      7.88 wt.% compared to the bio-oil yield from the pyrolysis of walnut shell alone.
      The bio-oils were characterized using various spectroscopic and chromatographic
      analysis techniques. The results indicated that the synergetic effect increased
      the co-pyrolysis bio-oil yield and its quality. Consequently, the results
      indicate that the bio-oils obtained will be suitable for the production of fuels
      and chemicals as feedstock after required improvements.

PMID- 21875796
TI  - 2,5-Disubstituted-1,3,4-oxadiazoles/thiadiazole as surface recognition moiety:
      design and synthesis of novel hydroxamic acid based histone deacetylase
      inhibitors.
AB  - The enzymatic inhibition of histone deacetylase activity has come out as a novel
      and effectual means for the treatment of cancer. Two novel series of 2-[5-(4
      substitutedphenyl)-[1,3,4]-oxadiazol/thiadiazol-2-ylamino]-pyrimidine-5
      carboxylic acid (tetrahydro-pyran-2-yloxy)-amides were designed and synthesized
      as novel hydroxamic acid based histone deacetylase inhibitors. The
      antiproliferative activities of the compounds were investigated in vitro using
      histone deacetylase inhibitory assay and MTT assay. The synthesized compounds
      were also tested for antitumor activity against Ehrlich ascites carcinoma cells
      in Swiss albino mice. The efforts were also made to establish structure-activity
      relationships among synthesized compounds. The results of the present studying
      indicates 2,5-disubstituted 1,3,4-oxadiazole/thiadiazole as promising surface
      recognition moiety for development of newer hydroxamic acid based histone
      deacetylase inhibitor.

PMID- 21875797
TI  - Synthesis of a quinazoline derivative: a new alpha1-adrenoceptor ligand for
      conjugation to quantum dots to study alpha1-adrenoceptors in living cells.
AB  - Quantum dots (QDs) that are conjugated to small molecule derivatives of drugs and
      endogenous ligands may be useful tools to study the distribution and dynamic of
      membrane bound receptors, ion channels and transporters in live cells. In order
      to use these tools, it is necessary to functionalize QDs with bioactive ligands.
      In this paper, we successfully synthesized a ligand of alpha(1)-adrenoceptor that
      could be conjugated to QDs. In addition, the conjugation of the ligands to QDs
      and their biological activity were evaluated through binding assay with 30 nM QD
      conjugates in living human embryonic kidney 293 cells.

PMID- 21875798
TI  - Towards rational design of cannabinoid receptor 1 (CB1) antagonists for
      peripheral selectivity.
AB  - CB1 receptor antagonists that are peripherally restricted were targeted.
      Compounds with permanent charge as well as compounds that have increased polar
      surface area were made and tested against CB1 for binding and activity.
      Sulfonamide and sulfamide with high polar surface area and good activity at CB1
      were rationally designed and pharmacologically tested. Further optimization of
      these compounds and testing could lead to the development of a new class of
      therapeutics to treat disorders where the CB1 receptor system has been
      implicated.

PMID- 21875799
TI  - Cellular uptake of Aib-containing amphipathic helix peptide.
AB  - Cell-penetrating peptides (CPPs) are useful tools for the delivery of hydrophilic
      bioactive molecules, such as peptides, proteins, and oligonucleotides, across the
      cell membrane. To realize the delivery of therapeutic macromolecules by CPPs, the
      CPPs are required to show resistance to protease and no cytotoxicity. In order to
      produce potent non-toxic and protease-resistant CPPs with high cellular uptake,
      we designed an amphipathic helix peptide using alpha-aminoisobutyric acid (Aib,
      U) and named it MAP(Aib). In the MAP(Aib) molecule, five Aib residues are aligned
      on the hydrophobic face of the helix and five lysine (K) residues are aligned on
      the hydrophilic face. MAP(Aib) showed potent resistance to trypsin and pronase
      compared with MAP, an amphipathic helix peptide formed by usual amino acids.
      Fluorescein-labeled MAP(Aib) efficiently traversed the A549 cell membrane,
      diffusing into the cytoplasm and slightly into the nucleus without exerting any
      cytotoxicity. In contrast, MAP was poorly taken up by the cell. These results
      indicate that the incorporation of Aib residues into CPPs markedly improves
      cellular uptake and MAP(Aib) may be a useful tool for the delivery of hydrophilic
      macromolecules.

PMID- 21875800
TI  - Design and synthesis of C35-fluorinated solamins and their growth inhibitory
      activities against human cancer cell lines.
AB  - The convergent synthesis of C35-fluorinated analogues of solamin, a mono-THF
      Annonaceous acetogenin, has been achieved by the Sonogashira coupling of the THF
      ring fragment and the fluorinated gamma-lactone fragment. It was revealed that
      the number of fluorine atoms on the gamma-lactone moiety affects the growth
      inhibitory activities against human cancer cell lines.

PMID- 21875801
TI  - MDM2-p53 protein-protein interaction inhibitors: a-ring substituted
      isoindolinones.
AB  - Structure-activity relationships for the MDM2-p53 inhibitory activity of a series
      of A-ring substituted 2-N-benzyl-3-(4-chlorophenyl)-3-(1
      (hydroxymethyl)cyclopropyl)methoxy)isoindolinones have been investigated, giving
      rise to compounds with improved potency over their unsubstituted counterparts.
      Isoindolinone A-ring substitution with a 4-chloro group for the 4-nitrobenzyl, 4
      bromobenzyl and 4-cyanobenzyl derivatives (10a-c) and substitution with a 6-tert
      butyl group for the 4-nitrobenzyl derivative (10j) were found to confer
      additional potency. Resolution of the enantiomers of 10a showed that potent MDM2
      p53 activity resided in the (-)-enantiomer ((-)-10a; IC(50)=44 +/- 6 nM). The
      cellular activity of key compounds has been examined in cell lines with defined
      p53 and MDM2 status. Compounds 10a and (-)-10a increase p53 protein levels,
      activate p53-dependent MDM2 and p21 transcription in MDM2 amplified cells, and
      show improved selectivity for growth inhibition in wild type p53 cell lines over
      the parent compound.

PMID- 21875803
TI  - Synthesis of a series of gamma-amino alcohols comprising an N-methyl isoindoline
      moiety and their evaluation as NMDA receptor antagonists.
AB  - We report a series of new stereoisomeric gamma-amino alcohols comprising an N
      methyl isoindoline moiety as ligands for the ifenprodil binding site of the NMDA
      receptor. Among the four series of stereoisomers, 8a-c, 9a-c, 10a-c, and 11a-c,
      synthesised, the highest potencies and NMDA-NR2B subtype selectivity was found
      for the methyl derivative 11a and the chloro derivative 11c, both possessing the
      [1S,1'S] configuration. However, additional moderate potency of 11a and 11c at
      the hERG channel with values of 2.6 +/- 2.4% and 1.6 +/- 2.0%, respectively,
      rendered them unsuitable for medical use.

PMID- 21875802
TI  - Lead generation of heat shock protein 90 inhibitors by a combination of fragment
      based approach, virtual screening, and structure-based drug design.
AB  - Heat shock protein 90 (Hsp90) is a molecular chaperone which regulates maturation
      and stabilization of its substrate proteins, known as client proteins. Many
      client proteins of Hsp90 are involved in tumor progression and survival and
      therefore Hsp90 can be a good target for developing anticancer drugs. With the
      aim of efficiently identifying a new class of orally available inhibitors of the
      ATP binding site of this protein, we conducted fragment screening and virtual
      screening in parallel against Hsp90. This approach quickly identified 2
      aminotriazine and 2-aminopyrimidine derivatives as specific ligands to Hsp90 with
      high ligand efficiency. In silico evaluation of the 3D X-ray Hsp90 complex
      structures of the identified hits allowed us to promptly design CH5015765, which
      showed high affinity for Hsp90 and antitumor activity in human cancer xenograft
      mouse models.

PMID- 21875804
TI  - Synthesis and anticonvulsant activity of new 1-[2-oxo-2-(4-phenylpiperazin-1
      yl)ethyl]pyrrolidine-2,5-diones.
AB  - Twenty-two new 1-[2-oxo-2-(4-phenylpiperazin-1-yl)ethyl]pyrrolidine-2,5-diones
      were synthesized and tested for anticonvulsant activity. Initial anticonvulsant
      screening was performed using standard maximal electroshock (MES) and
      subcutaneous pentylenetetrazole (scPTZ) screens in mice. Several compounds were
      tested additionally in the 6-Hz psychomotor seizure model. The neurotoxicity was
      determined applying the rotarod test. Excluding one compound, all other molecules
      were found to be effective in at least one seizure model. The most active were 1
      (2-oxo-2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)pyrrolidine-2,5-dione
      (14), 1-{2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}-3-methylpyrrolidine-2,5
      dione (17), 1-{2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}-3,3
      dimethylpyrrolidine-2,5-dione (23) and 3,3-dimethyl-1-(2-oxo-2-{4-[3
      (trifluoromethyl)phenyl]piperazin-1-yl}ethyl)pyrrolidine-2,5-dione (26). These
      compounds showed high activity in the 6-Hz psychomotor seizure test as well as
      were active in the maximal electroshock and subcutaneous pentylenetetrazole (14
      and 23) screens. Initial SAR studies for anticonvulsant activity have been
      discussed.

PMID- 21875806
TI  - Structure-activity relationship study of pyridazine derivatives as glutamate
      transporter EAAT2 activators.
AB  - Excitatory amino acid transporter 2 (EAAT2) is the major glutamate transporter
      and functions to remove glutamate from synapses. A thiopyridazine derivative has
      been found to increase EAAT2 protein levels in astrocytes. A structure-activity
      relationship study revealed that several components of the molecule were required
      for activity, such as the thioether and pyridazine. Modification of the
      benzylthioether resulted in several derivatives (7-13, 7-15 and 7-17) that
      enhanced EAAT2 levels by >6-fold at concentrations < 5 MUM after 24h. In
      addition, one of the derivatives (7-22) enhanced EAAT2 levels 3.5-3.9-fold after
      24h with an EC(50) of 0.5 MUM.

PMID- 21875807
TI  - Enhanced ROS production and cell death through combined photo- and sono
      activation of conventional photosensitising drugs.
AB  - A combination of light and ultrasound activation of two conventional
      photosensitising drugs, methylene blue and rose bengal, was shown to generate
      higher levels of reactive oxygen species (ROS) and lower LD50 values than either
      light or ultrasound activation alone.

PMID- 21875805
TI  - Synthesis of a new trifluoromethylketone analogue of l-arginine and contrasting
      inhibitory activity against human arginase I and histone deacetylase 8.
AB  - As part of our continuing search for new amino acid inhibitors of metalloenzymes,
      we now report the synthesis and biological evaluation of the
      trifluoromethylketone analogue of L-arginine, (S)-2-amino-8,8,8-trifluoro-7-oxo
      octanoic acid (10). While this novel amino acid was initially designed as a
      potential inhibitor of human arginase I, it exhibits no measurable inhibitory
      activity against this enzyme. Surprisingly, however, 10 is a potent inhibitor of
      human histone deacetylase 8, with IC(50)=1.5 +/- 0.2 MUM. Additionally, 10 weakly
      inhibits the related bacterial enzyme, acetylpolyamine amidohydrolase, with
      IC(50)=110 +/- 30 MUM. The lack of inhibitory activity against human arginase I
      may result from unfavorable interactions of the bulky trifluoromethyl group of 10
      in the constricted active site. Since the active site of histone deacetylase 8 is
      less constricted, we hypothesize that it accommodates 10 as the gem-diol, which
      mimics the tetrahedral intermediate and its flanking transition states in
      catalysis. Therefore, we suggest that 10 represents a new lead in the design of
      an amino acid or peptide-based inhibitor of histone deacetylases with simpler
      structure than previously studied trifluoromethylketones.

PMID- 21875808
TI  - Synthesis and pharmacological evaluation of 1-alkyl-N-[2-ethyl-2-(4
      fluorophenyl)butyl]piperidine-4-carboxamide derivatives as novel antihypertensive
      agents.
AB  - We synthesized and evaluated inhibitory activity against T-type Ca(2+) channels
      for a series of 1-alkyl-N-[2-ethyl-2-(4-fluorophenyl)butyl]piperidine-4
      carboxamide derivatives. Structure-activity relationship studies have revealed
      that dialkyl substituents at the benzylic position play an important role in
      increasing inhibitory activity. Oral administration of N-[2-ethyl-2-(4
      fluorophenyl)butyl]-1-(2-phenylethyl)piperidine-4-carboxamide (20d) lowered blood
      pressure in spontaneously hypertensive rats without inducing reflex tachycardia,
      which is often caused by traditional L-type Ca(2+) channel blockers.

PMID- 21875809
TI  - Constitutively expressed DHAR and MDHAR influence fruit, but not foliar ascorbate
      levels in tomato.
AB  - Vitamin C (L-ascorbate, AsA) is an essential nutrient required in key metabolic
      functions in humans and must be obtained from the diet, mainly from fruits and
      vegetables. Given its importance in human health and plant physiology we sought
      to examine the role of the ascorbate recycling enzymes monodehydroascorbate
      reductase (MDHAR) and dehydroascorbate reductase (DHAR) in tomato (Solanum
      lycopersicum), an economically important fruit crop. Cytosolic-targeted tomato
      genes Mdhar and Dhar were cloned and over-expressed under a constitutive promoter
      in tomato var. Micro-Tom. Lines with increased protein levels and enzymatic
      activity were identified and examined. Mature green and red ripe fruit from DHAR
      over-expressing lines had a 1.6 fold increase in AsA content in plants grown
      under relatively low light conditions (150 MUmol m(-2) s(-1)). Conversely, MDHAR
      over-expressers had significantly reduced AsA levels in mature green fruits by
      0.7 fold. Neither over-expressing line had altered levels of AsA in foliar
      tissues. These results underscore a complex regulation of the AsA pool size in
      tomato.

PMID- 21875810
TI  - Oral fibrous histiocytoma and its angiomatoid variant.
AB  - Fibrous histiocytomas are uncommon mesenchymal tumours of the soft tissue in the
      head and neck region. We report two cases that occurred in the oral cavity, one
      of a benign fibrous histiocytoma (BFH) and another of an angiomatoid variant of
      fibrous histiocytoma (AFH). BFH is a benign neoplasm composed of cells with
      fibroblastic and histiocytic characteristics, while AFH is considered as a
      distinct type of fibrous histiocytoma with an intermediate malignancy grade that
      combines features of both fibrohistiocytic and vascular neoplasm. We describe the
      clinicopathological and histological characteristics of these lesions to clarify
      and facilitate their diagnosis. In the BFH case, the surgical specimen had many
      histiocytes positive for lysozime, whereas the AFH cells showed positivity for
      endothelial cell marker (anti-CD34 antibody). In both cases the tumours were
      positive for fibronectin and negative for S100 and SMA. Ki-67.
      Immunohistochemistry was performed in all cases to reveal the different mitotic
      activity between AFH and BFH tumour cells. Finally, differential diagnoses and
      therapeutic treatments are discussed.

PMID- 21875812
TI  - Biosimilars clinical development program: confirmatory clinical trials: a
      virtual/simulated case study comparing equivalence and non-inferiority
      approaches.
AB  - As part of long term commitment of the Biologicals and Vaccines Committee (B&V)
      of the International Federation of Pharmaceutical Manufacturers and Association
      (IFPMA) to provide expert input to the WHO on their recently finalized GUIDELINES
      ON EVALUATION OF SIMILAR BIOTHERAPEUTIC PRODUCTS (SBPs), and in response to WHO's
      request, the IFPMA B&V prepared a clinical case study at a recent WHO workshop in
      Seoul, Korea. The case study, presented by Mark Fletcher on behalf of B&V,
      involved a model scenario for a clinical efficacy trial to support the approval
      of a Similar Biotherapeutic Product (SBP) as part of the required comparative
      clinical program against a Reference Biotherapeutic Product (RBP). A key goal was
      to understand and illustrate key clinical and statistical principles, and
      considerations described in the WHO Guidance for regulatory authorities when
      designing and implementing WHO guidelines and post-approval regulatory oversight
      for SBPs. Using this model SBP/RBP pair, an interactive discussion was carried
      out among the workshop participants on the pros and cons of using equivalence vs.
      non-inferiority designs to assess the two products' similarity. Through
      discussion of the case, the complexity of demonstrating similar efficacy and
      safety of a SBP vs. RBP for biotherapeutic products is outlined and discussed in
      the context of the key principles laid out in the recently published WHO
      GUIDELINES ON EVALUATION OF SIMILAR BIOTHERAPEUTIC PRODUCTS (SBPs). The exercise
      illustrates the need for a case-by-case approach when interpreting clinical data
      from SBP dossiers to adequately assure similar efficacy and safety of SBPs for
      any studied indication.

PMID- 21875811
TI  - Measurement of width and distance of the posterior border of the deep lateral
      orbital wall using computed tomography.
AB  - INTRODUCTION: Techniques of orbital decompression for Graves' ophthalmopathy
      continue to evolve. Recently the deep lateral orbital wall has been proposed as
      the most effective and safe site for a decompression procedure associated with
      the least complications. Anatomic variations with structures like the middle
      cranial fossa render decompression of the lateral wall more logical. We aimed to
      understand the anatomic localization and appearance of the lateral orbital wall
      by measuring the width and distance of the lateral wall on computed tomography
      (CT). MATERIAL AND METHODS: The medical records of all patients who underwent
      orbital CT scans for ocular trauma or for confirmation of orbital disease at the
      Korea University hospital between January 2005 and May 2008 were reviewed
      retrospectively. All patients had been scanned with the same CT scanner (Philips
      Brilliance 64 channel CT; Philips Healthcare Systems). Patients who had normal
      orbits bilaterally were included in this study. The cut in which the lateral
      rectus muscle was longest and the lateral bony orbit was thickest was selected
      from the axial and coronal slices. The point where the lateral rectus muscle
      contacted the the bone was measured on this axial slice. The width of the lateral
      wall was measured at the level of superior border of the lateral rectus muscle on
      thickest part of the coronal slice. RESULTS: A total of 334 orbits (167 patients)
      were included. Patients ranged in age from 7 years to 78 years (median age 41.1
      years). The average distance of the lateral wall was 26.0 mm OD and 25.0 mm OS.
      The average width of the lateral wall was 16.0 mm OD 16.2 mm OS. There was no
      statistically significant difference between right and left. The patients were
      divided into 8 age groups by decades. There was no statistically significant
      difference between the groups in either measurement. CONCLUSION: In this study,
      we measured the average width and length of the thickest segment of the greater
      wing of the sphenoid, which can be used as anatomic guidelines during deep
      lateral orbital decompression surgery, and the basic standard value of the
      lateral orbital wall.

PMID- 21875813
TI  - Predictors of sleep characteristics among women in southeast Texas.
AB  - PURPOSE: This study examined psychological and sociodemographic predictors of
      self-reported sleep characteristics including sleep duration, quality, and
      perceived adequacy of sleep among Hispanic and non-Hispanic women of low
      socioeconomic status. METHOD: Cross-sectional survey data were analyzed from
      2,670 women ages 18 to 55 (74% Hispanic, 18% non-Hispanic White, 8% non-Hispanic
      Black) participating in a cancer prevention study in southeast Texas. RESULTS:
      Women reported sleeping 7.1 hours per night on average; however, nearly 45% were
      short (<=6; 35.3%) or long (>=9; 9.5%) sleepers. Sleep quality was rated less
      than "good" for 43.7% of the total sample, and 22.5% reported adequate sleep
      "none" or "a little" of the time. Multivariable analyses identified different
      demographic and psychological predictors for the sleep characteristics; decreased
      sleep adequacy was associated with parity, depressive symptoms, stress, and
      anxiety (R(2) = 0.11); short sleep duration with age, education, and depressive
      symptoms (R(2) = 0.07); and poor sleep quality with ethnicity, marital and
      employment status, public housing accommodation, smoking status, income,
      acculturation, social desirability, depressive symptoms, stress, and anxiety
      (R(2) = 0.18). Separate analyses of the Hispanic subsample born in the United
      States versus elsewhere revealed differences in all sleep characteristics. In
      multivariable analyses, similar predictors of sleep quality and duration emerged,
      but only depressive symptoms, anxiety, and age were associated with sleep
      adequacy. CONCLUSION: Women of lower socioeconomic groups and Hispanic ethnicity
      may suffer poor quality sleep. A complex and distinct array of factors are
      associated with sleep quality, duration, and adequacy. The relationship between
      sleep and health and the growing U.S. Hispanic population highlight the
      importance of this and future research.

PMID- 21875815
TI  - N-butyl cyanoacrylate embolization as the primary treatment of acute
      hemodynamically unstable lower gastrointestinal hemorrhage.
AB  - PURPOSE: To evaluate N-butyl cyanoacrylate (NBCA) embolization as the primary
      treatment for patients with severe and acute hemodynamically unstable lower
      gastrointestinal bleeding. MATERIALS AND METHODS: Twenty-seven patients with
      acute, unstable hemodynamics caused by lower gastrointestinal bleeding underwent
      therapeutic NBCA microcatheter embolization over a period of 27 months. The
      inclusion criteria were hematochezia or melena and hypotension refractory to
      conservative treatment and requiring blood transfusion. Bleeding was localized to
      the rectum, colon, or small intestine in all nine such cases. Fifteen patients
      had severe underlying comorbidities, including sepsis, respiratory failure,
      malignancy, or renal failure. RESULTS: The procedure was technically successful
      in all patients. Twenty-six patients were treated solely with NBCA, and one
      required microcoil embolization. Embolization was performed at the level of the
      arteria recta or as close as possible to the point of bleeding. Immediate
      hemostasis occurred in all cases. Four patients experienced repeat hemorrhage,
      one of whom died. The other three were treated successfully with repeat NBCA
      embolization. None of the surviving patients had evidence of bowel ischemia. In
      addition, none of the patients with severe underlying disease died during the
      follow-up period (range, 3 mo to 2 y). CONCLUSIONS: The present findings suggest
      that NBCA embolization may be a safe alternative treatment for the management of
      lower gastrointestinal bleeding. Further studies are warranted to confirm the
      findings.

PMID- 21875814
TI  - Imaging guidance with C-arm CT: prospective evaluation of its impact on patient
      radiation exposure during transhepatic arterial chemoembolization.
AB  - PURPOSE: To prospectively evaluate the impact of C-arm CT on radiation exposure
      to hepatocellular carcinoma (HCC) patients treated by chemoembolization.
      MATERIALS AND METHODS: Patients with HCC (N = 87) underwent digital subtraction
      angiography (DSA; control group) or combined C-arm CT/DSA (test group) for
      chemoembolization. Dose-area product (DAP) and cumulative dose (CD) were measured
      for guidance and treatment verification. Contrast agent volume and C-arm CT
      utility were also measured. RESULTS: The marginal DAP increase in the test group
      was offset by a substantial (50%) decrease in CD from DSA. Use of C-arm CT
      allowed reduction of DAP and CD from DSA imaging (P = .007 and P = .017).
      Experienced operators were more efficient in substituting C-arm CT for DSA,
      resulting in a negligible increase (7.5%) in total DAP for guidance, compared
      with an increase of 34% for all operators (P = .03). For treatment verification,
      DAP from C-arm CT exceeded that from DSA, approaching that of conventional CT.
      The test group used less contrast medium (P = .001), and C-arm CT provided
      critical or supplemental information in 20% and 17% of patients, respectively.
      CONCLUSIONS: Routine use of C-arm CT can increase stochastic risk (DAP) but
      decrease deterministic risk (CD) from DSA. However, the increase in DAP is
      operator-dependent, thus, with experience, it can be reduced to under 10%. C-arm
      CT provides information not provided by DSA in 33% of patients, while decreasing
      the use of iodinated contrast medium. As with all radiation-emitting modalities,
      C-arm CT should be used judiciously.

PMID- 21875817
TI  - Rewarding performance feedback alters reported time of action.
AB  - Past studies have shown that the perceived time of actions is retrospectively
      influenced by post-action events. The current study examined whether rewarding
      performance feedback (even when false) altered the reported time of action. In
      Experiment 1, participants performed a speeded button press task and received
      monetary reward for a presumed "fast," or a monetary punishment for a presumed
      "slow" response. Rewarded trials resulted in the false perception that the
      response action occurred earlier than punished trials. In Experiments 2 and 3,
      the need for a speeded response and reward were independently manipulated in
      order to decouple the cognitive and reward components in the feedback signal.
      When tested independently, neither variable affected the judged time of action.
      We conclude that meaningful feedback (fast or slow) is only used when made
      salient by reward, to modulate the judged time of an action.

PMID- 21875818
TI  - Magnetic field anisotropy based MR tractography.
AB  - Non-invasive measurements of structural orientation provide unique information
      regarding the connectivity and functionality of fiber materials. In the present
      study, we use a capillary model to demonstrate that the direction of fiber
      structure can be obtained from susceptibility-induced magnetic field anisotropy.
      The interference pattern between internal and external magnetic field gradients
      carries the signature of the underlying anisotropic structure and can be measured
      by MRI-based water diffusion measurements. Through both numerical simulation and
      experiments, we found that this technique can determine the capillary orientation
      within 3 degrees . Therefore, susceptibility-induced magnetic field anisotropy
      may be useful for an alternative tractography method when diffusion anisotropy is
      small at higher magnetic field strength without the need to rotate the subject
      inside the scanner.

PMID- 21875819
TI  - Emulation of petroleum well-logging D-T2 correlations on a standard benchtop
      spectrometer.
AB  - An experimental protocol is described that allows two-dimensional (2D) nuclear
      magnetic resonance (NMR) correlations of apparent diffusion coefficient D(app)
      and effective transverse relaxation time T(2,eff) to be acquired on a bench-top
      spectrometer using pulsed field gradients (PFG) in such a manner as to emulate
      D(app)-T(2,eff) correlations acquired using a well-logging tool with a fixed
      field gradient (FFG). This technique allows laboratory-scale NMR measurements of
      liquid-saturated cored rock to be compared directly to logging data obtained from
      the well by virtue of providing a comparable acquisition protocol and data
      format, and hence consistent data processing. This direct comparison supports the
      interpretation of the well-logging data, including a quantitative determination
      of the oil/brine saturation. The D-T(2) pulse sequence described here uses two
      spin echoes (2SE) with a variable echo time to encode for diffusion. The
      diffusion and relaxation contributions to the signal decay are then deconvolved
      using a 2D numerical inversion. This measurement allows shorter relaxation time
      components to be probed than in conventional diffusion measurements. A brief
      discussion of the numerical inversion algorithms available for inverting these
      non-rectangular data is included. The PFG-2SE sequence described is well suited
      to laboratory-scale studies of porous media and short T(2) samples in general.

PMID- 21875820
TI  - Dosimetric impact of fiducial markers in patients undergoing photon beam
      radiation therapy.
AB  - Fiducial markers are widely used in image-guided radiation therapy to correct for
      setup error and organ motion. These markers, however, can cause dose
      perturbations in the target volume for patients undergoing external-beam
      radiation therapy. The goal of this study was to determine the dosimetric impact
      of various types of fiducial markers commonly used in patients receiving photon
      radiation therapy. Monte Carlo simulations based on a newly developed EGSnrcMP
      user code were used to investigate three types of gold fiducial markers and a
      carbon marker. A single photon field with each fiducial in various orientations
      and two parallel-opposed beams were simulated at 6-MV and 18-MV energies. The
      results indicated that dose perturbations depended on marker size, material, and
      orientation, as well as on incident beam energy. Maximum dose perturbations were
      found for a single 6-MV beam. The increase in dose reached a factor of 1.58 near
      the upstream surface of the gold marker because of electron backscatter. At the
      downstream surface, the dose was reduced to a factor of 0.53 at the same point
      without the marker. For the 18-MV beam, the maximum dose factor was 1.48 and the
      minimum dose factor was 0.66. For the two parallel-opposed beams, the maximum
      dose reduction was within 5% at 6 MV and 2% at 18 MV. Dose enhancement, however,
      remained significant, reaching factors of 1.20 and 1.33 for the two energies near
      the fiducial surface. Carbon fiducials caused dose perturbations of only ~1%.

PMID- 21875821
TI  - DOCK8 deficiency, T cell receptor excision circles and newborn screening.

PMID- 21875822
TI  - Partial penile reconstruction following fat augmentation with anterolateral thigh
      perforator flap.
AB  - Augmentation phalloplasty of the normal penis although is gaining popularity
      among a subgroup of men, is not free of complications. A 27 years old healthy man
      with normal functioning penis underwent a lipofilling penile augmentation. The
      procedure was complicated by a post-operative haematoma and infection resulting
      in a full thickness dorsal penile skin necrosis and a pedicled anterolateral
      thigh (ALT) perforator flap was required for reconstruction. His presentation,
      operation and final outcome are reported and the possible options for
      reconstruction are discussed.

PMID- 21875823
TI  - Acellularized cadaver dermis for reconstruction of complex scalp defects.

PMID- 21875824
TI  - Examining reduction mammaplasty in Hispanic and African American populations: a
      changing landscape in American plastic surgery.

PMID- 21875825
TI  - Training, competency, and certification in cardiac CT: a summary statement from
      the Society of Cardiovascular Computed Tomography.
AB  - Training and competency criteria in cardiac CT were developed to guide
      practitioners in the process of achieving and maintaining skills in performing
      and interpreting cardiac CT studies. Appropriate training and eventual
      certification in cardiac CT angiography may be obtained by adhering to the
      recommendations for competency as set forth by either the American College of
      Cardiology Foundation (ACCF) or the American College of Radiology (ACR).
      Competency under either pathway requires both knowledge and experience-based
      components, with benchmarks set for level of experience on the basis of the
      extent of training experience. Although these recommended parameters are
      substantial, meeting these training criteria does not guarantee competence or
      expertise, which is the responsibility of the individual practitioner and may
      require further training and experience. Separate from satisfying initial
      training for the achievement of competency, certification in cardiac CT may be
      achieved through formal certification under the Certification Board of
      Cardiovascular Computed Tomography. Eligibility for certification generally
      follows the ACCF/American Heart Association Level 2 or ACR competency pathways.
      The ACR also conducts a certificate program related to advanced proficiency in
      cardiac CT. This official document of the Society of Cardiovascular Computed
      Tomography summarizes the present criteria for competency and certification in
      the field of cardiac CT.

PMID- 21875826
TI  - New iterative reconstruction techniques for cardiovascular computed tomography:
      how do they work, and what are the advantages and disadvantages?
AB  - The radiation doses associated with diagnostic CT scans has recently come under
      scrutiny. In the process of developing protocols with lower doses, it has become
      apparent that images reconstructed with a filtered back projection (FBP)
      technique are often inadequate. Although very fast and robust, FBP images are
      prone to high noise, streak artifacts and poor low contrast detectability in low
      dose situations. Manufacturers of CT equipment have responded to this limitation
      by developing new image reconstruction techniques that derive more information
      from the data set. These techniques are based on the use of maximum likelihood
      algorithms and are referred to at iterative reconstructions. This iterative
      process can be used on the slice data alone, a combination of raw and slice data
      or on the raw data alone. The latter approach, which is referred to as model
      based iterative reconstruction, is the most computationally demanding as it
      models the entire process, from the shape of the focal spot on the anode, the
      shape of the emerging x-ray beam, the three-dimensional interaction of the beam
      with the voxel in the patient and the two-dimensional interation of the beam with
      the detector. This article discusses the fundamentals of iterative reconstruction
      techniques, the pros and cons of the various manufacturer approaches and specific
      applications, especially to cardiovascular CT.

PMID- 21875827
TI  - Reproducibility of left and right ventricular mass measurements with cardiac CT.
AB  - BACKGROUND: Cardiac CT provides volumetric data that enables characterization of
      the myocardium. OBJECTIVE: We evaluated intraobserver, interobserver, and
      interstudy reproducibility of left ventricular (LV) and right ventricular (RV)
      mass quantification with cardiac CT. METHODS: Thirty-eight patients who underwent
      cardiac CT twice within 365 days were included in this analysis. Functional
      reconstructions in 10% steps throughout the R-R interval and axial 1.5-mm
      sections were used. Semiautomatic contour detection was used to trace epicardial
      and endocardial borders in all cardiac phases for calculation of LV and RV
      ejection fraction, end-diastolic volume, end-systolic volume, cardiac output,
      stroke volume, and ventricular mass. For each study 2 observers measured LV and
      RV mass twice. RESULTS: LV mass parameters derived from semiautomatic contour
      detection algorithm had excellent intraobserver (r = 1.00), interobserver (r =
      0.99), and interstudy (r = 0.99) reproducibility (P < 0.0001). Average end
      diastolic LV mass was 146.2 +/- 42.9 g at the first CT study and 146.8 +/- 44.4 g
      at the second study. For measuring RV mass, reproducibility was good on all
      levels (r = 0.78, r = 0.78, and r = 0.68, respectively, with an average end
      diastolic mass of 25.7 +/- 5.8 g at the first study and 24.4 +/- 4.8 g at the
      second study. CONCLUSION: Quantification of LV mass at cardiac CT with the
      threshold-based, region-growing semiautomatic segmentation analysis software
      evaluated here is highly observer independent and reproducible. This largely
      holds true for the estimation of RV mass as well; however, further improvements
      are needed to optimize reproducibility for RV mass quantification.

PMID- 21875828
TI  - Exercise programming and counseling preferences of breast cancer survivors during
      or after radiation therapy.
AB  - PURPOSE/OBJECTIVES: To explore exercise programming and counseling preferences
      and exercise-related beliefs in breast cancer survivors during and after
      radiation therapy, and to compare differences based on treatment and insurance
      status. DESIGN: Cross-sectional survey. SETTING: Ambulatory cancer center in a
      rural community in eastern North Carolina. SAMPLE: 91 breast cancer survivors
      during or after radiation therapy. METHODS: The researchers administered the
      questionnaire to participants. MAIN RESEARCH VARIABLES: Exercise programming and
      counseling preferences and exercise beliefs moderated by treatment status (on
      treatment, early, and late survivors) and insurance status (Medicaid, non
      Medicaid). FINDINGS: Chi-square analyses indicated that fewer Medicaid users were
      physically active and reported health benefits as an advantage of exercise
      compared to non-Medicaid users (p < 0.05). In addition, more Medicaid users
      preferred exercise programming at their cancer center compared to non-Medicaid
      users (p < 0.05). More on-treatment and early survivors listed health benefits as
      advantages to exercise, but fewer indicated weight control as an advantage
      compared to late survivors (p < 0.05). Early survivors were more likely than on
      treatment survivors to indicate that accessible facilities would make exercising
      easier for them (p < 0.05). CONCLUSIONS: Medicaid users are less active, less
      likely to identify health benefits as an advantage for exercising, and more
      likely to prefer cancer center-based exercise programming compared to non
      Medicaid users. In addition, on-treatment and early survivors are more likely to
      list health benefits and less likely to indicate weight control as advantages of
      exercising compared to late survivors. IMPLICATIONS FOR NURSING: The low activity
      levels of Medicaid users may be best targeted by providing cancer center-based
      exercise programming. Exercise interventions may be most effective if tailored to
      the unique needs of treatment status.

PMID- 21875829
TI  - Advancing the psychosocial care of patients with cancer at life's end: a global
      nursing response.

PMID- 21875830
TI  - Hope in adults with cancer: state of the science.
AB  - PURPOSE/OBJECTIVES: To synthesize the literature regarding research on hope in
      adults with cancer. DATA SOURCES: CINAHL Plus(r) and PsycINFO databases. DATA
      SYNTHESIS: Sixteen articles published from 2005-2009 met the criteria for review.
      The literature was organized according to Oncology Nursing Society levels of
      evidence. Research studies on hope in adults with cancer were analyzed,
      critiqued, and synthesized. CONCLUSIONS: Research evidence continues to grow
      regarding descriptions of hope and hope attributes in adults with cancer.
      Although nursing intervention programs have demonstrated positive effects on hope
      in adults newly diagnosed with cancer, those with a first cancer recurrence, the
      terminally ill, and survivors of childhood cancer, current studies are small and
      additional research is indicated. IMPLICATIONS FOR NURSING: Opportunities exist
      to explain the dynamic process of hope, develop hope interventions that are
      tailored to meet the developmental needs of adults with cancer, and study
      existing nursing programs that support hope using larger samples in randomized,
      controlled trials.

PMID- 21875831
TI  - Sexual well-being among survivors of non-Hodgkin lymphoma.
AB  - PURPOSE/OBJECTIVES: To describe sexual well-being among non-Hodgkin lymphoma
      (NHL) survivors. DESIGN: Descriptive, correlational, cross-sectional study.
      SETTING: NHL survivors identified via the Los Angeles County Cancer Surveillance
      Program. SAMPLE: 222 NHL survivors two- to five-years postdiagnosis. METHODS:
      Data were collected via mailed questionnaire. Multivariate models were used to
      examine sexual well-being. MAIN RESEARCH VARIABLES: Three indices of sexual well
      being were examined in relation to sociodemographic and medical variables:
      participation in sexual activity, satisfaction with sex life, and sexual
      function. FINDINGS: Most NHL survivors were participating in sexual activity;
      however, more than half were dissatisfied with their sex life. A substantial
      minority "usually or always" experienced problems with sexual function.
      Associations between study variables and outcomes differed across indices of
      sexual well-being and by gender; older age was associated with decreased
      participation, decreased satisfaction, and impaired sexual function for men as
      well as with decreased participation for women. Poorer physical functioning was
      associated with decreased participation for men and women as well as poorer
      sexual function for women. Finally, poorer mental functioning was associated with
      less satisfaction and poorer sexual function for men and women; shorter times
      since diagnosis were associated with poorer sexual function for women.
      CONCLUSIONS: Most NHL survivors were sexually active, but many reported
      difficulties with satisfaction and function. Sexual well-being is a multifaceted
      construct that requires continued attention throughout survivorship. IMPLICATIONS
      FOR NURSING: Oncology nurses are in an excellent position to ensure that
      survivors' sexual concerns are addressed. Survivorship care plans may help to
      facilitate communication about survivors' sexual well-being.

PMID- 21875832
TI  - A career of "why?" and "why not?".

PMID- 21875833
TI  - Disturbed sleep in pediatric patients with leukemia: the potential role of
      interleukin-6 (-174GC) and tumor necrosis factor (-308GA) polymorphism.
AB  - PURPOSE/OBJECTIVES: To explore an association between sleep quality in children
      and adolescents undergoing therapy for acute lymphoblastic leukemia (ALL) and
      polymorphisms in two proinflammatory cytokines, interleukin-6 (IL-6) and tumor
      necrosis factor (TNF). DESIGN: Retrospective exploratory analysis using data from
      a multi-institutional prospective study comparing objective sleep measures by
      actigraphy over 10 days with retrospective genotyping of IL-6 (-174GC) and TNF (
      308GA). SETTING: Pediatric oncology centers in the southeastern and southwestern
      United States and in Canada. SAMPLE: 88 children or adolescents with ALL.
      METHODS: Secondary analysis of 88 patients (ages 5-18) with sleep quality
      measured by actigraphy over 10 days in their home environment and retrospective
      DNA genotyping. MAIN RESEARCH VARIABLES: Sleep variables and genotype. FINDINGS:
      IL-6 promoter (-174G>C) C allele was associated with fewer total daily sleep
      minutes (p = 0.028) and fewer daily nap minutes (p < 0.01). Patients with the TNF
      genotype AA had 28.2 more minutes of wake after sleep onset (p = 0.015), 3.4 more
      nocturnal wake episodes (p = 0.026), and a 5% lower sleep efficiency rate (p =
      0.03) than their GA genotype counterparts. CONCLUSIONS: Patients with the TNF (
      308G>A) or IL-6 (-174G>C) polymorphisms demonstrated disturbed sleep. This study
      is the first to find a relationship between these two cytokines and disturbed
      sleep in children and adolescents with cancer. IMPLICATIONS FOR NURSING:
      Disturbed sleep among pediatric patients with cancer is multifactoral and
      includes interactions among environment, medications, and genotype. Additional
      research should explore serum proinflammatory cytokine levels and the influence
      of mood and worry on sleep.

PMID- 21875834
TI  - Informal caregiving in patients with brain tumors.
AB  - PURPOSE/OBJECTIVES: To explore the experience of informal caregivers of patients
      with a primary brain tumor by identifying themes of the caregiving experience
      specific to this population. RESEARCH APPROACH: Qualitative study employing
      Parse's descriptive exploratory method. SETTING: National Cancer Institute
      designated comprehensive cancer center in a major city in the southern United
      States. PARTICIPANTS: 20 patients with primary brain tumors and their caregivers.
      METHODOLOGIC APPROACH: Data collection involved a tape-recorded dialogue with
      caregivers using Story Theory. Patient and caregiver demographic information was
      collected. MAIN RESEARCH VARIABLES: Concepts of commitment, expectation
      management, role negotiation, self-care, new insight, and role support. FINDINGS:
      Caregivers of patients with primary brain tumors used the energy sources
      identified by the Model of Informal Caregiving Dynamics. Commitment is sustained
      through enduring patient cognitive and behavioral decline. Expectations are based
      on a realistic understanding of the disease trajectory and known mortality, and
      allow caregivers to hope for the ability to manage declining patients. Caregivers
      express difficulty in gauging the behavior of cognitively impaired patients.
      Healthcare providers support caregivers by supplying information and listening to
      caregivers' stories. In contrast to a similar study involving caregivers of bone
      marrow transplantation recipients, these caregivers reported negative
      perceptions. CONCLUSIONS: Commitment, expectation management, role negotiation,
      self-care, new insight, and role support motivate informal caregivers of patients
      with primary brain tumors in a unique way. INTERPRETATION: Healthcare providers
      can support the caregiving experience by validating efforts, providing
      information, and listening to frustrations. Additional research should explore
      interventions aimed at assisting caregivers.

PMID- 21875836
TI  - Are you a mid-level provider, a physician extender, or a nurse?

PMID- 21875835
TI  - Nausea, pain, fatigue, and multiple symptoms in hospitalized children with
      cancer.
AB  - PURPOSE/OBJECTIVES: To describe the prevalence, frequency, severity, and distress
      of multiple symptoms in hospitalized children with cancer and to examine the
      overall symptom scores and global distress in patients reporting nausea, pain,
      and fatigue. DESIGN: Descriptive design with repeated measures. SETTING:
      Inpatient pediatric hematology-oncology unit. SAMPLE: 39 inpatients (ages 10-17)
      diagnosed with cancer. METHODS: Five-day data collection using the Memorial
      Symptom Assessment Scale (MSAS) Pediatric 10-18. MAIN RESEARCH VARIABLES: Thirty
      one symptoms included in the MSAS Pediatric 10-18. FINDINGS: The most common
      symptoms (prevalence greater than 34%) were nausea, fatigue, decreased appetite,
      pain, and feeling drowsy. Differences in symptom experiences occurred in the
      presence of nausea, pain, and fatigue compared to days when they were not
      reported (p < 0.001). Prevalence of pain and fatigue symptoms decreased over the
      five days (p < 0.05), but not nausea (p > 0.05). CONCLUSIONS: Nausea, pain, and
      fatigue were among the most prevalent symptoms in hospitalized children with
      cancer; however, the most prevalent symptoms were not always the most severe or
      distressing. The presence of these symptoms significantly impacted symptom
      experience, including total burden of symptoms experienced by the child (i.e.,
      global distress). IMPLICATIONS FOR NURSING: Additional examination of symptom
      management is needed. Nausea and its related symptoms have received little
      attention and more effective interventions are warranted. Multidimensional scales
      and the use of handheld electronic devices to track symptoms may be used to
      provide a more comprehensive assessment and treatment of symptoms.

PMID- 21875838
TI  - A successful evidence-based practice model in an acute care setting.

PMID- 21875839
TI  - Nutritional challenges during treatment for lung cancer.

PMID- 21875840
TI  - Coping resources and self-rated health among Latina breast cancer survivors.
AB  - PURPOSE/OBJECTIVES: To examine relationships between coping resources and self
      rated health among Latina breast cancer survivors. DESIGN: Cross-sectional
      telephone survey. SETTING: Four northern California counties. SAMPLE: 330 Latina
      breast cancer survivors within one to five years of diagnosis. METHODS: Telephone
      survey conducted by bilingual and bicultural interviewers. MAIN RESEARCH
      VARIABLES: Predictors were sociodemographic and clinical factors, cancer self
      efficacy, spirituality, and social support from family, friends, and oncologists.
      Outcomes were functional limitations and self-rated health. FINDINGS: Twenty-two
      percent of women reported functional limitations (n = 73) and 27% reported poor
      or fair self-rated health (n = 89). Unemployment (adjusted odds ratio [AOR] =
      7.06; 95% confidence interval [CI] [2.04, 24.46]), mastectomy (AOR = 2.67; 95% CI
      [1.06, 6.77]), and comorbidity (AOR = 4.09; 95% CI [1.69, 9.89]) were associated
      with higher risk of functional limitations; cancer self-efficacy had a protective
      effect (AOR = 0.4, 95% CI [0.18, 0.9]). Comorbidity was associated with higher
      risk of poor or fair self-rated health (AOR = 4.95; 95% CI [2.13, 11.47]); cancer
      self-efficacy had a protective effect (AOR = 0.3; 95% CI [0.13, 0.66]).
      CONCLUSIONS: Comorbidities place Latina breast cancer survivors at increased risk
      for poor health. Cancer self-efficacy deserves more attention as a potentially
      modifiable protective factor. IMPLICATIONS FOR NURSING: Nurses need to assess the
      impact of comorbidity on functioning and can reinforce patients' sense of control
      over cancer and clinician support.

PMID- 21875841
TI  - Factors and outcomes of decision making for cancer clinical trial participation.
AB  - PURPOSE/OBJECTIVES: To describe factors and outcomes related to the decision
      making process regarding participation in a cancer clinical trial. DESIGN: Cross
      sectional, descriptive. SETTING: Urban, academic, National Cancer Institute
      designated comprehensive cancer center in the mid-Atlantic United States. SAMPLE:
      197 patients with advanced gastrointestinal cancer. METHODS: Mailed survey using
      one investigator-developed instrument, eight instruments used in published
      research, and a medical record review. MAIN RESEARCH VARIABLES:  INDEPENDENT
      VARIABLES: disease context, sociodemographics, hope, quality of life, trust in
      healthcare system, trust in health professional, preference for research decision
      control, understanding risks, and information. DEPENDENT VARIABLES: decision to
      accept or decline research participation and satisfaction with this decision.
      FINDINGS: All of the factors within the Research Decision Making Model together
      predicted cancer clinical trial participation and satisfaction with this
      decision. The most frequently preferred decision-making style for research
      participation was shared (collaborative) (83%). CONCLUSIONS: Multiple factors
      affect decision making for cancer clinical trial participation and satisfaction
      with this decision. Shared decision making previously was an unrecognized factor
      and requires further investigation. IMPLICATIONS FOR NURSING: Enhancing the
      process of research decision making may facilitate an increase in cancer clinical
      trial enrollment rates. Oncology nurses have unique opportunities as educators
      and researchers to support shared decision making by those who prefer this method
      for deciding whether to accept or decline cancer clinical trial participation.

PMID- 21875842
TI  - Contextualizing the survivorship experiences of Haitian immigrant women with
      breast cancer: opportunities for health promotion.
AB  - PURPOSE/OBJECTIVES: To examine challenges faced by Haitian immigrant women
      managing a breast cancer diagnosis. RESEARCH APPROACH: Trained community health
      workers conducted focus groups with Haitian women who were breast cancer
      survivors. A grounded theory approach guided analysis of transcripts. SETTING: A
      large community-based organization in Miami, FL. PARTICIPANTS: 18 women took part
      in three focus groups. Participants were 40 years or older, were ethnically
      Haitian, and had been diagnosed with breast cancer 6-12 months prior to the
      study. METHODOLOGIC APPROACH: Data were collected as part of an ongoing community
      based participatory research initiative in Little Haiti, the largest enclave of
      Haitian settlement in Miami, FL. Community health workers, integral to the
      initiative, recruited participants through their extensive social networks and
      community contacts. MAIN RESEARCH VARIABLES: Screening knowledge, illness
      beliefs, social and economic consequences of a breast cancer diagnosis, and
      advice for breast health education. FINDINGS: Emergent themes suggest that
      Haitian breast cancer survivors face multiple challenges, including
      misperceptions about screening guidelines, disease etiology, and risk; a reduced
      capacity to earn a living because of physical debility; and diminished social
      support. CONCLUSIONS: Future research must continue to examine the impact of
      breast cancer on Haitian immigrant women and identify key strategies, such as
      community outreach and support programs, to improve their quality of life.
      INTERPRETATION: Nurses can play an essential role in such strategies by providing
      culturally relevant clinical care and partnering with community stakeholders to
      define the scope and focus of public health intervention.

PMID- 21875843
TI  - An Internet intervention for management of uncertainty during active surveillance
      for prostate cancer.
AB  - PURPOSE/OBJECTIVES: To provide preliminary data on an Internet intervention that
      incorporates cognitive reframing and self-management strategies to help older men
      undergoing active surveillance (AS) self-manage disease-related issues and
      improve quality of life (QOL). DESIGN: Single-subject design. SETTING: Two
      participating urologic practices at major academic medical centers in the
      northeastern United States. SAMPLE: 9 patients undergoing AS. METHODS: Baseline
      data were compared to data immediately after completion of the intervention and
      five weeks later. Telephone interviews were used to determine overall feasibility
      as well as the ease of use, user friendliness, and acceptability of the
      intervention in patients undergoing AS. MAIN RESEARCH VARIABLES: Self-efficacy,
      uncertainty, and QOL. FINDINGS: The results revealed change between baseline
      (time 1) and intervention completion (time 2) in the majority of variables, with
      a return toward baseline after the intervention (time 3). Ten of the 12 measures
      of intervention acceptability were met. The results showed positive trends in the
      impact of the intervention and good overall acceptability. CONCLUSIONS: The
      results of this pilot study will lead to further research aimed at helping men
      manage issues related to AS and improve QOL. IMPLICATIONS FOR NURSING: The
      intervention may reduce the overtreatment of prostate cancer in men who are
      clinically appropriate for this management option.

PMID- 21875844
TI  - Differences between women who pursued genetic testing for hereditary breast and
      ovarian cancer and their at-risk relatives who did not.
AB  - PURPOSE/OBJECTIVES: To (a) examine differences in appraisals of hereditary breast
      and ovarian cancer (HBOC), psychological distress, family environment, and
      decisional conflict between women who pursued genetic testing and their at-risk
      relatives who did not, and (b) examine correlations among appraisals of HBOC,
      psychological distress, family environment, and decisional conflict regarding
      genetic testing in these two cohorts of women. DESIGN: Descriptive, cross
      sectional cohort study. SETTING: Two clinics affiliated with a major research
      university in the midwestern United States. SAMPLE: 372 women aged 18 years and
      older. 200 pursued genetic testing for BRCA1 and BRCA2 mutations (probands) and
      172 of their female relatives who had a greater than 10% prior probability of
      being a mutation carrier but had not pursued testing. METHODS: After providing
      informed consent, probands and relatives were mailed self-administered
      questionnaires. MAIN RESEARCH VARIABLES: Perceived risk, knowledge of HBOC risk
      factors and modes of gene inheritance, perceived severity, perceived
      controllability, psychological distress, family relationships, family
      communication, and decisional conflict about genetic testing. FINDINGS: T tests
      revealed that probands perceived higher risk and had more psychological distress
      associated with breast cancer. Probands had more knowledge regarding risk factors
      and gene inheritance, and greater decisional conflict regarding genetic testing.
      Relatives reported higher perceived severity and controllability. No differences
      were observed in family relationships and family communication between probands
      and relatives. Pearson correlations revealed different patterns in knowledge,
      perceived controllability, family relationships, and decisional conflict between
      probands and relatives. CONCLUSIONS: Significant differences exist between women
      who pursue genetic testing and those who do not. The family environment
      influences adjustment to HBOC and decisions about genetic testing. IMPLICATIONS
      FOR NURSING: Enhancing the family communication process about HBOC can provide
      informational and emotional support to high-risk women and promote decision
      making about genetic testing.

PMID- 21875845
TI  - Influence of coping style on symptom interference among adult recipients of
      hematopoietic stem cell transplantation.
AB  - PURPOSE/OBJECTIVES: To investigate the influence of coping style on interference
      caused by a variety of common post-treatment symptoms after hematopoietic stem
      cell transplantation. DESIGN: Longitudinal; secondary analysis of data from the
      original study that examined health-related quality-of-life variables (e.g.,
      depression, well-being) in adult patients treated with conventional bone marrow
      transplantation or depleted T-cell bone marrow transplantation. SETTING: Fifteen
      university medical centers in the United States. SAMPLE: 105 adult recipients of
      hematopoietic stem cell transplantation. METHODS: Patients were assessed via
      telephone-based interviews for coping style at baseline and for symptom
      interference in daily living six months post-treatment. MAIN RESEARCH VARIABLES:
      Coping style and symptom interference. FINDINGS: Neither age nor gender predicted
      symptom interference, with the exception of chronic graft-versus-host disease,
      where older patients experienced more interference at six months, and breathing
      symptoms, for which women experienced more interference than men at six months.
      Avoidant coping style at baseline predicted increased interference from symptoms,
      but emotion-focused and instrumental coping styles did not predict decreased
      interference. CONCLUSIONS: A generalized avoidant coping style before treatment
      increased interference from common cancer symptoms six months after hematopoietic
      stem cell transplantation. IMPLICATIONS FOR NURSING: An intervention to teach
      alternate coping strategies should be implemented prior to treatment and tested
      for prevention of symptom-related life interference.

PMID- 21875850
TI  - Hepatocellular adenomas: correlation of MR imaging findings with pathologic
      subtype classification.
AB  - PURPOSE: To investigate the correlation between magnetic resonance (MR) imaging
      findings and pathologic subtype classification of hepatocellular adenoma (HCA).
      MATERIALS AND METHODS: This retrospective study was approved by the institutional
      review board, and the requirement for informed consent was waived. MR imaging
      studies of 61 lesions (48 patients; median age, 36 years) were available and were
      independently reviewed by two radiologists. Consensus readings on all morphologic
      and signal-intensity imaging features were obtained. Previously, these lesions
      had been classified on the basis of pathologic findings and immunohistochemical
      analysis. Fisher exact and chi2 tests were performed to compare the results
      between the different subtypes. A Bonferroni correction was applied to correct
      for multiple testing (alpha < .0033). RESULTS: MR imaging signs of diffuse
      intratumoral fat deposition were present in seven (78%) of nine liver-fatty acid
      binding protein (L-FABP)-negative HCAs compared with five (17%) of 29
      inflammatory HCAs (P = .001). Steatosis within the nontumoral liver was present
      in 11 (38%) of 29 inflammatory HCAs compared with none of the L-FABP-negative
      HCAs (P = .038). A characteristic atoll sign was only seen in the inflammatory
      group (P = .027). Presence of a typical vaguely defined type of scar was seen in
      five (71%) of seven beta-catenin-positive HCAs (P = .003). No specific MR imaging
      features were identified for the unclassified cases. CONCLUSION: L-FABP-negative,
      inflammatory, and beta-catenin-positive HCAs were related to MR imaging signs of
      diffuse intratumoral fat deposition, an atoll sign, and a typical vaguely defined
      scar, respectively. Since beta-catenin-positive HCAs are considered premalignant,
      closer follow-up with MR imaging or resection may be preferred.

PMID- 21875846
TI  - Gender differences in quality of life among long-term colorectal cancer survivors
      with ostomies.
AB  - PURPOSE/OBJECTIVES: To describe how gender shapes the concerns and adaptations of
      long-term (i.e., more than five years) colorectal cancer survivors with ostomies.
      DESIGN: Qualitative study using content analysis of focus group content. SETTING:
      Oregon, southwestern Washington, and northern California. SAMPLE: Four female and
      four male focus groups (N = 33) selected from 282 quantitative survey
      participants with health-related quality-of-life (HRQOL) scores in the highest or
      lowest quartile. METHODS: Eight focus groups discussed the challenges of living
      with an ostomy. Content was recorded, transcribed, and analyzed using directive
      and summative content analysis. MAIN RESEARCH VARIABLES: HRQOL domains of
      physical, psychological, social, and spiritual well-being. FINDINGS: All groups
      reported avoiding foods that cause gas or rapid transit and discussed how
      limiting the amount of food eaten controlled the output. All groups discussed
      physical activities, getting support from friends and family, and the importance
      of being resilient. Both genders identified challenges with sexuality and
      intimacy. Coping and adjustment difficulties mostly were discussed by women, with
      men only discussing these issues to a small extent. Difficulties with sleep
      primarily were identified by women with low HRQOL. Problems with body image and
      depression were discussed only by women with low HRQOL. CONCLUSIONS: Common
      issues included diet management, physical activity, social support, and
      sexuality. Although both genders identified challenges, women described more
      specific psychological and social issues than men. IMPLICATIONS FOR NURSING:
      Application of these gender-based differences can inform educational
      interventions for colorectal cancer survivors with ostomies.

PMID- 21875849
TI  - An evaluation of the use of smartphones to communicate between clinicians: a
      mixed-methods study.
AB  - BACKGROUND: Communication between clinicians is critical to providing quality
      patient care but is often hampered by limitations of current systems. Smartphones
      such as BlackBerrys may improve communication, but studies of these technologies
      have been limited to date. OBJECTIVE: Our objectives were to describe how
      smartphones were adopted for clinical communication within general internal
      medical wards and determine their impact on team effectiveness and communication.
      METHODS: This was a mixed-methods study that gathered data from the frequency of
      smartphone calls and email messages, clinicians' interviews, and ethnographic
      observations of clinical communication interactions. Triangulation of qualitative
      and quantitative data was undertaken to develop common themes that encompass
      comprehensive and representative insights across different methods. RESULTS:
      Findings from our study indicated that over a 24-hour period, nurses sent on
      average 22.3 emails to the physicians mostly through the "team smartphone," the
      designated primary point of contact for a specific medical team. Physicians
      carrying the team smartphone received on average 21.9 emails and 6.4 telephone
      calls while sending out 6.9 emails and initiating 8.3 telephone calls over the 24
      hour period. Our analyses identified both positive and negative outcomes
      associated with the use of smartphones for clinical communication. There was a
      perceived improvement in efficiency over the use of pagers for clinical
      communication for physicians, nurses, and allied health professionals. In
      particular, residents found that the use of smartphones helped to increase their
      mobility and multitasking abilities. Negative outcomes included frequent
      interruptions and discordance between what doctors and nurses considered urgent.
      Nurses perceived a worsening of the interprofessional relationships due to
      overreliance on messaging by text with a resulting decrease in verbal
      communication. Unprofessional behaviors were observed in the use of smartphones
      by residents. CONCLUSIONS: Routine adoption of smartphones by residents appeared
      to improve efficiency over the use of pagers for physicians, nurses, and allied
      health professionals. This was balanced by negative communication issues of
      increased interruptions, a gap in perceived urgency, weakened interprofessional
      relationships, and unprofessional behavior. Further communication interventions
      are required that balance efficiency and interruptions while maintaining or even
      improving interprofessional relationships and professionalism.

PMID- 21875851
TI  - Hepatic arterial injuries in 3110 patients following percutaneous transhepatic
      biliary drainage.
AB  - PURPOSE: To evaluate the frequency of hepatic arterial injury in 3110 patients
      who had undergone percutaneous transhepatic biliary drainage (PTBD) and assess
      the risk factors for hepatic arterial injury and the treatment outcome after
      transcatheter arterial embolization. MATERIALS AND METHODS: A total of 3110
      patients who underwent 3780 PTBDs between January 2003 and December 2008 were
      retrospectively assessed. This study was approved by the Institutional Review
      Board. The incidence of hepatic arterial injury was determined and the risk
      factors associated with it were analyzed by using univariate and multiple
      logistic regression analyses. Hepatic angiography was performed to identify the
      bleeding focus, followed by transcatheter arterial embolization. RESULTS: Hepatic
      arterial injuries occurred after 72 (1.9%) of 3780 PTBDs. When adjusted for
      benign disease, perihepatic ascites, platelet count of 50,000/mm(3) or less,
      international normalization ratio of 1.5 or greater, and left-sided puncture,
      multiple logistic regression analysis showed that left-sided PTBD (odds ratio,
      2.017; 95% confidence interval: 1.257, 3.236; P = .004) was the only independent
      risk factor associated with hepatic arterial injury. The technical and clinical
      success rates of transcatheter arterial embolization were 100% and 95.8%,
      respectively. Minor complications were observed in 58 (80.6%) patients, 55
      (76.4%) of whom had hepatic ischemia and three (4.2%) of whom had focal hepatic
      infarction. No major complication was observed in any patient. CONCLUSION:
      Hepatic arterial injury is a relatively rare complication of PTBD. Because left
      sided PTBD is the only independent risk factor associated with hepatic arterial
      injury, right-sided PTBD is preferable unless technical difficulty or secondary
      intervention necessitates left-sided PTBD. Moreover, transcatheter arterial
      embolization is a safe and effective method for treating hepatic arterial injury
      following PTBD.

PMID- 21875852
TI  - Effect of metabolic syndrome on coronary artery stenosis and plaque
      characteristics as assessed with 64-detector row cardiac CT.
AB  - PURPOSE: To investigate the prevalence and severity of subclinical coronary
      atherosclerosis and plaque characteristics in asymptomatic subjects according to
      the presence or absence of metabolic syndrome (MS) with multidetector computed
      tomography (CT). MATERIALS AND METHODS: This study was approved and the
      requirement for informed patient consent was waived by the local institutional
      review board. Degree of coronary artery stenosis, multivessel involvement, and
      plaque characteristics, as well as coronary artery calcium score (CACS), were
      assessed with 64-detector row CT in 3000 age- and sex-matched asymptomatic
      individuals (mean age, 50.2 years +/- 8.9 [standard deviation]; age range, 30-79
      years). Anthropometric and metabolic profiles were also measured. Multivariate
      logistic regression analyses were performed to identify variables related to
      coronary atherosclerosis and plaque types. RESULTS: Subjects with MS had
      significant coronary artery stenosis (>50% stenosis), multivessel involvement,
      more positive remodeling, more atherosclerotic coronary segments, and higher CACS
      than subjects without MS (P < .01 for all). Mixed and noncalcified plaques were
      also more prominent in subjects with MS than in those without MS (14.2% +/- 4.4
      vs 7.6% +/- 3.1 and 13.1% +/- 4.3 vs 7.3% +/- 2.8, respectively; P < .01 for
      both). After adjustment for confounding factors, MS was strongly associated with
      significant coronary artery stenosis, multivessel involvement, and mixed plaque.
      CONCLUSION: Multidetector CT is useful in the early diagnosis and evaluation of
      subclinical coronary atherosclerosis in asymptomatic patients with MS; however,
      future prospective studies are needed to address the clinical implications of
      these findings.

PMID- 21875853
TI  - Noninvasive evaluation of coronary distensibility in older adults: a feasibility
      study with MR angiography.
AB  - PURPOSE: To assess the feasibility of using magnetic resonance (MR) angiography
      to noninvasively measure the coronary distensibility index (CDI) in older adults.
      MATERIALS AND METHODS: This study was approved by the institutional review board
      and was compliant with HIPAA. Informed consent was obtained from all
      participants. Three-dimensional MR angiography was performed in 23 patients with
      type 2 diabetes mellitus (DM) (mean age, 72.9 years +/- 5.8 [standard deviation];
      age range, 65-84 years; 12 men, 11 women) and 50 healthy aging control subjects
      (mean age, 73.1 years +/- 5.6; age range, 64-84 years; 28 men, 22 women). Imaging
      data were acquired in the rest periods of cardiac motion identified during end
      systole and middiastole. For imaging data with different acquisition windows,
      cross-sectional coronary planes were reconstructed and matched for the same
      anatomy according to coronary landmarks. The CDI, defined as [(lumen area at
      systole--lumen area at diastole)/(lumen area at diastole * pulse pressure)] *
      1000, was compared between patients with DM and control subjects by using the
      Student t test. With the same protocol, CDIs were calculated in 10 randomly
      selected subjects by two independent readers. In addition, MR angiography (in
      systole and diastole) was repeated in those 10 subjects after repositioning.
      RESULTS: CDIs were measured in 43 coronary segments of patients with DM and in
      124 coronary segments of control subjects. The mean CDI in patients with DM was
      significantly lower than that in control subjects (2.79 mm Hg(-1) +/- 2.12 vs
      9.14 mm Hg(-1) +/- 5.87, respectively; P < .001). CDI measurements showed good
      intraobserver (r = 0.914), interobserver (r = 0.820), and imaging-repeat imaging
      agreements (r = 0.811). CONCLUSION: Coronary MR angiography is a reproducible and
      repeatable noninvasive method for detecting significant differences in coronary
      distensibility between patients with DM and healthy aging control subjects.

PMID- 21875854
TI  - Regional homogeneity changes in heroin-dependent individuals: resting-state
      functional MR imaging study.
AB  - PURPOSE: To identify heroin-related modulations of neural activity in the resting
      state in heroin-dependent individuals (HDIs) by using resting-state functional
      magnetic resonance (MR) imaging and a regional homogeneity method and to
      investigate whether these changes of neural activity can be related to duration
      of heroin use and to decision-making deficits in HDIs. MATERIALS AND METHODS:
      This prospective study was approved by the appropriate ethics committee, and
      written informed consent was obtained from each participant. Thirty-one HDIs
      receiving methadone-maintained treatment and 24 control subjects participated.
      Resting-state functional MR imaging was performed by using a gradient-echo echo
      planar imaging sequence. Regional homogeneity was calculated by using software.
      Voxel-based analysis of the regional homogeneity maps between control and HDI
      groups was performed with two-sample t tests by using software. Statistical maps
      were set at P less than .05 and were corrected for multiple comparisons. The Iowa
      gambling task (IGT) was used to assess participant decision making during
      uncertainty. Abnormal clusters revealed by group comparison were extracted and
      correlated with behavioral performance at the IGT and with duration of heroin
      use. RESULTS: Regional homogeneity was diminished in the bilateral medial
      orbitofrontal cortex (OFC), bilateral dorsal medial thalamus, bilateral cuneus,
      and lingual gyrus in HDIs compared with control subjects. There were negative
      correlations between mean regional homogeneity in the medial OFC, bilateral
      cuneus, and lingual gyrus and duration of heroin use. There was a positive
      correlation between mean regional homogeneity in the medial OFC and performance
      level at the IGT. CONCLUSION: The present study reveals resting-state
      abnormalities in HDIs that may lead to further improvement of the understanding
      of the neural substrates of cognitive impairment in HDIs.

PMID- 21875855
TI  - Clopidogrel discontinuation after acute coronary syndromes: frequency, predictors
      and associations with death and myocardial infarction--a hospital registry
      primary care linked cohort (MINAP-GPRD).
AB  - AIMS: Adherence to evidence-based treatments and its consequences after acute
      myocardial infarction (MI) are poorly defined. We examined the extent to which
      clopidogrel treatment initiated in hospital is continued in primary care; the
      factors predictive of clopidogrel discontinuation and the hazard of death or
      recurrent MI. METHODS AND RESULTS: We linked the Myocardial Ischaemia National
      Audit Project registry and the General Practice Research Database to examine
      adherence to clopidogrel in primary care among patients discharged from hospital
      after MI (2003-2009). Hospital Episode Statistics and national mortality data
      were linked, documenting all-cause mortality and non-fatal MI. Of the 7543 linked
      patients, 4650 were prescribed clopidogrel in primary care within 3 months of
      discharge. The adjusted odds of still being prescribed clopidogrel at 12 months
      were similar following non-ST-elevation myocardial infarction (NSTEMI) 53% (95%
      CI, 51-55) and ST-elevation myocardial infarction (STEMI) 54% (95% CI, 52-56),
      but contrast with statins: NSTEMI 84% (95% CI, 82-85) and STEMI 89% (95% CI, 87
      90). Discontinuation within 12 months was more frequent in older patients [>80
      vs. 40-49 years, adjusted hazard ratio (HR) 1.50 (95% CI, 1.15-1.94)] and with
      bleeding events [HR 1.34 (95% CI, 1.03-1.73)]. 18.15 patients per 100 person
      years (95% CI, 16.83-19.58) died or experienced non-fatal MI in the first year
      following discharge. In patients who discontinued clopidogrel within 12 months,
      the adjusted HR for death or non-fatal MI was 1.45 (95% CI, 1.22-1.73) compared
      with untreated patients, and 2.62 (95% CI, 2.17-3.17) compared with patients
      persisting with clopidogrel treatment. CONCLUSION: This is the first study to use
      linked registries to determine persistence of clopidogrel treatment after MI in
      primary care. It demonstrates that discontinuation is common and associated with
      adverse outcomes.

PMID- 21875856
TI  - Myocardial infarction and other co-morbidities in patients with chronic
      obstructive pulmonary disease: a Danish nationwide study of 7.4 million
      individuals.
AB  - AIMS: Myocardial infarction is nominally the most important co-morbidity in
      patients with chronic obstructive pulmonary disease, and the one with the
      greatest potential for treatment and prevention to improve the overall prognosis
      of chronic obstructive pulmonary disease patients. We assessed the extent of
      myocardial infarction and other co-morbidities in individuals with chronic
      obstructive pulmonary disease in the general population. METHODS AND RESULTS: We
      used individual participant data for the entire Danish population from 1980
      through 2006, comprising 140 million person-years of follow-up. We used
      information from four national Danish registries with 100% follow-up and detected
      ever-diagnosed chronic obstructive pulmonary disease (n = 313,958) and incident
      cases of a first myocardial infarction (n = 422,344), lung cancer (n = 116,629),
      hip fracture (n = 53,756), depression (n = 93 038), and diabetes mellitus (n =
      292 228). Multivariate adjusted hazard ratios for life-time association with ever
      diagnosed chronic obstructive pulmonary disease were 1.26 (95% CI 1.25-1.27) for
      myocardial infarction, 2.05 (2.03-2.08) for lung cancer, 2.12 (2.07-2.17) for hip
      fracture, 1.74 (1.70-1.77) for depression, and 1.21 (1.20-1.23) for diabetes
      mellitus, compared with controls; these risk estimates were highest in women and
      the youngest age groups. Before the first hospitalization with chronic
      obstructive pulmonary disease, multivariate adjusted odds ratios were 1.47 (1.44
      1.49) for myocardial infarction, 3.68 (3.52-3.84) for lung cancer, 1.16 (1.13
      1.18) for hip fracture, 1.88 (1.80-1.96) for depression, and 1.16 (1.13-1.18) for
      diabetes mellitus, compared with matched controls. Corresponding values after a
      chronic obstructive pulmonary disease hospitalization were 0.74 (0.73-0.76), 1.48
      (1.45-1.51), 1.23 (1.20-1.27), 1.21 (1.18-1.24), and 0.83 (0.81-0.85),
      respectively. CONCLUSION: Chronic obstructive pulmonary disease was associated
      with higher rates of myocardial infarction, lung cancer, diabetes, hip fracture,
      and depression, but the strength of these associations was modified after a first
      admission for chronic obstructive pulmonary disease. These associations may be
      related to common genetic and/or lifestyle/environmental risk factors, and
      therefore these factors are likely to have an adverse health impact rather than
      chronic obstructive pulmonary disease per se.

PMID- 21875857
TI  - Left ventricular remodelling in systolic heart failure using ivabradine. Slower
      is smaller is better?

PMID- 21875858
TI  - Effects of selective heart rate reduction with ivabradine on left ventricular
      remodelling and function: results from the SHIFT echocardiography substudy.
AB  - AIMS: The SHIFT echocardiographic substudy evaluated the effects of ivabradine on
      left ventricular (LV) remodelling in heart failure (HF). METHODS AND RESULTS:
      Eligible patients had chronic HF and systolic dysfunction [LV ejection fraction
      (LVEF) <=35%], were in sinus rhythm, and had resting heart rate >=70 bpm.
      Patients were randomly allocated to ivabradine or placebo, superimposed on
      background therapy for HF. Complete echocardiographic data at baseline and 8
      months were available for 411 patients (ivabradine 208, placebo 203). Treatment
      with ivabradine reduced LVESVI (primary substudy endpoint) vs. placebo [-7.0 +/-
      16.3 vs. -0.9 +/- 17.1 mL/m(2); difference (SE), -5.8 (1.6), 95% CI -8.8 to -2.7,
      P< 0.001]. The reduction in LVESVI was independent of beta-blocker use, HF
      aetiology, and baseline LVEF. Ivabradine also improved LV end-diastolic volume
      index (-7.9 +/- 18.9 vs. -1.8 +/- 19.0 mL/m(2), P= 0.002) and LVEF (+2.4 +/- 7.7
      vs. -0.1 +/- 8.0%, P< 0.001). The incidence of the SHIFT primary composite
      outcome (cardiovascular mortality or hospitalization for worsening HF) was higher
      in patients with LVESVI above the median (59 mL/m2) at baseline (HR 1.62, 95% CI
      1.03-2.56, P= 0.04). Patients with the largest relative reductions in LVESVI had
      the lowest event rates. CONCLUSION: Ivabradine reverses cardiac remodelling in
      patients with HF and LV systolic dysfunction.

PMID- 21875859
TI  - Heart rate reduction with ivabradine and health related quality of life in
      patients with chronic heart failure: results from the SHIFT study.
AB  - AIMS: Heart failure (HF) has a major impact on health-related quality of life
      (HQoL). The aim was to evaluate whether heart rate (HR) reduction with ivabradine
      can translate into increased HQoL in parallel to a reduction of primary outcomes
      in SHIFT. METHODS AND RESULTS: In symptomatic patients with systolic HF treated
      with recommended background therapy, HQoL was assessed by Kansas City
      Cardiomyopathy Questionnaire (KCCQ) containing the following dimensions: overall
      summary score (OSS) and clinical summary score (CSS), analysed at baseline, and
      4, 12, and 24 months, and last post-baseline visit. A total of 1944 patients (968
      ivabradine, 976 placebo) were evaluated. At 12 months, incidence of clinical
      events (cardiovascular death or hospital admission for HF) was inversely
      associated with KCCQ scores. Ivabradine reduced HR by 10.1 bpm (placebo
      corrected, P < 0.001) and improved KCCQ by 1.8 for CSS and 2.4 for OSS (placebo
      corrected, P = 0.02 and P < 0.01, respectively); these changes were associated
      with the change in HR for both CSS (P < 0.001) and OSS (P < 0.001). The
      relationship was found in both allocation groups though the changes were more
      pronounced in the ivabradine group. Health-related quality of life at follow-up
      was better preserved in the ivabradine group compared with placebo; poorest
      outcomes were seen in the placebo group with lowest KCCQ scores (<50).
      CONCLUSION: In patients with systolic HF, low HQoL is associated with an
      increased rate of cardiovascular death or hospital admission for HF. Reduction in
      HR with ivabradine is associated with improved HQoL. The magnitude of HR
      reduction is related to the extent of improvement in HQoL.

PMID- 21875860
TI  - Biventricular pacing is superior to right ventricular pacing in bradycardia
      patients with preserved systolic function: 2-year results of the PACE trial.
AB  - AIMS: The Pacing to Avoid Cardiac Enlargement (PACE) trial is a prospective,
      double-blinded, randomized, multicentre study that reported the superiority of
      biventricular (BiV) pacing to right ventricular apical (RVA) pacing in the
      prevention of left ventricular (LV) adverse remodelling and deterioration of
      systolic function at 1 year. In the current analysis, we report the results at
      extended 2-year follow-up for changes in LV function and remodelling. METHODS AND
      RESULTS: Patients (n = 177) with bradycardia and preserved LV ejection fraction
      (EF >=45%) were randomized to receive RVA or BiV pacing. The co-primary endpoints
      were LVEF and LV end-systolic volume (LVESV). Eighty-one (92%) of 88 in the RVA
      pacing group and 82 (92%) of 89 patients in the BiV pacing group completed 2-year
      follow-up with a valid echocardiography. In the RVA pacing group, LVEF further
      decreased from the first to the second year, but it remained unchanged in the BiV
      pacing group, leading to a significant difference of 9.9 percentage points
      between groups at 2-year follow-up (P < 0.001). Similarly, LVESV continues to
      enlarge from the first to the second year in the RVA pacing group, leading to a
      difference of 13.0 mL (P < 0.001) between groups. Predefined subgroup analysis
      showed consistent results with the whole study population for both co-primary
      endpoints, which included patients with pre-existing LV diastolic dysfunction.
      Eighteen patients in the BiV pacing group (20.2%) and 55 in the RVA pacing group
      (62.5%) had a significant reduction of LVEF (of >=5%, P < 0.001). CONCLUSION:
      Left ventricular adverse remodelling and deterioration of systolic function
      continues at the second year after RVA pacing. This deterioration is prevented by
      BiV pacing.

PMID- 21875861
TI  - Chronic right ventricular pacing, adverse remodelling, and CRT: an ounce of
      prevention?

PMID- 21875862
TI  - The relationship between ventricular electrical delay and left ventricular
      remodelling with cardiac resynchronization therapy.
AB  - AIMS: The aim of the present study was to evaluate the relationship between left
      ventricular (LV) electrical delay, as measured by the QLV interval, and outcomes
      in a prospectively designed substudy of the SMART-AV Trial. METHODS AND RESULTS:
      This was a multicentre study of patients with advanced heart failure undergoing
      cardiac resynchronization therapy (CRT) defibrillator implantation. In 426
      subjects, QLV was measured as the interval from the onset of the QRS from the
      surface ECG to the first large peak of the LV electrogram. Left ventricular
      volumes were measured by echocardiography at baseline and after 6 months of CRT
      by a blinded core laboratory. Quality of life (QOL) was assessed by a
      standardized questionnaire. When separated by quartiles based on QLV duration,
      reverse remodelling response rates (>15% reduction in LV end systolic volume)
      increased progressively from 38.7 to 68.4% and QOL response rate (>10 points
      reduction) increased from 50 to 72%. Patients in the highest quartile of QLV had
      a 3.21-fold increase (1.58-6.50, P = 0.001) in their odds of a reverse
      remodelling response after correcting for QRS duration, bundle branch block type,
      and clinical characteristics by multivariate logistic regression analysis.
      CONCLUSION: Electrical dyssynchrony, as measured by QLV, was strongly and
      independently associated with reverse remodelling and QOL with CRT. Acute
      measurements of QLV may be useful to guide LV lead placement.

PMID- 21875863
TI  - The time has come for clinical cardiovascular trials with plaque characterization
      as an endpoint.

PMID- 21875865
TI  - Older people's participation in and engagement with falls prevention
      interventions in community settings: an augment to the Cochrane systematic
      review.
AB  - BACKGROUND: Randomised controlled trials (RCTs) of fall prevention conducted in
      community settings have recently been systematically reviewed. OBJECTIVE: To
      augment this review by analysing older people's participation in the trials and
      engagement with the interventions. DESIGN: Review of the 99 single and
      multifactorial RCTs included in the Cochrane systematic review of falls
      prevention interventions. SETTING: Community. PARTICIPANTS: Adults aged 60+/mean
      age minus one standard deviation of 60+. METHODS: Calculated aggregate data on
      recruitment (proportion who accepted the invitation to participate), attrition at
      12 month follow-up (loss of participants), adherence (to intervention protocol)
      and whether adherence moderated the effect of interventions on trial outcomes.
      RESULTS: The median recruitment rate was 70.7% (64.2-81.7%, n = 78). At 12 months
      the median attrition rate including mortality was 10.9% (9.1-16.0%, n = 44).
      Adherence rates (n = 69) were >=80% for vitamin D/calcium supplementation; >=70%
      for walking and class-based exercise; 52% for individually targeted exercise;
      approximately 60-70% for fluid/nutrition therapy and interventions to increase
      knowledge; 58-59% for home modifications; but there was no improvement for
      medication review/withdrawal of certain drugs. Adherence to multifactorial
      interventions was generally >=75% but ranged 28-95% for individual components.
      The 13 studies that tested for whether adherence moderated treatment
      effectiveness produced mixed results. CONCLUSIONS: Using median rates for
      recruitment (70%), attrition (10%) and adherence (80%), we estimate that, at 12
      months, on average half of community-dwelling older people are likely to be
      adhering to falls prevention interventions in clinical trials.

PMID- 21875864
TI  - Dopamine cell transplantation in Parkinson's disease: challenge and perspective.
AB  - BACKGROUND: Functional imaging provides a valuable adjunct to clinical evaluation
      for assessing the efficacy of cell-based restorative therapies in Parkinson's
      disease (PD). SOURCES OF DATA: In this article, we review the latest advances on
      the use of positron emission tomography (PET) imaging in evaluating the surgical
      outcome of embryonic dopamine (DA) cell transplantation in PD patients. AREAS OF
      AGREEMENT: These studies suggest long-term cell survival and clinical benefit
      following striatal transplantation of fetal nigral tissue in PD patients and in
      models of experimental parkinsonism. AREAS OF CONTROVERSY: Adverse events
      subsequent to transplantation have also been noted and attributed to a variety of
      causes. GROWING POINTS: Optimal outcomes of DA cell transplantation therapies are
      dependent on tissue composition and phenotype of DA neurons in the graft. AREAS
      TIMELY FOR DEVELOPING RESEARCH: Given continued progress in DA neuron production
      from stem cells in recent years, transplantation of neural stem cells may be the
      next to enter clinical trials in patients. CONCLUSION: The existing data from
      studies of embryonic DA transplantation for advanced PD have provided valuable
      insights for the design of new cell-based therapies for the treatment of this and
      related neurodegenerative disorders.

PMID- 21875866
TI  - Transitioning between ambulatory EHRs: a study of practitioners' perspectives.
AB  - OBJECTIVE: To evaluate practitioners' expectations of, and satisfaction with,
      older and newer electronic health records (EHRs) after a transition. MATERIAL AND
      METHODS: Pre- and post-transition survey administered at six academic-affiliated
      ambulatory care practices from 2006 to 2008. Four practices transitioned to one
      commercial EHR and two practices to another. We compared respondents'
      expectations of, and satisfaction with, the newer EHR. RESULTS: 523 subjects were
      eligible: 217 were available before transition and 306 after transition. 162 pre
      transition and 197 post-transition responses were received, yielding 75% and 64%
      response rates, respectively. Practitioners were more satisfied with the newer
      EHRs (64%) compared with the older (56%) (p=0.15) and a small majority (58%) were
      satisfied with the transition. Practitioners' satisfaction with the older EHRs
      for completing clinical tasks was high. The newer EHRs exceeded practitioner
      expectations regarding remote access (61% vs 74%; p=0.03). However, the newer
      EHRs did not meet practitioners' expectations regarding their ability to perform
      clinical tasks, or more globally, improve medication safety (81% vs 61%;
      p<0.001), efficiency (70% vs 44%; p<0.001), and quality of care (77% vs 67%;
      p=0.04). DISCUSSION: Most practitioners had favorable opinions about EHRs and
      reported overall improved satisfaction with the newer EHRs. However,
      practitioners' high expectations of the newer EHRs were often unmet regarding
      facilitation of specific clinical tasks or for improving quality, safety, and
      efficiency. CONCLUSION: To ensure practitioners' expectations, for instance
      regarding improvements in medication safety, are met, vendors should develop and
      implement refinements in their software as practices upgrade to newer, certified
      EHRs.

PMID- 21875867
TI  - Predicting the outcome of renal transplantation.
AB  - OBJECTIVE: Renal transplantation has dramatically improved the survival rate of
      hemodialysis patients. However, with a growing proportion of marginal organs and
      improved immunosuppression, it is necessary to verify that the established
      allocation system, mostly based on human leukocyte antigen matching, still meets
      today's needs. The authors turn to machine-learning techniques to predict, from
      donor-recipient data, the estimated glomerular filtration rate (eGFR) of the
      recipient 1 year after transplantation. DESIGN: The patient's eGFR was predicted
      using donor-recipient characteristics available at the time of transplantation.
      Donors' data were obtained from Eurotransplant's database, while recipients'
      details were retrieved from Charite Campus Virchow-Klinikum's database. A total
      of 707 renal transplantations from cadaveric donors were included. MEASUREMENTS:
      Two separate datasets were created, taking features with <10% missing values for
      one and <50% missing values for the other. Four established regressors were run
      on both datasets, with and without feature selection. RESULTS: The authors
      obtained a Pearson correlation coefficient between predicted and real eGFR (COR)
      of 0.48. The best model for the dataset was a Gaussian support vector machine
      with recursive feature elimination on the more inclusive dataset. All results are
      available at http://transplant.molgen.mpg.de/. LIMITATIONS: For now, missing
      values in the data must be predicted and filled in. The performance is not as
      high as hoped, but the dataset seems to be the main cause. CONCLUSIONS:
      Predicting the outcome is possible with the dataset at hand (COR=0.48). Valuable
      features include age and creatinine levels of the donor, as well as sex and
      weight of the recipient.

PMID- 21875869
TI  - Declining incidence of breast cancer after decreased use of hormone-replacement
      therapy: magnitude and time lags in different countries.
AB  - Throughout the latter half of the 20th century, hormone-replacement therapy (HRT)
      use steadily increased in the Western world. In 2002, the early termination of
      the Women's Health Initiative trial due to an excess of adverse events
      attributable to HRT, led to a precipitous decline in its use. Breast cancer
      incidence began to decline soon thereafter in the USA and several other
      countries. However, the magnitude of the decline in breast cancer incidence, and
      its timing with respect to HRT cessation, shows considerable variability between
      nations. The impact of HRT cessation appears most significant and immediate in
      countries with the largest absolute decline in HRT use. In countries in which
      peak prevalence of HRT use was high, several studies have convincingly excluded
      decreasing rates of mammographic screening as an explanation for the decline in
      breast cancer incidence. Conversely, in some countries, no decline in breast
      cancer incidence is apparent that can be readily attributed to declining trends
      in HRT use. In such cases, declines in breast cancer incidence may be related
      instead to saturation or decreased utilisation of mammographic screening
      programmes. In other cases, it is difficult to disentangle the respective
      influence of trends in HRT use, and the influence of changes relating to
      mammographic screening. However, irrespective of time lags and varying magnitudes
      of effect, the data convincingly support a direct association between decreasing
      HRT use and declining breast cancer incidence.

PMID- 21875868
TI  - Identifying dietary patterns using a normal mixture model: application to the
      EPIC study.
AB  - BACKGROUND: Finite mixture models posit the existence of a latent categorical
      variable and can be used for probabilistic classification. The authors illustrate
      the use of mixture models for dietary pattern analysis. An advantage of this
      approach is taking classification uncertainty into account. METHODS: Participants
      were a random sample of women from the European Prospective Investigation into
      Cancer. Food consumption was measured using dietary questionnaires. Mixture
      models identified latent classes in food consumption data, which were interpreted
      as dietary patterns. RESULTS: Among various assumptions examined, models allowing
      the variance of foods to vary within and between classes fit better than
      alternatives assuming constant variance (the K-means method of cluster analysis
      also makes the latter assumption). An eight-class model was best fitting and five
      patterns validated well in a second random sample. Patterns with lower
      classification uncertainty tended to be better validated. One pattern showed low
      consumption of foods despite being associated with moderate body mass index.
      CONCLUSION: Mixture modelling for dietary pattern analysis has advantages over
      both factor and cluster analysis. In contrast to these other methods, it is easy
      to estimate pattern prevalence, to describe patterns and to use patterns to
      predict disease taking classification uncertainty into account. Owing to
      substantial error in food consumptions, any analysis will usually find some
      patterns that cannot be well validated. While knowledge of classification
      uncertainty may aid pattern evaluation, any method will better identify patterns
      from food consumptions measured with less error. Mixture models may be useful to
      identify individuals who under-report food consumption.

PMID- 21875870
TI  - Clinical profile of graft detachment and outcomes of rebubbling after Descemet
      stripping endothelial keratoplasty.
AB  - PURPOSE: To review the clinical profile of graft detachment following Descemet's
      stripping endothelial keratoplasty (DSEK) and analyse the outcomes of rebubbling
      for graft detachment. METHODS: Retrospective review. RESULTS: 27 of a total of
      309 eyes that underwent DSEK (8.7%) underwent rebubbling with air injection
      between January 2009 and February 2010. Eighteen (66.6%) of these eyes had
      complete and 9 (33.3%) had partial detachment of the transplanted lenticule.
      Successful attachment was observed in 20/27 (74%) eyes (12/18 with total and 8/9
      with partial detachments), and clear grafts were achieved in 13 (65%) of these 20
      eyes, while 7 (35%) eyes had primary graft failure. Visual acuity was 20/60 or
      better in 6 of these 20 eyes (35%), between 20/100 and 20/60 in 4 eyes (25%), and
      <20/200 in 10 eyes. Three of the 10 lenticules that failed to attach with the
      first rebubbling procedure underwent a second attempt of rebubbling, four
      underwent a repeat DSEK with good outcomes, and three underwent PK. Univariate
      analysis showed additional vitrectomy at the time of DSEK to be a statistically
      significant risk factor for persistent graft detachment following rebubbling
      (p<0.04). CONCLUSION: Rebubbling following detachment of the donor lenticule was
      successful in achieving graft adhesion in the majority of patients (74%), but 35%
      had a primary graft failure. The second attempt at rebubbling (in three patients)
      led to successful attachment, but the oedema failed to recover. Those who
      underwent repeat DSEK for unsuccessful rebubbling did well with no complications.

PMID- 21875871
TI  - Trends over time and geographical variation in rates of intravitreal injections
      in England.
AB  - AIMS: The recent emergence of antivascular endothelial growth factor (anti-VEGF)
      drugs has led to increased numbers of patients undergoing intravitreal injection
      for age-related macular degeneration (AMD). The aims of this study were to report
      on trends over time and geographical variation in intravitreal injection rates in
      England, and consider the implications for publicly funded health services of
      introducing new and expensive treatments. METHODS: Hospital episode statistics
      were analysed for annual treatment rates of intravitreal injection between the
      NHS financial years of 1989/1990 and 2008/1999. RESULTS: Annual injection rates
      increased from 0.4 episodes (95% CI 0.37 to 0.49) per 100,000 population in
      1989/1990 to 10.7 (10.4-11.0) in 2006/2007. Rates then rose exponentially to 59.5
      (58.8-60.2) in 2008/2009, with increasing use of multiple injections per person.
      The largest growth in injection rates was found in older people, and for AMD.
      Numbers of treatment episodes increased from 203 (1989/1990) to 30,458
      (2008/2009). Geographical analysis showed a very wide variation across local
      authority areas in injection rates, from 0.9 (0.2-2.2) to 42.2 (38.9-45.7) people
      per 100,000 population in 2005-2008. CONCLUSION: Rates of intravitreal injection
      increased exponentially from 2006/2007. This followed the US Food and Drug
      Association licensing of ranibizumab for the treatment of neovascular AMD (2006),
      and its recommendation by National Institute for Health and Clinical Excellence
      (2008). This study demonstrates some of the major issues which arise with the
      emergence of expensive new treatments, including speed and cost of adoption,
      geographical variation in access, and implications for licensing, commissioning
      and health financing in an ageing society.

PMID- 21875872
TI  - Interleukin-1 receptor-associated kinase-M suppresses systemic lupus
      erythematosus.
AB  - OBJECTIVES: Interleukin-1 receptor-associated kinase (IRAK)-M suppresses Toll
      like receptor (TLR)-mediated activation of innate immunity during infection. A
      similar role was hypothesised for IRAK-M in autoimmunity. METHODS: Irak-m
      deficient mice were crossed with autoimmune C57BL/6-lpr/lpr mice and detailed
      phenotype analysis was performed. RESULTS: Irak-m deficiency converted the mild
      autoimmune phenotype of C57BL/6-lpr/lpr mice into a massive lymphoproliferative
      syndrome with lethal autoimmune lung disease and lupus nephritis. Irak-m
      deficiency induced a number of interferon-related genes, cytokines and plasma
      cell survival factors in spleen cells of these mice. Irak-m-deficient C57BL/6
      lpr/lpr mice showed expansion of autoreactive T cells, dysfunctional regulatory T
      cells and plasma cells which was associated with increased lupus autoantibody
      production. TLR7 antagonism almost completely abrogated this phenotype consistent
      with IRAK-M-mediated suppression of TLR7 signalling in vitro. CONCLUSIONS: These
      data identify a previously unknown function of IRAK-M-namely, suppression of TLR7
      mediated autoimmunity-and mutant IRAK-M as a previously unknown genetic risk for
      murine SLE.

PMID- 21875873
TI  - Performance of the new 2011 ACR/EULAR remission criteria with tocilizumab using
      the phase IIIb study TAMARA as an example and their comparison with traditional
      remission criteria.
AB  - BACKGROUND: Remission is the established goal in rheumatoid arthritis (RA)
      treatment. Although originally defined by a disease activity score in 28 joints
      (DAS28) <2.6, more stringent criteria may imply the absence of disease activity.
      The 2011 ACR/EULAR remission criteria provide the newest and most stringent
      definition of remission. OBJECTIVES: To evaluate post hoc the remission by
      ACR/EULAR criteria and compare the criteria with the conventional DAS28 in
      TAMARA, an open-label phase IIIb tocilizumab (TCZ) trial including patients with
      active RA receiving inadequate disease-modifying antirheumatic drugs (DMARDs) or
      tumour necrosis factor alpha (TNFalpha) inhibitor treatment. RESULTS: 286
      patients were enrolled, 99.7% of patients were receiving a conventional DMARD and
      41.6% had TNFalpha inhibitor pretreatment. Baseline mean DAS28 of 6.0 +/- 1.0
      fell to 2.6 +/- 1.5 at week 24. DAS28 <2.6 was achieved by 47.6% at week 24.
      Remission rates with the new ACR/EULAR Boolean-based criteria for clinical
      studies were 15.0% after 12 weeks and 20.3% after 24 weeks. Of note, 13.5% of
      patients with previous TNFalpha blocker inadequate response still achieved
      remission according to the new ACR/EULAR criteria after 24 weeks. Clinical
      Disease Activity Index and Simplified Disease Activity Index remission rates were
      24.1% and 25.2%, respectively. CONCLUSIONS: Under the definition of the new
      stringent 2011 ACR/EULAR remission criteria, patients with active RA despite
      DMARD treatment and even after inadequate response to TNFalpha inhibitors,
      receiving TCZ showed significant rates of remission. Similar remission rates were
      achieved, when clinical practice criteria, not inclusive of acute phase
      reactants, were used.

PMID- 21875874
TI  - Treatment strategies in patients with rheumatoid arthritis for whom methotrexate
      monotherapy has failed: data from the NOR-DMARD register.
AB  - OBJECTIVES: To compare the effectiveness of adding synthetic disease-modifying
      antirheumatic drugs (sDMARDs) versus tumour necrosis factor alpha inhibitors
      (TNFi) to methotrexate (MTX) in patients with rheumatoid arthritis (RA) who were
      MTX inadequate responders (IR). Second, to examine outcomes in patients receiving
      MTX+TNFi for whom the MTX+sDMARD combination had also failed. METHODS: Patients
      with RA (disease duration <= 5 years, MTX IR and naive to other DMARDs) starting
      treatment with MTX+TNFi or MTX+sDMARDs were included. From the latter group a
      subgroup of patients who went on to receive MTX+TNFi was identified. RESULTS:
      Patients receiving MTX+TNFi (n=98) and MTX+sDMARDs (n=129) had similar baseline
      disease activity when starting combination therapy (mean Disease Activity Score
      28 (DAS28) = 4.90 and 4.96, respectively). Three- and 6-month effectiveness and 2
      year drug survival were better for MTX+TNFi than for MTX+sDMARDs: mean DAS28 was 
      1.61 versus -0.85 after 3 months (p<0.001) and -1.91 versus -1.03 after 6 months
      (p=0.01); DAS28<2.6 was reached by 29.0% versus 11.6% after 3 and 34.5% versus
      12.9% after 6 months. Effectiveness was somewhat better with triple therapy than
      other MTX+sDMARD combinations but was generally inferior compared with MTX+TNFi.
      For the patients who received MTX+TNFi as a third step after MTX+sDMARDs had
      failed (n=38) there was a tendency towards lower remission rates, worse disease
      activity states and inferior drug survival compared with patients who received
      MTX+TNFi directly after the failure of MTX. CONCLUSIONS: Effectiveness was better
      for MTX+TNFi than for MTX+sDMARDs. Patients who started MTX+TNFi after two
      synthetic DMARD regimens had failed had a tendency to less favourable disease
      states after 3 months than patients who switched directly from MTX to MTX+TNFi.

PMID- 21875875
TI  - The ecological validity of clinical tests of visuospatial function in community
      dwelling older adults.
AB  - Little is known about the relation between measures of visuospatial function and
      daily functioning in community-dwelling older adults. The current study addresses
      this gap in the literature. Forty individuals with mean (SD) age and education of
      78.4 (7.5) and 11.9 (2.6) years, respectively, completed a battery of
      neuropsychological measures including traditional tests of visuospatial function,
      a test of visuospatial function with verisimilitude, and performance-based
      measures of global daily functioning and visuospatial daily functioning. Unlike
      previous studies, statistical analyses directly evaluated the magnitude of the
      correlations between cognitive tests and daily functioning. Results indicated
      that all visuospatial measures significantly correlated with both measures of
      daily functioning (rs = .34-.59). Although the measure designed with
      verisimilitude was not significantly better than the traditional visuospatial
      measures at predicting daily functioning, it did account for significant variance
      beyond that accounted for by the other tests, supporting its incremental
      validity.

PMID- 21875876
TI  - The contribution of disease activity on functional limitations over time through
      psychological mediators: a 12-month longitudinal study in patients with
      ankylosing spondylitis.
AB  - OBJECTIVES: To explore whether helplessness, internality and depression would
      mediate the relationship between disease activity and functional limitations in
      patients with AS in a 12-month longitudinal study. METHODS: A total of 294
      participants with AS meeting modified New York criteria completed clinical and
      psychological assessments at 6-month intervals. Psychological measures evaluated
      helplessness, depression and internality. Path analysis evaluated the direct and
      indirect effects of baseline disease activity on 12-month functional limitations
      via the psychological measures of helplessness, internality and depression at 6
      months. RESULTS: Baseline disease activity demonstrated direct and indirect
      effects on 12-month functional limitations. Helplessness and depression, but not
      internality, served as mediators of the relationship between disease activity and
      functional limitations. CONCLUSION: Higher baseline disease activity predicted
      greater functional limitations at 12 months through helplessness and depression.
      Our findings suggest that helplessness and depression may constitute future
      treatment targets in reducing functional limitations in patients with AS.

PMID- 21875877
TI  - Clinical and ultrasonography assessment of peripheral enthesitis in ankylosing
      spondylitis.
AB  - OBJECTIVE: The aim of this study was to compare clinical examination with power
      Doppler US (PDUS) in the detection of entheseal abnormalities in patients with
      AS. METHODS: Thirty-six AS patients underwent clinical and PDUS examination of
      the following bilateral entheseal sites: common extensor tendon at its insertion
      at the lateral humeral epicondyle; gluteus tendons at their insertion at the
      greater trochanter; quadriceps tendon at its insertion at the superior pole of
      the patella; patellar tendon at its proximal insertion at the inferior pole of
      the patella; patellar tendon at its distal insertion at the tibial tuberosity;
      Achilles tendon at its insertion at the calcaneus; and plantar aponeuroses at its
      insertion at the calcaneus. RESULTS: Clinical and PDUS examination revealed at
      least one abnormal enthesis in 23 (63.9%) and 35 (97.2%) AS patients,
      respectively. Furthermore, of 432 entheses examined in our 36 AS patients, 64
      (14.8%) were considered abnormal by clinical examination and 192 (44.4%) by PDUS.
      US abnormalities most commonly found were enthesophytes (31.7%), calcifications
      (33.7%), thickening (29.8%) and hypoechogenicity (26.6%). We found erosions and
      PD signals in 9.7 and 6% of examined entheseal sites, respectively. The evidence
      of entheseal abnormalities by clinical examination has a poor likelihood ratio
      (LR) for the presence of US abnormalities with vascularization (LR = 1.61),
      without vascularization (LR = 1.24) or erosions (LR = 1.51) at all sites.
      CONCLUSIONS: PDUS permits detection of structural and inflammatory abnormalities
      of the enthesis in AS and may complement the physical examination in order to
      better evaluate enthesitis.

PMID- 21875878
TI  - Lumbar canal spinal stenosis due to axial skeletal calcinosis and heterotopic
      ossification in limited cutaneous systemic sclerosis: successful spinal
      decompression.

PMID- 21875879
TI  - Fatigue in RA.

PMID- 21875880
TI  - Predictors of progression in atherosclerosis over 2 years in systemic lupus
      erythematosus.
AB  - OBJECTIVES: Cardiovascular disease remains the major cause of death in SLE. We
      assessed the degree to which cardiovascular risk factors (CVRFs) and disease
      activity were associated with 2-year changes in measures of subclinical
      atherosclerosis. METHODS: One hundred and eighty-seven SLE patients participating
      in a placebo-controlled trial of atorvastatin underwent multi-detector CT [for
      coronary artery calcium (CAC)] and carotid duplex [for carotid intima-media
      thickness (IMT) and carotid plaque] twice, 2 years apart. During the 2 years,
      patients were assessed every 3 months for CVRF. Both groups were combined for
      analysis, as atorvastatin did not differ from placebo in preventing progression
      of coronary calcium. We examined the correlation between these clinical measures
      and progression of CAC, IMT and plaque during the follow-up period. RESULTS: In
      an analysis adjusting for age, gender and ethnicity, CAC progression was
      positively associated with total serum cholesterol measured over the 2-year
      period (P = 0.04) and smoking (P = 0.003). Carotid IMT progression was associated
      with systolic BP (P = 0.003), high-sensitivity CRP (hsCRP) (P = 0.013) and white
      blood cell (WBC) count (P = 0.029). Carotid plaque progression, defined as
      patients without carotid plaque at baseline with subsequent development of plaque
      at follow-up, was associated with systolic BP (P = 0.003), WBC count (P = 0.02),
      physician's global assessment (P = 0.05), blood lymphocyte count (P = 0.048),
      urine protein (P = 0.017) and duration of SLE (P = 0.019). CONCLUSION: Our data
      did not provide evidence of an association between measures of SLE disease
      activity (SLEDAI, anti-dsDNA, anti-phospholipid and treatment) and progression of
      subclinical atherosclerosis. Age and hypertension were associated with the
      progression of carotid IMT and plaque. Age, smoking and cholesterol were
      associated with progression of CAC.

PMID- 21875881
TI  - Paediatric rheumatology in India: challenges and opportunities.

PMID- 21875882
TI  - TBK1: a potential therapeutic target in RA.

PMID- 21875883
TI  - Confirmation of association of the macrophage migration inhibitory factor gene
      with systemic sclerosis in a large European population.
AB  - OBJECTIVES: The aim of this study was to confirm the implication of macrophage
      migration inhibitory factor (MIF) gene in SSc susceptibility or clinical
      phenotypes in a large European population. METHODS: A total of 3800 SSc patients
      and 4282 healthy controls of white Caucasian ancestry from eight different
      European countries were included in the study. The MIF -173 single nucleotide
      polymorphism (SNP) was selected as genetic marker and genotyped using Taqman 5'
      allelic discrimination assay. RESULTS: The MIF -173 SNP showed association with
      SSc [P = 0.04, odds ratio (OR) = 1.10, 95% CI 1.00, 1.19]. Analysis of the MIF 
      173 polymorphism according to SSc clinical phenotype revealed that the frequency
      of the -173*C allele was significantly higher in the dcSSc group compared with
      controls (P = 5.30E-03, OR = 1.21, 95% CI 1.07, 1.38). Conversely, the frequency
      of the MIF -173*C allele was significantly underrepresented in the lcSSc group
      compared with dcSSc patients, supporting previous findings [(P = 0.04, OR = 0.86,
      95% CI 0.75, 0.99); meta-analysis including previous results (P = 0.005, OR =
      0.83, 95% CI 0.73, 0.94)]. CONCLUSION: Our results confirm the role of MIF -173
      promoter polymorphism in SSc, and provide evidence of a strong association with
      the dcSSc subgroup of patients. Hence, the MIF -173 variant is confirmed as a
      promising clinical phenotype genetic marker.

PMID- 21875884
TI  - The fine specificity of mannose-binding and galactose-binding lectins revealed
      using outlier motif analysis of glycan array data.
AB  - Glycan-binding proteins are commonly used as analytical reagents to detect the
      levels of specific glycan structures in biological samples. A detailed knowledge
      of the specificities of glycan-binding proteins is required for properly
      interpreting their binding data. A powerful technology for characterizing glycan
      binding specificity is the glycan array. However, the interpretation of glycan
      array data can be difficult due to the complex fine specificities of certain
      glycan-binding proteins. We developed a systematic approach, called outlier-motif
      analysis, for extracting fine-specificity information from glycan-array data, and
      we applied the method to the study of four commonly used lectins: two mannose
      binders (concanavalin A and Lens culinaris) and two galactose binders (Bauhinia
      purpurea and peanut agglutinin). The study confirmed the known, primary
      specificity of each lectin and also revealed new insights into their binding
      preferences. Lens culinaris's main specificity may be non-terminal, alpha-linked
      mannose with a single linkage at its 2' carbon, which is more restricted than
      previous definitions. We found broader specificity for bauhinea purpurea (BPL)
      than previously reported, showing that BPL can bind terminal N
      acetylgalactosamine (GalNAc) and penultimate beta-linked galactose under certain
      limitations. Peanut agglutinin may bind terminal Galbeta1,3Gal, a glycolipid
      motif, in addition to terminal Galbeta1,3GalNAc, a common O-linked glycoprotein
      motif. These results could be used to more accurately interpret data obtained
      using these well-studied lectins. Furthermore, this study demonstrates a
      systematic and general approach for extracting fine-specificity information from
      glycan-array data.

PMID- 21875886
TI  - Transesophageal echocardiography-guided aortic thrombectomy in a patient with a
      mobile thoracic aortic thrombus.
AB  - Thoracic aortic thrombi are a well-known cause of distal embolic phenomena. There
      is a paucity of case reports because of the rarity of this condition, and thus
      clear management guidelines are lacking. The authors present a case of a mobile
      thoracic aortic thrombus managed by a surgical approach. This report demonstrates
      how intraoperative transesophageal echocardiography (TEE) proved to be critical
      in guiding surgical management. The utility of TEE in the diagnosis and
      management of aortic thrombi is also discussed. In addition, currently reported
      management strategies for this complex condition are reviewed.

PMID- 21875887
TI  - Detection of left ventricular apical thrombus with three-dimensional
      transesophageal echocardiography.
AB  - OBJECTIVE. Left ventricular (LV) thrombosis persists as a clinical challenge in
      echocardiographic diagnosis and is an important risk factor for perioperative
      embolic events in cardiac surgery. Appropriate detection and monitoring when
      thrombus is suspected is critical in surgical planning and in avoiding
      catastrophic patient outcomes. CASE PRESENTATION. The authors present a case of a
      laminated LV apical thrombus, which was discovered intraoperatively by real-time
      3-dimensional (3D) transesophageal echocardiography. CLINICAL CHALLENGES. The
      clinical challenges were (a) LV thrombosis impact on surgical management, (b) key
      echocardiographic challenges in diagnosing LV thrombosis, and (c) role of 3D
      echocardiography in the diagnostic algorithm. CONCLUSION. Because of the lack of
      a gold standard, 2D transthoracic echocardiography remains the imaging modality
      of choice in assessment; however, there is increasing evidence that 3D technology
      can be more accurate in intracardiac mass detection and should be considered in
      the diagnostic algorithm.

PMID- 21875885
TI  - Chocolate consumption and cardiometabolic disorders: systematic review and meta
      analysis.
AB  - OBJECTIVE: To evaluate the association of chocolate consumption with the risk of
      developing cardiometabolic disorders. DESIGN: Systematic review and meta-analysis
      of randomised controlled trials and observational studies. DATA SOURCES: Medline,
      Embase, Cochrane Library, PubMed, CINAHL, IPA, Web of Science, Scopus, Pascal,
      reference lists of relevant studies to October 2010, and email contact with
      authors. STUDY SELECTION: Randomised trials and cohort, case-control, and cross
      sectional studies carried out in human adults, in which the association between
      chocolate consumption and the risk of outcomes related to cardiometabolic
      disorders were reported. DATA EXTRACTION: Data were extracted by two independent
      investigators, and a consensus was reached with the involvement of a third. The
      primary outcome was cardiometabolic disorders, including cardiovascular disease
      (coronary heart disease and stroke), diabetes, and metabolic syndrome. A meta
      analysis assessed the risk of developing cardiometabolic disorders by comparing
      the highest and lowest level of chocolate consumption. RESULTS: From 4576
      references seven studies met the inclusion criteria (including 114,009
      participants). None of the studies was a randomised trial, six were cohort
      studies, and one a cross sectional study. Large variation was observed between
      these seven studies for measurement of chocolate consumption, methods, and
      outcomes evaluated. Five of the seven studies reported a beneficial association
      between higher levels of chocolate consumption and the risk of cardiometabolic
      disorders. The highest levels of chocolate consumption were associated with a 37%
      reduction in cardiovascular disease (relative risk 0.63 (95% confidence interval
      0.44 to 0.90)) and a 29% reduction in stroke compared with the lowest levels.
      CONCLUSIONS: Based on observational evidence, levels of chocolate consumption
      seem to be associated with a substantial reduction in the risk of cardiometabolic
      disorders. Further experimental studies are required to confirm a potentially
      beneficial effect of chocolate consumption.

PMID- 21875888
TI  - Early degeneration of a bioprosthetic mitral valve complicated by a large left
      atrial thrombus.
AB  - The authors report the case of a patient with symptomatic early bioprosthetic
      mitral valve deterioration in the setting of calcium supplementation. This was
      further complicated by a large left atrial thrombus despite supratherapeutic
      anticoagulation and a previously oversewn left atrial appendage. As mechanical
      valves are less predisposed to calcification in comparison with bioprosthetic
      implants, the patient underwent a mechanical mitral valve replacement in addition
      to a left atrial thrombectomy.

PMID- 21875889
TI  - Roy's adaptation model. Interview by Pamela Clarke.
AB  - This column presents a dialogue with three Roy scholars. They discuss research,
      practice, administration, and education issues in nursing from a Roy perspective
      and present data on curriculum in schools across the United States in relation to
      the use of nursing theory and Roy's model.

PMID- 21875890
TI  - Time course of cortical plasticity after facial nerve palsy: a single-case study.
AB  - BACKGROUND: Functional connectivity is defined as the temporal correlation
      between spatially remote neurophysiological events. This method has become
      particularly useful for studying neuroplasticity to detect changes in the
      collaboration of brain areas during cortical reorganization. METHODS: In this
      article, the authors longitudinally studied voxel-based morphometry and resting
      state functional magnetic resonance imaging 10 times in 1 patient during the
      course of Bell palsy (idiopathic facial nerve palsy) up to complete clinical
      recovery. RESULTS: Morphometric analysis revealed a significant alteration in the
      face area of the primary motor cortex (M1) contralateral to the paretic face,
      with an initial increase in gray matter concentration. Functional connectivity
      analysis between the M1 and other parts of the facial motor network revealed
      acutely disrupted intrahemispheric connectivity but unaltered interhemispheric
      connectivity. The disrupted functional connectivity was most pronounced on the
      day of the onset of symptoms, with a subsequent return toward normal during the
      course of recovery. This time course was found to differ between the selected
      parts of the facial motor network. However, the increase in functional
      connectivity strength preceded clinical recovery in all areas and reached a
      stable level before the patient fully recovered. CONCLUSION: These results
      demonstrate that recovery from facial nerve palsy is complemented by cortical
      reorganization, with pronounced changes of functional connectivity that precede
      clinical recovery.

PMID- 21875891
TI  - Magnetic grip facilitates feeding with weakened hands after spinal cord injury.

PMID- 21875892
TI  - Contralaterally controlled functional electrical stimulation for upper extremity
      hemiplegia: an early-phase randomized clinical trial in subacute stroke patients.
AB  - BACKGROUND: Contralaterally controlled functional electrical stimulation (CCFES)
      is an experimental treatment intended to improve hand function after stroke.
      OBJECTIVE: To compare the effects of 6 weeks of CCFES versus cyclic neuromuscular
      electrical stimulation (NMES) on upper extremity impairment and activity
      limitation in patients <=6 months poststroke. METHODS: Twenty-one participants
      were randomized to CCFES or cyclic NMES. Treatment for both groups consisted of
      daily stimulation-assisted repetitive hand-opening exercise at home plus twice
      weekly lab sessions of functional task practice. Assessments were made at
      pretreatment and posttreatment and at 1 month and 3 months posttreatment. They
      included maximum voluntary finger extension angle, finger movement tracking
      error, upper extremity Fugl-Meyer score, Box and Blocks test, and Arm Motor
      Abilities test. Treatment effects were estimated using a 2-factor repeated
      measures analysis of variance with the value of the baseline measure as a
      covariate. RESULTS: Seventeen patients completed the treatment phase (9 CCFES, 8
      cyclic NMES). At all posttreatment time points, CCFES produced larger
      improvements than cyclic NMES on every outcome measure. Maximum voluntary finger
      extension showed the largest treatment effect, with a mean group difference
      across the posttreatment time points of 28 degrees  more finger extension for
      CCFES. CONCLUSIONS: The results favor CCFES over cyclic NMES though the small
      sample size limits the statistical power of the study. The effect size estimates
      from this study will be used to power a larger trial.

PMID- 21875893
TI  - GeBP/GPL transcription factors regulate a subset of CPR5-dependent processes.
AB  - The CONSTITUTIVE EXPRESSOR OF PATHOGENESIS-RELATED GENES5 (CPR5) gene of
      Arabidopsis (Arabidopsis thaliana) encodes a putative membrane protein of unknown
      biochemical function and displays highly pleiotropic functions, particularly in
      pathogen responses, cell proliferation, cell expansion, and cell death. Here, we
      demonstrate a link between CPR5 and the GLABRA1 ENHANCER BINDING PROTEIN (GeBP)
      family of transcription factors. We investigated the primary role of the
      GeBP/GeBP-like (GPL) genes using transcriptomic analysis of the quadruple gebp
      gpl1,2,3 mutant and one overexpressing line that displays several cpr5-like
      phenotypes including dwarfism, spontaneous necrotic lesions, and increased
      pathogen resistance. We found that GeBP/GPLs regulate a set of genes that
      represents a subset of the CPR5 pathway. This subset includes genes involved in
      response to stress as well as cell wall metabolism. Analysis of the quintuple
      gebp gpl1,2,3 cpr5 mutant indicates that GeBP/GPLs are involved in the control of
      cell expansion in a CPR5-dependent manner but not in the control of cell
      proliferation. In addition, to our knowledge, we provide the first evidence that
      the CPR5 protein is localized in the nucleus of plant cells and that a truncated
      version of the protein with no transmembrane domain can trigger cpr5-like
      processes when fused to the VP16 constitutive transcriptional activation domain.
      Our results provide clues on how CPR5 and GeBP/GPLs play opposite roles in the
      control of cell expansion and suggest that the CPR5 protein is involved in
      transcription.

PMID- 21875894
TI  - Root-localized phytochrome chromophore synthesis is required for photoregulation
      of root elongation and impacts root sensitivity to jasmonic acid in Arabidopsis.
AB  - Plants exhibit organ- and tissue-specific light responses. To explore the
      molecular basis of spatial-specific phytochrome-regulated responses, a transgenic
      approach for regulating the synthesis and accumulation of the phytochrome
      chromophore phytochromobilin (PPhiB) was employed. In prior experiments,
      transgenic expression of the BILIVERDIN REDUCTASE (BVR) gene was used to
      metabolically inactivate biliverdin IXalpha, a key precursor in the biosynthesis
      of PPhiB, and thereby render cells accumulating BVR phytochrome deficient. Here,
      we report analyses of transgenic Arabidopsis (Arabidopsis thaliana) lines with
      distinct patterns of BVR accumulation dependent upon constitutive or tissue
      specific, promoter-driven BVR expression that have resulted in insights on a
      correlation between root-localized BVR accumulation and photoregulation of root
      elongation. Plants with BVR accumulation in roots and a PPhiB-deficient elongated
      hypocotyl2 (hy2-1) mutant exhibit roots that are longer than those of wild-type
      plants under white illumination. Additional analyses of a line with root-specific
      BVR accumulation generated using a GAL4-dependent bipartite enhancer-trap system
      confirmed that PPhiB or phytochromes localized in roots directly impact light
      dependent root elongation under white, blue, and red illumination. Additionally,
      roots of plants with constitutive plastid-localized or root-specific cytosolic
      BVR accumulation, as well as phytochrome chromophore-deficient hy1-1 and hy2-1
      mutants, exhibit reduced sensitivity to the plant hormone jasmonic acid (JA) in
      JA-dependent root inhibition assays, similar to the response observed for the JA
      insensitive mutants jar1 and myc2. Our analyses of lines with root-localized
      phytochrome deficiency or root-specific phytochrome depletion have provided novel
      insights into the roles of root-specific PPhiB, or phytochromes themselves, in
      the photoregulation of root development and root sensitivity to JA.

PMID- 21875895
TI  - Dispersed benzoxazinone gene cluster: molecular characterization and chromosomal
      localization of glucosyltransferase and glucosidase genes in wheat and rye.
AB  - Benzoxazinones (Bxs) are major defensive secondary metabolites in wheat (Triticum
      aestivum), rye (Secale cereale), and maize (Zea mays). Here, we identified full
      sets of homeologous and paralogous genes encoding Bx glucosyltransferase (GT) and
      Bx-glucoside glucosidase (Glu) in hexaploid wheat (2n = 6x = 42; AABBDD). Four GT
      loci (TaGTa-TaGTd) were mapped on chromosomes 7A, 7B (two loci), and 7D, whereas
      four glu1 loci (Taglu1a-Taglu1d) were on chromosomes 2A, 2B (two loci), and 2D.
      Transcript levels differed greatly among the four loci; B-genome loci of both
      TaGT and Taglu1 genes were preferentially transcribed. Catalytic properties of
      the enzyme encoded by each homeolog/paralog also differed despite high levels of
      identity among amino acid sequences. The predominant contribution of the B genome
      to GT and Glu reactions was revealed, as observed previously for the five Bx
      biosynthetic genes, TaBx1 to TaBx5, which are separately located on homeologous
      groups 4 and 5 chromosomes. In rye, where the ScBx1 to ScBx5 genes are dispersed
      to chromosomes 7R and 5R, ScGT and Scglu were located separately on chromosomes
      4R and 2R, respectively. The dispersal of Bx-pathway loci to four distinct
      chromosomes in hexaploid wheat and rye suggests that the clustering of Bx-pathway
      genes, as found in maize, is not essential for coordinated transcription. On the
      other hand, barley (Hordeum vulgare) was found to lack the orthologous GT and glu
      loci like the Bx1 to Bx5 loci despite its close phylogenetic relationship with
      wheat and rye. These results contribute to our understanding of the evolutionary
      processes that the Bx-pathway loci have undergone in grasses.

PMID- 21875896
TI  - RNA PROCESSING FACTOR3 is crucial for the accumulation of mature ccmC transcripts
      in mitochondria of Arabidopsis accession Columbia.
AB  - RNA PROCESSING FACTOR1 (RPF1) and RPF2 are pentatricopeptide repeat (PPR)
      proteins involved in 5' processing of different mitochondrial mRNAs in
      Arabidopsis (Arabidopsis thaliana). Both factors are highly similar to RESTORERS
      OF FERTILITY (RF), which are part of cytoplasmic male sterility/restoration
      systems in various plant species. These findings suggest a predominant role of RF
      like PPR proteins in posttranscriptional 5' processing. To further explore the
      functions of this group of proteins, we examined a number of T-DNA lines carrying
      insertions in the corresponding PPR genes. This screening identified a nearly
      complete absence of mature ccmC transcripts in an At1g62930 T-DNA insertion line,
      a phenotype that could be restored by the introduction of the intact At1g62930
      gene into the mutant. The insertion in this nuclear gene, which we now call RPF3,
      also leads to a severe reduction of the CcmC protein in mitochondria. The
      analysis of C24/rpf3-1 F2 hybrids lacking functional RPF3 genes revealed that
      this gene has less influence on the generation of the mature ccmC 5' transcript
      end derived from a distinct ccmC 5' upstream configuration found in mitochondrial
      DNAs from C24 and other accessions. These data show that a particular function of
      an RF-like protein is required only in connection with a distinct mtDNA
      configuration. Our new results further substantiate the fundamental role of RF
      like PPR proteins in the posttranscriptional generation of plant mitochondrial 5'
      transcript termini.

PMID- 21875897
TI  - Concurrent supplement of estradiol and progesterone reduces the cardiac
      sensitivity to D,L-sotalol-induced arrhythmias in ovariectomized rabbits.
AB  - BACKGROUND: Although the difference in the modulation of estradiol and
      dihydrotesterone on ventricular repolarization has been intensively studied,
      little information is available concerning the role of the different ovarian
      hormones in the modulation of repolarization in the female. METHODS: The chronic
      modulation of female hormones, estradiol, and progesterone, on cardiac
      repolarization and the susceptibility to d,l-sotalol, a class III antiarrhythmic
      agent, were studied in female rabbits by ovariectomy and hormone replacement
      therapy (HRT) through recording and analyzing of electrocardiograms. RESULTS: The
      corrected QT interval (QTc) measured 2 weeks after ovariectomy was not
      significantly different from that in the time-matched control rabbits. After 2
      weeks of HRT, the QTc in the ovariectomized rabbits treated with estradiol alone
      (group E) was not significantly different from that in the control (group C);
      whereas in the ovariectomized rabbits treated with estradiol plus progesterone
      (group E + P), it was significantly shorter than those in groups E (P < .05) and
      C (P < .01), respectively. The corrected Tpeak-end interval (Tpec), an indicator
      of global dispersion of ventricular repolarization, was also significantly
      reduced in group E + P compared with that of group C (P < .01). In group E, d,l
      sotalol-induced prolongation of QTc and the rate and the severity of arrhythmias
      were significantly higher, while the dose of sotalol to initiate arrhythmias was
      significantly lower than those in groups C or E + P, respectively (P < .05 or P <
      .01). CONCLUSION: Estradiol potentiates QTc prolonging effects of d,l-sotalol and
      increases the susceptibility to d,l-sotalol-induced arrhythmias without
      significantly altering QTc itself, whereas progesterone may accelerate the
      process of repolarization and protect the females from drug-induced arrhythmias,
      thus counteracting the effect of estradiol.

PMID- 21875899
TI  - Thirty-five common variants for coronary artery disease: the fruits of much
      collaborative labour.
AB  - Coronary artery disease (CAD) is the leading cause of death worldwide. Affected
      individuals cluster in families in patterns that reflect the sharing of numerous
      susceptibility genes. Genome-wide and large-scale gene-centric genotyping studies
      that involve tens of thousands of cases and controls have now mapped common
      disease variants to 34 distinct loci. Some coronary disease common variants show
      allelic heterogeneity or copy number variation. Some of the loci include
      candidate genes that imply conventional or emerging risk factor-mediated
      mechanisms of disease pathogenesis. Quantitative trait loci associations with
      risk factors have been informative in Mendelian randomization studies as well as
      fine-mapping of causative variants. But, for most loci, plausible mechanistic
      links are uncertain or obscure at present but provide potentially novel
      directions for research into this disease's pathogenesis. The common variants
      explain ~4% of inter-individual variation in disease risk and no more than 13% of
      the total heritability of coronary disease. Although many CAD genes are presently
      undiscovered, it is likely that larger collaborative genome-wide association
      studies will map further common/low-penetrance variants and hoped that low
      frequency or rare high-penetrance variants will also be identified in medical
      resequencing experiments.

PMID- 21875900
TI  - A conserved splicing mechanism of the LMNA gene controls premature aging.
AB  - Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder
      phenotypically characterized by many features of premature aging. Most cases of
      HGPS are due to a heterozygous silent mutation (c.1824C>T; p.Gly608Gly) that
      enhances the use of an internal 5' splice site (5'SS) in exon 11 of the LMNA pre
      mRNA and leads to the production of a truncated protein (progerin) with a
      dominant negative effect. Here we show that HGPS mutation changes the
      accessibility of the 5'SS of LMNA exon 11 which is sequestered in a conserved RNA
      structure. Our results also reveal a regulatory role of a subset of serine
      arginine (SR)-rich proteins, including serine-arginine rich splicing factor 1
      (SRSF1) and SRSF6, on utilization of the 5'SS leading to lamin A or progerin
      production and a modulation of this regulation in the presence of the c.1824C>T
      mutation is shown directly on HGPS patient cells. Mutant mice carrying the
      equivalent mutation in the LMNA gene (c.1827C>T) also accumulate progerin and
      phenocopy the main cellular alterations and clinical defects of HGPS patients.
      RNAi-induced depletion of SRSF1 in the HGPS-like mouse embryonic fibroblasts
      (MEFs) allowed progerin reduction and dysmorphic nuclei phenotype correction,
      whereas SRSF6 depletion aggravated the HGPS-like MEF's phenotype. We demonstrate
      that changes in the splicing ratio between lamin A and progerin are key factors
      for lifespan since heterozygous mice harboring the mutation lived longer than
      homozygous littermates but less than the wild-type. Genetic and biochemical data
      together favor the view that physiological progerin production is under tight
      control of a conserved splicing mechanism to avoid precocious aging.

PMID- 21875901
TI  - A generalizable hypothesis for the genetic architecture of disease: pleomorphic
      risk loci.
AB  - The dominant and sometimes competing theories for the aetiology of complex human
      disease have been the common disease, common variant (CDCV) hypothesis, and the
      multiple rare variant (MRV) hypothesis. With the advent of genome wide
      association studies and of second-generation sequencing, we are fortunate in
      being able to test these ideas. The results to date suggest that these hypotheses
      are not mutually exclusive. Further, initial evidence suggests that both MRV and
      CDCV can be true at the same loci, and that other disease-related genetic
      mechanisms also exist at some of these loci. We propose calling these,
      pleomorphic risk loci, and discuss here how such loci not only offer
      understanding of the genetic basis of disease, but also provide mechanistic
      biological insight into disease processes.

PMID- 21875902
TI  - A synonymous polymorphism of the Tristetraprolin (TTP) gene, an AU-rich mRNA
      binding protein, affects translation efficiency and response to Herceptin
      treatment in breast cancer patients.
AB  - Post-transcriptional regulation plays a central role in cell differentiation and
      proliferation. Among the regulatory factors involved in this mechanism,
      Tristetraprolin (ZFP36 or TTP) is the prototype of a family of RNA-binding
      proteins that bind to adenylate and uridylate (AU)-rich sequences in the 3'UTR of
      mRNAs, which promotes their physiological decay. Here, we investigated whether
      TTP correlates with tumor aggressiveness in breast cancer and is a novel
      prognostic factor for this neoplasia. By immunoblot analysis, we determined the
      amount of TTP protein in different breast cancer cell lines and found an inverse
      correlation between aggressiveness and metastatic potential. TTP mRNA levels were
      very variable among cells lines and did not correlate with protein levels.
      Interestingly, by sequencing the entire TTP coding region in Hs578T cells that do
      not express the TTP protein, we identified a synonymous polymorphism (rs3746083)
      that showed a statistically significant association with a lack of response to
      Herceptin/Trastuzumab in HER2-positive-breast cancer patients. Even though this
      genetic change did not modify the corresponding amino acid, we performed
      functional studies and showed an effect on protein translation associated with
      the variant allele with respect to the wild-type. These data underline the
      importance of synonymous variants on gene expression and the potential role of
      TTP genetic polymorphisms as a prognostic marker for breast cancer.

PMID- 21875903
TI  - Depressive symptoms in first-and second-generation migrants: a cross-sectional
      study of a multi-ethnic working population.
AB  - BACKGROUND: Migrants in Europe may suffer from depression more often than the
      native-born population of the particular host country. Reports about the
      prevalence of depression in migrants are, however, heterogeneous and the possible
      causes are the subject of controversial discussion. AIMS: The aims of this study
      are to determine the incidence of depressiveness in a large multi-ethnic working
      population with and without a history of migration, and to investigate possible
      connections with migration status and acculturation criteria. METHODS: The cross
      sectional study asked 7062 employees of a university hospital to complete a self
      rating questionnaire concerning socio-demographic data, migration status and
      indicators of acculturation. Depressiveness was assessed by means of the German
      version of the Center of Epidemiological Studies Depression Scale (CES-D).
      RESULTS: The response rate was 41.7% (N = 2932); 14.9% of the participants (n =
      419) reported a history of migration, 275 (65.8%) of whom were first-generation
      (M1) and 143 (34.2%) second-generation (M2) migrants. According to the CES-D
      scores, 8.7% of non-migrants (n = 207) suffered from clinically relevant
      depressive symptoms, compared to 16% (n = 44) of the M1 group (OR = 2.10, 95% CI:
      1.44-3.04, p < .001) and 14% (n = 20) in M2 (OR = 1.68, 95% CI: 1.01-2.79, p =
      .048). Taking gender into consideration revealed that only the female migrants
      showed a statistically significant increased rate of depressiveness (chi (2) =
      16.68, p < .001). CONCLUSIONS: Our results suggest that first- and second
      generation female migrants are more likely to suffer from depressiveness than non
      migrant females. In this model a history of migration is shown to be an
      independent risk factor for depressiveness.

PMID- 21875905
TI  - Utilization and implementation of trauma-focused cognitive-behavioral therapy for
      the treatment of maltreated children.
AB  - Trauma-Focused Cognitive-Behavioral Therapy (TF-CBT) is one of the most
      researched and widely disseminated interventions for maltreated children. This
      study describes the findings of a survey of 132 mental health clinicians in
      children's advocacy centers (CACs) across the United States to determine the
      percentage of clinicians who are trained in and utilize TF-CBT and the frequency
      with which TF-CBT components are implemented. A total of 103 (78%) of the
      clinicians reported being trained in and utilizing TF-CBT on a regular basis;
      however, only 66% of these clinicians (58% of the full sample) reported being
      likely to use each component. The most preferred components were teaching
      relaxation skills and providing psychoeducation, whereas teaching caregiver child
      behavior management skills, developing a trauma narrative, and cognitive
      restructuring were less preferred. Results are discussed in the context of
      continued dissemination efforts and implications for improving clinical practice.

PMID- 21875904
TI  - Endothelial nitric oxide synthase enhancer reduces oxidative stress and restores
      endothelial function in db/db mice.
AB  - AIMS: Endothelial dysfunction is caused by reduced nitric oxide (NO)
      bioavailability and/or over-produced reactive oxygen species (ROS). The present
      study investigated a vascular benefit of AVE3085, an endothelial nitric oxide
      synthase (eNOS) enhancer, in preserving endothelial function in diabetic mice and
      the mechanisms involved. METHODS AND RESULTS: Male db/db and db/m(+) mice were
      orally administered AVE3085 for 7 days (10 mg kg(-1) day(-1)). Vascular
      reactivity of arteries was studied via myography under both isometric and
      isobaric conditions. ROS levels in aortas were determined using dihydroethidium
      fluorescence dye and electron paramagnetic resonance spin trapping. Chronic
      treatment with AVE3085 reduced blood pressure, enhanced endothelium-dependent
      relaxations (EDR) to acetylcholine in aortas, mesenteric, and renal arteries,
      lowered oxidative stress, and augmented the attenuated flow-dependent dilatation
      in mesenteric resistance arteries from db/db mice. Incubation of aortas from
      C57BL/6J mice in high glucose (30 mmol L(-1)) culture medium for 48 h impaired
      EDR and elevated ROS generation, and these effects were reversed by co-treatment
      with AVE3085 (1 umol L(-1)). Benefits of AVE3085 were abolished by the
      transcription inhibitor actinomycin D, the NOS inhibitor N(G)-nitro-L-arginine
      methyl ester, and in eNOS(-/-) mice. NO production in primary endothelial cells
      from mouse aortas was detected with a NO-sensitive fluorescence dye. Protein
      expression was assayed by western blotting. Treatment with AVE3085 enhanced NO
      production in endothelial cells and eNOS expression in aortas. CONCLUSION:
      AVE3085 ameliorates endothelial dysfunction in db/db mice through increased NO
      bioavailability, which reduces oxidative stress in the vascular wall. Targeting
      eNOS and NO production may be a promising approach to combat diabetic
      vasculopathy.

PMID- 21875906
TI  - ACCF/AHA methodology for the development of quality measures for cardiovascular
      technology: a report of the American College of Cardiology Foundation/American
      Heart Association Task Force on Performance Measures.
AB  - Consistent with the growing national focus on healthcare quality, the American
      College of Cardiology Foundation (ACCF) and the American Heart Association (AHA)
      have taken a leadership role over the past decade in developing measures of the
      quality of cardiovascular care by convening a joint ACCF/AHA Task Force on
      Performance Measures. The Task Force is charged with identifying the clinical
      topics appropriate for the development of performance measures and with
      assembling writing committees composed of clinical and methodological experts in
      collaboration with appropriate subspecialty societies. The Task Force has also
      created methodology documents that offer guidance in the development of process,
      outcome, composite, and efficiency measures. Cardiovascular performance measures
      using existing ACCF/AHA methodology are based on Class I or Class III guidelines
      recommendations, usually with Level A evidence. These performance measures, based
      on evidence-based ACCF/AHA guidelines, remain the most rigorous quality measures
      for both internal quality improvement and public reporting. However, many of the
      tools for diagnosis and treatment of cardiovascular disease involve advanced
      technologies, such as cardiac imaging, for which there are often no underlying
      guideline documents. Because these technologies affect the quality of
      cardiovascular care and also have the potential to contribute to cardiovascular
      health expenditures, there is a need for more critical assessment of the use of
      technology, including the development of quality and performance measures in
      areas in which guideline recommendations are absent. The evaluation of quality in
      the use of cardiovascular technologies requires consideration of multiple
      parameters that differ from other healthcare processes. The present document
      describes methodology for development of 2 new classes of quality measures in
      these situations, appropriate use measures and structure/safety measures.
      Appropriate use measures are based on specific indications, processes, or
      parameters of care for which high level of evidence data and Class I or Class III
      guideline recommendations may be lacking but are addressed in ACCF appropriate
      use criteria documents. Structure/safety measures represent measures developed to
      address structural aspects of the use of healthcare technology (e.g., laboratory
      accreditation, personnel training, and credentialing) or quality issues related
      to patient safety when there are neither guidelines recommendations nor
      appropriate use criteria. Although the strength of evidence for appropriate use
      measures and structure/safety measures may not be as strong as that for formal
      performance measures, they are quality measures that are otherwise rigorously
      developed, reviewed, tested, and approved in the same manner as ACCF/AHA
      performance measures. The ultimate goal of the present document is to provide
      direction in defining and measuring the appropriate use-avoiding not only
      underuse but also overuse and misuse-and proper application of cardiovascular
      technology and to describe how such appropriate use measures and structure/safety
      measures might be developed for the purposes of quality improvement and public
      reporting. It is anticipated that this effort will help focus the national
      dialogue on the use of cardiovascular technology and away from the current
      concerns about volume and cost alone to a more holistic emphasis on value.

PMID- 21875907
TI  - Long-term outcome of patients with isolated thin discrete subaortic stenosis
      treated by balloon dilation: a 25-year study.
AB  - BACKGROUND: Transluminal balloon tearing of the membrane in a thin discrete
      subaortic stenosis is an alternative to membrane surgical resection. However, the
      long-term outcome of patients with isolated thin discrete subaortic stenosis
      treated by transluminal balloon tearing remains unknown. METHODS AND RESULTS:
      This 25-year study describes findings from 76 patients with isolated thin
      discrete subaortic stenosis who underwent percutaneous transluminal balloon
      tearing of the membrane and were followed up for a mean period of 16+/-6 years.
      The age at presentation had a wide range (2-67 years). The mean age at treatment
      was 19+/-16 years. Immediately after treatment, the subvalvular gradient
      decreased from 70+/-27 to 18+/-12 mm Hg (P<0.001). No significant postprocedural
      aortic regurgitation was observed. After a mean follow-up time of 16+/-6 years,
      11 patients (15%) developed restenosis, 3 patients (4%) progressed to muscular
      obstructive disease, and 1 patient (1.3%) developed a new distant obstructive
      membrane. Twelve patients (16%) were redilated at a mean of 5+/-3 years after
      their first treatment, and 4 patients (5%) underwent surgery at a mean of 3+/-2
      years after their first treatment. Fifty-eight patients (77%) remained alive and
      free of redilation or surgery at follow-up. Larger annulus diameter and thinner
      membranes were independent factors associated with better long-term results.
      CONCLUSIONS: Most patients (77%) with isolated thin discrete subaortic stenosis
      treated with transluminal balloon tearing of the membrane had sustained relief at
      subsequent follow-ups without restenosis, the need for surgery, progression to
      muscular obstructive disease, or an increase in the degree of aortic
      regurgitation.

PMID- 21875908
TI  - Mortality and neurologic injury after surgical repair with hypothermic
      circulatory arrest in acute and chronic proximal thoracic aortic pathology:
      effect of age on outcome.
AB  - BACKGROUND: The goal of this study was to determine whether advanced age affects
      mortality and incidence of neurological injury in patients undergoing surgical
      repair with hypothermic circulatory arrest in acute and chronic thoracic aortic
      pathology. METHODS AND RESULTS: A university center audit was done of 523
      consecutive patients (median age, 64 years; interquartile range, 56-71 years)
      between 2005 and 2010. Mortality in acute type A aortic dissection (207 patients)
      was 9.7%, and in chronic ascending aortic aneurysms (316 patients) was 2.2%
      (P<0.001). Neurological injury was observed in 16.9% of patients with acute type
      A aortic dissection (chronic ascending aortic aneurysms, 7.9%; P=0.002).
      Multivariable regression analysis revealed hypothermic circulatory arrest >40
      minutes (odds ratio [OR], 4.21; 95% confidence interval [CI], 1.60-11.06;
      P=0.004) and redo surgery (OR, 3.44; 95% CI, 1.11-10.64; P=0.03) but not age (OR,
      1.98; 95% CI, 0.73-5.38; P=0.18) as independent predictor of mortality. Emergency
      surgery (OR, 3.27; 95% CI, 1.31-8.15; P=0.01) and extracardiac arteriopathy (OR,
      2.38; 95% CI, 1.26-4.50; P=0.008) but not age (OR, 1.80; 95% CI, 0.93-3.48;
      P=0.08) were independent predictors of neurological injury. CONCLUSIONS: Age is
      not associated with increased risk for mortality and neurological injury in
      patients undergoing surgical repair for acute and chronic thoracic aortic
      pathology with hypothermic circulatory arrest. Extended hypothermic circulatory
      arrest times, reflecting the extent of disease, and redo surgery predict
      mortality, whereas emergency surgery and extracardiac arteriopathy predict
      neurological injury.

PMID- 21875909
TI  - Delayed postconditioning in the mouse heart in vivo.
AB  - BACKGROUND: Reperfusion during acute myocardial infarction remains the best
      treatment for reducing infarct size. Postconditioning, applied at the onset of
      reperfusion, reduces myocardial infarction both in animals and humans. The
      objective of this study was to identify the time delay to apply postconditioning
      at reperfusion, allowing preservation of cardioprotection in the mouse
      myocardium. This is a major issue in the management of acute myocardial
      infarction patients. METHODS AND RESULTS: Mice were subjected to 40 minutes of
      ischemia and 60 minutes of reperfusion (IR(60')). Postconditioning protocols
      corresponding to repetitive ischemia (3 cycles of 1 minute of ischemia and 1
      minute of reperfusion) were applied during early reperfusion at various time
      durations (Deltat) after reopening of the coronary artery (Deltat=10 seconds, 1,
      5, 10, 15, 20, 30, and 45 minutes; PostC(Deltat)). Infarct size/area at risk was
      reduced by 71% in PostC(Delta1) compared with IR(60') mice (P=5*10(-6)). There
      was a linear correlation (r(2)=0.91) between infarct size and Deltat, indicating
      that the cardioprotective effect of delayed postconditioning was progressively
      attenuated when Deltat time increased. The protective effect of PostC(Delta1) and
      PostC(Delta15) was still effective when the duration of reperfusion was prolonged
      to 24 hours (IR(24 hours); PostC(Delta1) and PostC(Delta15) versus IR(24 hours),
      P=0.001). Similar results were obtained for internucleosomal DNA fragmentation
      and lactate dehydrogenase release. CONCLUSIONS: This study in our in vivo mouse
      model of myocardial IR shows for the first time that delaying the intervention of
      postconditioning to 30 minutes does not abrogate the cardioprotective effect of
      postconditioning. This finding provides evidence that the time window of
      protection afforded by postconditioning may be larger than initially reported.

PMID- 21875910
TI  - Lysozyme M-positive monocytes mediate angiotensin II-induced arterial
      hypertension and vascular dysfunction.
AB  - BACKGROUND: Angiotensin II (ATII), a potent vasoconstrictor, causes hypertension,
      promotes infiltration of myelomonocytic cells into the vessel wall, and
      stimulates both vascular and inflammatory cell NADPH oxidases. The predominant
      source of reactive oxygen species, eg, vascular (endothelial, smooth muscle,
      adventitial) versus phagocytic NADPH oxidase, and the role of myelomonocytic
      cells in mediating arterial hypertension have not been defined yet. METHODS AND
      RESULTS: Angiotensin II (1 mg . kg(-1) . d(-1) for 7 days) increased the number
      of both CD11b(+)Gr-1(low)F4/80(+) macrophages and CD11b(+)Gr-1(high)F4/80(-)
      neutrophils in mouse aorta (verified by flow cytometry). Selective ablation of
      lysozyme M-positive (LysM(+)) myelomonocytic cells by low-dose diphtheria toxin
      in mice with inducible expression of the diphtheria toxin receptor (LysM(iDTR)
      mice) reduced the number of monocytes in the circulation and limited ATII-induced
      infiltration of these cells into the vascular wall, whereas the number of
      neutrophils was not reduced. Depletion of LysM(+) cells attenuated ATII-induced
      blood pressure increase (measured by radiotelemetry) and vascular endothelial and
      smooth muscle dysfunction (assessed by aortic ring relaxation studies) and
      reduced vascular superoxide formation (measured by chemiluminescence, cytochrome
      c assay, and oxidative fluorescence microtopography) and the expression of NADPH
      oxidase subunits gp91(phox) and p67(phox) (assessed by Western blot and mRNA
      reverse-transcription polymerase chain reaction). Adoptive transfer of wild-type
      CD11b(+)Gr-1(+) monocytes into depleted LysM(iDTR) mice reestablished ATII
      induced vascular dysfunction, oxidative stress, and arterial hypertension,
      whereas transfer of CD11b(+)Gr-1(+) neutrophils or monocytes from gp91(phox) or
      ATII receptor type 1 knockout mice did not. CONCLUSIONS- Infiltrating monocytes
      with a proinflammatory phenotype and macrophages rather than neutrophils appear
      to be essential for ATII-induced vascular dysfunction and arterial hypertension.

PMID- 21875911
TI  - Adolescents with d-transposition of the great arteries corrected with the
      arterial switch procedure: neuropsychological assessment and structural brain
      imaging.
AB  - BACKGROUND: We report neuropsychological and structural brain imaging assessments
      in children 16 years of age with d-transposition of the great arteries who
      underwent the arterial switch operation as infants. Children were randomly
      assigned to a vital organ support method, deep hypothermia with either total
      circulatory arrest or continuous low-flow cardiopulmonary bypass. METHODS AND
      RESULTS: Of 159 eligible adolescents, 139 (87%) participated. Academic
      achievement, memory, executive functions, visual-spatial skills, attention, and
      social cognition were assessed. Few significant treatment group differences were
      found. The occurrence of seizures in the postoperative period was the medical
      variable most consistently related to worse outcomes. The scores of both
      treatment groups tended to be lower than those of the test normative populations,
      with substantial proportions scoring >=1 SDs below the expected mean. Although
      the test scores of most adolescents in this trial cohort are in the average
      range, a substantial proportion have received remedial academic or behavioral
      services (65%). Magnetic resonance imaging abnormalities were more frequent in
      the d-transposition of the great arteries group (33%) than in a referent group
      (4%). CONCLUSIONS: Adolescents with d-transposition of the great arteries who
      have undergone the arterial switch operation are at increased neurodevelopmental
      risk. These data suggest that children with congenital heart disease may benefit
      from ongoing surveillance to identify emerging difficulties. CLINICAL TRIAL
      REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000470.

PMID- 21875912
TI  - Exercise oscillatory ventilation in systolic heart failure: an indicator of
      impaired hemodynamic response to exercise.
AB  - BACKGROUND: Exercise oscillatory ventilation (EOV) is a noninvasive parameter
      that potently predicts outcomes in systolic heart failure (HF). However,
      mechanistic insights into EOV have been limited by the absence of studies
      relating EOV to invasive hemodynamic measurements and blood gases performed
      during exercise. METHODS AND RESULTS: Fifty-six patients with systolic HF (mean+/
      SEM age, 59+/-2 years; left ventricular ejection fraction, 30+/-1%) and 19 age
      matched control subjects were studied with incremental cardiopulmonary exercise
      testing. Fick cardiac outputs, filling pressures, and arterial blood gases were
      measured at 1-minute intervals during exercise. We detected EOV in 45% of HF
      (HF+EOV) patients and in none of the control subjects. The HF+EOV group did not
      differ from the HF patients without EOV (HF-EOV) in age, sex, body mass index,
      left ventricular ejection fraction, or origin of HF. Univariate predictors of the
      presence of EOV in HF, among measurements performed during exercise, included
      higher right atrial pressure and pulmonary capillary wedge pressure and lower
      cardiac index (CI) but not Paco2 or Pao2. Multivariate logistic regression
      identified that low exercise CI is the strongest predictor of EOV (odds ratio,
      1.39 for each 1.0-L . min(-1) . m(-2) decrement in CI; 95% confidence interval,
      1.14-1.70; P=0.001). Among HF patients with EOV, exercise CI was inversely
      related to EOV cycle length (R=-0.71) and amplitude (R=-0.60; both P<0.001). In
      11 HF+EOV subjects treated with 12 weeks of sildenafil, EOV cycle length and
      amplitude decreased proportionately to increases in CI. CONCLUSION: Exercise
      oscillatory ventilation is closely related to reduced CI and elevated filling
      pressures during exercise and may be an important surrogate for exercise-induced
      hemodynamic impairment in HF patients. Clinical Trial Registration- URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00309790.

PMID- 21875913
TI  - Platelet reactivity and cardiovascular outcomes after percutaneous coronary
      intervention: a time-dependent analysis of the Gauging Responsiveness with a
      VerifyNow P2Y12 assay: Impact on Thrombosis and Safety (GRAVITAS) trial.
AB  - BACKGROUND: In the Gauging Responsiveness With A VerifyNow P2Y12 Assay: Impact on
      Thrombosis and Safety (GRAVITAS) trial, 6 months of high-dose clopidogrel did not
      reduce cardiovascular events compared with standard-dose clopidogrel in patients
      with high on-treatment platelet reactivity (OTR) after percutaneous coronary
      intervention, defined as OTR >=230 P2Y12 reaction units according to the
      VerifyNow P2Y12 platelet function test. The aim of this analysis was to examine
      the relationship between outcomes and OTR over the course of the trial. METHODS
      AND RESULTS: OTR was measured at 12 to 24 hours and 30+/-7 days after
      percutaneous coronary intervention. Cox proportional hazards models with OTR as a
      time-varying covariate were used to determine the association between OTR and the
      primary end point of cardiovascular death, myocardial infarction, and stent
      thrombosis. Of the 2800 enrolled patients, 2796 (99.98%) had evaluable platelet
      function data. OTR <208 P2Y12 reaction units was significantly associated with a
      lower risk of the primary end point at 60 days (hazard ratio, 0.18; 95%
      confidence interval, 0.04 to 0.79; P=0.02) and at 6 months (hazard ratio, 0.43;
      95% confidence interval, 0.23 to 0.82; P=0.01). After adjustment for other
      significant predictors of outcome, OTR <208 P2Y12 reaction units remained
      independently associated with the primary end point at 60 days (hazard ratio,
      0.23; 95% confidence interval, 0.05 to 0.98; P=0.047) and tended to be associated
      at 6 months (adjusted hazard ratio, 0.54; 95% confidence interval, 0.28 to 1.04;
      P=0.065). CONCLUSIONS: In the GRAVITAS trial, achievement of on-clopidogrel
      reactivity <208 P2Y12 reaction units at 12 to 24 hours after percutaneous
      coronary intervention or during follow-up was associated with a lower risk for
      cardiovascular events. The efficacy of an individualized strategy to target a
      level of OTR below this threshold merits investigation. Clinical Trial
      Registration- http://www.clinicaltrials.gov. Unique identifier: NCT00645918.

PMID- 21875914
TI  - A palpable source of stroke.

PMID- 21875916
TI  - Letter by Maass and Maier regarding article, "Cardiac arrhythmogenic remodeling
      in a rat model of long-term intensive exercise training".

PMID- 21875917
TI  - Letter by Ruiz et al regarding article, "Cardiac arrhythmogenic remodeling in a
      rat model of long-term intensive exercise training".

PMID- 21875918
TI  - Letter by Nunes regarding article, "Clinical cardiology: physician update:
      erectile dysfunction and cardiovascular disease".

PMID- 21875919
TI  - Defining the disconnect between in vitro models and human arrhythmogenic disease:
      context matters.

PMID- 21875920
TI  - Importance of family history as a risk factor for venous thromboembolism.

PMID- 21875921
TI  - Prevention and recovery of hibernating myocardium by microvascular repair.

PMID- 21875922
TI  - Cardiac amyloidosis: a treatable disease, often overlooked.

PMID- 21875923
TI  - Large thrombus originating from left atrial diverticulum: a new concern for
      catheter ablation of atrial fibrillation.

PMID- 21875924
TI  - Survey of the performance of commercial dose calibrators for measurement of 123I
      activity.
AB  - The accuracy with which (123)I activity is measured by a dose calibrator depends
      on the composition and geometry of the source. The present study assessed the
      variability of current commercial dose calibrators in assaying liquid (123)I
      samples. METHODS: A calibration procedure for (123)I measurement was performed on
      177 dose calibrators (11 manufacturers) at 138 sites in North America and Europe.
      Using the standard (123)I push-button or dial setting, activity in a 5-mL (123)I
      calibration source in a 10-mL U.S. Pharmacopeia type 1 glass vial (actual
      activity previously determined using a National Institute of Standards and
      Technology-traceable standard metrology chamber) was measured. A portion of the
      source was then transferred to a plastic syringe (10-, 5-, and 3-mL sizes at
      different sites), and the activity in the syringe was measured. Calibration
      factors (CFs) for converting the dose calibrator readings to the reference
      activities were then determined for the vial and the syringes. Data were analyzed
      for all calibrators combined and based on device manufacturers. Measurements
      using a copper attenuator (sleeve) were made for a subset of 10 dose calibrators
      at sites that used these devices in clinical practice. RESULTS: Mean CFs for the
      different measurements were as follows: 10-mL vial, 1.278; 10-mL syringe, 0.811;
      5-mL syringe, 0.815; 3-mL syringe, 0.792. Almost half of the dose calibrators had
      vial CFs between 1.2 and 1.3 and 10-mL syringe CFs between 0.7 and 0.8, whereas
      less than 16% of the instruments had uncorrected readings within +/-10% of the
      reference activities. Although there was a wide range of CFs for different
      calibrators using the copper sleeve, for each unit the CFs for the glass vial and
      the 10-mL plastic syringe were virtually identical. CONCLUSION: On most
      commercial dose calibrators, the standard (123)I settings result in significant
      errors in activity measurements for sources in glass vials and plastic syringes.
      The difference in ionization chamber detection caused by the container
      composition (glass vs. plastic) is a much larger source of measurement variation
      than source volume or geometry.

PMID- 21875925
TI  - Hepatic galactose metabolism quantified in humans using 2-18F-fluoro-2-deoxy-D
      galactose PET/CT.
AB  - Accurate quantification of regional liver function is needed, and PET of specific
      hepatic metabolic pathways offers a unique method for this purpose. Here, we
      quantify hepatic galactose elimination in humans using PET and the galactose
      analog 2-(18)F-fluoro-2-deoxy-d-galactose ((18)F-FDGal) as the PET tracer.
      METHODS: Eight healthy human subjects underwent (18)F-FDGal PET/CT of the liver
      with and without a simultaneous infusion of galactose. Hepatic systemic clearance
      of (18)F-FDGal was determined from linear representation of the PET data. Hepatic
      galactose removal kinetics were determined using measurements of hepatic blood
      flow and arterial and liver vein galactose concentrations at increasing galactose
      infusions. The hepatic removal kinetics of (18)F-FDGal and galactose and the
      lumped constant (LC) were determined. RESULTS: The mean hepatic systemic
      clearance of (18)F-FDGal was significantly higher in the absence than in the
      presence of galactose (0.274 +/- 0.001 vs. 0.019 +/- 0.001 L blood/min/L liver
      tissue; P < 0.01), showing competitive substrate inhibition of galactokinase. The
      LC was 0.13 +/- 0.01, and the (18)F-FDGal PET with galactose infusion provided an
      accurate measure of the local maximum removal rate of galactose (V(max)) in liver
      tissue compared with the V(max) estimated from arterio-liver venous (A-V)
      differences (1.41 +/- 0.24 vs. 1.76 +/- 0.08 mmol/min/L liver tissue; P = 0.60).
      The first-order hepatic systemic clearance of (18)F-FDGal was enzyme-determined
      and can thus be used as an indirect estimate of galactokinase capacity without
      the need for galactose infusion or knowledge of the LC. CONCLUSION: (18)F-FDGal
      PET/CT provides an accurate in vivo measurement of human galactose metabolism,
      which enables the quantification of regional hepatic metabolic function.

PMID- 21875927
TI  - Acupuncture in palliative care.

PMID- 21875928
TI  - Methodological advances needed in analysis and interpretation of sham acupuncture
      validation studies.

PMID- 21875929
TI  - Evaluation of acupuncture in the management of chemotherapy-induced peripheral
      neuropathy.
AB  - AIM: To clinically evaluate the effectiveness of acupuncture when used in the
      management of chemotherapy-induced peripheral neuropathy (PN). BACKGROUND: During
      cancer treatment, certain chemotherapies can cause varying degrees of PN.
      Patients' quality of life can be seriously impaired through loss of sensation,
      pain or mobility problems. Conventional medications routinely used to manage
      neuropathic symptoms have poor side-effect profiles and there is little or no
      evidence justifying their use to treat chemotherapy-related neurotoxicities.
      There are studies suggesting that acupuncture may be an effective therapy in
      treating PN across a number of different aetiologies. Design A retrospective
      service evaluation. METHOD: Patients (n=18) were referred for acupuncture by the
      medical staff and/ornurse specialists or they self-referred for treatment. A
      course of six weekly acupuncture sessions was offered to them, and their details
      were recorded on an evaluation form prior to session one. Points were selected by
      acupuncturists, based on patient presentation, and needles remained in situ for
      30-45 min. Treatments took place in outpatient clinics, chemotherapy day case
      ward or a drop-in clinic based in a physiotherapy gym. The evaluation form was
      completed at the end of session 6 by a therapist who had not been involved in
      patient care. RESULTS: 82% (n=14) of patients reported an improvement in symptoms
      following their course of acupuncture; one patient with advanced disease died
      during the 6 weeks. Some patients derived additional benefits from the treatment
      including a reduction in analgesic use and improved sleeping patterns. The most
      common acupoints used were SP6 (n=18), ST36 (n=18) and LV3 (n=14). CONCLUSION:
      Although these results are encouraging, they are uncontrolled. They suggest that
      acupuncture could be an option for these patients and controlled trials using
      validated patient-reported outcome measures are justified.

PMID- 21875930
TI  - Recent papers summarised by Adrian White.

PMID- 21875931
TI  - ADAM12 produced by tumor cells rather than stromal cells accelerates breast tumor
      progression.
AB  - Expression of ADAM12 is low in most normal tissues but is markedly increased in
      numerous human cancers, including breast carcinomas. We have previously shown
      that overexpression of ADAM12 accelerates tumor progression in a mouse model of
      breast cancer (PyMT). In this study, we found that ADAM12 deficiency reduces
      breast tumor progression in the PyMT model. However, the catalytic activity of
      ADAM12 seems to be dispensable for its tumor-promoting effect. Interestingly, we
      show that ADAM12 endogenously expressed in tumor-associated stroma in the PyMT
      model does not influence tumor progression, but that ADAM12 expression by tumor
      cells is necessary for tumor progression in these mice. This finding is
      consistent with our observation that in human breast carcinoma, ADAM12 is almost
      exclusively located in tumor cells and, only rarely, seen in the tumor-associated
      stroma. We hypothesized, however, that the tumor-associated stroma may stimulate
      ADAM12 expression in tumor cells, on the basis of the fact that TGF-beta1
      stimulates ADAM12 expression and is a well-known growth factor released from
      tumor-associated stroma. TGF-beta1 stimulation of ADAM12-negative Lewis lung
      tumor cells induced ADAM12 synthesis, and growth of these cells in vivo induced
      more than 200-fold increase in ADAM12 expression. Our observation that ADAM12
      expression is significantly higher in the terminal duct lobular units (TDLU)
      adjacent to human breast carcinoma compared with TDLUs found in normal breast
      tissue supports our hypothesis that tumor-associated stroma triggers ADAM12
      expression.

PMID- 21875932
TI  - miR-31 is a broad regulator of beta1-integrin expression and function in cancer
      cells.
AB  - Integrins are adhesion receptors involved in bidirectional signaling that are
      crucial for various cellular responses during normal homeostasis and pathologic
      conditions such as cancer progression and metastasis. Aberrant expression of
      noncoding microRNAs (miRNA) has been implicated in the deregulation of integrin
      expression and activity, leading to the development and progression of cancer
      tumors, including their acquisition of the metastatic phenotype. miR-31 is a key
      regulator of several critical genes involved in the invasion-metastasis cascade
      in cancer. Using diverse cell-based, genetic, biochemical, flow cytometry, and
      functional analyses, we report that miR-31 is a master regulator of integrins as
      it targets multiple alpha subunit partners (alpha2, alpha5, and alphaV) of beta1
      integrins and also beta3 integrins. We found that expression of miR-31 in cancer
      cells resulted in a significant repression of these integrin subunits both at the
      mRNA and protein levels. Loss of expression of alpha2, alpha5, alphaV, and beta3
      was a direct consequence of miR-31 targeting conserved seed sequences in the 3'
      untranslated region of these integrin subunits leading to their
      posttranscriptional repression, which was reflected in their diminished surface
      expression in live cells. The biological consequence of decreased the cell
      surface of these integrins was a significant inhibition of cell spreading in a
      ligand-dependent manner. Although different reports have shown that a single
      integrin can be regulated by several miRNAs, here we show that a single miRNA,
      miR-31, is able to specifically target several integrin subunits to regulate key
      aspects of cancer cell invasion and metastasis.

PMID- 21875933
TI  - Proteolytic activation of pro-macrophage-stimulating protein by hepsin.
AB  - Macrophage-stimulating protein (MSP) is a plasminogen-related growth factor and
      ligand for the receptor tyrosine kinase RON. The MSP/RON system promotes wound
      healing and invasive tumor growth and suppresses proinflammatory immune response.
      MSP binding to RON requires proteolytic conversion of the inactive single-chain
      form (pro-MSP) into the disulfide-linked alpha/beta heterodimer. The pro-MSP
      cleavage sequence (Ser-Lys-Leu-Arg(483)?Val(484)) closely matches the substrate
      recognition sequences of hepsin, a type II transmembrane serine protease, that is
      overexpressed in several cancers. Here, we show that recombinant hepsin cleaves
      pro-MSP at the consensus site Arg(483)-Val(484) with superior efficiency compared
      with the known activators MT-SP1 and hepatocyte growth factor activator (HGFA).
      At least 50% of pro-MSP was processed within 1 hour at a hepsin concentration of
      2.4 nmol/L and at a molar enzyme to substrate ratio of 1:500. An uncleavable
      single-chain variant of MSP weakly bound to a RON-Fc fusion protein, whereas
      hepsin-cleaved MSP bound with a K(D) of 10.3 nmol/L, suggesting that the high
      affinity binding site in MSP beta-chain was properly formed. LNCaP prostate
      cancer cells overexpressing hepsin on the cell surface efficiently activated pro
      MSP, which was blocked by a specific anti-hepsin antibody. Incubation of pro-MSP
      with hepsin led to robust RON-mediated phosphorylation of mitogen-activated
      protein kinase, ribosomal S6 protein, and Akt in human A2780 ovarian carcinoma
      cells stably expressing RON protein. In macrophages, pro-MSP with hepsin induced
      chemotaxis and attenuated lipopolysaccharide-dependent production of nitric
      oxide. These findings suggest that the MSP/RON signaling pathway may be regulated
      by hepsin in tissue homeostasis and in disease pathologies, such as in cancer and
      immune disorders.

PMID- 21875934
TI  - What fraction of the human genome is functional?
AB  - Many evolutionary studies over the past decade have estimated alpha(sel), the
      proportion of all nucleotides in the human genome that are subject to purifying
      selection because of their biological function. Most of these studies have
      estimated the nucleotide substitution rates from genome sequence alignments
      across many diverse mammals. Some alpha(sel) estimates will be affected by the
      heterogeneity of substitution rates in neutral sequence across the genome. Most
      will also be inaccurate if change in the functional sequence repertoire occurs
      rapidly relative to the separation of lineages that are being compared. Evidence
      gathered from both evolutionary and experimental analyses now indicate that rates
      of "turnover" of functional, predominantly noncoding, sequence are, indeed, high.
      They are sufficiently high that an estimated 50% of mouse constrained noncoding
      sequence is predicted not to be shared with rat, a closely related rodent. The
      rapidity of turnover results in, at least, a twofold underestimate of alpha(sel)
      by analyses that measure constraint across the eutherian phylogeny. Approaches
      that take account of turnover estimate that the steady-state value of alpha(sel)
      lies between 10% and 15%. Experimental studies corroborate the predicted rates of
      loss and gain of noncoding functional sites. These studies show the limitations
      inherent in the use of deep sequence conservation for identifying functional
      sequence. Experimental investigations focusing on lineage-specific, noncoding,
      and functional sequence are now essential if we are to appreciate the complete
      functional repertoire of the human genome.

PMID- 21875937
TI  - Surgical outcomes of multicentric adenocarcinomas of the biliary tract.
AB  - OBJECTIVE: In comparison to single biliary cancers, distinct features of biliary
      multicentric adenocarcinomas are not yet clear. METHODS: From July 1992 to July
      2009, 393 patients underwent surgery for cancers of the biliary tract at the
      National Cancer Center Hospital East, Kashiwa, Japan. Clinicopathological
      characteristics and surgical outcomes of multicentric biliary adenocarcinoma were
      compared with those of single cancers. RESULTS: During the period, 10 cases
      (2.5%) with multicentric cancer (6 synchronous and 4 metachronous cancers) were
      found among 393 cases of biliary cancer. Pathologically, compared with single
      cancers, multicentric adenocarcinomas were more likely to be early cancers and to
      be papillary carcinomas with both superficial epithelial tumor spread and
      extensive dysplastic epithelium, but were less likely to have lymph node
      metastases (P < 0.01). The proportion of multicentric cancers among early
      papillary cancers was high (9/24, 37.5%). Clinically, no recurrences were
      detected in lymph nodes, peritoneum or distant organs, but one recurrence in the
      remnant bile duct. Only one patient died from cancer progression. The overall
      survival of patients with multicentric adenocarcinomas was statistically the same
      as that of single cancers (median survival: 69 vs. 30 months, P = 0.47).
      CONCLUSIONS: Multicentric adenocarcinomas of the biliary tract have distinct
      features compared with single cancers.

PMID- 21875935
TI  - Discriminative prediction of mammalian enhancers from DNA sequence.
AB  - Accurately predicting regulatory sequences and enhancers in entire genomes is an
      important but difficult problem, especially in large vertebrate genomes. With the
      advent of ChIP-seq technology, experimental detection of genome-wide EP300/CREBBP
      bound regions provides a powerful platform to develop predictive tools for
      regulatory sequences and to study their sequence properties. Here, we develop a
      support vector machine (SVM) framework which can accurately identify EP300-bound
      enhancers using only genomic sequence and an unbiased set of general sequence
      features. Moreover, we find that the predictive sequence features identified by
      the SVM classifier reveal biologically relevant sequence elements enriched in the
      enhancers, but we also identify other features that are significantly depleted in
      enhancers. The predictive sequence features are evolutionarily conserved and
      spatially clustered, providing further support of their functional significance.
      Although our SVM is trained on experimental data, we also predict novel enhancers
      and show that these putative enhancers are significantly enriched in both ChIP
      seq signal and DNase I hypersensitivity signal in the mouse brain and are located
      near relevant genes. Finally, we present results of comparisons between other
      EP300/CREBBP data sets using our SVM and uncover sequence elements enriched
      and/or depleted in the different classes of enhancers. Many of these sequence
      features play a role in specifying tissue-specific or developmental-stage
      specific enhancer activity, but our results indicate that some features operate
      in a general or tissue-independent manner. In addition to providing a high
      confidence list of enhancer targets for subsequent experimental investigation,
      these results contribute to our understanding of the general sequence structure
      of vertebrate enhancers.

PMID- 21875938
TI  - A consensus-based guideline defining clinical target volume for primary disease
      in external beam radiotherapy for intact uterine cervical cancer.
AB  - OBJECTIVE: To develop a consensus-based guideline to define clinical target
      volume for primary disease (clinical target volume primary) in external beam
      radiotherapy for intact uterine cervical cancer. METHODS: The working subgroup of
      the JCOG Radiation Therapy Study Group began developing a guideline for primary
      clinical target volume in November 2009. The group consisted of 10 radiation
      oncologists and 2 gynecologic oncologists. The process started with comparing the
      contouring on computed tomographic images of actual cervical cancer cases among
      the members. This was followed by a comprehensive literature review that included
      primary research articles and textbooks as well as information on surgical
      procedures. Extensive discussion occurred in face-to-face meetings (three
      occasions) and frequent e-mail communications until a consensus was reached.
      RESULTS: The working subgroup reached a consensus on the definition for the
      clinical target volume primary. The clinical target volume primary consists of
      the gross tumor volume, uterine cervix, uterine corpus, parametrium, vagina and
      ovaries. Definitions for these component structures were determined. Anatomical
      boundaries in all directions were defined for the parametrium. Examples
      delineating these boundaries were prepared for the posterior border of the
      parametrium for various clinical situations (i.e. central tumor bulk, degree of
      parametrial involvement). CONCLUSIONS: A consensus-based guideline defining the
      clinical target volume primary was developed for external beam radiotherapy for
      intact uterine cervical cancer. This guideline will serve as a template for
      radiotherapy protocols in future clinical trials. It may also be used in actual
      clinical practice in the setting of highly precise external beam radiotherapy,
      including intensity-modulated radiotherapy.

PMID- 21875939
TI  - A case of minimally invasive intraductal papillary mucinous carcinoma resected
      after 17-year follow-up.

PMID- 21875940
TI  - Time trends in colon, rectum and anus cancer mortality between 1955 and 2008 in
      Japan, USA and Europe based on the WHO mortality database.

PMID- 21875941
TI  - Reduced level of ribonucleotide reductase R2 subunits increases dependence on
      homologous recombination repair of cisplatin-induced DNA damage.
AB  - Ribonucleotide reductase (RNR) catalyzes the rate-limiting step in the production
      of deoxyribonucleoside triphosphates (dNTPs) required for replicative and repair
      DNA synthesis. Mammalian RNR is a heteromeric enzyme consisting primarily of R1
      and R2 subunits during the S phase of the cell cycle. We have shown previously
      that the presence of excess R2 subunits protects p53-deficient human colon cancer
      cells from cisplatin-induced DNA damage and replication stress. However, the mode
      of DNA repair influenced by changes in the level of the R2 subunit remained to be
      defined. In the present study, we demonstrated that depletion of BRCA1, an
      important factor of homologous recombination repair (HRR), preferentially
      sensitized stable R2-knockdown p53(-/-) HCT116 cells to the cytotoxicity of
      cisplatin and gamma-H2AX induction. In accord with this finding, these R2
      knockdown cells exhibited increased dependence on HRR, as evidenced by elevated
      levels of cisplatin-induced Rad51 foci and sister chromatid exchange frequency.
      Furthermore, stable knockdown of the R2 subunit also led to decreased cisplatin
      induced gap-filling synthesis in nucleotide excision repair (NER) and a reduced
      dATP level in the G(2)/M phase of the cell cycle. These results suggest that an
      increased level of the R2 subunit extends the availability of dATP in the G(2)/M
      phase to promote the repair of NER-mediated single-strand gaps that are otherwise
      converted into double-strand breaks in the subsequent S phase. We propose that
      HRR becomes important for recovery from cisplatin-DNA lesions when the
      postexcision process of NER is restrained by reduced levels of the R2 subunit and
      dATP in p53-deficient cancer cells.

PMID- 21875942
TI  - Structures of cytochrome P450 2B6 bound to 4-benzylpyridine and 4-(4
      nitrobenzyl)pyridine: insight into inhibitor binding and rearrangement of active
      site side chains.
AB  - The biochemical, biophysical, and structural analysis of the cytochrome P450 2B
      subfamily of enzymes has provided a wealth of information regarding
      conformational plasticity and substrate recognition. The recent X-ray crystal
      structure of the drug-metabolizing P450 2B6 in complex with 4-(4
      chlorophenyl)imidazole (4-CPI) yielded the first atomic view of this human
      enzyme. However, knowledge of the structural basis of P450 2B6 specificity and
      inhibition has remained limited. In this study, structures of P450 2B6 were
      determined in complex with the potent inhibitors 4-benzylpyridine (4-BP) and 4-(4
      nitrobenzyl)pyridine (4-NBP). Comparison of the present structures with the
      previous P450 2B6-4-CPI complex showed that reorientation of side chains of the
      active site residue Phe206 on the F-helix and Phe297 on the I-helix was necessary
      to accommodate the inhibitors. However, P450 2B6 does not require any major side
      chain rearrangement to bind 4-NBP compared with 4-BP, and the enzyme provides no
      hydrogen-bonding partners for the polar nitro group of 4-NBP within the
      hydrophobic active site. In addition, on the basis of these new structures,
      substitution of residue 172 with histidine as observed in the single nucleotide
      polymorphism Q172H and in P450 2B4 may contribute to a hydrogen bonding network
      connecting the E- and I-helices, thereby stabilizing active site residues on the
      I-helix. These results provide insight into the role of active site side chains
      upon inhibitor binding and indicate that the recognition of the benzylpyridines
      in the closed conformation structure of P450 2B6 is based solely on
      hydrophobicity, size, and shape.

PMID- 21875943
TI  - An iron regulatory gene signature predicts outcome in breast cancer.
AB  - Changes in iron regulation characterize the malignant state. However, the
      pathways that effect these changes and their specific impact on prognosis remain
      poorly understood. We capitalized on publicly available microarray datasets
      comprising 674 breast cancer cases to systematically investigate how expression
      of genes related to iron metabolism is linked to breast cancer prognosis. Of 61
      genes involved in iron regulation, 49% were statistically significantly
      associated with distant metastasis-free survival. Cases were divided into test
      and training cohorts, and the supervised principal component method was used to
      stratify cases into risk groups. Optimal risk stratification was achieved with a
      model comprising 16 genes, which we term the iron regulatory gene signature
      (IRGS). Multivariable analysis revealed that the IRGS contributes information not
      captured by conventional prognostic indicators (HR = 1.61; 95% confidence
      interval: 1.16-2.24; P = 0.004). The IRGS successfully stratified homogeneously
      treated patients, including ER+ patients treated with tamoxifen monotherapy, both
      with (P = 0.006) and without (P = 0.03) lymph node metastases. To test whether
      multiple pathways were embedded within the IRGS, we evaluated the performance of
      two gene dyads with known roles in iron biology in ER+ patients treated with
      tamoxifen monotherapy (n = 371). For both dyads, gene combinations that minimized
      intracellular iron content [anti-import: TFRC(Low)/HFE(High); or pro-export:
      SLC40A1 (ferroportin)(High)/HAMP(Low)] were associated with favorable prognosis
      (P < 0.005). Although the clinical utility of the IRGS will require further
      evaluation, its ability to both identify high-risk patients within traditionally
      low-risk groups and low-risk patients within high-risk groups has the potential
      to affect therapeutic decision making.

PMID- 21875944
TI  - Oral fluid and plasma cannabinoid ratios after around-the-clock controlled oral
      Delta(9)-tetrahydrocannabinol administration.
AB  - BACKGROUND: Oral fluid (OF) testing is increasingly important for drug treatment,
      workplace, and drugged-driving programs. There is interest in predicting plasma
      or whole-blood concentrations from OF concentrations; however, the relationship
      between these matrices is incompletely characterized because of few controlled
      drug-administration studies. METHODS: Ten male daily cannabis smokers received
      around-the-clock escalating 20-mg oral Delta(9)-tetrahydrocannabinol (THC,
      dronabinol) doses (40-120 mg/day) for 8 days. Plasma and OF samples were
      simultaneously collected before, during, and after dosing. OF THC, 11-hydroxy-THC
      and 11-nor-9-carboxy-THC (THCCOOH) were quantified by GC-MS at 0.5-MUg/L, 0.5
      MUg/L, and 7.5-ng/L limits of quantification (LOQs), respectively. In plasma, the
      LOQs were 0.25 MUg/L for THC and THCCOOH, and 0.5 MUg/L for 11-hydroxy-THC.
      RESULTS: Despite multiple oral THC administrations each day and increasing plasma
      THC concentrations, OF THC concentrations generally decreased over time,
      reflecting primarily previously self-administered smoked cannabis. The logarithms
      of the THC concentrations in oral fluid and plasma were not significantly
      correlated (r = -0.10; P = 0.065). The OF and plasma THCCOOH concentrations,
      albeit with 1000-fold higher concentrations in plasma, increased throughout
      dosing. The logarithms of OF and plasma THCCOOH concentrations were significantly
      correlated (r = 0.63; P < 0.001), although there was high interindividual
      variation. A high OF/plasma THC ratio and a high OF THC/THCCOOH ratio indicated
      recent cannabis smoking. CONCLUSIONS: OF monitoring does not reliably detect oral
      dronabinol intake. The time courses of THC and THCCOOH concentrations in plasma
      and OF were different after repeated oral THC doses, and high interindividual
      variation was observed. For these reasons, OF cannabinoid concentrations cannot
      predict concurrent plasma concentrations.

PMID- 21875945
TI  - Flo11p, drug efflux pumps, and the extracellular matrix cooperate to form biofilm
      yeast colonies.
AB  - Much like other microorganisms, wild yeasts preferentially form surface
      associated communities, such as biofilms and colonies, that are well protected
      against hostile environments and, when growing as pathogens, against the host
      immune system. However, the molecular mechanisms underlying the spatiotemporal
      development and environmental resistance of biofilms and colonies remain largely
      unknown. In this paper, we show that a biofilm yeast colony is a finely tuned,
      complex multicellular organism in which specialized cells jointly execute
      multiple protection strategies. These include a Pdr1p-regulated mechanism whereby
      multidrug resistance transporters Pdr5p and Snq2p expel external compounds solely
      within the surface cell layers as well as developmentally regulated production by
      internal cells of a selectively permeable extracellular matrix. The two
      mechanisms act in concert during colony development, allowing growth of new cell
      generations in a well-protected internal cavity of the colony. Colony
      architecture is strengthened by intercellular fiber connections.

PMID- 21875946
TI  - Mindbomb 1, an E3 ubiquitin ligase, forms a complex with RYK to activate Wnt/beta
      catenin signaling.
AB  - Receptor-like tyrosine kinase (RYK) functions as a transmembrane receptor for the
      Wnt family of secreted protein ligands. Although RYK undergoes endocytosis in
      response to Wnt, the mechanisms that regulate its internalization and concomitant
      activation of Wnt signaling are unknown. We discovered that RYK both physically
      and functionally interacts with the E3 ubiquitin ligase Mindbomb 1 (MIB1).
      Overexpression of MIB1 promotes the ubiquitination of RYK and reduces its steady
      state levels at the plasma membrane. Moreover, we show that MIB1 is sufficient to
      activate Wnt/beta-catenin (CTNNB1) signaling and that this activity depends on
      endogenous RYK. Conversely, in loss-of-function studies, both RYK and MIB1 are
      required for Wnt-3A-mediated activation of CTNNB1. Finally, we identify the
      Caenorhabditis elegans orthologue of MIB1 and demonstrate a genetic interaction
      between ceMIB and lin-18/RYK in vulva development. These findings provide
      insights into the mechanisms of Wnt/RYK signaling and point to novel targets for
      the modulation of Wnt signaling.

PMID- 21875947
TI  - Epigenetic displacement of HP1 from heterochromatin by HIV-1 Vpr causes premature
      sister chromatid separation.
AB  - Although pericentromeric heterochromatin is essential for chromosome segregation,
      its role in humans remains controversial. Dissecting the function of HIV-1
      encoded Vpr, we unraveled important properties of heterochromatin during
      chromosome segregation. In Vpr-expressing cells, hRad21, hSgo1, and hMis12, which
      are crucial for proper chromosome segregation, were displaced from the
      centromeres of mitotic chromosomes, resulting in premature chromatid separation
      (PCS). Interestingly, Vpr displaced heterochromatin protein 1-alpha (HP1-alpha)
      and HP1-gamma from chromatin. RNA interference (RNAi) experiments revealed that
      down-regulation of HP1-alpha and/or HP1-gamma induced PCS, concomitant with the
      displacement of hRad21. Notably, Vpr stimulated the acetylation of histone H3,
      whereas p300 RNAi attenuated the Vpr-induced displacement of HP1-alpha and PCS.
      Furthermore, Vpr bound to p300 that was present in insoluble regions of the
      nucleus, suggesting that Vpr aberrantly recruits the histone acetyltransferase
      activity of p300 to chromatin, displaces HP1-alpha, and causes chromatid cohesion
      defects. Our study reveals for the first time centromere cohesion impairment
      resulting from epigenetic disruption of higher-order structures of
      heterochromatin by a viral pathogen.

PMID- 21875948
TI  - GCC185 plays independent roles in Golgi structure maintenance and AP-1-mediated
      vesicle tethering.
AB  - GCC185 is a long coiled-coil protein localized to the trans-Golgi network (TGN)
      that functions in maintaining Golgi structure and tethering mannose 6-phosphate
      receptor (MPR)-containing transport vesicles en route to the Golgi. We report the
      identification of two distinct domains of GCC185 needed either for Golgi
      structure maintenance or transport vesicle tethering, demonstrating the
      independence of these two functions. The domain needed for vesicle tethering
      binds to the clathrin adaptor AP-1, and cells depleted of GCC185 accumulate MPRs
      in transport vesicles that are AP-1 decorated. This study supports a previously
      proposed role of AP-1 in retrograde transport of MPRs from late endosomes to the
      Golgi and indicates that docking may involve the interaction of vesicle
      associated AP-1 protein with the TGN-associated tethering protein GCC185.

PMID- 21875949
TI  - Ginseng (Panax quinquefolius) attenuates leptin-induced cardiac hypertrophy
      through inhibition of p115Rho guanine nucleotide exchange factor-RhoA/Rho
      associated, coiled-coil containing protein kinase-dependent mitogen-activated
      protein kinase pathway activation.
AB  - Leptin is a 16-kDa peptide primarily derived from white adipocytes and is
      typically elevated in plasma of obese individuals. Although leptin plays a
      critical role in appetite regulation, leptin receptors have been identified in
      numerous tissues including the heart and have been shown to directly mediate
      cardiac hypertrophy through RhoA/ROCK (Ras homolog gene family, member A/Rho
      associated, coiled-coil containing protein kinase)-dependent p38 mitogen
      activated protein kinase (MAPK) activation; however, the basis for RhoA
      stimulation is unknown. Rho guanine nucleotide exchange factors (GEFs) catalyze
      the exchange of GDP for GTP resulting in Rho activation and may be the potential
      upstream factors mediating leptin-induced RhoA activation and therefore a
      potential target for inhibition. We investigated the effects of North American
      ginseng (Panax quinquefolius), reported to reduce cardiac hypertrophy, on
      RhoA/ROCK and MAPK activation in ventricular cardiomyocytes exposed to leptin (50
      ng/ml) and the possible role of p115RhoGEF and p63RhoGEF in these responses.
      Leptin produced a robust hypertrophic response that was associated with RhoA/ROCK
      activation resulting in a significant increase in cofilin-2 phosphorylation and
      actin polymerization, the latter evidenced by a reduction in the G/F actin ratio.
      These effects were prevented by ginseng (10 MUg/ml). The stimulation of RhoA/ROCK
      by leptin was associated with significantly increased p115RhoGEF gene and protein
      expression and exchange activity, all of which were completely prevented by
      ginseng. The ability of ginseng to prevent leptin-induced activation of RhoA/ROCK
      was further associated with diminished p38 MAPK activation and nuclear
      translocation. These results demonstrate a potent inhibitory effect of ginseng
      against leptin-induced cardiac hypertrophy, an effect associated with prevention
      of p115RhoGEF-RhoA/ROCK-dependent p38 MAPK activation.

PMID- 21875950
TI  - Acute oxycodone induces the pro-emetic pica response in rats.
AB  - Oxycodone, a semisynthetic opioid analgesic, is frequently prescribed for the
      management of pain. Side effects of nausea and emesis affect patient compliance
      and limit its therapeutic use. The present study established that an
      antinociceptive dose of oxycodone (15 mg/kg; oral) induces the pica response. We
      found sex differences in the temporal course of pica, with females having a
      longer duration. Opioid receptors mediated the pica response, as 1.0 mg/kg
      naloxone transiently attenuated and 2.0 mg/kg naloxone blocked pica. A kappa
      selective antagonist failed to block the response, suggesting mediation by MU
      opioid receptor. For further validation, we used the well established kaolin
      intake model to assess pica with the chemotherapeutic drug cisplatin as a
      positive control. Oxycodone and cisplatin significantly increased kaolin intake 4
      to 7-fold, and the wet weight of stomach was elevated 2- to 3-fold. To examine
      the underlying neural circuitry, we investigated c-fos activation in the area
      postrema and nucleus of solitary tract (NTS). Oxycodone treatment significantly
      increased the number of c-fos-positive neurons in the area postrema and NTS
      compared with water controls. As expected, cisplatin also increased the number of
      c-fos-positive cells in these regions. In the area postrema, the oxycodone effect
      was greater than cisplatin, especially at 2 h. These results indicate that an
      antinociceptive dose of oxycodone is associated with the expression of pica, a
      pro-emetic response.

PMID- 21875951
TI  - How to aggregate health? Separability and the effect of framing.
AB  - BACKGROUND: Unweighted summation or quality-adjusted life year (QALY)
      utilitarianism is the most common way to aggregate health benefits in a cost
      effectiveness analysis. A key qualitative principle underlying QALY
      utilitarianism is separability: those individuals unaffected by a policy choice
      should not influence the policy choice. Separability also underlies several of
      the alternatives for QALY utilitarianism that have been proposed. OBJECTIVES: To
      test separability and to test whether the support for separability is affected by
      the framing of the choice questions. METHODS: In 2 experiments, 345 student
      subjects (162 in the first experiment, and 183 in the second experiment) were
      asked to select 1 of 2 possible treatments, with each treatment resulting in a
      different distribution of health across individuals. The only aspect that varied
      across choice questions was the state of the patients whose health was unaffected
      by the act of choosing a policy. In each experiment, we used 2 frames. In the
      implicit frame, it was implied but not plainly expressed what outcomes the
      treatments had in common. In the explicit frame, common outcomes of the 2
      treatments were directly stated. The 2 experiments differed in the way the
      explicit frame was presented (verbal v. numerical). RESULTS: The support for
      separability was significantly greater in the explicit frame. The proportion of
      violations in the implicit frame was 44% in Experiment 1 and 31% in Experiment 2,
      while in the explicit frame, the proportion of violations was 28% in Experiment 1
      and 8% in Experiment 2. CONCLUSIONS: Framing affected the support for
      separability, raising issues as to whether it is possible to achieve a canonical
      representation of social choices.

PMID- 21875952
TI  - Excretion, metabolism, and pharmacokinetics of CP-945,598, a selective
      cannabinoid receptor antagonist, in rats, mice, and dogs.
AB  - 1-(8-(2-Chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl)-4-(ethylamino)piperidine
      4-carboxamide (CP-945,598) is an orally active antagonist of the cannabinoid CB-1
      receptor that progressed into phase 3 human clinical trials for the treatment of
      obesity. In this study, we investigated the metabolic fate and disposition of CP
      945,598 in rats, Tg-RasH2 mice, and dogs after oral administration of a single
      dose of [(14)C]CP-945,598. Total mean recoveries of the radioactive dose were
      97.7, 97.8, and 99.3% from mice, rats, and dogs, respectively. The major route of
      excretion in all three species was via the feces, but on the basis of separate
      studies in bile duct-cannulated rats and dogs, this probably reflects excretion
      in bile rather than incomplete absorption. CP-945,598 underwent extensive
      metabolism in all three species, because no unchanged parent compound was
      detected in the urine across species. The primary metabolic pathway of CP-945,598
      involved N-deethylation to form an N-desethyl metabolite (M1). M1 was
      subsequently metabolized by amide hydrolysis, oxidation, and ribose conjugation
      to numerous novel and unusual metabolites. The major circulating and excretory
      metabolites were species-dependent; however, several common metabolites were
      observed in more than one species. In addition to parent compound, M1, M3, M4,
      and M5 in rats, M1, M3, and M4 in mice, and M1 and M2 in dogs were identified as
      the major circulating metabolites. Gender-related differences were also apparent
      in the quantitative and qualitative nature of the metabolites in rats. An
      unprecedented metabolite, M4, formed by deamidation of M1 or M3 (N-hydroxy-M1),
      but not by decarboxylation of M2, was identified in all species. M4 was
      nonenzymatically converted to M5.

PMID- 21875953
TI  - A screen to identify cellular modulators of soluble levels of an amyotrophic
      lateral sclerosis (ALS)-causing mutant SOD1.
AB  - The molecular pathology of many protein misfolding, toxic gain-of-function
      diseases, such as amyotrophic lateral sclerosis (ALS), is not well understood.
      Although protein misfolding and aggregation are common themes in these diseases,
      efforts to identify cellular factors that regulate this process in an unbiased
      fashion and on a global scale have been lacking. Using an adapted version of an
      extant beta-gal-based protein solubility assay, an expression screen for cellular
      modulators of solubility of an ALS-causing mutant SOD1 was carried out in
      mammalian cells. Following fluorescence-activated cell sorting enrichment of a
      mouse spinal cord cDNA library for gene products that increased SOD1 solubility,
      high-throughput screening of the cDNA pools from this enriched fraction was
      employed to identify pools containing relevant modulators. Positive pools,
      containing approximately 10 cDNA clones each, were diluted and rescreened
      iteratively until individual clones that improved SOD1 folding/solubility were
      identified. Genes with profound effects in the solubility assay were selected for
      validation by independent biochemical assays. Six of 10 validated genes had a
      significant effect on SOD1 solubility and folding in a SOD1 promoter-driven beta
      gal assay, indicating that global screening of cellular targets using such
      protein solubility/folding assay is viable and can be adapted for other
      misfolding diseases.

PMID- 21875954
TI  - WASp-deficient B cells play a critical, cell-intrinsic role in triggering
      autoimmunity.
AB  - Patients with the immunodeficiency Wiskott-Aldrich syndrome (WAS) frequently
      develop systemic autoimmunity. Here, we demonstrate that mutation of the WAS gene
      results in B cells that are hyperresponsive to B cell receptor and Toll-like
      receptor (TLR) signals in vitro, thereby promoting a B cell-intrinsic break in
      tolerance. Whereas this defect leads to autoantibody production in WAS protein
      deficient (WASp(-/-)) mice without overt disease, chimeric mice in which only the
      B cell lineage lacks WASp exhibit severe autoimmunity characterized by
      spontaneous germinal center formation, class-switched autoantibodies, renal
      histopathology, and early mortality. Both T cell help and B cell-intrinsic TLR
      engagement play important roles in promoting disease in this model, as depletion
      with anti-CD4 antibodies or generation of chimeric mice with B cells deficient in
      both WASp and MyD88 prevented development of autoimmune disease. These data
      highlight the potentially harmful role for cell-intrinsic loss of B cell
      tolerance in the setting of normal T cell function, and may explain why WAS
      patients with mixed chimerism after stem cell transplantation often develop
      severe humoral autoimmunity.

PMID- 21875955
TI  - Notch signaling inhibits hepatocellular carcinoma following inactivation of the
      RB pathway.
AB  - Hepatocellular carcinoma (HCC) is the third cancer killer worldwide with >600,000
      deaths every year. Although the major risk factors are known, therapeutic options
      in patients remain limited in part because of our incomplete understanding of the
      cellular and molecular mechanisms influencing HCC development. Evidence indicates
      that the retinoblastoma (RB) pathway is functionally inactivated in most cases of
      HCC by genetic, epigenetic, and/or viral mechanisms. To investigate the
      functional relevance of this observation, we inactivated the RB pathway in the
      liver of adult mice by deleting the three members of the Rb (Rb1) gene family:
      Rb, p107, and p130. Rb family triple knockout mice develop liver tumors with
      histopathological features and gene expression profiles similar to human HCC. In
      this mouse model, cancer initiation is associated with the specific expansion of
      populations of liver stem/progenitor cells, indicating that the RB pathway may
      prevent HCC development by maintaining the quiescence of adult liver progenitor
      cells. In addition, we show that during tumor progression, activation of the
      Notch pathway via E2F transcription factors serves as a negative feedback
      mechanism to slow HCC growth. The level of Notch activity is also able to predict
      survival of HCC patients, suggesting novel means to diagnose and treat HCC.

PMID- 21875956
TI  - Critical role of Bcl11b in suppressor function of T regulatory cells and
      prevention of inflammatory bowel disease.
AB  - Dysregulated CD4(+) T cell responses and alterations in T regulatory cells
      (T(reg) cells) play a critical role in autoimmune diseases, including
      inflammatory bowel disease (IBD). The current study demonstrates that removal of
      Bcl11b at the double-positive stage of T cell development or only in T(reg) cells
      causes IBD because of proinflammatory cytokine-producing CD4(+) T cells
      infiltrating the colon. Provision of WT T(reg) cells prevented IBD, demonstrating
      that alterations in T(reg) cells are responsible for the disease. Furthermore,
      Bcl11b-deficient T(reg) cells had reduced suppressor activity with altered gene
      expression profiles, including reduced expression of the genes encoding Foxp3 and
      IL-10, and up-regulation of genes encoding proinflammatory cytokines.
      Additionally, the absence of Bcl11b altered the induction of Foxp3 expression and
      reduced the generation of induced T(reg) cells (iT(reg) cells) after Tgf-beta
      treatment of conventional CD4(+) T cells. Bcl11b bound to Foxp3 and IL-10
      promoters, as well as to critical conserved noncoding sequences within the Foxp3
      and IL-10 loci, and mutating the Bcl11b binding site in the Foxp3 promoter
      reduced expression of a luciferase reporter gene. These experiments demonstrate
      that Bcl11b is indispensable for T(reg) suppressor function and for maintenance
      of optimal Foxp3 and IL-10 gene expression, as well as for the induction of Foxp3
      expression in conventional CD4(+) T cells in response to Tgf-beta and generation
      of iT(reg) cells.

PMID- 21875957
TI  - Cannabinoid receptor 2 positions and retains marginal zone B cells within the
      splenic marginal zone.
AB  - Specialized B cells residing in the splenic marginal zone (MZ) continuously
      survey the blood for antigens and are important for immunity to systemic
      infections. However, the cues that uniquely attract cells to the MZ have not been
      defined. Previous work demonstrated that mice deficient in cannabinoid receptor 2
      (CB2) have decreased numbers of MZ B cells but it has been unclear whether CB2
      regulates MZ B cell development or positioning. We show that MZ B cells are
      highly responsive to the CB2 ligand 2-arachidonylglycerol (2-AG) and that CB2
      antagonism rapidly displaces small numbers of MZ B cells to the blood. Antagonism
      for longer durations depletes MZ B cells from the spleen. In mice deficient in
      sphingosine-1-phosphate receptor function, CB2 antagonism causes MZ B cell
      displacement into follicles. Moreover, CB2 overexpression is sufficient to
      position B cells to the splenic MZ. These findings establish a role for CB2 in
      guiding B cells to the MZ and in preventing their loss to the blood. As a
      consequence of their MZ B cell deficiency, CB2-deficient mice have reduced
      numbers of CD1d-high B cells. We show that CB2 deficiency results in diminished
      humoral responses to a CD1d-restricted systemic antigen.

PMID- 21875958
TI  - Sustained suppression by Foxp3+ regulatory T cells is vital for infectious
      transplantation tolerance.
AB  - A paradigm shift in immunology has been the recent discovery of regulatory T
      cells (T reg cells), of which CD4(+)Foxp3(+) cells are proven as essential to
      self-tolerance. Using transgenic B6.Foxp3(hCD2) mice to isolate and ablate
      Foxp3(+) T reg cells with an anti-hCD2 antibody, we show for the first time that
      CD4(+)Foxp3(+) cells are crucial for infectious tolerance induced by nonablative
      anti-T cell antibodies. In tolerant animals, Foxp3(+) T reg cells are constantly
      required to suppress effector T cells still capable of causing tissue damage.
      Tolerated tissue contains T cells that are capable of rejecting it, but are
      prevented from doing so by therapeutically induced Foxp3(+) T reg cells. Finally,
      Foxp3(+) cells have been confirmed as the critical missing link through which
      infectious tolerance operates in vivo. Peripherally induced Foxp3(+) cells
      sustain tolerance by converting naive T cells into the next generation of
      Foxp3(+) cells. Empowering Foxp3(+) regulatory T cells in vivo offers a tractable
      route to avoid and correct tissue immunopathology.

PMID- 21875959
TI  - Next-generation computational genetic analysis: multiple complement alleles
      control survival after Candida albicans infection.
AB  - Candida albicans is a fungal pathogen that causes severe disseminated infections
      that can be lethal in immunocompromised patients. Genetic factors are known to
      alter the initial susceptibility to and severity of C. albicans infection. We
      developed a next-generation computational genetic mapping program with advanced
      features to identify genetic factors affecting survival in a murine genetic model
      of hematogenous C. albicans infection. This computational tool was used to
      analyze the median survival data after inbred mouse strains were infected with C.
      albicans, which provides a useful experimental model for identification of host
      susceptibility factors. The computational analysis indicated that genetic
      variation within early classical complement pathway components (C1q, C1r, and
      C1s) could affect survival. Consistent with the computational results, serum C1
      binding to this pathogen was strongly affected by C1rs alleles, as was survival
      of chromosome substitution strains. These results led to a combinatorial,
      conditional genetic model, involving an interaction between C5 and C1r/s alleles,
      which accurately predicted survival after infection. Beyond applicability to
      infectious disease, this information could increase our understanding of the
      genetic factors affecting susceptibility to autoimmune and neurodegenerative
      diseases.

PMID- 21875960
TI  - Necessary and sufficient role for T helper cells to prevent fungal dissemination
      in allergic lung disease.
AB  - Mucosal immune responses to fungal infection range from T helper type 2 (Th2)
      cell-directed allergic inflammation to Th1-predominant neutrophilic inflammation,
      but the mechanisms directing these divergent mucosal immune outcomes and the role
      of T cells in host defense against mucosal fungal infections are not known. Here
      we examined the mouse mucosal immune responses to 12 filamentous environmental
      fungal species over a broad range of exposure doses and determined the
      requirement of T cells for host defense. For all tested fungi, low-grade conidium
      exposures induced Th2- and eosinophil-predominant allergic lung disease, whereas
      higher exposures led to rapid conversion to neutrophil- and Th1 cell-predominant
      inflammation, a phenomenon we term immune phenotype switching. All fungal
      exposure doses were further linked to the secretion of interleukin-17A (IL-17A).
      Fungal infections with Curvularia lunata and Aspergillus fumigatus were typically
      confined to the airway during allergic inflammation but became locally invasive
      and disseminated to the brain at higher conidium challenge doses, in association
      with predominant Th1 responses. Fungal dissemination occurred at relatively low
      challenge doses with the conidia of Aspergillus fumigatus administered to
      recombinase activating gene 1 (Rag-1)-deficient mice, which lack B and T cells,
      but B cell-deficient MUMT mice and T helper cell-reconstituted Rag-1-deficient
      mice were comparable to wild-type mice in preventing fungal dissemination. Our
      findings demonstrate that Th2 cell-predominant allergic responses followed by
      immune phenotype switching and fungal dissemination are highly predictable
      outcomes with progressive fungal infectious burdens and that T helper cell
      responses are protective against lethal fungal dissemination.

PMID- 21875961
TI  - Filarial lymphatic pathology reflects augmented toll-like receptor-mediated,
      mitogen-activated protein kinase-mediated proinflammatory cytokine production.
AB  - Lymphatic filariasis can be associated with the development of serious pathology
      in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected
      patients. Toll-like receptors (TLRs) are thought to play a major role in the
      development of filarial pathology. To elucidate the role of TLRs in the
      development of lymphatic pathology, we examined cytokine responses to different
      Toll ligands in patients with chronic lymphatic pathology (CP), infected patients
      with subclinical pathology (INF), and uninfected, endemic-normal (EN)
      individuals. TLR2, -7, and -9 ligands induced significantly elevated production
      of Th1 and other proinflammatory cytokines in CP patients in comparison to both
      INF and EN patients. TLR adaptor expression was not significantly different among
      the groups; however, both TLR2 and TLR9 ligands induced significantly higher
      levels of phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2)
      and p38 mitogen-activated protein (MAP) kinases (MAPK) as well as increased
      activation of NF-kappaB in CP individuals. Pharmacologic inhibition of both
      ERK1/2 and p38 MAP kinase pathways resulted in significantly diminished
      production of proinflammatory cytokines in CP individuals. Our data, therefore,
      strongly suggest an important role for TLR2- and TLR9-mediated proinflammatory
      cytokine induction and activation of both the MAPK and NF-kappaB pathways in the
      development of pathology in human lymphatic filariasis.

PMID- 21875962
TI  - LuxS mediates iron-dependent biofilm formation, competence, and fratricide in
      Streptococcus pneumoniae.
AB  - During infection, Streptococcus pneumoniae exists mainly in sessile biofilms
      rather than in planktonic form, except during sepsis. The capacity to form
      biofilms is believed to be important for nasopharyngeal colonization as well as
      disease pathogenesis, but relatively little is known about the regulation of this
      process. Here, we investigated the effect of exogenous iron [Fe(III)] as well as
      the role of luxS (encoding S-ribosylhomocysteine lyase) on biofilm formation by
      S. pneumoniae D39. Fe(III) strongly enhanced biofilm formation at concentrations
      of >=50 MUM, while Fe(III) chelation with deferoxamine was inhibitory.
      Importantly, Fe(III) also upregulated the expression of luxS in wild-type D39. A
      luxS-deficient mutant (D39luxS) failed to form a biofilm, even with Fe(III)
      supplementation, whereas a derivative overexpressing luxS (D39luxS+) exhibited
      enhanced biofilm formation capacity and could form a biofilm without added
      Fe(III). D39luxS exhibited reduced expression of the major Fe(III) transporter
      PiuA, and the cellular [Fe(III)] was significantly lower than that in D39; in
      contrast, D39luxS+ had a significantly higher cellular [Fe(III)] than the wild
      type. The release of extracellular DNA, which is an important component of the
      biofilm matrix, also was directly related to luxS expression. Similarly, genetic
      competence, as measured by transformation frequency as well as the expression of
      competence genes comD, comX, comW, cglA, and dltA and the murein hydrolase cbpD,
      which is associated with fratricide-dependent DNA release, all were directly
      related to luxS expression levels and were further upregulated by Fe(III).
      Moreover, mutagenesis of cbpD blocked biofilm formation. We propose that
      competence, fratricide, and biofilm formation are closely linked in pneumococci,
      and that luxS is a central regulator of these processes. We also propose that the
      stimulatory effects of Fe(III) on all of these parameters are due to the
      upregulation of luxS expression, and that LuxS provides for a positive Fe(III)
      dependent amplification loop by increasing iron uptake.

PMID- 21875963
TI  - Protective role of naturally occurring interleukin-17A-producing gammadelta T
      cells in the lung at the early stage of systemic candidiasis in mice.
AB  - Interleukin-17A (IL-17A)-producing gammadelta T cells differentiate in the fetal
      thymus and reside in the peripheral tissues, such as the lungs of naive adult
      mice. We show here that naturally occurring gammadelta T cells play a protective
      role in the lung at a very early stage after systemic infection with Candida
      albicans. Selective depletion of neutrophils by in vivo administration of anti
      Ly6G monoclonal antibody (MAb) impaired fungal clearance more prominently in the
      lung than in the kidney 24 h after intravenous infection with C. albicans. Rapid
      and transient production of IL-23 was detected in the lung at 12 h, preceding IL
      17A production and the influx of neutrophils, which reached a peak at 24 h after
      infection. IL-17A knockout (KO) mice showed reduced infiltration of neutrophils
      concurrently with impaired fungal clearance in the lung after infection. The
      major source of IL-17A was the gammadelta T cell population in the lung, and
      Cdelta KO mice showed little IL-17A production and reduced neutrophil
      infiltration after infection. Early IL-23 production in a TLR2/MyD88-dependent
      manner and IL-23-triggered tyrosine kinase 2 (Tyk2) signaling were essential for
      IL-17A production by gammadelta T cells. Thus, our study demonstrated a novel
      role of naturally occurring IL-17A-producing gammadelta T cells in the first line
      of host defense against C. albicans infection.

PMID- 21875964
TI  - The deubiquitinase activity of the Salmonella pathogenicity island 2 effector,
      SseL, prevents accumulation of cellular lipid droplets.
AB  - To cause disease, Salmonella enterica serovar Typhimurium requires two type III
      secretion systems that are encoded by Salmonella pathogenicity islands 1 and 2
      (SPI-1 and -2). These secretion systems serve to deliver specialized proteins
      (effectors) into the host cell cytosol. While the importance of these effectors
      to promote colonization and replication within the host has been established, the
      specific roles of individual secreted effectors in the disease process are not
      well understood. In this study, we used an in vivo gallbladder epithelial cell
      infection model to study the function of the SPI-2-encoded type III effector,
      SseL. The deletion of the sseL gene resulted in bacterial filamentation and
      elongation and the unusual localization of Salmonella within infected epithelial
      cells. Infection with the DeltasseL strain also caused dramatic changes in host
      cell lipid metabolism and led to the massive accumulation of lipid droplets in
      infected cells. This phenotype was directly attributable to the deubiquitinase
      activity of SseL, as a Salmonella strain carrying a single point mutation in the
      catalytic cysteine also resulted in extensive lipid droplet accumulation. The
      excessive buildup of lipids due to the absence of a functional sseL gene also was
      observed in murine livers during S. Typhimurium infection. These results suggest
      that SseL alters host lipid metabolism in infected epithelial cells by modifying
      the ubiquitination patterns of cellular targets.

PMID- 21875965
TI  - Comparative analysis of EspF variants in inhibition of Escherichia coli
      phagocytosis by macrophages and inhibition of E. coli translocation through human
      and bovine-derived M cells.
AB  - The EspF protein is secreted by the type III secretion system of enteropathogenic
      and enterohemorrhagic Escherichia coli (EPEC and EHEC, respectively). EspF
      sequences differ between EHEC O157:H7, EHEC O26:H11, and EPEC O127:H6 in terms of
      the number of SH3-binding polyproline-rich repeats and specific residues in these
      regions, as well as residues in the amino domain involved in cellular
      localization. EspF(O127) is important for the inhibition of phagocytosis by EPEC
      and also limits EPEC translocation through antigen-sampling cells (M cells).
      EspF(O127) has been shown to have effects on cellular organelle function and
      interacts with several host proteins, including N-WASP and sorting nexin 9
      (SNX9). In this study, we compared the capacities of different espF alleles to
      inhibit (i) bacterial phagocytosis by macrophages, (ii) translocation through an
      M-cell coculture system, and (iii) uptake by and translocation through cultured
      bovine epithelial cells. The espF gene from E. coli serotype O157 (espF(O157))
      allele was significantly less effective at inhibiting phagocytosis and also had
      reduced capacity to inhibit E. coli translocation through a human-derived in
      vitro M-cell coculture system in comparison to espF(O127) and espF(O26). In
      contrast, espF(O157) was the most effective allele at restricting bacterial
      uptake into and translocation through primary epithelial cells cultured from the
      bovine terminal rectum, the predominant colonization site of EHEC O157 in cattle
      and a site containing M-like cells. Although LUMIER binding assays demonstrated
      differences in the interactions of the EspF variants with SNX9 and N-WASP, we
      propose that other, as-yet-uncharacterized interactions contribute to the host
      based variation in EspF activity demonstrated here.

PMID- 21875966
TI  - The Photobacterium damselae subsp. damselae hemolysins damselysin and HlyA are
      encoded within a new virulence plasmid.
AB  - Photobacterium damselae subsp. damselae (formerly Vibrio damsela) is a marine
      bacterium that causes infections and fatal disease in a wide range of marine
      animals and in humans. Highly hemolytic strains produce damselysin (Dly), a
      cytolysin encoded by the dly gene that is lethal for mice and has hemolytic
      activity. We found that Dly is encoded in the highly hemolytic strain RM-71
      within a 153,429-bp conjugative plasmid that we dubbed pPHDD1. In addition to
      Dly, pPHDD1 also encodes a homologue of the pore-forming toxin HlyA. We found a
      direct correlation between presence of pPHDD1 and a strong hemolytic phenotype in
      a collection of P. damselae subsp. damselae isolates. Hemolysis was strongly
      reduced in a double dly hlyA mutant, demonstrating the role of the two pPHDD1
      encoded genes in hemolysis. Interestingly, although single hlyA and dly mutants
      showed different levels of hemolysis reduction depending on the erythrocyte
      source, hemolysis was not abolished in any of the single mutants, suggesting that
      the hemolytic phenotype is the result of the additive effect of Dly and HlyA. We
      found that pPHDD1-encoded dly and hlyA genes are necessary for full virulence for
      mice and fish. Our results suggest that pPHDD1 can be considered as a driving
      force for the emergence of a highly hemolytic lineage of P. damselae subsp.
      damselae.

PMID- 21875968
TI  - Three new teosintes (Zea spp., Poaceae) from Mexico.
AB  - PREMISE OF THE STUDY: Teosinte species are the closest relatives of maize and
      represent an important but increasingly rare genetic resource for maize
      improvement and the study of evolution by domestication. Three morphologically
      and ecologically distinct teosinte populations were recently discovered in
      Mexico. The taxonomic status of these rare and endangered populations was
      investigated by detailed comparisons to previously characterized wild Zea
      species. * METHODS: Three new teosinte populations were compared to known
      teosinte taxa on the basis of morphological, ecogeographic, cytological, and
      molecular characteristics. Phenetic and phylogenetic analyses were performed
      using morphological and molecular data, respectively. * KEY RESULTS: The newly
      discovered populations are distinct from each other and from other Zea species to
      represent three new entities based on their unique combinations of morphological,
      ecological, ploidy, and DNA markers. A perennial diploid population from Nayarit
      is distinguished by early maturing plants, and having male inflorescences with
      few tassel branches and long spikelets. A perennial tetraploid population from
      Michoacan is characterized by tall and late maturing plants, and having male
      inflorescences with many branches. An annual diploid population from Oaxaca is
      characterized by having male inflorescences with fewer branches and longer
      spikelets than those found in the sister taxa Z. luxurians and Z. nicaraguensis,
      plants with high thermal requirements, and very long seed dormancy. *
      CONCLUSIONS: Evidence from multiple independent sources suggests placement of the
      three new populations of teosinte as distinct entities within section Luxuriantes
      of the genus Zea. However, more extensive DNA marker or sequence data are
      required to resolve the taxonomy of this genus.

PMID- 21875967
TI  - Elicitation of epithelial cell-derived immune effectors by outer membrane
      vesicles of nontypeable Haemophilus influenzae.
AB  - Outer membrane vesicles (OMVs) are produced by all Gram-negative microorganisms
      studied to date. The contributions of OMVs to biological processes are diverse
      and include mediation of bacterial stress responses, selective packaging and
      secretion of virulence determinants, modulation of the host immune response, and
      contributions to biofilm formation and stability. First characterized as
      transformasomes in Haemophilus, these membranous blebs facilitate transfer of DNA
      among bacteria. Nontypeable Haemophilus influenzae (NTHI), an opportunistic
      pathogen of the upper and lower respiratory tracts, produces OMVs in vivo, but
      there is a paucity of information regarding both the composition and role of OMVs
      during NTHI colonization and pathogenesis. We demonstrated that purified NTHI
      vesicles are 20 to 200 nm in diameter and contain DNA, adhesin P5, IgA
      endopeptidase, serine protease, and heme utilization protein, suggesting a
      multifaceted role in virulence. NTHI OMVs can bind to human pharyngeal epithelial
      cells, resulting in a time- and temperature-dependent aggregation on the host
      cell surface, with subsequent internalization. OMVs colocalize with the
      endocytosis protein caveolin, indicating that internalization is mediated by
      caveolae, which are cholesterol-rich lipid raft domains. Upon interaction with
      epithelial cells, NTHI OMVs stimulate significant release of the immunomodulatory
      cytokine interleukin-8 (IL-8) as well as the antimicrobial peptide LL-37. Thus,
      we demonstrated that NTHI OMVs contain virulence-associated proteins that
      dynamically interact with and invade host epithelial cells. Beyond their ability
      to mediate DNA transfer in Haemophilus, OMV stimulation of host immunomodulatory
      cytokine and antimicrobial peptide release supports a dynamic role for
      vesiculation in NTHI pathogenesis and clinically relevant disease progression.

PMID- 21875969
TI  - An ontology of fungal subcellular traits.
AB  - * PREMISE OF THE STUDY: The Fungal Subcellular Ontology used in the Assembling
      the Fungal Tree of Life project is a taxon-wide ontology (controlled vocabulary
      for attributes) designed to clarify and integrate the broad range of subcellular
      characters and character states used in higher-level fungal systematics. As in
      the algae, cellular characters are important phylogenetic markers in kingdom
      Fungi. The Fungal Subcellular Ontology has been developed primarily to help
      researchers, especially systematists, in their search for information on
      subcellular characters across the Fungi, and it complements existing biological
      ontologies, including the Gene Ontology. * METHODS: The character and character
      state data set used in the Assembling the Fungal Tree of Life Structural and
      Biochemical Database (http://aftol.umn.edu) is the source of terms for generating
      the ontology. After the terms were accessioned and defined, they were combined in
      OBO-Edit file format, and the ontology was edited using OBO-Edit, an open source
      Java tool supported by the Gene Ontology project. * KEY RESULTS: The Fungal
      Subcellular Ontology covers both model and nonmodel fungi in great detail and is
      downloadable in OBO-Edit format at website
      http://aftol.umn.edu/ontology/fungal_subcellular.obo. * CONCLUSIONS: The ontology
      provides a controlled vocabulary of fungal subcellular terms and functions as an
      operating framework for the Assembling the Fungal Tree of Life Structural and
      Biochemical Database. An ontology-based design enhances reuse of data deposited
      in the Structural and Biochemical Database from other independent biological and
      genetic databases. Data integration approaches that advance access to data from
      the diversity of biological databases are imperative as interdisciplinary
      research gains importance. In this sense, the Fungal Subcellular Ontology becomes
      highly relevant to mycologists as well as nonmycologists because fungi interact
      actively as symbionts and parasites or passively with many other life forms.

PMID- 21875970
TI  - Comparative anatomical and developmental analysis of dry and fleshy fruits of
      Solanaceae.
AB  - PREMISE OF THE STUDY: An anatomical examination of dry and fleshy fruits within
      the Solanaceae was carried out to identify comparable stages throughout
      development as well as features exclusive to each type of fruit. We studied fruit
      development of Nicotiana and Petunia, which have the plesiomorphic capsular
      fruit; Solanum and Iochroma, characterized by a derived fleshy berry; Cestrum, an
      independent origin of a fleshy fruit; and Datura, a reversion to a dry fruit. *
      METHODS: Pre- and postanthesis carpels and fruits of all species were collected,
      sectioned, stained, and examined using light microscopy. * KEY RESULTS:
      Comparable stages of carpel and fruit development were identified in all species.
      Furthermore, anatomical and developmental features were identified that
      characterize capsules in Solanaceae, including lack of increase in the number of
      pericarp cell layers, formation of a sclerified endocarp, and elongation of the
      epidermal cells of the placenta. Pericarps of fleshy fruits of the Solanoideae
      are characterized by abundant collenchyma, an increase in the number of cell
      layers, and a parenchymatous endocarp often expanding into the locules.
      Anatomical data show that early developmental stages of the fruit of Cestrum, a
      berry, are similar to the capsular fruits of Petunia and Nicotiana; similarly,
      Datura, one of the few capsular members of the Solanoideae, shares several
      anatomical features with closely related berried taxa. * CONCLUSIONS:
      Ontogenetically, all fleshy or all dry fruits do not necessarily share a common
      developmental ground plan. Independent evolution of fleshiness, sclerification,
      dryness, and dehiscence are discussed in a phylogenetic context.

PMID- 21875971
TI  - Characterization of 12 microsatellite loci for Hypochaeris chillensis
      (Asteraceae) and cross-amplification in related species.
AB  - PREMISE OF THE STUDY: Hypochaeris is considered a biological model to understand
      evolutionary processes in the vascular flora of South America, particularly from
      the temperate portion of the continent. We report the development and
      characterization of microsatellite markers for H. chillensis to assess the
      genetic variability and patterns of population structure of the species. *
      METHODS AND RESULTS: Twelve microsatellite primers were isolated using a CT- and
      GT-enriched genomic library. PCR amplification detected one to five alleles, with
      2.91 alleles per locus on average. Tested for cross-amplification, all primer
      pairs were successfully amplified in 10 South American species and in the
      putative ancestor of the group, H. angustifolia. * CONCLUSIONS: The
      microsatellites can be used to assess genetic diversity and population structure
      of H. chillensis. Application in other species will focus on the elucidation of
      adaptive radiation of the genus in South America.

PMID- 21875972
TI  - Genetic consequences of seed banks in the perennial herb Arabidopsis lyrata
      subsp. petraea (Brassicaceae).
AB  - PREMISE OF THE STUDY: Seed banks may increase the effective population size
      (N(e)) of plants as a result of elevated coalescence times for alleles residing
      in the populations. This has been empirically demonstrated in populations of the
      annual Arabidopsis thaliana, whereas comparable data for perennial species are
      currently lacking. We studied the contribution of seed banks to effective sizes
      of natural populations of the self-incompatible, perennial Arabidopsis lyrata
      subsp. petraea, a close relative of A. thaliana. * METHODS: Fourteen populations
      of A. lyrata collected throughout the Norwegian distribution range were analyzed
      using microsatellite markers. * KEY RESULTS: The genetic composition of seed-bank
      and aboveground cohorts was found to be highly similar, with little genetic
      differentiation between cohorts in most populations. However, the proportion of
      private alleles was higher in aboveground than in seed-bank cohorts. The presence
      of seed banks significantly increased total N(e), but the contribution from seed
      banks to overall N(e) were lower than the contribution from aboveground cohorts
      in most populations. Estimated historical N(e) values, reflecting the effective
      sizes of populations throughout the history of the species, were considerably
      higher than estimates of contemporary N(e), reflecting number of reproducing
      individuals within the past few generations. * CONCLUSIONS: The results show that
      the seed bank contributes to total N(e) in the perennial herb A. lyrata. However,
      the contribution is similar to or lower than that of the above-ground fraction of
      the population and markedly weaker than that previously documented in the annual
      A. thaliana.

PMID- 21875973
TI  - Congruence between geographic range distribution and local competitive ability of
      two Lupinus species.
AB  - PREMISE OF THE STUDY: In spite of its relevance, we lack rigorous evidence on
      whether widespread species are superior local competitors compared with
      coexisting narrowly distributed congeners. We ran a competition experiment
      between two lupins that coexist at their shared geographic range: Lupinus
      angustifolius L. (widespread) and L. gredensis Gandoger (narrow endemic). *
      METHODS: We set up mixed and monospecific populations of the two species,
      monitored survival and fecundity until the death of the whole cohorts, and
      measured variables of putative relevance to the competition process. We used
      aster modeling to address lifetime individual fitness and generalized linear
      models to assess the effect of species, type of competition, and competition
      environment on a suite of competition indices. * KEY RESULTS: Lupinus
      angustifolius showed higher fitness and exerted a stronger competitive effect on
      its heterospecific neighbors. This occurred through higher fecundity late in the
      season rather than through differential survival at earlier stages. *
      CONCLUSIONS: This is the first evidence of lifetime superior competitive
      potential of a widespread species over a narrow endemic congener. This
      competitive response might scale up to the geographic distribution range and may
      partially explain the limited distribution of the narrow endemic. Extension to
      other carefully selected study cases and more in-depth field experiments may help
      to assess the generality of this pattern and understand how local processes
      translate into geographic patterns.

PMID- 21875974
TI  - Microsatellite markers for Dayaoshania cotinifolia (Gesneriaceae), a critically
      endangered perennial herb.
AB  - PREMISE OF THE STUDY: Microsatellite primers were developed for the critically
      endangered species Dayaoshania cotinifolia (Gesneriaceae) to evaluate population
      genetic diversity and detect population history. * METHODS AND RESULTS: In our
      study, 15 primer sets were developed using an enriched genomic library. These are
      the first microsatellite loci developed for this genus. Genetic diversity was
      measured using 40 individuals. The number of alleles per locus ranged from one to
      six, and the incidence of observed heterozygosities was 0.365 and 0.410 in two
      populations. * CONCLUSIONS: The described markers will be useful in future
      population genetics studies of this critically endangered species.

PMID- 21875975
TI  - Phylogenetics of the Chamaesyce clade (Euphorbia, Euphorbiaceae): reticulate
      evolution and long-distance dispersal in a prominent C4 lineage.
AB  - PREMISE OF THE STUDY: The Chamaesyce clade of Euphorbia is the largest lineage
      of C(4) plants among the eudicots, with 350 species including both narrow
      endemics and cosmopolitan weeds. We sampled this group worldwide to address
      questions about subclade relationships, the origin of C(4) photosynthesis, the
      evolution of weeds, and the role of hybridization and long-distance dispersal in
      the diversification of the group. * METHODS: Two nuclear (ITS and exon 9 of
      EMB2765) and three chloroplast markers (matK, rpl16, and trnL-F) were sequenced
      for 138 ingroup and six outgroup species. Exon 9 of EMB2765 was cloned in
      accessions with >1% superimposed peaks. * KEY RESULTS: The Chamaesyce clade is
      monophyletic and consists of three major subclades [1(2,3)]: (1) the Acuta clade,
      containing three North American species with C(3) photosynthesis and C(3)-C(4)
      intermediates; (2) the Peplis clade, mostly North American and entirely C(4); and
      (3) the Hypericifolia clade, all C(4), with both New World and Old World groups.
      Incongruence between chloroplast and ITS phylogenies and divergent cloned copies
      of EMB2765 exon 9 suggest extensive hybridization, especially in the Hawaiian
      Islands radiation. * CONCLUSIONS: The Chamaesyce clade originated in warm, arid
      areas of North America, where it evolved C(4) photosynthesis. From there, it
      diversified globally with extensive reticulate evolution and frequent long
      distance dispersals. Although many species are weedy, there are numerous local
      adaptations to specific substrates and regional or island radiations, which have
      contributed to the great diversity of this group.

PMID- 21875976
TI  - Perspectives on: information coding in mammalian sensory physiology.

PMID- 21875977
TI  - Perspectives on: information and coding in mammalian sensory physiology:
      nonlinear spatial encoding by retinal ganglion cells: when 1 + 1 ? 2.

PMID- 21875979
TI  - Perspectives on: information and coding in mammalian sensory physiology: response
      kinetics of olfactory receptor neurons and the implications in olfactory coding.

PMID- 21875978
TI  - Perspectives on: information and coding in mammalian sensory physiology: probing
      mammalian touch transduction.

PMID- 21875981
TI  - Can selectivity be functionally modulated in ion channels?

PMID- 21875982
TI  - A minimalist model for ion partitioning and competition in a K+ channel
      selectivity filter.

PMID- 21875980
TI  - Perspectives on: information and coding in mammalian sensory physiology:
      inhibitory synaptic mechanisms underlying functional diversity in auditory
      cortex.

PMID- 21875983
TI  - Ion selectivity of proteins: lessons from molecular dynamics simulations on
      valinomycin.

PMID- 21875988
TI  - Bias in systematic reviews?

PMID- 21875986
TI  - Models for Golgi traffic: a critical assessment.
AB  - A variety of secretory cargoes move through the Golgi, but the pathways and
      mechanisms of this traffic are still being debated. Here, we evaluate the
      strengths and weaknesses of five current models for Golgi traffic: (1)
      anterograde vesicular transport between stable compartments, (2) cisternal
      progression/maturation, (3) cisternal progression/maturation with heterotypic
      tubular transport, (4) rapid partitioning in a mixed Golgi, and (5) stable
      compartments as cisternal progenitors. Each model is assessed for its ability to
      explain a set of key observations encompassing multiple cell types. No single
      model can easily explain all of the observations from diverse organisms. However,
      we propose that cisternal progression/maturation is the best candidate for a
      conserved core mechanism of Golgi traffic, and that some cells elaborate this
      core mechanism by means of heterotypic tubular transport between cisternae.

PMID- 21875990
TI  - Aesthetic colour performance of plastic and ceramic brackets -- an in vitro
      study.
AB  - OBJECTIVE: To evaluate the aesthetic colour performance (colour blending) of
      plastic and ceramic brackets by determining the colour changes of shade guide
      tabs before and after bracket placement. DESIGN: In vitro, laboratory study.
      MATERIALS AND METHODS: Four plastic and four ceramic brackets were investigated
      (n=5). Brackets were placed on the labial surface of the A1 and A4 tabs of a
      Vitapan classic shade guide. The colours of the areas corresponding to the
      central and inferior areas of the brackets were measured before and after bracket
      placement according to the CIELAB colour scale with a spectroradiometer. Changes
      in colour (DeltaE*(ab)) and colour coordinates (DeltaL*, Deltaa*, Deltab* and
      DeltaC*(ab)) of the tabs after bracket placement were calculated. RESULTS: Colour
      changes in the central and inferior areas were in the ranges of 5.6-11.1 and 4.3
      12.3 DeltaE*(ab) units, respectively. Changes in colour and colour coordinates
      were influenced by shade tab colour and bracket brand (P<0.05). Compared to A1
      tab, DeltaE*(ab), Deltaa*, Deltab* and DeltaC*(ab) values on A4 tab were
      significantly higher (P<0.01). The hybrid polymer bracket and glass reinforced
      plastic bracket induced the smallest colour changes in the central and inferior
      areas. CONCLUSIONS: All the investigated aesthetic brackets induced clinically
      unacceptable (DeltaE*(ab)>5.5) or perceptible (DeltaE*(ab)>2.6) colour changes
      when placed on the shade tabs. Aesthetic colour performance of brackets on the
      less chromatic and lighter tab was better than that on the more chromatic and
      dark tab. High translucency of bracket alone did not lead to better aesthetic
      colour performance.

PMID- 21875985
TI  - Protein folding and quality control in the ER.
AB  - The endoplasmic reticulum (ER) uses an elaborate surveillance system called the
      ER quality control (ERQC) system. The ERQC facilitates folding and modification
      of secretory and membrane proteins and eliminates terminally misfolded
      polypeptides through ER-associated degradation (ERAD) or autophagic degradation.
      This mechanism of ER protein surveillance is closely linked to redox and calcium
      homeostasis in the ER, whose balance is presumed to be regulated by a specific
      cellular compartment. The potential to modulate proteostasis and metabolism with
      chemical compounds or targeted siRNAs may offer an ideal option for the treatment
      of disease.

PMID- 21875987
TI  - Calcium signaling in cardiac myocytes.
AB  - Calcium (Ca(2+)) is a critical regulator of cardiac myocyte function.
      Principally, Ca(2+) is the link between the electrical signals that pervade the
      heart and contraction of the myocytes to propel blood. In addition, Ca(2+)
      controls numerous other myocyte activities, including gene transcription. Cardiac
      Ca(2+) signaling essentially relies on a few critical molecular players-
      ryanodine receptors, voltage-operated Ca(2+) channels, and Ca(2+)
      pumps/transporters. These moieties are responsible for generating Ca(2+) signals
      upon cellular depolarization, recovery of Ca(2+) signals following cellular
      contraction, and setting basal conditions. Whereas these are the central players
      underlying cardiac Ca(2+) fluxes, networks of signaling mechanisms and accessory
      proteins impart complex regulation on cardiac Ca(2+) signals. Subtle changes in
      components of the cardiac Ca(2+) signaling machinery, albeit through mutation,
      disease, or chronic alteration of hemodynamic demand, can have profound
      consequences for the function and phenotype of myocytes. Here, we discuss
      mechanisms underlying Ca(2+) signaling in ventricular and atrial myocytes. In
      particular, we describe the roles and regulation of key participants involved in
      Ca(2+) signal generation and reversal.

PMID- 21875991
TI  - Early correction of anterior crossbites: a systematic review.
AB  - OBJECTIVES: To identify the appropriate treatment for the correction of anterior
      crossbite. DESIGN: Systematic review. DATA SOURCE: A search strategy was
      developed along with inclusion criteria and run in Scopus, Medline, Cochrane
      Library, EMBASE and psychINFO databases. SELECTION CRITERIA: Children in the
      primary or mixed dentition with an anterior crossbite affecting one or more
      incisors, and no underlying skeletal class III discrepancy. DATA SELECTION AND
      EXTRACTION: All potential articles were checked against the inclusion criteria
      independently, and in duplicate by two investigators. Reference lists were
      checked for relevance and possible inclusion. Manual data extraction was carried
      out using a standardized format and agreed by the two investigators. OUTCOMES:
      Time taken to correct the crossbite and treatment duration. DATA SYNTHESIS: The
      data were arranged by type of study and further subdivided by treatment type.
      RESULTS: A total of 499 articles were identified following electronic and hand
      searching and checking reference lists. Following examination of titles,
      abstracts and, where applicable full articles, 46 articles were included. Owing
      to the low levels of evidence, no statistical methods were employed. CONCLUSION:
      This review has highlighted the lack of high quality evidence for the management
      of anterior crossbites in children. Although the level of evidence is low, there
      is similarity in the length of time it took to successfully treat anterior
      crossbites using similar treatment modalities. High level studies are required
      before definitive conclusions can be made.

PMID- 21875984
TI  - The thrombospondins.
AB  - Thrombospondins are evolutionarily conserved, calcium-binding glycoproteins that
      undergo transient or longer-term interactions with other extracellular matrix
      components. They share properties with other matrix molecules, cytokines, adaptor
      proteins, and chaperones, modulate the organization of collagen fibrils, and bind
      and localize an array of growth factors or proteases. At cell surfaces,
      interactions with an array of receptors activate cell-dependent signaling and
      phenotypic outcomes. Through these dynamic, pleiotropic, and context-dependent
      pathways, mammalian thrombospondins contribute to wound healing and angiogenesis,
      vessel wall biology, connective tissue organization, and synaptogenesis. We
      overview the domain organization and structure of thrombospondins, key features
      of their evolution, and their cell biology. We discuss their roles in vivo,
      associations with human disease, and ongoing translational applications. In many
      respects, we are only beginning to appreciate the important roles of these
      proteins in physiology and pathology.

PMID- 21875992
TI  - Mandibular incisor extraction: a systematic review of an uncommon extraction
      choice in orthodontic treatment.
AB  - OBJECTIVES: To review the published literature in order to address clinical
      questions regarding the indications, effects and outcomes of mandibular incisor
      extraction in orthodontics. DATA SOURCES: Three electronic databases were
      searched: PubMed (1950-January 2011), Ovid Embase+Ovid Embase Classic (1947
      January 2011) and Cochrane library (6 Cochrane databases, 1996-January 2011). The
      following journals were additionally searched: American Journal of Orthodontics
      and Dentofacial Orthopedics (1960-January 2011), Angle Orthodontist (1960-January
      2011), European Journal of Orthodontics (1970-January 2011) and Journal of
      Orthodontics (1974-January 2011). Grey literature was searched using Google
      Scholar and System for Information on Grey Literature in Europe. Secondary search
      of the references cited in the relevant articles was also conducted. DATA
      SELECTION: Articles in vivo, in Humans, in English, concerning treatment of
      malocclusion with mandibular incisor extractions or missing mandibular incisors.
      Fifty-four publications met these inclusion criteria and were reviewed. DATA
      EXTRACTION: Data were extracted independently by two reviewers with regard to:
      (1) indications; (2) contraindications; (3) effects; (4) outcomes; and (5)
      factors associated with successful outcomes. DATA SYNTHESIS: Considering the
      descriptive nature of the studies found, a narrative synthesis was undertaken.
      CONCLUSIONS: The descriptive nature of published articles precludes making strong
      evidence-based recommendations regarding this extraction choice, but it is clear
      that mandibular incisor extraction can be effectively used in the resolution of
      crowding, as well as intermaxillary malocclusion in carefully selected cases.
      Several factors that could lead to good outcomes of orthodontic treatment
      following mandibular incisor extraction were identified. Mild-to-moderate class
      III malocclusion, an edge-to-edge anterior occlusion or anterior crossbite, with
      mild anterior mandibular tooth size excess, and minimal open bite tendencies were
      the clinical situations most frequently treated with this unique extraction
      choice. On the other hand, clinicians should be careful to avoid poor outcomes
      such as gingival recession, open interproximal gingival embrasures, increased
      overjet and overbite.

PMID- 21875993
TI  - What are we reading now? An update on the papers published in the orthodontic
      literature (1999-2008).
AB  - AIMS: To assess differences between articles published in the Journal of
      Orthodontics (JO) and European Journal of Orthodontics (EJO) from 1999 to 2008
      and compare longitudinal publication profiles. DESIGN: Retrospective,
      observational. METHODS: The main study examined articles from the American
      Journal of Orthodontics and Dentofacial Orthopedics and Angle Orthodontist
      alongside the JO and EJO. All journals were hand-searched to identify eligible
      articles. A random sample from these articles was obtained to provide 80% power
      to detect a 100% increase in the number of randomized controlled trials (RCTs) at
      the 5% level of significance. Each article was classified according to pre
      determined criteria by one author (RG). Variations between journals were assessed
      using the chi-squared test or odds ratio (OR) and 95% confidence intervals (95%
      CI). RESULTS: A random sample of 425 articles was obtained from 4301 eligible
      articles, of which 113 were from the JO or EJO. About 34.5% of articles were from
      the JO and 66.5% the EJO. Statistically significant differences were found
      between the type (P<0.001), subject (P=0.049), method/direction (P=0.038) and
      controls (P=0.006) of articles published in the two journals. When compared
      longitudinally the proportion of RCTs published between 1989 and 1993 (2.8%) and
      1999-2008 (18.5%) was statistically significant (OR=8.0, 95% CI 2.8, 23.1).
      Statistically significant differences were seen over time in all aspects
      investigated. CONCLUSIONS: Statistically significant differences were found in
      the publication profiles of the two orthodontic journals during the period
      examined and longitudinally. A piece of clinical research was 8 times more likely
      to be an RCT during 1999-2008, compared to 1989-1993.

PMID- 21875994
TI  - The BOS MOrth Cases Prize 2009.
AB  - This paper describes the orthodontic treatment of two cases that were
      successfully entered for the 2009 MOrth Cases Prize. The first case describes the
      treatment of a class II division 1 malocclusion with increased vertical
      proportions that was treated with upper and lower self-ligating appliances and
      headgear for anchorage support. The second case describes the use of a Clark Twin
      Block appliance, with headgear, followed by non-extraction upper and lower fixed
      appliances to treat a class II division 1 malocclusion with an overjet of 14 mm.

PMID- 21875995
TI  - Do you do Damon(r)? What is the current evidence base underlying the philosophy
      of this appliance system?
AB  - Self-ligating bracket systems are increasing in popularity amongst orthodontists.
      This reflects their high quality engineering, improved reliability and relative
      ease of use. However, it might also be related to claims of superior function
      made by the manufacturers of these appliances. In particular, the Damon((r))
      appliance system claims to offer significant advantages to both orthodontist and
      patient over conventional-ligation and other forms of self-ligated appliances. We
      have reviewed current literature relating to use of the Damon((r)) appliance
      system. There is some evidence to suggest this appliance may lead to reductions
      in chairside time for the orthodontist, particularly those experienced with this
      system, in comparison to conventional-ligation. However, evidence that pain
      experience is reduced for the patient when using Damon((r)) brackets is not
      conclusive. In the presence of identical archwire sequences, there is no evidence
      that Damon((r)) brackets can align teeth faster or in a qualitatively differently
      manner, when compared with conventional-ligation. There is no high quality
      evidence that treatment with the Damon((r)) appliance takes place more rapidly or
      leads to a superior occlusal or aesthetic result. Indeed, the best available
      evidence would suggest there is no difference in treatment outcome or time, at
      least in extraction cases. There is no evidence that treatment with the
      Damon((r)) appliance is more stable. Claims relating to improved clinical
      performance of the Damon((r)) appliance system are currently being made to
      orthodontists and patients that are not substantiated in the scientific
      literature.

PMID- 21875998
TI  - Letters to the editor.

PMID- 21875999
TI  - The COMPASS family of H3K4 methylases in Drosophila.
AB  - Methylation of histone H3 lysine 4 (H3K4) in Saccharomyces cerevisiae is
      implemented by Set1/COMPASS, which was originally purified based on the
      similarity of yeast Set1 to human MLL1 and Drosophila melanogaster Trithorax
      (Trx). While humans have six COMPASS family members, Drosophila possesses a
      representative of the three subclasses within COMPASS-like complexes: dSet1
      (human SET1A/SET1B), Trx (human MLL1/2), and Trr (human MLL3/4). Here, we report
      the biochemical purification and molecular characterization of the Drosophila
      COMPASS family. We observed a one-to-one similarity in subunit composition with
      their mammalian counterparts, with the exception of LPT (lost plant homeodomains
      [PHDs] of Trr), which copurifies with the Trr complex. LPT is a previously
      uncharacterized protein that is homologous to the multiple PHD fingers found in
      the N-terminal regions of mammalian MLL3/4 but not Drosophila Trr, indicating
      that Trr and LPT constitute a split gene of an MLL3/4 ancestor. Our study
      demonstrates that all three complexes in Drosophila are H3K4 methyltransferases;
      however, dSet1/COMPASS is the major monoubiquitination-dependent H3K4 di- and
      trimethylase in Drosophila. Taken together, this study provides a springboard for
      the functional dissection of the COMPASS family members and their role in the
      regulation of histone H3K4 methylation throughout development in Drosophila.

PMID- 21876000
TI  - Biphasic and dosage-dependent regulation of osteoclastogenesis by beta-catenin.
AB  - Wnt/beta-catenin signaling is a critical regulator of skeletal physiology.
      However, previous studies have mainly focused on its roles in osteoblasts, while
      its specific function in osteoclasts is unknown. This is a clinically important
      question because neutralizing antibodies against Wnt antagonists are promising
      new drugs for bone diseases. Here, we show that in osteoclastogenesis, beta
      catenin is induced during the macrophage colony-stimulating factor (M-CSF)
      mediated quiescence-to-proliferation switch but suppressed during the RANKL
      mediated proliferation-to-differentiation switch. Genetically, beta-catenin
      deletion blocks osteoclast precursor proliferation, while beta-catenin
      constitutive activation sustains proliferation but prevents osteoclast
      differentiation, both causing osteopetrosis. In contrast, beta-catenin
      heterozygosity enhances osteoclast differentiation, causing osteoporosis.
      Biochemically, Wnt activation attenuates whereas Wnt inhibition stimulates
      osteoclastogenesis. Mechanistically, beta-catenin activation increases GATA2/Evi1
      expression but abolishes RANKL-induced c-Jun phosphorylation. Therefore, beta
      catenin exerts a pivotal biphasic and dosage-dependent regulation of
      osteoclastogenesis. Importantly, these findings suggest that Wnt activation is a
      more effective treatment for skeletal fragility than previously recognized that
      confers dual anabolic and anti-catabolic benefits.

PMID- 21876001
TI  - Ras-induced and extracellular signal-regulated kinase 1 and 2 phosphorylation
      dependent isomerization of protein tyrosine phosphatase (PTP)-PEST by PIN1
      promotes FAK dephosphorylation by PTP-PEST.
AB  - Protein tyrosine phosphatase (PTP)-PEST is a critical regulator of cell adhesion
      and migration. However, the mechanism by which PTP-PEST is regulated in response
      to oncogenic signaling to dephosphorylate its substrates remains unclear. Here,
      we demonstrate that activated Ras induces extracellular signal-regulated kinase 1
      and 2-dependent phosphorylation of PTP-PEST at S571, which recruits PIN1 to bind
      to PTP-PEST. Isomerization of the phosphorylated PTP-PEST by PIN1 increases the
      interaction between PTP-PEST and FAK, which leads to the dephosphorylation of FAK
      Y397 and the promotion of migration, invasion, and metastasis of v-H-Ras
      transformed cells. These findings uncover an important mechanism for the
      regulation of PTP-PEST in activated Ras-induced tumor progression.

PMID- 21876002
TI  - Calpain-1 cleaves Rad21 to promote sister chromatid separation.
AB  - Defining the mechanisms of chromosomal cohesion and dissolution of the cohesin
      complex from chromatids is important for understanding the chromosomal
      missegregation seen in many tumor cells. Here we report the identification of a
      novel cohesin-resolving protease and describe its role in chromosomal
      segregation. Sister chromatids are held together by cohesin, a multiprotein ring
      like complex comprised of Rad21, Smc1, Smc3, and SA2 (or SA1). Cohesin is known
      to be removed from vertebrate chromosomes by two distinct mechanisms, namely, the
      prophase and anaphase pathways. First, PLK1-mediated phosphorylation of SA2 in
      prophase leads to release of cohesin from chromosome arms, leaving behind
      centromeric cohesins that continue to hold the sisters together. Then, at the
      onset of anaphase, activated separase cleaves the centromeric cohesin Rad21,
      thereby opening the cohesin ring and allowing the sister chromatids to separate.
      We report here that the calcium-dependent cysteine endopeptidase calpain-1 is a
      Rad21 peptidase and normally localizes to the interphase nuclei and chromatin.
      Calpain-1 cleaves Rad21 at L192, in a calcium-dependent manner. We further show
      that Rad21 cleavage by calpain-1 promotes separation of chromosome arms, which
      coincides with a calcium-induced partial loss of cohesin at several chromosomal
      loci. Engineered cleavage of Rad21 at the calpain-cleavable site without
      activation of calpain-1 can lead to a loss of sister chromatid cohesion.
      Collectively, our work reveals a novel function of calpain-1 and describes an
      additional pathway for sister chromatid separation in humans.

PMID- 21876004
TI  - Severe tinnitus and depressive symptoms: a complex interaction.

PMID- 21876005
TI  - A critical review of the interior shape of the ear canal.

PMID- 21876009
TI  - Bid to expand horizon of medical students fails.

PMID- 21876003
TI  - Functional interplay of the Mre11 nuclease and Ku in the response to replication
      associated DNA damage.
AB  - The Mre11 complex is a central component of the DNA damage response, with roles
      in damage sensing, molecular bridging, and end resection. We have previously
      shown that in Saccharomyces cerevisiae, Ku70 (yKu70) deficiency reduces the
      ionizing radiation sensitivity of mre11Delta mutants. In this study, we show that
      yKu70 deficiency suppressed the camptothecin (CPT) and methyl methanesulfonate
      (MMS) sensitivity of nuclease-deficient mre11-3 and sae2Delta mutants in an Exo1
      dependent manner. CPT-induced G(2)/M arrest, gamma-H2AX persistence, and
      chromosome breaks were elevated in mre11-3 mutants. These outcomes were reduced
      by yKu70 deficiency. Given that the genotoxic effects of CPT are manifest during
      DNA replication, these data suggest that Ku limits Exo1-dependent double-strand
      break (DSB) resection during DNA replication, inhibiting the initial processing
      steps required for homology-directed repair. We propose that Mre11 nuclease- and
      Sae2-dependent DNA end processing, which initiates DSB resection prevents Ku from
      engaging DSBs, thus promoting Exo1-dependent resection. In agreement with this
      idea, we show that Ku affinity for binding to short single-stranded overhangs is
      much lower than for blunt DNA ends. Collectively, the data define a nonhomologous
      end joining (NHEJ)-independent, S-phase-specific function of the Ku heterodimer.

PMID- 21876010
TI  - Pack pooches in the cargo hold, CMA says.

PMID- 21876011
TI  - On freedom.

PMID- 21876012
TI  - Company profits from side effects of glaucoma treatment.

PMID- 21876013
TI  - CMA president-elect traverses wildernesses.

PMID- 21876014
TI  - Mortality associated with withdrawal of life-sustaining therapy for patients with
      severe traumatic brain injury: a Canadian multicentre cohort study.
AB  - BACKGROUND: Severe traumatic brain injury often leads to death from withdrawal of
      life-sustaining therapy, although prognosis is difficult to determine. METHODS:
      To evaluate variation in mortality following the withdrawal of life-sustaining
      therapy and hospital mortality in patients with critical illness and severe
      traumatic brain injury, we conducted a two-year multicentre retrospective cohort
      study in six Canadian level-one trauma centres. The effect of centre on hospital
      mortality and withdrawal of life-sustaining therapy was evaluated using
      multivariable logistic regression adjusted for baseline patient-level covariates
      (sex, age, pupillary reactivity and score on the Glasgow coma scale). RESULTS: We
      randomly selected 720 patients with traumatic brain injury for our study. The
      overall hospital mortality among these patients was 228/720 (31.7%, 95%
      confidence interval [CI] 28.4%-35.2%) and ranged from 10.8% to 44.2% across
      centres (chi(2) test for overall difference, p < 0.001). Most deaths (70.2%
      [160/228], 95% CI 63.9%-75.7%) were associated with withdrawal of life-sustaining
      therapy, ranging from 45.0% (18/40) to 86.8% (46/53) (chi(2) test for overall
      difference, p < 0.001) across centres. Adjusted odd ratios (ORs) for the effect
      of centre on hospital mortality ranged from 0.61 to 1.55 (p < 0.001). The
      incidence of withdrawal of life-sustaining therapy varied by centre, with ORs
      ranging from 0.42 to 2.40 (p = 0.001). About one half of deaths that occurred
      following the withdrawal of life-sustaining therapies happened within the first
      three days of care. INTERPRETATION: We observed significant variation in
      mortality across centres. This may be explained in part by regional variations in
      physician, family or community approaches to the withdrawal of life-sustaining
      therapy. Considering the high proportion of early deaths associated with the
      withdrawal of life-sustaining therapy and the limited accuracy of current
      prognostic indicators, caution should be used regarding early withdrawal of life
      sustaining therapy following severe traumatic brain injury.

PMID- 21876015
TI  - A defence of the vermiform appendix.

PMID- 21876016
TI  - Withdrawing life-sustaining therapy for patients with severe traumatic brain
      injury.

PMID- 21876018
TI  - Mediocrity has become the norm, Turnbull asserts in valedictory address.

PMID- 21876017
TI  - Thoracic balls.

PMID- 21876019
TI  - Mobilize at government doorsteps, CMA president urges.

PMID- 21876020
TI  - Support urged for physicians who speak out on health care issues.

PMID- 21876021
TI  - Panel's recommendations could open privatization floodgates, delegates warn.

PMID- 21876022
TI  - CMA urges prescription-only antibiotics for agricultural use.

PMID- 21876023
TI  - Federal government unveils patient-oriented research strategy.

PMID- 21876024
TI  - Brevity is the soul of advocacy, experts say.

PMID- 21876025
TI  - No user fees, but perhaps user fees.

PMID- 21876026
TI  - Ontario physicians get liability fee break.

PMID- 21876027
TI  - Use of angiotensin-converting-enzyme inhibitors or angiotensin-receptor blockers
      and cancer risk: a meta-analysis of observational studies.
AB  - BACKGROUND: Epidemiologic studies have reported inconsistent findings regarding
      the association between the use of angiotensin-converting-enzyme (ACE) inhibitors
      or angiotensin-receptor blockers and the risk of cancer. We performed a meta
      analysis of observational studies to assess the association. METHODS: We searched
      MEDLINE, EMBASE and the Cochrane Library to identify studies through January
      2011. Two evaluators independently reviewed and selected articles of cohort and
      case-control studies on the basis of predetermined selection criteria. RESULTS:
      Of 3970 screened articles, 12 cohort studies and 16 case-control studies were
      selected for analysis. We found no significant association between the use of ACE
      inhibitors or angiotensin-receptor blockers and the overall risk of cancer
      (relative risk [RR] 0.96, 95% confidence interval [CI] 0.90-1.03). We found a
      decreased risk of cancer associated with use of either medication when we
      restricted the analyses to cohort and nested case-control studies (RR 0.90, 95%
      CI 0.83-0.97) or to studies with long-term follow-up of more than five years (RR
      0.89, 95% CI 0.83-0.96). In the subgroup meta-analyses by cancer site, a
      decreased risk was identified for esophageal cancer, whereas an increased risk
      was found for melanoma and kidney cancer. INTERPRETATION: No significant
      association was found between the use of ACE inhibitors or angiotensin-receptor
      blockers and overall risk of cancer. A possible beneficial effect associated with
      use of either medication was suggested in sensitivity analyses, including those
      of studies with long-term follow-up. Large randomized controlled trials with long
      term follow-up are needed to specifically test the effect of each of these
      medications on the risk of cancer.

PMID- 21876028
TI  - Unlocking Health Canada's cache of trade secrets: mandatory disclosure of
      clinical trial results.

PMID- 21876029
TI  - Specialty training out-of-sync with job market.

PMID- 21876030
TI  - The lucky penny: an illustration of the bullet rule.

PMID- 21876031
TI  - Glenohumeral muscle activation during provocative tests designed to diagnose
      superior labrum anterior-posterior lesions.
AB  - BACKGROUND: Despite considerable medical advances, arthroscopy remains the only
      definitive means of superior labrum anterior-posterior (SLAP) lesion diagnosis.
      Natural shoulder anatomic variants limit the reliability of radiographic findings
      and clinical evaluations are not consistent. Accurate clinical diagnostic
      techniques would be advantageous because of the invasiveness, patient risk, and
      financial cost associated with arthroscopy. PURPOSE: The purpose of this study
      was to examine the behavior of the joint-stabilizing muscles in provocative tests
      for SLAP lesions. Electromyography was used to characterize the muscle behavior,
      with particular interest in the long head of the biceps brachii (LHBB), as
      activation of the long head and subsequent tension in the biceps tendon should,
      based on related research, elicit labral symptoms in SLAP lesion patients. STUDY
      DESIGN: Controlled laboratory study. METHODS: Volunteers (N = 21) without a
      history of shoulder injury were recruited. The tests analyzed were active
      compression, Speed's, pronated load, biceps load I, biceps load II, resisted
      supination external rotation, and Yergason's. Tests were performed with a
      dynamometer to improve reproducibility. Muscle activity was recorded for the long
      and short heads of the biceps brachii, anterior deltoid, pectoralis major,
      latissimus dorsi, infraspinatus, and supraspinatus. Muscle behavior for each test
      was characterized by peak activation and proportion of muscle activity. RESULTS:
      Speed's, active compression palm-up, bicep I, and bicep II produced higher long
      head activations. Resisted supination external rotation, bicep I, bicep II, and
      Yergason's produced a higher LHBB proportion. CONCLUSION: Biceps load I and
      biceps load II elicited promising long head behavior (high activation and
      selectivity). Speed's and active compression palm up elicited higher activation
      of the LHBB, and resisted supination and Yergason's elicited selective LHBB
      activity. These top performing tests utilize a unique range of test variables
      that may prove valuable for optimal SLAP test design and performance. CLINICAL
      RELEVANCE: This study examines several provocative tests that are frequently used
      in the clinical setting as a means of evaluating a potential SLAP lesion.

PMID- 21876032
TI  - Cigarette smoking and inflammation: cellular and molecular mechanisms.
AB  - Cigarette smoke (CS) causes considerable morbidity and mortality by inducing
      cancer, chronic lung and vascular diseases, and oral disease. Despite the well
      recognized risks associated with smoking, the habit remains unacceptably
      prevalent. Several toxins present in CS have immunomodulatory effects. CS also
      contains trace amounts of microbial cell components, including bacterial
      lipopolysaccharide. These and other CS constituents induce chronic inflammation
      at mucosal surfaces and modify host responses to exogenous antigens. The effects
      of CS on immunity are far-reaching and complex; both pro-inflammatory and
      suppressive effects may be induced. The net effect of CS on immunity depends on
      many variables, including the dose and type of tobacco, the route and chronicity
      of exposure, and the presence of other factors at the time of immune cell
      stimulation, such as Toll receptor ligands or other inflammatory mediators. CS
      impairs innate defenses against pathogens, modulates antigen presentation, and
      promotes autoimmunity. CS also impairs immunity in the oral cavity and promotes
      gingival and periodontal disease and oral cancer. The recognition of specific
      mechanisms by which CS affects host immunity is an important step toward
      elucidating mechanisms of tobacco-induced disease and may identify novel
      therapeutic approaches for the management of diseases that afflict smokers.

PMID- 21876033
TI  - Cancer immunoediting of the NK group 2D ligand H60a.
AB  - Cancer immunoediting describes the process whereby highly immunogenic tumor cells
      are removed, or edited, from the primary tumor repertoire by the immune system.
      In immunodeficient mice, the editing process is hampered, and "unedited" tumor
      cells can be recovered and studied. In this study, we compared unedited and
      edited tumors for their expression of NK group 2D (NKG2D) ligands, a family of
      surface proteins expressed on tumor cells that can activate NK cell cytotoxic
      activity. We found that the expression of the NKG2D ligand H60a was more
      heterogeneous in groups of unedited 3'-methylcholanthrene sarcoma cell lines
      compared with that in edited 3'-methylcholanthrene sarcoma cell lines (i.e., some
      unedited cell lines expressed very high levels of H60a, whereas other unedited
      and edited cell lines expressed very low levels). We also found that some highly
      immunogenic cell lines displayed a bimodal distribution consisting of H60a-hi and
      H60a-lo cells. In one of these cell lines, the H60a-hi cells could be removed by
      passaging the cells through RAG2(-/-) mice, resulting in edited cell lines that
      were poor targets for NK cells and that displayed progressive tumor growth. This
      editing of H60a-hi cells required NK cells and NKG2D. Our studies show that the
      expression of H60a on tumors cells can be actively modulated by the immune
      system, thereby implicating this NKG2D ligand in tumor immunosurveillance.

PMID- 21876035
TI  - Transgenic Eimeria tenella expressing enhanced yellow fluorescent protein
      targeted to different cellular compartments stimulated dichotomic immune
      responses in chickens.
AB  - Eimeria tenella, one of the seven species of chicken coccidia, elicits protective
      immunity against challenge infection with both homologous and heterologous
      strains. We endeavor to use recombinant E. tenella as a vaccine vehicle for
      expressing and delivering pathogen Ags and investigate immune responses against
      these foreign Ags. In this study, two lines of transgenic E. tenella expressing a
      model Ag, enhanced yellow fluorescent protein (EYFP), targeted to the micronemes
      and to the cytoplasm of the recombinant parasites were constructed to study the
      impact of Ag compartmentalization on immunogenicity. The MTT assay, intracellular
      cytokine staining, and real-time PCR were performed to detect the EYFP-specific
      proliferation and effector functions of splenic lymphocytes of immunized
      chickens. ELISA was used to measure anti-EYFP IgG and IgA responses. The results
      showed that both lines of transgenic parasites stimulated EYFP-specific
      lymphocyte proliferation and IFN-gamma expression in CD4 and CD8 T cells, whereas
      a higher level of Ag-specific lymphocyte proliferation was elicited by the
      transgenic line expressing microneme-targeted EYFP. Furthermore, this line
      stimulated stronger IgA response than the one expressing cytoplasm-targeted EYFP
      after the second immunization. Our findings are encouraging for further
      investigation of the effect of Ag compartmentalization in transgenic Eimeria on
      immunogenicity and for the development of a eukaryotic vaccine vector using
      genetically modified Apicomplexa parasites.

PMID- 21876034
TI  - IL-2 regulates expression of C-MAF in human CD4 T cells.
AB  - Blockade of IL-2R with humanized anti-CD25 Abs, such as daclizumab, inhibits Th2
      responses in human T cells. Recent murine studies have shown that IL-2 also plays
      a significant role in regulating Th2 cell differentiation by activated STAT5. To
      explore the role of activated STAT5 in the Th2 differentiation of primary human T
      cells, we studied the mechanisms underlying IL-2 regulation of C-MAF expression.
      Chromatin immunoprecipitation studies revealed that IL-2 induced STAT5 binding to
      specific sites in the C-MAF promoter. These sites corresponded to regions
      enriched for markers of chromatin architectural features in both resting CD4 and
      differentiated Th2 cells. Unlike IL-6, IL-2 induced C-MAF expression in CD4 T
      cells with or without prior TCR stimulation. TCR-induced C-MAF expression was
      significantly inhibited by treatment with daclizumab or a JAK3 inhibitor, R333.
      Furthermore, IL-2 and IL-6 synergistically induced C-MAF expression in TCR
      activated T cells, suggesting functional cooperation between these cytokines.
      Finally, both TCR-induced early IL4 mRNA expression and IL-4 cytokine expression
      in differentiated Th2 cells were significantly inhibited by IL-2R blockade. Thus,
      our findings demonstrate the importance of IL-2 in Th2 differentiation in human T
      cells and support the notion that IL-2R-directed therapies may have utility in
      the treatment of allergic disorders.

PMID- 21876036
TI  - Combining liver- and blood-stage malaria viral-vectored vaccines: investigating
      mechanisms of CD8+ T cell interference.
AB  - Replication-deficient adenovirus and modified vaccinia virus Ankara (MVA) vectors
      expressing single pre-erythrocytic or blood-stage Plasmodium falciparum Ags have
      entered clinical testing using a heterologous prime-boost immunization approach.
      In this study, we investigated the utility of the same immunization regimen when
      combining viral vectored vaccines expressing the 42-kDa C terminus of the blood
      stage Ag merozoite surface protein 1 and the pre-erythrocytic Ag circumsporozoite
      protein in the Plasmodium yoelii mouse model. We find that vaccine
      coadministration leads to maintained Ab responses and efficacy against blood
      stage infection, but reduced secondary CD8(+) T cell responses against both Ags
      and efficacy against liver-stage infection. CD8(+) T cell interference can be
      minimized by coadministering the MVA vaccines at separate sites, resulting in
      enhanced liver-stage efficacy in mice immunized against both Ags compared with
      just one. CD8(+) T cell interference (following MVA coadministration as a
      mixture) may be caused partly by a lack of physiologic space for high-magnitude
      responses against multiple Ags, but is not caused by competition for presentation
      of Ag on MHC class I molecules, nor is it due to restricted T cell access to APCs
      presenting both Ags. Instead, enhanced killing of peptide-pulsed cells is
      observed in mice possessing pre-existing T cells against two Ags compared with
      just one, suggesting that priming against multiple Ags may in part reduce the
      potency of multiantigen MVA vectors to stimulate secondary CD8(+) T cell
      responses. These data have important implications for the development of a
      multistage or multicomponent viral vectored malaria vaccine for use in humans.

PMID- 21876037
TI  - TCR-induced activation of LFA-1 involves signaling through Tiam1.
AB  - Adhesion is pivotal for most leukocyte functions, and the beta(2) integrin family
      of adhesion molecules plays a central role. The integrins need activation to
      become functional, but the molecular events resulting in adhesion have remained
      incompletely understood. In human T cells, activation through the TCR results in
      specific phosphorylation of the T758 on the beta(2) chain of LFA-1. We now show
      that this phosphorylation leads to downstream binding of 14-3-3 proteins,
      followed by engagement of the guanine nucleotide exchange factor protein Tiam1
      and Rac1 activation. Downregulation of the signaling molecules inhibits LFA-1
      activity. Activation by the chemokine stromal cell-derived factor-1alpha also
      results in T758 phosphorylation and integrin activation. Thus, TCR and chemokine
      activation converges on LFA-1 phosphorylation, followed by similar downstream
      events affecting adhesion.

PMID- 21876038
TI  - TLR regulation of SPSB1 controls inducible nitric oxide synthase induction.
AB  - The mammalian innate immune system has evolved to recognize foreign molecules
      derived from pathogens via the TLRs. TLR3 and TLR4 can signal via the TIR domain
      containing adapter inducing IFN-beta (TRIF), which results in the transcription
      of a small array of genes, including IFN-beta. Inducible NO synthase (iNOS),
      which catalyzes the production of NO, is induced by a range of stimuli, including
      cytokines and microbes. NO is a potent source of reactive nitrogen species that
      play an important role in killing intracellular pathogens and forms a crucial
      component of host defense. We have recently identified iNOS as a target of the
      mammalian SPSB2 protein. The SOCS box is a peptide motif, which, in conjunction
      with elongins B and C, recruits cullin-5 and Rbx-2 to form an active E3 ubiquitin
      ligase complex. In this study, we show that SPSB1 is the only SPSB family member
      to be regulated by the same TLR pathways that induce iNOS expression and
      characterize the interaction between SPSB1 and iNOS. Through the use of SPSB1
      transgenic mouse macrophages and short hairpin RNA knockdown of SPSB1, we show
      that SPSB1 controls both the induction of iNOS and the subsequent production of
      NO downstream of TLR3 and TLR4. Further, we demonstrate that regulation of iNOS
      by SPSB1 is dependent on the proteasome. These results suggest that SPSB1 acts
      through a negative-feedback loop that, together with SPSB2, controls the extent
      of iNOS induction and NO production.

PMID- 21876040
TI  - Population trends and late-life disability in Hispanics from the Midwest.
AB  - OBJECTIVES: To describe the growth of the Hispanic population in the Midwest
      states of the United States, to present disability levels in older Mexican and
      non-Mexican-origin Midwest Hispanics by place of birth and poverty status, and
      compare disability levels among older Midwest Hispanics with those among
      Southwest Hispanics as well as non-Hispanics Whites and African Americans in each
      region. METHOD: Population data come from decennial U.S. Census Bureau surveys.
      Disability data for adults >= 50 years old come from the 2008 American Community
      Survey. RESULTS: The Hispanic population in the Midwest has tripled since 1980
      and now constitutes 6.6% of the entire Midwest population. Older Midwest
      Hispanics are somewhat younger, have a higher male-female ratio, and are more
      likely to be born outside the continental United States than Southwest Hispanics.
      In the Midwest, foreign-born Mexican American men report the lowest disability
      levels. Foreign-born Hispanic women of non-Mexican origin report the highest
      disability levels. Overall, older Hispanics have intermediate disability levels
      relative to non-Hispanic Whites and African Americans. Midwest Hispanics report
      less disability than Southwest Hispanics. DISCUSSION: There is substantial
      heterogeneity in late-life disability among Midwest Hispanics, which may be
      related to place of birth and of origin. Future research is needed to examine age
      at immigration and health selection as potential reasons for low disability
      levels among foreign-born Mexican American men.

PMID- 21876039
TI  - Human natural regulatory T cell development, suppressive function, and postthymic
      maturation in a humanized mouse model.
AB  - CD4(+) regulatory T cells (Tregs) control adaptive immune responses and promote
      self-tolerance. Various humanized mouse models have been developed in efforts to
      reproduce and study a human immune system. However, in models that require T cell
      differentiation in the recipient murine thymus, only low numbers of T cells
      populate the peripheral immune systems. T cells are positively selected by mouse
      MHC and therefore do not function well in an HLA-restricted manner. In contrast,
      cotransplantation of human fetal thymus/liver and i.v. injection of CD34(+) cells
      from the same donor achieves multilineage human lymphohematopoietic
      reconstitution, including dendritic cells and formation of secondary lymphoid
      organs, in NOD/SCID mice. Strong Ag-specific immune responses and homeostatic
      expansion of human T cells that are dependent on peripheral human APCs occur. We
      now demonstrate that FOXP3(+)Helios(+) "natural" Tregs develop normally in human
      fetal thymic grafts and are present in peripheral blood, spleen, and lymph nodes
      of these humanized mice. Humanized mice exhibit normal reversal of CD45 isoform
      expression in association with thymic egress, postthymic "naive" to "activated"
      phenotypic conversion, and suppressive function. These studies demonstrate the
      utility of this humanized mouse model for the study of human Treg ontogeny,
      immunobiology and therapy.

PMID- 21876041
TI  - Role of lipid II and membrane thickness in the mechanism of action of the
      lantibiotic bovicin HC5.
AB  - Lantibiotics are antimicrobial peptides produced by Gram-positive bacteria, nisin
      being the most well-known member. Nisin inhibits peptidoglycan synthesis and
      forms pores at sensitive membranes upon interaction with lipid II, the essential
      bacterial cell wall precursor. Bovicin HC5, a bacteriocin produced by
      Streptococcus bovis HC5, has the putative N-terminal lipid II binding motif, and
      we investigated the mode of action of bovicin HC5 using both living bacteria and
      model membranes, with special emphasis on the role of lipid II. Bovicin HC5
      showed activity against Staphylococcus cohnii and Staphylococcus warneri, but
      bovicin HC5 hardly interfered with the membrane potential of S. cohnii. In model
      membranes, bovicin HC5 was not able to cause carboxyfluorescein release or proton
      influx from DOPC vesicles containing lipid II. Bovicin HC5 blocked lipid II
      dependent pore formation activity of nisin, and a high-affinity interaction with
      lipid II was observed (apparent binding constant [K(a)] = 3.1 * 10(6) M(-1)),
      with a 1:1 stoichiometry. In DOPC vesicles containing lipid II, bovicin HC5 was
      able to assemble with lipid II into a prepore-like structure. Furthermore, we
      observed pore formation activity of bovicin HC5, which was stimulated by the
      presence of lipid II, in thin membranes. Moreover, bovicin HC5 induced the
      segregation of lipid II into domains in giant model membrane vesicles. In
      conclusion, bovicin HC5 has a primary mode of action similar to that of nisin,
      but some differences regarding the pore-forming capacity were demonstrated.

PMID- 21876043
TI  - Pharmacokinetics of voriconazole administered concomitantly with fluconazole and
      population-based simulation for sequential use.
AB  - In clinical practice, antifungal therapy may be switched from fluconazole to
      voriconazole; such sequential use poses the potential for drug interaction due to
      cytochrome P450 2C19 (CYP2C19)-mediated inhibition of voriconazole metabolism.
      This open-label, randomized, two-way crossover study investigated the effect of
      concomitant fluconazole on voriconazole pharmacokinetics in 10 subjects: 8
      extensive metabolizers and 2 poor metabolizers of CYP2C19. The study consisted of
      4-day voriconazole-only and 5-day voriconazole-plus-fluconazole treatments,
      separated by a 14-day washout. Voriconazole pharmacokinetics were determined by
      noncompartmental analyses. A physiologically based pharmacokinetic model was
      developed in Simcyp (Simcyp Ltd., Sheffield, United Kingdom) to predict the
      magnitude of drug interaction should antifungal therapy be switched from
      fluconazole to voriconazole, following various simulated lag times for the
      switch. In CYP2C19 extensive metabolizers, fluconazole increased the maximum
      plasma concentration and the area under the plasma concentration-time curve (AUC)
      of voriconazole by 57% and 178%, respectively. In poor metabolizers, however,
      voriconazole pharmacokinetics were unaffected by fluconazole. The simulations
      based on pharmacokinetic modeling predicted that if voriconazole was started 6,
      12, 24, or 36 h after the last dose of fluconazole, the voriconazole AUC ratios
      (sequential therapy versus voriconazole only) after the first dose would be 1.51,
      1.41, 1.28, and 1.14, respectively. This suggests that the remaining systemic
      fluconazole would result in a marked drug interaction with voriconazole for >= 24
      h. Although no safety issues were observed during coadministration, concomitant
      use of fluconazole and voriconazole is not recommended. Frequent monitoring for
      voriconazole-related adverse events is advisable if voriconazole is used
      sequentially after fluconazole.

PMID- 21876042
TI  - Ctriporin, a new anti-methicillin-resistant Staphylococcus aureus peptide from
      the venom of the scorpion Chaerilus tricostatus.
AB  - Antibiotic-resistant microbes, such as methicillin-resistant Staphylococcus
      aureus, seriously threaten human health. The outbreak of "superbugs" in recent
      years emphasizes once again the need for the development of new antimicrobial
      agents or resources. Antimicrobial peptides have an evident bactericidal effect
      against multidrug-resistant pathogens. In the present study, a new antimicrobial
      peptide, ctriporin, was cloned and characterized from the venom of the scorpion
      Chaerilus tricostatus, an animal which has not yet been explored for toxic
      peptide resources. The MICs of ctriporin against Staphylococcus aureus, Bacillus
      thuringiensis, Bacillus subtilis, Micrococcus luteus, and Candida albicans are 5
      to 20 MUg/ml. Meanwhile, it MIC against clinical antibiotic-resistant bacterial
      strains is 10 MUg/ml. Furthermore, the potential for ctriporin to be used as a
      topical antibiotic for treating staphylococcal skin infections was investigated.
      External use of the peptide ctriporin dramatically decreased the bacterial counts
      and cured skin infections in mice. In addition, ctriporin demonstrates
      antimicrobial efficacy via the bactericidal mechanism of rapid cell lysis.
      Together, these results suggest the potential of developing ctriporin as a new
      topical antibiotic.

PMID- 21876044
TI  - Application of bacterial bioluminescence to assess the efficacy of fast-acting
      biocides.
AB  - Traditional microbiological techniques are used to provide reliable data on the
      rate and extent of kill for a range of biocides. However, such techniques provide
      very limited data regarding the initial rate of kill of fast-acting biocides over
      very short time domains. This study describes the application of a recombinant
      strain of Escherichia coli expressing the Photorhabdus luminescens lux operon as
      a whole-cell biosensor. Light emission is linked directly to bacterial
      metabolism; therefore, by monitoring light output, the impact of fast-acting
      biocides can be assessed. Electrochemically activated solutions (ECASs), bleach,
      Virkon, and ethanol were assessed at three concentrations (1%, 10%, 80%) in the
      presence of organic soiling. Over a 2-s time course, 80% ECAS produced the
      greatest reduction in light output in the absence of organic load but was
      strongly inhibited by its presence. Eighty percent ethanol outperformed all
      tested biocides in the presence of organic soil. Bleach and Virkon produced
      similar reductions in bioluminescence at matched concentrations within the time
      course of the assay. It was also demonstrated that the assay can be used to
      rapidly assess the impact of organic soiling. The use of bioluminescent bacteria
      as whole-cell bioreporters allows assessment of the relative efficacies of fast
      acting biocides within milliseconds of application. The assay can be used to
      investigate activity over short or extended time domains to confirm complete
      metabolic inhibition of the bioreporter. Moreover, the assay may enable further
      elucidation of their mechanism of action by allowing the investigation of
      activity over time domains precluded by traditional microbiology.

PMID- 21876046
TI  - Mortality in hematologic malignancy and hematopoietic stem cell transplant
      patients with mucormycosis, 2001 to 2009.
AB  - Mortality due to mucormycosis is high. We assessed clinical characteristics and
      mortality among stem cell transplant and hematologic malignancy patients
      diagnosed with mucormycosis from 2001 to 2009. Thirty patients were diagnosed
      with probable or proven mucormycosis during the study. Twenty-six were diagnosed
      premortem, and most were treated with liposomal amphotericin B single-agent
      antifungal therapy initially. While the initial antifungal and surgical treatment
      approach remained stable throughout the study period, 6-week mortality
      significantly declined over time (67% in 2001 to 2003 versus 45% in 2004 to 2006
      versus 20% in 2007 to 2009 [P = 0.04]), as did 12-week mortality (78% in 2001 to
      2003 versus 55% in 2004 to 2006 versus 20% in 2007 to 2009 [P = 0.01]).

PMID- 21876045
TI  - Efficient identification of human immunodeficiency virus type 1 mutants resistant
      to a protease inhibitor by using a random mutant library.
AB  - Emergence of drug-resistant mutant viruses during the course of antiretroviral
      therapy is a major hurdle that limits the success of chemotherapeutic treatment
      to suppress human immunodeficiency virus type 1 (HIV-1) replication and AIDS
      progression. Development of new drugs and careful patient management based on
      resistance genotyping data are important for enhancing therapeutic efficacy.
      However, identifying changes leading to drug resistance can take years of
      clinical studies, and conventional in vitro assays are limited in generating
      reliable drug resistance data. Here we present an efficient in vitro screening
      assay for selecting drug-resistant variants from a library of randomly mutated
      HIV-1 strains generated by transposon-directed base-exchange mutagenesis. As a
      test of principle, we screened a library of mutant HIV-1 strains containing
      random mutations in the protease gene by using a reporter T-cell line in the
      presence of the protease inhibitor (PI) nelfinavir (NFV). Analysis of replicating
      viruses from a single round of infection identified 50 amino acid substitutions
      at 35 HIV-1 protease residue positions. The selected mutant viruses showed
      specific resistance to NFV and included most of the known NFV resistance
      mutations. Therefore, the new assay is efficient for identifying changes leading
      to drug resistance. The data also provide insights into the molecular mechanisms
      underlying the development of drug resistance.

PMID- 21876047
TI  - Wild-type MIC distributions and epidemiological cutoff values for amphotericin B
      and Aspergillus spp. for the CLSI broth microdilution method (M38-A2 document).
AB  - Although clinical breakpoints have not been established for mold testing,
      epidemiological cutoff values (ECVs) are available for Aspergillus spp. versus
      the triazoles and caspofungin. Wild-type (WT) MIC distributions (organisms in a
      species-drug combination with no acquired resistance mechanisms) were defined in
      order to establish ECVs for six Aspergillus spp. and amphotericin B. Two sets
      (CLSI/EUCAST broth microdilution) of available MICs were evaluated: those for A.
      fumigatus (3,988/833), A. flavus (793/194), A. nidulans (184/69), A. niger
      (673/140), A. terreus (545/266), and A. versicolor (135/22). Three sets of data
      were analyzed: (i) CLSI data gathered in eight independent laboratories in
      Canada, Europe, and the United States; (ii) EUCAST data from a single laboratory;
      and (iii) the combined CLSI and EUCAST data. ECVs, expressed in MUg/ml, that
      captured 95%, 97.5%, and 99% of the modeled wild-type population (CLSI and
      combined data) were as follows: for A. fumigatus, 2, 2, and 4; for A. flavus, 2,
      4, and 4; for A. nidulans, 4, 4, and 4; for A. niger, 2, 2, and 2; for A.
      terreus, 4, 4, and 8; and for A. versicolor, 2, 2, and 2. Similar to the case for
      the triazoles and caspofungin, amphotericin B ECVs may aid in the detection of
      strains with acquired mechanisms of resistance to this agent.

PMID- 21876048
TI  - Bovine intestinal bacteria inactivate and degrade ceftiofur and ceftriaxone with
      multiple beta-lactamases.
AB  - The veterinary cephalosporin drug ceftiofur is rapidly degraded in the bovine
      intestinal tract. A cylinder-plate assay was used to detect microbiologically
      active ceftiofur, and high-performance liquid chromatography-mass spectrometry
      analysis was used to quantify the amount of ceftiofur remaining after incubation
      with bovine intestinal anaerobic bacteria, which were isolated from colon
      contents or feces from 8 cattle. Ninety-six percent of the isolates were able to
      inactivate ceftiofur to some degree, and 54% actually degraded the drug. None of
      9 fungal isolates inactivated or degraded ceftiofur. Facultative and obligate
      anaerobic bacterial species that inactivated or degraded ceftiofur were
      identified with Vitek and Biolog systems, respectively. A subset of ceftiofur
      degraders also degraded the chemically similar drug ceftriaxone. Most of the
      species of bacteria that degraded ceftiofur belonged to the genera Bacillus and
      Bacteroides. PCR analysis of bacterial DNA detected specific beta-lactamase
      genes. Bacillus cereus and B. mycoides isolates produced extended-spectrum beta
      lactamases and metallo-beta-lactamases. Seven isolates of Bacteroides spp.
      produced multiple beta-lactamases, including possibly CepA, and metallo-beta
      lactamases. Isolates of Eubacterium biforme, Bifidobacterium breve, and several
      Clostridium spp. also produced ceftiofur-degrading beta-lactamases. An agar gel
      overlay technique on isoelectric focusing separations of bacterial lysates showed
      that beta-lactamase enzymes were sufficient to degrade ceftiofur. These results
      suggest that ceftiofur is inactivated nonenzymatically and degraded enzymatically
      by multiple beta-lactamases from bacteria in the large intestines of cattle.

PMID- 21876049
TI  - Survey of antimicrobial resistance in clinical Burkholderia pseudomallei isolates
      over two decades in Northeast Thailand.
AB  - A 21-year survey conducted in northeast Thailand of antimicrobial resistance to
      parenteral antimicrobial drugs used to treat melioidosis identified 24/4,021
      (0.6%) patients with one or more isolates resistant to ceftazidime (n = 8),
      amoxicillin-clavulanic acid (n = 4), or both drugs (n = 12). Two cases were
      identified at admission, and the remainder were detected a median of 15 days
      after starting antimicrobial therapy. Resistance to carbapenem drugs was not
      detected. These findings support the current prescribing recommendations for
      melioidosis.

PMID- 21876050
TI  - Spider venom peptides for gene therapy of Chlamydia infection.
AB  - Spider venoms are vast natural pharmacopoeias selected by evolution. The venom of
      the ant spider Lachesana tarabaevi contains a wide variety of antimicrobial
      peptides. We tested six of them (latarcins 1, 2a, 3a, 4b, 5, and cytoinsectotoxin
      1a) for their ability to suppress Chlamydia trachomatis infection. HEK293 cells
      were transfected with plasmid vectors harboring the genes of the selected
      peptides. Controlled expression of the transgenes led to a significant decrease
      of C. trachomatis viability inside the infected cells.

PMID- 21876051
TI  - Impact of mutations outside the V3 region on coreceptor tropism phenotypically
      assessed in patients infected with HIV-1 subtype B.
AB  - HIV coreceptor tropism (CTR) testing is a prerequisite for prescribing a
      coreceptor antagonist. CTR is increasingly deduced by analyzing the V3 loop
      sequence of gp120. We investigated the impact of mutations outside V3 on CTR as
      determined by the enhanced-sensitivity Trofile assay (ESTA). Paired ESTA and
      gp120 sequencing (population sequencing; from codon 32 of the conserved C1 to the
      variable V5 domains) were obtained from 60 antiretroviral treatment (ART)-naive
      patients (15 with AIDS) infected with subtype B HIV-1. For gp120 sequence
      analysis, nucleotide mixtures were considered when the second highest
      electropherogram peak was >25%; sequences were translated into all possible
      permutations and classified as X4, dual/mixed (DM), and R5 based on coincident
      ESTA results. ESTA identified R5 and DM viruses in 72 and 28% of patients,
      respectively; no pure X4 was labeled. Forty percent of AIDS patients had R5
      strains. Thirty-two positions, mostly outside V3, were significantly (P < 0.05)
      different between R5 and DM sequences. According to multivariate analysis, amino
      acid changes at 9 and 7 positions within the C1 to C4 and V1 to V5 regions,
      respectively, maintained a statistical significance, as did the net charge of V3
      and C4. When analyzing only R5 sequences, 6 positions in the variable regions
      were found which, along with the V4 net charge, were significantly different for
      sequences from early- and end-stage disease patients. This study identifies
      specific amino acid changes outside V3 which contribute to CTR. Extending the
      analysis to include pure X4 and increasing the sample size would be desirable to
      define gp120 variables/changes which should be included in predictive algorithms.

PMID- 21876052
TI  - Nelfinavir and its active metabolite, hydroxy-t-butylamidenelfinavir (M8), are
      transferred in small quantities to breast milk and do not reach biologically
      significant concentrations in breast-feeding infants whose mothers are taking
      nelfinavir.
AB  - Antiretroviral drugs cross from maternal plasma to breast milk and from breast
      milk to the infant in different concentrations. We measured concentrations of
      nelfinavir and its active metabolite (M8) in maternal plasma and breast milk from
      women and in dried blood spots collected from their infants at delivery and
      postnatal weeks 2, 6, 14, and 24 in the Kisumu Breastfeeding Study, Kisumu,
      Kenya. Nelfinavir-based antiretroviral regimens given to mothers as prevention of
      mother-to-child HIV transmission (PMTCT) do not expose the breast-feeding infant
      to biologically significant concentrations of nelfinavir or M8.

PMID- 21876053
TI  - In vitro activity of antiretroviral drugs against Plasmodium falciparum.
AB  - Malaria and HIV infection are both very common in many developing countries. With
      the increasing availability of therapy for HIV infection, it was of interest to
      determine whether antiretroviral drugs exert antimalarial effects. We therefore
      tested the in vitro activity of 19 antiretroviral drugs against the W2 and 3D7
      strains of Plasmodium falciparum at concentrations up to 50 MUM. None of 5 tested
      nucleoside reverse transcriptase inhibitors demonstrated activity. Two
      nonnucleoside reverse transcriptase inhibitors, efavirenz (mean 50% inhibitory
      concentration [IC(50)] of 22 to 30 MUM against the two strains) and etravirine
      (3.1 to 3.4 MUM), were active; nevirapine was not active. Also active were the
      fusion inhibitor enfuvirtide (6.2 to 7.9 MUM) and the entry inhibitor maraviroc
      (15 to 21 MUM). Raltegravir was not active. However, for all active drugs
      mentioned above, the IC(50)s were considerably greater than the concentrations
      achieved with standard dosing. The effects most likely to be clinically relevant
      were with HIV protease inhibitors. Of the tested compounds, activity was seen
      with lopinavir (2.7 to 2.9 MUM), atazanavir (3.3 to 13.0 MUM), saquinavir (5.0 to
      12.1 MUM), nelfinavir (6.5 to 12.1 MUM), ritonavir (9.5 to 10.9 MUM), tipranavir
      (15.5 to 22.3 MUM), and amprenavir (28.1 to 40.8) but not darunavir. Lopinavir
      was active at levels well below those achieved with standard dosing of
      coformulated lopinavir-ritonavir. Lopinavir also demonstrated modest synergy with
      the antimalarial lumefantrine (mean fractional inhibitory concentration index of
      0.66 for W2 and 0.53 for 3D7). Prior data showed that lopinavir-ritonavir also
      extends the pharmacokinetic exposure of lumefantrine. Thus, when used to treat
      HIV infection, lopinavir-ritonavir may have clinically relevant antimalarial
      activity and also enhance the activity of antimalarials.

PMID- 21876054
TI  - MK-0536 inhibits HIV-1 integrases resistant to raltegravir.
AB  - With the U.S. Food and Drug Administration approval of raltegravir (RAL; MK-0518;
      Merck & Co.), HIV-1 integrase (IN) is the newest therapeutic target for AIDS and
      HIV infections. Recent structural analyses show that IN strand transfer
      inhibitors (INSTIs) share a common binding mode in the enzyme active site. While
      RAL represents a therapeutic breakthrough, the emergence of IN resistance
      mutations imposes the development of new INSTIs. We report here the biochemical
      and antiviral activities of MK-0536, a new IN inhibitor. We demonstrate that,
      like RAL, MK-0536 is highly potent against recombinant IN and viral replication.
      It is also effective against INs that carry the three main RAL resistance
      mutations (Y143R, N155H, and to a lesser extent G140S-Q148H) and against the
      G118R mutant. Modeling of IN developed from recent prototype foamy virus
      structures is presented to account for the differences in the drug activities of
      MK-0536 and RAL against the IN mutants.

PMID- 21876055
TI  - Interrogation of related clinical pan-azole-resistant Aspergillus fumigatus
      strains: G138C, Y431C, and G434C single nucleotide polymorphisms in cyp51A,
      upregulation of cyp51A, and integration and activation of transposon Atf1 in the
      cyp51A promoter.
AB  - Multiple Aspergillus fumigatus isolates from a patient with two aspergillomas
      complicating chronic pulmonary aspergillosis were pan-azole resistant.
      Microsatellite typing was identical for all isolates despite major phenotypic and
      some growth rate differences. Three different cyp51A mutations were found (G138C,
      Y431C, and G434C), of which the first two were demonstrated by heterologous
      expression in a hypersusceptible Saccharomyces cerevisiae strain to be at least
      partly responsible for elevated MICs. cyp51A and cyp51B gene duplication was
      excluded, but increased expression of cyp51A was demonstrated in three isolates
      selected for additional study (7-to 13-fold increases). In the isolate with the
      greatest cyp51A expression, an Aft1 transposon was found inserted 370 bp upstream
      of the start codon of the cyp51A gene, an integration location never previously
      demonstrated in Aspergillus. Two transcription start sites were identified at 49
      and 136 bp upstream of the start codon. The role of the Aft1 transposon, if any,
      in modulating cyp51A expression remains to be established. Increased mRNA
      expression of the transporters AfuMDR1 and AfuMDR4 also was demonstrated in some
      isolates, which could contribute to azole resistance or simply represent a stress
      response. The diversity of confirmed and possible azole resistance mechanisms
      demonstrated in a single series of isogenic isolates is remarkable, indicating
      the ability of A. fumigatus to adapt in the clinical setting.

PMID- 21876056
TI  - Population pharmacokinetics of artemether, lumefantrine, and their respective
      metabolites in Papua New Guinean children with uncomplicated malaria.
AB  - There are sparse published data relating to the pharmacokinetic properties of
      artemether, lumefantrine, and their active metabolites in children, especially
      desbutyl-lumefantrine. We studied 13 Papua New Guinean children aged 5 to 10
      years with uncomplicated malaria who received the six recommended doses of
      artemether (1.7 mg/kg of body weight) plus lumefantrine (10 mg/kg), given with
      fat over 3 days. Intensive blood sampling was carried out over 42 days. Plasma
      artemether, dihydroartemisinin, lumefantrine, and desbutyl-lumefantrine were
      assayed using liquid chromatography-mass spectrometry or high-performance liquid
      chromatography. Multicompartmental pharmacokinetic models for a drug plus its
      metabolite were developed using a population approach that included plasma
      artemether and dihydroartemisinin concentrations below the limit of quantitation.
      Although artemether bioavailability was variable and its clearance increased by
      67.8% with each dose, the median areas under the plasma concentration-time curve
      from 0 h to infinity (AUC(0-infinity)s) for artemether and dihydroartemisinin
      (3,063 and 2,839 MUg . h/liter, respectively) were similar to those reported
      previously in adults with malaria. For lumefantrine, the median AUC(0-infinity)
      (459,980 MUg . h/liter) was also similar to that in adults with malaria. These
      data support the higher dose recommended for children weighing 15 to 35 kg (35%
      higher than that for a 50-kg adult) but question the recommendation for a lower
      dose in children weighing 12.5 to 15 kg. The median desbutyl
      lumefantrine/lumefantrine ratio in the children in our study was 1.13%, within
      the range reported for adults and higher at later time points because of the
      longer desbutyl-lumefantrine terminal elimination half-life. A combined desbutyl
      lumefantrine and lumefantrine AUC(0-infinity) weighted on in vitro antimalarial
      activity was inversely associated with recurrent parasitemia, suggesting that
      both the parent drug and the metabolite contribute to the treatment outcome of
      artemether-lumefantrine.

PMID- 21876057
TI  - Clinical carbapenem-resistant Acinetobacter baylyi strain coharboring blaSIM-1
      and blaOXA-23 from China.
AB  - bla(SIM-1) and bla(OXA-23) were codetected in clinical carbapenem-resistant
      Acinetobacter baylyi strain NB09A30. Both of carbapenemase genes were located on
      a large plasmid (ca. 360 kb). bla(SIM-1) was found as a gene cassette inserted
      into a class 1 integron identical to that determined in Acinetobacter sp.
      isolates from South Korea. The genetic structure of bla(OXA-23) in NB09A30 was
      different from that in the prevalent Acinetobacter baumannii of clonal complex 92
      (CC92) from the same hospital.

PMID- 21876058
TI  - Clinically relevant plasma concentrations of colistin in combination with
      imipenem enhance pharmacodynamic activity against multidrug-resistant Pseudomonas
      aeruginosa at multiple inocula.
AB  - The use of combination antibiotic therapy may be beneficial against rapidly
      emerging resistance in Pseudomonas aeruginosa. The aim of this study was to
      systematically investigate in vitro bacterial killing and resistance emergence
      with colistin alone and in combination with imipenem against multidrug-resistant
      (MDR) P. aeruginosa. Time-kill studies were conducted over 48 h using 5 clinical
      isolates and ATCC 27853 at two inocula (~10(6) and ~10(8) CFU/ml); MDR, non-MDR,
      and colistin-heteroresistant and -resistant strains were included. Nine colistin
      imipenem combinations were investigated. Microbiological response was examined by
      log changes at 6, 24, and 48 h. Colistin combined with imipenem at clinically
      relevant concentrations increased the levels of killing of MDR and colistin
      heteroresistant isolates at both inocula. Substantial improvements in activity
      with combinations were observed across 48 h with all colistin concentrations at
      the low inoculum and with colistin at 4* and 16* MIC (or 4 and 32 mg/liter) at
      the high inoculum. Combinations were additive or synergistic against imipenem
      resistant isolates (MICs, 16 and 32 mg/liter) at the 10(6)-CFU inoculum in 9, 11,
      and 12 of 18 cases (i.e., 9 combinations across 2 isolates) at 6, 24, and 48 h,
      respectively, and against the same isolates at the 10(8)-CFU inoculum in 11, 7,
      and 8 cases, respectively. Against a colistin-resistant strain (MIC, 128
      mg/liter), combinations were additive or synergistic in 9 and 8 of 9 cases at 24
      h at the 10(6)- and 10(8)-CFU inocula, respectively, and in 5 and 7 cases at 48
      h. This systematic study provides important information for optimization of
      colistin-imipenem combinations targeting both colistin-susceptible and colistin
      resistant subpopulations.

PMID- 21876061
TI  - Fractal geometry and the pharmacometrics of micafungin in overweight, obese, and
      extremely obese people.
AB  - The majority of Americans are overweight, and the incidence of obesity continues
      to increase. This trend predisposes people to a number of deleterious
      consequences, including the metabolic syndrome and other conditions that lead to
      a greater number of hospital admissions. Invasive candidiasis is an important
      nosocomial infection that results from these admissions. Echinocandins such as
      micafungin are indicated for treatment. We have previously demonstrated that
      overweight patients exhibit higher micafungin systemic clearance (SCL) than
      leaner patients. We hypothesized that obese and extremely obese people would show
      even higher SCL than merely overweight patients. To test this, we performed a
      prospective study of 36 adult volunteers randomized to receive a single dose of
      either 100 mg or 300 mg of micafungin whose body mass index fell within one of
      the following categories: <25, 25 to 40, and >40 kg/m(2). The male-to-female
      ratio was 1:1. The minimum weight was 43 kg, the median 97 kg, and the maximum
      weight 155 kg. A two-compartment model was examined using the maximum likelihood
      solution via the expectation-maximization algorithm. Men had a higher median SCL
      of 1.53 liters/h versus 1.29 liters/h (P = 0.01) in the Mann-Whitney U-test. The
      typical SCL was 1.04 liters/h but increased by a factor of (weight/66)(0.75) as
      weight increased above 66 kg. Thus, the relationship between micafungin SCL and
      weight in adults is best described by fractal-geometry-based laws. Furthermore,
      micafungin SCL continues to increase as weight increases, with no obvious
      plateau. This leads to a requirement for strategies to determine individualized
      dosing levels for obese and extremely obese patients.

PMID- 21876060
TI  - SMB-1, a novel subclass B3 metallo-beta-lactamase, associated with ISCR1 and a
      class 1 integron, from a carbapenem-resistant Serratia marcescens clinical
      isolate.
AB  - A carbapenem-resistant Serratia marcescens strain, 10mdr148, was identified in a
      Japanese hospital in 2010. The carbapenem resistance of this strain was
      attributed to the production of a novel metallo-beta-lactamase (MBL), named SMB-1
      (Serratia metallo-beta-lactamase). SMB-1 possessed a zinc binding motif,
      H(Q)XHXDH (residues 116 to 121), H196, and H263 and was categorized as a member
      of subclass B3 MBL. SMB-1 has 75% amino acid identity with the most closely
      related MBL, AMO1, of uncultured bacterium, recently identified through the
      metagenomic analysis of apple orchard soil. The introduction of bla(SMB-1) into
      Escherichia coli conferred resistance to a variety of beta-lactam antibiotics,
      penicillins, cephalosporins, and carbapenems, but not aztreonam, a resistance
      pattern consistent with those of other MBLs. SMB-1 demonstrated high k(cat)
      values of >500 s(-1) for carbapenems, resulting in the highest hydrolyzing
      efficiency (k(cat)/K(m)) among the agents tested. The hydrolyzing activity of SMB
      1 was well inhibited by chelating agents. The bla(SMB-1) gene was located on the
      chromosome of S. marcescens strain 10mdr148 and at the 3' end of the ISCR1
      element in complex with a typical class 1 integron carrying aac(6')-Ib and catB3
      gene cassettes. Downstream of bla(SMB-1), the second copy of the 3'conserved
      segment and ISCR1 were found. To our knowledge, this is the first subclass B3 MBL
      gene associated with an ISCR1 element identified in an Enterobacteriaceae
      clinical isolate. A variety of antibiotic resistance genes embedded with ISCR1
      have been widely spread among Enterobacteriaceae clinical isolates, thus the
      further dissemination of bla(SMB-1) mediated by ISCR1 transposition activity may
      become a future concern.

PMID- 21876059
TI  - Current prospects for the fluoroquinolones as first-line tuberculosis therapy.
AB  - While fluoroquinolones (FQs) have been successful in helping cure multidrug
      resistant tuberculosis (MDR TB), studies in mice have suggested that if used as
      first-line agents they might reduce the duration of therapy required to cure drug
      sensitive TB. The results of phase II trials with FQs as first-line agents have
      been mixed, but in at least three studies where moxifloxacin substituted for
      ethambutol, there was an increase in the early percentage of sputa that converted
      to negative for bacilli. Phase III trials are in progress to test the
      effectiveness of 4-month FQ-containing regimens, but there is concern that the
      widespread use of FQs for other infections could engender a high prevalence of FQ
      resistant TB. However, several studies suggest that despite wide FQ use, the
      prevalence of FQ-resistant TB is low, and the majority of the resistance is low
      level. The principal risk for resistance may be when FQs are used to treat
      nonspecific respiratory symptoms that are in fact TB, so curtailing this use of
      FQs could reduce the development of resistance and also the delays in TB
      diagnosis and treatment that have been documented when an FQ is given in this
      setting. While the future of FQs as first-line therapy will likely depend upon
      the results of the ongoing phase III trials, if they are to be effectively
      employed in high-TB-burden regions their use for community-acquired pneumonias
      should be restricted, the prevalence of FQ-resistant TB should be monitored, and
      the cost of the treatment should be comparable to that of current standard drug
      regimens.

PMID- 21876062
TI  - Pyrazinoic acid decreases the proton motive force, respiratory ATP synthesis
      activity, and cellular ATP levels.
AB  - Pyrazinoic acid, the active form of the first-line antituberculosis drug
      pyrazinamide, decreased the proton motive force and respiratory ATP synthesis
      rates in subcellular mycobacterial membrane assays. Pyrazinoic acid also
      significantly lowered cellular ATP levels in Mycobacterium bovis BCG. These
      results indicate that the predominant mechanism of killing by this drug may
      operate by depletion of cellular ATP reserves.

PMID- 21876063
TI  - Survival of adhering staphylococci during exposure to a quaternary ammonium
      compound evaluated by using atomic force microscopy imaging.
AB  - Effects of a quaternary ammonium compound (QAC) on the survival of adhering
      staphylococci on a surface were investigated using atomic force microscopy (AFM).
      Four strains with different minimal inhibitory concentrations (MIC) and minimal
      bactericidal concentrations (MBC) for the QAC were exposed to three different
      concentrations of the QAC in potassium phosphate buffer (0.5*, 1*, and 2* MBC)
      while adhering to glass. Adhering staphylococci were repeatedly imaged with AFM
      in the contact mode, and the cell surface was found to wrinkle upon progressive
      exposure to the QAC until bacteria disappeared from the substratum. Higher
      concentrations of QAC yielded faster wrinkling and the disappearance of bacteria
      during imaging. Two slime-producing staphylococcal strains survived longer on the
      surface than two non-slime-producing strains despite similar MICs and MBCs. All
      staphylococci adhering in unscanned areas remained adhering during exposure to
      QAC. Since MICs and MBCs did not relate to bacterial cell surface
      hydrophobicities and zeta potentials, survival on the surface is probably not
      determined by the direct interaction of QAC molecules with the cell surface.
      Instead, it is suggested that the pressure of the AFM tip assists the
      incorporation of QAC molecules in the membrane and enhances their bactericidal
      efficacy. In addition, the prolonged survival under pressure from slime-producing
      strains on a surface may point to a new protective role of slime as a stress
      absorber, impeding the incorporation of QAC molecules. The addition of Ca(2+)
      ions to a QAC solution yielded longer survival of intact, adhering staphylococci,
      suggesting that Ca(2+) ions can impede the exchange of membrane Ca(2+) ions
      required for QAC incorporation.

PMID- 21876064
TI  - Occurrence of the carbapenem-hydrolyzing beta-lactamase gene blaOXA-48 in the
      environment in Morocco.

PMID- 21876065
TI  - Biochemical characterization of Sfh-I, a subclass B2 metallo-beta-lactamase from
      Serratia fonticola UTAD54.
AB  - The subclass B2 metallo-beta-lactamase (MBL) Sfh-I from Serratia fonticola UTAD54
      was cloned and overexpressed in Escherichia coli. The recombinant protein binds
      one equivalent of zinc, as shown by mass spectrometry, and preferentially
      hydrolyzes carbapenem substrates. However, compared to other B2 MBLs, Sfh-I also
      shows limited hydrolytic activity against some additional substrates and is not
      inhibited by a second equivalent of zinc. These data confirm Sfh-I to be a
      subclass B2 metallo-beta-lactamase with some distinctive properties.

PMID- 21876066
TI  - A long-term open-label extension study assessing cognition and behavior,
      tolerability, safety, and efficacy of adjunctive levetiracetam in children aged 4
      to 16 years with partial-onset seizures.
AB  - The objective of this study was to assess cognition and behavior in children (4
      16 years; n = 103) with partial-onset seizures using the Leiter-R International
      Performance Scale and Achenbach Child Behavior Checklist. The study was a
      multicenter, open-label, noncomparative 48-week extension study (NCT00152516) of
      adjunctive levetiracetam (20-100 mg/kg/d, mean 50.2 mg/kg/d). Improvement from
      baseline in Leiter-R Memory Screen composite score at weeks 24 and 48 (mean [SD]
      change, +4.8 [12.6] and +4.5 [15.3]) was similar to changes observed with
      levetiracetam and placebo in a prior study. Child Behavior Checklist Syndrome
      scores improved from baseline at weeks 24 and 48 (total problems mean [SD]
      change, -9.3 [22.2] and -10.4 [23.4]). Adjunctive levetiracetam was well
      tolerated (most frequently reported central nervous system-related treatment
      emergent adverse events: headache [24.3%], aggression [7.8%], irritability
      [7.8%]). Of the patients, 4.9% discontinued because of treatment-emergent adverse
      events. Levetiracetam provided good and sustained seizure control (median
      percentage reduction from baseline in partial-onset seizure frequency/wk during
      maintenance: 86.4%); 24.7% of patients had continuous seizure freedom from all
      seizure types for >=40 weeks. In children, adjunctive levetiracetam was
      associated with long-term stability in cognitive functioning and improvement in
      emotional/behavioral functioning over time.

PMID- 21876067
TI  - Effect of chronic iron deficiency on neuropsychological domains in infants.
AB  - The aim of this study was to assess the effects of chronic iron deficiency on
      neuropsychological traits in infants. We established the nutritional iron status
      and assessed the neuropsychological characteristics of 58 Mexican 14- to 18-month
      old infants. The Bayley Scales of Infant Development, preschool language scales
      and an environmental sound perception task designed expressly for the study, were
      used. The infants' mothers were asked to fill out 2 questionnaires concerning
      their child's sociodemographic background. Six different neuropsychological
      domains were analyzed. Results showed that the chronic iron deficiency group did
      show significantly lower scores on language, environmental sound perception, and
      motor measures, when compared with infants with normal nutritional iron status at
      6 and 14 to 18 months. Our conclusion is that the development of language and
      motor skills and environmental sound perception appeared to be sensitive to the
      effects of chronic iron deficiency in infants.

PMID- 21876069
TI  - Prevalence and characteristics of familial hyperaldosteronism: the PATOGEN study
      (Primary Aldosteronism in TOrino-GENetic forms).
AB  - Primary aldosteronism (PA) is the most frequent cause of secondary hypertension,
      and patients display an increased prevalence of cardiovascular events compared
      with essential hypertensives. To date, 3 familial forms of PA have been described
      and termed familial hyperaldosteronism types I, II, and III (FH-I to -III). The
      aim of this study was to investigate the prevalence and clinical characteristics
      of the 3 forms of FH in a large population of PA patients. Three-hundred
      consecutive PA patients diagnosed in our unit were tested by long-PCR of the
      CYP11B1/CYP11B2 hybrid gene that causes FH-I, and all of the available relatives
      of PA patients were screened to confirm or exclude PA and, thus, FH-II. Urinary
      18-hydroxycortisol and 18-oxocortisol were measured in all of the familial PA
      patients. Two patients were diagnosed with FH-I (prevalence: 0.66%), as well as
      21 of their relatives, and clinical phenotypes of the 2 affected families varied
      markedly. After exclusion of families who refused testing and those who were not
      informative, 199 families were investigated, of which 12 were diagnosed with FH
      II (6%) and an additional 15 individuals had confirmed PA; clinical and
      biochemical phenotypes of FH-II families were not significantly different from
      sporadic PA patients. None of the families displayed a phenotype compatible with
      FH-III diagnosis. Our study demonstrates that familial forms of
      hyperaldosteronism are more frequent than previously expected and reinforces the
      recommendation of the Endocrine Society Guidelines to screen all first-degree
      hypertensive relatives of PA patients.

PMID- 21876068
TI  - Disease progression in a mouse model of amyotrophic lateral sclerosis: the
      influence of chronic stress and corticosterone.
AB  - Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease
      characterized by motor neuron cell loss, muscular atrophy, and a shortened life
      span. Survival is highly variable, as some patients die within months, while
      others live for many years. Exposure to stress or the development of a nonoptimal
      stress response to disease might account for some of this variability. We show in
      the SOD1(G93A) mouse model of ALS that recurrent exposure to restraint stress led
      to an earlier onset of astrogliosis and microglial activation within the spinal
      cord, accelerated muscular weakness, and a significant decrease in median
      survival (105 vs. 122 d) when compared to nonstressed animals. Moreover, during
      normal disease course, ALS mice display a cacostatic stress response by
      developing an aberrant serum corticosterone circadian rhythm. Interestingly, we
      also found that higher corticosterone levels were significantly correlated with
      both an earlier onset of paralysis (males: r(2)=0.746; females: r(2)=0.707) and
      shorter survival times (males: r(2)=0.680; females: r(2)=0.552) in ALS mice.
      These results suggest that stress is capable of accelerating disease progression
      and that strategies that modulate glucocorticoid metabolism might be a viable
      treatment approach for ALS.

PMID- 21876070
TI  - Disruption of K(2P)6.1 produces vascular dysfunction and hypertension in mice.
AB  - K(2P)6.1, a member of the 2-pore domain K channel family, is highly expressed in
      the vascular system; however, its function is unknown. We tested the following
      hypotheses. K(2P)6.1 regulates the following: (1) systemic blood pressure; (2)
      the contractile state of arteries; (3) vascular smooth muscle cell migration; (4)
      proliferation; and/or (5) volume regulation. Mice lacking K(2P)6.1 (KO) were
      generated by deleting exon 1 of Kcnk6. Mean arterial blood pressure in both
      anesthetized and awake KO mice was increased by 17+/-2 and 26+/-3 mm Hg,
      respectively (P<0.05). The resting membrane potential in freshly dispersed
      vascular smooth muscle cells was depolarized by 17+/-2 mV in the KO compared with
      wild-type littermates (P<0.05). The contractile responses to KCl (P<0.05) and BAY
      K 8644 (P<0.01), an activator of L-type calcium channels, were enhanced in
      isolated segments of aorta from KO mice. However, there was no difference in the
      current density of L-type calcium channels. Responses to U46619, an agent that
      activates rho kinase, showed an enhanced contraction in aorta from KO mice
      (P<0.001). The BAY K 8644-mediated increase in contraction was decreased to wild
      type levels when treated with Y27632, a rho kinase inhibitor, (P<0.05). K(2P)6.1
      does not appear to be involved with migration, proliferation, or volume
      regulation in cultured vascular smooth muscle cells. We conclude that K(2P)6.1
      deficiency induces vascular dysfunction and hypertension through a mechanism that
      may involve smooth muscle cell depolarization and enhanced rho kinase activity.

PMID- 21876071
TI  - High-dose treatment with telmisartan induces monocytic peroxisome proliferator
      activated receptor-gamma target genes in patients with the metabolic syndrome.
AB  - The present study aimed to explore the anti-inflammatory effects and peroxisome
      proliferator-activated receptor-gamma (PPARgamma)-activating properties of the
      angiotensin type 1 receptor blocker telmisartan by analysis of serum interleukin
      6 levels and monocytic PPARgamma target gene expression in drug-naive patients
      with the metabolic syndrome. This was a 14-week, randomized, double-blind,
      placebo-controlled 2-center study with telmisartan 80 mg/d and telmisartan 160
      mg/d in 54 patients with the metabolic syndrome. In addition to clinical
      laboratory measurements, peripheral monocytes were extracted by negative
      isolation using a Dynal Monocyte kit to evaluate ligand-activated PPARgamma
      target gene expression (CD36 and CD163) at baseline and study end using
      quantitative real-time RT-PCR. In this low-risk patient population, telmisartan
      (80 and 160 mg) treatment did not significantly affect serum interleukin 6
      levels. Expression of the PPARgamma target gene CD36 in monocytes was markedly
      induced by telmisartan from baseline to study end (telmisartan 80 mg: 2.3+/-1.5
      fold change versus placebo [P value not significant]; telmisartan 160 mg: 3.5+/
      0.9-fold change versus placebo [P<0.05]). The recently reported PPARgamma target
      gene CD163 was slightly induced by telmisartan (telmisartan 80 mg: 1.1+/-0.3-fold
      change versus placebo [P value not significant]; telmisartan 160 mg: 1.4+/-0.4
      fold change versus placebo [P value not significant]), which did not reach
      statistical significance. This is the first clinical description of monocytic
      PPARgamma target gene regulation with high-dose telmisartan treatment. These data
      implicate that the angiotensin type 1 receptor blocker telmisartan activates
      PPARgamma in circulating monocytes of patients with the metabolic syndrome.

PMID- 21876073
TI  - Two-pore domain K+ channels: evidence for TWIK-2 in blood pressure regulation.

PMID- 21876072
TI  - Decreased slow wave sleep increases risk of developing hypertension in elderly
      men.
AB  - The importance of sleep to health and cardiovascular disease has become
      increasingly apparent. Sleep-disordered breathing, sleep duration, and sleep
      architecture may all influence metabolism and neurohormonal systems, yet no
      previous study has evaluated these sleep characteristics concurrently in relation
      to incident hypertension. Our objective was to determine whether incident
      hypertension is associated with polysomnography measures of sleep-disordered
      breathing, sleep duration, and sleep architecture in older men. Participants were
      784 community-dwelling, ambulatory men >=65 years of age (mean age: 75.1+/-4.9
      years) from the Outcomes of Sleep Disorders in Older Men Study who did not have
      hypertension at the time of their in-home polysomnography sleep studies (2003
      2005) and who returned for follow-up (2007-2009). Of 784 older men included in
      this report, 243 met criteria for incident hypertension after a mean follow-up of
      3.4 years. In unadjusted analyses, incident hypertension was associated with
      increased hypoxemia, increased sleep stages N1 and N2, and decreased stage N3
      (slow wave sleep [SWS]). After adjustment for age, nonwhite race, study site, and
      body mass index, the only sleep index to remain significantly associated with
      incident hypertension was SWS percentage (odds ratio for lowest to highest
      quartile of SWS: 1.83 [95% CI: 1.18 to 2.85]). No attenuation of this association
      was seen after accounting for sleep duration, sleep fragmentation, and indices of
      sleep-disordered breathing. Percentage time in SWS was inversely associated with
      incident hypertension, independent of sleep duration and fragmentation, and sleep
      disordered breathing. Selective deprivation of SWS may contribute to adverse
      blood pressure in older men.

PMID- 21876074
TI  - Uric acid: a clinically useful marker to distinguish preeclampsia from
      gestational hypertension.

PMID- 21876075
TI  - Prognostic significance of serum uric acid in women with gestational
      hypertension.
AB  - Aim of our study was to ascertain, prospectively, whether serum uric acid is a
      suitable predictor of preeclampsia and/or the delivery of small-for-gestational
      age infants in women with gestational hypertension. We screened 206 primiparas,
      with a singleton pregnancy, referred for recent onset of hypertension. At
      presentation, we measured serum uric acid, creatinine, blood glucose, hemoglobin
      and platelet level, and 24-hour proteinuria, as well as office and 24-hour blood
      pressures. We followed the women until 1 month after delivery and recorded
      pregnancy outcome. After logistic regression analysis, uric acid resulted a
      significant predictor of preeclampsia, with an unadjusted odds ratio of 9.1 (95%
      CI: 4.8 to 17.4; P<0.001); after adjustment for age, gestation week, hemoglobin
      and platelet levels, serum creatinine, office and 24-hour average systolic and
      diastolic blood pressures, it was 7.1 (95% CI: 3.2 to 15.7; P<0.001). Regarding
      the association between maternal serum uric acid and the chance of giving birth
      to a small-for-gestational-age infant, the unadjusted odds ratio was 1.7 (95% CI:
      1.4 to 2.2; P<0.001), and it was 1.6 (95% CI: 1.1 to 2.4; P=0.02) after
      adjustment. Receiver operating characteristic analysis showed that serum uric
      acid, at a 309-MUmol/L cutoff, predicted the development of preeclampsia (area
      under the curve: 0.955), with 87.7% sensitivity and 93.3% specificity, and the
      delivery of small-for-gestational-age infants (area under the curve: 0.784) with
      83.7% sensitivity and 71.7% specificity. In conclusion, the results of our study
      show that serum uric acid is a reliable predictor of preeclampsia in women
      referred for gestational hypertension.

PMID- 21876077
TI  - Long-term risk of colorectal cancer after negative colonoscopy.
AB  - PURPOSE: Colonoscopy is thought to be a powerful and cost-effective tool to
      reduce colorectal cancer (CRC) incidence and mortality. Empirical evidence for
      overall and risk group-specific definition of screening intervals is sparse. We
      aimed to assess the risk of CRC according to time since negative colonoscopy,
      overall, and by sex, smoking, and family history of CRC, in a large population
      based case-control study. PATIENTS AND METHODS: In all, 1,945 patients with CRC
      and 2,399 population controls were recruited in 22 hospitals and through
      population registers in the Rhine-Neckar region of Germany from 2003 to 2007.
      Data on history of colonoscopy and important covariates were obtained by personal
      interviews and from medical records. RESULTS: Compared with people who had never
      undergone colonoscopy, people with a previous negative colonoscopy had a strongly
      reduced risk of CRC. Adjusted odds ratios for time windows of 1 to 2, 3 to 4, 5
      to 9, 10 to 19, and 20+ years after negative colonoscopy were 0.14 (95% CI, 0.10
      to 0.20), 0.12 (95% CI, 0.08 to 0.19), 0.26 (95% CI, 0.18 to 0.39), 0.28 (95% CI,
      0.17 to 0.45), and 0.40 (95% CI, 0.24 to 0.66), respectively. Low risks even
      beyond 10 years after negative colonoscopy were observed for both left- and right
      sided CRC and in all risk groups assessed except current smokers, who had a risk
      similar to that of never smokers with no previous colonoscopy 10 or more years
      after a negative colonoscopy. CONCLUSION: These results support suggestions that
      screening intervals for CRC screening by colonoscopy could be longer than the
      commonly recommended 10 years in most cases, perhaps even among men and people
      with a family history of CRC, but probably not among current smokers.

PMID- 21876076
TI  - Early life stress enhances angiotensin II-mediated vasoconstriction by reduced
      endothelial nitric oxide buffering capacity.
AB  - We reported previously that maternal separation (MS) sensitizes adult rats to
      angiotensin II (Ang II)-induced hypertension. The aim of this study was to
      investigate the vascular reactivity to Ang II and the role of renin-angiotensin
      system components, reactive oxygen species production, and NO synthase (NOS)
      buffering capacity mediating the exacerbated Ang II-induced responses. MS rats
      were separated from their mothers for 3 h/d from days 2 to 14 of life. Controls
      were nonhandled littermates. At 12 weeks of age, aortic Ang II-induced
      constriction was greater from MS rats compared with controls (P<0.05); moreover,
      endothelial denudation abolished this difference. The response to other
      constrictors was unchanged. Angiotensin type 2 receptor function was reduced in
      aortic Ang II-induced constriction from MS rats compared with controls.
      Angiotensin type 1 receptor function was similarly abolished in both groups.
      However, protein expressions of angiotensin type 1 and angiotensin type 2
      receptors were similar in aortic rings from MS and control rats. Preincubation
      with superoxide inhibitor or scavenger attenuated the Ang II-induced
      vasoconstriction in control but not in MS rats. However, acute preincubation with
      an NOS inhibitor enhanced aortic Ang II-induced constriction in aorta from
      control rats, but this effect was significantly reduced in MS rats compared with
      control rats. Accordingly, a further increase in Ang II-induced hypertension
      attributed to chronic NOS inhibition (days 10 to 13) was blunted in MS rats
      compared with control rats. Similar NOS expression and activity were observed in
      control and MS rats. In conclusion, MS induces a phenotype with reduced
      endothelial NOS buffering capacity leading to dysfunctional endothelial Ang II
      mediated signaling and sensitization to Ang II-induced vasoconstriction.

PMID- 21876078
TI  - Squamous cell carcinoma of the bulbar urethra.

PMID- 21876079
TI  - Chek2 DNA damage response pathway and inherited breast cancer risk.

PMID- 21876080
TI  - Testing epidermal growth factor receptor mutations in patients with non-small
      cell lung cancer to choose chemotherapy: the other side of the coin.

PMID- 21876081
TI  - Association between vitamin D and risk of colorectal cancer: a systematic review
      of prospective studies.
AB  - PURPOSE: To conduct a systematic review of prospective studies assessing the
      association of vitamin D intake or blood levels of 25-hydroxyvitamin D [25(OH)D]
      with the risk of colorectal cancer using meta-analysis. METHODS: Relevant studies
      were identified by a search of MEDLINE and EMBASE databases before October 2010
      with no restrictions. We included prospective studies that reported relative risk
      (RR) estimates with 95% CIs for the association between vitamin D intake or blood
      25(OH)D levels and the risk of colorectal, colon, or rectal cancer. Approximately
      1,000,000 participants from several countries were included in this analysis.
      RESULTS: Nine studies on vitamin D intake and nine studies on blood 25(OH)D
      levels were included in the meta-analysis. The pooled RRs of colorectal cancer
      for the highest versus lowest categories of vitamin D intake and blood 25(OH)D
      levels were 0.88 (95% CI, 0.80 to 0.96) and 0.67 (95% CI, 0.54 to 0.80),
      respectively. There was no heterogeneity among studies of vitamin D intake (P =
      .19) or among studies of blood 25(OH)D levels (P = .96). A 10 ng/mL increment in
      blood 25(OH)D level conferred an RR of 0.74 (95% CI, 0.63 to 0.89). CONCLUSION:
      Vitamin D intake and blood 25(OH)D levels were inversely associated with the risk
      of colorectal cancer in this meta-analysis.

PMID- 21876082
TI  - Matrix metalloproteinase-3 producing diffuse large B-cell lymphoma, not otherwise
      specified associated with rheumatoid arthritis.

PMID- 21876083
TI  - Risk of breast cancer in women with a CHEK2 mutation with and without a family
      history of breast cancer.
AB  - PURPOSE: To estimate the risk of breast cancer in a woman who has a CHEK2
      mutation depending on her family history of breast cancer. PATIENTS AND METHODS:
      Seven thousand four hundred ninety-four BRCA1 mutation-negative patients with
      breast cancer and 4,346 control women were genotyped for four founder mutations
      in CHEK2 (del5395, IVS2+1G>A, 1100delC, and I157T). RESULTS: A truncating
      mutation (IVS2+1G>A, 1100delC, or del5395) was present in 227 patients (3.0%) and
      in 37 female controls (0.8%; odds ratio [OR], 3.6; 95% CI, 2.6 to 5.1). The OR
      was higher for women with a first- or second-degree relative with breast cancer
      (OR, 5.0; 95% CI, 3.3 to 7.6) than for women with no family history (OR, 3.3; 95%
      CI, 2.3 to 4.7). If both a first- and second-degree relative were affected with
      breast cancer, the OR was 7.3 (95% CI, 3.2 to 16.8). Assuming a baseline risk of
      6%, we estimate the lifetime risks for carriers of CHEK2 truncating mutations to
      be 20% for a woman with no affected relative, 28% for a woman with one second
      degree relative affected, 34% for a woman with one first-degree relative
      affected, and 44% for a woman with both a first- and second-degree relative
      affected. CONCLUSION: CHEK2 mutation screening detects a clinically meaningful
      risk of breast cancer and should be considered in all women with a family history
      of breast cancer. Women with a truncating mutation in CHEK2 and a positive family
      history of breast cancer have a lifetime risk of breast cancer of greater than
      25% and are candidates for magnetic resonance imaging screening and for tamoxifen
      chemoprevention.

PMID- 21876084
TI  - Magnetic resonance imaging-detected tumor response for locally advanced rectal
      cancer predicts survival outcomes: MERCURY experience.
AB  - PURPOSE: To assess magnetic resonance imaging (MRI) and pathologic staging after
      neoadjuvant therapy for rectal cancer in a prospectively enrolled, multicenter
      study. METHODS: In a prospective cohort study, 111 patients who had rectal cancer
      treated by neoadjuvant therapy were assessed for response by MRI and pathology
      staging by T, N and circumferential resection margin (CRM) status. Tumor
      regression grade (TRG) was also assessed by MRI. Overall survival (OS) was
      estimated by using the Kaplan-Meier product-limit method, and Cox proportional
      hazards models were used to determine associations between staging of good and
      poor responders on MRI or pathology and survival outcomes after controlling for
      patient characteristics. RESULTS: On multivariate analysis, the MRI-assessed TRG
      (mrTRG) hazard ratios (HRs) were independently significant for survival (HR,
      4.40; 95% CI, 1.65 to 11.7) and disease-free survival (DFS; HR, 3.28; 95% CI,
      1.22 to 8.80). Five-year survival for poor mrTRG was 27% versus 72% (P = .001),
      and DFS for poor mrTRG was 31% versus 64% (P = .007). Preoperative MRI-predicted
      CRM independently predicted local recurrence (LR; HR, 4.25; 95% CI, 1.45 to
      12.51). Five-year survival for poor post-treatment pathologic T stage (ypT) was
      39% versus 76% (P = .001); DFS for the same was 38% versus 84% (P = .001); and LR
      for the same was 27% versus 6% (P = .018). The 5-year survival for involved pCRM
      was 30% versus 59% (P = .001); DFS, 28 versus 62% (P = .02); and LR, 56% versus
      10% (P = .001). Pathology node status did not predict outcomes. CONCLUSION: MRI
      assessment of TRG and CRM are imaging markers that predict survival outcomes for
      good and poor responders and provide an opportunity for the multidisciplinary
      team to offer additional treatment options before planning definitive surgery.
      Postoperative histopathology assessment of ypT and CRM but not post-treatment N
      status were important postsurgical predictors of outcome.

PMID- 21876085
TI  - Risk of second malignant neoplasm among patients with lymphoma.

PMID- 21876086
TI  - Placental morphologic features and chorionic surface vasculature at term are
      highly correlated with 3-dimensional sonographic measurements at 11 to 14 weeks.
AB  - OBJECTIVES: The purpose of this study was to examine the potential for 3
      dimensional sonographic measurement of the early placenta in predicting ultimate
      placental morphologic features at delivery. METHODS: In this prospective cohort
      study, we collected 3-dimensional sonographic volume sets of placentas at 11 to
      14 weeks and then collected the placentas after delivery. The sonographic data
      were manipulated to obtain various novel measurements of early gross placental
      morphologic features and the umbilical cord insertion location. The placental
      weight, chorionic plate area, cord location, and mean chorionic vascular density
      were obtained from the delivered postpartum placentas. Analyses were performed to
      identify potential early placental characteristics that were correlated with the
      ultimate placental morphologic features. The placental weight, cord marginality,
      and mean chorionic vascular density served as the outcome measures of interest.
      RESULTS: Measurements of the early placental volume correlated with the delivered
      placental weight. An irregular early placental shape, as measured by sonography,
      was significantly inversely correlated with placental weight (P < .05). The
      placental morphologic index, a measure of a flatter placenta, was inversely
      correlated with both the placental weight and chorionic plate area, possibly
      indicating the importance of placental thickness even in the first trimester
      before villous arborization. In addition, early sonographic measures of the
      location of the umbilical cord insertion were significantly correlated with the
      ultimate marginality of the cord insertion as well as the mean chorionic vascular
      density (P < .05). CONCLUSIONS: Many important ultimate placental morphologic
      features are likely predetermined early in pregnancy. Three-dimensional
      sonography may play an increasing role in the in utero evaluation of the early
      placenta.

PMID- 21876088
TI  - Reference intervals for fetal ear length between 19 and 24 weeks of pregnancy on
      3-dimensional sonography.
AB  - OBJECTIVES: The purpose of this study was to establish reference intervals for
      fetal ear length using 3-dimensional sonography in the rendering mode. METHODS: A
      cross-sectional study was conducted on 114 women from 19 weeks to 23 weeks 6 days
      of normal pregnancy. Fetal ear length measurement was performed in the rendering
      mode, obtained from 2-dimensional mode reconstruction. To determine the
      correlation between ear length and gestational age, scatterplots were
      constructed, and the Pearson correlation coefficient was calculated. Mean,
      median, SD, maximum, and minimum values and percentiles for each gestational age
      were calculated. To calculate the intraobserver reproducibility, we used the
      intraclass correlation coefficient. RESULTS: The mean ear length +/- SD increased
      from 14.43 +/- 1.28 mm (range, 12.80-16.50 mm) in the 19th week of pregnancy to
      19.72 +/- 1.87 mm (range, 17.20-22.40 mm) in the 23rd week. Three-dimensional
      sonographic ear length measurements were correlated with gestational age, with
      the best adjustment represented by the following exponential equation: ear length
      = exp(1.215 * gestational age - 8.692) (R(2) = 0.423). The intraobserver
      reproducibility was excellent, resulting in an intraclass correlation coefficient
      of 0.967 (95% confidence interval, 0.939-0.982). CONCLUSIONS: Reference intervals
      for fetal ear length using 3-dimensional sonography in the rendering mode from 19
      weeks to 23 weeks 6 days of pregnancy were determined and proved reproducible.

PMID- 21876087
TI  - Fertility performance and obstetric outcomes among women with previous cesarean
      scar pregnancy.
AB  - OBJECTIVES: The purpose of this study was to assess fertility performance and
      obstetric outcomes after treatment of cesarean scar pregnancy. METHODS: We
      conducted a retrospective study in a large tertiary hospital in Israel. The study
      included 18 women with a diagnosis of cesarean scar pregnancy between 2000 and
      2009. RESULTS: The incidence of cesarean scar pregnancy among our parturient
      patients was 1 per 3000 for the general obstetric population and 1 per 531 among
      those with at least 1 cesarean delivery. Sixteen were treated primarily with
      methotrexate. Two were treated primarily by surgery, and 2 more were treated by
      surgery after failed methotrexate treatment. After cesarean scar pregnancy
      treatment, 7 women conceived spontaneously, and 1 conceived by in vitro
      fertilization-intracytoplasmic sperm injection. The remaining 10 (55%) did not
      wish to conceive again. Two of the women who became pregnant (25%) had recurrent
      cesarean scar pregnancy. CONCLUSIONS: This study shows encouraging results for
      fertility performance and obstetric outcomes after treatment of cesarean scar
      pregnancy. Nevertheless, the risk of recurrent cesarean scar pregnancy is not
      negligible.

PMID- 21876089
TI  - Reference ranges for the fetal cardiac circumference derived by cardio
      spatiotemporal image correlation from 14 to 40 weeks' gestation.
AB  - OBJECTIVES: The purpose of this study was to construct reference ranges for the
      fetal cardiac circumference derived from volume data sets obtained by cardio
      spatiotemporal image correlation. METHODS: A prospective descriptive study was
      conducted on normal singleton pregnancies with certain dates from 14 to 40 weeks'
      gestation. All underwent cardio-spatiotemporal image correlation to acquire
      volume data sets for subsequent analysis. Cardiac circumferences were measured
      offline in a multiplanar view with 4-dimensional imaging software. The reference
      ranges were constructed against gestational weeks and the biparietal diameter as
      independent variables, using regression models for both the mean and SD. RESULTS:
      A total of 678 satisfactory volumes were analyzed. Normal reference ranges for
      predicting means and SDs of the fetal cardiac circumference were established
      based on best-fitted equations. The mean cardiac circumference (millimeters) was
      modeled as a function of gestational age (weeks) and biparietal diameter
      (centimeters) as follows: cardiac circumference = -53.11 + 6.56 * gestational age
      - 0.035 * gestational age(2) (SD = 0.67 + 0.18 * gestational age) and -17.60 +
      17.68 * biparietal diameter (SD = 1.651 + 0.61 * biparietal diameter). Equations
      for z score calculation were also provided, and percentile charts for predicting
      the cardiac circumference at various points of gestational age and biparietal
      diameter were constructed. CONCLUSIONS: Normal reference ranges and z scores for
      the fetal cardiac circumference have been provided. These normative data may be
      useful tools for assessment of fetal cardiac size, especially in cardiomegaly due
      to fetal anemia.

PMID- 21876090
TI  - How the cervix shortens: an anatomic study using 3-dimensional transperineal
      sonography and image registration in singletons and twins.
AB  - OBJECTIVES: The purpose of this study was to use a fixed reference to study
      movement (displacement) of the cervical internal os from the second to the third
      trimester in singletons and twins. The rationale was to gain insight into
      anatomic changes associated with cervical shortening. METHODS: For each patient,
      2 transperineal scans were performed 12 weeks apart (20 and 32 weeks). The
      internal os and symphysis pubis were visualized in the same field of view. Image
      registration techniques were used to align the 2 scans using the symphysis as a
      fixed reference. Total displacement, anterior displacement, and inferior
      displacement of the internal os were measured. Displacements were correlated with
      cervical shortening. Bland-Altman plots and interobserver intraclass correlation
      coefficients were calculated. RESULTS: A total of 42 healthy participants were
      studied: 28 with singletons and 14 with twins. The mean +/- SD values for total
      displacement were 2.1 +/- 1.2 and 2.0 +/- 1.2 cm for singletons and twins,
      respectively (P = .75). The direction of displacement was significantly
      different. The mean anterior displacement was 1.1 cm greater for singletons than
      for twins (95% confidence interval, 0.29-2.0 cm, P = .01). Mean inferior
      displacement was 1.3 cm greater for twins than for singletons (95% confidence
      interval, 2.2-0.1 cm; P = .03). Only inferior displacement correlated with
      cervical shortening (P < .001; R(2) = 0.74). For every 2.2 cm of inferior
      displacement, the cervix shortened 1.0 cm. Assessments of reliability showed good
      agreement between 2 observers. CONCLUSIONS: The anatomic position of the internal
      cervical os depends on gestational age and fetal number. Cervical shortening
      correlated most strongly with inferior displacement.

PMID- 21876091
TI  - Sonographic diagnosis of ovarian torsion: accuracy and predictive factors.
AB  - OBJECTIVES: The purpose of this study was to determine the accuracy of
      sonographic diagnosis of ovarian torsion and the predictive value of typical
      sonographic signs. METHODS: The study included 63 women attending an ultrasound
      unit of a tertiary obstetrics and gynecology department in 2002 through 2008 who
      had suspected ovarian torsion on sonography and subsequently underwent
      laparoscopy. RESULTS: Sonography had diagnostic accuracy of 74.6% for ovarian
      torsion. Abnormal ovarian blood flow and the presence of free fluid were the most
      diagnostically accurate isolated sonographic signs (positive predictive values,
      80.0% and 89.2%, respectively; negative predictive values, 46.2% and 46.2%).
      Using combinations of sonographic signs yielded higher specificity and positive
      predictive values and lower sensitivity and negative predictive values for
      ovarian torsion. The diagnostic accuracy was largely affected by the ultrasound
      operator (mean +/- SD, 78.8% +/- 16.0%; range, 60.0%-100%). CONCLUSIONS: In the
      setting of a specialized ultrasound unit, sonographic diagnosis of ovarian
      torsion had high (74.6%) accuracy compared with previous reports. The absence of
      typical sonographic signs does not rule out ovarian torsion, especially when the
      clinical presentation is suggestive. Basing assessments on multiple sonographic
      signs, including Doppler evaluation, increases the diagnostic specificity.

PMID- 21876092
TI  - Recognition and application of the rectangular sonographic appearance of the
      urinary bladder.
AB  - OBJECTIVES: The purpose of this study was to investigate the rectangular
      sonographic appearance of the urinary bladder and its application. METHODS: A
      prospective study was conducted from May 2007 to December 2010. Fifty of 53
      healthy women and 31 female patients who had large pelvic fluid-filled cystic
      lesions but were otherwise healthy in workup were selected. The mean ages +/- SDs
      of the healthy participants and patients were 27.4 +/- 13.5 and 30.4 +/- 15.2
      years, respectively. Both the healthy participants and patients underwent
      abdominopelvic sonographic evaluations of the pelvic cavity, including the
      uterus, adnexa, and bladder. The appearance of the bladder was assessed when
      moderately filled, overfilled, and after voiding, and the volume, presence or
      absence of the rectangular appearance of the bladder, and presence or absence of
      large pelvic cystic lesions were observed and compared. RESULTS: The bladders of
      the 50 healthy participants and 31 patients with pelvic fluid-filled lesions
      could show the rectangular appearance, but all of the pelvic cystic lesions did
      not show this finding; the difference between the bladders and cystic lesions was
      significant (P < .001). The volumes between the moderately filled bladders of the
      patients (322.7 +/- 93.3 mL) and the cystic lesions (320.4 +/- 78.9 mL) showed no
      significant difference (P = .07), and neither did the volumes between the
      moderately filled bladders of the healthy participants (322.4 +/- 75.6 mL) and
      the cystic lesions (320.4 +/- 78.9 mL; P = .38). CONCLUSIONS: The bladder can
      show a rectangular appearance on sonography. The rectangular appearance is unique
      and can be used for identification of the bladder. Definitive recognition of the
      bladder is useful for avoiding errors in situations likely to be associated with
      bladder-related pitfalls.

PMID- 21876093
TI  - Establishing cutoff values for a quality assurance test using an ultrasound
      phantom in screening ultrasound examinations for hepatocellular carcinoma: an
      initial report of a nationwide survey in Korea.
AB  - OBJECTIVES: The purpose of this study was to evaluate the results of ultrasound
      (US) device testing using a US phantom and to determine cutoff values for phantom
      quality assurance tests in US examinations for the screening of hepatocellular
      carcinoma in Korea. METHODS: Ultrasound phantom images were acquired from the
      general hospitals in Korea that participated in the National Cancer Screening
      Program for hepatocellular carcinoma. Ultrasound images of the phantom were
      acquired with a 3.0- to 5.0-MHz convex transducer and evaluated in terms of the
      dead zone, vertical and horizontal measurement, axial and lateral resolution,
      sensitivity, and gray scale/dynamic range. Appropriate cutoff values were
      determined to guarantee minimal qualifications for the performance of the US
      scanners. RESULTS: Three hundred fifty-seven US scanners were tested using the
      following cutoff values: less than 2 mm for the dead zone, 5% discrepancy in the
      vertical measurement, 7.5% discrepancy in the horizontal measurement, all 11
      identifiable line targets for axial and lateral resolution, more than 14 cm for
      sensitivity, and more than 4 cylindrical structures for gray scale/dynamic range.
      With these criteria, 283 US scanners (79.3%) passed the tests. The most common
      cause of disqualification was the dynamic range/gray scale. No statistical
      difference was observed in the disqualification rate between 3 groups based on
      different years of manufacture. CONCLUSIONS: Through this study, we have defined
      cutoff values for phantom images acquired with US scanners. These will be used in
      performing screening US examinations for hepatocellular carcinoma in Korea.

PMID- 21876094
TI  - Sonographic appearance of the posterior interosseous nerve at the wrist.
AB  - OBJECTIVES: The purpose of this study was to determine whether sonography can
      identify the distal posterior interosseous nerve at the wrist. METHODS: On the
      basis of previous anatomic descriptions, high-resolution musculoskeletal
      sonography was used in an attempt to identify the distal posterior interosseous
      nerve in the wrists of 20 unembalmed cadaveric specimens (11 male and 9 female;
      ages 54-98 years). High-frequency scanning (17-5 MHz) of the fourth dorsal
      extensor compartment revealed a small (1-3 mm) hypoechoic structure located on
      the compartment floor, presumed to represent the posterior interosseous nerve.
      Electronic calipers measured the distance between Lister's tubercle and this
      structure, as well as the structure's radial-ulnar width and volar-dorsal height.
      The presumed posterior interosseous nerves of 10 specimens were then injected
      with diluted colored latex using sonographic guidance. Subsequent dissection
      definitively identified the sonographically visualized and injected structure.
      RESULTS: Dissection revealed latex within the posterior interosseous nerve in all
      10 injected specimens, thus confirming that the sonographically visualized
      structure represented the distal posterior interosseous nerve. The nerve was
      identified sonographically in all 20 examined specimens, was located an average
      of 4.88 mm (range, 2.10-10.0 mm) ulnar to Lister's tubercle, and had an average
      width and height of 2.35 mm (range, 1.20-3.50 mm) and 1.01 mm (range, 0.80-1.40
      mm), respectively. CONCLUSIONS: High-resolution sonography can reliably identify
      the distal posterior interosseous nerve within the fourth dorsal extensor
      compartment. Clinicians should consider formal evaluation of the posterior
      interosseous nerve in patients presenting with dorsal wrist pain syndromes.
      Future investigations should explore the potential role of sonographically guided
      percutaneous procedures directed at the posterior interosseous nerve.

PMID- 21876095
TI  - Effect of SonoVue on the synovial membrane in rabbit knees.
AB  - OBJECTIVES: The purpose of this study was to evaluate the effect of intra
      articular injection of SonoVue (sulfur hexafluoride with a phospholipid shell;
      Bracco SpA, Milan, Italy) on the synovial membrane in an animal model. METHODS:
      Twenty-one New Zealand White rabbits (42 knees) were used in this study. We
      injected the knees with normal saline (saline group; n = 21) and SonoVue (SonoVue
      group; n = 21). A histologic examination of the knees was performed out at 3 and
      12 hours and 3, 7, 15, 30, and 45 days after injection. Four histologic
      parameters (synovial hyperplasia, synovial stroma, vascular dilatation, and
      inflammatory infiltrates) were graded separately. RESULTS: We found no
      significant differences in this study for synovial hyperplasia, vascular
      dilatation, or inflammatory infiltrates between the saline and SonoVue groups. A
      significant difference was only observed for synovial stroma (P < .05), and most
      of the histologic changes were mild in the saline group and moderate in the
      SonoVue group. The histologic changes observed in this study are considered
      transitory and reversible. CONCLUSIONS: The results suggest that intra-articular
      injection of SonoVue is a safe procedure.

PMID- 21876096
TI  - Ultrasound- and liposome microbubble-mediated targeted gene transfer to
      cardiomyocytes in vivo accompanied by polyethylenimine.
AB  - OBJECTIVES: Gene transfer to cardiomyocytes in vivo has received much research
      attention in the last decade but remains a substantial hurdle. Gene transfer
      using ultrasound-targeted microbubble destruction is a promising tool for gene
      therapy. Little data have shown the feasibility and optimization of this method
      for primary myocardial disease. In this study, we sought to determine the
      feasibility and efficiency of in vivo gene transfer to the myocardium mediated by
      ultrasound-targeted microbubble destruction accompanied by polyethylenimine.
      METHODS: Three plasmids (luciferase reporter, red fluorescent protein reporter,
      and enhanced green fluorescent protein reporter) were used in this study. The
      ultrasound parameters were also optimized. A solution containing phosphate
      buffered saline, a plasmid, plasmid complex, or polyethylenimine/plasmid, and
      liposome microbubbles was injected via a tail vein with (study) or without
      (control) transthoracic ultrasound irradiation. The efficiency of reporter gene
      transfer was determined by detection of luciferase activity or microscopy, and
      histologic investigations of the tissue specimens were performed. RESULTS:
      Ultrasound-targeted microbubble destruction significantly increased luciferase
      activity in vivo compared to plasmids and microbubbles alone (P < .001). More
      importantly, the increase in transgene expression was significantly related to
      ultrasound-targeted microbubble destruction in the presence of polyethylenimine
      (P < .001). In addition, fluorescein expression was present in all sections that
      received ultrasound-targeted microbubble destruction. The fluorescent reporter
      genes and luciferase plasmid all had similar results. Regardless of ultrasound
      exposure, expression in other organs was close to a background level except for
      the liver and lung. Hematoxylin-eosin staining showed no notable myocardial
      injury or death in control and treated mice. CONCLUSIONS: An atraumatic targeted
      gene delivery technique based on ultrasound-targeted microbubble destruction and
      polyethylenimine has been developed to transfect cardiomyocytes in vivo. If a
      suitable target gene is added, the novel technique could be highly effective in
      many kinds of heart disease.

PMID- 21876097
TI  - Quantitative measurement for thyroid cancer characterization based on
      elastography.
AB  - OBJECTIVES: The purpose of this study was to evaluate color thyroid elastograms
      quantitatively and objectively and select more effective features to
      differentiate benign from malignant thyroid nodules. METHODS: The study was
      approved by the Ethics Committee of Harbin Medical University. A total of 125
      cases (56 malignant and 69 benign) were analyzed in this retrospective study. The
      original color thyroid elastograms were transferred from the red-green-blue color
      space to the hue-saturation-value color space. The elasticity information was
      represented by the hue component of color elastograms. The lesion regions were
      delineated by radiologists, and statistical and textural features were extracted.
      Then the most effective and reliable features among them were selected by using a
      minimum redundancy-maximum relevance algorithm. The selected features were input
      to a support vector machine to differentiate benign from malignant thyroid
      nodules. RESULTS: The classification accuracy was 93.6% when the hard area ratio
      and textural feature (energy) of the lesion region were used. The area under the
      receiver operating characteristic curve for the hard area ratio was higher than
      that for the strain ratio (0.97 versus 0.87; P < .01), and the area under the
      curve for the hard area ratio was also higher than that for the color score (0.97
      versus 0.80; P < .001). The results also showed that the features were robust for
      lesion region delineation. CONCLUSIONS: The hard area ratio is an important and
      quantitative metric for elastograms. Quantitative analysis of elastograms using
      computer-aided diagnostic techniques can improve diagnostic accuracy.

PMID- 21876098
TI  - Clinical value of integrated [18F]fluoro-2-deoxy-D-glucose positron emission
      tomography/computed tomography in the preoperative assessment of papillary
      thyroid carcinoma: comparison with sonography.
AB  - OBJECTIVES: The purpose of this study was to evaluate the clinical value of
      preoperative [(18)F]fluoro-2-deoxy-D-glucose (FDG) positron emission
      tomography/computed tomography (PET/CT) by comparing it to neck sonography in
      papillary thyroid carcinoma. METHODS: The diagnostic accuracies of PET/CT and
      sonography for detecting cervical node metastasis were compared. The association
      between FDG uptake in the primary tumor and the prognostic factors of
      differentiated thyroid cancer, such as tumor size, multiplicity, extrathyroid
      extension, and lymph node metastasis, was also assessed. RESULTS: Positron
      emission tomography/computed tomography showed lower sensitivity and higher
      specificity than sonography for detection of cervical node metastasis; however,
      no statistically significant difference was noted (P > .99). Only the tumor size
      was associated with FDG uptake in the primary tumor. CONCLUSIONS: [(18)F]Fluoro-2
      deoxy-d-glucose PET/CT could not provide additional information compared to neck
      sonography.

PMID- 21876099
TI  - Meeting abstracts to published manuscripts: how does emergency ultrasound
      compare?
AB  - OBJECTIVES: Very little is known about publication rates of emergency ultrasound
      abstracts as peer-reviewed manuscripts in the years after their presentation at
      national meetings. The objectives of this study were to determine trends in
      publication patterns of emergency ultrasound abstracts presented at Society for
      Academic Emergency Medicine and American College of Emergency Physicians annual
      national meetings as full indexed articles in peer-reviewed journals and compare
      emergency ultrasound with emergency medical services (EMS) and toxicology
      subspecialties. METHODS: A cross-sectional study was conducted at an academic
      medical center. All emergency ultrasound, EMS, and toxicology abstracts presented
      at both national meetings from 1999 to 2008 were entered into a database. An
      online PubMed/MEDLINE search was performed for full-length peer-reviewed
      manuscript publications corresponding to these abstracts. The proportion of
      abstracts presented, manuscript publication rate, time to publication, type of
      journal (emergency medicine versus non-emergency medicine), and journal impact
      factor were compared across the 3 subspecialties. RESULTS: Over the 10-year
      period, 452 emergency ultrasound, 651 EMS, and 376 toxicology abstracts were
      presented at both meetings. The proportion of abstracts presented from 1999 to
      2008 increased significantly for emergency ultrasound (1.7% versus 6.5%) compared
      with toxicology (3.5% versus 4.9%) and EMS (8.1% versus 5.8%; P < .01). There
      were no significant differences in manuscript publication rates between emergency
      ultrasound (22.8%), EMS (23.4%), and toxicology (20.7%). No significant
      differences were found in the time to publication (P = .53) and journal type (P =
      .2) between the 3 subspecialties. CONCLUSIONS: The emergency ultrasound
      manuscript publication rate and mean time to publication compare favorably with
      EMS and toxicology subspecialties.

PMID- 21876100
TI  - Sonography of the spleen.
AB  - This pictorial essay will review and discuss the aspects of differential
      diagnosis with splenic sonography, including recent literature and exemplary
      pictorial sonographic cases. Although the spleen is well evaluated by computed
      tomography and magnetic resonance imaging, sonography has certain advantages,
      including its ubiquitous availability, lack of ionizing radiation, and low cost.
      Sonography of the spleen plays an important role in emergency diagnosis of
      splenic rupture and hemorrhage. The additional use of contrast-enhanced
      sonography can improve the diagnostic validity. Depending on the indication,
      sonography of the spleen is especially important for oncologic differential
      diagnosis of focal lesions, follow-up examinations, and image guidance of
      therapeutic interventions.

PMID- 21876101
TI  - Granular cell tumor of the male breast: two case descriptions and brief review of
      the literature.
AB  - A granular cell tumor of breast is a rare and usually benign tumor originating
      from Schwann cells. The mammographic and sonographic appearances of a granular
      cell tumor pose a diagnostic dilemma because of its similarity to breast
      malignancy. We describe 2 cases of breast granular cell tumors in male patients,
      which were confirmed after surgical excision and histologic examination.

PMID- 21876102
TI  - Breast abscess after nipple piercing: sonographic findings with clinical
      correlation.
AB  - The purpose of this series was to review the spectrum of clinical and sonographic
      features associated with infection after nipple piercing. Between 2002 and 2010,
      6 patients presented to our breast center with a breast abscess after nipple
      piercing. A retrospective analysis of the imaging findings was performed with
      clinical and pathologic correlation. Patients with breast infections after nipple
      piercing tend to be young, and the timing since piercing varies from 2 weeks to
      17 months. Sonography showed a complex or hypoechoic mass in 5 of 6 patients.
      Treatment of breast abscesses included surgical incision and drainage,
      percutaneous drainage, and antibiotic therapy. Surgical evacuation is commonly
      performed; however, sonographically guided aspiration may be an appropriate
      management strategy.

PMID- 21876103
TI  - Thyroid hemiagenesis: a rare finding.

PMID- 21876104
TI  - Fetal gallbladder duplication.

PMID- 21876105
TI  - Fetal rhabdomyosarcoma of the right lower extremity.

PMID- 21876106
TI  - Models and mechanisms of regenerative biology across phylogeny: introduction to a
      virtual symposium in The Biological Bulletin.

PMID- 21876109
TI  - Spontaneous regeneration of the central nervous system in gastropods.
AB  - Of all organs in mammals including humans, the brain has the most limited
      regenerative capacity after injury or damage. In spite of extensive efforts to
      treat ischemic/stroke injury of the brain, thus far no reliable therapeutic
      method has been developed. However, some molluscan species show remarkable brain
      regenerative ability and can achieve full functional recovery following injury.
      The terrestrial pulmonates are equipped with a highly developed olfactory center,
      called the procerebrum, which is involved in olfactory discrimination and odor
      aversion learning. Recent studies revealed that the procerebrum of the land slug
      can spontaneously recover structurally and functionally relatively soon after
      injury. Surprisingly, no exogenous interventions are required for this
      reconstitutive repair. The neurogenesis continues in the procerebrum in adult
      slugs as in the hippocampus and the olfactory bulb of mammals, and the
      reconstitutive regeneration seems to be mediated by enhanced neurogenesis. In
      this review, we discuss the relationship between neurogenesis and the
      regenerative ability of the brain, and also the evolutionary origin of the brain
      structures in which adult neurogenesis has been observed.

PMID- 21876110
TI  - Asexual propagation and regeneration in colonial ascidians.
AB  - Regeneration is widely distributed among the metazoans. However, clear
      differences exist as to the degree of regenerative capacity: some phyla can only
      replace missing body parts, whereas others can generate entirely new individuals.
      Ascidians are animals that possess a remarkable regenerative plasticity and
      exhibit a great diversity of mechanisms for asexual propagation and survival.
      They are marine invertebrate members of the subphylum Tunicata and represent
      modern-day descendants of the chordate ancestor; in their tadpole stage they
      exhibit a chordate body plan that is resorbed during metamorphosis. Solitary
      species grow into an adult that can reach several centimeters in length, whereas
      colonial species grow by asexual propagation, creating a colony of genetically
      identical individuals. In this review, we present an overview of the biology of
      colonial ascidians as a paradigm for study in stem cell and regenerative biology.
      Focusing on botryllid ascidians, we introduce the potential roles played by
      multipotent epithelia and multipotent/pluripotent stem cells as source of asexual
      propagation and regenerative plasticity in the different budding mechanisms, and
      consider the putative mechanism of body repatterning in a non-embryonic scenario.
      We also discuss the involvement of intra-colony homeostatic processes in
      regulating budding potential, and the functional link between allorecognition,
      chimerism, and regenerative potential.

PMID- 21876108
TI  - Regeneration in the era of functional genomics and gene network analysis.
AB  - What gives an organism the ability to regrow tissues and to recover function
      where another organism fails is the central problem of regenerative biology. The
      challenge is to describe the mechanisms of regeneration at the molecular level,
      delivering detailed insights into the many components that are cross-regulated.
      In other words, a broad, yet deep dissection of the system-wide network of
      molecular interactions is needed. Functional genomics has been used to elucidate
      gene regulatory networks (GRNs) in developing tissues, which, like regeneration,
      are complex systems. Therefore, we reason that the GRN approach, aided by next
      generation technologies, can also be applied to study the molecular mechanisms
      underlying the complex functions of regeneration. We ask what characteristics a
      model system must have to support a GRN analysis. Our discussion focuses on
      regeneration in the central nervous system, where loss of function has
      particularly devastating consequences for an organism. We examine a cohort of
      cells conserved across all vertebrates, the reticulospinal (RS) neurons, which
      lend themselves well to experimental manipulations. In the lamprey, a jawless
      vertebrate, there are giant RS neurons whose large size and ability to regenerate
      make them particularly suited for a GRN analysis. Adding to their value, a
      distinct subset of lamprey RS neurons reproducibly fail to regenerate, presenting
      an opportunity for side-by-side comparison of gene networks that promote or
      inhibit regeneration. Thus, determining the GRN for regeneration in RS neurons
      will provide a mechanistic understanding of the fundamental cues that lead to
      success or failure to regenerate.

PMID- 21876111
TI  - Mature and juvenile tissue models of regeneration in small fish species.
AB  - The multitude of cells constituting organisms are fragile and easily damaged day
      by day. Therefore, maintenance of tissue morphology and function is fundamental
      for multicellular organisms to attain long life. For proper maintenance of tissue
      integrity, organisms must have mechanisms that detect the loss of tissue mass,
      activate the de novo production of cells, and organize those cells into
      functional tissues. However, these processes are only poorly understood. Here we
      give an overview of adult and juvenile tissue regeneration models in small fish
      species, such as zebrafish and medaka, and highlight recent advances at the
      molecular level. From these advances, we have come to realize that the epidermal
      and mesenchymal parts of the regenerating fish fin-that is, the wound epidermis
      and blastema, respectively-comprise heterogeneous populations of cells with
      different molecular identities that can be termed "compartments." These
      compartments and their mutual interactions are thought to play important roles in
      promoting the proper progression of tissue regeneration. We further describe the
      current understanding of these compartments and discuss the possible approaches
      to affording a better understanding of their roles and interactions during
      regeneration.

PMID- 21876112
TI  - Extracellular electrical fields direct wound healing and regeneration.
AB  - Endogenous DC electric fields (EFs) are important, fundamental components of
      development, regeneration, and wound healing. The fields are the result of
      polarized ion transport and current flow through electrically conductive
      pathways. Nullification of endogenous EFs with pharmacological agents or applied
      EFs of opposite polarity disturbs the aforementioned processes, while enhancement
      increases the rate of wound closure and the extent of regeneration. EFs are
      applied to humans in the clinic, to provide an overwhelming signal for the
      enhancement of healing of chronic wounds. Although clinical trials, spanning a
      course of decades, have shown that applied EFs enhance healing of chronic wounds,
      the mechanisms by which cells sense and respond to these weak cues remains
      unknown. EFs are thought to influence many different processes in vivo. However,
      under more rigorously controlled conditions in vitro, applied EFs induce cellular
      polarity and direct migration and outgrowth. Here we review the generation of
      endogenous EFs, the results of their alteration, and the mechanisms by which
      cells may sense these weak fields. Understanding the mechanisms by which native
      and applied EFs direct development and repair will enable current and future
      therapeutic applications to be optimized.

PMID- 21876113
TI  - Gut regeneration in holothurians: a snapshot of recent developments.
AB  - Visceral regeneration in sea cucumbers has been studied since early last century;
      however, it is only within the last 15 years that real progress has been made in
      understanding the cellular and molecular events involved. In the present review,
      we bring together these recent studies, providing readers with basic information
      on the anatomy and histology of the normal gut and detailing the changes in
      tissue organization and gene expression that occur during the regenerative
      process. We discuss the nature and possible sources of cells involved in the
      formation of the intestinal regenerate as well as the role of cell death and
      proliferation in this process. In addition, we compare gut formation during
      regeneration and during embryogenesis. Finally, we describe the molecular studies
      that have helped advance regenerative studies in holothurians and integrate the
      gene expression information with data on cellular events. Studies on visceral
      regeneration in these echinoderms provide a unique view that complements
      regeneration studies in other animal phyla, which are mainly focused on whole
      animal regeneration or appendage regeneration.

PMID- 21876115
TI  - Pattern of cell proliferation during budding in the colonial ascidian Diplosoma
      listerianum.
AB  - Many invertebrates reproduce asexually by budding, but morphogenesis and the role
      of cell proliferation in this diverse and nonconserved regeneration-like process
      are generally poorly understood and particularly little investigated in didemnid
      ascidians. We here analyzed cell proliferation patterns and telomerase activity
      during budding in the colonial didemnid ascidian Diplosoma listerianum, with
      special focus on the thoracic bud where a new brain develops de novo. To help
      define developmental stages of the thoracic bud, the distribution of acetylated
      tubulin was also examined. We found extensive cell proliferation in both the
      thoracic and abdominal buds of D. listerianum as well as higher telomerase
      activity in bud tissue compared to adult tissues. In the parent adult,
      proliferation was found in various tissues, but was especially intense in the
      adult esophagus and epicardial structures that protrude into the proliferating
      and developing buds, confirming these tissues as the primary source of the cells
      that form the buds. The neural complex in the thoracic bud forms from a hollow
      tube that appears to separate into the neural gland and the cerebral ganglion.
      Whereas most of the bud undergoes proliferation, including the hollow tube and
      the neural gland, the cerebral ganglion shows little or no proliferation. Pulse
      chase labeling experiments indicate that the ganglion, as well as the myocardium,
      in adult zooids are instead composed of postmitotic cells.

PMID- 21876114
TI  - Regulation and restoration of motoneuronal synaptic transmission during
      neuromuscular regeneration in the pulmonate snail Helisoma trivolvis.
AB  - Regeneration of motor systems involves reestablishment of central control
      networks, reinnervation of muscle targets by motoneurons, and reconnection of
      neuromodulatory circuits. Still, how these processes are integrated as motor
      function is restored during regeneration remains ill defined. Here, we examined
      the mechanisms underlying motoneuronal regeneration of neuromuscular synapses
      related to feeding movements in the pulmonate snail Helisoma trivolvis. Neurons
      B19 and B110, although activated during different phases of the feeding pattern,
      innervate similar sets of muscles. However, the percentage of muscle fibers
      innervated, the efficacy of excitatory junction potentials, and the strength of
      muscle contractions were different for each cell's specific connections. After
      peripheral nerve crush, a sequence of transient electrical and chemical
      connections formed centrally within the buccal ganglia. Neuromuscular synapse
      regeneration involved a three-phase process: the emergence of spontaneous
      synaptic transmission (P1), the acquisition of evoked potentials of weak efficacy
      (P2), and the establishment of functional reinnervation (P3). Differential
      synaptic efficacy at muscle contacts was recapitulated in cell culture.
      Differences in motoneuronal presynaptic properties (i.e., quantal content) were
      the basis of disparate neuromuscular synapse function, suggesting a role for
      retrograde target influences. We propose a homeostatic model of molluscan motor
      system regeneration. This model has three restoration events: (1) transient
      central synaptogenesis during axonal outgrowth, (2) intermotoneuronal inhibitory
      synaptogenesis during initial neuromuscular synapse formation, and (3) target
      dependent regulation of neuromuscular junction formation.

PMID- 21876116
TI  - FGF signaling is required for lens regeneration in Xenopus laevis.
AB  - In species of the frog genus Xenopus, lens regeneration occurs through a process
      of transdifferentiation, in which cornea epithelial cells presumably undergo
      dedifferentiation and subsequently redifferentiate to form a new lens.
      Experimental studies have shown that the retina provides the key signal required
      to trigger this process once the original lens is removed. A previous study
      showed that addition of an exogenous fibroblast growth factor (i.e., FGF1
      protein) could initiate transdifferentiation of cornea epithelial cells in
      culture. To determine the role of FGF signaling in X. laevis lens regeneration,
      we have examined the presence of specific FGFs and their receptors (FGFRs) during
      this process and evaluated the necessity of FGFR signaling. Reverse transcriptase
      polymerase chain reaction analyses reveal that a number of FGF family members are
      expressed in cornea epithelium and retinal tissues both before and during the
      process of lens regeneration. Of these, FGF1, FGF8, and FGF9 are expressed
      principally in retinal tissue and not in the cornea epithelium. Hence, these
      ligands could represent key signaling factors originating from the retina that
      trigger regeneration. The results of experiments using an in vitro eye culture
      system and an FGFR inhibitor (SU5402) suggest that FGFR signaling is required for
      lens regeneration in Xenopus.

PMID- 21876117
TI  - Chuvash polycythemia VHLR200W mutation is associated with down-regulation of
      hepcidin expression.
AB  - Hypoxia is known to reduce the expression of hepcidin, the master regulator of
      iron metabolism. However, it is not clear whether this response is primarily
      related to increased erythropoiesis driven by hypoxically stimulated
      erythropoietin or to a more direct effect of hypoxia on hepcidin expression. The
      germline loss-of-function VHL(R200W) mutation is common in Chuvashia, Russia, and
      also occurs elsewhere. VHL(R200W) homozygotes have elevated hypoxia-inducible
      factor 1alpha (HIF-1alpha) and HIF-2alpha levels, increased red cell mass,
      propensity to thrombosis, and early mortality. Ninety VHL(R200W) homozygotes and
      52 controls with normal VHL alleles from Chuvashia, Russia, were studied under
      basal circumstances. In univariate analyses, serum hepcidin concentration was
      correlated positively with serum ferritin concentration and negatively with
      homozygosity for VHL(R200W). After adjustment for serum erythropoietin and
      ferritin concentrations by multiple linear regression, the geometric mean (95%
      confidence interval of mean) hepcidin concentration was 8.1 (6.3-10.5) ng/mL in
      VHL(R200W) homozygotes versus 26.9 (18.6-38.0) ng/mL in controls (P < .001). In
      contrast, a significant independent relationship of serum erythropoietin,
      hemoglobin, or RBC count with hepcidin was not observed. In conclusion, up
      regulation of the hypoxic response leads to decreased expression of hepcidin that
      may be independent of increased erythropoietin levels and increased RBC counts.

PMID- 21876118
TI  - General population low-count CLL-like MBL persists over time without clinical
      progression, although carrying the same cytogenetic abnormalities of CLL.
AB  - Monoclonal B-cell lymphocytosis (MBL) is classified as chronic lymphocytic
      leukemia (CLL)-like, atypical CLL, and CD5(-) MBL. The number of B cells per
      microliter divides CLL-like MBL into MBL associated with lymphocytosis (usually
      detected in a clinical setting) and low-count MBL detected in the general
      population (usually identified during population screening). After a median
      follow-up of 34 months we reevaluated 76 low-count MBLs with 5-color flow
      cytometry: 90% of CLL-like MBL but only 44.4% atypical CLL and 66.7% CD5(-) MBL
      persisted over time. Population-screening CLL-like MBL had no relevant cell count
      change, and none developed an overt leukemia. In 50% of the cases FISH showed CLL
      related chromosomal abnormalities, including monoallelic or biallelic 13q
      deletions (43.8%), trisomy 12 (1 case), and 17p deletions (2 cases). The analysis
      of the T-cell receptor beta (TRBV) chains repertoire showed the presence of
      monoclonal T-cell clones, especially among CD4(high)CD8(low), CD8(high)CD4(low) T
      cells. TRBV2 and TRBV8 were the most frequently expressed genes. This study
      indicates that (1) the risk of progression into CLL for low-count population
      screening CLL-like MBL is exceedingly rare and definitely lower than that of
      clinical MBL and (2) chromosomal abnormalities occur early in the natural history
      and are possibly associated with the appearance of the typical phenotype.

PMID- 21876119
TI  - Pharmacokinetics, pharmacodynamics, and pharmacogenetics of hydroxyurea treatment
      for children with sickle cell anemia.
AB  - Hydroxyurea therapy has proven laboratory and clinical efficacies for children
      with sickle cell anemia (SCA). When administered at maximum tolerated dose (MTD),
      hydroxyurea increases fetal hemoglobin (HbF) to levels ranging from 10% to 40%.
      However, interpatient variability of percentage of HbF (%HbF) response is high,
      MTD itself is variable, and accurate predictors of hydroxyurea responses do not
      currently exist. HUSTLE (NCT00305175) was designed to provide first-dose
      pharmacokinetics (PK) data for children with SCA initiating hydroxyurea therapy,
      to investigate pharmacodynamics (PD) parameters, including HbF response and MTD
      after standardized dose escalation, and to evaluate pharmacogenetics influences
      on PK and PD parameters. For 87 children with first-dose PK studies, substantial
      interpatient variability was observed, plus a novel oral absorption phenotype
      (rapid or slow) that influenced serum hydroxyurea levels and total hydroxyurea
      exposure. PD responses in 174 subjects were robust and similar to previous
      cohorts; %HbF at MTD was best predicted by 5 variables, including baseline %HbF,
      whereas MTD was best predicted by 5 variables, including serum creatinine.
      Pharmacogenetics analysis showed single nucleotide polymorphisms influencing
      baseline %HbF, including 5 within BCL11A, but none influencing MTD %HbF or dose.
      Accurate prediction of hydroxyurea treatment responses for SCA remains a worthy
      but elusive goal.

PMID- 21876120
TI  - Immunologic effects of rituximab on the human spleen in immune thrombocytopenia.
AB  - Immune thrombocytopenia (ITP) is an autoimmune disease with a complex
      pathogenesis. As in many B cell-related autoimmune diseases, rituximab (RTX) has
      been shown to increase platelet counts in some ITP patients. From an immunologic
      standpoint, the mode of action of RTX and the reasons underlying its limited
      efficacy have yet to be elucidated. Because splenectomy is a cornerstone
      treatment of ITP, the immune effect of RTX on this major secondary lymphoid organ
      was investigated in 18 spleens removed from ITP patients who were treated or not
      with RTX. Spleens from ITP individuals had follicular hyperplasia consistent with
      secondary follicles. RTX therapy resulted in complete B-cell depletion in the
      blood and a significant reduction in splenic B cells, but these patients did not
      achieve remission. Moreover, whereas the percentage of circulating regulatory T
      cells (Tregs) was similar to that in controls, splenic Tregs were reduced in ITP
      patients. Interestingly, the ratio of proinflammatory Th1 cells to suppressive
      Tregs was increased in the spleens of patients who failed RTX therapy. These
      results indicate that although B cells are involved in ITP pathogenesis, RTX
      induced total B-cell depletion is not correlated with its therapeutic effects,
      which suggests additional immune-mediated mechanisms of action of this drug.

PMID- 21876122
TI  - Blood consult: high Sokal risk chronic myeloid leukemia and suboptimal response.

PMID- 21876121
TI  - Fine-tuning nucleophosmin in macrophage differentiation and activation.
AB  - M-CSF-driven differentiation of peripheral blood monocytes is one of the sources
      of tissue macrophages. In humans and mice, the differentiation process involves
      the activation of caspases that cleave a limited number of proteins. One of these
      proteins is nucleophosmin (NPM1), a multifunctional and ubiquitous protein. Here,
      we show that caspases activated in monocytes exposed to M-CSF cleave NPM1 at D213
      to generate a 30-kDa N-terminal fragment. The protein is further cleaved into a
      20-kDa fragment, which involves cathepsin B. NPM1 fragments contribute to the
      limited motility, migration, and phagocytosis capabilities of resting
      macrophages. Their activation with lipopolysaccharides inhibits proteolytic
      processes and restores expression of the full-length protein that negatively
      regulates the transcription of genes encoding inflammatory cytokines (eg, NPM1 is
      recruited with NF-kappaB on the MCP1 gene promoter to decrease its
      transcription). In mice with heterozygous npm gene deletion, cytokine production
      in response to lipopolysaccharides, including CXCL1 (KC), MCP1, and MIP2, is
      dramatically enhanced. These results indicate a dual function of NPM1 in M-CSF
      differentiated macrophages. Proteolysis of the protein participates in the
      establishment of a mature macrophage phenotype. In response to inflammatory
      stimuli, the full-length protein negatively regulates inflammatory cytokine
      production.

PMID- 21876124
TI  - Quantitative lipid composition of cell envelopes of Corynebacterium glutamicum
      elucidated through reverse micelle extraction.
AB  - Cells of the Corynebacterium-Nocardia-Mycobacterium group of bacteria are
      surrounded by an outer membrane (OM) containing mycolic acids that are covalently
      linked to the underlying arabinogalactan-peptidoglycan complex. This OM
      presumably acts as a permeability barrier that imparts high levels of intrinsic
      drug resistance to some members of this group, such as Mycobacterium
      tuberculosis, and its component lipids have been studied intensively in a
      qualitative manner over the years. However, the quantitative lipid composition of
      this membrane has remained obscure, mainly because of difficulties in isolating
      it without contamination from the inner cytoplasmic membrane. Here we use the
      extraction, with reverse surfactant micelles, of intact cells of Corynebacterium
      glutamicum and show that this method extracts the free OM lipids quantitatively
      with no contamination from lipids of the cytoplasmic membrane, such as
      phosphatidylglycerol. Although only small amounts of corynomycolate were
      esterified to arabinogalactan, a large amount of cardiolipin was present in a
      nonextractable form, tightly associated, possibly covalently, with the
      peptidoglycan-arabinogalactan complex. Furthermore, we show that the OM contains
      just enough lipid hydrocarbons to produce a bilayer covering the cell surface,
      with its inner leaflet composed mainly of the aforementioned nonextractable
      cardiolipin and its outer leaflet composed of trehalose dimycolates,
      phosphatidylinositol mannosides, and highly apolar lipids, similar to the
      Minnikin model of 1982. The reverse micelle extraction method is also useful for
      extracting proteins associated with the OM, such as porins.

PMID- 21876123
TI  - Beta1 integrin cytoplasmic tyrosines promote skin tumorigenesis independent of
      their phosphorylation.
AB  - beta1 integrin tyrosine phosphorylation by oncogenic kinases, such as Src, has
      been predicted to induce tumorigenesis by disrupting adhesion and modifying
      integrin signaling. We directly tested this hypothesis by subjecting mice with
      "nonphosphorylatable" tyrosine-to-phenylalanine substitutions in the conserved
      beta1 cytoplasmic tail NPxY motifs to a model of cutaneous carcinogenesis in the
      presence or absence of elevated Src activity. We found that hydrophobic
      phenylalanine substitutions of both tyrosines diminished the binding of tail
      interacting proteins, including talins and kindlins, resulting in reduced beta1
      mediated adhesion, focal adhesion kinase (FAK) signaling, and epidermal
      progenitor cell-derived skin tumors. However, increased Src activity drove tumor
      formation independent of the phenylalanine substitutions by enhancing FAK
      activity, which in turn maintained the epidermal progenitor state and blocked
      keratinocyte differentiation. We conclude that a Src/FAK signaling unit inhibits
      differentiation to promote tumorigenesis downstream of beta1 integrin and
      independent of beta1 integrin tyrosine phosphorylation.

PMID- 21876125
TI  - A widespread class of reverse transcriptase-related cellular genes.
AB  - Reverse transcriptases (RTs) polymerize DNA on RNA templates. They fall into
      several structurally related but distinct classes and form an assemblage of RT
      like enzymes that, in addition to RTs, also includes certain viral RNA-dependent
      RNA polymerases (RdRP) synthesizing RNA on RNA templates. It is generally
      believed that most RT-like enzymes originate from retrotransposons or viruses and
      have no specific function in the host cell, with telomerases being the only
      notable exception. Here we report on the discovery and properties of a unique
      class of RT-related cellular genes collectively named rvt. We present evidence
      that rvts are not components of retrotransposons or viruses, but single-copy
      genes with a characteristic domain structure that may contain introns in
      evolutionarily conserved positions, occur in syntenic regions, and evolve under
      purifying selection. These genes can be found in all major taxonomic groups
      including protists, fungi, animals, plants, and even bacteria, although they
      exhibit patchy phylogenetic distribution in each kingdom. We also show that the
      RVT protein purified from one of its natural hosts, Neurospora crassa, exists in
      a multimeric form and has the ability to polymerize NTPs as well as dNTPs in
      vitro, with a strong preference for NTPs, using Mn(2+) as a cofactor. The
      existence of a previously unknown class of single-copy RT-related genes calls for
      reevaluation of the current views on evolution and functional roles of RNA
      dependent polymerases in living cells.

PMID- 21876126
TI  - Asymmetric dispersal allows an upstream region to control population structure
      throughout a species' range.
AB  - In a single well-mixed population, equally abundant neutral alleles are equally
      likely to persist. However, in spatially complex populations structured by an
      asymmetric dispersal mechanism, such as a coastal population where larvae are
      predominantly moved downstream by currents, the eventual frequency of neutral
      haplotypes will depend on their initial spatial location. In our study of the
      progression of two spatially separate, genetically distinct introductions of the
      European green crab (Carcinus maenas) along the coast of eastern North America,
      we captured this process in action. We documented the shift of the genetic cline
      in this species over 8 y, and here we detail how the upstream haplotypes are
      beginning to dominate the system. This quantification of an evolving genetic
      boundary in a coastal system demonstrates that novel genetic alleles or
      haplotypes that arise or are introduced into upstream retention zones (regions
      whose export of larvae is not balanced by import from elsewhere) will increase in
      frequency in the entire system. This phenomenon should be widespread when there
      is asymmetrical dispersal, in the oceans or on land, suggesting that the upstream
      edge of a species' range can influence genetic diversity throughout its
      distribution. Efforts to protect the upstream edge of an asymmetrically
      dispersing species' range are vital to conserving genetic diversity in the
      species.

PMID- 21876127
TI  - Inflammasome is a central player in the induction of obesity and insulin
      resistance.
AB  - Inflammation plays a key role in the pathogenesis of obesity. Chronic overfeeding
      leads to macrophage infiltration in the adipose tissue, resulting in
      proinflammatory cytokine production. Both microbial and endogenous danger signals
      trigger assembly of the intracellular innate immune sensor Nlrp3, resulting in
      caspase-1 activation and production of proinflammatory cytokines IL-1beta and IL
      18. Here, we showed that mice deficient in Nlrp3, apoptosis-associated speck-like
      protein, and caspase-1 were resistant to the development of high-fat diet-induced
      obesity, which correlated with protection from obesity-induced insulin
      resistance. Furthermore, hepatic triglyceride content, adipocyte size, and
      macrophage infiltration in adipose tissue were all reduced in mice deficient in
      inflammasome components. Monocyte chemoattractant protein (MCP)-1 is a key
      molecule that mediates macrophage infiltration. Indeed, defective inflammasome
      activation was associated with reduced MCP-1 production in adipose tissue.
      Furthermore, plasma leptin and resistin that affect energy use and insulin
      sensitivity were also changed by inflammasome-deficiency. Detailed metabolic and
      molecular phenotyping demonstrated that the inflammasome controls energy
      expenditure and adipogenic gene expression during chronic overfeeding. These
      findings reveal a critical function of the inflammasome in obesity and insulin
      resistance, and suggest inhibition of the inflammasome as a potential therapeutic
      strategy.

PMID- 21876128
TI  - Convergent evolution of two mammalian neuronal enhancers by sequential exaptation
      of unrelated retroposons.
AB  - The proopiomelanocortin gene (POMC) is expressed in a group of neurons present in
      the arcuate nucleus of the hypothalamus. Neuron-specific POMC expression in
      mammals is conveyed by two distal enhancers, named nPE1 and nPE2. Previous
      transgenic mouse studies showed that nPE1 and nPE2 independently drive reporter
      gene expression to POMC neurons. Here, we investigated the evolutionary
      mechanisms that shaped not one but two neuron-specific POMC enhancers and tested
      whether nPE1 and nPE2 drive identical or complementary spatiotemporal expression
      patterns. Sequence comparison among representative genomes of most vertebrate
      classes and mammalian orders showed that nPE1 is a placental novelty. Using in
      silico paleogenomics we found that nPE1 originated from the exaptation of a
      mammalian-apparent LTR retrotransposon sometime between the metatherian/eutherian
      split (147 Mya) and the placental mammal radiation (~ 90 Mya). Thus, the
      evolutionary origin of nPE1 differs, in kind and time, from that previously
      demonstrated for nPE2, which was exapted from a CORE-short interspersed
      nucleotide element (SINE) retroposon before the origin of prototherians, 166 Mya.
      Transgenic mice expressing the fluorescent markers tomato and EGFP driven by nPE1
      or nPE2, respectively, demonstrated coexpression of both reporter genes along the
      entire arcuate nucleus. The onset of reporter gene expression guided by nPE1 and
      nPE2 was also identical and coincidental with the onset of Pomc expression in the
      presumptive mouse diencephalon. Thus, the independent exaptation of two unrelated
      retroposons into functional analogs regulating neuronal POMC expression
      constitutes an authentic example of convergent molecular evolution of cell
      specific enhancers.

PMID- 21876129
TI  - Role of stochastic processes in maintaining discrete strain structure in
      antigenically diverse pathogen populations.
AB  - Many highly diverse pathogen populations appear to exist stably as discrete
      antigenic types despite evidence of genetic exchange. It has been shown that this
      may arise as a consequence of immune selection on pathogen populations, causing
      them to segregate permanently into discrete nonoverlapping subsets of antigenic
      variants to minimize competition for available hosts. However, discrete antigenic
      strain structure tends to break down under conditions where there are unequal
      numbers of allelic variants at each locus. Here, we show that the inclusion of
      stochastic processes can lead to the stable recovery of discrete strain structure
      through loss of certain alleles. This explains how pathogen populations may
      continue to behave as independently transmitted strains despite inevitable
      asymmetries in allelic diversity of major antigens. We present evidence for this
      type of structuring across global meningococcal isolates in three diverse
      antigens that are currently being developed as vaccine components.

PMID- 21876131
TI  - Reconstruction of a 1,910-y-long locust series reveals consistent associations
      with climate fluctuations in China.
AB  - It is becoming increasingly clear that global warming is taking place; however,
      its long-term effects on biological populations are largely unknown due to lack
      of long-term data. Here, we reconstructed a 1,910-y-long time series of outbreaks
      of Oriental migratory locusts (Locusta migratoria manilensis) in China, on the
      basis of information extracted from >8,000 historical documents. First by
      analyzing the most recent period with the best data quality using generalized
      additive models, we found statistically significant associations between the
      reconstructed locust abundance and indexes of precipitation and temperature at
      both annual (A.D. 1512-1911) and decadal (A.D. 1000-1900) scales: There were more
      locusts under dry and cold conditions and when locust abundance was high in the
      preceding year or decade. Second, by exploring locust-environment correlations
      using a 200-y moving window, we tested whether these associations also hold
      further back in time. The locust-precipitation correlation was found to hold at
      least as far back as to A.D. 500, supporting the robustness of this link as well
      as the quality of both reconstructions. The locust-temperature correlation was
      weaker and less consistent, which may reflect this link being indirect and thus
      more easily moderated by other factors. We anticipate that further analysis of
      this unique time series now available to the scientific community will continue
      to provide insights into biological consequences of climate change in the years
      to come.

PMID- 21876130
TI  - The mammalian target of rapamycin regulates cholesterol biosynthetic gene
      expression and exhibits a rapamycin-resistant transcriptional profile.
AB  - The mammalian target of rapamycin (mTOR) is a central regulator of cell growth
      and proliferation in response to growth factor and nutrient signaling.
      Consequently, this kinase is implicated in metabolic diseases including cancer
      and diabetes, so there is great interest in understanding the complete spectrum
      of mTOR-regulated networks. mTOR exists in two functionally distinct complexes,
      mTORC1 and mTORC2, and whereas the natural product rapamycin inhibits only a
      subset of mTORC1 functions, recently developed ATP-competitive mTOR inhibitors
      have revealed new roles for both complexes. A number of studies have highlighted
      mTORC1 as a regulator of lipid homeostasis. We show that the ATP-competitive
      inhibitor PP242, but not rapamycin, significantly down-regulates cholesterol
      biosynthesis genes in a 4E-BP1-dependent manner in NIH 3T3 cells, whereas S6
      kinase 1 is the dominant regulator in hepatocellular carcinoma cells. To identify
      other rapamycin-resistant transcriptional outputs of mTOR, we compared the
      expression profiles of NIH 3T3 cells treated with rapamycin versus PP242. PP242
      caused 1,666 genes to be differentially expressed whereas rapamycin affected only
      88 genes. Our analysis provides a genomewide view of the transcriptional outputs
      of mTOR signaling that are insensitive to rapamycin.

PMID- 21876132
TI  - Differential radial capillary action of ligand assay for high-throughput
      detection of protein-metabolite interactions.
AB  - Interactions of proteins with low-molecular-weight ligands, such as metabolites,
      cofactors, and allosteric regulators, are important determinants of metabolism,
      gene regulation, and cellular homeostasis. Pharmaceuticals often target these
      interactions to interfere with regulatory pathways. We have developed a rapid,
      precise, and high-throughput method for quantitatively measuring protein-ligand
      interactions without the need to purify the protein when performed in cells with
      low background activity. This method, differential radial capillary action of
      ligand assay (DRaCALA), is based on the ability of dry nitrocellulose to separate
      the free ligand from bound protein-ligand complexes. Nitrocellulose sequesters
      proteins and bound ligand at the site of application, whereas free ligand is
      mobilized by bulk movement of the solvent through capillary action. We show here
      that DRaCALA allows detection of specific interactions between three nucleotides
      and their cognate binding proteins. DRaCALA allows quantitative measurement of
      the dissociation constant and the dissociation rate. Furthermore, DRaCALA can
      detect the expression of a cyclic-di-GMP (cdiGMP)-binding protein in whole-cell
      lysates of Escherichia coli, demonstrating the power of the method to bypass the
      prerequisite for protein purification. We have used DRaCALA to investigate cdiGMP
      signaling in 54 bacterial species from 37 genera and 7 eukaryotic species. These
      studies revealed the presence of potential cdiGMP-binding proteins in 21 species
      of bacteria, including 4 unsequenced species. The ease of obtaining metabolite
      protein interaction data using the DRaCALA assay will facilitate rapid
      identification of protein-metabolite and protein-pharmaceutical interactions in a
      systematic and comprehensive approach.

PMID- 21876133
TI  - Herd behavior in a complex adaptive system.
AB  - In order to survive, self-serving agents in various kinds of complex adaptive
      systems (CASs) must compete against others for sharing limited resources with
      biased or unbiased distribution by conducting strategic behaviors. This
      competition can globally result in the balance of resource allocation. As a
      result, most of the agents and species can survive well. However, it is a common
      belief that the formation of a herd in a CAS will cause excess volatility, which
      can ruin the balance of resource allocation in the CAS. Here this belief is
      challenged with the results obtained from a modeled resource-allocation system.
      Based on this system, we designed and conducted a series of computer-aided human
      experiments including herd behavior. We also performed agent-based simulations
      and theoretical analyses, in order to confirm the experimental observations and
      reveal the underlying mechanism. We report that, as long as the ratio of the two
      resources for allocation is biased enough, the formation of a typically sized
      herd can help the system to reach the balanced state. This resource ratio also
      serves as the critical point for a class of phase transition identified herein,
      which can be used to discover the role change of herd behavior, from a ruinous
      one to a helpful one. This work is also of value to some fields, ranging from
      management and social science, to ecology and evolution, and to physics.

PMID- 21876134
TI  - Heterotrimeric G protein beta1gamma2 subunits change orientation upon complex
      formation with G protein-coupled receptor kinase 2 (GRK2) on a model membrane.
AB  - Few experimental techniques can assess the orientation of peripheral membrane
      proteins in their native environment. Sum Frequency Generation (SFG) vibrational
      spectroscopy was applied to study the formation of the complex between G protein
      coupled receptor (GPCR) kinase 2 (GRK2) and heterotrimeric G protein
      beta(1)gamma(2) subunits (Gbetagamma) at a lipid bilayer, without any exogenous
      labels. The most likely membrane orientation of the GRK2-Gbetagamma complex
      differs from that predicted from the known protein crystal structure, and
      positions the predicted receptor docking site of GRK2 such that it would more
      optimally interact with GPCRs. Gbetagamma also appears to change its orientation
      after binding to GRK2. The developed methodology is widely applicable for the
      study of other membrane proteins in situ.

PMID- 21876135
TI  - Lack of confidence in approximate Bayesian computation model choice.
AB  - Approximate Bayesian computation (ABC) have become an essential tool for the
      analysis of complex stochastic models. Grelaud et al. [(2009) Bayesian Anal 3:427
      442] advocated the use of ABC for model choice in the specific case of Gibbs
      random fields, relying on an intermodel sufficiency property to show that the
      approximation was legitimate. We implemented ABC model choice in a wide range of
      phylogenetic models in the Do It Yourself-ABC (DIY-ABC) software [Cornuet et al.
      (2008) Bioinformatics 24:2713-2719]. We now present arguments as to why the
      theoretical arguments for ABC model choice are missing, because the algorithm
      involves an unknown loss of information induced by the use of insufficient
      summary statistics. The approximation error of the posterior probabilities of the
      models under comparison may thus be unrelated with the computational effort spent
      in running an ABC algorithm. We then conclude that additional empirical
      verifications of the performances of the ABC procedure as those available in DIY
      ABC are necessary to conduct model choice.

PMID- 21876137
TI  - Implications for the hydrologic cycle under climate change due to the expansion
      of bioenergy crops in the Midwestern United States.
AB  - To meet emerging bioenergy demands, significant areas of the large-scale
      agricultural landscape of the Midwestern United States could be converted to
      second generation bioenergy crops such as miscanthus and switchgrass. The high
      biomass productivity of bioenergy crops in a longer growing season linked tightly
      to water use highlight the potential for significant impact on the hydrologic
      cycle in the region. This issue is further exacerbated by the uncertainty in the
      response of the vegetation under elevated CO(2) and temperature. We use a
      mechanistic multilayer canopy-root-soil model to (i) capture the eco
      physiological acclimations of bioenergy crops under climate change, and (ii)
      predict how hydrologic fluxes are likely to be altered from their current
      magnitudes. Observed data and Monte Carlo simulations of weather for recent past
      and future scenarios are used to characterize the variability range of the
      predictions. Under present weather conditions, miscanthus and switchgrass
      utilized more water than maize for total seasonal evapotranspiration by
      approximately 58% and 36%, respectively. Projected higher concentrations of
      atmospheric CO(2) (550 ppm) is likely to decrease water used for
      evapotranspiration of miscanthus, switchgrass, and maize by 12%, 10%, and 11%,
      respectively. However, when climate change with projected increases in air
      temperature and reduced summer rainfall are also considered, there is a net
      increase in evapotranspiration for all crops, leading to significant reduction in
      soil-moisture storage and specific surface runoff. These results highlight the
      critical role of the warming climate in potentially altering the water cycle in
      the region under extensive conversion of existing maize cropping to support
      bioenergy demand.

PMID- 21876136
TI  - Bayesian design of synthetic biological systems.
AB  - Here we introduce a new design framework for synthetic biology that exploits the
      advantages of Bayesian model selection. We will argue that the difference between
      inference and design is that in the former we try to reconstruct the system that
      has given rise to the data that we observe, whereas in the latter, we seek to
      construct the system that produces the data that we would like to observe, i.e.,
      the desired behavior. Our approach allows us to exploit methods from Bayesian
      statistics, including efficient exploration of models spaces and high-dimensional
      parameter spaces, and the ability to rank models with respect to their ability to
      generate certain types of data. Bayesian model selection furthermore
      automatically strikes a balance between complexity and (predictive or
      explanatory) performance of mathematical models. To deal with the complexities of
      molecular systems we employ an approximate Bayesian computation scheme which only
      requires us to simulate from different competing models to arrive at rational
      criteria for choosing between them. We illustrate the advantages resulting from
      combining the design and modeling (or in silico prototyping) stages currently
      seen as separate in synthetic biology by reference to deterministic and
      stochastic model systems exhibiting adaptive and switch-like behavior, as well as
      bacterial two-component signaling systems.

PMID- 21876138
TI  - Mathematical accuracy of Aztec land surveys assessed from records in the Codex
      Vergara.
AB  - Land surveying in ancient states is documented not only for Eurasia but also for
      the Americas, amply attested by two Acolhua-Aztec pictorial manuscripts from the
      Valley of Mexico. The Codex Vergara and the Codice de Santa Maria Asuncion
      consist of hundreds of drawings of agricultural fields that uniquely record
      surface areas as well as perimeter measurements. A previous study of the Codex
      Vergara examines how Acolhua-Aztecs determined field area by reconstructing their
      calculation procedures. Here we evaluate the accuracy of their area values using
      modern mathematics. The findings verify the overall mathematical validity of the
      codex records. Three-quarters of the areas are within 5% of the maximum possible
      value, and 85% are within 10%, which compares well with reported errors by
      Western surveyors that postdate Aztec-Acolhua work by several centuries.

PMID- 21876139
TI  - Mechanical regulation of vascular growth and tissue regeneration in vivo.
AB  - New vascular network formation is a critical step in the wound healing process
      and a primary limiting factor in functional tissue regeneration. Like many
      tissues, neovascular networks have been shown in vitro to be highly sensitive to
      mechanical conditions; however, the effects of matrix deformations on neovascular
      network formation and remodeling in engineered tissue regeneration in vivo have
      not been evaluated. We quantified the effects of early and delayed functional
      loading on neovascular growth in a rat model of large bone defect regeneration
      using compliant fixation plates that were unlocked to allow transfer of
      ambulatory loads to the defect either at the time of implantation (early), or
      after 4 wk of stiff fixation (delayed). Neovascular growth and bone regeneration
      were quantitatively evaluated 3 wk after the onset of loading by contrast
      enhanced microcomputed tomography and histology. The initial vascular response to
      bone injury featured robust angiogenesis and collateral vessel formation,
      increasing parameters such as vascular volume and connectivity while decreasing
      degree of anisotropy. Application of early mechanical loading significantly
      inhibited vascular invasion into the defect by 66% and reduced bone formation by
      75% in comparison to stiff plate controls. In contrast, delaying the onset of
      loading by 4 wk significantly enhanced bone formation by 20% and stimulated
      vascular remodeling by increasing the number of large vessels and decreasing the
      number of small vessels. Together, these data demonstrate the mechanosensitivity
      of neovascular networks and highlight the capacity of biomechanical stimulation
      to modulate postnatal vascular growth and remodeling.

PMID- 21876140
TI  - Large collective motions regulate the functional properties of glutamate
      transporter trimers.
AB  - Glutamate transporters clear synaptically released glutamate to maintain precise
      communication between neurons and limit glutamate neurotoxicity. Although much
      progress has been made on the topology, structure, and function of these
      carriers, few studies have addressed large-scale structural motions collectively
      associated with substrate transport. Here we show that a series of single
      cysteine substitutions in the helical hairpin HP2 of excitatory amino acid
      transporter 1 form intersubunit disulfide cross-links within the trimer. After
      cross-linking, substrate uptake, but not substrate-activated anion conductance,
      is completely inhibited in these mutants. These disulfide bridges link residue
      pairs > 40 A apart in the outward-facing crystal structure, and can be explained
      by concerted subunit movements predicted by the anisotropic network model (ANM).
      The existence of these global motions is further supported by the observation
      that single cysteine substitutions at the extracellular part of the transmembrane
      domain 8 can also be cross-linked by copper phenanthroline as predicted by the
      ANM. Interestingly, the transport domain in the un-cross-linked subunit of the
      trimer assumes an inward-facing orientation, suggesting that individual subunits
      potentially undergo separate transitions between outward- and inward-facing
      forms, rather than an all-or-none transition of the three subunits, a mechanism
      also supported by ANM-predicted intrinsic dynamics. These results shed light on
      how large collective motions contribute to the functional dynamics of glutamate
      transporters.

PMID- 21876141
TI  - On the spontaneous collective motion of active matter.
AB  - Spontaneous directed motion, a hallmark of cell biology, is unusual in classical
      statistical physics. Here we study, using both numerical and analytical methods,
      organized motion in models of the cytoskeleton in which constituents are driven
      by energy-consuming motors. Although systems driven by small-step motors are
      described by an effective temperature and are thus quiescent, at higher order in
      step size, both homogeneous and inhomogeneous, flowing and oscillating behavior
      emerges. Motors that respond with a negative susceptibility to imposed forces
      lead to an apparent negative-temperature system in which beautiful structures
      form resembling the asters seen in cell division.

PMID- 21876142
TI  - Correlation of in situ mechanosensitive responses of the Moraxella catarrhalis
      adhesin UspA1 with fibronectin and receptor CEACAM1 binding.
AB  - Bacterial cell surfaces are commonly decorated with a layer formed from multiple
      copies of adhesin proteins whose binding interactions initiate colonization and
      infection processes. In this study, we investigate the physical deformability of
      the UspA1 adhesin protein from Moraxella catarrhalis, a causative agent of middle
      ear infections in humans. UspA1 binds a range of extracellular proteins including
      fibronectin, and the epithelial cellular receptor carcinoembryonic antigen
      related cell adhesion molecule 1 (CEACAM1). Electron microscopy indicates that
      unliganded UspA1 is densely packed at, and extends about 800 A from, the
      Moraxella surface. Using a modified atomic force microscope, we show that the
      adhesive properties and thickness of the UspA1 layer at the cell surface varies
      on addition of either fibronectin or CEACAM1. This in situ analysis is then
      correlated with the molecular structure of UspA1. To provide an overall model for
      UspA1, we have determined crystal structures for two N-terminal fragments which
      are then combined with a previous structure of the CEACAM1-binding site. We show
      that the UspA1-fibronectin complex is formed between UspA1 head region and the
      13th type-III domain of fibronectin and, using X-ray scattering, that the complex
      involves an angular association between these two proteins. In combination with a
      previous study, which showed that the CEACAM1-UspA1 complex is distinctively bent
      in solution, we correlate these observations on isolated fragments of UspA1 with
      its in situ response on the cell surface. This study therefore provides a rare
      direct demonstration of protein conformational change at the cell surface.

PMID- 21876143
TI  - Controlling the dimensionality of charge transport in organic thin-film
      transistors.
AB  - Electrolyte-gated organic thin-film transistors (OTFTs) can offer a feasible
      platform for future flexible, large-area and low-cost electronic applications.
      These transistors can be divided into two groups on the basis of their operation
      mechanism: (i) field-effect transistors that switch fast but carry much less
      current than (ii) the electrochemical transistors which, on the contrary, switch
      slowly. An attractive approach would be to combine the benefits of the field
      effect and the electrochemical transistors into one transistor that would both
      switch fast and carry high current densities. Here we report the development of a
      polyelectrolyte-gated OTFT based on conjugated polyelectrolytes, and we
      demonstrate that the OTFTs can be controllably operated either in the field
      effect or the electrochemical regime. Moreover, we show that the extent of
      electrochemical doping can be restricted to a few monolayers of the conjugated
      polyelectrolyte film, which allows both high current densities and fast switching
      speeds at the same time. We propose an operation mechanism based on self-doping
      of the conjugated polyelectrolyte backbone by its ionic side groups.

PMID- 21876144
TI  - Interaction of complexes I, III, and IV within the bovine respirasome by single
      particle cryoelectron tomography.
AB  - The respirasome is a multisubunit supercomplex of the respiratory chain in
      mitochondria. Here we report the 3D reconstruction of the bovine heart
      respirasome, composed of dimeric complex III and single copies of complex I and
      IV, at about 2.2-nm resolution, determined by cryoelectron tomography and
      subvolume averaging. Fitting of X-ray structures of single complexes I, III(2),
      and IV with high fidelity allows interpretation of the model at the level of
      secondary structures and shows how the individual complexes interact within the
      respirasome. Surprisingly, the distance between cytochrome c binding sites of
      complexes III(2) and IV is about 10 nm. Modeling indicates a loose interaction
      between the three complexes and provides evidence that lipids are gluing them at
      the interfaces.

PMID- 21876145
TI  - Insights into Krabbe disease from structures of galactocerebrosidase.
AB  - Krabbe disease is a devastating neurodegenerative disease characterized by
      widespread demyelination that is caused by defects in the enzyme
      galactocerebrosidase (GALC). Disease-causing mutations have been identified
      throughout the GALC gene. However, a molecular understanding of the effect of
      these mutations has been hampered by the lack of structural data for this enzyme.
      Here we present the crystal structures of GALC and the GALC-product complex,
      revealing a novel domain architecture with a previously uncharacterized lectin
      domain not observed in other hydrolases. All three domains of GALC contribute
      residues to the substrate-binding pocket, and disease-causing mutations are
      widely distributed throughout the protein. Our structures provide an essential
      insight into the diverse effects of pathogenic mutations on GALC function in
      human Krabbe variants and a compelling explanation for the severity of many
      mutations associated with fatal infantile disease. The localization of disease
      associated mutations in the structure of GALC will facilitate identification of
      those patients that would be responsive to pharmacological chaperone therapies.
      Furthermore, our structure provides the atomic framework for the design of such
      drugs.

PMID- 21876146
TI  - Mapping the receptor site for alpha-scorpion toxins on a Na+ channel voltage
      sensor.
AB  - The alpha-scorpions toxins bind to the resting state of Na(+) channels and
      inhibit fast inactivation by interaction with a receptor site formed by domains I
      and IV. Mutants T1560A, F1610A, and E1613A in domain IV had lower affinities for
      Leiurus quinquestriatus hebraeus toxin II (LqhII), and mutant E1613R had ~73-fold
      lower affinity. Toxin dissociation was accelerated by depolarization and
      increased by these mutations, whereas association rates at negative membrane
      potentials were not changed. These results indicate that Thr1560 in the S1-S2
      loop, Phe1610 in the S3 segment, and Glu1613 in the S3-S4 loop in domain IV
      participate in toxin binding. T393A in the SS2-S6 loop in domain I also had lower
      affinity for LqhII, indicating that this extracellular loop may form a secondary
      component of the receptor site. Analysis with the Rosetta-Membrane algorithm
      resulted in a model of LqhII binding to the voltage sensor in a resting state, in
      which amino acid residues in an extracellular cleft formed by the S1-S2 and S3-S4
      loops in domain IV interact with two faces of the wedge-shaped LqhII molecule.
      The conserved gating charges in the S4 segment are in an inward position and form
      ion pairs with negatively charged amino acid residues in the S2 and S3 segments
      of the voltage sensor. This model defines the structure of the resting state of a
      voltage sensor of Na(+) channels and reveals its mode of interaction with a
      gating modifier toxin.

PMID- 21876147
TI  - Two types of cis-trans compensation in the evolution of transcriptional
      regulation.
AB  - Because distant species often share similar macromolecules, regulatory mutations
      are often considered responsible for much of their biological differences.
      Recently, a large portion of regulatory changes has been attributed to cis
      regulatory mutations. Here, we examined an alternative possibility that the
      putative contribution of cis-regulatory changes was, in fact, caused by
      compensatory action of cis- and trans-regulatory elements. First, we show by
      stochastic simulations that compensatory cis-trans evolution maintains the
      binding affinity of a transcription factor at a constant level, thereby
      spuriously exaggerating the contribution of cis-regulatory mutations to gene
      expression divergence. This exaggeration was not observed when changes in the
      binding affinity were compensated by variable transcription factor concentration.
      Second, using reciprocal introgressions of Drosophila, we show that relative
      expression of heterozygous alleles from two distinct species often varied
      significantly between different species backgrounds, indicating the possible
      action of cis-trans compensation. Taken together, we propose that cis-trans
      hybrid incompatibilities are accumulating much faster than generally considered.

PMID- 21876148
TI  - Cross-modal responses in the primary visual cortex encode complex objects and
      correlate with tactile discrimination.
AB  - Cortical areas that directly receive sensory inputs from the thalamus were long
      thought to be exclusively dedicated to a single modality, originating separate
      labeled lines. In the past decade, however, several independent lines of research
      have demonstrated cross-modal responses in primary sensory areas. To investigate
      whether these responses represent behaviorally relevant information, we carried
      out neuronal recordings in the primary somatosensory cortex (S1) and primary
      visual cortex (V1) of rats as they performed whisker-based tasks in the dark.
      During the free exploration of novel objects, V1 and S1 responses carried
      comparable amounts of information about object identity. During execution of an
      aperture tactile discrimination task, tactile recruitment was slower and less
      robust in V1 than in S1. However, V1 tactile responses correlated significantly
      with performance across sessions. Altogether, the results support the notion that
      primary sensory areas have a preference for a given modality but can engage in
      meaningful cross-modal processing depending on task demand.

PMID- 21876149
TI  - Formation of plant metabolic gene clusters within dynamic chromosomal regions.
AB  - In bacteria, genes with related functions often are grouped together in operons
      and are cotranscribed as a single polycistronic mRNA. In eukaryotes, functionally
      related genes generally are scattered across the genome. Notable exceptions
      include gene clusters for catabolic pathways in yeast, synthesis of secondary
      metabolites in filamentous fungi, and the major histocompatibility complex in
      animals. Until quite recently it was thought that gene clusters in plants were
      restricted to tandem duplicates (for example, arrays of leucine-rich repeat
      disease-resistance genes). However, operon-like clusters of coregulated
      nonhomologous genes are an emerging theme in plant biology, where they may be
      involved in the synthesis of certain defense compounds. These clusters are
      unlikely to have arisen by horizontal gene transfer, and the mechanisms behind
      their formation are poorly understood. Previously in thale cress (Arabidopsis
      thaliana) we identified an operon-like gene cluster that is required for the
      synthesis and modification of the triterpene thalianol. Here we characterize a
      second operon-like triterpene cluster (the marneral cluster) from A. thaliana,
      compare the features of these two clusters, and investigate the evolutionary
      events that have led to cluster formation. We conclude that common mechanisms are
      likely to underlie the assembly and control of operon-like gene clusters in
      plants.

PMID- 21876150
TI  - Ingestion of Lactobacillus strain regulates emotional behavior and central GABA
      receptor expression in a mouse via the vagus nerve.
AB  - There is increasing, but largely indirect, evidence pointing to an effect of
      commensal gut microbiota on the central nervous system (CNS). However, it is
      unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a
      direct effect on neurotransmitter receptors in the CNS in normal, healthy
      animals. GABA is the main CNS inhibitory neurotransmitter and is significantly
      involved in regulating many physiological and psychological processes.
      Alterations in central GABA receptor expression are implicated in the
      pathogenesis of anxiety and depression, which are highly comorbid with functional
      bowel disorders. In this work, we show that chronic treatment with L. rhamnosus
      (JB-1) induced region-dependent alterations in GABA(B1b) mRNA in the brain with
      increases in cortical regions (cingulate and prelimbic) and concomitant
      reductions in expression in the hippocampus, amygdala, and locus coeruleus, in
      comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced
      GABA(Aalpha2) mRNA expression in the prefrontal cortex and amygdala, but
      increased GABA(Aalpha2) in the hippocampus. Importantly, L. rhamnosus (JB-1)
      reduced stress-induced corticosterone and anxiety- and depression-related
      behavior. Moreover, the neurochemical and behavioral effects were not found in
      vagotomized mice, identifying the vagus as a major modulatory constitutive
      communication pathway between the bacteria exposed to the gut and the brain.
      Together, these findings highlight the important role of bacteria in the
      bidirectional communication of the gut-brain axis and suggest that certain
      organisms may prove to be useful therapeutic adjuncts in stress-related disorders
      such as anxiety and depression.

PMID- 21876151
TI  - Newly discovered landscape traps produce regime shifts in wet forests.
AB  - We describe the "landscape trap" concept, whereby entire landscapes are shifted
      into, and then maintained (trapped) in, a highly compromised structural and
      functional state as the result of multiple temporal and spatial feedbacks between
      human and natural disturbance regimes. The landscape trap concept builds on ideas
      like stable alternative states and other relevant concepts, but it substantively
      expands the conceptual thinking in a number of unique ways. In this paper, we (i)
      review the literature to develop the concept of landscape traps, including their
      general features; (ii) provide a case study as an example of a landscape trap
      from the mountain ash (Eucalyptus regnans) forests of southeastern Australia;
      (iii) suggest how landscape traps can be detected before they are irrevocably
      established; and (iv) present evidence of the generality of landscape traps in
      different ecosystems worldwide.

PMID- 21876152
TI  - PI3K-targeted therapy can be evaded by gene amplification along the MYC
      eukaryotic translation initiation factor 4E (eIF4E) axis.
AB  - The PI3K pathway is frequently activated in cancer; therefore, considerable
      effort is focused on identifying compounds that can inhibit specific pathway
      components, particularly the hallmark oncogene PIK3CA. Although targeted
      inhibition of a cancer survival gene holds significant promise, there are
      concerns that drug resistance may emerge within the cancerous cells, thus
      limiting clinical efficacy. Using genetically defined human mammary epithelial
      cells, we evolved resistance to the PI3K/mammalian target of rapamycin (mTOR)
      inhibitor BEZ235, and by genome-wide copy number analyses, we identified MYC and
      eIF4E amplification within the resistant cells. Importantly, either MYC or
      eukaryotic translation initiation factor 4E (eIF4E) was required to bypass
      pharmacological PI3K/mTOR inhibition in resistant cells. Furthermore, these cells
      displayed elevated 5' cap-dependent protein translation. Collectively, these
      findings suggest that analysis of drivers of protein translation could facilitate
      the identification of cancer lesions that confer resistance to PI3K pathway
      targeted drugs.

PMID- 21876153
TI  - Complementary roles of Fas-associated death domain (FADD) and receptor
      interacting protein kinase-3 (RIPK3) in T-cell homeostasis and antiviral
      immunity.
AB  - Caspase-8 (casp8) is required for extrinsic apoptosis, and mice deficient in
      casp8 fail to develop and die in utero while ultimately failing to maintain the
      proliferation of T cells, B cells, and a host of other cell types. Paradoxically,
      these failures are not caused by a defect in apoptosis, but by a presumed
      proliferative function of this protease. Indeed, following mitogenic stimulation,
      T cells lacking casp8 or its adaptor protein FADD (Fas-associated death domain
      protein) develop a hyperautophagic morphology, and die a programmed necrosis-like
      death process termed necroptosis. Recent studies have demonstrated that receptor
      interacting protein kinases (RIPKs) RIPK1 and RIPK3 together facilitate TNF
      induced necroptosis, but the precise role of RIPKs in the demise of T cells
      lacking FADD or casp8 activity is unknown. Here we demonstrate that RIPK3 and
      FADD have opposing and complementary roles in promoting T-cell clonal expansion
      and homeostasis. We show that the defective proliferation of T cells bearing an
      interfering form of FADD (FADDdd) is rescued by crossing with RIPK3(-/-) mice,
      although such rescue ultimately leads to lymphadenopathy. Enhanced recovery of
      these double-mutant T cells following stimulation demonstrates that FADD, casp8,
      and RIPK3 are all essential for clonal expansion, contraction, and antiviral
      responses. Finally, we demonstrate that caspase-mediated cleavage of RIPK1
      containing necrosis inducing complexes (necrosomes) is sufficient to prevent
      necroptosis in the face of death receptor signaling. These studies highlight the
      "two-faced" nature of casp8 activity, promoting clonal expansion in some
      situations and apoptotic demise in others.

PMID- 21876154
TI  - Context-dependent individualization of nucleotides and virtual genomic
      hybridization allow the precise location of human SNPs.
AB  - We have entered the era of individual genomic sequencing, and can already see
      exponential progress in the field. It is of utmost importance to exclude false
      positive variants from reported datasets. However, because of the nature of the
      used algorithms, this task has not been optimized to the required level of
      precision. This study presents a unique strategy for identifying SNPs, called
      COIN-VGH, that largely minimizes the presence of false-positives in the generated
      data. The algorithm was developed using the X-chromosome-specific regions from
      the previously sequenced genomes of Craig Venter and James Watson. The algorithm
      is based on the concept that a nucleotide can be individualized if it is analyzed
      in the context of its surrounding genomic sequence. COIN-VGH consists of defining
      the most comprehensive set of nucleotide strings of a defined length that map
      with 100% identity to a unique position within the human reference genome (HRG).
      Such set is used to retrieve sequence reads from a query genome (QG), allowing
      the production of a genomic landscape that represents a draft HRG-guided assembly
      of the QG. This landscape is analyzed for specific signatures that indicate the
      presence of SNPs. The fidelity of the variation signature was assessed using
      simulation experiments by virtually altering the HRG at defined positions.
      Finally, the signature regions identified in the HRG and in the QG reads are
      aligned and the precise nature and position of the corresponding SNPs are
      detected. The advantages of COIN-VGH over previous algorithms are discussed.

PMID- 21876155
TI  - Control of the function of the transcription and repair factor TFIIH by the
      action of the cochaperone Ydj1.
AB  - Yeast rad3-102, a mutant of the TFIIH complex involved in nucleotide excision
      repair (NER) and transcription, can perform NER initial steps but not late steps
      of postincision gap filing. Because removal of early-acting NER proteins prevents
      rad3-102 deleterious action, we used this feature to explore if chaperones act in
      early NER. We found that the cochaperone Ydj1 is required for NER and that Ydj1
      guarantees TFIIH stoichiometry. Importantly, in the absence of Ydj1, the roles of
      TFIIH in transcription and transactivation, the ability to activate transcription
      by nuclear receptors in response to hormones, are strongly impaired. We propose
      that TFIIH constitutes a multitarget complex for Ydj1, as six of the seven TFIIH
      core components contain biologically relevant Ydj1- binding motives. Our results
      provide evidence for a role of chaperones in NER and transcription, with
      implications in cancer and TFIIH-associated syndromes.

PMID- 21876156
TI  - The motor origins of human and avian song structure.
AB  - Human song exhibits great structural diversity, yet certain aspects of melodic
      shape (how pitch is patterned over time) are widespread. These include a
      predominance of arch-shaped and descending melodic contours in musical phrases, a
      tendency for phrase-final notes to be relatively long, and a bias toward small
      pitch movements between adjacent notes in a melody [Huron D (2006) Sweet
      Anticipation: Music and the Psychology of Expectation (MIT Press, Cambridge,
      MA)]. What is the origin of these features? We hypothesize that they stem from
      motor constraints on song production (i.e., the energetic efficiency of their
      underlying motor actions) rather than being innately specified. One prediction of
      this hypothesis is that any animals subject to similar motor constraints on song
      will exhibit similar melodic shapes, no matter how distantly related those
      animals are to humans. Conversely, animals who do not share similar motor
      constraints on song will not exhibit convergent melodic shapes. Birds provide an
      ideal case for testing these predictions, because their peripheral mechanisms of
      song production have both notable similarities and differences from human vocal
      mechanisms [Riede T, Goller F (2010) Brain Lang 115:69-80]. We use these
      similarities and differences to make specific predictions about shared and
      distinct features of human and avian song structure and find that these
      predictions are confirmed by empirical analysis of diverse human and avian song
      samples.

PMID- 21876157
TI  - Low-frequency songs lose their potency in noisy urban conditions.
AB  - Many animal species communicate with their mates through acoustic signals, but
      this communication seems to become a struggle in urbanized areas because of
      increasing anthropogenic noise levels. Several bird species have been reported to
      increase song frequency by which they reduce the masking impact of spectrally
      overlapping noise. However, it remains unclear whether such behavioral
      flexibility provides a sufficient solution to noisy urban conditions or whether
      there are hidden costs. Species may rely on low frequencies to attract and
      impress females, and the use of high frequencies may, therefore, come at the cost
      of reduced attractiveness. We studied the potential tradeoff between signal
      strength and signal detection in a successful urban bird species, the great tit
      (Parus major). We show that the use of low-frequency songs by males is related to
      female fertility as well as sexual fidelity. We experimentally show that urban
      noise conditions impair male-female communication and that signal efficiency
      depends on song frequency in the presence of noise. Our data reveal a response
      advantage for high-frequency songs during sexual signaling in noisy conditions,
      whereas low-frequency songs are likely to be preferred. These data are critical
      for our understanding of the impact of anthropogenic noise on wild-ranging birds,
      because they provide evidence for low-frequency songs being linked to
      reproductive success and to be affected by noise-dependent signal efficiency.

PMID- 21876158
TI  - Intramolecular signal transmission in a tetrameric repressor of the IclR family.
AB  - Members of the IclR family control bacterial genes involved in a number of
      physiological processes. The IclR-family member TtgV crystallizes as a tetramer,
      with each TtgV monomer consisting of two domains--a DNA binding domain and an
      effector recognition domain, which are interconnected by an extended alpha-helix.
      When bound to DNA, a kink is introduced so that the extended helix is split in
      two alpha-helices (helix-4 and -5). Differential scanning calorimetry studies
      revealed that TtgV unfolds in a single event, suggesting that the two domains
      unfold cooperatively. When mutations are introduced in helix-5 that disrupt
      interactions between Arg98 and Glu102, the thermal unfolding of the TtgV domains
      becomes uncoupled without compromising effector binding. Two of these mutants
      (TtgVE102R and TtgVE102A) showed impaired release from target DNA, suggesting
      that these mutations alter signal transmission. By combining various mutants, we
      found that the mutations in the connecting alpha-helix exhibited a dominant
      effect over mutations in DNA binding and effector binding domains. We propose a
      model in which the loss of cooperativity of unfolding of TtgV reflects perturbed
      interdomain communication, and that the transition from the continuous to
      discontinuous helix may mediate interdomain communication necessary for the
      proper functioning of TtgV.

PMID- 21876159
TI  - Nurture affects gender differences in spatial abilities.
AB  - Women remain significantly underrepresented in the science, engineering, and
      technology workforce. Some have argued that spatial ability differences, which
      represent the most persistent gender differences in the cognitive literature, are
      partly responsible for this gap(.) The underlying forces at work shaping the
      observed spatial ability differences revolve naturally around the relative roles
      of nature and nurture. Although these forces remain among the most hotly debated
      in all of the sciences, the evidence for nurture is tenuous, because it is
      difficult to compare gender differences among biologically similar groups with
      distinct nurture. In this study, we use a large-scale incentivized experiment
      with nearly 1,300 participants to show that the gender gap in spatial abilities,
      measured by time to solve a puzzle, disappears when we move from a patrilineal
      society to an adjoining matrilineal society. We also show that about one-third of
      the effect can be explained by differences in education. Given that none of our
      participants have experience with puzzle solving and that villagers from both
      societies have the same means of subsistence and shared genetic background, we
      argue that these results show the role of nurture in the gender gap in cognitive
      abilities.

PMID- 21876160
TI  - Functional characterization of bacterial sRNAs using a network biology approach.
AB  - Small RNAs (sRNAs) are important components of posttranscriptional regulation.
      These molecules are prevalent in bacterial and eukaryotic organisms, and involved
      in a variety of responses to environmental stresses. The functional
      characterization of sRNAs is challenging and requires highly focused and
      extensive experimental procedures. Here, using a network biology approach and a
      compendium of gene expression profiles, we predict functional roles and
      regulatory interactions for sRNAs in Escherichia coli. We experimentally validate
      predictions for three sRNAs in our inferred network: IsrA, GlmZ, and GcvB.
      Specifically, we validate a predicted role for IsrA and GlmZ in the SOS response,
      and we expand on current knowledge of the GcvB sRNA, demonstrating its broad role
      in the regulation of amino acid metabolism and transport. We also show, using the
      inferred network coupled with experiments, that GcvB and Lrp, a transcription
      factor, repress each other in a mutually inhibitory network. This work shows that
      a network-based approach can be used to identify the cellular function of sRNAs
      and characterize the relationship between sRNAs and transcription factors.

PMID- 21876161
TI  - Polyamine catabolism contributes to enterotoxigenic Bacteroides fragilis-induced
      colon tumorigenesis.
AB  - It is estimated that the etiology of 20-30% of epithelial cancers is directly
      associated with inflammation, although the direct molecular events linking
      inflammation and carcinogenesis are poorly defined. In the context of
      gastrointestinal disease, the bacterium enterotoxigenic Bacteroides fragilis
      (ETBF) is a significant source of chronic inflammation and has been implicated as
      a risk factor for colorectal cancer. Spermine oxidase (SMO) is a polyamine
      catabolic enzyme that is highly inducible by inflammatory stimuli resulting in
      increased reactive oxygen species (ROS) and DNA damage. We now demonstrate that
      purified B. fragilis toxin (BFT) up-regulates SMO in HT29/c1 and T84 colonic
      epithelial cells, resulting in SMO-dependent generation of ROS and induction of
      gamma-H2A.x, a marker of DNA damage. Further, ETBF-induced colitis in C57BL/6
      mice is associated with increased SMO expression and treatment of mice with an
      inhibitor of polyamine catabolism, N(1),N(4)-bis(2,3-butandienyl)-1,4
      butanediamine (MDL 72527), significantly reduces ETBF-induced chronic
      inflammation and proliferation. Most importantly, in the multiple intestinal
      neoplasia (Min) mouse model, treatment with MDL 72527 reduces ETBF-induced colon
      tumorigenesis by 69% (P < 0.001). The results of these studies indicate that SMO
      is a source of bacteria-induced ROS directly associated with tumorigenesis and
      could serve as a unique target for chemoprevention.

PMID- 21876162
TI  - Global discovery of small RNAs in Yersinia pseudotuberculosis identifies Yersinia
      specific small, noncoding RNAs required for virulence.
AB  - A major class of bacterial small, noncoding RNAs (sRNAs) acts by base-pairing
      with mRNAs to alter the translation from and/or stability of the transcript. Our
      laboratory has shown that Hfq, the chaperone that mediates the interaction of
      many sRNAs with their targets, is required for the virulence of the
      enteropathogen Yersinia pseudotuberculosis. This finding suggests that sRNAs play
      a critical role in the regulation of virulence in this pathogen, but these sRNAs
      are not known. Using a deep sequencing approach, we identified the global set of
      sRNAs expressed in vitro by Y. pseudotuberculosis. Sequencing of RNA libraries
      from bacteria grown at 26  degrees C and 37  degrees C resulted in the
      identification of 150 unannotated sRNAs. The majority of these sRNAs are Yersinia
      specific, without orthologs in either Escherichia coli or Salmonella typhimurium.
      Six sRNAs are Y. pseudotuberculosis specific and are absent from the genome of
      the closely related species Yersinia pestis. We found that the expression of many
      sRNAs conserved between Y. pseudotuberculosis and Y. pestis differs in both
      timing and dependence on Hfq, suggesting evolutionary changes in
      posttranscriptional regulation between these species. Deletion of multiple sRNAs
      in Y. pseudotuberculosis leads to attenuation of the pathogen in a mouse model of
      yersiniosis, as does the inactivation in Y. pestis of a conserved, Yersinia
      specific sRNA in a mouse model of pneumonic plague. Finally, we determined the
      regulon controlled by one of these sRNAs, revealing potential virulence
      determinants in Y. pseudotuberculosis that are regulated in a posttranscriptional
      manner.

PMID- 21876163
TI  - Forced expression of laminin beta1 in podocytes prevents nephrotic syndrome in
      mice lacking laminin beta2, a model for Pierson syndrome.
AB  - Pierson syndrome is a congenital nephrotic syndrome with ocular and neurological
      defects caused by mutations in LAMB2, the gene encoding the basement membrane
      protein laminin beta2 (Lambeta2). It is the kidney glomerular basement membrane
      (GBM) that is defective in Pierson syndrome, as Lambeta2 is a component of
      laminin-521 (LM-521; alpha5beta2gamma1), the major laminin in the mature GBM. In
      both Pierson syndrome and the Lamb2(-/-) mouse model for this disease, laminin
      beta1 (Lambeta1), a structurally similar homolog of Lambeta2, is marginally
      increased in the GBM, but it fails to fully compensate for the loss of Lambeta2,
      leading to the filtration barrier defects and nephrotic syndrome. Here we
      generated several lines of Lambeta1 transgenic mice and used them to show that
      podocyte-specific Lambeta1 expression in Lamb2(-/-) mice abrogates the
      development of nephrotic syndrome, correlating with a greatly extended lifespan.
      In addition, the more Lambeta1 was expressed, the less urinary albumin was
      excreted. Transgenic Lambeta1 expression increased the level of Lamalpha5 in the
      GBM of rescued mice, consistent with the desired increased deposition of laminin
      511 (alpha5beta1gamma1) trimers. Ultrastructural analysis revealed occasional
      knob-like subepithelial GBM thickening but intact podocyte foot processes in aged
      rescued mice. These results suggest the possibility that up-regulation of LAMB1
      in podocytes, should it become achievable, would likely lessen the severity of
      nephrotic syndrome in patients carrying LAMB2 mutations.

PMID- 21876164
TI  - Insights into the oxidative degradation of cellulose by a copper metalloenzyme
      that exploits biomass components.
AB  - The enzymatic degradation of recalcitrant plant biomass is one of the key
      industrial challenges of the 21st century. Accordingly, there is a continuing
      drive to discover new routes to promote polysaccharide degradation. Perhaps the
      most promising approach involves the application of "cellulase-enhancing
      factors," such as those from the glycoside hydrolase (CAZy) GH61 family. Here we
      show that GH61 enzymes are a unique family of copper-dependent oxidases. We
      demonstrate that copper is needed for GH61 maximal activity and that the
      formation of cellodextrin and oxidized cellodextrin products by GH61 is enhanced
      in the presence of small molecule redox-active cofactors such as ascorbate and
      gallate. By using electron paramagnetic resonance spectroscopy and single-crystal
      X-ray diffraction, the active site of GH61 is revealed to contain a type II
      copper and, uniquely, a methylated histidine in the copper's coordination sphere,
      thus providing an innovative paradigm in bioinorganic enzymatic catalysis.

PMID- 21876165
TI  - Mechanistic basis of bell-shaped dependence of inositol 1,4,5-trisphosphate
      receptor gating on cytosolic calcium.
AB  - The inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) is an intracellular
      Ca(2+) release channel, and its opening is controlled by IP(3) and Ca(2+). A
      single IP(3) binding site and multiple Ca(2+) binding sites exist on single
      subunits, but the precise nature of the interplay between these two ligands in
      regulating biphasic dependence of channel activity on cytosolic Ca(2+) is
      unknown. In this study, we visualized conformational changes in IP(3)R evoked by
      various concentrations of ligands by using the FRET between two fluorescent
      proteins fused to the N terminus of individual subunits. IP(3) and Ca(2+) have
      opposite effects on the FRET signal change, but the combined effect of these
      ligands is not a simple summative response. The bell-shaped Ca(2+) dependence of
      FRET efficiency was observed after the subtraction of the component corresponding
      to the FRET change evoked by Ca(2+) alone from the FRET changes evoked by both
      ligands together. A mutant IP(3)R containing a single amino acid substitution at
      K508, which is critical for IP(3) binding, did not exhibit this bell-shaped
      Ca(2+) dependence of the subtracted FRET efficiency. Mutation at E2100, which is
      known as a Ca(2+) sensor, resulted in ~10-fold reduction in the Ca(2+) dependence
      of the subtracted signal. These results suggest that the subtracted FRET signal
      reflects IP(3)R activity. We propose a five-state model, which implements a dual
      ligand competition response without complex allosteric regulation of Ca(2+)
      binding affinity, as the mechanism underlying the IP(3)-dependent regulation of
      the bell-shaped relationship between the IP(3)R activity and cytosolic Ca(2+).

PMID- 21876166
TI  - Mitochondrial matrix Ca2+ as an intrinsic signal regulating mitochondrial
      motility in axons.
AB  - The proper distribution of mitochondria is particularly vital for neurons because
      of their polarized structure and high energy demand. Mitochondria in axons
      constantly move in response to physiological needs, but signals that regulate
      mitochondrial movement are not well understood. Aside from producing ATP, Ca(2+)
      buffering is another main function of mitochondria. Activities of many enzymes in
      mitochondria are also Ca(2+)-dependent, suggesting that intramitochondrial Ca(2+)
      concentration is important for mitochondrial functions. Here, we report that
      mitochondrial motility in axons is actively regulated by mitochondrial matrix
      Ca(2+). Ca(2+) entry through the mitochondrial Ca(2+) uniporter modulates
      mitochondrial transport, and mitochondrial Ca(2+) content correlates inversely
      with the speed of mitochondrial movement. Furthermore, the miro1 protein plays a
      role in Ca(2+) uptake into the mitochondria, which subsequently affects
      mitochondrial movement.

PMID- 21876167
TI  - Chemical modulation of memory formation in larval zebrafish.
AB  - Whole organism-based small-molecule screens have proven powerful in identifying
      novel therapeutic chemicals, yet this approach has not been exploited to identify
      new cognitive enhancers. Here we present an automated high-throughput system for
      measuring nonassociative learning behaviors in larval zebrafish. Using this
      system, we report that spaced training blocks of repetitive visual stimuli elicit
      protein synthesis-dependent long-term habituation in larval zebrafish, lasting up
      to 24 h. Moreover, repetitive acoustic stimulation induces robust short-term
      habituation that can be modulated by stimulation frequency and instantaneously
      dishabituated through cross-modal stimulation. To characterize the neurochemical
      pathways underlying short-term habituation, we screened 1,760 bioactive compounds
      with known targets. Although we found extensive functional conservation of short
      term learning between larval zebrafish and mammalian models, we also discovered
      several compounds with previously unknown roles in learning. These compounds
      included a myristic acid analog known to interact with Src family kinases and an
      inhibitor of cyclin dependent kinase 2, demonstrating that high-throughput
      chemical screens combined with high-resolution behavioral assays provide a
      powerful approach for the discovery of novel cognitive modulators.

PMID- 21876168
TI  - Fluid forces control endothelial sprouting.
AB  - During angiogenesis, endothelial cells (ECs) from intact blood vessels quickly
      infiltrate avascular regions via vascular sprouting. This process is fundamental
      to many normal and pathological processes such as wound healing and tumor growth,
      but its initiation and control are poorly understood. Vascular endothelial cell
      growth factor (VEGF) can promote vessel dilation and angiogenic sprouting, but
      given the complex nature of vascular morphogenesis, additional signals are likely
      necessary to determine, for example, which vessel segments sprout, which dilate,
      and which remain quiescent. Fluid forces exerted by blood and plasma are prime
      candidates that might codirect these processes, but it is not known whether VEGF
      cooperates with mechanical fluid forces to mediate angiogenesis. Using a
      microfluidic tissue analog of angiogenic sprouting, we found that fluid shear
      stress, such as exerted by flowing blood, attenuates EC sprouting in a nitric
      oxide-dependent manner and that interstitial flow, such as produced by
      extravasating plasma, directs endothelial morphogenesis and sprout formation.
      Furthermore, positive VEGF gradients initiated sprouting but negative gradients
      inhibited sprouting, promoting instead sheet-like migration analogous to vessel
      dilation. These results suggest that ECs integrate signals from fluid forces and
      local VEGF gradients to achieve such varied goals as vessel dilation and
      sprouting.

PMID- 21876169
TI  - Behavioral and neural correlates of delay of gratification 40 years later.
AB  - We examined the neural basis of self-regulation in individuals from a cohort of
      preschoolers who performed the delay-of-gratification task 4 decades ago. Nearly
      60 individuals, now in their mid-forties, were tested on "hot" and "cool"
      versions of a go/nogo task to assess whether delay of gratification in childhood
      predicts impulse control abilities and sensitivity to alluring cues (happy
      faces). Individuals who were less able to delay gratification in preschool and
      consistently showed low self-control abilities in their twenties and thirties
      performed more poorly than did high delayers when having to suppress a response
      to a happy face but not to a neutral or fearful face. This finding suggests that
      sensitivity to environmental hot cues plays a significant role in individuals'
      ability to suppress actions toward such stimuli. A subset of these participants
      (n = 26) underwent functional imaging for the first time to test for biased
      recruitment of frontostriatal circuitry when required to suppress responses to
      alluring cues. Whereas the prefrontal cortex differentiated between nogo and go
      trials to a greater extent in high delayers, the ventral striatum showed
      exaggerated recruitment in low delayers. Thus, resistance to temptation as
      measured originally by the delay-of-gratification task is a relatively stable
      individual difference that predicts reliable biases in frontostriatal circuitries
      that integrate motivational and control processes.

PMID- 21876170
TI  - Dendritic coding of multiple sensory inputs in single cortical neurons in vivo.
AB  - Single cortical neurons in the mammalian brain receive signals arising from
      multiple sensory input channels. Dendritic integration of these afferent signals
      is critical in determining the amplitude and time course of the neurons' output
      signals. As of yet, little is known about the spatial and temporal organization
      of converging sensory inputs. Here, we combined in vivo two-photon imaging with
      whole-cell recordings in layer 2 neurons of the mouse vibrissal cortex as a means
      to analyze the spatial pattern of subthreshold dendritic calcium signals evoked
      by the stimulation of different whiskers. We show that the principle whisker and
      the surrounding whiskers can evoke dendritic calcium transients in the same
      neuron. Distance-dependent attenuation of dendritic calcium transients and the
      corresponding subthreshold depolarization suggest feed-forward activation. We
      found that stimulation of different whiskers produced multiple calcium hotspots
      on the same dendrite. Individual hotspots were activated with low probability in
      a stochastic manner. We show that these hotspots are generated by calcium signals
      arising in dendritic spines. Some spines were activated uniquely by single
      whiskers, but many spines were activated by multiple whiskers. These shared
      spines indicate the existence of presynaptic feeder neurons that integrate and
      transmit activity arising from multiple whiskers. Despite the dendritic overlap
      of whisker-specific and shared inputs, different whiskers are represented by a
      unique set of activation patterns within the dendritic field of each neuron.

PMID- 21876171
TI  - Connective tissue growth factor acts within both endothelial cells and beta cells
      to promote proliferation of developing beta cells.
AB  - Type 1 and type 2 diabetes result from an absolute or relative reduction in
      functional beta-cell mass. One approach to replacing lost beta-cell mass is
      transplantation of cadaveric islets; however, this approach is limited by lack of
      adequate donor tissue. Therefore, there is much interest in identifying factors
      that enhance beta-cell differentiation and proliferation in vivo or in vitro.
      Connective tissue growth factor (CTGF) is a secreted molecule expressed in
      endothelial cells, pancreatic ducts, and embryonic beta cells that we previously
      showed is required for beta-cell proliferation, differentiation, and islet
      morphogenesis during development. The current study investigated the tissue
      interactions by which CTGF promotes normal pancreatic islet development. We found
      that loss of CTGF from either endothelial cells or beta cells results in
      decreased embryonic beta-cell proliferation, making CTGF unique as an identified
      beta cell-derived factor that regulates embryonic beta-cell proliferation.
      Endothelial CTGF inactivation was associated with decreased islet vascularity,
      highlighting the proposed role of endothelial cells in beta-cell proliferation.
      Furthermore, CTGF overexpression in beta cells during embryogenesis using an
      inducible transgenic system increased islet mass at birth by promoting
      proliferation of immature beta cells, in the absence of changes in islet
      vascularity. Together, these findings demonstrate that CTGF acts in an autocrine
      manner during pancreas development and suggest that CTGF has the potential to
      enhance expansion of immature beta cells in directed differentiation or
      regeneration protocols.

PMID- 21876172
TI  - Metabolic basis for the differential susceptibility of Gram-positive pathogens to
      fatty acid synthesis inhibitors.
AB  - The rationale for the pursuit of bacterial type 2 fatty acid synthesis (FASII) as
      a target for antibacterial drug discovery in Gram-positive organisms is being
      debated vigorously based on their ability to incorporate extracellular fatty
      acids. The regulation of FASII by extracellular fatty acids was examined in
      Staphylococcus aureus and Streptococcus pneumoniae, representing two important
      groups of pathogens. Both bacteria use the same enzymatic tool kit for the
      conversion of extracellular fatty acids to acyl-acyl carrier protein, elongation,
      and incorporation into phospholipids. Exogenous fatty acids completely replace
      the endogenous fatty acids in S. pneumoniae but support only 50% of phospholipid
      synthesis in S. aureus. Fatty acids overcame FASII inhibition in S. pneumoniae
      but not in S. aureus. Extracellular fatty acids strongly suppress malonyl-CoA
      levels in S. pneumoniae but not in S. aureus, showing a feedback regulatory
      system in S. pneumoniae that is absent in S. aureus. Fatty acids overcame either
      a biochemical or a genetic block at acetyl-CoA carboxylase (ACC) in S. aureus,
      confirming that regulation at the ACC step is the key difference between these
      two species. Bacteria that possess a stringent biochemical feedback inhibition of
      ACC and malonyl-CoA formation triggered by environmental fatty acids are able to
      circumvent FASII inhibition. However, if exogenous fatty acids do not suppress
      malonyl-CoA formation, FASII inhibitors remain effective in the presence of fatty
      acid supplements.

PMID- 21876173
TI  - Differentiation-dependent functional and epigenetic landscapes for cytokine genes
      in virus-specific CD8+ T cells.
AB  - Although the simultaneous engagement of multiple effector mechanisms is thought
      to characterize optimal CD8(+) T-cell immunity and facilitate pathogen clearance,
      the differentiation pathways leading to the acquisition and maintenance of such
      polyfunctional activity are not well understood. Division-dependent profiles of
      effector molecule expression for virus-specific T cells are analyzed here by
      using a combination of carboxyfluorescein succinimidyl ester dilution and
      intracellular cytokine staining subsequent to T-cell receptor ligation. The
      experiments show that, although the majority of naive CD8(+) T-cell precursors
      are preprogrammed to produce TNF-alpha soon after stimulation and a proportion
      make both TNF-alpha and IL-2, the progressive acquisition of IFN-gamma expression
      depends on continued lymphocyte proliferation. Furthermore, the extensive
      division characteristic of differentiation to peak effector activity is
      associated with the progressive dominance of IFN-gamma and the concomitant loss
      of polyfunctional cytokine production, although this is not apparent for long
      term CD8(+) T-cell memory. Such proliferation-dependent variation in cytokine
      production appears tied to the epigenetic signatures within the ifnG and tnfA
      proximal promoters. Specifically, those cytokine gene loci that are rapidly
      expressed following antigen stimulation at different stages of T-cell
      differentiation can be shown (by ChIP) to have permissive epigenetic and RNA
      polymerase II docking signatures. Thus, the dynamic changes in cytokine profiles
      for naive, effector, and memory T cells are underpinned by specific epigenetic
      landscapes that regulate responsiveness following T-cell receptor ligation.

PMID- 21876174
TI  - Calcium store sensor stromal-interaction molecule 1-dependent signaling plays an
      important role in cervical cancer growth, migration, and angiogenesis.
AB  - Store-operated Ca(2+) entry (SOCE) is the principal Ca(2+) entry mechanism in
      nonexcitable cells. Stromal-interaction molecule 1 (STIM1) is an endoplasmic
      reticulum Ca(2+) sensor that triggers SOCE activation. However, the role of STIM1
      in regulating cancer progression remains controversial and its clinical relevance
      is unclear. Here we show that STIM1-dependent signaling is important for cervical
      cancer cell proliferation, migration, and angiogenesis. STIM1 overexpression in
      tumor tissue is noted in 71% cases of early-stage cervical cancer. In tumor
      tissues, the level of STIM1 expression is significantly associated with the risk
      of metastasis and survival. EGF-stimulated cancer cell migration requires STIM1
      expression and EGF increases the interaction between STIM1 and Orai1 in juxta
      membrane areas, and thus induces Ca(2+) influx. STIM1 involves the activation of
      Ca(2+)-regulated protease calpain, as well as Ca(2+)-regulated cytoplasmic kinase
      Pyk2, which regulate the focal-adhesion dynamics of migratory cervical cancer
      cells. Because of an increase of p21 protein levels and a decrease of Cdc25C
      protein levels, STIM1-silencing in cervical cancer cells significantly inhibits
      cell proliferation by arresting the cell cycle at the S and G2/M phases. STIM1
      also regulates the production of VEGF in cervical cancer cells. Interference with
      STIM1 expression or blockade of SOCE activity inhibits tumor angiogenesis and
      growth in animal models, confirming the crucial role of STIM1-mediated Ca(2+)
      influx in aggravating tumor development in vivo. These results make STIM1
      dependent signaling an attractive target for therapeutic intervention.

PMID- 21876175
TI  - Single cell analysis reveals similar functional competence of dominant and
      nondominant CD8 T-cell clonotypes.
AB  - Immune protection from infectious diseases and cancer is mediated by individual T
      cells of different clonal origin. Their functions are tightly regulated but not
      yet fully characterized. Understanding the contribution of each T cell will
      improve the prediction of immune protection based on laboratory assessment of T
      cell responses. Here we developed techniques for simultaneous molecular and
      functional assessment of single CD8 T cells directly ex vivo. We studied two
      groups of patients with melanoma after vaccination with two closely related tumor
      antigenic peptides. Vaccination induced T cells with strong memory and effector
      functions, as found in virtually all T cells of the first patient group, and
      fractions of T cells in the second group. Interestingly, high functionality was
      not restricted to dominant clonotypes. Rather, dominant and nondominant
      clonotypes acquired equal functional competence. In parallel, this was also found
      for EBV- and CMV-specific T cells. Thus, the nondominant clonotypes may
      contribute similarly to immunity as their dominant counterparts.

PMID- 21876177
TI  - Primordial neurosecretory apparatus identified in the choanoflagellate Monosiga
      brevicollis.
AB  - SNARE protein-driven secretion of neurotransmitters from synaptic vesicles is at
      the center of neuronal communication. In the absence of the cytosolic protein
      Munc18-1, synaptic secretion comes to a halt. Although it is believed that Munc18
      1 orchestrates SNARE complexes, its mode of action is still a matter of debate.
      In particular, it has been challenging to clarify the role of a tight
      Munc18/syntaxin 1 complex, because this interaction interferes strongly with
      syntaxin's ability to form a SNARE complex. In this complex, two regions of
      syntaxin, the N-peptide and the remainder in closed conformation, bind to Munc18
      simultaneously. Until now, this binary complex has been reported for neuronal
      tissues only, leading to the hypothesis that it might be a specialization of the
      neuronal secretion apparatus. Here we aimed, by comparing the core secretion
      machinery of the unicellular choanoflagellate Monosiga brevicollis with that of
      animals, to reconstruct the ancestral function of the Munc18/syntaxin1 complex.
      We found that the Munc18/syntaxin 1 complex from M. brevicollis is structurally
      and functionally highly similar to the vertebrate complex, suggesting that it
      constitutes a fundamental step in the reaction pathway toward SNARE assembly. We
      thus propose that the primordial secretion machinery of the common ancestor of
      choanoflagellates and animals has been co-opted for synaptic roles during the
      rise of animals.

PMID- 21876178
TI  - QnAs with John P. Grotzinger. Interview by Prashant Nair.

PMID- 21876176
TI  - Targeted enrichment of ancient pathogens yielding the pPCP1 plasmid of Yersinia
      pestis from victims of the Black Death.
AB  - Although investigations of medieval plague victims have identified Yersinia
      pestis as the putative etiologic agent of the pandemic, methodological
      limitations have prevented large-scale genomic investigations to evaluate changes
      in the pathogen's virulence over time. We screened over 100 skeletal remains from
      Black Death victims of the East Smithfield mass burial site (1348-1350, London,
      England). Recent methods of DNA enrichment coupled with high-throughput DNA
      sequencing subsequently permitted reconstruction of ten full human mitochondrial
      genomes (16 kb each) and the full pPCP1 (9.6 kb) virulence-associated plasmid at
      high coverage. Comparisons of molecular damage profiles between endogenous human
      and Y. pestis DNA confirmed its authenticity as an ancient pathogen, thus
      representing the longest contiguous genomic sequence for an ancient pathogen to
      date. Comparison of our reconstructed plasmid against modern Y. pestis shows
      identity with several isolates matching the Medievalis biovar; however, our
      chromosomal sequences indicate the victims were infected with a Y. pestis variant
      that has not been previously reported. Our data reveal that the Black Death in
      medieval Europe was caused by a variant of Y. pestis that may no longer exist,
      and genetic data carried on its pPCP1 plasmid were not responsible for the
      purported epidemiological differences between ancient and modern forms of Y.
      pestis infections.

PMID- 21876179
TI  - Zinc-finger antiviral protein inhibits HIV-1 infection by selectively targeting
      multiply spliced viral mRNAs for degradation.
AB  - The zinc-finger antiviral protein (ZAP) was originally identified as a host
      factor that inhibits the replication of Moloney murine leukemia virus. Here we
      report that ZAP inhibits HIV-1 infection by promoting the degradation of specific
      viral mRNAs. Overexpression of ZAP rendered cells resistant to HIV-1 infection in
      a ZAP expression level-dependent manner, whereas depletion of endogenous ZAP
      enhanced HIV-1 infection. Both human and rat ZAP inhibited the propagation of
      replication-competent HIV-1. ZAP specifically targeted the multiply spliced but
      not unspliced or singly spliced HIV-1 mRNAs for degradation. We provide evidence
      indicating that ZAP selectively recruits cellular poly(A)-specific ribonuclease
      (PARN) to shorten the poly(A) tail of target viral mRNA and recruits the RNA
      exosome to degrade the RNA body from the 3' end. In addition, ZAP recruits
      cellular decapping complex through its cofactor RNA helicase p72 to initiate
      degradation of the target viral mRNA from the 5' end. Depletion of each of these
      mRNA degradation enzymes reduced ZAP's activity. Our results indicate that ZAP
      inhibits HIV-1 by recruiting both the 5' and 3' mRNA degradation machinery to
      specifically promote the degradation of multiply spliced HIV-1 mRNAs.

PMID- 21876180
TI  - Thinking outside the box: a lemur's take on hominin craniodental evolution.

PMID- 21876181
TI  - Social influence benefits the wisdom of individuals in the crowd.

PMID- 21876182
TI  - Observation of spatial propagation of amyloid assembly from single nuclei.
AB  - The crucial early stages of amyloid growth, in which normally soluble proteins
      are converted into fibrillar nanostructures, are challenging to study using
      conventional techniques yet are critical to the protein aggregation phenomena
      implicated in many common pathologies. As with all nucleation and growth
      phenomena, it is difficult to track individual nuclei in traditional macroscopic
      experiments, which probe the overall temporal evolution of the sample, but do not
      yield detailed information on the primary nucleation step as they mix independent
      stochastic events into an ensemble measurement. To overcome this limitation, we
      have developed microdroplet assays enabling us to detect single primary
      nucleation events and to monitor their subsequent spatial as well as temporal
      evolution, both of which we find to be determined by secondary nucleation
      phenomena. By deforming the droplets to high aspect ratio, we visualize in real
      time propagating waves of protein assembly emanating from discrete primary
      nucleation sites. We show that, in contrast to classical gelation phenomena, the
      primary nucleation step is characterized by a striking dependence on system size,
      and the filamentous protein self-assembly process involves a highly nonuniform
      spatial distribution of aggregates. These findings deviate markedly from the
      current picture of amyloid growth and uncover a general driving force,
      originating from confinement, which, together with biological quality control
      mechanisms, helps proteins remain soluble and therefore functional in nature.

PMID- 21876183
TI  - Photoelectron spectroscopic and computational studies of the Pt@Pb10-1 and
      Pt@Pb121-/2- anions.
AB  - A combination of anion photoelectron spectroscopy and density functional theory
      calculations has elucidated the geometric and electronic structure of gas-phase
      endohedral Pt/Pb cage cluster anions. The anions, Pt@Pb10-1 and Pt@Pb121- were
      prepared from "preassembled" clusters generated from crystalline samples of
      [K(2,2,2-crypt)]2[Pt@Pb12] that were brought into the gas phase using a unique
      infrared desorption/photoemission anion source. The use of crystalline [K(2,2,2
      crypt)]2[Pt@Pb12] also provided access to K[Pt@Pb(n)](-) anions in the gas phase
      (i.e., the K+ salts of the Pt@Pb(n)2- anions). Anion photoelectron spectra of
      Pt@Pb10-1, Pt@Pb121-, and K[Pt@Pb12]1- are presented. Extensive density
      functional theory calculations on Pt@Pb103-/2-/1-/0 and Pt@Pb122-/1- provided
      candidate structures and anion photoelectron spectra for Pt@Pb10-1 and Pt@Pb121-.
      Together, the calculated and measured photoelectron spectra show that Pt@Pb10-1
      and Pt@Pb122-/1- endohedral complexes maintain their respective D(4d) and
      slightly distorted I(h) symmetries in the gas phase even for the charge states
      with open shell character. Aside from the fullerenes, the Pt@Pb122- endohedral
      complex is the only bare cluster that has been structurally characterized in the
      solid state, solution, and the gas phase.

PMID- 21876185
TI  - Reiterative Recombination for the in vivo assembly of libraries of multigene
      pathways.
AB  - The increasing sophistication of synthetic biology is creating a demand for
      robust, broadly accessible methodology for constructing multigene pathways inside
      of the cell. Due to the difficulty of rationally designing pathways that function
      as desired in vivo, there is a further need to assemble libraries of pathways in
      parallel, in order to facilitate the combinatorial optimization of performance.
      While some in vitro DNA assembly methods can theoretically make libraries of
      pathways, these techniques are resource intensive and inherently require
      additional techniques to move the DNA back into cells. All previously reported in
      vivo assembly techniques have been low yielding, generating only tens to hundreds
      of constructs at a time. Here, we develop "Reiterative Recombination," a robust
      method for building multigene pathways directly in the yeast chromosome. Due to
      its use of endonuclease-induced homologous recombination in conjunction with
      recyclable markers, Reiterative Recombination provides a highly efficient,
      technically simple strategy for sequentially assembling an indefinite number of
      DNA constructs at a defined locus. In this work, we describe the design and
      construction of the first Reiterative Recombination system in Saccharomyces
      cerevisiae, and we show that it can be used to assemble multigene constructs. We
      further demonstrate that Reiterative Recombination can construct large mock
      libraries of at least 10(4) biosynthetic pathways. We anticipate that our
      system's simplicity and high efficiency will make it a broadly accessible
      technology for pathway construction and render it a valuable tool for optimizing
      pathways in vivo.

PMID- 21876186
TI  - Wave drag on floating bodies.
AB  - We measure the deceleration of liquid nitrogen drops floating at the surface of a
      liquid bath. On water, the friction force is found to be about 10 to 100 times
      larger than on a solid substrate, which is shown to arise from wave resistance.
      We investigate the influence of the bath viscosity and show that the dissipation
      decreases as the viscosity is increased, owing to wave damping. The measured
      resistance is well predicted by a model imposing a vertical force (i.e., the drop
      weight) on a finite area, as long as the wake can be considered stationary.

PMID- 21876184
TI  - The former annotated human pseudogene dihydrofolate reductase-like 1 (DHFRL1) is
      expressed and functional.
AB  - Human dihydrofolate reductase (DHFR) was previously thought to be the only enzyme
      capable of the reduction of dihydrofolate to tetrahydrofolate; an essential
      reaction necessary to ensure a continuous supply of biologically active folate.
      DHFR has been studied extensively from a number of perspectives because of its
      role in health and disease. Although the presence of a number of intronless DHFR
      pseudogenes has been known since the 1980s, it was assumed that none of these
      were expressed or functional. We show that humans do have a second dihydrofolate
      reductase enzyme encoded by the former pseudogene DHFRP4, located on chromosome
      3. We demonstrate that the DHFRP4, or dihydrofolate reductase-like 1 (DHFRL1),
      gene is expressed and shares some commonalities with DHFR. Recombinant DHFRL1 can
      complement a DHFR-negative phenotype in bacterial and mammalian cells but has a
      lower specific activity than DHFR. The K(m) for NADPH is similar for both enzymes
      but DHFRL1 has a higher K(m) for dihydrofolate when compared to DHFR. The need
      for a second reductase with lowered affinity for its substrate may fulfill a
      specific cellular requirement. The localization of DHFRL1 to the mitochondria, as
      demonstrated by confocal microscopy, indicates that mitochondrial dihydrofolate
      reductase activity may be optimal with a lowered affinity for dihydrofolate. We
      also found that DHFRL1 is capable of the same translational autoregulation as
      DHFR by binding to its own mRNA; with each enzyme also capable of replacing the
      other. The identification of DHFRL1 will have implications for previous research
      involving DHFR.

PMID- 21876187
TI  - Quantum heat engine power can be increased by noise-induced coherence.
AB  - Laser and photocell quantum heat engines (QHEs) are powered by thermal light and
      governed by the laws of quantum thermodynamics. To appreciate the deep connection
      between quantum mechanics and thermodynamics we need only recall that in 1901
      Planck introduced the quantum of action to calculate the entropy of thermal
      light, and in 1905 Einstein's studies of the entropy of thermal light led him to
      introduce the photon. Then in 1917, he discovered stimulated emission by using
      detailed balance arguments. Half a century later, Scovil and Schulz-DuBois
      applied detailed balance ideas to show that maser photons were produced with
      Carnot quantum efficiency (see Fig. 1A). Furthermore, Shockley and Quiesser
      invoked detailed balance to obtain the efficiency of a photocell illuminated by
      "hot" thermal light (see Fig. 2A). To understand this detailed balance limit, we
      note that in the QHE, the incident light excites electrons, which can then
      deliver useful work to a load. However, the efficiency is limited by radiative
      recombination in which the excited electrons are returned to the ground state.
      But it has been proven that radiatively induced quantum coherence can break
      detailed balance and yield lasing without inversion. Here we show that noise
      induced coherence enables us to break detailed balance and get more power out of
      a laser or photocell QHE. Surprisingly, this coherence can be induced by the same
      noisy (thermal) emission and absorption processes that drive the QHE (see Fig.
      3A). Furthermore, this noise-induced coherence can be robust against
      environmental decoherence.Fig. 1.(A) Schematic of a laser pumped by hot photons
      at temperature T(h) (energy source, blue) and by cold photons at temperature T(c)
      (entropy sink, red). The laser emits photons (green) such that at threshold the
      laser photon energy and pump photon energy is related by Carnot efficiency (4).
      (B) Schematic of atoms inside the cavity. Lower level b is coupled to the excited
      states a and beta. The laser power is governed by the average number of hot and
      cold thermal photons, and . (C) Same as B but lower b level is replaced by two
      states b(1) and b(2), which can double the power when there is coherence between
      the levels.Fig. 2.(A) Schematic of a photocell consisting of quantum dots
      sandwiched between p and n doped semiconductors. Open circuit voltage and solar
      photon energy hnu(h) are related by the Carnot efficiency factor where T(c) is
      the ambient and T(h) is the solar temperature. (B) Schematic of a quantum dot
      solar cell in which state b is coupled to a via, e.g., solar radiation and
      coupled to the valence band reservoir state beta via optical phonons. The
      electrons in conduction band reservoir state alpha pass to state beta via an
      external circuit, which contains the load. (C) Same as B but lower level b is
      replaced by two states b(1) and b(2), and when coherently prepared can double the
      output power.Fig. 3.(A) Photocell current j = Gammarho(alphaalpha) (laser photon
      flux P(l)/h(nu(l))) (in arbitrary units) generated by the photovoltaic cell QHE
      (laser QHE) of Fig. 1C (Fig. 2C) as a function of maximum work (in electron
      volts) done by electron (laser photon) E(alpha) - E(beta) + kT(c)
      log(rho(alphaalpha)/rho(betabeta)) with full (red line), partial (brown line),
      and no quantum interference (blue line). (B) Power of a photocell of Fig. 2C as a
      function of voltage for different decoherence rates , 100gamma(1c). Upper curve
      indicates power acquired from the sun.

PMID- 21876189
TI  - Reaction chemistry ABC-style.

PMID- 21876188
TI  - Identification of a de novo thymidylate biosynthesis pathway in mammalian
      mitochondria.
AB  - The de novo and salvage dTTP pathways are essential for maintaining cellular dTTP
      pools to ensure the faithful replication of both mitochondrial and nuclear DNA.
      Disregulation of dTTP pools results in mitochondrial dysfunction and nuclear
      genome instability due to an increase in uracil misincorporation. In this study,
      we identified a de novo dTMP synthesis pathway in mammalian mitochondria.
      Mitochondria purified from wild-type Chinese hamster ovary (CHO) cells and HepG2
      cells converted dUMP to dTMP in the presence of NADPH and serine, through the
      activities of mitochondrial serine hydroxymethyltransferase (SHMT2), thymidylate
      synthase (TYMS), and a novel human mitochondrial dihydrofolate reductase (DHFR)
      previously thought to be a pseudogene known as dihydrofolate reductase-like
      protein 1 (DHFRL1). Human DHFRL1, SHMT2, and TYMS were localized to mitochondrial
      matrix and inner membrane, confirming the presence of this pathway in
      mitochondria. Knockdown of DHFRL1 using siRNA eliminated DHFR activity in
      mitochondria. DHFRL1 expression in CHO glyC, a previously uncharacterized mutant
      glycine auxotrophic cell line, rescued the glycine auxotrophy. De novo
      thymidylate synthesis activity was diminished in mitochondria isolated from glyA
      CHO cells that lack SHMT2 activity, as well as mitochondria isolated from wild
      type CHO cells treated with methotrexate, a DHFR inhibitor. De novo thymidylate
      synthesis in mitochondria prevents uracil accumulation in mitochondrial DNA
      (mtDNA), as uracil levels in mtDNA isolated from glyA CHO cells was 40% higher
      than observed in mtDNA isolated from wild-type CHO cells. These data indicate
      that unlike other nucleotides, de novo dTMP synthesis occurs within mitochondria
      and is essential for mtDNA integrity.

PMID- 21876190
TI  - Prediction of hepatocellular carcinoma development by plasma ADAMTS13 in chronic
      hepatitis B and C.
AB  - BACKGROUND: Chronic liver injury evokes a wound healing response, promoting
      fibrosis and finally hepatocellular carcinoma (HCC), in which hepatic stellate
      cells play an important role. Although a blood marker of hepatic stellate cells
      is not known, those cells importantly contribute to the regulation of plasma a
      disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13
      (ADAMTS13) activity, a defect of which causes thrombotic thrombocytopenic
      purpura. METHODS: Plasma ADAMTS13 was evaluated in chronic hepatitis B or C
      patients with or without HCC. RESULTS: Plasma ADAMTS13 activity significantly
      correlated with serum aspartate aminotransferase and alanine aminotransferase,
      liver stiffness value, and aspartate aminotransferase-to-platelet ratio index,
      irrespective of the presence of HCC, suggesting that it may reflect
      hepatocellular damage and subsequent wound healing and fibrosis as a result of
      hepatic stellate cell action. During the three-year follow-up period for patients
      without HCC, it developed in 10 among 81 patients. Plasma ADAMTS13 activity was
      significantly higher in patients with HCC development than in those without and
      was a significant risk for HCC development by univariate and multivariate
      analyses. Furthermore, during the one-year follow-up period for patients with HCC
      treated with radiofrequency ablation, HCC recurred in 55 among 107 patients.
      Plasma ADAMTS13 activity or antigen level was significantly higher in patients
      with HCC recurrence than in those without and was retained as a significant risk
      for HCC recurrence by multivariate analysis. CONCLUSIONS: Higher plasma ADAMTS13
      activity and antigen level was a risk of HCC development in chronic liver
      disease. IMPACT: Plasma ADAMTS13 as a potential marker of hepatic stellate cells
      may be useful in the prediction of hepatocarcinogenesis.

PMID- 21876191
TI  - Cancer fatalism: deterring early presentation and increasing social inequalities?
AB  - BACKGROUND: Fatalistic beliefs about cancer have been implicated in low uptake of
      screening and delay in presentation particularly in low socioeconomic status
      (SES) groups, but no studies have systematically evaluated interrelationships
      between SES, fatalism, and early detection behaviors. We explored whether (i)
      fatalism is associated with negative attitudes toward early detection, (ii) lower
      SES groups are more fatalistic, and (iii) SES differences in fatalism partly
      explain SES differences in attitudes toward early detection. METHODS: In a
      population-representative sample of adults in Britain using computer-based
      interviews in the home setting, respondents (N = 2,018) answered two questions to
      index fatalism (expectations of cancer survival and cure) and two items on early
      detection attitudes (the perceived value of early detection and fear of symptom
      reporting). SES was indexed with a social grade classification. RESULTS: Fatalism
      was associated with being less positive about early detection (beta = -0.40, P <
      0.001) and more fearful about seeking help for a suspicious symptom (beta = 0.24,
      P < 0.001). Lower SES groups were more fatalistic (beta = -0.21, P < 0.001). Path
      analyses suggest that SES differences in fatalism might explain SES differences
      in attitudes about early detection. CONCLUSIONS: In this population sample, SES
      differences in fatalism partly explained SES differences in the perceived value
      of early detection and fear of symptom presentation. IMPACT: Fatalistic beliefs
      about cancer should be targeted to promote early presentation of cancer and this
      may be particularly important for lower SES groups.

PMID- 21876192
TI  - Teaching NeuroImages: benediction sign as a result of cervical astrocytoma with
      syringomyelia.

PMID- 21876193
TI  - Teaching NeuroImages: myelopathy due to B12 deficiency in long-term colchicine
      treatment and nitrous oxide misuse.

PMID- 21876194
TI  - Do neurologists make a difference in Parkinson disease care?

PMID- 21876197
TI  - Rapid emergence of temporal and pulvinar lesions in MELAS mimicking Creutzfeldt
      Jakob disease.

PMID- 21876198
TI  - Neurology Journal Club: a new subsection.
AB  - The term "journal club" traditionally refers to a gathering of physicians for the
      critical review of current medical literature and discussion regarding the
      clinical application of the results. Since the formation of the first documented
      journal club over 130 years ago, the organization and purpose of this academic
      tool has gone through many changes. Despite the advent of "virtual" online
      journal clubs, most academic departments still employ a physical meeting between
      trainees and the faculty. The Neurology(r) Journal Club is a new subsection of
      the Resident & Fellow Section with the goal of enhancing the traditional journal
      club experience by publishing examples of structured critical appraisals of
      medical literature. The Journal Club critiques, written by neurology residents
      and fellows with faculty supervision, will examine each article for key features
      of hypothesis and design, methods, results, and interpretation.

PMID- 21876199
TI  - Journal Club: estimating risk for developing epilepsy: a population-based study
      in Rochester, Minnesota.

PMID- 21876200
TI  - Acute and preventive pharmacologic treatment of cluster headache.

PMID- 21876201
TI  - Fulminant encephalopathy with basal ganglia hyperintensities in HIV-infected drug
      users.

PMID- 21876202
TI  - Categorizing biases in high-confidence high-throughput protein-protein
      interaction data sets.
AB  - We characterized and evaluated the functional attributes of three yeast high
      confidence protein-protein interaction data sets derived from affinity
      purification/mass spectrometry, protein-fragment complementation assay, and yeast
      two-hybrid experiments. The interacting proteins retrieved from these data sets
      formed distinct, partially overlapping sets with different protein-protein
      interaction characteristics. These differences were primarily a function of the
      deployed experimental technologies used to recover these interactions. This
      affected the total coverage of interactions and was especially evident in the
      recovery of interactions among different functional classes of proteins. We found
      that the interaction data obtained by the yeast two-hybrid method was the least
      biased toward any particular functional characterization. In contrast,
      interacting proteins in the affinity purification/mass spectrometry and protein
      fragment complementation assay data sets were over- and under-represented among
      distinct and different functional categories. We delineated how these differences
      affected protein complex organization in the network of interactions, in
      particular for strongly interacting complexes (e.g. RNA and protein synthesis)
      versus weak and transient interacting complexes (e.g. protein transport). We
      quantified methodological differences in detecting protein interactions from
      larger protein complexes, in the correlation of protein abundance among
      interacting proteins, and in their connectivity of essential proteins. In the
      latter case, we showed that minimizing inherent methodology biases removed many
      of the ambiguous conclusions about protein essentiality and protein connectivity.
      We used these findings to rationalize how biological insights obtained by
      analyzing data sets originating from different sources sometimes do not agree or
      may even contradict each other. An important corollary of this work was that
      discrepancies in biological insights did not necessarily imply that one detection
      methodology was better or worse, but rather that, to a large extent, the insights
      reflected the methodological biases themselves. Consequently, interpreting the
      protein interaction data within their experimental or cellular context provided
      the best avenue for overcoming biases and inferring biological knowledge.

PMID- 21876203
TI  - A tool for biomarker discovery in the urinary proteome: a manually curated human
      and animal urine protein biomarker database.
AB  - Urine is an important source of biomarkers. A single proteomics assay can
      identify hundreds of differentially expressed proteins between disease and
      control samples; however, the ability to select biomarker candidates with the
      most promise for further validation study remains difficult. A bioinformatics
      tool that allows accurate and convenient comparison of all of the existing
      related studies can markedly aid the development of this area. In this study, we
      constructed the Urinary Protein Biomarker (UPB) database to collect existing
      studies of urinary protein biomarkers from published literature. To ensure the
      quality of data collection, all literature was manually curated. The website
      (http://122.70.220.102/biomarker) allows users to browse the database by disease
      categories and search by protein IDs in bulk. Researchers can easily determine
      whether a biomarker candidate has already been identified by another group for
      the same disease or for other diseases, which allows for the confidence and
      disease specificity of their biomarker candidate to be evaluated. Additionally,
      the pathophysiological processes of the diseases can be studied using our
      database with the hypothesis that diseases that share biomarkers may have the
      same pathophysiological processes. Because of the natural relationship between
      urinary proteins and the urinary system, this database may be especially suitable
      for studying the pathogenesis of urological diseases. Currently, the database
      contains 553 and 275 records compiled from 174 and 31 publications of human and
      animal studies, respectively. We found that biomarkers identified by different
      proteomic methods had a poor overlap with each other. The differences between
      sample preparation and separation methods, mass spectrometers, and data analysis
      algorithms may be influencing factors. Biomarkers identified from animal models
      also overlapped poorly with those from human samples, but the overlap rate was
      not lower than that of human proteomics studies. Therefore, it is not clear how
      well the animal models mimic human diseases.

PMID- 21876204
TI  - iProphet: multi-level integrative analysis of shotgun proteomic data improves
      peptide and protein identification rates and error estimates.
AB  - The combination of tandem mass spectrometry and sequence database searching is
      the method of choice for the identification of peptides and the mapping of
      proteomes. Over the last several years, the volume of data generated in proteomic
      studies has increased dramatically, which challenges the computational approaches
      previously developed for these data. Furthermore, a multitude of search engines
      have been developed that identify different, overlapping subsets of the sample
      peptides from a particular set of tandem mass spectrometry spectra. We present
      iProphet, the new addition to the widely used open-source suite of proteomic data
      analysis tools Trans-Proteomics Pipeline. Applied in tandem with PeptideProphet,
      it provides more accurate representation of the multilevel nature of shotgun
      proteomic data. iProphet combines the evidence from multiple identifications of
      the same peptide sequences across different spectra, experiments, precursor ion
      charge states, and modified states. It also allows accurate and effective
      integration of the results from multiple database search engines applied to the
      same data. The use of iProphet in the Trans-Proteomics Pipeline increases the
      number of correctly identified peptides at a constant false discovery rate as
      compared with both PeptideProphet and another state-of-the-art tool Percolator.
      As the main outcome, iProphet permits the calculation of accurate posterior
      probabilities and false discovery rate estimates at the level of sequence
      identical peptide identifications, which in turn leads to more accurate
      probability estimates at the protein level. Fully integrated with the Trans
      Proteomics Pipeline, it supports all commonly used MS instruments, search
      engines, and computer platforms. The performance of iProphet is demonstrated on
      two publicly available data sets: data from a human whole cell lysate proteome
      profiling experiment representative of typical proteomic data sets, and from a
      set of Streptococcus pyogenes experiments more representative of organism
      specific composite data sets.

PMID- 21876205
TI  - A face in the crowd: recognizing peptides through database search.
AB  - Peptide identification via tandem mass spectrometry sequence database searching
      is a key method in the array of tools available to the proteomics researcher. The
      ability to rapidly and sensitively acquire tandem mass spectrometry data and
      perform peptide and protein identifications has become a commonly used proteomics
      analysis technique because of advances in both instrumentation and software.
      Although many different tandem mass spectrometry database search tools are
      currently available from both academic and commercial sources, these algorithms
      share similar core elements while maintaining distinctive features. This review
      revisits the mechanism of sequence database searching and discusses how various
      parameter settings impact the underlying search.

PMID- 21876206
TI  - Realizing empowerment in difficult diabetes care: a guided self-determination
      intervention.
AB  - Although health professionals advocate empowerment in patient care, they often
      fail to realize it in practice. Through grounded theories we previously explained
      why barriers to empowerment were seldom overcome in diabetes care. Zoffmann used
      these theories as a basis for developing a decision-making and problem-solving
      method called guided self-determination (GSD). To realize empowerment, health
      professionals need detailed knowledge of the barriers, their own roles in these
      barriers, ways to overcome them, and recognizable evidence of having succeeded.
      Through theory-driven, qualitative evaluation, the previously developed grounded
      theories helped us recognize changes consistent with empowerment in dyads of
      nurses and patients with poorly controlled type 1 diabetes. By completing GSD
      reflection, patients remarkably improved their ability to identify, express, and
      share unique and unexpected difficulties related to living with diabetes. As
      signs of empowerment, patients and health professionals accomplished shared
      decision making, resolved life-disease conflicts, and established meaningful and
      effective relationships.

PMID- 21876207
TI  - The relationship between symbolic interactionism and interpretive description.
AB  - In this article I explore the relationship between symbolic interactionist theory
      and interpretive description methodology. The two are highly compatible, making
      symbolic interactionism an excellent theoretical framework for interpretive
      description studies. The pragmatism underlying interpretive description supports
      locating the methodology within this cross-disciplinary theory to make it more
      attractive to nonnursing researchers and expand its potential to address practice
      problems across the applied disciplines. The theory and method are so compatible
      that symbolic interactionism appears to be part of interpretive description's
      epistemological foundations. Interpretive description's theoretical roots have,
      to date, been identified only very generally in interpretivism and the philosophy
      of nursing. A more detailed examination of its symbolic interactionist heritage
      furthers the contextualization or forestructuring of the methodology to meet one
      of its own requirements for credibility.

PMID- 21876208
TI  - Passing through: meanings of survivorship and support among Filipinas with breast
      cancer.
AB  - Breast cancer among Filipinas in the United States is a major but largely
      neglected cancer disparity. In 2004, a community- university partnership resulted
      in the first Filipina breast cancer support group in the San Francisco Bay Area.
      Building on this partnership, we explored the social and cultural contexts of
      Filipinas' experiences with breast cancer to inform development of culturally
      appropriate and sustainable support services and outreach. We utilized multiple
      qualitative methods (participant observation, individual and small group in-depth
      qualitative interviews) to identify meanings of survivorship and support.
      Interviews and observations revealed the influences of social context and
      immigration experiences on women's understandings of cancer, what "surviving"
      cancer means, and what it means to take care of someone with breast cancer (or be
      taken care of). Our findings highlight the importance of a transnational
      perspective for the study of immigrant women's experiences of cancer and
      survivorship.

PMID- 21876209
TI  - Unsolicited written narratives as a methodological genre in terminal illness:
      challenges and limitations.
AB  - Stories about illness have proven invaluable in helping health professionals
      understand illness experiences. Such narratives have traditionally been solicited
      by researchers through interviews and the collection of personal writings,
      including diaries. These approaches are, however, researcher driven; the impetus
      for the creation of the story comes from the researcher and not the narrator. In
      recent years there has been exponential growth in illness narratives created by
      individuals, of their own volition, and made available for others to read in
      print or as Internet accounts. We sought to determine whether it was possible to
      identify such material for use as research data to explore the subject of living
      with the terminal illness amyotrophic lateral sclerosis/motor neuron disease--the
      contention being that these accounts are narrator driven and therefore focus on
      issues of greatest importance to the affected person. We encountered and sought
      to overcome a number of methodological and ethical challenges, which is our focus
      here.

PMID- 21876212
TI  - Evaluation of a bayesian coalescent method of species delimitation.
AB  - A Bayesian coalescent-based method has recently been proposed to delimit species
      using multilocus genetic sequence data. Posterior probabilities of different
      species delimitation models are calculated using reversible-jump Markov chain
      Monte Carlo algorithms. The method accounts for species phylogenies and
      coalescent events in both extant and extinct species and accommodates lineage
      sorting and uncertainties in the gene trees. Although the method is theoretically
      appealing, its utility in practical data analysis is yet to be rigorously
      examined. In particular, the analysis may be sensitive to priors on ancestral
      population sizes and on species divergence times and to gene flow between
      species. Here we conduct a computer simulation to evaluate the statistical
      performance of the method, such as the false negatives (the error of lumping
      multiple species into one) and false positives (the error of splitting one
      species into several). We found that the correct species model was inferred with
      high posterior probability with only one or two loci when 5 or 10 sequences were
      sampled from each population, or with 50 loci when only one sequence was sampled.
      We also simulated data allowing migration under a two-species model, a mainland
      island model and a stepping-stone model to assess the impact of gene flow
      (hybridization or introgression). The behavior of the method was diametrically
      different depending on the migration rate. Low rates at < 0.1 migrants per
      generation had virtually no effect, so that the method, while assuming no
      hybridization between species, identified distinct species despite small amounts
      of gene flow. This behavior appears to be consistent with biologists' practice.
      In contrast, higher migration rates at >= 10 migrants per generation caused the
      method to infer one species. At intermediate levels of migration, the method is
      indecisive. Our results suggest that Bayesian analysis under the multispecies
      coalescent model may provide important insights into population divergences, and
      may be useful for generating hypotheses of species delimitation, to be assessed
      with independent information from anatomical, behavioral, and ecological data.

PMID- 21876211
TI  - The antiepileptic drug valproic acid and other medium-chain fatty acids acutely
      reduce phosphoinositide levels independently of inositol in Dictyostelium.
AB  - Valproic acid (VPA) is the most widely prescribed epilepsy treatment worldwide,
      but its mechanism of action remains unclear. Our previous work identified a
      previously unknown effect of VPA in reducing phosphoinositide production in the
      simple model Dictyostelium followed by the transfer of data to a mammalian
      synaptic release model. In our current study, we show that the reduction in
      phosphoinositide [PtdInsP (also known as PIP) and PtdInsP(2) (also known as
      PIP(2))] production caused by VPA is acute and dose dependent, and that this
      effect occurs independently of phosphatidylinositol 3-kinase (PI3K) activity,
      inositol recycling and inositol synthesis. In characterising the structural
      requirements for this effect, we also identify a family of medium-chain fatty
      acids that show increased efficacy compared with VPA. Within the group of active
      compounds is a little-studied group previously associated with seizure control,
      and analysis of two of these compounds (nonanoic acid and 4-methyloctanoic acid)
      shows around a threefold enhanced potency compared with VPA for protection in an
      in vitro acute rat seizure model. Together, our data show that VPA and a newly
      identified group of medium-chain fatty acids reduce phosphoinositide levels
      independently of inositol regulation, and suggest the reinvestigation of these
      compounds as treatments for epilepsy.

PMID- 21876213
TI  - Hypertension is common among HIV-infected persons, but not associated with HAART.
AB  - BACKGROUND: With improved survival after the introduction of highly active
      antiretroviral therapy (HAART), non-AIDS-related morbidity and mortality have
      come to the forefront in the management of HIV patients. HAART has been linked to
      the development of several risk factors for cardiovascular disease including
      insulin resistance and hyperlipidemia, but its influence on hypertension requires
      further study. METHODS: We performed a cross-sectional study of HIV-infected
      persons at two large HIV clinics to evaluate the prevalence and factors
      associated with hypertension. Hypertension was defined by at least two blood
      pressure measurements >140/90 mmHg or the use of an antihypertensive medication.
      Statistical analyses included multivariate logistic regression models. RESULTS:
      We studied 707 HIV-infected adults with a median age of 41 years (IQR 36-46), 92%
      were male, 49% were Caucasian, and 72% were receiving HAART. The overall
      prevalence of hypertension was 31% and was similar among those receiving and not
      receiving HAART (32% vs. 29%, p = 0.47). Factors associated with hypertension in
      the multivariate model included increasing age, longer duration of HIV, higher
      body mass index, and diabetes, with a trend for African American ethnicity.
      CONCLUSIONS: Hypertension is common among HIV-infected persons and is associated
      with established risk factors, but not with HAART use. Given the high prevalence
      of hypertension and its association with duration of HIV infection, other factors
      such as virally-mediated endothelial changes or immune activation may play a
      role. Further investigations are needed.

PMID- 21876214
TI  - Abandonment of antiretroviral therapy among HIV-positive patients attended at the
      reference center for HIV/AIDS in Vitoria, Brazil.
AB  - This study evaluates the risk factors for the abandonment of antiretroviral
      therapy (ART) among patients receiving care in an AIDS clinic in Vitoria, Brazil.
      We conducted a case-control study of patients with AIDS attending a reference
      center for sexually transmitted disease (STD)/AIDS. A total of 62 patients, who
      abandoned therapy in 2008, and 188 HIV-infected patients answered an interview
      including demographic, social, and clinical characteristics. Risk factors
      associated with abandon in univariate analysis were entered into logistic
      regression models. A total of 250 patients were included in the study. Groups
      were similar regarding age, gender, and monthly income. In the final multivariate
      model, illicit drug use (adjusted odds ratio [AOR], 2.3; 95% confidence interval
      [CI], 1.03-5.07), previous abandon of medication (AOR 38.6; 95% CI 10.49-142.25),
      last CD4 count <200 cells/mm(3) (AOR 1.5; 95% CI 1.03-2.10), and viral load
      higher than 1000 copies/mL (AOR 2.0 (95% CI 1.34-3.09) were independent
      predictors of abandonment of ART. In addition to the clinical indicators,
      behavioral factors remained important throughout the multivariate analysis in our
      study.

PMID- 21876215
TI  - Moving from viral suppression to comprehensive patient-centered care: the high
      prevalence of comorbid conditions and health risk factors in HIV-1-infected
      patients in Australia.
AB  - HIV clinicians today need to move from focusing on viral suppression to a chronic
      disease model in which comorbid conditions and risk factors are comprehensively
      identified and addressed to reduce rates of serious non-AIDS-related morbidity
      and mortality. This study aimed to determine the prevalence of comorbid
      conditions in an Australian HIV-positive population. Of 180 patients included,
      there was a median CD4 count of 0.520 cells/mm(3). The majority (88%) of patients
      were currently receiving highly active antiretroviral therapy (HAART). There were
      high rates of failure to attend clinical appointments (30%), current smoking
      (42%), hypertension (16%), and dyslipidemia (17%). Significant rates of dipstick
      positive proteinuria (16%) and elevated blood glucose (15%) were recorded. Risk
      factors were commonly not addressed by the treating clinician. There is an urgent
      need to systematize detection and management of high-prevalence comorbid
      conditions to prevent premature mortality associated with serious non-AIDS
      events.

PMID- 21876216
TI  - Prevalence of asymptomatic bacterial sexually transmitted infections in
      hospitalized HIV patients in Baltimore City.
AB  - Sexually transmitted infections (STIs) are known to promote the transmission of
      HIV. Diagnosing these infections can identify patients engaging in high-risk
      behaviors and provides an opportunity for intervention and education. The Centers
      for Disease Control and Prevention (CDC) recommends STI screening as part of
      routine HIV care. Ninety HIV-infected inpatients admitted to the University of
      Maryland Hospital were screened for gonorrhea, chlamydia, and syphilis. None of
      the nucleic acid amplification probes were positive for gonorrhea, and 1 was
      positive for chlamydia. A total of 8 rapid plasma reagin (RPR) tests were
      positive, 2 of which are believed to be associated with new infection or
      treatment failure. Rapid plasma reagin positivity was found to be associated with
      men who have sex with men (MSM), low CD4 count, and high HIV viral load. Routine
      inpatient screening for asymptomatic STIs in HIV-infected patients may be
      beneficial, particularly patients not engaged in routine outpatient care.

PMID- 21876217
TI  - How the Illicit Drug Economy Contributes to HIV Risk in St Vincent and the
      Grenadines.
AB  - St Vincent and the Grenadines (SVG) is the largest marijuana producer in the
      Eastern Caribbean. As the European Union has phased out preferred access for its
      banana crop, marijuana has become one of the main sources of income and a safety
      net for many young men, in particular. HIV is a problem for youth in SVG where
      60% of the population and 50% of cumulative AIDS cases are among individuals
      under 30 years of age. To explore the relationship between the economic context
      and HIV, we used rapid appraisal methods including field observations,
      interviews, and focus groups with 43 key informants. We found that the marijuana
      related economy has contributed to social conditions favoring HIV transmission
      among young people in several interrelated ways. A lively youth culture exists
      which includes frequent parties, heavy drinking, sex with multiple partners, and
      the desire to be seen with the best material goods. Men with access to money are
      able to attract younger partners for parties and sex. Condoms are infrequently
      used. We conclude that reducing HIV risk will require structural interventions to
      reduce discrimination and increase economic opportunity.

PMID- 21876218
TI  - Functional characterization of alpha-class glutathione s-transferases from the
      Turkey (meleagris gallopavo).
AB  - Six Alpha-class glutathione S-transferase (GST) subunits were cloned from
      domestic turkey livers, which are one of the most susceptible animals known to
      the carcinogenic mycotoxin aflatoxin B1. In most animals, GST dysfunction is a
      risk factor for susceptibility toward AFB1, and we have shown that turkeys lack
      GSTs with affinity toward the carcinogenic intermediate exo-aflatoxin B(1)-8-9
      epoxide (AFBO). Conversely, mice are resistant to AFB1 carcinogenesis, due to
      high constitutive expression of mGSTA3 that has high affinity toward AFBO. When
      expressed in Escherichia coli, all six tGSTA subunits possessed conjugating
      activities toward substrates 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4
      nitrobenzene (DCNB), ethacrynic acid (ECA), and cumene hydroperoxide (CHP) with
      tGSTA1.2 appearing most active. Interestingly, tGSTA1.1, which lacks one of the
      four Alpha-class signature motifs, possessed enzymatic activities toward all
      substrates. All had comparable activities toward AFBO conjugation, an activity
      absent in turkey liver cytosols. E. coli-expressed mGSTA3 conjugated AFBO with
      more than 3-fold greater activity than that of tGSTAs and had higher activity
      toward GST prototype substrates. Mouse hepatic cytosols had approximately 900
      fold higher catalytic activity toward AFBO compared with those from turkey. There
      was no apparent amino acid profile in tGSTAs that might correspond to specificity
      toward AFBO, although tGSTA1.2, which had slightly higher AFBO-trapping ability,
      shared Tyr108 with mGSTA3, a residue postulated to be critical for AFBO trapping
      activity in mammalian systems. The observation that recombinant tGSTAs detoxify
      AFBO, whereas their hepatic forms do not, implies that the hepatic forms of these
      enzymes are silenced by one or more regulatory mechanisms.

PMID- 21876219
TI  - Comparison of the effects of rapid maxillary expansion caused by treatment with
      either a memory screw or a Hyrax screw on the dentofacial structures--transversal
      effects.
AB  - The aim of the present study was to investigate and compare the effects of
      conventional Hyrax screw treatment and memory screw treatment on skeletal and
      dentoalveolar structures. Thirty-two patients with maxillary transversal
      deficiency were divided into two groups. The memory-screw group included 17
      patients (nine females and eight males), while the Hyrax-screw group comprised 15
      patients (eight females and seven males). Mean ages of the subjects in the memory
      screw and Hyrax-screw groups were 13.00 +/- 1.29 and 12.58 +/- 1.50 years,
      respectively. Plaster models and postero-anterior cephalograms were taken from
      the patients at the beginning of the treatment (T1) and at the end of expansion
      (T2) and retention periods (T3). The mean expansion period was 7.76 +/- 1.04 days
      in the memory-screw group and 35.46 +/- 9.39 days in the Hyrax-screw group.
      'Shapiro-Wilk Normality test' was used to determine whether the investigated
      parameters were homogeneous or not. To determine the treatment changes within the
      group, 'paired t-test' and 'Wilcoxon signed-ranks test' were applied to the
      homogeneous and non-homogeneous parameters, respectively. Comparison between the
      groups was carried out using 'Student's t-test' for homogeneous parameters and
      'Mann-Whitney U-test' for the rest. Rapid maxillary expansion was carried out
      successfully in both the groups. However, the use of memory screw may be
      advantageous because it shortens the maxillary expansion period, provides
      additional expansion in the retention period, and generates light forces relative
      to the conventional Hyrax screw. 

PMID- 21876220
TI  - Conserved meiotic machinery in Glomus spp., a putatively ancient asexual fungal
      lineage.
AB  - Arbuscular mycorrhizal fungi (AMF) represent an ecologically important and
      evolutionarily intriguing group of symbionts of land plants, currently thought to
      have propagated clonally for over 500 Myr. AMF produce multinucleate spores and
      may exchange nuclei through anastomosis, but meiosis has never been observed in
      this group. A provocative alternative for their successful and long asexual
      evolutionary history is that these organisms may have cryptic sex, allowing them
      to recombine alleles and compensate for deleterious mutations. This is partly
      supported by reports of recombination among some of their natural populations. We
      explored this hypothesis by searching for some of the primary tools for a
      sustainable sexual cycle--the genes whose products are required for proper
      completion of meiotic recombination in yeast--in the genomes of four AMF and
      compared them with homologs of representative ascomycete, basidiomycete,
      chytridiomycete, and zygomycete fungi. Our investigation used molecular and
      bioinformatic tools to identify homologs of 51 meiotic genes, including seven
      meiosis-specific genes and other "core meiotic genes" conserved in the genomes of
      the AMF Glomus diaphanum (MUCL 43196), Glomus irregulare (DAOM-197198), Glomus
      clarum (DAOM 234281), and Glomus cerebriforme (DAOM 227022). Homology of AMF
      meiosis-specific genes was verified by phylogenetic analyses with representative
      fungi, animals (Mus, Hydra), and a choanoflagellate (Monosiga). Together, these
      results indicate that these supposedly ancient asexual fungi may be capable of
      undergoing a conventional meiosis; a hypothesis that is consistent with previous
      reports of recombination within and across some of their populations.

PMID- 21876222
TI  - [Genetic variability of the oxytocine receptor: an in silico study].
AB  - There is an ongoing extensive study on the polymorphisms of the oxytocine
      receptor (OXTR) gene and their relation to certain psychological traits and
      psychiatric disorders, however the results are contradictory. One of the sources
      of inconsistency could originate from the fact that the OXTR gene contains more
      than 270 SNPs (single nucleotide polymorphisms) without clarified molecular
      effect. GOALS: The aim of this study was an in silico analysis of sequence
      variations between the human and dog OXTR gene. RESULTS: Comparative analysis of
      the human and the dog OXTR amino acid sequence revealed that the most robust
      difference between the two proteins is a five amino acid containing fragment
      which is present in the human but absent in the dog receptor. In silico addition
      of this sequence to the dog receptor resulted in a dramatic change in the
      conformation of the intracellular region. CONCLUSION: In silico comparative
      analysis of OXTR gene variants among species and individuals might serve as an
      important cue for predicting the functional effects of genetic variants.

PMID- 21876221
TI  - [Clinical characteristics of cannabis-induced schizophrenia spectrum disorder].
AB  - Marijuana (cannabis) is the most commonly abused drug by adolescents and young
      adults and also by people with schizophrenia or other psychotic disorders. An
      increasing number of studies suggest that regular cannabis users can show
      psychotic episodes similar to schizophrenic disorders but it still unclear if
      cannabis induced psychotic disorder is a distinct entity requiring special
      therapy or regular cannabis use consequently leads to schizophrenia. Therefore,
      we retrospectively compared psychotic patients with and without cannabis use by
      clinical profile. Clinical data of 85 patients with schizophrenia spectrum
      disorder were analyzed retrospectively. Cannabis use was not reported by 43
      persons (Cnbs0 subgroup) and 42 patients used regularly cannabis during at least
      1 year (Cnbs1 subgroup). Clinical data were collected from electronic medical
      documentation of patients concerning anamnesis, family history, socio-demographic
      condition, symptoms and psychiatric state, acute and long-term therapies. Men
      were over-represented in the cannabis abuser group while mean age was lower among
      them compared to the Cnbs0 subgroup. Prevalence of suicidal attempts was
      increased in men without cannabis use. Patients without cannabis use spent more
      time in hospital and smoking was more frequent among them. Positive and negative
      symptoms and family history did not differ significantly between the two
      subgroups. Dosage, intensity and length of pharmacotherapy was different between
      the two subgroups. These results revealed that certain clinical aspects were
      different in case of cannabis-related schizophrenia spectrum disorder compared to
      schizophrenia.

PMID- 21876223
TI  - [Neurological symptoms in psychiatry].
AB  - Certain psychiatric diseases have biological pathomechanisms, and as a result
      they are accompanied by various neurological symptoms. Neurological examination
      is a simple method to assess these symptoms. Neurological signs come in two
      varieties; they are either of the hard or the soft type. Hard symptoms appear
      primarily in organic psychiatric disorders or as side effects of psychiatric
      therapy. They can also be encountered during neurological diseases of psychiatric
      patients. Their use in diagnostics and therapy is widely accepted. In contrast,
      soft neurological symptoms often stay unnoticed, even though they may contain
      important pieces of information. For this reason they will form the focus of our
      discussion. Soft neurological symptoms have been studied in different psychiatric
      disorder-groups. Up to now most attention has been devoted to schizophrenia. The
      study suggests that the soft symptoms are trait markers of schizophrenia.
      Furthermore they also signal disease activity and predict the outcome of the
      disease. Neurological symptoms are also important pointers for psychiatry.
      However, more systematic studies may increase the theoretical and practical
      implications of soft symptoms.

PMID- 21876224
TI  - [The optimal combination of ECT with pharmacotherapy].
AB  - The main indications for the electroconvulsive therapy (ECT) - psychotropic drug
      combination are pharmacotherapy-resistant, severe schizophrenic or affective
      psychoses. In such instances, a careful evaluation of the possible interactions
      between ECT and psychotropic drugs should precede the initiation of treatment in
      order to prevent adverse side effects. In this respect, the issues to be
      considered include the impact of concomittant pharmacotherapy on the seizure
      parameters of the ECT as well as the efficacy of the combined treatment relative
      to ECT or pharmacotherapy administered alone. This paper reviews the current
      literature on the use of benzodiazepines, mood stabilizers, antidepressants,
      antipsychotics together with ECT with the aim of providing recommendations for
      clinical practice.

PMID- 21876225
TI  - [Cytoskeletal alterations in Alzheimer's disease: the "skeleton" of therapeutic
      hope?].
AB  - Damage to and functional alteration of structures responsible for synaptic
      plasticity correlate with memory loss and cognitive decline in Alzheimer's
      disease. The results of recent research in the pathomechanism of Alzheimer's
      disease emphasize the significance of cytoskeletal changes. The changes in actin
      dynamics and its regulation by actin-binding proteins have been proven in
      Alzheimer's disease, which may have a key role in the conformation and alteration
      of synapses and dendritic spines. The most important proteins in the regulation
      of actin dynamics are ADF/cofilin, kinases and drebrin. In this review, we
      summarize the physiological functions and complex regulation of these
      cytoskeletal proteins and their alterations in Alzheimer's disease. Additionally,
      the effects of some psychopharmacons on the actin cytoskeleton and cytoskeletal
      changes induced by stress are also summarized.

PMID- 21876226
TI  - Running Max/Min Filters using 1+o(1) Comparisons per Sample.
AB  - A running max (or min) filter asks for the maximum or (minimum) elements within a
      fixed-length sliding window. The previous best deterministic algorithm (developed
      by Gil and Kimmel, and refined by Coltuc) can compute the 1D max filter using
      1.5+o(1) comparisons per sample in the worst case. The best known algorithm for
      independent and identically distributed input uses 1.25+o(1) expected comparisons
      per sample(by Gil and Kimmel). In this work, we show that the number of
      comparisons can be reduced to 1+o(1) comparisons per sample in the worst case. As
      a consequence of the new max/min filters, the opening (or closing) filter can
      also be computed using 1+o(1) comparisons per sample in the worst case, where the
      previous best work requires 1.5+o(1) comparisons per sample (by Gil and Kimmel);
      and computing the max and min filters simultaneously can be done in 2+o(1)
      comparisons per sample in the worst case, where the previous best work (by
      Lemire) requires 3 comparisons per sample. Our improvements over the previous
      work are asymptotic, that is, the number of comparisons is reduced only when the
      window size is large.

PMID- 21876227
TI  - A survey of visualization systems for network security.
AB  - Security Visualization is a very young term. It expresses the idea that common
      visualization techniques have been designed for use cases that are not supportive
      of security-related data, demanding novel techniques fine tuned for the purpose
      of thorough analysis. Significant amount of work has been published in this area,
      but little work has been done to study this emerging visualization discipline. We
      offer a comprehensive review of network security visualization and provide a
      taxonomy in the form of five use-case classes encompassing nearly all recent
      works in this area. We outline the incorporated visualization techniques and data
      sources and provide an informative table to display our findings. From the
      analysis of these systems, we examine issues and concerns regarding network
      security visualization and provide guidelines and directions for future
      researchers and visual system developers.

PMID- 21876228
TI  - Unraveling the complexity of basal-like breast cancer.

PMID- 21876229
TI  - Perspectives in clinical hemorheology and microcirculation: review of the
      conference of the German Society for Clinical Microcirculation and Hemorheology
      2010.

PMID- 21876230
TI  - Angiogenesis: the role of PDGF-BB on adipose-tissue derived stem cells (ASCs).
AB  - Recently, it was shown that mesenchymal stem cells (MSCs) are capable of
      differentiating into endothelial cells which highlights the potential role of
      MSCs in neovascularization. In the present study, we investigated the paracrine
      factors responsible for tube formation in human adipose-tissue derived stem cells
      (ASCs). Moreover, we analyzed ASC's migration towards PDGF-BB and altered levels
      of proteins involved in different pathways. Freshly isolated human adipose tissue
      derived stem cells were seeded onto wells coated with Matrigel and cultured in
      endothelial growth medium. Capillary-like tube formation was observed after 18
      hours culture. Tube formation was significantly reduced in the presence of
      antibodies against platelet-derived growth factor receptor beta (PDGF) or basic
      fibroblast growth factor (bFGF). Reverse phase proteomic assay (RPPA) was used to
      interrogate the expression of 139 phosphorylated or native proteins after
      incubation with PDGF-BB protein for 24 hours. The present data suggest, that
      freshly isolated ASCs contain a subpopuplation of stem cells that can form
      capillary like tubes which is dependent on PDGF and bFGF signaling pathway.
      Furthermore, Migration of human ASCs significantly increased in response to
      increased concentrations of PDGF-BB. In addition, incubation of ASCs with PDGF-BB
      altered phosphorylation of several transcription proteins that are widely
      expressed throughout the hematopoietic system, targeting genes that have been
      associated with proliferation, anti-apoptosis or differentiation.

PMID- 21876231
TI  - Angiopoietins differentially influence in vitro angiogenesis by endothelial cells
      of different origin.
AB  - Angiopoietins are important growth factors for vascular development and
      quiescence. They are promising targets for pro- or anti-angiogenic therapies in
      diverse pathologies, but the mechanisms of the ANGPT/TIE2 system are complex and
      not well understood. In the present study, the separate and combined effects of
      angiopoietin 1 and angiopoietin 2 were studied, using a recently developed in
      vitro angiogenesis model that allows both a quantitative and qualitative
      evaluation of the angiogenic cascade. This cell culture model was performed with
      microvascular endothelial cells (ECs) originating from different vascular beds,
      i.e. dermal ECs and cardiac ECs. In addition, the expression of the angiopoietins
      and the receptors, TIE1 and TIE2 was analyzed with RT-qPCR. This study revealed
      that the angiopoietins provoked a differential response in the two endothelial
      cultures. Both angiopoietin 1 as well as angiopoietin 2 elicited an angiogenic
      cascade in the dermal ECs but not in the cardiac ECs. In addition, the RT-qPCR
      data revealed marked differences in the endogenous expression pattern of these
      factors, indicating that the origin of endothelial cells might have an important
      impact on their angiogenic potential.

PMID- 21876232
TI  - Angiogenesis and healing with non-shrinking, fast degradeable PLGA/CaP scaffolds
      in critical-sized defects in the rabbit femur with or without osteogenically
      induced mesenchymal stem cells.
AB  - Cost effective and safely to apply tissue engineered constructs of big volume
      bone transplants for the reconstruction of critical sized defects (CSD) are still
      not available. Key problems with synthetic scaffold materials are shrinkage and
      fast degradation of the scaffolds, a lack of blood supply and nutrition in the
      central scaffold volume and the absent or the scarce development of bone tissue
      along the scaffold to bridge the bone defect. The use of composite scaffolds made
      of biopolymers like polylactidglycolid acid (PLGA) coated and loaded with calcium
      phosphates (CaP) revealed promising therapeutical options for the regeneration of
      critical sized bone defects. In this study interconnectively macroporous PLGA
      scaffolds loaded with microporous and coated with nanoporous calcium phosphates
      were either seeded in fixed bed bioreactors with allogenic osteogenically induced
      mesenchymal stem cells and implanted or implanted unseeded into critical sized
      femoral bone defects. As CSD a 12 mm long segment of the chinchilla femur was
      excised where the proximal and distal parts of the femur were fixed and
      stabilized by the use of an eight-hole linear reconstruction plate and secured
      with three bicortical screws (2.7 mm diameter) on every side of the osteotomy.
      Aim of the study was if we could find a way to load and coat PLGA scaffolds with
      CaP so that shrinkage of scaffolds could be avoided, which would favour
      angiogenesis, blood supply and nutrition in the construct and thus avoid central
      necroses regularly observed so far in transplants not vascularized and which
      would be inhabited by cells of he bone lineage forming new bone and healing the
      defect. Four weeks, at least, a notable shrinkage of the scaffolds was avoided
      and scaffolds were practically not degraded. Both scaffolds, loaded and loaded
      and coated, revealed blood vessels in all parts of the implants after 4 weeks.
      Only in scaffolds seeded with allogenic mesenchymal stem cells the development of
      bridging bone constructs between proximal and distal edges of the femur was
      observed after four weeks without further supplementation of growth factors. In
      case of the implantation of non-seeded scaffolds no obvious scaffold bound bone
      development could be shown.

PMID- 21876233
TI  - Influence of radiographic contrast media (iodixanol und iomeprol) on the
      morphology of human arterial and venous endothelial cells on extracellular matrix
      in vitro.
AB  - After intra-arterial administration of radiographic contrast media (RCM), a
      disorder of the downstream microcirculation both with regard to blood flow
      velocity in microvessels and to tissue oxygen partial pressure was described.
      Possible factors contributing to this microcirculatory disorder are increase in
      plasma viscosity, a formation of echinocytes, a buckling and denudation of
      endothelial cells, and a disturbation of endothelial prostacyclin release. It is
      not known so far whether the reactions observed in the context of RCM
      applications are reactions of venous endothelial cells alone or also of arterial
      endothelial cells. Therefore, arterial ECs on ECM were exposed to the same RCMs
      under identical conditions. The decrease of cell-cell contacts with an increase
      of denuded subendothelial matrix areas in the functionally confluent endothelial
      cell layer on ECM were more pronounced after a five minute exposure of
      endothelial cells to Iomeprol compared to Iodixanol. Changes in arterial ECs
      after the incubation in culture media supplemented with RCM were very subtle in
      comparison to changes in venous ECs.

PMID- 21876234
TI  - Efficacy of CD14+ blood monocytes/macrophages isolation: positive versus negative
      MACS protocol.
AB  - Cardiovascular implants such as stents or artificial vascular grafts established
      in clinical application to date are generally designed as long-term implants. An
      important requirement for the successful application of these devices is the
      haemocompatibility of their interface to the blood stream, which often is
      approached by polymeric coatings. Modern therapies are aiming at curative
      treatments (Regenerative Medicine) by inducing the in vivo formation of a new
      endothelial layer on the implant surface ensuring an optimal haemocompatibility
      based on the generated glycocalyx. A promising approach for providing the
      required biological stimulus is the secretion of pro-angiogenic factors (such as
      VEGF-A) by autologous CD14+ monocytes/macrophages (mo/mPhi), which can be induced
      by previous angiogenic stimulation. While protocols for negative and positive
      immune-isolation are already established, this study was aimed to evaluate the
      efficacy of a positive and a negative MACS based immune-isolation protocol by
      analysing the yield, the purity and the activation status of the isolated CD14
      mo/mPhi. Both protocols enabled the isolation of more than 80% (positive
      isolation) and 86% (negative isolation) CD14+ mo/mPhi representing approximately
      1.3 * 107 CD14+ mo/mPhi from 1 ml buffy coat. Less than 10% of these cells were
      also positive for CD69. Latter is an important selection criterion as CD69 is a
      marker characteristic for classically activated and catabolic active mo/mPhi
      which can negatively affect the endothelialisation process. As the negative
      immune-isolation protocol resulted in a cell fraction meeting the requirements on
      a pure cell fraction (percentage of contaminating cells < 15%) this isolation
      method is advantageous although it was more time consuming than the positive
      isolation protocol.

PMID- 21876235
TI  - Telmisartan prevents VCAM-1 induction and monocytic cell adhesion to endothelium
      exposed to non-uniform shear stress and TNF-alpha.
AB  - BACKGROUND: Atherosclerotic plaques develop at arterial regions subjected to non
      uniform shear stress, and are initiated by increased leukocyte-endothelial
      interactions. Here we applied the in vitro model of arterial bifurcations to
      investigate whether telmisartan, an anti-inflammatory angiotensin II receptor
      blocker with PPAR-gamma activating ability, prevents monocyte recruitment by
      endothelium. METHODS: Human umbilical vein endothelial cells (ECs) were exposed
      to 18 h non-uniform shear stress in bifurcating flow-through slides, followed by
      2 h stimulation with 2.5 ng/mL TNF-alpha. During flow, cells were treated with
      telmisartan. To study cell adhesion, ECs were perfused with medium containing THP
      1 monocytic cells. Adherent THP-1 monocytes were quantified by light microscopy.
      Endothelial protein expression was determined by immunofluorescence. RESULTS: Non
      uniform shear stress in combination with TNF-alpha dramatically induced monocytic
      cell recruitment by endothelial cells. In cells treated with telmisartan (0.5-2.5
      MUmol/L) during exposure to non-uniform shear stress, dose-dependent inhibition
      of monocytic cell adhesion was observed, with about 45% reduction at 1 MUmol/L.
      This effect was mediated by a significant reduction of endothelial VCAM-1
      expression. On the contrary, the induction of E-selectin by TNF-alpha in ECs
      exposed to non-uniform shear stress was not affected by telmisartan. The
      inhibitory effect of telmisartan on monocytic cell recruitment and VCAM-1
      induction was prevented in the presence of the PPAR-gamma antagonist GW9662.
      CONCLUSIONS: Treatment with telmisartan decreases the TNF-alpha-induced
      recruitment of monocytic cells and endothelial expression of VCAM-1 in regions of
      non-uniform shear stress in vitro. This mechanism can contribute to the
      beneficial pleiotropic effects of telmisartan in atherosclerosis-prone arterial
      regions.

PMID- 21876236
TI  - Evaluation of hyperbaric oxygen therapy for free flaps using planar optical
      oxygen sensors. Preliminary results.
AB  - OBJECTIVES: This study was designed to determine if a) hyperbaric oxygen
      increases the tissue oxygenation of free flaps and b) verification of this effect
      is possible by using a recently validated and innovative method for two
      dimensional pO2 measurement (Luminescence lifetime imaging = LLI). METHODS: Six
      patients with a free parascapular flap transplanted to the lower limb received
      hyperbaric oxygen (HBOT) therapy. The HBOT regimen consisted of treatment over 90
      minutes with 100% O2 (FiO2 1.0) at 240 kPa (Marx-Schema). The transcutaneous
      oxygen partial pressure (ptcO2) was measured over the entire flap with the use of
      luminescence lifetime imaging (LLI) before and 30, 60, 120 minutes after
      treatment. The LLI is based on the oxygen dependent quenching of phosphorescence
      of the indicator dye platinum (II)-octaethyl-porphyrin implemented in a
      polystyrene sensor foil. RESULTS: In all six free flaps we could find a
      significant increase of tissue oxygen over the entire flap in form of increased R
      values as well as subsequently calculated absolute ptcO2 values over a period of
      120 min after hyperbaric therapy. The ptcO2 values increased significantly from
      42.59 +/- 1.11 Torr before to 81.14 +/- 5.95 Torr after hyperbaric treatment (p <
      0.001). Even after 2 hours the ptcO2 values were significantly higher (83.45 +/-
      13.80 Torr) compared with values prior to HBOT (p < 0.006). CONCLUSIONS: The
      findings of this study demonstrated an increase of oxygen supply over the entire
      flap after hyperbaric oxygen therapy.

PMID- 21876237
TI  - TTP (time to PEAK) and RBV (regional blood volume) as valuable parameters to
      detect early flap failure.
AB  - BACKGROUND: Free flap transplantation is used more and more frequently in order
      to cover extensive wound defects. The basic prerequisite for successful flap
      salvage after flap failure is a short time interval from failure until revision.
      For this reason many different flap monitoring systems have been tested over the
      last years. OBJECTIVE: The aim of the experiment was to detect critical capillary
      perfusion using contrast enhanced ultrasound. Quantitative analysis should be
      performed by a special perfusion software (QONTRAST; Bracco, Italy) appraising
      digital raw data of contrast enhanced ultrasound (CEUS). Additionally diverse
      risk factors for free flap transplantation were determined. METHODS: Thirty-one
      patients were examined after free flap transplantation during the first 72 hours
      after operation. CEUS was performed with a linear transducer (6-9 MHz, LOGIQ
      E9/GE) and a bolus injection of 2.4 ml of contrast agent (SonoVue, Bracco,
      Italy). Operation and examination were performed by either an experienced plastic
      surgeon or an experienced ultrasound examiner. Depth dependent capillary
      perfusion was analysed and quantitative perfusions analysis was performed using
      the perfusions software QONTRAST (Bracco, Italy). Eleven revisions had to be
      performed: 7 due to haematoma and 4 due to superficial necrosis. RESULTS: Reduced
      capillary perfusion was seen in all 11 complications using CEUS. Significant
      difference comparing the no complication and the complication group was observed
      using TTP (time to PEAK) and RBV (regional blood volume) quantitative analysis.
      Mean RBV was 922.1 +/- 150.9 in the no complication and 303.0 +/- 53.9 in the
      complication group (p = 0.001). Mean TTP was 37.6 +/- 3.8 in the no complication
      and 21.3 +/- 3.4 in the complication group (p = 0.006). Tendency to higher
      complication rate was seen in older male patients with vascular or malignant
      primary disease. CONCLUSION: In this clinical trial, capillary perfusion after
      free flap transplantation as well as detection of vascular complications was
      demonstrated using CEUS. Quantitative perfusions analysis could be performed and
      flap viability could be assessed easily.

PMID- 21876238
TI  - Evaluation of the microvascularization of pathologic parathyroid glands in
      patients with primary hyperparathyroidism using conventional ultrasound and
      contrast-enhanced ultrasound.
AB  - PURPOSE: The objective was to characterize the microcirculation of parathyroid
      adenomas using contrast-enhanced ultrasound (CEUS) and to evaluate if it can be
      used for diagnosis and localization of pathologic glands. PATIENTS AND METHODS:
      Thirty patients with primary hyperparathyroidism scheduled for parathyroidectomy
      were enrolled. Preoperatively, all patients underwent B-Scan sonography, Colour
      coded Doppler Sonography (CCDS), Power Doppler (PD) and CEUS. The diagnostic
      confidence concerning B-Scan, CCDS, PD and CEUS was classified into six grades
      (0: no adenoma; 5: adenoma). RESULTS: Using CEUS, all adenomatous glands showed a
      typical dynamic microvascularization. B-Scan showed a mean grade of 2.18, CCDS
      2.29, PD 2.33, CEUS 4.29 (6-9 MHz transducer) and 3.52 (6-15 MHz). The
      differences between CEUS and conventional sonography were all statistically
      significant (p < 0.05). CEUS noted a sensitivity of 98.4% and specificity of
      98.4% for the detection of adenomatous glands. CONCLUSION: CEUS facilitates the
      detection and diagnosis of pathologic parathyroid glands due to their typical
      microvascularization.

PMID- 21876239
TI  - Post-operative monitoring of tissue transfers: advantages using contrast enhanced
      ultrasound (CEUS) and contrast enhanced MRI (ceMRI) with dynamic perfusion
      analysis?
AB  - BACKGROUND: The immediate evaluation of microvascular tissue flaps with respect
      to microcirculation after transplantation is crucial for optimal monitoring and
      outcome. The purpose of our investigation was to evaluate the clinical value of
      contrast-enhanced ultrasound (CEUS) and contrast-enhanced MRI (ceMRI) for
      monitoring the integrity of tissue flaps in plastic surgery. METHODS: To this
      end, we investigated 10 patients (47 +/- 16 a) between postoperative day 7 and 14
      who underwent flap surgery in order to cover tissue defects in various body
      regions. For CEUS we utilized the GE LOGIQ E9 equipped with a linear transducer
      (6-9 MHz). After application of 2.4 ml SonoVue, the tissue perfusion was detected
      in Low MI-Technique (MI < 0.2). The perfusion curves were quantitatively analyzed
      using digital video sequences (QONTRAST, Bracco, Italy) regarding peak % and
      relative blood flow (RBF). Furthermore, we investigated all tissue flaps using
      contrast-enhanced MRI (Magnetom Symphony TIM, Siemens) with a 3D-VIBE sequence
      and a time resolution of 7s. Thus, the transplants were completely captured in
      all cases. As perfusion parameters, the positive enhancement integral (PEI) as
      well as the maximum intensity projection time (MIP-time) were collected. For
      comparison of both applications, all parameters were displayed in color-coded
      resolution and analyzed by three independent readers. Depending on the flap
      thickness, 1-3 regions of interest (ROI) were investigated. Each ROI measured 1 *
      3 cm. RESULTS: The subcutaneous ROI-1 showed a significantly lower rating
      regarding RBF in the ceMRI compared to CEUS (Mann-Whitney Rank-Sum test, p <
      0.05). ROI-2 and -3 did not show any significant differences between the two
      applications. The frequency distribution showed good accordance in both
      modalities. Both imaging techniques detected 1 partial flap necrosis within the
      random area of cutaneous and subcutaneous layers, 1 hematoma as well as 1
      insufficient perfusion over all tissue layers. After subsequent reoperation,
      graft loss could be prevented. CONCLUSION: At present, both technologies provide
      an optimal assessment of perfusion in cutaneous, subcutaneous and muscle tissue
      layers, whereby the detection of fatty tissue perfusion is currently more easily
      detected using CEUS compared to ceMRI.

PMID- 21876240
TI  - Shear stress and force required for tether formation of neonatal and adult
      erythrocytes.
AB  - Red blood cells (RBC) of neonates have a shorter survival time and they are more
      susceptible to mechanical alterations than RBC of adults. Irreversible alteration
      of the membrane of RBC of preterm neonates, term neonates and adults due to
      tether formation was studied by means of a micropipette technique. Shear stress
      and forces were applied with this technique in an axisymmetric configuration and
      were calculated with an approximation method. The applied shear stress and forces
      that induced tether formation were lowest for RBC of preterm neonates (1.5 Pa,
      1.8 pN), in between for RBC of neonates (1.7 Pa, 2.1 pN) and highest for RBC in
      adults (1.9 Pa, 2.6 pN). Decreased mechanical stability of the membrane of
      neonatal RBC may in part cause the shorter life span, the greater tendency to
      endocytosis and the higher amount of irregularly shaped cells of neonatal RBC
      compared to RBC in adults.

PMID- 21876241
TI  - Influence of rheological parameters on the velocity of erythrocytes passing
      nailfold capillaries in humans.
AB  - One thousand two hundred and fifty-six subjects (apparently healthy subjects and
      patients with cardiovascular diseases) were registered in a prospective study
      including demographical and clinical data, rheological parameters (hematocrit,
      plasma viscosity, erythrocyte aggregation, erythrocyte deformability) as well as
      the erythrocyte velocity in human nailfold capillaries under resting and
      postischemic conditions. A multivariate regression analysis showed that under
      resting conditions there was no correlation between rheological parameters and
      erythrocyte velocity in capillaries. The blood flow regulation seemed to be so
      effective, that pathological changes of the blood fluidity showed no effect on
      the velocity of an erythrocyte passing the capillaries. During vessel paralysis
      in the early phase of the postischemic hyperemia following a stasis of three
      minutes in the vasculature distal to a pressure cuff at the upper arm a very
      clear correlation between the plasma viscosity and the maximum postischemic
      erythrocyte velocity in ipsilateral cutaneous capillaries could be observed (p <
      0.0001) while none of the other rheological parameters seemed to play a role. In
      a subgroup of diabetic patients the erythrocyte aggregation (measured during
      stasis) also correlated with the erythrocyte velocity (p = 0.0175) besides the
      plasma viscosity. This shows that a correlation of rheological parameters with
      the capillary perfusion could only be found during vessel paralysis. In of
      diabetic patients besides the plasma viscosity also the erythrocyte aggregation
      correlated with the mean capillary erythrocyte velocity. Theses results are in
      agreement with the hypothesis from Barras that plasma viscosity determines the
      perfusion of microvessels. Under certain conditions e.g. diabetic disorder, also
      the erythrocyte aggregation plays a role.

PMID- 21876242
TI  - Improved carotid atherosclerotic plaques imaging with contrast-enhanced
      ultrasound (CEUS).
AB  - PURPOSE: To evaluate neovascularisation within carotid atherosclerotic plaques
      with contrast enhanced ultrasound. METHODS: We used contrast-enhanced ultrasound
      to examine 33 patients with carotid atherosclerotic plaques. Plaque size and
      echogenicity were analyzed and we correlated neovascularization within the
      plaques. RESULTS: There were 41 atherosclerotic plaques, 27 plaques enhanced
      after the injection of a contrast agent. Among the group of enhancing plaques we
      found 8 soft- and 19 mixed plaques. The overall thickness ranging in enhanced
      plaques was from 1.8 to 4.6 mm. In all cases the contrast uptake in the plaques
      was later than in the carotid artery. Among the 14 unenhanced atherosclerotic
      plaques, 4 plaques presented as hard plaques, three calcified plaques, two soft
      plaques and five presented as mixed plaques. The overall thickness ranging in
      unenhanced plaques was from 1.7 to 6 mm. CONCLUSION: Contrast-enhanced ultrasound
      allows the non invasive, dynamic evaluation of neovascularisation within carotid
      plaques.

PMID- 21876243
TI  - Benefit of contrast enhanced ultrasound for detection of ischaemic lesions and
      arterio venous fistulas in renal transplants - a feasibility study.
AB  - PURPOSE: To evaluate the benefit of CEUS (contrast enhanced ultrasound) regarding
      depiction of ischaemic lesions and AVFs (arterio venous fistula) in renal
      transplants compared to standard ultrasound (US) (grey-scale and color Doppler).
      MATERIALS AND METHODS: In this study 22 patients suspected of having acute
      vascular complication after renal transplantation were investigated using
      standard ultrasound (grey-scale US and color Doppler US) and CEUS, respectively.
      Validity of the respective US-techniques regarding depiction of ischaemic lesions
      and AVF was compared. Dynamic CTA (computed tomography angiography) served as the
      standard of reference. RESULTS: In 10 renal transplants arterial embolism
      associated with kidney infarctions were observed. Very good correlation to
      dynamic CTA was yielded using CEUS, whereas grey scale US and color Doppler US
      was limited in the accurate depiction of renal infarctions. Additionally CEUS was
      superior in displaying arteriovenous fistulas compared to standard US.
      CONCLUSION: CEUS as a fast and bedside available imaging modality not associated
      with dose exposure or renal toxicity facilitates improved detection of ischaemic
      lesions and AVFs compared to standard US and thus should be considered for short
      term follow up of renal transplants.

PMID- 21876244
TI  - Biological evaluation of degradable, stimuli-sensitive multiblock copolymers
      having polydepsipeptide- and poly(epsilon-caprolactone) segments in vitro.
AB  - Polydepsipeptides, alternating copolymers consisting of alpha-amino acids and
      alpha-hydroxy acids, are degradable polymers. Depsipeptide-based polymers of
      varied architectures can be synthesized via ring-opening polymerization of
      various morpholine-2,5-dione derivatives. Thermoplastic phase-segregated
      multiblock copolymers with poly(epsilon-caprolactone) (PCL) and poly(iso-butyl
      morpholinedione) segments have been synthesized from the macrodiols and an
      aliphatic diisocyanate as a coupling agent. The respective multiblock copolymers
      showed shape-memory capabilities and good elastic properties, making them
      attractive candidates for potential application as biomaterials for controlled
      drug release systems, scaffolds to be applied in tissue engineering or
      biofunctional implants. Thus, these abilities cumulate to form multifunctional
      materials, combining degradability with shape-memory capability. The advantages
      of depsipeptide-based multiblock copolymers compared to previously reported
      poly(ether)ester-derived biomaterials having shape-memory property may result
      from their different degradation products, as the resulting alpha-amino acids may
      act as a buffer for the hydroxy acids, thereby stabilizing pH values. In this
      context, we report on the biological evaluation of material samples in accordance
      with international standards (EN DIN ISO 10993-5 and 10993-12). Here, extracts of
      the substrates were exposed to a continuous fibroblast like cell line (L929) to
      study cytocompatibility of extractable substrates. Cell viability, morphology,
      LDH-release (as a parameter for the functional integrity of the cell membrane),
      activity of the mitochondrial dehydrogenases (as a parameter of the cell
      activity) and assembly of the actin- and vinculin cytoskeleton indicated no
      incompatibilities between the extracts and L929 cells. These results suggest that
      depsipeptide-based multiblock copolymers are promising candidates for soft,
      multifunctional implant materials.

PMID- 21876245
TI  - Pig specific vascular anatomy allows acute infrarenal aortic occlusion without
      hind limb ischemia and stepwise occlusion without clinical signs.
AB  - OBJECTIVE: In a porcine, aortic graft model we found 5 animals to develop and
      survive unnoticed, complete infrarenal aortic occlusion and 2 pigs with an acute
      occlusion but rather unspecific clinical symptoms. We investigated the pigs'
      vascular system to classify the anatomic capabilities to compensate for an acute
      abdominal aortic occlusion. DESIGN OF STUDY: Retrospective analysis of CT scans
      and clinical data to specify unexpected results in a case series of infrarenal
      occlusion in a porcine model. SETTING: Collaborative study of experimental and
      clinical departments. SUBJECTS: Fifteen healthy female minipigs. INTERVENTIONS:
      All pigs underwent an infrarenal aortic graft intervention. Anesthesia and
      perioperative management of the animals were preformed along the standard
      operating procedures of the local Department of Experimental Medicine. All
      animals received perioperative antibiotics, ASS, and carprofen for postoperative
      analgesia. Arterial pressure, heart rate, body temperature, and diuresis were
      monitored during surgery and therapeutic interventions. MAIN OUTCOME MEASURES:
      Contrast media based computed tomography (CT) with total body scans were
      performed at 1, 4, 10, 12 weeks after surgery. Comparable scans of cardiovascular
      healthy subjects (humans and pigs) and patients with a Leriche's syndrome were
      analyzed. RESULTS: Neither acute (within the first 12 h after surgery) nor
      stepwise total aortic occlusion show unmistakable clinical signs. In pigs, the
      epigastric artery (EGA) - which is in connection with suprarenal lumbal arteries,
      subclavian and external iliac artery - is highly developed associated to the high
      number of mammary glands of about 7 on one side. In humans, the ratio of aortic
      to EGA-diameter is 1 : 0.15. In minipigs we found a ratio of 1 : 0.43 which
      changed during aortic occlusion resulting in a ratio of 1 : 0.58. Pigs with a
      slowly developing occlusion demonstrated an enlargement of the ureteric artery of
      about 210% completing a sufficient collateral system. CONCLUSION: While in the
      human Leriche's syndrome months are needed to enlarge the EGAs for a partial
      collateral support of an infrarenal aortic occlusion the pig's EGA is a naturally
      sufficient collateral system capable to cover immediately for an acute infrarenal
      aortic occlusion. Further collateral enlargement even provides a permanent,
      sufficient hind limb perfusion in pigs. As the sufficient collateral system
      probably reduce pressure and shear rates in the infrarenal aortic segment after
      cross clamping, pigs might have a higher predisposition to produce early
      thrombosis related graft occlusions tan humans.

PMID- 21876246
TI  - Comparison of time-intensity-curve- (TIC-) analysis of contrast-enhanced
      ultrasound (CEUS) and dynamic contrast-enhanced (DCE) MRI for postoperative
      control of microcirculation in free flaps - first results and critical comments.
AB  - Postoperative monitoring of transplanted free flaps is an essential tool to
      reveal possible complications. The aim of this study was to compare the value of
      time-intensity-curve- (TIC-) analysis based on grey scale data of contrast
      enhanced ultrasound (CEUS) and dynamic contrast-enhanced (DCE-) magnetic
      resonance imaging (MRI). Postoperative imaging was performed in 11 patients
      following free flap transplantation and TIC analysis was obtained in identical
      regions of interest (ROI) of CEUS and DCE MRI data. Microcirculation was assessed
      in superficial (0-1 cm), middle (1-2 cm), and deep (2-3 cm) ROIs in one or two
      different positions within the flap resulting in a total of 46 ROIs evaluated (in
      very thin flaps only superficial and middle ROIs were assessed). For both imaging
      methods, mean signal increase was found to be significantly higher in ROIs of
      normally perfused flaps (n = 40) compared to ROIs with compromised
      microcirculation (n = 6). Although TIC analysis allows quantification of
      microcirculation in different regions of the flap, in this preliminary study no
      distinct threshold could be defined to differentiate flaps with normal and
      compromised microcirculation.

PMID- 21876247
TI  - Duplex and contrast enhanced ultrasound (CEUS) in evaluation of in-stent
      restenosis after carotid stenting.
AB  - PURPOSE: The aim of the study was to evaluate whether contrast enhanced
      ultrasound (CEUS) can improve the visualization of in-stent restenosis after
      carotid stenting of the internal carotid artery (ICA) in comparison to color
      coded duplex sonography (CCDS) and power Doppler. MATERIAL AND METHODS: The study
      included the follow up of thirty patients after carotid artery stenting (CAS).
      Intrastenotic flow detection and lengths of in-stent restenosis were the main
      criteria. A high-end ultrasound machine (Siemens, ACUSON, Sequoia or S2000) with
      a multi-frequency linear 9 MHz or 15 MHz transducer was used to carry out
      contrast-enhanced ultrasound with SonoVue. In cases of treatment of a high degree
      in-stent stenosis intra-arterial digital subtraction angiography (DSA) was used.
      RESULTS: All patients were examined using all diagnostic ultrasound tools of the
      study. In five patients (17%) an in-stent restenosis of the internal carotid
      artery (ICA) was found. Two patients need a reintervention. The results show that
      the contrast enhanced ultrasound could improve the diagnostic assessment
      capabilities in comparison to CCDS and power Doppler for patients with in-stent
      restenosis after carotid stenting of the ICA. CONCLUSION: Contrast enhanced
      ultrasound is a reliable method for the evaluation of in-stent restenosis after
      carotid stenting of the ICA. CEUS provides a reduction in intrastenotic flow
      artefacts, resulting in better visualisation and detection of the complete length
      of the stenosis in comparison with CCDS and power Doppler. In order to elucidate
      hemodynamic changes, additional Doppler examinations are still necessary.

PMID- 21876248
TI  - Aging promotes amyloid-beta peptide induced mitochondrial dysfunctions in rat
      brain: a molecular link between aging and Alzheimer's disease.
AB  - The entangled relationship of brain aging, mitochondrial dysfunction, and amyloid
      beta peptide (Abeta42) toxicity occupies the center stage in the pathogenesis of
      Alzheimer's disease (AD). The present study examines some of the toxic effects of
      Abeta42 on brain mitochondria and provides evidence that aged brain mitochondria
      are significantly more vulnerable to Abeta42 toxicity. In particular, the study
      has shown that the aggregated, but not the monomeric, form of Abeta42 in varying
      concentrations (10-40 MUM) during in vitro incubation causes a loss of
      mitochondrial membrane potential, a decrease in phosphorylation capacity and ATP
      synthesis, and the release of cytochrome c from the mitochondria but without any
      noticeable change in the activities of respiratory chain complexes. Such effects
      of Abeta42 are strikingly more conspicuous on aged rat (22-24 months) brain
      mitochondria compared to that on brain mitochondria of young rats (4-6 months).
      More interestingly is the observation that in contrast to young rat brain
      mitochondria, a significantly higher level of Abeta42 remains associated with
      aged brain mitochondria under basal incubation condition as well as after
      exposure to exogenously added peptide. Extrapolated to an in vivo scenario, the
      results have clear implications in AD pathogenesis and also partly explain why
      brain aging is a dominant risk factor for this disease condition.

PMID- 21876250
TI  - No association between hypertension and risk for Alzheimer's disease: a meta
      analysis of longitudinal studies.
AB  - This study examined the association between hypertension and AD by using a
      quantitative meta-analysis of longitudinal studies. EMBASE and MEDLINE were
      searched for articles published up to February 2011. All studies that examined
      the association of hypertension or antihypertensive medication use with the onset
      of AD were included. Pooled relative risks (RR) were calculated using fixed and
      random effects models. Twelve studies met our inclusion criteria for this meta
      analysis. All subjects were without dementia at baseline. Among them, 9 studies
      compared the incidence of AD between subjects with (7,270) and without (8,022)
      hypertension. The quantitative meta-analysis showed that there was no significant
      difference in incidence of AD (RR: 1.02, 95% confidence interval (CI): 0.91-1.14)
      between subjects with and without hypertension. Seven studies compared the
      incidence of AD between subjects with (8,703) and without (13,041)
      antihypertensive medication use. The quantitative meta-analysis showed that there
      was no significant difference in incidence of AD (RR: 0.90, 95% CI: 0.79-1.03)
      between subjects with and without antihypertensive medication use. The
      quantitative meta-analysis showed that neither hypertension nor antihypertensive
      medication use was associated with risk for incident AD.

PMID- 21876249
TI  - Amyloid-beta toxicity and tau hyperphosphorylation are linked via RCAN1 in
      Alzheimer's disease.
AB  - Amyloid-beta peptide (Abeta) toxicity and tau hyperphosphorylation are hallmarks
      of Alzheimer's disease (AD). How their molecular relationships may affect the
      etiology, progression, and severity of the disease, however, has not been
      elucidated. We now report that incubation of fetal rat cortical neurons with
      Abeta upregulates expression of the Regulator of Calcineurin gene RCAN1, and this
      is mediated by Abeta-induced oxidative stress. Calcineurin (PPP3CA) is a serine
      threonine phosphatase that dephosphorylates tau. RCAN1 proteins inhibit this
      phosphatase activity of calcineurin. Increased expression of RCAN1 also causes
      upregulation of glycogen synthase kinase-3beta (GSK3beta), a tau kinase. Thus,
      increased RCAN1 expression might be expected to decrease phospho-tau
      dephosphorylation (via calcineurin inhibition) and increase tau phosphorylation
      (via increased GSK3beta activity). Indeed, we find that incubation of primary
      cortical neurons with Abeta results in increased phosphorylation of tau, unless
      RCAN1 gene expression is silenced, or antioxidants are added. Thus we propose a
      mechanism to link Abeta toxicity and tau hyperphosphorylation in AD: In our
      hypothesis, Abeta causes mitochondrial oxidative stress and increases production
      of reactive oxygen species, which result in an upregulation of RCAN1 gene
      expression. RCAN1 proteins then both inhibit calcineurin and induce expression of
      GSK3beta. Both mechanisms shift tau to a hyperphosphorylated state. We also find
      that lymphocytes from persons whose ApoE genotype is epsilon4/epsilon4 (with high
      risk of developing AD) show higher levels of RCAN1 and phospho-tau than those
      carrying the ApoE epsilon3/epsilon3 or epsilon3/epsilon4 genotypes. Thus
      upregulation of RCAN1 may be a valuable biomarker for AD risk.

PMID- 21876251
TI  - What to look for beyond "pathogenic" factors in senile dementia? A functional
      deficiency of Ca2+ signaling.
AB  - We have contended that senile conditions--illnesses after age 60 and fully age
      penetrating, such as tooth, hearing or memory loss--are not distinct "diseases"
      in medical nature, because they are caused by aging. Since the pace of aging
      varies among individuals and is much influenced by risk factors, senile
      conditions will only affect some but not all elderly. However, perhaps due to its
      unusually heavy burdens and tremendous social pressures, senile dementia (SD) has
      been singled out from other senile conditions and redefined as a curable
      "disease" (Alzheimer's). This highly popular definition has thus opened a
      Pandora's box that has been confusing us up until now and warrants further
      scrutiny. In this article we discuss: a) what should we logically look for in SD
      beyond "pathogenic" factors?; b) why Ca2+, a central regulator in
      neurotransmission, should be the primary player in SD; c) why the functionality
      of Ca2+ signaling, or its vibrant wave frequency and amplitude, must undergo down
      regulation during aging, though this is intriguingly accompanied by an increase
      of Ca2+ "levels"; d) why intervention for SD should target Ca2+ function by
      promoting energy metabolisms and by Ca2+ agonists such as caffeine and nicotine,
      but not by "antagonists" as widely believed; and e) why our study should focus on
      aging, not "cell death", a seemingly attractive paradigm but perhaps too late for
      intervention. We also seek answers for why unproven hypotheses can become dogmas
      and inhibit self-correcting mechanisms of science.

PMID- 21876252
TI  - Neuronal differentiation of human mesenchymal stromal cells increases their
      resistance to Abeta42 aggregate toxicity.
AB  - Cell therapy is a promising approach for the treatment of neurodegenerative
      conditions such as Alzheimer's and Parkinson's diseases. However, the presence of
      toxic aggregates in tissue raises the question of whether grafted stem cells are
      susceptible to amyloid toxicity before they differentiate into mature neurons. To
      address this question, we investigated the relative vulnerability of human
      mesenchymal stromal cells and their neuronally differentiated counterparts to
      Abeta(42) oligomers and whether susceptibility correlates with membrane GM1
      content, a key player in oligomer toxicity. We found that our cell model was
      highly susceptible to aggregate toxicity, whereas neuronal differentiation
      induced resistance to amyloid species. This data correlated well with the content
      of membrane GM1, levels of which decreased considerably in differentiated cells.
      These findings extend our knowledge of stem cell vulnerability to amyloid
      species, which remains a controversial issue, and confirm that amyloid-GM1
      interactions play an important role in cell impairment.

PMID- 21876253
TI  - Episodic memory decline predicts cortical amyloid status in community-dwelling
      older adults.
AB  - Intra-individual decline in memory and cognition is characteristic of prodromal
      Alzheimer's disease (AD) and may allow detection of very early AD pathology.
      Episodic memory task scores on a brief computerized cognitive battery (CogState)
      were prospectively evaluated at baseline, and 3-, 6-, 9-, 12-, and 24-months post
      baseline. Linear mixed models were conducted to compute age-adjusted slopes.
      Subjects with slopes declining >=90th percentile ("memory decliners") and age-
      and gender-matched subjects without such decline ("non-decliners") were studied
      with clinical, neuropsychological, and neuroimaging evaluations. Of 195 who
      completed 24-month evaluation (age 51 to 80 years), 15 memory decliners (mean age
      62.7 years, SD 7.6) were identified, and matched with 33 non-decliners (mean age
      63.3 years, SD 8.2). Amyloid-PET imaging was qualitatively abnormal with excess
      cortical amyloid accumulation in 7 memory decliners (46.7%) and 4 (12.1%) non
      decliners (odds ratio 6.34), and quantitatively abnormal with standardized uptake
      value ratios >1.4 in 5 memory decliners (33.3%) and 2 (6.1%) non-decliners (odds
      ratio 8.3). One of the memory decliners and none of the non-decliners fulfilled
      criteria for mild cognitive impairment, but the groups did not differ with
      respect to subjective memory impairment, neuropsychological evidence of episodic
      memory impairment, or MRI imaging abnormalities. Intra-individual decline in
      episodic memory can be detected using a brief computerized cognitive performance
      test optimized to detect change in community-dwelling non-demented older persons
      and appears predictive of the presence of cerebral amyloid in about half of these
      persons. This approach may help detect early prodromal AD pathology in wider
      scale community screening programs.

PMID- 21876254
TI  - Probable participation of 14-3-3 in tau protein oligomerization and aggregation.
AB  - Aggregation of tau proteins followed by formation of paired helical filaments and
      neurofibrillary tangles is considered as a hallmark of certain neurodegenerative
      disorders such as different tauopathies and Alzheimer's disease (AD). Tau
      aggregation is dependent on the presence of polyanions, cellular redox state,
      limited proteolysis, and different posttranslational modifications among which
      tau phosphorylation plays a particularly important role. Although it is still
      debatable whether tau aggregation is harmful or protective for the cell, detailed
      analysis of molecular mechanisms underlying this process seems to be of great
      importance for understanding AD pathogenesis. This review is focused on universal
      adapter proteins 14-3-3 that seem to be significant partners to tau protein in
      neurons. 14-3-3 interacts with nonphosphorylated tau and promotes its interaction
      with and phosphorylation by a number of protein kinases. 14-3-3 induces
      aggregation of nonphosphorylated tau and does not affect aggregation of tau
      phosphorylated at specific sites. Due to its high concentration in neurons, 14-3
      3 can compete with tubulin for interaction with tau. Binding to phosphorylated
      tau, 14-3-3 might inhibit its dephosphorylation by protein phosphatases and by
      this means indirectly affect interaction of tau with microtubules and tau
      aggregation. Finally, 14-3-3 might promote sequestration of dangerous small tau
      oligomers and stabilize tau aggregates. We propose that 14-3-3 should be
      considered an important participant of the complex process of tau aggregation and
      as a potential therapeutic target in treating AD.

PMID- 21876255
TI  - Seizures can precede cognitive symptoms in late-onset Alzheimer's disease.
AB  - This study describes late-onset Alzheimer's disease (LOAD) in the mild cognitive
      impairment (MCI) stage, debuting with seizures in a 72 year-old woman. Prodromal
      AD was consistently diagnosed with four among amyloidosis and neurodegeneration
      biomarkers about 1 year after onset of seizures. Genetic assessment demonstrated
      apolipoprotein E epsilon2/epsilon3 genotype and three intronic single nucleotide
      substitutions, two in presenilin 1 and one in amyloid-beta protein precursor
      genes. This case of seizures at onset of LOAD with severe signs of brain
      amyloidosis and neurodegeneration but with just MCI leads to a re-appraisal of
      the intriguing relationship between AD pathology and neuron excitability in
      humans.

PMID- 21876256
TI  - Cost and care of patients with Alzheimer's disease: clinical predictors in German
      health care settings.
AB  - The study aims to report service use and costs for patients with Alzheimer's
      disease (AD) and to explore the incremental influence of sociodemographic and
      illness-related determinants in ambulatory and inpatient settings within the
      German health care system. 395 patients with dementia were recruited at the
      following sites: 1) University hospital, 2) general practitioners' offices, 3)
      office-based neurologists, 4) a regional psychiatric hospital, and 5) nursing
      homes. Sociodemographic, economic, and clinical parameters were assessed using a
      standardized questionnaire. Informal care was not evaluated. Disease severity was
      measured using the Mini-Mental Status Examination and the Alzheimer's Disease
      Assessment Scale - Cognitive Subscale. Neuropsychiatric status was assessed using
      the Geriatric Depression Scale, the Neuropsychiatric Inventory, and the
      Alzheimer's Disease Cooperative-Study-Activities of Daily Living. Annual total
      costs were estimated to be ?13,080 per patient. The most important cost component
      was (long-term) care, constituting about 43% of total costs. Indirect costs
      comprised about 18% of total costs and were mainly due to reductions in working
      time of caregivers. Poorer functional status was associated with higher total and
      caregiving costs. In multivariate analyses, we identified younger age, female
      gender, and impaired activities of daily living as independent predictors of
      higher costs. Given that care for patients with AD is complex and expensive, our
      models were only able to explain about 17-43% of the variability in total costs.
      This suggests that further social and individual factors considerably influence
      the costs associated with AD. Direct medical care costs and long-term care costs
      related differently to the patient's clinical characteristics. Longitudinal and
      population-based studies are necessary for thoroughly evaluating the burden of
      disease.

PMID- 21876258
TI  - Assessing executive abilities following acute stroke with the trail making test
      and digit span.
AB  - The Trail Making Test and Digit Span are neuropsychological tests widely used to
      assess executive abilities following stroke. The Trails B and Digits Backward
      conditions of these tests are thought to be more sensitive to executive
      impairment related to frontal lobe dysfunction than the Trails A and Digits
      Forward conditions. Trails B and Digits Backward are also thought to be more
      sensitive to brain damage in general. Data from the Stroke and Lesion Registry
      maintained by the Washington University Cognitive Rehabilitation Research Group
      were analyzed to compare the effects of frontal versus nonfrontal strokes and to
      assess the effects of stroke severity. Results showed that the performance of
      patients with frontal and nonfrontal strokes was comparable in each condition of
      both the Trail Making Test and Digit Span, providing no support for the widely
      held belief that Trails B and Digits Backward are more sensitive to frontal lobe
      damage. Further, Trails A was as strongly correlated with stroke severity as
      Trails B, whereas Digits Backward was more strongly correlated with stroke
      severity than Digits Forward. Overall, the Trail Making Test and Digit Span are
      sensitive to brain damage but do not differentiate between patients with frontal
      versus nonfrontal stroke.

PMID- 21876259
TI  - Validating age-related functional imaging changes in verbal working memory with
      acute stroke.
AB  - Functional imaging studies consistently find that older adults recruit bilateral
      brain regions in cognitive tasks that are strongly lateralized in younger adults,
      a characterization known as the Hemispheric Asymmetry Reduction in Older Adults
      model. While functional imaging displays what brain areas are active during
      tasks, it cannot demonstrate what brain regions are necessary for task
      performance. We used behavioral data from acute stroke patients to test the
      hypothesis that older adults need both hemispheres for a verbal working memory
      task that is predominantly left-lateralized in younger adults. Right-handed
      younger (age ? 50, n = 7) and older adults (age > 50, n =21) with acute
      unilateral stroke, as well as younger (n =6) and older (n =13) transient ischemic
      attack (TIA) patients, performed a self-paced verbal item-recognition task. Older
      patients with stroke to either hemisphere had a higher frequency of deficits in
      the verbal working memory task compared to older TIA patients. Additionally, the
      deficits in older stroke patients were mainly in retrieval time while the
      deficits in younger stroke patients were mainly in accuracy. These data suggest
      that bihemispheric activity is necessary for older adults to successfully perform
      a verbal working memory task.

PMID- 21876261
TI  - On the nature of fear of falling in Parkinson's disease.
AB  - In the elderly, fear of falling (FoF) can lead to activity restriction and affect
      quality of life (QoL). Our aim was to identify the characteristics of FoF in
      Parkinson's disease and assess its impact on QoL. We assessed FoF in 130 patients
      with Parkinson's disease (PD) on scales measuring perceived self-efficacy in
      performing a range of activities (FES), perceived consequences of falling (CoF),
      and activity avoidance (SAFFE). A significant difference was found in FoF between
      PD patients who had previously fallen and those who had not and between frequent
      and infrequent fallers. Patient-rated disability significantly influenced FoF.
      Difficulty in rising from a chair, difficulty turning, start hesitation,
      festination, loss of balance, and shuffling were the specific mobility problems
      which were associated with greater FoF in PD. Disability was the main predictor
      of FoF, additionally depression predicted perceived consequences of falling,
      while anxiety predicted activity avoidance. The FoF measures explained 65% of the
      variance of QoL in PD, highlighting the clinical importance of FoF. These results
      have implications for the clinical management of FoF in PD.

PMID- 21876262
TI  - The evolution of alexia in two cases of posterior cortical atrophy.
AB  - Posterior cortical atrophy (PCA) is an uncommon presentation of Alzheimer's
      disease (AD), characterised by prevalent anatomo-functional involvement of
      posterior cortical areas. Accordingly, the main clinical features at onset are
      disorders of high-order visual processing, such as alexia and impairments of
      visuo-spatial and visuo-constructional abilities. The clinical features in the
      early stages of disease are variable, and they have been suggested to stem from
      prevalent ventral or dorsal brain pathology, and/or asymmetric hemispheric
      involvement. With disease progression, these differences tend to blur with the
      increasing severity of neuropsychological dysfunction. We report two PCA patients
      showing different patterns of reading impairment (respectively, letter-by-letter
      reading and neglect dyslexia). A follow-up study suggested that the qualitative
      features of alexia remain distinctive with disease evolution. In addition, single
      photon emission tomography (SPECT) studies revealed different patterns of
      hypoperfusion, consistent with the alexia types. A careful reading assessment can
      provide important insights to the pattern of progression of the disease in
      patients with PCA up to the late stages of the pathology.

PMID- 21876263
TI  - False reports from patients with frontotemporal dementia: delusions or
      confabulations?
AB  - Patients with behavioral variant frontotemporal dementia (bvFTD) can make false
      statements consistent with delusions or confabulations. It is unclear whether
      bvFTD is primarily associated with either delusions or with confabulations and
      whether they can be explained by the pathophysiology of this disease. In order to
      clarify this, we retrospectively surveyed the records of 48 patients with bvFTD
      for the presence of any false reports and identified four patients. Their false
      reports included continued interaction with a favorite but dead relation,
      fictitious marriages with movie stars, and two who claimed that their partner was
      having an affair. When confronted with the falsity of their statements, the
      patients conveyed a lack of certainty regarding their external or internal source
      but persisted in the constancy of their reports. On functional neuroimaging, the
      patients had predominant frontal involvement. This report found that patients
      with bvFTD can have both fantastic, wish fulfilling confabulations and typical
      content-specific delusions. We propose that both phenomena result from known
      disturbances of ventromedial prefrontal cortex in bvFTD, including deficits in
      source monitoring and in activating an automatic "doubt tag" for false reports.

PMID- 21876264
TI  - Multidisciplinary assessment and diagnosis of conversion disorder in a patient
      with foreign accent syndrome.
AB  - Multiple reports have described patients with disordered articulation and
      prosody, often following acute aphasia, dysarthria, or apraxia of speech, which
      results in the perception by listeners of a foreign-like accent. These features
      led to the term foreign accent syndrome (FAS), a speech disorder with perceptual
      features that suggest an indistinct, non-native speaking accent. Also correctly
      known as psuedoforeign accent, the speech does not typically match a specific
      foreign accent, but is rather a constellation of speech features that result in
      the perception of a foreign accent by listeners. The primary etiologies of FAS
      are cerebrovascular accidents or traumatic brain injuries which affect cortical
      and subcortical regions critical to expressive speech and language production.
      Far fewer cases of FAS associated with psychiatric conditions have been reported.
      We will present the clinical history, neurological examination,
      neuropsychological assessment, cognitive-behavioral and biofeedback assessments,
      and motor speech examination of a patient with FAS without a known vascular,
      traumatic, or infectious precipitant. Repeated multidisciplinary examinations of
      this patient provided convergent evidence in support of FAS secondary to
      conversion disorder. We discuss these findings and their implications for
      evaluation and treatment of rare neurological and psychiatric conditions.

PMID- 21876260
TI  - Emotional dysfunction in Parkinson's disease.
AB  - In addition to motor symptomatology, idiopathic Parkinson's disease is
      characterized by emotional dysfunction. Depression affects some 30 to 40 percent
      of Parkinson patients and other psychiatric co-morbidities include anxiety and
      apathy. Neuropsychological and neuroimaging studies of emotional dysfunction in
      Parkinson patients suggest abnormalities involving mesolimbic and mesocortical
      dopaminergic pathways. There is also evidence suggesting that the interaction
      between serotonin and dopamine systems is important in the understanding and
      treatment of mood disorders in Parkinson's disease. In this review we discuss the
      neuropsychiatric abnormalities that accompany Parkinson's disease and describe
      their neuropsychological, neuropharmacologic, and neuroimaging concomitants.

PMID- 21876265
TI  - Drawing with oblique coordinates: on a single case.
AB  - We describe a patient with right hemisphere damage affected by mild left visuo
      spatial neglect and constructional apraxia. During the rehabilitation, he failed
      to draw a draught-board using horizontal and vertical trajectories, but he
      performed it successfully using oblique trajectories. These observations
      suggested an impairment of vertical/horizontal spatial coordinates system. In
      copying tasks including figure elements in different orientations he drew more
      accurately components in oblique orientation, whereas failed to reproduce
      components in horizontal orientation. The patient performed visuospatial
      perceptual and perceptual-imaginative tasks successfully. From these findings, it
      is possible to suggest that the oblique coordinate system of reference operates
      independently of vertical and horizontal coordinate systems in building a complex
      figure and that, therefore, cardinal orientation do not constitute a reference
      norm to define oblique orientation, as previously suggested.

PMID- 21876267
TI  - An evaluation of nursing tasks.
AB  - Functional capacity evaluations have been criticized as being too general in
      theory and not being accurate enough to determine what tasks an employee can
      perform. This paper will describe results of a descriptive study that was
      conducted in a laboratory setting to objectively determine the physical demands
      of patient transfer tasks performed by nurses. Fifty three tasks were analyzed
      and broken down into sub-tasks to quantify the peak force required to perform
      each sub-task in order to determine which tasks pose healthcare workers at
      highest risk of injury. Dissecting the transfer task into segments allows us to
      see which part of the task requires high forces on the part of the caregiver. The
      task can then be modified to eliminate the risk of injury to the caregiver. This
      modification can be accomplished by using healthcare technology, such as floor
      based or overhead lifts, friction reducing devices, sit to stand lifts, properly
      designed slings, and motorized beds/trolleys. Technological solutions are
      available for some of these high risk tasks and should be implemented where
      applicable to reduce the force demand and eliminate or reduce the risk of injury
      to healthcare workers in nursing.

PMID- 21876268
TI  - Work and health: A comparison between Norwegian onshore and offshore employees.
AB  - OBJECTIVE: The effect of work-related variables on self reported health
      complaints were examined among Norwegian onshore and offshore oil workers.
      Differences in work and health perceptions were also examined as part of the
      paper. PARTICIPANTS: Employees working onshore and offshore in the maintenance
      and modification division of a large contractor company took part in the study
      (N=414, response rate 47.1%). METHODS: The design of the study was a cross
      sectional survey. A questionnaire was distributed to onshore personnel while at
      work - in cooperation with the personnel safety representative - and sent to the
      home addresses of the offshore personnel. RESULTS: Offshore workers perceived
      significantly more hazards associated with the work and experienced less control
      over the work pace compared to onshore workers. Onshore workers experienced
      significantly more pressure at work and their work tasks as more repetitive.
      Differences in health perceptions were identified in terms of job type in the
      onshore and offshore groups respectively. Different work-related factors
      influenced the self-reported health complaints among onshore and offshore
      workers. CONCLUSION: Workers in different work environments and in different job
      types encounter different type of threats to employee health, indicating that job
      type must be taken into account when studying the relationship between work
      related factors and employee health.

PMID- 21876269
TI  - Attitudes towards disability management: A survey of employees returning to work
      and their supervisors.
AB  - OBJECTIVES: Return to work after a leave on disability is a common phenomenon,
      but little is known about the attitudes of employees or their supervisors towards
      the disability management process. We report on employee and supervisor feedback
      from one disability management experience. PARTICIPANTS: 389 consecutive
      employees from the Ontario offices of a single private Canadian insurance company
      returning to work from short-term disability, and their supervisors. METHODS: We
      surveyed employees and their supervisors about their experience with, and
      attitudes towards, the disability management process. RESULTS: Of those surveyed,
      88 employees and 75 supervisors provided data (response rates of 22.6% and 19.3%
      respectively). The majority of respondents (79.1% of employees and supervisors)
      endorsed positive attitudes towards their disability management experience. More
      than 25% of employees disagreed with the following three items: case managers
      contributed to recovery, case managers removed barriers to recovery, and
      sufficient support was provided in the return to work process. More than 25% of
      employees and managers reported that a commitment to modify an unhelpful work
      situation was not followed through. CONCLUSION: The majority of participating
      employees returning to work from short-term disability, and their supervisors,
      reported a high level of satisfaction with the disability management process.
      Areas that may benefit from attention include some aspects of case manager
      employee interaction and ensuring that support during the return to work process
      is provided, including modification to work situations when appropriate.

PMID- 21876270
TI  - Living with organizational politics: An exploration of employees' behavior.
AB  - OBJECTIVE: This study aims to explore the employee's perception of organizational
      politics, the phase that they go through while working and the ways they adopt to
      cope with it. PARTICIPANTS: Participants were working as employees in three
      automobile manufacturing companies having offices in Pune, India. They were
      selected via randomized quota sampling to reflect a mix of age, positions,
      genders and experience within the organization. METHODS: Data collection was done
      through qualitative methods which included in-depth interviews with 26 employees.
      Analysis of the data was done using the coding process. RESULTS: Findings of this
      study led to the emergence of four major themes i.e. (a) The Perceived threat,
      (b) Attitude towards players, (c) Coping Strategies and (d) Intentions to leave.
      CONCLUSIONS: Based on the study findings, the researcher concludes that politics
      is being perceived as an evil and is negatively affecting the morale of the
      employees. Hence, it is imperative that the organizational forerunners and
      department heads continue to use research findings to get to know the culture
      prevailing in the organization and understand the emotional status and feelings
      that employees develop while working in such an environment.

PMID- 21876271
TI  - Manual handling incident claims in the healthcare sector: Factors and outcomes.
AB  - Manual handling (MH) incidents may result in injury, absenteeism and/or
      compensation claim. OBJECTIVE: This study investigated the factors associated
      with MH incidents among healthcare workers who had made a claim, and the
      management and outcome of those workers. PARTICIPANTS: A national sample of
      healthcare sector MH incident claim files (n=247) were accessed and 35~files met
      the inclusion criteria. METHODS: Data were collected and presented graphically or
      descriptively using percentages (and 95% Confidence intervals, CI). Chi-square
      (chi2) tests were used for comparing proportions between groups. SPSS (v14.0) was
      used for analysis. Significance at p<0.05 is assumed. RESULTS: Attendants
      accounted for the highest number of claimants. The majority of claims (74%, 95%
      CI 68%, 81%) were for back injury; 11% (8%, 15%) for neck injury. Fifty-one
      percent (43%, 60%) involved patient-handling tasks at the time of incident; 46%
      (37%, 54%) involved inanimate handling. Ninety-one percent (89%, 94%) took sick
      leave, with 52% (43%, 60%) taking > 52 weeks. Only 58% (49%, 65%) returned to
      work. Claimants who had been in communication with employers were significantly
      more likely to return to work than those who did not (chi2 test, p=0.017).
      CONCLUSIONS: Improved management of MH incidents and injured workers are
      recommended.

PMID- 21876272
TI  - Single, childless working women's construction of wellbeing: On balance, being
      dynamic and tensions between them.
AB  - OBJECTIVE: Single, childless working women (SCWW) are a notable proportion of the
      female workforce. The budding research on this population suggests that they have
      issues of wellbeing that may be tied to specific needs of both their workplaces
      and their personal lives, and hence, distinct work-life dynamics that require
      attention. This study explores how SCWW construct their wellbeing. PARTICIPANTS:
      The sample was composed of 22 SCWW aged 29 to 45. METHODS: A discourse analysis
      of the transcripts of semi-structured interviews with these women was performed.
      RESULTS: Most women drew on an interpretative repertoire of "wellbeing as
      balance" (e.g., diversification and reasonable dosing of life's dimensions). It
      was associated with a recurrent subject position we have termed "the dynamic
      woman" whose intensity transfused talk of the activities in her life. Here, work
      becomes a "passion" and a source of appreciated challenges. However, a dilemma
      could arise from these constructions for positioning oneself in relation to the
      cadence of one's active life or rather, in articulating an unambiguous claim to
      balance. Balance/dosing and dynamicity/passion can be uneasy bedfellows.
      CONCLUSIONS: Our analyses raise questions about possible counter[balancing]
      discourses and further argue the relevance of work-life issues for SCWW.

PMID- 21876273
TI  - Pre-placement screenings: An exploratory study of their use in a sample of New
      South Wales workplaces.
AB  - OBJECTIVE: To conduct an exploratory pilot study of pre-placement screening
      practice in Australia by examining the nature and use of pre-placement screenings
      in a sample of New South Wales (NSW) workplaces. PARTICIPANTS: 29 of 279
      employers (10.3%) invited using three sources: a public list of self-insured NSW
      companies, a regional chamber of commerce group and researcher's contacts. The
      majority of respondents (31%) belonged to government administration and
      education. Half of the workplaces employed more than 200 people. METHODS:
      Employers completed an online survey from a link sent by email. RESULTS: Sixteen
      (55%) of the companies had a formal process for conducting pre-placement
      screenings, that were conducted by a range of professionals using a variety of
      methods, with costs ranging from $80 to $350 (Aus). The majority of respondents
      (81%) reported that the pre-placement screenings included an assessment of the
      person's ability to perform the specific physical demands of the job, i.e.
      against the specified physical demands of the position. The majority of employers
      who completed screenings found them useful. CONCLUSIONS: The findings, while from
      a small sample size, provide evidence that pre-placement screenings are being
      conducted in Australian workplaces by various professionals, using varying
      methods and are valued by employers.

PMID- 21876274
TI  - "They want to come to school": Work-based education programs to prevent the
      social exclusion of vulnerable youth.
AB  - OBJECTIVE: This paper describes and compares exemplary work-based education (WBE)
      programs in Ontario Canada designed to meet the needs of two groups of vulnerable
      youth - at-risk youth and youth with severe disabilities. PARTICIPANTS: Two focus
      group interviews were held, one with professionals from exemplary programs
      designed to meet the needs of at-risk youth and one with professionals from
      exemplary programs for youth with severe disabilities. METHOD: Standard
      qualitative analyses were conducted on each focus group transcript to generate
      themes which were subsequently grouped into larger patterns. Then cross-case
      analyses identified consistencies and unique features within the two types of WBE
      programs. RESULTS: Two major patterns that characterize the WBE programs emerged
      from the analyses: the first pattern described the programmatic approaches to WBE
      appropriate for each type of type of student (which included themes such as the
      need for an alternative learning environment for at-risk youth), and the second
      pattern highlighted the rationale for each kind of program (which included themes
      like ensuring equity for youth with severe disabilities). CONCLUSIONS: The
      findings suggest that schools should continue to provide distinct WBE programs
      for each of these groups of vulnerable youth - at-risk youth and youth with
      severe disabilities.

PMID- 21876275
TI  - Industrial workers with occupational hand injury from Tehran factories.
AB  - OBJECTIVE: The aim of this study was evaluation of occupational and non
      occupational risk factors in workers with occupational hand injury. PARTICIPANTS:
      Eighty-two workers with occupational hand injury as cases and 83 controls matched
      for age, gender and also occupation, were included in the study. Controls were
      chosen randomly from the same factories and the same jobs but they did not have
      occupational hand injury. METHODS: The study utilized a case control design for
      analysis. Working circumstances were assessed using a detailed occupational
      questionnaire as well as non-occupational factors. The questionnaire was
      completed for both cases and controls. Multivariate logistic regression modeling
      was used to test the association between occupational and non-occupational
      factors and hand injury. RESULTS: Risk factors for occupational hand injury were:
      rotational shift work, working in the early hours in the morning, working alone;
      and protective factors were: availability of safety equipment or having the
      equipment equipped with safety tools, safety education and using safety
      equipment. Adjusted for confounding factors, protective factors were:
      availability of safety equipment or having the equipment equipped with safety
      tools and the risk factor was working alone. CONCLUSION: Some occupational
      factors are protective and some increase risk for occupational hand injury. By
      modifying these factors we may decrease the prevalence of occupational hand
      injuries.

PMID- 21876276
TI  - Regular physical activity as a basic component of lifestyle modification reduces
      major cardiovascular risk factors among male armored force personnel of Shabestar
      army installation in Iran.
AB  - OBJECTIVES: Cardiovascular/Coronary Heart Disease (CVD) is a leading cause of
      disability and death worldwide. The most important risk factors for CVD are well
      established and are strongly influenced by lifestyle changes. Clearly, physical
      activity has been shown to be extremely important in reducing the burden of this
      disease. The aim of this case-control study was to examine the association
      between intensity of activities and CVD risk factors in healthy military
      personnel. PARTICIPANTS: Two group of subjects (active [engaging in three session
      of field exercises/week] =50, and inactive [with no experience of field
      exercise]=50) were classified by a questionnaire containing demographic, health
      history, type and level of physical activity, and employment information.
      METHODS: Anthropometric indices, lipid-lipoprotein profile, arterial pressures,
      and fasting blood glucose were assessed. Independent sample t-tests were used for
      comparison. RESULTS: Physically active subjects had significantly (p<= 0.05)
      lower measures of body mass indices (except height), lower levels of total
      cholesterol (TC), low density lipoprotein (LDL-C), triglycerides (TG), systolic
      and diastolic blood pressure (S/DBP), risk factor (TC/HDL ratio), atherogenic
      index (LDL/HDL ratio), and higher levels of high density lipoprotein (HDL-C).
      Fasting blood sugar (FBS) was normal in both groups. CONCLUSIONS: To reduce the
      risk factors of developing CVD and preventing its progression significantly, it
      clearly serves to underscore the beneficial properties of physical activity and
      to promote its effectiveness as a support for healthier lifestyles in the
      community and particularly among military personnel. The findings of this study
      substantiate the need for physical exercise to reduce signs and symptoms
      associated with CVD risk, even among a young, healthy, generally active
      population. Further, that these results would appear to corroborate the concept
      of increasing physical activity, including aerobic activity, as a preventative
      measure.

PMID- 21876277
TI  - Evaluation of job stress models for predicting health at work.
AB  - OBJECTIVES: Few workplace health promotion (WHP) interventions are designed to
      improve work conditions. Methods for measurement of work conditions are often
      developed from a risk factor perspective rather than a WHP perspective. More
      knowledge is needed on the work conditions that promote health in order to
      develop a good work environment. The purpose of the present study was to
      investigate if the Demand Control Support model, the Effort Reward Imbalance
      model and the Job Characteristic Inventory are correlated, if the subscales
      predict health and to analyze which combination of subscales is the most useful
      predictor of health longitudinally. PARTICIPANTS: The study used questionnaire
      data from 662 civil servants at baseline and at follow-up 2 years later. METHOD:
      The data were analysed by multiple regressions. RESULTS: A new model; effort,
      reward, and variety, was found having a higher predictive power to predict health
      than the original models. CONCLUSIONS: To promote health at work, social
      relations and health-mediating work conditions are important because these
      conditions may buffer health. Health can be assumed to be a resource that is
      created in everyday activities and interactions in workplaces, and there is a
      need to develop health measure instruments based on holistic health theories.

PMID- 21876278
TI  - Occupational stress and psychosomatic complaints among health professionals in
      Beijing, China.
AB  - OBJECTIVE: To investigate the prevalence, distribution and correlates of
      occupationally-related psychosomatic complaints among a previously understudied
      workforce. PARTICIPANTS: A selection of 336 public health professionals working
      in Beijing, China. METHODS: A self-reporting questionnaire survey was used (99%
      response rate). RESULTS: The incidence of ocular discomfort was relatively high
      for health professionals aged below 60 years, headache or dizziness was mostly
      reported by the older age groups, insomnia or sleep disorders were common among
      those aged 30-39 years, while self-reported depression or emotional instability
      were concentrated in younger staff. Regression analyses revealed that age,
      personal life habits, family status, work conditions and occupational environment
      were related to eye discomfort, headache, dizziness, insomnia, sleep disturbance,
      depression or emotional instability. Moreover, undertaking a busy work schedule
      of long duration and work-induced stress were major correlates for illness and
      other subjective symptoms. On the other hand, having a friendly working
      atmosphere and a high interest in one's work were negatively correlated with
      psychosomatic symptoms. CONCLUSIONS: Overall, our study suggests high-intensity
      work and various other occupational factors may be strongly related to
      psychosomatic symptoms among health professionals in China.

PMID- 21876279
TI  - Changes in gluteal pressure and pelvic inclination angles after continuous cross
      legged sitting.
AB  - OBJECTIVE: The objective of this study was to determine the changes in left and
      right gluteal pressures and posterior inclination angles between the anterior
      superior iliac spine (ASIS) and posterior superior iliac spine (PSIS) on both
      sides after continuous cross-legged sitting. METHODS AND PARTICIPANTS: Fourteen
      young adults (nine males and five females) were recruited. The statistical
      significance of differences in parameters between before and after continuous
      cross-legged sitting was tested by paired t-tests. RESULTS: After sitting in a
      right-crossed-leg position for 10 minutes and then returning to a upright sitting
      posture, the subjects' right gluteal pressure increased significantly compared to
      before cross-legged sitting (p< 0.05). After sitting in a right-crossed-leg
      position and then returning to an upright standing posture, the posterior
      inclination between the right ASIS and PSIS increased significantly compared to
      before cross-legged sitting (p< 0.05). CONCLUSION: These results indicate that
      continuous cross-legged sitting may cause malalignment of the pelvis after the
      cross-legged sitting period.

PMID- 21876280
TI  - An improved half-covered helical cone-beam CT reconstruction algorithm based on
      localized reconstruction filter.
AB  - Traditional helical cone-beam Computed Tomography (CT) is based on the assumption
      that the entire cross-section of the scanned object is covered by x-rays at each
      view angle. Because of the size limitation of planar detector, the traditional
      helical cone-beam CT scanning is restricted when the cross-section of the object
      is larger than the field of view (FOV) of the CT system. The helical cone-beam CT
      scanning based on FOV half-covered can almost double the FOV, whose mechanism is
      simple and the scanning efficiency is the same as that of traditional helical
      cone-beam CT. During reconstruction, the extended helical cone-beam FDK algorithm
      (called half-covered helical FDK for short) is developed, and the computational
      efficiency of this algorithm is high. But the reconstruction image has truncation
      error. Regarding this problem, this paper extends the idea of 2D local
      reconstruction to 3D half-covered helical cone-beam CT, and develops an improved
      half-covered helical cone-beam CT reconstruction algorithm based on localized
      reconstruction filter. Experimental results indicate that the presented algorithm
      well solves the truncation error of the half-covered helical FDK algorithm,
      improves the quality of the reconstruction image. And for the noise projection
      data, the presented algorithm can suppress noise and get better results.
      Moreover, the reconstruction time is much less.

PMID- 21876281
TI  - Application of XANES profiles to X-ray spectromicroscopy for biomedical
      specimens: part II. Mapping oxidation state of cysteine in human hair.
AB  - Human hair fibers are primarily composed of keratin protein, characterized by a
      very high content of cysteine, a sulfur-containing amino acid, which ordinarily
      forms cystine via a disulfide bond. It is known that some cystine residues are
      converted to cysteic acid during permanent waving or hair coloring, although
      details of their distribution and extent are still unclear. In this study, by
      using difference in XANES profiles of cystine and cysteic acid at the S-K
      absorption edge, the formation of cysteic acid was confirmed for homogenized
      samples of permed or bleached hair. Furthermore chemical mapping of cysteic acid
      was performed on hair-section samples with X-ray contact microscopy. The
      peripheral region, cuticle, in bleached hair showed the highest content of
      cysteic acid compared with the other parts, while permed hair showed relatively
      uniform distribution. This finding suggests that perming and bleaching damage
      hair by different mechanisms.

PMID- 21876282
TI  - Correction of image artifacts from treatment couch in cone-beam CT from kV on
      board imaging.
AB  - PURPOSE: To investigate image artifacts caused by a standard treatment couch on
      cone-beam CT (CBCT) images from a kV on-board imager and to develop an algorithm
      based on spatial domain filtering to remove image artifacts in CBCT induced by
      the treatment couch. METHODS: Image artifacts in CBCT induced by the treatment
      couch were quantified by scanning a phantom used to quantify CT image
      performance. This was performed by scanning the phantom setup on a regular
      treatment couch and in air with the kV on-board imager. An algorithm was
      developed to filter image artifacts from the treatment couch by processing of
      cone-beam radiographic projections using two scans: one scan of the phantom and
      treatment couch and a second scan of the treatment couch only. This algorithm is
      based on a pixel-by-pixel removal of beam attenuation due to the treatment couch
      from each projection of the phantom and couch scan. The net couch-filtered
      projections were then used to reconstruct CBCT. RESULTS: We found that the
      treatment couch causes considerable image artifacts: CT number uniformity is
      degraded and varies as much as 15%, and noise in CBCT scans with phantom plus
      couch (3.5%) is higher than for the phantom in air (1.5%). The spatial domain
      filtering technique reduces noise by more than 1.5%, improves uniformity by a
      factor of 2, and removes ringing and streaking artifacts related to the standard
      treatment couch in CBCT reconstructed from couch-filtered projections. This
      filtering technique was tested successfully to filter other hardware objects such
      as a patient immobilization body-fix frame. CONCLUSIONS: The standard treatment
      couch causes image artifact in CBCT from kV on-board imaging systems. The spatial
      domain filtering technique developed in this work improves image quality of CBCT
      by preprocessing the projections prior to CBCT reconstruction. This technique
      might be useful to filter other hardware objects from CBCT which may contribute
      to the degradation of image quality.

PMID- 21876283
TI  - A new 3D information acquisition method of micro-drilling marks on ancient
      perforated stone bead through micro-CT.
AB  - Drilling is one of the most complex techniques for making ancient stone or jade
      implement or adornment. However, related research on ancient stone or jade
      drilling technology lags behind, for there are rare records or discovery of the
      ancient drilling tools. Drilling marks are very useful information for analysis
      and research of the ancient drilling techniques. The traditional information
      acquisition methods are very difficult to apply effectively on smaller
      perforations. In this paper, we introduced a new nondestructive method to solve
      the observation difficulty problem. The ancient bead was scanned by 3D-MUCT
      system. Then through T-FDK algorithm, improved NL-means denoising algorithm and
      high accurate calibration, the 3D geometrical information of micro-drilling marks
      on outer and inner wall of the perforation were reconstructed. The experimental
      results proved that this method can provide key information for the analysis of
      the ancient stone drilling technique and ancient jade authentication.

PMID- 21876284
TI  - An antiproton simulation study using MCNPX for radiation therapy.
AB  - Radiation therapy using antiprotons is a potential interesting future modality.
      Energetic antiprotons penetrate matter with almost near identical stopping powers
      and radio biological effectiveness (RBE) as protons in the region well before the
      Bragg peak region. When the antiprotons come to rest at or near the Bragg peak,
      they annihilate releasing almost 2 GeV per annihilation. Most of the energy is
      carried away on the average by 4 to 5 energetic pi mesons. The annihilations lead
      to roughly a doubling of physical dose with additional increase due to RBE in the
      Bragg peak region. This study was undertaken in order to assess the effect of the
      products of antiproton annihilations on depth dose profiles through MCNPX
      simulations. Beams of protons and antiprotons with varying energies and field
      sizes were used in the simulations. In our study, for 126 MeV beam, the peak to
      entrance (P/E) dose ratios of 4.9 for protons and 8.9 for antiprotons were found
      which gave the antiproton/proton P/E dose ratio equals to 1.8. This is in
      excellent agreement with the previous result obtained with FLUKA simulations.

PMID- 21876285
TI  - A curve-filtered FDK (C-FDK) reconstruction algorithm for circular cone-beam CT.
AB  - Circular cone-beam CT is one of the most popular configurations in both medical
      and industrial applications. The FDK algorithm is the most popular method for
      circular cone-beam CT. However, with increasing cone-angle the cone-beam
      artifacts associated with the FDK algorithm deteriorate because the circular
      trajectory does not satisfy the data sufficiency condition. Along with an
      experimental evaluation and verification, this paper proposed a curve-filtered
      FDK (C-FDK) algorithm. First, cone-parallel projections are rebinned from the
      native cone-beam geometry in two separate directions. C-FDK rebins and filters
      projections along different curves from T-FDK in the centrally virtual detector
      plane. Then, numerical experiments are done to validate the effectiveness of the
      proposed algorithm by comparing with both FDK and T-FDK reconstruction. Without
      any other extra trajectories supplemental to the circular orbit, C-FDK has a
      visible image quality improvement.

PMID- 21876286
TI  - A new CT metal artifacts reduction algorithm based on fractional-order sinogram
      inpainting.
AB  - In this paper, we propose a new metal artifacts reduction algorithm based on
      fractional-order total-variation sinogram inpainting model for X-ray computed
      tomography (CT). The numerical algorithm for our fractional-order framework is
      also analyzed. Simulations show that, both quantitatively and qualitatively, our
      method is superior to conditional interpolation methods and the classic integral
      order total variation model.

PMID- 21876287
TI  - New relationship between the divergent beam projection and the Radon transform.
AB  - In this paper, we present some new relationship between the divergent beam
      projection and the Radon transform. An application of our results is to implement
      the Radon inversion from divergent beam projection.

PMID- 21876288
TI  - Low dose reconstruction algorithm for differential phase contrast imaging.
AB  - Differential phase contrast imaging computed tomography (DPCI-CT) is a novel x
      ray inspection method to reconstruct the distribution of refraction index rather
      than the attenuation coefficient in weakly absorbing samples. In this paper, we
      propose an iterative reconstruction algorithm for DPCI-CT which benefits from the
      new compressed sensing theory. We first realize a differential algebraic
      reconstruction technique (DART) by discretizing the projection process of the
      differential phase contrast imaging into a linear partial derivative matrix. In
      this way the compressed sensing reconstruction problem of DPCI reconstruction can
      be transformed to a resolved problem in the transmission imaging CT. Our
      algorithm has the potential to reconstruct the refraction index distribution of
      the sample from highly undersampled projection data. Thus it can significantly
      reduce the dose and inspection time. The proposed algorithm has been validated by
      numerical simulations and actual experiments.

PMID- 21876289
TI  - Rapid analysis of iron concentrates by x-ray fluorescence spectrometry with sol
      gel sample preparation technology.
AB  - A rapid method for the analysis of iron concentrates by gel sample preparation
      and x-ray fluorescence (XRF) spectrometry detection was developed. The solution
      digested by aqua regia was mixed with agarose, and then agarose was dissolved in
      the boiling solution and the mixture became quasi-solid gel at ambient
      temperature. The quasi-solid gel was detected by XRF. Analytical characteristics
      of the methods used were compared, and their reliability were tested against
      several certified reference materials of iron concentrates. The relative standard
      deviation was less than 0.3%.

PMID- 21876290
TI  - Substance use among persons with traumatic brain injury: a review.
AB  - This paper provides a review of the current literature in the area of substance
      use and traumatic brain injury (TBI). Collectively, these studies demonstrate
      that substance use and SUD are common in the TBI population both pre- and post
      injury, are a frequent causative factor in injury acquisition, complicate the
      rehabilitation process, and have substantial negative impact on individual health
      and well being. Further, individuals with a demonstrated SUD and concurrent TBI
      are likely to be severely limited in their ability to access SUD care due to
      physical barriers. This literature is reviewed and then considered in terms of
      its general weaknesses. Finally, a brief outline of future research needs is
      provided.

PMID- 21876291
TI  - Factors predicting depression among persons with spinal cord injury 1 to 5 years
      post injury.
AB  - OBJECTIVES: Estimate changes in prevalence of Major Depressive Disorder (MDD) 1
      to 5 years post spinal cord injury (SCI); Identify demographic, injury, and
      discharge factors associated with MDD at 1 and 5 years post-injury; Identify
      modifiers of changes in MDD. DESIGN: Retrospective. SETTING: Model Spinal Cord
      Injury System. PARTICIPANTS: 2,256 adult participants enrolled in the National
      Spinal Cord Injury Statistical Center between 1999 and 2004. MAIN OUTCOME
      MEASURE: MDD as determined by the Patient Health Questionnaire-9 (PHQ-9).
      RESULTS: Prevalence of MDD was 11.9% at 1 year and 9.7% at 5 years post SCI. Odds
      of MDD decreased significantly 1 to 5 years post-injury (odds ratio=1.26, 95%
      confidence interval=1.02, 1.56). At 1 year post-injury, the odds of MDD was
      greater for persons 35-55 years old at injury, unemployed, having an indwelling
      catheter or voiding bladder management at discharge, and higher scores on ASIA
      motor index. At 5 years post-injury, the odds of MDD were greater for females,
      persons 35-55 years old at injury, those with a high school education or less,
      those having an indwelling catheter, voiding, and no bladder management at
      discharge, and higher scores on ASIA motor index. Sex was the only significant
      modifier. CONCLUSIONS: MDD occurs commonly 1 to 5 years post SCI.
      Sociodemographic, injury, and discharge factors are associated with the
      development and changes in depression. Future research should expand upon current
      findings in order to identify, prevent, and reduce the prevalence of MDD after
      SCI.

PMID- 21876292
TI  - The effect of robo-horseback riding therapy on spinal alignment and associated
      muscle size in MRI for a child with neuromuscular scoliosis: an experimenter
      blind study.
AB  - PURPOSE: This case study was conducted to highlight the clinical and radiological
      features of a patient with progressive neuromuscular scoliosis before and after
      robo-horseback riding therapy (HBRT). DESIGN: A clinical, laboratory, and
      radiological analysis of a single case. SUBJECT: An 11-year-old child, dignosed
      right thoracolumbar neuromuscular scoliosis secondary to cerebral palsy. METHOD:
      The child received a 5-week course of robo-HBRT, comprising of 60-minute periods
      a day, five times a week. Postural alignment was determined by Cobb's method. A
      real-time magnetic resonance imaging (MRI) was performed to determine the robo
      HBRT-induced changes in cross-sectional area (CSA) of bilateral thoracic (T2) and
      lumbar (L2) paraspinalis. Clinical tests including the standard Gross Motor
      Function Measure (GMFM) and manual muscle testing (MMT) with the Lafayette Manual
      Muscle Tester were used to compare the intervention-related changes in motor
      performance and power. The surface EMG was also used to examine therapy-induced
      changes in muscle activity amplitude for bilateral T2 and L2 paraspinalis and
      rectus abdominis muscles. RESULTS: Clinical motor and strength scores increased
      after the intervention. Radiographic Cobb's angle, MRI, and electromyographic
      amplitude data demonstrated notably enhanced spinal alignment and muscle fiber
      CSA and symmetry, respectively. CONCLUSIONS: This is the first study to provide
      evidence of the therapeutic efficacy of a novel form of robo-HBRT on motor
      function and associated structural and motor control improvements, thus
      suggesting a method of augmenting therapy in neuromuscular scoliosis.

PMID- 21876293
TI  - The effect of combining daily restraint with bimanual intensive therapy in
      children with hemiparetic cerebral palsy: a self-control study.
AB  - AIM: To examine the influence of combining restraint therapy with bimanual
      intensive therapy on the unimanual and bimanual function among children with
      hemiparetic cerebral palsy (CP). Included were nine children (ages 6-9 yr), with
      Manual Ability Classification System scores of 2-3, Gross Motor Functional
      Classification System 1-2; INTERVENTION: 10 days, six hours per day including one
      hour of restraint followed by five hours of bimanual activities. EVALUATIONS: One
      month and immediately prior to the intervention (as the control period),
      immediately, two months and six months post-intervention. The Assisting Hand
      Assessment was the primary outcome measure, along with the Jebsen-Taylor Test of
      Hand Function, the Jamar pinch gauge for grip and pinch, and the Pediatric
      Evaluation of Disability Inventory (PEDI). RESULTS: No significant change was
      observed during the pre-intervention control period in any of the outcome
      measures; a significant improvement in all outcome parameters was noted after the
      intervention as compared to the control period. These achievements were still
      significantly higher than baseline values at six months post-intervention.
      CONCLUSION: Children with hemiparetic CP at this level of impairment might
      benefit from a short daily intervention program of combining restraint with
      bimanual training in order to improve unimanual and bimanual function.

PMID- 21876294
TI  - Electrical stimulation improves gait in children with spastic diplegic cerebral
      palsy.
AB  - BACKGROUND: Electrical stimulation (ES) of proximal muscles during gait training
      has not previously been reported as a management option for improving muscle tone
      and gait in spastic diplegic children. OBJECTIVE: To investigate the effects of
      simultaneous continuous ES of both hip abductors and adductors during walking on
      muscle tone, knee alignment and gait characteristics in children with spastic
      diplegic cerebral palsy (CP). SUBJECT: Three groups of children participated in
      this project: the study group, consisting of 17 ambulant children with spastic
      diplegic CP; a control group of 15 ambulant children with spastic diplegic CP;
      and another control group, with 17 healthy children. METHODS: The study group
      underwent two different ES management programs. The first was a one-time trial
      management program that involved ongoing ES of bilateral hip adductor and
      abductor muscles at the sensory and motor levels, respectively, during walking
      for a predetermined distance. The second ES program lasted for one week and
      involved 15 minutes of ongoing ES of bilateral hip adductor and abductor muscles
      at the sensory and motor levels, respectively, during walking for three sessions
      a day for the week. RESULTS: Marked improvement in gait performance (p < 0.001),
      muscle tone (p < 0.01) and knee position of the study group was observed.
      CONCLUSION: ES to the hip adductor and abductor muscles simultaneously at the
      sensor and motor levels, respectively, improved gait in spastic diplegic CP
      children.

PMID- 21876295
TI  - The effect of variable gait modes on walking parameters among children post
      severe traumatic brain injury and typically developed controls.
AB  - The goal of the present study was to assess the effect of various walking modes
      on dynamic gait characteristics and to evaluate the possible differences in the
      adaptation reactions between children post severe traumatic brain injury (TBI)
      and typically developed (TD) controls. METHODS: Thirteen children post severe
      TBI, mean of 3.5 years post trauma, independent walkers, with a walking velocity
      > 1.1 m/sec, and 15 TD controls participated in this study. Ages were 7-13 years.
      Gait speed, step time and length and step time and length variability were
      assessed by an electronic walkway. The children completed three cycles on the
      walkway for each of the following situations: comfortable walking, walking as
      fast as possible, as slow as possible and walking on a straight line. RESULTS:
      Despite a similar walking performance while walking at a "regular" speed,
      children post severe TBI exhibit a significantly reduced range of walking speeds
      (73-154 cm/sec), about half, as compared to TD children (54-193 cm/sec) across
      the study assignments. In addition, while "walking on a straight line" children
      post TBI walk slower, with increased step variability as compared to their peers.
      CONCLUSION: Children post severe traumatic brain injury may achieve independent
      walking at a comparable rate to typically developed controls; however their
      impairments will be exacerbated as the demands increase. Since a variety of
      walking speeds is crucial for independent daily living at any age and for
      children in particular, and since adequate balance is an inherent element of
      walking, these issues need repeated assessments and the children should receive
      appropriate treatment.

PMID- 21876296
TI  - The effect of a stretching device on hand spasticity in chronic hemiparetic
      stroke patients.
AB  - We attempted to evaluate the effect of a stretching device for treatment of hand
      spasticity in chronic stroke patients. We recruited 21 chronic hemiplegic stroke
      patients with severe finger flexor spasticity and randomly assigned them to the
      intervention group (10 patients) and control group (11 patients). The stretching
      device consisted of a resting hand splint, finger stretcher, and frame. The
      stretching state was maintained for 30 seconds and relaxed for the next 30
      seconds. This stretching and relaxation were repeated for 20 minutes (one
      session). The stretching program was practiced 2 sessions/day and 6 days/week for
      3 weeks for the patients of the intervention group. The effect of this stretching
      device was assessed using the modified Ashworth scale (MAS) score of finger
      flexor muscles. Patients in both groups were assessed six times within an
      interval of one week and patients in the intervention group were assessed two
      times before starting the stretching program. The two-way repeated measures
      analysis of variance (ANOVA) test for evaluation of the effect of intervention
      across all time-points between the two groups showed a significant interaction
      between time and effect of intervention (P < 0.001). Within the intervention
      group, the average of mean MAS score at Pre-1 and Pre-2 were 2.83 and 2.93,
      respectively (the difference between Pre-1 and Pre-2 was not significant (P>
      0.05)), and this improved significantly to 1.97 at Inter-1, 1.55 at Inter-2, 1.20
      at Inter-3, and 1.97 at Post-1 (P < 0.001) using the one-way repeated measures
      ANOVA test for evaluation of the effect of intervention across all time-points.
      We found that our stretching device was effective in relieving hand spasticity in
      chronic stroke patients.

PMID- 21876297
TI  - Efficacy of therapeutic ultrasound in the treatment of spasticity: a randomized
      controlled study.
AB  - The purpose of this study was to investigate the effect of ultrasound (US) on the
      spasticity occurring in the ankle plantar flexor muscles after a cerebrovascular
      event. According to the modified Ashworth scale (MAS), the hemiplegic patients
      with stage 2-3 spasticity on the ankle plantar flexor muscles were enrolled in
      the study and divided into two groups. Passive stretching exercise was applied to
      both groups. Additionally, 10-minute US was applied to one of the groups, using
      the mode of continuous wave of 1.5w/cm<formula>^{2}</formula> to the calf muscles
      before stretching. In order to monitor the efficacy of the treatment in the
      patients, MAS, Hmax/Mmax ratio, the ankle range of motion (ROM), Functional
      Independence Measure and Brunnstrom Motor Recovery Stage were evaluated. While a
      significant recovery was monitored in the MAS and ankle ROM measurements after
      treatment in both groups, no change was obtained in the other parameters. No
      significant difference was detected in any of the measurements between the
      groups. In this study, US treatment applied in combination with the ankle plantar
      flexor muscles passive stretching exercise was determined to have no effect on
      the stretching treatment in minimizing the spasticity.

PMID- 21876298
TI  - Assisted leg displacements and progressive loading by a tilt table combined with
      FES promote gait recovery in acute stroke.
AB  - OBJECTIVE: Here we developed and tested a novel system for early motor
      rehabilitation in acute stroke when patients are unable to stand and walk without
      assistance. Stepping performance may be largely facilitated by providing
      treatment in the supine position on a tilt table using step-synchronized
      functional electrical stimulation (FES) with assisted leg movements and
      progressive limb loading. METHODS: Sixty-one individuals with acute stroke were
      randomly assigned to two groups, experimental and control. The first group
      received both a conventional therapy and FES-therapy combined with progressive
      limb loading, whereas the control group received a conventional therapy only.
      Changes after treatment were assessed using clinical scores and
      neurophysiological measurements of movement performance. RESULTS: After
      treatment, there was an improvement of the clinical scores, muscle forces and
      everyday life activity performance in both groups, however, significantly higher
      in the experimental group. Active rhythmic movements of the non paretic leg often
      provoked muscle activity in the paretic leg as well as there was a reduction of
      the contralateral leg muscle contraction during paretic leg movements.
      CONCLUSION: The developed FES and leg displacement-assisted therapy facilitates a
      smooth transition to walking in the vertical position and increases the patient's
      functional abilities and the effectiveness of rehabilitation.

PMID- 21876299
TI  - Acute effects of locomotor training on neuromuscular and metabolic profile after
      incomplete spinal cord injury.
AB  - OBJECTIVES: Locomotor training (LT) enhances walking in individuals with spinal
      cord injuries (SCIs). We tested the acute effects of 4 days of LT using BWSTT
      combined with Robotic Locomotor therapy compared to BWSTT twice weekly. DESIGN:
      Two non-ambulatory participants with an American Spinal Injury Association
      Impairment Scale (AIS) D. Both received LT for 2 weeks as a portion of their
      clinical inpatient rehabilitation program and both used wheelchairs as their
      primary method of mobility. Over a 2 week period, one participant received a
      total of 8 visits consisting of manual BWSTT (twice weekly) combined with Robotic
      locomotor therapy (twice weekly). The other participant preformed manual BWSTT
      (twice weekly) for a total of 4 visits. Resting energy expenditure, body
      composition, muscle strength, submaximal oxygen consumption (VO2) and blood
      lactate during LT were measured pre and post-training. RESULTS: The average
      maximum voluntary contraction of both knee extensor muscle groups increased by 28
      34% with associated reduction in spasticity to the BWSTT participant. Two week
      interventions resulted in a downward shift of the lactate concentrations for both
      participants, increase in resting energy expenditure and shift in substrate
      utilization. DISCUSSION AND CONCLUSION: A clinical paradigm of incorporating
      BWSTT with robotic locomotor therapy for 4 days/ week did not provide additional
      physiological benefits to skeletal muscle strength, spasticity or metabolic
      profile compared to twice weekly of LT using BWSTT.

PMID- 21876300
TI  - Prognostic factors for motor outcome in patients with compressed corticospinal
      tract by intracerebral hematoma.
AB  - Little is known about prognostic factors associated with motor outcome when the
      corticospinal tract (CST) was compressed by hematoma. Using diffusion tensor
      tractography (DTT), we attempted to investigate prognostic factors for motor
      outcome in patients whose affected CST was compressed by hematoma. The study
      included 51 consecutive severe hemiparetic patients with a hematoma involving the
      corona radiata and basal ganglia. Integrities of the affected CSTs were preserved
      to the cerebral cortex and were found to be compressed by a hematoma on DTT.
      Patients were classified into four groups according to the region which the CST
      was originated from the precentral gyrus (type A), postcentral gyrus (type B),
      posterior parietal cortex (type C), and premotor cortex (type D). We measured the
      ratios of DTT parameters between affected/unaffected hemispheres.The motor
      function of the affected extremities at 6-month after onset was better with the
      following order: DTT type A, type B, type C, and type D patients. The 6-month
      motor function for DTT type A patients was higher than that of DTT type D
      patients (p=0.008). The fractional anisotropy ratio between the affected and
      unaffected CST was positively correlated with the 6-month motor function of the
      affected extremities (Pearson's correlation coefficient, p=0.025, r=0.313). We
      found that motor outcome differed according to the originated area of the
      affected CST and the degree of injury of the affected CST in patients whose
      affected CST was compressed by hematoma.

PMID- 21876301
TI  - Comparing routine neurorehabilitation programme with callisthenic exercises in
      multiple sclerosis.
AB  - We conducted a study that examined the effectiveness of callisthenic exercises in
      multiple sclerosis. 30 individuals were divided into two groups. The first group
      did 15~callisthenic exercises and the second group did routine
      neurorehabilitation programme. Both groups did the programmes for three days per
      week over six weeks. Visual Analogue Scale for Fatigue (VAS-F), muscle strength
      tests, Berg Balance Scale (BBS), Multiple Sclerosis Functional Composite (MSFC),
      Turkish versions of Short Form of 36 (SF-36), and Hospital Anxiety and Depression
      Scale (HAD) were used for evaluation. After physiotherapy programmes VAS-F,
      muscle strength, BBS scores decreased significantly in both groups. HAD anxiety
      score of the first group and HAD depression score of the second group changed
      significantly. There were no differences in MSFC and SF-36 scores in any groups.
      The difference between groups was not significant in any parameters, except for
      the muscle test for upper limbs of the second group. Callisthenic exercises are
      seen as a new therapy choice, which are different from routine exercises, in
      order to decrease fatigue, improve balance and muscle strength. Callisthenics are
      thought to be a beneficial tool for MS patients.

PMID- 21876302
TI  - ICF use to identify common problems on a TBI neurorehabilitation unit in Spain.
AB  - OBJECTIVE: To describe functioning and health of individuals with traumatic brain
      injury (TBI) based on the International Classification of Functioning, Disability
      and Health (ICF). METHODS: A cross-sectional, prospective study was conducted in
      a neurorehabilitation hospital. Data collection included socio-demographic
      factors, single interviews based on the extended ICF Checklist 2.1 for TBI,
      patient ratings on general health and functioning status, WHOQoL, EQ5D and the
      Comorbidity Questionnaire. RESULTS: 103 patients (81%males) were included in the
      study. The mean of age was 34 yrs. 24% were inpatients whereas 76% were
      outpatients. 130 out of 150 categories (87%) of the extended checklist were
      relevant in > 10% of patients. Differences in functioning and disability between
      patients in the shorter versus long term situation were noted to be predominantly
      in the ICF domains of Activities and Participation as well as in Body Functions.
      Correlations between EQ5D and ICF-based data collections were all p < 0.01.
      CONCLUSIONS: This study identified the most common problems in patients with TBI
      receiving Neurorehabilitation services based on the ICF. Results emphasize the
      need to describe disability and rehabilitation standards from a comprehensive
      perspective that not only includes Body Functions and Structures but also the ICF
      domains of Activities and Participation and Environmental factors.

PMID- 21876303
TI  - Diffusion tensor imaging findings in neurologically asymptomatic patients with
      end stage renal disease.
AB  - Various neurological problems of the brain are known to occur in patients with
      end stage renal disease (ESRD). However, little is known about diffusion tensor
      imaging (DTI) findings in patients with ESRD. Using DTI, we attempted to
      investigate DTI findings in patients with ESRD who showed no specific lesions on
      conventional brain MRI. We recruited 10 consecutive patients with ESRD for whom
      at least 3 years had passed since the start of peritoneal dialysis and who showed
      no neurological abnormality on neurologic examination. We excluded 6 patients who
      showed cerebral infarct (4 patients) and diabetes mellitus with peripheral
      neuropathy (2 patients); finally, 4 patients (39.75 +/- 9.84 years) were included
      in this study. We evaluated hand motor function and cognition. DTI data were
      acquired using a 1.5-T Philips Gyroscan Intera system and diffusion tensor
      tractographies (DTTs) for five neural tracts (corticospinal tract, fornix,
      superior longitudinal fasciculus, inferior longitudinal fasciculus, and inferior
      fronto-occipital fasciculus) were evaluated. With the exception of 1 patient who
      revealed a mild abnormality at a higher cognitive function, no abnormalities in
      motor and cognitive function were observed. Among the 10 DTTs, except for those
      of the corticospinal tract, all 4 patients had more than one lesion. Patients
      with ESRD showed abnormalities on DTTs that were associated with cognition;
      however, they did not show significant cognitive abnormalities.

PMID- 21876304
TI  - Vascular calcification in chronic kidney disease: mechanisms and clinical
      implications.
AB  - Vascular calcification is a well-known complication of chronic kidney disease and
      one of the main predictors for increased cardiovascular morbidity and mortality
      in these patients. It may happen in 2 main types of intimal calcification, as a
      part of diffuse atherosclerosis, and medial calcification, which is generally
      focal in distribution, unrelated to atherosclerotic risk factors, and seen in
      younger hemodialysis patients. Pathogenesis may be genetic, mineral metabolism
      related, or nonmineral metabolism related. Increased calcium, phosphorus, and
      calcium- phosphorus product; decreased parathyroid hormone level; and overzealous
      use of active vitamin D supplements are the main mineral metabolism-related
      mechanisms of vascular calcification. Other mechanisms are formation of matrix
      vesicles and cellular apoptosis, with generation of hydroxyapatite crystals
      within vesicles and apoptotic bodies. The interplay of various activator proteins
      of vascular calcification such as bone morphogenetic proteins and receptor
      activator of nuclear factor-kappa B ligand, or inhibitor proteins like matrix Gla
      protein, bone morphogenetic protein-7, osteopontin, osteoprotegerin, fetuin-A,
      Smad6, and pyrophosphate are important in establishment of vascular
      calcification. Vascular calcification is related to all-cause and cardiovascular
      mortality both in general population and dialysis patients. Minimizing
      traditional risk factors of vascular calcification, prevention of hypercalcemia,
      and avoidance of high doses of calcium-based phosphate binders and vitamin D
      analogues are important measures for prevention or attenuation of progression of
      vascular calcification. Sevelamer and cinacalcet may prevent progression of
      vascular calcification. With the evolving knowledge of the pathogenesis of
      vascular calcification, we can look forward to emergence of novel therapies for
      this complication in the future.

PMID- 21876305
TI  - A critical review of the works of pioneer physicians on kidney diseases in
      ancient Iran: Avicenna, Rhazes, Al-akhawayni, and Jorjani.
AB  - The history of kidney and urologic disorders dates back to the dawn of
      civilization. Throughout history of medicine, urine, the first bodily fluid to be
      examined, has continuously been studied as a means of understanding inner bodily
      function. The purpose of this review was to appraise the contributions of the
      ancient Iranian physician pioneers in the field of kidney and urological
      disorders, and to compare their beliefs and clinical methods with the modern
      medicine. We searched all available reliable electronic and published sources for
      the views of ancient Iranian physicians, Avicenna, Rhazes, Al-Akhawayni, and
      Jorjani, and compared them with recent medical literature. Our findings showed
      that ancient Iranian physicians described the symptoms, signs, and treatment of
      kidney and urological disorders; addressed bladder anatomy and physiology; and
      performed bladder catheterization and stone removal procedures in accordance with
      contemporary medicine. Ancient Iranian physicians pursued a comprehensive
      scientific methodology based on experiment, which is in compliance with the bases
      of modern medicine.

PMID- 21876306
TI  - Pediatric urolithiasis: an experience of a single center.
AB  - INTRODUCTION: The aim of this study was to evaluate the clinical features and
      metabolic and anatomic risk factors of urolithiasis in children. MATERIALS AND
      METHODS: Between 2004 and 2009, a total of 84 children (35 girls and 49 boys) had
      been treated because of urolithiasis. Clinical presentation, urinary tract
      infection, calculus localization, family history, presence of anatomic
      abnormalities, and urinary metabolic risk factors were evaluated,
      retrospectively. RESULTS: The children were between 6 months and 16 years of age
      (mean age, 5.25 +/- 3.61 years). The calculus diameter was 3.2 mm to 31 mm (mean,
      7.31 +/- 4.64 mm). In 90.6% of the cases, the calculus was located only in the
      kidneys and in 2.4% it was only in the bladder. The most common presentations
      were urinary tract infection, restlessness, and abdominal pain. A positive family
      history of urinary calculi was detected in 27.3%; urinary tract infection, in
      23.8%; and anatomic abnormality, in 10.7% of the patients. Metabolic evaluation,
      which was carried out in 78 patients, revealed that 52.6% of them had a metabolic
      risk factor including normocalcemic hypercalciuria (21.7%), hyperuricosuria
      (11.5%), cystinuria (3.8%), and hyperoxaluria (5.1%). CONCLUSIONS: We think that
      urolithiasis remains a serious problem in children in our country. Family history
      of urolithiasis, urologic abnormalities, especially under the age of 5 years,
      metabolic disorders, and urinary tract infections tend to be associated with
      childhood urolithiasis.

PMID- 21876307
TI  - Role of electron microscopy in evaluation of native kidney biopsy: a
      retrospective study of 273 cases.
AB  - INTRODUCTION: Electron microscopy (EM) has been widely utilized in the evaluation
      of kidney biopsies. However, few recent reports have critically assessed its
      diagnostic value. The aim of this study is to assess the role and value of EM in
      the evaluation of native kidney biopsies at our institution. MATERIALS AND
      METHODS: A retrospective evaluation of 273 native kidney biopsies performed at
      our institution over 7 years was done by 2 renal pathologists in order to assess
      the contribution of EM to the final diagnosis in the knowledge of the light
      microscopy and immunofluorescence findings. RESULTS: Electron microscopy had an
      important diagnostic contribution in 39% of cases, in 17% of which EM was
      essential for diagnosis. Electron microscopy was essential in the diagnosis of
      minimal change disease, hereditary nephritis, fibrillary glomerulonephritis, and
      certain classes of lupus nephritis. CONCLUSIONS: In a great percentage of kidney
      biopsies, it was possible to make the diagnosis with certainty based on light
      microscopy and immunofluorescence findings alone. However, still there are
      numbers of cases in which EM is essentially needed to reach definitive diagnosis.
      Therefore, at least a piece of tissue should be kept for EM in appropriate
      fixative in each case, which could then be performed at the discretion of the
      pathologist.

PMID- 21876308
TI  - Role of vitamin A in preventing renal scarring after acute pyelonephritis.
AB  - INTRODUCTION: The role of vitamin A in re-epithelialization of the damaged
      mucosal surfaces has been documented. The aim of this study was to evaluate the
      role of vitamin A in preventing renal scaring after acute pyelonephritis in
      children. MATERIALS AND METHODS: This clinical trial study was conducted in
      children with acute pyelonephritis in Mofid Children Hospital (Tehran, Iran).
      Patients were randomly divided into two groups to receive ceftriaxone and vitamin
      A or ceftriaxone only. Dimercaptosuccinic acid (DMSA) renal scintigraphy was
      performed before the start of the treatment and 6 months later. Results were
      compared for renal scaring between the two groups. RESULTS: Seventy-six patients
      (11 boys and 65 girls) were enrolled. The mean age was 25 +/- 24 months and 54
      patients (71.1%) were under 2 years old. The average vitamin A level was 71 +/-
      24 microg/dL in the treatment group and it was 62 +/- 18 ug/dL in the control
      group. Baseline DMSA scans were comparable between the two groups in terms of
      scarring (P = .53), but the second DMSA scans showed a significant change in
      progression of the renal injury and scaring in the control group compared to
      those treated with vitamin A as well as antibiotic (P < .001). CONCLUSIONS: We
      found administration of the vitamin A was useful in decreasing the amount of the
      injury and scarring following the pyelonephritis. Based on our study, vitamin A
      can be used in conjunction with other treatments in the management of acute
      pyelonephritis in children.

PMID- 21876309
TI  - Hypertension and microalbuminuria 5 years after pregnancies complicated by pre
      eclampsia.
AB  - INTRODUCTION: Pre-eclampsia is part of a spectrum of conditions known as the
      hypertensive disorders of pregnancy. It is claimed that pregnant women with pre
      eclampsia or eclampsia are at increased risk of kidney disease and hypertension
      later in life. We investigated whether Iranian women with a history of pre
      eclampsia had higher rates of hypertension and microalbuminuria compared with
      women with uneventful pregnancy. MATERIALS AND METHODS: Medical records of
      pregnancies delivered at two hospitals in Ahvaz, between March 2001 and February
      2003 were reviewed. Thirty-five pre-eclamptic women were identified and contacted
      for assessment of hypertension and albuminuria. They were compared with 35 women
      matched for year of delivery and age who had a pregnancy uncomplicated by
      hypertension. RESULTS: The mean follow-up from the index pregnancy was 5.7 years
      (range, 5.2 to 7.3 years). While only 1 woman (2.9%) in the control group was
      currently hypertensive, 28.6% of those with a history of pre-eclampsia (n = 10)
      were hypertensive (P = .003; relative risk, 10.0; 95% confidence interval, 1.35
      to 74.00), 7 of whom were receiving antihypertensive medication at the time of
      evaluation. Among the formerly pre-eclamptic women, 7 had albuminuria (20.0%),
      whereas none of the controls were albuminuric (P < .001). Microalbuminuria was
      present in all hypertensive women in the pre-eclampsia group, but not in the only
      women in the control group with hypertension. CONCLUSIONS: We showed that in
      patients with a history of pre-eclampsia, there are increased risks of
      hypertension and microalbuminuria in the long term after pregnancy.

PMID- 21876310
TI  - Cloxacillin as an antibiotic lock solution for prevention of catheter-associated
      infection.
AB  - INTRODUCTION: Catheter-related infection is associated with increased all-cause
      mortality and morbidity in hemodialysis patients. This study aimed to evaluate an
      antimicrobial lock solution (cloxacillin and heparin) in temporary noncuffed
      double-lumen catheters for long-term intermittent hemodialysis as a method of
      preventing catheter-related infection. MATERIALS AND METHODS: Patients on
      hemodialysis with noncuffed temporary double lumen catheter were randomly divided
      into 2 groups. Fifty patients received a solution containing cloxacillin, 100
      mg/mL, plus heparin, 1000 IU/mL as a 2.5-mL solution instilled in each of
      catheter lumens after dialysis session. Another 50 patients received only
      heparin. They were allowed to dwell until the next session of dialysis. RESULTS:
      One catheter-related bacteremia was observed in the antibiotic group whereas
      catheter-related bacteremia was observed in 8 of those who received heparin only.
      The rate of catheter-related bacteremia episodes were 0.5 per 1000 catheter-days
      in the antibiotic group versus 7.8 per 1000 catheter-days in the control group (P
      = .02). CONCLUSIONS: In the present study, application of cloxacillin as
      antibiotic lock solution for dialysis catheters resulted in a considerable
      reduction in catheter-related bacteremia rate.

PMID- 21876311
TI  - Epidemiology of culture-negative peritonitis in Iranian patients on continuous
      ambulatory peritoneal dialysis.
AB  - INTRODUCTION: Culture-negative peritonitis is a major challenge in the treatment
      of peritonitis in continuous ambulatory peritoneal dialysis (CAPD). This study
      aimed to evaluate the culture-negative peritonitis in patients from the Iranian
      CAPD Registry. MATERIALS AND METHODS: Data of 1472 patients from 26 CAPD centers
      were analysed. Peritonitis was defined as any clinical suspicion together with
      peritoneal leukocyte count of 100/mL and more. RESULTS: The patients had been on
      PD for a mean of 500 +/- 402 days. There were a total of 660 episodes of
      peritonitis observed among 299 patients (peritonitis rate of 1 episode in 34.1
      patient-months). Excluding patients with both negative and positive culture
      results, there were 391 episodes of peritonitis in 220 patients (174 culture
      positive episodes in 97 patients and 217 culture-negative episodes in 123). The 1
      to 4-year patient survival rates were 85%, 75%, 69%, and 59% for the patients
      with culture-positive peritonitis, and 92%, 78%, 73% and 63% for the patients
      with culture-negative peritonitis, respectively (P = .34). The technique survival
      rates were 90%, 57%, 42%, and 27% and 95%, 85%, 74%, and 40%, respectively (P =
      .001). On follow-up, there were higher rates of active PD patients, lower rates
      of PD dropouts, and higher rates of kidney transplantation in patients with
      culture-negative peritonitis compared to those with culture-positive peritonitis.
      CONCLUSIONS: In our patients, the prevalence of culture-negative peritonitis was
      high (55.9%). Patient survival with culture-negative peritonitis was comparable
      to those with culture-positive peritonitis and technique survival was higher
      among those with culture-negative peritonitis.

PMID- 21876312
TI  - Effect of adding levamisole on seroconversion response to hepatitis B virus
      vaccination in hemodialysis patients: a single-center experience.
AB  - INTRODUCTION: Hepatitis B virus (HBV) infection is much more common in
      hemodialysis patients than the general population. Up to half of hemodialysis
      patients do not have adequate protective HBV antibodies after HBV vaccination. We
      studied the effects of adding levamisole, as an immunomodulator and adjuvant
      agent, on seroconversion response to HBV vaccination in hemodialysis patients.
      MATERIALS AND METHODS: Thirty-six hemodialysis patients were divided into 2
      groups. The first group received 40 microg of HBV vaccine intramuscularly at 0,
      1, and 6 months plus 100 mg of oral levamisole per day for 12 days. The second
      group received the same amount and method of vaccine and placebo. Serum antibody
      levels were measured in each group after 0, 2, and 4 months after the last dose
      of vaccination. RESULTS: Anti-HBV antibody level in the patients who received
      levamisole was lower than that in the control group. Antibody levels in the
      levamisole group at 0, 2, and 4 months after the last dose of vaccination were
      44.4%, 77.8%, and 77.7%, respectively. In the control group, response rates at 0,
      2, and 4 months were 55.6%, 72.2%, and 77.8% respectively (P = .04, P = .12, and
      P = .08, respectively). CONCLUSIONS: Anti-HBV antibody level was significantly
      lower immediately after HBV vaccination when it was accompanied by levamisole
      administration. However, no significant differences were observed between the two
      groups at 2 and 4 months. Further evaluation is recommended to assess the effect
      of adding levamisole on Hepatitis B surface antibody titer in hemodialysis
      patients.

PMID- 21876314
TI  - An unusual presentation of antineutrophil cytoplasmic antibody-associated
      vasculitis: discrepancy between histopathology and clinical presentation.
AB  - A 60-year-old man was admitted to our clinic with dyspnea, hemoptesis, anuria,
      nephritic syndrome, and a positive myeloperoxidase antineutrophil cytoplasmic
      antibody titer. He was diagnosed with antineutrophil cytoplasmic antibody
      associated vasculitis due to Wegener granulomatosis, microscopic polyangiitis, or
      drug induction. Unexpectedly, histopathologic examination of the kidney biopsy
      specimen revealed the diagnosis of noncrescentic and nonnecrotizing
      glomerulonephritis. We report this case because of the unusual histologic type of
      renal involvement.

PMID- 21876313
TI  - Alteration of panel-reactive antibodies following treatment with either
      atorvastatin or low-dose mycophenolate mofetil in sensitized hemodialysis
      patients.
AB  - INTRODUCTION: Both atorvastatin and mycophenolate mofetil (MMF) have been used
      for panel reactive antibodies (PRA) reduction in transplant candidates. The
      purpose of this study was to compare the effect of low-dose MMF and atorvastatin
      on PRA in sensitized hemodialysis patients waiting for kidney transplantation.
      MATERIALS AND METHODS: A total of 40 adult patients with end-stage renal disease
      who were highly sensitized to human leukocyte antigens (PRA > 40%) were enrolled
      and randomly assigned into atorvastatin or low-dose MMF groups. All of the
      patients received the treatments for 2 months. The PRA status was determined at
      the end of the 1st and 2nd month. RESULTS: Forty percent of the patients in the
      atorvastatin group compared with 5% in the low-dose MMF group showed complete
      response, defined as a minimum 50% reduction in PRA (P = .02). Reduction of PRA
      in the atorvastatin group was significantly higher than that in the low-dose MMF
      group (P = .01). No major infectious or other complications occurred in our
      patients. CONCLUSIONS: Atorvastatin has a significant effect on lowering of PRA
      in sensitized hemodialysis patients waiting for kidney transplantation. In
      addition, a short course of low-dose MMF is safe in ESRD patients; however, it
      has no effect on reduction of PRA.

PMID- 21876315
TI  - Sirolimus-based immunosuppression for treatment of cutaneous warts in kidney
      transplant recipients.
AB  - Dermatological complications, especially skin infections, are very common
      following organ transplantation, and result in a lot of distress in the
      recipient. Herpes zoster, herpes simplex, and human papillomavirus infections are
      common infections in kidney transplant recipients, and therapeutic management is
      usually disappointing in immunosuppression state. We report here 2 cases of
      kidney transplant recipients who developed diffuse human papillomavirus-induced
      cutaneous warts with no response to conventional treatments. According to similar
      reports in organ transplant recipients, we modified the immunosuppressive regimen
      by converting to sirolimus, which led to a rapid relief from cutaneous warts in
      both patients. This evidence along with other case reports suggest that
      conversion to sirolimus may be considered as an effective strategy in cases of
      giant or multiple viral warts in kidney and perhaps other transplant recipients.

PMID- 21876318
TI  - Laparoendoscopic single-site renal cyst marsupialization using a homemade single
      port device has a role as a feasible treatment option.
AB  - AIM: In patients with a renal cyst and concurrent symptoms, we examined the
      effectiveness and safety of laparoendoscopic single-site surgery (LESS) for renal
      cyst marsupialization using a homemade single-port device (HSPD) by a single
      surgeon (S.W.L.). PATIENTS AND METHODS: The present study was conducted on a
      total of 31 patients with a renal cyst. A LESS renal cyst marsupialization was
      performed using a HSPD based on the Alexis(r) wound retractor and a powder-free
      surgical glove. In our study, the mean age was 55.29 +/- 10.86 (range 31-73)
      years and the mean size of the renal cyst was 6.83 +/- 1.09 cm. RESULTS: All the
      surgical procedures were successfully performed. The mean operative time was
      101.35 +/- 16.04 min. Of the patients who underwent the procedure, none presented
      with major complications. In 7 patients who had pain preoperatively, there was a
      significant difference in the visual analogue pain scale score at 6.86 +/- 0.69
      preoperatively and 1.71 +/- 0.49 at postoperative week 4 (p < 0.001). The number
      of patients who were satisfied with the postoperative outcome was 29 (93.5%).
      CONCLUSIONS: In patients with a simple renal cyst, LESS renal cyst
      marsupialization using a HSPD might be considered as a feasible, safe surgical
      treatment option.

PMID- 21876319
TI  - Intra-abdominal fat in children.

PMID- 21876320
TI  - The usefulness of vibration perception threshold as a significant indicator for
      erectile dysfunction in patients with diabetes mellitus at a primary diabetes
      mellitus clinic.
AB  - INTRODUCTION: The aim of this study is to clarify the relationship of erectile
      dysfunction (ED) and diabetes mellitus (DM) parameters (referred to with '1'),
      including peripheral neuropathy (referred to with '2'). METHODS: (1) The DM
      parameters including age, serum levels of blood sugar, hemoglobin A1c, duration
      of DM and number of DM complications were obtained from 145 patients at a general
      DM clinic. (2) The peripheral neuropathy examinations by vibration perception
      threshold (VPT) and Achilles tendon reflex were performed in 97 DM patients.
      Erectile functions in DM patients were evaluated by the International Index of
      Erectile Function (IIEF 5). The DM patients' parameters were compared with the
      IIEF 5 scores. RESULTS: (1) The data showed IIEF 5 scores were significantly
      correlated with patient age, duration of DM and number of DM complications. (2)
      IIEF 5 scores were significantly correlated with VPT time. Furthermore, multiple
      regression analysis revealed that patient age and VPT time were independent risk
      factors for predicting ED in DM patients. CONCLUSIONS: The severity of ED in DM
      patients depended on age, duration of DM, number of DM complications and VPT.
      Significantly, the age of DM patients and the measurement of VPT are considered
      to be simple and useful indicators to diagnose ED in DM patients.

PMID- 21876321
TI  - Feasibility of tri-weekly docetaxel-based chemotherapy for elderly patients (age
      75 and older) with castration-resistant prostate cancer.
AB  - OBJECTIVES: To evaluate the efficacy and safety of docetaxel-based chemotherapy
      for elderly metastatic castration-resistant prostate cancer (CRPC) patients aged
      75 or higher. METHODS: Twenty CRPC patients aged 75 or higher (older group) and
      31 CRPC patients younger than 75 years (younger group) were treated by a regimen
      of docetaxel (70 mg/m(2)) once every 3 weeks. Adjustment for docetaxel dosage and
      period per cycle was subject to investigator's judgment. RESULTS: The median
      relative dose intensity of both groups was 0.84, while the median dose intensity
      and the number of treatment cycles of the younger and older groups were 14.6
      versus 12.3 mg/m(2)/week (p = 0.021), and 9 versus 8 cycles (p = 0.15),
      respectively. In the older group, PSA response rate was 50%, median time to
      biochemical progression was 7.5 months, and median survival time was 15.5 months,
      without any significant difference compared to those of the younger group. No
      significant difference in the incidence of grade 3-4 adverse events was noted
      between both groups. All these parameters for efficacy are comparable to those
      reported for tri-weekly docetaxel regimen. CONCLUSIONS: Tri-weekly treatment by
      docetaxel (70 mg/m(2)) with proper adjustment might contribute to maintaining
      efficacy and safety of the treatment for elderly CRPC patients.

PMID- 21876322
TI  - A new technique for retrograde flexible ureteroscopy after Cohen cross-trigonal
      ureteral reimplantation.
AB  - PURPOSE: Retrograde ureteral access after cross-trigonal ureteral reimplantation
      can be challenging. We present our experience with retrograde ureteral
      catheterization and flexible ureteroscopy after Cohen cross-trigonal
      reimplantation in patients presenting with ureteral stones. MATERIALS AND
      METHODS: Cystoscopy is performed and a Tiemann ureteral catheter is inserted into
      the involved ureteral orifice. A retrograde ureterography is performed and
      hydrophilic guide wire is passed up to the kidney. A dual-lumen ureteral access
      sheath is then passed under x-ray control underneath the ureteral stone. The
      flexible ureterorenoscope is passed under x-ray control up to the stone which is
      then fragmented with a holmium laser. RESULTS: From June 2006 to June 2010, this
      technique was successful in 8 patients without acute or delayed sequelae.
      CONCLUSIONS: Where the endourological expertise is readily available, the ureter
      can be accessed retrogradely even after Cohen cross-trigonal ureteral
      reimplantation in a safe, straightforward and effective modality.

PMID- 21876323
TI  - An autoradiographic study on the pathogenesis of levodopa-induced dyskinesia:
      regulation of dopamine transporter by levodopa in a rat model of Parkinson's
      disease.
AB  - BACKGROUND: The development of abnormal involuntary movements or dyskinesia is a
      serious complication of L-3,4-dihydroxyphenylalanine (L-DOPA) therapy for
      Parkinson's disease (PD). OBJECTIVE: To evaluate the correlation between dopamine
      transporter (DAT) regulated by L-DOPA and the pathogenesis of dyskinesia in PD
      rats. METHODS: Thirty rats were used to establish the PD model by injecting 6
      hydroxydopamine into the right medial forebrain bundle. The sham surgery rats (n
      = 4) received 4 MUl of physiological saline. Then, 19 rats in which PD has been
      successfully induced were randomly assigned to the L-DOPA (20 mg/kg/day; n = 15)
      or model (saline; n = 4) group. After 4 weeks of treatment, (131)I-N-(3
      fluoropropyl)-2beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane was injected
      into the rats, and images of DAT in the brain were acquired using a storage
      phosphor plate. The levels of DAT-specific radioactivity uptake in the bilateral
      corpora striata (left/right) were compared. RESULTS: There was no difference in
      DAT-specific radioactivity uptake between the bilateral corpora striata in the
      sham surgery rats. The images were clear and symmetrically distributed in the
      corpora striata. In PD model rats, the DAT-specific radioactivity uptake
      decreased on the lesioned side and the ratios of uptake between the corpora
      striata were increased. Accumulation of the radioligand on the lesioned side was
      sparse. In the L-DOPA group, the average ratio values were significantly
      increased in dyskinetic rats and reduced in nondyskinetic rats. In addition, the
      differences between the bilateral corpora striata were reduced in nondyskinetic
      rats. CONCLUSION: L-DOPA was shown to downregulate DAT in some PD model rats.
      That process may be involved in the pathogenesis of dyskinesia.

PMID- 21876325
TI  - Toll-like receptor 9 is a novel biomarker for esophageal squamous cell dysplasia
      and squamous cell carcinoma progression.
AB  - BACKGROUND: Stimulation of Toll-like receptor 9 (TLR9) has been linked to
      invasion in various cancer cells in vitro. We investigated TLR9 expression in
      normal, dysplastic and malignant esophageal squamous epithelium. METHODS: TLR9
      expression was analyzed by immunohistochemistry in 46 cases of esophageal
      squamous cell carcinoma, including 12 cases with adjacent squamous dysplasia and
      24 cases with normal esophageal epithelium. TLR9 expression was compared with
      tumor grade, stage, proliferation, apoptosis and vascular density. RESULTS: In
      normal esophageal squamous epithelium, TLR9 staining intensity decreased linearly
      from the basal layers to the superficial layers (p < 0.001). Strong TLR9
      expression was detected across full thickness of high-grade dysplasia, the
      intensity clearly differing from the normal squamous epithelium and squamous cell
      carcinoma (p < 0.001). All squamous cell carcinomas exhibited TLR9 expression
      that was positively associated with a high grade (p < 0.05), the presence of
      lymph node metastases (p < 0.05) and previously undetected distant metastases (p
      < 0.05). CONCLUSIONS: Expression of TLR9 in the basal parts of normal esophageal
      epithelium suggests a role related to cell proliferation and differentation. TLR9
      upregulation detected in dysplastic epithelium and in disseminated carcinomas
      indicates that this protein may serve as a novel marker for esophageal squamous
      dysplasia and carcinoma with metastatic potential.

PMID- 21876326
TI  - German cockroach proteases and protease-activated receptor-2 regulate chemokine
      production and dendritic cell recruitment.
AB  - We recently showed that serine proteases in German cockroach (GC) feces (frass)
      decreased experimental asthma through the activation of protease-activated
      receptor (PAR)-2. Since dendritic cells (DCs) play an important role in the
      initiation of asthma, we queried the role of GC frass proteases in modulating
      CCL20 (chemokine C-C motif ligand 20) and granulocyte macrophage colony
      stimulating factor (GM-CSF) production, factors that regulate pulmonary DCs. A
      single exposure to GC frass resulted in a rapid, but transient, increase in GM
      CSF and a steady increase in CCL20 in the airways of mice. Instillation of
      protease-depleted GC frass or instillation of GC frass in PAR-2-deficient mice
      significantly decreased chemokine release. A specific PAR-2-activating peptide
      was also sufficient to induce CCL20 production. To directly assess the role of
      the GC frass protease in chemokine release, we enriched the protease from GC
      frass and confirmed that the protease was sufficient to induce both GM-CSF and
      CCL20 production in vivo. Primary airway epithelial cells produced both GM-CSF
      and CCL20 in a protease- and PAR-2-dependent manner. Finally, we show a decreased
      percentage of myeloid DCs in the lung following allergen exposure in PAR-2
      deficient mice compared to wild-type mice. However, there was no difference in GC
      frass uptake. Our data indicate that, through the activation of PAR-2, allergen
      derived proteases are sufficient to induce CCL20 and GM-CSF production in the
      airways. This leads to increased recruitment and/or differentiation of myeloid DC
      populations in the lungs and likely plays an important role in the initiation of
      allergic airway responses.

PMID- 21876327
TI  - Impact of metabolic syndrome on biochemical recurrence of prostate cancer after
      radical prostatectomy.
AB  - INTRODUCTION: Metabolic syndrome (MS) is linked to hormone-dependent cancers. Its
      prognostic implication in prostate cancer (PCa) is unclear. We analyzed the
      impact of MS in the survival of men with PCa treated surgically. PATIENTS AND
      METHODS: We studied patients with PCa, treated surgically between 1990 and 2007,
      and compared the survival of men with MS (group 1) and without MS (group 2). A
      subgroup analysis of those in stage pT2 was also performed. We calculated
      biochemical progression-free survival (bPFS) and cancer-specific survival, and
      the relation of clinical and pathological variables with these end-points.
      RESULTS: 65 men had MS. The 5- and 10-year bPFS in group 1 was 36 and 32% vs. 72
      and 68% in group 2 (p < 0.0001). In multivariate analysis, prostate-specific
      antigen (p = 0.001) and MS (p < 0.0001) predicted biochemical
      progression/recurrence (BP/R). There was no difference in cancer-specific
      survival between groups (p = 0.40). Of 146 men in stage pT2, 38 had MS; group 1
      men had worse 5- and 10-year bPFS (55 and 48%) than group 2 (80 and 73%; p =
      0.001). In multivariate analysis, MS was the strongest predictor of BP/R (p =
      0.0007). CONCLUSIONS: MS is related to adverse characteristics in PCa and confers
      poor bPFS after radical prostatectomy. MS is independently associated to the risk
      of BP/R.

PMID- 21876328
TI  - Comment on Ekinci et al.: A randomized comparison of droperidol, metoclopramide,
      tropisetron, and ondansetron for the prevention of postoperative nausea and
      vomiting.

PMID- 21876330
TI  - Serous adenocarcinoma of the uterine cervix: a clinicopathological study of 12
      cases and a review of the literature.
AB  - BACKGROUND/AIMS: To determine the clinicopathological characteristics and
      potentially associated outcomes in patients diagnosed with serous adenocarcinoma
      of the uterine cervix. METHODS: The records of surgically-treated patients with
      pathological stage pT1b-2b serous adenocarcinoma were reviewed. RESULTS: Of 12
      patients with serous adenocarcinoma who underwent radical hysterectomy, five had
      pT1b1N0 disease, two pT1b1N1, two pT1b2N0, and three pT2bN1. The 5-year overall
      survival rate for patients with or without parametrial involvement (pT2b vs.
      pT1b) was 0 and 89%, respectively. The 3-year recurrence-free survival rate for
      those with or without parametrial involvement was 33 and 89%, respectively. Four
      patients suffered recurrence, namely one of those who had pT1b (1/9, 11%) and 3
      of those who had pT2b disease (100%). The sites of recurrence of pT2b disease
      were outside the pelvis in all 3 patients. Of these, 2 (67%) had peritoneal
      spread and 1 distant node metastasis. CONCLUSION: While patients with
      pathological stage pT1b disease may have a relatively favorable outcome after
      radical surgery, those with more advanced disease have a poor prognosis because
      of extra-pelvic recurrence.

PMID- 21876331
TI  - Renal angiomyolipoma during pregnancy: review of the literature.
AB  - The incidence of renal angiomyolipoma (RA) is 0.3% in the general population, and
      even more infrequent during pregnancy. Pregnancy can increase the risk of
      rupture, although the causal mechanism is still not clearly defined. We completed
      a Medline literature search for articles on RA and pregnancy and its
      complications. We identified 16 articles (all case reports), but selected only 13
      because of unavailable data in the 3 other articles. We report the case of a 30
      year-old primiparous woman who presented at the emergency ward with a non
      reassuring pattern at fetal monitoring; an urgent cesarean section was decided
      and carried out. After surgery, a wide retroperitoneal hematoma was observed
      caused by the rupture of an RA. Conservative management by means of arterial
      embolism was done and the patient was discharged on postoperative day 10. RAs
      seem to have a higher risk of rupture during pregnancy, but they should be
      managed conservatively when hemodynamically possible. Individualization of each
      case is necessary in order to achieve the best outcome for both the mother and
      fetus.

PMID- 21876332
TI  - Aggregates of cAMP-dependent kinase isoforms characterize different areas in the
      developing central nervous system of the chicken, Gallus gallus.
AB  - The intracellular second messenger adenosine 3',5'-cyclic monophosphate (cAMP)
      acts mainly through cAMP-dependent protein kinases (PKA). In mammals and
      reptiles, the PKA regulatory isoforms (RI and RII) are differentially distributed
      among the various brain areas and cell types, according to the age of the animal.
      Since PKA distribution may be an additional marker for homologous areas, PKA
      regulatory subunit types RI and RII were examined in the chicken brain, a species
      not yet investigated. Chicken brains were examined from prehatching to adult age,
      by means of immunohistochemistry and biochemical characterization. Most PKA
      regulatory subunits were segregated in discrete non-soluble clusters that
      contained either RI or RII. While RII aggregates were present also in non
      neuronal cells, RI aggregates were detected only in neurons of some brain areas
      that are mainly related to the telencephalon. They appeared later than RII
      aggregates; their presence and location varied during development. RI aggregates
      were detected first in the olfactory bulb, around embryonic day 14; within 3 days
      they appeared in the hyperpallium and nidopallium, where the most intense
      labeling was observed in the perihatching period. Fainter RI aggregates persisted
      up to 3 years in the olfactory bulb and nidopallium caudale. Less intense RI
      aggregates were present for a shorter time, from 2 weeks to 3 months, in the
      septal nuclei, thalamic medial nuclei, periventricular hypothalamus, optic tectum
      periventricular area, brainstem reticular formation and spinal cord substantia
      gelatinosa. RI aggregates were not detected in many brain areas including the
      arcopallium, striatum and cranial nerve nuclei. RII distribution showed less
      variation during development. From embryonic day 12, some insoluble RII
      aggregates were detected in the brain; however, only minor modifications were
      observed in positive structures once they started to harbor insoluble RII
      aggregates. The present results suggest that the distribution of PKA aggregates
      may assist in characterizing phylogenetically homologous structures of the
      vertebrate central nervous system and may also unravel biochemical differences
      among areas considered homologous.

PMID- 21876333
TI  - Prenatal and postnatal imaging of multiple intracranial lipomas: report of a
      case.
AB  - OBJECTIVES: To report the antenatal pictures of a fetus with multiple
      intracranial lipomas. METHODS: A 36-year-old primigravida, 33 weeks of gestation,
      was referred to our ultrasound laboratory due to sonographic suspicion of an
      intracranial hemorrhage. RESULTS: At 2D and 3D ultrasound imaging, three
      separated round-shaped hyperechoic intracranial masses compatible with multiple
      lipomas were documented. Absence of corpus callosum was associated. Sonographic
      findings were confirmed by antenatal and postnatal MRI. CONCLUSIONS: Multiple
      intracranial lipomas in a fetus with absent corpus callosum have been
      infrequently described. Prognostic implications remain uncertain.

PMID- 21876334
TI  - A new hypothesis about neuronal degeneration appeared after a rat model of
      menopause.
AB  - OBJECTIVE: Estrogen is suggested to be one of the most important regulators of
      neuronal function, including neuronal proliferation, survival and plasticity.
      There is a broad consensus that the loss of ovarian hormones is associated with
      neurodegeneration in the hippocampus that leads to cognitive impairment. METHODS:
      A total of 8 female rats which were subjected to bilateral ovariectomy were
      included in this study. After ovariectomy, the rats were housed for 123 days in a
      standard laboratory. At the end of the 123 days, the rats were euthanized and the
      brain sections were investigated by conventional light microscopic and electron
      microscopic techniques. RESULTS: The regular structure of almost all axon
      extensions was lost. The majority of these extensions had a sawtooth-like
      appearance in longitudinal section profiles. Especially in transfer section
      profiles of myelinated axons, some morphological changes were shown which may be
      matched up with light microscopic findings. CONCLUSIONS: Deficiency of estrogen
      will initially affect microtubule organization. When this organization breaks
      down, it will physically cause the distribution of the normal structure of axonal
      plasmalemma. This in turn will lead to the distribution of physical organizations
      of estrogen and other different types of receptors which are placed in both the
      membrane and microtubules in the axon.

PMID- 21876335
TI  - Changes of stage, predictive factors and adjuvant treatment modalities in
      seminomatous testicular cancer from 1987 to 2007 and their impact on the status
      of metastasis, recurrence-free and overall survival: a single-center analysis.
AB  - INTRODUCTION: To observe the changing presentation of seminomatous testicular
      cancer (STC), placing particular emphasis on predictive factors with a view to
      evaluating their impact on the status of metastasis, recurrence-free survival
      (RFS) and overall survival (OAS). MATERIALS AND METHODS: 180 patients with STC
      were evaluated retrospectively. Four study periods were generated and compared
      for changes. The data were analyzed for predictive factors for metastasis. Mean
      follow-up was 83 months (range 10-246, patients alive = 146). RESULTS: The number
      of STC patients increased constantly throughout 2007. From 1992 onwards,
      significantly more patients were diagnosed as being in CS1 (p = 0.001). The odds
      ratio (OR) of metastasis was significantly higher for pT3 than pT2 STC (OR 12.4
      vs. 1.7; p = 0.003); pT1 tumors showed a lower risk factor. The 10- and 15-year
      RFS were 91 and 85%, respectively. Patients in clinical stages higher than CS1
      (CS>1) had significantly reduced RFS (p < 0.001). The 5- and 10-year OAS were 97
      and 96%, respectively. Patients in CS>1 had significantly reduced OAS rates (p =
      0.013). CONCLUSIONS: The number of STC cases is increasing, particularly in the
      case of patients in CS1. This emphasizes the need for surveillance regimens and
      makes the evaluation of predictive factors for metastasis, recurrence and
      survival essential.

PMID- 21876336
TI  - The Dowager's hump: an early start?
AB  - BACKGROUND: A recent study has shown that biomarkers relating to the variation of
      muscle strength with age exhibited gender differences. OBJECTIVE: To discover
      whether gender differences in kyphosis and its progression with age might be
      explained in a related manner. METHODS: Relevant aspects of muscular ageing, and
      related changes in the Cobb angle (a measure of kyphosis) were examined and
      linked to data on the gerontology of musculature. A hypothesis regarding
      embryonic antecedents was advanced. RESULTS: Kyphosis appears to rest on a
      multifactorial basis, with age and muscular changes playing potentially important
      roles. CONCLUSIONS: The role of muscle strength as a cause of kyphosis merits
      further investigation. Both muscular and kyphotic studies should be repeated on
      the same subjects, and relevant embryonic antecedents be examined. A study of the
      relation between gonadal and antenatal muscular development might yield
      conclusive results.

PMID- 21876337
TI  - The hippocampus of food-storing birds.

PMID- 21876338
TI  - Cutaneous granulomas in ataxia telangiectasia and other primary
      immunodeficiencies: reflection of inappropriate immune regulation?
AB  - BACKGROUND: Non-infective cutaneous granulomas with unknown pathogenesis occur in
      various primary immunodeficiencies (PIDs) including ataxia telangiectasia (A-T).
      OBJECTIVE: To find a common immunological denominator in these cutaneous
      granulomas. METHODS: The dermatological and immunological features of 4 patients
      with A-T and cutaneous granulomas were described. The literature on skin
      granulomas in A-T and in other PIDs is reviewed. RESULTS: All 4 A-T patients had
      progressive granulomas on their limbs and showed decreased IgG and IgA
      concentrations with normal IgM levels. They had a marked decrease in B cells and
      naive T cells coinciding with the appearance of the cutaneous granulomas. Similar
      B- and T-cell abnormalities were described in patients with other PIDs with skin
      granulomas. CONCLUSIONS: We hypothesize that the pathogenesis of these skin
      granulomas is related to immune dysregulation of macrophages due to the absence
      of naive T cells with an appropriate T-cell receptor repertoire and the unopposed
      activity of gammadelta T cells and/or natural killer cells.

PMID- 21876339
TI  - A missense mutation in the death domain of EDAR abolishes the interaction with
      EDARADD and underlies hypohidrotic ectodermal dysplasia.
AB  - BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a rare condition
      characterized by hypotrichosis, hypohidrosis and hypodontia. The disease shows X
      linked recessive, autosomal-dominant or autosomal-recessive inheritance trait. X
      linked form of HED is caused by mutations in the EDA gene, while autosomal forms
      are caused by mutations in either EDAR or EDARADD genes. METHODS: We analyzed the
      DNA from a Japanese patient with HED through direct sequencing, and also
      performed functional studies for the mutation. RESULTS: We identified a
      homozygous missense mutation c.1073G>A (p.R358Q) in the EDAR gene of the patient,
      which was a nonconservative amino acid substitution within the death domain of
      EDAR protein. We demonstrated that the p.R358Q mutant EDAR protein lost its
      affinity to EDARADD, leading to reduced activation of the downstream NF-kappaB.
      CONCLUSION: Our data further suggest the crucial role of the EDAR signaling in
      development of hair, teeth, and sweat gland in humans.

PMID- 21876340
TI  - Efficacy of paroxetine in primary palmoplantar hyperhidrosis occurring with
      juvenile myoclonic epilepsy.
AB  - Primary palmoplantar hyperhidrosis (PPH) is believed to be a dysfunction of
      emotional sweating, with an estimated prevalence of around 3%. Several treatment
      options including topical antiperspirants, tap water iontophoresis, botulinum
      toxin injections, oral anticholinergics, and tricyclic antidepressants are
      available, each with a significant adverse event profile. For the first time, we
      report a PPH patient with comorbid juvenile myoclonic epilepsy (JME) treated
      successfully with a combination of paroxetine and divalproex sodium. Paroxetine
      resulted in improvement in PPH, possibly through its anticholinergic and/or
      noradrenergic actions. Though the occurrence of PPH and JME together seems to be
      a chance association, some common frontal lobe mechanisms may be involved that
      need to be explored further.

PMID- 21876341
TI  - Characterization of patient-reported outcomes in moderate to severe psoriasis.
AB  - BACKGROUND: The Patient Benefit Index (PBI) is a recently developed instrument to
      assess patient satisfaction with treatment. It has been applied to only a limited
      number of psoriasis patients. OBJECTIVE: Characterization of patient-reported
      outcomes (PRO) in patients with moderate to severe psoriasis. METHODS: 1787
      patients with plaque psoriasis were documented. Psoriasis Area and Severity Index
      (PASI), body surface area (BSA), Dermatology Life Quality Index (DLQI) and PBI
      were determined. Correlations were calculated and the persistence of PBI
      improvement and strength of treatment effect were evaluated. A regression
      analysis was performed to characterize predictors of PBI and DLQI improvements.
      RESULTS: Significant correlations exist between DeltaPASI/DeltaBSA and DeltaDLQI.
      Also, DLQI and PBI are correlated. Improvement in the skin condition has a
      positive and sustainable impact on all need dimensions of the PBI. The best early
      predictor for PBI was PASI 75 at treatment week 8, relevant factors predicting
      quality of life were PBI/subscale 4, (reducing physical impairment), DeltaBSA and
      DeltaPASI. CONCLUSION: Improvement in skin condition correlates with improvements
      in quality of life in patients with plaque psoriasis. Successful treatment leads
      to significant and sustainable patient benefit. While PBI subscale 4 is a good
      predictor for quality of life, more work is necessary to identify potential
      predictors for patient benefit.

PMID- 21876342
TI  - Pressure bandage as an effective treatment for intralymphatic histiocytosis
      associated with rheumatoid arthritis.
AB  - The patient is a 71-year-old male who has been suffering from rheumatoid
      arthritis for over 20 years. He first noticed the erythema on his right forearm
      in 2008, which got worse in 2009. Topical corticosteroids were not effective, and
      a skin biopsy was performed. Histopathologic examination showed aggregation of
      the inflammatory cells in the dermal vessels. Those cells were positive for CD68
      and CD31 and all the surrounding vessels expressed D2-40 and CD31. We diagnosed
      him with intralymphatic histiocytosis. One week after the skin was biopsied, only
      the part of the erythematous lesion covered by skin tape had improved, suggesting
      that pressure on the lesion might improve the erythematous eruption. We therefore
      used a pressure bandage elbow supporter in addition to topical treatment. The
      lesion improved 3 months later and was totally diminished after 9 months.
      Combined with previously reported cases, our case suggested that intralymphatic
      histiocytosis is closely related to lymphostasis.

PMID- 21876343
TI  - The pseudoautosomal region and sex chromosome aneuploidies in domestic species.
AB  - The pseudoautosomal region (PAR) is a unique and specialized segment on the
      mammalian sex chromosomes with known functions in male meiosis and fertility.
      Detailed molecular studies of the region in human and mouse show dramatic
      differences between the 2 PARs. Recent mapping efforts in horse, dog/cat,
      cattle/ruminants, pig and alpaca indicate that the PAR also varies in size and
      gene content between other species. Given that PAR genes escape X inactivation,
      these differences might critically affect the genetic consequences, such as
      embryonic survival and postnatal phenotypes of sex chromosome aneuploidies. The
      aim of this review is to combine the available information about the organization
      of the PAR in domestic species with the cytogenetic data on sex chromosome
      aneuploidies. We show that viable XO individuals are relatively frequently found
      in species with small PARs, such as horses, humans and mice but are rare or
      absent in species in which the PAR is substantially larger, like in
      cattle/ruminants, dogs, pigs, and alpacas. No similar correlation can be detected
      between the PAR size and the X chromosome trisomy in different species. Recent
      evidence about the likely involvement of PAR genes in placenta formation, early
      embryonic development and genomic imprinting are presented.

PMID- 21876344
TI  - mRNA expression of bone morphogenetic proteins and their receptors in human renal
      cell carcinoma.
AB  - INTRODUCTION: Bone morphogenetic proteins (BMPs) have been studied in several
      cancers, but only limited information is available about renal cell carcinomas
      (RCCs). We determined the expression of mRNA of several BMP ligands and BMP
      receptors (BMPRs) in healthy kidney tissue and RCCs, and data were compared to
      clinicopathological parameters. MATERIAL AND METHODS: Sixty-four samples of RCCs
      and healthy renal tissues were prospectively examined. The expression of BMP2,
      BMP4, BMP6, BMP7, BMPRIA, BMPRIB and BMPRII mRNA was determined using
      semiquantitative reverse transcriptase-polymerase chain reaction. RESULTS: The
      expression levels of different BMP ligands and BMPRs were considerably higher in
      RCCs than in normal kidney tissue. BMP ligands showed elevated expression in
      clear-cell RCCs, whereas all three BMPRs showed higher expression levels in non
      clear-cell RCCs. In clear-cell RCCs, the expression levels of BMP2 progressively
      increased and expression levels of BMP6, BMP7 and BMPRIB were lost with higher
      tumor stage. CONCLUSIONS: All BMPs and their receptors have stronger expression
      levels in RCC. The expression level of BMP2 is strongly elevated in kidney
      cancer.

PMID- 21876345
TI  - Clinical and molecular characterization of a combined 17p13.3 microdeletion with
      partial monosomy 21q21.3 in a 26-year-old man.
AB  - We led a clinical and molecular characterization of a patient with mild mental
      delay and dysmorphic features initially referred for cytogenetic exploration of
      an azoospermia. We employed FISH and array CGH techniques for a better definition
      and refinement of a double chromosome aberration associating a 17p microdeletion
      with partial monosomy 21q due to 1:3 meiotic segregation of a maternal reciprocal
      translocation t(17;21)(p13.3;q21.2) revealed after banding analysis. Brain MRI
      depicted partial callosal and mild diffuse cerebral atrophies, but without
      expected signs of lissencephaly. The patient's karyotype formula was:
      45,XY,der(17)t(17;21)(p13.3;q21.2)mat,-21. FISH study confirmed these
      rearrangements and array CGH analysis estimated the loss sizes to at least 635 kb
      on chromosome 17 and to 15.6 Mb on chromosome 21. The absence of lissencephaly
      and major brain malformations often associated with 17p terminal deletions could
      be attributed to the retention of PAFAH1B1, YWHAE and CRK genes. Dysmorphic
      features, moderate mental impairment and minor brain malformations could result
      from the 21q monosomy and particularly the partial deletion of the APP-SOD1
      region. Azoospermia should result from gamete apoptosis induced by a control
      mechanism triggered in response to chromosome imbalances. Our study provides an
      additional case for better understanding and delineating both 17p and 21q
      deletions.

PMID- 21876346
TI  - Evaluation of JNK blockade as an early intervention treatment for type 1 diabetic
      nephropathy in hypertensive rats.
AB  - BACKGROUND/AIMS: The c-Jun amino-terminal kinase (JNK) signaling pathway is
      activated in human kidney diseases and promotes renal injury in experimental
      glomerulonephritis. In this study, we examined whether JNK signaling plays a role
      in the development of diabetic nephropathy or in regulating hypertension, which
      exacerbates diabetic renal injury. METHODS: Diabetes was induced in spontaneously
      hypertensive rats (SHR) using streptozotocin. At week 16 of diabetes, rats with
      equivalent hyperglycemia and albuminuria were randomized into groups which
      received no treatment, vehicle alone or a selective JNK inhibitor (CC-930, 60
      mg/kg/bid) for 10 weeks. These rats were assessed for hypertension and
      progression of renal damage. RESULTS: At week 16, diabetic rats showed increased
      kidney JNK activation compared with nondiabetic controls. Effective JNK
      inhibition was demonstrated at week 26 by reductions in c-Jun phosphorylation. CC
      930 did not affect blood pressure, kidney hypertrophy, glomerular
      hyperfiltration, podocyte loss, glomerular fibrosis or tubulointerstitial injury
      in diabetic SHR. However, CC-930 reduced macrophages and ccl2 mRNA levels in
      diabetic kidneys. In contrast, CC-930 exacerbated albuminuria at week 26, which
      was associated with reduced glomerular mRNA levels of the podocyte-specific
      molecules, nephrin and podocin. CONCLUSION: JNK inhibition does not prevent the
      progression of early diabetic renal injury in hypertensive rats, which contrasts
      with the ability of JNK inhibition to suppress albuminuria and injury in
      experimental glomerulonephritis.

PMID- 21876347
TI  - Advanced glycation urinary protein-bound biomarkers and severity of diabetic
      nephropathy in man.
AB  - BACKGROUND/AIMS: The formation of advanced glycation end products (AGEs) is
      accelerated in patients with diabetic nephropathy. The aim of this study was to
      ascertain if the urinary excretion of proteins modified by advanced glycation can
      be used as biomarkers for albuminuria in individuals with type 1 or type 2
      diabetes. METHODS: Community-based patients with type 1 (n = 68) or type 2
      diabetes (n = 216) attending a diabetes clinic of a tertiary referral hospital
      were classified as having normoalbuminuria (Normo, albumin excretion rate (AER)
      <20 MUg/min), microalbuminuria (Micro, AER 20-200 MUg/min) or macroalbuminuria
      (Macro, AER >=200 MUg/min). Serum and urine AGE-modified proteins were measured.
      RESULTS: In patients with both type 1 diabetes and type 2 diabetes, there was a
      clear association between the degree of albuminuria and urinary AGE-modified
      proteins (p < 0.0001). Exclusive to patients with type 1 diabetes, urinary
      excretion of the AGE carboxymethyllysine correlated with AER, whereas patients
      with type 2 diabetes and macroalbuminuria had an increase in urinary
      methylglyoxal, an AGE intermediate. These changes were independent of isotopic
      glomerular filtration rate levels. Serum concentrations of AGEs or soluble
      receptor for AGEs were not consistently associated with albuminuria in either
      type 1 or type 2 diabetes. CONCLUSIONS: Urinary excretion of proteins modified by
      AGEs may be useful biomarkers of albuminuria in individuals with type 1 and type
      2 diabetes, warranting prospective investigation in larger diabetic cohorts.

PMID- 21876348
TI  - Vascular calcification is associated with cortical bone loss in chronic renal
      failure rats with and without ovariectomy: the calcification paradox.
AB  - BACKGROUND: Increased bone loss has been associated with the development of
      vascular calcification in patients with chronic renal failure (CRF). In this
      study, the effect of impaired bone metabolism on aortic calcifications was
      investigated in uremic rats with or without ovariectomy. METHODS: CRF was induced
      by administration of a 0.75% adenine/2.5% protein diet for 4 weeks. In one group,
      osteoporosis was induced by ovariectomy (CRF-OVX), while the other group
      underwent a sham-operation instead (CRF). A third group consisted of
      ovariectomized rats with normal renal function (OVX). At regular time intervals
      throughout the study, bone status and aortic calcifications were evaluated by in
      vivo micro-CT. At sacrifice after 6 weeks of CRF, bone histomorphometry was
      performed and vascular calcification was assessed by bulk calcium analysis and
      Von Kossa staining. RESULTS: Renal function was significantly impaired in the CRF
      OVX and CRF groups. Trabecular bone loss was seen in all groups. In the CRF-OVX
      and CRF groups, trabecular bone density was restored after adenine withdrawal,
      which coincided with cortical bone loss and the development of medial
      calcifications in the aorta. No significant differences with regard to the degree
      of aortic calcifications were seen between the two CRF groups. Neither cortical
      bone loss nor calcifications were seen in the OVX group. Cortical bone loss
      significantly correlated with the severity of vascular calcification in the CRF
      OVX and CRF groups, but no associations with trabecular bone changes were found.
      CONCLUSIONS: Cortical rather than trabecular bone loss is associated with the
      process of calcification in rats with adenine- induced CRF.

PMID- 21876349
TI  - Antiproteinuric effect of chemokine C-C motif ligand 2 inhibition in subjects
      with acute proliferative lupus nephritis.
AB  - BACKGROUND/AIMS: To test the role of chemokine C-C motif ligand 2 (CCL2) in the
      pathogenesis of lupus nephritis (LN), we evaluated the effects of CCL2 inhibition
      by bindarit therapy in patients with systemic lupus and active renal disease.
      METHODS: In this proof-of-concept, prospective, randomized, double-blind clinical
      study, 22 subjects with acute LN were assigned on a 1:1 ratio to 24-week
      treatment with bindarit (1,200 mg/day) or matching placebo. All subjects were on
      the same standardized steroid background therapy. Urinary CCL2, urinary albumin
      excretion (UAE), estimated glomerular filtration rate, time to remission and time
      to relapse of LN were compared between groups. RESULTS: Urinary CCL2
      significantly decreased during bindarit therapy (p = 0.008 vs. baseline) with a
      reduction that approximated 50% at study end. CCL2 reduction was paralleled by a
      persistent reduction in UAE that averaged 80% vs. baseline and approximated 90%
      at study end. Renal function recovery was similar and no difference was found in
      terms of time to remission and time to relapse of LN between treatment arms.
      Treatment was safe and well tolerated in all patients. CONCLUSION: In lupus
      subjects with active nephritis, bindarit significantly reduced albuminuria and
      urinary CCL2 levels. This study provides the background for longer trials to test
      renoprotective effect of CCL2 inhibition in LN.

PMID- 21876350
TI  - Development and validation of a new dry weight estimation method using single
      frequency bioimpedance in hemodialysis patients.
AB  - BACKGROUND: We proposed a new method to estimate dry weight (DW) using single
      frequency bioimpedance. METHODS: We hypothesized that the change in whole body
      resistance at 50 kHz (R(50)) was proportional to the ultrafiltration volume (UFV)
      during a hemodialysis (HD) session. When the targeted resistance estimated in
      healthy subjects was reached, the patient achieved his/her DW. UFV and R(50) were
      monitored in 40 HD patients. Another 43 HD patients were stratified into 2 groups
      to validate this method. RESULTS: The change in whole body resistance was
      proportional to UFV in each of the 40 HD patients. In the DW(decrease) group, pre
      dialysis systolic blood pressure (n = 29, 154.5 +/- 22.8 vs. 146.9 +/- 22.3, p <
      0.05) and antihypertensive medicine (4.7 +/- 3.6 vs. 3.3 +/- 2.2, p < 0.05)
      decreased without adverse symptoms change. In the DW(increase) group, the number
      of adverse symptoms in 1 week (n = 14, 26 vs. 6, p < 0.05) decreased without a
      change in systolic blood pressure. CONCLUSION: This method may become a
      convenient and cheaper way to estimate DW in HD patients.

PMID- 21876351
TI  - Adsorptive modulation of inflammatory mediators dampens endothelial cell
      activation.
AB  - AIM: In this study, the effect of specific or selective adsorption of
      inflammatory mediators on endothelial activation was assessed. METHODS:
      Conditioned medium was obtained by stimulation of monocytic THP-1 cells with
      lipopolysaccharide and treated either with an adsorbent specific for tumour
      necrosis factor-alpha or with an albumin-coated polystyrene-divinylbenzene
      copolymer which selectively binds a range of cytokines. Thereafter, the
      conditioned medium was applied to endothelial cells in culture. RESULTS:
      Adsorption of inflammatory mediators resulted in significantly decreased
      endothelial cell activation, as shown by reduced interleukin (IL)-6 and IL-8
      secretion from endothelial cells as well as reduced surface expression of the
      adhesion molecules intercellular adhesion molecule-1 and E-selectin. The effect
      was more pronounced the earlier the mediator modulation was performed.
      CONCLUSION: Adsorptive modulation of inflammatory mediators dampens endothelial
      cell activation and may thus be beneficial as supportive therapy in sepsis.

PMID- 21876352
TI  - Increased calcification and protein nitration in arteries of chronic kidney
      disease patients.
AB  - BACKGROUND: Cardiovascular disease in chronic kidney disease (CKD) has peculiar
      characteristics. The aim of this study was to analyze atherosclerosis, vascular
      calcification and nitration in arteries from CKD patients. METHODS: External
      iliac and renal artery segments from 27 stage 5 CKD patients and 25 donor
      controls, respectively, were collected during the transplantation procedure.
      RESULTS: CKD patients presented a significantly higher degree of lesion. In a
      large proportion (72%) of CKD patients, we observed vascular calcifications.
      Immunohistochemistry for nitrotyrosine revealed a significant increase in
      nitrotyrosine production in arteries from CKD patients compared with control
      donors. In addition, within CKD patients, nitrotyrosine staining was
      significantly stronger in arteries with media calcification when compared with
      arteries without media calcification. CONCLUSION: The arteriopathy in the CKD
      patients appears in an early age and seems to be distinct from the arteriopathy
      of the general population, especially due to intense calcification and vascular
      oxidative stress.

PMID- 21876353
TI  - Two-year vascular event rates in patients with symptomatic cerebrovascular
      disease: the REACH registry.
AB  - BACKGROUND AND PURPOSE: Few practice-based studies have reported vascular outcome
      events among patients with cerebrovascular disease (CeVD). We describe 2-year
      vascular outcomes among symptomatic CeVD patients from the REduction of
      Atherothrombosis for Continued Health (REACH) Registry. METHODS: Vascular events
      (stroke; myocardial infarction, MI; cardiovascular death, CV death;
      hospitalization) were studied among symptomatic CeVD patients from a prospective
      cohort of stable outpatients with established atherothrombosis or >=3
      atherothrombotic risk factors. RESULTS: Of the 69,055 patients in REACH, 18,992
      (28%) had symptomatic CeVD, of which outcome data were available for 18,189
      patients. At 2 years, the frequency of non-fatal stroke was 5.93% (95% CI 5.22
      6.64), non-fatal MI 2.21% (95% CI 1.65-2.76), CV death 4.45% (95% CI 3.66-5.22),
      combined vascular endpoint 11.48% (95% CI 10.46-12.49), and all deaths 7.39% (95%
      CI 6.34-8.42). The frequency of stroke, MI, CV death, or hospitalization for
      atherothrombotic events was 21.05% (95% CI 20.05-22.03). Event rates were lowest
      among patients with CeVD alone and highest among patients with CeVD, coronary
      artery disease, and peripheral artery disease. Other predictors of the primary
      outcome were increasing age, history of diabetes, current smoking, asymptomatic
      carotid stenosis, and carotid plaque. Outcomes were similar across geographical
      regions. CONCLUSIONS: Symptomatic CeVD patients encounter high vascular event
      rates despite treatment. Recurrent nonfatal stroke is more common than nonfatal
      MI.

PMID- 21876354
TI  - Comparison of the effects of whole and juiced fruits and vegetables on enamel
      demineralisation in situ.
AB  - We compared the effect on enamel demineralisation in situ of both whole and
      juiced fruits and vegetables. Volunteers wore removable mandibular appliances
      carrying pre-demineralised human enamel slabs and consumed one of the test foods
      7 times a day for 10 days. The test foods were apples, oranges, grapes, carrots,
      and tomatoes, consumed either whole (sugars located intrinsically) or as a juice
      (extrinsic or free sugars). Raisins containing 64% sugars, but intrinsic by
      definition, were also studied. The mineral profile of the enamel slabs was
      studied before and after the test period using transverse microradiography and
      showed further demineralisation for all test foods, irrespective of the form of
      consumption. Significant demineralisation was also observed with raisins. No
      significant differences were found between the solid and juiced foods. In
      conclusion, sugars present intrinsically on consumption had a similar
      demineralising potential as free sugars and could not be considered less
      cariogenic.

PMID- 21876355
TI  - Increased matrix metalloproteinase-2 and bone sialoprotein response to human
      coronal caries.
AB  - BACKGROUND: It has been suggested that host matrix metalloproteinase-2 (MMP-2)
      present in dentin may be involved in caries progression, however, its response to
      caries is not known. Bone sialoprotein (BSP) has been implicated in dentin
      mineralization and MMP-2 modulation. OBJECTIVE: To identify and compare the
      distribution of MMP-2 and BSP in healthy human coronal dentin and those with
      early caries. METHODS: Freshly extracted 3rd molars and premolars with and
      without early caries were fixed, demineralized and subjected to
      immunohistochemistry using a monoclonal anti-MMP-2 antibody and monoclonal anti
      BSP antibody with an avidin-biotin complex method. Immunoreactivity was
      visualized with 3,3'-diaminobenzidine substrate and observed under light
      microscopy. RESULTS: Immunohistochemical analysis revealed that MMP-2 and BSP are
      not detected in the tubule lumens of healthy dentin. However, intense
      immunoreactivity for MMP-2 and BSP was detected in association with the full
      length of the caries-affected dentinal tubules. The MMP-2 and BSP at the dentino
      enamel junction appeared unaltered. CONCLUSION: The results indicate that MMP-2
      and BSP may be actively secreted by odontoblasts in response to carious insult.
      MMP-2 and BSP accumulation in the caries-affected dentinal tubules may indicate
      their potential involvement in the host defense mechanism which results in
      calcification of regions affected by the carious process.

PMID- 21876356
TI  - Decrease of GABAergic markers and arc protein expression in the frontal cortex by
      intraventricular 192 IgG-saporin.
AB  - BACKGROUND/AIMS: Previous studies used 192 IgG-saporin to study cholinergic
      function because of its facility for selective lesioning; however, results varied
      due to differences in the methods of administration and behavioral tests used. We
      examined an animal model of dementia using 192 IgG-saporin to confirm its
      features before applying this model to research of therapeutic drugs or
      electrical stimulation techniques. METHODS: Features were verified by the Morris
      water maze test, immunochemistry, and Western blotting. Animals were examined
      after intraventricular injection of 192 IgG-saporin (0.63 MUg/MUl; 6, 8, and 10
      MUl) or phosphate-buffered saline. RESULTS: In the acquisition phase of the
      Morris water maze test, the latencies of the injection groups were significantly
      delayed, but recovered within 1 week. In the probe test, 2 of 4 indices (time in
      the platform zone and the number of crossings) were significantly different in
      the 8-MUl injection group. Immunohistochemistry revealed the extent of
      cholinergic destruction. Activity-regulated cytoskeleton-associated protein and
      glutamate decarboxylase expression significantly decreased in the frontal cortex
      (8- and 10-MUl groups), but not in the hippocampus. CONCLUSION: Spatial memory
      impairment was associated with cholinergic basal forebrain injury as well as
      frontocortical GABAergic hypofunction and synaptic plasticity deceleration.

PMID- 21876357
TI  - A systematic literature review of cerebrospinal fluid biomarkers in delirium.
AB  - BACKGROUND: Cerebrospinal fluid (CSF) analysis has great potential to advance
      understanding of delirium pathophysiology. METHODS: A systematic literature
      review of CSF studies of DSM or ICD delirium was performed. RESULTS: In 8 studies
      of 235 patients, delirium was associated with: elevated serotonin metabolites,
      interleukin-8, cortisol, lactate and protein, and reduced somatostatin, beta
      endorphin and neuron-specific enolase. Elevated acetylcholinesterase predicted
      poor outcome after delirium and higher dopamine metabolites were associated with
      psychotic features. CONCLUSIONS: No clear conclusions emerged, but the current
      literature suggests multiple areas for further investigation with more detailed
      studies.

PMID- 21876359
TI  - Determinants of infarction patterns in cardioembolic stroke.
AB  - BACKGROUND: Embolic infarctions from the heart are known to cause multiple
      scattered infarct lesions as well as single, large territorial infarctions.
      However, it remains unknown which factors contribute to these different
      infarction patterns in patients with potential cardiac sources of embolism
      (PCSE). METHODS: We examined 388 ischemic stroke patients with a high-risk PCSE
      using diffusion-weighted imaging. Infarction patterns were categorized into a
      single large lesion, a single small lesion, confluent and additional lesions, or
      small scattered lesions. The relationships between infarction patterns and
      clinical and hematologic parameters were investigated. RESULTS: Of the 388
      patients, a single large lesion was detected in 139 (35.8%), a single small
      lesion in 29 (7.5%), confluent and additional lesions in 171 (44.1%), and small
      scattered lesions in 49 (12.7%). Prior use of antiplatelet agents and
      anticoagulant were associated with the pattern of small scattered lesions and a
      single small lesion, respectively. Additionally, higher white blood cell counts
      were associated with confluent and additional lesions. The type of high-risk PCSE
      was not related to a specific infarction pattern. CONCLUSIONS: These results
      suggest that platelet function and inflammatory processes may directly affect the
      thrombus formation in the cardiac chamber.

PMID- 21876358
TI  - Is moderate red wine consumption safe in inactive inflammatory bowel disease?
AB  - BACKGROUND: Alcohol consumption is a potential trigger for inflammatory bowel
      disease (IBD) flare because of alcohol-induced oxidative stress and its
      deleterious effects on gut barrier function. Additionally, we have recently shown
      that alcohol consumption is associated with more symptoms in IBD. However, it is
      not known whether moderate daily alcohol consumption can modify IBD disease
      activity. To test what effects alcohol may have on patients with IBD, we
      evaluated the effect of moderate daily red wine for 1 week on two factors
      associated with recurrent IBD disease activity: intestinal permeability and stool
      calprotectin. METHODS: To assess the effects of moderate daily alcohol
      consumption on intestinal permeability and inflammation, we recruited 21
      patients: 8 with inactive ulcerative colitis (UC), 6 with inactive Crohn's
      disease (CD), and 7 healthy controls. All participants with IBD completed a
      validated questionnaire on disease activity (Crohn's disease activity index or
      ulcerative colitis clinical activity index), to confirm they had inactive
      disease. All subjects then underwent a baseline assessment that included a blood
      draw, urine collection after sugar challenge, and stool collection. Subjects then
      consumed 1-3 glasses of red wine a day for 1 week (approx. 0.4 g EtOH/kg), and
      repeated the three measures. RESULTS: No subjects flared during the study.
      Moderate alcohol consumption did not significantly change either clinical disease
      activity scores or C-reactive protein. In contrast to healthy subjects, daily
      consumption of red wine significantly (1) decreased stool calprotectin in IBD
      subjects from baseline (p = 0.001) and (2) increased intestinal permeability as
      measured by urinary lactulose/mannitol excretion (marker of small bowel
      permeability) in CD (p = 0.028) or urinary sucralose secretion (marker of large
      bowel permeability) in UC (p = 0.012). CONCLUSIONS: One week of moderate
      consumption of red wine in inactive IBD was associated with a significant
      decrease in stool calprotectin and a significant increase in intestinal
      permeability. Our data suggests that patients with inactive IBD who drink red
      wine daily may be at an increased long-term risk for disease relapse.

PMID- 21876360
TI  - Effects of a supplementation of n-3 polyunsaturated fatty acids with or without
      fish gelatin on gene expression in peripheral blood mononuclear cells in obese,
      insulin-resistant subjects.
AB  - AIM: To investigate gene expression changes in peripheral blood mononuclear cells
      (PBMCs) following an n-3 polyunsaturated fatty acid (PUFA) and n-3 PUFA plus fish
      gelatin (+FG) supplementation. METHODS: A transcriptome comparison of 8-week
      supplementation with n-3 PUFA and n-3 PUFA+FG was carried out in PBMCs of 16
      obese insulin-resistant subjects. RESULTS: Erythrocyte n-3 PUFA concentration
      increased and plasma triglycerides decreased significantly without altering
      inflammatory parameters after both supplementations. n-3 PUFA supplementation
      changed the expression of 805 genes, whereas n-3 PUFA+FG supplementation altered
      the expression of 184 genes. Three genes were commonly changed: fatty acid
      desaturase 1, free fatty acid receptor 3, and ectodysplasin. Pathway analyses
      indicate changes in gene expression via the nuclear receptor peroxisome
      proliferator-activated receptor alpha pathway after both supplementations.
      Further, the extent of modifications in the expression of genes implicated in the
      inflammatory pathways - the oxidative stress response mediated by nuclear factor
      (erythroid-derived 2)-like 2, nuclear transcription factor kappaB, oxidative
      stress, and hypoxia-inducible factor signaling - was different after each
      supplementation. CONCLUSION: Although n-3 PUFA and n-3 PUFA+FG supplementations
      have a distinct impact on gene expression levels, the consequences on biochemical
      parameters and metabolic pathways were comparable after both supplementations.

PMID- 21876361
TI  - Gene polymorphisms and low dietary intake of micronutrients in coronary artery
      disease.
AB  - BACKGROUND/AIMS: Coronary artery disease (CAD) is a complex disorder involving
      genetic and non-genetic factors. Food is an important component of the latter. We
      examined if DNA polymorphisms in genes encoding enzymes of one-carbon metabolism
      coupled with low consumption of micronutrients such as folate, vitamins B(6) and
      B(12) might increase the risk of CAD. METHODS: A case-control study consisting of
      252 CAD patients and 252 controls were included. Three single nucleotide
      polymorphisms (SNP), 2 insertion/deletion and 1 repeat polymorphism were typed.
      The micronutrient intake was estimated from a standard 24-hour dietary recall
      coupled to a food frequency questionnaire. RESULTS: The results suggest an
      association of 'early-onset CAD' with betaine homocysteine S-methyl transferase
      (BHMT) 742G->A SNP (odds ratio = 1.52; 95% confidence interval, 0.96-2.41; p =
      0.04). No association was observed for all age of onset, but more patients than
      controls whose micronutrient intake was in the lowest quintile also carried the
      minor allele (50% patients vs. 37% controls; p = 0.042). Furthermore, dietary
      intake of folate micronutrients below the recommended daily allowance was
      observed in a larger percent of patients than controls with the minor BHMT allele
      (51% patients vs. 44% controls; p = 0.021). CONCLUSIONS: In the presence of the
      minor BHMT allele, a decreased consumption of folate micronutrients might
      increase the risk of CAD.

PMID- 21876362
TI  - Renal anemia treatment with ESA in hemodialysis patients in relation to early
      versus late referral in everyday clinical practice in Central and Eastern
      European countries: baseline data.
AB  - The aim of the study was to collect retrospective data on renal anemia
      management, comorbidities and prospective data on 12-month standard care
      erythropoiesis-stimulating agent (ESA) therapy used in 398 hemodialyzed patients
      in selected Central and Eastern European countries (50 centers in 3 countries).
      Patients were divided into three groups according to ESA therapy start: group A
      ESA (after start of hemodialysis, HD), B-ESA (within 3 months from start of HD),
      C-ESA (more than 3 months before HD). At the chronic kidney disease diagnosis,
      hemoglobin in all patients was 10.3 +/- 2.3 g/dl; however, ferritin, iron, TSAT
      were within reference limits. Early ESA therapy (C) was administered to 10% of
      patients only. 47% of patients received ESA after start of dialysis. Before
      study, the mean weekly ESA dose in group C was statistically lower than in groups
      B and A (p < 0.001). At baseline visit, hemoglobin in group A patients was
      slightly lower than in group B and C patients (p = 0.025). In conclusion, in
      Central and Eastern European countries renal anemia therapy with ESA starts
      shortly before or after start of HD. This highlights important differences in
      standard care in Eastern Europe. However, paradoxically, due to the tight
      reimbursement policy we foresee the clinical implications of the TREAT trial for
      the chronic kidney disease population.

PMID- 21876363
TI  - Dynamic enhancement of the rat inner ear after ultra-small-volume administration
      of Gd-DOTA to the medial wall of the middle ear cavity.
AB  - OBJECTIVE: To investigate minimally invasive administration of contrast agent to
      the middle ear and the enhancement efficacy on the inner ear compartments.
      MATERIALS AND METHODS: An ultra-small volume of gadolinium-tetraazacyclododecane
      tetraacetic acid (Gd-DOTA) was injected onto the medial wall of the rat middle
      ear with a high-performance polyimide tube. The dynamic Gd-DOTA distribution in
      the inner ear was visualized in vivo by MRI. RESULTS: After injection of 2.5 MUl
      of 0.5MGd-DOTA, uptake first occurred in the vestibulum, then in the scala
      vestibuli, and finally in the scala tympani (ST). A significant difference in
      signal intensities among these compartments was demonstrated with an intensity
      gradient, indicating that the vestibulum was the highest and the ST was the
      lowest. After 24 h, Gd-DOTA remained in the inner ear and the vestibule remained
      higher compared to the cochlea. The signal/noise ratio was significantly improved
      by a fluid-attenuated inversion recovery sequence. CONCLUSIONS: This novel
      minimally invasive technique can be applied to both animal studies and clinical
      evaluations of inner ear barrier function and fluid spaces with gadolinium
      enhanced MRI. This technique might also be exploited for use as a minimally
      invasive drug delivery means for inner ear treatment.

PMID- 21876364
TI  - Endoscopic transoral approach for extracranial hypoglossal schwannoma.
AB  - OBJECTIVE: Hypoglossal nerve schwannoma, especially when inside the extracranial
      region, is extremely rare. This report describes a new endoscopic transoral
      approach for the removal of extracranial hypoglossal schwannoma. PATIENTS AND
      METHODS: Three patients (1 male and 2 females, aged 58-63 years) with
      extracranial hypoglossal schwannoma in the paroccipital condyle and the jugular
      foramen were treated solely by an endoscopic transoral approach. All patients
      presented signs of hypoglossal nerve paresis with hemiatrophy of the tongue. In
      addition, one of them had glossopharyngeal nerve paresis, and vagus nerve paresis
      was found in another patient. RESULTS: In all patients, tumors underwent
      successful radical intracapsular removal by the endoscopic transoral approach, as
      confirmed by the postoperative examinations and MRI. No complications occurred
      during or after surgery, except that 1 patient had swallowing difficulties and a
      temporary right vagus palsy during the first day after surgery. All patients were
      followed up for 6 months, and the lack of any recurrence has been confirmed.
      Muscle bulk, motor and swallowing functions, and the vagus palsy improved in all
      patients. CONCLUSION: The endoscopic transoral approach is a safe and useful
      surgical technique for the removal of intracapsular tumors, including
      extracranial hypoglossal schwannomas, which involves minimal invasion.

PMID- 21876365
TI  - Does external pancreatic duct stent decrease pancreatic fistula rate after
      pancreatic resection?: a meta-analysis.
AB  - OBJECTIVES: The use of an external pancreatic duct stent to prevent fistula
      formation of pancreatic anastomosis remains a matter of debate. This study is a
      meta-analysis of the available evidence. METHODS: Articles published until the
      end of March 2011 comparing external stenting and non-stenting in pancreatic
      anastomosis were included. Pooled odds ratios (ORs) and weighted mean differences
      (WMDs) with 95% confidence intervals (95% CI) were calculated using either the
      fixed effects model or random effects model. RESULTS: Six articles were
      identified for inclusion: 3 randomized controlled trials and 3 observational
      clinical studies. The meta-analysis revealed that the use of an external
      pancreatic duct stent was associated with a statistically significant reduction
      in overall postoperative morbidity (OR 0.56; 95% CI 0.39-0.81; p = 0.002),
      pancreatic fistula (OR 0.34; 95% CI 0.23-0.15; p < 0.001), severity of pancreatic
      fistula (OR 0.70; 95% CI 0.32-1.57; p = 0.04), delayed gastric emptying (OR 0.44;
      95% CI 0.25-0.80; p = 0.007), and length of hospital stay (WMD -3.95; 95% CI 
      6.38 to -1.52; p = 0.001). CONCLUSIONS: The current literature suggests that the
      use of an external pancreatic duct stent reduced the leakage rate of pancreatic
      anastomosis after pancreatic resection. and IAP.

PMID- 21876366
TI  - Genetic diversity of cultivable plant growth-promoting rhizobacteria in Korea.
AB  - To elucidate the biodiversity of plant growth-promoting rhizobacteria (PGPR) in
      Korea, 7,638 bacteria isolated from the rhizosphere of plant species growing in
      many different regions were screened. A large number of PGPR were identified by
      testing the ability of each isolate to promote the growth of cucumber seedlings.
      After redundant rhizobacteria were removed via amplified rDNA restriction
      analysis, 90 strains were finally selected as PGPR. On the basis of 16S ribosomal
      RNA sequences, 68 Gram-positive (76%) and 22 Gram-negative (24%) isolates were
      assigned to 21 genera and 47 species. Of these genera, Bacillus (32 species) made
      up the largest complement, followed by Paenibacillus (19) and Pseudomonas (11).
      Phylogenetic analysis showed that most of the Grampositive PGPR fell into two
      categories: low- and high- G+C (Actinobacteria) strains. The Gram-negative PGPR
      were distributed in three categories: alpha-proteobacteria, beta- proteobacteria,
      and gamma-proteobacteria. To our knowledge, this is the largest screening study
      designed to isolate diverse PGPR. The enlarged understanding of PGPR genetic
      diversity provided herein will expand the knowledge base regarding beneficial
      plant-microbe interactions. The outcome of this research may have a practical
      effect on crop production methodologies.

PMID- 21876367
TI  - Effect of fermented sea tangle on the alcohol dehydrogenase and acetaldehyde
      dehydrogenase in Saccharomyces cerevisiae.
AB  - Sea tangle, a kind of brown seaweed, was fermented with Lactobacillus brevis BJ
      20. The gamma-aminobutyric acid (GABA) content in fermented sea tangle (FST) was
      5.56% (w/w) and GABA in total free amino acid of FST was 49.5%. The effect of FST
      on the enzyme activities and mRNA protein expression of alcohol dehydrogenase
      (ADH) and acetaldehyde dehydrogenase (ALDH) involved in alcohol metabolism in
      Saccharomyces cerevisiae was investigated. Yeast was cultured in YPD medium
      supplemented with different concentrations of FST powder [0, 0.4, 0.8, and 1.0%
      (w/v)] for 18 h. FST had no cytotoxic effect on the yeast growth. The highest
      activities and protein expressions of ADH and ALDH from the cell-free extracts of
      S. cerevisiae were evident with the 0.4% and 0.8% (w/v) FST-supplemented
      concentrations, respectively. The highest concentrations of GABA as well as
      minerals (Zn, Ca, and Mg) were found in the cell-free extracts of S. cerevisiae
      cultured in medium supplemented with 0.4% (w/v) FST. The levels of GABA, Zn, Ca,
      and Mg in S. cerevisiae were strongly correlated with the enzyme activities of
      ADH and ALDH in yeast. These results indicate that FST can enhance the enzyme
      activities and protein expression of ADH and ALDH in S. cerevisiae.

PMID- 21876368
TI  - Characterization of novel plasmid p1B146 from Corynebacterium tuberculostearicum.
AB  - Corynebacterium tuberculostearicum B146, a strain derived from healthy human
      skin, contains a medium copy plasmid, p1B146. This plasmid was cloned and its
      complete nucleotide sequence determined. As a result, p1B146 was found to be 4.2
      kb in size with a 53% G+C content, plus six open reading frames (ORFs) were
      distinguished. According to a computer-assisted alignment, two of the ORFs
      exhibited significant similarities to already-known common plasmid proteins, the
      first being the RepA gene, responsible for plasmid replication via a rolling
      circle mechanism, and the second being an FtsK-like protein, the function of
      which remains unclear. The presence and quantity of RNA fragments in the putative
      ORFs were also evaluated.

PMID- 21876369
TI  - Enhancement of gene delivery using novel homodimeric tat peptide formed by
      disulfide bond.
AB  - Cationic liposomes have been actively used as gene delivery vehicle because of
      their minimal toxicity, but their relatively low efficiency of gene delivery is
      the major disadvantage of these vectors. Recently, cysteine residue incorporation
      to HIV-1 Tat peptide increased liposomemediated transfection compared with
      unmodified Tat peptide. Therefore, we designed a novel modified Tat peptide
      having a homodimeric (Tat-CTHD, Tat-NTHD) and closed structure (cyclic Tat)
      simply by using the disulfide bond between cysteines to develop a more efficient
      and safe nonviral gene delivery system. The mixing of Tat-CTHD and Tat-NTHD with
      DNA before mixing with lipofectamine increased the transfection efficiency
      compared with unmodified Tat peptide and lipofectamine only in MCF-7 breast
      cancer cells and rat vascular smooth muscle cells. However, cyclic Tat did not
      show any improvement in the transfection efficiency. In the gel retardation
      assay, Tat-CTHD and Tat-NTHD showed more strong binding with DNA than unmodified
      Tat and cyclic Tat peptide. This enhancement was only shown when Tat-CTHD and Tat
      NTHD were mixed with DNA before mixing with lipofectamine. The effects of Tat-
      CTHD and Tat-NTHD were also valid in the experiment using DOTAP and DMRIE instead
      of lipofectamine. We could not find any significant cytotoxicity in the working
      concentration and more usage of these peptides. In conclusion, we have designed a
      novel transfection-enhancing peptide by easy homodimerization of Tat peptide, and
      the simple mix of these novel peptides with DNA increased the gene transfer of
      cationic lipids more efficiently with no additional cytotoxicity.

PMID- 21876370
TI  - Purification, and biochemical and biophysical characterization of
      cellobiohydrolase I from Trichoderma harzianum IOC 3844.
AB  - Because of its elevated cellulolytic activity, the filamentous fungus Trichoderma
      harzianum has a considerable potential in biomass hydrolysis applications.
      Trichoderma harzianum cellobiohydrolase I (ThCBHI), an exoglucanase, is an
      important enzyme in the process of cellulose degradation. Here, we report an easy
      single-step ion-exchange chromatographic method for purification of ThCBHI and
      its initial biophysical and biochemical characterization. The ThCBHI produced by
      induction with microcrystalline cellulose under submerged fermentation was
      purified on DEAE-Sephadex A-50 media and its identity was confirmed by mass
      spectrometry. The ThCBHI biochemical characterization showed that the protein has
      a molecular mass of 66 kDa and pI of 5.23. As confirmed by smallangle X-ray
      scattering (SAXS), both full-length ThCBHI and its catalytic core domain (CCD)
      obtained by digestion with papain are monomeric in solution. Secondary structure
      analysis of ThCBHI by circular dichroism revealed alpha- helices and beta-strands
      contents in the 28% and 38% range, respectively. The intrinsic fluorescence
      emission maximum of 337 nm was accounted for as different degrees of exposure of
      ThCBHI tryptophan residues to water. Moreover, ThCBHI displayed maximum activity
      at pH 5.0 and temperature of 50 degrees C with specific activities against Avicel
      and p-nitrophenyl-beta-D-cellobioside of 1.25 U/mg and 1.53 U/mg, respectively.

PMID- 21876371
TI  - Isolation and characterization of a novel agarase-producing Pseudoalteromonas
      spp. bacterium from the guts of spiny turban shells.
AB  - An agar-degrading bacterium was isolated from the guts of spiny turban shells. It
      was identified as a Pseudoalteromonas species and named Pseudoalteromonas sp.
      JYBCL 1. The viscosity of the inoculated agar medium decreased by more than 60%
      after 20 h cultivation. The agarase produced by the isolate had optimal
      activities at 35 degrees C and pH 7. The enzyme had extremely strong resistance
      to ionic stress compared with other known agarases. Its molecular mass was
      estimated at about 60 kDa by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis. The agarase could saccharify Gelidium amansii directly, with an
      efficiency about half that compared with agar saccharification.

PMID- 21876372
TI  - Effects of penicillin G on morphology and certain physiological parameters of
      Lactobacillus acidophilus ATCC 4356.
AB  - Evidence shows that probiotic bacteria can undergo substantial structural and
      morphological changes in response to environmental stresses, including
      antibiotics. Therefore, this study investigated the effects of penicillin G
      (0.015, 0.03, and 0.06 mg/l) on the morphology and adhesion of Lactobacillus
      acidophilus ATCC 4356, including the colony morphotype, biofilm production,
      hydrophobicity, H2O2 formation, S-layer structure, and slpA gene expression.
      Whereas only smooth colonies grew in the presence of penicillin, rough and smooth
      colony types were observed in the control group. L. acidophilus ATCC 4356 was
      found to be hydrophobic under normal conditions, yet its hydrophobicity decreased
      in the presence of the antibiotic. No biofilm was produced by the bacterium,
      despite testing a variety of different culture conditions; however, treatment
      with penicillin G (0.015-0.06 mg/l) significantly decreased its production of
      H2O2 formation and altered the S-layer protein structure and slpA gene
      expression. The S-protein expression decreased with 0.015 mg/l penicillin G, yet
      increased with 0.03 and 0.06 mg/l penicillin G. In addition, the slpA gene
      expression decreased in the presence of 0.015 mg/l of the antibiotic. In
      conclusion, penicillin G was able to alter the S-layer protein production, slpA
      gene expression, and certain physicochemical properties of Lactobacillus
      acidophilus ATCC 4356.

PMID- 21876373
TI  - Molecular cloning of maltooligosyltrehalose trehalohydrolase gene from Nostoc
      flagelliforme and trehalose-related response to stresses.
AB  - A genomic DNA fragment encoding a putative maltooligosyltrehalose
      trehalohydrolase (NfMTH) for trehalose biosynthesis was cloned by the degenerate
      primer- PCR from cyanobacterium Nostoc flagelliforme. The ORF of NfMTH is 1,848
      bp in length and encodes 615 amino acid residues, constituting a 70 kDa protein.
      The deduced amino acid sequence of NfMTH contains 4 regions highly conserved for
      MTHs. By expression of NfMTH in E. coli, the function of this protein was
      demonstrated, where the recombinant protein catalyzed the hydrolysis of
      maltooligosyl trehalose to trehalose. The expressions of MTH and
      maltooligosyltrehalose synthase in the filaments of N. flagelliforme were
      upregulated significantly under dehydration stress, NaCl stress, and high
      temperature-drought stress. The accumulations of both trehalose and sucrose in
      the filaments of N. flagelliforme were also improved significantly under the
      above stresses. Furthermore, trehalose accumulated in smaller quantities than
      sucrose did when under NaCl stress, but accumulated in higher quantities than
      sucrose did when under temperature-drought stress, indicating that both trehalose
      and sucrose were involved in N. flagelliforme adapted to stresses and different
      strategies conducted in response to various stress conditions.

PMID- 21876374
TI  - Molecular characterization of bile salt hydrolase from Bifidobacterium animalis
      subsp. lactis Bi30.
AB  - The present work describes the identification, purification, and characterization
      of bile salt hydrolase (BSH) from Bifidobacterium animalis subsp. lactis. The
      enzyme was purified to electrophoretic homogeneity by hydrophobic chromatography,
      ion-exchange chromatography and ultrafiltration. SDS-PAGE analysis of putative
      BSH and gel filtration revealed that the analyzed protein is presumably a
      tetramer composed of four monomers each of about 35 kDa. The purified enzyme was
      analyzed by liquid chromatography coupled to LTQ FT ICR mass spectrometry and
      unambiguously identified as a bile salt hydrolase from B. animalis. The
      isoelectric point of the studied protein was estimated to be around pH 4.9. The
      pH optimum of the purified BSH is between 4.7 to 6.5, and the temperature optimum
      is around 50 degrees C. The BSH of B. animalis could deconjugate all tested bile
      salts, with clear preference for glycine-conjugated bile salts over taurine
      conjugated forms. Genetic analysis of the bsh showed high similarity to the
      previously sequenced bsh gene from B. animalis and confirmed the usefulness of
      bile salt hydrolase as a genetic marker for B. animalis identification.

PMID- 21876375
TI  - Production of 1,2-propanediol from glycerol in Saccharomyces cerevisiae.
AB  - Glycerol has become an attractive carbon source in the biotechnology industry
      owing to its low price and reduced state. However, glycerol is rarely used as a
      carbon source in Saccharomyces cerevisiae because of its low utilization rate. In
      this study, we used glycerol as a main carbon source in S. cerevisiae to produce
      1,2-propanediol. Metabolically engineered S. cerevisiae strains with
      overexpression of glycerol dissimilation pathway genes, including glycerol kinase
      (GUT1), glycerol 3-phosphate dehydrogenase (GUT2), glycerol dehydrogenase (gdh),
      and a glycerol transporter gene (GUP1), showed increased glycerol utilization and
      growth rate. More significant improvement of glycerol utilization and growth rate
      was accomplished by introducing 1,2-propanediol pathway genes, mgs (methylglyoxal
      synthase) and gldA (glycerol dehydrogenase) from Escherichia coli. By engineering
      both glycerol dissimilation and 1,2-propanediol pathways, the glycerol
      utilization and growth rate were improved 141% and 77%, respectively, and a 2.19
      g 1,2- propanediol/l titer was achieved in 1% (v/v) glycerolcontaining YEPD
      medium in engineered S. cerevisiae.

PMID- 21876376
TI  - Optimization of rhamnetin production in Escherichia coli.
AB  - POMT7, which is an O-methyltransferase from poplar, transfers a methyl group to
      several flavonoids that contain a 7-hydroxyl group. POMT7 has been shown to have
      a higher affinity toward quercetin, and the reaction product rhamnetin has been
      shown to inhibit the formation of beta-amyloid. Thus, rhamnetin holds great
      promise for use in therapeutic applications; however, methods for mass production
      of this compound are not currently available. In this study, quercetin was
      biotransformed into rhamnetin using Escherichia coli expressing POMT7, with the
      goal of developing an approach for mass production of rhamnetin. In order to
      maximize the production of rhamnetin, POMT7 was subcloned into four different E.
      coli expression vectors, each of which was maintained in E. coli with a different
      copy number, and the best expression vector was selected. In addition, the S
      adenosylmethionine biosynthesis pathway was engineered for optimal cofactor
      production. Through the combination of optimized POMT7 expression and cofactor
      production, the production of rhamnetin was increased up to 111 mg/l, which is
      approximately 2-fold higher compared with the E. coli strain containing only
      POMT7.

PMID- 21876377
TI  - Replacement of hexachlorocyclohexane to environmentally friendly biosurfactant as
      precursor for the production of biosurfactant from Pseudomonas.
AB  - Production of biosurfactant can be substantially increased by the addition of
      precursors like vegetable oils, petroleum products, and other water-insoluble
      substances. Pseudomonas Ptm+ strain produces biosurfactant in the presence of
      hexachlorocyclohexane (HCH), which specifically emulsifies HCH, a recalcitrant
      organochlorine pesticide. Addition of previously produced crude biosurfactant by
      the same organism as a precursor instead of HCH increased production of
      biosurfactants with a decrease in the total fermentation time from 32 to 24 h.
      The main objective of this paper was to find alternatives for HCH as an inducer.

PMID- 21876378
TI  - Cloning, expression, and characterization of a new xylanase from alkalophilic
      Paenibacillus sp. 12-11.
AB  - A xylanase gene, xyn7c, was cloned from Paenibacillus sp. 12-11, an alkalophilic
      strain isolated from the alkaline wastewater sludge of a paper mill, and
      expressed in Escherichia coli. The full-length gene consists of 1,296 bp and
      encodes a mature protein of 400 residues (excluding the putative signal peptide)
      that belongs to the glycoside hydrolase family 10. The optimal pH of the purified
      recombinant XYN7C was found to be 8.0, and the enzyme had good pH adaptability at
      6.5-8.5 and stability over a broad pH range of 5.0-11.0. XYN7C exhibited maximum
      activity at 55 degrees C and was thermostable at 50 degrees C and below. Using
      wheat arabinoxylan as the substrate, XYN7C had a high specific activity of 1,886
      U/mg, and the apparent Km and Vmax values were 1.18 mg/ml and 1,961 MUmol/mg/min,
      respectively. XYN7C also had substrate specificity towards various xylans, and
      was highly resistant to neutral proteases. The main hydrolysis products of xylans
      were xylose and xylobiose. These properties make XYN7C a promising candidate to
      be used in biobleaching, baking, and cotton scouring processes.

PMID- 21876379
TI  - Submerged monoxenic culture medium development for Heterorhabditis bacteriophora
      and its symbiotic bacterium Photorhabdus luminescens: protein sources.
AB  - Most medium formulations for improving culture of entomopathogenic nematodes
      (EPN) based on protein sources have used enriched media like animal feed such as
      dried egg yolk, lactalbumin, and liver extract, among other ingredients. Most
      results, however, showed unstable yields and longer production time. Many of the
      results do not show the detailed parameters of fermentation. Soy flour, cotton
      seed flour, corn gluten meal, casein powder, soytone, peptone, casein
      hydrolysates, and lactalbumin hydrolysate as protein sources were tested to
      determine the source to support optimal symbiotic bacteria and nematode growth.
      The protein hydrolysates selected did not improve bacterial cell mass compared
      with the yeast extract control, but soy flour was the best, showing 75.1%
      recovery and producing more bacterial cell number (1.4*109/ml) than all other
      sources. The highest yield (1.85*105 IJs/ml), yield coefficient (1.67*106 IJs/g
      medium), and productivity (1.32*107 IJs/l/day) were also achieved at enriched
      medium with soybean protein.

PMID- 21876380
TI  - Rehmannia glutinosa ameliorates scopolamine-induced learning and memory
      impairment in rats.
AB  - Many studies have shown that the steamed root of Rehmannia glutinosa (SRG), which
      is widely used in the treatment of various neurodegenerative diseases in the
      context of Korean traditional medicine, is effective for improving cognitive and
      memory impairments. The purpose of this study was to examine whether SRG extracts
      improved memory defects caused by administering scopolamine (SCO) into the brains
      of rats. The effects of SRG on the acetylcholinergic system and proinflammatory
      cytokines in the hippocampus were also investigated. Male rats were administered
      daily doses of SRG (50, 100, and 200 mg/kg, i.p.) for 14 days, 1 h before
      scopolamine injection (2 mg/kg, i.p.). After inducing cognitive impairment via
      scopolamine administration, we conducted a passive avoidance test (PAT) and the
      Morris water maze (MWM) test as behavioral assessments. Changes in cholinergic
      system reactivity were also examined by measuring the immunoreactive neurons of
      choline acetyltransferase (ChAT) and the reactivity of acetylcholinesterase
      (AchE) in the hippocampus. Daily administration of SRG improved memory impairment
      according to the PAT, and reduced the escape latency for finding the platform in
      the MWM. The administration of SRG consistently significantly alleviated memory
      associated decreases in cholinergic immunoreactivity and decreased interleukin
      1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) mRNA expression in
      the hippocampus. The results demonstrated that SRG had a significant
      neuroprotective effect against the neuronal impairment and memory dysfunction
      caused by scopolamine in rats. These results suggest that SRG may be useful for
      improving cognitive functioning by stimulating cholinergic enzyme activities and
      alleviating inflammatory responses.

PMID- 21876381
TI  - DUSPs strike again.

PMID- 21876383
TI  - A non-specific effect of orally administered Escherichia coli.
AB  - A number of genetically modified bacteria able to deliver a therapeutic gene into
      target cells has already been tested. Apart from the expected effects of
      bacterial therapy, the therapeutic bacterial strain also mediates a non-specific
      effect independent of the gene to be delivered. In this regard, we have recently
      shown that oral administration of the bacterial strain Escherichia coli XL1-Blue
      via gastric gavage to rats leads to a non-specific decrease in expression of
      vascular endothelial growth factor (VEGF) in intestinal wall without
      corresponding changes in other parameters. We tried to adopt a model of
      intestinal ischemia and to treat the subsequent hypoxic condition using a strain
      carrying the effector plasmid encoding hypoxia-inducible factor 1 alpha (HIF
      1alpha), as well as the helper plasmid encoding invasion and listeriolysin O.
      However, the model was ineffective, as obvious from macroscopic and molecular
      observations. We hypothesize that a competitive behavior of the administered
      strain in the intestinal microbiota leads to a decrease in activity of HIF-1alpha
      and reduction in expression of VEGF. Also, a functional disease model would be
      necessary for the invasion-expressing therapeutic strain to be effective. A
      different approach using bacterial protein delivery would possibly circumvent
      these bactofection-related problems.

PMID- 21876382
TI  - The toxin and antidote puzzle: new ways to control insect pest populations
      through manipulating inheritance.
AB  - Insects carry out essential ecological functions, such as pollination, but also
      cause extensive damage to agricultural crops, and transmit human diseases such as
      malaria and dengue fever. Advances in insect transgenesis are making it
      increasingly feasible to engineer genes conferring desirable phenotypes, and gene
      drive systems are required to spread these genes into wild populations. Medea
      provides one solution, being able to spread into a population from very low
      initial frequencies through the action of a maternally-expressed toxin linked to
      a zygotically-expressed antidote. Several other toxin-antidote combinations are
      imaginable that distort the offspring ratio in favor of a desired transgene, or
      drive the population towards an all-male crash. We explore two such systems-
      Semele, which is capable of spreading a desired transgene into an isolated
      population in a confined manner; and Merea, which is capable of inducing a local
      population crash when located on the Z chromosome of a Lepidopteron pest.

PMID- 21876384
TI  - Anti-mycobacterial peptides: made to order with delivery included.
AB  - "TB is too often a death sentence. It does not have to be this way,"- Nelson
      Mandela. Despite the success of anti-mycobacterial drugs over the past 70 years,
      mycobacterial disease, particularly tuberculosis is still responsible for
      millions of annual deaths worldwide. Additionally, the emergence of Multidrug
      Resistant (MDR-TB) and Extensively Drug Resistant (XDR-TB) Tuberculosis has
      motivated calls by the World Health Organization (WHO) for novel drugs, vaccines
      and diagnostic tests. Consequently, the identification and evaluation of a range
      of anti-mycobacterial compounds against pathogenic mycobacterial species is of
      paramount importance. My colleagues and I at Cork Institute of Technology (CIT)
      and University College Cork (UCC) have tackled this issue through the initial
      optimization of the rapid, robust and inexpensive microtitre alamarBlue assay
      (MABA) and subsequent employment of this assay to facilitate the rapid assessment
      of a new wave of potential therapeutic compounds, namely bacteriocins, in
      particular type 1 bacteriocins known as lantibiotics. The gene encoded nature of
      these peptides facilitates their genetic manipulation and consequent activities
      as anti-microbial agents. In this regard, it may be possible to one day develop
      diverse populations of anti-mycobacterial bacteriocins with species specific
      activities. This may in turn provide more targeted therapies, resulting in less
      side effects, shorter treatment times and thus better patient compliance.
      Although current drug regimes are effective in the interim, previous lessons have
      taught us not to be complacent. In the words of the Intel founder Andrew Grove,
      'Success breeds complacency. Complacency breeds failure. Only the paranoid
      survive'. Armed with knowledge of previous failures, it is the duty of the
      scientific community to anticipate future bacterial resistance and have an
      arsenal of compounds standing by in such an eventuality.

PMID- 21876385
TI  - Processing of homologous recombination repair intermediates by the Sgs1-Top3-Rmi1
      and Mus81-Mms4 complexes.
AB  - Homologous recombination repair (HRR) is an evolutionarily conserved cellular
      process that is important for the maintenance of genome stability during S phase.
      Inactivation of the Saccharomyces cerevisiae Sgs1-Top3-Rmi1 complex leads to the
      accumulation of unprocessed, X-shaped HRR intermediates (X structures) following
      replicative stress. Further characterization of these X structures may reveal why
      loss of BLM (the human Sgs1 ortholog) leads to the human cancer predisposition
      disorder, Bloom syndrome. In two recent complementary studies, we examined the
      nature of the X structures arising in yeast strains lacking Sgs1, Top3 or Rmi1 by
      identifying which proteins could process these structures in vivo. We revealed
      that the unprocessed X structures that accumulate in these strains could be
      resolved by the ectopic overexpression of two different Holliday junction (HJ)
      resolvases, and that the endogenous Mus81-Mms4 endonuclease could also remove
      them, albeit slowly. In this review, we discuss the implications of these results
      and review the putative roles for the Sgs1-Top3-Rmi1 and Mus81-Mms4 complexes in
      the processing of various types of HRR intermediates during S phase.

PMID- 21876387
TI  - A proteolytic cleavage assay to monitor autophagy in Dictyostelium discoideum.
AB  - Dictyostelium discoideum is a good model of autophagy. However, the lack of
      autophagic flux techniques hinders the assessment of new mutants or drugs. One of
      these techniques, which has been used successfully in yeast and mammalian cells,
      but has not yet been described in Dictyostelium, is based on the presence of
      proteolytic fragments derived from autophagic degradation of expressed fusion
      proteins. Lysosomotropic agents such as NH 4Cl penetrate acidic compartments and
      raise their pH, thus allowing the accumulation and measurement of these cleaved
      fragments, which otherwise would be rapidly degraded. We have used this property
      to detect the presence of free GFP fragments derived from the fusion protein GFP
      Tkt-1, a cytosolic marker. We demonstrate that this proteolytic event is
      dependent on autophagy and can be used to detect differences in the level of
      autophagic flux among different mutant strains. Moreover, treatment with NH4Cl
      also facilitates the assessment of autophagic flux by confocal microscopy using
      the marker RFP-GFP-Atg8.

PMID- 21876388
TI  - Ten years after 9/11: what have we (not yet) learned?

PMID- 21876389
TI  - Skin tears: state of the science: consensus statements for the prevention,
      prediction, assessment, and treatment of skin tears(c).
AB  - The appropriate management of patients with skin tears is an ongoing challenge
      for healthcare professionals. Skins tears are often painful, acute wounds
      resulting from trauma to the skin and are largely preventable. Healthcare
      professionals must be able to identify individuals at risk for skin tears and aid
      in the prevention of these wounds and in their treatment when they occur. Despite
      preliminary studies that suggest skin tears may be more prevalent than pressure
      ulcers, there remains a paucity of literature to guide prevention, assessment,
      and treatment of skin tears. As a result, these wounds are often mismanaged and
      misdiagnosed, leading to complications, including pain, infection, and delayed
      wound healing. In addition, skin tears increase caregiver time and facility
      costs, cause anxiety for patients and families, and may reflect poorly on the
      quality of care delivered in a facility. In an effort to shift awareness toward
      this largely unheeded healthcare issue, a consensus panel of 13 internationally
      recognized key opinion leaders convened to establish consensus statements on the
      prevention, prediction, assessment, and treatment of skin tears. The initial
      consensus panel meeting was held in January 2011 and was made possible by an
      unrestricted educational grant from Hollister Wound Care. This document details
      the consensus definition and statements, as well as recommendations for future
      research and steps toward establishing a validated, comprehensive program for
      managing skin tears.

PMID- 21876390
TI  - Immune reconstitution inflammatory syndrome following cryptosporidial
      cholangitis.

PMID- 21876386
TI  - Roles of COP9 signalosome in cancer.
AB  - The constitutive photomorphogenesis 9 signalosome (COP9 or CSN) is an
      evolutionarily conserved multiprotein complex found in plants and animals.
      Because of the homology between the COP9 signalosome and the 19S lid complex of
      the proteosome, COP9 has been postulated to play a role in regulating the
      degradation of polyubiquitinated proteins. Many tumor suppressor and oncogene
      products are regulated by ubiquitination- and proteosome-mediated protein
      degradation. Therefore, it is conceivable that COP9 plays a significant role in
      cancer, regulating processes relevant to carcinogenesis and cancer progression
      (e.g., cell cycle control, signal transduction and apoptosis). In mammalian
      cells, it consists of eight subunits (CSN1 to CSN8). The relevance and importance
      of some subunits of COP9 to cancer are emerging. However, the mechanistic
      regulation of each subunit in cancer remains unclear. Among the CSN subunits,
      CSN5 and CSN6 are the only two that each contain an MPN (Mpr1p and Pad1p N
      terminal) domain. The deneddylation activity of an MPN domain toward cullin-RING
      ubiquitin ligases (CRL) may coordinate CRL-mediated ubiquitination activity. More
      recent evidence shows that CSN5 and CSN6 are implicated in ubiquitin-mediated
      proteolysis of important mediators in carcinogenesis and cancer progression.
      Here, we discuss the mechanisms by which some CSN subunits are involved in cancer
      to provide a much needed perspective regarding COP9 in cancer research, hoping
      that these insights will lay the groundwork for cancer intervention.

PMID- 21876391
TI  - Could we, should we? Yes.

PMID- 21876392
TI  - Creating effective electronic medical record change management processes.

PMID- 21876393
TI  - Hitech: regional extension centers: an example from Minnesota and North Dakota.

PMID- 21876394
TI  - Comparison of social support content within online communities for high- and low
      survival-rate cancers.
AB  - People experiencing cancer use the Internet for many reasons, particularly for
      social support. This study sought to determine how social support content within
      online support communities for different cancers varied according to cancer
      survival rate. A quantitative content analysis was conducted on 3717 posts from
      eight online communities focused on cancers with high and low 5-year relative
      survival rates. Using Optimal Matching Theory, we predicted that low-survival
      rate communities would have more emotional support content than high-survival
      rate communities, and high-survival-rate communities would have more
      informational support content than low-survival-rate communities. Emotional
      support content was consistently more common than informational support. Overall,
      high-survival-rate communities had a greater proportion of posts containing
      emotional support content (75%) than low-survival-rate communities (66%) (chi1 =
      20.89 [n = 2235], P < .001). Furthermore, low-survival-rate communities had a
      greater proportion of posts containing informational support content (46%) than
      high-survival-rate communities (36%) (chi1 = 21.13 [n = 2235], P< .001). Although
      the relationships between survival rate and support types were significant, they
      were not as hypothesized. Deviations from theoretically predicted results suggest
      that individuals experiencing low-survival-rate cancers may have a greater desire
      for informational support online than individuals experiencing high-survival-rate
      cancers.

PMID- 21876396
TI  - Progress and publication ethics.

PMID- 21876397
TI  - Detection of unsuspected bone metastases by 68Ga-DOTA: nuclear medicine at the
      forefront again.

PMID- 21876398
TI  - Nuclear medicine techniques in the assessment of alkaptonuria.
AB  - Alkaptonuria is a rare autosomal recessive disorder due to a lack of the enzyme
      homogentisate dioxygenase, leading to ochronosis, a process of accumulation of a
      melanin-like polymer of homogentisic acid in cartilage and other collagenous
      structures. Patients develop severe osteoarthropathy that resembles
      osteoarthritis. Although the diagnosis of alkaptonuria is not particularly
      challenging in view of the blue-black discolouration of visible connective tissue
      and the presence of homogentisic acid in urine, the natural history of
      alkaptonuria remains poorly understood. Patients would benefit immensely from an
      objective assessment of their disease status and from a clearer understanding of
      the pathophysiology and associated physical changes. Isotope bone scans, which
      are commonly used to identify the extent of involvement of bones in cancerous
      processes, have also been increasingly used for characterizing the extent of
      arthropathy in conditions such as osteoarthritis and rheumatoid arthritis.
      Semiquantitative scores based on the extent of involvement of joints have been
      used to describe the involvement of large joints in the context of symptomatic
      treatment for osteoarthritis. A similar semiquantitative isotope bone scan score
      depending on the involvement of the number of large joints in patients with
      alkaptonuria can be formulated and validated in a suitable cohort of patients.
      Bone densitometry measurement using dual-energy X-ray absorptiometry scanning is
      an internationally accepted tool to assess the risk and extent of osteoporosis,
      and is increasingly used to assess the additional fracture risk in patients with
      arthropathy. We believe that, currently, nuclear medicine techniques can provide
      useful information, which can be incorporated into disease severity scores for
      alkaptonuria. Once the biological basis for alkaptonuria is better understood, it
      is feasible that nuclear medicine techniques of even greater sensitivity and
      specificity can be developed, thereby taking advantage of the vast advances in
      the fields of radiochemistry, radiopharmacy, positron emission tomography
      computed tomography and positron emission tomography-magnetic resonance imaging
      scanning.

PMID- 21876399
TI  - Radiolabelling of peptides for PET, SPECT and therapeutic applications using a
      fully automated disposable cassette system.
AB  - OBJECTIVES: Radiolabelled somatostatin analogues have found wide clinical use in
      nuclear medicine for both diagnostic and therapeutic applications. Here, we
      describe the development of a fully automated synthesis system allowing
      radiolabelling of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)
      derivatized peptides with 68Ga/111In/177Lu and 90Y, meeting radiation safety and
      pharmaceutical requirements. MATERIALS AND METHODS: The system consists of a
      syringe pump, a holder for insertion of a single use multivalve cassette, a
      heater and a removable radiation shielding. 68Ga labelling was performed in
      acetate buffer and 177Lu, 90Y and 111In labelling in ascorbate buffer,
      respectively, followed by purification on a C18 cartridge and final sterile
      filtration. Cross-contamination was prevented by using disposable cassettes and
      also by ensuring pharmaceutical standards. Radiochemical purity (RCP) was
      determined by instant thin-layer chromatography on silica gel impregnated glass
      fibres and reversed-phase high performance liquid chromatography. RESULTS: 68Ga
      DOTA-peptides were prepared with high RCP (>91%) and radiochemical yields
      (RCY>80% decay corrected) and 68Ge content was less than 0.0001% in all cases.
      Synthesis time did not exceed 30 min. 111In, 177Lu and 90Y labelling of DOTA
      peptides resulted again in high yields (approximately 90%) and RCP (approximately
      95%) and total synthesis time of less than 45 min. Radiation dose to fingers was
      considerably reduced when compared with manual labelling procedures. CONCLUSION:
      The described system allows fully automated, aseptic preparation of DOTA-peptides
      radiolabelled with different radionuclides in high radiochemical yields and
      pharmaceutical quality suitable for clinical application.

PMID- 21876401
TI  - The value of positron-emission tomography/computed tomography for radiotherapy
      treatment planning: a single institutional series.
AB  - BACKGROUND: This study aimed to compare the clinical target volumes (CTV)
      delineated by computed tomography (CT) and positron emission tomography (PET)/CT
      using fluoro-deoxy-glucose to assess the impact of using PET information for
      radiotherapy (RT) planning. METHODS: We retrospectively reviewed data on patients
      with tumors from different sites who had indications for RT and had undergone RT
      treatment planning with PET/CT at our institution between July 2003 and July
      2009. Statistical analysis included the comparison of CTV planned for treatment
      only by CT (CTV(CT)) with that by PET/CT (CTV(PET)) using the Wilcoxon test for
      paired samples. RESULTS: Of 105 patients eligible for analysis, 56.2% were men.
      The most common diagnoses were head and neck cancer (28.6%), lung cancer (21.9%),
      lymphoma (11.4%), upper gastrointestinal (10.5%), and others (14.3%). Comparison
      of CTV(CT) and CTV(PET) revealed that RT planning has changed in 77% of cases
      because of PET/CT additional information, with impact on treatment volume varying
      according to diagnosis. Despite the absolute difference observed between median
      CTVs, there was no significant difference between CTV(CT) and CTV(PET) (114 vs.
      90.4 ml, respectively; P=0.1266), considering all patients. Nonetheless, a
      significant difference between CTVs delineated by CT and PET/CT was found when
      only head and neck, lung and lymphoma cases--representing more than 60% of the
      sample--were examined (112.5 and 80.7 ml, respectively; P=0.0053). CONCLUSION: We
      have shown that PET/CT use promotes significant changes in the CTV delineated for
      treatment of different tumors, modifying RT planning. Our data suggest that
      PET/CT has a good potential for optimizing RT treatment planning, especially in
      head and neck, lung, and lymphoma tumors.

PMID- 21876400
TI  - Quantification of the neurokinin 1 receptor ligand [11C]R116301.
AB  - PURPOSE: Neurokinin 1 (NK1) receptors have been implicated in depression,
      anxiety, and pain perception. Recently, it was shown that, in the human brain, a
      specific NK1 receptor-related signal was obtained with the novel radioligand,
      [11C]R116301, using positron emission tomography. The purpose of this study was
      to evaluate various methods for quantifying specific [11C]R116301 binding.
      METHODS: Two dynamic 90-min [11C]R116301 scans, separated by 5 h, were performed
      in 11 healthy volunteers. In three patients, the second scan was performed after
      an oral blocking dose of 125 mg of aprepitant, whereas in the other eight, no
      intervention was performed (test-retest). Whole striatum was used as the tissue
      of interest, as it has the highest density of NK1 receptors. Cerebellum was used
      as the reference tissue. RESULTS: Reference tissue models were stable with the
      simplified reference tissue model (SRTM) performing best. Average (+/- standard
      deviation) SRTM-derived mean nondisplaceable binding potential (BP(ND)) of all
      (first) baseline scans was 0.64+/-0.31 (n=11), which reduced to -0.01+/-0.03
      (n=3) after aprepitant administration. Test-retest results showed low variability
      (14.0+/-10.7%) and excellent reliability, as indicated by the intraclass
      correlation coefficient (0.93). The ratio of standardized uptake values of
      striatum and cerebellum minus 1, an approximation of BP(ND), showed very low
      variability (6.2+/-3.1%) with excellent reliability (intraclass correlation
      coefficient=0.98), and correlated well with SRTM-derived BP(ND) (R2=0.96).
      CONCLUSION: SRTM is the model of choice for quantifying [11C]R116301 binding.
      Semiquantitative tissue ratios hold promise for routine clinical applications.

PMID- 21876402
TI  - Renogram comparison of p-[(18)F]fluorohippurate with o-[(125)I]iodohippurate and
      [(99m)Tc]MAG3 in normal rats.
AB  - OBJECTIVE: We recently identified p-[(18)F]fluorohippurate ([(18)F]PFH) as a
      potential positron emission tomography (PET) renal agent. The objective of this
      study was to compare renogram parameters of [(18)F]PFH with o
      [(125)I]iodohippurate ([(125)I]OIH) as a surrogate for the renal imaging gold
      standard (131)I-OIH and with a clinically used agent [(99m)Tc]MAG3. METHODS:
      Normal Sprague-Dawley rats (n=4) were sequentially imaged on days 1, 2, and 3
      using [(99m)Tc]MAG3 (18.1-19.1 MBq, dynamic planar), [(18)F]PFH (2.6-4.1 MBq,
      dynamic PET), and [(125)I]OIH (7.7-13.5 MBq, dynamic planar), respectively. The
      PET data were binned into frames of 30 s each, whereas the planar images were
      acquired as 30 s per frame. Regions of interest were drawn on both kidneys, and
      decay-corrected renograms were generated for each imaging modality. RESULTS: The
      PET-derived [(18)F]PFH renograms revealed an average time-to-peak (T(max)) of
      4.8+/-2.4 min, which was comparable to the T(max) of 3.6+/-1.7 min and 4.3+/-1.7
      min for [(125)I]OIH and [(99m)Tc]MAG3 renograms, respectively. The average time
      to-half-maximal activity was found to be 16.6+/-6.6 min, 8.3+/-2.4 min, and more
      than 20 min with [(18)F]PFH, [(125)I]OIH, and [(99m)Tc]MAG3, respectively.
      CONCLUSIONS: Compared with [(99m)Tc]MAG3, the renogram parameters of [(18)F]PFH
      seem to be closer to those obtained from [(125)I]OIH. The quality of the renogram
      and the images obtained with the dynamic [(18)F]PFH PET study were remarkably
      better than those obtained with the [(99m)Tc]MAG3 dynamic planar imaging study.

PMID- 21876403
TI  - Comparing two TAG-72 binding peptides previously identified by phage display as
      potential imaging agents.
AB  - AIM: To evaluate the targeting property in vitro and in vivo of two tumor
      associated glycoprotein 72 (TAG-72) binding peptides, previously identified in
      this laboratory by phage selection using different elution conditions. MATERIALS
      AND METHODS: The peptides GGVSCMQTSPVCENNL (A2-6) and NPGTCKDKWEICLLNGG (A3-10)
      were radiolabeled with technetium-99m ((99m)Tc) using N-hydroxysuccinimidyl-S
      acetyl-mercaptoacetyltriglycine (NHS-MAG(3)) as a chelator or were biotinylated.
      The specificity of the two peptides for the TAG-72 positive LS-174T cancer cells
      was demonstrated in vitro both by flow cytometry analysis using the biotinylated
      peptides and by competitive binding using the (99m)Tc-labeled peptides. The in
      vivo biodistributions of the peptides were evaluated in TAG-72 positive LS-174T
      tumor-bearing mice by small-animal single photon emission computed
      tomography/computed tomography imaging. RESULTS: As evidence of specific binding,
      both peptides showed a significant increase in percentage binding with increasing
      peptide concentration by flow cytometry analysis to LS-174T cells, but not to TAG
      72 negative HT-29 cells. The (99m)Tc-labeled A2-6 peptide bound LS-174T cells
      with an inhibition constant at 50% of 46.5 nmol/l compared with 420 nmol/l for
      the A3-10 peptide. In mice, accumulation of both peptides was highest in kidneys
      and gallbladder. Tumors were clearly visible by single photon emission computed
      tomography imaging for both (99m)Tc-labeled peptides through 60 min, although the
      tumor accumulation was higher for the A3-10 peptide. CONCLUSION: The A3-10
      peptide, with lower, yet reasonable binding affinity compared with the A2-6
      peptide, showed sufficiently favorable specific binding and tumor accumulation to
      be considered further as a potential imaging agent for TAG-72 positive cancers.

PMID- 21876404
TI  - Cut-off value for normal versus abnormal right-to-left shunt percentages using
      (99m)Tc-macroaggregated albumin.
AB  - OBJECTIVE: To determine the cut-off value for distinguishing a normal versus an
      abnormal right-to-left shunt percentage on lung perfusion scintigraphy using
      (99m)Tc-macroaggregated albumin (MAA). MATERIALS AND METHODS: Fifty-three
      patients (eight patients with a right-to-left shunt and 45 without a right-to
      left shunt) who underwent MAA whole-body imaging for the evaluation of right-to
      left shunts were divided into group 1 (eight patients with brain MAA uptake) and
      group 2 (45 patients without brain MAA uptake). Moreover, group 2 was subdivided
      into two categories (groups 2a and 2b) based on the results of lung computed
      tomography, electrocardiography examinations, and pulmonary function tests. The
      average and standard deviation (SD) of each group were compared. In addition, we
      estimated the cut-off value for a normal right-to-left shunt percentage using
      whole-body imaging. RESULTS: The average right-to-left shunt percentage values
      and SD were 23.67+/-12.17% in group 1, 6.68+/-1.04% in group 2a, and 6.60+/-0.84%
      in group 2b. The shunt percentages of groups 2a and 2b were not significantly
      different (P=0.77). The estimated normal value (mean+/-2 SD) of group 2 was
      6.64+/-0.94%. Meanwhile, the cut-off value was estimated as 10% based on the
      distributions of MAA shunt percentages for groups 1 and 2. CONCLUSION: The normal
      range (mean+/-2 SD) was 6.64+/-1.88%. The cut-off value for the normal right-to
      left shunt percentage in MAA scintigraphy was 10%.

PMID- 21876405
TI  - Low-dose (123)I-metaiodobenzylguanidine diagnostic scan is inferior to (131)I
      metaiodobenzylguanidine posttreatment scan in detection of malignant
      pheochromocytoma and paraganglioma.
AB  - OBJECTIVE: We assessed the lesion detectability of low-dose diagnostic (123)I
      metaiodobenzylguanidine (MIBG) whole-body scans obtained at 6 and 24 h compared
      with posttreatment (131)I-MIBG whole-body scans in malignant pheochromocytoma and
      paraganglioma. METHODS: Scintigrams obtained in 15 patients with malignant
      pheochromocytoma and paraganglioma were retrospectively analyzed. Diagnostic
      scans were performed with 111 MBq of (123)I-MIBG. Therapeutic doses of (131)I
      MIBG (5.55-7.40 GBq) were administrated and whole-body scans were obtained at 2-5
      days after (131)I-MIBG administrations. We compared the number of lesions and the
      lesion-to-referent count ratios at 6 and 24 h of (123)I-MIBG and at 2-5 days of
      (131)I-MIBG. RESULTS: In comparison with the 6-h images of (123)I-MIBG, the 24-h
      images of (123)I-MIBG could detect more lesions in eight patients. Posttreatment
      (131)I-MIBG scans revealed new lesions in eight patients compared with the 24-h
      images of (123)I-MIBG. The lesion-to-referent count ratios at 6 and 24 h of
      (123)I-MIBG and at 3 days of (131)I-MIBG were increasing at later scanning time.
      There were significant differences in the lesion-to-referent count ratios between
      6 and 24 h of (123)I-MIBG (P = 0.031), 6 h of (123)I-MIBG and 3 days of (131)I
      MIBG (P = 0.020), and 24 h of (123)I-MIBG and 3 days of (131)I-MIBG (P = 0.018).
      CONCLUSION: Low-dose diagnostic (123)I-MIBG whole-body scan is inferior to
      posttreatment (131)I-MIBG whole-body scan in malignant pheochromocytoma and
      paraganglioma. Considering the scan timing of (123)I-MIBG, 6-h images might have
      no superiority compared with 24-h images.

PMID- 21876406
TI  - Personnel exposure in labelling and administration of (177)Lu-DOTA-D-Phe1-Tyr3
      octreotide.
AB  - OBJECTIVE: The introduction of peptide receptor radionuclide therapy, mainly
      performed with (90)Y and (177)Lu-labelled somatostatin analogues, has widened the
      therapeutic horizon of nuclear medicine.The handling of (177)Lu-labelled
      pharmaceuticals implies an increase of the personnel exposure and this aspect is
      evaluated in this paper, in comparison with personal exposure in (90)Y
      manipulation. MATERIALS AND METHODS: Personal dose measurements were performed
      during 26 (177)Lu-DOTATOC preparations by using a series of thin active layer
      LiF: Mg,Cu,P thermoluminescence dosimeters fixed at the operator's fingertips to
      evaluate the skin equivalent dose and by means of direct reading dosimeters
      positioned at the chest to evaluate the personal effective dose. Individual
      protection devices, such as shielded aprons and anti-X gloves, were also used.
      RESULTS: The 95th percentile of the skin equivalent dose distribution for (177)Lu
      operations by using 0.20-mm anti-X gloves was 0.080 mSv/GBq for the chemist and
      0.011 mSv/GBq for the physician, whereas the 75th percentile was 0.058 mSv/GBq
      for the chemist and 0.006 mSv/GBq for the physician. The use of the 0.25 mm Pb
      equivalent anti-X apron halved the personal equivalent dose measured over the
      apron by a direct reading dosimeter. Skin doses were compared with (90)Y-DOTATOC
      procedures: no relevant exposure reduction is observed for chemists, whereas
      doses are considerably lower during administration procedures performed by
      physicians. CONCLUSION: In this study, an evaluation of the skin equivalent doses
      during (177)Lu-DOTATOC labelling and administration is presented. These data can
      be useful to assess the risk for workers in centres that are starting to
      implement PRRT using (177)Lu. The use of appropriate protection devices and
      procedures allows the observance of International Commission for Radiological
      Protection dose limits for exposed workers.

PMID- 21876407
TI  - Measuring SeHCAT retention: a technical note.
AB  - TauroH-23-((75)Se)selena-25-homocholic acid (SeHCAT) retention has been used for
      the diagnosis of bile acid malabsorption since the early 1980s. Bile acid
      malabsorption has been increasingly recognized as an important cause of severe
      chronic diarroea with subsequent increase in the number of referrals for the
      SeHCAT test. In this study, we review and discuss the standard techniques for the
      measurement of SeHCAT retention and describe a simple and modified technique
      using a noncollimated whole-body scanner, suitable for most modern dual-headed
      cameras.

PMID- 21876409
TI  - Accessing your journal online.

PMID- 21876410
TI  - Because you care.

PMID- 21876412
TI  - The role of professional nursing organizations in maintaining a healthy
      workplace.
AB  - This article discusses how professional nursing organizations contribute to the
      goal of a healthy nursing practice environment through offering continuing
      education, developing practice standards, and promoting nursing competence
      through certifications.

PMID- 21876413
TI  - Breast augmentation: motives and the role of the family nurse practitioner.
AB  - Humans tend to compare themselves to their surrounding culture's idea of beauty.
      As a result of the influence exerted by the mass media, the American woman's
      breast is closely linked to womanhood; the fuller the woman's bosom, the sexier
      and more womanly she feels, or is perceived to be by individuals of both sexes.
      Because of these cultural expectations, small-breasted women often experience
      feelings of inadequacy compared with their larger-breasted counterparts, and may
      seek methods of increasing their breast size, such as breast augmentation. An
      estimated 5 million to 7 million women have opted to have this elective surgery
      since its development in 1963. In 2009, nearly 300,000 women chose to undergo
      breast augmentation--an increase of 36% from 2000, and an impressive 787% since
      1992, when the American Society of Plastic Surgeons began formulating yearly
      national cosmetic surgical statistics. These statistical findings reveal that a
      significant number of women are interested in this topic, and health care
      providers need an operational understanding of what is influencing these women's
      health care decisions. As a result of this need, the motives for breast
      augmentation have been researched and classified as either internal or external.
      Internal motives include low levels of self-esteem, body image dissatisfaction,
      and body dysmorphic disorder, whereas external motives are the desire to attract
      and retain a romantic partner, pressures from others, and occupational
      requirements. Understanding these motives allows primary care nurse practitioners
      to focus their assessments on these areas and to provide the appropriate
      counseling or referrals as needed.

PMID- 21876414
TI  - The basics of a health assessment.
AB  - Achieving a good aesthetic result begins with a careful preoperative health
      history and assessment of the patient's desired surgical outcome. Proper
      interview skills provide the foundation for deciding whether a patient is a good
      candidate for surgery, identifying risks, and ensuring an optimal surgical
      experience.

PMID- 21876415
TI  - Malignant melanoma.
AB  - "Melanoma has become a major public health problem worldwide and its incidence in
      individuals of European origin continues to rise. Melanoma is the third most
      common cancer in Australia (in men and women); the fifth in the United States (in
      men and women); and the 12th in men and the sixth in women in the United Kingdom"
      (J. G. Thompson, R. A. Scolyer, & R. F. Kefford, 2009, p. 362). The American
      Cancer Society estimated that about 68,720 new melanomas were diagnosed in the
      United States during 2009, resulting in about 8,650 deaths. The purpose of this
      article is to explain the pathophysiologic components of malignant melanoma.

PMID- 21876416
TI  - Acute coronary syndrome--Part III.

PMID- 21876418
TI  - The hydroquinone debate.

PMID- 21876419
TI  - The biofilm challenge: breaking down the walls.

PMID- 21876420
TI  - Implications of postsurgical pain mismanagement.

PMID- 21876421
TI  - Hiring the right person for the job.

PMID- 21876422
TI  - Mohs micrographic surgery: reconstruction and nursing considerations for
      nonmelanoma skin cancers.

PMID- 21876423
TI  - Understanding the risks and prevention of skin cancer.

PMID- 21876425
TI  - Psychosocial interventions for mental disorders in late life:  are we making
      progress toward efficiency and impact?

PMID- 21876426
TI  - Implantation of mesenchymal stem cells improves right ventricular impairments
      caused by experimental pulmonary hypertension.
AB  - INTRODUCTION: Pulmonary hypertension (PH) is a rapidly progressive and fatal
      disease. In recent years, despite drug treatment made significant progress, the
      prognosis of patients with advanced PH remains extremely poor. The authors
      implanted bone marrow-derived mesenchymal stem cells (BMSCs) intravenously into
      the PH model rats and observed the effect of MSCs on right ventricular (RV)
      impairments. METHODS: BMSCs were isolated, cultured from bone marrow of rats and
      stained with the cross-linkable membrane dye in vitro. One week after, a PH model
      was induced by subcutaneous injection of monocrotaline, the animals were randomly
      divided into 4 groups (n = 20 in each group): I, control; II, MSCs implantation;
      III, PH and IV, PH + MSCs implantation. Two weeks after MSCs implantation, the
      authors observed the MSC survival and transformation by immunofluorescence
      microscopy. On the other hand, RV hypertrophy and the elevation of systolic
      pressure were detected by echocardiography. RESULT: Three weeks after
      monocrotaline injection, RV systolic pressure, mean right ventricular pressure
      and mean pulmonary arterial pressure were significantly elevated in group III
      than in group I and II (P < 0.05) but significantly lower in group IV than in
      group III (P < 0.05). These results showed that implantation of MSCs could
      improve RV impairments caused by experimental PH. Histochemical results confirmed
      that transplanted MSCs were still alive after 2 weeks and part of the cells could
      differentiate into pulmonary vascular endothelial cells. CONCLUSION: Intravenous
      implantation of MSCs could significantly reduce or even reverse the progression
      of MCT-induced PH, improve cardiac function and hemodynamics.

PMID- 21876427
TI  - Prediction of mortality in community-acquired pneumonia in hospitalized patients.
AB  - INTRODUCTION: Community-acquired pneumonia (CAP) is common and associated with a
      significant mortality. Currently recommended criteria to assess severity of CAP
      could be improved. METHODS: We derived 2 new criteria CARSI [confusion, age (<65,
      >=65 to <85 or>= 85), respiratory rate and shock index] and CARASI, where shock
      index is replaced by temperature-adjusted shock index based on previous
      observations. By using data of a prospective study performed in Norfolk and
      Suffolk, United Kingdom, we compare these new indices with the CURB-65 criteria.
      RESULTS: A total of 190 patients were included (men, 53%). The age range was 18
      to 101 years (median, 76 years). There were a total of 54 deaths during a 6-week
      follow-up, all within 30 days of admission. Sixty-five (34%) had severe pneumonia
      by CURB-65. Using CARSI and CARASI, 39 (21%) and 36 (19%) had severe pneumonia,
      respectively. Sensitivity was slightly less, but specificity was higher with
      CARSI and CARASI indices than that of CURB-65. Positive and negative predictive
      values in predicting death during 6-week follow-up were comparable among 3
      indices examined. The receiver operating characteristic curve values (95%
      confidence interval) for the criteria were 0.67 (0.60-0.75) for CURB-65, 0.64
      (0.60-0.71) for CARSI and 0.64 (0.57-0.71) for CARASI. Comparing receiver
      operating characteristic curves for CURB-65 versus CARSI, or CURB-65 versus
      CARASI, there was no evidence of a difference between the tools, P = 0.35 and
      0.33, respectively. There was good agreement, which was strongly statistically
      significant (kappa = 0.56, P < 0.0001 and kappa = 0.54, P < 0.0001,
      respectively). CONCLUSIONS: Both CARSI and CARASI are useful in predicting deaths
      associated with CAP, including older patients, and may be particularly useful in
      the emergency and community settings.

PMID- 21876428
TI  - Neurological deficits during treatment with tumor necrosis factor-alpha
      antagonists.
AB  - INTRODUCTION: Neurological deficits that occur during treatment with tumor
      necrosis factor (TNF)-alpha antagonists are rare, and their clinical features
      have not been fully elucidated. METHODS: Retrospective review of medical records
      of 9 patients who were given TNF-alpha antagonists, subsequently developed
      neurological deficits and were cared for at the Medical University of South
      Carolina between January 2002 and May 2010. Adverse drug reaction probability
      scale was used for the assessment of their causal connection. RESULTS: The
      underlying diseases for which TNF-alpha antagonists were administered included
      rheumatologic disorders (4), sarcoidosis (3), psoriasis (1) and Crohn's disease
      (1). Etanercept, infliximab or adalimumab was administered to these patients.
      Neurological complications included central or peripheral demyelination (5),
      antiphospholipid syndrome/central nervous system lupus (1), Epstein-Barr virus
      encephalitis (1), axonal sensory polyneuropathy (1) and small fiber
      polyneuropathy (1). TNF-alpha antagonists were discontinued in 8 patients and
      clinical improvement was seen in 3 of them. Additional therapies were given in 4
      patients. An adverse drug reaction probability score suggested probable (3/9) and
      possible (6/9) causal relationships. CONCLUSIONS: Neurological deficits that
      develop during treatment with TNF-alpha antagonists are relatively rare but
      important potential complications of these drugs. Determining if the relationship
      between the neurological deficits and TNF-alpha antagonist therapy is causal can
      be challenging and can impact patient care.

PMID- 21876429
TI  - Persistence of mortality risk in patients with acute cardiac diseases and mild
      thyroid dysfunction.
AB  - INTRODUCTION: There are no studies on the long-term prognostic role of abnormal
      thyrotropin value in patients with acute cardiac diseases. Aim of the study was
      to assess the incidence and persistence of risk of cardiac and overall deaths in
      patients with acute cardiac diseases. METHODS: A total of 1026 patients (mean
      age: 67.7 years) were divided into 4 groups: (1) euthyroid (EU, n=579); (2)
      subclinical-like hypothyroidism (SLHYPO, n=68); (3) subclinical-like
      hyperthyroidism (SLHYPER, n=23) and (4) low-triiodothyronine syndrome (LowT3,
      n=356). Follow-up started from the day of thyroid hormone evaluation (mean follow
      up: 30 months). The events considered were cardiac and overall deaths. RESULTS:
      Survival rate for cardiac death was lower in SLHYPO and in LT3 than in EU (log
      rank test; chi(2)=33.6; P < 0.001). Survival rate for overall death was lower in
      SLHYPO, SLHYPER and LowT3 than in EU (48.3; P < 0.001). After adjustment for
      several risk factors, the hazard ratio for cardiac death was higher in SLHYPO
      (3.65; P=0.004) in LowT3 (1.88; P=0.032) and in SLHYPER (4.73; P=0.047). Hazard
      ratio for overall death was higher in SLHYPO (2.30; P=0.009), in LowT3 (1.63;
      P=0.017) and in SLHYPER than in EU (3.71; P=0.004). Hazards for SLHYPO, SLHYPER
      and LowT3 with respect to EU were proportional over the follow-up period.
      CONCLUSION: In patients with acute cardiac disease, a mildly altered thyroid
      status was associated with increased risk of mortality that remains constant
      during all the follow-up.

PMID- 21876430
TI  - Role of the O-linked beta-N-acetylglucosamine in the cardioprotection induced by
      isoflurane.
AB  - BACKGROUND: Cardiac protection by volatile anesthetic-induced preconditioning and
      ischemic preconditioning have similar signaling pathways. Recently, it was
      reported that augmentation of protein modified with O-linked beta-N
      acetylglucosamine (O-GlcNAc) contributes to cardiac protection. This study
      investigated the role of O-GlcNAc in cardiac protection induced by anesthetic
      induced preconditioning. METHODS: O-GlcNAc-modified proteins were visualized by
      immunoblotting. Tolerance against ischemia or reperfusion was tested in vivo (n =
      8) and in vitro (n = 6). The opening of the mitochondrial permeability transition
      pore (mPTP) upon oxidative stress was examined in myocytes treated with calcein
      AM (n = 5). Coimmunoprecipitation and enzymatic labeling were performed to detect
      the mitochondrial protein responsible for the mPTP opening. RESULTS: Isoflurane
      treatment and the consequent augmentation of O-GlcNAc concentrations reduced the
      infarct size (26 +/- 5% [mean +/- SD], P < 0.001) compared with the control. The
      protective effect of O-GlcNAc was eliminated in the group pretreated with the O
      GlcNAc transferase inhibitor alloxan (39 +/- 5%, P < 0.001). Myocyte survival
      also showed the same result in vitro. Formation of the mPTP was abrogated in the
      isoflurane-treated cells (86 +/- 4%, P < 0.001) compared with the control and
      alloxan-plus-isoflurane-treated cells (57 +/- 7%, P < 0.001).
      Coimmunoprecipitation and enzymatic labeling studies revealed that the O-GlcNAc
      modified, voltage-dependent anion channel restained the mPTP opening.
      CONCLUSIONS: Isoflurane induced O-GlcNAc modification of mitochondrial voltage
      dependent anion channel. This modification inhibited the opening of the mPTP and
      conferred resistance to ischemia-reperfusion stress.

PMID- 21876431
TI  - Incidence of anastomotic leakage after rectal cancer surgery without bowel
      preparation.

PMID- 21876433
TI  - Who is benefited by enteral nutrition via abdominal vagal signaling?

PMID- 21876434
TI  - Should all papillary thyroid microcarcinomas be aggressively treated? An analysis
      of 18,445 cases.
AB  - OBJECTIVE: The purpose of this study was to identify the risk factors that
      predict papillary thyroid microcarcinoma (PTMC)-related death in a large patient
      population to determine which patients need aggressive treatment. BACKGROUND: The
      management of PTMC is controversial and ranges from observation to total
      thyroidectomy. The lack of consensus is predominantly due to the general
      excellent overall prognosis, thereby requiring a large cohort to delineate
      differences in outcome. METHODS: All papillary thyroid cancer patients with tumor
      size of 1 cm or less in the Surveillance, Epidemiology and End Results Cancer
      Database from 1988 to 2007 were identified. Outcomes, including overall and
      disease-specific survival, were compared, and different risk groups were
      evaluated by multivariate analysis. RESULTS: A total of 18,445 cases of PTMC with
      surgery were identified. The 10-year and 15-year overall survivals were 94.6% and
      90.7%, respectively, while disease-specific survivals were 99.5% and 99.3%. Age
      greater than 45 years, male sex, African American or minority race, node
      metastases, extrathyroidal invasion, and distant metastases were stratified to be
      significant risk factors for overall survival. There were 49 thyroid cancer
      related deaths. Forty-five (92%) of the 49 patients had at least 2 risk factors,
      and 51% of these 49 patients had 3 or more risk factors (vs 5.7% in the rest of
      the cohort, P < 0.001). CONCLUSIONS: Although PTMC is generally associated with
      an excellent prognosis, 0.5% patients may die of PTMC. The presence of 2 or more
      risk factors is strongly associated with cancer-related mortality and can help to
      identify patients who should be considered for more aggressive management.

PMID- 21876435
TI  - Weight loss induced by tyrosine kinase inhibitors of the vascular endothelial
      growth factor pathway.
AB  - Weight loss, cachexia and sarcopenia are profound problems in the frail oncologic
      patients. With the development and increasing use of angiogenesis inhibitors in
      metastatic cancer patients, the question arises as to their influence on body
      weight and composition. Angiogenesis is not only important for the growth,
      development and metastatic potential of tumors but also for physiological
      processes in adipogenesis. A less known approach of angiogenesis inhibitors is
      their experimental use in obese models. This review focuses on the effects on the
      body weight and composition of angiogenesis inhibitors, especially of those
      targeting the vascular endothelial growth factor pathway.

PMID- 21876436
TI  - Methylnaltrexone in treatment of opioid-induced constipation in a pediatric
      patient.
AB  - OBJECTIVES: Opioid-induced constipation persists as a challenge in the management
      of chronic pain treated with opioid therapy. Multiple opioid antagonists have
      been applied in attempt to combat the gastrointestinal side effects of opioid
      analgesia, however their lipid-soluble nature allows passage into the central
      nervous system and consequent antagonism of centrally mediated analgesia. In
      contrast, methylnaltrexone offers the advantage of peripheral receptor-specific
      opioid antagonism due to chemical alterations conferring greater polarity and
      less lipid solubility. We present use of enteral methylnatrexone to treat severe
      opioid-induced constipation in a young boy who had failed treatment with the non
      specific opioid antagonist, naloxone. This case reports describes the safe
      transition from enteral naloxone to enteral methylnaltrexone and discusses the
      potential risk of relative opioid toxicity during the transition. METHODS: Though
      methylnaltrexone has approved for subcutaneous use, the characteristics of the
      patient s disease required enteral administration which had not been described in
      pediatric dosing. Based on conservative extrapolation of data from adult dosing,
      a methylnaltrexone dosing regimen was selected and the naloxone was weaned over
      two days in an effort to avoid a relative opioid overdose. RESULTS: The patient
      was successfully transitioned to methylnaltrexone from naloxone over two days. He
      did experience increased sedation during this time however no severe respiratory
      depression occurred due to the cessation of chronic central opioid antagonism
      causing a relative opioid toxicity. Following the institution of
      methylnaltrexone, his opioid requirement significantly decreased and his
      gastrointestinal symptoms improved. DISCUSSION: Our case report demonstrates safe
      transition from enteral naloxone to enteral methylnaltrexone in a pediatric
      patient, avoiding the serious consequences of relative opioid toxicity. This
      patient experienced significant improvement of opioid-induced constipation and
      reduction in opioid requirements and it is possible that other patients would
      benefit as well. The role of enteral methylnaltrexone deserves further
      investigation.

PMID- 21876437
TI  - Antitumor promoting potential of selected phytochemicals derived from spices:  a
      review.
AB  - Carcinogenesis is a multistep process exhibiting deregulation in multiple
      cellular signaling pathways. Therefore, specific agent based treatments that
      target only one pathway usually fail in cancer therapy. The combination
      treatments using chemotherapeutic agents with distinct molecular mechanisms are
      considered more promising for higher efficacy; however, using multiple agents
      contributes to added toxicity. However, the in-vitro and in-vivo studies in the
      last few decades have demonstrated that some phytochemicals derived from 'natural
      products' such as fruits, vegetables and certain spices, referred to as
      chemopreventive agents, including capsaicin, trans-anethole, thymoquinone,
      diosgenin, allicin, can not only reduce the risk of acquiring specific cancer but
      also have been shown to suppress cancer cell proliferation, inhibit growth factor
      signaling pathways, induce apoptosis, inhibit nuclear factor-kappaB, AP-1, Akt,
      MAPK, Wnt, Notch, p53, AR, ER, and JAK-STAT, etc., activation pathways, inhibit
      angiogenesis, suppress the expression of antiapoptotic proteins, and inhibit
      cyclooxygenase-2. This study describes the above active components of some of the
      major spices, their mechanisms of action and their potential in prevention of
      various cancers.

PMID- 21876438
TI  - Assessing tear film on soft contact lenses with lateral shearing interferometry.
AB  - OBJECTIVES: Evaluating precorneal tear film is one of important clinical
      measurements for assessing health of anterior eye. Contact lens wear is known to
      influence the quality of tear film. The aim was to evaluate the applicability of
      lateral shearing interferometry technique in the noninvasive assessment of the
      effects of contact lens replacement modality and its water content on tear film
      stability. METHODS: Sixteen regular soft contact lens wearers took place in the
      study. Lateral shearing interferometry measurements, in suppressed blinking
      conditions, were taken in the mornings and afternoons, after a minimum of 5 hours
      of lens wear for the daily lenses, and after 2 weeks and 1 month for the
      fortnightly and monthly lens replacement modalities, respectively. RESULTS:
      Significant differences (paired bootstrap-based Behrens-Fisher test, P < 0.05) in
      the tear film surface quality were found between all considered pairs of
      replacement modalities except for the daily and fortnightly lenses measured in
      the afternoon of the first day of wear. Significant worsening (paired bootstrap
      based Behrens-Fisher test, P < 0.001) of tear film quality was found for the low
      water content materials. CONCLUSIONS: Lateral shearing interferometry is a
      powerful method for the noninvasive assessment of tear film surface quality on
      soft contact lenses that may find, in future, its use in the clinical assessment
      of anterior eye's health.

PMID- 21876439
TI  - Trichosporon asahii keratitis in a patient with a type I Boston keratoprosthesis
      and contact lens.
AB  - PURPOSE: The aim of the study was to report a case of Trichosporon asahii in a
      patient with a type I Boston keratoprosthesis and contact lens with review of the
      literature. METHODS: A case report and literature review are provided. RESULTS: A
      70-year-old monocular South Asian man with light perception vision and dense
      corneal scarring from previously failed amniotic membrane grafting and one failed
      corneal transplant was evaluated for a keratoprosthesis for visual
      rehabilitation. Three months after undergoing uneventful implantation of a type I
      Boston keratoprosthesis and placement of a therapeutic contact lens, he was found
      on routine follow-up to have a corneal infiltrate that was culture positive for
      T. asahii. The fungal keratitis was successfully treated with topical
      amphotericin B and oral ketoconazole. CONCLUSIONS: Contact lens wear is a known
      risk factor for fungal keratitis. Trichosporon is an uncommon agent of fungal
      keratitis. We report the first known case of fungal keratitis caused by T.asahii
      in a patient with a keratoprosthesis and contact lens.

PMID- 21876440
TI  - Do continued antidepressants protect against dementia in patients with severe
      depressive disorder?
AB  - Studies on humans show that depressive disorder is associated with an increased
      risk of developing cognitive dysfunction, and animal studies suggest that
      antidepressants may have neuroprotective abilities. On the basis of these
      observations, it was hypothesized that treatment with antidepressants may
      decrease the risk of developing dementia in patients with depression. We
      investigated whether continued treatment with antidepressants is associated with
      a decreased rate of dementia in a population of patients discharged from
      psychiatric healthcare service with a diagnosis of depression. We used register
      data on all prescribed antidepressants in all patients discharged from
      psychiatric healthcare service with a diagnosis of depression and with subsequent
      diagnoses of dementia in Denmark from 1995 to 2005. A total of 37 658 patients
      with a diagnosis of depression at their first psychiatric contact and who were
      exposed to antidepressants after discharge were included in the study. A total of
      2007 patients (5.3%) were subsequently diagnosed with dementia of any kind. The
      rate of dementia decreased during periods of two or more prescriptions of older
      antidepressants compared with the period of only one prescription of older
      antidepressants [relative risk (RR)=0.83 (95% confidence interval (CI)=0.70
      0.98)]. This finding was replicated with Alzheimer's disease as the outcome
      [RR=0.66 (95% CI=0.47-0.94)] but not with dementia of other kinds as the outcome
      [RR=0.88 (95% CI=0.73-1.06)]. In contrast, during periods of continued use of
      selective serotonin reuptake inhibitors or newer nonselective serotonin reuptake
      inhibitors, the rate of dementia was not decreased, regardless of the subtype of
      dementia. It was concluded that continued long-term treatment with older
      antidepressants is associated with a reduced rate of dementia in patients treated
      in psychiatric healthcare settings, whereas continued treatment with other kinds
      of antidepressants is not. Methodological reasons for these findings cannot be
      excluded because of the nonrandomized nature of data.

PMID- 21876441
TI  - Predictors of excellent response to lithium:  results from a nationwide register
      based study.
AB  - The aim of this study was to identify sociodemographic and clinical predictors of
      excellent response, that is, 'cure' of future affective episodes, to lithium in
      monotherapy. We used nationwide registers to identify all patients with a
      diagnosis of bipolar disorder in psychiatric hospital settings who were
      prescribed lithium from 1995 to 2006 in Denmark (N=3762). Excellent lithium
      responders were defined as patients who after a stabilization lithium start-up
      period of 6 months, continued lithium in monotherapy without getting
      hospitalized. The rate of excellent response to lithium in monotherapy was 8.9%
      [95% confidence interval (CI): 7.9-9.9] at 5-year follow-up and 5.4% (95% CI: 4.4
      6.3) at 10-year follow-up. The rate of nonresponse to lithium monotherapy was
      significantly increased for female patients [hazards ratio (HR)=1.12, 95% CI:
      1.04-1.21) and for patients with a depressive index episode compared with
      patients in remission or with a diagnosis of other or unspecified bipolar
      disorder before first lithium purchase (HR=1.13, 95% CI: 1.03-1.25). The rate of
      nonresponse increased by 3% (95% CI: 2-5%) for every psychiatric hospitalization
      before first purchase of lithium. Patients with somatic comorbidity had increased
      rates of non-response to lithium compared with patients without somatic
      comorbidity (HR=1.23, 95% CI: 1.00-1.52).It is concluded that the prevalence of
      excellent response to lithium monotherapy is low and such patients are
      characterized by few earlier psychiatric hospitalizations, a manic index episode
      before lithium and reduced somatic comorbidity.

PMID- 21876442
TI  - The METEOR study:  frequency of metabolic disorders in patients with
      schizophrenia. Focus on first and second generation and level of risk of
      antipsychotic drugs.
AB  - The objective of this crosssectional study was to estimate the prevalence of
      metabolic disorders and hypertension in patients with schizophrenia and to
      compare prevalence between patients treated with first-generation (FGA) and
      second-generation (SGA) antipsychotic drugs. The study included 2270 adults with
      schizophrenia. Patients were assigned to an FGA or SGA stratum on the basis of
      current treatment. Data were collected on sociodemographic, lifestyle and
      clinical variables. Blood pressure, waist and hip circumference, blood glucose,
      triglycerides and cholesterol were measured. The primary evaluation criterion was
      the prevalence of a glycaemic disorder. Secondary criteria were the prevalence of
      dyslipidaemia, obesity, hypertension and metabolic syndrome. A propensity score
      was used to control imbalance between strata. The prevalence of glycaemic
      disorders was 31.1% (FGA) and 27.6% (SGA). No between-strata difference in
      prevalence was observed for glycaemic disorders, dyslipidaemia or metabolic
      syndrome. The prevalence of hypertension was higher (P=0.033) in the FGA group.
      The proportion of women (but not men) who were overweight or obese was higher in
      the SGA group (P=0.035), as was the proportion reporting weight gain of more than
      5 kg (P<0.001). In an exploratory unadjusted post-hoc analysis, significantly
      higher frequencies of dysglycaemia (28.5 vs. 22.0%; P=0.006), low HDL cholesterol
      (35.3 vs. 29.7%; P=0.023) and metabolic syndrome (36.7 vs. 30.7%; P=0.021) were
      observed in patients taking SGAs considered to carry high metabolic risk compared
      with those taking low-risk agents. In conclusion, metabolic disorders are
      prevalent in patients with schizophrenia treated with antipsychotics and are
      under-diagnosed and under-treated.

PMID- 21876443
TI  - Influence of the combination of low-density lipoprotein receptor and interleukin
      28B genotypes on lipid plasma levels in HIV/hepatitis C-coinfected patients.

PMID- 21876445
TI  - HIV-1 reverse transcriptase nucleotide substitutions in subtype C-infected, drug
      naive, and treatment-experienced patients in South India.

PMID- 21876444
TI  - Pharmacokinetics of lopinavir/ritonavir crushed versus whole tablets in children.
AB  - OBJECTIVE: Lopinavir/ritonavir (Kaletra) is first-line therapy for pediatric HIV
      infection. In clinical practice, Kaletra tablets are occasionally crushed for
      pediatric administration. This study compared lopinavir/ritonavir exposure
      between whole and crushed tablets in HIV-infected children. DESIGN: This was a
      randomized, open-label, cross-over study of pediatric patients taking
      lopinavir/ritonavir as part of their antiretroviral regimen. Each subject had 2
      separate (within 30 days) steady-state 12-hour pharmacokinetic (PK) studies with
      crushed and whole 200/50 mg lopinavir/ritonavir tablets. METHODS: PK blood
      samples were drawn at 0 (predose), 1, 2, 4, 6, 8, and 12 hours postdose.
      Lopinavir and ritonavir plasma concentrations measured by high-performance liquid
      chromatography were used to calculate non-compartmental area under the
      concentration versus time curve (AUC) and clearance. Wilcoxon signed-rank tests
      compared PK values between crushed and whole tablets. RESULTS: Twelve children,
      median age of 13 years (10-16 years), took 550/138 mg.m(-2) per day
      lopinavir/ritonavir divided every 12 hours. The median lopinavir AUC after
      crushed and whole tablets were 92 mg.hr.L(-1) and 144 mg.hr.L(-1), respectively,
      with an AUC ratio of 0.55 (P = 0.003). Median ritonavir AUC of crushed and whole
      tablets were 7 mg.hr.L(-1) and 13.3 mg.hr.L(-1), respectively, with an AUC ratio
      of 0.53 (P = 0.006). CONCLUSIONS: Administration of crushed 200/50 mg
      lopinavir/ritonavir tablets to children significantly reduced lopinavir and
      ritonavir exposure with a decrease in AUC by 45% and 47%, respectively. The
      administration of crushed tablets would require higher doses and therapeutic drug
      monitoring to ensure adequate lopinavir exposure in patients requiring this
      practice. The use of crushed lopinavir/ritonavir tablets should be avoided, if
      possible.

PMID- 21876446
TI  - Randomized trial comparing dose reduction and growth factor supplementation for
      management of hematological side effects in HIV/hepatitis C virus patients
      receiving pegylated-interferon and ribavirin.
AB  - BACKGROUND: Pegylated-interferon (PEG-IFN) and ribavirin (RBV), current standard
      treatment for hepatitis C virus (HCV) infection, are frequently associated with
      neutropenia and anemia, leading to high treatment discontinuation rates in
      HIV/HCV-coinfected patients. Our objective was to compare the effectiveness of
      intervening with hematologic growth factors versus dose reductions of standard
      HCV therapy for the management of treatment-induced hematologic disorders.
      METHODS: Ninety-two HIV/HCV-coinfected, therapy-naive subjects received PEG-IFN
      alfa-2b 1.5 MUg.kg-1.wk-1 and RBV 13 +/- 2 mg.kg-1.d-1 for up to 48 weeks. Before
      treatment initiation, subjects were randomized to subsequently receive growth
      factors, recombinant human erythropoietin (rHuEPO) and/or granulocyte colony
      stimulating factor, or dose reduction (RBV and/or PEG-IFN) for anemia and
      neutropenia management, respectively. We analyzed the ability of each management
      strategy to control anemia and neutropenia and the percentage of subjects who
      achieved a successful treatment outcome according to the different management
      strategies. RESULTS: During treatment, 43 subjects developed anemia (human
      erythropoietin, n = 24; dose reduction, n = 19), whereas 25 subjects developed
      neutropenia (granulocyte colony-stimulating factor, n = 10; dose reduction, n =
      15). After the intervention, the increase in both hemoglobin and absolute
      neutrophil counts did not differ between the 2 side effect management strategies.
      Sustained response percentages were similar comparing anemic and neutropenic
      subjects regardless of management strategy (anemia: recombinant human
      erythropoietin, 29% versus dose reduction, 21%, P = 0.92; neutropenia:
      granulocyte colony-stimulating factor, 40% versus dose reduction, 20%, P = 0.46).
      CONCLUSIONS: Growth factor supplementation and dose reduction do not seem to
      differ as management strategies for anemia and neutropenia in HIV/HCV-coinfected
      individuals treated with PEG-IFN/RBV.

PMID- 21876447
TI  - Changing predictors of mortality over time from cART start: implications for
      care.
AB  - OBJECTIVE: To determine predictors of mortality and changes in those predictors
      over time on combination antiretroviral therapy (cART) in South Africa. DESIGN: A
      cohort study. METHODS: Using routine clinic data with up to 4 years follow-up
      after antiretroviral therapy initiation and with death ascertainment from a
      national vital statistics register, we used proportional hazards modeling to
      assess baseline and time-updated predictors of mortality and changes in strength
      of those predictors over time on cART. Furthermore, we compared CD4 count among
      individuals who died by duration on cART. RESULTS: Fifteen thousand sixty
      subjects (64% men, median CD4 count 127 cells/mm3) started antiretroviral therapy
      between January 2003 and January 2008. Over a median follow-up of 1.8 years, 2658
      subjects died. The baseline characteristics of WHO stage, hemoglobin, CD4 count,
      HIV RNA level, and symptoms were all associated with mortality during the first
      12 months of cART but lost association thereafter. However, time-updated factors
      of CD4 count, body mass index, symptoms, anemia, and HIV RNA suppression remained
      strong predictors of death. Most recent CD4 count before death rose from 71
      during the first 3 months of cART to 175 cells per cubic millimeter after >3
      years of cART. CONCLUSION: Over 4 years of cART, risk of death declined and
      associations with mortality changed. An increase in CD4 count at death and
      changing associations with mortality may suggest a shift in causes of death,
      possibly from opportunistic infections to other infections and chronic illnesses.

PMID- 21876448
TI  - Longitudinal assessment of interleukin 7 plasma levels in HIV-infected patients
      in the absence of and under antiretroviral therapy.
AB  - BACKGROUND: Cross-sectional studies in HIV-positive patients have suggested that
      interleukin 7 (IL-7) may increase in parallel to CD4 decline during the natural
      course of HIV infection. We tested this hypothesis in a longitudinal study
      examining the evolution of IL-7 and CD4 counts in 2 different scenarios. METHODS:
      IL-7 and CD4 counts were regularly monitored in 30 drug-naive patients during a
      follow-up period of 46 +/- 14 months in the absence of therapy and in 42 patients
      who started highly active antiretroviral therapy and maintained undetectable
      viremia for 2 years. Multivariate linear regression analysis was used to
      ascertain what factors were associated with IL-7 variations during follow-up.
      RESULTS: In antiretroviral therapy-naive patients, CD4 counts significantly
      decreased (P < 0.0001), whereas plasma HIV-RNA and IL-7 levels remained fairly
      stable. In patients on highly active antiretroviral therapy, CD4 counts
      significantly increased (P < 0.0001) and IL-7 tended to decrease (P = 0.1). There
      was no correlation between CD4 and IL-7 variations either in the naive or in the
      treated population. The only parameter significantly associated with IL-7
      variation during follow-up was its baseline level that showed a negative
      correlation. CONCLUSIONS: In HIV patients with low or moderate degree of
      immunodeficiency, CD4 counts and plasma IL-7 levels do not evolve in parallel,
      suggesting that other factors different from CD4 counts must be involved in the
      upregulation of IL-7 observed in HIV infection.

PMID- 21876449
TI  - Increased acceptance rates of HIV screening using opt-out consent methods in an
      urban emergency department.
AB  - BACKGROUND: Optimal methods for implementing HIV screening in health care
      settings remain unknown. OBJECTIVE: To compare the acceptance rates of emergency
      department HIV screening when supplemental staff use opt-in and opt-out consent
      methods. METHODS: Experimental equivalent time-sample, conducted in an urban
      emergency department with an annual census of 80,000 visits. HIV screeners
      performed nontargeted HIV screening using point-of-care, rapid HIV tests.
      Eligible patients were medically stable, English or Spanish speaking, >=13 or
      <=64 years, not HIV tested in past 6 months, and not psychiatrically impaired.
      Screeners offered eligible patients HIV screening using either opt-in or opt-out
      consent methods on alternate weeks. Main outcome measures were the acceptance
      rate of HIV screening and the association between opt-out rapid HIV screening and
      acceptance. RESULTS: Of the eligible patients, 2409 were offered HIV screening,
      with 1209 (50%) on opt-in days and 1200 (50%) on opt-out days. The mean age was
      40 years, 52% were male, 45% were Black, 28% Hispanic, and 15% white. The
      acceptance rate of opt-in HIV screening was 63% [767 of 1209, 95% confidence
      interval (CI): 61% to 66%] and the acceptance rate of opt-out HIV screening was
      78% (931 of 1200, 95% CI: 75% to 80%), absolute difference 14% (95% CI: 11% to
      18%). The acceptance rate of opt-out HIV screening remained greater after
      adjusting for patient demographics, admission status, acuity, treatment area,
      privacy of encounter, and screening staff identity (adjusted odds ratio: 2.0, 95%
      CI: 1.7 to 2.4). CONCLUSIONS: Opt-out HIV screening using supplemental staff
      increases patient acceptance and should be considered as the consent methodology
      of choice.

PMID- 21876450
TI  - Efficiencies in AIDS programming:  the rhetoric and the realities.

PMID- 21876451
TI  - Intraoperative airway obstruction due to dissection of a reinforced endotracheal
      tube in a prone patient.

PMID- 21876453
TI  - Use of tranexamic acid as a rescue measure to achieve hemostasis after massive
      blood loss in a pediatric neurosurgical patient.

PMID- 21876455
TI  - Atlantoaxial rotatory subluxation after surgical relocation of Sprengel
      deformity:  a case report.
AB  - We report a case of atlantoaxial rotatory subluxation developed after scapular
      relocation for Sprengel deformity in a 5-year-old girl. Scapular relocation
      descended the scapula by 60%, and achieved a normal shoulder joint motion.
      However, atlantoaxial rotatory subluxation developed, probably by pulling force
      of the tightened anterior fibers of upper trapezius muscle. Atlantoaxial joint
      was reduced easily under general anesthesia and muscle relaxant, along with
      surgical release of the tight band at the anterior part of trapezius muscle,
      which was maintained by halovest immobilization.

PMID- 21876456
TI  - Immunotherapy for non-small cell lung cancer: novel approaches to improve patient
      outcome.
AB  - INTRODUCTION: Non-small cell lung cancer (NSCLC) is often diagnosed in advanced
      stages and is associated with poor outcomes. Existing standards of care for NSCLC
      result in low overall cure rates, suggesting that novel treatment approaches are
      needed. In this review, we provide an updated look at the clinical data on
      immunotherapeutic interventions, which potentiate the immune system's response to
      lung tumor cells. METHODS: We searched articles on PubMed and abstracts from
      recent oncology meetings for publications on immunotherapies with clinical
      applicability to the treatment of NSCLC. RESULTS: Results from phase 2 trials
      show vaccine therapies, which target either tumor cells themselves or aberrantly
      expressed tumor markers (mucin 1, melanoma-associated antigen 3, or epidermal
      growth factor), may be promising immunotherapeutics for NSCLC. Antigen
      independent immunotherapies, such as anti-cytotoxic T-lymphocyte antigen-4
      monoclonal antibodies, talactoferrin alfa, and toll-like receptor 9 agonists, act
      on a stimulated immune system regardless of the tumor antigen and may be feasible
      interventions for metastatic NSCLC. Several immunotherapies are undergoing phase
      3 studies to assess optimal treatment settings and to determine clinical benefit
      compared with current standard treatments for NSCLC. CONCLUSIONS: A growing body
      of evidence suggests that immune responses to lung tumors are present.
      Immunotherapeutic interventions, including vaccine therapy and antigen
      independent immunomodulatory strategies, may improve outcomes in NSCLC.
      Furthermore, treatments that enhance antitumor immune responses may prove to be
      synergistic with chemotherapy. Identification of biomarkers and further
      elucidation of immunotherapeutic mechanisms of action will be essential in
      determining which patients will experience the greatest benefit from
      immunotherapy.

PMID- 21876457
TI  - Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine
      followed by adjuvant chemotherapy in patients with malignant pleural
      mesothelioma.
AB  - INTRODUCTION: Malignant pleural mesothelioma is a fatal neoplasm related to
      asbestos exposure. We investigated the effects of pleurectomy/decortication
      (P/D), hyperthermic pleural lavage with povidone-iodine and adjuvant chemotherapy
      in patients with malignant pleural mesothelioma. PATIENTS AND METHODS:
      Observational prospective study of patients referred for multimodality therapy
      and operated on at our institution between October 2004 and May 2010. Thirty-six
      selected patients underwent P/D and hyperthermic pleural lavage, prophylactic
      radiotherapy, and adjuvant chemotherapy. All patients were reviewed at 4 weeks
      and then 6 monthly in the outpatient clinic, with positron-emission tomography
      computed tomography. Second-line treatments were administered when appropriate.
      RESULTS: Thirty-day mortality was nil. Nine patients experienced postoperative
      complications: persistent air leak (n = 5, 13.9%), chylothorax requiring surgical
      intervention (n = 4, 11%), and adult respiratory distress syndrome (n = 1, 3.9%).
      Fourteen of 36 patients were alive at last follow-up (median follow-up: 33
      months, range: 12-63 months). Ten patients were alive with no evidence of disease
      recurrence, four patients were alive with disease recurrence, and 22 patients had
      died of disease progression. Overall median survival (Kaplan-Meier) was 24 months
      (95% confidence interval: 18.5-29.4 months). One-year survival was 91.7%, and 2
      year survival was 61%. Patients undergoing complete macroscopical resection (R0
      R1) had a significantly better survival than those undergoing an incomplete
      macroscopical resection (R2) (median overall survival: 32 months versus 18.9
      months, p = 0.012). CONCLUSION: In our experience, P/D combined with hyperthermic
      pleural lavage with povidone-iodine and adjuvant chemotherapy is a well-tolerated
      multimodality treatment associated with low morbidity and mortality. This
      multimodality treatment compares favorably with classical trimodality regimens
      involving chemotherapy, extrapleural pneumonectomy, and adjuvant radiotherapy, in
      our experience. Study limitations include small sample size, nonrandomization,
      and patient selection bias.

PMID- 21876458
TI  - The role of the 18f-fluorodeoxyglucose-positron emission tomography scan in the
      Nederlands Leuvens Longkanker screenings Onderzoek lung cancer screening trial.
AB  - BACKGROUND: In computed tomography lung cancer screening programs, up to 30% of
      all resections are futile. OBJECTIVE: To investigate whether a preoperative
      positron emission tomography (PET) after a conclusive or inconclusive nonsurgical
      workup will reduce the resection rate for benign disease in test-positive
      participants of a lung cancer screening program. METHODS: 18F-Fluorodeoxyglucose
      PET scans were made in 220 test positives. Nodules were classified as positive,
      indeterminate, or negative based on visual comparison with background activity.
      Gold standard for a positive PET was the presence of cancer in the resection
      specimen or the detection of cancer during more than 2 years follow-up.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value (NPV) were calculated at participant level and 95% confidence intervals
      (CIs) constructed. RESULTS: The sensitivity of PET to detect cancer was 84.2%
      (95% CI: 77.6-90.7%), the specificity 75.2% (95% CI: 67.1-83.3), the positive
      predictive value 78.9% (95% CI: 71.8-86.0), and the NPV 81.2% (95% CI: 73.6
      88.8). The resection rate for benign disease was 23%, but 26% of them had a
      diagnosis with clinical consequences. A preoperative PET after an inconclusive
      nonsurgical workup reduced the resection rate for benign lesions by 11 to 15%, at
      the expense of missing 12 to 18% lung cancer cases. A preoperative PET after a
      conclusive nonsurgical workup reduced the resection rate by 78% at the expense of
      missing 3% lung cancer cases. CONCLUSION: A preoperative PET scan in participants
      with an inconclusive nonsurgical workup is not recommended because of the very
      low NPV, but after a conclusive nonsurgical workup, the resection rate for benign
      disease can be decreased by 72%.

PMID- 21876459
TI  - Immunohistochemical expression of VEGF, HIF1-a, and PlGF in malignant melanomas
      and dysplastic nevi.
AB  - We evaluated the role of vascular endothelial growth factor (VEGF), placental
      growth factor (PlGF), and hypoxia-inducible factor 1-a (HIF1-a) in melanoma
      angiogenesis and investigated their expression in dysplastic nevi, as potential
      melanoma precursors. In addition, we examined a possible correlation of VEGF
      expression with PlGF and HIF1-a. These factors were detected
      immunohistochemically in 95 melanomas of all types and stages and in 28
      dysplastic nevi. We used 10 intradermal melanocytic nevi as controls. HIF1-a was
      expressed in 93 out of 95 (97.89%) melanomas and in none of the dysplastic or
      control nevi. HIF1-a expression was more intense in melanocytes around necrotic
      areas but did not correlate with melanoma type, the Clark staging or the Breslow
      thickness. A strong positive association was detected between HIF1-a and VEGF
      expression in all cases. VEGF was detected in 82 out of 95 (86.31%) melanomas and
      in 21 out of 28 (75%) dysplastic nevi, whereas it was expressed weakly in
      neoplastic cells of the controls. Its expression was more intense in melanomas,
      especially in nodular melanomas of elevated stage and thickness. PIGF was
      detected in 46 out of 95 (48.42%) melanomas and in none of the nevi. Expression
      did not correlate with melanoma staging nor thickness; however, it was more
      intense in superficial spreading melanomas, where a weak positive association
      between VEGF and PlGF was also detected. There was no association between HIF1-a
      and PlGF in any melanoma type. Hypoxia, through the expression of HIF1-a, plays a
      key role in melanoma progression; it activates VEGF secretion, which induces
      angiogenesis and metastasis. The role of PlGF seems to be limited.

PMID- 21876460
TI  - Prognostic significance of phosphorylated signal transducer and activator of
      transcription 3 and suppressor of cytokine signaling 3 expression in human
      cutaneous melanoma.
AB  - Cutaneous malignant melanoma is one of the most common and aggressive forms of
      human cancers and has a poor prognosis. Activation of signal transducer and
      activator of transcription 3 (STAT3) has been found in several human cancers and
      is thought to correlate aggressive disease and poor response. In this study, we
      investigated the clinical role of STAT3 and its natural inhibitor, suppressor of
      cytokine signaling 3 (SOCS3), in human cutaneous melanoma development and
      progression. Immunohistochemical analysis of pSTAT3, SOCS3, matrix
      metalloproteinase (MMP)-2, and MMP-9 expression was performed on 90 primary
      melanomas and 43 common melanocytic nevi specimens. The expression of STAT3 mRNA
      was further detected by in-situ hybridization in the same cohort of patients. The
      association of STAT3 mRNA, pSTAT3, and SOCS3 protein expression with
      clinicopathological parameters and patient survival was analyzed. Altered
      expression of STAT3 mRNA, pSTAT3, and SOCS3 protein was observed in melanoma
      specimens, compared with benign melanocytic nevi. High expression of pSTAT3 was
      correlated to large tumor diameter, depth of tumor invasion, tumor lymph node
      metastasis, MMP-2 and MMP-9 expression, and poor patient survival. Decreased
      expression of SOCS3 was correlated to depth of tumor invasion, tumor lymph node
      metastasis, the expression of MMP-2, MMP-9, and pSTAT3, and poor patient
      survival. Moreover, the expression of pSTAT3 was conversely correlated to SOCS3
      expression in melanoma. Our results indicate that deregulated expression of
      pSTAT3 and SOCS3 might possess potential roles in the development and progression
      of human cutaneous melanoma.

PMID- 21876461
TI  - Transcranial focused ultrasound to the thalamus alters anesthesia time in rats.
AB  - A pulsed application of focused ultrasound (FUS) to the regional brain tissue
      alters the state of tissue excitability and thus provides the means for
      noninvasive functional neuromodulation. We report that the application of
      transcranial FUS to the thalamus of anesthetized rats reduced the time to
      emergence of voluntary movement from intraperitoneal ketamine/xylazine
      anesthesia. Low-intensity FUS was applied to the thalamus of anesthetized
      animals. The times required for the animals to show distinct
      physiological/behavioral changes were measured and compared with those times
      required in a control session without sonication. The sonication significantly
      reduced the time to show pinch response and voluntary movement. The modulatory
      effects of FUS on anesthesia suggest potential therapeutic applications for
      disorders of consciousness such as minimally consciousness states.

PMID- 21876462
TI  - Response inhibition or salience detection in the right ventrolateral prefrontal
      cortex?
AB  - This study addresses the question of whether frontal activation in response
      inhibition tasks is specifically associated with the suppression of a motor
      response. An alternative model suggests a role in the detection of behaviorally
      relevant or salient events. For this purpose, we used functional MRI with an
      auditory go/no-go paradigm. This paradigm allowed the disentangling of inhibition
      related from salience-related effects, which were associated with different
      frontal regions. Importantly, the right ventrolateral prefrontal cortex
      consistently showed sensitivity for salience but not for inhibition requirements.
      This reflects a more general salience-detection mechanism, which is not specific
      for response-inhibition tasks.

PMID- 21876463
TI  - Intersectin 1 contributes to phenotypes in vivo: implications for Down's
      syndrome.
AB  - Intersectin 1 (ITSN1) is a human chromosome 21 (HSA21) gene product encoding a
      multidomain scaffold protein that functions in endocytosis, signal transduction,
      and is implicated in Down's syndrome, Alzheimer's Disease, and potentially other
      neurodegenerative diseases through activation of c-Jun N-terminal kinase. We
      report for the first time that ITSN1 proteins are elevated in individuals with
      Down's syndrome of varying ages. However, ITSN1 levels decreased in aged cases
      with Down's syndrome with Alzheimer's disease-like neuropathology. Analysis of a
      novel ITSN1 transgenic mouse reveals that ITSN1 overexpression results in a sex
      dependent decrease in locomotor activity. This study reveals a link between
      overexpression of specific ITSN1 isoforms and behavioral phenotypes and has
      implications for human neurodegenerative diseases such as Down's syndrome and
      Alzheimer's disease.

PMID- 21876464
TI  - P-chlorophenylalanine increases glutamate receptor 1 transcription in rat
      amygdala.
AB  - The amygdala is a key limbic structure strongly implicated in both epilepsy and
      anxiety disorders. Epilepsy-like mechanisms involve an increased glutamatergic
      activity, whereas disturbances in serotonin [5-hydroxytryptamine (5-HT)] systems
      are associated with anxiety-like behavior. Previous studies suggest that low 5-HT
      increases amygdala excitability, but the molecular mechanisms are not well
      characterized. Herein we explore the ability of low serotonin to increase
      glutamate receptor transcription. Using quantitative reverse transcriptase
      polymerase chain reaction, we found that rats treated with P-chlorophenylalanine,
      an inhibitor of tyrosine-5-hydroxylase, resulted in a 21-fold increase in
      glutamate receptor 1 (GluR1) mRNA expression in the amygdala. These results
      suggest that low 5-HT induces hyperexcitability of amygdala neurons by increasing
      GluR1 transcription, and the upregulation of amygdala GluR1 may be important in
      the pathophysiology of anxiety disorders.

PMID- 21876465
TI  - Choice-option evaluation is preserved in early Huntington and Parkinson's
      disease.
AB  - The ability to choose effectively when faced with potential risks and rewards is
      fundamental for adaptive survival. The striatum has a well-established role
      supporting learning from the outcomes of decisions, but it remains unclear
      whether this structure is also necessary for computing expected value (i.e.,
      advantageousness of potential decisions) when all information is explicitly
      given. We addressed this question presenting simple monetary gambles, where all
      decisional parameters were given and outcome feedback was absent, to patients
      with early Huntington's and Parkinson's disease, taken as complementary models of
      striatal dysfunction. Behavioural responses and associated times were found to be
      unaltered. This negative finding suggests that striatal activity may not be
      essential for decision-making in situations where all information is provided and
      learning from outcomes is unnecessary.

PMID- 21876466
TI  - Effect of intensity accents on the detection of interonset interval variations.
AB  - Intensity effect on interonset interval (IOI) timing perception was investigated
      in an event-related potential experiment by manipulating the onset and intensity
      of one tone in an isochronous sequence. The results revealed that lengthened IOI
      elicited a larger P3 than the shortened or standard IOI, suggesting that more
      attention should be focused because of an additional stimulation of temporally
      driven expectancy induced by an onset delay. Furthermore, P3 latency for IOI
      occurred later when preceding softer tones than when preceding louder or standard
      tones, implicating that softer tone might introduce a disturbance and impede the
      entrainment of high-level processing in the temporal perception. Importantly,
      louder accents reduced the sensitivity of shortened and standard IOIs, supporting
      the prediction of compensation hypothesis.

PMID- 21876467
TI  - Effective inhibition of irradiation on human gliomas growth in vitro and in vivo
      after epidermal growth factor receptor silencing with RNA interference.
AB  - In this study, we found that irradiation in the presence of small interfering RNA
      epidermal growth factor receptor (EGFR) arrested U373 glioma cells in G0 and G1
      phases, delayed cell cycle progression, and effectively inhibited cell
      proliferation compared with cells that received only radiotherapy. In addition,
      combined therapy enhanced the percent of apoptotic U373 cells in vitro and also
      reduced the tumor size and increased the survival rate in tumor xenograft
      studies. This study demonstrates the antitumor activity of ionizing radiation
      therapy in combination with small interfering RNA-EGFR in gliomas both in vitro
      and in vivo and provides a scientific rationale for targeting EGFR to enhance the
      sensitivity to radiotherapy in patients with glioblastoma multiforme.

PMID- 21876468
TI  - The Poggendorff illusion effect influenced by top-down control: evidence from an
      event-related brain potential study.
AB  - Event-related brain potentials were used to examine the neural correlates of the
      visual illusion effect in the Poggendorff illusion. In this study, there were
      three tasks, namely, illusion task 1, illusion task 2 (similar to the classical
      Poggendorff figures, where the two oblique lines in which individuals were prone
      to judge to be collinear, were not collinear in fact), and baseline task. Scalp
      event-related brain potential analysis revealed that (a) both illusion task 1 and
      illusion task 2 elicited a more negative event-related brain potential deflection
      (N400-600) than did baseline task, approximately 400 ms after onset of the
      stimuli, and (b) high-level cognitive control system is, through enhancing the
      influence of the context on identifying the relationships of the two oblique
      lines, involved in generating the Poggendorff illusion.

PMID- 21876469
TI  - Neural cell adhesion molecule differentially interacts with isoforms of the
      fibroblast growth factor receptor.
AB  - The fibroblast growth factor receptor (FGFR) can be activated through direct
      interactions with various fibroblast growth factors or through a number of cell
      adhesion molecules, including the neural cell adhesion molecule (NCAM). We
      produced recombinant proteins comprising the ligand-binding immunoglobulin-like
      modules 2 and 3 of FGFR1b, FGFR1c, FGFR2b, FGFR2c, FGFR3b, FGFR3c, and FGFR4, and
      found that all FGFR isoforms, except for FGFR4, interacted with NCAM. The binding
      affinity of NCAM-FGFR interactions was considerably higher for splice variant 'b'
      than for splice variant 'c'. We suggest that the expression pattern of various
      FGFR isoforms determines the cell context-specific effects of NCAM signaling
      through FGFR.

PMID- 21876470
TI  - Potential therapeutic applications of mesenchymal stromal cells.
AB  - Mesenchymal stromal cells (MSCs) are a non-homogeneous population of plastic
      adherent cells which were initially isolated from post-natal bone marrow. They
      have the capacity to differentiate to multiple mesodermal lineages including
      bone, cartilage and adipose tissue. In stringent culture conditions, MSCs can
      also be induced to differentiate into different cell types of endoderm and
      neuroectoderm lineages. To date, no specific marker identifies MSCs, although a
      number of cell surface antigens have been described which enrich for MSCs.
      Mesenchymal stromal cells possess a number of properties which have generated
      considerable interest in diverse cellular therapeutic applications. The capacity
      of MSCs to differentiate into multiple different cell lineages has seen them
      actively explored for tissue repair, particularly in cardiac, orthopaedic and
      neurological applications. A large body of data indicates that MSCs possess
      immunomodulatory properties. Mesenchymal stromal cells are immunosuppressive,
      interacting with T lymphocytes, antigen presenting cells, B lymphocytes, and
      natural killer cells. In addition, they are immunoprivileged, allowing
      transplantation across allogeneic barriers. These immunomodulatory properties
      have seen infusion of MSCs for the treatment of steroid refractory graft versus
      host disease, a life threatening complication of haemopoietic cell
      transplantation, with promising results. Furthermore, these immune functions may
      lead to roles in the facilitation of engraftment, induction of tolerance and as
      therapy in autoimmune disease.

PMID- 21876471
TI  - The emerging important role of microRNAs in the pathogenesis, diagnosis and
      treatment of human cancers.
AB  - MicroRNAs are small non-protein-coding RNAs which repress gene expression,
      through base pair matching with messenger RNA (mRNA). A single microRNA is
      capable of regulating hundreds of mRNA sequences. Only a small fraction of the
      over 1000 discovered microRNAs have currently known functions; many are crucial
      in the regulation of genetic signalling, including cellular processes such as
      cellular differentiation, growth, proliferation and death. Dysfunction in
      microRNA signalling is present in all cancers studied thus far, leading to
      overactive oncogenic and underactive tumour suppressor gene signalling. Current
      research is actively pursuing the potential to use microRNAs as diagnostic tools
      and novel therapies in a variety of diseases. This review summarises normal and
      abnormal maturation and function of microRNAs and their role in the pathogenesis
      of various human tumours and highlights how microRNAs may be used as diagnostic
      and treatment tools in human cancers in the future.

PMID- 21876472
TI  - Anatomical pathology is dead? Long live anatomical pathology.
AB  - The standard diagnostic instrument used for over 150 years by anatomical
      pathologists has been the optical microscope and glass slide. The advent of
      immunohistochemistry in the routine laboratory in the 1980s, followed by in situ
      hybridisation in the 1990s, has increased the armamentaria available to the
      diagnostic pathologist, and this technology has led to changed patient management
      in a limited number of neoplastic diseases. The first decade of the 21 century
      has seen an increasing number of publications using proteomic technologies that
      promise to change disease diagnosis and management, the traditional role of an
      anatomical pathologist. Despite the plethora of publications on proteomics and
      pathology, to date there are actually limited data where proteomic technologies
      do appear to be of greater diagnostic value than the standard histological slide.
      Though proteomic techniques will become more prevalent in the future, it will
      need the expertise of an anatomical pathologist to dissect out and validate this
      added information.

PMID- 21876474
TI  - The effect of donor-recipient cytomegalovirus serology on adult liver
      transplantation: a single center experience.
AB  - INTRODUCTION: We investigated the outcomes of adult liver transplants, according
      to their donor-recipient cytomegalovirus (CMV) serology. MATERIALS AND METHODS:
      We included in the study all adult primary liver transplants, from January 1,
      2002, to December 31, 2005. Follow-up was until December 31, 2007. According to
      the donor-recipient CMV serology, patients were divided into positive-negative
      (PN), positive-positive, negative-negative, and negative-positive groups, and all
      received CMV prophylaxis for 4 months posttransplantation. Hepatitis C patients
      received conventional immunosuppression, whereas all other patients received
      either conventional treatment or alemtuzumab (Campath-1H) induction. RESULTS: We
      studied 438 adult liver transplants. Comparisons were made between high-risk
      group patients (PN) versus all others: 5-year patient survival was 74.31% vs.
      78.8%, (P=NS) and graft survival 63.87% vs. 74.77%, (P=0.042). Five-year freedom
      from rejection was 42.84% vs. 51.95% (P=0.036). CMV infection (n=3) or disease
      (n=27) was observed in 30 patients (PN [n=23], positive-positive [n=6], and
      negative-positive [n=1]). Incidence of CMV infection was 9.8% overall and 34.84%
      and 2.5%, respectively, for the PN group versus all others (P=0.0000). Patients
      who received Campath-1H induction did not have an increased incidence of CMV
      infections compared with those who received conventional immunosuppression.
      CONCLUSIONS: In our center, in adult liver transplantation, CMV donor-recipient
      PN serology is associated with rejection, graft survival, and CMV infection but
      is not correlated with patient survival, Epstein-Barr virus (EBV) occurrence, or
      viral hepatitis recurrence. The introduction of more potent induction
      immunosuppression did not accentuate these negative outcomes.

PMID- 21876475
TI  - Improved islet yield and function by use of a chloride channel blocker during
      collagenase digestion.
AB  - BACKGROUND: Protection of pancreatic islets during isolation procedures is
      mandatory for successful islet transplantation. Chloride channel inhibition has
      been reported to prevent cell death induced by various stimuli. We examined the
      effects of the chloride channel blocker, 4,4'-diisothiocyanatostilbene-2,2'
      disulfonic acid disodium salt (DIDS) and extracellular Cl(-)-free conditions on
      islet isolation outcomes. METHODS: Experimental groups were created based on the
      collagenase solutions used for Wistar rat islet isolation: control group, Hanks'
      balanced salt solution; DIDS group, 200 MUM DIDS; and Cl(-)-free group, sodium
      gluconate substituted for sodium chloride. We determined whether collagenase
      digestion induced the death of islet cells through Cl(-) influx into the cells.
      We then assessed islet yield and the viability of isolated islets. RESULTS: We
      observed an increase in intracellular Cl(-) concentration under collagenase
      digestion conditions using a Cl(-)-sensitive fluorescent dye and subsequent
      rupture of islet cells. Consequently, islet yields were significantly higher in
      the DIDS and Cl(-)-free groups than in the control group, and islet morphology of
      the former groups was preserved. Of streptozotocin-induced diabetic severe
      combined immunodeficiency mice transplanted with a marginal dose of islets, all
      seven mice in the DIDS group and six of the seven mice in the Cl(-)-free group
      became normoglycemic, compared with two of seven mice in the control group
      (control vs. DIDS, P=0.010; control vs. Cl(-) free, P=0.051). CONCLUSION: Our
      results indicate that DIDS inhibition of Cl(-) influx into islets protects islets
      during digestion procedures, offering a new strategy for the improvement of islet
      isolation outcomes.

PMID- 21876473
TI  - Confirmation of prior evidence of genetic susceptibility to alcoholism in a
      genome-wide association study of comorbid alcoholism and bipolar disorder.
AB  - OBJECTIVES: Alcoholism and affective disorders are both strongly comorbid and
      heritable. We have investigated the genetic comorbidity between bipolar affective
      disorder and alcoholism. METHODS: A genome-wide allelic association study of 506
      patients from the University College London bipolar disorder case-control sample
      and 510 ancestrally matched supernormal controls. One hundred forty-three of the
      bipolar patients fulfilled the Research Diagnostic Criteria diagnosis of
      alcoholism. A total of 372 193 single nucleotide polymorphisms (SNPs) were
      genotyped. Genes previously shown to be associated with alcoholism and addiction
      phenotypes were then tested for association in the bipolar alcoholic sample using
      gene-wise permutation tests of all SNPs genotyped within a 50-kb region flanking
      each gene. RESULTS: Several central nervous system genes showed significant
      (P<0.05) gene-wise evidence of association with bipolar alcoholism. The genes
      implicated, which replicated genes previously shown to be associated with
      alcoholism were: cadherin 11, collagen type 11 alpha2, neuromedin U receptor 2,
      exportin7, and semaphorin-associated protein 5A. The SNPs most strongly
      implicated in bipolar alcoholism, but, which did not meet conventional genome
      wide significance criteria were the insulin-like growth factor-binding protein 7,
      carboxypeptidase O, cerebellin 2, and the cadherin 12 genes. CONCLUSION: We have
      confirmed the role of some genes previously shown to be associated with
      alcoholism in the comorbid bipolar alcoholism subgroup. In this subgroup, bipolar
      disorder may lower the threshold for the phenotypic expression of these
      alcoholism susceptibility genes. We also show that some genes may independently
      increase susceptibility to affective disorder and alcoholism.

PMID- 21876476
TI  - Effect of cinacalcet on renal electrolyte handling and systemic arterial blood
      pressure in kidney transplant patients with persistent hyperparathyroidism.
AB  - BACKGROUND: The calcimimetic cinacalcet has recently been increasingly used for
      persistent hyperparathyroidism after renal transplantation. The present study
      investigated the short-term effects of cinacalcet on urinary electrolyte
      concentration and arterial blood pressure in kidney transplant patients with
      persistent hyperparathyroidism. METHODS: In a prospective controlled single
      center cross-over study, we examined 10 stable kidney transplant patients (mean
      estimated glomerular filtration rate 51+/-10 mL/min/1.73 m(2)) who received
      cinacalcet daily for persistent hyperparathyroidism. Urine specimens were
      collected at baseline and every 2 hr for a total study period of 6 hr after
      ingestion of 30 mg cinacalcet and without cinacalcet. Intact parathyroid hormone
      was determined at baseline and 2 hr later. Using ambulatory blood pressure
      measurement, arterial blood pressure was determined every 15 min. RESULTS: Intact
      parathyroid hormone was significantly reduced with cinacalcet as compared with
      controls (-37+/-27.7% vs. -9.6+/-10.3%, P=0.009). With cinacalcet, urinary
      calcium and magnesium concentration were increased (P=0.042 and P=0.007,
      respectively) and differed significantly as compared with the control phase
      without cinacalcet. After 4 hr, an increased urinary sodium concentration was
      also found compared with the control phase (P=0.039). Systolic blood pressure was
      reduced with cinacalcet (P<0.001) and differed significantly from control phase (
      13.7+/-9.9 mm Hg vs. -3.2+/-5.2 mm Hg after 2 hr, P=0.009; -18.1+/-10.8 mm Hg vs.
      -1.9+/-5.2 mm Hg after 4 hr, P=0.001). CONCLUSIONS: In the short term, cinacalcet
      increases the urinary concentration of calcium, magnesium, and sodium. The
      observed antihypertensive effect might be beneficial in patients with a high
      cardiovascular risk after kidney transplantation.

PMID- 21876477
TI  - Validation of urinary CXCL10 as a marker of borderline, subclinical, and clinical
      tubulitis.
AB  - BACKGROUND: Renal allograft injury secondary to subclinical and clinical
      tubulitis remains an important cause of allograft fibrosis and loss despite
      modern immunosuppression. The goal of this study was to validate the previously
      reported use of urinary CXCL10 (interferon-gamma-induced protein of 10 kDa) as a
      noninvasive marker of tubulitis in an independent clinical cohort. METHODS: Urine
      samples (n=102) from 91 patients with protocol or indication biopsies were
      assayed for urinary CXCL10 using ELISA. The groups analyzed were as follows:
      normal histology (n=22); interstitial fibrosis and tubular atrophy (IFTA) (n=20);
      IFTA and borderline tubulitis (n=13); borderline (n=13), subclinical (n=17); and
      clinical tubulitis (n=17) without IFTA. RESULTS: The ratio of urinary CXCL10 to
      creatinine (CXCL10: Cr) was found to distinguish borderline, subclinical and
      clinical tubulitis from normal histology, and IFTA. The area under the curve
      receiver operating characteristic curve to distinguish normal versus borderline
      and subclinical tubulitis was 0.845 (OR 1.407, P=0.0184); normal versus
      borderline, subclinical and clinical tubulitis was 0.835 (OR 1.400, P=0.0127).
      CXCL10: Cr demonstrated a sensitivity of 73.3% and specificity of 72.7% for
      normal versus borderline and subclinical tubulitis at a cut-off of 1.97 ng
      CXCL10/mmol Cr. CONCLUSION: This study validates urinary CXCL10 as a noninvasive,
      sensitive, and specific marker for tubulitis in an independent cohort. The
      straightforward urine processing is accessible to clinical laboratories. We
      propose that CXCL10 may be useful as a supplementary noninvasive screening test
      for tubulitis in renal transplant patients, with a level more than 1.97 ng
      CXCL10/mmol Cr being a threshold to consider biopsy.

PMID- 21876478
TI  - BK virus infection and its effect on renal function in pediatric liver-transplant
      recipients: a cross-sectional, longitudinal, prospective study.
AB  - BACKGROUND: Chronic renal failure (CRF) is a well-documented complication of
      liver transplantation. BK virus (BKV) is a common cause of CRF in renal
      transplant recipients and has been sporadically associated with renal failure
      after nonrenal solid-organ transplantation. The aims of the study were to
      determine the prevalence of BK viruria and viremia in pediatric liver-transplant
      recipients, assess the natural course of BKV infection over time, and examine the
      association between BKV positivity and renal function. METHODS: A prospective,
      cross-sectional study of 59 pediatric liver-transplant recipients. Blood and
      urine samples were collected at enrollment for creatinine level and BKV
      polymerase chain reaction test. BKV-positive patients underwent repeated testing
      and follow-up. The medical files were reviewed for clinical data. RESULTS: Median
      age at enrollment was 11.5 years, and median time from transplantation was 61
      months. One child (1.7%) had viremia, and nine children (15.3%) had viruria
      (median: 610 copies/mL). All cases of viruria/viremia resolved spontaneously,
      nine of them within 10 months. There were no significant differences in
      demographic or clinical variables between the BKV-positive and BKV-negative
      children. None of the BKV-positive patients had evidence of renal dysfunction.
      CONCLUSIONS: Pediatric liver-transplant recipients have a low prevalence of BK
      viruria/viremia. BKV infection is associated with low viral loads and resolves
      spontaneously within a relatively short period, without residua. BKV is not
      associated with CRF postliver transplantation. BKV testing should not be part of
      the routine follow-up of children after liver transplantation.

PMID- 21876479
TI  - Norcantharidin modulates development of dendritic cells and prolongs skin
      allograft survival.
AB  - BACKGROUND: To examine the effects of norcantharidin (NCTD) on development of
      human myeloid dendritic cells (DCs) in vitro and in skin allograft
      transplantation in vivo. METHODS: Human CD14(+) monocytes were isolated and
      triggered differentiation and maturation toward myeloid DCs with and without
      NCTD. The cell morphology, viability, cell death, expression of surface markers
      and co-stimulatory molecules, allostimulatory activity, and cytokine production
      were examined for characterization of DCs. The rejection of mice skin allograft
      model was used to translate the in vitro effect of cantharidin (CTD) and NCTD on
      DCs. RESULTS: DCs developed in the presence of NCTD showed decreased viability,
      cell death with necrosis, and lower expression of CD1a and CD83. DCs triggered in
      the presence of NCTD possessed a greater allostimulatory activity in naive
      CD4(+)CD45RA(+) T cells. NCTD modulated DCs through calcineurin phosphatase but
      not through mammalian target of rapamycin or downstream molecule p70S6 kinase. In
      vivo, NCTD caused accumulation and co-localization of antigen-presenting cells
      and regulatory T cells in the interfollicular area of the recipients' spleens.
      CTD and NCTD prolonged skin allograft survival along with less severe
      histopathological inflammatory reactions. CTD, but not NCTD, treatment caused
      elevation of serum alanine aminotransferase and evident mortality of the
      recipients. CONCLUSION: NCTD modulated the differentiation and maturation of
      human myeloid DCs and caused deviation of standard DC differentiation toward a
      tolerogenic phenotype through calcineurin phosphatase inhibition. In vivo, both
      drugs effectively prolonged skin allograft survival. NCTD was less toxic than
      CTD, and thus, has potential for development as an immunosuppressant for
      transplant rejection.

PMID- 21876480
TI  - Effect of preprocurement ventilation on lungs donated after cardiac death in a
      canine lung transplantation model.
AB  - BACKGROUND: One method of countering chronic lung donor shortages is the practice
      of donation after cardiac death (DCD). However, this technique inevitably leads
      to pulmonary dysfunction related to warm ischemia. One promising method of
      alleviating this problem is ventilation. However, it can rarely be initiated from
      the onset of cardiac arrest, particularly in uncontrolled DCD donors. We
      investigated the protective effect of the last 60 min of ventilation during a 240
      min warm ischemic time. METHODS: We rendered donor dogs cardiac dead and left
      them at room temperature. Six dogs received ventilation with 100% oxygen for 60
      min starting at 180 min after cardiac arrest (ventilation group). Eight dogs
      received no ventilation. Lungs were harvested 240 min after cardiac arrest, then
      transplanted into recipient dogs. At 60 min after reperfusion, the right
      pulmonary artery was ligated, and the function of the left transplanted lung was
      evaluated. RESULTS: In the ventilation group, all six animals survived for 240
      min after reperfusion, whereas in the nonventilation group, only four of eight
      survived. The ventilation group demonstrated significantly better pulmonary
      oxygenation, shunt fraction, and wet-to-dry weight ratio. Furthermore, the
      ventilation group revealed significantly higher levels of high-energy phosphates
      in the lung tissues, fewer apoptotic cells, lower levels of tumor necrosis factor
      alpha and interleukin-8 messenger RNA in the lung tissues, and lower levels of
      interleukin-6 messenger RNA in the serum. CONCLUSION: Our results suggest that
      ventilation during the late phase of the preprocurement period may ameliorate
      ischemia-reperfusion injury in DCD donors.

PMID- 21876481
TI  - Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome
      P450 enzymes using a high throughput assay.
AB  - The extract from Mitragyna speciosa has been widely used as an opium substitute,
      mainly due to its morphine-like pharmacological effects. This study investigated
      the effects of M. speciosa alkaloid extract (MSE) on human recombinant cytochrome
      P450 (CYP) enzyme activities using a modified Crespi method. As compared with the
      liquid chromatography-mass spectrometry method, this method has shown to be a
      fast and cost-effective way to perform CYP inhibition studies. The results
      indicated that MSE has the most potent inhibitory effect on CYP3A4 and CYP2D6,
      with apparent half-maximal inhibitory concentration (IC(50)) values of 0.78 ug/mL
      and 0.636 ug/mL, respectively. In addition, moderate inhibition was observed for
      CYP1A2, with an IC(50) of 39 ug/mL, and weak inhibition was detected for CYP2C19.
      The IC(50) of CYP2C19 could not be determined, however, because inhibition was
      <50%. Competitive inhibition was found for the MSE-treated CYP2D6 inhibition
      assay, whereas non-competitive inhibition was shown in inhibition assays using
      CYP3A4, CYP1A2 and CYP2C19. Quinidine (CYP2D6), ketoconazole (CYP3A4),
      tranylcypromine (CYP2C19) and furafylline (CYP1A2) were ACCESSused as positive
      controls throughout the experiments. This study shows that MSE may contribute to
      an herb-drug interaction if administered concomitantly with drugs that are
      substrates for CYP3A4, CYP2D6 and CYP1A2.

PMID- 21876482
TI  - Antibacterial activity of Aristolochia brevipes against multidrug-resistant
      Mycobacterium tuberculosis.
AB  - The increased incidence of Multidrug-Resistant Mycobacterium tuberculosis (MDR
      MT) requires the search for alternative antimycobacterial drugs. The main aim of
      this study was to evaluate the dichloromethane extract from Aristolochia brevipes
      (Rhizoma) and the compounds isolated from this extract against several
      mycobacterial strains, sensitive, resistant (monoresistant), and clinical
      isolates (multidrug-resistant), using the alamarBlueTM microassay. The extract
      was fractionated by column chromatography, yielding the following eight major
      compounds: (1) 6alpha-7-dehydro-N-formylnornantenine; (2) E/Z-N
      formylnornantenine; (3) 7,9-dimethoxytariacuripyrone; (4) 9-methoxy
      tariacuripyrone; (5) aristololactam I; (6) beta-sitosterol; (7) stigmasterol; and
      (8) 3-hydroxy-alpha-terpineol. The structures of these compounds were elucidated
      by 1H- and 13C- (1D and 2D) Nuclear Magnetic Resonance (NMR) spectroscopy. This
      study demonstrates that the dichloromethane extract (rhizome) of A. brevipes
      possesses strong in vitro antimycobacterial activity against Mycobacterium
      tuberculosis H37Rv (Minimum Inhibitory Concentration value [MIC], 12.5 ug/mL).
      The most active compound against all mycobacterial strains tested was the
      compound aristolactam I (5), with MIC values ranging between 12.5 and 25 ug/mL.
      To our knowledge, this the first report of antimycobacterial activity in this
      plant.

PMID- 21876483
TI  - An emulsion based microarray method to detect the toxin genes of toxin-producing
      organisms.
AB  - Toxins produced by bacteria and fungi are one of the most important factors which
      may cause food contamination. The study of detection methods with high
      sensitivity and throughput is significant for the protection of food safety. In
      the present study, we coupled microarray with emulsion PCR and developed a high
      throughput detection method. Thirteen different gene sites which encode the
      common toxins of several bacteria and fungi were assayed in parallel in positive
      and maize samples. Conventional PCR assays were carried out for comparison. The
      results showed that the developed microarray method had high specificity and
      sensitivity. Two zearalenone-related genes were investigated in one of the ten
      maize samples obtained with this present method. The results indicated that the
      emulsion based microarray detection method was developed successfully and
      suggested its potential application in multiple gene site detection.

PMID- 21876484
TI  - Predictors of asthma severity during the pilgrimage to Mecca (Hajj).
AB  - INTRODUCTION: The annual pilgrimage to Mecca (Hajj) is one of the largest
      gatherings in the world and thus its participants are exposed to various
      communicable and noncommunicable diseases. This provides an opportunity to study
      travel epidemiology. OBJECTIVES: The aim of the study was to estimate the
      predictors of asthma severity during the Hajj. PATIENTS AND METHODS: The study
      cohort was recruited from patients who presented to the emergency department (ED)
      of the King Abdul Aziz Hospital, Mecca, Saudi Arabia, between December 3 and 18,
      2008 (5-20 Dhul-Hijjah 1429 H). We included newly diagnosed and previously
      documented cases presenting with asthma symptoms. Sociodemographic and clinical
      data were collected and the risk factors were assessed. The severity of asthma
      exacerbation was measured according to the National Heart, Lung, and Blood
      Institute guidelines. Data were analyzed using the SPSS software. RESULTS: The
      study involved 58 subjects, including 38 women (65.5%). There were 27 subjects
      (46.6%) with mild asthma attack, 18 (31%) with moderate asthma attack, and no
      cases with life-threatening asthma. Insignificantly increased risk of severe
      asthma attack was observed in the following groups: women, people aged 46-60
      years, pilgrims (hajis) who did not belong to a hajj group, non-hajis,
      illiterates, and nonsmokers - the odds ratio (OR) (95% confidence interval [CI])
      was 3.7 (0.7-18.5), 1.7 (0.5-6.3), 2.4 (0.7-8.5), 5.1 (0.6-44.1), 2.3 (0.7-9.1),
      and 2.0 (0.4-10.4), respectively. Forty-six subjects (79.3%) had a history of
      allergy to components of smoke, detergents, dust, animal dander, and perfumes,
      while only 5 patients (8.6%) had drug allergy. High risk of severe asthma was
      observed in subjects with a history of drug allergy, as well as in obese subjects
      and those who often presented to the ED - OR (95% CI) was 6.5 (0.9-43.9), 18.0
      (4.0-80.7), and 3.1 (0.8-11.5), respectively. CONCLUSIONS: Higher risk of severe
      asthma attack was observed in women, people aged 46-60 years, hajis who did not
      belong to a hajj group, non-hajis, illiterates, nonsmokers, obese patients, and
      those who often presented to the ED within the previous 12 months due to asthma
      exacerbation.

PMID- 21876485
TI  - Veratridine induced absence like-seizure in the freely moving rats: a study
      correlating the behavioural findings with the electrophysiological activities.
AB  - OBJECTIVES: Veratridine was characterized previously as an experimental model of
      epilepsy in vitro. The aim of this preliminary investigation is to identify the
      pattern of seizure induced by this model in vivo. MATERIAL AND METHODS:
      Veratridine (200 MUg/kg) was administered intraperitoneally to male Sprague
      Dawley rats and the electrical activity of the brain was recorded as surface
      electroencephalogram (EEG). RESULTS: The animals developed behavioral effects
      manifested as grooming, masticatory movements, facial automatism and wet dog
      shakes (WDSs). There were episodes of complete quiescent periods for 2-5 minutes
      before the animals presumed activity which were repeated every 15-20 minutes. The
      seizure activity during this silent activity showed fast frequency signals in the
      surface EEG correlating with absence seizure. The WDS behaviour was associated
      with electrical spikes on the EEG. When the rats were pre-treated with 200mg/kg
      ethosuximide (ETX), EEG recordings did not display the same fast frequency signal
      as that observed in animals receiving veratridine only. The number and duration
      of WDSs were not altered by ETX (200-400 mg/kg). CONCLUSION: Veratridine produced
      an absence like-seizure activity in the surface EEG, sensitive to ETX and
      correlates with its behavioural effects.

PMID- 21876486
TI  - Utilisation of iodine from different sources by sows and their progeny.
AB  - OBJECTIVES: The aim of the study was to compare iodine utilization from different
      sources by sows and their progeny and the levels of T3 and T4 in their serum.
      DESIGN: Pregnant Czech Large White * Landrace sows were fed with an experimental
      KPK diet (a diet for lactating sows) 14 days before parturition until weaning (at
      a piglet age of 28 days). In group A (n=50, 10 sows, 40 piglets) the feed was
      supplemented with KI (0.6 mg of iodine per kg of feed). Iodine enriched alga
      Chlorella spp. (0.6 mg of iodine per kg of feed) was used as a supplement in
      group B (n=50, 10 sows, 40 piglets). In group C (n=50, 10 sows, 40 piglets) the
      sows were injected i.m. with IFAE at a dose of 100 mg of iodine per sow. Iodine,
      T3 and T4 were measured in each group for comparison of iodine utilization.
      RESULTS: The use of IFAE resulted in higher serum concentrations in sows compared
      to KI and alga. In contrast, iodine concentrations in milk and piglets were lower
      when IFAE were used. We found a wide variation in the concentrations of T3 and T4
      in the serum of piglets in all groups. CONCLUSION: Our results indicate a good
      utilization of iodized oil by sows. However, its transfer into milk is lower
      compared to the other iodine sources.

PMID- 21876487
TI  - Transverse testicular ectopia with abnormal karyotype - a case report.
AB  - OBJECTIVES: Growth disturbances and developmental malformations of external
      genitalia, such as hypospadias, bifid scrotum and micropenis, coexisting with non
      palpable testes, may develop as a result of primary endocrinological dysfunctions
      as well as an effect secondary to chromosomal aberrations. Therefore, patients
      with these symptoms require specific diagnostic and therapeutic approaches.
      DESIGN AND METHODS: We present an example of TTE as a presentation of karyotype
      abnormalities. Clinical presentation - 9.5 year old boy presented with
      hypospadias, bilateral cryptorchidism and right inguinal hernia and short
      stature. RESULTS: Endocrine test showed low testosterone levels with adequate
      gonadal response. Laparoscopy was performed and revealed the presence of TTE.
      CONCLUSIONS: The presence of mosaic karyotype with abnormal Y chromosome does not
      exclude a possibility of testis migration disorders, including TTE, caused by
      other (possibly genetic) factors. Laparoscopy is a technique of choice for
      diagnosis and treatment in cases of cryptorchidism.

PMID- 21876488
TI  - Theta-burst transcranial magnetic stimulation over the supplementary motor area
      decreases variability of temporal estimates.
AB  - OBJECTIVES: Supplementary motor area (SMA) was suggested to have a dominant role
      in the temporal control of behavior by many neuroimaging studies. The aim of this
      study was to support this hypothesis by influencing time estimates with theta
      burst transcranial magnetic stimulation (TMS) over the SMA. METHODS: Nineteen
      healthy volunteers with a mean age 25.9+/-3 (SD) years performed the time
      reproduction task (TRT) before and after 190 seconds of intermittent theta-burst
      TMS over SMA and the precuneus (total 600 pulses). The TRT consisted of an
      encoding phase (during which visual stimuli with durations of 5, 10 and 16.82
      seconds were presented pseudorandomly) and a reproduction phase (during which
      interval durations were reproduced by pressing a button). Mean subjects' interval
      estimates as a measure of accuracy and standard deviation as a measure of
      variability pre-TMS and post-TMS were compared. RESULTS: Theta-burst TMS over
      both areas had no effect on the accuracy of duration estimates. An increased
      variability of interval reproduction was present after stimulation of the
      precuneus (p<0.01) with the biggest effect on the five second interval.
      Stimulation of SMA caused a decrease of variability in the ten second interval
      only (p<0.05). CONCLUSION: It is likely that increased variability of time
      estimates is a non-specific result of impaired attention and working memory after
      theta-burst TMS. Decreased variability after stimulation over the SMA could be
      explained in terms of enhanced activity of the physiological oscillator with a
      frequency close to 0.1 Hz.

PMID- 21876489
TI  - The possible role of the PK1 and its receptor in the etiology of the
      preeclampsia.
AB  - OBJECTIVE: Preeclampsia (PE) is a hypertensive complication of the pregnancy. In
      our study we investigated the expression, localization, and signaling pathways of
      PK1 and PKR1 in third-trimester human placenta and myometrium and assessed the
      correlation between the PK1 and PKR1 expression and signaling and the incidence
      of the PE. MATERIALS & METHODS: We designed two study groups: pregnant PE
      patients and healthy, pregnant women. After collection, tissue was placed in
      RNAlater for RNA extraction, fixed in 4% neutral buffered formalin, and wax
      embedded for immunohistochemistry or placed in RPMI and transported to the
      laboratory for in vitro culture. We have collected and processed placental and
      myometrial biopsies from 40 patients - 19 were PE patients. RESULTS: Only the PK1
      mRNA expression comparison between PE and CTRL in placenta showed statistically
      significant difference (p=0.004). There was statistically significant difference
      in cell signaling in myometrium controls in 30 minutes after ligand. The rise in
      pERK/tERK ratio is clearly visible in time intervals 20 and 30 minutes in
      controls, although with no statistical significance. There was no difference in
      PK1 and PKR1 localization in the placenta and myometrium in the groups.
      CONCLUSIONS: The number of PKR1 is not reduced in PE. The reduced PK1 mRNA
      expression is not than dependent on PKR1 mRNA expression. The data shows that ST
      produces much more PK1 in healthy pregnant women than those suffering from PE. We
      can conclude that in PE the production of PK1 is impaired and so are the
      endocrine functions of the ST.

PMID- 21876490
TI  - The genospecies B. burgdorferi s.l., isolated from ticks and from neurological
      patients with suspected Lyme borreliosis.
AB  - OBJECTIVE: Lyme borreliosis (LB) is the most disseminated tick-borne disease in
      the Northern hemisphere, and infestation with ticks is one of the essential
      factors influencing transmission of the disease to humans. This work intends to
      compare the occurrence of borrelia circulating in indigenous ticks and in
      patients suffering from neurological diseases. MATERIALS & METHODS: The total of
      660 nymphs and 567 adult ticks from the Bratislava and Kosice areas was examined
      over the years 2001-2004, and the cerebrospinal fluid (CSF) of 82 neurological
      patients suffering from suspected Lyme borreliosis infection was investigated in
      the 2007-2009 period, using the polymerase chain reaction method (PCR). RESULTS:
      PCR investigation proved presence of borrelia in 23.3% of the total 1227 ticks;
      of these, co-infection was found in 2.7% of all ticks. Borrelia garinii (9.9%)
      and B. valaisaina (9.2%) were the prevalent types. PCR investigation of the CSF
      samples of 32 patients with clinically diagnosed Lyme borreliosis showed the
      presence of B. burgdorferi s.l. in 17 cases. Positive results were found also in
      patients with unclear or different diagnoses. In cases where the genospecies
      could be identified, B. garinii was most frequently found (8x), followed with B.
      burgdorferi s.s. (4*) and B. afzelii (3*). CONCLUSIONS: The high infestation
      level of ticks with borrelia, mainly with B. garinii which is the most-often
      documented borrelia species identified in neurological patients, is indicative of
      a high risk of this contamination in Slovakia. B. garinii were found also in our
      neuroborreliosis patients, whereas their proof in the CSF of patients with
      suspected neuroborreliosis or with a different clinical diagnosis pointed upon
      their persistence after an infectious experience. However, knowledge of not only
      the genospecies but also of the genotypes capable of eliciting an invasive
      disorder would be necessary for better clarification of the relationship between
      borrelia and their peccant capacity. Identification of the invasive borrelia
      types circulating in nature, and clarification of the vector vs. human infection
      incidence relationship is of importance from the aspect of detailed knowledge of
      the epidemiology of this disease.

PMID- 21876491
TI  - Solid papillary carcinoma of the breast with neuroendocrine features in a
      pregnant woman: a case report.
AB  - Solid papillary carcinoma, a special form of breast carcinoma with neuroendocrine
      differentiation, usually presents in women aged 60 years or more. (Koern 2010).
      According to our best knowledge, we present the second case of such a tumor in
      pregnant women.

PMID- 21876492
TI  - Selected diabetes control indicators and working memory efficacy.
AB  - OBJECTIVES: The goal of the study was an evaluation of differences in working
      memory effectiveness between patients with type 1 and type 2DM. It was also
      attempted to ascertain whether the level of diabetes control is associated with
      working memory effectiveness. METHODS: 62 subjects were enrolled into the study.
      All patients were divided into two groups: patients with type 1DM (n=31) and with
      type 2DM (n=31). The Trail Making Test (TMT) and the Stroop Test were used for
      evaluation of working memory effectiveness. Diabetes control indicators included:
      glycated haemoglobin (HbA1C) level, total cholesterol concentration, HDL and LDL
      cholesterol concentration and body mass index (BMI). RESULTS: The patients with
      type 1DM obtained a significantly lower time in the execution of TMT, part B
      (p=0.01) and of RCNb (p=0.01) and NCWd (p=0.01) versions of the Stroop Test,
      while making significantly less errors in NCWd version (p=0.01). Significant
      correlations were demonstrated between BMI values and the rate of execution of
      TMT, part B (p=0.03), as well as the rate of execution of RCNb (p=0.04) and NCWd
      (p=0.01) versions of the Stroop Test. Total cholesterol level was significantly
      correlated with the rate of execution of TMT, part A (p=0.04) and B (p=0.01). No
      significant correlations were found between cholesterol fraction levels in blood
      of the studied patients and the results of performed tests, with one exception,
      regarding the relationship between LDL cholesterol fraction and the rate of the
      Stroop Test execution in RCNb version (p=0.04). CONCLUSIONS: 1). Higher working
      memory efficacy was demonstrated among the patients with type 1DM vs. those with
      type 2DM. 2). The level of diabetes control is an influential factor for working
      memory effectiveness in diabetic patients.

PMID- 21876493
TI  - Plasma dehydroepiandrosterone-sulphate is related to personality and stress
      response.
AB  - OBJECTIVES: Dehydroepiandrosterone-sulphate (DHEAS) physiologic relevance remains
      controversial. However, several central nervous system and behavioural effects of
      DHEAS have been described. We explored the relation between DHEAS and both
      pituitary-adrenal axis reactivity and personality in human subjects. DESIGN: We
      studied 120 consecutive patients assisted at the out patient endocrine department
      of a public central hospital before medical treatment. Personality was evaluated
      with the Minnesota Multiphasic Personality Inventory (MMPI) and the pituitary
      adrenal axis reactivity was assessed with the CRH test. RESULTS: Baseline DHEAS
      was inversely related to peak/basal cortisol (parcial r=-0.454, p<0.05) response
      to CRH infusion. DHEAS reactivity in the CRH test was directly related to the
      Deviant Behaviour triad (BD) (r=0.257, p<0.05) and type A personality (AP)
      (r=0.295, p<0.05). Basal ACTH was directly related to baseline DHEAS (r=0.366,
      p<0.001) and together with age and gender explained 34% of DHEAS variability.
      CONCLUSIONS: DHEAS may be a protective factor against an excessive cortisol
      response when people are under stress situations. Personality may be related to
      DHEAS reactivity.

PMID- 21876494
TI  - Neuroeconomics of suicide.
AB  - Suicidal behavior is a leading cause of injury and death worldwide. Suicide has
      been associated with psychiatric illnesses such as depression and schizophrenia,
      as well as economic uncertainty, and social/cultural factors. This study proposes
      a neuroeconomic framework of suicide. Neuroeconomic parameters (e.g., risk
      attitude, probability weighting, time discounting in intertemporal choice, and
      loss aversion) are predicted to be related to suicidal behavior. Neurobiological
      and neuroendocrinological substrates such as serotonin, dopamine, cortisol (HPA
      axis), nitric oxide, serum cholesterol, epinephrine, norepinephrine, gonadal
      hormones (e.g., estradiol and progesterone), dehydroepiandrosterone (DHEA) in
      brain regiouns such as the orbitofrontal/dorsolateral prefrontal cortex and
      limbic regions (e.g., the amygdala) may supposedly be related to the
      neuroeconomic parameters modulating the risk of suicide. The present framework
      puts foundations for "molecular neuroeconomics" of decision-making processes
      underlying suicidal behavior.

PMID- 21876495
TI  - Medullar thyroid carcinoma in mediastinum initially presenting as Ectopic ACTH
      syndrome. A case report.
AB  - A rare case with ectopic adrenocorticotrophic hormone syndrome (EAS) caused by
      medullar thyroid carcinoma (MTC) in mediastinum was reported. This 49 year-old
      male patient initially presented with serious and intractable hypokalemia.
      Endocrine evaluations showed increased levels of adrenocorticotrophic hormone
      (ACTH) and urinary free cortisol, which could not be suppressed more than 50% by
      high-dose dexamethasone suppression test. Computed tomography (CT) scan detected
      a 5*5*5 cm mass at the bottom of thyroid in anterior mediastinum. The patient
      underwent total thyroidectomy with central compartment and ipsilateral modified
      radical neck dissection. Pathological examination showed an infiltrating thyroid
      medullary carcinoma with abundant amyloid deposition, meanwhile
      immunohistochemical positive for ACTH. After surgery, serum levels of kalium, as
      well as cortisol and ACTH returned to normal range. During follow-up, the
      patient's clinical manifestation of Cushing syndrome relieved.

PMID- 21876496
TI  - Mathematical modelling the systemic regulation of blood glucose: 'a top-down'
      systems biology approach.
AB  - The objective of this article is to review the mechanisms which the body uses to
      regulate its function. The author considers, in particular, the nature and
      structure of the physiological systems with a specific focus upon the systemic
      regulation of blood glucose and highlights an innovative technology, based upon
      the top-down cognitive approach, which incorporates a unique mathematical model
      of the physiological systems and autonomic nervous system. Most systems biology
      is a development of the prevailing reductionist biomedical paradigm. It adopts a
      bottom-up approach seeking systemic justification for biochemical and biophysical
      research findings. By contrast the 'top-down' approach considers the neural
      regulation of the physiological systems and the neurological, cognitive and
      biochemical consequences of systemic dysfunction i.e. the consequences of sensory
      input upon the neural regulation of the body's systems, organs, and its cellular
      and molecular biochemistry. In conclusion, the evidence suggests that the onset
      and progression of Diabetes Mellitus cannot be accurately assessed by individual
      biomedical indices but instead that the regulation of blood glucose is one of a
      number of inter-related physiological systems which act in a coordinated manner
      in order to maintain the body's physiological stability.

PMID- 21876497
TI  - Marburg variant multiple sclerosis - a case report.
AB  - In this case report we describe the case of a 24 year-old female with a fulminant
      demyelinating disease of white matter. Disease progression was most probably
      consistent with the Marburg variant (malignant form) of multiple sclerosis with
      rapid deterioration of the patient's clinical condition, including bulbar
      symptoms and epileptic paroxysms and ending with persistent coma and
      tetraparesis, over the course of 6 months from first symptoms. Repeated Magnetic
      Resonance Imaging (MRI) examination showed progression of multiple demyelinating
      lesions culminating in a contiguous focal disorder of the white matter extending
      both supratentorially and infratentorially. The serial MRI changes closely mapped
      the deterioration in the patients clinical status. Our patient showed no response
      to repeated pulse corticotherapy, administration of intravenous immunoglobulins,
      serial plasmapheresis, and combined high-dose pulse immunosuppression (specify
      what was used here) and mitoxantrone.

PMID- 21876498
TI  - Mammary invasive ductal adenocarcinoma and vulvar invasive keratinizing squamous
      cell carcinoma in a woman with disseminated discoid lupus erythematosus (DDLE) -
      a case review.
AB  - A case of metachronous presentation of two malignancies, invasive mammary ductal
      adenocarcinoma and later invasive keratinizing squamous cell vulvar carcinoma,
      complicating a 20 years long course of disseminated discoid lupus erythematosus
      is described. The authors underline a potential role of long-standing
      immunotherapy as a factor responsible for inducing secondary neoplasia.

PMID- 21876499
TI  - Lipoprotein profile in patients who survive a stroke.
AB  - OBJECTIVE: In the subjects, who survived a stroke, an atherogenic lipoprotein
      profile phenotype B, was identified and a predominance of atherogenic
      lipoproteins of the lipoprotein families, VLDL and LDL, in the lipoprotein
      spectrum, was confirmed. The higher total cholesterol, triglycerides, and low HDL
      concentrations were accompanied by high serum levels of small dense LDL - strong
      atherogenic subfractions of the LDL family. High LDL2 also contributes to the
      creation of the atherogenic lipoprotein profile. Conversely, decreased serum
      concentration of LDL1 suggests, that the LDL1 subfraction does not contribute to
      the creation of an atherogenic lipoprotein profile of specific individuals, i.e.,
      those who survived a stroke. MATERIALS AND METHODS: A quantitative analysis of
      serum lipoproteins in a group of stroke patients, and in a group of healthy
      normolipidemic volunteers, without signs of clinically manifested impairment of
      the cardiovascular system, was performed. For the analysis of plasma
      lipoproteins, an innovative electrophoresis method was used, on polyacrylamide
      gel (PAG) - the Lipoprint LDL system, (Quantimetrix corp., CA, USA). With regard
      to lipids, total cholesterol and triglycerides in serum were analyzed with an
      enzymatic CHOD PAP method (Roche Diagnostics, FRG). A new parameter, the score
      for anti-atherogenic risk (SAAR), was calculated as the ratio between non
      atherogenic to atherogenic serum lipoproteins in examined subjects. RESULTS: An
      atherogenic lipoprotein profile phenotyp B was identified in the individuals who
      survived a stroke. There were increased concentrations of total cholesterol,
      triglycerides (p<0.001), and atherogenic lipoproteins: VLDL (p<0.001), total LDL,
      LDL2 (p<0.0001) and LDL3-7 (p<0.01), in the group of stroke patients, compared to
      the control group. The LDL1 subfraction, like HDL, was decreased and did not
      contribute to the formation of the atherogenic lipoprotein spectrum in stroke
      surviving individuals. Therefore, it can be assumed that the LDL1 subfraction is
      not an atherogenic part of the LDL family, which was usually considered to be an
      atherogenic lipoprotein part of the lipoprotein spectrum. Decreased SAAR values -
      score of anti-atherogenic risk, was confirmed in the stroke surviving
      individuals, compared to the controls, with high statistical significance
      (p<0.0001). CONCLUSIONS: The advantages of this new method include: (i)
      Identification of an atherogenic and a non-atherogenic lipoprotein profile, in
      the serum of examined individuals. (ii) Identification of an atherogenic
      normopidemic lipoprotein profile; phenotype B in subjects who survived a stroke.
      (iii) Introduction of new risk measure, the score for anti-atherogenic risk
      (SAAR), to estimate the atherogenic risk of examined individuals. (iv)
      Declaration of an atherogenic lipoprotein profile is definitive when small dense
      LDL are present in serum. It is valid for hyperlipidemia and for normolipidemia
      as well. (v) Selection of optimal therapeutic measures, including removal of
      atherogenic lipoproteins, as a part of a complex therapeutic approach, and the
      secondary prevention of a relapsing ischemic cerebral-vascular event.

PMID- 21876500
TI  - Lack of association between the Val158Met catechol-O-methyltransferase gene
      polymorphism and methamphetamine dependence.
AB  - OBJECTIVES: About 25,000 serious methamphetamine abusers live in the Czech
      Republic among the total population of 10 million. Dependence on methamphetamine
      is markedly related to the brain neurotransmitter dopamine, metabolised by
      catechol-O-methyltransferase enzyme. The main aim of the study was to ascertain
      whether the Val158Met catechol-O-methyltransferase gene polymorphism is
      associated with methamphetamine dependence in this Central European country.
      METHODS: One hundred and twenty-three subjects dependent on methamphetamine
      (women N=44), parents of sixty-seven dependent individuals, and four hundred
      healthy controls (women N=250) were involved into the study. We performed a
      population-based as well as family-based genetic association studies. RESULTS: We
      did not find any significant association between the Val158Met catechol-O
      methyltransferase gene polymorphism and methamphetamine dependence using the
      population-based or family-based design (p=0.41-0.66; Chi-Square Test or UNPHASED
      program, Version 3.1.4, respectively). We found a trend toward a statistically
      significant difference between the Val allele carriers and Met/Met homozygotes in
      the frequence of psychotic symptoms induced by methamphetamine (more frequent in
      Val carriers; p=0.062; Chi-Square Test). CONCLUSION: Further research involving
      haplotype analysis and other dopamine-related genetic polymorphisms in large
      populations is needed. More attention should also be paid to possible role of the
      Val158Met catechol-O-methyl-transferase gene polymorphism in individual clinical
      subtypes of dependence on methamphetamine involving e.g. psychotic features or
      violence.

PMID- 21876501
TI  - Is mid-gestational cervical length measurement as sensitive prediction factor of
      preterm delivery in IVF as in spontaneous singleton pregnancies?
AB  - OBJECTIVES: To verify the relation between pregnancy duration and cervical length
      (CL) at 22-24 wks of spontaneous and IVF singleton gestations and to assess its
      predictive value for preterm delivery (< 37 wks). MATERIAL & METHODS: CL at 22-24
      wks was performed according to FMF recommendations in 344 women who conceived
      spontaneously and in 107 IVF singleton pregnancies. The results of CL in both
      groups were divided into subgroups: <= 29 mm, 30-34 mm; 35-39 mm; 40-44 mm; 45-49
      mm and >= 50 mm. They were subsequently correlated with mean durations of
      gestation within subgroups and parameters of accuracy were calculated.
      Correlation and regression analysis was performed. RESULTS: The average age of
      women in both groups was 28.1 y.o. (SD=4.2 years) and 33.4 y.o. (SD=4.1 years),
      respectively. The mean gestation age at delivery was 38.9 wks (SD=2.1 wks) vs.
      37.9 wks (SD=2.3 wks) and the rate of prematurity equaled 7% vs. 15%,
      respectively. Regardless the method of conception there is a positive correlation
      between the CL and the duration of gestation. The regression analysis showed that
      the significant increase in pregnancy duration was correlated with CL >= 35 mm
      (correlation coefficient greater for spontaneous vs. IVF: rxy=0.418 vs rxy=0.341;
      p<0.001). All CL parameters of accuracy were better for spontaneous in comparison
      to IVF pregnancies. CONCLUSIONS: IVF singleton pregnancy carries additional risk
      factors for preterm delivery. Therefore mid-gestational cervical length is less
      sensitive predictor than in spontaneous singleton gestations.

PMID- 21876502
TI  - Interleukin-6 and verbal memory in recurrent major depressive disorder.
AB  - OBJECTIVE: To evaluate the possible association between peripheral levels of
      interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) with immediate
      and delayed verbal recall in a group of recurrent depressed women. METHODS:
      Logical Memory Subtests of the Wechsler Memory Scale - Revised was administered
      to 30 patients with recurrent major depressive disorder with no clinical and
      psychiatric comorbidities. Blood samples were collected from 8:00 am to 9:00 am,
      before memory assessments.Plasma was stored and ELISA assay was used to detect IL
      6 and TNF-alpha levels. RESULTS: There was a statistically significant
      association between IL-6 levels and immediate verbal recall (IVR) (B=-0.787,
      p=0.000) and delayed verbal recall (DVR) (B=-0.695, p=0.001) even after
      controlling for age, depression severity and body mass index. CONCLUSION: The
      results of this study indicated that low performances in IVR and DVR are
      associated with higher IL-6 levels in women with recurrent MDD. The results of
      this study suggest the existence of an association between inflammatory imbalance
      and cognitive impairment in MDD.

PMID- 21876503
TI  - Infection with B. burgdorferi s.l., and the CNS demyelinating disease. A case
      report.
AB  - The work describes three cases of patients at various ages, diagnosed for CNS
      demyelinating disease. The presence of specific antibodies to B. burgdorferi
      sensu lato, and findings of B. burgdorferi s.l. DNA, identified in one case as
      the genospecies B. garinii in the liquor, indicated previous experience with the
      infection. Presumably, persistence of borrelia in the organism could act as one
      of the autoimmune process triggers, resulting in the demyelinating disease.

PMID- 21876504
TI  - Immunotherapy of cervical cancer as a biological dissipative structure.
AB  - Cervical cancer can be not only prevented, but also effectively treated.
      Decreased efficiency of biochemical, neurohormonal and/or immunological
      mechanisms leads to infectious states which, irrespective of their bacterial,
      viral or parasitic aetiology, are only the necessary, but not the sufficient
      causes of neogenesis. The cause of cancer is the natural and common phenomenon of
      the self-organization of systems, endangered by ending of their existence, into
      more efficient time-space structures at the expense of their surrounding.
      Infected cells or infectiously changed tissues in their final phase of existence
      are often recognized as a precancerous state, but their genome does not differ
      from other organism cells, and that is why the carcinogenesis can still be
      prevented by direct fighting of pathogenic microorganisms, and indirectly by
      strengthening the body by neurohormonal therapy or vaccine
      immunopotentialization. Primary prophylaxis of neoplasms requires that not only
      the dissipathogenic state of cells be prevented, but also their tissue
      surrounding be normalized to head off the risk of the self-organization of
      neoplastic forms of life, differing in their genetic identity from the
      surrounding cells. Lactovaginal immunopotentialization complements the
      conservative and operative methods of oncological treatment, as well as has
      prophylactic application in women with the history of miscarriages, premature
      deliveries, lack of or significantly shortened lactation, neurohormonal
      menstruating disorders, chronic and recurrent inflammations of the reproductive
      organs, long-term hormonal contraception and hormone replacement therapy during
      menopause, or only deficiency of Lactobacillus vaginalis, as indicators of risk
      of cervical cancer.

PMID- 21876505
TI  - Hormonal regulators of food intake and weight gain in Parkinson's disease after
      subthalamic nucleus stimulation.
AB  - OBJECTIVES: Weight gain has been reported in patients with Parkinson's disease
      (PD) treated with deep brain stimulation of the subthalamic nucleus (STN-DBS). To
      evaluate the influence of STN-DBS on weight changes, we studied food-related
      hormones. DESIGN: Anthropometric parameters and food-related hormones (leptin,
      adiponectin, resistin, ghrelin, cortisol, insulin, and thyroid stimulating
      hormone) were measured in 27 patients with STN-DBS during a 12 month period
      following electrode implantation. RESULTS: Besides marked motor improvements on
      STN-DBS, PD patients significantly gained weight. The mean weight gain at 12
      months was 5.2+/-(SD)5.8 kg. A significant decrease in cortisol levels compared
      to baseline appeared at month 2 and persisted at 12 months (p<0.01, corrected),
      with no significant changes in other hormones tested. CONCLUSIONS: Changes in
      peripheral food-related hormones do not appear to cause weight gain in PD
      patients. Direct effects of STN-DBS on hypothalamic catabolic/anabolic peptide
      balance remain hypothetical and necessitate further elucidation.

PMID- 21876506
TI  - HDL subfractions analysis: a new laboratory diagnostic assay for patients with
      cardiovascular diseases and dyslipoproteinemia.
AB  - OBJECTIVE: The HDL family forms a protective part of plasma lipoproteins. It
      consists of large HDL, intermediate HDL, and small HDL subclasses. The large HDL
      and intermediate HDL subclasses are considered anti-atherogenic parts of the HDL
      family. The atherogenicity of the small HDL subclass is currently the subject of
      much discussion. In the patient group with the diagnosis of cardiovascular
      disease (arterial hypertension, coronary heart disease) and in individuals with a
      non-atherogenic hypercholesterolemia, a type of lipoprotein profile (either a non
      atherogenic phenotype A, or an atherogenic phenotype B) was identified, and a
      concentration of small dense LDL (sdLDL) was analyzed. The aim of this study was
      to identify the major representative of the HDL subclasses in the individuals
      with cardiovascular diseases, who had an atherogenic lipoprotein phenotype B, and
      in the individuals with the diagnosis of non-atherogenic hyper
      betalipoproteinemia LDL1,2, who had a non-atherogenic lipoprotein phenotype A.
      METHODS: Identification of the specific lipoprotein phenotype and a quantitative
      analysis of small dense LDL was performed by an electrophoresis method on
      polyacrylamide gel (PAG), using the Lipoprint LDL system. For a quantitative
      analysis of HDL subclasses, i.e., large HDL, intermediatete HDL, and small HDL,
      in subjects with newly diagnosed cardiovascular diseases (arterial hypertension
      and coronary heart disease), and in subjects with a non-atherogenic
      hypercholesterolemia (hyper-betalipoproteinemia LDL1,2), we used an innovative
      electrophoresis method on polyacrylamide gel (PAG), the Lipoprint HDL system.
      With regard to lipids, total cholesterol and triglycerides in plasma were
      analyzed by an enzymatic CHOD PAP method. A control group consisted of a group of
      healthy normolipidemic volunteers without signs of clinically manifested
      impairment of the cardiovascular system. RESULTS: In the patient group with the
      diagnosis of arterial hypertension (p<0.0002) and coronary heart disease
      (p<0.0001), (both are classified as cardiovascular diseases), the large HDL
      subclass was significantly decreased and the small HDL subclass was increased
      (p<0.0001). The concentration of the intermediate HDL subclass did not differ
      from that of the control group. These results were in accordance with an
      atherogenic lipoprotein phenotype B in individuals with the diagnosis of
      cardiovascular diseases, where, using a Lipoprint LDL analysis, a high
      concentration of atherogenic small dense LDL (p<0.0001) was found. Thus, it seems
      that the small HDL subclass represents an atherogenic part of the HDL family.
      Conversely, an increased concentration of total HDL (p<0.0001), large HDL
      (p<0.005), and intermediate HDL subclasses (p<0.0001) was found in a group of
      subjects with a non-atherogenic hyper-betalipoproteinemia LDL1,2.The
      concentration of the small HDL subclass did not differ from that of the control
      group. In this non-atherogenic lipoprotein profile, only traces of atherogenic
      small dense LDL were identified. CONCLUSIONS: The advantages of this new method
      includes: (i) Identification of ten HDL subfractions with Lipoprint HDL analysis
      (large HDL1-3, intermediate HDL 4-7, and small HDL 8-10) . (ii) Discovery of a
      high concentration of small HDL in plasma lipoproteins in patients with
      cardovascular diseases with an atherogenic lipoprotein phenotype B, confirms that
      the atherogenic subclass of HDL family is attributable to small HDL. (iii)
      Presence of a low concentration of small HDL in non-atherogenic
      hypercholesterolemia also confirms the atherogenic characteristics of the small
      HDL subclass per se. (iv) Presence of small dense LDL is definitive to diagnose
      an atherogenic lipoprotein profile. It is valid for hyperlipidemia and for
      normolipidemia as well.

PMID- 21876507
TI  - Glucocorticoid receptor polymorphism is associated with lithium response in
      bipolar patients.
AB  - OBJECTIVES: Glucocorticoid receptor has been considered in the pathogenesis of
      bipolar disorder as it is an important regulator of the circadian rhythm and HPA
      negative feedback. As glucocorticoid receptor may be possibly related to lithium
      action we aimed to investigate variation in the GR gene in association with
      response to lithium treatment in Polish population of bipolar patients. METHODS:
      We analyzed 115 bipolar patients treated with lithium carbonate for 5-27 years.
      Thirty patients were identified as excellent lithium responders (ER), 58 patients
      as partial responders (PR), and 27 patients were non-responders. Genotypes of
      eight analyzed polymorphisms of GR gene (rs10052957, rs6196, rs6198, rs6191,
      rs258813, rs33388, rs6195, rs41423247) were established by TaqMan SNP Genotyping
      Assays. Statistical analysis was done with Statistica version 9.0. Linkage
      disequilibrium analysis was performed in Haploview v. 4.1. RESULTS: We have found
      significant differences in allele frequencies for BclI polymorphism between
      patients with different lithium response with C allele associated with excellent
      lithium response. For the other GR polymorphisms any significant association with
      different lithium response was found. We observed a strong linkage disequilibrium
      of five GR polymorphisms (rs6198, rs6191, rs6196, rs258813, rs33388), with TAAGA
      haplotype more prevalent in the group of partial- and non-responders to lithium.
      CONCLUSION: The GR gene variation seems to be involved in the response to lithium
      treatment in our group of bipolar patients.

PMID- 21876508
TI  - Genetics in Psychiatry - up-to-date review 2011.
AB  - Psychiatric genetics is a popular and much-discussed topic. Many candidate genes
      have been investigated in relation to psychiatric disorders and many connections
      have been found. The utilization of these investigations is currently at a
      theoretical level. Nevertheless, these findings of candidate genes will be
      important for further research and subsequent clinical use, for example in
      pharmacogenetics). Due to the rapidly growing number of empirical studies that
      provide profound analysis of different genes and their variants in different
      psychiatrical symptomatology, the field is highly divided, and providing a
      succinct overview is challenging. This article attempts to provide an up-to-date
      review of the most important and most discussed genes (mainly transporter and
      receptor genes) contributing to the etiology of psychiatric disorders.

PMID- 21876509
TI  - Expression of vascular endothelial growth factors VEGF- C and D, VEGFR-3, and
      comparison of lymphatic vessels density labeled with D2-40 antibodies as a
      prognostic factors in vulvar intraepithelial neoplasia (VIN) and invasive vulvar
      cancer.
AB  - OBJECTIVE: The aim of this study was to compare the immunohistochemical
      expression of vascular endothelial growth factors VEGF-C and D, as well as the
      expression of VEGFR-3 in VIN and vulvar invasive cancer and to compare the
      density of lymphatic marker D2-40 antibody in both groups, and to compare them
      with different clinicopathologic features. MATERIALS & METHODS: The study was
      performed using tissue material and clinical data from 100 women diagnosed with
      VIN and 100 women diagnosed with invasive vulvar cancer. RESULTS: No significant
      differences were found in the expression of VEGF-C and -D or VEGFR-3 between
      those patients with VIN and those with invasive vulvar cancers. Weak expression
      of VEGF-C was confirmed only in two cases of the analyzed series; in all cases,
      expression of VEGF-D and VEGFR-3 was observed. The strongest expression of VEGF-D
      and VEGFR-3 was observed in the group of invasive cancers. The highest density of
      lymphatic vessels per 2 mm was observed in VIN. In the cancer group, small
      lymphatic vessels with a narrow oval lumen were observed. Moreover, in two cases
      of vulvar cancer, the presence of intratumoral lymphatic vessels was observed.
      CONCLUSIONS: These results suggest that lymphangiogenesis begins at the
      preinvasive stage of vulvar carcinogenesis and suggests the important role of
      VEGF-C, VEGF-D, VEGFR-3 and LV (D2-40) as prognostic factors in the process of
      carcinogenesis in the vulvar area.

PMID- 21876510
TI  - Ephedrine enhances the antinociceptive effect of dexmedetomidine in mice.
AB  - OBJECTIVES: Dexmedetomidine, a highly selective alpha-2-adrenoceptor agonist, was
      recently introduced into clinical practice for its sedative and analgesic
      properties. The purpose of this study was to evaluate whether the psychostimulant
      drug ephedrine has any effect on dexmedetomidine-induced antinociception and
      locomotor inhibitor activity in mice in acute application. METHODS: In both sexes
      of swiss albino mice; antinociception was assessed with hot-plate test and the
      locomotor, exploratory activities were assessed with holed open field test. The
      animals were received; saline + saline, ephedrine (10 mg/kg) + saline, saline +
      dexmedetomidine (15 MUg/kg) and ephedrine (10 mg/kg) + dexmedetomidine (15
      MUg/kg), intraperitoneally, 30 min before hot plate or holed open field tests.
      RESULTS: In the hot plate test in mice, co-administration of 15 MUg/kg
      dexmedetomidine with 10 mg/kg ephedrine intraperitoneally not only enhanced, but
      also prolonged the duration of antinociception induced by dexmedetomidine. At the
      same time, the locomotor inhibitory effect of dexmedetomidine was counteracted by
      ephedrine. CONCLUSION: We concluded that the combined administration of
      dexmedetomidine with ephedrine may have beneficial effects in the treatment of
      pain without causing sedation, which limits the use of dexmedetomidine as an
      analgesic in humans.

PMID- 21876511
TI  - Electrophysiological evidence of the effect of natural polyphenols upon the human
      higher brain functions.
AB  - OBJECTIVE: Several natural polyphenols exert effects upon the cardiovascular as
      well as nervous system. In vitro and animal studies suggest that polyphenols may
      potentially affect the human cognitive function. The aim was to study the effect
      of ProvinolsTM, the polyphenolic compounds isolated from red wine, upon the human
      higher brain functions. MATERIAL AND METHODS: The accuracy of space memory was
      assessed by means of visually-guided and memory-guided saccadic eye movements.
      The EEG and blood pressure were registered also. The healthy undergraduates
      served as subjects. They were divided into the control, placebo and ProvinolsTM
      groups. The amplitudes of saccades, EEG spectral density, evoked potentials time
      locked to saccadic onset and blood pressure were analyzed in control condition
      and 2 hours later, after administration of placebo, ProvinolsTM (4 mg/kg of body
      weight) or nothing. RESULTS: After the ProvinolsTM administration the memory
      guided saccades were significantly more accurate and the significant decrease in
      the slow EEG bands, alpha power mainly, was registered over the broad regions of
      temporo-parietal cortex. No changes in saccadic eye movement related potentials
      as well as in blood pressure were found after the single dose ProvinolsTM
      administration. CONCLUSIONS: Even a single dose of the ProvinolsTM was able to
      affect positively the space memory for limited time duration. The improvement in
      space memory function and/or the positive role of attentional mechanisms may be
      taken into account mainly. More sensitive analysis of the particular
      participation of attentional and memory components demands the further study.

PMID- 21876512
TI  - Awakening responses and diurnal fluctuations of salivary cortisol, DHEA-S and
      alpha-amylase in healthy male subjects.
AB  - OBJECTIVES: Because the cortisol awakening response (CAR) has received increasing
      attention as a useful index of adrenocortical activity, the primary objective of
      this study was to investigate the presence of an awakening response for various
      salivary biomarkers of adrenocortical activity, including dehydroepiandrosterone
      sulphate (DHEA-S), which acts as a cortisol antagonist, and alpha-amylase, which
      is a predictor of circulating catecholamine activity. Salivary biological
      indicators are considered to be valuable markers of hypothalamus-pituitary
      adrenal (HPA) axis diurnal activity. METHODS: In an attempt to overcome problems
      associated with non-adherence to the requested sampling protocol, only young,
      healthy males with a physiological CAR value (defined as a 50% increase in
      salivary cortisol within 30 min after waking) were included in the study (67 out
      of 102 who initially enrolled met this criterion). RESULTS: Our results suggested
      that, as is already known for cortisol, DHEA-S and alpha-amylase have significant
      awakening responses. In addition, daily profile of salivary cortisol, alpha
      amylase and DHEA-S fluctuations were analysed. Significant correlations were
      found between salivary cortisol, DHEA-S and alpha-amylase levels. The results
      showed that cortisol and DHEA-S concentrations were inversely correlated with
      alpha-amylase levels. CONCLUSION: This correlation confirmed the distinctiveness
      of the two regulatory systems: salivary cortisol and DHEA-S concentrations
      reflect the activity of the HPA axis, whereas alpha-amylase activity is more
      closely related to sympathetic activity. In addition, the present study
      emphasizes the potential value of saliva collection (which is both easy and
      stress-free) in monitoring changes of adrenal function, confirming that multiple
      sampling (especially within 1 h after awakening) is necessary to reliably
      characterise biomarker activity when investigating neuroendocrine changes under
      various conditions.

PMID- 21876513
TI  - Association between perceived happiness levels and peripheral circulating pro
      inflammatory cytokine levels in middle-aged adults in Japan.
AB  - OBJECTIVES: The idea that perceived happiness may be associated with health and
      well-being is a recent topic of focus. However, the neurobiological mechanisms
      underlying the positive effects of happiness on psychological and physiological
      wellness remain obscure. In this study, we attempted to clarify the association
      between systemic inflammation and happiness. METHODS: We recruited 160 healthy
      volunteers for experiment 1 and compared peripheral inflammatory markers, namely
      the concentrations of pro-inflammatory cytokines in the serum, between perceived
      high-happiness and low-happiness groups. Subsequently, we recruited 7 romantic
      couples for experiment 2 and investigated changes in peripheral pro-inflammatory
      cytokine levels after the evocation of happiness, which was induced by warm
      physical contact with the partner. RESULTS: We found that circulating levels of
      interferon-gamma (IFN-gamma), which can affect brain functions and induce
      depressive symptoms, were lower in the high-happiness group than in the low
      happiness group. A negative correlation between the levels of perceived happiness
      and IFN-gamma concentrations was also observed. Furthermore, we also found that
      experimentally induced happiness could reduce peripheral IFN-gamma levels.
      CONCLUSIONS: These results revealed an association between the perception of
      happiness and systemic inflammation. Increased happiness may suppress the
      peripheral circulation of pro-inflammatory cytokines.

PMID- 21876514
TI  - Aspirin resistance and adverse pregnancy outcomes.

PMID- 21876515
TI  - An endovascular treatment of Chronic Cerebro-Spinal Venous Insufficiency in
      multiple sclerosis patients - 6 month follow-up results.
AB  - OBJECTIVE: In this study, the mid-term results (6 month follow-up) of the
      endovascular treatment in patients with Chronic Cerebro-Spinal Venous
      Insufficiency (CCSVI) and multiple sclerosis (MS) were prospectively evaluated.
      METHODS: Thirty-six patients with confirmed MS and CCSVI underwent endovascular
      treatment by the means of the uni- or bilateral jugular vein angioplasty with
      optional stent placement. All the patients completed 6 month follow-up. Their MS
      related disability status and quality of life were evaluated 1, 3 and 6 months
      postoperatively by means of the following scales: Expanded Disability Status
      Scale (EDSS), Multiple Sclerosis Impact Scale (MSIS-29), Epworth Sleepiness Scale
      (ESS), Heat Intolerance scale (HIS) and Fatigue Severity Scale (FSS). For patency
      and restenosis rate assessment, the control US duplex Doppler examination was
      used. RESULTS: Six months after the procedure, restenosis in post-PTA jugular
      veins was found in 33% of cases. Among 17 patients who underwent stent
      implantation into the jugular vein, restenosis or partial in-stent thrombosis was
      identified in 55% of the cases. At the 6 month follow-up appointment, there was
      no significant improvement in the EDSS or the ESS. The endovascular treatment of
      the CCSVI improved the quality of life according to the MSIS-29 scale but only up
      to 3 months after the procedure (with no differences in the 6 month follow-up
      assessment). Six months after the jugular vein angioplasty (with or without stent
      placement), a statistically significant improvement was observed only in the FSS
      and the HIS. CONCLUSIONS: The endovascular treatment in patients with MS and
      concomitant CCSVI did not have an influence on the patient's neurological
      condition; however, in the mid-term follow-up, an improvement in some quality-of
      life parameters was observed.

PMID- 21876516
TI  - Amniopatch - possibility of successful treatment of spontaneous previable rupture
      of membranes in the second trimester of pregnancy by transabdominal intraamiotic
      application of platelets and cryoprecipitate.
AB  - OBJECTIVE: To outline possibility of successful treatment of spontaneous
      previable rupture of membranes in the second trimester of pregnancy.
      INTRODUCTION: Spontaneous previable rupture of membranes (SPROM) in the second
      trimester of pregnancy is one of the most alarming problems in current
      obstetrics. Perinatal mortality is about 60 %, one third of which represents
      intrauterine fetal demise. Surviving neonates suffer from various complications.
      There are different clinical approaches regarding treatment of SPROM. MATERIAL
      AND METHODS: We present a case of a 30 year old secundigravida with a history of
      SPROM at 19+1 weeks gestation. Ultrasonographic examination revealed
      anhydramnios. Genital cultures and laboratory studies ruled out infectious
      etiology of SPROM. Due to expected poor neonatal outcome, decision to attempt
      amniopatch as an experimental therapeutic alternative was made at 21+1 weeks
      gestation (two weeks after SPROM had occurred). Autologous concentrated platelets
      followed by autologous cryoprecipitate were administered into the amniotic cavity
      transabdominally under ultrasound guidance. After 3 days sonographic examination
      showed normal volume of amniotic fluid. On 22 postoperative day, patient notice
      some leaking of fluid vaginally. Fetal growth was appropriate, amniotic fluid
      volume was decreased, however, oligohydramnios never progressed to anhydramnios.
      Pregnancy ended with primary cesarean delivery at 33+1 weeks gestation. Live born
      male infant with 1750 g birth weight was delivered. Postnatal development was
      within normal limits. CONCLUSION: Intraamniotic application of "amniopatch" may
      represent a possibly successful treatment of spontaneous previable rupture of
      membranes. This case reports the longest stop of the leaking of amniotic fluid
      and total prolongation of pregnancy with favorable perinatal outcome after
      "amniopatch" treatment of spontaneous previable rupture of membranes in the
      second trimester so far published in available literature.

PMID- 21876517
TI  - Effect of antipsychotic-induced hyperprolactinemia on anthropometric measures,
      insulin sensitivity and lipid profile in patients with schizophrenia or related
      psychoses.
AB  - OBJECTIVES: This study consisting of two subprojects was undertaken to evaluate
      the effects of hyperprolactinemia on cardiovascular disease (CVD) risk parameters
      such as anthropometric measures, insulin sensitivity and blood lipids in patients
      with schizophrenia or related psychoses on long term treatment with
      antipsychotics. METHODS: In subproject Iota, 45 patients receiving the 2nd
      generation antipsychotics risperidone, clozapine or olanzapine were compared
      regarding prolactin (PRL), body mass index (BMI), insulin, homeostasis model
      assessment of insulin resistance (HOMA-IR) and blood lipids. In subproject Pi, 24
      patients receiving 1st or 2nd generation antipsychotics were investigated with
      diurnal profile of PRL and oral glucose tolerance test (OGTT). RESULTS: Elevated
      PRL levels were found in about 45% of the patients and occurred more often in
      patients receiving risperidone or haloperidol, compared to patients receiving
      clozapine or olanzapine. In contrast, in subproject Iota, insulin and HOMA-IR
      were higher and high density lipoprotein cholesterol was lower in patients
      receiving clozapine or olanzapine, compared with patients receiving risperidone.
      However, PRL levels did not correlate to BMI, insulin, HOMA-IR or lipids in any
      of these three treatment groups. In subproject Pi, OGTT showed impaired glucose
      tolerance in 25% and new-onset diabetes in 4% of the 24 patients investigated.
      Additionally, the PRL (median 24 h) levels correlated positively to the 2 h
      glucose level at OGTT (rs=0.42, p=0.04). CONCLUSIONS: Our findings point to that
      hyperprolactinemia due to 1st and 2nd generation antipsychotics may decrease
      insulin sensitivity, whereas other mechanisms probably underlie insulin
      resistance induced by PRL-sparing antipsychotics such as clozapine and
      olanzapine.

PMID- 21876519
TI  - Preparation of viral DNA from nucleocapsids.
AB  - Viruses are obligate cellular parasites, and thus the study of their DNA requires
      isolating viral material away from host cell contaminants and DNA. Several
      downstream applications require large quantities of pure viral DNA, which is
      provided by this protocol. These applications include viral genome sequencing,
      where the removal of host DNA is crucial to optimize data output for viral
      sequences, and the production of new viral recombinant strains, where co
      transfection of purified plasmid and linear viral DNA facilitates
      recombination.(1,2,3) This procedure utilizes a combination of extractions and
      density-based centrifugation to isolate purified linear herpesvirus nucleocapsid
      DNA from infected cells.(4,5) The initial purification steps aim to isolate
      purified viral capsids, which contain and protect the viral DNA during the
      extractions and centrifugation steps that remove cellular proteins and DNA. Lysis
      of nucleocapsids then releases viral DNA, and two final phenol-chloroform steps
      remove remaining proteins. The final DNA captured from solution is highly
      concentrated and pure, with an average OD(260/280;) of 1.90. Depending on the
      quantity of infected cells used, yields of viral DNA range from 150-800 MUg or
      more. The purity of this DNA makes it stable during long-term storage at 4C. This
      DNA is thus ideally suited for high-throughput sequencing, high fidelity PCR
      reactions, and transfections. Prior to beginning the protocol, it is important to
      know the average number of cells per dish (e.g. an average of 8 x 10(6) PK-15
      cells in a confluent 15 cm dish), and the titer of the viral stock to be used
      (e.g. 1 x 10(8) plaque-forming units per ml). These are necessary to calculate
      the appropriate multiplicity of infection (MOI) for the protocol.(6) For
      instance, to infect one 15 cm dish of PK-15 cells with the above viral stock, at
      an MOI of 5, you would use 400 MUl of viral stock and dilute it with 3.6 ml of
      medium (total inoculation volume of 4 ml for one 15 cm plate). Multiple viral DNA
      preparations can be prepared at the same time. The number of simultaneous
      preparations is limited only by the number of tubes held by the ultracentrifuge
      rotor (one per virus; see step 3.9 below). Here we describe the procedure as
      though being done for one virus.

PMID- 21876518
TI  - Analgesia and endocrine surgical stress: effect of two analgesia protocols on
      cortisol and prolactin levels during abdominal aortic aneurysm endovascular
      repair.
AB  - OBJECTIVES: Endovascular abdominal aortic aneurysm (AAA) repair was performed
      with local anaesthesia and intravenous analgesia. The objective of the study was
      to evaluate how two analgesia protocols affected stress response, measured as
      cortisol, 17-OH progesterone (17OHP) and prolactin (PRL) concentration during the
      procedure. METHODS: 44 patients undergoing elective AAA endovascular repair were
      included to either receive regular boluses of fentanyl midazolam or remifentanil
      continuous infusion, analgesia was monitored by Visual Analogue Scale (VAS)
      measurement; cortisol, 17OHP and PRL were sampled preoperatively, at skin
      incision, endovascular prosthesis release and skin suture. RESULTS: 42 patients
      were included. Mean VAS values were lower in the remifentanil group 0.50+/-0.68
      vs 1.48+/-1.20, p=0.002 at incision, 0.24+/-0.58 vs 1.45+/-1.18, p<0.001
      prosthesis release, 0.51+/-0.90 vs 1.73+/-1.45, p=0.002 suture. No statistically
      significant difference was found among cortisol and 17OHP levels; PRL was
      significantly lower in the fentanyl-midazolam group (23.83+/-16.92 ng/ml vs
      40.81+/-22.45 p=0.009 at prosthesis release and 28.23+/-15.05 vs 41.37+/-14.54,
      p=0.007 at suture). CONCLUSIONS: Although statistically significant VAS
      difference had a limited clinical impact due to its small entity. The group that
      experienced less pain showed a more intense PRL response, while cortisol and
      17OHP did not reach statistical significance.

PMID- 21876520
TI  - Cercarial transformation and in vitro cultivation of Schistosoma mansoni
      schistosomules.
AB  - Schistosome parasites are the causative agents of schistosomiasis, a chronically
      debilitating disease that affects over 200 million people globally and ranks
      second to malaria among parasitic diseases in terms of public health and socio
      economic impact (1-4). Schistosome parasites are trematode worms with a complex
      life cycle interchanging between a parasitic life in molluscan and mammalian
      hosts with intervening free-swimming stages. Briefly, free-swimming cercariae
      infect a mammalian host by penetrating the skin with the aid of secreted
      proteases, during which time the cercariae lose their tails, transforming into
      schistosomules. The schistosomules must now evade the host immune system, develop
      a gut for digestion of red blood cells, and migrate though the lungs and portal
      circulation en route to their final destination in the hepatic portal system and
      eventually the mesenteric veins (for S. mansoni) where male and female worms pair
      and mate, producing hundreds of eggs daily. Some of the eggs are excreted from
      the body into fresh water, where the eggs hatch into free-swimming miracidia (5
      10). The miracidia infect specific snail species and transform into mother and
      daughter sporocysts, which in turn, produce infective cercariae, completing the
      life cycle. Unfortunately, the entire schistosome life cycle cannot be cultured
      in vitro, but infective cercariae can be transformed into schistosomules, and the
      schistosomules can be cultured for weeks for the analysis of schistosome
      development in vitro or microarray analysis. In this protocol, we provide a
      visual description of cercarial transformation and in vitro culturing of
      schistosomules. We shed infectious cercariae from the snail host Biomphalaria
      glabrata and manually transform them into schistosomules by detaching their tails
      using an emulsifying double-ended needle. The in vitro cercarial transformation
      and schistosomules culture techniques described avoid the use of a mammalian
      host, which simplifies visualization of schistosomes and facilitates the
      collection of the parasite for experimental analysis. in vitro transformation and
      culturing techniques of schistosomes have been done for years (11, 12), but no
      visual protocols have been developed that are available to the entire community.

PMID- 21876521
TI  - Cell-based calcium assay for medium to high throughput screening of TRP channel
      functions using FlexStation 3.
AB  - The Molecular Devices' FlexStation 3 is a benchtop multi-mode microplate reader
      capable of automated fluorescence measurement in multi-well plates. It is ideal
      for medium- to high-throughput screens in academic settings. It has an integrated
      fluid transfer module equipped with a multi-channel pipetter and the machine
      reads one column at a time to monitor fluorescence changes of a variety of
      fluorescent reagents. For example, FlexStation 3 has been used to study the
      function of Ca(2+)-permeable ion channels and G-protein coupled receptors by
      measuring the changes of intracellular free Ca(2+) levels. Transient receptor
      potential (TRP) channels are a large family of nonselective cation channels that
      play important roles in many physiological and pathophysiological functions. Most
      of the TRP channels are calcium permeable and induce calcium influx upon
      activation. In this video, we demonstrate the application of FlexStation 3 to
      study the pharmacological profile of the TRPA1 channel, a molecular sensor for
      numerous noxious stimuli. HEK293 cells transiently or stably expressing human
      TRPA1 channels, grown in 96-well plates, are loaded with a Ca(2+)-sensitive
      fluorescent dye, Fluo-4, and real-time fluorescence changes in these cells are
      measured before and during the application of a TRPA1 agonist using the FLEX mode
      of the FlexStation 3. The effect of a putative TRPA1 antagonist was also
      examined. Data are transferred from the SoftMax Pro software to construct
      concentration-response relationships of TRPA1 activators and inhibitors.

PMID- 21876522
TI  - Lensless fluorescent microscopy on a chip.
AB  - On-chip lensless imaging in general aims to replace bulky lens-based optical
      microscopes with simpler and more compact designs, especially for high-throughput
      screening applications. This emerging technology platform has the potential to
      eliminate the need for bulky and/or costly optical components through the help of
      novel theories and digital reconstruction algorithms. Along the same lines, here
      we demonstrate an on-chip fluorescent microscopy modality that can achieve e.g.,
      <4 MUm spatial resolution over an ultra-wide field-of-view (FOV) of >0.6-8 cm(2)
      without the use of any lenses, mechanical-scanning or thin-film based
      interference filters. In this technique, fluorescent excitation is achieved
      through a prism or hemispherical-glass interface illuminated by an incoherent
      source. After interacting with the entire object volume, this excitation light is
      rejected by total-internal-reflection (TIR) process that is occurring at the
      bottom of the sample micro-fluidic chip. The fluorescent emission from the
      excited objects is then collected by a fiber-optic faceplate or a taper and is
      delivered to an optoelectronic sensor array such as a charge-coupled-device
      (CCD). By using a compressive-sampling based decoding algorithm, the acquired
      lensfree raw fluorescent images of the sample can be rapidly processed to yield
      e.g., <4 MUm resolution over an FOV of >0.6-8 cm(2). Moreover, vertically stacked
      micro-channels that are separated by e.g., 50-100 MUm can also be successfully
      imaged using the same lensfree on-chip microscopy platform, which further
      increases the overall throughput of this modality. This compact on-chip
      fluorescent imaging platform, with a rapid compressive decoder behind it, could
      be rather valuable for high-throughput cytometry, rare-cell research and
      microarray-analysis.

PMID- 21876523
TI  - A mouse model of the cornea pocket assay for angiogenesis study.
AB  - A normal cornea is clear of vascular tissues. However, blood vessels can be
      induced to grow and survive in the cornea when potent angiogenic factors are
      administered (1). This uniqueness has made the cornea pocket assay one of the
      most used models for angiogenesis studies. The cornea composes multiple layers of
      cells. It is therefore possible to embed a pellet containing the angiogenic
      factor of interest in the cornea to investigate its angiogenic effect (2,3).
      Here, we provide a step by step demonstration of how to (I) produce the
      angiogenic factor-containing pellet (II) embed the pellet into the cornea (III)
      analyze the angiogenesis induced by the angiogenic factor of interest. Since the
      basic fibroblast growth factor (bFGF) is known as one of the most potent
      angiogenic factors (4), it is used here to induce angiogenesis in the cornea.

PMID- 21876524
TI  - The spared nerve injury (SNI) model of induced mechanical allodynia in mice.
AB  - Peripheral neuropathic pain is a severe chronic pain condition which may result
      from trauma to sensory nerves in the peripheral nervous system. The spared nerve
      injury (SNI) model induces symptoms of neuropathic pain such as mechanical
      allodynia i.e. pain due to tactile stimuli that do not normally provoke a painful
      response [1]. The SNI mouse model involves ligation of two of the three branches
      of the sciatic nerve (the tibial nerve and the common peroneal nerve), while the
      sural nerve is left intact [2]. The lesion results in marked hypersensitivity in
      the lateral area of the paw, which is innervated by the spared sural nerve. The
      non-operated side of the mouse can be used as a control. The advantages of the
      SNI model are the robustness of the response and that it doesn't require expert
      microsurgical skills. The threshold for mechanical pain response is determined by
      testing with von Frey filaments of increasing bending force, which are
      repetitively pressed against the lateral area of the paw [3], [4]. A positive
      pain reaction is defined as sudden paw withdrawal, flinching and/or paw licking
      induced by the filament. A positive response in three out of five repetitive
      stimuli is defined as the pain threshold. As demonstrated in the video protocol,
      C57BL/6 mice experience profound allodynia as early as the day following surgery
      and maintain this for several weeks.

PMID- 21876525
TI  - Single Drosophila ommatidium dissection and imaging.
AB  - The fruit fly Drosophila melanogaster has made invaluable contributions to
      neuroscience research and has been used widely as a model for neurodegenerative
      diseases because of its powerful genetics(1). The fly eye in particular has been
      the organ of choice for neurodegeneration research, being the most accessible and
      life-dispensable part of the Drosophila nervous system. However the major caveat
      of intact eyes is the difficulty, because of the intense autofluorescence of the
      pigment, in imaging intracellular events, such as autophagy dynamics(2), which
      are paramount to understanding of neurodegeneration. We have recently used the
      dissection and culture of single ommatidia(3) that has been essential for our
      understanding of autophagic dysfunctions in a fly model of Dentatorubro
      Pallidoluysian Atrophy (DRPLA)(3, 4). We now report a comprehensive description
      of this technique (Fig. 1), adapted from electrophysiological studies(5), which
      is likely to expand dramatically the possibility of fly models for
      neurodegeneration. This method can be adapted to image live subcellular events
      and to monitor effective drug administration onto photoreceptor cells (Fig. 2).
      If used in combination with mosaic techniques(6-8), the responses of genetically
      different cells can be assayed in parallel (Fig. 2).

PMID- 21876526
TI  - A high throughput in situ hybridization method to characterize mRNA expression
      patterns in the fetal mouse lower urogenital tract.
AB  - Development of the lower urogenital tract (LUT) is an intricate process. This
      complexity is evidenced during formation of the prostate from the fetal male
      urethra, which relies on androgenic signals and epithelial-mesenchymal
      interactions(1,2). Understanding the molecular mechanisms responsible for
      prostate development may reveal growth mechanisms that are inappropriately
      reawakened later in life to give rise to prostate diseases such as benign
      prostatic hyperplasia and prostate cancer. The developing LUT is anatomically
      complex. By the time prostatic budding begins on 16.5 days post conception (dpc),
      numerous cell types are present. Vasculature, nerves and smooth muscle reside
      within the mesenchymal stroma(3). This stroma surrounds a multilayered epithelium
      and gives rise to the fetal prostate through androgen receptor-dependent
      paracrine signals(4). The identity of the stromal androgen receptor-responsive
      genes required for prostate development and the mechanism by which prostate
      ductal epithelium forms in response to these genes is not fully understood. The
      ability to precisely identify cell types and localize expression of specific
      factors within them is imperative to further understand prostate development. In
      situ hybridization (ISH) allows for localization of mRNAs within a tissue. Thus,
      this method can be used to identify pattern and timing of expression of signaling
      molecules and their receptors, thereby elucidating potential prostate
      developmental regulators. Here, we describe a high throughput ISH technique to
      identify mRNA expression patterns in the fetal mouse LUT using vibrating
      microtome-cut sections. This method offers several advantages over other ISH
      protocols. Performing ISH on thin sections adhered to a slide is technically
      difficult; cryosections frequently have poor structural quality while both
      cryosections and paraffin sections often result in weak signal resolution.
      Performing ISH on whole mount tissues can result in probe trapping. In contrast,
      our high throughput technique utilizes thick-cut sections that reveal detailed
      tissue architecture. Modified microfuge tubes allow easy handling of sections
      during the ISH procedure. A maximum of 4 mRNA transcripts can be screened from a
      single 17.5dpc LUT with up to 24 mRNA transcripts detected in a single run,
      thereby reducing cost and maximizing efficiency. This method allows multiple
      treatment groups to be processed identically and as a single unit, thereby
      removing any bias for interpreting data. Most pertinently for prostate
      researchers, this method provides a spatial and temporal location of low and high
      abundance mRNA transcripts in the fetal mouse urethra that gives rise to the
      prostate ductal network.

PMID- 21876527
TI  - Agrobacterium-mediated virus-induced gene silencing assay in cotton.
AB  - Cotton (Gossypium hirsutum) is one of the most important crops worldwide.
      Considerable efforts have been made on molecular breeding of new varieties. The
      large-scale gene functional analysis in cotton has been lagged behind most of the
      modern plant species, likely due to its large size of genome, gene duplication
      and polyploidy, long growth cycle and recalcitrance to genetic transformation(1).
      To facilitate high throughput functional genetic/genomic study in cotton, we
      attempt to develop rapid and efficient transient assays to assess cotton gene
      functions. Virus-Induced Gene Silencing (VIGS) is a powerful technique that was
      developed based on the host Post-Transcriptional Gene Silencing (PTGS) to repress
      viral proliferation(2,3). Agrobacterium-mediated VIGS has been successfully
      applied in a wide range of dicots species such as Solanaceae, Arabidopsis and
      legume species, and monocots species including barley, wheat and maize, for
      various functional genomic studies(3,4). As this rapid and efficient approach
      avoids plant transformation and overcomes functional redundancy, it is
      particularly attractive and suitable for functional genomic study in crop species
      like cotton not amenable for transformation. In this study, we report the
      detailed protocol of Agrobacterium-mediated VIGS system in cotton. Among the
      several viral VIGS vectors, the tobacco rattle virus (TRV) invades a wide range
      of hosts and is able to spread vigorously throughout the entire plant yet produce
      mild symptoms on the hosts5. To monitor the silencing efficiency, GrCLA1, a
      homolog gene of Arabidopsis Cloroplastos alterados 1 gene (AtCLA1) in cotton, has
      been cloned and inserted into the VIGS binary vector pYL156. CLA1 gene is
      involved in chloroplast development(6), and previous studies have shown that loss
      of-function of AtCLA1 resulted in an albino phenotype on true leaves(7),
      providing an excellent visual marker for silencing efficiency. At approximately
      two weeks post Agrobacterium infiltration, the albino phenotype started to appear
      on the true leaves, with 100% silencing efficiency in all replicated experiments.
      The silencing of endogenous gene expression was also confirmed by RT-PCR
      analysis. Significantly, silencing could potently occur in all the cultivars we
      tested, including various commercially grown varieties in Texas. This rapid and
      efficient Agrobacterium-mediated VIGS assay provides a very powerful tool for
      rapid large-scale analysis of gene functions at genome-wide level in cotton.

PMID- 21876528
TI  - Derivation of enriched oligodendrocyte cultures and oligodendrocyte/neuron
      myelinating co-cultures from post-natal murine tissues.
AB  - Identifying the molecular mechanisms underlying OL development is not only
      critical to furthering our knowledge of OL biology, but also has implications for
      understanding the pathogenesis of demyelinating diseases such as Multiple
      Sclerosis (MS). Cellular development is commonly studied with primary cell
      culture models. Primary cell culture facilitates the evaluation of a given cell
      type by providing a controlled environment, free of the extraneous variables that
      are present in vivo. While OL cultures derived from rats have provided a vast
      amount of insight into OL biology, similar efforts at establishing OL cultures
      from mice has been met with major obstacles. Developing methods to culture murine
      primary OLs is imperative in order to take advantage of the available transgenic
      mouse lines. Multiple methods for extraction of OPCs from rodent tissue have been
      described, ranging from neurosphere derivation, differential adhesion
      purification and immunopurification (1-3). While many methods offer success, most
      require extensive culture times and/or costly equipment/reagents. To circumvent
      this, purifying OPCs from murine tissue with an adaptation of the method
      originally described by McCarthy & de Vellis (2) is preferred. This method
      involves physically separating OPCs from a mixed glial culture derived from
      neonatal rodent cortices. The result is a purified OPC population that can be
      differentiated into an OL-enriched culture. This approach is appealing due to its
      relatively short culture time and the unnecessary requirement for growth factors
      or immunopanning antibodies. While exploring the mechanisms of OL development in
      a purified culture is informative, it does not provide the most physiologically
      relevant environment for assessing myelin sheath formation. Co-culturing OLs with
      neurons would lend insight into the molecular underpinnings regulating OL
      mediated myelination of axons. For many OL/neuron co-culture studies, dorsal root
      ganglion neurons (DRGNs) have proven to be the neuron type of choice. They are
      ideal for co-culture with OLs due to their ease of extraction, minimal amount of
      contaminating cells, and formation of dense neurite beds. While studies using
      rat/mouse myelinating xenocultures have been published (4-6), a method for the
      derivation of such OL/DRGN myelinating co-cultures from post-natal murine tissue
      has not been described. Here we present detailed methods on how to effectively
      produce such cultures, along with examples of expected results. These methods are
      useful for addressing questions relevant to OL development/myelinating function,
      and are useful tools in the field of neuroscience.

PMID- 21876529
TI  - Isolating nasal olfactory stem cells from rodents or humans.
AB  - The olfactory mucosa, located in the nasal cavity, is in charge of detecting
      odours. It is also the only nervous tissue that is exposed to the external
      environment and easily accessible in every living individual. As a result, this
      tissue is unique for anyone aiming to identify molecular anomalies in the
      pathological brain or isolate adult stem cells for cell therapy. Molecular
      abnormalities in brain diseases are often studied using nervous tissue samples
      collected post-mortem. However, this material has numerous limitations. In
      contrast, the olfactory mucosa is readily accessible and can be biopsied safely
      without any loss of sense of smell(1). Accordingly, the olfactory mucosa provides
      an "open window" in the adult human through which one can study developmental
      (e.g. autism, schizophrenia)(2-4) or neurodegenerative (e.g. Parkinson,
      Alzheimer) diseases(4,5). Olfactory mucosa can be used for either comparative
      molecular studies(4,6) or in vitro experiments on neurogenesis(3,7). The
      olfactory epithelium is also a nervous tissue that produces new neurons every day
      to replace those that are damaged by pollution, bacterial of viral infections.
      This permanent neurogenesis is sustained by progenitors but also stem cells
      residing within both compartments of the mucosa, namely the neuroepithelium and
      the underlying lamina propria(8-10). We recently developed a method to purify the
      adult stem cells located in the lamina propria and, after having demonstrated
      that they are closely related to bone marrow mesenchymal stem cells (BM-MSC), we
      named them olfactory ecto-mesenchymal stem cells (OE-MSC)(11). Interestingly,
      when compared to BM-MSCs, OE-MSCs display a high proliferation rate, an elevated
      clonogenicity and an inclination to differentiate into neural cells. We took
      advantage of these characteristics to perform studies dedicated to unveil new
      candidate genes in schizophrenia and Parkinson's disease(4). We and others have
      also shown that OE-MSCs are promising candidates for cell therapy, after a spinal
      cord trauma(12,13), a cochlear damage(14) or in an animal models of Parkinson's
      disease(15) or amnesia(16). In this study, we present methods to biopsy olfactory
      mucosa in rats and humans. After collection, the lamina propria is enzymatically
      separated from the epithelium and stem cells are purified using an enzymatic or a
      non-enzymatic method. Purified olfactory stem cells can then be either grown in
      large numbers and banked in liquid nitrogen or induced to form spheres or
      differentiated into neural cells. These stem cells can also be used for
      comparative omics (genomic, transcriptomic, epigenomic, proteomic) studies.

PMID- 21876530
TI  - Lateral fluid percussion: model of traumatic brain injury in mice.
AB  - Traumatic brain injury (TBI) research has attained renewed momentum due to the
      increasing awareness of head injuries, which result in morbidity and mortality.
      Based on the nature of primary injury following TBI, complex and heterogeneous
      secondary consequences result, which are followed by regenerative processes
      (1,2). Primary injury can be induced by a direct contusion to the brain from
      skull fracture or from shearing and stretching of tissue causing displacement of
      brain due to movement (3,4). The resulting hematomas and lacerations cause a
      vascular response (3,5), and the morphological and functional damage of the white
      matter leads to diffuse axonal injury (6-8). Additional secondary changes
      commonly seen in the brain are edema and increased intracranial pressure (9).
      Following TBI there are microscopic alterations in biochemical and physiological
      pathways involving the release of excitotoxic neurotransmitters, immune mediators
      and oxygen radicals (10-12), which ultimately result in long-term neurological
      disabilities (13,14). Thus choosing appropriate animal models of TBI that present
      similar cellular and molecular events in human and rodent TBI is critical for
      studying the mechanisms underlying injury and repair. Various experimental models
      of TBI have been developed to reproduce aspects of TBI observed in humans, among
      them three specific models are widely adapted for rodents: fluid percussion,
      cortical impact and weight drop/impact acceleration (1). The fluid percussion
      device produces an injury through a craniectomy by applying a brief fluid
      pressure pulse on to the intact dura. The pulse is created by a pendulum striking
      the piston of a reservoir of fluid. The percussion produces brief displacement
      and deformation of neural tissue (1,15). Conversely, cortical impact injury
      delivers mechanical energy to the intact dura via a rigid impactor under
      pneumatic pressure (16,17). The weight drop/impact model is characterized by the
      fall of a rod with a specific mass on the closed skull (18). Among the TBI
      models, LFP is the most established and commonly used model to evaluate mixed
      focal and diffuse brain injury (19). It is reproducible and is standardized to
      allow for the manipulation of injury parameters. LFP recapitulates injuries
      observed in humans, thus rendering it clinically relevant, and allows for
      exploration of novel therapeutics for clinical translation (20). We describe the
      detailed protocol to perform LFP procedure in mice. The injury inflicted is mild
      to moderate, with brain regions such as cortex, hippocampus and corpus callosum
      being most vulnerable. Hippocampal and motor learning tasks are explored
      following LFP.

PMID- 21876531
TI  - Imaging leukocyte adhesion to the vascular endothelium at high intraluminal
      pressure.
AB  - Worldwide, hypertension is reported to be in approximately a quarter of the
      population and is the leading biomedical risk factor for mortality worldwide. In
      the vasculature hypertension is associated with endothelial dysfunction and
      increased inflammation leading to atherosclerosis and various disease states such
      as chronic kidney disease(2), stroke(3) and heart failure(4). An initial step in
      vascular inflammation leading to atherogenesis is the adhesion cascade which
      involves the rolling, tethering, adherence and subsequent transmigration of
      leukocytes through the endothelium. Recruitment and accumulation of leukocytes to
      the endothelium is mediated by an upregulation of adhesion molecules such as
      vascular cell adhesion molecule-1 (VCAM-1), intracellular cell adhesion molecule
      1 (ICAM-1) and E-selectin as well as increases in cytokine and chemokine release
      and an upregulation of reactive oxygen species(5). In vitro methods such as
      static adhesion assays help to determine mechanisms involved in cell-to-cell
      adhesion as well as the analysis of cell adhesion molecules. Methods employed in
      previous in vitro studies have demonstrated that acute increases in pressure on
      the endothelium can lead to monocyte adhesion, an upregulation of adhesion
      molecules and inflammatory markers(6) however, similar to many in vitro assays,
      these findings have not been performed in real time under physiological flow
      conditions, nor with whole blood. Therefore, in vivo assays are increasingly
      utilised in animal models to demonstrate vascular inflammation and plaque
      development. Intravital microscopy is now widely used to assess leukocyte
      adhesion, rolling, migration and transmigration(7-9). When combining the effects
      of pressure on leukocyte to endothelial adhesion the in vivo studies are less
      extensive. One such study examines the real time effects of flow and shear on
      arterial growth and remodelling but inflammatory markers were only assessed via
      immunohistochemistry(10). Here we present a model for recording leukocyte
      adhesion in real time in intact pressurised blood vessels using whole blood
      perfusion. The methodology is a modification of an ex vivo vessel chamber
      perfusion model(9) which enables real-time analysis of leukocyte-endothelial
      adhesive interactions in intact vessels. Our modification enables the
      manipulation of the intraluminal pressure up to 200 mmHg allowing for study not
      only under physiological flow conditions but also pressure conditions. While
      pressure myography systems have been previously demonstrated to observe vessel
      wall and lumen diameter(11) as well as vessel contraction this is the first time
      demonstrating leukocyte-endothelial interactions in real time. Here we
      demonstrate the technique using carotid arteries harvested from rats and
      cannulated to a custom-made flow chamber coupled to a fluorescent microscope. The
      vessel chamber is equipped with a large bottom coverglass allowing a large
      diameter objective lens with short working distance to image the vessel.
      Furthermore, selected agonist and/or antagonists can be utilized to further
      investigate the mechanisms controlling cell adhesion. Advantages of this method
      over intravital microscopy include no involvement of invasive surgery and
      therefore a higher throughput can be obtained. This method also enables the use
      of localised inhibitor treatment to the desired vessel whereas intravital only
      enables systemic inhibitor treatment.

PMID- 21876532
TI  - Design of a cyclic pressure bioreactor for the ex vivo study of aortic heart
      valves.
AB  - The aortic valve, located between the left ventricle and the aorta, allows for
      unidirectional blood flow, preventing backflow into the ventricle. Aortic valve
      leaflets are composed of interstitial cells suspended within an extracellular
      matrix (ECM) and are lined with an endothelial cell monolayer. The valve
      withstands a harsh, dynamic environment and is constantly exposed to shear,
      flexion, tension, and compression. Research has shown calcific lesions in
      diseased valves occur in areas of high mechanical stress as a result of
      endothelial disruption or interstitial matrix damage(1-3). Hence, it is not
      surprising that epidemiological studies have shown high blood pressure to be a
      leading risk factor in the onset of aortic valve disease(4). The only treatment
      option currently available for valve disease is surgical replacement of the
      diseased valve with a bioprosthetic or mechanical valve(5). Improved
      understanding of valve biology in response to physical stresses would help
      elucidate the mechanisms of valve pathogenesis. In turn, this could help in the
      development of non-invasive therapies such as pharmaceutical intervention or
      prevention. Several bioreactors have been previously developed to study the
      mechanobiology of native or engineered heart valves(6-9). Pulsatile bioreactors
      have also been developed to study a range of tissues including cartilage(10),
      bone(11) and bladder(12). The aim of this work was to develop a cyclic pressure
      system that could be used to elucidate the biological response of aortic valve
      leaflets to increased pressure loads. The system consisted of an acrylic chamber
      in which to place samples and produce cyclic pressure, viton diaphragm solenoid
      valves to control the timing of the pressure cycle, and a computer to control
      electrical devices. The pressure was monitored using a pressure transducer, and
      the signal was conditioned using a load cell conditioner. A LabVIEW program
      regulated the pressure using an analog device to pump compressed air into the
      system at the appropriate rate. The system mimicked the dynamic transvalvular
      pressure levels associated with the aortic valve; a saw tooth wave produced a
      gradual increase in pressure, typical of the transvalvular pressure gradient that
      is present across the valve during diastole, followed by a sharp pressure drop
      depicting valve opening in systole. The LabVIEW program allowed users to control
      the magnitude and frequency of cyclic pressure. The system was able to subject
      tissue samples to physiological and pathological pressure conditions. This device
      can be used to increase our understanding of how heart valves respond to changes
      in the local mechanical environment.

PMID- 21876533
TI  - Autologous blood injection to model spontaneous intracerebral hemorrhage in mice.
AB  - Investigation of the pathophysiology of injury after intracerebral hemorrhage
      (ICH) requires a reproducible animal model. While ICH accounts for 10-15% of all
      strokes, there remains no specific effective therapy. The autologous blood
      injection model in mice involves the stereotaxic injection of arterial blood into
      the basal ganglia mimicking a spontaneous hypertensive hemorrhage in man. The
      response to hemorrhage can then be studied in vivo and the neurobehavioral
      deficits quantified, allowing for description of the ensuing pathology and the
      testing of potential therapeutic agents. The procedure described in this protocol
      uses the double injection technique to minimize risk of blood reflux up the
      needle track, no anticoagulants in the pumping system, and eliminates all dead
      space and expandable tubing in the system.

PMID- 21876534
TI  - Combined loss of p21(waf1/cip1) and p27(kip1) enhances tumorigenesis in mice.
AB  - The cell cycle inhibitors p21(Waf1/Cip1) and p27(Kip1) are frequently
      downregulated in many human cancers, and correlate with a worse prognosis. We
      show here that combined deficiency in p21 and p27 proteins in mice is linked to
      more aggressive spontaneous tumorigenesis, resulting in a decreased lifespan. The
      most common tumors developed in p21p27 double-null mice were endocrine, with a
      higher incidence of pituitary adenomas, pheochromocytomas and thyroid adenomas.
      The combined absence of p21 and p27 proteins delays the incidence of radiation
      induced thymic lymphomas with a higher apoptotic rate, measured by active caspase
      3 and cleaved PARP-1 immunoexpresion. These results provide experimental evidence
      for a cooperation of both cyclin-dependent kinase inhibitors in tumorigenesis in
      mice.

PMID- 21876535
TI  - TGF-beta signaling in endothelial cells, but not neuroepithelial cells, is
      essential for cerebral vascular development.
AB  - The various organs of the body harbor blood vessel networks that display unique
      structural and functional features; however, the mechanisms that control organ
      specific vascular development and physiology remain mostly unknown. In the
      developing mouse brain, alphavbeta8 integrin-mediated TGF-beta activation and
      signaling is essential for normal blood vessel growth and sprouting. Whether
      integrins activate TGF-beta signaling pathways in vascular endothelial cells
      (ECs), neural cells, or both, has yet to be determined. Here, we have generated
      and characterized mice in which TGF-beta receptors are specifically deleted in
      neuroepithelial cells via Nestin-Cre, or in ECs via a novel Cre transgenic strain
      (Alk1(GFPCre)) in which Cre is expressed under control of the endogenous activin
      receptor-like kinase 1 (Alk1) promoter. We report that deletion of Tgfbr2 in the
      neuroepithelium does not impact brain vascular development. In contrast,
      selective deletion of the Tgfbr2 or Alk5 genes in ECs result in embryonic
      lethality because of brain-specific vascular pathologies, including blood vessel
      morphogenesis and intracerebral hemorrhage. These data reveal for the first time
      that alphavbeta8 integrin-activated TGF-betas regulate angiogenesis in the
      developing brain via paracrine signaling to ECs.

PMID- 21876536
TI  - Netrin-1 overexpression in kidney proximal tubular epithelium ameliorates
      cisplatin nephrotoxicity.
AB  - Netrin-1, a multifunctional laminin-related protein is widely expressed in
      various tissues, including kidney. The pathophysiological roles of netrin-1 in
      toxic acute kidney injury are unknown. To determine the role of netrin-1 in
      cisplatin-induced nephrotoxicity, we used netrin-1 transgenic mice that
      overexpress netrin-1 in the proximal tubular epithelium using the fatty acid
      binding protein promoter. Administration of cisplatin caused severe renal injury
      in WT mice but not in netrin-1 transgenic mice. Functional improvement was
      associated with better preservation of morphology, reduced cytokine expression
      and oxidative stress in the kidney, and reduced serum and urine cytokine and
      chemokine levels of transgenic mice as compared with WT mice. Cisplatin induced
      an increase in neutrophil infiltration into the kidney of WT mice, which was not
      significantly reduced in netrin-1 transgenic mice. Interestingly, ischemia
      reperfusion induced a large increase in apoptosis in WT mice but not in netrin-1
      transgenic mice (215 +/- 40 vs 94 +/- 20 cells/5 HPF ( * 400), P < 0.0001), which
      was associated with reduced caspase-3 and p53 activation in the transgenic
      kidney. These results suggest that netrin-1 protects renal tubular epithelial
      cells against cisplatin-induced kidney injury by suppressing apoptosis and
      inflammation.

PMID- 21876537
TI  - Dimethyloxalyglycine stimulates the early stages of gastrointestinal repair
      processes through VEGF-dependent mechanisms.
AB  - Dimethyloxalylglycine (DMOG) is an inhibitor of prolyl-4-hydroxylase domain
      enzymes. Its potential value and mechanism of actions in preventing/treating
      gastrointestinal injury are, however, poorly understood. We, therefore, examined
      the effect of DMOG on influencing gut injury and repair using a variety of in
      vitro and in vivo models. We performed in vitro studies utilising pro-migratory
      (wounded monolayer) and proliferation (using DNA quantitation) assays of human
      stomach (AGS) and colonic (HT29) carcinoma cells. Time course studies examined
      changes in hypoxia-inducible factor (HIF) and vascular endothelial growth factor
      (VEGF) levels, a growth factor known to be regulated via HIF. In vivo studies
      utilised a rat gastric (indomethacin, 20 mg/kg and 3 h restraint) damage model.
      DMOG stimulated migration in a dose-dependent manner, increasing migration
      twofold when added at 25MUM (P<0.01). Additive effects were seen when DMOG was
      added to cells in hypoxic conditions. DMOG stimulated proliferation dose
      dependently, increasing proliferation threefold when added at 70 MUM (P<0.01).
      DMOG caused upregulation of both HIF and VEGF within 4 h of administration.
      Addition of VEGF neutralising antibody truncated migratory and proliferative
      activity of DMOG by about 70%. Both oral and subcutaneous administration of DMOG
      decreased gastric injury without influencing intragastric pH (50% reduction in
      injury when 1 ml gavaged at 0.57 mM, P < 0.01). Indomethacin reduced tissue HIF
      and VEGF levels but this was prevented if DMOG was present. In conclusion, DMOG
      stimulates the early phases of gut repair and VEGF-dependent processes appear
      relevant. Non-peptide factors such as this may be useful to stabilise or repair
      gut mucosa.

PMID- 21876538
TI  - mTORC1 activation triggers the unfolded protein response in podocytes and leads
      to nephrotic syndrome.
AB  - Although podocyte damage is known to be responsible for the development of
      minimal-change disease (MCD), the underlying mechanism remains to be elucidated.
      Previously, using a rat MCD model, we showed that endoplasmic reticulum (ER)
      stress in the podocytes was associated with the heavy proteinuric state and
      another group reported that a mammalian target of rapamycin complex 1 (mTORC1)
      inhibitor protected against proteinuria. In this study, which utilized a rat MCD
      model, a combination of immunohistochemistry, dual immunofluorescence and
      confocal microscopy, western blot analysis, and quantitative real-time RT-PCR
      revealed co-activation of the unfolded protein response (UPR), which was induced
      by ER stress, and mTORC1 in glomerular podocytes before the onset of proteinuria
      and downregulation of nephrin at the post-translational level at the onset of
      proteinuria. Podocyte culture experiments revealed that mTORC1 activation
      preceded the UPR that was associated with a marked decrease in the energy charge.
      The mTORC1 inhibitor everolimus completely inhibited proteinuria through a
      reduction in both mTORC1 and UPR activity and preserved nephrin expression in the
      glomerular podocytes. In conclusion, mTORC1 activation may perturb the regulatory
      system of energy metabolism primarily by promoting energy consumption and
      inducing the UPR, which underlie proteinuria in MCD.

PMID- 21876541
TI  - ZNF804A and social cognition in patients with schizophrenia and healthy controls.

PMID- 21876540
TI  - Statistical epistasis and progressive brain change in schizophrenia: an approach
      for examining the relationships between multiple genes.
AB  - Although schizophrenia is generally considered to occur as a consequence of
      multiple genes that interact with one another, very few methods have been
      developed to model epistasis. Phenotype definition has also been a major
      challenge for research on the genetics of schizophrenia. In this report, we use
      novel statistical techniques to address the high dimensionality of genomic data,
      and we apply a refinement in phenotype definition by basing it on the occurrence
      of brain changes during the early course of the illness, as measured by repeated
      magnetic resonance scans (i.e., an 'intermediate phenotype.') The method combines
      a machine-learning algorithm, the ensemble method using stochastic gradient
      boosting, with traditional general linear model statistics. We began with 14
      genes that are relevant to schizophrenia, based on association studies or their
      role in neurodevelopment, and then used statistical techniques to reduce them to
      five genes and 17 single nucleotide polymorphisms (SNPs) that had a significant
      statistical interaction: five for PDE4B, four for RELN, four for ERBB4, three for
      DISC1 and one for NRG1. Five of the SNPs involved in these interactions replicate
      previous research in that, these five SNPs have previously been identified as
      schizophrenia vulnerability markers or implicate cognitive processes relevant to
      schizophrenia. This ability to replicate previous work suggests that our method
      has potential for detecting a meaningful epistatic relationship among the genes
      that influence brain abnormalities in schizophrenia.

PMID- 21876542
TI  - The neural consequences of combat stress: long-term follow-up.

PMID- 21876539
TI  - Genome-wide association analysis of coffee drinking suggests association with
      CYP1A1/CYP1A2 and NRCAM.
AB  - Coffee consumption is a model for addictive behavior. We performed a meta
      analysis of genome-wide association studies (GWASs) on coffee intake from 8
      Caucasian cohorts (N=18 176) and sought replication of our top findings in a
      further 7929 individuals. We also performed a gene expression analysis treating
      different cell lines with caffeine. Genome-wide significant association was
      observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The
      two SNPs rs2470893 and rs2472297 (P-values=1.6 * 10(-11) and 2.7 * 10(-11)),
      which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie
      in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2
      genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated
      with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons,
      which are important constituents of coffee, whereas CYP1A2 is involved in the
      primary metabolism of caffeine. Significant evidence of association was also
      detected at rs382140 (P-value=3.9 * 10(-09)) near NRCAM-a gene implicated in
      vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1
      * 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the
      gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results
      from GWASs and expression analysis also strongly implicate CAB39L in coffee
      drinking. Pathway analysis of differentially expressed genes revealed
      significantly enriched ubiquitin proteasome (P-value=2.2 * 10(-05)) and
      Parkinson's disease pathways (P-value=3.6 * 10(-05)).

PMID- 21876544
TI  - Converging evidence for central 5-HT effects in acute tryptophan depletion.

PMID- 21876545
TI  - Dopamine transporter genotype predicts behavioural and neural measures of
      response inhibition.
AB  - The ability to inhibit unwanted actions is a heritable executive function that
      may confer risk to disorders such as attention deficit hyperactivity disorder
      (ADHD). Converging evidence from pharmacology and cognitive neuroscience suggests
      that response inhibition is instantiated within frontostriatal circuits of the
      brain with patterns of activity that are modulated by the catecholamines dopamine
      and noradrenaline. A total of 405 healthy adult participants performed the stop
      signal task, a paradigmatic measure of response inhibition that yields an index
      of the latency of inhibition, termed the stop-signal reaction time (SSRT). Using
      this phenotype, we tested for genetic association, performing high-density single
      nucleotide polymorphism mapping across the full range of autosomal catecholamine
      genes. Fifty participants also underwent functional magnetic resonance imaging to
      establish the impact of associated alleles on brain and behaviour. Allelic
      variation in polymorphisms of the dopamine transporter gene (SLC6A3: rs37020;
      rs460000) predicted individual differences in SSRT, after corrections for
      multiple comparisons. Furthermore, activity in frontal regions (anterior frontal,
      superior frontal and superior medial gyri) and caudate varied additively with the
      T-allele of rs37020. The influence of genetic variation in SLC6A3 on the
      development of frontostriatal inhibition networks may represent a key risk
      mechanism for disorders of behavioural inhibition.

PMID- 21876543
TI  - An aetiological Foxp2 mutation causes aberrant striatal activity and alters
      plasticity during skill learning.
AB  - Mutations in the human FOXP2 gene cause impaired speech development and
      linguistic deficits, which have been best characterised in a large pedigree
      called the KE family. The encoded protein is highly conserved in many vertebrates
      and is expressed in homologous brain regions required for sensorimotor
      integration and motor-skill learning, in particular corticostriatal circuits.
      Independent studies in multiple species suggest that the striatum is a key site
      of FOXP2 action. Here, we used in vivo recordings in awake-behaving mice to
      investigate the effects of the KE-family mutation on the function of striatal
      circuits during motor-skill learning. We uncovered abnormally high ongoing
      striatal activity in mice carrying an identical mutation to that of the KE
      family. Furthermore, there were dramatic alterations in striatal plasticity
      during the acquisition of a motor skill, with most neurons in mutants showing
      negative modulation of firing rate, starkly contrasting with the predominantly
      positive modulation seen in control animals. We also observed striking changes in
      the temporal coordination of striatal firing during motor-skill learning in
      mutants. Our results indicate that FOXP2 is critical for the function of striatal
      circuits in vivo, which are important not only for speech but also for other
      striatal-dependent skills.

PMID- 21876547
TI  - Cholesterol efflux from macrophages is influenced differentially by plasmas from
      overweight insulin-sensitive and -resistant subjects.
AB  - OBJECTIVE: In vitro measurements of cholesterol efflux from macrophages have
      recently been shown to associate with cardiovascular risk. We investigated
      whether cholesterol efflux from macrophages incubated with plasmas from
      overweight/obese subjects with metabolic syndrome was influenced by the presence
      of insulin resistance. METHODS: Plasmas were obtained from 47 men and women with
      metabolic syndrome, of whom 25 were found to be insulin resistant (IR) and 22
      insulin sensitive (IS) (Matsuda, De Fronzo equation based on oral glucose
      tolerance test). Activated human macrophage THP-1 cells in which cholesterol had
      been radiolabelled were incubated with the subjects' plasmas to allow calculation
      of % cholesterol efflux. RESULTS: Body mass index and waist measurements, as well
      as plasma lipid levels, did not differ between the two groups. Homeostatic model
      assessment-insulin resistance value as well as plasma insulin and leptin
      concentrations were higher in IR subjects. Cholesterol efflux was found to be
      significantly greater with plasmas from IR subjects (9.1%) than from IS subjects
      (6.7%) (P=0.005). Further, cholesterol efflux was significantly inversely
      associated with insulin sensitivity index (P<0.001), directly with arterial
      insulin concentration (P<0.001) and directly with cholesteryl ester transfer
      protein (CETP) mass (P=0.044). CONCLUSION: Plasmas from overweight subjects with
      insulin resistance induced greater in vitro cholesterol efflux compared with IS
      subjects. Efflux inversely correlated with insulin sensitivity suggesting an
      increase in reverse cholesterol transport in the IR state that may lead to
      greater transfer of cholesterol to apoB lipoproteins from high-density
      lipoproteins via CETP as a factor in the association between IR and
      atherosclerosis.

PMID- 21876546
TI  - Incidence and prevalence of copper deficiency following roux-en-y gastric bypass
      surgery.
AB  - INTRODUCTION AND OBJECTIVES: The frequency of copper deficiency and clinical
      manifestations following roux-en-y gastric bypass (RYGB) surgery is not yet
      clear. Objectives were to determine the prevalence and incidence of copper
      deficiency in patients who have undergone RYGB. DESIGN AND METHODS: We sought to
      determine the number of RYGB patients undergoing medical and nutritional follow
      up visits at the Emory Bariatric Center who experienced copper deficiency and
      associated hematological and neurological complaints (n=136). Separately, in
      patients followed longitudinally before and during 6 and 24 months following RYGB
      surgery, we obtained measures of copper status (n=16). Systemic blood cell counts
      and measures of copper, zinc and ceruloplasmin were determined using standardized
      assays in reference laboratories including atomic absorption spectrometry and
      immunoassays. RESULTS: Thirteen patients were identified to have copper
      deficiency suggesting a prevalence of copper deficiency of 9.6%, and the majority
      of these had concomitant complications including anemia, leukopenia and various
      neuro-muscular abnormalities. In the longitudinal study, plasma copper
      concentrations and ceruloplasmin activity decreased over 6 and 24 months
      following surgery, respectively (P<0.05), but plasma zinc concentrations did not
      change. A simultaneous decrease in white blood cells was observed (P<0.05). The
      incidence of copper deficiency in these subjects was determined to be 18.8%.
      CONCLUSIONS: The prevalence and incidence of copper deficiency following RYGB
      surgery was determined to be 9.6% and 18.8%, respectively, with many patients
      experiencing mild-to-moderate symptoms. Given that copper deficiency can lead to
      serious and irreversible complications if untreated, frequent monitoring of the
      copper status of RYGB patients is warranted.

PMID- 21876548
TI  - Regulation of LKB1 expression by sex hormones in adipocytes.
AB  - OBJECTIVE: In the adipose tissue, activation of AMP-activated protein kinase
      (AMPK) by phosphorylation favours local fatty acid oxidation and inhibition of
      lipogenesis. We have previously shown that the potent androgen
      dihydrotestosterone (DHT) can inhibit phosphorylation of AMPK in adipose tissue
      and 3T3-L1 adipocytes in a dose-dependent manner. This negative effect of DHT was
      reversed by oestrogen treatment. The purpose of this current study was to
      determine the underlying mechanisms whereby androgens and oestrogens can regulate
      AMPK phosphorylation in adipocytes, and whether this mechanism is receptor
      dependent. RESULTS: Phosphorylation of AMPK was assessed by western blot in cells
      treated for 24 h with testosterone or DHT (1-1000 nM). Testosterone and DHT
      significantly inhibited basal phosphorylation of AMPK. Addition of the androgen
      receptor antagonist Flutamide (1 MUM) to the media reversed the negative effect
      of testosterone and DHT by returning AMPK phosphorylation levels to those of
      basal. To further dissect the mechanism underlying AMPK inhibition by
      testosterone or DHT, we examined the mRNA expression of the upstream activator of
      AMPK, namely LKB1. Testosterone and DHT treatment of murine 3T3-L1 or human SGBS
      adipocytes for 24 h significantly decreased the mRNA expression of LKB1. In
      contrast, 17beta-estradiol treatment increased LKB1 mRNA, an effect mediated by
      oestrogen receptor alpha. CONCLUSION: We conclude that regulation of AMPK
      phosphorylation by androgens and oestrogens is receptor-dependent, and
      demonstrate for the first time that LKB1 is regulated by sex hormones in
      adipocytes.

PMID- 21876549
TI  - SmartPill technology provides safe and effective assessment of gastrointestinal
      function in persons with spinal cord injury.
AB  - STUDY DESIGN: Spinal cord injury (SCI) results in gastrointestinal (GI)
      complications, including gastroesophageal reflux disease and constipation, but
      much of the data is based on older technology. OBJECTIVE: GI transit times were
      determined in subjects with SCI using a new device called a SmartPill. Our
      principal goal was to assess whether this new technology can be applied in
      persons with SCI. METHODS: SCI and age- and gender-matched able-bodied (AB)
      control subjects not taking proton pump inhibitors were studied. Following an 8-h
      overnight fast, subjects consumed 120 g EggBeaters (60 kcal), two slices of white
      bread (120 kcal) and 30 g strawberry jam (74 kcal). A pH calibrated SmartPill
      capsule was swallowed with 8 ounces of water, after which subjects fasted for an
      additional 6 h prior to consuming an Ensure Plus nutrition shake (350 kcal).
      Subjects remained fasted for an additional 2 h, after which time they resumed
      their regular diets. RESULTS: Twenty subjects with SCI and 10 AB control subjects
      were studied. Data are expressed as mean+/-s.d. Comparing the group with SCI to
      the AB control group, gastric emptying time (GET), colonic transit time (CTT) and
      whole gut transit time (WGTT) were prolonged (GET: 10.6+/-7.2 vs 3.5+/-1.0 h,
      P<0.01; CTT: 52.3+/-42.9 vs 14.2+/-7.6 h, P=0.01; WGTT: 3.3+/-2.5 vs 1.0+/-0.7
      days, P<0.01). No complications or side effects were reported. CONCLUSION: Our
      results indicate that the SmartPill technology is a safe, non-invasive assessment
      technique that provides valid diagnostic information in persons with SCI.

PMID- 21876550
TI  - Quality of life and urological morbidity in tetraplegics with artificial
      ventilation managed with suprapubic or intermittent catheterisation.
AB  - STUDY DESIGN: Mono-centric, retrospective study. OBJECTIVE: Analysis of
      correlation between bladder management and age in respirator-dependant high
      tetraplegic patients. Additionally suprapubic catheter (SPC) and intermittent
      catheterisation (IC) were reviewed concerning urological complications and
      quality of life (QoL). SETTING: Level 1 trauma centre. METHODS: A QoL
      questionnaire 'International Consultation on Incontinence' (ICIQ-SF) was sent to
      56 tetraplegic respirator device-dependant (RDD)-spinal cord injury (SCI)
      patients. Their scores concerning urological morbidity were reviewed. For
      analysis reasons they were divided in three groups: SPC, IC and others. RESULTS:
      SPC 38, IC 12 and others 6 patients. Significant difference in age (SPC vs
      IC=49.9 vs 31.8 years) was observed but no disparity in gender. Within a follow
      up period 2-26 years (median 8 years) significant urological complications in
      patients with IC (P<0.05) were ascertained. These were in general minor
      complications. Especially renal deterioration or bladder cancer was not diagnosed
      in any of the group. The questionnaire return rate was high (83.9%) with complete
      answers (SPC=32, IC=11). Self assessment of QoL with ICIQ-SF revealed no
      significant difference for both groups on low level, but SPC patients tend to
      score better. CONCLUSION: In our study, tetraplegic RDD-SCI patients with SPC
      suffered less urological complications and tend to score a better QoL. Therefore
      we recommend SPC as a serious alternative for these selected patients and
      concurrently underline the necessity of close urological surveillance at least
      annually.

PMID- 21876551
TI  - Relationship between function, strength and electromyography of upper extremities
      of persons with tetraplegia.
AB  - STUDY DESIGN: Cross-sectional. OBJECTIVE: To analyze the relationships between
      functional tests, arm strength and root mean square of surface electromyography
      (EMG). SETTING: Sao Paulo, Brazil. METHODS: Twenty-four individuals with chronic
      tetraplegia participated. Upper extremity motor score (UEMS), functional
      independence measure (FIM) motor score, spinal cord independence measure III and
      capabilities of upper extremity (CUE) were performed. Muscle strength of the
      right elbow flexors-extensors was assessed using dynamometry and manual muscle
      test (MMT) and EMG of right biceps and triceps brachii were performed. Spearman's
      rank correlation coefficients and Mann-Whitney's U-test were used. RESULTS:
      Functional tests and UEMS correlated strongly among them. UEMS highly correlated
      with triceps dynamometry and EMG. The dynamometry showed a very high correlation
      with MMT on the extensor group and a moderate correlation with flexor group.
      Triceps EMG showed moderate correlation with FIM and CUE. High correlations
      between triceps EMG and elbow extensors dynamometry and MMT were observed. A
      significant better performance on functional tests was observed on lower ASIA
      motor levels. The low-tetraplegia group showed a significant higher score on
      triceps EMG and dynamometry. CONCLUSION: Arm strength and EMG seem to be related
      to functional capabilities and independence in chronic tetraplegia.

PMID- 21876552
TI  - Effect of age on bowel management in traumatic central cord syndrome.
AB  - STUDY DESIGN: A retrospective multicenter study. OBJECTIVES: To investigate the
      characteristics of bowel dysfunction in elderly people with traumatic central
      cord syndrome (TCCS). SETTING: A total of 28 Rosai hospitals in Japan. METHODS:
      The Rosai Hospital registry included 3006 persons with spinal cord injury during
      1997-2007. The study subjects were 186 patients with TCCS (160 men, 26 women;
      mean age, 61.7+/-11.6 years, +/-s.d.). Patients were divided according to age
      into the young group (<50 years, n=30), the middle-age group (50-69 years, n=112)
      and the elderly group (>=70 years, n=44). We assessed the differences in bowel
      management techniques (spontaneous, rectal medications and manual emptying) and
      activity of daily living (ADL) with respect to bowel care at discharge among the
      three groups. RESULTS: Continent spontaneous defecation was the most common bowel
      management method (50%, 93/186). The percentage of elderly subjects on continent
      spontaneous defecation (36.4%) was significantly less than that of the young
      group (66.7%; P<0.05). Furthermore, the percentage of elderly patients who
      required no bowel care (18.2%) was significantly less than those of the young
      (53.3%) and middle-age groups (41.1%; P<0.01). However, few differences in bowel
      care-related ADL were recognized among the three groups in patients who required
      manual emptying. CONCLUSION: The results identified significantly fewer patients
      aged >=70 years with 'continent spontaneous defecation' or 'independent for bowel
      care' compared with younger patients. The results also highlighted the clinical
      importance of bowel dysfunction associated with TCCS especially in elderly
      people.

PMID- 21876553
TI  - Mycobacterium abscessus activates the NLRP3 inflammasome via Dectin-1-Syk and
      p62/SQSTM1.
AB  - Numerous atypical mycobacteria, including Mycobacterium abscessus (Mabc), cause
      nontuberculous mycobacterial infections, which present a serious public health
      threat. Inflammasome activation is involved in host defense and the pathogenesis
      of autoimmune diseases. However, inflammasome activation has not been widely
      characterized in human macrophages infected with atypical mycobacteria. Here, we
      demonstrate that Mabc robustly activates the nucleotide binding and
      oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3)
      inflammasome via dectin-1/Syk-dependent signaling and the cytoplasmic scaffold
      protein p62/SQSTM1 (p62) in human macrophages. Both dectin-1 and Toll-like
      receptor 2 (TLR2) were required for Mabc-induced mRNA expression of pro
      interleukin (IL)-1beta, cathelicidin human cationic antimicrobial protein-18/LL
      37 and beta-defensin 4 (DEFB4). Dectin-1-dependent Syk signaling, but not that of
      MyD88, led to the activation of caspase-1 and secretion of IL-1beta through the
      activation of an NLRP3/apoptosis-associated speck-like protein containing a
      caspase recruitment domain (ASC) inflammasome. Additionally, potassium efflux was
      required for Mabc-induced NLRP3/ASC inflammasome activation. Furthermore, Mabc
      induced p62 expression was critically involved in NLRP3 inflammasome activation
      in human macrophages. Finally, NLRP3/ASC was critical for the inflammasome in
      antimicrobial responses to Mabc infection. Taken together, these data demonstrate
      the induction mechanism of the NLRP3/ASC inflammasome and its role in innate
      immunity to Mabc infection.

PMID- 21876554
TI  - New role for an established drug? Bisphosphonates as potential anticancer agents.
AB  - As a result of their ability to effectively reduce the risk of skeletal-related
      events, bisphosphonates (BPs) were incorporated into clinical practice over a
      decade ago, leading to a new treatment paradigm for patients with skeletal
      involvement from advanced cancer. BPs are now a well-established treatment option
      in this setting. Our review of the literature found that in addition to
      maintaining bone health in patients with malignant bone lesions and patients at
      risk for cancer therapy-induced bone loss, emerging preclinical and clinical data
      suggest that BPs may also have anticancer activity. Later generation, nitrogen
      containing BPs (N-BPs), such as zoledronic acid (ZOL), inhibit the mevalonate
      pathway, subsequently inhibiting a number of cellular functions in bone-resorbing
      osteoclasts. In addition, N-BPs inhibit cancer cell proliferation, viability,
      motility, invasion and angiogenesis; induce cancer cell apoptosis; and act in
      synergy with antineoplastic agents. N-BPs, especially ZOL, may be useful as
      anticancer agents. As evidence continues to emerge, another shift in cancer
      treatment paradigms, in which N-BPs are considered for their anticancer activity
      as well as palliative effects, may be approaching.

PMID- 21876556
TI  - Investigating the bona fide differentiation capacity of human pluripotent stem
      cells.

PMID- 21876555
TI  - Normal and disease-related biological functions of Twist1 and underlying
      molecular mechanisms.
AB  - This article reviews the molecular structure, expression pattern, physiological
      function, pathological roles and molecular mechanisms of Twist1 in development,
      genetic disease and cancer. Twist1 is a basic helix-loop-helix domain-containing
      transcription factor. It forms homo- or hetero-dimers in order to bind the Nde1 E
      box element and activate or repress its target genes. During development, Twist1
      is essential for mesoderm specification and differentiation. Heterozygous loss-of
      function mutations of the human Twist1 gene cause several diseases including the
      Saethre-Chotzen syndrome. The Twist1-null mouse embryos die with unclosed cranial
      neural tubes and defective head mesenchyme, somites and limb buds. Twist1 is
      expressed in breast, liver, prostate, gastric and other types of cancers, and its
      expression is usually associated with invasive and metastatic cancer phenotypes.
      In cancer cells, Twist1 is upregulated by multiple factors including SRC-1,
      STAT3, MSX2, HIF-1alpha, integrin-linked kinase and NF-kappaB. Twist1
      significantly enhances epithelial-mesenchymal transition (EMT) and cancer cell
      migration and invasion, hence promoting cancer metastasis. Twist1 promotes EMT in
      part by directly repressing E-cadherin expression by recruiting the nucleosome
      remodeling and deacetylase complex for gene repression and by upregulating Bmi1,
      AKT2, YB-1, etc. Emerging evidence also suggests that Twist1 plays a role in
      expansion and chemotherapeutic resistance of cancer stem cells. Further
      understanding of the mechanisms by which Twist1 promotes metastasis and
      identification of Twist1 functional modulators may hold promise for developing
      new strategies to inhibit EMT and cancer metastasis.

PMID- 21876558
TI  - K-ras(G12V) transformation leads to mitochondrial dysfunction and a metabolic
      switch from oxidative phosphorylation to glycolysis.
AB  - Increased aerobic glycolysis and oxidative stress are important features of
      cancer cell metabolism, but the underlying biochemical and molecular mechanisms
      remain elusive. Using a tetracycline inducible model, we show that activation of
      K-ras(G12V) causes mitochondrial dysfunction, leading to decreased respiration,
      elevated glycolysis, and increased generation of reactive oxygen species. The K
      RAS protein is associated with mitochondria, and induces a rapid suppression of
      respiratory chain complex-I and a decrease in mitochondrial transmembrane
      potential by affecting the cyclosporin-sensitive permeability transition pore.
      Furthermore, pre-induction of K-ras(G12V) expression in vitro to allow metabolic
      adaptation to high glycolytic metabolism enhances the ability of the transformed
      cells to form tumor in vivo. Our study suggests that induction of mitochondrial
      dysfunction is an important mechanism by which K-ras(G12V) causes metabolic
      changes and ROS stress in cancer cells, and promotes tumor development.

PMID- 21876559
TI  - Axing Wnt signals.

PMID- 21876557
TI  - Dynamic chromatin states in human ES cells reveal potential regulatory sequences
      and genes involved in pluripotency.
AB  - Pluripotency, the ability of a cell to differentiate and give rise to all
      embryonic lineages, defines a small number of mammalian cell types such as
      embryonic stem (ES) cells. While it has been generally held that pluripotency is
      the product of a transcriptional regulatory network that activates and maintains
      the expression of key stem cell genes, accumulating evidence is pointing to a
      critical role for epigenetic processes in establishing and safeguarding the
      pluripotency of ES cells, as well as maintaining the identity of differentiated
      cell types. In order to better understand the role of epigenetic mechanisms in
      pluripotency, we have examined the dynamics of chromatin modifications genome
      wide in human ES cells (hESCs) undergoing differentiation into a mesendodermal
      lineage. We found that chromatin modifications at promoters remain largely
      invariant during differentiation, except at a small number of promoters where a
      dynamic switch between acetylation and methylation at H3K27 marks the transition
      between activation and silencing of gene expression, suggesting a hierarchy in
      cell fate commitment over most differentially expressed genes. We also mapped
      over 50 000 potential enhancers, and observed much greater dynamics in chromatin
      modifications, especially H3K4me1 and H3K27ac, which correlate with expression of
      their potential target genes. Further analysis of these enhancers revealed
      potentially key transcriptional regulators of pluripotency and a chromatin
      signature indicative of a poised state that may confer developmental competence
      in hESCs. Our results provide new evidence supporting the role of chromatin
      modifications in defining enhancers and pluripotency.

PMID- 21876560
TI  - Mice generated from tetraploid complementation competent iPS cells show similar
      developmental features as those from ES cells but are prone to tumorigenesis.

PMID- 21876561
TI  - Influence of fluid therapy on the prognosis of acute pancreatitis: a prospective
      cohort study.
AB  - OBJECTIVES: Although aggressive fluid therapy during the first days of
      hospitalization is recommended by most guidelines and reviews on acute
      pancreatitis (AP), this recommendation is not supported by any direct evidence.
      We aimed to evaluate the association between the amount of fluid administered
      during the initial 24 h of hospitalization and the incidence of organ failure
      (OF), local complications, and mortality. METHODS: This was a prospective cohort
      study. We included consecutive adult patients admitted with AP. Local
      complications and OF were defined according to the Atlanta Classification.
      Persistent OF was defined as OF of >48-h duration. Patients were divided into
      three groups according to the amount of fluid administered during the initial 24
      h: group A: <3.1 l (less than the first quartile), group B: 3.1-4.1 l (between
      the first and third quartiles), and group C: >4.1 l (more than the third
      quartile). RESULTS: A total of 247 patients were analyzed. Administration of >4.1
      l during the initial 24 h was significantly and independently associated with
      persistent OF, acute collections, respiratory insufficiency, and renal
      insufficiency. Administration of <3.1 l during the initial 24 h was not
      associated with OF, local complications, or mortality. Patients who received
      between 3.1 and 4.1 l during the initial 24 h had an excellent outcome.
      CONCLUSIONS: In our study, administration of a small amount of fluid during the
      initial 24 h was not associated with a poor outcome. The need for a great amount
      of fluid during the initial 24 h was associated with a poor outcome; therefore,
      this group of patients must be carefully monitored.

PMID- 21876562
TI  - Hepatitis B immunity and response to booster vaccination in children with
      inflammatory bowel disease treated with infliximab.
AB  - OBJECTIVES: Hepatitis B virus (HBV) reactivation has been described in patients
      treated with infliximab for inflammatory bowel disease (IBD). This has resulted
      in a "black box" warning. Although universal vaccination against hepatitis B was
      implemented in the United States in 1991, up to 10% of vaccine recipients fail to
      respond with adequate anti-hepatitis B surface antibodies (anti-HBs) levels after
      a primary series of vaccinations. In addition, anti-HBs levels are expected to
      decline with time. The objectives of this study were to determine HBV immunity in
      children with IBD on infliximab therapy and to determine response to a booster
      dose of the HBV vaccine in patients who were found to be non-immune. METHODS:
      This was a prospective cross-sectional, single-center study that included 100
      pediatric IBD patients on infliximab. Serologic specimens were tested for
      hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), and
      anti-HBs. Patients with an anti-HBs level >=10 mIU/ml were considered to be
      immune. One booster dose was given to non-immune patients and a serum sample was
      collected after 4 weeks to assess the presence of anamnestic response (anti-HBs
      level >=10 mIU/ml after booster). RESULTS: The mean age of the patients was 17.9
      (+/-4.0) years. None of the patients were positive for HBsAg or anti-HBc. In all,
      87 patients were vaccinated against HBV and 49/87 (56%) had immunity to HBV as
      defined by anti-HBs level >=10 mIU/ml. The mean concentration of anti-HBs levels
      in immune patients was 295.6 (+/-350.6) mIU/ml. Older age, lower albumin levels,
      and the presence of pancolitis were associated with the absence of protective
      antibodies; however, infliximab dose, frequency, duration, and the concurrent use
      of immunomodulators were not significantly different between immune and non
      immune patients. Thirty-four patients received booster immunization and 26/34
      (76%) had an anamnestic response. Interestingly, non-responders were given
      infliximab with higher frequency (every 5.9 +/- 1.2 weeks vs. every 7.1 +/- 1.8
      weeks, P=0.01). Overall, 75/87 (86%) of previously immunized patients were
      considered immune against HBV infection. CONCLUSIONS: In pediatric IBD patients
      seen at a large, urban tertiary care facility in the United States, a significant
      minority (13%) have not been vaccinated against HBV. Nearly one-half of all
      patients (and 44% of previously vaccinated patients) did not have protective anti
      HBs levels. Moreover, of those previously vaccinated, a significant minority
      (14%) appear at risk for HBV because protective anti-HBs levels were absent and
      could not be elicited through booster immunization. Given the high risk for
      severe HBV infection in this group, efforts should be made to screen for HBV
      immunity at the time of IBD diagnosis. Booster immunization should be considered
      in patients without protective antibodies.

PMID- 21876563
TI  - Detection of KRAS gene mutations in endoscopic ultrasound-guided fine-needle
      aspiration biopsy for improving pancreatic cancer diagnosis.
AB  - OBJECTIVES: Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB)
      is a useful tool in the diagnosis of pancreatic masses. Genetic analysis of these
      samples could increase the sensitivity and specificity of diagnosis. This study
      aimed to evaluate the usefulness of a novel method for the detection of mutations
      in the KRAS (Kirsten rat sarcoma-2 virus) gene for the diagnosis of pancreatic
      cancer. METHODS: EUS-FNABs were performed on 82 patients with pancreatic masses,
      including 54 cases of pancreatic ductal adenocarcinoma and 28 of non-malignant
      pancreatic masses. The biopsies were histopathologically and cytopathologically
      evaluated, and the detection of KRAS gene mutations (codons 12 and 13) was
      performed through peptide nucleic acid-directed polymerase chain reaction
      clamping and DNA sequencing. RESULTS: In the pancreatic cancer cases, 88.9%
      (48/54; 95% confidence interval (CI): 80.5-97.2%) had KRAS mutations, while 61.1%
      (33/54; 95% CI: 48.1-74.1%) were unequivocally diagnosed by histo/cytopathology.
      In the indeterminate patients (n=49; diagnosed by EUS-FNA as either insufficient
      material to make a diagnosis, no malignancy, or suspicion of malignancy), there
      were 10 cases of pancreatic cancer with low serum carbohydrate antigen 19-9 (CA19
      9) (<37 U/l) and 6 of these were KRAS mutations. The sensitivity of detection by
      KRAS mutations (76.2%) and the combination of KRAS mutations and serum CA19-9
      (81%) were significantly higher than for serum CA19-9 alone (52.4%). A logistic
      regression model showed that the KRAS mutation was significant (odds ratio=5.830;
      CI: 1.531-22.199, P=0.01), but not serum CA19-9. In the non-malignant pancreatic
      masses (n=28), KRAS mutations were detected in nine precancerous lesions.
      CONCLUSIONS: Our method for the detection of KRAS gene mutations may be useful to
      supplement histo/cytopathologic evaluations for pancreatic cancer, and is
      superior to serum CA19-9 in EUS-FNAB histo/cytopathology-indeterminate patients.
      Results warrant further verification in other patient populations.

PMID- 21876565
TI  - Use of ureterorenoscope as choledochoscope.
AB  - BACKGROUND: Flexible Choledochoscope is used to remove the stones using
      accessories during exploration of the common bile duct and its use reduces the
      incidence of retained stones. The choledochoscope and accessories are expensive
      and not available in many General Hospitals. In comparison to this, semi-rigid
      ureterorenoscope is easily available in many minimally invasive centres and
      accessories are more useful to remove even the impacted stones. We have used this
      for exploration of the CBD and tried to analyse its efficacy and safety. METHODS:
      All the patients who underwent ureterorenoscopic intervention by single surgeon
      for common bile duct stones during 2007-2010 are included. The usefulness,
      efficacy and safety of the procedure are analysed. RESULTS: There were total 71
      patients. Age ranges from 10 years to 69 years. Forty one (57.7%) patients had
      undergone open procedure where as 30 (42.2%) underwent laparoscopic procedure.
      Most of them were females (69%) and majority had multiple stones (59%). Twenty
      five (35%) patients required the use of different accessories like dormia basket,
      forceps etc. Pneumatic lithotripsy was used in 3 patients to fragment large
      impacted stones. In one (3%) patient of laparoscopic group scope could not be
      negotiated. In 4 cases mild common bile duct tear observed and in one patient
      duodenal laceration occurred. In two patients (2.8%) there were retained small
      stone fragments which passed spontaneously within two weeks post-operatively.
      CONCLUSIONS: Semirigid ureterorenoscope is easily available, safe and effective
      instrument. It is useful even for large impacted stones.

PMID- 21876564
TI  - Effects of A3309, an ileal bile acid transporter inhibitor, on colonic transit
      and symptoms in females with functional constipation.
AB  - OBJECTIVES: Delivery of bile acid (BA) to the colon stimulates propulsive
      motility and fluid secretion. The objective of this study was to examine
      gastrointestinal (GI) transit effects of A3309, a small molecule inhibitor of the
      ileal BA transporter, in patients with functional constipation (FC). METHODS: In
      a double-blind, placebo-controlled study of 36 female FC patients randomized to
      placebo, 15 mg A3309, or 20 mg A3309 administered orally once daily for 14
      consecutive days, we assessed GI and colonic transit, stool characteristics,
      symptoms of constipation, fasting serum C4 (7alpha-hydroxy-4-cholesten-3-one)
      (surrogate of BA synthesis and malabsorption), and fasting serum total and low
      density lipoprotein (LDL) cholesterol (surrogates of inhibition of BA
      absorption). Following the intention-to-treat paradigm, we used analysis of
      covariance to assess the overall treatment effects and Dunnett's test for
      pairwise comparisons. RESULTS: Overall colonic transit (geometric center at 24 h)
      was significantly accelerated with 20 mg A3309 compared with placebo (overall
      effect, P=0.059; A3309 15 mg, P=0.18; and A3309 20 mg, P=0.04). Colonic transit
      at 48 h was significantly accelerated with both A3309 dosages (overall effect,
      P<0.001; A3309 15 mg, P=0.002; and A3309 20 mg, P<0.001). Significantly looser
      stool consistency was noted with both A3309 dosages compared with placebo
      (P<0.005). Significant effects of A3309 on constipation rating, ease of stool
      passage, and reduction of straining were also detected. The most common side
      effect was lower abdominal cramping/pain. A3309 treatment significantly and
      reversibly increased fasting C4 (A3309 15 mg, P=0.05; A3309 20 mg, P<0.01) but
      did not affect fasting total and LDL cholesterol. CONCLUSIONS: A3309 accelerates
      colonic transit and loosens stool consistency in FC patients.

PMID- 21876566
TI  - Pandemic influenza A (H1N1) 2009 outbreak investigation in Nepal.
AB  - BACKGROUND: The World Health Organization, on 24 April 2009, announced a Public
      Health emergency of international concern caused by a new influenza virus
      Pandemic Influenza A 2009. The objective of this study was to analyze the basic
      epidemiology and distribution of Pandemic Influenza A 2009 in order to understand
      the course of Pandemic Influenza A 2009 in Nepal. METHODS: The analyses were
      based upon all confirmed and probable cases that consulted Avian Influenza
      Control Project and National Public Health Laboratory during 29 April 2009 to 21
      September 2010. RESULTS: Out of total 739 suspected samples collected, Pandemic
      Influenza A 2009 was detected in 210 cases in different districts of Nepal. The
      majority of cases were from the urban settlement of Kathmandu valley, Chitwan and
      Kaski and among age group 11-30 years. The clinical attack rate for Influenza
      like illness (ILI) was 28.48%. There was no significant difference between the
      clinical presentation of ILI and confirmed cases of Pandemic Influenza A 2009.
      CONCLUSIONS: This study presented the investigation of outbreak that helped to
      inform the course of epidemic in affected population and therefore urge for
      public health interventions.

PMID- 21876567
TI  - Serum gamma glutamyl transferase and alkaline phosphatase in acute cholecystitis.
AB  - BACKGROUND: The serum level of gamma glutaryl transferase and alkaline
      phosphatase is raised in acute calculus cholecystitis and common bile duct stone.
      However, the rise in serum level of these enzymes in acute cholecystitis implies
      stone in the common bile duct is not well studied. Thus, it may lead to retained
      CBD stone on one side and unnecessary CBD exploration on the other during
      emergency laparoscopic cholecystectomy. The objective of the study is to predict
      presence of CBD stone by assessing serum level of gamma-glutamyltransferase
      (gamma-GT)and alkaline phosphatase. METHODS: A prospective study was designed
      which included 40 patients with clinically diagnosed and radiologically confirmed
      acute cholecystitis and 40 patients who had choledocholithiasis with or without
      cholangitis. Their serumgamma glutaryl transferase and alkaline phosphatase were
      analyzed. RESULTS: Both acute cholecystitis and CBD pathology had significant
      increase in alkaline phosphatase (p-value: 0.05). However, in acute cholecystitis
      there was 1.69+/-0.118 fold increase and in CBD pathology there was 2.5+/-0.57
      fold increase in alkaline phosphatase than normal.(130 IU /L). There was no
      statistically significant difference ingamma- GT in both acute cholecystitis and
      CBD pathology(p-value: 0.390). However it increases by 2.8+/-0.47fold in acute
      cholecystitis and by 2.2+/-0.16 in CBD pathology(p value: 0.627). CONCLUSIONS:
      Although there is rise in serumgamma-GT and alkaline phosphatase level in acute
      cholecystitis and CBD stone,only more than 2.5 fold rise in serum alkaline
      phosphatase level predicts CBD stone.

PMID- 21876568
TI  - Job satisfaction among nurses in a hospital.
AB  - BACKGROUND: Nursing is one of the stressful jobs in health sector. The level of
      job satisfaction in the profession remains a matter of concern. This study means
      to explore the job satisfaction among the nurses of Dhulikhel Hospital. METHODS:
      A Descriptive cross sectional study design was conducted in Dhulikhel Hospital; a
      community based Hospital of Nepal Health Research Council from January to
      December 2009. All the nursing staffs that consented to the study filled up a
      standard questionnaire. RESULTS: A total of 85 nurses completed the study. The
      mean age of the respondents' was 23. 80.6% of the nursing staffs were satisfied.
      "Being considered a resource of health" provided highest sense of satisfaction,
      while "Lack of opportunities for further education and training" provided lowest
      sense of satisfaction. CONCLUSIONS: Majority of the nurses were satisfied with
      their present condition of work. Since job satisfaction is a dynamic process, the
      result may not be static or consistence. Working environment and employees
      expectations should receive attention.

PMID- 21876569
TI  - Health care waste management practice in a hospital.
AB  - BACKGROUND: Health-care waste is a by-product of health care. Its poor management
      exposes health-care workers, waste handlers and the community to infections,
      toxic effects and injuries including damage of the environment. It also creates
      opportunities for the collection of disposable medical equipment, its re-sale and
      potential re-use without sterilization, which causes an important burden of
      disease worldwide. The purpose of this study was to find out health care waste
      management practice in hospital. METHODS: A cross-sectional study was conducted
      in Narayani Sub-Regional Hospital, Birgunj from May to October 2006 using both
      qualitative and quantitative methods. Study population was four different
      departments of the hospital (Medical/Paediatric, Surgical/Ortho, Gynae/Obstetric
      and Emergency), Medical Superintendent, In-charges of four different departments
      and all sweepers. Data was collected using interview, group discussion,
      observation and measurement by weight and volume. RESULTS: Total health-care
      waste generated was 128.4 kg per day while 0.8 kg per patient per day. The
      composition of health care waste was found to be 96.8 kg (75.4%) general waste,
      24.1 kg (8.8%) hazardous waste and 7.5 kg (5.8%) sharps per day by weight. Health
      staffs and sweepers were not practicing the waste segregation. Occupational
      health and safety was not given due attention. Majority of the sweepers were
      unaware of waste management and need of safety measures to protect their own
      health. CONCLUSIONS: Health care waste management practice in the hospital was
      unsatisfactory because of the lack of waste management plan and carelessness of
      patients, visitors and staffs. Therefore the hospital should develop the waste
      management plan and strictly follow the National Health Care Waste Management
      Guideline.

PMID- 21876570
TI  - A 5 year clinical experience of laparoscopic appendicectomy.
AB  - BACKGROUND: Although laparoscopic appendicectomy is now a common practice, it has
      not become the gold standard like in cholecystectomy. Aim of our study is to
      compare with operation time and hospital stay found in available literatures.
      METHODS: All laparoscopic appendicectomies performed between January 2004 and
      February 2009 were retrospectively reviewed for age, sex and operation time
      length and hospital stay. Appendicitis with signs of perforation was treated by
      open midline laparatomy and the ones with lump formation were treated
      conservatively. RESULTS: A total of 48 patients underwent laparoscopic
      appendicectomies during this period (female 26 and male 22) and mean age was 27.2
      years (6-77). The mean operating time was 56.6 minutes (40-120 minutes). The mean
      hospital stay was 4.7 days (3-8 days). CONCLUSIONS: Laparoscopic appendicectomy
      is a feasible and safe in simple appendicitis. Although the number of cases of
      laparoscopic appendicectomies is a small for five year period, the mean operation
      time and mean hospital stay is comparable to the literatures.

PMID- 21876571
TI  - Fertility desire of working women in Kathmandu.
AB  - BACKGROUND: This study is done to describe the fertility pattern and factors
      associated with unmet desire for additional children among women working in
      formal and informal sector in Kathmandu, Nepal. METHODS: This is a cross
      sectional study. Married 177 women in reproductive age group, with at least one
      child are selected using purposive sampling. Housewives without paid job are
      excluded. Interview using semi structured questionnaire is conducted. RESULTS:
      Around 14 percent of women want additional children, however due to various
      reasons they do not intend to have another. Women in age group of 25-29 followed
      by 30-34 years of age have higher desire for more children as compared to women
      in more than 40 years of age. Women who earn 25000-33000 Rupees per month have
      significantly more desire for another child. CONCLUSIONS: Childcare time and
      economic conditions play vital role in fertility desire among working women.
      Family help is available to most of the women to care their children. These women
      wish more facilities at workplace during child bearing and rearing period.

PMID- 21876572
TI  - Caudal bupivacaine vs bupivacaine plus tramadol in post-operative analgesia in
      children.
AB  - BACKGROUND: Caudal analgesia with bupivacaine is used commonly for pain relief in
      children and extradural administration of tramadol seemed to be a safe method of
      analgesia. The aim of the study is to compare the analgesic efficacy of caudal
      bupivacaine and bupivacaine and tramadol mixture for postoperative analgesia and
      to observe for side effects. METHODS: Forty children, aged between 1- 6 years
      undergoing infra umbilical surgeries were selected for this randomized, control
      trial. They were randomly divided into two groups. Group A (n = 20) received 0.5
      ml/kg of 0.25 % bupivacaine and Group B (n = 20) received 0.5 ml/kg of 0.25 %
      bupivacaine with 1 mg/kg of tramadol as a single shot caudal block. In the
      postoperative period heart rate, respiratory rate, pain score, recovery to first
      analgesic time, total number of analgesics required in 24 hours and side effects
      were noted and analyzed. RESULTS: It was observed that the mean duration of pain
      relief was significantly longer in Group B (8.8 hrs Vs 7 hrs). Nausea and
      vomiting was observed in 25% of the patients in group B and 20 % of the patients
      in group A. None of the patients in both the groups had complication like motor
      weakness, urinary retention in the postoperative period. CONCLUSIONS: The
      addition of tramadol to bupivacaine in the caudal analgesic technique provides
      longer analgesia and lesser need for rescue analgesic in the postoperative period
      compared to bupivacaine.

PMID- 21876573
TI  - Scenario of HIV/AIDS patients in a government hospital of Nepal.
AB  - BACKGROUND: With the increase in the severity of immunosupression, due to HIV
      infection, there is increase in the flow of patients seeking care and support
      services. Antiretroviral drugs minimize chance of developing AIDS related
      opportunistic infection and therefore there would be the prolongation of life of
      the patients. The objectives of this study are to assess the chief complaints,
      major opportunistic infections, complications of ART and treatment outcome of
      hospital admitted HIV patients. METHODS: A cross sectional study was carried out
      between December 2008 to May 2009 among 66 HIV patients undergoing indoor
      treatment in Seti Zonal Hospital, Dhangadhi. RESULTS: Of the total cases, 36
      (54.5%) were male and 30 (45.5%) were females with predominant age group of 31-
      40 years (47%). About 24% of admitted patients had CD4 count less than 50/cu mm
      blood. Thirty five (53%) cases presented fever as the major clinical presentation
      of HIV/AIDS due to different opportunistic infections followed by cough (28.8%),
      loss of appetite (28.8%), weight loss (27.3%), and diarrhea (24.2%). Tuberculosis
      was found to be the major opportunistic infection accounting 27.3% followed by
      gastroenteritis (21.2%) and oral candidiasis (15.5%). Treatment outcome of
      hospital admitted patients showed the 83.3% recovery rate and 4.3% death rate.
      CONCLUSIONS: Hospital admission was found to be efficient to treat the major
      opportunistic infections and management of ART hypersensitivity reactions. While
      tuberculosis was the leading opportunistic infection, the most common clinical
      manifestation was found to be fever among the admitted HIV/AIDS patients.

PMID- 21876574
TI  - Bacteriuria and urinary retention following gynaecological surgery: comparing
      short vs long term catheterization.
AB  - BACKGROUND: Post operative bladder drainage is important care following
      gynaecological surgeries. This study was done to compare the incidence of urinary
      retention and bacteriuria following long term versus short term catheterization.
      METHODS: The patients who were admitted for gynaecological major surgeries were
      enrolled in this study. One group of patients had post operative indwelling
      catheterization for 24 hrs (short term catheterization) and another group of
      patients had catheterization for more than 48 hrs (long term catheterization).
      The urine examination and culture sensitivity was sent for all patients at the
      removal of catheter. The patients were followed after removal of catheter for
      urinary retention. RESULTS: Total of 102 patients were studied. There were 48
      patients in short term catheterization group and 54 patients in long term
      catheterization group. In short term catheterization group, 3 (6.2%) cases had
      bacteriuria and no cases of urinary retention were observed. In prolonged
      catheterization group, 6 cases (11.1%) had bacteriuria and 2 cases (3.7%) had
      urinary retention. CONCLUSIONS: This study has concluded that short time
      catheterization following gynaecological surgery had fewer incidences of
      bacteriuria and urinary retention than long term catheterization.

PMID- 21876575
TI  - Microalbuminuria and macroalbuminuria in type 2 diabetes.
AB  - BACKGROUND: Type 2 diabetes is the leading cause of end stage renal disease
      worldwide. Prevalence of diabetic nephropathy (DN) varies in the different ethnic
      groups. Nepal is country with great ethnic diversity. This study has been done to
      find the prevalence of microalbuminuria and macroalbuminuria in the two ethnic
      groups Jyapu and Brahmin. METHODS: In our study we have included two ethnic
      groups Jyapu and Brahmin type 2 diabetic patients. INCLUSION CRITERIA: Age >= 30
      years, clinically diagnosed type 2 diabetic patients. EXCLUSION CRITERIA:
      Patients with a history of urinary tract infection, hematuria, renal failure,
      intercaste marriage and women with menstruation at the time of sample collection.
      RESULTS: The overall prevalence of albuminuria was 49.05%. The prevalence of
      microalbuminuria was 35.89% in Jyapu and 37.73% in Brahmin which was comparable.
      There was significantly higher prevalence of macroalbuminuria in Jyapu 20.75% and
      Brahmin 3.77%. Association of dietary habit was seen with microalbuminuria and
      macroalbuminuria in both ethnic groups. CONCLUSIONS: The overall prevalence of
      albuminuria in type 2 diabetes of our study was high and there was significantly
      higher macroalbuminuria in Jyapu compared with Brahmin. It, therefore, predicts a
      higher risk of having kidney disease in Jyapu population.

PMID- 21876576
TI  - Dilemma of medical graduates in Nepal.
AB  - The medical education system is in infancy in Nepal. There are many constrains at
      various levels. The numbers of medical colleges are increasing every year without
      considering for its quality by the concerned authorities. Nepal Medical Council
      is the authorized body to look for medical professionals in the country. Even
      though, efforts have been made from various sectors but are insufficient. This
      article will mainly focus on the life of a medical graduate in Nepal. It will
      give an idea of how these graduates have to undergo various problems regarding
      their career, family, profession and social lives, right after their graduation.

PMID- 21876577
TI  - Prostatic abscess a diagnostic dilemma.
AB  - Abscess of the prostate has become increasingly rare due to modern antibiotics
      and a decreasing incidence of gonococcal infections. It is still difficult to
      diagnose the disorder on clinical grounds. Diagnosis is often made after
      Ultrasound examination. We report 2 cases of prostatic abscess and review
      etiopathogenic factors, clinical findings, diagnosis and treatment of this
      uncommon entity.

PMID- 21876578
TI  - An unusual presentation of acute coronary syndrome.
AB  - Acute coronary syndrome in elderly can manifest with a variety of atypical
      presentation and may be associated with other comorbid conditions. We present an
      atypical presentation of ACS in an elderly left handed female presenting with
      sudden onset of slurred speech preceded by dizziness and vomiting. After through
      clinical examination and investigation she was managed as a case of non ST
      elevation myocardial infarction and ischaemic stroke.

PMID- 21876579
TI  - The macular edema.

PMID- 21876580
TI  - Clinical profile and visual outcome following pars plana vitrectomy in acute post
      operative endophthalmitis.
AB  - INTRODUCTION: Endophthalmitis following cataract surgery is a rare but
      devastating ocular complication where delay in treatment not only results in
      vision loss but also in difficulty to save the eye ball. OBJECTIVE: To explore
      the clinical profile and visual outcome following pars plana vitrectomy (PPV) in
      acute endophthalmitis after cataract surgery. MATERIALS AND METHODS: This is a
      retrospective interventional case series study conducted at Tilganga Institute of
      Ophthalmology (TIO), Nepal. All consecutive cases of acute endophthalmitis
      following cataract surgery treated with PPV from January 2005 to August 2010 were
      included in the study. RESULTS: There were a total of 34 cases (34 eyes) treated
      with PPV. The age range was 8 - 93 years with mean age of 56.9 +/- 19.5 years.
      The mean duration of presentation and duration following cataract surgery was 7.7
      +/- 8.1 days and 13 +/- 11.6 days respectively. Small incision cataract surgery
      was done in 75 % of cases followed by phacoemulsification (15.6 %). The mean
      duration of the last follow -up was 4.3 months. Vision was improved in two-thirds
      of cases (67.67 %) with a good vision of 6/18 or better in 17.6 %. Among the
      available vitreous samples of 22 cases, 36.36 % had an abnormality in Gram and
      Giemsa stains and culture was positive in 13.6 % of cases. CONCLUSION: Despite
      the late presentation, the majority of eyes were salvaged with improvement of
      vision in 67.67 %, with a good vision of 6/18 or better in 17.6 4 % of cases
      following PPV in acute post operative endophthalmitis.

PMID- 21876581
TI  - Scleral buckle surgery for pseudophakic and aphakic retinal detachment in western
      Nepal.
AB  - INTRODUCTION: Retinal detachment remains one of the most serious complications of
      cataract surgery. Treatment of this condition has represented a challenge for
      vitreoretinal surgeons.Scleral buckle (SB) surgery is one of the treatment
      options in pseudophakic and aphakic retinal detachment (RD). AIMS: To find out
      the anatomical and visual outcome of SB in pseudophakic and aphakic RD. SUBJECTS
      AND METHODS: Retrospective case series of 46 consecutive eyes of 46 patients with
      RD (38 pseudophakic and 8 aphakic eyes) that had undergone conventional SB
      surgery were reviewed from patient files. Postoperative retinal status at 3
      weeks, 6 weeks and 3 months were recorded to see the anatomical success rate
      after retinal reattachment surgery. Best corrected visual acuity (BCVA) at 3
      months follow-up was noted. RESULTS: The mean age of the patients was 54.28 +/-
      13.49 years. Forty eyes (86.9 %) had primary attachment by 6 weeks duration. Five
      eyes had undergone repeat surgery within a six-week duration (pars plana
      vitrectomy). Forty patients had follow-up visit to 12 weeks, achieving retinal
      attachment in 37 eyes (80.5 %). Best corrected visual acuity (BCVA) at 3 months
      was better than 6/60 in 18 eyes (39.1%), BCVA better or equal to 1/60 but less
      than 6/60 in 18 eyes (39.1%) and BCVA less than 1/60 in 4 eyes (8.7 %).
      CONCLUSION: Conventional scleral buckling has good outcome for pseudophakic and
      aphakic RD and can be useful for patients in peripheral eye hospitals where
      patients cannot afford high cost surgeries.

PMID- 21876582
TI  - Alport Syndrome: case report and review of ocular manifestations.
AB  - BACKGROUND: Alport Syndrome is an uncommon disease. CASE: We report a case of a
      young Indian male who presented with the characteristic ocular findings and
      systemic features of Alport Syndrome. CONCLUSION: Any young patient with a
      chronic renal disease should have a careful ophthalmologic examination for Alport
      Syndrome.

PMID- 21876583
TI  - Pattern of fungal isolates in cases of corneal ulcer in the western periphery of
      Nepal.
AB  - PURPOSE: To find out the epidemiologic features in 686 consecutive cases of
      fungal keratitis presenting in a tertiary eye hospital in the western region of
      Nepal. MATERIALS AND METHODS: A prospective hospital - based study was carried
      out on 1880 consecutive patients presenting with corneal ulcer in the outpatient
      department and cornea clinic of Lumbini Eye Institute, Bhairawa, Nepal. The socio
      demographic data, predisposing risk factors, prior treatment modalities,
      laboratory results and the distribution pattern of fungus species were analyzed.
      RESULTS: Diagnosis of fungus keratitis was established in 686 (36 %) out of the
      total study group of 1880 cases. The spectrum of fungi isolated were Fusarium
      species (Fusarium spp.) in 219 (31.9 %), followed by unidentified dematiaceous
      151 (22 %), curvularia 122 (17.7 %) and unidentified hyaline in 111 cases (16.1
      %). Men (59.3 %) were more commonly affected than women (40.6 %). The young
      adults age group of 31-40 years was most commonly involved (26.6 %). Corneal
      trauma (58 %) and topical steroids (12 %) were the most common predisposing risk
      factors noted. CONCLUSION: In contrast to the other studies done in Nepal, we
      found Fusarium to be the most common fungal isolate causing corneal ulcer
      followed by unidentified dematiaceous, unidentified hyaline and curvularia.
      Corneal trauma was the commonest predisposing risk factor in causing fungal
      keratitis.

PMID- 21876584
TI  - Glaucoma at a tertiary referral eye hospital in Nepal.
AB  - BACKGROUND: Glaucoma is an important cause of blindness. OBJECTIVE: To report the
      distribution of various types of glaucoma among patients presenting to a tertiary
      eye hospital in Nepal. MATERIALS AND METHODS: All new patients visiting the
      hospital between March 2007 and February 2008 underwent a comprehensive eye
      examination. Whenever glaucoma was suspected, patients were referred to
      fellowship-trained glaucoma specialists. Patients received a comprehensive
      glaucoma workup including applanation tonometry, stereoscopic examination of the
      optic nerve head performed by the glaucoma specialists, and a Humphrey visual
      field analysis (SITA 24 - 2). RESULTS: 447 patients were newly diagnosed with
      glaucoma. 171 (38.2 %) patients had primary open-angle glaucoma (POAG), while 143
      (32 %) had primary angle-closure glaucoma (PACG). The average age of presentation
      of patients with POAG was 65.78 +/- 9.1 years, while the average age for PACG
      patients was 54.6 +/-12.8 years. 30 (21 %) patients with PACG had acute angle
      closure on presentation, while 113 (79 %) had chronic angle closure glaucoma. 107
      (75 %) of these patients with PACG had visual acuity of less than 3/60 (20/400)
      in the worse eye at presentation. The most common form of secondary glaucoma was
      lens-induced (5.3 %), followed by neovascular (3.2 %) and uveitic glaucoma (3.2
      %). CONCLUSION: The most common glaucoma seen in a tertiary referral eye hospital
      of Nepal is primary open-angle glaucoma. Among the angle-closure glaucoma,
      chronic angle-closure is the most common. Lens-induced glaucoma is still the
      commonest cause of secondary glaucoma.

PMID- 21876585
TI  - Validation of performance of certified medical assistants in preschool vision
      screening examination.
AB  - INTRODUCTION: Preschool vision screening examination is still a new concept in
      Nepal. There is a need for developing cost-effective tools for detecting
      amblyogenic factors in Nepalese children. Certified medical assistants (CMA) are
      health personnel who work in village health posts. OBJECTIVE: To find out the
      effectiveness of vision screening by certified medical assistants using simple
      tools like an HOTV chart and the Red Reflex test. MATERIALS AND METHODS: A cross
      sectional and validation study was carried out in two phases. In the first phase,
      20 CMAs from each Village Development Centre (VDC) of the Bhaktapur District were
      given training on visual acuity test by using an HOTV chart, Bruckner test by
      using a retinoscope and the test for ocular alignment by a torch light. In the
      second phase, children aged 3 - 7 years were examined by trained certified
      medical assistants in five remote VDCs of Bhaktapur District. These children
      underwent the gold standard examination by two pediatric ophthalmologists blind
      to the CMAs+/- findings. RESULTS: The mean age of children was 5.26 +/- 376
      years. The overall sensitivity of certified medical assistants examination was 58
      % and the specificity was 98 %. While comparing the test characteristics of
      different examination tools, the HOTV test was found to be the most effective one
      with the sensitivity of 80 % and the specificity of 98 %. CONCLUSION: Vision
      screening by certified medical assistants can help in detection and early
      referral of children having amblyogenic risk factors with high sensitivity. The
      HOTV test is the most effective one with high sensitivity and specificity. In
      developing countries like Nepal,where access to regular eye examination is a rare
      possibility, preschool vision screening using the HOTV test can be effective.

PMID- 21876586
TI  - A comparative bacteriological profile and antibiogram of dacryocystitis.
AB  - INTRODUCTION: Dacryocystitis is an infection and an inflammation of the lacrimal
      sac and is an important cause of ocular morbidity in India. OBJECTIVE: To isolate
      and identify the bacterial patterns associated with dacryocystitis and to
      determine their antibacterial sensitivity pattern. MATERIALS AND METHODS: A total
      of 100 lacrimal swab materials were subjected to bacterial analysis. Children
      less than 8 years were not included in the study. RESULTS: The chances of chronic
      dacryocystitis were more than acute dacryocystitis and were commonly found in the
      age group of 41 - 50 years. Females were more vulnerable to the infection than
      males. From a 100 samples a total of 122 bacterial isolates were obtained. Both
      Gram positive and Gram negative bacteria were equally distributed in the study.
      The most common organism associated with the infection was S. aureus. The
      antibacterial sensitivity showed more effectiveness towards Gram positive
      isolates than Gram negative isolates. CONCLUSION: Both Gram positive and Gram
      negative organism are associated with with chronic dacryocystitis. Knowledge of
      the bacteriology of dacryocystitis and the susceptibility of the bacteria towards
      antibiotics will better guide a clinician in the choice of the medication for the
      most appropriate drug for the treatment.

PMID- 21876587
TI  - Evaluation of tear film stability before and after laser in situ keratomileusis.
AB  - OBJECTIVE: The study was conducted to evaluate tear film stability and tear
      secretion before and after laser in situ keratomileusis. MATERIALS AND METHODS:
      It was a prospective, longitudinal and non-comparative analysis of clinical data
      of 20 consecutive myopic patients (40 eyes) collected before and after laser in
      situ keratomileusis. Assessments included tear secretion (Schirmer I and II),
      fluorescein tear break up time and ocular surface staining. STATISTICS: The
      statistical package for social science (SPSS 10.0) was used for data analysis.
      The parameters of tear secretion and tear stability were analyzed using the
      paired and unpaired Student t-tests. RESULTS: Schirmer II was reduced at seven
      days (9.5 +/- 4.30 mm) and one month (10.3 +/- 3.06 mm, p=0.001) after operation
      from the pre-operative value of 16.12 +/- 3.90 mm. Tear film stability
      significantly decreased at seven days (6.79 +/- 3.05 sec, p Less than 0.001) and
      one month (8.03 +/- 2.81secs, p less than 0.001) from its pre-operative value
      (12.68 +/- 2.69 secs). 87.5% had tear film instability (FBUT less than 10secs)
      seven days after surgery; it was reduced to 75 % at one month and 27.5 % at three
      months. It was 7.5 % before surgery. Corneal staining score was increased
      significantly at seven days (1.42 +/- 1. 58, p less than 0.01) and one month
      (0.95 +/- 1.41, p=0.02), from the pre-operative score of 0.17 +/- 0.44.
      CONCLUSION: Laser in situ keratomileusis significantly alters the tear film
      stability, Schirmer values and corneal staining at least for three months.

PMID- 21876588
TI  - Accommodation: its relation to refractive errors, amblyopia and biometric
      parameters.
AB  - AIM: To study accommodation in relation to different refractive errors, amblyopia
      and to measure the anatomical changes in the accommodating eye MATERIALS AND
      METHODS: We studied the amplitude of accommodation (AA) in 150 patients in the
      age group 11 +/- 30 years which included emmetropes, myopes, hypermetropes and
      hypermetropic amblyopes using the Royal Air Force (RAF) rule. The anterior
      chamber depth (ACD), axial length (AxL) and lens thickness (LT) changes during
      accommodation were measured using an A-scan. Myopes and hypermetropes were
      further divided based on the amount of refractive error : less than 2D, 2 -4D and
      greater than 4D. RESULTS: Corrected low myopes had the highest accommodation
      amplitude (p less than 0.05) followed by emmetropes. Corrected hypermetropes were
      found to have the lowest amplitude of accommodation (p less than 0.05). The
      amblyopic eye had a significantly low AA compared to the non-amblyopic eye (p
      less than 0.05). ACD decreased (p less than 0.05) and LT increased (p less than
      0.05) during accommodation. The AxL increase was maximum in myopes (p less than
      0.05) followed by hypermetropes but the change was not significant in
      hypermetropes (p greater than 0.05). CONCLUSION: The amblyopic eye has low
      amplitudes of accommodation proving the benefit of near adds in amblyopic
      patients. Prolonged near work might induce myopia in susceptible eyes by
      increasing the axial length.

PMID- 21876589
TI  - Pterygium surgery with conjunctival limbal autograft with fibrin glue under
      topical anaesthesia with lignocaine 2% jelly.
AB  - OBJECTIVE: To evaluate the efficacy of lignocaine 2 % jelly as topical anesthesia
      in pterygium surgery with conjunctival limbal autograft using fibrin glue.
      MATERIALS AND METHODS: A non-randomized interventional study was carried out
      including twenty-one patients who presented with primary pterygium. Under 2%
      lignocaine jelly, surgical dissection of the pterygium, scraping of corneal bed
      with crescent blade, excision of Tenons capsule, harvesting conjunctival limbal
      autograft superiorly, and securing it with respect to limbus and stromal
      orientation with fibrin glue were done. Postoperatively, the patients discomfort
      and pain were evaluated by Wongs pain scoring system. RESULTS: The mean pain
      score was 0.70 +/- 0.97. Only one patient (4.76%) out of the whole series
      experienced pain who rated more than three on the visual analog scale of 5.
      Thirteen patients (61.9%) had pain score of zero, that is, no pain. The surgeons
      evaluation of the technique in terms of surgical ease and complications was
      favorable. There were no dislodged grafts and no cases required suturing. There
      were no cases of infection, significant inflammation, epithelial problems and
      reduction in visual acuity. There was a single case of recurrence (4.76%) five
      months postoperatively which was managed conservatively. CONCLUSIONS: Topical
      anesthesia with lignocaine 2% jelly using fibrin sealant is safe and effective in
      pterygium surgery allowing for short operative times. It results in low pain and
      good aesthetic and functional outcomes.

PMID- 21876590
TI  - Presbyopia and its anatomical and physiological variants.
AB  - AIM: To study the various ocular anatomical and physiological parameters in
      presbyopia. MATERIALS AND METHODS: We studied the various ocular anatomical and
      physiological parameters like corneal curvature (keratometry readings: K1 and
      K2), central corneal thickness (CCT), anterior chamber depth (ACD), lens
      thickness (LT) and axial length (AL) in 100 presbyopic patients between 35 - 55
      years of age. The patients were divided into two age groups: I (35 +/- 44 years)
      and II (45-55 yrs). ACD, AL and LT were measured using an Ascan. CCT was measured
      with ultrasonic pachymetry. RESULTS: The CCT decreased (BE), LT increased and ACD
      decreased (RE) significantly with increasing age (p less than 0.05). There was no
      significant difference in males and females. Nearly 3/4th of the total increase
      in lens thickness was responsible for the decrease in the anterior chamber depth
      and the rest, 1/4th , goes posteriorly. Corneal curvature and AL showed no
      significant change with age. CONCLUSIONS: The mean of CCT decreased significantly
      with advancing age. As age increased, the mean value of lens thickness increased
      and anterior chamber depth decreased. Nearly 3/4th of total increase in LT was
      anteriorly, decreasing the ACD. Corneal curvature and AL has no relation with
      age.

PMID- 21876591
TI  - Cataract surgery in camp patients: a study on visual outcomes.
AB  - AIM: To assess the complications and visual outcomes associated with cataract
      surgery in camp patients operated at a tertiary centre. MATERIALS AND METHODS: In
      a retrospective study, 206 outreach camp patients had undergone cataract
      surgeries with posterior chamber intraocular lens implantation under peribulbar
      anesthesia over a period of 6 months. Post-operative complications on Day 1 were
      graded as per Oxford Cataract Treatment and Evaluation Team (OCTET) definitions.
      One month postoperative complications, best corrected visual acuity and
      refractive errors were assessed. RESULTS: 206 eyes underwent cataract extraction
      with PCIOL implantation. Small incision cataract surgery (SICS) was the commonest
      method (78.6%) used. The most common first post-operative day complication was
      mild iridocyclitis (26.2%). The complications were based on OCTET definitions,
      and showed that 33 % had Grade I and 3.4 % had Grade II complications. The major
      post-operative complication after 4 weeks of surgery was posterior capsular
      opacity. 89.8 % of the eyes had a 4 week-post-operative best corrected visual
      acuity of e+/- 6/24. The commonest refractive error was myopia with against the
      rule astigmatism, seen in 86 out of 150 cases. CONCLUSION: High quality cataract
      surgery with a low rate of intra-operative complications and good visual outcome
      can be attained in camp patients operated in the base hospitals, thus justifying
      more similar screening camps to clear the vast cataract backlog.

PMID- 21876592
TI  - Ocular manifestations in herpes zoster ophthalmicus.
AB  - BACKGROUND: Ocular complications of herpes zoster ophthalmicus (HZO) may lead to
      substantial visual disability, severe post-herpetic neuralgia and rarely fatal
      cerebral complications. AIM: To identify the pattern of ocular manifestation in
      herpes zoster ophthalmicus. MATERIALS AND METHODS: A cross-sectional descriptive
      study was under taken including the clinically diagnosed cases of HZO. All of
      them underwent a complete ophthalmological evaluation. RESULTS: Sixty-eight cases
      of HZO were examined, of which 37 (54.4 %) were male and 31 (45.6%) female. The
      mean age was 48.7 +/- 18.5 years. Most of the patients (64.7 %) were above the
      age of 40 years. 77.94 % of the patients had some form of ocular involvement.
      Pain (77.9 %) was the commonest ocular complaint. In young patients less than 35
      years, HIV was the most common risk factor (19.3 %).Visual status was good in the
      majority (73.5 %) of patients at presentation. Lid and adnexal findings (45.8 %)
      were most common ocular involvement followed by conjunctivitis (41.1 %). Corneal
      complication was seen in 38.2 % of cases, uveitis in 19.1 % and post-herpetic
      neuralgia (PHN) and secondary glaucoma each in 5.8 %. CONCLUSION: Eyelid and
      ocular adnexal involvement is most commonly found in patients with herpes zoster
      ophthalmicus followed by corneal complication and uveitis. There needs to be
      awareness of ocular involvement, which can be sight threatening, among the HZO
      patients and other medical departments and an increased emphasis on regular
      ophthalmic examination.

PMID- 21876593
TI  - Ocular morbidity among primary school children of Dhulikhel, Nepal.
AB  - BACKGROUND: Knowledge of disease pattern in children can help design preventive
      and curative strategies. OBJECTIVE: To study the pattern of ocular morbidity
      among the primary school children. SUBJECTS AND METHODS: All the children of
      randomly-selected five government primary schools of Dhulikhel were included in
      this study. A complete eye examination was done in all children including color
      vision, loupe examination, refraction and Schiotz tonometry. Funduscopy and
      automated perimetry were done in selected children. RESULTS: A total of 466
      primary school children were included in the study, of which 466 children 47
      (10.08 %) had ocular morbidity. Refractive error was the commonest type of ocular
      morbidity in 11 (2.36 %). Hypermetropia was the commonest type of refractive
      error (0.84 %) in contrast to myopia (0.64 %). Conjunctivitis was the second
      common type of ocular morbidity (1.71 %). Glaucoma suspects accounted for 1.28 %,
      xexophthalmia 1.07 %, blephatitis 0.85 %, amblyopia 0.43 %, color blindness 0.43
      %, conjunctival nevus 0.43 %, glaucoma 0.43 %, and strabismus 0.43 %, while
      congenital abnormalities were less common. CONCLUSION: Refractive error is the
      commonest form of ocular morbidity in primary school children.

PMID- 21876594
TI  - Endothelial cell loss after small incision cataract surgery.
AB  - BACKGROUND: The corneal endothelium plays an important role in maintaining the
      dehydrated state and the transparency of the cornea. Some degree of endothelial
      cell loss invariably occurs in all types of cataract surgery but the amount of
      endothelial cell loss varies with the surgical technique. AIM: To evaluate the
      density of the central corneal endothelial cells before and after small incision
      cataract surgery (SICS) with posterior chamber intraocular lens (PC IOL)
      implantation. MATERIALS AND METHODS: A total of 100 eyes of 100 patients
      undergoing SICS with PC IOL were included in the study. Endothelial cell density
      was measured with non-contact specular microscope pre-operatively and post
      operatively on Day 1, Day 7 and at one month. RESULTS: The mean endothelial cell
      count pre-operatively was 2673 +/- 358.85 cells / sq mm while post-operatively at
      1 month it was 2249.77 +/- 354.04 cells / sq mm. CONCLUSION: There is 15.83 %
      reduction in endothelial cell count after SICS with PC IOL implantation, which is
      comparable with other modes of cataract surgery like extra-capsular cataract
      extraction and phacoemulsification.

PMID- 21876595
TI  - Sympathetic ophthalmia: enucleation or evisceration?
AB  - The purpose of this review is to find out the risk of sympathetic ophthalmia
      after evisceration and enucleation particularly in a case of penetrating ocular
      (non-surgical or surgical) injury and to know about the cosmetic outcome of
      evisceration and enucleation. Ophthalmologists around the world, whenever dealing
      with a case of penetrating ocular (non-surgical or surgical) injury, might thus
      be helped in deciding whether to keep the traumatized eye or remove it. And if
      they finally decide to remove it, they will be able to choose between
      evisceration and enucleation for the best cosmetic outcome, and to minimize the
      risk of sympathetic ophthalmia. The results of the review are the following.
      Enucleation is not found to be the best protective measure against development of
      sympathetic ophthalmia, as it was thought to be, since there are ample reports of
      sympathetic ophthalmia occurring not just after evisceration but also after
      enucleation. The cosmetic outcome of evisceration as opposed to enucleation is
      found to be better.

PMID- 21876596
TI  - An unusual case of anisocoria in a child with bleeding aneurysm of posterior
      communicating artery and idiopathic thrombocytopenic purpura (ITP).
AB  - BACKGROUND: ITP can give rise to bleeding episodes in different parts of the body
      including the central nervous system with various systemic manifestations. CASE:
      An eight-year old female child, diagnosed as a case of chronic ITP for last two
      years, developed intense headache and vomiting for a few days before admission.
      This was associated with right sided mid dilated pupil with brisk reaction to
      light. MRI-angiography showed a bleeding aneurysm of posterior communicating
      artery. The features of raised intra cranial tension subsided with conservative
      management but the anisocoria persisted. CONCLUSION: A bleeding aneurysm can
      manifest with anisocoria as a sign of partial third cranial nerve palsy.

PMID- 21876597
TI  - Ophthalmomyiasis in humans.
AB  - BACKGROUND: Ophthalmomyiasis in humans is a rare phenomenon. OBJECTIVES: To
      create awareness among the ophthalmologists regarding larval conjunctivitis.
      CASES: We report two cases of ophthalmomyiasis, which came to a tertiary care
      centre with features of unilateral acute catarrhal conjunctivitis. OBSERVATIONS:
      Fly larvae were detected on slit-lamp examination and removed after immobilizing
      them with topical 4 % lignocaine. Topical antibiotics and steroid drops were
      prescribed for 2 weeks. The samples were identified as Oestrous ovis by the
      entomology department of the Institute of Tropical Medicine, Kolkata. The signs
      and symptoms regressed within 48 hours. CONCLUSION: The ocular myiasis can
      manifest as a unilateral catarrhal conjunctivitis.

PMID- 21876598
TI  - Cavernous lymphangioma of eyelid - a rare case report.
AB  - BACKGROUND: Lymphangioma is a lymphatic malformation, a benign proliferation of
      lymph vessels. CASE: We hereby present a case of eyelid lymphangioma of cavernous
      type in a twelve year old male patient. This is a very uncommon site for this
      type of lymphangioma.

PMID- 21876599
TI  - Ocular surface squamous neoplasia in a young adult - its nature and unusual
      course.
AB  - BACKGROUND: We describe a case of a recurrent ocular surface squamous neoplasia
      (OSSN) in a 37-year-old male with a mass at the infero-temporal quadrant along
      with an isolated primary lesion at the upper nasal quadrant for the last five
      months with a past history of surgical excision 7 years ago for a nodular mass in
      the same eye. The mass showed delayed response to Mitomycin C (MMC) therapy and
      finally developed limbal stem cell deficiency. CASE REPORT: A 37-year-old male
      presented with a five-month history of foreign body sensation and localized
      conjunctival hyperemia and two progressively enlarging bumps over the limbus in
      the left eye. The past history stated a surgical excision , done 7 years ago, for
      a nodular mass cytology. The patient received initial treatment with 0.02% MMC,
      but did not show any improvement even after 3 cycles, but later showed marked
      chemoreduction with 0.04% MMC on two cycles and a complete resolution of the
      neoplasia after two more cycles. Impression cytology at six months revealed no
      abnormality. But at the 10-month follow-up. limbal stem cell deficiency was
      observed. CONCLUSION: While examining, managing and follow-up of a case of OSSN,
      one needs to know the atypical nature and response of the tumour. Long-term
      follow-up in these cases is mandatory.

PMID- 21876600
TI  - Limits and chances in an unfortunate course of recurrent orbital
      rhabdomyosarcoma.
AB  - BACKGROUND: Orbital rhabdomyosarcoma (RMS) in childhood has an excellent survival
      rate after chemotherapy and radiation, and mutilating surgery can often be
      avoided. CASE REPORT: As a rarity we present an unfortunate disease course in a
      child suffering from orbital embryonal RMS which did not enduringly respond to
      multimodal therapy including local excision and exenteration orbitae. After short
      intervals and despite tumor-free margins, orbital RMS recurred twice and led to
      an extended exenteration orbitae including the bony margins. Because of the lack
      of standards for adjuvant therapy in cases of recurrences after exenteration
      orbitae, therapy had to be restricted to a wait- and- see strategy as the only
      chance of tumor control. CONCLUSION: Although survival rates of orbital RMS are
      high, the possibility of recurrence should not be underestimated. In cases of
      refractory RMS, new concepts are needed to offer further chances for survival.

PMID- 21876601
TI  - Cortical blindness and paraplegia following hypoxic ischemic encephalopathy as a
      complication of common krait bite.
AB  - BACKGROUND: A case report of a successful recovery from paraplegia and cortical
      blindness following anti-venom injection for a snake bite by a common krait is
      reported here. CASE: A 14-year old male patient was bitten by a common krait. On
      admission to a tertiary level hospital, he was started with antivenom serum. But
      the patient developed sudden respiratory distress following anaphylactic shock
      and he was kept on ventilation. The patient was discharged with paraplegia with
      loss of vision. He was diagnosed as a case of cortical blindness due to hypoxic
      ischemic encephalopathy. Subsequently, the patient recovered from paraplegia and
      regained visual acuity of 6/60 in both eyes (best corrected). The boy was
      reexamined after four years. CONCLUSION: Evaluation of victims of neurotoxic
      snake bite for early signs of respiratory depression and prompt respiratory
      assistance, even if anti-venom is not available, is most essential as a life
      saving measure.

PMID- 21876602
TI  - Tuberculous dacryoadenitis in a child.
AB  - BACKGROUND: Orbital tuberculosis is rare even in endemic areas. The disease may
      involve soft tissue, lacrimal gland, or the periosteum or bones of the orbital
      wall. CASE: We present an Indian girl, who presented with a slowly growing left
      sided superotemporal orbital mass, with no significant previous medical history.
      The swelling turned to an abscess and burst spontaneously giving rise to a
      discharging sinus. The discharge was negative for any organism on Gram and Giemsa
      staining. A tuberculin skin test was strongly positive. Incisional biopsy showed
      caseating granuloma and Langhan 's giant cells suggestive of tubercular
      aetiology. The patient responded well to tuberculous chemotherapy. CONCLUSION:
      Although tuberculous dacryoadenitis is a very rare manifestation of
      tuberculosis,still the possibility should be entertained in a slowly growing mass
      of the lacrimal gland, especially in developing countries where the prevalence of
      tuberculosis is high.

PMID- 21876603
TI  - Needle capsulorhexis in intumescent white cataract using slow injecting
      viscoelastic device through an anterior chamber maintainer.

PMID- 21876604
TI  - Challenges in the management of corneal ulcer.

PMID- 21876605
TI  - Management of corneal vascularization.

PMID- 21876606
TI  - A need for an awareness campaign about nutrition and hygiene while conducting
      school eye health programs.

PMID- 21876607
TI  - Social organization, population, and land use.
AB  - A new approach to investigation of human influences on the environment identifies
      social organization as an influence independent of population size, affluence,
      and technology. The framework also identifies population events, such as births,
      that influence the environment. The authors use longitudinal, multilevel, mixed
      method measures of local land use changes, population dynamics, and social
      organization to test this framework. These tests reveal that changes in social
      organization are strongly associated with changes in land use independent of
      measures of population size, affluence, and technology. Also, local birth events
      shape local land use changes and key proximate determinants of land use change.

PMID- 21876608
TI  - Exposure to Hazardous Neighborhood Environments in Late Childhood and Anxiety.
AB  - This investigation examined the relationship between living in disordered
      neighborhoods during childhood and anxiety 1 year later. Objective measures of
      neighborhood environment and individual data from a study of mental health in
      suburban children were utilized. Linear regression models were used to assess
      relationships between neighborhood hazard and anxiety. Childhood neighborhood
      disorder was inversely associated with generalized anxiety (beta = 0.037, p<0.01)
      and social phobia (beta = -0.33, p=0.03), but not other forms of anxiety
      including separation anxiety or panic disorder. We suspect that children with
      early exposure to disordered neighborhoods are either desensitized to toxic
      environments or that anxiety is not well specified for this population.

PMID- 21876609
TI  - X-ray diffraction from intact tau aggregates in human brain tissue.
AB  - We describe an instrument to record x-ray diffraction patterns from diseased
      regions of human brain tissue by combining an in-line visible light fluorescence
      microscope with an x-ray diffraction microprobe. We use thiazine red fluorescence
      to specifically label and detect the filamentous tau protein pathology associated
      with Pick's disease, as several labs have done previously. We demonstrate that
      thiazine red-enhanced regions within the tissue show periodic structure in x-ray
      diffraction that is not observed in healthy tissue. One observed periodicity (4.2
      A) is characteristic of cross-beta sheet structure, consistent with previous
      results from powder diffraction studies performed on purified, dried tau protein.

PMID- 21876610
TI  - Serum amyloid alpha in parapneumonic effusions.
AB  - STUDY OBJECTIVES: To assess serum amyloid alpha (SAA) pleural fluid levels in
      parapneumonic effusion (PPE) and to investigate SAA diagnostic performance in PPE
      diagnosis and outcome. METHODS: We studied prospectively 57 consecutive patients
      with PPE (empyema (EMP), complicated (CPE), and uncomplicated parapneumonic
      effusion (UPE)). SAA, CRP, TNF-alpha, IL-1beta, and IL-6 levels were evaluated in
      serum and pleural fluid at baseline. Patients were followed for 6-months to
      detect pleural thickening/loculations. RESULTS: Pleural SAA levels (mg/dL)
      median(IQR) were significantly higher in CPE compared to UPE (P < 0.04); CRP
      levels were higher in EMP and CPE compared to UPE (P < 0.01). There was no
      significant difference between IL-1beta, IL-6, TNF-alpha level in different PPE
      forms. No significant association between SAA levels and 6-month outcome was
      found. At 6-months, patients with no evidence of loculations/thickening had
      significantly higher pleural fluid pH, glucose levels (P = 0.03), lower LDH (P =
      0.005), IL-1beta levels (P = 0.001) compared to patients who presented pleural
      loculations/thickening. CONCLUSIONS: SAA is increased in complicated PPE, and it
      might be useful as a biomarker for UPE and CPE diagnosis. SAA levels did not
      demonstrate considerable diagnostic performance in identifying patients who
      develop pleural thickening/loculations after a PPE.

PMID- 21876611
TI  - Phosphodiesterase type 4D gene polymorphism: association with the response to
      short-acting bronchodilators in paediatric asthma patients.
AB  - Short-acting b2-adrenergic receptor agonists are commonly used bronchodilators
      for symptom relief in asthmatics. The aim of this study was to test whether
      genetic variants in PDE4D gene, a key regulator of b2-adrenoceptor-induced cAMP
      turnover in airway smooth muscle cells, affect the response to short-acting b2
      agonists. Bronchodilator responsiveness was assessed in 133 asthmatic children by
      % change in baseline forced expiratory volume in one second (FEV(1)) after
      administration of albuterol. The analyses were performed in patients with airway
      obstruction (FEV(1)/FVC ratio below 90%, n = 93). FEV(1)  % change adjusted for
      baseline FEV(1) values was significantly different between genotypes of rs1544791
      G/A polymorphism (P = 0.006) and -1345 C/T (rs1504982) promoter variation (P =
      0.03). The association remained significant with inclusion of age, sex, atopy,
      and controller medication into multivariate model (P = 0.004 and P = 0.02,
      resp.). Our work identifies new genetic variants implicated in modulation of
      asthma treatment, one of them (rs1544791) previously associated with asthma
      phenotype.

PMID- 21876612
TI  - Management of fistula-in-ano: an introduction.
AB  - Peri-anal fistulae are a worldwide health problem that can affect any person
      anywhere. Surgical management of these fistulae is not free from risks.
      Recurrence and fecal incontinence are the most common complications after
      surgery. The cumulative personal surgical experience in managing cases with anal
      fistulae is significantly considered as necessary for obtaining better results
      with minimal adverse effects after surgery. The purpose for conducting this
      survey is to facilitate better outcome after surgical interventions in idiopathic
      anal fistulae' cases.

PMID- 21876613
TI  - Anal fistula: intraoperative difficulties and unexpected findings.
AB  - Anal fistula surgery is a commonly performed procedure. The diverse anatomy of
      anal fistulae and their proximity to anal sphincters make accurate preoperative
      diagnosis essential to avoid recurrence and fecal incontinence. Despite the fact
      that proper preoperative diagnosis can be reached in the majority of patients by
      simple clinical examination, endoanal ultrasound or magnetic resonance imaging,
      on many occasions, unexpected findings can be encountered during surgery that can
      make the operation difficult and correct decision-making crucial. In this article
      we discuss the difficulties and unexpected findings that can be encountered
      during anal fistula surgery and how to overcome them.

PMID- 21876614
TI  - Idiopathic fistula-in-ano.
AB  - Fistula-in-ano is the most common form of perineal sepsis. Typically, a fistula
      includes an internal opening, a track, and an external opening. The external
      opening might acutely appear following infection and/or an abscess, or more
      insiduously in a chronic manner. Management includes control of infection,
      assessment of the fistulous track in relation to the anal sphincter muscle, and
      finally, definitive treatment of the fistula. Fistulotomy was the most commonly
      used mode of management, but concerns about post-fistulotomy incontinence
      prompted the use of sphincter preserving techniques such as advancement flaps,
      fibrin glue, collagen fistula plug, ligation of the intersphincteric fistula
      track, and stem cells. Many descriptive and comparative studies have evaluated
      these different techniques with variable outcomes. The lack of consistent
      results, level I evidence, or long-term follow-up, as well as the heterogeneity
      of fistula pathology has prevented a definitive treatment algorithm. This article
      will review the most commonly available modalities and techniques for managing
      idiopathic fistula-in-ano.

PMID- 21876615
TI  - Current management of cryptoglandular fistula-in-ano.
AB  - Fistula-in-ano is a difficult problem that physicians have struggled with for
      centuries. Appropriate treatment is based on 3 central tenets: (1) control of
      sepsis; (2) closure of the fistula; and (3) maintenance of continence. Treatment
      options continue to evolve - as a result, it is important to review old and new
      options on a regular basis to ensure that our patients are provided with up to
      date information and options. This paper will briefly cover some of the
      traditional approaches that have been used as well as some newer promising
      procedures.

PMID- 21876616
TI  - Why do we have so much trouble treating anal fistula?
AB  - Anal fistula is among the most common illnesses affecting man. Medical literature
      dating back to 400 BC has discussed this problem. Various causative factors have
      been proposed throughout the centuries, but it appears that the majority of
      fistulas unrelated to specific causes (e.g. Tuberculosis, Crohn's disease) result
      from infection (abscess) in anal glands extending from the intersphincteric plane
      to various anorectal spaces. The tubular structure of an anal fistula easily
      yields itself to division or unroofing (fistulotomy) or excision (fistulectomy)
      in most cases. The problem with this single, yet effective, treatment plan is
      that depending on the thickness of sphincter muscle the fistula transgresses, the
      patient will have varying degrees of fecal incontinence from minor to total. In
      an attempt to preserve continence, various procedures have been proposed to deal
      with the fistulas. These include: (1) simple drainage (Seton); (2) closure of
      fistula tract using fibrin sealant or anal fistula plug; (3) closure of primary
      opening using endorectal or dermal flaps, and more recently; and (4) ligation of
      intersphincteric fistula tract (LIFT). In most complex cases (i.e. Crohn's
      disease), a proximal fecal diversion offers a measure of symptomatic relief. The
      fact remains that an "ideal" procedure for anal fistula remains elusive. The
      failure of each sphincter-preserving procedure (30%-50% recurrence) often results
      in multiple operations. In essence, the price of preservation of continence at
      all cost is multiple and often different operations, prolonged disability and
      disappointment for the patient and the surgeon. Nevertheless, the surgeon
      treating anal fistulas on an occasional basis should never hesitate in referring
      the patient to a specialist. Conversely, an expert colorectal surgeon must be
      familiar with many different operations in order to selectively tailor an
      operation to the individual patient.

PMID- 21876617
TI  - Why do we have to review our experience in managing cases with idiopathic fistula
      in-ano regularly?
AB  - "Why do we have to review our experience in managing idiopathic fistula-in-ano
      regularly?" In order to answer this apparently simple question, we reviewed our
      clinical and surgical cases and most important relevant literature to find a
      rational and scientific answer. It would appear that whatever method you adopt in
      fistula management, there is a price to pay regarding either rate of recurrence
      (higher with conservative methods) or impairment of continence (higher with
      traditional surgery). Since, at the moment, reliable data to identify a treatment
      as a gold standard in the management of anal fistulas are lacking, the correct
      approach to this condition must consider all the anatomic and clinicopathological
      aspects of the disease; this knowledge joined to an eclectic attitude of the
      surgeon, who should be familiar with different types of treatment, is the only
      guarantee for a satisfactory treatment. As a conclusion, it is worthwhile to
      remember that adequate initial treatment significantly reduces recurrence, which,
      when it occurs, is usually due to failure to recognise the tract and primary
      opening at the initial operation.

PMID- 21876618
TI  - Helicobacter pylori arginase mutant colonizes arginase II knockout mice.
AB  - AIM: To investigate the role of host and bacterial arginases in the colonization
      of mice by Helicobacter pylori (H. pylori). METHODS: H. pylori produces a very
      powerful urease that hydrolyzes urea to carbon dioxide and ammonium, which
      neutralizes acid. Urease is absolutely essential to H. pylori pathogenesis;
      therefore, the urea substrate must be in ample supply for urease to work
      efficiently. The urea substrate is most likely provided by arginase activity,
      which hydrolyzes L-arginine to L-ornithine and urea. Previous work has
      demonstrated that H. pylori arginase is surprisingly not required for
      colonization of wild-type mice. Hence, another in vivo source of the critical
      urea substrate must exist. We hypothesized that the urea source was provided by
      host arginase II, since this enzyme is expressed in the stomach, and H. pylori
      has previously been shown to induce the expression of murine gastric arginase II.
      To test this hypothesis, wild-type and arginase (rocF) mutant H. pylori strain
      SS1 were inoculated into arginase II knockout mice. RESULTS: Surprisingly, both
      the wild-type and rocF mutant bacteria still colonized arginase II knockout mice.
      Moreover, feeding arginase II knockout mice the host arginase inhibitor S-(2
      boronoethyl)-L-cysteine (BEC), while inhibiting > 50% of the host arginase I
      activity in several tissues, did not block the ability of the rocF mutant H.
      pylori to colonize. In contrast, BEC poorly inhibited H. pylori arginase
      activity. CONCLUSION: The in vivo source for the essential urea utilized by H.
      pylori urease is neither bacterial arginase nor host arginase II; instead, either
      residual host arginase I or agmatinase is probably responsible.

PMID- 21876619
TI  - Doxycycline blocks gastric ulcer by regulating matrix metalloproteinase-2
      activity and oxidative stress.
AB  - AIM: To examine the effect of doxycycline on the activity of matrix
      metalloproteinases (MMPs) and oxidative stress in gastric tissues of rats
      following gastric injury. METHODS: Gastric ulcers were generated in rats by
      administration of 70% ethanol, and activity of doxycycline was tested by
      administration 30 min prior to ethanol. Similarly, the effect of doxycycline was
      tested in an indomethacin-induced gastric ulcer model. The activities and
      expression of MMPs were examined by zymography and Western blot analysis.
      RESULTS: Gastric injury in rats as judged by elevated ulcer indices following
      exposure to ulcerogen, either indomethacin or ethanol, was reversed significantly
      by doxycycline. Indomethacin-induced ulcerated gastric tissues exhibited about 12
      fold higher proMMP-9 activity and about 5-fold higher proMMP-3 activity as
      compared to control tissues. Similarly, ethanol induced about 22-fold and about 6
      fold higher proMMP-9 and proMMP-3 activities, respectively, in rat gastric
      tissues. Both proMMP-9 and MMP-3 activities were markedly decreased by
      doxycycline in ulcerogen treated rat gastric tissues. In contrast, the reduced
      MMP-2 activity in ulcerated tissues was increased by doxycycline during ulcer
      prevention. On the other hand, doxycycline inhibited significantly proMMP-9, -2
      and -3 activities in vitro. In addition, doxycycline reduced oxidative load in
      gastric tissues and scavenged H2O2 in vitro. Our results suggest a novel
      regulatory role of doxycycline on MMP-2 activity in addition to inhibitory action
      on MMP-9 and MMP-3 during prevention of gastric ulcers. CONCLUSION: This is the
      first demonstration of dual action of doxycycline, that is, regulation of MMP
      activity and reduction of oxidative stress in arresting gastric injury.

PMID- 21876620
TI  - Immunostaining of PD-1/PD-Ls in liver tissues of patients with hepatitis and
      hepatocellular carcinoma.
AB  - AIM: To investigate the expression of programmed death (PD)-1, PD ligand 1 (PD
      L1) and PD-L2 in liver tissues in the context of chronic hepatitis and
      hepatocellular carcinoma (HCC). METHODS: Liver biopsies and HCC specimens from
      patients were collected and histologically examined. The expression of PD-1, PD
      L1, and PD-L2 in biopsy specimens of chronic hepatitis and HCC specimens was
      evaluated by immunohistochemical staining. The association between the expression
      level of PD-1, PD-L1, and PD-L2 and clinical and pathological variables was
      analyzed statistically. RESULTS: Expression of PD-1 was found in liver
      infiltrating lymphocytes. In contrast, PD-L1 and PD-L2 were expressed in non
      parenchyma liver cells and tumor cells. The expression of PD-L1 was significantly
      correlated with hepatitis B virus infection (1.42 +/- 1.165 vs 0.50 +/- 0.756, P
      = 0.047) and with the stage of HCC (7.50 +/- 2.121 vs 1.75 +/- 1.500 vs 3.00 +/-
      0.001, P = 0.018). PD-1 and PD-Ls were significantly up-regulated in HCC
      specimens (1.40 +/- 1.536 vs 5.71 +/- 4.051, P = 0.000; 1.05 +/- 1.099 vs 4.29 +/
      3.885, P = 0.004; 1.80 +/- 1.473 vs 3.81 +/- 3.400, P = 0.020). CONCLUSION: PD
      L1 may contribute to negative regulation of the immune response in chronic
      hepatitis B. PD-1 and PD-Ls may play a role in immune evasion of tumors.

PMID- 21876621
TI  - Interactions between CagA and smoking in gastric cancer.
AB  - AIM: To examine the interactions between cytotoxin-associated gene (CagA)
      positive Helicobacter pylori infection and smoking in non-cardiac gastric cancer.
      METHODS: A case-control study (257 cases and 514 frequency-matched controls) was
      conducted from September 2008 to July 2010 in Xi'an, China. Cases were newly
      diagnosed, histologically confirmed non-cardiac cancer. Controls were randomly
      selected from similar communities to the cases and were further matched by sex
      and age (+/- 5 years). A face-to-face interview was performed by the
      investigators for each participant. Data were obtained using a standardized
      questionnaire that included questions regarding known or suspected lifestyle and
      environmental risk factors of gastric cancer. A 5 mL sample of fasting venous
      blood was taken. CagA infection was serologically detected by enzyme-linked
      immunosorbent assays. RESULTS: Smoking and CagA infection were statistically
      significant risk factors of non-cardiac cancer. CagA was categorized in tertiles,
      and the odds ratio (OR) was 12.4 (95% CI: 6.1-20.3, P = 0.003) for CagA after
      being adjusted for confounding factors when the high-exposure category was
      compared with the low-exposure category. Smokers had an OR of 5.4 compared with
      subjects who never smoked (95% CI: 2.3-9.0, P = 0.002). The OR of non-cardiac
      cancer was 3.5 (95% CI: 1.8-5.3) for non-smokers with CagA infection, 3.5 (95%
      CI: 1.9-5.1) for smokers without CagA infection, and 8.7 (95% CI: 5.1-11.9) for
      smokers with CagA infection compared with subjects without these risk factors.
      After adjusting for confounding factors, the corresponding ORs of non-cardiac
      cancer were 3.2 (95% CI: 1.5-6.8), 2.7 (95% CI: 1.3-4.9) and 19.5 (95% CI: 10.3
      42.2), respectively. There was a multiplicative interaction between smoking and
      CagA, with a synergistic factor of 2.257 (Z = 2.315, P = 0.021). CONCLUSION:
      These findings support a meaningful interaction between CagA and smoking for the
      risk of gastric cancer which may have implications for its early detection.

PMID- 21876622
TI  - Correlation of fatty liver and abdominal fat distribution using a simple fat
      computed tomography protocol.
AB  - AIM: To evaluate the relationship between hepatic fat infiltration and abdominal
      fat volume by using computed tomography (CT). METHODS: Three hundred and six
      patients who visited our obesity clinic between November 2007 and April 2008
      underwent fat protocol CT scans. The age range of the patients was 19 to 79 years
      and the mean age was 49 years. The male to female ratio was 116:190. Liver and
      spleen attenuation measurements were taken with three regions of interests (ROIs)
      from the liver and two ROIs from the spleen. Hepatic attenuation indices (HAIs)
      were measured as follows: (1) hepatic parenchymal attenuation (CT(LP)); (2) liver
      to spleen attenuation ratio (LS ratio); and (3) difference between hepatic and
      splenic attenuation (LS(dif)). Abdominal fat volume was measured using a 3 mm
      slice CT scan starting at the level of the umbilicus and was automatically
      calculated by a workstation. Abdominal fat was classified into total fat (TF),
      visceral fat (VF), and subcutaneous fat (SF). We used a bivariate correlation
      method to assess the relationship between the three HAIs and TF, VF, and SF.
      RESULTS: There were significant negative correlations between CT(LP), LS ratio,
      and LS(dif) with TF, VF, and SF, respectively. The CT(LP) showed a strong
      negative correlation with TF and VF (r = -0.415 and -0.434, respectively, P <
      0.001). The correlation between CT(LP) and SF was less significant (r = -0.313, P
      < 0.001). CONCLUSION: Fatty infiltration of the liver was correlated with amount
      of abdominal fat and VF was more strongly associated with fatty liver than SF.

PMID- 21876623
TI  - Self-expanding metallic stents drainage for acute proximal colon obstruction.
AB  - AIM: To clarify the usefulness of the self-expanding metallic stents (SEMS) in
      the management of acute proximal colon obstruction due to colon carcinoma before
      curative surgery. METHODS: Eighty-one colon (proximal to spleen flex) carcinoma
      patients (47 males and 34 females, aged 18-94 years, mean = 66.2 years) treated
      between September 2004 and June 2010 for acute colon obstruction were enrolled to
      this study, and their clinical and radiological features were reviewed. After a
      cleaning enema was administered, urgent colonoscopy was performed. Subsequently,
      endoscopic decompression using SEMS placement was attempted. RESULTS: Endoscopic
      decompression using SEMS placement was technically successful in 78 (96.3%) of 81
      patients. Three patients' symptoms could not be relieved after SEMS placement and
      emergent operation was performed 1 d later. The site of obstruction was
      transverse colon in 18 patients, the hepatic flex in 42, and the ascending colon
      in 21. Following adequate cleansing of the colon, patients' abdominal girth was
      decreased from 88 +/- 3 cm before drainage to 72 +/- 6 cm 7 d later, and one
      stage surgery after 8 +/- 1 d (range, 7-10 d) was performed. No anastomotic
      leakage or postoperative stenosis occurred after operation. CONCLUSION: SEMS
      placement is effective and safe in the management of acute proximal colon
      obstruction due to colon carcinoma, and is considered as a bridged method before
      curative surgery.

PMID- 21876624
TI  - Risk factors for predicting early variceal rebleeding after endoscopic variceal
      ligation.
AB  - AIM: To analyze the clinical risk factors for early variceal rebleeding after
      endoscopic variceal ligation (EVL). METHODS: 342 cirrhotic patients with
      esophageal varices who received elective EVL to prevent bleeding or rebleeding at
      our endoscopy center between January 2005 and July 2010. were included in this
      study. The early rebleeding cases after EVL were confirmed by clinical signs or
      endoscopy. A case-control study was performed comparing the patients presenting
      with early rebleeding with those without this complication. RESULTS: The
      incidence of early rebleeding after EVL was 7.60%, and the morbidity of
      rebleeding was 26.9%. Stepwise multivariate logistic regression analysis showed
      that four variables were independent risk factors for early rebleeding: moderate
      to excessive ascites [odds ratio (OR) 62.83, 95% CI: 9.39-420.56, P < 0.001], the
      number of bands placed (OR 17.36, 95% CI: 4.00-75.34, P < 0.001), the extent of
      varices (OR 15.41, 95% CI: 2.84-83.52, P = 0.002) and prothrombin time (PT) > 18
      s (OR 11.35, 95% CI: 1.93-66.70, P = 0.007). CONCLUSION: The early rebleeding
      rate after EVL is mainly affected by the volume of ascites, number of rubber
      bands used to ligate, severity of varices and prolonged PT. Effective measures
      for prevention and treatment should be adopted before and after EVL.

PMID- 21876625
TI  - Hepatitis B virus and hepatocellular carcinoma at the miRNA level.
AB  - AIM: To study Hepatitis B virus (HBV) infection and its association with
      hepatocellular carcinoma (HCC) at the miRNA level. METHODS: Three cellular models
      were used to investigate miRNA expression changes during HBV infection: human
      HepG2 hepatoblastoma cell line as a model without HBV infection; HepG2 cell line
      transfected with a 1.3-fold full-length HBV genome as an acute infection model;
      and HepG2.2.15 cell line, which is derived from HepG2 and stably transfected with
      a complete HBV genome, as a chronic infection model. The miRNA levels were
      examined using microarray technology. To explore the relationship between HBV
      infection and HCC genesis at the miRNA level, we downloaded from national center
      for biotechnology information Gene Expression Omnibus an miRNA expression dataset
      derived from HCC patients, most of whom are HBV carriers. We compared the miRNA
      expression alterations during HBV infection with those in HCC patients, by
      analyzing miRNA expression change profiles statistically. RESULTS: Seventy-seven
      and 48 miRNAs were differentially expressed during acute and chronic HBV
      infection, respectively. Among these miRNAs, 25 were in common, the intersection
      of which was significant under the hypergeometric test (P = 1.3 * 10-11).
      Fourteen miRNAs were observed to change coherently in the acute and chronic
      infections, with one upregulated and 13 downregulated. Eleven showed inverse
      changes during the two phases of infection; downregulated in the acute infection
      and upregulated in the chronic infection. The results imply that common and
      specific mechanisms exist at the miRNA level during acute and chronic HBV
      infection. Besides, comparative analysis of the miRNA expression changes during
      HBV infection with those in HCC indicates that, although miRNA expression changes
      during HBV infection are distinct from those in HCC patients (P < 2.2 * 10-16),
      they exhibited significant correlations (P = 0.0229 for acute infection; P =
      0.0084 for chronic infection). Perturbation of miRNA expression during chronic
      HBV infection was closer to that in HCC patients than that during acute HBV
      infection. This observation implies the contribution of miRNAs to HCC genesis
      from HBV infection. According to their patterns of differential expression in
      acute and chronic HBV infection, as well as in HCC, miRNAs of potential research
      interest could be identified, such as miR-18a/miR-18b, miR-106a, miR-221 and miR
      101. For instance, the gradient expression alteration of miR-221 in the above
      three phases, which is downregulated in acute HBV infection, normally expressed
      in chronic HBV infection, and upregulated in HCC, indicates that it may be a key
      effector for progression of the disease. CONCLUSION: Our analysis provides
      insights into HBV infection and related HCC in relation to miRNAs, and reveals
      some candidate miRNAs for future studies.

PMID- 21876626
TI  - Laparoscopic fenestration vs open fenestration in patients with congenital
      hepatic cysts: a meta-analysis.
AB  - AIM: To determine whether the outcomes of laparoscopic fenestration (LF) were
      superior to open fenestration (OF) for congenital liver cysts. METHODS:
      Comparative studies published between January 1991 and May 2010 on Medline
      (Ovid), Emsco, PubMed, Science Direct; Cochrane Reviews; CNKI; Chinese Biomedical
      Database, VIP and other electronic databases were searched. Randomized controlled
      trials (RCTs) and retrospective case-control studies on the management of
      congenital hepatic cysts were collected according to the pre-determined
      eligibility criteria to establish a literature database. Retrieval was ended in
      May 2010. Meta-analysis was performed using RevMan 5.0 software (Cochrane
      library). RESULTS: Nine retrospective case-control studies involving 657
      patients, comparing LF with OF were included for the final pooled analysis. The
      meta-analysis results showed less operative time [mean difference (MD): -28.76,
      95% CI: -31.03 to 26.49, P < 0.00001]; shorter hospital stay (MD: -3.35, 95% CI: 
      4.46 to -2.24, P < 0.00001); less intraoperative blood loss (MD: -40.18, 95% CI: 
      52.54 to -27.82, P < 0.00001); earlier return to regular diet (MD: -29.19, 95%
      CI: -30.65 to -27.72, P < 0.00001) and activities after operation (MD: -21.85,
      95% CI: -31.18 to -12.51, P < 0.0001) in LF group; there was no significant
      difference between the two groups in postoperative complications (odds ratio:
      0.99, 95% CI: 0.41 to 2.38, P = 0.98) and cysts recurrence rates. CONCLUSION: The
      short-term outcomes of LF for patients with congenital hepatic cysts were
      superior to open approach, but its long-term outcomes should be verified by
      further RCTs and extended follow-up.

PMID- 21876627
TI  - Anchor-wire technique for multiple plastic biliary stents to prevent stent
      dislocation.
AB  - In endoscopic placement of multiple plastic biliary stents (PBSs), we sometimes
      experience proximal dislocation of the first PBS at the time of subsequent PBS
      insertion. We describe the case of a 79-year-old male with obstructive jaundice
      caused by cholangiocarcinoma who needed to receive multiple PBS placements for
      management of cholangitis. Although proximal dislocation of the first PBS was
      observed, we prevented the dislocation via our technique of using guidewire
      inserted from the distal end of the first PBS to the side hole as the anchor
      wire. We could complete this technique only by inserting guidewire through the
      side hole of the first PBS during the process of releasing the first PBS and
      pulling out the guidewire and the inner sheath. It did not matter whether the
      anchor-wire went towards the third portion of the duodenum or the duodenal bulb.
      Here we introduce this "anchor-wire technique", which is useful for the
      prevention of PBS proximal dislocation in placing multiple PBSs.

PMID- 21876628
TI  - Neuropsychological alterations in hepatitis C infection: the role of
      inflammation.
AB  - About 50% of patients with hepatitis C virus (HCV) infection complain of
      neuropsychiatric symptoms, "brain fog", weakness, fatigue, and exhibit some
      degree of quality of life impairment, irrespective of the severity of liver
      disease. Since the first observation of HCV-related cognitive deficits, 10
      studies have been published that have evaluated neuropsychiatric performance in
      patients with HCV infection and different degrees of hepatic impairment.
      Unfortunately, these have often included patients with cirrhosis, patients who
      had acquired the infection through previous intravenous drug misuse, who had a
      history of relatively recent treatment with interferon, or were on psychoactive
      medication. In addition, different neuropsychological batteries and tests that
      explored different cognitive domains were used, which makes the results of the
      studies difficult to compare. Finally, limited information is available on the
      pathogenesis of HCV-related cognitive impairment. Cerebral and/or systemic
      inflammation may be important players but their potential role has not been
      substantiated by experimental data. The present review outlines the available
      evidence of the presence of cognitive impairment in patients with HCV infection,
      with a focus on the potential relationship with cerebral and/or systemic
      inflammation.

PMID- 21876629
TI  - Nutritional recommendations for patients with non-alcoholic fatty liver diseases.
AB  - Fatty liver is the most common liver disease worldwide. Patients with fatty liver
      disease die primarily from cardiovascular disease and not from chronic liver
      diseases. Hyperglycemia and hyperinsulinemia induce lipogenesis, thereby
      increasing the hepatic pool of fatty acids. This pool is also increased by
      increased delivery of fatty acids through the diet or lipolysis in adipose
      tissue. Nutritional consultations and lifestyle modification are important in the
      treatment of non-alcoholic fatty liver disease (NAFLD). Among the dietary
      constituents, combination of vitamin D, vitamin E, and omega-3 fatty acids shows
      promise for the treatment of NAFLD.

PMID- 21876631
TI  - Trend in gastric cancer: 35 years of surgical experience in Japan.
AB  - AIM: To investigate the trend in gastric cancer surgery in the context of rapid
      therapeutic advancement in Japan and East Asia. METHODS: A retrospective analysis
      was performed on 4163 patients who underwent gastric resection for gastric cancer
      with histological confirmation between 1971 and 2007 at the surgical unit in
      Kitasato University Hospital, to determine the trend in gastric cancer requiring
      surgery. RESULTS: Gastric cancer requiring surgical resection increased in our
      hospital, but the incidence adjusted for population was constant during the
      observed period. Interestingly, the ratio of diffuse type/intestinal type gastric
      cancer was unexpectedly unchanged, and that of advanced/early gastric cancer
      (EGC) was, however, markedly reduced, while the actual incidence of potentially
      curative advanced gastric cancer tended to decrease. The incidence of EGC
      requiring surgery tended to increase as a whole, which is consistent with
      increased prevalence of endoscopic surveillance. As a result, overall survival
      and mortality of gastric cancer requiring gastric resection has recently markedly
      improved. CONCLUSION: In Japan, planned interventions may improve surgical
      gastric cancer mortality, but an unexpected trend of persistent existence of
      intestinal type cancer suggests the need for more robust medical intervention.

PMID- 21876630
TI  - Nutrition and physical activity in NAFLD: an overview of the epidemiological
      evidence.
AB  - Nonalcoholic fatty liver disease (NAFLD) has been recognized as a major health
      burden. The high prevalence of NAFLD is probably due to the contemporary
      epidemics of obesity, unhealthy dietary pattern, and sedentary lifestyle. The
      efficacy and safety profile of pharmacotherapy in the treatment of NAFLD remains
      uncertain and obesity is strongly associated with hepatic steatosis; therefore,
      the first line of treatment is lifestyle modification. The usual management of
      NAFLD includes gradual weight reduction and increased physical activity (PA)
      leading to an improvement in serum liver enzymes, reduced hepatic fatty
      infiltration, and, in some cases, a reduced degree of hepatic inflammation and
      fibrosis. Nutrition has been demonstrated to be associated with NAFLD and Non
      alcoholic steatohepatitis (NASH) in both animals and humans, and thus serves as a
      major route of prevention and treatment. However, most human studies are
      observational and retrospective, allowing limited inference about causal
      associations. Large prospective studies and clinical trials are now needed to
      establish a causal relationship. Based on available data, patients should
      optimally achieve a 5%-10% weight reduction. Setting realistic goals is essential
      for long-term successful lifestyle modification and more effort must be devoted
      to informing NAFLD patients of the health benefits of even a modest weight
      reduction. Furthermore, all NAFLD patients, whether obese or of normal weight,
      should be informed that a healthy diet has benefits beyond weight reduction. They
      should be advised to reduce saturated/trans fat and increase polyunsaturated fat,
      with special emphasize on omega-3 fatty acids. They should reduce added sugar to
      its minimum, try to avoid soft drinks containing sugar, including fruit juices
      that contain a lot of fructose, and increase their fiber intake. For the heavy
      meat eaters, especially those of red and processed meats, less meat and increased
      fish intake should be recommended. Minimizing fast food intake will also help
      maintain a healthy diet. PA should be integrated into behavioral therapy in
      NAFLD, as even small gains in PA and fitness may have significant health
      benefits. Potentially therapeutic dietary supplements are vitamin E and vitamin
      D, but both warrant further research. Unbalanced nutrition is not only strongly
      associated with NAFLD, but is also a risk factor that a large portion of the
      population is exposed to. Therefore, it is important to identify dietary patterns
      that will serve as modifiable risk factors for the prevention of NAFLD and its
      complications.

PMID- 21876632
TI  - Function of nonstructural 5A protein of genotype 2a in replication and infection
      of HCV with gene substitution.
AB  - AIM: To explore the function of Nonstructural 5A (NS5A) protein of genotype 2a
      (JFH1) in the replication and infection of hepatitis C virus (HCV). METHODS:
      Intergenotypic chimera FL-J6JFH/J4NS5A was constructed by inserting NS5A gene
      from 1b stain HC-J4 by the overlapping polymerase chain reaction (PCR) method and
      the restriction enzyme reaction. In vitro RNA transcripts of chimera, prototype
      J6JFH and negative control J6JFH1 (GND) were prepared and transfected into Huh
      7.5 cells with liposomes. Immunofluorescence assay (IFA), fluorescence
      quantitative PCR and infection assay were performed to determine the protein
      expression and gene replication in Huh-7.5 cells. RESULTS: The HCV RNA levels in
      FL-J6JFH/J4NS5A chimera RNA transfected cells were significantly lower than the
      wild type at any indicated time point (2.58 +/- 5.97 * 10(6) vs 4.27 +/- 1.72 *
      10(4), P = 0.032). The maximal level of HCV RNA in chimera was 5.6 +/- 1.8 *
      10(4) GE/MUg RNA at day 34 after transfection, while the wild type reached a peak
      level at day 13 which was 126 folds higher (70.65 +/- 14.11 * 10(5) vs 0.56 +/-
      0.90 * 10(5), P = 0.028). HCV proteins could also be detected by IFA in chimera
      transfected cells with an obviously low level. Infection assay showed that FL
      J6JFH/J4NS5A chimera could produce infectious virus particles, ranging from 10 +/
      5 ffu/mL to 78.3 +/- 23.6 ffu/mL, while that of FL-J6JFH1 ranged from 5.8 +/-
      1.5 * 10(2) ffu/mL to 2.5 +/- 1.4 * 10(4) ffu/mL. CONCLUSION: JFH1 NS5A might
      play an important role in the robust replication of J6JFH1. The establishment of
      FL-J6JFH/J4NS5A provided a useful platform for studying the function of other
      proteins of HCV.

PMID- 21876633
TI  - Identification of methylation profile of HOX genes in extrahepatic
      cholangiocarcinoma.
AB  - AIM: To identify methylation profile and novel tumor marker of extrahepatic
      cholangiocarcinoma (CCA) with high throughout microarray. METHODS: Differential
      methylation profile was compared between normal bile duct epithelial cell lines
      and CCA cell lines by methyl-DNA immunoprecipitation (MeDIP) microarray.
      Bisulfite-polymerase chain reaction (BSP) was performed to identify the
      methylated allels of target genes. Expression of target genes was investigated
      before and after the treatment with DNA demethylating agent. Expression of
      candidate genes was also evaluated by immunofluorescence in 30 specimens of CCA
      tissues and 9 normal bile duct tissues. RESULTS: Methylation profile of CCA was
      identified with MeDIP microarray in the respects of different gene functions and
      signaling pathways. Interestingly, 97 genes with hypermethylated CpG islands in
      the promoter region were homeobox genes. The top 5 hypermethylated homeobox genes
      validated by BSP were HOXA2 (94.29%), HOXA5 (95.38%), HOXA11 (91.67%), HOXB4
      (90.56%) and HOXD13 (94.38%). Expression of these genes was reactivated with 5'
      aza-2'-deoxycytidine. Significant expression differences were found between
      normal bile duct and extrahepatic CCA tissues (66.67%-100% vs 3.33%-10%).
      CONCLUSION: HOXA2, HOXA5, HOXA11, HOXB4 and HOXD13 may work as differential
      epigenetic biomarkers between malignant and benign biliary tissues.

PMID- 21876634
TI  - Late SV40 factor: a key mediator of Notch signaling in human
      hepatocarcinogenesis.
AB  - AIM: To investigate the relationship between late SV40 factor (LSF) and Notch
      signaling in the development and progress of hepatocellular carcinoma (HCC).
      METHODS: Liver cancer tissue specimens from 25 patients were analyzed for Notch-1
      and LSF expression by immunohistochemistry. The correlation between expression
      and the biological effects of Notch-1 and LSF were analyzed using genetic and
      pharmacological strategies in HCC cell lines and human normal cell lines,
      including hepatic stellate cells (HSC) and human embryonic kidney epithelial
      cells (HEK). RESULTS: Immunohistochemistry showed that both Notch-1 and LSF were
      significantly upregulated in HCC samples (76%, 19/25, P < 0.0001 and 84%, 21/25,
      P < 0.0001, respectively) compared with non-cancer samples. Activation of Notch-1
      by exogenous transfection of Notch1 intracellular domain increased LSF expression
      in HSC and HEK cells to levels similar to those seen in HepG2 cells. Furthermore,
      blocking Notch-1 activation with a gamma-secretase inhibitor, DAPT, downregulated
      LSF expression in HepG2 cells. Additionally, a biological behavior assay showed
      that forced overexpression of LSF promoted HepG2 cell proliferation and invasion.
      CONCLUSION: LSF is a key mediator of the Notch signaling pathway, suggesting that
      it might be a novel therapeutic target for the treatment of HCC.

PMID- 21876635
TI  - Laparoscopic calibrated total vs partial fundoplication following Heller myotomy
      for oesophageal achalasia.
AB  - AIM: To compare the mid-term outcomes of laparoscopic calibrated Nissen-Rossetti
      fundoplication with Dor fundoplication performed after Heller myotomy for
      oesophageal achalasia. METHODS: Fifty-six patients (26 men, 30 women; mean age
      42.8 +/- 14.7 years) presenting for minimally invasive surgery for oesophageal
      achalasia, were enrolled. All patients underwent laparoscopic Heller myotomy
      followed by a 180 degrees  anterior partial fundoplication in 30 cases (group 1)
      and calibrated Nissen-Rossetti fundoplication in 26 (group 2). Intraoperative
      endoscopy and manometry were used to calibrate the myotomy and fundoplication. A
      6-mo follow-up period with symptomatic evaluation and barium swallow was
      undertaken. One and two years after surgery, the patients underwent symptom
      questionnaires, endoscopy, oesophageal manometry and 24 h oesophago-gastric pH
      monitoring. RESULTS: At the 2-year follow-up, no significant difference in the
      median symptom score was observed between the 2 groups (P = 0.66; Mann-Whitney U
      test). The median percentage time with oesophageal pH < 4 was significantly
      higher in the Dor group compared to the Nissen-Rossetti group (2; range 0.8-10 vs
      0.35; range 0-2) (P < 0.0001; Mann-Whitney U-test). CONCLUSION: Laparoscopic Dor
      and calibrated Nissen-Rossetti fundoplication achieved similar results in the
      resolution of dysphagia. Nissen-Rossetti fundoplication seems to be more
      effective in suppressing oesophageal acid exposure.

PMID- 21876636
TI  - Somatostatin adjunctive therapy for non-variceal upper gastrointestinal
      rebleeding after endoscopic therapy.
AB  - AIM: To evaluate the effect of pantoprazole with a somatostatin adjunct in
      patients with acute non-variceal upper gastrointestinal bleeding (NVUGIB).
      METHODS: We performed a retrospective analysis of a prospective database in a
      tertiary care university hospital. From October 2006 to October 2008, we enrolled
      101 patients with NVUGIB that had a high-risk stigma on endoscopy. Within 24 h of
      hospital admission, all patients underwent endoscopic therapy. After successful
      endoscopic hemostasis, all patients received an 80-mg bolus of pantoprazole
      followed by continuous intravenous infusion (8 mg/h for 72 h). The somatostatin
      adjunct group (n = 49) also received a 250-MUg bolus of somatostatin, followed by
      continuous infusion (250 MUg/h for 72 h). Early rebleeding rates, disappearance
      of endoscopic stigma and risk factors associated with early rebleeding were
      examined. RESULTS: Early rebleeding rates were not significantly different
      between treatment groups (12.2% vs 14.3%, P = 0.766). Disappearance of endoscopic
      stigma on the second endoscopy was not significantly different between treatment
      groups (94.2% vs 95.9%, P = 0.696). Multivariate analysis showed that the
      complete Rockall score was a significant risk factor for early rebleeding (P =
      0.044, OR: 9.080, 95% CI: 1.062-77.595). CONCLUSION: The adjunctive use of
      somatostatin was not superior to pantoprazole monotherapy after successful
      endoscopic hemostasis in patients with NVUGIB.

PMID- 21876637
TI  - Survival and prognostic factors in hepatitis B virus-related acute-on-chronic
      liver failure.
AB  - AIM: To investigate the survival rates and prognostic factors in patients with
      hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS:
      Clinical data in hospitalized patients with HBV-ACLF admitted from 2006 to 2009
      were retrospectively analyzed. Their general conditions and survival were
      analyzed by survival analysis and Cox regression analysis. RESULTS: A total of
      190 patients were included in this study. The overall 1-year survival rate was
      57.6%. Patients not treated with antiviral drugs had a significantly higher
      mortality [relative risk (RR) = 0.609, P = 0.014]. The highest risk of death in
      patients with ACLF was associated with hepatorenal syndrome (HRS) (RR = 2.084, P
      =0.026), while other significant factors were electrolyte disturbances (RR =
      2.062, P = 0.010), and hepatic encephalopathy (HE) (RR = 1.879, P < 0.001).
      CONCLUSION: Antiviral therapy has a strong effect on the prognosis of the
      patients with HBV-ACLF by improving their 1-year survival rate. HRS, electrolyte
      disturbances, and HE also affect patient survival.

PMID- 21876638
TI  - Long-term results of small-diameter proximal splenorenal venous shunt: a
      retrospective study.
AB  - AIM: To investigate recurrent variceal hemorrhage and long-term survival rates of
      patients treated with partial proximal splenorenal venous shunt. METHODS:
      Patients with variceal hemorrhage who were treated with small-diameter proximal
      splenorenal venous shunt in Ruijin Hospital between 1996 and 2009 were included
      in this study. Shunt diameter was determined before operation using Duplex
      Doppler ultrasonography. Peri-operative and long-term results in term of
      rehemorrhage, encephalopathy and mortality were followed up. RESULTS: Ninety
      eight patients with Child A and B variceal hemorrhage received small-diameter
      proximal splenorenal venous shunt with a diameter of 7-10 mm. After operation,
      the patients' mean free portal pressure (P < 0.01) and the flow rate of main
      portal vein (P < 0.01) decreased significantly compared with that before
      operation. The rates of rebleeding and mortality were 6.12% (6 cases) and 2.04%
      (2 cases), respectively. Ninety-one patients were followed up for 7 mo-14 years
      (median, 48.57 mo). Long-term rates of rehemorrhage and encephalopathy were 4.40%
      (4 cases) and 3.30% (3 cases), respectively. Thirteen patients (14.29%) died
      mainly due to progressive hepatic dysfunction. Five- and ten-year survival rates
      were 82.12% and 71.24%, respectively. CONCLUSION: Small-diameter proximal
      splenorenal venous shunt affords protection against variceal rehemorrhage with a
      low occurrence of encephalopathy in patients with normal liver function.

PMID- 21876639
TI  - Three cases of retroperitoneal schwannoma diagnosed by EUS-FNA.
AB  - Schwannomas are peripheral nerve tumors that are typically solitary and benign.
      Their diagnosis is largely based on surgically resected specimens. Recently, a
      number of case reports have indicated that retroperitoneal schwannomas could be
      diagnosed with endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). We
      report the diagnosis of three cases of schwannoma using EUS-FNA. Subjects were
      two males and one female, ages 22, 40, and 46 years, respectively, all of whom
      were symptom-free. Imaging findings showed well-circumscribed round tumors.
      However, as the tumors could not be diagnosed using these findings alone, EUS-FNA
      was performed. Hematoxylin-eosin staining of the resulting tissue fragments
      revealed bland spindle cells with nuclear palisading. There was no disparity in
      nuclear sizes. Immunostaining revealed S-100 protein positivity and all cases
      were diagnosed as schwannomas. Ki-67 indexes were 3%-15%, 2%-3%, and 3%,
      respectively. No case showed any signs of malignancy. As most schwannomas are
      benign tumors and seldom become malignant, we observed these patients without
      therapy. All tumors demonstrated no enlargement and no change in characteristics.
      Schwannomas are almost always benign and can be observed following diagnosis by
      EUS-FNA.

PMID- 21876640
TI  - Is rectal cancer prone to metastasize to lymph nodes than colon cancer?
AB  - The biology of colorectal cancer differs according to its location within the
      large intestine. A report published in a previous issue of World Journal of
      Gastroenterology (November 2010) evaluated the importance of tumor location as a
      risk factor for lymph node metastasis in colorectal cancer, and showed that
      rectal cancer is prone to metastasize to lymph nodes as compared with colon
      cancer. However, in order to conclude that the tumor location is independently
      associated with the occurrence of lymph node metastasis, it is necessary to
      consider a selection bias or other patient- and tumor-related factors carefully.

PMID- 21876641
TI  - Imiquimod 3.75% cream applied daily to treat anogenital warts: combined results
      from women in two randomized, placebo-controlled studies.
AB  - OBJECTIVE: To evaluate if new imiquimod formulations using a shorter treatment
      duration are safe and efficacious to treat anogenital warts. METHODS: In two
      studies 534 women >=12 years of age (mean 33.4) with 2-30 warts (mean 7.9) and
      total wart area >=10 mm(2) (mean 166.3) were randomized (1:2:2) to placebo (106),
      imiquimod 2.5% (212) or 3.75% (216) creams applied once daily until complete
      clearance or a maximum of 8 weeks. RESULTS: For placebo, imiquimod 2.5% and
      3.75%, respectively, complete clearance of all warts was achieved in 14.2%,
      28.3%, and 36.6% of women (intent-to-treat, P = 0.008 imiquimod 2.5%, and P <
      0.001 3.75% versus placebo). Mean changes in wart counts were -10.7%, -50.9%, and
      -63.5% (per-protocol, P < 0.001 each active versus placebo) and safety-related
      discontinuation rates 0.9%, 1.4%, and 2.3%. CONCLUSIONS: Imiquimod 3.75% applied
      daily for up to 8 weeks was well tolerated and superior to placebo in treating
      women with external anogenital warts.

PMID- 21876642
TI  - Prediction of B-cell linear epitopes with a combination of support vector machine
      classification and amino acid propensity identification.
AB  - Epitopes are antigenic determinants that are useful because they induce B-cell
      antibody production and stimulate T-cell activation. Bioinformatics can enable
      rapid, efficient prediction of potential epitopes. Here, we designed a novel B
      cell linear epitope prediction system called LEPS, Linear Epitope Prediction by
      Propensities and Support Vector Machine, that combined physico-chemical
      propensity identification and support vector machine (SVM) classification. We
      tested the LEPS on four datasets: AntiJen, HIV, a newly generated PC, and AHP, a
      combination of these three datasets. Peptides with globally or locally high
      physicochemical propensities were first identified as primitive linear epitope
      (LE) candidates. Then, candidates were classified with the SVM based on the
      unique features of amino acid segments. This reduced the number of predicted
      epitopes and enhanced the positive prediction value (PPV). Compared to four other
      well-known LE prediction systems, the LEPS achieved the highest accuracy
      (72.52%), specificity (84.22%), PPV (32.07%), and Matthews' correlation
      coefficient (10.36%).

PMID- 21876643
TI  - Synergistic effects between phosphorylation of phospholamban and troponin I
      promote relaxation at higher heart rate.
AB  - We hypothesized that the extent of frequency-dependent acceleration of relaxation
      (FDAR) would be less than that of isoproterenol-(ISO-)dependent acceleration of
      relaxation (IDAR) at the same increment of heart rates, and ISO may improve FDAR.
      Cardiac function and phosphorylation of PLB and cTnI were compared in pacing, ISO
      treatment, and combined pacing and ISO treatment in isolated working heart. The
      increase in cardiac output and the degree of relaxation was less in pacing than
      in ISO treatment at the same increment of heart rates. The increasing stimulation
      frequency induced more significant relaxant effect in ISO perfusion than that in
      physiological salt perfusion. The pacing only phosphorylated PLB at Thr17, but
      ISO induced phosphorylation of cTnI and PLB at Ser16 and Thr17. Those results
      suggest that the synergistic effects of PLB and cTnI induce higher degree of
      relaxation which makes a sufficient diastolic filling of the ventricle at higher
      heart rate.

PMID- 21876645
TI  - First-ever Ischemic Stroke after a Flight in a Patient with Prior Poliomyelitis.
AB  - Survivors of poliomyelitis sometimes travel by air with mobility assistance.
      However, prolonged seating during long-haul flights may also possibly produce
      stroke events on polio-inflicted patients. A 48-year-old polio-inflicted male
      suffered a stroke after an extended flight. A two-dimensional echocardiography
      was normal without detected patent foramen ovale or dyskinetic segment. The
      venodynamic variables were all within normal limits. MR Imaging studies revealed
      acute cerebral infarction in the distribution of the right middle cerebral artery
      and posterior watershed area. Hematological examination revealed positive anti
      cardiolipin IgG antibody which might contribute to the risk of thrombosis as an
      underlying condition in addition to immobilization. This is the first
      presentation of ischemic stroke after a flight in a patient with prior
      poliomyelitis. In addition to decompression sickness, economy class stroke
      syndrome and postpoliomyelitis syndrome, the physician should also take other
      coagulation disorders into consideration during the investigation.

PMID- 21876646
TI  - P16 and Ki67 Immunostains Decrease Intra- and Interobserver Variability in the
      Diagnosis and Grading of Anal Intraepithelial Neoplasia (AIN).
AB  - BACKGROUND: Significant variation is reported in the diagnosis of HPV-associated
      AIN. We previously observed that band-like positivity for p16 in >90% of
      contiguous cells coupled with Ki67 positivity in >50% of lesional cells is
      strongly associated with high grade AIN. This study was undertaken to determine
      if addition of p16 and Ki67 immunostaining would reduce inter- and intraobserver
      variability in diagnosis and grading of AIN. DESIGN: H&E stained slides of 60
      anal biopsies were reviewed by three pathologists and consensus diagnoses were
      achieved: 25 negative, 12 low (condyloma and/or AIN I) and 23 high (9 AIN II and
      14 AIN III) grade lesions. The H&E stained slides were diagnosed independently by
      three additional ("participant") pathologists. Several weeks later they re
      examined these slides in conjunction with corresponding p16 and Ki67
      immunostains. RESULTS: Addition of p16 and Ki67 immunostains reduced intra- and
      interobserver variability, improved concurrence with consensus diagnoses and
      reduced two-step differences in diagnosis. Negative and high grade AIN diagnoses
      showed the most improvement in concurrence levels. CONCLUSION: Addition of p16
      and Ki67 immunostains is helpful in the diagnosis and grading of AIN.

PMID- 21876647
TI  - Sclerosing 'mucinous' blue nevus: a clinical simulator of dermatofibroma.

PMID- 21876644
TI  - A window into the heterogeneity of human cerebrospinal fluid Abeta peptides.
AB  - The initiating event in Alzheimer's disease (AD) is an imbalance in the
      production and clearance of amyloid beta (Abeta) peptides leading to the
      formation of neurotoxic brain Abeta assemblies. Cerebrospinal Fluid (CSF), which
      is a continuum of the brain, is an obvious source of markers reflecting central
      neuropathologic features of brain diseases. In this review, we provide an
      overview and update on our current understanding of the pathobiology of human CSF
      Abeta peptides. Specifically, we focused our attention on the heterogeneity of
      the CSF Abeta world discussing (1) basic research studies and what has been
      translated to clinical practice, (2) monomers and other soluble circulating Abeta
      assemblies, and (3) communication modes for Abeta peptides and their
      microenvironment targets. Finally, we suggest that Abeta peptides as well as
      other key signals in the central nervous system (CNS), mainly involved in
      learning and hence plasticity, may have a double-edged sword action on neuron
      survival and function.

PMID- 21876650
TI  - Combined hepatocellular cholangiocarcinomas; analysis of a large database.
AB  - AIM: Combined hepatocellular cholangiocarcinoma (combined tumor) has been
      described as either a variant of hepatoma or a variant of cholangiocarcinoma.
      Prior studies evaluated fewer than 50 patients with combined tumors, precluding
      multivariate analyses. Posited was the notion that analysis of a large database
      would yield more definite answers. METHODS: This study used SEER (Surveillance,
      Epidemiology, and End Results Program of the National Cancer Institute) to
      analyze 282 combined tumors, 2,035 intrahepatic cholangiocarcinomas, and 19,336
      hepatomas between the years 1973-2003. Multinomial logit regression calculated
      point estimates and 95% confidence intervals (c.i.) for relative risk (rr). Cox
      regression calculated point estimates and 95% confidence intervals (c.i.) for
      hazard ratios (h). RESULTS: Men less often had cholangiocarcinomas than they had
      combined tumors (rr = 0.63, c.i. = 0.49-0.81). Hepatomas less often than combined
      tumors presented with distant spread (rr = 0.56, c.i. = 0.43-0.72). Men (rr =
      1.50, c.i. = 1.17-1.93) and patients with a known Asian or Pacific birthplace (rr
      = 2.36, c.i. = 1.56-3.56) more often had hepatomas than they had combined tumors.
      Among patients not known to have an Asian/Pacific birthplace, a diagnosis of
      cholangiocarcinoma (h = 0.72, c.i. = 0.63-0.82) or hepatoma (h = 0.75, c.i. =
      0.66-0.86) provided a better prognosis than did a diagnosis of combined tumor.
      CONCLUSION: Combined tumors differ from hepatomas and cholangiocarcinomas in
      terms of distribution and survival patterns in the population; they should be
      considered neither cholangiocarcinomas nor hepatomas.

PMID- 21876649
TI  - P16/Ki-67 Immunostaining is Useful in Stratification of Atypical Metaplastic
      Epithelium of the Cervix.
AB  - Cervical metaplastic squamous epithelium exhibiting atypia insufficient for a
      diagnosis of cervical intraepithelial neoplasia (CIN) is usually reported as
      "atypical squamous metaplasia" (ASM). Stratification impacts treatment since the
      differential is often between reactive and high grade CIN (CIN II, III).
      Diagnosis with H&E is associated with low intra/interobserver concurrence. P16/Ki
      67 immunostains are helpful to assess cervical biopsies for HPV-associated
      lesions but staining in metaplastic squamous epithelium has received little
      attention. This study aims to establish staining characteristics of metaplastic
      squamous epithelium and determine if p16/Ki-67 is useful in ASM stratification.
      80 cervical biopsies containing morphologically normal and dysplastic squamous
      metaplasia were retrieved to determine the staining characteristics of
      metaplastic epithelium utilizing p16/Ki-67 immunostains. These included 21 benign
      squamous metaplasia (BSM) from benign cervices, 15 BSM present adjacent to
      HPV/CIN lesions, and 44 CIN involving squamous metaplasia. Serial sections with
      controls were stained for p16 and Ki-67 and in-situ hybridization (ISH) for low
      risk (LR) and high-risk (HR) HPV was performed. P16 was recorded as negative,
      spotty, or band-like. Ki-67 was recorded as positive when present in >50% of
      lesional nuclei. Results were correlated with H&E diagnosis. 95% of the BSMs,
      whether from normal cervices or adjacent to HPV/CIN were p16/Ki-67 negative. 81%
      HG CINs involving squamous metaplasia were p16 band/Ki-67 positive. Low grade CIN
      (CIN I) involving metaplastic epithelium showed a broad distribution of p16/Ki-67
      staining patterns. Based on these criteria, 20 ASM were evaluated. 10% of the ASM
      cases were p16 band/Ki-67 positive indicating HG CIN. 60% of the ASMs were p16/Ki
      67 negative indicating reactive change (all with the exception of one case being
      HPV negative). The remaining 30% of the ASM cases showed variable positivity for
      p16 and Ki-67 and could not be stratified into the two categories. Thus p16/Ki-67
      staining is helpful in stratification of ASM as reactive or CIN.

PMID- 21876648
TI  - Tumorigenic effects of tamoxifen on the female genital tract.
AB  - Tamoxifen is widely used for endocrine treatment and breast cancer prevention. It
      acts as both an estrogen antagonist in breast tissue and an estrogen agonist in
      the female lower genital tract. Tamoxifen causes severe gynecologic side effects,
      such as endometrial cancer. This review focuses on the effects of prolonged
      tamoxifen treatment on the human female genital tract and considers its
      tumorigenicity in the gynecologic organs through clinical data analysis.
      Tamoxifen is associated with an increased incidence of benign endometrial lesions
      such as polyps and hyperplasia and a two- to four-fold increased risk of
      endometrial cancer in postmenopausal patients. Moreover, the incidence of
      functional ovarian cysts is significantly high in premenopausal tamoxifen users.
      To prevent tamoxifen from having severe side effects in gynecologic organs,
      frequent gynecological examination should be performed for both premenopausal and
      postmenopausal patients with breast cancer who are treated with this drug.

PMID- 21876651
TI  - Mutation Detection in the Menkes Gene ATP7A Using the Protein Truncation Test.
AB  - Menkes disease (MD) is a rare recessively inherited lethal disorder of copper
      metabolism. The gene ATP7A defective in MD consists of 23 exons and the coding
      region encompasses 4500 bp. About 300 distinct mutations, representing all types,
      have been identified in ATP7A. However all mutations identified so far in the
      exon 2 to exon 7, corresponding to 1869 bp of the coding sequence, result in
      truncated protein products. No missense mutations have been identified in this
      region. As about 30% of the total number of mutations identified are located in
      exon 2 to exon 7, we have designed a protein truncation test (PTT) for rapid
      detecting of mutations in this part of the gene. In order to determine the
      applicability of the test, we analysed RNA obtained from eleven MD patients with
      known mutations in this region. As a truncated product could be identified in all
      the included samples, PTT proves to be a useful technique for rapid detection of
      mutations in the N-terminal part of the ATP7A gene. Furthermore as MD is a X
      linked disease, normally only affecting boys, the risk of false negative results,
      due to nonsense mediated RNA decay, leading to allelic exclusion, can be left out
      of account.

PMID- 21876652
TI  - Squamous differentiation and cytokeratin expression in an osteosarcoma: a case
      report and review of the literature.
AB  - Cytokeratin expression has been documented in a variety of sarcomas including
      synovial sarcomas, epithelioid sarcomas, Ewing's sarcomas and, rarely,
      osteosarcomas. In osteosarcomas immunohistochemically shown to expression
      cytokeratins, a component of epithelioid cells is generally present. These
      epithelioid cytokeratin positive cells raise the possibility of metastatic
      disease with prognostic and therapeutic implications differing from primary
      osteosarcoma. The cytokeratin-expressing cells of the cases reported in the
      literature have not shown definitive squamous differentiation with keratin pearl
      formation. We report a case of osteosarcoma in which islands of malignant
      squamous cells were present showing keratin pearl formation and expression of
      cytokeratins.

PMID- 21876654
TI  - Histological Changes on Liver Glycogen Storage in Mice (Mus musculus) Caused by
      Unbalanced Diets.
AB  - Weight-losing diets have appealed to people who want to lose weight in the short
      term. They usually apply high-protein (HP) diets (like Atkin's, Stillman's,
      Scarsdale) which they practice for 2 weeks or so. Unfortunately, these people who
      have rapid weight loss return to their old habits and quickly regain the weight
      lost. We have shown in previous work that actually these weight losses have been
      associated with body fluids, protein and glycogen storage. In our study, we
      examined the effect of unbalanced diet-related to an HP diet- on liver glycogen
      storage.For this study 40 Swiss albino mice consisting of two groups were used.
      The first group (HPSD) was fed with 25% HP for fifteen days and then were fed
      standard meals for the remaining 15 days; the other group was fed with standard
      meals throughout. The two groups were fed their respective diets for 30 days. At
      the end of 15th, 20th, 25th and 30th days 5 from each group were killed with
      cervical dislocation. The livers were removed perfused and then fixated.There
      were major differences in weight between the first and the fifteenth days. We
      detected remarkable increase in the weight gain of mice in the remaining 15 days.
      Glycogen storage was significantly reduced in HPSD (15) stained with PAS. In the
      others 20th, 25th and 30th days abnormally dense glycogen deposits were observed.
      Vacuoles in the hepatocyte cytoplasm, brownish deposits within hepatocytes, wide
      sinusoids, macrovesiculler steatosis structures and hydropic degeneration were
      observed in PAS and H&E stained HPSD group.As a result for the HPSD group a
      significant decrement in glycogen storage at the 15th day and also an
      accumulation of excessive amounts of glycogen deposits in mice liver was observed
      in the normal feeding phase.

PMID- 21876653
TI  - Combination of immunohistochemistry and ploidy analysis to assist
      histopathological diagnosis of molar diseases.
AB  - BACKGROUND: Differential diagnosis between hydropic abortion, partial mole and
      complete mole is still a challenge for pathologists but really important for
      patient management. MATERIAL AND METHOD: In this study, we have evaluated 111
      products of conception from the first trimester. Histological analysis was made
      according to the main diagnostic histopathological features described in the
      literature and the cases were categorized in hydropic abortus (HA), partial mole
      (PM) and complete mole (CM). Immunohistochemistry was performed using monoclonal
      antibody against p57(kip) protein a putative paternally imprinted inhibitor gene
      and DNA ploidy was analysed in all cases by image cytometry. RESULTS: All 23 HAs
      presented a diploid DNA content and were p57(kip2) positive. From the 28 CMs, 12
      cases (43%) were diploid and 16 cases (57%) were tetraploid but no expression of
      p57(kip2) was found with positive internal controls. From the 60 PMs, 58 cases
      were positive for p57(kip2) expression and 53 cases (88%) were triploid, 6 cases
      (10%) tetraploid and 1 case (2%) diploid. CONCLUSION: This study on 111 cases of
      early pregnancies confirms the usefulness of immunohistochemistry and cytometry
      but demonstrates the importance of the combination of both techniques to assist
      histology for the best reliable diagnosis.

PMID- 21876655
TI  - Histopathologic review of previously negative prostatic core needle biopsies
      following a new diagnosis of adenocarcinoma of the prostate by core needle
      biopsies: implications for quality assurance programs.
AB  - Programs for quality assurance are increasingly important in surgical pathology.
      Many quality assurance (QA) techniques for surgical pathology were adopted from
      procedures introduced in cytopathology. Surgical pathology specimens have
      diminished in size such that the majority of diagnostic biopsies of prostatic
      lesions are now core needle biopsies. These specimens raise issues similar to
      those of cytology specimens, including concerns regarding adequacy and the
      representative nature of the biopsy. Due to sample size, some neoplasms may not
      be diagnosed on initial biopsy, raising concerns regarding false negative
      results. Cytopathologists have instituted QA procedures including review of all
      previously negative slides received within five years prior to the new diagnosis
      of high grade squamous intraepithelial lesion or gynecologic malignancy. No such
      requirement exists in surgical pathology for review of core biopsies.The
      Department of Pathology at the University of Utah instituted a QA policy
      requiring review of prior negative prostatic needle biopsies following a new
      diagnosis of prostatic adenocarcinoma. We reviewed five years of QA records of
      prostate needle biopsy review. During this time, nine hundred and fifty-eight
      core biopsy sets were performed. Two hundred and ninety-five of these contained
      at least one biopsy with a diagnosis of adenocarcinoma. Two hundred and eight
      patients had a prior set of prostatic needle biopsies with a diagnosis of
      adenocarcinoma. The remaining 87 had prior biopsies with either a diagnosis of
      prostatic intraepithelial neoplasia (23), small atypical acinar proliferation
      (21) or no evidence of malignancy (43). QA review of these 87 cases revealed two
      biopsies which revealed foci of adenocarcinoma. Both had been initially diagnosed
      as no evidence of malignancy. The false negative rate for core biopsy was 0.68%.
      In an additional twenty-one cases, microscopic foci of atypical small acinar
      proliferations were found in core biopsies antedating the positive core biopsy
      (7.1%).

PMID- 21876656
TI  - Commonality between diabetes and Alzheimer's disease and a new strategy for the
      therapy.

PMID- 21876657
TI  - Progesterone and Estrogen Receptors in Neurofibromas of Patients with NF1.
AB  - Neurofibromatosis type 1 (NF1) or von Recklinghausen disease is a genetic
      disorder affecting the growth of cells in nervous system. One of the most
      remarkable characteristics of this disease is the development of benign tumors of
      the nervous system (neurofibromas).The purpose of this study was to test tissue
      samples taken from neurofibromas and plexiform neurofibromas of NF1 patients for
      the presence of estrogen and progesterone receptors. We used previously collected
      samples from patients registered in the database of the Centro Nacional de
      Neurofibromatose (CNNF-Brazil). Samples from twenty-five patients in the database
      presenting plexiform neurofibromas (N1 group) and 25 samples from the same
      database from patients presenting neurofibromas (N2 group) were tested.We
      observed positive staining for progesterone receptors in 13 of the neurofibroma
      samples and 19 of the plexiform neurofibroma samples. Among the neurofibroma
      samples, we observed one sample with positive estrogen receptor staining, but
      none of the plexiform neurofibroma samples showed positive staining. We suggest
      further studies to investigate in greater depth possible hormonal influences on
      the development and growth of neurofibromas and plexiform neurofibromas in NF1.

PMID- 21876658
TI  - The pathogenesis of autism.
AB  - Autism is well known as a complex developmental disorder with a seemingly
      confusing and uncertain pathogenesis. The definitive mechanisms that promote
      autism are poorly understood and mostly unknown, yet available theories do appear
      to focus on the disruption of normal cerebral development and its subsequent
      implications on the functional brain unit. This mini-review aims solely to
      discuss and evaluate the most prominent current theories regarding the
      pathogenesis of autism. The main conclusion is that although there is not a clear
      pathway of mechanisms directed towards a simple pathogenesis and an established
      link to autism on the symptomatic level; there are however several important
      theories (neural connectivity, neural migration, excitatory-inhibitory neural
      activity, dendritic morphology, neuroimmune; calcium signalling and mirror
      neurone) which appear to offer an explanation to how autism develops. It seems
      probable that autism's neurodevelopmental defect is 'multi-domain' in origin
      (rather than a single anomaly) and is hence distributed across numerous levels of
      study (genetic, immunopathogenic, etc.). A more definitive understanding of the
      pathogenesis could facilitate the development of better treatments for this
      complex psychiatric disorder.

PMID- 21876660
TI  - Fractionation of volatile constituents from curcuma rhizome by preparative gas
      chromatography.
AB  - A preparative gas chromatography (pGC) method was developed for the separation of
      volatile components from the methanol extract of Curcuma rhizome. The compounds
      were separated on a stainless steel column packed with 10% OV-101 (3 m * 6 mm,
      i.d.), and then, the effluent was split into two gas flows. One percent of the
      effluent passed to the flame ionization detector (FID) for detection and the
      remaining 99% were directed to the fraction collector. Five volatile compounds
      were collected from the methanol extract of Curcuma rhizome (5 g/mL) after 83
      single injections (20 uL) with the yield of 5.1-46.2 mg. Furthermore, the
      structures of the obtained compounds were identified as beta-elemene, curzerene,
      curzerenone, curcumenol, and curcumenone by MS and NMR spectra, respectively.

PMID- 21876659
TI  - Pathology-dependent histological changes of the left stellate Ganglia: a
      cadaveric study.
AB  - Sympathetic hyperinnervation due to nerve sprouting generated by the left
      stellate ganglion has been noted following cardiopulmonary disease processes.
      Sympathetic hyperinnervation seems to be limited to cardiopulmonary diseases in
      the experimental and clinical settings. However, histological changes of the left
      stellate ganglion following cardiopulmonary diseases in humans have vet to be
      observed. This study intends to investigate the histological changes of cadaveric
      sympathetic nervous tissue of left stellate ganglia (n = 32) and their
      relationship to noted pathology. Our study found fibrotic changes of the left
      stellate ganglion are not significantly dependent upon pathological processes,
      however, changes in the number of nerve cell bodies seems to be pathology
      dependent. A relationship between respiratory (mean = 33.3; P = 0.023) and
      cardiovascular pathologies (mean = 29.6; P = 0.199) and an increase in nerve cell
      bodies of the left stellate ganglion was noted when compared to other pathologies
      (mean = 25.7). The link between cardiopulmonary disease and sympathetic
      hyperinnervation may be the increase in the number of nerve cell bodies of the
      left stellate ganglion. Our results are clinically significant considering
      sympathetic hyperinnervation is associated with arrythmogenesis and an increase
      in morbidity and mortality in patients with pulmonary disease. Such findings may
      warrant investigation into the use of ganglion blockade in cardiopulmonary
      diseases.

PMID- 21876661
TI  - A neurocomputational model of stimulus-specific adaptation to oddball and Markov
      sequences.
AB  - Stimulus-specific adaptation (SSA) occurs when the spike rate of a neuron
      decreases with repetitions of the same stimulus, but recovers when a different
      stimulus is presented. It has been suggested that SSA in single auditory neurons
      may provide information to change detection mechanisms evident at other scales
      (e.g., mismatch negativity in the event related potential), and participate in
      the control of attention and the formation of auditory streams. This article
      presents a spiking-neuron model that accounts for SSA in terms of the convergence
      of depressing synapses that convey feature-specific inputs. The model is
      anatomically plausible, comprising just a few homogeneously connected
      populations, and does not require organised feature maps. The model is calibrated
      to match the SSA measured in the cortex of the awake rat, as reported in one
      study. The effect of frequency separation, deviant probability, repetition rate
      and duration upon SSA are investigated. With the same parameter set, the model
      generates responses consistent with a wide range of published data obtained in
      other auditory regions using other stimulus configurations, such as block,
      sequential and random stimuli. A new stimulus paradigm is introduced, which
      generalises the oddball concept to Markov chains, allowing the experimenter to
      vary the tone probabilities and the rate of switching independently. The model
      predicts greater SSA for higher rates of switching. Finally, the issue of whether
      rarity or novelty elicits SSA is addressed by comparing the responses of the
      model to deviants in the context of a sequence of a single standard or many
      standards. The results support the view that synaptic adaptation alone can
      explain almost all aspects of SSA reported to date, including its purported
      novelty component, and that non-trivial networks of depressing synapses can
      intensify this novelty response.

PMID- 21876662
TI  - Binding free energy landscape of domain-peptide interactions.
AB  - Peptide recognition domains (PRDs) are ubiquitous protein domains which mediate
      large numbers of protein interactions in the cell. How these PRDs are able to
      recognize peptide sequences in a rapid and specific manner is incompletely
      understood. We explore the peptide binding process of PDZ domains, a large PRD
      family, from an equilibrium perspective using an all-atom Monte Carlo (MC)
      approach. Our focus is two different PDZ domains representing two major PDZ
      classes, I and II. For both domains, a binding free energy surface with a strong
      bias toward the native bound state is found. Moreover, both domains exhibit a
      binding process in which the peptides are mostly either bound at the PDZ binding
      pocket or else interact little with the domain surface. Consistent with this,
      various binding observables show a temperature dependence well described by a
      simple two-state model. We also find important differences in the details between
      the two domains. While both domains exhibit well-defined binding free energy
      barriers, the class I barrier is significantly weaker than the one for class II.
      To probe this issue further, we apply our method to a PDZ domain with dual
      specificity for class I and II peptides, and find an analogous difference in
      their binding free energy barriers. Lastly, we perform a large number of fixed
      temperature MC kinetics trajectories under binding conditions. These trajectories
      reveal significantly slower binding dynamics for the class II domain relative to
      class I. Our combined results are consistent with a binding mechanism in which
      the peptide C terminal residue binds in an initial, rate-limiting step.

PMID- 21876663
TI  - Effective stimuli for constructing reliable neuron models.
AB  - The rich dynamical nature of neurons poses major conceptual and technical
      challenges for unraveling their nonlinear membrane properties. Traditionally,
      various current waveforms have been injected at the soma to probe neuron
      dynamics, but the rationale for selecting specific stimuli has never been
      rigorously justified. The present experimental and theoretical study proposes a
      novel framework, inspired by learning theory, for objectively selecting the
      stimuli that best unravel the neuron's dynamics. The efficacy of stimuli is
      assessed in terms of their ability to constrain the parameter space of
      biophysically detailed conductance-based models that faithfully replicate the
      neuron's dynamics as attested by their ability to generalize well to the neuron's
      response to novel experimental stimuli. We used this framework to evaluate a
      variety of stimuli in different types of cortical neurons, ages and animals.
      Despite their simplicity, a set of stimuli consisting of step and ramp current
      pulses outperforms synaptic-like noisy stimuli in revealing the dynamics of these
      neurons. The general framework that we propose paves a new way for defining,
      evaluating and standardizing effective electrical probing of neurons and will
      thus lay the foundation for a much deeper understanding of the electrical nature
      of these highly sophisticated and non-linear devices and of the neuronal networks
      that they compose.

PMID- 21876664
TI  - Evolutionary accessibility of mutational pathways.
AB  - Functional effects of different mutations are known to combine to the total
      effect in highly nontrivial ways. For the trait under evolutionary selection
      ('fitness'), measured values over all possible combinations of a set of mutations
      yield a fitness landscape that determines which mutational states can be reached
      from a given initial genotype. Understanding the accessibility properties of
      fitness landscapes is conceptually important in answering questions about the
      predictability and repeatability of evolutionary adaptation. Here we
      theoretically investigate accessibility of the globally optimal state on a wide
      variety of model landscapes, including landscapes with tunable ruggedness as well
      as neutral 'holey' landscapes. We define a mutational pathway to be accessible if
      it contains the minimal number of mutations required to reach the target
      genotype, and if fitness increases in each mutational step. Under this definition
      accessibility is high, in the sense that at least one accessible pathway exists
      with a substantial probability that approaches unity as the dimensionality of the
      fitness landscape (set by the number of mutational loci) becomes large. At the
      same time the number of alternative accessible pathways grows without bounds. We
      test the model predictions against an empirical 8-locus fitness landscape
      obtained for the filamentous fungus Aspergillus niger. By analyzing subgraphs of
      the full landscape containing different subsets of mutations, we are able to
      probe the mutational distance scale in the empirical data. The predicted effect
      of high accessibility is supported by the empirical data and is very robust,
      which we argue reflects the generic topology of sequence spaces. Together with
      the restrictive assumptions that lie in our definition of accessibility, this
      implies that the globally optimal configuration should be accessible to genome
      wide evolution, but the repeatability of evolutionary trajectories is limited
      owing to the presence of a large number of alternative mutational pathways.

PMID- 21876665
TI  - Statistical inference for multi-pathogen systems.
AB  - There is growing interest in understanding the nature and consequences of
      interactions among infectious agents. Pathogen interactions can be operational at
      different scales, either within a co-infected host or in host populations where
      they co-circulate, and can be either cooperative or competitive. The detection of
      interactions among pathogens has typically involved the study of synchrony in the
      oscillations of the protagonists, but as we show here, phase association provides
      an unreliable dynamical fingerprint for this task. We assess the capacity of a
      likelihood-based inference framework to accurately detect and quantify the
      presence and nature of pathogen interactions on the basis of realistic amounts
      and kinds of simulated data. We show that when epidemiological and demographic
      processes are well understood, noisy time series data can contain sufficient
      information to allow correct inference of interactions in multi-pathogen systems.
      The inference power is dependent on the strength and time-course of the
      underlying mechanism: stronger and longer-lasting interactions are more easily
      and more precisely quantified. We examine the limitations of our approach to
      stochastic temporal variation, under-reporting, and over-aggregation of data. We
      propose that likelihood shows promise as a basis for detection and quantification
      of the effects of pathogen interactions and the determination of their
      (competitive or cooperative) nature on the basis of population-level time-series
      data.

PMID- 21876666
TI  - Essential requirements for robust signaling in Hfq dependent small RNA networks.
AB  - Bacteria possess networks of small RNAs (sRNAs) that are important for modulating
      gene expression. At the center of many of these sRNA networks is the Hfq protein.
      Hfq's role is to quickly match cognate sRNAs and target mRNAs from among a large
      number of possible combinations and anneal them to form duplexes. Here we show
      using a kinetic model that Hfq can efficiently and robustly achieve this
      difficult task by minimizing the sequestration of sRNAs and target mRNAs in Hfq
      complexes. This sequestration can be reduced by two non-mutually exclusive
      kinetic mechanisms. The first mechanism involves heterotropic cooperativity
      (where sRNA and target mRNA binding to Hfq is influenced by other RNAs bound to
      Hfq); this cooperativity can selectively decrease singly-bound Hfq complexes and
      ternary complexes with non-cognate sRNA-target mRNA pairs while increasing
      cognate ternary complexes. The second mechanism relies on frequent RNA
      dissociation enabling the rapid cycling of sRNAs and target mRNAs among different
      Hfq complexes; this increases the probability the cognate ternary complex forms
      before the sRNAs and target mRNAs degrade. We further demonstrate that the
      performance of sRNAs in isolation is not predictive of their performance within a
      network. These findings highlight the importance of experimentally characterizing
      duplex formation in physiologically relevant contexts with multiple RNAs
      competing for Hfq. The model will provide a valuable framework for guiding and
      interpreting these experiments.

PMID- 21876667
TI  - Spatial stereoresolution for depth corrugations may be set in primary visual
      cortex.
AB  - Stereo "3D" depth perception requires the visual system to extract binocular
      disparities between the two eyes' images. Several current models of this process,
      based on the known physiology of primary visual cortex (V1), do this by computing
      a piecewise-frontoparallel local cross-correlation between the left and right
      eye's images. The size of the "window" within which detectors examine the local
      cross-correlation corresponds to the receptive field size of V1 neurons. This
      basic model has successfully captured many aspects of human depth perception. In
      particular, it accounts for the low human stereoresolution for sinusoidal depth
      corrugations, suggesting that the limit on stereoresolution may be set in primary
      visual cortex. An important feature of the model, reflecting a key property of V1
      neurons, is that the initial disparity encoding is performed by detectors tuned
      to locally uniform patches of disparity. Such detectors respond better to square
      wave depth corrugations, since these are locally flat, than to sinusoidal
      corrugations which are slanted almost everywhere. Consequently, for any given
      window size, current models predict better performance for square-wave disparity
      corrugations than for sine-wave corrugations at high amplitudes. We have recently
      shown that this prediction is not borne out: humans perform no better with square
      wave than with sine-wave corrugations, even at high amplitudes. The failure of
      this prediction raised the question of whether stereoresolution may actually be
      set at later stages of cortical processing, perhaps involving neurons tuned to
      disparity slant or curvature. Here we extend the local cross-correlation model to
      include existing physiological and psychophysical evidence indicating that larger
      disparities are detected by neurons with larger receptive fields (a
      size/disparity correlation). We show that this simple modification succeeds in
      reconciling the model with human results, confirming that stereoresolution for
      disparity gratings may indeed be limited by the size of receptive fields in
      primary visual cortex.

PMID- 21876668
TI  - Coordination of KSHV latent and lytic gene control by CTCF-cohesin mediated
      chromosome conformation.
AB  - Herpesvirus persistence requires a dynamic balance between latent and lytic cycle
      gene expression, but how this balance is maintained remains enigmatic. We have
      previously shown that the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) major
      latency transcripts encoding LANA, vCyclin, vFLIP, v-miRNAs, and Kaposin are
      regulated, in part, by a chromatin organizing element that binds CTCF and
      cohesins. Using viral genome-wide chromatin conformation capture (3C) methods, we
      now show that KSHV latency control region is physically linked to the promoter
      regulatory region for ORF50, which encodes the KSHV immediate early protein RTA.
      Other linkages were also observed, including an interaction between the 5' and 3'
      end of the latency transcription cluster. Mutation of the CTCF-cohesin binding
      site reduced or eliminated the chromatin conformation linkages, and deregulated
      viral transcription and genome copy number control. siRNA depletion of CTCF or
      cohesin subunits also disrupted chromosomal linkages and deregulated viral latent
      and lytic gene transcription. Furthermore, the linkage between the latent and
      lytic control region was subject to cell cycle fluctuation and disrupted during
      lytic cycle reactivation, suggesting that these interactions are dynamic and
      regulatory. Our findings indicate that KSHV genomes are organized into chromatin
      loops mediated by CTCF and cohesin interactions, and that these inter-chromosomal
      linkages coordinate latent and lytic gene control.

PMID- 21876669
TI  - Phenotypic screens, chemical genomics, and antimalarial lead discovery.

PMID- 21876670
TI  - Activation of HIV transcription by the viral Tat protein requires a demethylation
      step mediated by lysine-specific demethylase 1 (LSD1/KDM1).
AB  - The essential transactivator function of the HIV Tat protein is regulated by
      multiple posttranslational modifications. Although individual modifications are
      well characterized, their crosstalk and dynamics of occurrence during the HIV
      transcription cycle remain unclear.We examine interactions between two critical
      modifications within the RNA-binding domain of Tat: monomethylation of lysine 51
      (K51) mediated by Set7/9/KMT7, an early event in the Tat transactivation cycle
      that strengthens the interaction of Tat with TAR RNA, and acetylation of lysine
      50 (K50) mediated by p300/KAT3B, a later process that dissociates the complex
      formed by Tat, TAR RNA and the cyclin T1 subunit of the positive transcription
      elongation factor b (P-TEFb). We find K51 monomethylation inhibited in synthetic
      Tat peptides carrying an acetyl group at K50 while acetylation can occur in
      methylated peptides, albeit at a reduced rate. To examine whether Tat is subject
      to sequential monomethylation and acetylation in cells, we performed mass
      spectrometry on immunoprecipitated Tat proteins and generated new modification
      specific Tat antibodies against monomethylated/acetylated Tat. No bimodified Tat
      protein was detected in cells pointing to a demethylation step during the Tat
      transactivation cycle. We identify lysine-specific demethylase 1 (LSD1/KDM1) as a
      Tat K51-specific demethylase, which is required for the activation of HIV
      transcription in latently infected T cells. LSD1/KDM1 and its cofactor CoREST
      associates with the HIV promoter in vivo and activate Tat transcriptional
      activity in a K51-dependent manner. In addition, small hairpin RNAs directed
      against LSD1/KDM1 or inhibition of its activity with the monoamine oxidase
      inhibitor phenelzine suppresses the activation of HIV transcription in latently
      infected T cells.Our data support the model that a LSD1/KDM1/CoREST complex,
      normally known as a transcriptional suppressor, acts as a novel activator of HIV
      transcription through demethylation of K51 in Tat. Small molecule inhibitors of
      LSD1/KDM1 show therapeutic promise by enforcing HIV latency in infected T cells.

PMID- 21876671
TI  - Anti-apoptotic machinery protects the necrotrophic fungus Botrytis cinerea from
      host-induced apoptotic-like cell death during plant infection.
AB  - Necrotrophic fungi are unable to occupy living plant cells. How such pathogens
      survive first contact with living host tissue and initiate infection is therefore
      unclear. Here, we show that the necrotrophic grey mold fungus Botrytis cinerea
      undergoes massive apoptotic-like programmed cell death (PCD) following
      germination on the host plant. Manipulation of an anti-apoptotic gene BcBIR1
      modified fungal response to PCD-inducing conditions. As a consequence, strains
      with reduced sensitivity to PCD were hyper virulent, while strains in which PCD
      was over-stimulated showed reduced pathogenicity. Similarly, reduced levels of
      PCD in the fungus were recorded following infection of Arabidopsis mutants that
      show enhanced susceptibility to B. cinerea. When considered together, these
      results suggest that Botrytis PCD machinery is targeted by plant defense
      molecules, and that the fungal anti-apoptotic machinery is essential for
      overcoming this host-induced PCD and hence, for establishment of infection. As
      such, fungal PCD machinery represents a novel target for fungicides and
      antifungal drugs.

PMID- 21876673
TI  - B chromosomes have a functional effect on female sex determination in Lake
      Victoria cichlid fishes.
AB  - The endemic cichlid fishes in Lake Victoria are a model system for speciation
      through adaptive radiation. Although the evolution of the sex-determination
      system may also play a role in speciation, little is known about the sex
      determination system of Lake Victoria cichlids. To understand the evolution of
      the sex-determination system in these fish, we performed cytogenetic analysis in
      11 cichlid species from Lake Victoria. B chromosomes, which are present in
      addition to standard chromosomes, were found at a high prevalence rate (85%) in
      these cichlids. In one species, B chromosomes were female-specific. Cross
      breeding using females with and without the B chromosomes demonstrated that the
      presence of the B chromosomes leads to a female-biased sex ratio in this species.
      Although B chromosomes were believed to be selfish genetic elements with little
      effect on phenotype and to lack protein-coding genes, the present study provides
      evidence that B chromosomes have a functional effect on female sex determination.
      FISH analysis using a BAC clone containing B chromosome DNA suggested that the B
      chromosomes are derived from sex chromosomes. Determination of the nucleotide
      sequences of this clone (104.5 kb) revealed the presence of several protein
      coding genes in the B chromosome, suggesting that B chromosomes have the
      potential to contain functional genes. Because some sex chromosomes in amphibians
      and arthropods are thought to be derived from B chromosomes, the B chromosomes in
      Lake Victoria cichlids may represent an evolutionary transition toward the
      generation of sex chromosomes.

PMID- 21876672
TI  - Salmonella bongori provides insights into the evolution of the Salmonellae.
AB  - The genus Salmonella contains two species, S. bongori and S. enterica. Compared
      to the well-studied S. enterica there is a marked lack of information regarding
      the genetic makeup and diversity of S. bongori. S. bongori has been found
      predominantly associated with cold-blooded animals, but it can infect humans. To
      define the phylogeny of this species, and compare it to S. enterica, we have
      sequenced 28 isolates representing most of the known diversity of S. bongori.
      This cross-species analysis allowed us to confidently differentiate ancestral
      functions from those acquired following speciation, which include both metabolic
      and virulence-associated capacities. We show that, although S. bongori inherited
      a basic set of Salmonella common virulence functions, it has subsequently
      elaborated on this in a different direction to S. enterica. It is an established
      feature of S. enterica evolution that the acquisition of the type III secretion
      systems (T3SS-1 and T3SS-2) has been followed by the sequential acquisition of
      genes encoding secreted targets, termed effectors proteins. We show that this is
      also true of S. bongori, which has acquired an array of novel effector proteins
      (sboA-L). All but two of these effectors have no significant S. enterica
      homologues and instead are highly similar to those found in enteropathogenic
      Escherichia coli (EPEC). Remarkably, SboH is found to be a chimeric effector
      protein, encoded by a fusion of the T3SS-1 effector gene sopA and a gene highly
      similar to the EPEC effector nleH from enteropathogenic E. coli. We demonstrate
      that representatives of these new effectors are translocated and that SboH,
      similarly to NleH, blocks intrinsic apoptotic pathways while being targeted to
      the mitochondria by the SopA part of the fusion. This work suggests that S.
      bongori has inherited the ancestral Salmonella virulence gene set, but has
      adapted by incorporating virulence determinants that resemble those employed by
      EPEC.

PMID- 21876674
TI  - Genetic architecture of a reinforced, postmating, reproductive isolation barrier
      between Neurospora species indicates evolution via natural selection.
AB  - A role for natural selection in reinforcing premating barriers is recognized, but
      selection for reinforcement of postmating barriers remains controversial.
      Organisms lacking evolvable premating barriers can theoretically reinforce
      postmating isolation, but only under restrictive conditions: parental investment
      in hybrid progeny must inhibit subsequent reproduction, and selected postmating
      barriers must restore parents' capacity to reproduce successfully. We show that
      reinforced postmating isolation markedly increases maternal fitness in the fungus
      Neurospora crassa, and we detect the evolutionary genetic signature of natural
      selection by quantitative trait locus (QTL) analysis of the reinforced barrier.
      Hybrid progeny of N. crassa and N. intermedia are highly inviable. Fertilization
      by local N. intermedia results in early abortion of hybrid fruitbodies, and we
      show that abortion is adaptive because only aborted maternal colonies remain
      fully receptive to future reproduction. In the first QTL analysis of postmating
      reinforcement in microbial eukaryotes, we identify 11 loci for abortive hybrid
      fruitbody development, including three major QTLs that together explain 30% of
      trait variance. One of the major QTLs and six QTLs of lesser effect are found on
      the mating-type determining chromosome of Neurospora. Several reinforcement QTLs
      are flanked by genetic markers showing either segregation distortion or non
      random associations with alleles at other loci in a cross between N. crassa of
      different clades, suggesting that the loci also are associated with local effects
      on same-species reproduction. Statistical analysis of the allelic effects
      distribution for abortive hybrid fruitbody development indicates its evolution
      occurred under positive selection. Our results strongly support a role for
      natural selection in the evolution of reinforced postmating isolation in N.
      crassa.

PMID- 21876675
TI  - An EMT-driven alternative splicing program occurs in human breast cancer and
      modulates cellular phenotype.
AB  - Epithelial-mesenchymal transition (EMT), a mechanism important for embryonic
      development, plays a critical role during malignant transformation. While much is
      known about transcriptional regulation of EMT, alternative splicing of several
      genes has also been correlated with EMT progression, but the extent of splicing
      changes and their contributions to the morphological conversion accompanying EMT
      have not been investigated comprehensively. Using an established cell culture
      model and RNA-Seq analyses, we determined an alternative splicing signature for
      EMT. Genes encoding key drivers of EMT-dependent changes in cell phenotype, such
      as actin cytoskeleton remodeling, regulation of cell-cell junction formation, and
      regulation of cell migration, were enriched among EMT-associated alternatively
      splicing events. Our analysis suggested that most EMT-associated alternative
      splicing events are regulated by one or more members of the RBFOX, MBNL, CELF,
      hnRNP, or ESRP classes of splicing factors. The EMT alternative splicing
      signature was confirmed in human breast cancer cell lines, which could be
      classified into basal and luminal subtypes based exclusively on their EMT
      associated splicing pattern. Expression of EMT-associated alternative mRNA
      transcripts was also observed in primary breast cancer samples, indicating that
      EMT-dependent splicing changes occur commonly in human tumors. The functional
      significance of EMT-associated alternative splicing was tested by expression of
      the epithelial-specific splicing factor ESRP1 or by depletion of RBFOX2 in
      mesenchymal cells, both of which elicited significant changes in cell morphology
      and motility towards an epithelial phenotype, suggesting that splicing regulation
      alone can drive critical aspects of EMT-associated phenotypic changes. The
      molecular description obtained here may aid in the development of new diagnostic
      and prognostic markers for analysis of breast cancer progression.

PMID- 21876676
TI  - The repertoire of ICE in prokaryotes underscores the unity, diversity, and
      ubiquity of conjugation.
AB  - Horizontal gene transfer shapes the genomes of prokaryotes by allowing rapid
      acquisition of novel adaptive functions. Conjugation allows the broadest range
      and the highest gene transfer input per transfer event. While conjugative
      plasmids have been studied for decades, the number and diversity of integrative
      conjugative elements (ICE) in prokaryotes remained unknown. We defined a large
      set of protein profiles of the conjugation machinery to scan over 1,000 genomes
      of prokaryotes. We found 682 putative conjugative systems among all major
      phylogenetic clades and showed that ICEs are the most abundant conjugative
      elements in prokaryotes. Nearly half of the genomes contain a type IV secretion
      system (T4SS), with larger genomes encoding more conjugative systems.
      Surprisingly, almost half of the chromosomal T4SS lack co-localized relaxases
      and, consequently, might be devoted to protein transport instead of conjugation.
      This class of elements is preponderant among small genomes, is less commonly
      associated with integrases, and is rarer in plasmids. ICEs and conjugative
      plasmids in proteobacteria have different preferences for each type of T4SS, but
      all types exist in both chromosomes and plasmids. Mobilizable elements outnumber
      self-conjugative elements in both ICEs and plasmids, which suggests an extensive
      use of T4SS in trans. Our evolutionary analysis indicates that switch of plasmids
      to and from ICEs were frequent and that extant elements began to differentiate
      only relatively recently. According to the present results, ICEs are the most
      abundant conjugative elements in practically all prokaryotic clades and might be
      far more frequently domesticated into non-conjugative protein transport systems
      than previously thought. While conjugative plasmids and ICEs have different means
      of genomic stabilization, their mechanisms of mobility by conjugation show
      strikingly conserved patterns, arguing for a unitary view of conjugation in
      shaping the genomes of prokaryotes by horizontal gene transfer.

PMID- 21876678
TI  - Chromosome painting reveals asynaptic full alignment of homologs and HIM-8
      dependent remodeling of X chromosome territories during Caenorhabditis elegans
      meiosis.
AB  - During early meiotic prophase, a nucleus-wide reorganization leads to sorting of
      chromosomes into homologous pairs and to establishing associations between
      homologous chromosomes along their entire lengths. Here, we investigate global
      features of chromosome organization during this process, using a chromosome
      painting method in whole-mount Caenorhabditis elegans gonads that enables
      visualization of whole chromosomes along their entire lengths in the context of
      preserved 3D nuclear architecture. First, we show that neither spatial proximity
      of premeiotic chromosome territories nor chromosome-specific timing is a major
      factor driving homolog pairing. Second, we show that synaptonemal complex
      independent associations can support full lengthwise juxtaposition of homologous
      chromosomes. Third, we reveal a prominent elongation of chromosome territories
      during meiotic prophase that initiates prior to homolog association and
      alignment. Mutant analysis indicates that chromosome movement mediated by
      association of chromosome pairing centers (PCs) with mobile patches of the
      nuclear envelope (NE)-spanning SUN-1/ZYG-12 protein complexes is not the primary
      driver of territory elongation. Moreover, we identify new roles for the X
      chromosome PC (X-PC) and X-PC binding protein HIM-8 in promoting elongation of X
      chromosome territories, separable from their role(s) in mediating local
      stabilization of pairing and association of X chromosomes with mobile SUN-1/ZYG
      12 patches. Further, we present evidence that HIM-8 functions both at and outside
      of PCs to mediate chromosome territory elongation. These and other data support a
      model in which synapsis-independent elongation of chromosome territories, driven
      by PC binding proteins, enables lengthwise juxtaposition of chromosomes, thereby
      facilitating assessment of their suitability as potential pairing partners.

PMID- 21876677
TI  - Genomic analysis of the necrotrophic fungal pathogens Sclerotinia sclerotiorum
      and Botrytis cinerea.
AB  - Sclerotinia sclerotiorum and Botrytis cinerea are closely related necrotrophic
      plant pathogenic fungi notable for their wide host ranges and environmental
      persistence. These attributes have made these species models for understanding
      the complexity of necrotrophic, broad host-range pathogenicity. Despite their
      similarities, the two species differ in mating behaviour and the ability to
      produce asexual spores. We have sequenced the genomes of one strain of S.
      sclerotiorum and two strains of B. cinerea. The comparative analysis of these
      genomes relative to one another and to other sequenced fungal genomes is provided
      here. Their 38-39 Mb genomes include 11,860-14,270 predicted genes, which share
      83% amino acid identity on average between the two species. We have mapped the S.
      sclerotiorum assembly to 16 chromosomes and found large-scale co-linearity with
      the B. cinerea genomes. Seven percent of the S. sclerotiorum genome comprises
      transposable elements compared to <1% of B. cinerea. The arsenal of genes
      associated with necrotrophic processes is similar between the species, including
      genes involved in plant cell wall degradation and oxalic acid production.
      Analysis of secondary metabolism gene clusters revealed an expansion in number
      and diversity of B. cinerea-specific secondary metabolites relative to S.
      sclerotiorum. The potential diversity in secondary metabolism might be involved
      in adaptation to specific ecological niches. Comparative genome analysis revealed
      the basis of differing sexual mating compatibility systems between S.
      sclerotiorum and B. cinerea. The organization of the mating-type loci differs,
      and their structures provide evidence for the evolution of heterothallism from
      homothallism. These data shed light on the evolutionary and mechanistic bases of
      the genetically complex traits of necrotrophic pathogenicity and sexual mating.
      This resource should facilitate the functional studies designed to better
      understand what makes these fungi such successful and persistent pathogens of
      agronomic crops.

PMID- 21876679
TI  - Frequent beneficial mutations during single-colony serial transfer of
      Streptococcus pneumoniae.
AB  - The appearance of new mutations within a population provides the raw material for
      evolution. The consistent decline in fitness observed in classical mutation
      accumulation studies has provided support for the long-held view that deleterious
      mutations are more common than beneficial mutations. Here we present results of a
      study using a mutation accumulation design with the bacterium Streptococcus
      pneumoniae in which the fitness of the derived populations increased. This rise
      in fitness was associated specifically with adaptation to survival during brief
      stationary phase periods between single-colony population bottlenecks. To
      understand better the population dynamics behind this unanticipated adaptation,
      we developed a maximum likelihood model describing the processes of mutation and
      stationary-phase selection in the context of frequent population bottlenecks.
      Using this model, we estimate that the rate of beneficial mutations may be as
      high as 4.8*10(-4) events per genome for each time interval corresponding to the
      pneumococcal generation time. This rate is several orders of magnitude higher
      than earlier estimates of beneficial mutation rates in bacteria but supports
      recent results obtained through the propagation of small populations of
      Escherichia coli. Our findings indicate that beneficial mutations may be
      relatively frequent in bacteria and suggest that in S. pneumoniae, which develops
      natural competence for transformation, a steady supply of such mutations may be
      available for sampling by recombination.

PMID- 21876680
TI  - A comprehensive map of mobile element insertion polymorphisms in humans.
AB  - As a consequence of the accumulation of insertion events over evolutionary time,
      mobile elements now comprise nearly half of the human genome. The Alu, L1, and
      SVA mobile element families are still duplicating, generating variation between
      individual genomes. Mobile element insertions (MEI) have been identified as
      causes for genetic diseases, including hemophilia, neurofibromatosis, and various
      cancers. Here we present a comprehensive map of 7,380 MEI polymorphisms from the
      1000 Genomes Project whole-genome sequencing data of 185 samples in three major
      populations detected with two detection methods. This catalog enables us to
      systematically study mutation rates, population segregation, genomic
      distribution, and functional properties of MEI polymorphisms and to compare MEI
      to SNP variation from the same individuals. Population allele frequencies of MEI
      and SNPs are described, broadly, by the same neutral ancestral processes despite
      vastly different mutation mechanisms and rates, except in coding regions where
      MEI are virtually absent, presumably due to strong negative selection. A direct
      comparison of MEI and SNP diversity levels suggests a differential mobile element
      insertion rate among populations.

PMID- 21876682
TI  - DNA methylation and histone modifications regulate de novo shoot regeneration in
      Arabidopsis by modulating WUSCHEL expression and auxin signaling.
AB  - Plants have a profound capacity to regenerate organs from differentiated somatic
      tissues, based on which propagating plants in vitro was made possible. Beside its
      use in biotechnology, in vitro shoot regeneration is also an important system to
      study de novo organogenesis. Phytohormones and transcription factor WUSCHEL (WUS)
      play critical roles in this process but whether and how epigenetic modifications
      are involved is unknown. Here, we report that epigenetic marks of DNA methylation
      and histone modifications regulate de novo shoot regeneration of Arabidopsis
      through modulating WUS expression and auxin signaling. First, functional loss of
      key epigenetic genes-including METHYLTRANSFERASE1 (MET1) encoding for DNA
      methyltransferase, KRYPTONITE (KYP) for the histone 3 lysine 9 (H3K9)
      methyltransferase, JMJ14 for the histone 3 lysine 4 (H3K4) demethylase, and HAC1
      for the histone acetyltransferase-resulted in altered WUS expression and
      developmental rates of regenerated shoots in vitro. Second, we showed that
      regulatory regions of WUS were developmentally regulated by both DNA methylation
      and histone modifications through bisulfite sequencing and chromatin
      immunoprecipitation. Third, DNA methylation in the regulatory regions of WUS was
      lost in the met1 mutant, thus leading to increased WUS expression and its
      localization. Fourth, we did a genome-wide transcriptional analysis and found out
      that some of differentially expressed genes between wild type and met1 were
      involved in signal transduction of the phytohormone auxin. We verified that the
      increased expression of AUXIN RESPONSE FACTOR3 (ARF3) in met1 indeed was due to
      DNA demethylation, suggesting DNA methylation regulates de novo shoot
      regeneration by modulating auxin signaling. We propose that DNA methylation and
      histone modifications regulate de novo shoot regeneration by modulating WUS
      expression and auxin signaling. The study demonstrates that, although molecular
      components involved in organogenesis are divergently evolved in plants and
      animals, epigenetic modifications play an evolutionarily convergent role in this
      process.

PMID- 21876683
TI  - A broad brush, global overview of bacterial sexuality.

PMID- 21876681
TI  - Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a
      Parkinson's disease modifier gene via interaction with coffee.
AB  - Our aim was to identify genes that influence the inverse association of coffee
      with the risk of developing Parkinson's disease (PD). We used genome-wide
      genotype data and lifetime caffeinated-coffee-consumption data on 1,458 persons
      with PD and 931 without PD from the NeuroGenetics Research Consortium (NGRC), and
      we performed a genome-wide association and interaction study (GWAIS), testing
      each SNP's main-effect plus its interaction with coffee, adjusting for sex, age,
      and two principal components. We then stratified subjects as heavy or light
      coffee-drinkers and performed genome-wide association study (GWAS) in each group.
      We replicated the most significant SNP. Finally, we imputed the NGRC dataset,
      increasing genomic coverage to examine the region of interest in detail. The
      primary analyses (GWAIS, GWAS, Replication) were performed using genotyped data.
      In GWAIS, the most significant signal came from rs4998386 and the neighboring
      SNPs in GRIN2A. GRIN2A encodes an NMDA-glutamate-receptor subunit and regulates
      excitatory neurotransmission in the brain. Achieving P(2df) = 10(-6), GRIN2A
      surpassed all known PD susceptibility genes in significance in the GWAIS. In
      stratified GWAS, the GRIN2A signal was present in heavy coffee-drinkers (OR =
      0.43; P = 6*10(-7)) but not in light coffee-drinkers. The a priori Replication
      hypothesis that "Among heavy coffee-drinkers, rs4998386_T carriers have lower PD
      risk than rs4998386_CC carriers" was confirmed: OR(Replication) = 0.59,
      P(Replication) = 10(-3); OR(Pooled) = 0.51, P(Pooled) = 7*10(-8). Compared to
      light coffee-drinkers with rs4998386_CC genotype, heavy coffee-drinkers with
      rs4998386_CC genotype had 18% lower risk (P = 3*10(-3)), whereas heavy coffee
      drinkers with rs4998386_TC genotype had 59% lower risk (P = 6*10(-13)).
      Imputation revealed a block of SNPs that achieved P(2df)<5*10(-8) in GWAIS, and
      OR = 0.41, P = 3*10(-8) in heavy coffee-drinkers. This study is proof of concept
      that inclusion of environmental factors can help identify genes that are missed
      in GWAS. Both adenosine antagonists (caffeine-like) and glutamate antagonists
      (GRIN2A-related) are being tested in clinical trials for treatment of PD. GRIN2A
      may be a useful pharmacogenetic marker for subdividing individuals in clinical
      trials to determine which medications might work best for which patients.

PMID- 21876684
TI  - Synthesis, Crystal Structure, and DNA-Binding Studies of a Nickel(II) Complex
      with the Bis(2-benzimidazolymethyl)amine Ligand.
AB  - A V-shaped ligand Bis(2-benzimidazolymethyl)amine (bba) and its nickel(II)
      picrate (pic) complex, with composition [Ni(bba)(2)](pic)(2).3MeOH, have been
      synthesized and characterized on the basis of elemental analyses, molar
      conductivities, IR spectra, and UV/vis measurements. In the complex, the Ni(II)
      ion is six-coordinated with a N(2)O(4) ligand set, resulting in a distorted
      octahedron coordination geometry. In addition, the DNA-binding properties of the
      Ni(II) complex have been investigated by electronic absorption, fluorescence, and
      viscosity measurements. The experimental results suggest that the nickel(II)
      complex binds to DNA by partial intercalation binding mode.

PMID- 21876685
TI  - A novel wheat variety with elevated content of amylose increases resistant starch
      formation and may beneficially influence glycaemia in healthy subjects.
AB  - BACKGROUND: Previous studies indicate that elevated amylose content in products
      from rice, corn, and barley induce lower postprandial glycaemic responses and
      higher levels of resistant starch (RS). Consumption of slowly digestible
      carbohydrates and RS has been associated with health benefits such as decreased
      risk of diabetes and cardiovascular disease. OBJECTIVE: To evaluate the
      postprandial glucose and insulin responses in vivo to bread products based on a
      novel wheat genotype with elevated amylose content (38%). DESIGN: Bread was baked
      from a unique wheat genotype with elevated amylose content, using baking
      conditions known to promote amylose retrogradation. Included test products were
      bread based on whole grain wheat with elevated amylose content (EAW), EAW with
      added lactic acid (EAW-la), and ordinary whole grain wheat bread (WGW). All test
      breads were baked at pumpernickel conditions (20 hours, 120 degrees C). A
      conventionally baked white wheat bread (REF) was used as reference. Resistant
      starch (RS) content was measured in vitro and postprandial glucose and insulin
      responses were tested in 14 healthy subjects. RESULTS: The results showed a
      significantly higher RS content (on total starch basis) in breads based on EAW
      than in WGW (p<0.001). Lactic acid further increased RS (p<0.001) compared with
      both WGW and EAW. Breads baked with EAW induced lower postprandial glucose
      response than REF during the first 120 min (p<0.05), but there were no
      significant differences in insulin responses. Increased RS content per test
      portion was correlated to a reduced glycaemic index (GI) (r=-0.571, p<0.001).
      CONCLUSIONS: This study indicates that wheat with elevated amylose content may be
      preferable to other wheat genotypes considering RS formation. Further research is
      needed to test the hypothesis that bread with elevated amylose content can
      improve postprandial glycaemic response.

PMID- 21876686
TI  - Multistrategy self-organizing map learning for classification problems.
AB  - Multistrategy Learning of Self-Organizing Map (SOM) and Particle Swarm
      Optimization (PSO) is commonly implemented in clustering domain due to its
      capabilities in handling complex data characteristics. However, some of these
      multistrategy learning architectures have weaknesses such as slow convergence
      time always being trapped in the local minima. This paper proposes multistrategy
      learning of SOM lattice structure with Particle Swarm Optimisation which is
      called ESOMPSO for solving various classification problems. The enhancement of
      SOM lattice structure is implemented by introducing a new hexagon formulation for
      better mapping quality in data classification and labeling. The weights of the
      enhanced SOM are optimised using PSO to obtain better output quality. The
      proposed method has been tested on various standard datasets with substantial
      comparisons with existing SOM network and various distance measurement. The
      results show that our proposed method yields a promising result with better
      average accuracy and quantisation errors compared to the other methods as well as
      convincing significant test.

PMID- 21876687
TI  - Language and cognition interaction neural mechanisms.
AB  - How language and cognition interact in thinking? Is language just used for
      communication of completed thoughts, or is it fundamental for thinking? Existing
      approaches have not led to a computational theory. We develop a hypothesis that
      language and cognition are two separate but closely interacting mechanisms.
      Language accumulates cultural wisdom; cognition develops mental representations
      modeling surrounding world and adapts cultural knowledge to concrete
      circumstances of life. Language is acquired from surrounding language "ready
      made" and therefore can be acquired early in life. This early acquisition of
      language in childhood encompasses the entire hierarchy from sounds to words, to
      phrases, and to highest concepts existing in culture. Cognition is developed from
      experience. Yet cognition cannot be acquired from experience alone; language is a
      necessary intermediary, a "teacher." A mathematical model is developed; it
      overcomes previous difficulties and leads to a computational theory. This model
      is consistent with Arbib's "language prewired brain" built on top of mirror
      neuron system. It models recent neuroimaging data about cognition, remaining
      unnoticed by other theories. A number of properties of language and cognition are
      explained, which previously seemed mysterious, including influence of language
      grammar on cultural evolution, which may explain specifics of English and Arabic
      cultures.

PMID- 21876688
TI  - Review of diagnostic imaging modalities for the surveillance of melanoma
      patients.
AB  - As melanoma survival rates continue to increase, optimal surveillance strategies
      for recurrences are needed, as are effective imaging modalities. Therefore, we
      performed a meta-analysis to evaluate the current state of imaging modalities for
      surveillance of melanoma in the published medical literature to determine the
      sensitivity, specificity, and positive predictive values of ultrasonography,
      computed tomography (CT), positron emission tomography (PET), and CT-PET
      combined. Ultrasonography was found to be the most sensitive and specific for
      detecting lymph node metastases, and PET-CT was the most sensitive and specific
      for detecting distant metastases. In addition to identifying appropriate
      surveillance methods, future studies should focus on the most effective and cost
      effective intervals for performing these tests. In addition, the results from the
      meta-analysis related to sensitivity and specificity of the tests should be made
      available to doctors in community practice.

PMID- 21876689
TI  - Comparative Effects of alpha-, beta-, and gamma-Carbolines on Platelet
      Aggregation and Lipid Membranes.
AB  - Cigarette smoking and alcohol consumption possibly affect platelet functions. To
      verify the hypothesis that some alpha-, beta-, and gamma-carboline components in
      cigarette smoke and alcoholic beverages may change platelet aggregability, their
      effects on human platelets were determined by aggregometry together with
      investigating their membrane effects by turbidimetry. Carbolines inhibited
      platelet aggregation induced by five agents with the potency being 3-amino-1,4
      dimethyl-5H-pyrido[4,3-b]indole > 3-amino-1-methyl-5H-pyrido[4,3-b]indole > 1
      methyl-9H-pyrido[3,4-b]indole. The most potent 3-amino-1,4-dimethyl-5H-pyrido[4,3
      b]indole showed 50% aggregation-inhibitory concentrations of 6-172 MUM. Both
      gamma-carbolines interacted with phosphatidylcholine membranes to lower the lipid
      phase transition temperature with the potency correlating to the antiplatelet
      activity, suggesting that the interaction with platelet membranes to increase
      their fluidity underlies antiplatelet effects. Given their possible concentration
      and accumulation in platelets, gamma- and beta-carbolines would provide cigarette
      smokers and alcohol drinkers with reduced platelet aggregability, and they may be
      responsible for the occurrence of hemorrhagic diseases associated with heavy
      smoking and alcoholics.

PMID- 21876691
TI  - Shortening and Improving the Embryonic Stem Cell Test through the Use of Gene
      Biomarkers of Differentiation.
AB  - The embryonic Stem cell Test (EST) is a validated assay for testing
      embryotoxicity in vitro. The total duration of this protocol is 10 days, and its
      main end-point is based on histological determinations. It is suggested that
      improvements on EST must be focused toward molecular end-points and, if possible,
      to reduce the total assay duration. Five days of exposure of D3 cells in
      monolayers under spontaneous differentiation to 50 ng/mL of the strong
      embryotoxic 5-fluorouracil or to 75 MUg/mL of the weak embryotoxic 5,5
      diphenylhydeantoin caused between 20 and 74% of reductions in the expression of
      the following genes: Pnpla6, Afp, Hdac7, Vegfa, and Nes. The exposure to 1 mg/mL
      of nonembryotoxic saccharin only caused statistically significant reductions in
      the expression of Nes. These exposures reduced cell viability of D3 cells by 15,
      28, and 34%. We applied these records to the mathematical discriminating function
      of the EST method to find that this approach is able to correctly predict the
      embryotoxicity of all three above-mentioned chemicals. Therefore, this work
      proposes the possibility of improve EST by reducing its total duration and by
      introducing gene expression as biomarker of differentiation, which might be very
      interesting for in vitro risk assessment embryotoxicity.

PMID- 21876690
TI  - Liposomal Antioxidants for Protection against Oxidant-Induced Damage.
AB  - Reactive oxygen species (ROS), including superoxide anion, hydrogen peroxide, and
      hydroxyl radical, can be formed as normal products of aerobic metabolism and can
      be produced at elevated rates under pathophysiological conditions. Overproduction
      and/or insufficient removal of ROS result in significant damage to cell structure
      and functions. In vitro studies showed that antioxidants, when applied directly
      and at relatively high concentrations to cellular systems, are effective in
      conferring protection against the damaging actions of ROS, but results from
      animal and human studies showed that several antioxidants provide only modest
      benefit and even possible harm. Antioxidants have yet to be rendered into
      reliable and safe therapies because of their poor solubility, inability to cross
      membrane barriers, extensive first-pass metabolism, and rapid clearance from
      cells. There is considerable interest towards the development of drug-delivery
      systems that would result in the selective delivery of antioxidants to tissues in
      sufficient concentrations to ameliorate oxidant-induced tissue injuries.
      Liposomes are biocompatible, biodegradable, and nontoxic artificial phospholipid
      vesicles that offer the possibility of carrying hydrophilic, hydrophobic, and
      amphiphilic molecules. This paper focus on the use of liposomes for the delivery
      of antioxidants in the prevention or treatment of pathological conditions related
      to oxidative stress.

PMID- 21876692
TI  - Revelations from the Nematode Caenorhabditis elegans on the Complex Interplay of
      Metal Toxicological Mechanisms.
AB  - Metals have been definitively linked to a number of disease states. Due to the
      widespread existence of metals in our environment from both natural and
      anthropogenic sources, understanding the mechanisms of their cellular
      detoxification is of upmost importance. Organisms have evolved cellular
      detoxification systems including glutathione, metallothioneins, pumps and
      transporters, and heat shock proteins to regulate intracellular metal levels. The
      model organism, Caenorhabditis elegans (C. elegans), contains these systems and
      provides several advantages for deciphering the mechanisms of metal
      detoxification. This review provides a brief summary of contemporary literature
      on the various mechanisms involved in the cellular detoxification of metals,
      specifically, antimony, arsenic, cadmium, copper, manganese, mercury, and
      depleted uranium using the C. elegans model system for investigation and
      analysis.

PMID- 21876694
TI  - Targeting angiogenesis for controlling neuroblastoma.
AB  - Neuroblastoma, a progressive solid tumor in childhood, continues to be a clinical
      challenge. It is highly vascular, heterogeneous, and extracranial tumor that
      originates from neural crest. Angiogenesis, genetic abnormalities, and oncogene
      amplification are mainly responsible for malignant phenotype of this tumor.
      Survivability of malignant neuroblastoma patients remains poor despite the use of
      traditional therapeutic strategies. Angiogenesis is a very common and necessary
      pre-requisite for tumor progression and metastasis. Angiogenesis is also a major
      factor in making malignant neuroblastoma. Thus, prevention of angiogenesis can be
      a highly significant strategy in the treatment of malignant neuroblastoma. Here,
      we summarize our current understanding of angiogenesis in malignant neuroblstoma
      and describe the use of experimental anti-angiogenic agents either alone or in
      combination therapy. This review will clearly indicate the importance of
      angiogenesis in the pathogenesis of malignant neuroblastoma, its prevention as a
      promising therapy in preclinical models of malignant neuroblastoma, and
      prospective clinical trials.

PMID- 21876695
TI  - Experimental and modeling study of collagen scaffolds with the effects of
      crosslinking and fiber alignment.
AB  - Collagen type I scaffolds are commonly used due to its abundance,
      biocompatibility, and ubiquity. Most applications require the scaffolds to
      operate under mechanical stresses. Therefore understanding and being able to
      control the structural-functional integrity of collagen scaffolds becomes
      crucial. Using a combined experimental and modeling approach, we studied the
      structure and function of Type I collagen gel with the effects of spatial fiber
      alignment and crosslinking. Aligned collagen scaffolds were created through the
      flow of magnetic particles enmeshed in collagen fibrils to mimic the anisotropy
      seen in native tissue. Inter- and intra- molecular crosslinking was modified
      chemically with Genipin to further improve the stiffness of collagen scaffolds.
      The anisotropic mechanical properties of collagen scaffolds were characterized
      using a planar biaxial tensile tester and parallel plate rheometer. The tangent
      stiffness from biaxial tensile test is two to three orders of magnitude higher
      than the storage moduli from rheological measurements. The biphasic nature of
      collagen gel was discussed and used to explain the mechanical behavior of
      collagen scaffolds under different types of mechanical tests. An anisotropic
      hyperelastic constitutive model was used to capture the characteristics of the
      stress-strain behavior exhibited by collagen scaffolds.

PMID- 21876696
TI  - Band 3 missense mutations and stomatocytosis: insight into the molecular
      mechanism responsible for monovalent cation leak.
AB  - Missense mutations in the erythroid band 3 protein (Anion Exchanger 1) have been
      associated with hereditary stomatocytosis. Features of cation leaky red cells
      combined with functional expression of the mutated protein led to the conclusion
      that the AE1 point mutations were responsible for Na(+) and K(+) leak through a
      conductive mechanism. A molecular mechanism explaining mutated AE1-linked
      stomatocytosis involves changes in AE1 transport properties that become leaky to
      Na(+) and K(+). However, another explanation suggests that point-mutated AE1
      could regulate a cation leak through other transporters. This short paper intends
      to discuss these two alternatives.

PMID- 21876693
TI  - Targeting the tumor microenvironment: focus on angiogenesis.
AB  - Tumorigenesis is a complex multistep process involving not only genetic and
      epigenetic changes in the tumor cell but also selective supportive conditions of
      the deregulated tumor microenvironment. One key compartment of the
      microenvironment is the vascular niche. The role of angiogenesis in solid tumors
      but also in hematologic malignancies is now well established. Research on
      angiogenesis in general, and vascular endothelial growth factor in particular, is
      a major focus in biomedicine and has led to the clinical approval of several
      antiangiogenic agents including thalidomide, bevacizumab, sorafenib, sunitinib,
      pazopanib, temesirolimus, and everolimus. Indeed, antiangiogenic agents have
      significantly changed treatment strategies in solid tumors (colorectal cancer,
      renal cell carcinoma, and breast cancer) and multiple myeloma. Here we illustrate
      important aspects in the interrelationship between tumor cells and the
      microenvironment leading to tumor progression, with focus on angiogenesis, and
      summarize derived targeted therapies.

PMID- 21876697
TI  - erbB2 Overexpression in Uterine Serous Cancer: A Molecular Target for Trastuzumab
      Therapy.
AB  - Endometrial cancer is the most common female genital tract malignancy in the
      United States. Type I endometrial cancer is usually diagnosed at an early stage,
      and has a good prognosis. Type II is very aggressive, and is responsible for most
      uterine cancer relapses and deaths. Uterine serous adenocarcinomas (USC)
      constitute the majority of Type II variants. They have a higher propensity for
      lymph node and distant metastases. They are frequently aneuploid and associated
      with p53 mutations. erbB2 overexpression in USC has been described. The
      incidence, which is higher in African Americans, ranges from 18-80%. erbB2
      overexpression was found to be associated with higher stage, chemoresistance, and
      worse survival. Trastuzumab a humanized mAb was approved by the FDA for treatment
      of breast cancers that overexpress erbB2 in combination with standard
      chemotherapy. Evidence of trastuzumab activity in USC has been reported in vitro,
      as well as in case reports of advanced and recurrent cases. Promising results
      were obtained in these heavily pretreated patients either with trastuzumab alone
      or in combination with chemotherapy. This supports the hypothesis that
      trastuzumab may very well be an attractive and viable treatment option for
      advanced stage USC tumors that overexpress the erbB2, and is worthy of further
      study.

PMID- 21876698
TI  - Blocking Epidermal Growth Factor Receptor Signaling in HTR-8/SVneo First
      Trimester Trophoblast Cells Results in Dephosphorylation of PKBalpha/AKT and
      Induces Apoptosis.
AB  - We identified a major peptide signaling target of EGF/EGFR pathway and explored
      the consequences of blocking or activating this pathway in the first trimester
      extravillous trophoblast cells, HTR-8/SVneo. A global analysis of protein
      phosphorylation was undertaken using novel technology (Kinexus Kinetworks) that
      utilizes SDS-polyacrylamide minigel electrophoresis and multi-lane immunoblotting
      to permit specific and semiquantitative detection of multiple phosphoproteins.
      Forty-seven protein phosphorylation sites were queried, and the results reported
      based on relative phosphorylation at each site. EGF- and Iressa-(gefitinib,
      ZD1839, an inhibitor of EGFR) treated HTR-8/SVneo cells were subjected to
      immunoblotting and flow cytometry to confirm the phosphoprotein screen and to
      assess the effects of EGF versus Iressa on cell cycle and apoptosis. EGFR
      mediates the phosphorylation of important signaling proteins, including
      PKBalpha/AKT. This pathway is likely to be central to EGFR-mediated trophoblast
      survival. Furthermore, EGF treatment induces proliferation and inhibits
      apoptosis, while Iressa induces apoptosis.

PMID- 21876699
TI  - Severe hemoperitoneum after patient self-induced fecal evacuation.
AB  - An increasing incidence of rectal injuries following patient self-induced harmful
      acts, aimed to sexual or laxatives porpouses, is a fact reported in literature
      (El-Ashaal et al., 2008). We herein report a case of severe hemoperitoneum
      related to a middle and upper rectal third seromuscolar tear caused by a self
      induced fecal evacuation by means of an arrow with a covered cork tip. An urgent
      intestinal diversion by means of a Hartmann's operation was performed. The
      clinical case is presented in relation to the literature debate, regarding the
      issue of primary repair or resection and anastomosis versus fecal diversion for
      penetrating rectal injuries (Fabian, 2002; Cleary et al., 2006; Office of the
      Surgeon General, 1943; Busic et al., 2002). In conclusion, the importance of
      avoiding an anastomotic breakdown in a patient undergoing a hemorrhagic shock is
      highlighted.

PMID- 21876700
TI  - Posttraumatic cranial cystic fibrous dysplasia.
AB  - A 14-year-old was girl admitted to our hospital with a subcutaneous mass of the
      occipital head. The mass had grown for 6 years, after she had sustained a head
      injury at the age of 6, and was located directly under a previous wound. Skull X
      ray Photograph (xp), computed tomography (CT), and magnetic resonance imaging
      (MRI) showed a bony defect and cystic changes in the skull corresponding to a
      subcutaneous mass. Bone scintigraphy revealed partial accumulation. The patient
      underwent total removal of the skull mass, and the diagnosis from the
      pathological findings of the cyst wall was fibrous dysplasia (FD). The
      radiographic findings for cystic cranial FD can be various. Progressive skull
      disease has been reported to be associated with head trauma, but the relationship
      between cranial FD and head trauma has not been previously reported. Previous
      studies have suggested that c-fos gene expression is a key mechanism in injury
      induced FD.

PMID- 21876701
TI  - Operative Management of Sciatic Nerve Palsy due to Impingement on the Metal Cage
      after Total Hip Revision: Case Report.
AB  - This paper discusses a sciatic nerve palsy developed after a right total hip
      revision with a Burch-Schneider metal cage. A sciatalgic nerve pain appeared
      after surgery, while the palsy developed in about fifteen days. An
      electromyography showed the delay of the nerve impulse gluteal level. During the
      surgical exploration of the hip, a compression of the nerve on the metal cage was
      observed. The nerve was isolated, released from the fibrotic tissue and from the
      impingement, and was protected with a muscular flap. The recover from the pain
      was immediate, while the palsy recovered one month later.

PMID- 21876702
TI  - The role of 3-dimensional power Doppler imaging in the assessment of ovarian
      teratoma in pregnancy: a case report.
AB  - Background. Conventional sonography is the primary imaging tool for these
      pregnant women who present with an ovarian teratoma. In some cases, however,
      sonography diagnosis is difficult. We report a case of ovarian teratoma during
      pregnancy diagnosed by three-dimensional Power Doppler. The cyst was removed via
      laparotomy without fetal or maternal complications. Three-dimensional ultrasound
      with multiplanar view can better discriminate a benign ovarian teratoma from
      complex ovarian lesions or malignant tumors. Its role is significant especially
      during pregnancy as it may assist in determining which patients are requiring
      surgery and which are not. The results of three-dimensional sonography and
      magnetic resonance (MR) were equal but the role of MR imaging is limited in early
      pregnancy. Conclusions. Three-dimensional technique is a reliable diagnostic
      modality for preoperative assessment of an ovarian teratoma as it can be
      performed during the first trimester of pregnancy.

PMID- 21876703
TI  - Staged concept for treatment of severe postsaphenectomy wound infection.
AB  - The saphenous vein remains the most commonly used conduit in coronary artery
      bypass surgery. Vein harvest is a critical component with significant morbidity
      associated with leg wounds from open technique. Occurring complications are
      hematoma, postoperative pain, skin changes, neuropathy, and septic or nonseptic
      wound complications. Within the context of a recent case, we present our approach
      to postsaphenectomy wound management.

PMID- 21876704
TI  - The impact of bioactive lipids on cardiovascular development.
AB  - Lysophospholipids comprise a group of bioactive molecules with multiple
      biological functions. The cardinal members of this signalling molecule group are
      sphingosylphosphorylcholine (SPC), lysophosphatidic acid (LPA), and sphingosine 1
      phosphate (S1P) which are, at least in part, homologous to each other. Bioactive
      lipids usually act via G-protein coupled receptors (GPCRs), but can also function
      as direct intracellular messengers. Recently, it became evident that bioactive
      lipids play a role during cellular differentiation development. SPC induces
      mesodermal differentiation of mouse ES cells and differentiation of promyelocytic
      leukemia cells, by a mechanism being critically dependent on MEK-ERK signalling.
      LPA stimulates the clonal expansion of neurospheres from neural stem/progenitor
      cells and induces c-fos via activation of mitogen- and stress-activated protein
      kinase 1 (MSK1) in ES cells. S1P acts on hematopoietic progenitor cells as a
      chemotactic factor and has also been found to be critical for cardiac and
      skeletal muscle regeneration. Furthermore, S1P promotes cardiogenesis and
      similarly activates Erk signalling in mouse ES cells. Interestingly, S1P may also
      act to maintain human stem cell pluripotency. Both LPA and S1P positively
      regulate the proliferative capacity of murine ES cells. In this paper we will
      focus on the differential and developmental impact of lysophospholipids on
      cardiovascular development.

PMID- 21876706
TI  - Prevalence of congenital malaria in minna, north central Nigeria.
AB  - The study was designed to determine the true prevalence of congenital, cord, and
      placental malaria in General Hospital Minna, North Central Nigeria. Peripheral
      blood smears of near-term pregnant women, as well as the placental, cord, and
      peripheral blood smears of their newborn babies, were examined for malaria
      parasites, using the Giemsa staining technique. Out of 152 pregnant women
      screened, 21 (13.82%) of them were infected with malaria parasites. Of the 152
      new born babies, 4 (2.63%) showed positive peripheral parasitaemia. Placental
      parasitaemia was 7/152 (4.61%), while cord blood parasitaemia was 9/152 (5.92%).
      There were strong associations between peripheral and cord malaria parasitaemia
      and congenital malaria (P < 0.05). Plasmodium falciparum occurred in all, and
      none had mixed infection. The average birth weights of the babies delivered of
      nonmalarious pregnant women were higher than those delivered by malarious
      pregnant women, though not significant (P > 0.05). Malaria parasitaemia occurred
      more frequently in primigravidae than multigravidae.

PMID- 21876705
TI  - Low- and high-tech approaches to control Plasmodium parasite transmission by
      anopheles mosquitoes.
AB  - Current efforts have proven inadequate to stop the transmission of Plasmodium
      parasites, and hence the spread of malaria, by Anopheles mosquitoes. Therefore, a
      novel arsenal of strategies for inhibiting Plasmodium infection of mosquitoes is
      urgently needed. In this paper, we summarize research on two approaches to
      malaria control, a low-tech strategy based on parasite inhibition by the
      mosquito's natural microflora, and a high-tech strategy using genetic
      modification of mosquitoes that renders them resistant to infection and discuss
      advantages and disadvantages for both approaches.

PMID- 21876707
TI  - Management and outcome in 32 neonates with thrombotic events.
AB  - Objective. To determine the incidence, management, complications, and outcome in
      neonates with thrombotic events. Study Design. We performed a retrospective study
      of all neonates with thrombotic events admitted to our neonatal intensive care
      unit from January 2004 to July 2010. Results. Thrombotic events were identified
      in 32 of 4734 neonates (0.7%). Seven neonates were managed expectantly and 25
      neonates received anticoagulant treatment. Complete resolution of the clot within
      3 months of age was found in 68% (17/25) of the treated and in 86% (6/7) of the
      nontreated neonates. Major complications due to anticoagulant therapy occurred in
      3/25 cases (12%) and included severe hemorrhage (n = 2) and abscess at the
      injection site (n = 1). Conclusion. Complete or partial clot resolution in
      neonatal thrombosis occurred in both the treated group and nontreated group.
      Randomized controlled trials are warranted to determine the optimal management in
      neonatal thrombosis.

PMID- 21876708
TI  - HLA-B57 and gender influence the occurrence of tuberculosis in HIV infected
      people of south India.
AB  - BACKGROUND: Substantial evidence exists for HLA and other host genetic factors
      being determinants of susceptibility or resistance to infectious diseases.
      However, very little information is available on the role of host genetic factors
      in HIV-TB coinfection. Hence, a longitudinal study was undertaken to investigate
      HLA associations in a cohort of HIV seropositive individuals with and without TB
      in Bangalore, South India. METHODS: A cohort of 238 HIV seropositive subjects
      were typed for HLA-A, B, and DR by PCR-SSP and followed up for 5 years or till
      manifestation of Tuberculosis. HLA data of 682 HIV Negative healthy renal donors
      was used as control. RESULTS: The ratio of males and females in HIV cohort was
      comparable (50.4% and 49.6%). But the incidence of TB was markedly lower in
      females (12.6%,) than males (25.6%). Further, HLA-B*57 frequency in HIV cohort
      was significantly higher among females without TB (21.6%, 19/88) than males
      (1.7%, 1/59); P = 0.0046; OR = 38. CD4 counts also were higher among females in
      this cohort. CONCLUSION: This study suggests that HIV positive women with HLA
      B*57 have less occurrence of TB as compared to males.

PMID- 21876709
TI  - Association between functional polymorphisms of Foxp3 gene and the occurrence of
      unexplained recurrent spontaneous abortion in a Chinese Han population.
AB  - Unexplained recurrent spontaneous abortion (URSA) is an alloimmune disease
      associated with the failure of fetal-maternal immunologic tolerance in which the
      regulatory T lymphocytes (Treg) play a pivotal role. It is well known that
      Forkhead box P3 (Foxp3) is a crucial regulatory factor for the development and
      function of Treg cells. It has also been established that deficiency of the Foxp3
      gene suppresses the regulatory function of Treg cells. To determine if functional
      polymorphisms at the Foxp3 loci are associated with URSA in humans, we genotyped
      four common polymorphisms of Foxp3 gene in 146 unrelated URSA patients and 112
      healthy women. The results showed that rs3761548A/C and rs2232365A/G
      polymorphisms were significantly associated with URSA. Additionally, we found
      that the allelic distribution of rs5902434 del/ATT in URSA group was slightly
      different from that in the control group. We conclude that functional
      polymorphisms of the Foxp3 gene may confer an important susceptibility to URSA in
      the Chinese Han population, probably by altering Foxp3 function and/or its
      expression.

PMID- 21876710
TI  - Discovery of diagnosis pattern of coronary heart disease with qi deficiency
      syndrome by the T-test-based adaboost algorithm.
AB  - Coronary heart disease (CHD) is still the leading cause of death for adults
      worldwide. Traditional Chinese medicine (TCM) has a history of 1000 years
      fighting against the disease and provides a complementary and alternative
      treatment to it. Syndrome is the core of TCM diagnosis and it is traditionally
      diagnosed based on macroscopic symptoms as well as tongue and pulse recognitions
      of patients. Establishment of the diagnosis method in the microcosmic level is an
      urgent and major problem in TCM. The aim of this study was to establish
      characteristic diagnosis pattern for CHD with Qi deficiency syndrome (QDS).
      Thirty-four biological parameters were detected in 52 patients having unstable
      angina (UA) with or without QDS. Then, we presented a novel data mining method, t
      test-based Adaboost algorithm, to establish highest prediction accuracy with the
      least number of biological parameters for UA with QDS. We gained a pattern
      composed of five biological parameters that distinguishes UA with QDS patients
      from non-QDS patients. The diagnosis accuracy of the patterns could reach 84.5%
      based on a 3-fold cross validation technique. Moreover, we included 85 UA cases
      collected from hospitals located in the north and south of China to further
      verify the association between the pattern and QDS. The classification accuracy
      is 83.5%, which keeps consistent with the accuracy obtained by the cross
      validation technique. The association between a symptom and the five biological
      parameters was established by the data mining method and it reached an accuracy
      of ~80%. These results showed that the t-test-based Adaboost algorithm might be a
      powerful technique for diagnosing syndrome in TCM in the context of CHD.

PMID- 21876711
TI  - The Ethanol Extract of Fructus trichosanthis Promotes Fetal Hemoglobin Production
      via p38 MAPK Activation and ERK Inactivation in K562 Cells.
AB  - Pharmacological stimulation of fetal hemoglobin (HbF) expression may be a
      promising approach for the treatment of beta-thalassemia. In this study, the
      effects of Fructus trichosanthis (FT) were investigated in human erythroleukemic
      K562 cells for their gamma-globin mRNA and HbF-induction activities. The role of
      signaling pathways, including extracellular regulated protein kinase (ERK) and
      p38 mitogen-activated protein kinase (MAPK), was also investigated. It was found
      that the ethanol extract of FT significantly increased gamma-globin mRNA and HbF
      levels, determined by real-time reverse transcription polymerase chain reaction
      and enzyme linked immunosorbent assay, respectively, in dose- and time-dependent
      manner. Total Hb (THb) levels were also elevated in the concentrations without
      cytotoxicity (<80 MUg mL(-1)). Pre-treatment with p38 MAPK inhibitor SB203580
      blocked the stimulatory effects of FT extract in total and HbF induction. In
      contrast, no change in HbF was observed when treated with ERK inhibitor PD98059.
      Furthermore, FT ethanol extract activated p38 MAPK and inhibited ERK signaling
      pathways in K562 cells, as revealed in western blotting analysis. In addition,
      SB203580 significantly abolished p38 MAPK activation when the cells were treated
      with FT. In summary, the ethanol extract of FT was found to be a potent inducer
      of HbF synthesis in K562 cells. The present data delineated the role of ERK and
      p38 MAPK signaling as molecular targets for pharmacologic stimulation of HbF
      production upon FT treatment.

PMID- 21876712
TI  - Role of Bone Morphogenetic Proteins-7 (BMP-7) in the Renal Improvement Effect of
      DangGui (Angelica sinensis) in Type-1 Diabetic Rats.
AB  - Hyperglycemia induced reactive oxygen species (ROS) generation is believed as
      major factors leading to diabetic nephropathy (DN). DangGui (Angelica sinensis)
      is mentioned to show renal protective effect in combination with other herbs.
      Bone morphogenetic proteins-7 (BMP-7) is produced merit in protection of DN. The
      role of BMP-7 in DangGui-induced renal improvement is not clear. The present
      study investigated the effects of DangGui on renal functions, BMP-7 expression
      and the levels of ROS in streptozotocin (STZ)-induced diabetic rats and high
      glucose-exposed rat mesangial cells (RMCs). After 1- or 4-week treatment, DangGui
      improved renal functions and increased renal BMP-7 expression in diabetic rats.
      The BMP-7 expression in RMCs was reduced by high glucose treatment and this could
      be reversed by DangGui. Moreover, RMCs exposed to high glucose were expired by
      BMP-7 RNAi transfection but those cells remained alive by scramble transfection.
      Thus, we employed regular RMCs to knock down BMP-7 with RNAi and we found that
      DangGui increased BMP-7 expression in these RMCs. Direct activation of BMP-7
      expression by DangGui could be considered. The results of DPPH assay, DHE stain
      and lucigenin assay indicated that DangGui could inhibit high glucose-induced ROS
      in RMCs. These results suggest that DangGui has an ability to improve renal
      functions in STZ-diabetic rats through increasing endogenous BMP-7 expression and
      decreasing oxidative stress in kidney. The present study suggest that DangGui
      could be applied to improve renal functions in diabetic disorders.

PMID- 21876713
TI  - The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast
      Cancer: An In Vitro and In Vivo Comparison Study with Herceptin.
AB  - HER-2 is an important oncoprotein overexpressed in about 15-25% of breast
      cancers. We hypothesized that the ability of curcumin to downregulate HER-2
      oncoprotein and inhibit the signal transduction pathway of PI3K/Akt, MAPK, and NF
      kappaB activation may be important in the treatment of HER-2-overexpressed breast
      cancer. To examine the effect of curcumin on breast cancer cells, MCF-7, MDA-MB
      231, MCF-10A, BT-474, and SK-BR-3-hr (a herceptin resistant strain from SK-BR-3)
      cells were used for in vitro analysis. The in vivo effect of curcumin on HER-2
      overexpressed breast cancer was investigated with the HER-2-overexpressed BT-474
      xenograft model. Cell growth, cell cycle change, the antimobility effect, signal
      transduction, and xenograft volume analysis between groups treated with herceptin
      and/or curcumin were tested. Curcumin decreased the cell growth of various breast
      cancer cell lines (MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr). In
      Western blot analysis, the phosphorylation of Akt, MAPK, and expression of NF
      kappaB were reduced in BT-474 cells, but not in SK-BR-3-hr cells, after treatment
      with herceptin. When treated with curcumin, the HER-2 oncoprotein,
      phosphorylation of Akt, MAPK and expression of NF-kappaB were decreased in both
      BT-474 and SK-BR-3-hr cells. In the BT-474 xenograft model, though not as much as
      herceptin, curcumin did effectively decrease the tumor size. The combination of
      curcumin with herceptin was not better than herceptin alone; however, the
      combination of taxol and curcumin had an antitumor effect comparable with taxol
      and herceptin. The results suggested that curcumin has potential as a treatment
      for HER-2-overexpressed breast cancer.

PMID- 21876714
TI  - Essential oils composition and antioxidant properties of three thymus species.
AB  - The essential oils of three wild-growing Thymus species, collected from west of
      Iran during the flowering stage, were obtained by hydrodistillation and analyzed
      by gas chromatography (GC) and gas chromatography/mass spectrometry (GC-MS).
      Under the optimum extraction and analysis conditions, 44, 38, and 38 constituents
      (mainly monoterpenes compounds) were identified in T. kotschyanus Boiss. and
      Hohen, T. eriocalyx (Ronniger) Jalas, and T. daenensis subsp lancifolius (Celak)
      Jalas which represented 89.9%, 99.7%, and 95.8% of the oils, respectively. The
      main constituents were thymol (16.4-42.6%), carvacrol (7.6-52.3%), and gamma
      terpinene (3-11.4%). Antioxidant activity was employed by two complementary test
      systems, namely, 2,2-diphenyl-1-picrylhydrazyl (DPPH) free-radical scavenging and
      beta-carotene/linoleic acid systems. Antioxidant activity of polar subfraction of
      T. daenensis subsp lancifolius (Celak) Jalas was found to be higher than those of
      the others in DPPH assay, while nonpolar subfraction of T. eriocalyx (Ronniger)
      Jalas has most antioxidant activity in beta-carotene/linoleic acid test (19.1 +/-
      0.1 MUg/mL and 96.1 +/- 0.8% inhibition rate, resp.).

PMID- 21876715
TI  - Electroacupuncture at PC6 (Neiguan) Improves Extracellular Signal-Regulated
      Kinase Signaling Pathways Through the Regulation of Neuroendocrine Cytokines in
      Myocardial Hypertrophic Rats.
AB  - Electroacupuncture (EA) therapy has been widely accepted as a useful therapeutic
      technique with low or no risk in the clinical prevention of cardiac hypertrophy.
      However, the signaling transduction mechanism underlying this effect remains
      unclear. The current study investigates the effects of EA on the signaling
      pathways of myocardial hypertrophy (MH) in rats. Up to 40 3-month-old Sprague
      Dawley (SD) rats were randomly divided into normal, model, PC6 (Neiguan), and LI4
      (Hegu) groups, with ten rats in each group. All the rats except for the normal
      group received 3 mg/kg.d of isoprinosine hydrochloride (ISO) injection into the
      back skin. The rats in the PC6 and LI4 groups received EA for 14 days. On the
      15th day, electrocardiograms were recorded, and the ultrastructure of the
      myocardial cells was observed. The myocardial hypertrophy indices (MHIs),
      electrocardiograph (ECG), ultrastructure observation, levels of plasma
      angiotensin II (Ang II) and endothelin (ET), as well as protein expression of
      extracellular signal-regulated kinase (ERK), and phosphorylation extracellular
      signal regulating kinase (p-ERK) in the left ventricular myocardial tissue were
      measured. The results indicated that EA can improve cardiac function in MH rats
      by modulating upstream neuroendocrine cytokines that regulate the ERK signaling
      pathways.

PMID- 21876717
TI  - Innate inflammation and cancer: Is it time for cancer prevention?
AB  - Recently, studies have been reported indicating that daily aspirin treatment for
      a period of 5 years or longer has a significant protective effect against death
      by colorectal carcinoma (as has previously been shown) and also against death by
      other solid cancers, both gastrointestinal and otherwise. These studies have
      reignited interest in the possibility of using nonsteroidal anti-inflammatory
      drugs for cancer prevention and the possibility that the numerous recent studies
      identifying the molecular mechanisms of the link between inflammation and cancer
      may allow the identification of better drugs for cancer prevention. Cancer often
      originates in tissues that are chronically inflamed, either in response to
      infections or noninfectious inflammation. Innate inflammation receptors,
      proinflammatory soluble factors, and inflammation-induced transcription factors
      have been identified that provide an understanding of some of the molecular
      pathways underlying the link between inflammation and cancer. However, the
      important role of the innate inflammatory pathways in host defense against
      pathogens and tissue damage as well as the maintenance of tissue integrity and
      homeostasis means that additional careful studies will be needed to identify anti
      inflammatory interventions with the beneficial effect of tumor prevention without
      unacceptable toxic side effects.

PMID- 21876716
TI  - 3,4-Dicaffeoylquinic Acid, a Major Constituent of Brazilian Propolis, Increases
      TRAIL Expression and Extends the Lifetimes of Mice Infected with the Influenza A
      Virus.
AB  - Brazilian green propolis water extract (PWE) and its chemical components,
      caffeoylquinic acids, such as 3,4-dicaffeoylquinic acid (3,4-diCQA), act against
      the influenza A virus (IAV) without influencing the viral components. Here, we
      evaluated the anti-IAV activities of these compounds in vivo. PWE or PEE
      (Brazilian green propolis ethanol extract) at a dose of 200 mg/kg was orally
      administered to Balb/c mice that had been inoculated with IAV strain A/WSN/33.
      The lifetimes of the PWE-treated mice were significantly extended compared to the
      untreated mice. Moreover, oral administration of 3,4-diCQA, a constituent of PWE,
      at a dose of 50 mg/kg had a stronger effect than PWE itself. We found that the
      amount of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) mRNA in
      the mice that were administered 3,4-diCQA was significantly increased compared to
      the control group, while H1N1 hemagglutinin (HA) mRNA was slightly decreased.
      These data indicate that PWE, PEE or 3,4-diCQA possesses a novel and unique
      mechanism of anti-influenza viral activity, that is, enhancing viral clearance by
      increasing TRAIL.

PMID- 21876718
TI  - Alloantigen-based AIDS vaccine: revisiting a "rightfully" discarded promising
      strategy.
AB  - This report revisits the accidental discovery that protection against simian
      immunodeficiency virus (SIV) infection in the early successful experimental AIDS
      vaccine studies in Rhesus macaques was due to antibodies directed against human
      leukocyte antigens (HLAs). The inactivated virus vaccine approach was discarded
      because protection was due to the host's immune reaction against the HLA acquired
      by SIV from the human cell lines in which it was grown, rather than against
      antigenic determinants of SIV itself. Subsequent studies have revealed that
      immune recognition of HLA on uninfected leukocytes also induces other factors
      that inhibit infection by both SIV and the human immunodeficiency virus. Pro and
      con aspects of immunization against HLA as a potential AIDS vaccine strategy are
      discussed.

PMID- 21876719
TI  - Vaccines for invasive fungal infections.
AB  - Morbidity and mortality from invasive fungal infections remain unacceptably high
      despite availability of new antifungal agents, underscoring the need for more
      effective preventative strategies. Due to our enhanced understanding of the host
      defense and pathogenetic mechanisms that lead to invasive fungal infections, it
      should be feasible to develop vaccines targeting these infections. A common
      immunological theme across many vaccine candidates for invasive fungal infections
      has been the need to activate a cell-based, pro-inflammatory, Th1 or Th17 immune
      response to improve phagocytic killing of the fungi. Since neutralization of
      virulence factor functions has not been required for many active vaccines to
      function, the antigenic repertoire available for testing should not be limited to
      virulence factors. With expansion of our fundamental understanding of the
      immunology of fungal infections, the biggest barrier to development of fungal
      vaccines is the lack of available capital to translate discoveries made at the
      bench into biological agents used at the bedside. Continued education on the
      importance and feasibility of vaccination for such infections, combined with
      continued development of vaccine antigens and adjuvants, is necessary.

PMID- 21876720
TI  - Emerging fungal infections in immunocompromised patients.
AB  - Invasive fungal infections are infections of importance and are increasing in
      incidence in immunocompromised hosts such as patients who have had hematopoietic
      stem cell and solid organ transplants. Despite our expanded antifungal
      armamentarium, these infections cause considerable morbidity and mortality.
      Indeed, certain trends have emerged in these invasive fungal infections: a rise
      in the incidence of invasive mold infections, an increase in the non-albicans
      strains of Candida spp. causing invasive disease and, finally, the emergence of
      less susceptible fungal strains that are resistant to the broader-spectrum
      antifungal agents due to overutilization of these agents. Clinicians must
      recognize the patient groups that are potentially at risk for these invasive
      fungal infections, as well as the risk factors for such infections. By using more
      sensitive nonculture-based diagnostic techniques, appropriate therapy may be
      initiated earlier to enhance survival in these immunocompromised patient
      populations.

PMID- 21876721
TI  - Pathobiology of acute pancreatitis: focus on intracellular calcium and
      calmodulin.
AB  - The exocrine pancreas synthesizes all the enzymes needed for intestinal breakdown
      of proteins, fats, and carbohydrates in our diet. Unfortunately, the proteases
      needed for the digestion of the meat we eat can, if inappropriately activated
      inside the acinar cells, also digest the pancreas itself as well as the
      surrounding tissues, which is what happens in the sometimes fatal human disease
      acute pancreatitis. The disease is currently untreatable, but significant
      progress has recently been made in understanding the fundamental processes
      initiating the pathological changes underlying pancreatic autodigestion. It is
      now clear that intracellular trypsin activation-a crucial step in pathogenesis-is
      due to excessive release of Ca(2+) from intracellular stores, principally via two
      types of inositol trisphosphate receptor. The unexpected recent discovery of an
      intrinsic protective mechanism caused by intracellular calmodulin and,
      specifically, the finding that this protective effect can be boosted by a
      membrane-permeable Ca(2+)-like peptide are promising.

PMID- 21876722
TI  - A history of optogenetics: the development of tools for controlling brain
      circuits with light.
AB  - Understanding how different kinds of neuron in the brain work together to
      implement sensations, feelings, thoughts, and movements, and how deficits in
      specific kinds of neuron result in brain diseases, has long been a priority in
      basic and clinical neuroscience. "Optogenetic" tools are genetically encoded
      molecules that, when targeted to specific neurons in the brain, enable their
      activity to be driven or silenced by light. These molecules are microbial opsins,
      seven-transmembrane proteins adapted from organisms found throughout the world,
      which react to light by transporting ions across the lipid membranes of cells in
      which they are genetically expressed. These tools are enabling the causal
      assessment of the roles that different sets of neurons play within neural
      circuits, and are accordingly being used to reveal how different sets of neurons
      contribute to the emergent computational and behavioral functions of the brain.
      These tools are also being explored as components of prototype neural control
      prosthetics capable of correcting neural circuit computations that have gone awry
      in brain disorders. This review gives an account of the birth of optogenetics and
      discusses the technology and its applications.

PMID- 21876723
TI  - Bacteria, food, and cancer.
AB  - Gut microbes are essential components of the human organism-helping us metabolize
      food into energy, produce micronutrients, and shape our immune systems. Having a
      particular pattern of gut microbes is also increasingly being linked to medical
      conditions including obesity, inflammatory bowel disease, and diabetes. Recent
      studies now indicate that our resident intestinal bacteria may also play a
      critical role in determining one's risk of developing cancer, ranging from
      protection against cancer to promoting its initiation and progression. Gut
      bacteria are greatly influenced by diet and in this review we explore evidence
      that they may be the missing piece that explains how dietary intake influences
      cancer risk, and discuss possible prevention and treatment strategies.

PMID- 21876724
TI  - Sweet memories: epigenetic control in flowering.
AB  - Many plants respond to winter with epigenetic factors that gradually dampen
      repression of flowering so that they can flower in spring. The study of this
      process was important for the identification of the plant Polycomb group (PcG) of
      proteins and their role in the epigenetic control of plant gene expression.
      Fittingly, these studies continue to illuminate our understanding of PcG
      function. We discuss recent advances, particularly the role of noncoding RNA in
      the recruitment of PcG to target genes, and the role of the PcG in regulating the
      stem cell pool in flowers.

PMID- 21876725
TI  - Valuing ecological systems and services.
AB  - Making trade-offs between ecological services and other contributors to human
      well-being is a difficult but critical process that requires valuation. This
      allows both better recognition of the ecological, social, and economic trade-offs
      and also allows us to bill those who use up or destroy ecological services and
      reward those that produce or enhance them. It also aids improved ecosystems
      policy. In this paper we clarify some of the controversies in defining the
      contributions to human well-being from functioning ecosystems, many of which
      people are not even aware of. We go on to describe the applicability of the
      various valuation methods that can be used in estimating the benefits of
      ecosystem services. Finally, we describe some recent case studies and lay out the
      research agenda for ecosystem services analysis, modeling, and valuation going
      forward.

PMID- 21876726
TI  - Exosomes: secreted vesicles and intercellular communications.
AB  - Exosomes are small membrane vesicles of endocytic origin secreted by most cell
      types, and are thought to play important roles in intercellular communications.
      Although exosomes were originally described in 1983, interest in these vesicles
      has really increased dramatically in the last 3 years, after the finding that
      they contain mRNA and microRNA. This discovery sparked renewed interest for the
      general field of membrane vesicles involved in intercellular communications, and
      research on these structures has grown exponentially over the last few years,
      probing their composition and function, as well as their potential value as
      biomarkers.

PMID- 21876727
TI  - Plant-soil interactions in a changing world.
AB  - Evidence is mounting to suggest that the transfer of carbon through roots of
      plants to the soil plays a primary role in regulating ecosystem responses to
      climate change and its mitigation. Future research is needed to improve
      understanding of the mechanisms involved in this phenomenon, its consequences for
      ecosystem carbon cycling, and the potential to exploit plant root traits and soil
      microbial processes that favor soil carbon sequestration.

PMID- 21876728
TI  - Harnessing the immune system's arsenal: producing human monoclonal antibodies for
      therapeutics and investigating immune responses.
AB  - Monoclonal antibody technology has undergone rapid and innovative reinvention
      over the last 30 years. Application of these technologies to human samples
      revealed valuable therapeutic and experimental insights. These technologies, each
      with their own benefits and flaws, have proven indispensable for immunological
      research and in our fight to provide new treatments and improved vaccines for
      infectious disease.

PMID- 21876729
TI  - PAX2 regulates ADAM10 expression and mediates anchorage-independent cell growth
      of melanoma cells.
AB  - PAX transcription factors play an important role during development and
      carcinogenesis. In this study, we investigated PAX2 protein levels in melanocytes
      and melanoma cells by Western Blot and immunofluorescence analysis and
      characterized the role of PAX2 in the pathogenesis of melanoma. In vitro we found
      weak PAX2 protein expression in keratinocytes and melanocytes. Compared to
      melanocytes increased PAX2 protein levels were detectable in melanoma cell lines.
      Interestingly, in tissue sections of melanoma patients nuclear PAX2 expression
      strongly correlated with nuclear atypia and the degree of prominent nucleoli,
      indicating an association of PAX2 with a more atypical cellular phenotype. In
      addition, with chromatin immunoprecipitation assay, PAX2 overexpression and PAX2
      siRNA we present compelling evidence that PAX2 can regulate ADAM10 expression, a
      metalloproteinase known to play important roles in melanoma metastasis. In human
      tissue samples we found co-expression of PAX2 and ADAM10 in melanocytes of benign
      nevi and in melanoma cells of patients with malignant melanoma. Importantly, the
      downregulation of PAX2 by specific siRNA inhibited the anchorage independent cell
      growth and decreased the migratory and invasive capacity of melanoma cells.
      Furthermore, the downregulation of PAX2 abrogated the chemoresistance of melanoma
      cells against cisplatin, indicating that PAX2 expression mediates cell survival
      and plays important roles during melanoma progression.

PMID- 21876730
TI  - Active electric imaging: body-object interplay and object's "electric texture".
AB  - This article deals with the role of fish's body and object's geometry on
      determining the image spatial shape in pulse Gymnotiforms. This problem was
      explored by measuring local electric fields along a line on the skin in the
      presence and absence of objects. We depicted object's electric images at
      different regions of the electrosensory mosaic, paying particular attention to
      the perioral region where a fovea has been described. When sensory surface
      curvature increases relative to the object's curvature, the image details
      depending on object's shape are blurred and finally disappear. The remaining
      effect of the object on the stimulus profile depends on the strength of its
      global polarization. This depends on the length of the object's axis aligned with
      the field, in turn depending on fish body geometry. Thus, fish's body and self
      generated electric field geometries are embodied in this "global effect" of the
      object. The presence of edges or local changes in impedance at the nearest
      surface of closely located objects adds peaks to the image profiles ("local
      effect" or "object's electric texture"). It is concluded that two cues for object
      recognition may be used by active electroreceptive animals: global effects
      (informing on object's dimension along the field lines, conductance, and
      position) and local effects (informing on object's surface). Since the field has
      fish's centered coordinates, and electrosensory fovea is used for exploration of
      surfaces, fish fine movements are essential to perform electric perception. We
      conclude that fish may explore adjacent objects combining active movements and
      electrogenesis to represent them using electrosensory information.

PMID- 21876731
TI  - Purification of tropomyosin, paramyosin, actin, tubulin, troponin and kinases for
      chemiproteomics and its application to different scientific fields.
AB  - BACKGROUND: p-aminobenzamidine (p-ABA) is used as a ligand in the purification of
      many serine proteases and in their removal from heterogeneous samples. Moreover,
      p-ABA has a potent ability to bind Ca(2+)-binding proteins. The binding ability
      and use of p-ABA in purification processes is still not fully understood.
      METHODOLOGY/PRINCIPAL FINDINGS: A p-Aminobenzamidine (p-ABA) ligand enabled the
      purification of the panallergenic proteins tropomyosin and paramyosin, as well as
      actin, tubulin, troponin and several kinases and annexins, with variable
      specificity depending on the tissue source and slight modifications to the
      purification process. The high affinity of p-ABA to tropomyosin, paramyosin,
      actin, troponin and myosin is calcium-dependent, since calcium regulates the
      function of these proteins. In addition, p-ABA probably simulates phosphorylated
      serine and therefore purified appropriate kinases. Because p-ABA binds to calcium
      dependent proteins, and probably those with binding sites containing serine, it
      is not a suitable inhibitor of proteolysis during the purification of such
      proteins. p-ABA is widely used to inhibit proteases during protein purification
      processes, but it is used in columns here to purify non-protease proteins. Two
      strategies were applied; the first was the inactivation of proteases that were
      not of interest using protease inhibitors. The second strategy employed was the
      use of a Ca(2+) wash solution to remove calcium-dependent proteins. The removal
      of calcium-dependent proteins from rabbit hind muscle pointed out even more
      selective purification. It is possible to obtain two purified samples: a) calcium
      dependent proteins and b) calcium independent proteins. Moreover, p-ABA may be
      useful as a model to study processes involving the phosphorylation of serine.
      CONCLUSION: A p-Aminobenzamidine (p-ABA) ligand enabled the purification of non
      protease proteins, with variable specificity depending on the tissue source and
      slight modifications to the purification process. The method is applicable to
      various scientific branches, but is especially practical for medicinal
      applications.

PMID- 21876732
TI  - Twinfilin-2a is dispensable for mouse development.
AB  - Twinfilins are evolutionarily conserved regulators of cytoskeletal dynamics. They
      inhibit actin polymerization by binding both actin monomers and filament barbed
      ends. Inactivation of the single twinfilin gene from budding yeast and fruit fly
      results in defects in endocytosis, cell migration, and organization of the
      cortical actin filament structures. Mammals express three twinfilin isoforms, of
      which twinfilin-1 and twinfilin-2a display largely overlapping expression
      patterns in non-muscle tissues of developing and adult mice. The expression of
      twinfilin-2b, which is generated through alternative promoter usage of the
      twinfilin-2 gene, is restricted to heart and skeletal muscles. However, the
      physiological functions of mammalian twinfilins have not been reported. As a
      first step towards understanding the function of twinfilin in vertebrates, we
      generated twinfilin-2a deficient mice by deleting exon 1 of the twinfilin-2 gene.
      Twinfilin-2a knockout mice developed normally to adulthood, were fertile, and did
      not display obvious morphological or behavioural abnormalities. Tissue anatomy
      and morphology in twinfilin-2a deficient mice was similar to that of wild-type
      littermates. These data suggest that twinfilin-2a plays a redundant role in
      cytoskeletal dynamics with the biochemically similar twinfilin-1, which is
      typically co-expressed in same tissues with twinfilin-2a.

PMID- 21876733
TI  - Protein-binding microarray analysis of tumor suppressor AP2alpha target gene
      specificity.
AB  - Cheap and massively parallel methods to assess the DNA-binding specificity of
      transcription factors are actively sought, given their prominent regulatory role
      in cellular processes and diseases. Here we evaluated the use of protein-binding
      microarrays (PBM) to probe the association of the tumor suppressor AP2alpha with
      6000 human genomic DNA regulatory sequences. We show that the PBM provides
      accurate relative binding affinities when compared to quantitative surface
      plasmon resonance assays. A PBM-based study of human healthy and breast tumor
      tissue extracts allowed the identification of previously unknown AP2alpha target
      genes and it revealed genes whose direct or indirect interactions with AP2alpha
      are affected in the diseased tissues. AP2alpha binding and regulation was
      confirmed experimentally in human carcinoma cells for novel target genes involved
      in tumor progression and resistance to chemotherapeutics, providing a molecular
      interpretation of AP2alpha role in cancer chemoresistance. Overall, we conclude
      that this approach provides quantitative and accurate assays of the specificity
      and activity of tumor suppressor and oncogenic proteins in clinical samples,
      interfacing genomic and proteomic assays.

PMID- 21876735
TI  - Genetic organisation, mobility and predicted functions of genes on integrated,
      mobile genetic elements in sequenced strains of Clostridium difficile.
AB  - BACKGROUND: Clostridium difficile is the leading cause of hospital-associated
      diarrhoea in the US and Europe. Recently the incidence of C. difficile-associated
      disease has risen dramatically and concomitantly with the emergence of
      'hypervirulent' strains associated with more severe disease and increased
      mortality. C. difficile contains numerous mobile genetic elements, resulting in
      the potential for a highly plastic genome. In the first sequenced strain, 630,
      there is one proven conjugative transposon (CTn), Tn5397, and six putative CTns
      (CTn1, CTn2 and CTn4-7), of which, CTn4 and CTn5 were capable of excision. In the
      second sequenced strain, R20291, two further CTns were described. RESULTS: CTn1,
      CTn2 CTn4, CTn5 and CTn7 were shown to excise from the genome of strain 630 and
      transfer to strain CD37. A putative CTn from R20291, misleadingly termed a phage
      island previously, was shown to excise and to contain three putative mobilisable
      transposons, one of which was capable of excision. In silico probing of C.
      difficile genome sequences with recombinase gene fragments identified new
      putative conjugative and mobilisable transposons related to the elements in
      strains 630 and R20291. CTn5-like elements were described occupying different
      insertion sites in different strains, CTn1-like elements that have lost the
      ability to excise in some ribotype 027 strains were described and one strain was
      shown to contain CTn5-like and CTn7-like elements arranged in tandem.
      Additionally, using bioinformatics, we updated previous gene annotations and
      predicted novel functions for the accessory gene products on these new elements.
      CONCLUSIONS: The genomes of the C. difficile strains examined contain highly
      related CTns suggesting recent horizontal gene transfer. Several elements were
      capable of excision and conjugative transfer. The presence of antibiotic
      resistance genes and genes predicted to promote adaptation to the intestinal
      environment suggests that CTns play a role in the interaction of C. difficile
      with its human host.

PMID- 21876734
TI  - The 3-hydroxy-2-butanone pathway is required for Pectobacterium carotovorum
      pathogenesis.
AB  - Pectobacterium species are necrotrophic bacterial pathogens that cause soft rot
      diseases in potatoes and several other crops worldwide. Gene expression data
      identified Pectobacterium carotovorum subsp. carotovorum budB, which encodes the
      alpha-acetolactate synthase enzyme in the 2,3-butanediol pathway, as more highly
      expressed in potato tubers than potato stems. This pathway is of interest because
      volatiles produced by the 2,3-butanediol pathway have been shown to act as plant
      growth promoting molecules, insect attractants, and, in other bacterial species,
      affect virulence and fitness. Disruption of the 2,3-butanediol pathway reduced
      virulence of P. c. subsp. carotovorum WPP14 on potato tubers and impaired
      alkalinization of growth medium and potato tubers under anaerobic conditions.
      Alkalinization of the milieu via this pathway may aid in plant cell maceration
      since Pectobacterium pectate lyases are most active at alkaline pH.

PMID- 21876736
TI  - Telomere length of circulating leukocyte subpopulations and buccal cells in
      patients with ischemic heart failure and their offspring.
AB  - BACKGROUND: We aimed to find support for the hypothesis that telomere length (TL)
      is causally involved in the pathogenesis of ischemic heart failure (IHF). We
      measured TL in IHF patients and their high-risk offspring and determined whether
      mean leukocyte TL reflects TL in CD34+ progenitor. We additionally measured TL of
      offspring of patients and controls to examine heritability throughout different
      cell types. METHODS AND RESULTS: TL was measured by qPCR in overall leukocytes,
      CD34+ progenitor cells, mononuclear cells (MNCs), and buccal cells in 27 IHF
      patients, 24 healthy controls and 60 offspring. TL in IHF patients was shorter
      than healthy controls in leukocytes (p = 0.002), but not in CD34+ cells (p =
      0.39), MNCs (p = 0.31) or buccal cells (p = 0.19). Offspring of IHF patients had
      shorter TL in leukocytes than offspring of healthy subjects (p = 0.04) but not in
      other cell types. Controls and offspring showed a good within person correlation
      between leukocytes and CD34+ cells (r 0.562; p = 0.004 and r 0.602; p = 0.001,
      respectively). In IHF patients and offspring the correlation among cell types was
      blunted. Finally, we found strong correlations between parent and offspring TL in
      all four cell types. CONCLUSIONS: Reduced leukocyte TL in offspring of IHF
      subjects suggests a potential causal link of TL in ischemic heart disease.
      However, this causality is unlikely to originate from exhaustion of TL in CD34+
      progenitor or MNC cells as their lengths are not well captured by overall
      leukocyte TL. Additionally, we found strong correlations between parent and
      offspring TL in all examined cell types, suggesting high heritability of TL among
      cell types.

PMID- 21876737
TI  - Subinhibitory arsenite concentrations lead to population dispersal in Thiomonas
      sp.
AB  - Biofilms represent the most common microbial lifestyle, allowing the survival of
      microbial populations exposed to harsh environmental conditions. Here, we show
      that the biofilm development of a bacterial species belonging to the Thiomonas
      genus, frequently found in arsenic polluted sites and playing a key role in
      arsenic natural remediation, is markedly modified when exposed to subinhibitory
      doses of this toxic element. Indeed, arsenite [As(III)] exposure led to a
      considerable impact on biofilm maturation by strongly increasing the
      extracellular matrix synthesis and by promoting significant cell death and lysis
      within microcolonies. These events were followed by the development of complex 3D
      biofilm structures and subsequently by the dispersal of remobilized cells
      observed inside the previously formed hollow voids. Our results demonstrate that
      this biofilm community responds to arsenite stress in a multimodal way, enhancing
      both survival and dispersal. Addressing this complex bacterial response to
      As(III) stress, which might be used by other microorganisms under various adverse
      conditions, may be essential to understand how Thiomonas strains persist in
      extreme environments.

PMID- 21876738
TI  - CD40 is essential in the upregulation of TRAF proteins and NF-kappaB-dependent
      proinflammatory gene expression after arterial injury.
AB  - Despite extensive investigations, restenosis, which is characterized primarily by
      neointima formation, remains an unsolved clinical problem after vascular
      interventions. A recent study has shown that CD40 signaling through TNF receptor
      associated factor 6 (TRAF6) plays a key role in neointima formation after carotid
      artery injury; however, underlying mechanisms are not clearly elucidated. Because
      neointima formation may vary significantly depending on the type of injury, we
      first assessed the effect of CD40 deficiency on neointima formation in 2 injury
      models, carotid artery ligation and femoral artery denudation injury. Compared
      with wild-type mice, CD40 deficiency significantly reduced neointima formation
      and lumen stenosis in two different models. Further, we investigated the
      mechanism by which CD40 signaling affects neointima formation after arterial
      injury. In wild-type mice, the expression levels of CD40, several TRAF proteins,
      including TRAF1, TRAF2, TRAF3, TRAF5, and TRAF6, as well as total NF-kB p65 and
      phospho-NF-kB p65, in the carotid artery were markedly upregulated within 3-7
      days after carotid ligation. Deficiency of CD40 abolished the injury-induced
      upregulation of TRAFs including TRAF6 and NF-kB-p65 in the injured vessel wall.
      Further, CD40(-/-) mice showed a significant decrease in the recruitment of
      neutrophils (at 3, 7d) and macrophages (at 7, 21d) into injured artery; this
      effect was most likely attributed to inhibition of NF-kB activation and marked
      downregulation of NF-kB-related gene expression, including cytokines (TNFalpha,
      IL-1beta, IL-6), chemokines (MCP-1), and adhesion molecules (ICAM-1, VCAM-1).
      Moreover, neutrophil recruitment in a model of thioglycollate-induced peritonitis
      is impaired in CD40-deficient mice. In vitro data revealed that CD40 deficiency
      blocked CD40L-induced NF-kB p65 nuclear translocation in leukocytes. Altogether,
      our data identified for the first time that CD40 is essential in the upregulation
      of TRAF6, NF-kB activation, and NF-kB-dependent proinflammatory genes in vivo.
      Our findings firmly established the role for CD40 in neointima formation in 2
      distinct injury models.

PMID- 21876739
TI  - Optimised and rapid pre-clinical screening in the SOD1(G93A) transgenic mouse
      model of amyotrophic lateral sclerosis (ALS).
AB  - The human SOD1(G93A) transgenic mouse has been used extensively since its
      development in 1994 as a model for amyotrophic lateral sclerosis (ALS). In that
      time, a great many insights into the toxicity of mutant SOD1 have been gained
      using this and other mutant SOD transgenic mouse models. They all demonstrate a
      selective toxicity towards motor neurons and in some cases features of the
      pathology seen in the human disease. These models have two major drawbacks.
      Firstly the generation of robust preclinical data in these models has been
      highlighted as an area for concern. Secondly, the amount of time required for a
      single preclinical experiment in these models (3-4 months) is a hurdle to the
      development of new therapies. We have developed an inbred C57BL/6 mouse line from
      the original mixed background (SJLxC57BL/6) SOD1(G93A) transgenic line and show
      here that the disease course is remarkably consistent and much less prone to
      background noise, enabling reduced numbers of mice for testing of therapeutics.
      Secondly we have identified very early readouts showing a large decline in motor
      function compared to normal mice. This loss of motor function has allowed us to
      develop an early, sensitive and rapid screening protocol for the initial phases
      of denervation of muscle fibers, observed in this model. We describe multiple,
      quantitative readouts of motor function that can be used to interrogate this
      early mechanism. Such an approach will increase throughput for reduced costs,
      whilst reducing the severity of the experimental procedures involved.

PMID- 21876740
TI  - Wide distribution of O157-antigen biosynthesis gene clusters in Escherichia coli.
AB  - Most Escherichia coli O157-serogroup strains are classified as enterohemorrhagic
      E. coli (EHEC), which is known as an important food-borne pathogen for humans.
      They usually produce Shiga toxin (Stx) 1 and/or Stx2, and express H7-flagella
      antigen (or nonmotile). However, O157 strains that do not produce Stxs and
      express H antigens different from H7 are sometimes isolated from clinical and
      other sources. Multilocus sequence analysis revealed that these 21 O157:non-H7
      strains tested in this study belong to multiple evolutionary lineages different
      from that of EHEC O157:H7 strains, suggesting a wide distribution of the gene set
      encoding the O157-antigen biosynthesis in multiple lineages. To gain insight into
      the gene organization and the sequence similarity of the O157-antigen
      biosynthesis gene clusters, we conducted genomic comparisons of the chromosomal
      regions (about 59 kb in each strain) covering the O-antigen gene cluster and its
      flanking regions between six O157:H7/non-H7 strains. Gene organization of the
      O157-antigen gene cluster was identical among O157:H7/non-H7 strains, but was
      divided into two distinct types at the nucleotide sequence level. Interestingly,
      distribution of the two types did not clearly follow the evolutionary lineages of
      the strains, suggesting that horizontal gene transfer of both types of O157
      antigen gene clusters has occurred independently among E. coli strains.
      Additionally, detailed sequence comparison revealed that some positions of the
      repetitive extragenic palindromic (REP) sequences in the regions flanking the O
      antigen gene clusters were coincident with possible recombination points. From
      these results, we conclude that the horizontal transfer of the O157-antigen gene
      clusters induced the emergence of multiple O157 lineages within E. coli and
      speculate that REP sequences may involve one of the driving forces for exchange
      and evolution of O-antigen loci.

PMID- 21876741
TI  - Insightful problem solving in an Asian elephant.
AB  - The "aha" moment or the sudden arrival of the solution to a problem is a common
      human experience. Spontaneous problem solving without evident trial and error
      behavior in humans and other animals has been referred to as insight.
      Surprisingly, elephants, thought to be highly intelligent, have failed to exhibit
      insightful problem solving in previous cognitive studies. We tested whether three
      Asian elephants (Elephas maximus) would use sticks or other objects to obtain
      food items placed out-of-reach and overhead. Without prior trial and error
      behavior, a 7-year-old male Asian elephant showed spontaneous problem solving by
      moving a large plastic cube, on which he then stood, to acquire the food. In
      further testing he showed behavioral flexibility, using this technique to reach
      other items and retrieving the cube from various locations to use as a tool to
      acquire food. In the cube's absence, he generalized this tool utilization
      technique to other objects and, when given smaller objects, stacked them in an
      attempt to reach the food. The elephant's overall behavior was consistent with
      the definition of insightful problem solving. Previous failures to demonstrate
      this ability in elephants may have resulted not from a lack of cognitive ability
      but from the presentation of tasks requiring trunk-held sticks as potential
      tools, thereby interfering with the trunk's use as a sensory organ to locate the
      targeted food.

PMID- 21876742
TI  - An inserted alpha/beta subdomain shapes the catalytic pocket of Lactobacillus
      johnsonii cinnamoyl esterase.
AB  - BACKGROUND: Microbial enzymes produced in the gastrointestinal tract are
      primarily responsible for the release and biochemical transformation of
      absorbable bioactive monophenols. In the present work we described the crystal
      structure of LJ0536, a serine cinnamoyl esterase produced by the probiotic
      bacterium Lactobacillus johnsonii N6.2. METHODOLOGY/PRINCIPAL FINDINGS: We
      crystallized LJ0536 in the apo form and in three substrate-bound complexes. The
      structure showed a canonical alpha/beta fold characteristic of esterases, and the
      enzyme is dimeric. Two classical serine esterase motifs (GlyXSerXGly) can be
      recognized from the amino acid sequence, and the structure revealed that the
      catalytic triad of the enzyme is formed by Ser(106), His(225), and Asp(197),
      while the other motif is non-functional. In all substrate-bound complexes, the
      aromatic acyl group of the ester compound was bound in the deepest part of the
      catalytic pocket. The binding pocket also contained an unoccupied area that could
      accommodate larger ligands. The structure revealed a prominent inserted
      alpha/beta subdomain of 54 amino acids, from which multiple contacts to the
      aromatic acyl groups of the substrates are made. Inserts of this size are seen in
      other esterases, but the secondary structure topology of this subdomain of LJ0536
      is unique to this enzyme and its closest homolog (Est1E) in the Protein Databank.
      CONCLUSIONS: The binding mechanism characterized (involving the inserted
      alpha/beta subdomain) clearly differentiates LJ0536 from enzymes with similar
      activity of a fungal origin. The structural features herein described together
      with the activity profile of LJ0536 suggest that this enzyme should be clustered
      in a new group of bacterial cinnamoyl esterases.

PMID- 21876743
TI  - Prognostic significance of miR-181b and miR-21 in gastric cancer patients treated
      with S-1/Oxaliplatin or Doxifluridine/Oxaliplatin.
AB  - BACKGROUND: The goal of this study is to evaluate the effectiveness of S
      1/Oxaliplatin vs. Doxifluridine/Oxaliplatin regimen and to identify miRNAs as
      potential prognostic biomarkers in gastric cancer patients. The expression of
      candidate miRNAs was quantified from fifty-five late stage gastric cancer FFPE
      specimens. EXPERIMENTAL DESIGN: Gastric cancer patients with KPS>70 were
      recruited for the trial. The control group was treated with 400 mg/twice/day
      Doxifluridine plus i.v. with Oxaliplatin at 130 mg/m(2)/first day/4 week cycle.
      The testing group was treated with S-1 at 40 mg/twice/day/4 week cycle plus i.v.
      with Oxaliplatin at 130 mg/m(2)/first day/4 week cycle. Total RNAs were extracted
      from normal and gastric tumor specimens. The levels of miRNAs were quantified
      using real time qRT-PCR expression analysis. RESULTS: The overall objective
      response rate (CR+PR) of patients treated with S-1/Oxaliplatin was 33.3% (CR+PR)
      vs. 17.6% (CR+PR) with Doxifluridine/Oxaliplatin for advanced stage gastric
      cancer patients. The average overall survival for patients treated with S
      1/Oxaliplatin was 7.80 month vs. 7.30 month with patients treated with
      Doxifluridine/Oxaliplatin. The expression of miR-181b (P = 0.022) and miR-21 (P =
      0.0029) was significantly overexpressed in gastric tumors compared to normal
      gastric tissues. Kaplan-Meier survival analysis revealed that low levels of miR
      21 expression (Log rank test, hazard ratio: 0.17, CI = 0.06-0.45; P = 0.0004) and
      miR-181b (Log rank test, hazard ratio: 0.37, CI = 0.16-0.87; P = 0.018) are
      closely associated with better patient's overall survival for both S-1 and
      Doxifluridine based regimens. CONCLUSION: Patients treated with S-1/Oxaliplatin
      had a better response than those treated with Doxifluridine/Oxaliplatin. miR-21
      and miR-181b hold great potential as prognostic biomarkers in late stage gastric
      cancer.

PMID- 21876744
TI  - BAAV mediated GJB2 gene transfer restores gap junction coupling in cochlear
      organotypic cultures from deaf Cx26Sox10Cre mice.
AB  - The deafness locus DFNB1 contains GJB2, the gene encoding connexin26 and GJB6,
      encoding connexin30, which appear to be coordinately regulated in the inner ear.
      In this work, we investigated the expression and function of connexin26 and
      connexin30 from postnatal day 5 to adult age in double transgenic Cx26(Sox10Cre)
      mice, which we obtained by crossing connexin26 floxed mice with a deleter Sox10
      Cre line. Cx26(Sox10Cre) mice presented with complete connexin26 ablation in the
      epithelial gap junction network of the cochlea, whereas connexin30 expression was
      developmentally delayed; immunolabeling patterns for both connexins were normal
      in the cochlear lateral wall. In vivo electrophysiological measurements in
      Cx26(Sox10Cre) mice revealed profound hearing loss accompanied by reduction of
      endocochlear potential, and functional experiments performed in postnatal
      cochlear organotypic cultures showed impaired gap junction coupling. Transduction
      of these cultures with a bovine adeno associated virus vector restored connexin26
      protein expression and rescued gap junction coupling. These results suggest that
      restoration of normal connexin levels by gene delivery via recombinant adeno
      associated virus could be a way to rescue hearing function in DFNB1 mouse models
      and, in future, lead to the development of therapeutic interventions in humans.

PMID- 21876745
TI  - Comparison of the 'Ca. Liberibacter asiaticus' genome adapted for an
      intracellular lifestyle with other members of the Rhizobiales.
AB  - An intracellular plant pathogen 'Candidatus Liberibacter asiaticus,' a member of
      the Rhizobiales, is related to Sinorhizobium meliloti, Bradyrhizobium japonicum,
      nitrogen fixing endosymbionts, Agrobacterium tumefaciens, a plant pathogen, and
      Bartonella henselae, an intracellular mammalian pathogen. Whole chromosome
      comparisons identified at least 50 clusters of conserved orthologous genes found
      on the chromosomes of all five metabolically diverse species. The intracellular
      pathogens 'Ca. Liberibacter asiaticus' and Bartonella henselae have genomes
      drastically reduced in gene content and size as well as a relatively low content
      of guanine and cytosine. Codon and amino acid preferences that emphasize low
      guanosine and cytosine usage are globally employed in these genomes, including
      within regions of microsynteny and within signature sequences of orthologous
      proteins. The length of orthologous proteins is generally conserved, but not
      their isoelectric points, consistent with extensive amino acid substitutions to
      accommodate selection for low GC content. The 'Ca. Liberibacter asiaticus' genome
      apparently has all of the genes required for DNA replication present in
      Sinorhizobium meliloti except it has only two, rather than three RNaseH genes.
      The gene set required for DNA repair has only one rather than ten DNA ligases
      found in Sinorhizobium meliloti, and the DNA PolI of 'Ca. Liberibacter asiaticus'
      lacks domains needed for excision repair. Thus the ability of 'Ca. Liberibacter
      asiaticus' to repair mutations in its genome may be impaired. Both 'Ca.
      Liberibacter asiaticus and Bartonella henselae lack enzymes needed for the
      metabolism of purines and pyrimidines, which must therefore be obtained from the
      host. The 'Ca. Liberibacter asiaticus' genome also has a greatly reduced set of
      sigma factors used to control transcription, and lacks sigma factors 24, 28 and
      38. The 'Ca. Liberibacter asiaticus' genome has all of the hallmarks of a reduced
      genome of a pathogen adapted to an intracellular lifestyle.

PMID- 21876746
TI  - Phosphorylated CpxR restricts production of the RovA global regulator in Yersinia
      pseudotuberculosis.
AB  - BACKGROUND: RovA is a global transcriptional regulator of gene expression in
      pathogenic Yersinia. RovA levels are kept in check by a sophisticated layering of
      distinct transcriptional and post-transcriptional regulatory mechanisms. In the
      enteropathogen Y. pseudotuberculosis, we have previously reported that the
      extracytoplasmic stress sensing CpxA-CpxR two-component regulatory system
      modulates rovA expression. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we
      characterized CpxR phosphorylation (CpxR~P) in vitro, and determined that
      phosphorylation was necessary for CpxR to efficiently bind to the PCR-amplified
      upstream regulatory region of rovA. The precise CpxR~P binding site was mapped by
      a nuclease protection assay and directed mutagenesis confirmed that in vivo
      binding to the rovA promoter inhibits transcription. Reduced RovA production was
      most pronounced following CpxR~P accumulation in the Yersinia cytoplasm during
      chronic Cpx pathway activation and by the indiscriminate phosphodonor action of
      acetyl phosphate. CONCLUSIONS/SIGNIFICANCE: Cpx pathway activation restricts
      levels of the RovA global regulator. The regulatory influence of CpxR~P must
      therefore extend well beyond periplasmic quality control in the Yersinia
      envelope, to include genes involved in environmental survival and pathogenicity.

PMID- 21876748
TI  - Neurodegenerative properties of chronic pain: cognitive decline in patients with
      chronic pancreatitis.
AB  - Chronic pain has been associated with impaired cognitive function. We examined
      cognitive performance in patients with severe chronic pancreatitis pain. We
      explored the following factors for their contribution to observed cognitive
      deficits: pain duration, comorbidity (depression, sleep disturbance), use of
      opioids, and premorbid alcohol abuse. The cognitive profiles of 16 patients with
      severe pain due to chronic pancreatitis were determined using an extensive
      neuropsychological test battery. Data from three cognitive domains (psychomotor
      performance, memory, executive functions) were compared to data from healthy
      controls matched for age, gender and education. Multivariate multilevel analysis
      of the data showed decreased test scores in patients with chronic pancreatitis
      pain in different cognitive domains. Psychomotor performance and executive
      functions showed the most prominent decline. Interestingly, pain duration
      appeared to be the strongest predictor for observed cognitive decline. Depressive
      symptoms, sleep disturbance, opioid use and history of alcohol abuse provided
      additional explanations for the observed cognitive decline in some of the tests,
      but to a lesser extent than pain duration. The negative effect of pain duration
      on cognitive performance is compatible with the theory of neurodegenerative
      properties of chronic pain. Therefore, early and effective therapeutic
      interventions might reduce or prevent decline in cognitive performance, thereby
      improving outcomes and quality of life in these patients.

PMID- 21876747
TI  - Licensing virus-specific T cells to secrete the neutrophil attracting chemokine
      CXCL-8 during hepatitis B virus infection.
AB  - T cell functional plasticity helps tailor antiviral immunity during different
      phases of infections. We tested whether, during different phases of HBV
      infection, virus-specific T cells can acquire specific proinflammatory functions
      that could drive granulocyte/mononuclear cell liver infiltration. Multifunctional
      analysis of HBV-specific T cells during acute and chronic HBV infection revealed
      that HBV-specific T cells had the capacity to produce the neutrophil chemokine
      CXCL-8 but not IL-17. CXCL-8 producing T cells were detectable in the liver of
      chronic HBV patients with active hepatitis; while in acute HBV patients CXCL-8
      production by T cells was temporally limited to the acute phase of disease,
      concomitant with the peak of liver inflammation. Characterization of the
      conditions necessary for the development of CXCL-8 producing T cells showed a
      requirement for IL-7 and IL-15 during T cell expansion. These data show that
      functional plasticity of virus-specific T cells spontaneously occurs during HBV
      infection and that an environment rich IL-7 and IL-15 can license T cells with
      the ability to produce CXCL-8 and potentially influence liver pathology.

PMID- 21876749
TI  - Phagocytic activity is impaired in type 2 diabetes mellitus and increases after
      metabolic improvement.
AB  - OBJECTIVE: 1) To evaluate whether peripheral blood mononuclear cells (PBMCs) from
      type 2 diabetic patients present an impairment of phagocytic activity; 2) To
      determine whether the eventual impairment in phagocytic activity is related to
      glycemic control and can be reversed by improving blood glucose levels. METHODS:
      21 type 2 diabetic patients and 21 healthy volunteers were prospectively
      recruited for a case-control study. In addition, those patients in whom HbA1c was
      higher than 8% (n = 12) were hospitalized in order to complete a 5-day
      intensification treatment of blood glucose. Phagocytic activity was assessed by
      using a modified flow cytometry procedure developed in our laboratory based on
      DNA/RNA viable staining to discriminate erythrocytes and debris. This method is
      simple, highly sensitive and reproducible and it takes advantage of classic
      methods that are widely used in flow cytometry. RESULTS: Type 2 diabetic patients
      showed a lower percentage of activated macrophages in comparison with non
      diabetic subjects (54.00+/-18.93 vs 68.53+/-12.77%; p = 0.006) Significant
      negative correlations between phagocytic activity and fasting glucose (r = 
      0.619, p = 0.004) and HbA1c (r = -0.506, p = 0.019) were detected. In addition,
      multiple linear regression analyses showed that either fasting plasma glucose or
      HbA1c were independently associated with phagocytic activity. Furthermore, in the
      subset of patients who underwent metabolic optimization a significant increase in
      phagocytic activity was observed (p = 0.029). CONCLUSIONS: Glycemic control is
      related to phagocytic activity in type 2 diabetes. Our results suggest that
      improvement in phagocytic activity can be added to the beneficial effects of
      metabolic optimization.

PMID- 21876750
TI  - Wdr18 is required for Kupffer's vesicle formation and regulation of body
      asymmetry in zebrafish.
AB  - Correct specification of the left-right (L-R) axis is important for organ
      morphogenesis. Conserved mechanisms involving cilia rotation inside node-like
      structures and asymmetric Nodal signaling in the lateral plate mesoderm (LPM),
      which are important symmetry-breaking events, have been intensively studied. In
      zebrafish, the clustering and migration of dorsal forerunner cells (DFCs) is
      critical for the formation of the Kuppfer's vesicle (KV). However, molecular
      events underlying DFC clustering and migration are less understood. The WD-repeat
      proteins function in a variety of biological processes, including cytoskeleton
      assembly, intracellular trafficking, mRNA splicing, transcriptional regulation
      and cell migration. However, little is known about the function of WD-repeat
      proteins in L-R asymmetry determination. Here, we report the identification and
      functional analyses of zebrafish wdr18, a novel gene that encodes a WD-repeat
      protein that is highly conserved among vertebrate species. wdr18 was identified
      from a Tol2 transposon-mediated enhancer trap screen. Follow-up analysis of wdr18
      mRNA expression showed that it was detected in DFCs or the KV progenitor cells
      and later in the KV at early somitogenesis stages. Morpholino knockdown of wdr18
      resulted in laterality defects in the visceral organs, which were preceded by the
      mis-expression of Nodal-related genes, including spaw and pitx2. Examination of
      morphants at earlier stages revealed that the KV had fewer and shorter cilia
      which are immotile and a smaller cavity. We further investigated the organization
      of DFCs in wdr18 morphant embryos using ntl and sox17 as specific markers and
      found that the clustering and migration of DFC was altered, leading to a
      disorganized KV. Finally, through a combination of wdr18 and itgb1b morpholino
      injections, we provided evidence that wdr18 and itgb1b genetically interact in
      the laterality determination process. Thus, we reveal a new and essential role
      for WD-repeat proteins in the determination and regulation of L-R asymmetry and
      propose a potential mechanism for wdr18 in the regulation of DFC clustering and
      migration and KV formation.

PMID- 21876751
TI  - Killing hypoxic cell populations in a 3D tumor model with EtNBS-PDT.
AB  - An outstanding problem in cancer therapy is the battle against treatment
      resistant disease. This is especially true for ovarian cancer, where the majority
      of patients eventually succumb to treatment-resistant metastatic carcinomatosis.
      Limited perfusion and diffusion, acidosis, and hypoxia play major roles in the
      development of resistance to the majority of front-line therapeutic regimens. To
      overcome these limitations and eliminate otherwise spared cancer cells, we
      utilized the cationic photosensitizer EtNBS to treat hypoxic regions deep inside
      in vitro 3D models of metastatic ovarian cancer. Unlike standard regimens that
      fail to penetrate beyond ~150 um, EtNBS was found to not only penetrate
      throughout the entirety of large (>200 um) avascular nodules, but also
      concentrate into the nodules' acidic and hypoxic cores. Photodynamic therapy with
      EtNBS was observed to be highly effective against these hypoxic regions even at
      low therapeutic doses, and was capable of destroying both normoxic and hypoxic
      regions at higher treatment levels. Imaging studies utilizing multiphoton and
      confocal microscopies, as well as time-lapse optical coherence tomography (TL
      OCT), revealed an inside-out pattern of cell death, with apoptosis being the
      primary mechanism of cell killing. Critically, EtNBS-based photodynamic therapy
      was found to be effective against the model tumor nodules even under severe
      hypoxia. The inherent ability of EtNBS photodynamic therapy to impart
      cytotoxicity across a wide range of tumoral oxygenation levels indicates its
      potential to eliminate treatment-resistant cell populations.

PMID- 21876752
TI  - DNA extraction columns contaminated with murine sequences.
AB  - Sequences of the novel gammaretrovirus, xenotropic murine leukemia virus-related
      virus (XMRV) have been described in human prostate cancer tissue, although the
      amounts of DNA are low. Furthermore, XMRV sequences and polytropic (p) murine
      leukemia viruses (MLVs) have been reported in patients with chronic fatigue
      syndrome (CFS). In assessing the prevalence of XMRV in prostate cancer tissue
      samples we discovered that eluates from naive DNA purification columns, when
      subjected to PCR with primers designed to detect genomic mouse DNA contamination,
      occasionally gave rise to amplification products. Further PCR analysis, using
      primers to detect XMRV, revealed sequences derived from XMRV and pMLVs from mouse
      and human DNA and DNA of unspecified origin. Thus, DNA purification columns can
      present problems when used to detect minute amounts of DNA targets by highly
      sensitive amplification techniques.

PMID- 21876753
TI  - The use of serum glial fibrillary acidic protein measurements in the diagnosis of
      neuromyelitis optica spectrum optic neuritis.
AB  - BACKGROUND: Glial fibrillary acidic protein (GFAP) is a specific intermediate
      filament of the cytoskeleton of the astrocyte and may be used as a specific
      marker for astrocytic damage. It is detectable in the cerebrospinal fluid
      following a relapse caused by Multiple Sclerosis (MS) and Neuromyelitis Optica
      (NMO) spectrum disease. Higher levels are found following an NMO-related relapse.
      It is not known if GFAP is also detectable in the serum following such relapses.
      In particular, it is not known if lesions limited to the optic nerve release GFAP
      in sufficient quantities to be detectable within the serum. The aim of this study
      was to ascertain the extent to which serum GFAP levels can distinguish between an
      episode of optic neuritis (ON) related to NMO spectrum disease and ON from other
      causes. METHODOLOGY/PRINCIPAL FINDINGS: Out of 150 patients consecutively
      presenting to our eye hospital over the period March 2009 until July 2010, we
      were able to collect a serum sample from 12 patients who had presented with MS
      related ON and from 10 patients who had presented with NMO spectrum disease
      related ON. We also identified 8 patients with recurrent isolated ON and 8
      patients with a corticosteroid-dependent optic neuropathy in the absence of any
      identified aetiology. GFAP was detectable in the serum of all but three patients
      (two patients with MS-related ON and one with recurrent optic neuritis). The
      median serum GFAP level in the patient group with NMO spectrum disease was 4.63
      pg/mL whereas in all other cases combined together, this was 2.14 pg/mL. The
      difference was statistically significant (P = 0.01). A similar statistically
      significant difference was found when cases with pathology limited to the optic
      nerve were compared (P = 0.03). CONCLUSIONS: Glial pathology in NMO related optic
      neuritis is reflected in elevated serum GFAP levels independently of whether or
      not there is extra-optic nerve disease.

PMID- 21876754
TI  - Meraculous: de novo genome assembly with short paired-end reads.
AB  - We describe a new algorithm, meraculous, for whole genome assembly of deep paired
      end short reads, and apply it to the assembly of a dataset of paired 75-bp
      Illumina reads derived from the 15.4 megabase genome of the haploid yeast Pichia
      stipitis. More than 95% of the genome is recovered, with no errors; half the
      assembled sequence is in contigs longer than 101 kilobases and in scaffolds
      longer than 269 kilobases. Incorporating fosmid ends recovers entire chromosomes.
      Meraculous relies on an efficient and conservative traversal of the subgraph of
      the k-mer (deBruijn) graph of oligonucleotides with unique high quality
      extensions in the dataset, avoiding an explicit error correction step as used in
      other short-read assemblers. A novel memory-efficient hashing scheme is
      introduced. The resulting contigs are ordered and oriented using paired reads
      separated by ~280 bp or ~3.2 kbp, and many gaps between contigs can be closed
      using paired-end placements. Practical issues with the dataset are described, and
      prospects for assembling larger genomes are discussed.

PMID- 21876755
TI  - The astrocyte-targeted therapy by Bushi for the neuropathic pain in mice.
AB  - BACKGROUND: There is accumulating evidence that the activation of spinal glial
      cells, especially microglia, is a key event in the pathogenesis of neuropathic
      pain. However, the inhibition of microglial activation is often ineffective,
      especially for long-lasting persistent neuropathic pain. So far, neuropathic pain
      remains largely intractable and a new therapeutic strategy for the pain is still
      required. METHODS/PRINCIPAL FINDINGS: Using Seltzer model mice, we investigated
      the temporal aspect of two types of neuropathic pain behaviors, i.e., thermal
      hyperalgesia and mechanical allodynia, as well as that of morphological changes
      in spinal microglia and astrocytes by immunohistochemical studies. Firstly, we
      analyzed the pattern of progression in the pain behaviors, and found that the
      pain consisted of an "early induction phase" and subsequent "late maintenance
      phase". We next analyzed the temporal changes in spinal glial cells, and found
      that the induction and the maintenance phase of pain were associated with the
      activation of microglia and astrocytes, respectively. When Bushi, a Japanese
      herbal medicine often used for several types of persistent pain, was administered
      chronically, it inhibited the maintenance phase of pain without affecting the
      induction phase, which was in accordance with the inhibition of astrocytic
      activation in the spinal cord. These analgesic effects and the inhibition of
      astrocytic activation by Bushi were mimicked by the intrathecal injection of
      fluorocitrate, an inhibitor of astrocytic activation. Finally, we tested the
      direct effect of Bushi on astrocytic activation, and found that Bushi suppressed
      the IL-1beta- or IL-18-evoked ERK1/2-phosphorylation in cultured astrocytes but
      not the ATP-evoked p38- and ERK1/2-phosphorylation in microglia in vitro.
      CONCLUSIONS: Our results indicated that the activation of spinal astrocytes was
      responsible for the late maintenance phase of neuropathic pain in the Seltzer
      model mice and, therefore, the inhibition of astrocytic activation by Bushi could
      be a useful therapeutic strategy for treating neuropathic pain.

PMID- 21876756
TI  - Prostaglandin E2 promotes endothelial differentiation from bone marrow-derived
      cells through AMPK activation.
AB  - Prostaglandin E2 (PGE2) has been reported to modulate angiogenesis, the process
      of new blood vessel formation, by promoting proliferation, migration and tube
      formation of endothelial cells. Endothelial progenitor cells are known as a
      subset of circulating bone marrow mononuclear cells that have the capacity to
      differentiate into endothelial cells. However, the mechanism underlying the
      stimulatory effects of PGE2 and its specific receptors on bone marrow-derived
      cells (BMCs) in angiogenesis has not been fully characterized. Treatment with
      PGE2 significantly increased the differentiation and migration of BMCs. Also, the
      markers of differentiation to endothelial cells, CD31 and von Willebrand factor,
      and the genes associated with migration, matrix metalloproteinases 2 and 9, were
      significantly upregulated. This upregulation was abolished by dominant-negative
      AMP-activated protein kinase (AMPK) and AMPK inhibitor but not protein kinase, a
      inhibitor. As a functional consequence of differentiation and migration, the tube
      formation of BMCs was reinforced. Along with altered BMCs functions,
      phosphorylation and activation of AMPK and endothelial nitric oxide synthase, the
      target of activated AMPK, were both increased which could be blocked by EP4
      blocking peptide and simulated by the agonist of EP4 but not EP1, EP2 or EP3. The
      pro-angiogenic role of PGE2 could be repressed by EP4 blocking peptide and
      retarded in EP4(+/-) mice. Therefore, by promoting the differentiation and
      migration of BMCs, PGE2 reinforced their neovascularization by binding to the
      receptor of EP4 in an AMPK-dependent manner. PGE2 may have clinical value in
      ischemic heart disease.

PMID- 21876757
TI  - FGF-2 deficiency does not influence FGF ligand and receptor expression during
      development of the nigrostriatal system.
AB  - Secreted proteins of the fibroblast growth factor (FGF) family play important
      roles during development of various organ systems. A detailed knowledge of their
      temporal and spatial expression profiles, especially of closely related FGF
      family members, are essential to further identification of specific functions in
      distinct tissues. In the central nervous system dopaminergic neurons of the
      substantia nigra and their axonal projections into the striatum progressively
      degenerate in Parkinson's disease. In contrast, FGF-2 deficient mice display
      increased numbers of dopaminergic neurons. In this study, we determined the
      expression profiles of all 22 FGF-ligands and 10 FGF-receptor isoforms, in order
      to clarify, if FGF-2 deficiency leads to compensatory up-regulation of other FGFs
      in the nigrostriatal system. Three tissues, ventral mesencephalon (VM), striatum
      (STR) and as reference tissue spinal cord (SC) of wild-type and FGF-2 deficient
      mice at four developmental stages E14.5, P0, P28, and adult were comparatively
      analyzed by quantitative RT-PCR. As no differences between the genotypes were
      observed, a compensatory up-regulation can be excluded. Moreover, this analysis
      revealed that the majority of FGF-ligands (18/22) and FGF-receptors (9/10) are
      expressed during normal development of the nigrostriatal system and identified
      dynamic changes for some family members. By comparing relative expression level
      changes to SC reference tissue, general alterations in all 3 tissues, such as
      increased expression of FGF-1, -2, -22, FgfR-2c, -3c and decreased expression of
      FGF-13 during postnatal development were identified. Further, specific changes
      affecting only one tissue, such as increased FGF-16 (STR) or decreased FGF-17
      (VM) expression, or two tissues, such as decreased expression of FGF-8 (VM, STR)
      and FGF-15 (SC, VM) were found. Moreover, 3 developmentally down-regulated FGFs
      (FGF-8b, FGF-15, FGF-17a) were functionally characterized by plasmid-based over
      expression in dissociated E11.5 VM cell cultures, however, such a continuous
      exposure had no influence on the yield of dopaminergic neurons in vitro.

PMID- 21876758
TI  - MALDI-TOF high mass calibration up to 200 kDa using human recombinant 16 kDa
      protein histidine phosphatase aggregates.
AB  - BACKGROUND: Protein histidine phosphatase (PHP) is an enzyme which removes
      phosphate groups from histidine residues. It was described for vertebrates in the
      year 2002. The recombinant human 16 kDa protein forms multimeric complexes in
      physiological buffer and in the gas phase. High-mass calibration in matrix
      assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF
      MS) has remained a problem due to the lack of suitable standards. Large proteins
      can hardly be freed of their substructural microheterogeneity by classical
      purification procedures so that their use as calibrants is limited. A small
      adduct-forming protein of validated quality is a valuable alternative for that
      purpose. METHODOLOGY/PRINCIPAL FINDINGS: Three major PHP clusters of ~113, 209
      and >600 kDa were observed in gel filtration analysis. Re-chromatography of the
      monomer peak showed the same cluster distribution. The tendency to associate was
      detected also in MALDI-TOF MS measuring regular adducts up to 200 kDa.
      CONCLUSIONS/SIGNIFICANCE: PHP forms multimers consisting of up to more than 35
      protein molecules. In MALDI-TOF MS it generates adduct ions every 16 kDa. The
      protein can be produced with high quality so that its use as calibration compound
      for high mass ranges above 100 kDa, where standards are difficult to obtain, is
      feasible.

PMID- 21876759
TI  - Silencing of the rotavirus NSP4 protein decreases the incidence of biliary
      atresia in murine model.
AB  - Biliary atresia is a common disease in neonates which causes obstructive jaundice
      and progressive hepatic fibrosis. Our previous studies indicate that rotavirus
      infection is an initiator in the pathogenesis of experimental biliary atresia
      (BA) through the induction of increased nuclear factor-kappaB and abnormal
      activation of the osteopontin inflammation pathway. In the setting of rotavirus
      infection, rotavirus nonstructural protein 4 (NSP4) serves as an important
      immunogen, viral protein 7 (VP7) is necessary in rotavirus maturity and viral
      protein 4 (VP4) is a virulence determiner. The purpose of the current study is to
      clarify the roles of NSP4, VP7 and VP4 in the pathogenesis of experimental BA.
      Primary cultured extrahepatic biliary epithelia were infected with Rotavirus
      (mmu18006). Small interfering RNA targeting NSP4, VP7 or VP4 was transfected
      before rotavirus infection both in vitro and in vivo. We analyzed the incidence
      of BA, morphological change, morphogenesis of viral particles and viral mRNA and
      protein expression. The in vitro experiments showed NSP4 silencing decreased the
      levels of VP7 and VP4, reduced viral particles and decreased cytopathic effect.
      NSP4-positive cells had strongly positive expression of integrin subunit alpha2.
      Silencing of VP7 or VP4 partially decreased epithelial injury. Animal experiments
      indicated after NSP4 silencing, mouse pups had lower incidence of BA than after
      VP7 or VP4 silencing. However, 33.3% of VP4-silenced pups (N = 6) suffered BA and
      50% of pups (N = 6) suffered biliary injury after VP7 silencing. Hepatic injury
      was decreased after NSP4 or VP4 silencing. Neither VP4 nor VP7 were detected in
      the biliary ducts after NSP4. All together, NSP4 silencing down-regulates VP7 and
      VP4, resulting in decreased incidence of BA.

PMID- 21876760
TI  - Efficient and scalable purification of cardiomyocytes from human embryonic and
      induced pluripotent stem cells by VCAM1 surface expression.
AB  - RATIONALE: Human embryonic and induced pluripotent stem cells (hESCs/hiPSCs) are
      promising cell sources for cardiac regenerative medicine. To realize hESC/hiPSC
      based cardiac cell therapy, efficient induction, purification, and
      transplantation methods for cardiomyocytes are required. Though marker gene
      transduction or fluorescent-based purification methods have been reported, fast,
      efficient and scalable purification methods with no genetic modification are
      essential for clinical purpose but have not yet been established. In this study,
      we attempted to identify cell surface markers for cardiomyocytes derived from
      hESC/hiPSCs. METHOD AND RESULT: We adopted a previously reported differentiation
      protocol for hESCs based on high density monolayer culture to hiPSCs with some
      modification. Cardiac troponin-T (TNNT2)-positive cardiomyocytes appeared
      robustly with 30-70% efficiency. Using this differentiation method, we screened
      242 antibodies for human cell surface molecules to isolate cardiomyocytes derived
      from hiPSCs and identified anti-VCAM1 (Vascular cell adhesion molecule 1)
      antibody specifically marked cardiomyocytes. TNNT2-positive cells were detected
      at day 7-8 after induction and 80% of them became VCAM1-positive by day 11.
      Approximately 95-98% of VCAM1-positive cells at day 11 were positive for TNNT2.
      VCAM1 was exclusive with CD144 (endothelium), CD140b (pericytes) and TRA-1-60
      (undifferentiated hESCs/hiPSCs). 95% of MACS-purified cells were positive for
      TNNT2. MACS purification yielded 5-10*10(5) VCAM1-positive cells from a single
      well of a six-well culture plate. Purified VCAM1-positive cells displayed
      molecular and functional features of cardiomyocytes. VCAM1 also specifically
      marked cardiomyocytes derived from other hESC or hiPSC lines. CONCLUSION: We
      succeeded in efficiently inducing cardiomyocytes from hESCs/hiPSCs and
      identifying VCAM1 as a potent cell surface marker for robust, efficient and
      scalable purification of cardiomyocytes from hESC/hiPSCs. These findings would
      offer a valuable technological basis for hESC/hiPSC-based cell therapy.

PMID- 21876761
TI  - A signature in HIV-1 envelope leader peptide associated with transition from
      acute to chronic infection impacts envelope processing and infectivity.
AB  - Mucosal transmission of the human immunodeficiency virus (HIV) results in a
      bottleneck in viral genetic diversity. Gnanakaran and colleagues used a
      computational strategy to identify signature amino acids at particular positions
      in Envelope that were associated either with transmitted sequences sampled very
      early in infection, or sequences sampled during chronic infection. Among the
      strongest signatures observed was an enrichment for the stable presence of
      histidine at position 12 at transmission and in early infection, and a recurrent
      loss of histidine at position 12 in chronic infection. This amino acid lies
      within the leader peptide of Envelope, a region of the protein that has been
      shown to influence envelope glycoprotein expression and virion infectivity. We
      show a strong association between a positively charged amino acid like histidine
      at position 12 in transmitted/founder viruses with more efficient trafficking of
      the nascent envelope polypeptide to the endoplasmic reticulum and higher steady
      state glycoprotein expression compared to viruses that have a non-basic position
      12 residue, a substitution that was enriched among viruses sampled from
      chronically infected individuals. When expressed in the context of other viral
      proteins, transmitted envelopes with a basic amino acid position 12 were
      incorporated at higher density into the virus and exhibited higher infectious
      titers than did non-signature envelopes. These results support the potential
      utility of using a computational approach to examine large viral sequence data
      sets for functional signatures and indicate the importance of Envelope expression
      levels for efficient HIV transmission.

PMID- 21876762
TI  - TC-PTP dephosphorylates the guanine nucleotide exchange factor C3G (RapGEF1) and
      negatively regulates differentiation of human neuroblastoma cells.
AB  - The guanine nucleotide exchange factor, C3G (RapGEF1), functions in multiple
      signaling pathways involved in cell adhesion, proliferation, apoptosis and actin
      reorganization. C3G is regulated by tyrosine phosphorylation on Y504, known to be
      mediated by c-Abl and Src family kinases. In the present study we explored the
      possibility of cellular phospho-C3G (pC3G) being a substrate of the intracellular
      T-cell protein tyrosine phosphatase TC-PTP (PTPN2) using the human neuroblastoma
      cell line, IMR-32. In vivo and in vitro binding assays demonstrated interaction
      between C3G and TC-PTP. Interaction is mediated through the Crk-binding region of
      C3G and C-terminal noncatalytic residues of TC-PTP. C3G interacted better with a
      substrate trap mutant of TC48 and this complex formation was inhibited by
      vanadate. Endogenous pC3G colocalized with catalytically inactive mutant TC48 in
      the Golgi. Expression of TC48 abrogated pervanadate and c-Src induced
      phosphorylation of C3G without affecting total cellular phospho-tyrosine. Insulin
      like growth factor treatment of c-Src expressing cells resulted in
      dephosphorylation of C3G dependent on the activity of endogenous TC48. TC48
      expression inhibited forskolin induced tyrosine phosphorylation of C3G and
      neurite outgrowth in IMR-32 cells. Our results identify a novel Golgi localized
      substrate of TC48 and delineate a role for TC48 in dephosphorylation of
      substrates required during differentiation of human neuroblastoma cells.

PMID- 21876763
TI  - Nuclear importation of Mariner transposases among eukaryotes: motif requirements
      and homo-protein interactions.
AB  - Mariner-like elements (MLEs) are widespread transposable elements in animal
      genomes. They have been divided into at least five sub-families with differing
      host ranges. We investigated whether the ability of transposases encoded by Mos1,
      Himar1 and Mcmar1 to be actively imported into nuclei varies between host
      belonging to different eukaryotic taxa. Our findings demonstrate that nuclear
      importation could restrict the host range of some MLEs in certain eukaryotic
      lineages, depending on their expression level. We then focused on the nuclear
      localization signal (NLS) in these proteins, and showed that the first 175 N
      terminal residues in the three transposases were required for nuclear
      importation. We found that two components are involved in the nuclear importation
      of the Mos1 transposase: an SV40 NLS-like motif (position: aa 168 to 174), and a
      dimerization sub-domain located within the first 80 residues. Sequence analyses
      revealed that the dimerization moiety is conserved among MLE transposases, but
      the Himar1 and Mcmar1 transposases do not contain any conserved NLS motif. This
      suggests that other NLS-like motifs must intervene in these proteins. Finally, we
      showed that the over-expression of the Mos1 transposase prevents its nuclear
      importation in HeLa cells, due to the assembly of transposase aggregates in the
      cytoplasm.

PMID- 21876764
TI  - Biosynthetic gene cluster for the cladoniamides, bis-indoles with a rearranged
      scaffold.
AB  - The cladoniamides are bis-indole alkaloids isolated from Streptomyces uncialis, a
      lichen-associated actinomycete strain. The cladoniamides have an unusual,
      indenotryptoline structure rarely observed among bis-indole alkaloids. I report
      here the isolation, sequencing, and annotation of the cladoniamide biosynthetic
      gene cluster and compare it to the recently published gene cluster for BE-54017,
      a closely related indenotryptoline natural product. The cladoniamide gene cluster
      differs from the BE-54017 gene cluster in gene organization and in the absence of
      one N-methyltransferase gene but otherwise contains close homologs to all genes
      in the BE-54017 cluster. Both gene clusters encode enzymes needed for the
      construction of an indolocarbazole core, as well as flavin-dependent enzymes
      putatively involved in generating the indenotryptoline scaffold from an
      indolocarbazole. These two bis-indolic gene clusters exemplify the diversity of
      biosynthetic routes that begin from the oxidative dimerization of two molecules
      of L-tryptophan, highlight enzymes for further study, and provide new
      opportunities for combinatorial engineering.

PMID- 21876765
TI  - Development of an all-in-one lentiviral vector system based on the original TetR
      for the easy generation of Tet-ON cell lines.
AB  - Lentiviral vectors (LVs) are considered one of the most promising vehicles to
      efficiently deliver genetic information for basic research and gene therapy
      approaches. Combining LVs with drug-inducible expression systems should allow
      tight control of transgene expression with minimal side effect on relevant target
      cells. A new doxycycline-regulated system based on the original TetR repressor
      was developed in 1998 as an alternative to the TetR-VP16 chimeras (tTA and rtTA)
      to avoid secondary effects due to the expression of transactivator domains.
      However, previously described TetR-based systems required cell cloning and/or
      antibiotic selection of tetracycline-responsive cells in order to achieve good
      regulation. In the present manuscript we have constructed a dual Tet-ON system
      based on two lentiviral vectors, one expressing the TetR through the spleen focus
      forming virus (SFFV) promoter (STetR) and a second expressing eGFP through the
      regulatable CMV-TetO promoter (CTetOE). Using these vectors we have demonstrated
      that the TetR repressor, contrary to the reverse transactivator (rtTA), can be
      expressed in excess to bind and modulate a high number of TetO operons. We have
      also showed that this dual vector system can generate regulatable bulk cell lines
      (expressing high levels of TetR) that are able to modulate transgene expression
      either by varying doxycycline concentration and/or by varying the amount of
      CTetOE vector genomes per cell. Based on these results we have developed a new
      all-in-one lentiviral vector (CEST) driving the expression of TetR through the
      SFFV promoter and the expression of eGFP through the doxycycline-responsive CMV
      TetO operon. This vector efficiently produced Tet-ON regulatable immortalized
      (293T) and primary (human mesenchymal stem cells and human primary fibroblasts)
      cells. Bulk doxycycline-responsive cell lines express high levels of the
      transgene with low amount of doxycycline and are phenotypically indistinct from
      its parental cells.

PMID- 21876766
TI  - Hyperthermia induces the ER stress pathway.
AB  - BACKGROUND: The ER chaperone GRP78/BiP is a homolog of the Hsp70 family of heat
      shock proteins, yet GRP78/BiP is not induced by heat shock but instead by ER
      stress. However, previous studies had not considered more physiologically
      relevant temperature elevation associated with febrile hyperthermia. In this
      report we examine the response of GRP78/BiP and other components of the ER stress
      pathway in cells exposed to 40 degrees C. METHODOLOGY: AD293 cells were exposed
      to 43 degrees C heat shock to confirm inhibition of the ER stress response genes.
      Five mammalian cell types, including AD293 cells, were then exposed to 40 degrees
      C hyperthermia for various time periods and induction of the ER stress pathway
      was assessed. PRINCIPAL FINDINGS: The inhibition of the ER stress pathway by heat
      shock (43 degrees C) was confirmed. In contrast cells subjected to more mild
      temperature elevation (40 degrees C) showed either a partial or full ER stress
      pathway induction as determined by downstream targets of the three arms of the ER
      stress pathway as well as a heat shock response. Cells deficient for Perk or Gcn2
      exhibit great sensitivity to ER stress induction by hyperthermia. CONCLUSIONS:
      The ER stress pathway is induced partially or fully as a consequence of
      hyperthermia in parallel with induction of Hsp70. These findings suggest that the
      ER and cytoplasm of cells contain parallel pathways to coordinately regulate
      adaptation to febrile hyperthermia associated with disease or infection.

PMID- 21876767
TI  - MAGE I transcription factors regulate KAP1 and KRAB domain zinc finger
      transcription factor mediated gene repression.
AB  - Class I MAGE proteins (MAGE I) are normally expressed only in developing germ
      cells but are aberrantly expressed in many cancers. They have been shown to
      promote tumor survival, aggressive growth, and chemoresistance but the underlying
      mechanisms and MAGE I functions have not been fully elucidated. KRAB domain zinc
      finger transcription factors (KZNFs) are the largest group of vertebrate
      transcription factors and regulate neoplastic transformation, tumor suppression,
      cellular proliferation, and apoptosis. KZNFs bind the KAP1 protein and direct
      KAP1 to specific DNA sequences where it suppresses gene expression by inducing
      localized heterochromatin characterized by histone 3 lysine 9 trimethylation
      (H3me3K9). Discovery that MAGE I proteins also bind to KAP1 prompted us to
      investigate whether MAGE I can affect KZNF and KAP1 mediated gene regulation. We
      found that expression of MAGE I proteins, MAGE-A3 or MAGE-C2, relieved repression
      of a reporter gene by ZNF382, a KZNF with tumor suppressor activity. ChIP of MAGE
      I (-) HEK293T cells showed KAP1 and H3me3K9 are normally bound to the ID1 gene, a
      target of ZNF382, but that binding is greatly reduced in the presence of MAGE I
      proteins. MAGE I expression relieved KAP1 mediated ID1 repression, causing
      increased expression of ID1 mRNA and ID1 chromatin relaxation characterized by
      loss of H3me3K9. MAGE I binding to KAP1 also induced ZNF382 poly-ubiquitination
      and degradation, consistent with loss of ZNF382 leading to decreased KAP1 binding
      to ID1. In contrast, MAGE I expression caused increased KAP1 binding to Ki67,
      another KAP1 target gene, with increased H3me3K9 and decreased Ki67 mRNA
      expression. Since KZNFs are required to direct KAP1 to specific genes, these
      results show that MAGE I proteins can differentially regulate members of the KZNF
      family and KAP1 mediated gene repression.

PMID- 21876768
TI  - Differential bone marrow homing capacity of VLA-4 and CD38 high expressing
      chronic lymphocytic leukemia cells.
AB  - BACKGROUND: VLA-4 and CD38 predict a poor clinical outcome in chronic lymphocytic
      leukemia (CLL). We used CLL samples with discordant VLA-4/CD38 risk to address
      their individual roles in human bone marrow infiltration (BM), CLL cell homing to
      murine BM, and in supportive CLL cell-stromal cell interactions. METHODS: VLA-4,
      CD38, and Ki-67 expression was measured in CLL cells from peripheral blood (PB)
      and bone marrow (BM) aspirates. CLL BM infiltration rates, routinely determined
      by Pathology, were correlated to VLA-4 and CD38 expression. Short-term homing
      capacity of CLL cells was evaluated by adoptive transfer experiments. CLL cell
      viability and adhesion in stromal cell co-culture was determined. RESULTS: About
      20% of CLL samples in our cohort displayed discordant VLA-4 and CD38 risk, with
      either high VLA-4 and low CD38 risk or vice versa. Using particularly such
      samples, we observed that VLA-4, and not CD38, was responsible for recirculation
      of CLL cells to murine BM. Human BM infiltration was also significantly higher in
      patients with high VLA-4 risk but not high CD38 risk. However, both molecules
      acted as independent prognostic markers. While both VLA-4 and CD38 expression
      were increased in BM-derived CLL cells, and VLA-4+ and CD38+ subpopulations
      showed enriched Ki-67 expression, VLA-4 did not contribute to CLL cell protection
      by stromal cells in vitro. CONCLUSIONS: Our data argue for a prominent role of
      VLA-4 but not CD38 expression in the homing of CLL cells to BM niches and in
      human BM infiltration, but only a limited role in their protection by stromal
      cells.

PMID- 21876769
TI  - Reassessment of the lineage fusion hypothesis for the origin of double membrane
      bacteria.
AB  - In 2009, James Lake introduced a new hypothesis in which reticulate phylogeny
      reconstruction is used to elucidate the origin of gram-negative bacteria (Nature
      460: 967-971). The presented data supported the gram-negative bacteria
      originating from an ancient endosymbiosis between the Actinobacteria and
      Clostridia. His conclusion was based on a presence-absence analysis of protein
      families that divided all prokaryotes into five groups: Actinobacteria, Double
      Membrane bacteria (DM), Clostridia, Archaea and Bacilli. Of these five groups,
      the DM are by far the largest and most diverse group compared to the other
      groupings. While the fusion hypothesis for the origin of double membrane bacteria
      is enticing, we show that the signal supporting an ancient symbiosis is lost when
      the DM group is broken down into smaller subgroups. We conclude that the signal
      detected in James Lake's analysis in part results from a systematic artifact due
      to group size and diversity combined with low levels of horizontal gene transfer.

PMID- 21876770
TI  - A meta-analysis of global urban land expansion.
AB  - The conversion of Earth's land surface to urban uses is one of the most
      irreversible human impacts on the global biosphere. It drives the loss of
      farmland, affects local climate, fragments habitats, and threatens biodiversity.
      Here we present a meta-analysis of 326 studies that have used remotely sensed
      images to map urban land conversion. We report a worldwide observed increase in
      urban land area of 58,000 km(2) from 1970 to 2000. India, China, and Africa have
      experienced the highest rates of urban land expansion, and the largest change in
      total urban extent has occurred in North America. Across all regions and for all
      three decades, urban land expansion rates are higher than or equal to urban
      population growth rates, suggesting that urban growth is becoming more expansive
      than compact. Annual growth in GDP per capita drives approximately half of the
      observed urban land expansion in China but only moderately affects urban
      expansion in India and Africa, where urban land expansion is driven more by urban
      population growth. In high income countries, rates of urban land expansion are
      slower and increasingly related to GDP growth. However, in North America,
      population growth contributes more to urban expansion than it does in Europe.
      Much of the observed variation in urban expansion was not captured by either
      population, GDP, or other variables in the model. This suggests that contemporary
      urban expansion is related to a variety of factors difficult to observe
      comprehensively at the global level, including international capital flows, the
      informal economy, land use policy, and generalized transport costs. Using the
      results from the global model, we develop forecasts for new urban land cover
      using SRES Scenarios. Our results show that by 2030, global urban land cover will
      increase between 430,000 km(2) and 12,568,000 km(2), with an estimate of
      1,527,000 km(2) more likely.

PMID- 21876771
TI  - H5N1 whole-virus vaccine induces neutralizing antibodies in humans which are
      protective in a mouse passive transfer model.
AB  - BACKGROUND: Vero cell culture-derived whole-virus H5N1 vaccines have been
      extensively tested in clinical trials and consistently demonstrated to be safe
      and immunogenic; however, clinical efficacy is difficult to evaluate in the
      absence of wide-spread human disease. A lethal mouse model has been utilized
      which allows investigation of the protective efficacy of active vaccination or
      passive transfer of vaccine induced sera following lethal H5N1 challenge.
      METHODS: We used passive transfer of immune sera to investigate antibody-mediated
      protection elicited by a Vero cell-derived, non-adjuvanted inactivated whole
      virus H5N1 vaccine. Mice were injected intravenously with H5N1 vaccine-induced
      rodent or human immune sera and subsequently challenged with a lethal dose of
      wild-type H5N1 virus. RESULTS: Passive transfer of H5N1 vaccine-induced mouse,
      guinea pig and human immune sera provided dose-dependent protection of recipient
      mice against lethal challenge with wild-type H5N1 virus. Protective dose fifty
      values for serum H5N1 neutralizing antibody titers were calculated to be <=1?11
      for all immune sera, independently of source species. CONCLUSIONS: These data
      underpin the confidence that the Vero cell culture-derived, whole-virus H5N1
      vaccine will be effective in a pandemic situation and support the use of
      neutralizing serum antibody titers as a correlate of protection for H5N1
      vaccines.

PMID- 21876772
TI  - Olfactory cues from plants infected by powdery mildew guide foraging by a
      mycophagous ladybird beetle.
AB  - Powdery mildews (Erysiphales) are economically important plant pathogens that
      attack many agricultural crops. Conventional management strategies involving
      fungicide application face challenges, including the evolution of resistance and
      concerns over impacts on non-target organisms, that call for investigation of
      more sustainable alternatives. Mycophagous ladybird beetles (Coleoptera:
      Coccinellidae) feed on powdery mildew and have considerable potential as
      biological control agents; however, the foraging ecology and behavior of these
      beetles is not well understood. Here we document the olfactory cues presented by
      squash plants (Cucurbita moschata) infected by powdery mildew (Podosphaera sp.)
      and the behavioral responses of twenty-spotted ladybird beetles (Psyllobora
      vigintimaculata) to these cues. Volatile analyses through gas chromatography
      revealed a number of volatile compounds characteristic of infected plants,
      including 3-octanol and its analogues 1-octen-3-ol and 3-octanone. These
      compounds are typical "moldy" odorants previously reported in volatiles collected
      from other fungi. In addition, infected plants exhibited elevated emissions of
      several compounds also observed in collections from healthy leaves, including
      linalool and benzyl alcohol, which are reported to have anti-fungal properties.
      In Y-tube choice assays, P. vigintimaculata beetles displayed a significant
      preference for the odors of infected plants compared to those of healthy plants.
      Moreover, beetles exhibited strong attraction to one individual compound, 1-octen
      3-ol, which was the most abundant of the characteristic fungal compounds
      identified. These results enhance our understanding of the olfactory cues that
      guide foraging by mycophagous insects and may facilitate the development of
      integrated disease-management strategies informed by an understanding of
      underlying ecological mechanisms.

PMID- 21876775
TI  - Metabolic clues: novel directives for broad treatment strategies.

PMID- 21876774
TI  - Association analysis of canonical Wnt signalling genes in diabetic nephropathy.
AB  - AIMS/HYPOTHESIS: Several studies have provided compelling evidence implicating
      the Wnt signalling pathway in the pathogenesis of diabetic nephropathy. Gene
      expression profiles associated with renal fibrosis have been attenuated through
      Wnt pathway modulation in model systems implicating Wnt pathway members as
      potential therapeutic targets for the treatment of diabetic nephropathy. We
      assessed tag and potentially functional single nucleotide polymorphisms (SNPs; n
      = 31) in four key Wnt pathway genes (CTNNB1, AXIN2, LRP5 and LRP6) for
      association with diabetic nephropathy using a case-control design. METHODS: SNPs
      were genotyped using Sequenom or Taqman technologies in 1351 individuals with
      type 1 diabetes (651 cases with nephropathy and 700 controls without
      nephropathy). Cases and controls were white and recruited from the UK and
      Ireland. Association analyses were performed using PLINK, to compare allele and
      haplotype frequencies in cases and controls. Adjustment for multiple testing was
      performed by permutation testing. RESULTS: Following logistic regression analysis
      adjusted by collection centre, duration of T1D, and average HbA1c as covariates,
      a single SNP in LRP6 (rs1337791) was significantly associated with DN (OR = 0.74;
      CI: 0.57-0.97; P = 0.028), although this was not maintained following correction
      for multiple testing. Three additional SNPs (rs2075241 in LRP6; rs3736228 and
      rs491347 both in LRP5) were marginally associated with diabetic nephropathy, but
      none of the associations were replicated in an independent dataset. Haplotype and
      subgroup analysis (according to duration of diabetes, and end-stage renal
      disease) also failed to reveal an association with diabetic nephropathy.
      CONCLUSIONS/INTERPRETATION: Our results suggest that analysed common variants in
      CTNNB1, AXIN2, LRP5 and LRP6 are not strongly associated with diabetic
      nephropathy in type 1 diabetes among white individuals. Our findings, however,
      cannot entirely exclude these genes or other members of the Wnt pathway, from
      involvement in the pathogenesis of diabetic nephropathy as our study had limited
      power to detect variants with small effect size.

PMID- 21876773
TI  - IQGAP1 is a novel CXCR2-interacting protein and essential component of the
      "chemosynapse".
AB  - BACKGROUND: Chemotaxis is essential for a number of physiological processes
      including leukocyte recruitment. Chemokines initiate intracellular signaling
      pathways necessary for chemotaxis through binding seven transmembrane G protein
      couple receptors. Little is known about the proteins that interact with the
      intracellular domains of chemokine receptors to initiate cellular signaling upon
      ligand binding. CXCR2 is a major chemokine receptor expressed on several cell
      types, including endothelial cells and neutrophils. We hypothesize that multiple
      proteins interact with the intracellular domains of CXCR2 upon ligand stimulation
      and these interactions comprise a "chemosynapse", and play important roles in
      transducing CXCR2 mediated signaling processes. METHODOLOGY/PRINCIPAL FINDINGS:
      In an effort to define the complex of proteins that assemble upon CXCR2
      activation to relay signals from activated chemokine receptors, a proteomics
      approach was employed to identify proteins that co-associate with CXCR2 with or
      without ligand stimulation. The components of the CXCR2 "chemosynapse" are
      involved in processes ranging from intracellular trafficking to cytoskeletal
      modification. IQ motif containing GTPase activating protein 1 (IQGAP1) was among
      the novel proteins identified to interact directly with CXCR2. Herein, we
      demonstrate that CXCR2 co-localizes with IQGAP1 at the leading edge of polarized
      human neutrophils and CXCR2 expressing differentiated HL-60 cells. Moreover,
      amino acids 1-160 of IQGAP1 directly interact with the carboxyl-terminal domain
      of CXCR2 and stimulation with CXCL8 enhances IQGAP1 association with Cdc42.
      CONCLUSIONS: Our studies indicate that IQGAP1 is a novel essential component of
      the CXCR2 "chemosynapse".

PMID- 21876776
TI  - Hypertension in the elderly: Are we all on the same wavelength?
AB  - Hypertension is of frequent occurrence in the elderly population. Isolated
      systolic hypertension (ISH) accounts for the majority of cases of hypertension in
      the elderly. ISH is associated with a 2-4-fold increase in the risk of myocardial
      infarction, left ventricular hypertrophy, renal dysfunction, stroke, and
      cardiovascular mortality. There have been many studies to determine the optimal
      treatment for hypertension in the elderly. Why, when and how to treat
      hypertension in the elderly was the scope of the majority of these trials.
      Despite countless efforts many aspects remain obscure. While a number of novel
      drugs are being developed, the issue of whether all antihypertensive drugs bestow
      parallel benefits or whether some agents offer a therapeutic advantage beyond
      blood pressure control remains of crucial importance. Furthermore, the response
      of the elderly to different antihypertensive agents also differs from that of
      younger patients and may explain some of the disparities in outcomes of trials
      conducted in elderly patients with hypertension.

PMID- 21876778
TI  - Coronary spasm-related acute myocardial infarction in a patient with essential
      thrombocythemia.
AB  - We report a case of essential thrombocythemia (ET) in a 30-year-old female who
      exhibited inferior wall ST-elevation acute myocardial infarction (AMI) without
      significant obstructive coronary artery disease. Right coronary vasospasm was
      observed after intra-coronary methylergonovine administration and she received
      verapamil 120 mg/dthereafter and hydroxyurea 1500 mg/d for thrombocythemia. After
      discontinuation of the hydroxyurea for 9 mo based on the impression of coronary
      spasm-related instead of coronary thrombosis-related AMI, her platelet count rose
      but no chest pain was observed. It is suggested that coronary spasm potentially
      plays a role in patients with ET, AMI and no significant coronary artery
      stenosis.

PMID- 21876777
TI  - Current characteristics of congenital coronary artery fistulas in adults: A
      decade of global experience.
AB  - AIM: To describe the characteristics of coronary artery fistulas (CAFs) in
      adults, including donor vessels and whether termination was cameral or vascular.
      METHODS: A PubMed search was performed for articles between 2000 and 2010 to
      describe the current characteristics of congenital CAFs in adults. A group of 304
      adults was collected. Clinical data, presentations, diagnostic modalities,
      angiographic fistula findings and treatment strategies were gathered and
      analyzed. With regard to CAF origin, the subjects were tabulated into unilateral,
      bilateral or multilateral fistulas and compared. The group was stratified into
      two major subsets according to the mode of termination; coronary-cameral fistulas
      (CCFs) and coronary-vascular fistulas (CVFs). A comparison was made between the
      two subsets. Fistula-related major complications [aneurysm formation, infective
      endocarditis (IE), myocardial infarction (MI), rupture, pericardial effusion (PE)
      and tamponade] were described. Coronary artery-ventricular multiple micro
      fistulas and acquired CAFs were excluded as well as anomalous origin of the
      coronary arteries from the pulmonary artery (PA). RESULTS: A total of 304 adult
      subjects (47% male) with congenital CAFs were included. The mean age was 51.4
      years (range, 18-86 years), with 20% older than 65 years of age. Dyspnea (31%),
      chest pain (23%) and angina pectoris (21%) were the prevalent clinical
      presentations. Continuous cardiac murmur was heard in 82% of the subjects. Of the
      applied diagnostic modalities, chest X-ray showed an abnormal shadow in 4% of the
      subjects. The cornerstone in establishing the diagnosis was echocardiography
      (68%), and conventional contrast coronary angiography (97%). However, multi-slice
      detector computed tomography was performed in 16%. The unilateral fistula
      originated from the left in 69% and from the right coronary artery in 31% of the
      subjects. Most patients (80%) had unilateral fistulas, 18% presented with
      bilateral fistulas and 2% with multilateral fistulas. Termination into the PA was
      reported in unilateral (44%), bilateral (73%) and multilateral (75%) fistulas.
      Fistulas with multiple origins (bilateral and multilateral) terminated more
      frequently into the PA (29%) than into other sites (10.6%) (P = 0.000).
      Aneurysmal formation was found in 14% of all subjects. Spontaneous rupture, PE
      and tamponade were reported in 2% of all subjects. In CCFs, the mean age was 46.2
      years whereas in CVFs mean age was 55.6 years (P = 0.003). IE (4%) was
      exclusively associated with CCFs, while MI (2%) was only found in subjects with
      CVFs. Surgical ligation was frequently chosen for unilateral (57%), bilateral
      (51%) and multilateral fistulas (66%), but percutaneous therapeutic embolization
      (PTE) was increasingly reported (23%, 17% and 17%, respectively). CONCLUSION:
      Congenital CAFs are currently detected in elderly patients. Bilateral fistulas
      are more frequently reported and PTE is more frequently applied as a therapeutic
      strategy in adults.

PMID- 21876779
TI  - Human liver cells expressing albumin and mesenchymal characteristics give rise to
      insulin-producing cells.
AB  - Activation of the pancreatic lineage in the liver has been suggested as a
      potential autologous cell replacement therapy for diabetic patients.
      Transcription factors-induced liver-to-pancreas reprogramming has been
      demonstrated in numerous species both in vivo and in vitro. However, human
      derived liver cells capable of acquiring the alternate pancreatic repertoire have
      never been characterized. It is yet unknown whether hepatic-like stem cells or
      rather adult liver cells give rise to insulin-producing cells. Using an in vitro
      experimental system, we demonstrate that proliferating adherent human liver cells
      acquire mesenchymal-like characteristics and a considerable level of cellular
      plasticity. However, using a lineage-tracing approach, we demonstrate that
      insulin-producing cells are primarily generated in cells enriched for adult
      hepatic markers that coexpress both albumin and mesenchymal markers. Taken
      together, our data suggest that adult human hepatic tissue retains a substantial
      level of developmental plasticity, which could be exploited in regenerative
      medicine approaches.

PMID- 21876780
TI  - How to recondition ex vivo initially rejected donor lungs for clinical
      transplantation: clinical experience from lund university hospital.
AB  - A major problem in clinical lung transplantation is the shortage of donor lungs.
      Only about 20% of donor lungs are accepted for transplantation. We have recently
      reported the results of the first six double lung transplantations performed with
      donor lungs reconditioned ex vivo that had been deemed unsuitable for
      transplantation by the Scandiatransplant, Eurotransplant, and UK Transplant
      organizations because the arterial oxygen pressure was less than 40 kPa. The
      three-month survival of patients undergoing transplant with these lungs was 100%.
      One patient died due to sepsis after 95 days, and one due to rejection after 9
      months. Four recipients are still alive and well 24 months after transplantation,
      with no signs of bronchiolitis obliterans syndrome. The donor lungs were
      reconditioned ex vivo in an extracorporeal membrane oxygenation circuit using
      STEEN solution mixed with erythrocytes, to dehydrate edematous lung tissue.
      Functional evaluation was performed with deoxygenated perfusate at different
      inspired fractions of oxygen. The arterial oxygen pressure was significantly
      improved in this model. This ex vivo evaluation model is thus a valuable addition
      to the armamentarium in increasing the number of acceptable lungs in a donor
      population with inferior arterial oxygen pressure values, thereby, increasing the
      lung donor pool for transplantation. In the following paper we present our
      clinical experience from the first six patients in the world. We also present the
      technique we used in detail with flowchart.

PMID- 21876781
TI  - Transplantation tolerance induced in humans at the fetal or the neonatal stage.
AB  - Patients transplanted with HLA-mismatched stem cells from fetal livers develop
      transplantation tolerance to donor antigens. Engraftment needs no conditioning
      regimen prior to transplantation in neonates with severe combined
      immunodeficiency disease or in human fetal patients having not yet developed any
      immune maturity, especially T-cell differentiation. The chimeric patients have
      donor-derived T lymphocytes which progressively demonstrate positive interactions
      with other host cells. They also can be shown to be tolerant toward both host and
      donor antigens. The latter tolerance relies upon clonal deletion from the T-cell
      repertoire, and it results from the contact between thymocytes of donor origin
      and dendritic cells or macrophages also deriving from donor stem cells. The
      former tolerance does not imply clonal deletion of T-cells with host reactivity.
      Numerous T-cells recognizing the allogeneic, host-type antigens are identified in
      these patients, but these cells are anergized, following interaction with
      epithelial cells of the host thymus. Induction of transplantation tolerance at
      the fetal stage requires minimal engraftment only; in the future it will be
      possible to further amplify the clinical benefit, using additional cell
      transplants after birth.

PMID- 21876782
TI  - Cross-sectional serological survey of human fascioliasis in haiti.
AB  - Fasciola hepatica, the aetiological agent of fascioliasis in the Caribbean
      region, occurs throughout the major islands of the Greater Antilles and in
      localised zones on two islands (Martinique and Saint Lucia) of the Lesser
      Antilles. However, apart from Puerto Rico, information regarding human
      fascioliasis in islands of the Caribbean is out of date or unavailable, or even
      nonexistent as in Haiti. The authors conducted a retrospective, cross-sectional
      serological survey in Port-au-Prince using a Western blotting test (LDBIO
      Diagnostics) on human fascioliasis in Haiti. A total of 216 serum samples
      obtained from apparently healthy adults were tested. The frequency of antibodies
      in serum samples of the study population was 6.5% (14/216). The immunodominant
      bands recognised in Western blots were 27-28 kDa (100%), 42 kDa (64%), 60 kDa,
      and 8-9 kDa (28%). This is the first survey to reveal a relatively low proportion
      of asymptomatic F. hepatica-infected humans in Haiti.

PMID- 21876784
TI  - Could mineralocorticoids play a role in the pathophysiology of open angle
      glaucoma?
AB  - Since the pathomechanisms of primary open angle glaucoma are still not defined,
      different aspects related to this topic have to be discussed and further
      investigated. Possible candidates are the mineralocorticoids, which are known to
      lower intraocular pressure. A data search and personal investigations assume a
      limited role of mineralocorticoids for the development of glaucoma. Specific
      experiments for a final conclusion are, however, not yet performed.

PMID- 21876783
TI  - Comparison of protective immune responses to apicomplexan parasites.
AB  - Members of the phylum Apicomplexa, which includes the species Plasmodium,
      Eimeria, Toxoplasma, and Babesia amongst others, are the most successful
      intracellular pathogens known to humankind. The widespread acquisition of
      antimicrobial resistance to most drugs used to date has sparked a great deal of
      research and commercial interest in the development of vaccines as alternative
      control strategies. A few antigens from the asexual and sexual stages of
      apicomplexan development have been identified and their genes characterised;
      however, the fine cellular and molecular details of the effector mechanisms
      crucial for parasite inhibition and stimulation of protective immunity are still
      not entirely understood. This paper provides an overview of what is currently
      known about the protective immune response against the various types of
      apicomplexan parasites and focuses mainly on the similarities of these pathogens
      and their host interaction. Finally, the evolutionary relationships of these
      parasites and their hosts, as well as the modulation of immune functions that are
      critical in determining the outcome of the infection by these pathogenic
      organisms, are discussed.

PMID- 21876786
TI  - Vascular damage in kidney disease: beyond hypertension.
AB  - Chronic kidney disease (CKD) is highly prevalent and a multiplier of
      cardiovascular disease (CVD) and cannot be completely explained by traditional
      Framinghan risk factors. Consequently, greater emphasis has been placed in
      nontraditional risk factors, such as inflammation, endothelial dysfunction,
      sympathetic overactivation, protein-energy wasting oxidative stress, vascular
      calcification, and volume overload. The accumulation of uremic toxins (and the
      involvement of genetic factors) is responsible for many of the clinical
      consequences of a condition known as uremia. In this brief paper, we discuss
      mechanisms involved in the vascular damage of CKD patients, aiming to point out
      that important factors beyond hypertension are largely responsible for
      endothelial activation and increased CVD risk, with potential impact on risk
      stratification and development of novel therapeutic options.

PMID- 21876785
TI  - Molecular beacons: powerful tools for imaging RNA in living cells.
AB  - Recent advances in RNA functional studies highlights the pivotal role of these
      molecules in cell physiology. Diverse methods have been implemented to measure
      the expression levels of various RNA species, using either purified RNA or fixed
      cells. Despite the fact that fixed cells offer the possibility to observe the
      spatial distribution of RNA, assays with capability to real-time monitoring RNA
      transport into living cells are needed to further understand the role of RNA
      dynamics in cellular functions. Molecular beacons (MBs) are stem-loop hairpin
      structured oligonucleotides equipped with a fluorescence quencher at one end and
      a fluorescent dye (also called reporter or fluorophore) at the opposite end. This
      structure permits that MB in the absence of their target complementary sequence
      do not fluoresce. Upon binding to targets, MBs emit fluorescence, due to the
      spatial separation of the quencher and the reporter. Molecular beacons are
      promising probes for the development of RNA imaging techniques; nevertheless much
      work remains to be done in order to obtain a robust technology for imaging
      various RNA molecules together in real time and in living cells. The present work
      concentrates on the different requirements needed to use successfully MB for
      cellular studies, summarizing recent advances in this area.

PMID- 21876787
TI  - The age-dependent contribution of aortic incident and reflected pressure waves to
      central blood pressure in african-americans.
AB  - Aging is associated with increased central aortic systolic pressure (CSP) and
      pulse pressure which are predictive of cardiovascular events. Mechanisms
      implicated for higher central pressures include a higher forward incident
      pressure wave (P1), higher augmented pressure (AP), and shorter reflected wave
      round trip travel time (Tr). African-Americans (AA) have more frequent and
      deleterious blood pressure elevation. Using applanation tonometry, we studied the
      association of age and CSP with P1 and AP in 900 AA subjects. Data showed that in
      subjects <=50 years old, CSP was mediated by AP but not P1 or Tr, whereas in
      those >50, CSP was mediated by both AP and P1 and to a lesser extent by Tr.
      Predictive models were significant (R(2) = 0.97) for both age groups. In
      conclusion, wave reflection is the primary determinant of CSP in younger AA,
      while in older subjects, CSP is mediated by both the magnitude and timing of wave
      reflection as well as aortic impedance.

PMID- 21876788
TI  - Medical and psychological risk factors for incident hypertension in type 1
      diabetic african-americans.
AB  - Objective. To determine risk factors for the development of hypertension among
      African-Americans living with type 1 diabetes. Methods. African-Americans with
      type 1 diabetes (n = 483) participated in a 6-year followup. At both baseline and
      followup blood pressure was measured twice in both sitting and standing positions
      using a standard protocol. Patients had a structured clinical interview, ocular
      examination, retinal photographs, and blood and urine assays and completed the
      Hostility and Direction of Hostility Questionnaire (HDHQ) and the Beck Depression
      Inventory (BDI). Results. Of the 280 diabetic patients with no hypertension at
      baseline, 82 (29.3%) subsequently developed hypertension over the 6-year
      followup. Baseline older age, longer duration of diabetes, family history of
      hypertension, greater mean arterial blood pressure, overt proteinuria, increasing
      retinopathy severity, peripheral neuropathy, smoking, and higher hostility scores
      were significantly associated with the development of hypertension. Multivariate
      analyses showed that higher hostility scores and overt proteinuria were
      significantly and independently associated with the development of hypertension
      in this population. Conclusions. The development of hypertension in African
      Americans living with type 1 diabetes appears to be multifactorial and includes
      both medical (overt proteinuria) as well as psychological (high hostility) risk
      factors.

PMID- 21876789
TI  - Hypertension in the elderly.
AB  - Background. The incidence of hypertension in the Western countries is
      continuously increasing in the elderly population and remains the leading cause
      of cardiovascular and morbidity. Methods. we analysed some significant clinical
      trials in order to present the relevant findings on those hypertensive
      population. Results. Several studies (SYST-EUR, HYVET, CONVINCE, VALUE, etc.)
      have demonstrated the benefits of treatment (nitrendipine, hydrochrotiazyde,
      perindopril, indapamide, verapamil, or valsartan) in aged hypertensive patients
      not only concerning blood pressure values but also the other important risk
      factors. Conclusion. Hypertension is the most prevalent cardiovascular disorder
      in the Western countries, and the relevance of receiving pharmacological
      treatment of hypertension in aged patients is crucial; in addition, the results
      suggest that combination therapy-nitrendipine plus enalapril-could have more
      benefits than those observed with the use of nitrendipine alone.

PMID- 21876790
TI  - Assessment of the Morphological, Biochemical, and Kinetic Properties for Candida
      rugosa Lipase Immobilized on Hydrous Niobium Oxide to Be Used in the Biodiesel
      Synthesis.
AB  - Lipase from Candida rugosa (CRL) was immobilized by covalent attachment on
      hydrous niobium oxide. The matrix could effectively be attached to the enzyme
      with high retention of activity and prevent its leakage. Following
      immobilization, CRL exhibited improved storage stability and performed better at
      higher incubation temperatures. In addition, the enzyme retained most of its
      catalytic efficiency after successive operational cycles. The immobilized
      derivative was also fully characterized with respect to its morphological
      properties: particle size, surface specific area, and pore size distribution.
      Structural integrity and conformational changes, such as surface cavities in the
      support, set by the lipase procedure, were observed by Scanning Electron
      Microscopy. Additionally, a comparative study between free and immobilized
      lipases was provided in terms of pH, temperature, and thermal stability. CRL
      derivative was evaluated for the synthesis of biodiesel employing babassu oil and
      short chain alcohols. The process was feasible only for oil and butanol reaction
      system.

PMID- 21876791
TI  - Fluorescence Polarization Binding Assay for Aspergillus fumigatus Virulence
      Factor UDP-Galactopyranose Mutase.
AB  - Aspergillus fumigatus is an opportunistic human pathogenic fungus responsible for
      deadly lung infections in immunocompromised individuals. Galactofuranose (Galf)
      residues are essential components of the cell wall and play an important role in
      A. fumigatus virulence. The flavoenzyme UDP-galactopyranose mutase (UGM)
      catalyzes the isomerization of UDP-galactopyranose to UDP-galactofuranose, the
      biosynthetic precursor of Galf. Thus, inhibitors of UGM that block the
      biosynthesis of Galf can lead to novel chemotherapeutics for treating A.
      fumigatus-related diseases. Here, we describe the synthesis of fluorescently
      labeled UDP analogs and the development of a fluorescence polarization (FP)
      binding assay for A. fumigatus UGM (AfUGM). High-affinity binding to AfUGM was
      only obtained with the chromophore TAMRA, linked to UDP by either 2 or 6 carbons
      with K(d) values of 2.6 +/- 0.2 MUM and 3.0 +/- 0.7 MUM, respectively. These
      values were ~6 times lower than when UDP was linked to fluorescein. The FP assay
      was validated against several known ligands and displayed an excellent Z' factor
      (0.79 +/- 0.02) and good tolerance to dimethyl sulfoxide.

PMID- 21876793
TI  - Debittering of Protein Hydrolysates by Lactobacillus LBL-4 Aminopeptidase.
AB  - Yoghurt strain Lactobacillus LBL-4 cultivated for 8-10 h at pH ~6.0 was
      investigated as a considerable food-grade source of intracellular aminopeptidase.
      Cell-free extract manifesting >200 AP U/l was obtained from cells harvested from
      1 L culture media. Subtilisin-induced hydrolysates of casein, soybean isolate,
      and Scenedesmus cell protein with degree of hydrolysis 20-22% incubated at 45
      degrees C for 10 h by 10 AP U/g peptides caused an enlarging of DH up to 40-42%,
      46-48%, and 38-40% respectively. The DH increased rapidly during the first 4 h,
      but gel chromatography studies on BioGel P-2 showed significant changes occurred
      during 4-10 h of enzyme action when the DH increased gradually. After the
      digestion, the remained AP activity can be recovered by ultrafiltration (yield 40
      50%). Scenedesmus protein hydrolysate with DH 20% was inoculated by Lactobacillus
      LBL-4 cells, and after 72 h cultivation the DH reached 32%. The protein
      hydrolysates (DH above 40%) obtained from casein and soybean isolate (high Q
      value) demonstrated a negligible bitterness while Scenedesmus protein
      hydrolysates (low Q value) after both treatments were free of bitterness.

PMID- 21876792
TI  - Protein kinase C and toll-like receptor signaling.
AB  - Protein kinase C (PKC) is a family of kinases that are implicated in a plethora
      of diseases, including cancer and cardiovascular disease. PKC isoforms can have
      different, and sometimes opposing, effects in these disease states. Toll-like
      receptors (TLRs) are a family of pattern recognition receptors that bind
      pathogens and stimulate the secretion of cytokines. It has long been known that
      PKC inhibitors reduce LPS-stimulated cytokine secretion by macrophages, linking
      PKC activation to TLR signaling. Recent studies have shown that PKC-alpha, 
      delta, -epsilon, and -zeta are directly involved in multiple steps in TLR
      pathways. They associate with the TLR or proximal components of the receptor
      complex. These isoforms are also involved in the downstream activation of MAPK,
      RhoA, TAK1, and NF-kappaB. Thus, PKC activation is intimately involved in TLR
      signaling and the innate immune response.

PMID- 21876794
TI  - An Examination by Site-Directed Mutagenesis of Putative Key Residues in the
      Determination of Coenzyme Specificity in Clostridial NAD-Dependent Glutamate
      Dehydrogenase.
AB  - Sequence and structure comparisons of various glutamate dehydrogenases (GDH) and
      other nicotinamide nucleotide-dependent dehydrogenases have potentially
      implicated certain residues in coenzyme binding and discrimination. We have
      mutated key residues in Clostridium symbiosum NAD(+)-specific GDH to investigate
      their contribution to specificity and to enhance acceptance of NADPH. Comparisons
      with E. coli NADPH-dependent GDH prompted design of mutants F238S, P262S, and
      F238S/P262S, which were purified and assessed at pH 6.0, 7.0, and 8.0. They
      showed markedly increased catalytic efficiency with NADPH, especially at pH 8.0
      (~170-fold for P262S and F238S/P262S with relatively small changes for NADH). A
      positive charge introduced through the D263K mutation also greatly increased
      catalytic efficiency with NADPH (over 100-fold at pH 8) and slightly decreased
      activity with NADH. At position 242, "P6" of the "core fingerprint," where NAD(+)
      and NADP(+)-dependent enzymes normally have Gly or Ala, respectively,
      clostridial GDH already has Ala. Replacement with Gly produced negligible shift
      in coenzyme specificity.

PMID- 21876795
TI  - Garlic and onion attenuates vascular inflammation and oxidative stress in
      fructose-fed rats.
AB  - This study evaluates the antioxidant and the anti-inflammatory properties of
      garlic (G) and onion (O) in fructose-fed rats (FFR). Thirty-day-old male Wistar
      rats were assigned to control (C), F (10% fructose in drinking water), F+T
      (tempol 1 mM as control antioxidant), F+G, and F+O. Aqueous G and O extracts were
      administered orally in doses of 150 and 400 mg/kg/d respectively, and along with
      tempol, were given during the last 8 weeks of a 14-week period. At the end of the
      study, FFR had developed insulin resistance, aortic NADPH oxidase activity,
      increased SBP, plasma TBARS and vascular cell adhesion molecule-1 (VCAM-1)
      expression in mesenteric arteries, and a decrease in heart endothelial nitric
      oxide synthase (eNOS). Garlic and onion administration to F rats reduced
      oxidative stress, increased eNOS activity, and also attenuated VCAM-1 expression.
      These results provide new evidence showing the anti-inflammatory and antioxidant
      effect of these vegetables.

PMID- 21876797
TI  - Multidisciplinary approach to child and adolescent depression.

PMID- 21876796
TI  - Personality Profiles Identify Depressive Symptoms over Ten Years? A Population
      Based Study.
AB  - Little is known about the relationship between temperament and character
      inventory (TCI) profiles and depressive symptoms. Personality profiles are
      useful, because personality traits may have different effects on depressive
      symptoms when combined with different combinations of other traits. Participants
      were from the population-based Young Finns study with repeated measurements in
      1997, 2001, and 2007 (n = 1402 to 1902). TCI was administered in 1997 and mild
      depressive symptoms (modified Beck's depression inventory, BDI) were reported in
      1997, 2001, and 2007. BDI-II was also administered in 2007. We found that high
      harm avoidance and low self-directedness related strongly to depressive symptoms.
      In addition, sensitive (NHR) and fanatical people (ScT) were especially
      vulnerable to depressive symptoms. high novelty seeking and reward dependence
      increased depressive symptoms when harm avoidance was high. These associations
      were very similar in cross-sectional and longitudinal analysis. Personality
      profiles help in understanding the complex associations between depressive
      symptoms and personality.

PMID- 21876798
TI  - Erratum to "factors influencing oxidative imbalance in pulmonary fibrosis: an
      immunohistochemical study".

PMID- 21876799
TI  - Perfluorochemical liquid-adenovirus suspensions enhance gene delivery to the
      distal lung.
AB  - WE COMPARED LUNG DELIVERY METHODS OF RECOMBINANT ADENOVIRUS (RAD): (1) rAd
      suspended in saline, (2) rAd suspended in saline followed by a pulse-chase of a
      perfluorochemical (PFC) liquid mixture, and (3) a PFC-rAd suspension. Cell
      uptake, distribution, and temporal expression of rAd were examined using A549
      cells, a murine model using luciferase bioluminescence, and histological
      analyses. Relative to saline, a 4X increase in transduction efficiency was
      observed in A549 cells exposed to PFC-rAd for 2-4 h. rAd transgene expression was
      improved in alveolar epithelial cells, and the level and distribution of
      luciferase expression when delivered in PFC-rAd suspensions consistently peaked
      at 24 h. These results demonstrate that PFC-rAd suspensions improve distribution
      and enhance rAd-mediated gene expression which has important implications in
      improving lung function by gene therapy.

PMID- 21876800
TI  - Huntington's Disease: An Immune Perspective.
AB  - Huntington's disease (HD) is a progressive neurodegenerative disorder that is
      caused by abnormal expansion of CAG trinucleotide repeats. Neuroinflammation is a
      typical feature of most neurodegenerative diseases that leads to an array of
      pathological changes within the affected areas in the brain. The
      neurodegeneration in HD is also caused by aberrant immune response in the
      presence of aggregated mutant huntingtin protein. The effects of immune
      activation in HD nervous system are a relatively unexplored area of research.
      This paper summarises immunological features associated with development and
      progression of HD.

PMID- 21876801
TI  - The hyponatremic hypertensive syndrome in a preterm infant: a case of severe
      hyponatremia with neurological sequels.
AB  - Objective. To report the irreversible severe neurological symptoms following the
      hyponatremic hypertensive syndrome (HHS) in an infant after umbilical arterial
      catheterization. Design. Case report with review of the literature. Setting.
      Neonatal intensive care unit at a tertiary care children's hospital. Patient. A
      three-week-old preterm infant. Conclusions. In evaluating a neonate with
      hyponatremia and hypertension, HHS should be considered, especially in case of
      umbilical arterial catheterization. In case of diagnostic delay, there is a risk
      of severe irreversible neurological damage.

PMID- 21876802
TI  - Pleuroperitoneal leak complicating peritoneal dialysis: a case series.
AB  - Pressure related complications such as abdominal wall hernias occur with relative
      frequency in patients on peritoneal dialysis. Less frequently, a transudative
      pleural effusion containing dialysate can develop. This phenomenon appears to be
      due to increased intra-abdominal pressure in the setting of congenital or
      acquired diaphragmatic defects. We report three cases of pleuroperitoneal leak
      that occurred within a nine-month period at our institution. We review the
      literature on this topic, and discuss management options. The pleural effusion
      resolved in one patient following drainage of the peritoneum and a switch to
      haemodialysis. One patient required emergency thoracocentesis. The third patient
      developed a complex effusion requiring surgical intervention. The three cases
      highlight the variability of this condition in terms of timing, symptoms and
      management. The diagnosis of a pleuroperitoneal leak is an important one as it is
      managed very differently to most transudative pleural effusions seen in this
      patient population. Surgical repair may be necessary in those patients who wish
      to resume peritoneal dialysis, or in those patients with complex effusions.
      Pleuroperitoneal leak should be considered in the differential diagnosis of a
      pleural effusion, particularly a right-sided effusion, in a patient on peritoneal
      dialysis.

PMID- 21876804
TI  - Stroke in the very old: a systematic review of studies on incidence, outcome, and
      resource use.
AB  - Background and Purpose. Stroke incidence increases with age and is likely to
      increase in the aging populations. We investigated incidence, outcome, and
      resource use in very old subjects with stroke. Methods. We performed a systematic
      review of available data through electronic search of the literature databases
      and manual search of reference lists. Data were extracted for the age groups of
      over 80, 80 to 84 years old, and over 85. Overall incidence rates, expressed as
      the number of first strokes per 1000 person-years, were estimated using Poisson
      regression analysis. Odds ratios for the comparisons between subjects over and
      under 80 were calculated with the Mantel-Haenszel method. Results. We found a
      high incidence of stroke in the very old. The estimated incidence rates were
      20.78 (95% CI 19.69 to 21.87) in subjects over 80, 17.23 (95% CI 15.97 to 18.49)
      for those 80 to 85 years old, and 20.78 (95% CI 16.74 to 23.78) for those over
      85. Subjects over 80 contributed 29.95% of strokes; rates were similar among
      genders. Thirty-day case fatality rate and occurrence of dependency were higher
      in subjects over 80, although associated with less frequent hospital and stroke
      unit admission and less diagnostic resource use. Conclusions. The contribution of
      very old subjects to the global burden of stroke is relevant and may require
      efficient dedicated stroke services.

PMID- 21876803
TI  - Hemolytic uremic syndrome: new developments in pathogenesis and treatment.
AB  - Hemolytic uremic syndrome is defined by the characteristic triad of
      microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. In
      children, most cases of HUS are caused by Shiga-toxin-producing bacteria,
      especially Escherichia coli O157:H7. Common vehicles of transmission include
      ground beef, unpasteurized milk, and municipal or swimming water. Shiga-toxin
      associated HUS is a main cause of acute renal failure in young children.
      Management remains supportive as there is at present no specific therapy to
      ameliorate the prognosis. Immediate outcome is most often favourable but long
      term renal sequelae are frequent due to nephron loss. Atypical HUS represents 5%
      of cases. In the past 15 years, mutations in complement regulators of the
      alternative pathway have been identified in almost 60% of cases, leading to
      excessive complement activation. The disease has a relapsing course and more than
      half of the patients either die or progress to end-stage renal failure.
      Recurrence after renal transplantation is frequent.

PMID- 21876805
TI  - Compression of morbidity 1980-2011: a focused review of paradigms and progress.
AB  - The Compression of Morbidity hypothesis-positing that the age of onset of chronic
      illness may be postponed more than the age at death and squeezing most of the
      morbidity in life into a shorter period with less lifetime disability-was
      introduced by our group in 1980. This paper is focused upon the evolution of the
      concept, the controversies and responses, the supportive multidisciplinary
      science, and the evolving lines of evidence that establish proof of concept. We
      summarize data from 20-year prospective longitudinal studies of lifestyle
      progression of disability, national population studies of trends in disability,
      and randomized controlled trials of risk factor reduction with life-style-based
      "healthy aging" interventions. From the perspective of this influential and
      broadly cited paradigm, we review its current history, the development of a
      theoretical structure for healthy aging, and the challenges to develop coherent
      health policies directed at reduction in morbidity.

PMID- 21876806
TI  - Lifespan and glucose metabolism in insulin receptor mutant mice.
AB  - Insulin/insulin-like growth factor type 1 signaling regulates lifespan and
      resistance to oxidative stress in worms, flies, and mammals. In a previous study,
      we revealed that insulin receptor (IR) mutant mice, which carry a homologous
      mutation found in the long-lived daf-2 mutant of Caenorhabditis elegans, showed
      enhanced resistance to oxidative stress cooperatively modulated by sex hormones
      and dietary signals (Baba et al., (2005)). We herein investigated the lifespan of
      IR mutant mice to evaluate the biological significance of insulin signaling in
      mice. Under normoxia, mutant male mice had a lifespan comparable to that of wild
      type male mice. IR mutant female mice also showed a lifespan similar to that of
      wild-type female mice, in spite of the fact that the IR mutant female mice
      acquired more resistance to oxidative stress than IR mutant male mice. On the
      other hand, IR mutant male and female mice both showed insulin resistance with
      hyperinsulinemia, but they did not develop hyperglycemia throughout their entire
      lifespan. These data indicate that the IR mutation does not impact the lifespan
      in mice, thus suggesting that insulin signaling might have a limited effect on
      the lifespan of mice.

PMID- 21876807
TI  - Mobility and aging: transference to transportation.

PMID- 21876808
TI  - Interactions of aging, overload, and creatine supplementation in rat plantaris
      muscle.
AB  - Attenuation of age-related sarcopenia by creatine supplementation has been
      equivocal. In this study, plantaris muscles of young (Y; 5m) and aging (A; 24m)
      Fisher 344 rats underwent four weeks of either control (C), creatine
      supplementation (Cr), surgical overload (O), or overload plus creatine (OCr).
      Creatine alone had no effect on muscle fiber cross-sectional area (CSA) or heat
      shock protein (HSP70) and increased myonuclear domain (MND) only in young rats.
      Overload increased CSA and HSP70 content in I and IIA fibers, regardless of age,
      and MND in IIA fibers of YO rats. CSA and MND increased in all fast fibers of
      YOCr, and CSA increased in I and IIA fibers of AOCr. OCR did not alter HSP70,
      regardless of age. MND did not change in aging rats, regardless of treatment.
      These data indicate creatine alone had no significant effect. Creatine with
      overload produced no additional hypertrophy relative to overload alone and
      attenuated overload-induced HSP70 expression.

PMID- 21876809
TI  - Neurobiology of vascular dementia.
AB  - Vascular dementia is, in its current conceptual form, a distinct type of dementia
      with a spectrum of specific clinical and pathophysiological features. However, in
      a very large majority of cases, these alterations occur in an already aged brain,
      characterized by a milieu of cellular and molecular events common for different
      neurodegenerative diseases. The cell signaling defects and molecular
      dyshomeostasis might lead to neuronal malfunction prior to the death of neurons
      and the alteration of neuronal networks. In the present paper, we explore some of
      the molecular mechanisms underlying brain malfunction triggered by
      cerebrovascular disease and risk factors. We suggest that, in the age of genetic
      investigation and molecular diagnosis, the concept of vascular dementia needs a
      new approach.

PMID- 21876811
TI  - Exploring Positive and Negative Affect as Key Indicators of Life Satisfaction
      among Centenarians: Does Cognitive Performance Matter?
AB  - The aim of this investigation was to determine how cognitive performance was
      associated with positive and negative affect and life satisfaction over time.
      This study involved a secondary longitudinal analysis of cross-section data
      collected at Phase I (1988-1992) and during an 18-month longitudinal followup at
      Phase II (1992-1998) of the Georgia Centenarian Study. Participants included N =
      137 centenarians at Time 1 and N = 68 survivors at Time 2. Significant stability
      in cognitive impairment existed at Time 1 and Time 2 for positive (beta = .55, P
      < .01) and negative affect (beta = .54, P < .01) models. Negative affect at Time
      1 was associated with lower life satisfaction at Time 1 (beta = -.42, P < .01 ).
      In addition, cognitive impairment at Time 2 was associated with decreased
      positive emotionality at Time 2 (beta = -.39, P > .01). Furthermore, greater
      positive affect at Time 2 was associated with greater satisfaction with life at
      Time 2 (beta = .35, P < .01). It appears that positive emotionality
      contemporaneously influences the association between cognitive impairment and
      life satisfaction among centenarians. Implications relative to improving life
      satisfaction among centenarians are discussed.

PMID- 21876810
TI  - Age-related white matter changes.
AB  - Age-related white matter changes (WMC) are considered manifestation of
      arteriolosclerotic small vessel disease and are related to age and vascular risk
      factors. Most recent studies have shown that WMC are associated with a host of
      poor outcomes, including cognitive impairment, dementia, urinary incontinence,
      gait disturbances, depression, and increased risk of stroke and death. Although
      the clinical relevance of WMC has been extensively studied, to date, only very
      few clinical trials have evaluated potential symptomatic or preventive treatments
      for WMC. In this paper, we reviewed the current understanding in the
      pathophysiology, epidemiology, clinical importance, chemical biomarkers, and
      treatments of age-related WMC.

PMID- 21876812
TI  - Cost effectiveness of a home-based intervention that helps functionally
      vulnerable older adults age in place at home.
AB  - Evaluating cost effectiveness of interventions for aging in place is essential
      for adoption in service settings. We present the cost effectiveness of Advancing
      Better Living for Elders (ABLE), previously shown in a randomized trial to reduce
      functional difficulties and mortality in 319 community-dwelling elders. ABLE
      involved occupational and physical therapy sessions and home modifications to
      address client-identified functional difficulties, performance goals, and home
      safety. Incremental cost-effectiveness ratio (ICER), expressed as additional cost
      to bring about one additional year of life, was calculated. Two models were then
      developed to account for potential cost differences in implementing ABLE.
      Probabilistic sensitivity analyses were conducted to account for variations in
      model parameters. By two years, there were 30 deaths (9: ABLE; 21: control).
      Additional costs for 1 additional year of life was $13,179 for Model 1 and
      $14,800 for Model 2. Investment in ABLE may be worthwhile depending on society's
      willingness to pay.

PMID- 21876813
TI  - Hypertriglyceridemia, Metabolic Syndrome, and Cardiovascular Disease in HIV
      Infected Patients: Effects of Antiretroviral Therapy and Adipose Tissue
      Distribution.
AB  - The use of combination antiretroviral therapy (CART) in HIV-infected patients has
      resulted in a dramatic decline in AIDS-related mortality. However, mortality due
      to non-AIDS conditions, particularly cardiovascular disease (CVD) seems to
      increase in this population. CART has been associated with several metabolic risk
      factors, including insulin resistance, low HDL-cholesterol, hypertriglyceridemia
      and postprandial hyperlipidemia. In addition, HIV itself, as well as specific
      antiretroviral agents, may further increase cardiovascular risk by interfering
      with endothelial function. As the HIV population is aging, CVD may become an
      increasingly growing health problem in the future. Therefore, early diagnosis and
      treatment of cardiovascular risk factors is warranted in this population. This
      paper reviews the contribution of both, HIV infection and CART, to insulin
      resistance, postprandial hyperlipidemia and cardiovascular risk in HIV-infected
      patients. Strategies to reduce cardiovascular risk are also discussed.

PMID- 21876814
TI  - Phospholipase A2 mediates apolipoprotein-independent uptake of chylomicron
      remnant-like particles by human macrophages.
AB  - Apolipoprotein E-receptor-mediated pathways are the main routes by which
      macrophages take up chylomicron remnants, but uptake may also be mediated by
      receptor-independent routes. To investigate these mechanisms, triacylglycerol
      (TG) accumulation induced by apolipoprotein-free chylomicron remnant-like
      particles (CRLPw/o) in human monocyte-derived macrophages was evaluated.
      Macrophage TG content increased about 5-fold after incubation with CRLPw/o, and
      this effect was not reduced by the inhibition of phagocytosis, macropinocytosis,
      apolipoprotein E function, or proteoglycan bridging. The role of lipases,
      including lipoprotein lipase, cholesteryl ester hydrolase, and secretory (sPLA2)
      and cytosolic phospholipase A2, was studied using [(3)H]TG-labelled CRLPw/o.
      Total cell radioactivity after incubation with [(3)H]TG CRLPw/o was reduced by 15
      30% by inhibitors of lipoprotein lipase and cholesteryl ester hydrolase and by
      about 45% by inhibitors of sPLA2 and cytosolic PLA(2) . These results suggest
      that macrophage lipolytic enzymes mediate the internalization of postprandial TG
      rich lipoproteins and that sPLA(2) and cytosolic PLA2, play a more important role
      than extracellular lipoprotein lipase-mediated TG hydrolysis.

PMID- 21876815
TI  - Cell Uptake and Validation of Novel PECs for Biomedical Applications.
AB  - This pilot study provides the proof of principle for biomedical application of
      novel polyelectrolyte complexes (PECs) obtained via electrostatic interactions
      between dextran sulphate (DXS) and poly(allylamine hydrochloride) (PAH). Scanning
      electron microscopy (SEM) and atomic force microscopy (AFM) showed that DXS/PAH
      polyelectrolyte complexes were Monodispersed with regular rounded-shape features
      and average diameters of 250 nm at 2 : 1 weight ratios of DXS/PAH. Fluorescently
      labelled DXS and fluorescein-isothiocyanate- (FITC-)conjugate DXS were used to
      follow cell uptake efficiency of PECs and biodegradability of their enzymatically
      degradable DXS-layers by using confocal laser scanning microscopy (CLSM).
      Moreover, quantitative MTT and Trypan Blue assays were employed to validate PECs
      as feasible and safe nanoscaled carriers at single-cell level without adverse
      effects on metabolism and viability.

PMID- 21876816
TI  - Recovery of Bacillus licheniformis Alkaline Protease from Supernatant of
      Fermented Wastewater Sludge Using Ultrafiltration and Its Characterization.
AB  - Investigation on recovery of alkaline protease from B. licheniformis ATCC 21424
      fermented wastewater sludge was carried out by centrifugation and
      ultrafiltration. Optimization of ultrafiltration parameters (transmembrane
      pressure (TMP) and feed flux) was carried out with 10 kDa membrane. TMP of 90 kPa
      and feed flux of 714 L/h/m(2) gave highest recovery (83%) of the enzyme from the
      centrifuged supernatant. The recovered enzyme had given maximum activity at
      temperature of 60 degrees C and at pH 10. It was stable between pH 8 to 10 and
      retained 97% activity at 60 degrees C after 180 min of incubation. Enzyme
      activity was significantly augmented by metal ions like Ca(2+) and Mn(2+).
      Protease inhibitors like phenylmethyl sulphonyl fluoride (PMSF) and diisopropyl
      fluorophosphates (DFPs) completely inhibited the enzyme activity. The partially
      purified protease showed excellent stability and compatibility with various
      commercial detergents. The detergent (Sunlight) removed the blood stains
      effectively along with the enzyme as additive.

PMID- 21876817
TI  - Whole slide quantification of stromal lymphatic vessel distribution and
      peritumoral lymphatic vessel density in early invasive cervical cancer: a method
      description.
AB  - Peritumoral Lymphatic Vessel Density (LVD) is considered to be a predictive
      marker for the presence of lymph node metastases in cervical cancer. However,
      when LVD quantification relies on conventional optical microscopy and the hot
      spot technique, interobserver variability is significant and yields inconsistent
      conclusions. In this work, we describe an original method that applies computed
      image analysis to whole slide scanned tissue sections following
      immunohistochemical lymphatic vessel staining. This procedure allows to determine
      an objective LVD quantification as well as the lymphatic vessel distribution and
      its heterogeneity within the stroma surrounding the invasive tumor bundles. The
      proposed technique can be useful to better characterize lymphatic vessel
      interactions with tumor cells and could potentially impact on prognosis and
      therapeutic decisions.

PMID- 21876818
TI  - Histaminergic mechanisms for modulation of memory systems.
AB  - Encoding for several memory types requires neural changes and the activity of
      distinct regions across the brain. These areas receive broad projections
      originating in nuclei located in the brainstem which are capable of modulating
      the activity of a particular area. The histaminergic system is one of the major
      modulatory systems, and it regulates basic homeostatic and higher functions
      including arousal, circadian, and feeding rhythms, and cognition. There is now
      evidence that histamine can modulate learning in different types of behavioral
      tasks, but the exact course of modulation and its mechanisms are controversial.
      In the present paper we review the involvement of the histaminergic system and
      the effects histaminergic receptor agonists/antagonists have on the performance
      of tasks associated with the main memory types as well as evidence provided by
      studies with knockout models. Thus, we aim to summarize the possible effects
      histamine has on modulation of circuits involved in memory formation.

PMID- 21876819
TI  - Mechanisms of GABAergic homeostatic plasticity.
AB  - Homeostatic plasticity ensures that appropriate levels of activity are maintained
      through compensatory adjustments in synaptic strength and cellular excitability.
      For instance, excitatory glutamatergic synapses are strengthened following
      activity blockade and weakened following increases in spiking activity. This form
      of plasticity has been described in a wide array of networks at several different
      stages of development, but most work and reviews have focussed on the excitatory
      inputs of excitatory neurons. Here we review homeostatic plasticity of GABAergic
      neurons and their synaptic connections. We propose a simplistic model for
      homeostatic plasticity of GABAergic components of the circuitry (GABAergic
      synapses onto excitatory neurons, excitatory connections onto GABAergic neurons,
      cellular excitability of GABAergic neurons): following chronic activity blockade
      there is a weakening of GABAergic inhibition, and following chronic increases in
      network activity there is a strengthening of GABAergic inhibition. Previous work
      on GABAergic homeostatic plasticity supports certain aspects of the model, but it
      is clear that the model cannot fully account for some results which do not appear
      to fit any simplistic rule. We consider potential reasons for these
      discrepancies.

PMID- 21876821
TI  - Swimming exercise in the acute or late phase after sciatic nerve crush
      accelerates nerve regeneration.
AB  - There is no consensus about the best time to start exercise after peripheral
      nerve injury. We evaluated the morphological and functional characteristics of
      the sciatic nerves of rats that began to swim immediately after crush nerve
      injury (CS1), those that began to swim 14 days after injury (CS14), injured rats
      not submitted to swimming (C), and uninjured rats submitted to swimming (S).
      After 30 days the number of axons in CS1 and CS14 was lower than in C (P < 0.01).
      The diameter of axons and nerve fibers was larger in CS1 (P < 0.01) and CS14 (P <
      0.05) than in C, and myelin sheath thickness was lower in all crushed groups (P <
      0.05). There was no functional difference between CS1 and CS14 (P > 0.05).
      Swimming exercise applied during the acute or late phase of nerve injury
      accelerated nerve regeneration and synaptic elimination after axonotmesis,
      suggesting that exercise may be initiated immediately after injury.

PMID- 21876822
TI  - Endothelium-derived hyperpolarizing factor and vascular function.
AB  - Endothelial function refers to a multitude of physiological processes that
      maintain healthy homeostasis of the vascular wall. Exposure of the endothelium to
      cardiac risk factors results in endothelial dysfunction and is associated with an
      alteration in the balance of vasoactive substances produced by endothelial cells.
      These include a reduction in nitric oxide (NO), an increase in generation of
      potential vasoconstrictor substances and a potential compensatory increase in
      other mediators of vasodilation. The latter has been surmised from data
      demonstrating persistent endothelium-dependent vasodilatation despite complete
      inhibition of NO and prostaglandins. This remaining non-NO, non-prostaglandin
      mediated endothelium-dependent vasodilator response has been attributed to
      endothelium-derived hyperpolarizing factor/s (EDHF). Endothelial
      hyperpolarization is likely due to several factors that appear to be site and
      species specific. Experimental studies suggest that the contribution of the EDHFs
      increase as the vessel size decreases, with a predominance of EDHF activity in
      the resistance vessels, and a compensatory up-regulation of hyperpolarization in
      states characterized by reduced NO availability. Since endothelial dysfunction is
      a precursor for atherosclerosis development and its magnitude is a reflection of
      future risk, then the mechanisms underlying endothelial dysfunction need to be
      fully understood, so that adequate therapeutic interventions can be designed.

PMID- 21876824
TI  - Predictors of developing significant mitral regurgitation following percutaneous
      mitral commissurotomy with inoue balloon technique.
AB  - Background. Despite the high technical expertise in percutaneous mitral
      commissurotomy (PMC), mitral regurgitation (MR) remains a major procedure-related
      complication. The aim of this work is to find out the most sensitive and
      applicable predictors of development of significant mitral regurgitation (SMR)
      following percutaneous mitral commissurotomy using Inoue balloon technique.
      Methods. We studied prospectively the preprocedural (clinical, echocardiography,
      and hemodynamic) and procedural predictors of significant mitral regurgitation
      (identified as increase of >=2/4 grades of pre-PMC MR by color Doppler flow
      mapping) following valvuloplasty using Inoue balloon in 108 consecutive patients
      with severe mitral stenosis. Multiple stepwise logistic regression analysis was
      performed for variables found positive on univariate analysis to determine the
      most important predictor(s) of developing SMR. Results. The incidence of SMR
      following PMC using Inoue technique was 18.5% (10 patients). MV scoring systems
      were the only variables that showed significant differences between both groups
      (Group A without SMR and Group B with SMR). However, no clinical, other
      echocardiographic measurements, hemodynamic or procedural variables could predict
      the development of SMR. Using multiple regression analysis, the best predictive
      factor for the risk of SMR after Inoue BMV was the total MR-echo score with a
      cutoff point of 7 and a predictive percentage of 97.7%. Conclusions. The total MR
      echo score is the only independent predictor of SMR following PMC using Inoue
      technique with a cutoff point of 7.

PMID- 21876823
TI  - Antioxidant vitamins in the prevention of atrial fibrillation: what is the
      evidence?
AB  - Atrial fibrillation (AF) is the most common sustained arrhythmia that is
      associated with significant morbidity and mortality. Current available therapies
      remain inadequate in symptom control and secondary prevention and are often
      associated with significant side effects. The mechanisms underlying the
      pathogenesis of AF are poorly understood, although electrophysiological
      remodeling has been described as an important initiating step. Recently,
      increasing evidence implicates oxidative stress and inflammation in the
      pathogenesis of AF. We searched the literature for evidence to support the use of
      antioxidant vitamins C and E in the prevention of AF. These vitamins, through
      their reactive-oxygen-species- (ROS-) scavenging effect, have shown a role in AF
      prevention in both animal and small clinical studies. The available evidence,
      however, is currently insufficient to support recommendations for their use in
      the wider patient population. Larger-scale clinical studies are required to
      confirm these preliminary results. Research is also required to further the
      understanding of the processes involved in the pathogenesis of AF and the role of
      antioxidant therapies to prevent the arrhythmia.

PMID- 21876825
TI  - CMR in Heart Failure.
AB  - Heart Failure (HF) is a common syndrome with multiple causes. Cardiovascular
      magnetic resonance (CMR) is a medical imaging technique with significant
      advantages, allowing the understanding of aetiology and pathophysiology of HF in
      the individual patient, permitting specific therapy to be administered and
      predicting prognosis. This paper discusses the diverse role of CMR in HF.

PMID- 21876826
TI  - Where are we heading with noninvasive clinical vascular physiology? Why and how
      should we assess endothelial function?
AB  - There are several invasive and noninvasive methods available to the clinical
      researcher for the assessment of endothelial function. The first investigations
      in humans involved invasive pharmacological vascular function testing, which have
      been used to gain a detailed understanding of the mechanisms involved in the
      pathogenesis of endothelial dysfunction and atherosclerosis as well as novel
      targets for intervention. Techniques for endothelial function testing have
      evolved over time from these invasive methods, which, by their nature, are
      restricted to small studies in the research laboratory, to more standardized
      noninvasive methods, which are suitable for use in large prospective cohort
      studies and clinical trials. This paper describes currently available methods for
      assessment of endothelial function and their potential application in
      cardiovascular research and clinical practice.

PMID- 21876827
TI  - High Throughput ELISAs to Measure a Unique Glycan on Transferrin in Cerebrospinal
      Fluid: A Possible Extension toward Alzheimer's Disease Biomarker Development.
AB  - We have established high-throughput lectin-antibody ELISAs to measure different
      glycans on transferrin (Tf) in cerebrospinal fluid (CSF) using lectins and an
      anti-transferrin antibody (TfAb). Lectin blot and precipitation analysis of CSF
      revealed that PVL (Psathyrella velutina lectin) bound an unique N
      acetylglucosamine-terminated N-glycans on "CSF-type" Tf whereas SSA (Sambucus
      sieboldiana agglutinin) bound alpha2,6-N-acetylneuraminic acid-terminated N
      glycans on "serum-type" Tf. PVL-TfAb ELISA of 0.5 MUL CSF samples detected "CSF
      type" Tf but not "serum-type" Tf whereas SSA-TfAb ELISA detected "serum-type" Tf
      but not "CSF-type" Tf, demonstrating the specificity of the lectin-TfAb ELISAs.
      In idiopathic normal pressure hydrocephalus (iNPH), a senile dementia associated
      with ventriculomegaly, amounts of the SSA-reactive Tf were significantly higher
      than in non-iNPH patients, indicating that Tf glycan analysis by the high
      throughput lectin-TfAb ELISAs could become practical diagnostic tools for iNPH.
      The lectin-antibody ELISAs of CSF proteins might be useful for diagnosis of the
      other neurological diseases.

PMID- 21876820
TI  - Genetics and function of neocortical GABAergic interneurons in neurodevelopmental
      disorders.
AB  - A dysfunction of cortical and limbic GABAergic circuits has been postulated to
      contribute to multiple neurodevelopmental disorders in humans, including
      schizophrenia, autism, and epilepsy. In the current paper, I summarize the
      characteristics that underlie the great diversity of cortical GABAergic
      interneurons and explore how the multiple roles of these cells in developing and
      mature circuits might contribute to the aforementioned disorders. Furthermore, I
      review the tightly controlled genetic cascades that determine the fate of
      cortical interneurons and summarize how the dysfunction of genes important for
      the generation, specification, maturation, and function of cortical interneurons
      might contribute to these disorders.

PMID- 21876828
TI  - Copper modulation as a therapy for Alzheimer's disease?
AB  - The role of metals in the pathophysiology of Alzheimer's disease (AD) has gained
      considerable support in recent years, with both in vitro and in vivo data
      demonstrating that a mis-metabolism of metal ions, such as copper and zinc, may
      affect various cellular cascades that ultimately leads to the development and/or
      potentiation of AD. In this paper, we will provide an overview of the preclinical
      and clinical literature that specifically relates to attempts to affect the AD
      cascade by the modulation of brain copper levels. We will also detail our own
      novel animal data, where we treated APP/PS1 (7-8 months old) mice with either
      high copper (20 ppm in the drinking water), high cholesterol (2% supplement in
      the food) or a combination of both and then assessed beta-amyloid (Abeta) burden
      (soluble and insoluble Abeta), APP levels and behavioural performance in the
      Morris water maze. These data support an interaction between copper/cholesterol
      and both Abeta and APP and further highlight the potential role of metal ion
      dyshomeostasis in AD.

PMID- 21876830
TI  - Genetic risk factors: their function and comorbidities in Alzheimer's disease.

PMID- 21876829
TI  - Cognitive stimulation programs in healthy elderly: a review.
AB  - This literature paper investigated the efficacy of 14 cognitive intervention
      programs administered to healthy elderly participants. PsycINFO and PubMed
      databases were searched using the following terms: cognitive training, cognitive
      stimulation, elderly, and aging. The majority of participants (13/14 studies)
      were recruited in community. Nine out of 14 studies targeted memory as the
      principal cognitive function to train or stimulate. Face-name associations,
      mental imagery, paired associations, and the method of loci were the main
      techniques taught to participants. Improvements were observed on at least one
      outcome measure in each study included in this paper. Recommendations to improve
      cognitive interventions in the healthy elderly are proposed, such as the
      utilization of more robust experimental designs, the inclusion of measures of
      generalization of training in daily life, the assessment of instrumental
      activities of daily living, quality of life, and self-esteem.

PMID- 21876831
TI  - Gene Profiling of Aortic Valve Interstitial Cells under Elevated Pressure
      Conditions: Modulation of Inflammatory Gene Networks.
AB  - The study aimed to identify mechanosensitive pathways and gene networks that are
      stimulated by elevated cyclic pressure in aortic valve interstitial cells (VICs)
      and lead to detrimental tissue remodeling and/or pathogenesis. Porcine aortic
      valve leaflets were exposed to cyclic pressures of 80 or 120 mmHg, corresponding
      to diastolic transvalvular pressure in normal and hypertensive conditions,
      respectively. Linear, two-cycle amplification of total RNA, followed by
      microarray was performed for transcriptome analysis (with qRT-PCR validation). A
      combination of systems biology modeling and pathway analysis identified novel
      genes and molecular mechanisms underlying the biological response of VICs to
      elevated pressure. 56 gene transcripts related to inflammatory response
      mechanisms were differentially expressed. TNF-alpha, IL-1alpha, and IL-1beta were
      key cytokines identified from the gene network model. Also of interest was the
      discovery that pentraxin 3 (PTX3) was significantly upregulated under elevated
      pressure conditions (41-fold change). In conclusion, a gene network model showing
      differentially expressed inflammatory genes and their interactions in VICs
      exposed to elevated pressure has been developed. This system overview has
      detected key molecules that could be targeted for pharmacotherapy of aortic
      stenosis in hypertensive patients.

PMID- 21876832
TI  - Myeloid-related protein activity in rheumatoid arthritis.
AB  - SA100A8, SA100A9, and SA100A12 are members of the myeloid-related protein class.
      SA100A8 and SA100A9, also known as MRP-8 and MRP-14, respectively, are
      intracellular Ca(2+)-binding proteins produced mainly by neutrophils and
      monocytes where they exist as a heterodimeric complex in the cytosol. The MRP-8/
      14 complex has been shown to promote chronic inflammation associated with
      rheumatoid arthritis (RA). In that regard, MRP-8 and MRP-14 regulate the
      inflammatory response through their capacity to recruit neutrophils and monocytes
      to target tissues resulting in attachment to endothelium. MRPs also activate the
      signal transduction pathway principally involving the stress-activated/mitogen
      activated protein kinases. MRP-8/MRP-14 also increased nitric oxide synthesis.
      Most recently, the MRP-8/MRP-14 complex was shown to be a novel ligand for the
      toll-like receptors (TLRs) and TLR-4, in particular. Engagement of TLRs by the
      MRP-8/-14 complex may be particularly important for activating antigen-presenting
      dendritic cells which regulate critical autoimmune responses that promote chronic
      synovitis characteristic of RA.

PMID- 21876833
TI  - A review on current osteoporosis research: with special focus on disuse bone
      loss.
AB  - Osteoporosis is a multifactorial skeletal disorder characterized by decreased
      bone mass and deteriorated microarchitecture that lead to increased risk of
      fracture. The disuse osteoporosis refers to bone mass decrements under conditions
      of decreased mechanical loading, including decreased ground force reaction,
      muscular contraction, and microgravity-related bone loss in astronauts after
      space flights. Although there are many effective treatments available for primary
      osteoporosis, there is a lack of effective treatments for disuse osteoporosis.
      This is because that the aetiology, pathophysiology, and resultant pathology of
      disuse osteoporosis differ from those of primary osteoporosis. The objective of
      this paper is to examine the unique pathology and underlying pathophysiology of
      disuse osteoporosis.

PMID- 21876834
TI  - Bone mineral density accrual determines energy expenditure with refeeding in
      anorexia nervosa and supersedes return of menses.
AB  - Osteopenia and osteoporosis are major complications of anorexia nervosa (AN).
      Since bone is a tissue requiring large amounts of energy, we examined the
      disproportionate increase in resting energy expenditure (REE) that occurs with
      refeeding of AN patients to determine if it was related to bone accretion. Thirty
      seven AN patients aged 23.4 +/- 4.8 years underwent a behavioral weight-gain
      protocol lasting a median of 66 days; 27 remained amenorrheic, and 10 regained
      menses. Sixteen controls aged 25.1 +/- 4.7 years were age- and % IBW matched with
      patients. REE was measured using a respiratory chamber-indirect calorimeter.
      Significant correlations were found between REE and changes in spine (r = 0.48, P
      < 0.02) and leg (r = 0.43, P < 0.05) BMDs in AN patients. Further subgroup
      analysis of the amenorrheics revealed significant correlation between REE and
      change in spine BMD (r = 0.59, P < 0.02) and higher IGF-1 after weight gain
      compared to controls. Amenorrheics also had lower BMDs. These findings were
      absent in the regained menses group. The increase in REE seen in women with AN
      during nutritional rehabilitation may be related to active bone formation, which
      is not as prominent when menses have returned.

PMID- 21876835
TI  - Calcium and vitamin d supplementation in men.
AB  - Calcium and vitamin D supplements reverse secondary hyperparathyroidism and are
      widely prescribed to prevent osteoporotic fractures, with proven antifracture
      efficacy when targeted to individuals with documented insufficiencies. Men who
      should particularly be considered for calcium and vitamin D supplements include
      elderly or institutionalized individuals, patients with documented osteoporosis
      on antiresorptive or anabolic medication, and individuals receiving
      glucocorticoids. Benefits are most apparent when a daily dose of 1000-1200 mg
      calcium is complemented with 800 IU vitamin D. Compliance is the key to
      optimizing clinical efficacy. While (conventionally dosed) vitamin D has not been
      associated with safety concerns, recent meta-analytic data have provided evidence
      to suggest that calcium supplements (without coadministered vitamin D) may
      potentially be associated with cardiovascular risks.

PMID- 21876838
TI  - Recombinant human thyrotropin-aided radioiodine therapy in patients with
      metastatic differentiated thyroid carcinoma.
AB  - Our aim was to test the efficacy of 131-I therapy (RIT) using recombinant human
      TSH (rhTSH) in patients with differentiated thyroid carcinoma (DTC) in whom
      endogenous TSH stimulation was not an option due to the poor patient's physical
      condition or due to the disease progression during L-thyroxin withdrawal. The
      study comprised 18 patients, who already have undergone total or near-total
      thyroidectomy and radioiodine ablation and 0-12 (median 5) RITs after L-thyroxin
      withdrawal. Our patients received altogether 44 RITs using rhTSH while on L
      thyroxin. Six to 12 months after the first rhTSH-aided RIT, PR and SD was
      achieved in 3/18 (17%) and 4/18 patients (22%), respectively. In most patients (n
      = 12; 61%) disease progressed despite rhTSH-aided RITs. As a conclusion, rhTSH
      aided RIT proved to add some therapeutic benefit in 39% our patients with
      metastatic DTC, who otherwise could not be efficiently treated with RIT.

PMID- 21876837
TI  - Levothyroxine treatment in pregnancy: indications, efficacy, and therapeutic
      regimen.
AB  - The prevalence of overt and subclinical hypothyroidism during pregnancy is
      estimated to be 0.3-0.5% and 2-3%, respectively. Thyroid autoantibodies are found
      in 5-18% of women in the childbearing age. The aim of this review is to
      underscore the clinical significance of these findings on the health of both the
      mother and her offspring. Methods of evaluation of thyroid function tests (TFTs)
      during pregnancy are described as are the threshold values for the diagnosis of
      overt and subclinical hypothyroidism or hypothyroxinemia. Anticipated differences
      in TFTs in iodine-sufficient and iodine-deficient areas are discussed and data
      are provided on potential complications of hypothyroidism/hypothyroxinemia and
      autoimmune thyroid disease during pregnancy and adverse effects for the
      offspring. The beneficial effects of levothyroxine therapy on pregnancy outcomes
      and offspring development are discussed with a proposed treatment regimen and
      follow up strategy.

PMID- 21876836
TI  - Thyroid hormone and the neuroglia: both source and target.
AB  - Thyroid hormone plays a crucial role in the development and function of the
      nervous system. In order to bind to its nuclear receptor and regulate gene
      transcription thyroxine needs to be activated in the brain. This activation
      occurs via conversion of thyroxine to T3, which is catalyzed by the type 2
      iodothyronine deiodinase (D2) in glial cells, in astrocytes, and tanycytes in the
      mediobasal hypothalamus. We discuss how thyroid hormone affects glial cell
      function followed by an overview on the fine-tuned regulation of T3 generation by
      D2 in different glial subtypes. Recent evidence on the direct paracrine impact of
      glial D2 on neuronal gene expression underlines the importance of glial-neuronal
      interaction in thyroid hormone regulation as a major regulatory pathway in the
      brain in health and disease.

PMID- 21876840
TI  - Perceived Changes in Communication as an Effect of STN Surgery in Parkinson's
      Disease: A Qualitative Interview Study.
AB  - The aim of the present study was to explore four individuals' perspective of the
      way their speech and communication changed as a result of subthalamic nucleus
      deep brain stimulation treatment for Parkinson's disease. Interviews of two men
      and two women were analyzed using qualitative content analysis. Three themes
      emerged as a result of the analysis. The first theme included sub-themes
      describing both increased and unexpected communication difficulties such as a
      more vulnerable speech function, re-emerging stuttering and cognitive
      difficulties affecting communication. The second theme comprised strategies to
      improve communication, using different speech techniques and communicative
      support, as well as trying to achieve changes in medical and stimulation
      parameters. The third theme included descriptions of mixed feelings surrounding
      the surgery. Participants described the surgery as an unavoidable dramatic
      change, associated both with improved quality of life but also uncertainty and
      lack of information, particularly regarding speech and communication changes.
      Despite negative effects on speech, the individuals were generally very pleased
      with the surgical outcome. More information before surgery regarding possible
      side effects on speech, meeting with a previously treated patient and possibly
      voice and speech therapy before or after surgery are suggested to facilitate the
      adjustment to the new speech conditions.

PMID- 21876841
TI  - Effect of LSVT on Lexical Tone in Speakers with Parkinson's Disease.
AB  - Lee Silverman Voice Treatment (LSVT) has well-documented treatment efficacy for
      individuals with hypokinetic dysarthria associated with Parkinson's disease (PD).
      Positive changes have been noted after treatment not only for vocal loudness but
      also for many other speech dimensions, including intonation (monotonicity). There
      have been few studies investigating the effect of LSVT on lexical tone which,
      like intonation, is controlled by variations in fundamental frequency. This study
      involved 12 Cantonese speakers with idiopathic PD who were enrolled in a standard
      LVST treatment protocol. Speech data were collected 3-4 days before treatment and
      1 day after treatment. A wide variety of perceptual and acoustic variables were
      analyzed. The results showed significant improvements in loudness and intonation
      after treatment, but no significant changes in lexical tone. These results have
      theoretical implications for the relationship between tone and intonation and for
      models of the physiological control of fundamental frequency.

PMID- 21876839
TI  - Sleep disturbances associated with Parkinson's disease.
AB  - Sleep disturbances are common problems affecting the quality life of Parkinson's
      disease (PD) patients and are often underestimated. The causes of sleep
      disturbances are multifactorial and include nocturnal motor disturbances,
      nocturia, depressive symptoms, and medication use. Comorbidity of PD with sleep
      apnea syndrome, restless legs syndrome, rapid eye movement sleep behavior
      disorder, or circadian cycle disruption also results in impaired sleep. In
      addition, the involvement of serotoninergic, noradrenergic, and cholinergic
      neurons in the brainstem as a disease-related change contributes to impaired
      sleep structures. Excessive daytime sleepiness is not only secondary to nocturnal
      disturbances or dopaminergic medication but may also be due to independent
      mechanisms related to impairments in ascending arousal system and the orexin
      system. Notably, several recent lines of evidence suggest a strong link between
      rapid eye movement sleep behavior disorder and the risk of neurodegenerative
      diseases such as PD. In the present paper, we review the current literature
      concerning sleep disorders in PD.

PMID- 21876842
TI  - Molecular bases of cutaneous and uveal melanomas.
AB  - Intensive research in recent years has begun to unlock the mysteries surrounding
      the molecular pathogenesis of melanoma, the deadliest of skin cancers. The high
      penetrance, low-frequency susceptibility gene CDKN2A produces tumor suppressor
      proteins that function in concert with p53 and retinoblastoma protein to thwart
      melanomagenesis. Aberrant CDKN2A gene products have been implicated in a great
      many cases of familial cutaneous melanoma. Sporadic cases, on the other hand,
      often involve constitutive signal transduction along the mitogen-activated
      protein kinase (MAPK) pathway, with particular focus falling upon mutated RAS and
      RAF protooncogenes. The proliferative effects of the MAPK pathway may be
      complemented by the antiapoptotic signals of the PI3K/AKT pathway. After skin,
      melanoma most commonly affects the eye. Data for the constitutive activation of
      the MAPK pathway in uveal melanoma exists as well, however, not through mutations
      of RAS and RAF. Rather, evidence implicates the proto-oncogene GNAQ. In the
      following discussion, we review the major molecular pathways implicated in both
      familial and sporadic cutaneous melanomagenesis, the former accounting for
      approximately 10% of cases. Additionally, we discuss the molecular pathways for
      which preliminary evidence suggests a role in uveal melanomagenesis.

PMID- 21876844
TI  - Role of apoptosis in rabies viral encephalitis: a comparative study in mice,
      canine, and human brain with a review of literature.
AB  - To evaluate the role of apoptosis in rabies encephalitis in humans and canines
      infected with wild-type street virus, in comparison with rodent model infected
      with street and laboratory passaged CVS strain, we studied postmortem brain
      tissue from nine humans, six canines infected with street rabies virus, and Swiss
      albino mice inoculated intramuscularly (IM) and intracerebrally (IC) with street
      and CVS strains. Encephalitis and high rabies antigen load were prominent in
      canine and human brains compared to rodents inoculated with street virus.
      Neuronal apoptosis was detectable only in sucking mice inoculated with CVS strain
      and minimal in street virus inoculated mice. In a time point study in suckling
      mice, DNA laddering was noted only terminally (7 days p.i.) following IC
      inoculation with CVS strain but not with street virus. In weanling and adult
      mice, apoptosis was restricted to inflammatory cells and absent in neurons
      similar to human and canine rabies-infected brains. Absence of neuronal apoptosis
      in wild-type rabies may facilitate intraneuronal survival and replication while
      apoptosis in inflammatory cells prevents elimination of the virus by abrogation
      of host inflammatory response.

PMID- 21876843
TI  - Current concepts on dedifferentiation/high-grade transformation in salivary gland
      tumors.
AB  - The concept of dedifferentiation had previously been used in salivary gland
      carcinomas. Recently, the term "high-grade transformation" was introduced for
      adenoid cystic carcinoma, acinic cell carcinoma, epithelial-myoepithelial
      carcinoma, and polymorphous low-grade adenocarcinoma and may better reflect this
      phenomenon, although transformation into moderately differentiated adenocarcinoma
      (i.e., not "high grade") has also been described. Among the immunohistochemical
      markers, Ki-67 seems to be the only one that can help distinguish between the
      conventional and transformed components; however, the combination of
      morphological criteria is still sovereign. The overexpression of p53 was observed
      in the transformed component in all tumor types studied, despite few cases having
      been demonstrated to carry mutations or deletions in TP53 gene. Genetic studies
      in salivary gland tumors with dedifferentiation/high-grade transformation are
      rare and deserve further investigation. This paper aims at providing an overview
      on the recent concepts in histopathological classification of salivary gland
      tumors, complemented by immunohistochemical and genetic findings.

PMID- 21876845
TI  - The interpretation of phrases used to describe uncertainty in pathology reports.
AB  - Histopathological reports frequently contain phrases describing the degree of
      uncertainty of the diagnosis. We examined the interpretations of such terms by
      cellular pathologists, other doctors, and medical students. 203 respondents
      estimated the degree of certainty they would associate with the following phrases
      in a cellular pathology report: the features are indicative of; raise the
      possibility of; are compatible with; are probably those of; are diagnostic of;
      are in keeping with; and are suggestive of. For all phrases assessed other than
      "diagnostic of", all groups showed a wide spread in the interpreted probability.
      For example, the probability associated with the term "in keeping with" by
      individual consultant pathologists ranged from 25 to 100%. This study
      demonstrates that pathologists vary widely in how they interpret the meaning of
      phrases describing probability that are commonly used in pathology reports. We
      suggest that this potential risk is highlighted during pathology training.

PMID- 21876846
TI  - Limited Therapeutic Time Windows of Mild-to-Moderate Hypothermia in a Focal
      Ischemia Model in Rat.
AB  - Although many studies have shown the great potential of induced hypothermia in
      stroke treatment, we recognize that there are limitations to the protective
      effects of hypothermia even in the laboratory. Here, we review our experiments on
      the protective effects of mild-to-moderate hypothermia in rats. Focal ischemia
      was induced by bilateral common carotid artery (CCA) occlusion for 1 to 2 hours
      combined with permanent or transient middle cerebral artery (MCA) occlusion. We
      compared the effects of mild (33 degrees C) and moderate (30 degrees C)
      hypothermia, evaluated therapeutic time windows, and studied the underlying
      mechanisms. On review, our findings revealed that the protective effects of
      induced mild hypothermia (33 degrees C) were limited, and the therapeutic time
      window of even moderate hypothermia (30 degrees C) was very short in our specific
      models, although this limitation might be due to the relatively brief periods of
      hypothermia used. In addition, we found that hypothermia reduced brain injury by
      preserving Akt activity, PTEN phosphorylation and epsilonPKC activity, while
      inhibiting ROS production, and deltaPKC activity.

PMID- 21876847
TI  - The hyperdense internal carotid artery sign: prevalence and prognostic relevance
      in stroke thrombolysis.
AB  - Introduction. The hyperdense internal carotid artery sign (HICAS) has been
      suggested as a common marker of terminal internal carotid artery (ICA) thrombus
      associated with poor outcomes following thrombolysis. We aimed to investigate the
      prevalence and prognostic significance of the HICAS in an unselected cohort of
      patients receiving intravenous thrombolysis. Methods. Prethrombolysis NCCTs of
      120 patients were examined for the presence of the HICAS and hyperdense middle
      cerebral artery sign (HMCAS). A poor outcome was defined as a discharge Barthel
      score <15 or inpatient death. Results. A HICAS was present in 3 patients (2.5%).
      Prethrombolysis neurological deficits were significantly more severe in patients
      with a HICAS (P = 0.019). HICAS was not significantly associated with a poor
      outcome (P = 0.323). HMCAS was significantly associated with severe
      prethrombolysis neurological deficits (P = 0.0025) and a poor outcome (P =
      0.015). Conclusions. This study suggests that the prevalence of the HICAS may be
      lower than previously reported. The presence of a HICAS was associated with
      severe prethrombolysis neurological deficits in keeping with terminal ICA
      occlusion. The role of the HICAS as a prognostic marker in stroke thrombolysis
      remains unclear.

PMID- 21876849
TI  - Intensity of oestrus signalling is the most relevant indicator for animal well
      being in high-producing dairy cows.
AB  - Full signalling of oestrous behaviour is vital for proper timing of AI and good
      reproductive performance, currently jeopardized by shorter observations of
      oestrus behaviour. Alternative indicators including progesterone (P(4))
      recordings on-farm are tested. Oestrous intensity of 37 heifers (H) and 30 1st
      parity dairy cows (C(1)) either Swedish Red (32) or Swedish Holstein (35) with
      high genetic potential for milk production, was studied in relation to AI. P(4)
      levels in blood or milk were monitored on-farm at 0, 7, and 20 d post-AI with a
      portable ELISA reader (eProCheck(800)). Avoidance distance and body condition
      were scored at day 7, and pregnancy diagnosed by P(4) (day 20) and trans-rectal
      palpation (day 50). More heifers (46%) than C(1)-cows (10%) showed standing
      oestrus (strongest intensity, P < 0.05), leading to higher pregnancy rate at d50
      (72% versus 37% for C1, P < 0.01) and calving rate (H: 64%, C1: 33%, P < 0.05).
      Avoidance distances were short (<1 m), reflecting good human-animal interaction.
      Visually-recorded standing oestrus yielded 4.8 fold higher odds of pregnancy,
      respectively 4.6-fold higher odds of calving. On-farm P4-recordings had
      complementary value yet less accuracy. Intensity of oestrus signalling relates to
      animal well-being, reflected in pregnancy-to-term being a good indicator for
      optimal welfare in high-producing dairy cattle.

PMID- 21876848
TI  - Reduced cardiorespiratory fitness after stroke: biological consequences and
      exercise-induced adaptations.
AB  - Evidence from several studies consistently shows decline in cardiorespiratory
      (CR) fitness and physical function after disabling stroke. The broader
      implications of such a decline to general health may be partially understood
      through negative poststroke physiologic adaptations such as unilateral muscle
      fiber type shifts, impaired hemodynamic function, and decrements in systemic
      metabolic status. These physiologic changes also interrelate with reductions in
      activities of daily living (ADLs), community ambulation, and exercise tolerance,
      causing a perpetual cycle of worsening disability and deteriorating health.
      Fortunately, initial evidence suggests that stroke participants retain the
      capacity to adapt physiologically to an exercise training stimulus. However,
      despite this evidence, exercise as a therapeutic intervention continues to be
      clinically underutilized in the general stroke population. Far more research is
      needed to fully comprehend the consequences of and remedies for CR fitness
      impairments after stroke. The purpose of this brief review is to describe some of
      what is currently known about the physiological consequences of CR fitness
      decline after stroke. Additionally, there is an overview of the evidence
      supporting exercise interventions for improving CR fitness, and associated
      aspects of general health in this population.

PMID- 21876850
TI  - Ovine paratuberculosis: a seroprevalence study in dairy flocks reared in the
      marche region, Italy.
AB  - In order to fulfil the seroprevalence gap on Mycobacterium avium subsp.
      paratuberculosis infection in ovine dairy farms of Marche region (central Italy),
      a stratified study was carried out on 2086 adult female sheep randomly chosen
      from 38 herds selected in Ancona and Macerata provinces. 73.7% flocks resulted
      infected by a commercial ELISA test (Pourquier, France), with a mean
      seroprevalence of 6.29% of sampled sheep in both provinces. A higher number of
      MAP seropositive ewes was recorded in the large herds' consistence than in the
      small and medium herds' consistence (P = 0.0269), and a greater percentage of
      infected sheep was obtained among female at early/late than in peak lactation
      stage (P = 0.0237). MAP infection was confirmed in 12.6% of infected farms by
      faecal culture. The true sheep-level seroprevalence was 15.1% +/- 7.3%.

PMID- 21876851
TI  - Expected clinical applications of circulating tumor cells in breast cancer.
AB  - Tumor cell invasion and intravascular filtration lead to the presence of
      circulating tumor cells (CTCs) in peripheral blood. CTCs have, thus, been counted
      in patients with cancer to analyze metastatic mechanisms or in the hope of
      developing clinical applications for diagnosis and therapy; various CTC-related
      studies have been performed. However, the clinical significance of CTCs remains
      to be established because of the extremely small number of CTCs in peripheral
      blood as compared with the number of blood cells. Technical problems (e.g.
      reproducibility and reliability) in the detection of CTCs also remain to be
      solved. The use of flow cytometric analysis, which can be performed with tumor
      cell markers such as anti-epithelial cell adhesion molecule antibodies and anti
      cytokeratin antibodies and non-tumor-cell markers such as anti-CD45 antibodies
      has enhanced specificity for the detection of tumor cells. The CellSearch
      System((r)) can detect 1 CTC in 7.5 mL of peripheral blood, with high
      reproducibility. Its detection rate and accuracy for CTCs have been confirmed. In
      the United States, clinical trials have used this system to detect CTCs in
      patients with metastatic breast cancer, metastatic colorectal cancer, and
      metastatic prostate cancer, and CTCs have been confirmed to be a useful
      prognostic factor. This system was also suggested to be useful for monitoring
      treatment response in patients with metastatic breast cancer and was approved by
      the United States Food and Drug Administration in 2004. Measuring CTC counts can
      facilitate the early prediction of treatment response and thereby avoid
      unnecessary therapy. CTCs may also be a useful biomarker for molecular targeted
      agents, enabling the identification of patients most likely to respond to a given
      treatment and facilitating treatment selection. However, the widespread use of
      CTC monitoring as a routine examination requires a further improvement in
      measurement sensitivity, the establishment of criteria for quantitative and
      qualitative evaluations, and additional clear-cut evidence supporting the
      clinical significance of CTCs. We expect that CTCs will be established to be a
      new diagnostic and therapeutic index for breast cancer.

PMID- 21876853
TI  - Long-term disease-free survival after surgical resection for multiple bone
      metastases from rectal cancer.
AB  - Bone metastasis of primary colorectal cancer is uncommon. When it occurs, it is
      usually a late manifestation of disease and is indicative of poor prognosis. We
      describe a patient with multiple metachronous bone metastases from lower rectal
      cancer who was successfully treated with multimodal treatment including surgical
      resections and has shown 32 mo disease-free survival. Surgical resection of
      metastatic bone lesion(s) from colorectal cancer may be a good treatment option
      in selected patients.

PMID- 21876854
TI  - Chronic lymphocytic leukemia-associated cholangiopathy.

PMID- 21876852
TI  - Dickkopfs and Wnt/beta-catenin signalling in liver cancer.
AB  - Liver cancer is the fifth and seventh most common cause of cancer in men and
      women, respectively. Wnt/beta-catenin signalling has emerged as a critical player
      in both the development of normal liver as well as an oncogenic driver in
      hepatocellular carcinoma (HCC). Based on the current understanding, this article
      summarizes the possible mechanisms for the aberrant activation of this pathway
      with specific focus on HCC. Furthermore, we will discuss the role of dickkopfs
      (DKKs) in regulating Wnt/beta-catenin signalling, which is poorly understood and
      understudied. DKKs are a family of secreted proteins that comprise at least four
      members, namely DKK1-DKK4, which act as inhibitors of Wnt/beta-catenin
      signalling. Nevertheless, not all members antagonize Wnt/beta-catenin signalling.
      Their functional significance in hepatocarcinogenesis remains to be further
      characterized for which these studies should provide new insights into the
      regulatory role of DKKs in Wnt/beta-catenin signalling in hepatic carcinogenesis.
      Because of the important oncogenic roles, there are an increasing number of
      therapeutic molecules targeting beta-catenin and the Wnt/beta-catenin pathway for
      potential therapy of HCC.

PMID- 21876855
TI  - Assessment of severity of Clostridium difficile infection.

PMID- 21876856
TI  - The Model for End-stage Liver Disease accurately predicts 90-day liver transplant
      wait-list mortality in Atlantic Canada.
AB  - OBJECTIVE: To determine the generalizability of the predictions for 90-day
      mortality generated by Model for End-stage Liver Disease (MELD) and the serum
      sodium augmented MELD (MELDNa) to Atlantic Canadian adults with end-stage liver
      disease awaiting liver transplantation (LT). METHODS: The predictive accuracy of
      the MELD and the MELDNa was evaluated by measurement of the discrimination and
      calibration of the respective models' estimates for the occurrence of 90-day
      mortality in a consecutive cohort of LT candidates accrued over a five-year
      period. Accuracy of discrimination was measured by the area under the ROC curves.
      Calibration accuracy was evaluated by comparing the observed and model-estimated
      incidences of 90-day wait-list failure for the total cohort and within quantiles
      of risk. RESULTS: The area under the ROC curve for the MELD was 0.887 (95% CI
      0.705 to 0.978) - consistent with very good accuracy of discrimination. The area
      under the ROC curve for the MELDNa was 0.848 (95% CI 0.681 to 0.965). The
      observed incidence of 90-day wait-list mortality in the validation cohort was
      7.9%, which was not significantly different from the MELD estimate of 6.6% (95%
      CI 4.9% to 8.4%; P=0.177) or the MELDNa estimate of 5.8% (95% CI 3.5% to 8.0%;
      P=0.065). Global goodness-of-fit testing found no evidence of significant lack of
      fit for either model (Hosmer-Lemeshow c2 [df=3] for MELD 2.941, P=0.401; for
      MELDNa 2.895, P=0.414). CONCLUSION: Both the MELD and the MELDNa accurately
      predicted the occurrence of 90-day wait-list mortality in the study cohort and,
      therefore, are generalizable to Atlantic Canadians with end-stage liver disease
      awaiting LT.

PMID- 21876857
TI  - Diagnostic value of endoscopic and endoscopic ultrasound characteristics of
      duodenal submucosal tumour-like heterotopic gastric mucosa.
AB  - OBJECTIVE: Recent studies have reported that duodenal heterotopic gastric mucosa
      (HGM) has been observed in 8.9% of patients who undergo
      esophagogastroduodenoscopy. However, there are few reports concerning the
      endoscopic and endoscopic ultrasound characteristics of submucosal tumour-like
      HGM in the duodenum. METHODS: Endoscopic, endoscopic ultrasound (EUS) and
      histological findings were analyzed in six patients with submucosal tumour-like
      HGM, which were confirmed by pathological examination of biopsy or endoscopic
      polypectomy specimens. RESULTS: Endoscopically, the lesions appeared as a
      solitary, sessile submucosal tumour-like mass with a depression at the top. In
      four of six patients, small granular structures were found in the depressed area
      of the mass. On EUS, all masses demonstrated a heterogeneous pattern, among which
      four patients presented anechoic areas while two patients showed no anechoic
      areas. All lesions were localized within the mucosa and submucosa on EUS.
      Histologically, they consisted of gastric glands and some dilated glands, and
      were covered with normal duodenal epithelium. In four of six lesions, the tumours
      were composed of gastric-type foveolar epithelium showing papillary growth,
      fundic glands and pyloric glands, while the others consisted of gastric-type
      foveolar epithelium and pyloric glands. CONCLUSION: A heterogeneous pattern on
      EUS and small granular structures on esophagogastroduodenoscopy represent
      valuable diagnostic features of submucosal tumour-like HGM.

PMID- 21876858
TI  - Reducing the risk of severe complications among patients with Clostridium
      difficile infection.
AB  - BACKGROUND: The incidence and severity of Clostridium difficile infections are
      increasing, and there is a need to optimize the prevention of complicated
      disease. OBJECTIVE: To identify modifiable processes of care associated with an
      altered risk of C difficile complications. METHODS: A retrospective cohort study
      (with prospective case ascertainment) of all C difficile infections during
      2007/2008 at a tertiary care hospital was conducted. RESULTS: Severe
      complications were frequent (occurring in 97 of 365 [27%] C difficile episodes),
      with rapid onset (median three days postdiagnosis). On multivariable analysis,
      nonmodifiable predictors of complications included repeat infection (OR 2.67),
      confusion (OR 2.01), hypotension (OR 0.97 per increased mmHg) and elevated white
      blood cell count (OR 1.04 per 109 cells/L). Protection from complications was
      associated with initial use of vancomycin (OR 0.24); harm was associated with
      ongoing use of exacerbating antibiotics (OR 3.02). CONCLUSION: C difficile
      infections often occur early in the disease course and are associated with high
      complication rates. Clinical factors that predicted a higher risk of
      complications included confusion, hypotension and leukocytosis. The most
      effective ways to improve outcomes for patients with C difficile colitis are
      consideration of vancomycin as first-line treatment for moderate to severe cases,
      and the avoidance of unnecessary antibiotics.

PMID- 21876859
TI  - Should albumin be used in all patients with spontaneous bacterial peritonitis?
AB  - Patients with cirrhosis who develop spontaneous bacterial peritonitis (SBP) have
      been reported to experience a high incidence of renal impairment and mortality.
      Renal dysfunction is possibly related to altered systemic hemodynamics that leads
      to decreased effective arterial blood volume. Albumin, a plasma volume expander,
      has been investigated to determine whether it plays a role in patients with SBP.
      The current literature suggests that albumin can reduce renal impairment and
      mortality in high-risk SBP patients, defined as patients with a serum bilirubin
      level of greater than 68.4 MUmol/L, a blood urea nitrogen level of greater than
      10.7 mmol/L or a serum creatinine level greater than 88.4 MUmol/L. The rationale
      for albumin and other volume expanders in SBP is discussed, accompanied by a
      review of the current literature.

PMID- 21876860
TI  - Alternative targets within the endocannabinoid system for future treatment of
      gastrointestinal diseases.
AB  - Many beneficial effects of herbal and synthetic cannabinoids on gut motility and
      inflammation have been demonstrated, suggesting a vast potential for these
      compounds in the treatment of gastrointestinal disorders. These effects are based
      on the so-called 'endocannabinoid system' (ECS), a cooperating network of
      molecules that regulate the metabolism of the body's own and of exogenously
      administered cannabinoids. The ECS in the gastrointestinal tract quickly responds
      to homeostatic disturbances by de novo synthesis of its components to maintain
      homeostasis, thereby offering many potential targets for pharmacological
      intervention. Of major therapeutic interest are nonpsychoactive cannabinoids or
      compounds that do not directly target cannabinoid receptors but still possess
      cannabinoid-like properties. Drugs that inhibit endocannabinoid degradation and
      raise the level of endocannabinoids are becoming increasingly promising
      alternative therapeutic tools to manipulate the ECS.

PMID- 21876861
TI  - Diverticular disease: epidemiology and management.
AB  - Diverticular disease of the colon is among the most prevalent conditions in
      western society and is among the leading reasons for outpatient visits and causes
      of hospitalization. While previously considered to be a disease primarily
      affecting the elderly, there is increasing incidence among individuals younger
      than 40 years of age. Diverticular disease most frequently presents as
      uncomplicated diverticulitis, and the cornerstone of management is antibiotic
      therapy and bowel rest. Segmental colitis associated with diverticula shares
      common histopathological features with inflammatory bowel disease and may benefit
      from treatment with 5-aminosalicylates. Surgical management may be required for
      patients with recurrent diverticulitis or one of its complications including
      peridiverticular abscess, perforation, fistulizing disease, and strictures and /
      or obstruction.

PMID- 21876864
TI  - Palatal and facial veneers to treat severe dental erosion: a case report
      following the three-step technique and the sandwich approach.
AB  - Minimally invasive principles should be the driving force behind rehabilitating
      young individuals affected by severe dental erosion. The maxillary anterior teeth
      of a patient, class ACE IV, has been treated following the most conservatory
      approach, the Sandwich Approach. These teeth, if restored by conventional
      dentistry (eg, crowns) would have required elective endodontic therapy and crown
      lengthening. To preserve the pulp vitality, six palatal resin composite veneers
      and four facial ceramic veneers were delivered instead with minimal, if any,
      removal of tooth structure. In this article, the details about the treatment are
      described.

PMID- 21876865
TI  - Achieving a precise color chart with common computer software for excellence in
      anterior composite restorations.
AB  - Achieving similar features to those on natural teeth is a common problem with
      esthetic restorations. Color matching is a fundamental procedure required to
      perform a predictable composite resin restoration. It is no longer enough to
      measure these criteria with conventional shade guides, which provide the hue and
      chroma, but do not take into account other dimensions of the tooth such as value,
      intensives, opalescence and characterizations. The present article presents a
      simple and effective technique for color selection using a digital photograph of
      the tooth and an image-editing program such as Adobe Photoshop or Picture
      Project. The digital editing of the photograph with two simple steps described in
      this paper reveals the internal structures of the tooth easily. The modified
      photographs highlight the opalescence, white spots, shape of the internal
      mammelons and other features that are not visible at first glance. This procedure
      provides an accurate color chart with which the clinician can begin an esthetic
      restoration process.

PMID- 21876866
TI  - Esthetic rehabilitation of worn anterior teeth with thin porcelain laminate
      veneers.
AB  - Bonded porcelain restorations are a predictable and durable treatment option with
      which not only esthetic appearance but also the strength and function of teeth
      can be re-established. One of the most important issues of today's dentistry is
      the preservation of sound enamel. Following biomimetic principles, employing
      minimally invasive applications and adhesive technologies are of paramount
      importance for successful restorations. The mock-up technique is advised for
      delicate removal of the required space for thin porcelain veneers minimally.
      Besides minimally invasive preparation, long-term success is determined by the
      adhesive quality of the laminate veneers. This case presentation demonstrates
      restoration of anterior dentition where the wear of incisal edges posed a
      negative effect on the smile of the patient. Before bonded porcelain veneers were
      adhesively cemented, incisal lengthening with direct resin composite and gingival
      contouring was performed. By using the mock-up technique, minimal preparations
      were made with the outline ending in enamel only. For cementation of these
      restorations, step-by-step adhesive procedures are presented.

PMID- 21876867
TI  - Is the smile line a valid parameter for esthetic evaluation? A systematic
      literature review.
AB  - The "smile line" is commonly used as a parameter to evaluate and categorize a
      person's smile. This systematic literature review assessed the existing evidence
      on the validity and universal applicability of this parameter. The latter was
      evaluated based on studies on smile perception by orthodontists, general
      clinicians, and laypeople. METHODS: A review of the literature published between
      October 1973 and January 2010 was conducted with the electronic database Pubmed
      and the search terms "smile," "smile line," "smile arc," and "smile design."
      RESULTS: The search yielded 309 articles, of which nine studies were included
      based on the selection criteria. The selected studies typically correlate the
      smile line with the position of the upper lip during a smile while, on average,
      75 to 100% of the maxillary anterior teeth are exposed. A virtual line that
      connects the incisal edges of the maxillary anterior teeth commonly follows the
      upper border of the lower lip. Average and parallel smile lines are most common,
      influenced by the age and gender of a person. Orthodontists, general clinicians,
      and laypeople have similar preferences and rate average smile lines as most
      attractive. CONCLUSIONS: The smile line is a valid tool to assess the esthetic
      appearance of a smile. It can be applied universally as clinicians and laypersons
      perceive and judge it similarly.

PMID- 21876868
TI  - A simple way to plan implant positioning: the "S-technique".
AB  - This study presents a technique for improving implant placements. As is widely
      known, a correct positioning is essential in restoration-driven implants, as well
      as in tilted implants in order to obtain satisfactory final functional and
      esthetic results. To this end, some authors have emphasized the importance of
      using a diagnostic and/or surgical guide to plan the exact implant position. In
      practice, one of the clinical problems faced is how to check the accuracy of the
      template prior to initiating the surgical phase. A simple method called the "S
      Technique" is proposed in order to evaluate and to change, if necessary, the
      projected position of the implants by way of metal rods as radiopaque markers.
      This device is easy to produce and is cost-saving to the clinician and,
      therefore, to the patient. Furthermore, in specific patients, this method could
      also decrease the need for computerized tomography scans and/or radiographs, thus
      reducing health risks for the patient.

PMID- 21876869
TI  - Durability of bleaching results achieved with 15% carbamide peroxide and 38%
      hydrogen peroxide in vitro.
AB  - The aim of this study was to assess the durability of bleaching results achieved
      with (1) 15% carbamide peroxide home bleaching and (2) 38% hydrogen peroxide in
      office bleaching. A total of 231 extracted anterior teeth were randomly divided
      into three groups (n = 77 in each group) with comparable mean baseline L*-values
      (68.24 +/- 0.8): a non-bleached control group A, a 15% carbamide peroxide group B
      (5 bleaching intervals of 8 hours), and a 38% hydrogen peroxide group C (3
      intervals of 15 minutes). Durability of bleaching was assessed by comparing CIE
      L*a*b* data after intervals of 2, 4, 12, and 26 weeks from baseline. Both
      bleaching regimes initially produced a highly significant increase in lightness
      parameter L*, with no significant difference between the respective bleaching
      regimes (B: 68.23 / 72.48; C: 68.32 / 73.25). Six months after starting the
      trial, L*-values for group B yielded no significant differences compared to
      baseline (69.55), whereas L*-values for group C were still significantly raised
      (69.91), despite a highly significant decrease when compared to initial bleaching
      results. In both treatment groups, there was a lasting response to bleaching in
      terms of CIE-a* and -b* value decreases. Results for both home- and in-practice
      regimes were found to be similar for about 12 weeks. However, in-office results
      were longer lasting, despite the shorter treatment intervals. Summarized
      bleaching effects, in terms of delta E values, revealed no significant
      differences between treatment groups and the control group after 6 months,
      indicating an abatement of the bleaching results achieved.

PMID- 21876870
TI  - Hard beta and gamma emissions of 124I. Impact on occupational dose in PET/CT.
AB  - AIM: The hard beta and gamma radiation of 124I can cause high doses to PET/CT
      workers. In this study we tried to quantify this occupational exposure and to
      optimize radioprotection. METHODS: Thin MCP-Ns thermoluminescent dosimeters
      suitable for measuring beta and gamma radiation were used for extremity
      dosimetry, active personal dosimeters for whole-body dosimetry. Extremity doses
      were determined during dispensing of 124I and oral administration of the activity
      to the patient, the body dose during all phases of the PET/CT procedure. In
      addition, dose rates of vials and syringes as used in clinical practice were
      measured. The procedure for dispensing 124I was optimized using newly developed
      shielding. RESULTS: Skin dose rates up to 100 mSv/min were measured when in
      contact with the manufacturer's vial containing 370 MBq of 124I. For an
      unshielded 5 ml syringe the positron skin dose was about seven times the gamma
      dose. Before optimization of the preparation of 124I, using an already reasonably
      safe technique, the highest mean skin dose caused by handling 370 MBq was 1.9 mSv
      (max. 4.4 mSv). After optimization the skin dose was below 0.2 mSv. CONCLUSION:
      The highly energetic positrons emitted by 124I can cause high skin doses if
      radioprotection is poor. Under optimized conditions occupational doses are
      acceptable. Education of workers is of paramount importance.

PMID- 21876871
TI  - Reference value of brachial-ankle pulse wave velocity for the eastern Chinese
      population and potential influencing factors.
AB  - The present study was conducted to obtain reference values for brachial-ankle
      pulse wave velocity (baPWV) and to evaluate influencing factors of baPWV
      according to gender. Using automatic devices, baPWV was measured simultaneously
      in 2095 subjects. A total of 647 healthy subjects, none of whom presented
      atherosclerotic risk factors, were analyzed in the present study. Two different
      statistical methods were used to obtain reference values for baPWV according to
      subject gender and age. The association between baPWV value and gender, as well
      as other features, were analyzed. For male subjects, multiple stepwise analysis
      showed that age, systolic blood pressure (SBP), heart rate (HR), and plasma
      levels of triglycerides (TG) were independent predictors of baPWV. For female
      subjects, age, SBP, HR, and plasma levels of uric acid (UA) were independent
      predictors of baPWV. In male subjects, the upper limits of baPWV values were
      1497.43/1425.00, 1518.67/1513.25, 1715.97/1726.50, 1925.20/1971.90, and
      2310.18/2115.00 cm/s, obtained using two different statistical methods for the
      age ranges of 30-39, 40-49, 50-59, 60-69, and 70 and older, respectively. For
      females, the upper limits of baPWV values were 1426.70/1411.13, 1559.15/1498.95,
      1733.50/1739.00, 1958.63/1973.78, and 2720.80/2577.00 cm/s for the age ranges of
      30-39, 40-49, 50-59, 60-69, and 70 and older, respectively. Aging is the most
      important influencing factor for baPWV value and its effect is more prominent in
      females. The reference values of baPWV according to age and gender may be useful
      for the clinical diagnosis and preventive therapy of cardiovascular diseases.

PMID- 21876872
TI  - Drugs and lifestyle for the treatment and prevention of coronary artery disease:
      comparative analysis of the scientific basis.
AB  - In this article, we compare two strategies for atherosclerosis treatment: drugs
      and healthy lifestyle. Statins are the principal drugs used for the treatment of
      atherosclerosis. Several secondary prevention studies have demonstrated that
      statins can significantly reduce cardiovascular events including coronary death,
      the need for surgical revascularization, stroke, total mortality, as well as
      fatal and non-fatal myocardial infarction. These results were observed in both
      men and women, the elderly, smokers and non-smokers, diabetics and hypertensives.
      Primary prevention studies yielded similar results, although total mortality was
      not affected. Statins also induce atheroma regression and do not cause cancer.
      However, many unresolved issues remain, such as partial risk reduction, costs,
      several potential side effects, and long-term use by young patients. Statins act
      mainly as lipid-lowering drugs but pleiotropic actions are also present. Healthy
      lifestyle, on the other hand, is effective and inexpensive and has no harmful
      effects. Five items are associated with lower cardiac risk: non-smoking, BMI
      <=25, regular exercise (30 min/day), healthy diet (fruits, vegetables, low
      saturated fat, and 5-30 g alcohol/day). Nevertheless, there are difficulties in
      implementing these measures both at the individual and population levels. Changes
      in behavior require multidisciplinary care, including medical, nutritional, and
      psychological counseling. Participation of the entire society is required for
      such implementation, i.e., universities, schools, media, government, and medical
      societies. Although these efforts represent a major challenge, such a task must
      be faced in order to halt the atherosclerosis epidemic that threatens the world.

PMID- 21876873
TI  - Effect of high-fat diets on body composition, lipid metabolism and insulin
      sensitivity, and the role of exercise on these parameters.
AB  - Dietary fat composition can interfere in the development of obesity due to the
      specific roles of some fatty acids that have different metabolic activities,
      which can alter both fat oxidation and deposition rates, resulting in changes in
      body weight and/or composition. High-fat diets in general are associated with
      hyperphagia, but the type of dietary fat seems to be more important since
      saturated fats are linked to a positive fat balance and omental adipose tissue
      accumulation when compared to other types of fat, while polyunsaturated fats,
      omega-3 and omega-6, seem to increase energy expenditure and decrease energy
      intake by specific mechanisms involving hormone-sensitive lipase, activation of
      peroxisome proliferator-activated receptor alpha (PPARalpha) and others.
      Saturated fat intake can also impair insulin sensitivity compared to omega-3 fat,
      which has the opposite effect due to alterations in cell membranes. Obesity is
      also associated with impaired mitochondrial function. Fat excess favors the
      production of malonyl-CoA, which reduces GLUT4 efficiency. The tricarboxylic acid
      cycle and beta-oxidation are temporarily uncoupled, forming metabolite byproducts
      that augment reactive oxygen species production. Exercise can restore
      mitochondrial function and insulin sensitivity, which may be crucial for a better
      prognosis in treating or preventing obesity.

PMID- 21876874
TI  - Triorganotin as a compound with potential reproductive toxicity in mammals.
AB  - Organotin compounds are typical environmental contaminants and suspected
      endocrine-disrupting substances, which cause irreversible sexual abnormality in
      female mollusks, called "imposex". However, little is known about the capability
      of triorganotin compounds, such as tributyltin and triphenyltin, to cause
      disorders in the sexual development and reproductive functions of mammals,
      including humans and rodents. Moreover, these compounds can act as potential
      competitive inhibitors of aromatase enzyme and other steroidogenic enzymes,
      affecting the reproductive capacity of male and female mammals. In this review,
      we discuss the cellular, biochemical, and molecular mechanisms by which
      triorganotin compounds induce adverse effects in the mammalian reproductive
      function.

PMID- 21876876
TI  - The tsunami, solidarity and the social construction of knowledge in nursing.

PMID- 21876875
TI  - Prenatally programmed hypertension: role of maternal diabetes.
AB  - Epidemiological and experimental studies have led to the hypothesis of the fetal
      origin of adult diseases, suggesting that some adult diseases might be determined
      before birth by altered fetal development. Maternal diabetes subjects the fetus
      to an adverse environment that has been demonstrated to result in metabolic,
      cardiovascular and renal impairment in the offspring. The growing amount of
      obesity in young females in developed and some developing countries should
      contribute to increasing the incidence of diabetes among pregnant women. In this
      review, we discuss how renal and extrarenal mechanisms participate in the genesis
      of hypertension induced by a diabetic status during fetal development.

PMID- 21876877
TI  - [Biographies of pregnancy and motherhood in adolescence within rural settlements
      in Rio Grande do Sul].
AB  - The objective of this study was to learn about and understand pregnancy and
      motherhood experiences in adolescence within rural settlements. The study started
      from a qualitative approach supported by the biographic method. Witnesses
      comprised women who experienced pregnancy and motherhood in adolescence. Data
      collection was performed in January and February 2009, by thematic biographic
      interview. The biographies show family trajectories of instability and constant
      moves as well as of precarious housing and employment. Pregnancy acceptance by
      the families of the adolescents is directly conditioned to the partner taking
      over the parenthood of the child and the adolescent mother as partner or spouse.
      The most frequently reported changes in the personal life deriving from pregnancy
      and motherhood were loss of freedom and increase of responsibility. At
      institutional level, it is observed the lack of public policies and,
      consequently, of services addressed to and adequate to health specificities
      within rural settlements.

PMID- 21876878
TI  - [Scholars' perception about hospitalization: contributions for nursing care].
AB  - The objective of this study was to describe scholars' feelings in terms of
      hospitalization, and discuss on their perception about hospitalization. It is a
      qualitative study performed using semi-structured interviews and recordings based
      on the following atopic for analysis: feelings and perceptions reported by
      scholars during hospitalization. It was found that the feelings reported by
      scholars during hospitalization are those of restriction, fear, pain,
      preoccupation, missing home and others, and anxiety. Most scholars see
      hospitalization as something negative, though they also report positive aspects
      such as receiving exclusive affection from their mothers, having access to foods
      they usually do not have at home and compensations they receive for being ill.
      Playing emerged as an important activity that alleviates the negative aspects of
      hospitalization. In conclusion, despite having negative feelings, scholars are
      able to realize that hospitalization is important for their recovery.

PMID- 21876879
TI  - [The effectiveness of using semipermeable membrane in preterm infants to reduce
      transepidermal losses].
AB  - An investigation was made on the effectiveness of using semipermeable membrane on
      the skin of preterm infants on the evolution of weight loss and blood glucose
      values, water share, urine specific gravity and sodium. This is an experimental
      study, of the randomized clinical trial type, carried out from March to August
      2008 in the Neonatal Intensive Care Unit of the Teaching Maternity Assis
      Chateaubriand (TMAC) in the city of Fortaleza-Ceara. The sample consisted of 42
      preterm infants. The data were presented in tables and charts. In the application
      of the semipermeable membrane, the preterm infants of the intervention group (IG)
      had a decrease in the sodium levels and the daily flow demands, they also
      presented fewer hyperglycemia episodes and the urinary density was kept within
      normal patterns. The semipermeable membrane is, in fact, an effective therapeutic
      resource to minimize transepidermal water losses.

PMID- 21876880
TI  - [The vulnerability experienced by the family of children hospitalized in a
      pediatric intensive care unit].
AB  - The objective of this study was to understand the vulnerability experienced by
      the family of children hospitalized in a Pediatric Intensive Care Unit (PICU).
      The Symbolic Interactionism and the Concept of Family Vulnerability were the
      frameworks used to understand this experience. Qualitative Content Analysis was
      used. Data was collected through interviews and observation with 11 families of
      children hospitalized in a PICU of a university hospital in Sao Paulo. Six
      analytical categories regarding the family experience emerged. The categories
      were compared to the conceptual categories of Family and Vulnerability, and
      revealed the elements that defined the concept within this context. The child's
      hospitalization in a PICU triggers intense suffering within the family, as it
      refers to the possibility of losing their child. Thus, the power and the autonomy
      of the family in relation to their child are reduced, intensifying the feeling of
      vulnerability.

PMID- 21876881
TI  - [Postoperative pain in children: a gender approach].
AB  - The objective of this study was to verify and describe, from a gender focus, the
      associations between gender and specific postoperative pain variables in
      pediatrics. This is a cross-sectional study of 77 children between 6 and 13 years
      of age (M=9 years; sd=2.2 years), ASA I and II, 77.9% from low-income classes,
      68.8% boys and 32.8% girls. Data were collected on the first postoperative (1st
      PO) day through semi-structured interviews and four measurement scales. The main
      baseline diseases were adenotonsillitis and fractures. Prevalence of pain on the
      1st PO was 91.7% for girls and 75.5% for boys (p>0.05). No association was found
      between pain intensity and gender. The most used pain descriptors were it cuts
      and it squeezes. The preferred scale was the EFMC (with faces from a Brazilian
      cartoon: Monica's Gang). Pediatric pain management is still inadequate and gender
      may influence the pain response.

PMID- 21876882
TI  - [Understanding nurses' awareness as to the use of therapeutic play in child
      care].
AB  - The objective of this study was to understand how nurses become aware of the use
      of therapeutic play as a nursing intervention instrument. Symbolic Interactionism
      was the theoretical framework and Interpretive Interactionism was used as the
      methodological framework. Participants were seven nurses working at hospitals and
      outpatient pediatric units who used the therapeutic play in their practice. Four
      representative themes emerged: Expanding the way he/she sees the child; Becoming
      fascinated with a new possibility to provide care; Noticing his/her revalidated
      action; and Committing himself/herself to the theme development. Such themes
      revealed that when nurses become acquainted with therapeutic play and use it in
      his/her practice, they begin on a journey that allows him/her to recognize the
      benefits of this intervention. By doing so, nurses revalidate their actions more
      and more, thus valuing play as a nursing intervention tool. The authors believe
      that teaching about therapeutic play and integrating it to nurses' daily practice
      are challenges yet to be overcome.

PMID- 21876883
TI  - [Communication and education in health consultations to children with acute
      respiratory infections].
AB  - The objective of this study was to identify the recommendations for the care of
      children with acute respiratory infections (ARI) and to describe the process of
      communication between professionals and mothers during the consultation. Data
      collection was performed in Primary Care Units, through interviews and
      observation of physicians' and nurses' consultations to children with ARI. The
      recommendations ranging between professionals and were incomplete and focusing on
      the disease, mainly on the treatment; communication is focused on the
      professional, which does not promote an emancipatory education process. The
      results confirmed the need to include such issues in the initial and ongoing
      training of professionals.

PMID- 21876884
TI  - [Locus of control in health and self-esteem in type-2 diabetic patients].
AB  - The objective of this study was to relate the scores obtained with the
      application of the scales of locus of control of health and self esteem with
      socio-demographic and clinical variables, risk factors and chronic complications
      in 65 patients with type-2 diabetes mellitus. This is a descriptive cross
      sectional study. Statistical analysis was performed using Pearson's chi-square,
      Mann-Whitney, Kruskal-Wallis, and Spearman's Correlations tests. Regarding the
      locus of control, in average, patients presented higher scores in the internal
      dimension, and women showed more externality-at random for health. Statistically
      significant relationships were found between internality with time of diagnosis
      and physical activity; between externality-other powerful entities with glycated
      hemoglobin and physical activity; and between externality-at random with practice
      of physical activity. Most individuals has high self-esteem, but no variable was
      statistically related.

PMID- 21876885
TI  - [Knowledge and attitudes of patients with diabetes mellitus in a primary health
      care system].
AB  - The objective of this study was to characterize patients with type 2 diabetes
      mellitus, according to sociodemographic and clinical variables, and to analyze
      scores of knowledge and attitudes regarding the disease. Participants were 79
      users who received care in a primary health care service, in 2008. The Diabetes
      Mellitus Knowledge (DKN-A) and Attitude (ATT-19) questionnaires were used for
      data collection. The population was formed by adults and elderly adults, who were
      between 30 and 80 years old. Most were literate (96.3%); married (63.3%); female
      (63.3%) and classified as class-2 obesity. As to the knowledge about the disease,
      subjects obtained scores lower than 8, indicating unsatisfactory results on self
      care. Scores obtained regarding attitudes show difficulties to cope with the
      disease. Results evidence the need to adopt a Diabetes Education Program at the
      studied unit.

PMID- 21876886
TI  - [Living older in the family context: dependency in self-care].
AB  - The purpose of this study is to help improve nursing care to dependent people and
      their families. The study objectives were: to describe the degree of dependency
      of the elderly in the family context; to identify the sociodemographic
      characteristics of the dependent elderly in the family context; to describe the
      main cause of dependency in the aged at home. This is a exploratory, descriptive
      study with a quantitative approach. In the period comprised between October 2007
      and June 2008, 108 families from a northern region of Portugal were selected,
      with an elderly dependent. It was a convenience sample. For the collection of
      information, we used a questionnaire with the Barthel Index. Results showed that
      older people are predominantly women, widows, in average 81 years old, with
      severe level of dependence, and the leading cause of dependence was circulatory
      system diseases.

PMID- 21876887
TI  - [Responsibility in health care: regarding the time we live as intensive care
      nurses].
AB  - This qualitative investigation was supported by Foucault's analysis with emphasis
      on the notion of governability, and had the following objectives: to analyze the
      relationship between techno-biomedicine and bioethics as discourses of the
      contemporaneousness implied in the production of nurses' subjectivity within the
      context of the Intensive Care Unit (ICU); and approach the responsibility implied
      in health care as one of the unfolding strategies of technology of speech of
      bioethics and biotechnology, creating certain forms of the nurse understanding
      and intervening in the Intensive Care Unit (ICU). From the perspective of the
      multiple ways that can emerge when analyzing a critical reading of analyzed texts
      and interviews with nurses, responsibility in health care was unfolded into
      categories that expressed the responsibility in front of new languages and of
      nursing as a guardian of certain attributes in the Intensive Care Unit (ICU).

PMID- 21876888
TI  - [Influence of social support on the quality of life of family caregivers while
      caring for people with dependence].
AB  - The objective of this study was to evaluate the Quality of Life (QOL) of family
      caregivers of handicapped people attended at home by Family Health Teams and the
      relationship with their social support. Sixty-six family caregivers were
      interviewed using the WHOQOL-bref for a QOL evaluation and Zarit Burden Interview
      for the burden. The Social Relations domain of the WHOQOL-bref received the
      second best score within the domains of the instrument. During multiple linear
      regressions analysis, female caregivers, with low burden scores and who had
      received help from someone to perform the care, obtained the highest scores.
      Similarly, caregivers with partners had higher mean scores in the overall global
      assessment for QOL and health than those without partners. The results provide
      evidence of the influence of social support regarding Quality of Life and the
      burden perceived by family caregivers.

PMID- 21876889
TI  - [Municipal health council compositions in the state of Sao Paulo].
AB  - This article discusses the legal structure of the municipal Health Councils in a
      Health County in the state of Sao Paulo comprising six municipalities. This
      descriptive and exploratory study was based on documental research according to
      federal laws for the creation, organization, structure and routine work of the
      health councils. Results were presented and discussed in categories. The health
      councils were created in 1991, and four of them have changed their legal
      instruments, two of them have innovated in some procedures, such as election of
      the director, administration non-coincident with local majors, administrative
      structure and commissions. Some council regulations are in disagreement with
      local and federal laws, such as the deliberative character, parity representation
      of users, internal regiment, municipal staff in charge of council directory, and
      no guarantee of administrative and financial support for routine work. It can be
      concluded that it is necessary to improve and correct regulations to guarantee a
      suitable performance of health councils and also to improve the discussion about
      social participation in the nursing curriculum.

PMID- 21876890
TI  - [The front door of the Ribeirao Preto health system for diagnosing tuberculosis].
AB  - The first contact of TB (tuberculosis) patients with the health system occurs at
      the front door and is essential to access to diagnosis. The objective of this
      study was to identify and analyze patients' first contact with the health system
      for TB diagnosis in Ribeirao Preto. The study was based on an instrument of the
      Primary Care Assessment Tool, adapted for TB care in Brazil. Structure interviews
      were conducted with 100 TB patients diagnosed between June 2006 and July 2007. Of
      all patients, 61% were referred to the diagnosis place and only 29% sought the
      service spontaneously; 66% sought for primary care services, and 34% for
      secondary and tertiary services. Public services diagnosed 89% of all cases, 44%
      of which were diagnosed in emergency services. A total 88% of patients were not
      from the area covered by the service. Although patients have sought for primary
      care services, close to their houses, the diagnosis occurred in secondary and
      tertiary health care.

PMID- 21876891
TI  - [The community health agent and working as a team: the easy and difficult
      aspects].
AB  - The objective of this study is to analyze the easy and difficult aspects of
      teamwork according to community health agents. Qualitative analysis was carried
      out from the hermeneutical and dialectic perspective; the reference point was the
      senses interpretation method. The strengths and weaknesses they pointed out
      revealed that working as a team requires emotional relationships, with emphasis
      on communication, respect and cooperation, and that team meetings is an important
      strategy to achieve this. In conclusion, there is a need for continuous
      investments in team member relationships.

PMID- 21876892
TI  - [Psychosocial care center users and their experience of living with a mental
      illness].
AB  - With a view to the changes in psychiatric care, the objective of this study was
      to learn about the opinion of patients, users of a Psychosocial Care Center,
      about their treatment, their experience of living with a mental illness and its
      psychosocial implications. The results were then matched with their social
      demographic and clinic profile. A descriptive exploratory study was performed,
      where 65 patients with mental illnesses being treated in a center in
      Pindamonhangaba-SP and 53 of their relatives answered a semi-structured
      questionnaire. The results showed that patients with mental illnesses and family
      problems recognize that the disease has changed their lives, but their opinion
      differ about the degree of difficulties they have in doing their everyday
      activities. Although they have been treated for years through this extra-hospital
      individualized system, they know little about their disease. It was observed that
      62% of them have severe diseases, but both groups showed a special ability of
      dealing their adversities. This study contributes with important information for
      mental health nursing practitioners.

PMID- 21876893
TI  - [Reduced version of the scale of attitudes towards alcohol, alcoholism, and
      alcoholics: primary results].
AB  - This study aimed to analyze the items of the Scale of Attitudes toward Alcohol,
      alcoholism and alcoholics in order to prepare a reduced version keeping the
      instrument's psychometric properties. The preliminary version of the Scale
      composed by 165 items was tested in a sample with 144 nursing student. The
      evaluation process of the items consisted of the total-item coefficient
      correlation and reliability of the instrument was estimated by Cronbach's alpha
      coefficient. Results indicate the permanence of 83 items, divided into five
      factors that showed satisfactory values in the different coefficients of internal
      consistency. Further studies are needed with larger samples in order to give
      continuity to the process of scale validation among health professionals.

PMID- 21876894
TI  - [Family health nurse in the Amazon: concepts and management of themes regarding
      alcohol use].
AB  - The objective of this study is to identify the concept that nurses in the Amazon
      have on alcohol abuse and the forms used for management. Focal group and
      individual interviews were performed with all nurses of twelve family health
      teams from a city in the Amazon. It was observed there was a lack of university
      degrees, continuing education and of support/reference - counter - reference
      towards the dimension of alcohol use in the studied population. There is need to
      reform nursing courses and perform continuing education for family health team
      members, and provide them with the necessary support regarding this important
      theme and its consequences, for individuals and their families, as well as for
      the society as a whole.

PMID- 21876895
TI  - [Profile of students entering the nursing diploma program: University of Sao
      Paulo at Ribeirao Preto College of Nursing].
AB  - The objective of this study is to describe the profile of the entering students
      as to gender, age, marital status, educational background (elementary and high
      school studies) and employment status of the first class of the Nursing Teaching
      Diploma Program in EERP/USP, in the year 2006, highlighting their implications
      for the teaching-learning process. This descriptive exploratory study used a
      questionnaire for data collection. Results are presented in a descriptive way,
      with absolute and percentage frequency. The age group of the students is diverse,
      varying from 19 to 46 years old, most (67.5%) of them comes from public schools
      (high school studies), 42% work, of those, 67% already work in the health area.
      These data can influence in the pedagogical practice of professors.

PMID- 21876896
TI  - [Development of educational hypermedia to teach an arterial blood pressure
      measurement procedure].
AB  - Arterial blood pressure measurement is an essential conduct to evaluate the
      condition of the cardiovascular system. Digital teaching environment is a
      powerful tool for the teaching-learning process, because it adds meaning and
      concreteness to the content to be learned, and it can be useful to instruct this
      procedure. The objective of this study was to create educational hypermedia for
      teaching arterial blood pressure measurement, and to describe the steps of that
      creation process. The pedagogical framework of Robert Gagne was used; and the
      construction followed the model proposed by Price. The final product presents
      videos, photos, animations and simulations that demonstrate and teach the
      procedure. Although hypermedia construction has been difficult to use, it can
      positively enhance the teaching of nursing procedures.

PMID- 21876897
TI  - [Getting to know former students of PROFAE nursing courses].
AB  - The PROFAE (Professionalization Project in Nursing) was a relevant initiative for
      professional education. The objectives were to describe the profile of the former
      students of the technical nursing course of the Sao Paulo Health Department
      training centers so as to evaluate the effects of the course for the mobility and
      professional performance in the working market. Data collection was performed
      using a questionnaire answered by 216 former students and four focal groups with
      former students and nurse supervisors. Most respondents were women, with an
      average age of 42.2. The course received a positive evaluation, and two aspects
      were pointed out as motivating for searching for it: institutional support and
      COREN's resolutions. The former students perceive they had more initiative and
      theoretical preparation after the course. Nursing aide remains as the most common
      position in the area, thus causing dissatisfaction, because, especially in public
      services, technician positions are not available.

PMID- 21876898
TI  - [Nurses' autonomy and vulnerability in the Nursing Assistance Systematization
      practice].
AB  - The objective of this study was to recognize the autonomy and vulnerability of
      nurses in the implementation of the Sistema da Assistencia de Enfermagem (SAE)
      Nursing Care System through an integrative literature review, using content
      analysis. A survey was conducted, and 40 articles published between 1998 and 2008
      were selected based on their relevance. Results showed two main categories of
      meaning: Benefits associated to the SAE practice (to patients, to the profession
      and to the institution) and Determinants for the Implementation of SAE (nurse's
      competence, training and education, record-instruments, infrastructure and
      collective sharing-construction). From the integration of the two categories, the
      highlights were the autonomy in acting with freedom and responsibility, science
      based decision-making, and being valued for their social work, as well as the
      vulnerability expressed by interpersonal relationships, the wear generated by
      professional stress and the risk inherent to the service.

PMID- 21876899
TI  - [Communication conceptions in hospital nursing management between head nurses in
      a university hospital].
AB  - The objective of the following study was to analyze the conceptions that head
      nurses of a university hospital have about nursing communication management. It
      is a descriptive-exploratory study with an interpretative qualitative approach.
      The set of data was produced between September and October 2007 through
      interviews with 19 head nurses in a university hospital in Southern Brazil and
      submitted to thematic analysis. The nurses recognize the relevance of
      communication in nursing management, but have different perceptions: part of the
      research group understands communication from its interactive and dialogical
      perspective; others understand formal communication, based on the transmission
      and maintenance of standards and hospital routines, with emphasis on written
      communication. Further discussion about the triad communication, management and
      dialogue is required in order to build more interactive forms of hospital nursing
      care management.

PMID- 21876900
TI  - [American participation in the creation of a nurse model in Brazilian society in
      the 1920's].
AB  - The objectives of this historical-social study are: to describe the circumstances
      that determined the participation of North American nurses in the formation of
      the Brazilian nurse; and analyse the process of implementing institutional
      rituals as a strategy of symbolic fight, to confer visibility to the nurse
      profession and discuss the symbolic effects of institutional rituals for the
      consecration of a nurse model for Brazilian society at the time. The primary
      sources are constituted of pertaining written and photographic documents relative
      to the studied theme. By reading the documentary corpus an analysis was made of
      the symbols that had distinguished and established the hierarchies of the
      actions, as well as the strategies undertaken for the North American nurses,
      towards implementing a new model of nurses in Brazilian society, coherent with
      the model of the North American schools of nursing. Institutional rituals,
      conducted or testified by prestigious figures of the history of Brazil and
      nursing, were fundamental for the construction of professional identity.

PMID- 21876901
TI  - [Dialogues in psychology and nursing in a time of shifting paradigms].
AB  - Currently, we are experiencing a paradigm shift in relation to how we understand
      health and care. The biomedical model has been replaced by a vision of an
      integral being, and care emphasis is being placed on health promotion and disease
      prevention. However, the discourse of personal responsibility for health can
      generate in patients feelings of guilt, shame, fear and paranoia, while in
      professionals it can cause feelings of powerlessness and frustration. These
      feelings disrupt attachments and, thus, reduce the effectiveness of care. The
      objective of this theoretical study is to propose a dialogue between Psychology,
      with social constructionist sensitivity, and Nursing, to examine the
      possibilities of improving care from this approach. As an alternative to the
      discourse of personal responsibility, relational responsibility and understanding
      health and care in the long time, lived time and short time, is proposed.

PMID- 21876902
TI  - [Higher education in nursing: between symbolic domination and political
      emancipation].
AB  - In this reflection we problematize the action of caring and teaching how to care
      in nursing based on some of Pierre Bourdieu's concepts about domination and
      symbolic power. The basic tenet of this work was to think of education as
      something vital for our existence on Earth. In this article, we used Pedro Demo's
      ideas as a reference to talk about education, which is understood as a developer
      of political subjects and as something far beyond formal knowledge management. It
      is the very first base on which human autonomy is built, and it leads to a
      constant growth of opportunities to exercise citizenship, qualifying our everyday
      existence. In the academic context, where health, education and nursing are all
      gathered, the competent, critical and reflective teaching work can be highly
      institutive praxis.

PMID- 21876903
TI  - [The HIV/AIDS vulnerability framework applied to families: a reflection].
AB  - The objective of this study is to reflect upon the vulnerabilities experienced by
      the families dealing with the Human Immunodeficiency Virus/Acquired
      Immunodeficiency Syndrome (HIV/Aids), and is based on the pertinent literature.
      To do this, we attempted to propose consideration related to the plurality of
      families in contemporaneity, and present the understandings and development
      regarding the vulnerability framework to the Aids epidemics. Finally, the study
      presents a description of the reflections made about the vulnerabilities to HIV
      and/or falling ill with Aids to which the families are exposed to in their
      personal, social and pragmatic levels. In conclusion, it is emphasized that
      knowing these specific vulnerabilities experienced by the families is essential
      in order to guide and develop the health care actions.

PMID- 21876904
TI  - [Psychoeducational group and bipolar affective disorder: a reflection on the
      asylum and psychosocial models].
AB  - Bipolar Affective Disorder (BAD), known by its chronicity, complexity and high
      rates of morbidity and mortality, is one of the main causes of disability in the
      world. There is growing evidence that its path can be changed by psychotherapy
      approaches, such as psychoeducation, which improves one's social and occupational
      behavior and capacity to deal with stressful situations. This study is an
      experience report about a psychoeducational group for individuals with BAD and
      their relatives, which consisted on reflecting upon the components of the mental
      health practice paradigm. Reflecting upon the psychosocial and asylum ways
      regarding the conceptions of object and mode of work permitted to locate the
      group in a psychosocial manner, as knowledge and experience favor the autonomy of
      the individuals, who have more chances to face the difficulties that occur in
      their suffering-existence process.

PMID- 21876905
TI  - [Infection control related to central venous catheter impregnated with
      antiseptics: an integrative review].
AB  - The use of central venous catheter is pointed out as a risk factor to blood
      stream infection. The objective of this study was to reach scientific evidence on
      infection control related to central venous catheter impregnated with
      antiseptics, used in hospitalized adult patients. Studies were selected from the
      LILACS, CINAHL and MEDLINE databases. Nine articles were selected by means of
      integrative literature review. The publications on the use of catheters
      impregnated with antiseptics showed statistically significant differences
      regarding the reduction of microbial colonization; however, only one study showed
      reduction in the occurrence of infection. The analysis of the studies revealed
      there is a need for further research in different patient populations in order to
      obtain general conclusions.

PMID- 21876906
TI  - [Nursing staff absenteeism rates as a personnel management indicator].
AB  - Absenteeism in nursing is a difficult problem for health organizations; hence it
      is an indicator that must be monitored. The objective of this study was to
      analyze the absenteeism rate of nursing professionals in a public hospital.
      Absenteeism data were collected monthly, from January to July 2008, and
      calculated by means of an electronic program. The mean absenteeism index for
      nurses varied from 5.6% to 9.7% for technicians/nursing aides. Sick leaves were
      the most prevalent reason for absences. The data revealed the major cause of
      absenteeism and pointed at the need to change policies for hiring nursing
      professionals, in addition to reviewing the working processes in order to improve
      the workers' health conditions.

PMID- 21876907
TI  - [Computerized system for managing nursing care indicators at Hospital Sao Paulo].
AB  - Indicators are tools that permit to define parameters that will be used to make
      comparisons between a result and its expected value, as well as to add a value of
      judgement in this regard. The purpose of this study is to describe the experience
      of a group of nurses in the development of a computerized system to manage
      nursing care indicators at Hospital Sao Paulo. Four stages were used to implement
      the indicator management system: developing a nursing care indicator handbook;
      performing a manually registered pilot test; developing the computerized system;
      and performing the pilot test of the computerized system in eleven units at the
      hospital.

PMID- 21876908
TI  - [A contribution to occupational health: a guide on the exposure to biological
      fluids].
AB  - Health workers are exposed to occupational hazards at the workplace, among which
      we highlight the biological risk. Information and orientation should be provided
      regarding the conduct that workers are expected to follow in the case becoming
      exposed. Thus, this guide is intended to provide the elements to orient workers'
      conduct in cases of biological exposure, improving adherence to the monitoring
      protocol.

PMID- 21876909
TI  - The title: herald of scientific communication.

PMID- 21876911
TI  - So, now what? what are the risks of breast cancer and myocardial infarction among
      women receiving hormonal replacement therapy after menopause?

PMID- 21876912
TI  - What are the most frequent complications of Fobi-Capella bariatric surgery and
      how to treat them?

PMID- 21876913
TI  - Is laparoscopic cholecystectomy safe in patients with liver cirrhosis?

PMID- 21876914
TI  - Asthma in childhood: drug therapy.

PMID- 21876915
TI  - Embolic pulmonary complication of a cerebral arteriovenous malformation
      treatment.

PMID- 21876917
TI  - Well-being and help-seeking: an exploratory study among final-year medical
      students.
AB  - OBJECTIVE: Doubts, competitiveness and preparation for the residency examination
      increase stress and insecurity at the end of medical course. Well-being is very
      important at this point, but it is known that medical students are reluctant to
      seek help, particularly for emotional problems. This study investigated the
      relationship among well-being, perceived needs and help-seeking in final-year
      students. METHODS: Well-being was assessed using Beck's Inventories of Anxiety
      (BAI) and Depression (BDI) and the WHOQOL-brief (quality of life). A
      questionnaire was used to assess perceived needs and medical school support
      resources. RESULTS: The students reported good quality of life (68%) but
      presented anxiety (27%), depression (20%) and impaired social functioning. Fifty
      one percent of the students acknowledged academic needs and 25% psychological
      needs. Only a portion of the students with anxiety and depression or bad quality
      of life used the institutional support. Female gender, perceived psychological
      needs and anxiety symptoms were associated to the use of the Mental Health
      Service. Satisfaction with mentoring relationships and positive changes were
      associated to Mentoring attendance. CONCLUSION: There are different factors
      involved in help-seeking and identifying specificities in the use of
      institutional support resources can help to develop strategies to sensitize
      students about help-seeking during the medical course.

PMID- 21876918
TI  - Correlation of spirometry with the six-minute walk test in eutrophic and obese
      individuals.
AB  - OBJECTIVE: To assess the distance covered by both eutrophic individuals and
      individuals with different grades of obesity and correlate the data obtained with
      spirometric values. This study is justified by the existing difficulty in
      assessing the functional capacity in obese individuals, and by the low cost and
      good specificity of six-minute walk test (6MWT) in predicting reduced capacity
      for activities of daily living for any individual. METHODS: One hundred fifty
      four individuals of both genders were assessed after being divided into two
      groups: G1, obese individuals (n = 93, BMI >= 30 kg/m2) and G2, eutrophic
      individuals (n = 61, BMI 18.5 to 24.99 kg/m2). The 6MWT was performed using the
      methodology described by the American Thoracic Society (ATS-2002). Spirometry was
      performed both before and after the application of a bronchodilator agent (BDA)
      in accordance with the Guidelines for Pulmonary Function Tests by the Brazilian
      Society of Pneumology and Phthisiology (SBPT-2002). The statistical analysis,
      consisting of mean, standard deviation, Pearson's correlation, Student's t test
      and Spearman's correlation, considered p < 0.05. RESULTS: The 6MWT analysis with
      spirometry for G1 was positively correlated only with pre- and post-BDA peak
      expiratory flow rate (PEFR). CONCLUSION: The present study showed a positive
      correlation between pre- and post-BDA PEFR and the distance covered in the 6MWT
      in obese subjects, that is, the higher the PEFR, the higher the physico
      functional capacity of the individual, and consequently, the greater the distance
      covered.

PMID- 21876920
TI  - [Influence of maternal and neonatal factors on bronchopulmonary dysplasia
      development].
AB  - OBJECTIVE: To review epidemiological features of bronchopulmonary dysplasia (BPD)
      and its relationship with maternal and neonatal conditions in a neonatal unit.
      METHODS: Cross-sectional, descriptive and analytical study involving preterm
      newborns (NBs) with a birth weight lower than 1,500 g and gestational age under
      37 weeks. Data was collected through a review of medical records of these
      newborns admitted to a neonatal unit. RESULTS: The study included 323 newborns
      with a mean birth weight of 1,161 g (+/- 231 g), gestational age between 24 and
      36.5 weeks, with a BPD incidence of 17.6%. Among the NBs developing BPD, the mean
      of days using invasive mechanical ventilation (IMV), non-invasive ventilation
      (NIMV), and supplemental oxygen was 17.6, 16.2, and 46.1 days, respectively, with
      a time significantly longer for those NBs developing BPD (p < 0.001). BPD
      occurred significantly more often in NBs with a patent ductus arteriosus (PDA).
      CONCLUSION: BPD incidence in this study was similar to that found in the
      literature. No BPD association with maternal infection and antenatal
      corticosteroid use was found. NBs receiving exogenous surfactant had a higher BPD
      incidence because they had lower BW and GA. Concomitant occurrence of PDA and BPD
      is associated with staying longer on IMV, NIMV and supplemental oxygen.

PMID- 21876919
TI  - Safety of a training program for ultrasound-guided internal jugular vein
      catheterization in critically ill patients.
AB  - OBJECTIVES: Evaluate the safety and effectiveness of a training program for
      performing ultrasound-guided internal jugular vein cannulation in critically ill
      patients. METHODS: Cohort prospective study, evaluating adult patients admitted
      in a teaching intensive care unit (ICU). Catheter placement was performed by an
      ICU medical resident. The patient's baseline characteristics, vessel's position
      and operator experience were the evaluated variables. The main outcomes were
      cannulation success rate and incidence of major complications. RESULTS: A total
      of 118 consecutive patients were enrolled between May 2008 and November 2009. The
      success rate of ultrasound guided catheter placement was 90% (106/118), 77% in
      the first attempt. Major complications occurred in 4% of the cases (n = 5) and
      were not associated with the analyzed variables. Inability to place the guide
      wire was the reason for 58% (7/12) of the failures. Operators with more than 15
      previous ultrasound guided cannulations had an increased success rate (95% vs.
      79%, p = 0.01) and increased failure was related to previous catheterization (26%
      vs. 7%, p = 0.02). CONCLUSION: Learning ultrasound guidance for IJV vein
      cannulation was safe and feasible in ICU patients. This process was not
      associated to complications and better results were achieved across the spectrum
      of operator experience.

PMID- 21876921
TI  - Office hysteroscopy study in consecutive miscarriage patients.
AB  - OBJECTIVE: To assess the prevalence of uterine anatomical abnormalities found by
      office diagnostic hysteroscopy in a population of patients experiencing more than
      two consecutive miscarriages and compare the prevalence of uterine abnormalities
      between patients with two miscarriages and those with three or more consecutive
      miscarriages. METHODS: A cross-sectional study of 66 patients with two or more
      consecutive miscarriages diagnosis was conducted. Patients were divided into two
      groups: Group A (up to two miscarriages, 23 patients), and Group B (3
      miscarriages, 43 patients). They underwent an outpatient diagnostic hysteroscopy
      study, with either congenital or acquired abnormalities of the uterine cavity
      being identified. RESULTS: Uterine changes were found in 22 (33.3%) patients,
      with 9 cases of congenital changes [arcuate uterus (4 cases), septate uterus (2
      cases), and bicornuate uterus (1 case)], and 13 patients with acquired changes
      [intrauterine adhesions (7 cases), endometrial polyp (4 cases), and uterine
      leiomyoma (2 cases)]. No significant differences were found between the groups as
      regarding both acquired and congenital uterine changes. A positive correlation
      was found between anatomical changes on hysteroscopy and number of miscarriages
      (r = 0.31; p = 0.02). CONCLUSION: Patients with more than two miscarriages have a
      high prevalence of uterine cavity abnormalities diagnosed by hysteroscopy;
      however there are no differences in prevalence or distribution of these lesions
      related to the number of recurrent miscarriages.

PMID- 21876922
TI  - Maternal mortality profile in Great ABC region from 1997 to 2005.
AB  - OBJECTIVE: To analyze the maternal mortality in the ABC Region, comparing
      indicators from the Committee for the Study of Maternal Mortality in the Great
      ABC Region (CEMM) of the II Regional Health Center of Santo Andre (DIR II), and
      the State Data Analysis System Foundation (SEADE). METHODS: This is a cross
      sectional study. The information was obtained from the database of CEMM DIR II -
      Santo Andre, which includes data from seven counties of the ABC Region. We
      analyzed all deaths of childbearing-age women that occurred from 1997 to 2005 in
      that region. The paired t test, Wilcoxon and Kruskal-Wallis tests were used for
      statistical analysis. RESULTS: There were differences regarding the maternal
      mortality rates in the towns of Diadema, Sao Bernardo do Campo, Santo Andre and
      DIR II, with the coefficients calculated by CEMM being higher than those provided
      by the SEADE (p < 0.001). Concerning the towns of Maua, Rio Grande da Serra,
      Ribeirao Pires and Sao Caetano do Sul, no significant differences were observed
      between these two coefficients (p >= 0.05), although the coefficients provided by
      CEMM were higher than the coefficients obtained from SEADE. CONCLUSION: Our
      results demonstrate that the official data of maternal mortality in Brazil are
      still underestimated and point to the lack of healthcare quality during
      pregnancy, childbirth and postpartum.

PMID- 21876923
TI  - Use of a lactic acid plus lactoserum intimate liquid soap for external hygiene in
      the prevention of bacterial vaginosis recurrence after metronidazole oral
      treatment.
AB  - OBJECTIVE: To determine the recurrence of bacterial vaginosis (BV) after the use
      of a lactic acid plus lactoserum liquid soap starting immediately after the
      treatment with oral metronidazole and the quality of life of the participants.
      METHODS: A total of 123 women with diagnosis of BV with at least three of the
      following criteria: 1) homogeneous vaginal discharge without inflammation of the
      vagina or vulva; 2) vaginal pH >= 4.5; 3) positive Whiff test; and 4) "clue
      cells" in more than 20% of the epithelial cells in the vagina. A Nugent score >=
      4 in the vaginal bacterioscopy was also used. After BV diagnosis, metronidazole
      500 mg was administered orally bid during 7 days. Patients cured of BV were then
      instructed to use 7.5 to 10 mL of a lactic acid plus lactoserum liquid soap once
      a-day for hygiene of the external genital region. Three subsequent control visits
      after starting the hygiene treatment (30, 60, and 90 days; +/- 5 days) were
      scheduled. A questionnaire was applied in the form of visual analogue scale (VAS)
      in all the visits regarding: 1) level of comfort at the genital region; 2)
      malodorous external genitalia; 3) comfort in sexual intercourse; 4) satisfaction
      with intimate hygiene; and 5) self-esteem. RESULTS: Ninety two (74.8%) women
      initiated the use of a lactic acid plus lactoserum liquid soap at visit 1. At
      visit 2, 3, and 4 there were 84, 62 and 42 women available for evaluation,
      respectively. The rate of recurrence of BV was 19.0%, 24.2% and 7.1%,
      respectively in the three visits and vaginal candidiasis was observed in five
      treated women. Quality of life was evaluated in the 42 women who completed the
      four visits schedule and there were significant improvement in the five domains
      assessed. CONCLUSION: A lactic acid plus lactoserum liquid soap for external
      intimate hygiene may be an option for the prevention of BV recurrence after
      treatment and cure with oral metronidazole.

PMID- 21876924
TI  - Antibiotic prescription in a teaching hospital: a brief assessment.
AB  - OBJECTIVE: Antimicrobials are used interchangeably in medical practice,
      contributing to the emergence of resistant microbial strains. METHODS: This study
      describes the antimicrobial audit performed by forecasting analysis of medical
      records of 846 patients at the Hospital Santa Cruz, Santa Cruz do Sul - Rio
      Grande do Sul - Brazil. RESULTS: Of the patients studied, 134 (15.8%) received
      antimicrobials. The audit was conducted interactively, with intervention and
      discussion with the prescriber. Considering the presumptive diagnosis and
      prescribed drug, it was verified that 74.6% of patients on antimicrobials
      received what was considered the first choice treatment. Inadequate antimicrobial
      agent for clinical diagnosis (5.2%) and lack of adjustment for renal function
      (43.7%) were the most frequent errors. CONCLUSION: A strategic plan aimed at the
      rational use of antimicrobials based on educational and interventionist practices
      can help the infection control professional to adjust the routines to improve
      healthcare quality.

PMID- 21876925
TI  - Prevalence and multiplicity of HPV in HIV women in Minas Gerais, Brazil.
AB  - OBJECTIVE: To detect the frequency and subtypes of HPV in the uterine cervix of
      HIV-infected women. METHODS: Sample consisted of 288 HIV-infected women,
      recruited from the public health system of five cities of Minas Gerais, Brazil.
      Women were seen from August 2003 to August 2008. Cervical samples were collected
      for cytological analysis and for HPV DNA detection, using polymerase chain
      reaction (PCR). HPV DNA was classified according to its oncogenic potential in
      low risk (types 6, 11) and high risk (types 16, 18, 31, 33, 35). Colposcopy was
      performed, followed by cervical biopsy when necessary. Categorical variables were
      compared using the Chi-squared test, with a significance level established at the
      5% level. RESULTS: HPV prevalence was 78.8%. Most frequent genotypes were HPV-6
      (63.9%) and HPV-16 (48.5%). High-risk HPV were observed in 70.5% of the women;
      low-risk in 71.4%; both high and low-risk HPV were detected in 55.1% of the
      patients. Multiple HPV genotypes were detected in 64.8% of the patients; two
      genotypes in 23.8%, and three in 18.9%. CONCLUSION: HPV prevalence was high among
      HIV-infected women. Multiple HPV genotypes were common in samples from the
      uterine cervix of HIV-infected women.

PMID- 21876926
TI  - Risk factors for nonmelanoma skin cancer in Taubate, Sao Paulo, Brazil: a case
      control study.
AB  - OBJECTIVE: To identify factors associated with non-melanoma skin cancer in the
      city of Taubate, Sao Paulo, Brazil. METHODS: Hospital-based case-control study
      with individuals residing in Taubate, treated between January 2005 and December
      2006. The subjects were matched 1:1 according to gender and age. Age, gender,
      phototype, European descent, time of residence, sun exposure, time (in years),
      number of hours and time of occupational and non-occupational sun exposure,
      photoprotection, family history and photodamage were independent variables. A
      hierarchical logistic regression was used at three levels. The model adjustment
      was performed using the Hosmer-Lemeshow test and its accuracy was verified by ROC
      curve. The significance level was p < 0.05. RESULTS: There were 132 cases and 132
      controls. Phototype with OR = 3.14 (95% CI 1.79-5.49), hours of occupational 1.76
      (1.04-2.99) and non-occupational sun exposure 1.80 (0.98-3.29) and family history
      2.10 (1.13-3.93) were the variables in the final model. Hosmer-Lemeshow test, p =
      0.97. Accuracy 70% (95% CI 63-76). CONCLUSION: We concluded that fair skin,
      family history and occupational and non-occupational sun exposure were associated
      with non-melanoma skin cancer in Taubate-Sao Paulo.

PMID- 21876928
TI  - Estimated prevalence of childhood end-stage renal disease in the state of Sao
      Paulo.
AB  - OBJECTIVE: To estimate the prevalence of pediatric end-stage renal disease and
      evaluate demographics and renal disease characteristics in state of Sao Paulo
      over the year 2008. METHODS: Observational, descriptive, and cross-sectional
      study based on a population sample with subjects < 18 years. The data collecting
      assumed three forms: 1. A questionnaire for dialysis units; 2. Search in the
      Transplant Center to determine the number and characteristics of patients who had
      been in a transplant waiting list over the study period; 3. Search in the
      database of patients registered at the Latin American Collaborative Registry of
      Pediatric Kidney Transplantation. RESULTS: Data from 301 patients aged 9.0 +/-
      5.8, including 140 girls (46.5%), resulting in an estimate prevalence of 23.4
      cases per million age-related population (pmarp). The age group most frequently
      found was 10 to 15 years (32.2%), and urinary tract malformation was the most
      usual known etiology (24.9%). Most children underwent kidney transplantation
      (62.1%) and among subjects on dialysis, hemodialysis was predominant (71.2%). The
      Sistema Unico de Saude - Unified National Health System - (SUS) provided the
      financial support for treatments. CONCLUSION: The prevalence of 23.4 cases pmarp
      found by the authors is lower than that reported in Western world. We believe
      data were underestimated in the present study, as few dialysis units returned the
      completed questionnaire. This potential bias does not invalidate the exploratory
      character of results. Further mechanisms for retrospective and earlier data
      collecting on pediatric chronic renal disease (CRD) are needed so that the burden
      of this serious health condition can be appropriately sized up.

PMID- 21876927
TI  - Adjuvant radiotherapy in early stage endometrial cancer.
AB  - OBJECTIVE: To compare the rates of overall survival (OS), disease-free survival
      (DFS) and toxicity in different techniques of postoperative radiotherapy for
      stage IA endometrioid adenocarcionoma of endometrium, histological grades 1and 2.
      METHODS: A historical comparison between treatment regimens was performed, and
      133 women with a minimum follow-up of 5 years were included. Teletherapy (TELE
      group), with 22 patients treated from 1988 to 1996, with a 10 MV linear
      accelerator, average dose 46.2 Gy. Low dose rate brachytherapy (LDRB group) was
      performed between 1992 and 1995, in 19 women, with an insertion of Cesium 137, at
      a 60 Gy dose. Fourteen women operated between 1990 and 1996 did not receive
      radiotherapy (NO RT group). High dose rate brachytherapy was performed in 78
      patients (HDRB group), from 1996 to 2004, in five weekly 7 Gy insertions,
      prescribed at 0.5 cm from the vaginal cylinder. RESULTS: The 5-year disease-free
      survival was 94.6% for the HDRB group, 94.1% for the LDRB group, 100% for the
      TELE group and NO RT groups (p = 0.681). The 5-year overall survival was 86.6%
      for the HDRB group, 89.5% for the LDRB group and 90% for the TELE group and NO RT
      groups (p = 0.962). Grades 3-5 late toxicity was 5.3% in LDRB group and 27.3% for
      the TELE group (p < 0.001). CONCLUSION: Patients submitted to adjuvant
      teletherapy showed very high toxicity, which contraindicates that treatment for
      those patients. There may be a role for adjuvant HDRB, but randomized controlled
      trials are still needed to evaluate its benefit.

PMID- 21876929
TI  - Association between different types of physical activities and quality of life in
      women aged 60 years or over.
AB  - OBJECTIVE: To evaluate the association between different types of physical
      activity and quality of life in a sample of women aged 60 or over. SUBJECTS AND
      METHODS: A cross-sectional study was carried out, interviewing 271 women. Of
      these, 141 were recruited in a menopause outpatient clinic and 130 were recruited
      in a social leisure center, in Brazil. The instruments used were the
      International Physical Activity Questionnaire (IPAQ) version 8 and the World
      Health Organization Quality of Life Questionnaire specific for this age group
      (WHOQOL-OLD). Each IPAQ section was evaluated by multiple linear regression
      analysis, considering independent and confounding variables. The significance
      level was set at 5% and the software used was SAS version 9.1.3. RESULTS: The
      mean age of the patients was 67.4 +/- 5.3 years. The mean time devoted to
      physical activity was 2802.7 +/- 1154.9 minutes per week. The total WHOQOL-OLD
      score was 66.9 +/- 11.7. The past, present and future actvities (estimated beta =
      0.021) and, social participation (estimated beta = 0.03) domains had association
      with IPAQ transportation section. The leisure-time domain of the IPAQ had an
      inverse and significant relationship with the quality of life score related to
      present, past and future activities (estimated beta = -0.0269). CONCLUSION:
      Quality of life was negatively influenced by leisure, but time spent in this
      physical activity was the shortest in comparison to other types of physical
      activities. In this sample, only physical activity for transportation was
      positively associated with a better quality of life.

PMID- 21876930
TI  - Environmental factors and endometriosis.
AB  - Endometriosis represents a common gynecological condition affecting 5%-15% of
      childbearing age women and up to 3% 5% of post-menopausal women. This disease is
      defined by the presence of stromal and/or endometrial glandular epithelium
      implants in extra-uterine locations possibly compromising several sites. Humans
      and animals are daily exposed to chemical pollutants that could adversely
      influence physiological processes and potentially cause diseases, including
      endometriosis. In this review, the authors aimed at settling the influence of
      environmental and dietary factors on endometriosis pathogenesis. The mechanism by
      which dioxin and its similes (TCDD/PCBs) act changing the endometrial physiology
      remains uncertain and is speculative due to the difficulty in assessing the
      exposure over intrauterine life, childhood and adulthood and its actual
      consequences, in addition to the limitations to its in vitro reproducibility. We
      need to better understand the mechanism of action of these environmental
      pollutants, not only on reproductive health, but also on overall health of
      individuals and so prevention strategies, including not only population
      education, but setting exposure limits, less polluting techniques and a better
      use of our natural resources, could be promoted.

PMID- 21876931
TI  - Norovirus: an overview.
AB  - Although noroviruses (NoVs) were the first viral agents linked to
      gastrointestinal disease, for a long time they have been considered secondary
      cause of gastroenteritis, second to rotaviruses as etiologic agents. The
      development of molecular techniques in diagnosing NoV provided a clearer insight
      into the epidemiological impact of these viruses, which are currently recognized
      not only as the leading cause of non-bacterial gastroenteritis outbreaks, but
      also as a major cause of sporadic gastroenteritis in both children and adults.
      This review focuses on the required knowledge to understand their morphology,
      genetics, transmission, pathogenesis, and control. Since no vaccine is available,
      prevention of NoV infection relies mainly on strict community and personal
      hygiene measures.

PMID- 21876932
TI  - Early stage breast cancer and radiotherapy: update.
AB  - Breast cancer (BC) is the most common malignancy among women. Therapeutic options
      are based on disease staging, histopathological characteristics, age, and others.
      The objective of the present study is to carry out an update of the concepts and
      definitions of radiotherapy (RT) in conservative treatment of early-stage breast
      cancer, with emphasis on indications, contraindications, RT dose fractionation
      schedules (classic, hypofractionated and partial breast irradiation), adjuvant RT
      in ductal carcinoma in situ (DCIS) and molecular predictors of recurrence.
      MEDLINE, SciELO and Cochrane databases were used for article selection. Adjuvant
      RT is indicated for patients with BC who underwent conservative breast surgery.
      In selected patients, hypofractionated or partial breast irradiation can be used.
      Adjuvant RT should be provided for all patients with DCIS. The correlation of RT
      and molecular predictors of local and systemic recurrence are not yet well-known.

PMID- 21876933
TI  - The locomotor system as seen in Brazilian medical journals: a restricted
      collection of papers.
AB  - This review covers recent publications on the motor system (orthopedics and
      movement) in Brazilian journals recently admitted to the ISI-Thomson Journal of
      Citations Index. Two of these are still pleading for admission into PubMed which
      will eventually enhance their global visibility. We offer this contribution to
      experts on these areas who are regular readers of Revista da Associacao Medica
      Brasileira. Full free copies of all of them are available at www.scielo.br. The
      main areas covered are orthopedics of limb articulations, fractures, movement,
      posture, gait, exercise and animal models.

PMID- 21876935
TI  - Indicators of Ibero-American scientific production.

PMID- 21876936
TI  - Psychometric performance of the brazilian version of the Mini-cuestionario de
      calidad de vida en la hipertension arterial (MINICHAL).
AB  - This study aimed to evaluate the feasibility, acceptability, ceiling and floor
      effects, reliability, and convergent construct validity of the Brazilian version
      of the Mini Cuestionario de Calidad de Vida en la Hipertension Arterial
      (MINICHAL). The study included 200 hypertensive outpatients in a university
      hospital and a primary healthcare unit. The MINICHAL was applied in 3.0 (+/- 1.0)
      minutes with 100% of the items answered. A "ceiling effect" was observed in both
      dimensions and in the total score, as well as evidence of measurement stability
      (ICC=0.74). The convergent validity was confirmed by significant positive
      correlations between similar dimensions of the MINICHAL and the SF-36, and
      significant negative correlations with the Minnesota Living with Heart Failure
      Questionnaire - MLHFQ, however, correlations between dissimilar constructs were
      also observed. It was concluded that the Brazilian version of the MINICHAL
      presents evidence of reliability and validity when applied to hypertensive
      outpatients.

PMID- 21876937
TI  - Health related quality of life of patients undergoing oral anticoagulation
      therapy.
AB  - This is a descriptive cross-sectional study, which aimed to analyze the health
      related quality of life (HRQoL) and its relationship with gender, age, duration
      and indication for the use of oral anticoagulants. A total of 178 patients were
      interviewed and the HRQoL was assessed through eight domains of the SF-36. The
      descriptive statistics used were, the Student's t, ANOVA and Tukey's tests for
      the comparison of the means between the groups. The indication for use was
      predominantly the metallic prosthetic heart valve (50%) with warfarin the most
      widely prescribed anticoagulant (83.3%). The means of the domains of the SF-36
      ranged from 82 (Social aspects) to 54.8 (Physical aspects). Women, elderly,
      patients diagnosed with atrial fibrillation and with less than one year of
      medication use, presented a worse HRQoL evaluation. The results obtained can
      guide nursing actions, in that they indicate possible associations between the
      HRQoL and the sociodemographic and clinical variables of the patients.

PMID- 21876938
TI  - Symptoms of depression and quality of life of people living with HIV/AIDS.
AB  - This is a cross-sectional study conducted with 228 people living with HIV/AIDS in
      a municipality in the State of Sao Paulo during 2007 and 2008. The aims of this
      study were to investigate the intensity of the depressive symptoms in individuals
      with HIV/AIDS treated at two referral units in Ribeirao Preto, Brazil, and to
      compare the quality of life with the different degrees of intensity of the
      depressive symptoms in these individuals, according to gender. Data were
      collected through individual interviews, using the Beck Depression Inventory and
      HIV/AIDS Targeted Quality of Life (HATQoL). A total of 63 (27.6%) patients with
      symptoms of depression (mild, moderate and severe) were detected. The women
      presented more severe symptoms of intensity of depression than men. Individuals
      with depressive symptoms presented lower scores of quality of life than
      individuals without these symptoms, with statistically significant differences
      between the means/medians in most domains of the HATQoL. Healthcare professionals
      should offer integral care for people with HIV/AIDS, emphasizing the depressive
      symptoms.

PMID- 21876939
TI  - Content validity of the short version of the subscale of the State-Trait Anxiety
      Inventory (STAI).
AB  - The goal was to describe the content validity of a short version of the state
      subscale of Spielberger's "State-Trait Anxiety Inventory (STAI)", based on the
      original version adapted to Spanish, in Spanish patients receiving invasive
      mechanical ventilation (IMV). The sample consisted of 16 patients receiving IMV
      at the Alicante Hospital (Spain), who selected the items from the full Spanish
      version of the STAI-state that were most relevant to them. Items 1, 5, 9, 10, 12
      and 20 from the original scale are the most relevant for the Spanish patients
      receiving IMV and 5 of these are included in the short version of the scale
      (83.3% agreement). The short scale has shown adequate content validity for
      Spanish patients receiving IMV.

PMID- 21876940
TI  - Explanatory digital video disc with patients undergoing diagnostic cardiac
      catheterization.
AB  - The aim of this study was to evaluate knowledge of patients before outpatient
      diagnostic cardiac catheterization after viewing an explanatory Digital Video
      Disc, in a cardiology reference hospital. This cross-sectional study was carried
      out with patients undergoing their first cardiac catheterization and was
      performed from May to June 2009 in the hemodynamic sector. An instrument was used
      with questions (12) regarding the patients' understanding of the procedure. The
      intervention was a five-minute video prepared by the researchers. The sample was
      composed of 94 patients, divided into an intervention group (45) and a control
      group (49), with a mean age of 55 +/- 9 years and predominantly male. The
      patients of the IG had a higher rate of correct answers (74.6 +/- 17.1) compared
      to the CG (31.6 +/- 18.8), P=.000. The results demonstrated the efficacy of the
      presentation of a guidance video for patients undergoing a hemodynamic procedure.

PMID- 21876941
TI  - Evaluation of the virtual learning object "Diagnostic reasoning in nursing
      applied to preterm newborns".
AB  - The potential use of computer technology in teaching and continuous education for
      nursing motivated the development of this study to evaluate the virtual learning
      object, "Diagnostic Reasoning in Nursing Applied to Preterm Newborns" at an
      intermediate neonatal care unit. This descriptive study evaluates the appearance
      and content of the virtual object concerning aspects related to presentation,
      organization, usability and overall impression. Experts from the fields of
      computer technology (12) and nursing (31) participated in the evaluation process.
      Each sub-item of the instrument was assessed on a Likert scale and blank space
      was provided for comments/suggestions. All items were positively evaluated by
      over 80% of the experts, except for the 'informational density' criterion in the
      evaluation performed by computer technology experts. The developed product is
      considered adequate to be used for teaching for nursing students and in
      continuous education of diagnostic reasoning in the development of Nursing
      Diagnoses for preterm newborns, in the problem-posing pedagogical framework.

PMID- 21876942
TI  - Efficacy of different instruments for the identification of the nursing diagnosis
      spiritual distress.
AB  - The study aims to identify the nursing diagnosis Spiritual distress in 120
      patients with Chronic Renal Insufficiency, using different instruments, and to
      evaluate the effectiveness of these instruments in support of this
      identification. Data were collected separately by two nurses using a
      questionnaire containing sociodemographic information and the defining
      characteristics of Spiritual distress, as well as direct questioning to the
      patient regarding the presence of the diagnosis and the instruments: the
      Spirituality Rating Scale; Pinto and Pais-Ribeiro's Spirituality Scale; and the
      Spiritual Well-being Scale. The study found that 25.8% to 35.8% of the patients
      had the diagnosis. The diagnostic evaluation developed by the expert nurses
      presented no divergence between the two and obtained a perfect concordance
      coefficient (96.7%) with the opinion of the patient; this demonstrated
      substantial concordance with the Existential Well-being Sub-scale (83.3%) and
      with the Pinto e Pais-Ribeiro's Spirituality Scale (87.5%), which demonstrated
      their usefulness for diagnostic identification.

PMID- 21876943
TI  - Factors associated with death and readmission into the Intensive Care Unit.
AB  - This study identifies the factors associated with death and readmission into the
      Intensive Care Unit. This is a longitudinal prospective study of 600 adult
      patients admitted in general Intensive Care Units of four hospitals in Sao Paulo,
      Brazil. The multiple regression analysis showed that patients with a longer
      length of stay and higher Nursing Activities Score, Simplified Acute Physiology
      Score II and Logistic Organ Dysfunction Score on the last day in the unit had a
      higher chance of death. Nevertheless, higher Nursing Activities Score and
      Logistic Organ Dysfunction Score on the first day in the intensive care unit were
      protective factors against death. Viral hepatitis as an antecedent increased the
      chance of readmission. On the other hand, higher Nursing Activities Score at
      discharge decreased this risk. It was concluded that the nursing workload was the
      main variable related to the outcomes analyzed.

PMID- 21876944
TI  - Sleep problems and social support: Frailty in a Brazilian Elderly Multicenter
      study.
AB  - This study identifies relationships among the quality of perceived social support
      and sleep problems and napping habits in community-dwelling elderly. This study
      is part of a larger multicenter project entitled "Frailty in Brazilian Elderly
      Individuals", conducted in 17 Brazilian cities. A total of 498 elderly
      individuals capable of participating in interviews and free of cognitive deficits
      or functional impairment were found. The following instruments were used in data
      collection: Questionnaire addressing socio-demographic data; Interpersonal
      Support Evaluation Scale; questions concerning sleep patterns (Nottingham Health
      Profile); questions related to napping habits (Minnesota Leisure Activity
      Questionnaire). Descriptive statistics and the Mann-Whitney test were used for
      data analysis. The elderly individuals who reported having sleep problems in
      general, taking longer to fall asleep and sleeping poorly at night had lower
      scores on the Interpersonal Support Evaluation Scale than the elderly who denied
      such problems. Strategies to improve the quality of social support could also
      help reduce sleep problems.

PMID- 21876945
TI  - Identification and mapping of the nursing diagnoses and actions in an Intensive
      Care Unit.
AB  - This is a descriptive study with the aim of examining the nursing diagnoses
      labels and actions prescribed by nurses in the clinical records of patients
      hospitalized in an Adult Intensive Care Unit. A sample of 44 clinical records was
      obtained and a total of 1087 nursing diagnoses and 2260 nursing actions were
      identified. After exclusion of repetitions 28 different nursing diagnoses labels
      and 124 different nursing actions were found. Twenty-five nursing diagnoses
      labels were related to human psychobiological needs and three to psychosocial
      needs. All the nursing actions were mapped to the physiological needs and also to
      interventions of the Nursing Interventions Classification-NIC. Concordance of
      100% was obtained between the experts in the validation process of the mapping
      performed, both for the nursing diagnoses labels and actions. Similar studies
      should be conducted for the identification and development of nursing diagnoses
      and actions.

PMID- 21876946
TI  - Nursing diagnosis: educational strategy based on problem-based learning.
AB  - This study aimed to evaluate the effectiveness of a teaching strategy on nursing
      diagnoses based on problem-based learning in the performance of clinical
      reasoning and diagnostic trial of undergraduate students. Experimental study
      conducted in two phases: content validation of problems and implementation of
      educational strategy. The results showed improvement in the data pooling ability
      of students in the experimental group. It is concluded that the strategy put in
      practice exerted a positive influence.

PMID- 21876947
TI  - Medication therapy: adherence, knowledge and difficulties of elderly people from
      bipolar disorder.
AB  - This study aimed to verify the adherence, knowledge and the difficulties of
      elderly patients with Bipolar Affective Disorder (BAD) in relation to the
      prescribed pharmacological therapy for the control of this disorder. The study
      included 17 elderly patients with BAD treated at a Mental Health Center. Semi
      structured interviews were conducted and scales were applied. The data were
      analyzed using a quali-quantitative approach. A low level of adherence to the
      pharmacological treatment and a deficit in knowledge in relation to the
      medication were identified, especially regarding the dose and frequency of
      administration. Among the difficulties inherent to the pharmacotherapy, the
      obligation of polypharmacotherapy, the desire to quit the pharmacological
      treatment, limitations in the self-administration of the medication, collateral
      effects, and doubts about the need for the medication were related. Investment is
      needed in educational activities and in the promotion of adherence that address
      the difficulties experienced by elderly people with BAD in the following of the
      pharmacotherapy in order to ensure safety in the medication therapy.

PMID- 21876948
TI  - Factors that hinder of integrality in dialysis care.
AB  - This study analyzes the factors, which from the perspective of the health team
      and users, hinder the implementation of integrality in care provided by a
      dialysis facility. This qualitative study collected data through semi-structured
      interviews held with 16 health professionals and eight users from a university
      hospital in Rio Grande do Sul, Brazil. Data were analyzed through thematic
      content analysis. Among the factors that hinder the implementation of integrality
      in hemodialysis care, the following were highlighted: a deficient service
      network, delay in accessing diagnostic exams and consultations with specialists,
      and a reduced number of professionals in the support team. The conclusion is that
      the health services network needs to be expanded and an effective interface
      between such networks and dialysis services needs to be established in order to
      overcome the reported difficulties and contribute to the implementation of
      integrality in dialysis care.

PMID- 21876949
TI  - Drug interactions of anti-microbial agents used in hematopoietic stem cell
      transplantation.
AB  - This study analyzed potential drug interactions (PDIs) of antimicrobials used in
      patients of hematopoietic stem cell transplantation and identified associated
      factors. The sample consisted of 70 patients admitted to a hospital in Sao Paulo.
      The PDIs were analyzed through the consultation of the Drug Interactions Facts
      and Drug Interactions Handbook. Descriptive statistics and logistic regression
      were used. Half of the sample was exposed to 13 PDIs, which occurred with
      fluconazole (53.8%), ciprofloxacin (30.8%) and sulfamethoxazole-trimethoprim
      (15.4%). Most (92.3%) were of moderate severity, with good evidence (61.6%),
      early delayed effect (61.5%) and need to have their therapy monitored (76.9%).
      Patients with four or more medications (p<0.001), aged between 40-49 years of age
      (p <0.001), and being male (p<0.001) were associated with PDIs. A PDI may result
      in adverse outcomes, impacting patients' morbidity and mortality. Combination
      regimens can be safe, provided there is careful monitoring by professionals
      involved in care delivery.

PMID- 21876950
TI  - The experience of thalassemic adults with their treatment.
AB  - This study, based on medical anthropology and oral reports, analyzes the meanings
      attributed by thalassemic adults to their experiences with the treatment.
      Interviews were used to collect data, which were analyzed through inductive
      thematic analysis. Eleven young adults, six of whom were men, at different ages,
      with different educational levels and occupations participated in the study. The
      meanings are discussed through the theme "the lives of patients with thalassemia
      in relation to their treatment". This core meaning highlights the difference made
      in their identity by having the disease trait, the recognition of the importance
      of adhering to their treatment, the difficulties in maintaining their social
      functions, the patients' irregular treatment adherence and their justifications
      for non-adherence to their treatment. Thalassemic patients conform to their
      condition and employ a normalization strategy to control the disease and justify
      irregular treatment adherence.

PMID- 21876951
TI  - Trends in infant mortality rate and mortality for neonates born at less than 32
      weeks and with very low birth weight.
AB  - The aim of the study was to assess the trend of the infant mortality rate between
      1990-2004 and the neonatal mortality between 2000-2005 in infants born at less
      than 32 weeks of gestational age or with very low birth-weight. Based on
      secondary data, infant mortality rate and by its component for Valdivia city were
      compared with national indicators. Mortality at <32 weeks and <1500g was
      calculated, establishing causes of death and evaluating its relation with
      specific interventions, such as the use of surfactant and antenatal corticoids.
      Since the year 2000, infant mortality rates have stopped their decrease in
      comparison to the preceding decade and the gap between national and local rates
      before 2000 was drastically reduced. Mortality at <32 weeks and <1500g varied
      between 88% and 200% of liveborns, emphasizing respiratory distress as the main
      cause of death. The use of corticoids and surfactant was in line with reductions
      in mortality rates.

PMID- 21876952
TI  - Independence of children with Down syndrome: the experiences of families.
AB  - This study develops a theoretical model concerning the experience of families of
      children with Down syndrome in preschool and school age. The frameworks used were
      Symbolic Interactionism and Grounded Theory. Semi-structured interviews were used
      as the instrument of investigation and ten families participated in the study.
      The Theoretical Model "Seeking the child's independence and autonomy through
      constant stimulation" was identified, which shows the family's efforts to enable
      the child to develop the best s/he can through stimulation in order to become
      less dependent in the future. This model can be used to facilitate interaction
      with the family and can be further expanded. Nurses should use spaces dedicated
      to care delivery to establish bonds with the family, and seek other spaces
      families frequent, to better meet their needs, since there are significant gaps
      in care and research addressing this population. Instead, they should be welcomed
      and seen as a partner in care delivery.

PMID- 21876953
TI  - Accessibility to tuberculosis treatment: assessment of health service
      performance.
AB  - The aim of this study was to assess the accessibility of patients to the
      treatment of tuberculosis in Ribeirao Preto, countryside of Sao Paulo State.
      Evaluation study type, with a quantity approach. Interviews with 100 patients
      initiated on anti-tuberculosis chemotherapy between 2006-2007 were conducted,
      using a structured questionnaire based on the Primary Care Assessment Tool
      (PCAT). Data were analyzed through variance analysis. There was a positive
      feedback regarding to organizational accessibility, however, the performance of
      health services has been unsatisfactory in providing transportation vouchers and
      in addressing the need to use transport for displacement to the health unit,
      resulting in indirect costs to patients. The services with the highest number of
      patients treated were those with higher irregularity in the conduct of home
      visits, showing that the availability of resources (human, material and time) and
      the organization of care may influence the accessibility to treatment.

PMID- 21876955
TI  - Estimating the nursing staff required in a new hospital.
AB  - Opening a new hospital poses a complex and consequential set of challenges. One
      of these challenges is to estimate the nursing staff. The aim of this article is
      to report the entire process adopted to estimate the required nursing staff for a
      new Hospital in Brazil. The nursing staff was projected according to the
      Brazilian Federal Nursing Council (Cofen). We applied an equation to estimate
      nursing staff and compared the results with two other existing hospitals. A
      significant difference (p<0.05) was observed when comparing the Nurse-License
      Practice Nurse ratio recommended by Cofen between the new Hospital and other
      hospitals. This statistical difference is mostly due to reduced nurse staff in
      intensive care units. Almost one year after the hospital opened its doors, it is
      necessary to review nursing staff hours with the real information to reinforce
      the expenditure on these personnel and to evaluate the decisions made so far.

PMID- 21876954
TI  - Collective and decentralized management model in public hospitals: perspective of
      the nursing team.
AB  - This research aims to present the implementation of the collective and
      decentralized management model in functional units of a public hospital in the
      city of Ribeirao Preto, state of Sao Paulo, according to the view of the nursing
      staff and the health technical assistant. This historical and organizational case
      study used qualitative thematic content analysis proposed by Bardin for data
      analysis. The institution started the decentralization of its administrative
      structure in 1999, through collective management, which permitted several
      internal improvements, with positive repercussion for the care delivered to
      users. The top-down implementation of the process seems to have jeopardized
      workers adherence, although collective management has intensified communication
      and the sharing of power and decision. The study shows that there is still much
      work to be done to concretize this innovative management proposal, despite the
      advances regarding the quality of care.

PMID- 21876956
TI  - Living and working conditions of the professionals of the a Mobile Emergency
      Service.
AB  - The assistance provided by the Mobile Emergency Service (SAMU) may result in
      changes in the health of the workers. This is a cross-sectional epidemiological
      study which aimed to evaluate the sociodemographic, health and lifestyle
      characteristics and the working conditions among professionals of the SAMU in
      Campinas, SP, Brazil. A questionnaire was used to collect sociodemographic,
      lifestyle, health and work data. The sample consisted of 197 workers - nurses,
      physicians, nursing technicians, auxiliary nurses, drivers and administrative
      personnel. There was a prevalence of males (61.4%), mean age 39.1 years (SD=8.3);
      married (63.5%), with children (76.7%); of the category of drivers (30.5%),
      monitored by physicians (18.3%) and auxiliary nurses (16.8%); 42.1% had
      additional employment, 48% performed overtime and 25.3% worked more than 70 hours
      per week. The majority practiced physical (56.5%) and leisure (96.5%) activities.
      New facets of the life of these workers were revealed and may contribute to
      programs aimed at health promotion.

PMID- 21876957
TI  - Stressors in nurses working in intensive care units.
AB  - This is a descriptive cross-sectional study. The sample consisted of 235 nurses
      from two intensive care units in Porto (Portugal). The purpose of this study was
      to identify stressors for nurses working in intensive care units. The data was
      collected using the following: i) a questionnaire (for socio-demographic
      variables, physical aspects of work and variables related to the work context;
      ii) Interpersonal Work Relations Scale; iii) Nurse Stress Index. Nurses in the
      early phase of their career have higher stress levels (X = 81). An inadequate
      physical work structure leads to higher stress levels (X = 83). The worse the
      interpersonal relations are, the higher stress levels nurses feel (Spearman
      correlation coefficient =-0.331). Nurses who have a bad relationship with their
      work superiors view the dimension "Support and Organizational Involvement" as a
      stressor (Student's t test, p<0.001).

PMID- 21876958
TI  - Methods for nurses to measure body composition.
AB  - Among the methods available for assessing body composition, traditional methods
      like hydrodensitometry and skin-fold measurements are well known. In this review,
      we focus on the impedance and interactance methods, which use systems that are
      usually inexpensive, easily transportable and simple to operate. We also discuss
      the usefulness of dual energy X-ray absorptiometry, particularly for the
      measurement of fat distribution. Nurses need to be skilled in the use of the
      equipment and familiar with the techniques.

PMID- 21876959
TI  - Changes in the care context: challenges for nursing.
AB  - This research aimed to identify global changes in the way of practicing and
      understanding care, as well as the demands population change has generated and
      the implications for family and professional caregivers. An integrative
      literature review was performed, identifying 284 papers with the following
      descriptors: care and caregivers, associated with the descriptor "Nursing",
      published between 2005 and 2010. Forty-one papers were selected that correspond
      to the intended goal. The results point towards a care transition model,
      reconfigured by new care demands, which are mainly associated with the increase
      in chronic conditions and population aging. In addition, the change in social and
      individual roles takes care beyond the family sphere and closer to shared social
      responsibility. Care is the axis around which nurses rotate. Hence, it is
      fundamental to analyze this context, which demands evolution in professional care
      development.

PMID- 21876960
TI  - Job satisfaction of nursing staff: integrative review.
AB  - Job satisfaction consists of a feeling of wellbeing, resulting from the
      interaction of several occupational aspects, and may influence the worker's
      relationship with the organization, clients and family. Hence, it becomes
      important for the quality of nursing care to reflect on this topic in depth.
      Therefore, this study aimed to examine the scientific evidence related to job
      satisfaction in Brazilian nursing. An integrative literature review was carried
      out in the databases LILACS, MEDLINE, BDENF and Cochrane Library, totaling 17
      publications, categorized in: Job Satisfaction, Job Dissatisfaction and
      Associated Factors. It was concluded that job satisfaction is determined by a
      complex network of factors and may vary depending on the group studied.
      Additional research, particularly of evidence level III in different nursing
      fields, covering all of Brazil, is necessary to support the implementation of
      occupational improvements.

PMID- 21876962
TI  - Public awareness of testicular cancer and testicular self-examination in academic
      environments: a lost opportunity.
AB  - BACKGROUND: Although testicular cancer is the most common cancer among 18- to 50
      year-old males, healthcare providers seldom teach testicular self-examination
      techniques to clients, thus potentially missing opportunities for early
      detection. This form of cancer is easily diagnosable by testicular self
      examination and is 96% curable if detected early. Periodic self-examination must
      be performed for early detection. Knowledge deficits and sociocultural norms
      contribute to low levels of health-related knowledge in most patients, resulting
      in undue delays before seeking medical advice. OBJECTIVE: Our aim is to assess
      the level of awareness of testicular cancer and the prevalence of the practice of
      testicular self-examination in academic environments to enable appropriate
      interventions. METHOD: A cross-sectional survey was administered to 750
      consecutive males aged 18-50 years in three tertiary institutions in Port
      Harcourt from October 2008 to April 2009. RESULT: Knowledge or awareness of
      testicular cancer was poor. Almost all of the respondents were unaware that
      testicular lumps may be signs of cancer. A lump was typically construed as a
      benign carbuncle or something that could resolve spontaneously. The main factor
      contributing to respondents' lack of knowledge of testicular cancer was that few
      reported that they were "ever taught about testicular self-examination."
      CONCLUSION: Young adult men are unaware of their risk for testicular cancer,
      which is the most common neoplasm in this age group. Healthcare providers are not
      informing them of this risk, nor are they teaching them the simple early
      detection technique of self-examination of the testes.

PMID- 21876963
TI  - Reduced plasma adiponectin levels relative to oxidized low density lipoprotein
      and nitric oxide in coronary artery disease patients.
AB  - INTRODUCTION: Adiponectin is a circulating hormone that is produced exclusively
      by adipocytes and has antiinflammatory and anti-atherogenic properties. The
      hypothesis that there are differences in adiponectin levels between stable and
      unstable coronary-artery disease patients remains controversial. Furthermore, the
      potential relationships between the plasma adiponectin level and the inflammatory
      and non-inflammatory markers (oxidized low density lipoprotein and nitric oxide)
      in patients with stable and unstable coronary-artery disease relative to normal
      subjects have not been assessed. OBJECTIVES: To assess whether plasma adiponectin
      levels differ among patients with stable and unstable coronary-artery disease and
      among control subjects, and to correlate plasma adiponectin level with
      inflammatory and clinical risk factors (such as oxidized-LDL and nitric oxide) in
      these patients. METHODS: This study included 50 control subjects, 50 stable
      angina patients and 50 unstable angina patients with angiographically documented
      coronary-artery disease. Plasma adiponectin and oxidized-LDL levels were
      determined using an enzyme immunoassay. Plasma nitric oxide, high sensitivity C
      reactive protein and lipid profile levels were also measured. RESULTS: Plasma
      adiponectin levels were lower in the unstable angina patients (4.9 +/- 1.30
      ug/mL) than in the stable angina patients (6.34 +/- 1.0 ug/mL) or in the controls
      (9.25 +/- 1.8 ug/mL); these levels were also significantly lower in stable angina
      patients versus controls (p<0.001). Plasma adiponectin levels were negatively
      correlated with oxidized-LDL, high sensitivity C-reactive protein, lipid profile
      and other clinical risk factors but positively correlated with nitric oxide.
      CONCLUSION: Plasma adiponectin levels were found to be lower in both stable and
      unstable angina patients relative to control subjects, and the correlation
      between plasma adiponectin and cardiovascular markers is weakened in these
      patients.

PMID- 21876964
TI  - Different ventilatory responses to progressive maximal exercise test performed
      with either the arms or legs.
AB  - OBJECTIVE: This study aimed to compare respiratory responses, focusing on the
      time-domain variability of ventilatory components during progressive
      cardiopulmonary exercise tests performed on cycle or arm ergometers. METHODS: The
      cardiopulmonary exercise tests were conducted on twelve healthy volunteers on
      either a cycle ergometer or an arm ergometer following a ramp protocol. The time
      domain variabilities (the standard deviations and root mean squares of the
      successive differences) of the minute ventilation, tidal volume and respiratory
      rate were calculated and normalized to the number of breaths. RESULTS: There were
      no significant differences in the timing of breathing throughout the exercise
      when the cycle and arm ergometer measurements were compared. However, the arm
      exercise time-domain variabilities for the minute ventilation, tidal volume and
      respiratory rate were significantly greater than the equivalent values obtained
      during leg exercise. CONCLUSION: Although the type of exercise does not influence
      the timing of breathing when dynamic arm and leg exercises are compared, it does
      influence time-domain ventilatory variability of young, healthy individuals. The
      mechanisms that influence ventilatory variability during exercise remain to be
      studied.

PMID- 21876965
TI  - Tgf-beta1 expression as a biomarker of poor prognosis in prostate cancer.
AB  - OBJECTIVE: To evaluate the correlation between transforming growth factor beta
      (TGF-beta1) expression and prognosis in prostate cancer. PATIENTS AND METHODS:
      TGF-beta1 expression levels were analyzed using the quantitative real-time
      polymerase chain reaction to amplify RNA that had been isolated from fresh-frozen
      malignant and benign tissue specimens collected from 89 patients who had
      clinically localized prostate cancer and had been treated with radical
      prostatectomy. The control group consisted of li patients with benign prostate
      hyperplasia. The expression levels of TGF-beta1 were compared between the groups
      in terms of Gleason scores, pathological staging, and prostate-specific antigen
      serum levels. RESULTS: In the majority of the tumor samples, TGF-beta1 was
      underexpressed 67.0% of PCa patients. The same expression pattern was identified
      in benign tissues of patients with prostate cancer. Although most cases exhibited
      underexpression of TGF-beta1, a higher expression level was found in patients
      with Gleason scores >= 7 when compared to patients with Gleason scores < 7(p =
      0.002). Among the 26 cases of TGF-beta1 overexpression, 92.3% had poor prognostic
      features. CONCLUSIONS: TGF-beta1 was underexpressed in prostate cancers; however,
      higher expression was observed in tumors with higher Gleason scores, which
      suggests that TGF-beta1 expression may be a useful prognostic marker for prostate
      cancer. Further studies of clinical specimens are needed to clarify the role of
      TGF-beta1 in prostate carcinogenesis.

PMID- 21876966
TI  - Factors associated with medicine use and self medication are different in
      adolescents.
AB  - OBJECTIVE: To estimate the prevalence of medicine use among high school students
      (14-18 years old) living in an urban area in Southern Brazil and the proportion
      who self-medicate and to explore the association between medicine use and
      demographic, socioeconomic, and behavioral variables. METHODS: A school-based
      survey was conducted among high school students in the city of Maringa/PR, Brazil
      in 2007. The sample students were selected through two-stage random sampling. The
      sample included 991 students (54.5% females) from eight public and four private
      high schools. The data were collected using a structured questionnaire. Only
      medications used within the 15 days preceding data collection were considered.
      The independent variables studied were sex, age, socioeconomic status, living
      with parents, employment status, smoking habits, and alcohol use. RESULTS: The
      prevalence of medicine use among the adolescents was 55.8% (females = 64.3%,
      males = 45.7%, p<0.001) and 52.6% of this use represented self medication
      (females = 51.0%, males = 56.8, p = 0.21). The factors associated with medicine
      use were age, employment, and smoking, while the factors associated with self
      medication were male gender and employment. Chronic users did not tend to self
      medicate. CONCLUSION: The data from this study demonstrate a high prevalence of
      medicine use and self medication; however, the variables associated with medicine
      use and self medication differed. Urgent strategies to promote the rational use
      of drugs in this population and their families are necessary.

PMID- 21876967
TI  - A sigmoidal fit for pressure-volume curves of idiopathic pulmonary fibrosis
      patients on mechanical ventilation: clinical implications.
AB  - OBJECTIVE: Respiratory pressure-volume curves fitted to exponential equations
      have been used to assess disease severity and prognosis in spontaneously
      breathing patients with idiopathic pulmonary fibrosis. Sigmoidal equations have
      been used to fit pressure-volume curves for mechanically ventilated patients but
      not for idiopathic pulmonary fibrosis patients. We compared a sigmoidal model and
      an exponential model to fit pressure-volume curves from mechanically ventilated
      patients with idiopathic pulmonary fibrosis. METHODS: Six idiopathic pulmonary
      fibrosis patients and five controls underwent inflation pressure-volume curves
      using the constant-flow technique during general anesthesia prior to open lung
      biopsy or thymectomy. We identified the lower and upper inflection points and fit
      the curves with an exponential equation, V = A-B.e-k.P, and a sigmoid equation, V
      = a+b/(1+e-(P-c)/d). RESULTS: The mean lower inflection point for idiopathic
      pulmonary fibrosis patients was significantly higher (10.5 +/- 5.7 cm H2O) than
      that of controls (3.6 +/- 2.4 cm H2O). The sigmoidal equation fit the pressure
      volume curves of the fibrotic and control patients well, but the exponential
      equation fit the data well only when points below 50% of the inspiratory capacity
      were excluded. CONCLUSION: The elevated lower inflection point and the sigmoidal
      shape of the pressure-volume curves suggest that respiratory system compliance is
      decreased close to end-expiratory lung volume in idiopathic pulmonary fibrosis
      patients under general anesthesia and mechanical ventilation. The sigmoidal fit
      was superior to the exponential fit for inflation pressure-volume curves of
      anesthetized patients with idiopathic pulmonary fibrosis and could be useful for
      guiding mechanical ventilation during general anesthesia in this condition.

PMID- 21876968
TI  - Respiratory exercise program for elderly individuals with asthma.
AB  - INTRODUCTION: Asthma in older adults is frequently underdiagnosed, as reflected
      by approximately 60% of asthma deaths occurring in people older than age 65.
      OBJECTIVE: The present study evaluates the effects of a respiratory exercise
      program tailored for elderly individuals with asthma. We are not aware of any
      other reports examining breathing exercises in this population. METHODS: Fourteen
      patients concluded the 16-week respiratory exercise program. All the patients
      were evaluated with regard to lung function, respiratory muscle strength, aerobic
      capacity, quality of life and clinical presentation. RESULTS: After 16 weeks of
      this open-trial intervention, significant increases in maximum inspiratory
      pressure and maximum expiratory pressure (27.6% and 20.54%, respectively) were
      demonstrated. Considerable improvement in quality of life was also observed. The
      clinical evaluations and daily recorded-symptoms diary also indicated significant
      improvements and fewer respiratory symptoms. A month after the exercises were
      discontinued, however, detraining was observed. DISCUSSION: In conclusion, a
      respiratory exercise program increased muscle strength and was associated with a
      positive effect on patient health and quality of life. Therefore, a respiratory
      training program could be included in the therapeutic approach in older adults
      with asthma.

PMID- 21876969
TI  - Intestinal microsporidiosis: a hidden risk in rheumatic disease patients
      undergoing anti-tumor necrosis factor therapy combined with disease-modifying
      anti-rheumatic drugs?
AB  - OBJECTIVE: Immunosuppressed patients are at risk of microsporidiosis, and this
      parasitosis has an increased rate of dissemination in this population. Our
      objective was to evaluate the presence of microsporidiosis and other intestinal
      parasites in rheumatic disease patients undergoing anti-tumor necrosis
      factor/disease-modifying anti-rheumatic drug treatment. METHODS: Ninety-eight
      patients (47 with rheumatoid arthritis, 31 with ankylosing spondylitis and 11
      with psoriatic arthritis) and 92 healthy control patients were enrolled in the
      study. Three stool samples and cultures were collected from each subject.
      RESULTS: The frequency of microsporidia was significantly higher in rheumatic
      disease patients than in control subjects (36 vs. 4%, respectively; p<0.0001), as
      well as in those with rheumatic diseases (32 vs. 4%, respectively; p<0.0001),
      ankylosing spondylitis (45 vs. 4%, respectively; p<0.0001) and psoriatic
      arthritis (40 vs. 4%, respectively; p<0.0001), despite a similar social-economic
      class distribution in both the patient and control groups (p = 0.1153). Of note,
      concomitant fecal leukocytes were observed in the majority of the microsporidia
      positive patients (79.5%). Approximately 80% of the patients had gastrointestinal
      symptoms, such as diarrhea (26%), abdominal pain (31%) and weight loss (5%),
      although the frequencies of these symptoms were comparable in patients with and
      without this infection (p>0.05). Rheumatoid arthritis, ankylosing spondylitis and
      psoriatic arthritis disease activity parameters were comparable in both groups
      (p>0.05). The duration of anti-tumor necrosis factor/disease-modifying anti
      rheumatic drugs and glucocorticoid use were also similar in both groups.
      CONCLUSION: We have documented that microsporidiosis with intestinal mucosa
      disruption is frequent in patients undergoing concomitant anti-tumor necrosis
      factor/disease-modifying anti-rheumatic drug therapy. Impaired host defenses due
      to the combination of the underlying disease and the immunosuppressive therapy is
      the most likely explanation for this finding, and this increased susceptibility
      reinforces the need for the investigation of microsporidia and implementation of
      treatment strategies in this population.

PMID- 21876970
TI  - Risk of herpes zoster in patients with systemic lupus erythematosus: a three-year
      follow-up study using a nationwide population-based cohort.
AB  - OBJECTIVE: The goal of the present study was to estimate the risk ratio of herpes
      zoster among systemic lupus erythematosus patients after disease onset compared
      with a cohort of patients without systemic lupus erythematosus over a three-year
      period. METHODS: A nationwide population-based cohort study using the National
      Health Insurance Research Database identified 10,337 new cases of systemic lupus
      erythematosus as the study cohort. In addition, 62,022 patients without systemic
      lupus erythematosus, who were matched for age, gender, and date of systemic lupus
      erythematosus diagnosis, were used as the comparison cohort. These cohorts were
      followed-up for three years. A Cox proportional hazard regression was performed
      to estimate the risk ratio of herpes zoster, with adjustments for age, gender,
      level of insurance, urbanization level, geographic region, comorbid medical
      conditions, average daily dosage of corticosteroids, and the use of immune
      modulation agents. RESULTS: Compared to patients without systemic lupus
      erythematosus, the crude risk ratio and adjusted risk ratio of herpes zoster
      among systemic lupus erythematosus patients were 7.37 (95% confidence interval
      6.75-8.04) and 2.45 (95% confidence interval 1.77-3.40), respectively. Stratified
      by gender, the adjusted risk ratio of herpes zoster was 2.10 (95% confidence
      interval 1.45-2.99) in women and 7.51 (95% confidence interval 2.89-19.52) in
      men. Stratified by age, the adjusted risk ratio peaked in systemic lupus
      erythematosus patients who were aged 18 to 24 years (risk ratio 8.78, 95%
      confidence interval 3.08-24.97). CONCLUSION: Based on nationwide population-based
      data, there is an increased risk of herpes zoster in systemic lupus erythematosus
      patients compared with non-systemic lupus erythematosus patients, particularly
      among males and patients aged 18 to 24 years. Further research on the associated
      risk factors for herpes zoster in systemic lupus erythematosus patients is
      needed.

PMID- 21876971
TI  - Caries in Portuguese children with Down syndrome.
AB  - OBJECTIVES: Oral health in Down syndrome children has some peculiar aspects that
      must be considered in the follow-up of these patients. This study focuses on
      characterizing the environmental and host factors associated with dental caries
      in Portuguese children with and without Down syndrome. METHODS: A sibling
      matched, population-based, cross-sectional survey was performed. RESULTS: Down
      syndrome children presented a significantly greater percentage of children
      without caries, 78% vs. 58% of non-Down syndrome siblings. This difference in the
      DMFT index (number of decayed, missing and filled teeth) essentially reflects
      data obtained from treated teeth, for which 91% of children with Down syndrome
      had never had a tooth treated vs. 67% of siblings. This result was statistically
      significant, whereas results for decayed and lost teeth did not differ between
      Down syndrome children and their unaffected siblings. Additionally, in Down
      syndrome children, a delayed eruption of the second molar occurs. Down syndrome
      children and their siblings have similar oral hygiene habits, but a higher
      percentage of Down syndrome children visit a dentist before the age of three
      years, in comparison to their siblings. Bruxism was also more common in Down
      syndrome children compared to their siblings. CONCLUSIONS: Our results show that
      Portuguese children with Down syndrome have lower caries rates than children
      without Down syndrome. This reduced prevalence may be associated with the
      parents' greater concern about oral health care in Down syndrome children,
      resulting in their taking them sooner to visit a dentist, as well as to a higher
      bruxism prevalence and delayed tooth eruption.

PMID- 21876972
TI  - Dexmedetomidine for the prevention of shivering during spinal anesthesia.
AB  - PURPOSE: The aim of this study was to evaluate the effect of dexmedetomidine on
      shivering during spinal anesthesia. METHODS: Sixty patients (American Society of
      Anesthesiologists physical status I or II, aged 18-50 years), scheduled for
      elective minor surgical operations under spinal anesthesia with hyperbaric
      bupivacaine, were enrolled. They were administered saline (group C, n = 30) or
      dexmedetomidine (group D, n = 30). Motor block was assessed using a Modified
      Bromage Scale. The presence of shivering was assessed by a blinded observer after
      the completion of subarachnoid drug injection. RESULTS: Hypothermia was observed
      in 21 patients (70%) in group D and in 20 patients (66.7%) in group C (p =
      0.781). Three patients (10%) in group D and 17 patients (56.7%) in group C
      experienced shivering (p = 0.001). The intensity of shivering was lower in group
      D than in group C (p = 0.001). Time from baseline to onset of shivering was 10 (5
      15) min in group D and 15 (5-45) min in group C (p = 0.207). CONCLUSION:
      Dexmedetomidine infusion in the perioperative period significantly reduced
      shivering associated with spinal anesthesia during minor surgical procedures
      without any major adverse effect during the perioperative period. Therefore, we
      conclude that dexmedetomidine infusion is an effective drug for preventing
      shivering and providing sedation in patients during spinal anesthesia.

PMID- 21876973
TI  - Demographic, etiological, and histological pulmonary analysis of patients with
      acute respiratory failure: a study of 19 years of autopsies.
AB  - INTRODUCTION: Acute respiratory failure has been one of the most important causes
      of death in intensive care units, and certain aspects of its pulmonary pathology
      are currently unknown. OBJECTIVES: The objective was to describe the demographic
      data, etiology, and pulmonary histopathological findings of different diseases in
      the autopsies of patients with acute respiratory failure. METHOD: Autopsies of
      4,710 patients with acute respiratory failure from 1990 to 2008 were reviewed,
      and the following data were obtained: age, sex, and major associated diseases.
      The pulmonary histopathology was categorized as diffuse alveolar damage,
      pulmonary edema, alveolar hemorrhage, and lymphoplasmacytic interstitial
      pneumonia. The odds ratio of the concordance between the major associated
      diseases and specific autopsy findings was calculated using logistic regression.
      RESULTS: Bacterial bronchopneumonia was present in 33.9% of the cases and cancer
      in 28.1%. The pulmonary histopathology showed diffuse alveolar damage in 40.7%
      (1,917) of the cases. A multivariate analysis showed a significant and powerful
      association between diffuse alveolar damage and bronchopneumonia, HIV/AIDS,
      sepsis, and septic shock, between liver cirrhosis and pulmonary embolism, between
      pulmonary edema and acute myocardial infarction, between dilated cardiomyopathy
      and cancer, between alveolar hemorrhage and bronchopneumonia and pulmonary
      embolism, and between lymphoplasmacytic interstitial pneumonia and HIV/ AIDS and
      liver cirrhosis. CONCLUSIONS: Bronchopneumonia was the most common diagnosis in
      these cases. The most prevalent pulmonary histopathological pattern was diffuse
      alveolar damage, which was associated with different inflammatory conditions.
      Further studies are necessary to elucidate the complete pathophysiological
      mechanisms involved with each disease and the development of acute respiratory
      failure.

PMID- 21876974
TI  - The hammock: a reservoir of allergens.
AB  - INTRODUCTION: Asthma affects approximately 10% of the world's population.
      Sensitization to allergens is an important risk factor, and exposure to allergens
      is associated with disease severity. METHODS: We performed skin tests to evaluate
      allergen sensitization to mites, cockroaches, cats, dogs, and molds in 73
      asthmatic patients. Enzyme Linked Immunosorbent Assay was used to assay the mite
      and cockroach allergens found in dust from the bedding, hammocks, bedroom floors,
      living rooms, and kitchens of 29 patients and 14 controls. RESULTS: Fifty
      patients (68.5%) had positive skin test responses. There were positive responses
      to D. pteronyssinus (52.0%), B. tropicalis (53.4%), T. putrescentiae (15.0%), E.
      maynei (12.3%), L. destructor (8.2%), B. germanica (20.5%), P. americana (21.9%),
      Felis catus (10.9%), C. herbarium (2.7%), A. alternata (4.1%), and P. notatun
      (1.3%). The exposure to mite and cockroach allergens was similar in the patients
      and the controls. The Dermatophagoides pteronyssinus Group 1 levels were highest
      in the beds and hammocks. The Blattella germanica Group 1 levels were highest in
      the kitchens, living rooms and hammocks. DISCUSSION: The positive skin tests to
      mites, cockroaches and cats were consistent with previous studies. D
      pteronyssinus was the most prevalent home dust mite, and hammocks were a source
      of allergens. To improve asthma prophylaxis, it is important to determine its
      association with mite allergen exposure in hammocks.

PMID- 21876975
TI  - Interleukin-10 but not interleukin-18 may be associated with the immune response
      against well-differentiated thyroid cancer.
AB  - OBJECTIVES: The aim of this study was to investigate the role of the interleukin
      18 +105A/C and interleukin-10 -1082A/G germline polymorphisms in the development
      and outcome of differentiated thyroid carcinoma associated or not with concurrent
      thyroiditis. METHODS: We studied 346 patients with differentiated thyroid
      carcinomas, comprising 292 papillary carcinomas and 54 follicular carcinomas, who
      were followed up for 12-298 months (mean 76.10 +/- 68.23 months) according to a
      standard protocol. We genotyped 200 patients and 144 control individuals for the
      interleukin-18 +105A/C polymorphism, and we genotyped 183 patients and 137
      controls for the interleukin-10 -1082A/G polymorphism. RESULTS: Interleukin-18
      polymorphisms were not associated with chronic lymphocytic thyroiditis or any
      clinical or pathological feature of tumor aggressiveness. However, there was an
      association between the presence of interleukin-10 variants and chronic
      lymphocytic thyroiditis. Chronic lymphocytic thyroiditis was present in 21.74% of
      differentiated thyroid carcinoma patients, most frequently affecting women
      previously diagnosed with Hashimoto's thyroiditis who had received a lower 131I
      cumulative dose and did not present lymph node metastases. CONCLUSIONS: We
      conclude that the inheritance of a G allele at the interleukin-10 -1082A/G
      polymorphism may favor a concurrent thyroid autoimmunity in differentiated
      thyroid carcinoma patients, and this autoimmunity may favor a better prognosis
      for these patients.

PMID- 21876976
TI  - A new method for the assessment of patient safety competencies during a medical
      school clerkship using an objective structured clinical examination.
AB  - INTRODUCTION: Patient safety is seldom assessed using objective evaluations
      during undergraduate medical education. OBJECTIVE: To evaluate the performance of
      fifth-year medical students using an objective structured clinical examination
      focused on patient safety after implementation of an interactive program based on
      adverse events recognition and disclosure. METHODS: In 2007, a patient safety
      program was implemented in the internal medicine clerkship of our hospital. The
      program focused on human error theory, epidemiology of incidents, adverse events,
      and disclosure. Upon completion of the program, students completed an objective
      structured clinical examination with five stations and standardized patients. One
      station focused on patient safety issues, including medical error
      recognition/disclosure, the patient-physician relationship and humanism issues. A
      standardized checklist was completed by each standardized patient to assess the
      performance of each student. The student's global performance at each station and
      performance in the domains of medical error, the patient-physician relationship
      and humanism were determined. The correlations between the student performances
      in these three domains were calculated. RESULTS: A total of 95 students
      participated in the objective structured clinical examination. The mean global
      score at the patient safety station was 87.59 +/- 1.24 points. Students'
      performance in the medical error domain was significantly lower than their
      performance on patient-physician relationship and humanistic issues. Less than
      60% of students (n = 54) offered the simulated patient an apology after a medical
      error occurred. A significant correlation was found between scores obtained in
      the medical error domains and scores related to both the patient-physician
      relationship and humanistic domains. CONCLUSIONS: An objective structured
      clinical examination is a useful tool to evaluate patient safety competencies
      during the medical student clerkship.

PMID- 21876977
TI  - A close association of body cell mass loss with disease activity and disability
      in Chinese patients with rheumatoid arthritis.
AB  - OBJECTIVES: To investigate the association of body cell mass loss with disease
      activity and disability in rheumatoid arthritis patients. INTRODUCTION:
      Rheumatoid cachexia, defined as the loss of body cell mass, is important but
      under-recognized and contributes to morbidity and mortality in patients with
      rheumatoid arthritis. METHODS: One hundred forty-nine rheumatoid arthritis
      patients and 53 healthy, non-rheumatoid arthritis control subjects underwent
      anthropometric measurements of body mass index and waist and hip circumferences.
      Bioelectrical impedance analysis was used to determine the subjects' body
      compositions, including fat mass, skeletal lean mass, and body cell mass. The
      disease activity of rheumatoid arthritis was assessed using C-reactive protein
      serum, the erythrocyte sedimentation rate and the 28-joint disease activity
      score, while disability was evaluated using a health assessment questionnaire.
      RESULTS: Rheumatoid arthritis patients had lower waist-to-hip ratio (0.86 +/-
      0.07 vs. 0.95 +/- 0.06; p<0.001) and lower skeletal lean mass indexes (14.44 +/-
      1.52 vs. 15.18 +/- 1.35; p = 0.002) than those in the healthy control group.
      Compared with rheumatoid arthritis patients with higher body cell masses, those
      with body cell masses lower than median had higher erythrocyte sedimentation
      rates (40.10 +/- 27.33 vs. 25.09 +/- 14.85; p<0.001), higher disease activity
      scores (5.36 +/- 3.79 vs. 4.23 +/- 1.21; p = 0.022) and greater disability as
      measured by health assessment questionnaire scores (1.26 +/- 0.79 vs. 0.87 +/-
      0.79; p = 0.004). CONCLUSIONS: The loss of body cell mass is associated with
      higher disease activity and greater disability in rheumatoid arthritis patients.
      Body composition determined by bioelectrical impedance analysis can provide
      valuable information for a rheumatologist to more rapidly recognize rheumatoid
      cachexia in rheumatoid arthritis patients.

PMID- 21876978
TI  - Ratio of weight to height gain: a useful tool for identifying children at risk of
      becoming overweight or obese at preschool age.
AB  - PURPOSE: To analyze the usefulness of the weight gain/height gain ratio from
      birth to two and three years of age as a predictive risk indicator of excess
      weight at preschool age. METHODS: The weight and height/length of 409 preschool
      children at daycare centers were measured according to internationally
      recommended rules. The weight values and body mass indices of the children were
      transformed into a z-score per the standard method described by the World Health
      Organization. The Pearson correlation coefficients (rP) and the linear
      regressions between the anthropometric parameters and the body mass index z
      scores of preschool children were statistically analyzed (alpha = 0.05). RESULTS:
      The mean age of the study population was 3.2 years (+/- 0.3 years). The
      prevalence of excess weight was 28.8%, and the prevalence of overweight and
      obesity was 8.8%. The correlation coefficients between the body mass index z
      scores of the preschool children and the birth weights or body mass indices at
      birth were low (0.09 and 0.10, respectively). There was a high correlation
      coefficient (rP = 0.79) between the mean monthly gain of weight and the body mass
      index z-score of preschool children. A higher coefficient (rP = 0.93) was
      observed between the ratio of the mean weight gain per height gain (g/cm) and the
      preschool children body mass index z-score. The coefficients and their
      differences were statistically significant. CONCLUSION: Regardless of weight or
      length at birth, the mean ratio between the weight gain per g/cm of height growth
      from birth presented a strong correlation with the body mass index of preschool
      children. These results suggest that this ratio may be a good indicator of the
      risk of excess weight and obesity in preschool-aged children.

PMID- 21876980
TI  - Twenty-four-hour repeatability of diurnal intraocular pressure patterns in
      glaucomatous and ocular hypertensive individuals.
AB  - OBJECTIVE: To verify the 24-hour repeatability of diurnal intraocular pressure
      patterns in glaucomatous and ocular hypertensive individuals. METHODS: A
      prospective analysis of 88 eyes from 88 ocular hypertensive or open-angle
      glaucoma patients was conducted on diurnal tension curves obtained by the same
      examiner on two consecutive days. The intraclass correlation coefficient test was
      used for statistical analysis. RESULTS: Eighty-eight eyes from 88 patients were
      analyzed. Fifty-seven patients (64.8%) were female. The mean age of all
      participants was 68.7 (SD 10.8, range 51-79) years. The intraclass correlation
      coefficient values for measurements at 8 AM, 11 AM, 2 PM, and 4 PM were 0.80,
      0.82, 0.83, and 0.86, respectively (all intraclass correlation coefficient
      values, p<0.001). CONCLUSION: Diurnal intraocular pressure data collected on a
      single day characterize the diurnal intraocular pressure variability over 24
      hours in primary open-angle glaucoma and ocular hypertensive patients.

PMID- 21876979
TI  - Metabolic effects of an entero-omentectomy in mildly obese type 2 diabetes
      mellitus patients after three years.
AB  - BACKGROUND: Various digestive tract procedures effectively improve metabolic
      syndrome, especially the control of type 2 diabetes mellitus. Very good metabolic
      results have been shown with vertical gastrectomy and entero-omentectomy;
      however, the metabolic effects of an isolated entero-omentectomy have not been
      previously studied. METHODS: Nine patients with type 2 diabetes mellitus and a
      body mass index ranging from 29 to 34.8 kg/m2 underwent an entero-omentectomy
      procedure that consisted of an enterectomy of the middle jejunum and exeresis of
      the major part of the omentum performed through a mini-laparotomy. Glucagon-like
      peptide-1 and peptide YY were measured preoperatively and three months following
      the operation. Fasting and postprandial variations in glycemia, insulinemia,
      triglyceridemia, hemoglobin A1c, and body mass index were determined in the
      preoperative period and 3, 18 and, 36 months after the operation. RESULTS: All
      patients significantly improved the control of their type 2 diabetes mellitus.
      Postprandial secretion of peptide YY and Glucagon-like peptide-1 were enhanced,
      whereas hemoglobin A1c, fasting and postprandial glucose, insulin, and
      triglyceride levels were significantly reduced. Mean body mass index was reduced
      from 31.1 to 27.3 kg/m2. No major surgical or nutritional complications occurred.
      CONCLUSIONS: Entero-omentectomy is easy and safe to perform. A simple reduction
      in jejunal extension and visceral fat causes important improvements in the
      metabolic profile.

PMID- 21876981
TI  - The therapeutic effect of a pulsed electromagnetic field on the reproductive
      patterns of male Wistar rats exposed to a 2.45-GHz microwave field.
AB  - INTRODUCTION: Environmental exposure to man-made electromagnetic fields has been
      steadily increasing with the growing demand for electronic items that are
      operational at various frequencies. Testicular function is particularly
      susceptible to radiation emitted by electromagnetic fields. OBJECTIVES: This
      study aimed to examine the therapeutic effects of a pulsed electromagnetic field
      (100 Hz) on the reproductive systems of male Wistar rats (70 days old). METHODS:
      The experiments were divided into five groups: microwave sham, microwave exposure
      (2.45 GHz), pulsed electromagnetic field sham, pulsed electromagnetic field (100
      Hz) exposure, and microwave/pulsed electromagnetic field exposure. The animals
      were exposed for 2 hours/day for 60 days. After exposure, the animals were
      sacrificed, their sperm was used for creatine and caspase assays, and their serum
      was used for melatonin and testosterone assays. RESULTS: The results showed
      significant increases in caspase and creatine kinase and significant decreases in
      testosterone and melatonin in the exposed groups. This finding emphasizes that
      reactive oxygen species (a potential inducer of cancer) are the primary cause of
      DNA damage. However, pulsed electromagnetic field exposure relieves the effect of
      microwave exposure by inducing Faraday currents. CONCLUSIONS: Electromagnetic
      fields are recognized as hazards that affect testicular function by generating
      reactive oxygen species and reduce the bioavailability of androgen to maturing
      spermatozoa. Thus, microwave exposure adversely affects male fertility, whereas
      pulsed electromagnetic field therapy is a non-invasive, simple technique that can
      be used as a scavenger agent to combat oxidative stress.

PMID- 21876982
TI  - Efficacy of vitamin E and selenium for the prevention of intra-abdominal
      adhesions in rats: uterine horn models.
AB  - OBJECTIVE: This study compares the efficacies of vitamin E and selenium, both
      individually and in combination, for the prevention of postoperative intra
      abdominal adhesions in rats. METHODS: Forty-seven female rats were divided into
      five groups. The sham animals (S group, n = 7) were given only laparotomies and
      intraperitoneally received 0.9% NaCl (2 ml). In the 40 other rats, abrasions of
      the left uterine horn were performed, followed by intraperitoneal administration
      of either 2 ml 0.9% NaCl (C group), 10 mg vitamin E (vitamin E group), 0.2 mg/kg
      selenium (Se group) or 10 mg vitamin E with 0.2 mg/kg selenium (vitamin E + Se
      group), with 10 animals in each treatment group. RESULTS: Adhesion formation was
      significantly reduced in animals in the Se and vitamin E + Se groups (p<0.05).
      Tissue catalase and glutathione peroxidase activities did not significantly
      differ between the groups. However, catalase and glutathione peroxidase
      activities and reduced glutathione levels were slightly increased in the vitamin
      E, Se and vitamin E + Se groups. In the vitamin E group, malondialdehyde
      concentrations were significantly lower than in the C group (p<0.05), but no
      significant differences were present among the S, C, Se and vitamin E + Se
      groups. Levels of nitric oxide were significantly higher in the C group than in
      the other groups (p<0.01). CONCLUSION: Intraperitoneal administration of selenium
      or combined vitamin E and selenium appears to be effective in preventing intra
      abdominal adhesion formation in rat models through the reduction of lipid
      peroxidation products.

PMID- 21876983
TI  - Sildenafil preserves diastolic relaxation after reduction by L-NAME and increases
      phosphodiesterase-5 in the intercalated discs of cardiac myocytes and arterioles.
AB  - OBJECTIVES: We investigated the influence of sildenafil on cardiac contractility
      and diastolic relaxation and examined the distribution of phosphodiesterase-5 in
      the hearts of hypertensive rats that were treated with by NG-nitro-L-arginine
      methyl ester (L-NAME). METHODS: Male Wistar rats were treated with L-NAME and/or
      sildenafil for eight weeks. The Langendorff method was used to examine the
      effects of sildenafil on cardiac contractility and diastolic relaxation. The
      presence and location of phosphodiesterase-5 and phosphodiesterase-3 were
      assessed by immunohistochemistry, and cGMP plasma levels were measured by ELISA.
      RESULTS: In isolated hearts, sildenafil prevented the reduction of diastolic
      relaxation (dP/dt) that was induced by L-NAME. In addition, phosphodiesterase-5
      immunoreactivity was localized in the intercalated discs between the myocardial
      cells. The staining intensity was reduced by L-NAME, and sildenafil treatment
      abolished this reduction. Consistent with these results, the plasma levels of
      cGMP were decreased in the L-NAME-treated rats but not in rats that were treated
      with L-NAME + sildenafil. CONCLUSION: The sildenafil-induced attenuation of the
      deleterious hemodynamic and cardiac morphological effects of L-NAME in cardiac
      myocytes is mediated (at least in part) by the inhibition of phosphodiesterase-5.

PMID- 21876984
TI  - Thermographic evaluation of hind paw skin temperature and functional recovery of
      locomotion after sciatic nerve crush in rats.
AB  - INTRODUCTION: Peripheral nerves are often damaged by direct mechanical injury,
      diseases, and tumors. The peripheral nerve injuries that result from these
      conditions can lead to a partial or complete loss of motor, sensory, and
      autonomic functions, which in turn are related to changes in skin temperature, in
      the involved segments of the body. The aim of this study was to evaluate the
      changes in hind paw skin temperature after sciatic nerve crush in rats in an
      attempt to determine whether changes in skin temperature correlate with the
      functional recovery of locomotion. METHODS: Wistar rats were divided into three
      groups: control (n = 7), sham (n = 25), and crush (n = 25). All groups were
      subjected to thermographic, functional, and histological assessments. RESULTS:
      DeltaT in the crush group was different from the control and sham groups at the
      1st, 3rd and 7rd postoperative days (p<0.05). The functional recovery from the
      crush group returned to normal values between the 3rd and 4th week post-injury,
      and morphological analysis of the nerve revealed incomplete regeneration at the
      4th week after injury. DISCUSSION: This study is the first demonstration that
      sciatic nerve crush in rats induces an increase in hind paw skin temperature and
      that skin temperature changes do not correlate closely with functional recovery.

PMID- 21876985
TI  - Pharmacokinetics of cephalosporins in the neonate: a review.
AB  - The aim of this work was to review the published data on the pharmacokinetics of
      cephalosporins in neonates to provide a critical analysis of the literature as a
      useful tool for physicians. The bibliographic search was performed for articles
      published up to December 3, 2010, using PubMed. In addition, the book Neofax: A
      Manual of Drugs Used in Neonatal Care by Young and Mangum was consulted. The
      cephalosporins are mainly eliminated by the kidneys, and their elimination rates
      are reduced at birth. As a consequence, clearance is reduced and t1/2 is more
      prolonged in the neonate than in more mature infants. The neonate's substantial
      body water content creates a large volume of distribution (Vd) of cephalosporins,
      as these drugs are fairly water soluble. Postnatal development is an important
      factor in the maturation of the neonate, and as postnatal age proceeds, the
      clearance of cephalosporins increases. The maturation of the kidney governs the
      pharmacokinetics of cephalosporins in the infant. Clearance and t1/2 are
      influenced by development, and this must be taken into consideration when
      planning a cephalosporin dosage regimen for the neonate.

PMID- 21876986
TI  - Disease-modifying medications in heart failure: more than ACE inhibitors and beta
      blockers.

PMID- 21876987
TI  - Strength capacity in young patients who are receiving maintenance therapy for
      acute lymphoblastic leukemia: a case-control study.

PMID- 21876988
TI  - Thrombolysis treatment for submassive pulmonary thromboembolism in patients with
      cancer: a safe therapeutic tool.

PMID- 21876989
TI  - Hypoparathyroidism mimicking ankylosing spondylitis and myopathy: a case report.

PMID- 21876990
TI  - Coronary atherosclerotic plaque rupture following thoracic trauma: an uncommon
      cause of angina and ventricular tachycardia ("torsade de pointes").

PMID- 21876991
TI  - The management of knee dislocation in a child with Larsen syndrome.

PMID- 21876992
TI  - Pulmonary arterial involvement leading to alveolar hemorrhage in
      lymphangioleiomyomatosis.

PMID- 21876995
TI  - [Physical activity and healthy eating in Brazilian students: a review of
      intervention programs].
AB  - This article provides a systematic literature review on physical activity and/or
      healthy eating interventions among Brazilian students. Complete articles
      published from 2004 to 2009 were searched in the SciELO, MEDLINE, and CAPES
      electronic databases, in the articles' references, and through contacts with
      authors. Six studies covered nutritional interventions, another six analyzed
      nutrition and physical activity, and one discussed changes in body composition.
      Interventions produced different results according to their objectives: increase
      in weekly physical activity; improvement in eating habits and knowledge on
      nutrition; and decrease in overweight and obesity. School health promotion
      programs are essential for raising awareness on the relevance of health promotion
      and the adoption of healthy habits. However, further longitudinal studies are
      needed to produce evidence on sustainability of programs and healthy habits.

PMID- 21876996
TI  - [Alcohol consumption and associated factors in a city in Northeast Brazil].
AB  - This cross-sectional study focused on alcohol consumption according to gender,
      age, income, and schooling in Jequie, Bahia State, Brazil. The random sample
      consisted of 270 individuals over 14 years of age living in the urban area of
      Jequie from January to March 2010. Alcohol consumption was assessed using the
      Alcohol Use Disorders Identification Test (AUDIT). Of the total sample, 21.8%
      consumed four or more drinks on a typical day, 14.1% admitted having caused any
      harm after drinking, and 26.3% reported that someone had already suggested they
      should stop drinking. Forty percent of men had more than four drinks on a typical
      day, and 50.5% of young people drank frequently. Distribution of the variables
      was consistent with higher frequency and greater amounts of alcohol among men and
      young people. There was a large proportion of heavy episodic alcohol consumption.
      The study identified vulnerable groups that are still not addicted to alcohol,
      and that should be targeted for public health promotion and prevention policies.

PMID- 21876997
TI  - [Semantic equivalence and internal consistency of the Brazilian Portuguese
      version of the Sociocultural Attitudes Towards Appearance Questionnaire-3 (SATAQ
      3)].
AB  - This study aimed to describe the cross-cultural adaptation of the Sociocultural
      Attitudes Towards Appearance Questionnaire-3 (SATAQ-3) into Brazilian Portuguese.
      The methodology involved the following stages: (1) translation of the
      questionnaire into Portuguese; (2) back-translation into English; (3) meeting
      with experts to prepare a draft version; (4) assessment of verbal understanding
      of the draft by experts and by a sample of the target population; and (5)
      analysis of the tool's internal consistency, using Cronbach's alpha. The
      questionnaire was translated into Portuguese, and the scale's final version
      included 30 items, as in the original. Both the experts and target population
      members assessed all the items as easy to understand. Internal consistency was
      satisfactory, reaching 0.91 for the scale as a whole. The questionnaire has now
      been translated and adapted into Portuguese, with evidence of clear understanding
      and internal consistency. However, it is still necessary to assess its
      measurement equivalence, external validity, and reproducibility.

PMID- 21876998
TI  - [Psychosocial work-related factors and musculoskeletal pain among
      schoolteachers].
AB  - This study aimed to investigate the association between work-related psychosocial
      factors and musculoskeletal pain (MP) among primary schoolteachers in the public
      school system in Salvador, Bahia State, Brazil. A cross-sectional epidemiological
      study included all 4,496 teachers from the system. A self-applied mail
      questionnaire was used to collect information on complaints of musculoskeletal
      pain in the upper limbs, lower limbs, and back (dependent variables), demand
      control model quadrants (independent variables), and covariables. Multivariate
      logistic regression showed that teachers in high-stress jobs presented the
      highest MP rates, and that those with low-stress jobs had the lowest rates in all
      three body segments. Teachers in active jobs presented higher MP rates than those
      in low-stress jobs, particularly in the upper limbs and back. Higher MP
      prevalence rates were associated with heavier psychological demand in all three
      body segments and with limited job control in the upper limbs only.

PMID- 21876999
TI  - [Inter-sector social mobilization for dengue control in Bahia State, Brazil].
AB  - Discussions on the health-disease process and health promotion indicate the need
      to reach beyond the limits of the health sector itself to link knowledge from
      various fields in order to promote better health conditions for the population.
      Inter-sector approaches have thus emerged as a new rationale for guiding public
      policies. This study aimed to analyze the implementation of inter-sector actions
      in social mobilization for dengue control in Bahia State, Brazil, from 2008 to
      2009, using evaluative research. A log frame was developed to define criteria for
      assessing the degree of implementation of the above-mentioned actions
      (implemented; partially implemented; not implemented). The results identified
      political support from government agencies as the main positive factor for inter
      sector practices. Barriers included the concentration of responsibilities in a
      single sector and lack of planning as a work tool. The results emphasize inter
      sector linkage as a persistent challenge.

PMID- 21877000
TI  - [Prevalence of lower back pain and associated factors in students].
AB  - The objective was to determine the prevalence of lower back pain in adolescents
      and its relationship to sports and sedentary activities. We conducted a cross
      sectional study of 5th to 8th-grade students (n = 1,236) in Bauru, Sao Paulo
      State, Brazil. We used a structured protocol and the Nordic questionnaire for
      musculoskeletal symptoms. The analysis was performed using a descriptive approach
      and bivariate and multivariate binary logistic regression. Prevalence of lower
      back pain was 19.5% (7% in boys and 12.5% in girls), with statistically
      significant differences according to gender (p < 0.00001), age (p = 0.0057), and
      sports (p = 0.0001). Bivariate and multivariate analyses showed independent
      associations between lower back pain and female gender, time watching TV, and
      sports. Lower back pain in schoolchildren can persist as chronic pain in adults.
      Understanding the relationships between variables should provide useful measures
      for maintaining, improving, and promoting students' wellbeing.

PMID- 21877001
TI  - [Costs of mammogram campaigns in the Regional Health Division of Marilia, Sao
      Paulo State, Brazil, 2005-2006].
AB  - The aim of this study was to measure the direct costs of mammogram campaigns
      conducted by the Regional Health Division of Marilia, Sao Paulo State, Brazil, in
      2005 and 2006. A total of 11,952 mammograms were performed. Mammographic outcomes
      were classified according to BI-RADS. Cost analysis was based on the amount paid
      by the Brazilian Unified National Health System (SUS). Ten cases of breast cancer
      were diagnosed (0.84 per 1,000 mammograms), 70% of which between 50 and 69 years
      of age. The campaigns and follow-up cost a total of R$450,019 (U$280,000), with
      R$431,467 paid for 11,952 mammograms and R$18,552 for diagnosing 29 suspected
      cases and treating 3 cases of benign tumors and 6 cancer cases. Mean cost per
      diagnosed case was R$43,268. The high cost per diagnosed case highlights the need
      to implement effective screening programs and improve the quality of mammography
      services in this region of Sao Paulo State.

PMID- 21877002
TI  - [Indicators of physical activity and frailty in the elderly: data from the FIBRA
      study in Campinas, Sao Paulo State, Brazil].
AB  - The literature shows methodological differences in measuring physical activity in
      relation to frailty in the elderly. Therefore, the aim of the present study, part
      of FIBRA (the Frailty in Brazilian Elderly study), was to investigate
      relationships between frailty and measurements of physical activity. The study
      used a probabilistic sample of 689 elderly (72.28 +/- 5.40 years; 68.21% women).
      An adapted version of the Minnesota Leisure Time Physical Activity Questionnaire
      was used and two criteria were established for measuring physical activity:
      regular physical exercise and weekly calorie expenditure during physical exercise
      and household activities. Of the total sample, 15.09% scored on weight loss,
      17.13% on fatigue, 16.96% on low grip strength, 15.87% on slow gait, and 43.02%
      on comorbidities. According to the calorie expenditure criterion, 83.55% of the
      elders were classified as active, as compared to 45.27% according to the physical
      activity criterion. Low calorie expenditure was associated with low grip
      strength, slow gait, and advanced age. Sedentary lifestyle (limited physical
      activity) was associated with comorbidities. Calorie expenditure was more
      sensitive for measuring frailty, while physical activity was more sensitive for
      measuring health status.

PMID- 21877003
TI  - [Prevalence of wheezing and associated risk factors among infants in Recife,
      Pernambuco State, Brazil].
AB  - The aim of this study was to verify the prevalence of wheezing in infants (< 1
      year of age) in Recife, Pernambuco State, Brazil, and to identify associated risk
      factors. SAMPLE AND METHODS: the study was performed according to the protocol of
      the International Study of Wheezing in Infants (EISL) in children ranging from 12
      to 15 months of age. The sample was analyzed for presence or absence of wheezing.
      A total of 1,071 parents of children ranging from 12 to 15 months of age were
      interviewed. Prevalence of wheezing in the first year of life was 43%, with no
      difference between the sexes. Wheezing in the first year of life was associated
      with pneumonia, family history of asthma, more than nine episodes of upper airway
      infection, and the first cold before six months of age (p < 0.001). Prevalence of
      wheezing in the first year of life was high in Recife. Early onset (and high
      number) of colds, family history of asthma, and pneumonia were associated with
      wheezing in these children.

PMID- 21877004
TI  - [Organ transplantation in Brazilian States: effectiveness, productivity, and
      capacity].
AB  - This study focused on key aspects of organ transplantation programs in various
      States of Brazil. The study showed wide disparities between States, based on
      various performance indicators. States in the South, Southeast, and Midwest
      regions had the highest transplantation and productivity rates and the largest
      per capita transplantation teams. Sao Paulo proved to be a benchmark due to its
      high performance on several indicators.

PMID- 21877005
TI  - Oral health studies in the 1982 Pelotas (Brazil) birth cohort: methodology and
      principal results at 15 and 24 years of age.
AB  - The aim of this study was to describe the methodology and results of oral health
      studies nested in a birth cohort in Pelotas, Southern Brazil. For the oral health
      studies a sub-sample (n = 900) was selected from the cohort and dental
      examinations and interviews were performed at ages 15 (n = 888) and 24 years (n =
      720; 81.1%). Data collection included dental outcomes, dental care, oral health
      behaviors, and use of dental services. Mean DMF-T varied from 5.1 (SD = 3.8) to
      5.6 (SD = 4.1) in the study period. The proportion of individuals with at least
      one filled tooth increased from 51.9% to more than 70%. Individuals who had
      always been poor used dental services less and had fewer healthy teeth on average
      than those who had never been poor. Individuals with decreasing or increasing
      family income trajectories showed intermediate values. An increase was seen in
      the number of healthy teeth from age 15 to 24 only among those who had never been
      poor. A history of at least one experience with poverty had a negative impact on
      oral health in adulthood.

PMID- 21877006
TI  - [Spatial analysis of neonatal mortality and associated factors in Salvador, Bahia
      State, Brazil, 2000-2006].
AB  - An ecological study was performed to identify patterns in the spatial
      distribution of neonatal mortality and risk areas as well as associated factors
      in Salvador, Bahia State, Brazil, 2000-2006. A thematic map was constructed, and
      techniques were used for formal assessment of spatial dependence. No spatial and
      spatial regression models were used to assess possible relationships between
      selected factors and spatial distribution of neonatal mortality. Spatial
      autocorrelation was observed in neonatal mortality (I = 0.17; p = 0.0100), so its
      distribution was non-random. The analysis showed a spatial pattern in which the
      highest risk (> 9.0/1,000 live births) was concentrated in the downtown areas and
      peripheral neighborhoods with the highest concentration of low-income families,
      and this was associated with the target risk factors. The proportion of low birth
      weight newborns was the only variable that was significantly associated with
      neonatal mortality. Living conditions may have contributed to the uneven spatial
      distribution of neonatal mortality in this city.

PMID- 21877007
TI  - [Factors associated with poor self-rated health in elderly users of the Brazilian
      Unified National Health System].
AB  - This article reports on prevalence of poor self-rated health and associated
      factors among elderly users of the Brazilian Unified National Health System (SUS)
      in Goiania, Goias State, Brazil. The article is based on a cross-sectional study
      with a proportional sample of elderly in the nine health districts of Goiania.
      Data were collected after a pilot study and training of field staff. The measure
      of association was the prevalence ratio (PR) and respective confidence interval
      (95%CI). Multivariate analysis was performed using hierarchical Poisson
      regression. In 403 elderly, prevalence of poor self-rated health was 27.5%
      (95%CI: 23.2-32.2). The rate was 29.7% in women and 29.1% among seniors aged 60
      64 years. Variables associated with poor self-rated health according to
      multivariate analysis were: less than one year of schooling, lack of physical
      exercise, use of five or more medications, and recent weight loss. The results
      showed high prevalence of poor self-rated health and associated factors,
      including both adverse social conditions and individual health and lifestyle
      factors.

PMID- 21877008
TI  - [Association between types of need, human development index, and infant mortality
      in Mexico, 2008].
AB  - The aim of this study was to assess the association between different types of
      economic and social deprivation and infant mortality rates reported in 2008 in
      Mexico. We conducted an ecological study analyzing the correlation and relative
      risk between the human development index and levels of social and economic
      differences in State and national infant mortality rates. There was a strong
      correlation between higher human development and lower infant mortality. Low
      schooling and poor housing and crowding were associated with higher infant
      mortality. Although infant mortality has declined dramatically in Mexico over the
      last 28 years, the decrease has not been homogeneous, and there are persistent
      inequalities that determine mortality rates in relation to different poverty
      levels. Programs with a multidisciplinary approach are needed to decrease infant
      mortality rates through comprehensive individual and family development.

PMID- 21877009
TI  - [Alcohol consumption by university students].
AB  - Consumption of alcoholic beverages is widely encouraged by the mass media,
      despite the related health risks. Today's students in the health fields are the
      professionals of tomorrow who will be providing advice and serving as role models
      for patients. The aim of this study was to analyze alcohol consumption and
      related factors among these students. A total of 608 male and female university
      students from Maceio, the capital of Alagoas State, Brazil, completed a self
      administered questionnaire. Data analysis included Poisson regression and
      multinomial logistic models. Prevalence of lifetime use of alcohol was 90.4%.
      Prevalence of alcohol abuse was 18.3% in men and 6.1% in women. Heavier alcohol
      consumption and alcohol abuse were observed in males, older students, non-natives
      of Maceio, smokers, and those exposed to alcohol advertising. The results
      emphasized the vulnerability of these young people to risky health behaviors.
      Their future social role highlights distinct needs in their university education
      to enable them to act professionally in this area.

PMID- 21877011
TI  - [Indicators of local actions for reporting and recording cases of domestic
      violence and sexual exploitation of children and adolescents].
AB  - Information is essential for combating violence against children and adolescents
      and reclaiming their rights. This study presents indicators for the evaluation of
      local government actions for reporting and recording cases of domestic violence
      and sexual exploitation of children and adolescents, based on participatory,
      consensus-based methodologies: the nominal group technique (NGT) and the Delphi
      method. The frame of reference was the set of Brazilian policies focusing on the
      issue of violence against children and adolescence. Experts from Brazil's five
      major regions participated in the study. The consensus produced two different
      analytical scenarios, with three and 20 indicators, respectively.

PMID- 21877010
TI  - [Size at birth and mental health problems at 11 years of age in a Brazilian birth
      cohort].
AB  - The aim of this study was to evaluate the association between size at birth and
      mental health problems at 11 years of age in the 1993 Pelotas (Brazil) Birth
      Cohort Study. Newborns were weighed and measured, and anthropometric indices were
      calculated. At 11 years of age, mental health problems were assessed using the
      Strengths and Difficulties Questionnaire (SDQ). Prevalence of mental health
      problems was 32% (95%CI: 31-33). After adjusting for potential confounders,
      newborns with weight and body mass index (BMI) for age z-scores < -2 SD were at
      27% (95%CI: 7-49) and 29% (95%CI: 10-51) greater risk, respectively, of
      developing mental health problems at age 11 years than those born with normal
      scores. Newborns with BMI and head circumference for age z-scores > +2 SD were at
      34% (95%CI: 6-71) and 19% (95%CI: 1-40) greater risk, respectively, of developing
      mental health problems than those with normal scores. The results suggest that
      early factors that are reflected as size measurements at birth can cause mental
      health problems later in life.

PMID- 21877012
TI  - [Characteristics of physical and sexual violence against children and adolescents
      examined at the Forensic Medicine Institute in Maceio, Alagoas State, Brazil].
AB  - The purpose of this study was to characterize cases of violence against children
      and adolescents examined at the Forensic Medicine Institute in Maceio, Alagoas
      State, Brazil. Three hundred and three cases from September, 2008 to March, 2009,
      were analyzed. Victims were interviewed and data were collected on the type of
      violence, victim's gender, age, schooling, and economic class, maternal
      schooling, characteristics of the aggressor and person reporting the case,
      location, and repeat offenses. Violence against children and adolescents in this
      sample was concentrated in lower income groups, and girls were victimized more
      frequently than boys. Most perpetrators were non-relatives, but known to the
      family. Sexual abuse was more common among younger children, while physical
      assault was more common against adolescents. The victim's home was the most
      frequent site of the violence. Further studies are needed to determine whether
      violence in other socioeconomic groups and against males actually does not occur,
      or whether it simply is not reported to the Forensic Medicine Institute and thus
      remains invisible.

PMID- 21877013
TI  - [Estimated parameters in linkage between mortality and hospitalization databases
      according to quality of records on underlying cause of death].
AB  - The purpose of the study was to compare the linkage parameter estimates between
      hospitalization and mortality databases, calculated separately for the subsets of
      deaths from ill-defined causes and deaths from known causes. The databases for
      deaths from known causes and ill-defined causes were linked to a hospital
      admissions database. Parameters were estimated using two strategies: (1) first
      name, last name, and day, month, and year of birth, (2) full name and date of
      birth. In the first strategy, the estimates for the first and last name were at
      least 97% in both sets. However, the items day, month, and year of birth produced
      low values in both sets. In the second strategy there was an important difference
      between the two groups, with much lower values for full name and especially for
      date of birth in the group of deaths from ill-defined causes. Our results
      emphasize the need for pilot studies to evaluate possible internal heterogeneity
      of databases during the planning stage of linkage projects.

PMID- 21877014
TI  - Magnesium sulphate for fetal neuroprotection.

PMID- 21877015
TI  - [The progesterone receptor gene polymorphism as factor of risk for the preterm
      delivery].
AB  - PURPOSE: to investigate the association between gene polymorphism of the
      progesterone receptor (PROGINS) and the risk of premature birth. METHODS: In this
      case-control study, 57 women with previous premature delivery (Case Group) and 57
      patients with delivery at term in the current pregnancy and no history of preterm
      delivery (Control Group) were selected. A 10 mL amount of peripheral blood was
      collected by venipuncture and genomic DNA was extracted followed by the
      polymerase chain reaction (PCR) under specific conditions for this polymorphism
      and 2% agarose gel electrophoresis. The bands were visualized with an ultraviolet
      light transilluminator. Genotype and allele PROGINS frequencies were compared
      between the two groups by the chi2 test, with the level of significance set at
      value p < 0.05. The Odds Ratio (OR) was also used, with 95% confidence intervals.
      RESULTS: PROGINS genotypic frequencies were 75.4% T1/T1, 22.8% T1/T2 and 1.8%
      T2/T2 in the Group with Preterm Delivery and 80.7% T1/T1, 19.3% T1/T2 and 0%
      T2/T2 in the term Delivery Group. There were no differences between groups when
      genotype and allele frequencies were analyzed: p = 0.4 (OR = 0.7) and p = 0.4 (OR
      = 0.7). CONCLUSIONS: the present study suggests that the presence of PROGINS
      polymorphism in our population does not constitute a risk factor for premature
      birth.

PMID- 21877016
TI  - [Misoprostol in substitution at uterine curettage in early pregnancy failure].
AB  - PURPOSE: To evaluate the effectiveness of misoprostol administered vaginally for
      uterine evacuation in interrupted early pregnancies and the time between the
      administration and emptying correlated with gestational age. METHODS: Clinical
      trial with 41 patients with pregnancies interrupted between the 7th and the 12th
      gestational weeks. The mean age was 27.3 (+/- 6.1) years. Mean parity was 2.2 (+/
      1.2) deliveries. The average number of previous abortions was 0.2 (+/- 0.5).
      Misoprostol was administered vaginally in a single 800 ug dose and transvaginal
      ultrasound was performed after 24 hours. Abortion was considered complete when
      the anteroposterior diameter of the endometrial cavity measured < 15 mm. Patients
      whose diameter remained was larger than 15 mm underwent uterine curettage. Two
      groups (< 8 and > 8 weeks of gestational age) were compared using the binomial
      test and Student's t test regarding outcome: frequency of complete abortion and
      the interval between administration of misoprostol and abortion (in minutes). The
      level of significance was 5%. RESULTS: The mean gestational age at diagnosis was
      8.5 weeks (SD = 1.5). The intervals between administration of misoprostol and
      uterine contractions and between the administration and abortion were 322.5 +/-
      97.0 minutes and 772.5 +/- 201.0 minutes, respectively. There was complete
      abortion in 80.3%. The success rate was 96.2% for the first group and 53.3% for
      the second (p < 0.01). We observed a statistically significant difference in time
      between administration and uterine evacuation (676.2 +/- 178.9 vs. 939.5 +/-
      105.7 minutes, p < 0.01). The side effects observed were hyperthermia (12.1%),
      nausea (7.3%), diarrhea or breast pain (2.4%). No case of genital infection was
      observed. CONCLUSIONS: The use of vaginal misoprostol is a safe and effective
      alternative to curettage for interrupted early pregnancies, being better in
      pregnancies up to the 8th week. The time interval until emptying was lower in
      pregnancies that were interrupted earlier.

PMID- 21877017
TI  - [Marital problems and other factors associated with postpartum psychiatric
      disorder].
AB  - PURPOSE: To study the association between postpartum psychiatric disorder and
      demographic and psychosocial, pre- and perinatal factors. METHODS: All families
      having 4-month-old infants in Vila Jardim, a district of Porto Alegre, Brazil,
      born at a public hospital from November 1998 through December 1999 were assessed.
      The Self-Report Questionnaire (SRQ-20) and semi-structured interviews were used
      for the psychiatric assessment that included a possible diagnosis using
      Diagnostic and Statistical Manual of Mental Disorders IV (DSM- IV) criteria.
      Relational functioning between couples, the relationship with mother's family of
      origin and social network were assessed using the DSM-IV Global Assessment of
      Relational Functioning Scale (GARF). RESULTS: A total of 148 mothers and 116
      cohabiting fathers were assessed. According to the SRQ, 34.4% of the mothers and
      25.4% of the fathers had a suspicion of psychiatric disorder. Clinical
      assessments using DSM-IV criteria detected larger numbers. In the analysis of the
      whole group of women, low family income (OR = 0.8; p < 0.05) and presence of
      previous maternal disorder (OR = 2.2; p < 0.05) were associated. When only women
      living with partners were assessed (n = 116), there was an exclusive association
      with quality of marital relationship (OR = 7.3; p < 0.05). CONCLUSION: This study
      reinforces the need of investigating the presence of maternal psychiatric
      disorder during prenatal care, introduces data about the father, and especially,
      the importance of routine assessment of the marital relationship.

PMID- 21877018
TI  - [Analysis of the combined first trimester screening for chromosomal
      abnormalities].
AB  - PURPOSE: to evaluate the performance of the combined first trimester screening
      for chromosomal abnormalities in a group of the Brazilian population. METHODS: a
      retrospective study including pregnant women with single fetuses referred to a
      fetal medicine center to perform the first trimester screening that combines
      maternal age, nuchal translucency measurement and two maternal serum biochemical
      markers: free B-hCG and PAPP-A. To evaluate the performance of the test, the
      detection rate, specificity, negative and positive predicted values and false
      positive rates were calculated, considering as high risk the cut-off value above
      1 in 300. RESULTS: we studied 456 patients submitted to the test. Advanced
      maternal age above 35 years was observed in 36.2% of cases. The incidence of
      chromosomal abnormalities in the study population was 2.2%. Twenty-one patients
      (4.6%) presented a high risk (above 1:300) by the combined test. Using this cut
      off level, the detection rate of the test was 70% for all chromosomal
      abnormalities and 83.3% for trisomy 21, for a false-positive rate of 3.1%.
      CONCLUSIONS: the combined first trimester screening was effective to detect
      chromosomal abnormalities, mainly for trisomy 21, with low false-positive rates.
      The combined test contributed to decreasing the indication of an invasive test if
      we compare to maternal age alone as a risk factor.

PMID- 21877019
TI  - [Risk factors for osteoporosis in postmenopausal women from southeast Brazilian].
AB  - PURPOSE: To evaluate bone mineral density (BMD) and their risk factors associated
      with postmenopausal osteoporosis. METHODS: A cross-sectional clinical study was
      performed on 431 women (aged 40-75 years). INCLUSION CRITERIA: amenorrhea > 12
      months and age > 45 years or, bilateral oophorectomy > 40 years with BMD values
      (T-score of lumbar spine/femur neck) by DXA of the last 12 months. Risk factors
      evaluated: age, age and time of menopause, smoking, physical activity (30 min/5
      times/week), rheumatoid arthritis (RA), use of corticotherapy and hormone therapy
      (HT), previous fracture, maternal hip fracture and body mass index (BMI =
      weight/height2). The chi2 test and the logistic regression method (Odds Ratio-
      OR) were used to determine osteoporosis risk. RESULTS: According to WHO criteria,
      106 (24.6%) women showed osteoporosis (T-score < -2.5 DP), 188 (43.6%) osteopenia
      (-1.0/-2.4 DP), and 137 (31.8%) were normal (> -1.0 DP). Osteoporosis was
      detected in 12% of women aged 40-49 years, in 21.8% of women aged 50-59 years and
      in 45.7% of women aged > 60 years (p < 0.001). Osteoporosis occurred in 11.8% of
      women with a menopause period < 5 years, in 29.4% with a menopause period from 6
      to 10 years, and in 41% of women with a menopause period > 10 years (p < 0.001).
      Of the women with early menopause, 80% showed osteopenia/osteoporosis (p = 0.03),
      and of those with BMI < 20 kg/m2, 50% were osteoporotic (p < 0.001). The risk for
      osteoporosis detection increased with age (OR = 1.1; CI 95% = 1.0-1.1), time of
      menopause (OR = 1.1; CI 95% = 1.0-1.1), smoking (OR = 1.9; CI 95% = 1.2-3.2), RA
      (OR = 3.6; CI 95% = 1.3-9.6) and maternal fracture history (OR = 2.1; CI 95% =
      1.1-3.0) (p < 0.05). In contrast, HT use (OR = 0.3; 95% CI = 0.2-0.6) and high
      BMI (OR = 0.9; 95% CI = 0.8-0.9) reduced the risk (p < 0.05). CONCLUSION: In
      postmenopausal women, age, time of menopause, smoking and maternal history of
      fracture were clinical indicators of risk for osteoporosis, whereas HT use and
      high BMI proved to be protective factors.

PMID- 21877020
TI  - [Associated factors with discontinuation use of combined oral contraceptives].
AB  - PURPOSE: Due to the scarce information available in Brazil in relation to the
      number of women who initiated the use of combined oral contraceptives and
      prematurely discontinued, the objective was to assess the reasons for
      discontinuation of the use of several combined oral contraceptives among
      Brazilian women living in urban areas. METHODS: A cross-sectional study with 400
      gynecologists registered withy the Brazilian Federation of Obstetricians and
      Gynecologists. Each physician interviewed 10 non-pregnant, not breastfeeding, not
      amenorrheic women aged 18 to 39 years who consulted requesting combined oral
      contraceptive (COC) with a questionnaire at the beginning of use and at six
      months later. The questionnaire included sociodemographic data, type of COC
      chosen or prescribed and reasons for discontinuation when it occurred during
      follow-up. The strategy of selection allowed the inclusion of women from
      different socioeconomic strata, however, only those attended at private or
      insurance offices. The sample size was estimated at 1,427 women. RESULTS: A total
      of 3,465 interviews were conducted at the first visit and 1,699 six months later.
      The women were 20 to 29 years old, 57.3% were single and an equal proportion of
      45.0% attended high school or college. Most (60.7%) were nulligravidas and among
      those who had used some contraceptive before, 71.8% had used a COC. Among the
      more prescribed or chosen COC the most prevalent were monophasic with ethynil
      estradiol (20 ug) and regarding progestin the most prevalent was with gestodene
      (36.5%) followed by a COC with drosperinone (22.0%). At six months 63.5% still
      used COC. Among those who discontinued the main reasons were wishing to become
      pregnant (36.5%) and side effects (57.3%) and the most prevalent were headache
      (37.6%), weight gain (16.6%) and irregular bleeding (23.6%). CONCLUSIONS: The
      continuation rate of COC was low at six months and this study could contribute to
      a better counseling on the part of physicians of patients who initiate COC about
      side-events that are rare, minimal and temporary and about the benefits of COC
      use.

PMID- 21877021
TI  - [Metabolic abnormalities in polycystic ovary syndrome women: obese and non
      obese].
AB  - PURPOSE: To compare the metabolic characteristics of obese and non-obese young
      women with polycystic ovary syndrome (POS) from the Brazilian Southeast. METHODS:
      This was a cross-sectional study conducted on 218 women of reproductive age with
      a diagnosis of POS--90 non-obese women (BMI between 18.5 and 29.9 kg/m2), and 128
      obese patients (BMI > 30 kg/m2) selected at the time of diagnosis. The frequency
      of insulin resistance (IR), glucose intolerance (GI), metabolic syndrome (MetS)
      and type 2 diabetes mellitus (DM2) and mean values of total cholesterol (TC),
      triglycerides (TG), high-density (HDL) and low-density lipoproteins (LDL), were
      compared between obese and non-obese patients with POS. The two groups were also
      compared in terms of clinical and hormonal characteristics (follicle stimulating
      hormone, prolactin, thyroid stimulating hormone, total testosterone,
      dihydroepiandrostenedione sulfate, and 17-hydroxyprogesterone). Statistical
      analysis was performed using the SAS 9.0 software. Quantitative variables were
      compared by the Student's t-test (data with normal distribution) or by the Mann
      Whitney test (non-parametric distribution). Qualitative variables were compared
      by the Fisher test. The level of significance was set at 5% (p < 0.05) in all
      analyses. RESULTS: The frequency of IR, GI and MetS was significantly higher in
      obese than non-obese patients with POS (66.7, 29.9, and 63% versus 24.7, 12.2,
      and 16.4%, respectively). Obese patients had higher TC and TG levels (189.8 +/-
      35.8 mg/dL and 145.4 +/- 71.1 mg/dL, respectively) than non-obese patients (172.1
      +/- 38.4 mg/dL and 99.3 +/- 54 mg/dL, respectively). Both groups had mean HDL
      levels below 50 mg/dL. CONCLUSIONS: Young obese women with POS have a higher
      frequency of IR, GI and MS than non-obese. However, the occurrence of metabolic
      disorders is elevated also in the non-obese patients, suggesting that the
      presence of the syndrome may favor the development of metabolic comorbidities
      with potential medium- and long-term repercussions.

PMID- 21877022
TI  - Successful aging in Brazil.

PMID- 21877024
TI  - Impact of obstructive sleep apnea on cognitive performance.
AB  - OBJECTIVE: To evaluate the impact of obstructive sleep apnea (OSA) on cognition.
      METHOD: We compared the performance of 17 patients with polysomnographic
      diagnosis of OSA in brief cognitive tests to that of 20 healthy controls, matched
      for age and education. The testing battery included the Mini-Mental State
      Examination (MMSE), Brief Cognitive Screening Battery (BCSB), Digit-Symbol (DS)
      and Phonemic Verbal Fluency (FAS). Anthropometric measures and scores from the
      Epworth Sleepiness Scale were also recorded. RESULTS: OSA patients performed
      significantly worse than controls in the MMSE, in memory items from the BCSB, in
      DS and also in FAS. OSA patients also exhibited higher body mass index, increased
      neck circumference and higher scores in Epworth Sleepiness Scale than controls.
      CONCLUSION: OSA significantly impairs cognitive performance, especially within
      the domains of attention, memory and executive functioning. These deficits may be
      detected by brief and easy-to-administer cognitive tests.

PMID- 21877023
TI  - The Pieta study: epidemiological investigation on successful brain aging in Caete
      (MG), Brazil. Methods and baseline cohort characteristics.
AB  - OBJECTIVES: To present the methods and baseline characteristics of the Pieta
      study, a population-based survey investigating successful brain aging in the
      oldest-old. METHOD: The study was conducted in Caete (MG), Brazil. In 2007, 1,251
      individuals aged 75+ years were living in the city and were invited to
      participate. Participants responded to a general health questionnaire and were
      submitted to clinical, neurological, cognitive, psychiatric and functional
      evaluations. A subgroup was submitted to neuropsychological testing, blood tests
      and magnetic resonance of the skull. Individuals were classified as having
      cognitive impairment-no dementia, dementia, parkinsonism, psychiatric disorders
      or successful brain aging. RESULTS: We evaluated 639 individuals (51.1% of the
      target population; 64% women), aged 81.4+/-5.2 years and with 2.7+/-2.6 years of
      schooling. Almost 30% of the elderly were illiterates and 82.1% belonged to
      middle/middle-low socioeconomic levels. Almost 50% were widows, but only 14.3%
      were living alone. CONCLUSION: The Pieta cohort is representative of the oldest
      old Brazilian population. We believe the results of the study may contribute to
      increase our knowledge about healthy and pathological brain aging in the oldest
      old.

PMID- 21877025
TI  - Different cognitive profiles of Brazilian patients with relapsing-remitting and
      primary progressive multiple sclerosis.
AB  - Cognitive impairment is a symptom of multiple sclerosis (MS). Different clinical
      forms of multiple sclerosis have different cognitive profiles, according to
      findings of previous studies which used extensive batteries of neuropsychological
      tests. OBJECTIVE: To investigate cognitive profiles of Brazilian patients with
      relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple
      sclerosis (PPMS) by using a brief battery of neuropsychological tests. METHOD:
      Sixty-six patients, within 18-65 of age and 3-18 years of education, were paired
      with healthy control subjects, regarding gender, age, and education level.
      RESULTS: On Symbol Digit Modalities Test and Hooper Visual Organization Test,
      cognition was affected in 50% in RRMS and 69% in PPMS. Fluency of "F" was
      impaired in 24% of RRMS and 81% of PPMS. Immediate recall was affected in 32% of
      RRMS and in 63% of PPMS; whereas late recall, in 46% of relapsing-remitting and
      in 69% of primary progressive. CONCLUSION: Cognitive profiles of relapsing
      remitting and primary progressive patients are different.

PMID- 21877026
TI  - Cognitive impairments in patients with low grade gliomas and high grade gliomas.
AB  - OBJECTIVE: The relationship between brain tumors and cognitive deficits is well
      established in the literature. However, studies investigating the cognitive
      status in low and high-grade gliomas patients are scarce, particularly in
      patients with average or lower educational level. This study aimed at
      investigating the cognitive functioning in a sample of patients with low and high
      grade gliomas before surgical intervention. METHOD: The low-grade (G1, n=19) and
      high-grade glioma (G2, n=8) patients underwent a detailed neuropsychological
      assessment of memory, executive functions, visuo-perceptive and visuo-spatial
      abilities, intellectual level and language. RESULTS: There was a significant
      impairment on verbal and visual episodic memory, executive functions including
      mental flexibility, nominal and categorical verbal fluency and speed of
      information processing in G2. G1 showed only specific deficits on verbal and
      visual memory recall, mental flexibility and processing speed. CONCLUSION: These
      findings demonstrated different levels of impairments in the executive and memory
      domains in patients with low and high grade gliomas.

PMID- 21877027
TI  - Cerebellar atrophy is infrequently [corrected] associated with non-paraneoplastic
      sensory neuronopathy.
AB  - Sensory neuronopathies (SN) are peripheral nervous system disorders associated
      with degeneration of dorsal root ganglion neurons. Despite the evidence of a
      defective proprioceptive sensory input in SN,the prominent gait and truncal
      ataxia raises the question of a concomitant involvement of the cerebellum.
      OBJECTIVE: To evaluate cerebellar atrophy in SN. METHOD: We analyzed MRI-based
      volumetry of anterior lobe (paleocerebellum) and total cerebellum in patients
      with non-paraneoplastic chronic SN and compared to age- and gender-matched
      controls. RESULTS: Cerebellum and anterior lobe MRI volumetry were performed in
      20 patients and nine controls. Mean anterior lobe and cerebellar volume were not
      statistically different. Three patients (15%), however, had an abnormal anterior
      lobe and cerebellar volume index (values outside 2.5 standard deviations). One of
      them also had a specific atrophy of the anterior lobe. All these patients had
      infectious or dysimmune associated SN. CONCLUSION: Cerebellar atrophy is
      infrequently associated with SN, but can be found in some patients with SN
      related to infectious or immune mediated conditions. It can be more prominent in
      the anterior lobe and may contribute to the ataxia seen in these patients.

PMID- 21877028
TI  - Pressure pain threshold in the craniocervical muscles of women with episodic and
      chronic migraine: a controlled study.
AB  - OBJECTIVE: To estimate the pressure pain threshold (PPT) of the craniocervical
      muscles in women with episodic migraine (EM) n=15 and chronic migraine (CM) n=14,
      and in healthy volunteers (C) n=15. METHOD: A blinded examiner obtained the PPT
      bilaterally, by pressure algometry, for the following muscles: frontalis,
      temporalis, masseter, trapezius and sternocleidomastoid. ANOVA (p<0.05) was used
      for statistical purposes. RESULTS: Contrasted to controls, individuals with EM
      had significantly decreased PPT values for frontal muscle (EM: 2.01+/-0.67 vs. C:
      2.85+/-0.71), posterior temporalis bilaterally (right and left, respectively)
      (EM: 2.72+/-0.89 vs. C: 3.36+/-0.72 and EM: 2.60+/-1.00 vs. C: 3.35+/-0.85),
      upper trapezius bilaterally (EM: 2.69+/-1.00 vs. C: 3.49+/-0.83 and EM: 2.54+/
      0.93 vs. C: 3.32+/-0.97) and women with CM: on frontal muscle bilaterally (CM:
      2.16+/-0.52 vs. C: 2.79+/-0.71 and CM: 2.01+/-0.67 vs. C: 2.85+/-0.71) and upper
      trapezius (CM: 2.66+/-0.84 vs. C: 3.32+/-0.97), however, it was not verified
      differences between PPT values between EM and CM groups. CONCLUSION: PPT is
      decreased in women with migraine relative to controls. Future studies should
      explore this parameter as a biological marker of the disease and a predictor of
      treatment.

PMID- 21877029
TI  - Course of migraine during pregnancy among migraine sufferers before pregnancy.
AB  - OBJECTIVE: To describe the course of migraine without aura and migraine with aura
      during pregnancy and factors that could influence its course, among migraine
      sufferers before pregnancy. METHOD: A cross sectional study undertaken at the
      IMIP, Brazil. Out of 686 consecutively assisted women, at the first postnatal
      week, 266 were identified as migraine sufferers before pregnancy. RESULTS: There
      was migraine remission in 35.4%, 76.8% and 79.3% among migraine without aura
      sufferers and 20.7%, 58.6% and 65.5% among those with migraine with aura,
      respectively in the first, second and third trimesters. Statistically significant
      difference was found when the first trimester was compared with the second and
      third trimesters. The factors associated with the presence of migraine during
      pregnancy were: multiparity, menstrually related migraine without aura prior to
      pregnancy and illness during pregnancy. CONCLUSION: The study contributed to
      elucidate the course of migraine during pregnancy in migraine sufferers prior to
      pregnancy.

PMID- 21877030
TI  - Headache is associated with lower alcohol consumption among medical students.
AB  - The aim of this study was to investigate the association between headache and
      alcohol consumption among medical students. 480 medical students were submitted
      to a questionnaire about headaches and drinking alcohol. Headache was assessed by
      ID-Migraine and functional disability was evaluated with MIDAS. The evaluation of
      alcohol consumption was assessed with Alcohol Use Disorders Identification Test
      (AUDIT). There was significantly lower proportion of students with drinking
      problem among students with headache. This occurred both among students
      classified as having migraine and among those who had non-migrainous headache.
      There was not a correlation between functional disability of headache and AUDIT
      score. Our data suggest that having headache leads to a reduction in alcohol
      consumption among medical students regardless the degree of headache functional
      impact.

PMID- 21877031
TI  - Correlations between motor and sensory functions in upper limb chronic
      hemiparetics after stroke.
AB  - OBJECTIVE: Describe the somatosensory function of the affected upper limb of
      hemiparetic stroke patients and investigate the correlations between measurements
      of motor and sensory functions in tasks with and without visual deprivation.
      METHOD: We applied the Fugl-Meyer Assessment (FMA), Nottingham Sensory Assessment
      (NSA), and several motor and sensory tests: Paper manipulation (PM), Motor
      Sequences (MS), Reaching and grasping (RG) Tests Functional (TF), Tactile
      Discrimination (TD), Weight Discrimination (WD) and Tactile Recognition of
      Objects (RO). RESULTS: We found moderate correlations between the FMA motor
      subscale and the tactile sensation score of the NSA. Additionally, the FMA
      sensitivity was correlated with the NSA total; and performance on the WD test
      items correlated with the NSA. CONCLUSION: There was a correlation between the
      sensory and motor functions of the upper limb in chronic hemiparetic stroke
      patients. Additionally, there was a greater reliance on visual information to
      compensate for lost sensory-motor skills.

PMID- 21877032
TI  - Quality of life and psychomotor profile of children with attention deficit
      hyperactivity disorder (ADHD).
AB  - The knowledge of psychomotor development of children with attention deficit
      hyperactivity disorder (ADHD) may help in defining therapeutic approaches in
      order to minimize losses in their quality of life. The study objectives were to
      evaluate the quality of life and psychomotor profile of children with ADHD and
      check your correlation. Fourteen children, from seven to ten years, with ADHD
      combined type were evaluate using the scales PedsQLTM and Motor Development
      Scale. Results showed adverse effects of ADHD on quality of life and a deficit in
      motor skills. Nine participants (64.2%) were classified in motor development as
      "Normal Medium", followed by the classification "Normal Low" in four (28.5%) and
      "Low" in one subject (7.1%). We observed a positive correlation between quality
      of life and psychomotor development of children with ADHD, especially in areas:
      fine motor and spatial organization with social and psychosocial aspects, gross
      motor control with the emotional and temporal organization with the emotional,
      psychosocial and overall quality of life.

PMID- 21877033
TI  - Reliability and validity of a scale for measurement of trunk mobility in
      Parkinson's disease: Trunk Mobility Scale.
AB  - Axial rigidity is an important motor manifestation in Parkinson's disease (PD).
      Trunk mobility impairment can cause gait, balance and postural problems. However,
      only few instruments analyze the trunk mobility in PD patients. The aim of this
      study is to present a new Trunk Mobility Scale (TMS) and its validation in PD.
      The TMS constituted of dynamic tests involving trunk movements in sagittal,
      transversal and coronal planes. Ninety eight PD patients and 31 normal controls
      were analyzed. A strong correlation was found between the TMS scores and the
      Hoehn & Yahr staging scale (r: 0.72; p<0.01), motor Unified Parkinson's Disease
      Rating Scale (r: 0.84; p<0.01) and Schwab and England Activities of Daily Living
      (r: -0.72; p<0.01). The scale showed a satisfactory reliability rate
      (alphaCronbach: 0.85, ICC: 099). TMS is a simple and reliable instrument to
      evaluate trunk mobility impairment in patients with PD.

PMID- 21877034
TI  - Decision-making impairment in obsessive-compulsive disorder as measured by the
      Iowa Gambling Task.
AB  - OBJECTIVE: This study aims to evaluate the process of decision-making in patients
      with obsessive-compulsive disorder (OCD) using the Iowa Gambling Task (IGT). In
      addition, we intend to expand the understanding of clinical and demographic
      characteristics that influence decision-making. METHOD: Our sample consisted of
      214 subjects (107 diagnosed with OCD and 107 healthy controls) who were evaluated
      on their clinical, demographic and neuropsychological features. Moreover, the
      Iowa Gambling Task (IGT), a task that detects and measures decision-making
      impairments, was used. RESULTS: We found that OCD patients performed
      significantly worse on the IGT. Furthermore, features such as symptoms of anxiety
      did not influence IGT performance. CONCLUSION: Impaired decision-making seems to
      be a key feature of OCD. Given that OCD is a complex heterogeneous disorder,
      homogeneous groups are necessary for an accurate characterization of our
      findings.

PMID- 21877035
TI  - Clinical and electroencephalographic characteristics of benign occipital epilepsy
      of childhood in two tertiary Brazilian hospitals.
AB  - This study intended to investigate the clinical and electroencephalographic
      benign occipital epilepsy of childhood (BOEC) characteristics in a population
      sample of patients from two tertiary Brazilian hospitals. We analyzed
      retrospectively 4912 electroencephalograms (EEGs) records, and the included
      patients were submitted to a new clinical and EEG evaluation. Were included 12
      (0.92%) patients; 4 (33.3%) with criteria for early BOEC; 6 (50%) for late form
      and 2 (16.7%) with superimposed early and late onset forms. After new
      investigation, 2 (16.7%) had normal EEG; 4 (33.3%) had paroxysms over the
      occipital region; 3 (25%) over the temporal posterior regions and 3 (25%) over
      the posterior regions. Sharp waves were the predominant change, occurring in 8
      (66.6%); spike and slow wave complexes in 1 (8.3%) and sharp and slow wave
      complexes in 1 (8.3%). Vomiting, headache and visual hallucinations were the most
      common ictal manifestations, presented in 100% of patients with superimposed
      forms. Vomiting were absent in the late form and headache was present in all
      forms of BOEC.

PMID- 21877036
TI  - The importance of the preoperative clinical parameters and the intraoperative
      electrophysiological monitoring in brachial plexus surgery.
AB  - OBJECTIVE: The study aims to demonstrate the impact of some preoperative clinical
      parameters on the functional outcome of patients sustaining brachial plexus
      injuries, and to trace some commentaries about the use of intraoperative
      monitoring techniques. METHOD: A retrospective study one hundred cases of
      brachial plexus surgery. The analysis regarding postoperative outcomes was
      performed by comparing the average of the final result of the surgery for each
      studied cohort. RESULTS: Direct electrical stimulation was used in all patients,
      EMG in 59%, SEPs in 37% and evoked NAPs in 19% of the cases. Patients in whom the
      motor function of the hand was totally or partially preserved before surgery, and
      those in whom surgery was delayed less than 6 months demonstrated significant
      (p<0.05) better outcomes. CONCLUSION: The preoperative parameters associated to
      favorable outcomes in reconstruction of the brachial plexus are a good post
      traumatic status of the hand and a short interval between injury and surgery.

PMID- 21877037
TI  - Brachial plexus surgery: the role of the surgical technique for improvement of
      the functional outcome.
AB  - OBJECTIVE: The study aims to demonstrate the techniques employed in surgery of
      the brachial plexus that are associated to evidence-based improvement of the
      functional outcome of these patients. METHOD: A retrospective study of one
      hundred cases of traumatic brachial plexus injuries. Comparison between the
      postoperative outcomes associated to some different surgical techniques was
      demonstrated. RESULTS: The technique of proximal nerve roots grafting was
      associated to good results in about 70% of the cases. Significantly better
      outcomes were associated to the Oberlin's procedure and the Sansak's procedure,
      while the improvement of outcomes associated to phrenic to musculocutaneous nerve
      and the accessory to suprascapular nerve transfer did not reach statistical
      significance. Reinnervation of the hand was observed in less than 30% of the
      cases. CONCLUSION: Brachial plexus surgery renders satisfactory results for
      reinnervation of the proximal musculature of the upper limb, however the same
      good outcomes are not usually associated to the reinnervation of the hand.

PMID- 21877038
TI  - Critical analysis of extra peritoneal antero-lateral approach for lumbar plexus.
AB  - Lesions of lumbar plexus are uncommon and descriptions of surgical access are
      derived from vertebral spine approaches. METHOD: The extraperitoneal
      anterolateral approach to the lumbar plexus was performed in six adult fresh
      cadavers. The difficulties on dissection were related. RESULTS: An exposure of
      all distal elements of lumbar plexus was possible, but a cranial extension of the
      incision was needed to reach the iliohypogastric nerve in all cases. Ligation of
      vessels derived from common iliac artery was necessary for genitofemoral and
      obturator nerves exposure in two cases. The most proximal part of the lumbar
      roots could be identified only after dissection and clipping of most lumbar
      vessels. CONCLUSION: The extraperitoneal anterolateral approach allows
      appropriate exposure of terminal nerves of lumbar plexus laterallly to psoas
      major muscle. Cranial extension of the cutaneous incision may be necessary for
      exposure of iliohypogastric nerve. Roots exposure increases the risk of vascular
      damage.

PMID- 21877039
TI  - Trigone ventricular meningiomas: surgical approaches.
AB  - OBJECTIVE: Report our experience with trigone ventricular meningiomas and review
      the surgical approaches to the trigone. METHOD: From 1989 to 2006, six patients
      with meningiomas of the trigone of the lateral ventricles underwent microsurgical
      resection. Their clinical features, image, follow up, and surgical approaches
      were retrospectively analyzed. RESULTS: Five patients presented with large and
      one with small volume meningioma. Unspecific symptoms occurred in three patients;
      intracranial hypertension detected in three patients; homonymous hemianopsy in
      three; and motor deficit present in one patient. Three patients were operated by
      transparietal transcortical approach, two by middle temporal gyrus approach, and
      one by parieto-occipital interhemispheric precuneus approach. Total resection was
      achieved in all patients without additional deficits. CONCLUSION: Judicious
      preoperative plan, adequate knowledge of anatomy, and use of correct
      microsurgical techniques are fundamental in achieving complete resection of
      trigone meningioma with low morbidity.

PMID- 21877040
TI  - Diagnosis of, surgical technique for and treatment results from medullary lipomas
      associated with spinal dysraphism: experience with 38 patients.
AB  - OBJECTIVE: To observe whether microsurgical removal of medullary lipomas and
      untethering of the medulla is a safe and efficient procedure. METHOD: A
      retrospective study was carried out on 38 patients with medullary lipomas
      associated with spinal dysraphism who underwent operations between January 1986
      and January 2008, at the Neurosurgery Department of the Federal Hospital for
      State Public Servants, in Rio de Janeiro. RESULTS: No deaths occurred in this
      series, and there was no worsening of motor or bladder function among the
      patients. Seven individuals presented improvements in their motor deficit. Nine
      patients presented improvements in bladder function. Three individuals with
      trophic lesions achieved wound healing. CONCLUSION: Microsurgical removal of
      medullary lipomas associated with spinal dysraphism proved to be a safe procedure
      without deaths and with a low morbidity rate, and several patients achieved
      improvements in their neurological symptoms.

PMID- 21877041
TI  - Functional electrical stimulation improves brain perfusion in cranial trauma
      patients.
AB  - OBJECTIVE: Demonstrate brain perfusion changes due to neuronal activation after
      functional electrical stimulation (FES). METHOD: It was studied 14 patients with
      hemiplegia who were submitted to a program with FES during fourteen weeks. Brain
      perfusion SPECT was performed before and after FES therapy. These patients were
      further separated into 2 groups according to the hemiplegia cause: cranial trauma
      and major vascular insults. All SPECT images were analyzed using SPM. RESULTS:
      There was a significant statistical difference between the two groups related to
      patient's ages and extent of hypoperfusion in the SPECT. Patients with cranial
      trauma had a reduction in the hypoperfused area and patients with major vascular
      insult had an increase in the hypoperfused area after FES therapy. CONCLUSION:
      FES therapy can result in brain perfusion improvement in patients with brain
      lesions due to cranial trauma but probably not in patients with major vascular
      insults with large infarct area.

PMID- 21877042
TI  - NMO-DBr: the Brazilian Neuromyelitis Optica Database System.
AB  - OBJECTIVE: To present the Brazilian Neuromyelitis Optica Database System (NMO
      DBr), a database system which collects, stores, retrieves, and analyzes
      information from patients with NMO and NMO-related disorders. METHOD: NMO-DBr
      uses Flux, a LIMS (Laboratory Information Management Systems) for data
      management. We used information from medical records of patients with NMO
      spectrum disorders, and NMO variants, the latter defined by the presence of
      neurological symptoms associated with typical lesions on brain magnetic resonance
      imaging (MRI) or aquaporin-4 antibody seropositivity. RESULTS: NMO-DBr contains
      data related to patient's identification, symptoms, associated conditions, index
      events, recurrences, family history, visual and spinal cord evaluation,
      disability, cerebrospinal fluid and blood tests, MRI, optic coherence tomography,
      diagnosis and treatment. It guarantees confidentiality, performs cross-checking
      and statistical analysis. CONCLUSION: NMO-DBr is a tool which guides
      professionals to take the history, record and analyze information making medical
      practice more consistent and improving research in the area.

PMID- 21877043
TI  - Intracranial depth electrodes implantation in the era of image-guided surgery.
AB  - The advent of modern image-guided surgery has revolutionized depth electrode
      implantation techniques. Stereoelectroencephalography (SEEG), introduced by
      Talairach in the 1950s, is an invasive method for three-dimensional analysis on
      the epileptogenic zone based on the technique of intracranial implantation of
      depth electrodes. The aim of this article is to discuss the principles of SEEG
      and their evolution from the Talairach era to the image-guided surgery of today,
      along with future prospects. Although the general principles of SEEG have
      remained intact over the years, the implantation of depth electrodes, i.e. the
      surgical technique that enables this method, has undergone tremendous evolution
      over the last three decades, due the advent of modern imaging techniques,
      computer systems and new stereotactic techniques. The use of robotic systems, the
      constant evolution of imaging and computing techniques and the use of depth
      electrodes together with microdialysis probes will open up enormous prospects for
      applying depth electrodes and SEEG both for investigative use and for therapeutic
      use. Brain stimulation of deep targets and the construction of "smart" electrodes
      may, in the near future, increase the need to use this method.

PMID- 21877044
TI  - Sporadic amyotrophic lateral sclerosis: new hypothesis regarding its etiology and
      pathogenesis suggests that astrocytes might be the primary target hosting a still
      unknown external agent.
AB  - This article briefly describes the already known clinical features and pathogenic
      mechanisms underlying sporadic amyotrophic lateral sclerosis, namely
      excitoxicity, oxidative stress, protein damage, inflammation, genetic
      abnormalities and neuronal death. Thereafter, it puts forward the hypothesis that
      astrocytes may be the cells which serve as targets for the harmful action of a
      still unknown environmental agent, while neuronal death may be a secondary event
      following the initial insult to glial cells. The article also suggests that an
      emergent virus or a misfolded infectious protein might be potential candidates to
      accomplish this task.

PMID- 21877045
TI  - Sudden death in a child with epilepsy: potential cerebellar mechanisms?
AB  - Epilepsy is the most common neurological disorder in humans. People with epilepsy
      are more likely to die prematurely than those without epilepsy, with the most
      common epilepsy-related category of death being sudden unexpected death in
      epilepsy (SUDEP). The central mechanisms underlying the fatal process remain
      unclear, but cardiac and respiratory mechanisms appear to be involved. Recently,
      cerebellar, thalamic, basal ganglia and limbic brain structures have been shown
      to be implicated in respiratory and cardiac rate regulation. We discuss here the
      potential mechanisms underlying the fatal process, with a description of
      cerebellar actions likely failing in that SUDEP process.

PMID- 21877046
TI  - Americo Negrette and Huntington's disease.
AB  - The authors present a historical review of the seminal clinical contribution of
      Professor Americo Negrette, a Venezuelan neurologist, to the evolution of
      scientific knowledge about Huntington's disease.

PMID- 21877047
TI  - Wittgenstein, medicine and neuropsychiatry.
AB  - A historical review is presented of the link between Ludwig Wittgenstein,
      considered the most important philosopher of the 20th century, and medicine,
      particularly neurology and psychiatry. Wittgenstein worked as a porter at Guy's
      Hospital in London, and then as a technician at the Royal Victoria Infirmary in
      Newcastle. He wrote about his important insights into language, and neuroscience.
      It has been suggested that he had Asperger syndrome and a possible movement
      disorder (mannerisms).

PMID- 21877048
TI  - Leukoencephalopathy, cerebral calcifications, and cysts: entity that can mimic a
      neoplasm.

PMID- 21877049
TI  - Pial arteriovenous fistula in the posterior fossa.

PMID- 21877050
TI  - Extradural cavernous hemangioma of thoracic spine.

PMID- 21877051
TI  - Bilateral traumatic avulsion of abducens nerve.

PMID- 21877052
TI  - Supratentorial tanycytic ependymoma: an uncommon fibrillary ependymoma variant.

PMID- 21877053
TI  - Hyperintense basal ganglia on MR imaging in hematopoietic stem cell
      transplantation recipient.

PMID- 21877054
TI  - Lumbar mass as the presentation form of a tuberculous spondylodiscitis.

PMID- 21877060
TI  - Functional electrical stimulation training on functional capacity and blood
      pressure variability in a centenarian woman: case study.
AB  - BACKGROUND: Functional electrical stimulation (FES) is a rehabilitation method
      that can revert alterations provoked by aging, such as reductions in functional
      capacity and modifications on blood pressure variability (BPV). OBJECTIVES: To
      evaluate the training effects of FES on functional capacity and BPV in a
      centenarian woman. METHODS: A 101-year-old woman without previous disease
      underwent FES training for 12 weeks, with three 40 min sessions/week. FES was
      applied at a frequency of 20 Hz with a 0.5 ms pulse, 5 s contraction time, 10 s
      relaxation time, the maximum tolerable intensity and with progressive overload.
      Functional capacity was assessed with a six-minute walk test (6MWT) and proximal
      lower limb strength was assessed with a sit-and-stand test (STST). BPV was
      measured by continuous recording of pulse pressure and calculated by spectral
      analysis. All variables were measured before and after FES training. RESULTS:
      After training there was a 70% increase in distance walked in the 6MWT, a 300%
      increase in the number of STST repetitions, an 8 mmHg reduction in systolic blood
      pressure (SBP) and a 4 mmHg reduction in diastolic blood pressure (DBP) and mean
      blood pressure (MBP). Reductions in SBP (11.8 mmHg2), DBP (2.3 mmHg2) and MBP
      (6.0 mmHg2) variability were also observed. CONCLUSIONS: Three months of FES
      training improved functional capacity and BPV in a centenarian woman.

PMID- 21877061
TI  - Influence of the number of layers of paris bandage plasters on the mechanical
      properties speciments used on orthopedic splints.
AB  - OBJECTIVE: To evaluate the effects of varying numbers of layers of plaster of
      Paris bandages on the mechanical properties of specimens used on the construction
      of orthopedic splints. METHODS: Rectangular plate-shaped and cylinder-shaped
      specimens were constructed and assigned to two groups simulating plaster slabs
      and cast and further divided into six subgroups according to the number of layers
      used: 3, 6, 8, 10, 12 and 14 layers. The specimens were subjected to either a
      three-point bending test (plates/slab) or compressive strength test
      (cylinders/cast). The following mechanical properties were evaluated: maximum
      load, elastic limit load and stiffness. Specimen weight was also calculated. Data
      was analyzed using Kruskal-Wallis and the least significant difference (LSD)
      tests. RESULTS: Pairwise comparisons of the subgroups 10x12 and 10x14 revealed
      significant differences for all mechanical properties (p<0.05). The results of
      this study suggest that when the goal is to construct appliances with high
      mechanical strength, regardless of weight, such as serial plaster slabs splints
      for stimulating tissue growth through the application of gradual load, splints
      made with plaster of Paris bandages with 12 or 14 layers should be preferred. For
      orthotic devices such as positioning orthotics, the use of 10 layers plaster
      bandages slab splints is advisable as they were found to have better correlation
      between mechanical strength and weight in comparison to those made wtih 6 or 8
      layers. CONCLUSION: Based on the findings of this study, we suggest the use of 10
      layers of plaster of Paris for the construction of orthopedic splints.

PMID- 21877062
TI  - Beliefs about the use of baby walkers.
AB  - OBJECTIVES: To understand the opinion of the parents about the baby walker and
      compare the age of gait acquisition between infants that used a walker and those
      that did not. METHODS: In this quali-quantitative study, an interview involving a
      semi-structured questionnaire was carried out with 26 parents, 14 of whose
      infants used the equipment (BWG) and 12 of whose infants did not (NBWG) prior to
      gait acquisition. After extensive content analysis, categories for interpreting
      the results emerged. For data triangulation, the age of gait acquisition was
      documented by weekly telephone contact. Student's t-test was used for comparison
      between groups with a significance level of alpha=0.05. RESULTS: The following
      categories were identified in the parents' reports: a) information about the baby
      walker; b) doubt/decision to use it vs. certainty about not using it; c) beliefs
      about the use of a baby-walker; and d) benefits and harm from use. The age of
      independent gait acquisition did not differ between groups (p=0.837): BWG
      initiated gait at 376.17 (SD=32.62) days and NBWG did so at 378.75 (SD=27.99)
      days. CONCLUSIONS: The beliefs and feelings that permeate the decision to use a
      baby walker illustrate the different rationales adopted by parents about the role
      of this equipment in the child's development of gait and autonomy. The use of a
      baby walker did not influence the age of gait acquisition. The results broaden
      the understanding of choices that influence child-rearing practices prior to gait
      acquisition.

PMID- 21877063
TI  - How do low/high height and weight variation affect upper limb movements during
      manual material handling of industrial boxes?
AB  - OBJECTIVES: To evaluate the effect of surface height and load weight on upper
      limb movements and electromyographic (EMG) recordings during manual handling
      performed by both experienced and inexperienced lifter subjects. METHODS: Sixteen
      experienced and sixteen inexperienced lifters handled a box (both 7 and 15 kg)
      from an intermediate height (waist level) to either a high or low surface.
      Electromyography and video images were recorded during the tasks. The 10th, 50th
      and 90th percentiles were calculated for the deltoid and biceps muscles, shoulder
      flexion, shoulder abduction, and elbow flexion movements. Groups, right/left
      sides, weights and heights were compared. There were no differences between
      either groups or sides. RESULTS: Weight and height variations affected EMG and
      posture, although weight had more impact on EMG. Shoulder abduction and flexion
      movements higher than 60o occurred, particularly for the higher surface. Shoulder
      flexion was also higher when the box was moved to the low height. This study
      provides new evidence as shoulder postures during boxes handling on low surfaces
      had not previously been evaluated. CONCLUSIONS: The high demand of upper limb in
      manual material handling tasks is clear, particularly for the shoulder. This
      knowledge can be used by physical therapists to plan better rehabilitation
      programs for manual material handling-related disorders, particularly focusing on
      return to work.

PMID- 21877064
TI  - Investigation of the occurrence of Mansonella ozzardi in the State of Rondonia,
      Western Amazonia, Brazil.
AB  - INTRODUCTION: Mansonella ozzardi, a human filarial nematode transmitted by
      Diptera Simuliidae flies (black flies), is widely spread in the Amazon, while the
      occurrence of mansonelliasis in the State of Rondonia (Western Amazonia) has not
      been reported thus far. The existence of this parasitic disease in this state is
      investigated in this study. METHODS: A total of 4,452 people who lived alongside
      the Madeira, Mamore, Guapore, Machado and Preto Rivers, in the State of Rondonia,
      were examined using the thick blood smear method. Alongside the Machado and
      Guapore rivers, 2,112 adult simuliid specimens were captured. RESULTS: Infected
      people were not reported, although simuliids with vector potential such as
      Cerqueirellum pydanielli, C. argentiscutum and C. amazonicum were found.
      CONCLUSIONS: This study registered no infected people. This finding may be
      explained by the individuals' low level of microfilaremia that is below the limit
      of detection of the diagnostic method used in the study or insufficient migration
      of people infected with M. ozzardi from endemic areas, making it impossible to
      introduce the disease into Rondonia. Further studies using more sensitive
      diagnostic techniques could shed light on this question.

PMID- 21877065
TI  - Delayed-type hypersensitivity skin test responses to PPD and other antigens among
      BCG-vaccinated HIV-1-infected and healthy children and adolescents.
AB  - INTRODUCTION: Among HIV-1-infected patients, CD4+ T cell counts are well
      established markers of cell-mediated immunity. Delayed-type hypersensitivity
      (DTH) skin tests can be used to evaluate in vivo cell-mediated immunity to common
      antigens. METHODS: DTH responses to tuberculin purified protein derivative (PPD),
      sporotrichin, trichophytin, candidin and streptokinase/streptodornase antigens
      were assessed. Thirty-six HIV-1-infected children/adolescents and 56 age- and sex
      matched HIV-1/HIV-2-seronegative participants were tested. All participants had a
      BCG scar. Fisher's exact test was used to evaluate significant differences
      between groups (p<0.05). RESULTS: The main characteristics of the HIV-1 patients
      were as follows: median age 8.1 years; 20/36 were males; 35 were vertical
      transmission cases; 34 were AIDS cases under antiretroviral therapy; median viral
      load = 3.04 log10 copies/ml; median CD4+ T cell count = 701 cells/MUl. A total of
      25% (9/36) and 87.5% (49/56) of HIV-1-infected and healthy participants,
      respectively, displayed DTH reactivity to at least one antigen (p<0.001). Among
      HIV-1-infected participants, reactivity to candidin predominated (8/36, 22.2%),
      while PPD positivity prevailed among healthy participants (40/56, 71.4%). PPD
      reactivity in the HIV-1-positive group was 8.3% (p<0.01). The median PPD
      induration was 2.5mm (range: 2-5mm) in the HIV-1 group and 6.0 mm among healthy
      participants (range: 3-15 mm). There was no correlation between PPD positivity
      and age. No correlation between CD4+ T cell counts and DTH reactivity was
      observed among HIV-1-infected patients. CONCLUSIONS: DTH skin test responses,
      including PPD reactivity, were significantly lower among HIV-1-infected
      participants compared to healthy controls, which likely reflects advanced disease
      and T cell depletion.

PMID- 21877066
TI  - [World Viral Hepatitis Day].

PMID- 21877067
TI  - [Safe blood in the absence of viral infections due to HBV, HCV and HIV in
      serological window period in donors].
AB  - OBJECTIVE: To determine the prevalence of viral infections (HBV, HCV and HIV) in
      serological window period in blood donors screened with nucleic acid testing
      (NAT). MATERIALS AND METHODS: We assessed all blood donors from July 2008 to June
      2009 at the Central Blood Bank of the Mexican Institute of Social Security.
      Medical history was made and provided an information brochure and self-exclusion
      questionnaire. All blood donors were tested with serological tests (Ag-HBVs, Anti
      HCV and Anti-HIV) and molecular testing with NAT for HBV, HCV and HIV. The window
      period was defined with the positive NAT and negative serological test. RESULTS:
      During one year, we evaluated 47 847 blood donors. None subject was identified
      with viral infection (HBV, HCV and HIV) in serological window period. Positive
      serological testing were found for HBV in 78 (0.2%), 318 (0.7%) for HCV and 155
      (0.3%) for HIV. Positive NAT was demonstrated only in donors with positive
      serology: 26 of 78 with HBV, 56 of 318 with HCV and 16 of 155 with HIV.
      CONCLUSION: This is the first study in Mexico showed no viral infections (HBV,
      HCV and HIV) during serological window period in blood donors; The medical
      history and the self-exclusion questionnaire help to improve blood transfusion
      safety.

PMID- 21877068
TI  - [Nosocomial transmission of hepatitis C associated with anesthesia procedures: a
      case-control study].
AB  - OBJECTIVE: Nosocomial transmission of hepatitis C virus (HCV) infection had been
      related with anesthesia procedures. The study aim was to measure the association
      between anesthesia procedures in cases with previous surgery and HCV infection.
      MATERIAL AND METHODS: In a case-control study were included subjects that
      attended to the Central Blood Bank of the West Medical National Center, Mexican
      Institute of the Social Security in Guadalajara, Jalisco between july 2005 and
      september 2007. Cases were patients with positive hepatitis C antibody (anti-HCV)
      confirmed by recombinant immunoblot assay (RIBA) and/or nucleic acid test (HCV
      RNA); the control group was blood donors with negative antibody. An exhaustive
      questionnaire about risk factors for hepatitis C, was applied. The risk of HCV
      infection was determined with the Odds Ratio (OR) and multivariate analysis was
      made by logistic regression. RESULTS: We included 362 subjects, 211 cases and 151
      controls; in 70 (33.2%) cases were found significant association between the
      anesthesia procedures and HCV infection in patients with previous surgery (OR
      adjusted 2.44, CI 95% 1.44 - 4.11) CONCLUSION: This is the first study in Mexico
      that demonstrate association between history of anesthesia procedures and HCV
      infection in cases with previous surgery.

PMID- 21877069
TI  - Heterogeneous distribution of hepatitis B serological markers in rural areas of
      Mexico.
AB  - OBJECTIVE: To study the distribution of the hepatitis B antibody (anti-HBc) based
      on a national serosurvey from 10 Mexican states showing a mean HBV prevalence
      higher than the national one. MATERIALS AND METHODS: This was a cross-sectional
      study. During 2003, anti-HBc was analyzed at INSP in 19 907 sera, and the related
      sociodemographic factors were determined. RESULTS: Anti-HBc prevalence was
      greater among men, but it was also associated to age, residence in a rural area,
      low socio-economic status, and illiteracy. Clusters of very high anti-HBc
      prevalence were found in several rural communities where the prevalence of anti
      HBc in adults is 3 to 20 times the national average. CONCLUSIONS: Besides a low
      endemicity of HBV in Mexico, distribution is heterogeneous as was shown in
      several of the states studied, where there are rural towns with very high
      prevalence of HBV markers. National serosurveys are useful tools for identifying
      communities with hepatitis B hyperendemicity, where focused research and control
      measures are needed.

PMID- 21877070
TI  - [Serological markers of hepatitis B and C, and HIV in La Calera and Cuambio,
      Guerrero, Mexico].
AB  - OBJECTIVE: To perform a hepatitis B, C, and HIV survey in an enhanced sample from
      two rural communities with the highest anti-HBc prevalence found in ENSA 2000.
      MATERIALS AND METHODS: This was a cross-sectional study.We studied the
      communities of La Calera and Cuambio, two adjacent rural towns of the district of
      Zirandaro, Guerrero, targeted because of the high prevalence of anti-HBc shown in
      ENSA 2000.We assessed the prevalence of hepatitis B and C, and HIV serological
      markers and associated factors among inhabitants older than 10 years. RESULTS: A
      very high prevalence of hepatitis B markers associated with socioeconomic factors
      was confirmed, while hepatitis C prevalence was low and HIV absent in the two
      communities addressed. CONCLUSIONS: National serosurveys are an accurate tool for
      identifying communities with hepatitis B high endemicity where focused research
      and control measures are needed.

PMID- 21877071
TI  - [Epidemiology of viral hepatitis in Mexico].
AB  - The main etiology of liver disease in Mexico is alcohol and viral hepatitis. The
      aim of the present study was to analyze the current epidemiology of viral
      hepatitis in Mexico. From 2000 to 2007 the Ministry of Health reported 192 588
      cases of hepatitis, 79% HAV, 3.3% HBV, 6% HCV, and 12% without a specific
      etiologic factor. Due to high endemic areas for HBV infection in native Mexican
      population, limitations in the diagnostic sensitivity and specificity of the
      serological immunoassays used to date and presence of occult hepatitis B in the
      country, the real prevalence of HBV infection could be even higher than HCV in
      Mexico. Hepatitis E virus in cirrhotic patients and in porcine farms could at
      least partially explain the cases of hepatitis that are diagnosed without a
      specific etiologic agent. Specific strategies to establish control regulations
      against viral hepatitis infections in Mexico are proposed.

PMID- 21877072
TI  - [The viral hepatitides].

PMID- 21877073
TI  - Viral hepatitis infection and insulin resistance: a review of the
      pathophysiological mechanisms.
AB  - Viral hepatitis is a common cause of morbidity in Mexico. Insulin resistance (IR)
      is related to the liver damage caused by some viral infections, especially
      chronic infections. Chronic viral infection is an important risk factor for the
      development of type 2 diabetes mellitus, disease that is currently among the 10
      main causes of morbidity and the most common cause of mortality. Although several
      studies have reported an association between IR and hepatitis B virus or
      hepatitis C virus (HCV) infection, the pathophysiology has been studied
      thoroughly only for the association between IR and HCV infection. It is thought
      that HCV infection causes direct damage through the action of the core proteins,
      which induces an inflammatory state characterized by secretion of proinflammatory
      cytokines that interfere with normal insulin signaling and disturb glucose, lipid
      and protein metabolism. This review summarizes the mechanisms by which viral
      infection is thought to induce IR.

PMID- 21877074
TI  - [Current advances in hepatitis C treatment].
AB  - Infection by hepatitis C virus constitutes an important health problem in Mexico.
      Diagnosis of high-risk population is essential given the probability of
      developing chronic disease, cirrhosis and cirrhosis decompensation, likely
      leading to the need of a liver transplant and/or the development of
      hepatocellular carcinoma. Currently, the standard of care (SOC) treatment
      includes pegylated interferon and ribavirin, which have shown an approximately
      57% rate response in genotype 1, the most prevalent in Mexico. It is known that
      between 30 and 60% of the infected population does not show a sustained
      virological response or cure. Therefore, in this article, we review existing
      therapeutic strategies in order to optimize the treatment. Future treatment
      strategies are also described. Eventually, it will be possible to add one or two
      molecules of the new directly acting antiviral drugs, to the SOC treatment. Each
      of them has a different action mechanism, and we are envisioning the possibility
      of an interferon-free therapy after 2015.

PMID- 21877075
TI  - [Hepatitis C as a public health problem in Mexico].
AB  - We report the results of a multidisciplinary seminar approaching the recognition
      and construction of hepatitis C as a health issue in Mexico. Its prevalence is
      1.4% and its incidence is estimated in 19 300 new cases per year.As transfusion
      decreases as a risk factor, the relevance of nosocomial transmission and use of
      intravenous or intranasal drugs increases. It is necessary to develop new
      contents for the social representation and risk perception of the disease.
      Response guided treatment based on PCR-RNA has modified the treatment schemes, a
      very important issue when considering policies for management. Legislation about
      hepatitis C in the country is limited. Assignments of the Federal Government and
      the federative entities in the country regarding health issues are framed in the
      13th article of the General Mexican health law. It is necessary to advance
      towards the development of a public health policy at the national level for
      hepatitis C.

PMID- 21877076
TI  - Hepatitis C seroprevalence and correlation between viral load and viral genotype
      among primary care clients in Mexico.
AB  - OBJECTIVE: To measure hepatitis C virus (HCV) sero-prevalence, prevalence,
      hepatitis risk characteristics frequency, and genotype correlation with viral
      load among clients attending health care clinics. MATERIAL AND METHODS: Venous
      blood samples from l12 226 consecutive consenting adults were collected from
      January 2006 through December 2009. HCV antibodies were detected by immunoassay.
      HCV RNA was detected by qRT-PCR and viral genotype was performed by PCR and LIPA
      test. RESULTS: The HCV seroprevalence observed was l.5 % (C.I. 95% l.3-l.7), from
      seropositive individuals 60.9 % reported previous blood transfusion, 28.3%
      declared to have relatives with cirrhosis, 25.2% had tattoos or piercings, and
      6.9% referred to have used drugs. Male gender and transfusion (p<0.001) were the
      most frequent hepatitis risk characteristics in the HCV seropositive group. Among
      seropositive subjects 48.3% presented HCV RNA.The most frequent genotype detected
      in all geographic areas of Mexico was l (subtype lA, 33%; subtype lB, 21.4%)
      followed by genotype 2 (subtype 2A, 8.50%). Subjects with genotype 1 had a
      significant correlation with the highest viral load. CONCLUSIONS: Our results
      show that nearly half of seropositive individuals are chronically infected. HCV
      infection has been shown in this study to be an emerging health problem in
      Mexico.

PMID- 21877077
TI  - [The health system of Bolivia].
AB  - This paper describes the Bolivian health system, including its structure and
      organization, its financing sources, its health expenditure, its physical,
      material and humans resources, its stewardship activities and the its health
      research institutions. It also discusses the most recent policy innovations
      developed in Bolivia: the Maternal and Child Universal Insurance, the Program for
      the Extension of Coverage to Rural Areas, the Family, Community and Inter
      Cultural Health Model and the cash-transfer program Juana Azurduy intended to
      strengthen maternal and child care.

PMID- 21877078
TI  - [The health system of Brazil].
AB  - This paper describes the Brazilian health system, which includes a public sector
      covering almost 75% of the population and an expanding private sector offering
      health services to the rest of the population. The public sector is organized
      around the Sistema Unico de Saude (SUS) and it is financed with general taxes and
      social contributions collected by the three levels of government (federal, state
      and municipal). SUS provides health care through a decentralized network of
      clinics, hospitals and other establishments, as well as through contracts with
      private providers. SUS is also responsible for the coordination of the public
      sector. The private sector includes a system of insurance schemes known as
      Supplementary Health which is financed by employers and/or households: group
      medicine (companies and households), medical cooperatives, the so called Self
      Administered Plans (companies) and individual insurance plans.The private sector
      also includes clinics, hospitals and laboratories offering services on out-of
      pocket basis mostly used by the high-income population. This paper also describes
      the resources of the system, the stewardship activities developed by the Ministry
      of Health and other actors, and the most recent policy innovations implemented in
      Brazil, including the programs saude da Familia and Mais Saude.

PMID- 21877079
TI  - [The health system of Chile].
AB  - This paper describes the Chilean health system, including its structure,
      financing, beneficiaries, and its physical, material and human resources. This
      system has two sectors, public and private. The public sector comprises all the
      organisms that constitute the National System of Health Services, which covers
      70% of the population, including the rural and urban poor, the low middle-class,
      the retired, and the self-employed professionals and technicians.The private
      sector covers 17.5% of the population, mostly the upper middle-class and the high
      income population. A small proportion of the population uses private health
      services and pays for them out-of-pocket. Around l0% of the population is covered
      by other public agencies, basically the Health Services for the Armed Forces. The
      system was recently reformed with the establishment of a Universal System of
      Explicit Entitlements, which operates through a Universal Plan of Explicit
      Entitlements (AUGE), which guarantees timely access to treatment for 56 health
      problems, including cancer in children, breast cancer, ischaemic heart disease,
      HIV/AIDS and diabetes.

PMID- 21877080
TI  - [The health system of Colombia].
AB  - This document briefly describes the health conditions of the Colombian population
      and, in more detail, the characteristics of the Colombian health system. The
      description of the system includes its structure and coverage; financing sources;
      expenditure in health; physical material and human resources available;
      monitoring and evaluation procedures; and mechanisms through which the population
      participates in the evaluation of the system. Salient among the most recent
      innovations implemented in the Colombian health system are the modification of
      the Compulsory Health Plan and the capitation payment unit, the vertical
      integration of the health promotion enterprises and the institutions in charge of
      the provision of services and the mobilization of additional resources to meet
      the objectives of universal coverage and the homologation of health benefits
      among health regimes.

PMID- 21877081
TI  - [The health system of Costa Rica].
AB  - This paper describes the Costa Rican health system which provides health, water
      and sanitation services. The health component of the system includes a public and
      a private sector. The public sector is dominated by the Caja Costarricense de
      Seguro Social (CCSS), an autonomous institution in charge of financing,
      purchasing and delivering most of the personal health services in Costa Rica.
      CCSS is financed with contributions of the affiliates, employers and the state,
      and manages three regimes: maternity and illness insurance, disability, old age
      and death insurance, and a non-contributive regime. CCSS provides services in its
      own facilities but also contracts with private providers. The private sector
      includes a broad set of services offering ambulatory and hospital care. These
      services are financed mostly out-of-pocket, but also with private insurance
      premiums. The Ministry of Health is the steward of the system, in charge of
      strategic planning, sanitary regulation, and research and technology development.
      Among the recent policy innovations we can mention the establishment of the basic
      teams for comprehensive health care (EBAIS), the de-concentration of hospitals
      and public clinics, the introduction of management agreements and the creation of
      the Health Boards.

PMID- 21877082
TI  - [The health system of Cuba].
AB  - This paper describes the health conditions in Cuba and the general
      characteristics of the Cuban health system, including its structure and coverage,
      its financial sources, its health expenditure, its physical, material and human
      resources, and its stewardship functions. It also discusses the increasing
      importance of its research institutions and the role played by its users in the
      operation and evaluation of the system. Salient among the social actors involved
      in the health sector are the Cuban Women Federation and the Committees for the
      Defense of the Revolution. The paper concludes with the discussion of the most
      recent innovations implemented in the Cuban health system, including the
      cardiology networks, the Miracle Mission (Mision Milagro) and the Battle of Ideas
      (Batalla de Ideas).

PMID- 21877083
TI  - [The health system of Ecuador].
AB  - This paper describes the health conditions in Ecuador and, in more detail, the
      characteristics of the Ecuadorian health system, including its structure and
      coverage, its financial sources, the physical, material and human resources
      available, and the stewardship activities developed by the Ministry of Public
      Health. It also describes the structure and content of its health information
      system, and the participation of citizens in the operation and evaluation of the
      health system. The paper ends with a discussion of the most recent policy
      innovations implemented in the Ecuadorian system, including the incorporation of
      a chapter on health into the new Constitution which recognizes the protection of
      health as a human right, and the construction of the Comprehensive Public Health
      Network.

PMID- 21877084
TI  - [The health system of El Salvador].
AB  - This paper describes the health conditions in El Salvador and the main
      caracteristics of the Salvadoran health system, including its structure and
      coverage, its financial sources, the physical, material and human resources
      available, the stewardship functions developed by the Ministry of Public Health,
      and the participation of health care users in the evaluation of the system. It
      also discusses the most recent policy innovations including the approval of the
      Law for the Creation of the National Health System, which intends to expand
      coverage, reduce health inequalities and improve the coordination of public
      health institutions.

PMID- 21877085
TI  - [The health system of Guatemala].
AB  - This paper describes the health conditions in Guatemala and, in more detail, the
      characteristics of the Guatemalan health system, including its structure en
      coverage, its financial sources, the stewardship functions developed by the
      Ministry of Health, as well as the generation of health information and the
      development of research activities. It also discusses the recent efforts to
      extend coverage of essential health services, mostly to poor rural areas.The most
      recent innovations also discussed in this paper include the Program for the
      Expansion of Coverage of Essential Services, the Program to Expand Access to
      Essential Drugs and the agreements between the Ministry of Health and several non
      governmental organizations to provide essential services in rural settings.

PMID- 21877086
TI  - [The health system of Honduras].
AB  - This paper describes the health system of Honduras, including its challenges,
      structure coverage, sources of financing, resources and stewardship activities.
      This system counts with a public and a private sector. The public sector includes
      the Ministry of Health (MH) and the Honduran Social Security Institute (HSSI).
      The private sector is dominated by a set of providers offering services payed
      mostly out-of-pocket. The National Health Plan 2010-2014 includes a set of
      reforms oriented towards the creation of an integrated and plural system headed
      by the MH in its stewardship role. It also anticipates the creation of a public
      health insurance for the poor population and the transformation of the HSSI into
      a public insurance agency which contracts services for its affiliates with public
      and private providers under a family medicine model.

PMID- 21877087
TI  - [The health system of Mexico].
AB  - This paper describes the Mexican health system. In part one, the health
      conditions of the Mexican population are discussed, with emphasis in those
      emerging diseases that are now the main causes of death, both in men and women:
      diabetes, ischaemic heart disease, cerebrovascular diseases and cancer. Part two
      is devoted to the description of the basic structure of the system: its main
      institutions, the population coverage, the health benefits of those affiliated to
      the different heath institutions, its financial sources, the levels of financial
      protection in health, the availability of physical, material and human resources
      for health, and the stewardship functions displayed by the Ministry of Health and
      other actors. This part also discusses the role of citizens in the monitorization
      and evaluation of the health system, as well as the levels of satisfaction with
      the rendered health services. In part three the most recent innovations and its
      impact on the performance of the health system are discussed. Salient among them
      are the System of Social Protection in Health and the Popular Health Insurance.
      The paper concludes with a brief analysis of the short- and middle-term
      challenges faced by the Mexican health system.

PMID- 21877088
TI  - [The health system of Nicaragua].
AB  - This paper describes the health conditions in Nicaragua and discusses the
      characteristics of its national health system including its structure and
      coverage, its financial sources its physical, material and human resources the
      stewardship functions developed by the Ministry of Health the participation of
      citizens in the operation and evaluation of the system and the level of
      satisfaction of health care users. It also discusses the most recent policy
      innovations, including the new General Health Law, the decentralization of the
      regulation of health facilities and the design and implementation of a new health
      care model known as Family and Community Health Model.

PMID- 21877089
TI  - [The health system of Peru].
AB  - This paper describes the health conditions in Peru and, with greater detail, the
      Peruvian health system, including its structure and coverage, its financial
      sources, its physical, material and human resources, and its stewardship
      functions. It also discusses the activities developed in the information and
      research areas, as well as the participation of citizens in the operation and
      evaluation of the health system. The article concludes with a discussion of the
      most recent innovations, including the Comprehensive Health Insurance, the Health
      Care Enterprises system, the decentralization process and the Local Committees
      for Health Administration. The main challenge confronted by the Peruvian health
      system is the extension of coverage to more than I0% of the population presently
      lacking access to basic health care.

PMID- 21877090
TI  - [The health system of Dominican Republic].
AB  - This paper describes the health conditions in Dominican Republic and the
      characteristics of the Dominican health system, including its structure and
      coverage, its financial sources, the health expenditure, the physical, material
      and human resources available, the stewardship functions developed by the
      Ministry of Public Health and the generation of health information. The
      participation of health care users in the operation and evaluation of the system
      and the most recent policy innovations, including the new General Health Law, the
      new Social Security Law and the Decennial Health Plan are also discussed.

PMID- 21877091
TI  - [The health system of Uruguay].
AB  - This paper describes the Uruguayan health system, including its structure and
      coverage, its financial sources, the level and distribution of its health
      expenditure, the physical, material and human resources available, its
      stewardship functions, the institutions in charge of information and research,
      and the level and type of citizen's participation in the operation and evaluation
      of the system. The most recent policy innovations are also discussed, including
      the creation of the National Comprehensive Health System, the National Health
      Insurance, the National Health Fund and the Comprehensive Health Care Program.
      Finally, the impact of these innovations in health expenditure, fairness of
      health financing, coverage levels and main health indicators is analyzed.

PMID- 21877092
TI  - [The health system of Venezuela].
AB  - This paper describes the Venezuelan health system, including its structure and
      coverage, financial sources, human and material resources and its stewardship
      functions. This system comprises a public and a private sector. The public sector
      includes the Ministry of Popular Power for Health (MS) and several social
      security institutions, salient among them the Venezuelan Institute for Social
      Security (IVSS). The MH is financed with federal, state and county contributions.
      The IVSS is financed with employer, employee and government contributions. These
      two agencies provide services in their own facilities. The private sector
      includes providers offering services on an out-of-pocket basis and private
      insurance companies. The Venezuelan health system is undergoing a process of
      reform since the adoption of the 1999 Constitution which calls for the
      establishment of a national public health system. The reform process is now
      headed by the Barrio Adentro program.

PMID- 21877093
TI  - [3 trends are shaping the face of world health in the 21st century].

PMID- 21877094
TI  - [Presentation. Atlas of the health systems of Latin America].

PMID- 21877095
TI  - [Burden of disease in Latin America].
AB  - OBJECTIVE: To describe the burden of disease studies made in the region, identify
      the main priorities in health from the indicator Disability Adjusted Life Years
      (DALYs). MATERIAL AND METHODS: By the use of DALYs identify the burden of disease
      in the countries in the network. RESULTS: DALYs emphasize the emergency of mental
      disorders, diabetes mellitus in women and the disorders associated with alcohol
      consumption and injuries in men. CONCLUSIONS: Latin America is the region with
      more national studies of burden of disease, using a standardized methodology,
      that allows identifying new health priorities which are pressing to the health
      services; for that reason these results constitute an element to take into
      account in the establishment of public policies in each country.

PMID- 21877096
TI  - [Effective coverage of health interventions in Latin America and the Caribbean:
      metrics for the assessment of health systems performance].
AB  - OBJECTIVE: To measure effective coverage for ll health interventions in Latin
      America including the children's, women's and adult health, as part of program
      evaluation. MATERIAL AND METHODS: Interventions were selected; the definitions
      and calculation methods were harmonized according to the information available to
      ensure comparability between countries. RESULTS: Chile has better indicators of
      crude and effective coverage followed by Mexico and Colombia.There are
      significant gaps between regions, counties or states. CONCLUSIONS: The health
      metric on effective coverage is a sensitive indicator that links three important
      aspects: Coverage of health interventions, use of health services, and access to
      such services. Effective coverage is a good tool to evaluate health programs
      performance, and also provides data of where and to whom the system should
      address national efforts and resources to achieve the purposes and goals set.

PMID- 21877097
TI  - Household catastrophic health expenditures: a comparative analysis of twelve
      Latin American and Caribbean Countries.
AB  - OBJECTIVE: Compare patterns of catastrophic health expenditures in 12 countries
      in Latin America and the Caribbean. MATERIAL AND METHODS: Prevalence of
      catastrophic expenses was estimated uniformly at the household level using
      household surveys. Two types of prevalence indicators were used based on out-of
      pocket health expense: a) relative to an international poverty line, and b)
      relative to the household's ability to pay net of their food basket. Ratios of
      catastrophic expenditures were estimated across subgroups defined by economic and
      social variables. RESULTS: The percent of households with catastrophic health
      expenditures ranged from 1 to 25% in the twelve countries. In general, rural
      residence, lowest quintile of income, presence of older adults, and lack of
      health insurance in the household are associated with higher propensity of
      catastrophic health expenditures. However, there is vast heterogeneity by
      country. CONCLUSIONS: Cross national studies may serve to examine how health
      systems contribute to the social protection of Latin American households.

PMID- 21877098
TI  - [The health system of Argentina].
AB  - This paper describes the health system of Argentina.This system has three
      sectors: public, social security and private.The public sector includes the
      national and provincial ministries as well as the network of public hospitals and
      primary health care units which provide care to the poor and uninsured
      population. This sector is financed with taxes and payments made by social
      security beneficiaries that use public health care facilities. The social
      security sector or Obras Sociales (OS) covers all workers of the formal economy
      and their families. Most OS operate through contracts with private providers and
      are financed with payroll contributions of employers and employees. Finally, the
      private sector includes all those private providers offering services to
      individuals, OS beneficiaries and all those with private health insurance.This
      sector also includes private insurance agencies called Prepaid Medicine
      Enterprises, financed mostly through premiums paid by families and/or
      employers.This paper also discusses some of the recent innovations implemented in
      Argentina, including the program Remediar.

PMID- 21877099
TI  - Sensitization and chronic beryllium disease at a primary manufacturing facility,
      part 3: exposure-response among short-term workers.
AB  - OBJECTIVES: Exposure-response relations for beryllium sensitization (BeS) and
      chronic beryllium disease (CBD) using aerosol mass concentration have been
      inconsistent, although process-related risks found in most studies suggest that
      exposure-dependent risks exist. We examined exposure-response relations using
      personal exposure estimates in a beryllium worker cohort with limited work tenure
      to minimize exposure misclassification. METHODS: The population comprised workers
      employed in 1999 with six years or less tenure. Each completed a work history
      questionnaire and was evaluated for immunological sensitization and CBD. A job
      exposure matrix was combined with work histories to create individual estimates
      of average, cumulative, and highest-job-worked exposure for total, respirable,
      and submicron beryllium mass concentrations. We obtained odds ratios from
      logistic regression models for exposure-response relations, and evaluated process
      related risks. RESULTS: Participation was 90.7% (264/291 eligible). Sensitization
      prevalence was 9.8% (26/264), with 6 sensitized also diagnosed with CBD (2.3%,
      6/264). A general pattern of increasing sensitization prevalence was observed as
      exposure quartile increased. Both total and respirable beryllium mass
      concentration estimates were positively associated with sensitization (average
      and highest job), and CBD (cumulative). Increased sensitization prevalence was
      identified in metal/oxide production, alloy melting and casting, and maintenance,
      and for CBD in melting and casting. Lower sensitization prevalence was observed
      in plant-area administrative work. CONCLUSIONS: Sensitization was associated with
      average and highest job exposures, and CBD was associated with cumulative
      exposure. Both total and respirable mass concentrations were relevant predictors
      of risk. New process-related risks were identified in melting and casting and
      maintenance.

PMID- 21877100
TI  - Structure and stability of the molybdenum cofactor intermediate cyclic
      pyranopterin monophosphate.
AB  - Hydrogenated (reduced) pterins are found in all living organisms, where they are
      involved in key metabolic processes. Molybdenum in its biologically active form
      is bound to a fully reduced tetrahydropyranopterin referred to as a metal-binding
      pterin (MPT), forming the so-called molybdenum cofactor (Moco). Cyclic
      pyranopterin monophosphate (cPMP) is the first isolatable intermediate in
      molybdenum cofactor biosynthesis. Here we present for the first time a (13)C NMR
      characterization of an active Moco intermediate. The (13)C NMR data for cPMP
      corroborate previous data showing the tetrahydropyranopterin nature of cPMP and
      the presence of a gem-diol in the C1' position of the side chain. The stability
      of the gem-diol, together with the absence of any observable signal at low field
      (175-220 ppm), is an indication that the gem-diol is not a chemical artifact, but
      is chemically stable and not in equilibrium with the keto form. Finally, we have
      studied spectrophotometrically the kinetics of cPMP oxidation in the presence of
      metal centers, chelating agents, and different buffers and pH values. We found
      that oxidation is metal-dependent and can be substantially retarded in the
      presence of EDTA.

PMID- 21877101
TI  - To know or not to know: influence of explicit advance knowledge of occlusion on
      interceptive actions.
AB  - This study examined how explicit advance knowledge might influence adaptive
      behavior to visual occlusions. Catching performance and kinematics of good ball
      catchers were compared between no, early and late occlusion trials. Discrete
      visual occlusions of 400 ms, occurring early or late in the ball's approach
      trajectory, were randomly interspersed between no occlusion trials. In one
      condition, the presence and type of occlusion were announced a priori (expected),
      whereas in another condition no such information was provided (unexpected).
      Expectation of occlusion resulted in an adapted limb transport and increased
      grasping time, whereas in the unexpected condition a higher peak of wrist
      velocity was evident for all occlusion conditions. The observed different
      adaptations cannot be explained by trial-by-trial adaptations alone and instead
      provide evidence for the influence of explicit advance knowledge in the motor
      response of interceptive actions.

PMID- 21877103
TI  - Manipulations of the relationship between response alternatives and exogenous
      saccade latencies.
AB  - The relationship between the latencies of saccadic eye movements and the number
      of response alternatives is complex. Previously, we have found a decrease in
      exogenous saccade latencies with an increase in the number of response
      alternatives (i.e., an anti-Hick's effect). In the present study, we examined the
      effect of bottom up and top down influences on the effect. In Experiment 1, we
      found that the anti-Hick's effect is dependent upon the number, as opposed to the
      configuration, of response alternatives, suggesting that the effect is not a
      purely bottom up phenomenon. In Experiment 2, we examined whether top down
      processes, such as expectancy, influence the magnitude and/or direction of the
      relationship between response alternatives and reaction time. We found that
      interleaving, as opposed to blocking, the number of alternatives negated the anti
      Hick's effect. Taken together, these results suggest that the anti-Hick's effect
      arises not only from stimulus-based perceptual signals but also from higher-order
      control signals.

PMID- 21877102
TI  - Dyskinetic Parkinson's disease patients demonstrate motor abnormalities off
      medication.
AB  - The pathophysiology of L-dopa-induced dyskinesias (LIDs) in Parkinson's disease
      (PD) remains poorly understood. The presence of superimposed LIDs clearly
      differentiates motor performance of dyskinetic from non-dyskinetic PD subjects
      when they are on medication, but here, we investigated whether their respective
      motor performance differs while subjects are off L-dopa medication and LIDs are
      not apparent. We assessed the motor performance of nine dyskinetic and ten non
      dyskinetic PD subjects off L-dopa, and of ten age-matched control subjects,
      during a visually guided tracking task. As previous studies have suggested that
      linear dynamical system (LDS) models are useful to assess motor performance in PD
      in addition to overall tracking error, we used LDS models to assess the damping
      ratio parameter of motor behavior while controlling for disease severity. While
      overall tracking error did not significantly differ across groups, dyskinetic PD
      subjects demonstrated a significantly decreased mean damping ratio compared with
      control and non-dyskinetic PD subjects. For both groups, greater disease severity
      significantly predicted a lower damping ratio, but even after controlling for
      disease severity, the damping ratio for dyskinetic subjects was significantly
      lower. Our results demonstrate, somewhat counter-intuitively, that motor
      performance of dyskinetic and non-dyskinetic PD subjects differ, even off L-dopa
      when no dyskinesias are seen. A decreased damping ratio is indicative of a
      tendency to overshoot a target during motor performance, similar to the dysmetria
      found in cerebellar patients. We discuss the possibility of motor abnormalities
      in dyskinetic PD patients off medication in relation to altered functional
      cerebellar changes described in PD.

PMID- 21877104
TI  - Preventable hospitalizations: does rurality or non-physician clinician supply
      matter?
AB  - This study examines the relationship between rurality as well as the proportion
      of non-physician clinicians and county rates of ambulatory care sensitive
      hospitalizations (ACSHs) for pediatric, adult and elderly populations in
      Nebraska. The study design was a cross-sectional observational study of county
      level factors that affect the county level rates of ACSHs using Poisson
      regression models. Rural (non-metro) counties have significantly higher ACSHs for
      both pediatric and adult population, but not for the elderly. Frontier counties
      have significantly higher adult ACSHs. The proportion of primary care providers
      who are non-physician clinicians does not have a significant association with
      ACSHs for any of the age groups. The results indicate that rurality may have a
      greater impact on pediatric and adult ACSHs and the proportion of NPCs in the
      primary care provider workforce does not significantly impact ACSH rates.

PMID- 21877105
TI  - Acute myocardial infarction in New York State: 1996-2008.
AB  - We examined the Acute Myocardial Infarction (AMI) incidence and mortality rates
      in New York State for a recent 13-year period. Hospital discharge data and death
      certificate information are combined to create patient episodes for AMI. Trends
      in the risk-adjusted AMI incidence and mortality are examined for the years 1996
      through 2008. Between 1996 and 2008, the AMI incidence rate declined by 35.8% and
      AMI mortality fell from 161.0 to 71.6 per 100,000 population. This 55.5% decline
      in mortality is accompanied by a 23.9% decline in the number of AMI admissions to
      acute care hospitals and by a 37.8% improvement in mortality among those
      hospitalized. New York State follows the national trend in decline in AMI. That
      decline is accompanied by reductions in AMI mortality, reduced demand on
      hospitals, and significant improvement in hospital care quality among AMI
      patients.

PMID- 21877106
TI  - Acute coronary syndrome: factors affecting time to arrival in a diverse urban
      setting.
AB  - This study seeks to better understand how individuals of different
      cultural/ethnic backgrounds in an urban setting assess the signs and symptoms of
      Acute Coronary Syndrome (ACS) and the ensuing decision to take urgent action. Few
      studies exist which examine these differences and enhance understanding of how to
      address these differences and, ultimately, reduce morbidity and mortality from
      ACS. Face-to-face interviews were conducted with a convenience sample of urban
      patients of different cultural and socioeconomic backgrounds regarding their
      actions upon recognition of ACS signs and symptoms. Patients (423) with presumed
      or diagnosed ACS were interviewed within 12 h of arrival at the urban emergency
      rooms. Among the different cultural groups, Haitians delayed the longest (median)
      from symptom onset to hospital arrival (8.24 h), followed by Caribbeans (7.83 h),
      African Americans (6.62 h) and Hispanics (6.00 h). Although these delay intervals
      were not statistically significant across groups, each racial/ethnic group sought
      care well beyond the recommended time period of 3 h after initial recognition of
      ACS signs and symptoms. Among all the cultural groups, the two key factors
      motivating early arrival were being employed and taking positive actions. ACS
      symptom perception by different cultural groups appears to play an important role
      in the decision to seek emergency treatment. This is an area that has not been
      widely studied among or within different cultural/ethnic groups. As such, further
      research is needed to delineate these concepts and actions and to provide
      opportunities for appropriate education.

PMID- 21877107
TI  - Acute myocardial infarction mortality before and after state-wide smoking bans.
AB  - Rapid declines in hospital admissions for acute myocardial infarction (AMI)
      following smoke-free ordinances have been reported in smaller communities. The
      AMI mortality rate among persons age 45 + years (deaths per 100,000 persons, age
      standardized to the 2000 US population) in the 3 years before adoption of the
      smoke-free ordinance (the expected rate) was compared with the rate observed in
      the first full year after the ban (the target year) in six US states. Target-year
      declines were also compared to those in states without smoking bans. Target-year
      declines in AMI mortality in California (2.0%), Utah (7.7%) and Delaware (8.1%)
      were not significantly different from the expected declines (P = 0.16, 0.43 and
      0.89, respectively). In South Dakota AMI mortality increased 8.9% in the target
      year (P = 0.007). Both a 9% decline in Florida and a 12% decline in New York in
      the 2004 target year exceeded the expected declines (P = 0.04 and P < 0.0002,
      respectively) but were not significantly different (P = 0.55 and 0.08,
      respectively) from the 9.8% decline that year in the 44 states without bans.
      Smoke-free ordinances provide a healthy indoor environment, but their
      implementation in six states had little or no immediate measurable effect on AMI
      mortality.

PMID- 21877108
TI  - The New York State optometry workforce study.
AB  - This study presents an analysis of the current optometry workforce, both as a
      unique profession and more broadly within the context of all eye care providers
      (optometry and ophthalmology) in New York State. The supply and distribution of
      eye care practitioners provides useful information for policy makers while
      providing insights as to the impact of the one optometry school within the state.
      Several databases were employed and a web based survey was developed for
      completion by all optometrists. The questionnaire included demographic data,
      whether they were actively practicing in New York State or any other state, were
      they full time or part time, their primary mode of practice, or if they provided
      care within institutional settings. Access to care was gauged by the respondents'
      availability for appointments during evenings or weekends. Access to eye care
      services in New York State has improved significantly during the past 30 years as
      the supply of optometrists increased. Before this study was conducted it was
      generally believed that there were more optometrists than ophthalmologists in
      every state of the nation except New York, Maryland and the District of Columbia.
      Findings of this study demonstrate there are 37% more optometrists in New York
      State than ophthalmologists and more evenly distributed as optometrists are
      located in almost every county of the state. Sixteen counties have no
      ophthalmologists. This is attributed to the presence of the College of Optometry
      established in 1971. More than 60% of all optometrists in the state are SUNY
      College of Optometry graduates.

PMID- 21877109
TI  - Risk factors for liver disease and associated knowledge and practices among
      Mexican adults in the US and Mexico.
AB  - Latinos in the US are disproportionately affected by chronic liver disease, which
      is the sixth most common cause of death among this group. In Mexico, cirrhosis
      and other liver diseases are the fourth leading cause of general mortality. The
      objective of this study was to contrast the liver disease risk factors,
      knowledge, and prevention practices reported among separate samples of Mexicans
      living in Los Angeles, CA and in Cuernavaca, Mexico. We assessed the prevalence
      of specific risk factors (body mass index, waist circumference, and alcohol
      consumption), the level of knowledge about liver disease in general, hepatitis B
      (HBV), and hepatitis C (HCV), as well as prevention activities such as screening
      and vaccination. Data were collected from in-person interviews and anthropometric
      measures obtained from Mexican adults aged 18-70 years. Chi-square and t tests
      were used to compare the results between groups. Numerous similarities were
      observed in the bi-national samples, including high prevalence of obesity,
      abdominal obesity, and high levels of alcohol consumption. Most participants in
      both countries recognized that excessive alcohol consumption is a risk factor for
      liver disease, but only 60% correctly identified hepatitis C, being overweight or
      obese, or having diabetes as risk factors. Few participants reported having been
      screened for HBV or HCV, vaccinated for HBV, or having the intention of getting
      screened for HBV or HCV. US participants reported significantly higher levels of
      prevention activities and screening intentions than those in Mexico. Identifying
      the specific risk factors, levels of knowledge and prevention activities that
      affect specific racial/ethnic populations is important in order to effectively
      target efforts to prevent liver disease.

PMID- 21877110
TI  - Cardiovascular disease risk factors and diabetes in Asian Indians residing in
      Michigan.
AB  - Asian Indians are the largest Asian subgroup in the state of Michigan; however,
      data on the prevalence and correlates of cardiovascular disease for this group is
      limited. The sample consisted of 273 Asian Indians (AI) recruited through health
      fairs for surveys and blood tests throughout the state of Michigan. The
      prevalence of self-reported diabetes (20.1%) and elevated/abnormal glycated
      hemoglobin A1C levels (22.6%) exceeds the percentages of other ethnic groups
      reported in 2006-2008 Michigan Behavioral Risk Factor Survey. More than half of
      respondents had elevated body max index. The gender disparity in hypertension
      prevalence (50% for males vs. 19.3% for females) has not been observed in other
      similar studies and prevalence of male participants with hypertension also is
      higher than reported in other studies. In the multivariate analysis after
      adjusting demographic and access to health care factors, the results showed that
      the prevalence of metabolic syndrome increases among AI female participants but
      not among AI males. The data highlight the need for developing culturally
      tailored interventions to effectively reduce multiple risk factors in this group.

PMID- 21877111
TI  - Osteonecrosis of the humeral head.

PMID- 21877112
TI  - Attractive tools for systematic case accumulation.

PMID- 21877113
TI  - Anaplastic large cell lymphoma of the esophagus in a pediatric patient.
AB  - We report a 3-year-old boy who initially presented with abdominal pain and was
      subsequently found to have an esophageal perforation. The child did not respond
      to conservative management, and subsequent lymphadenopathy led to a lymph node
      biopsy demonstrating an anaplastic lymphoma kinase (ALK)+ anaplastic large cell
      lymphoma. Esophageal perforation and thickening is most commonly seen in children
      with a history of esophageal intervention or foreign body/caustic ingestion.
      Esophageal involvement in children with non-Hodgkin lymphoma (NHL) has not, to
      our knowledge, been reported in the literature. This case illustrates an unusual
      presentation of pediatric NHL.

PMID- 21877114
TI  - Regarding online publication of 'CT appearance of the duodenum and mesenteric
      vessels in children with normal and abnormal bowel rotation'.

PMID- 21877115
TI  - Improved MRI of the neonatal heart: feasibility study using a knee coil.
AB  - As a first step towards the development of a neonatal cardiac MRI (CMRI) coil, we
      investigated the utilization, handling and image quality of a knee coil for CMRI
      in infants at 3 Tesla. Scout imaging and cine imaging with optimized pulse
      sequence parameters were performed in two neonates and the resulting images were
      evaluated for diagnostic purposes. All images were of high diagnostic quality.
      Complete examinations took less than five minutes. The excellent signal-to-noise
      ratio provided by this coil allowed all cine studies to be acquired with only
      three averages. In conclusion, a knee coil can be successfully applied in
      neonates for CMRI, but the coil design could be improved further to facilitate
      routine clinical use.

PMID- 21877116
TI  - Fracture after bisphosphonate treatment in children with cerebral palsy: the role
      of stress risers.
AB  - BACKGROUND: In the nonambulatory cerebral palsy (CP) population with a prior
      history of fracture, the use of pamidronate is not always effective in preventing
      further fractures. OBJECTIVE: To test the hypothesis that when fractures occur
      after cyclic pamidronate, they will be at the proximal or distal end of a
      pamidronate band. MATERIALS AND METHODS: Retrospective review of our CP patient
      database revealed 53 children who had received one or more complete courses of
      pamidronate therapy (five cycles over 12 months). Medical records were screened
      to identify children who had sustained a fracture or fractures after completing
      treatment. RESULTS: Of 53 patients treated with pamidronate, only 14 sustained
      fractures after treatment. Radiographs were available for 11 patients, showing 19
      fractures. Sixty-three percent of these fractures were located at a junction with
      pamidronate bands but not within the bands. CONCLUSIONS: We propose stress risers
      as the mechanism for fractures that have occurred where bone mineral density
      abruptly changes as a result of cyclic administration of pamidronate. We show a
      theoretical example of how alternative dosing might reduce the ratio and
      therefore decrease the chance of formation of a stress riser.

PMID- 21877117
TI  - Impact of interactions between normal and transformed epithelial cells and the
      relevance to cancer.
AB  - The majority of human cancers are initiated when a single cell in an epithelial
      sheet becomes transformed. Cell transformation arises from the activation of
      oncoproteins and/or inactivation of tumor suppressor proteins. Recent studies
      have independently revealed that interaction and communication between
      transformed cells and their normal neighbors have a significant impact on the
      fate of the transformed cell. Several reports have shown that various phenomena
      occur at the interface between normal and transformed epithelial cells following
      the initial transformation event. In epithelia of Drosophila melanogaster,
      transformed and normal cells compete for survival in a process termed cell
      competition. This review will summarize current research and discuss the impact
      of these studies on our understanding of how primary tumors emerge and develop
      within a normal epithelium.

PMID- 21877118
TI  - Spectrin-based skeleton as an actor in cell signaling.
AB  - This review focuses on the recent advances in functions of spectrins in non
      erythroid cells. We discuss new data concerning the commonly known role of the
      spectrin-based skeleton in control of membrane organization, stability and shape,
      and tethering protein mosaics to the cellular motors and to all major filament
      systems. Particular effort has been undertaken to highlight recent advances
      linking spectrin to cell signaling phenomena and its participation in signal
      transduction pathways in many cell types.

PMID- 21877119
TI  - B7-H6/NKp30 interaction: a mechanism of alerting NK cells against tumors.
AB  - Natural killer (NK) cells are lymphocytes of the innate immune system that sense
      target cells through a panel of activating and inhibitory receptors. Together
      with NKG2D, the natural cytotoxicity receptors (NCRs) are major activating
      receptors involved in tumor cell detection. Although numerous NKG2D ligands have
      been identified, characterization of the molecules interacting with the NCRs is
      still incomplete. The identification of B7-H6 as a counter structure of the NCR
      NKp30 shed light on the molecular basis of NK cell immunosurveillance. We review
      here the current knowledge on NKp30 and B7-H6, and we discuss their potential
      role in anti-tumor immunity.

PMID- 21877120
TI  - Variability in CKD stage in outpatients followed in two large renal clinics:
      implications for CKD trials and the status of current knowledge of patterns of
      CKD to ESRD progression.

PMID- 21877121
TI  - Social and clinical predictors of prostate cancer treatment decisions among men
      in South Carolina.
AB  - OBJECTIVE: To assess social and clinical influences of prostate cancer treatment
      decisions among white and black men in the Midlands of South Carolina. METHODS:
      We linked data collected on treatment decision making in men diagnosed with
      prostate cancer from 1996 through 2002 with clinical and sociodemographic factors
      collected routinely by the South Carolina Central Cancer Registry (SCCCR).
      Unconditional logistic regression was used to assess social and clinical
      influences on treatment decision. RESULTS: A total of 435 men were evaluated. Men
      of both races who chose surgery (versus radiation) were more likely to be
      influenced by their physician and by family/friends. Black men who chose surgery
      also were ~5 times more likely to make independent decisions (i.e., rather than
      be influenced by their doctor). White men who chose surgery were twice as likely
      to be influenced by the desire for cure and less likely to consider the side
      effects of impotence (odds ratio (OR) = 0.40; 95% confidence interval (CI): 0.18,
      0.88) and incontinence (OR = 0.27; 95% CI: 0.12, 0.63); by contrast, there was a
      suggestion of an opposite effect in black men, whose decision regarding surgery
      tended to be more strongly influenced by these side effects. CONCLUSION: Results
      suggest that both clinical and social predictors play an important role for men
      in choosing a prostate cancer treatment, but these influences may differ by race.

PMID- 21877122
TI  - Regular aspirin use and breast cancer risk in US Black women.
AB  - BACKGROUND: Epidemiologic studies have yet to provide consistent evidence to
      support a protective effect of aspirin and other non-steroidal anti-inflammatory
      drugs (NSAID) on the incidence of breast cancer. OBJECTIVE: We evaluated the
      relations of current use of aspirin, non-aspirin NSAIDs, and acetaminophen with
      breast cancer incidence in the Black Women's Health Study. METHODS: Biennial
      follow-up of 59,000 study participants began in 1995. During 558,600 person-years
      of follow-up through 2007, 1,275 breast cancer cases were identified. Using Cox
      proportional hazards regression, we estimated incidence rate ratios (IRR) and 95%
      confidence intervals (CI) for associations of current and former use of aspirin,
      other NSAIDs, and acetaminophen with incident breast cancer. RESULTS: After
      adjustment for age, education, body mass index at age 18, physical activity,
      female hormone use, current smoking, and other NSAID use, the IRRs were 0.79 (95%
      CI = 0.66, 0.95) for current aspirin use and 0.68 (95% CI = 0.50, 0.92) for >=5
      years of aspirin use. Similar associations were observed for acetaminophen use.
      CONCLUSIONS: Both aspirin and acetaminophen use were inversely associated with
      breast cancer incidence in the present study. Reasons for the association with
      acetaminophen use are unclear, given that acetaminophen has very weak anti
      inflammatory effects.

PMID- 21877123
TI  - A note on the evaluation of BoNTA trial quality.
AB  - In their systematic review, Zhang et al. evaluate randomized controlled trials on
      the efficacy of Botulinum toxin type A (BoNTA) in helping patients with
      musculoskeletal disorders. Scoring each trial according to the Jadad scale they
      note that the studies range from 1 to 5 with an average of 4.1, which they
      interpret as a testimony of the high quality of the studies included.
      Unfortunately, we cannot share the author's enthusiasm, as a perfect Jadad score
      of 5 is no guarantee that a study is of good quality.

PMID- 21877124
TI  - The newly-recognized species Staphylococcus massiliensis is likely to be part of
      the human skin microflora.
AB  - Staphylococcus massiliensis is a newly-recognized species but its ecological
      niche and its role in infection remained unclear. Clinical isolate WCG21
      recovered from a wound sample was initially identified as Staphylococcus simulans
      by the WalkAway automated system but was subsequently identified as S.
      massiliensis by partially sequencing the 16S rRNA and dnaJ genes. Strain WCG21
      was probably a contaminant rather than a pathogen. The 16S rRNA gene sequences of
      several bacterial clones from human skin were also identical or near identical to
      that of S. massiliensis, suggesting that this species is part of human skin
      microflora. Although strain WCG21 was susceptible to a wide range of
      antimicrobials, it harbored a type V staphylococcal cassette chromosome mec.

PMID- 21877125
TI  - Acute kidney injury caused by consumption of melamine-contaminated infant formula
      in 47 children: a multi-institutional experience in diagnosis, treatment and
      follow-up.
AB  - Since the spring of 2008, an epidemic of urinary tract stones was noted among
      children in China. This is believed to be associated with consumption melamine
      contaminated powdered formula. A few patients presented with acute kidney injury
      (AKI) due to bilateral renal or ureteral calculi requiring surgical intervention
      to relieve the obstruction. We retrospectively analyzed clinical and laboratory
      data, ultrasonograms and treatment methods in children with melamine-induced
      urolithiasis and AKI who were hospitalized at seven hospitals from September to
      November 2008 in Gansu Province, China. Treatment given included conservative
      treatment, cystoscopic or urethroscopic lithotripsy, retrograde ureteral
      catheterization, ureterolithotomy and nephrostomy. Patients were monitored
      postoperatively with data of ultrasonography, urinalysis and blood and urine
      biochemistry. The mean age of the 47 children was 10 months (mean +/- SD, 10.83
      +/- 5.11 months). Thirty-four (72.34%) were male. Calculi size ranged from 3 to
      14 mm in diameter. Nine patients (19.15%) were successfully treated with
      conservative treatment; 32 (68.09%) underwent retrograde ureteral catheterization
      and eight had simultaneous cystoscopic or urethroscopic stone removal; four were
      successfully treated with ureterolithotomy, and 1 underwent percutaneous
      nephrostomy. Thirty-eight patients were followed up for a mean +/- SD of 18.50 +/
      5.27 months and their renal functions were found to have completely recovered.
      Five (13.16%) cases had residual renal stones with diameter ranging from 2 to 4
      mm. Therefore, this study has demonstrated that melamine-induced urolithiasis
      could lead to AKI. Removing obstruction promptly by surgical intervention has
      been found to be effective with satisfactory outcomes observed at mean follow-up
      period of 18-month. However, residual renal stone remained in 13.16% of the cases
      which required continued close observation.

PMID- 21877126
TI  - Octenidine in combination with polymethylmethacrylate: a new option for
      preventing infection?
AB  - BACKGROUND: Orthopedic implant infections represent a serious complication for
      both patient and surgeon. In order to minimize this risk, it has become standard
      practice in surgery and orthopedics to add antimicrobial substances to the
      polymethylmethacrylate (PMMA) bone cement. The aim of this study is to find new
      options for preventing infection by using alternative adjuvants in combination
      with PMMA. We hypothesized, that Octenidine, after being combined with PMMA, can
      be released in vitro and an antimicrobial efficacy of discharged Octenidine can
      be shown. METHODS: The release of Octenidine from PMMA was assessed in high
      pressure liquid chromatography of the supernatant. In order to assess the
      efficacy of Octenidine on Staphylococcus aureus and Pseudomonas aeruginosa in
      vitro, a nutrient solution for these bacteria was incubated with a defined number
      of these bacteria (10(6) colony forming units) and cement pellets containing the
      antiseptic Octenidine for 24 h. After the incubation the number of bacteria in
      the solution was determined by counting the colony forming units on blood agar
      plates. RESULTS: Octenidine was shown to be released in a concentration-dependent
      manner from PMMA in the elution experiment. The experimental procedure using S.
      aureus demonstrated a bactericidal effect for bone cement containing Octenidine.
      For P. aeruginosa, bone cement containing 5-8% Octenidine was associated with
      tenfold reduction in bacterial count. CONCLUSION: These results suggest that
      Octenidine is released after combining it with PMMA and reaches working
      concentrations in vitro. These findings suggest a new and effective alternative
      for prevention of infection in cemented implants. Further investigations on the
      biocompatibility of this combination is needed.

PMID- 21877127
TI  - Angle stable locking nails versus conventionally locked intramedullary nails in
      proximal tibial shaft fractures: a biomechanical study.
AB  - INTRODUCTION: A tibial nail with fixed-angle locking screws intends to combine
      the advantages of angular stability and intramedullary stabilization in
      extraarticular proximal tibial fractures. The goal of this study is to analyze if
      the angle stable tibial nail (ASN) is biomechanically more stable than an
      established conventional standard nail (CN). METHODS: Two types of nails were
      compared on a series of ten matched pairs of human tibiae. After setting a
      proximal tibial defect fracture, the intramedullary stabilized tibiae were
      axially loaded starting from 100 N increasing in steps of 100 N after every 200
      cycles until failure was reached. Failure was defined as deformation of the
      fracture gap, fracturing of the bone or the implant. RESULTS: The two types of
      nails showed no significant difference in terms of maximum tolerated load,
      maximum cycles repeated or axial deformation of the bone-implant construct. The
      mean load at failure was 1,365 N for the CN and 1,195 N for the ASN. The mean
      axial deformation for conventional (19 mm) and angle stable nail (21 mm) did not
      differ significantly. Slightly less nail or screw loosening was noticed with the
      fixed-angle nail. CONCLUSION: No significant difference in stability between the
      two compared implants could be demonstrated. A trend could be shown indicating
      that the rate of nail loosening in the proximal osteotomized part of the bone was
      lower for the angle stable nail. This trend, however, could not be substantiated
      statistically.

PMID- 21877129
TI  - Platelet-rich plasma in mono-segmental posterior lumbar interbody fusion: a novel
      molecular mechanism.

PMID- 21877130
TI  - Remodeling of adjacent spinal alignments following cervical arthroplasty and
      anterior discectomy and fusion.
AB  - OBJECTIVE: To evaluate the effects of cervical artificial disc replacement (ADR)
      and anterior discectomy and fusion (ACDF) on adjacent spinal alignments. METHODS:
      The cohort consisted of 33 patients who undergone single-level cervical ADR (15
      patients) and ACDF (18 patients) for radiculopathy, who had not had any previous
      spine surgery, and who had a minimum follow-up of 2 years. Whole-spine lateral
      radiographs were taken at the pre-operative and follow-up consultations. Cervical
      lordosis, thoracic kyphosis, lumbar lordosis, and sagittal balance were measured
      each time. The patients filled out pre-operative and follow-up functional
      evaluation forms including visual analogue scale (VAS) of neck and arm. The mean
      follow-up durations of patients who had cervical ADR and ACDF were 28 +/- 5.0 and
      30 +/- 5.8 months, respectively. The patients having ACDF had the higher mean age
      (53 +/- 9.0 years) than that of patients with cervical ADR (45 +/- 11.7 years).
      RESULTS: The cervical lordosis and thoracic kyphosis in cervical ADR group
      increased significantly more than those of the ACDF group in follow-up assessment
      (P = 0.011 and 0.012). There was no significant change of lumbar lordosis in
      intra- and inter-group analyses. The follow-up sagittal balances for the cervical
      ADR and ACDF groups moved towards a neutral value. Although the follow-up neck
      and arm VAS of the both groups improved than those of the pre-operative status,
      the groups did not differ significantly except for a difference in neck VAS,
      which improved more after ADR. CONCLUSIONS: The remodeling of cervical and
      thoracic curves after cervical ADR and ACDF was coupled and complementary.
      Cervical ADR contributed the restorations of angulations of cervical and thoracic
      spines. The neck VAS improved more after cervical ADR than after ACDF.

PMID- 21877128
TI  - Molecular aspects of flower development in grasses.
AB  - The grass family (Poaceae) of the monocotyledons includes about 10,000 species
      and represents one of the most important taxa among angiosperms. Their flower
      morphology is remarkably different from those of other monocotyledons and higher
      eudicots. The peculiar floral structure of grasses is the floret, which contains
      carpels and stamens, like eudicots, but lacks petals and sepals. The reproductive
      organs are surrounded by two lodicules, which correspond to eudicot petals, and
      by a palea and lemma, whose correspondence to eudicot organs remains
      controversial. The molecular and genetic analysis of floral morphogenesis and
      organ specification, primarily performed in eudicot model species, led to the
      ABCDE model of flower development. Several genes required for floral development
      in grasses correspond to class A, B, C, D, and E genes of eudicots, but others
      appear to have unique and diversified functions. In this paper, we outline the
      present knowledge on the evolution and diversification of grass genes encoding
      MIKC-type MADS-box transcription factors, based on information derived from
      studies in rice, maize, and wheat. Moreover, we review recent advances in
      studying the genes involved in the control of flower development and the extent
      of structural and functional conservation of these genes between grasses and
      eudicots.

PMID- 21877131
TI  - Safety, effectiveness and predictors for early reoperation in therapeutic and
      prophylactic vertebroplasty: short-term results of a prospective case series of
      patients with osteoporotic vertebral fractures.
AB  - INTRODUCTION: Vertebroplasty (VP) is a cost-efficient alternative to kyphoplasty;
      however, regarding safety and vertebral body (VB) height restoration, it is
      considered inferior. We assessed the safety and efficacy of VP in alleviating
      pain, improving quality of life (QoL) and restoring alignment. METHODS: In a
      prospective monocenter case series from May 2007 until July 2008, there were
      1,408 vertebroplasties performed during 319 interventions in 306 patients with
      traumatic, lytic and osteoporotic fractures. The 249 interventions in 233
      patients performed because of osteoporotic vertebral fractures were analyzed
      regarding demographics, treatment and radiographic details, pain alleviation
      (VAS), QoL improvement (NASS and EQ-5D), complications and predictors for new
      fractures requiring a reoperation. RESULTS: The osteoporotic patient sample
      consisted of 76.7% (179) females with a median age of 80 years. A total of 54
      males had a median age of 77 years. On average, there were 1.8 VBs fractured and
      5 VBs treated. The preoperative pain was assessed by the visual analog scale
      (VAS) and decreased from 54.9 to 40.4 pts after 2 months and 31.2 pts after 6
      months. Accordingly, the QoL on the EQ-5D measure (-0.6 to 1) improved from 0.35
      pts before surgery to 0.56 pts after 2 and to 0.68 pts after 6 months. The
      preoperative Beck Index (anterior height/posterior height) improved from a mean
      of 0.64 preoperative to 0.76 postoperative, remained stable at 2 months and
      slightly deteriorated to 0.72 at 6 months postoperatively. There were cement
      leakages in 26% of the fractured VBs and in 1.4% of the prophylactically cemented
      VBs; there were symptoms in 4.3%, and most of them were temporary hypotension and
      one pulmonary cement embolism that remained asymptomatic. The univariate
      regression model revealed a tendency for a reduced risk for new or refractures on
      radiographs (OR = 2.61, 95% CI 0.92-7.38, p = 0.12) and reoperations (OR = 2.9,
      95% CI 0.94-8.949, p = 0.1) when prophylactic augmentation was performed. The
      final multivariate regression model revealed male patients to have an about three
      times higher refracture risk (radiographic) (OR = 2.78, p = 0.02) at 6 months
      after surgery. Patients with a lumbar index fracture had an about three to five
      times higher refracture/reoperation risk than patients with a thoracic (OR =
      0.33/0.35, p = 0.009/0.01) or thoracolumbar (OR = 0.32/0.22, p = 0.099/0.01)
      index fracture. CONCLUSION: If routinely used, VP is a safe and efficacious
      treatment option for osteoporotic vertebral fractures with regard to pain relief
      and improvement of the QoL. Even segmental realignment can be partially achieved
      with proper patient positioning. Certain patient or fracture characteristics
      increase the risk for early radiographic refractures or new fractures, or a
      reoperation; a consequent prophylactic augmentation showed protective tendencies,
      but the study was underpowered for a final conclusion.

PMID- 21877132
TI  - Genetic mapping of an autosomal recessive postaxial polydactyly type A to
      chromosome 13q13.3-q21.2 and screening of the candidate genes.
AB  - Postaxial Polydactyly (PAP) is characterized by fifth digit duplication in hands
      and/or feet. Two types of PAP including PAP-A, representing the development of
      well-formed extra digit, and PAP-B, representing the presence of rudimentary
      fifth digit, have been described. Both isolated and syndromic forms of PAP have
      been reported. Isolated forms of PAP usually segregate as an autosomal dominant
      trait and to date four loci have been identified. In the present study, we have
      described mapping of the first locus of autosomal recessive PAP type A on
      chromosome 13q13.3-13q21.2 in a consanguineous Pakistani family. Using
      polymorphic microsatellite markers, the disease locus was mapped to a 17.87-cM
      (21.13 Mb) region flanked by markers D13S1288 and D13S632, on chromosome 13q13.3
      13q21.2. A maximum multipoint LOD score of 3.84 was obtained with several markers
      along the disease interval. DNA sequence analysis of exons and splice-junction
      sites of ten candidate genes (CHM-I, TSC22D1, FOXO1, DIAPH3, CCDC122, CKAP2,
      SUGT1, RANKL, LPAR6, C13ORF31) did not reveal potentially causal variants.

PMID- 21877133
TI  - Novel Alu retrotransposon insertion leading to Alstrom syndrome.
AB  - Alstrom syndrome is a clinically complex disorder characterized by childhood
      retinal degeneration leading to blindness, sensorineural hearing loss, obesity,
      type 2 diabetes mellitus, cardiomyopathy, systemic fibrosis, and pulmonary,
      hepatic, and renal failure. Alstrom syndrome is caused by recessively inherited
      mutations in the ALMS1 gene, which codes for a putative ciliary protein. Alstrom
      syndrome is characterized by extensive allelic heterogeneity, however, founder
      effects have been observed in some populations. To date, more than 100 causative
      ALMS1 mutations have been identified, mostly frameshift and non-sense alterations
      resulting in termination signals in ALMS1. Here, we report a complex Turkish
      kindred in which sequence analysis uncovered an insertion of a novel 333 basepair
      Alu Ya5 SINE retrotransposon in the ALMS1 coding sequence, a previously
      unrecognized mechanism underlying the mutations causing Alstrom syndrome. It is
      extraordinarily rare to encounter the insertion of an Alu retrotransposon in the
      coding sequence of a gene. The high frequency of the mutant ALMS1 allele in this
      isolated population suggests that this recent retrotransposition event spreads
      quickly, and may be used as a model to study the population dynamics of
      deleterious alleles in isolated communities.

PMID- 21877134
TI  - Expression signature of epidermolysis bullosa simplex.
AB  - Epidermolysis bullosa simplex (EBS) is a skin disorder resulting from a weakened
      cytoskeleton of the proliferative compartment of the epidermis, leading to cell
      fragility and blistering. Although many mutations have been identified in
      intermediate filament keratins KRT5 and KRT14, detailed pathogenic mechanisms and
      the way these mutations affect cell metabolism are unclear. Therefore, we
      performed genomic and transcriptomic study in six Canadian EBS patients and six
      healthy subjects. We first characterized these patients at the genetic level and
      identified six pathogenic mutations of which two were novel. Then, we performed
      an expression microarray analysis of the EBS epidermis tissue to identify
      potential regulatory pathways altered in this disease. Expression profiling
      comparisons show that 28 genes are differentially expressed in EBS patients
      compared to control subjects and 41 genes in severe phenotype patients (EBS-DM)
      compared to their paired controls. Nine genes involved in fatty acid metabolism
      and two genes in epidermal keratinization are common altered expressed genes (up
      regulated) between the two subgroups. These two biological pathways contribute
      both to the formation of the cell envelope barrier and seem to be defective in
      the severe EBS phenotype. This study identifies, for the first time, the fatty
      acid metabolism disruption in EBS.

PMID- 21877136
TI  - A DICOM-based 2nd generation Molecular Imaging Data Grid implementing the IHE XDS
      i integration profile.
AB  - PURPOSE: A Molecular Imaging Data Grid (MIDG) was developed to address current
      informatics challenges in archival, sharing, search, and distribution of
      preclinical imaging studies between animal imaging facilities and investigator
      sites. This manuscript presents a 2nd generation MIDG replacing the Globus
      Toolkit with a new system architecture that implements the IHE XDS-i integration
      profile. Implementation and evaluation were conducted using a 3-site
      interdisciplinary test-bed at the University of Southern California. METHODS: The
      2nd generation MIDG design architecture replaces the initial design's Globus
      Toolkit with dedicated web services and XML-based messaging for dedicated
      management and delivery of multi-modality DICOM imaging datasets. The Cross
      enterprise Document Sharing for Imaging (XDS-i) integration profile from the
      field of enterprise radiology informatics was adopted into the MIDG design
      because streamlined image registration, management, and distribution dataflow are
      likewise needed in preclinical imaging informatics systems as in enterprise PACS
      application. Implementation of the MIDG is demonstrated at the University of
      Southern California Molecular Imaging Center (MIC) and two other sites with
      specified hardware, software, and network bandwidth. RESULTS: Evaluation of the
      MIDG involves data upload, download, and fault-tolerance testing scenarios using
      multi-modality animal imaging datasets collected at the USC Molecular Imaging
      Center. The upload, download, and fault-tolerance tests of the MIDG were
      performed multiple times using 12 collected animal study datasets. Upload and
      download times demonstrated reproducibility and improved real-world performance.
      Fault-tolerance tests showed that automated failover between Grid Node Servers
      has minimal impact on normal download times. CONCLUSIONS: Building upon the 1st
      generation concepts and experiences, the 2nd generation MIDG system improves
      accessibility of disparate animal-model molecular imaging datasets to users
      outside a molecular imaging facility's LAN using a new architecture, dataflow,
      and dedicated DICOM-based management web services. Productivity and efficiency of
      preclinical research for translational sciences investigators has been further
      streamlined for multi-center study data registration, management, and
      distribution.

PMID- 21877137
TI  - Toward locating the source of serotonergic axons in the tail nerve of Aplysia.
AB  - Stimulation of the tail nerve (pedal nerve 9, p9) of the mollusk, Aplysia
      californica, causes release of serotonin (5-HT), which mediates sensitization of
      withdrawal responses. There are about 35 serotonin-immunoreactive (5-HT-ir) axons
      in p9, yet the cell bodies of these axons have not been located. Backfills of p9
      were combined with 5-HT immunohistochemistry to locate the cell bodies of 5-HT-ir
      neurons with axons in p9. About 100 neurons had axons in p9. Only about ten
      neurons, however, were both backfilled and 5-HT-ir. These double-labeled neurons
      were all located in the pedal ganglion associated with p9, which had a total of
      approximately 42 5-HT-ir somata. The discrepancy between the number of 5-HT-ir
      axons and double-labeled cell bodies is not likely due to neurons having multiple
      axons in the nerve; intracellular fills suggest that these neurons do not branch
      before entering p9. Additionally, no evidence was found for peripheral 5-HT-ir
      cell bodies that project axons centrally through p9. Thus, approximately 70% of
      the neurons that give rise to the 5-HT-ir axons in tail nerve are unaccounted
      for, but likely to reside in the pedal ganglion.

PMID- 21877138
TI  - The cost of serially chaining two cognitive operations.
AB  - As Turing (1936, Proceedings of the London Mathematical Society) noted, a
      fundamental process in human cognition is to effect chained sequential operations
      in which the second operation requires an input from the preceding one. Although
      a great deal is known about the costs associated with 'independent' (unrelated)
      operations, e.g., from the classic psychological refractory period paradigm, far
      less is known about those operations to which Turing referred. We present the
      results of two behavioural experiments, where participants were required to
      perform two speeded sequential tasks that were either chained or independent.
      Both experiments reveal the reaction time cost of chaining, over and above
      classical dual-task serial costs. Moreover, the chaining operation significantly
      altered the distribution of reaction times relative to the Independent condition
      in terms of an increased mean and variance. These results are discussed in terms
      of the cognitive architecture underlying the serial chaining of cognitive
      operations.

PMID- 21877135
TI  - The lens in focus: a comparison of lens development in Drosophila and
      vertebrates.
AB  - The evolution of the eye has been a major subject of study dating back centuries.
      The advent of molecular genetics offered the surprising finding that
      morphologically distinct eyes rely on conserved regulatory gene networks for
      their formation. While many of these advances often stemmed from studies of the
      compound eye of the fruit fly, Drosophila melanogaster, and later translated to
      discoveries in vertebrate systems, studies on vertebrate lens development far
      outnumber those in Drosophila. This may be largely historical, since Spemann and
      Mangold's paradigm of tissue induction was discovered in the amphibian lens.
      Recent studies on lens development in Drosophila have begun to define molecular
      commonalities with the vertebrate lens. Here, we provide an overview of
      Drosophila lens development, discussing intrinsic and extrinsic factors
      controlling lens cell specification and differentiation. We then summarize key
      morphological and molecular events in vertebrate lens development, emphasizing
      regulatory factors and networks strongly associated with both systems. Finally,
      we provide a comparative analysis that highlights areas of research that would
      help further clarify the degree of conservation between the formation of dioptric
      systems in invertebrates and vertebrates.

PMID- 21877140
TI  - An unusual form of reaction wood in Koromiko [Hebe salicifolia G. Forst.
      (Pennell)], a southern hemisphere angiosperm.
AB  - Koromiko [Hebe salicifolia G. Forst. (Pennell)] is a woody angiosperm native to
      New Zealand and Chile. Hebe spp. belong to the otherwise herbaceous family
      Plantaginaceae in the order Lamiales. Reaction wood exerting expansional forces
      was found on the lower side of leaning H. salicifolia stems. Such reaction wood
      is atypical for angiosperms, which commonly form contracting reaction wood on the
      upper side of leaning stems. Reaction wood typical for angiosperms is formed by
      species in other families in the order Lamiales. This suggests that the form of
      reaction wood is specific to the family level. Functionally the reaction wood of
      H. salicifolia is similar to that found in gymnosperms, which both act by
      pushing. However, their chemical, anatomical and physical characteristics are
      different. Typical features of reaction wood present in gymnosperms such as high
      density, thick-walled rounded cells and the presence of (1 -> 4)-beta-galactan in
      the secondary cell wall layer are absent in H. salicifolia reaction wood.
      Reaction wood of H. salicifolia varies from normal wood in having a higher
      microfibril angle, which is likely to determine the direction of generated
      maturation stresses.

PMID- 21877139
TI  - High light stimulates Deg1-dependent cleavage of the minor LHCII antenna proteins
      CP26 and CP29 and the PsbS protein in Arabidopsis thaliana.
AB  - The chloroplast Deg1 protein performs proteolytic cleavage of the photodamaged D1
      protein of the photosystem II (PSII) reaction center, PSII extrinsic subunit PsbO
      and the soluble electron carrier plastocyanin. Using biochemical, immunological
      and mass spectrometry approaches we showed that the heterogeneously expressed
      Deg1 protease from Arabidopsis thaliana can be responsible for the degradation of
      the monomeric light-harvesting complex antenna subunits of PSII (LHCII), CP26 and
      CP29, as well as PSII-associated PsbS (CP22/NPQ4) protein. The results may
      indicate that cytochrome b (6) protein and two previously unknown thylakoid
      proteins, Ptac16 and an 18.3-kDa protein, may be the substrates for Deg1. The
      interaction of Deg1 with the PsbS protein and the minor LHCII subunits implies
      its involvement in the regulation of both excess energy dissipation and state
      transition adaptation processes.

PMID- 21877141
TI  - Expressions of individual PHDs associate with good prognostic factors and
      increased proliferation in breast cancer patients.
AB  - Tumor hypoxia-inducible transcription factor (HIF) overexpression often
      associates with a poor prognosis. Stability of the HIF-alpha subunits is
      regulated by HIF prolyl 4-hydroxylases, PHD1-3. We assessed here
      immunohistochemical expression of PHD1-3 and HIF-1alpha and 2alpha in patients
      with invasive ductal breast carcinoma (n = 102) and correlated their expression
      levels with main clinical prognostic factors and survival. PHD1 expression
      correlated with high proliferation, and these tumors were mainly estrogen
      receptor-negative. PHD3 expression declined in tumors of large size, poor
      differentiation, and high proliferation. There was a tendency for increased
      breast cancer-specific survival and longer disease-free survival among patients
      with high tumor PHD2 expression. Surprisingly, PHD1-3 expression did not
      correlate with HIF-1alpha or HIF-2alpha downregulation. However, HIF-2alpha
      expression correlated independently with low tumor stage and HIF-1alpha
      expression had a tendency for decreased breast cancer-specific survival. PHD1 and
      3 appear to be HIF-independent factors in breast cancer. Not all PHD1 associated
      proliferation is estrogen-dependent and it is associated with a poor prognosis of
      cancer. PHD3 may be an important regulator of apoptosis and it is mainly found in
      tumors with good prognosis. PHD2 expression is likely to be involved in increased
      survival.

PMID- 21877143
TI  - Lack of correlation between first trimester maternal serum 25-hydroxyvitamin D
      levels and ultrasound measured crown-rump length and nuchal translucency.
AB  - BACKGROUND: Vitamin D regulates the human genome and it is thought to influence
      the fetal growth and development, but its relation to early ultrasound fetal
      measures is still unknown. OBJECTIVE: To assess first trimester 25-hydroxyvitamin
      D [25(OH)D] maternal serum status and correlate with ultrasound crown-rump length
      (CRL) and nuchal translucency (NT) measurements. METHOD: In this cross-sectional
      study, women with singleton pregnancies undergoing the first trimester standard
      two-dimensional ultrasound scan for fetal anomalies were included: CRL (n = 498)
      and NT (n = 487). Concomitantly, maternal serum 25(OH)D levels were also
      measured. RESULTS: Median serum 25(OH)D levels for the entire sample (n = 498)
      was 27.4 ng/mL (interquartile range 20.9-32.7). Serum 25(OH)D was adequate (>= 30
      ng/mL) in only 36.1% of gravids, whereas levels were found to be insufficient (20
      29.99 ng/mL) in 41.2% and deficient (< 20 ng/mL) in 22.7%. No significant
      correlation was found between the serum 25(OH)D levels and the measured
      ultrasound parameters. CONCLUSION: First trimester 25(OH)D levels did not
      correlate to fetal ultrasound measurements.

PMID- 21877142
TI  - Tissue composition of mammographically dense and non-dense breast tissue.
AB  - Mammographic density is a strong risk factor for breast cancer but its underlying
      biology in healthy women is not well-defined. Using a novel collection of core
      biopsies from mammographically dense versus non-dense regions of the breasts of
      healthy women, we examined histologic and molecular differences between these two
      tissue types. Eligible participants were 40 + years, had a screening mammogram
      and no prior breast cancer or current endocrine therapy. Mammograms were used to
      identify dense and non-dense regions and ultrasound-guided core biopsies were
      performed to obtain tissue from these regions. Quantitative assessment of
      epithelium, stroma, and fat was performed on dense and non-dense cores. Molecular
      markers including Ki-67, estrogen receptor (ER) and progesterone receptor (PR)
      were also assessed for participants who had >0% epithelial area in both dense and
      non-dense tissue. Signed rank test was used to assess within woman differences in
      epithelium, stroma and fat between dense and non-dense tissue. Differences in
      molecular markers (Ki-67, ER, and PR) were analyzed using generalized linear
      models, adjusting for total epithelial area. Fifty-nine women, mean age 51 years
      (range: 40-82), were eligible for analyses. Dense tissue was comprised of greater
      mean areas of epithelium and stroma (1.1 and 9.2 mm(2) more, respectively) but
      less fat (6.0 mm(2) less) than non-dense tissue. There were no statistically
      significant differences in relative expression of Ki-67 (P = 0.82), ER (P =
      0.09), or PR (P = 0.96) between dense and non-dense tissue. Consistent with prior
      reports, we found that mammographically dense areas of the breast differ
      histologically from non-dense areas, reflected in greater proportions of
      epithelium and stroma and lesser proportions of fat in the dense compared to non
      dense breast tissue. Studies of both epithelial and stromal components are
      important in understanding the association between mammographic density and
      breast cancer risk.

PMID- 21877144
TI  - Hormone replacement therapy: relation to homocysteine and prooxidant-antioxidant
      status in healthy postmenopausal women.
AB  - OBJECTIVES: Studies have consistently shown a lower cardiovascular risk in women
      who received postmenopausal hormone replacement therapy (HRT). DESIGN AND
      METHODS: In this study, the effects of HRT were investigated on plasma total
      homocysteine (tHcy) and the oxidant-antioxidant status in postmenopausal women.
      35 of postmenopausal receiving (2 mg estrodiol valerate + 1 mg cyproterone
      acetate) HRT group, the remaining 25 received orally placebo (NHRT group).
      RESULTS: There was no significant change in plasma tHcy levels between HRT and
      NHRT groups. Malondialdehyde (MDA) and total thiol (t-SH) correlated
      significantly with tHcy (0.388 and 0.478, respectively) content, and there was a
      significant negative correlation between E2 level and glutathione transferase
      (GST) activity (-0.425) in HRT group. Superoxide dismutase (SOD) and HDL-C
      correlated significantly with t-SH level (0.339 and 0.336, respectively) in
      plasma after HRT. CONCLUSION: Our results show that HRT is beneficial in the
      protection against oxidative damage, and prevents atherosclerotic complications.

PMID- 21877145
TI  - The intraocular pressure response to dehydration: a pilot study.
AB  - The aim of this study was to determine the intraocular pressure response to
      differing levels of dehydration. Seven males participated in 90 min of treadmill
      walking (5 km h(-1) and 1% grade) in both temperate (22  degrees C) and hot (43 
      degrees C) conditions. At baseline and 30 min intervals intraocular pressure,
      nude body mass, body temperature and heart rate were recorded. Statistically
      significant interactions (p < 0.05) were observed for intraocular pressure (hot
      condition: baseline 17.0 +/- 2.9, 30 min 15.6 +/- 3.5, 60 min 14.5 +/- 3.7 and 90
      min 13.6 +/- 2.9 mmHg; temperate condition: baseline 16.8 +/- 2.7, 30 min 16.5 +/
      2.6, 60 min 15.8 +/- 2.5 and 90 min 15.7 +/- 1.8 mmHg) and body mass loss (hot
      condition: 30 min -1.07 +/- 0.35, 60 min -2.17 +/- 0.55 and 90 min -3.13 +/-
      0.74%; temperate condition: 30 min -0.15 +/- 0.11, 60 min -0.47 +/- 0.18 and 90
      min -0.78 +/- 0.25%). Significant linear regressions (p < 0.05) were observed for
      intraocular pressure and body mass loss (adjusted r(2) = 0.24) and intraocular
      pressure change and body mass loss (adjusted r(2) = 0.51). In conclusion,
      intraocular pressure was progressively reduced during a period of exercise
      causing dehydration, but remained relatively stable when hydration was
      maintained. The present study revealed a moderate relationship between
      dehydration (body mass loss) and intraocular pressure change.

PMID- 21877146
TI  - Muscle activity of the core during bilateral, unilateral, seated and standing
      resistance exercise.
AB  - Little is known about the effect of performing common resistance exercises
      standing compared to seated and unilaterally compared to bilaterally on muscle
      activation of the core. Thus, the purpose of this study was to compare the
      electromyographic activity (EMG) of the superficial core muscles (i.e. rectus
      abdominis, external oblique and erector spinae) between seated, standing,
      bilateral and unilateral dumbbell shoulder presses. 15 healthy males performed
      five repetitions at 80% of one-repetition maximum of the exercises in randomized
      order. Results were analyzed with a two-way analysis of variance and a Bonferroni
      post hoc test. The position * exercise interaction was significantly different
      for rectus abdominis (P = 0.016), but not for external oblique (P = 0.100) and
      erector spinae (P = 0.151). The following EMG results were observed: For rectus
      abdominis: ~49% lower in seated bilateral versus unilateral (P < 0.001), similar
      in standing bilateral versus unilateral (P = 0.408), ~81% lower in bilateral
      seated versus standing (P < 0.001), ~59% lower in unilateral seated versus
      standing (P < 0.001); For external oblique: ~81% lower in seated bilateral versus
      unilateral (P < 0.001), ~68% lower in standing bilateral than unilateral (P <
      0.001), ~58% lower in bilateral seated versus standing (P < 0.001), ~28% lower in
      unilateral seated versus standing (P = 0.002); For erector spinae: similar in
      seated bilateral versus unilateral (P = 0.737), ~18% lower in standing bilateral
      versus unilateral (P = 0.001), similar in seated versus standing bilateral (P =
      0.480) and unilateral (P = 0.690). In conclusion, to enhance neuromuscular
      activation of the superficial core muscles, standing exercises should be used
      instead of seated exercises, and unilateral exercises should be used instead of
      bilateral exercises.

PMID- 21877147
TI  - 5,6-dihydro-2H-pyranones and 5,6-dihydro-2H-pyridones and their derivatives
      modulate in vitro human T lymphocyte function.
AB  - The aim of this work was to study the in vitro effects of delta-lactone 1, delta
      lactam 3 and their enaminone derivatives 2 and 4, synthesized in our laboratory,
      on the proliferative responses of human lymphocytes, Th1 and Th2 cytokine
      secretion and intracellular redox status. Peripheral blood lymphocytes were
      isolated using differential centrifugation on a density gradient of Histopaque.
      They were cultured with mitogen concanavalin A (Con A) and with different
      concentrations of the compounds 1, 2, 3 and 4 (0.1-10 MUM). Proliferation (MTT
      assay), IL-2, INFgamma and IL-4 (Elisa kits), oxidative markers (intracellular
      glutathione, hydroperoxide and carbonyl protein contents) and cytotoxic effect
      (micronucleus test) were determined. The compounds 1 and 2 are immunosuppressive
      and decrease IL-2, INFgamma and IL-4 secretion with a shift away from Th2
      response to Th1 phenotype. The compounds 3 and 4 were immunostimulant and
      increased cytokine secretion with a shift away from Th1 response to Th2. The
      introduction of an enamine group to 1 and 3 to provide 2 and 4 seemed to
      attenuate their immunological properties. These immunomodulatory properties were,
      however, accompanied by an increase in lymphocyte intracellular oxidative stress,
      especially with 1 and 2 at high concentrations. In conclusion, the compounds 1,
      2, 3 and 4 could be used to provide cell-mediated immune responses for novel
      therapies in T-cell mediated immune disorders.

PMID- 21877148
TI  - Effect of sydnone SYD-1 on certain functions of LPS-stimulated macrophages.
AB  - In an earlier article, we demonstrated that sydnone SYD-1 (3-[4-chloro-3
      nitrophenyl]-1,2,3-oxadiazolium-5-olate) inhibits electron transport in the
      respiratory chain and uncouples oxidative phosphorylation, and postulated that
      these effects are probably involved in its antitumor activity. We now report the
      effect of SYD-1 on certain macrophage functions, considering the important role
      of these cells in inflammatory response and also the relevant anti-inflammatory
      activity reported for some sydnones. Incubation of macrophages with SYD-1 (5-100
      MUM) for 48 h did not affect the cell viability up to a concentration of 50 MUM.
      However, at the highest concentration (100 MUM), the compound decreased
      macrophage viability by ~20%. In assays involving 2 h and 24 h of incubation, SYD
      1 (5-100 MUM) did not affect the cell viability. The incubation of macrophages
      with the compound for 2 h promoted a dose-dependent reduction of phagocytic
      activity of up to ~65% (100 MUM). SYD-1 (100 MUM) was also able to increase the
      production of superoxide anion (~50%). In the absence of LPS, SYD-1 decreased NO
      production dose-dependently by up to ~80% (100 MUM). When SYD-1 and LPS were
      incubated concomitantly, the decrease of NO promoted by SYD was the most
      pronounced, reaching up to ~98% at the same concentration (50 MUM). SYD-1 dose
      dependently suppressed IL-6 secretion by LPS-stimulated macrophages, reaching up
      to ~90% of inhibition at the highest concentration (100 MUM). These results
      indicate that SYD-1 promotes effects similar to those described for anti
      inflammatory and immunosuppressive drugs, thus motivating further studies to
      clarify the mechanisms involved in this activity.

PMID- 21877149
TI  - [76-year old patient with suspected but not confirmed "idiopathic
      myelofibrosis"].
AB  - A 76-year old patient was referred to our Oncology Unit due to
      hepatosplenomegaly, anemia, thrombocytopenia, eosinophilia, elevation of lactat
      dehydrogenase and leucocytosis with occurrence of myeloid and erythroid
      precursors in the peripheral blood. Histopathological examination of the bone
      marrow and molecular genetics showing a c-kit-D816V-mutation confirmed the
      diagnosis of systemic mastocytosis without evidence of idiopathic myelofibrosis.
      After starting of prednisone treatment anemia, thromocytopenia and the patient's
      performance status rapidly improved.

PMID- 21877150
TI  - Mapping of the S. demissum late blight resistance gene R8 to a new locus on
      chromosome IX.
AB  - The use of resistant varieties is an important tool in the management of late
      blight, which threatens potato production worldwide. Clone MaR8 from the
      Mastenbroek differential set has strong resistance to Phytophthora infestans, the
      causal agent of late blight. The F1 progeny of a cross between the susceptible
      cultivar Concurrent and MaR8 were assessed for late blight resistance in field
      trials inoculated with an incompatible P. infestans isolate. A 1:1 segregation of
      resistance and susceptibility was observed, indicating that the resistance gene
      referred to as R8, is present in simplex in the tetraploid MaR8 clone. NBS
      profiling and successive marker sequence comparison to the potato and tomato
      genome draft sequences, suggested that the R8 gene is located on the long arm of
      chromosome IX and not on the short arm of chromosome XI as was suggested
      previously. Analysis of SSR, CAPS and SCAR markers confirmed that R8 was on the
      distal end of the long arm of chromosome IX. R gene cluster directed profiling
      markers CDP(Sw5)4 and CDP(Sw5)5 flanked the R8 gene at the distal end (1 cM).
      CDP(Tm2)1-1, CDP(Tm2)1-2 and CDP(Tm2)2 flanked the R8 gene on the proximal side
      (2 cM). An additional co-segregating marker (CDP(Hero)3) was found, which will be
      useful for marker assisted breeding and map based cloning of R8.

PMID- 21877151
TI  - Characteristics and nature of the intermolecular interactions in boron-bonded
      complexes with carbene as electron donor: an ab initio, SAPT and QTAIM study.
AB  - We report geometries, stabilization energies, symmetry adapted perturbation
      theory (SAPT) and quantum theory of atoms in molecules (QTAIM) analyses of a
      series of carbene-BX(3) complexes, where X = H, OH, NH(2), CH(3), CN, NC, F, Cl,
      and Br. The stabilization energies were calculated at HF, B3LYP, MP2, MP4 and
      CCSD(T)/aug-cc-pVDZ levels of theory using optimized geometries of all the
      complexes obtained from B3LYP/aug-cc-pVTZ. Quantitatively, all the complexes
      indicate the presence of B-C(carbene) interaction due to the short B-C(carbene)
      distances. Inspection of stabilization energies reveals that the interaction
      energies increase in the order NH(2) > OH > CH(3) > F > H > Cl > Br > NC > CN,
      which is the opposite trend shown in the binding distances. Considering the SAPT
      results, it is found that electrostatic effects account for about 50% of the
      overall attraction of the studied complexes. By comparison, the induction
      components of these interactions represent about 40% of the total attractive
      forces. Despite falling in a region of charge depletion with nabla(2)rho(BCP) >0,
      the B-C(carbene) bond critical points (BCPs) are characterized by a reasonably
      large value of the electron density (rho(BCP)) and H(BCP) <0, indicating that the
      potential energy overcomes the kinetic energy density at BCP and the B-C(carbene)
      bond is a polar covalent bond.

PMID- 21877152
TI  - Combinatorial screening of polymer precursors for preparation of benzo[alpha]
      pyrene imprinted polymer: an ab initio computational approach.
AB  - A combinatorial screening procedure was used for the selection of polymer
      precursors in the preparation of molecularly imprinted polymer (MIP), which is
      useful in the detection of the air pollution marker molecule benzo[a]pyrene
      (BAP). Molecular imprinting is a technique for the preparation of polymer
      materials with specific molecular recognition receptors. The preparation of
      imprinted polymers requires polymer precursors such as functional monomer, cross
      linking monomer, solvent, an initiator of polymerization and thermal or UV
      radiation. A virtual library of functional monomers was prepared based on
      interaction binding scores computed using HyperChem Release 8.0 software.
      Initially, the possible minimum energy conformation of the monomers and BAP were
      optimized using the semi-empirical (PM3) quantum method. The binding energy
      between the functional monomer and the template (BAP) was computed using the
      Hartree-Fock (HF) method with 6-31 G basis set, which is an ab initio approach
      based on Moller-Plesset second order perturbation theory (MP2). From the
      computations, methacrylic acid (MAA) and ethylene glycol dimethacrylate (EGDMA)
      were selected for preparation of BAP imprinted polymer. The larger interaction
      energy (DeltaE) represents possibility of more affinity binding sites formation
      in the polymer, which provides high binding capacity. The theoretical predictions
      were complimented through adsorption experiments. There is a good agreement
      between experimental binding results and theoretical computations, which provides
      further evidence of the validity of the usefulness of computational screening
      procedures in the selection of appropriate MIP precursors in an experiment-free
      way.

PMID- 21877153
TI  - Transient pockets on XIAP-BIR2: toward the characterization of putative binding
      sites of small-molecule XIAP inhibitors.
AB  - Protein-protein interactions are abundant in signal transduction pathways and
      thus of crucial importance in the regulation of apoptosis. However, designing
      small-molecule inhibitors for these potential drug targets is very challenging as
      such proteins often lack well-defined binding pockets. An example for such an
      interaction is the binding of the anti-apoptotic BIR2 domain of XIAP to the pro
      apoptotic caspase-3 that results in the survival of damaged cells. Although small
      molecule inhibitors of this interaction have been identified, their exact binding
      sites on XIAP are not known as its crystal structures reveal no suitable pockets.
      Here, we apply our previously developed protocol for identifying transient
      binding pockets to XIAP-BIR2. Transient pockets were identified in snapshots
      taken during four different molecular dynamics simulations that started from the
      caspase-3:BIR2 complex or from the unbound BIR2 structure and used water or
      methanol as solvent. Clustering of these pockets revealed that surprisingly many
      pockets opened in the flexible linker region that is involved in caspase-3
      binding. We docked three known inhibitors into these transient pockets and so
      determined five putative binding sites. In addition, by docking two inactive
      compounds of the same series, we show that this protocol is also able to
      distinguish between binders and nonbinders which was not possible when docking to
      the crystal structures. These findings represent a first step toward the
      understanding of the binding of small-molecule XIAP-BIR2 inhibitors on a
      molecular level and further highlight the importance of considering protein
      flexibility when designing small-molecule protein-protein interaction inhibitors.

PMID- 21877155
TI  - Studies on molecular structure and tautomerism of a vitamin B6 analog with
      density functional theory.
AB  - This work presents a computational study on the molecular structure and
      tautomeric equilibria of a novel Schiff base L derived from pyridoxal (PL) and o
      phenylenediamine by using the density functional method B3LYP with basis sets 6
      31 G(d,p), 6-31++G(d,p), 6-311 G(d,p) and 6-311++G(d,p). The optimized
      geometrical parameters obtained by B3LYP/6-31 G(d,p) method showed the best
      agreement with the experimental values. Tautomeric stability study of L inferred
      that the enolimine form is more stable than its ketoenamine form in both gas
      phase and solution. However, protonation of the pyridoxal nitrogen atom (LH) have
      accelerated the formation of ketoenamine form, and therefore, both ketoenamine
      and enolimine forms could be present in acidic media.

PMID- 21877154
TI  - In silico analysis of Pycnoporus cinnabarinus laccase active site with toxic
      industrial dyes.
AB  - Laccases belong to multicopper oxidases, a widespread class of enzymes implicated
      in many oxidative functions in various industrial oxidative processes like
      production of fine chemicals to bioremediation of contaminated soil and water. In
      order to understand the mechanisms of substrate binding and interaction between
      substrates and Pycnoporus cinnabarinus laccase, a homology model was generated.
      The resulted model was further validated and used for docking studies with toxic
      industrial dyes- acid blue 74, reactive black 5 and reactive blue 19.
      Interactions of chemical mediators with the laccase was also examined. The
      docking analysis showed that the active site always cannot accommodate the dye
      molecules, due to constricted nature of the active site pocket and steric
      hindrance of the residues whereas mediators are relatively small and can easily
      be accommodated into the active site pocket, which, thereafter leads to the
      productive binding. The binding properties of these compounds along with
      identification of critical active site residues can be used for further site
      directed mutagenesis experiments in order to identify their role in activity and
      substrate specificity, ultimately leading to improved mutants for degradation of
      these toxic compounds.

PMID- 21877156
TI  - Theoretical study of the local reactivity of electrophiles of the type MPR3(+) (M
      = Cu, Ag, Au; R = -H, -Me, -Ph).
AB  - Reactivity prediction in the series of MPR(3)(+) fragments ( M = Au, Ag, Cu; R = 
      H, -Me, -Ph) has been achieved at the ab initio (HF and MP2) and density
      functional theory (B3LYP and PBE) levels. We have used global and local
      descriptors based on conceptual DFT such as hardness, Fukui function and
      electrophilicity index. For all methods and fragments, we have found an equal
      trend in reactivity using both the global and local electrophilicity index: QR
      AuPR(3)(+) > CuPR(3)(+) ~ AgPR(3)(+) > NR-AuPR(3)(+). It is also found that the
      electrophilicity power decreases as the volume of R increases.

PMID- 21877157
TI  - Density functional theory study on the interaction between keto-9H guanine and
      aspartic acid.
AB  - A theoretical study was performed using density functional theory (DFT) to
      investigate hydrogen bonding interactions in signature complexes formed between
      keto-9H guanine (Gua) and aspartic acid (Asp) at neutral pH. Optimized
      geometries, binding energies and the theoretical IR spectra of guanine, aspartic
      acid and their corresponding complexes (Gua-Asp) were calculated using the B3LYP
      method and the 6-31+G(d) basis set. Stationary points found to be at local minima
      on the potential energy surface were verified by second derivative harmonic
      vibrational frequency calculations at the same level of theory. AIM theory was
      used to analyze the hydrogen bonding characteristics of these DNA base complex
      systems. Our results show that the binding motif for the most stable complex is
      strikingly similar to a Watson-Crick motif observed in the guanine-cytosine base
      pair. We have found a range of hydrogen bonding interactions between guanine and
      aspartic acid in the six complexes. This was further verified by theoretical IR
      spectra of omega(C-H--O-H) cm(-1) stretches for the Gua-Asp complexes. The
      electron density plot indicates strong hydrogen bonding as shown by the 2p(z)
      dominant HOMO orbital character.

PMID- 21877158
TI  - Human type 2 17beta-hydroxysteroid dehydrogenase in umbilical vein and artery
      endothelial cells: differential inactivation of sex steroids according to the
      vessel type.
AB  - The human placenta produces high amounts of estradiol. 17beta-hydroxysteroid
      dehydrogenase type 2 (17betaHSD2) is expressed by placental endothelial cells and
      was proposed to regulate sex hormone levels. Previous results obtained in term
      placenta suggested that 17betaHSD2 expression and activity differ among umbilical
      cord vessels. In this study, 17betaHSD2 expression level and enzymatic activity,
      and estrogen receptor alpha and beta expression levels, were measured in
      endothelial cell cultures from umbilical arteries (HUAEC) and vein (HUVEC) using
      real-time quantitative PCR, western blot, and radiolabeled steroids. 17betaHSD2
      specific activities were also measured in proximal and distal segments of freshly
      isolated umbilical cord arteries and vein. 17betaHSD2 mRNA level and activity
      were higher in HUAEC than in HUVEC. Activity was higher in umbilical arteries
      than in the umbilical vein. In arteries, enzymatic activity was higher near the
      placenta, suggesting a gradient of expression. No difference was found in ERalpha
      expression, whereas ERbeta was expressed at a higher level in HUAEC than in
      HUVEC. Expression profiles of estrogen receptors and 17betaHSD2 suggest a vessel
      type-specific response to estrogens. Our data support a differential modulation
      of biologically active sex steroid levels according to the vessel type in the
      foeto-placental unit, with apparent higher inactivation in the arterial system.

PMID- 21877159
TI  - Gastric emptying after sleeve gastrectomy.

PMID- 21877160
TI  - New drugs for bipolar disorder.
AB  - Bipolar disorder (BD) is one of the most potentially severe mental disorders.
      Literature data indicate that despite the current available treatments, a large
      proportion of patients do not achieve complete remission, with consequent
      residual symptoms and chronic impairment. We carried out a comprehensive review
      of new pharmacologic treatments for BD. Even though the core treatment of BD
      likely will not likely undergo substantial changes over the next few years, many
      promising results with respect to new augmentation strategies were identified.
      New treatments for bipolar depression and for BD-related cognitive impairment
      seem to represent particularly fertile areas of research.

PMID- 21877161
TI  - When she says "no" to medication: psychotherapy for antepartum depression.
AB  - Many women suffering from major depressive disorder during pregnancy are hesitant
      to initiate or continue antidepressant treatment during preconception planning,
      conception, pregnancy, and lactation (perinatal period). Over the past few
      decades, various psychotherapeutic approaches have been found to be efficacious
      for depression in general population research. Several observational and quasi
      experimental studies also suggest that psychotherapy can be a safe first-line
      treatment for perinatal women with mild to moderate depression. This article
      summarizes findings to date regarding the use of psychotherapy for depression
      occurring during pregnancy and describes the adaptations made to tailor the
      treatment to the unique needs of women in the perinatal period.

PMID- 21877162
TI  - Freiburg neuropathology case conference: a mass lesion of the mesial temporal
      lobe in a child.

PMID- 21877164
TI  - Natural history of Camponotus ant-fishing by the M group chimpanzees at the
      Mahale Mountains National Park, Tanzania.
AB  - The aim of this study was to provide basic data on ant-fishing behavior among the
      M group chimpanzees at the Mahale Mountains National Park, Tanzania. Ant-fishing
      is a type of tool-using behavior that has been exhibited by Mahale chimpanzees
      when feeding upon arboreal carpenter ants (Camponotus spp.) since the 1970s, and
      is now regarded as a candidate of wild chimpanzee culture. Herein, I describe in
      detail the features of ant-fishing shown by the Mahale M group chimpanzees: (1) 2
      species of Camponotus ants (Camponotus sp. (chrysurus-complex) [C. sp.1] and C.
      brutus) were identified as the target species of ant-fishing, and C. sp.1 was
      selected intensively as the main target; (2) 24 species (92 individuals) of trees
      were identified as ant-fishing sites-these were widely distributed throughout the
      western/lowland region of the M group's home range, and the top 5 species were
      used more frequently; (3) the efficiency of ant-fishing was influenced not only
      by the site choice or the skillfulness of the chimpanzees, but inevitably by the
      condition of the ants; (4) the estimated nutritional intake from ant-fishing was
      apparently negligible; (5) most of the M group members (50/60 individuals) older
      than 3 years of age successfully used tools to fish for ants; and (6) female
      chimpanzees engaged in ant-fishing more frequently and for longer periods than
      males did. Further, I compared the features of ant-fishing exhibited by the
      Mahale M group chimpanzees with those exhibited by the former K group at Mahale
      and by other populations of wild chimpanzees.

PMID- 21877169
TI  - Eculizumab in atypical hemolytic uremic syndrome: long-term clinical course and
      histological findings.
AB  - Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy
      associated with defective regulation of the alternative complement pathway. The
      prognosis for patients with aHUS is poor, and plasma exchange represents the
      first-line therapy. Eculizumab is a humanized monoclonal anti-C5 antibody that
      prevents the activation of the terminal complement pathway. Here, we report the
      case of a 9-year-old girl with frequent relapsing aHUS due to heterozygous factor
      H mutation who was initially treated with plasma exchange three times per week
      with 150% plasma exchange volume. This treatment frequently caused allergic
      reactions and school absences. Because any reduction in the frequency of plasma
      exchange immediately induced relapses of the aHUS, treatment with eculizumab, 600
      mg every 2 weeks, was started and plasma exchange completely stopped. On this
      drug regimen the patient showed no evidence of disease activity during a period
      of more than 24 months. Renal function improved, proteinuria disappeared, the
      number of antihypertensive medications could be decreased, and the quality of
      life increased substantially. The inhibition of the terminal complement pathway
      by eculizumab was also confirmed by renal biopsy, which showed the absence of
      thrombotic microangiopathy 2 months after the initiation of eculizumab therapy.
      This case illustrates the long-term favorable outcome of aHUS with eculizumab
      treatment.

PMID- 21877166
TI  - Biokinetics and dosimetry of commonly used radiopharmaceuticals in diagnostic
      nuclear medicine - a review.
AB  - PURPOSE: The impact on patients' health of radiopharmaceuticals in nuclear
      medicine diagnostics has not until now been evaluated systematically in a
      European context. Therefore, as part of the EU-funded Project PEDDOSE.NET (
      www.peddose.net ), we review and summarize the current knowledge on biokinetics
      and dosimetry of commonly used diagnostic radiopharmaceuticals. METHODS: A
      detailed literature search on published biokinetic and dosimetric data was
      performed mostly via PubMed ( www.ncbi.nlm.nih.gov/pubmed ). In principle the
      criteria for inclusion of data followed the EANM Dosimetry Committee guidance
      document on good clinical reporting. RESULTS: Data on dosimetry and biokinetics
      can be difficult to find, are scattered in various journals and, especially in
      paediatric nuclear medicine, are very scarce. The data collection and calculation
      methods vary with respect to the time-points, bladder voiding, dose assessment
      after the last data point and the way the effective dose was calculated. In many
      studies the number of subjects included for obtaining biokinetic and dosimetry
      data was fewer than ten, and some of the biokinetic data were acquired more than
      20 years ago. CONCLUSION: It would be of interest to generate new data on
      biokinetics and dosimetry in diagnostic nuclear medicine using state-of-the-art
      equipment and more uniform dosimetry protocols. For easier public access to
      dosimetry data for diagnostic radiopharmaceuticals, a database containing these
      data should be created and maintained.

PMID- 21877168
TI  - When and how to start prevention of atherosclerosis? Lessons from the
      Cardiovascular Risk in the Young Finns Study and the Special Turku Coronary Risk
      Factor Intervention Project.
AB  - This review provides an up-to-date summary of findings from two ongoing
      population-based, prospective studies conducted in Finland: The Cardiovascular
      Risk in Young Finns Study, and the Special Turku Coronary Risk Factor
      Intervention Project (STRIP), which have contributed significantly to the
      scientific literature concerning the childhood origin of cardiovascular disease,
      and whether prevention efforts in adults can be expanded to young people. From
      the Young Finns Study, we summarize evidence demonstrating childhood risk factors
      to be associated with both risk factors and preclinical markers of
      atherosclerosis in adulthood, and from STRIP, we summarize evidence showing that
      supervised dietary counseling of a low saturated fat diet effectively decreases
      exposure to cardiovascular risk factors without affecting growth and development
      of healthy children and adolescents. The evidence available from these studies
      supports that the ability to prevent or delay the risk of premature
      atherosclerosis and its clinical sequelae later in life lies in maintaining a low
      lifetime risk by preventing the development of risk factors in early life.

PMID- 21877170
TI  - Using new media to reach Hispanic/Latino cancer survivors.
AB  - In the USA, cancer is a leading cause of morbidity and premature death among the
      Hispanic/Latino population. It is estimated that one in two Hispanic men and one
      in three Hispanic women will be diagnosed with cancer during their lifetime
      (American Cancer Society 2010). Despite this significant cancer burden, few
      innovative strategies for communication and outreach to this population currently
      exist. In 2009, LIVESTRONG launched a national outreach campaign, which utilized
      social marketing, specifically targeting Hispanics with the goal of increasing
      awareness and usage of LIVESTRONG's Spanish-language cancer navigation resources.
      This campaign, one of the first undertaken by a national cancer-related
      organization, led to increased awareness and utilization of resources, including
      a 238% increase in traffic over traditional marketing campaigns which focused on
      radio alone. The success of this campaign highlights the use of social media as a
      cost-effective method to raise awareness of cancer resources among Hispanics.

PMID- 21877163
TI  - The Rotterdam Study: 2012 objectives and design update.
AB  - The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city
      of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine,
      hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and
      respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise
      the Rotterdam Study cohort. The findings of the Rotterdam Study have been
      presented in over a 1,000 research articles and reports (see www.erasmus
      epidemiology.nl/rotterdamstudy ). This article gives the rationale of the study
      and its design. It also presents a summary of the major findings and an update of
      the objectives and methods.

PMID- 21877171
TI  - Enhanced urothelial expression of human chorionic gonadotropin beta (hCGbeta) in
      bladder pain syndrome/interstitial cystitis (BPS/IC).
AB  - PURPOSE: Bladder pain syndrome/interstitial cystitis (BPS/IC) is associated with
      urothelial lesions. Pathomechanisms of urothelial damage and factors for
      urothelial restoration are unknown. hCG is a factor for cellular differentiation,
      angiogenesis and immune competence of the endometrium during pregnancy. Clinical
      observations demonstrate improvement of BPS/IC symptoms during pregnancy or
      during infertility treatment with hCG. Our research aims were to examine the
      expression of hCG and luteinizing hormone receptor (LHR) in the urothelium of
      BPS/IC patients and compare the levels of hCGbeta with healthy controls. METHODS:
      Bladder biopsies of BPS/IC (CLSM: n = 10; qPCR: n = 15); Tumour-free control
      tissue from cystectomies (n = 12). hCGalpha, hCGbeta and LHR expression were
      examined by confocal laser scanning microscopy (CLSM), and hCGbeta expression was
      quantified. hCGbeta5 and hCGbeta7 mRNA splice variants were quantified in real
      time polymerase chain reaction. RESULTS: We found constitutive expression of
      hCGalpha, hCGbeta and LHR in healthy controls. HCGbeta was significantly
      upregulated in BPS/IC patients in CLSM. PCR analysis revealed higher levels of
      hCGbeta7 than hCGbeta5 in controls and BPS/IC patients. CONCLUSIONS: The
      constitutive expression of hCG and LHR speaks in favour for a functional
      signalling in urothelial cells without any association with either pregnancy or
      tumour. We show for the first time that hCGbeta is upregulated in BPS/IC
      urothelium and that hCGbeta7 is the dominant splice variant in those cells. Our
      findings imply a major role of hCG for urothelial integrity and a disturbance of
      hCG signalling in case of BPS/IC. We conclude that hCG could gain therapeutical
      relevance in the future.

PMID- 21877172
TI  - Age-specific PCA3 score reference values for diagnosis of prostate cancer.
AB  - PURPOSE: We evaluated the impact of age on PCA3 score and the utility of age
      specific reference values in predicting initial prostate biopsy (pBx) outcomes.
      PATIENTS AND METHODS: This single-center, retrospective study included 205 men
      who underwent an initial 14-core TRUS-guided pBx due to PSA > 3.0 ng/ml or
      suspicious digital-rectal examination (DRE). PCA3 scores were measured with the
      Progensa assay. Linear regression models were fit to identify factors that impact
      PCA3 score and to determine age-specific reference values. Predictive accuracies
      of logistic regression models predicting presence of prostate cancer (PCa) were
      analyzed. RESULTS: The positive biopsy rate was 37%. In multivariable linear
      regression, age (P < 0.001), presence of PCa (P < 0.001), and multifocal HG-PIN
      (P = 0.012) were independent predictors of PCA3 score. Age showed the strongest
      impact on PCA3 score (T = 4.77). The upper 95% confidence interval of PCA3 score
      in each age category was defined as the age-specific limit. A PCA3-score over the
      age-specific limit (PCA3-age) was associated with an 4.17-fold increased odds of
      being diagnosed with PCa (P < 0.001). In multivariable logistic regression models
      predicting the presence of PCa, predictive accuracy of a base model (age, DRE,
      PSA, volume) increased from 69.6 to 75.4% (P = 0.037) by adding the continuous
      PCA3 score, to 73.9% (P = 0.098) with the 35 cutoff (PCA3-35) and to 77.1% (P =
      0.008) with PCA3-age. CONCLUSIONS: PCA3 score increases with age, independent of
      PCa presence. Age-specific PCA3 score reference values are superior to PSA,
      continuous PCA3 score, and PCA3-35 in predicting initial pBx outcome. Therefore,
      an age-adjusted PCA3 score should be used for interpretation of the results.

PMID- 21877173
TI  - Arterial spin labeling MR imaging for characterisation of renal masses in
      patients with impaired renal function: initial experience.
AB  - OBJECTIVES: To retrospectively evaluate the feasibility of arterial spin labeling
      (ASL) magnetic resonance imaging (MRI) for the assessment of vascularity of renal
      masses in patients with impaired renal function. METHODS: Between May 2007 and
      November 2008, 11/67 consecutive patients referred for MRI evaluation of a renal
      mass underwent unenhanced ASL-MRI due to moderate-to-severe chronic or acute
      renal failure. Mean blood flow in vascularised and non-vascularised lesions and
      the relation between blood flow and final diagnosis of malignancy were correlated
      with a 2-sided homogeneous variance t-test and the Fisher Exact Test,
      respectively. A p value <0.05 was considered statistically significant. RESULTS:
      Seventeen renal lesions were evaluated in 11 patients (8 male; mean age = 70
      years) (range 57-86). The median eGFR was 24 mL/min/1.73 m(2) (range 7-39). The
      average blood flow of 11 renal masses interpreted as ASL-positive (134 +/- 85.7
      mL/100 g/min) was higher than that of 6 renal masses interpreted as ASL-negative
      (20.5 +/- 8.1 mL/100 g/min)(p = 0.015). ASL-positivity correlated with malignancy
      (n = 3) or epithelial atypia (n = 1) at histopathology or progression at follow
      up (n = 7). CONCLUSIONS: ASL detection of vascularity in renal masses in patients
      with impaired renal function is feasible and seems to indicate neoplasia although
      the technique requires further evaluation. KEY POINTS: Arterial spin labeling may
      help to characterise renal masses in patients with renal failure Detection of
      blood flow on ASL in a renal mass supports the presence of a neoplasm Renal
      masses with high blood-flow levels on ASL seem to progress rapidly.

PMID- 21877174
TI  - Directive support, nondirective support, and health behaviors in a community
      sample.
AB  - Social support is associated with improved psychological functioning, physical
      health, and health-promoting behaviors. However, research suggests that health
      outcomes might depend upon the type rather than the amount of support provided to
      recipients. This study assessed the relationship among nondirective and directive
      support, and health behaviors (i.e., physical activity, fruit and vegetable
      intake, alcohol use) in a community sample of 304 adults. Results revealed that
      nondirective support was related to greater fruit and vegetable intake and lower
      alcohol use; directive support was not associated with these behaviors. For
      physical activity, a similar trend emerged, but support variables did not explain
      any variance above that explained by demographic variables. These findings offer
      a unique contribution to the literature, as they suggest that certain types of
      supportive behaviors are important in encouraging positive health behaviors.

PMID- 21877175
TI  - Streptococcus pyogenes bacteraemia, emm types and superantigen profiles.
AB  - The aim of this study was to investigate the emm types and superantigen profiles
      of bacteraemic group A streptococcal (GAS; Streptococcus pyogenes) isolates and
      to detect possible associations between the molecular characteristics of isolates
      and the clinical presentations of disease. In this population-based study, 87
      bacteraemic GAS isolates from adult patients in Pirkanmaa Health District (HD),
      Finland, during the period 1995-2004 were emm typed and genotyped for
      superantigen (SAg) profiles. The epidemiological and clinical data of the
      patients were analysed with the microbiological characterisation data. Among the
      87 isolates, 18 different emm types were found. emm1, emm28 and emm81 were the
      three most common types, covering 52% of isolates. The prevalence of specific emm
      types showed high variability during the 10-year study period. We could not find
      any association between the emm type and clinical features of bacteraemic
      infection, such as underlying diseases, disease manifestations or case fatality.
      Of nine superantigen genes examined, speA and speC were identified in 20 and 30%
      of the strains, respectively. No association was found between disease
      manifestation and the presence of single superantigen genes. The 26-valent GAS
      vaccine would have covered only 62% of isolates causing invasive disease in
      Pirkanmaa HD during the study period.

PMID- 21877176
TI  - Associative learning phenomena in the snail (Helix aspersa): conditioned
      inhibition.
AB  - Two experiments using garden snails (Helix aspersa) showed conditioned inhibition
      using both retardation and summation tests. Conditioned inhibition is a procedure
      by which a stimulus becomes a predictor of the absence of a relevant event--the
      unconditioned stimulus (US). Typically, conditioned inhibition consists of
      pairings between an initially neutral conditioned stimulus, CS(2), and an
      effective excitatory conditioned stimulus, CS(1), in the absence of the US.
      Retardation and summation tests are required in order to confirm that CS(2) has
      acquired inhibitory properties. Conditioned inhibition has previously been found
      in invertebrates; however, these demonstrations did not use the retardation and
      summation tests required for an unambiguous demonstration of inhibition, allowing
      for alternative explanations. The implications of our results for the fields of
      comparative cognition and invertebrate physiological models of learning are
      discussed.

PMID- 21877177
TI  - Effects of oligomycin on transient currents carried by Na+ translocation of Bufo
      Na+/K(+)-ATPase expressed in Xenopus oocytes.
AB  - Na(+)/K(+)-ATPase (NKA) exports 3Na(+) and imports 2K(+) at the expense of the
      hydrolysis of 1ATP under physiological conditions. In the absence of K(+), it can
      mediate electroneutral Na(+)/Na(+) exchange. In the electroneutral Na(+)/Na(+)
      exchange mode, NKA produces a transient current containing fast, medium and slow
      components in response to a sudden voltage step. These three components of the
      transient current demonstrate the sequential release of Na(+) ions from three
      binding sites. Our data from oocytes provide further experimental support for the
      existence of these components. Oligomycin is an NKA inhibitor that favors the
      2Na(+)-occluded state without affecting the conformational state of the NKA. We
      studied the effects of oligomycin on both K(+)-activated currents and transient
      currents in wild-type Bufo NKA and a mutant form of Bufo NKA, NKA: G813A.
      Oligomycin blocked almost all of the K(+)-activated current, although the three
      components of the transient current showed different sensitivities to oligomycin.
      The oligomycin-inhibited charge movement measured using a P/4 protocol had a rate
      coefficient similar to the medium transient component. The fast component of the
      transient current elicited by a short voltage step also showed sensitivity to
      oligomycin. However, the slow component was not totally inhibited by oligomycin.
      Our results indicate that the second and third sodium ions might be released to
      the extracellular medium by a mechanism that is not shared by the first sodium
      ion.

PMID- 21877178
TI  - Implementing strategic bundles for infection prevention and management.
AB  - Healthcare-associated infections (HAI) are considered to be the most frequent
      adverse event in healthcare delivery. Active efforts to curb HAI have increased
      across Europe thanks to the growing emphasis on patient safety and quality of
      care. Recently, there has been dramatic success in improving the quality of
      patient care by focusing on the implementation of a group or "bundle" of
      evidenced-based preventive practices to achieve a better outcome than when
      implemented individually. The project entitled IMPLEMENT is designed to spread
      and test knowledge on how to implement strategic bundles for infection prevention
      and management in a diverse sample of European hospitals. The general goal of
      this project is to provide evidence on how to decrease the incidence of HAI and
      to improve antibiotic use under routine conditions.

PMID- 21877179
TI  - First case of anti-ganglioside GM1-positive Guillain-Barre syndrome due to
      hepatitis E virus infection.
AB  - A 51-year-old previously healthy woman presented with Guillain-Barre syndrome
      (GBS) and elevated liver enzymes. Further diagnostic investigations showed the
      presence of an acute hepatitis E infection associated with anti-ganglioside GM1
      antibodies. After treatment with intravenous immunoglobulins, the patient made a
      rapid recovery. Here, we report the first case of GBS due to acute hepatitis E
      virus (HEV) infection associated with the presence of anti-ganglioside GM1
      antibodies. We also review available literature on the association between acute
      HEV infection and GBS.

PMID- 21877180
TI  - Miller-Fisher syndrome following vaccination against influenza virus A/H1N1 in an
      AIDS patient.

PMID- 21877181
TI  - Rat bite fever as a presenting illness in a patient with AIDS.
AB  - The etiology of culture-negative septic arthritis is poorly characterised in
      persons infected with human immunodeficiency virus (HIV). New molecular methods
      may assist in the investigation of culture-negative infections of sterile sites,
      including septic arthritis. We describe the first case of septic arthritis due to
      the cause of rat bite fever (RBF), Streptobacillus moniliformis, confirmed by 16S
      rRNA sequence analysis, in a patient with newly diagnosed HIV infection.

PMID- 21877182
TI  - Listeria meningitis and ventriculitis in an immunocompetent child: case report
      and literature review.
AB  - Listeria monocytogenes meningitis is very rare in immunocompetent children. We
      present a case of a previously healthy 6-year-old girl who developed L.
      monocytogenes meningitis and ventriculitis. We also review the medical literature
      on non-neonatal L. monocytogenes meningitis in immunocompetent children.

PMID- 21877183
TI  - Recent advances in the understanding of genetic susceptibility to chronic pain
      and somatic symptoms.
AB  - Regional (e.g., low back) and widespread chronic pain disorders are common in the
      general population and are known to be heritable. Recent research suggests that
      genetic factors increase the risk of developing chronic pain independent of the
      site of pain. Candidate gene studies have been conducted on key pathways to
      elucidate susceptibility genes that are likely to be involved in both the sensory
      and affective components of pain. Findings have been largely equivocal,
      predominantly due to small sample size, but larger studies of pain in general
      population samples are being conducted. Interesting candidate genes from animal
      models and monogenic pain disorders are beginning to emerge. Recent advances in
      genetics research have yet to make an impact in the pain field but provide
      considerable scope for future research efforts.

PMID- 21877184
TI  - Analysis of mono-phosphate nucleotides as a potential method for quantification
      of DNA using high performance liquid chromatography-inductively coupled plasma
      mass spectrometry.
AB  - The determination of total deoxyribonucleic acid (DNA) concentration is of great
      importance in many biological and bio-medical analyses. The quantification of DNA
      is traditionally performed by UV spectroscopy; however the results can be
      affected greatly by the sample matrix. The proposed method quantifies phosphorus
      in digested calf thymus DNA and human DNA by high performance liquid
      chromatography (HPLC) combined with inductively coupled plasma mass spectrometry
      (ICP-MS). The method presented showed excellent baseline separation between all
      four DNA mono-nucleotides and 5'UMP. The ability of LC-ICP-MS to provide an
      internal check that only DNA derived phosphorus was counted in the assay was
      demonstrated by establishing a mass balance between the total phosphorous signal
      from undigested DNA and that from the speciated DNA. Column recoveries ranging
      from 95% to 99% for phosphorus resulted in a mass balance of 95% +/- 0.5% for
      standard nucleotides, determined by LC-ICP-MS, compared to total DNA determined
      by flow injection coupled to ICP-MS (FI-ICP-MS). The method for quantification
      was validated by analysis of NIST SRM 2,372; a total speciated DNA recovery of
      52.1 ng/MUL, compared with an expected value of 53.6 ng/MUL, was determined by
      external calibration. From repeat measurements, a mass balance of 97% +/- 0.5%
      for NIST DNA was achieved. The method limits of detection for individual
      nucleotides were determined between 0.8 and 1.7 MUg L(-1) ((31)P) for individual
      nucleotides by LC-ICP-MS, and 360 ng L(-1) for 5'AMP by direct nebulisation.

PMID- 21877185
TI  - Speciation analysis of bromine-containing drug metabolites in feces samples from
      a human in vivo study by means of HPLC/ICP-MS combined with on-line isotope
      dilution.
AB  - The aim of this work was speciation analysis of metabolites in feces samples
      collected within a clinical study during which a bromine-containing anti
      tuberculosis drug (TMC207) was administered to patients with multi-drug resistant
      tuberculosis infection. Owing to slow elimination of the drug, no (14)C label was
      used within this study. Quantification of the bromine species was accomplished
      using high performance liquid chromatography coupled to inductively coupled
      plasma-mass spectrometry (HPLC/ICP-MS) in combination with on-line isotope
      dilution (on-line ID), while structural elucidation of the species was performed
      using HPLC coupled to electrospray ionization-mass spectrometry. The ICP-MS-based
      method developed shows a good intra- and inter-day reproducibility (relative
      standard deviation = 3.5%, N = 9); the limit of detection (1.5 mg TMC207 L(-1))
      is of the same order of magnitude as that for HPLC/radiodetection; the dynamic
      range of the method covers more than two orders of magnitude. Furthermore, the
      column recovery was demonstrated to be quantitative (recoveries between 90.6% and
      99.5%). Based on the excellent figures of merit, the "cold" HPLC/ICP-MS approach
      could be deployed for the actual human in vivo metabolism study, such that
      exposure of the human volunteers to the (14)C radiolabel was avoided.

PMID- 21877186
TI  - Cancer, pre-cancer and normal oral cells distinguished by dielectrophoresis.
AB  - Most oral cancers are oral squamous cell carcinomas (OSCC) that arise from the
      epithelial lining of the oral mucosa. Given that the oral cavity is easily
      accessible, the disease lends itself to early detection; however, most oral
      cancers are diagnosed at a late stage, and approximately half of oral cancer
      sufferers do not survive beyond five years, post-diagnosis. The low survival rate
      has been attributed to late detection, but there is no accepted, reliable and
      convenient method for the detection of oral cancer and oral pre-cancer.
      Dielectrophoresis (DEP) is a label-free technique which can be used to obtain
      multi-parametric measurements of cell electrical properties. Parameters such as
      cytoplasmic conductivity and effective membrane capacitance (C(Eff)) can be non
      invasively determined by the technique. In this study, a novel lab-on-a-chip
      device was used to determine the cytoplasmic conductivity and C(Eff) of primary
      normal oral keratinocytes, and pre-cancerous and cancerous oral keratinocyte cell
      lines. Our results show that the electrical properties of normal, pre-cancerous
      and cancerous oral keratinocytes are distinct. Furthermore, increasing C (Eff)
      and decreasing cytoplasmic conductivity correlate with disease progression which
      could prove significant for diagnostic and prognostic applications. DEP has the
      potential to be used as a non-invasive technique to detect oral cancer and oral
      pre-cancer. Clinical investigation is needed to establish the reliability and
      temporal relationship of the correlation between oncologic disease progression
      and the electrical parameters identified in this study. To use this technique as
      an OSCC detection tool in a clinical setting, further characterisation and
      refinement is warranted.

PMID- 21877187
TI  - Separation of inorganic anions on hydrophobic stationary phases in ion
      chromatography.
AB  - Inorganic anions were separated on hydrophobic stationary phases such as
      triacontyl-functionalized silica. Eluent conditions were examined in detail, and
      iodate, nitrate, iodide, and thiocyanate could be separated by using aqueous
      solutions. The effect of the eluent concentration on the retention of analyte
      anions was examined for a wide range of sodium sulfate concentrations of up to 1
      M. The retention factor of hydrophobic anions decreased with increasing sodium
      sulfate concentration in the lower concentration region, while it increased with
      increasing sodium sulfate concentration in the higher concentration region. The
      addition of a small amount of an organic substance such as acetonitrile and
      tetraethylene glycol increased the retention of iodide and thiocyanate, while the
      addition of alcohols decreased their retention. Operating at lower temperature
      also increased the retention of analyte anions. It was expected that inorganic
      anions were retained on the stationary phase via hydrophobic interactions. The
      retention mechanism was discussed, considering the results obtained.

PMID- 21877188
TI  - Development of an amperometric sulfite biosensor based on a gold
      nanoparticles/chitosan/multiwalled carbon nanotubes/polyaniline-modified gold
      electrode.
AB  - A sulfite oxidase (SOx) purified from leaves of Syzygium cumini (Jamun) was
      immobilized covalently onto a gold nanoparticles (AuNPs)/chitosan
      (CHIT)/carboxylated multiwalled carbon nanotubes (cMWCNTs)/polyaniline (PANI)
      composite that was electrodeposited onto the surface of a gold (Au) electrode. A
      novel and highly sensitive sulfite biosensor was developed that used this enzyme
      electrode (SOx/AuNPs/CHIT/cMWCNT/PANI/Au) as the working electrode, Ag/AgCl as
      the standard electrode, and Pt wire as the auxiliary electrode. The modified
      electrode was characterized by Fourier transform infrared (FTIR) spectroscopy,
      cyclic voltammetry (CV), scanning electron microscopy (SEM), and electrochemical
      impedance spectroscopy (EIS) before and after the immobilization of the SOx. The
      sensor produced its optimum response within 3 s when operated at 50 mVs(-1) in
      0.1 M phosphate buffer, pH 7.0, and at 35  degrees C. The linear range and
      detection limit of the sensor were 0.75-400 MUM and 0.5 MUM (S/N = 3),
      respectively. The biosensor was employed to determine sulfite levels in fruit
      juices and alcoholic beverages. The enzyme electrode was used 300 times over a
      period of three months when stored at 4  degrees C.

PMID- 21877189
TI  - Anti-inflammatory action of sulfated glucosamine on cytokine regulation in LPS
      activated PMA-differentiated THP-1 macrophages.
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of sulfated
      glucosamine (SGlc) on the regulation of inflammatory cytokines and profiles
      involved in immunological activities. Changes in the inflammatory profiles of
      lipopolysaccharide (LPS)-activated phorbol 12-myristate 13-acetate (PMA)
      differentiated THP-1 macrophage models were investigated following SGlc
      treatment. METHODS: Human THP-1 macrophages were used to evaluate anti
      inflammatory profiles. The cytokine secretion levels were measured by enzyme
      linked immunosorbent assay (ELISA). Effects of SGlc on the regulation of mRNA and
      protein levels were determined using RT-PCR and Western blot analysis. The effect
      of SGlc on the activation of mitogen-activated protein kinases (MAPKs) and NF
      kappaB protein was also determined by Western blot analysis. RESULTS: Treatment
      of THP-1 cells with SGlc inhibited the production of pro-inflammatory cytokines
      such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta and IL-6.
      In addition, SGlc suppressed the mRNA and protein expression levels of
      inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2,
      TNF-alpha, IL-1beta, IL-6, 5-lipoxygenase and cytoplasmic phospholipase A(2) in
      LPS-activated THP-1 macrophages. Furthermore, we confirmed that the LPS-activated
      transcriptions of MAPKs and NF-kappaB were inhibited by SGlc treatment in PMA
      differentiated THP-1 macrophages. CONCLUSION: These results suggest that SGlc can
      be considered as a potential anti-inflammatory supplement.

PMID- 21877190
TI  - Associations between ERAP1 polymorphisms and ankylosing spondylitis
      susceptibility: a meta-analysis.
AB  - OBJECTIVE: The aim of this study was to determine whether five polymorphisms of
      endoplasmic reticulum aminopeptidase 1 (ERAP1) confer susceptibility to
      ankylosing spondylitis (AS). METHODS: The authors conducted five types of meta
      analysis on the associations between the rs27044, rs17482078, rs10050860,
      rs30187, and rs2287987 polymorphisms of ERAP1 and AS susceptibility, using fixed
      and random effects models. RESULTS: Six studies were included in this meta
      analysis, which in total involved 4,594 AS patients and 3,971 controls, five
      European populations, and one Asian population. Meta-analysis identified a
      significant association between AS and the two alleles of the rs27044
      polymorphism in all study subjects [odds ratio (OR) = 1.333, 95% confidence
      interval (CI) = 1.102-1.612, p = 0.003]. Stratification by ethnicity identified a
      significant association between this polymorphism and AS in Europeans (OR =
      1.281, 95% CI = 1.032-1.588, p = 0.024) and in Asians (OR = 1.554, 95% CI = 1.313
      1.838, p = 2 * 10(-8)), and meta-analysis of the rs30187 polymorphism showed the
      same pattern. Furthermore, analysis revealed significant associations between the
      two alleles of the rs17482078, rs10050860, and rs2287987 polymorphisms and the
      risk of developing AS in Europeans (OR = 0.726, 95% CI = 0.655-0.805, p < 1 * 10(
      10); OR = 0.724, 95% CI = 0.665-0.787, p < 1 * 10(-10); OR = 0.708, 95% CI =
      0.639-0.784, p < 1 * 10(-10), respectively). However, the single Asian study
      included showed no association between the rs17482078, rs30187, and rs2287987
      polymorphisms and AS. CONCLUSIONS: This meta-analysis shows that the rs27044,
      rs17482078, rs10050860, rs30187, and rs2287987 polymorphisms of ERAP1 are
      associated with the development of AS in Europeans. However, further study of
      this association is required in other ethnic groups.

PMID- 21877191
TI  - Comparative study of two materials for dynamic hip screw during fall and gait
      loading: titanium alloy and stainless steel.
AB  - BACKGROUND: Internal fixation with dynamic hip screw is a choice of treatment for
      hip fractures to stabilize a femoral fracture. Choosing the proper implant and
      its material has a great effect on the healing process and failure prevention.
      The purpose of this analysis was to assess biomechanical behavior of dynamic hip
      screw with two different materials implanted in the femur during fall and gait.
      METHODS: A 3D finite element model of an intact femur and a 3D implant within the
      same femur were developed. A finite element analysis was carried out to establish
      the effect of load conditions and implant material properties on biomechanical
      behavior of the dynamic hip screw after internal fixation. Two load
      configurations are chosen: one simulating the stance phase of the normal gait
      cycle, and the other replicating a low-energy fall. The implanted femur was
      investigated with two different materials for the dynamic hip screw: stainless
      steel and titanium alloy. RESULTS: During stance, more stress is placed on the
      implanted femur compared with the intact femur. During a fall, the implanted
      femur is in a greater state of stress, which mostly occurs inside the dynamic hip
      screw. Titanium alloy decreases stress levels by an average of 40% compared with
      stainless steel. However, deformation is slightly reduced with a stainless steel
      dynamic hip screw during both load cases. CONCLUSIONS: After internal fixation,
      dynamic hip screw generates greater stresses within the implanted femur compared
      with the intact femur under the same loading conditions. A titanium alloy implant
      appears to undergo less stress from a low-energy fall compared with stainless
      steel and can be considered the preferred implant material. The critical parts of
      the dynamic hip screw are the forth distal screw and the plate.

PMID- 21877192
TI  - Hypotonic challenge modulates cell volumes differently in the superficial zone of
      intact articular cartilage and cartilage explant.
AB  - The objective of this study was to evaluate the effect of sample preparation on
      the biomechanical behaviour of chondrocytes. We compared the volumetric and
      dimensional changes of chondrocytes in the superficial zone (SZ) of intact
      articular cartilage and cartilage explant before and after a hypotonic challenge.
      Calcein-AM labelled SZ chondrocytes were imaged with confocal laser scanning
      microscopy through intact cartilage surfaces and through cut surfaces of
      cartilage explants. In order to clarify the effect of tissue composition on cell
      volume changes, Fourier Transform Infrared microspectroscopy was used for
      estimating the proteoglycan and collagen contents of the samples. In the isotonic
      medium (300 mOsm), there was a significant difference (p < 0.05) in the SZ cell
      volumes and aspect ratios between intact cartilage samples and cartilage
      explants. Changes in cell volumes at both short-term (2 min) and long-term (2 h)
      time points after the hypotonic challenge (180 mOsm) were significantly different
      (p < 0.05) between the groups. Further, proteoglycan content was found to
      correlate significantly (r(2) = 0.63, p < 0.05) with the cell volume changes in
      cartilage samples with intact surfaces. Collagen content did not correlate with
      cell volume changes. The results suggest that the biomechanical behaviour of
      chondrocytes following osmotic challenge is different in intact cartilage and in
      cartilage explant. This indicates that the mechanobiological responses of
      cartilage and cell signalling may be significantly dependent on the integrity of
      the mechanical environment of chondrocytes.

PMID- 21877194
TI  - Leptin and breast cancer: an overview.
AB  - Leptin is a well-known mediator of obesity. Leptin and its receptor are
      overexpressed in breast cancer, especially in high-grade tumors. It has an
      association with progression and poor survival of breast cancer. Leptin can
      regulate endothelial cell proliferation and promote angiogenesis. There are
      several other factors such as insulin and HER2 may be involved in the
      relationship between leptin and breast cancer. Leptin system has emerged as a new
      and promising therapeutic target for breast cancer. This review article
      summarizes the current knowledge about the relation of leptin and breast cancer.

PMID- 21877195
TI  - Serum neuron-specific enolase is correlated with clinical outcome of patients
      with non-germinal center B cell-like subtype of diffuse large B-cell lymphoma
      treated with rituximab-based immunochemotherapy.
AB  - The present study examines the clinical significance of serum neuron-specific
      enolase (NSE) in patients with non-germinal center B-cell type (non-GCB) of
      diffuse large B-cell lymphoma (DLBCL) that received rituximab chemotherapy. Serum
      NSE values were measured using electrochemiluminescence assay in 53 patients.
      About 54.7% of the DLBCL patients had positive expression of serum NSE (>15.20
      ng/ml), which closely correlated with performance status, serum LDH level, B
      symptoms, IPI scores, and Ann-Arbor stages (P < 0.05). The mean serum NSE value
      in patients with non-GCB subtype of DLBCL was significantly higher than that of
      GCB subtype of DLBCL (P = 0.001), and among patients in non-GCB subtype group,
      there was significant difference in the 5-year OS rate between NSE-positive group
      and negative group (28.3% vs. 81.6%, P < 0.001). Furthermore, serum NSE level was
      found to be an independent prognostic factor in patients with non-GCB subtype.
      Serum NSE may be a novel marker of disease aggressiveness as well as a prognostic
      factor for non-GCB subtype of DLBCL in the era of rituximab.

PMID- 21877196
TI  - Possible association of NAT2 polymorphism with laryngeal cancer risk: an evidence
      based meta-analysis.
AB  - PURPOSE: N-acetyltransferase 2 (NAT2) plays an important role in the metabolism
      of various potential carcinogens, which can be subdivided into rapid and slow
      acetylation phenotype according to the different genotypes. A number of studies
      have been devoted to the association of NAT2 polymorphism with susceptibility to
      laryngeal carcinoma; however, the results were inconsistent and inconclusive. The
      aim of the present study was to conduct a meta-analysis assessing the possible
      association of NAT2 polymorphism with laryngeal cancer risk. METHODS: The
      relevant studies were identified through a search of PubMed, Embase, ISI Web of
      Knowledge, and Chinese National Knowledge Infrastructure until February 2011 and
      selected on the basis of the established inclusion criteria for publications, and
      then a meta-analysis was performed to quantitatively summarize the association of
      NAT2 polymorphism with laryngeal cancer susceptibility. RESULTS: Seven studies
      were included in the present meta-analysis, which described a total of 980
      laryngeal cancer cases and 1,487 controls. The overall odds ratio (OR) for NAT2
      slow and rapid acetylators was 0.99 (95% CI = 0.71-1.38) and 1.01 (95% CI = 0.72
      1.40), respectively. When stratifying for race, the pooled ORs for NAT2 slow
      acetylator were 1.99 (95% CI = 1.10-3.63) in Asians and 0.85 (95% CI = 0.62-1.15)
      in Caucasians, and the pooled ORs for NAT2 rapid acetylator were 0.50 (95% CI =
      0.28-0.91) in Asians and 1.18 (95% CI = 0.87-1.60) in Caucasians. CONCLUSIONS:
      This meta-analysis suggested that there was overall lack of association between
      NAT2 polymorphism and laryngeal cancer risk; however, NAT2 slow acetylation may
      contribute to a risk factor for laryngeal cancer in Asians but not in Caucasians.

PMID- 21877197
TI  - Redox regulation of cytokeratin 18 protein by NADPH oxidase 1 in preneoplastic
      human epithelial cells.
AB  - INTRODUCTION: A catalytic subunit of NADPH oxidase 1 (Nox1) is implicated to be
      involved in neoplastic progression in human epithelial cancers. We had previously
      demonstrated that Nox1 overexpression of immortalized epithelial cells was able
      to induce the generation of progenitor cells that expressed fetal-type
      cytokeratins 8 and 18. PURPOSE: We aimed to investigate the direct effects and
      underlying mechanisms of Nox1 on expression of cytokeratin 18 (CK18). METHODS:
      Immortalized human epithelial GM16 cells with low CK18 were used in Nox1
      overexpression experiments. NuB2 cells with high CK18 were used in Nox1 knockdown
      experiments. Protein expression of CK18, phosphorylated and ubiquitinated CK18
      were analyzed by Western blot. RESULTS: With no effects on the mRNA levels, CK18
      protein was increased upon Nox1 overexpression and decreased upon Nox1 knockdown.
      Treatment with proteasome inhibitor MG132 prevented CK18 degradation and
      increased CK18 protein indicating translational regulation of CK18. Treatment for
      NuB2 cells with N-acetyl-L: -cysteine, diphenyleneiodonium, or apocynin decreased
      CK18 protein levels indicating its regulation involving reactive oxygen species
      and flavoprotein Nox. It has been known that phosphorylation of CK18 regulates
      CK18 turnover by ubiquination. Consistently, Nox1 modulated CK18 phosphorylation
      at ser52. Nox1 knockdown and treatment with diphenyleneiodonium accumulated the
      levels of ubiquinated CK18 enhancing degradation causing decreased CK18 protein.
      CONCLUSION: We demonstrated that Nox1 was able to induce CK18 stabilization by
      inhibiting CK18 protein degradation in a phosphorylation-dependent manner. CK18
      accumulation induced by Nox1 is consistent with the persistence of fetal-type
      CK18 protein in many epithelial carcinomas.

PMID- 21877198
TI  - The CDK inhibitors in cancer research and therapy.
AB  - Chemical compounds that interfere with an enzymatic function of kinases are
      useful for gaining insight into the complicated biochemical processes in
      mammalian cells. Cyclin-dependent kinases (CDK) play an essential role in the
      control of the cell cycle and/or proliferation. These kinases as well as their
      regulators are frequently deregulated in different human tumors. Aberrations in
      CDK activity have also been observed in viral infections, Alzheimer's,
      Parkinson's diseases, ischemia and some proliferative disorders. This led to an
      intensive search for small-molecule CDK inhibitors not only for research
      purposes, but also for therapeutic applications. Here, we discuss seventeen CDK
      inhibitors and their use in cancer research or therapy. This review should help
      researchers to decide which inhibitor is best suited for the specific purpose of
      their research. For this purpose, the targets, commercial availability and IC(50)
      values are provided for each inhibitor. The review will also provide an overview
      of the clinical studies performed with some of these inhibitors.

PMID- 21877199
TI  - The effects of adiponectin and leptin on changes in bone mineral density.
AB  - We tested the hypothesis that low leptin and high adiponectin levels are
      associated with higher rates of bone mineral density (BMD) loss among 3,075 men
      and women, aged 70-79, from the Health Aging and Body Composition Study. Results
      suggest that adiponectin, but not leptin, is a risk factor for bone loss in
      women. INTRODUCTION: Adiponectin and leptin are hormones secreted by adipose
      cells that may impact BMD. Few studies have evaluated the longitudinal
      association of leptin and adiponectin levels with rates of BMD change. METHODS:
      Hip and whole-body areal BMD (aBMD) were measured five times using dual-energy X
      ray absorptiometry over 10 years (average follow-up time, 7.95 +/- 1.92 years).
      Trabecular lumbar spine volumetric BMD (vBMD) was measured using quantitative
      computed topography at baseline and year 6 in the Pittsburgh cohort only. Random
      slope and intercept models were used to account for within person correlation as
      a result of repeated measures of hip and whole-body aBMD. Linear regression was
      used to model changes in spine trabecular vBMD. RESULTS: Among women, the
      annualized rate of hip aBMD loss in the highest tertile of adiponectin was -0.67%
      (95% CI -0.77, -0.58) compared to [-0.43% (95% CI -0.51, -0.35)] in the lowest
      tertile (p trend = 0.019) after adjusting for age, race, BMI, diabetes, baseline
      hip aBMD, and weight change. In men, hip aBMD loss was greatest in the high
      adiponectin group (tertile 3), however this association was not significant (p
      trend = 0.148). After adjusting for weight change in women, the association
      between higher leptin and lower hip aBMD loss was attenuated and no longer
      significant (p trend = 0.134). Leptin and adiponectin levels were not associated
      with whole-body aBMD or trabecular lumbar spine vBMD loss. CONCLUSIONS:
      Adiponectin was associated with increased hip aBMD loss in women only, supporting
      evidence that adiponectin may have an important role in bone health.

PMID- 21877200
TI  - Soluble fatty acid synthase relates to bone biomarkers in prepubertal children.
AB  - SUMMARY: Circulating soluble fatty acid synthase (FASN, a key enzyme in de novo
      biosynthesis of fatty acids, expressed in both adipocytes and osteoblasts) is
      clinically related to a less favorable bone profile in healthy prepubertal
      children. Soluble FASN may participate in the reciprocal regulation between fat
      and bone metabolism. INTRODUCTION: Fatty acid synthase (FASN), a key enzyme in de
      novo biosynthesis of fatty acids, is expressed in adipocytes and osteoblasts. We
      hypothesized that FASN may participate in the crosstalk between fat and bone. To
      this aim, we studied the relation between circulating soluble FASN (an
      extracellular FASN that reflects previously intracellular enzymatic activity) and
      adipose tissue and bone biomarkers in prepubertal children. METHODS: Circulating
      soluble FASN, total and high molecular weight (HMW) adiponectin, bone biomarkers
      [osteocalcin (OC), uncarboxylated osteocalcin (ucOC), C-terminal cross-linked
      telopeptide of type I collagen (CTX), bone-specific alkaline phosphatase (BSAP)],
      and a profile of energy metabolism [body fat, insulin resistance and secretion
      (HOMA), serum lipids] were assessed in 84 asymptomatic prepubertal children (44
      girls, 40 boys, age 6.8 +/- 0.1 year). Serum 25-OH Vitamin D (Vit D) was
      additionally measured. RESULTS: Circulating soluble FASN increased with
      increasing HMW adiponectin (r = 0.29, p = 0.01) and decreasing serum Vit D (r = 
      0.21, p < 0.05), and was related to a less favorable bone profile, showing
      negative associations with bone-derived metabolic parameters [total OC (r = 
      0.33, p = 0.002) and ucOC (r = -0.37, p < 0.0001)] and a positive association
      with the CTX-to-BSAP ratio (r = 0.31, p < 0.01). These correlations were not
      explained by age, gender, body fat, insulin resistance or secretion or serum
      lipids; however, they were predominant in those subjects with Vit D levels below
      the population median. CONCLUSIONS: Circulating soluble FASN relates to both
      adipose tissue and bone biomarkers in prepubertal children, with associations
      that are dependent on Vit D concentrations. These findings suggest that FASN may
      participate in the crosstalk between fat and bone metabolism.

PMID- 21877201
TI  - Patients with cirrhosis and ascites have false values of bone density:
      implications for the diagnosis of osteoporosis.
AB  - The effect of ascites on bone densitometry has been assessed in 25 patients with
      advanced cirrhosis, and it was concluded that ascites over 4 l causes inaccuracy
      of BMD measurements, particularly at the lumbar spine. This fact must be
      considered when assessing bone mass in patients with decompensated cirrhosis.
      INTRODUCTION: Bone mineral density (BMD) measured by dual-energy x-ray
      absorptiometry (DXA) is the best procedure for assessment of osteoporosis and
      fracture risk, but BMD values at the central skeleton may be influenced by
      changes in soft tissues. Therefore, we have studied the effect of ascites on BMD.
      METHODS: BMD was measured by DXA at the lumbar spine, femoral neck and total hip,
      just before and shortly after therapeutic paracentesis in 25 patients with
      advanced liver cirrhosis. Changes in BMD, lean and fat mass, abdominal diameter
      and weight, as well as the amount of removed ascites were measured. RESULTS: The
      amount of drained ascites was 6.6 +/- 0.5 l (range: 3.0 to 12.7 l). After
      paracentesis, BMD increased at the lumbar spine (from 0.944 +/- 0.035 to 0.997 +/
      0.038 g/cm(2), p < 0.001) and at the total hip (from 0.913 +/- 0.036 to 0.926 +/
      0.036 g/cm(2), p < 0.01). Patients with a volume of drained ascites higher than
      4 l showed a significant increase in lumbar BMD (7.0%), compared with patients
      with a lower amount (1.5%) (p < 0.03). The decrease in total soft tissue mass
      correlated with the amount of removed ascites (r = 0.951, p < 0.001). Diagnosis
      of osteoporosis or osteopenia changed after paracentesis in 12% of patients.
      CONCLUSION: Ascites over 4 l causes inaccuracy of BMD measurements, particularly
      at the lumbar spine. This fact must be considered when assessing bone mass in
      patients with advanced cirrhosis.

PMID- 21877202
TI  - Secular trends of hip fractures in Quebec, Canada.
AB  - This study examined the secular trends of hip fracture incidence among
      individuals 50 years and older in Quebec between 1993 and 2004. Age-standardized
      rates decreased at both the provincial and regional levels. The largest relative
      decrease was observed among younger females, and rates declined more slowly in
      the elderly. INTRODUCTION: The population of the province of Quebec is among the
      oldest in North America. Before the trend rupture reported in the late 1990s in
      several countries, hip fracture (HF) incidence rates did not show a secular trend
      (between 1981 and 1992). This study examined the secular trends of HF incidence
      at the provincial level and in two of the most important urban areas of the
      province, Montreal and Quebec City, between 1993 and 2004. METHODS: All
      hospitalisations of individuals 50 years and older living in the province of
      Quebec between 1993 and 2004 with a main diagnosis of HF were included.
      Standardized rates of HF incidence were calculated for females and males, 50-74
      years and 75 years and older. RESULTS: The Quebec City area showed a strong
      decreasing trend in HF rates for younger females, but the other groups did not
      show an obvious trend. Although our models did not support the existence of
      significant differences in trends between both areas, the rates of HF of younger
      males and, to a lesser extent, of older women in the Montreal area were
      significantly higher than in the Quebec City area. CONCLUSIONS: Differences
      observed in hip fracture rates as well as in secular trends between age groups
      and gender emphasise the need for decision makers to rely on results based on age
      specific and sex-specific analyses.

PMID- 21877203
TI  - Predicting product adherence in a topical microbicide safety trial in Pune,
      India.
AB  - The inconclusive results of past trials and recent findings of partial protection
      of Tenofovir 1% gel underscore the need to better understand product adherence in
      microbicide trials. This study aimed to identify factors predicting couples'
      ability to sustain topical gel and condom use during clinical trial
      participation. We enrolled 100 Indian participants of a randomized, controlled
      safety trial of Tenofovir 1% gel (CT cohort) and 100 similar women who were
      ineligible or declined trial participation (NCT cohort). Compared to the NCT
      cohort, CT women reported higher baseline condom use, more positive attitudes
      towards condoms and higher levels of protection efficacy. While NCT condom use
      remained low, CT condom use increased dramatically during the study. Reported gel
      consistency was higher than condom consistency. Individual and couple-related
      factors predicted condom consistency and interest in future gel use, but not gel
      consistency. Findings could inform trial recruitment strategies and product
      introduction.

PMID- 21877204
TI  - Performances on the CogState and standard neuropsychological batteries among HIV
      patients without dementia.
AB  - HIV-associated neurocognitive disorders remain prevalent but challenging to
      diagnose particularly among non-demented individuals. To determine whether a
      brief computerized battery correlates with formal neurocognitive testing, we
      identified 46 HIV-infected persons who had undergone both formal neurocognitive
      testing and a brief computerized battery. Simple detection tests correlated best
      with formal neuropsychological testing. By multivariable regression model, 53% of
      the variance in the composite Global Deficit Score was accounted for by elements
      from the brief computerized tool (P < 0.01). These data confirm previous
      correlation data with the computerized battery. Using the five significant
      parameters from the regression model in a Receiver Operating Characteristic
      curve, 90% of persons were accurately classified as being cognitively impaired or
      not. The test battery requires additional evaluation, specifically for
      identifying persons with mild impairment, a state upon which interventions may be
      effective.

PMID- 21877205
TI  - Probing for consciousness after severe brain injury by functional magnetic
      resonance imaging (fMRI).

PMID- 21877206
TI  - Distribution of white matter hyperintensity in cerebral hemorrhage and healthy
      aging.
AB  - We compared the severity of white matter T2-hyperintensities (WMH) in the frontal
      lobe and occipital lobe using a visual MRI score in 102 patients with lobar
      intracerebral hemorrhage (ICH) diagnosed with possible or probable cerebral
      amyloid angiopathy (CAA), 99 patients with hypertension-related deep ICH, and 159
      normal elderly subjects from a population-based cohort. The frontal-occipital
      (FO) gradient was used to describe the difference in the severity of WMH between
      the frontal lobe and occipital lobe. A higher proportion of subjects with obvious
      occipital dominant WMH (FO gradient <=-2) was found among patients with lobar ICH
      than among healthy elderly subjects (FO gradient <=-2: 13.7 vs. 5.7%, p = 0.03).
      Subjects with obvious occipital dominant WMH were more likely to have more WMH (p
      = 0.0006) and a significantly higher prevalence of the apolipoprotein E epsilon4
      allele (45.8% vs. 19.4%, p = 0.04) than those who had obvious frontal dominant
      WMH. This finding is consistent with the relative predilection of CAA for
      posterior brain regions, and suggests that white matter lesions may
      preferentially occur in areas of greatest vascular pathology.

PMID- 21877207
TI  - The effect of thrombolysis on short-term improvement depends on initial stroke
      severity.
AB  - A large number of parameters have been identified as predictors of early outcome
      in patients with acute ischemic stroke. In the present work we analyzed a wide
      range of demographic, metabolic, physiological, clinical, laboratory and
      neuroimaging parameters in a large population of consecutive patients with acute
      ischemic stroke with the aim of identifying independent predictors of the early
      clinical course. We used prospectively collected data from the Acute Stroke
      Registry and Analysis of Lausanne. All consecutive patients with ischemic stroke
      admitted to our stroke unit and/or intensive care unit between 1 January 2003 and
      12 December 2008 within 24 h after last-well time were analyzed. Univariate and
      multivariate analyses were performed to identify significant associations with
      the National Institute of Health Stroke Scale (NIHSS) score at admission and 24 h
      later. We also sought any interactions between the identified predictors. Of the
      1,730 consecutive patients with acute ischemic stroke who were included in the
      analysis, 260 (15.0%) were thrombolyzed (mostly intravenously) within the
      recommended time window. In multivariate analysis, the NIHSS score at 24 h after
      admission was associated with the NIHSS score at admission (beta = 1, p < 0.001),
      initial glucose level (beta = 0.05, p < 0.002) and thrombolytic intervention
      (beta = -2.91, p < 0.001). There was a significant interaction between
      thrombolysis and the NIHSS score at admission (p < 0.001), indicating that the
      short-term effect of thrombolysis decreases with increasing initial stroke
      severity. Thrombolytic treatment, lower initial glucose level and lower initial
      stroke severity predict a favorable early clinical course. The short-term effect
      of thrombolysis appears mainly in minor and moderate strokes, and decreases with
      increasing initial stroke severity.

PMID- 21877208
TI  - Detection of bat coronaviruses from Miniopterus fuliginosus in Japan.
AB  - Bats have great potential as reservoirs for emerging viruses such as severe acute
      respiratory syndrome-coronavirus. In this study, bat coronaviruses (BtCoVs) were
      detected by RT-PCR from intestinal and fecal specimens of Miniopterus fuliginosus
      breeding colonies in Wakayama Prefecture caves, where we previously identified
      bat betaherpesvirus 2. Two primer sets were used for the detection of BtCoV: one
      was for the RNA-dependent RNA polymerase (RdRp) region and the other was for the
      spike (S) protein region. Eleven and 73% of intestinal and fecal specimens,
      respectively, were positive for RdRp region, and 2 and 40% of those were positive
      for S protein region. Sequencing and phylogenetic analysis showed that the
      detected BtCoV belonged to the group 1 (alpha) coronaviruses. These data suggest
      that BtCoV is endemic in M. fuliginosus in Japan.

PMID- 21877209
TI  - Focus group study assessing self-management skills of Chinese Americans with type
      2 diabetes mellitus.
AB  - Despite a rapid growth of Type 2 diabetes mellitus in Chinese Americans, the
      management of diabetes in this population is yet understudied. This pilot study
      attempts a first step in seeking solutions to decrease demand for health services
      in this population by improving patients' self-care. Focus groups were conducted
      in well-controlled (HbA1c < 7) and poorly-controlled (HbA1c > 8) Chinese
      Americans with Type 2 DM who were asked about their knowledge and self-care
      skills of diabetes as well as experience of living with the disease. Well
      controlled had more insights in their illness and were more inquisitive, while
      poorly-controlled were more fixated on symptoms and side effects of treatments.
      Common themes for both groups included interest in diet and Traditional Chinese
      Medicine. The findings provide valuable information to design a survey instrument
      to more definitively assess self-care skills differentiating levels of control,
      suggest that changing attitudes and behaviors need to be a stronger focus in care
      and identify needs to provide more culturally appropriate materials to care for
      this population.

PMID- 21877210
TI  - Ventilator-associated pneumonia in children after cardiac surgery in The
      Netherlands.
AB  - PURPOSE: We conducted a retrospective cohort study in an academic tertiary care
      center to characterize ventilator-associated pneumonia (VAP) in pediatric
      patients after cardiac surgery in The Netherlands. METHODS: All patients
      following cardiac surgery and mechanically ventilated for >=24 h were included.
      The primary outcome was development of VAP. Secondary outcomes were duration of
      mechanical ventilation and length of ICU stay. RESULTS: A total of 125 patients
      were enrolled. Their mean age was 16.5 months. The rate of VAP was 17.1/1,000
      mechanical ventilation days. Frequently found organisms were Haemophilus
      influenzae, Moraxella catarrhalis, Staphylococcus aureus and Pseudomonas
      aeruginosa. Patients with VAP had longer duration of ventilation and longer ICU
      stay. Risk factors associated with the development of VAP were a PRISM III score
      of >=10 and transfusion of fresh frozen plasma. CONCLUSION: The mean VAP rate in
      this population is higher than that reported in general pediatric ICU
      populations. Children with VAP had a prolonged need for mechanical ventilation
      and a longer ICU stay.

PMID- 21877211
TI  - Withholding or withdrawing therapy in intensive care units: an analysis of
      collaboration among healthcare professionals.
AB  - PURPOSE: The purpose of the study was to determine the views of intensive care
      nurses, intensivists, and primary physicians regarding collaboration and other
      aspects of withholding and withdrawing therapy in the intensive care unit (ICU).
      METHODS: A questionnaire survey was conducted in seven hospitals in the Region of
      Southern Denmark, including six regional and four university ICUs. Four hundred
      ninety-five nurses, 135 intensivists, and 146 primary physicians participated in
      the study. The primary physicians came from two regional hospitals. RESULTS: The
      unified response rate was 84%. "Futile therapy" and "Patient's wish" were for all
      participants the main reasons for considering withholding or withdrawing therapy.
      Of primary physicians 63% found their general experience of collaboration very or
      extremely satisfactory compared to 36% of intensivists and 27% of nurses. Forty
      three percent of nurses, 29% of intensivists, and 2% of primary physicians found
      that decisions regarding withdrawal of therapy were often, very often, or always
      unnecessarily postponed. Intensivists with ICU as their main workplace were more
      satisfied with the collaboration and more rarely found that end-of-life decisions
      were changed or postponed compared to intensivists who did not have ICU as their
      main workplace. CONCLUSION: Nurses, intensivists and primary physicians differ in
      their perception of collaboration and other aspects of withholding and
      withdrawing therapy practises at the ICU. Multi-disciplinary patient conferences,
      nurse involvement in the decision-making process, and guidelines for withholding
      and withdrawing therapy are recommended.

PMID- 21877212
TI  - Consistency between guidelines and reported practice for reducing the risk of
      catheter-related infection in British paediatric intensive care units.
AB  - PURPOSE: Optimal strategies for reducing catheter-related blood stream infection
      (CR-BSI) differ for adults and children. National guidelines do not make child
      specific recommendations. We determined whether evidence explained the
      inconsistencies between guidelines and reported practice in paediatric intensive
      care units (PICUs). METHODS: We conducted a survey of eight interventions for
      reducing CR-BSI in all 25 British PICUs in 2009. Interventions were categorised
      as requiring child-specific evidence, generalisable to adults and children, or
      organisational recommendations. RESULTS: Twenty-four of the 25 PICUs responded.
      For child-specific interventions, practice diverged from guidelines for "Insert
      into subclavian/jugular veins" (18 PICUs frequently used femoral veins, supported
      by observational evidence for increased safety in children). Practice reflected
      guidelines for "Use standard but consider antimicrobial-impregnated central
      venous catheters (CVCs) for high-risk patients" (14 used standard only, 3 used
      standard and antimicrobial-impregnated despite no randomised controlled trial
      (RCT) evidence for antimicrobial-impregnated CVCs in children, 7 used heparin
      bonded for some or all children); "Use 2% chlorhexidine for skin preparation" (20
      PICUs); "Avoid routine CVC replacement" (20 PICUs). For generalisable
      interventions, practice was consistent with guidelines for "Administration set
      replacement" (21 PICUs) but deviated for "Maintenance of CVC asepsis" (11 PICUs
      used alcohol due to inconclusive evidence for chlorhexidine). Practice diverged
      from guidelines for organisational interventions: "Train healthcare workers in
      CVC care" (9 PICUs); "Monitor blood stream infection (BSI) rates" (8 PICUs).
      CONCLUSIONS: Guidelines should explicitly address paediatric practice and report
      the quality of evidence and strength of recommendations. Organisations should
      ensure doctors are trained in CVC insertion and invest in BSI monitoring,
      especially in PICUs. The type of CVC and insertion site are important gaps in
      evidence for children.

PMID- 21877213
TI  - Genes of intestinal Escherichia coli and their relation to the inflammatory
      activity in patients with ulcerative colitis and Crohn's disease.
AB  - Escherichia coli gene fimA was the most frequent gene that occurred in the
      intestine of all investigated groups. All subjects with fimA gene had
      significantly higher values of tumor necrosis factor alpha (TNF-alpha) and CRP
      than those with other E. coli genes. There was also a tendency to increased serum
      interleukin (IL)-6 levels in patients carrying the fimA gene; however, no
      relation was observed to serum IL-8 and IL-10. Patients with Crohn's disease had
      significantly higher IL-6 than those with ulcerative colitis (UC) and controls.
      The highest levels of TNF-alpha were detected in the UC group. There were no
      significant differences in serum IL-8 and IL-10 between all three groups. The
      presence of E. coli gene fimA in the large bowel of patients with IBD is related
      to the immunological activity of the disease which may be important from the
      aspect of therapeutical strategy.

PMID- 21877215
TI  - Perturbation of intracellular K(+) homeostasis with valinomycin promotes cell
      death by mitochondrial swelling and autophagic processes.
AB  - Perturbation of cellular K(+) homeostasis is a common motif in apoptosis but it
      is unknown whether a decrease in intracellular K(+) alone is sufficient to
      replicate apoptotic hallmarks. We investigated, which mode of cell death is
      induced by decreasing the intracellular K(+) concentration using valinomycin, a
      highly K(+)-selective ionophore. Valinomycin treatment induced mitochondrial
      swelling and minor nuclear changes in cell lines (BV-2, C6, HEK 293), and in
      primary mouse microglia and astrocytes. In the microglial cell line BV-2, we
      identified and quantified three phenotypes in valinomycin-exposed cells. The
      first and most prevalent phenotype (62 +/- 2%) was characterized by swollen
      mitochondria and no chromatin condensation, and the second (25 +/- 3%) by swollen
      mitochondria and slight chromatin condensation. Only the third phenotype (11 +/-
      4%) fulfilled criteria of apoptosis by having normal-sized mitochondria and
      strongly condensed chromatin. Valinomycin-induced swelling of mitochondria was
      not altered by the adenine nucleotide translocase inhibitor bongkrekic acid (BA),
      the pan caspase inhibitor Z-VAD-FMK, changing extracellular K(+) or Cl(-)
      concentrations, or the membrane-permeable Ca(2+) chelator BAPTA-AM. Only co
      exposure of cells to valinomycin and the Ca(2+) ionophore ionomycin in high K(+)
      Cl(-)-free extracellular solution suppressed mitochondrial swelling. Ionomycin
      alone caused shrinkage of mitochondria. Additionally, valinomycin promoted
      autophagic processes, which were further enhanced by preincubation with BA or
      with Z-VAD-FMK. Valinomycin-dependent chromatin condensation was inhibited by BA,
      Z-VAD-FMK, BAPTA-AM, and ionomycin. Our findings demonstrate that mitochondrial
      swelling and autophagy are common features of valinomycin-exposed cells.
      Accordingly, valinomycin promotes an autophagic cell death mode, but not
      apoptosis.

PMID- 21877214
TI  - Heterogeneity of primary glioblastoma cells in the expression of caspase-8 and
      the response to TRAIL-induced apoptosis.
AB  - Recent studies suggest that cancer stem cells (CSCs) are responsible for cancer
      resistance to therapies. We therefore investigated how glioblastoma-derived CSCs
      respond to the treatment of tumor necrosis factor-related apoptosis-inducing
      ligand (TRAIL). Neurospheres were generated from glioblastomas, characterized for
      CSC properties including self-renewal, cell differentiation and xenograft
      formation capacity, and analyzed for TRAIL-induced apoptosis, CASP8 genomic
      status, and caspase-8 protein expression. The neurosphere NSC326 was sensitive to
      TRAIL-induced apoptosis as evidenced by cell death and caspase-8, -3, and -7
      enzymatic activities. In contrast, however, the neurosphere NSC189 was TRAIL
      resistant. G-banding analysis identified five chromosomally distinguishable cell
      populations in the neurospheres. Fluorescence in situ hybridization revealed the
      variation of chromosome 2 copy number in these populations and the loss of CASP8
      locus in 2q33-34 region in a small set of cell populations in the neurosphere.
      Immunohistochemistry of NSC189 cell blocks revealed the lack of caspase-8 protein
      in a subset of neurosphere cells. Western blotting and immunohistochemistry of
      human glioblastoma tumors demonstrated the expression of caspase-8 protein in the
      vast majority of the tumors as compared to normal human brain tissues that lack
      the caspase-8 expression. This study shows heterogeneity of glioblastomas and
      derived CSCs in the genomic status of CASP8, expression of caspase-8, and thus
      responsiveness to TRAIL-induced apoptosis. Clinic trials may consider genomic
      analysis of the cancer tissue to identify the genomic loss of CASP8 and use it as
      a genomic marker to predict the resistance of glioblastomas to TRAIL apoptosis
      pathway-targeted therapies.

PMID- 21877217
TI  - Comparing the use of global rating scale with checklists for the assessment of
      central venous catheterization skills using simulation.
AB  - The use of checklists is recommended for the assessment of competency in central
      venous catheterization (CVC) insertion. To explore the use of a global rating
      scale in the assessment of CVC skills, this study seeks to compare its use with
      two checklists, within the context of a formative examination using simulation.
      Video-recorded performances of CVC insertion by 34 first-year medical residents
      were reviewed by two independent, trained evaluators. Each evaluator used three
      assessment tools: a ten-item checklist, a 21-item checklist, and a nine-item
      global rating scale. Exploratory principal component analysis of the global
      rating scale revealed two factors, accounting for 84.1% of the variance:
      technical ability and safety. The two checklist scores correlated positively with
      the weighted factor score on technical ability (0.49 [95% CI 0.17-0.71] for the
      10-item checklist; 0.43 [95% CI 0.10-0.67] for the 21-item checklist) and
      negatively with the weighted factor score on safety (-0.17 [95% CI -0.48-0.18]
      for the 10-item checklist; -0.13 [95% CI -0.45-0.22] for the 21-item checklist).
      A checklist score of <80% was strong indication of incompetence. However, a high
      checklist score did not preclude incompetence. Ratings using the global rating
      scale identified an additional 11 candidates (32%) who were deemed incompetent
      despite scoring >80% on both checklists. All these candidates committed serious
      errors. In conclusion, the practice of universal adoption of checklists as the
      preferred method of assessment of procedural skills should be questioned. The
      inclusion of global rating scales should be considered.

PMID- 21877216
TI  - Neurologic and psychiatric manifestations of celiac disease and gluten
      sensitivity.
AB  - Celiac Disease (CD) is an immune-mediated disease dependent on gluten (a protein
      present in wheat, rye or barley) that occurs in about 1% of the population and is
      generally characterized by gastrointestinal complaints. More recently the
      understanding and knowledge of gluten sensitivity (GS), has emerged as an illness
      distinct from celiac disease with an estimated prevalence 6 times that of CD.
      Gluten sensitive people do not have villous atrophy or antibodies that are
      present in celiac disease, but rather they can test positive for antibodies to
      gliadin. Both CD and GS may present with a variety of neurologic and psychiatric
      co-morbidities, however, extraintestinal symptoms may be the prime presentation
      in those with GS. However, gluten sensitivity remains undertreated and
      underrecognized as a contributing factor to psychiatric and neurologic
      manifestations. This review focuses on neurologic and psychiatric manifestations
      implicated with gluten sensitivity, reviews the emergence of gluten sensitivity
      distinct from celiac disease, and summarizes the potential mechanisms related to
      this immune reaction.

PMID- 21877218
TI  - [Pericardial effusion. Differential diagnostics, surveillance and treatment].
AB  - Cardiac tamponade can be a life-threatening condition due to the high variability
      of clinical symptoms and the associated risk of rapid hemodynamic deterioration.
      Therefore, accurate diagnosis followed by immediate intervention is necessary.
      Common clinical features of cardiac tamponade are pulsus paradoxus, tachycardia,
      elevated jugular venous pressure and hypotension; however, although these can be
      indicative of cardiac tamponade they are non-specific. Instant confirmation of
      the clinical diagnosis of cardiac tamponade can be pursued with echocardiography
      which also enables a clear estimation of the current hemodynamic situation. Thus
      in contemporary clinical practice echocardiography plays a key role in the
      management of cardiac tamponade and must be consulted with regards to final
      treatment decisions. Common practice includes pericardial puncture under
      echocardiographic and/or X-ray guidance but only in cases of significantly sized
      pericardial effusions. Whenever there is a limited sized but hemodynamically
      significant effusion, inferior pericardiotomy should be the preferred treatment
      strategy. In cases of cardiac tamponade following chest trauma a full median
      sternotomy can be a suitable approach for surgical treatment.

PMID- 21877219
TI  - [Primary and secondary prevention of erectile dysfunction].
AB  - Erectile dysfunction has an incidence of up to 75% in men aged 80, thus making
      primary prevention really important. Aetiologically multiple reasons are
      responsible for erectile dysfunction; therefore, recommendations for primary
      prevention contain different parts. The first one is to maintain a healthy
      arterial system and prevent atherosclerosis. Besides that diabetes, neurogenic
      disturbances or mental distress should be avoided. Physical activity, balanced
      nutrition, nonsmoking, unsaturated fatty acids and moderate alcohol consumption
      are preventive. Regular erections cause oxygenation of the cavernous body and
      prevent fibrosis which could lead to an insufficient occlusion of the cavernous
      veins. If the patient already suffers from coronary heart disease or diabetes,
      blood pressure, pulse, blood lipids and blood sugar should be as normal as
      possible. Erectile dysfunction might be the primary symptom of coronary heart
      disease; therefore, consideration should be given to a cardiac examination in the
      diagnostic setting.

PMID- 21877220
TI  - A regional blood flow model for beta2-microglobulin kinetics and for simulating
      intra-dialytic exercise effect.
AB  - A kinetic model based on first principles, for beta(2)-microglobulin, is
      presented to obtain precise parameter estimates for individual patient. To reduce
      the model complexity, the number of model parameters was reduced using a priori
      identifiability analysis. The model validity was confirmed with the clinical data
      of ten renal patients on post-dilution hemodiafiltration. The model fit resulted
      in toxin distribution volume (V(d)) of 14.22 +/- 0.75 L, plasma fraction in
      extracellular compartment (f(P)) of 0.39 +/- 0.03, and inter-compartmental
      clearance of 44 +/- 4.1 mL min(-1). Parameter estimates suggest that V(d) and
      f(P) are much higher in hemodialysis patients than in normal subjects. The
      developed model predicts larger removed toxin mass than that predicted by the two
      pool model. On the application front, the developed model was employed to explain
      the effect of intra-dialytic exercise on toxin removal. The presented simulations
      suggest that intra-dialytic exercise not only increases the blood flow to low
      flow region, but also decreases the inter-compartmental resistance. Combined,
      they lead to increased toxin removal during dialysis and reduced post-dialysis
      rebound. The developed model can assist in suggesting the improved dialysis dose
      based on beta(2)-microglobulin, and also lead to quantitative inclusion of intra
      dialytic exercise in the future.

PMID- 21877221
TI  - [The critical incident reporting system as an instrument of risk management for
      better patient safety].
AB  - The probability that an inpatient will be harmed by a medical procedure is at
      least 3% of all patients. As a consequence, hospital risk management has become a
      central management task in the health care sector. The critical incident
      reporting system (CIRS) as a voluntary instrument for reporting (near) incidents
      plays a key role in the implementation of a risk management system. The goal of
      the CIRS is to register system errors without assigning guilt or meting out
      punishment and at the same time increasing the number of voluntary reports.

PMID- 21877222
TI  - An X-ray micro-fluorescence study to investigate the distribution of Al, Si, P
      and Ca ions in the surrounding soft tissue after implantation of a calcium
      phosphate-mullite ceramic composite in a rabbit animal model.
AB  - Synthetic calcium phosphates, despite their bioactivity, are brittle. Calcium
      phosphate- mullite composites have been suggested as potential dental and bone
      replacement materials which exhibit increased toughness. Aluminium, present in
      mullite, has however been linked to bone demineralisation and neurotoxicity: it
      is therefore important to characterise the materials fully in order to understand
      their in vivo behaviour. The present work reports the compositional mapping of
      the interfacial region of a calcium phosphate--20 wt% mullite biocomposite/soft
      tissue interface, obtained from the samples implanted into the long bones of
      healthy rabbits according to standard protocols (ISO-10993) for up to 12 weeks. X
      ray micro-fluorescence was used to map simultaneously the distribution of Al, P,
      Si and Ca across the ceramic-soft tissue interface. A well defined and sharp
      interface region was present between the ceramic and the surrounding soft tissue
      for each time period examined. The concentration of Al in the surrounding tissue
      was found to fall by two orders of magnitude, to the background level, within ~35
      MUm of the implanted ceramic.

PMID- 21877223
TI  - Evidence of bioactivation of halomethanes and its relation to oxidative stress
      response in Chirostoma riojai, an endangered fish from a polluted lake in Mexico.
AB  - Halomethanes (HMs) are produced autochthonously in water bodies through the
      action of ultraviolet light in the presence of HM precursors, such as dissolved
      organic carbon and halogens. In mammals, toxic effects induced by HMs are diverse
      and include oxidative stress, which is also induced by divalent and polyvalent
      metals; however, in fish little information is available on HM metabolism and its
      possible consequences at the population level. In the present study, high CYP 2E1
      and GST theta-like activities were found in viscera of the Toluca silverside
      Chirostoma riojai from Lake Zumpango (LZ; central Mexico). Formaldehyde, one of
      the HM metabolites, was correlated with CYP 2E1 activity and also induced lipid
      peroxidation in viscera. Hepatic CYP 2E1 activity was correlated with GST theta
      like activity, suggesting the coupling of both pathways of HM bioactivation and
      its consequent oxidative damage. Sediment metals, among others, were also
      responsible for oxidative stress, particularly iron, lead, arsenic and manganese.
      However, under normal environmental conditions, the antioxidant enzymes of this
      species sustain catalysis adapted to oxidative stress. Findings suggest that this
      fish species apparently has mechanisms of adaptation and recovery that enable it
      to confront toxic agents of natural origin, such as metals and other substances
      formed through natural processes, e.g., HMs. This has allowed C. riojai to
      colonize LZ despite the high sensitivity of this species to xenobiotics of
      anthropogenic origin.

PMID- 21877224
TI  - Acute toxicity of nitrate and nitrite to sensitive freshwater insects, mollusks,
      and a crustacean.
AB  - Both point- and nonpoint-sources of pollution have contributed to increased
      inorganic nitrogen concentrations in freshwater ecosystems. Although numerous
      studies have investigated the toxic effects of ammonia on freshwater species,
      relatively little work has been performed to characterize the acute toxicity of
      the other two common inorganic nitrogen species: nitrate and nitrite. In
      particular, to our knowledge, no published data exist on the toxicity of nitrate
      and nitrite to North American freshwater bivalves (Mollusca) or stoneflies
      (Insecta, Plecoptera). We conducted acute (96-h) nitrate and nitrite toxicity
      tests with two stonefly species (Allocapnia vivipara and Amphinemura delosa), an
      amphipod (Hyalella azteca), two freshwater unionid mussels (Lampsilis siliquoidea
      and Megalonaias nervosa), a fingernail clam (Sphaerium simile), and a pond snail
      (Lymnaea stagnalis). Overall, we did not observe a particularly wide degree of
      variation in sensitivity to nitrate, with median lethal concentrations ranging
      from 357 to 937 mg NO(3)-N/l; furthermore, no particular taxonomic group appeared
      to be more sensitive to nitrate than any other. In our nitrite tests, the two
      stoneflies tested were by far the most sensitive, and the three mollusks tested
      were the least sensitive. In contrast to what was observed in the nitrate tests,
      variation among species in sensitivity to nitrite spanned two orders of
      magnitude. Examination of the updated nitrite database, including previously
      published data, clearly showed that insects tended to be more sensitive than
      crustaceans, which were in turn more sensitive than mollusks. Although the toxic
      mechanism of nitrite is generally thought to be the conversion of oxygen-carrying
      pigments into forms that cannot carry oxygen, our observed trend in sensitivity
      of broad taxonomic groups, along with information on respiratory pigments in
      those groups, suggests that some other yet unknown mechanism may be even more
      important.

PMID- 21877225
TI  - New genome size estimates of 134 species of arthropods.
AB  - Insect genome size diversity remains poorly sampled, with sparse and sporadic
      sampling of a few select orders and with many orders unrepresented or
      underrepresented in the genome size database. Here, we present 134 genome size
      estimates for 18 orders, including the first ever genome size estimates for eight
      orders, 38 families, 102 genera, and 131 species. Also reported here are three
      insect species genome size estimates that are corrections for unpublished genome
      size values that made it into the literature, including the smallest arthropod
      genome of the two spot spider mite (1C = 91 Mb). These estimates range from 91 to
      7,752 Mb and provide a broader picture of genome size variation within Insecta
      and among all Arthropods. Proposed developmental constraints for holometabolous
      insect genome sizes are supported, with the majority of the species examined
      falling well under the hypothesized 1,978 Mb (2 pg) limit. The only exceptions
      occur in the highly diverse beetles (Coleoptera) (154 < 1C < 2,578) and the
      Mecoptera (1,890 < 1C < 2,134). Hemimetabolous orders include species with larger
      genomes. Of these, the Orthopteran genomes remain the largest (675 < 1C < 7,752).
      Hemipteran genomes are smaller (407 < 1C < 1,230), but with a very notable
      exception, the Cicadidae family, with bloated genomes (5,238 < 1C < 7,000 Mb) of
      a size previously known to exist only within Orthoptera. The genome sizes in all
      other Hemimetabolous orders (521 Mb < 1C < 3,860 Mb) fall within the range
      exhibited by the Hemiptera. New preparations and procedures for insect genome
      estimates with frozen material are described and discussed. To further improve
      and extend the number and quality of arthropod genome size estimates, a new flow
      cytometry insect standard, Blattaria: Periplaneta americana? (1C = 3,338 Mb) is
      established for genome size determination of insect genomes in excess of 2,000
      Mb.

PMID- 21877226
TI  - Retrospective qualitative analysis of ecological networks under environmental
      perturbation: a copper-polluted intertidal community as a case study.
AB  - The coast of Chanaral Bay in northern Chile has been affected by copper mine
      wastes for decades. This sustained perturbation has disrupted the intertidal
      community in several ways, but the mechanisms behind the observed shifts in local
      biodiversity remain poorly understood. Our main goal was to identify the species
      (lumped into trophic groups) belonging to the Chanaral intertidal community that,
      being directly affected by copper pollution, contributed primarily to the
      generation of the observed changes in community structure. These groups of
      species were called initiators. We applied a qualitative modelling approach based
      only on the sign and direction of effects among species, and present a formula
      for predicting changes in equilibrium abundances considering stress on multiple
      variables simultaneously. We then applied this technique retrospectively to
      identify the most likely set of initiators. Our analyses allowed identification
      of a unique set of four initiators in the studied intertidal system (a group of
      algae, sessile invertebrates, a group of herbivores and starfish), which were
      hypothesized to be the primary drivers of the observed changes in community
      structure. In addition, a hypothesis was derived about how the perturbation
      affected these initiators. The hypothesis is that pollution affected negatively
      the population growth rate of both algae and sessile invertebrates and suppressed
      the interaction between herbivores and starfish. Our analytic approach, focused
      on identifying initiators, constitutes an advance towards understanding the
      mechanisms underlying human-driven ecosystem disruption and permits identifying
      species that may serve as a focal point for community management and restoration.

PMID- 21877227
TI  - Sharp decrease of genetic variation in two Spanish localities of razor clam Ensis
      siliqua: natural fluctuation or Prestige oil spill effects?
AB  - Pollution is one of the main concerns in marine ecosystems nowadays.
      Environmental anthropogenic-mediated toxicants may affect genetic diversity both
      at the individual and ecosystem levels and may also alter the genetic structure
      of populations. This study examined the temporal pattern of genetic diversity
      among populations of the benthic bivalve Ensis siliqua in two locations of
      Galicia, following the Prestige oil spillage. On November 13, 2002 the oil tanker
      Prestige sank at 240 km from Galician coast and 63,000 tonnes of heavy fuel were
      released to the marine environment. E. siliqua samples were sampled between 2001
      and 2006. Genetic variation was assessed by means of Random Amplification of
      Polymorphic DNA (RAPD). A significant decrease in genetic diversity was observed
      for the 2006 samples. Nei's genetic distance, fixation index (PhiPT), and PCA
      values also supported differences in the 2006 samples. We hypothesize that the
      temporal genetic variation observed in E. siliqua populations is due to a strong
      effect of genetic drift caused by a reduction in population size and that the
      indirect effects of the Prestige spill possibly caused this reduction.

PMID- 21877228
TI  - Differences in ecological impacts of systemic insecticides with different
      physicochemical properties on biocenosis of experimental paddy fields.
AB  - The environmental risks of pesticides are typically determined by laboratory
      single-species tests based on OECD test guidelines, even if biodiversity should
      also be taken into consideration. To evaluate how realistic these assessments
      are, ecological changes caused by the systemic insecticides imidacloprid and
      fipronil, which have different physicochemical properties, when applied at
      recommended commercial rates on rice fields were monitored using experimental
      paddy mesocosms. A total of 178 species were observed. There were no significant
      differences in abundance of crop arthropods among the experimental paddies.
      However, zooplankton, benthic and neuston communities in imidacloprid-treated
      field had significantly less abundance of species than control and fipronil
      fields. Significant differences in abundance of nekton community were also found
      between both insecticide-treated paddies and control. Influences on the growth of
      medaka fish were also found in both adults and their fries. Both Principal
      Response Curve analysis (PRC) and Detrended Correspondence Analysis (DCA) showed
      the time series variations in community structure among treatments, in particular
      for imidacloprid during the middle stage of the experimental period. These
      results show the ecological effect-concentrations (LOEC ~ 1 MUg/l) of these
      insecticides in mesocosms, especially imidacloprid, are clearly different from
      their laboratory tests. We suggest that differences in the duration of the
      recovery process among groups of species are due to different physicochemical
      properties of the insecticides. Therefore, realistic prediction and assessment of
      pesticide effects at the community level should consider not only the sensitivity
      traits and interaction among species but also the differences in physicochemical
      characteristics of each pesticide.

PMID- 21877229
TI  - Improving mesocosm data analysis through individual-based modelling of control
      population dynamics: a case study with mosquitofish (Gambusia holbrooki).
AB  - Experimental ecosystems such as mesocosms have been developed to improve the
      ecological relevance of ecotoxicity test. However, in mesocosm studies, the
      number of replicates is limited by practical and financial constraints. In
      addition, high levels of biological organization are characterized by a high
      variability of descriptive variables. This variability and the poor number of
      replicates have been recognized as a major drawback for detecting significant
      effects of chemicals in mesocosm studies. In this context, a tool able to predict
      precisely control mesocosms outputs, to which endpoints in mesocosms exposed to
      chemicals could be compared should constitute a substantial improvement. We
      evaluated here a solution which consists in stochastic modelling of the control
      fish populations to assess the probabilistic distributions of population
      endpoints. An individual-based approach was selected, because it generates
      realistic fish length distributions and accounts for both individual and
      environmental sources of variability. This strategy was applied to mosquitofish
      (Gambusia holbrooki) populations monitored in lentic mesocosms. We chose the
      number of founders as a so-called "stressor" because subsequent consequences at
      the population level could be expected. Using this strategy, we were able to
      detect more significant and biologically relevant perturbations than using
      classical methods. We conclude that designing an individual-based model is very
      promising for improving mesocosm data analysis. This methodology is currently
      being applied to ecotoxicological issues.

PMID- 21877230
TI  - Interactions of silver nanoparticles with the marine macroalga, Ulva lactuca.
AB  - The marine macroalga, Ulva lactuca, has been exposed for 48 h to different
      concentrations of Ag added as either silver nanoparticles (AgNP) or aqueous metal
      (AgNO(3)) and the resulting toxicity, estimated from reductions in quenching of
      chlorophyll-a fluorescence, and accumulation of Ag measured. Aqueous Ag was toxic
      at available concentrations as low as about 2.5 MUg l(-1) and exhibited
      considerable accumulation that could be defined by the Langmuir equation. AgNP
      were not phytotoxic to the macroalga at available Ag concentrations up to at
      least 15 MUg l(-1) and metal measured in U. lactuca was attributed to a physical
      association of nanoparticles at the algal surface. At higher AgNP concentrations,
      a dose-response relationship was observed that was similar to that for aqueous Ag
      recorded at much lower concentrations. These findings suggest that AgNP are only
      indirectly toxic to marine algae through the dissolution of Ag(+) ions into bulk
      sea water, albeit at concentrations orders of magnitude greater than those
      predicted in the environment.

PMID- 21877231
TI  - Heritability across the distribution: an application of quantile regression.
AB  - We introduce a new method for analyzing twin data called quantile regression.
      Through the application presented here, quantile regression is able to assess the
      genetic and environmental etiology of any skill or ability, at multiple points in
      the distribution of that skill or ability. This method is compared to the Cherny
      et al. (Behav Genet 22:153-162, 1992) method in an application to four different
      reading-related outcomes in 304 pairs of first-grade same sex twins enrolled in
      the Western Reserve Reading Project. Findings across the two methods were
      similar; both indicated some variation across the distribution of the genetic and
      shared environmental influences on non-word reading. However, quantile regression
      provides more details about the location and size of the measured effect.
      Applications of the technique are discussed.

PMID- 21877232
TI  - Palate hyperpigmentation caused by prolonged use of the anti-malarial
      chloroquine.
AB  - The side-effects of many drugs manifest in the oral mucosa. The anti-malarial
      agent chloroquine diphosphate, which is also used to treat immunological,
      dermatological, and rheumatological disorders, usually causes pigmentary changes
      in the oral mucosa. This report presents a case of palate pigmentation related to
      the prolonged use of chloroquine diphosphate caused by the deposition of drug
      metabolites in the mucosa. Healthcare professionals must be aware of these drugs
      and their adverse effects in order to make the correct diagnosis, decide on the
      optimal treatment for the condition, or refer the patient to an appropriate
      specialist.

PMID- 21877233
TI  - Dairy intake, blood pressure and incident hypertension in a general British
      population: the 1946 birth cohort.
AB  - PURPOSE: We aimed to examine the association between intake of different
      subgroups of dairy products and blood pressure and incident hypertension 10 years
      later, adjusting for confounding factors. METHODS: We studied 1,750 British men
      and women from the 1946 British birth cohort from 1989 to 1999 (age 43 and 53
      years, respectively). Diet was assessed by 5-day food diaries using photographs
      in the estimation of portion size. Systolic (sbp) and diastolic (dbp) blood
      pressure and prevalent hypertension were assessed at age 43 and 53 years. Linear
      regression and logistic regression were used to examine 10-year blood pressure
      levels and incident hypertension by baseline dairy intake. RESULTS: There was a
      weak non-significant trend of a protective effect of total dairy intake on blood
      pressure and incident hypertension, but no evidence for a dose-response
      relationship (OR for incident hypertension: 0.88 (95% CI 0.68;1.14) 2nd vs. 1st
      tertile and 0.93 (95% CI 0.72;1.18) 3rd vs. 1st tertile). Higher intake of low
      fat and fermented dairy was linked to a higher sbp but in a nonlinear manner.
      Adjustment for other dietary factors, health behaviours and BMI attenuated these
      associations. CONCLUSIONS: Total dairy intake and specific dairy subgroups were
      not associated with blood pressure and incident hypertension among a
      representative sample of British adults after adjustment for confounding factors.

PMID- 21877234
TI  - Health care disparities in the acute management of venous thromboembolism based
      on insurance status in the U.S.
AB  - Acute venous thromboembolism (VTE) is common, costly, and potentially lethal.
      Therapeutic anticoagulation requires timely, closely monitored medical follow-up.
      If ineffective, clinical outcomes worsen and resource utilization increases. This
      risk may be magnified in uninsured patients. This study examined VTE care in
      hospital patients and investigated differences based on insurance status. We
      performed a retrospective chart review on medical VTE patients at an academic
      teaching hospital between December 1, 2007 and April 30, 2009. We reviewed
      medical records for demographics, insurance, admission status, length of stay
      (LOS), and 30-day Emergency Department (ED) recidivism and hospital readmission.
      Measured outcomes were analyzed based on payer source. We identified 234 medical
      VTE patients; 67 patients were uninsured (28.6%). 106 patients (45.3%) presented
      with deep vein thrombosis only. Most VTE patients were admitted to the hospital
      (171; 73.1%), including all 128 pulmonary embolism patients. Admitted uninsured
      patients averaged a LOS of 5.5 versus 3.7 days for insured (P = 0.03), with ED
      recidivism rates of 26.1 versus 11.3%, respectively (P = 0.02). Average cost for
      all VTE care in uninsured patients was $12,297 versus $7,758 for insured patients
      (P = 0.04). This study identified disparities in medical care and resource
      utilization for medical VTE patients based on insurance. Uninsured VTE patients
      were hospitalized nearly two additional days and were more than two times as
      likely to return to the ED within 30 days compared to insured patients.
      Additional research is needed to explain these disparities, and to explore system
      improvements for the uninsured VTE patient.

PMID- 21877235
TI  - Two monitoring methods of oral anticoagulant therapy in patients with mechanical
      heart valve prothesis: a meta-analysis.
AB  - Oral anticoagulant therapy (OAT) with warfarin has become the standard therapy
      for the patients with mechanical heart valve prothesis. The monitoring method of
      self-monitoring or self-management was promising to optimize the use of warfarin,
      but most of previous studies have included patients with various indications of
      OAT, which made it difficult to extrapolate the results to the specific patient
      population with mechanical heart valve prostheses. This study was intended to
      evaluate the new and traditional monitoring methods in patients with mechanical
      heart valve prostheses. Relevant literature finished before Dec. 2010 were
      searched through a number of digital databases. And then they were pooled by
      RevMan 4.2 and R 2.13.0 in three fields: rate within the target range, test
      frequency and occurrence rate of poor events. Five randomized control trials with
      a total of 2,219 patients were identified. Pooled estimates showed reductions in
      thromboembolic events (OR 0.52, 95% CI 0.35-0.77; P = 0.0012) and all-cause
      mortality (OR 0.50, 95% CI 0.29-0.86; P = 0.0115). No difference was noted in
      major and minor haemorrhage. All trials reported improvements in the mean
      proportion of international normalized ratios in range. Self-monitoring and self
      management can improve the quality of OAT in the patients with mechanical heart
      valve prostheses. The patients spend more time within the therapeutic range
      resulting in decreases in thromboembolic events and mortality, with no increase
      in haemorrhage. However, self-monitoring and self-management was not feasible for
      all patients, and require identification and education of suitable candidates.
      The success of self-monitoring and self-management method depends on consistent,
      regular, and frequent testing.

PMID- 21877236
TI  - Adaptation of photosystem II to high and low light in wild-type and triazine
      resistant Canola plants: analysis by a fluorescence induction algorithm.
AB  - Plants of wild-type and triazine-resistant Canola (Brassica napus L.) were
      exposed to very high light intensities and after 1 day placed on a laboratory
      table at low light to recover, to study the kinetics of variable fluorescence
      after light, and after dark-adaptation. This cycle was repeated several times.
      The fast OJIP fluorescence rise curve was measured immediately after light
      exposure and after recovery during 1 day in laboratory room light. A fluorescence
      induction algorithm has been used for resolution and analysis of these curves.
      This algorithm includes photochemical and photo-electrochemical quenching release
      components and a photo-electrical dependent IP-component. The analysis revealed a
      substantial suppression of the photo-electrochemical component (even complete in
      the resistant biotype), a partial suppression of the photochemical component and
      a decrease in the fluorescence parameter F (o) after high light. These effects
      were recovered after 1 day in the indoor light.

PMID- 21877238
TI  - Residual pyrethroids in fresh horticultural products in Sonora, Mexico.
AB  - This study was conducted to evaluate the presence of cyhialothrin, cyfluthrin,
      cypermethrin, fenvalerate, and deltamethrin in vegetables produced and consumed
      in Sonora, Mexico. A total of 345 samples were collected from cluster sampling of
      markets and fields. Approximately 9% of the samples tested positive for
      pyrethroids (residue range 0.004-0.573 mg kg(-1)). Based on the results, the
      potential toxicological risk of human exposure to the pyrethroid insecticides
      measured in vegetables appears to be minimal, with the estimated exposure being
      1,000 times lower than admissible levels.

PMID- 21877237
TI  - Comparison of transdifferentiated and untransdifferentiated human umbilical
      mesenchymal stem cells in rats after traumatic brain injury.
AB  - Transdifferentiated and untransdifferentiated mesenchymal stem cells (MSCs) have
      shown therapeutic benefits in central nervous system (CNS) injury. However, it is
      unclear which would be more appropriate for transplantation. To address this
      question, we transplanted untransdifferentiated human umbilical mesenchymal stem
      cells (HUMSCs) and transdifferentiated HUMSCs (HUMSC-derived neurospheres, HUMSC
      NSs) into a rat model of traumatic brain injury. Cognitive function, cell
      survival and differentiation, brain tissue morphology and neurotrophin expression
      were compared between groups. Significant improvements in cognitive function and
      brain tissue morphology were seen in the HUMSCs group compared with HUMSC-NSs
      group, which was accompanied by increased neurotrophin expression. Moreover, only
      few grafted cells survived in both the HUMSCs and HUMSC-NSs groups, with very few
      of the cells differentiating into neural-like cells. These findings indicate that
      HUMSCs are more appropriate for transplantation and their therapeutic benefits
      may be associated with neuroprotection rather than cell replacement.

PMID- 21877239
TI  - Is there a difference between center and home care providers' training,
      perceptions, and practices related to obesity prevention?
AB  - To compare the obesity related training, practices, and perceptions of home child
      care providers and center care providers. A self-administered survey was
      collected from child care providers who attended local child care training
      workshops in east central Illinois from March 2009 to August 2010. Study results
      were based on responses from 88 home care providers and 94 center providers. The
      survey questions addressed child care providers' training in the prior year,
      their obesity prevention practices including written policies, their perceptions
      of influences on children's health, and factors determining food menu selection.
      Paired t tests and Chi-square tests were used to compare the difference by child
      care type. 81.9% of home care providers and 58.6% of center care providers
      received nutrition training, while 66.7 and 43.0% of these providers received
      physical activity training, respectively. Nutrition content, guidelines or state
      regulations, and food availability were the most important factors that
      influenced both types of care providers' food service menus. Both care provider
      types perceived they have less influence on children's food preferences, eating
      habits, and weight status compared to the home environment. However, home care
      providers perceived a smaller discrepancy between the influences of child care
      and home environments compared to center care providers. Compared to center
      providers, home care providers were more likely to have had training, be involved
      with health promotion activities, and rate their influence higher on children's
      health behaviors. Findings underscore the need for obesity prevention efforts in
      both types of child care settings.

PMID- 21877241
TI  - Giant abdomino-pelvic adipose tumors of childhood.
AB  - Adipose tumors are rare in pediatric age and are commonly represented by benign
      forms: lipoma and lipoblastoma/lipoblastomatosis. Generally localized in
      subcutaneous tissue of the trunk and extremities, they can exceptionally occur as
      giant intra-peritoneal or pelvic masses. These tumors could reach considerable
      size prior to diagnosis since they are asymptomatic. The authors report a case
      series of three giant abdomino-pelvic adipose tumors.

PMID- 21877240
TI  - Laparoscopic surgery for acute neonatal appendicitis.
AB  - We present the first two cases of acute neonatal appendicitis operated on through
      the laparoscopic approach. Acute neonatal appendicitis is uncommon and rarely
      considered by clinicians when assessing the neonatal acute abdomen. Our two cases
      demonstrate the potential value of diagnostic laparoscopy in the acute neonatal
      abdomen that poses a diagnostic dilemma. Furthermore, technical modifications of
      well-established laparoscopic techniques in the older child enable its use in
      neonates as a therapeutic tool.

PMID- 21877242
TI  - Minimally invasive partial or total nephrectomy in children: a comparison between
      transperitoneal and retroperitoneal approaches.
AB  - INTRODUCTION AND OBJECTIVES: We present data from a single surgeon experience of
      paediatric transperitoneal (TP) and retroperitoneal (RP) minimally invasive
      approaches for partial (PN) and total nephrectomy (TN). METHODS: A retrospective
      review was conducted in the patients undergoing nephrectomy between 2003 and
      2008. Patients were divided depending on PN or TN and the approach (RP or TP).
      Primary outcome was the need to convert to an open procedure. Secondary outcomes
      included operation time, length of stay (LOS) and complications. Statistical
      analysis included Fisher's exact test. RESULTS: 68 patients underwent minimally
      invasive TN/PN, 49 (72%) RP versus 19 (28%) TP. There were no differences between
      the groups in terms of sex, age, pathology, LOS, complication rate and conversion
      rate. Neither group recorded mortality. Conversion occurred because of difficult
      anatomy or the kidney size rather than an adverse event. Overall, there was no
      difference in operative time between the RP and TP. This was also the case for TN
      only. However, the PN subgroup demonstrated a decreased operative time with RP (p
      = 0.049) possibly due to better anatomical delineation. There were no
      complications. CONCLUSIONS: Minimally invasive TN or PN can be performed via
      retroperitoneal or transperitoneal routes with minimal morbidity. With training,
      PN via retroperitoneal approach can be achieved with significantly reduced
      operative time.

PMID- 21877243
TI  - Partial nephroureterectomy in a duplex system in children: the need for
      additional bladder procedures.
AB  - INTRODUCTION AND OBJECTIVES: Heminephroureterectomy (HN) is our treatment of
      choice in a duplex system with non-functioning moiety. We examined the need for
      endoscopic incision (EI)/bladder reconstructive surgery (BRS) and whether
      ureteroceles and/or vesicoureteric reflux (VUR) influenced management options.
      METHODS: Retrospective study of patients undergoing HN by a single surgeon (2003
      2008). Patients were classified according to the presence (Group 1) or absence
      (Group 2) of ureterocele. The groups were subdivided with coexisting dilating VUR
      (a) or not (b). Statistical analysis included Fisher's exact test. RESULTS:
      Thirty-one children were identified. Seventeen (54.8%) had ureterocele (Group 1)
      and 14 patients had no ureterocele (Group 2). Group 1 had eight with VUR (1a) and
      nine without (1b). Group 2 had seven with VUR (2a) and seven without (2b).
      Significantly more patients with ureterocele required EI/BRS (p = 0.006). Five
      (29%) in Group 1 required BRS versus none in Group 2 (p = 0.04). Six (75%) in
      Group 1a underwent EI/BRS versus three (33%) in Group 1b (p = 0.15).
      Significantly more in Group 1a required EI prior to HN versus Group 1b (p =
      0.04). Similar numbers of patients required BRS in Groups 1a and 1b (p = 0.61).
      CONCLUSIONS: In the absence of ureterocele, there is minimal likelihood of
      requiring surgery apart from HN, independent of VUR. Presence of ureterocele is
      an indicator for additional procedure within the bladder. There is a higher
      incidence of EI when ureterocele co-exists with dilating VUR.

PMID- 21877244
TI  - Down-regulation of adiponectin in patients with familial Mediterranean fever
      during attack-free period.
AB  - To evaluate the circulating levels of adipokines (leptin and adiponectin) and
      ghrelin in patients with familial Mediterranean fever (FMF) and also to assess
      the relationships between these molecules and disease-related parameters. Forty
      eight FMF patients in attack-free period (31 men, [M], 17 women, [F], mean age
      35.8 +/- 8.6 years, and a mean body mass index [BMI] of 24.7 +/- 3.1) and 40 age
      , sex-, and BMI-matched healthy controls (24 M, 16 F, mean age 35.5 +/- 8.5
      years, and a mean BMI of 24.5 +/- 2.8) were included in the study. Patients and
      controls with a history of any other chronic diseases and obese or underweight
      subjects were excluded. High-sensitive C-reactive protein (hs-CRP), leptin,
      adiponectin, and total ghrelin concentrations were studied. Age, sex, BMI, waist
      circumference, and smoking status were similar between FMF patients and controls
      (P > 0.05). Adipose tissue-derived molecules including leptin, and adiponectin
      were lower than healthy controls but only adiponectin levels reached the
      statistically significance (16.7 +/- 8.9 ng/ml vs. 27.7 +/- 15.9 ng/ml, P <
      0.001) and leptin concentrations just missed significance (25.2 +/- 16.2 ng/ml
      vs. 34.9 +/- 27.2 ng/ml, P = 0.051). Ghrelin concentrations were not different
      between the groups. Adiponectin levels were significantly and negatively
      correlated with hs-CRP (P < 0.05, r = -0.24). The results of this study suggest
      that low-grade chronic inflammation during attack-free period in FMF patients may
      suppress adiponectin production or low levels of adiponectin might contribute to
      subclinical inflammation in these patients.

PMID- 21877245
TI  - Adult-onset Still's disease: how to make a diagnosis in an atypical case.
AB  - Adult-onset Still's disease (AOSD) is a complicated multi-systemic inflammatory
      disease, the main features of which are high spiking fever, evanescent rash,
      polyarthralgia, lymphadenopathy, hepatosplenomegaly and leukocytosis. The
      pathogenesis and etiology of AOSD are still unknown. We report a case of atypical
      AOSD presenting with only arthralgia, fever, lymphadenopathy, slightly elevated
      serum C-reactive protein and ferritin levels and a slightly elevated erythrocyte
      sedimentation rate; these signs and symptoms did not fulfill the proposed
      diagnostic criteria of both Cush and Yamaguchi. After exclusion of other likely
      diagnoses, a diagnosis of atypical AOSD was made, and a low dose of
      corticosteroids was effective in resolving all of the patient's symptoms. More
      clinical practice and research are needed to determine pathogenesis and etiology
      of AOSD and to amend the diagnostic criteria to include such atypical cases.

PMID- 21877246
TI  - Anteroposterior and varus-valgus laxity of the knee increase after stair climbing
      in patients with mild osteoarthritis.
AB  - The aim of this study was to measure exercise-induced changes in knee joint
      laxity in patients with knee osteoarthritis (OA). The study subjects were 46
      female patients with OA and 22 age- and sex-matched normal controls. Radiographs
      of the knee were taken in all subjects, and the disease severity was graded
      according to the Kellgren and Lawrence (K-L) grading system. The K-L grade of the
      control subjects (non-OA group) was 0-1. The OA patients were divided into those
      with mild OA (K-L grade 2, n = 20) and advanced OA (K-L grade 3-4, n = 26). The
      subject climbed up and down 8 steps on a staircase apparatus over a period of 10
      min. The anteroposterior (A-P) translation was measured with KT2000 arthrometer,
      and varus-valgus (V-V) rotation was measured on stress radiographs before and
      after the stair climbing. The Deltachange in A-P translation after the exercise
      was significantly larger in mild OA group than other groups (P < 0.005). The
      Deltachange in V-V rotation after exercise was significantly larger in mild and
      advanced OA groups than the control (P < 0.003). There were no significant
      differences in A-P laxity and V-V laxity before exercise among the non-OA, mild
      OA and advanced OA groups. Exercise resulted in significant changes in A-P knee
      joint laxity in patients with mild OA relative to the control. The results
      suggest that daily physical activities (e.g., knee bending or squatting) play a
      role in the development of knee laxity, particularly in patients with mild OA,
      and that progression of knee OA seems to correlate with increments of A-P knee
      joint laxity.

PMID- 21877248
TI  - SCF and TLR4 ligand cooperate to augment the tumor-promoting potential of mast
      cells.
AB  - Mast cells may have either antitumor or tumor-promoting potential. Nevertheless,
      mast cells in tumor microenvironment have been found to promote tumor growth. So
      far the mechanisms underlying the modulation of mast cell function in tumor
      microenvironment remains to be fully elucidated. Here, we report that tumor
      promoting potential of mast cells could be augmented by molecules released from
      damaged tumor cells through cooperative stimulation of stem cell factor (SCF) and
      ligand for Toll-like receptor 4 (TLR4). Co-simulation with SCF and TLR4 ligand
      inhibited mast cell degranulation, but efficiently induced the production and
      secretion of VEGF, PDGF, and IL-10. Although TLR4 ligand alone may induce IL-12
      expression in mast cells, co-stimulation with SCF and TLR4 ligand induced the
      expression of IL-10, but not IL-12, in mast cells. The phosphorylation of
      GSK3beta was crucial for the effect of SCF and TLR4 ligand. In addition to
      inducing phosphorylation of GSK3beta at Ser9 through PI3K pathway, SCF and TLR4
      ligand cooperated to induce phosphorylation of GSK3beta at Tyr216 by simultaneous
      activation of ERK and p38MAPK pathways. Both phospho-Ser9 and phospho-Tyr216 of
      GSK3beta were required for IL-10 expression induced by SCF/TLR4 ligand, whereas
      suppressive effect of SCF/TLR4 ligand on mast cell degranulation was related to
      phospho-Tyr216. Importantly, the effect of SCF and TLR4 ligand on mast cells
      could be abrogated by inhibiting phosphorylation of GSK3beta at Tyr216. These
      findings disclose the mechanisms underlying the modulation of mast cell function
      in tumor microenvironment, and suggest that inhibiting GSK3beta in mast cells
      will be beneficial to the treatment of cancer.

PMID- 21877247
TI  - Expression of anti-HVEM single-chain antibody on tumor cells induces tumor
      specific immunity with long-term memory.
AB  - Genetic engineering of tumor cells to express immune-stimulatory molecules,
      including cytokines and co-stimulatory ligands, is a promising approach to
      generate highly efficient cancer vaccines. The co-signaling molecule, LIGHT, is
      particularly well suited for use in vaccine development as it delivers a potent
      co-stimulatory signal through the Herpes virus entry mediator (HVEM) receptor on
      T cells and facilitates tumor-specific T cell immunity. However, because LIGHT
      binds two additional receptors, lymphotoxin beta receptor and Decoy receptor 3,
      there are significant concerns that tumor-associated LIGHT results in both
      unexpected adverse events and interference with the ability of the vaccine to
      enhance antitumor immunity. In order to overcome these problems, we generated
      tumor cells expressing the single-chain variable fragment (scFv) of anti-HVEM
      agonistic mAb on the cell surface. Tumor cells expressing anti-HVEM scFv induce a
      potent proliferation and cytokine production of co-cultured T cells. Inoculation
      of anti-HVEM scFv-expressing tumor results in a spontaneous tumor regression in
      CD4+ and CD8+ T cell-dependent fashion, associated with the induction of tumor
      specific long-term memory. Stimulation of HVEM and 4-1BB co-stimulatory signals
      by anti-HVEM scFv-expressing tumor vaccine combined with anti-4-1BB mAb shows
      synergistic effects which achieve regression of pre-established tumor and T cell
      memory specific to parental tumor. Taken in concert, our data suggest that
      genetic engineering of tumor cells to selectively potentiate the HVEM signaling
      pathway is a promising antitumor vaccine therapy.

PMID- 21877249
TI  - On identifying plausibility and deliberative public policy : commentary on:
      "Negotiating plausibility: intervening in the future of nanotechnology".
AB  - The identification of plausible epistemic approaches in science as well as the
      social problem definitions with which scientists implicitly work is essential for
      the quality of a deliberative public policy. While responding to the Nanofutures
      project, I will reflect on the essential elements of such a policy.

PMID- 21877250
TI  - Respiratory epithelial adenomatoid hamartomas of the olfactory clefts.
AB  - The objective of this study is to report a 5-year experience with Respiratory
      Epithelial Adenomatoid Hamartoma (REAH) of the olfactory clefts. The study design
      is retrospective observational study and the setting is in a Tertiary medical
      center. The charts of all adult patients operated on bilateral nasal polyps
      between 2003 and 2008 were retrospectively checked up on the diagnosis of REAH.
      Three periods have been distinguished according to our experience with REAH. REAH
      can be observed either as bilateral pseudotumours confined to the olfactory
      clefts (n = 12 between 2003 and 2008) or associated to nasal polyposis of the
      ethmoid labyrinths. As the diagnosis of associated REAH became more evident, the
      number of recognized cases increased from 0% in 2003 and 2004 to 1.6% in 2005
      (1/64 patients) and 12.5% in 2006 (10/80 patients) (period 1). Systematic
      endoscopy of the olfactory clefts during ethmoid labyrinth surgery increased the
      proportion to 27% (27/100 patients) (period 2). Systematic biopsies of abnormal
      mucosa in the olfactory clefts during ethmoid surgery increased the proportion to
      48% (31/65 patients). The histopathological diagnosis of REAH has been described
      in 1995 and added to the World Health Organization classification of tumours in
      2005. Pseudotumoural REAH confined to the olfactory clefts represent a
      differential diagnosis for bilateral naso-ethmoidal polyposis. The significance
      of REAH associated to naso-ethmoidal polyposis is unclear.

PMID- 21877251
TI  - RNA released from necrotic keratinocytes upregulates intercellular adhesion
      molecule-1 expression in melanocytes.
AB  - Intercellular adhesion molecule-1 (ICAM-1) expression has been detected in
      melanocytes around active vitiligo patches as well as in surgically transplanted
      melanocytes. However, it is unclear whether and how skin injury induces the
      inappropriate expression of ICAM-1 and other proinflammatory genes in
      melanocytes. We previously reported that human melanocytes expressed TLR3. We
      hypothesized that the TLR3 expressed in melanocytes may recognize skin injury by
      binding to the endogenous ligands secreted by the damaged keratinocytes. Here we
      showed that RNA released from necrotic keratinocytes induced the upregulation of
      ICAM-1 protein and mRNA, as shown by FACS and real-time RT-PCR. Use of NF-kappaB
      inhibitor prevents upregulation of ICAM-1 in melanocytes indicating a direct role
      of NF-kappaB in necrotic keratinocyte-mediated upregulation of ICAM-1. Using a
      shRNA-expressing lentivirus, we demonstrated that in human melanocytes, TLR3
      seems to be necessary for the upregulation of ICAM-1. Using oligonucleotide
      microarray, we demonstrated a dramatic increase in proinflammatory cytokine and
      chemokine transcripts (CXCL10, CXCL11, TNFSF10, CCL5, CCL4, CCL2, IFNB1, CCL20,
      IL-8, and CCL11). These observations suggested that RNA released from necrotic
      keratinocytes might act as an endogenous TLR3 ligand for the stimulation of ICAM
      1 and other proinflammatory gene expression in human melanocytes, which might be
      involved in the pathogenesis of vitiligo following skin physical trauma.

PMID- 21877252
TI  - Liver transplantation trends in the HIV population.
AB  - There is a paucity of information on the utilization patterns of liver
      transplantation (LT) for HIV-positive individuals. The aim of this study is to
      examine the trends in LT of HIV patients in the US. This study was a
      retrospective analysis using the UNOS database (1999-2008). There were 135 HIV
      positive patients. There was a steady increase in the number of LT recipients
      over time as well as regional variation. Ethnic minorities accounted for 33.3%
      and there was no ethnic difference in survival. Though LT for HIV-positive
      patients is on the rise, significant variations exist in patient demographics,
      geographic location, and insurance payer.

PMID- 21877253
TI  - Generation and functional analysis of monoclonal antibodies against the second
      extracellular loop of human M3 muscarinic acetylcholine receptor.
AB  - The M3 muscarinic acetylcholine receptor (M3R) plays a crucial role in the
      activation of salivary and lachrymal glands. The M3R contains four extracellular
      domains (the N-terminal, and the first, second, and third extracellular loops),
      and we recently detected antibodies against each of these four domains in a
      subgroup of patients with Sjogren's syndrome (SS). Functional analysis indicated
      that the influence of such anti-M3R antibodies on salivary secretion might differ
      based on the epitopes to which they bind. To clarify the relationship between B
      cell epitopes on the M3R and its function, we generated two hybridomas producing
      anti-M3R monoclonal antibodies against the second extracellular loop of M3R (anti
      M3R(2nd) mAbs) and analyzed their function by Ca(2+)-influx assays, using a human
      salivary gland (HSG) cell line. These two anti-M3R(2nd) mAbs suppressed Ca(2+)
      influx in the HSG cells induced by cevimeline stimulation, suggesting that
      autoantibodies against the second extracellular loop of M3R could be involved in
      salivary dysfunction in patients with SS.

PMID- 21877254
TI  - Experiencing violence as a predictor of drug use relapse among former drug users
      in Baltimore, Maryland.
AB  - The purpose of this study was to examine experiencing violence as a predictor of
      subsequent drug relapse among a sample of former crack, cocaine, and heroin users
      in Baltimore, MD, USA. The sample consists of 228 former drug users in Baltimore
      who were recruited through street outreach. Mixed-effects models were used to
      examine experiencing violence as a predictor of drug relapse at follow-up after
      adjusting for clustering of responses among participants living in the same
      census block. Using longitudinal data, we found that experiencing violence in the
      past year predicted drug relapse at 2-year follow-up among former drug users.
      Results indicate experiencing violence is a determinant of drug use relapse and
      highlight the importance of addressing the fundamental issues of violence
      experienced in inner-city communities. Addressing the extent of recent violence
      among drug treatment participants, providing coping skills, and reducing
      community violence are strategies that may address the link between violence and
      drug relapse.

PMID- 21877255
TI  - Addressing the social and environmental determinants of urban health equity:
      evidence for action and a research agenda.
AB  - Urban living is the new reality for the majority of the world's population. Urban
      change is taking place in a context of other global challenges--economic
      globalization, climate change, financial crises, energy and food insecurity, old
      and emerging armed conflicts, as well as the changing patterns of communicable
      and noncommunicable diseases. These health and social problems, in countries with
      different levels of infrastructure and health system preparedness, pose
      significant development challenges in the 21st century. In all countries, rich
      and poor, the move to urban living has been both good and bad for population
      health, and has contributed to the unequal distribution of health both within
      countries (the urban-rural divide) and within cities (the rich-poor divide). In
      this series of papers, we demonstrate that urban planning and design and urban
      social conditions can be good or bad for human health and health equity depending
      on how they are set up. We argue that climate change mitigation and adaptation
      need to go hand-in-hand with efforts to achieve health equity through action in
      the social determinants. And we highlight how different forms of governance can
      shape agendas, policies, and programs in ways that are inclusive and health
      promoting or perpetuate social exclusion, inequitable distribution of resources,
      and the inequities in health associated with that. While today we can describe
      many of the features of a healthy and sustainable city, and the governance and
      planning processes needed to achieve these ends, there is still much to learn,
      especially with respect to tailoring these concepts and applying them in the
      cities of lower- and middle-income countries. By outlining an integrated research
      agenda, we aim to assist researchers, policy makers, service providers, and
      funding bodies/donors to better support, coordinate, and undertake research that
      is organized around a conceptual framework that positions health, equity, and
      sustainability as central policy goals for urban management.

PMID- 21877257
TI  - A clinical commentary on the article "patient-to-patient variability in
      autologous pericardial matrix scaffolds for cardiac repair".

PMID- 21877256
TI  - Cardiac responses to the intrapericardial delivery of metoprolol: targeted
      delivery compared to intravenous administration.
AB  - Anti-arrhythmic drugs have narrow therapeutic ranges and typically can engender
      harmful side effects. The intrapericardial (IP) delivery of anti-arrhythmic
      agents proposes to achieve higher myocardial levels while minimizing plasma
      concentrations, thus diminishing systemic side effects. Furthermore, IP delivery
      enables concentrations at the target site to be more precisely controlled. Our
      study objective was to compare the relative cardiac effects of intrapericardial
      administration of metoprolol to standard intravenous (IV) delivery in a swine
      surgical model. In order to answer the question of how IP metoprolol affects
      sinus tachycardia, atrial electrophysiology, and pharmacokinetics compared with
      IV delivery, a medial sternotomy was performed on 21 swine that were divided into
      three groups: (1) After inducing sinus tachycardia, metoprolol boluses were
      delivered IP (n = 4) or IV (n = 4); (2) metoprolol was administered either IP (n
      = 3) or IV (n = 3) with saline controls (n = 3), and electrophysiologic data were
      collected; (3) metoprolol levels were tracked both in the blood (IV, n = 2) and
      pericardial (IP, n = 2) fluid. After either IP or IV delivery of metoprolol,
      heart rates were lowered significantly to 70% and 73% of control rate,
      respectively. The therapeutic effect of IV-administered metoprolol was
      considerably reduced after 1 h but was sustained longer in the IP group.
      Additionally, ventricular contractility and mean arterial pressure parameters
      were significantly lower in IV-treated animals but were nearly unaffected in IP
      treated animals. With IP administration, the elimination half-life of metoprolol
      in pericardial fluid was 14.4 min with negligible accumulations in the plasma,
      whereas with IV delivery, the elimination half-life in plasma was 11.1 min with
      negligible amounts found in the pericardial fluid. The targeted intrapericardial
      delivery of metoprolol effectively lowers heart rates for sustained periods of
      time, with minimal effect on either ventricular contractility or mean arterial
      pressure. We did not observe dramatic changes in induced atrial fibrillation
      times or refractory periods using this model.

PMID- 21877258
TI  - Surgery in management of snake envenomation in children.
AB  - BACKGROUND: Snakebite is common in children especially in the developing
      countries. This study was undertaken to determine the role of surgery in the
      treatment of venomous snake bite in pediatric patients. METHODS: The clinical
      data of 58 pediatric patients aged 0-16 years who had been treated for venomous
      snakebite from January 1999 to December 2008 were analyzed. RESULTS: Of the 58
      patients, 43 (74.6%) were male. Peak age incidence was around 2-3 years (28.8%).
      The majority of envenomations occurred in the summer and rainy seasons,
      especially in the latter, during flooding. The bites occurred during 6 pm to 12
      pm in 27 patients (49.0%). The main bite site was the lower extremities in 49
      patients (83.9%). The main species of the snake were Malayan pit viper
      (Calloselasma rhodostoma) in 28 patients (47.5%) and cobra (Ophiophagus hunnah or
      Naja spp.) in 21 patients (35.6%). Soft tissue necrosis occurred more in cobra
      bites (47.6%) than viper bites (3.6%). The most common organism identified in
      necrotic tissue was Morganella morgagnii. Four patients with cobra bite had
      respiratory failure that required ventilatory support. Compartment syndrome was
      suspected in 2 patients. Surgical intervention was necessary in 13 patients. Most
      procedures involved serial wound debridement, followed by skin grafting. One case
      needed a toe amputation because of necrosis. The average length of hospital stay
      in patients who needed surgical management was 18.8 days (range: 12.1-25.5 days).
      There were no mortalities. CONCLUSIONS: Surgery plays an important role in the
      management of snakebite patients, especially for those with cobra bite with
      tissue necrosis.

PMID- 21877260
TI  - Predictive genomic biomarkers.
AB  - Advances in the biological characterization of tumors has led to the design and
      development of anticancer agents targeting specific molecular alterations. The
      majority of these agents are designed to silence phosphorylation signals that are
      required for the development and maintenance of the cancer phenotype in specific
      tumor types. Prospective identification of cancer subsets containing particular
      target alterations is a requirement for these development programs, which in
      theory, should include smaller trials and result in larger therapeutic benefits.
      In this review, we will examine relevant examples of selection markers
      effectively utilized in oncology, and discuss important considerations pertaining
      to the co-development of drugs and diagnostics, including current regulatory
      paths, the incorporation of selection markers emerging late in development, and
      future directions in the area of personalized oncology.

PMID- 21877261
TI  - Magnetite biomineralization in bacteria.
AB  - Magnetotactic bacteria are able to biomineralize magnetic crystals in
      intracellular organelles, so-called "magnetosomes." These particles exhibit
      species- and strain-specific size and morphology. They are of great interest for
      biomimetic nanotechnological and biotechnological research due to their fine
      tuned magnetic properties and because they challenge our understanding of the
      classical principles of crystallization. Magnetotactic bacteria use these highly
      optimized particles, which form chains within the bacterial cells, as a magnetic
      field actuator, enabling them to navigate. In this chapter, we discuss the
      current biological and chemical knowledge of magnetite biomineralization in these
      bacteria. We highlight the extraordinary properties of magnetosomes and some
      resulting potential applications.

PMID- 21877263
TI  - Manganese oxidation by bacteria: biogeochemical aspects.
AB  - Manganese is an essential trace metal that is not as readily oxidizable like
      iron. Several bacterial groups posses the ability to oxidize Mn effectively
      competing with chemical oxidation. The oxides of Mn are the strongest of the
      oxidants, next to oxygen in the aquatic environment and therefore control the
      fate of several elements. Mn oxidizing bacteria have a suit of enzymes that not
      only help to scavenge Mn but also other associated elements, thus playing a
      crucial role in biogeochemical cycles. This article reviews the importance of
      manganese and its interaction with microorganisms in the oxidative Mn cycle in
      aquatic realms.

PMID- 21877262
TI  - Maxi- and mini-ferritins: minerals and protein nanocages.
AB  - Ferritins synthesize ferric oxide biominerals and are central to all life for
      concentrating iron and protection against oxidative stress from the ferrous and
      oxidant chemistry. The ferritin protein nanocages and biomineral synthesis are
      discussed in terms of wide biological distribution of the maxi-ferritins (24
      subunit +/- heme) and mini-ferritins (Dps) (12 subunit), conservations of the
      iron/oxygen catalytic sites in the protein cages, mineral formation (step i.
      Fe(II) entry and binding, step ii. O(2) or H(2)O(2) binding and formation of
      transition intermediates, step iii. release of differric oxo mineral precursors
      from active sites, step iv. nucleation and mineralization) properties of the
      minerals, and protein control of mineral dissolution and release of Fe(II). Pores
      in ferritin protein cages control iron entry for mineralization and iron exit
      after mineral dissolution. The relationship between phosphate or the presence of
      catalytically inactive subunits (animal L subunits) and ferritin iron mineral
      disorder is developed based on new information about contributions of ferritin
      protein cage structure to nucleation in protein cage subunit channels that exit
      close enough to those of other subunits and exiting mineral nuclei to facilitate
      bulk mineral formation. How and where protons move in and out of the protein
      during mineral synthesis and dissolution, how ferritin cage assembly with 12 or
      24 subunits is encoded in the widely divergent ferritin amino acid sequences, and
      what is the role of the protein in synthesis of the bulk mineral are all
      described as problems requiring new approaches in future investigations of
      ferritin biominerals.

PMID- 21877264
TI  - Molecular biomineralization: toward an understanding of the biogenic origin of
      polymetallic nodules, seamount crusts, and hydrothermal vents.
AB  - Polymetallic nodules and crusts, hydrothermal vents from the Deep Sea are
      economically interesting, since they contain alloying components, e.g., manganese
      or cobalt, that are used in the production of special steels; in addition, they
      contain rare metals applied for plasma screens, for magnets in hard disks, or in
      hybrid car motors. While hydrothermal vents can regenerate in weeks, polymetallic
      nodules and seamount crusts grow slowly. Even though the geochemical basis for
      the growth of the nodules and crusts has been well studied, the contribution of
      microorganisms to the formation of these minerals remained obscure. Recent HR-SEM
      (high-resolution scanning electron microscopy) analyses of nodules and crusts
      support their biogenic origin. Within the nodules, bacteria with surface S-layers
      are arranged on biofilm-like structures, around which Mn deposition starts. In
      crusts, coccoliths represent the dominant biologically formed structures that act
      as bio-seeds for an initial Mn deposition. In contrast, hydrothermal vents have
      apparently an abiogenic origin; however, their minerals are biogenically
      transformed by bacteria. In turn, strategies can now be developed for
      biotechnological enrichment as well as selective dissolution of metals from such
      concretions. We are convinced that the recent discoveries will considerably
      contribute to our understanding of the participation of organic matrices in the
      enrichment of those metals and will provide the basis for feasibility studies for
      biotechnological applications.

PMID- 21877259
TI  - Signaling pathways mediating alcohol effects.
AB  - Ethanol's effects on intracellular signaling pathways contribute to acute effects
      of ethanol as well as to neuroadaptive responses to repeated ethanol exposure. In
      this chapter we review recent discoveries that demonstrate how ethanol alters
      signaling pathways involving several receptor tyrosine kinases and intracellular
      tyrosine and serine-threonine kinases, with consequences for regulation of cell
      surface receptor function, gene expression, protein translation, neuronal
      excitability and animal behavior. We also describe recent work that demonstrates
      a key role for ethanol in regulating the function of scaffolding proteins that
      organize signaling complexes into functional units. Finally, we review recent
      exciting studies demonstrating ethanol modulation of DNA and histone modification
      and the expression of microRNAs, indicating epigenetic mechanisms by which
      ethanol regulates neuronal gene expression and addictive behaviors.

PMID- 21877265
TI  - Molecular basis of bacterial calcium carbonate precipitation.
AB  - Calcium carbonate precipitation is a widespread process, occurring in different
      bacterial taxonomic groups and in different environments, at a scale ranging from
      the microscopic one of cells to that of geological formations. It has relevant
      implications in natural processes and has great potentiality in numerous
      applications. For these reasons, bacterial precipitation has been investigated
      extensively both in natural environments and under laboratory conditions.
      Different mechanisms of bacterial involvement in precipitation have been
      proposed. There is an agreement that the phenomenon can be influenced by the
      environmental physicochemical conditions and it is correlated both to the
      metabolic activity and the cell surface structures of microorganisms.
      Nevertheless, the role played by bacteria in calcium mineralization remains a
      matter of debate. This chapter reviews the main mechanisms of the process with
      particular focus on what is known on molecular aspects, and discusses the
      significance of the precipitation event also from an evolutionary point of view.

PMID- 21877266
TI  - Principles of calcium-based biomineralization.
AB  - The chapter provides some basic information on the formation principles of
      calcium carbonate in biological systems in marine environment in the point of
      view of materials science in order to provide strategies for biomimetic design
      and preparation of new functional materials. Many researchers try to explain the
      principles of biomineralization and get some valuable conclusions. This chapter
      introduces some calcium-based biominerals in aquatic organisms which mainly
      include calcium carbonate and calcium phosphate. Then it gives a presentation of
      the hierarchical structure of calcium carbonate-based and calcium phosphate-based
      biominerals, e.g., mollusc shell, pearl, carp otolith, tooth, and bone. Moreover,
      the chapter explains the principles of calcium carbonate mineralization from the
      aspects of the effects of additives and templates; it also gives some
      explanations to the principles of calcium phosphate mineralization.

PMID- 21877267
TI  - Molecular aspects of biomineralization of the echinoderm endoskeleton.
AB  - Echinoderms possess a rigid endoskeleton composed of calcite and small amounts of
      occluded organic matrix proteins. The test (i.e., the shell-like structure of
      adults), spines, pedicellariae, tube feet, and teeth of adults, as well as
      delicate endoskeletal spicules found in larvae of some classes, are the main
      skeletal structures. They have been intensively studied for insight into the
      mechanisms of biomineralization. Recent work on characterization of the mineral
      phase and occluded proteins in embryonic skeletal spicules shows that these
      simple-looking structures contain scores of different proteins, and that the
      mineral phase is composed of amorphous calcium carbonate (ACC), which then
      transforms to an anhydrous ACC and eventually to calcite. Likewise, the adult
      tooth shows a similar transition from hydrated ACC to anhydrous ACC to calcite
      during its formation, and a similar transition is likely occurring during adult
      spine regeneration. We speculate that: (1) the ACC precursor is a general
      strategy employed in biomineralization in echinoderms, (2) the numerous occluded
      proteins play a role in post-secretion formation of the mature biomineralized
      structure, and (3) proteins with "multi-valent" intrinsically disordered domains
      are important for formation of occluded matrix structures, and regulation of
      crucial matrix-mineral interactions, such as ACC to calcite transitions and
      polymorph selection.

PMID- 21877268
TI  - Echinoderms as blueprints for biocalcification: regulation of skeletogenic genes
      and matrices.
AB  - Echinoderms have an extensive endoskeleton composed of magnesian calcite, a form
      of calcium carbonate that contains small amounts of magnesium carbonate and
      occluded matrix proteins. Adult sea urchins have several calcified structures,
      including test, teeth, and spines, composed of numerous ossicles which form a
      three-dimensional meshwork of mineral trabeculae, the stereom. The biomineral
      development begins in 24-hour-old embryos within the primary mesenchyme cells
      (PMCs), the only cells producing a set of necessary matrix proteins. The
      deposition of the biomineral occurs in a privileged extracellular space produced
      by the fused filopodial processes of the PMCs. We showed for the first time that
      signals from ectoderm cells overlying PMCs play an important role in the
      regulation of biomineralization-related genes. It is believed that growth factors
      are produced by ectoderm cells and released into the blastocoel where they
      interact with cognate receptor tyrosine kinases restricted to PMCs, which
      activate signaling cascades regulating the expression of biomineralization
      related genes. We demonstrated the implication of a TGF-beta family factor by a
      perturbation model in which skeleton elongation was indirectly blocked by
      monoclonal antibodies to an extracellular matrix (ECM) protein located on the
      apical surface of ectoderm. Thus, it was inferred that interfering with the
      binding of the ECM ligand, a member of the discoidin family, to its cell surface
      receptor, a betaC integrin, disrupts the ectodermal cell signaling cascade,
      resulting in reduced or aberrant skeletons. During the last few years, we
      analyzed the expression of biomineralization-related genes in other examples of
      experimentally induced skeleton malformations, produced by the exposure to toxic
      metals, such as Cd and Mn or ionizing radiations, such as UV-B and X-rays.
      Besides the obvious toxicological implication, since the mis-expression of
      spicule matrix genes paralleled skeleton defects, we believe that by means of
      these studies we can dissect the molecular steps taking place and possibly
      understand the physiological events regulating embryonic biomineralization.

PMID- 21877269
TI  - The unique invention of the siliceous sponges: their enzymatically made bio
      silica skeleton.
AB  - Sponges are sessile filter feeders that, among the metazoans, evolved first on
      Earth. In the two classes of the siliceous sponges (the Demospongiae and the
      Hexactinellida), the complex filigreed body is stabilized by an inorganic
      skeleton composed of amorphous silica providing them a distinct body shape and
      plan. It is proposed that the key innovation that allowed the earliest metazoans
      to form larger specimens was the enzyme silicatein. This enzyme is crucial for
      the formation of the siliceous skeleton. The first sponge fossils with body
      preservation were dated back prior to the "Precambrian-Cambrian" boundary
      [Vendian (610-545 Ma)/Ediacaran (542-580 Ma)]. A further molecule required for
      the formation of a hard skeleton was collagen, fibrous organic filaments that
      need oxygen for their formation. Silicatein forming the spicules and collagen
      shaping their morphology are the two organic components that control the
      appositional growth of these skeletal elements. This process starts in both
      demosponges and hexactinellids intracellularly and is completed extracellularly
      where the spicules may reach sizes of up to 3 m. While the basic strategy of
      their formation is identical in both sponge classes, it differs on a
      substructural level. In Hexactinellida, the initial silica layers remain
      separated, those layers bio-fuse (bio-sinter) together in demosponges. In some
      sponge taxa, e.g., the freshwater sponges from the Lake Baikal, the individual
      spicules are embedded in an organic matrix that is composed of the DUF protein.
      This protein comprises clustered stretches of amino acid sequences composed of
      pronounced hydrophobic segments, each spanning around 35 aa. We concluded with
      the remark of Thompson (1942) highlighting that "the sponge-spicule is a typical
      illustration of the theory of 'bio-crystallisation' to form 'biocrystals' ein
      Mittelding between an inorganic crystal and an organic secretion." Moreover, the
      understanding of the enzymatic formation of the spicules conferred sponge
      biosilica a considerable economical actuality as a prime raw material of this
      millennium.

PMID- 21877270
TI  - Biosilica-based strategies for treatment of osteoporosis and other bone diseases.
AB  - Osteoporosis is a common disease in later life, which has become a growing public
      health problem. This degenerative bone disease primarily affects postmenopausal
      women, but also men may suffer from reduced bone mineral density. The development
      of prophylactic treatments and medications of osteoporosis has become an urgent
      issue due to the increasing proportion of the elderly in the population. Apart
      from medical/hormonal treatments, current strategies for prophylaxis of
      osteoporosis are primarily based on calcium supplementation as a main constituent
      of bone hydroxyapatite mineral. Despite previous reports suggesting an essential
      role in skeletal growth and development, the significance of the trace element
      silicon in human bone formation has attracted major scientific interest only
      rather recently. The interest in silicon has been further increased by the latest
      discoveries in the field of biosilicification, the formation of the inorganic
      silica skeleton of the oldest still extant animals on Earth, the sponges, which
      revealed new insights in the biological function of this element. Sponges make
      use of silicon to build up their inorganic skeleton which consists of biogenously
      formed polymeric silica (biosilica). The formation of biosilica is mediated by
      specific enzymes, silicateins, which have been isolated, characterized, and
      expressed in a recombinant way. Epidemiological studies revealed that dietary
      silicon reduces the risk of osteoporosis and other bone diseases. Recent results
      allowed for the first time to understand the molecular mechanism underlying the
      protective effect of silicic acid/biosilica against osteoporosis. Biosilica was
      shown to modulate the ratio of expression of two cytokines involved in bone
      formation-RANKL and osteoprotegerin. Hence, biosilica has been proposed to have a
      potential in prophylaxis and therapy of osteoporosis and related bone diseases.

PMID- 21877271
TI  - Structure and function of matrix proteins and peptides in the biomineral
      formation in crustaceans.
AB  - Crustaceans have hard cuticle with layered structure, which is composed mainly of
      chitin, proteins, and calcium carbonate. Crustaceans grow by shedding the old
      cuticle and replacing it with a new one. Decalcification in the cuticle during
      the pre-molt stage and concomitant calcification in the stomach to form
      gastroliths observed in some crustacean species are triggered by the molting
      hormone. Various proteins and peptides have been identified from calcified
      cuticle and gastroliths, and their functions have been examined in terms of
      calcification and interaction with chitin. Acidic nature of matrix proteins is
      important for recruitment of calcium ions and interaction with calcium carbonate.
      Examination of the relationship between amino acid sequence containing acidic
      amino acid residues and calcification inhibitory activity revealed that the
      potency did not depend on the sequence but on the number of acidic amino acid
      residues. Calcium carbonate in the calcified tissues of crustaceans is amorphous
      in many cases. Crustaceans take a strategy to induce and maintain amorphous
      calcium carbonate by using low-molecular-weight phosphorus compounds.

PMID- 21877272
TI  - Molecular approaches to understand biomineralization of shell nacreous layer.
AB  - The nacreous layer of molluskan shells, which consists of highly oriented
      aragonitic crystals and an organic matrix (including chitin and proteins), is a
      product of biomineralization. This paper briefly introduces the recent research
      advances on nacre biomineralization of shells from bivalves and gastropods, which
      mainly focus on analysis of the micro- and nano-structure and components of shell
      nacreous layers, and investigations of the characteristics and functions of
      matrix proteins from nacre. Matrix proteins not only participate in construction
      of the organic nacre framework, but also control the nucleation and growth of
      aragonitic crystals, as well as determine the polymorph specificity of calcium
      carbonate in nacre. Moreover, the inorganic aragonite phase also plays an active
      role in organizing nacre microstructure. Based on these studies, several models
      to illustrate the formation mechanism related to lamellar nacre in bivalves, and
      columnar nacre in gastropods are introduced.

PMID- 21877273
TI  - Acidic Shell Proteins of the Mediterranean Fan Mussel Pinna nobilis.
AB  - In molluscs, the shell secretion process is controlled by a set of extracellular
      macromolecules collectively called the shell matrix. The shell matrix, which is
      produced by the mantle epithelial cells during mineralization, is predominantly
      composed of proteins, glycoproteins, acidic polysaccharides, and chitin that
      precisely regulate the deposition of calcium carbonate outside the mantle cells.
      In the present paper, we focus on the shell of Pinna nobilis, the giant
      Mediterranean fan mussel, usually considered as a model for studying molluscan
      biomineralization processes. P. nobilis exhibits indeed a nacro-prismatic shell,
      the outer layer of which is constituted of the so-called "regular simple calcitic
      prisms," according to Carter and Clark (1985). We review here the microstructural
      characteristics of the prisms and nacre and the biochemical properties of their
      associated matrices. In particular, the calcitic prisms of P. nobilis are
      characterized by a cortege of unusually acidic intraprismatic proteins, while the
      ones of the nacreous layer seem less acidic. A brief description of the molecular
      characterization of three acidic proteins, caspartin, calprismin and mucoperlin,
      is given. In particular, we show that extremely acidic intracrystalline proteins
      such as caspartin interact with calcium carbonate at different scales, from
      micrometric to crystal lattice levels.

PMID- 21877274
TI  - Analysis of protein-protein interactions using high-throughput yeast two-hybrid
      screens.
AB  - The yeast two-hybrid (Y2H) system is a powerful tool to identify binary protein
      protein interactions. Here, we describe array-based two-hybrid methods that use
      defined libraries of open reading frames (ORFs) and pooled prey library
      screenings that use random genomic or cDNA libraries. The array-based Y2H system
      is well-suited for interactome studies of existing ORFeomes or subsets thereof,
      preferentially in a recombination-based cloning system. Array-based Y2H screens
      efficiently reduce false positives by using built-in controls, retesting, and
      evaluation of background activation. Hands-on time and the amount of used
      resources grow exponentially with the number of tested proteins; this is a
      disadvantage for large genome sizes. For large genomes, random library screen may
      be more efficient in terms of time and resources, but not as comprehensive as
      array screens, and it requires significant sequencing capacity. Furthermore,
      multiple variants of the Y2H vector systems detect markedly different subsets of
      interactions in the same interactome. Hence, only multiple variations of the Y2H
      systems ensure comprehensive coverage of an interactome.

PMID- 21877275
TI  - Identification of mammalian protein complexes by lentiviral-based affinity
      purification and mass spectrometry.
AB  - Protein complexes and protein-protein interactions (PPIs) are fundamental for
      most biological functions. Deciphering the extensive protein interaction networks
      that occur within cellular contexts has become a logical extension to the human
      genome project. Proteome-scale interactome analysis of mammalian systems requires
      efficient methods for accurately detecting PPIs with specific considerations for
      the intrinsic technical challenges of mammalian genome manipulation. In this
      chapter, we outline in detail an innovative lentiviral-based functional proteomic
      approach that can be used to rapidly characterize protein complexes from a broad
      range of mammalian cell lines. This method integrates the following key features:
      (1) lentiviral elements for efficient delivery of tagged constructs into
      mammalian cell lines; (2) site-specific GatewayTM recombination sites for easy
      cloning; (3) versatile epitope-tagging system for flexible affinity purification
      strategies; and (4) LC-MS-based protein identification using tandem mass
      spectrometry.

PMID- 21877276
TI  - Protein networks involved in vesicle fusion, transport, and storage revealed by
      array-based proteomics.
AB  - Secretagogin is a calcium-binding protein whose expression is characterised in
      neuroendocrine, pancreatic, and retinal cells. We have used an array-based
      proteomic approach with the prokaryotically expressed human protein array (hEx1)
      and the eukaryotically expressed human protein array (Protoarray) to identify
      novel calcium-regulated interaction networks of secretagogin. Screening of these
      arrays with fluorophore-labelled secretagogin in the presence of Ca(2+) ions led
      to the identification of 12 (hEx1) and 6 (Protoarray) putative targets. A number
      of targets were identified in both array screens. The putative targets from the
      hEx1 array were expressed, purified, and subjected to binding analysis using
      surface plasmon resonance. This identified binding affinities for nine novel
      secretagogin targets with equilibrium dissociation constants in the 100 pM to 10
      nM range. Six of the novel target proteins have important roles in vesicle
      trafficking; SNAP-23, ARFGAP2, and DOC2alpha are involved in regulating fusion of
      vesicles to membranes, kinesin 5B and tubulin are essential for transport of
      vesicles in the cell, and rootletin builds up the rootlet, which is believed to
      function as scaffold for vesicles. Among the targets are two enzymes, DDAH-2 and
      ATP-synthase, and one oncoprotein, myeloid leukaemia factor 2. This screening
      method identifies a role for secretagogin in secretion and vesicle trafficking
      interacting with several proteins integral to these processes.

PMID- 21877277
TI  - Identification and relative quantification of native and proteolytically
      generated protein C-termini from complex proteomes: C-terminome analysis.
AB  - Proteome-wide analysis of protein C-termini has long been inaccessible, but is
      now enabled by a newly developed negative selection strategy we term C
      terminomics. In this procedure, amine- and carboxyl groups of full-length
      proteins are chemically protected. After trypsin digestion, N-terminal and
      internal tryptic peptides - but not C-terminal peptides - posses newly formed,
      unprotected C-termini that are removed by coupling to the high-molecular-weight
      polymer poly-allylamine. Ultrafiltration separates the uncoupled, blocked C
      terminal peptides that are subsequently analyzed by liquid chromatography-tandem
      mass spectrometry. On a proteome-wide scale, this strategy profiles native
      protein C-termini together with neo C-termini generated by endoproteolytic
      cleavage or processive C-terminal truncations ("ragging"). In bacterial
      proteomes, hundreds of protein C-termini were identified. Stable isotope labeling
      enables -quantitative comparison of protein C-termini and C-terminal processing
      in different samples. Using formaldehyde-based chemical labeling, this
      quantitative approach termed "carboxy-terminal amine-based isotope labeling of
      substrates (C-TAILS)" identified >100 cleavage sites of exogenously applied GluC
      protease in an Escherichia coli proteome. C-TAILS complements recently developed
      N-terminomic techniques for endoprotease substrate discovery and is essential for
      the characterization of carboxyprotease processing.

PMID- 21877278
TI  - Construction of protein interaction networks based on the label-free quantitative
      proteomics.
AB  - Multiprotein complexes are essential building blocks for many cellular processes
      in an organism. Taking the process of transcription as an example, the interplay
      of several chromatin-remodeling complexes is responsible for the tight regulation
      of gene expression. Knowing how those proteins associate into protein complexes
      not only helps to improve our understanding of these cellular processes, but can
      also lead to the discovery of the function of novel interacting proteins. Given
      the large number of proteins with little to no functional annotation throughout
      many organisms, including human, the identification and characterization of
      protein complexes has grown into a major focus of network biology. Toward this
      goal, we have developed several computational approaches based upon label-free
      quantitative proteomics approaches for the analysis of protein complexes and
      protein interaction networks. Here, we describe the computational approaches used
      to build probabilistic protein interaction networks, which are detailed in this
      chapter using the example of complexes involved in chromatin remodeling and
      transcription.

PMID- 21877279
TI  - Studying binding specificities of peptide recognition modules by high-throughput
      phage display selections.
AB  - Peptide recognition modules (PRMs) play critical roles in cellular processes,
      including differentiation, proliferation and cytoskeleton organization. PRMs
      normally bind to short linear motifs in protein ligands, and by so doing recruit
      proteins into signaling complexes. Based on the binding specificity profile of a
      PRM, one can predict putative natural interaction partners by searching genome
      databases. Candidate interaction partners can in turn provide clues to assemble
      potential in vivo protein complexes that the PRM may be involved with.
      Combinatorial peptide libraries have proven to be effective tools for profiling
      the binding specificities of PRMs. Herein, we describe high-throughput methods
      for the expression and purification of PRM proteins and the use of peptide-phage
      libraries for PRM specificity profiling. These high-throughput methods greatly
      expedite the study of PRM families on a genome-wide scale.

PMID- 21877280
TI  - Array-based synthetic genetic screens to map bacterial pathways and functional
      networks in Escherichia coli.
AB  - Cellular processes are carried out through a series of molecular interactions.
      Various experimental approaches can be used to investigate these functional
      relationships on a large-scale. Recently, the power of investigating biological
      systems from the perspective of genetic (gene-gene, or epistatic) interactions
      has been evidenced by the ability to elucidate novel functional relationships.
      Examples of functionally related genes include genes that buffer each other's
      function or impinge on the same biological process. Genetic interactions have
      traditionally been investigated in bacteria by combining pairs of mutations (for
      example, gene deletions) and assessing deviation of the phenotype of each double
      mutant from an expected neutral (or no interaction) phenotype. Fitness is a
      particularly convenient phenotype to measure: when the double mutant grows faster
      or slower than expected, the two mutated genes are said to show alleviating or
      aggravating interactions, respectively. The most commonly used neutral model
      assumes that the fitness of the double mutant is equal to the product of
      individual single mutant fitness. A striking genetic interaction is exemplified
      by the loss of two nonessential genes that buffer each other in performing an
      essential biological function: deleting only one of these genes produces no
      detectable fitness defect; however, loss of both genes simultaneously results in
      systems failure, leading to synthetic sickness or lethality. Systematic large
      scale genetic interaction screens have been used to generate functional maps for
      model eukaryotic organisms, such as yeast, to describe the functional
      organization of gene products into pathways and protein complexes within a cell.
      They also reveal the modular arrangement and cross-talk of pathways and complexes
      within broader functional neighborhoods (Dixon et al. Annu Rev Genet 43:601-625,
      2009). Here, we present a high-throughput quantitative Escherichia coli synthetic
      genetic array (eSGA) screening procedure, which we developed to systematically
      infer genetic interactions by scoring growth defects among large numbers of
      double mutants in a classic gram-negative bacterium. The eSGA method exploits the
      rapid colony growth, ease of genetic manipulation, and natural efficient genetic
      exchange via conjugation of laboratory E. coli strains. Replica pinning is used
      to grow and mate arrayed sets of single-gene mutant strains as well as to select
      double mutants en mass. Strain fitness, which is used as the eSGA readout, is
      quantified by the digital imaging of the plates and subsequent measuring and
      comparing single and double mutant colony sizes. While eSGA can be used to screen
      select mutants to probe the functions of individual genes; using eSGA more
      broadly to collect genetic interaction data for many combinations of genes can
      help reconstruct a functional interaction network to reveal novel links and
      components of biological pathways as well as unexpected connections between
      pathways. A variety of bacterial systems can be investigated, wherein the genes
      impinge on a essential biological process (e.g., cell wall assembly, ribosome
      biogenesis, chromosome replication) that are of interest from the perspective of
      drug development (Babu et al. Mol Biosyst 12:1439-1455, 2009). We also show how
      genetic interactions generated by high-throughput eSGA screens can be validated
      by manual small-scale genetic crosses and by genetic complementation and gene
      rescue experiments.

PMID- 21877281
TI  - Advanced methods for high-throughput microscopy screening of genetically modified
      yeast libraries.
AB  - High-throughput methodologies have created new opportunities for studying
      biological phenomena in an unbiased manner. Using automated cell manipulations
      and microscopy platforms, it is now possible to easily screen entire genomes for
      genes that affect any cellular process that can be visualized. The onset of these
      methodologies promises that the near future will bring with it a more
      comprehensive and richly integrated understanding of complex and dynamic cellular
      structures and processes. In this review, we describe how to couple systematic
      genetic tools in the budding yeast Saccharomyces cerevisiae alongside robotic
      visualization systems to attack biological questions. The combination of high
      throughput microscopy screens with the powerful, yet simple, yeast model system
      for studying the eukaryotic cell should pioneer new knowledge in all areas of
      cell biology.

PMID- 21877282
TI  - Pooled lentiviral shRNA screening for functional genomics in mammalian cells.
AB  - Genome sequencing efforts have reformed the nature of biological inquiry,
      prompting the development of technologies for the functional annotation of
      mammalian genes. Based on methodologies originally discovered in plants and
      Caenorhabditis elegans, RNA interference has offered cell biologists an effective
      and reproducible approach to perturb gene function in mammalian cells and whole
      organisms. Initial application of RNA interference libraries targeting the human
      and mouse genomes relied on arrayed screening approaches, whereby each unique RNA
      interference reagent is arrayed into individual wells of a microtiter plate.
      These screens are not trivial to perform, requiring a substantial investment in
      infrastructure. In the past decade, many technological advances have been made
      that make genome-wide RNA interference screening more accessible to researchers
      and more feasible to perform in nonspecialized laboratories. Here, we describe a
      comprehensive protocol for pooled short-hairpin RNA screening, including
      methodologies for pooled lentivirus production, cell infection, genome-wide
      negative selection screening and resources for pooled screen deconvolution, and
      data analysis. As a technique, pooled shRNA screening is still in its infancy,
      but the methodology has already been successfully applied to probe diverse
      signaling pathways, as a means of drug target identification, and to identify
      essential genes in normal and cancer cell lines.

PMID- 21877283
TI  - Plant DNA sequencing for phylogenetic analyses: from plants to sequences.
AB  - DNA sequences are important sources of data for phylogenetic analysis. Nowadays,
      DNA sequencing is a routine technique in molecular biology laboratories. However,
      there are specific questions associated with project design and sequencing of
      plant samples for phylogenetic analysis, which may not be familiar to researchers
      starting in the field. This chapter gives an overview of methods and protocols
      involved in the sequencing of plant samples, including general recommendations on
      the selection of species/taxa and DNA regions to be sequenced, and field
      collection of plant samples. Protocols of plant sample preparation, DNA
      extraction, PCR and cloning, which are critical to the success of molecular
      phylogenetic projects, are described in detail. Common problems of sequencing
      (using the Sanger method) are also addressed. Possible applications of second
      generation sequencing techniques in plant phylogenetics are briefly discussed.
      Finally, orientation on the preparation of sequence data for phylogenetic
      analyses and submission to public databases is also given.

PMID- 21877284
TI  - Using coevolution to predict protein-protein interactions.
AB  - Bioinformatic methods to predict protein-protein interactions (PPI) via
      coevolutionary analysis have -positioned themselves to compete alongside
      established in vitro methods, despite a lack of understanding for the underlying
      molecular mechanisms of the coevolutionary process. Investigating the alignment
      of coevolutionary predictions of PPI with experimental data can focus the
      effective scope of prediction and lead to better accuracies. A new rate-based
      coevolutionary method, MMM, preferentially finds obligate interacting proteins
      that form complexes, conforming to results from studies based on
      coimmunoprecipitation coupled with mass spectrometry. Using gold-standard
      databases as a benchmark for accuracy, MMM surpasses methods based on abundance
      ratios, suggesting that correlated evolutionary rates may yet be better than
      coexpression at predicting interacting proteins. At the level of protein domains,
      -coevolution is difficult to detect, even with MMM, except when considering small
      scale experimental data involving proteins with multiple domains. Overall, these
      findings confirm that coevolutionary -methods can be confidently used in
      predicting PPI, either independently or as drivers of coimmunoprecipitation
      experiments.

PMID- 21877285
TI  - Visualizing gene-set enrichment results using the Cytoscape plug-in enrichment
      map.
AB  - Gene-set enrichment analysis finds functionally coherent gene-sets, such as
      pathways, that are statistically overrepresented in a given gene list. Ideally,
      the number of resulting sets is smaller than the number of genes in the list,
      thus simplifying interpretation. However, the increasing number and redundancy of
      -gene-sets used by many current enrichment analysis resources work against this
      ideal. "Enrichment Map" is a Cytoscape plug-in that helps overcome gene-set
      redundancy and aids in the interpretation of enrichment results. Gene-sets are
      organized in a network, where each set is a node and links represent gene overlap
      between sets. Automated network layout groups related gene-sets into -network
      clusters, enabling the user to quickly identify the major enriched functional
      themes and more easily interpret enrichment results.

PMID- 21877286
TI  - Quality control methodology for high-throughput protein-protein interaction
      screening.
AB  - Protein-protein interactions are key to many aspects of the cell, including its
      cytoskeletal structure, the signaling processes in which it is involved, or its
      metabolism. Failure to form protein complexes or signaling cascades may sometimes
      translate into pathologic conditions such as cancer or neurodegenerative
      diseases. The set of all protein interactions between the proteins encoded by an
      organism constitutes its protein interaction network, representing a scaffold for
      biological function. Knowing the protein interaction network of an organism,
      combined with other sources of biological information, can unravel fundamental
      biological circuits and may help better understand the molecular basics of human
      diseases. The protein interaction network of an organism can be mapped by
      combining data obtained from both low-throughput screens, i.e., "one gene at a
      time" experiments and high-throughput screens, i.e., screens designed to
      interrogate large sets of proteins at once. In either case, quality controls are
      required to deal with the inherent imperfect nature of experimental assays. In
      this chapter, we discuss experimental and statistical methodologies to quantify
      error rates in high-throughput protein-protein interactions screens.

PMID- 21877287
TI  - Filtering and interpreting large-scale experimental protein-protein interaction
      data.
AB  - Rarely acting in isolation, it is invariably the physical associations among
      proteins that define their biological activity, necessitating the study of the
      cellular meshwork of protein-protein interactions (PPI) before a full
      appreciation of gene function can be achieved. The past few years have seen a
      marked expansion in the both the sheer volume and number of organisms for which
      high-quality interaction data is available, with high-throughput interaction
      screening and detection techniques showing consistent improvement both in scale
      and sensitivity. Although techniques for large-scale PPI mapping are increasingly
      being applied to new organisms, including human, there is a corresponding need to
      rigorously evaluate, benchmark, and impartially filter the results. This chapter
      explores methods for PPI dataset evaluation, including a survey of previous
      techniques applied by landmark studies in the field and a discussion of promising
      new experimental approaches. We further outline practical suggestions and useful
      tools for interpreting newly generated PPI data. As the majority of large-scale
      experimental data has been generated for the budding yeast S. cerevisiae, most of
      the techniques and datasets described are from the perspective of this model
      unicellular eukaryote; however, extensions to other organisms including mammals
      are mentioned where possible.

PMID- 21877288
TI  - Classification of cancer patients using pathway analysis and network clustering.
AB  - Molecular expression patterns have often been used for patient classification in
      oncology in an effort to improve prognostic prediction and treatment
      compatibility. This effort is, however, hampered by the highly heterogeneous data
      often seen in the molecular analysis of cancer. The lack of overall similarity
      between expression profiles makes it difficult to partition data using
      conventional data mining tools. In this chapter, the authors introduce a
      bioinformatics protocol that uses REACTOME pathways and patient-protein network
      structure (also called topology) as the basis for patient classification.

PMID- 21877289
TI  - Statistical analysis of dynamic transcriptional regulatory network structure.
AB  - Here, we present a detailed method for generating a dynamic transcriptional
      regulatory network from large-scale chromatin immunoprecipitation data, and
      functional analysis of participating factors through the identification and
      characterization of significantly overrepresented multi-input motifs in the
      network. This is done by visualizing interactive data using a network analysis
      tool, such as Cytoscape, clustering DNA targets of the transcription factors
      based on their network topologies, and statistically analyzing each cluster based
      on its size and properties of its members. These analyses yield testable
      predictions about the conditional and cooperative functions of the factors. This
      is a versatile approach that allows the visualization of network architecture on
      a genome-wide level and is applicable to understanding combinatorial control
      mechanisms of DNA-binding regulators that conditionally cooperate in a wide
      variety of biological models.

PMID- 21877290
TI  - Imputing and predicting quantitative genetic interactions in epistatic MAPs.
AB  - Mapping epistatic (or genetic) interactions has emerged as an important network
      biology approach for establishing functional relationships among genes and
      proteins. Epistasis networks are complementary to physical protein interaction
      networks, providing valuable insight into both the function of individual genes
      and the overall wiring of the cell. A high-throughput method termed "epistatic
      mini array profiles" (E-MAPs) was recently developed in yeast to quantify
      alleviating or aggravating interactions between gene pairs. The typical output of
      an E-MAP experiment is a large symmetric matrix of interaction scores. One
      problem with this data is the large amount of missing values - interactions that
      cannot be measured during the high-throughput process or whose measurements were
      discarded due to quality filtering steps. These missing values can reduce the
      effectiveness of some data analysis techniques and prevent the use of others.
      Here, we discuss one solution to this problem, imputation using nearest
      neighbors, and give practical examples of the use of a freely available
      implementation of this method.

PMID- 21877291
TI  - Displaying chemical information on a biological network using Cytoscape.
AB  - Cytoscape is an open-source software package that is widely used to integrate and
      visualize diverse data sets in biology. This chapter explains how to use
      Cytoscape to integrate open-source chemical information with a biological
      network. By visualizing information about known compound-target interactions in
      the context of a biological network of interest, one can rapidly identify novel
      avenues to perturb the system with compounds and, for example, potentially
      identify therapeutically relevant targets. Herein, two different protocols are
      explained in detail, with no prior knowledge of Cytoscape assumed, which
      demonstrate how to incorporate data from the ChEMBL database with either a gene
      gene or a protein-protein interaction network. ChEMBL is a very large, open
      source repository of compound-target information available from the European
      Molecular Biology Laboratory.

PMID- 21877292
TI  - Modeling of proteins and their assemblies with the integrative modeling platform.
AB  - To understand the workings of the living cell, we need to characterize protein
      assemblies that constitute the cell (for example, the ribosome, 26S proteasome,
      and the nuclear pore complex). A reliable high-resolution structural
      characterization of these assemblies is frequently beyond the reach of current
      experimental methods, such as X-ray crystallography, NMR spectroscopy, electron
      microscopy, footprinting, chemical cross-linking, FRET spectroscopy, small-angle
      X-ray scattering, and proteomics. However, the information garnered from
      different methods can be combined and used to build computational models of the
      assembly structures that are consistent with all of the available datasets. Here,
      we describe a protocol for this integration, whereby the information is converted
      to a set of spatial restraints and a variety of optimization procedures can be
      used to generate models that satisfy the restraints as much as possible. These
      generated models can then potentially inform about the precision and accuracy of
      structure determination, the accuracy of the input datasets, and further data
      generation. We also demonstrate the Integrative Modeling Platform (IMP) software,
      which provides the necessary computational framework to implement this protocol,
      and several applications for specific-use cases.

PMID- 21877293
TI  - Predicting node characteristics from molecular networks.
AB  - A large number of genome-scale networks, including protein-protein and genetic
      interaction networks, are now available for several organisms. In parallel, many
      studies have focused on analyzing, characterizing, and modeling these networks.
      Beyond investigating the topological characteristics such as degree distribution,
      clustering coefficient, and average shortest-path distance, another area of
      particular interest is the prediction of nodes (genes) with a given
      characteristic (labels) - for example prediction of genes that cause a particular
      phenotype or have a given function. In this chapter, we describe methods and
      algorithms for predicting node labels from network-based datasets with an
      emphasis on label propagation algorithms (LPAs) and their relation to local
      neighborhood methods.

PMID- 21877294
TI  - Mathematical modeling of biomolecular network dynamics.
AB  - Mathematical and computational models have become indispensable tools for
      integrating and interpreting heterogeneous biological data, understanding
      fundamental principles of biological system functions, genera-ting reliable
      testable hypotheses, and identifying potential diagnostic markers and therapeutic
      targets. Thus, such tools are now routinely used in the theoretical and
      experimental systematic investigation of biological system dynamics. Here, we
      discuss model building as an essential part of the theoretical and experimental
      analysis of biomolecular network dynamics. Specifically, we describe a procedure
      for defining kinetic equations and parameters of biomolecular processes, and we
      illustrate the use of fractional activity functions for modeling gene expression
      regulation by single and multiple regulators. We further discuss the evaluation
      of model complexity and the selection of an optimal model based on information
      criteria. Finally, we discuss the critical roles of sensitivity, robustness
      analysis, and optimal experiment design in the model building cycle.

PMID- 21877295
TI  - Closed proximal muscle rupture of the biceps brachii in wakeboarders.
AB  - Closed proximal muscle rupture of the biceps brachii is a rare injury. In this
      report, two cases of closed proximal muscle rupture of the biceps brachii after
      wakeboard traumas are described. Both patients presented with a swollen arm,
      weakness during flexion, and a mass in the affected forearm. Magnetic resonance
      imaging showed displacement of the biceps brachii into the forearm. The rupture
      was successfully treated with muscle removal in one case and muscle repair in the
      other. In patients with a wakeboard trauma and similar presentations, closed
      proximal muscle rupture of the biceps brachii should be suspected.

PMID- 21877296
TI  - Navigated knee kinematics after cutting of the ACL and its secondary restraint.
AB  - PURPOSE: The purpose of this study is to evaluate the kinematics changes of the
      knee after cutting of the ACL with or without injury of the anterolateral
      structures. METHODS: In this study, the role of the ACL and one of the secondary
      restraints in controlling knee stability using a navigation system was evaluated.
      The kinematics of the knee was evaluated in different conditions of instability:
      ACL intact, after dissection of the posterolateral (PL) bundle, after dissection
      of the anteromedial (AM) bundle, and after lesion of the lateral capsular
      ligament (LCL). Anterior tibial translation and rotation were measured with a
      computer navigation system in 10 fresh-frozen cadaveric knees by use of a manual
      maximum load. Anterior translation was evaluated at 30 degrees , 60 degrees , and
      90 degrees  of flexion; rotation at 0 degrees , 15 degrees , 30 degrees , 45
      degrees , 60 degrees , and 90 degrees . RESULTS: Cutting the PL bundle does not
      increase anterior translation and rotation of the knee. Cutting the AM bundle
      significantly increased the anteroposterior (AP) translation at 30 degrees  and
      60 degrees  (P = 0.01), but does not increase rotation of the knee. Cutting the
      LCL increased anterior translation at 60 degrees  (P = 0.04) and rotation at 30
      degrees , 45 degrees , and 60 degrees  (P = 0.03). CONCLUSIONS: Within the
      testing conditions of this study, the PL bundle does not affect anterior
      translation and rotation of the knee; the AM bundle is the primary restraint of
      the anterior translation but does not affect rotation of the knee while the
      lesion of the LCL increases tibial rotation and could be related to the pivot
      shift phenomenon, so it is more correct and biomechanical valid to assess and
      repair the associated lesion of the antero-lateral structure of the knee at the
      time of ACL surgery.

PMID- 21877297
TI  - Integrating forensic anthropology into Disaster Victim Identification.
AB  - This paper will provide mass fatality emergency planners, police, medical
      examiners, coroners and other Disaster Victim Identification (DVI) personnel ways
      to integrate forensic anthropologists into DVI operations and demonstrate how
      anthropological contributions have improved DVI projects. In mass disaster
      situations, anthropologists have traditionally been limited to developing
      biological profiles from skeletal remains. Over the past decade, however,
      anthropologists' involvement in DVI has extended well beyond this traditional
      role as they have taken on increasingly diverse tasks and responsibilities.
      Anthropological involvement in DVI operations is often dictated by an incident's
      specific characteristics, particularly events involving extensive fragmentation,
      commingling, or other forms of compromised remains. This paper will provide
      examples from recent DVI incidents to illustrate the operational utility of
      anthropologists in the DVI context. The points where it is most beneficial to
      integrate anthropologists into the DVI process include: (1) during recovery at
      the disaster scene; (2) at the triage station as remains are brought into the
      mortuary; and (3) in conducting the reconciliation process. Particular attention
      will be paid to quality control and quality assurance measures anthropologists
      have developed and implemented for DVI projects. Overall, this paper will explain
      how anthropological expertise can be used to increase accuracy in DVI while
      reducing the project's cost and duration.

PMID- 21877299
TI  - [Senior hospital physicians: are they able to lead?].

PMID- 21877298
TI  - Cell death in the pathogenesis of immune-mediated diseases: the role of HMGB1 and
      DAMP-PAMP complexes.
AB  - Cell death is a ubiquitous process whose immunological consequences can influence
      the course of infectious, autoimmune and inflammatory diseases. While cell death
      has long been dichotomised in terms of apoptosis and necrosis, other forms of
      death can occur and they vary in their capacity to stimulate as well as inhibit
      inflammation. The pro-inflammatory activity of dead cells results from a wide
      variety of intracellular molecules that are released as cell permeability
      increases during death. These molecules have been termed as DAMPs (damage
      associated molecular patterns) or alarmins. Among these DAMPs, HMGB1, a non
      histone nuclear protein, serves as the prototype. Although HMGB1 was originally
      thought to act alone as a cytokine, recent studies suggest that its immunological
      effects result from complexes of HMGB1 with either other DAMPs or with PAMPs
      (pathogen associated molecular patterns). Studies on the role of HMGB1 in
      pathogenesis suggest that the formation of extracellular complexes is an
      important mechanism for generating pro-inflammatory signals during cell death and
      therefore could be a potential target of new therapy.

PMID- 21877300
TI  - [Does selenium protect against cancer?].

PMID- 21877301
TI  - [Is a specific rehabilitation worthwhile in perceptual disorders?].

PMID- 21877302
TI  - [Are phosphodiesterase 4 inhibitors really helpful in COPD?].

PMID- 21877303
TI  - [Cannabinoid hyperemesis syndrome inducing acute prerenal failure and electrolyte
      disturbance].
AB  - HISTORY AND CLINICAL FINDINGS: A 36-year-old patient presented to the psychiatric
      clinic with presumed worsening of a chronic psychosis. INVESTIGATIONS: Laboratory
      values revealed acute renal failure and electrolyte imbalance. A further
      diagnostic work-up including urine analysis as well as abdominal und
      retroperitoneal sonography was normal. DIAGNOSIS, THERAPY AND CLINICAL COURSE: By
      exact history taking the clinical diagnosis of a cannabinoid hyperemesis syndrome
      (CHS) was established. Symptomatic treatment with intravenous fluids and
      electrolytes together with strict cannabis abstinence completely resolved all
      symptoms and normalized all pathologic values. CONCLUSION: Recreational use of
      cannabis is widespread. It may induce a widely unknown syndrome characterized by
      nausea, vomiting and crampy abdominal pain accompanied by frequent hot showers or
      bathing. This syndrome should be recognized as a potential cause of acute
      prerenal failure.

PMID- 21877304
TI  - [58-year-old patient with spot sign under oral anticoagulation].

PMID- 21877305
TI  - [Practical approach to hyponatremia].

PMID- 21877306
TI  - [Membranous glomerulonephritis: better therapy with autoantibody monitoring?].
AB  - Membranous nephropathy is the most common cause of nephrotic syndrome in adults.
      Binding of circulating autoantibodies to the glomerular filtration barrier leads
      to the development of this autoimmune disease. The clinical symptoms range from
      small proteinuria to severe nephrotic syndrome with enormous oedema, not
      controllable hyperlipidaemia and increased disposition for infection. One third
      of patients reach complete or partial remission of proteinuria under symptomatic
      treatment, which includes ACE-inhibitors and AT-I-blockers, loop diuretics and
      statins. Untreated the disease leads to loss of renal function over 5-10 years in
      20-30% of patients. A risk score based on proteinuria and renal function is used
      to guide the decision when to start with an immunosuppressive therapy. A better
      adapted diagnostic and therapy of membranous nephropathy may be possible through
      measurement of circulating autoantibodies directed against a podocytic
      phospholipase-A(2) receptor.

PMID- 21877307
TI  - [Natriuretic peptides in the therapy of acute decompensated heart failure].
AB  - Heart failure is the most frequent cause of hospitalization in elderly
      population. Unlike the therapy of congestive heart failure, there was only a
      modest progress in the medical treatment for acutely decompensated heart failure
      over the past several decades. Moreover, current treatment is associated with
      many limitations in clinical practice. The family of natriuretic peptides
      consists of several structurally similar polypeptides (ANP, BNP, CNP, urodilatin,
      DNP). ANP and BNP are the most characterized substances and represent an
      important compensatory mechanisms in heart failure because of their vasodilatory,
      natriuretic and antiproliferative effects. Nesiritide is a recombinant human BNP
      which has been shown to be effective in treating heart failure in several
      clinical trials. However, a recent meta-analysis revealed a nesiritide-associated
      increased 30-day-mortality rate. The results of initial small-sized trials
      suggest beneficial hemodynamic effects of urodilatin in decompensated heart
      failure. Despite of being approved for the treatment of decompensated heart
      failure in some countries, the clinical relevance of nesiritide is currently
      unclear. Urodilatin might represent a potential alternative.

PMID- 21877308
TI  - [Delivering of medical records to patients for a fee].

PMID- 21877309
TI  - [Does St. John's wort interact with finasteride?].

PMID- 21877311
TI  - A case of neonatal coxsackie B2 meningo-encephalitis in which serial magnetic
      resonance imaging findings reveal the development of lesions.
AB  - We report a patient with neonatal Coxsackie B2 meningo-encephalitis in whom
      magnetic resonance imaging (MRI) could be performed serially from the early stage
      of the disease. The patient was a 12-day-old girl born at a gestational age of 37
      weeks. She was hospitalized due to poor suckling. During her hospital stay, she
      developed clonic seizures in the right upper and lower limbs. Coxsackie B2 virus
      was detected, and a diagnosis of viral encephalitis was made. The first diffusion
      weighted images (DWI) showed an abnormal high-intensity area restricted to the
      corpus callosum and posterior limb of the internal capsule 8 h after onset of
      seizures. Repeated MRI revealed damage to the white matter, which finally changed
      into diffuse excessive necrosis followed by cystic leukomalacia. Early DWI is
      valuable for the early detection and diagnosis of neonatal meningo-encephalitis.
      This is the first report of the detailed neuroradiological course of neonatal
      Coxsackie B2 meningo-encephalitis.

PMID- 21877312
TI  - The "eye-of-the-tiger" sign may be absent in the early stages of classic
      pantothenate kinase associated neurodegeneration.
AB  - Pantothenate kinase-associated neurodegeneration (PKAN) is a rare disorder
      associated with brain iron accumulation. The brain MRI abnormality consists of T2
      hypointensity in the globus pallidus with a small hyperintensity in its medial
      part, called the "eye-of-the-tiger" sign. We report on 2 patients affected by
      PKAN, in whom MRI examination did not demonstrate the "eye-of-the-tiger" sign in
      the early stages; the typical abnormalities were detected only in the following
      examinations. Case 1 is a 4-year-old boy first studied at age 2 years for
      psychomotor delay. The brain MRI was normal. In the following 2 years, the motor
      impairment progressed. The second brain MRI at age 4 years demonstrated the "eye
      of-the-tiger" sign. Molecular analysis of the PANK2 gene revealed a missense
      mutation F228S in exon 2 in homozygosis. Case 2 is a 6-year-old boy first studied
      at age 2 years because of psychomotor delay. His brain MRI did not demonstrate
      abnormalities in the globus pallidus. In the following years spastic-dystonic
      tetraparesis became evident. A brain MRI at age 4 years demonstrated the "eye-of
      the-tiger" sign. Molecular analysis of the PANK2 gene revealed a missense
      mutation in exon 5 (N501I). Our 2 cases demonstrate that the observation of a
      normal globus pallidus in the early stage of the disease does not exclude the
      diagnosis of classic PKAN.

PMID- 21877313
TI  - [Comparison of obstructive sleep apnea in normal weighted and obese patients].
AB  - INTRODUCTION: Obesity is a well established risk factor for developing an
      obstructive sleep apnea syndrome (OSAS). However, normal weighted patients can
      suffer from OSAS, too. This study compares breathing disorders and their effect
      on sleep of normal weighted and obese OSAS patients. PATIENTS AND METHODS: The
      main sleep parameters of 32 normal weighted OSAS patients (body mass index, BMI
      <= 25 kg/m2) were compared with those of 32 obese OSAS patients (BMI >= 35 kg/m2)
      with a virtually equal apnea-hypopnea index (AHI +/- 3). RESULTS: The mean AHI in
      both groups was 27.9/h (BMI <= 25 kg/m2) and 28.0/h (BMI >= 25 kg/m2),
      respectively. Sleep efficiency, relative percentages of sleep phases S1-S4 and
      REM, mean, minimal and maximal heart rate were not significantly different in
      statistic analysis in normal weighted and obese patients. Normal weighted OSAS
      patients had a higher apnea index (11.4 vs. 6.4, p=0.040), a higher minimal
      (81.3% vs. 71.7, p=0.003) and mean (94.9% vs. 92.8%, p=0.007) oxygen saturation,
      but a smaller hypopnea index (16.5 vs. 21.6, p=0.047) and a lower index of
      snoring (175.2 vs. 394.1, p<0.001) than their obese counterparts. CONCLUSIONS: In
      OSAS patients with an equal AHI, the obese have fewer apneas, but more hypopneas,
      and a lower minimal oxygen saturation than normal weighted patients. The effect
      of OSAS on the sleep architecture, however, seems not to be associated with the
      patients' body weight.

PMID- 21877314
TI  - [Correlation between sonographic findings and level of knowledge/self-report of
      symptoms in women with uterine leiomyomata].
AB  - PURPOSE: Is there any correlation between the pre-therapeutic level of knowledge
      concerning the number/size of leiomyomata or self-reported symptoms and
      confirmation by sonography? How does the assumption of the number/size of
      leiomyomata influence the self-perception of symptoms? MATERIALS AND METHODS: In
      an anonymous questionnaire 498 patients were asked about the number, size and
      symptoms induced by leiomyomata using a visual chart from 0 - 10. The data were
      correlated with findings from transvaginal and abdominal ultrasound. RESULTS: The
      self-reported number of leiomyomata corresponded with the sonographic findings in
      80 % of patients with 1 leiomyoma and in 54 % of patients with 2 or 3
      leiomyomata, while the self-reported size only corresponded with the sonographic
      findings in 20 % to 70 % of patients. There was no correlation between the number
      of leiomymata confirmed by sonography and self-reported symptoms. There are
      significant correlations between the sonography-defined size and self-reported
      level of dysmenorrhea (p = 0.003) and self-reported pressure in the abdomen (p =
      0.02), as well as submucosal leiomyomata and hypermenorrhea (p = 0.01). Patients
      who assumed multiple or large leiomyomata >= 10 cm reported strong pressure on
      the bladder or pressure in the abdomen significantly more frequently than
      patients who assumed 1 leiomyoma (p = 0.03) or a leiomyoma less than 10 cm (p =
      0.018). CONCLUSION: There is a discrepancy between the relatively good knowledge
      about the number of leiomyomata and the lack of knowledge about their size.
      Subjective incorrect presumptions concerning the number or size of leiomymata can
      result in different disorders. Therefore, they should not be the exclusive
      indication for further operative interventions.

PMID- 21877315
TI  - [Maternal endothelial function in the course of pregnancy and postpartum -
      ultrasound-based longitudinal assessment using flow-mediated dilatation (FMD)].
AB  - PURPOSE: NO-triggered vasodilatation decreases peripheral vascular resistance in
      pregnancy. Using a noninvasive ultrasound technique, flow-mediated vasodilatation
      can be quantified. We used this technique to detect changes in endothelial
      function during pregnancy and postpartum. MATERIALS AND METHODS: In a prospective
      longitudinal study 16 healthy pregnant women were assessed for flow-mediated
      dilatation of the brachial artery during pregnancy (first trimester T 1 < 14th
      gestational week, second trimester T 2 >= 14th - 27th gestational week, third
      trimester T 3 >=  28th gestational week) and postpartum (> 6 weeks postpartum).
      As a control group, flow-mediated dilatation was determined in 19 healthy non
      pregnant women. RESULTS: Flow-mediated dilatation (%) increased significantly in
      normal human pregnancy from the first trimester (T1 8.0 +/- 5.58 vs. T 2 15.2 +/-
      5.19, p < 0.003) to the second trimester and reached its maximum in mid
      trimester. Towards the end of pregnancy, flow-mediated dilatation decreased
      significantly (T2 vs. T 3 9.15 +/- 3.61, p < 0.004). Mean values of flow-mediated
      dilatation are significantly higher during the second and third trimester of
      pregnancy compared to non-pregnant controls (T2 vs. NP 6.17 +/- 4.39, p < 0.001;
      T 3 vs. NP, p < 0.047). Postpartum flow-mediated dilatation decreased to values
      of early pregnancy. CONCLUSION: During pregnancy maternal endothelial function
      shows an increase in flow-mediated dilatation and then reverts postpartum. Using
      ultrasound-based measurement of flow-mediated dilatation, these physiological
      changes in pregnancy can be reliably detected.

PMID- 21877316
TI  - [Complex umbilical cord vein pulsations in cases with twin-twin transfusion
      syndrome: prognostic implications].
AB  - PURPOSE: Umbilical vein pulsations (UV-P) are due to various etiologies. The aim
      of the present study was to investigate the incidence and type of UV-P in
      monochorionic twins with twin-twin transfusion syndrome (TTTS). MATERIALS AND
      METHODS: TTTS cases diagnosed between 1999 and 2009 were examined
      retrospectively. The UV flow pattern taken from a free floating loop of the
      umbilical cord was classified as "non-pulsatile" (NP), "monophasic" (MP) and
      "complex" (CP). Only Doppler flow analyses prior to intervention were examined.
      RESULTS: Of 106 cases seen during the study period, 56 cases met the inclusion
      criteria. Of those, 62.5% were classified as stage III TTTS, and fetoscopic laser
      therapy was performed in 45 cases. NP flow patterns were more likely found in the
      donor twin (80.4 vs. 28.6%; p < 0.0001), while the incidence of MP (50 vs. 17.9%;
      p < 0.0006) and CP flow patterns (21.4 vs. 1.7%; p < 0.01) was higher in the
      recipient twin. Moreover, the perinatal mortality was highest in cases with CP
      (CP: 76.9 vs. MP 42.1 vs. NP: 26.2%; p < 0.01) as well as the rate of cases with
      double death. CONCLUSION: CP patterns are more frequently found in the recipient
      twin and are associated with a considerably high mortality rate. Studying the
      umbilical vein flow pattern in TTTS may provide additional information for
      counseling and prognosis similar to that obtained by expensive fetal
      echocardiography.

PMID- 21877317
TI  - Impact of maternal obesity and maternal overweight on the detection rate of fetal
      heart defects and the image quality of prenatal echocardiography.
AB  - PURPOSE: The purpose of this study was to compare the prenatal detection of four
      congenital heart defects (CHDs) and the image quality of five corresponding
      ultrasound planes among obese, overweight and normal-weight women. MATERIALS AND
      METHODS: This was a retrospective cohort study of 54,846 pregnancies undergoing
      fetal echocardiography between 18 and 37 weeks of gestation in the years from
      2000 to 2007. The women were categorized according to pre-pregnancy body mass
      index (BMI) as normal-weight (BMI < 25), overweight (BMI 25 - 29.9) and obese
      (BMI >= 30). Image quality and prenatal detection of atrioventricular septal
      defect (AVSD), double outlet right ventricle (DORV), tetralogy of fallot (TOF)
      and dextro transposition of the great arteries (D-TGA) were evaluated in the BMI
      strata. RESULTS: 108 cases with one of the considered CHDs were identified. The
      prevalence was significantly higher (relative risk = 2.04) in overweight or obese
      women (57/19,404 vs. 51/35,442, p < 0.0002) than in normal-weight women. In total
      86.1% of CHDs were correctly identified prenatally (93/108, CI: 79.6%-92.6%),
      84.3% (43/51) in the normal weight group, 88.6% (39/44) in the overweight group
      and 84.6% (11/13) in the obese group. The rate of insufficient ultrasound images
      increased from 6.4% in normal-weight patients to 17.4% in obese women within the
      108 CHD cases. CONCLUSION: The prenatal detection of fetal AVSD, DORV, TOF and D
      TGA was also satisfactory in overweight and obese patients, but image quality
      substantially decreases with an increasing maternal BMI. If there is a BMI
      associated difference in the detection rate, it probably will not exceed 20%.

PMID- 21877319
TI  - Pitfalls of ultrasonographic yolk sac measurement.
AB  - PURPOSE: Novel aneuploidy screening has been suggested for measuring the yolk sac
      during very early pregnancy. However, in a pilot study the measured diameters
      differed up to 29 % from the overall average. The aim of this study was to
      analyze the impact of image magnification on yolk sac measurement. MATERIALS AND
      METHODS: From November 3, 2009 to July 28, 2010, 119 yolk sac measurements were
      performed. During each examination, each yolk sac was examined once with standard
      image magnification and once by live scan zoom. RESULTS: The measurement values
      were 5 % smaller in the standard image. The mean relative ratio (RR), median RR,
      and standard deviation (SD) were 0.951, 0.950, and 0.103 mm, respectively (95 %
      CI 0.744 to 1.158 mm). Regarding absolute differences, the mean, median, and
      standard deviation were -0.222 mm, -0.220 mm, and 0.473 mm, respectively, (95 %
      CI -1.169 to + 0.725 mm). With standard zoom (magnified images), the SD was 1.142
      mm (1.099 mm). CONCLUSION: Five criteria should be regarded for optimal image
      settings: image magnification during live scan, optimal gain setting, enhanced
      gamma level, median section plane, and out-to-out caliper placement.

PMID- 21877318
TI  - Association of intrathoracic herniation of the liver with left heart hypoplasia
      in fetuses with a left diaphragmatic hernia but not in fetuses with a right
      diaphragmatic hernia.
AB  - PURPOSE: Predominant left heart hypoplasia is commonly observed in human fetuses
      with left diaphragmatic hernia and intrathoracic liver herniation ("liver-up").
      In contrast, marked left/right heart disproportion has not been described in
      fetuses with right diaphragmatic hernia, despite intrathoracic herniation of
      large parts of the liver. PATIENTS AND METHODS: We analyzed the data of 15
      fetuses with left diaphragmatic hernia and 10 fetuses with right diaphragmatic
      hernia and all with intrathoracic liver herniation ("liver-up") that were
      examined with fetal echocardiography between 21 weeks + 1 day and 35 weeks + 0
      days of gestation. The inflow and outflow dimensions and Z-scores of the two
      groups were statistically compared. In addition, ductus venosus streaming
      patterns were examined. RESULTS: Despite the presence of intrathoracic liver
      herniation, predominant left heart hypoplasia, defined as a mitral valve Z-score
      < - 2 in combination with a tricuspid valve Z-score that was at least 2 Z larger
      than the mitral valve Z-score in an individual fetus, was observed in 11 of the
      15 fetuses with left diaphragmatic hernia but in none of the 10 fetuses (p <
      0.001) with right diaphragmatic hernia. Preferential streaming to the right heart
      was observed in 14 of the 15 fetuses with left hernia but in none of the 7
      fetuses with right diaphragmatic hernia in whom this flow information was
      available (p < 0.0001). CONCLUSION: Intrathoracic herniation of the liver ("liver
      up") is associated with predominant left heart hypoplasia in left diaphragmatic
      hernia but not right fetal diaphragmatic hernia. Our observations indicate that
      this difference may result from different ductus venosus streaming sites in these
      conditions.

PMID- 21877320
TI  - The accuracy of BI-RADS classification of breast ultrasound as a first-line
      imaging method.
AB  - PURPOSE: The aim was to evaluate the accuracy of BI-RADS categories 3 - 5 in
      breast ultrasound (US) as the first-line imaging method. MATERIALS AND METHODS:
      5077 examinations of a consecutive, unselected and mixed collective of
      symptomatic and asymptomatic patients were performed. Of these examinations, 835
      cases of BIRADS 3 - 5 could be analyzed. RESULTS: The PPV with respect to a
      malignant lesion for BI-RADS 3, 4, 5 was 0.03, 0.48, and 0.97, respectively. When
      BI-RADS 4 and 5 cases are considered to be suspicious, the ratio of benign to
      malignant findings corresponds to 1:1.8. Analyzing BIRADS 3 - 5 lesions, the
      sensitivity, specificity and accuracy are 0.92, 0.85, and 0.87, respectively.
      CONCLUSION: The data support the feasibility of US for discriminating malignant
      from benign findings corresponding to the ACR BI-RADS classification without
      excessively increasing the number of unnecessary biopsies.

PMID- 21877321
TI  - Continuous independent quality control for fetal nuchal translucency measurements
      provided by the cumulative summation technique.
AB  - PURPOSE: The cumulative summation technique (CUSUM) is an innovative method for
      the quality control of nuchal translucency (NT) measurements. CUSUM allows
      immediate corrective intervention as soon as an unacceptable tendency is noted.
      The aim of this study was to implement an objective and dynamic quality control
      method based on the CUSUM technique for prompt analysis of fetal NT measurement
      which would be compatible with different standards in routine clinical practice.
      The findings were compared to the standard NT quality control methods currently
      in use. MATERIALS AND METHODS: Three sets of fetal NT measurements performed by
      three experienced examiners (I, II and III) were selected for retrospective
      evaluation. One additional set of NT measurements performed by examiner IV was
      prospectively assessed to approve the practicability of the method. NT
      measurements were conducted according to the recommendations of Fetal Medical
      Foundation (FMF) Germany and London. NT values were converted to Z-scores. For
      quality and accuracy evaluation, data were fed into the Digisono CUSUM software
      to create double CUSUM charts of Z-scores. In addition, histograms were composed
      from the Z-scores of each set of measurements and plotted against a normal
      Gaussian distribution. RESULTS: Three different patterns of retrospective
      performance and one set of NT measurements that was evaluated prospectively are
      presented. The full alignment of Z-scores using CUSUM curves reflected exact
      periods of under- and overestimation of NT measurements. The CUSUM chart of the
      prospective data set reveals that prompt corrective intervention of poor
      performance resulted in reconstitution of optimal results and provided sufficient
      control. In contrast, histograms of NT Z-scores only showed a minor positive or
      negative shift as compared to the expected values on the basis of Gaussian
      distribution, but could not identify poor performance. CONCLUSION: Use of the
      CUSUM technique analysing the quality of sonographic NT measurements provides the
      possibility to prospectively observe the development of the examiner's skills, to
      maintain competence and to promptly define the time when inaccurate measurements
      start to occur.

PMID- 21877322
TI  - Diagnosis of occipital meningocele at 10 weeks of gestation and its natural
      course--imaging of meningoencephalocele in early postembryonic period.

PMID- 21877323
TI  - A strategy for extending the applicability of a validated plasma calibration
      curve to quantitative measurements in multiple tissue homogenate samples: a case
      study from a rat tissue distribution study of JI-101, a triple kinase inhibitor.
AB  - A general practice in bioanalysis is that, whatever the biological matrix the
      analyte is being quantified in, the validation is performed in the same matrix as
      per regulatory guidelines. In this paper, we are presenting the applicability of
      a validated LC-MS/MS method in rat plasma for JI-101, to estimate the
      concentrations of JI-101 in various tissues that were harvested in a rat tissue
      distribution study. A simple protein precipitation technique was used to extract
      JI-101 and internal standard from the tissue homogenates. The recovery of JI-101
      in all the matrices was found to be >70%. Chromatographic separation was achieved
      using a binary gradient using mobile phase A (acetonitrile) and B (0.2% formic
      acid in water) at a flow rate of 0.30 mL/min on a Prodigy ODS column with a total
      run time of 4.0 min. The MS/MS ion transitions monitored were 466.1 -> 265 for JI
      101 and 180.1 -> 110.1 for internal standard. The linearity range was 5.02-4017
      ng/mL. The JI-101 levels were quantifiable in the various tissue samples
      harvested in this study. Therefore, the use of a previously validated JI-101
      assay in plasma circumvented the tedious process of method development/validation
      in various tissue matrices.

PMID- 21877324
TI  - Pathogenesis of postoperative adhesion formation.
AB  - BACKGROUND: Current views on the pathogenesis of adhesion formation are based on
      the 'classical concept of adhesion formation', namely that a reduction in
      peritoneal fibrinolytic activity following peritoneal trauma is of key importance
      in adhesion development. METHODS: A non-systematic literature search (1960-2010)
      was performed in PubMed to identify all original articles on the pathogenesis of
      adhesion formation. Information was sought on the role of the fibrinolytic,
      coagulatory and inflammatory systems in the disease process. RESULTS: One
      unifying concept emerged when assessing 50 years of studies in animals and humans
      on the pathogenesis of adhesion formation. Peritoneal damage inflicted by
      surgical trauma or other insults evokes an inflammatory response, thereby
      promoting procoagulatory and antifibrinolytic reactions, and a subsequent
      significant increase in fibrin formation. Importantly, peritoneal inflammatory
      status seems a crucial factor in determining the duration and extent of the
      imbalance between fibrin formation and fibrin dissolution, and therefore in the
      persistence of fibrin deposits, determining whether or not adhesions develop.
      CONCLUSION: Suppression of inflammation, manipulation of coagulation as well as
      direct augmentation of fibrinolytic activity may be promising antiadhesion
      treatment strategies.

PMID- 21877325
TI  - Validated high-performance liquid chromatographic enantioseparation of
      selenomethionine using isothiocyanate based chiral derivatizing reagents.
AB  - A high-performance liquid chromatographic (HPLC) method for enantioseparation of
      selenomethionine (SeMet) was developed using two isothiocyanate-based chiral
      derivatizing reagents [(R)-methyl benzyl isothiocyanate (MBIC) and (S)-1-(1
      naphthyl) ethyl isothiocyanate (NEIC)] and UV detection. Diastereomers of
      selenomethionine were synthesized either via stirring (using MBIC) or by
      microwave irradiation (using NEIC). Derivatization conditions were optimized and
      the synthesized diastereomers were successfully resolved using triethyl ammonium
      phosphate buffer and acetonitrile on a reversed-phase column. The method was
      validated for accuracy, precision and limit of detection. The mechanism of
      separation is also discussed.

PMID- 21877326
TI  - Determination of thyroid hormones and their metabolites in tissue using SPE UPLC
      tandem MS.
AB  - A solid-phase liquid chromatography tandem mass spectrometry (SPE LC-MS/MS)
      method was developed to determine thyroid hormones and their metabolites in
      tissue samples. The separation was achieved using reversed-phase ultra
      performance liquid chromatography (UPLC); the mass spectrometric detection was
      achieved by positive electrospray ionization and multiple reaction monitoring.
      Prior to the UPLC separation a sample cleanup with a cation exchange was
      performed. 13C6 labeled internal standards were used for the thyroid hormones and
      their metabolites. The method was linear over a range from 0.23 to 90 nmol/L for
      thyroxine and from 0.23 to 9 nmol/L for the metabolites. The lower limit of
      quantification ranged from 0.98 to 1.73 pg on column. Intra- and total assay
      variation were <10 and <15%, respectively. This method enables us to link thyroid
      hormone tissue concentrations to local iodothyronine deiodinase expressions,
      which will enhance our understanding of the regulation of thyroid hormone
      metabolism on the tissue level.

PMID- 21877327
TI  - Hungary to introduce broad range of fat taxes.

PMID- 21877328
TI  - Frontline medicine: inside Libya.

PMID- 21877329
TI  - Concerns raised over new US resident physician work hours.

PMID- 21877330
TI  - Changing perceptions of obesity--recollections of a paediatrician.

PMID- 21877331
TI  - Technophilic hubris and espionage styles during the Cold War.

PMID- 21877332
TI  - [Thorax/lung and mediastinum, pleura cancer].

PMID- 21877333
TI  - [Revised by the Japan lung cancer society: guideline for diagnosis and treatment
      of lung cancer].

PMID- 21877334
TI  - [Evaluation of efficacy for screening test of lung cancer].

PMID- 21877335
TI  - Nursing body and soul.

PMID- 21877336
TI  - Bruce D. Sidell. 20 March 1948 - 8 February 2011.

PMID- 21877337
TI  - Abstracts of the NASPSPA (North American Society for the Psychology of Sport and
      Physical Activity) 2011 Conference, June 9-11, 2011. Burlington, Vermont.

PMID- 21877338
TI  - U.S. Special Operations Command tactical trauma protocols and tactical medical
      emergency protocols for special operations advanced tactical practitioners.

PMID- 21877339
TI  - Mental Health Policy and Economics. Abstracts of the 10th Workshop on Costs and
      Assessment in Psychiatry. March 25-27, 2011. Venice, Italy.

PMID- 21877340
TI  - Abstracts of the Total Endovascular Series: Aorta II.

PMID- 21877341
TI  - Abstracts of the 39th Annual Congress of the Netherlands Society of Psychiatry,
      March 30-31, April 1, 2011, Amsterdam, The Netherlands.

PMID- 21877342
TI  - [JFR 2010. Abstracts of the French Radiology Meeting, 22-26 October 2010, Paris,
      France].

PMID- 21877343
TI  - [Abstracts of the 13th International Congress of Internal Medicine of the
      'Hospital de Clinicas'. August 24-27, 2010, Buenos Aires, Argentina].

PMID- 21877345
TI  - The movement for the promotion of competitive women's sport in Japan, 1924-35.

PMID- 21877346
TI  - The Gaelic Athletic Association and the Irish diaspora in Scotland, 1897-1947.

PMID- 21877347
TI  - The potent image and the permanent Prometheus.

PMID- 21877348
TI  - Racism, social Darwinism, anti-Semitism and aryan supremacy.

PMID- 21877349
TI  - Breeding, rearing and preparing the aryan body: creating supermen the Nazi way.

PMID- 21877350
TI  - Primacy of performance: superman not superathlete.

PMID- 21877351
TI  - Blond, strong and pure: "proto-Fascism," male bodies and political tradition.

PMID- 21877352
TI  - Icon of monumental brutality: art and the aryan man.

PMID- 21877353
TI  - "Plucky lasses," "pea soup" and politics: the role of ladies' football during the
      1921 miners' lock-out in Wigan and Leigh.

PMID- 21877354
TI  - The Birmingham four: affirmative action in South African women's sport.

PMID- 21877355
TI  - In this issue of Epigenetics: special focus on environmental epigenetics.

PMID- 21877356
TI  - Comparing dichotomous and trichotomous approaches to achievement goal theory: an
      example using motivational regulations as outcome variables.
AB  - BACKGROUND: It is commonly assumed that there is conceptual equivalence between
      the task and ego achievement goals proposed by Nicholl's (1989) dichotomous
      achievement goal theory (Nicholls, 1989), and the mastery and performance
      approach goals advanced by Elliot's (1997) trichotomous hierarchical model of
      approach and avoidance achievement motivation. AIMS: Our study examined whether
      this conceptual equivalence is reflected in measurement equivalence by examining
      the factorial structure and predictive validity of two established questionnaires
      that assess achievement goals based on Nicholl's and Elliot's approaches to
      achievement motivation. SAMPLE: Greek adolescents (N = 336, M age = 13.45 years,
      SD = 1.04). MEASURES: The participants completed the Task and Ego Orientation in
      Sport Questionnaire (Duda & Nicholls, 1992), the Approach - Avoidance Achievement
      Goals Questionnaire (Elliot & Church, 1997) and a Physical Education (PE) version
      of the Self-Regulation Questionnaire (Goudas, Biddle, & Fox, 1994). RESULTS:
      Confirmatory factor analyses of a number of competing models showed that a model
      with five correlated independent factors had the best fit. This finding suggests
      that the goals measured by the two achievement goal questionnaires are related,
      although independent constructs. However, hierarchical regression analyses
      predicting regulatory styles in PE showed quite a substantial overlap between the
      mastery and performance approach goals proposed by Elliot (1997), and the task
      and ego goals, respectively, advanced by Nicholls (1989). CONCLUSIONS: Taken
      together, our results indicate that the self-referenced and comparative1 goals of
      the TEOSQ and AAGQ are substantially related, to the extent that they have
      minimal unique predictive validity; however, they are not identical constructs.

PMID- 21877357
TI  - Marginal historiography: on Stekel's account of things.
AB  - Psychoanalytic historiography has been, and to a certain extent still is, written
      mainly from the victor's (Freud's) perspective. One of the first attempts to
      deliver an alternative account was published in 1926 by Wilhelm Stekel in a
      little-known paper entitled "On the History of the Analytical Movement," which he
      wrote in response to Freud's (1925) "An Autobiographical Study" as an attempt to
      supplement or even counter Freud's version. This paper offers a dialogical
      reading of Stekel's paper, focusing not on the question of whether or not Stekel
      was right, but on the problem of marginalization itself. What discursive
      processes contributed to the marginalization of Stekel's position, and in what
      sense could Stekel's paper be called an instance of self-marginalization?
      Analysing various intertextual links between Freud's and Stekel's accounts, the
      author finds that the two accounts were caught up in an antagonistic dialectic
      from which it was impossible to escape. Following this paper, an English
      translation of Stekel's 1926 account is presented here for the first time.

PMID- 21877358
TI  - Case law update: vicarious liability. Leal v. Secretary, Department of Health and
      Human Services, 620 F.3d 1280 (11th Cir. 2010).

PMID- 21877359
TI  - Case law update: vicarious liability. Barkes v. River Park Hospital, Inc., No.
      M2006-01214-SC-R11-CV (Tenn. October 20, 2010).

PMID- 21877360
TI  - Case law update: vicarious liability. Cenzon-DeCarlo v. Mount Sinai Hospital, 626
      F.3d 695 (2nd Cir. 2010).

PMID- 21877361
TI  - Case law update: vicarious liability. Nutter v. Kragness, 25 Mass. L. Rep. 497
      (Super. Ct. Mass. (Middlesex) 2009).

PMID- 21877362
TI  - Case law update: vicarious liability. Terrance v. Baton Rouge General Medical
      Center, 39 So. 3d 842 (Ct. App. La. 2010).

PMID- 21877363
TI  - A "creative tension": the Royal Army Medical Corps and the interplay of
      psychological and physiological in the rise of a psychoanalytic synthesis, 1915
      22.
AB  - Secondary accounts of the impact of the First World War on psychological medicine
      have traditionally painted a picture of psychoanalysis as the preserve of a small
      number of pioneering individuals, led by William Rivers and marginalized by a
      Royal Army Medical Corps (RAMC) obsessed with discipline. This view ignores the
      climate of theoretical exchange promoted by the RAMC's concern with returning as
      many soldiers to the front line as possible. The RAMC approach provided new
      resources and a positive environment for the rise of a psycho-physical
      psychoanalytic synthesis, to build on the extensive work in this field in which
      RAMC officers were engaged from a very early stage in the war. William Rivers,
      despite recent popular acclaim, stood at the rearguard of this movement, in which
      the varied and important work of William Brown is often overlooked.

PMID- 21877364
TI  - A tale of two icons: "the Jews all over the world boast of my name, pairing my
      with Einstein" (Freud, 1926).
AB  - The paper explores the relationship between Sigmund Freud and Albert Einstein,
      including the parallels in the trajectories of their scientific careers, starting
      with the 'annus mirabilis' of 1905. Noting how they shared much in common, the
      paper underlines that it was as "great Jewish thinkers" that they were most often
      twinned, and proceeds to compare and contrast the development of their self
      consciousness of being Jewish. It then traces their relationship in one meeting
      and in correspondence, both private and public, from 1926 to their deaths,
      emphasizing Freud's envy of Einstein and Einstein's ambivalent admiration of
      Freud. The paper ends with a consideration of the significance of the figure of
      Moses in both of their final years.

PMID- 21877365
TI  - Remarks on the history of the terms "object representation" and "self
      representation".
AB  - This paper reconstructs the history of the term "object representation" and "self
      representation". It seeks to show that "Objektreprasentanz" was introduced by
      Fenichel in 1926, following on from Rado, in order to be able to integrate
      identification (and the superego) into metapsychology. Freud himself never used
      "Objektreprasentanz". Fenichel's pioneering role is not discernible in the
      English literature mainly because of the diverging approaches used in the
      translation of this term (object representative versus object representation). It
      is generally acknowledged that "self representation" was first used by Hartmann
      but this paper suggests that it actually played a more crucial role in Jacobson's
      work than it did in Hartmann's. In addition, this paper sees the terms of self
      and object representation as a reflection of the paradigm change in the 1920s
      that ensued after the publication of Freud's "The Ego and the Id". In tracing the
      history of the terms, the significance of the Berlin Psychoanalytical Institute
      in the 1920s emerges as do the Berlin roots of the works written in the USA in
      the 1950s and 1960s by Edith Jacobson. She received her analytical training in
      Berlin. Fenichel was her analyst, Rado was one of her teachers, and she was
      closely involved with the work of her fellow analysts there.

PMID- 21877366
TI  - Jung and the Nazis: some implications for psychoanalysis.
AB  - The involvement of Jung with German psychotherapy in the 1930s revealed a strong
      tendency to collaborate with the Nazis, even though his behaviour was more
      contradictory than has often been acknowledged. In part this was due to anti
      Semitic sentiments; some of it was fueled by the apparent opportunity to make
      Jungian psychology dominant over its "Jewish" Freudian rival; and in part Jung's
      admiration for the energy of the Nazi movement seems to have been genuine. This
      paper traces some of the elements in Jung's activities of that period in order to
      highlight the mixture of pragmatic and ideological investments that also applied
      to many other psychotherapists, and to some German psychoanalysts at the time.

PMID- 21877367
TI  - [Guidelines for management of autosomal recessive polycystic kidney disease].

PMID- 21877368
TI  - The evolutionary turn in psychiatry: a historical overview.
AB  - Ever since Darwin, psychiatrists have been tempted to put evolutionary theory to
      use in their efforts to understand and explain various aspects of mental
      disorders. Following a number of pivotal developments in the history of
      evolutionary thought, including degeneration theory, ethology and the modern
      synthesis, this introductory paper provides an overview of the many trends and
      schools in the history of 'psychiatric Darwinism' and 'evolutionary psychiatry'.
      We conclude with an attempt to distinguish three underlying motives in asking
      evolutionary questions about mental disorders.

PMID- 21877369
TI  - Schizophrenia, evolution and the borders of biology: on Huxley et al.'s 1964
      paper in Nature.
AB  - In October 1964, Julian Huxley, Ernst Mayr, Humphrey Osmond and Abram Hoffer co
      published a controversial paper in Nature, in which they tried to explain the
      persistence of schizophrenia from an evolutionary perspective. This article will
      elucidate how the reputed authors composed this paper to make it a strong
      argument for biological psychiatry. Through a close reading of their
      correspondence, it will furthermore clarify the elements which remained unspoken
      in the paper, but which were elementary in its genesis. The first was the
      dominance of psychoanalytical theory in (American) psychiatry--a dominance which
      the authors wanted to break. The second was the ongoing discussion on the
      boundaries of biological determinism and the desirability of a new kind of
      eugenics. As such, the Huxley et al. paper can be used to study the central
      issues of psychiatry in a pivotal era of its history.

PMID- 21877370
TI  - 'This excellent observer ...': the correspondence between Charles Darwin and
      James Crichton-Browne, 1869-75.
AB  - Between May 1869 and December 1875, Charles Darwin exchanged more than 40 letters
      with James Crichton-Browne, superintendent of the West Riding Pauper Lunatic
      Asylum, Wakefield, Yorkshire. This paper charts their relationship within the
      context of Darwin's wider research networks and methods; it analyses the
      contribution that Crichton-Browne made to the writing of Expression, arguing that
      the information he provided materially affected Darwin's thesis, and that it was
      partly the need to assimilate this that led Darwin to publish Expression
      separately from Descent. The letters help to reconstruct Crichton-Browne's early
      research interests, and document Darwin's little-explored role as a patron. Both
      men are revealed within a collaborative scientific network, with each of them at
      various times a beneficiary or a promoter.

PMID- 21877371
TI  - 'Birdwatching and baby-watching': Niko and Elisabeth Tinbergen's ethological
      approach to autism.
AB  - Biographers have largely dismissed Nikolaas 'Niko' Tinbergen's late research into
      the causes and treatment of autism, describing it as a deviation from his
      previous work, influenced by his personal desires.They have pointed to the
      incoherence of Tinbergen's assertions about best practices for treating autism,
      his lack of experience with children with autism, and his apparent embracing of
      psychogenic theories that the medical research community had largely abandoned.
      While these critiques have value, it is significant that Tinbergen himself saw
      his research as a logical extension of his seminal findings in the field of
      ethology, the science of animal behaviour. The reception of his theories, both
      positive and negative, was due less to their strengths or faults than to the fact
      that Tinbergen had inserted himself into a pre-existing and acrimonious debate in
      the autism research community. Debates about the relative role of environmental
      and hereditary factors in the aetiology of autism, and the implications of both
      for the efficacy of different treatments, had political and material significance
      for the success of parent organizations' lobbying efforts and financial support
      for research programmes. Tinbergen's approach was welcomed and even championed by
      a significant minority, who saw no problem with his ideas or methods.

PMID- 21877372
TI  - The evolution of Harry Harlow: from the nature to the nurture of love.
AB  - Harlow deserves a place in the early history of evolutionary psychiatry but not,
      as he is commonly presented, because of his belief in the instinctual nature of
      the mother-infant dyad. Harlow's work on the significance of peer relationships
      led him to appreciate the evolutionary significance of separate affectional
      systems. Over time, Harlow distanced himself from the ideas of John Bowlby and
      Mary Ainsworth as well as from Konrad Lorenz's views about imprinting and
      instincts. Harlow's work did not lend support to Bowlby's belief in an innate
      need for mother love and his thesis that the mother was the child's psychic
      organizer. Nor did Harlow agree with Lorenz's view of instincts as biological,
      unmodifiable innate needs, unaffected by learning.

PMID- 21877374
TI  - Computers--they're ubiquitous!

PMID- 21877373
TI  - 'Racial differences have to be considered': Lauretta Bender, Bellevue Hospital,
      and the African American psyche, 1936-52.
AB  - This paper examines one US psychiatrist's engagement between 1936 and 1952 with a
      racialist strain of evolutionary thought. When Lauretta Bender began working with
      Bellevue Hospital's disproportionately black population, the psychiatric
      literature still circulated the crude evolutionary proposition that blacks
      remained stuck at a more primitive stage of development. In the 1930s, drawing
      insights from holistic, mechanistic and environmentalist thinking on the
      relationship between mind and body, Bender developed her own more circumspect
      racialist position. Although she largely abandoned her underdetermined version of
      racialism in the 1940s for an approach that left out race as an active factor of
      analysis, this paper contends that she probably never wrote off black primitivity
      as a theoretical possibility.

PMID- 21877375
TI  - CAD/CAM-produced surgical guides: Optimizing the treatment workflow.
AB  - The increased availability of devices for 3D radiological diagnosis allows the
      more frequent use of CAD/CAM-produced surgical guides for implant placement. The
      conventional workflow requires a complex logistic chain which is time-consuming
      and costly. In a pilot study, the workflow of directly milled surgical guides was
      evaluated. These surgical guides were designed based on the fusion of an optical
      impression and the radiological data. The clinical use showed that the surgical
      guides could be accurately placed on the residual dentition without tipping
      movements. The conventional surgical guides were used as a control for the manual
      check of the deviation of the implant axis. The direct transfer of the digital
      planning data allows the fabrication of surgical guides in an external center
      without the need of physical transport, which reduces the logistic effort and
      expense of the central fabrication of surgical guides.

PMID- 21877376
TI  - GEDAS II--new possibilities in digital contact point analysis.
AB  - The following article describes a method for the clinical depiction and
      documentation of the strength, extent, and location of occlusal contact areas on
      the basis of digitized bite records. Bite records made of low-viscosity, addition
      cured silicone in centric occlusion are digitized in a document scanner using
      incident and transmitted light scanning. Layer thicknesses < 20 microm were
      interpreted as occlusal contacts and classified as belonging to the anatomical
      structures of the occlusal surfaces. This procedure is of particular significance
      for epidemiological studies, but also of interest for dental practices and
      laboratories, since it can be used as a simple method of continuous quality
      control, documentation, and archiving of the patient's current occlusal contact
      situation.

PMID- 21877377
TI  - Do we need real-time MRI for diagnosis of temporomandibular joint disorders?
AB  - INTRODUCTION: Magnetic resonance imaging (MRI) has been approved as an
      appropriate radiological modality for temporomandibular joint (TMJ) diagnosis,
      whereas the results of international multicenter studies impressively show the
      limitations of static three-dimensional MRI. The state of the art for dynamic
      imaging of the TMJ in real-time are TrueFISP sequences in one sagittal plane. In
      order to support the diagnostics, a computer-assisted visualization procedure has
      been developed by the authors for both the static and dynamic MRI. METHODS: A
      number of validated sequences are available for the static 3D-MRI within the
      clinical routine. For dynamic MRI in real-time, True-FISP sequences in one
      sagittal plane with a slice thickness of 5-10 mm and 1.3 mm x 1.3 mm spatial
      resolution were applied. Both the dynamic and static MRI datasets are animated
      and visualized using the computer-assisted procedure. RESULTS: The computer
      assisted procedure reliably supported the clinical diagnosis, especially the
      visibility of the articular disc was enhanced. On the basis of the static MRI, a
      60-year-old patient was diagnosed with anterior disc displacement without
      reduction. In contrast, by the dynamic MRI, it was recognized how the articular
      disc was firstly somehow stretched and flattened before the mandibular condyle
      again glided under the disc, thus resulting in an anterior disc displacement with
      reduction. CONCLUSION: These results endorse the relevance of real-time diagnosis
      for the TMJ. The computer-assisted visualization has been approved as a reliable
      help for clinical diagnosis.

PMID- 21877378
TI  - Variability of closing movements, dynamic occlusion, and occlusal contact
      patterns during mastication.
AB  - Virtual articulation makes it possible to overcome the limitations of mechanical
      articulation. Novel visualization techniques have great advantages. In this
      study, the occlusal surfaces of the upper and lower teeth were digitized with a
      3D scanner, and real functional movements of the mandible were recorded using the
      Jaw Motion Analyzer (JMA), an ultrasonic measurement system. A coupling component
      designed for clinical use in the patient's mouth was utilized for precise
      referencing of the movement and scan data. Similar to a two-sided impression
      tray, the coupling tray is used to take a joint impression of the upper and lower
      arches. The JMA records the positions of the mandible and the coupling component
      in space. The virtual articulator was designed for visualization of jaw
      relationships during mastication. For analysis of intercuspation, the system
      generates dynamic images on which closing movements/ dynamic occlusion and
      contact areas are highlighted. The jaw movement data are plotted to create an
      envelope surface representing the maximum possible space occupied by the
      mandible. Such an envelope surface is a type of virtual FGP (functionally
      generated path) bite registration. It can be applied to design virtual tooth
      restorations and helps to quantify the occlusal space in a virtual environment.
      This system can be used to individually register and utilize the variability of
      occlusal function.

PMID- 21877379
TI  - Adhesive techniques and machineable high-performance polymer restorations for
      amelogenesis imperfecta in mixed dentition.
AB  - Amelogenesis imperfecta refers to a hereditary dysplasia of the enamel. As a
      result of various defects, qualitatively and/ or quantitatively abnormal enamel
      forms, while the dental structure remains normal. The following article describes
      the condition and presents the case of an 8-year-old boy who was dentally
      reconstructed both functionally and aesthetically using the adhesive technique
      and machinable high performance polymer restorations.

PMID- 21877380
TI  - Impression-free implant restorations with Cerec InLab.
AB  - The Cerec InLab software 3.80 allows for the fabrication of implant abutments and
      crowns without taking impressions. The intraoral optical impression is taken with
      the help of what is termed "scanbodies". The custom-made zirconia abutments are
      bonded to a titanium base and can thus be fastened with high torques without
      creating tensile stress.

PMID- 21877381
TI  - New online management software and DICOM viewer for dentistry.
AB  - The way we collect, store, and share dental records of our patients is rapidly
      becoming digital. Many programs have been designed to run on a single computer or
      local network to handle various tasks, so selecting a system can be complex; it
      can require high acquisition costs, update fees, and installation difficulties.
      The purpose of this article is to explain the architecture, characteristics, and
      advantages related to Web-based Management Software. In particular, this article
      describes the first Web-based Electronic Medical Record (DocSapiens.com), which
      is able to view and edit DICOM files directly online.

PMID- 21877382
TI  - Dental e-learning.

PMID- 21877383
TI  - Writing the history of psychiatry in the 20th century.
AB  - As editors of the special issue, we try to summarize here the historiographic
      trends of the field.We argue that the field of research is accommodating the
      diversity of the institutional, social and political developments. But there is
      no narrative in sight which can explain the psychiatry of the 20th century,
      comparable to the authoritative coherence achieved for the 19th century. In
      contrast, the efforts to extend these narratives to the 20th century are largely
      missing the most impressive transformation of psychiatric treatment--and self
      definition.

PMID- 21877384
TI  - 'Therapeutic community', psychiatry's reformers and antipsychiatrists:
      reconsidering changes in the field of psychiatry after World War II.
AB  - In addition to outlining some core characteristics of the therapeutic community-
      an approach developed during World War II--this article describes the
      achievements of reformist psychiatrists in the field of the therapeutic community
      during the 1950s and also discusses the appropriation of this model by the
      antipsychiatrists during the 1960s. By emphasizing the proximity of their
      respective contributions, rather than their generally accepted radical
      differences, this article is an invitation to renew the way historians consider
      the dynamics of change in psychiatry after WWII.

PMID- 21877385
TI  - Reforming psychiatric institutions in the mid-twentieth century: a framework for
      analysis.
AB  - This article develops an analytical framework of processes of institutional
      reform in psychiatry in Western countries during the last century. It discusses
      explanations of social change based on deinstitutionalization and proposes
      instead to put reform practices themselves at the centre of the analysis. Thus,
      central to this framework is the historicity of the idea of reform itself. Taking
      the case of France as an example, the article shows how the diffusion of a
      reformist ethos within psychiatry in the post-World War II period can be
      accounted for by a change in medical expertise during the first half of the
      century. It concludes with a discussion of the changing relationship between
      psychiatrists and the State in the twentieth century.

PMID- 21877386
TI  - Terra incognita: an historiographic approach to the first chlorpromazine trials
      using patient records of the Psychiatric University Clinic in Heidelberg.
AB  - Psychiatrists have often referred to the discovery of new psychopharmaceutical
      drugs in the 1950s as a 'therapeutic revolution', which allowed physicians to
      observe und measure therapeutic effectiveness easily. Contrary to this view, this
      article will argue that psychiatrists needed the patient's subjective voice to
      evaluate the effects of the drugs. In a micro-analysis of hospital records of the
      first patient to be treated with chlorpromazine in the Heidelberg clinic in 1953,
      I show the different perspectives of doctors and patients on the diagnosis and
      treatment.The analysis points up how difficult it was to get an impression of the
      drug's effectiveness.The article emphasizes the importance of the new perspective
      that includes the patient's voice in the history of psychotropic drugs after
      1945.

PMID- 21877387
TI  - Deinstitutionalizing the history of contemporary psychiatry.
AB  - While contemporary mental health services have been marked by the burgeoning of
      outpatient and preventive care, the historiography of psychiatry remains largely
      tied to the study of custodial and palliative treatment.The work in which
      contemporary psychiatry has been involved cannot be adequately understood as a
      singular, autonomous enterprise based in a residential facility. It has become a
      technoscience that operates in numerous settings and alongside multiple sciences,
      technologies and decision-makers. This paper explores what it might mean to
      'deinstitutionalize' the history of contemporary psychiatry by examining the case
      of social therapy for sex offenders in West Germany.

PMID- 21877388
TI  - 'In good times and in bad': boundary relations of psychoanalysis in post-war USA.
AB  - This paper suggests writing the history of psychoanalysis by focusing on the
      manifold ways in which its practitioners may relate to the boundaries dividing it
      from its neighbouring professions. This approach is illustrated by two loosely
      interrelated examples: the 1950s debate among leading US psychoanalysts on
      whether borderline patients can be analysed, and the 1990s responses of
      psychoanalysts to psychopharmacological treatments of schizophrenia. A close
      reading of psychoanalysts' journal publications reveals in each instance
      multiplicity (of voices), instability (of boundaries), duality (of defence and
      dialogue) and simultaneity (of internal and external addressees). At the same
      time, a common rhetorical stance emerged in each period, serving as a shared
      discursive frame while allowing a plurality of boundary relations.

PMID- 21877389
TI  - Crisis at home. How we can all make a difference.

PMID- 21877390
TI  - Families need a brighter future.

PMID- 21877391
TI  - Itching to get over it.

PMID- 21877392
TI  - A topic in 10 questions. How to support bottle feeding mothers.

PMID- 21877393
TI  - Not just a spring fever... Information and advice to help families with hay fever
      sufferers.
AB  - Hay fever is an allergy to pollen or spores presenting as an allergic
      inflammatory response in all mucous membranes of the upper airway. The UK has one
      of the highest rates (it's estimated one in four of us have hay fever) and
      symptoms are often trivialised, even though the socio-economic and health costs
      are huge. If left treated, for example, a hay fever sufferer risks developing
      asthma. Also paediatric allergists now consider the combination of eczema and hay
      fever to be a significant marker, indicating an atopic child's propensity to
      develop more serious allergic disease. Unfortunately childhood hay fever is often
      poorly treated, but a combination of sensible allergen avoidance measures and
      appropriate medication or treatments is usually sufficient to control symptoms.

PMID- 21877394
TI  - Postcards from the edge?

PMID- 21877395
TI  - What toddlers eat really matters.

PMID- 21877396
TI  - [The academies: remembering the past, programming the future].
AB  - Since the foundation of the first Academy by Plato the year 338 b.C. until now,
      Academies have gone through different periods. The first covered the centuries
      between Plato and the Renaissance. During this time, Academies were understood as
      centers for the culture of Humanities. At the beginning of the 17th Century a new
      period began, with Academies of a new style, aimed at either to the promotion of
      experimental scientific research (British model) or to the advisory of States in
      scientific questions (French model). The Spanish Academies founded in the 18th
      century followed the French model, neglecting at some extent the first goal, i.e.
      the leadership and promotion of scientific research. Looking to the future,
      Spanish Academies should increase their role as the main national centers for
      promotion and discussion of scientific research and developments.

PMID- 21877397
TI  - [Olavide and his work. The beginning of dermatology in Spain].
AB  - Jose Eugenio Olavide was the founder and promoter of Spanish dermatology, and the
      head of the first Department of Dermatology. He spread to his disciples the ideas
      of the French dermatology, especially Bazin and Hardy. He pioneered the
      application of laboratory techniques to diagnosis of skin diseases, being the
      founder of Olavide Museum, wich was of great distinction in Europe with 1500 wax
      models. This museum was open until the 60's, when it was closed and forgotten,
      being recovered in 2005 by the AEDV, wich is currently conducting its
      restoration. In the year 1872, Olavide becomes a member of the Royal Academy of
      Medicine with the speech "Parasitism or morbidly plant to reason and to facts"
      answered by Mariano Benavente. He owned the chair number 33 of this institution.

PMID- 21877398
TI  - [Adolescent sexuality].
AB  - The social Adolescent features are insecurity, narcissism, eroticism, more
      impetuosity than reason. 1/3 of adolescents have risk behaviour for health. The
      pregnancy rate in adolescent are 9/1,000 (11,720, the abort about 50 %). The
      total abort (2009) were 114,480. Increase the rate of 8,4 (1990) to 14,6/ 1,000
      (2009). The sexual education fails. The consulting about contraceptives get
      pregnancy of the OR 3,2, condom OR 2,7. The adolescent are influenced in his
      matter: oeer have 70-75 % of influence, mother 30-40 %, father 15 %, for yhe
      environment and education Cyberspace access to information: 33 % exposed to
      unwanted sexual materials, 1 in 7 solicited sexual online. The argument have 4
      central topic: Morality and Responsibility, Desire (responsibility vs
      gratification), Danger (fear related to pregnancy and STD/VIH), and
      Victimization. The prevention of STD: so called safe sex, delayed, and
      abstinence, Prevention HPV vaccine. The information is not enough, are necessary
      personal integral formation in values as self control, abstinence, mutual
      respect, responsibility, reasonable decisions.

PMID- 21877399
TI  - [Reflections about the implementation of the European higher education area in a
      school of medicine].
AB  - The autor is Dean of the School of Medicine of the Complutense University in
      Madrid. He summarizes the strategy implemented in his School in order to adapt
      the plan of teaching to the Bologna process. This strategy is related to four
      main fields: 1) Learning with patients and assessment of clinical competencies.
      2) New technologies of teaching. 3) Introduction the students to the scientific
      research. 4) Complementary education. The most relevant aspects are shown in each
      of these areas.

PMID- 21877400
TI  - [Hunger, nutrition and growth: a world overview].

PMID- 21877401
TI  - [Food production].

PMID- 21877402
TI  - [Society and the food system: a challenge of the future].

PMID- 21877403
TI  - [The sexuality by Maranon].
AB  - It is noticeable that he always had an interest in sexuality Maranon. It must be
      noted that at the time this included a series of processes that now have become
      separated from it, as all human reproduction, both from a social standpoint as a
      scientist or political issues and problems in speaking so very active. But
      specifically, referring to the current concept of sexuality, much to Maranon
      investigated because, following the ideas of Freud, then in vogue, I wanted to
      know the importance that the hormones, newly discovered, had on the brain and the
      human personality. It is quite possible to believe that there is a brain
      chemistry that modulate the individual's character, against the prevailing idea
      among psychiatrists of his time. So his research with adrenaline on the behavior
      had a huge impact. Interested in the morphological evolution of sex and sexuality
      from birth to old age, remain valid provided knowledge about the process of
      sexual maturation and decline, menopause, or rather the climacteric, as rightly
      he called that period of time. He also made a deep study and systematization of
      the pathology adel origin and evolution of sex, in which he listed as intersex,
      both anatomically and functionally and psychic. Because he was always interested
      in the relationship of human behavior, the development of your body or endocrine
      constitution and personality. This is reflected in their psychobiographies as the
      paradigm "Bioassay of Henry IV of Castile and his time".

PMID- 21877404
TI  - [Morphodifferentiation of the stapedius muscle. Personal contribution].
AB  - The aim of this study is to explain the origin of the anomalies and variations
      that affect the muscle-tendon complex of the stapes. These are interpreted from
      the model of the stapes muscle differentiation formed by two independent anlagen
      (Rodriguez-Vazquez, 2005, 2009 and Rodriguez-Vazquez et al., 2010): one for the
      belly muscle, located on the second branchial arch medially to the facial nerve;
      and another for the tendon, formed from the internal segment of interhiale. The
      external segment of the interhiale usually disappears. The pyramidal eminence is
      organized from the mesenchymal condensation sorrounding the muscle belly, which
      is independent of the second branchial arch cartilage.

PMID- 21877405
TI  - [Cell and molecular medicine in musculoskeletal system lession (sports) (healing
      cells)].
AB  - In the last years a number of different tools which will be commonly used in the
      future have merged. Among them, the use of therapeutical cells (Cell Therapy) or
      the use of bio-active molecules after the identification of the molecular basis
      of a given pathology (Molecular Medicine), are two approaches. Currently, the
      autologous chondrocyte implantation to treat the articular cartilage lesions is
      considered as a consolidated therapy.

PMID- 21877406
TI  - [Thermal stress].
AB  - Among the many negative effects that the heat "in the body can cause heat stroke
      emphasizes" the characteristics and pathogenesis are described. It is complete
      with the literature study will result in a monograph.

PMID- 21877407
TI  - [Chemical causes of Parkinson's disease].
AB  - It is a critical study of scientific methodology best suited to the etiology of
      Parkinson's disease, essential basis for its prevention, with an overview of the
      main factors incriminated between environmental highlighting the effect of
      neurotoxins, hoping to complete the health aspects this important disease in an
      essay in which he attends the literature.

PMID- 21877408
TI  - [Catalonian surgery in the twentieh century].
AB  - In order to round it off, I would like to say that the development of surgery
      during these last hundred years has been quicker than throughout the history of
      mankind. And, as far as the Catalonian Health Service is concerned, it must be
      said that its doctors have played an extremely important role not only in the
      general practice of medicine and surgery but also in all specialization. Surgeons
      here have followed the French school passionately and have widened their
      knowledge by going deeply into Central European sources. All these hospitals I
      have mentined have been, are and will be the pride of those who consider being a
      doctor an "art". They are there to offer what society demands as the most coveted
      asset: health. Please, allow me to dedicate this speech to those from whom we
      learned not only the theory and practice of medicine but also the ethics,
      aesthetics and art of life.

PMID- 21877409
TI  - [The neurotransmision from the other side].
AB  - The discovery of how neurons communicate, like the cracking of genetic code and
      the creation of the atomic bomb is one of the fundamental scientific development
      of the twentieth century. In this paper we described the history of scientific
      discovery of neurohumoral transmission against the backdrop of the two torld and
      the fascinating lives of several scientists whose work was affected by the social
      and political events in their time. The lives and history of the main
      protagonists Sir Henry Dale, Otto Loewi and Walter Cannon are reported here. Otto
      Lewi and William Felberg--as jews--were arrested by nazi troops and Otto Krayer-
      not a jew--for not accepting one universitary offer of nazu party. All of them,
      and many others, were compelled to migrate from Germany to Great Britain, where
      Sir Henry Dale helped them to continue their work and their lives. All this
      scientist played an important role in the work on chemical neurotransmission
      which finally cristalized in awarding the Nobel. Price--in 1936--to Otto Loewi
      and Sir Henry Dale, but not to Walter Cannon, in this case, for adopting a
      controversial theory. The role of Rockefeller Foundation in this history is also
      comtemplated.

PMID- 21877410
TI  - [Cell therapy with chondrocytes. Evaluation of cell viability in cultures].
AB  - Autologous chondrocyte implantation is an established method for the treatment of
      chondral defects. However there is insufficient evidence to say whether cell 
      based therapy is superior to other treatment strategies in articular cartilage
      lesions. In this work we have determined cell viability of animal and human
      condrocytes in several passages to identify the specific cell passage that is
      more appropiate to be used in tissue engineering. We compare the results using
      tripan blue, X-Ray electron probe microanalysis and microarrays. When tripan blue
      is used a high viability--more than 80 %--was observed in all passeges. When it
      was used X-Ray microanalysis the K/ Na index only showed high viability in some
      subcultures. Whereas only cell death with ruptured cell membrane are stained with
      tripan blue, X-ray microanalysis determination detecs cell death before the
      rupture of the membrane. The gene expression for caspase and chondral
      differentiation confirm the heterogeneity in cell viability for different cell
      passages and therefore the possible influence of cell viability in the
      effectiveness of autologous chondrocyte implantation.

PMID- 21877411
TI  - [Organic injuries in doped elite sports men].
AB  - The technical level of the sportsmen in different Sports increases every year.
      The athletic records reach new heights and the margin between success and failure
      in the world of sports becomes smaller. Therefore, trainers and sportsmen look
      for this small difference to secure the victory. They may try to get the support
      from ergogenetic substances (to improve the performance). Some of these supports
      may benefit the performance but others may have lethal consequences. The author
      presents the consequences in human body of the elite sportsman who have used
      prohibited substances to improve the sport performance.

PMID- 21877412
TI  - [REM sleep modulation by non-GABAergic neurons of the hypothalamus and basal
      forebrain].
AB  - The ventral part of the oral pontine reticular nucleus (vRPO) is a demonstrated
      site of brainstem REM-sleep generation and maintenance. The vRPO has reciprocal
      connections with structures that control other states of the sleep-wakefulness
      cycle, many situated in the basal forebrain and the diencephalon. The aim of the
      present revision is to map, using the results described in previous publications
      of our group, the local origin of the basal forebrain and hypothalamus non
      GABAergic projections to the vRPO, and specially the contribution of the
      hypothalamic neurons positive to hypocretin/orexin (H/O) peptides. I summarize
      non-GABAergic projections to the vRPO from the: ipsilateral central amygdaline
      nucleus and the stria terminalis bed nuclei, bilateral projections, but most
      abundant in the ipsilateral side, from the median preoptic nucleus, medial and
      lateral preoptic areas, abundant from the zona incerta and dorsal, lateral,
      posterior and perifornical hypothalamic areas. Very abundant bilateral
      projections of H/O neurons to the vRPO are described, expressive of the important
      modulation exerted by these neurons on the vRPO nucleus. I discuss the functional
      significance of the above results and the corresponding mechanisms, supported by
      physiological and ultrastructural results of our group. Based on the connections
      and action mechanisms of H/O neurons on the vRPO, which produce the decreased
      activity of neurons in this nucleus and, therefore, inhibition of REM sleep, I
      reflect briefly on narcolepsy pathophysiology.

PMID- 21877413
TI  - [Neuroanatomic bases of hypocretin actions on the ascending reticular activating
      system: a contribution to narcolepsy physiopathology].
AB  - The present study describes at the ultrastructural level the hypocretinergic
      innervation of brainstem reticular formation neurons that project to the medial
      frontal cortex in the rat. In addition, we assess, by using dual
      immunofluorescence techniques, the proportion of those reticular neurons
      containing specific neurotransmitters. Our results indicate that hypocretinergic
      axons make asymmetric synapses with neurons within the locus coeruleus, ventral
      tegmental area, dorsal raphe nucleus and laterodorsal tegmental nucleus that
      target the medial frontal cortex, Hypocretins could facilitate wakefulness and
      cortical activation, therefore, by activation of those neurons with cortical
      projections in these four reticular nuclei.

PMID- 21877414
TI  - [The environment of the first stage of the Academia Medica Matritense (2.0 third
      of the 18th century): determinant notes for a suitable valuation].
AB  - The intrinsic nature of the written histories of the Real Academia Nacional de
      Medicina until the present is confirmed and the construction of a contextualized
      history of its first stage and in relation to the proliferation of contemporary
      health-related academies of pharmacists, surgeons and doctors is started.

PMID- 21877415
TI  - [Total arthroplasty: the other surfaces; wear and tear and osteolysis].
AB  - Total replacement remains a successful solution for degenerative, inflammatory
      and postraumatic diseases in large joints. This treatment has considerably
      improved the quality of life of the patients. Despite recent innovations in
      biomaterials, implant design and surgical technique, there are still failures,
      most of them related to wear at the surface of some component. Particles are
      generated that produce inflammatoty and osteolytic reactions leading to implant
      loosening. In that case, revision surgery is mandatory to remove and substitute
      the worn component. The operation is far more difficult and costly, has a higher
      rate of complications and a worse outcome that the initial surgery. This general
      review of the problem is focused on the specific features of wear particles and
      the cellular and molecular mechanisms of the biological reactions in the
      osteoclastic and osteoblastic pathways. Osteolysis is described as a pathological
      modification of normal bone remodeling with the interaction between osteoblasts
      and osteoclasts as the main feature. We include some contributions of our
      laboratory at H U La Paz. Having reached an advanced identification of the
      molecular factors involved in wear osteolysis, many research groups are trying to
      develop potential "biologic" (non surgical) therapies for the prevention and
      treatment of bone loss.

PMID- 21877417
TI  - Care of the insane in Lubeck during the 17th and 18th centuries.
AB  - Only selected aspects of the history of the House of the Poor Insane in the
      Hanseatic Free City of Lubeck have been studied to date.This article presents the
      results of an entire source study of this small institution in the 17th and 18th
      centuries, and briefly also during the next 40 years after the opening of a new
      building. In addition to the minute-book of the Governors, now kept in the Lubeck
      Municipal Archives, the results are based primarily on the account-books,which
      illustrate the institution's social history and activities. Examples are given.
      During most of the 17th century, the House was generally rather like a prison for
      the insane, but at the end of this century and in the early 18th there was a
      reform phase.This was followed by phases of repression and 'containment' at the
      end of the 18th century and in the early 19th century, before a renewed reform by
      the medical profession.The findings for Lubeck are compared with the development
      of inpatient care in institutions elsewhere, and the decisive factors in Lubeck
      are discussed.

PMID- 21877416
TI  - Role of neprilysin in airway inflammation induced by diesel exhaust emissions.
AB  - In this study, we examined the role of neprilysin (NEP), a key membrane-bound
      endopeptidase, in the inflammatory response induced by diesel exhaust emissions
      (DEE) in the airways through a number of approaches: in vitro, animal, and
      controlled human exposure. Our specific aims were (1) to examine the role of NEP
      in inflammatory injury induced by diesel exhaust particles (DEP) using Nep-intact
      (wild-type) and Nep-null mice; (2) to examine which components of DEP are
      associated with NEP downregulation in vitro; (3) to determine the molecular
      impact of DEP exposure and decreased NEP expression on airway epithelial cells'
      gene expression in vitro, using a combination of RNA interference (RNAi) and
      microarray approaches; and (4) to evaluate the effects on NEP activity of human
      exposure to DEE. We report four main results: First, we found that exposure of
      normal mice to DEP consisting of standard reference material (SRM) 2975 via
      intratracheal installation can downregulate NEP expression in a concentration
      dependent manner. The changes were accompanied by increases in the number of
      macrophages and epithelial cells, as well as proinflammatory cytokines, examined
      in bronchoalveolar lavage (BAL) fluid and cells. Nep-null mice displayed
      increased and/or additional inflammatory responses when compared with wild-type
      mice, especially in response to exposure to the higher dose of DEP that we used.
      These in vivo findings suggest that loss of NEP in mice could cause increased
      susceptibility to injury or exacerbate inflammatory responses after DEP exposure
      via release of specific cytokines from the lungs. Second, we found evidence,
      using in vitro studies, that downregulation of NEP by DEP in cultured human
      epithelial BEAS-2B cells was mostly attributable to DEP-adsorbed organic
      compounds, whereas the carbonaceous core and transition metal components of DEP
      had little or no effect on NEP messenger RNA (mRNA) expression. This NEP
      downregulation was not a specific response to DEP or its contents because the
      change also occurred after exposure to urban dust (SRM 1649a), which differs in
      physical and chemical composition from DEP. Third, we also collected the
      transcriptome profiles of the concentration-effects of SRM 2975 in cultured BEAS
      2B cells through a 2 X 3 factorial design. DEP exposure upregulated 151 genes and
      downregulated 59 genes. Cells with decreased NEP expression (accomplished by
      transfecting an NEP-specific small interfering RNA [siRNA]) substantially altered
      the expression of genes (upregulating 17 and downregulating 14) associated with
      DNA/protein binding, calcium channel activities, and the cascade of intracellular
      signaling by cytokines. Data generated from the combined RNAi and microarray
      approaches revealed that there is a complex molecular cascade mediated by NEP in
      different subcellular compartments, possibly influencing the inflammatory
      response. Fourth, in a controlled human exposure study, we observed significant
      increases in soluble NEP in sputum after acute exposure to DEE, with an average
      net increase of 31%. We speculate that the change in NEP activity in sputum, if
      confirmed in larger epidemiologic investigations at ambient exposure levels to
      DEE, may provide a useful endpoint and promote insight into the mechanism of DEE
      induced airway alterations.

PMID- 21877418
TI  - From stack-firing to pyromania: medico-legal concepts of insane arson in British,
      US and European contexts, c. 1800-1913. Part 2 .
AB  - The second part of this paper explores deepening doubts about pyromania as a
      special insanity, British debates post-1890, and pyromania's supplanting with the
      broader diagnostic category of insane incendiarism. It assesses the conceptual
      importance of revenge and morbid-motivations for arson, and the relationship of
      Victorian and Edwardian concepts of arson to more modern psychiatric research.The
      main objective is to ascertain the extent to which Victorian and Edwardian medico
      psychologists and medical legists arrived at meaningful and workable definitions
      of criminal insanity linked to arson. It concludes by emphasizing the
      limitations, contentiousness and inconsistencies in the use of technical terms
      such as'pyromania', contrasted with the qualified success of authorities in
      arriving at more viable and broadly acceptable explanations of insane
      firesetting.

PMID- 21877419
TI  - Forgotten paths: culture and ethnicity in Catalan mental health policies (1900
      39).
AB  - Between 1900 and 1939 the regional government in Catalonia discussed a complete
      reform of the psychiatric institutions inherited from the nineteenth century. The
      debate was centred on the Spanish government's lack of interest in mental health
      policies and the growing demand for services. The projects developed between 1900
      and 1939 opened a wide-ranging discussion on the role of ethnic and cultural
      factors in shaping mental illness, and the need to adapt the new facilities to
      the ethnic features of Catalonia. This study explores the production of Catalan
      psychiatric discourses and their ideological roots, and the development of public
      policies up to the end of the Spanish Civil War (1936-39). The paper concludes
      with a discussion of the influence of pre-war Catalan mental health policies on
      the wartime practice of psychiatry and, later, on the development of the French
      psychotherapie institutionnelle after World War II.

PMID- 21877420
TI  - 'War neurosis' during the Spanish Civil War (1936-39).
AB  - The aim of this contribution is to analyse the incidence and treatment of war
      neurosis in Madrid during the Spanish Civil War. First, the scientific papers
      published on war neurosis during and after the war are examined. Then the work of
      Gregorio Bermann (1894-1972), a member of the International Brigades who
      organized the frontline Neuropsychiatric Service at the Hospital de Chamartin de
      La Rosa (Madrid), is analysed. Las neurosis en la guerra, published in 1941,
      which recounts Bermann's personal experience in the care of war neurosis in
      Spain, is also discussed.

PMID- 21877421
TI  - Diagnostic politics: the curious case of Kanner's syndrome.
AB  - The consensus US (not European) narrative regarding diagnosis and aetiology of
      autism posits that misguided 'parent-blaming' psychogenic causes were supplanted
      due to solid research proving the presence of organic causes.Yet, upon scrutiny,
      it is questionable that the high-functioning, often high-IQ minority--about 15%
      of those labelled autistic--whose condition Kanner in 1943 first dubbed
      'infantile autism' were absorbed into the 'autistic spectrum' on the basis of
      scientific evidence. Extra-scientific factors must be addressed in order to
      understand the status of the category today.

PMID- 21877422
TI  - One hundred years after Sigmund Freud's lectures in America: towards an
      integration of psychoanalytic theories and techniques within psychiatry.
AB  - The impact of Sigmund Freud's lectures in America in 1909 is discussed. Some of
      the roots of psychoanalysis and their contemporary relevance are addressed:
      neurological ideas, the discussions of the sexologists, and the degeneration
      theories at the turn of the twentieth century. Factors which led to the dominance
      of psychoanalysis in psychiatry included, in particular, its arguments against
      the hopelessness of degeneracy theories;yet,by isolating itself from mainstream
      academic psychiatry and psychology,organized psychoanalysis itself contributed to
      its own subsequent marginalization. In order to re-integrate itself with
      mainstream psychiatry, psychoanalysis needs to appreciate the importance of
      systematic demonstrations of the therapeutic power of
      psychodynamic/psychoanalytic concepts and techniques when caring for individuals.

PMID- 21877423
TI  - Malaria fever therapy for general paralysis of the insane in Denmark.
AB  - This article explores the history of general paralysis and malaria fever therapy
      in Denmark. I argue that the small size of the country gave Danish psychiatrists
      excellent opportunities for performing statistical studies of general paralysis
      in the 19th century. In the early 1920s malaria fever therapy was introduced in
      Danish mental hospitals and raised hopes of a cure for paralytics. Malaria fever
      therapy became popular among Danish psychiatrists, but the new therapy also
      raised ethical questions and led to the first regulations concerning informed
      consent in the history of Danish psychiatry.

PMID- 21877424
TI  - Giving back to the community: working as a temporary program director at the
      National Science Foundation.

PMID- 21877425
TI  - Mentoring as a player coach.

PMID- 21877426
TI  - Research advisor's checklist.

PMID- 21877427
TI  - King George III and porphyria: a clinical re-examination of the historical
      evidence.
AB  - The diagnosis that George III suffered from acute porphyria has gained widespread
      acceptance,but re-examination of the evidence suggests it is unlikely that he had
      porphyria.The porphyria diagnosis was advanced by Ida Macalpine and Richard
      Hunter, whose clinical symptomatology and historical methodology were flawed.They
      highlighted selected symptoms, while ignoring, dismissing or suppressing counter
      evidence.Their claims about peripheral neuropathy, cataracts, vocal hoarseness
      and abdominal pains are re-evaluated; and it is also demonstrated that evidence
      of discoloured urine is exceedingly weak. Macalpine and Hunter believed that
      mental illnesses were primarily caused by physical diseases, and their diagnosis
      of George III formed part of a wider agenda to promote controversial views about
      past, contemporary and future methods in psychiatry.

PMID- 21877428
TI  - The madness of King George III: a psychiatric re-assessment.
AB  - This research, based on a study of King George III's medical records and of
      contemporary diaries of his courtiers and equerries, further confirms the
      considerable doubt on the claim of Richard Hunter and Ida Macalpine that the King
      suffered from recurrent attacks of acute porphyria.The present study examines the
      above records from a psychiatric viewpoint, together with some additional
      reports, to re-assess the nature of the King's maladies. It concludes that he
      suffered from recurrent mania (four episodes), with chronic mania and possibly a
      degree of fatuity during the last decade of his life.This is in agreement with
      previous reports that he suffered from manic-depressive psychosis.

PMID- 21877429
TI  - Science and morals in the affective psychopathology of Philippe Pinel.
AB  - Building on what he believed was a new 'medico-philosophical' method, Philippe
      Pinel made a bold theoretical attempt to find a place for the passions and other
      affective posits in psychopathology. However, his courageous attempt to steer
      affectivity onto the high seas of medical science ran aground on two great reefs
      that still threaten the scientific status of affectivity today.
      Epistemologically, there is the elusive nature of the signs and symptoms of
      affectivity. Ethically, there is the stubborn manner in which fact and value are
      intermingled in affectivity. Both obstacles posed insuperable difficulties for
      Pinel, who never really managed to extricate his affective psychopathology from
      the confines of the Lockean intellectual paradigm.

PMID- 21877430
TI  - Wimmer's concept of psychogenic psychosis revisited.
AB  - In the early twentieth century the Danish psychiatrist August Wimmer (1872-1937)
      developed the concept of psychogenic psychosis (PP) as a category of mental
      disorders separate from schizophrenia and manic depression. It subsumed a variety
      of clinical conditions with affective, confusional and paranoid features
      typically triggered by a psychical trauma.Wimmer's work has established itself as
      one of the classic texts in Scandinavian psychiatry but, for linguistic reasons,
      long remained almost unknown in other European countries.Translated into English
      in 2003, it is now available for historical and psychopathological analyses. This
      paper describes the original meaning of PP and sets it in context, then discusses
      the implications arising from the usage of the diagnostic categories introduced
      to replace PP in modern international classifications.

PMID- 21877431
TI  - J.-M. G. Itard's 1825 study: movement and the science of the human mind.
AB  - Jean-Marc Gaspard Itard's 1825'Study of several involuntary functions of the
      apparatus of movement,gripping, and voice' discusses 10 individuals with
      uncontrolled movements but no other significant impairments.Thus, otherwise
      normal people move in inappropriate ways against their better judgement. Although
      the study contains the first clinical description of Tourette Syndrome, it has
      received little attention beyond that notice. Examined in its entirety and in its
      cultural context, Itard's study characterizes patients' movements in terms of the
      will, propriety, animals and gender. Lacking control over their movements, the
      individuals are underdeveloped humans. Accordingly, sufferers' facial expression,
      bodily movements and unplanned vocalizations render them more animal than human
      and more deviant than normal, although they are neither insane nor evil.

PMID- 21877432
TI  - Hallaran's circulating swing.
AB  - William Saunders Hallaran (c.1765-1825) was physician superintendent at the
      County and City of Cork Lunatic Asylum for 40 years, where he distinguished
      between mental insanity and organic (systemic) delirium. In treatment he used
      emetics and purgatives, digitalis and opium, the shower bath and exercise, and
      argued that patients should be saved from 'unavoidable sloth' by mental as well
      as manual occupation. However, it is as an exponent of the circulating swing,
      proposed by Erasmus Darwin and used by Joseph Cox, that he is remembered. His
      best results were achieved, as he recorded in An Enquiry in 1810, by inducing
      sleep in mania of recent onset, but perhaps his most enduring observation was
      that some of his patients enjoyed the rotatory experience, and he had enough
      sense to allow the use of the swing as a mode of amusement.

PMID- 21877433
TI  - The work of John Hughlings Jackson: part I by JM Lopez Pinero. 1973.
AB  - After returning to Spain from a research period in London on a Wellcome Trust
      scholarship, Jose Maria Lopez Pinero published in 1973 a short book entitled John
      Hughlings Jackson (1835-1911), Evolucionismo y Neurologia (Madrid, Editorial
      Moneda). Written from the perspective of the classical German medical
      historiography that the author had imbibed from Werner Leibbrand and Annemarie
      Wettley, this work truly added to Jacksonian scholarship. Neither hagiographic
      nor nitpicking, it offered a sober assessment of the contribution of the great
      Yorkshireman and it was soon to become a minor classic among connoisseurs.
      Although important additions to Jacksonian scholarship have appeared since 1973,
      Lopez Pinero's book has retained its relevance. It will be published in History
      of Psychiatry in two parts.

PMID- 21877434
TI  - Psychiatry in colonial Australia: mad women and their attendants in Victoria's
      asylums, 1848-88.

PMID- 21877435
TI  - Cancer center design must focus on patient needs.

PMID- 21877436
TI  - Cancer center design: enhancing the patient care environment.

PMID- 21877437
TI  - How do you overcome obstacles in your oncology practice's design?

PMID- 21877438
TI  - Developing an outpatient symptom management clinic.

PMID- 21877439
TI  - How do you think the patient care environment affects outcomes?

PMID- 21877440
TI  - The case of anticipated alopecia.

PMID- 21877442
TI  - Almost anyone can write for publication.

PMID- 21877441
TI  - Treating breast cancer in developing countries.

PMID- 21877443
TI  - Networking puts you in the know.

PMID- 21877444
TI  - Precision of repeated, Doppler-derived indirect blood pressure measurements in
      conscious psittacine birds.
AB  - Although the use of indirect methods for measuring blood pressure has become
      commonplace in dogs and cats, it is uncertain whether these methods can be
      extended to avian species with any proven accuracy or precision. To evaluate the
      precision of indirect blood pressure measurement in conscious psittacine birds by
      the Doppler flow method, 25 psittacine birds, weighing between 230 and 1263 g and
      representing 17 commonly kept species, were examined. Birds were manually
      restrained, and indirect blood pressure measurements were obtained by placing a
      cuff around the limb proximal to a Doppler ultrasonic flow detector held over
      either the basilic or cranial tibial artery. Three sets of 3 measurements were
      obtained from each wing and leg site, with cuff size and site based on pilot
      study data identifying the selection criteria of cuff placement with the least
      variance among repeated measurements. A mixed-effects linear regression analysis
      was performed to evaluate the differences among mean blood pressure measurements
      in the individual bird, obtained from the wing versus leg site as well as from 3
      different cuff placements at each site. Results showed variation attributable to
      the limb was not significant. However, blood pressure measurements varied
      significantly between cuff placements on the same limb from the same bird and
      among individual birds. The precision of these indirect blood pressure
      measurements was poor. From these results, the meaning and value of Doppler
      derived indirect blood pressure measurements obtained in psittacine birds remains
      in question, warranting further research.

PMID- 21877445
TI  - Plasma osmolality reference values in African grey parrots (Psittacus erithacus
      erithacus), Hispaniolan Amazon parrots (Amazona ventralis), and red-fronted
      macaws (Ara rubrogenys).
AB  - Birds are routinely presented to veterinarians for dehydration. Success with
      these cases ultimately depends on providing replacement fluids and re
      establishing fluid homeostasis. Few studies have been done to determine reference
      ranges for plasma osmolality in birds. The goals of this study were to determine
      reference values for plasma osmolality in 3 species of parrots and to provide
      recommendations on fluid selection for replacement therapy in these species.
      Blood samples were collected from 21 adult Hispaniolan Amazon parrots (Amazona
      ventralis), 21 Congo African grey parrots (Psittacus erithacus erithacus), and 9
      red-fronted macaws (Ara rubrogenys), and were placed into lithium heparin
      containers. Plasma osmolality was measured in duplicate with a freezing point
      depression osmometer. Summary statistics were computed from the average values.
      Reference ranges, calculated by using the robust method, were 288-324, 308-345,
      and 223-369 mOsm/kg in African grey parrots, Hispaniolan Amazon parrots, and red
      fronted macaws, respectively. The mean +/- SD values were 306 +/- 7, 327 +/- 7,
      and 304 +/- 18 mOsm/kg in African grey parrots, Hispaniolan Amazon parrots, and
      red-fronted macaws, respectively. Comparisons with osmolality values in mammals
      and values previously reported for psittacine bird species suggest that plasma
      osmolality is slightly higher in parrots than in mammals, species-specific
      differences exist, and differences between reported values occur. Overall, fluids
      with an osmolarity close to 300-320 mOsm/L, such as Normosol-R, Plasmalyte-R,
      Plasmalyte-A, and NaCl 0.9%, can be recommended in parrots for fluid replacement
      therapy when isotonic fluids are required.

PMID- 21877446
TI  - Serum biochemical values of adult ostriches (Struthio camelus) anesthetized with
      xylazine, ketamine, and isoflurane.
AB  - Because of the size, speed, and powerful kicking ability of adult ostriches
      (Struthio camelus), chemical immobilization and general anesthesia are commonly
      used in these animals to provide veterinary care. To determine the serum
      biochemical values in ostriches anesthetized with xylazine and ketamine and
      isoflurane, 7 healthy adult ostriches (weighing 100 to 130 kg) were fasted for 12
      hours. Each bird received an intramuscular injection of xylazine (4 mg/kg),
      followed 20 minutes later by an intravenous injection of ketamine (8 mg/kg), and
      were then intubated and maintained under anesthesia with isoflurane gas. Jugular
      blood samples were collected from each bird immediately before, and 20 minutes
      after, administration of xylazine; 10 and 20 minutes after the administration of
      ketamine; 10, 30, and 50 minutes after the delivery of isoflurane; and 20 and 50
      minutes after discontinuing isoflurane. Concentrations of potassium and glucose
      increased significantly after the administration of ketamine, and that increase
      was maintained until the end of the study period. During recovery, levels of
      creatinine and amylase increased significantly. We conclude that administration
      of xylazine and ketamine and isoflurane anesthesia may affect the concentration
      of some serum biochemical values. These results should be taken into account when
      blood samples are evaluated in chemically immobilized or anesthetized ostriches.

PMID- 21877447
TI  - Differences in protein fractions of avian plasma among three commercial
      electrophoresis systems.
AB  - Previous studies have defined the presence of 6 protein fractions in plasma from
      many psittaciform species. Additionally, extensive reference intervals have been
      published for many of these species with the Beckman Paragon electrophoresis
      system, which had been commonly used in clinical laboratories to analyze the
      protein fractions of avian plasma. In mid-2009, Beckman discontinued the Paragon
      product line, leaving 2 primary alternative systems: Helena and Sebia. To compare
      electrophoresis results from the 3 commercial protein electrophoresis systems,
      specimens from 40 African grey parrots (Psittacus erithacus) were analyzed with
      the electrophoresis systems from Beckman, Helena, and Sebia. Marked differences
      in fraction migration were found between the Beckman/Helena and Sebia systems,
      which manifested as a large decrease in prealbumin and an increase in alpha1
      globulins in the latter system. Both proportional and constant errors were
      observed among the fraction quantitation data of both the Helena and Sebia
      systems compared with the Beckman system. Based on Bland-Altman plot data and
      imprecision studies, the Helena system appears more similar with the Beckman
      system, although neither the Helena nor the Sebia systems are identical to the
      Beckman system. Because of the differences in electrophoresis methods, clinicians
      should be careful to consistently use particular clinical laboratories. For best
      application, reference intervals should be established based on both species and
      electrophoresis system.

PMID- 21877448
TI  - Surveys of avian practitioners and pet owners regarding common behavior problems
      in psittacine birds.
AB  - Avian veterinarians and pet bird owners were solicited to participate in online
      surveys to gather information about behavior problems in pet birds. A total of 84
      avian veterinarians' and 203 psittacine bird owners' responses were analyzed.
      Behaviors with a high prevalence and a high level of owner concern, in descending
      order, were aggression, screaming, and feather picking. Veterinarians reported
      that the most common behavior problems presented to them were feather picking,
      chronic egg laying, aggression, and screaming, in that order. Most owners seeking
      advice went elsewhere before talking to their veterinarian. When consulted, most
      veterinarians recommended a combination of a medical workup, nutritional changes,
      housing changes, and environmental enrichments for these problem behaviors.
      Because owners do not often seek a veterinarian's advice, behavior problems exist
      in birds that are not being addressed by veterinarians. Advising veterinarians to
      question owners about problem behaviors at every visit will facilitate discussion
      and improve the treatment and welfare of pet psittacine birds.

PMID- 21877449
TI  - Use of a locking compression plate as an external fixator for repair of a
      tarsometatarsal fracture in a bald eagle (Haliaeetus leucocephalus).
AB  - We describe the successful treatment of a tarsometatarsal fracture in a mature
      bald eagle (Haliaeetus leucocephalus) using a locking compression plate as an
      external fixator. The anatomy of the area (inelastic dermis and minimal
      subcutaneous space) and the high forces placed on a fracture at that site
      necessitated a unique approach to fixation. The unconventional use of a locking
      compression plate as an external fixator was minimally invasive, well tolerated
      by the eagle, and provided adequate stability in opposing fracture forces. This
      technique may serve as a method of fixation for tarsometatarsal fractures in
      other large avian species.

PMID- 21877450
TI  - Bilateral seminoma with hepatic metastasis in a cockatiel (Nymphicus
      hollandicus).
AB  - Abstract: An 18-year-old, intact male cockatiel (Nymphicus hollandicus) presented
      with a clinical history of dyspnea, lethargy, and reluctance to perch. Coelomic
      ultrasonographic examination revealed hypoechoic nodules in the proximity of, and
      within, the liver. The bird did not respond to supportive care and was
      euthanatized. At necropsy, the testes were bilaterally enlarged, whitish-tan,
      firm, and multilobulated. The right hepatic lobe contained a mass that had a
      similar color and consistency to those in the testes. On histologic and
      ultrastructural examinations, the diagnosis was bilateral testicular seminoma
      with hepatic metastasis. To our knowledge, this is the first case of a metastatic
      bilateral testicular seminoma reported in a cockatiel.

PMID- 21877451
TI  - Bispectral index reveals death-feigning behavior in a red kite (Milvus milvus).
AB  - Red kites (Milvus milvus) are birds of prey known to feign death in the presence
      of humans. An adult wild red kite was anesthetized with isoflurane for
      coelioscopy. During surgery, heart rate and respiratory rate ranged from 240 to
      260 beats per minute and from 16 to 28 breaths rates per minute, respectively.
      Pupil and corneal reflexes remained present, and body temperature was maintained
      at 40.4 degrees C (104.7 degrees F). Suppression ratio was 0 during the
      anesthetic episode. The bispectral index was 44 immediately after intubation,
      ranged from 44 to 57 during maintenance of anesthesia, and was 59 at the moment
      of extubation. The index increased to 85 while the kite remained immobile, which
      was suggestive of feigning death in sternal recumbency. Once the bird was perched
      upright, it immediately kept the upright position, which confirmed the
      correspondence of the bispectral index value (85) with a fully conscious patient.
      Although behavioral or cardiorespiratory variables remained unchanged, the degree
      of hypnosis was indicated by the bispectral index, which anticipated a possible
      sudden awakening episode of this bird.

PMID- 21877452
TI  - The dummies guide to promoting wildlife conservation in the Middle East: telling
      tales of unicorns and ossifrages to save the hawk and leopard.
AB  - In the Middle East there are great pressures on the environment and wildlife.
      Indeed, many species are teetering on the edge of extinction. Wildlife health,
      management, and welfare are poorly understood concepts and are not important
      priorities for regional governments. What can be done to raise the level of
      awareness to wildlife health, management, and welfare in a region where most
      people live in large modern cities detached from nature? In this article, I
      relate the story of how a small group of colleagues and I harnessed our
      frustration at the pervasive indifference to conservation to positive effect. We
      took action to establish Wildlife Middle East News, an information resource to
      raise awareness of conservation issues and to enable better management and
      welfare of wildlife. This case study demonstrates how individuals, such as
      biologists, veterinarians, and environmental educators working with wildlife in
      narrow professional arenas can play a role in the solution of wider environmental
      problems.

PMID- 21877453
TI  - When needy wildlife happens: do you run with it or punt?

PMID- 21877454
TI  - Precepting--a key nursing role.

PMID- 21877455
TI  - The necessity of collaboration.

PMID- 21877456
TI  - Motivational Interviewing in Dialysis Adherence Study (MIDAS).
AB  - OBJECTIVE: To examine the feasibility and efficacy of a staff-delivered
      motivational interviewing technique on treatment, diet, medication, and fluid
      adherence in adult patients receiving outpatient hemodialysis. DESIGN: A pre-post
      design was used for this pilot study. SAMPLE/SETTING: Twenty-nine participants
      were recruited from a non-profit, free-standing hemodialysis clinic in the
      central United States. METHODS: Prior to and after the three-month motivational
      interviewing intervention, three months of adherence data and the Health Care
      Climate Questionnaire (HCCQ) were collected. RESULTS: Motivational interviewing
      appeared to influence dialysis attendance, frequency of shortened treatments, and
      phosphorous and albumin levels favorably while less favorably impacting
      interdialytic weight gain. Changes in the HCCQ scores were not statistically
      significant from pre- to post-intervention, though the trend was in the direction
      of improvement in autonomy support, a main component of motivational
      interviewing. Patients and staff found the approach acceptable. CONCLUSIONS:
      Motivational interviewing shows promise as an intervention to improve adherence
      in adults undergoing hemodialysis.

PMID- 21877457
TI  - Striving to be heard and recognized: nurse solutions for improvement in the
      outpatient hemodialysis work environment.
AB  - One group of nurses not frequently studied but who have felt the burden of
      shortages of registered nurses (RNs) is that of nephrology nurses. Nurses'
      valuable insights must be solicited for the accurate assessment of current work
      environment issues and for their specific solutions. The purposes of this study
      were to explore nurse satisfaction and dissatisfaction with the work environment
      in outpatient hemodialysis facilities, to solicit nurses' insights on potential
      solutions, and to develop national strategies for improvement. Focus group
      qualitative methodology was utilized with focus groups and individual interviews,
      including a total of 101 RN participants from 45 outpatient hemodialysis
      facilities. The overall category of this study was Striving to be Heard and
      Recognized with the following four supportive categories: Maintaining Competency,
      Resolving Staffing and Resources, Strengthening Organizational Leadership, and
      Rebuilding Relationships. Nephrology nurse participants have identified
      strategies within each category for the improvement of their work environment.
      The voices of nephrology nurses must be heard and acted upon in a timely manner
      to improve workplace environment.

PMID- 21877458
TI  - Successful aging theory and the patient with chronic renal disease: application
      in the clinical setting.
AB  - As life expectancies increase, nurses will care for more individuals with chronic
      conditions, one of which is chronic renal disease. Increasing diversity and
      complexity of older adult healthcare needs signals a need to reconceptualize
      perceptions of successful aging. By emphasizing health promotion and adaptation,
      successful aging is possible for those with chronic renal disease. This article
      provides an overview of theory-based strategies for fostering successful aging in
      the patient with chronic renal disease.

PMID- 21877459
TI  - Medication considerations for patients with chronic kidney disease who are not
      yet on dialysis.
AB  - Because the kidney plays a large role in the absorption, distribution,
      metabolism, and elimination of drugs, significant medication-related problems can
      result from failure to properly adjust medications in patients with chronic
      kidney disease. It is the responsibility of all healthcare providers to be aware
      of necessary dose adjustments when reviewing medications, assessing drug therapy,
      changing drug therapy, or prescribing new medications.

PMID- 21877460
TI  - Electronic medical records: a survey of use and satisfaction in small dialysis
      organizations.
AB  - Little is known about electronic medical record (EMR) use in small dialysis
      organizations (SDOs). The objective was to determine the prevalence of EMRs in
      SDOs in the United States. A random sample telephone survey of SDOs was conducted
      in October, 2008. Approximately 60.7% of the facilities was found to be using an
      EMR, but only 33.5% had comprehensive systems that recorded medications, tests,
      and clinical notes. While 75.3% of the respondents indicated they were satisfied
      or very satisfied with their EMRs, just over one-third of those said they were
      planning to upgrade or replace their current systems.

PMID- 21877461
TI  - A nursing tsunami: implementing an agenda for change.

PMID- 21877462
TI  - Teaching dialyzer designers of the future.

PMID- 21877463
TI  - Withdrawal and withholding of medical treatment: Czech medical law at the
      crossroads.
AB  - The making of an end of life decision represents worldwide one of the most
      difficult issues that physicians can be confronted with --not only should it be
      regarded as consisting of medical and legal aspects, but ethics and moral values
      are present as well. Furthermore, it shall not be supposed that the economic
      parameter is negligible, unfortunately even to the contrary. The fact that the
      decision is often made by physicians under pressure caused by a system of limited
      resources (and therefore it can not avoid being distorted) must be kept in mind.
      At any rate , according to Czech law under which neither assisted suicide nor
      euthanasia is allowed, the legality and legitimacy of withdrawal and withholding
      of medical treatment is based on the argument of informed consent of the patient,
      advanced directives and the standard of lege artis treatment. These also shall be
      pleaded as defences in eventual criminal proceedings.

PMID- 21877464
TI  - Compliance with international standards on patients' rights and implementation of
      the Law on the Protection of Patients' Rights in the Republic of Macedonia.
AB  - In 2008, Macedonia adopted the Law on the Protection of Patients' Rights. This
      was a big step forward in the field of health care and regulation of patients'
      rights and responsibilities, as well as the rights and responsibilities of the
      health care providers. The Law introduces some new patients' rights (for example,
      right to second expert opinion) and new mechanisms for protection of patients'
      rights (Councilors for protection of patients' rights, Commissions for promotion
      of patients' rights). As this paper shows, the implementation of this Law is
      lagging behind. This paper argues that, besides a good law and political will, a
      continuous promotion of patients' rights and lifelong training of health care
      professionals is key to achieving promotion and protection of patients' rights in
      practice. The paper presents the findings from the comparison of the provisions
      of the Law on the Protection of Patients' Rights and the relevant international
      documents.

PMID- 21877465
TI  - The social, moral & ethical issues raised by nanotechnology in the field of
      medicine.
AB  - The areas in medicine that are and will be influenced by nanoscale science and
      technology are stem cell research, genetic modification of human beings and the
      construction of artificial organisms. A non-negotiable moral imperative is the
      fact that the law is under an obligation to uphold the sanctity and integrity of
      the human genome which encapsulates humankind's basic genetic inheritance and
      thereby the human heritage of our species. The research possibilities opened up
      by nanoscience will push the current boundaries of life forms, because they alter
      life forms at their most basic (viz genetic) level. They empower scientists to
      create novel life forms that would not otherwise exist and they combine aspects
      of different life forms that would not otherwise be integrated. These
      groundbreaking areas of research place the scientists and their work in an area
      of moral quicksands. Research involving human design and modification places
      those scientists in a domain where current morality indicates they do not belong.
      They are literally 'playing God'.

PMID- 21877466
TI  - Italian ethical committee intervention in a case of embryo-fetal medicine.
AB  - Embryo-fetal experimentation is intuitively associated with a therapeutic intent,
      according to a consolidated line of thought on the international and national
      levels. We report on a researcher's request for Ethics Committee approval to
      perform intrauterine transplantation of stem cells via cordocentesis on a fetus
      diagnosed with dystrophic epidermolysis bullosa, using stem cells obtained from a
      sibling's umbilical cord blood. The Ethics Committee rejected the request because
      of deontological issues and clinical judgments about the potential good to be
      derived from the procedure. In particular, in this case there was no preclinical
      or animal research on the procedure, the risk factors for mother and fetus were
      unknown, there was no way to guarantee compliance with Italian laws regarding
      safety and quality of the donor cells, and there was lack of clear informed
      consent.

PMID- 21877467
TI  - Obesity surgery: French medico-legal aspects.
AB  - The demand for bariatric surgery is expected to increase. It is a procedure that
      carries a high surgical risk, and a risk of postoperative complications due to
      the pathologies associated with obesity. Obesity surgery is not classified as
      plastic surgery, but may subsequently lead to plastic surgery-type operations.
      Malpractices in the field of obesity surgery are most frequently at the pre
      operative stage. In the absence of any fault, a patient may obtain
      indemnification by "national solidarity". Physicians and surgeons have an
      obligation to be able to prove that they informed their patients properly.

PMID- 21877468
TI  - Mediation in the Belgian health care sector: analysis of a particular issue--the
      material scope of application of mediation.
AB  - In this paper, the material scope of application of mediation regulated in the
      Belgian Act of August 22nd, 2002 on Patient's Rights will be discussed in detail.
      In accordance with this Act, a mediator only has the competence to handle
      patients' complaints concerning the medical and care aspects of patients' rights,
      such as complaints relating to informed consent, access to medical files, etc. In
      practice, it has been observed that issues relating to administrative matters
      also give rise to complaints and that some patients do not know with whom they
      should lodge such complaints. Some clarification is necessary for a clear and
      proper complaints procedure that works. One possible solution is the creation of
      a single institution that would be in charge of handling both kinds of
      complaints. Such a solution has to be enacted in accordance with Belgian
      federalism.

PMID- 21877469
TI  - Relatively speaking: halachic and legal issues of gamete donation.
AB  - The dramatic increase of gamete donations, as a result of technological advances
      in assisted reproduction, has raised considerable legal and halachic issues. This
      article raises reader awareness about problems involved in gamete donation within
      Jewish law (halacha), particularly in Israel. Two core problems with gamete
      donation are: deciding the mother of the child (donor or birthing mother) and
      genetic lineage. The former is important in establishing the child's religious
      status and the latter for matters of consanguinity and incest. Anonymous gamete
      donation increases the probability of incest. Persons unaware of their biological
      heritage could unintentionally cohabit with a close family member and progeny of
      this union would be considered mamzerim. These problems may be prevented by
      legislation, registration, and greater openness by the donor and the intended
      parents of the donor conceived child. This article focuses on the halachic
      perspective of gamete donation. Since consanguinity is prohibited by most
      cultures, the implications of gamete donation are universally relevant.

PMID- 21877470
TI  - Access to abortion services: the impact of the European convention on human
      rights in Ireland.
AB  - Abortion is unlawful in Ireland except where it is necessary to save the life of
      the mother. The right to life of the unborn child is safeguarded under Article
      40.3.3 degrees of Bunreacht na hEireann (the Irish Constitution). In 2003 the
      European Convention on Human Rights was incorporated into Irish domestic
      legislation, subject to the provisions of the Irish Constitution. The aim of this
      paper is to consider the potential impact of the ECHR on access to abortion
      services within the State. This paper commences with discussion of the statutory
      prohibition on abortion and the Constitutional provisions concerning the
      protection afforded to the unborn child. It will then be necessary to examine the
      implications for Ireland of recent European Court of Human Rights' decisions, in
      particular the recent judgment in A, B & C v Ireland, regarding the right to
      legal abortions given the unique nature of the legal status of the ECHR and its
      relationship with the Irish Constitution.

PMID- 21877471
TI  - Impeding access? Stigma, individual responsibility and access to post-HIV
      exposure prophylaxis (PEP) in South Africa.
AB  - Opponents of rights-based access to health care services often emphasize
      individual responsibility for health and well-being, in justifying restrictions
      on public health care. Where individuals are co-responsible for their ill health,
      so the argument goes, the public obligation to alleviate their hardship should be
      limited. This discourse not only denies the socially determined nature of
      individual behaviour and systemic factors that impact on population health, but
      also exacerbates the stigmatization of the ill. As such, it is inimical to a
      human rights approach to health. Unfortunately, it pervades much of health law
      and policy, especially in relation to HIV/AIDS. This article conducts a human
      rights analysis of access to postexposure prophylaxis (PEP) treatment for HIV in
      South Africa. It criticizes the manner in which current South African law and
      policy in this regard prioritizes access to treatment by persons who display
      characteristics of'appropriate victimhood', while discouraging access by those
      regarded as co-responsible for their illness and accordingly as undeserving of
      treatment. Ultimately, the article advocates for broader and de-stigmatized
      access to PEP in the public and private health sectors.

PMID- 21877472
TI  - Can hospitals prohibit euthanasia? An analysis from a European human rights
      perspective.
AB  - At present, in four European countries euthanasia and/ or physician assisted
      suicide (PAS) are tolerated under strict legal conditions. However, in practice
      these patient groups are often deprived of the possibility to undergo such
      decisions. Particularly Catholic health care institutions have developed policies
      which restrict the internal application of the law. Yet, the legitimacy of such
      policies is questionable. From a European human rights perspective it can be
      defended that the freedom of association allows hospitals to develop policies
      elaborating their ethical stances on euthanasia and PAS. However, to respect the
      patient's right to self-determination the concerned hospitals should at least
      inform current and future patients about the restrictive policy and deal
      carefully with euthanasia and PAS requests. If a patient's wish remains seriously
      incompatible with the ethical stances of the hospital, at least reasonable and
      attainable alternatives (such as a referral to a tolerant regional hospital)
      should be offered.

PMID- 21877473
TI  - Betrayal. Protecting people's privacy on scene.

PMID- 21877474
TI  - Does the bogeyman cometh? Mandatory paramedic program accreditation looms ahead.

PMID- 21877475
TI  - Families to the left. An exposure to an unknown substance at a school brings out
      worried parents.

PMID- 21877476
TI  - Environmental emergencies. Don't let tunnel vision cloud your judgment.

PMID- 21877477
TI  - The supervising EMS officer. What values and competencies does an EMS supervisor
      need to succeed?

PMID- 21877478
TI  - Capnography as a clinical tool. The capnography waveform is a key vital sign when
      determining treatment for patient in the field.

PMID- 21877479
TI  - The immune system and immunologic complications. Our immune system is designed to
      protect us from harmful pathogens: here's what you need to know about how it
      works.
AB  - Marie considers the exam and history findings and constructs her reply to the
      patient's statement that he does not want to go to the hospital. "Sir", she says,
      "I appreciate that you think this is just a stomach bug, but here's what I'm
      concerned about: Your lupus and the Imuran and prednisone you take to treat it
      weaken your immune system. And, with your history of diverticular disease, I'm
      worried that you may have developed diverticulitis, which your weakened immune
      system might struggle to fight effectively. Worst case scenario, you could be
      developing an infection that you cannot effectively fight. This infection could
      get worse, spread to other places in your abdomen or even your blood, and make
      you very sick. For that reason, I recommend that you go to the hospital for an
      evaluation." Presented with this information, the patient agrees to transport
      with the EMS crew to the local ED. He is placed on the cardiac monitor and IV
      access is initiated. He is monitored during an uncomplicated trip to the
      receiving ED. Later, the attending physician informs Marie and Don that the
      patient had diverticulitis with a perforated diverticula, was likely developing
      peritonitis, and had been admitted to the hospital for treatment and observation.

PMID- 21877480
TI  - Better connected. East Baton Rouge Parish medics are helping patients get
      lifesaving care faster.

PMID- 21877481
TI  - Long-distance intubation. Saving lives with telemedicine.

PMID- 21877482
TI  - DHS working toward multi-band radios. Agencies will be able to communicate
      seamlessly across bands.

PMID- 21877483
TI  - LifeBot's DREAMS takes to the HP slate tablet PC.

PMID- 21877485
TI  - Diving emergencies. Understanding concepts related to diving will prove valuable
      in case of emergency.

PMID- 21877484
TI  - Transition series: topics for the EMT. Part 4: Orthopedic trauma.

PMID- 21877486
TI  - Death after life. Years of censoring sadness can leave us tongue-tied when the
      loss is our own.

PMID- 21877487
TI  - Menninger clinic looks to build something bigger in Texas.

PMID- 21877488
TI  - Transforming our thinking about psychiatric medications.

PMID- 21877489
TI  - 2011 Behavioral healthcare champions.

PMID- 21877490
TI  - Mobilizing in a mental health crisis.

PMID- 21877491
TI  - TBI: the disability in disguise.

PMID- 21877492
TI  - Sustainable funding: from dream to reality.

PMID- 21877494
TI  - Solutions from out of the blue.

PMID- 21877493
TI  - Test customers demand more tests, more results, faster than ever.

PMID- 21877495
TI  - Court ruling ends long local fight over mental health housing.

PMID- 21877496
TI  - Reflecting on social justice.

PMID- 21877497
TI  - The new wave of SGAs.

PMID- 21877498
TI  - Dispelling disinformation in the vitamin D controversy.

PMID- 21877499
TI  - Aquatic antagonists: how to surgically remove a fishhook.

PMID- 21877500
TI  - What is your diagnosis? Labial lichen planus.

PMID- 21877501
TI  - Kaposi sarcoma presenting as yellow-green penile plaques in a black man with HIV.
AB  - Kaposi sarcoma characteristically presents with violaceous papules, plaques, or
      nodules due to the vascular nature of the lesions. We present the case of a human
      immunodeficiency virus (HIV)-positive black man with yellow-green penile plaques.
      Biopsy results revealed leukoedema and slitlike vascular spaces.
      Immunohistochemistry was positive for CD31 and CD34. He was treated with highly
      active antiretroviral therapy (HAART) and the penile plaques improved. Localized
      yellow-green penile plaques are an uncommon presentation of the well-known
      clinical entity, Kaposi sarcoma. This case underscores the varied clinical
      presentations that can occur in skin of color and the importance of
      histopathology in the assessment of uncharacteristic clinical presentations,
      especially in immunosuppressed patients.

PMID- 21877502
TI  - Pemphigoid gestationis: a case report and review of the literature.
AB  - Pemphigoid gestationis (PG) is an uncommon autoimmune bullous disease that almost
      exclusively presents during pregnancy. Patients typically present with a diffuse
      blistering and intensely pruritic eruption that begins periumbilically and
      spreads to involve the rest of the body. Direct immunofluorescence demonstrating
      C3 in a linear pattern along the dermoepidermal junction confirms the diagnosis
      of PG. Corticosteroids remain the choice of therapy and early intervention is
      essential because of possible adverse effects of PG on the fetus. We report a
      case of PG and review the literature.

PMID- 21877503
TI  - Angular cheilitis, part 2: nutritional, systemic, and drug-related causes and
      treatment.
AB  - Angular cheilitis (AC) is associated with a variety of nutritional, systemic, and
      drug-related factors that may act exclusively or in combination with local
      factors. Establishing the underlying etiology of AC is required to appropriately
      focus treatment efforts.

PMID- 21877504
TI  - An update on the presence of psychiatric comorbidities in acne patients, part 1:
      overview of prevalence.
AB  - Acne vulgaris (AV) is a chronic inflammatory skin disease that affects millions
      of people. Psychologic disorders such as depression, anxiety, and body dysmorphic
      disorder (BDD) are common in patients with AV This article in a 2-part series
      provides a review of the rates of general psychologic comorbidity, depression,
      anxiety, and BDD.

PMID- 21877505
TI  - Current regimens and guideline implications for the treatment of actinic
      keratosis: proceedings of a clinical roundtable at the 2011 Winter Clinical
      Dermatology Conference.
AB  - United States guidelines for the treatment of actinic keratosis (AK) are out of
      date. A consensus roundtable of 5 thought leaders in dermatology was held in
      January 2011 to review U.S. and European guidelines and glean from them what
      seems current and clinically applicable in the management of AK, and subsequently
      recommend what therapies may need to be added. Current AK treatments, including
      sequential therapy of various treatment options, and any new agents in
      development were also taken into consideration.

PMID- 21877506
TI  - Unilateral multisegmental morphea.
AB  - There are 5 subtypes of morphea that are based on disease distribution and
      presentation, including plaque, localized, generalized, linear, and deep morphea.
      We report a case of a young patient with morphea lesions in scattered locations
      confined to 1 side of the body, which we have termed unilateral multisegmental
      morphea.

PMID- 21877507
TI  - Aluminum chloride hexahydrate in a salicylic acid gel base: a case series of
      combination therapy with botulinum toxin type A for moderate to severe
      hyperhidrosis.
AB  - Hyperhidrosis is a common condition that has a tremendous impact on the quality
      of life of patients. For moderate to severe hyperhidrosis, topical aluminum
      chloride hexahydrate (AC), iontophoresis, and botulinum toxin type A injections
      are first-line therapies. Botulinum toxin type A has been a useful addition to
      the hyperhidrosis armamentarium and typically is utilized when topical therapy or
      iontophoresis have failed. Although highly effective for most patients, there
      remains a subset of patients who do not completely respond to botulinum toxin
      type A injections. For these patients, combination therapy with AC can greatly
      improve patient response. We present a case series of 10 patients with
      hyperhidrosis and a history of partial response to botulinum toxin type A
      monotherapy. With the addition of AC 15% in a salicylic acid 2% gel base, 5
      patients achieved 75% to 100% reduction in sweating and 5 patients achieved 100%
      reduction in sweating. Aluminum chloride hexahydrate in a salicylic acid gel base
      offers a novel and effective topical therapy in combination with botulinum toxin
      type A for patients with moderate to severe hyperhidrosis.

PMID- 21877509
TI  - AomegaA and professionalism in medicine.

PMID- 21877510
TI  - The care of the patient.

PMID- 21877508
TI  - An open-label, multicenter study of the efficacy and safety of an AM/PM treatment
      regimen with clobetasol propionate spray 0.05% and calcitriol ointment 3 microg/g
      in the management of plaque psoriasis.
AB  - Psoriasis is a chronic condition with serious quality-of-life ramifications.
      Dermatologists seek alternative treatments of patients with plaque psoriasis that
      provide both efficacy and safety while minimizing exposure to high-potency
      steroids that can have adverse effects following long-term use. We report an open
      label, multicenter study designed to evaluate a morning/evening (AM/PM) treatment
      regimen involving clobetasol propionate spray 0.05% and calcitriol ointment 3
      microg/g for moderate plaque psoriasis. Participants applied clobetasol
      propionate spray 0.05% in the morning and calcitriol ointment 3 microg/g in the
      evening for up to 4 weeks. Participants were evaluated at baseline, week 2, and
      week 4. The results of this study indicate that a 4-week regimen of clobetasol
      propionate spray 0.05% treatment in the morning and calcitriol ointment 3
      microg/g in the evening is efficacious and without unexpected safety issues for
      the management of moderate plaque psoriasis.

PMID- 21877511
TI  - Wisdom in medicine.
AB  - The pathway to wisdom is a crooked one. Doctors have many opportunities to become
      wiser, and may do so in different ways and to different degrees. We suggest
      several means to facilitate their passage. There remains an additional key step.
      Seeking wisdom should become embedded in the culture of medicine. This may follow
      from the types of activities discussed above. We believe that wisdom is
      underrecognized as a life goal for medical practitioners and teachers. It is the
      pinnacle that every doctor should strive to achieve.

PMID- 21877512
TI  - Osler came to Boston.

PMID- 21877513
TI  - Diagnosing the disorders of giants.

PMID- 21877514
TI  - The light switch.

PMID- 21877515
TI  - The history of tracheotomy.

PMID- 21877517
TI  - Differing accents but much to share.

PMID- 21877516
TI  - "Visionary art".

PMID- 21877518
TI  - Anxiety and depression.

PMID- 21877519
TI  - No end to the confusion.

PMID- 21877520
TI  - Taking the long view.

PMID- 21877521
TI  - The ones left behind: the experiences of young mothers with partners in prison.
AB  - Research into the families of male prisoners has largely focused on the
      experience of older prisoners' wives and prisoners' children. This small-scale
      two-stage study collected quantitative data from 26 women (aged 18 to 24) and
      carried out narrative interviews focused on the lives and experiences of 10 young
      women and their children. These interviews are reported upon within this paper.
      The study also explored perceived support needs the young women had and how these
      were being met by the Prison Advice and Care Trust, other statutory and voluntary
      agencies and social and family networks. The main findings related to the social
      support networks the young mothers had, contact with health and social care
      professionals, prison visits and family life. The women's accounts of their lives
      revealed a level of resilience whereby, in the presence of familial protective
      factors, they adapted to difficult relationships and situations in their lives.
      This study provides a new perspective into the experiences of a group of women
      who may have contact with health and social care professionals, and midwives and
      health visitors in particular. It recommends that there needs to be increased
      awareness regarding the whereabouts of partners.

PMID- 21877522
TI  - Community empowerment for health visiting and other public health nursing.
AB  - This paper explores the community empowerment aspect of health promotion, where
      social experience is a key indicator of health, from the perspective of health
      visiting and other public health nursing. This contemporary model of practice is
      put into a health promotion context by use of a slightly modified framework and
      by the inclusion of examples of methods and outcomes of practice that link
      conceptually with the health assets model and aspects of 'Big Society' thinking.
      Community development, social capital and capacity building are discussed as key
      elements of community empowerment with a 'bottom-up' agenda driven by community
      members. This concerns micro-population health gain, where the process, the
      quality of the public health nurse-community relationship, is as important as
      outcome.

PMID- 21877523
TI  - Health visitors' perceptions of their role in assessing parent-infant
      relationships.
AB  - The assessment of parent-infant relationships is an important process in
      safeguarding and promoting the health of children. There is compelling evidence
      of the importance of early attachment on the infant's neurological and emotional
      development. Health visitors are uniquely well placed to identify problems in the
      parent-infant relationship and to help improve its quality. This study explored
      health visitors' perceptions of their role in assessing and supporting parent
      infant relationships and their views of their own educational needs. Semi
      structured interviews were conducted with a purposive sample of six experienced
      health visitors. Health visitors used multiple sources of information in
      assessing parent-child relationships, including direct observation of behaviour,
      assessment of known risk factors, knowledge of norms and 'intuition'. Strategies
      to support the parent-infant-relationship included parenting support at home,
      listening support, encouraging parenting group attendance and referral to other
      support agencies. Health visitors reported a lack of training in parent-infant
      relationships. General agreement is required nationally and locally on
      educational and clinical experience prerequisites for this aspect of the health
      visitor role. Reduced client contact, as well as a lack of training in and use of
      specific 'relationship assessment' tools, may affect this. The Solihull Approach
      to mental health may be useful for informing future health visitor training and
      practice.

PMID- 21877525
TI  - Talking about weaning.

PMID- 21877524
TI  - NCT: facilitating transition.

PMID- 21877526
TI  - Specialised care for PND.

PMID- 21877527
TI  - Fitness to practise.

PMID- 21877528
TI  - Fungal biosorption--an alternative to meet the challenges of heavy metal
      pollution in aqueous solutions.
AB  - The removal of heavy metal from the environment, especially wastewater, is now
      shifting from the use of conventional methods to the use of biosorption, which
      may be defined as the binding and concentration of selected heavy metal ions or
      other molecules on to certain biological material. Although most biosorption
      research concerns metal and related pollutants, including radionuclides, the term
      is now applied for particulates and all manner of organic pollutants as well.
      Such pollutants can be in gaseous, soluble and insoluble forms. Biosorption is a
      physical process carried out through mechanisms such as ion exchange, surface
      complexation and precipitation. It is a property of both living and dead
      organisms (and their components) and has been heralded as a promising
      biotechnology for pollutant removal from solution. Various biomasses such as
      plant products (tree bark, peanut skin, sawdust, plant weeds etc.) have been
      tested for metal biosorption with very encouraging results. In this comprehensive
      review, biosorptive ability of fungal biomass toward heavy metals is emphasized.
      A detailed description of adsorption properties and mode of action of fungal
      biosorbents is offered in order to explain the heavy metal selectivity displayed
      by these biosorbents. The cell structure and cell wall of the fungal cell is
      evaluated in terms of metal sequestration. The parameters influencing the passive
      uptake of pollutants are analysed. The binding mechanism is discussed, including
      the key functional groups involved in the process. Quantification of metal
      biomass interactions is fundamental to evaluation of potential implementation
      strategies; hence sorption isotherms and sorption kinetics, as well as models
      used to characterize fungal biosorbent sorption, are reviewed. Despite the
      continuing dramatic increase in published research on biosorption, there has been
      little or no exploitation in an industrial context. Thus, the current status and
      future directions regarding biosorption at an industrial level are discussed. A
      systematic comparative review of the literature, based on the metal-binding
      capacity of fungal biomass under different conditions, is also provided. The
      problems associated with fungal biosorption are analysed and suitable remedies
      are discussed. Thus, this article reviews the achievements and current status of
      fungal biosorption technology and hopes to provide insights into future research.

PMID- 21877529
TI  - Development of an amperometric biosensor for phenol detection.
AB  - With the aim of searching for an in situ method for monitoring phenol, Agaricus
      bisporus tissue with tyrosine activity was used as a biocomponent and an oxygen
      electrode used as a transducer to develop a biosensor. The experimental
      methodology investigated the relation between dissolved oxygen and phenol
      concentration using a standard solution. Biosensor calibration was evaluated by
      studying reaction time and tissue amount necessary to promote a reliable response
      and to minimize errors. The influence of air saturation of the sample and washing
      of the electrode was also investigated. Results showed that 5 g of mushroom
      tissue with a 1 min reaction time promoted the best biosensor response within a
      phenol concentration range of 5-10 ppm. Washing of the electrode did not change
      the performance of the analysis; however, initial air saturation caused less
      variation amongst the samples.

PMID- 21877530
TI  - Innovative anaerobic/upflow sludge blanket filtration bioreactor for phosphorus
      removal from wastewater.
AB  - Phosphorus is the key element to remove from aquatic environments to limit the
      growth of aquatic plants and algae and, thus, to control eutrophication. Because
      the upflow sludge blanket filtratio' (USBF) process, without addition of metal
      salts, entails low efficiency for phosphorus removal, we added an anaerobic
      reactor to the USBF bioreactor in order to promote the simultaneous removal of
      phosphorus and nitrogen from wastewater. The results revealed that the
      anaerobic/USBF bioreactor had a phosphorus removal efficiency up to 86%, with a
      sludge retention time (SRT) of 10 days, a hydraulic retention time (HRT) of 24
      hours and an optimum COD/N/P ratio of 100/5/1. This ratio also improved the
      compaction quality of the sludge blanket in the USBF clarifier. The average
      specific phosphate uptake rate in the aerobic zone and the average specific
      phosphate release rate in the anaerobic reactor were 0.014 mg PO4-P removed/(g
      VSS x min) and 0.0525 mg PO4-P released/(g VSS x min), respectively. Secondary
      phosphorus release in the USBF clarifier was heightened with increasing HRT.
      Hence, the optimum total HRT can be selected between 16 and 24 hours based on
      effluent quality. Effluent phosphorus of about 1 mg/L was provided for wastewater
      with the COD/N/P ratio of 100/5/1 at the sludge age of 10 days and total HRT of
      16 hours. This study illustrated that the anaerobic/USBF bioreactor at the
      optimum operational conditions can be an effective process for phosphorus removal
      from municipal wastewater.

PMID- 21877531
TI  - Integration of photocatalysis and biological treatment for azo dye removal-
      application to AR183.
AB  - The feasibility of coupling photocatalysis with biological treatment to treat
      effluents containing azo dyes was examined in this work. With this aim, the
      degradation of Acid Red 183 was investigated. The very low biodegradability of
      AR183 was confirmed beforehand by measuring the biological oxygen demand (BOD5).
      Photocatalysis experiments were carried out in a closed-loop step photoreactor.
      The reactor walls were covered by TiO2 catalyst coated on non-woven paper, and
      the effluent flowed over the photocatalyst as a thin falling film. The removal of
      the dye was 82.7% after 4 h, and a quasi-complete decolorization (98.5%) was
      obtained for 10 h of irradiation (initial concentration 100 mg L(-1)). The
      decrease in concentration followed pseudo-first-order kinetics, with a constant k
      of 0.47 h(-1). Mineralization and oxidation yields were 80% and 75%,
      respectively, after 10 h of pretreatment. Therefore, even if target compound
      oxidation occurs (COD removal), indicating a modification to the chemical
      structure, the concomitant high mineralization was not in favour of subsequent
      microbial growth. The BOD5 measurement confirmed the non-biodegradability of the
      irradiated solution, which remained toxic since the EC50 decreased from 35 to 3
      mg L(-1). The proposed integrated process appeared, therefore, to be not relevant
      for the treatment of AR183. However, this result should be confirmed for other
      azo dyes.

PMID- 21877532
TI  - Fenton-biological treatment of reverse osmosis membrane concentrate from a metal
      plating wastewater recycle system.
AB  - Although reverse osmosis (RO) has been widely used in the recycling of metal
      plating wastewater, organic compounds and heavy metals in the RO concentrate are
      difficult to remove by conventional treatment. A combination process including
      Fenton oxidation and a biological aerated filter was used to treat RO concentrate
      containing complex Cu and Ni from metal plating. During the Fenton treatment, Cu
      and Ni ions were released due to degradation of organic compounds and then
      removed by pH adjustment and coagulation. The concentrate was further treated
      using by a biological aerated filter. Optimum conditions were as follows: initial
      pH of influent of 4.0; dosage of H2O2 of 5.0 mmol l(-1); ratio of n(Fe2+)/n(H2O2)
      of 0.8; precipitation pH of Cu and Ni ions of 8.0; and a hydraulic retention time
      of the biological aerated filter of 2.5 h. The results showed that concentrations
      of effluent COD, Cu and Ni ions were less than 40 mg l(-1), 0.5 mg l(-1) and 0.3
      mg l(-1), respectively; this means the treated effluent meets the emission
      standards for pollutants from electroplating set by China's Environmental
      Protection Agency.

PMID- 21877533
TI  - Rapid removal of Pb(II) from aqueous solution by chitosan-g-poly(acrylic
      acid)/attapulgite/ sodium humate composite hydrogels.
AB  - A series of novel granular chitosan-g-poly(acrylic acid)/attapulgite/sodium
      humate (CTS-g-PAA/APT/SH) composite hydrogels were successfully prepared by one
      step free radical graft polymerization and applied as adsorbents for the removal
      of Pb(II) from aqueous solution. The effects of adsorbent composition (including
      the contents of APT, SH and CTS) on adsorption capacity and adsorption rate were
      investigated in detail. Results from kinetic experiments showed that the rate of
      Pb(II) adsorption on the composite hydrogels was quite fast, that more than 90%
      of the equilibrium adsorption capacity occurs within two minutes and that the
      adsorption equilibrium could be achieved within 10 minutes. The adsorption
      kinetics fit well with the pseudo-second order equation. The introduced SH is
      helpful for both adsorption capacity and adsorption rate. The -COOH and -COO of
      PAA, -NH2 of CTS, Ph-O and -COO- of SH, as well as cation exchange and Si-OH of
      APT, participate in adsorption of Pb(II). The synergistic effect of these groups
      is responsible for the high adsorption capacity and rate.

PMID- 21877534
TI  - Characterization and quantification of the nickel resistant microbial community
      in activated sludge using 16S rDNA and nickel resistance genes.
AB  - The effect of nickel on the microbial community in the activated sludge of a
      sequencing batch reactor (SBR) reactor was investigated by continuously dosing
      nickel from 60 to 240 mg Ni(II) L(-1). The diversity of the microbial community
      was investigated by polymerase chain reaction (PCR) and denaturing gradient gel
      electrophoresis of the variable V3 region of the bacterial 16S rDNA. The
      experimental results showed that the community structure changed significantly
      after dosing with nickel with a shift in dominant species, the disappearance of
      some original species and the emergence of some new species. The existence of a
      nickel resistant gene was also investigated using PCR. The obtained nickel
      resistance gene had a maximum homology with the plasmid pMOL30 of Ralstonia
      metallidurans CH34. The quantitative real-time PCR results indicated that the
      quantity of the nickel resistance gene was related to the nickel concentration
      loaded to the reactor.

PMID- 21877535
TI  - Phosphate uptake performance of bacteria isolated from a full-scale Izmir
      municipal wastewater treatment plant.
AB  - This study investigated the phosphate uptake capacities of bacteria isolated from
      aerobic and anaerobic phosphate removal tanks at a municipal wastewater treatment
      plant in Izmir, Turkey, removing chemical oxygen demand to nitrogen (COD-N) and
      phosphorus (P) on a full-scale basis. Conventional plating techniques and an
      enrichment culture method were used to isolate the colonies, with a total of 91
      monoculture isolates from the sludge samples being subjected to phosphate uptake
      studies. A total of 64 of these isolates had high phosphate uptake capacities
      ranging from 3.7 x 10(10) to 1.0 x 10(-12) mg PO4(3-) cell(-1), and only 11 of
      the strains with high phosphate uptake were Gram-negative. The highest phosphorus
      uptake value was 3.7 x 10(-10) mg PO4(-3) cell(-1), which was achieved by Gram
      positive bacteria. Gram-negative strains were identified as Acinetobacter
      baumannii with a 99% probability and as Pseudomonas aeruginosa with a 96-98%
      probability (API 20 NE).

PMID- 21877536
TI  - An alternative method of particulate fluorescent tracer analysis in sediments
      using a microplate fluorimeter.
AB  - Conservative particulate fluorescent tracers (e.g. luminophores and microspheres)
      are commonly used in a wide range of sediment transport studies. Traditionally,
      their spatial redistribution is estimated by counting them in sediments under
      ultraviolet light (e.g. by epifluorescence microscopy), a time-consuming but
      effective method. While alternative methods have recently been developed (e.g.
      photodetection, digital image analyses), this 'classical' counting method remains
      the most commonly used. This article describes an alternative procedure for
      measuring the concentration of fluorescent tracers (here, microspheres) using a
      microplate fluorimeter. This technique enables simultaneous analysis of numerous
      samples while reducing the sediment preparation and quantification time. After a
      calibration step from sediment samples with known microsphere content, the method
      was validated by comparing results from the epifluorescence microscopy method.
      Different adjustments were also reported, as well as application examples. The
      different calibration tests showed high linear relationships between the
      microsphere concentration of sediment samples and the measured fluorimetric
      intensities (R2-0.99) with a detection limit of 6%. In comparison with the
      previously used method, very similar results were obtained, as illustrated in
      recent studies using both luminophores and microspheres. The rapid and reliable
      method proposed here will enable increasingly complex experiments to be performed
      with less time-consuming qualitative analyses.

PMID- 21877537
TI  - Properties and performance of silver-based catalysts on the catalytic oxidation
      of toluene.
AB  - Catalytic oxidation of volatile organic compounds such as toluene over a range of
      silver-based catalysts has been carried out to assess their performance. The
      properties of the catalysts were determined by the Brunauer-Emmett-Teller method,
      X-ray diffraction, and temperature-programmed reduction. The experimental results
      revealed that the catalytic activity of an Ag/gamma-Al2O3 catalyst is closely
      related to the silver loading, and the optimum loading for the complete oxidation
      of toluene was found to be 11 wt%. The addition of copper to the 11 wt% Ag/gamma
      Al2O3 catalyst greatly enhanced its catalytic activity, but the addition of
      cerium or lanthanum inhibited catalytic activity.

PMID- 21877538
TI  - Sorption of heavy metal metatartrate complexes on polystyrene anion exchangers.
AB  - The performance of polystyrene anion exchangers in purifying wastewaters
      containing metatartaric acid and heavy metal ions (especially those from
      electroless plating processes) was investigated. The following anion exchangers
      were selected: Lewatit MonoPlus M 500, Lewatit MonoPlus MP 64, Lewatit MP 62 and
      Amberlite IRA 402. A batch method was used to study the influence of: phase
      contact time (1-120 min); solution pH (2-9); concentration of initial heavy metal
      Cu(II), Zn(II), Co(II) and Ni(II) complexes (1.25 x 10(-4) M to 8.0 x 10(-3) M);
      temperature (303-333K); and interfering ions (Cl-, NO3-, SO4(2-), Ca2+, Mg2+).
      The amounts of Cu(II), Zn(II), Co(II) and Ni(II) complexes with metatartaric acid
      sorbed at equilibrium using the strongly basic anion exchanger Lewatit MonoPlus M
      500 were equal to 7.25 mg/g, 3.21 mg/g, 3.78 mg/g and 3.98 mg/g, respectively.
      The equilibrium sorption capacity increased slightly with increasing temperature.
      The optimal pH sorption was found to be 6.5. The experimental data were analysed
      using the Langmuir and Freundlich models. The maximum adsorption capacities q(0)
      determined from the Langmuir adsorption equation equal to 7.53 mg/g, 3.75 mg/g,
      3.55 mg/g and 4.60 mg/g were in good agreement with the experimental values for
      Lewatit MonoPlus M 500. The kinetic data obtained at different concentrations
      were modelled using pseudo first order, pseudo second order and intraparticle
      diffusion equations. The experimental data were well described by the pseudo
      second order kinetic model.

PMID- 21877539
TI  - Shell thickening and chambering in the oyster Crassostrea gigas: natural and
      anthropogenic influence of tributyltin contamination.
AB  - Abnormal thickening and chambering in Crassostrea gigas oysters have been adopted
      for many years as bioindicators of available tributyltin (TBT) in coastal waters.
      Nevertheless, since natural causes can also induce the formation of multiple
      chambers, a field study and laboratory experimentation has been conducted with 72
      examples of C. gigas in successive culture media. This work has enabled
      differences to be established between natural fine sediment-induced
      characteristics and the influence of TBT on the shells. External shell
      deformities have been assessed using three biometric indices, shell thickness
      index, weight index and volume index. Internal differences have been observed in
      longitudinal sections of the shell: retraction of growth, stagnation of the
      adductor muscle scar and thinning of the chambers in the TBT-polluted shell
      secretion. A new index, the opening chambers index, has been proposed, with a
      value of less than 1 in the TBT-polluted environment and greater than 1 in shells
      secreted in an unpolluted production site. These conclusions should be borne in
      mind when C. gigas is used in biomonitoring programmes.

PMID- 21877540
TI  - Application and evaluation of AERMOD on the assessment of particulate matter
      pollution caused by industrial activities in the Greater Thessaloniki area.
AB  - Industrial activities are sources of high emission rates of particulate matter.
      The existence of many such industrial plants close to a densely populated area
      can have a severe effect on human health. The effects can be even worse when
      these emissions are added to existing background concentration levels. This study
      deals with the assessment of the primary particulate matter pollution caused by
      industrial activities close to the city of Thessaloniki in Greece. An atmospheric
      dispersion and regulatory model was employed, i.e. AERMOD from the US
      Environmental Pollution Agency. A new PM10 emission sources inventory was
      prepared for the main industrial plants of the area and the annual and monthly
      average concentrations from 2003 to 2007 were calculated. The results from AERMOD
      were validated against data from available monitoring stations and showed
      reasonably good agreement. It was estimated that industry contributes
      approximately 30% of primary PM10 on the western suburbs of the city and about 7%
      in the city centre. The effect of the wind direction was also studied and it was
      illustrated that the frequent southwest winds present higher concentration levels
      than the strong north ones.

PMID- 21877541
TI  - Effectiveness of copper and zinc ions in preventing scaling of drinking water.
AB  - This paper investigates the effectiveness of copper and zinc ions an economical
      and environmentally friendly method for inhibiting the scaling of drinking water,
      using the method of rapid controlled precipitation (RCP). The results indicated
      that zinc ions and copper ions, at low concentrations, were highly efficient
      inhibitors in a 300 mL solution (calcium ion concentration of 126.5 mg/L). To
      produce an inhibition efficiency of 100% (in 70 min), the concentration of the
      copper ion was 0.9 mg/L and that of the zinc ion was 0.4 mg/L. The analysis by
      SEM and infrared absorption spectrometry showed that copper and zinc ions could
      affect the calcium carbonate germination and change the crystal morphology, which
      indicated that copper and zinc ions had participated in the composition of the
      crystal; however, the quantity of copper or zinc ion in the precipitate was so
      small that it was difficult to observe them.

PMID- 21877542
TI  - Biological treatment of mixtures of toluene and n-hexane vapours in a hollow
      fibre membrane bioreactor.
AB  - Membrane bioreactors are gaining interest for the control of contaminated air
      streams. In this study, the removal of toluene and n-hexane vapours in a hollow
      fibre membrane bioreactor (HFMB) was investigated. The focus was on quantifying
      the possible interactions occurring during the simultaneous biotreatment of the
      two volatile pollutants. Two lab-scale units fitted with microporous
      polypropylene hollow fibre membranes were connected in series and inoculated with
      activated sludge. Contaminated air was passed through the lumen at gas residence
      times ranging from 2.3 to 9.4 s while a pollutant-degrading biofilm developed on
      the shell side of the fibres. When toluene was treated alone, very high
      elimination capacities (up to 750 g m(-3) h(-1) based on lumen volume, or 1.25 g
      m(-2) h(-1) when normalized by the hollow fibre membrane area) were reached. When
      toluene and hexane were treated simultaneously, toluene biodegradation was
      partially inhibited by n-hexane, resulting in lower toluene removal rates. On the
      other hand, hexane removal was only marginally affected by the presence of
      toluene and was degraded at very high rates (upwards of 440 g m(-3) h(-1) or 0.73
      g m(-2) h(-1) without breakthrough). Overall, this study demonstrates that
      mixtures of toluene and n-hexane vapours can be effectively removed in hollow
      fibre membrane bioreactors and that complex biological interactions may affect
      one or more of the pollutants undergoing treatment in gas-phase membrane
      bioreactors.

PMID- 21877543
TI  - Investigation into the artificial ageing effects on the microstructure of an
      industrial solid waste treated with cement.
AB  - Metal hydroxide sludges are classified as hazardous wastes in the European
      Hazardous Waste Catalogue (EHWC) because of their high heavy metal contents (Zn,
      Cr, Fe, Cu, etc.) and the release of these pollutants to the environment.
      Thereby, the disposal of this waste without any treatment is a substantial
      environmental problem. Stabilization/solidification technologies are widely used
      for the treatment of wastes and residues in order to obtain inert materials. This
      work aims to assess the effectiveness of the chemical fixation and solidification
      of a metal hydroxide sludge generated by the electrotyping surface treatment
      industry, using Portland Artificial Cement. In order to predict the medium- and
      long-term behaviour of the solidified waste, an artificial ageing by means of
      thermal shocks and humidity variation cycles was applied. Scanning Electron
      Microscopy (SEM) and X-ray Diffraction studies revealed a considerable increase
      in calcite within the solid matrix after the artificial ageing, which can be
      attributed to the phenomenon of carbonation. It was also found that the
      mechanical properties of the solidified material, after ageing, were improved by
      up to 30%.

PMID- 21877544
TI  - Effect of incineration temperature on phosphorus availability in bio-ash from
      manure.
AB  - In the near future phosphorus (P) will be a limited resource in high demand. This
      will increase the incentives for recycling P in animal manure. In this study the
      dry-matter-rich fraction from slurry separation was incinerated and the P
      availability of the ash fraction examined. The aim was to adjust incineration
      temperature to support a high plant-availability of P in ash. The plant
      availability of P was approximately halved when the incineration temperature was
      increased from 400 to 700 degrees C. This decrease in plant-availability was
      probably due to the formation of hydroxyapatite. Incineration temperatures should
      therefore be kept below 700 degrees C to ensure a high fertilizer efficiency of P
      in ash. This may conflict with the energy production, which is optimal at
      temperatures above 800 degrees C. An alternative to incineration may therefore be
      thermal gasification of the dry-matter-rich fraction, which can be carried out
      efficiently at lower temperatures.

PMID- 21877545
TI  - Evaluation of snail shell as a coagulant aid in the alum precipitation of aniline
      blue from aqueous solution.
AB  - The present studies aimed to evaluate the potential of snail shell (SS) as a
      coagulant aid in the alum precipitation of aniline blue (AB), an acid dye, from
      an aqueous system. The proximate physico-chemical characteristics of the SS were
      determined, and the results obtained showed that the pH(solution) was 8.01, the
      SS was made up of a high fraction of inorganic constituents (ash content of
      93.76%), Ca2+ was present as the major metal ion (99.74%), and the point of zero
      charge (PZC) was found to be at pH 7.9. The mineralogical assemblage was studied
      using an X-ray diffractometer, and the results obtained revealed the presence of
      aragonite. The stability and leaching of the SS, tested in different aqueous
      media (acidic, basic and neutral solutions) showed that the SS was less stable in
      the acidic medium. Both alum and SS were used, differently, for dye
      precipitation. The use of alum alone showed no precipitating effect on the AB dye
      molecules, whereas SS alone was able to reduce the dye concentration
      considerably. When the SS was used as a coagulant aid in alum precipitation, the
      percentage of the AB dye molecule removed increased. The effects of some process
      variables (coagulant/coagulant aid dosage, pH and flocculation time) were
      optimized by the method of continuous variation. The results obtained showed that
      an appreciable amount of the AB dye molecules was abstracted across the pH range,
      but the highest value was achieved at the lowest pH values. Studies on the effect
      of time on the flocculation of the precipitated AB molecule showed that the
      problem of redispersion and restabilization encountered in alum precipitation
      could be overcome using an alum-SS combination. The settling characteristics of
      the sludge obtained from the use of SS alone and an alum-SS combination were
      studied by measuring the sludge volume index (SVI, mg/g) over time. The value of
      the SVI showed that the sludge produced from the alum-SS combination had better
      settling characteristics than the sludge from the use of SS alone. Subsequent to
      the results obtained from the present studies, the use of the SS as a coagulant
      aid in the alum precipitation of the anionic dye as a unit process tertiary
      method of treatment in a suspended-growth wastewater treatment system was
      proposed.

PMID- 21877546
TI  - Proposal for a screening test to evaluate the fate of organic micropollutants in
      activated sludge.
AB  - The concentrations of organic micropollutants are usually low in wastewaters
      (order of magnitude of mg L(-1)). However, their emission standards, especially
      in the case of carcinogenic and bioaccumulating substances, are often much lower
      (order of magnitude of microg L(-1)). Since these substances, in some cases, can
      be adsorbable or volatile, their removal via volatilization, biodegradation or
      sludge adsorption in a wastewater treatment plant (WWTP) becomes a significant
      feature to include in the usual design process, in order to verify the emission
      standards in gas and sludge too. In this study a simple screening batch test for
      the evaluation of the fate of organic micropollutants in water, air and sludge is
      presented. The test is set up by means of simple laboratory instruments and
      simulates an activated sludge tank process. In this study the results obtained
      for four substances with different chemical properties (i.e. toluene,
      benz(a)anthracene, phenol and benzene) are presented. The screening test proposed
      can be a useful tool to assess in about one month the fate of organic
      micropollutants in an activated sludge tank of a WWTP. Moreover, the test can
      constitute a useful support in the use of mathematical models, since it allows
      the verification of model results and the calibration of the reactions involved
      in the removal process.

PMID- 21877547
TI  - Microorganism communities and chemical characteristics in sludge-bamboo charcoal
      composting system.
AB  - Microorganism communities and chemical characteristics in sludge-bamboo charcoal
      composting system were investigated to find the effect of bamboo charcoal on
      composting. According to a plate count test, abundances of bacteria, fungi and
      actinomycetes in the treatment with bamboo charcoal were several times higher
      than those in treatment without bamboo charcoal. In addition, terminal
      restriction fragment length polymorphism (TRFLP) analysis indicated that the
      bacterial community diversity in treatment with bamboo charcoal was greater than
      that of the control. Both results demonstrated that amendment with bamboo
      charcoal can increase microorganism population and microorganism community
      diversity in a sludge composting system. Moreover, the results of FTIR
      spectroscopy disclosed that aerobic composting can promote the formation of
      surface acid groups on bamboo charcoal. These surface acid groups may deprotonate
      and react with NH4+ to form stable complexes. Therefore, the increase of
      functional groups accompanied with greater assimilation of nitrogen by
      microorganisms could reduce nitrogen loss in sludge composting.

PMID- 21877548
TI  - Organochlorine pesticides removal from wastewater by pine bark adsorption after
      activated sludge treatment.
AB  - Pesticides have been responsible for strong environmental impacts, mainly due to
      their persistence in the environment. Removal technologies are usually combined,
      because degradation of organic matter is needed prior to a tertiary treatment to
      guarantee pesticides elimination to levels below legal limits (normally 0.1
      microg L(-1)). Pine bark was studied as an alternative to activated carbon, for
      organochlorine pesticides removal. A combination of technologies based on
      biodegradation with activated sludge followed by pine bark adsorption treatment
      was used for lindane (LIN) and heptachlor (HEP) removal from contaminated waters.
      Pesticides were quantified throughout the process by GC-ECD preceded by solid
      phase microextraction (SPME). An experimental set-up was maintained for 4 months,
      by feeding a standard solution with pesticides concentration of 1 microg L(-1)
      each and known organic matter (Chemical Oxygen Demand, COD, -563 mg O2 L(-1)) on
      a daily basis. COD suffered a reduction of about 81% in the biological step and
      no increase was detected in the subsequent adsorption treatment. Overall removal
      efficiency was 76.6% and above 77.7% for LIN and HEP, respectively.

PMID- 21877549
TI  - Hydroxycobalamin, hyperbaric oxygen and cyanide poisoning.

PMID- 21877550
TI  - Wind, waves and weekend warriors: the heart of the matter.

PMID- 21877551
TI  - Hyperbaric oxygen therapy or hydroxycobalamin attenuates surges in brain
      interstitial lactate and glucose; and hyperbaric oxygen improves respiratory
      status in cyanide-intoxicated rats.
AB  - Cyanide (CN) intoxication inhibits cellular oxidative metabolism and may result
      in brain damage. Hydroxycobalamin (OHCob) is one among other antidotes that may
      be used following intoxication with CN. Hyperbaric oxygen (HBO2) is recommended
      when supportive measures or antidotes fail. However, the effect of
      hydroxycobalamin or HBO2 on brain lactate and glucose concentrations during CN
      intoxication is unknown. We used intracerebral microdialysis to study the in vivo
      effect of hydroxycobalamin or HBO2 treatment on acute CN-induced deterioration in
      brain metabolism. Anesthetized rats were allocated to four groups receiving
      potassium CN (KCN) 5.4 mg/kg or vehicle intra-arterially: 1) vehicle-treated
      control rats; 2) KCN-poisoned rats; 3) KCN-poisoned rats receiving
      hydroxycobalamin (25 mg); and 4) KCN-poisoned rats treated with HBO2 (284 kPa for
      90 minutes). KCN alone caused a prompt increase in interstitial brain lactate and
      glucose concentrations peaking at 60 minutes. Both hydroxycobalamin and HBO2
      abolished KCN-induced increases in brain lactate and glucose concentration.
      However, whereas HBO2 treatment increased cerebral PtO2 and reduced respiratory
      distress and cyanosis, OHCob did not have this beneficial effect. In conclusion,
      CN intoxication in anesthetized rats produces specific uncoupling of cerebral
      oxidative metabolism resulting in interstitial lactate and glucose surges that
      may be ameliorated by treatment with either hydroxycobalamin or HBO2.

PMID- 21877552
TI  - Effects of immune reaction in rats after acute carbon monoxide poisoning.
AB  - This study is designed to observe the immune reaction in rats after acute carbon
      monoxide (CO) poisoning. We observed brain injury, cognitive impairment, a
      variety of microglias and expression of immune factors, including major
      histocompatibility complex II (MHCII), CD4, vascular cell adhesion molecule-1
      (VCAM-1) and interferon-gamma (IFN-gamma) in the brain tissues of CO-poisoned
      rats. Then relationships between cognitive impairment and immune factors were
      explored. We found that there were extensive neuronal degeneration and necrosis
      in the brains of CO-poisoned rats, and the escape latency of the CO Group in a
      Morris water maze became significantly longer than that of the Control Group
      (11.63 +/- 3.54s vs. 7.06 +/- 3.13s, p < 0.05) after six days of CO poisoning.
      Microglias, as immune effector cells, underwent activation and proliferation
      which reached 35.0 +/- 5.7 cells per five high-power fields (HPF) in the seventh
      day after CO poisoning, but 20.3 +/- 2.9 cells/5HPF in the Control Group (p <
      0.05). Expression levels of immune factors increased in the brains of CO-poisoned
      rats. VCAM-1-positive cells peaked in quantity the first day, IFN-gamma-positive
      cells and MHCII-positive cells the third day and CD4-positive cells the seventh
      day. The results indicate that immune reaction plays an important role on CO
      mediated neuropathology.

PMID- 21877553
TI  - The history of hyperbaric oxygen therapy and kidney transplant surgery.

PMID- 21877554
TI  - Recreational diving fatalities.
AB  - The risks of dying during recreational diving are small. The Divers Alert Network
      (DAN) held a workshop to consider whether the risks could be reduced further.
      Topics included investigation, surveillance, operational safety and
      cardiovascular disease. Investigation is essential to determine causes and
      involves on-scene inquiry, forensic examination of the deceased, and testing of
      life support equipment, but thorough investigations are unusual. Independent
      annual fatality rates were presented and reviewed for diving, jogging, and motor
      vehicle accidents and for divers in training. Common factors associated with
      diving fatalities included running out of gas, entrapment or entanglement,
      buoyancy control, equipment misuse, rough waters and emergency ascent. Asphyxia
      by drowning, air embolism and cardiac events were the principal injuries or
      causes of death. About one-quarter of the deaths were associated with cardiac
      events, mostly in older divers. Revised procedures were recommended for
      identifying occult cardiovascular disease in candidate divers who warrant further
      investigation, but older, previously certified divers may be at greatest risk.

PMID- 21877555
TI  - The cardiovascular system and diving risk.
AB  - Recreational scuba diving is a sport that requires a certain physical capacity,
      in addition to consideration of the environmental stresses produced by increased
      pressure, low temperature and inert gas kinetics in tissues of the body. Factors
      that may influence ability to dive safely include age, physical conditioning,
      tolerance of cold, ability to compensate for central fluid shifts induced by
      water immersion, and ability to manage exercise demands when heart disease might
      compromise exercise capacity. Patients with coronary heart disease, valvular
      heart disease, congenital heart disease and cardiac arrhythmias are capable of
      diving, but consideration must be given to the environmental factors that might
      interact with the cardiac disorder. Understanding of the interaction of the
      diving environment with various cardiac disorders is essential to providing a
      safe diving environment to individual divers with known heart disease.

PMID- 21877556
TI  - The cardiovascular risks of diving.
AB  - Cardiovascular disease may be responsible for a quarter of diving fatalities, but
      there are few studies on the cardiovascular complications of this activity. In
      contrast, there is a rich literature on land-based, exercise-related cardiac
      events. These studies document that exercise can increase the risk of acute
      cardiac events, but that absolute risk is small for healthy individuals. There
      are no proven strategies to reduce exercise-related cardiac events and
      consequently no proven strategies that could be confidently applied to diving.
      Nevertheless, requiring a pre-diving medical evaluation and clearance for those
      with known cardiac disease, training dive personnel to elicit possible cardiac
      prodromal symptoms, and frequent emergency training for diving supervisors are
      prudent approaches to this problem.

PMID- 21877557
TI  - Cardiovascular screening in asymptomatic adults: lessons for the diving world.
AB  - At the broadest level, consensus preparticipation recommendations for athletes of
      all ages focus on performance of a history and physical examination, with the
      additional performance of a screening test being more controversial. Depending
      upon athlete age and the associated prevalence of etiologies of cardiac death,
      differences exist regarding specific targets for the history and physical and for
      the type of testing considered. This paper provides a summary of the estimated
      relative value of the components of a screening program for both younger and
      older athletes.

PMID- 21877558
TI  - Medical screening of recreational divers for cardiovascular disease: consensus
      discussion at the Divers Alert Network Fatality Workshop.
AB  - Cardiac events are responsible for a significant proportion of recreational
      diving fatalities. It seems inescapable that our current systems for selecting
      suitable recreational diver candidates and for longitudinal monitoring of diver
      health are failing to exclude some divers at high risk of cardiac events. Based
      on review of practice in parallel sporting disciplines and of the relevant
      literature, a series of recommendations for screening questions, identification
      of disqualifying conditions and risk factors, and investigation of candidates
      with risk factors was drafted. Recommendations for ongoing health monitoring in
      established divers were also generated. These recommendations were promulgated
      and debated among experts at a dedicated session of the Divers Alert Network
      Fatality Workshop. As a result, we propose a modified list of screening questions
      for cardiovascular disease that can be incorporated into health questionnaires
      administered prior to diver training. This list is confluent with the American
      Heart Association (AHA) preparticipation screen for athletes. The exercise stress
      test unmasks inducible cardiac ischemia and quantifies exercise capacity, and
      remains the tool of choice for evaluating diver candidates or divers with risk
      factors for coronary disease. An exercise capacity that allows for sustained
      exercise at a 6-MET intensity (possibly representing a peak capacity of 11-12
      METS) is an appropriate goal for recreational divers.

PMID- 21877559
TI  - Hyperbaric oxygen treatment to eliminate a large venous air embolism: a case
      study.
AB  - Gas embolism, the entry of gas into vascular structures, can result in serious
      morbidity and death. It is an inadvertent clinical problem, but it also occurs in
      non-clinical environments. Gas embolisms result from procedures performed in
      almost all clinical specialties, thus making it a problem about which all
      clinicians should be aware. In most cases, gas embolism is air embolism, although
      it can result from the introduction of gases such as carbon dioxide, nitrous
      oxide and nitrogen. Gas embolism takes two forms, venous and arterial,
      distinguished by the mechanism of gas entry and the site where the emboli
      ultimately lodge. Techniques used to eliminate embolisms including administration
      of 100% oxygen, placing the patient in lateral decubitus, and Trendelenburg
      position for no longer than 10 minutes, removing the embolism with a catheter,
      surfactants and hyperbaric oxygen therapy (HBO2T). For venous gas embolisms
      surgical removal is recommended, while for arterial embolisms, HBO2T is highly
      recommended. Here we report on a patient who inadvertently received a venous
      infusion of 150 ml air resulting in a major embolism, and who underwent HBO2T,
      recovered well, and suffered no adverse events. This result suggests that it is
      important to consider HBO2T as a recommended application for patients with venous
      embolisms.

PMID- 21877560
TI  - Fostering connections and practice change.

PMID- 21877561
TI  - The educational experiences of former foster youth three years after discharge.
AB  - This article presents three years of outcome data that describe the educational
      and vocational experiences of a sample of foster youth discharged from a
      residential education program (n = 106). Of respondents, 33% were attending
      college at each of the four data collection points, which was far below the
      stated aspirations of 80% of the youth to attend college. An additional 10-15%
      were in a vocational training program. Of the sample, 13% initially entered a
      four-year college, but it was not possible to confirm whether they continued
      attending a four-year school for longer than two years. Community college
      attendees were more likely to remain in school than four-year attendees. The
      policy and practice implications of these findings are discussed.

PMID- 21877562
TI  - After family treatment drug court: maternal, infant, and permanency outcomes.
AB  - This study reports on maternal functioning, infant developmental, and permanency
      outcomes for 52 families following maternal participation in a family treatment
      drug court (FTDC) for perinatal substance users. Although the majority of
      families experienced positive child welfare outcomes, over time, maternal
      functioning deteriorated and infant developmental concerns were identified. Even
      when promising interventions like FTDC are used, long-term needs of families
      affected by perinatal substance use need to be considered and addressed.

PMID- 21877563
TI  - Preventing child abuse and neglect: a national evaluation of Parents Anonymous
      groups.
AB  - This evaluation assessed whether participation in Parents Anonymous mutual
      support groups was associated with child maltreatment prevention. Parents new to
      groups across the United States were interviewed at baseline, one month, and six
      months. Using standardized scales, all parents showed improvements in some child
      maltreatment outcomes, risk factors, and protective factors. Parents starting out
      with particularly serious needs showed statistically significant improvement on
      every scale. Results indicated that Parents Anonymous participation contributes
      to child maltreatment reduction.

PMID- 21877564
TI  - Foster care transition services for youth with disabilities: findings from a
      survey of county service providers.
AB  - This study explores the transition services available for youth with disabilities
      in foster care and the collaboration among foster care transition programs with
      other types of providers. Findings from this survey of independent living
      coordinators working for child welfare agencies indicate that while youth with
      disabilities are being served through transition programs and these programs
      collaborate with other government agencies, there are few services targeted
      directly toward their needs, little collaboration with community-based agencies,
      and a need for more information sharing.

PMID- 21877565
TI  - Workforce retention issues in voluntary child welfare.
AB  - Unlike many studies focused on retention and turnover in public child welfare,
      this study examined issues of job satisfaction and retention in voluntary child
      welfare. Although three-fourths of the 1,624 workers surveyed intended to remain
      in child welfare, 57.3% had thought about leaving their agencies during the past
      year. All respondents were dissatisfied with their level of pay, but those
      thinking of leaving were significantly less satisfied with the contingent rewards
      they received.

PMID- 21877566
TI  - Is vicarious trauma the culprit? A study of child welfare professionals.
AB  - This article reports on a qualitative, multicase study of child welfare
      professionals who discussed the changes they experienced because of the work they
      do. It was concluded that vicarious trauma was the cause. This study was grounded
      in the constructive self-development theory, a developmental and interpersonal
      theory with a trauma focus that explains the impact of trauma on an individual's
      psychological development, identity, and adaptation.

PMID- 21877567
TI  - [Current developments in parents-baby psychotherapy].

PMID- 21877568
TI  - [Attachment and attachment-based intervention: the Circle of Security
      intervention project in Hamburg].
AB  - Since the early sixties empirical research into early childhood and the parent
      infant relationship has increased, commonly informed by attachment theory. The
      mutually regulated interaction within the attachment and care giving relationship
      of mother and infant gives this relationship its exceptional emotional quality.
      Early attachment experiences organize socio-emotional and cognitive development
      beyond childhood. Attachment theory and research define observable behaviors and
      the level of internal representations as an intervening variable of the
      transmission of attachment patterns between mother and child. Basic attachment
      derived concepts are the starting points of the Circle of Security approach. The
      Circle of Security Intervention Project in Hamburg for mothers with postpartum
      mental illness and their infants is described in more detail. Specific aspects
      are discussed with reference to a diagnostic case study.

PMID- 21877569
TI  - [How much food for a soul? Psychosomatic treatment of infantile feeding
      disorders].
AB  - Severe feeding disorders often require inpatient treatment and need a holistic
      assessment and treatment approach. This article introduces some of the current
      literature concerning feeding disorders in infants and toddlers. The philosophy
      of the Department of Infant Psychosomatics at the University Children's Hospital
      Zurich emphasizes interdisciplinary teamwork, the application of psychodyamic
      tools in pediatric liaison psychiatry and utilization of group settings. Clinical
      approach and course of treatment are illustrated by three case reports,
      highlighting specific psychotherapeutic interventions with the parent-infant
      relationship in the context of a paediatric clinic.

PMID- 21877570
TI  - [An interdisciplinary approach to parent-child therapy with complex and severe
      feeding difficulties].
AB  - Our interdisciplinary team is based in a teaching hospital department for
      psychosomatics and therapeutic interventions for mothers and children. This
      tertiary service provides assessment and treatment of infants, children and their
      families presenting with complex and severe feeding disorders. We specialise in
      the care of children with a variety of multiple problems e. g. presenting after
      premature birth, and their associated relationship problems. The complexity of
      issues requires intervention at multiple levels in order to address the
      individual and family needs of the child. Each case represents opportunities and
      challenges. The team also addresses integrated services provision across the
      spectrum of services involved as well as attempting to integrate therapeutic
      approaches across professional boundaries. This is illustrated by a case report
      and complemented by a literature review.

PMID- 21877571
TI  - [How to involve fathers in parent-infant therapy].
AB  - This paper deals with the role of fathers within a context of parent-infant
      counseling or therapy. A review of the evidence regarding father-infant
      interaction and of fathers' involvement in therapeutic intervention is
      complemented by a case vignette of a young family. It illustrates the different
      personal characteristics of each parent in their family interaction and
      delineates options for therapists, notably the useful potentials of fathers.

PMID- 21877572
TI  - Strengthening Papua New Guinea's health system.

PMID- 21877573
TI  - Demography and the epidemiology of disease in Papua New Guinea.
AB  - Papua New Guinea (PNG) remains a predominantly rural society. Declining mortality
      but only slow decline in fertility has led to an average annual growth rate of
      the order of 2.8%. If fertility continues to decline slowly, the population will
      reach 10 million soon after 2029; with an accelerated decline the population will
      be about 8.9 million persons in 2029. Wide differentials in mortality among
      provinces indicate considerable variation in mortality change. Infectious
      diseases which dominate the cause structure of mortality should be susceptible to
      health service intervention. Prerequisites are an appropriate mix of
      interventions, high levels of coverage, and high-quality monitoring and
      surveillance. It is critical that these unsolved disease problems be fully
      addressed as the combination of increasing urbanization, the AIDS (acquired
      immune deficiency syndrome) epidemic and an increasing prevalence of non
      communicable diseases will place upward pressure on mortality rates. For the
      purposes of monitoring mortality change health services need access to methods
      for the calculation of mortality rates which have been validated in populations
      in PNG. Perhaps the most fundamental task of health services is to prevent
      unnecessary deaths. This article focuses on levels of mortality and the cause
      structure of mortality. It examines the relationship between health service
      interventions and mortality decline in PNG.

PMID- 21877574
TI  - Beyond the numbers: Papua New Guinean perspectives on the major health conditions
      and programs of the country.
AB  - How members of the community perceive and respond to diseases and health problems
      are important variables to take into account when planning interventions and
      priorities in a health system. This paper summarizes some qualitative research
      undertaken in 2001 and 2002 in Papua New Guinea as part of the formative research
      for health promotion activity development for immunization, maternal health,
      tuberculosis and malaria services. It provides some highlights of the health
      beliefs and health-seeking behaviours amongst a range of urban and rural
      populations in a range of provinces in Papua New Guinea (PNG), and across a range
      of age groups including young adults. The findings reinforce that these health
      related issues are seen by most of the population as important, although maternal
      health lags behind, especially in male respondents' perspectives. However, how
      they respond varies often with the planned health system interventions, and these
      differences need to be understood and addressed in order to increase the
      acceptability and efficiency of health services in PNG.

PMID- 21877575
TI  - Working together to get back to basics--finding health system solutions.
AB  - This paper highlights the key changes to the health system over the past 20
      years, including the impact of the Organic Law on Provincial Governments and
      Local-level Governments, the politicization of the system, the changing balance
      between government and development partners in financing the health system, and
      the development of a sector-wide approach in the Papua New Guinea health sector.
      It discusses reform efforts at bureaucratic and regulatory level to address these
      problems. Key health sector policy issues and lessons learned over the past two
      decades are highlighted. The paper concludes with an examination of what is
      needed to 'get back to basics' through mobilizing all health sector partners with
      the aim of getting the health system delivering improved health outcomes.

PMID- 21877576
TI  - The primacy of politics: charting the governance of the Papua New Guinea health
      system since independence.
AB  - To chart the course of health governance in Papua New Guinea (PNG) since
      Independence, this article identifies two arks of public sector administration in
      PNG. Each was instigated by the passing of an Organic Law. The reform periods
      presaged by the Organic Law on Provincial Government 1976 (OLPG) and the Organic
      Law on Provincial Governments and Local-level Governments 1995 (OLPGLLG) have
      fundamentally transformed the political and administrative structures governing
      the country, and in particularly those relating to health. Comparing the
      organization of the government-operated health system during each of these reform
      periods not only reveals why PNG's health services have struggled to improve
      since Independence, but also casts light on the key drivers of fundamental
      reforms in PNG. Ultimately, the exercise illustrates the 'primacy of politics',
      and why political concerns invariably trump service delivery concerns.

PMID- 21877577
TI  - Human resource development: new assessments and new directions.
AB  - The National Health Plan (NHP) 2001-2010 required a health workforce situation
      analysis and strategy to match the NHP's priorities and strategies. This paper is
      based on the work that was done in 2001 to support the preparation of a Health
      Human Resource Development Strategy for Papua New Guinea (PNG). The analysis
      showed that changes in health sector financing, population growth and changing
      health needs had created many human resource problems and challenges. This paper
      focuses on the main categories of health worker in PNG: doctors, health extension
      officers, nurses and community health workers. It presents analyses of workforce
      numbers and costs, and discusses future health system and human resource
      strategies based on the 2001 study and subsequent developments.

PMID- 21877578
TI  - Persistence as the path from motivation to performance in the Papua New Guinea
      health sector.
AB  - This paper considers how the individual capacity states of motivation,
      confidence, skill and ability relate to performance, and identifies a crucial
      role for the discretionary behaviour of individuals: specifically, employee
      persistence and innovation. The study Understanding the people and performance
      link: unlocking the black box undertaken by Purcell and colleagues is relied upon
      in constructing a theoretical framework for the conceptual interrelationships
      between performance and the human-resource-mediating variables, which is then
      applied within the Papua New Guinea (PNG) health sector context. The study by
      Purcell and colleagues, which was informed by organizations with well-developed
      and functioning human resource policies and practices, is distinguished from the
      PNG health sector, where human resource frameworks are largely ineffective--yet
      it is determined that the importance of 'discretionary behaviour' relative to
      performance, whilst varied, is undiminished.

PMID- 21877579
TI  - Public-private partnerships for health--what does the evidence say?
AB  - This paper provides an overview of the literature regarding public-private
      partnerships (PPPs) by examining several case studies from around the world and
      documenting the lessons learned across different PPP models. In addition, it
      focuses on experience in the facilitation of two PPPs between the public and
      private sectors in Papua New Guinea (PNG) and discusses the potential benefits
      that may be delivered to PNG communities through pursuing further such PPPs for
      health.

PMID- 21877580
TI  - Working together for a better future.
AB  - In this review we reflect upon the papers within this focus issue of the Papua
      New Guinea Medical Journal on the theme of health system strengthening, and
      provide a summary of lessons learnt and ways forward from the lessons and
      experiences of the past. Priority areas have been identified for consideration by
      the health sector and its various players and stakeholders moving forward,
      particularly in the context of the next National Health Plan. The imperative need
      to focus on the basics is emphasized: to make sure that key health interventions
      are implemented; that health workers have requisite skills and are placed where
      services are needed; that there is an uncompromising focus on ensuring, by
      whatever means, that the essential logistical elements are there to enable the
      health worker to provide the interventions; that key messages are communicated
      to, and provide support for, communities to attend care and practise health
      promoting behaviours; and that population coverage is increased. The need for a
      long-term, systematic approach to getting the basics in place is essential. In
      developing and implementing this approach, caution needs to be taken with regard
      to confusion between means and ends. It is important to maintain focus on the
      desired outcome--improved health of Papua New Guineans; and to use, but not be
      distracted by, the means for getting there--including the various health sector
      reforms being implemented. It is essential to identify and focus on ways in which
      the existing capacity within the system can be harnessed, and to ensure that the
      environment supports the effective and efficient use of existing capacities. The
      capacity of the health sector--and the careful, measured use of partnerships--to
      extend service delivery to underserved populations is discussed in broad terms.

PMID- 21877581
TI  - [Molecular targeted therapies in gastroenterological cancers].

PMID- 21877582
TI  - [Surgical treatment for severe congestive heart failure--surgical
      ventriculoplasty, artificial heart, heart transplantation].

PMID- 21877583
TI  - [N staging of non-small cell lung cancers--communication of the upper lobe with
      the mediastinum and minimal N2 disease].

PMID- 21877584
TI  - [Management of chronic intractable pain].

PMID- 21877585
TI  - [Dr Leonor Michaelis and early days of Hokkaido University School of Medicine;
      episodes among three medical researchers in the roaring twenties].
AB  - Little has been known about the personal history of Dr. Takaichi Mohri
      (Nakashima), the first professor of department of hygiene at Hokkaido University
      School of Medicine. We, therefore, have been inquiring academic backgrounds of
      Dr. Mohri for two decades. These inquiries show interesting episodes between Dr.
      Leonor Michaelis, one of the biggest names in enzymologists, and early days of
      this Medical School. In this article, we describe that at least two professors,
      Drs. Takaichi Mohri and Kaoru Ohguro, were in good acquaintances with Dr.
      Michaelis as follows; 1) the latter half of 1921, Dr. Ohguro visited a laboratory
      of Dr. Michaelis in Berlin, 2) from November 1922 to June 1923, Dr. Michaelis in
      Nagoya collaborated with Dr. Mohri in Sapporo, 3) Dr. Michaelis in Nagoya visited
      Dr. Ohguro's house and office in Sapporo at March 1925, and 4) at the same
      occasion, Dr. Michaelis made his lecture on biochemistry in Hokkaido University
      School of Medicine. Since Drs. Ohguro and Mohri were classmates of the University
      of Tokyo Faculty of Medicine, Dr. Ohguro could introduce Dr. Michaelis to Dr.
      Mohri who used to be a graduate student in department of biochemistry. As a
      result of relationships, Drs. Michaelis and Mohri published a paper entitled
      "Eine weitere Methode zur Bestimmung des isoelektrischen Punktes von
      Eiweisskoerpern und ihre Anwendung auf die Serumalbumine verschiedener Tiere" in
      Biochemische Zeitschrift, which was a part of Dr. Mohri's Ph.D. thesis.

PMID- 21877586
TI  - Reliability and validity of Kano Test for Social Nicotine Dependence (KTSND), and
      development of its revised scale assessing the psychosocial acceptability of
      smoking among university students.
AB  - PURPOSE: To examine reliability and validity of Kano Test for Social Nicotine
      Dependence (KTSND), a scale assessing the psychosocial acceptability of smoking,
      and to develop a new version when validity or reliability of KTSND was not
      acceptable. METHODS: We carried out a self-administered cross-sectional survey on
      undergraduate university students. The participants completed the KTSND, and
      supplemented three questions on the attitudes toward tobacco control policies and
      smoking states. Using daily smokers, we examined the relationship between the
      KTSND and Fagerstrom Test for Nicotine Dependence (FTND). In each study, we
      examined test-retest reliability and construct validity, discriminant and
      convergent validity, and factor validity. RESULTS: Although the KTSND had high
      internal consistency (Cronbach's a 0.82) and high test-retest reliability
      (r=0.72), the results of factor analysis were unacceptable; we expected three
      factors to be extracted, however, only two factors of "Overestimate of smoking
      usefulness" and "Allege smoking as a taste and/or culture" were extracted. Using
      the Kano's Test for Assessing Acceptability of Smoking (KTAAS), the new version
      of KTSND in which a question was replaced with another one, the third factor of
      "Neglect of harm of tobacco smoking" was extracted adding to the above-mentioned
      two. KTAAS had also both high internal consistency (Cronbach's alpha 0.82) and
      test-retest reliability (r=0.66). Overall, the KTSND and the KTAAS score differed
      according to smoking states, and the nonsmokers' scores were the lowest.
      CONCLUSION: The KTSND was a popular questionnaire in Japan, however, its validity
      assessed using factor analysis was not acceptable, while KTAAS had sufficient
      reliability and validity, and might assess the cognition and attitude affirming
      or accepting tobacco smoking among university students.

PMID- 21877587
TI  - Chassin, Loeb cite high reliability as 'next stop' of QI journey.
AB  - Leadership, culture of safety, robust process improvement are key elements of
      creating high reliability, experts say. High level of safety must be maintained
      over a long period of time over all of the facility's services. New methods of
      calculation are required to accurately measure the level of reliability that has
      been achieved.

PMID- 21877589
TI  - Palliative care hardwired into hospital system.

PMID- 21877588
TI  - Teamwork key part of heart failure initiative.
AB  - Program improves compliance from 60% to 85% of patients receiving all appropriate
      care. Teamwork helps to identify goals and helps patients meet those goals.
      Physician leadership, hands-on nursing care, and education are critical
      ingredients for success.

PMID- 21877590
TI  - EDs taking on the issue of chronic pain.

PMID- 21877591
TI  - Silent PPOs--what they are and how to handle them.

PMID- 21877592
TI  - [The past, the present and the future of renal replacement therapy].
AB  - The observation that renal failure leads to 'uraemia' through retention of
      solutes that would otherwise be excreted by healthy kidneys, has been formulated
      as early as the first half of 19th century. The discovery of osmosis and a
      colloid membrane facilitated the first testing ofdialysis, originally in animals
      and in the first quarter of 20th century also in humans. In the mid 1940s,
      dialysis became the method of choice for the treatment of acute renal failure. At
      the beginning of 1960s, the development of long-term venous access made
      programmes of chronic haemodialysis possible in many countries. These
      achievements, together with kidney transplantation, saved or significantly
      extended life of millions of patients with chronic renal failure. The last 50
      years saw a dramatic increase in the number of chronically dialyzed patients; the
      safety and efficacy of haemodialysis methods improved and effective treatments
      have been introduced of a number of complications associated with chronic renal
      failure (e.g. hypertension, anaemia or bone disease). Despite this, mortality of,
      particularly older chronically dialyzed patients, is very high and their quality
      of life sometimes low. High cardiovascular mortality, frequently due to chronic
      heart failure and sudden death (unlike ischemic heart disease in healthy
      population), is a dominating problem. However, it is difficult to reduce the high
      cardiovascular morbidity and mortality of haemodialyzed patients. Patient
      prognosis might probably be improved by more frequent use of convective methods
      of blood purification and frequent haemodialysis as well as effective management
      ofdyslipidemia. Nevertheless, early diagnosis of patients with chronic renal
      insufficiency and early management of all general as well as renal failure
      specific risk factors in patients with mild to moderate chronic renal
      insufficiency is essential if the prognosis ofhaemodialyzed patients is to be
      improved. Future developments of renal replacement therapies are difficult to
      predict. The treatment should be individualized; early transplantation,
      peritoneal or home (frequent) haemodialysis should be performed in younger
      patients and conservative treatment, in addition to chronic haemodialysis, should
      be used in older patients. Miniaturization as one of the potential future trends
      could facilitate the use of portable artificial kidney. Artificial membranes
      coated with proximal tubule cells and ex vivo kidney cultivation represent
      another interesting perspective.

PMID- 21877593
TI  - [Aetiology and a clinical picture of chronic renal failure].
AB  - The term chronic renal failure (CRF) usually means the final stage of chronic
      kidney disease (CKD) with a decline in glomerular filtration rate (GF) below 0.25
      mL/s. CRF is a world-wide serious health and economic issue with an increasing
      incidence and prevalence. CRF patients are, in comparison to other patients,
      hospitalized more often and for longer and, despite improvements in care, their
      quality of life is usually low and morbidity and mortality high. We present an
      overview of the most important CKD risk factors and the diseases most likely to
      result in CRF. Diabetic nephropathy, followed by various forms ofischemic renal
      disease and primary and secondary glomerulopathy, chronic tubulointerstitial
      nephritis and autosomal dominant polycystic kidney disease are the leading causes
      of CRF. We provide a brief overview of other disease states that may result in
      renal failure. Clinical manifestations of CRF are discussed, mainly
      cardiovascular, gastrointestinal, haematological and neurological symptoms.
      Breathlessness is a consequence of hypervolaemia, metabolic acidosis and anaemia.
      The disease often presents with symptoms, such as headache and visual
      disturbances, resulting from arterial hypertension. Gastrointestinal symptoms and
      fatigue, usually caused by anaemia, are frequent. Platelet dysfunction is
      manifested as an increased bleeding time. Paradoxically, apart form tendency to
      abnormal bleeding, CRF also tends to be associated with thromboembolic
      complications. Patients may experience itching, bone, joint and muscle aches, are
      more prone to infections. They may suffer from insomnia, concentration disorders
      and apathy. The signs of peripheral mixed sensory-motor neuropathy include
      paraesthesia, paresis and restless leg syndrome. However, renal failure may also
      be oligosymptomatic or asymptomatic. Cardiovascular complications are the most
      frequent cause of morbidity and mortality of CRF patients.

PMID- 21877594
TI  - [Hypertension and cardiovascular complications of chronic renal failure].
AB  - Chronic renal failure is associated with a significant cardiovascular risk due to
      an increased incidence of cardiovascular risk factors (hypertension, diabetes
      mellitus, dyslipidemia). Cardiovascular mortality is due to an increased
      incidence of left ventricular hypertrophy, ischemic heart disease and chronic
      heart failure. Management focuses on risk factors, mainly high blood pressure in
      patients with mild to moderate chronic kidney disease, but it often fails in
      patients with chronic kidney failure.

PMID- 21877595
TI  - [Bone disease in chronic renal failure and its modern therapy].
AB  - Renal bone disease is one of the most serious complications of chronic renal
      failure. Secondary hyperparathyreosis is decisive for its pathogenesis. Current
      prevention and treatment emphasises pathogenetic and clinical interrelationships
      between bone tissue involvement and cardiovascular complications (CKD-MBD, bone
      and venous involvement associated with chronic renal disease). The treatment
      should first correct hyperphosphatemia and, subsequently, hyperreactivity of
      parathyroid glands through vitamin D receptor (VDR) and calcium receptor (CaR)
      modulation. Three groups of drugs play a fundamental role here (GIT phosphate
      binders, calcimimetics and vitamin D receptor activators). Certain other
      therapeutic approaches are used in some specific situations such as, among
      others, refractory hyperparathyreosis or calciphylaxis.

PMID- 21877597
TI  - [Anemia and chronic kidney failure].
AB  - Anaemia is a common manifestation ofa chronic kidney failure. It is caused by a
      relative shortage oferythropoetine (EPO) and iron deficite with its metabolism
      defect. The most important factor in the pathogenesis of iron metabolism defects
      is hepcidin. Hepcidin maintains the iron homeostasis in the organism. The therapy
      of renal anaemia is based on the iron substitution and erythropoiesis stimulating
      agents (ESA) application. The most common reasons for the resistance to ESA are
      (after iron deficiency) inflammation and malnutrition.

PMID- 21877596
TI  - [Urinary tract infections and chronic renal failure].
AB  - The paper briefly summarizes issues related to urinary tract infections in
      adults: predispositions and risk factors, classification, assessment of
      pathogenicity of bacterial agents, the role of bacteriuria and leucocyturia,
      interpretation of findings, treatment principles and an association with chronic
      renal failure. Urinary tract infections are the second most frequent infectious
      disease in the population. They most often affect women of childbearing potential
      and then seniors of both sexes who have multiple risk factors. Escherichia coli
      and Staphylococcus saprophyticus are the most pathogenic towards urinary tract;
      they are responsible for 85% and 10-15% of cases of acute uncomplicated urinary
      infections, respectively. Chronic pyelonephritis, a chronic interstitial
      nephritis, is the fourth most frequent cause of chronic renal failure. Chronic
      renal failure is a risk factor for the development of urinary infections due to
      metabolic disorders resulting in secondary immunodeficiencywith a disorder of all
      components of immunity. In patients with chronic renal failure, urinary tract
      infections occur most frequently after kidney transplantation when graft
      pyelonephritis is a life-threatening complication. Therefore, urinary tract
      infection prevention with co-trimoxazole once daily over at least 6 months is
      recommended in renal allograft recipients.

PMID- 21877598
TI  - [Peritoneal dialysis and its modification in the treatment of chronic renal
      failure].
AB  - Three methods can be used to treat chronic renal failure - haemodialysis,
      peritoneal dialysis and renal transplantation (from a living donor or
      transplantation of a cadaver kidney). In 2009, 5,763 patients were treated with
      haemodialysis in the Czech Republic, while peritoneal dialysis was used in just
      8% (458) of patients. This low number of peritoneal dialyses may be due to the
      still high number of chronic renal failure patients who come to dialysis centres
      "offthe street". Following acute initiation of haemodialysis, these patients are
      usually retained on haemodialysis. Poor awareness of peritoneal dialysis among
      patients as well as health care professionals is another reason for the low
      number of peritoneal dialysis patients. Peritoneal dialysis is suitable for home
      treatment. Peritoneum serves as the dialysis membrane, peritoneal cavity is
      filled with dialysis solution and the metabolism waste products and water are
      excreted into this solution. A base to correct metabolic acidosis then passes
      from dialysis solution into the body. Permanent catheter is inserted into the
      abdominal cavity to enable infusion of the dialysis solution. The dialysis is
      continual and this ensures stability of the inner environment and thus most
      closely resembles own kidney function. The advantages of peritoneal dialysis
      include longer preservation of residual renal function, inner environment
      stability and no need for venous access. Peritoneal dialysis is associated with a
      lower risk of infections. Peritoneal dialysis is contraindicated in patients
      after an extensive intraabdominal surgery and in patients with a stoma.
      Peritoneal damage is a serious complication of peritoneal dialysis; the risk
      increases with the treatment duration and thus peritoneal dialysis is not a long
      term treatment choice. With the traditional CAPD (continual ambulatory peritoneal
      dialysis), the patient performs an exchange ofdialysis solution him/herself4 to 5
      times a day. With APD (automated peritoneal dialysis) a machine performs dialysis
      solution exchanges, dialysis is performed at night and the patient may engage in
      other activities during a day. From the perspective of log-term survival of
      patients with chronic renal failure, peritoneal dialysis appears to be the method
      of choice. The patient is first treated with peritoneal dialysis and subsequently
      receives a transplant. Should the renal allograft be rejected, the patient
      returns to the dialysis programme, either peritoneal or haemodialysis. Patients
      should be provided with true and objective information about their disease and be
      informed about all treatment options for chronic renal failure. The choice of
      method has to be tailored to the overall health status of the patient as well as
      his/her lifestyle.

PMID- 21877599
TI  - [Haemodialysis - the current practice].
AB  - New techniques and technological innovations developed over the last decades have
      facilitated improvements in haemodialysis. An emphasis is on an early insertion
      of arteriovenous fistula as a venous access for haemodialysis. Dialysis treatment
      should be initiated when the glomerular filtration rate falls to 8-10 mL/min, and
      to15 mL/min when the patients have risk factors. Haemodialysis is usually
      performed 3 times a week for 4 hours; less frequent or shorter haemodialysis is
      acceptable only in patients with well-preserved residual renal function.
      Extending haemodialysis to 5-6 hours is useful in preventing complications.
      Haemodiafiltration with high flux membranes, more permeable for middle molecules,
      is preferred in patients with long-term haemodialysis. Correct assessment of dry
      weight, i.e. an optimal body weight after haemodialysis without any signs of
      hypervolaemia, is important. Apart from a clinical assessment, body composition
      monitor (BCM) that uses bioimpedance to assess the proportion of water in the
      body, is helpful in determining dry weight. Reduction ofdialysis solution
      temperature to 36-35 degrees C and blood volume monitor (BVM) that measures
      changes in haematocrit during water elimination, are used to prevent dialysis
      associated hypotension. Potassium profiling decreases the incidence ofarrhythmias
      in haemodialysed cardiac patients. Blood temperature monitor (BTM) is used to
      measure recirculation and thus to detect an arteriovenous fistula dysfunction.
      Protection of residual renal function through an elimination of nephrotoxic
      substances as well as prevention of hypotension and excessive ultrafiltrations is
      an important part of care for a haemodialysed patient.

PMID- 21877600
TI  - [An overview of the results of renal transplantation in the Czech Republic].
AB  - Renal (kidney) transplantation is now a routine and the most successful form of
      renal replacement therapy. There is a long tradition of renal transplantation in
      the Czech Republic, The first was performed as early as 1961 in Hradec Kralove,
      and the programme as such was launched in 1966 with the first successful
      transplantation at the Institute of Experimental Surgery (later Institute for
      Clinical and Experimental Medicine, Prague). At present, transplantations are
      being performed at 7 transplantation centres (IKEM Prague, Centre for
      Cardiovascular and Transplantation Surgery Brno, Faculty Hospitals Hradec
      Kralove, Plzen, Olomouc and Ostrava and Faculty Hospital Motol for children).
      From the programme launch until the end of 2010, 8,761 renal transplantations
      were performed, 364 in 2010 alone. One-year patient and cadaver renal allograft
      survival, transplanted in the CR between 2000 and 2009, is around 95% and 92%,
      respectively, and 5-year survival is 87% and 81%, respectively. As of 31st
      December 2009, a total of 3,771 patients lived with functional renal allograft in
      the Czech Republic and the proportion of patients with irreversible renal failure
      treated with transplantation has recently been around 40%.

PMID- 21877601
TI  - [Biological treatment following renal transplantation].
AB  - Renal transplantation represents a method of choice in irreversible renal
      failure. The outcome of renal transplantation is affected by acute or chronic
      rejection and long-term evaluation also suggest a role of adverse effects of
      immunosuppressive therapy, mainly the incidence of cardiovascular complications
      and tumours. Immunosuppressive therapy with biologic agents aims to reduce the
      incidence of acute rejections, prolong allograft survival and, consequently,
      patient survival. Apart from a reduction in acute rejection incidence, biological
      agents are used in a selected group of patients to eliminate the need for an
      adjunctive treatment with steroids and to reduce consequences of ischemic
      reperfusion damage in older donors who suffer from a range ofco-morbidities. The
      most frequently used therapies include induction and anti-rejection therapy with
      a rabbit polyclonal anti-human thymocyte globulin (rATG) or an induction therapy
      with monoclonal anti-interleukin-2 receptor antibody (anti-IL2R), basiliximab.
      Considering the high immunosuppressive effect of rATG, adverse effects, mainly
      opportunistic infections and more frequent delayed tumourigenesis, have to be
      taken into account.

PMID- 21877602
TI  - [Immunosuppressive therapy and its problems].
AB  - Immunosuppressive therapy is crucial for successful kidney transplantation.
      Induction, antirejection and maintenance immunosuppressive therapy are basic
      types of immunosuppressive therapy. Base of maintenance immunosuppressive therapy
      are corticoids + tacrolimus + mycofenolate mofetil. Short and long-term adverse
      effects are present. Drug interaction with macrolids and antimycotics are
      substantial. Cooperation between transplantologist and other specialists are
      crucial for adequate immunosuppressive therapy actualization. Lack of correlation
      and communication may lead to irrecoverable damage to transplanted kidney.

PMID- 21877603
TI  - Role of serum procalcitonin and C-reactive protein in the diagnosis of neonatal
      sepsis.
AB  - This cross sectional observational study was done in the division of neonatology,
      department of pediatrics, Bangabandhu Sheikh Mujib Medical University (BSMMU) in
      the year 2007. The study population was 50 newborns in total who needed
      evaluation of sepsis on clinical suspicion. The main objective of this study was
      to assess serum procalcitonin (PCT) as a better diagnostic marker than C-Reactive
      Protein (CRP) in neonatal sepsis. The total study populations were classified
      into 4 groups like highly probable, probable, and possible and no sepsis group
      according to the clinical and blood parameters. PCT and CRP were assessed and
      compared by statistical analysis. For the estimation of PCT and CRP, venous blood
      was drawn and centrifuged and stored at - 20 degrees C in the refrigerator. Later
      on PCT was measured by rapid semi quantitative immunochromatographic test. Level
      of CRP was determined by semi quantitative method (latex). All data were analyzed
      by SPSS version 10 windows. For statistical analysis appropriate tests were done.
      In all observations sepsis was found to be more common in male newborns and in
      those who were delivered by caesarean section. In low birth weight and preterm
      newborns sepsis was more prevalent. Premature rupture of membrane (PROM) was
      found to be the commonest maternal clinical condition as a risk factor of sepsis.
      There was positive correlation between serum PCT and CRP and values of serum PCT
      as well as CRP differed significantly in the different categories of sepsis
      indicating relation to the severity of sepsis. PCT is a useful, sensitive and
      independent biomarker of neonatal sepsis. CRP measurement along with PCT
      measurement may increase the specificity. Though PCT measurement is comparatively
      expensive but an easy bed side promt convenient procedure for sick neonates in
      addition to CRP for rapid evaluation of neonatal sepsis rather than waiting for
      the report of blood culture.

PMID- 21877604
TI  - Knowledge about inhaler use among the chronic asthma patients in selected
      hospitals.
AB  - This cross sectional descriptive study was conducted among the chronic asthma
      patients attending three Institutes of Dhaka city namely National Asthma Center,
      The National Institute of Diseases of Chest and Hospital (NIDCH), Mohakhali, and
      Dhaka Medical College Hospital to assess the level of knowledge regarding inhaler
      use. Convenient sampling was adopted. Data were collected using one semi
      structured questionnaire through face-to-face interview. The patients were aged
      from 18 to 75 years with mean age being 40.68 years and sd +/- 11.659 years. The
      mean monthly income of the respondents found was 8278.52 taka with standard
      deviation +/- 3523.315 taka. Mean duration of bronchial asthma was 9.44 years
      with sd +/- 4.862 years. Out of the total 298 respondents 103(35.8%) possessed
      "excellent knowledge" on inhalers. Ninety one (31.6%) had "adequate knowledge",
      sixty nine (24.0%) had "poor knowledge" and thirty five (8.7%) respondents were
      found having "no knowledge" about inhalers. Males were seen having better
      knowledge than the females (chi2 =66.582, df=3, p<0.001). The respondents
      receiving treatment from the indoor possessed better knowledge than those from
      the outdoors (p<0.001). Level of Knowledge was also found to be associated with
      the educational status of the respondents. Respondents with higher education
      possessed more than the respondents with lower education (p<0.001). Though most
      of the physicians now prescribe inhalers, but many of them do not explain the
      proper use of inhaler. This may be corrected through training and motivation of
      physicians at Medical Colleges and Hospitals and during various medical
      conferences and other programs. To reduce the extent of suffering and economic
      burden of asthma patients and their families, active education program for the
      patients and training program for the health care providers, regarding "inhaler
      use technique" demands early consideration.

PMID- 21877605
TI  - Predictors of depression among older people living in rural areas of Thailand.
AB  - Global population is ageing and Thailand has one of the fastest growing ageing
      populations in this region. Combined with this, depression has become a major
      mental health problem for older people. The objective of this paper is to examine
      the predictors of depression among rural older people of Thailand. This study has
      used information from the Study on Health and Social Support among Older
      Population living in Kanchanaburi Demographic Surveillance System (KDSS),
      Thailand in 2006. Depression was measured by a 12 item questionnaire of Thai
      validated Euro-D scale among 1001 respondents. The questions were on depression,
      pessimism, wishing to die, guilt, sleep disturbance, loss of interest,
      irritability, eating problems, fatigue, problem in concentration, lack of
      enjoyment, and tearfulness. Among the respondents 28.5% had depression. The
      results of logistic regression found that infirmity, disability and serious life
      events had significant effect on depression of the respondent. Those who had 4 or
      more infirmity, they were 2.08 times more likely to have depression compare to
      those who had no or only 1 infirmity. Disability was another strong predictor of
      the depression. It should be mentioned here that those who had medium disability,
      had the chance of depression 3.12 times more compare to those who had no
      disability. Serious life event was also a major factor for the respondents. Those
      who had 3 or more serious life events they had the depression 5.25 times more
      compare to those who had no serious life event.This study identified three major
      predictors of depression for older people in KDSS, Thailand. The finding will
      help to design specific prevention program to reduce the depression of older
      people living in the rural area of Thailand.

PMID- 21877606
TI  - Immature reticulocyte fraction as a predictor of bone marrow recovery in children
      with acute lymphoblastic leukaemia on remission induction phase.
AB  - Immature reticulocyte fraction a new routine parameter in the hematology analyzer
      can give the idea of the earliest morphologic change of bone marrow recovery
      before other test become positive after chemotherapy. A prospective observational
      study was carried out in the Department of Clinical Pathology in collaboration
      with Paediatric Haematology and Oncology, Bangabandhu Sheikh Mujib Medical
      University during a period of one year starting from October 2009 to September
      2010 to evaluate the bone marrow recovery in children with acute lymphoblastic
      leukaemia by automated reticulocyte analysis. Total fifty patients were enrolled
      in this study on remission induction phase. All patients were between 8 months to
      15 years age range with a mean age of 5.5 +/- 3.2. At the end of the study out of
      50 cases, 52% patients showed early immature reticulocyte fraction recovery and
      concluded that the immature reticulocyte fraction parameter showed earlier
      haematopoietic recovery than the current practice of absolute neutrophil count
      recovery.

PMID- 21877607
TI  - Acute poisoning in southern part of Bangladesh--the case load is decreasing.
AB  - This retrospective study was carried out in the Medicine Department of Khulna
      Medical College, the biggest tertiary hospital in the southern part of Bangladesh
      to observe the trends of poisoning in southern part of Bangladesh over four years
      including age and sex variation, mode of poisoning, type of poison used and
      outcome of poisoning. The hospital medical records of all patients, aged 10 years
      and above with history of acute poisoning from January, 2003 to December, 2006
      were enrolled. Patients were categorized into four age group including Group
      (Gr.) I, Gr. II, Gr. III & Gr. IV having age range of 10-20, 21-30, 31-40 & >40
      respectively. Underlying causes of poisoning were also observed totally and
      individually in different mode with male, female ratio and the percentage. Death
      cases according to mode of poisoning with demographic alignment were also
      observed. Statistical analysis were done using epi-info version 3.5.1 and
      measures were presented as proportion and percentage. Among 1903 cases, 1012
      (53.1%) were male and 891 (46.8%) female with a ratio of 1.4: 1. The year wise
      total number of cases were progressively decreased from 627 (2003) to 353 (2006).
      Most commonly found toxic agent was Organo-Phosphate compound (526; 27.64%) with
      a very little sexual variation & this trend remained same in all study years.
      Poisoning with unknown substance was the second leading cause (16.03%) followed
      by Copper-sulphate (14.03%), Sedative (13.35%), Snakebite (12.93%) etc. Incidence
      of unknown poisoning, sedatives, snake-bite and corrosives were found to be
      gradually decreased over the study years. Male were found mostly affected in
      majority type of poisoning except Copper-sulphate, kerosene, puffer fish,
      paracetamol and other drugs category. Age group II (710; 37.3%) was the most
      vulnerable group with male (57.89%) preponderance followed by group I (643;
      33.7%), III (329; 17.2%) and IV (221; 11.6%) respectively. Highest 1308 (68.7%)
      cases were suicidal in mode followed by 304 (15.9%) accidental and 291 (15.2%)
      homicidal. Out of 1903, 140 (7.3%) patients died. Death rate was highest in OPC
      poisoning (52.1%) followed by unknown substance (13.5%), snakebite and copper
      sulphate (11.4%) etc. In an agro-based country like Bangladesh, it's very
      difficult to reduce the poisoning cases and mortality. Prospectively designed
      multi-centered studies are needed to reflect the epidemiological properties of
      poisonings throughout Bangladesh, and would be very valuable for the
      determination of preventive measures.

PMID- 21877608
TI  - Eclampsia-scenario in a hospital--a ten years study.
AB  - This cross sectional record based institutional study was conducted in the
      Department of Obstetrics & Gynaecology, Burdwan Medical College, Burdwan over ten
      years (1999-2008) aiming analysis of eclamptic mothers for evaluation of maternal
      and perinatal outcome with different anticonvulsant medications. Total 5991
      pregnant mothers with eclampsia admitted in the inpatient department of the
      tertiary care teaching hospital were recruited for the study, irrespective of
      their previous antenatal check up history. Subjects with known seizure disorders
      were excluded from the study. The subjects were managed according to standard
      regimens (Menon, Ph-sodium, diazepam & magnesium sulphate) and results were
      documented in standardised format. Case fatality rate, mean induction delivery
      time & birth-weight, perinatal mortality rates were recorded. Study reveals that
      the incidence of eclampsia <20 years was 6.97% and majority (5.41%) came from
      rural areas. Eclampsia was noted primarily in primigravida (7.43%) and unbooked
      (6.41%) mothers. Ante partum eclampsia predominated (64%) and incidence of
      caesarean section was 22.25%.The overall case fatality rate was 6.05% and
      eclampsia contributed 27.85% of all maternal deaths during the last two years of
      the study period. The overall incidence of low birth weight baby was 26.96% and
      perinatal mortality was 30.33% (1411/4651).The incidence of perinatal mortality
      and low birth weight babies are lower in the last 4 years when compared to
      earlier studies. Proper socio-demographic assessment of pregnancy with eclampsia,
      planned delivery, shorter induction delivery interval, good control of convulsion
      by magnesium sulphate, intensive intranatal monitoring causes less maternal and
      perinatal morbidity and mortality.

PMID- 21877609
TI  - Psychosocial aspects of care.

PMID- 21877610
TI  - Study highlights dangers of long waits before discharge.

PMID- 21877611
TI  - Teamwork and technology produce faster trauma care.

PMID- 21877613
TI  - Volunteering for service: the role of emergency nurses.
AB  - The Order of Malta Volunteers is a Roman Catholic charity best known for
      organising pilgrimages to Lourdes for disabled people. This article offers a
      personal account of the author's experiences as head nurse of the charity, in
      Lourdes and in the wake of last year's earthquake in Haiti.

PMID- 21877612
TI  - Dealing with the effects of domestic violence.
AB  - Domestic violence has a lasting and damaging effect on the lives of thousands of
      women, men and children in Ireland and the UK. Yet, healthcare services are il
      equipped to deal with the victims of physical, sexual, and psychological abuse,
      many of whom present to emergency departments because they need help and support.
      As this article discusses, healthcare staff have a responsibility of care for
      such people. They must be able to recognise and respond to the signs of domestic
      abuse, and refer people who experience it to the appropriate organisations.

PMID- 21877614
TI  - How GPs can help reduce inappropriate attendance.
AB  - York District Hospital emergency department (ED) piloted a scheme in which GPs
      work alongside ED staff. By seeing and treating minor cases, the GPs allowed ED
      staff more time to care for acutely ill patients, thereby reducing waiting times
      and the rate of inappropriate attendance, and improving patient flow. This
      article discusses the scheme and a qualitative review of how staff perceived it.
      Findings from the review suggest that the introduction of GPs to EDs can improve
      the healthcare experience for staff and patients.

PMID- 21877615
TI  - Meningococcal disease in children: case studies and discussion.
AB  - This article is based on two case studies in which children with suspected
      meningococcal disease were brought to the author's emergency department. It
      examines the signs and symptoms of the disease, and discusses its management.
      Emergency practitioners should understand and recognise the signs and symptoms of
      serious meningococcal disease and refer children to paediatric services
      immediately.

PMID- 21877616
TI  - Stress in emergency departments: experiences of nurses and doctors.
AB  - The effects of stressful incidents on emergency department (ED) staff can be
      profound. Witnessing aggression, violence or the death of patients, or
      participating in resuscitation, can be emotionally and physically demanding.
      Despite the frequency of these events, ED staff do not become immune to the
      stress they cause, and are often ill prepared and under supported to cope with
      them. This article reports on a study of nurses' and doctors' attitudes to, and
      experiences of, workplace stress in three EDs in Ireland, and offers some
      suggestions on how stress among ED staff can be reduced.

PMID- 21877617
TI  - For patients' sake, we need a renal ACO.

PMID- 21877618
TI  - The impact of the bundle on lab services.
AB  - The rule states that CMS will implement a quality incentive program (QIP) for
      Medicare outpatient end-stage renal disease (ESRD) dialysis providers and
      facilities with payment consequences beginning January 1, 2012. This is in
      accordance with section 1881(h) of the Act (added on July 15, 2008 by section
      153(c) of the Medicare Improvements for Patients and Providers Act (MIPPA)).
      Under the ESRD QIP, ESRD payments made to dialysis providers and facilities under
      section 1881(b)(14) of the Social Security Act will be reduced by up to 2% if the
      providers/facilities fail to meet or exceed a total performance score for
      standards related to certain specified performance measures.

PMID- 21877619
TI  - CMS proposes framework for making Medicaid changes.

PMID- 21877620
TI  - Dialysis overnight: in-center nocturnal hemodialysis programs showing growth.
AB  - Toxin and fluid removal are the main goals of dialysis therapy for patients with
      end-stage renal disease. Recent data indicate that the BUN-centered delivery of
      dialysis therapy with high efficiency, conventional, thrice-weekly hemodialysis
      therapy may fall short on the likewise critically important fluid control.
      Extended hour, in-center nocturnal HD (INHD) emerges as one of the alternative
      therapies for patients whose clinical needs are not met with conventional HD or
      who are seeking a dialysis therapy less interfering with daytime activities. We
      report the logistic requirements for a nocturnal program evaluated in a pilot at
      a midsize non-profit dialysis provider. In-center nocturnal hemodialysis provides
      longer dialysis sessions similar to the thrice-weekly 8-10 hour dialysis
      treatments originally prescribed in the early days of dialysis. INHD allows for a
      more flexible lifestyle-oriented dialysis schedule and enables patients to
      maintain routine daytime activities. It also offers an alternative schedule for
      patients who require extended-hour dialysis for various medical reasons.

PMID- 21877621
TI  - Making a INHD program work at your clinic.

PMID- 21877622
TI  - Fresenius expanding INHD programs.

PMID- 21877623
TI  - Is the bundle leading to a tighter provider market? Key acquisition, merger mark
      activity in 2010-2011.

PMID- 21877624
TI  - Advocacy, access, achievement: making the connections.

PMID- 21877625
TI  - Private school nurses: reflecting on past to present.

PMID- 21877626
TI  - Preparing graduate-level school nurses for practice.

PMID- 21877627
TI  - Partnerships in special needs school nursing.

PMID- 21877628
TI  - What is the role of the state school nurse consultant?
AB  - SSNCs provide statewide nursing leadership to ensure effective school nursing
      services, develop and promote quality standards, and foster a better
      understanding regarding the role of the school nurses and the relationship
      between students' health and their ability to learn (NASSNC, 2008). SSNCs use the
      nursing process to identify goals and plan interventions for meeting those goals.
      The interventions implemented by SSNCs are state-specific and are dependent upon
      assessment findings and available resources. Currently 40 states employ SSNCs.
      States use a variety of funding resources to secure the services of SSNCs
      (Taliaferro, 2011). For tips regarding how to advocate for a State School Nurse
      Consultant in your state, visit the National Association of State School Nurse
      Consultants' website at www.nassnc.org and click on "Advocacy".

PMID- 21877630
TI  - A historical review of distance vision screening eye charts: what to toss, what
      to keep, and what to replace.
AB  - Vision screening protocol and equipment guidelines differ among schools across
      the United States. Budget cuts are forcing many school nurses to reevaluate their
      vision screening programs, as well as items in their vision screening toolboxes.
      School nurses tasked with inventorying those toolboxes to determine which items
      to toss, keep, or replace are oftentimes perplexed by the copious choices
      featured in vendor catalogs and websites. For school nurses who want their vision
      screening toolboxes to include eye charts, national and international eye chart
      design guidelines are available to help ensure selected eye charts are
      standardized. A national consensus policy exists that recommends specific eye
      charts. And, a large body of vision screening literature is available to help
      school nurses make informed decisions. Current documents suggest that LEA Symbols
      are appropriate for young children and Sloan Letters are a better choice than
      "Snellen" charts for older children.

PMID- 21877629
TI  - Managing diabetes effectively in the school setting: case studies and frequently
      asked questions.

PMID- 21877631
TI  - Tips for exercising safely in the heat: steer clear of heat cramps, heat
      exhaustion, and heat stroke with key information.

PMID- 21877632
TI  - The top 10 ... or rather the top 11 highlights of 2010-11: NASN has too much good
      news to fit in the top 10!
AB  - NASN has worked tirelessly in 2010-2011 to increase the organization's vision,
      voice, and visibility under the direction of Sandi Delack, immediate past
      president. The current officers, staff and NASN School Nurse Editorial Advisory
      Board identified what they believed to be the top 11 highlights of the past year.
      This feature is provided as a complement to the lengthier article titled "NASN
      2011: Our Annual Checkup--A Look at the Organization's Vital Statistics,"
      published in this same issue.

PMID- 21877633
TI  - Nasn 2011--our annual checkup: a look at the organization's vital statistics.
AB  - NASN continually monitors information of importance to the health of the
      organization and is dedicated to sharing this information with its stakeholders.
      Our Weekly Digest provides real-time updates in a concise manner to address the
      needs of the busy school nurse. This article, "Our Annual Checkup," will provide
      more depth and include information regarding membership and finances, as well as
      information pertaining to each area of NASN's strategic plan: Programs, Research,
      Public Relations, and Advocacy. It is the goal of NASN to utilize the July issue
      of the NASN School Nurse to provide an annual update to the membership.

PMID- 21877634
TI  - School nurse survival: reviewing clinical skills in the simulation laboratory.
AB  - School nursing is a specialty that requires nurses to provide holistic health
      care to a diverse population. Federal disability laws make it necessary for the
      school nurse to maintain and competently perform higher level technical skills-
      outside the home or hospital setting. Skills include tracheotomy care, gastric
      tube care, urinary catheterizations, central line care, oxygen delivery, ostomy
      care, and advanced assessment skills. How do school nurses maintain these skills
      if they are not used frequently enough to assure competency? The authors' college
      of nursing and a school outreach department have partnered to offer an annual
      school nurse conference. One option for participants is to use the simulation
      laboratory to refresh these skills and to review newer equipment and technology.
      The simulation laboratory staff and pediatric faculty are available to
      demonstrate and assist participants with skills technique. Participants have
      responded positively to this collaborative effort.

PMID- 21877635
TI  - Introduction to carbohydrate counting.
AB  - In the school setting, the school nurse facilitates and coordinates the team that
      implements the nutritional plan for students with diabetes. It is important that
      the school nurse is familiar with basic principles of medical nutrition therapy,
      glucose metabolism, carbohydrate counting, and insulin coverage for meals.

PMID- 21877636
TI  - Chronic care, chronic I.T. problems.

PMID- 21877637
TI  - Unraveling data breaches.

PMID- 21877638
TI  - Making the most of patient safety I.T.

PMID- 21877639
TI  - Finding the leader.

PMID- 21877640
TI  - Health care in the cloud.

PMID- 21877641
TI  - Mapping the future. Interview by Elizabeth Gardner.

PMID- 21877643
TI  - Time to lead.
AB  - Presenters from AHIMA's 2011 Leadership Academy share their perspectives on what
      it takes to lead in the current changing healthcare environment.

PMID- 21877642
TI  - Professional development: how to get started, how to keep growing.
AB  - Professional development is a must for HIM professionals who want to keep on top
      of changes in the healthcare industry. Multiple venues provide professional
      development opportunities for those looking to grow their careers.

PMID- 21877644
TI  - The project management plus: project management skills create opportunities for
      HIM professionals.
AB  - Adding a project management credential to their professional arsenal opens HIM
      professionals to new opportunities both within their facilities and in a range of
      nonprovider settings.

PMID- 21877645
TI  - Opportunity knocks: first jobs offer first opportunities to gain experience and
      confidence.

PMID- 21877646
TI  - Being mindful of change: a technique to reduce stress amid change.
AB  - HIM professionals need more than tools to manage information, they need tools to
      help manage the stress and anxiety a state of constant change can bring.
      "Mindfulness" offers a way to reduce anxiety and keep focused.

PMID- 21877647
TI  - Clear road ahead: no dead-end jobs in this coding department.
AB  - A coding department reorganizes its career paths from the bottom up, creating a
      culture of professional development.

PMID- 21877648
TI  - HIM functions in healthcare quality and patient safety.

PMID- 21877649
TI  - A long goodbye to a great year.

PMID- 21877650
TI  - The power of commitment.

PMID- 21877651
TI  - Patient record regulation.

PMID- 21877652
TI  - 2011's NJ Give Kids a Smile! Is 2nd largest in America.

PMID- 21877653
TI  - Oral Pathology Quiz #71. Case number 1. Squamous cell carcinoma.

PMID- 21877654
TI  - Oral Pathology Quiz #71. Case number 2. Verrucous leukoplakia.

PMID- 21877655
TI  - Orthodontic therapy: a major contributor of iatrogenic induced accelerated
      oxidative stress & free radical dissemination.

PMID- 21877656
TI  - The molecular biology of cancer. Part 2--Why cancers can outsmart our immune
      systems!

PMID- 21877657
TI  - Creating wise forecasts for nursing: the wise forecast model((c)).

PMID- 21877658
TI  - Providing and approving: what's the difference?
AB  - The American Nurses Credentialing Center Accreditation Program accredits both
      providers and approvers of continuing nursing education. At times, there has been
      confusion about the differences between providers and approvers and the role of
      each. This column explains those differences.

PMID- 21877659
TI  - Breaking news: implementing fun methods for keeping nurses informed.
AB  - This column describes an innovative technique for keeping direct care nurses up
      to-date.

PMID- 21877660
TI  - Photo elicitation: enhancing learning in the affective domain.
AB  - This column offers tips for using photo essays in both traditional and online
      learning settings.

PMID- 21877661
TI  - Evaluation of a workplace bullying cognitive rehearsal program in a hospital
      setting.
AB  - Workplace bullying is a serious problem faced by nurses nationally. This study
      was conducted to determine the frequency of workplace bullying and evaluate the
      effectiveness of a training program on cognitive rehearsal of responses to common
      bullying behaviors. This program to increase staff nurses' knowledge of
      management of workplace bullying consisted of three components: pilot survey
      testing, a piloted Internet-based survey administered to the medical and surgical
      nurses, and a 2-hour cognitive rehearsal training program on management of
      workplace bullying. The results showed that 80% of the nurses surveyed had
      experienced workplace bullying over the previous year. After the training
      program, nurses' knowledge of workplace bullying management significantly
      increased. Additionally, nurses were significantly more likely to report that
      they had observed bullying and had bullied others. Further, nurses felt more
      adequately prepared to handle workplace bullying. Results of the research support
      the provision of a workplace bullying management program for nurses and the need
      for a specific policy on workplace bullying.

PMID- 21877664
TI  - Marching in a circle.
AB  - Throughout our history, the United States has come to the rescue of many
      countries under siege from wars, national disasters, and overt poverty. At this
      time in our history, it is our older adult community that is a facing a threat to
      its general welfare. A growing older adult population, increasing longevity with
      accompanying frailty, depleted governmental resources, and minimal
      Medicare/Medicaid payments to providers necessitates a call to leadership,
      innovation, and mutual self-interest. Unless appropriate, needs-based,
      pragmatically funded programs are initiated, our nation will suffer the
      consequences of ignoring a potential health care problem. Postponing action will
      be equated to marching in a circle without any direction.

PMID- 21877669
TI  - Occupational reproductive health and pregnancy hazards confronting health care
      workers.

PMID- 21877670
TI  - Effects of a worksite physical activity intervention for hospital nurses who are
      working mothers.
AB  - Hospital nurses who are working mothers are challenged to maintain their personal
      health and model healthy behaviors for their children. This study aimed to
      develop and test an innovative 10-week worksite physical activity intervention
      integrated into the work flow of hospital-based nurses who were mothers. Three
      volunteer adult medical-surgical nursing units participated as intervention
      units. Fifty-eight nurses (30 intervention and 28 control) provided baseline and
      post-intervention repeated measurements of physical activity (steps) and body
      composition. Intervention participants provided post-intervention focus group
      feedback. For both groups, daily steps averaged more than 12,400 at baseline and
      post-intervention. No significant effects were found for physical activity;
      significant effects were found for fat mass, fat index, and percent fat (p <
      .03). Focus group findings supported the intervention and other data collected.
      The worksite holds promise for targeting the health of working mothers. Future
      research is warranted with a larger sample, longer intervention, and additional
      measures.

PMID- 21877671
TI  - Evaluation of an occupational health nursing program through competency
      achievement: on-campus and distance education, 2005 and 2008.
AB  - This descriptive cross-sectional study was conducted in 2005 and 2008 to evaluate
      self-reported competency achievement by occupational health nursing program
      graduates. Twelve competencies were evaluated at three levels: competent,
      proficient, and expert. In 2005, most graduates believed they were at the
      proficient level in 10 of the 12 competencies, with three competencies
      approaching the expert level. In 2008, all graduates rated their competency
      achievement at the proficient level for all 12 competencies, with nine
      competencies approaching the expert level. Graduates entering the program with
      experience had higher competency scores compared to those without experience.
      Distance education learners had higher competency scores compared to on-campus
      graduates. From 2005 to 2008, reported competency achievement increased in all
      areas except research, which was only marginally reduced by a 0.1 score. Based on
      competency findings, curriculum and course assignments related to leadership
      role, policy development, professional development, and research were modified.

PMID- 21877672
TI  - Promoting occupational health nursing training: an educational outreach with a
      blended model of distance and traditional learning approaches.
AB  - In 2009, occupational health nursing faculty and professionals at the University
      of Washington developed an innovative continuing nursing education offering, the
      OHN Institute. The OHN Institute was designed to meet the following objectives:
      (1) extend basic occupational health nursing training to non-occupational health
      nurses in Federal Region X, (2) target new occupational health nurses or those
      who possessed little or no advanced education in occupational health nursing, and
      (3) offer a hybrid continuing nursing education program consisting of on-site and
      distance learning modalities. Evaluation findings suggested that the various
      continuing nursing education modalities and formats (e.g., asynchronous vs.
      synchronous, online modules vs. live modules) were essentially comparable in
      terms of effectiveness. Perhaps most importantly, the OHN Institute evaluation
      demonstrated that quality continuing nursing education outcomes for occupational
      health nurses depended largely on knowledgeable and engaging faculty and a
      compelling vision of desired outcomes, including the application of learned
      content to professional practice.

PMID- 21877674
TI  - Trenching and excavation-preventing workplace fatalities.

PMID- 21877675
TI  - The potential cost-effectiveness of amblyopia screening programs.
AB  - PURPOSE: To estimate the incremental cost-effective-ness of amblyopia screening
      at preschool and kindergarten, the costs and benefits of three amblyopia
      screening scenarios were compared to no screening and to each other: (1)
      acuity/stereopsis (A/S) screening at kindergarten, (2) A/S screening at preschool
      and kindergarten, and (3) photoscreening at preschool and A/S screening at
      kindergarten. METHODS: A probabilistic microsimulation model of amblyopia natural
      history and response to treatment with screening costs and outcomes estimated
      from two state programs was programmed. The probability was calculated that no
      screening and each of the three interventions were most cost-effective per
      incremental quality-adjusted life year (QALY) gained and case avoided. RESULTS:
      Assuming a minimal 0.01 utility loss from monocular vision loss, no screening was
      most cost-effective with a willingness to pay (WTP) of less than $16,000 per QALY
      gained. A/S screening at kindergarten alone was most cost-effective at a WTP
      between $17,000 and $21,000. A/S screening at preschool and kindergarten was most
      cost-effective at a WTP between $22,000 and $75,000, and photoscreening at
      preschool and A/S screening at kindergarten was most cost-effective at a WTP
      greater than $75,000. Cost-effectiveness substantially improved when assuming a
      greater utility loss. All scenarios were cost-effective when assuming a WTP of
      $10,500 per case of amblyopia cured. CONCLUSION: All three screening
      interventions evaluated are likely to be considered cost-effective relative to
      many other potential public health programs. The choice of screening option
      depends on budgetary resources and the value placed on monocular vision loss
      prevention by funding agencies.

PMID- 21877676
TI  - Surgical management of pediatric limbal dermoids with sutureless amniotic
      membrane transplantation and augmentation.
AB  - PURPOSE: To further evaluate the efficacy of a new surgical technique for removal
      of pediatric corneal-limbal dermoids and ocular surface reconstruction using
      multilayered amniotic membrane. METHODS: Three pediatric patients with corneal
      limbal dermoid (grade I) in one practice were identified in a retrospective
      fashion. All patients underwent deep lamellar excision followed by sutureless
      multilayered amniotic membrane transplantation by a single surgeon (AP).
      Preoperative and postoperative visual acuity, anterior segment examination,
      anterior segment B-scan, and cycloplegic refraction were performed. RESULTS:
      Three patients with ages ranging from 6 months to 18 years had a postoperative
      follow-up of 9 to 12 months from the time of surgery. This surgical technique
      achieved rapid postoperative corneal re-epithelialization, reduced postoperative
      pain, and diminished postoperative scarring in all three patients. Existing
      preoperative astigmatism remained unchanged throughout the follow-up period. No
      intraoperative or postoperative complications were noted. CONCLUSION: This
      surgical approach offers an alternative surgical technique to a simple excision
      with or without deep lamellar keratoplasty for removal of pediatric corneal
      limbal dermoids (grade I). In the management of pediatric limbal dermoids (grade
      I), surgical excision combined with sutureless multilayered amniotic membrane
      transplantation eliminates painful postoperative recovery and corneal
      neovascularization, and can achieve an improved long-term ocular surface
      cosmesis.

PMID- 21877677
TI  - Effect of femtosecond laser cataract surgery on the macula.
AB  - PURPOSE: To compare the effect of conventional and femtosecond laser-assisted
      (Alcon LenSx Inc) phacoemulsification on the macula using optical coherence
      tomography (OCT). METHODS: Twenty eyes of 20 patients underwent uneventful
      cataract surgery in both study groups: femtosecond laser-assisted (laser group)
      and conventional phacoemulsification (control group). Macular thickness and
      volume were evaluated by OCT preoperatively and 1 week and 1 month
      postoperatively. Primary outcomes were OCT retinal thickness in 3 macular areas
      and total macular volume at 1 week and 1 month postoperative. Secondary outcomes
      were changes in retinal thickness at 1 week and 1 month postoperatively, with
      respect to preoperative retinal thickness values and effective
      phacoemulsification time. RESULTS: Multivariable modeling of the effect of
      surgery on postoperative macular thickness showed significantly lower macular
      thickness in the inner retinal ring in the laser group after adjusting for age
      and preoperative thickness across the time course (P=.002). In the control group,
      the inner macular ring was significantly thicker at 1 week (mean: 21.68 MUm; 95%
      confidence limit [CL]: 11.93-31.44 MUm, P<.001). After 1 month, this difference
      decreased to a mean of 17.56 MUm (95% CL: -3.21-38.32 MUm, P=.09) and became
      marginally significant. CONCLUSIONS: Results of this study suggest that
      femtosecond laser-assisted cataract extraction does not differ in postoperative
      macular thickness as compared with standard ultrasound phacoemulsification.

PMID- 21877678
TI  - Mechanical versus alcohol-assisted epithelial debridement during photorefractive
      keratectomy: a confocal microscopic clinical trial.
AB  - PURPOSE: To compare the effects of mechanical versus alcohol-assisted epithelial
      debridement on corneal cellular elements after photorefractive keratectomy (PRK)
      using confocal microscopy. METHODS: This randomized, clinical trial included 66
      eyes from 33 patients with spherical equivalent refraction <-4.00 diopters (D).
      Mechanical versus alcohol-assisted epithelial debridement was performed during
      PRK. The right eye of each patient was randomly assigned to one group (mechanical
      group or alcohol-assisted group) and the fellow eye to the alternate group.
      Confocal examination was performed preoperatively and at 3 and 6 months
      postoperatively. Main outcome measures were keratocyte density and maximum
      anterior stromal light reflectivity. RESULTS: Mean epithelial healing time was
      3.2 +/- 0.4 and 3.0 +/- 0.3 days in the mechanical and alcohol-assisted groups,
      respectively (P=.001). Anterior retroablation stromal keratocyte density was
      704.3 +/- 119.9 cells/mm2 and 734.3 +/- 103.7 cells/mm2 at 3 months (P=.05) and
      643.8 +/- 134.4 cells/mm2 and 696.7 +/- 129.6 cells/mm2 at 6 months (P=.02) in
      the mechanical and alcohol-assisted groups, respectively. No significant
      difference was noted in midstromal and posterior keratocyte density between the
      two groups. Maximum reflectivity was 61.56 +/- 12.64 international units (IU) and
      56.93 +/- 7.86 IU in the mechanical and alcohol-assisted groups, respectively, 3
      months after surgery (P=.018). Corresponding values were 49.46 +/- 4.97 IU and
      48.98 +/- 4.60 IU, respectively, 6 months after surgery (P=.628). CONCLUSIONS:
      Due to more adverse effects of mechanical epithelial debridement on anterior
      keratocyte density and anterior stromal reflectivity, alcohol-assisted epithelial
      debridement is recommended as the procedure of choice for epithelial removal
      during PRK in patients with mild myopia.

PMID- 21877679
TI  - Visual performance of an apodized diffractive multifocal intraocular lens with
      +3.00-d addition: 1-year follow-up.
AB  - PURPOSE: To determine whether implantation of a multifocal intraocular lens (IOL)
      with a lower addition (+3.00 diopters [D]) at the lens plane results in better
      intermediate visual acuity 1 year after surgery compared with a multifocal IOL
      with higher addition (+4.00 D). METHODS: This prospective, randomized, double
      masked study included 80 eyes from 40 patients. Twenty patients were implanted
      bilaterally with the ReSTOR +3.00-D add IOL and 20 patients were implanted
      bilaterally with the ReSTOR +4.00-D add IOL. Primary outcome measures were
      distance, intermediate, and near visual acuity. Secondary outcomes were defocus
      curves, best reading distance, mesopic and photopic contrast sensitivity, quality
      of life, and spectacle independence. Monocular and binocular visual acuity were
      measured as uncorrected and corrected distance visual acuity at 4 m, uncorrected
      near and distance-corrected near visual acuity at 40 cm, and uncorrected
      intermediate visual acuity and distance-corrected intermediate visual acuity at
      50, 60, and 70 cm. RESULTS: Twelve months postoperatively, no statistically
      significant difference between groups in distance and near visual acuity was
      noted. The ReSTOR +3.00-D add group performed better than the ReSTOR +4.00-D add
      group at all intermediate distances studied. The ReSTOR +4.00-D group chose a
      reading distance 8 cm closer than the +3.00-D group. Both groups performed
      similarly with respect to contrast sensitivity, quality of life, and spectacle
      independence rates. CONCLUSIONS: Patients implanted with a multifocal IOL with
      lower addition (ReSTOR +3.00 D) had better performance at intermediate distances
      compared with the ReSTOR +4.00-D add IOL with similar performance for distance
      and near visual acuity, contrast sensitivity, and quality of life.

PMID- 21877680
TI  - Macular detachment for treatment of persistent macular hole.
AB  - The authors report a technique for treatment of persistent macular holes in cases
      refractory to traditional surgical techniques. With a standard pars plana
      vitrectomy approach, subretinal infusion of balanced salt solution was performed
      and followed by a fluid-air exchange. This intervention resulted in hole closure
      despite poor prognosis and may be considered as a treatment option for patients
      with persistent flat macular holes.

PMID- 21877681
TI  - Spontaneous resolution of macular fold following retinal reattachment:
      morphologic features on SD-OCT.
AB  - Macular fold is an infrequent complication after retinal detachment surgery. In
      this report, long-term changes of macular fold are demonstrated using spectral
      domain optical coherence tomography. Although spontaneous resolution was noted in
      this study, spectral-domain optical coherence tomography revealed morphologic
      changes in the photoreceptor layer after resolution of macular fold,
      hyperreflective photoreceptor outer segment, and distorted Henle's fiber layer,
      which might be associated with poor visual outcome even after resolution of the
      fold.

PMID- 21877683
TI  - Shape- and size-controlled synthesis in hard templates: sophisticated chemical
      reduction for mesoporous monocrystalline platinum nanoparticles.
AB  - Here we report a novel hard-templating strategy for the synthesis of mesoporous
      monocrystalline Pt nanoparticles (NPs) with uniform shapes and sizes. Mesoporous
      Pt NPs were successfully prepared through controlled chemical reduction using
      ascorbic acid by employing 3D bicontinuous mesoporous silica (KIT-6) and 2D
      mesoporous silica (SBA-15) as a hard template. The particle size could be
      controlled by changing the reduction time. Interestingly, the Pt replicas
      prepared from KIT-6 showed polyhedral morphology. The single crystallinity of the
      Pt fcc structure coherently extended over the whole particle.

PMID- 21877684
TI  - Anticounterfeit protection of pharmaceutical products with spatial mapping of X
      ray-detectable barcodes and logos.
AB  - Counterfeit pharmaceutical products are a global threat to public health, and
      they undermine the credibility and the financial success of the producers of
      genuine products. The escalating circulation of counterfeit drugs demands new
      anticounterfeit measures that permit rapid screening, are nondestructive, and
      cannot be circumvented easily. Herein we describe a micro-X-ray diffraction (MU
      XRD) protocol for this purpose capable of reading barcodes and logos fabricated
      on various substrates using soft-lithography stamping of compounds that can be
      read by X-ray diffraction but are invisible to the naked eye or optical
      microscopy. This method is demonstrated with barcodes and logos of compounds,
      approved by the Food and Drug Administration, printed on flat substrates as well
      as commercial aspirin and ibuprofen tablets. The MU-XRD protocol is
      nondestructive, automated, and user-friendly and can be used to certify the
      authenticity of drug tablets by mapping hidden patterns printed under the tablet
      coating and on packages.

PMID- 21877685
TI  - A solid lithium electrolyte via addition of lithium isopropoxide to a metal
      organic framework with open metal sites.
AB  - The uptake of LiO(i)Pr in Mg(2)(dobdc) (dobdc(4-) = 1,4-dioxido-2,5
      benzenedicarboxylate) followed by soaking in a typical electrolyte solution leads
      to the new solid lithium electrolyte Mg(2)(dobdc).0.35LiO(i)Pr.0.25LiBF(4).EC.DEC
      (EC = ethylene carbonate; DEC = diethyl carbonate). Two-point ac impedance data
      show a pressed pellet of this material to have a conductivity of 3.1 * 10(-4)
      S/cm at 300 K. In addition, the results from variable-temperature measurements
      reveal an activation energy of just 0.15 eV, while single-particle data suggest
      that intraparticle transport dominates conduction.

PMID- 21877686
TI  - A prebiotic role for 8-oxoguanosine as a flavin mimic in pyrimidine dimer
      photorepair.
AB  - Redox-active enzyme cofactors derived from ribonucleotides have been called
      "fossils of the RNA world," suggesting that early catalysts employed modified
      nucleobases to facilitate redox chemistry in primitive metabolism. Here, we show
      that the common oxidative damage product 8-oxo-7,8-dihydroguanine (OG), when
      incorporated into a DNA or RNA strand in proximity to a cyclobutane pyrimidine
      dimer, can mimic the function of a flavin in photorepair. The OG nucleotide acts
      catalytically in a mechanism consistent with that of photolyase in which the
      photoexcited state of the purine donates an electron to a pyrimidine dimer to
      initiate bond cleavage; subsequent back electron transfer regenerates OG. This
      unusual example of one form of DNA damage, oxidation, functioning to repair
      another, photodimerization, may provide insight into the origins of prebiotic
      redox processes.

PMID- 21877688
TI  - Mitchellenes A-E, cyclic sesquiterpenes from the Australian plant Eremophila
      mitchellii.
AB  - Chemical investigations of the Australian plant Eremophila mitchellii resulted in
      the isolation of the novel tetracyclic sesquiterpene lactones mitchellenes A-C (1
      3), the new sesquiterpene acids mitchellenes D and E (4 and 5), and the
      previously reported natural products 14-hydroxy-6,12-muuroloadien-15-oic acid
      (6), casticin, and centaureidin. The chemical structures of all compounds were
      determined by extensive 1D/2D NMR and MS data analysis. Mitchellenes A-C are the
      first tetracyclic sesquiterpene lactones to be reported; a biosynthetic pathway
      is proposed for these unique secondary metabolites.

PMID- 21877687
TI  - Regiospecific, enantiospecific total synthesis of C-19 methyl substituted
      sarpagine alkaloids dihydroperaksine-17-al and dihydroperaksine.
AB  - The optically active tetracyclic ketone 8 was converted into the pentacylic core
      14 of the C-19 methyl substituted N(a)-H sarpagine and ajmaline alkaloids via a
      critical haloboration reaction. The ketone 14 was then employed in the total
      synthesis of 19(S),20(R)-dihydroperaksine-17-al (1) and 19(S),20(R)
      dihydroperaksine (2). The key regioselective hydroboration and controlled
      oxidation-epimerization sequence developed in this approach should provide a
      general method to functionalize the C(20)-C(21) double bond in the ajmaline
      related indole alkaloids.

PMID- 21877690
TI  - Plasmin substrate binding site cooperativity guides the design of potent peptide
      aldehyde inhibitors.
AB  - Perioperative bleeding is a cause of major blood loss and is associated with
      increased rates of postoperative morbidity and mortality. To combat this,
      antifibrinolytic inhibitors of the serine protease plasmin are commonly used to
      reduce bleeding during surgery. The most effective and previously widely used of
      these is the broad range serine protease inhibitor aprotinin. However, adverse
      clinical outcomes have led to use of alternative serine lysine analogues to
      inhibit plasmin. These compounds suffer from low selectivity and binding
      affinity. Consequently, a concerted effort to discover potent and selective
      plasmin inhibitors has developed. This study used a noncombinatorial peptide
      library to define plasmin's extended substrate specificity and guide the design
      of potent transition state analogue inhibitors. The various substrate binding
      sites of plasmin were found to exhibit a higher degree of cooperativity than had
      previously been appreciated. Peptide sequences capitalizing on these features
      produced high-affinity inhibitors of plasmin. The most potent of these, Lys
      Met(sulfone)-Tyr-Arg-H [KM(O(2))YR-H], inhibited plasmin with a K(i) of 3.1 nM
      while maintaining 25-fold selectivity over plasma kallikrein. Furthermore, 125 nM
      (0.16 MUg/mL) KM(O(2))YR-H attenuated fibrinolysis in vitro with an efficacy
      similar to that of 15 nM (0.20 MUg/mL) aprotinin. To date, this is the most
      potent peptide inhibitor of plasmin that exhibits selectivity against plasma
      kallikrein, making this compound an attractive candidate for further therapeutic
      development.

PMID- 21877689
TI  - Transport kinetics and selectivity of HpUreI, the urea channel from Helicobacter
      pylori.
AB  - Helicobacter pylori's unique ability to colonize and survive in the acidic
      environment of the stomach is critically dependent on uptake of urea through the
      urea channel, HpUreI. Hence, HpUreI may represent a promising target for the
      development of specific drugs against this human pathogen. To obtain insight into
      the structure-function relationship of this channel, we developed conditions for
      the high-yield expression and purification of stable recombinant HpUreI.
      Detergent-solubilized HpUreI forms a homotrimer, as determined by chemical cross
      linking. Urea dissociation kinetics of purified HpUreI were determined by means
      of the scintillation proximity assay, whereas urea efflux was measured in HpUreI
      containing proteoliposomes using stopped-flow spectrometry to determine the
      kinetics and selectivity of the urea channel. The kinetic analyses revealed that
      urea conduction in HpUreI is pH-sensitive and saturable with a half-saturation
      concentration (or K(0.5)) of ~163 mM. The extent of binding of urea by HpUreI was
      increased at lower pH; however, the apparent affinity of urea binding (~150 mM)
      was not significantly pH-dependent. The solute selectivity analysis indicated
      that HpUreI is highly selective for urea and hydroxyurea. Removing either amino
      group of urea molecules diminishes their permeability through HpUreI. Similar to
      urea conduction, diffusion of water through HpUreI is pH-dependent with low water
      permeability at neutral pH.

PMID- 21877691
TI  - Role of a mutated residue at the entrance of the substrate access channel in
      cytochrome p450 engineered for vitamin D(3) hydroxylation activity.
AB  - The cytochrome P450 enzyme engineered for enhancement of vitamin D(3) (VD(3))
      hydroxylation activity, Vdh-K1, includes four mutations (T70R, V156L, E216M, and
      E384R) compared to the wild-type enzyme. Plausible roles for V156L, E216M, and
      E384R have been suggested by crystal structure analysis (Protein Data Bank  3A50
      ), but the role of T70R, which is located at the entrance of the substrate access
      channel, remained unclear. In this study, the role of the T70R mutation was
      investigated by using computational approaches. Molecular dynamics (MD)
      simulations and steered molecular dynamics (SMD) simulations were performed, and
      differences between R70 and T70 were compared in terms of structural change,
      binding free energy change (PMF), and interaction force between the enzyme and
      substrate. MD simulations revealed that R70 forms a salt bridge with D42 and the
      salt bridge affects the locations and the conformations of VD(3) in the bound
      state. SMD simulations revealed that the salt bridge tends to be formed strongly
      when VD(3) passes through the binding pocket. PMFs showed that the T70R mutation
      leads to energetic stabilization of enzyme-VD(3) binding in the region near the
      heme active site. Interestingly, these results concluded that the D42-R70 salt
      bridge at the entrance of the substrate access channel affects the region near
      the heme active site where the hydroxylation of VD(3) occurs; i.e., it is thought
      that the T70R mutation plays an important role in enhancing VD(3) hydroxylation
      activity. A significant future challenge is to compare the hydroxylation
      activities of R70 and T70 directly by a quantum chemical calculation, and three
      dimensional coordinates of the enzyme and VD(3) obtained from MD and SMD
      simulations will be available for the future challenge.

PMID- 21877692
TI  - Rescuing a dysfunctional homologue of a yeast glycyl-tRNA synthetase gene.
AB  - The yeast Saccharomyces cerevisiae contains two distinct nuclear glycyl-tRNA
      synthetase (GlyRS) genes, GRS1 and GRS2. GRS1 is dual functional in that
      possesses both cytoplasmic and mitochondrial activities, whereas GRS2 is
      pseudogene-like. GlyRS1 and GlyRS2 are highly similar on the whole but are
      distinguished by a lysine-rich insertion domain of 44 amino acid residues,
      present only in GlyRS1. We herein present evidence that whereas the insertion
      domain is dispensable for the complementary activity of GRS1in vivo, deletion of
      this domain from GlyRS1 reduced its aminoacylation activity by up to 9-fold. On
      the other hand, fusion of a constitutive ADH promoter to GRS2 failed to confer a
      functional phenotype to the gene, but further fusion of ARC1 (a yeast gene
      encoding a tRNA-binding protein, Arc1p) to this hybrid gene successfully rescued
      its activity. Most intriguingly, purified GlyRS2 retained a substantial level of
      aminoacylation activity. Fusion of Arc1p to this enzyme further enhanced its
      activity and stability. These findings highlight not only the structural
      integrity of the pseudogene-encoded enzyme but also the necessity of obtaining an
      auxiliary tRNA-binding domain for functioning of a yeast tRNA synthetase.

PMID- 21877693
TI  - Fabrication of spiropyran-containing thin film sensors used for the simultaneous
      identification of multiple metal ions.
AB  - In this article, a methacrylate-based spiropyran-containing copolymer was used as
      a colorimetric sensor to identify multiple metal ions simultaneously. Through UV
      vis absorption spectroscopy, the relative binding affinity of merocyanine to each
      metal ion was investigated by displacement studies of a bound metal ion with a
      second metal ion of a higher binding affinity. We also show that because each
      metal ion gives rise to a distinct spectral response, partial least-squares
      discriminant analysis (PLS-DA) can be used to analyze the UV-vis absorbance
      spectra to identify the two metal ions that are present in solution at varying
      concentrations simply by dipping a coated polymer substrate into solution after
      irradiation. Partial least-squares regression analysis (PLS) was used to
      determine the metal ions in solution for several binary mixtures quantitatively.
      We also demonstrate that the quantitative determination depends on the relative
      binding preference of merocyanine to each metal ion.

PMID- 21877694
TI  - Improved solvent extraction procedure and high-performance liquid chromatography
      evaporative light-scattering detector method for analysis of polar lipids from
      dairy materials.
AB  - A normal-phase high-performance liquid chromatography-evaporative light
      scattering detector method employing dichloromethane, methanol, and acetic
      acid/triethylamine buffer as the mobile phase was developed for analysis of polar
      lipids (PLs). This method was applicable for analysis of PLs from both dairy
      materials and soy lecithin. All of the PLs of interest such as glycolipids,
      phospholipids, and sphingomyelin were well separated with a total run time of
      22.5 min and without necessitating the removal of neutral lipids beforehand. Peak
      retention times were stable, and the method was reproducible. In this study, a
      modified method of using solvents for extraction of PLs from dairy matrices was
      also investigated. The modified method offered higher extraction efficiency,
      consumed less time, and in some cases saved solvent use.

PMID- 21877695
TI  - Dechlorination of trichloroethene in a continuous-flow bioelectrochemical
      reactor: effect of cathode potential on rate, selectivity, and electron transfer
      mechanisms.
AB  - The exciting discovery that dechlorinating bacteria can use polarized graphite
      cathodes as direct electron donors in the reductive dechlorination has prompted
      investigations on the development of novel bioelectrochemical remediation
      approaches. In this work, we investigated the performance of a bioelectrochemical
      reactor for the treatment of trichloroethene (TCE). The reactor was continuously
      operated for about 570 days, at different potentiostatically controlled cathode
      potentials, ranging from -250 mV to -750 mV vs standard hydrogen electrode. The
      rate and extent of TCE dechlorination, as well as the competition for the
      available electrons, were highly dependent on the set cathode potential. When the
      cathode was controlled at -250 mV, no abiotic hydrogen production occurred and
      TCE dechlorination (predominantly to cis-DCE and VC), most probably sustained via
      direct extracellular electron transfer, proceeded at an average rate of 15.5 +/-
      1.2 MUmol e(-)/L d. At this cathode, potential methanogenesis was almost
      completely suppressed and dechlorination accounted for 94.7 +/- 0.1% of the
      electric current (15.0 +/- 0.8 MUA) flowing in the system. A higher rate of TCE
      dechlorination (up to 64 +/- 2 MUmol e(-)/L d) was achieved at cathode potentials
      lower than -450 mV, though in the presence of a very active methanogenesis which
      accounted for over 60% of the electric current. Remarkably, the
      bioelectrochemical reactor displayed a stable and reproducible performance even
      without the supply of organic carbon sources with the feed, confirming long-term
      viability.

PMID- 21877696
TI  - Phase characterization and study of molecular order of a three-ring mesogen by
      13C NMR in smectic C and nematic phases.
AB  - Molecules exhibiting a thermotropic liquid-crystalline property have acquired
      significant importance due to their sensitivity to external stimuli such as
      temperature, mechanical forces, and electric and magnetic fields. As a result,
      several novel mesogens have been synthesized by the introduction of various
      functional groups in the vicinity of the aromatic core as well as in the side
      chains and their properties have been studied. In the present study, we report
      three-ring mesogens with hydroxyl groups at one terminal. These mesogens were
      synthesized by a multistep route, and structural characterization was
      accomplished by spectral techniques. The mesophase properties were studied by hot
      stage optical polarizing microscopy, differential scanning calorimetry, and small
      angle X-ray scattering. An enantiotropic nematic phase was noticed for lower
      homologues, while an additional smectic C phase was found for higher homologues.
      Solid-state high-resolution natural abundance (13)C NMR studies of a typical
      mesogen in the solid phase and in the mesophases have been carried out. The (13)C
      NMR spectrum of the mesogen in the smectic C and nematic phases indicated
      spontaneous alignment of the molecule in the magnetic field. By utilizing the two
      dimensional separated local field (SLF) NMR experiment known as SAMPI4, (13)C
      (1)H dipolar couplings have been obtained, which were utilized to determine the
      orientational order parameters of the mesogen.

PMID- 21877697
TI  - Palladium-based plasmonic perfect absorber in the visible wavelength range and
      its application to hydrogen sensing.
AB  - We report on the experimental realization of a palladium-based plasmonic perfect
      absorber at visible wavelengths and its application to hydrogen sensing. Our
      design exhibits a reflectance <0.5% and zero transmittance at 650 nm and the
      operation wavelength of the absorber can be tuned by varying its structural
      parameters. Exposure to hydrogen gas causes a rapid and reversible increase in
      reflectance on a time scale of seconds. This pronounced response introduces a
      novel optical hydrogen detection scheme with very high values of the relative
      intensity response.

PMID- 21877698
TI  - Poly(pyrazolyl)aluminate complexes containing aluminum-hydrogen bonds.
AB  - The treatment of LiAlH(4) with 2, 3, or 4 equiv of the 3,5-disubstituted
      pyrazoles Ph(2)pzH or iPr(2)pzH afforded [Li(THF)(2)][AlH(2)(Ph(2)pz)(2)] (97%),
      [Li(THF)][AlH(Ph(2)pz)(3)] (96%), [Li(THF)(4)][Al(Ph(2)pz)(4)] (95%), and
      [Li(THF)][AlH(iPr(2)pz)(3)] (89%). The treatment of ZnCl(2) with
      [Li(THF)][AlH(Ph(2)pz)(3)] afforded Zn(AlH(Ph(2)Pz)(3))H (70%). X-ray crystal
      structures of these complexes demonstrated kappa(2) or kappa(3) coordination of
      the aluminum-based ligands to the Li or Zn ions. The treatment of
      [Li(THF)][AlH(Ph(2)pz)(3)] with MgBr(2) or CoCl(2) in THF/Et(2)O solutions, by
      contrast, afforded the pyrazolate transfer products
      Mg(2)Br(2)(Ph(2)pz)(2)(THF)(3).2THF (25%) and Co(2)Cl(2)(Ph(2)pz)(2)(THF)(3).THF
      (23%) as colorless and blue crystalline solids, respectively. An analogous
      treatment of [Li(THF)][AlH(Ph(2)pz)(3)] with MCl(2) (M = Mn, Fe, Ni, Cu) afforded
      metal powders and H(2), illustrating hydride transfer from Al to M as a competing
      reaction path.

PMID- 21877699
TI  - The lithium-thiophene riddle revisited.
AB  - A recent study of the interaction of a lithium atom with the thiophene molecule
      found a large disagreement between high-level coupled cluster (CCSD(T)/AVTZ) and
      quantum Monte Carlo (fixed-node diffusion Monte Carlo, or FNDMC) calculations. We
      address this "lithium-thiophene riddle" by analyzing the influence of crucial
      FNDMC simulation parameters, namely, the one-electron models, basis sets, and
      pseudopotentials used for the generation of the trial wave function. These are
      shown to have a significant impact on the calculated FNDMC interaction energies,
      and good agreement between CCSD(T) and FNDMC is found when nodal hypersurfaces of
      sufficient quality are used. On the basis of our proposed consensus reference
      value, we go on to benchmark the standard toolbox of lower-level quantum
      chemistry methods for this model interaction. Newly developed dispersion
      corrected DFT methods perform reasonably well despite the partial charge transfer
      character of the interaction and might well be worthy of further study in larger
      lithium-thiophene systems.

PMID- 21877700
TI  - Characterization of solvent-extractable organics in urban aerosols based on mass
      spectrum analysis and hygroscopic growth measurement.
AB  - To characterize atmospheric particulate organics with respect to polarity,
      aerosol samples collected on filters in the urban area of Nagoya, Japan, in 2009
      were extracted using water, methanol, and ethyl acetate. The extracts were
      atomized and analyzed using a high-resolution time-of-flight aerosol mass
      spectrometer (HR-ToF-AMS) and a hygroscopicity tandem differential mobility
      analyzer. The atmospheric concentrations of the extracted organics were
      determined using phthalic acid as a reference material. Comparison of the organic
      carbon concentrations measured using a carbon analyzer and the HR-ToF-AMS
      suggests that organics extracted with water (WSOM) and ethyl acetate (EASOM) or
      those extracted with methanol (MSOM) comprise the greater part of total organics.
      The oxygen-carbon ratios (O/C) of the extracted organics varied: 0.51-0.75
      (WSOM), 0.37-0.48 (MSOM), and 0.27-0.33 (EASOM). In the ion-group analysis, WSOM,
      MSOM, and EASOM were clearly characterized by the different fractions of the CH
      and CO(2) groups. On the basis of the hygroscopic growth measurements of the
      extracts, kappa of organics at 90% relative humidity (kappa(org)) were estimated.
      Positive correlation of kappa(org) with O/C (r 0.70) was found for MSOM and
      EASOM, but no clear correlation was found for WSOM.

PMID- 21877701
TI  - Observation of ClNO2 in a mid-continental urban environment.
AB  - In the troposphere, nitryl chloride (ClNO2), produced from uptake of dinitrogen
      pentoxide (N2O5) on chloride containing aerosol, can be an important nocturnal
      reservoir of NO(x) (= NO + NO2) and a source of atomic Cl, particularly in
      polluted coastal environments. Here, we present measurements of ClNO2 mixing
      ratios by chemical ionization mass spectrometry (CIMS) in Calgary, Alberta,
      Canada over a 3-day period. The observed ClNO2 mixing ratios exhibited a strong
      diurnal profile, with nocturnal maxima in the range of 80 to 250 parts-per
      trillion by volume (pptv) and minima below the detection limit of 5 pptv in the
      early afternoon. At night, ClNO2 constituted up to 2% of odd nitrogen, or NO(y).
      The peak mixing ratios of ClNO2 observed were considerably below the modeled
      integrated heterogeneous losses of N2O5, indicating that ClNO2 production was a
      minor pathway compared to heterogeneous hydrolysis of N2O5. Back trajectory
      analysis using HYSPLIT showed that the study region was not influenced by fresh
      injections of marine aerosol, implying that aerosol chloride was derived from
      anthropogenic sources. Molecular chlorine (Cl2), derived from local anthropogenic
      sources, was observed at mixing ratios of up to 65 pptv and possibly contributed
      to formation of aerosol chloride and hence the formation of ClNO2.

PMID- 21877702
TI  - Resonance-mode electrochemical impedance measurements of silicon dioxide
      supported lipid bilayer formation and ion channel mediated charge transport.
AB  - A single-chip electrochemical method based on impedance measurements in resonance
      mode has been employed to study lipid monolayer and bilayer formation on
      hydrophobic alkanethiolate and SiO(2) substrates, respectively. The processes
      were monitored by temporally resolving changes in interfacial capacitance and
      resistance, revealing information about the rate of formation, coverage, and
      defect density (quality) of the layers at saturation. The resonance-based
      impedance measurements were shown to reveal significant differences in the layer
      formation process of bilayers made from (i) positively charged lipid 1-palmitoyl
      2-oleoyl-sn-glycero-3-ethylphosphocholine (POEPC), (ii) neutral lipid 1-palmitoyl
      2-oleoyl-sn-glycero-3-phosphocholine (POPC) on SiO(2), and (iii) monolayers made
      from POEPC on hydrophobic alkanethiolate substrates. The observed responses were
      represented with an equivalent circuit, suggesting that the differences primarily
      originate from the presence of a conductive aqueous layer between the lipid
      bilayers and the SiO(2). In addition, by adding the ion channel gramicidin D to
      bilayers supported on SiO(2), channel-mediated charge transport could be measured
      with high sensitivity (resolution around 1 pA).

PMID- 21877703
TI  - Transverse mixing enhancement due to bacterial random motility in porous
      microfluidic devices.
AB  - Bacterial swimming in groundwater may create flow disturbances in the surrounding
      microenvironment thereby enhancing contaminant mixing. Porous microfluidic
      devices (MFDs) were fabricated in three different pore geometry designs: uniform
      grain size with large pore throats (MFD-I), nonuniform grain size with restricted
      pore space (MFD-II), and uniform grain size with small pore throats (MFD-III). 
      Escherichia coli  HCB33 was used to assess the effect of bacterial random
      motility on transverse mixing of a tracer, fluorescent labeled dextran, under
      three experimental conditions in which motile bacteria, nonmotile bacteria, and
      plain buffer suspensions were flown through the MFDs at four different flow
      rates. Mixing was quantified in terms of the best-fit effective transverse
      dispersion coefficient ((D(cy))(eff)). A mixing enhancement index (MEI) was
      defined as the ratio of the (D(cy))(eff) of tracer in experiments with motile
      bacteria and without bacteria. Motile bacteria caused a maximum 5-6 fold increase
      in MEI in MFD-II, a nearly 4-fold increase in MFD-I, and very little observed
      change in MFD-III. The apparent transverse dispersivities (alpha(app)) of MFD-II
      and MFD-I increased by 3 and 2.3 times, respectively, with no change in MFD-III.
      These observations indicate that both pore throat size and pore arrangement are
      critical factors for contaminant mixing in porous media.

PMID- 21877704
TI  - Development and sensitivity analysis of a fully kinetic model of sequential
      reductive dechlorination in groundwater.
AB  - A fully kinetic biogeochemical model of sequential reductive dechlorination
      (SERD) occurring in conjunction with lactate and propionate fermentation, iron
      reduction, sulfate reduction, and methanogenesis was developed. Production and
      consumption of molecular hydrogen (H(2)) by microorganisms have been modeled
      using modified Michaelis-Menten kinetics and has been implemented in the
      geochemical code PHREEQC. The model have been calibrated using a Shuffled Complex
      Evolution Metropolis algorithm to observations of chlorinated solvents, organic
      acids, and H(2) concentrations in laboratory batch experiments of complete
      trichloroethene (TCE) degradation in natural sediments. Global sensitivity
      analysis was performed using the Morris method and Sobol sensitivity indices to
      identify the most influential model parameters. Results show that the sulfate
      concentration and fermentation kinetics are the most important factors
      influencing SERD. The sensitivity analysis also suggests that it is not possible
      to simplify the model description if all system behaviors are to be well
      described.

PMID- 21877705
TI  - The respiratory syncytial virus transcription antiterminator M(2-1) is a highly
      stable, zinc binding tetramer with strong pH-dependent dissociation and a
      monomeric unfolding intermediate.
AB  - The human respiratory syncytial virus M(2-1) transcription antiterminator is an
      essential elongation factor required by the RNA polymerase for effective
      transcription beyond the first two nonstructural genes. Its exclusive presence in
      pneumovirus among all paramyxovirus suggests a unique function within this small
      genus. With the aim of understanding its biochemical properties, we investigated
      this alpha-helical tetramer by making use of a biophysical approach. We found
      that the tetramer hydrodynamic radius is considerably extended at high ionic
      strengths and determined its zinc content to be one atom per monomer.
      Dissociation-unfolding experiments show a fully reversible and concentration
      dependent cooperative transition, but secondary and tertiary structural changes
      are uncoupled at lower protein concentrations. We detect the presence of a
      monomeric intermediate, which can be classified as a "late molten globule" with
      substantial secondary and tertiary structure. Global fittings of experiments from
      three different probes at two M(2-1) concentrations provide a free energy of
      dissociation-unfolding of -36.8 +/- 0.1 kcal mol(-1), corresponding to a tight
      dissociation constant of 10(-28) M(3) at pH 7.0. The tetramer affinity is
      strongly governed by pH, with a free energy change of 13 kcal mol(-1) when pH
      decreases from 7.0 to 5.0 (K(D) = 10(-18) M(3)). The drastic changes that take
      place within a pH range compatible with a cellular environment strongly suggest a
      regulatory effect of pH on M(2-1) structure and biochemical properties, likely
      affecting transcription and interaction with proteins and RNA.

PMID- 21877706
TI  - Effects of the spaces available for cations in strongly acidic cation-exchange
      resins on the exchange equilibria by quaternary ammonium ions and on the
      hydration states of metal ions.
AB  - The spaces (voids) available for cations in the five exchange resins with varying
      exchange capacities and cross-linking degrees were estimated, on the basis of the
      additivity of molar volumes of the constituents. Tetraalkylammonium ions
      (NR(4)(+); R: Me, Et, Pr) may completely exchange potassium ion on the resin
      having a larger void radius. In contrast, the ratio of saturated adsorption
      capacity to exchange capacity of the resin having a smaller void radius decreased
      with an increase in size of NR(4)(+) ions, due to the interionic contacts. Alkali
      metal ions could be exchanged quantitatively. While the hydration numbers of
      K(+), Rb(+), and Cs(+) were independent of the void radius, those of Li(+) and
      Na(+), especially Na(+), decreased with a decrease in void radius. Interionic
      contacts between the hydrated ions enhance the dehydration. Multivalent metal
      ions have the hydration numbers, comparable to or rather greater than those in
      water. A greater void volume available due to exchange stoichiometry released the
      interionic contacts and occasionally promoted the involvement of water molecules
      other than directly bound molecules. The close proximity between ions in the
      conventional ion-exchange resins having higher exchange capacities may induce
      varying interactions.

PMID- 21877707
TI  - Nickel-catalyzed formation of cyclopentenone derivatives via the unique
      cycloaddition of alpha,beta-unsaturated phenyl esters with alkynes.
AB  - Oxygen-containing organic compounds, such as ethers, carboxylates, and
      carbamates, have recently received increasing attention because of their newly
      discovered applications as electrophiles in cross-coupling reactions via
      transition metal-catalyzed C-O bond activation. However, no cycloaddition
      reaction involving their C-O bond activation has been demonstrated thus far. The
      present study developed a Ni(0)-catalyzed unique [3+2] cycloaddition reaction of
      alpha,beta-unsaturated phenyl esters with alkynes in (i)PrOH to yield
      cyclopentenone derivatives.

PMID- 21877708
TI  - Growth, defect formation, and morphology control of germanium-silicon
      semiconductor nanowire heterostructures.
AB  - By the virtue of the nature of the vapor-liquid-solid (VLS) growth process in
      semiconductor nanowires (NWs) and their small size, the nucleation, propagation,
      and termination of stacking defects in NWs are dramatically different from that
      in thin films. We demonstrate germanium-silicon axial NW heterostructure growth
      by the VLS method with 100% composition modulation and use these structures as a
      platform to understand how defects in stacking sequence force the ledge
      nucleation site to be moved along or pinned at a single point on the triple-phase
      circumference, which in turn determines the NW morphology. Combining structural
      analysis and atomistic simulation of the nucleation and propagation of stacking
      defects, we explain these observations based on preferred nucleation sites during
      NW growth. The stacking defects are found to provide a fingerprint of the layer
      by-layer growth process and reveal how the 19.5 degrees  kinking in semiconductor
      NWs observed at high Si growth rates results from a stacking-induced twin
      boundary formation at the NW edge. This study provides basic foundations for an
      atomic level understanding of crystalline and defective ledge nucleation and
      propagation during [111] oriented NW growth and improves understanding for
      control of fault nucleation and kinking in NWs.

PMID- 21877709
TI  - A concise total synthesis of (-)-maoecrystal Z.
AB  - The first total synthesis of (-)-maoecrystal Z is described. The key steps of the
      synthesis include a diastereoselective Ti(III)-mediated reductive epoxide
      coupling reaction and a diastereoselective Sm(II)-mediated reductive cascade
      cyclization reaction. These transformations enabled the preparation of (-)
      maoecrystal Z in only 12 steps from (-)-gamma-cyclogeraniol.

PMID- 21877711
TI  - Nanosynthesis routes to new tetrahedral crystalline solids: silicon-like Si3AlP.
AB  - We introduce a synthetic strategy to access functional semiconductors with
      general formula A(3)XY (A = IV, X-Y = III-V) representing a new class within the
      long-sought family of group IV/III-V hybrid compounds. The method is based on
      molecular precursors that combine purposely designed polar/nonpolar bonding at
      the nanoscale, potentially allowing precise engineering of structural and optical
      properties, including lattice dimensions and band structure. In this Article, we
      demonstrate the feasibility of the proposed strategy by growing a new
      monocrystalline AlPSi(3) phase on Si substrates via tailored interactions of
      P(SiH(3))(3) and Al atoms using gas source (GS) MBE. In this case, the high
      affinity of Al for the P ligands leads to Si(3)AlP bonding arrangements, which
      then confer their structure and composition to form the corresponding Si(3)AlP
      target solid via complete elimination of H(2) at ~500  degrees C. First principle
      simulations at the molecular and solid-state level confirm that the Si(3)AlP
      building blocks can readily interlink with minimal distortion to produce diamond
      like structures in which the P atoms are arranged on a common sublattice as third
      nearest neighbors in a manner that excludes the formation of unfavorable Al-Al
      bonds. High-resolution XRD, XTEM, and RBS indicate that all films grown on
      Si(100) are tetragonally strained and fully coherent with the substrate and
      possess near-cubic symmetry. The Raman spectra are consistent with a growth
      mechanism that proceeds via full incorporation of preformed Si(3)AlP tetrahedra
      with residual orientational disorder. Collectively, the characterization data
      show that the structuro-chemical compatibility between the epilayer and substrate
      leads to flawless integration, as expected for pseudohomoepitaxy of an Si-like
      material grown on a bulk Si platform.

PMID- 21877710
TI  - A synthetic naringenin derivative, 5-hydroxy-7,4'-diacetyloxyflavanone-N-phenyl
      hydrazone (N101-43), induces apoptosis through up-regulation of Fas/FasL
      expression and inhibition of PI3K/Akt signaling pathways in non-small-cell lung
      cancer cells.
AB  - Naringenin, a well-known naturally occurring flavonone, demonstrates cytotoxicity
      in a variety of human cancer cell lines; its inhibitory effects on tumor growth
      have spurred interest in its therapeutic application. In this study, naringenin
      was derivatized to produce more effective small-molecule inhibitors of cancer
      cell proliferation, and the anticancer effects of its derivative, 5-hydroxy-7,4'
      diacetyloxyflavanone-N-phenyl hydrazone (N101-43), in non-small-cell lung cancer
      (NSCLC) cell lines NCI-H460, A549, and NCI-H1299 were investigated. Naringenin
      itself possesses no cytotoxicity against lung cancer cells. In contrast, N101-43
      inhibits proliferation of both NCI-H460 and A549 cell lines; this capacity is
      lost in p53-lacking NCI-H1299 cells. N101-43 induces apoptosis via sub-G1 cell
      cycle arrest in NCI-H460 and via G0/G1 arrest in A549 cells. Expression of
      apoptosis and cell-cycle regulatory factors is altered: Cyclins A and D1 and
      phospho-pRb are down-regulated, but expression of CDK inhibitors such as p21,
      p27, and p53 is enhanced by N101-43 treatment; N101-43 also increases expression
      levels of the extrinsic death receptor Fas and its binding partner FasL.
      Furthermore, N101-43 treatment diminishes levels of cell survival factors such as
      PI3K and p-Akt dose-dependently, and N101-43 additionally induces cleavage of the
      pro-apoptotic factors caspase-3, caspase-8, and poly ADP-ribose polymerase
      (PARP). Cumulatively, these investigations show that the naringenin derivative
      N101-43 induces apoptosis via up-regulation of Fas/FasL expression, activation of
      caspase cascades, and inhibition of PI3K/Akt survival signaling pathways in NCI
      H460 and A549 cells. In conclusion, these data indicate that N101-43 may have
      potential as an anticancer agent in NSCLC.

PMID- 21877712
TI  - Reactivity and synthesis inspired by the Zincke ring-opening of pyridines.
AB  - The century-old Zincke process for ring-opening of pyridinium salts produces 5
      amino-2,4-pentadienals, a type of donor-acceptor dienes known as Zincke
      aldehydes. Inspired by this reasonably general and often efficient process for
      dearomatization, my laboratory has used pyridines as a starting point for
      heterocycle synthesis, which resulted in unusual syntheses of indoles,
      pyrrolines, and a formal synthesis of the natural product porothramycin A.
      Furthermore, our study of the reactivity of Zincke aldehydes has led to
      accidental discoveries of pericyclic cascade reactions that produce Z-alpha,beta
      unsaturated amides or polycyclic lactams, depending upon the identity of the
      substituents on nitrogen. Finally, a base-mediated formal cycloaddition reaction
      of tryptamine-derived Zincke aldehydes has served as the key step in concise
      syntheses of the indole alkaloids norfluorocurarine and strychnine.

PMID- 21877713
TI  - AADS--an automated active site identification, docking, and scoring protocol for
      protein targets based on physicochemical descriptors.
AB  - We report here a robust automated active site detection, docking, and scoring
      (AADS) protocol for proteins with known structures. The active site finder
      identifies all cavities in a protein and scores them based on the physicochemical
      properties of functional groups lining the cavities in the protein. The accuracy
      realized on 620 proteins with sizes ranging from 100 to 600 amino acids with
      known drug active sites is 100% when the top ten cavity points are considered.
      These top ten cavity points identified are then submitted for an automated
      docking of an input ligand/candidate molecule. The docking protocol uses an all
      atom energy based Monte Carlo method. Eight low energy docked structures
      corresponding to different locations and orientations of the candidate molecule
      are stored at each cavity point giving 80 docked structures overall which are
      then ranked using an effective free energy function and top five structures are
      selected. The predicted structure and energetics of the complexes agree quite
      well with experiment when tested on a data set of 170 protein-ligand complexes
      with known structures and binding affinities. The AADS methodology is implemented
      on an 80 processor cluster and presented as a freely accessible, easy to use tool
      at  http://www.scfbio-iitd.res.in/dock/ActiveSite_new.jsp .

PMID- 21877714
TI  - Matrix infrared spectroscopic and computational studies on the reactions of
      osmium and iron atoms with carbon monoxide and dinitrogen mixtures.
AB  - Reactions of laser-ablated osmium and iron atoms with CO and N(2) mixtures in
      excess neon have been investigated using matrix isolation infrared spectroscopy.
      The (NN)(x)MCO (M = Os, Fe; x = 1, 2) complexes are formed as reaction products
      during sample deposition and on annealing. These reaction products are
      characterized on the basis of the results of isotopic substitution, mixed
      isotopic splitting patterns, stepwise annealing, broad-band irradiation, and
      change of reagent concentration and laser energy. Density functional theory
      calculations have been performed on these products. Overall agreement between the
      experimental and calculated results supports the identification of these species
      from the matrix infrared spectra. The bonding characteristics and reaction
      mechanisms have been discussed. The M-C bonds are stronger than the M-N bonds in
      the same molecules. The formation of metal carbonyl dinitrogen complexes from the
      addition of CO to metal dinitrogen complexes is found to be more energetically
      favorable than that from the reactions of N(2) with metal carbonyls.

PMID- 21877715
TI  - Greenhouse gas emissions from the consumption of electric and electronic
      equipment by Norwegian households.

PMID- 21877716
TI  - Hydration-responsive folding and unfolding in graphene oxide liquid crystal
      phases.
AB  - Graphene oxide is promising as a plate-like giant molecular building block for
      the assembly of new carbon materials. Its water dispersibility, liquid
      crystallinity, and ease of reduction offer advantages over other carbon
      precursors if its fundamental assembly rules can be identified. This article
      shows that graphene oxide sheets of known lateral dimension form nematic liquid
      crystal phases with transition points in agreement with the Onsager hard-plate
      theory. The liquid crystal phases can be systematically ordered into defined
      supramolecular patterns using surface anchoring, complex fluid flow, and
      microconfinement. Graphene oxide is seen to exhibit homeotropic surface anchoring
      at interfaces driven by excluded volume entropy and by adsorption enthalpy
      associated with its partially hydrophobic basal planes. Surprisingly, some of the
      surface-ordered graphene oxide phases dry into graphene oxide solids that undergo
      a dramatic anisotropic swelling upon rehydration to recover their initial size
      and shape. This behavior is shown to be a unique hydration-responsive folding and
      unfolding transition. During drying, surface tension forces acting parallel to
      the layer planes cause a buckling instability that stores elastic energy in
      accordion-folded structures in the dry solid. Subsequent water infiltration
      reduces interlayer frictional forces and triggers release of the stored elastic
      energy in the form of dramatic unidirectional expansion. We explain the
      folding/unfolding phenomena by quantitative nanomechanics and introduce the
      potential of liquid crystal-derived graphene oxide phases as new stimuli-response
      materials.

PMID- 21877717
TI  - Effective fragment potential study of the interaction of DNA bases.
AB  - Hydrogen-bonded and stacked structures of adenine-thymine and guanine-cytosine
      nucleotide base pairs, along with their methylated analogues, are examined with
      the ab inito based general effective fragment potential (EFP2) method. A
      comparison of coupled cluster with single, double, and perturbative triple
      (CCSD(T)) energies is presented, along with an EFP2 energy decomposition to
      illustrate the components of the interaction energy.

PMID- 21877718
TI  - Molecular mechanisms for the induction of peroxidase activity of the cytochrome c
      cardiolipin complex.
AB  - Induction of the peroxidase activity of cytochrome c (cyt c) by cardiolipin (CL)
      and H(2)O(2) in mitochondria is suggested to be a key event in early apoptosis.
      Although electrostatic interaction between the positively charged cyt c and
      negatively charged CL is a predominant force behind the formation of a specific
      cyt c-CL complex and sequential induction of the peroxidase activity, molecular
      mechanisms of hydrophobic interactions involving the fatty acyl chains of CL
      remain to be investigated. To elucidate the function of the acyl chains,
      particularly the role of the double bond, we synthesized a variety of CL
      analogues and examined their peroxidase inducing activity. Irrespective of the
      number of double bonds in the acyl chains, the peroxidase activity of cyt c
      induced by liposomes composed of 1,2-dioleoyl-sn-glycero-3-phosphatidylcholine
      (DOPC) and a different CL (9:1 molar ratio) was similar, except for that of
      1,1',2,2'-tetrastearoylcardiolipin (TSCL, C18:0)-containing liposomes. The
      peroxidase inducing activity of TSCL-containing liposomes was 3-4-fold greater
      than that of other CL-containing liposomes. The peroxidase activity induced by
      all CL-containing liposomes was much lower at high ionic strengths than that at
      low ionic strengths because of diminution of the electrostatic interaction. The
      peroxidase inducing effects of various CL-containing liposomes were related well
      to their ability to associate with cyt c. Thus, our results revealed that at low
      CL levels, the saturated acyl chain of CL is favorable for the activation of
      peroxidase activity of CL-bound cyt c and the proposed critical role of the
      double bond is not a general feature of the cyt c-CL interaction. The polarity of
      the membrane surface of TSCL-containing liposomes was slightly, but
      significantly, lower than that of other CL-containing liposomes, suggesting that
      the higher activating ability of TSCL-containing liposomes may be due to a
      reduced level of hydration of the polar head region reflecting tighter packing of
      the fully saturated acyl chains. Moreover, using CL analogues in which a central
      glycerol head moiety was modified, we revealed that the natural structure of the
      head moiety is not critical for the formation of the active cyt c-CL complex. The
      effects of the CL content of the liposomal membrane on the cyt c-CL interaction
      are discussed.

PMID- 21877719
TI  - "Nanoscale lattice fence" in a metal-organic framework: interplay between hinged
      topology and highly anisotropic thermal response.
AB  - A thermoresponsive, 3D hinged metal-organic framework (HMOF-1) assembled from
      meso-tetra(4-pyridyl)porphine and CdI(2) exhibits a 3D "lattice fence" topology
      with extraordinary thermal expansion and shrinkage. A simple structural model is
      established to elucidate such a drastic thermal response. The hinged structure
      model presented here can also be applied to other "lattice fence" topologies with
      little or no modification, depending on the symmetry of the molecular building
      blocks.

PMID- 21877720
TI  - Photoinduced oxidation of the insecticide phenothrin on soil surfaces.
AB  - Photodegradation profiles of the pyrethroid insecticide phenothrin on a moistened
      U.S. soil thin layer was investigated by using its predominant component, the 1R
      trans-isomer (I), under continuous exposure to light at >290 nm from a xenon arc
      lamp. Its degradation was moderately accelerated by irradiation with half-lives
      of 5.7-5.9 days (dark control 21-24 days), mainly via successive oxidation of the
      2-methylprop-1-enyl group and ester cleavage followed by mineralization to carbon
      dioxide. Spectroscopic and cochromatographic analyses showed that the major
      degradates were the alcohol and ketone derivatives of I formed via photoinduced
      oxidation of the 2-methylprop-1-enyl group by singlet oxygen. The photoinduced
      generation of singlet oxygen in/on the soil surface was confirmed by using
      chemical trapping reactions together with ESR spectroscopy.

PMID- 21877721
TI  - Modeling the chemical step utilized by human alkyladenine DNA glycosylase: a
      concerted mechanism AIDS in selectively excising damaged purines.
AB  - Human alkyladenine DNA glycosylase (AAG) initiates the repair of a wide variety
      of (neutral or cationic) alkylated and deaminated purines by flipping damaged
      nucleotides out of the DNA helix and catalyzing the hydrolytic N-glycosidic bond
      cleavage. Unfortunately, the limited number of studies on the catalytic pathway
      has left many unanswered questions about the hydrolysis mechanism. Therefore,
      detailed ONIOM(M06-2X/6-31G(d):AMBER) reaction potential energy surface scans are
      used to gain the first atomistic perspective of the repair pathway used by AAG.
      The lowest barrier for neutral 1,N(6)-ethenoadenine (epsilonA) and cationic N(3)
      methyladenine (3MeA) excision corresponds to a concerted (A(N)D(N)) mechanism,
      where our calculated DeltaG(?) = 87.3 kJ mol(-1) for epsilonA cleavage is
      consistent with recent kinetic data. The use of a concerted mechanism supports
      previous speculations that AAG uses a nonspecific strategy to excise both neutral
      (epsilonA) and cationic (3MeA) lesions. We find that AAG uses nonspecific active
      site DNA-protein pi-pi interactions to catalyze the removal of inherently more
      difficult to excise neutral lesions, and strongly bind to cationic lesions, which
      comes at the expense of raising the excision barrier for cationic substrates.
      Although proton transfer from the recently proposed general acid (protein-bound
      water) to neutral substrates does not occur, hydrogen-bond donation lowers the
      catalytic barrier, which clarifies the role of a general acid in the excision of
      neutral lesions. Finally, our work shows that the natural base adenine (A) is
      further inserted into the AAG active site than the damaged substrates, which
      results in the loss of a hydrogen bond with Y127 and misaligns the general base
      (E125) and water nucleophile to lead to poor nucleophile activation. Therefore,
      our work proposes how AAG discriminates against the natural purines in the
      chemical step and may also explain why some damaged pyrimidines are bound but are
      not excised by this enzyme.

PMID- 21877722
TI  - Neutral radical and singlet biradical forms of meso-free, -keto, and -diketo
      hexaphyrins(1.1.1.1.1.1): effects on aromaticity and photophysical properties.
AB  - We have investigated the electronic structures and photophysical properties of
      5,10,20,25-tetrakis(pentafluorophenyl)-substituted hexaphyrin(1.1.1.1.1.1) (1)
      and its meso-keto (2) and meso-diketo derivatives (3) using various spectroscopic
      measurements. In conjunction with theoretical calculations, these analyses
      revealed fundamental structure-property relationships within this series,
      including unusual ground-state electronic structures with neutral, monoradical,
      and singlet biradical character. The meso-free species 1 is a representative 26
      pi-electron aromatic compound and shows characteristic spectroscopic features,
      including a sharp Soret band, well-defined Q-like bands, and a moderately long
      excited state lifetime (tau = 138 ps). In contrast, the meso-keto derivative 2
      displays features characteristic of a neutral monoradical species at the ground
      state, including the presence of lower energy absorption bands in the NIR
      spectral region and a relatively short excited-state lifetime (13.9 ps). The meso
      diketo 3 exhibits features similar to those of 2, specifically NIR absorptions
      and a short excited-state lifetime (9.7 ps). Compound 3 is thus assigned as being
      a ground-state singlet biradicaloid. Two photon absorption (TPA) measurements
      revealed comparatively large sigma(2) values of 600 GM for 2 and 1600 GM for 3
      with excitation at lambda(ex) =1600 nm as compared to that observed for 1
      (sigma(2): 360 GM). The enhanced nonlinear optical properties of 2 and 3 are
      rationalized in terms of the open-shell electronic configuration allowing a
      large, field-induced fluctuation in the electron density (i.e., a large
      polarization). This interpretation is supported by theoretical evaluations of the
      static second hyperpolarizabilities (gamma) and gamma density analyses.
      Furthermore, nucleus-independent chemical shift (NICS) and harmonic oscillator
      model of aromaticity (HOMA) values and anisotropy of the induced current density
      (AICD) plots revealed a clear distinction in terms of the aromatic character of 1
      3. Importantly, the open-shell radicaloid 2 and singlet biradicaloid 3 can be
      formally regarded as 27 pi-electron nonaromatic and 26 pi-electron aromatic
      species, respectively, constrained within a dominant 28 pi-electron conjugated
      network. On the basis of the combined experimental and theoretical evidence, it
      is concluded that the meso-carbonyl groups of 2 and 3 play an important role in
      perturbing the macrocyclic pi-conjugation of the parent hexaphyrin structure 1.
      In particular, they lead to the imposition of intrinsic radical and biradical
      character on the molecule as a whole and thus easy-to-discern modifications of
      the overall electronic effects.

PMID- 21877723
TI  - Simultaneous stereoinversion and isomerization at the Asp-4 residue in betaB2
      crystallin from the aged human eye lenses.
AB  - The lens proteins are composed of alpha-, beta-, and gamma-crystallins that
      interact with each other to maintain the transparency and refractive power of the
      lens. Because the lens crystallins are long-lived proteins, they undergo various
      post-translational modifications including racemization, isomerization,
      deamidation, oxidation, glycation, and truncation. In betaB2-crystallin, which is
      the most abundant beta-crystallin, the deamidation of asparagine and glutamine
      residues has been reported. Here, we found that the aspartyl (Asp) residue at
      position 4 of betaB2-crystallin in the lenses of elderly human individuals
      undergoes a significant degree of inversion and isomerization to the biologically
      uncommon residue D-beta-Asp. Surprisingly, the D/L ratio of beta-Asp at position
      4 in betaB2-crystallin from elderly donors (67-77 year old) was 0.88-3.21. A D/L
      ratio of amino acids greater than 1.0 is defined as an inversion of configuration
      from the L- to D-form, rather than a racemization. These extremely high D/L
      ratios are equivalent to those of Asp-58 and Asp-151 (D/L ratio: 3.1 for Asp-58
      and 5.7 for Asp-151) in alphaA-crystallin from elderly donors (~80 year old) as
      reported previously. Initially, we identified specific Asp residues in the beta
      crystallin family of proteins that undergo a high degree of inversion. These
      results show that the isomerization and inversion of Asp residues occurs both in
      the alpha- and beta-crystallins of the lens. Inversion of these Asp residues
      directly affects the higher order structure of the protein. Hence, this
      modification may change crystallin-crystallin interactions and disrupt the
      function of crystallins in the lens.

PMID- 21877725
TI  - Proton transfer and dissociation of GlyLysH+ following O-H and N-H stretching
      mode excitations: dynamics simulations.
AB  - Proton transfer and dissociation processes following excitation of the OH or NH
      stretching modes of the proton-bound complex GlyLysH(+) are studied by classical
      trajectories. "On the fly" simulations with the PM3 semiempirical electronic
      structure method for the potential surface are used. Initial conditions are
      sampled to correspond to the v=1 excited state of the OH or NH stretching modes.
      Five different conformers of the complex are studied as initial structures. The
      main findings are (1) Photoinduced proton transfer is on the picosecond time
      scale. (2) Proton transfer is much faster than the processes of dissociation. (3)
      Proton transfer involves different sites. Most trajectories show sequences of two
      proton transfer events. (4) The proton transfer events show high selectivity with
      regard to the initially excited vibration and the initial structure. (5)
      Photodissociation of the complex occurs on a typical time scale of 100 ps. (6)
      Conformational transitions are found to be often faster than proton transfer.
      These results have implications for the mass spectrometry of complexes, for
      dynamics of proton wires, and for proton migration in proteins.

PMID- 21877726
TI  - Roles of Li+ and Zr4+ cations in the catalytic performances of Co(1
      x)M(x)Cr(2)O(4) (M = Li, Zr; x = 0-0.2) for methane combustion.
AB  - Co(1-x)M(x)Cr(2)O(4) (M = Li, Zr; x = 0-0.2) catalysts were prepared via the
      citric acid method and investigated for catalytic combustion of methane.
      Substitution at tetrahedral (A) sites with monovalent (Li) or tetravalent (Zr)
      metal ions led to a decrease or increase of the catalytic activity, respectively.
      The Co(0.95)Zr(0.05)Cr(2)O(4) catalyst proved to be the most active and its
      catalytic activity reached 90% of methane conversion at 448  degrees C, which
      dropped by 66  degrees C compared with that of the undoped CoCr(2)O(4) catalyst.
      XRD and Raman results indicated that lithium or zirconium substitution could
      modify the spinel structure and electronic properties. For lithium-doped
      catalysts, oxygen deficiency and a strong surface enrichment in lithium and
      chromium were detected. Zirconium substitution enhanced the reducibility of
      zirconium-doped catalysts and decreased the strength constant of both the Co-O
      band and the Cr-O band, which may contribute to the catalytic activity toward
      methane combustion. In addition, the prevalent catalytic combustion activity of
      the zirconium-substituted catalysts could be explained by their higher
      concentration of suprafacial, weakly chemisorbed oxygen.

PMID- 21877724
TI  - Fibrillation of the major curli subunit CsgA under a wide range of conditions
      implies a robust design of aggregation.
AB  - The amyloid fold is usually considered a result of protein misfolding. However, a
      number of studies have recently shown that the amyloid structure is also used in
      nature for functional purposes. CsgA is the major subunit of Escherichia coli
      curli, one of the most well-characterized functional amyloids. Here we show,
      using a highly efficient approach to prepare monomeric CsgA, that in vitro
      fibrillation of CsgA occurs under a wide variety of environmental conditions and
      that the resulting fibrils exhibit similar structural features. This highlights
      how fibrillation is "hardwired" into amyloid that has evolved for structural
      purposes in a fluctuating extracellular environment and represents a clear
      contrast to disease-related amyloid formation. Furthermore, we show that CsgA
      polymerization in vitro is preceded by the formation of thin needlelike
      protofibrils followed by aggregation of the amyloid fibrils.

PMID- 21877727
TI  - Biosupported bimetallic Pd-Au nanocatalysts for dechlorination of environmental
      contaminants.
AB  - Biologically produced monometallic palladium nanoparticles (bio-Pd) have been
      shown to catalyze the dehalogenation of environmental contaminants, but fail to
      efficiently catalyze the degradation of other important recalcitrant halogenated
      compounds. This study represents the first report of biologically produced
      bimetallic Pd/Au nanoparticle catalysts. The obtained catalysts were tested for
      the dechlorination of diclofenac and trichlorethylene. When aqueous bivalent
      Pd(II) and trivalent Au(III) ions were both added to concentrations of 50 mg L(
      1) and reduced simultaneously by Shewanella oneidensis in the presence of H(2),
      the resulting cell-associated bimetallic nanoparticles (bio-Pd/Au) were able to
      dehalogenate 78% of the initially added diclofenac after 24 h; in comparison, no
      dehalogenation was observed using monometallic bio-Pd or bio-Au. Other catalyst
      synthesis strategies did not show improved dehalogenation of TCE and diclofenac
      compared with bio-Pd. Synchrotron-based X-ray diffraction, (scanning)
      transmission electron microscopy and energy dispersive X-ray spectroscopy
      indicated that the simultaneous reduction of Pd and Au supported on cells of S.
      oneidensis resulted in the formation of a unique bimetallic crystalline
      structure. This study demonstrates that the catalytic activity and functionality
      of possibly environmentally more benign biosupported Pd-catalysts can be improved
      by coprecipitation with Au.

PMID- 21877728
TI  - Hormone discharges from a midwest tile-drained agroecosystem receiving animal
      wastes.
AB  - Manure is increasingly being viewed as a threat to aquatic ecosystems due to the
      introduction of natural and synthetic hormones from land application to
      agricultural fields. In the Midwestern United States, where most agricultural
      fields are tile-drained, there is little known about hormone release from fields
      receiving animal wastes. To this end, seven sampling stations (four in subsurface
      tile drains and three in the receiving ditch network) were installed at a Midwest
      farm where various types of animal wastes (beef, dairy, and poultry lagoon
      effluent, dairy solids, and subsurface injection of swine manure) are applied to
      agricultural fields. Water flow was continuously monitored and samples were
      collected for hormone analysis during storm events and baseline flow for a 15
      month study period. The compounds analyzed included the natural hormones 17alpha-
      and 17beta-estradiol, estrone, estriol, testosterone, and androstenedione and the
      synthetic androgens 17alpha- and 17beta-trenbolone and trendione. Hormones were
      detected in at least 64% of the samples collected at each station, with estrone
      being detected the most frequently and estriol the least. Testosterone and
      androstendione were detected more frequently than synthetic androgens, which were
      detected in fewer than 15% of samples. Hormone concentrations in subsurface tile
      drains increased during effluent irrigation and storm events. Hormones also
      appeared to persist over the winter, with increased concentrations coinciding
      with early thaws and snowmelt from fields amended with manure solids. The highest
      concentration of synthetic androgens (168 ng/L) observed coincided with a
      snowmelt. The highest concentrations of hormones in the ditch waters (87 ng/L for
      total estrogens and 52 ng/L for natural androgens) were observed in June, which
      coincides with the early life stage development period of many aquatic species in
      the Midwest.

PMID- 21877729
TI  - Electronically regulated thermally and light-gated electron transfer from anions
      to naphthalenediimides.
AB  - Anion-induced  electron transfer (ET) to pi-electron-deficient
      naphthalenediimides (NDIs) can be channeled through two distinct pathways by
      adjusting the Lewis basicity of the anion and the pi-acidity of the NDI: (1) When
      the anion and NDI are a strong electron donor and acceptor, respectively,
      positioning the HOMO of the anion above the LUMO of the NDI, a thermal anion ->
      NDI ET pathway is turned ON. (2) When the HOMO of a weakly Lewis basic anion
      falls below the LUMO of an NDI but still lies above its HOMO, the thermal ET is
      turned OFF, but light can activate an unprecedented anion -> (1)*NDI photoinduced
      ET pathway from the anion's HOMO to the photogenerated (1)*NDI's SOMO-1. Both
      pathways generate NDI(*-) radical anions.

PMID- 21877730
TI  - Palladium-catalyzed Heck reaction of aryl chlorides under mild conditions
      promoted by organic ionic bases.
AB  - An efficient Pd-catalyzed Heck reaction of aryl chlorides with olefins under mild
      conditions is described. High yields of products were achieved with n
      Bu(4)N(+)OAc(-) as base. Significantly, the temperature of the Heck reaction of
      diverse nonactivated aryl chlorides can be lowered to 80  degrees C. The new
      reaction system can also tolerate a wider range of olefins.

PMID- 21877731
TI  - Substrate-directable Heck reactions with arenediazonium salts. The regio- and
      stereoselective arylation of allylamine derivatives and applications in the
      synthesis of naftifine and abamines.
AB  - The palladium-catalyzed, substrate-directable Heck-Matsuda reaction of allylamine
      derivatives with arenediazonium salts is reported. The reaction proceeds under
      mild conditions, with excellent regio- and stereochemical control as a function
      of coordinating groups present in the allylamine substrate. The distance between
      the olefin moiety and the carbonylic system seems to play a key role regarding
      the regiocontrol. The method presents itself as robust, as simple to carry out,
      and with wide synthetic scope concerning the allylic substrates and the type of
      arenediazonium employed. The synthetic potential of the method is illustrated by
      the short total syntheses of the bioactive compounds naftifine, abamine, and
      abamine SG.

PMID- 21877732
TI  - Effect of cation size and charge on the interaction between silica surfaces in
      1:1, 2:1, and 3:1 aqueous electrolytes.
AB  - Application of two complementary AFM measurements, force vs separation and
      adhesion force, reveals the combined effects of cation size and charge (valency)
      on the interaction between silica surfaces in three 1:1, three 2:1, and three 3:1
      metal chloride aqueous solutions of different concentrations. The interaction
      between the silica surfaces in 1:1 and 2:1 salt solutions is fully accounted for
      by ion-independent van der Waals (vdW) attraction and electric double-layer
      repulsion modified by cation specific adsorption to the silica surfaces. The
      deduced ranking of mono- and divalent cation adsorption capacity (adsorbability)
      to silica, Mg(2+) < Ca(2+) < Na(+) < Sr(2+) < K(+) < Cs(+), follows cation bare
      size as well as cation solvation energy but does not correlate with hydrated
      ionic radius or with volume or surface ionic charge density. In the presence of
      3:1 salts, the coarse phenomenology of the force between the silica surfaces as a
      function of salt concentration resembles that in 1:1 and 2:1 electrolytes.
      Nevertheless, two fundamental differences should be noticed. First, the
      attraction between the silica surfaces is too large to be attributed solely to
      vdW force, hence implying an additional attraction mechanism or gross
      modification of the conventional vdW attraction. Second, neutralization of the
      silica surfaces occurs at trivalent cation concentrations that are 3 orders of
      magnitude smaller than those characterizing surface neutralization by mono- and
      divalent cations. Consequently, when trivalent cations are added to our cation
      adsorbability series the correlation with bare ion size breaks down abruptly. The
      strong adsorbability of trivalent cations to silica contrasts straightforward
      expectations based on ranking of the cationic solvation energies, thus suggesting
      a different adsorption mechanism which is inoperative or weak for mono- and
      divalent cations.

PMID- 21877733
TI  - Molecular dynamics simulation of free and forced BSA adsorption on a hydrophobic
      graphite surface.
AB  - The adsorption of bovine serum albumin (BSA) onto a hydrophobic graphite surface
      is studied using molecular-dynamics simulation. In addition to the free, that is,
      unsteered, adsorption, we also investigate forced adsorption, in which the action
      of an AFM tip pushing the protein with constant force to the surface is modeled.
      Using an implicit inviscid water model, the adsorption dynamics and energetics
      are monitored for two different initial protein orientations toward the surface.
      In all cases, we find that the protein partially unfolds and spreads on the
      surface. The spreading is in agreement with the well-known high biocompatibility
      of graphite-based implants. The denaturation is, however, greatly enhanced in the
      case of forced adsorption. We follow the position of the so-called lipid-binding
      pocket found in subdomain IIIA (Sudlow site II) during adsorption and find that
      it is tilted and moved toward the graphite surface in all cases, in agreement
      with its hydrophobic character. The relevance of our findings for the common
      measurement procedure of studying protein adhesion using AFM experiments is
      discussed.

PMID- 21877735
TI  - Strong and reversible binding of carbon dioxide in a green metal-organic
      framework.
AB  - The efficient capture and storage of gaseous CO(2) is a pressing environmental
      problem. Although porous metal-organic frameworks (MOFs) have been shown to be
      very effective at adsorbing CO(2) selectively by dint of dipole-quadruple
      interactions and/or ligation to open metal sites, the gas is not usually trapped
      covalently. Furthermore, the vast majority of these MOFs are fabricated from
      nonrenewable materials, often in the presence of harmful solvents, most of which
      are derived from petrochemical sources. Herein we report the highly selective
      adsorption of CO(2) by CD-MOF-2, a recently described green MOF consisting of the
      renewable cyclic oligosaccharide gamma-cyclodextrin and RbOH, by what is believed
      to be reversible carbon fixation involving carbonate formation and decomposition
      at room temperature. The process was monitored by solid-state (13)C NMR
      spectroscopy as well as colorimetrically after a pH indicator was incorporated
      into CD-MOF-2 to signal the formation of carbonic acid functions within the
      nanoporous extended framework.

PMID- 21877734
TI  - Do intermolecular interactions control crystallization abilities of glass-forming
      liquids?
AB  - Broadband dielectric spectroscopy was used to investigate molecular dynamics of
      three very similar systems: D-glucose, alpha-pentaacetylglucose, and beta
      pentaacetylglucose in a wide range of temperatures. We found out that two latter
      systems (differing only in location of the acetyl group attached to the first
      carbon in the sugar ring) reveal completely opposite tendencies to
      crystallization. Therefore, the aim of this Article was to investigate in detail
      molecular dynamics of both pentaacetylglucoses to assess what are the underlying
      of different crystallization abilities of so closely related carbohydrates. To
      analyze the kinetics of crystallization, we used Avrami and Avramov approaches.
      Interestingly, we found out that both alpha-and beta-pentaacetylglucose exhibit
      completely different crystallization mechanisms. In the first case, the value of
      Avrami exponent was estimated to be n = 2, whereas for the second carbohydrate
      this exponent was equaled to n = 5.5. Additionally, we have carried out
      isothermal time-dependent dielectric measurements on D-glucose to demonstrate
      that this saccharide is more stable than its acetyl derivatives. Results
      presented in this Article indicate that besides molecular mobility, the character
      of the intermolecular interactions might also be another important factor
      governing crystallization process. Surprisingly, this issue is not often
      addressed during studies on crystallization abilities of different glass-formers.
      Finally, additional optical measurements were carried out to get more detailed
      information about nucleation density, activation barrier for a crystal growth,
      and morphology of crystallization structures.

PMID- 21877736
TI  - Protein allostery at the solid-liquid interface: endoglucanase attachment to
      cellulose affects glucan clenching in the binding cleft.
AB  - At phase boundaries, physical activities of enzymes such as substrate
      complexation play critical roles in driving biocatalysis. A prominent example is
      the cellulase cocktails secreted by fungi and bacteria for deconstructing
      crystalline cellulose in biomass into soluble sugars. At interfaces, molecular
      mechanisms of the physical steps in biocatalysis remain elusive due to the
      difficulties of characterizing protein action with high temporal and spatial
      resolution. Here, we focus on endoglucanase I (Cel7B) from the fungus 
      Trichoderma reesei  that hydrolyzes glycosidic bonds on cellulose randomly. We
      employ all-atom molecular dynamics (MD) simulations to elucidate the interactions
      of the catalytic domain (CD) of Cel7B with a cellulose microfibril before and
      after complexing a glucan chain in the binding cleft. The calculated mechanical
      coupling networks in Cel7B-glucan and Cel7B-microfibril complexes reveal a
      previously unresolved allosteric coupling at the solid-liquid interface:
      attachment of the Cel7B CD to the cellulose surface affects glucan chain
      clenching in the binding cleft. Alternative loop segments of the Cel7B CD were
      found to affix to intact or defective surface structures on the microfibril,
      depending on the complexation state. From a multiple sequence alignment, residues
      in surface-affixing segments show strong conservation, highlighting the
      functional importance of the physical activities that they facilitate. Surface
      affixing residues also demonstrate significant sequence correlation with active
      site residues, revealing the functional connection between complexation and
      hydrolysis. Analysis of the Cel7B CD exemplifies that the mechanical coupling
      networks calculated from atomistic MD simulations can be used to capture the
      conservation and correlation in sequence alignment.

PMID- 21877737
TI  - Tandem reactions of 1,2-allenic ketones leading to substituted benzenes and
      alpha,beta-unsaturated nitriles.
AB  - One-pot double Michael addition/intramolecular aldol reaction/decarboxylation of
      1,2-allenic ketones with cyanoacetate offers an efficient and convenient approach
      to highly functionalized benzenes. With 2-substituted cyanoacetates, the reaction
      proceeds via a different tandem process to afford alpha,beta-unsaturated nitriles
      effectively.

PMID- 21877738
TI  - Data-driven high-throughput prediction of the 3-D structure of small molecules:
      review and progress. A response from the Cambridge Crystallographic Data Centre.

PMID- 21877739
TI  - Lignin-derived phenols in Houston aerosols: implications for natural background
      sources.
AB  - Solvent-extractable monomeric methoxyphenols in aerosol samples conventionally
      have been used to indicate the influence of biomass combustion. In addition, the
      presence of lignin oxidation products (LOP), derived from the CuO oxidation of
      vascular plant organic matter, can help trace the source and inputs of primary
      biological particles in aerosols. Ambient aerosols (coarse and fine) collected in
      Houston during summer 2010 were analyzed by gas chromatography-mass spectrometry
      to characterize monomeric and polymeric sources of LOPs. This is the first time
      polymeric forms of the LOPs have been characterized in ambient aerosols. The
      absence or small concentrations of solvent-extractable monomeric LOPs and
      levoglucosan isomers point to the limited influence of biomass burning during the
      sampling period. The trace levels of anhydrosugar concentrations most likely
      result from long-range transport. This observation is supported by the absence of
      co-occurring lignin monomers that undergo photochemical degradation during
      transport. The larger concentration (142 ng m(-3)) of lignin polymers in coarse
      aerosols shows the relative importance of primary biological aerosol particles,
      even in the urban atmosphere. The LOP parameters suggest a predominant influence
      from woody tissue of angiosperms, with minor influence from soft tissues,
      gymnosperms, and soil organic matter.

PMID- 21877740
TI  - Charybdotoxin unbinding from the mKv1.3 potassium channel: a combined
      computational and experimental study.
AB  - Charybdotoxin, belonging to the group of so-called scorpion toxins, is a short
      peptide able to block many voltage-gated potassium channels, such as mKv1.3, with
      high affinity. We use a reliable homology model based on the high-resolution
      crystal structure of the 94% sequence identical homologue Kv1.2 for charybdotoxin
      docking followed by molecular dynamics simulations to investigate the mechanism
      and energetics of unbinding, tracing the behavior of the channel protein and
      charybdotoxin during umbrella-sampling simulations as charybdotoxin is moved away
      from the binding site. The potential of mean force is constructed from the
      umbrella sampling simulations and combined with K(d) and free energy values
      gained experimentally using the patch-clamp technique to study the free energy of
      binding at different ion concentrations and the mechanism of the charybdotoxin
      mKv1.3 binding process. A possible charybdotoxin binding mechanism is deduced
      that includes an initial hydrophobic contact followed by stepwise electrostatic
      interactions and finally optimization of hydrogen bonds and salt bridges.

PMID- 21877741
TI  - On the mechanism of Re(I)-carboxylate bond cleavage by perchloric acid: a kinetic
      and spectroscopic study.
AB  - We have studied the reaction between pz-CO(2)-Re(CO)(3)(bpy) and perchloric acid
      in acetonitrile by following the UV-vis and IR spectral changes in the reaction
      mixture. A fast equilibrium was found to be established between solvated protons,
      pz-CO(2)-Re(CO)(3)(bpy), and the protonated intermediate [pz-C(OH)O
      Re(CO)(3)(bpy)](+) which finally yields pz-COOH and Re(CO)(3)(bpy)(CH(3)CN)(+) as
      reaction products. This intermediate has been characterized by UV-vis and IR
      spectroscopies and by DFT calculations. The fully optimized DFT/CPCM structures
      for pz-CO(2)-Re(CO)(3)(bpy) and [pz-C(OH)O-Re(CO)(3)(bpy)](+) were compared with
      the X-ray structure of pz-CO(2)-Re(CO)(3)(bpy). The structural parameters
      associated with the carboxyl group in the protonated intermediate are between
      those of pz-CO(2)-Re(CO)(3)(bpy) and pz-COOH. Multivariate curve resolution
      methods were employed to obtain the spectrum of the protonated intermediate and
      the concentration profiles from the full matrix of time-resolved UV-vis spectra.
      The proposed mechanism was numerically simulated by using Runge-Kutta methods.
      Model parameters were estimated by nonlinear regression fitting of the
      concentration profiles, yielding values of log(K) = 4.9 +/- 0.3 and k = 0.16 +/-
      0.03 min(-1) for the formation equilibrium constant and the decay rate constant
      of the protonated intermediate, respectively.

PMID- 21877742
TI  - Graphene supported platinum nanoparticle counter-electrode for enhanced
      performance of dye-sensitized solar cells.
AB  - Composites of few layered graphene (G) and platinum (Pt) nanoparticles (NP) with
      different loadings of Pt were used as counter electrode (CE) in dye-sensitized
      solar cell (DSSC). NPs were deposited directly on to G using pulsed laser
      ablation method (PLD). DSSCs formed using the composite CEs show improved
      performance compared to conventional Pt thin film electrode (Std Pt) and
      unsupported Pt NPs. Composite with 27% loading of Pt shows 45% higher efficiency
      (eta = 2.9%), greater short circuit current (J(sc) = 6.67 mA cm(-2)), and open
      circuit voltage (V(oc) = 0.74 V) without any loss of the fill factor (FF = 58%)
      as compared to the cells fabricated using Std Pt electrodes. Values of eta, J(sc)
      and V(oc) for DSSC using Std Pt CE were 2%, 5.05 mA cm(-2) and 0.68 V,
      respectively. Electrochemical impedance spectroscopy using I(-)(3)/I(-) redox
      couple confirm lower values of charge transfer resistance for the composite
      electrodes, e.g., 2.36 Omega cm(2) as opposed to 7.73 Omega cm(2) of Std Pt. The
      better catalytic activity of these composite materials is also reflected in the
      stronger I(-)(3) reduction peaks in cyclic voltammetry scans.

PMID- 21877743
TI  - Superhard tungsten tetraboride films prepared by pulsed laser deposition method.
AB  - Attempts to synthesize and/or theoretically predict new superhard materials are
      the subject of an intense research activity. The trials to deposit them in the
      form of films have just began. WB(2) (77 wt % WB(2) and 23 wt % WB(4)) and WB(4)
      (65 wt % WB(4) and 35 wt % WB(2)) polycrystalline bulk samples were obtained in
      this work via electron beam synthesis technique and, subsequently, used as
      targets for films preparation by the pulsed laser deposition method. The targets
      were irradiated by a frequency-doubled Nd:glass laser with a pulse duration of
      250 fs. The films grown on SiO(2) substrates at 600  degrees C were characterized
      by X-ray diffraction, scanning electron and atomic force microscopies, and
      Vickers microhardness technique. The deposited films are composed of WB(4). The
      intrinsic film hardness, calculated according to the "law-of-mixtures" model,
      lies in the superhardness region 42-50 GPa.

PMID- 21877744
TI  - Hydrothermal synthesis and electrochemical properties of Li3V2(PO4)3/C-based
      composites for lithium-ion batteries.
AB  - To improve performance at higher rates, we developed a hydrothermal method to
      prepare carbon-coated monoclinic lithium vanadium phosphate (Li(3)V(2)(PO(4))(3))
      powder to be used as a cathode material for Li-ion batteries. The structural,
      morphological and electrochemical properties were characterized by X-ray
      diffraction (XRD), scanning and transmission electron microscopy (SEM and TEM),
      and galvanostatic charge-discharge cycling. A superior cycle and rate behavior
      are demonstrated for Li(3)V(1.85)Sc(0.15)(PO(4))(3)/C and
      Li(2.96)Ca(0.02)V(2)(PO(4))(3)/C electrodes at charge-discharge current rates
      above 5C.

PMID- 21877745
TI  - Mechanical stress affects glucagon fibrillation kinetics and fibril structure.
AB  - Mechanical stress can strongly influence the capability of a protein to aggregate
      and the kinetics of aggregation, but there is little insight into the underlying
      mechanism. Here we study the effect of different mechanical stress conditions on
      the fibrillation of the peptide hormone glucagon, which forms different fibrils
      depending on temperature, pH, ionic strength, and concentration. A combination of
      spectroscopic and microscopic data shows that fibrillar polymorphism can also be
      induced by mechanical stress. We observed two classes of fibrils: a low-stress
      and a high-stress class, which differ in their kinetic profiles, secondary
      structure as well as morphology and that are able to self-propagate in a template
      dependent fashion. The bending rigidity of the low-stress fibrils is sensitive to
      the degree of mechanical perturbation. We propose a fibrillation model, where
      interfaces play a fundamental role in the switch between the two fibrillar
      classes. Our work also raises the cautionary note that mechanical perturbation is
      a potential source of variability in the study of fibrillation mechanisms and
      fibril structures.

PMID- 21877746
TI  - Mechanisms of tannin-induced trypsin inhibition: a molecular approach.
AB  - Association of procyanidins with enzymes has drawn attention over the past few
      years. This work aimed to bring insights on interaction of the protease trypsin
      with the procyanidin dimer (B3). This interaction was characterized by
      fluorescence quenching, saturation transfer difference (STD) NMR, molecular
      modeling, and through an enzymatic inhibition assay. Further studies were
      conducted regarding the influence of pectin on the binding process. A general
      overview of the binding process may be outlined as follows: a) at low procyanidin
      concentrations (below the critical micellar concentration-(CMC)) a specific
      interaction probably driven by hydrogen bonds between the protein backbone and
      the procyanidin occurs and is associated with the reduction of both enzyme
      activity and fluorescence; b) at high procyanidin concentration (above the CMC)
      the interaction becomes nonspecific. This variation in both nature and extent of
      the interaction with the variation of procyanidin concentration shows how tannin
      self-association may affect the interaction between tannins and proteins. It was
      also shown that the mechanism through which pectin affects the interaction
      between procyanidin B3 and trypsin is of a competitive type.

PMID- 21877747
TI  - New approximate analytical expressions for transient concentration profiles and
      current pertaining to a homogeneous chemical reaction at hemispherical
      microelectrodes.
AB  - A mathematical model corresponding to homogeneous chemical reactions under
      transient chronoamperometry conditions at hemispherical microelectrodes has been
      developed. The analytical solutions for the concentration of species and current
      were obtained using Duhamel's theorem. This closed-form theoretical expression
      pertains to the transient concentration profiles and fluxes of chemical species
      involved in chemical and electrochemical reactions at hemispherical
      microelectrodes. As t -> infinity, the analytical expressions corresponding to
      the concentration and current approach steady-state values. The solutions
      obtained are explicit only under limiting current conditions. The approximate
      expressions for concentrations and current as functions of time corresponding to
      the EC' and CE mechanisms at hemispherical microelectrodes are also reported.

PMID- 21877748
TI  - Hofmeister effect on the interfacial dynamics of single polymer molecules.
AB  - The Hofmeister effect on interfacial dynamics has been discovered for single
      charged polymer molecules (sodium polystyrene sulfonate) adsorbed on a
      hydrophobic surface from an aqueous solution. The presence of ions in the aqueous
      solution affects the surface diffusivity, and its amplitudes and the surface
      friction follow the Hofmeister series-the kosmotropic ions slowed down the
      surface diffusivity and the chaotropic ions speeded it up. The amplitude of the
      surface friction exhibits a good correlation with the surface tension increment,
      indicating the interfacial feature of the Hofmeister effect.

PMID- 21877749
TI  - Modular strategy for the construction of radiometalated antibodies for positron
      emission tomography based on inverse electron demand Diels-Alder click chemistry.
AB  - A modular system for the construction of radiometalated antibodies was developed
      based on the bioorthogonal cycloaddition reaction between 3-(4-benzylamino)
      1,2,4,5-tetrazine and the strained dienophile norbornene. The well-characterized,
      HER2-specific antibody trastuzumab and the positron emitting radioisotopes (64)Cu
      and (89)Zr were employed as a model system. The antibody was first covalently
      coupled to norbornene, and this stock of norbornene-modified antibody was then
      reacted with tetrazines bearing the chelators 1,4,7,10-tetraazacyclo-dodecane
      1,4,7,10-tetraacetic acid (DOTA) or desferrioxamine (DFO) and subsequently
      radiometalated with (64)Cu and (89)Zr, respectively. The modification strategy is
      simple and robust, and the resultant radiometalated constructs were obtained in
      high specific activity (2.7-5.3 mCi/mg). For a given initial stoichiometric ratio
      of norbornene to antibody, the (64)Cu-DOTA- and (89)Zr-DFO-based probes were
      shown to be nearly identical in terms of stability, the number of chelates per
      antibody, and immunoreactivity (>93% in all cases). In vivo PET imaging and acute
      biodistribution experiments revealed significant, specific uptake of the (64)Cu-
      and (89)Zr-trastuzumab bioconjugates in HER2-positive BT-474 xenografts, with
      little background uptake in HER2-negative MDA-MB-468 xenografts or other tissues.
      This modular system-one in which the divergent point is a single covalently
      modified antibody stock that can be reacted selectively with various chelators
      will allow for both greater versatility and more facile cross-comparisons in the
      development of antibody-based radiopharmaceuticals.

PMID- 21877750
TI  - Gallium-68 complex of a macrobicyclic cage amine chelator tethered to two
      integrin-targeting peptides for diagnostic tumor imaging.
AB  - Tumor-targeting peptides radiolabeled with positron-emitting (68)Ga are promising
      candidates as new noninvasive diagnostic agents for positron emission tomography
      (PET). The targeting peptides are tethered to a chelator that forms a stable
      coordination complex with Ga(3+) that is inert to dissociation of Ga(3+)in vivo.
      Metal complexes of macrobicyclic hexaamine "sarcophagine" (sar = 3,6,10,13,16,19
      hexaazabicyclo[6.6.6]icosane) ligands exhibit remarkable stability as a result of
      the encapsulating nature of the cage amine ligand. A Ga(3+) sarcophagine complex,
      [Ga-(1-NH(3)-8-NH(2)-sar)](4+), has been characterized using X-ray
      crystallography, demonstrating that Ga(3+) is coordinated to six nitrogen atoms
      in a distorted octahedral complex. A bifunctional derivative of (NH(2))(2)sar,
      possessing two aliphatic linkers with carboxylic acid functional groups has been
      attached to two cyclic-RGD peptides that target the alpha(v)beta(3) integrin
      receptor that is overexpressed in some types of tumor tissue. This dimeric
      species can be radiolabeled with (68)Ga(3+) in >98% radiochemical yield and
      (68)Ga(3+) does not dissociate from the ligand in the presence of transferrin, an
      endogenous protein with high affinity for Ga(3+). Biodistribution and micro-PET
      imaging studies in tumor-bearing mice indicate that the tracer accumulates
      specifically in tumors with high integrin expression. The high tumor uptake is
      coupled with low nonspecific uptake and clearance predominantly through the
      kidneys resulting in high-quality PET images in animal models.

PMID- 21877751
TI  - DOTA-amide lanthanide tag for reliable generation of pseudocontact shifts in
      protein NMR spectra.
AB  - Structural studies of proteins and protein-ligand complexes by nuclear magnetic
      resonance (NMR) spectroscopy can be greatly enhanced by site-specific attachment
      of lanthanide ions to create paramagnetic centers. In particular, pseudocontact
      shifts (PCS) generated by paramagnetic lanthanides contain important and unique
      long-range structure information. Here, we present a high-affinity lanthanide
      binding tag that can be attached to single cysteine residues of proteins. The new
      tag has many advantageous features that are not available in this combination
      from previously published tags: (i) it binds lanthanide ions very tightly,
      minimizing the generation of nonspecific effects, (ii) it produces PCSs with high
      reliability as its bulkiness prevents complete motional averaging of PCSs, (iii)
      it can be attached to single cysteine residues, alleviating the need of detailed
      prior knowledge of the 3D structure of the target protein, and (iv) it does not
      display conformational exchange phenomena that would increase the number of
      signals in the NMR spectrum. The performance of the tag is demonstrated with the
      N-terminal domain of the E. coli arginine repressor and the A28C mutant of human
      ubiquitin.

PMID- 21877752
TI  - Secreted ERBB3 isoforms are serum markers for early hepatoma in patients with
      chronic hepatitis and cirrhosis.
AB  - Most hepatocellular carcinoma (HCC) is generated from chronic hepatitis and
      cirrhosis. To discover new markers for early HCC in patients with chronic
      hepatitis and cirrhosis, we initiated our search in the interstitial fluid of
      tumor (TIF) via differential gel electrophoresis and antibody arrays and
      identified secreted ERBB3 isoforms (sERBB3). The performance of serum sERBB3 in
      diagnosis of HCC was analyzed using receiver operating characteristic curves
      (ROC). The serum sERBB3 level was significantly higher in HCC than in cirrhosis
      (p < 0.001) and chronic hepatitis (p < 0.001). The accuracy of serum sERBB3 in
      detection of HCC was further validated in two independent sets of patients. In
      discrimination of early HCC from chronic hepatitis or cirrhosis, serum sERBB3 had
      a better performance than alpha-fetoprotein (AFP) (areas under ROC [AUC]: sERBB3
      vs AFP = 93.1 vs 81.0% from chronic hepatitis and 70.9 vs 62.7% from cirrhosis).
      Combination of sERBB3 and AFP further improved the accuracy in detection of early
      HCC from chronic hepatitis (AUC = 97.1%) or cirrhosis (AUC = 77.5%). Higher serum
      sERBB3 levels were associated with portal-vein invasion and extrahepatic
      metastasis of HCC (p = 0.017). Therefore, sERBB3 are serum markers for early HCC
      in patients with chronic hepatitis and cirrhosis.

PMID- 21877753
TI  - Scaffold diversity of exemplified medicinal chemistry space.
AB  - The scaffold diversity of 7 representative commercial and proprietary compound
      libraries is explored for the first time using both Murcko frameworks and
      Scaffold Trees. We show that Level 1 of the Scaffold Tree is useful for the
      characterization of scaffold diversity in compound libraries and offers
      advantages over the use of Murcko frameworks. This analysis also demonstrates
      that the majority of compounds in the libraries we analyzed contain only a small
      number of well represented scaffolds and that a high percentage of singleton
      scaffolds represent the remaining compounds. We use Tree Maps to clearly
      visualize the scaffold space of representative compound libraries, for example,
      to display highly populated scaffolds and clusters of structurally similar
      scaffolds. This study further highlights the need for diversification of compound
      libraries used in hit discovery by focusing library enrichment on the synthesis
      of compounds with novel or underrepresented scaffolds.

PMID- 21877754
TI  - Chemical modifications of peptides and their impact on food properties.

PMID- 21877755
TI  - Occurrence of iodinated X-ray contrast media and their biotransformation products
      in the urban water cycle.
AB  - A LC tandem MS method was developed for the simultaneous determination of four
      iodinated X-ray contrast media (ICM) and 46 ICM biotransformation products (TPs)
      in raw and treated wastewater, surface water, groundwater, and drinking water.
      Recoveries ranged from 70% to 130%, and limits of quantification (LOQ) varied
      between 1 ng/L and 3 ng/L for surface water, groundwater and drinking water, and
      between 10 ng/L and 30 ng/L for wastewater. In a conventional wastewater
      treatment plant, iohexol, iomeprol, and iopromide were transformed to >80%, while
      iopamidol was transformed to 35%. In total, 26 TPs were detected above their LOQ
      in WWTP effluents. A significant change in the pattern of ICM TPs was observed
      after bank filtration and groundwater infiltration under aerobic conditions.
      Predominately, these TPs are formed at the end of the microbial transformation
      pathways in batch experiments with soil and sediment. These polar ICM TPs, such
      as iohexol TP599, iomeprol TP643, iopromide TP701A, and iopromide TP643, were not
      or only partially removed during drinking water treatment. As a consequence,
      several ICM TPs were detected in drinking water, at concentration levels
      exceeding 100 ng/L, with a maximum of 500 ng/L for iomeprol TP687.

PMID- 21877756
TI  - Formal Diels-Alder reactions of chalcones and formylcyclopropanes catalyzed by
      chiral N-heterocyclic carbenes.
AB  - Highly enantioselective (formal) hetero-Diels-Alder reactions between chalcones
      and formylcyclopropanes are disclosed. The challenging N-heterocyclic carbene
      (NHC)-bounded enolate intermediates from formylcyclopropanes were captured for
      new C-C bond forming reactions. The reaction products were obtained with high
      diastereo- and enantioselectivities and could be easily transformed to optically
      pure multisubstituted cyclohexane derivatives.

PMID- 21877757
TI  - Natural 37Ar concentrations in soil air: implications for monitoring underground
      nuclear explosions.
AB  - For on-site inspections (OSI) under the Comprehensive Nuclear-Test-Ban Treaty
      (CTBT) measurement of the noble gas 37Ar is considered an important technique.
      37Ar is produced underground by neutron activation of Calcium by the reaction
      40Ca(n,alpha)37Ar. The naturally occurring equilibrium 37Ar concentration balance
      in soil air is a function of an exponentially decreasing production rate from
      cosmic ray neutrons with increasing soil depth, diffusive transport in the soil
      air, and radioactive decay (T(1/2): 35 days). In this paper for the first time,
      measurements of natural 37Ar activities in soil air are presented. The highest
      activities of ~100 mBq m-3 air are 2 orders of magnitude larger than in the
      atmosphere and are found in 1.5-2.5 m depth. At depths > 8 m 37Ar activities are
      < 20 mBq m-3 air. After identifying the main 37Ar production and gas transport
      factors the expected global activity range distribution of 37Ar in shallow
      subsoil (0.7 m below the surface) was estimated. In high altitude soils, with
      large amounts of Calcium and with low gas permeability, 37Ar activities may reach
      values up to 1 Bq m-3.

PMID- 21877758
TI  - Formation of nanocolloidal metacinnabar in mercury-DOM-sulfide systems.
AB  - Direct determination of mercury (Hg) speciation in sulfide-containing
      environments is confounded by low mercury concentrations and poor analytical
      sensitivity. Here we report the results of experiments designed to assess mercury
      speciation at environmentally relevant ratios of mercury to dissolved organic
      matter (DOM) (i.e., <4 nmol Hg (mg DOM)(-1)) by combining solid phase extraction
      using C(18) resin with extended X-ray absorption fine structure (EXAFS)
      spectroscopy. Aqueous Hg(II) and a DOM isolate were equilibrated in the presence
      and absence of 100 MUM total sulfide. In the absence of sulfide, mercury
      adsorption to the resin increased as the Hg:DOM ratio decreased and as the
      strength of Hg-DOM binding increased. EXAFS analysis indicated that in the
      absence of sulfide, mercury bonds with an average of 2.4 +/- 0.2 sulfur atoms
      with a bond length typical of mercury-organic thiol ligands (2.35 A). In the
      presence of sulfide, mercury showed greater affinity for the C(18) resin, and its
      chromatographic behavior was independent of Hg:DOM ratio. EXAFS analysis showed
      mercury-sulfur bonds with a longer interatomic distance (2.51-2.53 A) similar to
      the mercury-sulfur bond distance in metacinnabar (2.53 A) regardless of the
      Hg:DOM ratio. For all samples containing sulfide, the sulfur coordination number
      was below the ideal four-coordinate structure of metacinnabar. At a low Hg:DOM
      ratio where strong binding DOM sites may control mercury speciation (1.9 nmol mg(
      1)) mercury was coordinated by 2.3 +/- 0.2 sulfur atoms, and the coordination
      number rose with increasing Hg:DOM ratio. The less-than-ideal coordination
      numbers indicate metacinnabar-like species on the nanometer scale, and the
      positive correlation between Hg:DOM ratio and sulfur coordination number suggests
      progressively increasing particle size or crystalline order with increasing
      abundance of mercury with respect to DOM. In DOM-containing sulfidic systems
      nanocolloidal metacinnabar-like species may form, and these species need to be
      considered when addressing mercury biogeochemistry.

PMID- 21877759
TI  - Pro-bone and antifat effects of green tea and its polyphenol, epigallocatechin,
      in rat mesenchymal stem cells in vitro.
AB  - Green tea has been demonstrated recently as a potent bone supportive agent. Our
      previous studies showed that green tea and its polyphenolic constituents can
      promote bone-forming osteoblast activities and inhibit the bone-resorpting
      osteoclast formation. The objective of the present study was to investigate
      whether green tea and its components can regulate the osteogenic and adipogenic
      differentiation in pluripotent rat mesenchymal stem cells (MSCs). The rat MSCs
      were isolated from the bone marrow of tibiae and femora. The cells were treated
      with decaffeinated green tea extract (GTE) and six tea polyphenols under
      osteogenic induction. The alkaline phosphatase (ALP) activities and matrix
      calcium (Ca) deposition were assessed after 7 and 14 days of treatment. Our
      results demonstrated that GTE could significantly increase ALP dose dependently
      in the concentrations without cytotoxicity (0-100 MUg/mL). Among six tested tea
      polyphenols, epigallocatechin (EGC) was shown to be the most effective in
      promoting osteogenic differentiation. At 20 MUM, EGC increased ALP levels and Ca
      deposition significantly by 2.3- and 1.7-fold, respectively, when compared with
      the control group. EGC also increased the mRNA expression of bone formation
      markers runt-related transcription factor 2, ALP, osteonectin, and osteopontin.
      Furthermore, EGC demonstrated its antiadipogenicity by decreasing the adipocyte
      formation and inhibiting the mRNA expression levels of the adipogenic markers
      peroxisome proliferator-activated receptor gamma, ccaat/enhancer-binding protein
      beta, and fatty acid binding protein 4. In conclusion, this is the first report
      of the dual action of green tea polyphenol EGC in promoting osteogenesis and
      inhibiting adipocyte formation in MSCs. Our results provide scientific evidence
      to support the potential use of green tea in supporting the bone against
      degenerative diseases such as osteoporosis.

PMID- 21877760
TI  - Mycoplasma gallisepticum produces a histone-like protein that recognizes base
      mismatches in DNA.
AB  - Mycoplasmas are the smallest known microorganisms, with drastically reduced
      genome sizes. One of the essential biochemical pathways lost in mycoplasmas is
      methylation-mediated DNA repair (MMR), which is responsible for correction of
      base substitutions, insertions, and deletions in both bacteria and higher
      organisms. We found that the histone-like protein encoded by the himA/hup_2 gene
      of Mycoplasma gallisepticum (mgHU) recognizes typical MMR substrates, in contrast
      to homologues from other species. The recognition of substitution mismatches is
      sequence-dependent, with affinities decreasing in the following order: CC > CT =
      TT > AA = AC. Insertions or deletions of one nucleotide are also specifically
      recognized with the following sequence-dependent preference: A = T > C. One
      nucleotide lesions involving guanine are bound only weakly, and this binding is
      indistinguishable from binding to intact DNA. Although mgHU is dissimilar to
      Escherichia coli HU, expression in a slow-growing hupAB E. coli strain restores
      wild-type growth. The results indicate that mgHU executes all essential functions
      of bacterial architectural proteins. The origin and the possible role of enhanced
      specificity for typical MMR substrates are discussed.

PMID- 21877761
TI  - Effect of Ipragliflozin (ASP1941), a novel selective sodium-dependent glucose co
      transporter 2 inhibitor, on urinary glucose excretion in healthy subjects.
AB  - BACKGROUND: Hyperglycaemia is associated with serious complications, significant
      morbidity and death. Despite the availability of a wide range of therapeutic
      options, many patients with diabetes mellitus fail to achieve or maintain
      recommended glycaemic goals. Ipragliflozin (ASP1941) is a novel, selective
      inhibitor of the sodium-dependent glucose co-transporter 2, which is highly
      expressed in the proximal tubules of the kidneys. It suppresses renal glucose
      reabsorption and increases urinary glucose excretion (UGE), potentially providing
      an insulin-independent treatment option for type 2 diabetes. METHODS: This
      multiple ascending-dose study assessed the safety, tolerability, pharmacokinetics
      and pharmacodynamics of ipragliflozin in healthy subjects after single doses and
      multiple once-daily doses for 10 days (dose levels: 5-600 mg). RESULTS:
      Ipragliflozin was well tolerated following single and multiple once-daily oral
      dosing. Ipragliflozin was rapidly absorbed with a median time to reach the
      maximum plasma concentration of 1.3 hours after the last dose. The area under the
      plasma concentration-time curve increased proportionally with increasing dose.
      The mean elimination half-life was 12 hours following the last dose.
      Ipragliflozin dose dependently increased UGE up to a maximum of approximately 59
      g (327 mmol) of glucose excreted over 24 hours following multiple doses, without
      affecting plasma glucose levels in healthy subjects. CONCLUSION: Administration
      of ipragliflozin was well tolerated and resulted in a rapid, dose-dependent
      increase in glucosuria. Pharmacodynamic and pharmacokinetic data suggest that
      ipragliflozin is suitable for prolonged once-daily oral treatment.

PMID- 21877763
TI  - Botulinum toxin for glabellar lines: a review of the efficacy and safety of
      currently available products.
AB  - Facial rhytides represent a widespread aesthetic concern. In particular,
      glabellar lines are perceived as a sign of aging and may give an erroneous
      impression of negative emotions. The onset of glabellar lines is closely related
      to the movements of the underlying muscles. Botulinum toxins inhibit the release
      of acetylcholine into the synaptic cleft and therefore result in temporary muscle
      paralysis. The observation that botulinum toxin (BTX) smoothed facial lines when
      used therapeutically led researchers to study the toxin effect on glabellar
      lines. Nowadays, the use of BTX to smooth glabellar frown lines represents the
      leading procedure in aesthetic facial treatments and an increasing number of BTX
      formulations are becoming available. This article provides a comparative
      evaluation of currently available BTX options for the treatment of glabellar
      lines. Toxins have been divided into three groups, based on whether they have
      obtained approval for cosmetic use (approved treatments) or not (off-label
      treatments), or whether they are still under investigation (experimental
      treatments). We examine the basic similarities and differences between available
      botulinum toxins, and summarize the pharmacokinetics and dosing. All approved
      treatments consist of BTX type A (BTX-A) and differ in their molecular weight, as
      some formulations are made of a BTX-A complex of 900 kDa while the latest option
      on the market is a 150 kDa BTX-A that is free from complexing proteins. As for
      the dosage, the important aspect that emerges from this comparison is that even
      within a given serotype, such as BTX-A, formulations are not interchangeable as
      each possesses distinctive characteristics that are attributed to the unique
      toxin purification and manufacturing processes. There is a substantial body of
      published evidence on the use of these approved treatments for facial
      enhancement, proving efficacy and safety. We investigate the methods of
      evaluation used for each toxin and review the safety and efficacy data reported
      in the literature. Minor adverse effects, such as headache, blepharoptosis, and
      injection-site reactions, are relatively frequent but transient, whilst major
      adverse effects are rare. Some botulinum toxins, i.e. BTX type B, that are
      approved for therapeutic applications are used off-label for cosmetic
      indications, thus without the approval of the health regulatory committees and
      without sufficient published evidence on safety and efficacy. As for experimental
      treatments, a number of BTX products are currently in development or have been
      recently launched for aesthetic applications. These products have been
      specifically designed to overcome some of the limitations present in the older
      generation of products. However, some of these toxins may be easily purchased via
      the Internet, without having any license or approval for cosmetic or therapeutic
      indications; these products must be considered unsafe and are potentially a
      severe health risk for patients.

PMID- 21877762
TI  - The effects of a small dose of dexamethasone on cell adhesion molecules during
      laparoscopic cholecystectomy.
AB  - BACKGROUND AND OBJECTIVE: There are only a few publications on the effects of
      dexamethasone on the plasma levels of cell adhesion molecules (CAMs). The goal of
      this study was to investigate the effects of dexamethasone 4 mg on the
      perioperative plasma levels of CAMs (soluble intercellular adhesion molecules
      [sICAM-1] and soluble vascular cell adhesion molecules [sVCAM-1]) during
      laparoscopic cholecystectomy. METHODS: Forty-two patients undergoing laparoscopic
      cholecystectomy under total intravenous anesthesia were enrolled and randomly
      divided into two groups: the first group received dexamethasone 4 mg (DEX group,
      n = 21) and the second group were controls (C group, n = 21). Plasma levels of
      sICAM-1 and sVCAM-1 were assessed before anesthesia, after induction (before
      surgery), and at 2 and 24 hours after surgery, respectively. Comparisons were
      performed for area under the plasma concentration-time curve (AUC) and within
      group values. RESULTS: AUC comparison for sICAM-1 showed significantly increased
      levels in the C group (p = 0.036), while there was no significant difference for
      sVCAM-1 (p = 0.052). Within-group analysis showed increased levels for both sICAM
      1 and sVCAM-1 in the C group at 24 hours postoperatively (p = 0.35 and p = 0.025,
      respectively). CONCLUSIONS: In our study, dexamethasone 4 mg given before
      laparoscopic cholecystectomy determined a significant decrease in plasma levels
      of sICAM-1. Both sICAM-1 and sVCAM-1 remained increased compared with baseline at
      24 hours in the C group. This may partially explain the postoperative anti
      inflammatory effects of dexamethasone. Further studies are needed.

PMID- 21877764
TI  - Pirlindole in the treatment of depression and fibromyalgia syndrome.
AB  - Depression and fibromyalgia syndrome are debilitating chronic conditions that
      impose a significant burden on individuals, families and society. Both depression
      and fibromyalgia have many overlapping symptoms, and antidepressants of several
      classes are among recommended treatment options for patients with fibromyalgia
      syndrome. Pirlindole is a selective and reversible inhibitor of monoamine oxidase
      (MAO) subtype A (MAO-A) that is approved in some European and non-European
      countries for the treatment of depression. The antidepressant efficacy and safety
      of pirlindole have been demonstrated in a number of placebo- and active
      comparator-controlled studies and are supported by many years of clinical
      experience in the treatment of depression. The drug's efficacy and safety have
      also been demonstrated, more recently, in the treatment of fibromyalgia syndrome.
      Pirlindole has a favourable tolerability profile, with no deleterious effect on
      cardiovascular dynamics. The effect of pirlindole on sensorimotor performance
      relevant to driving a motor vehicle is similar to that of placebo, as pirlindole
      appears to have an activating rather than a sedating antidepressant profile.
      Because of its specific and reversible inhibition of MAO-A and relatively short
      elimination half-life, no tyramine or 'cheese' effect is likely after short- or
      long-term administration. The available evidence supports pirlindole as a safe
      and effective treatment option for the management of depression and fibromyalgia
      syndrome.

PMID- 21877765
TI  - Effect of fluoxetine on the pharmacokinetics of lansoprazole: a two-treatment
      period study in healthy male subjects.
AB  - BACKGROUND: Fluoxetine is an inhibitor of the main metabolizing enzymes of
      lansoprazole and could influence the pharmacokinetics of lansoprazole. The
      changes in lansoprazole pharmacokinetics could have clinical significance
      concerning the safety of the therapy. OBJECTIVE: The aim of this study was to
      evaluate the pharmacokinetic interaction between fluoxetine and lansoprazole in
      healthy subjects. METHODS: A dose of lansoprazole 30 mg, alone or in combination
      with fluoxetine 60 mg, was administered to 18 healthy male subjects in a two
      treatment study design, separated by an 8-day period in which fluoxetine alone
      was administered as a single oral daily dose. Plasma concentrations of
      lansoprazole were determined during a 12-hour period following drug
      administration. Lansoprazole plasma concentrations were determined by a validated
      liquid chromatography-mass spectrometry method. The pharmacokinetic parameters of
      lansoprazole were calculated using non-compartmental analysis. RESULTS: In the
      two periods of treatment, the mean maximum plasma concentration (C(max)) values
      were 817 ng/mL (lansoprazole alone) and 1370 ng/mL (lansoprazole in combination
      with fluoxetine after pre-treatment with fluoxetine for 8 days) [p < 0.0001]. The
      observed area under the plasma concentration-time curve (AUC) from time zero to
      time of last measurable concentration values were 2400 and 6220 ng . h/mL (p <
      0.0001), respectively, and the AUC from time zero to infinity values were 2480
      and 7290 ng . h/mL (p < 0.0001), respectively. The time to reach C(max) values
      were 2.72 and 2.64 hours, respectively. The elimination rate constant from the
      central compartment values were 0.50 and 0.21 h-1, respectively (p < 0.0001). The
      elimination half-life values were 1.47 and 3.56 hours (p < 0.0001), respectively,
      and the mean residence times were 4.0 and 6.9 hours (p < 0.0001), respectively.
      CONCLUSION: The data demonstrate a pharmacokinetic interaction between fluoxetine
      and lansoprazole and suggest that the observed interaction may be clinically
      significant, although its clinical relevance has yet to be confirmed.

PMID- 21877766
TI  - Comparison of the pharmacokinetics of pitavastatin by formulation and ethnic
      group: an open-label, single-dose, two-way crossover pharmacokinetic study in
      healthy Caucasian and Japanese men.
AB  - BACKGROUND AND OBJECTIVES: Pitavastatin is a highly effective lipid-lowering drug
      (approved dose range 1-4 mg/day) with a distinctive metabolic pathway that has a
      low potential for drug interactions. The efficacy and safety of pitavastatin have
      been characterized in a broad clinical development programme conducted initially
      in Japanese patients. The objectives of the present study were to evaluate the
      pharmacokinetic bioequivalence of the European (EU) and Japanese (JP)
      formulations of pitavastatin 2 mg in healthy Japanese and Caucasian men, and to
      assess whether the bioavailability of each formulation was similar in the two
      ethnic groups. METHODS: In this open-label, single-dose, two-way crossover
      pharmacokinetic study, healthy men aged 18-45 years were randomized to receive:
      the JP formulation of pitavastatin 2 mg followed by the EU formulation; or the EU
      formulation of pitavastatin 2 mg followed by the JP formulation. The main outcome
      measures were maximum plasma concentration (C(max)), area under the plasma
      concentration-time curve (AUC) during a dosage interval (tau) [AUC(tau)] and AUC
      from time zero to infinity (AUC(infinity)) for pitavastatin and its main
      (inactive) metabolite pitavastatin lactone. Plasma concentrations of pitavastatin
      and pitavastatin lactone were determined using a validated liquid chromatography
      tandem mass spectrometry method. RESULTS: Forty-eight Caucasian and 12 Japanese
      men completed the study. Compared with the Japanese men, the Caucasian men were
      of greater mean body weight (76.1 vs 58.9 kg), height (180.8 vs 170.8 cm) and
      body mass index (23.2 vs 20.2 kg/m2). Geometric mean ratios (GMRs) of the
      pharmacokinetic parameters of pitavastatin demonstrated bioequivalence of the EU
      and JP formulations: GMRs and 90% confidence intervals (CIs) fell within the
      range 80-125% in Caucasian men and in Caucasian and Japanese groups combined for
      pitavastatin C(max) (combined analysis: GMR 103.1% [90% CI 96.0, 110.6]),
      AUC(tau) (GMR 99.6% [90% CI 95.5, 104.0]), and AUC(infinity) (GMR 104.2% [90% CI
      96.2, 112.8]). After adjusting for age and body weight in the pooled formulation
      analysis, bioequivalence between the Caucasian and Japanese groups was similarly
      demonstrated for pitavastatin C(max) (GMR 96.8% [90% CI 90.2, 103.8]), AUC(tau)
      (GMR 98.3% [90% CI 94.2, 102.7]) and AUC(infinity) (GMR 85.9% [90% CI 81.1,
      91.0]). CONCLUSION: The EU and JP formulations of pitavastatin showed
      pharmacokinetic bioequivalence, and there were no clinically relevant differences
      in exposure to pitavastatin between Caucasian and Japanese participants when
      differences in body weight were taken into account.

PMID- 21877767
TI  - Geoacoustic inversion in a dispersive waveguide using warping operators.
AB  - This paper presents a single receiver geoacoustic inversion method adapted for
      low-frequency impulsive sources. It is applied to light bulb data collected
      during the Shallow Water 2006 experiment. The inversion is carried out by
      extracting dispersion curves from the received signal, and comparing them to
      simulated replicas. To achieve dispersion curve estimation in the time-frequency
      domain, modal separability is improved using a signal processing method called
      warping. The inversion scheme allows for a reliable estimation of the New Jersey
      Shelf sediment properties (compressional sound speed and density). It also
      provides an accurate estimation of the source/receiver range.

PMID- 21877768
TI  - Perception of interrupted speech: cross-rate variation in the intelligibility of
      gated and concatenated sentences.
AB  - Temporal constraints on the perception of variable-size speech fragments produced
      by interruption rates between 0.5 and 16 Hz were investigated by contrasting the
      intelligibility of gated sentences with and without silent intervals.
      Concatenation of consecutive speech fragments produced a significant decrease in
      intelligibility at 2 and 4 Hz, while having little effect at lower and higher
      rates. Consistent with previous studies, these findings indicate that (1)
      syllable-sized intervals associated with intermediate-rate interruptions are more
      susceptible to temporal distortions than the longer word-size or shorter phoneme
      size intervals and (2) suggest qualitative differences in underlying perceptual
      processes at different rates.

PMID- 21877769
TI  - Importance of temporal-envelope speech cues in different spectral regions.
AB  - This study investigated the ability to use temporal-envelope (E) cues in a
      consonant identification task when presented within one or two frequency bands.
      Syllables were split into five bands spanning the range 70-7300 Hz with each band
      processed to preserve E cues and degrade temporal fine-structure cues.
      Identification scores were measured for normal-hearing listeners in quiet for
      individual processed bands and for pairs of bands. Consistent patterns of results
      were obtained in both the single- and dual-band conditions: identification scores
      increased systematically with band center frequency, showing that E cues in the
      higher bands (1.8-7.3 kHz) convey greater information.

PMID- 21877770
TI  - Propagation of two longitudinal waves in a cancellous bone with the closed pore
      boundary.
AB  - Ultrasound propagation in cancellous bone (porous media) under the condition of
      closed pore boundaries was investigated. A cancellous bone and two plate-like
      cortical bones obtained from a racehorse were prepared. A water-immersion
      ultrasound technique in the MHz range and a three-dimensional elastic finite
      difference time-domain (FDTD) method were used to investigate the waves. The
      experiments and simulations showed a clear separation of the incident
      longitudinal wave into fast and slow waves. The findings advance the evaluation
      of bones based on the two-wave phenomenon for in vivo assessment.

PMID- 21877771
TI  - Improvement of rotary encoders in human-machine-interfaces through optimized
      acoustic feedback.
AB  - This work investigates the effect of the acoustic feedback of rotary encoders
      that are common in current human-machine-interfaces. The results are based on
      subjective trials in which the probands had to complete generic tasks using an
      encoder with programmable electro acoustic feedback. The tasks had to be
      performed with individually optimized feedback and two reference conditions. The
      results of the investigation showed the advantage of well-defined acoustic
      feedback on both accuracy and speed of task fulfillment.

PMID- 21877772
TI  - Modeling manner of contact in the synthesis of impact sounds for perceptual
      research.
AB  - Impact sounds synthesized according to a physical model have increasingly become
      the stimulus of choice in studies of sound source perception. Few studies,
      however, have incorporated manner of contact in their models because of the
      complexity of the mechanics involved. Here a simplified model of contact is
      described suitable for application to perceptual research. The results of the
      simplified model are shown to be in good agreement with those of more
      comprehensive numerical methods receiving prior acoustic validation [Chaigne and
      Lambourg, J. Acoust. Soc. Am. 109, 1422-1432 (2001)]. The advantages of the model
      for applications to perceptual research are discussed.

PMID- 21877773
TI  - Ultrasonic anechoic chamber qualification: accounting for atmospheric absorption
      and transducer directivity.
AB  - Qualifying an anechoic chamber for frequencies that extend into the ultrasonic
      range is necessary for research work involving airborne ultrasonic sound. The
      ANSI S12.55/ISO 3745 standard which covers anechoic chamber qualification does
      not extend into the ultrasonic frequency range, nor have issues pertinent to this
      frequency range been fully discussed in the literature. An increasing number of
      technologies employ ultrasound; hence the need for an ultrasonic anechoic
      chamber. This paper will specifically discuss the need to account for atmospheric
      absorption and issues pertaining to source transducer directivity by presenting
      some results for qualification of a chamber at Brigham Young University.

PMID- 21877774
TI  - Striation-based beamforming for estimating the waveguide invariant with passive
      sonar.
AB  - The waveguide invariant summarizes the pattern of constructive and destructive
      interference between acoustic modes propagating in the ocean waveguide. For many
      sonar signal-processing schemes, it is essential to know the correct numerical
      value for the waveguide invariant. While conventional beamforming can estimate
      the ratio between the waveguide invariant and the range to the source, it cannot
      unambiguously separate the two terms. In the present work, striation-based
      beamforming is developed. It is shown that the striation-based beamformer can be
      used to produce an estimate for the waveguide invariant that is independent of
      the range. Simulation results are presented.

PMID- 21877775
TI  - Acquisition of detailed laryngeal flow measurements in geometrically realistic
      models.
AB  - Characterization of laryngeal flow velocity fields is important to understanding
      vocal fold vibration and voice production. One common method for acquiring flow
      field data is particle image velocimetry (PIV). However, because using PIV with
      models that have curved surfaces is problematic due to optical distortion,
      experimental investigations of laryngeal airflow are typically performed using
      models with idealized geometries. In this paper a method for acquiring PIV data
      using models with realistic geometries is presented. Sample subglottal,
      intraglottal, and supraglottal PIV data are shown. Capabilities and limitations
      are discussed, and suggestions for future implementation are provided.

PMID- 21877776
TI  - Bubble proliferation in the cavitation field of a shock wave lithotripter.
AB  - Lithotripter shock waves (SWs) generated in non-degassed water at 0.5 and 2 Hz
      pulse repetition frequency (PRF) were characterized using a fiber-optic
      hydrophone. High-speed imaging captured the inertial growth-collapse-rebound
      cycle of cavitation bubbles, and continuous recording with a 60 fps camcorder was
      used to track bubble proliferation over successive SWs. Microbubbles that seeded
      the generation of bubble clouds formed by the breakup of cavitation jets and by
      bubble collapse following rebound. Microbubbles that persisted long enough served
      as cavitation nuclei for subsequent SWs, as such bubble clouds were enhanced at
      fast PRF. Visual tracking suggests that bubble clouds can originate from single
      bubbles.

PMID- 21877777
TI  - Binaural benefit for speech recognition with spectral mismatch across ears in
      simulated electric hearing.
AB  - The present study investigated the effects of binaural spectral mismatch on
      binaural benefits in the context of bilateral cochlear implants using acoustic
      simulations. Binaural spectral mismatch was systematically manipulated by
      simulating changes in the relative insertion depths across ears. Sentence
      recognition, presented unilaterally and bilaterally, were measured in normal
      hearing listeners in quiet and noise at +5 dB signal-to-noise ratio. Significant
      binaural benefits were observed when the interaural difference in insertion depth
      was 1 mm or less. This result suggests a dependence of the binaural benefit on
      redundant speech information, rather than on similarity in performance across
      ears.

PMID- 21877778
TI  - Boundary effects on backscattering by a solid aluminum cylinder: experiment and
      finite element model comparisons (L).
AB  - Backscattering of sound by a solid aluminum cylinder was measured in the free
      field and with the cylinder near a flat surface. The target was suspended just
      below the surface of a water tank to simulate some aspects of backscattering when
      resting on the seabed. Measurements were compared with predictions made by an
      approximate hybrid approach based on multiple two-dimensional finite element
      calculations and the use of images. Many of the spectral features present in the
      tank data were present in the model. Comparing numerical model predictions with
      experimental data serves to build credibility for the modeling approach and can
      assist in developing insight into the underlying physical processes.

PMID- 21877779
TI  - Full scale model investigation on the acoustical protection of a balcony-like
      facade device (L).
AB  - The acoustical insertion losses produced by a balcony-like structure in front of
      a window are examined experimentally. The results suggest that the balcony
      ceiling is the most appropriate location for the installation of artificial sound
      absorption for the purpose of improving the broadband insertion loss, while the
      side walls are found to be the second best. Results also indicate that the
      acoustic modes of the balcony opening and the balcony cavity resonance in a
      direction normal to the window could have a great impact on the one-third octave
      band insertion losses. The maximum broadband road traffic noise insertion loss
      achieved is about 7 dB.

PMID- 21877780
TI  - Comment on "A field study of the exposure-annoyance relationship of military
      shooting noise" [J. Acoust. Soc. Am. 127, 2301-2311 (2010)] (L).

PMID- 21877781
TI  - Hearing thresholds of a harbor porpoise (Phocoena phocoena) for helicopter
      dipping sonar signals (1.43-1.33 kHz) (L).
AB  - Helicopter long range active sonar (HELRAS), a "dipping" sonar system used by
      lowering transducer and receiver arrays into water from helicopters, produces
      signals within the functional hearing range of many marine animals, including the
      harbor porpoise. The distance at which the signals can be heard is unknown, and
      depends, among other factors, on the hearing sensitivity of the species to these
      particular signals. Therefore, the hearing thresholds of a harbor porpoise for
      HELRAS signals were quantified by means of a psychophysical technique. Detection
      thresholds were obtained for five 1.25 s simulated HELRAS signals, varying in
      their harmonic content and amplitude envelopes. The 50% hearing thresholds for
      the different signals were similar: 76 dB re 1 MUPa (broadband sound pressure
      level, averaged over the signal duration). The detection thresholds were similar
      to those found in the same porpoise for tonal signals in the 1-2 kHz range
      measured in a previous study. Harmonic distortion, which occurred in three of the
      five signals, had little influence on their audibility. The results of this
      study, combined with information on the source level of the signal, the
      propagation conditions and ambient noise levels, allow the calculation of
      accurate estimates of the distances at which porpoises can detect HELRAS signals.

PMID- 21877782
TI  - The use of the virtual source technique in computing scattering from periodic
      ocean surfaces.
AB  - In this paper the virtual source technique is used to compute scattering of a
      plane wave from a periodic ocean surface. The virtual source technique is a
      method of imposing boundary conditions using virtual sources, with initially
      unknown complex amplitudes. These amplitudes are then determined by applying the
      boundary conditions. The fields due to these virtual sources are given by the
      environment Green's function. In principle, satisfying boundary conditions on an
      infinite surface requires an infinite number of sources. In this paper, the
      periodic nature of the surface is employed to populate a single period of the
      surface with virtual sources and m surface periods are added to obtain scattering
      from the entire surface. The use of an accelerated sum formula makes it possible
      to obtain a convergent sum with relatively small number of terms (~40). The
      accuracy of the technique is verified by comparing its results with those
      obtained using the integral equation technique.

PMID- 21877783
TI  - Edge resonance and zero group velocity Lamb modes in a free elastic plate.
AB  - The local resonances of a free isotropic elastic plate are investigated using
      laser ultrasonic techniques. Experimental results are interpreted in terms of
      zero group velocity Lamb modes and edge mode. At a distance from the edge larger
      than the plate thickness a sharp resonance is observed at the frequency where the
      group velocity of the first symmetrical Lamb mode vanishes. Close to the edge of
      the plate, the resonance due to the edge mode dominates. Both zero group velocity
      and edge resonances appear at the theoretically predicted frequencies. These
      frequencies do not vary with the distance from the edge of the plate and the
      transition between the two modes of vibration, at about the plate thickness, is
      abrupt. Using a laser excitation on the edge, the amplitude profile of the normal
      displacement at the edge resonance frequency was determined.

PMID- 21877784
TI  - Acoustic attenuation, phase and group velocities in liquid-filled pipes II:
      simulation for Spallation Neutron Sources and planetary exploration.
AB  - This paper uses a finite element method (FEM) to compare predictions of the
      attenuation and sound speeds of acoustic modes in a fluid-filled pipe with those
      of the analytical model presented in the first paper in this series. It explains
      why, when the predictions of the earlier paper were compared with experimental
      data from a water-filled PMMA pipe, the uncertainties and agreement for
      attenuation data were worse than those for sound speed data. Having validated the
      FEM approach in this way, the versatility of FEM is thereafter demonstrated by
      modeling two practical applications which are beyond the analysis of the earlier
      paper. These applications model propagation in the mercury-filled steel pipework
      of the Spallation Neutron Source at the Oak Ridge National Laboratory
      (Tennessee), and in a long-standing design for acoustic sensors for use on
      planetary probes. The results show that strong coupling between the fluid and the
      solid walls means that erroneous interpretations are made of the data if they
      assume that the sound speed and attenuation in the fluid in the pipe are the same
      as those that would be measured in an infinite volume of identical fluid,
      assumptions which are common when such data have previously been interpreted.

PMID- 21877785
TI  - On observing acoustic backscattering from salinity turbulence.
AB  - It has been hypothesized that at sufficiently high levels of oceanic salinity
      turbulence it should be possible to observe acoustic backscattering. However,
      there have been limited in situ measurements to confirm this hypothesis. Using an
      autonomous underwater vehicle equipped with upward and downward looking 1.2 MHz
      acoustic Doppler current profilers and with turbulence and fine scale sensors,
      measurements were performed in a region of intense turbulence and a strong
      salinity gradient. The approach taken was to correlate variations in the
      backscattered acoustic intensity, I, with a theoretical acoustic backscattering
      cross section per volume for salinity turbulence, sigma(s), to obtain an
      estimated scattering cross section per volume, sigma(e). Results indicated that
      of order 50% of the observed region was characterized by salinity turbulence
      induced backscattering.

PMID- 21877786
TI  - Adaptive projection method applied to three-dimensional ultrasonic focusing and
      steering through the ribs.
AB  - An adaptive projection method for ultrasonic focusing through the rib cage, with
      minimal energy deposition on the ribs, was evaluated experimentally in 3D
      geometry. Adaptive projection is based on decomposition of the time-reversal
      operator (DORT method) and projection on the "noise" subspace. It is shown that
      3D implementation of this method is straightforward, and not more time-consuming
      than 2D. Comparisons are made between adaptive projection, spherical focusing,
      and a previously proposed time-reversal focusing method, by measuring pressure
      fields in the focal plane and rib region using the three methods. The ratio of
      the specific absorption rate at the focus over the one at the ribs was found to
      be increased by a factor of up to eight, versus spherical emission. Beam steering
      out of geometric focus was also investigated. For all configurations projecting
      steered emissions were found to deposit less energy on the ribs than steering
      time-reversed emissions: thus the non-invasive method presented here is more
      efficient than state-of-the-art invasive techniques. In fact, this method could
      be used for real-time treatment, because a single acquisition of back-scattered
      echoes from the ribs is enough to treat a large volume around the focus, thanks
      to real time projection of the steered beams.

PMID- 21877787
TI  - Modeling and validation of polyurethane based passive underwater acoustic
      absorber.
AB  - The acoustic behavior of an acoustically transparent polyurethane and an
      interpenetrating polymer network of polyurethane with polydimethyl siloxane were
      studied using dynamic mechanical analysis, finite element modeling, and
      experimental evaluation of acoustic properties in a water-filled pulse tube
      setup. Dynamic mechanical measurements in the temperature range -50  degrees C to
      +70  degrees C were carried out, and the data were used for time temperature
      superposition to generate material behavior at high frequencies. These inputs
      were used for modeling the acoustic behavior of these materials using ATILA,
      which is a commercial finite element code, capable of computing transmission and
      reflection characteristics of materials. From this data, absorption
      characteristics were computed. The results were compared with the experimental
      results obtained using a water-filled pulse tube facility.

PMID- 21877788
TI  - Analysis and localization of blue whale vocalizations in the Solomon Sea using
      waveform amplitude data.
AB  - During the Woodlark Basin seismic experiment in eastern Papua New Guinea (1999
      2000), an ocean-bottom seismic array recorded marine mammal vocalizations along
      with target earthquake signals. The array consisted of 14 instruments, 7 of which
      were three-component seismometers with a fourth component hydrophone. They were
      deployed at 2.0-3.2 km water depth and operated from September 1999 through
      February 2000. While whale vocalizations were recorded throughout the deployment,
      this study focuses on 3 h from December 21, 1999 during which the signals are
      particularly clear. The recordings show a blue whale song composed of a three
      unit phrase. That song does not match vocalization characteristics of other known
      Pacific subpopulations and may represent a previously undocumented blue whale
      song. Animal tracking and source level estimates are obtained with a Bayesian
      inversion method that generates probabilistic source locations. The Bayesian
      method is augmented to include travel time estimates from seismometers and
      hydrophones and acoustic signal amplitude. Tracking results show the whale
      traveled northeasterly over the course of 3 h, covering approximately 27 km. The
      path followed the edge of the Woodlark Basin along a shelf that separates the
      shallow waters of the Trobriand platform from the deep waters of the basin.

PMID- 21877789
TI  - Absolute backscatter coefficient estimates of tissue-mimicking phantoms in the 5
      50 MHz frequency range.
AB  - Absolute backscatter coefficients in tissue-mimicking phantoms were
      experimentally determined in the 5-50 MHz frequency range using a broadband
      technique. A focused broadband transducer from a commercial research system, the
      VisualSonics Vevo 770, was used with two tissue-mimicking phantoms. The phantoms
      differed regarding the thin layers covering their surfaces to prevent desiccation
      and regarding glass bead concentrations and diameter distributions. Ultrasound
      scanning of these phantoms was performed through the thin layer. To avoid signal
      saturation, the power spectra obtained from the backscattered radio frequency
      signals were calibrated by using the signal from a liquid planar reflector, a
      water-brominated hydrocarbon interface with acoustic impedance close to that of
      water. Experimental values of absolute backscatter coefficients were compared
      with those predicted by the Faran scattering model over the frequency range 5-50
      MHz. The mean percent difference and standard deviation was 54% +/- 45% for the
      phantom with a mean glass bead diameter of 5.40 MUm and was 47% +/- 28% for the
      phantom with 5.16 MUm mean diameter beads.

PMID- 21877790
TI  - Semicylindrical acoustic transducer from a dielectric elastomer film with
      compliant electrodes.
AB  - A semicylindrical acoustic transducer was constructed using a dielectric
      elastomer film with compliant electrodes that is an electroactive polymer
      composed of a polyurethane elastomer base and polyethylene
      dioxythiophene/polystyrene sulfonate electrodes. The use of this dielectric
      elastomer is advantageous because polyurethane is a common material that keeps
      its shape without any rigid frame. Because the dielectric elastomer films are
      essentially incompressible, electric-field-induced thickness changes are usually
      translated into much larger changes of the film area and side length. Here it is
      proposed that this change in side length can be utilized for sound generation
      when the film is bent into a semicylindrical shape. Accordingly, a
      semicylindrical acoustic transducer was fabricated using a film of thickness of
      300 MUm and its acoustic characteristics were investigated. The transducer can be
      operated at low applied voltages by reducing the film thickness, as long as the
      film is thick enough to generate sufficient force to overcome sound radiation
      impedance. The second harmonic distortion of the transducer was also investigated
      as a function of the ratio of the direct current bias voltage to the alternating
      current audio signal amplitude.

PMID- 21877791
TI  - Modal analysis of the electromechanical conversion in piezoelectric ceramic
      spherical shells.
AB  - The current study considers piezoelectric ceramic electromechanical transducers
      utilizing axisymmetric vibrations of complete and incomplete spherical shells.
      Analysis is focused on generating the modes of vibration that can be employed in
      the design of multimode unidirectional electroacoustic transducers for underwater
      applications and on determining the electrode configurations that achieve optimal
      electromechanical coupling for the different modes of vibration considered.
      Analytical expressions are presented for the modal and intermodal equivalent
      parameters characterizing the energy state of the shell vibration. Results of
      calculation and experimental verification of the resonance frequencies and
      effective coupling coefficients for different modes of vibration of the complete
      and incomplete spherical shells are in good agreement.

PMID- 21877792
TI  - Numerical and asymptotic approach for evaluating complex wavenumbers of guided
      modes in viscoelastic plates.
AB  - The approximate description of the dispersion curves is obtained using
      asymptotics of complex wavenumbers for different boundary conditions on the plate
      surfaces. Their comparison with the exact results shows satisfactory agreement.
      This approach provides an algorithm to evaluate the infinite spectrum of non
      propagating modes more easily and numerically stable even for wavenumbers of big
      values. Results are verified by the alternative semianalytical finite element
      method, which also supplies the mode shapes for better identification and
      classification.

PMID- 21877793
TI  - Single frequency sound propagation in flat waveguides with locally reactive
      impedance boundaries.
AB  - A coherent image source method is presented for evaluating single frequency sound
      propagation from a point source in a flat waveguide with two infinite and
      parallel locally reactive boundaries. The method starts from formulating
      reflections of the spherical sound radiation into integrals of plane wave
      expansion, and the analytical evaluation of the integrals is simplified by
      introducing a physically plausible assumption that wave front shapes remain the
      same before and after each reflection on a reflective boundary. The proposed
      model can determine coherently the sound fields at arbitrary receiver locations
      in a flat waveguide, even when one boundary is highly sound absorptive. Being
      compared with the classical wave theory and the existing coherent ray-based
      methods, it is shown that the proposed method provides considerable accuracy and
      advantages to predict sound propagation in flat waveguides with a sound
      absorptive ceiling and a reflective floor over a broad frequency range,
      particularly at large distances from the source where the existing methods are
      problematic.

PMID- 21877794
TI  - The effects of elastic supports on the transient vibroacoustic response of a
      window caused by sonic booms.
AB  - The transient vibration and sound radiation (TVSR) of plate-like structures with
      general elastic boundary conditions was investigated using the time-domain finite
      element method (TDFEM) and time-domain boundary element method (TDBEM). In this
      model, the structure can have arbitrary elastic boundary conditions and hence the
      effects of the boundary conditions on the TVSR can be effectively studied. The
      predicted results agreed well with existing experimental data using two classical
      boundary conditions: simply supported at all edges and clamped-free-free-free.
      The TVSR of a single panel with a more general boundary condition in two
      connected chambers was also measured. The predicted results agreed well with
      these experimental results. The prediction method was subsequently applied to
      evaluate the effects of elastic boundary supports on the TVSR of a window caused
      by a sonic boom. Loudness, non-audible acoustic perception, and tactile vibration
      thresholds were analyzed for different boundary conditions (varying between
      clamped and simply supported). The possibility of improving the transient
      vibration and noise isolation performance by selecting an appropriate boundary
      condition was thereby demonstrated.

PMID- 21877795
TI  - A first-principles model for estimating the prevalence of annoyance with aircraft
      noise exposure.
AB  - Numerous relationships between noise exposure and transportation noise-induced
      annoyance have been inferred by curve-fitting methods. The present paper develops
      a different approach. It derives a systematic relationship by applying an a
      priori, first-principles model to the findings of forty three studies of the
      annoyance of aviation noise. The rate of change of annoyance with day-night
      average sound level (DNL) due to aircraft noise exposure was found to closely
      resemble the rate of change of loudness with sound level. The agreement of model
      predictions with the findings of recent curve-fitting exercises (cf. Miedma and
      Vos, 1998) is noteworthy, considering that other analyses have relied on
      different analytic methods and disparate data sets. Even though annoyance
      prevalence rates within individual communities consistently grow in proportion to
      duration-adjusted loudness, variability in annoyance prevalence rates across
      communities remains great. The present analyses demonstrate that 1) community
      specific differences in annoyance prevalence rates can be plausibly attributed to
      the joint effect of acoustic and non-DNL related factors and (2) a simple model
      can account for the aggregate influences of non-DNL related factors on annoyance
      prevalence rates in different communities in terms of a single parameter
      expressed in DNL units-a "community tolerance level."

PMID- 21877796
TI  - Acoustic analysis of a rectangular cavity with general impedance boundary
      conditions.
AB  - A Fourier series method is proposed for the acoustic analysis of a rectangular
      cavity with impedance boundary conditions arbitrarily specified on any of the
      walls. The sound pressure is expressed as the combination of a three-dimensional
      Fourier cosine series and six supplementary two-dimensional expansions introduced
      to ensure (accelerate) the uniform and absolute convergence (rate) of the series
      representation in the cavity including the boundary surfaces. The expansion
      coefficients are determined using the Rayleigh-Ritz method. Since the pressure
      field is constructed adequately smooth throughout the entire solution domain, the
      Rayleigh-Ritz solution is mathematically equivalent to what is obtained from a
      strong formulation based on directly solving the governing equations and the
      boundary conditions. To unify the treatments of arbitrary nonuniform impedance
      boundary conditions, the impedance distribution function on each specified
      surface is invariantly expressed as a double Fourier series expansion so that all
      the relevant integrals can be calculated analytically. The modal parameters for
      the acoustic cavity can be simultaneously obtained from solving a standard matrix
      eigenvalue problem instead of iteratively solving a nonlinear transcendental
      equation as in the existing methods. Several numerical examples are presented to
      demonstrate the effectiveness and reliability of the current method for various
      impedance boundary conditions, including nonuniform impedance distributions.

PMID- 21877797
TI  - Influence of static compression on mechanical parameters of acoustic foams.
AB  - The modification of elastic properties of compressed acoustic foams is
      investigated. The porous sample is first submitted to a static compression and
      then to a dynamic excitation of smaller amplitude, corresponding to acoustical
      applications. The static compression induces the modification of the dynamic
      elastic parameters of the material. This work focuses on Young's modulus. The
      variation is measured with two different experimental methods: The classical
      rigidimeter and an absorption measurement. The effective Young's modulus is
      directly measured with the first method and is indirectly determined through the
      quarter-wave length resonance of the frame with the second one. The results of
      the two measurements are compared and give similar tendencies. The variation of
      the dynamic Young's modulus as a function of the degree of compression of the
      sample is shown to be separated in several zones. In the zones associated with
      weak compression (those usually zones encountered in practice), the variation of
      the effective Young's modulus can be approximated by a simple affine function.
      The results are compared for different foams. A simple model of the dependency of
      the Young's modulus with respect to the static degree of compression is finally
      proposed for weak compressions.

PMID- 21877798
TI  - Computation of acoustic absorption in media composed of packed microtubes
      exhibiting surface irregularity.
AB  - A multi-scale homogenization technique and a finite element-based solution
      procedure are employed to compute acoustic absorption in smooth and rough packed
      microtubes. The absorption considered arises from thermo-viscous interactions
      between the fluid media and the microtube walls. The homogenization technique
      requires geometric periodicity, which for smooth tubes is invoked using the
      periodicity of the finite element mesh; for rough microtubes, the periodicity
      invoked is that associated with the roughness. Analysis of the packed
      configurations, for the specific microtube radii considered, demonstrates that
      surface roughness does not appreciably increase the overall absorption, but
      instead shifts the peaks and values of the absorption curve. Additionally, the
      effect of the fluid media temperature on acoustic absorption is also explored.
      The results of the investigation are used to make conclusions about tailored
      design of acoustically absorbing microtube-based materials.

PMID- 21877800
TI  - Time delay and Doppler estimation for wideband acoustic signals in multipath
      environments.
AB  - Estimation of the parameters of a multipath underwater acoustic channel is of
      great interest for a variety of applications. This paper proposes a high
      resolution method for jointly estimating the multipath time delays, Doppler
      scales, and attenuation amplitudes of a time-varying acoustical channel. The
      proposed method formulates the estimation of channel parameters into a sparse
      representation problem. With the [script-l](1)-norm as the measure of sparsity,
      the proposed method makes use of the basis pursuit (BP) criterion to find the
      sparse solution. The ill-conditioning can be effectively reduced by the [script
      l](1)-norm regularization. Unlike many existing methods that are only applicable
      to narrowband signals, the proposed method can handle both narrowband and
      wideband signals. Simulation results are provided to verify the performance and
      effectiveness of the proposed algorithm, indicating that it has a super
      resolution in both delay and Doppler domain, and it is robust to noise.

PMID- 21877799
TI  - Concert hall acoustics assessment with individually elicited attributes.
AB  - Concert hall acoustics was evaluated with a descriptive sensory analysis method
      by employing an individual vocabulary development technique. The goal was to
      obtain sensory profiles of three concert halls by eliciting perceptual attributes
      for evaluation and comparison of the halls. The stimuli were gathered by playing
      back anechoic symphony music from 34 loudspeakers on stage in each concert hall
      and recording the sound field with a microphone array. Four musical programs were
      processed for multichannel 3D sound reproduction in the actual listening test.
      Twenty screened assessors developed their individual set of attributes and
      performed a comparative evaluation of nine seats, three in each hall. The results
      contain the distinctive groups of elicited attributes and show good agreement
      within assessors, even though they applied individual attributes when rating the
      samples. It was also found that loudness and distance gave the strongest
      perceptual direction to the principal component basis. In addition, the study
      revealed that the perception of reverberance is related to the size of the space
      or to the enveloping reverberance, depending on the assessor.

PMID- 21877801
TI  - Ipsilateral masking between acoustic and electric stimulations.
AB  - Residual acoustic hearing can be preserved in the same ear following cochlear
      implantation with minimally traumatic surgical techniques and short-electrode
      arrays. The combined electric-acoustic stimulation significantly improves
      cochlear implant performance, particularly speech recognition in noise. The
      present study measures simultaneous masking by electric pulses on acoustic pure
      tones, or vice versa, to investigate electric-acoustic interactions and their
      underlying psychophysical mechanisms. Six subjects, with acoustic hearing
      preserved at low frequencies in their implanted ear, participated in the study.
      One subject had a fully inserted 24 mm Nucleus Freedom array and five subjects
      had Iowa/Nucleus hybrid implants that were only 10 mm in length. Electric masking
      data of the long-electrode subject showed that stimulation from the most apical
      electrodes produced threshold elevations over 10 dB for 500, 625, and 750 Hz
      probe tones, but no elevation for 125 and 250 Hz tones. On the contrary, electric
      stimulation did not produce any electric masking in the short-electrode subjects.
      In the acoustic masking experiment, 125-750 Hz pure tones were used to
      acoustically mask electric stimulation. The acoustic masking results showed that,
      independent of pure tone frequency, both long- and short-electrode subjects
      showed threshold elevations at apical and basal electrodes. The present results
      can be interpreted in terms of underlying physiological mechanisms related to
      either place-dependent peripheral masking or place-independent central masking.

PMID- 21877802
TI  - Isolating mechanisms that influence measures of the precedence effect:
      theoretical predictions and behavioral tests.
AB  - This study tests how peripheral auditory processing and spectral dominance impact
      lateralization of precedence effect (PE) stimuli consisting of a pair of leading
      and lagging clicks. Predictions from a model whose parameters were set from
      established physiological results were tested with specific behavioral
      experiments. To generate predictions, an auditory nerve model drove a binaural,
      cross correlation computation whose outputs were summed across frequency using
      weightings derived from past physiological studies. The model predicted that
      lateralization (1) depends on stimulus center frequency and the inter-stimulus
      delay (ISD) between leading and lagging clicks for narrowband clicks and (2)
      changes differently with lead click level for different ISDs. Behaviorally,
      subjects lateralized narrowband and wideband click pairs whose stimulus
      parameters were chosen based on modeling results to test how peripheral
      processing and frequency dominance contribute to lateralization of PE stimuli.
      Behavioral results (including unique measures with the lead attenuated relative
      to the lag) suggest that peripheral interactions between leading and lagging
      clicks on the basilar membrane and strong weighting of cues around 750 Hz
      influence lateralization of paired clicks with short ISDs. When combined with
      auditory nerve adaptation, which emphasizes onset information, lateralization of
      PE click pairs with a short ISD can be well predicted.

PMID- 21877803
TI  - The role of masker fringes for the detection of coherent tone pips.
AB  - Three experiments investigated the role of pre/post exposure to a masker in a
      detection task with complex, random, spectro-temporal maskers. In the first
      experiment, the masker was either continuously presented or pulsed on and off
      with the signal. For most listeners, thresholds were lower when the masker was
      continuously presented, despite the fact that there was more uncertainty about
      the timing of the signal. In the second experiment, the signal-bearing portion of
      the masker was preceded and followed by masker "fringes" of different durations.
      Consistent with the findings of Experiment 1, for some listeners shorter-duration
      fringes led to higher thresholds than long-duration fringes. In the third
      experiment, the masker fringe (a) preceded, (b) followed, or (c) both preceded
      and followed, the signal. Relative to the middle signal conditions, a late signal
      yielded lower thresholds and the early signal yielded higher thresholds. These
      results indicate that listeners can use features of an ongoing sound to extract
      an added signal and that listeners differ in the importance of pre-exposure for
      efficient signal extraction. However, listeners do not appear to perform this
      comparison retrospectively after the signal, potentially indicating a form of
      backward masking.

PMID- 21877804
TI  - An adaptive filter-based method for robust, automatic detection and frequency
      estimation of whistles.
AB  - This paper proposes an adaptive filter-based method for detection and frequency
      estimation of whistle calls, such as the calls of birds and marine mammals, which
      are typically analyzed in the time-frequency domain using a spectrogram. The
      approach taken here is based on adaptive notch filtering, which is an established
      technique for frequency tracking. For application to automatic whistle
      processing, methods for detection and improved frequency tracking through
      frequency crossings as well as interfering transients are developed and coupled
      to the frequency tracker. Background noise estimation and compensation is
      accomplished using order statistics and pre-whitening. Using simulated signals as
      well as recorded calls of marine mammals and a human whistled speech utterance,
      it is shown that the proposed method can detect more simultaneous whistles than
      two competing spectrogram-based methods while not reporting any false alarms on
      the example datasets. In one example, it extracts complete 1.4 and 1.8 s
      bottlenose dolphin whistles successfully through frequency crossings. The method
      performs detection and estimates frequency tracks even at high sweep rates. The
      algorithm is also shown to be effective on human whistled utterances.

PMID- 21877805
TI  - Sequential streaming due to manipulation of interaural time differences.
AB  - The effect of apparent spatial location on sequential streaming was investigated
      by manipulating interaural time differences (ITDs). The degree of obligatory
      stream segregation was inferred indirectly from the threshold for detecting a
      rhythmic irregularity in an otherwise isochronous sequence of interleaved "A" and
      "B" tones. Stimuli were bandpass-filtered harmonic complexes with a 100-Hz
      fundamental. The A and B tones had equal but opposite ITDs of 0, 0.25, 0.5, 1, or
      2 ms and had the same or different passbands. The passband ranges were 1250-2500
      Hz and 1768-3536 Hz in experiment 1, and 353-707 Hz and 500-1000 Hz in experiment
      2. In both experiments, increases in ITD led to increases in threshold, mainly
      when the passbands of A and B were the same. The effects were largest for ITDs
      above 0.5 ms, for which rhythmic irregularities in the timing of the A or B tones
      alone may have disrupted performance. It is concluded that the differences in
      apparent spatial location produced by ITD have only weak effects on obligatory
      streaming.

PMID- 21877806
TI  - Temporal masking functions for listeners with real and simulated hearing loss.
AB  - A functional simulation of hearing loss was evaluated in its ability to reproduce
      the temporal masking functions for eight listeners with mild to severe
      sensorineural hearing loss. Each audiometric loss was simulated in a group of age
      matched normal-hearing listeners through a combination of spectrally-shaped
      masking noise and multi-band expansion. Temporal-masking functions were obtained
      in both groups of listeners using a forward-masking paradigm in which the level
      of a 110-ms masker required to just mask a 10-ms fixed-level probe (5-10 dB SL)
      was measured as a function of the time delay between the masker offset and probe
      onset. At each of four probe frequencies (500, 1000, 2000, and 4000 Hz), temporal
      masking functions were obtained using maskers that were 0.55, 1.0, and 1.15 times
      the probe frequency. The slopes and y-intercepts of the masking functions were
      not significantly different for listeners with real and simulated hearing loss.
      The y-intercepts were positively correlated with level of hearing loss while the
      slopes were negatively correlated. The ratio of the slopes obtained with the low
      frequency maskers relative to the on-frequency maskers was similar for both
      groups of listeners and indicated a smaller compressive effect than that observed
      in normal-hearing listeners.

PMID- 21877807
TI  - Study on the applicability of instrumental measures for black-box evaluation of
      static feedback control in hearing aids.
AB  - Presented is a report on black-box evaluation of feedback control systems for
      commercial hearing aids. The aim of the study is to examine the ability of
      existing instrumental measures to quantify the performance of the feedback
      control system in black-box settings and on realistic signals, when more than one
      element of the signal processing chain may be active (compression, noise
      suppression, microphone directionality, etc.). The evaluation is carried out on 6
      different hearing aids and for 10 measures. Thereby it is possible to see which
      measure is best suited to measuring which specific characteristic of the feedback
      control system, and serves as a beginning for conducting perceptual tests. The
      study uses static (but variable) feedback paths and is based on signals recorded
      from the in-ear microphone of an artificial head, on which the hearing
      instruments are mounted.

PMID- 21877808
TI  - Computation of physiological human vocal fold parameters by mathematical
      optimization of a biomechanical model.
AB  - With the use of an endoscopic, high-speed camera, vocal fold dynamics may be
      observed clinically during phonation. However, observation and subjective
      judgment alone may be insufficient for clinical diagnosis and documentation of
      improved vocal function, especially when the laryngeal disease lacks any clear
      morphological presentation. In this study, biomechanical parameters of the vocal
      folds are computed by adjusting the corresponding parameters of a three
      dimensional model until the dynamics of both systems are similar. First, a
      mathematical optimization method is presented. Next, model parameters (such as
      pressure, tension and masses) are adjusted to reproduce vocal fold dynamics, and
      the deduced parameters are physiologically interpreted. Various combinations of
      global and local optimization techniques are attempted. Evaluation of the
      optimization procedure is performed using 50 synthetically generated data sets.
      The results show sufficient reliability, including 0.07 normalized error, 96%
      correlation, and 91% accuracy. The technique is also demonstrated on data from
      human hemilarynx experiments, in which a low normalized error (0.16) and high
      correlation (84%) values were achieved. In the future, this technique may be
      applied to clinical high-speed images, yielding objective measures with which to
      document improved vocal function of patients with voice disorders.

PMID- 21877810
TI  - Assessment of local vocal fold deformation characteristics in an in vitro static
      tensile test.
AB  - Voice quality is strongly dependent on vocal fold dynamics, which in turn are
      dependent on lung pressure and vocal fold biomechanics. Numerical and physical
      models are often used to investigate the interactions of these different
      subsystems. However, the utility of numerical and physical models is limited
      unless appropriately validated with data from physiological models. Hence a
      method that enables analysis of local vocal fold deformations along the entire
      surface is presented. In static tensile tests, forces are applied to distinctive
      working points being located in cover and muscle, respectively, so that specific
      layer properties can be investigated. The forces are directed vertically upward
      and are applied along or above the vocal fold edge. The resulting deformations
      are analyzed using multiple perspectives and three-dimensional reconstruction.
      Deformation characteristics of four human vocal folds were investigated.
      Preliminary results showed two phases of deformation: a range with a small slope
      for small deformations fading into a significant nonlinear deformation trend with
      a high slope. An increase of tissue stiffness from posterior to anterior was
      detected. This trend is more significant for muscle and in the mid-anterior half
      of the vocal fold.

PMID- 21877809
TI  - Sensitivity of vocal fold vibratory modes to their three-layer structure:
      implications for computational modeling of phonation.
AB  - The sensitivity of the eigenmodes and eigenfrequencies of the human vocal fold to
      its three-layer structure is studied using finite-element modeling. The study
      covers a variety of three-dimensional vocal fold models ranging from an
      idealized, longitudinally uniform structure to a physiologically more realistic,
      longitudinally varying structure. Geometric parameters including the thickness of
      the ligament and cover layers as well as the ligament length are varied
      systematically. The results indicate that vocal fold vibratory modes are quite
      insensitive to the longitudinal variation in the thickness of the three layers as
      well as the variation in ligament length. However, significant overall changes in
      thickness of each layer can produce noticeable changes in these modes. The
      implications of these findings on computational modeling of phonation are
      discussed.

PMID- 21877811
TI  - Extending the articulation index to account for non-linear distortions introduced
      by noise-suppression algorithms.
AB  - The conventional articulation index (AI) measure cannot be applied in situations
      where non-linear operations are involved and additive noise is present. This is
      because the definitions of the target and masker signals become vague following
      non-linear processing, as both the target and masker signals are affected. The
      aim of the present work is to modify the basic form of the AI measure to account
      for non-linear processing. This was done using a new definition of the output or
      effective SNR obtained following non-linear processing. The proposed output SNR
      definition for a specific band was designed to handle cases where the non-linear
      processing affects predominantly the target signal rather than the masker signal.
      The proposed measure also takes into consideration the fact that the input SNR in
      a specific band cannot be improved following any form of non-linear processing.
      Overall, the proposed measure quantifies the proportion of input band SNR
      preserved or transmitted in each band after non-linear processing. High
      correlation (r = 0.9) was obtained with the proposed measure when evaluated with
      intelligibility scores obtained by normal-hearing listeners in 72 noisy
      conditions involving noise-suppressed speech corrupted in four different real
      world maskers.

PMID- 21877812
TI  - The influence of spectral characteristics of early reflections on speech
      intelligibility.
AB  - The auditory system takes advantage of early reflections (ERs) in a room by
      integrating them with the direct sound (DS) and thereby increasing the effective
      speech level. In the present paper the benefit from realistic ERs on speech
      intelligibility in diffuse speech-shaped noise was investigated for normal
      hearing and hearing-impaired listeners. Monaural and binaural speech
      intelligibility tests were performed in a virtual auditory environment where the
      spectral characteristics of ERs from a simulated room could be preserved. The
      useful ER energy was derived from the speech intelligibility results and the
      efficiency of the ERs was determined as the ratio of the useful ER energy to the
      total ER energy. Even though ER energy contributed to speech intelligibility, DS
      energy was always more efficient, leading to better speech intelligibility for
      both groups of listeners. The efficiency loss for the ERs was mainly ascribed to
      their altered spectrum compared to the DS and to the filtering by the torso,
      head, and pinna. No binaural processing other than a binaural summation effect
      could be observed.

PMID- 21877813
TI  - Effects of fundamental frequency and vocal-tract length cues on sentence
      segregation by listeners with hearing loss.
AB  - The purpose was to determine the effect of hearing loss on the ability to
      separate competing talkers using talker differences in fundamental frequency (F0)
      and apparent vocal-tract length (VTL). Performance of 13 adults with hearing loss
      and 6 adults with normal hearing was measured using the Coordinate Response
      Measure. For listeners with hearing loss, the speech was amplified and filtered
      according to the NAL-RP hearing aid prescription. Target-to-competition ratios
      varied from 0 to 9 dB. The target sentence was randomly assigned to the higher or
      lower values of F0 or VTL on each trial. Performance improved for F0 differences
      up to 9 and 6 semitones for people with normal hearing and hearing loss,
      respectively, but only when the target talker had the higher F0. Recognition for
      the lower F0 target improved when trial-to-trial uncertainty was removed (9
      semitone condition). Scores improved with increasing differences in VTL for the
      normal-hearing group. On average, hearing-impaired listeners did not benefit from
      VTL cues, but substantial inter-subject variability was observed. The amount of
      benefit from VTL cues was related to the average hearing loss in the 1-3-kHz
      region when the target talker had the shorter VTL.

PMID- 21877814
TI  - Method for measuring violin sound radiation based on bowed glissandi and its
      application to sound synthesis.
AB  - This work presents a method for measuring and computing violin-body directional
      frequency responses, which are used for violin sound synthesis. The approach is
      based on a frame-weighted deconvolution of excitation and response signals. The
      excitation, consisting of bowed glissandi, is measured with piezoelectric
      transducers built into the bridge. Radiation responses are recorded in an
      anechoic chamber with multiple microphones placed at different angles around the
      violin. The proposed deconvolution algorithm computes impulse responses that,
      when convolved with any source signal (captured with the same transducer),
      produce a highly realistic violin sound very similar to that of a microphone
      recording. The use of motion sensors allows for tracking violin movements.
      Combining this information with the directional responses and using a dynamic
      convolution algorithm, helps to improve the listening experience by incorporating
      the violinist motion effect in stereo.

PMID- 21877815
TI  - Evaluation of the echolocation model for range estimation of multiple closely
      spaced objects.
AB  - Experimental evidence indicates that bats can use frequency-modulated
      echolocation to identify objects with an accuracy of less than 1 MUs. However,
      when modeling this process, it is difficult to estimate the delay times of
      multiple closely spaced objects by analyzing the echo spectrum, because the
      sequence of delay separations cannot be determined without information on the
      temporal changes in the interference patterns of the echoes. To extract the
      temporal changes, Gaussian chirplets with a carrier frequency compatible with bat
      emission sweep rates are introduced. The delay time for object 1 (T(1)) is
      estimated from the echo spectrum around the onset time. The T(2) is obtained by
      adding the T(1) to the delay separation between objects 1 and 2. Further objects
      are located in sequence by this procedure. Here echoes were measured from single
      and multiple objects at a low signal-to-noise ratio. It was confirmed that the
      delay time for a single object could be estimated with an accuracy of about 1.3
      MUs. The range accuracy was less than 6 MUs when the frequency bandwidth was less
      than 10 kHz. The delay time for multiple closely spaced objects could be
      estimated with a high range resolution by extracting the interference pattern.

PMID- 21877816
TI  - Dolphin and sea lion auditory evoked potentials in response to single and
      multiple swept amplitude tones.
AB  - Measurement of the auditory steady-state response (ASSR) is increasingly used to
      assess marine mammal hearing. These tests normally entail measuring the ASSR to a
      sequence of sinusoidally amplitude modulated tones, so that the ASSR amplitude
      function can be defined and the auditory threshold estimated. In this study, an
      alternative method was employed, where the ASSR was elicited by an amplitude
      modulated stimulus whose sound pressure level was slowly varied, or "swept," over
      a range of levels believed to bracket the threshold. The ASSR amplitude function
      was obtained by analyzing the resulting grand average evoked potential using a
      short-time Fourier transform. The suitability of this technique for hearing
      assessment of bottlenose dolphins and California sea lions was evaluated by
      comparing ASSR amplitude functions and thresholds obtained with swept amplitude
      and discrete, constant amplitude stimuli. When factors such as the number of
      simultaneous tones, the number of averages, and the frequency analysis window
      length were taken into account, the performance and time required for the swept
      amplitude and discrete stimulus techniques were similar. The decision to use one
      technique over another depends on the relative importance of obtaining
      suprathreshold information versus the lowest possible thresholds.

PMID- 21877817
TI  - Acoustically induced streaming flows near a model cod otolith and their potential
      implications for fish hearing.
AB  - The ears of fishes are remarkable sensors for the small acoustic disturbances
      associated with underwater sound. For example, each ear of the Atlantic cod
      (Gadus morhua) has three dense bony bodies (otoliths) surrounded by fluid and
      tissue, and detects sounds at frequencies from 30 to 500 Hz. Atlantic cod have
      also been shown to localize sounds. However, how their ears perform these
      functions is not fully understood. Steady streaming, or time-independent, flows
      near a 350% scale model Atlantic cod otolith immersed in a viscous fluid were
      studied to determine if these fluid flows contain acoustically relevant
      information that could be detected by the ear's sensory hair cells. The otolith
      was oscillated sinusoidally at various orientations at frequencies of 8-24 Hz,
      corresponding to an actual frequency range of 280-830 Hz. Phase-locked particle
      pathline visualizations of the resulting flows give velocity, vorticity, and rate
      of strain fields over a single plane of this mainly two-dimensional flow.
      Although the streaming flows contain acoustically relevant information, the
      displacements due to these flows are likely too small to explain Atlantic cod
      hearing abilities near threshold. The results, however, may suggest a possible
      mechanism for detection of ultrasound in some fish species.

PMID- 21877818
TI  - A numerical study on the propagation of Rayleigh and guided waves in cortical
      bone according to Mindlin's Form II gradient elastic theory.
AB  - Cortical bone is a multiscale heterogeneous natural material characterized by
      microstructural effects. Thus guided waves propagating in cortical bone undergo
      dispersion due to both material microstructure and bone geometry. However, above
      0.8 MHz, ultrasound propagates rather as a dispersive surface Rayleigh wave than
      a dispersive guided wave because at those frequencies, the corresponding
      wavelengths are smaller than the thickness of cortical bone. Classical
      elasticity, although it has been largely used for wave propagation modeling in
      bones, is not able to support dispersion in bulk and Rayleigh waves. This is
      possible with the use of Mindlin's Form-II gradient elastic theory, which
      introduces in its equation of motion intrinsic parameters that correlate
      microstructure with the macrostructure. In this work, the boundary element method
      in conjunction with the reassigned smoothed pseudo Wigner-Ville transform are
      employed for the numerical determination of time-frequency diagrams corresponding
      to the dispersion curves of Rayleigh and guided waves propagating in a cortical
      bone. A composite material model for the determination of the internal length
      scale parameters imposed by Mindlin's elastic theory is exploited. The obtained
      results demonstrate the dispersive nature of Rayleigh wave propagating along the
      complex structure of bone as well as how microstructure affects guided waves.

PMID- 21877871
TI  - Acute cardiac care. Editorial.

PMID- 21877870
TI  - Utilizing quantitative certificate of analysis data to assess the amount of
      excipient lot-to-lot variability sampled during drug product development.
AB  - Understanding variability in excipient physico-chemical properties is becoming an
      important aspect of Quality-by-Design drug product development. However, present
      experimental methods have only been able to study a few physico-chemical
      properties for a few excipient lots due to time, cost, and sample gathering
      considerations. An alternative analysis method is proposed here that shows how
      quantitative physico-chemical property data reported in vendor certificates of
      analysis can evaluate excipient lot-to-lot variability in a comprehensive and low
      cost manner. Microcrystalline cellulose, spray-dried lactose, and magnesium
      stearate were selected as commonly-used excipients for this demonstration. The
      proposed analysis method offers drug product developers several advantages over
      present experimental methods, including the ability to: (1) examine excipient
      products for manufacturing site and/or year-to-year variations, (2) quantify a
      domain of prior experience for each excipient by determining the percentage of
      excipient lots contained within a multi-dimensional ellipsoid described by the
      excipient lots used during drug product development, and (3) rationally select
      excipient lots from the vendors inventory to maximize the domain of prior
      experience throughout the drug development process. For cases where certificate
      of analysis data may contain insufficient information, drug product developers
      and excipient vendors should work together to identify more appropriate datasets
      for analysis.

PMID- 21877872
TI  - Impact of body mass index in the results after primary angioplasty in patients
      with ST segment elevation acute myocardial infarction.
AB  - INTRODUCTION: Obese patients submitted to elective coronary angioplasty have a
      paradoxical reduction in hospital and long-term mortality. In primary angioplasty
      setting, the relation with Body Mass Index (BMI) is less studied. OBJECTIVES: To
      evaluate the impact of obesity in the results after ST-segment elevation acute
      myocardial infarction treated by primary angioplasty. METHODS: Study of 539
      consecutive patients with ST-segment elevation acute myocardial infarction
      (STEMI) submitted to primary angioplasty. We evaluated in-hospital, 30-day and
      one-year all-cause mortality according to BMI: 'normal', <25 kg/m(2);
      'overweight', 25-29.9 kg/m(2) and 'obese', >= 30 kg/m(2). RESULTS: Obese patients
      were younger, had more hypertension and hyperlipidemia. There were no differences
      in previous cardiac history and hospital data. In-hospital mortality was 8.0% for
      patients with normal BMI, 4.4% for overweight patients and 5.9% for obese
      patients (P=0.296). At 30 days, 9.6%, 5.2% and 6.9% (P=0.212) and at first year,
      11.2%, 5.2% and 6.9% (P=0.064), respectively. Overweight was the only group with
      decreased risk (OR: 0.44, 95% CI: 0.21-0.90, P=0.015), even after adjustment for
      confounding variables (OR: 0.37, 95% CI: 0.15-0.95, P=0.038). CONCLUSIONS:
      Overweight patients had a better prognosis after primary angioplasty for STEMI
      compared with other BMI groups.

PMID- 21877873
TI  - Susceptibility genes for coronary heart disease and myocardial infarction.
AB  - Coronary heart disease and its main complication, myocardial infarction is
      leading cause of death worldwide. Over the past years, much progress has been
      made in the pharmacotherapy of major risk factors like dyslipidemias, diabetes
      mellitus and hypertension. The targeting of coronary risk factors coupled with
      advances in the management of coronary artery disease has improved patient
      survival. However, the incidence of cardiovascular disease is projected to
      continue to rise and the identification of individuals at risk should improve
      beyond the traditional models of global risk factor scoring. In the past few
      years, important progresses have been made in the area of genomics, especially
      with the completion of the human genome-sequencing Consortium of 2004, proteomics
      and imaging. This progress will promote a better understanding of cardiovascular
      risk assessments and disease prediction, thus allowing earlier preventive
      strategies to prevent and improve cardiovascular outcomes. These genomic advances
      have improved characterization of disease pathology especially at the molecular
      level with the discovery and introduction of genetic markers, single nucleotide
      polymorphisms (SNPs), and haplotype blocks.

PMID- 21877874
TI  - Impact of a territorial ST-segment elevation myocardial infarction network on
      prognosis of patients with out-of-hospital cardiac arrest.
AB  - INTRODUCTION: We sought to assess the effect of a territorial system of care for
      ST-elevation myocardial infarction (STEMI) on the outcome of out-of-hospital
      cardiac arrest (OOHCA). MATERIALS AND METHODS: We enrolled 720 patients who
      experienced a witnessed OOHCA of presumed cardiac origin during a four-year
      period in an area with a STEMI network and for whom resuscitation was attempted.
      RESULTS: Overall, 242 (33.6%) patients had return of spontaneous circulation
      (ROSC), 645 (90%) died before discharge. We observed a trend toward decreased
      overall mortality for OOHCA between the years 2004 and 2007, both in the entire
      population and in patients with ROSC (2004=94%; 2005=89%; 2006=85%; 2007=89%;
      P=0.064; 2004=81%; 2005=69%; 2006=65%; 2007=60%; P=0.076, respectively). On
      multivariable analysis, age, crew-witnessed arrest and presence of shockable
      rhythm were independent predictors of mortality. Patients who experienced OOHCA
      in the year 2006 (OR=0.47; 95% CI: 0.21-1.05; P=0.07) and 2007 (OR=0.51; 95% CI:
      0.23-1.12; P=0.09) showed a strong trend toward decreased risk of mortality
      compared to year 2004. In patients with ROSC, the year 2007 was associated with a
      significant lower risk of mortality compared to year 2004 (OR=0.38; 95% CI: 0.15
      0.96; P=0.04). CONCLUSIONS: Implementation of a territorial network of care for
      STEMI appears to be associated with reduced mortality OOHCA patients.

PMID- 21877875
TI  - Angiographic and long-term clinical outcome of the sleeve technique in treating
      in-stent restenotic bifurcation lesions: a preliminary experience.
AB  - BACKGROUND: No data has been published on the management of in-stent restenotic
      bifurcation lesions. The aim of this small case series was to examine the
      angiographic and long-term clinical outcomes of using sleeve technique to treat
      this lesion subset. METHODS: Six consecutive and symptomatic patients with MEDINA
      classification 1,1,1 in-stent restenotic bifurcation lesion were treated with
      drug-eluting stents using sleeve technique. Dual antiplatelet therapy was
      prescribed for an average of 13.5 +/- 2.3 months. RESULTS: Most of the lesions
      (87%) were located at LAD/diagonal branch bifurcation. Kissing balloon inflation
      was performed successfully in all the patients. Follow-up angiography at nine
      months revealed a late loss of 0.35 +/- 0.26 mm and 0.56 +/- 0.56 mm in MV and
      SB, respectively. Angiographic restenosis was developed in 2 patients (33%),
      which were all located at the SB ostium. No in-hospital MACE was observed. One
      year MACE was 17%, attributed by 1 patient with restenosis who needed
      revascularization. The mean follow up period was 50 +/- 18 months, no stent
      thrombosis was detected. CONCLUSIONS: The use of sleeve technique to treat in
      stent restenotic bifurcation lesions is associated with good acute procedural
      result, a fairly low one-year MACE and long-term clinical safety.

PMID- 21877876
TI  - Prevention of contrast-induced nephropathy with haemofiltration in high-risk
      patients after percutaneous coronary intervention.
AB  - BACKGROUND: The incidence of contrast-induced nephropathy (CIN) after
      percutaneous coronary intervention (PCI) is increasing. The aim of the study is
      to assess the benefits of prophylactic haemofiltration (PHF) in patients with
      high risk of developing CIN after PCI. METHODS: 20 patients who underwent PHF
      after PCI in the context of acute coronary syndrome were selected retrospectively
      and compared with 20 matched controls with similar risk characteristics. The main
      variable analysed was the appearance of CIN and the secondary variables were the
      development of acute clinical kidney failure, heart failure, therapeutic HF and
      mortality. RESULTS: The baseline characteristics were similar in both groups,
      with reference creatinine of 2.4 +/- 1.3 mg/dl, contrast used 392 +/- 213 cc and
      Mehran score of 21.9 +/- 5.2 in the PHF group, as opposed to values of 2.0 +/-
      0.6 mg/dl, 368 +/- 126 cc and 20.2 +/- 6.9 respectively in controls. The
      incidence of CIN was of 6 patients (30%) in the PHF group and 13 patients (65%)
      in the control group (P=0.03). There were no significant differences in the rest
      of the variables studied. CONCLUSION: Haemofiltration after PCI may be an
      effective strategy for the prevention of CIN in patients at high risk of
      developing it.

PMID- 21877877
TI  - Prognostic value of plasma B-type natriuretic peptide in patients with severe
      cardiotoxic drug poisoning.
AB  - BACKGROUND/OBJECTIVES: Cardiotoxic drug poisoning can lead to severe cardiac
      shock (CS) and death. B-type natriuretic peptide (BNP) is a well-established
      diagnostic and prognostic marker in heart failure but has never been assessed in
      patients with cardiotoxic drug poisoning. The aim of the study was to determine
      whether BNP could be useful for early stratification of patients admitted to
      intensive care unit. METHODS: 30 consecutive patients experiencing shock and
      cardiotoxic drug exposure were enrolled in a prospective monocentric study and
      underwent at least two BNP measurements within the first 24 h after admission.
      RESULTS: While BNP values on admission were poorly informative, subsequent BNP
      measurements (11 +/- 6 h after admission) were significantly increased in
      patients with CS compared to those with non-CS (756; [364-1130] versus 24; [15
      65] pg/ml respectively; P = 0.008). This second BNP level was also significantly
      increased in non-survivor patients compared to survivor patients (784; [654-1028]
      versus 29; [15-104] pg/ml respectively; P = 0.05): BNP levels above 360 pg/ml
      predicted in-hospital mortality (sensitivity = 100%, specificity = 92%). In a
      multivariate analysis, BNP, SAPS II score and lactate blood level were associated
      with death. CONCLUSIONS: Serial BNP measurements after admission for cardiotoxic
      drug poisoning are useful to identify patients at the highest risk of CS as well
      as in-hospital death.

PMID- 21877878
TI  - Right ventricular strain rate predicts clinical outcomes in patients with acute
      pulmonary embolism.
AB  - BACKGROUND: Echocardiographic quantification of global and regional right
      ventricular (RV) function is critical in patients with acute pulmonary embolism
      (PE), but remains a challenge particularly in acute RV dilatation. METHODS:
      Apical two-dimensional images of patients with acute PE were analyzed using both
      conventional and speckle tracking imaging compared with controls; patients with
      PE were divided into those who received thrombolysis and those who did not. The
      basal, mid and apical segments of the RV free wall and septum were analyzed.
      Correlations between speckle tracking measurements and in-hospital mortality were
      made. RESULTS: 53 patients with PE were compared with 15 controls. Of the PE
      patients, 98.1% were treated with systemic anticoagulation, 15.1% with
      thrombolysis; 38% required ICU admission and 5.6% died. Strain rate of the mid
      interventricular septum and strain of the basal and mid interventricular septal
      segments were significantly lower in patients with PE than control. However,
      strain rate of the basal RV free wall was higher than controls. In thrombolysed
      patients, basal RV free wall strain rate was lower than in non-thrombolysed
      patients. RV strain rate significantly correlated with in-hospital mortality.
      CONCLUSIONS: Speckle tracking may be a sensitive tool for assessing RV
      dysfunction and predicting mortality in patients with PE in this pilot study.

PMID- 21877879
TI  - Twiddler's syndrome.

PMID- 21877880
TI  - An unusual case of massive subcutaneous chest wall haemorrhage with enoxaparin.
AB  - Enoxaparin is used in the treatment of acute coronary syndromes and offers
      improved outcome in the composite endpoint of death, myocardial infarction and
      major bleeding when compared with unfractionated heparin (UFH). Our report
      describes a rare case of massive life-threatening subcutaneous chest wall
      haemorrhage, distant to the injection site. Clinicians should be aware of
      atypical presentations of haemorrhage when using combination antiplatelet and
      antithrombotic therapy.

PMID- 21877881
TI  - Good visibility of TITAN-2 coronary stents demonstrable on cardiac computer
      tomographic angiography: a report of 2 cases.
AB  - Numerous studies have sought to assess stent patency by cardiac computer
      tomographic angiography (CCTA) in comparison with invasive coronary angiography
      in patients who had undergone percutaneous coronary stenting. Even with newer
      generation scanners, CCTA has been of limited value in the assessment of the
      revascularized patient. The main reason being blooming artifact from metallic
      stents often obscures stent luminal dimension, making the stented segment
      unassessable. We report on a novel finding of good visibility of TITAN-2 coronary
      stents demonstrable on CCTA for 2 patients and discuss the possible mechanism and
      potential implications of this observation.

PMID- 21877882
TI  - Routine bone marrow biopsy is not necessary in the staging of patients with
      classical Hodgkin lymphoma in the 18F-fluoro-2-deoxyglucose positron emission
      tomography era.
AB  - Accurate staging of classical Hodgkin lymphoma (CHL) directs treatment intensity.
      Functional imaging can detect marrow/bone involvement making the role of bone
      marrow biopsy (BMB) unclear. We assessed current UK practice in CHL staging by
      questionnaire and retrospectively analyzed patients staged at a single center
      with BMB and (18)F-fluoro-2-deoxyglucose positron emission tomography/computed
      tomography (FDG-PET/CT). From 34 questionnaire responses 50% used FDG-PET/CT
      routinely. BMB was employed in 97% with advanced-stage and 30% of patients with
      limited-stage disease (70% of those not using routine FDG-PET/CT). Ten out of 50
      patients were BM+, all of which were identified by FDG-PET/CT (PET+).
      Conventional BMB changed management in 2% of cases. There were no clinically
      significant FDG-PET/CT false positives. Conventional routine BMB staging in CHL
      is extremely insensitive. FDG-PET/CT can rule out marrow/bone involvement in CHL.
      In the FDG-PET/CT staging era BMB should be targeted to a minority of patients
      with FDG-PET/CT + bone/marrow uptake and only when management would be altered by
      the result.

PMID- 21877884
TI  - EBF and dried blood spots: from recommendations to potential resolution.

PMID- 21877885
TI  - Are multiplex assays approvable?

PMID- 21877883
TI  - Outpatient consolidation treatment with clofarabine in a phase 2 study of older
      adult patients with previously untreated acute myelogenous leukemia.
AB  - This report describes outpatient (OP) administration of clofarabine in older
      patients (>=60 years) with untreated acute myelogenous leukemia (AML). Overall,
      112 patients underwent clofarabine induction. Clofarabine was administered to 35
      OPs for a total of 72 OP cycles, with 81% of these cycles representing
      consolidation treatment. Median length of hospital stay was 0-6 days and 5-25
      days across OP and inpatient (IP) cycles, respectively. The most common adverse
      events (AEs) were nausea, vomiting, diarrhea, febrile neutropenia, edema,
      hypokalemia and pneumonia. The overall frequency of treatment-emergent grade >=3
      AEs and serious AEs was generally not different with IP or OP administration of
      clofarabine. No deaths were reported within 30 days following OP or IP
      consolidation cycles. In the appropriately selected older patient, OP
      administration of clofarabine consolidation appears feasible, is as well
      tolerated as IP administration and has potential to contribute to the quality of
      life in elderly patients with AML.

PMID- 21877886
TI  - Accurate-mass instrumentation should not always be the first-and-only choice for
      MS in the drug metabolism environment.

PMID- 21877887
TI  - Understanding and mitigating impact of immunogenicity on pharmacokinetic assays.

PMID- 21877889
TI  - Bioanalysis-related highlights from the 2011 AAPS National Biotechnology
      Conference.
AB  - The American Association of Pharmaceutical Scientists is a dynamic international
      forum for the exchange of knowledge among scientists to enhance their
      contributions to drug development. The annual National Biotechnology Conference,
      conducted and organized by the American Association of Pharmaceutical Scientists,
      is a forum dedicated to advancements in science and technology related to
      discovery, development and manufacture of medical biotechnology products. The
      2011 National Biotechnology Conference meeting convened in San Francisco, CA, USA
      on 16-18 May. Over 300 abstracts were submitted and approximately 50 sessions
      examined topics pertaining to advances in drug development, emerging analytical
      technologies, bioanalysis-related issues, biosimilar therapies, updates on global
      regulatory documents and expectations, and other topics. The focus of this
      article is to highlight key developments relevant to immunogenicity and
      pharmacokinetic drug concentration bioanalysis.

PMID- 21877891
TI  - LC-MS/MS bioanalytical challenge: ultra-high sensitivity assays.
AB  - Anne-Francoise Aubry is Director of Bioanalytical Sciences at Bristol-Myers
      Squibb Co., leading a team in developing bioanalytical methods for early
      development drug candidates in support of toxicology and clinical studies. Her
      main research interests are high-speed, high-resolution LC and new approaches for
      LC-MS/MS drug bioanalysis in regulated laboratories. Anne Aubry is on the
      executive board of the Eastern Analytical Symposium and on the organizing
      committee of the Applied Pharmaceutical Analysis and Chemical and Pharmaceutical
      Structure Analysis (Shanghai 2011) conferences. The challenges of developing and
      running low pg/ml LC-MS/MS bioanalytical assays in a regulated laboratory are
      reviewed. The practical problems encountered in implementing ultrasensitive
      assays are less in reaching a suitable sensitivity on the instrument than in
      implementing procedures to control losses and contamination, eliminate matrix
      interferences and ensure assay robustness so that the assay can be validated to
      industry standards. Solutions to these problems can be found in each of the three
      facets of the bioanalytical assay: the sample preparation, the chromatographic
      separation and the mass spectrometric detection. The key to developing an
      ultrasensitive assay is to optimize each of these elements. Progress in MS
      instrumentation has been essential in our ability to reach the low pg/ml limits.

PMID- 21877892
TI  - Potentially new isobaric metabolite of fluvastatin observed by LC-MS/MS during
      incurred sample analysis.
AB  - BACKGROUND: Fluvastatin (Lescol((r))) is a racemic mixture of two erythro
      stereoisomers and metabolizes into two threo stereoisomers. A method was
      developed to chromatographically separate fluvastatin from its threo isomers to
      support a bioequivalence study. RESULTS: During incurred samples analysis, an
      additional peak sharing the same mass transition as fluvastatin was observed and
      interfered with fluvastatin's quantification. Consequently, the chromatographic
      conditions were modified in order to resolve fluvastatin and the interference.
      Extensive evaluations were performed to ensure that the interference is not a
      degradation product generated during sample processing. CONCLUSION: An isobaric
      compound of fluvastatin was discovered, which required chromatographic separation
      from fluvastatin to obtain a reliable bioanalytical method. The investigation
      performed suggests that the interference is produced in vivo and is a possible
      metabolite of fluvastatin.

PMID- 21877893
TI  - Analysis of total and transferrin-bound iron in human serum for pharmacokinetic
      studies of iron-sucrose formulations.
AB  - BACKGROUND: Patients with iron-deficiency anemia benefit from intravenous iron
      therapies. Development of these pharmaceutical agents requires pharmacokinetic
      studies monitoring levels of both the administered agent and transferrin-bound
      iron (TBI). Successful pharmacokinetic methods must discriminate iron species.
      RESULTS: Routine colorimetric procedures were used to reliably measure total iron
      and TBI following iron-sucrose administration. Iron was liberated from iron
      sucrose allowing the determination of all circulating iron. Solid-phase sample
      processing allowed the measurement of TBI. Circulating iron-sucrose could then be
      calculated as the difference between total iron and TBI. CONCLUSION: A
      reproducible and robust spectrophotometric method was developed and validated for
      measuring total iron and TBI in human serum following iron-sucrose therapy.

PMID- 21877894
TI  - Determination of tafenoquine in dried blood spots and plasma using LC and
      fluorescence detection.
AB  - BACKGROUND: The growing problem of parasites developing resistance to the
      traditional antimalarial drugs makes the development of new effective and safe
      drugs crucial. Tafenoquine is a new promising antimalarial drug for prophylaxis
      and treatment. RESULTS: A bioanalytical method for the determination of
      tafenoquine in 100 ul of capillary blood applied onto sampling paper and in 100
      ul of plasma has been developed and validated. The Whatman 31 ET Chr paper was
      treated with 0.6 mol/l tartaric acid to improve the extraction recovery and solid
      phase extraction was used for cleanup procedure of the blood samples. Plasma
      samples were precipitated with methanol. Tafenoquine and internal standard were
      separated on a Zorbax SB-CN column by reversed-phase LC and detected with
      fluorescence detection at 262 and 470 nm. The within- and between-day variations
      were below 10 and 14%, respectively, over the range 50-200 nmol/l for capillary
      blood on sampling paper and below 6 and 10% for plasma samples. The LLOQ of the
      method was 50 nmol/l. CONCLUSION: The developed method has adequate sensitivity
      and is highly suitable for clinical studies in dried blood spots and plasma.

PMID- 21877895
TI  - Validation of an LC-MS/MS assay for detecting relevant disaccharides from keratan
      sulfate as a biomarker for Morquio A syndrome.
AB  - BACKGROUND: Mucopolysaccharidosis IVA (MPS IVA, Morquio A syndrome) is an
      inherited lysosomal storage disease caused by deficiency of N-acetylgalactosamine
      6-sulfatase (GALNS), an enzyme required for stepwise degradation of keratan
      sulfate (KS). We have developed a selective, sensitive, accurate and precise LC
      MS/MS assay for the KS-derived disaccharides Galbeta1-4GlcNAc(6S) and
      Gal(6S)beta1-4GlcNAc(6S) in human urine and plasma using keratanase II digestion.
      RESULTS: Mean accuracy was 96-106% in urine and 97-108% in plasma. Precision was
      high, with relative standard deviations of 1-2% (intra-day) and 2-5% (inter-day)
      in urine and 1-2% (intra-day) and 4-7% (inter-day) in plasma. The lower limit of
      quantitation was 0.026 ug/ml (plasma) and 0.104 ug/ml (urine), with a
      quantitation range of 0.026-5 ug/ml (plasma) and 0.104-20 ug/ml (urine).
      CONCLUSION: Clinical sample analysis in 168 MPS IVA patients and 225 healthy
      controls demonstrates the clinical utility of this method.

PMID- 21877896
TI  - Case studies from the use of commercial biomarker/protein test kits.
AB  - Large-molecule drugs (therapeutic proteins, peptides, various forms of
      antibodies) are more frequently being seen in drug-development pipelines, the
      majority of which are measured using immunochemical/ligand-binding techniques.
      The assays utilized for analysis of large-molecule drugs rely heavily upon the
      quality of the components (e.g., reference materials, antibodies) that are
      critical to the performance of the assays. Commercially available research-grade
      materials and kits offer a convenient and simple solution, but also present some
      unique challenges. This article will explore some examples of issues encountered
      while employing commercially available kits and reagents.

PMID- 21877897
TI  - NMR spectroscopy for discovery and quantitation of biomarkers of disease in human
      bile.
AB  - Human liver synthesizes bile; bile, containing a large number of metabolites, is
      transported through the canaliculi and bile ducts, and stored in the gallbladder
      before entering into the intestine. In the intestine, a large number of bile
      metabolites are reabsorbed and sent back to the liver for recirculation. Owing to
      close association of the bile with the gastrointestinal system, the bile
      metabolic profile is highly sensitive to the onset of numerous gastrointestinal
      disease processes. A growing number of studies suggest that hepatobiliary disease
      biomarkers are richly populated in human bile. These studies stress the potential
      of profiling the human bile metabolome for early diagnostics as well as deeper
      insights into gastrointestinal disease processes. Once the biomarkers are
      established reliably using human bile, they can be targeted in easily accessible
      fluids such as blood and urine or targeted in bile itself using noninvasive
      methods such as in vivo magnetic resonance spectroscopy. NMR spectroscopy is one
      of the most powerful bioanalytical tools, which promises profiling of human bile
      metabolome and exploring early biomarkers for hepatobiliary diseases.
      Comprehensive analysis of human bile using NMR spectroscopy has lead to
      identification and quantification of major bile metabolites. This review
      describes the discovery and quantitation of biomarkers of hepatobiliary diseases
      in human bile using NMR spectroscopy.

PMID- 21877899
TI  - Update on cytogenetic and molecular changes in myelodysplastic syndromes.
AB  - Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis
      and a high propensity to transform to acute myeloid leukemia (AML). In the
      pathogenesis of the disease, both gene mutations and cytogenetic changes play an
      important role. The latter have been integrated into prognostic scoring systems
      including the IPSS (International Prognostic Scoring System) and WPSS (World
      Health Organization [WHO] classification-based Prognostic Scoring System). In
      these systems and in multivariate analyses comparing clinical and genetic data,
      complex karyotypes are associated with a particularly poor prognosis. del(5q)
      plays a distinct role by classifying the only genetically defined WHO subtype.
      Also, due to advancement in technology such as whole genome sequencing, the
      number of known mutations occurring in MDS is steadily increasing. Important
      recent discoveries include mutations in EZH2, DNMT3A, ASXL1 and IDH1/2. Like
      TET2, the most commonly mutated gene in MDS, all are involved in epigenetic
      regulation. Mutations such as ASXL1, RUNX1, EZH2, ETV6/TEL and TP53 have an
      adverse impact on patient overall survival. Early evidence suggests that some
      mutations might influence treatment response, necessitating reassessment of the
      prognostic effect of genetic alterations in the light of every new treatment.
      This review discusses clinical and biological effects of the most common
      cytogenetic and molecular aberrations in patients with MDS.

PMID- 21877900
TI  - An overview of systematic reviews of adaptive seating interventions for children
      with cerebral palsy: where do we go from here?
AB  - PURPOSE: This article provides an overview and assessment of systematic reviews
      of adaptive seating outcomes in children with cerebral palsy (CP) and proposes
      strategies to advance and improve the clinical utility of future research
      evidence. METHODS: A comprehensive search for systematic reviews was performed to
      locate and evaluate the functional effects of adaptive seating in children with
      CP. Relevant electronic databases were searched to identify reviews published
      between January 1990 and December 2010. RESULTS: The search yielded five reviews
      of adaptive seating interventions that found generally positive, but inconclusive
      evidence of effectiveness for postural control and management, seated posture,
      upper extremity function, and overall clinical outcomes. Review authors
      consistently reported that they were unable to combine data from original
      research studies to make sound clinical recommendations due to the low quality of
      studies, the lack of appropriate outcome indicators, and the heterogeneity and
      lack of clarity in population characteristics and adaptive seating interventions.
      CONCLUSIONS: Strategies to improve the quality and clinical relevance of new
      research evidence for adaptive seating interventions include the adoption of an
      expanded view of child functioning, a child motor function classification and
      development approach, and contemporary frameworks for the measurement and
      evaluation of assistive technology outcomes. [Box: see text].

PMID- 21877901
TI  - Pulmonary exposure of rats to ultrafine titanium dioxide enhances cardiac protein
      phosphorylation and substance P synthesis in nodose ganglia.
AB  - The inhalation of engineered nanoparticles stimulates the development of
      atherosclerosis and impairs vascular function. However, the cardiac effects of
      inhaled engineered nanoparticles are unknown. Here, we investigate the effects of
      ultrafine titanium dioxide (UFTiO(2)) on the heart, and we define the possible
      mechanisms underlying the measured effects. Pulmonary exposure of rats to
      UFTiO(2) increased the phosphorylation levels of p38 mitogen-activated protein
      kinase and cardiac troponin I, but not Akt, in the heart and substance P
      synthesis in nodose ganglia. Circulatory levels of pro-inflammatory cytokines,
      and blood cell counts and differentials were not significantly changed after
      pulmonary exposure. Separately, the incubation of cardiac myocytes isolated from
      naive adult rat hearts in vitro with UFTiO(2) did not alter the phosphorylation
      status of the same cardiac proteins. In conclusion, the inhalation of UFTiO(2)
      enhanced the phosphorylation levels of cardiac proteins. Such responses are
      likely independent of systemic inflammation, but may involve a lung-neuron
      regulated pathway.

PMID- 21877902
TI  - Extracellular protons reduce quantal content and prolong synaptic currents at the
      Drosophila larval neuromuscular junction.
AB  - Fluctuations in extracellular pH occur in the nervous system in response to a
      number of physiological and pathological processes, such as ischemia,
      hypercapnea, and high-frequency activity. Using the Drosophila larval
      neuromuscular junction, the author has examined acute effects of low and high pH
      on excitability and synaptic transmission. Acidification rapidly and reversibly
      reduces the size of electrically evoked excitatory junctional currents (EJCs) in
      a concentration-dependent manner, with transmission nearly abolished at pH 5.0.
      Conversely, raising pH to 7.8 increases EJC amplitude significantly. Further
      elevation to pH 8.5 causes an initial increase in amplitude, followed by
      profound, long-lasting depression of the synapse. Amplitudes of spontaneous
      miniature EJCs (mEJCs) are modestly, but significantly reduced at pH 5.0. It is
      therefore the number of quanta released per action potential, rather than the
      size of individual quanta, that is most strongly affected. Decay times of both
      EJCs and mEJCs are dramatically lengthened at low pH, suggesting that glutamate
      remains in the synaptic cleft for much longer than normal. Presynaptic
      excitability is also reduced, as indicated by increased latency between nerve
      shock and EJC onset. The response to low pH was not altered by mutations in genes
      encoding Transient Receptor Potential, Mucolipin subfamily (TRPML) and Slowpoke
      ion channels, which had previously been implicated as possible targets of
      extracellular protons. The author concludes that extracellular protons have
      strong effects on the release of glutamate and the time course of synaptic
      currents. These phenotypes can be exploited to study the mechanisms of acid
      mediated changes in neuronal function, and to pursue the way in which pH
      modulates synaptic function in normal and pathophysiological conditions.

PMID- 21877903
TI  - Group intervention for siblings of children with disabilities: a pilot study in a
      clinical setting.
AB  - PURPOSE: To study the effectiveness of a group intervention in a clinical setting
      designed to increase knowledge of disability and improve sibling relationship
      among siblings of children with disabilities. METHOD: A self-selected sample of
      54 younger and older siblings with typical development (ages 8-12 years) of
      children with attention deficit hyperactivity disorder (ADHD) (9), Asperger
      syndrome (7), autistic disorder (13), physical disability (8) and intellectual
      disability (17) participated in collateral sibling groups. The Sibling Knowledge
      Interview (SKI) and Sibling Relationship Questionnaire (SRQ) were administered
      pre- and post-intervention. RESULTS: SKI scores increased (p < 0.001) from pre-
      to post-intervention when merged diagnostic groups were compared. Comparisons of
      SRQ pre- and post-intervention scores across diagnostic sibling groups showed
      significantly different (p < 0.05) score patterns. CONCLUSIONS: The results were
      encouraging and contribute to further development of interventions meeting the
      needs of siblings of children with disabilities. In view of the limited empirical
      research on group interventions for siblings of children with disabilities future
      work is needed to investigate the effectiveness of such interventions. Particular
      attention should be given to siblings of children with autism and siblings of
      children with intellectual disability.

PMID- 21877906
TI  - Transmitted drug-resistant HIV type 1 remains prevalent and impacts virologic
      outcomes despite genotype-guided antiretroviral therapy.
AB  - Trends in transmitted drug resistance-associated mutations (TDRM) in HIV
      1infection vary depending on geographic and cohort characteristics. The impact of
      TDRM among patients receiving fully active combination antiretroviral therapy
      (cART) is poorly characterized. This was a retrospective study of 801 HIV-1
      infected treatment-naive patients from 2001 to 2009 who had pre-cART genotype
      resistance test results available. The prevalence of TDRM was compared for each
      year strata. Multivariate Cox proportional hazards regression models were used to
      assess factors associated with virologic failure at 48 weeks. TDRM was detected
      in 136 (17%) patients with >=2 class TDRM in 20 patients. K103N/S was the most
      frequent (n=77). There were no changes in the prevalence of mutations over time
      (P(trend)=0.67). Six hundred and eleven patients were started on cART. Virologic
      failure occurred in 38% of those with TDRM and 24% of those without (p<0.01). In
      multivariate analysis, nonnucleoside reverse transcriptase inhibitor (NNRTI)
      resistance was associated with a 1.5-fold increased risk of virologic failure.
      TDRM remains common among treatment-naive HIV-1-infected patients, affecting one
      in six patients. Transmission of NNRTI drug resistance was associated with risk
      of virologic failure despite initiation of genotype-guided cART.

PMID- 21877905
TI  - Thymosin beta 4 is associated with collateral development in coronary artery
      disease.
AB  - OBJECTIVES: Thymosin beta 4 (Tbeta4) plays an essential role in cardiac vessel
      development and is currently being developed as a therapeutic agent for the
      treatment of coronary artery disease (CAD) in some experimental studies. Thus, we
      aimed to investigate the association of serum Tbeta4 levels and collateral
      formation in patients presenting with severely stenotic CAD. METHODS: Thirteen
      patients with poor collateral development and 16 age- and sex-matched patients
      with good collateral development who had >= 95% stenosis in at least one major
      coronary artery on coronary angiogram (CAG) were enrolled in the study. The
      Gensini score was calculated for each patient by using CAG results. Collateral
      development was classified according to the Cohen-Rentrop method. Serum Tbeta4
      levels were measured with enzyme-linked immune sorbent assay. RESULTS: There were
      no statistically significant differences between the two groups in regard to
      clinical and laboratory characteristics of the patients except for Tbeta4 levels.
      The Tbeta4 levels in the well-collateralized study group were found to be
      significantly higher than those of the poorly collateralized study group and
      serum Tbeta4 levels were positively correlated with the collateral development.
      CONCLUSIONS: Our findings suggest that serum Tbeta4 levels are significantly
      associated with the collateral development in severe CAD.

PMID- 21877907
TI  - Disaster after the plaster. Fentanyl withdrawal symptoms in a curable hospice
      patient.
AB  - Opioids have been used for thousands of years for pain relief. Transdermal
      fentanyl (TDF) is a synthetic opioid that is prescribed for the treatment of
      chronic pain. This clinical lesson demonstrates that TDF may be easy to start but
      sometimes difficult to stop. Like any other opioid there is a substantial risk of
      physical dependence and subsequent withdrawal symptoms after discontinuation of
      the drug. Here, we present a case of a hospice patient who developed withdrawal
      symptoms after a first TDF tapering attempt according to the manufacturer's
      instructions. A second, more gradual tapering regimen did not result in
      withdrawal symptoms. The mechanisms and treatment modalities for physical
      dependence along with a tailor-made tapering strategy that is suitable for
      general practice are presented in this clinical lesson.

PMID- 21877904
TI  - The dysregulation of cytokine networks in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is an autoimmune disease associated with
      chronic immune activation and tissue damage. Organ damage in SLE results from the
      deposition of immune complexes and the infiltration of activated T cells into
      susceptible organs. Cytokines are intimately involved in every step of the SLE
      pathogenesis. Defective immune regulation and uncontrolled lymphocyte activation,
      as well as increased antigen presenting cell maturation are all influenced by
      cytokines. Moreover, expansion of local immune responses as well as tissue
      infiltration by pathogenic cells is instigated by cytokines. In this review, we
      describe the main cytokine abnormalities reported in SLE and discuss the
      mechanisms that drive their aberrant production as well as the pathogenic
      pathways that their presence promotes.

PMID- 21877908
TI  - Mesenchymal stem cells as therapeutic delivery vehicles targeting tumor stroma.
AB  - The field of stem cell biology continues to evolve by characterization of further
      types of stem cells and by exploring their therapeutic potential for experimental
      and clinical applications. Human mesenchymal stem cells (hMSCs) are one of the
      most promising candidates simply because of their easiness of both ex vivo
      expansion in culture dishes and genetic manipulation. Despite many extensive
      isolation and expansion studies, relatively little has been done with regard to
      hMSCs' therapeutic potential. Although clinical trials using hMSCs are underway,
      their use in cancer therapy still needs better understanding and in vivo
      supporting data. The homing ability of hMSCs was investigated by creating a human
      xenograft model by transplanting an ovarian cancer cell line into
      immunocompromised mice. Then, genetically engineered hMSC-telo1 cells were
      injected through the tail vein and the contribution and distribution of hMSCs to
      the tumor stroma were investigated by immunohistochemistry and PCR specific to
      the telomerase gene. Results show that exogenously administered hMSCs
      preferentially home, engraft, and proliferate at tumor sites and contribute to
      the population of stromal fibroblasts. In conclusion, this study provides support
      for the capacity of hMSCs to home to tumor site and serve as a delivery platform
      for chemotherapeutic agents.

PMID- 21877909
TI  - Targeted nuclear imaging of breast cancer: status of radiotracer development and
      clinical applications.
AB  - Breast cancer is the most common cancer in women worldwide. Molecular imaging
      plays an important role in breast cancer diagnosis, staging, and treatment
      response evaluation. Positron emission tomography (PET) and single-photon
      emission computed tomography (SPECT) are the main clinical molecular imaging
      modalities that are based on the detection of radiotracers. This article
      discusses the typical radiotracers used for breast cancer imaging by PET and
      SPECT. In addition, radiotracers that are currently applied for human breast
      cancer imaging or under clinical trials are also reviewed in compliance with the
      categories of tumor-specific targets to which they are aimed at.

PMID- 21877910
TI  - Classification and detection of errors in minimally invasive surgery.
AB  - PURPOSE: To provide a comprehensive review of the classification of surgical
      errors as well as general measures to detect and prevent their occurrence.
      MATERIALS AND METHODS: Search in PubMed, Medline, and Cochrane library with
      combination of the key words: Endoscopy or surgical procedures, minimally
      invasive, and medical error. Relevant articles were selected by three senior
      authors involved in minimally invasive surgery (MIS). RESULTS: Error is an
      unintended healthcare outcome caused by a defect in the delivery of care to a
      patient. Surgical errors are common and account for half of all hospital adverse
      events (AEs). Urology is the fifth specialty in decreasing order of AE. Errors
      may be classified according to the place where they occur (co-face or systemic),
      to the outcomes (near miss, recovery, and remediation). A specific classification
      for errors in MIS has also been described (Cushieri), depending on the step of
      the surgical procedure in which they occur. Each classification serves definite
      purposes, and no one can be definitive over the others. No classification has
      been applied so far to urology. Detection through appropriate reporting is the
      basis for prevention. CONCLUSION: Surgical errors represent a significant
      proportion of all medical error. Multiple classifications exist, depending on the
      purposes they are intended to serve. A classification based on the place of
      occurrence of the errors has been adopted in the medical system; however, when
      referring to MIS, a finer classification is proposed.

PMID- 21877911
TI  - Supine versus prone position during percutaneous nephrolithotomy: a report from
      the clinical research office of the endourological society percutaneous
      nephrolithotomy global study.
AB  - PURPOSE: To determine differences in patients' characteristics, operative time
      and procedures, and perioperative outcomes between prone and supine positioning
      in percutaneous nephrolithotomy (PCNL) using the Clinical Research Office of the
      Endourological Society (CROES) PCNL Global Study database. PATIENTS AND METHODS:
      Between November 2007 and December 2009, prospective data were collected on a
      total of 5803 consecutive patients who were treated over a 1-year period at each
      of 96 participating global centers. Patients with data on body position were
      dichotomized into prone or supine PCNL. RESULTS: The majority of PCNL treatments
      were performed in the prone position (n=4637; 80.3% of sample). Differences in
      patient characteristics included in the prone group: A greater proportion of
      males (57.4% vs 52.2%); younger age (48.8 y vs 51.0 y); less frequent history of
      shockwave lithotripsy (19.5% vs 28.6%); greater frequency of American Society of
      Anesthesiologists score of 1 (54.7% vs 46.8%); and a Clavien grade of 2 or more
      (10.0% vs 7.2%). The mean operative time was significantly lower for prone vs
      supine PCNL (82.7 min vs 90.1 min) regardless of the method of tract dilation,
      while the stone-free rate was significantly higher (77.0% vs 70.2%). Compared
      with supine patients, prone patients exhibited higher rates of blood transfusions
      (6.1% vs 4.3%) and fever (11.1% vs 7.6%), but lower rates of failed procedures
      (1.5% vs 2.7%). CONCLUSIONS: Since operative time and stone-free rates favor
      prone PCNL, but patient safety favors supine PCNL, the choice of patient position
      should be tailored to individual patient characteristics and the surgeon's
      preference.

PMID- 21877912
TI  - Current minimally invasive practice patterns among postgraduate urologists.
AB  - PURPOSE: To determine laparoscopic and robotic surgical practice patterns among
      current postgraduate urologists. MATERIALS AND METHODS: There were 9,095
      electronic surveys sent to practicing urologists with e-mail addresses registered
      with the American Urological Association. RESULTS: Responses were received from
      864 (9.5%) urologists; 84% report that laparoscopic or robotic procedures are
      performed in their practice. The highest training obtained by the primary
      laparoscopist was fellowship (31%), residency (23%), or 2- to 3-day courses
      (22%). Eighty-six percent report performance of laparoscopic nephrectomy in their
      practice, and 71% consider it the standard of care. Sixty-six percent of
      practices have access to at least one robotic unit, and 9% plan on purchasing one
      within a year. Attitudes toward robotics are favorable, with 80% indicating that
      it will increase in volume and potential procedures. Thirty-one percent state
      that robot-assisted prostatectomy is standard of care, while 50% believe this
      procedure looks promising. Respondents think that optimal training in minimally
      invasive techniques is fellowships (23%), minifellowships (23%), or hands-on
      courses (23%). Twenty-nine percent think that they were trained adequately in
      laparoscopy and robotics from residency, and 62% believe residents should be able
      to perform most laparoscopic procedures on completion of residency. CONCLUSIONS:
      The practice and availability of laparoscopic and robotic procedures have
      increased since previous evaluations. Opinions regarding these techniques are
      favorable and optimistic. As the field of urology continues to see a growing
      demand for minimally invasive procedures, training of postgraduate urologists and
      residents remains essential.

PMID- 21877914
TI  - Volcano-ice interaction as a microbial habitat on Earth and Mars.
AB  - Volcano-ice interaction has been a widespread geological process on Earth that
      continues to occur to the present day. The interaction between volcanic activity
      and ice can generate substantial quantities of liquid water, together with steep
      thermal and geochemical gradients typical of hydrothermal systems. Environments
      available for microbial colonization within glaciovolcanic systems are wide
      ranging and include the basaltic lava edifice, subglacial caldera meltwater
      lakes, glacier caves, and subsurface hydrothermal systems. There is widespread
      evidence of putative volcano-ice interaction on Mars throughout its history and
      at a range of latitudes. Therefore, it is possible that life on Mars may have
      exploited these habitats, much in the same way as has been observed on Earth. The
      sedimentary and mineralogical deposits resulting from volcano-ice interaction
      have the potential to preserve evidence of any indigenous microbial populations.
      These include jokulhlaup (subglacial outflow) sedimentary deposits, hydrothermal
      mineral deposits, basaltic lava flows, and subglacial lacustrine deposits. Here,
      we briefly review the evidence for volcano-ice interactions on Mars and discuss
      the geomicrobiology of volcano-ice habitats on Earth. In addition, we explore the
      potential for the detection of these environments on Mars and any biosignatures
      these deposits may contain.

PMID- 21877913
TI  - Noninferiority effects on glycemic control and beta-cell function improvement in
      newly diagnosed type 2 diabetes patients: basal insulin monotherapy versus
      continuous subcutaneous insulin infusion treatment.
AB  - AIMS: In newly diagnosed type 2 diabetes mellitus (T2DM) patients, short-term
      insulin therapy might improve beta-cell function and glycemic control. This study
      aimed to compare the effects of basal insulin monotherapy with continuous
      subcutaneous insulin infusion (CSII) treatment. METHODS: Fifty-nine cases of
      newly diagnosed T2DM patients with fasting plasma glucose of 9.0-16.7 mmol/L were
      recruited into this study. They were hospitalized and randomly assigned to a
      basal insulin monotherapy group (n=27) or a CSII group (n=32). Insulin dosage was
      titrated according to fasting capillary blood glucose levels, and treatment was
      stopped after 2 weeks. Intravenous glucose tolerance tests were performed, and
      blood glucose, insulin, C-peptide, and lipid profiles were measured before
      therapy and 2 days after therapy withdrawal. RESULTS: Both treatments reduced
      fasting and postprandial blood glucose levels (after treatment vs. baseline, both
      P<0.05). Fasting glycemic control target was achieved in 52 cases (88.14%) with 2
      weeks of insulin treatment, and there were no significant differences between the
      glargine and CSII groups (P=0.059). The time to achieve fasting glycemic target
      in the CSII group was shorter than that in the glargine group (P<0.01). Plasma
      lipid profiles such as triglycerides and total cholesterol also decreased
      significantly after the intervention. Overall beta-cell function improved
      significantly after insulin intervention (P<0.01). Variation did not differ
      between two groups, nor did the effects on insulin and C-peptide secretion
      (P>0.05). CONCLUSIONS: The effect of basal insulin monotherapy was similar to
      that of CSII, and thus basal insulin monotherapy might be a reasonable
      alternative to CSII for initial insulin therapy in newly diagnosed T2DM patients.

PMID- 21877916
TI  - Cesarean section and postpartum depression in a cohort of Chinese women with a
      high cesarean delivery rate.
AB  - BACKGROUND: Whether or not cesarean delivery is associated with increased risk of
      postpartum depression (PPD) remains unclear. METHODS: We carried out a
      prospective cohort study between February and September 2007 in Hunan Maternal
      and Infant Hospital and the First Affiliated and Third Affiliated Hospitals of
      the Central South University in Changsha, Hunan, People's Republic of China. The
      Chinese version of the Edinburgh Postnatal Depression Scale (EPDS) was used at 2
      weeks postpartum to assess PPD, with a score of >=13 as the cutoff for PPD.
      RESULTS: A total of 534 women were included in the final analysis, with 415
      (77.7%) delivering by cesarean section (the majority of them with no medical
      indication). The rate of PPD was 21.7% in women who had a cesarean delivery and
      10.9% in women who delivered vaginally. The increased risk of PPD in women who
      had cesarean sections was maintained after we adjusted for potential confounding
      factors or considered cesarean delivery by social indications. CONCLUSIONS:
      Cesarean section is associated with increased risk of PPD in Chinese women with a
      high cesarean delivery rate.

PMID- 21877917
TI  - Manipulation of oxygenation and flow-induced shear stress can increase the in
      vitro yield of platelets from cord blood.
AB  - A method to produce clinically useful platelets in vitro would help overcome the
      frequent shortages, donor deferrals, disease transmission, and alloimmunization
      with volunteer donor-derived platelets. Using CD34 positively selected cord blood
      cells, we investigated ways to increase platelet quality and yield in a three
      dimensional modular perfusion bioreactor system. We found a two- to threefold
      increase in platelet numbers produced only when the early phases of the culture
      process were carried out at 5% oxygen, versus when 20% oxygen was used throughout
      the culture period (p<0.05), and much more than when 5% oxygen was used
      throughout. When the medium was routed through the cell-scaffold construct,
      versus when it flowed under and over the construct, or just intermittent feeding
      was used, the number of platelets increased two- to threefold (p<0.05), and
      enhanced collagen-induced aggregation. The 5% oxygen early in the culture process
      mimics the marrow adjacent to the bone where early progenitors proliferate. Flow
      through the cell-scaffold construct creates shear forces that mimic the flow in
      central venous sinuses of the marrow and enhances platelet production from
      proplatelets. The use of altered oxygen levels and cross flow enhanced platelet
      numbers and quality, and will contribute to eventual in vitro platelet production
      for clinical use.

PMID- 21877915
TI  - Maternal depression in the United States: nationally representative rates and
      risks.
AB  - OBJECTIVES: To examine the public health burden of major depressive disorder
      (MDD) among mothers: its prevalence and sociodemographic patterns; associated
      functioning, comorbidities, and adversities; and racial/ethnic disparities.
      METHODS: This was a cross-sectional analysis of 8916 mothers in the National
      Epidemiologic Survey of Alcohol and Related Conditions, a nationally
      representative survey of the civilian U.S. population in 2001?2002. Past-year MDD
      was assessed with a structured interview protocol. RESULTS: Ten percent of
      mothers experienced depression in the past year. White and Native American women,
      those with low education or income, and those not married had high rates of
      depression. Depression was not strongly patterned by number of or age of
      children. Depressed mothers experienced more adversities (poverty, separation or
      divorce, unemployment, financial difficulties) and had worse functioning. Half of
      depressed mothers received services for their depression. Black and Hispanic
      depressed mothers were more likely to experience multiple adversities and less
      likely to receive services than white depressed mothers. CONCLUSIONS: Maternal
      depression is a major public health problem in the United States, with an
      estimated 1 in 10 children experiencing a depressed mother in any given year.
      Professionals who work with mothers and children should be aware of its
      prevalence and its detrimental effects.

PMID- 21877918
TI  - The response of type 2 quorum sensing in Klebsiella pneumoniae to a fluctuating
      culture environment.
AB  - Bacterial cells communicate with one another using chemical signaling molecules.
      This phenomenon is termed quorum sensing (QS). QS in Klebsiella pneumoniae is
      mediated by the synthesis of interspecies autoinducer 2 (AI-2), a furanosyl
      borate diester molecule. The response of Type 2 QS to environmental cues such as
      carbon sources, the initial pH of the medium, and boracic acid was investigated
      in the present study using a Vibrio harveyi BB170 reporter assay and quantitative
      reverse transcription-polymerase chain reaction (qRT-PCR) analysis. The results
      show that glucose can affect AI-2 synthesis to the greatest extent, and 3.0%
      glucose can stimulate K. pneumoniae to produce more AI-2, with a four times
      increase in activity compared with that of the control culture. According to our
      previous research, Type 2 QS in K. pneumoniae is luxS dependent. Therefore, the
      close relationship between glucose concentration and luxS transcription level was
      confirmed with qRT-PCR technology. The results show that the response of QS to a
      fluctuating glucose concentration was observed as a change in the amount of luxS
      RNA transcripts. A maximum of luxS transcription appeared during the exponential
      growth phase when the glucose concentration was 30.0 g/L. At the same time, AI-2
      production was also slightly impacted by the low initial pH. It is noteworthy
      that the addition of boracic acid at microdosage (0.1 g/L) can also induce AI-2
      synthesis. Presumably, in K. pneumoniae, the 4,5-dihydroxy-2,3-pentanedione
      cyclizes by the addition of borate and loss of water, is hydrated, and is
      converted to the final AI-2 signaling molecule.

PMID- 21877919
TI  - Recurrent G41S mutation in Cu/Zn superoxide dismutase gene (SOD1) causing
      familial amyotrophic lateral sclerosis in a large Polish family.
AB  - Mutations in the superoxide dismutase-1 (SOD1) gene have been found in 12-23% of
      patients with a diagnosis of ALS. Here we describe a large ALS Polish family with
      a branch in France, carrying a G41S mutation in the SOD1, and characterized by an
      early onset of the disease and extremely short survival time. The mutation has
      been initially detected in Italian ALS families with common founder effect.
      However, in the Polish population the G41S mutation most probably originated from
      an independent mutation event, as indicated by haplotype analysis. Collected data
      support the hypothesis that a SOD1 mutation is not the sole factor determining
      the clinical ALS phenotype.

PMID- 21877921
TI  - Thyroid targeted Kras(G12D)/Pten(-/-) mice and their cell lines: new tools to
      study thyroid cancer biology.

PMID- 21877923
TI  - Electronic health record use to classify patients with newly diagnosed versus
      preexisting type 2 diabetes: infrastructure for comparative effectiveness
      research and population health management.
AB  - Use of electronic health record (EHR) content for comparative effectiveness
      research (CER) and population health management requires significant data
      configuration. A retrospective cohort study was conducted using patients with
      diabetes followed longitudinally (N=36,353) in the EHR deployed at outpatient
      practice networks of 2 health care systems. A data extraction and classification
      algorithm targeting identification of patients with a new diagnosis of type 2
      diabetes mellitus (T2DM) was applied, with the main criterion being a minimum 30
      day window between the first visit documented in the EHR and the entry of T2DM on
      the EHR problem list. Chart reviews (N=144) validated the performance of refining
      this EHR classification algorithm with external administrative data. Extraction
      using EHR data alone designated 3205 patients as newly diagnosed with T2DM with
      classification accuracy of 70.1%. Use of external administrative data on that
      preselected population improved classification accuracy of cases identified as
      new T2DM diagnosis (positive predictive value was 91.9% with that step).
      Laboratory and medication data did not help case classification. The final cohort
      using this 2-stage classification process comprised 1972 patients with a new
      diagnosis of T2DM. Data use from current EHR systems for CER and disease
      management mandates substantial tailoring. Quality between EHR clinical data
      generated in daily care and that required for population health research varies.
      As evidenced by this process for classification of newly diagnosed T2DM cases,
      validation of EHR data with external sources can be a valuable step.

PMID- 21877920
TI  - Efficient generation of A9 midbrain dopaminergic neurons by lentiviral delivery
      of LMX1A in human embryonic stem cells and induced pluripotent stem cells.
AB  - Human embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC) offer
      great hope for in vitro modeling of Parkinson's disease (PD), as well as for
      designing cell-replacement therapies. To realize these opportunities, there is an
      urgent need to develop efficient protocols for the directed differentiation of
      hESC/iPSC into dopamine (DA) neurons with the specific characteristics of the
      cell population lost to PD, i.e., A9-subtype ventral midbrain DA neurons. Here we
      use lentiviral vectors to drive the expression of LMX1A, which encodes a
      transcription factor critical for ventral midbrain identity, specifically in
      neural progenitor cells. We show that clonal lines of hESC engineered to contain
      one or two copies of this lentiviral vector retain long-term self-renewing
      ability and pluripotent differentiation capacity. Greater than 60% of all neurons
      generated from LMX1A-engineered hESC were ventral midbrain DA neurons of the A9
      subtype, compared with ~10% in green fluorescent protein-engineered controls, as
      judged by specific marker expression and functional analyses. Moreover, DA neuron
      precursors differentiated from LMX1A-engineered hESC were able to survive and
      differentiate when grafted into the brain of adult mice. Finally, we provide
      evidence that LMX1A overexpression similarly increases the yield of DA neuron
      differentiation from human iPSC. Taken together, our data show that stable
      genetic engineering of hESC/iPSC with lentiviral vectors driving controlled
      expression of LMX1A is an efficient way to generate enriched populations of human
      A9-subtype ventral midbrain DA neurons, which should prove useful for modeling PD
      and may be helpful for designing future cell-replacement strategies.

PMID- 21877924
TI  - Liraglutide narrows the range of circadian glycemic variations in Japanese type 2
      diabetes patients and nearly flattens these variations in drug-naive type 2
      diabetes patients: a continuous glucose monitoring-based study.
AB  - BACKGROUND: Liraglutide was examined for its effects on 24-h glucose fluctuations
      in Japanese type 2 diabetes patients as well as for its differential effects
      depending on glucose tolerance status after favorable glycemic control was
      obtained in these patients. PATIENTS AND METHODS: In this prospective open-label
      pilot study, a total of 20 type 2 diabetes patients hospitalized for glycemic
      control were given liraglutide 0.3 mg, followed by liraglutide 0.6 mg and 0.9 mg,
      with each given at 1-week intervals. The patients were continuously monitored for
      their 24-h glucose levels before treatment and during the course of treatment
      with liraglutide 0.3 mg, 0.6 mg, and 0.9 mg, respectively, using continuous
      glucose monitoring (CGM). At the start of treatment with liraglutide, 12 patients
      were on diet therapy alone, of which six were drug-naive, and eight were being
      treated with glimepiride. RESULTS: Liraglutide not only significantly reduced 24
      h mean glucose levels but also significantly improved all the indices for
      glycemic variation evaluated, which included SDs of 24-h glucose levels, mean
      amplitude of glycemic excursions (MAGE), and total area under the glucose
      fluctuation curve (AUC) for 24 h. The study showed a significant negative
      correlation for mean glucose levels, SD, and AUC immediately before treatment
      versus their changes with liraglutide. A 75-g oral glucose tolerance test (OGTT)
      was given in 11 patients treated with liraglutide monotherapy once favorable
      glycemic control was achieved. The OGTT revealed that of these, six were found to
      have normal glucose tolerance, four had impaired glucose tolerance, and one had
      diabetes, and that of the six drug-naive patients, five patients were found to
      have normal glucose tolerance, and one had impaired glucose tolerance.
      CONCLUSIONS: Study results showed that liraglutide is expected not only to reduce
      mean glucose levels but also to improve 24-h glucose fluctuations, including
      postprandial glucose excursions, with its effects being particularly conspicuous
      in patients with early-stage type 2 diabetes.

PMID- 21877925
TI  - Effect of palliative care services on the aggressiveness of end-of-life care in
      the Veteran's Affairs cancer population.
AB  - BACKGROUND: Cancer care near the end of life (EOL) has become more aggressive
      over the years. Palliative care services (PCS) may decrease this aggressive
      cancer care in terminally ill cancer patients. Our objective was to observe the
      aggressiveness of cancer care near the EOL among Veterans Affairs cancer patients
      before and after the institution of a PCS team. We also assessed the time taken
      prior to death to initiate a PCS consultation and its effect on the
      aggressiveness of cancer care near the EOL. METHODS: This is a retrospective
      chart review analysis performed at the local Veterans Affairs hospital looking at
      the last 100 patients in each of the years, 2002 and 2008, who died with active
      cancer. Only patients in 2008 had access to a PCS team. RESULTS: In the last 30
      days of life, compared to 2002, patients in 2008 had a higher incidence of:
      chemotherapy administration, more than one hospital admission, more than 14 days
      of hospital stay, intensive care unit admissions, and in-hospital deaths.
      Patients with timely PCS consults in 2008 appeared to have a lower incidence of:
      chemotherapy administration, more than one emergency department visit, more than
      one hospital admission, more than 14-day hospital stays, intensive care unit
      admissions, and deaths in the hospital. Timely PCS consults were associated with
      earlier and more frequent hospice referral. CONCLUSIONS: Cancer care near the EOL
      has become more aggressive with time at one of the hospitals in the Veterans
      Affairs healthcare system (VAHS). Institution of a PCS service was unable to
      completely decrease this trend of increasing aggressiveness of cancer care near
      the EOL. However, timely PCS consults may help attenuate this aggressiveness.

PMID- 21877926
TI  - Impact of HIV type 1 DNA levels on spontaneous disease progression: a meta
      analysis.
AB  - Several studies have reported the prognostic strength of HIV-1 DNA with variable
      results however. The aims of the current study were to estimate more accurately
      the ability of HIV-1 DNA to predict progression of HIV-1 disease toward acquired
      immunodeficiency syndrome (AIDS) or death, and to compare the prognostic
      information obtained by HIV-1 DNA with that derived from plasma HIV-1 RNA.
      Eligible articles were identified through a comprehensive search of Medline, ISI
      Web of Science, Scopus, and Google Scholar. The analysis included univariate and
      bivariate random-effects models. The univariate meta-analysis of six studies
      involving 1074 participants showed that HIV-1 DNA was a strong predictive marker
      of AIDS [relative risk (RR): 3.01, 95% confidence interval (CI): 1.88-4.82] and
      of all-cause mortality (RR: 3.49, 95% CI: 2.06-5.89). The bivariate model using
      the crude estimates of primary studies indicated that HIV-1 DNA was a
      significantly better predictor than HIV-1 RNA of either AIDS alone (ratio of
      RRs=1.47, 95% CI: 1.05-2.07) or of combined (AIDS or death) progression outcomes
      (ratio of RRs=1.51, 95% CI: 1.11-2.05). HIV-1 DNA is a strong predictor of HIV-1
      disease progression. Moreover, there is some evidence that HIV-1 DNA might have
      better predictive value than plasma HIV-1 RNA.

PMID- 21877927
TI  - Influence of physical activity on metabolic state within a 3-h interruption of
      continuous subcutaneous insulin infusion in patients with type 1 diabetes.
AB  - BACKGROUND: The aim of this study was to evaluate the influence of physical
      activity on blood glucose, insulinemia, and ketone bodies level during
      interruption of insulin delivery. METHODS: We enrolled 12 patients with type 1
      diabetes (men with an average age of 33.4+/-8.66 years, body mass index of 25.7+/
      3.75 mg/m(2), and glycated hemoglobin of 8.4+/-0.95%). The test was performed
      after overnight fasting at the usual insulin dosage. The delivery of insulin by
      the pump was stopped for 3 h, and blood samples were obtained in 30-min intervals
      for determination of blood glucose, insulinemia, beta-hydroxybutyrate, non
      esterified fatty acids, and acid-base balance parameters. A test with (EXE) or
      without (CON) physical exercise (moderate aerobic exercise) was performed in each
      patient at random in the course of 2 weeks. Results are presented as median
      (first quartile; third quartile). RESULTS: Groups CON and EXE did not differ in
      blood levels of insulin during the test. Regarding time course of glycemia, we
      found differences only in min 270 for CON versus EXE of 15.2 (13.6; 16.7) and
      13.9 (9.1;16.5) mmol/L, respectively (P=0.038). Concerning blood levels of beta
      hydroxybutyrate, we found significant differences in min 180-300 of the test: CON
      of 419 (354; 541), 485 (344; 580), and 107 (63; 156) MUmol/L versus EXE of 690
      (631; 723), 703 (562; 871), and 241 (113; 507) MUmol/L (P<0.01). Comparable
      results were found in values of total ketone bodies and free fatty acids.
      CONCLUSIONS: The influence of physical activity during a 3-h interruption of
      insulin pump treatment is evident, especially in the increase in plasma levels of
      non-esterified fatty acids and ketone bodies. Correction bolus leads to a rapid
      increase in insulinemia; however, normalization of blood glucose and ketone
      bodies is achieved within another 90 min.

PMID- 21877928
TI  - Clostridium difficile in poultry and poultry meat.
AB  - The incidence and severity of disease associated with toxigenic Clostridium
      difficile have increased in hospitals in North America from the emergence of
      newer, more virulent strains. Toxigenic C. difficile has been isolated from food
      animals and retail meat with potential implications of transfer to human beings.
      The objective of the present study was to determine the prevalence of toxigenic
      C. difficile in chickens and retail poultry meat in Texas. Seven C. difficile
      isolates were detected in fecal samples of 300 (2.3%) broiler chickens. Three
      cultivation procedures were evaluated for isolation of C. difficile from poultry
      meat and detected 1/32 (3.1%), 2/32 (6.2%), and 4/32 (12.5%) for the three
      procedures, respectively. Chicken and poultry meat isolates were characterized as
      toxinotype V and pulsed-field gel electrophoresis gel type-NAP7 or NAP7-variant.
      Susceptibilities to 11 antimicrobial agents in the current study suggested
      somewhat reduced resistance than reported for other meat or animal toxinotype V
      isolates.

PMID- 21877929
TI  - Prevalence and mechanisms of quinolone resistance among selected nontyphoid
      Salmonella isolated from food animals and humans in Korea.
AB  - The aim of this study was to investigate the prevalence and mechanism of
      quinolone resistance among selected nontyphoid Salmonella (NTS) isolates. A total
      of 1279 NTS isolated from food animals (n=692) and humans (n=587) between 1995
      and 2009 were investigated by serotyping, antimicrobial susceptibility testing,
      screening for plasmid-mediated quinolone resistance (PMQR) genes qnr, aac(6')-Ib
      cr, and qepA and mutations in the quinolone resistance-determining region (QRDR)
      of gyrA and parC by PCR, and DNA sequencing. Three hundred thirty (47.7%) of 692
      animal isolates and 177 (30.2%) of 587 human isolates were resistant to nalidixic
      acid. Most animal (94.8%, 313/330) and human (99.4%, 176/177) NTS exhibited
      decreased ciprofloxacin susceptibility (minimum inhibitory concentration [MIC]:
      0.125-2 mg/L). None of them carried qnr or qepA gene. However, aac(6')-Ib was
      identified in six animal isolates, of which four carried aac(6')-Ib-cr gene.
      Based on antimicrobial resistance profile, year of isolation, MIC for quinolones
      and fluoroquinolones, and isolation frequency of serotype, 114 animal and 83
      human isolates were tested for QRDR mutations. All contained a single mutation
      within the QRDR of gyrA at either codon 87 or 83, and 41 of them contained an
      additional mutation in parC. The most prevalent mutation was Asp87-Tyr (n=107),
      followed by Asp87-Gly (n=28), Asp87-Asn (n=26), Ser83-Tyr (n=22), and Ser83-Phe
      (n=14). Point mutations in parC were observed outside the QRDR, which included 40
      isolates with Thr57-Ser substitution and 1 Salmonella Typhimurium with a novel
      Glu51-Lys substitution. In conclusion, a point mutation within the QRDR of gyrA
      was primarily responsible for quinolone resistance and reduced susceptibility to
      fluoroquinolones in NTS in Korea. To our knowledge, this is the first report of
      occurrence of aac(6')-Ib-cr gene among NTS in Korea. The spread of NTS carrying
      aac(6')-Ib-cr is of serious concern and should be carefully monitored.

PMID- 21877931
TI  - Thyroid cancer incidence in highly observant Jewish neighborhoods in metropolitan
      New York City.
AB  - BACKGROUND: Thyroid cancer incidence in New York State has increased rapidly in
      recent years, particularly in New York City and its surrounding metropolitan
      area. In 2007 among white non-Hispanics, incidence rates were about 40% higher in
      the New York City metropolitan area than in the rest of the state. Here we
      explore the extent to which living in neighborhoods with a high percentage of
      highly observant Jews may be associated with this pattern. METHODS: We identify
      neighborhoods with concentrations of highly observant Jewish persons based on the
      use of Yiddish among children and the location of Orthodox synagogues. Thyroid
      cancer risk is modeled as a function of living in such a neighborhood, adjusting
      for age, sex, and other factors. The model was repeated for small (<2 cm) and
      large (>=2 cm) tumors to assess the role of diagnostic improvements in driving
      the spatial-temporal patterns. RESULTS: A moderate association with thyroid
      cancer was found among those living in Jewish neighborhoods and downstate New
      York. A lesser association was found among those who live in neighborhoods of
      high levels of people born in Russia, Belarus, or Ukraine. Similar elevated rate
      ratios were seen for small and large tumors in Jewish neighborhoods, providing
      evidence against differences in diagnostic practices in this group. Smaller
      tumors were more pronounced among women and persons diagnosed more recently.
      CONCLUSIONS: The associations found do not seem to be diagnostically driven, but
      rather due to environmental, genetic, or cultural factors in the highly observant
      population of New York State.

PMID- 21877930
TI  - Agar disk diffusion and automated microbroth dilution produce similar
      antimicrobial susceptibility testing results for Salmonella serotypes Newport,
      Typhimurium, and 4,5,12:i-, but differ in economic cost.
AB  - Data generated using different antimicrobial testing methods often have to be
      combined, but the equivalence of such results is difficult to assess. Here we
      compared two commonly used antimicrobial susceptibility testing methods,
      automated microbroth dilution and agar disk diffusion, for 8 common drugs, using
      222 Salmonella isolates of serotypes Newport, Typhimurium, and 4,5,12:i-, which
      had been isolated from clinical salmonellosis cases among cattle and humans.
      Isolate classification corresponded well between tests, with 95% overall category
      agreement. Test results were significantly negatively correlated, and Spearman's
      correlation coefficients ranged from -0.98 to -0.38. Using Cox's proportional
      hazards model we determined that for most drugs, a 1 mm increase in zone diameter
      resulted in an estimated 20%-40% increase in the hazard of growth inhibition.
      However, additional parameters such as isolation year or serotype often impacted
      the hazard of growth inhibition as well. Comparison of economical feasibility
      showed that agar disk diffusion is clearly more cost-effective if the average
      sample throughput is small but that both methods are comparable at high sample
      throughput. In conclusion, for the Salmonella serotypes and antimicrobial drugs
      analyzed here, antimicrobial susceptibility data generated based on either test
      are qualitatively very comparable, and the current published break points for
      both methods are in excellent agreement. Economic feasibility clearly depends on
      the specific laboratory settings, and disk diffusion might be an attractive
      alternative for certain applications such as surveillance studies.

PMID- 21877932
TI  - Bioinformatics support the possible triggering of autoimmune thyroid diseases by
      Yersinia enterocolitica outer membrane proteins homologous to the human
      thyrotropin receptor.

PMID- 21877933
TI  - Papillary thyroid carcinoma in Peutz-Jeghers syndrome.
AB  - BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare dominantly inherited disease
      characterized by the association of gastrointestinal hamartomatous polyposis,
      mucocutaneous hyperpigmentation, and increased risk of cancer at different target
      organs. Its occurrence with differentiated thyroid cancer, particularly papillary
      thyroid carcinoma (PTC), even if rare, has been described. SUMMARY: We here
      present a case of PTC observed in a PJS patient and a review of the literature
      aiming at discussing the utility of thyroid surveillance in the management of
      these patients. A 22-year-old woman presenting with hyperpigmented lesions of the
      lips and hamartomatous polyps in the stomach, duodenum, jejunum, and ileum,
      leading to the suspicion of PJS, was submitted to genetic analysis. Mutation
      scanning of the Liver Kinase B1 (LKB1) gene identified the presence of the
      truncating mutation E265X, thus confirming the clinical diagnosis. Beside the
      endoscopic, radiologic, and echographic evaluations required by the standard
      surveillance guidelines, the patient had a neck ultrasound (US), which showed a
      5*4*6 mm hypoechoic nodule in the right thyroid lobe. The nodule contained
      microcalcifications and a perinodular vascular pattern. The cytological
      preparations derived from US-guided fine-needle aspiration biopsy of the nodule
      demonstrated the presence of PTC. The patient underwent a video-assisted total
      thyroidectomy and the histological examination revealed a follicular variant of
      papillary microcarcinoma. Radioactive iodine therapy was not performed because of
      the small size of the lesion. The patient was started on levothyroxine therapy to
      keep the serum thyrotropin levels suppressed. Both the sequencing and the
      multiplex ligation-dependent probe amplification analysis could not identify any
      LKB1 mutation in the tumor specimen, and the methylation-specific polymerase
      chain reaction assay excluded hypermethylation of the LKB1 promoter as the
      mechanism of inactivation for the remaining normal allele in the tumor.
      CONCLUSIONS: Although other mechanisms of LKB1 silencing may be responsible for
      its inactivation in the thyroid cancer, we cannot rule out that the occurrence of
      thyroid carcinoma could be a coincidental finding in this patient. However, the
      case here presented suggests that US of the thyroid could possibly become an
      integral part of the evaluation and the follow-up program adopted for PJS
      patients.

PMID- 21877934
TI  - A taller-than-wide shape in thyroid nodules in transverse and longitudinal
      ultrasonographic planes and the prediction of malignancy.
AB  - BACKGROUND: A "taller-than-wide" shape is associated with thyroid malignancy, but
      taller-than-wide in which plane is most accurate is unclear. We determined in
      which ultrasonography (US) plane a taller-than-wide shape is most predictive of
      malignancy. METHODS: A total of 471 thyroid nodules from 435 patients were
      studied. The final diagnosis was based on histopathology in 145 nodules in 120
      patients, and cytology in the remaining patients. A taller-than-wide shape was
      defined as a ratio of >=1, calculated by dividing the anteroposterior diameter by
      the transverse diameter. Three criteria were formulated as follows: criterion 1,
      a taller-than-wide in any plane as a suspicious feature; criterion 2, that in the
      transverse plane; criterion 3, that in the longitudinal plane. The sensitivity,
      specificity, positive predictive value, negative predictive value, and area under
      the receiver operating characteristic curve (Az) were compared among the three
      criteria. RESULT: Of the 471 lesions, 125 (26.5%) were classified as malignant,
      and 346 (73.5%) were classified as benign. Criterion 1 showed high sensitivity
      (68%) and negative predictive value (87.7%), whereas criteria 2 and 3 showed high
      specificity (83.5% and 94.5%, respectively). The Az vale of criterion 1 was
      significantly higher than criteria 2 and 3 (p values = 0.0061 and 0.0362,
      respectively). CONCLUSIONS: A taller-than-wide shape was a useful US feature for
      predicting thyroid malignancy. Criterion 1, a taller-than-wide shape in either
      transverse or longitudinal plane, was most accurate and sensitive for predicting
      thyroid malignancy among the three criteria.

PMID- 21877935
TI  - Risk for progression to overt hypothyroidism in an elderly Japanese population
      with subclinical hypothyroidism.
AB  - BACKGROUND: Few population-based studies report the changes with time in thyroid
      function tests in patients with subclinical hypothyroidism. We compared the risk
      for developing overt hypothyroidism in patients with subclinical hypothyroidism
      and euthyroid controls from the same population of elderly Japanese. We also
      sought associations of selected parameters with the development of overt
      hypothyroidism in the subclinical hypothyroid and euthyroid groups. METHODS: We
      measured thyrotropin (TSH) and free thyroxine (T4) levels at baseline
      examinations performed from 2000 to 2003 in the cohort of Japanese atomic-bomb
      survivors and identified 71 patients with spontaneous subclinical hypothyroidism
      (normal free T4 and TSH >4.5 mIU/L without a history of thyroid treatment, mean
      age 70 year) and 562 euthyroid controls. We re-examined TSH and free T4 levels an
      average of 4.2 years later (range, 1.9-6.9). RESULTS: The risk for progression to
      overt hypothyroidism was significantly increased in subclinical hypothyroid
      patients (7.0%) compared with control subjects (1.6%) after adjusting for age and
      sex (odds ratio, 4.56; p=0.009). Higher baseline TSH levels were associated with
      progression from subclinical to overt hypothyroidism (p=0.02) in the multivariate
      analysis, including age, sex, antithyroid peroxidase antibody, and
      ultrasonography (US) findings. The analysis using binary TSH data suggested that
      a TSH level >8 mIU/L was a predictive value for development of overt
      hypothyroidism (p=0.005). On the other hand, serum TSH levels spontaneously
      normalized in 38 (53.5%) of the patients with subclinical hypothyroidism. In the
      multivariate analysis, normalization of TSH levels was associated with lower
      baseline TSH levels (p=0.004) and normal and homogenous thyroid US findings
      (p=0.04). Atomic-bomb radiation dose was not associated with subclinical
      hypothyroidism or its course. CONCLUSIONS: Subclinical hypothyroidism was four
      times more likely to be associated with development of overt hypothyroidism than
      euthyroid controls in the sample population of Japanese elderly. TSH levels in
      half of the patients normalized spontaneously when assessed after an average
      follow-up period of 4.2 years. Baseline TSH level and thyroid US findings are
      potential predictors of future thyroid function in subclinical hypothyroidism.

PMID- 21877936
TI  - Neutrophil phenotypic characteristics in children with congenital asplenia and
      splenectomized for hereditary spherocytosis.
AB  - The spleen plays an important role in the granulocyte homeostasis due to such
      mechanisms as pooling, elimination of senescent cells and regulatory effects on
      granulocyte renewal in the bone marrow. The expression profile of granulocyte
      receptors was tested in children with congenital asplenia, and splenectomized for
      spherocytosis. Receptors tested included those appearing with maturation (CD16,
      CD11b, CD11c, TREM-1), disappearing (CD54, CD49d, CD64) and maintained during
      maturation (CD11a, CD45). In general, we found that the circulating granulocyte
      pool in the asplenic patients had phenotypical features of highly matured but not
      apoptotic neutrophils with a significantly elevated expression of CD16
      (CD16(high)), tendency to a lower expression of CD45 (CD45(low)) and an unchanged
      expression of CD64 (and other markers indicating systemic inflammatory
      reactions). The high fluorescence intensity of CD11b,c, and TREM-1 in the
      congenital asplenia may indicate a potentially elevated pro-inflammatory status
      of granulocytes, possibly due to the low activity of vagus nerve and spleen
      dependent cholinergic anti-inflammatory pathway.

PMID- 21877937
TI  - Mycobacterium tuberculosis Beijing genotype induces differential cytokine
      production by peripheral blood mononuclear cells of healthy BCG vaccinated
      individuals.
AB  - Members of the Mycobacterium tuberculosis (Mtb) Beijing genotype are a major
      concern due to their high prevalence in tuberculosis patients and their high rate
      of multi-drug resistance. Although it has been shown that Beijing modifies
      macrophage behavior, little is known about how this genotype could affect the
      cellular immune response. In order to address this issue, peripheral blood
      mononuclear cells (PBMC) from healthy BCG vaccinated individuals were stimulated
      with protein extracts from three Mycobacterium tuberculosis genotypes: Canetti,
      H37Rv and Beijing evaluating T cell proliferation and cytokine production. In
      this system both CD4+ and CD8+ proliferated in a similar manner independently of
      the Mtb genotype used for stimulation. Regarding cytokines, all strains induced
      similar levels of IFN-gamma, but were unable to induce IL-4 and TGF-beta.
      Contrasting, Canetti strain induced lower production of IL-10, TNF-alpha and IL
      12 compared to H37Rv and Beijing. Interestingly, PBMC stimulated with the Beijing
      strain produced the highest levels of IL-12 and IL-10 than those stimulated with
      other strains. This differential cytokine expression could affect the
      pathogenesis induced by Beijing strain through the modulation of inflammatory
      process in the host, but the precise mechanisms by which this cytokine
      environment affects the Beijing strain pathogenesis needs further
      characterization.

PMID- 21877938
TI  - Cisplatin restores TRAIL apoptotic pathway in glioblastoma-derived stem cells
      through up-regulation of DR5 and down-regulation of c-FLIP.
AB  - Glioblastoma-derived stem cells (GSCs) are responsible for the cancer resistance
      to therapies. We show here that GSC-enriched neurospheres are resistant to the
      treatment of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) due
      to the insufficient expression of the death receptor DR4 and DR5 and the
      overexpression of cellular Fas-associated death domain-like interleukin-1beta
      converting enzyme-inhibitory protein (c-FLIP). However, treatment with cisplatin
      leads to the upregulation of DR5 and downregulation of c-FLIP and restores TRAIL
      apoptotic pathway in the neurospheres. This study suggests that the combined
      treatment of TRAIL and cisplatin can induce apoptosis in GSCs and thus provide an
      effective treatment of glioblastomas.

PMID- 21877939
TI  - Development of new spontaneous metastatic heterotopic model of lewis lung
      carcinoma imaged by GFP expression.
AB  - Many studies have demonstrated the importance of spontaneous metastases in cancer
      research. Until now, we still had only a few spontaneous metastatic models with
      high occurrence rate of metastasis in distant lymph and visceral tissues. We
      report a syngeneic heterotopic metastatic model using the Lewis lung cancer cell
      line with high metastatic ratio in C57BL/6 mice after transplantation by
      injection of cancer cells and without surgical intervention. Metastatic process
      was declared for each mouse in two groups ?sacrificed 3 or 5 weeks after
      subcutaneous (s.c.) injection of the tumor cells into the dorsal side of the
      tail. The total number of metastases was counted as the sum of observed
      macrometastases. Our model produced produced a 100% rate of spontaneous lymphatic
      and visceral metastases after a simple injection transplantation into the
      heterotopic site. In mice with large primary tumors which are non-lethal,
      visceral and lymph macrometastases were observed. Tumor volume correlated
      linearly not only with the tumor growth time, but also with the number of
      metastases in lymph nodes and organs. This new metastatic model could be useful
      for studying the metastasis mechanism and for developing therapy for lymph and
      visceral metastases.

PMID- 21877940
TI  - Prescription drug misuse among Asian-American adults: results from a national
      survey.
AB  - Asians have low levels of substance use compared with other groups in the United
      States. Given the increase in Asian population, we believe it is important to
      study substance use in this population. Data from the 2002-2003 National Latino
      and Asian American Study are examined to address two questions. First, which
      Asian ethnic subgroup is at greatest risk for prescription drug misuse? Second,
      is acculturation significantly correlated with prescription drug misuse among
      Asians? Findings indicate that Filipinos are at the greater risk for prescription
      drug misuse. Also, Asians who are more acculturated are at greater risk for
      prescription drug misuse.

PMID- 21877941
TI  - Circadian and seasonal responses in Indian weaver bird: subjective interpretation
      of day and night depends upon both light intensity and contrast between
      illuminations.
AB  - This study investigated whether changes in illumination modify perception of day
      and night conditions in a diurnal species, the Indian weaver bird. Birds were
      initially subjected to a 12-h light:12-h dark regime (12L:12D; L=20 lux, D =0.5
      lux). After every 2 wks, the combinations of light illumination in L and D phases
      were changed as follows: 20:2 lux, 20:5 lux, 20:10 lux, 20:20 lux, 20:100 lux,
      and 20:200 lux. Finally, birds were released into dim constant light (0.5 lux)
      for 2 wks to determine the phase and period of the circadian activity rhythm.
      They were also laparotomized at periodic intervals to examine the effects of the
      light regimes on the seasonal testicular cycle. All individuals showed a
      consistently similar response. As evident by the activity pattern under these
      light regimes, both in total activity during contrasting light phases and during
      the 2?h in the beginning and end of first light phase, birds interpreted the
      period of higher light intensity as day, and the period of lower intensity as the
      night. During the period of similar light intensity, i.e., under LL, birds free
      ran with a circadian period ( ~ 24 h). In bright LL (20 lux), the activity rhythm
      was less distinct, but periodogram analysis revealed the circadian period for the
      group as 24.46 (+/-) 0.41 h (mean???SE). However, in dim LL at the end of the
      experiment, all birds exhibited a circadian pattern with average period of 25.52
      (+/-) 0.70 h. All birds also showed testicular growth and regression during the
      16-wks study. It is suggested that weaver birds interpret day and night
      subjectively based on both the light intensity and contrast between illuminations
      during two phases over the 24 h.

PMID- 21877942
TI  - Pure erythroid leukemia following precursor B-cell lymphoblastic leukemia.
AB  - Therapy-related acute myeloid leukemia is an unfortunate sequel to current
      multimodal intensive chemotherapy. The patient described was diagnosed with pure
      erythroleukemia, AML-M6b, during therapy for precursor B-cell acute lymphoblastic
      leukemia. To the best of our knowledge, this is the first report of this unusual
      association.

PMID- 21877943
TI  - Factors influencing the use of outcome measures in physical therapy practice.
AB  - Use of outcome measures in physical therapy practice is central to evaluating the
      effectiveness of treatment interventions, providing accountability and addressing
      quality of physical therapy programs. There is limited discussion on barriers and
      facilitators to using outcome measures in physical therapy practice. The purpose
      of this study was to identify factors that influence a physical therapist when
      deciding to use outcome measures in clinical practice. Participants were 21
      physical therapists, seven each from skilled nursing facilities, outpatient
      clinics, and inpatient rehabilitation facilities. A grounded theory approach was
      used for interview and data collection. Common themes were determined from the
      data and a theory developed to explain the rationale behind physical therapists'
      decisions to use or not use outcome measures in clinical practice. Three
      overlapping themes related to (1) concepts of time, (2) knowledge, and (3)
      facility culture were indentified as factors influencing the use of outcome
      measures. A fourth encompassing theme, professionalism, identified the value
      placed on the use of outcome measures in practice. Data revealed that therapists
      require more information on the outcome measures available, and this information
      needs to be easily accessible within the workplace. Therapists value information
      generated by using outcome measures in the clinical setting, but need information
      on what measures are available and psychometric properties. Information must be
      easily accessible and measures easy to use. Newer graduates and recent learners
      have a foundation in the use of outcome measures, but more needs to be done in
      the clinic and through continuing education to promote increased use and
      understanding.

PMID- 21877944
TI  - The effect of a dietary carbohydrase enzyme system on blood glucose levels when
      combined with foods of varying glycemic index in male Sprague-Dawley rats.
AB  - Extensive research has shown that physical performance and recovery can be
      improved by maintaining or enhancing glucose availability. Carbogen((r)) (Triarco
      Industries, Wayne, NJ, USA), a patented dietary fungal carbohydrase enzyme
      system, converts complex carbohydrates and fiber into simpler carbohydrates when
      ingested. Supplementing the enzymatic digestion of complex carbohydrates and
      fiber that may be digested very slowly or not at all in vivo may increase the
      availability of glucose. This may be reflected by increased absorption rates and
      higher measurable levels of whole blood glucose (WBG) that may be bioavailable
      for extended energy production. These preliminary investigations evaluate the
      ability of Carbogen to produce a rapid and more sustained increase in WBG levels
      when combined with a variety of food substrates commonly used by athletes and non
      athletes to increase levels of physical activity. To investigate this, food
      substrates having a low, moderate, or high glycemic index (GI) with various
      amounts of total carbohydrates and dietary fiber were used. The individually
      tested substrates include soy nuts, cooked pasta, meal replacement bars, a
      nutrition shake, and a carbohydrate sports supplement. The investigations
      presented here consist of seven separate preclinical rat feasibility studies
      conducted over a period of approximately 12 months. The collective results
      presented here identify specific attributes of a category of food substrates
      common to sports nutrition enthusiasts that may significantly increase WBG levels
      over an extended time when dosed with Carbogen. Specifically, using Carbogen with
      a food substrate having a low or moderate GI and containing dietary fiber may
      increase the rate of glucose absorption and maintain significant increases in WBG
      levels.

PMID- 21877945
TI  - Antioxidant, hepatoprotective, and ameliorative effects of methanolic extract of
      leaves of Grewia mollis Juss. on carbon tetrachloride-treated albino rats.
AB  - The methanolic extract of Grewia mollis leaves was evaluated in vivo for its
      antioxidant and hepatoprotective properties. Oxidative stress was induced in rats
      by administering carbon tetrachloride (CCl(4)) intraperitoneally at a dose of 0.6
      mL/kg, whereas the crude plant extract and standard antioxidant (vitamin E) were
      administered at a dose of 5 mg/kg and 50 mg/kg, respectively. The effect of G.
      mollis crude extracts and vitamin E on malondialdehyde (MDA) and liver function
      parameters such as protein, bilirubin, aspartate aminotransferase, and alanine
      aminotransferase were measured spectrophotometrically. The methanolic extract of
      G. mollis leaves and vitamin E showed a significant (P<.05) hepatoprotective
      potential by lowering the serum levels of bilirubin, aspartate aminotransferase,
      and alanine aminotransferase and decreasing MDA levels in rats pretreated or post
      treated with CCl(4). Based on these results, it is concluded that G. mollis
      leaves contain potent antioxidant compounds that could offer protection against
      hepatotoxicity as well as ameliorate preexisting liver damage and oxidative
      stress conditions.

PMID- 21877946
TI  - Cytotoxic, trypanocidal, and antifungal activities of Eugenia jambolana L.
AB  - Chagas' disease, caused by Trypanosoma cruzi, is considered a public health
      problem. Nowadays, chemotherapy is the only available treatment for this disease,
      and the drugs currently used, nifurtimox and benzonidazole, present high toxicity
      levels. Alternatives for replacing these drugs are natural extracts from Eugenia
      jambolana, a plant used in traditional medicine because of its antimicrobial and
      biological activities. An ethanol extract from E. jambolana was prepared. To
      research in vitro anti-epimastigote activity, T. cruzi CL-B5 clone was used.
      Epimastigotes were inoculated at a concentration of 1*10(5)/mL in 200 MUL of
      tryptose-liver infusion. For the cytotoxicity assay J774 macrophages were used.
      To examine antifungal activity, Candida albicans, Candida tropicalis, and Candida
      krusei were used. This is the first record of trypanocide activity for E.
      jambolana. The effective concentration capable of killing 50% of the parasites
      was 56.42 MUg/mL. The minimum inhibitory concentration was <=1,024 MUg/mL.
      Metronidazole showed a potentiation of its antifungal effect when combined with
      the ethanol extract of E. jambolana. Thus our results indicate that E. jambolana
      could be a source of plant-derived natural products with anti-epimastigote and
      antifungal modifying activity with moderate toxicity.

PMID- 21877947
TI  - [Dictyostelium discoideum: a model for the study of bacterial virulence].
AB  - The amoeba Dictyostelium discoideum, a bacterial predator, has emerged as a
      valuable tool for studying bacterial virulence. All its features make this
      unicellular eukaryote a versatile model organism. It can be used to study
      virulence factors of pathogenic bacteria as well as host elements involved in
      resistance to pathogens. The virulence of more than 20 bacterial species
      pathogenic for humans or animals has been studied using D. discoideum so far.
      These bacteria are either extracellular or intracellular pathogens. This review
      presents an overview of the question, with special emphasis on the reasons why D.
      discoideum is a suitable host model to study bacterial virulence, as well as on
      the type of information on host-pathogen relationship this amoeba can provide.

PMID- 21877948
TI  - Antioxidant and cytotoxic activity of the wild edible mushroom Gomphus clavatus.
AB  - The fruiting bodies of the edible mushroom Gomphus clavatus (Family Gomphaceae)
      were collected from the wild and extracted with solvents of increasing polarity.
      Crude extracts were evaluated for their total phenolic content, their antioxidant
      capacity, and their cytotoxic activity against MCF-7 and PC-3 cancer cell lines.
      Concerning total phenolics and antioxidant activity, the methanol extract showed
      the most potent radical scavenging activity with inhibition of 45.5% of 1,1
      diphenyl-2-picrylhydrazyl at 3 mg/mL. Further chemical investigation of the
      methanol extract led to the isolation and identification of nine compounds, among
      them four ergosterol derivatives. Concerning cytotoxicity, the dichloromethane
      (DCM) extract showed the most interesting activity, with half-maximal inhibitory
      concentration (IC(50)) values of 55.3 and 49.0 MUg/mL in the MCF-7 and PC-3 cell
      lines, respectively. Further investigation of the DCM extract lead to the
      identification of methyl esters of fatty acids and the isolation of four fatty
      acids and three ergosterol derivatives. Ergosterol peroxide (compound 6) was one
      of the most active constituents, with IC(50) values of 35.8 MUM and 30.6 MUM for
      MCF-7 and PC-3 cells, respectively, suggesting that the cytotoxic activity of the
      crude extract could be at least partly attributed to the presence of ergostan
      derivatives. Those findings suggest that G. clavatus can be considered as a
      medicinal food with antioxidant and chemopreventive activities.

PMID- 21877949
TI  - Indole-containing fractions of Brassica rapa inhibit inducible nitric oxide
      synthase and pro-inflammatory cytokine expression by inactivating nuclear factor
      kappaB.
AB  - In an attempt to identify bioactive natural products with anti-inflammatory
      activity, we evaluated the anti-inflammatory potential of the indole-containing
      fraction from the roots of Brassica rapa (IBR) (Family Brassicaceae) and the
      underlying mechanisms. Initially, we examined the inhibitory effect of IBR on the
      production of pro-inflammatory mediators in vitro and then evaluated its in vivo
      anti-inflammatory effects. IBR was found to concentration-dependently reduce the
      productions of nitric oxide, tumor necrosis factor-alpha (TNF-alpha), and
      interleukin-6 (IL-6) in lipopolysaccharide (LPS)-induced macrophages. Consistent
      with these findings, IBR suppressed the LPS-induced expressions of inducible
      nitric oxide synthase (iNOS) at the protein level and of iNOS, TNF-alpha, and IL
      6 at the mRNA level. Furthermore, IBR attenuated LPS-induced DNA-binding
      activities of nuclear factor-kappaB (NF-kappaB), and this was accompanied by a
      parallel reduction in the degradation and phosphorylation of inhibitory
      kappaBalpha and, consequently, by a reduction in the nuclear translocation of the
      p65 subunit of NF-kappaB. In addition, treatment with IBR inhibited carrageenan
      induced paw edema in rats and acetic acid-induced writing response in mice. Taken
      together, our data suggest that the expressional inhibitions of iNOS, TNF-alpha,
      and IL-6 caused by an attenuation of NF-kappaB activation are responsible for the
      anti-inflammatory and antinociceptive activity of IBR.

PMID- 21877951
TI  - Short-term study on the effects of rosemary on cognitive function in an elderly
      population.
AB  - Rosemary (Rosmarinus officinalis L.) has traditional reputations that justify
      investigation for a potential role in reducing widespread cognitive decline in
      the elderly. A randomized, placebo-controlled, double-blinded, repeated-measures
      crossover study was conducted to investigate possible acute effects of dried
      rosemary leaf powder on cognitive performance. Twenty-eight older adults (mean
      age, 75 years) were tested using the Cognitive Drug Research computerized
      assessment system 1, 2.5, 4, and 6 hours following a placebo and four different
      doses of rosemary. Doses were counterbalanced, and there was a 7-day washout
      between visits. There was a biphasic dose-dependent effect in measures of speed
      of memory: the lowest dose (750 mg) of rosemary had a statistically significant
      beneficial effect compared with placebo (P=.01), whereas the highest dose (6,000
      mg) had a significant impairing effect (P<.01). There were significant
      deleterious effects on other measures of cognitive performance, although these
      were less consistent. Speed of memory is a potentially useful predictor of
      cognitive function during aging. The positive effect of the dose nearest normal
      culinary consumption points to the value of further work on effects of low doses
      over the longer term.

PMID- 21877950
TI  - Phenolic compounds and biological activity of Kitaibelia vitifolia.
AB  - This study was aimed at evaluating the antioxidant activity and efficacy of the
      ethanolic extract of the endemic plant species Kitaibelia vitifolia in inhibiting
      the growth of selected fungi and bacteria. Antimicrobial activity was tested
      using the broth dilution procedure for determination of minimum inhibitory
      concentration (MIC). MICs were determined for eight selected indicator strains.
      The highest susceptibility to K. vitifolia ethanolic extract among the bacteria
      tested was exhibited by Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC
      25923, and Klebsiella pneumoniae ATCC 13883 (MIC=15.62 MUg/mL), followed by
      Escherichia coli ATCC 25922 and Proteus mirabilis ATCC 14153 (MIC=31.25 MUg/mL),
      and Proteus vulgaris ATCC 13315 (MIC=62.50 MUg/mL). Of the fungi, Candida
      albicans ATCC 10231 (MIC=15.62 MUg/mL) showed the highest susceptibility, and
      Aspergillus niger ATCC 16404 (MIC=31.25 MUg/mL) had the lowest. Results showed
      that K. vitifolia extract possesses antioxidant activity, with total antioxidant
      capacity of 75.45+/-0.68 MUg of ascorbic acid/g and 50% inhibition concentration
      values of 47.45+/-0.55 MUg/mL for 2,2-diphenyl-1-picrylhydrazyl free radical
      scavenging activity, 35.35+/-0.68 MUg/mL for inhibitory activity against lipid
      peroxidation, 95.25+/-0.52 MUg/mL for hydroxyl radical scavenging activity, and
      31.50+/-0.35 MUg/mL for metal chelating activity. Total phenolics, flavonoids,
      condensed tannins, and gallotannins were 85.25+/-0.69 mg of gallic acid (GA)/g,
      45.32+/-0.55 mg of rutin/g, 54.25+/-0.75 mg of GA/g, and 41.74+/-0.55 mg of GA/g,
      respectively. The phenolic composition of K. vitifolia extract was determined by
      high-performance liquid chromatography. Rosmarinic acid was found to be the
      dominant phenolic compound of the extract.

PMID- 21877952
TI  - In vitro fermentation characteristics of whole grain wheat flakes and the effect
      of toasting on prebiotic potential.
AB  - Population studies have shown a positive correlation between diets rich in whole
      grains and a reduced risk of developing metabolic diseases, like diabetes,
      cardiovascular disease, and certain cancers. However, little is known about the
      mechanisms of action, particularly the impact different fermentable components of
      whole grains have on the human intestinal microbiota. The modulation of microbial
      populations by whole grain wheat flakes and the effects of toasting on digestion
      and subsequent fermentation profile were evaluated. Raw, partially toasted, and
      toasted wheat flakes were digested using simulated gastric and small intestinal
      conditions and then fermented using 24-hour, pH-controlled, anaerobic batch
      cultures inoculated with human feces. Major bacterial groups and production of
      short-chain fatty acids were compared with those for the prebiotic oligofructose
      and weakly fermented cellulose. Within treatments, a significant increase (P<.05)
      in bifidobacteria numbers was observed upon fermentation of all test
      carbohydrates, with the exception of cellulose. Toasting appeared to have an
      effect on growth of lactobacilli as only fermentation of raw wheat flakes
      resulted in a significant increase in levels of this group.

PMID- 21877953
TI  - Composition and antioxidant activity of water-soluble polysaccharides from Tuber
      indicum.
AB  - Crude water-soluble Chinese truffle Tuber indicum polysaccharide (TIP) was
      extracted from the fruiting bodies with water and then successively purified by
      DEAE-cellulose 52 and Sephadex G-100 column chromatography, yielding two major
      polysaccharide fractions: TIP1-1 and TIP2-1. High-performance gel permeation
      chromatography analysis showed that the average molecular sizes of TIP1-1 and
      TIP2-1 were approximately 1.75*10(4) Da and 5.73*10(3) Da, respectively.
      Monosaccharide component analysis by gas chromatography indicated that TIP1-1 was
      composed of mannose, glucose, galactose, and rhamannose in the respective molar
      ratio of 3.93:1.24:0.75:1.26 and that TIP2-1 contained mannose, glucose, and
      arabinose in the respective molar ratio of 5.27:1.44:0.43. The antioxidant
      activity analyses revealed that TIP1-1 and TIP2-1 possessed considerable
      antioxidant activity. Compared with TIP1-1, which has a higher molecular weight
      and contains no uronic acid, TIP2-1 exhibited a protective effect on PC12 cells
      injured by H(2)O(2) and a higher scavenging activity against free radicals. The
      relative effects of the lower molecular size, the presence of uronic acid, and
      the antioxidant activity of TIP2-1 appear to be significant. Accordingly, the
      Chinese truffle T. indicum might serve as an effective antioxidative healthcare
      food and source of natural antioxidants.

PMID- 21877954
TI  - Effects of Passiflora edulis (yellow passion) on serum lipids and oxidative
      stress status of Wistar rats.
AB  - The aim of this study was to evaluate the effects of Passiflora edulis f.
      flavicarpa Degener (yellow passion) juice on the lipid profile and oxidative
      stress status of Wistar rats. Adult male Wistar rats were divided in two groups
      (n=8 animals per group): the control group, which received water, and the treated
      group, which was given P. edulis juice (1,000 mg/kg). Both groups received by
      gavage treatment twice a day for 28 days. The treated group showed an increased
      high-density lipoprotein-cholesterol level and decreased low-density lipoprotein
      cholesterol and free fatty acid levels compared with the control group. Levels of
      triglycerides and and very low-density lipoprotein-cholesterol, superoxide
      dismutase activity, and total glutathione concentration were not statistically
      different between the two groups, but the thiobarbituric acid-reactive substances
      concentration (indicating lipid peroxidation) decreased in the treated group.
      These findings suggests that P. edulis juice in the experimental conditions used
      showed beneficial effects on lipid profile and improved lipid peroxidation in
      Wistar rats.

PMID- 21877956
TI  - Peroxisome proliferator activating receptor alpha and gamma polymorphisms and
      metabolic abnormalities in HIV-infected patients receiving highly active
      antiretroviral therapy: the ANRS CO8 APROCO-COPILOTE study.
AB  - Highly active antiretroviral therapy (HAART) is associated with fat
      redistribution and metabolic disorders. The present study was undertaken to
      evaluate the association between peroxisome proliferator activated receptor
      (PPAR)alpha and PPARgamma polymorphisms, two genes involved in lipid metabolism
      and adipocyte differentiation, and elements of the metabolic syndrome,
      lipodystrophy, or carbohydrate metabolism abnormalities in patients receiving
      HAART. The frequency distribution of rare alleles for PPARalpha (L162V) and
      PPARgamma (P12A and H449H) was compared using the chi square test in 363 HIV-1
      infected patients classified according to the presence or absence of the
      metabolic syndrome after 48 months of follow-up on their first PI-containing
      regimen. The P12A rare g allele was present in 12% patients with normal glucose
      metabolism, 11% patients with impaired glucose tolerance or impaired fasting
      glucose, and 35% patients with diabetes (p=0.014). The rare g allele for L162V
      was present in 14% of patients free of hypertriglyceridemia and in 7% patients
      with hypertriglyceridemia (p=0.04). The rare g allele for L162V was found in 15%
      of patients free of any sign of lipodystrophy and 8% with at least one sign of
      lipodystrophy (p=0.04) and the rare t allele for H449H was found in 14% of
      patients free of any sign of lipodystrophy and 23% of patients with at least one
      sign of lipodystrophy (p=0.05). There was no convincing association between any
      polymorphism of PPARalpha and PPARgamma and each individual component of the
      metabolic syndrome, except for the relationship of the P12A polymorphism with
      diabetes. Confirmatory studies on a larger number of individuals are needed.

PMID- 21877957
TI  - Functions of nonsuicidal self-injury among young women in residential care: a
      pilot study with the Swedish version of the Inventory of Statements about Self
      Injury.
AB  - Nonsuicidal self-injury (NSSI) refers to the direct and deliberate destruction of
      one's own body tissue in the absence of lethal intent. The Inventory of
      Statements about Self-Injury (ISAS) is a recently developed instrument that taps
      both the frequency of different forms of NSSI and the self-perceived functions of
      the behaviour. The purpose of the present pilot study was to use the ISAS to
      study the functions of self-injury in a group of women with severe forms of NSSI
      who were treated within Swedish residential care settings and also to compare the
      patients' views with their therapists' views concerning these functions.
      Consistent with previous research, the patients reported intrapersonal functions
      (e.g. affect regulation and self-punishment) as more relevant than interpersonal
      functions (e.g. interpersonal influence and peer bonding). The therapists'
      ratings differed little from the patients' self-reports, although significant
      differences were found for some functions: The patients rated self-care and
      toughness as more important than the therapists did; the therapists, on the other
      hand, rated interpersonal influence and the marking of distress as more relevant
      than the patients did. Although the present study did not contain a full
      validation of the Swedish version of the ISAS, the results showed good internal
      consistency for the interpersonal and intrapersonal factors of the Swedish
      version.

PMID- 21877955
TI  - Involvement of single-nucleotide polymorphisms in predisposition to head and neck
      cancer in Saudi Arabia.
AB  - AIM: Individuals differ in their inherited tendency to develop cancer. This has
      been suggested to be due to genetic variations between individuals. Single
      nucleotide polymorphisms (SNPs) are the most common form of genetic variations
      found in the human population. The aim of this study was to investigate the
      association between 10 SNPs in genes involved in cell cycle control and DNA
      repair (p21 C31A, p53 G72C, ATM G1853A, XRCC1 G399A, XRCC3 C241T, Ku80 A2790G,
      DNA Ligase IV C9T, DNA-PKcs A3434G, TGF-beta T10C, MDM2 promoter T309G) and the
      risk to develop head and neck cancer. MATERIALS AND METHODS: A cohort of 407
      individuals (156 cancer patients and 251 controls) was included. DNA was
      extracted from peripheral blood. SNPs were genotyped by direct sequencing.
      RESULTS: Data showed significant allelic associations for p21 C31A (p=0.04; odds
      ratio [OR]=1.44; confidence interval [CI]: 1.02-2.03), Ku80 A2790G (p=0.04;
      OR=1.5; CI: 1.01-2.23), and MDM2 T309G (p=0.0003; OR=0.58; CI: 0.43-0.78) and
      head and neck cancer occurrence. Both cancer cases and controls were in Hardy
      Weinberg equilibrium. CONCLUSION: SNPs can be associated with head and neck
      cancer in the Saudi population. The p21 C31A, Ku80 A2790G, and MDM2 T309G SNPs
      could be used as genetic biomarkers to screen individuals at high cancer risk.

PMID- 21877958
TI  - Negative life experiences and the development of cluster C personality disorders:
      a cognitive perspective.
AB  - Early negative experiences have long been thought to play an important role in
      the development of personality disorders. Most of the literature regarding these
      early life experiences has focused on borderline personality disorder, with only
      occasional focus on other personality disorders. Utilizing cognitive theory of
      personality disorders (Beck et al., 2004), the authors conceptualize cluster C
      personality disorders (avoidant, dependent, and obsessive-compulsive). They then
      critically review the relevant literature on early negative life experiences and
      later development of these disorders to determine whether the theory is supported
      by the empirical data. The theory regarding avoidant and dependent personality
      disorders has limited support, whereas data relating to obsessive-compulsive
      personality disorder are much weaker. Implications and future research
      suggestions are discussed.

PMID- 21877959
TI  - Why do they exercise less? Barriers to exercise in high-anxiety-sensitive women.
AB  - Anxiety sensitivity (AS; fear of arousal sensations) is a risk factor for mental
      and physical health problems, including physical inactivity. Because of the many
      mental and physical health benefits of exercise, it is important to better
      understand why high-AS individuals may be less likely to exercise. The present
      study's aim was to understand the role of barriers to exercise in explaining
      lower levels of physical exercise in high-AS individuals. Participants were
      undergraduate women who were selected as high (n = 82) or low (n = 72) AS. High
      AS women participated in less physical exercise and perceived themselves as less
      fit than low-AS women. Mediation analyses revealed that barriers to exercise
      accounted for the inverse relationships between AS group and physical
      exercise/fitness levels. Findings suggest that efforts to increase physical
      exercise in at-risk populations, such as high-AS individuals, should not focus
      exclusively on benefits to exercise but should also target reasons why these
      individuals are exercising less.

PMID- 21877961
TI  - Failing those at ground zero ... again: American public health responses to AIDS
      and 9/11.

PMID- 21877962
TI  - Impairing loyalty: corporate responsibility for clinical misadventure.
AB  - A medical device manufacturer pays a surgeon to demonstrate a novel medical
      instrument in a live broadcast to an audience of specialists in another city. The
      surgical patient is unaware of the broadcast and unaware of the doctor's
      relationship with the manufacturer. It turns out that the patient required a
      different surgical approach to her condition-one that would not have allowed a
      demonstration of the instrument--and she later dies. The paper is an exploration
      of whether the manufacturer shares, along with the doctor, responsibility for the
      death of the patient. Three arguments for corporate responsibility are
      considered; two are criticized and the third is offered as sound.

PMID- 21877963
TI  - Foxes guarding the henhouse: systemic responsibility for corporate harms.

PMID- 21877964
TI  - Corporate moral culpability in health care: when the implications don't fit the
      crime.

PMID- 21877965
TI  - Does fortune foul fidelity?

PMID- 21877966
TI  - Blind spots.

PMID- 21877967
TI  - Understanding corporate responsibility: culture and complicity.

PMID- 21877968
TI  - Challenging the idea of corporate responsibility: physician's obligation to
      disclose information.

PMID- 21877969
TI  - Assessing the risk of ovarian hyperstimulation syndrome in egg donation:
      implications for human embryonic stem cell research.
AB  - Stem cell research has important implications for medicine. The source of stem
      cells influences their therapeutic potential, with stem cells derived from early
      stage embryos remaining the most versatile. Somatic cell nuclear transfer (SCNT),
      a source of embryonic stem cells, allows for understandings about disease
      development and, more importantly, the ability to yield embryonic stem cell lines
      that are genetically matched to the somatic cell donor. However, SCNT requires
      women to donate eggs, which involves injection of ovulation-inducing hormones and
      egg retrieval through laparoscopy or transvaginal needle aspiration. Risks from
      this procedure are fiercely debated, most notably risk of ovarian
      hyperstimulation syndrome (OHSS). This review examines risk of OHSS resulting
      from oocyte donation. We conclude that risk posed by OHSS in egg donation is not
      significant enough to warrant undue concern, and much of this can be eliminated
      when proper precautions are taken. This bears relevance to the future of stem
      cell research policymaking.

PMID- 21877970
TI  - A precautionary approach to oocyte donation for stem cell nuclear
      transplantation.

PMID- 21877971
TI  - Ethical concerns eliminated: safer stimulation protocols and egg banking.

PMID- 21877972
TI  - The conundrum of oocyte donation, human research, OHSS, and ethics.

PMID- 21877973
TI  - Reconsidering risk to women: oocyte donation for human embryonic stem cell
      research.

PMID- 21877974
TI  - Harmony and compensation for oocyte providers.

PMID- 21877975
TI  - Oocytes for research: reevaluating risks and compensation.

PMID- 21877976
TI  - Considering the risks to economically disadvantaged egg donors.

PMID- 21877977
TI  - Profile of trace elements in Parasol Mushroom (Macrolepiota procera) from
      Tucholskie Forest.
AB  - The aim of this study was to determine 19 elements contents and bioconcentration
      potential in fruiting bodies of Parasol Mushroom (Macrolepiota procera) collected
      from the Tucholskie Forest complex in Poland. Also discussed were Cd, Pb and Hg
      contents of edible caps in relation to the current regulatory standards. K, P and
      Mg were particularly abundant in caps and stipes, median values were 38-49, 13,
      and 1.6-1.6 mg/g dry weight, and followed by Ca, Na and Rb at 110-540, 44-240 and
      20-50 MUg/g dw, respectively. Concentrations of Al, Fe, Zn, Cu and Mn were from
      less than 50 to 180 MUg/g dw, while concentrations of other elements were ~l.0
      MUg/g dw or less. Cu, K, Ag, Cd, Na, Rb, Zn and Hg were bioconcentrated (BCF >1),
      while Al, Ba, Fe, Mn, Co, Sr, Pb and Cr were not bioaccumulated (BCF <1). Cd and
      Pb content of Parasol Mushroom's edible caps collected from some sites in the
      Tucholskie Forest exceed the maximum levels set in the EU for cultivated
      mushrooms.

PMID- 21877978
TI  - Parts-per-trillion LC-MS(Q) analysis of herbicides and transformation products in
      surface water.
AB  - The goal of this study was to develop a robust method of analyzing surface water
      samples for S-triazine herbicides, chloroacetanilide herbicides, and their
      transformation products (TPs) using solid-phase extraction (SPE) followed by
      liquid chromatograph-mass spectrometry (LC-MS) with electrospray ionization (ESI)
      by in-source collision-induced dissociation (ISCID) capability of an orthogonal
      electrospray ionization probe on a single quadrupole LC-MS system. The method
      developed here met the goals of the study and yielded estimated method detection
      limits (EMDLs) averaging 0.3 +/- 0.1 ng L(-1) for S-triazines and their TPs and
      0.7 +/- 0.4 ng L(-1) for chloroacetanilides and TPs. Spiked filtered river water
      yielded SPE recoveries ranging from 94.2 % +/- 4.8 % for S-triazines and TPs
      after eliminating three compounds with less that 65 % recovery from analysis and
      95.9 % +/- 19 % for chloroacetanilides and their TPs. The method was field-tested
      with filtered water samples collected from four sites over a four-month period.
      Detectible values of S-triazines and TPs ranged from 0.3 to 1540 ng L(-1) with a
      mean of 79.3 and a median of 19.4 ng L(-1). Detectible values for
      chloroacetanilides and TPs ranged from 0.31 to 3780 ng L(-1) with a mean of 252
      and a median of 25.6 ng L(-1). An additional goal was to determine if the method
      was useful for microbial degradation studies using native bacterial communities.
      The bacteria transformed atrazine (2-chloro-4-ethylamino-6-isopropylamino-S
      triazine) solely into 2-hydroxy atrazine (2-hydroxy-4-ethylamino-6-isopropylamino
      S-triazine) with concentrations of 78.4, 63.3 and 32.5 ng L(-1) after 12 days of
      incubation compared with 6.3 and 7.1 ng L(-1) for control dark and control
      sunlight respectively.

PMID- 21877979
TI  - Land application of tylosin and chlortetracycline swine manure: Impacts to soil
      nutrients and soil microbial community structure.
AB  - The land application of aged chortetracycle (CTC) and tylosin-containing swine
      manure was investigated to determine associated impacts to soil microbial
      respiration, nutrient (phosphorus, ammonium, nitrate) cycling, and soil microbial
      community structure under laboratory conditions. Two silty clay loam soils common
      to southeastern South Dakota were used. Aerobic soil respiration results using
      batch reactors containing a soil-manure mixture showed that interactions between
      soil, native soil microbial populations, and antimicrobials influenced CO(2)
      generation. The aged tylosin treatment resulted in the greatest degree of CO(2)
      inhibition, while the aged CTC treatment was similar to the no-antimicrobial
      treatment. For soil columns in which manure was applied at a one-time agronomic
      loading rate, there was no significant difference in soil-P behavior between
      either aged CTC or tylosin and the no-antimicrobial treatment. For soil-nitrogen
      (ammonium and nitrate), the aged CTC treatment resulted in rapid ammonium
      accumulation at the deeper 40cm soil column depth, while nitrate production was
      minimal. The aged CTC treatment microbial community structure was different than
      the no-antimicrobial treatment, where amines/amide and carbohydrate chemical
      guilds utilization profile were low. The aged tylosin treatment also resulted in
      ammonium accumulation at 40 cm column depth, however nitrate accumulation also
      occurred concurrently at 10 cm. The microbial community structure for the aged
      tylosin was also significantly different than the no-antimicrobial treatment,
      with a higher degree of amines/amides and carbohydrate chemical guild utilization
      compared to the no-antimicrobial treatment. Study results suggest that land
      application of CTC and tylosin-containing manure appears to fundamentally change
      microbial-mediated nitrogen behavior within soil A horizons.

PMID- 21877980
TI  - Optimization of analytical methods to improve detection of erythromycin from
      water and sediment.
AB  - Analytical methods to improve the detection of erythromycin in water and sediment
      were developed to optimize for erythromycin's recovery of extractable and bound
      residues from the aquatic environment. The objective of this study was to
      determine optimal recovery of erythromycin from water and sediment to improve its
      detection in environmental samples through solid-phase extraction (SPE) and
      sediment-extraction methods. SPE methods examined included previously reported
      methods for macrolide and sulfonamide antibiotics with erythromycin recoveries
      ranging from 75.5 % to 94.7 %. Extraction of erythromycin was performed from sand
      employing various solvents and buffers to determine the best method for
      extraction from two sandy loam pond sediments. Various extraction times were also
      examined, and all extraction procedures were performed in duplicate. The greatest
      recovery of (14)C-erythromycin in the Iowa sediment was 84 % using 0.3 M ammonium
      acetate at pH 4.2: acetonitrile (15:85, v/v) solution. The Oklahoma sediment
      yielded the greatest recovery of (14)C-erythromycin at 86.7 % with 0.3 M ammonium
      acetate at pH 7: acetonitrile (30:70, v/v) with a 60-minute shake time. The
      present results demonstrate improved extraction methods for enhancing the
      accuracy of erythromycin detection from environmental samples.

PMID- 21877981
TI  - Introduction.

PMID- 21877982
TI  - An evaluation of a client-centered case management program for elder abuse.
AB  - ABSTRACT Short-term outcomes of a case management program for competent,
      community-dwelling abused elderly persons were assessed. The intervention
      provided by Case Managers consisted of five components: (a) helping the client
      set long and short-term goals, (b) providing information about services and legal
      rights, (c) explaining and discussing options to decrease abuse, (d) supporting
      the client in deciding to take action or not, and (e) involving others in the
      plan of care. Retrospective data were collected from 26 client records.
      Intervention outcomes were assessed by determining the number of cases in which
      abuse was eliminated or decreased at case closure and the reasons for case
      closure. In 34.6% of the cases, abuse was completely eliminated, while in 30.8%
      of cases there was some improvement in the situation.

PMID- 21877983
TI  - The financial abuse of mentally incompetent older adults: a canadian study.
AB  - ABSTRACT This article reports the results of a pilot study on the financial abuse
      of mentally incompetent seniors. The objectives of the study were to: (1)
      establish the incidence of suspected financial abuse among the clientele of the
      Office of Public Trustee, Province of Manitoba, (2) identify the characteristics
      of mentally incompetent older adults most at risk, and (3) identify indicators of
      financial abuse. Approximately 20% of the cases opened in a one year period were
      under suspicion of abuse. Findings were consistent with those of other research
      projects on elder abuse, in general, showing an over-representation of women over
      the age of eighty as victims of financial abuse. Unpaid personal care home bills
      when money should have been available was the most common indicator. In addition
      to providing a list of indicators of financial abuse that are of potential use to
      professionals, devising prevention programs, practical implications for service
      providers are presented.

PMID- 21877984
TI  - Meeting the needs of abused older women? A british columbia and yukon transition
      house survey.
AB  - ABSTRACT Older women victims of violence by a partner or family member are more
      often categorized as victims of elder abuse, not victims of family violence.
      Their needs are assessed, if at all, by social and health service agencies, often
      with little knowledge or understanding of domestic violence, while domestic
      violence policy initiatives, advocacy, and services focus on younger women and
      children. A survey of domestic violence services in British Columbia and the
      Yukon found that women over 60 years of age were a very small fraction, generally
      less than two percent, of women served, and those 50 to 59 years of age were also
      substantially under-represented. Only four percent of respondents had special
      services for older women. Comments from respondents confirm that abused older
      women face enormous difficulties in trying to establish a safe and secure future.
      It was also evident that better interaction is needed between those providing
      support and advocacy for abused women, and those who provide health and social
      services for older persons. A majority of the shelters provided community
      education to a wide range of agencies. Most have only partial accessibility to
      women with mobility handicaps.

PMID- 21877985
TI  - The changing career of "elder abuse and neglect" as a social problem in Canada:
      learning from feminist frameworks?
AB  - ABSTRACT "Elder Abuse and Neglect" was constructed as a social problem by experts
      and has largely been a product of "expert" knowledge building and intervention.
      The idea of woman abuse as a social problem, on the other hand, originated with
      women themselves. The paper examines the changing social context in which some
      older people are currently seeking ownership of responses to mistreatment. It
      explores emerging criticisms of present constructions of "elder abuse and
      neglect" and the needs they imply, and links these to feminist frameworks. It
      then considers the appeal and utility of these frameworks for older women active
      in the fight against mistreatment.

PMID- 21877986
TI  - Mental health and criminal justice issues among perpetrators of elder abuse.
AB  - ABSTRACT Recent studies on elder abuse suggest that the pathology or impairment
      of the abuser may be a stronger predictor of elder abuse than characteristics of
      the victim. To examine the relationship between elder abuse, abuser pathology,
      and the criminal justice system, the New York City Department for the Aging
      (DFTA) undertook a survey of older victims of reported domestic abuse seeking
      assistance from the DFTA Elderly Crime Victims Resource Center. Preliminary
      findings from the survey indicate that impaired abusers were significantly
      younger than unimpaired abusers and more likely to live with their elderly
      victims, to be unemployed, and to have a history of involvement with the criminal
      justice system.

PMID- 21877987
TI  - The mistreatment of older adults: perpetrator-victim relationships and
      interventions.
AB  - ABSTRACT The characteristics of the mistreatment of older adults were
      investigated in a sample of 128 older adults identified as potential mistreatment
      cases in three community-based agencies in Quebec. Practitioners completed
      questionnaires to collect quantitative and qualitative data. The study also
      examined: (1) difficulties in identifying mistreatment, (2) interventions and
      outcomes, and (3) reasons for the refusal of services. The major finding (with
      important implications for practice) was the association between type of
      treatment and perpetrator relationship to victim. The harm reduction model is
      suggested as a useful approach to guide interventions.

PMID- 21877988
TI  - Unrecognized risks associated with new cervical screening guidelines for younger
      women.

PMID- 21877989
TI  - Solution densities and estimated total protein contents associated with
      inappropriate flotation of separator gel in different blood collection tubes.
AB  - CONTEXT: Clinical samples that have densities greater than that of separator gel
      in specimen tubes may exhibit gel flotation to the top of the specimen upon
      centrifugation. Inappropriate separator gel flotation can occur in specimens with
      high protein content. In automated analytical systems, gel flotation can lead to
      mechanical disruption and potential inaccurate result reporting upon aspiration
      into instrument sampling probes. OBJECTIVE: To determine the relative specimen
      densities and estimated total protein contents at which specimen gel flotation
      would occur upon centrifugation in commonly used commercial specimen tubes, a
      comparative study of separator gel density was initiated using prepared dextran
      solutions. DESIGN: Specific gravity of several dextran solutions was determined
      by direct hydrometry. The dextran solutions were introduced to serum and plasma
      lithium heparin BD Vacutainer specimen tubes manufactured by Becton, Dickinson
      and Company and into Vacuette specimen tubes manufactured by Greiner Bio-One
      containing separator gel. Following centrifugation the specimen tubes were
      examined for gel flotation. RESULTS: Flotation was observed at a lower dextran
      solution density for Greiner than for BD tubes in both serum and plasma separator
      gel specimen tubes. Additionally, some differences between specimen tube lots
      were observed for both BD and Greiner tubes. The total protein content in
      clinical samples that would result in gel flotation can be estimated for
      different specimen container types. CONCLUSIONS: Differences were observed for
      the gel separator specific gravity in different blood collection containers.
      Laboratories wishing to avoid problems with inappropriate gel flotation in high
      protein samples should consider these observations.

PMID- 21877990
TI  - Granulomatous dermatitis due to Malassezia sympodialis.
AB  - A 67-year-old man, with multiple skin lesions that appeared over 2 years, had
      biopsies that disclosed granulomatous dermatitis with associated small yeasts.
      The urinary antigen test results were negative for Histoplasma infection;
      cultures from the biopsies did not grow any fungi or other potential pathogens.
      The chest roentgenogram results were normal. Morphologic examination revealed
      features of a Malassezia species. Broad-range fungal polymerase chain reaction
      and DNA sequencing disclosed that the infecting fungus was Malassezia sympodialis
      , a lipid-dependent yeast. This report supports one other case report that
      Malassezia species may cause granulomatous dermatitis; in the previous case, the
      etiologic agent was Malassezia pachydermatis , a nonlipid-dependent species. We
      recommend the use of lipid-supplemented culture media for specimens from patients
      with granulomatous dermatitis because several Malassezia species are dependent on
      lipid; the absence of lipid supplementation in routine cultures likely explains
      the negative culture results for this patient. This, to our knowledge, is the
      first report of granulomatous dermatitis caused by M sympodialis.

PMID- 21877991
TI  - Genomic aberrations in salivary duct carcinoma arising in Warthin tumor of
      parotid gland: DNA microarray and HER2 fluorescence in situ hybridization.
AB  - Carcinoma arising from Warthin tumor is extremely rare. A 79-year-old man was
      admitted for a firm, well-defined, 5-cm left infra-auricular mass. Aspiration
      cytology showed many lymphohistiocytes and oncocytes in a proteinaceous
      background, compatible with Warthin tumor. A left superficial parotidectomy
      showed a solid mass around the cyst wall. The tumor cells of the solid area were
      arranged as infiltrative ducts with a few foci of malignant transformation.
      Virtual karyotyping disclosed a complex pattern of genetic aberrations with a
      focal amplification in 12q14-q21.2. This chromosomal region contains the MDM2
      (murine double minute) gene, which regulates p53 inactivation. HER2 fluorescence
      in situ hybridization showed a focal amplification. Subsequently, the patient
      underwent total parotidectomy and ipsilateral neck dissection for a recurrence.
      To our knowledge, this is the first case of salivary duct carcinoma arising from
      Warthin tumor. The essential molecular pathway has not been reported, we presume
      an important role of MDM2 amplification- P53 inactivation.

PMID- 21877992
TI  - Antiphospholipid antibody syndrome.
AB  - Antiphospholipid antibodies are directed against phospholipid-protein complexes
      and include lupus anticoagulant, anticardiolipin antibodies, and anti-beta-2
      glycoprotein I antibodies. Antiphospholipid antibody syndrome is a common cause
      of acquired thrombophilia and is characterized by venous or arterial
      thromboembolism or pregnancy morbidity and the presence of antiphospholipid
      antibodies. Antibodies should be demonstrable on at least 2 occasions separated
      by 12 weeks. Heterogeneity of the autoantibodies and absence of gold standard
      assays makes interpretation of laboratory results a challenge for both
      laboratorians and clinicians. This review discusses the key laboratory and
      clinical aspects of antiphospholipid antibody syndrome. Particular focus is given
      to lupus anticoagulant detection, in view of recently updated laboratory
      guidelines.

PMID- 21877993
TI  - Carcinoma of the breast with choriocarcinomatous features.
AB  - Choriocarcinomatous differentiation has been described in tumors arising from
      many organs including lung, rectum, colon, stomach, bladder, and rarely breast.
      Mammary carcinoma with choriocarcinomatous features is a rare variant of breast
      metaplastic carcinoma characterized by malignant cells morphologically resembling
      choriocarcinoma cells in which reactivity with human placental lactogen and human
      chorionic gonadotropin can be demonstrated by immunohistochemistry. The
      characteristic syncytiotrophoblast-like giant cells seen in these neoplasms are
      more commonly associated with moderately to poorly differentiated carcinomas with
      or without a clear-cut mesenchymal component. Most of the reported cases have
      behaved very aggressively. The reason for this poor prognosis remains unclear.
      Because of the small number of cases, special treatment protocols have not been
      developed and these patients are treated surgically and with the standard
      chemotherapeutic agents available for other types of carcinoma of the breast.
      Pathologically, these tumors must be distinguished from metastatic
      choriocarcinoma to the breast.

PMID- 21877997
TI  - Conatumumab: a novel monoclonal antibody against death receptor 5 for the
      treatment of advanced malignancies in adults.
AB  - INTRODUCTION: Advanced malignancies that are refractory to standard chemotherapy
      have few treatment options. Conatumumab is an investigational, fully human
      monoclonal agonist antibody directed at human death receptor DR5, which is
      expressed in multiple advanced cancers. AREAS COVERED: The rationale for the use
      of conatumumab based on in vitro, in vivo, Phase I, and Phase II data will be
      discussed. EXPERT OPINION: Conatumumab, at a dose of 20 mg/kg every 2 weeks, has
      demonstrated acceptable safety and tolerability in patients with advanced tumors
      based on available and published data. Further clinical trials are underway
      evaluating the use of conatumumab in combination with chemotherapeutic and
      targeted agents.

PMID- 21877996
TI  - The combined oral contraceptive pill containing drospirenone and ethinyl
      estradiol plus levomefolate calcium.
AB  - INTRODUCTION: Neural tube defects are the second most common congenital anomaly
      in the United States, although their incidence may be decreased by periconception
      folic acid supplementation. A new oral contraceptive containing drospirenone and
      ethinyl estradiol plus levomefolate calcium was formulated to decrease the risk
      of neural tube defects in pregnancies conceived while taking or shortly after
      discontinuing this pill. AREAS COVERED: Because of its novelty, very few studies
      have been performed to evaluate the efficacy, side effects and safety related to
      contraception, premenstrual dysphoric disorder and acne; therefore, literature
      evaluating similar contraceptives without levomefolate is reviewed. Additionally,
      we review studies evaluating the addition of levomefolate calcium to oral
      contraceptives containing 3 mg drospirenone and either 20 or 30 MUg ethinyl
      estradiol. To date, no study has been performed to evaluate the effect this new
      oral contraceptive has on reducing the incidence of neural tube defects. EXPERT
      OPINION: This new pill has similar contraceptive efficacy, side effect, safety
      and benefits profile to other drospirenone-containing contraceptives. While also
      approved to prevent neural tube defects, no studies validate this claim and
      physician time is better spent counseling women, regardless of contraceptive
      choice, on the importance of folic acid supplementation during the child-bearing
      years.

PMID- 21877999
TI  - Emerging viral infections in neonatal intensive care unit.
AB  - Nosocomial infections are the most important cause of morbidity and mortality
      among neonates and mostly in infants admitted to neonatal intensive care units
      (NICU). The total number of neonates who develop nosocomial infections per
      admission varies from 6.2 to 30%. The role of nosocomial virus infections is
      generally neglected in the actual epidemiologic scenario mostly due to the lack
      of data in the medical literature. Based on a worldwide database of health care
      associated outbreaks (http://www.outbreak-database.com) we performed an analysis
      of the incidence, type of pathogens and clinical features of neonatal viral
      outbreaks especially those reported in NICUs. We also describe, as an example of
      emerging virus in NICU, a Norovirus outbreak along with clinical presentation
      that varies from mild to moderate clinical symptoms like vomiting, gastric
      remainder, diarrhoea, abdominal distension or severe presentation like
      necrotizing enterocolitis. and measures implemented for terminating the outbreak.
      In conclusion, our study analyses the viral origins of nosocomial infections in
      NICU and underline that the role of viral agents in neonatal nosocomial
      infections needs to be further investigated even in diseases traditionally
      considered of bacterial origin like necrotizing enterocolitis.

PMID- 21877998
TI  - Failure of oral DHEA treatment to increase local salivary androgen outputs of
      female patients with Sjogren's syndrome.
AB  - OBJECTIVES: Sjogren's syndrome (SS) is a female-dominant autoimmune disease
      characterized by androgen depletion and defective dehydroepiandrosterone (DHEA)
      processing enzymatic machinery in the salivary glands. We hypothesized that,
      because of these local failures, DHEA replacement therapy would be unable to
      improve the local androgen deficiency in SS salivary glands. METHODS: DHEA
      deficient female SS patients (n = 12) were treated with placebo for 4 months
      followed by DHEA 50 mg q.d. for 4 months. Serum and saliva, collected in the
      morning before the trial and after both periods, were analysed for pro-hormones,
      androgens, and androgen metabolite using an enzyme-linked immunosorbent assay
      (ELISA). RESULTS: DHEA treatment increased serum DHEA-sulfate from 1.3 +/- 0.1 to
      6.4 +/- 1.3 uM (p = 0.005), DHEA from 16.5 +/- 2.8 to 34.8 +/- 8.2 nM (p =
      0.012), androstenedione from 3.1 +/- 0.3 to 17.2 +/- 1.9 nM (p = 0.002), free
      testosterone from 2.2 +/- 0.1 to 7.7 +/- 1.1 pM (p = 0.002), DHT from 275.5 +/-
      24.4 to 834.6 +/- 122.8 pM (p = 0.002) and 3-alpha-diol-G from 3.8 +/- 0.6 to
      13.6 +/- 2.0 nM (p = 0.001). However, only salivary DHEA and DHT outputs
      increased significantly and 25% of the patients showed no increases, except for
      DHEA itself. Outputs of active androgens (T, DHT) and 3-alpha-diol-G metabolite
      correlated with salivation. CONCLUSIONS: The local androgen deficiency in SS
      salivary glands is not only caused by low serum DHEA(-S) because restoration of
      systemic androgen levels by DHEA treatment did not correct local androgen
      depletion. This could be explained by low or no capacity of DHEA-substituted
      patients to convert the pro-steroid to active androgen metabolites. Such
      intracrine failures affect women in particular, who must produce their salivary T
      and DHT locally from DHEA.

PMID- 21878000
TI  - Balancing efficacy and tolerability of prostaglandin analogues and prostaglandin
      timolol fixed combinations in primary open-angle glaucoma.
AB  - BACKGROUND: Lowering intraocular pressure (IOP) is currently the only therapeutic
      approach that preserves visual function in primary open-angle glaucoma. In making
      treatment decisions for first- and second-line therapy, the clinician needs to
      provide an appropriate balance of efficacy and tolerability. Prostaglandin
      analogues (PGAs) are frequently used as first-line monotherapy, because of their
      efficacy and low risk of systemic side effects. Similarly, PGA-based fixed
      combinations are frequently used in patients who progress or fail to achieve the
      target IOP. SCOPE: We have reviewed the literature on the management of primary
      open-angle glaucoma with PGAs, both as monotherapies and in fixed combinations.
      FINDINGS: In the clinical trial and meta-analysis data identified, bimatoprost
      0.03% seems to be associated with a greater overall ability to lower IOP compared
      with latanoprost, travoprost or tafluprost, at the cost of a slightly higher
      incidence of conjunctival hyperaemia. Studies indicate that patients' adherence
      to treatment is generally better with PGAs than with many other monotherapies. In
      patients requiring more than one IOP-lowering agent, fixed combination treatments
      may provide improved adherence and tolerability benefits compared with
      concomitant use of individual treatments. Bimatoprost/timolol fixed combination
      appears to be slightly more efficacious than latanoprost/timolol or
      travoprost/timolol, and tolerability differences between the fixed combinations
      appear to be slight, probably because the addition of timolol to the PGA
      component lessens the associated hyperaemia. Surveys on EU physician attitudes
      appear largely in line with these clinical data. CONCLUSION: An appropriate
      balance between efficacy and tolerability ensures optimum IOP lowering and
      reduces the risk of non-adherence. PGAs largely fulfil this need as monotherapies
      and as components of combinations.

PMID- 21878001
TI  - Chemical composition and insecticidal activity of the essential oil of Amethystea
      caerulea L.
AB  - The essential oil of the aerial parts of Amethystea caerulea L. was obtained from
      steam distillation and investigated by GC and GC-MS. The main components of the
      essential oil were morrilol (25.1%), 4-vinylguaiacol (14.3%) and acetoanisole
      (14.3%), followed by linalool (6.6%), eugenol (5.8%) and alpha-caryophyllene
      (5.2%). The essential oil showed pronounced contact toxicity against Drosophila
      melanogaster L. and maize weevil, Sitophilus zeamais (Motsch.), with LD(50)
      values of 5.18 and 50.45 ug per adult, respectively. The essential oil also
      possessed strong fumigant toxicity against the maize weevils with an LC(50) value
      of 25.39 ug mL(-1).

PMID- 21878003
TI  - Isolation and X-ray crystal structure of a securinega-type alkaloid from
      Phyllanthus niruri Linn.
AB  - A securinega-type alkaloid epibubbialine was isolated from Phyllanthus niruri
      Linn. Its structure was established by spectroscopic methods and X-ray single
      crystal diffraction analysis. Its crystal structure is reported herein for the
      first time.

PMID- 21878002
TI  - A physiology-based inverse dynamic analysis of human gait using sequential convex
      programming: a comparative study.
AB  - This paper presents an enhanced version of the previously proposed physiological
      inverse approach (PIA) to calculate musculotendon (MT) forces and evaluates the
      proposed methodology in a comparative study. PIA combines an inverse dynamic
      analysis with an optimisation approach that imposes muscle physiology and
      optimises performance over the entire motion. To solve the resulting large-scale,
      nonlinear optimisation problem, we neglected muscle fibre contraction speed and
      an approximate quadratic optimisation problem (PIA-QP) was formulated.
      Conversely, the enhanced version of PIA proposed in this paper takes into account
      muscle fibre contraction speed. The optimisation problem is solved using a
      sequential convex programing procedure (PIA-SCP). The comparative study includes
      PIA-SCP, PIA-QP and two commonly used approaches from the literature: static
      optimisation (SO) and computed muscle control (CMC). SO and CMC make simplifying
      assumptions to limit the computational time. Both methods minimise an
      instantaneous performance criterion. Furthermore, SO does not impose muscle
      physiology. All methods are applied to a gait cycle of six control subjects. The
      relative root mean square error averaged over all subjects, epsilon(RMS), between
      the joint torques simulated from the optimised activations and the joint torques
      obtained from the inverse dynamic analysis was about twice as large for SO
      (epsilon(RMS) = 86) as compared with CMC (epsilon(RMS) = 39) and PIA-SCP
      (epsilon(RMS) = 50). epsilon(RMS) was at least twice as large for PIA-QP
      (epsilon(RMS) = 197) than for all other methods. As compared with CMC, muscle
      activation patterns predicted by PIA-SCP better agree with experimental
      electromyography (EMG). This study shows that imposing muscle physiology as well
      as globally optimising performance is important to accurately calculate MT forces
      underlying gait.

PMID- 21878004
TI  - Identification of volatile organic compounds in flowers of Astragalus lagopoides.
AB  - Composition of volatile organic compounds (VOCs) in flowers of Astragalus
      lagopoides was studied using a hydrodistillation extraction procedure coupled
      with gas chromatography-mass spectrometry. The analyses allowed the
      identification of a number of 25 compounds, among which the presence of several
      bioactive aromatic derivatives such as guaiacol, eugenol, linalool, alpha- and 4
      terpineol as well as nerol was attention-grabbing. Moreover, some other compounds
      like cyclohexane, 2-bromoethyl with repellent function also appeared to be
      present in the flower. As a result, the floral VOCs profile of A. lagopoides
      might reflect an adaptation to attract specialised pollinator insects. These
      findings provide important information for advances in understanding the
      ecological and evolutionary perspectives of pollination biology of the giant
      genus Astragalus.

PMID- 21878005
TI  - Effects of Danggui Buxue Tang, a traditional Chinese herbal decoction, on high
      glucose-induced proliferation and expression of extracellular matrix proteins in
      glomerular mesangial cells.
AB  - Diabetic nephropathy (DN) is the leading cause of end-stage failure of the
      kidney, but the efficacy of currently available strategies for the prevention of
      DN remains unsatisfactory. In this study, we investigated the effects of Danggui
      Buxue Tang (DBT), a Chinese herbal decoction prepared from Radix Astragali (RA)
      and Radix Angelicae sinensis (RAS), on high glucose-induced proliferation and
      expression of laminin, type IV collagen (collagen IV) and fibronectin in
      glomerular mesangial cells (GMCs). The cell proliferation was determined by MTT
      assay, and the expression of collagen IV, laminin and fibronectin in GMCs was
      detected by ELISA assay. It was shown that high glucose clearly induced the
      proliferation of GMCs and increased the release of collagen IV, laminin and
      fibronectin. Treatment with RA, RAS and DBT inhibited cell proliferation and the
      expression of collagen IV, laminin and fibronectin induced by high glucose, with
      DBT, especially at the highest concentration (DBT20), exhibiting a stronger
      effect than RA and RAS alone. Thus, it is concluded that DBT inhibits increased
      cell proliferation and the expression of major extracellular matrix proteins that
      are induced by high glucose, indicating its value for prophylaxis and therapy of
      DN at the early stages.

PMID- 21878006
TI  - 'It is time for Indigenous Australians to be recognised in the document that
      governs Australia. Constitutional acknowledgement of Indigenous people is long
      overdue'.

PMID- 21878007
TI  - Action research informing the development of a conceptual model of care and
      service delivery to populations of interest in rural and remote communities.
AB  - OBJECTIVES: This paper aims to identify and respond to workplace stress and
      related issues in a rural community mental health team. METHOD: Action research
      (AR) underpinned this study and facilitated change in practice through four
      distinctive completed AR cycles with data analysis proceeding alongside data
      collection. Theories were articulated and explored and resulted in the
      development of a new model of praxis. CONCLUSIONS: A new model of praxis was
      developed which should contribute to both positive patient outcomes and improved
      staff occupational safety and wellness. Based on this, three clinical nursing
      tools were developed and implemented into practice.

PMID- 21878008
TI  - Can administrative data provide insights into the mental health of Indigenous
      Queenslanders?
AB  - INTRODUCTION: The Australian Government has provided $20 million to establish the
      Population Health Research Network (PHRN), with representation from all States
      and Territories to facilitate population health research through data linkage.
      Health LinQ is part of the Queensland node involving four Queensland
      universities, Queensland Health and the Australian e-Health Research Centre.
      METHOD: This paper reviews the potential for using administrative databases to
      study the mental health experience of Indigenous Queenslanders. Researchers can
      define cohorts for study within the administrative data or link them to their own
      data. Robust protocols preserve confidentiality so that researchers only receive
      anonymized data. Indigenous status can be defined either through place of
      residence or through the recording of Indigenous status in datasets such as the
      Queensland Hospital Admitted Patient Data Collection. RESULTS: Available data
      include hospital morbidity, mental health data and mortality. Indigenous status
      is correctly identified in about 89% of cases with variation by definition used.
      CONCLUSIONS: Administrative data provide researchers and decision makers with
      accessible, cost-effective information without the intrusion and cost of
      additional data collection. These techniques are especially useful in studying
      regional, rural and remote populations where access may be difficult.

PMID- 21878009
TI  - Integrating treatment for mental and physical disorders and substance misuse in
      Indigenous primary care settings.
AB  - OBJECTIVE: Australian Indigenous peoples in remote and rural settings continue to
      have limited access to treatment for mental illness. Comorbid disorders
      complicate presentations in primary care where Indigenous youths and perinatal
      women are at particular risk. Despite this high comorbidity there are few
      examples of successful models of integrated treatment. This paper outlines these
      challenges and provides recommendations for practice that derive from recent
      developments in the Northern Territory. CONCLUSIONS: There is a strong need to
      develop evidence for the effectiveness of integrated and culturally informed
      individual and service level interventions. We describe the Best practice in
      Early intervention Assessment and Treatment of depression and substance misuse
      study which seeks to address this need.

PMID- 21878010
TI  - Starting a perinatal and infant mental health service at Winnunga Nimmityjah.
AB  - OBJECTIVE: This paper briefly describes how the contexts of social and emotional
      wellbeing in Aboriginal and Torres Strait Islander communities impacts on
      perinatal and infant mental health. In response to these issues, a perinatal and
      infant mental health service was started through Winnunga Nimmityjah, a community
      controlled Aboriginal health service. The process of starting the clinic and some
      clinical themes are described.

PMID- 21878011
TI  - Anxiety in children: remote area sensitivities and considered changes in
      structuring a Cool Kids approach.
AB  - OBJECTIVE: To explore the feasibility of utilizing Cool Kids, a mainstream
      resource based on cognitive behavioural principles, to address acute and chronic
      anxiety with Aboriginal children in a remote setting. RESULTS: Evidence from the
      literature suggests some symptomatic differences and learning challenges which
      demand consideration prior to implementation in this population. In particular,
      cultural sensitivities in many areas need to be respected, as does the sense of
      interconnectedness in terms of self and thinking. CONCLUSIONS: Given sufficient
      knowledge, appropriate cultural protocol, and concentration on engagement it
      should be possible to use an adapted Cool Kids program to decrease the high
      levels of anxiety in a remote Indigenous population. Being aware of the
      differences in western and Indigenous thinking and learning will help direct
      adaptation.

PMID- 21878012
TI  - Becoming empowered: a grounded theory study of Aboriginal women's agency.
AB  - OBJECTIVE: The study aim was to identify the process underlying the performance
      of agency for urban-dwelling Aboriginal women in contemporary Australian society
      with a view to promoting social change for Aboriginal people. METHOD: Grounded
      theory methods were used in the conduct of 20 life history narrative interviews
      with Aboriginal women from across fourteen different language groups. RESULTS:
      Analysis identified a specific ecological model of Aboriginal women's
      empowerment, defined as "becoming empowered". "Performing Aboriginality" was
      identified as the core category and encompassed the women's concern for carving
      out a fulfilling life and carrying out their perceived responsibilities as
      Aboriginal women. CONCLUSIONS: While confirming much of the extant literature on
      empowerment, the analysis also offered unique contributions--a spiritual
      sensibility, cultural competence and an ethics of care and morality. This sheds
      new light on the creative ways in which Aboriginal women "disrupt" discourses and
      create alternate modes of existence. The findings have implications for improving
      quality of life for Aboriginal people by informing the practical development and
      delivery of social and health policies and programs.

PMID- 21878013
TI  - Enterprising social wellbeing: social entrepreneurial and strengths based
      approaches to mental health and wellbeing in "remote" Indigenous community
      contexts.
AB  - OBJECTIVE: Social enterprises are market-based activities that provide social
      benefits through the direct engagement of people in productive activities.
      Participation in social enterprise development brings psychosocial wellbeing
      benefits, by strengthening family networks, enhancing trust, increasing self
      reliance and social esteem and promoting cultural safety. Our objective is to
      explore how social enterprise activities can meet community needs and foster self
      sustainability while generating profits for redistribution as social investment
      into other ventures that aid social functioning and emotional well-being.
      CONCLUSIONS: Social entrepreneurship enhances both interdependence and
      independence. Concomitant mental health and social wellbeing dividends accrue
      overtime to communities engaged in self-determined enterprise activities. Social
      entrepreneurship builds social capital that supports social wellbeing. Strengths
      based approaches to social entrepreneurship can assuage disempowering effects of
      the "welfare economy" through shifting the focus onto productive activities
      generated on people's own terms.

PMID- 21878014
TI  - Hip hopping the gap--performing arts approaches to sexual health disadvantage in
      young people in remote settings.
AB  - OBJECTIVE: Closing the gap in Indigenous health and wellbeing in remote settings
      in the Torres Strait and Northern Peninsula Area of Far North Queensland (FNQ)
      includes addressing a well-documented sexual health disadvantage among young
      people. Community mobilization around the underlying risk factors influencing
      sexual health is required. METHOD: Performing-arts-based workshops were conducted
      in schools and after-school venues in four remote Aboriginal and Torres Strait
      islander locations in FNQ in early 2010, to initiate consciousness-raising around
      the real dimensions of youth sexual health risk. Specific objectives included
      strengthening operational partnerships at school-level and developing ongoing
      consultative processes in each location for sexual health reference group
      development. RESULTS: Results include a significantly strengthened productive
      partnership with primary and high schools in each location and sixteen production
      ready hip hop songs exploring a range of physical, emotional and sexual health
      themes authored by the students and recorded on site. Additional outcomes
      included the willingness of community councils and civil society organizations to
      support local sexual health reference group activity. CONCLUSIONS: This
      initiative, the Indigenous Hip Hop Project, although accompanied by opportunity
      costs including alternative, more core business uses of staff time and program
      budget, has demonstrated the power of tapping the creative energy of young people
      at risk and the potential for mobilizing communities to activism around sexual
      health disadvantage.

PMID- 21878015
TI  - How can country, spirituality, music and arts contribute to Indigenous mental
      health and wellbeing?
AB  - OBJECTIVE: Mental health and social and emotional wellbeing (SEWB) have been
      linked as outcomes of attachment to country, spirituality, and engagement in
      music and arts, particularly for Indigenous Australians. It is not clear how this
      occurs, even though the links seem substantial. METHOD: We explore how mental
      health and SEWB may be linked to attachment to country, spirituality, and
      engagement in music and arts by reviewing literature and presenting examples from
      our research with Indigenous communities. Rather than abstracting, our goal is to
      describe specific examples encompassing the rich contextual details needed to
      understand the factors contributing to mental health and SEWB. RESULTS: While
      engagement in music is often seen as benefiting mental health because thoughts
      and feelings can be expressed in less public ways, it can also lead to employment
      and access to economic and social resources. Attachment to country also shows a
      plethora of positive outcomes which can contribute to mental health and SEWB even
      when not explicitly aimed at doing so, such as reducing conflictual situations.
      CONCLUSIONS: We conclude that more detailed, contextual research is required to
      fully explore the links between creative enterprises and mental health and SEWB
      outcomes.

PMID- 21878016
TI  - Creating Futures 2010: Harnessing creativity and social enterprise for social and
      emotional wellbeing: human rights considerations.

PMID- 21878017
TI  - An art-based healing process: The Aurukun creative livelihoods project at the Wik
      and Kugu Arts and Craft Centre.
AB  - OBJECTIVES: This paper describes the challenges in implementing an innovative
      arts-based mental health project in a remote Indigenous community. METHOD: The
      author (the Art Centre Manager) presents a personal narrative of the development
      of the Aurukun Creative Livelihoods project. RESULTS: A partnership between an
      existing arts and mental health project (Creative Recovery) and the Wik and Kugu
      Arts and Craft Centre is described. This collaboration aims to enhance the
      emotional and social wellbeing of vulnerable Aboriginal people in a remote
      Indigenous community in Cape York - Aurukun.

PMID- 21878018
TI  - Work in progress: Creative Recovery to creative livelihoods.
AB  - OBJECTIVE: The purpose of this study was to provide an update on the performative
      outcomes of the Creative Recovery project, an innovative community based Arts in
      Health initiative, since the initial launch in Lockhart River 2008, expansion to
      Aurukun in 2009, and Mornington Island in 2010. RESULTS: With works from those
      three communities, the exhibition Work In Progress was launched during the
      Creating Futures Conference 2010. Selections from that exhibition are presented
      here. CONCLUSIONS: The Arts in Health model is both a culturally appropriate and
      sustainable model for the meaningful engagement of Indigenous people living in
      remote communities experiencing mental health problems. These types of projects
      offer unique opportunities for social enterprise, utilizing creativity as the
      tool for social inclusion. It has the potential to provide a niche economic
      opportunity which builds on the notion of recovery as incorporating meaningful
      livelihoods.

PMID- 21878019
TI  - The primary determinants of Indigenous household information and communication
      technology adoption: remote, rural and urban.
AB  - OBJECTIVE: This paper examines the factors affecting adoption of information and
      communication technologies (computers and the Internet) in Australian Indigenous
      households across three Indigenous communities, remote, rural and urban. Drawing
      on the sociological notion of structure and agency it is argued that being
      engaged in external fields influences Indigenous household ICT adoption. This
      paper develops a conceptual schema by drawing on Bourdieu's theory of habitus to
      explain the low uptake of ICTs in Indigenous households across Australia.
      CONCLUSIONS: Evidence suggests that there is more commonality across diverse
      communities than differences.

PMID- 21878020
TI  - Performative evaluation and social return on investment: potential in innovative
      health promotion interventions.
AB  - OBJECTIVE: The purpose of this study was to describe an approach to evaluation of
      a project involving complex health behaviours that incorporates collateral social
      outcomes. METHOD: Evaluation challenges and responses for an innovative
      information and communication technologies for development (ICT4D) initiative
      (HITnet) operating in remote Indigenous Australia are presented. CONCLUSIONS:
      Innovation in evaluation must match innovation in project design and application.
      Two methodologies--performative research, and social return on investment--as
      proposed for a HITnet, sexual health promotion project, are considered.

PMID- 21878021
TI  - Reaching the hard-to-reach: how information communication technologies can reach
      young people at greater risk of mental health difficulties.
AB  - OBJECTIVE: Inspire and partners have built an evidence base examining the role
      technology can play in supporting the mental health and wellbeing of young people
      at increased risk of developing mental health difficulties. This paper explores
      these findings collectively and considers how to best use information
      communication technologies (ICT) to meet the mental health needs of diverse young
      people aged 14-25. CONCLUSIONS: ICT offers relevant and innovative strategies for
      young people at increased risk of developing mental health difficulties. Whilst
      many young people experience social isolation and stigma, the manifestation of
      these issues and the strategies required to address them vary. ICT-based programs
      will benefit from identifying which protective factors can be most positively
      influenced through the unique properties of ICT, amongst whom and how. Challenges
      to ICT-based health services include inadequate access and training, lower
      literacy levels and the need for specialized technologies for people with
      disabilities.

PMID- 21878022
TI  - Enabling all young Australians to grow up safe, happy, healthy and resilient: a
      Collaboration for Young People, Technology and Wellbeing.
AB  - OBJECTIVE: This paper describes a framework for a multi-disciplinary
      collaboration to investigate the role of technology for improving young
      Australians' mental health and wellbeing. RESULTS: The poor mental health of
      young Australians poses a significant challenge to Australia's future. Half of
      all Australians will experience a mental health difficulty in their lifetime and
      75% of mental illness has its onset before age 25. Cross-sectoral collaboration
      is critical for meeting this challenge. In order to establish a world-first multi
      partner collaboration, leading researchers and institutes, commercial, non-profit
      and end-user organization and young people were identified and invited to
      participate. Together we have developed an international research framework that
      explores the role of technologies in young people's lives, their potential and
      how this can be harnessed to address challenges facing young people. This
      research framework will: (i) conduct empirical research that tests the utility of
      technology across mental health promotion, prevention, early intervention and
      treatment and, (ii) translate existing and new knowledge into products and
      services that help create a generation of safe, happy, healthy and resilient
      young people. Research undertaken by the Collaboration will be the most
      comprehensive investigation of technologies' potential to improve the wellbeing
      of young people ever conducted, leading to significant benefits for Australian
      young people and their mental health.

PMID- 21878023
TI  - How the creative spirit saved me from a fate worse than hospitalization.
AB  - Ross is a mental health patient representative based in Cairns and has been a
      member of the Cairns CAG for the past eight years. He has played a significant
      role in the development of consumer participation in Cairns and at a state level.
      Ross has sat on a range of committees as a consumer representative and has worked
      as an accreditor with the Institute of Healthy Communities Australia. Currently
      he sits on the management committee of the Queensland Voice for Mental Health.
      Ross was a founding member of the Irukandji Pens writers group, based at the
      Cairns Mental Health Resource Service.

PMID- 21878025
TI  - Creating an open mind.
AB  - Duncan Monaghan is 33 years old and in his second year of an Arts degree in
      Creative Writing. He is a published poet and is currently producing a music CD.
      Duncan has a history of bipolar disorder which was diagnosed when he was
      nineteen: "It worried me at first a lot. It played on my mind constantly. I felt
      different from everybody else--I did not understand what was happening to me."
      Drawing on his life experiences, Duncan has been enhancing his recovery through
      creativity--in poetry, lyrics, music and story. "Life for me was a constant
      battle of relying on medication and appointments with my case manager...until I
      realized I could combine my recovery with my passions as a tool to use as an
      outlet to many of the "mind traps" I so often found hindering my own recovery."
      Duncan is Aboriginal and has experience of the mental health systems in most
      states and territories and now lives in Brisbane. This is a shortened version of
      his presentation at Creating Futures 2010.

PMID- 21878024
TI  - Poetry through soul.
AB  - Trevor Clark usually works as a bulk fuel truck driver. He has a passion for
      poetry, writing and guitar playing which he uses as a sounding board for
      reflective learning and development. He also believes that supportive family and
      friends are critical to maintaining his well-being. Sustaining recovery is a
      reality Trevor deals with every day and believes patients who embrace their
      condition fully can direct their recovery and maintain positive mental health for
      themselves and those involved in their lives. Currently, Trevor is working on his
      first novel while he recovers from physical injuries incurred on his quest for
      autonomy and place. Managing his mental health is of paramount importance to
      Trevor and even though this may be trying at times, he lives and works happily
      with his condition.

PMID- 21878026
TI  - Arc of opportunity.
AB  - Born in Port Moresby, Papua New Guinea, the author had a 20 year career in
      diplomacy, political affairs, and development policy analysis at the Pacific
      Islands Forum, the United Nations in New York; the Prime Minister's Department in
      Papua New Guinea (PNG) and in the Foreign Ministry of PNG. He has also been
      involved in theatre for over a decade in PNG, and participated in a three-month
      program at the Eugene O'Neill Theatre Center in Connecticut, USA. He is currently
      the Business Development Manager at the Torres Strait Regional Authority
      (Commonwealth) on Thursday Island. Since 1975 the Australian government's
      overseas development policy has supported various sectoral programs in its
      neighbouring countries, in particular Papua New Guinea and the Solomon Islands.
      The "creative" field has not been prominent in this strategy. While natural
      resources and the sports sectors have gained much greater attention, in terms of
      being viable international commercial enterprises, the arts, have remained
      stagnant. In this paper the need for joint programs genuinely supporting
      "wellbeing" and promoting social enterprise throughout the "arc of opportunity"
      is described to harness Melanesian creativity to compete successfully in world
      markets, starting with penetration of the largest economy at its door-step:
      Australia.

PMID- 21878027
TI  - Indigenous mental health 2035: future takers, future makers and transformational
      potential.
AB  - OBJECTIVE: The aims were to review progress in Indigenous mental health over the
      past 25 years and to identify possible directions for the next 25 years. METHOD:
      Maori involvement in health and health care was used to illustrate key Indigenous
      developments since 1984. Challenges in the decades ahead were discussed in the
      context of demographic transitions, life course epidemiology, global trends,
      technological innovations and health leadership. RESULTS: Progress was measured
      by a range of indicators including Maori-referenced life expectancy, Maori
      agendas for health, strengthened cultural identity, the dissemination of health
      knowledge, and Maori participation in the health sector. In contrast to being
      ready to respond to change (future takers), active planning for the future
      (future makers) was seen as a better way of achieving Indigenous aspirations. One
      option for health advancement currently being developed in New Zealand involved
      an integrated approach premised on intersectoral delivery and a focus on
      families. CONCLUSIONS: Indigenous health will be advanced by dedicated approaches
      to family wellbeing that avoid fragmentation, focus on positive strengths, and
      lead to positive outcomes for family members and the family as a whole.

PMID- 21878028
TI  - Adaptability and sustainability of an Indigenous Australian family wellbeing
      initiative in the context of Papua New Guinea: a follow up.
AB  - OBJECTIVE: This paper describes the follow-up phase of a pilot collaborative
      initiative between the University of Papua New Guinea and James Cook University
      aimed at determining the relevance of an Indigenous Australian Family Wellbeing
      (FWB) empowerment program in the context of Papua New Guinea (PNG). It describes
      opportunities and challenges involved in adapting and sustaining the FWB approach
      to the PNG context. Two evaluation questionnaires were administered to 60 course
      participants. CONCLUSIONS: Findings revealed that the course was relevant,
      adaptable and could readily be integrated with other health programs. In the
      context of PNG's target to meet its United Nations Millennium Development Goals
      by 2015, the Family Wellbeing approach offers an innovative approach to enhance
      existing health and community development initiatives.

PMID- 21878029
TI  - Health consequences of disparity: the US Affiliated Pacific Islands.
AB  - Health disparities and the social determinants of health are often discussed, but
      their relationship to political forces, the integrity of cultures, social and
      environmental change, and mental health outcomes are not well understood.
      Specifically the US Affiliated Pacific Islands Jurisdictions (USPAIJ) is an area
      of profound isolation and deprivation with a unique sociocultural history. This
      article provides an overview of health disparities in the US Affiliated Pacific
      in the context of the environment, and international and state policies. The
      article explores how the political, economic, social, and environmental context
      of the USAPIJ shapes health status and provides a "social determinants of health"
      model for health improvement for the people of the region.

PMID- 21878030
TI  - Staff management and capacity building under conditions of insecurity: lessons
      from developing mental health service and research programs in post-conflict
      Timor-Leste.
AB  - OBJECTIVE: The task of staff capacity building is particularly important, albeit
      challenging, in low and middle income countries emerging from prolonged periods
      of persecution and conflict. Mental health professionals engaged in development
      and research projects are acutely aware of the impact of past and current
      conditions including trauma exposure, insecurity, and poverty on the capacity of
      local workers to acquire and apply skills. In this article we reflect on these
      challenges by drawing on our experience spanning 10 years of mental health work
      and capacity building in Timor-Leste. CONCLUSIONS: It is important to be
      proactive in identifying the needs and career objectives of workers early in any
      development initiative so that an effective program of capacity building can be
      initiated. Careful consideration needs to be given to ensure a compassionate and
      considered response to the psychosocial needs of staff, one that takes into
      account the impact of past trauma, ongoing insecurity and socioeconomic
      conditions on the capacity of workers to function effectively.

PMID- 21878031
TI  - "The family is the clinic, the community is the hospital": community mental
      health in Timor-Leste.
AB  - OBJECTIVE: This paper describes the history and recent development of mental
      health services in Timor-Leste, a small developing country recovering from
      conflict. Challenges to effective service delivery are discussed as well as plans
      for future development. CONCLUSIONS: Timor-Leste's mental health service began
      just over a decade ago. Unlike many other low and middle income countries where
      hospital-based services predominate, the mental health model in Timor-Leste is
      entirely community based. However, challenges to effective mental health care
      delivery are similar to most developing countries and include a lack of
      sufficient financial resources, human resources, and mental health
      infrastructure. Addressing these issues successfully requires political will, a
      greater prioritization of mental health services, close coordination between
      stakeholders, as well as developments in the area of education, training and
      infrastructure. Greater understanding and education about the links between
      mental and physical health would benefit the overall health of the population,
      and integration of these respective policies may prove a successful method of
      more equitably redistributing finances and resources.

PMID- 21878032
TI  - Intentional teams in rural health care: a preliminary report.
AB  - OBJECTIVE: This paper reports on how private practitioners were engaged in a
      rural community in an intentional team to provide a comprehensive lifestyle
      program for "hard to treat" patients with physical and mental health problems.
      METHODS: A field trial of a 12-week program for patients with depression or
      anxiety plus other chronic disease was delivered by a team of allied health
      practitioners. RESULTS: Significant improvements in mental health as measured by
      DASS and SF36 were achieved. CONCLUSIONS: Utilizing community resources
      effectively can lessen the burden on other aspects of the health care system.

PMID- 21878033
TI  - Antibacterial activity of three medicinal Thai plants against Campylobacter
      jejuni and other foodborne pathogens.
AB  - Leaves of Adenanthera pavonina, Moringa oleifera and Annona squamosa are used in
      traditional Thai medicine to treat dysentery and other diseases. This study
      investigated the antibacterial activity of these plants against six species of
      foodborne pathogen. Methods and solvents employed to extract active constituents
      were optimised using the disc diffusion assay. Phytochemical analysis of the
      optimised extracts was performed by thin layer chromatography (TLC). Minimum
      inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs)
      were determined by broth microdilution. A. pavonina contained flavonoids,
      terpines and tannins, and was the most active extract against Campylobacter
      jejuni, inhibiting growth at 62.5-125 ug mL(-1). The A. squamosa extract
      contained flavonoids, terpines, tannins and alkaloids, and had the broadest
      spectrum of antibacterial activity, inhibiting Bacillus cereus, Listeria
      monocytogenes, Staphylococcus aureus and C. jejuni between 62.5 and 500 ug mL(
      1). MBCs were 2- to 4-fold higher than MICs against C. jejuni and B. cereus,
      suggesting the extracts are bactericidal against these species. Negligible
      activity was detected from M. oleifera. The data presented here show that A.
      pavonina and A. squamosa could potentially be used in modern applications aimed
      at the treatment or prevention of foodborne diseases.

PMID- 21878034
TI  - The impact of motivational interviewing on resistance in cognitive behavioural
      therapy for generalized anxiety disorder.
AB  - The present study simultaneously examined observed resistance and homework
      compliance in Cognitive Behavioural Therapy (CBT) between those with severe
      generalized anxiety disorder who did (n =18) and did not (n =17) receive
      Motivational Interviewing (MI) prior to CBT. Large effects for reduced resistance
      early in CBT were observed in the MI pretreatment group relative to the no
      pretreatment group. Moreover, receiving four sessions of MI was associated with
      significantly lower levels of resistance, compared to receiving four sessions of
      CBTalone. Using path analysis, resistance, but not homework compliance, was found
      to strongly and directly mediate the relationship between treatment group and
      worry reduction. Findings suggest that MI improves treatment outcomes when added
      to CBT for generalized anxiety by reducing client resistance to, and increasing
      client engagement with treatment.

PMID- 21878035
TI  - The prognostic role of evoked potentials in neonatal hypoxic-ischemic insult.
AB  - Neonatal encephalopathy is a significant cause of infant mortality and morbidity
      with risk of neurological sequelae in the survivors of neonates admitted to
      Neonatal (N) Intensive Care Unit (ICU). The EEG and Evoked Potentials (EPs) are
      very informative in the ICU. In particular, it is known that the SomatoSensory
      (SS) EPs are the best single indicator of early prognosis in adults and children
      patients with traumatic and/or hypoxic-ischemic coma compared to the Glasgow Coma
      Scale (GCS) and CTscan. Most paediatric studies excluded newborns in an attempt
      to eliminate the age effects, because of the structural and functional immaturity
      of somatosensory system. In fact, newborns differ from adults and paediatric
      patients for many aspects: hypoxic-ischemic aetiology, SSEPs normative data,
      grading and predictive values, timing and techniques recording, clinical scales
      of evaluation. Recently a diagnostic and predictive role of early SSEPs has been
      established in perinatal hypoxic-ischemic. We reported a literature review of
      early diagnostic/prognostic role of SSEPs and our preliminary neurophysiological
      data of prospective study in mild or severe perinatal hypoxic-ischemic insult.

PMID- 21878036
TI  - Hot flushes in healthy aging men differ from those in men with prostate cancer
      and in menopausal women.
AB  - Calcitonin gene-related peptide (CGRP) seems to be involved in hot flushes in
      women and in castrated men. Therefore, we studied whether the plasma
      concentrations of CGRP changed during flushes in a group of healthy aging men.
      Twelve men (49-71 years) with no history of current or former prostate cancer or
      hormonal treatment reporting >= 20 flushes/week were investigated. Blood samples
      were drawn during and between flushes for analysis of CGRP and also androgen
      concentrations, that is, testosterone and bioavailable testosterone were
      analysed. Skin temperature and skin conductance were monitored. Thirty-five
      flushes were reported by 10 men. The plasma concentrations of CGRP did not
      increase during flushes. No significant change in skin temperature or conductance
      was found. CGRP is probably not involved in the mechanisms of flushes in healthy
      aging men. Therefore, flushes in aging healthy men seem to be different from
      flushes in men and women deprived of sex steroids where CGRP increases during
      flushes.

PMID- 21878037
TI  - Maternal preeclampsia is associated with an increased risk of retinopathy of
      prematurity.
AB  - OBJECTIVE: To determine the effect of maternal preeclampsia on development and
      severity of retinopathy of prematurity (ROP) in preterm infants. METHODS: This
      prospective study consisted of two groups: the study group, which is composed of
      preterm infants (<=32 weeks) born to a mother with preeclampsia, and the
      comparison group, which is composed of preterm infants (<=32 gestational age)
      born to normotensive mothers. We used the International Classification of
      Retinopathy of Prematurity Revisited for classifying ROP. The first eye
      examination was performed at postnatal age of 4 weeks. RESULTS: A total of 385
      infants were included in the study. ROP was diagnosed in 109 infants (28%). The
      incidence of ROP in infants born to preeclamptic mothers (40.5%) was
      significantly higher compared with those born to normotensive mothers (22.4%)
      (P<0.05). The number of infants with stage 1, 2, and 3 ROP was significantly
      higher in infants born to preeclamptic mothers compared with the control group
      (P<0.05). In multiple logistic regression model, preeclampsia was found to
      predict ROP (odds ratio 1.78, 95% confidence interval 0.66-1.90). CONCLUSION:
      Maternal preeclampsia was found to be associated with increased ROP development
      risk in premature infants. ROP was also more severe in infants born to pre
      eclamptic mothers. The role of maternal preeclampsia in the occurrence and
      severity of ROP remains to be elucidated.

PMID- 21878038
TI  - Can interventions have negative impacts? The importance of seeing the bigger
      picture.

PMID- 21878039
TI  - Myocardial fibrosis as a risk stratifier for sudden arrhythmic death.

PMID- 21878041
TI  - Selective and specific I(f) inhibition with ivabradine: new perspectives for the
      treatment of cardiovascular disease.
AB  - Heart rate is a major determinant of myocardial oxygen demand and supply, and
      increased heart rate adversely affects the pathophysiology of myocardial
      ischemia. High resting heart rate is a risk factor in cardiovascular disease. The
      development of the heart rate-lowering agent ivabradine showed that heart rate
      was also an important treatment target, notably in coronary artery disease and
      heart failure. Indeed, heart rate reduction with ivabradine, a selective and
      specific I(f) inhibitor, reduces myocardial oxygen demand, increases diastolic
      perfusion time and improves energetics in ischemic myocardium. Ivabradine
      protects the myocardium during ischemia, improves left ventricular function in
      heart failure and reduces remodeling following myocardial infarction. It improves
      prognosis in patients with coronary artery disease, left ventricular dysfunction
      and heart rate >=70 beats per minute, as well as in patients with heart failure
      and left ventricular dysfunction. Ivabradine is safe, well tolerated and can be
      used in combination with the main drugs for cardiovascular disease.

PMID- 21878043
TI  - TCTAP 2011: connecting East and West for interventional societies.
AB  - The Angioplasty Summit TCTAP is an international conference held annually at the
      end of April in Seoul, Korea that focuses on interventional cardiology. Over the
      past two decades, this meeting has played an integral part in the Asia-Pacific
      region on educating physicians and other healthcare professionals who are
      interested in this field. It has become a very useful opportunity for them to
      catch up with cutting-edge techniques, overviews and clinical investigations from
      all over the world.

PMID- 21878042
TI  - An overview of candesartan in clinical practice.
AB  - Hypertension is a major risk factor for coronary heart disease, stroke, heart
      failure and renal disease. The Joint National Committee on Prevention, Detection,
      Evaluation and Treatment of High Blood Pressure 7 defined hypertension as a blood
      pressure of more than 140/90 mmHg and recommended to initiate treatment with a
      two-drug combination for stage 2 hypertension (blood pressure of 160-179/100-109
      mmHg). The need for drug combinations is clear from a patient and physician
      perspective as they provide more effective blood pressure lowering, reduce pill
      burden, improve compliance and decrease hypertension-related morbidity and
      mortality. Angiotensin II receptor blocker therapy has been proven to be well
      tolerated and effective in the management of hypertension, chronic heart failure
      with left ventricular dysfunction and the prevention and progression of diabetic
      renal disease. Blockers of the renin-angiotensin system are an important
      component of antihypertensive combination therapy. Thiazide-type diuretics are
      usually added to increase the blood pressure lowering efficacy. Fixed drug-drug
      combinations of both principles, such as candesartan/hydrochlorothiazide, are
      highly effective in lowering blood pressure while providing improved compliance,
      a good tolerability and largely neutral metabolic profile. In this article, we
      review the literature for the role of candesartan-based therapy for hypertension,
      stroke, diabetes mellitus and heart failure.

PMID- 21878044
TI  - Why, when and how should hypertriglyceridemia be treated in the high-risk
      cardiovascular patient?
AB  - Recent epidemiology attests that hypertriglyceridemia may be a causal risk factor
      for cardiovascular disease (CVD). The specific atherogenicity of
      hypertriglyceridemia relates to the accumulation in plasma of triglyceride-rich
      lipoprotein remnants. Hypertriglyceridemia also drives a 'global' atherogenic
      dyslipidemic profile, which is frequent in high-risk cardiovascular patients,
      such as Type 2 diabetics. Elevated triglyceride in fasting or nonfasting blood
      samples should be a trigger for assessing atherogenic components of the lipid
      profile, particularly HDL-cholesterol, non-HDL-cholesterol and apoB. Residual
      risk of CVD remains high in statin-treated diabetic patients owing to persistent
      atherogenic dyslipidemia, which is not fully corrected by these agents nor by the
      addition of ezetimibe. Hypertriglyceridemia may then be targeted with niacin,
      fibrates or n-3 fatty acids, after correcting aggravating factors, especially
      obesity and hyperglycemia. Fibrates consistently decrease coronary events in
      dyslipidemic patients in outcome studies. New evidence supports adding
      fenofibrate to a statin in Type 2 diabetics with residual hypertriglyceridemia
      and low HDL-cholesterol; extrapolating from a recent meta-analysis, a 15%
      reduction in triglycerides could translate into a further 15% reduction in
      coronary events. Ongoing clinical trials may provide new evidence for adding
      niacin to a statin. The value of higher doses of n-3 fatty acids in reducing CVD
      risk remains to be demonstrated. The high triglyceride/low HDL nexus is an under
      recognized risk factor for CVD that merits more detailed clinical assessment and
      treatment, particularly in patients with Type 2 diabetes already receiving a
      statin.

PMID- 21878045
TI  - The future of platelet function testing to guide therapy in clopidogrel low and
      enhanced responders.
AB  - Dual oral antiplatelet therapy with aspirin and clopidogrel is the therapy of
      choice in patients with acute coronary syndromes and in patients undergoing
      coronary stent placement to lower the risk of thrombotic events. Responsiveness
      to aspirin and especially to clopidogrel is not uniform and is subject to
      considerable interindividual variability. Furthermore, there is a broad consensus
      that clopidogrel low response or so-called high on-treatment platelet reactivity
      is linked to the occurrence of ischemic events. On the other hand, evidence is
      accumulating that enhanced clopidogrel responders are at increased risk of
      bleeding. Newer antiplatelet drugs, such as prasugrel and ticagrelor, are more
      potent and produce more consistent inhibition of platelet aggregation via the
      P2Y(12) ADP platelet receptor. A variety of methods of platelet function testing
      are available for evaluating platelet inhibition in percutaneous coronary
      intervention-treated patients in order to help determine the individual risk for
      ischemic and bleeding complications. Although not yet routinely undertaken,
      platelet function testing offers the potential to tailor antiplatelet therapy for
      individual patients. Whether alteration of therapy based on platelet function
      testing improves patients' outcomes remains unclear and is currently under
      investigation. This article reviews the impact of antiplatelet drug
      responsiveness on clinical outcomes with a focus on P2Y(12) receptor inhibition
      as well as on current and future concepts for personalized antiplatelet
      strategies.

PMID- 21878046
TI  - Stem cells for cardiac repair in acute myocardial infarction.
AB  - Despite recent advances in medical therapy, reperfusion strategies, implantable
      cardioverter-defibrillators and cardiac assist devices, ischemic heart disease is
      a frequent cause of morbidity and mortality worldwide. Cell therapy has been
      introduced as a new treatment modality to regenerate lost cardiomyocytes. At
      present, several cell types seem to improve left ventricular function in animal
      models as well as in humans, but evidence for true generation of new myocardium
      is confined to the experimental models. In the clinical perspective, myocardial
      regeneration has been replaced by myocardial repair, as other mechanisms seem to
      be involved. Clinical studies on adult stem cells suggest, at best, moderate
      beneficial effects on surrogate end points, but some applications may qualify for
      evaluation in larger trials. Complete regeneration of the myocardium by cell
      therapy after a large myocardial infarction is still visionary, but pluripotent
      stem cells and tissue engineering are important tools to solve the puzzle.

PMID- 21878047
TI  - Myocardial regeneration in heart failure: integrated development of biological
      therapeutic approaches.
AB  - Heart failure currently constitutes one of the greatest health problems in the
      Western world. Its incidence, far from diminishing or even remaining stable, is
      actually still increasing in association with the aging of the population and its
      lifestyle. A better knowledge of physiopathological mechanisms has allowed for
      the development of new therapeutic focal points and lines of research.
      Nevertheless, its treatment is complex and encompasses a multidisciplinary
      approach. Patients in an advanced stage still have a very high mortality rate in
      spite of receiving optimum medical care. The development of new therapeutic
      techniques that afford a better prognosis has therefore been essential. Of these,
      and leaving aside surgical treatments, myocardial regeneration by means of
      cellular therapy, new concepts in tissue engineering and their results, and the
      applications of new advances in the field of immunomodulation have all recently
      experienced development. In this article, the aim is to bring the latest concepts
      in the physiopathology and humoral response of cardiac failure up to date as well
      as doing the same with the therapeutic approaches in this area.

PMID- 21878048
TI  - Treatment of persistent atrial fibrillation using phased radiofrequency ablation
      technology.
AB  - A novel ablation system consisting of a duty-cycled phased radiofrequency
      generator and multielectrode mapping and ablation catheters has been introduced
      to provide ablation therapy in patients with symptomatic atrial fibrillation
      (AF). Contiguous lesions may be created using anatomically designed ablation
      catheters maneuvered under fluoroscopic guidance without the use of a 3D
      electroanatomic mapping system. In addition to pulmonary vein isolation using a
      circular, decapolar ablation catheter, an ablation strategy targeting complex
      fractionated atrial electrograms can be performed using two supplemental
      multiarray catheters specifically designed for ablation at the left atrial septum
      and within the left atrial body. Procedural times for treating persistent AF
      using phased radiofrequency are reported as being between 2 and 2.5 h. Freedom
      from AF ranges between 33 and 75% after a single procedure, which is comparable
      to other conventional ablation approaches (utilizing electroanatomic mapping).
      Additional studies in larger patient numbers are needed to understand the long
      term maintenance of results and potential adverse effects of the technology.

PMID- 21878049
TI  - Catheter ablation of electrical storm.
AB  - Electrical storm (ES) is defined as the occurrence of >= three distinct episodes
      of ventricular arrhythmia (VA) in patients with implanted defibrillators within
      24 h. Whereas conventional strategies for acute rhythm stabilization may be
      effective in some patients the occurrence of ES impairs survival and predicts
      recurrent VA. Catheter ablation in the setting of ES is complex and involves
      decisive strategies for individualized ablation approaches adapted to the
      patient's cardiac abnormalities. Success rates have been documented to be between
      79 and 94% in larger studies and effective ablation improves survival and freedom
      from any VA. Ablation should be considered early in the treatment plan and
      availability may be improved by interhospital collaboration with highly
      experienced VA intervention centers.

PMID- 21878050
TI  - Aging is a primary risk factor for cardiac arrhythmias: disruption of
      intracellular Ca2+ regulation as a key suspect.
AB  - Aging is an inevitable time-dependent progression associated with a functional
      decline of the cardiovascular system even in 'healthy' individuals. Age
      positively correlates with an increasing risk of cardiac problems including
      arrhythmias. Not only the prevalence but also the severity of arrhythmias
      escalates with age. The reasons for this are multifactorial but dysregulation of
      intracellular calcium within the heart is likely to play a key role in initiating
      and perpetuating these life-threatening events. We now know that several aspects
      of cardiac calcium regulation significantly change with advancing age - changes
      that could produce electrical instability. Further development of knowledge of
      the mechanisms underlying these changes will allow us to reduce what currently is
      an inevitable increase in the incidence of arrhythmias in the elderly.

PMID- 21878051
TI  - Treatment of lipid disorders in obesity.
AB  - Obesity is the most common cause of secondary hyperlipidemia. Atherogenic
      dyslipidemia refers to elevated triglycerides, low HDL-cholesterol and small
      dense LDL associated with visceral obesity and metabolic syndrome. Obesity may
      also be associated with isolated low HDL-cholesterol or high triglycerides and
      postprandial hyperlipidemia. While some obese patients have high LDL cholesterol
      concentrations, obesity has a more pronounced effect on other atherogenic lipids
      and lipoproteins. Obesity may aggravate familial lipid disorders. Lipid disorders
      in obesity are responsive to weight loss, pharmacotherapy and weight loss
      surgery. Statins are the lipid-lowering drug of choice, together with lifestyle
      change. Hard clinical end point data to support combinations of statins with
      other drugs is lacking. After weight loss surgery, the absolute risk of
      cardiovascular disease should be reassessed, but tools to facilitate risk
      assessment need to be developed.

PMID- 21878052
TI  - Atrial fibrillation: an epidemic in the elderly.
AB  - Atrial fibrillation is the most common cardiac arrhythmia that increases in
      prevalence with age. As the general population grows older, general practitioners
      will more frequently see this disease in their clinic population. In order to
      most effectively treat these patients, physicians need to understand key issues,
      including the use of rhythm control versus ventricular rate control and how to
      reduce the risk of ischemic stroke. This article will review recent advancements
      in the understanding of the pathophysiology, management, stroke risk
      stratification and prevention of thromboembolic complications in atrial
      fibrillation.

PMID- 21878053
TI  - A guide to the treatment of depression in women by estrogens.
AB  - Premenstrual depression, postnatal depression and climacteric depression are
      related to changes in ovarian hormone levels and can be effectively treated by
      hormones. It is unfortunate that psychiatrists have not accepted this form of
      treatment and this paper is an attempt to simplify this treatment, which should
      include transdermal estrogens, possibly testosterone and, if the woman has a
      uterus, also progestogen. A balance is often necessary between these three
      hormones. Transdermal estrogens in the appropriate dose will suppress ovulation
      and suppress the cyclical hormonal changes that produce premenstrual depression.
      Estrogens also have a mood-enhancing effect in postnatal depression and the
      depression in the transitional phase of the menopause. It is possible to add
      transdermal testosterone which will improve mood, energy and libido. The problem
      is the progestogen as these women are often progestogen-intolerant. Progestogen
      should be used in the lowest dose and for the shortest duration necessary to
      prevent endometrial hyperplasia or the return of premenstrual syndrome-type
      symptoms if the women are progestogen-intolerant. The use of estrogens for
      depression in these women does not exclude the use of antidepressants. Hormone
      responsive depression cannot be diagnosed by measuring hormone levels but can
      only be diagnosed by a careful history relating depression to the menstrual
      cycle, pregnancies and the perimenopausal years. These appropriate questions
      should prevent the endocrine condition of premenstrual depression being
      misdiagnosed as bipolar disorder and the woman given inappropriate treatment.

PMID- 21878054
TI  - Obesity and metabolic syndrome during the menopause transition in Serbian women.
AB  - BACKGROUND: Abdominal obesity and metabolic syndrome are known to increase in
      prevalence from premenopause to postmenopause. Both are well recognized
      predictors of cardiovascular disease and diabetes in women. Aims The primary
      objective of this study was to assess the presence of obesity and metabolic
      syndrome during the menopause transition in Serbian women who attended health
      care centers. The secondary objective was to evaluate the prevalence of ischemic
      heart disease, stroke and diabetes in this group. METHODS: Our results present a
      part of the national epidemiological cross-sectional study assessing prevalence
      of metabolic syndrome and obesity in Serbia. In all, 1076 women attending 20
      health-care centers were assessed. Women were divided into five groups:
      premenopausal, perimenopausal, early and late postmenopausal and geripausal.
      Medical history, waist circumference, blood glucose, lipids, and blood pressure
      were recorded. RESULTS: The mean body mass index of all women was 28.5 +/- 4.9
      kg/m(2). The mean waist circumference of all women was 92 +/- 12.5 cm. Both were
      significantly lower in premenopausal women than in other women. Metabolic
      syndrome was present in 72% of women, with a significant difference in prevalence
      between premenopausal women and other groups. High triglyceride levels and
      hypertension were the most commonly present components of metabolic syndrome.
      Ischemic heart disease, stroke and diabetes occurred significantly more often in
      postmenopausal and geripausal women. CONCLUSION: The majority of Serbian women
      attending health-care centers have abdominal obesity and metabolic syndrome which
      significantly increase in prevalence in the perimenopausal years. This indicates
      that preventive measures should be focused on diabetes and cardiovascular disease
      in the perimenopause.

PMID- 21878055
TI  - Risk factors for vitamin D deficiency in HIV-infected patients in the south
      central United States.
AB  - We evaluated the prevalence of serum 25-hydroxyvitamin D [25(OH)D] deficiency and
      the risk factors for vitamin D deficiency in HIV-infected patients in the South
      Central United States. The study consisted of a cross-sectional assessment of
      vitamin D levels in HIV-infected patients receiving routine clinical care from a
      private practice in Houston, Texas (latitude 29 degrees N). Vitamin D deficiency
      was defined as 25(OH)D less than 20 ng/ml (<50 nmol/liter). Two-hundred enrolled
      patients were surveyed with a vitamin D questionnaire to determine daily
      supplemental vitamin D intake, dietary vitamin D intake, and average sunlight
      exposure (minutes/day). Multivariate logistic regression analysis was used to
      determine significant risk factors for vitamin D deficiency. Median 25(OH)D was
      15.5 ng/ml (interquartile range 10.9-24.6) for the total population (n=200).
      Approximately, two-thirds (64%) of patients had vitamin D deficiency and 20.5%
      had severe vitamin D deficiency [25(OH)D <10 ng/ml or <25 nmol/liter]. In
      univariate analysis, African-American race, current tobacco use, increased body
      mass index (BMI), lower serum calcium level, no supplemental vitamin D use, and
      low daily supplemental and total daily vitamin D intake were significantly
      associated with vitamin D deficiency. In multivariate analysis, African-American
      race [adjusted odds ratio (AOR) 3.53 (95% confidence interval (CI) 1.83-6.82)],
      higher BMI [AOR 1.07 (95% CI 1.002-1.139)], and low daily vitamin D supplemental
      intake [AOR 0.997 (95% CI 0.996-0.999)] were significantly associated with
      vitamin D deficiency. No HIV factors including antiretroviral class use were
      significantly associated with either vitamin D deficiency or severe vitamin D
      deficiency. Vitamin D deficiency and severe vitamin D deficiency were highly
      prevalent in this HIV population. In the HIV population, African-Americans or
      patients with a high BMI may benefit from vitamin D supplementation.

PMID- 21878057
TI  - The neural correlates of empathy: experience, automaticity, and prosocial
      behavior.
AB  - Empathy is a critical aspect of human emotion that influences the behavior of
      individuals as well as the functioning of society. Although empathy is
      fundamentally a subjective experience, no studies have yet examined the neural
      correlates of the self-reported experience of empathy. Furthermore, although
      behavioral research has linked empathy to prosocial behavior, no work has yet
      connected empathy-related neural activity to everyday, real-world helping
      behavior. Lastly, the widespread assumption that empathy is an automatic
      experience remains largely untested. It is also unknown whether differences in
      trait empathy reflect either variability in the automaticity of empathic
      responses or the capacity to feel empathy. In this study, 32 participants
      completed a diary study of helping behavior followed by an fMRI session,
      assessing empathic responses to sad images under three conditions: watching
      naturally, under cognitive load, and while empathizing. Across conditions, higher
      levels of self-reported experienced empathy were associated with greater activity
      in medial PFC (MPFC). Activity in MPFC was also correlated with daily helping
      behavior. Self-report of empathic experience and activity in empathy-related
      areas, notably MPFC, were higher in the empathize condition than in the load
      condition, suggesting that empathy is not a fully automatic experience.
      Additionally, high trait empathy participants displayed greater experienced
      empathy and stronger MPFC responses than low trait empathy individuals under
      cognitive load, suggesting that empathy is more automatic for individuals high in
      trait empathy. These results underline the critical role that MPFC plays in the
      instantiation of empathic experience and consequent behavior.

PMID- 21878056
TI  - Effects of age on the neural correlates of familiarity as indexed by ERPs.
AB  - ERPs were recorded from samples of young (18-29 years) and older (63-77 years)
      participants while they performed a modified "remember-know" recognition memory
      test. ERP correlates of familiarity-driven recognition were obtained by
      contrasting the waveforms elicited by unrecollected test items accorded
      "confident old" and "confident new" judgments. Correlates of recollection were
      identified by contrasting the ERPs elicited by items accorded "remember" and
      confident old judgments. Behavioral analyses revealed lower estimates of both
      recollection and familiarity in older participants than in young participants.
      The putative ERP correlate of recollection-the "left parietal old-new effect"-was
      evident in both age groups, although it was slightly but significantly smaller in
      the older sample. By contrast, the putative ERP correlate of familiarity-the
      "midfrontal old-new effect"-could be identified in young participants only. This
      age-related difference in the sensitivity of ERPs to familiarity was also evident
      in subgroups of young and older participants, in whom familiarity-based
      recognition performance was equivalent. Thus, the inability to detect a reliable
      midfrontal old-new effect in older participants was not a consequence of an age
      related decline in the strength of familiarity. These findings raise the
      possibility that familiarity-based recognition memory depends upon qualitatively
      different memory signals in older and young adults.

PMID- 21878058
TI  - "Ventilatory management of asphyxiated infant during hypothermia".
AB  - Hypothermia is used for its neuroprotective effect in perinatal asphyxia.
      Mechanical ventilation is often used as a supportive therapy for severe
      asphyxiated infants who can present various degrees of respiratory failure.
      Animal studies demonstrated a protective effect of cooling on the lungs due to
      reduced ventilatory requirements. Even if actual knowledge on the effects of
      hypothermia and rewarming on respiratory parameters during mechanical ventilation
      is limited, nevertheless human studies seem to demonstrate that hypothermia is
      safe and does not cause significant changes in the level of respiratory supports.

PMID- 21878060
TI  - Short communication: a single step assay for rapid evaluation of inhibitors
      targeting HIV type 1 Tat-mediated long terminal repeat transactivation.
AB  - Human immunodeficiency virus (HIV) long terminal repeat (LTR) promoter-mediated
      gene expression is regulated by the viral Tat protein that relieves a block to
      viral transcription elongation after binding with a viral hairpin loop RNA
      structure called the trans-activation-responsive region (TAR). Tat protein
      significantly up-regulates viral genome transcription and hence it has long been
      considered a potential target for antiretrovirals. Here we report the
      construction of a plasmid containing an HIV-1 LTR-driven reporter cassette with a
      colinear tat gene under control of a viral promoter and thus conditionally
      configured for constitutive expression of reporter genes. Inhibition of
      luciferase reporter expression in a cell line harboring the plasmid in the
      presence of tat-targeted shRNA confirmed the specificity of the assay and a dose
      dependent reporter activity inhibition by the fluoroquinoline derivative K-37, a
      class of small RNA binding molecule that inhibits Tat and other RNA-dependent
      transactivations, further validated the method. Subsequently we also made a
      lentiviral vector (LV) containing the same transcription units and derived a
      stable cell line using the said LV and similar dose-dependent inhibition was
      documented using K-37. This quick and sensitive reporter-based method is the
      simplest screening assay for putative inhibitors of HIV-1 Tat-induced LTR-driven
      gene expression requiring test material addition as the only manipulation.

PMID- 21878059
TI  - Insulin resistance and cognition among HIV-infected and HIV-uninfected adult
      women: the Women's Interagency HIV Study.
AB  - Cognitive impairment remains prevalent in the era of combination antiretroviral
      therapy (cART) and may be partially due to comorbidities. We postulated that
      insulin resistance (IR) is negatively associated with cognitive performance. We
      completed a cross-sectional analysis among 1547 (1201 HIV(+)) women enrolled in
      the Women's Interagency HIV Study (WIHS). We evaluated the association of IR with
      cognitive measures among all WIHS women with concurrent fasting bloods and
      cognitive testing [Trails A, Trails B, and Symbol Digit Modalities Test (SDMT)]
      using multiple linear regression models. A smaller subgroup also completed the
      Stroop test (n=1036). IR was estimated using the Homeostasis Model Assessment
      (HOMA). Higher HOMA was associated with poorer performance on the SDMT, Stroop
      Color-Naming (SCN) trial, and Stroop interference trial, but remained
      statistically significant only for the SCN in models adjusting for important
      factors [beta=3.78 s (95% CI: 0.48-7.08), p=0.025, for highest vs. lowest
      quartile of HOMA]. HIV status did not appear to substantially impact the
      relationship of HOMA with SCN. There was a small but statistically significant
      association of HOMA and reduced neuropsychological performance on the SCN test in
      this cohort of women.

PMID- 21878062
TI  - Evidence-based platelet transfusion recommendations in neonates.
AB  - Even though for certain varieties of neonatal thrombocytopenia, intravenous
      immunoglobulin or corticosteroids are recommended as treatments, platelet
      transfusions represent the only specific therapy currently available for most
      thrombocytopenic neonates in NICUs. The majority of these NICU platelet
      transfusions, up to 98% in some recent reports, are given to prevent, rather than
      to treat, bleeding. The trigger limit of platelet count to prophylactically treat
      non-bleeding patients is generally arbitrary. A complete definition, of the
      benefits and the risks of prophylactic platelet transfusions in thrombocytopenic
      neonates is necessary. In fact, there is great variability worldwide in neonatal
      platelet transfusion practice, due to the lack of concrete evidence to guide
      transfusion decisions. Evidence-based guidelines do not exist to decide when
      platelet transfusion should be given. The practice of neonatal platelet
      transfusions is based almost entirely on expert opinion and reasoning.
      Consequently, these practices, not supported by definitive data, vary widely. To
      increase benefits and safety, new widespread changes in platelet transfusion
      guidelines are necessary. New transfusion paradigms should not be based on
      reasoning alone, but on important experimental validation. The neonatologists
      would better accept them and more closely adhere to.

PMID- 21878061
TI  - Italia-Netherland PhD Program: the I.O. PhD Research Program.
AB  - In the framework of long-term scientific collaboration among the founder members
      coming from Holland and Italy there was a growing consensus to activate a
      philosophical doctorate (PhD) program, involving young Italian researchers in the
      field of perinatal medicine, neonatology and pediatrics. The aims were to promote
      excellence in research, offering to young Italian physicians the opportunity to
      maturate an International research experience leading to PhD degree, and to
      promote human and technological improvement energies in perinatal, neonatal and
      pediatrics research. Thus, an official collaboration among the Dutch Universities
      from Maastricht and Utrecht and the Italian Children's Hospital from Alessandria,
      has been activated on March 1st 2010, finalized to the PhD program. The
      experimental phase included the selection of projects and relative candidates
      after an interview-selection focusing on their scientific attitudes and the
      availability on their research projects. Candidates' selection started on May
      2010 and on September 29th ten projects and candidates have been approved by the
      scientific commission. Research topics included: perinatal asphyxia, aging and
      the origin of adulthood neurodegenerative disease, neuroprotective strategies,
      biochemical pulmonology, intrauterine growth retardation and perinatal
      teratology. To date, all projects have been approved by local Ethics Committee
      from the University/Hospital of origin of the candidates. Five manuscripts have
      been published and/or submitted to international Journals regarding pneumology,
      perinatal asphyxia and teratology, whilst about 60-70% of data regarding clinical
      studies have already been collected.

PMID- 21878063
TI  - [Cystatin C level is independently related to risk of unfavorable outcome after
      acute coronary syndrome in individuals with normal or moderately reduced renal
      function].
AB  - We studied relation between cystatin C level and risk of unfavorable outcome
      (unstable angina, fatal and nonfatal myocardial infarction [MI], fatal and
      nonfatal stroke, and death) in patients stabilized after exacerbation of ischemic
      heart disease. Patients (n=272) were included on day 10 after onset of acute
      coronary syndrome. No relationship between studied outcomes and cystatin was
      found in a group as a whole. In patients with normal of slightly reduced renal
      function (glomerular filtration rate more or equal 60 ml/min/1.73 m2) unfavorable
      outcomes were independently associated with history of myocardial infarction and
      stroke, elevated levels of brain natriuretic peptide and cystatin. In subjects
      with moderately or severely reduced renal function elevation of cystatin level
      lost its significance. Risk of development of unfavorable outcomes among these
      subjects was independently related to history of MI and GFR <60 ml/min/1.73 m2
      (OR 2.130, 95% CI 1.010-4,489; =0,047). Our data confirm possibility of use of
      cystatin C level measured early after ACS in patients with normal or slightly
      lowered renal function as a parameter characterizing risk of cardiovascular
      complications and death.

PMID- 21878064
TI  - [The (PRIMA) Study. Comparison of clinical effect of trimetazidine MR in men and
      women].
AB  - Main objective of epidemiological part of the (PRIMA) study was elucidation of
      special characteristics of Russian population of patients with stable angina and
      more precise characterization of variety and volume of drug and nondrug therapy
      used in patients with stable angina in Russian Federation. In clinical part of
      the PRIMA program we assessed efficacy and safety of standard antianginal therapy
      in combination with trimetazidine with modified release of active substance (MR)
      in standard therapeutic dose in patients with stable angina after myocardial
      infarction. According to results of the study prescription of trimetazidine MR
      was followed by improvement of clinical course of the disease. This manifested as
      decrease of average number of attacks per week, reduction of mean weekly
      consumption of short acting nitrates, improvement of quality of life, lessening
      of severity of main clinical manifestations of chronic heart failure, and
      lowering of its functional class. It is necessary to emphasize that analysis of
      results of the PRIMA study has revealed similar efficacy of trimetazidine MR in
      men and women what allows to recommend this metabolic myocardial cytoprotector to
      patients with ischemic heart disease irrespective of gender.

PMID- 21878065
TI  - [Content of tumor necrosis factor- and growth transforming factor- in patients
      with ischemic heart disease after coronary artery bypass grafting].

PMID- 21878066
TI  - [Effect of the presence of a drug in the list of supplementary drug provision on
      compliance to its administration by outpatients with arterial hypertension].
AB  - Aim of the study was to investigate relationship between the presence of a drug
      in the list of supplementary drug provision (SDP) and compliance to its
      consumption by outpatients with arterial hypertension as well as determination of
      the place of SDP in a row of other factors affecting compliance to treatment.
      Methods. Patients (men and women) older than 18 years with initial level of
      office systolic arterial pressure (AP) 140-179 mm Hg and diastolic AP up to 100
      mm Hg who visited regional internist. The study was conducted at the base of 82
      Moscow polyclinics with participation of 185 physicians and 5474 patients. In all
      patients besides general clinical examination with office AP measurement
      calculation of body mass index and assessment of risk factors and concomitant
      therapy were carried out. All patients assessed themselves their self feeling
      with the use of visual-analog scale (VAS). Compliance of patients to
      antihypertensive therapy was evaluated with the help of the Moriski - Green test.
      Fact of continuous use of antihypertensive drugs received by patients within
      framework of the SDP system was necessarily obligatory. For final analysis 4816
      ambulatory cards were selected. Results. Portion of patients with low compliance
      to therapy was greatly than that of patients with high compliance to therapy
      (61.1 vs. 38.9%, respectively, p=0.00001). Inclusion into analysis of additional
      factor (presence of CHD) reduced contribution of SDP to compliance to 25%, but it
      remained as before significant (p<0.0007). However addition to these factors of
      other parameters such as presence of diabetes mellitus or tonometer at home
      completely leveled effect of SDP on compliance to therapy (p<0.12). Conclusion.
      Presence of drugs in the SDP list significantly elevates compliance to therapy.
      However SDP does not appear the only independent predictor of high compliance. If
      SDP is considered together with other determining factors (presence of
      concomitant IHD and diabete, readiness to spend money for tonometer) its role as
      independent factor of high compliance is diminished and loses significance.

PMID- 21878067
TI  - [Application of coenzyme Q(10) in combination therapy of arterial hypertension].
AB  - We studied effect of coenzyme Q(10) on 24-hour blood pressure profile and
      function of vascular endothelium in patients with essential hypertension.
      Coenzyme Q(10) was used as a component of combination therapy comprising
      angiotensin converting enzyme inhibitor enalapril. Administration of coenzyme
      Q(10) in combination with traditional antihypertensive therapy promoted
      normalization of vascular endothelial function and more effective correction of
      24-hour blood pressure profile. These findings allow to consider the use of
      coenzyme Q(10) as promising component of combination therapy of arterial
      hypertension.

PMID- 21878068
TI  - [Clinical value of brain natriuretic peptide level in patients with atrial
      fibrillation].
AB  - PURPOSE of this investigation was to study correlation between brain natriuretic
      peptide (BNP), extent of cardiac abnormalities, and six minute walk test (6-MWT)
      in order to asses diagnostic value of BNP in patients with trial fibrillation
      (F), heart failure (HF) and preserved systolic function. MATERIAL AND METHODS:
      Sixty five patients with history of hypertension, permanent F, and shortness of
      breath in absence of signs of congestive hemodynamics were included into this
      study. RESULTS: Concentration of BNP in serum n the day of inclusion was
      significantly inversely related to results of 6-MWT, and positively related to
      left atrial dilation, to hospitalizations due to cardiovascular causes.
      CONCLUSION: Measurement of BNP concentration in patients with AF allows to
      diagnose HF at early stages and to predict cardiovascular complications.

PMID- 21878069
TI  - [The study of microcirculation in walls of chambers of the heart in patients with
      aortic stenosis in dependence on heart failure stage].
AB  - We studied microcirculatory blood flow (MBF) by laser Doppler flowmetry (LDF) in
      52 patients with stage III-IV aortic stenosis (AS) and class II-IV chronic heart
      failure (CHF). MBF was assessed in walls of right and left cardiac chambers
      before and after correction of the defect. Aim of this study was to assess
      functional state of MBF in walls of different chambers of the heart before and
      after defect correction in patients with AS at various stages of CHF. We
      distinguished 2 groups of patients: group 1 with class II CHF, group 2 with class
      III-IV CHF. In group 2 compared with group 1 before and after AS correction of AS
      we found the lowest level of MBF in walls of left cardiac chambers and right
      atrium and highest parameters of the left ventricular and atrial function
      according to echocardiography data. Progression of anatomic-functional changes of
      left ventricle at the background of AS and development of CHF is characterized by
      lowering of MBF volume velocity in walls of left cardiac chambers.

PMID- 21878070
TI  - [he use ethylmethylhydroxypyridine succinate in the treatment of patients with
      heart failure].
AB  - We studied impact of ethylmethylhydroxypyridine succinate n the course of chronic
      heart failure during 3 years follow-up after myocardial infarction. Dynamics of
      objective and subjective parameters was assessed in 100 patients; 48 patients
      received conventional therapy (control group) and 52 patients received
      conventional therapy plus ethylmethylhydroxypyridine succinate (main group).
      Addition of ethylmethylhydroxypyridine succinate resulted in decreases of rates
      of complications, mortality, and re-hospitalizations. Increases of myocardial
      contractile function, myocardial adaptation, as well as improvement of range of
      biochemical parameters were also observed. The latter changes were indicative of
      antioxidant, anti-inflammatory, anti-stress activities of
      Ethylmethylhydroxypyridine succinate. Moreover, antidepressant and antineurotic
      effects of complex therapy including ethylmethylhydroxypyridine succinate was
      confirmed.

PMID- 21878072
TI  - [Polymorphisms of 2B-adrenergic receptor and endothelial NO-Synthase genes in
      genesis of the hereditary sick sinus node syndrome].
AB  - In this work we have demonstrated for the first time on the clinico-genetic
      material association between hereditary sick sinus node syndrome (SSNS) ADRA2B
      and eNOS genes polymorphisms. We have established predominance of homozygote
      genotype of more rare DD allele in patients with SSNS (28%) compared with
      subjects of control group (8.99%). We have found predominance of heterozygote
      genotype 4a/4b in patients with SSNS compared with subjects of control group
      (41.8 and 25.39%, respectively). The data obtained allow to suggest that eNOS
      gene polymorphism might be associated with SSNS.

PMID- 21878071
TI  - [Eosinophilic cation protein and development of restenosis of drug covered
      stents].
AB  - Aim of the study was to assess activation of eosinophils as well as allergic and
      inflammatory reactions of the body in development of restenosis after
      implantation of stents with drug covering. We included into the study 32 patients
      with ischemic heart disease (IHD) and stable angina subjected to repeat coronary
      angiography during first year after endovascular myocardial revascularization
      with the help of stents with drug covering, and 11 healthy persons. Levels of
      eosinophilic cation protein (ECP), immunoglobulin E (IgE), and C-reactive protein
      (CRP) in blood plasma of patients and healthy persons was determined by
      immunoenzyme assay. According to results of angiographic study patients were
      divided into 2 groups: the first comprised 19 patients in whom no instent
      restenosis was found, the second comprised 13 patients in whom formation of
      restenosis at least in one stent was noted. Patients in these groups did not
      differ by age, sex, smokers and nonsmokers ratio, presence of hyperlipidemia, and
      angiographical characteristics of involved arteries. In patients with restenosis
      of stents blood plasma ECP level was 17.7 (11.2-24.0) g/ml and significantly
      higher than in patients without restenosis [9.0 (6.4-12.9) g/ml; p=0.017]. Blood
      level of IgE in these groups of patients did not differ [58.8 (42.1-164.0) and
      52.9 (12.8-76.1) mg/ml, respectively; p=0.40] and did not differ from IgE level
      in blood of healthy volunteers [32.0 (21.2-80.8) mg/ml; p=0.91]. CRP level in
      patients with IHD was higher than in healthy volunteers [0.36 (0.1-0.75) mg/ml;
      p=0.0008)], but did not differ significantly in groups of patients with and
      without restenosis [2.38 (0.30-4.08) and 1.63 (0.61-2.47) mg/ml, respectively;
      p=0.52]. It was found that in the group of patients with low blood level of ECP
      (<11 g/ml) restenoses were revealed in 19% while in the group with higher blood
      level of ECP (>11 g/ml) - in 62% of cases (p=0,019). In patients subjected to
      coronary stenting with higher level of ECP in blood we noted more frequent
      development of restenoses than in patients with low level of this protein. The
      data obtained allow to suggest presence of relationship between development of
      restenosis and elevated activity of eosinophilic granulocytes in patients with
      IHD after revascularization.

PMID- 21878073
TI  - [Fifteen years experience of the use of magnesium preparations in patients with
      mitral valve prolapse].
AB  - We followed for 15 years 31 patients with mitral valve prolapse (MVP) who during
      follow-up regularly took orotic acid (1500 mg/day) for 3 months twice a year. We
      revealed peculiarities of dynamics of clinical picture, their interrelation with
      phenotypic manifestations of connective tissue dysplasia, changes of
      electrocardiogram, structure of valvular apparatus of the heart, state of
      vegetative homeostasis, changes of levels and 24-hour profile of arterial
      pressure, tone of sympathetic and parasympathetic parts of vegetative nervous
      system. We noted significant reduction of mean and maximal heart rate, number of
      episodes of tachycardia, duration of QTc intervals, incidence of paroxysmal
      supraventricular and ventricular extrasystoles. We fixed statistically
      significant lowering of maximal systolic and diastolic arterial pressure,
      hypertensive burden and elevated variability of systolic and diastolic arterial
      pressure. Data of retrospective analysis showed absolute normalization of these
      parameters in all studied patients. Decrease of the tone of sympathetic part of
      vegetative nervous system was also established. There was 2 to fold decrease of
      number of persons with sympathicotonia, 3 to fold increase of those with
      vagotonia, and 5 times increase of number of patients with equal tone of
      sympathetic and parasympathetic parts. Regular use of magnesium salt of orotic
      acid was associated with significant elevation of quality of life of patients
      with MVP. Clinically valuable improvement of work and social life scores was
      noted in 54.8%, of personal life score - in 45.2% of individuals. In half of
      patients with MVP index of efficacy of therapy with orotic acid was significant.

PMID- 21878074
TI  - [Microvolt T-wave alternans as a novel method of analysis of changes of
      repolarization phase and detection of latent electrical instability of the
      myocardium].
AB  - This review considers of modern concepts of microvolt T-wave alternans (TWA): its
      pathophysiological basis at cellular level, particulars of quantitative analysis
      of TWA, modulating effects of autonomic nervous system and drugs, prognostic
      efficacy in predicting susceptibility to ventricular arrhythmia in comparison
      with other modern prognostic factors of sudden cardiac death.

PMID- 21878075
TI  - [Combination therapy of arterial hypertension: the role of triple component
      combinations].

PMID- 21878076
TI  - [Analysis of efficacy and safety of administration of moxonidine in patients with
      arterial hypertension and hypertensive crises].
AB  - In the review we present detailed analysis of antihypertensive action of 3-nd
      generation sympatholytic moxonidine. Due to selective interaction with
      imidazoline I1-receptors moxonidine diminishes sympathetic activity causing
      lowering of peripheral vascular resistance. This leads to significant lowering of
      systolic and diastolic arterial pressure. Efficacy and safety of the drug has
      been shown both for the management of uncomplicated hypertensive crises and long
      term treatment of arterial hypertension (AH). Appropriateness of the use of
      moxonidine in patients with AH combined with diabetes mellitus, metabolic
      syndrome, chronic obstructive pulmonary disease has been confirmed. Moxonidine is
      well tolerated; its bioavailability after oral intake reaches 90%. The drug
      produces neither hypotensive "first dose" nor rebound effects.

PMID- 21878077
TI  - [Platelet aggregation upon acetylsalicylic acid and clopidogrel treatment and
      glycoprotein IIb/IIIa content in patients with acute coronary syndrome].
AB  - Interaction between aggregating activity of platelets and glycoprotein (GP)
      IIb/IIIa (fibrinogen receptor) content on their surface was investigated in
      patients with acute coronary syndrome (ACS). Eighty nine ACS patients were
      included into the study - 69 with and 20 without elevation of ST segment. Blood
      was collected within the first hour of admission to the clinic (1 day), and then
      at 3-5 and 8-12 days. All patients received standard antiaggregant therapy -
      acetylsalicylic acid - ASA (thromboxane A2 synthesis inhibitor) and clopidogrel
      (ADP receptor antagonist). Platelet aggregation was analyzed at the first time
      point when patients had already taken ASA but not clopidogrel, and then (3-5 and
      8- 12 days) upon combined therapy with both preparations. Aggregation was induced
      by 5 and 20 uM ADP and measured by turbidimetric method. In comparison with the
      initial level (1 day, ASA) at days 3-5, i.e. after development of clopidogrel
      effect, platelet aggregation was decreased by 54 and 40% upon its stimulation
      with 5 and 20 uM ADP, and was not further changed at days 8-12. GP IIb/IIIa
      content on platelet surface was determined by binding of 125I-labelled monoclonal
      antibody CRC64. GP IIb/IIIa number varied from 31100 to 73000 per platelet with
      the mean level of 48500 +/- 8400 (mean +/- standard deviation). No differences
      were detected between mean GP IIb/IIIa number at 1, 3-5 and 8-12 days after ACS
      onset. Upon repeat GP IIb/IIIa measurement coefficient of variation was 6.1%
      demonstrating the stability of this parameter in each patient. Positive
      correlation between platelet aggregation and GP IIb/IIIa content was detected at
      the first day - correlation coefficients (r) 0.425 and 0.470 for 5 and 20 uM ADP
      (n=57, p<0.001). However positive association between these parameters was not
      revealed at 3-5 and 8-12 days, when patients received not only ASA but
      clopidogrel as well (r from -0.054 to -0.237, p>0.05). These results indicates
      that variations of GP IIb/IIIa content affect platelet aggregating activity
      within first hours of ACS upon ASA treatment. However after saturation with
      clopidogrel this factor has no significant influence on platelet aggregation, at
      least on aggregation induced by ADP which receptor is the target of this
      antiaggregant. Under such conditions aggregation parameters are presumably
      influenced first of all by individual characteristics of clopidogrel
      pharmacokinetics.

PMID- 21878078
TI  - [Comparative assessment of inhospital course and outcome of treatment in patients
      with q-wave acute myocardial infarction with and without endovascular myocardial
      reperfusion].

PMID- 21878079
TI  - [Dynamics of echocardiographical parameters of left ventricular remodelingin
      patients with acute myocardial infarction after successful primary angioplasty in
      dependence on the state of coronary blood flow before intervention].

PMID- 21878080
TI  - [Possibilities of improvement of prognosis in patients with type 2 diabetes
      mellitus after coronary interventions].
AB  - We present results of investigation of fenofibrate in patients with ischemic
      heart disease and type 2 diabetes mellitus after myocardial revascularization at
      various terms of its administration. We have shown its efficacy in correction of
      diabetic dyslipidemia, positive influence on clinical status and long term result
      of coronary intervention. We have established that early (first 7 days)
      prescription of fenofibrate - Tricor to patients with ischemic heart disease and
      type 2 diabetes mellitus after myocardial revascularization lowers number of
      diagnostic coronary angiograms and repeat percutaneous coronary interventions by
      11% during first year of follow-up.

PMID- 21878081
TI  - [Comparison of efficacy and safety of treatment with drugs of clopidogrel in
      patients after coronary artery stenting].
AB  - Proof of clinical equivalence of generic and original dugs - the way to lessen
      cost of therapy of patients while providing comparable clinical effects. We
      present in this paper results of 1 year follow-up of 115 patients receiving
      Egithromb or Plavics after coronary artery stenting. Comparable clinical efficacy
      and safety of Egithromb and Plavics has been established.

PMID- 21878082
TI  - [Efficacy of fixed combination amlodipine/valsartan in hospitalized patients with
      hypertensive disease].
AB  - Efficacy and tolerability of fixed amlodipine/valsartan combination was studied
      in 86 patients with hypertensive disease hospitalized in departments of general
      internal medicine or cardiology. All patients had indications for
      antihypertensive therapy and were randomized either to fixed combination
      amlodipine/valsartan (n=43) or to therapy which corresponded to the hospital
      formulary (n=43). Correction of antihypertensive therapy was performed by
      treating physician at daily rounds. Self-control of blood pressure (BP) was
      performed by patients with the use of UA767PC apparatus. Results of BP self
      control were compared with clinical measurements in order to detect concealed
      inefficacy of treatment. Results. Rate of achievement of target BP with fixed
      combination amlodipine/valsartan (93%) was comparable with that on traditional
      therapy (90%). But the use of fixed combination amlodipine/valsartan compared
      with traditional therapy was associated with lower clinical and self measured BP,
      quicker achievement of target BP (5.8+/-2.3 and 9.2+/-1.8 days, respectively,
      p<0.05), lesser number of antihypertensive drugs (2.5+/-0.6 and 3.0+/-0.9 days,
      respectively), lower rate of concealed inefficacy of treatment (12 and 31%,
      respectively, p<0.05). Conclusions. We have demonstrated appropriateness of
      inhospital administration of fixed amlodipine/valsartan combination as an
      approach allowing to achieve target BP in shorter time, with the use of fewer
      antihypertensive drugs, and diminishing concealed inefficacy of treatment.

PMID- 21878083
TI  - [Echocardiographic parameters in patients with Wolf-Parkinson-White syndrome
      before and during one year after radiofrequency catheter ablation of accessory
      atrioventricular junction].
AB  - We present in this paper results of assessment of morphofunctional state of
      myocardium in patients with the Wolf-Parkinson-White syndrome before and during
      one year after radiofrequency catheter ablation (RFA) of accessory
      atrioventricular junction (AAVJ) and comparison of them with analogous parameters
      of the group of healthy volunteers as well as in dependence on
      electrophysiological properties of AAVJ and its localization. One hundred sixty
      patients took part in the conducted study: main group comprised 160 patients
      (80.7%) with WPW syndrome (114 men [81.4%], 26 women [18.6%], mean age 39.5+/
      15.3 years), comparison group comprised 20 practically healthy persons (15 men
      [75.0%], 5 women [25%], mean age 41.9+/-5.3 years). All main group patients were
      subjected to endocardial electrophysiological investigation and RFA of AAVJ.
      Transthoracic echocardiography (EchoCG) was carried out in patients of main group
      before and in 2, 6, and 12 months after operation of RFA of AAVJ, and once in
      control group. Analysis of parameters of central hemodynamics according to data
      of transthoracic EchoCG in patients with WPW syndrome before RFA of AAVJ
      demonstrated that before conduct of operative intervention no significant
      differences were revealed in the studied parameters compared with analogous
      characteristics of the clinical comparison group. During whole period of dynamic
      observation (2, 6, and 12 months after fulfilled RFA of AAVJ) in patients with
      WPW syndrome the studied parameters of central hemodynamics did not undergo
      substantial changes compared with initial characteristics. We failed to establish
      significant differences of EchoCG parameters in patients with WPW syndrome in
      dependence on electrophysiological properties of AAVJ (concealed, manifest) and
      on AAVJ localization (right, left, septal). According to EchoCG data in patients
      with WPW syndrome so called "minor" anomalies of development of connective tissue
      of the heart were diagnosed in 69 (49.3%) patients while in control group - in 2
      (10%) patients.

PMID- 21878084
TI  - [Clinical value of antracycline toxicity: modern approaches to diagnosis,
      prevention, and treatment].
AB  - In this literature review we present analysis of various aspects of the problem
      of cardiotoxicity of antracyclines used for the treatment of the breast cancer.
      We consider mechanisms of their cardiotoxic action, role of risk factors,
      clinical manifestations of acute and chronic cardiotoxicity, and dependence of
      their severity on treatment duration and drug dose. We give data on contemporary
      methods of diagnostics of early toxic cardiac effects of antracyclines from the
      side of cardiovascular system. We also conducted assessment of possibility of
      prevention of toxic action of antracyclines with the use of combination of
      different methods including dose sparing regimens and schemes of treatment,
      combinations of drugs, use of cardioprotectors as well as novel preparations from
      the antracycline group, possessing lesser cardiotoxicity. Clinical and
      experimental data on the treatment of manifestations of cardiotoxicity with
      consideration of pathogenetic mechanisms of their development are given.

PMID- 21878085
TI  - [Cyclooxygenase inhibitors and antiplatelet effect of acetylsalicylic acid.
      selective approach to nonsteroidal anti-inflammatory drugs in cardiological
      practice].
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) represent class of medicines which
      is wide concerning chemical structure and mechanism of action. In the light of
      contradictory data on efficacy and safety of NSAID in cardiovascular patients
      selection of most appropriate NSAID (basing on profile of efficacy and safety) in
      patients receiving continuous therapy with low dose aspirin appears to be a
      problem. In this paper we discuss peculiarities of drug interaction between
      cyclooxygenase inhibitors and acetylsalicylic acid, and principles of selection
      of adequate NSAI.

PMID- 21878086
TI  - [Atrial fibrillation: novel possibilities of anticoagulant therapy in patients
      subjected to cardioversion].

PMID- 21878087
TI  - [Hypertension, obesity, erectile dysfunction. What kind of drug to choose].
AB  - Hypertension is one of the most common cardiovascular diseases. The development
      and progression of hypertension is associated with prolonged hyper activation of
      the renin-angiotensin-aldosterone system. ACE inhibitors and angiotensin receptor
      blockers (ARBs) are highly effective medicines and are widely used in the
      treatment of cardiovascular diseases: hypertension, congestive heart failure,
      coronary heart disease. The main pharmacological effects of ACE inhibitors and
      ARBs are hypotensive, neurohumoral, antiproliferative, cardio- and
      nefroprotective functions, as well as constantly improving endothelial function.
      In accordance with the article, hypertensive effectiveness, tolerability and
      organ-protective properties of valsartan are noticeable among patients with
      hypertension, obesity and erectile dysfunction, taking this medicine.

PMID- 21878088
TI  - [ACC/AHA/ESC 2006 guidelines for management of patients with ventricular
      arrhythmias and the prevention of sudden death].

PMID- 21878089
TI  - Precocious puberty in an infant with hepatoblastoma: a case report.
AB  - INTRODUCTION: The syndrome of isosexual precocious puberty associated with
      primary malignant hepatic tumors is rare. All previously reported cases in the
      literature are old and prognosis was grim. CASE PRESENTATION: We present the case
      of a 15-month-old Asian male baby who presented with precocious puberty
      associated with hepatoblastoma. Serum concentrations of alpha-fetoprotein and
      free testosterone were elevated, as was beta human chorionic gonadotropin
      hormone. He was treated with six courses of chemotherapy and underwent surgery.
      His surface markers as well as free testosterone level returned to normal during
      therapy. The child has now been off therapy for 18 months with no evidence of
      tumor recurrence at follow-up. CONCLUSION: Virilizing hepatoblastoma is rare and
      reported with poor outcome, but the development of new chemotherapeutic agents
      and complete surgical resection are promising.

PMID- 21878090
TI  - Towards the development of novel Trypanosoma brucei RNA editing ligase 1
      inhibitors.
AB  - BACKGROUND: Trypanosoma brucei (T. brucei) is an infectious agent for which drug
      development has been largely neglected. We here use a recently developed computer
      program called AutoGrow to add interacting molecular fragments to S5, a known
      inhibitor of the validated T. brucei drug target RNA editing ligase 1, in order
      to improve its predicted binding affinity. RESULTS: The proposed binding modes of
      the resulting compounds mimic that of ATP, the native substrate, and provide
      insights into novel protein-ligand interactions that may be exploited in future
      drug-discovery projects. CONCLUSIONS: We are hopeful that these new predicted
      inhibitors will aid medicinal chemists in developing novel therapeutics to fight
      human African trypanosomiasis.

PMID- 21878091
TI  - Simultaneous DNA and RNA isolation from brain punches for epigenetics.
AB  - BACKGROUND: Epigenetic modifications such as DNA methylation play an important
      role for gene expression and are regulated by developmental and environmental
      signals. DNA methylation typically occurs in a highly tissue- and cell-specific
      manner. This raises a severe challenge when studying discrete, small regions of
      the brain where cellular heterogeneity is high and tissue quantity limited.
      Because gene expression and methylation are often tightly linked it appears of
      interest to compare both parameters in the same sample. FINDINGS: We present a
      refined method for the simultaneous extraction of DNA for bisulfite sequencing
      and RNA for expression analysis from small mouse brain tissue punches. This
      method can also be easily adapted for other small tissues or cell populations.
      CONCLUSIONS: The method described herein results in DNA and RNA of a quantity and
      quality permitting highly reliable bisulfite analysis and quantitative RT-PCR
      measurements, respectively.

PMID- 21878092
TI  - A Guide for applying a revised version of the PARIHS framework for
      implementation.
AB  - BACKGROUND: Based on a critical synthesis of literature on use of the Promoting
      Action on Research Implementation in Health Services (PARIHS) framework,
      revisions and a companion Guide were developed by a group of researchers
      independent of the original PARIHS team. The purpose of the Guide is to enhance
      and optimize efforts of researchers using PARIHS in implementation trials and
      evaluations. METHODS: Authors used a planned, structured process to organize and
      synthesize critiques, discussions, and potential recommendations for refinements
      of the PARIHS framework arising from a systematic review. Using a templated form,
      each author independently recorded key components for each reviewed paper; that
      is, study definitions, perceived strengths/limitations of PARIHS, other
      observations regarding key issues and recommendations regarding needed
      refinements. After reaching consensus on these key components, the authors
      summarized the information and developed the Guide. RESULTS: A number of
      revisions, perceived as consistent with the PARIHS framework's general nature and
      intent, are proposed. The related Guide is composed of a set of reference tools,
      provided in Additional files. Its core content is built upon the basic elements
      of PARIHS and current implementation science. CONCLUSIONS: We invite researchers
      using PARIHS for targeted evidence-based practice (EBP) implementations with a
      strong task-orientation to use this Guide as a companion and to apply the revised
      framework prospectively and comprehensively. Researchers also are encouraged to
      evaluate its use relative to perceived strengths and issues. Such evaluations and
      critical reflections regarding PARIHS and our Guide could thereby promote the
      framework's continued evolution.

PMID- 21878093
TI  - The effectiveness of Stepping Stones Triple P: the design of a randomised
      controlled trial on a parenting programme regarding children with mild
      intellectual disability and psychosocial problems versus care as usual.
AB  - BACKGROUND: Children with an intellectual disability are at increased risk of
      psychosocial problems. This leads to serious restrictions in the daily
      functioning of the children and to parental stress. Stepping Stones Triple P aims
      to prevent severe behavioural, emotional and developmental problems in children
      with a (intellectual) disability by enhancing parenting knowledge and skills, and
      the self-confidence of parents. This paper aims to describe the design of a study
      of the effectiveness of parenting counselling using Stepping Stones Triple P
      compared to Care as Usual. METHODS/DESIGN: The effects of Stepping Stones Triple
      P will be studied in a Randomised Controlled Trial. Parents of children aged 5-12
      years with an IQ of 50-85 will be recruited from schools. Prior to randomisation,
      parents complete a screening questionnaire about their child's psychosocial
      problems and their parenting skills. Subsequently, parents of children with
      increased levels of psychosocial problems (score on Strengths and Difficulties
      Questionnaire >= 14) will be invited to participate in the intervention study.
      After obtaining consent, parents will be randomised either to the experimental
      group (Stepping Stones Triple P) or to Care as Usual. The primary outcome is a
      change in the child's psychosocial problems according to parents and teachers.
      The secondary outcome is a change in parenting skills. Data will be collected
      before the start of the intervention, immediately after the intervention, and six
      months after. DISCUSSION: This paper presents an outline of the background and
      design of a randomised controlled trial to investigate the effectiveness of
      Stepping Stones Triple P, which aims to decrease psychosocial problems in
      children with a mild intellectual disability. Stepping Stones Triple P seems
      promising, but evidence on its effectiveness for this population is still
      lacking. This study provides evidence about the effects of this intervention in a
      community-based population of children with a mild intellectual disability. TRIAL
      REGISTRATION: Netherlands Trial Register (NTR): NTR2624.

PMID- 21878094
TI  - Genotypic and phenotypic diversity of Ralstonia pickettii and Ralstonia insidiosa
      isolates from clinical and environmental sources including High-purity Water.
      Diversity in Ralstonia pickettii.
AB  - BACKGROUND: Ralstonia pickettii is a nosocomial infectious agent and a
      significant industrial contaminant. It has been found in many different
      environments including clinical situations, soil and industrial High Purity
      Water. This study compares the phenotypic and genotypic diversity of a selection
      of strains of Ralstonia collected from a variety of sources. RESULTS: Ralstonia
      isolates (fifty-nine) from clinical, industrial and environmental origins were
      compared genotypically using i) Species-specific-PCR, ii) PCR and sequencing of
      the 16S-23S rRNA Interspatial region (ISR) iii) the fliC gene genes, iv) RAPD and
      BOX-PCR and v) phenotypically using biochemical testing. The species specific-PCR
      identified fifteen out of fifty-nine designated R. pickettii isolates as actually
      being the closely related species R. insidiosa. PCR-ribotyping of the 16S-23S
      rRNA ISR indicated few major differences between the isolates. Analysis of all
      isolates demonstrated different banding patterns for both the RAPD and BOX
      primers however these were found not to vary significantly. CONCLUSIONS: R.
      pickettii species isolated from wide geographic and environmental sources appear
      to be reasonably homogenous based on genotypic and phenotypic characteristics. R.
      insidiosa can at present only be distinguished from R. pickettii using species
      specific PCR. R. pickettii and R. insidiosa isolates do not differ significantly
      phenotypically or genotypically based on environmental or geographical origin.

PMID- 21878095
TI  - Physical activity, cardiorespiratory fitness, and metabolic syndrome in
      adolescents: a cross-sectional study.
AB  - BACKGROUND: In adults, there is a substantial body of evidence that physical
      inactivity or low cardiorespiratory fitness levels are strongly associated with
      the development of metabolic syndrome. Although this association has been studied
      extensively in adults, little is known regarding this association in adolescents.
      The aim of this study was to analyze the association between physical activity
      and cardiorespiratory fitness levels with metabolic syndrome in Brazilian
      adolescents. METHODS: A random sample of 223 girls (mean age, 14.4 +/- 1.6 years)
      and 233 boys (mean age, 14.6 +/- 1.6 years) was selected for the study. The level
      of physical activity was determined by the Bouchard three-day physical activity
      record. Cardiorespiratory fitness was estimated by the Leger 20-meter shuttle run
      test. The metabolic syndrome components assessed included waist circumference,
      blood pressure, HDL-cholesterol, triglycerides, and fasting plasma glucose
      levels. Independent Student t-tests were used to assess gender differences. The
      associations between physical activity and cardiorespiratory fitness with the
      presence of metabolic syndrome were calculated using logistic regression models
      adjusted for age and gender. RESULTS: A high prevalence of metabolic syndrome was
      observed in inactive adolescents (males, 11.4%; females, 7.2%) and adolescents
      with low cardiorespiratory fitness levels (males, 13.9%; females, 8.6%). A
      significant relationship existed between metabolic syndrome and low
      cardiorespiratory fitness (OR, 3.0 [1.13-7.94]). CONCLUSION: The prevalence of
      metabolic syndrome is high among adolescents who are inactive and those with low
      cardiorespiratory fitness. Prevention strategies for metabolic syndrome should
      concentrate on enhancing fitness levels early in life.

PMID- 21878096
TI  - Meta-analysis of estrogen response in MCF-7 distinguishes early target genes
      involved in signaling and cell proliferation from later target genes involved in
      cell cycle and DNA repair.
AB  - BACKGROUND: Many studies have been published outlining the global effects of
      17beta-estradiol (E2) on gene expression in human epithelial breast cancer
      derived MCF-7 cells. These studies show large variation in results, reporting
      between ~100 and ~1500 genes regulated by E2, with poor overlap. RESULTS: We
      performed a meta-analysis of these expression studies, using the Rank product
      method to obtain a more accurate and stable list of the differentially expressed
      genes, and of pathways regulated by E2. We analyzed 9 time-series data sets,
      concentrating on response at 3-4 hrs (early) and at 24 hrs (late). We found >1000
      statistically significant probe sets after correction for multiple testing at 3-4
      hrs, and >2000 significant probe sets at 24 hrs. Differentially expressed genes
      were examined by pathway analysis. This revealed 15 early response pathways,
      mostly related to cell signaling and proliferation, and 20 late response
      pathways, mostly related to breast cancer, cell division, DNA repair and
      recombination. CONCLUSIONS: Our results confirm that meta-analysis identified
      more differentially expressed genes than the individual studies, and that these
      genes act together in networks. These results provide new insight into E2
      regulated mechanisms, especially in the context of breast cancer.

PMID- 21878097
TI  - Upper limb artery segmental occlusions due to chronic use of ergotamine combined
      with itraconazole, treated by thrombolysis.
AB  - BACKGROUND: The ergotamine tartrate associated with certain categories of drugs
      can lead to critical ischemia of the extremities. Discontinuation of taking
      ergotamine is usually sufficient for the total regression of ischemia, but in
      some cases it could be necessary thrombolytic and anticoagulant therapy to avoid
      amputation. CASE REPORT: A woman of 62 years presented with a severe pain left
      forearm appeared 10 days ago, with a worsening trend. The same symptoms appeared
      after 5 days also in the right forearm. Physical examination showed the right arm
      slightly hypothermic, with radial reduced pulse in presence of reduced
      sensitivity. The left arm was frankly hypothermic, pulse less on radial and with
      an ulnar humeral reduced pulse, associated to a decreased sensitivity and
      motility.Clinical history shows a chronic headache for which the patient took a
      daily basis for years Cafergot suppository (equivalent to 3.2 mg of
      ergotamine).From about ten days had begun therapy with itraconazole for vaginal
      candidiasis. The Color-Doppler ultrasound shown arterial thrombosis of the upper
      limbs (humeral and radial bilateral), with minimal residual flow to the right and
      no signal on the humeral and radial left artery. RESULTS: Angiography revealed
      progressive reduction in size of the axillary artery and right humeral artery
      stenosis with right segmental occlusions and multiple hypertrophic collateral
      circulations at the elbow joint. At the level of the right forearm was
      recognizable only the radial artery, decreased in size. Does not recognize the
      ulnar, interosseous artery was thin. To the left showed progressive reduction in
      size of the distal subclavian and humeral artery, determined by multiple
      segmental steno-occlusion with collateral vessels serving only a thin hypotrophic
      interosseous artery.Arteriographic findings were compatible with systemic drug
      induced disease. The immediate implementation of thrombolysis, continued for 26
      hours, with heparin in continuous intravenous infusion and subsequent
      anticoagulant therapy allowed the gradual disappearance of the symptoms with the
      reappearance of peripheral pulses. CONCLUSION: Angiography showed regression of
      vasospasm and the resumption of flow in distal vessels. The patient had regained
      sensitivity and motility in the upper limbs and bilaterally radial and ulnar were
      present.

PMID- 21878098
TI  - Malignant peritoneal mesothelioma presenting as recurrent adhesion obstruction in
      general surgery: a case report.
AB  - INTRODUCTION: Malignant peritoneal mesothelioma is a well-described entity in
      many reports in the literature in which it has been associated with asbestosis.
      However, there is no information describing the gross appearance and cardinal
      features seen during laparotomy, hence it is easy for the unwary surgeon to miss
      the diagnosis of this rare condition. CASE PRESENTATION: A 49-year-old man of
      African descent presented to our hospital with a three-month history of weight
      loss, anorexia, abdominal distension, and general signs of cachexia and ascites
      on second presentation. At first presentation one year prior to this, he had
      undergone a laparotomy at our institution by a different team for intestinal
      obstruction secondary to adhesions with no biopsy taken. The patient's condition
      subsequently progressively deteriorated, and investigations including upper and
      lower gastrointestinal endoscopies and computed tomography of the abdomen were
      inconclusive, except for some free fluid in the peritoneal cavity and diffuse,
      mild thickening of the gut wall and mesentery. A second-look exploratory
      laparotomy revealed widespread nodular thickening of the visceral peritoneum with
      a striking, uniformly diffuse, erythematous, and velvety appearance. The
      peritoneal biopsy histology showed that the patient had malignant peritoneal
      mesothelioma. His condition deteriorated rapidly, and he died eight weeks after
      surgery. CONCLUSION: Our report aims to increase the diagnosing clinician's
      awareness of the cardinal features of malignant peritoneal mesothelioma and thus
      reduce diagnostic errors and delays in treatment.

PMID- 21878099
TI  - Fatal myocardial infarction associated with intravenous N-acetylcysteine error.
AB  - BACKGROUND: N-acetylcysteine is used to treat acetaminophen toxicity and is
      available in both intravenous and oral formulations. Our report describes a
      patient treated with intravenous N-acetylcysteine for acetaminophen toxicity who
      died after an anaphylactoid reaction following initiation of the infusion.
      OBJECTIVE: Clinicians should be aware of potential complications when deciding on
      which formulation of N-acetylcysteine to administer. CASE REPORT: A 53-year-old
      male presented with altered mental status after an overdose of
      acetaminophen/hydrocodone and carisoprodol. He had an acetaminophen level of 49
      mcg/ml with an unknown time of ingestion. The patient was admitted to the
      intensive care unit (ICU) on a naloxone drip and was started on intravenous N
      acetylcysteine (NAC) at the presumed dose of 150 mg/kg. Shortly after initiating
      the NAC infusion, the patient developed periorbital edema, skin rash, and
      hypotension. The infusion of N-acetylcysteine was immediately stopped and the
      patient required emergent intubation. Resuscitation was begun with intravenous
      fluids followed by the initiation of phenylephrine. He developed ST elevation in
      the inferior leads on his ECG. This evolved into an inferior myocardial
      infarction by ECG and cardiac enzymes. Echocardiogram showed global, severe
      hypokinesis with an ejection fraction of less than 20% in a patient with no pre
      existing cardiac history. Despite aggressive support, he died approximately 17
      hours after the initiation of intravenous NAC. Further investigation found a 10
      fold formulation error in his NAC loading dose. CONCLUSION: The intravenous
      formulation of NAC has a higher probability of significant adverse effects and
      complications not described with the oral formulation. Clinicians should be aware
      of these potential complications when deciding on which formulation to
      administer.

PMID- 21878100
TI  - The correlation between radiative surface defect states and high color rendering
      index from ZnO nanotubes.
AB  - Combined surface, structural and opto-electrical investigations are drawn from
      the chemically fashioned ZnO nanotubes and its heterostructure with p-GaN film. A
      strong correlation has been found between the formation of radiative surface
      defect states in the nanotubes and the pure cool white light possessing averaged
      eight color rendering index value of 96 with appropriate color temperature.
      Highly important deep-red color index value has been realized > 95 which has the
      capability to render and reproduce natural and vivid colors accurately. Diverse
      types of deep defect states and their relative contribution to the corresponding
      wavelengths in the broad emission band is suggested.

PMID- 21878101
TI  - Why are breastfeeding rates low in Lebanon? A qualitative study.
AB  - BACKGROUND: Breastfeeding is a cost-effective public health intervention that
      reduces infant morbidity and mortality in developing countries. In Lebanon,
      breastfeeding exclusivity and continuation rates are disappointingly low. This
      qualitative study aims at identifying barriers and promoters of breastfeeding in
      the Lebanese context by exploring mothers' perceptions and experiences in
      breastfeeding over a one year period. METHODS: We conducted focus group
      discussions in three hospitals in Beirut, Lebanon, and followed up 36
      breastfeeding mothers with serial in-depth interviews for one year post-partum or
      until breastfeeding discontinuation. RESULTS: Themes generated from baseline
      interviews revealed several positive and negative perceptions of breastfeeding.
      Longitudinal follow up identified insufficient milk, fear of weight gain or
      breast sagging, pain, sleep deprivation, exhaustion, or maternal employment, as
      reasons for early breastfeeding discontinuation. Women who continued
      breastfeeding for one year were more determined to succeed and overcome any
      barrier, relying mostly on family support and proper time management.
      CONCLUSIONS: Increasing awareness of future mothers about breast feeding
      difficulties, its benefits to children, mothers, and society at large may further
      promote breastfeeding, and improve exclusivity and continuation rates in Lebanon.
      A national strategy for early intervention during school years to increase young
      women's awareness may improve their self-confidence and determination to succeed
      in breastfeeding later. Moreover, prolonging maternity leave, having day-care
      facilities at work, creation of lactation peer support groups and hotlines, and
      training of doctors and nurses in proper lactation support may positively impact
      breastfeeding exclusivity and continuation rates. Further research is needed to
      assess the effectiveness of proposed interventions in the Lebanese context.

PMID- 21878102
TI  - Socio-demographic and AIDS-related factors associated with tuberculosis stigma in
      southern Thailand: a quantitative, cross-sectional study of stigma among patients
      with TB and healthy community members.
AB  - BACKGROUND: Tuberculosis (TB) remains one of the most important infectious
      diseases worldwide. A comprehensive approach towards disease control that
      addresses social factors including stigma is now advocated. Patients with TB
      report fears of isolation and rejection that may lead to delays in seeking care
      and could affect treatment adherence. Qualitative studies have identified socio
      demographic, TB knowledge, and clinical determinants of TB stigma, but only one
      prior study has quantified these associations using formally developed and
      validated stigma scales. The purpose of this study was to measure TB stigma and
      identify factors associated with TB stigma among patients and healthy community
      members. METHODS: A cross-sectional study was performed in southern Thailand
      among two different groups of participants: 480 patients with TB and 300 healthy
      community members. Data were collected on socio-demographic characteristics, TB
      knowledge, and clinical factors. Scales measuring perceived TB stigma,
      experienced/felt TB stigma, and perceived AIDS stigma were administered to
      patients with TB. Community members responded to a community TB stigma and
      community AIDS stigma scale, which contained the same items as the perceived
      stigma scales given to patients. Stigma scores could range from zero to 30, 33,
      or 36 depending on the scale. Three separate multivariable linear regressions
      were performed among patients with TB (perceived and experience/felt stigma) and
      community members (community stigma) to determine which factors were associated
      with higher mean TB stigma scores. RESULTS: Only low level of education, belief
      that TB increases the chance of getting AIDS, and AIDS stigma were associated
      with higher TB stigma scores in all three analyses. Co-infection with HIV was
      associated with higher TB stigma among patients. All differences in mean stigma
      scores between index and referent levels of each factor were less than two
      points, except for incorrectly believing that TB increases the chance of getting
      AIDS (mean difference of 2.16; 95% CI: 1.38, 2.94) and knowing someone who died
      from TB (mean difference of 2.59; 95% CI: 0.96, 4.22). CONCLUSION: These results
      suggest that approaches addressing the dual TB/HIV epidemic may be needed to
      combat TB stigma and that simply correcting misconceptions about TB may have
      limited effects.

PMID- 21878103
TI  - Elective surgical referral guidelines--background educational material or
      essential shared decision making tool? A survey of GPs' in England.
AB  - BACKGROUND: To investigate general practitioners' (GPs') attitudes to guidelines
      for elective surgical referral in England. To understand their use of guidelines,
      and attitudes to shared decision making in the referral decision. METHODS: A
      questionnaire was developed which investigated attitudes to and use of
      guidelines. It was given to a stratified random sample 30% (n = 310) drawn from
      GP lists of 10 English health districts (primary care trusts (PCTs)). GPs were
      invited to respond online, by telephone, fax or post. Data were analysed using
      descriptive statistics and backwards stepwise logistic regression. RESULTS:
      Responses were representative of GPs in England, but (despite up to 6 contacts
      per non-responder) the overall response rate was 41.6% (n = 129; with the range
      across PCTs of 25-61%). Most responding GPs indicated support for referral
      guidelines but 18% reported that they had never used them. Less than three per
      cent reported use for most or all referral decisions. The odds of using
      guidelines decreased with increasing age, with a ten year increase in age
      associated with halving odds of use (OR = 0.53, 95%CI = 0.29-0.90). Over 50% of
      GPs wanted good access to electronic guidelines with expert information and
      advice on guideline availability. Almost all (>89%) GPs agreed with sharing
      referral decisions with patients. Female doctors (OR = 5.2, 95%CI: 1.02-26.3)
      were more likely to agree with this than male GPs as were those working in larger
      compared to small or single handed practices (OR = 5.3, 95%CI: 1.4-19.9).
      CONCLUSIONS: This group of responding GPs was supportive of guidelines but used
      them in different ways. Referral guidelines should have an educational component
      for background reading; include key messages for internalisation and application;
      and incorporate mechanisms to facilitate accessibility and appropriate shared
      decision making with patients.

PMID- 21878104
TI  - A longitudinal qualitative study examining the factors impacting on the ability
      of persons with T1DM to assimilate the Dose Adjustment for Normal Eating (DAFNE)
      principles into daily living and how these factors change over time.
AB  - BACKGROUND: The literature reveals that structured education programmes, such as
      DAFNE, result in many positive outcomes for people with Type 1 diabetes including
      a decrease in HbA1c levels and reductions in hypoglycaemia. While there is
      evidence that some of these outcomes are maintained we do not know at present
      what factors are most important over time. The study aim was to identify the key
      factors impacting on persons with Type 1 diabetes ability to assimilate the Dose
      Adjustment For Normal Eating (DAFNE) DAFNE principles into their daily lives and
      how these factors change over time. METHODS: This is a longitudinal descriptive
      qualitative study. Interviews were undertaken with 40 participants who had
      attended DAFNE in one of 5 study sites across the Island of Ireland, at 6 weeks,
      6 and 12 months after completion of the programme. The interviews lasted from 30
      to 60 minutes and were transcribed verbatim. Data were analysed in three ways, a
      within time analysis, a cross sectional analysis for each participant and a
      thematic analysis which focused on examining changes over time RESULTS: Four
      themes that influenced participants' ability to assimilate DAFNE into their daily
      lives over time were identified. These were: embedded knowledge, continued
      responsive support, enduring motivation and being empowered. Support at the 6
      month period was found to be crucial to continued motivation. CONCLUSIONS:
      Understanding the factors that influence people's ability to assimilate DAFNE
      principles over time into their daily lives can help health professionals give
      focused responsive support that helps people with diabetes become more empowered.
      Understanding that continued support matters, particularly around 6 months, is
      important as health professionals can influence good management by providing
      appropriate support and enhancing motivation. TRIAL REGISTRATION: ISRCTN79759174.

PMID- 21878105
TI  - CloVR: a virtual machine for automated and portable sequence analysis from the
      desktop using cloud computing.
AB  - BACKGROUND: Next-generation sequencing technologies have decentralized sequence
      acquisition, increasing the demand for new bioinformatics tools that are easy to
      use, portable across multiple platforms, and scalable for high-throughput
      applications. Cloud computing platforms provide on-demand access to computing
      infrastructure over the Internet and can be used in combination with custom built
      virtual machines to distribute pre-packaged with pre-configured software.
      RESULTS: We describe the Cloud Virtual Resource, CloVR, a new desktop application
      for push-button automated sequence analysis that can utilize cloud computing
      resources. CloVR is implemented as a single portable virtual machine (VM) that
      provides several automated analysis pipelines for microbial genomics, including
      16S, whole genome and metagenome sequence analysis. The CloVR VM runs on a
      personal computer, utilizes local computer resources and requires minimal
      installation, addressing key challenges in deploying bioinformatics workflows. In
      addition CloVR supports use of remote cloud computing resources to improve
      performance for large-scale sequence processing. In a case study, we demonstrate
      the use of CloVR to automatically process next-generation sequencing data on
      multiple cloud computing platforms. CONCLUSION: The CloVR VM and associated
      architecture lowers the barrier of entry for utilizing complex analysis protocols
      on both local single- and multi-core computers and cloud systems for high
      throughput data processing.

PMID- 21878107
TI  - Air ambulance flights in northern Norway 2002-2008. Increased number of secondary
      fixed wing (FW) operations and more use of rotor wing (RW) transports.
AB  - BACKGROUND: Air ambulance service in Norway has been upgraded during the last
      years. European regulations concerning pilots' working time and new treatment
      guidelines/strategies have called for more resources. AIMS: The objective was to
      describe and analyse the two supplementary air ambulance [fixed wing (FW) and
      rotor wing (RW)] alternatives' activity during the study period (2002-2008).
      Furthermore we aimed to compare our findings with reports from other north
      European regions. METHODS: A retrospective analysis. The air ambulance fleet's
      activity according to the electronic patient record database of
      "Luftambulansetjenesten ANS" (LABAS) was analysed. The subject was the fleet's
      operations in northern Norway, logistics, and patients handled. Type of flight,
      distances, frequency, and patients served were the main outcome measures.
      RESULTS: A significant increase (45%) in the use of RW and a shift in FW
      operations (less primary and more secondary) were revealed. The shift in FW
      operations reflected the centralisation of several health care services [i.e.
      percutaneous cardiac intervention (PCI), trauma, and cancer surgery] during the
      study period. Cardiovascular disease (CVD) and injuries were the main diagnoses
      and constituted half of all operations. CVD was the most common cause of FW
      operations and injuries of the RW ones. The number of air ambulance operations
      was 16 per 1,000 inhabitants. This was more frequent than in other north European
      regions. CONCLUSIONS: The use of air ambulances and especially RW was
      significantly increased during the study period. The change in secondary FW
      operations reflected centralisation of medical care. When health care services
      are centralised, air ambulance services must be adjusted to the new settings.

PMID- 21878106
TI  - Soluble amyloid precursor protein: a novel proliferation factor of adult
      progenitor cells of ectodermal and mesodermal origin.
AB  - INTRODUCTION: Soluble amyloid precursor protein alpha (sAPPalpha) is a proteolyte
      of APP cleavage by alpha-secretase. The significance of the cleavage and the
      physiological role of sAPPalpha are unknown. A crystal structure of a region of
      the amino terminal of sAPPalpha reveals a domain that is similar to cysteine-rich
      growth factors. While a previous study implicates sAPPalpha in the regulation of
      neural progenitor cell proliferation in the subventricular zone of adult mice,
      the ubiquitous expression of APP suggests that its role as a growth factor might
      be broader. METHODS: sAPPalpha and alpha-secretase activities were determined in
      neural progenitor cells (NPCs), mesenchymal stem cells (MSC) and human decidua
      parietalis placenta stem cells (hdPSC). Inhibition of alpha-secretase was
      achieved by treatment with the matrixmetalloproteinase inhibitor GM6001, and
      proliferation was determined using clonogenic and immunocytochemical analysis of
      cell-lineage markers. Recovery of proliferation was achieved by supplementing
      GM6001-treated cells with recombinant soluble APPalpha. Expression of APP and its
      cellular localization in the subventricular zone was determined by Western blot
      and immunohistochemical analyses of APP wild type and knockout tissue.
      Alterations in pERK and pAKT expression as a function of soluble APPalpha
      production and activity in NPCs were determined by Western blot analysis.
      RESULTS: Here we show that sAPPalpha is a proliferation factor of adult NPCs,
      MSCs and hdpPSC. Inhibition of alpha-secretase activity reduces proliferation of
      these stem cell populations in a dose-dependent manner. Stem cell proliferation
      can be recovered by the addition of sAPPalpha in a dose-dependent manner, but not
      of media depleted of sAPPalpha. Importantly, sAPPalpha operates independently of
      the prominent proliferation factors epidermal growth factor (EGF) and basic
      fibroblast growth factor (bFGF), but in association with ERK signaling and MAP
      kinase signaling pathways. Levels of sAPPalpha and putative alpha-secretase,
      ADAM10, are particularly high in the subventricular zone of adult mice,
      suggesting a role for sAPPalpha in regulation of NPCs in this microenvironment.
      CONCLUSIONS: These results determine a physiological function for sAPPalpha and
      identify a new proliferation factor of progenitor cells of ectodermal and
      mesodermal origin. Further, our studies elucidate a potential pathway for
      sAPPalpha signaling through MAP kinase activation.

PMID- 21878108
TI  - Impact of aprotinin and renal function on mortality: a retrospective single
      center analysis.
AB  - BACKGROUND: An estimated up to 7% of high-risk cardiac surgery patients return to
      the operating room for bleeding. Aprotinin was used extensively as an
      antifibrinolytic agent in cardiac surgery patients for over 15 years and it
      showed efficacy in reducing bleeding. Aprotinin was removed from the market by
      the U.S. Food and Drug Administration after a large prospective, randomized
      clinical trial documented an increased mortality risk associated with the drug.
      Further debate arose when a meta-analysis of 211 randomized controlled trials
      showed no risk of renal failure or death associated with aprotinin. However, only
      patients with normal kidney function have been studied. METHODS: In this study,
      we look at a single center clinical trial using patients with varying degrees of
      baseline kidney function to answer the question: Does aprotinin increase odds of
      death given varying levels of preoperative kidney dysfunction? RESULTS: Based on
      our model, aprotinin use was associated with a 3.8-fold increase in odds of death
      one year later compared to no aprotinin use with p-value = 0.0018, regardless of
      level of preoperative kidney dysfunction after adjusting for other perioperative
      variables. CONCLUSIONS: Lessons learned from our experience using aprotinin in
      the perioperative setting as an antifibrinolytic during open cardiac surgery
      should guide us in testing future antifibrinolytic drugs for not only efficacy of
      preventing bleeding, but for overall safety to the whole organism using long-term
      clinical outcome studies, including those with varying degree of baseline kidney
      function.

PMID- 21878109
TI  - The RICORDO approach to semantic interoperability for biomedical data and models:
      strategy, standards and solutions.
AB  - BACKGROUND: The practice and research of medicine generates considerable
      quantities of data and model resources (DMRs). Although in principle biomedical
      resources are re-usable, in practice few can currently be shared. In particular,
      the clinical communities in physiology and pharmacology research, as well as
      medical education, (i.e. PPME communities) are facing considerable operational
      and technical obstacles in sharing data and models. FINDINGS: We outline the
      efforts of the PPME communities to achieve automated semantic interoperability
      for clinical resource documentation in collaboration with the RICORDO project.
      Current community practices in resource documentation and knowledge management
      are overviewed. Furthermore, requirements and improvements sought by the PPME
      communities to current documentation practices are discussed. The RICORDO plan
      and effort in creating a representational framework and associated open software
      toolkit for the automated management of PPME metadata resources is also
      described. CONCLUSIONS: RICORDO is providing the PPME community with tools to
      effect, share and reason over clinical resource annotations. This work is
      contributing to the semantic interoperability of DMRs through ontology-based
      annotation by (i) supporting more effective navigation and re-use of clinical
      DMRs, as well as (ii) sustaining interoperability operations based on the
      criterion of biological similarity. Operations facilitated by RICORDO will range
      from automated dataset matching to model merging and managing complex simulation
      workflows. In effect, RICORDO is contributing to community standards for resource
      sharing and interoperability.

PMID- 21878111
TI  - Home care in Europe: a systematic literature review.
AB  - BACKGROUND: Health and social services provided at home are becoming increasingly
      important. Hence, there is a need for information on home care in Europe. The
      objective of this literature review was to respond to this need by systematically
      describing what has been reported on home care in Europe in the scientific
      literature over the past decade. METHODS: A systematic literature search was
      performed for papers on home care published in English, using the following data
      bases: Cinahl, the Cochrane Library, Embase, Medline, PsycINFO, Sociological
      Abstracts, Social Services Abstracts, and Social Care Online. Studies were only
      included if they complied with the definition of home care, were published
      between January 1998 and October 2009, and dealt with at least one of the 31
      specified countries. Clinical interventions, instrument developments, local
      projects and reviews were excluded. The data extracted included: the
      characteristics of the study and aspects of home care 'policy & regulation',
      'financing', 'organisation & service delivery', and 'clients & informal carers'.
      RESULTS: Seventy-four out of 5,133 potentially relevant studies met the inclusion
      criteria, providing information on 18 countries. Many focused on the
      characteristics of home care recipients and on the organisation of home care.
      Geographical inequalities, market forces, quality and integration of services
      were also among the issues frequently discussed. CONCLUSIONS: Home care systems
      appeared to differ both between and within countries. The papers included,
      however, provided only a limited picture of home care. Many studies only focused
      on one aspect of the home care system and international comparative studies were
      rare. Furthermore, little information emerged on home care financing and on home
      care in general in Eastern Europe. This review clearly shows the need for more
      scientific publications on home care, especially studies comparing countries. A
      comprehensive and more complete insight into the state of home care in Europe
      requires the gathering of information using a uniform framework and methodology.

PMID- 21878110
TI  - Two new Rett syndrome families and review of the literature: expanding the
      knowledge of MECP2 frameshift mutations.
AB  - BACKGROUND: Rett syndrome (RTT) is an X-linked dominant neurodevelopmental
      disorder, which is usually caused by de novo mutations in the MECP2 gene. More
      than 70% of the disease causing MECP2 mutations are eight recurrent C to T
      transitions, which almost exclusively arise on the paternally derived X
      chromosome. About 10% of the RTT cases have a C-terminal frameshift deletion in
      MECP2. Only few RTT families with a segregating MECP2 mutation, which affects
      female carriers with a phenotype of mental retardation or RTT, have been reported
      in the literature. In this study we describe two new RTT families with three and
      four individuals, respectively, and review the literature comparing the type of
      mutations and phenotypes observed in RTT families with those observed in sporadic
      cases. Based on these observations we also investigated origin of mutation
      segregation to further improve genetic counselling. METHODS: MECP2 mutations were
      identified by direct sequencing. XCI studies were performed using the X-linked
      androgen receptor (AR) locus. The parental origin of de novo MECP2 frameshift
      mutations was investigated using intronic SNPs. RESULTS: In both families a C
      terminal frameshift mutation segregates. Clinical features of the mutation
      carriers vary from classical RTT to mild mental retardation. XCI profiles of the
      female carriers correlate to their respective geno-/phenotypes. The majority of
      the de novo frameshift mutations occur on the paternally derived X chromosome
      (7/9 cases), without a paternal age effect. CONCLUSIONS: The present study
      suggests a correlation between the intrafamilial phenotypic differences observed
      in RTT families and their respective XCI pattern in blood, in contrast to
      sporadic RTT cases where a similar correlation has not been demonstrated.
      Furthermore, we found de novo MECP2 frameshift mutations frequently to be of
      paternal origin, although not with the same high paternal occurrence as in
      sporadic cases with C to T transitions. This suggests further investigations of
      more families. This study emphasizes the need for thorough genetic counselling of
      families with a newly diagnosed RTT patient.

PMID- 21878112
TI  - The changing trends in tobacco smoking for young Arab women; narghile, an old
      habit with a liberal attitude.
AB  - Narghile smoking by young females is becoming more acceptable than cigarettes in
      the conservative societies of Arab countries. Lack of social constraints on
      narghile smoking has resulted in an increased prevalence of narghile smoking
      among young Arab females and an earlier age of onset of this habit when compared
      to cigarette smoking.Documented health hazards of narghile smoking including
      pulmonary, cardiovascular and neoplastic ailments are consequently expected to
      affect this vulnerable sector of the population together with their offspring. In
      this commentary, we shed some light on the changing trend of tobacco use among
      young Arabic women as shown by an increasing number of studies investigating
      habits of tobacco use in young people.

PMID- 21878114
TI  - The method of Katharina Schroth - history, principles and current development.

PMID- 21878113
TI  - Ambient PM exposure and DNA methylation in tumor suppressor genes: a cross
      sectional study.
AB  - Exposure to ambient air particles matter (PM) has been associated with increased
      risk of lung cancer. Aberrant tumor suppressor gene promoter methylation has
      emerged as a promising biomarker for cancers, including lung cancer. Whether
      exposure to PM is associated with peripheral blood leukocyte (PBL) DNA
      methylation in tumor suppressor genes has not been evaluated. In 63 male healthy
      steel workers with well-characterized exposure to metal-rich particles nearby
      Brescia, Italy, we evaluated whether exposure to PM and metal components was
      associated with PBL DNA methylation in 4 tumor suppressor genes (i.e., APC, p16,
      p53 and RASSF1A). Blood samples were obtained on the 1st (baseline) and 4th day
      (post-exposure) of the same work week and DNA methylation was measured using
      pyrosequencing. A linear mixed model was used to examine the correlations of the
      exposure with promoter methylation levels. Mean promoter DNA methylation levels
      of APC or p16 were significantly higher in post-exposure samples compared to that
      in baseline samples (p-values = 0.005 for APC, and p-value = 0.006 for p16). By
      contrast, the mean levels of p53 or RASSF1A promoter methylation was decreased in
      post-exposure samples compared to that in baseline samples (p-value = 0.015 for
      p53; and p-value < 0.001 for RASSF1A). In post-exposure samples, APC methylation
      was positively associated with PM10 (beta = 0.27, 95% CI: 0.13-0.40), and PM1
      (beta = 0.23, 95% CI: 0.09-0.38). In summary, ambient PM exposure was associated
      with PBL DNA methylation levels of tumor suppressor genes of APC, p16, p53 and
      RASSF1A, suggesting that such methylation alterations may reflect processes
      related to PM-induced lung carcinogenesis.

PMID- 21878115
TI  - Profiles of and practices in crisis resolution and home treatment teams in
      Norway: a longitudinal survey study.
AB  - BACKGROUND: Crisis resolution and home treatment (CRHT) is one of the more recent
      modes of delivering acute mental health care in the community. The objective of
      the study was to describe the standardizations and variations in the CRHT teams
      in Norway in order to gain knowledge regarding the structures and processes of
      CRHT teams. METHODS: A longitudinal survey of five CRHT teams in Norway was
      carried out for a period of 18 months with two sets of questionnaires-one for
      CRHT team profiles for a bi-yearly survey and the other for services and
      practices of CRHT teams for a monthly survey. RESULTS: The five CRHT teams were
      configured by a set of common basic characteristics in their operations, while at
      the same time were variant in several areas of the teams' structures and
      processes. Significant differences among the teams were evident in terms of the
      structural aspects such as service locality, staffing and team make-up, caseload,
      service hours, and travel time, and the process aspects such as the number of
      referrals received, referral source, admission, service duration, and discharge
      destination. These variations are reflected upon the perspectives regarding the
      nature of mental health crisis, the conflicting policies in mental health
      services, and the nature of home-based mental health care. CONCLUSIONS: The
      diversity in the way CRHT teams are established and operate needs to be examined
      further in order to understand the reasons for such variations and their impact
      on the quality of services to service users and in relation to the total mental
      health service system in a community.

PMID- 21878116
TI  - TDP-43 knockdown impairs neurite outgrowth dependent on its target histone
      deacetylase 6.
AB  - BACKGROUND: Trans-activation response element (TAR) DNA binding protein of 43kDa
      (TDP-43) is causally related to the neurodegenerative diseases frontotemporal
      dementia and amyotrophic lateral sclerosis being the hallmark protein in the
      disease-characteristic neuropathological lesions and via genetic linkage. Histone
      deacetylase 6 (HDAC6) is an established target of the RNA-binding protein TDP-43.
      HDAC6 is an unusual cytosolic deacetylase enzyme, central for a variety of
      pivotal cellular functions including aggregating protein turnover, microtubular
      dynamics and filopodia formation. All these functions are important in the
      context of neurodegenerative proteinopathies involving TDP-43. We have previously
      shown in a human embryonic kidney cell line that TDP-43 knockdown significantly
      impairs the removal of a toxic, aggregating polyQ ataxin-3 fusion protein in an
      HDAC6-dependent manner. Here we investigated the influence of TDP-43 and its
      target HDAC6 on neurite outgrowth. RESULTS: Human neuroblastoma SH-SY5Y cells
      with stably silenced TDP-43 showed a significant reduction of neurite outgrowth
      induced by retinoic acid and brain-derived neurotrophic factor. Re-transfection
      with TDP-43 as well as HDAC6 rescued retinoic acid-induced neurite outgrowth. In
      addition, we show that silencing of HDAC6 alone is sufficient to reduce neurite
      outgrowth of in vitro differentiated SH-SY5Y cells. CONCLUSIONS: TDP-43
      deficiency leads to impairment of neurite growth in an HDAC6-dependent manner,
      thereby contributing to neurodegenerative events in TDP-43 diseases.

PMID- 21878118
TI  - Angiofibroma of the spermatic cord: a case report and a review of the literature.
AB  - INTRODUCTION: Cellular angiofibroma is a benign vascular neoplasm that typically
      arises in the paratesticular region in men and is easily confused with inguinal
      or scrotal hernia. CASE PRESENTATION: We present a case of a cellular
      angiofibroma arising from the spermatic cord of a 74-year-old Caucasian man.
      Initially, the lesion was confused with a scrotal hernia, but imaging revealed a
      subcutaneous, inhomogeneous, but well-circumscribed lesion to the surrounding
      tissues with rich vasculature. Surgical resection of the lesion was performed.
      Histology revealed a benign tumor of vascular origin rich in fibroblasts.
      CONCLUSIONS: Angiofibroma can easily be confused with an inguinal hernia and
      should be differentiated from Schwann cell tumors, perineuromas, spindle-cell
      lipomas, aggressive angiomyxomas, angiomyofibroblastomas, solitary fibrous
      tumors, spindle-cell liposarcomas, and leiomyomas. A safe initial diagnosis is
      difficult because of its location, nature, and correlation with other structures
      of the area.

PMID- 21878117
TI  - Plasticity of photoreceptor-generating retinal progenitors revealed by prolonged
      retinoic acid exposure.
AB  - BACKGROUND: Retinoic acid (RA) is important for vertebrate eye morphogenesis and
      is a regulator of photoreceptor development in the retina. In the zebrafish, RA
      treatment of postmitotic photoreceptor precursors has been shown to promote the
      differentiation of rods and red-sensitive cones while inhibiting the
      differentiation of blue- and UV-sensitive cones. The roles played by RA and its
      receptors in modifying photoreceptor fate remain to be determined. RESULTS:
      Treatment of zebrafish embryos with RA, beginning at the time of retinal
      progenitor cell proliferation and prior to photoreceptor terminal mitosis,
      resulted in a significant alteration of rod and cone mosaic patterns, suggesting
      an increase in the production of rods at the expense of red cones. Quantitative
      pattern analyses documented increased density of rod photoreceptors and reduced
      local spacing between rod cells, suggesting rods were appearing in locations
      normally occupied by cone photoreceptors. Cone densities were correspondingly
      reduced and cone photoreceptor mosaics displayed expanded and less regular
      spacing. These results were consistent with replacement of approximately 25% of
      positions normally occupied by red-sensitive cones, with additional rods.
      Analysis of embryos from a RA-signaling reporter line determined that multiple
      retinal cell types, including mitotic cells and differentiating rods and cones,
      are capable of directly responding to RA. The RA receptors RXRgamma and RARalphab
      are expressed in patterns consistent with mediating the effects of RA on
      photoreceptors. Selective knockdown of RARalphab expression resulted in a
      reduction in endogenous RA signaling in the retina. Knockdown of RARalphab also
      caused a reduced production of rods that was not restored by simultaneous
      treatments with RA. CONCLUSIONS: These data suggest that developing retinal cells
      have a dynamic sensitivity to RA during retinal neurogenesis. In zebrafish RA may
      influence the rod vs. cone cell fate decision. The RARalphab receptor mediates
      the effects of endogenous, as well as exogenous RA, on rod development.

PMID- 21878119
TI  - Accidental finding of a toothpick in the porta hepatis during laparoscopic
      cholecystectomy: a case report.
AB  - INTRODUCTION: Unintentional ingestion of a toothpick is not an uncommon event.
      Often the ingested toothpicks spontaneously pass through the gut without
      sequelae. However, serious complications can happen when these sharp objects
      migrate through the gastrointestinal wall. CASE PRESENTATION: In the current
      report, we describe the case of a 37-year-old Caucasian woman with an incidental
      finding of a toothpick in the porta hepatis during laparoscopic cholecystectomy
      for symptomatic gall stones. CONCLUSION: Toothpick ingestion is not an uncommon
      event and can predispose patients to serious complications. In this particular
      case, the toothpick was only discovered at the time of unrelated surgery.
      Therefore, it was important during surgery to exclude any related or missed
      injury to the adjacent structures by this sharp object.

PMID- 21878120
TI  - Atomic force microscopy analysis of nanoparticles in non-ideal conditions.
AB  - Nanoparticles are often measured using atomic force microscopy or other scanning
      probe microscopy methods. For isolated nanoparticles on flat substrates, this is
      a relatively easy task. However, in real situations, we often need to analyze
      nanoparticles on rough substrates or nanoparticles that are not isolated. In this
      article, we present a simple model for realistic simulations of nanoparticle
      deposition and we employ this model for modeling nanoparticles on rough
      substrates. Different modeling conditions (coverage, relaxation after deposition)
      and convolution with different tip shapes are used to obtain a wide spectrum of
      virtual AFM nanoparticle images similar to those known from practice. Statistical
      parameters of nanoparticles are then analyzed using different data processing
      algorithms in order to show their systematic errors and to estimate uncertainties
      for atomic force microscopy analysis of nanoparticles under non-ideal conditions.
      It is shown that the elimination of user influence on the data processing
      algorithm is a key step for obtaining accurate results while analyzing
      nanoparticles measured in non-ideal conditions.

PMID- 21878121
TI  - Potential prognostic marker ubiquitin carboxyl-terminal hydrolase-L1 does not
      predict patient survival in non-small cell lung carcinoma.
AB  - BACKGROUND: Ubiquitin Carboxyl-Terminal Hydrolase-L1 (UCH-L1) is a
      deubiquitinating enzyme that is highly expressed throughout the central and
      peripheral nervous system and in cells of the diffuse neuroendocrine system.
      Aberrant function of UCH-L1 has been associated with neurological disorders such
      as Parkinson's disease and Alzheimer's disease. Moreover, UCH-L1 exhibits a
      variable expression pattern in cancer, acting either as a tumour suppressor or
      promoter, depending on the type of cancer. In non-small cell lung carcinoma
      primary tumour samples, UCH-L1 is highly expressed and is associated with an
      advanced tumour stage. This suggests UCH-L1 may be involved in oncogenic
      transformation and tumour invasion in NSCLC. However, the functional significance
      of UCH-L1 in the progression of NSCLC is unclear. The aim of this study was to
      investigate the role of UCH-L1 using NSCLC cell line models and to determine if
      it is clinically relevant as a prognostic marker for advanced stage disease.
      METHODS: UCH-L1 expression in NSCLC cell lines H838 and H157 was modulated by
      siRNA-knockdown, and the phenotypic changes were assessed by flow cytometry,
      haematoxylin & eosin (H&E) staining and poly (ADP-ribose) polymerase (PARP)
      cleavage. Metastatic potential was measured by the presence of phosphorylated
      myosin light chain (MLC2). Tumour microarrays were examined immunohistochemically
      for UCH-L1 expression. Kaplan-Meier curves were generated using UCH-L1 expression
      levels and patient survival data extracted from Gene Expression Omnibus data
      files. RESULTS: Expression of UCH-L1 was decreased by siRNA in both cell lines,
      resulting in increased cell death in H838 adenocarcinoma cells but not in the
      H157 squamous cell line. However, metastatic potential was reduced in H157 cells.
      Immunohistochemical staining of UCH-L1 in patient tumours confirmed it was
      preferentially expressed in squamous cell carcinoma rather than adenocarcinoma.
      However the Kaplan-Meier curves generated showed no correlation between UCH-L1
      expression levels and patient outcome. CONCLUSIONS: Although UCH-L1 appears to be
      involved in carcinogenic processes in NSCLC cell lines, the absence of
      correlation with patient survival indicates that caution is required in the use
      of UCH-L1 as a potential prognostic marker for advanced stage and metastasis in
      lung carcinoma.

PMID- 21878122
TI  - Introduction of organised mammography screening in Tyrol: results following first
      year of complete rollout.
AB  - BACKGROUND: In Tyrol, Austria, the existing system of spontaneous mammography
      screening was switched in 2007 to an organised program by smoothly changing the
      established framework. This process followed most EU recommendations for
      organised mammography screening with the following exceptions: women aged 40-49
      are part of the target population, screening is offered annually to the age group
      40-59, breast ultrasound is available as an additional diagnostic tool, and
      double reading has not yet been implemented. After a pilot phase the program was
      rolled out to all of Tyrol in June 2008. The aim of this study was to analyse the
      performance of the organised screening system by comparing quality indices and
      recommended levels given in the well-established EU guidelines. METHODS: Working
      from the results of the pilot phase, we extended the organised mammography system
      to all counties in Tyrol. All women living in Tyrol and covered by compulsory
      social insurance were invited for a mammography, in the age group 40-59 annually
      and in the age group 60-69 biennially. Screening mammography was offered mainly
      by radiologists in private practice, with further assessment performed at
      hospitals. Using the screening database, all well-established performance
      indicators were analysed and compared with accepted/desired levels as per the EU
      guidelines. RESULTS: From June 2008 to May 2009, 120,440 women were invited. Per
      1000 mammograms, 14 women were recalled for further assessment, nine underwent
      biopsy and four cancer cases were detected. Of invasive breast cancer cases,
      32.3% and 68.4% were <= 10 mm and <= 15 mm in size, respectively, and 79.2% were
      node-negative. The positive predictive value for further assessment and for
      biopsy was 25.9% and 39.9%, respectively. Estimated two-year participation rate
      was 57.0%. In total, 14 interval cancer cases were detected during one year of
      follow-up; this is 18.4% of the background incidence rate. CONCLUSIONS: In Tyrol,
      Austria, an organised mammography screening program was implemented in a smooth
      transition from an existing spontaneous screening system and was completely
      rolled out within a short time. The high level of performance already seen in the
      pilot phase was maintained after rollout, and improvements resulting from the
      pilot phase were affirmed after one year of complete rollout.

PMID- 21878123
TI  - Vocation and avocation: leisure activities correlate with professional
      engagement, but not burnout, in a cross-sectional survey of UK doctors.
AB  - BACKGROUND: Sir William Osler suggested in 1899 that avocations (leisure
      activities) in doctors are related to an increased sense of vocation
      (professional engagement) and a decreased level of burnout. This study evaluated
      those claims in a large group of doctors practicing in the UK while taking into
      account a wide range of background variables. METHODS: A follow-up questionnaire
      was sent to 4,457 UK-qualified doctors who had been included in four previous
      studies of medical school selection and training, beginning in 1980, 1985, 1990
      and 1989/1991. A total of 2,845 (63.8%) doctors returned the questionnaire.
      Questions particularly asked about work engagement, satisfaction with medicine as
      a career, and personal achievement (Vocation/engagement), stress, emotional
      exhaustion, and depersonalization (BurnedOut), and 29 different leisure
      activities (Avocation/Leisure), as well as questions on personality, empathy,
      work experience, and demography. RESULTS: Doctors reporting more
      Avocation/Leisure activities tended to be women, to have older children, to be
      less surface-rational, more extravert, more open to experience, less agreeable,
      and to fantasize more. Doctors who were more BurnedOut tended to be men, to be
      more sleep-deprived, to report a greater workload and less choice and
      independence in their work, to have higher neuroticism, lower extraversion and
      lower agreeableness scores, and to have lower self-esteem. In contrast, doctors
      with a greater sense of Vocation/engagement, tended to see more patients, to have
      greater choice and independence at work, to have a deep approach to work, to have
      a more supportive-receptive work environment, to be more extravert and more
      conscientious, and to report greater self-esteem.Avocation/Leisure activities
      correlated significantly with Vocation/engagement, even after taking into account
      25 background variables describing demography, work, and personality, whereas
      BurnedOut showed no significant correlation with Avocation/Leisure activities.
      Popular Culture and High Culture did not differ in their influence on
      Vocation/engagement, although there was a suggestion that Depersonalization was
      correlated with more interest in Popular Culture and less interest in High
      Culture. CONCLUSION: In this cross-sectional study there is evidence, even after
      taking into account a wide range of individual difference measures, that doctors
      with greater Avocation/Leisure activities also have a greater sense of
      Vocation/Engagement. In contrast, being BurnedOut did not relate to
      Avocation/Leisure activities (but did relate to many other measures). Osler was
      probably correct in recommending to doctors that, 'While medicine is to be your
      vocation, or calling, see to it that you also have an avocation'.

PMID- 21878124
TI  - Vaccine-induced antibodies linked to bovine neonatal pancytopenia (BNP) recognize
      cattle major histocompatibility complex class I (MHC I).
AB  - A mysterious disease affecting calves, named bovine neonatal pancytopenia (BNP),
      emerged in 2007 in several European countries. Epidemiological studies revealed a
      connection between BNP and vaccination with an inactivated vaccine against bovine
      virus diarrhea (BVD). Alloantibodies reacting with blood leukocytes of calves
      were detected in serum and colostrum of dams, which have given birth to calves
      affected by BNP. To understand the linkage between vaccination and the
      development of alloantibodies, we determined the antigens reacting with these
      alloantibodies. Immunoprecipitation of surface proteins from bovine leukocytes
      and kidney cells using sera from dams with a confirmed case of BNP in their
      gestation history reacted with two dominant protein species of 44 and 12 kDa.
      These proteins were not detected by sera from dams, free of BVDV and not
      vaccinated against BVD, and from sera of animals vaccinated with a different
      inactivated BVD vaccine. The 44 kDa protein was identified by mass spectrometry
      analysis as MHC I, the other as beta-2-microglobulin. The presence of major
      histocompatibility complex class I (MHC I) in the vaccine was confirmed by
      Western blot using a MHC I specific monoclonal antibody. A model of BNP
      pathogenesis is proposed.

PMID- 21878125
TI  - Wallerian degeneration: the innate-immune response to traumatic nerve injury.
AB  - Traumatic injury to peripheral nerves results in the loss of neural functions.
      Recovery by regeneration depends on the cellular and molecular events of
      Wallerian degeneration that injury induces distal to the lesion site, the domain
      through which severed axons regenerate back to their target tissues. Innate
      immunity is central to Wallerian degeneration since innate-immune cells,
      functions and molecules that are produced by immune and non-immune cells are
      involved. The innate-immune response helps to turn the peripheral nerve tissue
      into an environment that supports regeneration by removing inhibitory myelin and
      by upregulating neurotrophic properties. The characteristics of an efficient
      innate-immune response are rapid onset and conclusion, and the orchestrated
      interplay between Schwann cells, fibroblasts, macrophages, endothelial cells, and
      molecules they produce. Wallerian degeneration serves as a prelude for successful
      repair when these requirements are met. In contrast, functional recovery is poor
      when injury fails to produce the efficient innate-immune response of Wallerian
      degeneration.

PMID- 21878127
TI  - The impact of modern migrations on present-day multi-ethnic Argentina as recorded
      on the mitochondrial DNA genome.
AB  - BACKGROUND: The genetic background of Argentineans is a mosaic of different
      continental ancestries. From colonial to present times, the genetic contribution
      of Europeans and sub-Saharan Africans has superposed to or replaced the
      indigenous genetic 'stratum'. A sample of 384 individuals representing different
      Argentinean provinces was collected and genotyped for the first and the second
      mitochondrial DNA (mtDNA) hypervariable regions, and selectively genotyped for
      mtDNA SNPs. This data was analyzed together with additional 440 profiles from
      rural and urban populations plus 304 from Native American Argentineans, all
      available from the literature. A worldwide database was used for phylogeographic
      inferences, inter-population comparisons, and admixture analysis. Samples
      identified as belonging to hg (hg) H2a5 were sequenced for the entire mtDNA
      genome. RESULTS: Phylogenetic and admixture analyses indicate that only half of
      the Native American component in urban Argentineans might be attributed to the
      legacy of extinct ancestral Argentineans and that the Spanish genetic
      contribution is slightly higher than the Italian one. Entire H2a5 genomes linked
      these Argentinean mtDNAs to the Basque Country and improved the phylogeny of this
      Basque autochthonous clade. The fingerprint of African slaves in urban
      Argentinean mtDNAs was low and it can be phylogeographically attributed
      predominantly to western African. The European component is significantly more
      prevalent in the Buenos Aires province, the main gate of entrance for Atlantic
      immigration to Argentina, while the Native American component is larger in North
      and South Argentina. AMOVA, Principal Component Analysis and hgs/haplotype
      patterns in Argentina revealed an important level of genetic sub-structure in the
      country. CONCLUSIONS: Studies aimed to compare mtDNA frequency profiles from
      different Argentinean geographical regions (e.g., forensic and case-control
      studies) should take into account the important genetic heterogeneity of the
      country in order to prevent false positive claims of association in disease
      studies or inadequate evaluation of forensic evidence.

PMID- 21878126
TI  - Wallerian degeneration: gaining perspective on inflammatory events after
      peripheral nerve injury.
AB  - In this review, we first provide a brief historical perspective, discussing how
      peripheral nerve injury (PNI) may have caused World War I. We then consider the
      initiation, progression, and resolution of the cellular inflammatory response
      after PNI, before comparing the PNI inflammatory response with that induced by
      spinal cord injury (SCI).In contrast with central nervous system (CNS) axons,
      those in the periphery have the remarkable ability to regenerate after injury.
      Nevertheless, peripheral nervous system (PNS) axon regrowth is hampered by nerve
      gaps created by injury. In addition, the growth-supportive milieu of PNS axons is
      not sustained over time, precluding long-distance regeneration. Therefore,
      studying PNI could be instructive for both improving PNS regeneration and
      recovery after CNS injury. In addition to requiring a robust regenerative
      response from the injured neuron itself, successful axon regeneration is
      dependent on the coordinated efforts of non-neuronal cells which release
      extracellular matrix molecules, cytokines, and growth factors that support axon
      regrowth. The inflammatory response is initiated by axonal disintegration in the
      distal nerve stump: this causes blood-nerve barrier permeabilization and
      activates nearby Schwann cells and resident macrophages via receptors sensitive
      to tissue damage. Denervated Schwann cells respond to injury by shedding myelin,
      proliferating, phagocytosing debris, and releasing cytokines that recruit blood
      borne monocytes/macrophages. Macrophages take over the bulk of phagocytosis
      within days of PNI, before exiting the nerve by the circulation once
      remyelination has occurred. The efficacy of the PNS inflammatory response
      (although transient) stands in stark contrast with that of the CNS, where the
      response of nearby cells is associated with inhibitory scar formation,
      quiescence, and degeneration/apoptosis. Rather than efficiently removing debris
      before resolving the inflammatory response as in other tissues, macrophages
      infiltrating the CNS exacerbate cell death and damage by releasing toxic pro
      inflammatory mediators over an extended period of time. Future research will help
      determine how to manipulate PNS and CNS inflammatory responses in order to
      improve tissue repair and functional recovery.

PMID- 21878128
TI  - HPV vaccine decision making in pediatric primary care: a semi-structured
      interview study.
AB  - BACKGROUND: Despite national recommendations, as of 2009 human papillomavirus
      (HPV) vaccination rates were low with < 30% of adolescent girls fully vaccinated.
      Research on barriers to vaccination has focused separately on parents,
      adolescents, or clinicians and not on the decision making process among all
      participants at the point of care. By incorporating three distinct perspectives,
      we sought to generate hypotheses to inform interventions to increase vaccine
      receipt. METHODS: Between March and June, 2010, we conducted qualitative
      interviews with 20 adolescent-mother-clinician triads (60 individual interviews)
      directly after a preventive visit with the initial HPV vaccine due. Interviews
      followed a guide based on published HPV literature, involved 9 practices, and
      continued until saturation of the primary themes was achieved. Purposive sampling
      balanced adolescent ages and practice type (urban resident teaching versus non
      teaching). Using a modified grounded theory approach, we analyzed data with
      NVivo8 software both within and across triads to generate primary themes.
      RESULTS: The study population was comprised of 20 mothers (12 Black, 9 < high
      school diploma), 20 adolescents (ten 11-12 years old), and 20 clinicians (16
      female). Nine adolescents received the HPV vaccine at the visit, eight of whom
      were African American. Among the 11 not vaccinated, all either concurrently
      received or were already up-to-date on Tdap and MCV4. We did not observe
      systematic patterns of vaccine acceptance or refusal based on adolescent age or
      years of clinician experience. We identified 3 themes: (1) Parents delayed,
      rather than refused vaccination, and when they expressed reluctance, clinicians
      were hesitant to engage them in discussion. (2) Clinicians used one of two
      strategies to present the HPV vaccine, either presenting it as a routine vaccine
      with no additional information or presenting it as optional and highlighting
      risks and benefits. (3) Teens considered themselves passive participants in
      decision making, even when parents and clinicians reported including them in the
      process. CONCLUSIONS: Programs to improve HPV vaccine delivery in primary care
      should focus on promoting effective parent-clinician communication. Research is
      needed to evaluate strategies to help clinicians engage reluctant parents and
      passive teens in discussion and measure the impact of distinct clinician decision
      making approaches on HPV vaccine delivery.

PMID- 21878129
TI  - Clinical correlation of nonalcoholic fatty liver disease in a Chinese taxi
      drivers population in Taiwan: Experience at a teaching hospital.
AB  - BACKGROUND: To explore any gender-related differences in the prevalence of
      conditions-associated with non-alcoholic fatty liver disease (NAFLD) among
      Taiwanese taxi drivers in Taipei, Taiwan. METHODS: We studied 1635 healthy taxi
      drivers (1541 males and 94 females) who volunteered for physical check-ups in
      2006. Blood samples and ultrasound fatty liver sonography results were collected.
      RESULTS: The prevalence of NAFLD was 66.4% and revealed no statistically
      significant decrease with increasing age (p = 0.58). Males exhibited a greater
      prevalence of NAFLD than did females (67.5% vs 47.9%, p < 0.0001). Gender-related
      differences for associated factors were found. For males, hypertension,
      hyperuricemia, higher AST, higher ALT, hypertriglyceridemia, and higher fasting
      plasma glucose were significantly related to NAFLD. These conditions were not
      sigfinicantly related to NAFLD in females. CONCLUSION: Several gender-related
      differences were noted for NAFLD among Taiwanese taxi drivers.

PMID- 21878131
TI  - Ten steps or climbing a mountain: a study of Australian health professionals'
      perceptions of implementing the baby friendly health initiative to protect,
      promote and support breastfeeding.
AB  - BACKGROUND: The Baby Friendly Hospital (Health) Initiative (BFHI) is a global
      initiative aimed at protecting, promoting and supporting breastfeeding and is
      based on the ten steps to successful breastfeeding. Worldwide, over 20,000 health
      facilities have attained BFHI accreditation but only 77 Australian hospitals
      (approximately 23%) have received accreditation. Few studies have investigated
      the factors that facilitate or hinder implementation of BFHI but it is
      acknowledged this is a major undertaking requiring strategic planning and change
      management throughout an institution. This paper examines the perceptions of BFHI
      held by midwives and nurses working in one Area Health Service in NSW, Australia.
      METHODS: The study used an interpretive, qualitative approach. A total of 132
      health professionals, working across four maternity units, two neonatal intensive
      care units and related community services, participated in 10 focus groups. Data
      were analysed using thematic analysis. RESULTS: Three main themes were
      identified: 'Belief and Commitment'; 'Interpreting BFHI' and 'Climbing a
      Mountain'. Participants considered the BFHI implementation a high priority; an
      essential set of practices that would have positive benefits for babies and
      mothers both locally and globally as well as for health professionals. It was
      considered achievable but would take commitment and hard work to overcome the
      numerous challenges including a number of organisational constraints. There were,
      however, differing interpretations of what was required to attain BFHI
      accreditation with the potential that misinterpretation could hinder
      implementation. A model described by Greenhalgh and colleagues on adoption of
      innovation is drawn on to interpret the findings. CONCLUSION: Despite strong
      support for BFHI, the principles of this global strategy are interpreted
      differently by health professionals and further education and accurate
      information is required. It may be that the current processes used to disseminate
      and implement BFHI need to be reviewed. The findings suggest that there is a
      contradiction between the broad philosophical stance and best practice approach
      of this global strategy and the tendency for health professionals to focus on the
      ten steps as a set of tasks or a checklist to be accomplished. The perceived
      procedural approach to implementation may be contributing to lower rates of
      breastfeeding continuation.

PMID- 21878130
TI  - Perspective on sequence evolution of microsatellite locus (CCG)n in Rv0050 gene
      from Mycobacterium tuberculosis.
AB  - BACKGROUND: The mycobacterial genome is inclined to polymerase slippage and a
      high mutation rate in microsatellite regions due to high GC content and absence
      of a mismatch repair system. However, the exact molecular mechanisms underlying
      microsatellite variation have not been fully elucidated. Here, we investigated
      mutation events in the hyper-variable trinucleotide microsatellite locus MML0050
      located in the Rv0050 gene of W-Beijing and non-W-Beijing Mycobacterium
      tuberculosis strains in order to gain insight into the genomic structure and
      activity of repeated regions. RESULTS: Size analysis indicated the presence of
      five alleles that differed in length by three base pairs. Moreover, nucleotide
      gains occurred more frequently than loses in this trinucleotide microsatellite.
      Mutation frequency was not completely related with the total length, though the
      relative frequency in the longest allele was remarkably higher than that in the
      shortest. Sequence analysis was able to detect seven alleles and revealed that
      point mutations enhanced the level of locus variation. Introduction of an
      interruptive motif correlated with the total allele length and genetic lineage,
      rather than the length of the longest stretch of perfect repeats. Finally, the
      level of locus variation was drastically different between the two genetic
      lineages. CONCLUSION: The Rv0050 locus encodes the bifunctional penicillin
      binding protein ponA1 and is essential to mycobacterial survival. Our
      investigations of this particularly dynamic genomic region provide insights into
      the overall mode of microsatellite evolution. Specifically, replication slippage
      was implicated in the mutational process of this microsatellite and a sequence
      based genetic analysis was necessary to determine that point mutation events
      acted to maintain microsatellite size integrity while providing genomic
      diversity.

PMID- 21878133
TI  - Self-propagating high-temperature synthesis of nano-TiCx particles with different
      shapes by using carbon nano-tube as C source.
AB  - With using the carbon nano-tube (CNT) of high chemical activity, nano-TiCx
      particles with different growth shapes were synthesized through the self
      propagating high temperature in the 80 wt.% metal (Cu, Al, and Fe)-Ti-CNT
      systems. The growth shapes of the TiCx particles are mainly octahedron in the Cu-
      and Al-Ti-CNT systems, while mainly cube- and sphere-like in the Fe-Ti-CNT
      system.

PMID- 21878132
TI  - Physicians are a key to encouraging cessation of smoking among people living with
      HIV/AIDS: a cross-sectional study in the Kathmandu Valley, Nepal.
AB  - BACKGROUND: HIV care providers may be optimally positioned to promote smoking
      behaviour change in their patients, among whom smoking is both highly prevalent
      and uniquely harmful. Yet research on this front is scant, particularly in the
      developing country context. Hence, this study describes smoking behaviour among
      people living with HIV/AIDS (PLWHA) in the Kathmandu Valley of Nepal, and
      assesses the association between experience of physician-delivered smoking status
      assessment and readiness to quit among HIV-positive smokers. METHODS: We
      conducted a cross-sectional survey of PLWHA residing in the Kathmandu Valley,
      Nepal. Data from 321 adult PLWHA were analyzed using multiple logistic regression
      for correlates of current smoking and, among current smokers, of motivational
      readiness to quit based on the transtheoretical model (TTM) of behaviour change.
      RESULTS: Overall, 47% of participants were current smokers, with significantly
      higher rates among men (72%), ever- injecting drug users (IDUs), recent (30-day)
      alcohol consumers, those without any formal education, and those with higher HIV
      symptom burdens. Of 151 current smokers, 34% were thinking seriously of quitting
      within the next 6 months (contemplation or preparation stage of behaviour
      change). Adjusting for potential confounders, experience of physician-delivered
      smoking status assessment during any visit to a hospital or clinic in the past 12
      months was associated with greater readiness to quit smoking (AOR = 3.34; 95% CI
      = 1.05,10.61). CONCLUSIONS: Roughly one-third of HIV-positive smokers residing in
      the Kathmandu Valley, Nepal, are at the contemplation or preparation stage of
      smoking behaviour change, with rates significantly higher among those whose
      physicians have asked about their smoking status during any clinical interaction
      over the past year. Systematic screening for smoking by physicians during routine
      HIV care may help to reduce the heavy burden of smoking and smoking-related
      morbidity and mortality within HIV-positive populations in Nepal and similar
      settings.

PMID- 21878134
TI  - More than just B-cell inhibition.
AB  - Despite tremendous advances in the therapy of rheumatoid arthritis (RA), there
      remains interest in oral agents that may offer benefits that are similar to, or
      better than, those of biologic therapies. In their paper, Chang and colleagues
      demonstrate the effectiveness of a Bruton tyrosine kinase (Btk) inhibitor in two
      models of RA. Btk inhibition impacts several pathways affecting both B-cell and
      macrophage activation, making it a promising target in RA. However, other kinase
      inhibitors have failed to transition from animal models to human therapy, so it
      remains to be seen whether a Btk inhibitor will have a role in the RA treatment
      armamentarium.

PMID- 21878136
TI  - Worry, beliefs about worry and problem solving in young children.
AB  - BACKGROUND: Childhood worry is common, and yet little is known about why some
      children develop pathological worry and others do not. Two theories of adult
      worry that are particularly relevant to children are Davey's problem-solving
      model in which perseverative worry occurs as a result of thwarted problem-solving
      attempts, and Wells' metacognitive model, in which positive and negative beliefs
      about worry interact to produce pathological worry. AIMS: The present study aimed
      to test hypotheses that levels of worry in young children are associated with
      poor or avoidant solution generation for social problems, and poor problem
      solving confidence. It also aimed to explore beliefs about worry in this age
      group, and to examine their relationships with worry, anxiety and age. METHOD:
      Fifty-seven young children (6-10 years) responded to open ended questions about
      social problem-solving situations and beliefs about worry, and completed measures
      of worry, anxiety and problem-solving confidence. RESULTS: Children with higher
      levels of worry and anxiety reported using more avoidant solutions in social
      problem situations and children's low confidence in problem solving was
      associated with high levels of worry. Children as young as 6 years old reported
      both positive and negative beliefs about worry, but neither were associated with
      age, gender, or level of anxiety or worry. CONCLUSIONS: RESULTS indicate
      similarities between adults and children in the relationships between problem
      solving variables and worry, but not in relationships between beliefs about worry
      and worry. This may be due to developmental factors, or may be the result of
      measurement issues.

PMID- 21878137
TI  - Imagery and pain: the prevalence, characteristics, and potency of imagery
      associated with pain.
AB  - BACKGROUND: There is a dearth of information about imagery in pain sufferers.
      AIM: The aim of this study was to collect data on the characteristics,
      prevalence, and potency of imagery associated with pain. METHOD: The images of 59
      pain sufferers were assessed by means of a semi-structured interview. The
      emotional, cognitive, behavioural, and pain-inducing properties (potency) of
      their index images were assessed by an image induction procedure and self-report
      scales of anxiety, depression and trauma symptoms. RESULTS: The results showed a
      remarkably high incidence of images in pain sufferers, with 78% of participants
      reporting one or more repetitive images when in pain. Exposure to their most
      powerful/distressing image (Index image) resulted in significant increases in
      negative emotions, negative cognitive appraisals, and in pain levels. In a sub
      group of sufferers with significant levels of trauma symptoms, the index images
      elicited significantly higher levels of emotion and pain increment than did those
      respondents in a low/no trauma group. CONCLUSION: It was concluded that imagery
      is a prevalent, often "unobserved" but potent cognition in pain sufferers. The
      implications for CBT approaches to chronic pain, including image rescripting, are
      considered.

PMID- 21878135
TI  - Heart failure.
AB  - INTRODUCTION: Heart failure occurs in 3% to 4% of adults aged over 65 years,
      usually as a consequence of coronary artery disease or hypertension, and causes
      breathlessness, effort intolerance, fluid retention, and increased mortality. The
      5-year mortality in people with systolic heart failure ranges from 25% to 75%,
      often owing to sudden death following ventricular arrhythmia. Risks of
      cardiovascular events are increased in people with left ventricular systolic
      dysfunction (LVSD) or heart failure. METHODS AND OUTCOMES: We conducted a
      systematic review and aimed to answer the following clinical questions: What are
      the effects of multidisciplinary interventions for heart failure? What are the
      effects of exercise in people with heart failure? What are the effects of drug
      treatments for heart failure? What are the effects of devices for treatment of
      heart failure? What are the effects of coronary revascularisation for treatment
      of heart failure? What are the effects of drug treatments in people at high risk
      of heart failure? What are the effects of treatments for diastolic heart failure?
      We searched: Medline, Embase, The Cochrane Library, and other important databases
      up to August 2010 (Clinical Evidence reviews are updated periodically; please
      check our website for the most up-to-date version of this review). We included
      harms alerts from relevant organisations such as the US Food and Drug
      Administration (FDA) and the UK Medicines and Healthcare products Regulatory
      Agency (MHRA). RESULTS: We found 80 systematic reviews, RCTs, or observational
      studies that met our inclusion criteria. We performed a GRADE evaluation of the
      quality of evidence for interventions. CONCLUSIONS: In this systematic review we
      present information relating to the effectiveness and safety of the following
      interventions: aldosterone receptor antagonists, amiodarone, angiotensin
      converting enzyme inhibitors, angiotensin II receptor blockers, anticoagulation,
      antiplatelet agents, beta-blockers, calcium channel blockers, cardiac
      resynchronisation therapy, coronary revascularisation, digoxin (in people already
      receiving diuretics and angiotensin-converting enzyme inhibitors), exercise,
      hydralazine plus isosorbide dinitrate, implantable cardiac defibrillators,
      multidisciplinary interventions, non-amiodarone antiarrhythmic drugs, and
      positive inotropes (other than digoxin).

PMID- 21878138
TI  - Body-related behaviours and cognitions: relationship to eating psychopathology in
      non-clinical women and men.
AB  - BACKGROUND: Eating disturbances and poor body image are maintained by body
      related safety behaviours and their associated cognitions. These include body
      checking, avoidance, comparison and display, which can be seen as safety
      behaviours, maintaining eating pathology and poor body image. It is not clear
      from the existing literature whether these behavioural and cognitive patterns are
      independently related to eating psychopathology. METHOD: This study of a non
      clinical group of women and men (N = 250) explored the association of eating
      attitudes and behaviours with these four elements of body-related behaviours and
      cognitions. RESULTS: It was found that each of the four elements had independent
      associations with eating attitudes and behaviours. Those associations were not
      explained by anxiety or depression levels. DISCUSSION: Whilst these findings
      require study within a clinical group, they suggest that all four elements of
      body-related behaviours and cognitions need to be considered as potential
      maintaining factors when formulating eating psychopathology and body image
      disturbance.

PMID- 21878140
TI  - Offspring production and self-superparasitism in the solitary ectoparasitoid
      Spalangia cameroni (Hymenoptera: Pteromalidae) in relation to host abundance.
AB  - Parasitoid fitness strongly depends on the availability and quality of hosts,
      which provide all resources required for larval development. Several factors,
      such as host size and previous parasitation, may affect host quality. Because
      self-superparasitism induces competition among a female's offspring, it should
      only occur if there is an imperfect recognition of self-parasitized hosts or if
      there is a fitness advantage to self-superparasitism. Against this background, we
      investigated self-superparasitism and offspring production in Spalangia cameroni
      (Hymenoptera: Pteromalidae) in relation to the abundance of a novel host,
      Ceratitis capitata (Diptera: Tephritidae). Individual pairs of parasitoids were
      provided with either two (low host abundance) or ten (high host abundance) pupae
      per day. Under high host abundance, lifetime fecundity (number of eggs laid),
      offspring number, number of pupae parasitized and hosts killed were greater than
      under low host abundance, whereas the number of eggs per host was lower; and the
      proportion of hosts that did not produce offspring tended to be lower. The latter
      suggests the occurrence of ovicide, when hosts are scarce due to an at least
      imperfect recognition of previously self-parasitized hosts. Offspring production
      per parasitized pupa was higher when hosts were scarce and levels of self
      superparasitism high, suggesting the existence of beneficial effects of self
      superparasitism.

PMID- 21878141
TI  - Body fat and fat-free mass measured by bioelectric impedance spectroscopy and
      dual-energy X-ray absorptiometry in obese and non-obese adults.
AB  - The aim of the present study was to compare body fat mass (FM) and fat-free mass
      (FFM) estimates by bioelectric impedance spectroscopy (BIS), with respective
      estimates by dual-energy X-ray absorptiometry (DXA), in obese and non-obese
      subjects. Body composition was measured in ninety-three obese and non-obese men
      and women by BIS device, BodyScout (Fresenius Kabi, Bad Homburg, Germany) and DXA
      device, Lunar iDXA (GE Healthcare, Madison, WI, USA). Mean difference between the
      methods was analysed by t tests, and Bland-Altman plots were generated to further
      examine the differences between the methods. Mean difference between the
      estimates by DXA and BIS (DeltaDXA - BIS and Bland-Altman 95 % limits of
      agreement) were as follows: FM 4.1 ( - 2.9, 11.2) kg and 4.5 ( - 2.9, 11.8) %,
      FFM - 4.1 ( - 11.2, 2.9) kg and - 4.5 ( - 11.9, 2.9) %, indicating large inter
      individual variation and statistically significant underestimation of FM and
      overestimation of FFM by BIS, as compared to DXA. The underestimation of FMkg (FM
      measured in kg) and overestimation of FFMkg (FFM measured in kg) were more
      pronounced in men than in women, and the underestimation of FM% (FM measured in
      percent) and overestimation of FFM% (FFM measured in percent) were more
      pronounced in normal weight (BMI = 20.0-24.9 kg/m2) than in overweight and obese
      (BMI >= 25.0 kg/m2) subjects. BIS may be suitable for classification of a
      population into groups according to FM and FFM. However, the large inter
      individual variation suggests that this BIS device with the proprietary software
      is insufficient for estimation of single individual body FM and FFM.

PMID- 21878142
TI  - Single coronary artery-right ventricular fistula.
AB  - We report a rare case of a male child aged 4 years and 5 months who was diagnosed
      with a coronary artery fistula and left single coronary artery. Pre-operative
      evaluation with echocardiography and selective angiography showed a dilated and
      tortuous single coronary artery draining into the right ventricular outflow
      tract. The coronary fistula was ligated. The post-operative and clinical courses
      were uneventful.

PMID- 21878143
TI  - Precocious virulent coronary atherosclerosis in the very young.
AB  - BACKGROUND: The incidence of Myocardial Infarction (MI) in patients under the age
      of 30 has been rarely addressed. Moreover, it is not understood why these
      patients develop symptomatic Coronary Artery Disease (CAD) at such an early age.
      Traditional risk factor assessment has not been successful in identifying these
      patients before they present with MI. METHODS: Retrospective, single cohort,
      observational study of 14,704 cardiac catheterizations performed in a community
      hospital between January 2006-January 2010 identified 12 cases age <30 with MI
      secondary to a fixed atherosclerotic lesion requiring angioplasty and stenting.
      The angiograms and charts were reviewed to assess the incidence and frequency of
      traditional risk factors such as smoking, dyslipidemia and diabetes and family
      history. RESULTS: All the patients had single vessel disease. Many of the
      patients were noted to have traditional CAD risk factors. 2 patients had an
      intervention and then months later sustained another acute MI secondary to a new
      culprit lesion despite aggressive risk factor modification. CONCLUSION:
      Evaluating patients for premature CAD by screening for traditional risk factors
      has not effectively identified at risk patients prior to presentation with MI.
      There is a role for studies evaluating new and novel risk factors and imaging
      modalities so that these patients can be identified prior to experiencing MI.

PMID- 21878144
TI  - Multipoint maximum likelihood mapping in a full-sib family of an outbreeding
      species.
AB  - The fast multipoint maximum likelihood mapping algorithm for crosses between
      inbred lines, introduced by Jansen et al. (2001), is extended for mapping in a
      full-sib family of an outbreeding species. The method accommodates different
      segregation types of markers and differences in recombination between parents.
      The two separate parental multipoint maximum likelihood maps are joined into an
      integrated map by averaging lengths over anchored segments and by interpolating
      or extrapolating for markers segregating in one parent only. The method is
      illustrated with simulated data. The method will enable a more accurate
      estimation of maps in outbreeding species than current methods.

PMID- 21878145
TI  - Epidemiology of hand, foot, and mouth disease in children in Shanghai 2007-2010.
AB  - We retrospectively analysed the epidemiological data of all hand, foot, and mouth
      disease (HFMD) cases from the largest paediatric infectious diseases centre in
      Shanghai between 2007 and 2010. A total of 28 058 outpatients were diagnosed with
      HFMD, of which 3948 (14.07%) were hospitalized, 730 (2.60%) had complications
      with neurological disorders and pulmonary oedema/haemorrhage, and 11 (0.04%)
      died. The peak season was the summer months. Boys were more affected than girls.
      Since 2008, the major population group affected has shifted from native
      Shanghainese children attending preschool to migrant children and younger
      children cared for at home. Children aged 1-4 years constituted 82.27% of cases.
      EV-A71 was tested in clinical samples taken from severe cases in 2009 and 2010,
      and from most inpatients in 2010. EV-A71 was positive in 99.17% and 86.31% of
      severe cases, respectively in 2009 and 2010. All 12 cases with pulmonary oedema
      or haemorrhage were infected with EV-A71. Ten (90.90%) of 11 fatal cases were
      attributable to EV-A71 infection. In 2010, EV-A71-positive cases accounted for
      54.12% of inpatients. The dominant circulation of EV-A71 led to the outbreak of
      HFMD and occurrence of severe and fatal cases.

PMID- 21878146
TI  - Time-series model to predict impact of H1N1 influenza on a children's hospital.
AB  - The spring of 2009 witnessed the emergence of a novel influenza A(H1N1) virus
      resulting in the first influenza pandemic since 1968. In autumn of 2010, the 2009
      novel H1N1 influenza strain re-emerged. We performed a retrospective time-series
      analysis of all patients with laboratory-confirmed H1N1 influenza who presented
      to our institution during 2009. Cases of influenza were assembled into 3-day
      aggregates and forecasting models of H1N1 influenza incidence were created.
      Forecasting estimates of H1N1 incidence for the 2010-2011 season were compared to
      actual values for our institution to assess model performance. Ninety-five
      percent confidence intervals calculated around our model's forecasts were
      accurate to +/-3.6 cases per 3-day period for our institution. Our results
      suggest that time-series models may be useful tools in forecasting the incidence
      of H1N1 influenza, helping institutions to optimize distribution of resources
      based on the changing burden of illness.

PMID- 21878147
TI  - Seroepidemiology of Toxoplasma gondii infection in women from the North of
      Portugal in their childbearing years.
AB  - Seroprevalence of Toxoplasma gondii infection and associated risk factors were
      investigated in 401 women of childbearing age from the North of Portugal. Of the
      98 (24.4%) seropositive women, 92 (93.9%) only had immunoglobulin (Ig)G, two
      (2.0%) only had IgM, and four (4.1%) others had both IgG and IgM. Risk factors
      for T. gondii infection in women were: engaging in soil-related activities
      without gloves [odds ratio (OR) 8.4], consumption of unwashed raw vegetables or
      fruit (OR 7.6), and consumption of smoked or cured (non-cooked) processed pork
      products (OR 2.5). Most women of childbearing age from the North Portugal are
      susceptible to primary infection with T. gondii and, therefore, the risk of
      congenital toxoplasmosis remains high.

PMID- 21878148
TI  - Early vocabulary and gestures in Estonian children.
AB  - Parents of 592 children between the age of 0 ; 8 and 1 ; 4 completed the Estonian
      adaptation of the MacArthur-Bates Communicative Development Inventory (ECDI
      Infant Form). The relationships between comprehension and production of different
      categories of words and gestures were examined. According to the results of
      regression modelling the production of object gestures and gestural routines was
      positively correlated with the use of all the word categories. Comprehension of
      common nouns was positively correlated to the production of common nouns and
      predicates, whereas the comprehension of predicates was negatively correlated to
      the production of common nouns and social terms. The older the children were the
      more they produced words from each category. Girls were reported to produce more
      social terms. First-born children had an advantage over later-born children in
      the production of common nouns. Maternal educational level was associated with
      the production of common nouns and predicates.

PMID- 21878149
TI  - The three-dimensional point spread function of aberration-corrected scanning
      transmission electron microscopy.
AB  - Aberration correction reduces the depth of field in scanning transmission
      electron microscopy (STEM) and thus allows three-dimensional (3D) imaging by
      depth sectioning. This imaging mode offers the potential for sub-Angstrom lateral
      resolution and nanometer-scale depth sensitivity. For biological samples, which
      may be many microns across and where high lateral resolution may not always be
      needed, optimizing the depth resolution even at the expense of lateral resolution
      may be desired, aiming to image through thick specimens. Although there has been
      extensive work examining and optimizing the probe formation in two dimensions,
      there is less known about the probe shape along the optical axis. Here the probe
      shape is examined in three dimensions in an attempt to better understand the
      depth resolution in this mode. Examples are presented of how aberrations change
      the probe shape in three dimensions, and it is found that off-axial aberrations
      may need to be considered for focal series of large areas. It is shown that
      oversized or annular apertures theoretically improve the vertical resolution for
      3D imaging of nanoparticles. When imaging nanoparticles of several nanometer
      size, regular STEM can thereby be optimized such that the vertical full-width at
      half-maximum approaches that of the aberration-corrected STEM with a standard
      aperture.

PMID- 21878151
TI  - The use of seclusion and restraint in psychiatry.

PMID- 21878152
TI  - Psychotherapy training of psychiatrists.

PMID- 21878154
TI  - Early life and the development of resilience.

PMID- 21878155
TI  - Parenting behaviours associated with the development of adaptive and maladaptive
      offspring personality traits.
AB  - OBJECTIVES: To investigate the associations of beneficial parenting behaviours
      with adaptive and maladaptive offspring personality traits that persist into
      adulthood among individuals in the community. METHODS: Families (n = 669)
      participating in the Children in the Community Study were interviewed during the
      childhood, adolescence, emerging adulthood, and adulthood of the offspring at the
      mean ages of 6, 14, 16, 22, and 33 years. RESULTS: Twelve types of beneficial
      maternal and paternal child-rearing behaviour, reported by offspring at the mean
      age of 16 years, were associated with elevated offspring personality resiliency,
      at the mean ages of 22 and 33 years, and with low offspring personality disorder
      trait levels. These longitudinal associations remained significant when histories
      of childhood behaviour problems and parental psychiatric disorder were controlled
      statistically. Similar linear (that is, dose-dependent) associations were
      observed between the number of beneficial parenting behaviours during childhood
      and adaptive and maladaptive offspring traits at the mean ages of 22 and 33
      years. Maternal and paternal behaviours were independently associated with both
      adaptive and maladaptive offspring traits. CONCLUSIONS: Beneficial maternal and
      paternal child-rearing behaviours may promote the development of adaptive
      offspring personality traits that endure into adulthood, and they may be
      prospectively associated with reduced levels of maladaptive offspring traits.
      These associations may not be attributable to childhood behaviour problems or
      parental psychiatric disorders, and they may be equally evident during early and
      middle adulthood.

PMID- 21878156
TI  - The relation between adolescent social competence and young adult delinquency and
      educational attainment among at-risk youth: the mediating role of peer
      delinquency.
AB  - OBJECTIVE: We examined trajectories of adolescent social competence as a
      resilience factor among at-risk youth. To examine potential mechanisms of this
      resilience process, we investigated the putative mediating effect of peer
      delinquency on the relation between adolescent social competence and young adult
      delinquency seriousness and educational attainment. METHOD: Participants (n =
      257) were screened to be at risk for antisocial behaviour at age 13 years. Data
      were derived from an ongoing longitudinal study of the development of antisocial
      and delinquent behaviour among inner-city boys, the Pittsburgh Youth Study. We
      used data collected from participants when aged 13 years until they were aged
      25.5 years for our study. RESULTS: Results indicated that boys with high levels
      of social competence decreased their involvement with deviant peers throughout
      adolescence, which, in turn, predicted less serious forms of delinquency in early
      adulthood. Social competence had a direct effect on educational attainment in
      early adulthood, as boys who developed social competencies in adolescence went
      further in school irrespective of their involvement with delinquent peers.
      CONCLUSIONS: Results suggest that promoting the development of social
      competencies and reducing involvement with delinquent peers will protect at-risk
      youth from engaging in serious delinquency in early adulthood while increasing
      their educational success.

PMID- 21878157
TI  - Risk factors for depression in older adults in Beijing.
AB  - OBJECTIVE: Depression is a common mental disorder in older adults. We examined
      the prevalence and risk factors for depression in older adults in the Beijing
      area. METHOD: We used data from a cross-sectional survey conducted in July 2006
      in Beijing. As part of the national survey for older Chinese adults, 2002 older
      adults were interviewed. The 15-item Geriatric Depression Scale was used to
      assess depression. Demographics as well as other personal information were also
      collected. RESULTS: Among Beijing older adults, 13.01% were categorized as
      depressed. Prevalence rates of depression in rural and urban older adults were
      26.63% and 10.79%, respectively. Poor economic status, high activities of daily
      living (ADL) score, poor physical health, impious offspring, and feeling old were
      important predictors of depression in older adults in Beijing. For the urban
      sample, poor economic status, poor physical health, high ADL score, and impious
      offspring were risk factors for depression. For the rural sample, depression was
      significantly associated with poor economic status and poor physical health.
      CONCLUSIONS: Depression is a common mood disorder among older adults in the
      Beijing area. Filial piety is a unique predictor for depression in older Chinese
      adults, compared with findings in Western cultures.

PMID- 21878158
TI  - Access to and waiting time for psychiatrist services in a Canadian urban area: a
      study in real time.
AB  - OBJECTIVE: To obtain improved quality information regarding psychiatrist waiting
      times by use of a novel methodological approach in which accessibility and wait
      times are determined by a real-time patient referral procedure. METHOD: An adult
      male patient with depression was referred for psychiatric assessment by a family
      physician. Consecutive calls were made to all registered psychiatrists (n = 297)
      in Vancouver. A semistructured call procedure was used to collect information
      about the psychiatrists' availability for receipt of this and similar referrals,
      identify factors that affect psychiatrist accessibility, and determine the
      availability of cognitive-behavioural therapy (CBT). RESULTS: Efforts were made
      to contact 297 psychiatrists and 230 (77%) were reached successfully. Among the
      230 psychiatrists contacted, 160 (70%) indicated that they were unable to accept
      the referral. Although 70 (30%) indicated that they might be able to consider
      accepting a referral, 64 (91% of those who would consider accepting the referral)
      indicated that they would need to review detailed, written referral information
      and could not provide estimates of the length of wait times if the patient was to
      be accepted. Only 6 (3% of the 230 psychiatrists contacted) offered immediate
      appointment times and their wait times ranged from 4 to 55 days. When asked
      whether they could provide CBT, most (56%) psychiatrists in clinical practice
      answered maybe. CONCLUSIONS: Substantial barriers exist for family physicians
      attempting to refer patients for psychiatric referral. Consolidated efforts to
      improve access to psychiatric assessment are needed.

PMID- 21878159
TI  - Postdischarge care for depression in Ontario.
AB  - OBJECTIVE: People hospitalized for depression are often discharged before the
      acute phase of their illness has resolved and need timely care transitions to
      prevent relapse. We examined 30-day postdischarge service use for Ontarians, aged
      15 years or older, who were hospitalized for depression. We focused on a pattern
      consistent with guideline and policy directions: higher rates of physician
      visits, postdischarge, combined with lower rates of emergency department (ED)
      admissions or rehospitalization. METHODS: Administrative data for the fiscal year
      of 2005 were used to identify hospitalizations for depression and subsequent
      physician visits, ED admissions, or readmissions for depression within 30 days,
      postdischarge. Sex, age, income, and geographic location were examined along with
      the relation between health care resources (beds, EDs, and physicians) and
      postdischarge service use. RESULTS: Sixty-three percent of patients discharged
      for depression were followed, within 30 days, by a physician visit for
      depression. Twenty-five percent were either rehospitalized or visited an ED.
      Women and people from urban or high income areas were more likely to have
      postdischarge physician visits. Readmissions and ED visits were correlated with
      number of EDs, but postdischarge physician visits were not related to the number
      of general practitioners, family physicians, and psychiatrists in the local area.
      CONCLUSION: One-third of Ontarians hospitalized for depression did not receive
      recommended follow-up outpatient care within 30 days of discharge and one-quarter
      received follow-up through ED visits or readmissions, highlighting the need to
      improve coordination and integration across care settings for these patients.
      There are tested transitional and outpatient models that improve quality and
      outcomes of depression care that merit serious consideration.

PMID- 21878160
TI  - Association of mental health with health care use and cost: a population study.
AB  - OBJECTIVE: To compare the health costs of groups with and without psychiatric
      diagnoses (PDs) using 9 years of physician billing data. METHODS: A dataset
      containing registration data for all patients receiving public mental health
      service was constructed and subsequently matched, on age and sex, in a final
      patient to comparison patient ratio of 1:8, with health care users who did not
      receive treatment in the mental health system. Three groups emerged: a patient PD
      group-patients with psychiatric disorders treated in public mental health care (n
      = 76 677); a comparison patient PD group-comparison patients with PDs treated in
      physicians only (n = 277 627); and a patient- comparison patient non-PD group
      patients (treated in specialized publicly funded care or by their physician)
      without PDs (n = 329 177). Examining over 42 million billing records for all of
      these patients, we compared the average number of visits and the average health
      only (nonpsychiatric) billing cost per each patient during the 9-year study
      period across the groups. RESULTS: Among all health care users in the data, the
      health costs (Total Costs - Mental Health Costs) were greater on average for the
      patients with PD group ($3437) and the comparison patient PD group ($3265),
      compared with patient-comparison patient non-PD group ($1345). Forty-six percent
      of the comparison sample had a PD. CONCLUSIONS: Having a mental health problem is
      related to greater health-related expenditures. This has important policy
      implications on how mental health resources are constructed and rationed within
      the health care system.

PMID- 21878161
TI  - Nonmedical prescription opioid use and mental health and pain comorbidities: a
      narrative review.
AB  - OBJECTIVE: In North America, the prevalence of nonmedical prescription opioid use
      (NMPOU), and morbidity and mortality related to prescription opioid analgesics
      (POAs) has risen sharply. Epidemiologic studies have suggested a high prevalence
      of mental health and pain comorbidities in NMPOU samples. Given the potential
      importance for interventions, a narrative review was conducted on studies
      reporting data on the co-occurrence of NMPOU with mental health problems and pain
      symptoms in general, treatment, or special populations. METHOD: A search of
      MEDLINE, PubMed, PsycINFO, and Web of Science using defined search terms yielded
      74 studies on NMPOU and mental health and (or) pain. Thirty-nine studies
      published between 1997 and 2009 were included in the review-based on the data
      they provided on NMPOU and mental health and pain comorbidities. RESULTS: Our
      review found strong associations between NMPOU and the comorbidities of interest.
      Associations between NMPOU and mental health were strongest for depression (OR
      range 1.2 to 4.3) followed by anxiety disorders (OR range 1.2 to 3.0) in general
      and treatment populations. The prevalence of pain ranged from 14.5% to 61.5% in
      general, treatment, and street drug user samples reporting NMPOU. CONCLUSIONS:
      The extensive associations observed between NMPOU and mental health and pain
      comorbidities suggest that effective preventive or treatment interventions for
      NMPOU must consider and attend to these comorbidities. As POAs are widely
      available and used in North America, POAs may increasingly be used in nonmedical
      ways for pain or mental health problems not effectively diagnosed or treated.

PMID- 21878162
TI  - Long-term effects of short-term psychodynamic psychotherapy and cognitive
      behavioural therapy in generalized anxiety disorder: 12-month follow-up.
AB  - OBJECTIVE: In a previous randomized controlled trial (RCT), short-term efficacy
      of cognitive-behavioural therapy (CBT) and short-term psychodynamic psychotherapy
      (STPP) in generalized anxiety disorder (GAD) was demonstrated. In this article,
      long-term stability of these effects will be examined. Effects of CBT and STPP
      will be compared. METHOD: In the original RCT, patients with GAD were treated
      with either CBT (n = 29) or STPP (n = 28). Treatments were carried out according
      to manuals and included up to 30 sessions. As the primary outcome measure the
      Hamilton Anxiety Rating Scale was used. In addition to short-term outcome
      previously reported, treatment effects were assessed 12 months after termination
      of treatment. RESULTS: Both CBT and STPP yielded large improvements at 12-month
      follow-up. No significant differences were found between treatments concerning
      the primary outcome measure. This result was corroborated by 3 self-report
      measures of anxiety. However, in measures of trait anxiety and worry, CBT was
      superior. Concerning depression, differences reported at posttreatment were no
      longer significant at 12-month follow-up. CONCLUSIONS: In GAD, both CBT and STPP
      yield large and stable effects 12 months after treatment. Concerning trait
      anxiety and worry, CBT seems to be superior. For STPP, further studies should be
      carried out to confirm the results.

PMID- 21878163
TI  - Association between antidepressant use during pregnancy and infants born small
      for gestational age.

PMID- 21878164
TI  - Electroconvulsive therapy: the name resurrected.

PMID- 21878165
TI  - [Analysis of risk factors of prolonged intensive care unit stay of critically ill
      obstetric patients: a 5-year retrospective review in 3 hospitals in Beijing].
AB  - OBJECTIVE: To identify the risk factors of prolonged intensive care unit (ICU)
      stay of critically ill obstetric patients. METHODS: A retrospective analysis of
      cases of critically ill obstetric patients admitted to the ICUs of Peking
      University Third Hospital, Capital Medical University Affiliated Beijing Chaoyang
      Hospital, and PLA 306 Hospital from January 1st 2006 to December 31st 2010 was
      made. Data included demographics, causes of critical illness or complications
      that prompted ICU admission, the acute physiology and chronic health evaluation
      II (APACHEII) scores, the time intervals between onset of acute symptoms and ICU
      admission, laboratory test results, treatment measures, length of ICU stay and
      the final maternal mortality. Data were used to identify univariate and
      multivariate predictors for prolonged ICU stay. RESULTS: During the 5-year period
      there were 207 obstetric patients [mean age (31.74+/-2.32) years old, mean
      gestational age (34.86+/-4.72) weeks] were transferred to the ICU for critical
      care (42 ICU admissions per 10 000 deliveries), and among them 4 women died
      (mortality rate 1.93%). The pathogenesis of the cases could be divided into
      direct obstetric pathologies (n=138) and indirect or coincidental pathologies
      (n=69). The most common obstetric causes of admission were massive postpartum
      haemorrhage (n=42, 20.29%) and pregnancy associated hypertension (n=36, 17.39%),
      followed by acute fatty liver of pregnancy (AFLP, n=27, 13.04%), obstetric
      disseminated intravascular coagulation (DIC, n=23, 11.11%). The most common non
      obstetric causes of admission were acute heart failure (n=26, 12.56%) and acute
      respiratory failure (n=22, 10.63%), followed by severe acute pancreatitis (SAP,
      n=11, 5.31%). The incidence of prolonged ICU stay (ICU stay >3 days) was 52.66%
      (n=109). Univariate predictors of prolonged ICU stay included inadvertent
      antenatal care, high serum creatinine, abnormal international normalized ratio of
      prothrombin time (INR), abnormal oxygenation index (PaO(2)/FiO(2)), AFLP,
      obstetric DIC, SAP, use of mechanical ventilation, indications for inotropic
      support, and blood purification, and >24 hour interval between onset of acute
      symptoms and ICU admission. Multivariate modeling identified that inadvertent and
      irregular antenatal care [odds ratio (OR) 1.68, 95% confidence interval (95%CI)
      1.14-2.69, P=0.011], PaO(2)/FiO(2) (OR 4.73, 95%CI 1.46-11.37, P=0.013), AFLP
      (OR3.21, 95%CI 1.13-4.76, P=0.026), DIC (OR 2.73, 95%CI 1.28-4.02, P=0.018), SAP
      (OR 4.78, 95%CI 1.83-7.42, P=0.021 ), indications for inotropic support (OR 1.96,
      95%CI 1.24-3.15, P=0.001), blood purification (OR 11.02, 95%CI 3.04-58.02,
      P=0.015) and >24 hour interval between onset of acute symptoms and ICU admission
      (OR 2.04, 95%CI 1.21-4.25, P<0.001) were the independent predictors for prolonged
      ICU stay. CONCLUSION: The incidence of prolonged ICU stay is high for critically
      ill obstetric patients. Patients with identified multivariate predictors carry a
      high risk of prolonged ICU stay, they may benefit from enhanced regular antenatal
      care, prevention of critical obstetric and medical complications, shortening the
      interval between onset of acute symptoms and ICU admission and strengthening the
      support of organ function.

PMID- 21878166
TI  - [Effect of mesenteric lymph obtained during shock on pump activity and oxygen
      free radical on erythrocyte membrane of rat].
AB  - OBJECTIVE: To observe the effects of mesenteric lymph drainage and transfusion on
      pump activity and oxygen free radical of erythrocyte membrane of rats following
      hemorrhagic shock or normal, respectively. METHODS: Twenty-four male Wistar rats
      were randomly divided into sham-shock group, shock group, shock mesenteric lymph
      drainage group (drainage group) and shock mesenteric lymph transfusion group
      (transfusion group) by randomization, with 6 rats in each group. Model of
      hemorrhagic shock was reproduced both in shock group and drainage group after
      anesthesia and operation, mesenteric lymph was drained 1 hour after shock in
      drainage group. Sham-shock group only received anesthesia and laparotomy, and the
      obtained mesenteric lymph was transfused in transfusion group. Blood was obtained
      from abdominal aorta, and red cell membrane suspension was prepared after 3 hours
      of shock or corresponding time, then the indices of erythrocyte membrane pump
      activity and oxygen free radical were determined. RESULTS: Compared with sham
      shock group, the activity of Na(+)-K(+)-ATPase (MUmol*mg(-1)*h(-1)), Ca(2+)
      ATPase (MUmol*mg(-1) *h(-1) ) and superoxide dismutase (SOD) (NU/mg)of red cell
      membrane were decreased markedly (Na(+)-K(+)-ATPase: 0.039+/-0.011 vs. 0.068+/
      0.010; Ca(2+)-ATPase: 0.035+/-0.016 vs. 0.087+/-0.015; SOD: 0.785+/-0.289 vs.
      1.202+/-0.328, P<0.05 or P<0.01), and the content of malondialdehyde (MDA,
      nmol/mg) was increased markedly in shock group (1.914+/-0.225 vs. 0.913+/-0.138,
      P<0.01). Compared with shock group, the activity of Na(+)-K(+)-ATPase (0.056+/
      0.009), Ca(2+)-ATPase (0.079+/-0.025) and SOD (1.220+/-0.380) of red cell
      membrane were increased in drainage group, and the level of MDA (1.214+/-0.127)
      was decreased markedly (P<0.05 or P<0.01). Compared with sham-shock group, the
      activity of Na(+)-K(+)-ATPase (0.050+/-0.013), Ca(2+)-ATPase (0.056+/-0.023) of
      red cell membrane in transfusion group were significantly lower (both P<0.05),
      the content of MDA (1.456+/-0.270) was significantly higher (P<0.01),
      respectively, the activity of SOD (0.862+/-0.288) showed a lowering trend, but
      there was no statistical significance (P>0.05). CONCLUSION: Mesenteric lymph
      return is a key factor in decreasing pump activity while aggravating free radical
      damage injury of erythrocyte membrane.

PMID- 21878167
TI  - [The effects of fluid resuscitation with different crystalloid-colloid ratio on
      extravascular lung water index in severe acute pancreatitis].
AB  - OBJECTIVE: To investigate the effects of fluid resuscitation with different
      crystalloid-colloid ratio on extravascular lung water (EVLW) in patients with
      severe acute pancreatitis (SAP). METHODS: Clinical data of 24 SAP patients,who
      had undergone intrathoracic blood volume index (ITBVI <750 ml/m(2)),were analyzed
      retrospectively, in Department of Critical Care Medicine in the First Affiliated
      Hospital of Shenzhen University, during January of 2009 to December of 2010.
      ITBVI 850-1 000 ml/m(2) was confirmed the end criterion of the end point of
      resuscitation. Low crystalloid-colloid ratio group (n=13) and high crystalloid
      colloid ratio group (n=11) were divided according to crystalloid-colloid ratio
      (3:1) as the borderline . Hemodynamic parameters, extravascular lung water index
      (EVLWI), oxygenation index (PaO(2)/FiO(2)), bladder pressure (ICP) and B type
      natriuretic peptide (BNP) were observed at the time point of before fluid
      resuscitation, and 0, 24,48, 72 hours after resuscitation, EVLWI was measured
      with thermal dilution pulse index continuous cardiac output (PiCCO), and BNP with
      radioimmunoassay. RESULTS: (1)Hemodynamic parameters can be improved at early
      fluid resuscitation stage in both groups.(2) The total amount of fluid [(16 438+/
      1 758) ml], amount of crystalloid fluid [(13 459+/-425) ml] and crystalloid
      colloid ratio (4.50+/-0.23) of the high crystalloid-colloid ratio group was
      significantly higher than that of the low crystalloid-colloid ratio group [(13
      895+/-1 783) ml, (6 945+/- 454) ml, 2.32+/-0.18, respectively, P<0.05 or P<0.01]
      at the time point of 72 hours after resuscitation. (3) Compared with low
      crystalloid-colloid ratio group, PaO(2)/FiO(2)(mm Hg, 1 mm Hg=0.133 kPa) in high
      crystalloid-colloid ratio group was lowered significantly at 48 hours and 72
      hours after resuscitation (48 hours: 186.51+/-42.26 vs. 268.35+/-34.18, 72 hours
      : 172.85+/-21.50 vs. 263.95+/-24.20); but EVLWI, ICP and BNP were increased
      significantly [EVLWI (ml/kg) 48 hours: 14.52+/-1.08 vs. 10.40+/-1.16, 72 hours:
      14.92+/-0.86 vs. 10.52+/-1.02; ICP (cm H(2)O, 1 cm H(2)O=0.098 kPa) 48 hours:
      16.23+/-1.32 vs. 13.05+/-1.70, 72 hours: 17.39+/-1.56 vs. 13.42+/-1.65; BNP
      (ng/L) 48 hours: 424.29+/-74.25 vs. 225.32+/-53.58, 72 hours: 620.49+/-79.53 vs.
      288.28+/-68.78, P<0.05 or P<0.01]. (4) The Pearson correlation analysis showed
      that: EVLWI with PO(2)/FiO(2) was correlated negatively (r=-0.71, P<0.01), but
      with the BNP, ICP showed positive correlation (r(1)=0.63, r(2)=0.56, both
      P<0.01). CONCLUSION: In order to guide early fluid resuscitation,EVLW, ICP and
      BNP should be monitored and limited fluid resuscitation strategy with an
      increasing colloid ratio should be adopted for SAP patients.

PMID- 21878168
TI  - [Intrathoracic blood volume index as an indicator of fluid management in septic
      shock].
AB  - OBJECTIVE: To investigate the value of intrathoracic blood volume index (ITBVI)
      monitoring in fluid management strategy in septic shock patients. METHODS: In a
      prospective study, 33 patients who were diagnosed to be suffering from septic
      shock in the intensive care unit (ICU) were enrolled . Seventeen patients who
      received pulse indicator continuous cardiac output (PiCCO) monitoring, and ITBVI
      was used as indicator of fluid management, were enrolled into ITBVI group; 16
      patients who received traditional fluid management strategy [directed by central
      venous pressure (CVP)] were enrolled into control group. Acute physiology and
      chronic health evaluation II (APACHEII) score, sepsis related organ failure
      assessment (SOFA) score and vasopressor score were compared between 1 day and 3
      days of treatment. The characteristics of fluid management were recorded and
      compared within 72 hours. RESULTS: (1)In 3 days of treatment, APACHEII, SOFA and
      vasopressor score were significantly lower in ITBVI group compared with that of
      in 1 day of treatment[21.3+/-6.2 vs. 25.4+/-7.2, 6.1+/-3.4 vs. 9.0+/-3.5, 5 (0,
      8.0) vs. 20.0 (8.0, 35.0), respectively, all P<0.01], whereas there were no
      changes in control group. (2)Although fluid output (ml) was higher in ITBVI group
      during 48-72 hours period (2 421+/- 868 vs. 1 721+/-934, P=0.039), there was no
      difference in fluid intake, fluid output or fluid balance (ml) within 0-72 hours
      between two groups (fluid intake: 9 918+/-137 vs. 10 529+/-1 331, fluid output :
      6 035+/-1 739 vs. 5 827+/-2 897, fluid balance: 3 882+/-1 889 vs. 4 703+/-2 813,
      allP>0.05). (3)Comparing the fluid volume (ml) used for fluid replacement period,
      except that there was no significance in fluid challenge with colloid during 0-6
      hours between two groups [ml: 250 (125, 500) vs. 250 (69,250), P>0.05], more
      fluid intake (ml) was found in ITBVI group [0-6 hours crystalloid: 250(150,250)
      vs. 125 (105,125), 6-72 hours crystalloid: 125 (125, 250) vs. 100 (56, 125), 0-72
      hours crystalloid: 250(125, 250) vs. 125 (75, 125), 6-72 hours colloid: 125 (106,
      250) vs. 75 (50, 125), 0-72 hours colloid: 200 (125, 250) vs. 100 (50, 125),all
      P<0.01]. CONCLUSION: Clinical picture in patients with septic shock is improved
      after 3 days of treatment than 1 day of treatment under fluid management directed
      by ITBVI, compared with by CVP. This improvement may be attributable to accurate
      assessment of preload and appropriate infusion rate in fluid challenge.

PMID- 21878169
TI  - [The prognostic value of N-terminal pro-B-type natriuretic peptide in patients
      with severe sepsis and septic shock].
AB  - OBJECTIVE: To evaluate the prognostic value of N-terminal pro-B-type natriuretic
      peptide (NT-proBNP) in patients with severe sepsis and septic shock. METHODS: In
      a prospective study, clinical data of 50 patients with severe sepsis and septic
      shock were analyzed. Plasma NT-proBNP level was measured at 0, 24, 48 and 72
      hours after admission to the intensive care unit (ICU) of a university hospital.
      Patients were divided into survival group and non-survival group according to 30
      day mortality rate. The dynamic variation of plasma NT-proBNP level was observed
      and the difference of plasma NT-proBNP levels between two groups was compared.
      The predictive value of NT-proBNP on mortality was evaluated by receiver
      operating characteristic (ROC) curves. The potential confounding factors on NT
      proBNP were assessed with linear regression analysis. RESULTS: NT-proBNP levels
      (MUg/L)at 0 hour after admission to ICU [20.86(14.28,23.92)] were significantly
      higher in non-survival group (n=20) compared with survival group [ n=30, 10.02
      (5.58, 16.41), P<0.01], and the difference persisted to 72 hours [19.68 (13.90,
      24.02) vs. 9.24 (4.30, 11.81), P<0.01], but there was no statistical difference
      of NT-proBNP levels among four time points. In the ROC curves for NT-proBNP at
      admission, the area under the curve(AUC) for hospital mortality was 0.842, and
      95% confidence interval (CI) was 0.764-0.922, P<0.01. NT-proBNP greater than
      13.30 MUg/L at admission was an independent indicator of mortality (sensitivity
      80.6%, specificity 70.2%). Linear regression analysis revealed that the
      oxygenation index (PaO(2)/FiO(2), r=-0.839, P=0.003), platelet count (PLT, r=
      0.803, P=0.032), and sequential organ failure assessment (SOFA) scores at 0 hour
      after admission to ICU (r=0.874, P<0.001) had independent effects on NT-proBNP
      values at admission. CONCLUSION: Plasma NT-proBNP level is a valuable prognostic
      factor for severe sepsis and septic shock patients.

PMID- 21878170
TI  - [The effects of administration of valproic acid on organ function and outcome in
      a canine lethal hemorrhagic shock model].
AB  - OBJECTIVE: To investigate the effects of valproic acid (histone deacetylase
      inhibitor) on visceral function and outcome in a canine lethal hemorrhage model.
      METHODS: Twenty male Beagle canines were subjected to an about 42% of total blood
      volume loss to reproduce a lethal hemorrhage shock model. Animals were randomly
      divided into shock control group (SC group) and valproic acid treatment group
      (VPA group), each group n=10. Canines in SC group and VPA group were
      intravenously injected either 20 ml saline or valproic acid (100 mg/kg) in 20 ml
      saline 1.5 hours after hemorrhage. Canines in each group were given delayed
      intravenous fluid resuscitation 24 hours after bleeding. The mean arterial
      pressure (MAP) was measured at 0 hour and at different time points without
      anesthesia, and the plasma levels of alanine aminotransferase (ALT), creatinine
      (Cr) and isoenzyme of creatine kinase (CK-MB) were measured before hemorrhage (0
      hour), and at different time points after hemorrhage. Urinary output and survival
      rate 72 hours after hemorrhage were also recorded. RESULTS: The levels of MAP in
      both groups were significantly lowered from 2 hours after bleeding. The level of
      MAP (mm Hg, 1 mm Hg=0.133 kPa) in VPA group recovered rapidly and exceeded with
      statistically significant difference compared with those of SC group after
      hemorrhage (4 hours: 58.4+/-7.6 vs. 40.3+/-5.0, 8 hours: 84.4+/-8.0 vs. 56.4+/
      4.4, 24 hours: 92.6+/-10.3 vs. 72.6+/-8.9, P<0.05 or P<0.01). The amount of
      urinary output of VPA group was significantly higher than that of SC group during
      the period of 0-8 hours, 8-24 hours, 24-48 hours, and 48-72 hours, but it was
      still lower than that before hemorrhage (0 hour). The plasma parameters for
      visceral function in both groups were significantly elevated compared with 0
      hour. The plasma levels of ALT, Cr and CK-MB in VPA group were obviously lower
      than those in SC group from 4 hours after hemorrhage [at 4 hours after bleeding,
      ALT (U/L): 80.1+/-9.8 vs. 112.2+/-10.1, Cr (MUmol/L): 74.5+/-8.3 vs. 88.0+/-7.6,
      CK-MB (kU/L): 10.39+/- 1.10 vs. 13.67+/-1.46, P<0.05 or P<0.01], but the visceral
      functional parameters at 72 hours after hemorrhage in VPA group were obviously
      higher than those at 0 hour [ALT (U/L):79.5+/-7.1 vs. 40.5+/-4.4; Cr (MUmol/L):
      85.6+/-7.1 vs. 46.6+/-4.8; CK-MB (kU/L): 7.63+/-0.86 vs. 1.66+/-0.21, all
      P<0.01]. The survival rate of VPA group 72 hours after bleeding was significantly
      higher than that of SC group [70% (7/10) vs. 20% (2/10), P<0.05]. CONCLUSION: The
      results indicate that intravenous injection of VPA promote MAP, increase urinary
      output, alleviate visceral injury and improve the survival rate at 72 hours in
      canines suffering from 42% blood volume loss, it might be an effective drug for
      hypovolemic shock, especially in war or other site of mass casualties in an
      austere environment.

PMID- 21878171
TI  - [The level and clinical significance of Toll-like receptor 4 in children with
      severe sepsis].
AB  - OBJECTIVE: To study the clinical significance of Toll-like receptor 4 (TLR4) in
      children with severe sepsis. METHODS: A prospective control study was performed.
      All cases were enrolled from pediatric department of the First Affiliated
      Hospital of Guangzhou Medical College, and they were divided into severe sepsis
      group (14 patients) who were diagnosed to have severe sepsis or septic shock in
      intensive care unit (ICU), pneumonia group (10 cases) with diagnosis of bronchial
      pneumonia, and healthy control group (10 healthy children). Venous blood samples
      of 2 ml were collected at admission, the level of TLR4 was detected by flow
      cytometry .At the same time, the changes in serum interleukin (IL-6, IL-10 ) and
      tumor necrosis factor-alpha (TNF-alpha) levels were determined by enzyme linked
      immunoadsorbent assay (ELISA). RESULTS: In severe sepsis group, the contents of
      TLR4 [(71.56+/-15.32)%], IL-6 [(1.98+/-1.55) ng/L], IL-10 [(88.20+/-61.23) ng/L]
      and TNF-alpha [(104.08+/-85.36) ng/L] were significantly higher than those in
      pneumonia group [(50.07+/-26.36)%, (0.93+/-0.16) ng/L, (41.42+/-7.02) ng/L,
      (48.96+/-6.40) ng/L] and healthy control group [(39.43+/-17.43)%, (0.94+/-0.43)
      ng/L,(43.73+/-22.68) ng/L, ( 49.94+/- 18.47) ng/L, all P<0.05). But there was no
      significant difference in the contents of TLR4, IL-6, IL-10 and TNF-alpha between
      pneumonia group and healthy control group (all P>0.05). CONCLUSION: This study
      suggests that TLR4 might be critically involved in the development of sepsis, and
      changes in TLR4 expression are parallel with levels of proinflammatory cytokines,
      including IL-6, TNF-alpha, and IL-10. The combination of TLR4 and proinflammatory
      cytokines would serve as the predictive parameters in early diagnosis and
      severity evaluation of sepsis in children.

PMID- 21878172
TI  - [Dynamic changes in plasma levels of urokinase type plasminogen activator and
      urokinase type plasminogen activator receptor in patients with systemic
      inflammatory response syndrome].
AB  - OBJECTIVE: To study the dynamic changes in plasma levels of urokinase type
      plasminogen activator (uPA) and urokinase type plasminogen activator receptor
      (uPAR) and their influence on prognosis in patients with systemic inflammatory
      response syndrome (SIRS). METHODS: In this study, a prospective clinical case
      control study was adopted. Eighty-five patients were divided into two groups
      according to diagnostic criteria of SIRS: SIRS patients (n=50) and non-SIRS
      patients (n=35). SIRS patients were again divided into SIRS group (n=26) and SIRS
      complicated by multiple organ dysfunction syndrome (MODS) group (n=24) by their
      severity, and survival group (n=35) and non-survival group (n=15) by their
      outcome . The control group comprised of 30 healthy blood donors. Venous blood
      samples of about 2 ml were collected at the time when non-SIRS patients were
      admitted, and blood samples were collected in SIRS patients on 1,3, 5 and 7 days
      when SIRS was diagnosed, and in the healthy control group blood samples were
      collected when they visited the General Health Check-up Division at our hospital.
      Plasma levels of uPA and uPAR were measured by enzyme-linked immunosorbent assay
      (ELISA), and relationship between plasma level of uPAR and acute physiology and
      chronic health evaluation II(APACHEII) score was analyzed using Pearson
      correlation. RESULTS: The plasma levels of uPA and uPAR in patients of SIRS and
      MODS were obviously higher compared with non-SIRS and healthy controls [uPA
      (MUg/L): 1.208+/-0.264, 1.120+/-0.276 vs. 0.744+/-0.190, 0.782+/-0.257; uPAR
      (MUg/L): 3.704+/-1.018, 4.970+/-1.284 vs. 1.892+/-0.476, 1.823+/- 0.797, all
      P<0.01]. The plasma level of uPAR in MODS group was obviously higher than that of
      SIRS group (P<0.01). The plasma level of uPA (MUg/L) in non-survival group was
      markedly elevated on 5 days and 7 days compared to survival group (5 days:
      1.177+/-0.185 vs. 0.856+/-0.223, 7 days: 1.377+/-0.185 vs. 0.836+/-0.223, both
      P<0.01). The plasma level of uPAR (MUg/L) in patients of non-survival group was
      obviously higher compared with survival group on 1, 3, 5 and 7 days (1 day:
      5.301+/-1.410 vs. 3.888+/-1.015, 3 days: 4.017+/-0.898 vs. 2.994+/-0.638, 5 days:
      5.032+/-1.238 vs. 2.536+/-1.017, 7 days: 5.232+/-1.238 vs. 3.536+/-1.017, all
      P<0.01). Correlation analysis showed that there was positive correlation between
      uPAR level and APACHEII score (r=0.640, P<0.01). CONCLUSION: Coagulopathy is
      present in SIRS patients, the plasma levels of uPA and uPAR are high in patients
      with SIRS, and the increase of uPAR in patients with SIRS indicates a poor
      prognosis.

PMID- 21878173
TI  - [Induction of expression of von Willebrand factor cleaving protease of rat aortic
      endothelial cell by lipopolysaccharide challenge].
AB  - OBJECTIVE: To investigate the dose response effect and time response effect of
      lipopolysaccharide(LPS) on von Willebrand factor cleaving protease (ADAMTS-13,
      Vwf-cp) mRNA expression and protein in rat aortic endothelial cells (RAECs).
      METHODS: RAECs were grown by culturing of aortic tissue. When ARECs were cultured
      for one week, it was co-cultured by 1:3 to reach 4-5 generations. ARECs were
      randomly divided into five groups: control group and four LPS stimulation groups
      (0.01, 0.1, 1 and 5 MUg/ml) . The RAECs and supernatants were obtained at 12, 24,
      48, and 72 hours after being stimulated by LPS. ADAMTS-13 mRNA expression of
      RAECs was assessed by quantitation reverse transcription-polymerase chain
      reaction (RT-PCR), and protein of ADAMTS-13 in supernatants was determined by
      enzyme linked immunoadsorbent assay (ELISA). RESULTS: In the control group RAECs
      were shown to express ADAMTS-13 at both protein and mRNA levels. With the
      increase of concentration of LPS, or increase in stimulus duration, expression of
      ADAMTS-13 mRNA and protein were gradually lowered. Compared with the control
      group (25.22 +/-1.41), the level of ADAMTS-13 mRNA in 0.01 MUg/ml LPS stimulation
      group was markedly decreased at 48 hours (18.78+/-0.86, P<0.01). At 24 hours, the
      levels of ADAMTS-13 mRNA (23.43+/-0.63, 22.41+/-0.76) were markedly decreased in
      0.1 MUg/ml and 1 MUg/ml LPS stimulation groups (P<0.05 and P<0.01). The level of
      ADAMTS-13 mRNA (20.01+/-2.47) in 5 MUg/ml LPS stimulation group was markedly
      decreased at 12 hours (P<0.01). Compared with the control group [(115.76+/-2.36)
      ng/ml], protein level of ADAMTS-13 [(113.43+/-1.07) ng/ml] was markedly decreased
      at 12 hours in 0.01 MUg/ml LPS stimulation group (P<0.05). The protein level of
      ADAMTS-13 [(7.63+/-2.64) ng/ml] was lowest in 5 MUg/ml LPS stimulation group at
      72 hours (P<0.01). CONCLUSION: Normal RAECs can express ADAMTS-13 at both mRNA
      and protein to certain extent. The expression of ADAMTS-13 mRNA and protein are
      decreased after LPS challenge in different concentrations for different duration
      in dose dependent and time dependent manner.

PMID- 21878174
TI  - [Effect of Buyang Huanwut decoction on apoptosis of splenocytes in rats with
      sepsis].
AB  - OBJECTIVE: To observe the change in number of spleen T lymphocyte, B lymphocyte,
      apoptotic splenocytes and the expression of Bcl-2 and Bax protein in rats with
      sepsis; to study the effect of Buyang Huanwu decoction (BYHWD) on the immune
      function in rats with sepsis. METHODS: One hundred and eighty healthy male Wistar
      rats were randomly divided into four groups: sham operation group (n=30), model
      group (n=50), BYHWD treatment group (n=50) and BYHWD prevention group (n=50) .
      Sepsis model was reproduced by cecal ligation and puncture (CLP). The rats of
      BYHWD treatment group and BYHWD prevention group were given BYHWD (1 g/ml) 15
      ml/kg at 30 minutes after surgery, and 3 days before surgery, once a day,
      respectively. The rats were sacrificed and their spleens were harvested at 6, 12,
      24, 48, 96 hours after reproduction of the model. Morphological changes in
      spleen, the expression of T lymphocyte, B lymphocyte, apoptotic cells, Bcl-2 and
      Bax were determined in all the groups. RESULTS: By light microscopy, it was found
      that white pulp became atrophic and splenic nodules destroyed after CLP. The
      pathology was most obvious in model group, followed by BYHWD treatment group, and
      least obvious in prevention group. CD4(+) T lymphocyte, CD40 B lymphocyte and Bcl
      2 protein expression in model group were obviously reduced compared with those of
      sham operation group, but the number of apoptotic cells and Bax protein
      expression were elevated, reaching their nadir or peak 24 hours after the surgery
      [the optical densities (A value): CD4(+) T lymphocyte: 18.28+/-4.57 vs. 98.60+/
      18.18; CD40 B lymphocyte: 26.96+/-6.26 vs. 104.87+/-30.97; Bcl-2 protein
      expression: 20.23+/-11.75 vs. 149.67+/-5.24; apoptotic cells: 241.75+/-44.79 vs.
      14.67+/-5.24; Bax protein expression: 128.75+/-44.79 vs. 5.34+/-4.26, all
      P<0.01], then they gradually increase or decrease. CD8(+) T lymphocyte count did
      not significantly changed . The results showed that BYHWD could markedly elevate
      the level of CD4(+) T lymphocyte and CD40 B lymphocyte, and lower the protein
      expression of apoptotic cells and Bax. There were no significant changes in the
      CD8(+) T lymphocyte and Bcl-2 protein expression. Furthermore, the results in the
      BYHWD prevention group were better than those in BYHWD treatment group (A value:
      CD4(+) T lymphocyte: 94.12+/-15.45 vs. 72.37+/-8.00; B lymphocyte: 90.46+/-13.34
      vs. 55.66+/-4.23; apoptotic cells: 27.63+/-9.91 vs. 40.83+/-16.09; Bax protein
      expression: 11.63+/-5.91 vs. 30.83+/-16.09, P<0.05 or P<0.01). Ninety-six hours
      after CLP, the above indexes gradually approached to the level of the sham
      operation group. Correlation analysis showed that cell apoptosis and Bax were
      positively correlated (r=0.522, P=0.000), but cell apoptosis and Bcl-2 showed
      negative correlation (r=-0.659, P=0.000). CONCLUSION: BYHWD improves the
      immunological suppression in rats with sepsis by lowering apoptosis of CD4(+) T
      lymphocyte and B lymphocyte in spleen, and its underlying mechanism may be that
      BYHWD produce a decrease of apoptosis through Bax.

PMID- 21878175
TI  - [The effect of ulinastatin on gene expression of brain tissue in septic rat].
AB  - OBJECTIVE: To detect the differences in gene expression of brain tissue in septic
      rats with ulinastatin (UTI) preconditioning with DNA microarray. METHODS: Forty
      five male Wistar rats were equally divided into control group, sepsis group, and
      UTI group by means of random number table. In UTI group the rats were treated
      with intramuscular injection of UTI (100 kU/kg) 1 hour before cecal ligation and
      puncture (CLP). In sepsis group and control group intramuscular balanced solution
      (5 ml/kg) instead of UTI was given. Septic rat model was reproduced by CLP. The
      control group underwent a simulated operation without CLP. Gene expression
      profile was studied by using RatRef-12 rat gene expression profile microarray to
      detect the changes in gene expression pattern of rat brain tissue after CLP. Then
      related computer software was used to screen and analyze the relationship between
      the sepsis/UTI group and control group. Finally, the difference between the
      sepsis group and UTI group was analyzed. RESULTS: In 22 523 genes, 55
      differential genes were found between sepsis group and control group, accounting
      for 0.244%. Among them 47 genes showed down-regulation, with 23 known functional
      genes; 8 genes showed up-regulation, with 6 known functional genes. Eighty-two
      differential genes were found between UTI group and control group, accounting for
      0.364%. Among them 66 genes showed down-regulation, with 39 known functional
      genes; 16 genes showed up-regulation, with 8 known functional genes. When sepsis
      group and UTI group compared with control group, 19 genes showed the same degree
      of regulation,with 18 genes (Adora2a, Avp, Cart, Gng7, Myh7, Oxt, Pde1b, Pdyn,
      Prkcd, Prkch, Rgs9, Rxrg, Six3, Slc17a6, Slco1a5, Sostdc1, Tac1, Ttr) showed down
      regulation and 1 gene (S100a8) showed up-regulation. CONCLUSION: UTI
      preconditioning can partly adjust abnormal expression of genes in the brain
      tissue of rat with sepsis in the presence of excessive inflammation and immune
      suppression. UTI has some degree of protective effect on brain at the genetic
      level. Meanwhile, there is certain self regulation in the body during sepsis.

PMID- 21878176
TI  - [Preliminary investigation of risk stratification and prognosis of B-type brain
      natriuretic peptide in patients with sepsis].

PMID- 21878180
TI  - [Advances in the study of platlets and neutrophils in sepsis].

PMID- 21878181
TI  - [The progression of betaadrenergic modulation in sepsis].

PMID- 21878182
TI  - [The stage-biomarkers of the sepsis].

PMID- 21878183
TI  - Traditional food and monetary access to market-food: correlates of food
      insecurity among Inuit preschoolers.
AB  - OBJECTIVES: To evaluate correlates of food insecurity among Inuit preschoolers.
      Study design. Cross-sectional health survey. METHODS: Correlates of food
      insecurity were assessed in 3-5 year old children (n=388) residing in 16 Nunavut
      communities (2007-2008) in whom a high prevalence of child food insecurity (56%)
      has been documented. A bilingual team conducted interviews, including 24-hour
      dietary recalls and past-year food security assessment involving monetary access
      to market foods. RESULTS: Children residing in child food insecure homes were
      more likely to have consumed traditional food (TF) (51.7% vs. 39.9%, p <= 0.01),
      and less likely to have consumed any milk (52.2% vs. 73.2%, p <= 0.001) compared
      to children in child food secure homes. Median healthy eating index scores were
      significantly lower (77.1 vs. 79.9, p <= 0.01) and sugar drink intake higher (429
      vs. 377 g/day, p <= 0.05) in children from child food insecure than food secure
      households. Children that consumed TF had higher protein and lower carbohydrate
      intake (p <= 0.05) and tendencies for a lower prevalence of iron deficiency
      (plasma ferritin <12 MUg/l; p <= 0.10) regardless of food security status. A
      borderline significant interaction of TF by food security status (p <= 0.10) was
      observed where the percent of anemia (hemoglobin <110 and <115 g/l for 3-4 and 5
      yr. olds, respectively) was highest among children from child food insecure homes
      who consumed no TF. CONCLUSIONS: TF and market food contribute to food security
      and both need to be considered in food security assessments. Support systems and
      dietary interventions for families with young children are needed.

PMID- 21878184
TI  - Developing effective, culturally appropriate avenues to FASD diagnosis and
      prevention in northern Canada.
AB  - This article describes 2 research initiatives that are being undertaken by
      members of the Canada Northwest FASD Research Network, involving collaborations
      between researchers, clinicians, service providers and community members in the
      Canadian North. Improving both the diagnosis and prevention of FASD requires
      evidence-based approaches to clinical and social service delivery that are
      capable of accounting for the unique contours of the geographic, regional and
      cultural diversities in which women become pregnant and in which families live.
      Although FASD has been a priority for communities and governments in northern
      Canada, research capacity has not been available to support the development of
      the context-specific knowledge needed to inform policy and practice in this
      region. Moreover, there have not been adequate mechanisms for transferring
      practice-based knowledge from the Canadian North to researchers and service
      providers in the South, who might make use of this knowledge to inform their own
      practice. Herein, we highlight the ways in which reciprocal knowledge exchange
      involving CanFASD Northwest researchers at academic health science centres and
      diverse stakeholder groups is supporting multi-directional capacity building in
      FASD diagnosis and prevention.

PMID- 21878185
TI  - Survey of "northern" child and maternal health research being conducted in
      Canada.
AB  - OBJECTIVES: The purpose of the study is to better understand the scope of
      research being conducted by Canadian paediatric and maternal health centres on
      the topic of maternal child health of northern populations. In addition, the
      results are intended to help assess the prospects for the creation of a research
      network dedicated to this topic. STUDY DESIGN: Questionnaire study complemented
      with review of database. METHODS: Data were collected using a short questionnaire
      with qualitative and quantitative questions. Surveys were sent by email to
      members of two Canadian national paediatric groups, representing 17
      organizations. Supplementary information was obtained through review of the
      database for research funded by the Canadian Institutes of Health Research (CIHR)
      and by the International Polar Year Program. RESULTS: Response was limited, with
      most input coming from academic environments with a strong commitment to research
      conducted among northern populations. Research focuses included health as well as
      other disciplines. The definition of "the North" provided by respondents fit
      generally within the operational definition identified by the researchers.
      CONCLUSIONS: The topic of maternal and child health is more thoroughly examined
      among rural and remote populations than specifically among northern populations.
      The existence of a type of network, the evidence of a lack of inter-institutional
      communication and the identified need for support lead to the conclusion that a
      formal research network would be of benefit. Research is already funded by
      national funding agencies, suggesting that there may be an opportunity to
      collaborate with a national agency in the development of an appropriate network.

PMID- 21878186
TI  - Treatment of nephrotic syndrome with adrenocorticotropic hormone (ACTH).
AB  - Over the last two decades, adrenocorticotropic hormone (ACTH) has re-emerged as a
      potentially effective therapy for nephrotic syndrome, particularly for patients
      who have failed more conventional immunosuppressive therapies. The initial
      experience in Europe using synthetic ACTH in membranous nephropathy led to a
      randomized trial in which ACTH performed comparably to a combined regimen of
      steroids and alkylating agents. Observational data from American patients treated
      with natural ACTH gel for resistant nephrotic syndrome have also been promising.
      While we await larger clinical trials of ACTH in the nephrotic patient
      population, we still also await a more precise understanding of how the therapy
      achieves remission of proteinuria. We discuss a number of possible mechanisms for
      ACTH's beneficial effects on the inflammation and injury that occurs in nephrotic
      syndrome.

PMID- 21878187
TI  - Oligonucleotides decoy to NF-kappaB: becoming a reality?
AB  - In the last two decades, frontiers in new drug development are represented by
      genetic code inhibitors. Nuclear factor-kappaB (NF-kappaB) is a transcription
      factor playing critical roles in many inflammatory/immune diseases. Decoy
      oligonucleotides (decoy ONs) epitomize an ideal pharmacological tool to
      selectively block NF-kappaB activation. Their use is currently being investigated
      in several chronic inflammatory-based diseases. However, decoy ONs' clinical use
      is strongly hampered by several issues. Chemical modifications and/or delivery
      systems have been investigated to overcome some of these limits. This review
      describes the successful preclinical and clinical applications of decoy ON
      against NF-kappaB in inflammatory-based diseases.

PMID- 21878188
TI  - New insights into p53 based therapy.
AB  - A common step in human cancer is the inactivation of the p53 tumor suppressor
      pathway. This occurs either by mutations in the coding region of the p53 gene
      itself, or equally commonly, by inactivation of pathways that are required for
      p53 to exert its cellular function. Dramatic new results from animal models and
      the widespread availability of p53 activating small molecules are yielding
      important new insights into the therapeutic and toxic effects of p53 and how
      these can be exploited for improving therapy of cancer and other diseases.

PMID- 21878190
TI  - Functional effects of susceptibility genes in osteoarthritis.
AB  - Osteoarthritis is the most common chronic musculoskeletal disorder. Although
      osteoarthritis is a multifactorial disease, it is known to have a significant
      genetic contribution. Identified genes so far, contributing to the prevalence and
      progression of the disease, belong to signaling pathways such as the bone
      morphogenetic protein and the wingless-type signaling families. These pathways
      are important during development and appear to be reactivated in postnatal joint
      homeostasis and repair. Among the most consistently associated genes, so far, are
      GDF5 and FRZB, which were both originally identified from a chondrogenic extract
      of articular cartilage. We focus on the functional aspects of these
      susceptibility genes and summarize recent evidence, obtained in specific animal
      models, for their possible roles in osteoarthritis. These data support the view
      that all tissues within the joint may contribute to osteoarthritis and that
      pathways important in skeletal development are also involved in the disease
      processes thereby presenting attractive therapeutic targets.

PMID- 21878191
TI  - Combining SERCA2a activation and Na-K ATPase inhibition: a promising new approach
      to managing acute heart failure syndromes with low cardiac output.
AB  - Heart failure (HF) patients are a medically complex and heterogeneous population
      with multiple cardiac and non-cardiac comorbidities. Although there are a
      multitude of etiologic substrates and initiating and amplifying mechanisms
      contributing to disease progression, these pathophysiologic processes ultimately
      all lead to impaired myocardial function. The myocardium must both pump
      oxygenated, nutrient-rich blood throughout the body (systolic function) and
      receive deoxygenated, nutrient-poor blood returning from the periphery (diastolic
      function). At the molecular level, it is well-established that Ca2+ plays a
      central role in excitation-contracting coupling with action potentials
      stimulating the opening of L-type Ca2+ in the plasma membrane and ryanodine
      receptor 2 (RyR2) in the sarcoplasmic reticulum (SR) membrane during systole and
      the Na-Ca2+ exchanger and SERCA2a returning Ca2+ to the extracellular space and
      SR, respectively, during diastole. However, there is increasing recognition that
      impaired Ca2+ cycling may contribute to myocardial dysfunction. Preclinical
      studies and clinical trials indicate that combining SERCA2a activation and Na-K
      ATPase inhibition may increase contractility (inotropy) and facilitate active
      relaxation (lusitropy), improving both systolic and diastolic functions.
      Istaroxime, a novel luso-inotrope that activates SERCA2a and inhibits the Na-K
      ATPase, is currently in phase II clinical development and has been shown to
      improve systolic and diastolic functions and central hemodynamics, increase
      systolic but not diastolic blood pressure, and decrease substantially heart rate.
      Irrespective of its clinical utility, the development of istaroxime has evolved
      our understanding of the clinical importance of inhibiting the Na-K ATPase in
      order to obtain a clinically significant effect from SERCA2a activation in the
      setting of myocardial failure.

PMID- 21878189
TI  - T cell costimulation and coinhibition: genetics and disease.
AB  - T cell costimulatory and coinhibitory pathways are essential orchestrators and
      regulators of the adaptive immune response. In recent years, the costimulatory
      CD28 receptor and B7 ligand families have been expanded to include a total of
      four and seven members, respectively. Several polymorphisms, mutations, and
      deletions in both regulatory and protein-coding regions of these genes have
      subsequently been discovered and evaluated for genetic linkage to various human
      diseases. Here, we review this evidence as we discuss T cell costimulation and
      coinhibition in the context of genetic susceptibility to autoimmunity, cancer,
      and other diseases. As we gain further insight into the functional significance
      and mechanism of these immunoregulatory pathways by both genetic and
      immunological approaches, these receptors and ligands are poised to become key
      targets for immunotherapy.

PMID- 21878192
TI  - Specificity of the coxsackievirus B4 VP4 capsid protein investigated in silico.
AB  - The Enterovirus genus encompasses several species and various serotypes, like
      coxsackievirus-B1 (CV-B1) to CV-B6, and many variants. The role of these viruses,
      especially CV-B4, in the pathogenesis of type 1 diabetes is strongly suspected.
      It has been reported that antibodies directed towards the region of amino acids
      11-30 of the VP4 capsid protein enhance the infection of human peripheral blood
      mononuclear cells with CV-B4. In order to predict the inter- and intra-serotype
      specificity of the region 11-30 of CV-B4 VP4, 362 available protein sequences of
      CV-B1 to -B6, CV-A9, and swine vesicular disease virus (SVDV) have been aligned
      and levels of homology have been calculated. Serine residue substitutions in this
      region of VP4 were observed without predictable subsequent modification of
      conformation or charge. The amino acids 16-24 region was the most variable. The
      sequence of amino acids 16-24 of the CV-B4E2 VP4 protein was highly homologous to
      those of other CV-B4 (64.4%) whereas there was no homology with CV-B3 and B5 and
      very low levels of homology with CV-B1 and B2 (3.3% and 9.9%, respectively). In
      conclusion, the bioinformatic analysis suggests that the region 16-24 of the VP4
      capsid protein is the feature of the specificity of the target of infection
      enhancing antibodies directed towards CV-B.

PMID- 21878193
TI  - Pharmacogenomics in ophthalmology.
AB  - Inter-individual variation in drug response and adverse drug reactions (ADRs) are
      well known in medicine. This individual variation in drug response could be at
      least, in part, due to genetic diversity among individuals. Although substantial
      studies that connect genetic variants to inter-individual variation in drug
      response have been documented in several diseases such as cancer and heart
      diseases, such studies are slowly progressing in ophthalmology. In recent years,
      advancement in technologies has led to the identification of genes associated
      with several eye disorders. At the same time, some small-scale studies have
      demonstrated the association of various genotypes or haplotypes with response to
      drug therapies. However, its integration into clinical practice in ophthalmology
      is not possible at present. This is because there are many challenging questions
      that remain to be addressed. For instance, in the case of complex disorders a
      single gene study is not enough. Multiple genes, environmental factors, multiple
      single nucleotide polymorphisms (SNPs), and rare or low frequency variants may
      contribute to the disease and they must be considered. The functional aspects of
      many genetic variants are not known. This raises questions of their biological
      importance and their clinical usefulness. In addition, there are legal, ethical,
      and social issues that need to be regulated. Moreover, physicians and patients
      must be educated about the limitation and sensitivity of genetic testing. At
      present pharmacogenetic studies in ophthalmology are still in their infancy and
      do not suggest that a pharmacogenetic basis of drug development in ophthalmology
      is a concept that can yield immediate results, but can become a reality in the
      future. In this article an attempt has been made to summarize some of the recent
      small-scale pharmacogenetic studies on two major eye disorders, age-related
      macular degeneration (AMD) and glaucoma.

PMID- 21878194
TI  - Words of wisdom. Re: Comorbidity and mortality results from a randomised prostate
      cancer screening trial.

PMID- 21878195
TI  - Words of wisdom. Re: Association of statin use with pathological tumor
      characteristics and prostate cancer recurrence after surgery.

PMID- 21878196
TI  - Words of wisdom. Re: Radical prostatectomy versus watchful waiting in early
      prostate cancer.

PMID- 21878197
TI  - Words of wisdom. Re: Impact of posterior musculofascial reconstruction on early
      continence after robot-assisted radical prostatectomy: results of a prospective
      parallel group trial.

PMID- 21878198
TI  - Words of wisdom. Re: International phase III trial assessing neoadjuvant
      cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder
      cancer: long-term results of the BA06 30894 trial.

PMID- 21878199
TI  - Words of wisdom. Re: Abiraterone and increased survival in metastatic prostate
      cancer.

PMID- 21878200
TI  - Nonsteroidal anti-inflammatory drugs and statins have chemopreventative effects
      in patients with Barrett's esophagus.
AB  - BACKGROUND & AIMS: The incidence of Barrett's esophagus and esophageal
      adenocarcinoma has increased despite surveillance of patients with Barrett's
      esophagus. Limited data indicate that nonsteroidal anti-inflammatory drug (NSAID)
      and statin use reduce the risk for esophageal adenocarcinoma. We investigated
      whether NSAID or statin use reduces the risk of neoplastic progression from
      Barrett's esophagus. METHODS: We performed a prospective study of 570 patients
      with Barrett's esophagus at 3 academic and 12 regional Dutch hospitals.
      Information on medication use was collected in patient interviews at each
      surveillance visit and cross-checked with pharmacy records. Patients completed a
      questionnaire about use of over-the-counter medication. Incident cases of high
      grade dysplasia and adenocarcinoma were identified during the follow-up period.
      RESULTS: During a median follow-up period of 4.5 years, 38 patients (7%)
      developed high-grade dysplasia or adenocarcinoma. After Barrett's esophagus had
      been diagnosed, 318 patients (56%) used NSAIDs for a median duration of 2 months,
      161 (28%) used aspirin for a median duration of 5 years, 209 (37%) used statins
      for a median duration of 5 years, and 107 (19%) used NSAIDs and statins. NSAID
      and statin use were each associated with a reduced risk of neoplastic progression
      (hazard ratio [HR], 0.47; P = .030 and HR, 0.46; P = .048, respectively). Use of
      a combination of NSAIDs and statins increased the protective effect (HR, 0.22; P
      = .028). CONCLUSIONS: NSAID and statin use reduce the risk of neoplastic
      progression in patients with Barrett's esophagus. Use of a combination of NSAIDs
      and statins appears to have an additive protective effect.

PMID- 21878201
TI  - Claudin-1 up-regulates the repressor ZEB-1 to inhibit E-cadherin expression in
      colon cancer cells.
AB  - BACKGROUND & AIMS: Expression of the tight junction protein claudin-1 is
      dysregulated in colon tumors and associates with their progression. Up-regulation
      of claudin-1 reduces expression of E-cadherin. We investigated the mechanisms by
      which claudin-1 regulates E-cadherin expression and its effects in colon cancer
      cells. MATERIALS AND METHODS: We used gene expression analysis, immunoblotting,
      and reverse transcription polymerase chain reaction to associate expression of
      the repressor of transcription Zinc Finger E-box binding homeobox-box1 (ZEB-1)
      with claudin-1. We analyzed SW480 colon cancer cells that overexpressed claudin
      1, or SW620 cells in which claudin-1 expression was repressed, to determine the
      effects on ZEB-1 and E-cadherin expression, invasive activity, and resistance to
      anoikis. We studied cells that expressed constitutively active or dominant
      negative forms of factors in the Wnt or phosphotidylinositol-3-kinase signaling
      pathways and used pharmacologic inhibitors of these pathways to study their role
      in claudin-1-dependent regulation of ZEB-1. We used microarray analysis to
      examine gene expression patterns in 260 colorectal tumor and normal colon
      samples. RESULTS: Claudin-1 down-regulates E-cadherin expression by up-regulating
      expression of ZEB-1. Claudin-1 activates Wnt and phosphotidylinositol-3
      kinase/Akt signaling. ZEB-1 mediates claudin-1-regulated changes in cell invasion
      and anoikis. Expression of claudin-1 correlated with that of ZEB-1 in human colon
      tumor samples. In the progression from normal colonic epithelium to colon
      adenocarcinoma, levels of E-cadherin decreased, whereas levels of claudin-1 and
      ZEB-1 increased. Down-regulation of E-cadherin and up-regulation of ZEB-1 in
      colon tumors were associated with shorter survival times. CONCLUSIONS: Claudin-1
      up-regulates the repressor ZEB-1 to reduce expression of E-cadherin in colon
      cancer cells, increasing their invasive activity and reducing anoikis. This
      pathway is associated with colorectal cancer progression and patient survival.

PMID- 21878202
TI  - Loss of caspase-8 protects mice against inflammation-related hepatocarcinogenesis
      but induces non-apoptotic liver injury.
AB  - BACKGROUND & AIMS: Disruption of the nuclear factor-kappaB (NF-kappaB) essential
      modulator (NEMO) in hepatocytes of mice (NEMO(Deltahepa) mice) results in
      spontaneous liver apoptosis and chronic liver disease involving inflammation,
      steatosis, fibrosis, and development of hepatocellular carcinoma. Activation of
      caspase-8 (Casp8) initiates death receptor-mediated apoptosis. We investigated
      the pathogenic role of this protease in NEMO(Deltahepa) mice or after induction
      of acute liver injury. METHODS: We created mice with conditional deletion of
      Casp8 in hepatocytes (Casp8(Deltahepa)) and Casp8(Deltahepa)NEMO(Deltahepa)
      double knockout mice. Acute liver injury was induced by Fas-activating
      antibodies, lipopolysaccharides, or concanavalin A. Spontaneous
      hepatocarcinogenesis was monitored by magnetic resonance imaging. RESULTS:
      Hepatocyte-specific deletion of Casp8 protected mice from induction of apoptosis
      and liver injury by Fas or lipopolysaccharides but increased necrotic damage and
      reduced survival times of mice given concanavalin A.
      Casp8(Deltahepa)NEMO(Deltahepa) mice were protected against steatosis and
      hepatocarcinogenesis but had a separate, spontaneous phenotype that included
      massive liver necrosis, cholestasis, and biliary lesions. The common mechanism by
      which inactivation of Casp8 induces liver necrosis in both injury models involves
      the formation of protein complexes that included the adaptor protein Fas
      associated protein with death domain and the kinases receptor-interacting protein
      (RIP) 1 and RIP3-these have been shown to be required for programmed necrosis. We
      demonstrated that hepatic RIP1 was proteolytically cleaved by Casp8, whereas
      Casp8 inhibition resulted in accumulation of RIP complexes and subsequent liver
      necrosis. CONCLUSIONS: Inhibition of Casp8 protects mice from
      hepatocarcinogenesis following chronic liver injury mediated by apoptosis of
      hepatocytes but can activate RIP-mediated necrosis in an inflammatory
      environment.

PMID- 21878203
TI  - Ionic mechanism of shock-induced arrhythmias: role of intracellular calcium.
AB  - BACKGROUND: Strong electrical shocks can cause focal arrhythmias, the mechanism
      of which is not well known. Strong shocks have been shown to produce diastolic
      Ca(i)(2+) increase, which may initiate focal arrhythmias via spontaneous
      Ca(i)(2+) rise (SCR), activation of inward Na(+)/Ca(2+) exchange current
      (I(NCX)), and rise in membrane potential (V(m)). It can be hypothesized that this
      mechanism is responsible for generation of shock-induced arrhythmias. OBJECTIVE:
      The purpose of this study was to examine the roles of SCRs and I(NCX) in shock
      induced arrhythmias. METHODS: The occurrence of SCRs during shock-induced
      arrhythmias was assessed in neonatal rat myocyte cultures. RESULTS: Simultaneous
      V(m)-Ca(i)(2+) optical mapping at arrhythmia source demonstrated that V(m)
      upstrokes always preceded Ca(i)(2+) transients, and V(m)-Ca(i)(2+) delays were
      not different between arrhythmic and paced beats (5.5 +/- 0.9 and 5.7 +/- 0.4 ms,
      respectively, P = .5). Shocks caused gradual rise of diastolic Ca(i)(2+)
      consistent with membrane electroporation but no significant Ca(i)(2+) rises
      immediately before V(m) upstrokes. Application of the Ca(i)(2+) chelator BAPTA-AM
      (10 MUmol/L) decreased the duration of shock-induced arrhythmias whereas
      application of the I(NCX) inhibitor KB-R7943 (2 MUmol/L) increased it, indicating
      that, despite the absence of SCRs, changes in Ca(i)(2+) affected arrhythmias. It
      is hypothesized that this effect is mediated by Ca(i)(2+) inhibition of outward
      I(K1) current and destabilization of resting V(m). The possible role of I(K1) was
      supported by application of the I(K1) inhibitor BaCl(2) (0.2 mmol/L), which
      increased the arrhythmia duration. CONCLUSION: Shock-induced arrhythmias in
      neonatal rat myocyte monolayers are not caused by SCRs and inward I(NCX).
      However, these arrhythmias depend on Ca(i)(2+) changes, possibly via Ca(i)(2+)
      dependent modulation of outward I(K1) current.

PMID- 21878204
TI  - Effects of burst-type transcutaneous electrical nerve stimulation on cervical
      range of motion and latent myofascial trigger point pain sensitivity.
AB  - OBJECTIVE: To assess the effects of a burst application of transcutaneous
      electrical nerve stimulation (TENS) on cervical range of motion and pressure
      point sensitivity of latent myofascial trigger points (MTrPs). DESIGN: A single
      session, single-blind randomized trial. SETTING: General community rehabilitation
      clinic. PARTICIPANTS: Individuals (N = 76; 45 men, 31 women) aged 18 to 41 years
      (mean +/- SD, 23 +/- 4y) with latent MTrPs in 1 upper trapezius muscle.
      INTERVENTIONS: Subjects were randomly divided into 2 groups: a TENS group that
      received a burst-type TENS (pulse width, 200 MUs; frequency, 100 Hz; burst
      frequency, 2 Hz) stimulation over the upper trapezius for 10 minutes, and a
      placebo group that received a sham-TENS application over the upper trapezius also
      for 10 minutes. MAIN OUTCOME MEASURES: Referred pressure pain threshold (RPPT)
      over the MTrP and cervical range of motion in rotation were assessed before, and
      1 and 5 minutes after the intervention by an assessor blinded to subjects'
      treatment. RESULTS: The analysis of covariance revealed a significant group *
      time interaction (P < .001) for RPPT: the TENS group exhibited a greater increase
      compared with the control group; however, between-group differences were small at
      1 minute (0.3 kg/cm2; 95% confidence interval [CI], 0.1-0.4) and at 5 minutes
      (0.6 kg/cm2; 95% CI, 0.3-0.8) after treatment. A significant group * time
      interaction (P=.01) was also found for cervical rotation in favor of the TENS
      group. Between-group differences were also small at 1 minute (2.0 degrees ; 95%
      CI, 1.0-2.8) and at 5 minutes (2.7 degrees ; 95% CI, 1.7-3.8) after treatment.
      CONCLUSIONS: A 10-minute application of burst-type TENS increases in a small but
      statistically significant manner the RPPT over upper trapezius latent MTrPs and
      the ipsilateral cervical range of motion.

PMID- 21878205
TI  - Safety of low-dose oral dantrolene sodium on hepatic function.
AB  - OBJECTIVE: To investigate the incidence of hepatobiliary dysfunction after
      administration of low-dose dantrolene sodium. DESIGN: A retrospective survey of
      medical records. SETTING: One secondary and 2 tertiary hospitals. PARTICIPANTS:
      Patients (N=243; 144 men, 27 children; mean age +/- SD, 47.8 +/- 19.7y) who were
      administered dantrolene at a daily dose of 12.5 to 400mg for more than 4 weeks.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Liver function test (LFT)
      results, including serum total bilirubin, aspartate transaminase, alanine
      transaminase, and alkaline phosphatase, were recorded before and at least 1 month
      after the initial dose of dantrolene. In cases of treatment cessation, the reason
      was investigated. Significantly elevated LFT levels were defined as >= to 2 times
      the upper limit of the normal range. RESULTS: Treatment duration was 268.0 +/-
      428.5 days with a daily dose of 65.2 +/- 44.7 mg. At the end of the
      investigation, 95 patients (39.1%) had been lost to follow-up, and 105 (43.2%)
      had stopped treatment. The reasons for cessation were improved spasticity
      (42.9%), no effect of the medication (27.6%), weakness (6.7%), and other medical
      problems (5.7%). Patients with weaknesses did not have elevated LFT values. A 32
      year-old man with head injuries and multiple trauma developed hepatic dysfunction
      82 days after the initial dose and 43 days after a dose increment to 400mg/d.
      Other patients did not experience significant LFT abnormalities. CONCLUSIONS: One
      case of hepatic dysfunction was recorded in 243 cases after at least 4 weeks of
      low-dose oral dantrolene administration. Low-dose dantrolene can be used safely
      with meticulous clinical and laboratory monitoring.

PMID- 21878206
TI  - Tongue-based biofeedback for balance in stroke: results of an 8-week pilot study.
AB  - OBJECTIVE: To assess balance recovery and quality of life after tongue-placed
      electrotactile biofeedback training in patients with stroke. DESIGN: Prospective
      multicenter research design. SETTING: Outpatient rehabilitation clinics.
      PARTICIPANTS: Patients (N=29) with chronic stroke. INTERVENTIONS: Patients were
      administered 1 week of therapy plus 7 weeks of home exercise using a novel tongue
      based biofeedback balance device. MAIN OUTCOME MEASURES: The Berg Balance Scale
      (BBS), Timed Up and Go (TUG), Activities-Specific Balance Confidence (ABC) Scale,
      Dynamic Gait Index (DGI), and Stroke Impact Scale (SIS) were performed before and
      after the intervention on all subjects. RESULTS: There were statistically and
      clinically significant improvements from baseline to posttest in results for the
      BBS, DGI, TUG, ABC Scale, and some SIS domains (Mobility, Activities of Daily
      Living/Instrumental Activities of Daily Living, Social, Physical, Recovery
      domains). Average BBS score increased from 35.9 to 41.6 (P<.001), and DGI score,
      from 11.1 to 13.7 (P<.001). Time to complete the TUG decreased from 24.7 to 20.7
      seconds (P=.002). Including the BBS, DGI, TUG, and ABC Scale, 27 subjects
      improved beyond the minimal detectable change with 95% certainty (MDC-95) or
      minimal clinically important difference (MCID) in at least 1 outcome and 3
      subjects improved beyond the MDC-95 or MCID in all outcomes. CONCLUSIONS:
      Electrotactile biofeedback seems to be a promising integrative method to balance
      training. A future randomized controlled study is needed.

PMID- 21878208
TI  - Differential improvements in lipid profiles and Framingham recurrent risk score
      in patients with and without diabetes mellitus undergoing long-term cardiac
      rehabilitation.
AB  - OBJECTIVE: To determine whether lipid profiles and recurrent coronary heart
      disease (CHD) risk could be modified in patients with and without diabetes
      mellitus undergoing long-term cardiac rehabilitation (CR). DESIGN: Retrospective
      analysis of patient case records. SETTING: Community-based phase 4 CR program.
      PARTICIPANTS: Patients without diabetes (n=154; 89% men; mean +/- SD age, 59.6 +/
      8.5y; body mass index [BMI], 27.0 +/- 3.5 kg/m2) and patients with diabetes
      (n=20; 81% men; mean age, 63.0 +/- 8.7y; BMI, 28.7 +/- 3.3 kg/m2) who completed
      15 months of CR. INTERVENTIONS: Exercise testing and training, risk profiling,
      and risk-factor education. MAIN OUTCOME MEASURES: Cardiometabolic risk factors
      and 2- to 4-year Framingham recurrent CHD risk scores were assessed. RESULTS: At
      follow up, a significant main effect for time was evident for decreased body mass
      and waist circumference and improved low-density lipoprotein cholesterol (LDL-C)
      level and submaximal cardiorespiratory fitness (all P<.05), showing the benefits
      of CR in both groups. However, a significant group-by-time interaction effect was
      evident for high-density lipoprotein cholesterol (HDL-C) level and total
      cholesterol (TC)/HDL-C ratio (both P<.05). TC/HDL-C ratio improved (5.0 +/- 1.5
      to 4.4 +/- 1.3) in patients without diabetes, but showed no improvement in
      patients with diabetes (4.8 +/- 1.6 v 4.9 +/- 1.6). CONCLUSIONS: We showed that
      numerous anthropometric, submaximal fitness, and cardiometabolic risk variables
      (especially LDL-C level) improved significantly after long-term CR. However, some
      aspects of cardiometabolic risk (measures incorporating TC and HDL-C) improved
      significantly in only the nondiabetic group.

PMID- 21878207
TI  - Combined aerobic and resistance exercise program improves task performance in
      patients with heart failure.
AB  - OBJECTIVES: To assess the effects of a home-based aerobic and resistance training
      program on the physical function of adults with New York Heart Association (NYHA)
      class II and III patients and systolic heart failure (HF). DESIGN: Randomized
      controlled trial. SETTING: Home based. PARTICIPANTS: Stable patients (N=24; mean
      age, 60 +/- 10 y; left ventricular ejection fraction, 25% +/- 9%; 50% white; 50%
      women) with New York Heart Association (NYHA) classes II and III (NYHA class III,
      58%) systolic heart failure (HF). INTERVENTION: A 12-week progressive home-based
      program of moderate-intensity aerobic and resistance exercise. Attention control
      wait list participants performed light stretching and flexibility exercises. MAIN
      OUTCOME MEASURES: A 10-item performance-based physical function measure, the
      Continuous Scale Physical Functional Performance test (CS-PFP10), was the major
      outcome variable and included specific physical activities measured in time to
      complete a task, weight carried during a task, and distance walked. Other
      measures included muscle strength, HRQOL (Minnesota Living With Heart Failure
      Questionnaire, Epworth Sleepiness Scale), functional capacity (Duke Activity
      Status Index), and disease severity (brain natriuretic peptide) levels. RESULTS:
      After the exercise intervention, 9 of 10 specific task activities were performed
      more rapidly, with increased weight carried by exercise participants compared
      with the attention control wait list group. Exercise participants also showed
      significant improvements in CS-PFP10 total score (P<.025), upper and lower muscle
      strength, and HRQOL (P<.001) compared with the attention control wait list group.
      Adherence rates were 83% and 99% for the aerobic and resistance training,
      respectively. CONCLUSIONS: Patients with stable HF who participate in a moderate
      intensity combined aerobic and resistance exercise program may improve
      performance of routine physical activities of daily living by using a home-based
      exercise approach. Performance-based measures such as the CS-PFP10 may provide
      additional insights into physical function in patients with HF that more commonly
      used exercise tests may not identify. Early detection of subtle changes that may
      signal declining physical function that are amenable to intervention potentially
      may slow further loss of function in this patient population.

PMID- 21878209
TI  - Repeated six-minute walk tests for outcome measurement and exercise prescription
      in outpatient cardiac rehabilitation: a longitudinal study.
AB  - OBJECTIVE: To determine whether repeated 6-minute walk tests (6MWTs) are required
      for outcome measurement and exercise prescription in a typical cardiac
      rehabilitation (CR) population. DESIGN: Prospective longitudinal observational
      study. SETTING: Outpatient community health center. PARTICIPANTS: Sixty-one of
      154 consecutive patients. INTERVENTION: 6MWTs (N = 2) were conducted at 3
      assessment points: at CR start, postcompletion, and 6-months postcompletion. MAIN
      OUTCOME MEASURE: 6MWT distance (6MWD). RESULTS: Mean 6MWD for the first (6MWT1)
      and second (6MWT2) 6MWTs at the 3 assessment points were 507 +/- 85 (522 +/- 84),
      532 +/- 86 (560 +/- 87), and 549 +/- 99 (575 +/- 107)m. Repeated 6MWDs strongly
      correlated at each assessment point, with intraclass correlation coefficients of
      .96 (95% confidence interval [CI], 0.93-.98), .97 (95% CI, .92-.98), and .94 (95%
      CI, .89-.97), respectively. Relative increases in mean 6MWD from 6MWT1 to 6MWT2
      at each assessment point were 3%, 5%, and 5%, respectively (P<.001 in each case).
      Differences in walking speed derived from 6MWD1 and 6MWD2 did not translate into
      differences in exercise prescription. CONCLUSIONS: The difference between 6MWD1
      and 6MWD2 was consistent regardless of previous exposure to 6MWTs. A single 6MWT
      was as effective as 2 repeated 6MWTs for outcome measurement and exercise
      prescription. We therefore recommend that when 6MWDs are used for CR outcome
      measurement, either a single 6MWT be used or the number of 6MWTs performed be
      consistent at all assessment points.

PMID- 21878210
TI  - Factors associated with older patients' engagement in exercise after hospital
      discharge.
AB  - OBJECTIVES: To identify factors that are associated with older patients'
      engagement in exercise in the 6 months after hospital discharge. DESIGN: A
      prospective observational study using qualitative and quantitative evaluation.
      SETTING: Follow-up of hospital patients in their home setting after discharge
      from a metropolitan general hospital. PARTICIPANTS: Participants (N=343) were
      older patients (mean age +/- SD, 79.4 +/- 8.5y) discharged from medical,
      surgical, and rehabilitation wards and followed up for 6 months after discharge.
      INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Self-perceived awareness
      and risk of falls measured at discharge with a survey that addressed elements of
      the Health Belief Model. Engagement and self-reported barriers to engagement in
      exercise measured at 6 months after discharge using a telephone survey. RESULTS:
      Six months after discharge, 305 participants remained in the study, of whom 109
      (35.7%) were engaging in a structured exercise program. Multivariable logistic
      regression analysis demonstrated participants were more likely to be engaging in
      exercise if they perceived they were at risk of serious injury from a fall (odds
      ratio [OR] =.61; 95% confidence interval [CI], .48-.78; P<.001), if exercise was
      recommended by the hospital physiotherapist (OR=1.93; 95% CI, 1.03-3.59; P=.04),
      and if they lived with a partner (OR=1.97; 95% CI, 1.18-3.28; P=.009). Barriers
      to exercise identified by 168 participants (55%) included low self-efficacy, low
      motivation, medical problems such as pain, and impediments to program delivery.
      CONCLUSIONS: Older patients have low levels of engagement in exercise after
      hospital discharge. Researchers should design exercise programs that address
      identified barriers and facilitators, and provide education to enhance motivation
      and self-efficacy to exercise in this population.

PMID- 21878211
TI  - Satisfaction with activity and participation and its relationships with body
      functions, activities, or environmental factors in stroke patients.
AB  - OBJECTIVES: To report the body functions, activities, and participation of stroke
      patients, and to investigate the relationships over time with the patients'
      perceived satisfaction with their level of activity and participation. DESIGN:
      Descriptive. SETTING: Hospital, home. PARTICIPANTS: Stroke patients (N = 45; mean
      age +/- SD, 69 +/- 10.7y) assessed by the same examiner. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: The Stroke Impairment Assessment Set was used
      to measure body functions, the Mini-Mental State Examination was used to measure
      cognitive level, and the Depression subscale of the Hospital Anxiety and
      Depression Scale was used to measure mood level. The ABILHAND and ABILOCO scales
      were used to measure activity, and the SATIS-Stroke questionnaire was used to
      measure satisfaction with activities and participation. Social and physical
      environmental factors were assessed by the World Health Organization
      International Classification of Functioning, Disability and Health Checklist
      Version 2.1a Clinician form. checklist. Patients were assessed during the acute
      (1 wk), postacute (3 mo), and chronic (6 mo) phases after stroke onset. RESULTS:
      Significant changes were observed over time in stroke body functions, cognitive
      status, manual and locomotion abilities, and satisfaction with activity and
      participation. At 1 week, satisfaction with activity and participation was not
      related to any body functions, activities, or environmental factors. At 3 months,
      manual ability was the only variable that was significantly related to
      satisfaction. During the chronic phase, manual ability and body functions were
      the best predictors of the stroke patient's perceived satisfaction. However, this
      combination of factors predicted only 43% of the variation in the SATIS-Stroke
      measures. CONCLUSIONS: Satisfaction with activity and participation cannot simply
      be inferred from body functions and activities, because it depends on complex
      interactions between functional, personal, and environmental factors.

PMID- 21878212
TI  - Arm motor control as predictor for hypertonia after stroke: a prospective cohort
      study.
AB  - OBJECTIVES: To analyze the development of hypertonia in the hemiparetic elbow
      flexors, and to explore the predictive value of arm motor control on hypertonia
      in a cohort of first-ever stroke survivors in the first 6 months poststroke.
      DESIGN: A prospective cohort study. SETTING: A cohort of stroke survivors from a
      large, university-affilliated hospital in The Netherlands. PARTICIPANTS: Patients
      (N=50) with first-time ischemic strokes and initial arm paralysis who were
      admitted to a stroke unit. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      At 48 hours, 10 to 12 days, 3 and 6 months poststroke, hypertonia and arm motor
      control were assessed using the Modified Ashworth Scale and the Fugl-Meyer
      Assessment arm score. RESULTS: The incidence rate of hypertonia reached its
      maximum before the third month poststroke (30%). Prevalence was 42% at 3 and 6
      months. Participants with poor arm motor control at 48 hours poststroke were 13
      times more likely to develop hypertonia in the first 6 months poststroke than
      those with moderate to good arm motor control. These results were not confounded
      by the amount of arm function training received. CONCLUSIONS: Hypertonia develops
      in a large proportion of patients with stroke, predominantly within the first 3
      months poststroke. Poor arm motor control is a risk factor for the development of
      hypertonia.

PMID- 21878214
TI  - Assessment of arm activity using triaxial accelerometry in patients with a
      stroke.
AB  - OBJECTIVE: To study the validity of accelerometry in the assessment of arm
      activity of patients with impaired arm function after stroke. DESIGN: Cross
      sectional concurrent validity study. SETTING: Rehabilitation center.
      PARTICIPANTS: Patients (N=45) at different stages after stroke. INTERVENTIONS:
      Not applicable. MAIN OUTCOME MEASURES: All patients wore 2 triaxial
      accelerometers around their wrists during 3 consecutive days. Arm activity was
      assessed, based on unilateral (activity of the affected arm) and bilateral
      accelerometry (ratio between the activity of the affected and nonaffected arm).
      The Motor Activity Log-26 (MAL-26) Amount of Use (AOU) scale was used as the main
      external criterion to test the concurrent validity of arm accelerometry. In
      addition, the MAL-26 Quality of Movement (QOM) scale and the Stroke Impact Scale
      (SIS) subscale Hand Function were used. To test the divergent validity, the SIS
      subscale Mobility was used. Spearman correlation coefficients were calculated. In
      an additional regression analysis, the hypothesized confounding influence of
      spasm, therapy intensity, and interobserver differences was studied. RESULTS:
      Both unilateral (rho=.58, P<.001) and bilateral (rho=.60, P<.001) accelerometry
      were significantly related to the MAL-AOU scale. Associations of both unilateral
      and bilateral accelerometry with the MAL-QOM and SIS subscale Hand Function
      corroborated these findings. The SIS subscale Mobility was not significantly
      associated with unilateral accelerometry (rho=.41, P=.01) or bilateral
      accelerometry (rho=.23, P=.11). None of the hypothesized confounders influenced
      these associations significantly. CONCLUSIONS: Based on the results, both the
      concurrent and divergent validity of unilateral and bilateral arm accelerometry
      for measuring arm activity after stroke are good.

PMID- 21878213
TI  - Five times sit-to-stand test performance in Parkinson's disease.
AB  - OBJECTIVES: To (1) determine intrarater and test-retest reliability of the Five
      times sit-to-stand test (FTSTS) in Parkinson's disease (PD), (2) characterize
      FTSTS performance in PD at different disease stages, (3) determine predictors of
      FTSTS performance in PD, and (4) determine the utility of the FTSTS for
      discriminating between fallers and nonfallers with PD, identifying an appropriate
      cutoff score to delineate between these groups. DESIGN: Measurement study of
      community-dwelling individuals with idiopathic PD. SETTING: A medical school
      laboratory. PARTICIPANTS: Participants (N=82) were recruited via population-based
      sampling. The final sample included 80 participants. Two were excluded because of
      exclusion criteria and an unrelated illness, respectively. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: FTSTS time (seconds) was the primary outcome
      measure. Secondary outcome measures included the Mini-Balance Evaluation Systems
      Test (Mini-BEST), Maximal Voluntary Isometric Contraction-Quadriceps, 9-Hole Peg
      Test (9HPT), 6-minute walk, Freezing of Gait Questionnaire, Activities-Specific
      Balance Confidence Scale, Physical Activity Scale for the Elderly, Parkinson's
      Disease Questionnaire-39, and Movement Disorders Society-Unified Parkinson's
      Disease Rating Scale. RESULTS: Interrater and test-retest reliability for the
      FTSTS were high (intraclass correlation coefficients: .99 and .76, respectively).
      Mean FTSTS performance was 20.25 +/- 14.12 seconds. All mobility measures were
      significantly correlated with FTSTS (P<.01). The Mini-BEST and 9HPT together
      explained 53% of the variance in FTSTS. Receiver operating characteristic
      analysis determined a cutoff of 16.0 seconds (sensitivity, .75; specificity, .68)
      for discriminating between fallers and nonfallers, with an area under the curve
      of .77. CONCLUSIONS: The FTSTS is a quick, easily administered measure that is
      useful for gross determination of fall risk in individuals with PD.

PMID- 21878215
TI  - Instrument validity and reliability of a choice response time test for subjects
      with incomplete spinal cord injury: relationship with function.
AB  - OBJECTIVES: To investigate instrument validity and reliability of a choice
      response time (CRT) test for the lower extremities in subjects with incomplete
      spinal cord injury (iSCI). CRT in subjects with iSCI is hypothesized to be
      increased because of, for example, muscle weakness or increased corticospinal
      conduction velocity. DESIGN: Case-control study. SETTING: Spinal cord injury
      center of a university hospital in Switzerland. PARTICIPANTS: Patients with iSCI
      (N=28; mean age, 51y; 57% men; neurologic level, C3-L5; median time since injury,
      148d) compared with age-matched controls (50% men) to assess instrument validity
      by comparing CRTs. A subgroup of subjects with iSCI (n = 9) and controls (n = 13)
      to determine reliability. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES:
      CRTs of the lower extremity were assessed and divided into reaction and movement
      times. Additionally, subjects with iSCI were tested for lower-extremity muscle
      strength, gait capacity and mobility, independence, history of falls, and fear of
      falling. RESULTS: CRTs in the control group (mean +/- SD, 517 +/- 71 ms) were
      significantly faster than those in the iSCI group (743 +/- 177 ms; P<.001).
      Retest reliability was high in controls (intraclass correlation coefficient
      [ICC]>.98) and subjects with iSCI (ICC>.93). In subjects with iSCI, there were
      moderate to good correlations between CRT and several functional outcome
      measures, but not with reported number of falls. CONCLUSION: Lower-extremity CRT
      testing appears reliable in healthy controls and ambulating subjects with iSCI.

PMID- 21878216
TI  - Autonomic dysreflexia during urodynamic examinations in patients with suprasacral
      spinal cord injury.
AB  - OBJECTIVE: To investigate blood pressure (BP) and pulse rate (PR) changes during
      urodynamic (UD) examinations in patients with suprasacral spinal cord injury
      (SCI). DESIGN: A case control study. SETTING: Tertiary hospital affiliated with a
      medical university. PATIENTS: Control subjects (n=22) and patients with
      suprasacral SCI (n=120). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES:
      Systolic (SBP) and diastolic BP (DBP) and PR before and during UD studies.
      RESULT: Healthy subjects had an average SBP change of 9.7 +/- 10.6 mm Hg and a
      maximal SBP increase of 21 mm Hg. Autonomic dysreflexia (AD) was defined as an
      SBP increase of 20mm Hg or more, and incidence rates were 36.7% overall, 42.6% in
      patients with injury level at or above T6, and 15.4% in patients with lesions
      below T6. Both SBP and DBP changes in patients with SCI showed significant
      negative correlations with injury levels (r=-.383 and -.315; P<.05). The BP
      increase was more significant in patients with SCI who had detrusor sphincter
      dyssynergia (DSD), especially the continuous type, or severely impaired bladder
      compliance than in those who did not. Most patients (75%) had no significant PR
      changes (within 10 beats/min) during AD responses and only 22.7% had a decrease
      of 10 beats/min or more. Patients younger than 50 years had a greater PR decrease
      than those 50 years or older (-7.1 +/- 9.0 vs 0.7 +/- 11.4 beats/min; P<.05).
      CONCLUSIONS: AD occurred not only in patients with lesions above T6, but also in
      those with lower lesion levels. Patients with higher injury level, continuous
      DSD, or a poorly compliant bladder had greater SBP changes during UD studies.
      During AD reactions, younger patients tended to have a greater PR decrease than
      older patients.

PMID- 21878218
TI  - Burden of Chinese stroke family caregivers: the Hong Kong experience.
AB  - OBJECTIVE: To ascertain the clinical and sociodemographic factors associated with
      family caregivers' burden in Chinese patients with stroke in Hong Kong. DESIGN:
      Cross-sectional design. SETTING: Stroke Clinic. PARTICIPANTS: Patients (N=123)
      from a stroke clinic and their family caregivers. INTERVENTIONS: Not applicable.
      MAIN OUTCOME MEASURES: Predictive factors of family caregivers' burden in Chinese
      stroke patients in Hong Kong. Caregivers' burden was assessed with the Caregiving
      Burden Scale (CBS). Patients' and caregivers' sociodemographic data and clinical
      characteristics were recorded. Physical and psychological conditions were
      measured and rated with the following instruments: Cumulative Illness Rating
      Scale, Geriatric Depression Scale (GDS), Barthel Index, Instrumental Activities
      of Daily Living, Mini-Mental State Examination, Lubben Social Network Scale,
      Modified Life Event Scale (MLES), Hospital Anxiety and Depression Scale (HADS),
      and a single question about fatigue. RESULTS: In the univariate analysis, the CBS
      score had significant correlations with certain characteristics of caregivers
      (sex, GDS, HADS, depressive symptoms, fatigue, and MLES) and those of patients'
      (sex, age, education, GDS). Regression analysis revealed that caregivers' GDS and
      patients' education were the independent correlates of the CBS. CONCLUSIONS: The
      severity of depressive symptoms in Chinese stroke caregivers and patients'
      education are independent factors associated with the caregivers' burden. Further
      studies evaluating interventions on caregivers' burden should include the
      assessment and management of mood disorders.

PMID- 21878217
TI  - Factors influencing receipt of outpatient rehabilitation services among veterans
      following lower extremity amputation.
AB  - OBJECTIVE: To determine patient-, treatment-, and facility-level characteristics
      associated with receiving outpatient rehabilitation services after lower
      extremity amputation within the Veterans Affairs (VA) system. DESIGN:
      Observational study. SETTING: All Veterans Affairs Medical Centers (VAMCs).
      PARTICIPANTS: Veterans (N=4165) with lower extremity amputation discharged from
      VAMCs between October 1, 2002, and September 20, 2004. INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Receipt of outpatient rehabilitation services
      up to 1 year postdischarge. A Cox proportional hazards model was used to
      determine the adjusted hazard ratio and 95% confidence interval of veterans to
      receive outpatient services. RESULTS: Sixty-five percent of veterans with lower
      extremity amputation received outpatient services. Older veterans, patients
      admitted for surgical amputation from extended care rather than transferred from
      another hospital, and those with transfemoral and/or bilateral rather than
      unilateral transtibial amputations were less likely to receive outpatient
      services. Those with serious comorbidities and those who had procedures for acute
      central nervous system disorders, active cardiac pathology, serious nutritional
      compromise, and severe renal disease during the surgical hospitalization less
      often initiated outpatient care. Patients who received inpatient consultative
      rehabilitation compared with inpatient specialized rehabilitation, and who were
      treated in the Northeast compared with the Southeast less often initiated
      outpatient care. Finally, those discharged to home or other locations rather than
      extended care had an initial increased likelihood of receiving outpatient
      service, but by 180 days postdischarge those discharged to extended care were
      more likely to initiate outpatient services. CONCLUSIONS: Both clinical
      characteristics and types of rehabilitation services received appear to influence
      the receipt of outpatient rehabilitation services. Geographic location also
      affected the receipt of outpatient rehabilitation, suggesting that care patterns
      are not standardized across the nation.

PMID- 21878219
TI  - Determinants of intensity of participation in leisure and recreational activities
      by youth with cerebral palsy.
AB  - OBJECTIVE: To test a model of determinants of intensity of participation in
      leisure and recreational activities by youth with cerebral palsy (CP). DESIGN:
      Prospective cohort study. SETTING: Children's hospitals (N=7). PARTICIPANTS:
      Youth with CP (N=205; age, 13-21y) and their parents. The sample included 107
      (57.2%) males and 26 (12.7%) to 57 (27.8%) youth in each of the 5 levels of the
      Gross Motor Function Classification System (GMFCS). INTERVENTIONS: Not
      applicable. MAIN OUTCOME MEASURES: Youth completed the Children's Assessment of
      Participation and Enjoyment by means of an interview. Parents completed the
      Pediatric Outcomes Data Collection Instrument, Family Environment Scale, Coping
      Inventory, Measure of Processes of Care, a demographic questionnaire, and a
      services questionnaire. RESULTS: Structural equation modeling was used to test
      the model. Fit statistics indicate good model fit. The model explains 35% of the
      variance in intensity of participation. Path coefficients (P <= .05) indicate
      that higher physical ability, higher enjoyment, younger age, female sex, and
      higher family activity orientation are associated with higher intensity of
      participation. GMFCS level and caregiver education have indirect effects on
      intensity of participation. The path between services and intensity of
      participation was not significant. CONCLUSIONS: Participation by youth with CP is
      influenced by multiple factors. The influence of physical activity supports the
      importance of activity accommodations and assistive technology for youth who are
      not capable of improving physical ability. Knowledge of family activity
      orientation is important for identifying opportunities for participation. The
      unexplained variance suggests that the model should include other determinants,
      such as physical accessibility and availability of transportation and community
      leisure and recreational activities.

PMID- 21878220
TI  - Extra physical therapy reduces patient length of stay and improves functional
      outcomes and quality of life in people with acute or subacute conditions: a
      systematic review.
AB  - OBJECTIVES: To investigate whether extra physical therapy intervention reduces
      length of stay and improves patient outcomes in people with acute or subacute
      conditions. DATA SOURCES: Electronic databases CINAHL, MEDLINE, AMED, PEDro,
      PubMed, and EMBASE were searched from the earliest date possible through May
      2010. Additional trials were identified by scanning reference lists and citation
      tracking. STUDY SELECTION: Randomized controlled trials evaluating the effect of
      extra physical therapy on patient outcomes were included for review. Two
      reviewers independently applied the inclusion and exclusion criteria, and any
      disagreements were discussed until consensus could be reached. Searching
      identified 2826 potentially relevant articles, of which 16 randomized controlled
      trials with 1699 participants met inclusion criteria. DATA EXTRACTION: Data were
      extracted using a predefined data extraction form by 1 reviewer and checked for
      accuracy by another. Methodological quality of trials was assessed independently
      by 2 reviewers using the PEDro scale. DATA SYNTHESIS: Pooled analyses with random
      effects model to calculate standardized mean differences (SMDs) and 95%
      confidence intervals (CIs) were used in meta-analyses. When compared with
      standard physical therapy, extra physical therapy reduced length of stay (SMD=
      .22; 95% CI, -.39 to -.05) (mean difference of 1d [95% CI, 0-1] in acute settings
      and mean difference of 4d [95% CI, 0-7] in rehabilitation settings) and improved
      mobility (SMD=.37; 95% CI, .05-.69), activity (SMD=.22; 95% CI, .07-.37), and
      quality of life (SMD=.48; 95% CI, .29-.68). There were no significant changes in
      self-care (SMD=.35; 95% CI, -.06-.77). CONCLUSIONS: Extra physical therapy
      decreases length of stay and significantly improves mobility, activity, and
      quality of life. Future research could address the possible benefits of providing
      extra services from other allied health disciplines in addition to physical
      therapy.

PMID- 21878221
TI  - Physical fitness in people after burn injury: a systematic review.
AB  - OBJECTIVE: To gain insight into the physical fitness of people after burn injury
      compared with healthy subjects, and to present an overview of the effectiveness
      of exercise training programs in improving physical fitness in people after burn
      injury. DATA SOURCES: Electronic databases EMBASE, PubMed, and Web of Science
      were searched for relevant publications. Additionally, references from retrieved
      publications were checked. STUDY SELECTION: The review includes studies that
      provide quantitative data from objective measures of physical fitness of both the
      intervention group and the control group. DATA EXTRACTION: Characteristics of
      each study such as study design, institution, and intervention are reported, as
      well as mean ages and burn sizes of the subjects. Results are divided into 5
      components of physical fitness-muscular strength, muscular endurance, body
      composition, cardiorespiratory endurance, and flexibility-and reported for each
      component separately. DATA SYNTHESIS: Eleven studies met the inclusion criteria,
      and their methodological quality was assessed using the PEDro score and a
      modified Sackett scale. Six studies were used for the comparison of physical
      fitness in burned and nonburned subjects, and 9 studies for evaluating the
      effectiveness of exercise training programs. CONCLUSIONS: Physical fitness is
      affected in people with extensive burns, and exercise training programs can bring
      on relevant improvements in all components. However, because of the great
      similarities in the subjects and protocols used in the included studies, the
      current knowledge is incomplete. Future research should include people of all
      ages with a broad range of burn sizes, for both short-term and long-term
      outcomes.

PMID- 21878222
TI  - Peripheral nerve involvement in a neurofibromatosis type 2 patient with plexiform
      neurofibroma of the cauda equina: a sonographic vignette.
AB  - We report a 20-year-old man with cauda equina syndrome and neurofibromatosis type
      2. We discuss the role of sonographic and electromyographic evaluations in the
      management of our patient and suggest the use of sonographic imaging for
      visualization of peripheral nerve pathologic states, especially when involvement
      is widespread.

PMID- 21878223
TI  - Hyperbaric oxygen therapy for traumatic brain injury: still an enigma.
AB  - With their article on the use of HBOT for post TBI dysautonomia, Lv and
      colleagues discuss a novel use for this form of treatment. Although HBOT has been
      a part of our TBI treatment armamentarium for many years, its use remains a very
      controversial issue. In this commentary, the science and research studies behind
      HBOT for TBI are reviewed, hopefully leaving the reader with an adequate
      knowledge base to answer a patient or family's inquiries as to the usefulness of
      HBOT for TBI.

PMID- 21878224
TI  - Posterior tibial nerve: a misnomer.

PMID- 21878225
TI  - Endovascular balloon occlusion of the aorta is superior to resuscitative
      thoracotomy with aortic clamping in a porcine model of hemorrhagic shock.
AB  - BACKGROUND: Noncompressible torso hemorrhage is the leading cause of potentially
      preventable death on the modern battlefield. The objective of this study is to
      characterize resuscitative aortic balloon occlusion (BO) compared to thoracotomy
      with aortic clamping in a model of hemorrhagic shock. METHODS: A total of 18
      swine (3 groups; 6 animals/group) were used in this study. Swine in class IV
      shock underwent no aortic occlusion (NO), thoracotomy and clamp occlusion (CO),
      or endovascular BO. Animals in the NO group underwent direct placement of a
      temporary vascular shunt (TVS) at the injury site, whereas animals in the CO and
      BO groups underwent aortic occlusion before TVS placement. Hemodynamic and
      physiologic measures were collected. RESULTS: The central aortic pressure,
      carotid blood flow and brain oxygenation as measured by oximetry increased in the
      CO and BO groups compared to the NO group (P < .05). During resuscitation, the BO
      group was less acidotic than the CO group (pH,7.35 vs 7.24; P < .05) with a lower
      serum lactate level (4.27 vs 6.55; P < .05) and pCO2 level (43.5 vs 49.9; P <
      .05). During resuscitation, the BO group required less fluid (667 mL vs 2,166 mL;
      P < .05) and norepinephrine (0 mcg vs 52.1 mcg; P < .05) than the CO group.
      CONCLUSION: Resuscitative aortic BO increases central perfusion pressures with
      less physiologic disturbance than thoracotomy with aortic clamping in a model of
      hemorrhagic shock. Endovascular BO of the aorta should be explored further as an
      option in the management of noncompressible torso hemorrhage.

PMID- 21878226
TI  - Pattern recognition receptor gene expression in ischemia-induced flap
      revascularization.
AB  - BACKGROUND: The innate immune system is the major contributor to acute
      inflammation induced by microbial infection or tissue damage. Germline-encoded
      pattern recognition receptors (PRRs) are responsible for sensing the presence of
      micro-organisms and endogenous molecules released from damaged cells. We
      performed microarray analyses on ischemic wound tissue to investigate the
      temporal relationship between PRR gene expression, wound perfusion, and flap
      revascularization. METHODS: A cranial-based, peninsular-shaped myocutaneous flap
      was surgically created on the dorsum of C57BL6 mice (n = 25 total; n = 20 with
      flap). Laser speckle contrast imaging was utilized to study the pattern of flap
      ischemia and return of functional revascularization. Flap microvascular density
      was determined by image analysis of CD-31-immunostained sections. Total RNA was
      isolated from homogenized flap tissue and was converted to cDNA (RT), which was
      hybridized to a microarray of pathway-focused genes. Microarray results were
      validated with quantitative real-time reverse transcription-polymerase chain
      reaction (qRT-PCR). RESULTS: Laser speckle contrast imaging predicted the spatial
      and temporal pattern of ischemia and functional revascularization. Histologic
      analysis demonstrated early leukocyte infiltration and later engraftment,
      resulting in flap revascularization by new blood vessel growth from the recipient
      bed and dilatation of preexisting proximal flap vasculature. qRT-PCR demonstrated
      significant early gene expression of select PRRs, cytokines, chemokines, and
      growth factors, peaking by 48 hours, and returning toward baseline but remaining
      elevated at 10 days. CONCLUSION: Surgical and ischemic tissue injury resulted in
      the early gene expression of select PRRs, which may bind with endogenous
      molecules released from ischemic or necrotic cells, leading to transcription of
      genes involved in wound inflammation and angiogenesis.

PMID- 21878227
TI  - Histone deacetylase inhibitors enhance endothelial cell sprouting angiogenesis in
      vitro.
AB  - BACKGROUND: Treatment with histone deacetylases inhibitors (HDACi) such as
      valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA) has been shown to
      improve survival after lethal insults through mechanisms that are incompletely
      understood. Cell survival under adverse conditions requires a healthy network of
      capillaries to ensure adequate oxygen delivery. Angiogenic activation of
      endothelial cells to migrate and form sprouts is associated with characteristic
      changes in gene expression profiles. Because HDACi can modulate expression of
      various genes involved in angiogenic activity, we investigated the effect of
      these agents on capillary-like sprout formation in this study. METHODS: Human
      umbilical vein endothelial cells (HUVECs) were cultured as multicellular
      spheroids within a type I collagen matrix, which promotes formation of sprouts
      resembling angiogenesis in vitro. HUVECs were cultured as multicellular spheroids
      within a type I collagen matrix, which promotes formation of sprouts (in vitro
      angiogenesis). Cells were cultured under the following conditions: Control (no
      growth factors); VPA (1 mmol/L); vascular endothelial growth factor (VEGF; 10
      ng/mL); VPA + VEGF; SAHA (5 mmol/L), and SAHA + VEGF. After 24 hours of
      treatment, the length of spheroid sprouting and cell migration was assessed
      quantitatively. The levels of acetylated histone H3, phosphor-extracellular
      signal-regulated kinase (ERK)1/2, and beta-catenin in HUVECs were measured by
      Western blotting at 6 hours after treatment. RESULTS: High levels of acetylated
      histone H3 were detected in VPA and SAHA treated-groups. Compared with the VEGF
      alone treated group (2379 +/- 147.1 MUm), the spheroid sprouting was 1.7 times
      increased with VPA and VEGF combined treatment (3996 +/- 192.5 MUm; P < .01).
      Cell migrations did not show a significant difference after addition of VPA,
      whereas SAHA suppressed migration. Expression of beta-catenin was significantly
      increased by VPA and SAHA treatments. Addition of VPA greatly enhanced expression
      of phosphor-ERK1/2. CONCLUSION: Exposure of HUVECs to VPA and SAHA increased the
      expression of beta-catenin and enhanced spheroid sprout formation in vitro.
      Modulation of HDAC-dependent pathways may offer a novel approach to alter
      angiogenic processes and provide a useful therapeutic target.

PMID- 21878228
TI  - Surgeon-performed ultrasound can predict benignity in thyroid nodules.
AB  - BACKGROUND: Surgeon-performed ultrasound (SUS) has become an extension of the
      physical examination in the evaluation of patients with thyroid nodules. Amid
      concerns that too many "diagnostic" thyroidectomies are performed, this study
      examines the usefulness of SUS in predicting benign thyroid nodules. METHODS: A
      retrospective review of 624 patients with solitary or dominant thyroid nodules
      and prospectively collected data of SUS nodule features before thyroidectomy
      (benign = 407; malignant = 217) was performed. A specific model for statistical
      analysis was created to predict benignity. RESULTS: Significant predictors of
      benignity by SUS after logistic regression included isoechogenicity, cystic
      component, no microcalcifications, regular borders, and size <1 cm. The resultant
      specificity of this reduced model was 97.6% with a 10.6% sensitivity for
      predicting benign pathology. After excluding patients with lesions >4 cm or a
      history of thyroid cancer, thyroid nodules measuring 1-4 cm with the presence of
      the 4 other criteria by SUS was 98.5% specific for the detection of benign
      pathology (1.5% false-negative rate). CONCLUSION: Approximately 10% of
      thyroidectomy patients had benign nodules that were 1-4 cm, isoechoic, with
      regular borders, had a cystic component, and no microcalcifications by SUS.
      Patients without clinical risk factors and these SUS features may safely forego
      further fine needle aspiration and thyroid lobectomy, and can be monitored with
      serial ultrasound examinations.

PMID- 21878229
TI  - Identification of citrullinated histone H3 as a potential serum protein biomarker
      in a lethal model of lipopolysaccharide-induced shock.
AB  - BACKGROUND: Circulating proteins may serve as biomarkers for the early diagnosis
      and treatment of shock. We have recently demonstrated that treatment with
      suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor,
      significantly improves survival in a rodent model of lipopolysaccharide (LPS)
      induced septic shock. Preliminary proteomic data showed that LPS-induced shock
      altered a number of proteins in circulation, including histone H3 (H3) and
      citrullinated histone H3 (Cit H3). The present study was designed to confirm
      these findings and to test whether the pro-survival phenotype could be detected
      by an early alteration in serum biomarkers. METHODS: Three experiments were
      performed. In experiment I, Western blotting was performed on serum samples from
      male C57B1/6J mice (n = 9, 3/group) that belonged to the following groups: (a)
      LPS (20 mg/kg)-induced septic shock, (b) SAHA-treated septic shock, and (c) sham
      (no LPS, no SAHA). In experiment II, HL-60 granulocytes were cultured and treated
      with LPS (100 ng/m1) in the absence or presence of SAHA (10 MUmol/L). Sham (no
      LPS, no SAHA) granulocytes served as controls. The medium and cells were
      harvested at 3 hours, and proteins were measured with Western blots. In
      experiment III, a large dose (LD, 35 mg/kg) or small dose (SD, 10 mg/kg) of LPS
      was injected intraperitoneally into the C57B1/6J mice (n = 10 per group). Blood
      was collected at 3 hours, and serum proteins were determined by Western blots or
      enzyme-linked immunosorbent assay (ELISA). All of the Western blots were
      performed with antibodies against H3, Cit H3, and acetylated H3 (Ac H3). ELISA
      was performed with antibody against tumor necrosis factor (TNF)-alpha. Survival
      rates were recorded over 7 days. RESULTS: In experiment I, intraperitoneal (IP)
      injection of LPS (20 mg/kg) significantly increased serum levels of H3, which was
      prevented by SAHA treatment. In experiment II, LPS (100 ng/mL) induced expression
      and secretion of Cit H3 and H3 proteins in neutrophilic HL-60 cells, which was
      decreased by SAHA treatment. In experiment III, administration of LPS (LD) caused
      a rise in serum H3 and Cit H3 but not Ac H3 at 3 hours, and all of these animals
      died within 23 hours (100% mortality). Decreasing the dose of LPS (SD)
      significantly reduced the mortality rate (10% mortality) as well as the
      circulating levels of Cit H3 (non detectable) and H3. An increase in serum TNF
      alpha was found in both LPS (LD) and (SD) groups, but in a non-dose-dependent
      fashion. CONCLUSION: Our results reveal for the first time that Cit H3 is
      released into circulation during the early stages of LPS-induced shock. Moreover,
      serum levels of Cit H3 are significantly associated with severity of LPS-induced
      shock. Therefore, Cit H3 could serve as a potential protein biomarker for early
      diagnosis of septic shock, and for predicting its lethality.

PMID- 21878230
TI  - Posterior retroperitoneoscopic adrenalectomy is a safe and effective alternative
      to transabdominal laparoscopic adrenalectomy for pheochromocytoma.
AB  - INTRODUCTION: Laparoscopic adrenalectomy (LA) is a safe minimally invasive
      approach for treatment of pheochromocytoma (PHEO). Posterior retroperitoneoscopic
      adrenalectomy (PRA) is an alternative minimally invasive technique; however,
      there is a lack of data regarding the appropriateness of this approach in
      patients with PHEO. METHODS: Our endocrine surgery database was queried to
      identify patients who underwent LA or PRA for PHEO. Patient and tumor
      characteristics, as well as operative details and postoperative course were
      compared between the 2 groups. RESULTS: LA or PRA was attempted in 46 patients
      with PHEO (23 LA, 23 PRA). There were no differences in age, BMI, or tumor size
      between these groups. PRA was associated with significantly reduced operative
      times (99 min vs 145 min, P < .001), estimated blood loss (8.4 cc vs 123.8 cc, P
      = .02), and postoperative length of stay (1.9 nights vs 3.1 nights, P < .01).
      There was no significant difference in rates of conversion to an open procedure
      or perioperative complications between these groups. CONCLUSION: LA and PRA are
      both safe and effective approaches in patients with PHEO. In our experience, PRA
      results in decreased operative times, blood loss, and postoperative length of
      stay compared with LA. PRA has become our preferred approach for patients with
      PHEO.

PMID- 21878231
TI  - Chemokine receptor CXCR4 level in primary tumors independently predicts outcome
      for patients with locally advanced breast cancer.
AB  - BACKGROUND: Chemokine receptor CXCR4 is a marker of metastatic disease. We found
      initially that CXCR4 level is a predictive marker for patients with locally
      advanced breast cancer (LABC). We now confirm our initial observations. METHODS:
      We evaluated 77 LABC patients who had neoadjuvant therapy. Specimens were taken
      at the time of definitive operation. CXCR4 levels were detected with Western
      blots. CXCR4 expression >6.6-fold over known concentration of HeLa cells was
      defined as high. Primary endpoints were cancer recurrence and death. Statistical
      analyses were Kaplan-Meier curves, log-rank test, and Cox proportional hazard
      model. RESULTS: Median follow-up time was 42 months; 55 patients (71%) had low
      CXCR4 level. The 5-year overall survival for the low and high CXCR4 group was 78%
      and 50%, respectively (P = .015). The 5-year disease-free survival (DFS) for the
      low and high CXCR4 group was 67% and 41%, respectively (P = .024). On
      multivariate analysis, CXCR4 overexpression (P = .003) and nodal status (P =
      .044) were independent predictors of overall survival; CXCR4 overexpression (P =
      .003) and nodal status (P = .026) were also independent predictors of DFS.
      CONCLUSION: We confirmed that high CXCR4 levels in cancer specimens after
      neoadjuvant therapy independently predict a poor outcome for patients with LABC.

PMID- 21878232
TI  - Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II
      trials.
AB  - BACKGROUND: Neoadjuvant treatment has proven beneficial for many gastrointestinal
      (GI) malignancies, but no phase III trials have been completed examining this
      approach in pancreatic cancer. This meta-analysis examines the best available
      phase II trials using neoadjuvant treatment for resectable and
      borderline/unresectable pancreatic adenocarcinoma. METHODS: Phase II trials were
      identified using a MEDLINE search, and the Cochrane Central Register of
      Controlled Trials from 1960 to July 2010. Patients were divided into 2 groups:
      Patients with initially resectable tumors (group A), and patients with
      borderline/unresectable tumors (group B). Primary outcome measures were rate of
      resection and survival. Pooled proportions and 95% confidence intervals (CIs)
      were calculated using random-effects or fixed-effects models based on the
      heterogeneity of included studies. RESULTS: A total of 14 phase II clinical
      trials including 536 patients were analyzed. After treatment, resectability was
      65.8% (95% CI, 55.4-75.6%) compared with 31.6% in group B (95% CI, 14.0-52.5%). A
      partial response was observed in patients with borderline/unresectable tumors;
      31.8 (95% CI, 24.2-39.8%) in group B and 9.5% (95% CI, 2.9-19.4%) in group A (P =
      .003). Progressive disease was seen in 17.0% (95% CI, 11.9-22.7) of patients in
      group A versus 21.8% (95% CI, 10.1-36.5%) in group B (P = .006). Median survival
      in resected patients was 23 months for group A and 22 months for group B.
      CONCLUSION: Neoadjuvant treatment seems to have some activity in patients with
      borderline/unresectable pancreatic adenocarcinoma. Nearly one third of tumors
      initially deemed marginal for operative intervention were able to be ultimately
      resected after treatment. Until more effective targeted chemotherapeutics are
      developed, the only group of patients with pancreatic cancer that may benefit
      from neoadjuvant treatment are those with locally advanced disease.

PMID- 21878233
TI  - Irreversible electroporation is a surgical ablation technique that enhances gene
      transfer.
AB  - BACKGROUND: Reversible electroporation has long been used to transfer
      macromolecules into target cells in the laboratory by using an electric field to
      induce transient membrane permeability. Recently, the electric field has been
      modulated to produce permanent membrane permeability and cell death. This novel
      technique, irreversible electroporation (IRE), is being developed for nonthermal
      cancer ablation. We hypothesize that outside the central zone of IRE exists a
      peripheral zone of reversible electroporation where gene transfer may occur.
      METHODS: IRE of the liver was performed in a Yorkshire pig model with
      administration of a plasmid expressing the marker gene green fluorescent protein
      (GFP) by bolus or primed infusion through the hepatic artery or portal vein.
      After 6 hours, livers were harvested for fluorescent microscopy and histologic
      examination. RESULTS: Of 36 liver specimens treated with IRE and the GFP plasmid,
      31 demonstrated strong green fluorescence. Liver ablation by IRE was demarcated
      clearly on histology. CONCLUSION: IRE is a promising technique not only for
      operative tissue ablation but also for gene therapy. Because IRE ablation may
      leave behind intact tumor antigens, these findings encourage clinical studies of
      tumor ablation with delivery of immunostimulatory plasmids for combined local
      eradication and systemic immunotherapy.

PMID- 21878234
TI  - Bile salt supplementation acts via the farnesoid X receptor to alleviate
      lipopolysaccharide-induced intestinal injury.
AB  - BACKGROUND: Intestinal barrier integrity may be disrupted in many conditions
      allowing for bacterial invasion and ensuing systemic illness. We investigated the
      efficacy and mechanism of bile salts in protecting the intestinal mucosa
      integrity after injury through stimulation of cell proliferation and an increased
      resistance to apoptosis. METHODS: Over 7 days, wild-type C57Bl/6J and
      Nr1h4(tm1Gonz)/J (farnesoid X receptor [FXR] knockout) male mice received either
      liquid rodent chow alone (for control animals) or with added 50 mg/kg per day of
      taurodeoxycholic acid (TDCA; for experimental animals). On day 6, all mice
      received 10 mL/kg of lipopolysaccharide intraperitoneally. On day 7, small
      intestines were harvested. After immunohistochemistry with hematoxylin and eosin,
      activated caspase-3, and 5-bromo2'-deoxy-uridine (BrdU), mean proliferating and
      apoptotic cells were determined with light microscopy. In vitro, FXR proteins
      were immunoblotted from cultured cells after exposure to TDCA. FXR expression was
      then inhibited in the presence and absence of TDCA. Intestinal epithelial
      proliferation along with c-Myc and FXR protein expressions were determined.
      RESULTS: C57Bl/6J mice exhibited significant mucosal enterocyte proliferation and
      decreased mucosal enterocyte apoptosis when provided with supplemental TDCA in
      their diet. Inhibition of FXR, both in vivo and in vitro, prevented the bile salt
      induced enterocyte proliferation and resistance to apoptosis. TDCA exposure
      stimulated nuclear translocation of FXR resulting in increased expression of c
      Myc. CONCLUSION: A diet supplemented with bile salts, especially in patients who
      have decreased luminal bile salt, may prove beneficial and therapeutic in
      critical illness where intestinal injury is part of the spectrum.

PMID- 21878235
TI  - High-fat diet alters prostanoid balance and perfusion in ischemic myocardium of
      naproxen-treated swine.
AB  - BACKGROUND: The effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the
      cardiovascular system remains controversial, especially in patients with
      cardiovascular comorbidities. We used a swine model of chronic myocardial
      ischemia to investigate whether hypercholesterolemia alters the cardiovascular
      effects of the nonselective NSAID naproxen. METHODS: Yorkshire swine were fed
      normal chow (NAP; n = 7) or a high-fat diet (HF-NAP; n = 8). Chronic myocardial
      ischemia was created in all animals by left circumflex ameroid constrictor
      placement. All swine were started on oral naproxen (440 mg/day) at the time of
      ameroid placement. After 7 weeks, myocardial perfusion and microvessel reactivity
      in the ischemic territory were assessed. Tissue levels of prostanoid metabolites
      11-dehydrothromboxane B2 (11-d-TXB2) and 6-keto-prostaglandin F1-alpha (6-k
      PGF(1alpha)) were measured. Tissue was analyzed for capillary density and protein
      expression. RESULTS: Myocardial perfusion was significantly decreased in the HF
      NAP group both at rest and during ventricular pacing. Microvessel relaxation
      responses to sodium nitroprusside and adenosine 5'-diphosphate were similar
      between groups. Tissue 11-d-TXB2 levels were similar between groups, but tissue 6
      k-PGF(1alpha) was significantly decreased in the HF-NAP group (P = .001).
      Expression of thromboxane synthase was significantly higher in the HF-NAP group
      (P = .02), while prostacyclin synthase expression was significantly decreased in
      the HF-NAP group (P = .04). Capillary density was higher in the HF-NAP group (P =
      .005). Proangiogenic vascular endothelial growth factor (VEGF; P = .0002) and Akt
      (P = .01) were downregulated in the HF-NAP group. CONCLUSION: A high-fat diet
      impairs tissue perfusion in ischemic myocardium of naproxen-treated swine by
      shifting the prostanoid balance to favor production of thromboxane over
      prostacyclin. Dietary modification may improve myocardial blood flow and alter
      the safety profile in chronically ischemic cardiac patients taking naproxen.

PMID- 21878236
TI  - Continuous local delivery of interferon-beta stabilizes tumor vasculature in an
      orthotopic glioblastoma xenograft resection model.
AB  - BACKGROUND: High-grade glioblastomas have immature, leaky tumor blood vessels
      that impede the efficacy of adjuvant therapy. We assessed the ability of human
      interferon (hIFN)-beta delivered locally via gene transfer to effect vascular
      stabilization in an orthotopic model of glioblastoma xenograft resection.
      METHODS: Xenografts were established by injecting 3 grade IV glioblastoma cell
      lines (GBM6-luc, MT330-luc, and SJG2-luc) into the cerebral cortex of nude rats.
      Tumors underwent subtotal resection, and then had gel foam containing an adeno
      associated virus vector encoding either hIFN-beta or green fluorescence protein
      (control) placed in the resection cavity. The primary endpoint was stabilization
      of tumor vasculature, as evidenced by CD34, alpha-SMA, and CA IX staining.
      Overall survival was a secondary endpoint. RESULTS: hIFN-beta treatment altered
      the tumor vasculature of GBM6-luc and SJG2-luc xenografts, decreasing the density
      of endothelial cells, stabilizing vessels with pericytes, and decreasing tumor
      hypoxia. The mean survival for rats with these neoplasms was not improved,
      however. In rats with MT330-luc xenografts, hIFN-beta resulted in tumor
      regression with a 6-month survival of 55% (INF-beta group) and 9% (control
      group). CONCLUSION: The use of AAV hIFN-beta in our orthotopic model of
      glioblastoma resection stabilized tumor vasculature and improved survival in rats
      with MT330 xenografts.

PMID- 21878237
TI  - Impact of preoperative change in physical function on postoperative recovery:
      argument supporting prehabilitation for colorectal surgery.
AB  - BACKGROUND: Abdominal surgery represents a physiologic stress and is associated
      with a period of recovery during which functional capacity is often diminished.
      "Prehabilitation" is a program to increase functional capacity in anticipation of
      an upcoming stressor. We reported recently the results of a randomized trial
      comparing 2 prehabilitation programs before colorectal surgery (stationary
      cycling plus weight training versus a recommendation to increase walking coupled
      with breathing exercises); however, adherence to the programs was low. The
      objectives of this study were to estimate: (1) the extent to which physical
      function could be improved with either prehabilitation program and identify
      variables associated with response; and (2) the impact of change in preoperative
      function on postoperative recovery. METHODS: This study involved a reanalysis of
      data arising from a randomized trial. The primary outcome measure was functional
      walking capacity measured by the Six-Minute Walk Test; secondary outcomes were
      anxiety, depression, health-related quality of life, and complications (Clavien
      classification). Multiple linear regression was used to estimate the extent to
      which key variables predicted change in functional walking capacity over the
      prehabilitation and follow-up periods. RESULTS: We included 95 people who
      completed the prehabilitation phase (median, 38 days; interquartile range, 22
      60), and 75 who were also evaluated postoperatively (mean, 9 weeks). During
      prehabilitation, 33% improved their physical function, 38% stayed within 20 m of
      their baseline score, and 29% deteriorated. Among those who improved, mental
      health, vitality, self-perceived health, and peak exercise capacity also
      increased significantly. Women were less likely to improve; low baseline walking
      capacity, anxiety, and the belief that fitness aids recovery were associated with
      improvements during prehabilitation. In the postoperative phase, the patients who
      had improved during prehabilitation were also more likely to have recovered to
      their baseline walking capacity than those with no change or deterioration (77%
      vs 59% and 32%; P = .0007). Patients who deteriorated were at greater risk of
      complications requiring reoperation and/or intensive care management. Significant
      predictors of poorer recovery included deterioration during prehabilitation, age
      >75 years, high anxiety, complications requiring intervention, and timing of
      follow-up assessment. CONCLUSION: In a group of patients undergoing scheduled
      colorectal surgery, meaningful changes in functional capacity can be achieved
      over several weeks of prehabilitation. Patients and those who care for them,
      especially those with poor physical capacity, should consider a prehabilitation
      regimen to enhance functional exercise capacity before colectomy.

PMID- 21878239
TI  - A novel technique for postoperative perineal hernia repair.

PMID- 21878238
TI  - Gallstone pancreatitis in older patients: Are we operating enough?
AB  - BACKGROUND: The recommended therapy for mild gallstone pancreatitis is
      cholecystectomy on initial hospitalization. METHODS: Using a 5% national Medicare
      sample (1996-2005), we evaluated adherence to current recommendations for
      gallstone pancreatitis (cholecystectomy rates on initial hospitalization and the
      use of endoscopic retrograde cholangiopancreatography [ERCP]/sphincterotomy). We
      evaluated predictors of cholecystectomy, gallstone-related readmissions, and 2
      year mortality. RESULTS: Adherence to current guidelines was low. Only 57% of
      8,452 Medicare beneficiaries presenting to an acute care hospital with a first
      episode of mild gallstone pancreatitis underwent cholecystectomy on initial
      hospitalization. Of the patients who did not undergo cholecystectomy, 55% were
      never evaluated by a surgeon. Likewise, only 28% of patients who did not undergo
      cholecystectomy had a sphincterotomy. The 2-year readmission rates were higher
      among patients who did not undergo cholecystectomy (44% vs 4%; P < .0001), and
      33% of these patients required cholecystectomy after discharge. In the no
      cholecystectomy group, ERCP prevented readmissions (hazard ratio, 0.53; 95%
      confidence interval, 0.47-0.61) and when readmissions occurred they were less
      likely to be for gallstone pancreatitis in patients who had an ERCP (27.8% vs
      53.2%; P < .0001). On multivariate analysis, patients who were older, black,
      admitted to a nonsurgical service, lived in certain US regions, and had specific
      comorbidities were less likely to undergo cholecystectomy. CONCLUSION: Adherence
      to current recommendations for the management of mild gallstone pancreatitis is
      low in older patients. Our data suggest that >40% of patients who did not undergo
      cholecystectomy would have benefited from early definitive therapy.
      Implementation of policies to increase adherence to guidelines would prevent
      gallstone-related morbidity and mortality in older patients.

PMID- 21878242
TI  - Defective function at the epithelial junction: a novel therapeutic frontier in
      asthma?

PMID- 21878241
TI  - Decreased lung function after preschool wheezing rhinovirus illnesses in children
      at risk to develop asthma.
AB  - BACKGROUND: Preschool rhinovirus (RV) wheezing illnesses predict an increased
      risk of childhood asthma; however, it is not clear how specific viral illnesses
      in early life relate to lung function later on in childhood. OBJECTIVE: To
      determine the relationship of virus-specific wheezing illnesses and lung function
      in a longitudinal cohort of children at risk for asthma. METHODS: Two hundred
      thirty-eight children were followed prospectively from birth to 8 years of age.
      Early life viral wheezing respiratory illnesses were assessed by using standard
      techniques, and lung function was assessed annually by using spirometry and
      impulse oscillometry. The relationships of these virus-specific wheezing
      illnesses and lung function were assessed by using mixed-effect linear
      regression. RESULTS: Children with RV wheezing illness demonstrated significantly
      decreased spirometry values, FEV(1) (P = .001), FEV(0.5) (P < .001), FEF(25-75)
      (P < .001), and also had abnormal impulse oscillometry measures--more negative
      reactance at 5 Hz (P < .001)--compared with those who did not wheeze with RV.
      Children who wheezed with respiratory syncytial virus or other viral illnesses
      did not have any significant differences in spirometric or impulse oscillometry
      indices when compared with children who did not. Children diagnosed with asthma
      at ages 6 or 8 years had significantly decreased FEF(25-75) (P = .05) compared
      with children without asthma. CONCLUSION: Among outpatient viral wheezing
      illnesses in early childhood, those caused by RV infections are the most
      significant predictors of decreased lung function up to age 8 years in a high
      risk birth cohort. Whether low lung function is a cause and/or effect of RV
      wheezing illnesses is yet to be determined.

PMID- 21878243
TI  - Regulation of TH17 and regulatory T cells in patients with Behcet disease.

PMID- 21878244
TI  - Effect of partially hydrolyzed whey infant formula and prolonged breast-feeding
      on the risk of allergic disease in high-risk children.

PMID- 21878246
TI  - Evaluation of the child with recurrent wheezing.

PMID- 21878247
TI  - Current concepts in temporomandibular joint surgery.

PMID- 21878248
TI  - Arthroscopic anatomy and lysis and lavage of the temporomandibular joint.

PMID- 21878249
TI  - Advanced arthroscopy of the temporomandibular joint.

PMID- 21878250
TI  - Modified condylotomy for temporomandibular joint dysfunction.

PMID- 21878251
TI  - Arthroplasty and discectomy of the temporomandibular joint.

PMID- 21878252
TI  - Temporomandibular joint eminectomy for recurrent dislocation.

PMID- 21878253
TI  - Resection of the severely ankylosed temporomandibular joint.

PMID- 21878254
TI  - Total reconstruction of the temporomandibular joint with a stock prosthesis.

PMID- 21878255
TI  - Patient-fitted ("custom") alloplastic temporomandibular joint replacement
      technique.

PMID- 21878256
TI  - Planning for combined TMJ arthroplasty and orthognathic surgery.

PMID- 21878319
TI  - Kinetic, mutagenic, and structural homology analysis of L-serine dehydratase from
      Legionella pneumophila.
AB  - A structural database search has revealed that the same fold found in the
      allosteric substrate binding (ASB) domain of Mycobacterium tuberculosis D-3
      phosphoglycerate dehydrogenase (PGDH) is found in l-serine dehydratase from
      Legionella pneumophila. The M. tuberculosis PGDH ASB domain functions in the
      control of catalytic activity. Bacterial l-serine dehydratases are 4Fe-4S
      proteins that convert l-serine to pyruvate and ammonia. Sequence homology reveals
      two types depending on whether their alpha and beta domains are on the same (Type
      2) or separate (Type 1) polypeptides. The alpha domains contain the catalytic
      iron-sulfur center while the beta domains do not yet have a described function,
      but the structural homology with PGDH suggests a regulatory role. Type 1 beta
      domains also contain additional sequence homologous to PGDH ACT domains. A
      continuous assay for l-serine dehydratase is used to demonstrate homotropic
      cooperativity, a broad pH range, and essential irreversibility. Product
      inhibition analysis reveals a Uni-Bi ordered mechanism with ammonia dissociating
      before pyruvate. l-Threonine is a poor substrate and l-cysteine and d-serine are
      competitive inhibitors with K(i) values that differ by almost 10-fold from those
      reported for Escherichia colil-serine dehydratase. Mutagenesis identifies the
      three cysteine residues at the active site that anchor the iron-sulfur complex.

PMID- 21878320
TI  - Conserved GC-boxes, E-box and GATA motif are essential for GATA-4 gene expression
      in P19CL6 cells.
AB  - The promoter of the GATA-4 gene was analyzed in P19CL6 cells. A 124bp segment
      containing conserved two GC-boxes and E-box was essential for the basal promoter
      activity, as determined with a transient luciferase reporter gene assay. However,
      an extended 1312 bp reporter construct but not the 124 bp segment, when ligated
      to the GFP gene and stably inserted into the chromosome, showed regulated
      promoter activity since GFP was expressed upon DMSO addition. Mutations of the
      two GC-boxes and/or E-box significantly impaired the GFP expression. Furthermore,
      mutation of the distal conserved GATA motif in the 1312 bp sequence decreased the
      expression of GFP. Chromatin immuno-precipitation assay showed that GATA-6 binds
      to this conserved GATA motif. These results suggest that the distal GATA motif
      recognized by GATA-6 together with the GC- and E-boxes may be important for
      transcriptional activation of the GATA-4 gene in the chromosome.

PMID- 21878321
TI  - Amiodarone impairs trafficking through late endosomes inducing a Niemann-Pick C
      like phenotype.
AB  - Patients treated with amiodarone accumulate lysobisphosphatidic acid (LBPA), also
      known as bis(monoacylglycero)phosphate, in airway secretions and develop in
      different tissues vacuoles and inclusion bodies thought to originate from
      endosomes. To clarify the origin of these changes, we studied in vitro the
      effects of amiodarone on endosomal activities like transferrin recycling, Shiga
      toxin processing, ESCRT-dependent lentivirus budding, fluid phase endocytosis,
      proteolysis and exosome secretion. Furthermore, since the accumulation of LBPA
      might point to a broader disturbance in lipid homeostasis, we studied the effect
      of amiodarone on the distribution of LBPA, unesterified cholesterol,
      sphingomyelin and glycosphyngolipids. Amiodarone analogues were also studied,
      including the recently developed derivative dronedarone. We found that amiodarone
      does not affect early endosomal activities, like transferrin recycling, Shiga
      toxin processing and lentivirus budding. Amiodarone, instead, interferes with
      late compartments of the endocytic pathway, blocking the progression of fluid
      phase endocytosis and causing fusion of organelles, collapse of lumenal
      structures, accumulation of undegraded substrates and amassing of different types
      of lipids. Not all late endocytic compartments are affected, since exosome
      secretion is spared. These changes recall the Niemann-Pick type-C phenotype
      (NPC), but originate by a different mechanism, since, differently from NPC, they
      are not alleviated by cholesterol removal. Studies with analogues indicate that
      basic pKa and high water-solubility at acidic pH are crucial requirements for the
      interference with late endosomes/lysosomes and that, in this respect, dronedarone
      is at least as potent as amiodarone. These findings may have relevance in fields
      unrelated to rhythm control.

PMID- 21878323
TI  - Relative exchangeable copper: a new highly sensitive and highly specific
      biomarker for Wilson's disease diagnosis.
AB  - Wilson disease (WD) is an autosomal recessive inherited disorder of copper
      metabolism. Failure to diagnose WD can be dramatic leading to irreversible
      damages. The molecular genetic analysis of ATP7B gene is the reference test for
      diagnosis but the number of reported mutations of the ATP7B gene is on the rise.
      The analysis is cumbersome and requires tedious work. Other clinical and
      biological tests are proposed but it is often difficult to interpret some
      patients' results. A rapid and reliable biological test for WD diagnosis is still
      needed. Analytical reliability of Exchangeable copper (CuEXC) determination
      procedure is examined by studying the repeatability, the short term stability and
      stability in frozen serum. Relative exchangeable copper (REC=CuEXC/total copper%)
      is proposed and evaluated as a new diagnostic test and compared to classic tests
      used for WD diagnosis. Sixteen new Wilson disease patients were diagnosed in our
      institution between January 2009 and May 2011. The different biological tests
      used for WD diagnosis yielded lower sensitivity and specificity compared to our
      new biomarker, the REC. We show that REC is an excellent discriminatory tool for
      the diagnosis of WD offering 100% sensitivity and 100% specificity.

PMID- 21878322
TI  - Catabolism of 4-hydroxy-2-trans-nonenal by THP1 monocytes/macrophages and
      inactivation of carboxylesterases by this lipid electrophile.
AB  - Oxidative stress in cells and tissues leads to the formation of an assortment of
      lipid electrophiles, such as the quantitatively important 4-hydroxy-2-trans
      nonenal (HNE). Although this cytotoxic aldehyde is atherogenic the mechanisms
      involved are unclear. We hypothesize that elevated HNE levels can directly
      inactivate esterase and lipase activities in macrophages via protein adduction,
      thus generating a biochemical lesion that accelerates foam cell formation and
      subsequent atherosclerosis. In the present study we examined the effects of HNE
      treatment on esterase and lipase activities in human THP1 monocytes/macrophages
      at various physiological scales (i.e., pure recombinant enzymes, cell lysate, and
      intact living cells). The hydrolytic activities of bacterial and human
      carboxylesterase enzymes (pnbCE and CES1, respectively) were inactivated by HNE
      in vitro in a time- and concentration-dependent manner. In addition, so were the
      hydrolytic activities of THP1 cell lysates and intact THP1 monocytes and
      macrophages. A single lysine residue (Lys105) in recombinant CES1 was modified by
      HNE via a Michael addition reaction, whereas the lone reduced cysteine residue
      (Cys389) was found unmodified. The lipolytic activity of cell lysates and intact
      cells was more sensitive to the inhibitory effects of HNE than the esterolytic
      activity. Moreover, immunoblotting analysis using HNE antibodies confirmed that
      several cellular proteins were adducted by HNE following treatment of intact THP1
      monocytes, albeit at relatively high HNE concentrations (>50MUM). Unexpectedly,
      in contrast to CES1, the treatment of a recombinant human CES2 with HNE enhanced
      its enzymatic activity ~3-fold compared to untreated enzyme. In addition, THP1
      monocytes/macrophages can efficiently metabolize HNE, and glutathione conjugation
      of HNE is responsible for ~43% of its catabolism. The functional importance of
      HNE-mediated inactivation of cellular hydrolytic enzymes with respect to
      atherogenesis remains obscure, although this study has taken a first step toward
      addressing this important issue by examining the potential of HNE to inhibit this
      biochemical activity in a human monocyte/macrophage cell line.

PMID- 21878324
TI  - High p27 expression is associated with a better prognosis in East Asian non-small
      cell lung cancer patients.
AB  - BACKGROUND: The role of the anti-apoptotic protein p27 in non-small cell lung
      cancer (NSCLC) remains controversial. To clarify its association with survival in
      NSCLC, we performed a systematic review of the literature with meta-analysis.
      METHODS: Trials were selected for further analysis if they provided an
      independent assessment of p27 in NSCLC and reported the analysis of survival data
      based on p27 status. A total of 11 trials, which comprised 1646 patients,
      provided sufficient information for the meta-analysis. Sensitivity analyses were
      conducted using histology, disease stage and ethnicity. RESULTS: The combined
      hazard ratio (HR) of 1.50 (95% CI=1.15-1.97; P<0.001 for heterogeneity) suggested
      that high p27 expression has a favorable impact on survival. When the studies
      were restricted to those of East Asian populations, patients that expressed high
      levels of p27 showed a better survival rate (HR 1.73, 95% CI=1.36-2.21; P=0.169
      for heterogeneity) than those that did not express high levels of p27. In
      addition, the heterogeneity and publication bias disappeared. CONCLUSION: In
      NSCLC, high p27 expression is associated with a better prognosis among East
      Asians.

PMID- 21878325
TI  - Enhancement of supercooling capacity and survival by cold acclimation, rapid cold
      and heat hardening in Spodoptera exigua.
AB  - Insects can increase their resistance to cold stress by prior exposure to non
      lethal cold temperatures. Here, we investigated the supercooling capacity and
      survival of eggs, 3rd and 5th instar larvae, and pupae of Spodoptera exigua
      (Lepidoptera: Noctuidae) during CA, and responses to various pre-treatment
      protocols, including constant temperatures, thermoperiods, and RCH, RHH, RCH+RHH
      and RHH+RCH combined with thermoperiods. Only acclimated eggs demonstrated a
      significant decrease in SCP, from -20.7+/-0.3 to -22.9+/-0.3 degrees C, among all
      experimental groups compared to non-acclimated stages. Survival increased by
      17.5% for eggs, 40.0% and 13.3% for 3rd and 5th instar larvae, and by 20.0% for
      pupae after CA. Compared to controls, survival of eggs under the conditions of
      thermoperiod (5:15 degrees C), thermoperiod (5:15 degrees C)+RHH, and
      thermoperiod (5:15, 10:20, and 15:25 degrees C)+RCH significantly increased. In
      addition, survival of 3rd and 5th instar larvae and pupae increased under the
      conditions of thermoperiod (5:15 degrees C) and thermoperiod (5:15 degrees
      C)+RCH, possibly due to the induction of heat shock proteins or cryoprotectants.
      However, the pre-treatments of thermoperiod+RCH+RHH and thermoperiod+RHH+RCH did
      not significantly enhance survival of any developmental stage. These adaptive
      responses may allow S. exigua to enhance supercooling capacity and survival in
      response to seasonal or unexpected diurnal decreases in environmental
      temperatures.

PMID- 21878326
TI  - The subpopulation of mesenchymal stem cells that differentiate toward
      cardiomyocytes is cardiac progenitor cells.
AB  - Mesenchymal stem cells (MSCs) are regarded as a promising source of cell-based
      therapy for heart injury. In fact, less than 30% of MSCs contribute to
      cardiomyocytes differentiation, and the isolation procedure and biological
      characteristics of this population of cells remain unknown. Here we isolate and
      investigate the biological characteristics of this subpopulation of MSCs. Twenty
      four MSC clones were randomly selected using single-cell monoclonal technology.
      After induced with 5-azacytidine, eight clones displayed cardiomyocyte-like
      morphologies, and highly (over 90%) expressed cardiac-specific markers cTnT and
      alpha-actin, and displayed transient outward K(+) current (I(to)), inwardly
      rectifying K(+) current (I(K1)) and delayed rectifier K(+) current (I(KDR)),
      which were typical of cardiomocytes. Other clones merely showed I(to) current,
      and the current densities were different from those of cardiomyocytes. In
      contrast to the other clones, before induced with 5-azacytidine, the eight clones
      expressed early cardiac markers GATA4 and NKX2.5, but not cTnT, alpha-actin, CD44
      and CD90, and had no potentials for adiopogenesis, osteogenesis or chondrogenesis
      after induction. Our data suggest that the subgroup of MSCs that contributes to
      cardiomyocytes differentiation is cardiac progenitor cells. Moreover, we show the
      preliminary purification of this population of cells with a high potential for
      cardiomyocytes differentiation using single-cell monoclonal technology.

PMID- 21878327
TI  - Recent advances in cytochrome bc(1): inter monomer electronic communication?
AB  - The ubihydroquinone: cytochrome c oxidoreductase, or cytochrome bc(1), is a
      central component of photosynthetic and respiratory energy transduction pathways
      in many organisms. It contributes to the generation of membrane potential and
      proton gradient used for cellular energy production (ATP). The three-dimensional
      structures of cytochrome bc(1) indicate that its two monomers are intertwined to
      form a symmetrical homodimer. This unusual architecture raises the issue of
      whether the monomers operate independently, or function cooperatively during the
      catalytic cycle of the enzyme. In this review, recent progresses achieved in our
      understanding of the mechanism of function of dimeric cytochrome bc(1) are
      presented. New genetic approaches producing heterodimeric enzymes, and emerging
      insights related to the inter monomer electron transfer between the heme b
      cofactors of cytochrome bc(1) are described.

PMID- 21878328
TI  - E3 ubiquitin ligase Siah-1 facilitates poly-ubiquitylation and proteasomal
      degradation of the hepatitis B viral X protein.
AB  - Hepatitis B viral X protein (HBx) is a multifunctional transactivator and
      implicated in hepatitis B virus (HBV) replication and hepatocarcinogenesis. HBx
      can be ubiquitinated and degraded through ubiquitin-proteasome pathway. However,
      the E3 ubiquitin ligase regulating HBx ubiquitin-dependent degradation is still
      unknown. In this study, we identified Siah-1 as a novel E3 ubiquitin ligase for
      HBx, which interacted with HBx and facilitated HBx poly-ubiquitylation and
      proteasomal degradation. Co-expression of Siah-1 attenuated the transcriptional
      transactivation of HBx on glucocorticoid response element (GRE), heat shock
      response element (HSE) and cAMP response element (CRE) signal pathways. Moreover,
      Siah-1 participated in p53-mediated HBx degradation. Therefore, Siah-1 may play
      important roles in ubiquitin-dependent degradation of HBx and may be involved in
      suppressing the progression of hepatocellular carcinoma (HCC).

PMID- 21878329
TI  - An unusual cause of abdominal distension in a 4-year-old boy. Neuronal intestinal
      dysplasia.

PMID- 21878330
TI  - A palpable abdominal mass presenting as acute abdomen. Diagnosis: Jejunogastric
      intussusception.

PMID- 21878331
TI  - Cholangioscopy and probe-based confocal laser endomicroscopy in the diagnosis of
      an unusual liver cyst. Diagnosis: Biliary intraductal papillary mucinous
      neoplasia.

PMID- 21878333
TI  - Unusual colon polyps. Diagnosis: Cap polyposis.

PMID- 21878334
TI  - Effects of sex steroids on indices of protein turnover in rainbow trout
      (Oncorhynchusmykiss) white muscle.
AB  - Effects of 17beta-estradiol (E2), testosterone, and 5alpha-dihydrotestosterone
      (DHT) on protein turnover and proteolytic gene expression were determined in
      rainbow trout (Oncorhynchus mykiss) primary myocytes and white muscle tissue. E2
      reduced rates of protein synthesis and increased rates of protein degradation in
      primary myocytes by 45% and 27%, respectively. DHT reduced rates of protein
      synthesis by 27%. Testosterone did not affect protein synthesis and neither
      testosterone nor DHT affected rates of protein degradation. Single injections of
      E2 increased expression of ubiquitin ligase genes fbxo32, fbxo25, and murf1, and
      the proteasome subunit psmd6 by 24h after injection. Within the cathepsin
      lysosome pathway, E2 increased expression of cathepsins ctsd and ctsl, as well as
      autophagy-related genes atg4b and lc3b. Additionally, E2 injection up-regulated
      the expression of casp3 and casp9 caspase genes. Incubation of primary myocytes
      with E2 also increased expression of ubiquitin ligase genes. Therefore, catabolic
      effects of E2 on protein turnover result in part from E2-induced increases in
      proteolytic gene expression directly in muscle. Injection of testosterone
      increased milli-calpain (capn2) and casp3 expression, and DHT increased ctsd
      expression in vivo, whereas both androgens up-regulated fbxo32 expression in
      primary myocytes. These results suggest that effects of androgens on protein
      turnover in muscle are not driven primarily by direct effects of these hormones
      in this tissue.

PMID- 21878335
TI  - Two chicken neuromedin U receptors: characterization of primary structure,
      biological activity and tissue distribution.
AB  - Neuromedin U (NMU) is a bioactive peptide that is involved in a variety of
      physiological functions. Two of its receptors, NMUR1 and NMUR2, have been
      identified and characterized in mammals. In this study, we performed cDNA cloning
      of chicken NMUR1 and NMUR2, and characterized their primary structure, biological
      activity, and expression patterns in chicken tissues. The chicken NMUR1 and NMUR2
      cDNAs encoded 438 and 395 amino acid sequences, respectively. Chicken NMUR1
      showed 54.8%-56.5% sequence identity with human, rat, and mouse NMUR1, and NMUR2
      shared 67.3%-70.1% sequence identity with mammalian orthologs. Both chicken
      receptors have typical characteristics of G-protein-coupled receptors with seven
      transmembrane domains and the D/ERY motif. An increase in intracellular Ca(2+)
      mobilization was observed in HEK293 cells transfected with chicken NMUR1 or NMUR2
      cDNA and treated with chicken or rat NMU. Real-time PCR analysis revealed that
      NMUR1 mRNA was preferentially expressed in the intestinal tissues such as the
      duodenum, jejunum, ileum, cecum, and colon/rectum, and brain regions such as the
      midbrain and optic lobe, and the ovary in adult hens. NMUR2 mRNA was exclusively
      expressed in the brain regions such as the cerebrum and midbrain. These results
      indicate that NMUR1 and NMUR2 mRNAs, which encode functional receptor proteins,
      are expressed in chicken tissues with different distribution patterns.

PMID- 21878336
TI  - Production, characterization and utility of a panel of monoclonal antibodies for
      the detection of toluene diisocyanate haptenated proteins.
AB  - Diisocyanates (dNCOs) are highly reactive low molecular weight chemicals used in
      the manufacture of polyurethane products and are the most commonly reported cause
      of occupational asthma. Mechanistic disease studies and development of
      biomonitoring and research tools, such as monoclonal antibodies (mAbs) have been
      hampered by dNCOs' ability to self-polymerize and to cross-link biomolecules.
      Toluene diisocyanate (TDI)-specific monoclonal antibodies (mAbs), with potential
      use in immunoassays for exposure and biomarker assessments, were produced and
      reactivities characterized against mono- and diisocyanate and dithioisocyanate
      protein conjugates. In general, TDI reactive mAbs displayed stronger recognition
      of isocyanate haptenated proteins when the NCO was in the ortho position relative
      to the tolyl group, and were capable of discriminating between isocyanate and
      isothiocyanate conjugates and between aromatic and aliphatic dNCOs. Preliminary
      studies using TDI vapor exposed cells suggest potential utility of these mAbs for
      both research and biomonitoring.

PMID- 21878337
TI  - Cell activation by CpG ODN leads to improved electrofusion in hybridoma
      production.
AB  - Hybridoma formation is an indispensable step in the production of monoclonal
      antibodies. Obtaining highly efficient fusion of an antibody-producing cell to
      the myeloma cell to form the hybridoma is an important step in this process. The
      electrofusion method is superior to chemical fusion methods such as the
      polyethylene glycol (PEG) method due to its high fusion efficiency. However, this
      method requires cell activation prior to electrofusion, a process that is time
      consuming and tends to cause cell death. In this study, we achieved much higher
      fusion efficiency by stimulating B cells with CpG oligodeoxynucleotide (CpG ODN)
      over shorter periods. Splenocytes were isolated from immunized mice and cultured
      in the presence of a CpG ODN for 1 or 2 days. This CpG ODN stimulation evokes
      about one order of magnitude higher fusion efficiency than other stimulators. CpG
      ODN stimulation not only increases the fusion efficiency but also the number of
      antibody-producing cells. This leads to a substantial increase in the number of
      positive clones obtained. This highly efficient fusion method was used to produce
      a functional antibody against Gaussia luciferase. This method was found to
      produce greater numbers of hybridomas and to enable direct screening for
      antibodies with functional characteristics such as inhibition of the luminescence
      activity of an antigen. We were able to establish a functional antibody against
      Gaussia luciferase after a single fusion experiment using our electrofusion
      method.

PMID- 21878338
TI  - Cryopreservation of monocytes or differentiated immature DCs leads to an altered
      cytokine response to TLR agonists and microbial stimulation.
AB  - Literature on the effects of cryopreservation and thawing of monocytes or
      monocyte-derived immature dendritic cells (iDCs) on the subsequent functional
      capacities of the DCs is limited to a few specific maturation stimuli and is
      focused on applications in clinical immunotherapy. Given the cardinal role of DCs
      in regulating tolerance and immunity at mucosal surfaces there is a growing
      interest in understanding the effect of stromal, microbial and probiotic signals
      on DC function. Therefore our aim was to investigate the effects of
      cryopreservation on the functional properties of DCs stimulated with bacteria or
      the bacterial components using a standardized method. Surface markers CD83 and
      CD86 were expressed at similar levels on iDCs generated from cryopreserved or
      freshly isolated monocytes. Cryopreservation of iDCs led to slightly decreased
      expression of CD86 and CD83 compared to freshly generated iDCs prepared from
      unfrozen cells but this did not affect the capacity of DCs to acquire fully
      mature characteristics after stimulation. In contrast the cytokine response to
      lipoteichoic acid and bacterial stimulation was altered by cryopreservation of
      monocytes or iDCs, particularly for IL-12p70 which was decreased up to 250 fold
      or not detected. Cryopreservation also decreased TNF-alpha and IL-1beta
      production in stimulated iDCs but to a lesser extent than for IL-12p70, depending
      on the maturation factors used. The amounts of IL-10 produced by stimulated iDCs
      were increased up to 3.6 fold when iDCs were cryopreserved, but decreased up to
      90 fold when generated from cryopreserved monocytes. Immature DCs are often used
      to investigate the immunomodulatory properties of probiotics and here we show for
      the first time that cryopreserved monocytes and cryopreserved iDCs have a skewed
      cytokine response to microbial stimulation. These findings have implications for
      the methods used in bacterial-DC immune assays and highlight the importance of
      comparing different cytokines and stimuli in immune cell cryopreservation
      protocols.

PMID- 21878339
TI  - Triacylglyceride measurement in small quantities of homogenised insect tissue:
      comparisons and caveats.
AB  - Triacylglycerides (TAGs) are the most important stored energy reserve in
      eukaryotes and are regularly measured in insects. Quantitative analysis of TAGs
      is complicated by their diversity of structure, and there are concerns with the
      quantitative accuracy of commonly used analytical methods. We used thin layer
      chromatography coupled to a flame ionisation detector (TLC-FID), an accurate
      method that is not sensitive to saturation or chain length of fatty acids, to
      quantify TAG content in small amounts of insect tissue, and used it to validate
      three high-throughput lipid assays (gravimetric, vanillin, and enzymatic). The
      performance of gravimetric assays depended on the solvent used. Folch reagent
      (chloroform: methanol 2:1 v/v) was a good index of TAG content, but overestimated
      lipid content due to the extraction of structural lipid and non-lipid components.
      Diethyl ether produced reasonable quantitative measurements but lacked precision
      and could not produce a repeatable rank-order of samples. The vanillin assay was
      accurate both as a quantitative method and as an index, preferably with a
      standard of mixed fatty acid composition. The enzymatic assay did not accurately
      or precisely quantify TAGs under our assay conditions. We conclude that the
      vanillin assay is suitable as a high-throughput method for quantifying TAG
      providing fatty acid composition does not change among treatment groups. However,
      if samples contain significant quantities of di- or mono-acylglycerides, or the
      fatty acid composition differs across treatment groups, TLC-FID is recommended.

PMID- 21878341
TI  - Alterations in anxiety-like behavior following knockout of the uncoupling protein
      2 (ucp2) gene in mice.
AB  - AIMS: Uncoupling protein 2 (UCP2) is a mitochondrial protein that reduces
      oxidative stress and has a protective function in chronic inflammatory diseases
      such as multiple sclerosis, rheumatoid arthritis and systemic lupus
      erythematosus. UCP2 is strongly expressed in areas implicated in the central
      regulation of stress and anxiety. Therefore, we compared the neuroendocrine
      regulation of stress responses, immunity and behavior in UCP2-deficient and
      wildtype C57BL/6J mice under psychological stress. MAIN METHODS: Stress was
      induced by social disruption (SDR) and anxiety-like behavior was examined using
      the elevated plus-maze (EPM). Serum corticosterone was determined by
      radioimmunoassay and brain neurotransmitter concentrations were analyzed by HPLC
      of whole brain homogenates. T cell activation and tumor necrosis factor (TNF)
      alpha production of mitogen-activated splenocytes were determined in vitro by
      flow cytometry staining of CD25, CD69 and CD71 on CD4 cells, and ELISA,
      respectively. The influence of corticosterone on UCP2 expression of splenocytes
      was analyzed by Western blot. KEY FINDINGS: At baseline, UCP2-deficient mice were
      significantly more anxious in the EPM than wildtype mice, and this phenotype was
      exacerbated after SDR stress. The corticosterone response after SDR+EPM was
      reduced in UCP2-deficient mice compared to wildtype mice. Corticosterone in turn
      downregulates UCP2 expression in splenocyte cultures of wildtype mice at
      physiological concentrations. Dopaminergic and serotonergic turnovers were
      increased in UCP2-deficient mice after SDR+EPM. While T-helper cell activation
      marker expression was reduced, TNF-alpha production was increased in UCP2
      deficient mice after SDR+EPM. SIGNIFICANCE: Our study shows that UCP2 is involved
      in anxiety-like behavior and modulates neuroendocrine and immune responses after
      stress.

PMID- 21878342
TI  - M3-receptor activation counteracts opioid-mediated apneusis, but the apneusis per
      se is not necessarily related to an impaired M3 mechanism in rats.
AB  - AIMS: Morphine slows the respiratory cycle due to a predominant prolongation of
      inspiration (apneusis) by postponing the spontaneous termination of inspiration
      (inspiratory off-switching). The present study investigates whether the morphine
      induced apneusis results from impairment of cholinergic mechanisms in the central
      respiratory network. MAIN METHODS: The efferent discharge was recorded from the
      phrenic nerve in artificially ventilated and anesthetized rats with vagotomy. All
      drugs were injected intravenously. KEY FINDINGS: The phrenic nerve displayed an
      augmenting discharge during inspiration and arrest of discharge during expiration
      in normal condition. Administration of morphine (0.3-10.0mg/kg) dose-dependently
      provoked apneusis characterized by a long-lasting, plateau inspiratory discharge
      of the phrenic nerve. It shortened the expiratory duration. Subsequent
      administration of physostigmine (0.1mg/kg) restored the morphine-induced apneusis
      to eupnea with a partial recovery of the augmenting inspiratory discharge. This
      modification of physostigmine was blocked by a non-specific muscarinic antagonist
      scopolamine (3.0mg/kg), leading to re-prolongation of inspiration. A similar
      antagonism was affected by an antagonist of M3 cholinergic receptors, 4
      diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, 1.0 and 10.0mg/kg) but not
      by an antagonist of M1 cholinergic receptors, pirenzepine (1.0 and 10.0mg/kg).
      SIGNIFICANCE: These results demonstrate that the activation of endogenous M3
      cholinergic mechanisms counteracts the morphine-induced apneusis.

PMID- 21878340
TI  - Protein O-linked beta-N-acetylglucosamine: a novel effector of cardiomyocyte
      metabolism and function.
AB  - The post-translational modification of serine and threonine residues of nuclear
      and cytoplasmic proteins by the O-linked attachment of the monosaccharide beta-N
      acetyl-glucosamine (O-GlcNAc) is emerging as an important mechanism for the
      regulation of numerous biological processes critical for normal cell function.
      Active synthesis of O-GlcNAc is essential for cell viability and acute activation
      of pathways resulting in increased protein O-GlcNAc levels improves the tolerance
      of cells to a wide range of stress stimuli. Conversely sustained increases in O
      GlcNAc levels have been implicated in numerous chronic disease states, especially
      as a pathogenic contributor to diabetic complications. There has been increasing
      interest in the role of O-GlcNAc in the heart and vascular system and acute
      activation of O-GlcNAc levels have been shown to reduce ischemia/reperfusion
      injury, attenuate vascular injury responses as well mediate some of the
      detrimental effects of diabetes and hypertension on cardiac and vascular
      function. Here we provide an overview of our current understanding of pathways
      regulating protein O-GlcNAcylation, summarize the different methodologies for
      identifying and characterizing O-GlcNAcylated proteins and subsequently focus on
      two emerging areas: 1) the role of O-GlcNAc as a potential regulator of cardiac
      metabolism and 2) the cross talk between O-GlcNAc and reactive oxygen species.
      This article is part of a Special Section entitled "Post-translational
      Modification."

PMID- 21878343
TI  - Telomeres and lifestyle factors: roles in cellular aging.
AB  - Recent research has demonstrated that telomere maintenance might be a key
      integrating point for the cumulative effects of genetic, environmental and
      lifestyle factors on aging and aging-related diseases. It is timely to 'take
      stock' of where this work has led the field. This review summarizes studies that
      have examined associations between lifestyle factors and telomere length and
      telomerase activity. In most of the studies described in this chapter, telomere
      length was measured in leukocytes (LTL) or peripheral blood mononuclear cells
      (PBMCs), taken from blood draws from the study subjects. Much of this chapter
      focuses on psychological stress, a widespread factor often intimately tied in
      with lifestyle or behavioral factors that in turn are related to risks of
      clinical diseases. Together, these findings suggest that cellular aging is linked
      to a range of influences, with an individual's life events and lifestyle
      parameters playing significant roles. Lastly, we propose possible biochemical
      mechanisms that mediate these associations and discuss future directions.

PMID- 21878345
TI  - Downregulation of the immune system in low-quality child care: the case of
      secretory immunoglobulin A (SIgA) in toddlers.
AB  - Does the experience of stress during child care lead to downregulation of the
      immune system, in particular in low-quality care? Saliva was collected from 68
      toddlers attending center or family child care at home and at child care, and
      assayed for secretory IgA (SIgA). Caregiver sensitivity was used as an index of
      quality of care and was observed during three videotaped episodes of 10 min.
      Diurnal patterns of SIgA showed a steep fall in the morning followed by a
      flattening out. SIgA was not associated with type of care, but lower caregiver
      sensitivity was associated with lower SIgA levels in both types of care. Quality
      of child care is associated with a non-specific secretory component of children's
      mucosal immunity with well established protective effects against upper
      respiratory infections.

PMID- 21878344
TI  - Nicotinic excitatory postsynaptic potentials in hippocampal CA1 interneurons are
      predominantly mediated by nicotinic receptors that contain alpha4 and beta2
      subunits.
AB  - In the hippocampus, activation of nicotinic receptors that include alpha4 and
      beta2 subunits (alpha4beta2*) facilitates memory formation. alpha4beta2*
      receptors may also play a role in nicotine withdrawal, and their loss may
      contribute to cognitive decline in aging and Alzheimer's disease (AD). However,
      little is known about their cellular function in the hippocampus. Therefore,
      using optogenetics, whole cell patch clamping and voltage-sensitive dye (VSD)
      imaging, we measured nicotinic excitatory postsynaptic potentials (EPSPs) in
      hippocampal CA1. In a subpopulation of inhibitory interneurons, release of ACh
      resulted in slow depolarizations (rise time constant 33.2 +/- 6.5 ms, decay time
      constant 138.6 +/- 27.2 ms) mediated by the activation of alpha4beta2* nicotinic
      receptors. These interneurons had somata and dendrites located in the stratum
      oriens (SO) and stratum lacunosum-moleculare (SLM). Furthermore, alpha4beta2*
      nicotinic EPSPs were largest in the SLM. Thus, our data suggest that nicotinic
      EPSPs in hippocampal CA1 interneurons are predominantly mediated by alpha4beta2*
      nicotinic receptors and their activation may preferentially affect
      extrahippocampal inputs in SLM of hippocampal CA1.

PMID- 21878346
TI  - Effects of ascorbic acid on carcinogenicity and acute toxicity of nickel
      subsulfide, and on tumor transplants growth in gulonolactone oxidase knock-out
      mice and wild-type C57BL mice.
AB  - The aim of this study was to test a hypothesis that ascorbate depletion could
      enhance carcinogenicity and acute toxicity of nickel. Homozygous L-gulono-<gamma>
      lactone oxidase gene knock-out mice (Gulo-/- mice) unable to produce ascorbate
      and wild-type C57BL mice (WT mice) were injected intramuscularly with
      carcinogenic nickel subsulfide (Ni3S2), and observed for the development of
      injection site tumors for 57 weeks. Small pieces of one of the induced tumors
      were transplanted subcutaneously into separate groups of Gulo-/- and WT mice and
      the growth of these tumors was measured for up to 3 months. The two strains of
      mice differed significantly with regard to (1) Ni3S2 carcinogenesis: Gulo-/- mice
      were 40% more susceptible than WT mice; and (2) transplanted tumors development:
      Gulo-/- mice were more receptive to tumor growth than WT mice, but only in terms
      of a much shorter tumor latency; later in the exponential phase of growth, the
      growth rates were the same. And, with adequate ascorbate supplementation, the two
      strains were equally susceptible to acute toxicity of Ni3S2. Statistically
      significant effects of dietary ascorbate dosing levels were the following: (1)
      reduction in ascorbate supplementation increased acute toxicity of Ni3S2 in Gulo
      /- mice; (2) ascorbate supplementation extended the latency of transplanted
      tumors in WT mice. In conclusion, the lack of endogenous ascorbate synthesis
      makes Gulo-/- mice more susceptible to Ni3S2 carcinogenesis. Dietary ascorbate
      tends to attenuate acute toxicity of Ni3S2 and to extend the latency of
      transplanted tumors. The latter effects may be of practical importance to humans
      and thus deserve further studies.

PMID- 21878347
TI  - Some properties and cDNA cloning of proteinaceous toxins from two species of
      lionfish (Pterois antennata and Pterois volitans).
AB  - Lionfish, members of the genera Pterois, Parapterois and Dendrochirus, are well
      known to be venomous, having venomous glandular tissues in dorsal, pelvic and
      anal spines. The lionfish toxins have been shown to cross-react with the
      stonefish toxins by neutralization tests using the commercial stonefish
      antivenom, although their chemical properties including structures have been
      little characterized. In this study, an antiserum against neoverrucotoxin, the
      stonefish Synanceia verrucosa toxin, was first raised in a guinea pig and used in
      immunoblotting and inhibition immunoblotting to confirm that two species of
      Pterois lionfish (P. antennata and P. volitans) contain a 75kDa protein
      (corresponding to the toxin subunit) cross-reacting with neoverrucotoxin. Then,
      the amino acid sequences of the P. antennata and P. volitans toxins were
      successfully determined by cDNA cloning using primers designed from the highly
      conserved sequences of the stonefish toxins. Notably, either alpha-subunits (699
      amino acid residues) or beta-subunits (698 amino acid residues) of the P.
      antennata and P. volitans toxins share as high as 99% sequence identity with each
      other. Furthermore, both alpha- and beta-subunits of the lionfish toxins exhibit
      high sequence identity (70-80% identity) with each other and also with the beta
      subunits of the stonefish toxins. As reported for the stonefish toxins, the
      lionfish toxins also contain a B30.2/SPRY domain (comprising nearly 200 amino
      acid residues) in the C-terminal region of each subunit.

PMID- 21878348
TI  - Towards a better understanding of Ipomoea asarifolia toxicity: evidence of the
      involvement of a leaf lectin.
AB  - Natural intoxication of livestock by ingestion of Ipomoea asarifolia leaves has
      been reported to occur widely in Brazil. Previous studies carried out by our
      research group provided strong evidence that a lectin could be involved with the
      toxic properties of I. asarifolia. To reinforce this hypothesis, a lectin
      enriched fraction (LEF) was isolated from I. asarifolia leaves and its toxic
      effects were assessed. Leaves of I. asarifolia were excised from plants growing
      widely in the field, mechanically wounded and maintained in a chamber at 25 +/- 3
      degrees C for 72h in the dark, under near 100% relative humidity. The leaf
      proteins were extracted, ammonium sulfate precipitated, chromatographed on DEAE
      cellulose and Phenyl-Sepharose to produce LEF that under SDS-PAGE showed a
      molecular mass of 44.0 kDa and after N-terminal amino acid analysis a primary
      sequence composed of AGYTPVLDIGAEVLAAGEPY. The in vivo toxicity of LEF assessed
      by intraorbital injection in mice showed induced severe uncoordinated movements
      without death. LEF reduced the muscular contraction in a dose depend way and at
      29.8 MUg/mL (CE(50)) it produces 50% inhibition of contraction, suggesting that
      LEF blunts autonomic neurotransmission. Isolated rat kidneys were perfused with
      LEF and no effects on the perfusion pressure or renal vascular resistance were
      observed, but urinary flow and glomerular filtration rate increased. Moreover,
      the percentage of tubular transport of Na(+), K(+) and Cl(-) decreased.
      Histological examination of the kidneys perfused with LEF exhibited little
      alterations. These toxic effects observed above were concomitant with the
      increase of LEF hemagglutination activity, which strongly suggest that one of the
      toxic principles of I. asarifolia is a lectin present in its leaves.

PMID- 21878349
TI  - Oxidatively modified nucleic acids in preclinical Alzheimer's disease (PCAD)
      brain.
AB  - Previous studies show increased oxidative DNA and RNA damage and diminished 8
      oxoguanine glycosylase (OGG1) mediated base excision repair in vulnerable brain
      regions of mild cognitive impairment and late-stage Alzheimer's disease (LAD)
      subjects compared to normal control (NC) subjects. Recently, a preclinical stage
      of AD (PCAD) has been described in which subjects show no overt clinical
      manifestations of AD but demonstrate significant AD pathology at autopsy. To
      determine if DNA or RNA oxidation are significantly elevated in PCAD brain we
      quantified 8-hydroxyguanine (8-OHG) in sections of hippocampus/parahippocamapal
      gyri in PCAD and NC subjects using immunohistochemistry and confocal microscopy
      and in superior and middle temporal gyri (SMTG) using gas chromatography/mass
      spectrometry. To determine if increased DNA oxidation is associated with altered
      repair capacity, levels of OGG1 protein in HPG were measured by
      immunohistochemistry and levels of OGG1 mRNA were measured in SMTG using
      quantitative PCR. Results show significantly increased (p<0.05) 8-OHG
      immunostaining in DNA and RNA of PCAD HPG and significantly increased 8-OHG in
      PCAD SMTG. Quantification of OGG1 showed significantly elevated mRNA in PCAD SMTG
      and a trend toward elevated protein immunostaining in PCAD HPG. Overall, the data
      suggest oxidative damage to nucleic acids and a compensatory increase in OGG1
      expression occur early in the pathogenesis of AD.

PMID- 21878351
TI  - Correlates of moderate-to-vigorous physical activity among preschoolers during
      unstructured outdoor play periods.
AB  - OBJECTIVE: Quantify moderate-to-vigorous physical activity (MVPA) and its
      correlates in preschool children during outdoor unstructured play periods using
      direct observation. METHODS: Cross-sectional data consisting of 204 observation
      periods collected from 51 four- and five-year-old children using the Observation
      System for Recording Physical Activity in Children - Preschool (OSRAC-P) at a
      preschool in southern California, autumn and spring 2009-2010. Gender and BMI
      classification and OSRAC-P environmental codes were related to observed MVPA in
      multiple logistic regression models. RESULTS: Less than 21% of intervals were
      spent in MVPA overall. Boys and normal weight children engaged in higher
      intensity levels than their respective counterparts. More MVPA was associated
      with normal weight (OR=2.49-3.25, R(2)=3%), location (grass, playground, looping
      cycle path; OR=3.21-4.90, R(2)=4-12%), play context (ball/objects, wheel, open
      space; OR=2.78-8.51, R(2)=9%), and group composition (solitary, one-on-one;
      OR=1.34-2.08, R(2)=1%). CONCLUSION: Open spaces located in playgrounds and grass
      fields, and activity-genic portable equipment, manipulative objects, and riding
      vehicles are some design and equipment features that appear to foster MVPA.
      Lowering play space density and engaging children through teacher prompts and
      teacher-arranged activities may further increase MVPA on playgrounds.

PMID- 21878350
TI  - Minimal structural requirements of alkyl gamma-lactones capable of antagonizing
      the cocaine-induced motility decrease in planarians.
AB  - We recently reported that the natural cyclic lactone, parthenolide, and related
      analogs prevent the expression of behavioral effects induced by cocaine in
      planarians and that parthenolide's gamma-lactone ring is required for this
      effect. In the present work, we tested a series of alkyl gamma-lactones with
      varying chain length (1-8 carbons) to determine their ability to antagonize the
      planarian motility decrease induced by 200 MUM cocaine. Alkyl lactones with up to
      a 4-carbon alkyl chain did not affect planarian motility or antagonized the
      cocaine-induced motility decrease; only the compound gamma-nonalactone (a gamma
      lactone with a 5-carbon chain) was able to prevent the cocaine-induced behavioral
      patterns, while alkyl lactones with longer carbon chains failed to prevent the
      cocaine-induced effects. Thus, we conclude that the optimal structural features
      of this family of compounds to antagonize cocaine's effect in this experimental
      system is a gamma-lactone ring with at a 5-carbon long functional group.

PMID- 21878352
TI  - Time jitter of somatosensory evoked potentials in recovery from hypoxic-ischemic
      brain injury.
AB  - Impaired neural conductivity shown by delayed latency and reduced amplitude of
      characteristic peaks in somatosensory evoked potentials (SSEPs), has been used to
      monitor hypoxic-ischemic brain injury after cardiac arrest (CA). However, rather
      than characteristic peak deferral and suppression, the time jitter of the peak in
      SSEP related with time-variant neurological abnormalities is diminished by the
      commonly used ensemble average method. This paper utilizes the second order blind
      identification (SOBI) technique to extract characteristic peak information from
      one trial of SSEPs. Sixteen male Wistar rats were subjected to 7 or 9 min of
      asphyxial CA (n=8 per group). The SSEPs from median nerve stimulation were
      recorded for 4h after CA and then for 15 min periods at 24, 48 and 72 h.
      Neurological outcomes were evaluated by neurologic deficit score (NDS) at 72 h
      post-CA. The SSEP signal was analyzed offline with SOBI processing in Matlab. The
      N10 feature of SSEP was compared between good (NDS>=50) and bad (NDS<50)
      outcomes. After processed by SOBI, the N10 detection rate was significantly
      increased (p<0.001) from 90 min post-CA. Statistical difference of the latency
      variance of the N10 between good and bad outcome groups existed at 24, 48 and 72
      h post-CA (p<=0.001). Our study is the first application using SOBI detecting
      variance in neural signals like SSEP. N10 latency variance, related with
      neurophysiological dysfunction, increased after hypoxic-ischemic injury. The SOBI
      technique is an efficient method in the identification of peak detection and
      offers a favorable alternative to reveal the neural transmission variation.

PMID- 21878353
TI  - Role of macrophages in early protective immune responses induced by two vaccines
      against foot and mouth disease.
AB  - Foot and Mouth Disease (FMD) is an acute disease of cloven-hoofed species. We
      studied the protection and early immune response induced in the murine model by
      vaccines formulated with inactivated virus and two different adjuvants. The
      presence of IMS12802PR or ISA206VG adjuvants yielded protection against viral
      challenge at early times post vaccination and induced FMDV-specific, but non
      neutralizing, antibody titers. In vivo macrophage depletion in vaccinated mice
      severely decreased the protection levels after virus challenge, indicating a
      central role of this cell population in the response elicited by the vaccines.
      Accordingly, opsonophagocytosis of FITC-labelled virus was augmented in 802-FMDVi
      and 206-FMDVi vaccinated mice. These results demonstrate the ability of the
      studied adjuvants to enhance the protective responses of these inactivated
      vaccines without the increase in seroneutralizing antibodies and the main role of
      opsonization and phagocytosis in the early protective immune responses against
      FMD infection in the murine model.

PMID- 21878354
TI  - Application of kinase bypass strategies to nucleoside antivirals.
AB  - Nucleoside and nucleotide analogs have served as the cornerstones of antiviral
      therapy for many viruses. However, the requirement for intracellular activation
      and side-effects caused by distribution to off-target sites of toxicity still
      limit the efficacy of the current generation of drugs. Kinase bypass strategies,
      where phosphorylated nucleosides are delivered directly into cells, thereby,
      removing the requirement for enzyme catalyzed phosphorylation steps, have already
      changed the face of antiviral therapy in the form of the acyclic nucleoside
      phosphonates, cidofovir, adefovir (given orally as its dipivoxil prodrug) and
      tenofovir (given orally as its disoproxil prodrug), currently used clinically.
      These strategies hold further promise to advance the field of antiviral therapy
      with at least 10 kinase bypass and tissue targeted prodrugs, representing seven
      distinct prodrug classes, currently in clinical trials. This article reviews the
      history of kinase bypass strategies applied to nucleoside antivirals and the
      evolution of different tissue targeted prodrug strategies, highlighting
      clinically relevant examples.

PMID- 21878356
TI  - Involvement of DNA ligase III and ribonuclease H1 in mitochondrial DNA
      replication in cultured human cells.
AB  - Recent evidence suggests that coupled leading and lagging strand DNA synthesis
      operates in mammalian mitochondrial DNA (mtDNA) replication, but the factors
      involved in lagging strand synthesis are largely uncharacterised. We investigated
      the effect of knockdown of the candidate proteins in cultured human cells under
      conditions where mtDNA appears to replicate chiefly via coupled leading and
      lagging strand DNA synthesis to restore the copy number of mtDNA to normal levels
      after transient mtDNA depletion. DNA ligase III knockdown attenuated the recovery
      of mtDNA copy number and appeared to cause single strand nicks in replicating
      mtDNA molecules, suggesting the involvement of DNA ligase III in Okazaki fragment
      ligation in human mitochondria. Knockdown of ribonuclease (RNase) H1 completely
      prevented the mtDNA copy number restoration, and replication intermediates with
      increased single strand nicks were readily observed. On the other hand, knockdown
      of neither flap endonuclease 1 (FEN1) nor DNA2 affected mtDNA replication. These
      findings imply that RNase H1 is indispensable for the progression of mtDNA
      synthesis through removing RNA primers from Okazaki fragments. In the nucleus,
      Okazaki fragments are ligated by DNA ligase I, and the RNase H2 is involved in
      Okazaki fragment processing. This study thus proposes that the mitochondrial
      replication system utilises distinct proteins, DNA ligase III and RNase H1, for
      Okazaki fragment maturation.

PMID- 21878357
TI  - TRAP-1, the mitochondrial Hsp90.
AB  - Protein folding quality control does not occur randomly in cells, but requires
      the action of specialized molecular chaperones compartmentalized in subcellular
      microenvironments and organelles. Fresh experimental evidence has now linked a
      mitochondrial-specific Heat Shock Protein-90 (Hsp90) homolog, Tumor Necrosis
      Factor Receptor-Associated Protein-1 (TRAP-1) to pleiotropic signaling
      circuitries of organelle integrity and cellular homeostasis. TRAP-1-directed
      compartmentalized protein folding is broadly exploited in cancer and
      neurodegenerative diseases, presenting new opportunities for therapeutic
      intervention in humans. This article is part of a Special Issue entitled: Heat
      Shock Protein 90 (Hsp90).

PMID- 21878358
TI  - Radical reversal of vasoactive intestinal peptide (VIP) receptors during early
      lymphopoiesis.
AB  - Successful thymocyte maturation is essential for normal, peripheral T cell
      function. Vasoactive intestinal peptide (VIP) is a neuropeptide which is highly
      expressed in the thymus that has been shown to modulate thymocyte development.
      VIP predominantly binds two G protein coupled receptors, termed vasoactive
      intestinal peptide receptor 1 (VPAC1) and VPAC2, but their expression profiles in
      CD4(-)/CD8(-) (double negative, DN) thymocyte subsets, termed DN1-4, have yet to
      be identified. We hypothesized that a high VPAC1:VPAC2 ratio in the earliest
      thymocyte progenitors (ETP cells) would be reversed during early lymphopoiesis as
      observed in activated, peripheral Th(2) cells, as the thymus is rich in Th(2)
      cytokines. In support of this hypothesis, high VPAC1 mRNA levels decreased 1000
      fold, accompanied with a simultaneous increase in VPAC2 mRNA expression during
      early thymocyte progenitor (ETP/DN1)->DN3 differentiation. Moreover, arrested DN3
      cells derived from an Ikaros null mouse (JE-131 cells) failed to completely
      reverse the VIP receptor ratio compared to wild type DN3 thymocytes.
      Surprisingly, VPAC2(-/-) mice did not show significant changes in relative
      thymocyte subset numbers. These data support the notion that both VPAC1 and VPAC2
      receptors are dynamically regulated by Ikaros, a master transcriptional regulator
      for thymocyte differentiation, during early thymic development. Moreover, high
      VPAC1 mRNA is a novel marker for the ETP population making it enticing to
      speculate that the chemotactic VIP/VPAC1 signaling axis may play a role in
      thymocyte movement. Also, despite the results that VPAC2 deficiency did not
      affect thymic subset numbers, future studies are necessary to determine whether
      downstream T cell phenotypic changes manifest themselves, such as a propensity
      for a Th(1) versus Th(2) polarization.

PMID- 21878359
TI  - On the impact of second generation mating and offspring in multi-generation
      reproductive toxicity studies on classification and labelling of substances in
      Europe.
AB  - The possible impact on classification and labelling decisions of effects observed
      in second generation parental (P1) and offspring (F2) parameters in multi
      generation studies was investigated. This was done for 50 substances classified
      as reproductive toxicants in Europe, for which a multi-generation study was
      available. The P1 and F2 effects were compared to parental (P0) and first
      generation offspring (F1) effects with regard to type of effect as well as
      incidence, magnitude and severity (IMS), at any dose level. For every study with
      unique P1/F2 effects, or differences in IMS, the influence of the P1/F2 findings
      on the classification decision was investigated. Unique P1/F2 generation findings
      did not play a crucial role in the classification decision of any of the 50
      classified substances, except for fenarimol. This substance however provided
      abundant alerts on the basis of its endocrine activity and developmental
      neurotoxicity and would therefore also be expected to be identified as a
      developmental neurotoxicant in an Extended One Generation Reproductive Toxicity
      Study (EOGRTS). These findings, in addition to the increased number of parameters
      analysed, increased statistical power and reduced animal use, provide strong
      further support for replacement of the classical two-generation reproductive
      toxicity study by the EOGRTS in regulatory reproductive toxicity assessment.

PMID- 21878355
TI  - Genetic influence on the working memory circuitry: behavior, structure, function
      and extensions to illness.
AB  - Working memory is a highly heritable complex cognitive trait that is critical for
      a number of higher-level functions. However, the neural substrates of this
      behavioral phenotype are intricate and it is unknown through what precise
      biological mechanism variation in working memory is transmitted. In this review
      we explore different functional and structural components of the working memory
      circuitry, and the degree to which each of them is contributed to by genetic
      factors. Specifically, we consider dopaminergic function, glutamatergic function,
      white matter integrity and gray matter structure all of which provide potential
      mechanisms for the inheritance of working memory deficits. In addition to
      discussing the overall heritability of these measures we also address specific
      genes that may play a role. Each of these heritable components has the potential
      to uniquely contribute to the working memory deficits observed in genetic
      disorders, including 22q deletion syndrome, fragile X syndrome, phenylketonuria
      (PKU), and schizophrenia. By observing the individual contributions of
      disruptions in different components of the working memory circuitry to behavioral
      performance, we highlight the concept that there may be many routes to a working
      memory deficit; even though the same cognitive measure may be a valid
      endophenotype across different disorders, the underlying cause of, and treatment
      for, the deficit may differ. This has implications for our understanding of the
      transmission of working memory deficits in both healthy and disordered
      populations.

PMID- 21878360
TI  - Neurotoxic/neuroprotective activity of haloperidol, risperidone and paliperidone
      in neuroblastoma cells.
AB  - The neurotoxicity of antipsychotic (AP) drugs seems to be linked with
      neurological side effects like extrapyramidal symptoms (EPS). On the other hand,
      neuroprotective effects can mitigate or slow the progressive degenerative
      structural changes in the brain leading to improved outcome of schizophrenia.
      First and second-generation antipsychotics may differ in their neurotoxic and
      neuroprotective properties. The aim of this study was to compare the
      neurotoxic/neuroprotective activity of haloperidol, a first-generation
      antipsychotic, and risperidone, a second-generation one, with paliperidone, a
      relatively new second-generation antipsychotic, in SK-N-SH cells. Haloperidol,
      risperidone and paliperidone (10, 50, 100 MUM) were administered, either alone or
      in combination with dopamine (100 MUM), to human neuroblastoma SK-N-SH. We
      examined the effects of the drugs on cell viability (measured by alamarBlue(r)),
      caspase-3 activity (measured by fluorimetric assay) and cell death (by measuring
      the externalization of phosphatidylserine). Haloperidol significantly decreased
      cell viability and increased caspase-3 activity and cell death. Risperidone and
      paliperidone did not affect cell viability or cell death. Both second-generation
      APs decreased caspase-3 activity, especially paliperidone. In cells treated with
      dopamine in combination with antipsychotics, only paliperidone (10 MUM) induced a
      slight improvement in cell viability. While haloperidol potentiated the dopamine
      induced increase in caspase-3 activity, risperidone and paliperidone reduced this
      effect. The results indicate that haloperidol induces apoptosis, whereas
      risperidone and paliperidone may afford protection against it. Of the APs tested,
      paliperidone always showed the strongest neuroprotective effect. The different
      antipsychotic effects on survival and cell death might be related to differences
      in their capacity to induce EPS.

PMID- 21878361
TI  - Toxic profile of bergamot essential oil on survival and proliferation of SH-SY5Y
      neuroblastoma cells.
AB  - Cosmetic, pharmaceutical, food and confectionary industries make increasing use
      of plant extracts in their products. Despite the widespread use of products
      containing plant extracts, the mechanisms of their effects are not fully
      characterized. Bergamot essential oil (BEO; Citrus bergamia, Risso) is a well
      known plant extract used in aromatherapy and it has analgesic, anxiolytic and
      neuroprotective effects in rodents. To elicit neuroprotection, BEO recruits Akt
      prosurvival pathways. However, Akt stimulates cell proliferation, which may also
      pose risks for health in case of prolonged use. To study the potential effects of
      BEO on survival and proliferation of dividing cells, we selected human SH-SY5Y
      neuroblastoma cells. BEO triggered concentration-dependent mitochondrial
      dysfunction, cytoskeletal reorganization, cell shrinkage, DNA fragmentation and
      both caspase-dependent and independent cell death. Analysis of cleavage products
      of poly-(ADP-ribose) polymerase (PARP) revealed caspase-3 activation, but also
      activation of additional protease families. As result of increased proteolytic
      activity, Akt protein levels decreased in BEO-treated cells. Our data show that
      BEO can be lethal for dividing cells by activating multiple pathways. While this
      may reduce the risk of unwanted cell proliferation after prolonged use, it does
      suggest a cautionary approach to the use of inappropriate dilutions of the oil
      that may cause cell death.

PMID- 21878362
TI  - Screening for in vitro antioxidant properties and fatty acid profiles of five
      Centaurea L. species from Turkey flora.
AB  - Centaurea species are used for the treatment of various ailments in the popular
      medicine in some countries. This study was designed to examine antioxidant
      potentials and fatty acid profiles of five Centaurea species from Turkey flora.
      Antioxidant properties of methanolic extracts from these species were evaluated
      by six different methods: phosphomolybdenum assay, free radical scavenging assay,
      beta-carotene/linoleic acid test system, metal chelating activity, ferric and
      cupric reducing power. Total phenolic and flavonoid concentrations of each
      extract were also determined using the Folin-Ciocalteu reagent and aluminum
      chloride. The results of these assay showed a significant antioxidant capacity in
      all researched extracts. Centaurea cheirolopha extract, with the highest amount
      of total phenolic and flavonoids, showed the highest antioxidant activities in
      all assay, except for metal chelating. Fatty acid profiles of these species were
      examined by GC-FID and 30 fatty acids were identified. Palmitic, linoleic, oleic,
      and linolenic acid were detected as the main components. The results of the study
      indicated that the Centaurea species can be considered as a source of new natural
      antioxidants and unsaturated fatty acids for food, cosmetic and pharmaceutical
      industries.

PMID- 21878363
TI  - The serotonergic system in Parkinson's disease.
AB  - Although the cardinal manifestations of Parkinson's disease (PD) are attributed
      to a decline in dopamine levels in the striatum, a breadth of non-motor features
      and treatment-related complications in which the serotonergic system plays a
      pivotal role are increasingly recognised. Serotonin (5-HT)-mediated
      neurotransmission is altered in PD and the roles of the different 5-HT receptor
      subtypes in disease manifestations have been investigated. The aims of this
      article are to summarise and discuss all published preclinical and clinical
      studies that have investigated the serotonergic system in PD and related animal
      models, in order to recapitulate the state of the current knowledge and to
      identify areas that need further research and understanding.

PMID- 21878364
TI  - Amygdala hyperactivation and prefrontal hypoactivation in subjects with cognitive
      vulnerability to depression.
AB  - The hopelessness theory (HT) of depression is a diathesis-stress theory which
      construes cognitive vulnerability (CV) to depression. Neuroimaging studies
      examining depression have implicated the amygdala as an important potential locus
      of dysfunction in the processing of salient threatening stimuli. However, little
      is known about neural activation in the brain of subjects with CV to depression.
      Medication-free major depressive disorder (MDD) subjects (N=29), never depressed
      subjects with CV (N=26), and demographically matched never depressed healthy
      control (HC) subjects (N=31) were scanned using functional magnetic resonance
      imaging (fMRI) while performing an emotional matching task. The MDD subjects
      showed elevated left amygdala responses and reduced left dorsolateral prefrontal
      cortex (dlPFC) activation levels relative to HC subjects. Similarly, CV subjects
      had greater activity in the amygdala bilaterally and lesser activation in the
      dlPFC bilaterally, relative to HC subjects. The present findings raise the
      possibility that cognitive vulnerability to depression might be characterized by
      hypoactivation of the prefrontal cortex and hyperactivation of the amygdala in
      response to emotional stimuli; our observations might provide a potential
      interpretation to explain the abnormalities in neural networks mediating
      cognitive modulation of emotions in individuals with cognitive vulnerability to
      depression.

PMID- 21878365
TI  - 2,3-Diaryl-2H-1-benzopyran derivatives interfere with classical and non-classical
      estrogen receptor signaling pathways, inhibit Akt activation and induce apoptosis
      in human endometrial cancer cells.
AB  - OBJECTIVES: The present study was undertaken to explore the mechanism of anti
      proliferative action of benzopyran compound D1 (2-[piperidinoethoxyphenyl]-3
      phenyl-2H-benzopyran) and its hydroxy-(D2) and methoxy-(D3) derivatives in
      Ishikawa and human primary endometrial adenocarcinoma cells. METHODS:
      Transcriptional activation assays were performed using luciferase reporter system
      and cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5
      diphenyltetrazolium bromide (MTT). The stage of cell cycle was determined by flow
      cytometry and real time analysis of cyclinE1 and cdc2 genes. The apoptotic
      effects were measured by AnnexinV/PI staining and TUNEL. The expression of PCNA,
      cyclinD1, pAkt, XIAP, cleaved caspase-9, -3, PARP, Bax and Bcl2 were determined
      by immunoblotting. The caspase-3 activity and mitochondrial membrane potential
      were measured by colorimetric assay. RESULTS: All three compounds inhibited E(2)
      induced ERE- and AP-1-mediated transactivation and proliferation in endometrial
      adenocarcinoma cells dose-dependently. Compound D1 caused the arrest of cells in
      the G(2) phase while D2 and D3 caused arrest in G(1) phase of the cell cycle. All
      compounds interfered with Akt activation, decreased XIAP expression leading to an
      increased cleavage of caspase-9, -3, PARP, increased Bax/Bcl2 ratio and caspase-3
      activity. CONCLUSION: Findings suggest that benzopyran derivatives inhibit
      cellular proliferation via modulating ER-dependent classical and non-classical
      signaling mechanisms, interfere with Akt activation and induce apoptosis via
      intrinsic pathway in endometrial adenocarcinoma cells.

PMID- 21878366
TI  - Privileged coupling between Ca(2+) entry through plasma membrane store-operated
      Ca(2+) channels and the endoplasmic reticulum Ca(2+) pump.
AB  - The sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) is the third element of
      capacitative calcium entry. It colocalizes with STIM1 and Orai1 at puncta, where
      couples plasma membrane store-operated Ca(2+) channels (SOC) to Ca(2+) pumping
      into the ER. The efficiency of this calcium entry-calcium refilling (CECR)
      coupling is comparable to the classic excitation-response transduction
      mechanisms. This allows efficient filling of the endoplasmic reticulum (ER) with
      the Ca(2+) entering through SOC channels with little progression of the Ca(2+)
      wave towards the cell core. CECR coupling is very sensitive to changes in
      stoichiometry among STIM, Orai and SERCA, with excess Orai antagonizing ER
      refilling. ER takes up most of the calcium load that enters through SOC, whereas
      mitochondria take up a very small fraction. This difference is due to the spatial
      positioning with regard to SOC, the amplitude of the high Ca(2+) microdomains,
      and the differences in the Ca(2+) affinity of the uptake mechanisms.

PMID- 21878367
TI  - Redox-regulating role of insulin: the essence of insulin effect.
AB  - It is well-known that insulin acts as an important hormone, controlling energy
      metabolism, cellular proliferation and biosynthesis of functional molecules to
      maintain a biological homeostasis. Over the past few years, intensive insulin
      therapy has been believed to be benefit for the outcome of diabetic patients, in
      which the suppression of oxidative stress plays a role. Moreover, insulin is
      accepted as a key component of glucose-insulin-potassium, a treatment which has
      been believed to exert significant cardiovascular protective effect via the
      reduction of oxidative stress. Furthermore, accumulating evidence has suggested
      that insulin exerts important redox-regulating actions in various insulin
      sensitive target organs, implying the systematic antioxidative role of insulin as
      a hormone. It is time for us to revisit insulin effects, through summarizing and
      evaluating the novel functions of insulin and their mechanisms. This review
      focuses on the antioxidative effect of insulin and highlights insulin-induced
      regulation of various antioxidant enzymes via insulin signaling pathways and the
      cross talk between key transcription factors, including nuclear factor erythroid
      2-related factor 2 (Nrf2) and nuclear factor kappaB (NF-kappaB) which are
      responsible for the transcription of antioxidant enzymes, leading to reduced
      generation of reactive oxygen species (ROS) and the enhancement of the
      elimination of ROS.

PMID- 21878368
TI  - A conserved surface on the ligand binding domain of nuclear receptors for
      allosteric control.
AB  - Nuclear receptors (NRs) form a large superfamily of transcription factors that
      participate in virtually every key biological process. They control development,
      fertility, gametogenesis and are misregulated in many cancers. Their enormous
      functional plasticity as transcription factors relates in part to NR-mediated
      interactions with hundreds of coregulatory proteins upon ligand (e.g., hormone)
      binding to their ligand binding domains (LBD), or following covalent
      modification. Some coregulator association relates to the distinct residues that
      shape a coactivator binding pocket termed AF-2, a surface groove that primarily
      determines the preference and specificity of protein-protein interactions.
      However, the highly conserved AF-2 pocket in the NR superfamily appears to be
      insufficient to account for NR subtype specificity leading to fine
      transcriptional modulation in certain settings. Additional protein-protein
      interaction surfaces, most notably on their LBD, may contribute to modulating NR
      function. NR coregulators and chaperones, normally much larger than the NR
      itself, may also bind to such interfaces. In the case of the androgen receptor
      (AR) LBD surface, structural and functional data highlighted the presence of
      another site named BF-3, which lies at a distinct but topographically adjacent
      surface to AF-2. AR BF-3 is a hot spot for mutations involved in prostate cancer
      and androgen insensitivity syndromes, and some FDA-approved drugs bind at this
      site. Structural studies suggested an allosteric relationship between AF-2 and BF
      3, as occupancy of the latter affected coactivator recruitment to AF-2.
      Physiological relevant partners of AR BF-3 have not been described as yet. The
      newly discovered site is highly conserved among the steroid receptors subclass,
      but is also present in other NRs. Several missense mutations in the BF-3 regions
      of these human NRs are implicated in pathology and affect their function in
      vitro. The fact that AR BF-3 pocket is a druggable site evidences its
      pharmacological potential. Compounds that may affect allosterically NR function
      by binding to BF-3 open promising avenues to develop type-specific NR modulators.

PMID- 21878369
TI  - The role of thioredoxin in the regulation of cellular processes by S
      nitrosylation.
AB  - BACKGROUND: S-nitrosylation (or S-nitrosation) by Nitric Oxide (NO), i.e., the
      covalent attachment of a NO group to a cysteine thiol and formation of S
      nitrosothiols (R-S-N=O or RSNO), has emerged as an important feature of NO
      biology and pathobiology. Many NO-related biological functions have been directly
      associated with the S-nitrosothiols and a considerable number of S-nitrosylated
      proteins have been identified which can positively or negatively regulate various
      cellular processes including signaling and metabolic pathways. SCOPE OF THE
      REVIEW: Taking account of the recent progress in the field of research, this
      review focuses on the regulation of cellular processes by S-nitrosylation and Trx
      mediated cellular homeostasis of S-nitrosothiols. MAJOR CONCLUSIONS: Thioredoxin
      (Trx) system in mammalian cells utilizes thiol and selenol groups to maintain a
      reducing intracellular environment to combat oxidative/nitrosative stress.
      Reduced glutathione (GSH) and Trx system perform the major role in
      denitrosylation of S-nitrosylated proteins. However, under certain conditions,
      oxidized form of mammalian Trx can be S-nitrosylated and then it can trans-S
      nitrosylate target proteins, such as caspase 3. GENERAL SIGNIFICANCE:
      Investigations on the role of thioredoxin system in relation to biologically
      relevant RSNOs, their functions, and the mechanisms of S-denitrosylation
      facilitate the development of drugs and therapies. This article is part of a
      Special Issue entitled Regulation of Cellular Processes.

PMID- 21878370
TI  - Form of dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1A
      nonphosphorylated at tyrosine 145 and 147 is enriched in the nuclei of astroglial
      cells, adult hippocampal progenitors, and some cholinergic axon terminals.
AB  - Compelling lines of evidence indicate that overexpression of dual-specificity
      tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A) in subjects with
      trisomy 21 (Down syndrome[DS]) contributes to the abnormal structure and function
      of the DS brain. In the present study, we used a novel, phospho-dependent
      antibody recognizing DYRK1A only with nonphosphorylated tyrosine 145 and 147
      (DYRK1A Tyr-145/147P(-)), to investigate the expression pattern of this DYRK1A
      species in trisomic and disomic human and mouse brains. Immunoblotting and
      dephosphorylation experiments demonstrated higher levels of DYRK1A Tyr-145/147P(
      ) in postnatal trisomic brains in comparison with controls (by ~40%) than those
      of the DYRK1A visualized by three other N- and C-terminally directed antibodies
      to DYRK1A. By immunofluorescence, the immunoreactivity to DYRK1A Tyr-145/147P(-)
      was the strongest in the nuclei of astroglial cells, which contrasted with the
      predominantly neuronal localization of DYRK1A visualized by the three other
      antibodies to DYRK1A we used. In addition, DYRK1A Tyr-145/147P(-) was enriched in
      the nuclei of neuronal progenitors and newly born neurons in the adult
      hippocampal proliferative zone and also occurred in some cholinergic axonal
      terminals. Our data show a distinctive expression pattern of DYRK1A forms
      nonphosphorylated at Tyr-145 and Tyr-147 in the brain tissue and suggest that DS
      subjects may exhibit not only upregulation of total DYRK1A, but also more subtle
      differences in phosphorylation levels of this kinase in comparison with control
      individuals.

PMID- 21878371
TI  - Effect of unilateral subthalamic deep brain stimulation on rat digestive motor
      activity.
AB  - A significant proportion of patients with Parkinson's disease suffers from
      digestive symptoms. Bilateral deep brain stimulation of the subthalamic nucleus
      has become a reliable therapeutic option for parkinsonian patients, but its
      effects on digestive motility remain poorly investigated. The aim of our study
      was to assess whether subthalamic stimulation could induce changes in gastric,
      colonic, and rectal motility and modulate brain centers involved in gut motility.
      METHODS: In anesthetized rats, unilateral subthalamic nucleus stereotactic
      implantation was performed while intra-gastric, -colonic, and -rectal pressures
      were recorded during the ON and OFF periods of the stimulation. c-Fos protein
      expression was quantified by immunostaining in the nucleus of the solitary tract,
      the dorsal motor nucleus of the vagus nerve, the locus coeruleus, and the
      Barrington's nucleus. RESULTS: Compared to baseline, sham stimulation did not
      change phasic gastric, colonic or rectal motor activity. Unilateral subthalamic
      stimulation increased colonic phasic motility (P<0.05) compared to baseline and
      the OFF period with no change in gastric and rectal motility. Pre-treatment with
      atropine, or specific D1 and D2 receptors antagonists prevented the rise in
      colonic motor activity. An increase in c-Fos protein-positive cells within all
      the studied nuclei was observed in the stimulated group compared to the sham
      group. CONCLUSIONS: Unilateral subthalamic stimulation impacts on gut motility in
      anesthetized rats with a significant increase in colonic motility probably via
      the modulation of several brain centers. These findings warrant further
      confirmation in parkinsonian rat models before being transposed to clinical
      conditions.

PMID- 21878372
TI  - The temporal pattern of postnatal neurogenesis found in the neocortex of the
      Gottingen minipig brain.
AB  - The Gottingen minipig (G-mini) is increasingly used as a non-primate model for
      human neurological diseases. We applied design-based stereology on five groups of
      G-minis aged 1 day, 14 days, 30 days, 100 days, and 2 years or older to estimate
      the pattern of postnatal neuron number development in the neocortex. Two time
      periods for the postnatal increase of neocortical neuron number were observed
      from the time of birth to day 14 (P=0.013) and from day 30 to day 100 (P<0.001).
      No significant change in neuron number was found from day 14 to 30 (P=0.58) and
      day 100 onward (P=0.39). The average estimated total number of neurons in the
      neocortex was 236, 274, 264, 338, and 353 million, respectively. Since
      neurogenesis and neuronal migration in the human neocortex are generally accepted
      to be complete before term, the application of G-mini as human disease models may
      be inappropriate before day 100. However, G-mini may serve as a valuable model
      for the studies of ongoing neurogenesis in the living brain.

PMID- 21878373
TI  - Hydrolytic fate of deoxynivalenol-3-glucoside during digestion.
AB  - Deoxynivalenol-3-beta-D-glucoside (D3G), a plant phase II metabolite of the
      Fusarium mycotoxin deoxynivalenol (DON), occurs in naturally contaminated wheat,
      maize, oat, barley and products thereof. Although considered as a detoxification
      product in plants, the toxicity of this substance in mammals is currently
      unknown. A major concern is the possible hydrolysis of the D3G conjugate back to
      its toxic precursor mycotoxin DON during mammalian digestion. We used in vitro
      model systems to investigate the stability of D3G to acidic conditions,
      hydrolytic enzymes and intestinal bacteria, mimicking different stages of
      digestion. D3G was found resistant to 0.2 M hydrochloric acid for at least 24 h
      at 37  degrees C, suggesting that it will not be hydrolyzed in the stomach of
      mammals. While human cytosolic beta-glucosidase also had no effect, fungal
      cellulase and cellobiase preparations could cleave a significant portion of D3G.
      Most importantly, several lactic acid bacteria such as Enterococcus durans,
      Enterococcus mundtii or Lactobacillus plantarum showed a high capability to
      hydrolyze D3G. Taken together these data indicate that D3G is of toxicological
      relevance and should be regarded as a masked mycotoxin.

PMID- 21878374
TI  - 32P-HPLC analysis of N1-(2-carboxy-2-hydroxyethyl)deoxyadenosine: a DNA adduct of
      the acrylamide-derived epoxide glycidamide.
AB  - Acrylamide (AA) is produced in many types of food products cooked or processed at
      high temperature. AA is metabolized to the epoxide glycidamide (GA), which can
      bind to deoxyguanosine and deoxyadenosine in DNA. The GA-derived N7-guanine and
      N3-adenine adducts are the only products which so far have been analysed in vivo.
      Because of previous excellent experience from analysis of adducts to N1-adenine,
      the aim of our study was to investigate if the N1-adenine adduct of GA could be
      used as a biomarker of AA exposure. A 32P-postlabelling method was developed and
      tested (a) on DNA modified in vitro with GA, (b) on cells treated with GA and (c)
      on liver DNA from mice treated with AA. The N1-adenine adduct of GA (analysed
      after conversion to N6-GA-deoxyadenosine-5'-monophosphate) was easily detected in
      DNA reacted with GA and in DNA from cells exposed to GA, but not in DNA from mice
      treated with AA. The reason for this is currently not clearly understood, but
      some of the possible contributing factors are discussed. The application of the
      method in other experimental conditions should be further pursued in order to
      solve this matter.

PMID- 21878375
TI  - Dimethyl sulfoxide (DMSO) attenuates the inflammatory response in the in vitro
      intestinal Caco-2 cell model.
AB  - This study aimed to investigate dose effects of dimethyl sulfoxide (DMSO) (0.05
      1%) on the intestinal inflammatory response in confluent- and differentiated-Caco
      2 cells stimulated with interleukin (IL)-1beta or a pro-inflammatory cocktail for
      24 h. Cyclooxygenase-2 (COX-2) activity was assayed by incubating inflamed cells
      with arachidonic acid and then measuring prostaglandin-E(2) (PGE(2)) produced.
      Soluble mediators (IL-8, IL-6, macrophage chemoattractant protein-1 (MCP-1), and
      COX-2-derived PGE(2)) were quantified by enzyme immunoassays and mRNA expression
      of 33 proteins by high throughput TaqMan Low Density Array. Data showed that DMSO
      decreased induced IL-6 and MCP-1 secretions in a dose-dependent manner (P<0.05),
      but not IL-8; these effects were cell development- and stimulus- independent.
      Moreover, in IL-1beta-stimulated confluent-cells, DMSO dose-dependently reduced
      COX-2-derived PGE(2) (P<0.05). DMSO at 0.5% decreased significantly mRNA levels
      of 14 proteins involved in the inflammatory response (including IL-6, IL-1alpha,
      IL-1beta, and COX-2). Thus, DMSO at low concentrations (0.1-0.5%) exhibits anti
      inflammatory properties in the in vitro intestinal Caco-2 cell model. This point
      is important to be taken into account when assessing anti-inflammatory properties
      of bioactive compounds requiring DMSO as vehicle, such as phenolic compounds, in
      order to avoid miss-interpretation of the results.

PMID- 21878376
TI  - Preparation of a solid-in-oil nanosuspension containing L-ascorbic acid as a
      novel long-term stable topical formulation.
AB  - L-Ascorbic acid (AA, vitamin C) easily decomposes into inactive compounds in
      aqueous solutions and this has limited its topical use. This work reports the
      preparation of a solid-in-oil nanosuspension (SONS) containing AA and validation
      of its basic storage stability. Although AA itself is water-soluble, it can
      readily be nanosuspended in squalane via complex formation involving a
      combination of sucrose erucate (i.e. lipophilic surfactant) and sucrose
      monolaureate (i.e. hydrophilic surfactant) to yield SONS with a very low moisture
      content (<500 ppm). To extract encapsulated AA, a lipase-based enzymatic
      degradation technique was used to degrade a formulation phase making it easier
      for AA to distribute into an extraction solution. Our results demonstrate that
      almost all the encapsulated AA (95.3%) was readily extracted from the SONS upon
      addition of medium-chain triglyceride, which offers the possibility of degrading
      the formulation phase using lipase. Finally, its storage stability study was
      investigated at 25 degrees C over 90 days under protection from light. An aqueous
      solution containing AA was used as a control. Compared with the control, the SONS
      markedly increased the stability of AA due to its low moisture content and, thus,
      the potential usefulness SONSs as a novel long-term stable topical formulation of
      AA has been proved.

PMID- 21878377
TI  - Guest molecular size-dependent inclusion complexation of parabens with cholic
      acid by cogrinding.
AB  - Effects of p-hydroxybenzoate (paraben) ester chain length on the stoichiometry
      and structure of grinding-induced inclusion complexes with cholic acid (CA) were
      investigated. Physicochemical properties of the ground mixture were evaluated by
      powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), Fourier
      transform infrared (FT-IR) spectroscopy, and solid-state nuclear magnetic
      resonance (NMR) measurements. Ethyl-, n-propyl-, and isopropyl-parabens formed
      equimolar inclusion complexes with CA, and the complex structures were of the
      beta-trans bilayer type. In contrast, the stoichiometry of the CA-paraben complex
      was 2:1, and the structure was of the alpha-gauche bilayer type when
      isobutylparaben was used as a guest molecule. Although the stoichiometries and
      structures of the complexes differed, solid-state NMR showed that the molecular
      states of parabens in the complexes were similar and independent of the ester
      chain length. Complexes between CA and parabens with longer substituent groups (C
      >4) were not observed. Steric effects induced by increasing the guest size are
      likely to influence the overall structure of inclusion complexes. Mechanical
      forces and thermal activation by grinding were important factors in the mechanism
      of CA-paraben complex formation.

PMID- 21878378
TI  - Enhanced bioavailability after oral and pulmonary administration of baicalein
      nanocrystal.
AB  - The aim of the study was to investigate the potential of oral and pulmonary
      nanocrystal to enhance the bioavailability of baicalein, a bioactive flavonoid
      isolated from the root of Scutellaria baicalensis Georgi. So far, the nano-sized
      delivery system of baicalein and its pulmonary delivery have received no
      exploration. In the present investigation, the baicalein nanocrystal was prepared
      by anti-solvent recrystallization followed by high pressure homogenization. In
      vitro characterization was performed including particle size and distribution,
      Zeta potential, dissolution, scanning electron microscopy, differential scanning
      calorimetry and X-ray powder diffractometry. It was indicated that no crystalline
      change was observed after nanocrystal preparation. The baicalein nanocrystal
      containing only trace of stabilizer exhibited a significantly enhanced
      dissolution of baicalein. In vivo test was also carried out in rats and
      pharmacokinetic parameters of the baicalein crystal and the baicalein nanocrystal
      after gavage and pulmonary administration were compared, based on the
      simultaneous determination of baicalein and baicalin by high performance liquid
      chromatography. The mean relative bioavailability of oral baicalein nanocrystal
      was 1.67-fold that of oral baicalein crystal. The pulmonary baicalein nanocrystal
      had rapid and extensive absorption and had almost identical pharmacokinetic
      parameters to intravenous baicalein injection.

PMID- 21878380
TI  - The effect of Compound Danshen Dripping Pills, a Chinese herb medicine, on the
      pharmacokinetics and pharmacodynamics of warfarin in rats.
AB  - AIM OF THE STUDY: Significant pharmacokinetic/pharmacodynamic (PK/PD)
      interactions between various herbal products and warfarin have recently been
      reported. The present study was conducted to determine whether Compound Danshen
      Dripping Pills (CDDP), a Chinese herb medicine used for the treatment of
      cardiovascular diseases, interacts with warfarin when administered concomitantly.
      MATERIALS AND METHODS: Each day for 7 days two groups of rats were treated orally
      with CDDP (50mg/kg and 250 mg/kg, twice daily), and the control group received
      similar treatment with appropriate volumes of water only. Sixty minutes after the
      final daily administration of CDDP or water, an aqueous solution of warfarin
      (0.2mg/mL) was given to each rat at a dose of 1.0mg/kg, and blood samples were
      collected at 0, 0.5, 1, 2, 4, 8, 12, 24, 36, and 48 h after warfarin-treatment.
      The concentration of warfarin in blood plasma was determined by high performance
      liquid chromatography (HPLC). Prothrombin time (PT) in blood plasma was measured
      using thromboplastin reagent. RESULTS: Excellent linearity was found between 0.05
      and 10 MUg/mL with a lower limit of quantitation (LLOQ) of 0.05 ng/mL (r>0.999);
      moreover, all the validation data including accuracy and precision (intra- and
      inter-day), were within the required limits. No significant differences were
      found in PT(max) and AUC(PT0-infinity) between the two CDDP-treated groups and
      the control. Besides, there was little alteration in any of the pharmacokinetic
      parameters of warfarin between the two CDDP-treated groups and the control.
      CONCLUSION: The concomitant application of CDDP and warfarin did not give rise to
      significant effect on the pharmacodynamics of warfarin, and practically no effect
      on its pharmacokinetics. It was speculated that the PK/PD interactions between
      CDDP and warfarin was likely to be negligible as long as the patients took CDDP
      at a normal dose.

PMID- 21878379
TI  - The relationship between MOC reflex and masked threshold.
AB  - Otoacoustic emission (OAE) amplitude can be reduced by acoustic stimulation. This
      effect is produced by the medial olivocochlear (MOC) reflex. Past studies have
      shown that the MOC reflex is related to listening in noise and attention. In the
      present study, the relationship between strength of the contralateral MOC reflex
      and masked threshold was investigated in 19 adults. Detection thresholds were
      determined for 1000-Hz, 300-ms tone presented simultaneously with one repetition
      of a 300-ms masker in an ongoing train of masker bursts. Three masking conditions
      were tested: 1) broadband noise 2) a fixed-frequency 4-tone complex masker and 3)
      a random-frequency 4-tone complex masker. Broadband noise was expected to produce
      energetic masking and the tonal maskers were expected to produce informational
      masking in some listeners. DPOAEs were recorded at fine frequency intervals from
      500 to 4000 Hz, with and without contralateral acoustic stimulation. MOC reflex
      strength was estimated as a reduction in baseline level and a shift in frequency
      of DPOAE fine-structure maxima near 1000-Hz. MOC reflex and psychophysical
      testing were completed in separate sessions. Individuals with poorer thresholds
      in broadband noise and in random-frequency maskers were found to have stronger
      MOC reflexes.

PMID- 21878381
TI  - Anti-inflammatory and antinociceptive effects of the stem bark of Byrsonima
      intermedia A. Juss.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Byrsonima intermedia A. Juss. is popularly known
      as "murici pequeno" and is native to the Brazilian Cerrado. This species has been
      used as an antimicrobial, anti-hemorrhagic, anti-diarrheal and anti-inflammatory.
      Nevertheless, scientific information regarding Byrsonima intermedia is limited;
      there are no reports related to its possible anti inflammatory and
      antinociceptive effects. This study employed in vivo inflammatory and nociceptive
      models to evaluate the scientific basis for the traditional use of Byrsonima
      intermedia. MATERIALS AND METHODS: Carrageenan-induced paw edema, peritonitis and
      fibrovascular tissue growth induced by s.c. cotton pellet implantation tests were
      used to investigate the anti-inflammatory activity of Byrsonima intermedia
      aqueous extract (BiAE) in rats. Mechanical nociceptive paw, formalin and hot
      plate tests were used to evaluate the antinociceptive activity in mice. High
      performance liquid chromatography (HPLC), phytochemistry screening and
      determination of total phenolics and flavonoids were used to determine the
      chemical profile of the BiAE. RESULTS: BiAE at test doses of 30-300 mg/kg p.o.
      clearly demonstrated anti-inflammatory effects by reduced carrageenan-induced paw
      edema, by inhibited leukocyte recruitment into the peritoneal cavity and, in the
      model of chronic inflammation, by using the cotton pellet-induced fibrovascular
      tissue growth in rats. The extracts at test doses of 30-300 mg/kg p.o. clearly
      demonstrated antinociceptive activity in all tests. Administration of the opioid
      receptor antagonist naloxone completely inhibited the antinociceptive effect
      induced by BiAE (100 mg/kg). CONCLUSION: BiAE markedly exhibits anti-inflammatory
      action in rats and antinociceptive activity in mice. Thus, it may be useful in
      the treatment of inflammatory hyperalgesic disorders, which supports previous
      claims of its traditional use.

PMID- 21878382
TI  - Ginkgolide B reduces neuronal cell apoptosis in the hemorrhagic rat brain:
      possible involvement of Toll-like receptor 4/nuclear factor-kappa B pathway.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgolide B (GB) is one of the ginkgolides that
      have been isolated from leaves and root bark of the Chinese tree Ginkgo biloba L.
      (Ginkgoaceae), and is a specific and potent antagonist of platelet activating
      factor. There is a large body of data showing that GB possesses a markedly
      neuroprotective property against ischemia-induced impairment in vivo and in
      vitro. Recently it has been found that GB can inhibit the inflammation in the rat
      brain tissues with ischemia/reperfusion injury and in the astrocytes treated with
      lipopolysaccharide, as well as protect neurons against beta-amyloid 25-35 and
      ischemia-induced apoptosis. However, there have been few reports on the influence
      of GB on intracerebral hemorrhage (ICH). This study was to investigate the
      effects of intraperitoneal GB on neuronal cell apoptosis, inflammatory cytokines
      and Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-kappaB) pathway after
      ICH. MATERIALS AND METHODS: Wistar rats obtained an intraperitoneal injection of
      5, 10 and 20mg/kg GB after ICH once a day till day 5. Rats were sacrificed by
      decapitation at hour 2, 6 and 12, as well as day 1, 2, 3 and 5 after ICH. Gene
      expressions of TLR-4 and NF-kappaB, concentrations of tumor necrosis factor-alpha
      (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) as well as
      number of apoptotic neuronal cells in hemorrhagic rat brain tissues were
      determined. RESULTS: The administration of 10 and 20mg/kg GB could significantly
      suppress gene expressions of TLR-4 and NF-kappaB, lessen concentrations of TNF
      alpha, IL-1beta and IL-6 as well as reduce number of apoptotic neuronal cells in
      hemorrhagic rat brain tissues by Least-significant Difference test (P<0.05), but
      the administration of 5mg/kg GB not (P>0.05). However, a clear concentration
      response relationship was not found. CONCLUSIONS: GB may inhibit TLR4/NF-kappaB
      dependent inflammatory responses, and furthermore lessen neuronal cell apoptosis
      after ICH, which may support the use of G. biloba extracts for the treatment of
      ICH.

PMID- 21878383
TI  - The synergistic anti-inflammatory effect of the combination of sodium ferulate
      and oxymatrine and its modulation on inflammation-associated mediators in RAW
      264.7 cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The combination of Radix Angelicae sinensis
      (Oliv.) Diels and Radix Sophora flavescens Ait. was extensively used in
      traditional Chinese medicine to treat inflammatory diseases, such as acne, heart
      disease, and hepatitis. Sodium ferulate (SF) and oxymatrine (OMT) were effective
      component of Radix Angelicae sinensis (Oliv.) Diels and Radix Sophora flavescens
      Ait., respectively. AIM OF THE STUDY: In this study, we investigated the
      synergistic anti-inflammatory effect of the combination of SF and OMT, and its
      modulation on inflammation-associated mediators in RAW 264.7 cells. MATERIALS AND
      METHODS: In vivo, the anti-inflammatory effects of the combination of SF and OMT
      were evaluated with the xylene-induced mouse ear edema model and the carrageenan
      induced rat paw edema model. In vitro, chemokines and cytokines mRNA expressions
      in lipopolysaccharide (LPS)-activated RAW 264.7 cells were determined by real
      time PCR (RT-PCR) microarray analysis. The levels of interleukin-11 (IL-11), C
      reactive protein (CRP) and interferon-gamma (INF-gamma) in the supernatant of LPS
      stimulated RAW 264.7 cells were measured by enzyme-linked immune-sorbent assay
      (ELISA). RESULTS: The combination of SF and OMT could significantly inhibit the
      edema in the xylene-induced mouse ear edema and carrageenan-induced rat paw
      edema, but no effect was found when each drug was used alone according to above
      doses. The combination exhibited a better effect in down-regulating mRNA
      expressions of inflammation-associated mediators in LPS-stimulated RAW 264.7
      cells than SF or OMT alone. The ELISA results showed that the combination
      synergistically inhibited LPS-induced IL-11, CRP and INF-gamma production in a
      dose-dependent manner. CONCLUSION: The combination of SF and OMT showed
      synergistic anti-inflammatory effect, and the activity was probably related to
      its modulation on inflammation-associated mediators, especially IL-11, CRP and
      INF-gamma.

PMID- 21878384
TI  - Reproductive toxicity of Rhizoma Sparganii (Sparganium stoloniferum Buch.-Ham.)
      in mice: mechanisms of anti-angiogenesis and anti-estrogen pharmacologic
      activities.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Indications and preliminary studies of Rhizoma
      Sparganii (RS) suggest its pharmacological mechanism is involved with
      endocrine/angiogenesis functions. We therefore studied its potential toxicity on
      reproduction in mice. MATERIALS AND METHODS: Reproductive toxicity of 100, 200
      and 400 mg/kg RS extract were studied in pregnant ICR mice and its offspring. The
      embryos' fibroblast growth factor-1 (FGF-1), vascular endothelial growth factor
      (VEGF) and estrogen receptor-alpha (ER-alpha) were evaluated as targets of
      endocrine/angiogenesis by immunohistochemical test. RESULTS: The offspring of
      treated mice (100, 200 and 400 mg/kg RS extract) during their pregnancy had
      various pathological conditions, suggesting an abnormal FGF signaling phenomenon
      during pregnancy. Embryos from the 400 mg/kg group had significantly depressed
      levels of FGF-1 (P < 0.01) and VEGF (P < 0.05) expression levels as compared to
      controls by immunohistochemical test. Dysplasia in the heart (12.9%),
      craniofacial region (18.3%) and vertebrae (32.5%) presented in embryos of the 400
      mg/kg group. Furthermore, the ER-alpha expression was inversely proportional to
      FGF-1 levels in the same embryo (P < 0.01). CONCLUSIONS: These results implicate
      a FGF signaling abnormality in vivo and indicate that RS has anti-angiogenesis
      and anti-estrogen toxicity effects in pregnant rodents.

PMID- 21878385
TI  - Can we jog our way to a younger-looking immune system?

PMID- 21878386
TI  - Toxicological evaluation of ammonium perfluorobutyrate in rats: twenty-eight-day
      and ninety-day oral gavage studies.
AB  - Sequential 28-day and 90-day oral toxicity studies were performed in male and
      female rats with ammonium perfluorobutyrate (NH(4)(+)PFBA) at doses up to 150 and
      30mg/kg-d, respectively. Ammonium perfluorooctanoate was used as a comparator at
      a dose of 30mg/kg-d in the 28-day study. Female rats were unaffected by
      NH(4)(+)PFBA. Effects in males included: increased liver weight, slight to
      minimal hepatocellular hypertrophy; decreased serum total cholesterol; and
      reduced serum thyroxin with no change in serum thyrotropin. During recovery,
      liver weight, histological, and cholesterol effects were resolved. Results of RT
      qPCR were consistent with increased transcriptional expression of the xenosensor
      nuclear receptors PPARalpha and CAR as well as the thyroid receptor, and
      decreased expression of Cyp1A1 (Ah receptor-regulated). No observable adverse
      effect levels (NOAELs) were 6 and >150mg/kg-d for male and female rats in the 28
      day study and 6 and >30mg/kg-d in the 90-dat study, respectively.

PMID- 21878388
TI  - Drug release control and system understanding of sucrose esters matrix tablets by
      artificial neural networks.
AB  - Artificial neural networks (ANNs) were applied for system understanding and
      prediction of drug release properties from direct compacted matrix tablets using
      sucrose esters (SEs) as matrix-forming agents for controlled release of a highly
      water soluble drug, metoprolol tartrate. Complexity of the system was presented
      through the effects of SE concentration and tablet porosity at various
      hydrophilic-lipophilic balance (HLB) values of SEs ranging from 0 to 16. Both
      effects contributed to release behaviors especially in the system containing
      hydrophilic SEs where swelling phenomena occurred. A self-organizing map neural
      network (SOM) was applied for visualizing interrelation among the variables and
      multilayer perceptron neural networks (MLPs) were employed to generalize the
      system and predict the drug release properties based on HLB value and
      concentration of SEs and tablet properties, i.e., tablet porosity, volume and
      tensile strength. Accurate prediction was obtained after systematically
      optimizing network performance based on learning algorithm of MLP. Drug release
      was mainly attributed to the effects of SEs, tablet volume and tensile strength
      in multi-dimensional interrelation whereas tablet porosity gave a small impact.
      Ability of system generalization and accurate prediction of the drug release
      properties proves the validity of SOM and MLPs for the formulation modeling of
      direct compacted matrix tablets containing controlled release agents of different
      material properties.

PMID- 21878387
TI  - Multicolour interphase cytogenetics: 24 chromosome probes, 6 colours, 4 layers.
AB  - From the late 1980s onwards, the use of DNA probes to visualise sequences on
      individual chromosomes (fluorescent in-situ hybridisation - FISH) revolutionised
      the study of cytogenetics. Following single colour experiments, more
      fluorochromes were added, culminating in a 24 colour assay that could distinguish
      all human chromosomes. Interphase cytogenetics (the detection of chromosome copy
      number in interphase nuclei) soon followed, however 24 colour experiments are
      hampered for this application as mixing fluorochromes to produce secondary
      colours produces images that are not easily distinguishable from overlapping
      signals. This study reports the development and use of a novel protocol, new fast
      hybridising FISH probes, and a bespoke image capture system for the assessment of
      chromosome copy number in interphase nuclei. The multicolour probe sets can be
      used individually or in sequential hybridisation layers to assess ploidy of all
      24 human chromosomes in the same nucleus. Applications of this technique are in
      the investigation of chromosome copy number and the assessment of nuclear
      organisation for a range of different cell types including human sperm, cancer
      cells and preimplantation embryos.

PMID- 21878389
TI  - Desensitization of nicotinic acetylcholine receptors in central nervous system
      neurons of the stick insect (Carausius morosus) by imidacloprid and sulfoximine
      insecticides.
AB  - Imidacloprid, sulfoxaflor and two experimental sulfoximine insecticides caused
      generally depressive symptoms in stick insects, characterized by stillness and
      weakness, while also variably inducing postural changes such as persistent
      ovipositor opening, leg flexion or extension and abdomen bending that could
      indicate excitation of certain neural circuits. We examined the same compounds on
      nicotinic acetylcholine receptors in stick insect neurons, which have previously
      been shown to desensitize in the presence of ACh. Brief U-tube application of 10(
      4) M solutions of insecticides for 1 s evoked currents that were much smaller
      than ACh-evoked currents, and depressed subsequent ACh-evoked currents for
      several minutes, indicating that the compounds are low-efficacy partial agonists
      that potently desensitize the receptors. Much lower concentrations of
      insecticides applied in the bath for longer periods did not activate currents,
      but inhibited ACh-evoked currents via desensitization of the receptors.
      Previously described fast- and slowly-desensitizing nACh currents, I(ACh1) and
      I(ACh2) respectively, were each found to consist of two components with differing
      sensitivities to the insecticides. Imidacloprid applied in the bath desensitized
      high-sensitivity components, I(ACh1H) and I(ACh2H) with IC(50)s of 0.18 and 0.13
      pM, respectively. It desensitized the low-sensitivity slowly desensitizing
      component, I(ACh2L), with an IC(50) of 2.6 nM, while a component of the fast
      desensitizing current, I(ACh1L), was least sensitive, with an IC(50) of 81 nM
      I(ACh1L) appeared to be insensitive to the three sulfoximines tested, whereas all
      three sulfoximines potently desensitized I(ACh1H) and both slowly desensitizing
      components, with IC(50)s between 2 and 7 nM. We conclude that selective
      desensitization of certain nAChR subtypes can account for the insecticidal
      actions of imidacloprid and sulfoximines in stick insects.

PMID- 21878390
TI  - Molecular and functional characterisation of resilin across three insect orders.
AB  - Resilin is an important elastomeric protein of insects, with roles in the storage
      and release of energy during a variety of different functional categories
      including flight and jumping. To date, resilin genes and protein function have
      been characterised only in a small number of flying insects, despite their
      importance in fleas and other jumping insects. Microscopy and immunostaining
      studies of resilin in flea demonstrate the presence of resilin pads in the
      pleural arch at the top of the hind legs, a region responsible for the flea's
      jumping ability. A degenerate primer approach was used to amplify resilin gene
      transcripts from total RNA isolated from flea (Ctenocephalides felis), buffalo
      fly (Haematobia irritans exigua) and dragonfly (Aeshna sp.) pharate adults, and
      full-length transcripts were successfully isolated. Two isoforms (A and B) were
      amplified from each of flea and buffalo fly, and isoform B only in dragonfly.
      Flea and buffalo fly isoform B transcripts were expressed in an Escherichia coli
      expression system, yielding soluble recombinant proteins Cf-resB and Hi-resB
      respectively. Protein structure and mechanical properties of each protein before
      and after crosslinking were assessed. This study shows that resilin gene and
      protein sequences are broadly conserved and that crosslinked recombinant resilin
      proteins share similar mechanical properties from flying to jumping insects. A
      combined use of degenerate primers and polyclonal sera will likely facilitate
      characterisation of resilin genes from other insect and invertebrate orders.

PMID- 21878391
TI  - A comparison between rectal and colonic biopsies to detect Lewy pathology in
      Parkinson's disease.
AB  - We have shown that routine biopsies of the ascending colon obtained at
      colonoscopy allow the detection of Lewy neurites (LN) in the enteric nervous
      system (ENS) of Parkinson's disease (PD) patients. Although colonoscopy is a
      relatively safe procedure, it requires colon preparation and anesthesia. The
      present study was therefore undertaken to evaluate whether descending colon and
      rectal biopsies that are obtainable by rectosigmoidoscopy allow the detection of
      Lewy pathology in the ENS. A total of 9 controls and 26 PD patients were included
      and analyzed. Two biopsies were taken from the ascending, descending colon and
      rectum during the course of a total colonoscopy. Immunohistochemical analysis was
      performed using antibodies against phosphorylated alpha-synuclein to detect LN
      and neurofilaments 200 kDa to label the neuronal structures. Biopsies from
      ascending, descending colon and rectum were morphologically comparable. LN were
      detected in the biopsies of ascending colon in 17 PD patients (65%), of
      descending colon in 11 patients (42%) and of rectum in only 6 patients (23%). No
      LN were seen in control biopsies. Our results show that Lewy pathology follows a
      rostrocaudal distribution in the colon and rectum of PD patients. Therefore,
      rectal biopsies have substantially lower sensitivity than ascending colon
      biopsies to detect Lewy pathology in the gut.

PMID- 21878392
TI  - Strain differences in seizure-induced cell death following pilocarpine-induced
      status epilepticus.
AB  - Mouse strains differ from one another in their susceptibility to seizure-induced
      excitotoxic cell death. Previously, we have demonstrated that mature inbred
      strains of mice show remarkable genetic differences in susceptibility to the
      neuropathological consequences of seizures in the kainate model of status
      epilepticus. At present, while the cellular mechanisms underlying strain
      dependent differences in susceptibility remain unclear, some of this variation is
      assumed to have a genetic basis. However, it remains unclear whether strain
      differences in susceptibility to seizure-induced cell death observed following
      kainate administration are observed following systemic administration of other
      chemoconvulsants. In rodents, the cholinomimetic convulsant pilocarpine is widely
      used to induce status epilepticus (SE), followed by hippocampal damage and
      spontaneous recurrent seizures, resembling temporal lobe epilepsy. This model has
      initially been described in rats, but is increasingly used in mice. We
      characterized neuronal pathologies after pilocarpine-induced status epilepticus
      (SE) in eight inbred strains of mice focusing on the hippocampus. A ramping-up
      dose protocol for pilocarpine was used and behavior was monitored for 4-5 h.
      While we did not observe any significant differences in seizure latency or
      duration to pilocarpine among the inbred strains, we did observe a significant
      difference in susceptibility to the neuropathological consequences of pilocarpine
      induced SE. Of the eight genetically diverse mouse strains screened for
      pilocarpine-induced status, BALB/cJ and BALB/cByJ were the only two strains that
      were resistant to the neuropathological consequences of seizure-induced cell
      death. Additional studies of these murine strains may be useful for investigating
      genetic influences on pilocarpine-induced status epilepticus.

PMID- 21878393
TI  - Isolation, folding and structural investigations of the amino acid transporter
      OEP16.
AB  - Membrane proteins compose more than 30% of all proteins in the living cell.
      However, many membrane proteins have low abundance in the cell and cannot be
      isolated from natural sources in concentrations suitable for structure analysis.
      The overexpression, reconstitution, and stabilization of membrane proteins are
      complex and remain a formidable challenge in membrane protein characterization.
      Here we describe a novel, in vitro folding procedure for a cation-selective
      channel protein, the outer envelope membrane protein 16 (OEP16) of pea
      chloroplast, overexpressed in Escherichia coli in the form of inclusion bodies.
      The protein is purified and then folded with detergent on a Ni-NTA affinity
      column. Final concentrations of reconstituted OEP16 of up to 24 mg/ml have been
      achieved, which provides samples that are sufficient for structural studies by
      NMR and crystallography. Reconstitution of OEP16 in detergent micelles was
      monitored by circular dichroism, fluorescence, and NMR spectroscopy. Tryptophan
      fluorescence spectra of heterologous expressed OEP16 in micelles are similar to
      spectra of functionally active OEP16 in liposomes, which indicates folding of the
      membrane protein in detergent micelles. CD spectroscopy studies demonstrate a
      folded protein consisting primarily of alpha-helices. 15N-HSQC NMR spectra also
      provide evidence for a folded protein. We present here a convenient, effective
      and quantitative method to screen large numbers of conditions for optimal protein
      stability by using microdialysis chambers in combination with fluorescence
      spectroscopy. Recent collection of multidimensional NMR data at 500, 600 and 800
      MHz demonstrated that the protein is suitable for structure determination by NMR
      and stable for weeks during data collection.

PMID- 21878394
TI  - Variation of the gene coding for DARPP-32 (PPP1R1B) and brain connectivity during
      associative emotional learning.
AB  - Associative emotional learning, which is important for the social emotional
      functioning of individuals and is often impaired in psychiatric illnesses, is in
      part mediated by dopamine and glutamate pathways in the brain. The protein DARPP
      32 is involved in the regulation of dopaminergic and glutaminergic signaling.
      Consequently, it has been suggested that the haplotypic variants of the gene
      PPP1R1B that encodes DARPP-32 are associated with working memory and emotion
      processing. We hypothesized that PPP1R1B should have a significant influence on
      the network of brain regions involved in associative emotional learning that are
      rich in DARPP-32, namely the striatum, prefrontal cortex (comprising the medial
      frontal gyrus and inferior frontal gyrus (IFG)), amygdala and parahippocampal
      gyrus (PHG). Dynamic causal models were applied to functional MRI data to
      investigate how brain connectivity during an associative emotional learning task
      is affected by different single-nucleotide polymorphisms (SNPs) of PPP1R1B:
      rs879606, rs907094 and rs3764352. Compared to heterozygotes, homozygotes with GTA
      alleles displayed increased intrinsic connectivity between the IFG and PHG, as
      well as increased excitability of the PHG for negative emotional stimuli. We have
      also elucidated the directionality of these genetic influences. Our data suggest
      that homozygotes with GTA alleles involve stronger functional connections between
      brain areas in order to maintain activation of these regions. Homozygotes might
      engage a greater degree of motivational learning and integration of information
      to perform the emotional learning task correctly. We conclude that PPP1R1B is
      associated with the neural network involved in associative emotional learning.

PMID- 21878395
TI  - Squeezing lemons in the bathroom: contextual information modulates action
      recognition.
AB  - Most every day actions take place in domestic rooms that are specific for certain
      classes of actions. Contextual information derived from domestic settings may
      therefore influence the efficiency of action recognition. The present studies
      investigated whether action recognition is modulated by compatibility of the
      context an action is embedded in. To this end, subjects watched video clips of
      actions performed in compatible, incompatible, and neutral contexts. Recognition
      was significantly slower when actions took place in an incompatible as compared
      to a compatible or a neutral context (Experiment 1). Functional MRI revealed
      increased activation for incompatible context in Brodmann Areas (BA) 44, 45, and
      47 of the left ventrolateral prefrontal cortex (vlPFC; Experiment 2). Results
      suggest that contextual information - even when task-irrelevant - informs a high
      processing level of action analysis. In particular, the functional profiles
      assigned to these prefrontal regions suggest that contextual information
      activates associated action representations as a function of (in-)compatibility.
      Thus, incompatibility effects may reflect the attempt to resolve the conflict
      between action and context by embedding the presented action step into an
      overarching action that is again compatible with the provided context.

PMID- 21878396
TI  - Abstraction of complex concepts with a refined partial-area taxonomy of SNOMED.
AB  - An algorithmically-derived abstraction network, called the partial-area taxonomy,
      for a SNOMED hierarchy has led to the identification of concepts considered
      complex. The designation "complex" is arrived at automatically on the basis of
      structural analyses of overlap among the constituent concept groups of the
      partial-area taxonomy. Such complex concepts, called overlapping concepts,
      constitute a tangled portion of a hierarchy and can be obstacles to users trying
      to gain an understanding of the hierarchy's content. A new methodology for
      partitioning the entire collection of overlapping concepts into singly-rooted
      groups, that are more manageable to work with and comprehend, is presented.
      Different kinds of overlapping concepts with varying degrees of complexity are
      identified. This leads to an abstract model of the overlapping concepts called
      the disjoint partial-area taxonomy, which serves as a vehicle for enhanced, high
      level display. The methodology is demonstrated with an application to SNOMED's
      Specimen hierarchy. Overall, the resulting disjoint partial-area taxonomy offers
      a refined view of the hierarchy's structural organization and conceptual content
      that can aid users, such as maintenance personnel, working with SNOMED. The
      utility of the disjoint partial-area taxonomy as the basis for a SNOMED auditing
      regimen is presented in a companion paper.

PMID- 21878397
TI  - Molecular epidemiology and genetic diversity of Mycobacterium tuberculosis
      complex in the Cross River State, Nigeria.
AB  - This study provides with a first insight on Mycobacterium tuberculosis complex
      epidemiology and genetic diversity in the Cross River State, Nigeria. Starting
      with 137 smear positive patients recruited over a period of 12months (June 2008
      to May 2009), we obtained 97 pure mycobacterial isolates out of which 81 (83.5%)
      were identified as M. tuberculosis complex. Genotyping revealed a total of 27
      spoligotypes patterns with 10 clusters (n=64% or 79% of clustered isolates, 2-32
      isolates/cluster), with patients in the age group range 25-34 years being
      significantly associated with shared-type pattern SIT61 (p=0.019). Comparison
      with SITVIT2 database showed that with the exception of a single cluster
      (SIT727/H1), all other clusters observed were representative of West Africa; the
      two main lineages involved were LAM10-CAM (n=42/81% or 51.8%) of M. tuberculosis
      and AFRI_2 sublineage of Mycobacterium africanum (n=27/81% or 33.3%). Subsequent
      12-loci MIRU typing resulted in a total of 13 SIT/MIT clusters (n=52 isolates, 2
      9 isolates per cluster), with a resulting recent n-1 transmission rate of 48.1%.
      Available drug-susceptibility testing (DST) results for 58/81 clinical isolates
      revealed 6/58% or 10.4% cases of multiple drug-resistance (MDR); 5/6 MDR cases
      were caused by strains belonging to LAM10-CAM lineage (a specific cluster
      SIT61/MIT266 in 4/6 cases, and an orphan spoligotype pattern in 1/6 case).
      Additionally, MIT266 was associated with streptomycin resistance (p=0.016). All
      the six MDRTB isolates were concomitantly resistance to streptomycin and
      ethambutol; however, 4/6 MDR strains with identical MIRU patterns were
      characterized by consecutive strain numbers hence the possibility of laboratory
      cross contamination could not be excluded in 3/4 serial cases. The present
      preliminary study underlines the usefulness of spoligotyping and 12-loci MIRU
      VNTRs to establish a baseline of circulating genotypic lineages of M.
      tuberculosis complex in Nigeria.

PMID- 21878398
TI  - Mechanical testing of electrospun PCL fibers.
AB  - Poly(epsilon-caprolactone) (PCL) fibers ranging from 250 to 700 nm in diameter
      were produced by electrospinning a polymer tetrahydrofuran/N,N-dimethylformamide
      solution. The mechanical properties of the fibrous scaffolds and individual
      fibers were measured by different methods. The Young's moduli of the scaffolds
      were determined using macro-tensile testing equipment, whereas single fibers were
      mechanically tested using a nanoscale three-point bending method, based on atomic
      force microscopy and force spectroscopy analyses. The modulus obtained by tensile
      testing eight different fiber scaffolds was 3.8+/-0.8 MPa. Assuming that PCL
      fibers can be described by the bending model of isotropic materials, a Young's
      modulus of 3.7+/-0.7 GPa was determined for single fibers. The difference of
      three orders of magnitude observed in the moduli of fiber scaffolds vs. single
      fibers can be explained by the lacunar and random structure of the scaffolds.

PMID- 21878399
TI  - Evolution of load transfer between hydroxyapatite and collagen during creep
      deformation of bone.
AB  - While the matrix/reinforcement load-transfer occurring at the micro- and
      nanoscale in nonbiological composites subjected to creep deformation is well
      understood, this topic has been little studied in biological composites such as
      bone. Here, for the first time in bone, the mechanisms of time-dependent load
      transfer occurring at the nanoscale between the collagen phase and the
      hydroxyapatite (HAP) platelets are studied. Bovine cortical bone samples are
      subjected to synchrotron X-ray diffraction to measure in situ the evolution of
      elastic strains in the crystalline HAP phase and the evolution of viscoelastic
      strains accumulating in the mineralized collagen fibrils under creep conditions
      at body temperature. For a constant compressive stress, both types of strains
      increase linearly with time. This suggests that bone, as it deforms
      macroscopically, is behaving as a traditional composite, shedding load from the
      more compliant, viscoelastic collagen matrix to the reinforcing elastic HAP
      platelets. This behavior is modeled by finite-element simulation carried out at
      the fibrillar level.

PMID- 21878400
TI  - A quantitative PCR assay for the detection and quantification of Shiga toxin
      producing Escherichia coli (STEC) in minced beef and dairy products.
AB  - Shiga toxin (Stx)-producing Escherichia coli (STEC) are amongst major causes of
      food-borne infectious diseases and outbreaks. A new quantitative PCR (qPCR) assay
      was designed to detect all known stx gene subtypes in a single reaction,
      including the most distant variant stx2f. Performance of this assay was evaluated
      in combination with two different internal amplification controls (IAC), a
      competitive one specific for the assay and a universal IAC based on plasmid
      pUC19. The qPCR assay was 100% specific and showed analytical sensitivity of two
      STEC genome copies per reaction. The diagnostic approach proposed, combining
      enrichment, automated DNA extraction and qPCR detection, could reliably detect
      the presence of STEC in minced beef and cheese inoculated before enrichment at <4
      CFU per 25 g. A comparative study performed on 240 minced beef and 113 raw milk
      cheese samples demonstrated that the method developed was as effective as two PCR
      screening assays used routinely in our laboratory to detect STEC. The new assay
      also proved to be appropriate for the direct quantification of STEC in milk and
      minced meat. It was found to be quantitative over a five log dynamic range, from
      4 * 106 to 40 CFU/mL for milk and from 107 to 102 CFU/g for minced beef. In
      conclusion, the qPCR assay developed here represents a valuable tool for rapid
      detection and quantification of STEC in foods such as minced beef and dairy
      products as it ensures a high sensitivity and an optimal STEC diagnostic
      spectrum, taking into account the genetic stx variability observed in STEC
      population.

PMID- 21878401
TI  - Physical development in patients with phenylketonuria on dietary treatment: a
      retrospective study.
AB  - OBJECTIVES: To evaluate the growth and physical development in patients with
      phenylalanine hydroxylase deficiency who follow exclusively dietary treatment.
      METHODS: Anthropometric measurements of 160 patients with hyperphenylalaninemia
      who were followed at our center over a 25 year period were obtained. Only
      patients treated exclusively with a protein-restrictive diet supplemented with
      amino acid mixtures were included. Height, weight and body mass index were
      measured at birth, at diagnosis, at 6 and 12 months of age, and annually until 18
      years of age in patients with phenylketonuria or until 9 years of age in patients
      with mild hyperphenylalaninemia and compared to official national reference
      values. The final height of PKU patients was also compared to their expected
      family height. RESULTS: The analysis of z scores suggested no significant
      differences in physical development between PKU patients and the healthy
      population during the study period. The final height of PKU patients revealed
      that they were 2 to 4 cm taller than expected when compared to the mean family
      height (p<0.001). The mean weight and BMI at puberty suggested that many patients
      with severe PKU, but not other phenotypes, were overweight during this period.
      CONCLUSION: Physical development can be optimal in PKU patients regardless of
      their phenotype and the severity of the diet. A tendency to excessive weight gain
      is seen in adolescence in the most severe phenotypes.

PMID- 21878402
TI  - Multiscale modeling and simulation of the cardiac fiber architecture for DMRI.
AB  - Cardiac fiber architecture plays an important role in the study of mechanical and
      electrical properties of the wall of the human heart, but still remains to be
      elucidated. This paper proposes to investigate, in a multiscale manner, how the
      arrangement patterns and morphological heterogeneity of cardiac myocytes
      influence the fibers orientation. To this end, different virtual cardiac fiber
      structures are modeled, and diffusion tensor imaging at multiple scales are
      simulated using the Monte Carlo method. The results show that the proposed
      modeling and simulation allow us to quantitatively describe the variation of the
      measured tissue properties (fiber orientation and fractional anisotropy) as a
      function of the observation scale.

PMID- 21878403
TI  - Multiscale modeling of circular and elliptical particles in laminar shear flow.
AB  - Drug delivery systems for cancer prevention and pain management have been
      improved related to classical cancer chemotherapy. Nanotechnology with
      nanoparticles offers new ways in transport of drug molecules and contrast agents
      by the blood flow through the circulatory system. In this study, we use
      multiscale mesoscopic bridging procedure of the finite elements (FE) coupled with
      dissipative particle dynamics (DPD) and lattice Boltzmann (LB) method to model
      the motion of circular and elliptical particles in a 2-D laminar flow. Four
      examples are considered: 1) one sedimenting cylinder in a channel, 2) two
      sedimenting cylinders in a channel, 3) motion of four elliptical particles in a
      linear shear flow, and 4) motion of circular and elliptical particle in the
      arterial bifurcation geometry. A good agreement with solution from the literature
      available was found. These results show that the multiscale approach with coupled
      FE and DPD/LB methods can effectively be applied to model motion of
      micro/nanoparticles for a drug delivery system.

PMID- 21878404
TI  - An estimate of the dispersion of repolarization times based on a biophysical
      model of the ECG.
AB  - Temporal heterogeneity of ventricular repolarization is a key quantity for the
      development of ventricular reentrant arrhythmia. In this paper, we introduce the
      V-index, a novel ECG-based estimator of the standard deviation of ventricular
      myocytes' repolarization times s(theta). Differently from other ECG metrics of
      repolarization heterogeneity, the V-index was derived from the analysis of a
      biophysical model of the ECG, where repolarization is described by the dominant T
      wave (DTW) paradigm. The model explains the shape of T-waves in each lead as a
      projection of a main waveform (the DTW) and its derivatives weighted by scalars,
      the lead factors. A mathematical formula is derived to link the heterogeneity of
      ventricular repolarization s(theta) and the V-index. The formula was verified
      using synthetic 12-lead ECGs generated with a direct electrophysiological model
      for increasing values of s(theta) (in the range 20-70 ms). A linear relationship
      between the V-index and s(theta) was observed, V ~ 0.675 s(theta) + 1.8 ms (R(2)
      = 0.9992). Finally, 68 ECGs from the E-OTH-12-0068-010 database of the Telemetric
      and Holter ECG Warehouse were analyzed. The V-index coherently increased after
      sotalol administration, a drug known to have QT-prolonging potential (p <<
      0.001).

PMID- 21878405
TI  - An atrioventricular node model for analysis of the ventricular response during
      atrial fibrillation.
AB  - This paper introduces a model of the atrioventricular node function during atrial
      fibrillation (AF), and describes the related ECG-based estimation method. The
      proposed model is defined by parameters that characterize the arrival rate of
      atrial impulses, the probability of an impulse choosing either one of the two
      atrioventricular nodal pathways, the refractory periods of these pathways, and
      the prolongation of the refractory periods. These parameters are estimated from
      the RR intervals using maximum likelihood estimation, except for the shorter
      refractory period which is estimated from the RR interval Poincare plot, and the
      mean arrival rate of atrial impulses by the AF frequency. Simulations indicated
      that 200-300 RR intervals are generally needed for the estimates to be accurate.
      The model was evaluated on 30-min ECG segments from 36 AF patients. The results
      showed that 88% of the segments can be accurately modeled when the estimated
      probability density function (PDF) and an empirical PDF were at least 80% in
      agreement. The model parameters were estimated during head-up tilt test to assess
      differences caused by sympathetic stimulation. Both refractory periods decreased
      as a result of stimulation, and the likelihood of an impulse choosing the pathway
      with the shorter refractory period increased.

PMID- 21878406
TI  - A preliminary model of gastrointestinal electromechanical coupling.
AB  - Gastrointestinal (GI) motility is coordinated by several cooperating mechanisms,
      including electrical slow wave activity, the enteric nervous system (ENS), and
      other factors. Slow waves generated in interstitial cells of Cajal (ICC)
      depolarize smooth muscle cells (SMC), generating basic GI contractions. This
      unique electrical coupling presents an added layer of complexity to GI
      electromechanical models, and a current barrier to further progress is the lack
      of a framework for ICC-SMC-contraction coupling. In this study, an initial
      framework for the electromechanical coupling was developed in a 2-D model. At
      each solution step, the slow wave propagation was solved first and  [Ca(2+)](i)
      in the SMC model was related to a  Ca(2+)-tension-extension relationship to
      simulate active contraction. With identification of more GI-specific constitutive
      laws and material parameters, the ICC-SMC-contraction approach may underpin
      future GI electromechanical models of health and disease states.

PMID- 21878407
TI  - An anisotropic microsphere-based approach for fiber orientation adaptation in
      soft tissue.
AB  - Evolutionary processes in biological tissue, such as adaptation or remodeling,
      represent an enterprising area of research. In this paper, we present a
      multiscale model for the remodeling of fibered structures, such as bundles of
      collagen fibrils. With this aim, we introduce a von Mises statistical
      distribution function to account for the directional dispersion of the fibrils,
      and we remodel the underlying fibrils by changing their orientation. To
      numerically compute this process, we make use of the microsphere approach, which
      provides a useful multiscale tool for homogenizing the microstructure behavior,
      related to the fibrils of the bundle, in the macroscale of the problem. The
      results show how the fibrils respond to the stimulus by reorientation of their
      structure. This process leads to a stiffer material eventually reaching a
      stationary state. These results are in agreement with those reported in the
      literature, and they characterize the adaptation of biological tissue to external
      stimuli.

PMID- 21878408
TI  - Novel estimation of the electrical bioimpedance using the local polynomial
      method. Application to in vivo real-time myocardium tissue impedance
      characterization during the cardiac cycle.
AB  - Classical measurements of myocardium tissue electrical impedance for
      characterizing the morphology of myocardium cells, as well as cell membranes
      integrity and intra/extra cellular spaces, are based on the frequency-sweep
      electrical impedance spectroscopy (EIS) technique. In contrast to the frequency
      sweep EIS approach, measuring with broadband signals, i.e., multisine
      excitations, enables to collect, simultaneously, multiple myocardium tissue
      impedance data in a short measuring time. However, reducing the measuring time
      makes the measurements to be prone to the influence of the transients introduced
      by noise and the dynamic time-varying properties of tissue. This paper presents a
      novel approach for the impedance-frequency-response estimation based on the local
      polynomial method (LPM). The fast LPM version presented rejects the leakage
      error's influence on the impedance frequency response when measuring electrical
      bioimpedance in a short time. The theory is supported by a set of validation
      measurements. Novel preliminary experimental results obtained from real-time in
      vivo healthy myocardium tissue impedance characterization within the cardiac
      cycle using multisine excitation are reported.

PMID- 21878409
TI  - A multiscale framework based on the physiome markup languages for exploring the
      initiation of osteoarthritis at the bone-cartilage interface.
AB  - The initiation of osteoarthritis (OA) has been linked to the onset and
      progression of pathologic mechanisms at the cartilage-bone interface. Most
      importantly, this degenerative disease involves cross-talk between the cartilage
      and subchondral bone environments, so an informative model should contain the
      complete complex. In order to evaluate this process, we have developed a
      multiscale model using the open-source ontologies developed for the Physiome
      Project with cartilage and bone descriptions at the cellular, micro, and macro
      levels. In this way, we can effectively model the influence of whole body
      loadings at the macro level and the influence of bone organization and
      architecture at the micro level, and have cell level processes that determine
      bone and cartilage remodeling. Cell information is then passed up the spatial
      scales to modify micro architecture and provide a macro spatial characterization
      of cartilage inflammation. We evaluate the framework by linking a common knee
      injury (anterior cruciate ligament deficiency) to proinflammatory mediators as a
      possible pathway to initiate OA. This framework provides a "virtual bone
      cartilage" tool for evaluating hypotheses, treatment effects, and disease onset
      to inform and strengthen clinical studies.

PMID- 21878410
TI  - Multi-channel microstrip transceiver arrays using harmonics for high field MR
      imaging in humans.
AB  - Radio-frequency (RF) transceiver array design using primary and higher order
      harmonics for in vivo parallel magnetic resonance imaging imaging (MRI) and
      spectroscopic imaging is proposed. The improved electromagnetic decoupling
      performance, unique magnetic field distributions and high-frequency operation
      capabilities of higher-order harmonics of resonators would benefit transceiver
      arrays for parallel MRI, especially for ultrahigh field parallel MRI. To
      demonstrate this technique, microstrip transceiver arrays using first and second
      harmonic resonators were developed for human head parallel imaging at 7T. Phantom
      and human head images were acquired and evaluated using the GRAPPA reconstruction
      algorithm. The higher-order harmonic transceiver array design technique was also
      assessed numerically using FDTD simulation. Compared with regular primary
      resonance transceiver designs, the proposed higher-order harmonic technique
      provided an improved g-factor and increased decoupling among resonant elements
      without using dedicated decoupling circuits, which would potentially lead to a
      better parallel imaging performance and ultimately faster and higher quality
      imaging. The proposed technique is particularly suitable for densely spaced
      transceiver array design where the increased mutual inductance among the elements
      becomes problematic. In addition, it also provides a simple approach to readily
      upgrade the channels of a conventional primary resonator microstrip array to a
      larger number for faster imaging.

PMID- 21878411
TI  - Joint modeling of anatomical and functional connectivity for population studies.
AB  - We propose a novel probabilistic framework to merge information from diffusion
      weighted imaging tractography and resting-state functional magnetic resonance
      imaging correlations to identify connectivity patterns in the brain. In
      particular, we model the interaction between latent anatomical and functional
      connectivity and present an intuitive extension to population studies. We employ
      the EM algorithm to estimate the model parameters by maximizing the data
      likelihood. The method simultaneously infers the templates of latent connectivity
      for each population and the differences in connectivity between the groups. We
      demonstrate our method on a schizophrenia study. Our model identifies significant
      increases in functional connectivity between the parietal/posterior cingulate
      region and the frontal lobe and reduced functional connectivity between the
      parietal/posterior cingulate region and the temporal lobe in schizophrenia. We
      further establish that our model learns predictive differences between the
      control and clinical populations, and that combining the two modalities yields
      better results than considering each one in isolation.

PMID- 21878412
TI  - Accuracy of carotid strain estimates from ultrasonic wall tracking: a study based
      on multiphysics simulations and in vivo data.
AB  - We used a multiphysics model to assess the accuracy of carotid strain estimates
      derived from a 1-D ultrasonic wall tracking algorithm. The presented tool
      integrates fluid-structure interaction (FSI) simulations with an ultrasound
      simulator (Field II), which allows comparison of the ultrasound (US) images with
      a ground truth. Field II represents tissue as random points on which US waves
      reflect and whose position can be updated based on the flow field and vessel wall
      deformation from FSI. We simulated the RF-signal of a patient-specific carotid
      bifurcation, including the blood pool as well as the vessel wall and surrounding
      tissue. Distension estimates were obtained from a wall tracking algorithm using
      tracking points at various depths within the wall, and further processed to
      assess radial and circumferential strain. The simulated data demonstrated that
      circumferential strain can be estimated with reasonable accuracy (especially for
      the common carotid artery and at the lumen-intima and media-adventitia
      interface), but the technique does not allow to reliably assess intra-arterial
      radial strain. These findings were supported by in vivo data of 10 healthy
      adults, showing similar circumferential and radial strain profiles throughout the
      arterial wall. We concluded that these deviations are present due to the complex
      3-D vessel wall deformation, the presence of specular reflections and, to a
      lesser extent, the spatially varying beam profile, with the error depending on
      the phase in the cardiac cycle and the scanning location.

PMID- 21878413
TI  - Minimum-volume-constrained nonnegative matrix factorization: enhanced ability of
      learning parts.
AB  - Nonnegative matrix factorization (NMF) with minimum-volume-constraint (MVC) is
      exploited in this paper. Our results show that MVC can actually improve the
      sparseness of the results of NMF. This sparseness is L(0)-norm oriented and can
      give desirable results even in very weak sparseness situations, thereby leading
      to the significantly enhanced ability of learning parts of NMF. The close
      relation between NMF, sparse NMF, and the MVC_NMF is discussed first. Then two
      algorithms are proposed to solve the MVC_NMF model. One is called quadratic
      programming_MVC_NMF (QP_MVC_NMF) which is based on quadratic programming and the
      other is called negative glow_MVC_NMF (NG_MVC_NMF) because it uses multiplicative
      updates incorporating natural gradient ingeniously. The QP_MVC_NMF algorithm is
      quite efficient for small-scale problems and the NG_MVC_NMF algorithm is more
      suitable for large-scale problems. Simulations show the efficiency and validity
      of the proposed methods in applications of blind source separation and human face
      images analysis.

PMID- 21878414
TI  - RRED indices: reduced reference entropic differencing for image quality
      assessment.
AB  - We study the problem of automatic "reduced-reference" image quality assessment
      (QA) algorithms from the point of view of image information change. Such changes
      are measured between the reference- and natural-image approximations of the
      distorted image. Algorithms that measure differences between the entropies of
      wavelet coefficients of reference and distorted images, as perceived by humans,
      are designed. The algorithms differ in the data on which the entropy difference
      is calculated and on the amount of information from the reference that is
      required for quality computation, ranging from almost full information to almost
      no information from the reference. A special case of these is algorithms that
      require just a single number from the reference for QA. The algorithms are shown
      to correlate very well with subjective quality scores, as demonstrated on the
      Laboratory for Image and Video Engineering Image Quality Assessment Database and
      the Tampere Image Database. Performance degradation, as the amount of information
      is reduced, is also studied.

PMID- 21878415
TI  - Antialiasing filter design for subpixel downsampling via frequency-domain
      analysis.
AB  - In this paper, we are concerned with image downsampling using subpixel techniques
      to achieve superior sharpness for small liquid crystal displays (LCDs). Such a
      problem exists when a high-resolution image or video is to be displayed on low
      resolution display terminals. Limited by the low-resolution display, we have to
      shrink the image. Signal-processing theory tells us that optimal decimation
      requires low-pass filtering with a suitable cutoff frequency, followed by
      downsampling. In doing so, we need to remove many useful image details causing
      blurring. Subpixel-based downsampling, taking advantage of the fact that each
      pixel on a color LCD is actually composed of individual red, green, and blue
      subpixel stripes, can provide apparent higher resolution. In this paper, we use
      frequency-domain analysis to explain what happens in subpixel-based downsampling
      and why it is possible to achieve a higher apparent resolution. According to our
      frequency-domain analysis and observation, the cutoff frequency of the low-pass
      filter for subpixel-based decimation can be effectively extended beyond the
      Nyquist frequency using a novel antialiasing filter. Applying the proposed
      filters to two existing subpixel downsampling schemes called direct subpixel
      based downsampling (DSD) and diagonal DSD (DDSD), we obtain two improved schemes,
      i.e., DSD based on frequency-domain analysis (DSD-FA) and DDSD based on frequency
      domain analysis (DDSD-FA). Experimental results verify that the proposed DSD-FA
      and DDSD-FA can provide superior results, compared with existing subpixel or
      pixel-based downsampling methods.

PMID- 21878416
TI  - Iris recognition using possibilistic fuzzy matching on local features.
AB  - In this paper, we propose a novel possibilistic fuzzy matching strategy with
      invariant properties, which can provide a robust and effective matching scheme
      for two sets of iris feature points. In addition, the nonlinear normalization
      model is adopted to provide more accurate position before matching. Moreover, an
      effective iris segmentation method is proposed to refine the detected inner and
      outer boundaries to smooth curves. For feature extraction, the Gabor filters are
      adopted to detect the local feature points from the segmented iris image in the
      Cartesian coordinate system and to generate a rotation-invariant descriptor for
      each detected point. After that, the proposed matching algorithm is used to
      compute a similarity score for two sets of feature points from a pair of iris
      images. The experimental results show that the performance of our system is
      better than those of the systems based on the local features and is comparable to
      those of the typical systems.

PMID- 21878417
TI  - tOWL: a temporal Web Ontology Language.
AB  - Through its interoperability and reasoning capabilities, the Semantic Web opens a
      realm of possibilities for developing intelligent systems on the Web. The Web
      Ontology Language (OWL) is the most expressive standard language for modeling
      ontologies, the cornerstone of the Semantic Web. However, up until now, no
      standard way of expressing time and time-dependent information in OWL has been
      provided. In this paper, we present a temporal extension of the very expressive
      fragment  SHIN(D) of the OWL Description Logic language, resulting in the
      temporal OWL language. Through a layered approach, we introduce three extensions:
      1) concrete domains, which allow the representation of restrictions using
      concrete domain binary predicates; 2) temporal representation , which introduces
      time points, relations between time points, intervals, and Allen's 13 interval
      relations into the language; and 3) timeslices/fluents, which implement a
      perdurantist view on individuals and allow for the representation of complex
      temporal aspects, such as process state transitions. We illustrate the
      expressiveness of the newly introduced language by using an example from the
      financial domain.

PMID- 21878418
TI  - Fuzzy integral-based gaze control architecture incorporated with modified
      univector field-based navigation for humanoid robots.
AB  - When a humanoid robot moves in a dynamic environment, a simple process of
      planning and following a path may not guarantee competent performance for dynamic
      obstacle avoidance because the robot acquires limited information from the
      environment using a local vision sensor. Thus, it is essential to update its
      local map as frequently as possible to obtain more information through gaze
      control while walking. This paper proposes a fuzzy integral-based gaze control
      architecture incorporated with the modified-univector field-based navigation for
      humanoid robots. To determine the gaze direction, four criteria based on local
      map confidence, waypoint, self-localization, and obstacles, are defined along
      with their corresponding partial evaluation functions. Using the partial
      evaluation values and the degree of consideration for criteria, fuzzy integral is
      applied to each candidate gaze direction for global evaluation. For the effective
      dynamic obstacle avoidance, partial evaluation functions about self-localization
      error and surrounding obstacles are also used for generating virtual dynamic
      obstacle for the modified-univector field method which generates the path and
      velocity of robot toward the next waypoint. The proposed architecture is verified
      through the comparison with the conventional weighted sum-based approach with the
      simulations using a developed simulator for HanSaRam-IX (HSR-IX).

PMID- 21878419
TI  - Limb-state information encoded by peripheral and central somatosensory neurons:
      implications for an afferent interface.
AB  - A major issue to be addressed in the development of neural interfaces for
      prosthetic control is the need for somatosensory feedback. Here, we investigate
      two possible strategies: electrical stimulation of either dorsal root ganglia
      (DRG) or primary somatosensory cortex (S1). In each approach, we must determine a
      model that reflects the representation of limb state in terms of neural
      discharge. This model can then be used to design stimuli that artificially
      activate the nervous system to convey information about limb state to the
      subject. Electrically activating DRG neurons using naturalistic stimulus
      patterns, modeled on recordings made during passive limb movement, evoked
      activity in S1 that was similar to that of the original movement. We also found
      that S1 neural populations could accurately discriminate different patterns of
      DRG stimulation across a wide range of stimulus pulse-rates. In studying the
      neural coding in S1, we also decoded the kinematics of active limb movement using
      multi-electrode recordings in the monkey. Neurons having both proprioceptive and
      cutaneous receptive fields contributed equally to this decoding. Some neurons
      were most informative of limb state in the recent past, but many others appeared
      to signal upcoming movements suggesting that they also were modulated by an
      efference copy signal. Finally, we show that a monkey was able to detect
      stimulation through a large percentage of electrodes implanted in area 2. We
      discuss the design of appropriate stimulus paradigms for conveying time-varying
      limb state information, and the relative merits and limitations of central and
      peripheral approaches.

PMID- 21878420
TI  - Associations of toenail arsenic, cadmium, mercury, manganese, and lead with blood
      pressure in the normative aging study.
AB  - BACKGROUND: Arsenic, cadmium, mercury, and lead are associated with
      cardiovascular disease in epidemiologic research. These associations may be
      mediated by direct effects of the metals on blood pressure (BP) elevation.
      Manganese is associated with cardiovascular dysfunction and hypotension in
      occupational cohorts. OBJECTIVES: We hypothesized that chronic arsenic, cadmium,
      mercury, and lead exposures elevate BP and that manganese lowers BP. METHODS: We
      conducted a cross-sectional analysis of associations between toenail metals and
      BP among older men from the Normative Aging Study (n = 639), using linear
      regression and adjusting for potential confounders. RESULTS: An interquartile
      range increase in toenail arsenic was associated with higher systolic BP [0.93
      mmHg; 95% confidence interval (CI): 0.25, 1.62] and pulse pressure (0.76 mmHg;
      95% CI: 0.22, 1.30). Positive associations between arsenic and BP and negative
      associations between manganese and BP were strengthened in models adjusted for
      other toenail metals. CONCLUSIONS: Our findings suggest associations between BP
      and arsenic and manganese. This may be of public health importance because of
      prevalence of both metal exposure and cardiovascular disease. Results should be
      interpreted cautiously given potential limitations of toenails as biomarkers of
      metal exposure.

PMID- 21878421
TI  - European birth cohorts for environmental health research.
AB  - BACKGROUND: Many pregnancy and birth cohort studies investigate the health
      effects of early-life environmental contaminant exposure. An overview of existing
      studies and their data is needed to improve collaboration, harmonization, and
      future project planning. OBJECTIVES: Our goal was to create a comprehensive
      overview of European birth cohorts with environmental exposure data. METHODS:
      Birth cohort studies were included if they a) collected data on at least one
      environmental exposure, b) started enrollment during pregnancy or at birth, c)
      included at least one follow-up point after birth, d) included at least 200
      mother-child pairs, and e) were based in a European country. A questionnaire
      collected information on basic protocol details and exposure and health outcome
      assessments, including specific contaminants, methods and samples, timing, and
      number of subjects. A full inventory can be searched on
      www.birthcohortsenrieco.net. RESULTS: Questionnaires were completed by 37 cohort
      studies of > 350,000 mother-child pairs in 19 European countries. Only three
      cohorts did not participate. All cohorts collected biological specimens of
      children or parents. Many cohorts collected information on passive smoking (n =
      36), maternal occupation (n = 33), outdoor air pollution (n = 27), and
      allergens/biological organisms (n = 27). Fewer cohorts (n = 12-19) collected
      information on water contamination, ionizing or nonionizing radiation exposures,
      noise, metals, persistent organic pollutants, or other pollutants. All cohorts
      have information on birth outcomes; nearly all on asthma, allergies, childhood
      growth and obesity; and 26 collected information on child neurodevelopment.
      CONCLUSION: Combining forces in this field will yield more efficient and
      conclusive studies and ultimately improve causal inference. This impressive
      resource of existing birth cohort data could form the basis for longer-term and
      worldwide coordination of research on environment and child health.

PMID- 21878422
TI  - Interaction between smoking and obesity and the risk of developing breast cancer
      among postmenopausal women: the Women's Health Initiative Observational Study.
AB  - Obesity is a well-established risk factor for postmenopausal breast cancer.
      Recent studies suggest that smoking increases the risk of breast cancer. However,
      the effect of co-occurrence of smoking and obesity on breast cancer risk remains
      unclear. A total of 76,628 women aged 50-79 years enrolled in the Women's Health
      Initiative Observational Study were followed through August 14, 2009. Cox
      proportional hazards regression models were used to estimate hazard ratios and
      95% confidence intervals. Over an average 10.3 years of follow-up, 3,378 incident
      cases of invasive breast cancer were identified. The effect of smoking on the
      risk of developing invasive breast cancer was modified significantly by obesity
      status among postmenopausal women, regardless of whether the obesity status was
      defined by body mass index (P(interaction) = 0.01) or waist circumference
      (P(interaction) = 0.02). A significant association between smoking and breast
      cancer risk was noted in nonobese women (hazard ratio = 1.25, 95% confidence
      interval: 1.05, 1.47) but not in obese women (hazard ratio = 0.96, 95% confidence
      interval: 0.69, 1.34). In conclusion, this study suggests that the effect of
      smoking exposure on breast cancer risk was modified by obesity among
      postmenopausal women. The modification effect did not differ by general versus
      abdominal obesity.

PMID- 21878423
TI  - Association of prenatal exposure to polybrominated diphenyl ethers and infant
      birth weight.
AB  - Polybrominated diphenyl ethers (PBDEs) are a class of persistent compounds that
      have been used as flame retardants in vehicles, household furnishings, and
      consumer electronics. This study examined whether concentrations of PBDEs in
      maternal serum during pregnancy were associated with infant birth weight, length,
      head circumference, and length of gestation. Participants were pregnant women (n
      = 286) enrolled in the Center for the Health Assessment of Mothers and Children
      of Salinas (CHAMACOS) Study, a longitudinal cohort study of low-income,
      predominantly Mexican families living in the Salinas Valley, California. Blood
      samples were collected near the 26th week of pregnancy in 1999-2000, and
      concentrations of 10 PBDE congeners (BDE-17, -28, -47, -66, -85, -99, -100, -153,
      -154, and -183) were measured. Multiple linear regression models were used to
      investigate the association of lipid-adjusted, log(10)-transformed PBDE
      concentrations and birth outcome. In adjusted analyses, negative associations
      with birth weight were seen with BDE-47 (beta = -115 g, 95% confidence interval
      (CI): -229, -2), BDE-99 (beta = -114 g, 95% CI: -225, -4), and BDE-100 (beta = 
      122 g, 95% CI: -235, -9). These findings were diminished slightly and were no
      longer statistically significant when maternal weight gain was included in the
      models. PBDE congeners were not associated with birth length, head circumference,
      or gestational duration.

PMID- 21878424
TI  - Methicillin-resistant Staphylococcus aureus colonization and risk of subsequent
      infection in critically ill children: importance of preventing nosocomial
      methicillin-resistant Staphylococcus aureus transmission.
AB  - BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) colonization is a
      predictor of subsequent infection in hospitalized adults. The risk of subsequent
      MRSA infections in hospitalized children colonized with MRSA is unknown. METHODS:
      Children admitted to an academic medical center's pediatric intensive care unit
      between March 2007 and March 2010 were included in the study. Anterior naris
      swabs were cultured to identify children with MRSA colonization at admission.
      Laboratory databases were queried and National Healthcare Safety Network
      definitions applied to identify patients with MRSA infections during their
      hospitalization or after discharge. RESULTS: The MRSA admission prevalence among
      3140 children was 4.9%. Overall, 56 children (1.8%) developed an MRSA infection,
      including 13 (8.5%) colonized on admission and 43 (1.4%) not colonized on
      admission (relative risk [RR], 5.9; 95% confidence interval [CI], 3.4-10.1). Of
      those, 10 children (0.3%) developed an MRSA infection during their
      hospitalization, including 3 of 153 children (1.9%) colonized on admission and 7
      of 2987 children (0.2%) not colonized on admission (RR, 8.4; 95% CI, 2.7-25.8).
      African-Americans and those with public health insurance were more likely to get
      a subsequent infection (P < .01 and P = .03, respectively). We found that 15
      children acquired MRSA colonization in the pediatric intensive care unit, and 7
      (47%) developed a subsequent MRSA infection. CONCLUSIONS: MRSA colonization is a
      risk factor for subsequent MRSA infection in children. Although MRSA colonized
      children may have lower risks of subsequent infection than adults, children who
      acquire MRSA in the hospital have similarly high rates of infection. Preventing
      transmission of MRSA in hospitalized children should remain a priority.

PMID- 21878425
TI  - Infant rotavirus vaccination may provide indirect protection to older children
      and adults in the United States.
AB  - Following the introduction of rotavirus vaccination in the United States,
      rotavirus and cause-unspecified gastroenteritis discharges significantly
      decreased in 2008 in the 0-4, 5-14, and 15-24-year age groups, with significant
      reductions observed in March, the historic peak rotavirus month, in all age
      groups. We estimate that 15% of the total 66 000 averted hospitalizations and 20%
      of the $204 million in averted direct medical costs attributable to the
      vaccination program were among unvaccinated 5-24 year-olds. This study
      demonstrates a previously unrecognized burden of severe rotavirus in the
      population >5 years and the primacy of very young children in the transmission of
      rotavirus.

PMID- 21878426
TI  - Unexpected benefits of rotavirus vaccination in the United States.

PMID- 21878427
TI  - Longitudinal changes in cardiac function after cisplatin-based chemotherapy for
      testicular cancer.
AB  - BACKGROUND: Cross-sectional studies showed that treatment with cisplatin
      chemotherapy for testicular cancer is associated with an increased incidence of
      cardiac dysfunction. We investigated longitudinal progression of and contributing
      factors to cardiac dysfunction in testicular cancer survivors. PATIENTS AND
      METHODS: Cardiac assessments were carried out before 10 months (range 7-15
      months) and 6.9 years (range 4.9-9.7 years) after start of cisplatin-based
      chemotherapy, consisting of echocardiography [systolic function (left ventricular
      ejection fraction, LVEF), diastolic function (myocardial tissue velocities;
      tissue velocity imaging of early diastole, TVI Et)] and plasma biomarkers (N
      Terminal pro brain natriuretic peptide, NT-proBNP; galectin-3). RESULTS: In 37
      patients [median age 34 years (range 24-51 years)], the incidence of abnormal TVI
      Et increased from 0% at baseline and 4.5% at 10 months (in 27 patients) to 16.7%
      at 6.9 years post-chemotherapy (P = 0.03). One patient developed LVEF <50%; no
      other systolic abnormalities occurred. Hypertension, obesity and age were
      associated with larger decreases in TVI Et. Changes in NT-proBNP and galectin-3
      were not related to echocardiographic abnormalities. CONCLUSIONS: In this
      longitudinal cohort study, we observed a gradual decline in diastolic parameters
      after cisplatin-based chemotherapy for testicular cancer, whereas the rate of
      systolic dysfunction remains low. The association of larger declines in diastolic
      parameters with hypertension and obesity stresses the need to monitor and treat
      cardiovascular risk factors.

PMID- 21878428
TI  - Grading system and management guidelines for dermatitis induced by head and neck
      radiotherapy plus cetuximab: clinical validation required.

PMID- 21878429
TI  - Impact of sunitinib pharmacokinetic monitoring in a patient with metastatic renal
      cell carcinoma undergoing hemodialysis.

PMID- 21878430
TI  - Getting ready to leave: transition readiness in adolescent kidney transplant
      recipients.
AB  - OBJECTIVE: To develop a measure of transition readiness and assess factors
      associated with perceived readiness for transition of healthcare responsibility
      and transfer among adolescent kidney transplant recipients. METHODS: The
      Readiness for Transition Questionnaire (RTQ-teen; RTQ-parent) was created to
      assess overall transition readiness, adolescent healthcare behavior, and familial
      involvement in healthcare. Participants were 48 adolescent kidney transplant
      recipients ages 15-21 years. Thirty-two (66.7%) of the adolescents' caregivers
      also participated. Adolescents completed the RTQ-teen, as well as self-reported
      measures of adherence and barriers to adherence. Parents completed the RTQ
      parent. RESULTS: The RTQ showed good internal consistency, inter rater
      reliability, and demonstrated construct validity. Increased adolescent
      responsibility and decreased parental involvement predicted higher transition
      readiness. Additionally, greater adolescent adherence factors predicted greater
      transition readiness. CONCLUSIONS: The preliminary psychometrics of the RTQ
      appear to be supported. Additional research should evaluate healthcare transition
      programming to identify clinical components related to improved transition
      readiness, adolescent responsibility, and medical outcomes.

PMID- 21878431
TI  - Intra-aortic balloon counterpulsation and infarct size in patients with acute
      anterior myocardial infarction without shock: the CRISP AMI randomized trial.
AB  - CONTEXT: Intra-aortic balloon counterpulsation (IABC) is an adjunct to
      revascularization in patients with cardiogenic shock and reduces infarct size
      when placed prior to reperfusion in animal models. OBJECTIVE: To determine if
      routine IABC placement prior to reperfusion in patients with anterior ST-segment
      elevation myocardial infarction (STEMI) without shock reduces myocardial infarct
      size. DESIGN, SETTING, AND PATIENTS: An open, multicenter, randomized controlled
      trial, the Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial
      Infarction (CRISP AMI) included 337 patients with acute anterior STEMI but
      without cardiogenic shock at 30 sites in 9 countries from June 2009 through
      February 2011. INTERVENTION: Initiation of IABC before primary percutaneous
      coronary intervention (PCI) and continuation for at least 12 hours (IABC plus
      PCI) vs primary PCI alone. MAIN OUTCOME MEASURES: Infarct size expressed as a
      percentage of left ventricular (LV) mass and measured by cardiac magnetic
      resonance imaging performed 3 to 5 days after PCI. Secondary end points included
      all-cause death at 6 months and vascular complications and major bleeding at 30
      days. Multiple imputations were performed for missing infarct size data. RESULTS:
      The median time from first contact to first coronary device was 77 minutes
      (interquartile range, 53 to 114 minutes) for the IABC plus PCI group vs 68
      minutes (interquartile range, 40 to 100 minutes) for the PCI alone group (P =
      .04). The mean infarct size was not significantly different between the patients
      in the IABC plus PCI group and in the PCI alone group (42.1% [95% CI, 38.7% to
      45.6%] vs 37.5% [95% CI, 34.3% to 40.8%], respectively; difference of 4.6% [95%
      CI, -0.2% to 9.4%], P = .06; imputed difference of 4.5% [95% CI, -0.3% to 9.3%],
      P = .07) and in patients with proximal left anterior descending Thrombolysis in
      Myocardial Infarction flow scores of 0 or 1 (46.7% [95% CI, 42.8% to 50.6%] vs
      42.3% [95% CI, 38.6% to 45.9%], respectively; difference of 4.4% [95% CI, -1.0%
      to 9.7%], P = .11; imputed difference of 4.8% [95% CI, -0.6% to 10.1%], P = .08).
      At 30 days, there were no significant differences between the IABC plus PCI group
      and the PCI alone group for major vascular complications (n = 7 [4.3%; 95% CI,
      1.8% to 8.8%] vs n = 2 [1.1%; 95% CI, 0.1% to 4.0%], respectively; P = .09) and
      major bleeding or transfusions (n = 5 [3.1%; 95% CI, 1.0% to 7.1%] vs n = 3
      [1.7%; 95% CI, 0.4% to 4.9%]; P = .49). By 6 months, 3 patients (1.9%; 95% CI,
      0.6% to 5.7%) in the IABC plus PCI group and 9 patients (5.2%; 95% CI, 2.7% to
      9.7%) in the PCI alone group had died (P = .12). CONCLUSION: Among patients with
      acute anterior STEMI without shock, IABC plus primary PCI compared with PCI alone
      did not result in reduced infarct size. TRIAL REGISTRATION: clinicaltrials.gov
      Identifier: NCT00833612.

PMID- 21878432
TI  - Association between serum cathepsin S and mortality in older adults.
AB  - CONTEXT: Experimental data suggest that cathepsin S, a cysteine protease, is
      involved in the complex pathways leading to cardiovascular disease and cancer.
      However, prospective data concerning a potential association between circulating
      cathepsin S levels and mortality are lacking. OBJECTIVE: To investigate
      associations between circulating cathepsin S levels and mortality in 2
      independent cohorts of elderly men and women. DESIGN, SETTING, AND PARTICIPANTS:
      Prospective study using 2 community-based cohorts, the Uppsala Longitudinal Study
      of Adult Men (ULSAM; n = 1009; mean age: 71 years; baseline period: 1991-1995;
      median follow-up: 12.6 years; end of follow-up: 2006) and the Prospective
      Investigation of the Vasculature in Uppsala Seniors (PIVUS; n = 987; 50% women;
      mean age: 70 years; baseline period: 2001-2004; median follow-up: 7.9 years; end
      of follow-up: 2010). Serum samples were used to measure cathepsin S. MAIN OUTCOME
      MEASURE: Total mortality. RESULTS: During follow-up, 413 participants died in the
      ULSAM cohort (incidence rate: 3.59/100 person-years at risk) and 100 participants
      died in the PIVUS cohort (incidence rate: 1.32/100 person-years at risk). In
      multivariable Cox regression models adjusted for age, systolic blood pressure,
      diabetes, smoking status, body mass index, total cholesterol, high-density
      lipoprotein cholesterol, antihypertensive treatment, lipid-lowering treatment,
      and history of cardiovascular disease, higher serum cathepsin S was associated
      with an increased risk for mortality (ULSAM cohort: hazard ratio [HR] for 1-unit
      increase of cathepsin S, 1.04 [95% CI, 1.01-1.06], P = .009; PIVUS cohort: HR for
      1-unit increase of cathepsin S, 1.03 [95% CI, 1.00-1.07], P = .04). In the ULSAM
      cohort, serum cathepsin S also was associated with cardiovascular mortality (131
      deaths; HR for quintile 5 vs quintiles 1-4, 1.62 [95% CI, 1.11-2.37]; P = .01)
      and cancer mortality (148 deaths; HR for 1-unit increase of cathepsin S, 1.05
      [95% CI, 1.01-1.10]; P = .01). CONCLUSIONS: Among elderly individuals in 2
      independent cohorts, higher serum cathepsin S levels were associated with
      increased mortality risk. Additional research is needed to delineate the role of
      cathepsin S and whether its measurement might have clinical utility.

PMID- 21878433
TI  - Need for critical reappraisal of intra-aortic balloon counterpulsation.

PMID- 21878435
TI  - On the cutting edge of acute coronary syndromes: adding oral factor Xa-inhibition
      with darexaban to dual antiplatelet therapy: the RUBY-1 trial.

PMID- 21878437
TI  - Genome-wide association study of circulating retinol levels.
AB  - Retinol is one of the most biologically active forms of vitamin A and is
      hypothesized to influence a wide range of human diseases including asthma,
      cardiovascular disease, infectious diseases and cancer. We conducted a genome
      wide association study of 5006 Caucasian individuals drawn from two cohorts of
      men: the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and the
      Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial. We
      identified two independent single-nucleotide polymorphisms associated with
      circulating retinol levels, which are located near the transthyretin (TTR) and
      retinol binding protein 4 (RBP4) genes which encode major carrier proteins of
      retinol: rs1667255 (P =2.30* 10(-17)) and rs10882272 (P =6.04* 10(-12)). We
      replicated the association with rs10882272 in RBP4 in independent samples from
      the Nurses' Health Study and the Invecchiare in Chianti Study (InCHIANTI) that
      included 3792 women and 504 men (P =9.49* 10(-5)), but found no association for
      retinol with rs1667255 in TTR among women, thus suggesting evidence for gender
      dimorphism (P-interaction=1.31* 10(-5)). Discovery of common genetic variants
      associated with serum retinol levels may provide further insight into the
      contribution of retinol and other vitamin A compounds to the development of
      cancer and other complex diseases.

PMID- 21878438
TI  - The use of Hegar's dilator for finding correct planes around the uterus.
AB  - The Hegar's dilator could be used during both laparoscopic and open surgeries to
      find the correct planes to enter into either posterior or anterior fornix with
      minimal blood loss and with ease.

PMID- 21878436
TI  - A genome-wide association study identifies a region at chromosome 12 as a
      potential susceptibility locus for restenosis after percutaneous coronary
      intervention.
AB  - Percutaneous coronary intervention (PCI) has become an effective therapy to treat
      obstructive coronary artery diseases (CAD). However, one of the major drawbacks
      of PCI is the occurrence of restenosis in 5-25% of all initially treated
      patients. Restenosis is defined as the re-narrowing of the lumen of the blood
      vessel, resulting in renewed symptoms and the need for repeated intervention. To
      identify genetic variants that are associated with restenosis, a genome-wide
      association study (GWAS) was conducted in 295 patients who developed restenosis
      (cases) and 571 who did not (controls) from the GENetic Determinants of
      Restenosis (GENDER) study. Analysis of ~550 000 single nucleotide polymorphisms
      (SNPs) in GENDER was followed by a replication phase in three independent case
      control populations (533 cases and 3067 controls). A potential susceptibility
      locus for restenosis at chromosome 12, including rs10861032 (P(combined) = 1.11 *
      10(-7)) and rs9804922 (P(combined) = 1.45 * 10(-6)), was identified in the GWAS
      and replication phase. In addition, both SNPs were also associated with coronary
      events (rs10861032, P(additive) = 0.005; rs9804922, P(additive) = 0.023) in a
      trial based cohort set of elderly patients with (enhanced risk of) CAD (PROSPER)
      and all-cause mortality in PROSPER (rs10861032, P(additive) = 0.007; rs9804922,
      P(additive) = 0.013) and GENDER (rs10861032, P(additive) = 0.005; rs9804922,
      P(additive) = 0.023). Further analysis suggests that this locus could be involved
      in regulatory functions.

PMID- 21878440
TI  - Skeletal fluorosis mimicking seronegative spondyloarthropathy: a deceptive
      presentation.
AB  - Skeletal fluorosis is rarely recognized early and is a major cause of morbidity.
      We report on a 40-year-old man with skeletal fluorosis mimicking seronegative
      spondyloarthropathy.

PMID- 21878439
TI  - Treatment protocol and relapses of brucella endocarditis; cotrimoxazole in
      combination with the treatment of brucella endocarditis.
AB  - Antibiotic treatment, surgical intervention and postoperative antibiotic regimens
      are recommended for the treatment of brucella endocarditis (BE). Our clinical
      antibiotic regimens involve a triple antibiotic regimen for treating BE before
      the operation. The combination of three antibiotics is continued for at least six
      months and until the titres of the Wright serologic test are diminished to 1:160
      levels. In this study, our aim was to evaluate the effects of combined medical
      and surgical treatments on survival and relapse rates in the periods of mid to
      late terms. We investigated 13 patients who were treated between January 1993 and
      June 2009. Our clinical observations led us to use a combination of rifampicin
      (900 mg twice a day), streptomycin (12 to 16 mg/kg/24 h intramuscularly) and
      doxycycline (200 mg/kg twice a day); rifampicin, tetracycline (8 mg/kg three
      times a day) and cotrimoxazole (15 mg/kg twice a day) or rifampicin, doxycycline
      and cotrimoxazole regimen for treating BE before the operation. This treatment
      should be continued for at least six months after surgery in order to prevent
      relapses.

PMID- 21878441
TI  - Prevalence of Nocardia species among HIV-positive patients with suspected
      tuberculosis.
AB  - The objective of the study was to determine the frequency of nocardiosis in HIV
      positive and HIV-negative individuals clinically suspected of having tuberculosis
      (TB). The study population (n = 171) were those who attended chest hospitals in
      Khartoum State, Sudan, between January and March 2010. The patients suffered from
      pulmonary infections with positive acid-fast bacilli. Blood (n = 171) and sputum
      (n = 171) samples were collected simultaneously. Blood samples were tested
      serologically for the presence of antibodies using HIV/Intensified Combination
      Prevention (ICP) test and sputum were cultured onto Lowenstein Jensen slants
      according to standard methods. Isolates showing rapid growth characteristic of
      Nocardiae were subcultured and subsequently identified using glucose yeast
      extract agar medium. All candidates in the study population (n = 171) suffered
      from pulmonary infections, nocardiosis was diagnosed in 4% (n = 7), HIV-positive
      cases were 17 (9.9%). Five Nocardia species were isolated from HIV-negative
      patients whereas two were from HIV-positive patients. Nocardia spp. cause
      pulmonary infections (4.09%) in both immunocompetent (2.92%) as well as
      immunocompromised (1.17%) patients who attend chest clinics in Sudan.

PMID- 21878442
TI  - Clubfoot in Malawi: treatment-seeking behaviour.
AB  - We explore the treatment-seeking behaviour of guardians of patients undergoing
      treatment for clubfoot at clinics run by the Malawi National Clubfoot Programme
      (MNCP). Core data was collected and analysed using qualitative methodologies of
      critical medical anthropology. Sixty detailed case studies were completed, each
      based on an extended open-ended interview with patient guardians. Two positive
      drivers in seeking treatment for clubfoot were identified: a desire to correct
      the impairment; and a direct instruction to do so, usually from a health-care
      professional. Four main barriers prevented treatment seeking: lack of knowledge
      about the condition and its treatment; familial resistance; logistical obstacles;
      and socio-economic pressures. In delivering effective health care, organizations
      should seek to minimize barriers and their impact, whilst maximizing drivers that
      lead to positive action.

PMID- 21878434
TI  - RUBY-1: a randomized, double-blind, placebo-controlled trial of the safety and
      tolerability of the novel oral factor Xa inhibitor darexaban (YM150) following
      acute coronary syndrome.
AB  - AIMS: To establish the safety, tolerability and most promising regimen of
      darexaban (YM150), a novel, oral, direct factor Xa inhibitor, for prevention of
      ischaemic events in acute coronary syndrome (ACS). METHODS: In a 26-week, multi
      centre, double-blind, randomized, parallel-group study, 1279 patients with recent
      high-risk non-ST-segment or ST-segment elevation ACS received one of six
      darexaban regimens: 5 mg b.i.d., 10 mg o.d., 15 mg b.i.d., 30 mg o.d., 30 mg
      b.i.d., or 60 mg o.d. or placebo, on top of dual antiplatelet treatment. Primary
      outcome was incidence of major or clinically relevant non-major bleeding events.
      The main efficacy outcome was a composite of death, stroke, myocardial
      infarction, systemic thromboembolism, and severe recurrent ischaemia. RESULTS:
      Bleeding rates were numerically higher in all darexaban arms vs. placebo (pooled
      HR: 2.275; 95% CI: 1.13-4.60, P = 0.022). Using placebo as reference (bleeding
      rate 3.1%), there was a dose-response relationship (P = 0.009) for increased
      bleeding with increasing darexaban dose (6.2, 6.5, and 9.3% for 10, 30, and 60 mg
      daily, respectively), which was statistically significant for 30 mg b.i.d. (P =
      0.002). There was no decrease (indeed a numerical increase in the 30 and 60 mg
      dose arms) in efficacy event rates with darexaban, but the study was underpowered
      for efficacy. Darexaban showed good tolerability without signs of liver toxicity.
      CONCLUSIONS: Darexaban when added to dual antiplatelet therapy after ACS produces
      an expected dose-related two- to four-fold increase in bleeding, with no other
      safety concerns but no signal of efficacy. Establishing the potential of low-dose
      darexaban in preventing major cardiac events after ACS requires a large phase III
      trial. ClinicalTrials.gov Identifier: NCT00994292.

PMID- 21878443
TI  - Co-existence of micronutrient deficiencies in hospitalized children with severe
      malnutrition treated according to the WHO protocol.
AB  - We assessed the involvement of vitamin A deficiency (VAD) and anaemia as co
      morbidities associated with severe forms of protein-energy malnutrition in
      hospitalized children. In a descriptive case series study of 57 children, one
      clinical case of xerophthalmia was diagnosed: 44.0% had levels of serum retinol
      <20 ug/dL and 88.0% had Hb <11 g/dL, of whom 30.0% had haemoglobin levels below
      7.0 g/dL.

PMID- 21878444
TI  - Making the most of evaluation: a mixed methods study in the English NHS.
AB  - OBJECTIVES: To increase understanding about how evaluations of health policy
      initiatives are commissioned, conducted and used. METHODS: A mapping exercise was
      conducted to identify evaluation of initiatives promoted by the White Paper 'Our
      health, our care, our say' in the English NHS. All evaluations were subjected to
      critical appraisal and 21 were purposively selected as case studies, involving
      documentary analysis and 60 interviews with those commissioning, conducting and
      affected by the evaluation. RESULTS: Variation in the types of evaluation being
      undertaken did not reflect the importance of the initiatives being evaluated.
      Most evaluations collected evidence about uptake, processes of care and users'
      perceptions. While some provided useful information about how initiatives could
      be improved, few provided robust evidence about the benefits or costs of the
      initiatives. Those who commissioned evaluations had similar concerns to those who
      conducted them. There was a commitment to the concept of evaluation but little
      clarity about how findings would be used. Evaluation was often commissioned too
      late to influence decisions about implementation. Compromises over research
      design and difficulties collecting data limited the potential to provide robust
      evidence about benefits. There were tensions between the desire of evaluators for
      methodological rigour and the needs of service providers for swift, contextually
      relevant findings. There were concerns about the transparency of methods and
      results. CONCLUSIONS: Considerable public resources are committed to evaluation,
      but this investment is less productive than it could be. This article specifies
      several ways in which the use of evaluation of initiatives in health and social
      care could be improved.

PMID- 21878445
TI  - Secondary use of randomized controlled trials to evaluate drug safety: a review
      of methodological considerations.
AB  - BACKGROUND: Randomized clinical trials (RCTs) are often positioned at the top of
      evidence hierarchies. Meta-analyses of RCTs aim to integrate the state of
      knowledge on a given scientific question, particularly for rare drug-related
      outcomes. However, although RCTs are valuable tools in our armamentarium, they
      are rarely designed to evaluate drug safety and are thus susceptible to
      limitations that may hamper the ability of both RCTs and meta-analyses to fully
      characterize the safety profiles of drugs. Their potential limitations might be
      exacerbated in the study of rare outcomes, often encountered in drug safety
      assessment, when even minor deviations from the intended randomization could
      impact the stability of the risk estimates. PURPOSE: This article considers the
      methodological caveats of both RCTs and meta-analyses of RCTs pertinent to the
      study of drug-related harms. It is intended to stimulate discussion about the
      impact of these caveats on interpreting findings of RCTs and meta-analyses for
      drug safety, which would foster more robust, critical evaluations, and thus
      enhance clinical and regulatory decision-making. METHODS: Pertinent issues that
      can influence the interpretation of drug-related harms discussed in this article
      were based on authors' expertise and review of the literature. RESULTS:
      Investigators and clinicians should be cognizant of the potential limitations of
      the secondary use of RCTs and meta-analyses in the assessment of drug-related
      harms and, when applicable, should consider potential remedies to overcome these
      limitations. LIMITATIONS: Only few practical examples are included in the article
      due to the fact that many of the discussed caveats are not examined and/or
      reported in many publications. In addition, the confidential nature of data
      reviewed at a regulatory agency forestalls an in depth discussion of examples
      pertaining to specific drugs. Furthermore, our ability to quantify the extent of
      encountering, or the actual impact of, the caveats addressed in this review on
      the RCTs findings is limited. It is worth noting that the mere encounter of a
      given caveat does not mean that it will obviate the utility of drug safety
      information from a given trial. The extent of its impact is expected to vary
      based on the specifics of the trial, the drugs studied, the indications, and the
      nature of the adverse events. CONCLUSIONS: Although some of the limitations
      described are inherent in RCTs, some of the sources of bias highlighted in this
      article could be minimized by careful RCT design, planned follow-up, and improved
      collection of information on adverse events. As future research sheds more light
      on pertinent knowledge gaps and issues, the ability to maximize the use of RCTs
      and meta-analyses of RCTs to address drug safety questions of interest will be
      greatly enhanced.

PMID- 21878446
TI  - Bayesian approaches for comparative effectiveness research.
AB  - BACKGROUND: A hallmark of comparative effectiveness research is the analysis of
      all the available evidence from different studies addressing a given question of
      medical risk versus benefit. The Bayesian statistical approach is ideally suited
      for such investigations because it is inherently synthetic and because it is
      philosophically uninhibited regarding the ability to analyze all the available
      evidence. PURPOSE: To consider a variety of comparative effectiveness research
      settings and show how the Bayesian approach applies. METHODS: The Bayesian
      approach is described as it has been applied to the comparative analysis of
      implantable cardioverter defibrillators and mammographic screening, in the Cancer
      Intervention and Surveillance Modeling Network, in comparisons of patient
      outcomes data from different sources, and in designing adaptive clinical trials
      to support the development of 'personalized medicine.' RESULTS: Bayesian methods
      allow for continued learning as data accrue and for cumulating meta-analyses and
      the comparison of heterogeneous studies. Bayesian methods enable predictive
      probability distributions of the results of future studies. LIMITATIONS: Bayesian
      posterior distributions are subject to potential bias - in the selection of
      'available' evidence and in the choice of a likelihood model. Sensitivity
      analyses help to control this bias. CONCLUSIONS: The Bayesian approach has much
      to offer comparative effectiveness research. It provides a mechanism for
      synthesizing various sources of information and for updating knowledge in an
      online fashion as evidence accumulates.

PMID- 21878447
TI  - Challenges to accrual predictions to phase III cancer clinical trials: a survey
      of study chairs and lead statisticians of 248 NCI-sponsored trials.
AB  - BACKGROUND: Research on barriers to accrual has typically emphasized factors
      influencing participation after trial activation. PURPOSE: We sought to identify
      factors influencing trial design and accrual predictions prior to trial
      activation associated with sufficient accrual. METHODS: A 30-question web-based
      survey was sent to the study chair and lead statistician for all 248 phase III
      trials open in 1993-2002 by five Clinical Trials Cooperative Groups. Questions
      addressed prior trial experience, trial design elements, accrual predictions, and
      perceived accrual influences. Accrual sufficiency categorization was derived from
      Clinical Trials Cooperative Group records: sufficient accrual included trials
      closed with complete accrual or at interim analysis, insufficient accrual
      included trials closed with inadequate accrual. Responses were analyzed by
      respondent role (study chair/lead statistician) and accrual sufficiency. RESULTS:
      Three hundred and nine eligible responses were included (response rate, 63%; lead
      statisticians, 81%; and study chairs, 45%), representing trials with sufficient
      (63%) and insufficient accruals (37%). Study chair seniority or lead statistician
      experience was not linked to accrual sufficiency. Literature review, study
      chair's personal experience, and expert opinion within Clinical Trials
      Cooperative Group most commonly influenced control arm selection. Clinical Trials
      Cooperative Group experience most influenced accrual predictions. These
      influences were not associated with accrual sufficiency. Among respondents citing
      accrual difficulties (41%), factors negatively influencing accrual were not
      consistently identified. Respondents credited three factors with positively
      influencing accrual: clinical relevance of study, lack of competing trials, and
      protocol paralleling normal practice. LIMITATIONS: Perceptions of lead
      statisticians and study chairs may not accurately reflect accrual barriers
      encountered by participating physicians or patients. Survey responses may be
      subject to recall bias. CONCLUSION: Consistent factors explaining poor accrual
      were not identified, suggesting reasons for poor accrual are not well understood
      and warrant further study. Alternate strategies for accrual prediction are needed
      since Clinical Trials Cooperative Group experience is linked to successful and
      unsuccessful accrual.

PMID- 21878448
TI  - Prevention of diabetes and reduction in major cardiovascular events in studies of
      subjects with prediabetes: meta-analysis of randomised controlled clinical
      trials.
AB  - BACKGROUND: Impaired glucose tolerance (IGT) and impaired fasting glucose (IFG)
      are pre-diabetic states, treatment of which may prevent or delay the onset of
      overt diabetes and thus potentially reduce major cardiovascular (CV) events. We
      therefore sought to determine whether interventions (including diet, exercise and
      pharmacological therapy), altered all-cause and cardiovascular related mortality
      in such subjects. METHODS: We performed a meta-analysis of prospective,
      randomised controlled trials (RCTs) that were identified in the medical
      literature and databases. Trials were eligible for inclusion if they reported all
      cause mortality rates (at a minimum), recruited approximately 100 patients and
      had a minimum follow-up of one year. Interventions were divided into
      pharmacological and non-pharmacological. RESULTS: Ten RCTs that enrolled 23,152
      patients met the above entry criteria. Trials ran for an average of 3.75 years.
      Diabetes was delayed or prevented by these interventions vs control (risk ratio
      0.83, 95%CI 0.80-0.86). Non-drug approaches (n = 3495) were superior to drug
      based approaches (n = 20,872) in diabetes prevention (0.52, 0.46-0.58 vs 0.70,
      0.58-0.85, P < 0.05). There was no difference in risk of all-cause mortality in
      the intervention versus control group (0.96, 0.84-1.10) and no difference in CV
      death (1.04, 0.61-1.78). There was a non-significant trend towards reduction in
      fatal and non-fatal myocardial infarction (0.59, 0.23-1.50). Fatal and non-fatal
      stroke was borderline reduced (0.76, 0.58-0.99) with intervention versus control.
      CONCLUSIONS: Despite interventions being mostly successful in retarding
      progression to overt diabetes, this did not result in reductions in all-cause or
      cardiovascular mortality, or myocardial infarction, with the possible exception
      of stroke.

PMID- 21878449
TI  - Deterioration of glomerular endothelial surface layer and the alteration in the
      renal function after a growth promoter boldenone injection in rabbits.
AB  - Boldenone is an anabolic steroid developed for veterinary use. Recently, it is
      used by bodybuilders in both off-season and precontest, where it is well known
      for increasing vascularity while preparing for a bodybuilding contest. However,
      the side effect of this steroid on the human health is still unclear. Therefore,
      the present study was designed to investigate the possible effect of the growth
      promoter, boldenone undecylenate, on the function and structure of the rabbit's
      kidneys. A total of 36 adult New Zealand rabbits were divided into 4 groups.
      Control group includes animals that were injected intramuscularly with olive oil
      and dissected after 3 weeks. Three experimental groups include animals that
      receive one, two and three intramuscular injections of 5 mg/kg body weight
      boldenone, and dissected after 3, 6, and 9 weeks, respectively, and the interval
      of each dose of boldenone was 3 weeks. The biochemical analysis of the blood
      serum of treated rabbit showed a significant increase in the total protein, urea
      and creatinine concentrations, with a significant decrease in albumin/globulin
      (A/G) ratio. At the same time, a significant glomerulus mass reduction that
      accompanied with the expression of CD34, a marker for endothelial cells
      deterioration, was also determined. The incidence of the glomerulosclerosis was
      significantly increased compared with the control group (0.46 +/- 0.05, p <
      0.05). The glomerulosclerosis scores were 1.32 +/- 0.10, 2.14 +/- 0.11 and 3.02
      +/- 0.09 in groups 2, 3 and 4, respectively. These findings suggest that misuse
      of the boldenone undecylenate may contribute to the occurrence of a chronic renal
      injury that may lead to a progressive renal failure.

PMID- 21878450
TI  - Effect of acrylamide on some hormones and endocrine tissues in male rats.
AB  - Acrylamide is oxidized by cytochrome P450 2E1 (CYP2E1) to its epoxide form,
      glycidamide, which is believed to be responsible for the mutagenic and
      carcinogenic activities. This study was carried out to investigate the early
      changes that may be related to the carcinogenic activity of acrylamide in
      thyroid, adrenal glands and testis in male rats. Forty adult Sprague Dawley male
      rats were divided equally into four groups, rats of Group I served as control,
      and rats of Groups II, III and IV were treated orally with acrylamide with doses
      5, 10, 15 mg/kg/day body weight for 8 weeks. The results indicated that the
      plasma carcino embryonic antigen (CEA) and malondialdehyde (MDA) levels are
      higher, but free and total testosterone, triiodothyronine (T(3)) and thyroxine,
      or 3,5,3',5'-tetraiodothyronine (T(4)) and corticosterone levels are lower in
      rats treated with acrylamide than that in control rats. This study provides
      evidence of endocrine disturbance to the testis, thyroid and adrenal glands,
      which are also the organs in which acrylamide has been shown to cause tumors in
      experimental animals.

PMID- 21878451
TI  - Brain lesion location and clinical status 20 years after a diagnosis of
      clinically isolated syndrome suggestive of multiple sclerosis.
AB  - BACKGROUND/OBJECTIVES: The objective of this study was to investigate
      associations between the spatial distribution of brain lesions and clinical
      outcomes in a cohort of people followed up 20 years after presentation with a
      clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS).
      METHODS: Brain lesion probability maps (LPMs) of T1 and T2 lesions were generated
      from 74 people who underwent magnetic resonance imaging (MRI) and clinical
      assessment a mean of 19.9 years following a CIS. One-tailed t-test statistics
      were used to compare LPMs between the following groups: clinically definite (CD)
      MS and those who remained with CIS, with an abnormal MRI; people with MS and an
      Expanded Disability Status Scale (EDSS) <=3 and >3; people with relapsing
      remitting (RR) and secondary progressive (SP) MS. The probability of each voxel
      being lesional was analysed adjusting for age and gender using a multiple linear
      regression model. RESULTS: People with CDMS were significantly more likely than
      those with CIS and abnormal scan 20 years after onset to have T1 and T2 lesions
      in the corona radiata, optic radiation, and splenium of the corpus callosum
      (periventricularly) and T2 lesions in the right fronto-occipital fasciculus.
      People with MS EDSS >3, compared with those with EDSS <=3, were more likely to
      have optic radiation and left internal capsule T2 lesions. No significant
      difference in lesion distribution was noted between RRMS and SPMS. CONCLUSION:
      This work demonstrates that lesion location characteristics are associated with
      CDMS and disability after long-term follow-up following a CIS. The lack of lesion
      spatial distribution differences between RRMS and SPMS suggests focal pathology
      affects similar regions in both subgroups.

PMID- 21878452
TI  - Multiple sclerosis prevalence in Malaga, Southern Spain estimated by the capture
      recapture method.
AB  - BACKGROUND: Although not definitively proven, there is commonly accepted to be a
      latitudinal gradient in the distribution of multiple sclerosis (MS), which is
      more frequent in temperate zones. The European Mediterranean countries are
      situated in a zone of median frequency, although ever increasing figures have
      been noted in the last decades. OBJECTIVE: The objective of this study was to
      assess the current prevalence rate of MS in the province of Malaga, Southern
      Spain. METHODS: The capture-recapture method (CRM) uses independent sources of
      data and permits the number of non-registered cases of a given disease to be
      estimated, and by doing so, to avoid ascertainment bias. RESULTS: Use of this
      method showed the estimated prevalence rate of MS in the province of Malaga,
      Southern Spain, to be 125/10(5) (95% confidence interval: 102/10(5)-169/10(5)),
      higher than the figures published previously. CONCLUSIONS: Although we recognize
      that these data need to be confirmed in further studies and in other areas of the
      country using a similar method, we believe this study is the first to find such
      high figure of prevalence, being very similar to the figures reported in recent
      years in other southern European countries.

PMID- 21878453
TI  - Methylation-dependent PAD2 upregulation in multiple sclerosis peripheral blood.
AB  - BACKGROUND: Peptidylarginine deiminase 2 (PAD2) and peptidylarginine deiminase 4
      (PAD4) are two members of PAD family which are over-expressed in the multiple
      sclerosis (MS) brain. Through its enzymatic activity PAD2 converts myelin basic
      protein (MBP) arginines into citrullines - an event that may favour autoimmunity 
      while peptidylarginine deiminase 4 (PAD4) is involved in chromatin remodelling.
      OBJECTIVES: Our aim was to verify whether an altered epigenetic control of PAD2,
      as already shown in the MS brain, can be observed in peripheral blood mononuclear
      cells (PBMCs) of patients with MS since some of these cells also synthesize MBP.
      METHODS: The expression of most suitable reference genes and of PAD2 and PAD4 was
      assessed by qPCR. Analysis of DNA methylation was performed by bisulfite method.
      RESULTS: The comparison of PAD2 expression level in PBMCs from patients with MS
      vs. healthy donors showed that, as well as in the white matter of MS patients,
      the enzyme is significantly upregulated in affected subjects. Methylation pattern
      analysis of a CpG island located in the PAD2 promoter showed that over-expression
      is associated with promoter demethylation. CONCLUSION: Defective regulation of
      PAD2 in the periphery, without the immunological shelter of the blood-brain
      barrier, may contribute to the development of the autoimmune responses in MS.

PMID- 21878454
TI  - A placebo-controlled, parallel-group, randomized withdrawal study of subjects
      with symptoms of spasticity due to multiple sclerosis who are receiving long-term
      Sativex(r) (nabiximols).
AB  - BACKGROUND: Open-label studies are not ideal for providing robust evidence for
      long-term maintenance of efficacy of medicines, especially where medicines
      provide symptom relief and where long-term use of a placebo may be problematic
      and not ethical. OBJECTIVE: To evaluate the maintenance of efficacy of Sativex in
      subjects who have gained long-term symptomatic relief of spasticity in multiple
      sclerosis (MS), and to assess the impact of sudden medicine withdrawal. METHODS:
      An enriched enrolment randomized withdrawal study design was used. Eligible
      subjects with ongoing benefit from Sativex for at least 12 weeks entered this 5
      week placebo-controlled, parallel-group, randomized withdrawal study. Each
      subjects' previous effective and tolerated dose was continued. RESULTS: A total
      of 18 subjects per group were enrolled. Demographics showed a mean duration of MS
      of 16.4 years, spasticity 12.7 years, mean duration of Sativex use of 3.6 years
      (median 3.4 years) and a mean daily dose of 8.25 sprays. Primary outcome of time
      to treatment failure was significantly in favour of Sativex (p = 0.013).
      Secondary endpoints showed significant changes in the Carer and Subject's Global
      Impression of Change scales in favour of Sativex. CONCLUSIONS: Maintenance of
      Sativex efficacy in long-term symptomatic improvement of spasticity to a group of
      subjects with MS has been confirmed using this study design.

PMID- 21878455
TI  - Effect of BG-12 on contrast-enhanced lesions in patients with relapsing-
      remitting multiple sclerosis: subgroup analyses from the phase 2b study.
AB  - BACKGROUND: In a phase 2b study in patients with relapsing-remitting MS (RRMS),
      BG-12 240 mg three times daily significantly reduced the number of new gadolinium
      enhanced (Gd+) lesions from weeks 12 to 24 (primary end point) by 69% compared
      with placebo. OBJECTIVE: In this analysis, the effect of BG-12 240 mg three times
      daily on the number of Gd+ lesions from weeks 12 to 24 was evaluated in subgroups
      based on baseline disease characteristics and demographics. METHODS: Two hundred
      and fifty-seven patients were randomized equally to receive BG-12 (120 mg once
      daily or three times daily or 240 mg three times daily) or placebo. RESULTS: BG
      12 240 mg three times daily significantly reduced the number of new Gd+ lesions
      compared with placebo in the following subgroups: Expanded Disability Status
      Scale (EDSS) score <= 2.5 (74%), EDSS score > 2.5 (63%), no Gd+ lesions (80%), >=
      1 Gd+ lesion (55%), age < 40 years (49%), age >= 40 years (89%), female patients
      (81%), disease duration <= 6 years (81%) and disease duration > 6 years (54%)
      (all comparisons p < 0.05). CONCLUSION: BG-12 demonstrated efficacy in patients
      with RRMS by decreasing new Gd+ lesion development across a range of subgroups
      defined by baseline disease characteristics or demographics.

PMID- 21878457
TI  - From immunological tolerance to stem cell therapy and back: an interview with
      Irving Weissman. Interview by Sarah Allan.

PMID- 21878458
TI  - Newly identified aspects of tumor suppression by RB.
AB  - The retinoblastoma (RB) tumor suppressor belongs to a cellular pathway that plays
      a crucial role in restricting the G1-S transition of the cell cycle in response
      to a large number of extracellular and intracellular cues. Research in the last
      decade has highlighted the complexity of regulatory networks that ensure proper
      cell cycle progression, and has also identified multiple cellular functions
      beyond cell cycle regulation for RB and its two family members, p107 and p130.
      Here we review some of the recent evidence pointing to a role of RB as a
      molecular adaptor at the crossroads of multiple pathways, ensuring cellular
      homeostasis in different contexts. In particular, we discuss the pro- and anti
      tumorigenic roles of RB during the early stages of cancer, as well as the
      importance of the RB pathway in stem cells and cell fate decisions.

PMID- 21878460
TI  - On the power of the Cochran-Armitage test for trend in the presence of
      misclassification.
AB  - The Cochran-Armitage (CA) test is commonly used in both epidemiology and genetics
      to test for linear trend in two-way tables with a binary outcome. There has been
      increasing interest in the power and size of the test and in determination of
      sample size, especially when there is potential misclassification in the
      'exposure' category. This article provides a unified approach to determination of
      the power function over different sampling strategies (fixed overall sample size
      or fixed marginal sample sizes) and allowing for misclassification in one or both
      variables. The misclassification may be either differential or non-differential.
      In addition to the standard CA test, results are also given which provide some
      insight into the performance of the modified CA test, which utilizes a standard
      error obtained without invoking the null hypothesis. Even without
      misclassification, some new expressions are also obtained for determining power
      with a fixed overall sample size. Numerical illustrations are presented with an
      emphasis on the more commonly occurring problem of misclassification in the
      exposure category.

PMID- 21878461
TI  - Disproportionality methods for pharmacovigilance in longitudinal observational
      databases.
AB  - Data mining disproportionality methods (PRR, ROR, EBGM, IC, etc.) are commonly
      used to identify drug safety signals in spontaneous report system (SRS)
      databases. Newer data sources such as longitudinal observational databases (LOD)
      provide time-stamped patient-level information and overcome some of the SRS
      limitations such as an absence of the denominator, total number of patients who
      consume a drug, and limited temporal information. Application of the
      disproportionality methods to LODs has not been widely explored. The scale of the
      LOD data provides an interesting computational challenge. Larger health claims
      databases contain information on more than 50 million patients and each patient
      has records for up to 10 years. In this article we systematically explore the
      application of commonly used disproportionality methods to simulated and real LOD
      data.

PMID- 21878459
TI  - Down syndrome: searching for the genetic culprits.
AB  - Down syndrome (DS) is caused by trisomy of human chromosome 21 (Hsa21) and
      results in a large number of phenotypes, including learning difficulties, cardiac
      defects, distinguishing facial features and leukaemia. These are likely to result
      from an increased dosage of one or more of the ~310 genes present on Hsa21. The
      identification of these dosage-sensitive genes has become a major focus in DS
      research because it is essential for a full understanding of the molecular
      mechanisms underlying pathology, and might eventually lead to more effective
      therapy. The search for these dosage-sensitive genes is being carried out using
      both human and mouse genetics. Studies of humans with partial trisomy of Hsa21
      have identified regions of this chromosome that contribute to different
      phenotypes. In addition, novel engineered mouse models are being used to map the
      location of dosage-sensitive genes, which, in a few cases, has led to the
      identification of individual genes that are causative for certain phenotypes.
      These studies have revealed a complex genetic interplay, showing that the diverse
      DS phenotypes are likely to be caused by increased copies of many genes, with
      individual genes contributing in different proportions to the variance in
      different aspects of the pathology.

PMID- 21878462
TI  - Multiplicity of data in trial reports and the reliability of meta-analyses:
      empirical study.
AB  - OBJECTIVES: To examine the extent of multiplicity of data in trial reports and to
      assess the impact of multiplicity on meta-analysis results. DESIGN: Empirical
      study on a cohort of Cochrane systematic reviews. DATA SOURCES: All Cochrane
      systematic reviews published from issue 3 in 2006 to issue 2 in 2007 that
      presented a result as a standardised mean difference (SMD). We retrieved trial
      reports contributing to the first SMD result in each review, and downloaded
      review protocols. We used these SMDs to identify a specific outcome for each meta
      analysis from its protocol. Review methods Reviews were eligible if SMD results
      were based on two to ten randomised trials and if protocols described the
      outcome. We excluded reviews if they only presented results of subgroup analyses.
      Based on review protocols and index outcomes, two observers independently
      extracted the data necessary to calculate SMDs from the original trial reports
      for any intervention group, time point, or outcome measure compatible with the
      protocol. From the extracted data, we used Monte Carlo simulations to calculate
      all possible SMDs for every meta-analysis. RESULTS: We identified 19 eligible
      meta-analyses (including 83 trials). Published review protocols often lacked
      information about which data to choose. Twenty-four (29%) trials reported data
      for multiple intervention groups, 30 (36%) reported data for multiple time
      points, and 29 (35%) reported the index outcome measured on multiple scales. In
      18 meta-analyses, we found multiplicity of data in at least one trial report; the
      median difference between the smallest and largest SMD results within a meta
      analysis was 0.40 standard deviation units (range 0.04 to 0.91). CONCLUSIONS:
      Multiplicity of data can affect the findings of systematic reviews and meta
      analyses. To reduce the risk of bias, reviews and meta-analyses should comply
      with prespecified protocols that clearly identify time points, intervention
      groups, and scales of interest.

PMID- 21878463
TI  - Medtronic submits full data on spinal protein to independent scrutiny.

PMID- 21878464
TI  - Extent and determinants of patients' unvoiced needs.
AB  - Patients with issues or health problems usually plan to discuss their concerns
      with their health care providers. If these concerns were not presented or voiced
      during the health care provider-patient encounter, the patients are considered to
      have unvoiced needs. This article examines the extent and possible determinants
      of patients' unvoiced needs in an outpatient setting. A cross-sectional study was
      conducted in 5 Ministry of Health Malaysia primary health facilities throughout
      the country. Of 1829 who participated, 5 did not respond to the question on
      planned issues. Of the 1824 respondents, 57.9% (95% confidence interval = 47.1
      68.7) claimed to have issues/problems they planned to share, of whom 15.1% to
      26.7% had unvoiced needs. Extent of unvoiced needs differed by employment status,
      perceived category of health care provider, and study center. Perceived category
      of health care provider, method of questionnaire administration, and study center
      were the only significant determinants of unvoiced needs. Unvoiced needs do exist
      in Malaysia and there is a need for health care providers to be aware and take
      steps to counter this.

PMID- 21878465
TI  - The effects of office ergonomic training on musculoskeletal complaints, sickness
      absence, and psychological well-being: a cluster randomized control trial.
AB  - This study explored whether musculoskeletal complaints can be reduced by the
      provision of ergonomics education. A cluster randomized controlled trial study
      was conducted in which 3 units were randomized to intervention and received
      training and 3 units were given a leaflet. The effect of intervention on
      knowledge, workstation practices, musculoskeletal complaints, sickness absence,
      and psychological well-being were assessed at 6 and 12 months. Although there was
      no increment of knowledge among workers, significant improvements in workstation
      practices in the use of monitor, keyboard, and chair were observed. There were
      significant reductions in neck and upper and lower back complaints among workers
      but these did not translate into fewer days lost from work. Workers' stress was
      found to be significantly reduced across the studies. In conclusion, office
      ergonomics training can be beneficial in reducing musculoskeletal risks and
      stress among workers. 

PMID- 21878466
TI  - Personal maternal care reflections of general practice physicians.
AB  - BACKGROUND: As the number of female GPs increases, the need to understand
      delivery of maternity care to this group becomes increasingly important. Previous
      literature suggests doctors face additional barriers in utilizing health care
      compared to other patients, but little is known about GPs' maternal health care
      experiences and whether their occupation facilitates or compromises care.
      OBJECTIVE: To explore female GPs' personal experiences of maternal health care
      and how occupation affects care received. METHODS: Female GPs with children aged
      6 months to 5 years were recruited from South Birmingham Primary Care Trust with
      subsequent snowballing. Data were obtained using semi-structured interviews and
      constant comparison analysis was applied to develop themes and categories.
      RESULTS: Fourteen GPs participated and no new themes emerged after interview 10
      suggesting data saturation was achieved. Overall, GPs felt they received better
      care due to their occupation and where established relationships between the GP
      and the health care professional existed, communication and care satisfaction was
      enhanced. However, assumptions about knowledge led to reduced information
      provision and some problems in care provision, especially during labour and early
      motherhood when women were most vulnerable and unable to rely on work skills to
      address information deficits. CONCLUSION: This research supports the growing body
      of evidence that there are unique problems facing doctor-patients and clinicians
      treating them. However, contrary to expectations derived from anecdotal evidence,
      GPs indicated that care was enhanced due to their occupation. This study raises
      awareness of areas for consideration when female GPs approach pregnancy and
      health care professionals deliver maternal health care.

PMID- 21878467
TI  - Routinely recorded patient safety events in primary care: a literature review.
AB  - BACKGROUND: Existing patient-level data can be used to measure and monitor
      patient safety. Data from sources including electronic patient records are
      routinely collected in primary care and may be suitable for adverse event
      screening, such as patient safety indicators. To inform the feasibility of
      developing primary care measures of patient harm, information about routinely
      collected data is needed. OBJECTIVE: A literature review was conducted to
      determine the types of adverse events that are routinely recorded in primary
      care. METHODS: We searched ASSIA, Cochrane Library, Embase, HMIC, ISI Web of
      Science, Medline and PsycInfo databases, grey literature and websites. We
      included only original research studies in English where routinely collected
      patient data were used to identify adverse events occurring in primary or
      ambulatory care settings. Adverse events were defined as unexpected and
      undesirable patient outcomes arising from health care contact. RESULTS: Of 5029
      citations identified, 15 were reviewed. Twelve studies used multiple data
      sources. Approximately 6.5% of adult emergency admissions were due to drug
      related events (n = 1225). Between 0.7% and 2.3% of deaths following adverse
      events were attributed to treatment in primary care. A large proportion of
      adverse events resulting in the most severe harm may be preventable. For example,
      one study estimated that 42% of serious adverse drug events were avoidable.
      CONCLUSIONS: There is limited use of routinely collected data to measure adverse
      events in primary care despite large volumes of data generated. The potential for
      using readily available data recorded in primary care for active patient safety
      surveillance needs further exploration.

PMID- 21878468
TI  - Perceptions of quality of life and disability in homeless persons with
      schizophrenia and persons with schizophrenia living in non-institutional housing.
AB  - BACKGROUND: Homelessness is common in persons with schizophrenia. It is unclear
      how housing conditions and homelessness affect their quality of life and their
      disability. AIMS: To explore the self-perceived quality of life and disability of
      homeless persons with schizophrenia and of those of persons with schizophrenia
      living in non-institutional housing. METHODS: Seventy-six not-homeless and 50
      homeless persons with schizophrenia were assessed using the World Health
      Organization's Quality of Life - short version (WHOQOL-Bref) and Disability
      Assessment Schedule (WHODAS-II). Univariate comparisons of the two groups were
      made for sociodemographic variables, clinical characteristics, perceived quality
      of life and disability. A regression model was used to adjust for potential
      confounding factors between quality of life, disability and housing. RESULTS:
      After controlling for age, gender, marital status and age of first hospital
      admission, homeless persons had more positive scores for the quality of life
      domain 'health', for the disability domain 'getting along with people' and for
      the total disability score than persons in non-institutional housing. CONCLUSION:
      Contrary to our expectations, the persons in non-institutional housing reported a
      lower quality of life and more disability than the homeless people. Future
      research should clarify whether non-institutional housing in and of itself can
      improve the well-being of people with schizophrenia.

PMID- 21878469
TI  - Jail and prison overcrowding and rehabilitative justice programs.

PMID- 21878470
TI  - Effect of DISC1 on the P300 waveform in psychosis.
AB  - INTRODUCTION: Abnormalities in the neurophysiological measures P300 amplitude and
      latency constitute endophenotypes for psychosis. Disrupted-in-Schizophrenia-1
      (DISC1) has been proposed as a promising susceptibility gene for schizophrenia,
      and a previous study has suggested that it is associated with P300 deficits in
      schizophrenia. METHODS: We examined the role of variation in DISC1 polymorphisms
      on the P300 endophenotype in a large sample of patients with schizophrenia or
      psychotic bipolar disorder (n = 149), their unaffected relatives (n = 130), and
      unrelated healthy controls (n = 208) using linear regression and haplotype
      analysis. RESULTS: Significant associations between P300 amplitude and latency
      and DISC1 polymorphisms/haplotypes were found. Those homozygous for the A allele
      of single-nucleotide polymorphism (SNP) rs821597 displayed significantly reduced
      P300 amplitudes in comparison with homozygous for the G allele (P = .009) and the
      heterozygous group (P = .018). Haplotype analysis showed a significant
      association for DISC1 haplotypes
      (rs3738401|rs6675281|rs821597|rs821616|rs967244|rs980989) and P300 latency.
      Haplotype GCGTCG and ACGTTT were associated with shorter latencies. DISCUSSION:
      The P300 waveform appears to be modulated by variation in individual SNPs and
      haplotypes of DISC1. Because DISC1 is involved in neurodevelopment, one
      hypothesis is that disruption in neural connectivity impairs cognitive processes
      illustrated by P300 deficits observed in this sample.

PMID- 21878472
TI  - Primary renal MALT lymphoma presenting with cryoglobulinaemia.
AB  - Primary renal lymphoma is a rare clinicopathologic entity that typically presents
      as renal mass or renal impairment with enlarged kidneys. We describe the case of
      a 66-year-old woman who presented with type II mixed cryoglobulinaemic vasculitis
      as the first manifestation of underlying low-grade primary renal lymphoma.

PMID- 21878471
TI  - Phylogeny estimation of the radiation of western North American chipmunks
      (Tamias) in the face of introgression using reproductive protein genes.
AB  - The causes and consequences of rapid radiations are major unresolved issues in
      evolutionary biology. This is in part because phylogeny estimation is confounded
      by processes such as stochastic lineage sorting and hybridization. Because these
      processes are expected to be heterogeneous across the genome, comparison among
      marker classes may provide a means of disentangling these elements. Here we use
      introns from nuclear-encoded reproductive protein genes expected to be resistant
      to introgression to estimate the phylogeny of the western chipmunks (Tamias:
      subgenus: Neotamias), a rapid radiation that has experienced introgressive
      hybridization of mitochondrial DNA (mtDNA). We analyze the nuclear loci using
      coalescent-based species-tree estimation methods and concatenation to estimate a
      species tree and we use parametric bootstraps and coalescent simulations to
      differentiate between phylogenetic error, coalescent stochasticity and
      introgressive hybridization. Results indicate that the mtDNA gene tree reflects
      several introgression events that have occurred between taxa of varying levels of
      divergence and at different time points in the tree. T. panamintinus and T.
      speciosus appear to be fixed for ancient mitochondrial introgressions from T.
      minimus. A southern Rocky Mountains clade appears well sorted (i.e., species are
      largely monophyletic) at multiple nuclear loci, while five of six taxa are
      nonmonophyletic based on cytochrome b. Our simulations reject phylogenetic error
      and coalescent stochasticity as causes. The results represent an advance in our
      understanding of the processes at work during the radiation of Tamias and suggest
      that sampling reproductive-protein genes may be a viable strategy for phylogeny
      estimation of rapid radiations in which reproductive isolation is incomplete.
      However, a genome-scale survey that can statistically compare heterogeneity of
      genealogical process at many more loci will be necessary to test this conclusion.

PMID- 21878473
TI  - Depression and outcomes of dialysis patients.

PMID- 21878474
TI  - Inequalities in rates of renal replacement therapy in England: does it matter who
      you are or where you live?
AB  - Introduction. This study explores the geographical variation in renal replacement
      therapy (RRT) incidence and prevalence after adjusting for general population
      socio-demographics, renal unit treatment patterns and travel times. METHODS: The
      UK Renal Registry provided data on all patients in England commencing RRT in 2007
      and receiving RRT on 31 December 2007. Multilevel Poisson regression models were
      constructed separately for incidence and prevalence. Geographical Information
      Systems software enabled estimation of road travel times and renal unit catchment
      areas. Small area estimates of RRT prevalence were produced for all 354 local
      authority districts. RESULTS: Adjusted RRT incidence rates were 1.4 (95%
      confidence interval 1.2-1.6) times higher in the most deprived areas and 1.7 (1.5
      2.0) and 1.5 (1.3-1.7) times higher in areas with most Black and South Asian
      inhabitants (10+%), respectively. The proportion of a centre's patients on
      haemodialysis or transplanted were positively associated with RRT incidence (not
      prevalence); numbers of satellite units were negatively associated with RRT
      incidence (not prevalence). While only 3% of patients lived >30 min from a
      dialysis unit, there was an effect of travel time on RRT rates; individuals
      living 45+ min from a dialysis unit were 20% less likely to commence or receive
      RRT than those living within 15 min (Ptrend=0.36 and Ptrend<0.001, respectively).
      A 4-fold variation in adjusted local authority district RRT prevalence rates
      could not be explained. CONCLUSION: Expansion of renal unit facilities in England
      has reduced travel times in most areas though the possibility of inequitable
      geographic access to RRT persists.

PMID- 21878475
TI  - On the impossibility to translate experience and the role of patient narratives
      in dialysis choices.

PMID- 21878477
TI  - Solitary fibrous tumor of the central nervous system: report of an additional 5
      cases with comprehensive literature review.
AB  - Solitary fibrous tumor (SFT) of the central nervous system was first described in
      1996. A number of cases have been reported since. The authors present 5 new
      cases: 4 intracranial and 1 intraspinal. All patients were adults (age range, 47
      to 75 years); 4 were male and 1 female; 4 cases were primary tumors; and 1 was a
      second tumor recurrence. All patients were surgically treated with gross total
      removal. All cases were histologically examined with immunohistochemical
      confirmation; 2 tumors exhibited diffuse classic histology, 1 tumor was a
      cellular variant, 1 tumor was myxoid, and 1 was predominantly classic with focal
      myxoid features and focally pleomorphic. The postoperative course was uneventful
      in all. The patient with the cellular variant experienced 2 local recurrences and
      eventually died of disease 10 years after the initial diagnosis. The patient with
      the myxoid variant--the tumor studied--which was the second recurrence of a
      previously misdiagnosed fibrous meningioma surgically treated 15 years earlier,
      had a recurrence after 2 years for the third time and eventually died of disease.
      Three patients are alive and well 11.6, 6, and 4 years after surgery. SFT is a
      rare tumor that needs to be differentiated from some mimickers, mainly fibrous
      meningioma, hemangiopericytoma, and with regard to the myxoid variant, also adult
      onset myxochordoid meningioma and myxoid peripheral nerve sheath tumor.
      Immunohistochemistry is crucial for the correct diagnosis of SFT. The authors
      also performed a review of the literature and found a little more than 200 cases
      on record.

PMID- 21878476
TI  - Posttranscriptional regulation of expression of plasminogen activator inhibitor
      type-1 by cAMP in HepG2 liver cells.
AB  - Altered expression of plasminogen activator inhibitor type-1 (PAI-1), a
      physiologic fibrinolysis inhibitor, is implicated in atherosclerosis. Cyclic
      adenosine monophosphate (cAMP) alters PAI-1 expression in several cells.
      Nevertheless, posttranscriptional regulation of PAI-1 has not been elucidated. To
      determine whether cAMP affects PAI-1 expression at posttranscriptional level, we
      determined promoter activity, mRNA levels, 3'-untranslated region (UTR) activity
      and protein levels of PAI-1 using HepG2 cells. cAMP decreased PAI-1 promoter
      activity at 24 h and mRNA expression at 4 h while it increased mRNA expression
      and accumulation of PAI-1 protein into media at 24 h. Human PAI-1 mRNA exists in
      two subspecies (3.2 and 2.2 kb), and cAMP increased baseline luciferase activity
      of 3'-UTR of the 3.2 kb PAI-1 mRNA [3'-UTR (+1358-3176)] and 1 kb fragment of 3'
      terminus of 3'-UTR of 3.2 kb mRNA [3'-UTR (+2177-3176)]. cAMP increased PAI-1
      protein expression despite decrease in promoter activity, presumably by
      regulating PAI-1 expression at the posttranscriptional level and thereby
      affecting mRNA stability. The 53-nt fragment in 3'-UTR (+2591 to +2643 nt) was
      involved in posttranscriptional regulation by cAMP. Thus, cAMP can stabilize 3.2
      kb PAI-1 mRNA mediated by specific effects on 3'-UTR, and these effects are
      associated with increased expression of PAI-1 protein.

PMID- 21878478
TI  - Correcting the persistently abducted little finger using a distally based
      extensor digiti minimi tendon.

PMID- 21878479
TI  - A modified technique to reconstruct the scapholunate ligament using a slip of
      flexor carpi radialis tendon.

PMID- 21878480
TI  - Friction neuropathy of ulnar digital nerve in a writer's thumb which was
      successfully treated with corticosteroid injection.

PMID- 21878481
TI  - Is liver SUV stable over time in 18F-FDG PET imaging?
AB  - This work investigated whether (18)F-FDG PET standardized uptake value (SUV) is
      stable over time in the normal human liver. METHODS: The SUV-versus-time curve,
      SUV(t), of (18)F-FDG in the normal human liver was derived from a kinetic model
      analysis. This derivation involved mean values of (18)F-FDG liver metabolism that
      were obtained from a patient series (n = 11), and a noninvasive population-based
      input function was used in each individual. RESULTS: Mean values (+/-95%
      reliability limits) of the (18)F-FDG uptake and release rate constant and of the
      fraction of free tracer in blood and interstitial volume were as follows: K =
      0.0119 mL.min(-1).mL(-1) (+/-0.0012), k(R) = 0.0065.min(-1) (+/-0.0009), and F =
      0.21 mL.mL(-1) (+/-0.11), respectively. SUV(t) (corrected for (18)F physical
      decay) was derived from these mean values, showing that it smoothly peaks at 75
      80 min on average after injection and that it is within 5% of the peak value
      between 50 and 110 min after injection. CONCLUSION: In the normal human liver,
      decay-corrected SUV(t) remains nearly constant (with a reasonable +/-2.5%
      relative measurement uncertainty) if the time delay between tracer injection and
      PET acquisition is in the range of 50-110 min. In current clinical practice, the
      findings suggest that SUV of the normal liver can be used for comparison with SUV
      of suspected malignant lesions, if comparison is made within this time range.

PMID- 21878482
TI  - Association of spinal muscle composition and prevalence of hyperkyphosis in
      healthy community-dwelling older men and women.
AB  - BACKGROUND: Older adults with hyperkyphosis are at increased risk of falls,
      fractures, and functional decline. Modifiable risk factors for hyperkyphosis have
      not been well studied. Our objective was to determine whether spinal muscle area
      and density are associated with hyperkyphosis, independent of age, race, sex,
      bone mineral density, and trunk fat. METHODS: Using data from the Pittsburgh site
      of the Health, Aging, and Body Composition study, we performed a baseline cross
      sectional analysis. Participants were black and white men and women 70-79 years
      old (N = 1172), independent in activities of daily living and able to walk
      &frac14; mile and up 10 steps without resting. We measured Cobb's angle of
      kyphosis from supine lateral scout computed tomography scans, and categorized
      hyperkyphosis as Cobb's angle >40 degrees . Axial images from lateral scout
      computed tomography scans assessed spinal extensor muscle cross-sectional area
      and density (proxy for fat infiltration). RESULTS: In our sample, 21% had
      hyperkyphosis. Prevalence in black men was 11%; in white men, 17%; in black
      women, 26%; and in white women, 30%. In multivariate analysis, each standard
      deviation increase in muscle density was associated with a 29% reduction in the
      odds of hyperkyphosis, independent of covariates. Muscle area was not
      significantly associated with hyperkyphosis. CONCLUSIONS: Lower spinal muscle
      density is associated with hyperkyphosis in healthy community-dwelling older
      adults. This potentially modifiable risk factor could be targeted in exercise
      interventions. Randomized trials are needed to determine whether an exercise
      program targeting spinal muscle density reduces hyperkyphosis and in turn
      improves health outcomes.

PMID- 21878483
TI  - Laterality patterns of brain functional connectivity: gender effects.
AB  - Lateralization of brain connectivity may be essential for normal brain function
      and may be sexually dimorphic. Here, we study the laterality patterns of short
      range (implicated in functional specialization) and long-range (implicated in
      functional integration) connectivity and the gender effects on these laterality
      patterns. Parallel computing was used to quantify short- and long-range
      functional connectivity densities in 913 healthy subjects. Short-range
      connectivity was rightward lateralized and most asymmetrical in areas around the
      lateral sulcus, whereas long-range connectivity was rightward lateralized in
      lateral sulcus and leftward lateralizated in inferior prefrontal cortex and
      angular gyrus. The posterior inferior occipital cortex was leftward lateralized
      (short- and long-range connectivity). Males had greater rightward lateralization
      of brain connectivity in superior temporal (short- and long-range), inferior
      frontal, and inferior occipital cortices (short-range), whereas females had
      greater leftward lateralization of long-range connectivity in the inferior
      frontal cortex. The greater lateralization of the male's brain (rightward and
      predominantly short-range) may underlie their greater vulnerability to disorders
      with disrupted brain asymmetries (schizophrenia, autism).

PMID- 21878484
TI  - Similarity-based extraction of individual networks from gray matter MRI scans.
AB  - The characterization of gray matter morphology of individual brains is an
      important issue in neuroscience. Graph theory has been used to describe cortical
      morphology, with networks based on covariation of gray matter volume or thickness
      between cortical areas across people. Here, we extend this research by proposing
      a new method that describes the gray matter morphology of an individual cortex as
      a network. In these large-scale morphological networks, nodes represent small
      cortical regions, and edges connect regions that have a statistically similar
      structure. The method was applied to a healthy sample (n = 14, scanned at 2
      different time points). For all networks, we described the spatial degree
      distribution, average minimum path length, average clustering coefficient, small
      world property, and betweenness centrality (BC). Finally, we studied the
      reproducibility of all these properties. The networks showed more clustering than
      random networks and a similar minimum path length, indicating that they were
      "small world." The spatial degree and BC distributions corresponded closely to
      those from group-derived networks. All network property values were reproducible
      over the 2 time points examined. Our results demonstrate that intracortical
      similarities can be used to provide a robust statistical description of
      individual gray matter morphology.

PMID- 21878486
TI  - Evidence that microglia mediate the neurobiological effects of chronic
      psychological stress on the medial prefrontal cortex.
AB  - Psychological stress contributes to the development of clinical depression. This
      has prompted many preclinical studies to investigate the neurobiology of this
      relationship, however, the effects of stress on glia remain unclear. In this
      study, we wished to determine, first, how exposure to chronic psychological
      stress affects microglial activity within the prefrontal cortex (PFC) and,
      second, whether the observed changes were meaningfully related to corresponding
      changes in local neuronal activity and PFC-regulated behavior. Therefore, we
      examined markers of microglial activation, antigen presentation, apoptosis, and
      persistent neuronal activation within the PFC after exposure to repeated
      restraint stress. We also examined the effect of stress on spatial working
      memory, a PFC-dependent function. Finally, we tested the ability of a microglial
      activation inhibitor (minocycline) to alter the impact of chronic stress on all
      of these endpoints. Stressor exposure produced positively correlated increases in
      microglial and long-term neuronal activation in the PFC but not antigen
      presentation or apoptosis. As expected, it also impaired spatial working memory.
      Importantly, minocycline reduced the impact of stress on neuronal activation and
      working memory, as well as microglial activation. These results suggest a role
      for microglia in mediating the effects of stress on PFC neuronal function and PFC
      regulated behavior.

PMID- 21878485
TI  - Transgenic overexpression of the type I isoform of neuregulin 1 affects working
      memory and hippocampal oscillations but not long-term potentiation.
AB  - Neuregulin 1 (NRG1) is a growth factor involved in neurodevelopment and
      plasticity. It is a schizophrenia candidate gene, and hippocampal expression of
      the NRG1 type I isoform is increased in the disorder. We have studied transgenic
      mice overexpressing NRG1 type I (NRG1(tg-type I)) and their wild-type littermates
      and measured hippocampal electrophysiological and behavioral phenotypes. Young
      NRG1(tg-type I) mice showed normal memory performance, but in older NRG1(tg-type
      I) mice, hippocampus-dependent spatial working memory was selectively impaired.
      Hippocampal slice preparations from NRG1(tg-type I) mice exhibited a reduced
      frequency of carbachol-induced gamma oscillations and an increased tendency to
      epileptiform activity. Long-term potentiation in NRG1(tg-type I) mice was normal.
      The results provide evidence that NRG1 type I impacts on hippocampal function and
      circuitry. The effects are likely mediated via inhibitory interneurons and may be
      relevant to the involvement of NRG1 in schizophrenia. However, the findings, in
      concert with those from other genetic and pharmacological manipulations of NRG1,
      emphasize the complex and pleiotropic nature of the gene, even with regard to a
      single isoform.

PMID- 21878487
TI  - CoREST/LSD1 control the development of pyramidal cortical neurons.
AB  - The development of a neuron from a precursor cell comprises a complex set of
      steps ranging from regulation of the proliferative cycle through the acquisition
      of distinct morphology and functionality. How these processes are orchestrated is
      largely unknown. Using in utero manipulation of gene expression in the mouse
      embryonic cerebral cortex, we found that the transition between multipolar and
      bipolar stages of newborn cortical pyramidal neurons is markedly delayed by
      depletion of CoREST, a corepressor component of chromatin remodeling complexes.
      This profoundly affects the onset of their radial migration. The loss of CoREST
      function also perturbs the dynamics of neuronal precursor cell populations,
      transiently increasing the fraction of cells remaining in progenitor states, but
      not the acquisition of the neuronal glutamatergic fate of pyramidal cells. The
      function of CoREST in these processes appears to be independent of its best-known
      interactor, the RE-1 silencer of transcription/neural restrictive silencing
      factor, and requires the histone demethylase LSD1. This reveals the importance of
      epigenetic control in the execution of neural development programs, specifically
      in the cerebral cortex.

PMID- 21878489
TI  - Comparison of quantities: core and format-dependent regions as revealed by fMRI.
AB  - The perception and handling of numbers is central to education. Numerous imaging
      studies have focused on how quantities are encoded in the brain. Yet, only a few
      studies have touched upon number mining: the ability to extract the magnitude
      encoded in a visual stimulus. This article aims to characterize how analogue
      (i.e., disks and dots) and symbolic (i.e., positive and negative integers)
      formats influence number mining and the representation of quantities. Sixteen
      adult volunteers completed a comparison task while we recorded the blood oxygen
      level-dependent response using functional magnetic resonance imaging. The results
      revealed that a restricted set of specific subdivisions in the right
      intraparietal sulcus is activated in all conditions. With respect to magnitude
      assessment, the results show that 1) analogue stimuli are predominantly processed
      in the right hemisphere and that 2) symbolic stimuli encompass the analogue
      system and further recruit areas in the left hemisphere. Crucially, we found that
      polarity is encoded independently from magnitude. We refine the triple-code model
      by integrating our findings.

PMID- 21878488
TI  - Hemispheric specialization for movement control produces dissociable differences
      in online corrections after stroke.
AB  - In this study, we examine whether corrections made during an ongoing movement are
      differentially affected by left hemisphere damage (LHD) and right hemisphere
      damage (RHD). Our hypothesis of motor lateralization proposes that control
      mechanisms specialized to the right hemisphere rely largely on online processes,
      while the left hemisphere primarily utilizes predictive mechanisms to specify
      optimal coordination patterns. We therefore predict that RHD, but not LHD, should
      impair online correction when task goals are unexpectedly changed. Fourteen
      stroke subjects (7 LHD, 7 RHD) and 14 healthy controls reached to 1 of the 3
      targets that unexpectedly "jumped" during movement onset. RHD subjects showed a
      considerable delay in initiating the corrective response relative to controls and
      LHD subjects. However, both stroke groups made large final position errors on the
      target jump trials. Position deficits following LHD were associated with poor
      intersegmental coordination, while RHD subjects had difficulty terminating their
      movements appropriately. These findings confirm that RHD, but not LHD, produces a
      deficit in the timing of online corrections and also indicate that both stroke
      groups show position deficits that are related to the specialization of their
      damaged hemisphere. Further research is needed to identify specific neural
      circuits within each hemisphere critical for these processes.

PMID- 21878490
TI  - ERBIN is a new SARA-interacting protein: competition between SARA and SMAD2 and
      SMAD3 for binding to ERBIN.
AB  - SARA, an early endosomal protein, plays a key role in TGFbeta signalling, as it
      presents SMAD2 and SMAD3 for phosphorylation by the activated TGFbeta receptors.
      Here, we show that ERBIN is a new SARA-interacting protein that can be recruited
      by SARA to early endosomes. ERBIN was recently shown to bind and segregate
      phosphorylated SMAD2 and SMAD3 (SMAD2/3) in the cytoplasm, thereby inhibiting
      SMAD2/3-dependent transcription. SARA binds to ERBIN using a new domain, which we
      have called the ERBID (ERBIN-binding domain), whereas ERBIN binds to SARA using a
      domain (amino acids 1208-1265) that also interacts with SMAD2 and SMAD3, which we
      have called the SSID (SARA- and SMAD-interacting domain). We additionally show
      that SARA competes with SMAD2/3 for binding to ERBIN. In agreement,
      overexpression of SARA or the ERBID peptide reverses the inhibitory effect of
      ERBIN on SMAD2/3-dependent transcription. Taken together, these data suggest that
      the response of cells to TGFbeta and activin A can be influenced by the relative
      concentrations of SARA, ERBIN and SMAD2/3.

PMID- 21878491
TI  - Identification of SH2B1beta as a focal adhesion protein that regulates focal
      adhesion size and number.
AB  - The adaptor protein SH2B1beta participates in regulation of the actin
      cytoskeleton during processes such as cell migration and differentiation. Here,
      we identify SH2B1beta as a new focal adhesion protein. We provide evidence that
      SH2B1beta is phosphorylated in response to phorbol 12-myristate 13-acetate (PMA)
      induced protein kinase C (PKC) activation and show that PMA induces a rapid
      redistribution of SH2B1beta out of focal adhesions. We also show that growth
      hormone (GH) increases cycling of SH2B1beta into and out of focal adhesions.
      Ser161 and Ser165 in SH2B1beta fall within consensus PKC substrate motifs.
      Mutating these two serine residues into alanine residues abrogates PMA-induced
      redistribution of SH2B1beta out of focal adhesions, decreases SH2B1beta cycling
      into and out of focal adhesions in control and GH-stimulated cells, and increases
      the size of focal adhesions. By contrast, mutating Ser165 into a glutamate
      residue decreases the amount of SH2B1beta in focal adhesions and increases the
      number of focal adhesions per cell. These results suggest that activation of PKC
      regulates SH2B1beta focal adhesion localization through phosphorylation of Ser161
      and/or Ser165. The finding that phosphorylation of SH2B1beta increases the number
      of focal adhesions suggests a mechanism for the stimulatory effect on cell
      motility of SH2B1beta.

PMID- 21878494
TI  - Revolution II--you better change your mind instead. By Caveman.

PMID- 21878492
TI  - Adipophilin regulates maturation of cytoplasmic lipid droplets and alveolae in
      differentiating mammary glands.
AB  - Milk lipids originate by secretion of triglyceride-rich cytoplasmic lipid
      droplets (CLDs) from mammary epithelial cells. Adipophilin (ADPH)/Plin2, a member
      of the perilipin family of CLD binding proteins, is hypothesized to regulate CLD
      production in these cells during differentiation of the mammary gland into a
      secretory organ. We tested this hypothesis by comparing CLD accumulation in
      differentiating mammary glands of wild-type and ADPH-deficient mice. ADPH
      deficiency did not prevent CLD formation; however, it disrupted the increase in
      CLD size that normally occurs in differentiating mammary epithelial cells.
      Failure to form large CLDs in ADPH-deficient mice correlated with localization of
      adipose triglyceride lipase (ATGL) to the CLD surface, suggesting that ADPH
      promotes CLD growth by inhibiting lipolytic activity. Significantly, mammary
      alveoli also failed to mature in ADPH-deficient mice, and pups born to these mice
      failed to survive. The possibility that CLD accumulation and alveolar maturation
      defects in ADPH-deficient mice are functionally related was tested by in vivo
      rescue experiments. Transduction of mammary glands of pregnant ADPH-deficient
      mice with adenovirus encoding ADPH as an N-terminal GFP fusion protein prevented
      ATGL from localizing to CLDs and rescued CLD size and alveolar maturation
      defects. Collectively, these data provide direct in vivo evidence that ADPH
      inhibition of ATGL-dependent lipolysis is required for normal CLD accumulation
      and alveolar maturation during mammary gland differentiation. We speculate that
      impairing CLD accumulation interferes with alveolar maturation and lactation by
      disrupting triglyceride homeostasis in mammary epithelial cells.

PMID- 21878493
TI  - Importance of PKCdelta signaling in fractionated-radiation-induced expansion of
      glioma-initiating cells and resistance to cancer treatment.
AB  - Brain tumors frequently recur or progress as focal masses after treatment with
      ionizing radiation. However, the mechanisms underlying the repopulation of tumor
      cells after radiation have remained unclear. In this study, we show that cellular
      signaling from Abelson murine leukemia viral oncogene homolog (Abl) to protein
      kinase Cdelta (PKCdelta) is crucial for fractionated-radiation-induced expansion
      of glioma-initiating cell populations and acquisition of resistance to anticancer
      treatments. Treatment of human glioma cells with fractionated radiation increased
      Abl and PKCdelta activity, expanded the CD133-positive (CD133(+)) cell population
      that possesses tumor-initiating potential and induced expression of glioma stem
      cell markers and self-renewal-related proteins. Moreover, cells treated with
      fractionated radiation were resistant to anticancer treatments. Small interfering
      RNA (siRNA)-mediated knockdown of PKCdelta expression blocked fractionated
      radiation-induced CD133(+) cell expansion and suppressed expression of glioma
      stem cell markers and self-renewal-related proteins. It also suppressed
      resistance of glioma cells to anticancer treatments. Similarly, knockdown of Abl
      led to a decrease in CD133(+) cell populations and restored chemotherapeutic
      sensitivity. It also attenuated fractionated-radiation-induced PKCdelta
      activation, suggesting that Abl acts upstream of PKCdelta. Collectively, these
      data indicate that fractionated radiation induces an increase in the glioma
      initiating cell population, decreases cellular sensitivity to cancer treatment
      and implicates activation of Abl-PKCdelta signaling in both events. These
      findings provide insights that might prove pivotal in the context of ionising
      radiation-based therapeutic interventions for brain tumors.

PMID- 21878495
TI  - Imaging molecular dynamics in vivo--from cell biology to animal models.
AB  - Advances in fluorescence microscopy have enabled the study of membrane diffusion,
      cell adhesion and signal transduction at the molecular level in living cells
      grown in culture. By contrast, imaging in living organisms has primarily been
      restricted to the localization and dynamics of cells in tissues. Now, imaging of
      molecular dynamics is on the cusp of progressing from cell culture to living
      tissue. This transition has been driven by the understanding that the
      microenvironment critically determines many developmental and pathological
      processes. Here, we review recent progress in fluorescent protein imaging in vivo
      by drawing primarily on cancer-related studies in mice. We emphasize the need for
      techniques that can be easily combined with genetic models and complement
      fluorescent protein imaging by providing contextual information about the
      cellular environment. In this Commentary we will consider differences between in
      vitro and in vivo experimental design and argue for an approach to in vivo
      imaging that is built upon the use of intermediate systems, such as 3-D and
      explant culture models, which offer flexibility and control that is not always
      available in vivo. Collectively, these methods present a paradigm shift towards
      the molecular-level investigation of disease and therapy in animal models of
      disease.

PMID- 21878496
TI  - The Aurora kinase Ipl1 is necessary for spindle pole body cohesion during budding
      yeast meiosis.
AB  - In budding yeast, the microtubule-organizing center is called the spindle pole
      body (SPB) and shares structural components with the centriole, the central core
      of the animal centrosome. During meiotic interphase I, the SPB is duplicated when
      DNA replication takes place. Duplicated SPBs are linked and then separate to form
      a bipolar spindle required for homolog separation in meiosis I. During interphase
      II, SPBs are duplicated again, in the absence of DNA replication, to form four
      SPBs that establish two spindles for sister-chromatid separation in meiosis II.
      Here, we report that the Aurora kinase Ipl1, which is necessary for sister
      chromatid cohesion, is also required for maintenance of a tight association
      between duplicated SPBs during meiosis, which we term SPB cohesion. Premature
      loss of cohesion leads to SPB overduplication and the formation of multipolar
      spindles. By contrast, the Polo-like kinase Cdc5 is necessary for SPB duplication
      and interacts antagonistically with Ipl1 at the meiotic SPB to ensure proper SPB
      separation. Our data suggest that Ipl1 coordinates SPB dynamics with the two
      chromosome segregation cycles during yeast meiosis.

PMID- 21878497
TI  - RhoG is required for both FcgammaR- and CR3-mediated phagocytosis.
AB  - Phagocytosis is a highly ordered process orchestrated by signalling through Rho
      GTPases to locally organise the actin cytoskeleton and drive particle uptake.
      Specific Rho family members that regulate phagocytosis are not known, as the
      majority of studies have relied on the use of dominant-negative mutants and/or
      toxins, which can inactivate multiple Rho GTPases. To identify the relevant
      GTPases for phagocytosis through the Fcgamma receptor (FcgammaR) and complement
      receptor 3 (CR3), we depleted 20 Rho proteins individually in an RNA interference
      (RNAi) screen. We find that distinct GTPase subsets are required for actin
      polymerisation and uptake by macrophages: FcgammaR-dependent engulfment requires
      Cdc42 and Rac2 (but not Rac1), whereas CR3 requires RhoA. Surprisingly, RhoG is
      required for particle uptake through both FcgammaR and CR3. RhoG has been
      previously linked to Rac and Cdc42 signalling in different model systems, but not
      to RhoA. Interestingly, we find that RhoG is also recruited and activated at
      phagocytic cups downstream of FcgammaR and CR3, irrespective of their distinct
      actin structures and mechanisms of internalisation. Thus, the functional links
      between RhoG and RhoA downstream of CR3-dependent phagocytosis are new and
      unexpected. Our data suggest a broad role for RhoG in consolidating signals from
      multiple receptors during phagocytosis.

PMID- 21878499
TI  - Annexin B9 binds to beta(H)-spectrin and is required for multivesicular body
      function in Drosophila.
AB  - The role of the cytoskeleton in protein trafficking is still being defined. Here,
      we describe a relationship between the small Ca(2+)-dependent membrane-binding
      protein Annexin B9 (AnxB9), apical beta(Heavy)-spectrin (beta(H)) and the
      multivesicular body (MVB) in Drosophila. AnxB9 binds to a subset of beta(H)
      spliceoforms, and loss of AnxB9 results in an increase in basolateral beta(H) and
      its appearance on cytoplasmic vesicles that overlap with the MVB markers Hrs,
      Vps16 and EPS15. Similar colocalizations are seen when beta(H)-positive endosomes
      are generated either by upregulation of beta(H) in pak mutants or through the
      expression of the dominant-negative version of beta(H). In common with other
      mutations disrupting the MVB, we also show that there is an accumulation of
      ubiquitylated proteins and elevated EGFR signaling in the absence of AnxB9 or
      beta(H). Loss of AnxB9 or beta(H) function also causes the redistribution of the
      DE-Cadherin (encoded by shotgun) to endosomal vesicles, suggesting a rationale
      for the previously documented destabilization of the zonula adherens in karst
      (which encodes beta(H)) mutants. Reduction of AnxB9 results in degradation of the
      apical-lateral boundary and the appearance of the basolateral proteins Coracle
      and Dlg on internal vesicles adjacent to beta(H). These results indicate that
      AnxB9 and beta(H) are intimately involved in endosomal trafficking to the MVB and
      play a role in maintaining high-fidelity segregation of the apical and lateral
      domains.

PMID- 21878498
TI  - Protein phosphatase 5 is a negative regulator of separase function during
      cortical granule exocytosis in C. elegans.
AB  - Mutations in the Caenorhabditis elegans separase gene, sep-1, are embryonic
      lethal. Newly fertilized mutant embryos have defects in polar body extrusion,
      fail to undergo cortical granule exocytosis, and subsequently fail to complete
      cytokinesis. Chromosome nondisjunction during the meiotic divisions is readily
      apparent after depletion of sep-1 by RNAi treatment, but much less so in
      hypomorphic mutant embryos. To identify factors that influence the activity of
      separase in cortical granule exocytosis and cytokinesis, we carried out a genetic
      suppressor screen. A mutation in the protein phosphatase 5 (pph-5) gene was
      identified as an extragenic suppressor of sep-1. This mutation suppressed the
      phenotypes of hypomorphic separase mutants but not RNAi depleted animals.
      Depletion of pph-5 caused no phenotypes on its own, but was effective in
      restoring localization of mutant separase to vesicles and suppressing cortical
      granule exocytosis and cytokinesis phenotypes. The identification of PPH-5 as a
      suppressor of separase suggests that a new phospho-regulatory pathway plays an
      important role in regulating anaphase functions of separase.

PMID- 21878500
TI  - Lung-specific loss of the laminin alpha3 subunit confers resistance to mechanical
      injury.
AB  - Laminins are heterotrimeric glycoproteins of the extracellular matrix that are
      secreted by epithelial cells and which are crucial for the normal structure and
      function of the basement membrane. We have generated a mouse harboring a
      conditional knockout of alpha3 laminin (Lama3(fl/fl)), one of the main laminin
      subunits in the lung basement membrane. At 60 days after intratracheal treatment
      of adult Lama3(fl/fl) mice with an adenovirus encoding Cre recombinase (Ad-Cre),
      the protein abundance of alpha3 laminin in whole lung homogenates was more than
      50% lower than that in control-treated mice, suggesting a relatively long half
      life for the protein in the lung. Upon exposure to an injurious ventilation
      strategy (tidal volume of 35 ml per kg of body weight for 2 hours), the mice with
      a knockdown of the alpha3 laminin subunit had less severe injury, as shown by
      lung mechanics, histology, alveolar capillary permeability and survival when
      compared with Ad-Null-treated mice. Knockdown of the alpha3 laminin subunit
      resulted in evidence of lung inflammation. However, this did not account for
      their resistance to mechanical ventilation. Rather, the loss of alpha3 laminin
      was associated with a significant increase in the collagen content of the lungs.
      We conclude that the loss of alpha3 laminin in the alveolar epithelium results in
      an increase in lung collagen, which confers resistance to mechanical injury.

PMID- 21878501
TI  - Activation of Src induces mitochondrial localisation of de2-7EGFR (EGFRvIII) in
      glioma cells: implications for glucose metabolism.
AB  - A common mutation of the epidermal growth factor receptor in glioma is the de2
      7EGFR (or EGFRvIII). Glioma cells expressing de2-7EGFR contain an intracellular
      pool of receptor with high levels of mannose glycosylation, which is consistent
      with delayed processing. We now show that this delay occurs in the Golgi complex.
      Low levels of de2-7EGFR were also seen within the mitochondria. Src activation
      dramatically increased the amount of mitochondrial de2-7EGFR, whereas its
      pharmacological inhibition caused a significant reduction. Because de2-7EGFR is
      phosphorylated by Src at Y845, we generated glioma cells expressing a Y845F
      modified de2-7EGFR. The de2-7EGFR(845F) mutant failed to show mitochondrial
      localisation, even when co-expressed with constitutive active Src. Low levels of
      glucose enhanced mitochondrial localisation of de2-7EGFR, and glioma cells
      expressing the receptor showed increased survival and proliferation under these
      conditions. Consistent with this, de2-7EGFR reduced glucose dependency by
      stimulating mitochondrial oxidative metabolism. Thus, the mitochondrial
      localisation of de2-7EGFR contributes to its tumorigenicity and might help to
      explain its resistance to some EGFR-targeted therapeutics.

PMID- 21878502
TI  - Chromosomal breaks during mitotic catastrophe trigger gammaH2AX-ATM-p53-mediated
      apoptosis.
AB  - Although the cause and outcome of mitotic catastrophe (MC) has been thoroughly
      investigated, precisely how the ensuing lethality is regulated during or
      following this process and what signals are involved remain unknown. Moreover,
      the mechanism of the decision of cell death modalities following MC is still not
      well characterised. We demonstrate here a crucial role of the gammaH2AX-ATM-p53
      pathway in the regulation of the apoptotic outcome of MC resulting from cells
      entering mitosis with damaged DNA. In addition to p53 deficiency, the depletion
      of ATM (ataxia telangiectasia mutated), but not ATR (ataxia telangiectasia and
      Rad3-related protein), protected against apoptosis and shifted cell death towards
      necrosis. Activation of this pathway is triggered by the augmented chromosomal
      damage acquired during anaphase in doxorubicin-treated cells lacking 14-3-3sigma
      (also known as epithelial cell marker protein-1 or stratifin). Moreover, cells
      that enter mitosis with damaged DNA encounter segregation problems because of
      their abnormal chromosomes, leading to defects in mitotic exit, and they
      therefore accumulate in G1 phase. These multi- or micronucleated cells are
      prevented from cycling again in a p53- and p21-dependent manner, and subsequently
      die. Because increased chromosomal damage resulting in extensive H2AX
      phosphorylation appears to be a direct cause of catastrophic mitosis, our results
      describe a mechanism that involves generation of additional DNA damage during MC
      to eliminate chromosomally unstable cells.

PMID- 21878503
TI  - Scaffolding function of the Chlamydomonas procentriole protein CRC70, a member of
      the conserved Cep70 family.
AB  - Centriole duplication occurs once per cell cycle through the assembly of daughter
      centrioles on the side wall of pre-existing centrioles. Little is known about the
      molecules involved in the assembly of new centrioles. Here, we identify CRC70 as
      a Chlamydomonas protein with an important role in the accumulation of centriole
      proteins at the site of assembly. CRC70 contains a highly conserved ~50-amino
      acid sequence shared by mammalian Cep70 and preferentially localizes to immature
      centrioles (the procentrioles). This localization is maintained in the mutant
      bld10, in which centriole formation is blocked before the assembly of centriolar
      microtubules. RNA interference (RNAi)-mediated knockdown of CRC70 produces
      flagella-less cells and inhibits the recruitment of other centriole components,
      such as SAS-6 and Bld10p to the centriole. Overexpression of CRC70 induces an
      accumulation of these proteins in discrete spots in the cytoplasm. Overexpression
      of EGFP-tagged CRC70 in mouse NIH3T3 cells causes the formation of structures
      apparently related to centrioles. These findings suggest that CRC70 is a member
      of a conserved protein family and functions as a scaffold for the assembly of the
      centriole precursor.

PMID- 21878504
TI  - Regulation of sororin by Cdk1-mediated phosphorylation.
AB  - Tumor cells are commonly aneuploid, a condition contributing to cancer
      progression and drug resistance. Understanding how chromatids are linked and
      separated at the appropriate time will help uncover the basis of aneuploidy and
      will shed light on the behavior of tumor cells. Cohesion of sister chromatids is
      maintained by the multi-protein complex cohesin, consisting of Smc1, Smc3, Scc1
      and Scc3. Sororin associates with the cohesin complex and regulates the
      segregation of sister chromatids. Sororin is phosphorylated in mitosis; however,
      the role of this modification is unclear. Here we show that mutation of potential
      cyclin-dependent kinase 1 (Cdk1) phosphorylation sites leaves sororin stranded on
      chromosomes and bound to cohesin throughout mitosis. Sororin can be precipitated
      from cell lysates with DNA-cellulose, and only the hypophosphorylated form of
      sororin shows this association. These results suggest that phosphorylation of
      sororin causes its release from chromatin in mitosis. Also, the
      hypophosphorylated form of sororin increases cohesion between sister chromatids,
      suggesting that phosphorylation of sororin by Cdk1 influences sister chromatid
      cohesion. Finally, phosphorylation-deficient sororin can alleviate the mitotic
      block that occurs upon knockdown of endogenous sororin. This mitotic block is
      abolished by ZM447439, an Aurora kinase inhibitor, suggesting that prematurely
      separated sister chromatids activate the spindle assembly checkpoint through an
      Aurora kinase-dependent pathway.

PMID- 21878505
TI  - Disease-associated missense mutations in bestrophin-1 affect cellular trafficking
      and anion conductance.
AB  - Bestrophin-1, an integral membrane protein encoded by the BEST1 gene, is
      localized predominantly to the basolateral membrane of the retinal pigment
      epithelium. Mutations in the BEST1 gene have been associated with Best
      vitelliforme macular dystrophy (BMD), a central retinopathy with autosomal
      dominant inheritance and variable penetrance. Over 120 disease-causing mutations
      are known, the majority of which result in amino acid substitutions within four
      mutational hot-spot regions in the highly conserved N-terminal half of the
      protein. Although initially thought to impair Cl- channel function, the molecular
      pathology of BEST1 mutations is still controversial. We have analyzed the
      subcellular localization of 13 disease-associated BEST1 mutant proteins in
      polarized MDCK II cells, an established model of apical to basolateral protein
      sorting. Immunostaining demonstrated that nine of the 13 mutant proteins failed
      to integrate into the cell membrane. The defective proteins were predominantly
      retained in the cytoplasm, whereas wild-type bestrophin-1 revealed cell membrane
      localization. Functional analysis of I- fluxes in HEK-293 cells showed that all
      mutants exhibited a significant reduction in anion conductance. Our data indicate
      that defective intracellular trafficking could be a common cause of BMD
      accompanied by impaired anion conductance, representing a loss of anion channel
      function that is probably due to mistargeting of mutant protein.

PMID- 21878506
TI  - miR-216b suppresses tumor growth and invasion by targeting KRAS in nasopharyngeal
      carcinoma.
AB  - MicroRNAs (miRNAs) are small noncoding RNAs that are involved in various
      diseases, including cancer. In the present study, we found that miR-216b was
      downregulated in nasopharyngeal carcinoma (NPC) cell lines and specimens.
      Decreased expression of miR-216b was directly related to advanced clinical stage
      and lymph node metastasis. miR-216b levels correlated inversely with levels of
      KRAS protein during nasopharyngeal tumorigenesis. Furthermore, we demonstrated
      that miR-216b can bind to the 3' untranslated region (UTR) of KRAS and inhibit
      expression of the KRAS protein. Both in vitro and in vivo assays revealed that
      miR-216b attenuated NPC cell proliferation, invasion and tumor growth in nude
      mice. miR-216b exerts its tumor suppressor function through inhibition of the
      KRAS-related AKT and ERK pathways. Our findings provide, for the first time,
      significant clues regarding the role of miR-216b as a tumor suppressor by
      targeting KRAS in NPC.

PMID- 21878507
TI  - p38 MAPKs regulate the expression of genes in the dopamine synthesis pathway
      through phosphorylation of NR4A nuclear receptors.
AB  - In Drosophila, the melanization reaction is an important defense mechanism
      against injury and invasion of microorganisms. Drosophila tyrosine hydroxylase
      (TH, also known as Pale) and dopa decarboxylase (Ddc), key enzymes in the
      dopamine synthesis pathway, underlie the melanin synthesis by providing the
      melanin precursors dopa and dopamine, respectively. It has been shown that
      expression of Drosophila TH and Ddc is induced in various physiological and
      pathological conditions, including bacterial challenge; however, the mechanism
      involved has not been fully elucidated. Here, we show that ectopic activation of
      p38 MAPK induces TH and Ddc expression, leading to upregulation of melanization
      in the Drosophila cuticle. This p38-dependent melanization was attenuated by
      knockdown of TH and Ddc, as well as by that of Drosophila HR38, a member of the
      NR4A family of nuclear receptors. In mammalian cells, p38 phosphorylated
      mammalian NR4As and Drosophila HR38 and potentiated these NR4As to transactivate
      a promoter containing NR4A-binding elements, with this transactivation being, at
      least in part, dependent on the phosphorylation. This suggests an evolutionarily
      conserved role for p38 MAPKs in the regulation of NR4As. Thus, p38-regulated gene
      induction through NR4As appears to function in the dopamine synthesis pathway and
      may be involved in immune and stress responses.

PMID- 21878508
TI  - Selective inhibition of rRNA transcription downregulates E2F-1: a new p53
      independent mechanism linking cell growth to cell proliferation.
AB  - The tumour suppressor p53 negatively controls cell cycle progression in response
      to perturbed ribosome biogenesis in mammalian cells, thus coordinating growth
      with proliferation. Unlike mammalian cells, p53 is not involved in the growth
      control of proliferation in yeasts and flies. We investigated whether a p53
      independent mechanism of response to inadequate ribosome biogenesis rate is also
      present in mammalian cells. We studied the effect of specific inhibition of rRNA
      synthesis on cell cycle progression in human cancer cell lines using the small
      interfering RNA procedure to silence the POLR1A gene, which encodes the catalytic
      subunit of RNA polymerase I. We found that interference of POLR1A inhibited the
      synthesis of rRNA and hindered cell cycle progression in cells with inactivated
      p53, as a consequence of downregulation of the transcription factor E2F-1.
      Downregulation of E2F-1 was due to release of the ribosomal protein L11, which
      inactivated the E2F-1-stabilising function of the E3 ubiquitin protein ligase
      MDM2. These results demonstrated the existence of a p53-independent mechanism
      that links cell growth to cell proliferation in mammalian cells, and suggested
      that selective targeting of the RNA polymerase I transcription machinery might be
      advisable to hinder proliferation of p53-deficient cancer cells.

PMID- 21878509
TI  - Immunobiology of naive and genetically modified HLA-class-I-knockdown human
      embryonic stem cells.
AB  - Human embryonic stem cells (hESCs) can serve as a universal cell source for
      emerging cell or tissue replacement strategies, but immune rejection of hESC
      derivatives remains an unsolved problem. Here, we sought to describe the
      mechanisms of rejection for naive hESCs and upon HLA class I (HLA I) knockdown
      (hESC(KD)). hESCs were HLA I-positive but negative for HLA II and co-stimulatory
      molecules. Transplantation of naive hESC into immunocompetent Balb/c mice induced
      substantial T helper cell 1 and 2 (Th1 and Th2) responses with rapid cell death,
      but hESCs survived in immunodeficient SCID-beige recipients. Histology revealed
      mainly macrophages and T cells, but only scattered natural killer (NK) cells. A
      surge of hESC-specific antibodies against hESC class I, but not class II
      antigens, was observed. Using HLA I RNA interference and intrabody technology,
      HLA I surface expression of hESC(KD) was 88%-99% reduced. T cell activation after
      hESC(KD) transplantation into Balb/c was significantly diminished, antibody
      production was substantially alleviated, the levels of graft-infiltrating immune
      cells were reduced and the survival of hESC(KD) was prolonged. Because of their
      very low expression of stimulatory NK ligands, NK-susceptibility of naive hESCs
      and hESC(KD) was negligible. Thus, HLA I recognition by T cells seems to be the
      primary mechanism of hESC recognition, and T cells, macrophages and hESC-specific
      antibodies participate in hESC killing.

PMID- 21878510
TI  - Acute stress differentially affects aromatase activity in specific brain nuclei
      of adult male and female quail.
AB  - The rapid and temporary suppression of reproductive behavior is often assumed to
      be an important feature of the adaptive acute stress response. However, how this
      suppression operates at the mechanistic level is poorly understood. The enzyme
      aromatase converts testosterone to estradiol in the brain to activate
      reproductive behavior in male Japanese quail (Coturnix japonica). The discovery
      of rapid and reversible modification of aromatase activity (AA) provides a
      potential mechanism for fast, stress-induced changes in behavior. We investigated
      the effects of acute stress on AA in both sexes by measuring enzyme activity in
      all aromatase-expressing brain nuclei before, during, and after 30 min of acute
      restraint stress. We show here that acute stress rapidly alters AA in the male
      and female brain and that these changes are specific to the brain nuclei and sex
      of the individual. Specifically, acute stress rapidly (5 min) increased AA in the
      male medial preoptic nucleus, a region controlling male reproductive behavior; in
      females, a similar increase was also observed, but it appeared delayed (15 min)
      and had smaller amplitude. In the ventromedial and tuberal hypothalamus, regions
      associated with female reproductive behavior, stress induced a quick and
      sustained decrease in AA in females, but in males, only a slight increase
      (ventromedial) or no change (tuberal) in AA was observed. Effects of acute stress
      on brain estrogen production, therefore, represent one potential way through
      which stress affects reproduction.

PMID- 21878512
TI  - Differential regulation of gonadotropin receptors (fshr and lhcgr) by estradiol
      in the zebrafish ovary involves nuclear estrogen receptors that are likely
      located on the plasma membrane.
AB  - FSH and LH are gonadotropins (GTH) that control all major events of gonadal
      function. FSH and LH signal through their cognate receptors, FSH receptor and
      LH/choriogonadotropin receptor, respectively, across vertebrates. Compared with
      the information in mammals, very little is known about these receptors in fish,
      especially the regulation of their expression. In female zebrafish, fshr and
      lhcgr exhibit significant temporal difference in expression, with fshr increasing
      first when the follicles are activated to enter the vitellogenic growth phase and
      lhcgr lagging behind. This raises an interesting question on the differential
      regulation of these two GTH receptors (GTHR) during folliculogenesis. Using a
      primary follicle cell culture, the present study demonstrated that 17beta
      estradiol (E2), but not testosterone, was a potent endocrine hormone that
      differentially regulated the expression of fshr and lhcgr. Although E2 stimulated
      both receptors, its effect on the steady-state level of lhcgr mRNA was much
      higher (>8-fold up-regulation) than that of fshr (~0.5-fold increase). E2 likely
      acted at the transcription level via its nuclear estrogen receptors (ERalpha and
      ERbeta), because ICI 182,780 could abolish its effects. However, our evidence
      suggested that these receptors might be localized on the plasma membrane, because
      beta-estradiol 6-(O-carboxy methyl)oxime:BSA could fully mimic the effects of E2.
      Demonstrating that E2 is likely one of the differentiating factors for the
      distinct expression of the two GTHR in the zebrafish ovary, this study sheds
      important light on the functions of the two GTH and their receptors in fish as
      well as the conservation and diverse aspects of GTHR regulation across
      vertebrates.

PMID- 21878513
TI  - Bombesin receptor subtype-3 (BRS-3) regulates glucose-stimulated insulin
      secretion in pancreatic islets across multiple species.
AB  - Bombesin receptor subtype-3 (BRS-3) regulates energy homeostasis, and BRS-3
      agonism is being explored as a possible therapy for obesity. Here we study the
      role of BRS-3 in the regulation of glucose-stimulated insulin secretion (GSIS)
      and glucose homeostasis. We quantified BRS-3 mRNA in pancreatic islets from
      multiple species and examined the acute effects of Bag-1, a selective BRS-3
      agonist, on GSIS in mouse, rat, and human islets, and on oral glucose tolerance
      in mice. BRS-3 is highly expressed in human, mouse, rhesus, and dog (but not rat)
      pancreatic islets and in rodent insulinoma cell lines (INS-1 832/3 and MIN6).
      Silencing BRS-3 with small interfering RNA or pharmacological blockade with a BRS
      3 antagonist, Bantag-1, reduced GSIS in 832/3 cells. In contrast, the BRS-3
      agonist (Bag-1) increased GSIS in 832/3 and MIN6 cells. The augmentation of GSIS
      by Bag-1 was completely blocked by U73122, a phospholipase C inhibitor. Bag-1
      also enhanced GSIS in islets isolated from wild-type, but not Brs3 knockout mice.
      In vivo, Bag-1 reduced glucose levels during oral glucose tolerance test in a BRS
      3-dependent manner. BRS-3 agonists also increased GSIS in human islets. These
      results identify a potential role for BRS-3 in islet physiology, with agonism
      directly promoting GSIS. Thus, in addition to its potential role in the treatment
      of obesity, BRS-3 may also regulate blood glucose levels and have a role in the
      treatment of diabetes mellitus.

PMID- 21878511
TI  - Minireview: The value of looking backward: the essential role of the hindbrain in
      counterregulatory responses to glucose deficit.
AB  - This review focuses on evidence indicating a key role for the hindbrain in
      mobilizing behavioral, autonomic and endocrine counterregulatory responses to
      acute and profound glucose deficit, and identifies hindbrain norepinephrine (NE)
      and epinephrine (E) neurons as essential mediators of some of these responses. It
      has become clear that hindbrain NE/E neurons are functionally diverse. However,
      considerable progress has been made in identifying the particular NE/E neurons
      important for particular glucoregulatory responses. Although it is not yet known
      whether NE/E neurons are directly activated by glucose deficit, compelling
      evidence indicates that if they are not, the primary glucoreceptor cells must be
      located in the immediate vicinity these neurons. Hindbrain studies identifying
      cellular markers associated with glucose-sensing functions in other brain regions
      are discussed, as are studies examining the relationship of these markers to
      counterregulatory responses of NE/E neurons. Further investigations to identify
      glucose-sensing cells (neurons, ependymocytes, or glia) controlling
      counterregulatory responses are crucial, as are studies to determine the specific
      functions of glucose-sensing cells throughout the brain. Likewise, examination of
      the roles (if any) of hindbrain counterregulatory systems in managing glucose
      homeostasis under basal, nonglucoprivic conditions will also be important for a
      full understanding of energy homeostasis. Nevertheless, the accumulated evidence
      demonstrates that hindbrain glucose sensors and NE/E neurons are essential
      players in triggering counterregulatory responses to emergencies of glucose
      deficit.

PMID- 21878514
TI  - CRH acts on CRH-R1 and -R2 to differentially modulate the expression of large
      conductance calcium-activated potassium channels in human pregnant myometrium.
AB  - CRH has been implicated to play a key role in the control of human pregnancy and
      parturition. Large-conductance potassium channels (BKCa) play a pivotal role in
      the modulation of uterine contractility during pregnancy. The objectives of the
      present study were to investigate the effect of CRH on BKCa expression in human
      pregnant myometrial cells. Myometrial tissues were collected at cesarean section
      from pregnant women not-in-labor (TNL) or in-labor (TL) at term, and myocytes
      were isolated and cultured. CRH was identified in human pregnant myometrium and
      mainly expressed in myometrial myocytes. Cultured myometrial cells were able to
      secrete CRH. In TNL myometrial cells, CRH treatment increased the expression of
      BKCa alpha- and beta-subunits. CRH receptor type 1 (CRH-R1) antagonist,
      antalarmin, decreased whereas CRH receptor type 2 (CRH-R2) antagonist,
      astressin2b, increased the expression of BKCa. CRH-R2 small interfering RNA
      (siRNA) caused an increase, but CRH-R1 siRNA resulted in a decrease, in BKCa
      expression. In contrast to TNL cells, CRH exhibited an opposite effect on BKCa
      expression in TL myometrial cells, i.e. decreased BKCa expression. Antalarmin
      enhanced but astressin2b reduced BKCa expression. CRH-R2 siRNA decreased whereas
      CRH-R1 siRNA increased BKCa expression. 1,3-Dihydro-1-[2-hydroxy-5
      (trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one significantly
      inhibited the frequency of spontaneous contractions of myometrial strips, and
      this effect was significantly decreased in TL strips compared with TNL ones. Our
      data suggest that CRH-R1 and CRH-R2 show differential regulation of BKCa
      expression. These effects mediated by CRH-R1 and CRH-R2 are changed after the
      onset of labor. This leads us to suggest that CRH may fine-tune myometrial
      contractility by modulating the expression of BKCa during pregnancy and labor.

PMID- 21878515
TI  - Developmental and cell-specific expression of thyroid hormone transporters in the
      mouse cochlea.
AB  - Thyroid hormone is essential for the development of the cochlea and auditory
      function. Cochlear response tissues, which express thyroid hormone receptor beta
      (encoded by Thrb), include the greater epithelial ridge and sensory epithelium
      residing inside the bony labyrinth. However, these response tissues lack direct
      blood flow, implying that mechanisms exist to shuttle hormone from the
      circulation to target tissues. Therefore, we investigated expression of candidate
      thyroid hormone transporters L-type amino acid transporter 1 (Lat1),
      monocarboxylate transporter (Mct)8, Mct10, and organic anion transporting
      polypeptide 1c1 (Oatp1c1) in mouse cochlear development by in situ hybridization
      and immunofluorescence analysis. L-type amino acid transporter 1 localized to
      cochlear blood vessels and transiently to sensory hair cells. Mct8 localized to
      the greater epithelial ridge, tympanic border cells underlying the sensory
      epithelium, spiral ligament fibrocytes, and spiral ganglion neurons, partly
      overlapping with the Thrb expression pattern. Mct10 was detected in a highly
      restricted pattern in the outer sulcus epithelium and weakly in tympanic border
      cells and hair cells. Organic anion transporting polypeptide 1c1 localized
      primarily to fibrocytes in vascularized tissues of the spiral limbus and spiral
      ligament and to tympanic border cells. Investigation of hypothyroid Tshr(-/-)
      mice showed that transporter expression was delayed consistent with retardation
      of cochlear tissue maturation but not with compensatory responses to
      hypothyroidism. The results demonstrate specific expression of thyroid hormone
      transporters in the cochlea and suggest that a network of thyroid hormone
      transport underlies cochlear development.

PMID- 21878516
TI  - Mutant p62P392L stimulation of osteoclast differentiation in Paget's disease of
      bone.
AB  - Paget's disease of the bone (PDB) is an autosomal dominant trait with genetic
      heterogeneity, characterized by abnormal osteoclastogenesis. Sequestosome 1 (p62)
      is a scaffold protein that plays an important role in receptor activator of
      nuclear factor kappaB (RANK) signaling essential for osteoclast (OCL)
      differentiation. p62P392L mutation in the ubiquitin-associated (UBA) domain is
      widely associated with PDB; however, the mechanisms by which p62P392L stimulate
      OCL differentiation in PDB are not completely understood. Deubiquitinating enzyme
      cylindromatosis (CYLD) has been shown to negatively regulate RANK ligand-RANK
      signaling essential for OCL differentiation. Here, we report that CYLD binds with
      the p62 wild-type (p62WT), non-UBA mutant (p62A381V) but not with the UBA mutant
      (p62P392L) in OCL progenitor cells. Also, p62P392L induces expression of c-Fos
      (2.8-fold) and nuclear factor of activated T cells c1 (6.0-fold) transcription
      factors critical for OCL differentiation. Furthermore, p62P392L expression
      results in accumulation of polyubiquitinated TNF receptor-associated factor
      (TRAF)6 and elevated levels of phospho-IkappaB during OCL differentiation.
      Retroviral transduction of p62P392L/CYLD short hairpin RNA significantly
      increased TRAP positive multinucleated OCL formation/bone resorption activity in
      mouse bone marrow cultures. Thus, the p62P392L mutation abolished CYLD
      interaction and enhanced OCL development/bone resorption activity in PDB.

PMID- 21878517
TI  - The phytoestrogen genistein is a tissue-specific androgen receptor modulator.
AB  - To enable studies of androgen signaling in different tissues in vivo, we
      generated an androgen receptor (AR) reporter mouse line by inserting a luciferase
      gene construct into the murine genome. The construct is driven by four copies of
      androgen-responsive elements from the mouse sex-limited protein gene (slp-HRE2)
      and a minimal thymidine kinase promoter. Luciferase activity was readily
      measurable in a number of murine tissues, including prostate, lung, testis,
      brain, and skeletal muscle, and testosterone administration elicited a
      significant increase in reporter gene activity in these tissues. Consumption of
      isoflavonoid genistein is linked to reduced risk of prostate cancer, but direct
      effects of genistein on the AR pathway are not well understood. To examine
      androgen-modulating activity of genistein in vivo, male mice received daily doses
      of genistein (10 mg/kg) for 5 d. In intact males, genistein was antiandrogenic in
      testis, prostate, and brain, and it attenuated reporter gene activity by 50-80%.
      In castrated males, genistein exhibited significant androgen agonistic activity
      in prostate and brain by increasing reporter gene activity over 2-fold in both
      tissues. No antiandrogenic action was seen in lung or skeletal muscle of intact
      males. Gene expression profiling of the murine prostate under the same
      experimental conditions revealed that genistein modulates androgen-dependent
      transcription program in prostate in a fashion similar to that observed in
      reporter mice by luciferase expression. In conclusion, genistein is a partial
      androgen agonist/antagonist in some but not in all mouse tissues and should be
      considered as a tissue-specific AR modulator.

PMID- 21878518
TI  - Transient expression of functional serotonin 5-HT3 receptors by glutamatergic
      granule cells in the early postnatal mouse cerebellum.
AB  - The serotonin 5-HT(3) receptor is the only ligand-gated ion channel activated by
      serotonin and is expressed by GABAergic interneurons in many brain regions,
      including the cortex, amygdala and hippocampus. Furthermore, 5-HT(3) receptors
      are expressed by glutamatergic Cajal-Retzius cells in the cerebral cortex. We
      used 5-HT(3A)/enhanced green fluorescent protein (EGFP) transgenic mice to show
      that 5-HT(3) receptors are also ubiquitously expressed by glutamatergic granule
      cells in the cerebellum during the first three postnatal weeks. Using whole-cell
      patch clamp recordings, we show that local application of either serotonin or the
      selective 5-HT(3) receptor agonist SR57227A to granule cells results in a small
      inward current, demonstrating a post- and/or extrasynaptic localisation of the 5
      HT(3) receptors. Functional 5-HT(3) receptors were also observed presynaptically
      at the parallel fibre-Purkinje cell synapse. Pharmacological block using the
      selective 5-HT(3) receptor antagonist tropisetron induced a reduction in the
      frequency of miniature synaptic events recorded from Purkinje cells. Paired-pulse
      stimulation of parallel fibres on whole-cell voltage clamped Purkinje cells from
      1-week-old mice did not yet show synaptic plasticity. In the presence of
      tropisetron, the parallel fibre-Purkinje cell synapse showed paired-pulse
      depression. Taken together, these results show that functional 5-HT(3) receptors
      are present during early postnatal development in the cerebellum, where they
      modulate synaptic plasticity.

PMID- 21878519
TI  - The primate reticulospinal tract, hand function and functional recovery.
AB  - The primate reticulospinal tract is usually considered to control proximal and
      axial muscles, and to be involved mainly in gross movements such as locomotion,
      reaching and posture. This contrasts with the corticospinal tract, which is
      thought to be involved in fine control, particularly of independent finger
      movements. Recent data provide evidence that the reticulospinal tract can exert
      some influence over hand movements. Although clearly secondary to the
      corticospinal tract in healthy function, this could assume considerable
      importance after corticospinal lesion (such as following stroke), when
      reticulospinal systems could provide a substrate for some recovery of function.
      We need to understand more about the abilities of the reticular formation to
      process sensory input and guide motor output, so that rehabilitation strategies
      can be optimised to work with the innate capabilities of reticular motor control.

PMID- 21878520
TI  - Implications of group III and IV muscle afferents for high-intensity endurance
      exercise performance in humans.
AB  - We investigated the influence of group III/IV muscle afferents on peripheral
      fatigue, central motor drive (CMD) and endurance capacity during high-intensity
      leg-cycling. In a double-blind, placebo-controlled design, seven males performed
      constant-load cycling exercise (318 +/- 9 W; 80% of peak power output (W(peak)))
      to exhaustion under placebo conditions and with lumbar intrathecal fentanyl
      impairing spinal MU-opioid receptor-sensitive group III/IV muscle afferents.
      Peripheral fatigue was assessed via changes in pre- vs. post-exercise quadriceps
      force in response to supramaximal magnetic femoral nerve stimulation
      (DeltaQ(tw,pot)). CMD was estimated via quadriceps electromyogram. To rule out a
      direct central effect of fentanyl, we documented unchanged resting
      cardioventilatory responses. Compared to placebo, significant hypoventilation
      during the fentanyl trial was indicated by the 9% lower V(E)/V(CO(2)), causing a
      5 mmHg increase in end-tidal P(CO(2)) and a 3% lower haemoglobin saturation.
      Arterial pressure and heart rate averaged 8 and 10% lower, respectively, during
      the fentanyl trial and these differences progressively diminished towards end
      exercise. Although initially similar, the percent change in CMD was 9 +/- 3%
      higher at end-exercise with fentanyl vs. placebo (P < 0.05). Time to exhaustion
      was shorter (6.8 +/- 0.3 min vs. 8.7 +/- 0.3 min) and end-exercise DeltaQ(tw,pot)
      was about one-third greater (-44 +/- 2% vs. -34 +/- 2%) following fentanyl vs.
      placebo. The rate of peripheral fatigue development was 67 +/- 10% greater during
      the fentanyl trial (P < 0.01). Our findings suggest that feedback from group
      III/IV muscle afferents limits CMD but also minimizes locomotor muscle fatigue
      development by stimulating adequate ventilatory and circulatory responses to
      exercise. In the face of blocked group III/IV muscle afferents, CMD is less
      inhibited but O(2) transport compromised and locomotor muscle fatigability is
      exacerbated with a combined net effect of a reduced endurance performance.

PMID- 21878521
TI  - SynDIG1 regulation of excitatory synapse maturation.
AB  - During development of the central nervous system (CNS), precise synaptic
      connections between pre- and postsynaptic neurons are formed that ultimately give
      rise to higher order cognitive skills such as learning and memory. Previously, my
      group identified a novel type II transmembrane protein, synapse differentiation
      induced gene 1 (SynDIG1), that regulates synaptic AMPA receptor content in
      dissociated rat hippocampal neurons. The magnitude of this effect matches that of
      the prototypical scaffold postsynaptic density protein of 95 kDa (PSD-95)
      identifying SynDIG1 as a previously unknown central regulator of excitatory
      synaptic strength. SynDIG1-mediated regulation of synaptic AMPA receptor
      targeting shares characteristics related to two distinct classes of transmembrane
      synaptic proteins: (1) ion channel auxiliary factors such as transmembrane AMPA
      receptor regulatory proteins (TARPs) important for AMPA receptor surface
      expression and channel gating properties; and (2) trans-synaptic organizing
      molecules such as leucine rich repeat transmembrane protein 2 (LRRTM2) that
      influence synapse maturation by recruitment of AMPA receptors to nascent
      synapses. An interesting aspect of SynDIG1 is that its distribution at excitatory
      synapses is regulated by activity, suggesting that SynDIG1 might also play a role
      in synaptic plasticity.

PMID- 21878522
TI  - Rearrangement of energetic and substrate utilization networks compensate for
      chronic myocardial creatine kinase deficiency.
AB  - Plasticity of the cellular bioenergetic system is fundamental to every organ
      function, stress adaptation and disease tolerance. Here, remodelling of
      phosphotransfer and substrate utilization networks in response to chronic
      creatine kinase (CK) deficiency, a hallmark of cardiovascular disease, has been
      revealed in transgenic mouse models lacking either cytosolic M-CK (M-CK(-/-)) or
      both M-CK and sarcomeric mitochondrial CK (M-CK/ScCKmit(-/-)) isoforms. The
      dynamic metabolomic signatures of these adaptations have also been defined.
      Tracking perturbations in metabolic dynamics with (18)O and (13)C isotopes and
      (31)P NMR and mass spectrometry demonstrate that hearts lacking M-CK have lower
      phosphocreatine (PCr) turnover but increased glucose-6-phosphate (G-6-P)
      turnover, glucose utilization and inorganic phosphate compartmentation with
      normal ATP gamma-phosphoryl dynamics. Hearts lacking both M-CK and sarcomeric
      mitochondrial CK have diminished PCr turnover, total phosphotransfer capacity and
      intracellular energetic communication but increased dynamics of beta-phosphoryls
      of ADP/ATP, G-6-P and gamma-/beta-phosphoryls of GTP, indicating redistribution
      of flux through adenylate kinase (AK), glycolytic and guanine nucleotide
      phosphotransfer circuits. Higher glycolytic and mitochondrial capacities and
      increased glucose tolerance contributed to metabolic resilience of M-CK/ScCKmit(
      /-) mice. Multivariate analysis revealed unique metabolomic signatures for M-CK(
      /-) and M-CK/ScCKmit(-/-) hearts suggesting that rearrangements in
      phosphotransfer and substrate utilization networks provide compensation for
      genetic CK deficiency. This new information highlights the significance of
      integrated CK-, AK-, guanine nucleotide- and glycolytic enzyme-catalysed
      phosphotransfer networks in supporting the adaptivity and robustness of the
      cellular energetic system.

PMID- 21878524
TI  - Ligand stoichiometry of the cold- and menthol-activated channel TRPM8.
AB  - Temperature-sensitive transient receptor potential (TRP) channels play a key role
      in somatosensation, not only as primary thermosensors but also as chemosensors
      for various compounds that evoke a thermal sensation. The fundamental mechanisms
      whereby TRP channels translate ligand binding into opening of the ion conducting
      pore are, however, poorly understood, and the actual number of ligands that bind
      to these channels is fully unknown. Here, we investigated the ligand
      stoichiometry of the cold sensor and menthol receptor TRPM8. Based on a detailed
      biophysical analysis of tandem constructs of wild-type and menthol-insensitive
      TRPM8 subunits, we now provide direct evidence that each channel has four
      independent and energetically equivalent menthol interaction sites. These results
      suggest a fundamentally different ligand stoichiometry in TRP channels, in
      comparison with other major families of ligand-gated ion channels.

PMID- 21878523
TI  - Endothelin-converting enzyme-1 regulates trafficking and signalling of the
      neurokinin 1 receptor in endosomes of myenteric neurones.
AB  - Neuropeptide signalling at the plasma membrane is terminated by neuropeptide
      degradation by cell-surface peptidases, and by beta-arrestin-dependent receptor
      desensitization and endocytosis. However, receptors continue to signal from
      endosomes by beta-arrestin-dependent processes, and endosomal sorting mediates
      recycling and resensitization of plasma membrane signalling. The mechanisms that
      control signalling and trafficking of receptors in endosomes are poorly defined.
      We report a major role for endothelin-converting enzyme-1 (ECE-1) in controlling
      substance P (SP) and the neurokinin 1 receptor (NK(1)R) in endosomes of myenteric
      neurones. ECE-1 mRNA and protein were expressed by myenteric neurones of rat and
      mouse intestine. SP (10 nM, 10 min) induced interaction of NK(1)R and beta
      arrestin at the plasma membrane, and the SP-NK(1)R-beta-arrestin signalosome
      complex trafficked by a dynamin-mediated mechanism to ECE-1-containing early
      endosomes, where ECE-1 can degrade SP. After 120 min, NK(1)R recycled from
      endosomes to the plasma membrane. ECE-1 inhibitors (SM-19712, PD-069185) and the
      vacuolar H(+)ATPase inhibitor bafilomycin A(1), which prevent endosomal SP
      degradation, suppressed NK(1)R recycling by >50%. Preincubation of neurones with
      SP (10 nM, 5 min) desensitized Ca(2+) transients to a second SP challenge after
      10 min, and SP signals resensitized after 60 min. SM-19712 inhibited NK(1)R
      resensitization by >90%. ECE-1 inhibitors also caused sustained SP-induced
      activation of extracellular signal-regulated kinases, consistent with
      stabilization of the SP-NK(1)R-beta-arrestin signalosome. By degrading SP and
      destabilizing endosomal signalosomes, ECE-1 has a dual role in controlling
      endocytic signalling and trafficking of the NK(1)R: promoting resensitization of
      G protein-mediated plasma membrane signalling, and terminating beta-arrestin
      mediated endosomal signalling.

PMID- 21878525
TI  - Orai channel-dependent activation of phospholipase C-delta: a novel mechanism for
      the effects of calcium entry on calcium oscillations.
AB  - The frequency of oscillatory Ca(2+) signals is a major determinant in the
      selective activation of discrete downstream responses in non-excitable cells. An
      important modulator of this oscillation frequency is known to be the rate of
      agonist-activated Ca(2+) entry. However precisely how this is achieved and the
      respective roles of store-operated versus store-independent Ca(2+) entry pathways
      in achieving this are unclear. Here, we examine the possibility that a direct
      stimulation of a phospholipase C (PLC) by the entering Ca(2+) can induce a
      modulation of Ca(2+) oscillation frequency, and examine the roles of the
      endogenous store-operated and store-independent Orai channels (CRAC and ARC
      channels, respectively) in such a mechanism. Using the decline in the magnitude
      of currents through expressed PIP(2)-dependent Kir2.1 channels as a sensitive
      assay for PLC activity, we show that simple global increases in Ca(2+)
      concentrations over the physiological range do not significantly affect PLC
      activity. Similarly, maximal activation of endogenous CRAC channels also fails to
      affect PLC activity. In contrast, equivalent activation of endogenous ARC
      channels resulted in a 10-fold increase in the measured rate of PIP(2) depletion.
      Further experiments show that this effect is strictly dependent on the Ca(2+)
      entering via these channels, rather than the gating of the channels or the
      arachidonic acid used to activate them, and that it reflects the activation of a
      PLCdelta by local Ca(2+) concentrations immediately adjacent to the active
      channels. Finally, based on the effects of expression of either a dominant
      negative mutant Orai3 that is an essential component of the ARC channel, or a
      catalytically compromised mutant PLCdelta, it was shown that this specific action
      of the store-independent ARC channel-mediated Ca(2+) entry on PLCdelta has a
      significant impact on the oscillation frequency of the Ca(2+) signals activated
      by low concentrations of agonist.

PMID- 21878526
TI  - Kinetic changes in tetanic Ca2+ transients in enzymatically dissociated muscle
      fibres under repetitive stimulation.
AB  - We used enzymatically dissociated flexor digitorum brevis (FDB) and soleus fibres
      loaded with the fast Ca(2+) dye Magfluo-4 AM, and adhered to Laminin, to test
      whether repetitive stimulation induces progressive changes in the kinetics of
      Ca(2+) release and reuptake in a fibre-type-dependent fashion. We applied a
      protocol of tetani of 350 ms, 100 Hz, every 4 s to reach a mean amplitude
      reduction of 25% of the first peak. Morphology type I (MT-I) and morphology type
      II (MT-II) fibres underwent a total of 96 and 52.8 tetani (P < 0.01 between
      groups), respectively. The MT-II fibres (n = 18) showed significant reductions of
      the amplitude (19%), an increase in rise time (8.5%) and a further reduction of
      the amplitude/rise time ratio (25.5%) of the first peak of the tetanic transient
      after 40 tetani, while MT-I fibres (n = 5) did not show any of these changes.
      However, both fibre types showed significant reductions in the maximum rate of
      rise of the first peak after 40 tetani. Two subpopulations among the MT-II fibres
      could be distinguished according to Ca(2+) reuptake changes. Fast-fatigable MT-II
      fibres (fMT-II) showed an increase of 32.2% in the half-width value of the first
      peak, while for fatigue-resistant MT-II fibres (rMT-II), the increase amounted to
      6.9%, both after 40 tetani. Significant and non-significant increases of 36.4%
      and 11.9% in the first time constant of decay (t(1)) values were seen after 40
      tetani in fMT-II and rMT-II fibres, respectively. MT-I fibres did not show
      kinetic changes in any of the Ca(2+) reuptake variables. All changes were
      reversed after an average recovery of 7.5 and 15.4 min for MT-I and MT-II fibres,
      respectively. Further experiments ruled out the possibility that the differences
      in the kinetic changes of the first peak of the Ca(2+) transients between fibres
      MT-I and MT-II could be related to the inactivation of Ca(2+) release mechanism.
      In conclusion, we established a model of enzymatically dissociated fibres, loaded
      with Magfluo-4 and adhered to Laminin, to study muscle fatigue and demonstrated
      fibre-type-dependent, fatigue-induced kinetic changes in both Ca(2+) release and
      reuptake.

PMID- 21878527
TI  - Xamoterol impairs hippocampus-dependent emotional memory retrieval via Gi/o
      coupled beta2-adrenergic signaling.
AB  - Xamoterol, a partial beta(1)-adrenergic receptor agonist, has been reported to
      impair the retrieval of hippocampus-dependent spatial reference memory in rats.
      In contrast, xamoterol restores memory retrieval in gene-targeted mice lacking
      norepinephrine (NE) and in a transgenic mouse model of Down syndrome in which NE
      levels are reduced. Restoration of retrieval by xamoterol in these two models
      complements the observation that NE and beta(1) signaling are required for
      hippocampus-dependent retrieval of contextual and spatial reference memory in
      wild-type mice and rats. Additional evidence indicates that cAMP-mediated PKA and
      Epac signaling are required for the retrieval of hippocampus-dependent memory. As
      a result, we hypothesized that xamoterol has effects in addition to the
      stimulation of beta(1) receptors that, at higher doses, act to counter the
      effects of beta(1) signaling. Here we report that xamoterol-induced disruption of
      memory retrieval depends on beta(2)-adrenergic receptor signaling. Interestingly,
      the impairment of memory retrieval by xamoterol is blocked by pretreatment with
      pertussis toxin, an uncoupling agent for G(i/o) signaling, suggesting that
      beta(2) signaling opposes beta(1) signaling during memory retrieval at the level
      of G protein and cAMP signaling. Finally, similar to the time-dependent roles for
      NE, beta(1), and cAMP signaling in hippocampus-dependent memory retrieval,
      xamoterol only impairs retrieval for several days after training, indicating that
      its effects are also limited by the age of the memory. We conclude that the
      disruption of memory retrieval by xamoterol is mediated by G(i/o)-coupled beta(2)
      signaling, which opposes the G(s)-coupled beta(1) signaling that is transiently
      required for hippocampus-dependent emotional memory retrieval.

PMID- 21878528
TI  - Running is the neurogenic and neurotrophic stimulus in environmental enrichment.
AB  - Environmental enrichment (EE) increases dentate gyrus (DG) neurogenesis and brain
      derived neurotrophic factor (BDNF) levels. However, running is considered an
      element of EE. To dissociate effects of physical activity and enrichment on
      hippocampal neurogenesis and BDNF levels, young female C57Bl/6 mice were housed
      under control, running, enrichment, or enrichment plus running conditions, and
      injected with bromodeoxyuridine. Cell genesis was assessed after 12 d and
      differentiation was analyzed 1 mo later. In addition, locomotor activity in the
      open field and hippocampal mature BDNF peptide levels were measured. Open-field
      adaptation was improved in all groups, compared to controls, but more so with
      running. New cell proliferation, survival, neuron number, and neurotrophin levels
      were enhanced only when running was accessible. We conclude that exercise is the
      critical factor mediating increased BDNF levels and adult hippocampal
      neurogenesis.

PMID- 21878529
TI  - TLR9 agonists oppositely modulate DNA repair genes in tumor versus immune cells
      and enhance chemotherapy effects.
AB  - Synthetic oligodeoxynucleotides expressing CpG motifs (CpG-ODN) are a Toll-like
      receptor 9 (TLR9) agonist that can enhance the antitumor activity of DNA-damaging
      chemotherapy and radiation therapy in preclinical mouse models. We hypothesized
      that the success of these combinations is related to the ability of CpG-ODN to
      modulate genes involved in DNA repair. We conducted an in silico analysis of
      genes implicated in DNA repair in data sets obtained from murine colon carcinoma
      cells in mice injected intratumorally with CpG-ODN and from splenocytes in mice
      treated intraperitoneally with CpG-ODN. CpG-ODN treatment caused downregulation
      of DNA repair genes in tumors. Microarray analyses of human IGROV-1 ovarian
      carcinoma xenografts in mice treated intraperitoneally with CpG-ODN confirmed in
      silico findings. When combined with the DNA-damaging drug cisplatin, CpG-ODN
      significantly increased the life span of mice compared with individual
      treatments. In contrast, CpG-ODN led to an upregulation of genes involved in DNA
      repair in immune cells. Cisplatin-treated patients with ovarian carcinoma as well
      as anthracycline-treated patients with breast cancer who are classified as "CpG
      like" for the level of expression of CpG-ODN modulated DNA repair genes have a
      better outcome than patients classified as "CpG-untreated-like," indicating the
      relevance of these genes in the tumor cell response to DNA-damaging drugs. Taken
      together, the findings provide evidence that the tumor microenvironment can
      sensitize cancer cells to DNA-damaging chemotherapy, thereby expanding the
      benefits of CpG-ODN therapy beyond induction of a strong immune response.

PMID- 21878530
TI  - Antiangiogenic agent sunitinib transiently increases tumor oxygenation and
      suppresses cycling hypoxia.
AB  - Structural and functional abnormalities in tumor blood vessels impact the
      delivery of oxygen and nutrients to solid tumors, resulting in chronic and
      cycling hypoxia. Although chronically hypoxic regions exhibit treatment
      resistance, more recently it has been shown that cycling hypoxic regions acquire
      prosurvival pathways. Angiogenesis inhibitors have been shown to transiently
      normalize the tumor vasculatures and enhance tumor response to treatments.
      However, the effect of antiangiogenic therapy on cycling tumor hypoxia remains
      unknown. Using electron paramagnetic resonance imaging and MRI in tumor-bearing
      mice, we have examined the vascular renormalization process by longitudinally
      mapping tumor partial pressure of oxygen (pO(2)) and microvessel density during
      treatments with a multi-tyrosine kinase inhibitor sunitinib. Transient
      improvement in tumor oxygenation was visualized by electron paramagnetic
      resonance imaging 2 to 4 days following antiangiogenic treatments, accompanied by
      a 45% decrease in microvessel density. Radiation treatment during this time
      period of improved oxygenation by antiangiogenic therapy resulted in a
      synergistic delay in tumor growth. In addition, dynamic oxygen imaging obtained
      every 3 minutes was conducted to distinguish tumor regions with chronic and
      cycling hypoxia. Sunitinib treatment suppressed the extent of temporal
      fluctuations in tumor pO(2) during the vascular normalization window, resulting
      in the decrease of cycling tumor hypoxia. Overall, the findings suggest that
      longitudinal and noninvasive monitoring of tumor pO(2) makes it possible to
      identify a window of vascular renormalization to maximize the effects of
      combination therapy with antiangiogenic drugs.

PMID- 21878535
TI  - Randomized phase II trial of letrozole plus anti-MUC1 antibody AS1402 in hormone
      receptor-positive locally advanced or metastatic breast cancer.
AB  - PURPOSE: AS1402 is a humanized immunoglobulin G1 antibody that targets the
      aberrantly glycosylated antigen MUC1, which is overexpressed in 90% of breast
      tumors and contributes to estrogen-mediated growth and survival of breast cancer
      cells in vitro by modulating estrogen receptor (ER) activity. Aromatase
      inhibitors have been reported to enhance antibody-dependent cell-mediated
      cytotoxicity elicited by antibodies in vitro. We compared the outcomes of
      patients with breast cancer treated with letrozole with or without AS1402.
      EXPERIMENTAL DESIGN: The study population included 110 patients with locally
      advanced or metastatic hormone receptor-positive breast cancer randomized to
      receive 2.5 mg letrozole only once daily or with a weekly 9 mg/kg AS1402
      infusion. The primary endpoint was overall response rate. Secondary endpoints
      included progression-free survival, time to progression, and safety. AS1402
      exposure and influence of allotypes of FcgammaRIIIa, FcgammaRIIa, and MUC1 were
      evaluated. RESULTS: The study was stopped early because of a trend toward worse
      response rates and a higher rate of early disease progression in the AS1402 +
      letrozole arm. Final analysis revealed no significant difference in efficacy
      between the study arms. Evaluated gene polymorphisms did not define patient
      subgroups with improved outcomes. Addition of AS1402 to letrozole was associated
      with manageable toxicity. CONCLUSIONS: Because adding AS1402 to letrozole did not
      improve outcomes compared with letrozole only, blocking ER may be a better
      strategy for harnessing MUC1 modulation of the ER to a clinical advantage.
      FcgammaRIIIa, FcgammaRIIa, and MUC1 allotype did not predict outcome for patients
      treated with letrozole with or without AS1402.

PMID- 21878536
TI  - PTEN protein loss by immunostaining: analytic validation and prognostic indicator
      for a high risk surgical cohort of prostate cancer patients.
AB  - PURPOSE: Analytically validated assays to interrogate biomarker status in
      clinical samples are crucial for personalized medicine. PTEN is a tumor
      suppressor commonly inactivated in prostate cancer that has been mechanistically
      linked to disease aggressiveness. Though deletion of PTEN, as detected by
      cumbersome FISH spot counting assays, is associated with poor prognosis, few
      studies have validated immunohistochemistry (IHC) assays to determine whether
      loss of PTEN protein is associated with unfavorable disease. EXPERIMENTAL DESIGN:
      PTEN IHC was validated by employing formalin fixed and paraffin-embedded isogenic
      human cell lines containing or lacking intact PTEN alleles. PTEN IHC was 100%
      sensitive and 97.8% specific for detecting genomic alterations in 58 additional
      cell lines. PTEN protein loss was then assessed on 376 prostate tumor samples,
      and PTEN FISH or high resolution single nucleotide polymorphism microarray
      analysis was done on a subset of these cases. RESULTS: PTEN protein loss, as
      assessed as a dichotomous IHC variable, was highly reproducible, correlated
      strongly with adverse pathologic features (e.g., Gleason score and pathologic
      stage), detected between 75% and 86% of cases with PTEN genomic loss, and was
      found at times in the absence of apparent genomic loss. In a cohort of 217 high
      risk surgically treated patients, PTEN protein loss was associated with decreased
      time to metastasis. CONCLUSION: These studies validate a simple method to
      interrogate PTEN status in clinical specimens and support the utility of this
      test in future multicenter studies, clinical trials, and ultimately perhaps for
      routine clinical care.

PMID- 21878537
TI  - The novel chemical entity YTR107 inhibits recruitment of nucleophosmin to sites
      of DNA damage, suppressing repair of DNA double-strand breaks and enhancing
      radiosensitization.
AB  - PURPOSE: Radiation therapy continues to be an important therapeutic strategy for
      providing definitive local/regional control of human cancer. However, oncogenes
      that harbor driver mutations and/or amplifications can compromise therapeutic
      efficacy. Thus, there is a need for novel approaches that enhance the DNA damage
      produced by ionizing radiation. EXPERIMENTAL DESIGN: A forward chemical genetic
      approach coupled with cell-based phenotypic screening of several tumor cell lines
      was used to identify a novel chemical entity (NCE) that functioned as a radiation
      sensitizer. Proteomics, comet assays, confocal microscopy, and immunoblotting
      were used to identify the biological target. RESULTS: The screening process
      identified a 5-((N-benzyl-1H-indol-3-yl)-methylene)pyrimidine
      2,4,6(1H,3H,5H)trione as an NCE that radiosensitized cancer cells expressing
      amplified and/or mutated RAS, ErbB, PIK3CA, and/or BRAF oncogenes. Affinity-based
      solid-phase resin capture followed by liquid chromatography/tandem mass
      spectrometry identified the chaperone nucleophosmin (NPM) as the NCE target.
      SiRNA suppression of NPM abrogated radiosensitization by the NCE. Confocal
      microscopy showed that the NCE inhibited NPM shuttling to radiation-induced DNA
      damage repair foci, and the analysis of comet assays indicated a diminished rate
      of DNA double-strand break repair. CONCLUSION: These data support the hypothesis
      that inhibition of DNA repair due to inhibition of NPM shuttling increases the
      efficacy of DNA-damaging therapeutic strategies.

PMID- 21878539
TI  - SNPs and Haplotypes in DPYD and Outcome of Capecitabine-Letter.

PMID- 21878538
TI  - Dicer-mediated upregulation of BCRP confers tamoxifen resistance in human breast
      cancer cells.
AB  - PURPOSE: Tamoxifen (Tam) is the most prescribed hormonal agent for treatment of
      estrogen receptor alpha (ERalpha)-positive breast cancer patients. Using
      microarray analysis, we observed that metastatic breast tumors resistant to Tam
      therapy had elevated levels of Dicer. EXPERIMENTAL DESIGN: We overexpressed Dicer
      in ERalpha-positive MCF-7 human breast cancer cells and observed a concomitant
      increase in expression of the breast cancer resistance protein (BCRP). We thus
      hypothesized that Tam resistance associated with Dicer overexpression in ERalpha
      positive breast cancer cells may involve BCRP. We analyzed BCRP function in Dicer
      overexpressing cells using growth in soft agar and mammosphere formation and
      evaluated intracellular Tam efflux. RESULTS: In the presence of Tam, Dicer
      overexpressing cells formed resistant colonies in soft agar, and treatment with
      BCRP inhibitors restored Tam sensitivity. Tumor xenograft studies confirmed that
      Dicer-overexpressing cells were resistant to Tam in vivo. Tumors and distant
      metastases could be initiated with as few as five mammosphere cells from both
      vector and Dicer-overexpressing cells, indicating that the mammosphere assay
      selected for cells with enhanced tumor-initiating and metastatic capacity. Dicer
      overexpressing cells with elevated levels of BCRP effluxed Tam more efficiently
      than control cells, and BCRP inhibitors were able to inhibit efflux. CONCLUSION:
      Dicer-overexpressing breast cancer cells enriched for cells with enhanced BCRP
      function. We hypothesize that it is this population which may be involved in the
      emergence of Tam-resistant growth. BCRP may be a novel clinical target to restore
      Tam sensitivity.

PMID- 21878541
TI  - SNPs and haplotypes in DPYD and outcome of capecitabine--Letter.

PMID- 21878542
TI  - Modulating impact of human chorionic gonadotropin hormone on the maturation and
      function of hematopoietic cells.
AB  - hCG hormone is a naturally occurring, immune-modulating agent, which is highly
      expressed during pregnancy and causes improvements of some autoimmune diseases
      such as multiple sclerosis and Crohn's disease. Little is known about its immune
      modulating effects. This study in MNCs of women who received hCG as
      preconditioning prior to IVF demonstrates that hCG increases anti-inflammatory IL
      27 expression and reduces inflammatory IL-17 expression. In addition, we found
      increased IL-10 levels and elevated numbers of Tregs in peripheral blood of women
      after hCG application. Rejection of allogeneic skin grafts was delayed in female
      mice receiving hCG. We conclude that hCG may be useful for the induction of
      immune tolerance in solid organ transplantation.

PMID- 21878543
TI  - Defective eosinophil hematopoiesis ex vivo in inbred Rocky Mountain White (IRW)
      mice.
AB  - We examine the proliferation and differentiation of bone marrow (BM) progenitors
      from inbred Rocky Mountain White (IRW) mice, a strain used primarily for
      retrovirus infection studies. In contrast to findings with BALB/c and C57BL/6
      strains, IRW BM cells cannot proliferate or generate pure eosinophil cultures ex
      vivo in response to a defined cytokine regimen. Analysis of IRW BM at baseline
      was unremarkable, including 0.08 +/- 0.03% Lin(-)Sca-1(+)c-kit(+) (LSK)
      hematopoietic stem cells and 5.2 +/- 0.3% eosinophils; the percentage of
      eosinophil progenitors (EoPs; Lin(-)Sca-1(-)c-kit(+)CD34(+)IL-5Ralpha(+)) was
      similar in all three mouse strains. Transcripts encoding GM-CSFRalpha and the IL
      3/IL-5/GM-CSF common beta chain were detected at equivalent levels in IRW and
      BALB/c BM, whereas expression of transcripts encoding IL-5Ralpha, IL-3Ralpha, and
      GATA-2 was diminished in IRW BM compared with BALB/c. Expression of membrane
      bound IL-5Ralpha and intracellular STAT5 proteins was also diminished in IRW BM
      cells. Diminished expression of transcripts encoding IL-5Ralpha and GATA-2 and
      immunoreactive STAT5 in IRW BM persisted after 4 days in culture, along with
      diminished expression of GATA-1. Western blot revealed that cells from IRW BM
      overexpress nonsignaling soluble IL-5Ralpha protein. Interestingly, OVA
      sensitization and challenge resulted in BM and airway eosinophilia in IRW mice;
      however, the responses were significantly blunted. These results suggest that IRW
      mice have diminished capacity to generate eosinophils in culture and in vivo,
      likely as a result of diminished signaling via IL-5Ralpha.

PMID- 21878545
TI  - Inhibitory effect of semaphorin-3A, a known axon guidance molecule, in the human
      thymocyte migration induced by CXCL12.
AB  - Intrathymic T cell differentiation takes place within the thymic lobules and
      depends on interactions between developing thymocytes and cells of the thymic
      microenvironment. Along with differentiation, thymocytes migrate in an oriented
      progression, which is tightly regulated by a number of interactions, including
      one mediated by the chemokine CXCL12. It has been shown recently that SEMA-3A, a
      soluble member of the semaphorin family, is also involved in this human thymocyte
      migration and can have a chemorepulsive and de-adhesive role. Herein, we study
      the role of SEMA-3A on the CXCL12-driven migration of human thymocytes. We have
      shown that SEMA-3A is able to inhibit the chemotaxis triggered by CXCL12. Such an
      inhibition was seen in respect to immature and mature CD4/CD8-defined thymocyte
      subsets and can be reverted specifically by neutralizing anti-SEMA-3A mAb. We
      have also shown that SEMA-3A consistently down-regulates CXCR4 membrane
      expression in all CD4/CD8-defined thymocyte subsets, and this down-regulation is
      accompanied by a decrease in the phosphorylation of FAK and ZAP-70 protein
      kinases. Taken together, these results demonstrate the involvement of SEMA-3A in
      the regulation of CXCL12-driven human thymocyte migration, where it acts as a
      physiological antagonist.

PMID- 21878544
TI  - Macrophage phagocytosis: effects of environmental pollutants, alcohol, cigarette
      smoke, and other external factors.
AB  - The ability of a pathogen to evade host immunity successfully, in contrast to the
      host's capacity to defend itself against a foreign invader, is a complex
      struggle, in which eradication of infection is dictated by a robust immunologic
      response. Often, there are external factors that can alter the outcome by tipping
      the scale to benefit pathogen establishment rather than resolution by the host's
      defense system. These external sources, such a cigarettes, alcohol, or
      environmental pollutants, can negatively influence the effectiveness of the
      immune system's response to a pathogen. The observed suppression of immune
      function can be attributed to dysregulated cytokine and chemokine production, the
      loss of migratory potential, or the inability to phagocytose pathogens by immune
      cells. This review will focus on the mechanisms involved during the toxin-induced
      suppression of phagocytosis. The accumulated data support the importance of
      studying the mechanisms of phagocytosis following exposure to these factors, in
      that this effect alone cannot only leave the host susceptible to infection but
      also promote alterations in many other macrophage functions necessary for
      pathogen clearance and restoration of homeostasis.

PMID- 21878546
TI  - Interactions of a Pop5/Rpp1 heterodimer with the catalytic domain of RNase MRP.
AB  - Ribonuclease (RNase) MRP is a multicomponent ribonucleoprotein complex closely
      related to RNase P. RNase MRP and eukaryotic RNase P share most of their protein
      components, as well as multiple features of their catalytic RNA moieties, but
      have distinct substrate specificities. While RNase P is practically universally
      found in all three domains of life, RNase MRP is essential in eukaryotes. The
      structural organizations of eukaryotic RNase P and RNase MRP are poorly
      understood. Here, we show that Pop5 and Rpp1, protein components found in both
      RNase P and RNase MRP, form a heterodimer that binds directly to the conserved
      area of the putative catalytic domain of RNase MRP RNA. The Pop5/Rpp1 binding
      site corresponds to the protein binding site in bacterial RNase P RNA. Structural
      and evolutionary roles of the Pop5/Rpp1 heterodimer in RNases P and MRP are
      discussed.

PMID- 21878547
TI  - Argonaute protein identity and pairing geometry determine cooperativity in
      mammalian RNA silencing.
AB  - Small RNAs loaded into Argonaute proteins direct silencing of complementary
      target mRNAs. It has been proposed that multiple, imperfectly complementary small
      interfering RNAs or microRNAs, when bound to the 3' untranslated region of a
      target mRNA, function cooperatively to silence target expression. We report that,
      in cultured human HeLa cells and mouse embryonic fibroblasts, Argonaute1 (Ago1),
      Ago3, and Ago4 act cooperatively to silence both perfectly and partially
      complementary target RNAs bearing multiple small RNA-binding sites. Our data
      suggest that for Ago1, Ago3, and Ago4, multiple, adjacent small RNA-binding sites
      facilitate cooperative interactions that stabilize Argonaute binding. In
      contrast, small RNAs bound to Ago2 and pairing perfectly to an mRNA target act
      independently to silence expression. Noncooperative silencing by Ago2 does not
      require the endoribonuclease activity of the protein: A mutant Ago2 that cannot
      cleave its mRNA target also silences noncooperatively. We propose that Ago2 binds
      its targets by a mechanism fundamentally distinct from that used by the three
      other mammalian Argonaute proteins.

PMID- 21878548
TI  - The crystal structure of an oligo(U):pre-mRNA duplex from a trypanosome RNA
      editing substrate.
AB  - Guide RNAs bind antiparallel to their target pre-mRNAs to form editing substrates
      in reaction cycles that insert or delete uridylates (Us) in most mitochondrial
      transcripts of trypanosomes. The 5' end of each guide RNA has an anchor sequence
      that binds to the pre-mRNA by base-pair complementarity. The template sequence in
      the middle of the guide RNA directs the editing reactions. The 3' ends of most
      guide RNAs have ~15 contiguous Us that bind to the purine-rich unedited pre-mRNA
      upstream of the editing site. The resulting U-helix is rich in G.U wobble base
      pairs. To gain insights into the structure of the U-helix, we crystallized 8 bp
      of the U-helix in one editing substrate for the A6 mRNA of Trypanosoma brucei.
      The fragment provides three samples of the 5'-AGA-3'/5'-UUU-3' base-pair triple.
      The fusion of two identical U-helices head-to-head promoted crystallization. We
      obtained X-ray diffraction data with a resolution limit of 1.37 A. The U-helix
      had low and high twist angles before and after each G.U wobble base pair; this
      variation was partly due to shearing of the wobble base pairs as revealed in
      comparisons with a crystal structure of a 16-nt RNA with all Watson-Crick base
      pairs. Both crystal structures had wider major grooves at the junction between
      the poly(U) and polypurine tracts. This junction mimics the junction between the
      template helix and the U-helix in RNA-editing substrates and may be a site of
      major groove invasion by RNA editing proteins.

PMID- 21878549
TI  - The first two nucleotides of the respiratory syncytial virus antigenome RNA
      replication product can be selected independently of the promoter terminus.
AB  - There is limited knowledge regarding how the RNA-dependent RNA polymerases of the
      nonsegmented negative-strand RNA viruses initiate genome replication. In a
      previous study of respiratory syncytial virus (RSV) RNA replication, we found
      evidence that the polymerase could select the 5'-ATP residue of the genome RNA
      independently of the 3' nucleotide of the template. To investigate if a similar
      mechanism is used during antigenome synthesis, a study of initiation from the RSV
      leader (Le) promoter was performed using an intracellular minigenome assay in
      which RNA replication was restricted to a single step, so that the products
      examined were derived only from input mutant templates. Templates in which Le
      nucleotides 1U, or 1U and 2G, were deleted directed efficient replication, and in
      both cases, the replication products were initiated at the wild-type position, at
      position -1 or -2 relative to the template, respectively. Sequence analysis of
      the RNA products showed that they contained ATP and CTP at the -1 and -2
      positions, respectively, thus restoring the mini-antigenome RNA to wild-type
      sequence. These data indicate that the RSV polymerase is able to select the first
      two nucleotides of the antigenome and initiate at the correct position, even if
      the 3'-terminal two nucleotides of the template are missing. Substitution of
      positions +1 and +2 of the template reduced RNA replication and resulted in
      increased initiation at positions +3 and +5. Together these data suggest a model
      for how the RSV polymerase initiates antigenome synthesis.

PMID- 21878551
TI  - Modern imaging techniques during therapy in patients with multiple myeloma.
AB  - Imaging modalities used in the diagnosis of multiple myeloma have evolved and
      most of them are also suitable for either early or mid-term monitoring of
      response to novel antimyeloma therapy. This pictorial essay focuses on modern
      imaging techniques for diagnosis and follow-up of patients with multiple myeloma
      in order to highlight their individual strengths and limitations. Also, the
      impact of recently established modern pharmaceutical therapy, like anti
      angiogenic medication, on the tumor is addressed.

PMID- 21878552
TI  - Dietary salt exacerbates isoproterenol-induced cardiomyopathy in rats.
AB  - Spontaneously hypertensive heart failure rats (SHHFs) take longer to develop
      compensated heart failure (HF) and congestive decompensation than common surgical
      models of HF. Isoproterenol (ISO) infusion can accelerate cardiomyopathy in young
      SHHFs, while dietary salt loading in hypertensive rats induces cardiac fibrosis,
      hypertrophy, and--in a minority-congestive HF. By combining ISO with dietary salt
      loading in young SHHFs, the authors sought a nonsurgical model that is more time-
      and resource-efficient than any of these factors alone. The authors hypothesized
      that salt loading would enhance ISO-accelerated cardiomyopathy, promoting
      fibrosis, hypertrophy, and biochemical characteristics of HF. SHHFs (lean male,
      90d) were infused for 4 wk with ISO (2.5 mg/kg/day) or saline. After 2 wk of
      infusion, a 6-wk high-salt diet (4%, 6%, or 8% NaCl) was initiated. Eight percent
      salt increased heart weight, HF markers (plasma B-type natriuretic peptide, IL
      6), lung lymphocytes, and indicators of lung injury and edema (albumin and
      protein) relative to control diet, while increasing urine pro-atrial natriuretic
      peptide relative to ISO-only. High salt also exacerbated ISO-cardiomyopathy and
      fibrosis. Thus, combining ISO infusion with dietary salt loading in SHHFs holds
      promise for a new rat HF model that may help researchers to elucidate HF
      mechanisms and unearth effective treatments.

PMID- 21878553
TI  - Hyaline glomerulopathy with tubulo-fibrillary deposits in young ddY mice.
AB  - Hyaline glomerulopathy with tubulo-fibrillary deposits was observed in two young
      female ddY mice. One of the mice showed gross systemic edema and bilateral
      enlargement and pale color of the kidneys, whereas no significant gross findings
      were noted in the other mouse. Microscopically, a large number of the glomeruli
      in both mice were enlarged because of diffuse and global deposition of amorphous
      eosinophilic materials. The deposits were negatively stained with Congo red and
      positively stained with IgG, IgM, IgA, C3, and periodic acid-Schiff. Electron
      microscopic examination revealed microtubular and fibrillary deposits with
      diameters of 80-100 and 9-16 nm, respectively, in the subendothelial space of the
      glomeruli. These features are histopathologically similar to immunotactoid
      glomerulopathy or fibrillary glomerulonephritis according to the classification
      of human glomerular lesions. Understanding of these characteristics of hyaline
      glomerulopathy in ddY mice is essential when evaluating pharmacological,
      pharmacokinetic, and toxicological studies using this mouse strain.

PMID- 21878550
TI  - Soybean homologs of MPK4 negatively regulate defense responses and positively
      regulate growth and development.
AB  - Mitogen-activated protein kinase (MAPK) cascades play important roles in disease
      resistance in model plant species such as Arabidopsis (Arabidopsis thaliana) and
      tobacco (Nicotiana tabacum). However, the importance of MAPK signaling pathways
      in the disease resistance of crops is still largely uninvestigated. To better
      understand the role of MAPK signaling pathways in disease resistance in soybean
      (Glycine max), 13, nine, and 10 genes encoding distinct MAPKs, MAPKKs, and
      MAPKKKs, respectively, were silenced using virus-induced gene silencing mediated
      by Bean pod mottle virus. Among the plants silenced for various MAPKs, MAPKKs,
      and MAPKKKs, those in which GmMAPK4 homologs (GmMPK4s) were silenced displayed
      strong phenotypes including stunted stature and spontaneous cell death on the
      leaves and stems, the characteristic hallmarks of activated defense responses.
      Microarray analysis showed that genes involved in defense responses, such as
      those in salicylic acid (SA) signaling pathways, were significantly up-regulated
      in GmMPK4-silenced plants, whereas genes involved in growth and development, such
      as those in auxin signaling pathways and in cell cycle and proliferation, were
      significantly down-regulated. As expected, SA and hydrogen peroxide accumulation
      was significantly increased in GmMPK4-silenced plants. Accordingly, GmMPK4
      silenced plants were more resistant to downy mildew and Soybean mosaic virus
      compared with vector control plants. Using bimolecular fluorescence
      complementation analysis and in vitro kinase assays, we determined that GmMKK1
      and GmMKK2 might function upstream of GmMPK4. Taken together, our results
      indicate that GmMPK4s negatively regulate SA accumulation and defense response
      but positively regulate plant growth and development, and their functions are
      conserved across plant species.

PMID- 21878554
TI  - Renal toxicity of lisinopril and rosuvastatin, alone and in combination, in
      Wistar rats.
AB  - The aim of study was to evaluate the effect of commonly used lisinopril,
      rosuvastatin and their combined action on site-specific nephrotoxicity in rats
      using clusterin and microalbumin nephrotoxic biomarkers and other related
      parameters using oral gavage. Rosuvastatin at 2 different doses showed increase
      in urinary microalbumin levels whereas lisinopril and its combination with
      rosuvastatin at 2 different doses did not show urinary microalbumin excretion
      indicating beneficial effects of lisinopril in terms of reducing microalbumin.
      Urinary clusterin levels significantly increased in high-dose treated animals of
      lisinopril and rosuvastatin. The use of lisinopril plus rosuvastatin at low dose
      also led to worsened renal function by raising urinary clusterin levels (217 +/-
      4.6 ng/ml) when compared with the control (143 +/- 3.3 ng/ml). Renal
      histopathology showed multifocal regeneration of tubules indicating proximal
      tubule damaged. These results indicate that lisinopril (50 mg/kg), rosuvastatin
      (100 mg/kg), lisinopril+rosuvastatin (20+40 mg/kg) and lisinopril+rosuvastatin
      (50+100 mg/kg) showed toxicity only on proximal tubules.

PMID- 21878555
TI  - The role of the toxicologic pathologist in the biopharmaceutical industry.
AB  - Toxicologic pathologists contribute significantly to the development of new
      biopharmaceuticals, yet there is often a lack of awareness of this specialized
      role. As the members of multidisciplinary teams, toxicologic pathologists
      participate in all aspects of the drug development process. This review is part
      of an initiative by the Society of Toxicologic Pathology to educate scientists
      about toxicologic pathology and to attract junior scientists, veterinary
      students, and veterinarians into the field. We describe the role of toxicologic
      pathologists in identifying candidate agents, elucidating bioactive pathways, and
      evaluating efficacy and toxicity in preclinical animal models. Educational and
      specialized training requirements and the challenges of working in a global
      environment are discussed. The biopharmaceutical industry provides diverse,
      challenging, and rewarding career opportunities in toxicologic pathology. We hope
      that this review promotes understanding of the important role the toxicologic
      pathologist plays in drug development and encourages exploration of an important
      career option.

PMID- 21878556
TI  - Paving asphalt products exhibit a lack of carcinogenic and mutagenic activity.
AB  - A paving asphalt and a vacuum residuum (derived from crude oil by atmospheric and
      subsequent vacuum distillation and used as a blend stock for asphalt) were tested
      in skin carcinogenesis assays in mice and in optimized Ames assays for mutagenic
      activity. In the skin cancer tests, each substance was applied twice weekly for
      104 weeks to the clipped backs of groups of 50 male C3H mice. Neither the paving
      asphalt nor the vacuum residuum (30% weight/volume and 75% weight/weight in US
      Pharmacopeia mineral oil, respectively) produced any tumors. The positive control
      benzo[a]pyrene (0.05% w/v in toluene) induced tumors in 46 of 50 mice,
      demonstrating the effectiveness of the test method. Salmonella typhimurium tester
      strain TA98 was used in the optimized Ames assay to evaluate mutagenic potential.
      Dimethylsulfoxide (DMSO) extractions of the substances were not mutagenic when
      tested up to toxic limits. Thus, under the conditions of these studies, neither
      the paving asphalt nor the vacuum residuum was carcinogenic or mutagenic.

PMID- 21878557
TI  - A metabonomic characterization of (+)-usnic acid-induced liver injury by gas
      chromatography-mass spectrometry-based metabolic profiling of the plasma and
      liver in rat.
AB  - Three doses of (+)-usnic acid (100, 200, and 240 mg/kg per d) were administered
      orally to Wistar rats for 8 days, and metabonomic characterization of (+)-usnic
      acid-induced liver injury based on gas chromatography-mass spectrometry metabolic
      profiles was evaluated. Serum biochemical analysis and histopathological
      examinations were simultaneously performed. The liver/body weight ratio was
      significantly increased in (+)-usnic acid-treated groups, whereas serum alanine
      aminotransferase and total bilirubin were significantly elevated. In liver
      sections of 200 and 240 mg/kg dosage groups, widespread hydropic degeneration of
      hepatocytes was observed. Clusters in partial least squares discriminant analysis
      score plots showed control and (+)-usnic acid-treated groups had an obvious
      separation. (+)-Usnic acid exposure can lead to disturbances in energy
      metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism,
      which may be attributable to (+)-usnic acid toxicological effects on the liver
      through oxidative stress. The significant changes in 22 metabolites in liver
      might be adopted as potential biomarkers.

PMID- 21878558
TI  - Complex N-acetylation of triethylenetetramine.
AB  - Triethylenetetramine (TETA) is an efficient copper chelator that has versatile
      clinical potential. We have recently shown that spermidine/spermine-N(1)
      acetyltransferase (SSAT1), the key polyamine catabolic enzyme, acetylates TETA in
      vitro. Here, we studied the metabolism of TETA in three different mouse lines:
      syngenic, SSAT1-overexpressing, and SSAT1-deficient (SSAT1-KO) mice. The mice
      were sacrificed at 1, 2, or 4 h after TETA injection (300 mg/kg i.p.). We found
      only N(1)-acetyltriethylenetetramine (N(1)AcTETA) and/or TETA in the liver,
      kidney, and plasma samples. As expected, SSAT1-overexpressing mice acetylated
      TETA at an accelerated rate compared with syngenic and SSAT1-KO mice. It is
      noteworthy that SSAT1-KO mice metabolized TETA as syngenic mice did, probably by
      thialysine acetyltransferase, which had a K(m) value of 2.5 +/- 0.3 mM and a
      k(cat) value of 1.3 s(-1) for TETA when tested in vitro with the human
      recombinant enzyme. Thus, the present results suggest that there are at least two
      N-acetylases potentially metabolizing TETA. However, their physiological
      significance for TETA acetylation requires further studies. Furthermore, we
      detected chemical intramolecular N-acetyl migration from the N(1) to N(3)
      position of N(1)AcTETA and N(1),N(8)-diacetyltriethylenetetramine in an acidified
      high-performance liquid chromatography sample matrix. The complex metabolism of
      TETA together with the intramolecular N-acetyl migration may explain the huge
      individual variations in the acetylation rate of TETA reported earlier.

PMID- 21878559
TI  - Variations in ATP-binding cassette transporter regulation during the progression
      of human nonalcoholic fatty liver disease.
AB  - Transporters located on the sinusoidal and canalicular membranes of hepatocytes
      regulate the efflux of drugs and metabolites into blood and bile, respectively.
      Changes in the expression or function of these transporters during liver disease
      may lead to a greater risk of adverse drug reactions. Nonalcoholic fatty liver
      disease (NAFLD) is a progressive condition encompassing the relatively benign
      steatosis and the more severe, inflammatory state of nonalcoholic steatohepatitis
      (NASH). Here, we present an analysis of the effect of NAFLD progression on the
      major ATP-binding cassette (ABC) efflux transport proteins ABCC1-6, ABCB1, and
      ABCG2. Human liver samples diagnosed as normal, steatotic, NASH (fatty), and NASH
      (not fatty) were analyzed. Increasing trends in mRNA expression of ABCC1, ABCC4
      5, ABCB1, and ABCG2 were found with NAFLD progression, whereas protein levels of
      all transporters exhibited increasing trends with disease progression.
      Immunohistochemical staining of ABCC3, ABCB1, and ABCG2 revealed no alterations
      in cellular localization during NAFLD progression. ABCC2 staining revealed an
      alternative mechanism of regulation in NASH in which the transporter appears to
      be internalized away from the canalicular membrane. This correlated with a
      preferential shift in the molecular mass of ABCC2 from 200 to 180 kDa in NASH,
      which has been shown to be associated with a loss of glycosylation and
      internalization of the protein. These data demonstrate increased expression of
      multiple efflux transporters as well as altered cellular localization of ABCC2 in
      NASH, which may have profound effects on the ability of patients with NASH to
      eliminate drugs in an appropriate manner.

PMID- 21878560
TI  - Long-term stability of clinical laboratory data: sodium as benchmark.

PMID- 21878561
TI  - SPINK1: a new therapeutic target in cancer?

PMID- 21878562
TI  - Horizontal gene transfer facilitated the evolution of plant parasitic mechanisms
      in the oomycetes.
AB  - Horizontal gene transfer (HGT) can radically alter the genomes of microorganisms,
      providing the capacity to adapt to new lifestyles, environments, and hosts.
      However, the extent of HGT between eukaryotes is unclear. Using whole-genome,
      gene-by-gene phylogenetic analysis we demonstrate an extensive pattern of cross
      kingdom HGT between fungi and oomycetes. Comparative genomics, including the de
      novo genome sequence of Hyphochytrium catenoides, a free-living sister of the
      oomycetes, shows that these transfers largely converge within the radiation of
      oomycetes that colonize plant tissues. The repertoire of HGTs includes a large
      number of putatively secreted proteins; for example, 7.6% of the secreted
      proteome of the sudden oak death parasite Phytophthora ramorum has been acquired
      from fungi by HGT. Transfers include gene products with the capacity to break
      down plant cell walls and acquire sugars, nucleic acids, nitrogen, and phosphate
      sources from the environment. Predicted HGTs also include proteins implicated in
      resisting plant defense mechanisms and effector proteins for attacking plant
      cells. These data are consistent with the hypothesis that some oomycetes became
      successful plant parasites by multiple acquisitions of genes from fungi.

PMID- 21878564
TI  - The neuronal K-Cl cotransporter KCC2 influences postsynaptic AMPA receptor
      content and lateral diffusion in dendritic spines.
AB  - The K-Cl cotransporter KCC2 plays an essential role in neuronal chloride
      homeostasis, and thereby influences the efficacy and polarity of GABA signaling.
      Although KCC2 is expressed throughout the somatodendritic membrane, it is
      remarkably enriched in dendritic spines, which host most glutamatergic synapses
      in cortical neurons. KCC2 has been shown to influence spine morphogenesis and
      functional maturation in developing neurons, but its function in mature dendritic
      spines remains unknown. Here, we report that suppressing KCC2 expression
      decreases the efficacy of excitatory synapses in mature hippocampal neurons. This
      effect correlates with a reduced postsynaptic aggregation of GluR1-containing
      AMPA receptors and is mimicked by a dominant negative mutant of KCC2 interaction
      with cytoskeleton but not by pharmacological suppression of KCC2 function. Single
      particle tracking experiments reveal that suppressing KCC2 increases lateral
      diffusion of the mobile fraction of AMPA receptor subunit GluR1 in spines but not
      in adjacent dendritic shafts. Increased diffusion was also observed for
      transmembrane but not membrane-anchored recombinant neuronal cell adhesion
      molecules. We suggest that KCC2, likely through interactions with the actin
      cytoskeleton, hinders transmembrane protein diffusion, and thereby contributes to
      their confinement within dendritic spines.

PMID- 21878565
TI  - Stereotyped fetal brain disorganization is induced by hypoxia and requires
      lysophosphatidic acid receptor 1 (LPA1) signaling.
AB  - Fetal hypoxia is a common risk factor that has been associated with a range of
      CNS disorders including epilepsy, schizophrenia, and autism. Cellular and
      molecular mechanisms through which hypoxia may damage the developing brain are
      incompletely understood but are likely to involve disruption of the laminar
      organization of the cerebral cortex. Lysophosphatidic acid (LPA) is a bioactive
      lipid capable of cortical influences via one or more of six cognate G protein
      coupled receptors, LPA(1-6), several of which are enriched in fetal neural
      progenitor cells (NPCs). Here we report that fetal hypoxia induces cortical
      disruption via increased LPA(1) signaling involving stereotyped effects on NPCs:
      N-cadherin disruption, displacement of mitotic NPCs, and impaired neuronal
      migration, as assessed both ex vivo and in vivo. Importantly, genetic removal or
      pharmacological inhibition of LPA(1) prevented the occurrence of these hypoxia
      induced phenomena. Hypoxia resulted in overactivation of LPA(1) through selective
      inhibition of G protein-coupled receptor kinase 2 expression and activation of
      downstream pathways including G(alphai) and Ras-related C3 botulinum toxin
      substrate 1. These data identify stereotyped and selective hypoxia-induced
      cerebral cortical disruption requiring LPA(1) signaling, inhibition of which can
      reduce or prevent disease-associated sequelae, and may take us closer to
      therapeutic treatment of fetal hypoxia-induced CNS disorders and possibly other
      forms of hypoxic injury.

PMID- 21878566
TI  - Mouse model of Timothy syndrome recapitulates triad of autistic traits.
AB  - Autism and autism spectrum disorder (ASD) typically arise from a mixture of
      environmental influences and multiple genetic alterations. In some rare cases,
      such as Timothy syndrome (TS), a specific mutation in a single gene can be
      sufficient to generate autism or ASD in most patients, potentially offering
      insights into the etiology of autism in general. Both variants of TS (the milder
      TS1 and the more severe TS2) arise from missense mutations in alternatively
      spliced exons that cause the same G406R replacement in the Ca(V)1.2 L-type
      calcium channel. We generated a TS2-like mouse but found that heterozygous (and
      homozygous) animals were not viable. However, heterozygous TS2 mice that were
      allowed to keep an inverted neomycin cassette (TS2-neo) survived through
      adulthood. We attribute the survival to lowering of expression of the G406R L
      type channel via transcriptional interference, blunting deleterious effects of
      mutant L-type channel overactivity, and addressed potential effects of altered
      gene dosage by studying Ca(V)1.2 knockout heterozygotes. Here we present a
      thorough behavioral phenotyping of the TS2-neo mouse, capitalizing on this unique
      opportunity to use the TS mutation to model ASD in mice. Along with normal
      general health, activity, and anxiety level, TS2-neo mice showed markedly
      restricted, repetitive, and perseverative behavior, altered social behavior,
      altered ultrasonic vocalization, and enhanced tone-cued and contextual memory
      following fear conditioning. Our results suggest that when TS mutant channels are
      expressed at levels low enough to avoid fatality, they are sufficient to cause
      multiple, distinct behavioral abnormalities, in line with the core aspects of
      ASD.

PMID- 21878567
TI  - Improved vascular organization enhances functional integration of engineered
      skeletal muscle grafts.
AB  - Severe traumatic events such as burns, and cancer therapy, often involve a
      significant loss of tissue, requiring surgical reconstruction by means of
      autologous muscle flaps. The scant availability of quality vascularized flaps and
      donor site morbidity often limit their use. Engineered vascularized grafts
      provide an alternative for this need. This work describes a first-time analysis,
      of the degree of in vitro vascularization and tissue organization, required to
      enhance the pace and efficacy of vascularized muscle graft integration in vivo.
      While one-day in vitro was sufficient for graft integration, a three-week
      culturing period, yielding semiorganized vessel structures and muscle fibers,
      significantly improved grafting efficacy. Implanted vessel networks were
      gradually replaced by host vessels, coupled with enhanced perfusion and capillary
      density. Upregulation of key graft angiogenic factors suggest its active role in
      promoting the angiogenic response. Transition from satellite cells to mature
      fibers was indicated by increased gene expression, increased capillary to fiber
      ratio, and similar morphology to normal muscle. We suggest a "relay" approach in
      which extended in vitro incubation, enabling the formation of a more structured
      vascular bed, allows for graft-host angiogenic collaboration that promotes
      anastomosis and vascular integration. The enhanced angiogenic response supports
      enhanced muscle regeneration, maturation, and integration.

PMID- 21878568
TI  - Lack of data to support a relationship between methane contamination of drinking
      water wells and hydraulic fracturing.

PMID- 21878569
TI  - Hydraulic fracturing not responsible for methane migration.

PMID- 21878571
TI  - Why do influenza virus subtypes die out? A hypothesis.
AB  - Novel pandemic influenza viruses enter the human population with some regularity
      and can cause disease that is severe and widespread. The emergence of novel
      viruses, historically, has often been coupled with the disappearance of existing
      seasonal virus strains. Here, we propose that the elimination of seasonal strains
      during virus pandemics is a process mediated, at the population level, by humoral
      immunity. Specifically, we suggest that infection with a novel virus strain, in
      people previously exposed to influenza viruses, can elicit a memory B cell
      response against conserved hemagglutinin stalk epitopes and/or neuraminidase
      epitopes. The anti-stalk and/or anti-neuraminidase antibodies then act to
      diminish the clinical severity of disease caused by novel influenza viruses and
      to eliminate seasonal virus strains.

PMID- 21878570
TI  - Linkage specificity and role of properdin in activation of the alternative
      complement pathway by fungal glycans.
AB  - Fungal cell walls are predominantly composed of glucans, mannans, and chitin.
      Recognition of these glycans by the innate immune system is a critical component
      of host defenses against the mycoses. Complement, an important arm of innate
      immunity, plays a significant role in fungal pathogenesis, especially the
      alternative pathway (AP). Here we determine that the glycan monosaccharide
      composition and glycosidic linkages affect AP activation and C3 deposition.
      Furthermore, properdin, a positive regulator of the AP, contributes to these
      functions. AP activation by glycan particles that varied in composition and
      linkage was measured by C3a generation in serum treated with 10 mM EGTA and 10 mM
      Mg(2+) (Mg-EGTA-treated serum) (AP specific; properdin functional) or Mg-EGTA
      treated serum that lacked functional properdin. Particles that contained either
      beta1->3 or beta1->6 glucans or both generated large and similar amounts of C3a
      when the AP was intact. Blocking properdin function resulted in 5- to 10-fold
      less C3a production by particulate beta1->3 glucans. However, particulate beta1
      >6 glucans generated C3a via the AP only in the presence of intact properdin.
      Interestingly, zymosan and glucan-mannan particles (GMP), which contain both beta
      glucans and mannans, also required properdin to generate C3a. The beta1->4
      glycans chitin and chitosan minimally activated C3 even when properdin was
      functional. Finally, properdin binding to glucan particles (GP) and zymosan in
      serum required active C3. Properdin colocalized with bound C3, suggesting that in
      the presence of serum, properdin bound indirectly to glycans through C3
      convertases. These findings provide a better understanding of how properdin
      facilitates AP activation by fungi through interaction with the cell wall
      components. IMPORTANCE: Invasive fungal infections have increased in incidence
      with the widespread use of immunosuppressive therapy and invasive procedures.
      Activation of the complement system contributes to innate immunity against fungi
      by generating chemoattractants that recruit white blood cells and by coating the
      pathogen with complement fragments that "mark" them for phagocytosis. The fungal
      cell wall activates complement in an antibody-independent manner through the
      alternative pathway (AP). Properdin is a positive regulator of the AP. This study
      elucidates how the specificity of cell wall glycan linkages affects AP activation
      and the role properdin plays in this process. Particulate beta1->3 glucans
      activated the AP even in the absence of properdin, while beta1->6 glucans
      required properdin for AP activation. In contrast, the beta1->4 glycans chitin
      and chitosan failed to activate the AP. These findings enhance our mechanistic
      understanding of how fungi activate complement and have implications for the use
      of glycans in biomedical applications.

PMID- 21878572
TI  - Apoptosis gene signature of Survivin and its splice variant expression in breast
      carcinoma.
AB  - Survivin, an anti-apoptotic protein, was described as strongly expressed in human
      cancers including breast cancer. However, little is known about the association
      between Survivin variants (Survivin-2B, Survivin-DeltaEx3, Survivin-3B, and
      Survivin-2alpha) and the other apoptotic-related genes. In this study, we
      analyzed the apoptosis gene signature of Survivin and its variant expression in
      breast cancer. Human Apoptosis Gene Arrays were used to screen genes that could
      be associated with Survivin variants. Expression of the five transcripts was
      measured by RT-PCR in 135 breast carcinomas and Cox survival analysis was
      analyzed according to the patient outcome. Significant associations between
      Survivin transcripts and apoptotic genes were found. Interestingly, Survivin-3B
      variant showed major inverse correlations with pro-apoptotic genes. In addition,
      in vitro results indicated that overexpression of Survivin-3B strongly inhibits 5
      fluorouracil/epirubicin/cyclophosphamide-induced apoptosis in breast tumor cell
      lines. In breast carcinomas, uni- and multivariate analysis showed patients with
      high level of Survivin-3B expression had a shorter overall (P=0.030 and P=0.042
      respectively), and disease-free (P=0.024 and P=0.009) survival. Our data suggest
      that Survivin-3B contributes to cell survival through the anti-apoptotic pathway
      and that its expression level could be an important factor in determining
      therapeutic strategies for breast carcinoma.

PMID- 21878573
TI  - Potential life-threatening events in schools involving rescue inhalers,
      epinephrine autoinjectors, and glucagon delivery devices: reports from school
      nurses.
AB  - The purpose of this research is to use the reports of school nurses to facilitate
      the understanding of how schools experience and manage asthmatic, anaphylactic,
      and diabetic emergencies by quantitative and qualitative analysis of online
      surveys. E-mails with a link to SurveyMonkey(r) were sent to all U.S. members of
      the National Association of School Nurses (13,695). Subjects were asked to
      describe their self-reported knowledge, opinions, practices, and experiences with
      such emergencies and the devices used to manage them. Regarding the frequency of
      emergencies in a given school year, the medians were 8 for asthma, 0 for
      anaphylaxis, and 10 for hypoglycemia. Twenty-two, five, and one subjects,
      respectively, reported that events like these resulted in deaths during their
      careers as school nurses. These diseases create substantial potential for
      emergencies in schools, and the schools represented by these nurses appear to be
      somewhat, but not ideally, equipped to handle such crises.

PMID- 21878574
TI  - Development and psychometric evaluation of a new instrument for measuring sleep
      length and television and computer habits of Swedish school-age children.
AB  - The aim was to develop a new instrument for measuring length of sleep as well as
      television and computer habits in school-age children. A questionnaire was
      constructed for use when children visit the school health care unit. Three
      aspects of the validity of the questionnaire were examined: its face validity,
      content validity, and construct validity. Test-retest reliability was assessed by
      giving the questionnaire twice, 2 weeks apart, to the respondents. The
      questionnaire was assessed as being reasonably valid, the test-retest results (n
      = 138) showing 90.4% of the estimates regarding bedtime on weeknights on the two
      survey occasions to lie within +/- 30 min of each other, the test-retest
      agreement also being rather close (kappa > .600) regarding both sleep and media
      habits. The instrument can be a valuable tool in a clinical setting, both for
      measuring sleep habits in a class and for discussing sleep with individual school
      children and their families.

PMID- 21878575
TI  - A School-Based Health Center-University Nursing Partnership: How We Filled in the
      GAPS.
AB  - Young adolescents, age 10-15 years, have increasing psychosocial and biomedical
      health care needs, yet are some of the lowest users of conventional health
      services. In eastern North Carolina, school-based health centers (SBHCs) provide
      primary health care to thousands of school-age children in the most rural,
      medically underserved areas. SBHCs receive reimbursement from local, state, and
      private funding sources and their viability depends on the demonstration of
      outcomes. Using the Guidelines for Adolescent Preventive Services (GAPS)
      assessment tool, an SBHC-university nursing partnership evaluated the use of
      preventive health services by fifth and sixth grade students (n = 690). Findings
      suggest that the vast majority of early adolescents needed a referral for a
      physical exam, nutrition, mental health, or health education services. This
      article describes key components for a successful SBHC-university nursing
      partnership that can evaluate and improve existing school health programs.

PMID- 21878577
TI  - The linkage of life course, migration, health, and aging: health in adults and
      elderly Mexican migrants.
AB  - Migration is a phenomenon that impacts individuals throughout the life course.
      Particularly, Mexican elderly migrants show evidence of lifetime accumulations of
      the effects of migration on health conditions. OBJECTIVES: Examine how the
      relationship between historical time and individual time explains different
      factors impacting the health of Mexican adult and elderly migrants in Mexico and
      the United States. METHOD: Data from in-depth interviews with Mexican migrants
      living in selected locations in Mexico and the United States were used to
      illustrate the links between life course conditions, aging, migration, and health
      outcomes. RESULTS AND DISCUSSION: According to this theoretical perspective and
      the data, historical time, age at migration, and the conditions under which the
      migration trajectory developed, show different impacts on the health and quality
      of life of the elderly, as revealed through analysis of labor experience, disease
      and accidents, medical service, health treatment, transnational networks, and
      family formation.

PMID- 21878578
TI  - Randomized 5-treatment crossover study to assess the effects of external heat on
      serum fentanyl concentrations during treatment with transdermal fentanyl systems.
AB  - This randomized, open-label, 5-treatment, 5-sequence crossover study was designed
      to evaluate the effects of a heating pad on serum fentanyl concentrations with
      reservoir and matrix transdermal fentanyl systems. Subjects were randomized to 1
      of 5 treatment sequences, receiving 5 fentanyl treatments (1 per period) for 36
      hours: 25 ug/h reservoir without heat, 25 ug/h reservoir with heat, 25 ug/h
      matrix without heat, 25 ug/h matrix with heat, and a 50 ug/h reservoir without
      heat. The 25 ug/h systems with heat had a heating pad applied from 0 to 10 and 26
      to 36 hours post application. Washout periods between treatments were 5 to 14
      days. Naltrexone was given to block the opioid effects of fentanyl. Study results
      indicate that external heat had a similar effect on both matrix and reservoir
      systems, with heat applied during the first 10 hours of treatment increasing
      fentanyl exposure by approximately 61% to 81% at 10 hours (observed serum
      concentration at 10 hours) and overall exposure (area under the curve from 0 to
      10 hours) by approximately 120% to 184%, but had minimal effect from 26 to 36
      hours. The increased exposure observed with heat in both 25 ug/h systems, between
      0 and 10 hours, was higher than that obtained with the 50 ug/h reservoir system
      applied without heat.

PMID- 21878579
TI  - Dosing celecoxib in pediatric patients with juvenile rheumatoid arthritis.
AB  - The objective was to derive dosing recommendations for the use of celecoxib in
      patients with juvenile rheumatoid arthritis (JRA) using pharmacokinetic (PK) and
      exposure-response data. PK and efficacy data from a randomized, double-blind, 12
      week study of celecoxib dosed at 3 and 6 mg/kg twice a day (bid) as an
      investigational suspension formulation in 152 JRA patients aged 2 to 17 years, PK
      data from 36 adult RA patients, and relative bioavailability data in healthy
      adults comparing suspension or capsule sprinkles with the commercial capsule were
      analyzed. Typical oral clearance (L/h) values were 40% and 24% lower in patients
      weighing 10 and 25 kg, respectively, compared with a 70-kg patient. Longitudinal,
      logistic pharmacodynamic models incorporating linear effects of dose/area under
      the plasma concentration-time curve (AUC) over 0 to 12 hours (AUC(0-12))
      suggested that the percentage of responders increased with celecoxib exposure.
      Systemic exposures (AUC) were similar for the suspension, capsule sprinkles, and
      intact capsule. Administration of a 50-mg bid capsule (or sprinkles) for patients
      weighing 10 to 25 kg and 100 mg bid for patients >25 kg was predicted to yield
      similar exposures and response rates as those observed in the JRA trial. Doses
      and dosage forms not studied in the JRA trial were approved based on the results
      of this analysis.

PMID- 21878580
TI  - Minimal impact of excess iodate intake on thyroid hormones and selenium status in
      older New Zealanders.
AB  - OBJECTIVE: Iodine deficiency has re-emerged in New Zealand, while selenium status
      has improved. The aim of this study was to investigate the effects of excess
      iodine intake as iodate on thyroid and selenium status. METHODS: In a randomized
      controlled trial on older people (mean+/-s.d. 73+/-4.8 years; n=143), two groups
      received >50  mg iodine as iodate/day for 8 weeks because of supplement
      formulation error, either with 100  MUg selenium (Se+highI) or without selenium
      (highI). Four other groups received 80  MUg iodine as iodate/day with selenium
      (Se+lowI) or without selenium (lowI), selenium alone (Se+), or placebo. Thyroid
      hormones, selenium status, and median urinary iodine concentration (MUIC) were
      compared at weeks 0, 8, and 4 weeks post-supplementation. RESULTS: MUIC increased
      nine- and six-fold in Se+highI and highI groups, decreasing to baseline by week
      12. Plasma selenium increased in selenium-supplemented groups (P<0.001). The
      level of increase in whole blood glutathione peroxidase (WBGPx) in the Se+highI
      group was smaller than Se+ (P=0.020) and Se+lowI (P=0.007) groups. The decrease
      in WBGPX in the highI group was greater than other non-selenium-supplemented
      groups, but differences were not significant. Ten of 43 participants exposed to
      excess iodate showed elevated TSH (hypothyroidism) at week 8. In all but two, TSH
      had returned to normal by week 12. In three participants, TSH decreased to <0.10 
      mIU/l (hyperthyroidism) at week 8, remaining low at week 12. CONCLUSIONS: Excess
      iodate induced hypothyroidism in some participants and hyperthyroidism in others.
      Most abnormalities disappeared after 4 weeks. Excess iodate reduced WBGPx
      activity and resulted in smaller increases in WBGPx after selenium
      supplementation.

PMID- 21878582
TI  - Knowledge and practice of Jordanian emergency nurses caring for patients with
      drug-seeking behaviors.
AB  - The purpose of this study was to investigate the meaning and knowledge level and
      practices of emergency nurses in Jordan in relation to drug-seeking behaviors in
      the emergency units in Jordan. A descriptive correlation design was used. Data
      were collected using self-report questionnaires from 305 emergency nurses,
      employed in different emergency departments (EDs) in Jordan. The results of this
      study revealed that the ED nurses had a moderate level of ability to describe
      patients with drug-seeking behaviors, had moderate agreement on the behaviors
      that may suggest drug seeking, and a moderate level of knowledge related to drug
      seeking behaviors. The analyses also showed that the ED nurses had negative
      attitudes toward drug-seeking behaviors, and lacked the ability to manage drug
      seeking behaviors, when identified. Nurses in the EDs who completed the
      questionnaires identified a need for more drug seeking-behavior knowledge and
      skills to assess and manage this condition more effectively.

PMID- 21878581
TI  - Determinants of excessive daytime sleepiness and fatigue in adults with heart
      failure.
AB  - Little is known about excessive daytime sleepiness (EDS) in heart failure (HF).
      The aim of this cross-sectional descriptive study was to describe the prevalence
      of EDS and factors associated with it in HF. A secondary purpose was to explore
      the correlates of fatigue. We enrolled a consecutive sample of 280 adults with a
      confirmed diagnosis of chronic HF from three outpatient settings in the
      northeastern United States. Patients with major depressive illness were excluded.
      Clinical, sociodemographic, behavioral, and perceptual factors were explored as
      possible correlates of EDS. Using an Epworth Sleepiness Scale score > 10, the
      prevalence of EDS was 23.6%. Significant determinants of EDS were worse sleep
      quality (p = .048), worse functional class (p = .004), not taking a diuretic (p =
      .005), and lack of physical activity (p = .04). Only sleep quality was associated
      with fatigue (p < .001). Sleep-disordered breathing was not significantly
      associated with EDS or with fatigue. These factors may be amenable to
      intervention.

PMID- 21878583
TI  - Response to homeless childbearing women's health care learning needs.
AB  - The study findings showed that homeless childbearing women are at greatest risk
      for cancer, violence, poor nutrition, sexually transmitted infections, unplanned
      pregnancy, and adverse pregnancy outcomes. Collaborating with personnel at a
      women's shelter, the authors studied homeless childbearing women's knowledge,
      attitudes, and beliefs about general health promotion, healthy pregnancy
      promotion, and preterm labor prevention. Guided by the Integrative Model of
      Behavioral Prediction and Change, 45 homeless women participated in focus groups.
      They were 28.7 years old (range 18-44 years), and approximately 87% of these
      women had custody of their children. Three themes identified included things you
      do to stay healthy during pregnancy, where you learned about staying healthy, and
      women's knowledge about preterm labor and general health promotion. These
      findings informed an 8-week educational session (1 hr/week). During the past
      year, four 8-week sessions were conducted with attendance between 8 and 14
      participants. Each week a different health topic was discussed incorporating the
      associated unique challenges of homelessness.

PMID- 21878584
TI  - A 30-year-old male with a 4-week history of shortness of breath, productive
      cough, and weight loss.

PMID- 21878585
TI  - Enteroviral meningitis does not exclude concurrent bacterial meningitis.

PMID- 21878586
TI  - Evaluation of real-time reverse transcriptase PCR assays for detection of
      pandemic influenza A/H1N1 2009 virus.

PMID- 21878587
TI  - Revision of interpretation criteria of the INNO-LiPA HBV genotyping assay.

PMID- 21878589
TI  - Long-term safety of radiotherapy and breast cancer laterality in older survivors.
AB  - BACKGROUND: Although adjuvant radiotherapy (RT) following surgery for breast
      cancer improves overall survival, controversy exists about its long-term adverse
      impact on cardiovascular health in older survivors. AIM: To determine whether
      incident cardiovascular disease (CVD) is associated with RT and whether tumor
      laterality modifies this association. METHODS: Women aged 65+ years diagnosed
      with stage I and II breast cancer between 1990 and 1994 were identified from
      three health plans. Women were followed through CVD outcomes, health plan
      disenrollment, death, or study end (December 31, 2004). The main independent
      variable was RT use. Adjusted HRs and 95% CIs were estimated using Cox
      proportional hazards models with time-dependent tamoxifen and RT use status. We
      adjusted for age, race, stage, estrogen receptor/progesterone receptor,
      hypertension, and diabetes. RESULTS: In the full cohort (N = 806), RT was not
      associated with greater risk of CVD (maximum follow-up was 14 years). However,
      within the RT-exposed group (N = 340), women treated for left-side breast cancer
      had a significant increased risk of CVD outcomes (HR = 1.53, 95% CI: 1.06-2.21)
      compared with women with right-sided tumors. CONCLUSION: Laterality is critical
      to understanding the effect of RT on CVD. Studies of more contemporary cohorts of
      women treated with RT should incorporate this variable to determine whether the
      risk persists with refinements in the dosing and delivery of RT. IMPACT: As some
      irradiation to the heart is unavoidable even with refined modern RT techniques,
      continued effort is required to minimize such exposures, especially in older
      women with left-sided tumors.

PMID- 21878590
TI  - Exploring the presence of Matthew effects in learning disabilities.

PMID- 21878591
TI  - Assessing the value of the diabetes educator.
AB  - PURPOSE: The purpose of this study was to evaluate the effectiveness of diabetes
      self-management education or training provided by diabetes educators in reducing
      complications and improving quality of life. METHODS: Commercial and Medicare
      payer-derived claims data were used to assess the relationship between DSME/T and
      cost. Unlike the prior study that examined diabetes education provided by all
      professionals, the current study focused on the value of interventions performed
      as part of formal accredited/recognized diabetes education programs provided by
      diabetes educators only. Specifically, the current study focused on diabetes
      education delivered in diabetes self-management training programs based on 2
      codes (G0108 and G0109). RESULTS: Results of the study provide insights into the
      differences in trends between participants and nonparticipants in DSMT. People
      with diabetes who had DSMT encounters provided by diabetes educators in
      accredited/recognized programs are likely to show lower cost patterns when
      compared with a control group of people with diabetes without DSMT encounters.
      People with diabetes who have multiple episodes of DSMT are more likely to
      receive care in accordance with recommended guidelines and to comply with
      diabetes-related prescription regimens, resulting in lower costs and utilization
      trends. Conclusions and Policy Implications The collaboration between diabetes
      educators and patients continues to demonstrate positive clinical quality
      outcomes and cost savings. This analysis shows that repeated DSMT encounters over
      time result in a dose-response effect on positive outcomes.

PMID- 21878592
TI  - Clinical, dermatoscopic, and microscopic findings of infestation with Sarcoptes
      scabiei var hominis.

PMID- 21878593
TI  - Clinical outcomes associated with robotic repair of the mitral valve.

PMID- 21878594
TI  - Electronic communication and medical research: beyond the record.

PMID- 21878595
TI  - Spontaneous coronary artery dissection: a disease-specific, social networking
      community-initiated study.
AB  - OBJECTIVE: To develop and assess the feasibility of a novel method for
      identification, recruitment, and retrospective and prospective evaluation of
      patients with rare conditions. PATIENTS AND METHODS: This pilot study is a novel
      example of "patient-initiated research." After being approached by several
      members of an international disease-specific support group on a social networking
      site, we used it to identify patients who had been diagnosed as having at least 1
      episode of spontaneous coronary artery dissection and recruited them to
      participate in a clinical investigation of their condition. Medical records were
      collected and reviewed, the original diagnosis was independently confirmed by
      review of imaging studies, and health status (both interval and current) was
      assessed via specially designed questionnaires and validated assessment tools.
      RESULTS: Recruitment of all 12 participants was complete within 1 week of
      institutional review board approval (March 18, 2010). Data collection was
      completed November 18, 2010. All participants completed the study questionnaires
      and provided the required medical records and coronary angiograms and ancillary
      imaging data. CONCLUSION: This study involving patients with spontaneous coronary
      artery dissection demonstrates the feasibility of and is a successful model for
      developing a "virtual" multicenter disease registry through disease-specific
      social media networks to better characterize an uncommon condition. This study is
      a prime example of patient-initiated research that could be used by other health
      care professionals and institutions.

PMID- 21878596
TI  - Posterior reversible encephalopathy syndrome and eclampsia: pressing the case for
      more aggressive blood pressure control.
AB  - OBJECTIVE: To assess the prevalence, clinical presentations, and neuroimaging
      abnormalities in a series of patients treated for eclampsia at Mayo Clinic in
      Rochester, MN. PATIENTS AND METHODS: We reviewed the records of all pregnant
      patients diagnosed as having eclampsia at Mayo Clinic in Rochester, MN, between
      January 1, 2001, and December 31, 2008. All patients who underwent neuroimaging
      were identified, and all studies were reviewed by an independent
      neuroradiologist. Comparisons were made between groups who did and did not
      undergo imaging to identify differentiating clinical or laboratory variables.
      RESULTS: Thirteen cases of eclampsia were found, with neuroimaging studies
      available for 7: magnetic resonance imaging (n=6) and computed tomography (n=1).
      All 7 patients developed eclamptic seizures, and 2 of 7 patients had severe
      hypertension, with recorded systolic blood pressures exceeding 180 mm Hg.
      Neuroimaging showed characteristic changes of posterior reversible encephalopathy
      syndrome (PRES) in all patients. Follow-up imaging showed resolution in 2 of 3
      patients; 1 patient had residual neuroimaging abnormalities. CONCLUSION: Our
      results suggest that the clinical syndrome of eclampsia is associated with an
      anatomical substrate that is recognizable by neuroimaging as PRES. The levels of
      blood pressure elevation are lower than those reported in cases of PRES because
      of hypertensive encephalopathy. Further studies are needed to determine whether
      more aggressive blood pressure control and early neuroimaging may have a role in
      the management of these patients.

PMID- 21878597
TI  - Body composition and coronary heart disease mortality--an obesity or a lean
      paradox?
AB  - OBJECTIVE: To determine the combined effects of body mass index (BMI) and body
      fat (BF) on prognosis in coronary heart disease (CHD) to better understand the
      obesity paradox. PATIENTS AND METHODS: We studied 581 patients with CHD between
      January 1, 2000, and July 31, 2005, who were divided into low (<25) and high BMI
      (>=25), as well as low (<=25% men and <=35% women) and high BF (>25% in men and
      >35% in women). Four groups were analyzed by total mortality during the 3-year
      follow-up by National Death Index: low BF/low BMI (n=119), high BF/low BMI
      (n=26), low BF/high BMI (n=125), and high BF/high BMI (n=311). RESULTS: During
      the 3-year follow-up, mortality was highest in the low BF/low BMI group (11%),
      which was significantly (P<.001) higher than that in the other 3 groups (3.9%,
      3.2%, and 2.6%, respectively); using the high BF/high BMI group as a reference,
      the low BF/low BMI group had a 4.24-fold increase in mortality (confidence
      interval [CI], 1.76-10.23; P=.001). In multivariate logistic regression for
      mortality, when entered individually, both high BMI (odds ratio [OR], 0.79; CI,
      0.69-0.90) and high BF (OR, 0.89; CI, 0.82-0.95) as continuous variables were
      independent predictors of better survival, whereas low BMI (OR, 3.60; CI, 1.37
      9.47) and low BF (OR, 3.52; CI, 1.34-9.23) as categorical variables were
      independent predictors of higher mortality. CONCLUSION: Although both low BF and
      low BMI are independent predictors of mortality in patients with CHD, only
      patients with combined low BF/low BMI appear to be at particularly high risk of
      mortality during follow-up. Studies are needed to determine optimal body
      composition in the secondary prevention of CHD.

PMID- 21878598
TI  - Patients' perspective on full disclosure and informed consent regarding
      postoperative visual loss associated with spinal surgery in the prone position.
AB  - OBJECTIVE: To determine patients' opinions regarding the person, method, and
      timing for disclosure of postoperative visual loss (POVL) associated with high
      risk surgery. PATIENTS AND METHODS: On the basis of findings of a pilot study
      involving 219 patients at Mayo Clinic in Florida, we hypothesized that at least
      80% of patients would prefer disclosure of POVL by the surgeon, during a face-to
      face discussion, before the day of scheduled surgery. To test the hypothesis, we
      sent a questionnaire to 437 patients who underwent prolonged prone spinal
      surgical procedures at Mayo Clinic in Rochester, MN, or Mayo Clinic in Arizona
      from December 1, 2008, to December 31, 2009. RESULTS: Among the 184 respondents,
      158 patients gave responses supporting the hypothesis vs 26 with at least 1
      response not supporting it, for an observed incidence of 86%. The 2-sided 95%
      confidence interval is 80% to 91%. CONCLUSION: At least 80% of patients prefer
      full disclosure of the risk of POVL, by the surgeon, during a face-to-face
      discussion before the day of scheduled surgery. This finding supports development
      of a national patient-driven guideline for disclosing the risk of POVL before
      prone spinal surgery.

PMID- 21878599
TI  - MMR vaccine and autism: vaccine nihilism and postmodern science.

PMID- 21878600
TI  - Physical exercise as a preventive or disease-modifying treatment of dementia and
      brain aging.
AB  - A rapidly growing literature strongly suggests that exercise, specifically
      aerobic exercise, may attenuate cognitive impairment and reduce dementia risk. We
      used PubMed (keywords exercise and cognition) and manuscript bibliographies to
      examine the published evidence of a cognitive neuroprotective effect of exercise.
      Meta-analyses of prospective studies documented a significantly reduced risk of
      dementia associated with midlife exercise; similarly, midlife exercise
      significantly reduced later risks of mild cognitive impairment in several
      studies. Among patients with dementia or mild cognitive impairment, randomized
      controlled trials (RCTs) documented better cognitive scores after 6 to 12 months
      of exercise compared with sedentary controls. Meta-analyses of RCTs of aerobic
      exercise in healthy adults were also associated with significantly improved
      cognitive scores. One year of aerobic exercise in a large RCT of seniors was
      associated with significantly larger hippocampal volumes and better spatial
      memory; other RCTs in seniors documented attenuation of age-related gray matter
      volume loss with aerobic exercise. Cross-sectional studies similarly reported
      significantly larger hippocampal or gray matter volumes among physically fit
      seniors compared with unfit seniors. Brain cognitive networks studied with
      functional magnetic resonance imaging display improved connectivity after 6 to 12
      months of exercise. Animal studies indicate that exercise facilitates
      neuroplasticity via a variety of biomechanisms, with improved learning outcomes.
      Induction of brain neurotrophic factors by exercise has been confirmed in
      multiple animal studies, with indirect evidence for this process in humans.
      Besides a brain neuroprotective effect, physical exercise may also attenuate
      cognitive decline via mitigation of cerebrovascular risk, including the
      contribution of small vessel disease to dementia. Exercise should not be
      overlooked as an important therapeutic strategy.

PMID- 21878601
TI  - Perioperative cognitive decline in the aging population.
AB  - Elderly patients who have an acute illness or who undergo surgery often
      experience cognitive decline. The pathophysiologic mechanisms that cause
      neurodegeneration resulting in cognitive decline, including protein deposition
      and neuroinflammation, also play a role in animal models of surgery-induced
      cognitive decline. With the aging of the population, surgical candidates of
      advanced age with underlying neurodegeneration are encountered more often,
      raising concerns that, in patients with this combination, cognitive function will
      precipitously decline postoperatively. This special article is based on a
      symposium that the University of California, San Francisco, convened to explore
      the contributions of surgery and anesthesia to the development of cognitive
      decline in the aged patient. A road map to further elucidate the mechanisms,
      diagnosis, risk factors, mitigation, and treatment of postoperative cognitive
      decline in the elderly is provided.

PMID- 21878602
TI  - The role of the primary care physician in helping adolescent and adult patients
      improve asthma control.
AB  - Many adolescents and adults with asthma continue to have poorly controlled
      disease, often attributable to poor adherence to asthma therapy. Failure to
      adhere to recommended treatment may result from a desire to avoid regular
      reliance on medications, inappropriate high tolerance of asthma symptoms, failure
      to perceive the chronic nature of asthma, and poor inhaler technique. Primary
      care physicians need to find opportunities and methods to address these and other
      issues related to poor asthma control. Few adolescents or adults with asthma
      currently have asthma "checkup" visits, usually seeking medical care only with an
      exacerbation. Therefore, nonrespiratory-related office visits represent an
      important opportunity to assess baseline asthma control and the factors that most
      commonly lead to poor control. Tools such as the Asthma Control Test, the Asthma
      Therapy Assessment Questionnaire, the Asthma Control Questionnaire, and the
      Asthma APGAR provide standardized, patient-friendly ways to capture necessary
      asthma information. For uncontrolled asthma, physicians can refer to the stepwise
      approach in the 2007 National Asthma Education and Prevention Program guidelines
      to adjust medication use, but they must consider step-up decisions in the context
      of quality of the patient's inhaler technique, adherence, and ability to
      recognize and avoid or eliminate triggers. For this review, a literature search
      of PubMed from 2000 through August 31, 2010, was performed using the following
      terms (or a combination of these terms): asthma, asthma control, primary care,
      NAEPP guidelines, assessment, uncontrolled asthma, burden, impact, assessment
      tools, triggers, pharmacotherapy, safety. Studies were limited to human studies
      published in English. Articles were also identified by a manual search of
      bibliographies from retrieved articles and from article archives of the author.

PMID- 21878603
TI  - The science of fibromyalgia.
AB  - Fibromyalgia (FM) is a common chronic widespread pain disorder. Our understanding
      of FM has increased substantially in recent years with extensive research
      suggesting a neurogenic origin for the most prominent symptom of FM, chronic
      widespread pain. Neurochemical imbalances in the central nervous system are
      associated with central amplification of pain perception characterized by
      allodynia (a heightened sensitivity to stimuli that are not normally painful) and
      hyperalgesia (an increased response to painful stimuli). Despite this increased
      awareness and understanding, FM remains undiagnosed in an estimated 75% of people
      with the disorder. Clinicians could more effectively diagnose and manage FM if
      they better understood its underlying mechanisms. Fibromyalgia is a disorder of
      pain processing. Evidence suggests that both the ascending and descending pain
      pathways operate abnormally, resulting in central amplification of pain signals,
      analogous to the "volume control setting" being turned up too high. Patients with
      FM also exhibit changes in the levels of neurotransmitters that cause augmented
      central nervous system pain processing; levels of several neurotransmitters that
      facilitate pain transmission are elevated in the cerebrospinal fluid and brain,
      and levels of several neurotransmitters known to inhibit pain transmission are
      decreased. Pharmacological agents that act centrally in ascending and/or
      descending pain processing pathways, such as medications with approved
      indications for FM, are effective in many patients with FM as well as other
      conditions involving central pain amplification. Research is ongoing to determine
      the role of analogous central nervous system factors in the other cardinal
      symptoms of FM, such as fatigue, nonrestorative sleep, and cognitive dysfunction.

PMID- 21878604
TI  - 65-year-old woman with shortness of breath and dark urine.

PMID- 21878605
TI  - Antiretroviral therapy and adverse skeletal effects.

PMID- 21878606
TI  - Premature discard of proton pump inhibitors: possible osteoporosis vs enhanced
      gastrointestinal bleed, adenocarcinoma efficacy.

PMID- 21878607
TI  - Taking stock of self-control: a meta-analysis of how trait self-control relates
      to a wide range of behaviors.
AB  - Given assertions of the theoretical, empirical, and practical importance of self
      control, this meta-analytic study sought to review evidence concerning the
      relationship between dispositional self-control and behavior. The authors provide
      a brief overview over prominent theories of self-control, identifying implicit
      assumptions surrounding the effects of self-control that warrant empirical
      testing. They report the results of a meta-analysis of 102 studies (total N =
      32,648) investigating the behavioral effects of self-control using the Self
      Control Scale, the Barratt Impulsiveness Scale, and the Low Self-Control Scale. A
      small to medium positive effect of self-control on behavior was found for the
      three scales. Only the Self-Control Scale allowed for a fine-grained analysis of
      conceptual moderators of the self-control behavior relation. Specifically, self
      control (measured by the Self-Control Scale) related similarly to the performance
      of desired behaviors and the inhibition of undesired behaviors, but its effects
      varied dramatically across life domains (e.g., achievement, adjustment). In
      addition, the associations between self-control and behavior were significantly
      stronger for automatic (as compared to controlled) behavior and for imagined (as
      compared to actual) behavior.

PMID- 21878608
TI  - Perception and motivation in face recognition: a critical review of theories of
      the Cross-Race Effect.
AB  - Although humans possess well-developed face processing expertise, face processing
      is nevertheless subject to a variety of biases. Perhaps the best known of these
      biases is the Cross-Race Effect--the tendency to have more accurate recognition
      for same-race than cross-race faces. The current work reviews the evidence for
      and provides a critical review of theories of the Cross-Race Effect, including
      perceptual expertise and social cognitive accounts of the bias. The authors
      conclude that recent hybrid models of the Cross-Race Effect, which combine
      elements of both perceptual expertise and social cognitive frameworks, provide an
      opportunity for theoretical synthesis and advancement not afforded by independent
      expertise or social cognitive models. Finally, the authors suggest future
      research directions intended to further develop a comprehensive and integrative
      understanding of biases in face recognition.

PMID- 21878609
TI  - Mycoplasma pneumoniae infection presenting as bullous papular purpuric gloves and
      socks syndrome: novel association and review of the literature.
AB  - Papular purpuric gloves and socks syndrome (PPGSS) is a self-limited, often
      febrile illness with symmetric edema and erythema of the hands and feet; papular,
      petechial, and purpuric acral dermatosis; and mucosal lesions in children and
      young adults. Most of the cases of PPGSS have been reported to be caused by
      parvovirus B19 and other viruses. This study describes a case resulting from
      Mycoplasma pneumoniae infection in an adolescent male and reviews the literature.

PMID- 21878610
TI  - Multiple tissue transcriptomic responses to Piscirickettsia salmonis in Atlantic
      salmon (Salmo salar).
AB  - The bacterium Piscirickettsia salmonis is the etiological agent of salmonid
      rickettsial septicemia (SRS), a severe disease that causes major economic losses
      to the Atlantic salmon aquaculture industry every year. Little is known about the
      infective strategy of P. salmonis, which is able to infect, survive within, and
      replicate inside salmonid macrophages as an intracellular parasite. Similarly
      there is little knowledge concerning the fish host's response to invasion by this
      pathogen. We have examined the transcriptional response of postsmolt Atlantic
      salmon (Salmo salar) to P. salmonis at 48 h following infection in three tissues,
      liver, head kidney, and muscle, using an Atlantic salmon oligonucleotide
      microarray (Salar_2, Agilent 4x44K). The infection led to a large alteration of
      transcriptional activity in all the tissues studied. In infected salmon 886, 207,
      and 153 transcripts were differentially expressed in liver, head kidney, and
      muscle, respectively. Assessment of enrichment for particular biological pathways
      by gene ontology analysis showed an upregulation of genes involved in oxidative
      and inflammatory responses in infected fish, indicative of the activation of the
      innate immune response. The downregulation of genes involved in the adaptive
      immune response, G protein signaling pathway, and apoptotic process in infected
      fish may be reflective of mechanisms used by P. salmonis to survive, replicate,
      and escape host defenses. There was also evidence of differential responses
      between studied tissues, with protein metabolism being decreased in muscle of
      infected fish and with a concomitant increase being shown in liver.

PMID- 21878611
TI  - Homogenous protein programming in the mammalian left and right ventricle free
      walls.
AB  - Despite identical cardiac outputs, the right (RV) and left ventricle (LV) have
      very different embryological origins and resting workload. These differences
      suggest that the ventricles have different protein programming with regard to
      energy metabolism and contractile elements. The objective of this study was to
      determine the relative RV and LV protein expression levels, with an emphasis on
      energy metabolism. The RV and LV protein contents of the rabbit and porcine heart
      were determined with quantitative gel electrophoresis (2D-DIGE), mass
      spectrometry, and optical spectroscopy techniques. Surprisingly, the expression
      levels for more than 600 RV and LV proteins detected were similar. This included
      proteins many different compartments and metabolic pathways. In addition, no
      isoelectric shifts were detected in 2D-DIGE consistent with no differential
      posttranslational modifications in these proteins. Analysis of the RV and LV
      metabolic response to work revealed that the metabolic rate increases much faster
      with workload in the RV compared with LV. This implies that the generally lower
      metabolic stress of the RV actually approaches LV metabolic stress at maximum
      workloads. Thus, identical levels of energy conversion and mechanical elements in
      the RV and LV may be driven by the performance requirements at maximum workloads.
      In summary, the ventricles of the heart manage the differences in overall
      workload by modifying the amounts of cytosol, not its composition. The constant
      myocyte composition in the LV and RV implies that the ratio of energy metabolism
      and contractile elements may be optimal for the sustained cardiac contractile
      activity in the mammalian heart.

PMID- 21878612
TI  - Profiling target genes of FGF18 in the postnatal mouse lung: possible relevance
      for alveolar development.
AB  - Better understanding alveolarization mechanisms could help improve prevention and
      treatment of diseases characterized by reduced alveolar number. Although
      signaling through fibroblast growth factor (FGF) receptors is essential for
      alveolarization, involved ligands are unidentified. FGF18, the expression of
      which peaks coincidentally with alveolar septation, is likely to be involved.
      Herein, a mouse model with inducible, lung-targeted FGF18 transgene was used to
      advance the onset of FGF18 expression peak, and genome-wide expression changes
      were determined by comparison with littermate controls. Quantitative RT-PCR was
      used to confirm expression changes of selected up- and downregulated genes and to
      determine their expression profiles in the course of lung postnatal development.
      This allowed identifying so-far unknown target genes of the factor, among which a
      number are known to be involved in alveolarization. The major target was
      adrenomedullin, a promoter of lung angiogenesis and alveolar development, whose
      transcript was increased 6.9-fold. Other genes involved in angiogenesis presented
      marked expression increases, including Wnt2 and cullin2. Although it appeared to
      favor cell migration notably through enhanced expression of Snai1/2, FGF18 also
      induced various changes consistent with prevention of epithelial-mesenchymal
      transition. Together with antifibrotic effects driven by induction of E
      prostanoid receptor 2 and repression of numerous myofibroblast markers, this
      could prevent alveolar septation-driving mechanisms from becoming excessive and
      deleterious. Last, FGF18 up- or downregulated genes of extracellular matrix
      components and epithelial cell markers previously shown to be up- or
      downregulated during alveolarization. These findings therefore argue for an
      involvement of FGF18 in the control of various developmental events during the
      alveolar stage.

PMID- 21878613
TI  - Source expertise and persuasion: the effects of perceived opposition or support
      on message scrutiny.
AB  - Compared to nonexperts, expert sources have been considered to elicit more
      processing of persuasive messages because of expectations that the information is
      likely to be valid or accurate. However, depending on the position of an
      advocacy, source expertise could activate other motives that may produce a very
      different relation from that found in past research. When messages are
      counterattitudinal (disagreeable), experts should motivate greater processing
      than nonexpert sources because of expectations that they will likely provide
      robust opposition to one's existing views. In contrast, when advocacies are
      proattitudinal (agreeable), nonexpert rather than expert sources should elicit
      more scrutiny because of perceptions that they will likely provide inadequate
      support to recipients' current views. Two studies offer evidence consistent with
      these predictions. Manipulations of source expertise created different
      expectations regarding the strength of opposition or support, and these
      perceptions accounted for effects of source expertise on the amount of message
      scrutiny.

PMID- 21878614
TI  - Arteriovenous fistulas for hemodialysis: application of high-frequency US to
      assess vein wall morphology for cannulation readiness.
AB  - PURPOSE: To determine whether venous wall thickness and hoop (circumferential)
      stress, as determined with high-frequency ultrasonography (US), can predict
      cannulation readiness in arteriovenous fistulas (AVFs). MATERIALS AND METHODS:
      Institutional review board approval and informed consent were obtained for this
      prospective study. To determine the US appearance of the venous wall, an AVF
      specimen was excised and scanned in a bath of degassed lactated Ringer solution
      with a 55-MHz probe. The appearance of the wall at high-frequency US was
      correlated with histologic findings. High-frequency (40-55-MHz) US was used to
      image the near-field AVF venous wall of 14 men (mean age, 59 years +/- 11
      [standard deviation]) and six women (mean age, 55 years +/- 14) with newly
      created AVFs within 1 week of cannulation between January 2008 and December 2009.
      Measurements of the intima-media thickness (IMT) were generated by three
      independent observers who were blinded to outcomes. Intraclass correlation
      analysis was performed. Cannulation readiness was defined as no extravasation
      during the first dialysis treatment. RESULTS: By using high-frequency US, the IMT
      was defined as the sum of a thin echogenic blood-intima interface and a uniform
      hypoechoic media. The mean IMT of the no extravasation group (0.16 mm +/- 0.03)
      was greater than that of the extravasation group (0.10 mm +/- 0.02) (P < .001). A
      minimum threshold IMT of 0.13 mm (P < .001) was associated with successful
      cannulation. The mean hoop stress of the no extravasation group (246 kPa +/- 57)
      was lower than that of the extravasation group (530 kPa +/- 199) (P < .001). A
      maximum hoop stress threshold of 248 kPa was associated with successful
      cannulation (P = .009). CONCLUSION: Venous IMT and hoop stress assessed with high
      frequency US can predict cannulation readiness in AVFs that are clinically deemed
      mature.

PMID- 21878615
TI  - Breast cancer: evaluation of response to neoadjuvant chemotherapy with 3.0-T MR
      imaging.
AB  - PURPOSE: To assess how the molecular biomarker status of a breast cancer,
      including human epidermal growth factor receptor 2 (HER2), hormone receptors, and
      the proliferation marker Ki-67 status, affects the diagnosis at 3.0-T magnetic
      resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the
      institutional review board and was HIPAA compliant. Fifty patients (age range, 28
      82 years; mean age, 49 years) receiving neoadjuvant chemotherapy were monitored
      with 3.0-T MR imaging. The longest dimension of the residual cancer was measured
      at MR imaging and correlated with pathologic findings. Patients were further
      divided into subgroups on the basis of HER2, hormone receptor, and Ki-67 status.
      Pathologic complete response (pCR) was defined as when there were no residual
      invasive cancer cells. The Pearson correlation was used to correlate MR imaging
      determined and pathologic tumor size, and the unpaired t test was used to compare
      MR imaging-pathologic size discrepancies. RESULTS: Of the 50 women, 14 achieved
      pCR. There were seven false-negative diagnoses at MR imaging. The overall
      sensitivity, specificity, and accuracy for diagnosing invasive residual disease
      at MR imaging were 81%, 93%, and 84%, respectively. The mean MR imaging
      pathologic size discrepancy was 0.5 cm +/- 0.9 (standard deviation) for HER2
      positive cancer and 2.3 cm +/- 3.5 for HER2-negative cancer (P = .009). In the
      HER2-negative group, the size discrepancy was smaller for hormone receptor
      negative than for hormone receptor-positive cancers (1.0 cm +/- 1.1 vs 3.0 cm +/-
      4.0, P = .04). The size discrepancy was smaller in patients with 40% or greater
      Ki-67 expression (0.8 cm +/- 1.1) than in patients with 10% or less Ki-67
      expression (3.9 cm +/- 5.1, P = .06). CONCLUSION: The diagnostic accuracy of
      breast MR imaging is better in more aggressive than in less aggressive cancers.
      When MR imaging is used for surgical planning, caution should be taken with HER2
      negative hormone receptor-positive cancers.

PMID- 21878616
TI  - Menstrual cycle-related fluctuations in breast density measured by using three
      dimensional MR imaging.
AB  - PURPOSE: To investigate the fluctuation of fibroglandular tissue volume (FV) and
      percentage of breast density (PD) during the menstrual cycle and compare with
      postmenopausal women by using three-dimensional magnetic resonance (MR)-based
      segmentation methods. MATERIALS AND METHODS: This study was approved by the
      Institutional Review Board and was HIPAA compliant. Written informed consent was
      obtained. Thirty healthy female subjects, 24 premenopausal and six
      postmenopausal, were recruited. All subjects underwent MR imaging examination
      each week for 4 consecutive weeks. The breast volume (BV), FV, and PD were
      measured by two operators to evaluate interoperator variation. The fluctuation of
      each parameter measured over the course of the four examinations was evaluated on
      the basis of the coefficient of variation (CV). RESULTS: The results from two
      operators showed a high Pearson correlation for BV (R(2) = 0.99), FV (R(2) =
      0.98), and PD (R(2) = 0.96). The interoperator variation was 3% for BV and around
      5%-6% for FV and PD. In the respective premenopausal and postmenopausal groups,
      the mean CV was 5.0% and 5.6% for BV, 7.6% and 4.2% for FV, and 7.1% and 6.0% for
      PD. The difference between premenopausal and postmenopausal groups was not
      significant (all P values > .05). CONCLUSION: The fluctuation of breast density
      measured at MR imaging during a menstrual cycle was around 7%. The results may
      help the design and interpretation of future studies by using the change of
      breast density as a surrogate marker to evaluate the efficacy of hormone
      modifying drugs for cancer treatment or cancer prevention.

PMID- 21878617
TI  - Biochemical characterization of AtHMA6/PAA1, a chloroplast envelope Cu(I)-ATPase.
AB  - Copper is an essential plant micronutrient playing key roles in cellular
      processes, among them photosynthesis. In Arabidopsis thaliana, copper delivery to
      chloroplasts, mainly studied by genetic approaches, is thought to involve two
      P(IB)-type ATPases: AtHMA1 and AtHMA6/PAA1. The lack of biochemical
      characterization of AtHMA1 and PAA1, and more generally of plant P(IB)-type
      ATPases, is due to the difficulty of getting high amounts of these membrane
      proteins in an active form, either from their native environment or after
      expression in heterologous systems. In this study, we report the first
      biochemical characterization of PAA1, a plant copper-transporting ATPase. PAA1
      produced in Lactococcus lactis is active, forming an aspartyl phosphate
      intermediate in the presence of ATP and the adequate metal ion. PAA1 can also be
      phosphorylated using inorganic phosphate in the absence of transition metal. Both
      phosphorylation types allowed us to demonstrate that PAA1 is activated by
      monovalent copper ions (and to a lower extent by silver ions) with an apparent
      affinity in the micromolar range. In agreement with these biochemical data, we
      also demonstrate that when expressed in yeast, PAA1 induces increased
      sensitivities to copper and silver. These data provide the first enzymatic
      characterization of a P(IB-1)-type plant ATPase and clearly identify PAA1 as a
      high affinity Cu(I) transporter of the chloroplast envelope.

PMID- 21878618
TI  - Identification of human fumarylacetoacetate hydrolase domain-containing protein 1
      (FAHD1) as a novel mitochondrial acylpyruvase.
AB  - The human fumarylacetoacetate hydrolase (FAH) domain-containing protein 1 (FAHD1)
      is part of the FAH protein superfamily, but its enzymatic function is unknown. In
      the quest for a putative enzymatic function of FAHD1, we found that FAHD1
      exhibits acylpyruvase activity, demonstrated by the hydrolysis of acetylpyruvate
      and fumarylpyruvate in vitro, whereas several structurally related compounds were
      not hydrolyzed as efficiently. Conserved amino acids Asp-102 and Arg-106 of FAHD1
      were found important for its catalytic activity, and Mg(2+) was required for
      maximal enzyme activity. FAHD1 was found expressed in all tested murine tissues,
      with highest expression in liver and kidney. FAHD1 was also found in several
      human cell lines, where it localized to mitochondria. In summary, the current
      work identified mammalian FAHD1 as a novel mitochondrial enzyme with acylpyruvate
      hydrolase activity.

PMID- 21878619
TI  - Air1 zinc knuckles 4 and 5 and a conserved IWRXY motif are critical for the
      function and integrity of the Trf4/5-Air1/2-Mtr4 polyadenylation (TRAMP) RNA
      quality control complex.
AB  - In Saccharomyces cerevisiae, non-coding RNAs, including cryptic unstable
      transcripts (CUTs), are subject to degradation by the exosome. The Trf4/5-Air1/2
      Mtr4 polyadenylation (TRAMP) complex in S. cerevisiae is a nuclear exosome
      cofactor that recruits the exosome to degrade RNAs. Trf4/5 are poly(A)
      polymerases, Mtr4 is an RNA helicase, and Air1/2 are putative RNA-binding
      proteins that contain five CCHC zinc knuckles (ZnKs). One central question is how
      the TRAMP complex, especially the Air1/2 protein, recognizes its RNA substrates.
      To characterize the function of the Air1/2 protein, we used random mutagenesis of
      the AIR1/2 gene to identify residues critical for Air protein function. We
      identified air1-C178R and air2-C167R alleles encoding air1/2 mutant proteins with
      a substitution in the second cysteine of ZnK5. Mutagenesis of the second cysteine
      in AIR1/2 ZnK1-5 reveals that Air1/2 ZnK4 and -5 are critical for Air protein
      function in vivo. In addition, we find that the level of CUT, NEL025c, in air1
      ZnK1-5 mutants is stabilized, particularly in air1 ZnK4, suggesting a role for
      Air1 ZnK4 in the degradation of CUTs. We also find that Air1/2 ZnK4 and -5 are
      critical for Trf4 interaction and that the Air1-Trf4 interaction and Air1 level
      are critical for TRAMP complex integrity. We identify a conserved IWRXY motif in
      the Air1 ZnK4-5 linker that is important for Trf4 interaction. We also find that
      hZCCHC7, a putative human orthologue of Air1 that contains the IWRXY motif,
      localizes to the nucleolus in human cells and interacts with both mammalian Trf4
      orthologues, PAPD5 and PAPD7 (PAP-associated domain containing 5 and 7),
      suggesting that hZCCHC7 is the Air component of a human TRAMP complex.

PMID- 21878620
TI  - Expression and characterization of a PNPLA3 protein isoform (I148M) associated
      with nonalcoholic fatty liver disease.
AB  - A genetic variant of PNPLA3 (patatin-like phospholipase domain-containing 3;
      PNPLA3-I148M), a serine protease of unknown function, is associated with
      accumulation of triacylglycerol (TAG) in the liver. To determine the biological
      substrates of PNPLA3 and the effect of the I148M substitution on enzymatic
      activity and substrate specificity, we purified and characterized recombinant
      human PNPLA3 and PNPLA3-I148M. Maximal hydrolytic activity of PNPLA3 was observed
      against the three major glycerolipids, TAG, diacylglycerol, and monoacylglycerol,
      with a strong preference for oleic acid as the acyl moiety. Substitution of
      methionine for isoleucine at position 148 markedly decreased the V(max) of the
      enzyme for glycerolipids but had only a modest effect on the K(m). Purified
      PNPLA3 also catalyzed the hydrolysis of oleoyl-CoA, but the V(max) was 100-fold
      lower for oleoyl-CoA than for triolein. The thioesterase activity required the
      catalytic serine but was only modestly decreased by the I148M substitution. The
      enzyme had little or no hydrolytic activity against the other lipid substrates
      tested, including phospholipids, cholesteryl ester, and retinyl esters. Neither
      the wild-type nor mutant enzyme catalyzed transfer of oleic acid from oleoyl-CoA
      to glycerophosphate, lysophosphatidic acid, or diacylglycerol, suggesting that
      the enzyme does not promote de novo TAG synthesis. Taken together, our results
      are consistent with the notion that PNPLA3 plays a role in the hydrolysis of
      glycerolipids and that the I148M substitution causes a loss of function, although
      we cannot exclude the possibility that the enzyme has additional substrates or
      activities.

PMID- 21878621
TI  - Deletion of betaine-homocysteine S-methyltransferase in mice perturbs choline and
      1-carbon metabolism, resulting in fatty liver and hepatocellular carcinomas.
AB  - Betaine-homocysteine S-methyltransferase (BHMT) uses betaine to catalyze the
      conversion of homocysteine (Hcy) to methionine. There are common genetic
      polymorphisms in the BHMT gene in humans that can alter its enzymatic activity.
      We generated the first Bhmt(-/-) mouse to model the functional effects of
      mutations that result in reduced BHMT activity. Deletion of Bhmt resulted in a 6
      fold increase (p < 0.01) in hepatic and an 8-fold increase (p < 0.01) in plasma
      total Hcy concentrations. Deletion of Bhmt resulted in a 43% reduction in hepatic
      S-adenosylmethionine (AdoMet) (p < 0.01) and a 3-fold increase in hepatic S
      adenosylhomocysteine (AdoHcy) (p < 0.01) concentrations, resulting in a 75%
      reduction in methylation potential (AdoMet:AdoHcy) (p < 0.01). Bhmt(-/-) mice
      accumulated betaine in most tissues, including a 21-fold increase in the liver
      concentration compared with wild type (WT) (p < 0.01). These mice had lower
      concentrations of choline, phosphocholine, glycerophosphocholine,
      phosphatidylcholine, and sphingomyelin in several tissues. At 5 weeks of age,
      Bhmt(-/-) mice had 36% lower total hepatic phospholipid concentrations and a 6
      fold increase in hepatic triacyglycerol concentrations compared with WT (p <
      0.01), which was due to a decrease in the secretion of very low density
      lipoproteins. At 1 year of age, 64% of Bhmt(-/-) mice had visible hepatic tumors.
      Histopathological analysis revealed that Bhmt(-/-) mice developed hepatocellular
      carcinoma or carcinoma precursors. These results indicate that BHMT has an
      important role in Hcy, choline, and one-carbon homeostasis. A lack of Bhmt also
      affects susceptibility to fatty liver and hepatocellular carcinoma. We suggest
      that functional polymorphisms in BHMT that significantly reduce activity may have
      similar effects in humans.

PMID- 21878622
TI  - Interleukin-1beta induces increased transcriptional activation of the
      transforming growth factor-beta-activating integrin subunit beta8 through
      altering chromatin architecture.
AB  - The integrin alphavbeta8 is a cell surface receptor for the latent domain (LAP)
      of the multifunctional cytokine TGF-beta. Through its association with LAP, TGF
      beta is maintained in a latent form that must be activated to function. Binding
      to the integrin alphavbeta8 with subsequent metalloproteolytic cleavage of LAP
      represents a major mechanism of TGF-beta activation in vivo. Altered expression
      of the integrin beta8 subunit (ITGB8) is found in human chronic obstructive
      pulmonary disease, cancers, and brain vascular malformations. We have previously
      shown that the proinflammatory cytokine interleukin-1beta (IL-1beta) increases
      ITGB8 expression on lung fibroblasts, which increases alphavbeta8-mediated TGF
      beta activation in fibrosis and pathologic inflammation. Here we report the
      mechanism of increased ITGB8 expression by IL-1beta. Our data support a model
      where the chromatin architecture of the ITGB8 core promoter is altered by
      nucleosomal repositioning that enhances the interaction of an AP1 complex
      (containing c-Jun and ATF2). This repositioning is caused by the dissociation of
      HDAC2 with the ITGB8 core promoter, leading to increased histone H4 acetylation
      and a loosening of nucleosomal-DNA interactions allowing "opening" of the
      chromatin structure and increased association of c-Jun and ATF-2. These changes
      are mediated through NFkappaB- and p38-dependent pathways. Ultimately, these
      events culminate in increasing ITGB8 transcription, alphavbeta8 surface
      expression, and alphavbeta8-mediated TGFbeta activation.

PMID- 21878624
TI  - Swapping small ubiquitin-like modifier (SUMO) isoform specificity of SUMO
      proteases SENP6 and SENP7.
AB  - SUMO proteases can regulate the amounts of SUMO-conjugated proteins in the cell
      by cleaving off the isopeptidic bond between SUMO and the target protein. Of the
      six members that constitute the human SENP/ULP protease family, SENP6 and SENP7
      are the most divergent members in their conserved catalytic domain. The SENP6 and
      SENP7 subclass displays a clear proteolytic cleavage preference for SUMO2/3
      isoforms. To investigate the structural determinants for such isoform
      specificity, we have identified a unique sequence insertion in the SENP6 and
      SENP7 subclass that is essential for their proteolytic activity and that forms a
      more extensive interface with SUMO during the proteolytic reaction. Furthermore,
      we have identified a region in the SUMO surface determinant for the SUMO2/3
      isoform specificity of SENP6 and SENP7. Double point amino acid mutagenesis on
      the SUMO surface allows us to swap the specificity of SENP6 and SENP7 between the
      two SUMO isoforms. Structure-based comparisons combined with biochemical and
      mutagenesis analysis have revealed Loop 1 insertion in SENP6 and SENP7 as a
      platform to discriminate between SUMO1 and SUMO2/3 isoforms in this subclass of
      the SUMO protease family.

PMID- 21878623
TI  - Allosteric and orthosteric sites in CC chemokine receptor (CCR5), a chimeric
      receptor approach.
AB  - Chemokine receptors play a major role in immune system regulation and have
      consequently been targets for drug development leading to the discovery of
      several small molecule antagonists. Given the large size and predominantly
      extracellular receptor interaction of endogenous chemokines, small molecules
      often act more deeply in an allosteric mode. However, opposed to the well
      described molecular interaction of allosteric modulators in class C 7
      transmembrane helix (7TM) receptors, the interaction in class A, to which the
      chemokine receptors belong, is more sparsely described. Using the CCR5 chemokine
      receptor as a model system, we studied the molecular interaction and
      conformational interchange required for proper action of various orthosteric
      chemokines and allosteric small molecules, including the well known CCR5
      antagonists TAK-779, SCH-C, and aplaviroc, and four novel CCR5 ago-allosteric
      molecules. A chimera was successfully constructed between CCR5 and the closely
      related CCR2 by transferring all extracellular regions of CCR2 to CCR5, i.e. a
      Trojan horse that resembles CCR2 extracellularly but signals through a CCR5
      transmembrane unit. The chimera bound CCR2 (CCL2 and CCL7), but not CCR5
      chemokines (CCL3 and CCL5), with CCR2-like high affinities and potencies
      throughout the CCR5 signaling unit. Concomitantly, high affinity binding of small
      molecule CCR5 agonists and antagonists was retained in the transmembrane region.
      Importantly, whereas the agonistic and antagonistic properties were preserved,
      the allosteric enhancement of chemokine binding was disrupted. In summary, the
      Trojan horse chimera revealed that orthosteric and allosteric sites could be
      structurally separated and still act together with transmission of agonism and
      antagonism across the different receptor units.

PMID- 21878625
TI  - The alpha1 subunit EGL-19, the alpha2/delta subunit UNC-36, and the beta subunit
      CCB-1 underlie voltage-dependent calcium currents in Caenorhabditis elegans
      striated muscle.
AB  - Voltage-gated calcium channels, which play key roles in many physiological
      processes, are composed of a pore-forming alpha1 subunit associated with up to
      three auxiliary subunits. In vertebrates, the role of auxiliary subunits has
      mostly been studied in heterologous systems, mainly because of the severe
      phenotypes of knock-out animals. The genetic model Caenorhabditis elegans has all
      main types of voltage-gated calcium channels and strong loss-of-function
      mutations in all pore-forming and auxiliary subunits; it is therefore a useful
      model to investigate the roles of auxiliary subunits in their native context. By
      recording calcium currents from channel and auxiliary subunit mutants, we
      molecularly dissected the voltage-dependent calcium currents in striated muscle
      of C. elegans. We show that EGL-19 is the only alpha1 subunit that carries
      calcium currents in muscle cells. We then demonstrate that the alpha2/delta
      subunit UNC-36 modulates the voltage dependence, the activation kinetics, and the
      conductance of calcium currents, whereas another alpha2/delta subunit TAG-180 has
      no effect. Finally, we characterize mutants of the two beta subunits, CCB-1 and
      CCB-2. CCB-1 is necessary for viability, and voltage-dependent calcium currents
      are abolished in the absence of CCB-1 whereas CCB-2 does not affect currents.
      Altogether these results show that EGL-19, UNC-36, and CCB-1 underlie voltage
      dependent calcium currents in C. elegans striated muscle.

PMID- 21878626
TI  - Cooperation between an intrinsically disordered region and a helical segment is
      required for ubiquitin-independent degradation by the proteasome.
AB  - The 26 S proteasomal complex, which is responsible for the bulk of protein
      degradation within the cell, recognizes its target substrates via covalently
      linked polyubiquitin moieties. However, a small but growing number of proteasomal
      substrates are degraded without a requirement for ubiquitinylation. One such
      substrate is the pyrimidine biosynthetic enzyme thymidylate synthase (EC
      2.1.1.45), which catalyzes the synthesis of TMP and is the sole de novo source of
      TTP for DNA replication and repair. Previous work showed that intracellular
      proteolysis of human thymidylate synthase is directed by a degron at the
      polypeptide's N-terminal end, composed of an intrinsically disordered region
      (IDR) followed by a highly conserved amphipathic alpha-helix (hA). In the present
      report, we show that the hA helix does not function simply as an extension or
      scaffold for the IDR; rather, it provides a specific structural component that is
      necessary for degradation. Furthermore, its helical conformation is required for
      this function. We demonstrate that small domains from heterologous proteins can
      substitute for the IDR and the hA helix of human thymidylate synthase, indicating
      that the degradation-promoting function of these regions is not sequence
      specific. The results, in general, indicate that cooperation between
      intrinsically disordered domains and alpha-helical segments is required for
      ubiquitin-independent degradation by the proteasome. There appears to be little
      sequence constraint on the ability of these regions to function as degron
      constituents. Rather, it is the overall conformation (or lack thereof) that is
      critical.

PMID- 21878627
TI  - The minimal active structure of human relaxin-2.
AB  - H2 relaxin is a peptide hormone associated with a number of therapeutically
      relevant physiological effects, including regulation of collagen metabolism and
      multiple vascular control pathways. It is currently in phase III clinical trials
      for the treatment of acute heart failure due to its ability to induce
      vasodilation and influence renal function. It comprises 53 amino acids and is
      characterized by two separate polypeptide chains (A-B) that are cross-linked by
      three disulfide bonds. This size and complex structure represents a considerable
      challenge for the chemical synthesis of H2 relaxin, a major limiting factor for
      the exploration of modifications and derivatizations of this peptide, to optimize
      effect and drug-like characteristics. To address this issue, we describe the
      solid phase peptide synthesis and structural and functional evaluation of 24
      analogues of H2 relaxin with truncations at the termini of its peptide chains. We
      show that it is possible to significantly truncate both the N and C termini of
      the B-chain while still retaining potent biological activity. This suggests that
      these regions are not critical for interactions with the H2 relaxin receptor,
      RXFP1. In contrast, truncations do reduce the activity of H2 relaxin for the
      related receptor RXFP2 by improving RXFP1 selectivity. In addition to new
      mechanistic insights into the function of H2 relaxin, this study identifies a
      critical active core with 38 amino acids. This minimized core shows similar
      antifibrotic activity as native H2 relaxin when tested in human BJ3 cells and
      thus represents an attractive receptor-selective lead for the development of
      novel relaxin therapeutics.

PMID- 21878628
TI  - Hck is a key regulator of gene expression in alternatively activated human
      monocytes.
AB  - IL-13 is a Th2 cytokine that promotes alternative activation (M2 polarization) in
      primary human monocytes. Our studies have characterized the functional IL-13
      receptor complex and the downstream signaling events in response to IL-13
      stimulation in alternatively activated monocytes/macrophages. In this report, we
      present evidence that IL-13 induces the activation of a Src family tyrosine
      kinase, which is required for IL-13 induction of M2 gene expression, including 15
      lipoxygenase (15-LO). Our data show that Src kinase activity regulates IL-13
      induced p38 MAPK tyrosine phosphorylation via the upstream kinases MKK3 or MKK6.
      Our findings also reveal that the IL-13 receptor-associated tyrosine kinase Jak2
      is required for the activation of both Src kinase as well as p38 MAPK. Further,
      we found that Src tyrosine kinase-mediated activation of p38 MAPK is required for
      Stat1 and Stat3 serine 727 phosphorylation in alternatively activated
      monocytes/macrophages. Additional studies identify Hck as the specific Src family
      member, stimulated by IL-13 and involved in regulating both p38 MAPK activation
      and p38 MAPK-mediated 15-LO expression. Finally we show that the Hck regulates
      the expression of other alternative state (M2)-specific genes (Mannose receptor,
      MAO-A, and CD36) and therefore conclude that Hck acts as a key regulator
      controlling gene expression in alternatively activated monocytes/macrophages.

PMID- 21878629
TI  - Outer membrane targeting of secretin PulD protein relies on disordered domain
      recognition by a dedicated chaperone.
AB  - Interaction of bacterial outer membrane secretin PulD with its dedicated
      lipoprotein chaperone PulS relies on a disorder-to-order transition of the
      chaperone binding (S) domain near the PulD C terminus. PulS interacts with
      purified S domain to form a 1:1 complex. Circular dichroism, one-dimensional NMR,
      and hydrodynamic measurements indicate that the S domain is elongated and
      intrinsically disordered but gains secondary structure upon binding to PulS.
      Limited proteolysis and mass spectrometry identified the 28 C-terminal residues
      of the S domain as a minimal binding site with low nanomolar affinity for PulS in
      vitro that is sufficient for outer membrane targeting of PulD in vivo. The region
      upstream of this binding site is not required for targeting or multimerization
      and does not interact with PulS, but it is required for secretin function in type
      II secretion. Although other secretin chaperones differ substantially from PulS
      in sequence and secondary structure, they have all adopted at least superficially
      similar mechanisms of interaction with their cognate secretins, suggesting that
      intrinsically disordered regions facilitate rapid interaction between secretins
      and their chaperones.

PMID- 21878630
TI  - N,N'-dinitrosopiperazine-mediated ezrin protein phosphorylation via activation of
      Rho kinase and protein kinase C is involved in metastasis of nasopharyngeal
      carcinoma 6-10B cells.
AB  - N,N'-Dinitrosopiperazine (DNP) is a carcinogen for nasopharyngeal carcinoma
      (NPC), which shows organ specificity to nasopharyngeal epithelium. Herein, we
      demonstrate that DNP induces fiber formation of NPC cells (6-10B) and also
      increases invasion and motility of 6-10B cells. DNP-mediated NPC metastasis also
      was confirmed in nude mice. Importantly, DNP induced the expression of
      phosphorylated ezrin (phos-ezrin) at threonine 567 (Thr-567) dose- and time
      dependently but had no effect on the total ezrin expression at these
      concentrations. Furthermore, DNP-induced phos-ezrin expression was dependent on
      increased Rho kinase and protein kinase C (PKC) activity. DNP may activate Rho
      kinase through binding to its pleckstrin homology and may activate PKC through
      promoting its translocation to the plasma membrane in vivo. DNP-induced phos
      ezrin was associated with induction of fiber growth in 6-10B cells. However, DNP
      could not induce motility and invasion of NPC cells containing ezrin mutated at
      Thr-567. Similarly, DNP could not induce motility and invasion of the cells
      containing siRNAs against Rho or PKC. These results indicate that DNP induces
      ezrin phosphorylation at Thr-567, increases motility and invasion of cells, and
      promotes tumor metastasis. DNP may be involved in NPC metastasis through
      regulation of ezrin phosphorylation at Thr-567.

PMID- 21878632
TI  - 1-Deoxy-D-xylulose 5-phosphate synthase catalyzes a novel random sequential
      mechanism.
AB  - Emerging resistance of human pathogens to anti-infective agents make it necessary
      to develop new agents to treat infection. The methylerythritol phosphate pathway
      has been identified as an anti-infective target, as this essential isoprenoid
      biosynthetic pathway is widespread in human pathogens but absent in humans. The
      first enzyme of the pathway, 1-deoxy-D-xylulose 5-phosphate (DXP) synthase,
      catalyzes the formation of DXP via condensation of D-glyceraldehyde 3-phosphate
      (D-GAP) and pyruvate in a thiamine diphosphate-dependent manner. Structural
      analysis has revealed a unique domain arrangement suggesting opportunities for
      the selective targeting of DXP synthase; however, reports on the kinetic
      mechanism are conflicting. Here, we present the results of tryptophan
      fluorescence binding and kinetic analyses of DXP synthase and propose a new model
      for substrate binding and mechanism. Our results are consistent with a random
      sequential kinetic mechanism, which is unprecedented in this enzyme class.

PMID- 21878631
TI  - Post-translational membrane insertion of tail-anchored transmembrane EF-hand Ca2+
      sensor calneurons requires the TRC40/Asna1 protein chaperone.
AB  - Calneuron-1 and -2 are neuronal EF-hand-type calcium sensor proteins that are
      prominently targeted to trans-Golgi network membranes and impose a calcium
      threshold at the Golgi for phosphatidylinositol 4-OH kinase IIIbeta activation
      and the regulated local synthesis of phospholipids that are crucial for TGN-to
      plasma membrane trafficking. In this study, we show that calneurons are
      nonclassical type II tail-anchored proteins that are post-translationally
      inserted into the endoplasmic reticulum membrane via an association of a 23-amino
      acid-long transmembrane domain (TMD) with the TRC40/Asna1 chaperone complex.
      Following trafficking to the Golgi, calneurons are probably retained in the TGN
      because of the length of the TMD and phosphatidylinositol 4-phosphate lipid
      binding. Both calneurons rapidly self-associate in vitro and in vivo via their
      TMD and EF-hand containing the N terminus. Although dimerization and potentially
      multimerization precludes TRC40/Asna1 binding and thereby membrane insertion, we
      found no evidence for a cytosolic pool of calneurons and could demonstrate that
      self-association of calneurons is restricted to membrane-inserted protein. The
      dimerization properties and the fact that they, unlike every other EF-hand
      calmodulin-like Ca(2+) sensor, are always associated with membranes of the
      secretory pathway, including vesicles and plasma membrane, suggests a high degree
      of spatial segregation for physiological target interactions.

PMID- 21878633
TI  - Forced gating motions by a substituted titratable side chain at the bundle
      crossing of a potassium channel.
AB  - Numerous inwardly rectifying potassium (Kir) channels possess an aromatic residue
      in the helix bundle crossing region, forming the narrowest pore constriction in
      crystal structures. However, the role of the Kir channel bundle crossing as a
      functional gate remains uncertain. We report a unique phenotype of Kir6.2
      channels mutated to encode glutamate at this position (F168E). Despite a
      prediction of four glutamates in close proximity, Kir6.2(F168E) channels are
      predominantly closed at physiological pH, whereas alkalization causes rapid and
      reversible channel activation. These findings suggest that F168E glutamates are
      uncharged at physiological pH but become deprotonated at alkaline pH, forcing
      channel opening due to mutual repulsion of nearby negatively charged side chains.
      The potassium channel pore scaffold likely brings these glutamates close
      together, causing a significant pK(a) shift relative to the free side chain (as
      seen in the KcsA selectivity filter). Alkalization also shifts the apparent ATP
      sensitivity of the channel, indicating that forced motion of the bundle crossing
      is coupled to the ATP-binding site and may resemble conformational changes
      involved in wild-type Kir6.2 gating. The study demonstrates a novel mechanism for
      engineering extrinsic control of channel gating by pH and shows that
      conformational changes in the bundle crossing region are involved in ligand
      dependent gating of Kir channels.

PMID- 21878634
TI  - Cystathionine beta-synthase (CBS) domains 1 and 2 fulfill different roles in
      ionic strength sensing of the ATP-binding cassette (ABC) transporter OpuA.
AB  - The cystathionine beta-synthase module of OpuA in conjunction with an anionic
      membrane surface acts as a sensor of internal ionic strength, which allows the
      protein to respond to osmotic stress. We now show by chemical modification and
      cross-linking studies that CBS2-CBS2 interface residues are critical for
      transport activity and/or ionic regulation of transport, whereas CBS1 serves no
      functional role. We establish that Cys residues in CBS1, CBS2, and the nucleotide
      binding domain are more accessible for cross-linking at high than low ionic
      strength, indicating that these domains undergo conformational changes when
      transiting between the active and inactive state. Structural analyses suggest
      that the cystathionine beta-synthase module is largely unstructured. Moreover, we
      could substitute CBS1 by a linker and preserve ionic regulation of transport.
      These data suggest that CBS1 serves as a linker and the structured CBS2-CBS2
      interface forms a hinge point for ionic strength-dependent rearrangements that
      are transmitted to the nucleotide-binding domain and thereby affect translocation
      activity.

PMID- 21878635
TI  - Group X secreted phospholipase A2 proenzyme is matured by a furin-like proprotein
      convertase and releases arachidonic acid inside of human HEK293 cells.
AB  - Among mammalian secreted phospholipases A(2) (sPLA(2)s), group X sPLA(2) has the
      most potent hydrolyzing activity toward phosphatidylcholine and is involved in
      arachidonic acid (AA) release. Group X sPLA(2) is produced as a proenzyme and
      contains a short propeptide of 11 amino acids ending with a dibasic motif,
      suggesting cleavage by proprotein convertases. Although the removal of this
      propeptide is clearly required for enzymatic activity, the cellular location and
      the protease(s) involved in proenzyme conversion are unknown. Here we have
      analyzed the maturation of group X sPLA(2) in HEK293 cells, which have been
      extensively used to analyze sPLA(2)-induced AA release. Using recombinant mouse
      (PromGX) and human (ProhGX) proenzymes; HEK293 cells transfected with cDNAs
      coding for full-length ProhGX, PromGX, and propeptide mutants; and various
      permeable and non-permeable sPLA(2) inhibitors and protease inhibitors, we
      demonstrate that group X sPLA(2) is mainly converted intracellularly and releases
      AA before externalization from the cell. Most strikingly, the exogenous proenzyme
      does not elicit AA release, whereas the transfected proenzyme does elicit AA
      release in a way insensitive to non-permeable sPLA(2) inhibitors. In transfected
      cells, a permeable proprotein convertase inhibitor, but not a non-permeable one,
      prevents group X sPLA(2) maturation and partially blocks AA release. Mutations at
      the dibasic motif of the propeptide indicate that the last basic residue is
      required and sufficient for efficient maturation and AA release. All together,
      these results argue for the intracellular maturation of group X proenzyme in
      HEK293 cells by a furin-like proprotein convertase, leading to intracellular
      release of AA during secretion.

PMID- 21878636
TI  - Novel membrane-associated androgen receptor splice variant potentiates
      proliferative and survival responses in prostate cancer cells.
AB  - Progression from the androgen-sensitive to androgen-insensitive (or castration
      resistant) stage is the major obstacle for sustained effectiveness of hormonal
      therapy for prostate cancer. The androgen receptor (AR) and its splice variants
      play important roles in regulating the transcription program essential for
      castration resistance. Here, we report the identification of a novel AR splice
      variant, designated as AR8, which is up-regulated in castration-resistant
      prostate cancer cells. AR8 is structurally different from other known AR splice
      variants because it lacks a DNA binding domain and therefore, unlikely functions
      as a transcription factor on its own. Immunofluorescence staining revealed that
      AR8 was primarily localized on the plasma membrane, possibly through
      palmitoylation of two cysteine residues within its unique C-terminal sequence.
      Mutation of these putative palmitoylation sites in AR8 led to loss of its plasma
      membrane localization. In addition, we demonstrated that overexpression of AR8 in
      prostate cancer cells promoted association of Src and AR with the EGF receptor in
      response to EGF treatment and enhanced tyrosine phosphorylation of AR.
      Conversely, specific knockdown of AR8 expression in prostate cancer cells
      compromised EGF-induced Src activation and AR phosphorylation. This effect was
      accompanied with attenuation of proliferation and increased apoptosis in prostate
      cancer cells cultured in androgen-depleted medium. We also showed that AR8 was
      required for optimal transcriptional activity of AR in response to treatment of
      both androgen and EGF. Taken together, our results demonstrate that the membrane
      associated AR8 isoform may contribute to castration resistance by potentiating AR
      mediated proliferative and survival responses to hormones and growth factors.

PMID- 21878637
TI  - MicroRNA-99a inhibits hepatocellular carcinoma growth and correlates with
      prognosis of patients with hepatocellular carcinoma.
AB  - In our in-depth analysis carried out by the Illumina Solexa massive parallel
      signature sequencing, microRNA-99a (miR-99a) was found to be the sixth abundant
      microRNA in the miRNome of normal human liver but was markedly down-regulated in
      hepatocellular carcinoma (HCC). Compelling evidence has suggested the important
      roles of microRNAs in HCC development. However, the biological function of miR
      99a deregulation in HCC remains unknown. In this study, we found that miR-99a was
      remarkably decreased in HCC tissues and cell lines. Importantly, lower miR-99a
      expression in HCC tissues significantly correlated with shorter survival of HCC
      patients, and miR-99a was identified to be an independent predictor for the
      prognosis of HCC patients. Furthermore, restoration of miR-99a dramatically
      suppressed HCC cell growth in vitro by inducing the G(1) phase cell cycle arrest.
      Intratumoral injection of cholesterol-conjugated miR-99a mimics significantly
      inhibited tumor growth and reduced the alpha-fetoprotein level in HCC-bearing
      nude mice. Insulin-like growth factor 1 receptor (IGF-1R) and mammalian target of
      rapamycin (mTOR) were further characterized as the direct targets of miR-99a.
      Furthermore, protein levels of IGF-1R and mTOR were found to be inversely
      correlated with miR-99a expression in HCC tissues. miR-99a mimics inhibited IGF
      1R and mTOR pathways and subsequently suppressed expression of cell cycle-related
      proteins, including cyclin D1 in HCC cells. Conclusively, miR-99a expression was
      frequently down-regulated in HCC tissues and correlates with the prognosis of HCC
      patients, thus proposing miR-99a as a prospective prognosis predictor of HCC. miR
      99a suppresses HCC growth by inducing cell cycle arrest, suggesting miR-99a as
      potential tumor suppressor for HCC therapeutics.

PMID- 21878638
TI  - Phosphorylation and stabilization of topoisomerase IIalpha protein by p38gamma
      mitogen-activated protein kinase sensitize breast cancer cells to its poisons.
AB  - Cancer drugs suppress tumor cell growth by inhibiting specific cellular targets.
      However, most drugs also activate several cellular nonspecific stress pathways,
      and the implications of these off-target effects are mostly unknown. Here, we
      report that p38gamma, but not p38alpha, MAPK is specifically activated by
      treatment of breast cancer cells with topoisomerase II (Topo II) drugs, whereas
      paclitaxel (Taxol) does not have this effect. The activated p38gamma in turn
      phosphorylates and stabilizes Topo IIalpha protein, and this enhances the growth
      inhibition by Topo II drugs. Moreover, p38gamma activity was shown to be
      necessary and sufficient for Topo IIalpha expression, the drug-p38gamma-Topo
      IIalpha axis is only detected in intrinsically sensitive but not resistant cells,
      and p38gamma is co-overexpressed with Topo IIalpha protein in primary breast
      cancers. These results reveal a new paradigm in which p38gamma actively regulates
      the drug-Topo IIalpha signal transduction, and this may be exploited to increase
      the therapeutic activity of Topo II drugs.

PMID- 21878639
TI  - Endogenous APOBEC3B restricts LINE-1 retrotransposition in transformed cells and
      human embryonic stem cells.
AB  - Members of the APOBEC3 (A3) family of cytidine deaminase enzymes act as host
      defense mechanisms limiting both infections by exogenous retroviruses and
      mobilization of endogenous retrotransposons. Previous studies revealed that the
      overexpression of some A3 proteins could restrict engineered human Long
      INterspersed Element-1 (LINE-1 or L1) retrotransposition in HeLa cells. However,
      whether endogenous A3 proteins play a role in restricting L1 retrotransposition
      remains largely unexplored. Here, we show that HeLa cells express endogenous A3B
      and A3C, whereas human embryonic stem cells (hESCs) express A3B, A3C, A3DE, A3F,
      and A3G. To study the relative contribution of endogenous A3 proteins in
      restricting L1 retrotransposition, we first generated small hairpin RNAs (shRNAs)
      to suppress endogenous A3 mRNA expression, and then assessed L1 mobility using a
      cell-based L1 retrotransposition assay. We demonstrate that in both HeLa and
      hESCs, shRNA-based knockdown of A3B promotes a ~2-3.7-fold increase in the
      retrotransposition efficiency of an engineered human L1. Knockdown of the other
      A3s produced no significant increase in L1 activity. Thus, A3B appears to
      restrict engineered L1 retrotransposition in a broad range of cell types,
      including pluripotent cells.

PMID- 21878640
TI  - DNA damage response is suppressed by the high cyclin-dependent kinase 1 activity
      in mitotic mammalian cells.
AB  - DNA damage response (DDR) is vital for genomic stability, and its deficiency is
      linked to tumorigenesis. Extensive studies in interphase (G(1)-S-G(2)) mammalian
      cells have revealed the mechanisms of DDR in great detail; however, how mitotic
      cells respond to DNA damage remains less defined. We report here that a full DDR
      is suppressed in mitotic mammalian cells until telophase/cytokinesis. Although
      early DDR markers such as the phosphorylations of ataxia telangiectasia mutated
      (ATM) and histone H2A.x (H2AX) can be readily detected, the ionizing radiation
      induced foci (IRIF) formation of late DDR markers such as breast cancer type 1
      susceptibility protein (BRCA1) and p53-binding protein 1 (53BP1) are absent until
      the telophase/cytokinesis stage. We further showed that the IR-induced
      ubiquitination cascade around DNA damage sites did not occur in mitotic cells,
      which explains, at least in part, why BRCA1 and 53BP1 cannot be recruited to the
      damaged sites. These observations indicate that DDR is suppressed in mitotic
      cells after the step of gammaH2AX formation. Not surprisingly, we found that the
      absence of a full DDR in mitotic cells was associated with the high cyclin
      dependent kinase 1 (CDK1) activities. More 53BP1 IRIF could be detected when the
      irradiated mitotic cells were treated with a CDK1 inhibitor. Further, the
      activation of CDK5 in interphase cells impedes the formation of 53BP1 IRIF.
      Together, these results suggest that the DDR is suppressed by the high CDK1
      activity in mitotic mammalian cells.

PMID- 21878641
TI  - Tandem translation generates a chaperone for the Salmonella type III secretion
      system protein SsaQ.
AB  - Type III secretion systems (T3SSs) of bacterial pathogens involve the assembly of
      a surface-localized needle complex, through which translocon proteins are
      secreted to form a pore in the eukaryotic cell membrane. This enables the
      transfer of effector proteins from the bacterial cytoplasm to the host cell. A
      structure known as the C-ring is thought to have a crucial role in secretion by
      acting as a cytoplasmic sorting platform at the base of the T3SS. Here, we
      studied SsaQ, an FliN-like putative C-ring protein of the Salmonella
      pathogenicity island 2 (SPI-2)-encoded T3SS. ssaQ produces two proteins by tandem
      translation: a long form (SsaQ(L)) composed of 322 amino acids and a shorter
      protein (SsaQ(S)) comprising the C-terminal 106 residues of SsaQ(L). SsaQ(L) is
      essential for SPI-2 T3SS function. Loss of SsaQ(S) impairs the function of the
      T3SS both ex vivo and in vivo. SsaQ(S) binds to its corresponding region within
      SsaQ(L) and stabilizes the larger protein. Therefore, SsaQ(L) function is
      optimized by a novel chaperone-like protein, produced by tandem translation from
      its own mRNA species.

PMID- 21878642
TI  - KIBRA protein phosphorylation is regulated by mitotic kinase aurora and protein
      phosphatase 1.
AB  - Recent genetic studies in Drosophila identified Kibra as a novel regulator of the
      Hippo pathway, which controls tissue growth and tumorigenesis by inhibiting cell
      proliferation and promoting apoptosis. The cellular function and regulation of
      human KIBRA remain largely unclear. Here, we show that KIBRA is a phosphoprotein
      and that phosphorylation of KIBRA is regulated in a cell cycle-dependent manner
      with the highest level of phosphorylated KIBRA detected in mitosis. We further
      demonstrate that the mitotic kinases Aurora-A and -B phosphorylate KIBRA both in
      vitro and in vivo. We identified the highly conserved Ser(539) as the primary
      phosphorylation site for Aurora kinases. Moreover, we found that wild-type, but
      not catalytically inactive, protein phosphatase 1 (PP1) associates with KIBRA.
      PP1 dephosphorylated Aurora-phosphorylated KIBRA. KIBRA depletion impaired the
      interaction between Aurora-A and PP1. We also show that KIBRA associates with
      neurofibromatosis type 2/Merlin in a Ser(539) phosphorylation-dependent manner.
      Phosphorylation of KIBRA on Ser(539) plays a role in mitotic progression. Our
      results suggest that KIBRA is a physiological substrate of Aurora kinases and
      reveal a new avenue between KIBRA/Hippo signaling and the mitotic machinery.

PMID- 21878643
TI  - The antagonistic action of B56-containing protein phosphatase 2As and casein
      kinase 2 controls the phosphorylation and Gli turnover function of Daz
      interacting protein 1.
AB  - The Hedgehog (Hh) pathway is evolutionarily conserved and plays critical roles
      during embryonic development and adult tissue homeostasis. Defective Hh signaling
      has been linked to a wide range of birth defects and cancers. Hh family proteins
      regulate the expression of their downstream target genes through the control of
      proteolytic processing and the transcriptional activation function of Gli
      transcription factors. Although Hh-dependent regulation of Gli has been studied
      extensively, other Gli regulatory mechanisms remain relatively unappreciated.
      Here we report our identification of a novel signaling cascade that controls the
      stability of Gli proteins. This cascade consists of Daz interacting protein 1
      (Dzip1), casein kinase 2 (CK2), and B56 containing protein phosphatase 2As
      (PP2As). We provide evidence that Dzip1 is involved in a novel Gli turnover
      pathway. We show that CK2 directly phosphorylates Dzip1 at four serine residues,
      Ser-664/665/706/714. B56-containing PP2As, through binding to a domain located
      between amino acid residue 474 and 550 of Dzip1, dephosphorylate Dzip1 on these
      CK2 sites. Our mutagenesis analysis further demonstrates that the
      unphosphorylatable form of Dzip1 is more potent in promoting Gli turnover.
      Consistently, we found that the stability of Gli proteins was decreased upon CK2
      inhibition and increased by inhibition of B56-containing PP2As. Thus, reversible
      phosphorylation of Dzip1, which is controlled by the antagonistic action of CK2
      and B56-containing PP2As, has an important impact on the stability of Gli
      transcription factors and Hh signaling.

PMID- 21878644
TI  - Drug-induced senescence generates chemoresistant stemlike cells with low reactive
      oxygen species.
AB  - Tumor recurrence after chemotherapy or radiation remains a major obstacle to
      successful cancer treatment. A subset of cancer cells, termed cancer stem cells,
      can elude conventional treatments and eventually regenerate a tumor that is more
      aggressive. Despite the large number of studies, molecular events that govern the
      emergence of aggressive therapy-resistant cells with stem cell properties after
      chemotherapy are poorly defined. The present study provides evidence for the rare
      escape of tumor cells from drug-induced cell death, after an intermediate stay in
      a non-cycling senescent stage followed by unstable multiplication characterized
      by spontaneous cell death. However, some cells appear to escape and generate
      stable colonies with an aggressive tumor stem cell-like phenotype. These cells
      displayed higher CD133 and Oct-4 expression. Notably, the drug-selected cells
      that contained low levels of reactive oxygen species (ROS) also showed an
      increase in antioxidant enzymes. Consistent with this in vitro experimental data,
      we observed lower levels of ROS in breast tumors obtained after neoadjuvant
      chemotherapy compared with samples that did not receive preoperative
      chemotherapy. These latter tissues also expressed enhanced levels of ROS defenses
      with enhanced expression of superoxide dismutase. Higher levels of Oct-4 and
      CD133 were also observed in tumors obtained after neoadjuvant chemotherapy.
      Further studies provided evidence for the stabilization of Nrf2 due to reduced 26
      S proteasome activity and increased p21 association as the driving signaling
      event that contributes to the transition from a high ROS quiescent state to a low
      ROS proliferating stage in drug-induced tumor stem cell enrichment.

PMID- 21878645
TI  - Exploiting bacterial glycosylation machineries for the synthesis of a Lewis
      antigen-containing glycoprotein.
AB  - Glycoproteins constitute a class of compounds of increasing importance for
      pharmaceutical applications. The manipulation of bacterial protein glycosylation
      systems from Gram-negative bacteria for the synthesis of recombinant
      glycoproteins is a promising alternative to the current production methods.
      Proteins carrying Lewis antigens have been shown to have potential applications
      for the treatment of diverse autoimmune diseases. In this work, we developed a
      mixed approach consisting of in vivo and in vitro steps for the synthesis of
      glycoproteins containing the Lewis x antigen. Using glycosyltransferases from
      Haemophilus influenzae, we engineered Escherichia coli to assemble a
      tetrasaccharide on the lipid carrier undecaprenylphosphate. This glycan was
      transferred in vivo from the lipid to a carrier protein by the Campylobacter
      jejuni oligosaccharyltransferase PglB. The glycoprotein was then fucosylated in
      vitro by a truncated fucosyltransferase from Helicobacter pylori. Diverse mass
      spectrometry techniques were used to confirm the structure of the glycan. The
      strategy presented here could be adapted in the future for the synthesis of
      diverse glycoproteins. Our experiments demonstrate that bacterial enzymes can be
      exploited for the production of glycoproteins carrying glycans present in human
      cells for potential therapeutic applications.

PMID- 21878646
TI  - Role of the endoplasmic reticulum-associated degradation (ERAD) pathway in
      degradation of hepatitis C virus envelope proteins and production of virus
      particles.
AB  - Viral infections frequently cause endoplasmic reticulum (ER) stress in host cells
      leading to stimulation of the ER-associated degradation (ERAD) pathway, which
      subsequently targets unassembled glycoproteins for ubiquitylation and proteasomal
      degradation. However, the role of the ERAD pathway in the viral life cycle is
      poorly defined. In this paper, we demonstrate that hepatitis C virus (HCV)
      infection activates the ERAD pathway, which in turn controls the fate of viral
      glycoproteins and modulates virus production. ERAD proteins, such as EDEM1 and
      EDEM3, were found to increase ubiquitylation of HCV envelope proteins via direct
      physical interaction. Knocking down of EDEM1 and EDEM3 increased the half-life of
      HCV E2, as well as virus production, whereas exogenous expression of these
      proteins reduced the production of infectious virus particles. Further
      investigation revealed that only EDEM1 and EDEM3 bind with SEL1L, an ER membrane
      adaptor protein involved in translocation of ERAD substrates from the ER to the
      cytoplasm. When HCV-infected cells were treated with kifunensine, a potent
      inhibitor of the ERAD pathway, the half-life of HCV E2 increased and so did virus
      production. Kifunensine inhibited the binding of EDEM1 and EDEM3 with SEL1L, thus
      blocking the ubiquitylation of HCV E2 protein. Chemical inhibition of the ERAD
      pathway neither affected production of the Japanese encephalitis virus (JEV) nor
      stability of the JEV envelope protein. A co-immunoprecipitation assay showed that
      EDEM orthologs do not bind with JEV envelope protein. These findings highlight
      the crucial role of the ERAD pathway in the life cycle of specific viruses.

PMID- 21878647
TI  - Staphylococcus aureus protein A mediates invasion across airway epithelial cells
      through activation of RhoA GTPase signaling and proteolytic activity.
AB  - Staphyococcus aureus and especially the epidemic methicillin-resistant S. aureus
      strains cause severe necrotizing pneumonia. The mechanisms whereby these
      organisms invade across the mucosal epithelial barrier to initiate invasive
      infection are not well understood. Protein A (SpA), a highly conserved and
      abundant surface protein of S. aureus, activates TNF receptor 1 and EGF receptor
      (EGFR) signaling cascades that can perturb the cytoskeleton. We demonstrate that
      wild-type S. aureus, but not spa mutants, invade across polarized airway
      epithelial cell monolayers via the paracellular junctions. SpA stimulated a
      RhoA/ROCK/MLC cascade, resulting in the contraction of the cytoskeleton. SpA(+)
      but not SpA(-) mutants stimulated activation of EGFR and along with subsequent
      calpain activity cleaved the membrane-spanning junctional proteins occludin and E
      cadherin, facilitating staphylococcal transmigration through the cell-cell
      junctions. Treatment of polarized human airway epithelial monolayers with
      inhibitors of ROCK, EGFR, MAPKs, or calpain prevented staphylococcal penetration
      through the monolayers. In vivo, blocking calpain activity impeded bacterial
      invasion into the lung parenchyma. Thus, S. aureus exploits multiple receptors
      available on the airway mucosal surface to facilitate invasion across epithelial
      barriers.

PMID- 21878648
TI  - Chemokine CXCL12 uses CXCR4 and a signaling core formed by bifunctional Akt,
      extracellular signal-regulated kinase (ERK)1/2, and mammalian target of rapamycin
      complex 1 (mTORC1) proteins to control chemotaxis and survival simultaneously in
      mature dendritic cells.
AB  - Chemokines control several cell functions in addition to chemotaxis. Although
      much information is available on the involvement of specific signaling molecules
      in the control of single functions controlled by chemokines, especially
      chemotaxis, the mechanisms used by these ligands to regulate several cell
      functions simultaneously are completely unknown. Mature dendritic cells (maDCs)
      migrate through the afferent lymphatic vessels to the lymph nodes, where they
      regulate the initiation of the immune response. As maDCs are exposed to chemokine
      CXCL12 (receptors CXCR4 and CXCR7) during their migration, its functions are
      amenable to be regulated by this ligand. We have used maDCs as a model system to
      analyze the mechanisms whereby CXCL12 simultaneously controls chemotaxis and
      survival in maDCs. We show that CXCL12 uses CXCR4, but not CXCR7, and the
      components of a signaling core that includes G(i)/Gbetagamma, PI3K-alpha/-delta/
      gamma, Akt, ERK1/2 and mammalian target of rapamycin complex 1 (mTORC1), which
      organize hierarchically to control both functions. Downstream of Akt, Forkhead
      box class O (FOXO) regulates CXCL12-dependent survival, but not chemotaxis,
      suggesting that downstream of the aforementioned signaling core, additional
      signaling molecules may control more selectively CXCL12-dependent chemotaxis or
      survival. Finally, the data obtained also show that CXCR4 uses a signaling
      signature that is different from that used by CCR7 to control similar functions.

PMID- 21878650
TI  - miR-497 and miR-302b regulate ethanol-induced neuronal cell death through BCL2
      protein and cyclin D2.
AB  - In chronic alcoholism, brain shrinkage and cognitive defects because of neuronal
      death are well established, although the sequence of molecular events has not
      been fully explored yet. We explored the role of microRNAs (miRNAs) in ethanol
      induced apoptosis of neuronal cells. Ethanol-sensitive miRNAs in SH-SY5Y, a human
      neuroblastoma cell line, were identified using real-time PCR-based TaqMan low
      density arrays. Long-term exposure to ethanol (0.5% v/v for 72 h) produced a
      maximum increase in expression of miR-497 (474-fold) and miR-302b (322-fold).
      Similar to SH-SY5Y, long-term exposure to ethanol induced miR-497 and miR-302b in
      IMR-32, another human neuroblastoma cell line. Using in silico approaches, BCL2
      and cyclin D2 (CCND2) were identified as probable target genes of these miRNAs.
      Cotransfection studies with 3'-UTR of these genes and miRNA mimics have
      demonstrated that BCL2 is a direct target of miR-497 and that CCND2 is regulated
      negatively by either miR-302b or miR-497. Overexpression of either miR-497 or miR
      302b reduced expression of their identified target genes and increased caspase 3
      mediated apoptosis of SH-SY5Y cells. However, overexpression of only miR-497
      increased reactive oxygen species formation, disrupted mitochondrial membrane
      potential, and induced cytochrome c release (mitochondria-related events of
      apoptosis). Moreover, ethanol induced changes in miRNAs, and their target genes
      were substantially prevented by pre-exposure to GSK-3B inhibitors. In conclusion,
      our studies have shown that ethanol-induced neuronal apoptosis follows both the
      mitochondria-mediated (miR-497- and BCL2-mediated) and non-mitochondria-mediated
      (miR-302b- and CCND2-mediated) pathway.

PMID- 21878649
TI  - The Azoarcus group I intron ribozyme misfolds and is accelerated for refolding by
      ATP-dependent RNA chaperone proteins.
AB  - Structured RNAs traverse complex energy landscapes that include valleys
      representing misfolded intermediates. In Neurospora crassa and Saccharomyces
      cerevisiae, efficient splicing of mitochondrial group I and II introns requires
      the DEAD box proteins CYT-19 and Mss116p, respectively, which promote folding
      transitions and function as general RNA chaperones. To test the generality of RNA
      misfolding and the activities of DEAD box proteins in vitro, here we measure
      native folding of a small group I intron ribozyme from the bacterium Azoarcus by
      monitoring its catalytic activity. To develop this assay, we first measure
      cleavage of an oligonucleotide substrate by the prefolded ribozyme. Substrate
      cleavage is rate-limited by binding and is readily reversible, with an internal
      equilibrium near unity, such that the amount of product observed is less than the
      amount of native ribozyme. We use this assay to show that approximately half of
      the ribozyme folds readily to the native state, whereas the other half forms an
      intermediate that transitions slowly to the native state. This folding transition
      is accelerated by urea and increased temperature and slowed by increased Mg(2+)
      concentration, suggesting that the intermediate is misfolded and must undergo
      transient unfolding during refolding to the native state. CYT-19 and Mss116p
      accelerate refolding in an ATP-dependent manner, presumably by disrupting
      structure in the intermediate. These results highlight the tendency of RNAs to
      misfold, underscore the roles of CYT-19 and Mss116p as general RNA chaperones,
      and identify a refolding transition for further dissection of the roles of DEAD
      box proteins in RNA folding.

PMID- 21878651
TI  - Loss of Rpt5 protein interactions with the core particle and Nas2 protein causes
      the formation of faulty proteasomes that are inhibited by Ecm29 protein.
AB  - The proteasome is a large and complex protease formed by 66 polypeptides. The
      assembly of the proteasome is assisted by at least nine chaperones. One of these
      chaperones, Nas2/p27, binds to the C-terminal region of the AAA-ATPase Rpt5. We
      report here that the tail of Rpt5 provides two functions. First, it facilitates
      the previously reported interaction with the proteasome core particle (CP).
      Second, it is essential for the interaction with Nas2. Deletion of the C-terminal
      amino acid of Rpt5 disrupts the CP interaction, but not the binding to Nas2. The
      latter is surprising considering Nas2 contains a PDZ domain, which is often
      involved in binding to C termini. Interestingly, deletion of the last three amino
      acids interferes with both functions. The disruption of the Rpt5-CP interactions
      gave distinct phenotypes different from disruption of the Nas2-Rpt5 interaction.
      Additionally, proteasomes purified from a Saccharomyces cerevisiae rpt5-Delta3
      strain show a strong enrichment of Ecm29. The function of Ecm29, a proteasome
      associated protein, is not well understood. Our data show that Ecm29 can inhibit
      proteasomes, because our Ecm29-containing proteasomes have reduced suc-LLVY-AMC
      hydrolytic activity. Consistent with this apparent role as negative regulator,
      the deletion of ECM29 rescues the phenotypes of rpt5-Delta3 and nas2Delta in an
      hsm3Delta background. In sum, the interactions facilitated by the tail of Rpt5
      act synergistically to minimize the formation of faulty proteasomes, thereby
      preventing recognition and inhibition by Ecm29.

PMID- 21878652
TI  - Structural defects in the regulatory particle-core particle interface of the
      proteasome induce a novel proteasome stress response.
AB  - Proteasomes consist of a 19-subunit regulatory particle (RP) and 28-subunit core
      particle (CP), an alpha(7)beta(7)beta(7)alpha(7) structure. The RP recognizes
      substrates and translocates them into the CP for degradation. At the RP-CP
      interface, a heterohexameric Rpt ring joins to a heteroheptameric CP alpha ring.
      Rpt C termini insert individually into the alpha ring pockets to form a salt
      bridge with a pocket lysine residue. We report that substitutions of alpha pocket
      lysine residues produce an unexpected block to CP assembly, arising from a late
      stage defect in beta ring assembly. Substitutions alpha5(K66A) and alpha6(K62A)
      resulted in abundant incorporation of immature CP beta subunits, associated with
      a complete beta ring, into proteasome holoenzymes. Incorporation of immature CP
      into the proteasome depended on a proteasome-associated protein, Ecm29. Using
      ump1 mutants, we identified Ecm29 as a potent negative regulator of RP assembly
      and confirmed our previous findings that proper RP assembly requires the CP.
      Ecm29 was enriched on proteasomes of pocket lysine mutants, as well as those of
      rpt4-Delta1 and rpt6-Delta1 mutants, in which the C-terminal residue, thought to
      contact the pocket lysine, is deleted. In both rpt6-Delta1 and alpha6(K62A)
      proteasomes, Ecm29 suppressed opening of the CP substrate translocation channel,
      which is gated through interactions between Rpt C termini and the alpha pockets.
      The ubiquitin ligase Hul5 was recruited to these proteasomes together with Ecm29.
      Proteasome remodeling through the addition of Ecm29 and Hul5 suggests a new layer
      of the proteasome stress response and may be a common response to structurally
      aberrant proteasomes or deficient proteasome function.

PMID- 21878653
TI  - Identification of a chitinase-modifying protein from Fusarium verticillioides:
      truncation of a host resistance protein by a fungalysin metalloprotease.
AB  - Chitinase-modifying proteins (cmps) are proteases secreted by fungal pathogens
      that truncate the plant class IV chitinases ChitA and ChitB during maize ear rot.
      cmp activity has been characterized for Bipolaris zeicola and Stenocarpella
      maydis, but the identities of the proteases are not known. Here, we report that
      cmps are secreted by multiple species from the genus Fusarium, that cmp from
      Fusarium verticillioides (Fv-cmp) is a fungalysin metalloprotease, and that it
      cleaves within a sequence that is conserved in class IV chitinases. Protein
      extracts from Fusarium cultures were found to truncate ChitA and ChitB in vitro.
      Based on this activity, Fv-cmp was purified from F. verticillioides. N-terminal
      sequencing of truncated ChitA and MALDI-TOF-MS analysis of reaction products
      showed that Fv-cmp is an endoprotease that cleaves a peptide bond on the C
      terminal side of the lectin domain. The N-terminal sequence of purified Fv-cmp
      was determined and compared with a set of predicted proteins, resulting in its
      identification as a zinc metalloprotease of the fungalysin family. Recombinant Fv
      cmp also truncated ChitA, confirming its identity, but had reduced activity,
      suggesting that the recombinant protease did not mature efficiently from its
      propeptide-containing precursor. This is the first report of a fungalysin that
      targets a nonstructural host protein and the first to implicate this class of
      virulence-related proteases in plant disease.

PMID- 21878654
TI  - The role of autophagy in cancer: therapeutic implications.
AB  - Autophagy is a homeostatic, catabolic degradation process whereby cellular
      proteins and organelles are engulfed by autophagosomes, digested in lysosomes,
      and recycled to sustain cellular metabolism. Autophagy has dual roles in cancer,
      acting as both a tumor suppressor by preventing the accumulation of damaged
      proteins and organelles and as a mechanism of cell survival that can promote the
      growth of established tumors. Tumor cells activate autophagy in response to
      cellular stress and/or increased metabolic demands related to rapid cell
      proliferation. Autophagy-related stress tolerance can enable cell survival by
      maintaining energy production that can lead to tumor growth and therapeutic
      resistance. As shown in preclinical models, inhibition of autophagy restored
      chemosensitivity and enhanced tumor cell death. These results established
      autophagy as a therapeutic target and led to multiple early phase clinical trials
      in humans to evaluate autophagy inhibition using hydroxychloroquine in
      combination with chemotherapy or targeted agents. Targeting autophagy in cancer
      will provide new opportunities for drug development, because more potent and
      specific inhibitors of autophagy are needed. The role of autophagy and its
      regulation in cancer cells continues to emerge, and studies aim to define optimal
      strategies to modulate autophagy for therapeutic advantage.

PMID- 21878655
TI  - Inactivation of mirk/dyrk1b kinase targets quiescent pancreatic cancer cells.
AB  - A major problem in the treatment of cancer arises from quiescent cancer cells
      that are relatively insensitive to most chemotherapeutic drugs and radiation.
      Such residual cancer cells can cause tumor regrowth or recurrence when they
      reenter the cell cycle. Earlier studies showed that levels of the
      serine/theronine kinase Mirk/dyrk1B are elevated up to 10-fold in quiescent G(0)
      tumor cells. Mirk uses several mechanisms to block cell cycling, and Mirk
      increases expression of antioxidant genes that decrease reactive oxygen species
      (ROS) levels and increase quiescent cell viability. We now show that a novel
      small molecule Mirk kinase inhibitor blocked tumor cells from undergoing
      reversible arrest in a quiescent G(0) state and enabled some cells to exit
      quiescence. The inhibitor increased cycling in Panc1, AsPc1, and SW620 cells that
      expressed Mirk, but not in HCT116 cells that did not. Mirk kinase inhibition
      elevated ROS levels and DNA damage detected by increased phosphorylation of the
      histone protein H2AX and by S-phase checkpoints. The Mirk kinase inhibitor
      increased cleavage of the apoptotic proteins PARP and caspase 3, and increased
      tumor cell kill several-fold by gemcitabine and cisplatin. A phenocopy of these
      effects occurred following Mirk depletion, showing drug specificity. In previous
      studies Mirk knockout or depletion had no detectable effect on normal tissue,
      suggesting that the Mirk kinase inhibitor could have a selective effect on cancer
      cells expressing elevated levels of Mirk kinase.

PMID- 21878656
TI  - Antitumoral effects of calcitriol in basal cell carcinomas involve inhibition of
      hedgehog signaling and induction of vitamin D receptor signaling and
      differentiation.
AB  - Activation of the Hedgehog (Hh)-signaling pathway due to deficiency in the Hh
      receptor Patched1 (Ptch) is the pivotal defect leading to formation of basal cell
      carcinoma (BCC). Recent reports provided evidence of Ptch-dependent secretion of
      vitamin D(3)-related compound, which functions as an endogenous inhibitor of Hh
      signaling by repressing the activity of the signal transduction partner of Ptch,
      Smoothened (Smo). This suggests that Ptch-deficient tumor cells are devoid of
      this substance, which in turn results in activation of Hh-signaling. Here, we
      show that the application of the physiologically active form of vitamin D(3),
      calcitriol, inhibits proliferation and growth of BCC of Ptch mutant mice in vitro
      and in vivo. This is accompanied by the activation of the vitamin D receptor
      (Vdr) and induction of BCC differentiation. In addition, calcitriol inhibits Hh
      signaling at the level of Smo in a Vdr-independent manner. The concomitant
      antiproliferative effects on BCC growth are stronger than those of the Hh
      specific inhibitor cyclopamine, even though the latter more efficiently inhibits
      Hh signaling. Taken together, we show that exogenous supply of calcitriol
      controls the activity of 2 independent pathways, Hh and Vdr signaling, which are
      relevant to tumorigenesis and tumor treatment. These data suggest that calcitriol
      could be a therapeutic option in the treatment of BCC, the most common tumor in
      humans.

PMID- 21878658
TI  - Drug-related problems detected in Australian Community Pharmacies: The PROMISe
      Trial.
AB  - BACKGROUND: Drug-related problems (DRPs) are a major burden on health care
      systems. Community pharmacists are ideally placed to detect, prevent, and resolve
      these DRPs. OBJECTIVE: To determine the number and nature of DRPs detected and
      clinical interventions performed by Australian community pharmacists, using an
      electronic system. METHODS: An electronic documentation system was designed and
      integrated into the existing dispensing software of 186 pharmacies to allow
      pharmacists to record details about the clinical interventions they performed to
      prevent or resolve DRPs. Participating pharmacies were randomly allocated to 3
      groups: group 1 had documentation software, group 2 had documentation software
      plus a timed reminder to document interventions, and group 3 had documentation
      software, a timed reminder, and an electronic decision support prompt.
      Pharmacists classified DRPs, entered recommendations they made, and estimated the
      clinical significance of the intervention. An observational substudy that
      included pharmacies without any documentation software was completed to verify
      intervention rates. RESULTS: Over 12 weeks, 531 participating pharmacists
      recorded 6230 clinical interventions from 2,013,923 prescriptions, with a median
      intervention rate of 0.23% of prescriptions. No significant differences were seen
      between the 3 groups that used documentation software; as expected, however, the
      pharmacies that used this software had a significantly higher documentation rate
      compared to the pharmacies without documentation software. The most common
      interventions were related to drug selection problems (30.8%) and educational
      issues (24.4%). Recommendations were often related to a change in therapy
      (40.0%), and 41.6% of interventions were self-rated as highly significant. Drug
      groups most commonly subject to an intervention included antibiotics,
      glucocorticoids, nonsteroidal antiinflammatory drugs, and opioids. CONCLUSIONS:
      The documentation system allowed for the determination of the frequency and types
      of DRPs, as well as the recommendations made to resolve them in community
      pharmacy practice. Use of the software, including its electronic prompts,
      significantly increased the documentation of interventions by pharmacists.

PMID- 21878657
TI  - Activation of the insulin-like growth factor-1 receptor induces resistance to
      epidermal growth factor receptor antagonism in head and neck squamous carcinoma
      cells.
AB  - Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have
      poor efficacy in head and neck squamous carcinoma cells (HNSCC). Because the IGF
      1 receptor (IGF1R) generates potent prosurvival signals and has been implicated
      in therapeutic resistance, its ability to induce resistance to EGFR-TKIs was
      studied in vitro. Five HNSCC cell lines showed reduced sensitivity to the EGFR
      TKI gefitinib when the IGF1R was activated. In SCC-25 and Cal27 cells, gefitinib
      inhibited basal and EGF-stimulated EGFR, extracellular signal-regulated kinase
      (Erk), and Akt phosphorylation and reduced cell number. This correlated with
      initiation of apoptosis based on a 4-fold increase in PARP cleavage and a 2.5
      fold increase in Annexin V positivity. The apoptotic response and reduction in
      cell number were blocked by IGF1R activation, which resulted in phosphorylation
      of both Erk and Akt. In both the cell lines, IGF1R-induced Erk, but not Akt,
      activation was eliminated by gefitinib. IGF1R-induced gefitinib resistance was
      unaffected by MAP/Erk kinase inhibition with U0126 but was partially impaired by
      inhibition of phosphoinositide-3-kinase with LY294002. The IGF1R-TKI PQ401
      inhibited growth of SCC-25 and Cal27 cells alone and also acted synergistically
      with gefitinib. Thus, the IGF1R can make HNSCC cells resistant to EGFR-TKI
      treatment via a prosurvival mechanism. Of the 8 HNSCC tumor samples studied, all
      samples expressed the IGF1R and 5 showed detectable IGF1R phosphorylation,
      suggesting that this receptor may be relevant in vivo, and thus, combined
      EGFR/IGF1R inhibition may be necessary in some patients for effective targeted
      molecular therapy.

PMID- 21878659
TI  - Budesonide for the treatment of autoimmune hepatitis.
AB  - OBJECTIVE: To evaluate the use of budesonide for the treatment of autoimmune
      hepatitis (AIH). DATA SOURCES: Literature was accessed through PubMed/MEDLINE
      (1966-June 2011) and Web of Science (1965-June 2011) using the terms autoimmune
      hepatitis and budesonide. Literature was limited to English-language
      publications. In addition, references from publications identified were reviewed.
      STUDY SELECTION AND DATA EXTRACTION: All articles in English identified from the
      data sources were evaluated. DATA SYNTHESIS: The initial treatment of choice for
      AIH is prednisone alone or with azathioprine. However, a significant number of
      patients do not respond adequately or have adverse reactions to this regimen;
      therefore, alternative treatments are required. Budesonide is an orally
      administered synthetic corticosteroid with high affinity for the glucocorticoid
      receptor that undergoes extensive first-pass metabolism. It has Food and Drug
      Administration-approved labeling for the treatment and maintenance of remission
      of mild-to-moderate Crohn disease involving the ileum and/or ascending colon. One
      prospective, active-controlled study of budesonide in the treatment of AIH was
      identified, as well as 5 small open-label studies and 1 retrospective chart
      review. Budesonide appears to have efficacy in the treatment of AIH, including in
      patients intolerant to standard therapy with prednisone alone or with
      azathioprine, with a reduced incidence of corticosteroid-related adverse
      reactions. However, in patients with AIH and cirrhosis, the efficacy of
      budesonide may be reduced and the incidence of corticosteroid-related adverse
      reactions may be increased. CONCLUSIONS: Budesonide may be an additional
      treatment option for patients with AIH but without cirrhosis who are intolerant
      to standard therapy with prednisone or prednisone with azathioprine.

PMID- 21878660
TI  - Neuroleptic malignant syndrome versus serotonin syndrome: the search for a
      diagnostic tool.
AB  - OBJECTIVE: To evaluate the use of urine dopamine and catecholamine concentrations
      as diagnostic aids in a patient with neuroleptic malignant syndrome (NMS) in the
      emergency department setting. CASE SUMMARY: A 61-year-old female on multiple
      medications, including several antipsychotics, rapidly deteriorated, with fever,
      lead-pipe rigidity, and decreased level of consciousness. The patient died 20
      days after initial presentation to an emergency department. The Naranjo
      probability scale indicated probable causality for NMS due to quetiapine,
      haloperidol, and risperidone in this patient, whereas the Naranjo scale assigned
      only possible causality for serotonin syndrome developing with serotonergic
      agents. Laboratory investigations of blood and urine revealed elevations in
      dopamine, metanephrines, and epinephrines, as well as trazodone and risperidone.
      Serotonin metabolites were not elevated. DISCUSSION: NMS is a rare and
      potentially severe adverse effect associated with the use of antipsychotic
      medications. It is mainly characterized by hyperthermia, altered mental state,
      hemodynamic dysregulation, elevated serum creatine kinase, and rigors. It has
      been associated with multisystem organ failure potentially leading to
      rhabdomyolysis, acute respiratory distress syndrome, and disseminated
      intravascular coagulation. The prevalence of this syndrome is associated with the
      use of neuroleptics. Serotonin syndrome is another adverse drug reaction leading
      to NMS associated with elevated serotonin. It occurs when multiple serotonergic
      medications are ingested and is associated with rapid onset of altered mental
      status, myoclonus, and autonomic instability. Differentiating between NMS and
      serotonin syndrome can be challenging because of their similar clinical
      presentation. This case highlights the importance of a diagnostic aid being
      available to help distinguish between the 2 syndromes. CONCLUSIONS: We propose
      that laboratory findings that include dopamine and serotonin metabolites can be
      used as adjuncts to clinical and prescription histories in the diagnosis of NMS.
      The use of urinary catecholamine as a diagnostic aid in NMS needs further
      evaluation.

PMID- 21878661
TI  - Sunitinib induces apoptosis in pheochromocytoma tumor cells by inhibiting
      VEGFR2/Akt/mTOR/S6K1 pathways through modulation of Bcl-2 and BAD.
AB  - Sunitinib is an oral multitargeted receptor tyrosine kinase inhibitor with
      antiangiogenic and antitumor activity that mainly targets vascular endothelial
      growth factor receptors (VEGFRs). Very recently, sunitinib has been shown to be
      an active agent for the treatment of malignant pheochromocytomas. However, it is
      unclear whether sunitinib acts only through an antiangiogenic mechanism or
      whether it may also directly target tumor cells. Sunitinib markedly induced
      apoptosis of PC12 cells in a dose-dependent and time-dependent manner.
      Furthermore, in support of these findings, we found that sunitinib induced a
      reduction in the expression of the antiapoptotic molecule Bcl-2 as well as
      dephosphorylation of the proapoptotic molecule BAD, which results in the
      activation of BAD in these cells. Consistent with these apoptotic effects, our
      results showed that sunitinib inhibited phosphorylation of Akt and mTOR and was
      followed by a reduction of S6K1, which is a well-known target of mTOR. Knockdown
      of VEGFR-2 attenuated the sunitinib-induced effects, including apoptosis and
      inhibition of signaling pathways such as the phosphorylation of Akt as well as
      mTOR, and Bcl-2, which confirmed that these effects could be mediated by VEGFR-2.
      In addition, silencing of S6K1 induced apoptosis accompanied by a decrease in the
      phosphorylation of BAD and Bcl-2, similar to that observed with sunitinib
      treatment. Thus, these results together suggest that sunitinib initially exerts
      its apoptotic effect through the inhibition of VEGFR-2, which, when followed by
      reduction of its downstream effectors, including Akt/mTOR/S6K1, may lead to
      inhibition of the antiapoptotic molecule Bcl-2 and activation of the proapoptotic
      molecule BAD in PC12 cells. However, PC12 cells do not precisely reflect the
      pathogenesis of malignant cells. Therefore, we confirmed the key findings by
      replicating these experiments in human neuroblastoma SK-N-SH cells.

PMID- 21878662
TI  - Conditional disruption of IGF-I gene in type 1alpha collagen-expressing cells
      shows an essential role of IGF-I in skeletal anabolic response to loading.
AB  - To establish a causal role for locally produced IGF-I in the mechanical strain
      response in the bone, we have generated mice with conditional disruption of the
      insulin-like growth factor (IGF) I gene in type 1alpha(2) collagen-expressing
      cells using the Cre-loxP approach. At 10 wk of age, loads adjusted to account for
      bone size difference were applied via four-point bending or axial loading (AL) in
      mice. Two wk of bending and AL produced significant increases in bone mineral
      density and bone size at the middiaphysis of wild-type (WT), but not knockout
      (KO), mice. In addition, AL produced an 8-25% increase in trabecular parameters
      (bone volume-tissue volume ratio, trabecular thickness, and trabecular bone
      mineral density) at the secondary spongiosa of WT, but not KO, mice.
      Histomorphometric analysis at the trabecular site revealed that AL increased
      osteoid width by 60% and decreased tartrate-resistance acidic phosphatase-labeled
      surface by 50% in the WT, but not KO, mice. Consistent with the in vivo data,
      blockade of IGF-I action with inhibitory IGF-binding protein (IGFBP4) in vitro
      completely abolished the fluid flow stress-induced MC3T3-E1 cell proliferation.
      One-way ANOVA revealed that expression levels of EFNB1, EFNB2, EFNA2, EphB2, and
      NR4a3 were different in the loaded bones of WT vs. KO mice and may, in part, be
      responsible for the increase in bone response to loading in the WT mice. In
      conclusion, IGF-I expressed in type 1 collagen-producing bone cells is critical
      for converting mechanical signal to anabolic signal in bone, and other growth
      factors cannot compensate for the loss of local IGF-I.

PMID- 21878663
TI  - Polyphenols, isothiocyanates, and carotenoid derivatives enhance estrogenic
      activity in bone cells but inhibit it in breast cancer cells.
AB  - While exposure to estrogens is a major risk factor of breast and endometrial
      cancer, it well established that estrogens are beneficial for bone health. We
      have previously shown that carotenoids inhibit estrogen signaling in breast and
      endometrial cancer cells. The aim of this study was to compare the effects of
      various phytonutrients, (carotenoid derivatives, polyphenols, isothiocyanates) on
      estrogenic activity in breast cancer cells and osteoblast-like cells. All the
      tested phytonutrients inhibited estrogen response element (ERE) transactivation
      in breast cancer cells. In contrast, these compounds either did not affect or
      enhanced ERE activity and the expression of several bone-forming genes. These
      results were obtained using two osteoblast-like cell lines, MG-63 human
      osteosarcoma cells stably transfected with estrogen receptor-alpha (ERalpha) and
      MC3T3-E1 mouse calvaria-derived cells expressing endogenous ER. Phytonutrients
      induced ERE inhibition in breast cancer cells, and its potentiation in osteoblast
      like cells were associated both with a decrease and a rise in total and nuclear
      ERalpha levels, respectively. Phytonutrients activated the
      electrophile/antioxidant response element (EpRE/ARE) transcription system to
      various extents in both cancer and bone cell lines. Overexpression of Nrf2, the
      major EpRE/ARE activating transcription factor, mimicked the effects of
      phytonutrients, causing inhibition and enhancement of ERE transactivation in
      breast cancer cells and in osteoblast-like cells, respectively. Moreover,
      reduction in Nrf2 levels by RNAi led to a decrease in the phytonutrient
      potentiation of ERE activity transactivation in osteoblast-like cells. These
      findings suggest that the enhancement and inhibition of estrogen signaling by
      phytonutrients in bone-derived cells and breast cancer cells, respectively, is
      partially mediated by the activation of the Nrf2/ARE system.

PMID- 21878664
TI  - A defect in Nrf2 signaling constitutes a mechanism for cellular stress
      hypersensitivity in a genetic rat model of type 2 diabetes.
AB  - Nrf2 regulates the expression and coordinated induction of a battery of
      antioxidant phase 2 genes that protect cells against the cumulative damaging
      effects of oxidative stress (OS), a major contributor in the development of
      chronic diabetic complications. Using cultured dermal fibroblasts from rats with
      type 2 diabetes (DFs), we investigated the intracellular redox status and the
      adaptive response to OS, in which Nrf2 plays a central role. Our data confirmed
      that the generation of superoxide by NADPH oxidase and the mitochondria was
      enhanced in DFs compared with corresponding controls. This was associated with a
      decrease in the antioxidant capacity and an increase in the sensitivity of these
      DFs to hydrogen peroxide-induced necrotic cell death. Nrf2 levels in total cell
      extracts were diminished, and this abnormality appears to stem from a diabetes
      related decrease in Nrf2 protein stability. Endogenous (oligomycin) and exogenous
      (tert-butylhydroquinone) induction of OS enhanced the nuclear translocation of
      Nrf2 and increased the mRNA expression of Nrf2-sensitive genes in control but not
      DFs. The activity of the GSK-3beta/Fyn axis was increased markedly in DFs when
      compared with the corresponding controls. Chemical inhibition of GSK-3beta
      mitigated the diabetes-related suppression of the OS-induced nuclear accumulation
      of Nrf2 and the transcriptional activation of the genes downstream of Nrf2.
      Overall, these findings suggest that an augmentation in GSK-3beta/Fyn signaling
      during diabetes contributes to a deficit in both the cellular redox state and the
      Nrf2-based adaptive response to OS. Moreover, they may also offer a new
      perspective in the understanding and treatment of nonhealing diabetic wounds.

PMID- 21878665
TI  - beta1-Adrenergic receptors increase UCP1 in human MADS brown adipocytes and
      rescue cold-acclimated beta3-adrenergic receptor-knockout mice via nonshivering
      thermogenesis.
AB  - With the finding that brown adipose tissue is present and negatively correlated
      to obesity in adult man, finding the mechanism(s) of how to activate brown
      adipose tissue in humans could be important in combating obesity, type 2
      diabetes, and their complications. In mice, the main regulator of nonshivering
      thermogenesis in brown adipose tissue is norepinephrine acting predominantly via
      beta(3)-adrenergic receptors. However, vast majorities of beta(3)-adrenergic
      agonists have so far not been able to stimulate human beta(3)-adrenergic
      receptors or brown adipose tissue activity, and it was postulated that human
      brown adipose tissue could be regulated instead by beta(1)-adrenergic receptors.
      Therefore, we have investigated the signaling pathways, specifically pathways to
      nonshivering thermogenesis, in mice lacking beta(3)-adrenergic receptors. Wild
      type and beta(3)-knockout mice were either exposed to acute cold (up to 12 h) or
      acclimated for 7 wk to cold, and parameters related to metabolism and brown
      adipose tissue function were investigated. beta(3)-knockout mice were able to
      survive both acute and prolonged cold exposure due to activation of beta(1)
      adrenergic receptors. Thus, in the absence of beta(3)-adrenergic receptors,
      beta(1)-adrenergic receptors are effectively able to signal via cAMP to elicit
      cAMP-mediated responses and to recruit and activate brown adipose tissue. In
      addition, we found that in human multipotent adipose-derived stem cells
      differentiated into functional brown adipocytes, activation of either beta(1)
      adrenergic receptors or beta(3)-adrenergic receptors was able to increase UCP1
      mRNA and protein levels. Thus, in humans, beta(1)-adrenergic receptors could play
      an important role in regulating nonshivering thermogenesis.

PMID- 21878666
TI  - Quality-of-life implications of immediate surgery and watchful waiting in
      asymptomatic aortic stenosis: a decision-analytic model.
AB  - BACKGROUND- Traditional management of severe aortic stenosis (AS) is based on
      delay in aortic valve replacement (AVR) until the development of symptoms.
      Surgery for asymptomatic AS has been proposed to reduce the small risk of sudden
      death before AVR and avoid heart failure (HF) after AVR. Because a trial to
      compare these options is unlikely, we developed a Markov model to inform the
      choice between immediate surgery and watchful waiting in asymptomatic AS. METHODS
      AND RESULTS- We defined health states as preoperative, postoperative,
      postcomplication, and death. We calculated the implications of watchful waiting,
      tissue and mechanical AVR-based on risks, transitions, utilities, and cost
      derived from literature review. Further analyses evaluated situations thought to
      favor immediate surgery and watchful waiting. Sensitivity analyses were based on
      the likelihood of preoperative death and HF in follow-up. In the reference case
      (age, 65 years; post-AVR utility, 0.9; annualized pre-AVR mortality, 1%; and post
      AVR HF, 11.3%), the utility of watchful waiting was superior to that of immediate
      mechanical or tissue AVR (quality-adjusted life-years, 7.4 versus 5.3 versus 5.3,
      respectively), and the cost was less than immediate surgery. Sensitivity analyses
      showed immediate surgery was not likely to be more effective regardless of the
      yearly probability of post-AVR HF in the watchful waiting group (range, 0% to
      80%). Immediate surgery was likely to be effective when pre-AVR annual mortality
      reached 13%. CONCLUSIONS- Immediate surgery in asymptomatic severe AS does not
      improve outcomes unless risk of sudden death pre-AVR and HF after AVR are higher
      than currently reported.

PMID- 21878667
TI  - Influence of age on perioperative complications among patients undergoing
      implantable cardioverter-defibrillators for primary prevention in the United
      States.
AB  - BACKGROUND- The majority of current implantable cardioverter-defibrillator (ICD)
      recipients are significantly older than those in the ICD trials. Data on
      periprocedural complications among the elderly are insufficient. We evaluated the
      influence of age on perioperative complications among primary prevention ICD
      recipients in the United States. METHODS AND RESULTS- Using the National
      Cardiovascular Data's ICD Registry, we identified 150 264 primary prevention
      patients who received ICDs from January 2006 to December 2008. The primary end
      point was any adverse event or in-hospital mortality. Secondary end points
      included major adverse events, minor adverse events, and length of stay. Of 150
      264 patients, 61% (n=91 863) were 65 years and older. A higher proportion of
      patients >=65 years had diabetes, congestive heart failure, atrial fibrillation,
      renal disease, and coronary artery disease. Approximately 3.4% of the entire
      cohort had any complication, including death, after ICD implant. Any adverse
      event or death occurred in 2.8% of patients under 65 years old; 3.1% of 65- to 69
      year-olds; 3.5% of 70- to 74-year-olds; 3.9% of 75- to 79-year-olds, 4.5% of 80-
      to 84-year-olds; and 4.5% of patients 85 years and older. After adjustment for
      clinical covariates, multivariate analysis found an increased odds of any adverse
      event or death among 75- to 79-year-olds (1.14 [95% confidence interval, 1.03 to
      1.25], 80-to 84-year-olds (1.22 [95% confidence interval, 1.10 to 1.36], and
      patients 85 years and older (1.15 [95% confidence interval, 1.01 to 1.32],
      compared with patients under 65 years old. CONCLUSIONS- Older patients had a
      modestly increased-but acceptably safe-risk of periprocedural complications and
      in-hospital mortality, driven mostly by increased comorbidity.

PMID- 21878668
TI  - Lost in translation: health resource variability in the achievement of optimal
      performance and clinical outcome.
AB  - BACKGROUND- An evidence-practice gap in acute coronary syndromes (ACS) is
      commonly recognized. System, provider, and patient factors can influence
      guideline adherence. Through using guideline facilitators in the clinical
      setting, the uptake of evidence-based recommendations may be increased. We
      hypothesized that facilitators of guideline recommendations (systems, tools, and
      workforce) in acute cardiac care were associated with increased guideline
      adherence and decreased adverse outcome. METHODS AND RESULTS- A cross-sectional
      evaluation of guideline facilitators was conducted in Australian hospitals. The
      population was derived from the Acute Coronary Syndrome Prospective Audit
      (ACACIA) and assessed performance, death, and recurrent myocardial infarction
      (death/re-MI) at 30 days and 12 months. Thirty-five hospitals and 2392 patients
      participated. Significant associations with decreased death/re-MI were observed
      with hospital strategies to facilitate primary percutaneous coronary intervention
      for ST-elevation MI patients (38/428 [8.9%] versus 30/154 [19.5%], P<0.001) and
      after adjustment (odds ratio [OR], 0.47 [95% confidence interval (CI), 0.24 to
      0.90], P<0.023), electronic discharge checklists (none: 233/1956 [11.9%],
      integrated; 43/251[17.1%], P=0.069, electronic; 6/124 [4.8%], P<0.001) and after
      adjustment (integrated versus none: OR, 1.66 [95% CI, 0.98 to 2.80], P=0.057 and
      electronic versus none: OR, 0.49 [95% CI, 0.35 to 0.68], P<0.001), and intensive
      cardiac care unit (ICCU) staff-to-patient ratios (neither: 200/1257 (15.9%), CCU:
      135/1051 (12.8%), ICCU: 8/84 (9.5%), P=0.049 and after adjustment (CCU versus
      neither: OR, 0.74 [95% CI, 0.47 to 1.14], P=0.172 and ICCU versus neither: OR,
      0.55; [95% CI, 0.38 to 0.81] P=0.003). CONCLUSIONS- Facilitating uptake of
      evidence in clinical practice may need to consider quality improvement systems,
      tools and workforce to achieve optimal ACS outcomes.

PMID- 21878669
TI  - Association of health professional shortage areas and cardiovascular risk factor
      prevalence, awareness, and control in the Multi-Ethnic Study of Atherosclerosis
      (MESA).
AB  - BACKGROUND- Individuals living in primary care health professional shortage areas
      (PC-HPSA), often have difficulty obtaining medical care; however, no previous
      studies have examined association of pc-hpsa residence with prevalence of
      cardiovascular disease risk factors. METHODS AND RESULTS- To examine this
      question, the authors used data from the Multi-Ethnic Study of Atherosclerosis
      baseline examination (2000-2002). Outcomes included the prevalence of diabetes,
      hypertension, hyperlipidemia, smoking, and obesity as well as the awareness and
      control of diabetes, hypertension, and hyperlipidemia. Multivariable Poisson
      models were used to examine the independent association of PC-HPSA residence with
      each outcome. Models were sequentially adjusted for demographics, acculturation,
      socioeconomic status, access to health care, and neighborhood socioeconomic
      status. Similar to the national average, 16.7% of Multi-Ethnic Study of
      Atherosclerosis participants lived in a PC-HPSA. In unadjusted analyses,
      prevalence rates of diabetes (14.8% versus 11.0%), hypertension (48.2% versus
      43.1%), obesity (35.7% versus 31.1%), and smoking (15.5% versus 12.1%) were
      significantly higher among residents of PC-HPSAs. There were no significant
      differences in the awareness or control of diabetes, hypertension, or
      hyperlipidemia. After adjustment, residence in a PC-HPSA was not independently
      associated with cardiovascular disease risk factor prevalence, awareness, or
      control. CONCLUSIONS- This study suggests that increased prevalence of
      cardiovascular disease risk factors in PC-HPSAs are explained by the demographic
      and socioeconomic characteristics of their residents. Future interventions aimed
      at increasing the number of primary care physicians may not improve
      cardiovascular risk without first addressing other factors underlying health care
      disparities.

PMID- 21878670
TI  - Influence of frailty and health status on outcomes in patients with coronary
      disease undergoing percutaneous revascularization.
AB  - BACKGROUND- Although older patients frequently undergo percutaneous coronary
      interventions (PCI), frailty, comorbidity, and quality of life are seldom part of
      risk prediction approaches. We assessed their incremental prognostic value over
      and above the risk factors in the Mayo Clinic risk score. METHODS AND RESULTS-
      Patients >=65 years who underwent PCI were assessed for frailty (Fried criteria),
      comorbidity (Charlson index), and quality of life [SF-36]. Of the 628 discharged
      [median follow-up of 35.0 months (interquartile range, 22.7 to 42.9)], 78 died
      and 72 had a myocardial infarction (MI). Three-year mortality was 28% for frail
      patients, 6% for nonfrail patients. The respective 3-year rates of death or MI
      were 41% and 17%. After adjustment, frailty [hazard ratio (HR), 4.19 [95%
      confidence interval (CI), 1.85, 9.51], physical component score of the SF-36 (HR,
      1.59; 95% CI, 1.24 to 2.02), and comorbidity, (HR, 1.10; 95% CI, 1.05, 1.16) were
      associated with mortality. Frailty was associated with mortality/MI (HR, 2.61,
      1.52, 4.50). Models with conventional Mayo Clinic risk score had C-statistics of
      0.628, 0.573 for mortality and mortality/MI, respectively. Adding frailty,
      quality of life, and comorbidity, the C-statistic was (0.675, 0.694, 0.671) for
      mortality and (0.607, 0.587, 0.576) for mortality/MI, respectively. Including
      frailty, comorbidities and SF-36, conferred a discernible improvement to predict
      death and death/MI (integrated discrimination improvement, 0.027 and 0.016, and
      net reclassification improvement of 43% and 18%, respectively). CONCLUSIONS-
      After PCI, frailty, comorbidity and poor quality of life are prevalent and are
      associated with adverse long-term outcomes. Their inclusion improves the
      discriminatory ability of the Mayo Clinic risk score derived from the routine
      cardiovascular risk factors.

PMID- 21878671
TI  - Risk factors associated with increased nonrelapse mortality and with poor overall
      survival in children with chronic graft-versus-host disease.
AB  - There is a paucity of information regarding the factors that affect nonrelapse
      mortality (NRM) and overall survival among children that develop chronic graft
      versus-host disease (cGVHD). We performed multivariate analyses using data from
      the Center for International Blood and Marrow Transplant Research to identify
      risk factors for NRM and survival in 1117 pediatric subjects with leukemia or
      myelodysplastic syndrome, transplanted from related donors, unrelated donors
      (URD), or unrelated cord blood between 1995 and 2004. We identified 4 variables
      associated with higher NRM: HLA partially matched or mismatched URD, peripheral
      blood cell graft, Karnofsky/Lansky score < 80 at cGVHD diagnosis, and platelets <
      100 * 10(9)/L at cGVHD diagnosis. Factors associated with significantly worse
      survival were: age > 10 years, transplantation from HLA partially matched or
      mismatched URD, advanced disease at transplantation, Karnofsky/Lansky < 80; and
      platelets < 100 * 10(9)/L. Cumulative incidence of discontinuation of systemic
      immune suppression at 1, 3, and 5 years after diagnosis of cGVHD were 22% (20%
      25%), 34% (31%-37%), and 37% (34%-40%), respectively. This is the largest study
      elucidating variables affecting outcome after diagnosis of cGVHD in pediatric
      allograft recipients. These variables may be useful for risk stratification,
      development of future clinical trials, and family counseling in children with
      cGVHD.

PMID- 21878672
TI  - Subtle differences in CTL cytotoxicity determine susceptibility to hemophagocytic
      lymphohistiocytosis in mice and humans with Chediak-Higashi syndrome.
AB  - Perforin-mediated cytotoxicity is important for controlling viral infections, but
      also for limiting immune reactions. Failure of this cytotoxic pathway leads to
      hemophagocytic lymphohistiocytosis (HLH), a life-threatening disorder of
      uncontrolled T-cell and macrophage activation. We studied susceptibility to HLH
      in 2 mouse strains (souris and beige(J)) and a cohort of patients with partial
      defects in perforin secretion resulting from different mutations in the LYST
      gene. Although both strains lacked NK-cell cytotoxicity, only souris mice
      developed all clinical and histopathologic signs of HLH after infection with
      lymphocytic choriomeningitis virus. The 2 strains showed subtle differences in
      CTL cytotoxicity in vitro that had a large impact on virus control in vivo.
      Whereas beige(J) CTLs eliminated lymphocytic choriomeningitis virus infection,
      souris CTLs failed to control the virus, which was associated with the
      development of HLH. In LYST-mutant patients with Chediak-Higashi syndrome, CTL
      cytotoxicity was reduced in patients with early-onset HLH, whereas it was
      retained in patients who later or never developed HLH. Thus, the risk of HLH
      development is set by a threshold that is determined by subtle differences in CTL
      cytotoxicity. Differences in the cytotoxic capacity of CTLs may be predictive for
      the risk of Chediak-Higashi syndrome patients to develop HLH.

PMID- 21878673
TI  - The cooperating mutation or "second hit" determines the immunologic visibility
      toward MYC-induced murine lymphomas.
AB  - In EMU-myc transgenic animals lymphoma formation requires additional genetic
      alterations, which frequently comprise loss of p53 or overexpression of BCL-2. We
      describe that the nature of the "second hit" affects the ability of the immune
      system to contain lymphoma development. Tumors with disrupted p53 signaling
      killed the host more rapidly than BCL-2 overexpressing ones. Relaxing immunologic
      control, using Tyk2(-/-) mice or by Ab-mediated depletion of CD8(+) T or natural
      killer (NK) cells accelerated formation of BCL-2-overexpressing lymphomas but not
      of those lacking p53. Most strikingly, enforced expression of BCL-2 prolonged
      disease latency in the absence of p53, whereas blocking p53 function in BCL-2
      overexpressing tumors failed to accelerate disease. This shows that blocking
      apoptosis in p53-deficient cells by enforcing BCL-2 expression can mitigate
      disease progression increasing the "immunologic visibility." In vitro
      cytotoxicity assays confirmed that high expression of BCL-2 protein facilitates
      NK and T cell-mediated killing. Moreover, we found that high BCL-2 expression is
      accompanied by significantly increased levels of the NKG2D ligand MULT1, which
      may account for the enhanced killing. Our findings provide first evidence that
      the nature of the second hit affects tumor immunosurveillance in c-MYC-driven
      lymphomas and define a potential shortcoming of antitumor therapies targeting BCL
      2.

PMID- 21878674
TI  - Sox4 cooperates with PU.1 haploinsufficiency in murine myeloid leukemia.
AB  - Cooperation of multiple mutations is thought to be required for cancer
      development. In previous studies, murine myeloid leukemias induced by transducing
      wild-type bone marrow progenitors with a SRY sex determining region Y-box 4
      (Sox4)-expressing retrovirus frequently carried proviral insertions at Sfpi1,
      decreasing its mRNA levels, suggesting that reduced Sfpi1 expression cooperates
      with Sox4 in myeloid leukemia induction. In support of this hypothesis, we show
      here that mice receiving Sox4 virus-infected Sfpi1(ko/+) bone marrow progenitors
      developed myeloid leukemia with increased penetrance and shortened latency.
      Interestingly, Sox4 expression further decreased Sfpi1 transcription. Ectopic
      SOX4 expression reduced endogenous PU.1 mRNA levels in HL60 promyelocytes, and
      decreased Sfpi1 mRNA levels were also observed in the spleens of leukemic and
      preleukemic mice receiving Sox4 virus-infected wild-type bone marrow cells. In
      addition, Sox4 protein bound to a critical upstream regulatory element of Sfpi1
      in ChIP assays. Such cooperation probably occurs in de novo human acute myeloid
      leukemias, as an analysis of 285 acute myeloid leukemia patient samples found a
      significant negative correlation between SOX4 and PU.1 expression. Our results
      establish a novel cooperation between Sox4 and reduced Sfpi1 expression in
      myeloid leukemia development and suggest that SOX4 could be an important new
      therapeutic target in human acute myeloid leukemia.

PMID- 21878676
TI  - Blood CD34-c-Kit+ cell rate correlates with aggressive forms of systemic
      mastocytosis and behaves like a mast cell precursor.
AB  - Mastocytosis is a heterogeneous disease characterized by the accumulation of mast
      cells in one or more organs. Our objective was to identify a peripheral mast cell
      precursor and assess its variation rate in mastocytosis. A peripheral blood
      phenotypic analysis was performed among 50 patients with mastocytosis who were
      enrolled in a prospective multicentric French study, and the phenotypic analysis
      results of the patients were compared with those of healthy donors. The rate of
      peripheral blood CD34(-)c-Kit(+) cells correlated with the severity of
      mastocytosis. This cellular population was isolated from healthy donors as well
      as from patients with systemic mastocytosis. After 30 days of culture, the CD34(
      )c-Kit(+) cells gave birth to mature mast cells, indicating that this cellular
      population constitutes a mast cell circulating precursor. Monitoring peripheral
      CD34(-)c-Kit(+) cells by flow cytometry could be a useful and low-invasive tool
      to determine the disease severity and the relapses and to assess treatment
      efficiency.

PMID- 21878675
TI  - The BCL11B tumor suppressor is mutated across the major molecular subtypes of T
      cell acute lymphoblastic leukemia.
AB  - The BCL11B transcription factor is required for normal T-cell development, and
      has recently been implicated in the pathogenesis of T-cell acute lymphoblastic
      leukemia (T-ALL) induced by TLX overexpression or Atm deficiency. To
      comprehensively assess the contribution of BCL11B inactivation to human T-ALL, we
      performed DNA copy number and sequencing analyses of T-ALL diagnostic specimens,
      revealing monoallelic BCL11B deletions or missense mutations in 9% (n = 10 of
      117) of cases. Structural homology modeling revealed that several of the BCL11B
      mutations disrupted the structure of zinc finger domains required for this
      transcription factor to bind DNA. BCL11B haploinsufficiency occurred across each
      of the major molecular subtypes of T-ALL, including early T-cell precursor, HOXA
      positive, LEF1-inactivated, and TAL1-positive subtypes, which have
      differentiation arrest at diverse stages of thymocyte development. Our findings
      provide compelling evidence that BCL11B is a haploinsufficient tumor suppressor
      that collaborates with all major T-ALL oncogenic lesions in human thymocyte
      transformation.

PMID- 21878678
TI  - Merlin/NF2 functions upstream of the nuclear E3 ubiquitin ligase CRL4DCAF1 to
      suppress oncogenic gene expression.
AB  - Integrin-mediated activation of PAK (p21-activated kinase) causes phosphorylation
      and inactivation of the FERM (4.1, ezrin, radixin, moesin) domain-containing
      protein Merlin, which is encoded by the NF2 (neurofibromatosis type 2) tumor
      suppressor gene. Conversely, cadherin engagement inactivates PAK, thus leading to
      accumulation of unphosphorylated Merlin. Current models imply that Merlin
      inhibits cell proliferation by inhibiting mitogenic signaling at or near the
      plasma membrane. We have recently shown that the unphosphorylated, growth
      inhibiting form of Merlin accumulates in the nucleus and binds to the E3
      ubiquitin ligase CRL4(DCAF1) to suppress its activity. Depletion of DCAF1 blocks
      the hyperproliferation caused by inactivation of Merlin. Conversely, expression
      of a Merlin-insensitive DCAF1 mutant counteracts the antimitogenic effect of
      Merlin. Expression of Merlin or silencing of DCAF1 in Nf2-deficient cells induce
      an overlapping, tumor-suppressive program of gene expression. Mutations present
      in some tumors from NF2 patients disrupt Merlin's ability to interact with or
      inhibit CRL4(DCAF1). Lastly, depletion of DCAF1 inhibits the hyperproliferation
      of Schwannoma cells isolated from NF2 patients and suppresses the oncogenic
      potential of Merlin-deficient tumor cell lines. Current studies are aimed at
      identifying the substrates and mechanism of action of CRL4(DCAF1) and examining
      its role in NF2-dependent tumorigenesis in mouse models. We propose that Merlin
      mediates contact inhibition and suppresses tumorigenesis by translocating to the
      nucleus to inhibit CRL4(DCAF1).

PMID- 21878677
TI  - Menopausal hormone therapy and risks of melanoma and nonmelanoma skin cancers:
      women's health initiative randomized trials.
AB  - BACKGROUND: Case-control studies have reported that exogenous estrogen use is
      associated with increased risk of skin cancer. The effects of menopausal hormone
      therapy on incidence of nonmelanoma skin cancer and melanoma were evaluated in
      post hoc analyses of the Women's Health Initiative randomized placebo-controlled
      hormone therapy trials of combined estrogen plus progestin (E + P) and estrogen
      only (E-alone). METHODS: Postmenopausal women aged 50-79 years were randomly
      assigned to conjugated equine estrogen (0.625 mg/d) plus medroxyprogesterone
      acetate (2.5 mg/d) or placebo in the E + P trial if they had an intact uterus (N
      = 16,608) or to conjugated equine estrogen alone or placebo in the E-alone trial
      if they had a hysterectomy (N = 10,739); the mean follow-up was 5.6 and 7.1
      years, respectively. Incident nonmelanoma skin cancers (n = 980 [E + P trial]; n
      = 820 [E-alone trial]) and melanomas (n = 57 [E + P trial]; n =38 [E-alone
      trial]) were ascertained by self-report. Incident cases of cutaneous malignant
      melanoma were confirmed by physician review of medical records. Incidences of
      nonmelanoma skin cancer and melanoma were compared between the two randomization
      groups within each trial using hazard ratios (HRs), with corresponding 95%
      confidence intervals (CIs) and Wald statistic P values from Cox proportional
      hazards models. All statistical tests were two-sided. RESULTS: Rates of incident
      nonmelanoma skin cancer and melanoma were similar between the active hormone
      (combined analysis of E + P and E-alone) and placebo groups (nonmelanoma skin
      cancer: HR = 0.98, 95% CI = 0.89 to 1.07; melanoma: HR = 0.92, 95% CI = 0.61 to
      1.37). Results were similar for the E + P and E-alone trials when analyzed
      individually. CONCLUSIONS: Menopausal hormone therapy did not affect overall
      incidence of nonmelanoma skin cancer or melanoma. These findings do not support a
      role of menopausal estrogen, with or without progestin, in the development of
      skin cancer in postmenopausal women.

PMID- 21878679
TI  - AKT promotes rRNA synthesis and cooperates with c-MYC to stimulate ribosome
      biogenesis in cancer.
AB  - Precise regulation of ribosome biogenesis is fundamental to maintain normal cell
      growth and proliferation, and accelerated ribosome biogenesis is associated with
      malignant transformation. Here, we show that the kinase AKT regulates ribosome
      biogenesis at multiple levels to promote ribosomal RNA (rRNA) synthesis.
      Transcription elongation by RNA polymerase I, which synthesizes rRNA, required
      continuous AKT-dependent signaling, an effect independent of AKT's role in
      activating the translation-promoting complex mTORC1 (mammalian target of
      rapamycin complex 1). Sustained inhibition of AKT and mTORC1 cooperated to reduce
      rRNA synthesis and ribosome biogenesis by additionally limiting RNA polymerase I
      loading and pre-rRNA processing. In the absence of growth factors, constitutively
      active AKT increased synthesis of rRNA, ribosome biogenesis, and cell growth.
      Furthermore, AKT cooperated with the transcription factor c-MYC to
      synergistically activate rRNA synthesis and ribosome biogenesis, defining a
      network involving AKT, mTORC1, and c-MYC as a master controller of cell growth.
      Maximal activation of c-MYC-dependent rRNA synthesis in lymphoma cells required
      AKT activity. Moreover, inhibition of AKT-dependent rRNA transcription was
      associated with increased lymphoma cell death by apoptosis. These data indicate
      that decreased ribosome biogenesis is likely to be a fundamental component of the
      therapeutic response to AKT inhibitors in cancer.

PMID- 21878682
TI  - Outbreak of mortality in psittacine birds in a mixed-species aviary associated
      with Erysipelothrix rhusiopathiae infection.
AB  - Erysipelothrix rhusiopathiae septicemia, associated with an increased mortality
      of captive psittacines in a mixed-species aviary, was diagnosed by
      histopathology, Gram staining, bacterial culture and sequencing,
      immunohistochemistry, and real-time polymerase chain reaction (PCR). Over a
      period of 23 days with no premonitory signs, 2 rainbow lorikeets and an eclectus
      parrot died. Of these birds, one lorikeet and the eclectus were submitted for
      necropsy. The main pathologic findings were thrombosis (2/2), bacterial
      embolism/thromboembolism (2/2), necrotizing hepatitis (2/2), necrohemorrhagic
      myocarditis (1/2), fibrinohemorrhagic and heterophilic visceral coelomitis (1/2),
      submandibular necrosuppurative dermatitis with necrotizing vasculitis and
      bacterial and fungal thromboembolism (1/2), and locally extensive
      rhabdomyonecrosis with bacterial embolism (1/2). Intralesional bacteria were
      positive by Gram staining and immunohistochemistry in both cases. E.
      rhusiopathiae was isolated by routine bacterial culture from the liver of the
      lorikeet, which was also positive by real-time PCR. This report is one of the
      rare descriptions of erysipelas in psittacines, and to the authors' knowledge, it
      appears to be the first in the described species using immunohistochemistry and
      real-time PCR on avian paraffin-embedded tissues for the diagnosis.

PMID- 21878681
TI  - Nasal tumor with widespread cutaneous metastases in a Golden Retriever.
AB  - An intact, 8-year-old, male Golden Retriever dog was presented for evaluation of
      a nasal mass and approximately 30 firm, raised, variably ulcerated dermal and
      subcutaneous masses. Histopathology of both nasal and multiple skin masses
      revealed multiple nonencapsulated, infiltrative masses comprising clusters,
      anastomosing trabeculae, and packets of neoplastic, round to ovoid,
      hyperchromatic cells with marked nuclear molding. Surrounding the neoplastic
      cells was a marked stromal response in which many of the spindle-shaped cells
      expressed muscle-specific actin and had ultrastructural features consistent with
      myofibroblasts. A literature search indicates that this is the first report in a
      peer-reviewed journal of cutaneous metastasis of a nasal neuroendocrine tumor in
      any domestic animal species.

PMID- 21878683
TI  - Diversification of genes for carotenoid biosynthesis in aphids following an
      ancient transfer from a fungus.
AB  - The pea aphid genome was recently found to harbor genes for carotenoid
      biosynthesis, reflecting an ancestral transfer from a fungus. To explore the
      evolution of the carotene desaturase gene family within aphids, sequences were
      retrieved from a set of 34 aphid species representing numerous deeply diverging
      lineages of aphids and analyzed together with fungal sequences retrieved from
      databases. All aphids have at least one copy of this gene and some aphid species
      have up to seven, whereas fungal genomes consistently have a single copy. The
      closest relatives of aphids, adelgids, also have carotene desaturase; these
      sequences are most closely related to those from aphids, supporting a shared
      origin from a fungal to insect transfer predating the divergence of adelgids and
      aphids. Likewise, all aphids, and adelgids, have carotenoid profiles that are
      consistent with their biosynthesis using the acquired genes of fungal origin
      rather than derivation from food plants. The carotene desaturase was acquired
      from a fungal species outside of Ascomycota or Basidiomycota and closest to
      Mucoromycotina among sequences available in databases. In aphids, an ongoing
      pattern of gene duplication is indicated by the presence of both anciently and
      recently diverged paralogs within genomes and by the presence of a high frequency
      of pseudogenes that appear to be recently inactivated. Recombination among
      paralogs is evident, making analyses of patterns of selection difficult, but
      tests of selection for a nonrecombining region indicates that duplications tend
      to be followed by bouts of positive selection. Species of Macrosiphini, which
      often show color polymorphisms, typically have a larger number of desaturase
      copies relative to other species sampled in the study. These results indicate
      that aphid evolution has been accompanied by ongoing evolution of carotenogenic
      genes, which have undergone duplication, recombination, and occasional positive
      selection to yield a wide variety of carotenoid profiles in different aphid
      species.

PMID- 21878680
TI  - Inositol pyrophosphates as mammalian cell signals.
AB  - Inositol pyrophosphates are highly energetic inositol polyphosphate molecules
      present in organisms from slime molds and yeast to mammals. Distinct classes of
      enzymes generate different forms of inositol pyrophosphates. The biosynthesis of
      these substances principally involves phosphorylation of inositol
      hexakisphosphate (IP6) to generate the pyrophosphate IP7. Initial insights into
      functions of these substances derived primarily from yeast, which contain a
      single isoform of IP6 kinase (yIP6K), as well as from the slime mold
      Dictyostelium. Mammalian functions for inositol pyrophosphates have been
      investigated by using cell lines to establish roles in various processes,
      including insulin secretion and apoptosis. More recently, mice with targeted
      deletion of IP6K isoforms as well as the related inositol polyphosphate
      multikinase (IPMK) have substantially enhanced our understanding of inositol
      polyphosphate physiology. Phenotypic alterations in mice lacking inositol
      hexakisphosphate kinase 1 (IP6K1) reveal signaling roles for these molecules in
      insulin homeostasis, obesity, and immunological functions. Inositol
      pyrophosphates regulate these processes at least in part by inhibiting activation
      of the serine-threonine kinase Akt. Similar studies of IP6K2 establish this
      enzyme as a cell death inducer acting by stimulating the proapoptotic protein
      p53. IPMK is responsible for generating the inositol phosphate IP5 but also has
      phosphatidylinositol 3-kinase activity--that participates in activation of Akt.
      Here, we discuss recent advances in understanding the physiological functions of
      the inositol pyrophosphates based in substantial part on studies in mice with
      deletion of IP6K isoforms. These findings highlight the interplay of IPMK and
      IP6K in regulating growth factor and nutrient-mediated cell signaling.

PMID- 21878685
TI  - The genomic signature of splicing-coupled selection differs between long and
      short introns.
AB  - Understanding the function of noncoding regions in the genome, such as introns,
      is of central importance to evolutionary biology. One approach is to assay for
      the targets of natural selection. On one hand, the sequence of introns,
      especially short introns, appears to evolve in an almost neutral manner. Whereas
      on the other hand, a large proportion of intronic sequence is under selective
      constraint. This discrepancy is largely dependent on intron length and
      differences in the methods used to infer selection. We have used a method based
      on DNA strand asymmetery that does not require comparison with any putatively
      neutrally evolving sequence, nor sequence conservation between species, to detect
      selection within introns. The strongest signal we identify is associated with
      short introns. This signal comes from a family of motifs that could act as
      cryptic 5' splice sites during mRNA processing, suggesting a mechanistic
      justification underlying this signal of selection. Together with an analysis of
      intron length and splice site strength, we observe that the genomic signature of
      splicing-coupled selection differs between long and short introns.

PMID- 21878684
TI  - Species-specific features of DARC, the primate receptor for Plasmodium vivax and
      Plasmodium knowlesi.
AB  - The DARC (Duffy antigen/receptor for chemokines) gene, also called Duffy or FY,
      encodes a membrane-bound chemokine receptor. Two malaria parasites, Plasmodium
      vivax and Plasmodium knowlesi, use DARC to trigger internalization into red blood
      cells. Although much has been reported on the evolution of DARC null alleles,
      little is known about the evolution of the coding portion of this gene or the
      role that protein sequence divergence in this receptor may play in disease
      susceptibility or zoonosis. Here, we show that the Plasmodium interaction domain
      of DARC is nearly invariant in the human population, suggesting that coding
      polymorphism there is unlikely to play a role in differential susceptibility to
      infection. However, an analysis of DARC orthologs from 35 simian primate species
      reveals high levels of sequence divergence in the Plasmodium interaction domain.
      Signatures of positive selection in this domain indicate that species-specific
      mutations in the protein sequence of DARC could serve as barriers to the
      transmission of Plasmodium between primate species.

PMID- 21878686
TI  - A simple method of staging AKI in children.

PMID- 21878687
TI  - Motor control strategies in a continuous task space.
AB  - Previous studies on sequential effects of human grasping behavior were restricted
      to binary grasp type selection. We asked whether two established motor control
      strategies, the end-state comfort effect and the hysteresis effect, would hold
      for sequential motor tasks with continuous solutions. To this end, participants
      were tested in a sequential (predictable) and a randomized (nonpredictable)
      perceptual-motor task, which offered a continuous range of posture solutions for
      each movement trial. Both the end-state comfort effect and the hysteresis effect
      were reproduced under predictable, continuous conditions, but only the end-state
      comfort effect was present under nonpredictable conditions. Experimental results
      further revealed a work range restriction effect, which was reproduced for the
      dominant and the nondominant hand.

PMID- 21878688
TI  - Exploring the merits of perceptual anticipation in the soccer penalty kick.
AB  - This study investigated whether soccer penalty-takers can exploit predictive
      information from the goalkeeper's actions. Eight low- and seven high-skilled
      participants kicked balls in a penalty task with the goalkeeper's action
      displayed on a large screen. The goalkeeper initiated his dive either before, at
      or after the ball was struck. The percentage of balls shot to the empty half of
      the goal was not above chance when the participants could only rely on predictive
      information. Gaze patterns suggested that the need to fixate the target location
      to maintain aiming accuracy hindered perceptual anticipation. It is argued that
      penalty-takers should select a target location in advance of the run-up to the
      ball and disregard the goalkeeper's actions.

PMID- 21878689
TI  - Parkinson's disease influences the structural variations present in the leg swing
      kinematics.
AB  - This study investigated the nature of the structural variations found in the
      motor output of individuals with Parkinson's disease (PD). Young (n = 21; 19.9 +/
      1.3 yrs.), aged (n = 9; 74.8 +/- 6.8 yrs.) and individuals with PD (n = 9; 73.4
      +/- 6.6 yrs.) swung their leg at a pendular frequency and frequencies that were
      20% faster and slower. This study had three key findings. First, individuals with
      PD have greater variability in the leg swing angular kinematics and swing times.
      These variations appear to be related to the 0-15 Hz band of the of angular
      displacement power spectrum. Second, changes in the structural variations appear
      to not be derived from a stochastic source. Third, the magnitude of the
      variations and the structure of the variations are influenced by the frequency
      that the leg is swung. These results are consistent with the viewpoint that
      changes in the magnitude of the variations and the regularity of the structural
      variations are dependent upon health and adaptability to the task dynamics.

PMID- 21878690
TI  - Articulatory kinematics in the dysarthria associated with Friedreich's ataxia.
AB  - Electromagnetic articulography (EMA) was used to investigate the tongue
      kinematics in the dysarthria associated with Friedreich's ataxia (FRDA). The
      subject group consisted of four individuals diagnosed with FRDA. Five
      nonneurologically impaired individuals, matched for age and gender, served as
      controls. Each participant was assessed using the AG-200 EMA system during six
      repetitions of the tongue tip sentence Tess told Dan to stay fit and the tongue
      back sentence Karl got a croaking frog. Results revealed reduced speed measures
      (i.e., maximum acceleration / deceleration / velocity), greater movement
      durations and increased articulatory distances for the approach phases of
      consonant productions. The approach phase, involving movement up to the palate,
      was more affected than the release phase. It is suggested that deviant lingual
      kinematics could be the outcome of disturbances to cerebellar function, or
      possibly in combination with disturbances to upper motor neuron systems.

PMID- 21878691
TI  - Stride interval dynamics are altered when two individuals walk side by side.
AB  - The purpose of this study was to examine the effects of interpersonal
      synchronization of stepping on stride interval dynamics during over-ground
      walking. Twenty-seven footswitch instrumented subjects walked under three
      conditions: independent (SOLO), alongside a partner (PAIRED), and side by side
      with intentional synchronization (FORCED). A subset of subjects also synchronized
      stepping to a metronome (MET). Stride time power spectral density and detrended
      fluctuation analysis revealed that the rate of autocorrelation decay in stride
      time was similar for both the SOLO and PAIRED conditions, but was significantly
      reduced during the FORCED and MET conditions (p=0.03 & 0.002). Stride time
      variability was also significantly increased for the FORCED and MET conditions
      (p<0.001). These data suggest that forced synchronization of stepping results in
      altered stride interval dynamics, likely through increased active control by the
      CNS. Passive side by side stepping, where synchronization is subconscious, does
      not appreciably alter stepping in this manner.

PMID- 21878692
TI  - Differences in descending control of external oblique and latissimus dorsi
      muscles in humans: a preliminary study.
AB  - Descending bilateral control of external oblique (EO) and latissimus dorsi (LD)
      was investigated using transcranial magnetic stimulation. Contralateral (CL)
      motor evoked potential (MEP) thresholds were lower and latencies were shorter
      than for ipsilateral (IL) MEPs. Hotspots for EO were symmetrical; this was not
      the case for LD. The volumes of drive to the left and right muscles were not
      different. The laterality index was not different between the left and right
      muscles. The average index for the EO muscles was closer to zero than that for
      LD, suggesting a stronger IL drive to EO. The symmetry of drive to each muscle
      did not differ; however, the symmetry of drive varies within a subject for
      different muscles and between subjects for the same muscle. The findings may be
      useful in understanding a number of clinical conditions relating to the trunk and
      also for predicting the outcome of rehabilitative strategies.

PMID- 21878693
TI  - Adaptive locomotion for crossing a moving obstacle.
AB  - Crossing moving obstacles requires different space-time adjustments compared with
      stationary obstacles. Our aim was to investigate gait spatial and temporal
      parameters in the approach and crossing phases of a moving obstacle. We
      hypothesized that obstacle speed affects gait parameters, which allow us to
      distinguish locomotor strategies. Ten young adults walked and stepped over an
      obstacle that crossed their way perpendicularly, under three obstacle conditions:
      control-stationary obstacle, slow (1.07m/s) and fast speed (1.71m/s) moving
      obstacles. Gait parameters were different between obstacle conditions, especially
      on the slow speed. In the fast condition, the participants adopted predictive
      strategies during the approach and crossing phases. In the slow condition, they
      used an anticipatory strategy in both phases. We conclude that obstacle speed
      affects the locomotor behavior and strategies were distinct in the obstacle
      avoidance phases.

PMID- 21878694
TI  - [Diagnostic imaging of cerebrovascular disease on multi-detector row computed
      tomography (MDCT)].
AB  - In this study, we reviewed characteristic diagnostic findings of vascular
      diseases in the central nervous system with 3-dimensional computed tomographic
      angiography (3D-CTA) using multi-detector row computed tomography (MDCT) and a
      novel 320-row area detector CT (320-ADCT). With coverage of 160 mm in a single
      rotation, 320-ADCT enables acquisition of both 4-dimensional CT angiography
      (dynamic 4D-CTA) and whole-brain CT perfusion imaging. We describe our experience
      of investigating cerebrovascular diseases with MDCT and 320-ADCT, as well as
      several postprocessing techniques to acquire images useful for diagnosis, therapy
      planning, and simulation of neurosurgical and endovascular intervention. 3D-CTA
      demonstrates has high accuracy in detecting and evaluating cerebral aneurysms and
      steno-occlusive diseases. Angiographic analysis, including information of
      surrounding tissues on 3D-CTA, allows assessment of the feasibility of
      neurosurgical or endovascular approaches and the technique to accomplish the
      therapy. However, 3D-CTA using MDCT is limited in its detection of aneurysms less
      than 3 mm in size and aneurysms embedded in the skull base region. In addition,
      discrimination between intradural paraclinoid aneurysms and extradural
      intracavernous aneurysms remains an unresolved problem in imaging of cerebral
      aneurysms. 320-ADCT may solve this problem with its high accuracy in
      discriminating arteries from the venous system. 3D-CTA could be used as an
      alternative to DSA for detection of severe carotid artery disease. 3D-CTA enables
      measurement of the lesions, plaque imaging, prediction of anatomical variants,
      screening for asymptomatic vascular lesions, and exclusion of patients with risk
      factors from carotid endoarterectomy (CEA) or carotid artery stenting (CAS). The
      diagnosis of intracranial dural arteriovenous fistula (DAVF) with CTA is
      challenging. Recently, several authors proposed diagnostic findings of ADVF by
      CTA and reported high sensitivity and specificity. 320-ADCT may offer
      comprehensive information for diagnosis and therapy planning of intracranial
      DAVF. Although DSA is a standard modality to detect spinal vascular
      malformations, selective catheterization requires considerable time and a certain
      amount of contrast medium, and is associated with a risk of neurological
      complications. Spinal 3D-CTA prior to DSA is useful in selective catheterization
      to arteries at certain spinal levels as well as when considering treatment
      options and therapy planning.

PMID- 21878695
TI  - [Utility and validity of SPECT and PET in the perioperative managements of
      patients with cervical internal carotid artery stenosis].
AB  - In this review, the author describes basic but essential knowledge on cerebral
      blood flow and metabolism in managing the patients with occlusive carotid artery
      diseases. Oxygen extraction fraction (OEF) and cerebrovascular reactivity to
      acetazolamide have widely been accepted as valuable parameters to identify the
      critical reduction of cerebral perfusion pressure in these patients. These
      parameters would play an important role in determining the candidates for
      extracranial-intracranial arterial bypass and in predicting their outcome.
      However, pathophysiology of cerebral ischemia in occlusive carotid artery
      diseases is not fully understood yet, and further studies would be warranted.
      Next, the author reviews previous reports on cerebral hemodynamics and metabolism
      in patients with severe stenosis of cervical internal carotid artery. Carotid
      endarterectomy (CEA) and carotid artery stenting (CAS) can dramatically improve
      cerebral hemodynamics, but may carry the risk to induce silent or symptomatic
      hyperperfusion in a certain subgroup of patients. Single photon emission computed
      tomography (SPECT) and positron emission tomography (PET) may also be useful for
      identifying patients at higher risk for postoperative hyperperfusion.

PMID- 21878696
TI  - [Ischemic cortical neuronal damage and cognitive impairments in atherosclerotic
      occlusive disease of the major cerebral artery: a PET study].
AB  - In atherosclerotic internal carotid artery (ICA) or middle cerebral artery (MCA)
      disease, selective neuronal damage can be detected as a decrease in central
      benzodiazepine receptors (BZRs) in an apparently normal cerebral cortex. To
      investigate the association between cortical BZRs decreases and executive
      dysfunctions, we measured BZRs using positron emission tomography (PET) and (11)C
      flumazenil in 60 non-disabled patients with unilateral atherosclerotic ICA or MCA
      disease and no cortical infarction. Using 3-dimensional stereotactic surface
      projections, we calculated the BZR index, a measure of abnormally decreased BZRs
      in the cerebral cortex within the anterior cerebral artery (ACA) or MCA
      territory, and found that it to be correlated with the patient's score on the
      Wisconsin Card Sorting Test (WCST). Based on the WCST results, 39 patients were
      considered abnormal (low categories achieved) for their age. The BZR index of the
      ACA territory in the hemisphere affected by arterial disease was significantly
      higher in abnormal patients than in normal patients. The BZR index of the MCA
      territory differed significantly between the 2 groups when patients with left
      arterial disease (n = 28) were analyzed separately. The BZR indices of the
      anterior cingulate gyrus and the middle frontal gyrus carrelated significantly
      and positively with the total number of WCST errors. In atherosclerotic ICA or
      MCA disease, selective neuronal damage that is manifested as a decrease in BZRs
      in the non-infarcted cerebral cortex is associated with executive dysfunction.
      PET imaging of BZRs is useful as an objective measure of cognitive impairments in
      atherosclerotic occlusive disease of the major cerebral artery.

PMID- 21878697
TI  - [Progress in NIRS monitoring of cerebral blood flow].
AB  - Various studies have demonstrated the usefulness of near infrared spectroscopy
      (NIRS) for detecting cerebral ischemia during a carotid endarterectomy; however,
      it is difficult to apply NIRS to the diagnosis of ischemic stroke, since
      commercially available NIRS, which uses continuous-wave light, does not provide
      quantitative values of baseline hemoglobin (Hb) concentrations. In contrast, time
      resolved near-infrared spectroscopy (TRS) permits quantitative measurement of Hb
      concentrations. We applied TRS to detection of cerebra vasospasm after
      subarachnoid hemorrhage (SAH). We investigated 11 age-matched controls and 14
      aneurysmal SAH patients that comprised 10 patients with World Federation of
      Neurological Societies (WFNS) grade V and 4 patients with WFNS grade II.
      Employing TR-NIRS, we measured the cortical oxygen saturation (CoSO2) and
      baseline Hb concentrations in the middle cerebral artery territory. The CoSO2 and
      Hb concentrations remained stable after SAH in 6 patients; digital subtraction
      angiography (DSA) did not reveal vasospasm in these patients. In 8 patients,
      however, CoSO2 and total Hb decreased abruptly between 5 and 9 days after SAH.
      DSA revealed diffuse vasospasms in 6 of 8 patients. The reduction of CoSO2
      predicted occurrence of vasospasm at a cutoff value of 3.9%-6.4% with 100%
      sensitivity and 85.7% specificity. Trans cranial Doppler (TCD) failed to detect
      vasospasm in 4 cases, whereas TR-NIRS could. Finally, TRS performed on day 1
      after SAH revealed significantly higher CoSO2 than that of the controls (p =
      0.048), but there was no significant difference in total Hb. TRS detected
      vasospasm by evaluating the CBO in the cortex and may be more sensitive than TCD,
      which assesses the blood flow velocity in the M1 portion. TRS may be useful for
      the diagnosis of ischemic events in stroke patients.

PMID- 21878698
TI  - [Plaque imaging of carotid stenosis: an update and future perspective].
AB  - Not only is the degree of stenosis important for optimal treatment of carotid
      stenosis, plaque characteristics, are also important factors to be considered.
      Various modalities of plaque imaging using ultrasound, magnetic resonance imaging
      (MRI), and positron emission tomography (PET) have been introduced to clinical
      practice recently. Here, we provide an overview of the recent progress of such
      modalities in relation to their clinical significance and future perspective.

PMID- 21878699
TI  - [Diagnosis of syringomyelia and its classification on the basis of symptoms,
      radiological appearance, and causative disorders].
AB  - Although it is easier to accurately diagnose syringomyelia with the advent of
      magnetic resonance (MR) imaging, syringomyelia still poses challenges to
      clinicians because of its complex symptomatology, uncertain pathogenesis and
      multiple treatment options. Here, we propose criteria for classification of
      syringomyelia not related to those associated with spinal intramedullary tumors.
      The classification aims to distinguish between the presyrinx state and
      syringomyelia, between asymptomatic and symptomatic syringomyelia and to clarify
      the associated disorders such as Chiari malformations, spinal arachnoiditis and
      spinal cord trauma. Diagnostic criteria for Chiari I and II malformations with MR
      imaging were also defined. Several hypotheses proposed to explain the
      pathogenesis of syringomyelia associated with Chiari I malformation were
      reviewed. A questionnaire survey on syringomyelia based on the proposed criteria
      conducted between November 2009 and April 2010 in Japan revealed that 160 (22.6%)
      of the 708 patients were asymptomatic. Chiari I malformation was the most
      frequent causative disorder (48.3%), followed by spinal arachnoiditis (15.8%).
      The proposed criteria for classification of syringomyelia will facilitate a
      nationwide survey of syringomyelia in Japan. Such a survey will inform us of its
      prevalence and prognosis more precisely, and enable us to build a reliable
      database that may help determine the optimal treatment for the disease in the
      future.

PMID- 21878700
TI  - [Food-borne botulism].
AB  - Botulism is a neuroparalytic disease caused by neurotoxins produced by
      Clostridium botulinum. Food-borne botulism is a kind of exotoxin-caused food
      intoxication. Although this disease is rarely reported in Japan now, it is a
      cause of great concern because of its high mortality rate, and botulism cases
      should be treated as a public health emergency. Botulism classically presents as
      acute symmetrical descending flaccid paralysis. Its diagnosis is based on the
      detection of botulinum toxins in the patient's serum or stool specimens.
      Electrophysiologic tests of such patients show reduced compound muscle action
      potentials (CMAPs), low amplitudes and short durations of motor unit potentials
      (MUPs), and mild waning in repetitive low-frequency stimulations. Single fiber
      electromyography (EMG) is particularly useful for the diagnosis of botulism. We
      report a case of food-borne botulism that we had encountered. An 83-year-old man
      with rapidly progressive diplopia, dysphagia, and tetraplegia was hospitalized;
      he required intensive care, including artificial ventilatory support.
      Electrophysiologic tests yielded findings compatible with botulism. We made a
      clinical diagnosis of food-borne botulism and administered antitoxin on the
      seventh disease day. The patient's motor symptoms started ameliorating several
      days after the antitoxin injection. Subsequently, botulinum toxin type A was
      detected in the patient's serum specimen by using a bioassay, and the type A gene
      and silent B gene were detected in his serum specimen by using polymerase chain
      reaction (PCR). C. botulinum was also obtained from stool culture on the 17th and
      50th disease days. Botulism is a curable disease if treated early. Although it is
      a rare condition, it should always be considered in the differential diagnosis of
      patients with rapid onset of cranial nerve and limb muscle palsies.

PMID- 21878701
TI  - [Mechanisms of intracerebral pain and itch perception in humans].
AB  - Electrophysiological studies involving techniques such as magnetoencephalography
      (MEG) and hemodynamic studies involving techniques such as functional magnetic
      resonance imaging (fMRI) have recently been intensively used to elucidate the
      mechanisms underlying pain and itch perception in humans. The MEG results
      obtained after A-delta fiber (first pain) and C fiber (second pain) stimulation
      were similar, except for longer latency in the case of C fibers. Initially, the
      primary somatosensory cortex (SI) contralateral to the stimulation is activated,
      and the secondary somatosensory cortex (SII), insula, amygdala, and anterior
      cingulate cortex (ACC) in both hemispheres are then activated sequentially. The
      fMRI findings obtained after the stimulation of C fibers and those obtained after
      the stimulation of A-delta fibers both showed activation of the bilateral
      thalamus, bilateral SII, right (ipsilateral) middle insula, and bilateral
      Brodmann's area (BA) 24/32, with most of the activity being detected in the
      posterior region of the ACC. However, the magnitude of activity in the anterior
      insula on both sides and in BA 32/8/6, including the ACC and pre-supplementary
      motor area (pre-SMA), after the stimulation of C nociceptors was significantly
      stronger than that after the stimulation of A-delta nociceptors. We have recently
      developed a new stimulation electrode that causes an itching sensation via
      electrical stimulation applied to skin. The conduction velocity (CV) of the
      signals caused by this stimulation is approximately 1 m/sec in a range of CV of C
      fibers. The findings obtained after itch stimulation were similar to those
      obtained after pain stimulation, but the precuneus may be an itch-selective brain
      region. This unique finding was confirmed by both MEG and fMRI studies.

PMID- 21878702
TI  - [in-hospital mortality in patient with acute ischemic and hemorrhagic stroke].
AB  - There is a lack of evidence to compare in-hospital mortality with different types
      of stroke. The purpose of this study was to elucidate the in-hospital mortality
      after acute ischemic/hemorrhagic stroke and compare the factors associated with
      the mortality among stroke subtypes. All patients admitted to Kurashiki Central
      Hospital in Japan between January 2009 and December 2009, and diagnosed with
      acute ischemic/hemorrhagic stroke were included in this study. Demographics and
      clinical data pertaining to the patients were obtained from their medical
      records. Out of 738 patients who had an acute stroke, 53 (7.2%) died in the
      hospital. The in-hospital mortality was significantly lower in the cerebral
      infarction group than in the intracerebral hemorrhage and subarachnoid hemorrhage
      group (3.5%, 15.1%, and 17.9%, respectively; P<0.0001). Age was significantly
      lower in the subarachnoid hemorrhage group than in the other 2 groups. With
      regard to past history, diabetes mellitus was significantly found to be a
      complication in mortality cases of intracranial hemorrhage. Further investigation
      is needed to clarify the effect of diabetes on mortality after intracranial
      hemorrhage.

PMID- 21878703
TI  - [An autopsy case of progressive multifocal leukoencephalopathy: comparison of
      magnetic resonance imaging findings with the pathological findings].
AB  - A 41-year-old man diagnosed with malignant lymphoma (MLy) in November 2007
      developed paralysis that worsened rapidly in January 2008. Magnetic resonance
      imaging (MRI) showed multifocal T2 high-intensity lesions without edema or
      gadolinium enhancement in the white matter. The lesions were characterized by a
      central core with low signal intensity, surrounded by a rim of high signal
      intensity on diffusion-weighted images (DWIs). At first, we suspected brain
      metastasis of MLy and used anti-cancer drugs, but the patient's condition
      worsened. A brain biopsy was then taken to determine whether the patient had MLy
      metastasis or progressive multifocal leukoencephalopathy (PML) so that an
      appropriate course of treatment could be determined. The biopsy contained no
      characteristic nuclear inclusions of PML, but we were able to rule out MLy;
      therefore, the patient was treated with cytarabine in February 2008, but he died
      because of sepsis in March. Upon autopsy, many characteristic nuclear inclusions
      of PML were found in the periphery of the lesions, and in the central core, there
      was severe demyelinating and tissue softening without typical nuclear inclusions
      of oligodendroglias. This structure is similar to the structure observed on DWIs,
      in which a low signal intensity core is surrounded by a rim of high signal
      intensity. The presence of inclusion bodies in the rim would correspond to the
      high signal intensity area on DWIs. The peripheral area may have given high
      signal intensity on DWIs because of the active findings of many swelling
      oligodendroglias with typical nuclear inclusions. Conversely, the central lesions
      would give low signals on DWIs because of demyelination and softening. Hence, the
      region with high signal intensity adjacent to the central low signal area on DWIs
      would be an appropriate biopsy point for PML diagnosis. ).

PMID- 21878704
TI  - [Trigeminal neuralgia in an elderly patient associated with a variant of
      persistent primitive trigeminal artery].
AB  - An 86-year-old woman presented with a 10-year history of right paroxysmal facial
      pain. The trigger zone was the right maxilla. Magnetic resonance (MR) angiography
      and MR cisternography sourse images showed an aberrant artery originating from
      the right internal carotid artery anastomosed to the anterior inferior cerebellar
      artery territory (AICA) of the cerebellum, and it was closed at the root entry
      zone of trigeminal nerve. The patient underwent microvascular decompression
      (MVD), and her pain resolved after the operation. Most of the offending vessels
      that cause trigeminal neuralgia are the superior cerebellar artery (75-80%) and
      AICA. Although persistent primitive trigeminal artery (PTA) is the most common
      type of persistent carotid-basilar anastomosis, trigeminal neuralgia associated
      with PTA or a PTA variant is very rare, and particularly, a PTA variant is an
      uncommon, anomalous, intracranial vessel. It is necessary to inspect MR imaging
      scans carefully prior to MVD surgery because they are frequently associated with
      intracranial aneurysms. During surgery, we must be careful not to injure the
      perforating arteries from the PTA variant. MVD for trigeminal neuralgia in
      elderly patients is effective if the patients can have a tolerate general
      anesthesia. However, when we plan surgery for elderly patients, we must take care
      that it does not to lead to unexpected complications.

PMID- 21878705
TI  - [Usefulness of contrast-enhanced fluid attenuated inversion recovery magnetic
      resonance imaging for diagnosing carcinomatous meningitis: a case report].

PMID- 21878706
TI  - Multielectrode array recordings of bladder and perineal primary afferent activity
      from the sacral dorsal root ganglia.
AB  - The development of bladder and bowel neuroprostheses may benefit from the use of
      sensory feedback. We evaluated the use of high-density penetrating microelectrode
      arrays in sacral dorsal root ganglia (DRG) for recording bladder and perineal
      afferent activity. Arrays were inserted in S1 and S2 DRG in three anesthetized
      cats. Neural signals were recorded while the bladder volume was modulated and
      mechanical stimuli were applied to the perineal region. In two experiments, 48
      units were observed that tracked bladder pressure with their firing rates (79%
      from S2). At least 50 additional units in each of the three experiments (274
      total; 60% from S2) had a significant change in their firing rates during one or
      more perineal stimulation trials. This study shows the feasibility of obtaining
      bladder-state information and other feedback signals from the pelvic region with
      a sacral DRG electrode interface located in a single level. This natural source
      of feedback would be valuable for providing closed-loop control of bladder or
      other pelvic neuroprostheses.

PMID- 21878707
TI  - First controlled vertical flight of a biologically inspired microrobot.
AB  - In this paper, we present experimental results on altitude control of a flying
      microrobot. The problem is approached in two stages. In the first stage, system
      identification of two relevant subsystems composing the microrobot is performed,
      using a static flapping experimental setup. In the second stage, the information
      gathered through the static flapping experiments is employed to design the
      controller used in vertical flight. The design of the proposed controller relies
      on the idea of treating an exciting signal as a subsystem of the microrobot. The
      methods and results presented here are a key step toward achieving total autonomy
      of bio-inspired flying microrobots.

PMID- 21878708
TI  - Percent voluntary inactivation and peak force predictions with the interpolated
      twitch technique in individuals with high ability of voluntary activation.
AB  - The purpose of this study was to examine the sensitivity and peak force
      prediction capability of the interpolated twitch technique (ITT) performed during
      submaximal and maximal voluntary contractions (MVCs) in subjects with the ability
      to maximally activate their plantar flexors. Twelve subjects performed two MVCs
      and nine submaximal contractions with the ITT method to calculate percent
      voluntary inactivation (%VI). Additionally, two MVCs were performed without the
      ITT. Polynomial models (linear, quadratic and cubic) were applied to the 10-90%
      VI and 40-90% VI versus force relationships to predict force. Peak force from the
      ITT MVC was 6.7% less than peak force from the MVC without the ITT. Fifty-eight
      percent of the 10-90% VI versus force relationships were best fit with nonlinear
      models; however, all 40-90% VI versus force relationships were best fit with
      linear models. Regardless of the polynomial model or the contraction intensities
      used to predict force, all models underestimated the actual force from 22% to
      28%. There was low sensitivity of the ITT method at high contraction intensities
      and the predicted force from polynomial models significantly underestimated the
      actual force. Caution is warranted when interpreting the % VI at high contraction
      intensities and predicted peak force from submaximal contractions.

PMID- 21878709
TI  - Unbinding of targeted ultrasound contrast agent microbubbles by secondary
      acoustic forces.
AB  - Targeted molecular imaging with ultrasound contrast agent microbubbles is
      achieved by incorporating targeting ligands on the bubble coating and allows for
      specific imaging of tissues affected by diseases. Improved understanding of the
      interplay between the acoustic forces acting on the bubbles during insonation
      with ultrasound and other forces (e.g. shear due to blood flow, binding of
      targeting ligands to receptors on cell membranes) can help improve the efficacy
      of this technique. This work focuses on the effects of the secondary acoustic
      radiation force, which causes bubbles to attract each other and may affect the
      adhesion of targeted bubbles. First, we examine the translational dynamics of
      ultrasound contrast agent microbubbles in contact with (but not adherent to) a
      semi-rigid membrane due to the secondary acoustic radiation force. An equation of
      motion that effectively accounts for the proximity of the membrane is developed,
      and the predictions of the model are compared with experimental data extracted
      from optical recordings at 15 million frames per second. A time-averaged model is
      also proposed and validated. In the second part of the paper, initial results on
      the translation due to the secondary acoustic radiation force of targeted,
      adherent bubbles are presented. Adherent bubbles are also found to move due to
      secondary acoustic radiation force, and a restoring force is observed that brings
      them back to their initial positions. For increasing magnitude of the secondary
      acoustic radiation force, a threshold is reached above which the adhesion of
      targeted microbubbles is disrupted. This points to the fact that secondary
      acoustic radiation forces can cause adherent bubbles to detach and alter the
      spatial distribution of targeted contrast agents bound to tissues during
      activation with ultrasound. While the details of the rupture of intermolecular
      bonds remain elusive, this work motivates the use of the secondary acoustic
      radiation force to measure the strength of adhesion of targeted microbubbles.

PMID- 21878710
TI  - Pre- and post-natal exposure of children to EMF generated by domestic induction
      cookers.
AB  - Induction cookers are a type of cooking appliance that uses an intermediate
      frequency magnetic field to heat the cooking vessel. The magnetic flux density
      produced by an induction cooker during operation was measured according to the EN
      62233 standard, and the measured values were below the limits set in the
      standard. The measurements were used to validate a numerical model consisting of
      three vertically displaced coaxial current loops at 35 kHz. The numerical model
      was then used to compute the electric field (E) and induced current (J) in 26 and
      30 weeks pregnant women and 6 and 11 year old children. Both E and J were found
      to be below the basic restrictions of the 2010 low-frequency and 1998 ICNRIP
      guidelines. The maximum computed E fields in the whole body were 0.11 and 0.66 V
      m(-1) in the 26 and 30 weeks pregnant women and 0.28 and 2.28 V m(-1) in the 6
      and 11 year old children (ICNIRP basic restriction 4.25 V m(-1)). The maximum
      computed J fields in the whole body were 46 and 42 mA m(-2) in the 26 and 30
      weeks pregnant women and 27 and 16 mA m(-2) in the 6 and 11 year old children
      (ICNIRP basic restriction 70 mA m(-2)).

PMID- 21878711
TI  - Doped graphene: the interplay between localization and frustration due to the
      underlying triangular symmetry.
AB  - An intuitive explanation of the increase in localization observed near the Dirac
      point in doped graphene is presented. To do this, we renormalize the tight
      binding Hamiltonians in such a way that the honeycomb lattice maps into a
      triangular one. Then, we investigate the frustration effects that emerge in this
      Hamiltonian. In this doped triangular lattice, the eigenstates have a bonding and
      antibonding contribution near the Dirac point, and thus there is a kind of
      Lifshitz tail. The increase in frustration is related to an increase in
      localization, since the number of frustrated bonds decreases with disorder, while
      the frustration contribution raises.

PMID- 21878712
TI  - Intramolecular vibrations and noise effects on pattern formation in a molecular
      helix.
AB  - Modulational instability in a biexciton molecular chain is addressed. We show
      that the model can be reduced to a set of three coupled equations: two nonlinear
      Schrodinger equations and a Boussinesq equation. The linear stability analysis of
      continuous wave solutions of the coupled systems is performed and the growth rate
      of instability is found numerically. Simulations of the full discrete systems
      reveal some behaviors of modulational instability, since wave patterns are
      observed for the excitons and the phonon spectrum. We also take the effect of
      thermal fluctuations into account and we numerically study both the stability and
      the instability of the plane waves under 300 K. The plane wave is found to be
      stable under modulation, but displays a gradual increase of the wave amplitudes.
      Under modulation, the same behaviors are observed and wave patterns are found to
      resist thermal fluctuations, which is in agreement with earlier research on
      localized structure stability under thermal noise.

PMID- 21878713
TI  - Tracer diffusion in fibre networks: the impact of spatial fluctuations in the
      fibre distribution.
AB  - A mean-field formalism that addresses spatial non-uniformities in fibre networks
      is combined with the cylindrical cell model to calculate the diffusion constant
      for a spherical tracer. Deviations from randomness in the fibre distribution are
      described by an operational distribution over volume fractions that is
      parametrized by mean values for the pore radii and void space chord lengths.
      Weight factors for elements with different radii in the cell model are assigned
      in a manner that enforces agreement with the distribution over pore sizes
      predicted by our treatment of heterogeneous networks. Illustrative calculations
      suggest that the tracer diffusion constant is quite sensitive to non-uniformities
      in the network, particularly for tracer particles with radii that are large
      compared to the fibre diameter.

PMID- 21878714
TI  - Static, dynamic and electronic properties of expanded fluid mercury in the metal
      nonmetal transition range. An ab initio study.
AB  - Fluid Hg undergoes a metal-nonmetal (M-NM) transition when expanded toward a
      density of around 9 g cm(-3). We have performed ab initio molecular dynamics
      simulations for several thermodynamic states around the M-NM transition range and
      the associated static, dynamic and electronic properties have been analyzed. The
      calculated static structure shows a good agreement with the available
      experimental data. It is found that the volume expansion decreases the number of
      nearest neighbors from 10 (near the triple point) to around 8 at the M-NM
      transition region. Moreover, these neighbors are arranged into two subshells and
      the decrease in the number of neighbors occurs in the inner subshell. The
      calculated dynamic structure factors agree fairly well with their experimental
      counterparts obtained by inelastic x-ray scattering experiments, which display
      inelastic side peaks. The derived dispersion relation exhibits some positive
      dispersion for all the states, although its value around the M-NM transition
      region is not as marked as suggested by the experiment. We have also calculated
      the electronic density of states, which shows the appearance of a gap at a
      density of around 8.3 g cm(-3).

PMID- 21878716
TI  - From stable divalent to valence-fluctuating behaviour in Eu(Rh(1-x)Ir(x))2Si2
      single crystals.
AB  - We have succeeded in growing high-quality single crystals of the valence
      fluctuating system EuIr(2)Si(2), the divalent Eu system EuRh(2)Si(2) and the
      substitutional alloy Eu(Rh(1-x)Ir(x))(2)Si(2) across the range 0 < x < 1, which
      we characterized by means of x-ray diffraction, energy-dispersive x-ray
      spectroscopy, specific heat, magnetization and resistivity measurements. On
      increasing x, the divalent Eu ground state subsists up to x = 0.25 with a slight
      increase in Neel temperature, while for 0.3<=x < 0.7 a sharp hysteretic change in
      susceptibility and resistivity marks the first-order valence transition. For
      x?0.7 the broad feature observed in the physical properties is characteristic of
      the continuous valence evolution beyond the critical end point of the valence
      transition line, and the resistivity is reminiscent of Kondo-like behaviour while
      the Sommerfeld coefficient indicates a mass renormalization of at least a factor
      of 8. The resulting phase diagram is similar to those reported for
      polycrystalline Eu(Pd(1-x)Au(x))(2)Si(2) and EuNi(2)(Si(1-x)Ge(x))(2), confirming
      its generic character for Eu systems, and markedly different to those of
      homologue Ce and Yb systems, which present a continuous suppression of the
      antiferromagnetism accompanied by a very smooth evolution of the valence. We
      discuss these differences and suggest them to be related to the large
      polarization energy of the Eu half-filled 4f shell. We further argue that the
      changes in the rare earth valence between RRh(2)Si(2) and RIr(2)Si(2) (R = Ce,
      Eu, Yb) are governed by a purely electronic effect and not by a volume effect.

PMID- 21878715
TI  - Signatures of spin-glass behaviour in PrIr2B2 and heavy fermion behaviour in
      PrIr2B2C.
AB  - The magnetic and transport properties of PrIr(2)B(2) and PrIr(2)B(2)C have been
      investigated by dc and ac magnetic susceptibility, specific heat, electrical
      resistivity and magnetoresistance measurements. PrIr(2)B(2) forms in CaRh(2)B(2)
      type orthorhombic crystal structure (space group Fddd). At low fields the dc
      magnetic susceptibility of PrIr(2)B(2) exhibits a sharp anomaly near 46 K which
      is followed by an abrupt increase below 10 K with a peak at 6 K, and split-up in
      ZFC and FC data below 46 K. In contrast, the specific heat exhibits only a broad
      Schottky type hump near 9 K which indicates that there is no long range magnetic
      order in this compound. The thermo-remanent magnetization is found to decay very
      slowly with a mean relaxation time tau = 3917 s. An ac magnetic susceptibility
      measurement also observes two sharp anomalies; the peak positions strongly depend
      on the frequency and shift towards high temperature with an increase in
      frequency, obeying the Vogel-Fulcher law as expected for a canonical spin-glass
      system. The two spin-glass transitions occur at freezing temperatures T(f1) = 36
      K and T(f2) = 3.5 K with shifts in the freezing temperatures per decade of
      frequency deltaT(f1) = 0.044 and deltaT(f2) = 0.09. An analysis of the frequency
      dependence of the transition temperature with critical slowing down,
      tau(max)/tau(0) = [(T(f)-T(SG))/T(SG)](-znu), gives tau(0) = 10(-7) s and
      exponent znu = 8, and the Vogel-Fulcher law gives an activation energy of 84 K
      for T(f1) and 27.5 K for T(f2). While znu = 8 is typical for spin-glass system,
      the characteristic relaxation time tau(0) = 10(-7) s is very large and comparable
      to that of superspin-glass systems. An addition of C in PrIr(2)B(2) leads to
      PrIr(2)B(2)C which forms in LuNi(2)B(2)C-type tetragonal structure (space group
      I4/mmm) and remains paramagnetic down to 2 K. The specific heat data show a broad
      Schottky type anomaly, which could be fairly reproduced with CEF analysis which
      suggests that the ground state is a CEF-split singlet and the first excited state
      singlet is situated 15 K above the ground state. The Sommerfeld coefficient
      gamma~300 mJ mol(-1) K(-2) of PrIr(2)B(2)C is very high and reflects a heavy
      fermion behaviour in this compound. We believe that the heavy fermion state in
      PrIr(2)B(2)C has its origin in low lying crystal field excitations as has been
      observed in PrRh(2)B(2)C.

PMID- 21878717
TI  - Determination of the equilibrium charge distribution for polyampholytes of
      different compactness in a single computer experiment.
AB  - The conformational properties of charge-balanced polyampholytes described by the
      end-to-end distance or radius of gyration depend on parameters such as the
      temperature and pH as well as on the detailed charge distribution along the
      backbone. In this work we present a method to determine the charge distribution
      along a semi-stiff polyampholyte backbone which will result in a
      thermodynamically stable structure for the compactness of interest, from several
      loops to an uncoiled structure, performed in a single computer experiment.

PMID- 21878718
TI  - Domain size and structure in exchange coupled [Co/Pt]/NiO/[Co/Pt] multilayers.
AB  - We investigate the competing effects of interlayer exchange coupling and
      magnetostatic coupling in the magnetic heterostructure ([Co/Pt]/NiO/[Co/Pt]) with
      perpendicular magnetic anisotropy (PMA). This particular heterostructure is
      unique among coupled materials with PMA in directly exhibiting both ferromagnetic
      and antiferromagnetic coupling, oscillating between the two as a function of
      spacer layer thickness. By systematically tuning the coupling interactions via a
      wedge-shaped NiO spacer layer, we explore the energetics that dictate magnetic
      domain formation using high resolution magnetic force microscopy coupled with the
      magneto-optical Kerr effect. This technique probes the microscopic and
      macroscopic magnetic behavior as a continuous function of thickness and the
      interlayer exchange coupling, including the regions where interlayer coupling
      goes through zero. We see significant changes in domain structure based on the
      sign of coupling, and also show that magnetic domain size is directly related to
      the magnitude of the interlayer exchange coupling energy, which generally
      dominates over the magnetostatic interactions. When magnetostatic interactions
      become comparable to the interlayer exchange coupling, a delicate interplay
      between the differing energy contributions is apparent and energy scales are
      extracted. The results are of intense interest to the magnetic recording industry
      and also illustrate a relatively new avenue of undiscovered physics, primarily
      dealing with the delicate balance of energies in the formation of magnetic
      domains for coupled systems with PMA, defining limits on domain size as well as
      the interplay between roughness, domains and magnetic coupling.

PMID- 21878719
TI  - Dynamic analysis of the photoenhancement process of colloidal quantum dots with
      different surface modifications.
AB  - Photoinduced fluorescence enhancement of colloidal quantum dots (QDs) is a hot
      topic addressed in many studies due to its great influence on the bioanalytical
      performance of such nanoparticles. However, understanding of this process is not
      a simple task, and it cannot be explained by a general mechanism as it greatly
      depends on the QDs' nature, solubilization strategies, surrounding environment,
      etc. In this vein, we have critically compared the behavior of CdSe QDs (widely
      used in bioanalytical applications) with different surface modifications (ligand
      exchange and polymer coating), in different controlled experimental conditions,
      in the presence-absence of the ZnS layer and in different media when exposed for
      long times to intense UV irradiation. Thus six different types of colloidal QDs
      were finally studied. This research was carried out from a novel perspective,
      based on the analysis of the dynamic behavior of the photoactivation process (of
      great interest for further applications of QDs as labels in biomedical
      applications). The results showed a different behavior of the studied colloidal
      QDs after UV irradiation in terms of their photoluminescence characteristics,
      potential toxicity due to metal release to the environment, nanoparticle
      stability and surface coating degradation.

PMID- 21878720
TI  - A graphene oxide-carbon nanotube grid for high-resolution transmission electron
      microscopy of nanomaterials.
AB  - A novel grid for use in transmission electron microscopy is developed. The
      supporting film of the grid is composed of thin graphene oxide films overlying a
      super-aligned carbon nanotube network. The composite film combines the advantages
      of graphene oxide and carbon nanotube networks and has the following properties:
      it is ultra-thin, it has a large flat and smooth effective supporting area with a
      homogeneous amorphous appearance, high stability, and good conductivity. The
      graphene oxide-carbon nanotube grid has a distinct advantage when characterizing
      the fine structure of a mass of nanomaterials over conventional amorphous carbon
      grids. Clear high-resolution transmission electron microscopy images of various
      nanomaterials are obtained easily using the new grids.

PMID- 21878721
TI  - Facile synthesis of gold nanoflowers with high surface-enhanced Raman scattering
      activity.
AB  - Highly branched gold nanoflowers are synthesized in high yield by a simple amino
      reducing method, without additional seeds or surfactant agents. We present a
      systematic investigation of the influence of different parameters on the size,
      morphology, and monodispersity of gold nanoflowers. The initial concentration of
      reducing agent, the solvent viscosity, and the reaction temperature play critical
      roles in the formation of nanoparticles. A lower concentration of reducing agent
      causes larger particles with sharp and dendritic tips. Moreover, with increasing
      solvent viscosity, the obtained particles have more and larger tips. Examination
      of the nanoparticles at different reaction stages with transmission electron
      microscopy and UV-vis spectroscopy reveals the formation of the gold nanoflowers
      as a classical growth process in which diffusion-controlled growth gives rise to
      the highly branched structures. Additionally, these gold nanoflowers have
      prospects for surface-enhanced Raman scattering (SERS) imaging because of their
      strong SERS enhancement and clean surface.

PMID- 21878722
TI  - [Lesion localization of non-aphasic alexia and agraphia].
AB  - The author reviews the lesion localization of non-aphasic alexia and agraphia and
      proposes a new classification of alexia and agraphia on this basis. The newly
      proposed alexia and agraphia are pure alexia for kana (Japanese phonograms), or
      more generally pure alexia for letters, caused by a lesion in the posterior
      occipital area (posterior fusiform/inferior occipital gyri), and pure agraphia
      for kanji (Japanese morphograms) caused by a lesion in the posterior middle
      temporal gyrus and also a lesion restricted to the angular gyrus. In addition,
      the anatomical lesions presumably responsible for the parietal apraxic agraphia,
      frontal pure agraphia and thalamic agraphia are discussed.

PMID- 21878723
TI  - [Standard treatment for late-onset myasthenia gravis in Japan].
AB  - Myasthenia gravis (MG) is caused by the failure of neuromuscular transmission
      mediated by autoantibodies against acetylcholine receptors (AChR) and muscle
      specific receptor tyrosine kinase (MuSK). These seropositivity rates in AChR
      positive and MuSK positive MG in Japan are 80-85% and 5-10%, respectively. The
      incidence of late-onset MG has been increasing all over the world. A nationwide
      epidemiological survey in Japan also revealed that the rates of late-onset MG
      (onset after 50 years) had increased from 20% in 1987 to 42% in 2006. In 2010, a
      guideline for standard treatments in late-onset MG was published from Japanese
      Scoiety of Neurological Therapeutics. Based on individual experiences and the
      limited evidence, epidemiological characteristics of MG onset age, clinical
      features, and the standard treatment for late-onset patients are included in it.
      In this guideline summary, the ocular form was more frequent in late-onset
      compared to early-onset group, the indication of thymectomy in late-onset MG is
      less than that of early-onset MG and the combination of corticosteroids and
      immunosuppressive agents are recommended in order to reduce doses of
      corticosteroids in late-onset MG.

PMID- 21878724
TI  - [An autopsied case of postinfectious neuromyelitis optica in an 84-year-old man].
AB  - An 84-year-old man presented with acute bilateral visual impairment 2 weeks after
      an upper respiratory tract infection. A few days later, he developed left
      hemiparesis, followed by paraplegia. The brain magnetic resonance imaging (MRI)
      showed high-intensity lesions in the right cerebellum, pons, left and right
      corona radiata, and right putamen. The diffusion weighted image also showed these
      high-intensity lesions. The spinal MRI showed an edematous, longitudinally
      extensive, cord lesion at the C5-Th6 level of the spine. Intravenous
      corticosteroid therapy was initiated, but the patient showed mild improvement.
      Although methylprednisolone pulse therapy was administered 5 times, he continued
      to present with clinical relapse and died on day 50. Anti-aquaporin-4 (AQP4)
      antibodies were detected in the patient's serum. Autopsy findings showed necrotic
      lesions at the spinal cord, brain, and optic chiasma and nerves. An
      immunohistopathological study showed the loss of AQP4- and glial fibrillary
      acidic protein (GFAP)-positive cells, with relatively preserved myelin basic
      protein (MBP)-positive myelin in the necrotic lesions. We diagnosed the patient
      as having neuromyelitis optica (NMO) because of the seropositivity for anti-AQP4
      antibodies and on the basis of above-mentioned other immunohistochemical
      findings. It is difficult to distinguish NMO from ADEM clinically, when the
      patient has a preceding infection. NMO should be considered in patients with
      multifocal lesions in the central nervous system who have prominent myelitis and
      optic neuritis, irrespective of the postinfectious onset of the lesions and the
      sex and age of the patient.

PMID- 21878725
TI  - [A case of late-onset aqueductal membranous occlusion and a successful treatment
      with neuro-endoscopic surgery].
AB  - A 57 year-old man developed broad-based unsteady gait and memory loss over a
      period of one year. On admission, bradykinesia and impairment of postural reflex
      were evident. Mini-mental state examination scored 27/ 30. Urinary control was
      normal. MRI revealed symmetric dilatation of lateral and 3rd ventricles, but the
      4th ventricle appeared normal. Partial obstruction of the aqueduct with a
      membranous structure was disclosed by fast imaging employing steady state
      acquisition (FIESTA), and the diagnosis of late-onset aqueductal membranous
      occlusion (LAMO) was made. The symptoms were ameliorated shortly after endoscopic
      aqueductoplasty (EAP) and endoscopic third ventriculostomy (ETV). Membranous
      occlusion of the aqueduct can be detected by FIESTA and it can be cured by neuro
      endoscopic measures.

PMID- 21878726
TI  - [A case of Charles Bonnet syndrome following syphilitic optic neuritis].
AB  - Charles Bonnet syndrome refers to visual hallucinations in patients with visual
      acuity loss or visual field loss without dementia. We report a case of Charles
      Bonnet syndrome following syphilitic optic neuritis. A 62-year-old man was
      admitted to our hospital suffering acute bilateral visual loss in a few months.
      On admission, he was almost blind and his optic discs were found to be atrophic
      on fundoscopy. In addition to increased cell counts and protein concentration in
      cerebrospinal fluid (CSF), serum and CSF rapid plasma reagin tests were positive.
      A diagnosis of syphilitic optic neuritis was made and he was treated with
      intravenous penicillin G (24 million units per day for 14 days) without any
      recovery. After treatment finished, he began to experience complex, vivid,
      elaborate and colored visual hallucinations. He recognized these visions as
      unreal and felt distressed by them. No cognitive impairment was observed on
      several neuropsychological tests. We diagnosed the patient as suffering from
      Charles Bonnet syndrome. Brain MRI revealed diffuse mild atrophy of the cerebral
      cortex and multiple T2 high signal intensity lesions in the deep cerebral white
      matter. Single photon emission computed tomography revealed decreased regional
      cerebral blood flow in bilateral medial occipital lobes. Administration of
      olanzapine resulted in a partial remission of visual hallucinations. Charles
      Bonnet syndrome following syphilitic optic neuritis is rare. In the present case,
      visual loss and dysfunction of bilateral medial occipital lobes may have
      triggered the visual hallucinations, which were alleviated by olanzapine.

PMID- 21878727
TI  - [Neuromyelitis optica with syndrome of inappropriate secretion of antidiuretic
      hormone and hypersomnia associated with bilateral hypothalamic lesions: a case
      report].
AB  - A 31-year-old woman with a 5-year history of recurrent optic neuritis and
      encephalomyelitis underwent repeated steroid therapy. She developed general
      malaise and fever in October 2009. Laboratory tests revealed marked reduction in
      serum Na (106 mEq/L). Because the plasma osmotic pressure was lower than the
      urinary osmotic pressure and the serum antidiuretic hormone (ADH) level was
      elevated, she was diagnosed with the syndrome of inappropriate secretion of
      antidiuretic hormone (SIADH). Magnetic resonance imaging (MRI) revealed high
      signal intensities on symmetrical T2 weighted and fluid attenuated inversion
      recovery (FLAIR) images of both sides of the hypothalamus. The serum samples
      tested positive for the antibody to aquaporin-4 (AQP4). Previously conducted
      cervical MRI had revealed a longitudinally extending lesion in the cervical cord,
      and brain MRI had revealed brainstem lesions. We diagnosed the patient with
      neuromyelitis optica (NMO) according to the revised diagnostic criteria for NMO
      proposed by Wingerchuk in 2006. Furthermore, she complained of excessive daytime
      sleepiness. The concentration of orexin in the cerebrospinal fluid was mildly
      reduced and the orexin levels returned to normal when her sleepiness decreased.
      ADH and orexin neurons localized in the hypothalamus; hence, we considered the
      above-mentioned symptoms to be caused by bilateral hypothalamic lesions.

PMID- 21878728
TI  - [Magnetic resonance imaging with 21.1 T and pathological correlations--diffuse
      Lewy body disease].
AB  - We investigated fixed basal ganglia specimens, including globus pallidus and
      putamen, with 21.1-Tesla MRI allowing us to achieve a microscopic level
      resolution from a patient with pathologically confirmed dementia with Lewy bodies
      (DLB) and a neurologically normal control case. We acquired T2 and T2 * weighted
      images that demonstrated diffuse and patchy lower intensities in the basal
      ganglia compared to control. There are several paramagnetic substances in brain
      tissue that could potentially reduce both T2 and T2 * relaxation times, including
      ferritin, iron (Fe3+), manganese, copper and others. Because iron is most
      abundant, low intensities on T2 and T2 * weighted images most likely reflect iron
      deposition. Iron, especially Fe3+, deposition was visible in the pathological
      specimens stained with Prussian blue after images were obtained. Although
      radiological-pathological comparisons are not straightforward with respect to
      either the MRI signal or relaxation quantification, there appears to be a
      correlation between the relative increase in iron as assessed by Prussian blue
      staining and the decrease in T2 * value between the DLB and control specimens. As
      such, this exceptionally high field MRI technique may provide details about the
      role that iron deposition plays either directly or indirectly as a biomarker in
      neurodegenerative processes.

PMID- 21878729
TI  - [Villaret's syndrome caused by internal carotid artery dissection].
AB  - We report a patient with Villaret's syndrome (left hypoglossopharyngeal nerve,
      vagus nerve, accessory nerve, and hypoglossal nerve palsies and left Horner's
      sign) caused by internal carotid artery dissection. He had neck pain on the left
      side, Horner's sign on the left side and paralysis of the left
      hypoglossopharyngeal nerve, vagus nerve, accessory nerve, and hypoglossal nerve.
      Brain MRI revealed no signal from the left internal carotid artery and no brain
      infarction, although a tumor-like lesion was observed in the left internal
      carotid artery. Subsequent MRI studies revealed intramural hematoma in the left
      internal carotid artery, and on the basis of this finding, he was diagnosed with
      internal carotid artery dissection. He received anticoagulant and antiplatelet
      therapy. His symptoms improved gradually. The symptoms of internal carotid artery
      dissection are neck pain, Horner's sign, brain infarction, and lower cranial
      nerve palsy. A characteristic feature in this case was that brain infarction was
      not observed. Only 3 similar cases have been reported in the past In all these
      cases, the patients had a good clinical course and showed complete recovery from
      the symptoms. Compared with western countries, in Japan, carotid artery
      dissection is rare. Carotid artery dissection should be considered as a
      differential diagnosis of lower cranial nerve palsy.

PMID- 21878730
TI  - [A system to enforce multicenter clinical trials with public funds: introduction
      of a neurological cooperative group in the United States].
AB  - Success of a multicenter clinical trial relies on the good and stable support
      system including a number of experienced people and sufficient funds. In Japan,
      lack of the experienced and well-funded support system makes conducting of the
      multicenter clinical trials very difficult. In the US, substantial amount of
      governmental funds have been injected to develop the clinical trial
      infrastructure. The cooperative group system is a model of the US governmental
      funded clinical trial support system, in which the researchers can plan and
      conduct the clinical trials effectively and reliably, cooperating with other
      clinical research professionals including biostatisticians. Although there are
      some active oncology cooperative groups in Japan, this system remains unfamiliar
      to the researchers in neurology. It should be more noticed and utilized widely.

PMID- 21878731
TI  - Biochemical responses to dietary alpha-linolenic acid restriction proceed
      differently among brain regions in mice.
AB  - Previously, we noted that the dietary restriction of alpha-linolenic acid (ALA, n
      3) for 4 weeks after weaning brought about significant decreases in the BDNF
      content and p38 MAPK activity in the striatum of mice, but not in the other
      regions of the brain, compared with an ALA- and linoleic acid (LNA, n-6)-adequate
      diet. In this study, we examined whether a prolonged dietary manipulation induces
      biochemical changes in other regions of the brain as well. Mice were fed a
      safflower oil (SAF) diet (ALA-restricted, LNA-adequate) or a perilla oil (PER)
      diet (containing adequate amounts of ALA and LNA) for 8 weeks from weaning. The
      docosahexaenoic acid (DHA, 22:6n-3) contents and p38 MAPK activities in the
      cerebral cortex, striatum and hippocampus were significantly lower in the SAF
      group. The BDNF contents and protein kinase C (PKC) activities in the cerebral
      cortex as well as in the striatum, but not in the hippocampus, were significantly
      lower in the SAF group. These data indicate that the biochemical changes induced
      by the dietary restriction of ALA have a time lag in the striatum and cortex,
      suggesting that the signal is transmitted through decreased p38 MAPK activity and
      BDNF content and ultimately decreased PKC activity.

PMID- 21878732
TI  - Differentiation capacity of BrdU label-retaining dental pulp cells during pulpal
      healing following allogenic transplantation in mice.
AB  - Our recent study has demonstrated the localization of putative dental pulp stem
      cells in the developing molar by chasing 5-bromo-2'-deoxyuridine (BrdU)-labeling.
      However, their differentiation capacity subsequent to the tooth transplantation
      remains to be elucidated. This study aims to clarify the differentiation capacity
      of BrdU label-retaining dental pulp cells and their relationship to cell
      proliferation and apoptosis during pulpal healing following allogenic
      transplantation in mice. Following extraction of the mouse molar in BrdU-labeled
      animals, the roots and pulp floor were resected and immediately allo-grafted into
      the sublingual region in non-labeled animals, and vice versa. In the labeled
      transplants, label-retaining cells (LRCs) were increased in number and committed
      in nestin-positive newly differentiated odontoblast-like cells, whereas they were
      not committed in osteoblast-like cells. In the labeled host, on the contrary,
      LRCs were committed in neither odontoblast- nor osteoblast-like cells, although
      they were transiently increased in number and finally disappeared in the pulp
      tissue of the transplants. Interestingly, numerous apoptotic cells appeared in
      the pulp tissue including LRCs during the experimental period. These results
      suggest that transplanted LRCs maintain their proliferative and differentiation
      capacity in spite of extensive apoptosis occurring in the transplant, whereas
      transiently increased host-derived LRCs finally disappear in the pulp chamber
      following apoptosis.

PMID- 21878733
TI  - Morphological assessment of bone mineralization in tibial metaphyses of ascorbic
      acid-deficient ODS rats.
AB  - Osteogenic disorder shionogi (ODS) rats carry a hereditary defect in ascorbic
      acid synthesis, mimicking human scurvy when fed with an ascorbic acid-deficient
      (aa-def) diet. As aa-def ODS rats were shown to feature disordered bone
      formation, we have examined the bone mineralization in this rat model. A fibrous
      tissue layer surrounding the trabeculae of tibial metaphyses was found in aa-def
      ODS rats, and this layer showed intense alkaline phosphatase activity and
      proliferating cell nuclear antigen-immunopositivity. Many osteoblasts detached
      from the bone surfaces and were characterized by round-shaped rough endoplasmic
      reticulum (rER), suggesting accumulation of malformed collagen inside the rER.
      Accordingly, fine, fragile fibrillar collagenous structures without evident
      striation were found in aa-def bones, which may result from misassembling of the
      triple helices of collagenous alpha-chains. Despite a marked reduction in bone
      formation, ascorbic acid deprivation seemed to have no effect on mineralization:
      while reduced in number, normal matrix vesicles and mineralized nodules could be
      seen in aa-def bones. Fine needle-like mineral crystals extended from these
      mineralized nodules, and were apparently bound to collagenous fibrillar
      structures. In summary, collagen mineralization seems unaffected by ascorbic acid
      deficiency in spite of the fine, fragile collagenous fibrils identified in the
      bones of our animal model.

PMID- 21878734
TI  - Impact of lumbar kyphosis on gastric myoelectrical activity and heart rate
      variability in a model using flexion posture in healthy young adults.
AB  - Relationship between lumbar kyphotic deformity and gastroesophageal reflux
      disease has been indicated in recent years. But it remains unclear whether
      kyphotic deformity of the lumbar vertebrae affects gastric motility. Healthy
      young adults (n = 20) were analyzed by recording the electrogastrography (EGG)
      and heart rate variability (HRV) before and after meal with flexion and neutral
      postures. Dominant power (DP) and dominant frequency (DF) of EGG and low
      frequency (LF) and high frequency (HF) of HRV were analyzed in blocks of 10
      minutes' duration. In neutral posture, DPs of all postprandial durations were
      significantly higher than those during fasting in two channels (P < 0.05, P <
      0.01). However, in flexion posture, only DP at postprandial 20 (10-20 minutes
      after eating) in a channel was significantly higher than that during fasting (P <
      0.05). DF in neutral posture was significantly higher than that in flexion
      posture at postprandial 20 in a channel (P < 0.05). The standard deviation of DF
      at postprandial 10 in flexion posture was significantly higher than that during
      fasting in a channel (P < 0.05). LF/HF in neural posture was significantly higher
      than that in flexion posture at postprandial 10 (P < 0.05). These findings
      suggest that inhibition of stomach myoelectrical activity was induced in the
      flexion posture in this lumbar kyphotic model, and autonomic activity as assessed
      by HRV did not accord with that expected from EGG.

PMID- 21878735
TI  - Capsiate, a non-pungent capsaicin analog, reduces body fat without weight rebound
      like swimming exercise in mice.
AB  - Enhancement of energy expenditure and reducing energy intake are crucial for
      weight control. Capsiate, a non-pungent capsaicin analog, is known to suppress
      body fat accumulation and reduce body weight by enhancing of energy expenditure
      in both mice and humans. However, it is poorly understood whether suppressing
      body fat accumulation by capsiate administration is equal to exercise or not. The
      aim of this study is to compare the effects of repeated administration of
      capsiate and exercise and to investigate the weight rebound after repeated
      capsiate administration and/or exercise. In the present study, we report that 2
      weeks treatment of capsiate and exercise increased energy metabolism and
      suppressed body fat accumulation during 4 more weeks of ad libitum feeding. The
      body weight in capsiate and exercise groups was significantly lower than that of
      control group. The oxygen consumption was significanlty increased in capsiate and
      exercise groups than in the vehicle administered mice. In addition, the abdominal
      adipose tissue weight in capsiate and exercise groups was significantly lower
      than that of control group. These results indicate that suppressing body fat
      accumulation by capsiate intake is beneficial for maintaining an ideal body
      weight as exercise.

PMID- 21878736
TI  - Osteoinductive and anti-inflammatory effect of royal jelly on periodontal
      ligament cells.
AB  - Royal jelly (RJ) has been reported to possess several physiological and
      pharmacological properties such as the ability to prevent osteoporosis in rats
      and anti-inflammatory effects. We hypothesized that RJ could have beneficial
      effects on the prevention or treatment of periodontal diseases, which are chronic
      inflammatory diseases caused by bacterial infection that result in resorption of
      the tooth-supporting bone. We assessed the effect of RJ on mineralization in
      mouse periodontal ligament cell clone 22 (MPDL22 cells), which are of an
      osteogenic and cementogenic lineage. The mRNA expression of osteopontin,
      osteocalcin and osterix, and mineralized nodule formation were significantly
      enhanced in RJ-treated MPDL22 cells. In addition, we investigated the effects of
      RJ on the production of inflammatory cytokines from MPDL22 cells stimulated with
      lipopolysaccharide (LPS) of Porphyromonas gingivalis, a periodontopathic
      bacterium. RJ suppressed LPS-induced interleukin-6 and CXC chemokine ligand 10
      production from MPDL22 cells. Furthermore, RJ suppressed the expression of CD54
      in MPDL22 cells: CD54 is the adhesion molecule involved in the accumulation of
      leukocytes in periodontal lesions. These findings suggest that the osteoinductive
      and anti-inflammatory effects of RJ can provide benefits for the treatment and
      prevention of periodontal diseases.

PMID- 21878737
TI  - Intensified expressions of a monocarboxylate transporter in consistently renewing
      tissues of the mouse.
AB  - Monocarboxylates-lactate and ketone bodies-can compensate for glucose as energy
      sources under certain physical conditions. To identify the main energy source
      used in self-renewing tissues, expression profiles of monocarboxylate
      transporters (MCTs) were mainly investigated immunohistochemically in the
      gastrointestinal tract, skin, and bone marrow of mice, with reference to glucose
      transporters. In the small intestine, MCT1-immunoreactive epithelial cells
      accumulated in crypts with a selective immunolabeling along the basolateral
      membrane of cells. BrdU-labeled dividing cells were included in the cryptal MCT1
      immunoreactive foci. The skin displayed an intense and extensive immunoreactivity
      for MCT1 in the hair bulge, which gives rise to the epidermis, hair, and
      sebaceous gland. The stratified squamous epithelium in the esophagus contained
      MCT1-immunoreactive cells in the basal layer but frequently lacked GLUT1
      immunoreactive cells. The bone marrow was largely immunoreactive for MCT1 but not
      for GLUT1, suggesting the active production and utilization of monocarboxylates
      for hematopoiesis under hypoxic conditions. These findings support the idea that
      monocarboxylates are favorite energy sources in self-renewing tissues.

PMID- 21878738
TI  - Paroxysmal atrial fibrillation and administration of antiplatelet therapy are
      still negative determinants of warfarin use in non-valvular atrial fibrillation
      patients treated by Japanese cardiologists.

PMID- 21878739
TI  - Induction of CYP1 family members under low-glucose conditions requires AhR
      expression and occurs through the nuclear translocation of AhR.
AB  - Cross-talk between the aryl hydrocarbon receptor (AhR) pathway and the typical
      stress response is thought to be an important signal transduction in response to
      nutrient-stress conditions, such as glucose deprivation in liver cells. In the
      present study, we demonstrate that reduction of glucose concentration in the
      medium of HepG2 cells, a human hepatocellular carcinoma cell line, induces the
      CYP1 family and Nrf2. RNAi for AhR abolishes the induction of expression of CYP1
      and Nrf2. These inductions are accompanied by the translocation of AhR into the
      nucleus in response to low-glucose conditions. Endogenous compounds are recruited
      as AhR ligands to induce various gene expressions, and our present results
      suggest that an endogenous AhR ligand is produced under low-glucose conditions
      and that the role of AhR as a transcription factor is related to the low-glucose
      response. The recommended glucose concentration (4.5 g/L) in the medium for
      culture of HepG2 was used as the high-glucose concentration in this study. We
      adopted 1.0 g/L as the low-glucose condition for elucidation of mechanisms of the
      stress response. These results will be useful to understand the relationship
      between drug-metabolizing enzymes and mechanisms of the anti-stress response of
      tumor cells, and will also be useful for investigating preventive remedies
      against tumor angiogenesis.

PMID- 21878740
TI  - Decreased expression of intestinal P-glycoprotein increases the analgesic effects
      of oral morphine in a streptozotocin-induced diabetic mouse model.
AB  - Morphine is one of the strongest analgesics and is commonly used for the
      treatment of chronic pain. The pharmacokinetic properties of morphine are, in
      part, modulated by P-glycoprotein (P-gp). We previously reported that intestinal
      P-gp expression levels are influenced via the activation of inducible nitric
      oxide synthase (iNOS) in streptozotocin (STZ)-induced diabetic mice. Herein, we
      examine the analgesic effects of orally administered morphine and its
      pharmacokinetic properties under diabetic conditions, specifically we focusing on
      the involvement of intestinal P-gp in a type 1 diabetic mouse model. We assessed
      the analgesic effect of morphine using the tail-flick test. Serum and brain
      morphine levels were determined using a HPLC-ECD system. Oral morphine analgesic
      effects and serum and brain morphine content were significantly increased 9 days
      after STZ administration. The increase in the analgesic effects of morphine, as
      well as serum and brain morphine content, was suppressed by aminoguanidine, a
      specific iNOS inhibitor. Conversely, there were no changes in the analgesic
      effects obtained with subcutaneous morphine in STZ-treated mice. Our findings
      suggest that the analgesic effects of oral morphine are dependent on intestinal P
      gp expression, and this may be one of the reasons that it is difficult to obtain
      stable pharmacological effects of morphine in diabetic patients.

PMID- 21878741
TI  - Prediction of the intestinal first-pass metabolism of CYP3A and UGT substrates in
      humans from in vitro data.
AB  - This study aimed to establish a practical and simplified method of predicting
      intestinal availability in humans (F(g,human)) at the drug discovery stage using
      in vitro metabolic clearance values and permeability clearance values. A
      prediction model for F(g,human) of 19 CYP3A substrates and 5 UGT substrates was
      constructed based on the concept that the permeability clearance values mean the
      permeability across the basal membrane with a pH of 7.4 on both sides.
      Permeability clearance values were obtained by parallel artificial membrane
      permeability assay (PAMPA) at pH 7.4. PAMPA is widely used in the pharmaceutical
      industry as the earliest primary screening stage and enables estimation of the
      kinetics of transport by passive diffusion. For CYP3A substrates, the metabolic
      clearance was obtained from in vitro intrinsic clearance values in human
      intestinal or hepatic microsomes (CL(int,HIM) or CL(int,HLM), respectively).
      Using metabolic clearances corrected by the ratio of CL(int,HIM) to CL(int,HLM),
      HLM showed equivalent predictability to that of HIM for CYP3A substrates. For UGT
      substrates, the clearance was obtained from alamethicin-activated HIM using one
      incubation with both NADPH and UDPGA cofactors. The method proposed in this study
      could predict F(g,human) for the compounds investigated and represents a
      simplified method based on a new concept applicable to lower permeability
      compounds.

PMID- 21878742
TI  - FAP associated cribriform morular variant of PTC: striking female prevalence and
      indolent course.

PMID- 21878743
TI  - Decreased active GLP-1 response following large test meal in patients with type 1
      diabetes using bolus insulin analogues.
AB  - Postprandial plasma immunoreactive active glucagon-like peptide-1 (p-active GLP
      1) levels in type 1 diabetic patients who did not use bolus insulin responded
      normally following ingestion of test meal, while a small response of p-active GLP
      1 levels was seen in type 2 diabetic patients. To determine whether p-active GLP
      1 levels are affected by ingestion of test meal in type 1 diabetic Japanese
      patients who used bolus rapid-acting insulin analogues, plasma glucose (PG),
      serum immunoreactive insulin (s-IRI), serum immunoreactive C-peptide (s-CPR), and
      p-active GLP-1 levels were measured 0, 30, and 60 min after ingestion of test
      meal in Japanese patients without diabetic complications (n=10, group 1) and
      control subjects with normal glucose tolerance (n=15, group 2). HbA1c levels were
      also measured in these groups. The patients in group 1 were treated with multiple
      daily injections or CSII using injections of bolus rapid-acting insulin analogues
      before ingestion of test meal.  There was no significant difference in mean of
      sex, age, or BMI between groups. Means of HbA1c, basal and postprandial PG, and
      postprandial s-IRI levels with integrated areas under curves (0-60 min) (AUC) in
      group 1 were significantly higher than those in group 2. Means of basal and
      postprandial s-CPR, and postprandial p-active GLP-1 levels with AUCs were
      significantly lower in group 1 than in group 2.  These results indicated that
      postprandial p-active GLP-1 levels following ingestion of test meal in type 1
      diabetic Japanese patients using bolus rapid-acting insulin analogues were
      decreased relative to those in controls.

PMID- 21878744
TI  - Resveratrol inhibits monocytic cell chemotaxis to MCP-1 and prevents spontaneous
      endothelial cell migration through Rho kinase-dependent mechanism.
AB  - AIM: Inflammatory cell recruitment and intimal neovascularization contribute to
      atherosclerotic plaque destabilization. The anti-inflammatory red wine
      polyphenol, resveratrol, has been implicated in cardiovascular protection. In
      this study, we investigated the effects of resveratrol on endothelial and
      monocytic cell migration. METHODS: Human umbilical vein endothelial cell (EC)
      migration was assessed in a modified barrier assay. Chemotaxis of THP-1 monocytic
      cells towards monocyte chemoattractant protein (MCP)-1 was determined using a
      Boyden chamber. Erk phosphorylation downstream of MCP-1 receptor and activation
      of myosin phosphatase targeting subunit 1 (pMYPT1) downstream of Rho kinase were
      determined by Western blotting. RESULTS: In resveratrol-treated cells,
      progressive shape elongation was observed, evident after 6h of treatment.
      Treatment with resveratrol (1-20 umol/L) dose-dependently inhibited EC migration.
      This effect of resveratrol was independent of nuclear factor (NF)-kappaB and
      sirtuin 1, but was abrogated in the presence of Rho kinase inhibitors. Moreover,
      resveratrol induced pMYPT1 activation, indicating a novel mechanism of
      resveratrol activity in EC. In monocytic cells, treatment with resveratrol
      significantly inhibited chemotaxis towards MCP-1 already at 1 umol/L. At a
      resveratrol concentration of 10 umol/L, chemotaxis was reduced nearly to the
      negative control (unstimulated with MCP-1) levels. This effect was independent of
      NF-kappaB and RhoA signaling. In resveratrol treated monocytic cells, MCP-1
      induced Erk phosphorylation downstream of CCR2 receptor was dose-dependently
      inhibited, as observed by Western blot analysis. CONCLUSIONS: Resveratrol dose
      dependently inhibited endothelial cell migration and MCP-1-induced monocytic cell
      chemotaxis. This activity may contribute to the cardioprotective effects of
      resveratrol by inhibition of intimal neovascularization and monocyte recruitment
      into the artery wall.

PMID- 21878745
TI  - Seasonal variation in Campylobacter-contaminated retail chicken products: a year
      round investigation in Japan.
AB  - Campylobacter was isolated from retail meat samples collected during the fiscal
      year 2009 in Japan. The higher percentages of contamination of chicken products
      were observed from June (39.3%) to November (83.3%). However, the highest number
      of human campylobacteriosis cases was reported in June in the Infectious Agents
      Surveillance Report. The chicken isolates with distinct clusters IVb and I, based
      on the restriction fragment length polymorphism of the flaA gene, were
      predominantly obtained during the periods between April and November 2009 and
      between February and March 2010, respectively. Extensive monitoring of
      Campylobacter contamination in chickens produced in various places is needed to
      analyse the seasonal variations between contamination of the meat products and
      the number of human cases with campylobacteriosis.

PMID- 21878746
TI  - Diagnosis of fulminant pneumonia caused by Legionella pneumophila serogroup 8
      with the sequence analysis of the 16S rRNA gene.
AB  - Pneumonia is the fourth leading cause of death in Japan. Accurate and rapid
      detection of the causative pathogen(s) is necessary and important for appropriate
      antimicrobial treatment, especially in patients with rapidly progressive
      pneumonia or immunocompromised patients. Conventional methods, such as
      cultivations, detection of urinary antigens or PCR amplification of specific
      genes, inevitably require the precise presumption of potential pathogens in each
      case, and pneumonia caused by unanticipated microorganisms might lead to
      inadequate antimicrobial treatments and unfortunate consequences. We herein
      report an immunocompromised female patient (69 years old) with fulminant
      pneumonia caused by Legionella (L.) pneumophila serogroup 8. Ordinary cultivation
      methods and urinary antigen detection failed to identify the causative organisms.
      Accordingly, DNA was extracted from the bronchoalveolar lavage fluid and used for
      the PCR-based cloning of the bacterial 16S rRNA gene. Sequencing analysis of the
      isolated clones revealed the predominance of L. pneumophila. Based on this
      information, the patient received an appropriate and successful antimicrobial
      treatment. In addition, L. pneumophila serogroup 8 was identified with culturing
      the bronchoalveolar lavage fluid and serotyping with L. pneumophila antisera. The
      16S rRNA gene sequencing analysis can reveal the potential pathogens without any
      presumption about the organism, and can evaluate the kinds and ratio of bacterial
      species in each specimen. In conclusion, this cultivation-independent method is a
      potential diagnostic modality for pneumonia, especially in patients with rapidly
      progressive pneumonia or those who are immunocompromised.

PMID- 21878747
TI  - Functional electrical therapy for hemiparesis alleviates disability and enhances
      neuroplasticity.
AB  - Impaired motor and sensory function is common in the upper limb in humans after
      cerebrovascular stroke and it often remains as a permanent disability. Functional
      electrical stimulation therapy is known to enhance the motor function of the
      paretic hand; however, the mechanism of this enhancement is not known. We studied
      whether neural plasticity has a role in this therapy-induced enhancement of the
      hand motor function in 20 hemiparetic subjects with chronic stroke (age 53 +/- 6
      years; 7 females and 13 males; 10 with cerebral infarction and 10 with cerebral
      haemorrhage; and time since incident 2.4 +/- 2.0 years). These subjects were
      randomized to functional electrical therapy or conventional physiotherapy group.
      Both groups received upper limb treatment (twice daily sessions) for two weeks.
      Behavioral hand motor function and neurophysiologic transcranial magnetic
      stimulation (TMS) tests were applied before and after the treatment and at 6
      months follow-up. TMS is useful in assessing excitability changes in the primary
      motor cortex. Faster corticospinal conduction and newly found muscular responses
      were observed in the paretic upper limb in the functional electrical therapy
      group but not in the conventional therapy group after the intervention.
      Behaviourally, faster movement times were observed in the functional electrical
      therapy group but not in the conventionally treated group. Despite the small
      number of heterogeneous subjects, functional exercise augmented with
      individualized electrical therapy of the paretic upper limb may enhance
      neuroplasticity, observed as corticospinal facilitation, in chronic stroke
      subjects, along with moderate improvements in the voluntary motor control of the
      affected limb.

PMID- 21878749
TI  - Synergistic efficacy of a novel combination therapy controls growth of Bcl-x(L)
      bountiful neuroblastoma cells by increasing differentiation and apoptosis.
AB  - Neuroblastoma is the most prevalent extracranial solid tumor mainly in pediatric
      patients. We explored the efficacy of the combination of 2[(3-[2,3
      dichlorophenoxy]propyl)amino]ethanol (2,3-DCPE, a small molecule inhibitor of the
      anti-apoptotic protein Bcl-x(L)) and N-(4-hydroxyphenyl) retinamide (4-HPR, a
      synthetic retinoid) in inducing differentiation and apoptosis in human malignant
      neuroblastoma cells. Immunofluorescence confocal microscopy and flow cytometry
      showed that the highest level of Bcl-x(L) expression occurred in SK-N-DZ cells
      followed by SH-SY5Y and IMR-32 cells. Combination of 20 MUM 2,3-DCPE and 1 MUM 4
      HPR acted synergistically in decreasing viability of SK-N-DZ and SH-SY5Y cells.
      In situ methylene blue staining and protein gel blotting showed the efficacy of
      this combination of drugs in inducing neuronal differentiation morphologically
      and also biochemically with upregulation of the neuronal markers such as
      neurofilament protein (NFP) and neuron specific enolase (NSE) and downregulation
      of the differentiation inhibiting molecules such as N-Myc and Notch-1 in SK-N-DZ
      and SH-SY5Y cells. Annexin V-FITC/PI staining showed the synergistic action of
      this combination therapy in increasing apoptosis in both cell lines. Protein gel
      blotting manifested that combination therapy increased apoptosis with
      downregulation of the anti-apoptotic proteins Bcl-x(L), Bcl-2 and Mcl-1 and
      upregulation of the pro-apoptotic proteins Bax, p53, Puma (p53 upregulated
      modulator of apoptosis), and Noxa, ultimately causing activation of caspase-3. In
      conclusion, our results appeared highly encouraging in advocating the use of 2,3
      DCPE and 4-HPR as a novel combination therapy for increasing both differentiation
      and apoptosis in human malignant neuroblastoma cells having Bcl-x(L)
      overexpression.

PMID- 21878748
TI  - Sorafenib attenuates p21 in kidney cancer cells and augments cell death in
      combination with DNA-damaging chemotherapy.
AB  - There are few effective therapeutic options for metastatic renal cell carcinoma
      (RCC). Conventional chemotherapeutic agents are ineffective since these tumors
      are unusually resistant to DNA damage, likely due to an exuberant DNA repair
      response. Sorafenib, as one of the few available effective therapeutic options
      for metastatic RCC, has been shown to inhibit cell proliferation by inhibition of
      tyrosine kinases. We have recently shown that sorafenib inhibits soluble epoxide
      hydrolase, which catalyzes metabolism of the anti-inflammatory
      epoxyeicosatrienoic acids. Given previous work demonstrating the anti-apoptotic
      role of p21 in RCC as a potential mechanism for its drug resistance, we asked
      whether sorafenib signals through this pathway. We now show that sorafenib
      markedly decreases p21 levels in several RCC and hepatocellular carcinoma cells.
      Neither the MEK inhibitor PD98059 nor the sEH inhibitor t-AUCB, which represent
      known sorafenib-targeted signaling pathways, alter p21 levels, demonstrating that
      the p21 inhibitory effect of sorafenib is independent of these signaling
      cascades. In cells treated with doxorubicin to augment p21, sorafenib markedly
      decreases this protein, and the combinations of paclitaxel or doxorubicin with
      sorafenib show additive cytotoxicity as a function of the VHL status of the
      cells, suggesting that lower doses of each agent could be used in the clinical
      setting. In summary, we show a novel signaling pathway by which sorafenib exerts
      its salutary effects in RCC; future work will focus on the use of these drug
      combinations in the context of conventional therapeutics, and novel compounds and
      protocols targeting p21 in conjunction with sorafenib should be pursued.

PMID- 21878750
TI  - Development of a biomimetic peptide derived from collagen IV with anti-angiogenic
      activity in breast cancer.
AB  - Breast cancer is one of the most commonly diagnosed malignancies in women.
      Despite the remarkable success of mammography screening and use of adjuvant
      systemic therapy, it is estimated that approximately 200,000 new diagnoses will
      be made this year and 40,000 deaths will occur due to this disease (American
      Cancer Society). Angiogenesis, the growth of vessels from pre-existing
      microvasculature, is an essential component of tumor progression and has emerged
      as a therapeutic modality for anti-angiogenic therapies in cancer. Here we report
      in vitro and in vivo findings with a 20 amino acid peptide belonging to the
      collagen IV family, modified to facilitate possible translation to clinical
      applications. The two cysteines in its natural peptide progenitor were replaced
      by L-alpha-amino-n-butyric acid, a non-natural amino acid. The modified peptide
      was tested in vitro using endothelial cells and in vivo using mouse orthotopic
      breast cancer xenograft model with MDA-MB-231 human breast cancer cells. This
      modified peptide demonstrated no significant changes in activity from the parent
      peptide; however, because it lacks cysteines, it is more suitable for clinical
      translation. We also investigated its efficacy in combination with a commonly
      used chemotherapeutic agent paclitaxel; the inhibition of tumor growth by the
      peptide was similar to that of paclitaxel alone, but the combination did not
      exhibit any additional inhibition. We have performed further characterization of
      the mechanism of action (MOA) for this peptide to identify its target receptors,
      enhancing its translation potential as an anti-angiogenic, non-vascular
      endothelial growth factor (VEGF) targeting agent for therapy in breast cancer.

PMID- 21878751
TI  - MicroRNA-30c promotes human adipocyte differentiation and co-represses PAI-1 and
      ALK2.
AB  - Obesity is characterized by excessive adipose tissue mass and associated with
      type 2 diabetes and cardiovascular diseases. To fight obesity and its sequels,
      elucidating molecular events that govern adipocyte differentiation and function
      is of key importance. MicroRNAs (miRNAs) are a novel class of non-coding,
      regulatory RNAs that have been shown to regulate crucial cellular processes,
      including differentiation. Several studies have already assigned miRNAs to
      distinct functions in murine adipocyte differentiation but only a few studies did
      so for humans.  Here, we investigated the function of miR-30c in human
      adipogenesis. miR-30c expression was increased during adipogenesis of human
      multipotent adipose-derived stem (hMADS) cells, and miR-30c overexpression
      enforced adipocyte marker gene induction and triglyceride accumulation. miRNA
      target prediction revealed two putative direct targets of miR-30c, PAI-1
      (SERPINE1) and ALK2 (ACVR1, ACTRI), both inversely regulated to miR-30c during
      adipogenesis and responsive to miR-30c overexpression. Luciferase reporter assays
      confirmed PAI-1 and ALK2 as direct miR-30c targets. Moreover, reciprocal
      expression between miR-30c and PAI-1 could also be demonstrated in white adipose
      tissue of obesity mouse models, suggesting a potential physiological role of miR
      30c for PAI-1 regulation in the obese state. Validating PAI-1 and ALK-2 as miR
      30c mediators in adipogenesis revealed that not single silencing of PAI-1 or
      ALK2, but only co-silencing of both phenocopied the pro-adipogenic miR-30c
      effect. Thus, miR-30c can target two, so far not interconnected genes in distinct
      pathways, supporting the idea that miRNAs might coordinate larger regulatory
      networks than previously anticipated.

PMID- 21878753
TI  - Current world literature.

PMID- 21878755
TI  - Is there a path for approval of an antiobesity drug: what did the Sibutramine
      Cardiovascular Outcomes Trial find?
AB  - PURPOSE OF REVIEW: Obesity continues to increase in prevalence in the USA and
      throughout the world. It is clearly a major contributor to morbidity and
      mortality. Unfortunately, effective prevention strategies are few. As a
      contributor to cardiovascular disease, obesity is an important treatment
      objective. However, before approval, all drugs must meet safety and efficacy
      concerns of the US Food and Drug Administration. RECENT FINDINGS: Since July
      2010, the Food and Drug Administration's Endocrine and Metabolic Advisory
      Committee has reviewed three new drug applications and one previously approved
      drug for the treatment of obesity. This review examines in detail the Advisory
      Committee's consideration of the risk-benefit equation of the four drugs with a
      concentration on sibutramine and its key study, Sibutramine Cardiovascular
      Outcomes Trial. SUMMARY: Future development of drugs for the treatment of obesity
      will be dependent on whether they can survive review for safety and
      effectiveness. The Food and Drug Administration continues to be highly concerned
      with proposed obesity drugs increasing cardiovascular or any risks and may
      require changes to clinical research protocols.

PMID- 21878756
TI  - Current world literature.

PMID- 21878757
TI  - To the heroes and professionals who helped protect the world from nuclear
      disasters and to those who were displaced by these catastrophes.

PMID- 21878758
TI  - Special issue introduction. The Chernobyl Center for Nuclear Safety, Radioactive
      Waste and Radioecology.

PMID- 21878759
TI  - Overview of the cooperation between the Chernobyl Center's International
      Radioecology Laboratory in Slavutych, Ukraine, and U.S. research centers between
      2000 and 2010.
AB  - The International Radioecology Laboratory (IRL) located in Slavutych, Ukraine,
      was created in 1999 under the initiative of the United States Government and the
      Government of Ukraine in the framework of international cooperation on evaluation
      and minimization of consequences of the Chernobyl nuclear power plant (ChNPP)
      accident. Since the time the IRL was founded, it has participated in a large
      number of projects, including the following: 1) study of radionuclide
      accumulation, distribution, and migration in components of various ecological
      systems of the Chernobyl Exclusion Zone (ChEZ); 2) radiation dose assessments; 3)
      study of the effects of radiation influence on biological systems; 4) expert
      analysis of isotopic and quantitative composition of radioactive contaminants; 5)
      development of new methods and technologies intended for radioecological
      research; 6) evaluation of future developments and pathways for potential
      remediation of the ChEZ areas; 7) assistance in provision of physical protection
      systems for ionizing irradiation sources at Ukrainian enterprises; 8) reviews of
      open Russian language publications on issues associated with consequences of the
      ChNPP accident, radioactive waste management, radioecological monitoring, and
      ChNPP decommissioning; 9) conduct of training courses on problems of
      radioecology, radiation safety, radioecological characterization of test sites
      and environmental media, and research methods; 10) conduct of on-site scientific
      conferences and workshops on the ChEZ and radioecology problems; participation in
      off-site scientific conferences and meetings; and 11) preparation of scientific
      and popular science publications and interactions with mass media
      representatives. This article provides a brief overview of the major achievements
      resulting from this cooperation between the IRL and U.S. research centers.

PMID- 21878760
TI  - Radiation dose assessment for the biota of terrestrial ecosystems in the
      shoreline zone of the Chernobyl nuclear power plant cooling pond.
AB  - Radiation exposure of the biota in the shoreline area of the Chernobyl Nuclear
      Power Plant Cooling Pond was assessed to evaluate radiological consequences from
      the decommissioning of the Cooling Pond. This paper addresses studies of
      radioactive contamination of the terrestrial faunal complex and radionuclide
      concentration ratios in bodies of small birds, small mammals, amphibians, and
      reptiles living in the area. The data were used to calculate doses to biota using
      the ERICA Tool software. Doses from 90Sr and 137Cs were calculated using the
      default parameters of the ERICA Tool and were shown to be consistent with biota
      doses calculated from the field data. However, the ERICA dose calculations for
      plutonium isotopes were much higher (2-5 times for small mammals and 10-14 times
      for birds) than the doses calculated using the experimental data. Currently, the
      total doses for the terrestrial biota do not exceed maximum recommended levels.
      However, if the Cooling Pond is allowed to draw down naturally and the
      contaminants of the bottom sediments are exposed and enter the biological cycle,
      the calculated doses to biota may exceed the maximum recommended values. The
      study is important in establishing the current exposure conditions such that a
      baseline exists from which changes can be documented following the lowering of
      the reservoir water. Additionally, the study provided useful radioecological data
      on biota concentration ratios for some species that are poorly represented in the
      literature.

PMID- 21878761
TI  - Vertical migration of radionuclides in the vicinity of the chernobyl confinement
      shelter.
AB  - Studies of vertical migration of Chernobyl-origin radionuclides in the 5-km zone
      of the Chernobyl Nuclear Power Plant (ChNPP) in the area of the Red Forest
      experimental site were completed. Measurements were made by gamma spectrometric
      methods using high purity germanium (HPGe) detectors with beryllium windows.
      Alpha-emitting isotopes of plutonium were determined by the measurement of the x
      rays from their uranium progeny. The presence of 60Co, 134,137Cs, 154,155Eu, and
      241Am in all soil layers down to a depth of 30 cm was observed. The presence of
      137Cs and 241Am was noted in the area containing automorphous soils to a depth of
      60 cm. In addition, the upper soil layers at the test site were found to contain
      243Am and 243Nm. Over the past 10 years, the 241Am/137Cs ratio in soil at the
      experimental site has increased by a factor of 3.4, nearly twice as much as would
      be predicted based solely on radioactive decay. This may be due to "fresh"
      fallout emanating from the ChNPP Confinement Shelter.

PMID- 21878762
TI  - Assessment of the radionuclide composition of "hot particles" sampled in the
      Chernobyl nuclear power plant fourth reactor unit.
AB  - Fuel-containing materials sampled from within the Chernobyl Nuclear Power Plant
      (ChNPP) Unit 4 Confinement Shelter were spectroscopically studied for gamma and
      alpha content. Isotopic ratios for cesium, europium, plutonium, americium, and
      curium were identified, and the fuel burn-up in these samples was determined. A
      systematic deviation in the burn-up values based on the cesium isotopes in
      comparison with other radionuclides was observed. The studies conducted were the
      first ever performed to demonstrate the presence of significant quantities of
      242Cm and 243Cm. It was determined that there was a systematic underestimation of
      activities of transuranic radionuclides in fuel samples from inside of the ChNPP
      Confinement Shelter, starting from 241Am (and going higher) in comparison with
      the theoretical calculations.

PMID- 21878763
TI  - Effects of ionizing radiation on the antioxidant system of microscopic fungi with
      radioadaptive properties found in the Chernobyl exclusion zone.
AB  - Some microscopic fungi found in the area of the Chernobyl Exclusion Zone appear
      to have unique radioadaptive properties associated with their capability to
      respond positively to the effects of ionizing irradiation. On the one hand, this
      capability can be used potentially in bio-remediation technologies, and on the
      other hand, it requires additional, more thorough studies to identify its
      underlying mechanisms. Practically, no data are currently available on mechanisms
      for implementation of these radioadaptive properties by microscopic fungi. The
      objective of the completed study was to evaluate the functioning of the
      antioxidant system of a microscopic fungus as one of potential mechanisms for
      implementation of its radioadaptive properties. The study was performed using a
      model system simulating the soil radioactivity in the 5-km zone around the
      Chernobyl Nuclear Power Plant, with the ratio of the radioactive isotopes
      matching the radionuclide content in the fuel component of the Chernobyl fallout.
      The completed study was the first ever performed to identify a comprehensive
      response of the major components of the antioxidant system of the microscopic
      fungi to ionizing radiation, resulting in an induced melanin synthesis and
      increased activity of the known enzymes of antioxidant protection. Their response
      to ionizing radiation depended on the presence or absence of radioadaptive
      properties and phase of the fungal growth. Fungi with radioadaptive properties
      have a much higher susceptibility for inducing synthesis of melanin and
      antioxidant enzymes than fungi without radioadaptive properties (hereinafter
      referred to as the reference species or strains), which illustrates the
      contribution of these processes to "radiophilia" of the fungi.

PMID- 21878764
TI  - Method for simultaneous 90Sr and 137Cs in-vivo measurements of small animals and
      other environmental media developed for the conditions of the Chernobyl exclusion
      zone.
AB  - To perform in vivo simultaneous measurements of the 90Sr and 137Cs content in the
      bodies of animals living in the Chernobyl Exclusion Zone (ChEZ), an appropriate
      method and equipment were developed and installed in a mobile gamma beta
      spectrometry laboratory. This technique was designed for animals of relatively
      small sizes (up to 50 g). The 90Sr content is measured by a beta spectrometer
      with a 0.1-mm-thick scintillation plastic detector. The spectrum processing takes
      into account the fact that the measured object is "thick-layered" and contains a
      comparable quantity of 137Cs, which is a characteristic condition of the ChEZ.
      The 137Cs content is measured by a NaI scintillation detector that is part of the
      combined gamma beta spectrometry system. For environmental research performed in
      the ChEZ, the advantages of this method and equipment (rapid measurements,
      capability to measure live animals directly in their habitat, and the capability
      of simultaneous 90Sr and 137Cs measurements) far outweigh the existing
      limitations (considerations must be made for background radiation and the animal
      size, skeletal shape, and body mass). The accuracy of these in vivo measurements
      is shown to be consistent with standard spectrometric and radiochemical methods.
      Apart from the in vivo measurements, the proposed methodology, after a very
      simple upgrade that is also described in this paper, works even more accurately
      with samples of other media, such as soil and plants.

PMID- 21878765
TI  - Chronic irradiation of Scots pine trees (Pinus sylvestris) in the Chernobyl
      exclusion zone: dosimetry and radiobiological effects.
AB  - To identify effects of chronic internal and external radiation exposure for
      components of terrestrial ecosystems, a comprehensive study of Scots pine trees
      in the Chernobyl Exclusion Zone was performed. The experimental plan included
      over 1,100 young trees (up to 20 y old) selected from areas with varying levels
      of radioactive contamination. These pine trees were planted after the 1986
      Chernobyl Nuclear Power Plant accident mainly to prevent radionuclide
      resuspension and soil erosion. For each tree, the major morphological parameters
      and radioactive contamination values were identified. Cytological analyses were
      performed for selected trees representing all dose rate ranges. A specially
      developed dosimetric model capable of taking into account radiation from the
      incorporated radionuclides in the trees was developed for the apical meristem.
      The calculated dose rates for the trees in the study varied within three orders
      of magnitude, from close to background values in the control area (about 5 mGy y(
      1)) to approximately 7 Gy y(-1) in the Red Forest area located in the immediate
      vicinity of the Chernobyl Nuclear Power Plant site. Dose rate/effect
      relationships for morphological changes and cytogenetic defects were identified,
      and correlations for radiation effects occurring on the morphological and
      cellular level were established.

PMID- 21878766
TI  - Frequency distributions of 90Sr and 137Cs concentrations in an ecosystem of the
      "Red Forest" area in the Chernobyl exclusion zone.
AB  - In the most highly contaminated region of the Chernobyl Exclusion Zone, the "Red
      Forest" site, the accumulation of the major dose-affecting radionuclides (90Sr
      and 137Cs) within the components of an ecological system encompassing 3,000 m(2)
      was characterized. The sampled components included soils (top 0-10 cm depth),
      Molina caerulea (blue moor grass), Camponotus vagus (carpenter ants), and
      Pelobates fuscus (spade-footed toad). In a comparison among the components of
      this ecosystem, the 90Sr and 137Cs concentrations measured in 40 separate grids
      exhibited significant differences, while the frequency distribution of the values
      was close to a logarithmically-normal leptokurtic distribution with a significant
      right-side skew. While it is important to identify localized areas of high
      contamination or "hot spots," including these values in the arithmetic mean may
      overestimate the exposure risk. In component sample sets that exhibited
      logarithmically normal distribution, the geometric mean more accurately
      characterizes a site. Ideally, risk assessment is most confidently achieved when
      the arithmetic and geometric means are most similar, meaning the distribution
      approaches normal. Through bioaccumulation, the highest concentrations of 90Sr
      and 137Cs were measured in the blue moor grass and spade-footed toad. These
      components also possessed distribution parameters that shifted toward a normal
      distribution.

PMID- 21878767
TI  - Radiation ecology issues associated with murine rodents and shrews in the
      Chernobyl exclusion zone.
AB  - This article describes major studies performed by the Chernobyl Center's
      International Radioecology Laboratory (Slavutich, Ukraine) on radioecology of
      murine rodents and shrews inhabiting the Chernobyl Exclusion Zone. The article
      addresses the long-term (1986-2005) and seasonal dynamics of radioactive
      contamination of animals and reviews interspecies differences in radionuclide
      accumulations and factors affecting the radionuclide accumulations. It is shown
      that bioavailability of radionuclides in the "soil-to-plant" chain and a trophic
      specialization of animals play key roles in determining their actual
      contamination levels. The total absorbed dose rates in small mammals
      significantly reduced during the years following the Chernobyl Nuclear Power
      Plant accident. In 1986, the absorbed dose rate reached 1.3-6.0 Gy h(-1) in the
      central areas of the Chernobyl Exclusion Zone (the "Red Forest"). In 1988 and
      1990, the total absorbed dose rates were 1.3 and 0.42 Gy h(-1), respectively. In
      1995, 2000, and 2005, according to the present study, the total absorbed dose
      rates rarely exceeded 0.00023, 0.00018, and 0.00015 Gy h(-1), respectively.
      Contributions of individual radiation sources into the total absorbed dose are
      described.

PMID- 21878768
TI  - Radioactive waste management in the Chernobyl exclusion zone: 25 years since the
      Chernobyl nuclear power plant accident.
AB  - Radioactive waste management is an important component of the Chernobyl Nuclear
      Power Plant accident mitigation and remediation activities in the so-called
      Chernobyl Exclusion Zone. This article describes the localization and
      characteristics of the radioactive waste present in the Chernobyl Exclusion Zone
      and summarizes the pathways and strategy for handling the radioactive waste
      related problems in Ukraine and the Chernobyl Exclusion Zone and, in particular,
      the pathways and strategies stipulated by the National Radioactive Waste
      Management Program.

PMID- 21878772
TI  - 200th volume of the Journal of Nervous and Mental Disease.

PMID- 21878769
TI  - Environmental radiation monitoring in the Chernobyl exclusion zone--history and
      results 25 years after.
AB  - This paper describes results of the radiation environmental monitoring performed
      in the Chernobyl Exclusion Zone (ChEZ) during the period following the 1986
      Chernobyl Nuclear Power Plant accident. This article presents a brief overview of
      five comprehensive reports generated under Contract No. DE-AC09-96SR18500
      (Washington Savannah River Company LLC, Subcontract No. AC55559N, SOW No. ON8778)
      and summarizes characteristics of the ChEZ and its post-accident status. The
      history of development of the radiation monitoring research in the ChEZ is
      described also. This paper addresses the characteristics of radiation monitoring
      in the ChEZ, its major goals and objectives, and changes in these goals and
      objectives in the course of time, depending on the tasks associated with the
      phase of mitigation of the ChNPP accident consequences. The results of the
      radiation monitoring in the ChEZ during the last 25 years are also provided.

PMID- 21878773
TI  - Merits and motives of the movement for asylum reform. 1878. J Nerv Ment Dis.
      5(4):694-714.

PMID- 21878774
TI  - A premature obituary: Edward C. Spitzka and the American psychiatry of 1878.
AB  - On March 4, 1878, at a meeting of the New York Neurological Society, Edward C.
      Spitzka delivers a blistering attack on psychiatry, basically dismissing all
      alienists as incompetent and indicating that "the study of insanity should be
      considered a subdivision of neurology." This address was published in the Journal
      of Nervous and Mental Disease in 1878 and reproduced in the current issue of the
      journal.Spitzka asserts that "nothing worthy of notice has proceeded from our
      insane asylums" and that asylum superintendents may be experts in many things,
      but they are not experts in the "diagnosis, pathology, and treatment of
      insanity." To ascertain whether or not Spitzka's characterizations were correct,
      I examined the medical and psychiatric literature published in English only in
      1878.This review indicates that Spitzka was largely wrong. Research was not what
      it should have been, and the alienists (psychiatrists of that era) knew it.
      American alienists, however, were otherwise engaged in all manner of
      deliberations about important issues of the day relevant to the practice of
      psychiatry. In fact, to an absolutely remarkable degree, the issues of 1878 are
      the same as those of American psychiatry in the 21st century. That might say much
      more about psychiatry than Spitzka could ever have known 133 years ago.

PMID- 21878775
TI  - Asylum reform and the great comeuppance of 1894--or was it?
AB  - The July 1894 issue of Journal of Nervous and Mental Disease published S. Weir
      Mitchell's address to the 50th meeting of asylum superintendents, the American
      Medico-Psychological Association, which had convened in Philadelphia in May. A
      reluctant but unapologetic Mitchell criticized the asylum doctors for their
      isolationism and backward ways. This article reviews Mitchell's critique of
      psychiatry and the responses to it during the next 50 years. Analyses of the
      critique by Adolf Meyer and others show that reform was already underway in 1894.
      Although Mitchell is often credited with delivering psychiatry a wake-up call, it
      is equally feasible that he was merely channeling the organic reforms from within
      the profession.

PMID- 21878776
TI  - Predictors of treatment response in Canadian combat and peacekeeping veterans
      with military-related posttraumatic stress disorder.
AB  - Military-related posttraumatic stress disorder (PTSD) is a significant
      psychiatric condition associated with severe psychosocial dysfunction. This study
      examined the predictors of treatment outcome in a group of veterans with military
      related PTSD. Participants were 102 Canadian combat and peacekeeping veterans who
      received treatment at a specialized outpatient clinic for veterans with
      psychiatric disorders resulting from military operation. Analysis demonstrated a
      significant decrease in PTSD severity during the 1-year period (Yuan-Bentler chi
      [86, N = 99] = 282.45, p < 0.001). We did not find chronicity, alcohol use, and
      anxiety or depression severity as significant predictors for PTSD symptom
      decline. However, initial depression significantly predicted anxiety symptom
      decline, and initial anxiety predicted depression symptom decline. This study
      demonstrated that, despite considerable comorbidity, significant treatment gains,
      including remission of PTSD, can be achieved in an outpatient setting in veterans
      with chronic military-related PTSD.

PMID- 21878777
TI  - Effects of chronic posttraumatic stress disorder on metabolic risk, quality of
      life, and stress hormones in aging former refugee children.
AB  - It is still unclear whether the association between traumatic stress and physical
      disease is mediated by posttraumatic stress disorder (PTSD). Therefore, we
      examined the long-term consequences of PTSD on cardiovascular risk, stress
      hormones, and quality of life in a sample of former refugee children who were
      severely traumatized more than six decades ago. In 25 subjects with chronic PTSD
      and 25 trauma-controlled subjects, we measured the variables of metabolic
      syndrome supplemented by the ankle-brachial index and highly sensitive C-reactive
      protein. Quality of life was assessed using the 36-item Short-Form Health Survey.
      Cortisol, adrenocorticotropin-releasing hormone (ACTH), and
      dehydroepiandrosterone (DHEA) were measured using the low-dose-dexamethasone
      suppression test. In addition, salivary cortisol was assessed at 8:00 a.m., 12:00
      p.m., 4:00 p.m., and 8:00 p.m. We found a significant group effect between
      participants with and without PTSD regarding quality of life but not in any
      metabolic parameter including the ankle-brachial index or cortisol, ACTH, and
      DHEA in plasma before and after dexamethasone or salivary cortisol. The
      postulated association between traumatic stress and physical illness does not
      appear to be mediated by PTSD in this population. Nevertheless, the search for
      subgroups of PTSD patients with childhood traumatization leading to different
      metabolic and endocrine long-term consequences in aging PTSD patients is needed.

PMID- 21878778
TI  - Developing treatments of persistent persecutory delusions: the impact of an
      emotional processing and metacognitive awareness intervention.
AB  - Worry has been implicated in increasing the levels of distress associated with
      persecutory delusions. It may partly cause this distress via the impediment of
      emotional processing of upsetting experiences. The clinical implication is that
      enhancing emotional processing of paranoid experiences will reduce distress. We
      therefore piloted a new brief intervention-the Emotional Processing and
      Metacognitive Awareness (EPMA)-on 12 patients with persistent persecutory
      delusions. The intervention was predominately influenced by written emotional
      disclosure and lasted for three sessions. The delusions were assessed at
      baseline, preintervention and postintervention and during a one-month follow-up.
      It was found that EPMA particularly reduced levels of delusion distress, and this
      was maintained at follow-up. The effect sizes were large but were likely
      overestimated given the absence of a control group and assessments that were not
      blind. These preliminary findings suggest that simply encouraging patients to
      talk, in the right way, about their delusions can be beneficial.

PMID- 21878779
TI  - A two-year cross-sectional study on the information about schizophrenia divulged
      by a prestigious daily newspaper.
AB  - Media is an important source of information about mental health for the public.
      The current study analyzed the information about schizophrenia divulged by the
      largest Brazilian newspaper. A content analysis examined articles on health and
      news involving affected individuals or suspected cases. The articles were rated
      against indicators of poor quality reporting and of effective health
      communication. The presence of myths was examined. The search identified 687
      articles, 75 of which fulfilled the inclusion/exclusion criteria and were
      selected. The themes with the highest number of articles were mental disorders
      and violence, treatment, and etiology. Three articles described the social
      inclusion stories of affected individuals. The coverage addressed genetic
      factors, drug-induced psychosis risk, and antipsychotic benefits, which may
      contribute to stigma reduction toward treatment. However, the articles divulged
      stigmatizing messages, and the entire complexity of the disorder was not
      discussed. Dangerousness was a common theme, which may invalidate positive
      messages about social inclusion.

PMID- 21878780
TI  - Self-perceived needs are related to violent behavior among schizophrenia
      outpatients.
AB  - This study assessed the relationship between self-perceived clinical and social
      needs and aggressive behavior in outpatients with schizophrenia. A total of 895
      outpatients with schizophrenia were enrolled. The presence of aggressive episodes
      was assessed using the Modified Overt Aggression Scale. Self-perceived needs were
      assessed using the Camberwell Assessment of Need in six areas of needs (food,
      household skills, self-care, daytime activities, psychotic symptoms, satisfaction
      with treatment, and company). The most common areas of needs were "psychotic
      symptoms" (81.6%), "daytime activities" (60.6%), and "household skills" (57.5%).
      More needs were expressed by patients who had more severe illnesses (p < 0.001)
      and more aggressive behavior (p < 0.001). Multivariate analysis showed that, in
      schizophrenia outpatients, self-perceived needs were associated with aggressive
      behavior (adjusted odds ratio, 11.43; 95% confidence interval, 5.11 to 25.56).
      Appropriate compliance with antipsychotic treatment was related with lower
      aggressive behavior (p < 0.001).

PMID- 21878781
TI  - Intrinsic motivation as a predictor of work outcome after vocational
      rehabilitation in schizophrenia.
AB  - Intrinsic motivation is a construct commonly used in explaining goal-directed
      behavior. In people with schizophrenia, intrinsic motivation is usually subsumed
      as a feature of negative symptoms or underlying neurocognitive dysfunction. A
      growing literature reflects an interest in defining and measuring motivational
      impairment in schizophrenia and in delineating the specific role of intrinsic
      motivation as both an independent predictor and a mediator of psychosocial
      functioning. This cross-sectional study examined intrinsic motivation as a
      predictor of vocational outcomes for 145 individuals with schizophrenia and
      schizoaffective disorder participating in a 6-month work rehabilitation trial.
      Correlation and mediation analyses examined baseline intrinsic motivation and
      negative symptoms in relation to work hours and work performance. Data support a
      significant relationship between intrinsic motivation and negative symptoms and
      significant correlations with outcome variables, such that lower negative
      symptoms and greater intrinsic motivation were associated with better work
      functioning. Moreover, in this sample, intrinsic motivation fully mediated the
      relationships between negative symptoms, work productivity, and work performance.
      These results have significant implications on the design of work rehabilitation
      interventions for people with schizophrenia and support a role for targeting
      intrinsic motivation directly to influence vocational functioning. Future
      directions for research and intervention are discussed.

PMID- 21878782
TI  - Telephone depression care management for Latino Medicaid health plan members: a
      pilot randomized controlled trial.
AB  - The objective of this pilot study was to provide a preliminary test of
      feasibility, acceptability, and efficacy of telephone depression care management
      among Latino Medicaid health plan members. Thirty-eight depressed primary care
      patients were enrolled in a pilot randomized trial of telephone depression care
      management + treatment as usual (TAU) versus TAU only. Bilingual care managers
      conducted care management for 3 months following an antidepressant prescription.
      For 1 year, research staff attempted to contact 929 potentially eligible members
      and enrolled 38. Qualitative analyses suggested that, of the participants we
      interviewed, most expressed satisfaction with the program. Participants suggested
      ways to improve recruitment, such as face-to-face contact. When compared with the
      group receiving TAU, there was a trend for the intervention group to experience
      less depression in time. This pilot study suggests that this program may be
      promising; however, there is need to investigate ways to better reach those who
      might find the program helpful.

PMID- 21878783
TI  - The effects of neuroticism, extraversion, and positive and negative life events
      on a one-year course of depressive symptoms in euthymic previously depressed
      patients versus healthy controls.
AB  - We investigated a) the concurrent impact of positive and negative life events on
      the course of depressive symptoms in persons remitted from depression and healthy
      controls, b) whether the impact of life events on symptom course is moderated by
      the history of depression and the personality traits of neuroticism and
      extraversion, and c) whether life events mediate possible relationships of
      history of depression and personality traits with symptom course. Using data from
      the Netherlands Study of Depression and Anxiety, we examined 239 euthymic
      participants with a previous depressive disorder based on DSM-IV and 450 healthy
      controls who completed a) baseline assessments of personality dimensions (NEO
      Five-Factor Inventory) and depression severity (Inventory of Depressive Symptoms
      [IDS]) and b) 1-year follow-up assessments of depression severity and the
      occurrence of positive and negative life events during the follow-up period (List
      of Threatening Events Questionnaire). Remitted persons reported higher IDS scores
      at 1-year follow-up than did the controls. Extraversion and positive and negative
      life events independently predicted the course of depressive symptoms. The impact
      of life events on symptom course was not moderated by history of depression or
      personality traits. The effect of extraversion on symptom course was partly
      caused by differential engagement in positive life events.

PMID- 21878784
TI  - Alexithymia in obsessive-compulsive disorder: clinical correlates and symptom
      dimensions.
AB  - Previous studies have indicated that obsessive-compulsive disorder (OCD) is
      associated with alexithymic traits. The purpose of the current study was to
      evaluate the difference of alexithymia in OCD patients and healthy controls. This
      study was also designed to elucidate a specific link between certain OCD symptom
      dimensions and alexithymia. Forty-five patients with OCD and 45 healthy controls
      completed measures of the OCD symptom severity, alexithymia, anxiety, and
      depression. Patients with OCD had significantly higher scores of alexithymia than
      did the healthy controls. Multiple regression analysis revealed that age at onset
      and the level of anxiety were significantly associated with alexithymia.
      "Sexual/religious obsessions" was the only symptom dimension that showed a
      positive association with alexithymia in OCD patients. These findings suggest
      that OCD patients with a high level of anxiety and an early age of onset may have
      greater alexithymic tendency. We also found the first evidence for a specific
      link between sexual/religious obsessions and alexithymia in patients with OCD.

PMID- 21878785
TI  - Selective attention in depression: influence of emotionality and personal
      relevance.
AB  - Selective attention to negative stimuli has been discussed as being an essential
      characteristic of depressive disorder. Theories and empirical data, however, are
      contradictory. The present study addressed the question of whether depressive
      patients selectively attend to negatively valenced and personally relevant or
      irrelevant stimuli and whether they habituate to these stimuli. Thirty-one
      inpatients with major depressive disorder and 37 healthy controls participated in
      the study. They underwent a modification of the emotional Stroop paradigm. The
      results indicated that personally relevant stimuli evoked more pronounced Stroop
      interference than did stimuli without personal relevance in all subjects.
      Furthermore, habituation to personally relevant negative stimuli was seen in both
      depressive patients and control subjects. The present findings question a
      generally negative attentional bias as being a specific characteristic of
      depressive disorder. Furthermore, as depressed patients habituated to personally
      relevant negative stimuli, exposure therapy might be suitable for the treatment
      of depressive disorder.

PMID- 21878786
TI  - The journey through cannabis use: a qualitative study of the experiences of young
      adults with psychosis.
AB  - The present study explored the personal experiences of cannabis and psychosis
      among young adults, including the reasons and meanings of cannabis use and the
      perceived relationship between cannabis and mental health. Interviews with seven
      young adults with psychosis who described regular current or past cannabis use
      were conducted and analyzed using Interpretative Phenomenological Analysis. Four
      master themes emerged: The Journey Through Cannabis Use, The Social and Cultural
      World, The Struggle to Make Sense, and The Depths and Beyond. Respondent
      validation supported these themes, particularly the idea of cannabis use as a
      journey that changed in time. Social and cultural factors clearly influenced the
      initiation of and decision whether to continue using cannabis. Individuals could
      simultaneously hold positive and negative views on using cannabis. Implications
      for clinical interventions are explored, and the relevance of motivational
      interviewing and the stages of change models of behavior change are noted.

PMID- 21878787
TI  - Auditory hallucinations and posttraumatic stress disorder within schizophrenia
      and substance abuse.
AB  - There is a high prevalence of traumatic events within individuals diagnosed with
      schizophrenia and of auditory hallucinations within individuals diagnosed with
      posttraumatic stress disorder (PTSD). However, the relationship among the
      symptoms associated with these disorders remains poorly understood. We conducted
      a multidimensional assessment of auditory hallucinations within a sample
      diagnosed with schizophrenia and substance abuse, both with and without comorbid
      PTSD. The results suggest a rate of comorbid PTSD similar to those reported in
      other studies. Patients who have comorbid PTSD reported more distressing auditory
      hallucinations. However, the hallucinations were not more frequent or of longer
      duration. The need for a multidimensional assessment is supported. The results
      are discussed within current theoretical accounts of traumatic psychosis.

PMID- 21878788
TI  - Change in defense mechanisms during short-term dynamic and cognitive therapy in
      patients with cluster C personality disorders.
AB  - The aims of this study were to examine whether a change in overall defensive
      functioning during treatment a) would predict change in symptom distress during
      the course of treatment and follow-up and b) would be greater in short-term
      dynamic therapy than in cognitive therapy. Patients (N = 50) who met criteria for
      cluster C personality disorders were randomized to 40 weekly sessions of short
      term dynamic therapy or cognitive therapy. Video recordings of a pretreatment
      interview and therapy session 36 were evaluated using the Defense Mechanisms
      Rating Scales. Symptom distress was measured using the revised version of Symptom
      Checklist-90. Change in overall defensive functioning during treatment predicted
      change in symptom distress from pretreatment to 2 years after treatment. Both
      treatment groups showed significant changes in defensive functioning toward
      greater adaptability but without any significant differences between the short
      term dynamic therapy and cognitive therapy groups in a sample of patients with
      cluster C personality disorders.

PMID- 21878789
TI  - Increased anger is associated with increased hemispheric asymmetry: support for
      anger-tympanic membrane relationships.
AB  - We recently reported that increased anger/hostility is associated with an
      increased imbalance of hemispheric activity, regardless of which particular
      hemisphere is more active (as indicated by increased absolute difference in
      temperature between the right and left tympanic membrane (ar-lTMT; Propper et
      al., J Nerv Ment Dis 198:691-694, 2010). In that study, we examined baseline
      levels of emotion and ar-lTMT; in this study, we used sustained unilateral gaze
      to manipulate hemispheric activity to further investigate the nature of the
      relationship between anger, ar-lTMT, and hemispheric imbalance. Both rightward
      (significantly) and leftward (modestly) sustained unilateral gaze increased
      anger, providing further evidence that anger is associated with the asymmetry of
      hemispheric activation. We also support our previous work demonstrating a
      relationship between increased anger and increased ar-lTMT. This is the second
      study supporting the use of ar-lTMT as a simple and convenient measure of
      hemispheric activation and as an objective correlate of anger.

PMID- 21878790
TI  - Visual mismatch negativity and its importance in visual cognitive sciences.
AB  - This review paper on visual mismatch negativity (MMN), an event-related brain
      potential component, provides arguments in favor of its theoretical importance in
      visual cognitive sciences. We propose that (a) previous visual MMN findings can
      be regarded as ample evidence for the existence of unintentional prediction about
      the next state of a visual object in the immediate future on the basis of its
      temporal context ('unintentional temporal-context-based prediction in vision');
      (b) such predictive processes may be qualitatively similar to those revealed by
      behavioral phenomena, such as representational momentum, flash-lag effect, and
      perceptual sequence learning; (c) such predictive processes may provide
      advantages for our adaptation to the visual environment at the computational,
      neural, and behavioral levels, and (d) in concert with such behavioral phenomena,
      visual MMN could be a unique and powerful tool for tapping into the predictive
      power of the human visual system.

PMID- 21878791
TI  - Neural correlates of sentence reading in children with reading difficulties.
AB  - In contrast to word-level skills, the neural basis of sentence comprehension in
      children with reading difficulties is not well understood. Using magnetic source
      imaging, we investigated the spatiotemporal dynamics of regional activity
      associated with silent passage reading in nonimpaired and students with reading
      difficulties. The latter exhibited underactivation of the temporoparietal and
      visual cortices, bilaterally, and of the left posterior cingulate region. Late
      activity in left temporoparietal and ventral occipitotemporal regions was found
      to be a significant predictor of individual reading ability in nonimpaired, but
      not in students with reading difficulties. These findings support the notion that
      reduced temporoparietal activation during word reading in context, is a hallmark
      of the functional deficit in reading disability.

PMID- 21878792
TI  - Neural basis of pleasant and unpleasant emotions induced by social reputation.
AB  - We used positron emission tomography to identify brain regions involved in the
      processing of emotions induced by social reputation from others. During positron
      emission tomographic scanning, individuals were presented with either a positive
      or a negative social reputation combined with face photographs of persons whom
      the individuals either liked or disliked. Behavioral results revealed that a
      positive reputation led to a higher pleasantness score than a negative
      reputation. Imaging data demonstrated that the orbitofrontal cortex was activated
      with positive reputations relative to negative reputations, and that the amygdala
      was activated with negative reputations relative to positive reputations. These
      findings suggest that pleasant and unpleasant emotions induced by positive and
      negative social reputations from others are associated with activity in different
      brain regions.

PMID- 21878793
TI  - A1 receptors inhibit glutamate release in rat medullary dorsal horn neurons.
AB  - We have investigated the adenosine-mediated presynaptic inhibition of primary
      afferent-evoked glutamate release in rat substantia gelatinosa neurons of the
      trigeminal subnucleus caudalis using a conventional whole-cell patch clamp
      technique. Adenosine reversibly and concentration dependently decreased the
      amplitude of glutamatergic excitatory postsynaptic currents and increased the
      paired-pulse ratio, indicating that adenosine acts presynaptically to reduce
      glutamate release from primary afferents. The adenosine-induced inhibition of
      excitatory postsynaptic currents was occluded by a selective A1 receptor
      antagonist, DPCPX, and was mimicked by a selective A1 receptor agonist CPA. The
      results suggest that presynaptic A1 receptors decrease action potential-dependent
      glutamate release from trigeminal primary afferents onto medullary dorsal horn
      neurons, and thus adenosine A1 receptors could be a potential target for the
      treatment of pain of orofacial tissues.

PMID- 21878794
TI  - Functional and molecular interactions between Rac1 and FE65.
AB  - FE65 is reported to act as an adaptor protein with several protein-interaction
      domains, including one WW domain and two phosphotyrosine interaction/binding
      domains. Through these binding domains, FE65 was considered to recruit various
      binding partners together to form functional complexes in a certain cellular
      compartment. In this study, we demonstrated that Rac1, a member of the Rho family
      GTPases, bound with FE65. We also elucidated that Rac1 inhibitor significantly
      suppressed FE65 expression, and Rac1 small interfering RNA transduction
      significantly decreased FE65 expression. FE65 small interfering RNA, however, did
      not influence Rac1 expression and its activity. Taken together, our results
      reveal that Rac1 interacts with FE65, and Rac1 activity regulates FE65
      expression.

PMID- 21878795
TI  - The last slice of cheese.

PMID- 21878796
TI  - An intervention fidelity framework for technology-based behavioral interventions.
AB  - BACKGROUND: Despite the proliferation of health technologies, descriptions of the
      unique considerations and practical guidance for evaluating the intervention
      fidelity of technology-based behavioral interventions are lacking. OBJECTIVES:
      The aims of this study were to (a) discuss how technology-based behavioral
      interventions challenge conventions about how intervention fidelity is
      conceptualized and evaluated, (b) propose an intervention fidelity framework that
      may be more appropriate for technology-based behavioral interventions, and (c)
      present a plan for operationalizing each concept in the framework using the
      intervention fidelity monitoring plan for Pocket PATH (Personal Assistant for
      Tracking Health), a mobile health technology designed to promote self-care
      behaviors after lung transplantation, as an exemplar. METHOD: The literature
      related to intervention fidelity and technology acceptance was used to identify
      the issues that are unique to the fidelity of technology-based behavioral
      interventions and thus important to include in a proposed intervention fidelity
      framework. An intervention fidelity monitoring plan for technology-based
      behavioral interventions was developed as an example. RESULTS: The intervention
      fidelity monitoring plan was deemed feasible and practical to implement and
      showed utility in operationalizing the concepts such as assessing
      interventionists' delivery and participants' acceptance of the technology-based
      behavioral intervention. DISCUSSION: The framework has the potential to guide the
      development of implementation fidelity monitoring tools for other technology
      based behavioral interventions. Further application and testing of this framework
      will allow for a better understanding of the role that technology acceptance
      plays in the adoption and enactment of the behaviors that technology-based
      behavioral interventions are intended to promote.

PMID- 21878797
TI  - Tailoring a treatment fidelity framework for an intensive care unit clinical
      trial.
AB  - BACKGROUND: Treatment fidelity (TF) refers to methodological strategies and
      practices used to monitor and enhance the reliability and validity of behavioral
      interventions. Treatment fidelity monitoring enhances internal and external
      validity and is needed for study replication and generalizability. OBJECTIVES:
      The aim of this study was to describe the implementation, monitoring, and impact
      of TF in an intensive-care-unit-based clinical trial testing music for anxiety
      self-management with mechanically ventilated patients. METHOD: Development of the
      criteria was based on the Five-Component Treatment Fidelity Framework from the
      Treatment Fidelity Workgroup. Descriptive statistics were used to evaluate
      adherence rates to the key TF criteria and the reasons criteria were unmet.
      Descriptive and nonparametric statistics were used to evaluate the impact of TF
      on participants' use of the assigned intervention. RESULTS: The Treatment
      Fidelity Framework was adapted easily to fit the study interventions. After the
      initial implementation phase of monitoring, adherence to key criteria was
      maintained at the targeted level of 80%. The majority of barriers to adherence
      affected the research nurses' opportunity to interact with the participant and
      encourage use of the intervention. There was a trend toward increased use of
      equipment associated with the assigned condition after the initiation of TF;
      however, this difference was not statistically significant. DISCUSSION: Treatment
      fidelity monitoring is an iterative process that requires ongoing vigilance.
      Identification of barriers and the implementation of methods to enhance protocol
      adherence are needed to enhance the reliability, validity, and generalizability
      of clinical trials in the dynamic and challenging research environment of the
      intensive care unit.

PMID- 21878798
TI  - Prevalence of limited health literacy and compensatory strategies used by
      hospitalized patients.
AB  - BACKGROUND: Limited health literacy is associated with higher rates of
      hospitalization. However, the prevalence and etiology of limited health literacy
      among hospitalized adults and the compensatory strategies used are not known.
      OBJECTIVES: The aims of this study were to determine the prevalence and
      demographic associations of limited health literacy in hospitalized patients and
      to identify the perceived etiology and use of any compensatory strategies.
      METHOD: A cross-sectional study was implemented of a consecutive sample of
      hospitalized adults admitted to the Internal Medicine Hospitalist Service at a
      440-bed academic medical center (n = 103) in Vermont. Health literacy was
      determined using the short form of the Test of Functional Health Literacy in
      Adults. Demographic data, perceived etiology of difficulties in reading or
      understanding health information, and use of compensatory strategies were self
      reported. RESULTS: Sixty percent of medical inpatients have limited health
      literacy. Thirty-six percent of patients with limited health literacy attribute
      this to difficulties with vision. Sixty-two percent of all medical inpatients
      rely on help from a health professional, and 23% look to a family member when
      faced with challenges in reading or understanding health information. DISCUSSION:
      The prevalence of limited health literacy is high in hospitalized medical
      patients. Further study of the timing and methods of communicating information to
      hospitalized patients is warranted. Assuring that the patient and/or family
      understand the postdischarge plans will be an important step to improving quality
      and safety.

PMID- 21878799
TI  - Endophthalmitis in microincision vitrectomy: outcomes of gas-filled eyes.
AB  - PURPOSE: To assess whether performing an air or gas exchange at the conclusion of
      a microincision vitrectomy procedure is beneficial regarding the rate of
      endophthalmitis. METHODS: This was a collaborative, multicenter, retrospective
      chart review of 2,336 eyes that underwent microincision sutureless vitrectomy (23
      or 25 gauge) with either SF6 or C3F8 gas endotamponade for macular hole between
      January 2008 and December 2009. For all eyes, the search methodology was
      structured to identify the main outcome measure, which was the occurrence of
      acute postoperative endophthalmitis (<6 weeks after pars plana vitrectomy).
      RESULTS: Of the cumulative 2,336 consecutive cases over a 2-year period, only 1
      (0.04%) had postoperative endophthalmitis. All eyes had near-complete gas-fluid
      exchange at the end of surgery; C3F8 was the most common endotamponade agent. The
      majority of cases were performed with 23-gauge vitrectomy. No other complications
      were noted. CONCLUSION: Endophthalmitis was a rare occurrence in this large
      series of gas-filled eyes after macular hole surgery (0.04%). Gas endotamponade
      after microincision sutureless vitrectomy may be beneficial in reducing the risk
      of postoperative endophthalmitis; however, additional studies are necessary to
      make a definitive recommendation.

PMID- 21878800
TI  - Endophthalmitis after intravitreal injection: the importance of viridans
      streptococci.
AB  - PURPOSE: To determine the rate of postinjection endophthalmitis and compare
      microbial etiology and outcomes in office-based injection-related endophthalmitis
      versus those acquired after operating room procedures. METHODS: Retrospective,
      observational case series. Consecutive cases of endophthalmitis seen at Retina
      Consultants of Houston between July 2000 and July 2010 were classified as
      postsurgical or post-intravitreal injection. Cases secondary to glaucoma surgery,
      trauma, and endogenous sources were excluded. Main study measures were incidence
      of endophthalmitis, microbiology results, and visual outcomes. RESULTS: In all,
      109 cases of endophthalmitis were identified: 88 postsurgical and 21 post
      intravitreal injection (3 from clinical trials and 5 from outside
      ophthalmologists). A total of 33,580 intravitreal injections were performed at
      Retina Consultants of Houston (endophthalmitis rate = 0.04%, 13 of 33,580; 95%
      confidence interval, 0.02-0.07%). The most common organisms isolated overall were
      coagulase-negative staphylococci, while viridans streptococci, a component of
      human oral flora, was identified over three times more often in the postinjection
      group compared with the postsurgical group. Compared with all other culture
      positive cases related to intravitreal injection, postinjection endophthalmitis
      secondary to viridans streptococci presented much more rapidly (P < 0.001) and
      final visual outcomes were much worse (P = 0.004) CONCLUSION: Although the
      overall risk of postinjection endophthalmitis is low, viridans streptococci were
      identified over three times more frequently in postinjection cases compared with
      postsurgical cases and these cases had much worse clinical outcomes. The office
      based setting for intravitreal injections may lead to a higher risk for infection
      from oral pathogens.

PMID- 21878801
TI  - Fluorescein staining of the vitreous during vitrectomy for retinopathy of
      prematurity.

PMID- 21878802
TI  - Morphologic and functional advantages of macular hole surgery with brilliant blue
      G-assisted internal limiting membrane peeling.

PMID- 21878803
TI  - Sildenafil citrate and choroidal thickness.

PMID- 21878804
TI  - Three-week nutritional supplementation effect on long-term nutritional status of
      patients with mild Alzheimer disease.
AB  - Short-term nutritional supplements enable an improvement in Alzheimer patients'
      nutritional status, but it remains to be seen whether they will be sufficient to
      improve long-term nutritional status. The aim of this study was to evaluate the
      long-term impact of a 3-week nutritional supplementation on the nutritional
      status of undernourished patients with probable mild Alzheimer disease. A 21-day
      prospective randomized nonblinded controlled trial was conducted. Patients were
      followed-up for an additional period until the 90th day after the beginning of
      the intervention. Intervention resulted in significant improvements in Mini
      Nutritional Assessment (MNA) score [Mean=1.4, standard deviation (SD)=0.8 vs. 0.0
      (0.1) in the control group, P<0.001] and also in anthropometrical and serum
      biomarkers of Alzheimer disease (AD) patients' nutritional status. Further
      improvements in the AD patients' MNA mean score=1.4 (SD=2.3) versus -0.5 (SD=0.6)
      in the control group (P=0.003) were seen at 90 days follow-up. Data show that a 3
      week nutritional supplementation has a positive long-term impact on the
      nutritional status of undernourished patients with mild probable AD.

PMID- 21878805
TI  - Serotonergic function and treatment of behavioral and psychological symptoms of
      frontotemporal dementia.
AB  - OBJECTIVES: The purposes of this study were first, to evaluate the effectiveness
      of citalopram in treating behavioral disturbances in frontotemporal dementia
      (FTD) subjects and second, to determine whether an association exists between
      serotonergic function, as determined by a neuroendocrine challenge, and treatment
      response. DESIGN: Single-dose citalopram (30 mg per os) challenge followed by a 6
      week open-label study. SETTING: Outpatients referred to memory clinics.
      PARTICIPANTS: Fifteen patients suffering from FTD with severe behavioral and
      psychological symptoms of dementia. INTERVENTION: Following citalopram challenge,
      all patients were treated with citalopram titrated to a target dose of 40 mg once
      daily. MEASUREMENTS: Behavioral disturbances, using the Neuropsychiatric
      Inventory (NPI) (primary outcome) and Frontal Behavioural Inventory (secondary
      outcome), were assessed. Change in prolactin concentration following citalopram
      challenge was used as an index of central serotonergic response. RESULTS:
      Citalopram treatment was effective in treating behavioral symptoms, with
      significant decreases in NPI total score (F[2, 28] = 6.644, p = 0.004),
      disinhibition (F[2, 28] = 4.030, p = 0.029), irritability (F[2, 28] = 7.497, p =
      0.003) and depression (F[2, 28] = 3.467, p = 0.045) scores over the 6 weeks.
      Significant improvement in Frontal Behavioural Inventory scores suggested that
      citalopram was also effective in the treatment ofbehaviors specific to FTD. A
      lower change score in concentration of prolactin was significantly positively
      correlated with greater improvement in the total NPI score from baseline to
      endpoint (r = 0.687, p = 0.005). A blunted response to a citalopram challenge,
      implying a dysfunctional serotonergic system, predicted a more positive treatment
      outcome. CONCLUSIONS: The results suggest that despite the endogenous serotonin
      deficiency of FTD, citalopram treatment may be effective in targeting the
      behavioral disturbances characteristic of FTD.

PMID- 21878807
TI  - Nonanesthetic malignant hyperthermia.

PMID- 21878808
TI  - Case scenario:  anesthetic considerations for thoracoabdominal aortic aneurysm
      repair.

PMID- 21878809
TI  - To live a story.

PMID- 21878810
TI  - Offset analgesia in neuropathic pain patients and effect of treatment with
      morphine and ketamine.
AB  - BACKGROUND: Offset analgesia, in which a disproportionally large amount of
      analgesia becomes apparent upon a slight decrease in noxious heat stimulation,
      has not been described previously in patients with chronic pain. METHODS: Offset
      analgesia responses in 10 patients with neuropathic pain (in both legs) were
      compared with 10 matched healthy controls and volunteers from a convenience
      sample (n = 110) with an age range of 6-80 yr. Offset analgesia was defined by
      the reduction in electronic pain score upon the 1 degrees C decrease in noxious
      heat stimulus relative to the peak pain score where pain was administered at the
      volar side of the arm. RESULTS: Offset analgesia was present in healthy
      volunteers irrespective of age and sex (pain score decrease = 97 +/- 1% [mean +/-
      SEM]). In contrast, a reduced or absent offset analgesia response was observed in
      patients with neuropathic pain (pain score decrease = 56 +/- 9% vs. controls 98
      +/- 1%, P < 0.001). Intravenous treatment with ketamine, morphine, and placebo
      had no effect on offset analgesia in patients, despite sharp reductions in
      spontaneous pain scores. CONCLUSIONS: These data indicate that offset analgesia
      is fully developed at the age of 6 yr and does not undergo additional maturation.
      The reduced or absent responses observed in patients with chronic neuropathic
      pain indicate the inability to modulate changes in pain stimulation, with
      perseverance of pain perception in situations in which healthy subjects display
      signs of strong analgesia. Both central and peripheral sites may be involved in
      the altered offset analgesia responses in these patients.

PMID- 21878811
TI  - Evaluating bowel cleansing method for rectal cancer surgery.

PMID- 21878812
TI  - Malnutrition and postoperative complications in abdominal surgery.

PMID- 21878813
TI  - Glycogen synthase kinase 3beta inhibitors induce apoptosis in ovarian cancer
      cells and inhibit in-vivo tumor growth.
AB  - Ovarian cancer is the most lethal gynecological malignancy among US women.
      Paclitaxel/carboplatin is the current drug therapy used to treat ovarian cancer,
      but most women develop drug resistance and recurrence of the disease,
      necessitating alternative strategies for treatment. A possible molecular target
      for cancer therapy is glycogen synthase kinase 3beta (GSK3beta), a downstream
      kinase in the Wnt signaling pathway that is overexpressed in serous ovarian
      cancer. Novel maleimide-based GSK3beta inhibitors (GSK3betai) were synthesized,
      selected, and tested in vitro using SKOV3 and OVCA432 serous ovarian cancer cell
      lines. From a panel of 10 inhibitors, GSK3betai 9ING41 was found to be the most
      effective in vitro. 9ING41 induced apoptosis as indicated by 4',6-diamidino-2
      phenylindole-positive nuclear condensation, poly (ADP-ribose) polymerase
      cleavage, and terminal deoxynucleotidyl transferase dUTP nick end labeling
      staining. The mechanism for apoptosis was through caspase-3 cleavage. GSK3betai
      upregulated phosphorylation of the inhibitory serine residue of GSK3beta in
      OVCA432 and SKOV3 cell lines and also inhibited phosphorylation of the downstream
      target glycogen synthase. An in-vivo xenograft study using SKOV3 cells
      demonstrated that tumor progression was hindered by 9ING41 in vivo. The maximum
      tolerated dose for 9ING41 was greater than 500 mg/kg in rats. Pharmacokinetic
      analysis showed 9ING41 to have a bioavailability of 4.5% and to be well
      distributed in tissues. Therefore, GSK3beta inhibitors alone or in combination
      with existing drugs may hinder the growth of serous ovarian cancers.

PMID- 21878814
TI  - Transmissibility of seasonal and pandemic influenza in a cohort of households in
      Hong Kong in 2009.
AB  - BACKGROUND: The household secondary attack proportion (SAP) is commonly used to
      measure the transmissibility of an infectious disease. METHODS: We analyzed the
      final outbreak size distributions of pandemic A(H1N1), seasonal A(H1N1), and
      A(H3N2) infections identified in paired sera collected from members of 117 Hong
      Kong households in April and in August-October 2009. RESULTS: The estimated
      community probability of infection overall was higher for children than adults;
      the probability was similar for pandemic A(H1N1) and seasonal A(H3N2) influenza.
      The household SAP for pandemic A(H1N1) was higher in children than in adults,
      whereas for seasonal A(H3N2), it was similar in children and adults. The
      estimated SAPs were similar for seasonal A(H3N2) and pandemic A(H1N1) after
      excluding persons with higher baseline antibody titers from analysis.
      CONCLUSIONS: Pandemic and seasonal influenza A viruses had similar age-specific
      transmissibility in a cohort of initially uninfected households, after adjustment
      for baseline immunity.

PMID- 21878815
TI  - How much are we missing in SNP-by-SNP analyses of genome-wide association
      studies?
AB  - Genome-wide association studies have discovered common genetic variants
      associated with susceptibility for several complex diseases, but they have been
      unfruitful for many others. Typically, analysis is done "agnostically," by
      considering one single nucleotide polymorphism (SNP) at a time and controlling
      the overall type I error rate by correcting for multiple testing. Such one-at-a
      time analyses may be inadequate for screening genes under realistic causal
      models. We use oral clefting as a disease model to develop a range of toy example
      scenarios: risk might involve only genes, or genes and exposure, or genes,
      exposure, and their supermultiplicative interaction. These examples illustrate
      how dramatically important genetic variants can be obscured by a one-SNP-at-a
      time analysis when multiple biologic pathways and multiple genes jointly
      influence etiology. These examples highlight the need for better methods for gene
      by-environment and gene-by-gene analyses.

PMID- 21878816
TI  - Needling augmented with topical application of mitomycin C for management of bleb
      failure.
AB  - PURPOSE: To study the effect of topical application of mitomycin C on enhancing
      the efficacy of needling in the management of bleb failure. PATIENTS AND METHODS:
      Thirty-six eyes of 32 consecutive patients with an intraocular pressure over 21
      mmHg, without bleb or with a thick, flat bleb after the second postoperative
      month after trabeculectomy, were included in the study. Needling with mitomycin C
      was performed in the other 18 eyes with bleb failure (group A) and needling
      without antimetabolite was performed in 18 eyes (group B). Topical application of
      mitomycin C (0.4 mg/mL) with a microsponge over the conjunctiva at the failed
      bleb for 5 minutes (group A) was performed; after irrigation, the needling
      procedure was the same in both groups. A 30-gauge needle was used to perforate
      the area of subconjunctival and subscleral fibrosis and to reestablish flow;
      conjunctival puncture was at least 7 mm away from the bleb and no sutures were
      taken after needling. Follow-up was performed for 1 year after needling. RESULTS:
      Overall, 55 needling procedures were performed; needling was done twice in 17
      eyes in group B, whereas only 2 eyes needed more than 1 needling procedure in
      group A. The difference was statistically highly significant, and the mean follow
      up was 8.9 +/- 3.7 months. Mean intraocular pressure was 28.9 +/- 4.2 mm Hg and
      27.8 +/- 4.7 mm Hg in group A and group B respectively before any intervention;
      this decreased to a mean of 19.8 +/- 2.7 mm Hg and 20.5 +/- 4.8 mm Hg
      respectively without medication after 6 months of last needling. Complications
      included diffuse corneal punctate epitheliopathy lasting for 2 to 3 weeks (2 eyes
      in group A), subconjunctival hemorrhage (3 eyes in each group), and hyphema (2
      eyes in each group). CONCLUSIONS: Topical application of mitomycin C with needle
      revision seems to be an extremely effective way to revive failed filtration
      surgery. The incidence of complications related to mitomycin C was minimal.

PMID- 21878817
TI  - Comparison of visual field severity classification systems for glaucoma.
AB  - PURPOSE: To compare categorical severity classification systems for glaucoma.
      METHODS: This cross-sectional study included 1,921 eyes (49.5% right eye) from
      1,137 participants from the Diagnostic Innovations in Glaucoma Study and African
      Descent and Glaucoma Evaluation Study. Standard automated perimetry fields were
      classified using the: (1) Advanced Glaucoma Intervention Study scoring system
      (AGIS), (2) Glaucoma Severity Staging system (GSS), and (3) Enhanced Glaucoma
      Severity Staging system (eGSS). Systems were characterized using the following
      continuous measures of severity: mean deviation, pattern standard deviation, and
      visual field index. Classifications between systems and with optic disc
      stereophotograph assessment were compared (kappa) and some stages were
      consolidated to evaluate severity classification across systems (Wilcoxon test).
      RESULTS: Mean deviation, pattern standard deviation, and visual field index were
      significantly different between GSS and AGIS, and GSS and eGSS in normal and
      abnormal fields (P<0.005). Agreement between AGIS and eGSS was substantial
      (kappa=0.715+/-0.012); agreement between GSS and eGSS (kappa=0.559+/-0.014) and
      AGIS (kappa=0.519+/-0.016) was moderate. eGSS tended to stage abnormal fields
      most severely followed by GSS and then AGIS (P<0.001). CONCLUSIONS: The presence
      of glaucomatous optic neuropathy increases with staging severity for all systems.
      However, different systems led to different severity staging. Of the systems
      examined in this study, eGSS may be the better choice for its ease of use for
      both clinicians and researchers.

PMID- 21878818
TI  - Outcomes of fornix-based versus limbus-based conjunctival incisions for glaucoma
      drainage device implant.
AB  - PURPOSE: To determine the effect of conjunctival incision location on the long
      term efficacy of nonvalved glaucoma drainage devices. MATERIALS AND METHODS: We
      conducted a retrospective review of patients >=18 years of age with uncontrolled
      glaucoma [intraocular pressure (IOP) >=18 mm Hg] who underwent glaucoma drainage
      device implantation. A comparison was made of a limbal-based (LB-BGI) versus
      fornix-based (FB-BGI) conjunctival flap during placement of a 350-mm Baerveldt
      glaucoma implant (AMO, Santa Ana, CA) in subjects with at least 1 year of follow
      up data. The primary outcome measure was IOP; secondary outcome measures were
      medication burden, visual acuity, and surgical complications. RESULTS: One
      hundred sixty eyes of 147 glaucoma patients were included. Two years after
      surgery, the IOP in the LB-BGI group was 14.3+/-5.3 mm Hg and in the FB-BGI group
      13.1+/-4.7 mm Hg (P=0.47). Overall success of IOP control was achieved at the
      final visit (range 1 to 5 y) in 90% of the LB-BGI group and 87% of the FB-BGI
      group (P=0.63). The medication burden of the 2 groups at 1 and 2 years after
      surgery was not statistically significantly different. Worsening of visual acuity
      by more than 2 lines was not statistically different between the groups 2 years
      after the surgery and at the final visit (P=0.47, P=0.60, respectively). A
      greater number of eyes developed endophthalmitis and were more likely to undergo
      subsequent tube revision in the FB-BGI group, but the differences were not
      significant. CONCLUSIONS: Both incision techniques were equally effective in
      controlling IOP. Each surgical approach has its advantages and this study
      suggests that either technique may be used safely and effectively.

PMID- 21878819
TI  - Can intraocular pressure asymmetry indicate undiagnosed primary glaucoma? The
      Chennai Glaucoma Study.
AB  - AIM: : To investigate the association of intraocular pressure (IOP) asymmetry
      with undiagnosed primary glaucoma in rural and urban populations of south India.
      METHODS: Chennai Glaucoma Study is a population-based cross-sectional study. The
      participants were adults, 40 years or older. The prevalence of primary glaucoma
      was defined using International Society of Geographical and Epidemiological
      Ophthalmology classification. IOP asymmetry was diagnosed when the difference in
      IOP between 2 eyes was >3 mm Hg. Analysis included only bilaterally phakic
      subjects. We excluded subjects with known glaucoma, secondary glaucoma,
      pseudoexfoliation, ocular trauma, and ocular surgery. RESULTS: Of 6310 subjects,
      3052 (48.4%) were rural residents. The mean age was 52 (standard deviation: 9.5)
      years. The prevalence of IOP asymmetry increased steadily with increasing patient
      age. The prevalence of undiagnosed primary glaucoma was 3.4% (95% confidence
      interval, 2.9-3.8). Undiagnosed primary glaucoma was 3 times more common in
      subjects with IOP asymmetry than without (odds ratio 3.08, 95% confidence
      interval, 2.1-4.3). The specificity of IOP asymmetry in detecting undiagnosed
      primary glaucoma was 92%. CONCLUSIONS: IOP asymmetry of >3 mm Hg has limited
      accuracy for the detection of undiagnosed primary glaucoma. The criterion should
      be combined with other indicators of glaucoma to build the pretest probability of
      the disease.

PMID- 21878820
TI  - Macular retinal thickness in glaucoma with superior or inferior visual hemifield
      defects.
AB  - PURPOSE: To elucidate the relationship between macular retinal thickness and
      corresponding superior or inferior visual hemifield defects in glaucoma patients.
      METHODS: Thirty-nine eyes of 39 patients with open-angle glaucoma showed superior
      or inferior hemifield defects (superior hemifield defects, 27 eyes; inferior
      hemifield defects, 12 eyes). We measured the retinal thickness of the parafovea
      and fovea centralis corresponding to a defect or an apparently normal hemifield
      by spectral domain optical coherence tomography. We then analyzed the
      relationship between the retinal thickness corresponding to an apparently normal
      hemifield and the severity of the glaucomatous visual field defect on the other
      side of the same eye. RESULTS: We found that the retinal thickness of the
      parafovea and fovea centralis significantly decreased, as the hemifield defect
      increased. The retinal thickness of the parafovea, the inner sector, outer
      sector, and inner and outer sectors, corresponding to the apparently normal
      hemifields significantly decreased with the progression of the hemifield defect
      on the other side. The mean+/-SD age of patients was 66.5+/-9.1 years and the
      refraction was -1.3+/-2.4 D. CONCLUSIONS: Macular retinal thickness decreases
      with a corresponding visual hemifield defect in glaucoma patients. Retinal
      structural changes precede the loss of the visual field in the apparently normal
      side.

PMID- 21878821
TI  - Periodic unilateral eyelid retraction in a pediatric patient.
AB  - A healthy 11-year-old girl presented with right upper eyelid retraction since
      birth. An evaluation including thyroid function studies and neuroimaging was
      negative, and the patient was scheduled for a right levator recession to address
      the eyelid malposition. Intraoperatively, after the induction of inhalational
      general anesthesia, the patient displayed cyclic right upper eyelid retraction.
      Occurring in intervals of exactly 48 seconds, these cycles involved a rapid
      elevation of the right eyelid from a position of half-closure to a retracted
      position just above the superior limbus. There was no change in pupil size or eye
      position during these cyclic spasms, and the contralateral eyelid was unaffected.
      The patient underwent an uncomplicated levator recession, which improved the
      upper eyelid retraction. Postoperative testing, including external motility video
      and infrared pupillometry, demonstrated no cyclic variation in eyelid position,
      eye position, or pupil size in the waking state. This is a unique case of
      unilateral eyelid retraction with periodic spasms under conditions of anesthesia
      without a preexisting oculomotor paresis; it represents an unusual variation on
      congenital eyelid retraction and classically described cyclic oculomotor palsy.

PMID- 21878822
TI  - Factors that differentiate acceleration ability in field sport athletes.
AB  - Speed and acceleration are essential for field sport athletes. However, the
      mechanical factors important for field sport acceleration have not been
      established in the scientific literature. The purpose of this study was to
      determine the biomechanical and performance factors that differentiate sprint
      acceleration ability in field sport athletes. Twenty men completed sprint tests
      for biomechanical analysis and tests of power, strength, and leg stiffness. The
      sprint intervals analyzed were 0-5, 5-10, and 0-10 m. The subjects were split
      into a faster and slower group based on 0- to 10-m velocity. A 1-way analysis of
      variance determined variables that significantly (p <= 0.05) distinguished
      between faster and slower acceleration. All subject data were then pooled for a
      correlation analysis to determine factors contributing most to acceleration. The
      results showed that 0- to 5-m (~16% difference) and 0- to 10-m (~11% difference)
      contact times for the faster group were significantly lower. Times to peak
      vertical and horizontal force during ground contact were lower for the faster
      group. This was associated with the reduced support times achieved by faster
      accelerators and their ability to generate force quickly. Ground contact force
      profiles during initial acceleration are useful discriminators of sprint
      performance in field sport athletes. For the strength and power measures, the
      faster group demonstrated a 14% greater countermovement jump and 48% greater
      reactive strength index. Significant correlations were found between velocity (0
      5, 5-10, and 0-10 m) and most strength and power measures. The novel finding of
      this study is that training programs directed toward improving field sport sprint
      acceleration should aim to reduce contact time and improve ground force
      efficiency. It is important that even during the short sprints required for field
      sports, practitioners focus on good technique with short contact times.

PMID- 21878823
TI  - Improving the Q:H strength ratio in women using plyometric exercises.
AB  - Plyometric training programs have been implemented in anterior cruciate ligament
      injury prevention programs. Plyometric exercises are designed to aid in the
      improvement of muscle strength and neuromuscular control. Our purpose was to
      examine the effects of plyometric training on lower leg strength in women. Thirty
      (age = 20.3 +/- 1.9 years) recreationally active women were divided into control
      and experimental groups. The experimental group performed a plyometric training
      program for 6 weeks, 3 d.wk(-1). All subjects attended 4 testing sessions: before
      the start of the training program and after weeks 2, 4, and 6. Concentric
      quadriceps and hamstring strength (dominant leg) was assessed using an isokinetic
      dynamometer at speeds of 60 and 120 degrees .s(-1). Peak torque, average peak
      torque, and average power (AvgPower) were measured. The results revealed a
      significant (p < 0.05) interaction between time and group for flexion PkTq and
      AvgPower at 120 degrees .s(-1). Post hoc analysis further revealed that PkTq at
      120 degrees .s(-1) was greater in the plyometric group than in the control group
      at testing session 4 and that AvgPower was greater in the plyometric group than
      in the control group in testing sessions 2-4. Our results indicate that the
      plyometric training program increased hamstring strength while maintaining
      quadriceps strength, thereby improving the Q:H strength ratio.

PMID- 21878824
TI  - Excess postexercise oxygen consumption is unaffected by the resistance and
      aerobic exercise order in an exercise session.
AB  - The main purpose of this study was to compare the magnitude and duration of
      excess postexercise oxygen consumption (EPOC) after 2 exercise sessions with
      different exercise mode orders, resistance followed by aerobic exercise (R-A);
      aerobic by resistance exercise (A-R). Seven young men (19.6 +/- 1.4 years)
      randomly underwent the 2 sessions. Aerobic exercise was performed on a treadmill
      for 30 minutes (80-85% of reserve heart rate). Resistance exercise consisted of 3
      sets of 10 repetition maximum on 5 exercises. Previous to the exercise sessions,
      V(O2), heart rate, V(CO2), and respiratory exchange rate (RER) were measured for
      15 minutes and again during recovery from exercise for 60 minutes. The EPOC
      magnitude was not significantly different between R-A (5.17 +/- 2.26 L) and A-R
      (5.23 +/- 2.48 L). Throughout the recovery period (60 minutes), V(O2) and HR
      values were significantly higher than those observed in the pre-exercise period
      (p < 0.05) in both exercise sessions. In the first 10 minutes of recovery, V(CO2)
      and RER declined to pre-exercise levels. Moreover, V(CO2) and RER values in A-R
      were significantly lower than in R-A. In conclusion, the main result of this
      study suggests that exercise mode order does not affect the EPOC magnitude and
      duration. Therefore, it is not necessary for an individual to consider the EPOC
      when making the decision as to which exercise mode is better to start a training
      session.

PMID- 21878825
TI  - Hypoglycemia after accidental pediatric sulfonylurea ingestions.
AB  - BACKGROUND: Because the prevalence of type 2 diabetes increases annually, there
      has been an increase in pediatric exposures to sulfonylureas. These medications
      are associated with delayed and often prolonged hypoglycemia. As such, most
      authorities but not all recommend admission for all pediatric patients with an
      accidental sulfonylurea ingestion. METHODS: This study is a retrospective chart
      review of all pediatric patients with sulfonylurea exposures admitted for 9 years
      at an urban, pediatric teaching hospital. The incidence and characteristics of
      the hypoglycemia were recorded and analyzed. RESULTS: During this time span, 93
      patients with accidental sulfonylurea exposures were admitted, with a median age
      of 1.83 years. Glyburide and glipizide accounted for most sulfonylureas.
      Hypoglycemia (blood glucose level <50 mg/dL) developed in 25 (58.1%) of 43
      patients who ingested glipizide, compared with 10 (25.6%) of 39 patients who
      ingested glyburide. The overall incidence of hypoglycemia was 44%. Hypoglycemia
      was more likely to occur with glipizide ingestion than glyburide (odds ratio,
      3.89 [95% confidence interval, 1.51-9.98]). No patient with a known time of
      ingestion developed hypoglycemia after 13 hours. CONCLUSIONS: Hypoglycemia is
      common after accidental sulfonylurea exposures. The results of this study support
      mandatory admission to a monitored setting for at least 16 hours, with frequent
      glucose determinations.

PMID- 21878826
TI  - Screening for postpartum depression in a pediatric emergency department.
AB  - OBJECTIVE: The objective was to determine whether a 3-question version of the
      Edinburgh Postpartum Depression Scale (EPDS) performs as well as the full EPDS in
      screening for postpartum depression in a pediatric emergency department (PED).
      METHODS: Mothers of infants younger than 6 months presenting to an urban PED were
      enrolled. After the PED encounter, mothers were asked about demographics, health
      problems, insurance status, social support, food and housing security, and 3
      questions from the EPDS. Mothers then completed the full EPDS. The primary
      outcome was the score on the full EPDS. Agreement between the 3 questions and the
      full EPDS for screening positive was measured. Test performance characteristics
      for screening positive with the 3 questions were calculated. Logistic regression
      determined the association between sociodemographic characteristics and screening
      positive. Provider impression of maternal depressive symptoms was recorded.
      RESULTS: Of 195 mothers enrolled, 23% screened positive using the EPDS; 34%
      screened positive using the 3 questions (kappa = 0.74). Compared with the EPDS,
      sensitivity of the 3 questions was 100%. Number of children younger than 5 years
      at home and having food and housing concerns were associated with screening
      positive. Of 44 mothers who screened positive on the full EPDS, providers
      identified 14 (32%) as having depressive symptoms or possibly being depressed.
      CONCLUSIONS: Three questions from the EPDS performed similarly to the full EPDS
      in screening for postpartum depressive symptoms in a PED. Future studies are
      needed to confirm these findings and examine whether screening improves maternal
      and child health outcomes and quality-of-life concerns.

PMID- 21878827
TI  - Subdural hematomas and emergency management in infancy and childhood: a single
      institution's experience.
AB  - OBJECTIVE: We aimed to identify the incidence, clinical features, management, and
      outcome of subdural hematomas (SHs) in infancy and childhood. METHODS: Twenty-one
      children younger than 11 years with SH were analyzed. Clinical features and
      possible child abuse were considered in each case. RESULTS: Eight children
      experienced minor injuries due to hitting of solid items on their head. Five of
      these children also had coagulation disorders. Three of the children suffered
      from child abuse, only one of the children had head trauma due to car accident.
      Nine of the patients experienced SH due to fall down. Nine patients have acute
      SH, 7 had subacute SH, 4 had chronic SH, and 1 had acute and subacute SH
      together. Clinical presentation varied greatly. Most of them presented with
      vomiting and seizure. The outcome patterns were different among the patients.
      Deep coma on admission was associated with an unfavorable outcome. CONCLUSIONS:
      Subdural hematoma is common in infancy and childhood and carries a poor
      prognosis. Most of the cases are due to head trauma, coagulation disorders, and
      child abuse. We believe that clinical investigation of such children should be
      carried out in a multidisciplinary approach with the collaboration of
      pediatricians, social workers, and neurosurgeons.

PMID- 21878828
TI  - Physicians' perceptions of background noise in a pediatric emergency department.
AB  - OBJECTIVE: The objectives of this study were to measure noise levels in a
      tertiary care pediatric emergency department (ED) and to identify attending staff
      physicians' and first-year residents' perceptions of background noise levels and
      its impact on communication and teaching. METHODS: A mixed methodology was used
      in this study. A sound level meter measuring 30 to 140 dB was placed in the ED
      for a week. All consenting staff physicians and first-year residents were
      surveyed using a semistructured questionnaire during the study period to assess
      their perceptions of background noise and its impact. Descriptive statistics were
      used for quantitative analysis. Narrative answers were coded and analyzed using
      the method of meaning condensation to assess the impact of background noise on
      both communication and teaching. RESULTS: The average noise level in the ED is
      68.73 dB for a 24-hour period. The number sound peaks higher than 80 dB, with an
      average of 309 dB/d (minimum, 193 dB; maximum, 461 dB). Only 35% of staff
      physicians' surveys and 22% of residents' surveys identified the noise levels to
      be uncomfortable. However, background noise in the ED was perceived as stressful,
      affecting interaction, communication, and teaching between residents and staff
      physicians. Staff physicians and residents stated that they feel helpless when it
      is too noisy and did not have good strategies to reduce background noise in the
      ED. CONCLUSIONS: The high background noise levels in a pediatric ED are perceived
      as stressful and interfering with communication and teaching. Noise levels in EDs
      should be measured, and noise reduction strategies should be implemented because
      physicians are not consistent in identifying excessive noise levels.

PMID- 21878829
TI  - Beliefs and practices of pediatric emergency physicians and nurses regarding
      counseling alcohol-using adolescents: can counseling practice be predicted?
AB  - OBJECTIVES: The objectives of the study were to investigate the attitudes and
      practices of pediatric emergency department (PED) physicians (MDs), MD extenders
      (MD's assistants [PAs], nurse practitioners [NPs]), and nurses (RNs) regarding
      their counseling of alcohol-using adolescent PED patients and to determine which,
      if any, PED clinician characteristics predict current counseling practice.
      METHODS: An Internet-based survey of PED clinicians (MDs, PAs, NPs, and RNs) from
      11 academic US PEDs was conducted. Respondents were asked about their counseling
      training, current counseling practices, confidence in their counseling skills,
      importance of counseling, attitudes and beliefs about counseling, and demographic
      information. Univariate and multivariate analyses were performed to determine the
      relationship between clinician characteristics and counseling practice. RESULTS:
      Counseling practice was strongly associated with one's profession; PED
      MDs/PAs/NPs reported significantly higher rates of counseling alcohol-using
      adolescents than PED RNs. These 2 groups differed significantly in terms of
      counseling training and experience. Counseling training and experience remained
      significant predictors of counseling practice, even after controlling for
      profession and other covariates. Both groups had similar views on the importance
      of counseling, confidence in their ability to counsel, and counseling substance
      using adolescent PED patients. CONCLUSIONS: Pediatric ED MDs/PAs/NPs differ
      significantly from PED RNs in their counseling training, experience, and
      practice. These findings have important implications for the training and support
      necessary to successfully implement PED counseling. Specifically, formal training
      in counseling during professional schooling and garnering counseling experience
      after completing training may be critical factors in promoting PED counseling.

PMID- 21878830
TI  - Children admitted to the hospital after returning to the emergency department
      within 72 hours.
AB  - OBJECTIVES: Children returning to the emergency department (ED) within 72 hours
      of their visit may increase overcrowding and health care costs. Identifying the
      characteristics of returning children who need admission may help distinguish who
      might need admission on their first visit. The objective of this study was to
      compare the characteristics of children who returned to the ED and needed
      admission to the characteristics of those discharged. METHODS: The study used a
      retrospective chart review of patients 19 years and younger visiting a tertiary
      pediatric ED during a 1-year period. We excluded patients who left without being
      seen and those leaving against medical advice. We determined the rate of return
      visits and then performed chi2 and Student t test analyses. Main outcome measures
      were return and subsequent hospital admission rate to the ED. RESULTS: Of 47,655
      eligible children, 2115 (4.4%) returned to the ED within 72 hours. The admission
      rate for the second visit was 353 (16.7%). There was no significant difference in
      age, sex, language spoken at home, or time elapsing from the first visit to the
      re-presentation to the ED between children who needed admission on the returned
      visit and those discharged when returning. The acuity was significantly lower
      among children discharged after returning (P < 0.001) but not among those
      admitted (P < 0.22). CONCLUSIONS: More than 4% of our pediatric ED visits are for
      children returning within 72 hours. Progression of illness resulting in higher
      acuity, not age, sex, time from previous visit, or change in chief complaint
      category, was associated directly with admission on the second visit.

PMID- 21878831
TI  - H1N1 hemagglutinin-inhibition seroprevalence in Emergency Department Health Care
      workers after the first wave of the 2009 influenza pandemic.
AB  - STUDY OBJECTIVE: The 2009 H1N1 pandemic (H1N1pdm) virus has been associated with
      high rates of asymptomatic infections. Existing influenza infection control
      policies do not address potential transmission through exposure to asymptomatic
      infected individuals in health care settings. We conducted a seroprevalence study
      of H1N1pdm infection to determine whether health care workers (HCWs) in the
      emergency department showed increased evidence of infection during the first wave
      of the pandemic than that previously reported in adults in the community.
      METHODS: Blood samples and demographic and clinical data were collected from
      eligible emergency department HCWs. Subjects' sera were tested for presence of
      antibodies specific for seasonal H1N1 and H1N1pdm viruses by hemagglutination
      inhibition assay. RESULTS: One hundred eight subjects were enrolled, of which 20
      (18.5%) were seropositive for H1N1pdm and 52 (48%) for seasonal H1N1. The median
      age of H1N1pdm-seropositive subjects was 32 years (range, 24-59 years). Of
      H1N1pdm-seropositive subjects, 35% were asymptomatic. Rates of H1N1pdm detection
      in HCWs (18.5%) were significantly higher than those observed previously in an
      identical age cohort in the community (2.6%, n = 262). CONCLUSIONS: The higher
      serodetection rates in adults observed in the current study suggest potentially
      significantly more frequent infections in HCWs than in the general population.
      Further investigations are needed to ascertain the relative incidence of
      influenza infections in HCWs and non-HCWs, to study influenza transmission by
      asymptomatic infected subjects and ascertain the burden of such transmission in
      health care settings.

PMID- 21878832
TI  - Primary repair of facial dog bite injuries in children.
AB  - OBJECTIVES: The management of dog bite wounds is controversial, and current data
      on risk of infection are variable and inconsistent. Furthermore, the use of
      prophylactic or empiric antibiotics for the treatment of these wounds is
      debatable. We investigate the rate of wound infections and other complications
      after primary repair of pediatric facial dog bite injuries. METHODS: We reviewed
      87 consecutive patients aged 18 years or younger who had facial dog bite injuries
      from January 2003 to December 2008. Variables examined were age, sex, setting of
      repair, number of sutures used for repair, whether surgical drains were used, and
      antibiotic administration. End points measured were incidence of wound infection,
      need for scar revision, and any wound complications. RESULTS: The mean age of
      patients was 6.8 years, and the majority were women (53%). All facial injuries
      were primarily repaired at the time of presentation either in the emergency
      department (ED; 46%), operating room (OR; 51%), or an outpatient setting (3%).
      All patients received an antibiotic course, none of the patients developed wound
      infection, and no subsequent scar revisions were performed. Three patients
      repaired in the OR underwent placement of a total of 4 closed-suction drains. The
      mean (SD) age of patients repaired in the OR was significantly younger than those
      repaired in the ED (5.7 [3.9] vs 8.0 [4.5] years, respectively; P < 0.01). The
      number of sutures used were greater for patients repaired in the OR than in the
      ED (66.4 [39.6] vs 21.7 [12.5], respectively; P < 0.01). CONCLUSIONS:
      Intuitively, younger patients and patients with greater severity injuries are
      more likely to undergo repair in the OR, and this was supported by our data.
      Overall, we found that primary repair of pediatric facial dog bite injuries,
      including complex soft-tissue injuries, is safe when performed in conjunction
      with antibiotic administration; however, further cross-specialty studies are
      needed to fully characterize these end points in a larger population.

PMID- 21878833
TI  - Adolescent female with urinary symptoms: a diagnostic challenge for the
      pediatrician.
AB  - OBJECTIVES: The objective of this study was to determine the accuracy with which
      physicians diagnose sexually transmitted infections (STIs) and urinary tract
      infections (UTIs) in adolescent females with urinary symptoms. Secondary aims
      were to determine the prevalence of STIs and UTIs in this subset of patients and
      to identify variables associated with a physician diagnosis of STI or UTI.
      METHODS: We performed a prospective cross-sectional study of females aged 13 to
      21 years who presented to an urban pediatric emergency department with urinary
      symptoms. Pediatric emergency medicine physicians' diagnoses of STI or UTI were
      compared with the criterion standard of diagnosis. RESULTS: Of the 233 patients
      enrolled, 211 had complete data sets and were included for analysis. Nineteen
      patients (9%) had STIs. Physicians predicted STIs in 35 patients (17%), of which
      9 (25%) had true infections. Sexually transmitted infections in 10 patients (53%)
      were underdiagnosed, in 26 patients (74%) were overdiagnosed, and in 9 patients
      (26%) were correctly diagnosed. One hundred twenty patients (57%) had UTIs.
      Physicians predicted UTIs in 156 patients (74%), of which 107 (69%) had culture
      confirmed UTIs. Urinary tract infections in 13 patients (11%) were
      underdiagnosed, in 49 patients (31%) were overdiagnosed, and in 107 patients
      (66%) were correctly diagnosed. Thirteen patients (6%) had a coinfection with
      both an STI and a UTI. CONCLUSIONS: Pediatric emergency medicine physicians both
      underdiagnose and overdiagnose STIs and UTIs in patients with urinary symptoms.
      This diagnostic challenge necessitates that all adolescent patients presenting
      with urinary symptoms should be tested for STIs and UTIs and have adequate follow
      up means established to ensure timely treatment.

PMID- 21878834
TI  - Mycophenolic acid-related diarrhea is not associated with polymorphisms in SLCO1B
      nor with ABCB1 in renal transplant recipients.
AB  - OBJECTIVE: We investigated the association between genetic polymorphisms in ABCB1
      and SLCO1B and mycophenolic acid (MPA) pharmacokinetics, and MPA-related diarrhea
      and leukopenia in 338 kidney transplant recipients. METHODS: A total of 338
      patients participating in an international, randomized-controlled clinical trial
      were genotyped for ABCB1 and SLCO1B. Patients were all treated with mycophenolate
      mofetil and either cyclosporine or tacrolimus. MPA-area under the curve (AUCs),
      MPA-glucuronide AUCs and acylglucuronide-AUCs were measured on days 3 and 10, and
      months 1, 3, 6, and 12 after kidney transplantation. RESULTS: The risk of
      developing diarrhea was 1.8-fold higher in patients cotreated with tacrolimus
      compared with patients cotreated with cyclosporine (95% confidence interval: 1.03
      3.13; P=0.038). ABCB1 and SLCO1B SNPs were not associated with dose-adjusted
      exposure to MPA, MPA-glucuronide, nor acylglucuronide-MPA nor with the incidence
      of diarrhea or leukopenia. CONCLUSION: Genotyping for ABCB1 or SLCO1B
      pretransplantation is unlikely to be of clinical value for individualization of
      MPA therapy.

PMID- 21878835
TI  - Human N-acetyltransferase 1 *10 and *11 alleles increase protein expression
      through distinct mechanisms and associate with sulfamethoxazole-induced
      hypersensitivity.
AB  - OBJECTIVES: N-acetyltransferase 1 (NAT1) metabolizes drugs and environmental
      carcinogens. NAT1 alleles *10 and *11 have been proposed to alter protein level
      or enzyme activity compared with wild-type NAT1 *4 and to confer cancer risk,
      through uncertain pathways. This study characterizes regulatory polymorphisms and
      underlying mechanisms of NAT1 expression. METHODS: We measured allelic NAT1 mRNA
      expression and translation, as a function of multiple transcription start sites,
      alternative splicing, and three 3'-polyadenylation sites in human livers (one of
      which was discovered in this study), B lymphocytes, and transfected cells. In a
      clinical study of 469 patients with HIV/AIDS treated with the NAT1/NAT2 substrate
      sulfamethoxazole (SMX), associations were tested between SMX-induced
      hypersensitivity and NAT1 *10 and *11 genotypes, together with known NAT2
      polymorphisms. RESULTS: NAT1 *10 and *11 were determined to act as common
      regulatory alleles accounting for most NAT1 expression variability, both leading
      to increased translation into active protein. NAT1 *11 (2.4% minor allele
      frequency) affected 3'-polyadenylation site usage, thereby increasing formation
      of NAT1 mRNA with intermediate length 3'-untranslated region (major isoform) at
      the expense of the short isoform, resulting in more efficient protein
      translation. NAT1 *10 (19% minor allele frequency) increased translation
      efficiency without affecting 3'-untranslated region polyadenylation site usage.
      Livers and B-lymphocytes with *11/*4 and *10/*10 genotypes displayed higher NAT1
      immunoreactivity and NAT1 enzyme activity than the reference genotype *4/*4.
      Patients who carry *10/*10 and *11/*4 (fast NAT1 acetylators) were less likely to
      develop hypersensitivity to SMX, but this was observed only in individuals who
      are also carrying a slow NAT2 acetylator genotype. CONCLUSION: NAT1 *10 and *11
      significantly increase NAT1 protein level/enzyme activity, enabling the
      classification of carriers into reference and rapid acetylators. Rapid NAT1
      acetylator status seems to protect against SMX toxicity by compensating for slow
      NAT2 acetylator status.

PMID- 21878836
TI  - Rasagiline interferes with neurodegeneration in the Prph2/rds mouse.
AB  - PURPOSE: Rasagiline (N-propargyl-1(R)-aminoindan) is a second-generation
      propargylamine with neuroprotective effects. We used the Prph2/rds mouse to
      assess the effect of rasagiline on photoreceptor cell death and to examine the
      possible modulation of different pathways of programmed cell death. METHODS: The
      animals were orally treated with various doses of rasagiline from Postnatal Day 1
      to 56. Methodological approaches consisted of morphometric analyses of the outer
      nuclear layer thickness and investigation of apoptotic events using TUNEL (TdT
      mediated dUTP-biotin nick end labeling) assay, immunohistochemistry, and
      immunoblot staining. The expression of programmed cell death marker genes
      involved in photoreceptor degeneration was studied by quantitative real-time
      polymerase chain reaction. RESULTS: In the Prph2/rds mouse, treatment resulted in
      a significant dose-dependent neuroprotection at Postnatal Day 56 and a delay in
      the induction of apoptotic events at Postnatal Day 14. Programmed cell death
      marker gene expression showed that several mechanisms were involved in
      photoreceptor degeneration. Furthermore, rasagiline did not only target apoptosis
      but also other pathways such as autophagy and inflammation. CONCLUSION: This
      study showed for the first time significant neuroprotective effects of rasagiline
      in the retina of Prph2/rds mice through caspase-dependent pathways. However, the
      activation of caspase-independent programmed cell death pathways that are not
      affected by rasagiline eventually led to retinal degeneration, but in a delayed
      manner.

PMID- 21878837
TI  - The association between drusen extent and foveolar choroidal blood flow in age
      related macular degeneration.
AB  - PURPOSE: To investigate the relationship between drusen extent and foveolar
      choroidal blood flow in nonexudative age-related macular degeneration. METHODS:
      Total drusen area, average druse area, and total drusen number were determined
      using a computer program developed to quantify the extent of manually outlined
      drusen from fundus photographs of 157 patients (239 eyes) with nonexudative age
      related macular degeneration. Laser Doppler flowmetry was used to assess relative
      choroidal blood velocity (ChBVel), volume (ChB Vol), and flow (ChBF low) in the
      center of the fovea. RESULTS: We found a significant inverse relationship between
      total drusen area and ChB Vol or ChB Flow. For every 1-mm2 increase in total
      drusen area, ChB Vol decreased by 0.0061 arbitrary units (P = 0.03) and ChBF low
      decreased by 0.23 arbitrary units (P = 0.049). Average druse area was also
      significantly inversely related to ChB Vol and ChBF low. For every 0.01-mm2
      increase in average druse area, the ChB Vol decreased by 0.0149 arbitrary units
      (P = 0.001) and the ChB Flow decreased by 0.4951 arbitrary units (P = 0.003).
      Adjustment for age weakened the significance, although it remained strong for
      average druse area versus ChB Flow (P = 0.017) and ChB Vol (P = 0.004). The
      computer-aided quantification of drusen used in this study showed high intra- and
      intergrader agreement. CONCLUSION: In patients with nonexudative age-related
      macular degeneration, there is an association between increased drusen extent and
      decreased ChB Vol and ChB Flow. This suggests the presence of ischemia and
      possibly the reason why patients with high-risk drusen are prone to advanced
      disease.

PMID- 21878838
TI  - Clinical utility of molecular surveillance for cytomegalovirus after antiviral
      prophylaxis in high-risk solid organ transplant recipients.
AB  - BACKGROUND: Cytomegalovirus (CMV) disease after discontinuation of prophylaxis is
      a significant problem for CMV-seronegative recipients of CMV-seropositive organs
      (donor seropositive and recipient seronegative [D+/R-]). Virologic monitoring
      after prophylaxis has been proposed as a way to prevent late-onset disease.
      METHODS: We reviewed the efficacy of this strategy. CMV D+/R- organ transplant
      recipients received 3 to 6 months of antiviral prophylaxis, and then viral loads
      were performed weekly for 8 weeks. Preemptive antiviral therapy was initiated at
      a predefined threshold. RESULTS: Seventy-one CMV D+/R- patients were assessed.
      Symptomatic CMV disease occurred in 29 of 71 (40.8%) patients during the first
      year posttransplant. A significant portion of disease occurred only after the 8
      week surveillance period (n=16). Viremia occurred in 19 of 71 (26.8%) patients
      during the 8-week surveillance. Preemptive therapy was successfully used in only
      3 of 19 (15.8%) viremic patients with no further disease development. The
      remaining patients cleared low-level viremia spontaneously (n=3) or had CMV
      disease (n=13) either at the first detection of viremia or before preemptive
      therapy initiation because of rapid viral load doubling (median doubling time 1.1
      days). CONCLUSION: CMV D+/R- patients had significant incidence of late-onset
      disease after prophylaxis. However, the use of a preemptive after prophylaxis
      strategy was of limited benefit in this group because of rapid viral doubling
      times and disease occurring after the surveillance period.

PMID- 21878839
TI  - African American living-kidney donors should be screened for APOL1 risk alleles.
AB  - The adjusted rate of end-stage kidney disease (ESKD) among African Americans is
      markedly increased relative to European Americans. African Americans are
      overrepresented on the kidney transplantation waiting list and experience longer
      wait times. In aggregate, these pressures drive recommendations for living donor
      transplantation. Genovese et al. recently implicated the APOL1 gene in ESKD risk
      among African Americans (Genovese et al. Science 2010; 329: 841). The presence of
      two APOL1 risk alleles doubles the relative risk for ESKD; moreover, the alleles
      are prevalent among African Americans. We propose a strategy for screening for
      the presence of APOL1 risk alleles among African American living kidney donors
      and for living-related donors for African American recipients.

PMID- 21878842
TI  - Pharmacokinetic analysis of topotecan after superselective ophthalmic artery
      infusion and periocular administration in a porcine model.
AB  - PURPOSE: To characterize the vitreous and plasma pharmacokinetics of topotecan
      after ophthalmic artery infusion (OAI) subsequent to superselective artery
      catheterization and to compare it with periocular injection (POI). METHODS: The
      ophthalmic artery of 4 pigs was catheterized and 1 mg of topotecan infused over a
      period of 30 minutes. The contralateral eye was subsequently used for
      administering topotecan by POI. Serial vitreous specimens were obtained by
      microdialysis and plasma samples collected and assayed for total and lactone
      topotecan. RESULTS: Maximum total topotecan concentration in the vitreous
      (median, range) was significantly higher after OAI compared with POI (131.8 ng/mL
      [112.9-138.7] vs. 13.6 ng/mL [5.5-15.3], respectively; P < 0.005). Median
      vitreous exposure calculated as area under the curve for total topotecan attained
      after OAI was significantly higher than after POI (299.8 ng.hour/mL [247.6-347.2]
      and 48.9 ng.hour/mL [11.8-63.4], respectively; P < 0.05). The vitreous to plasma
      exposure ratio was 29 after OAI and 3.4 after POI. Systemic exposure for total
      topotecan was low after both modalities of administration, with a trend to be
      lower after OAI compared with POI (10.6 ng.hour/mL [6.8-13.4] vs. 18.7 ng.hour/mL
      [6.3-21.7]; P = 0.54). CONCLUSION: Superselective OAI resulted in significantly
      higher vitreous concentrations and exposure and a trend toward lower systemic
      exposure than POI.

PMID- 21878840
TI  - Ganciclovir transiently attenuates murine cytomegalovirus-associated renal
      allograft inflammation.
AB  - BACKGROUND: Prophylactic ganciclovir (GCV) is used in high-risk renal transplant
      patients to prevent acute cytomegalovirus (CMV) disease, but its impact on
      inflammation within the allograft itself remains undefined. METHODS: To study the
      effect of GCV prophylaxis on allograft inflammation, murine CMV (MCMV)-infected
      allografts were analyzed in a murine donor positive/recipient negative allogeneic
      renal transplantation model by flow cytometry and immunofluorescent staining.
      RESULTS: By flow cytometry, CD45+ leukocyte infiltrates were more abundant in
      MCMV-infected allografts at 14 days posttransplant compared with uninfected
      grafts (P<0.01) and decreased in the presence of GCV (P<0.05). CD11c+ dendritic
      cells, Gr-1+ myeloid cells, CD204+ macrophages, and CD49b+ natural killer cells
      were reduced in GCV-treated allografts compared with MCMV-infected grafts without
      GCV treatment (P<0.05). However, GCV failed to reduce these cell types to levels
      found in MCMV-uninfected allografts. By day 7 after cessation of GCV prophylaxis,
      dendritic cells, macrophages, and natural killer cells increased in number and
      became statistically indistinguishable from numbers of cells found in MCMV
      infected allografts without GCV. GCV treatment did not affect the numbers of
      CD4+, CD8+, or CD19+/B220+ lymphocytes infiltrating the allografts. Infiltrates
      were confirmed histologically by immunofluorescent staining for CD3+ and CD11b+
      cells. CONCLUSIONS: In this model, MCMV-infected allografts developed
      significantly greater innate and adaptive leukocytic infiltrates compared with
      uninfected grafts. GCV attenuated the MCMV-associated innate leukocyte
      infiltrates in infected allografts but not the lymphocytic infiltrates. The
      attenuated innate response was limited to the period of GCV prophylaxis.

PMID- 21878843
TI  - Oral mifepristone for chronic central serous chorioretinopathy.
AB  - BACKGROUND: Chronic central serous chorioretinopathy (CCSC) can result in
      permanent loss of vision. Unfortunately, many cases of CCSC are not eligible or
      do not respond to treatment with thermal laser or photodynamic therapy.
      Glucocorticoids have been implicated in the pathogenesis of central serous
      chorioretinopathy. Mifepristone, an oral glucocorticoid receptor antagonist, may
      be helpful in cases of CCSC. METHODS: Mifepristone 200 mg was administered orally
      to 16 CCSC subjects in 2 separate protocols for up to 12 weeks. Visual acuity,
      examination, angiography, optical coherence tomography, and liver function were
      monitored during the treatment period. RESULTS: Favorable response to oral
      mifepristone was seen in CCSC patients with seven subjects gaining five or more
      letters of vision and seven subjects having improved optical coherence tomography
      findings. Treatment was well tolerated without serious adverse effects.
      CONCLUSION: Systemic glucocorticoid receptor antagonism with daily oral
      mifepristone does have a beneficial effect in treating some cases of CCSC.
      Further study is warranted.

PMID- 21878844
TI  - Determination of retinal and vitreous temperature in vitrectomy.
AB  - PURPOSE/BACKGROUND: To maximize recovery after neurologic injury, physicians use
      therapeutic hypothermia of 90 degrees F to 93 degrees F (32.2-33.9 degrees C).
      Temperatures below this are avoided because of increased side effects. The extent
      to which the retina is cooled during routine vitreous surgery is unknown. This
      study seeks to describe the temperature changes of the vitreous and retinal
      surface during vitreous surgery. METHODS: In this prospective study of 6 patients
      undergoing vitrectomy, a 23-gauge thermoprobe was used to measure intraocular
      temperatures before, during, and after vitrectomy. RESULTS: Before vitrectomy,
      the mean midvitreous temperature was 93.1 degrees F (33.9 degrees C) and retinal
      temperature was 94.7 degrees F to 95.4 degrees F (34.8-35.2 degrees C). During
      vitrectomy, the mean midvitreous cavity temperature was 76.9 degrees F (24.9
      degrees C) and retinal temperature was 83.2 degrees F to 85.1 degrees F (28.4
      29.5 degrees C). After completion of vitrectomy and with a closed infusion line,
      the mean midvitreous cavity temperature was 87.0 degrees F (30.6 degrees C) and
      retinal temperature was 90.1 degrees F to 90.9 degrees F (32.3-32.7 degrees C).
      These changes in temperature before, during, and after vitrectomy were found to
      be statistically significant. CONCLUSION: During routine vitreous surgery, the
      vitreous cavity and retina are cooled to much lower temperatures than those used
      in therapeutic hypothermia. Rapid rewarming occurs within the eye once the
      infusion line is closed.

PMID- 21878845
TI  - Predictive factors for visual outcome to intravitreal bevacizumab in young
      Chinese patients with myopic choroidal neovascularization.
AB  - PURPOSE: To report the anatomical and functional outcomes of intravitreal
      bevacizumab in both young and old Chinese patients with myopic choroidal
      neovascularization. METHODS: Consecutive series of 56 eyes (52 patients) with
      myopic choroidal neovascularization treated exclusively with intravitreal
      bevacizumab were reviewed retrospectively. Data from clinical examination, fundus
      photography, fluorescein angiography, and optical coherence tomography were
      collected. RESULTS: Vision significantly improved after intravitreal bevacizumab
      in this patient series (P < 0.0001), with an average of 2.2 injections. Higher
      myopia was positively correlated to a worse outcome (r = -0.3, P = 0.036).
      Stratifying by age, the correlation between spherical equivalent and final
      outcome showed statistical significance (r = -0.44, P = 0.027) only in younger
      patients. In younger patients, both spherical equivalent (P = 0.036) and initial
      visual acuity (P = 0.004) were predictive factors for visual outcome after
      adjusting for age, spherical equivalent, and number of injections, whereas in
      older patients, only initial visual acuity (P < 0.0001) was predictive of visual
      outcome after similar adjustments. CONCLUSION: Younger patients do not have a
      better outcome when compared with older patients. Initial visual acuity,
      regardless of age, plays a more significant role. Both initial visual acuity and
      spherical equivalent are predictive factors for final visual acuity in young
      Chinese patients.

PMID- 21878846
TI  - Increased retinal blood flow velocity in patients with early diabetes mellitus.
AB  - PURPOSE: To compare retinal blood flow velocity in small vessels of patients with
      early diabetes mellitus (DM), without any morphologic changes related to diabetic
      retinopathy, with that in a control group. METHODS: The authors used the retinal
      function imager to measure blood flow velocities, from many small vessels,
      simultaneously. Twenty-three eyes of 14 patients with early DM and 51 eyes of 31
      healthy subjects were enrolled. Differences between the patients and the control
      group were assessed by mixed linear models. RESULTS: Venous average velocity
      significantly increased in the DM group (3.8 +/- 1.2 vs. 2.9 +/- 0.5 mm/second, P
      < 0.0001) than in the healthy subjects. Arterial velocity of DM patients was also
      significantly higher (4.7 +/- 1.7 vs. 4.1 +/- 0.9 mm/second, P = 0.03). There was
      no statistically significant difference between groups in age, gender, heart
      rate, and systolic blood pressure. The diastolic blood pressure in the DM
      patients was lower than that in the healthy group (P = 0.03). CONCLUSION: There
      was an increase in arterial and venous retinal blood flow velocities of patients
      with early DM with no diabetic retinopathy. These findings support the notion
      that abnormalities in vessel function exist in diabetic eyes before the
      development of structural changes. This noninvasive approach facilitated the
      assessment of early hemodynamic abnormalities and may assist in screening and
      monitoring.

PMID- 21878847
TI  - Topical aqueous suppression does not significantly affect duration of intraocular
      gas tamponade after vitrectomy.
AB  - PURPOSE: To determine if topical aqueous suppression affects the duration of
      intraocular sulfur hexafluoride (SF6) gas tamponade after pars plana vitrectomy.
      METHODS: A prospective randomized controlled trial was conducted on patients
      undergoing 23-gauge sutured pars plana vitrectomy with air-fluid exchange and 20%
      SF6 gas tamponade. Eyes were randomly assigned to receive either postoperative
      topical dorzolamide 2%-timolol 0.5% twice a day or no additional drops (control
      group). Standard postoperative topical antibiotics and corticosteroids were used
      by all patients. RESULTS: A total of 21 patients were recruited for the study.
      Four were excluded because of noncompliance with use of dorzolamide-timolol. In
      the remaining 17 patients, 8 were randomly assigned to the dorzolamide-timolol
      group and 9 to the control group. Topical dorzolamide-timolol drops twice a day
      did not affect the duration of SF6 gas tamponade after pars plana vitrectomy
      (17.1 vs. 18.1 days with no drops, P = 0.35). The difference in mean gas duration
      was -1.0 days with a 95% confidence interval of -3.2 days to 1.2 days. Secondary
      analyses did not reveal a difference in SF6 duration based on lens status,
      presence of diabetes or hypertension, vitrectomy versus combined buckle with
      vitrectomy, or patient age. CONCLUSION: Topical aqueous suppression with
      dorzolamide-timolol does not have a large effect on duration of SF6 gas tamponade
      after pars plana vitrectomy.

PMID- 21878848
TI  - The value of two-field pattern electroretinogram in routine clinical
      electrophysiologic practice.
AB  - PURPOSE: To investigate the clinical use of the large-field pattern
      electroretinogram (PERG) as an adjunct test to the International-standard PERG in
      an unselected sequential cohort of patients referred for routine
      electrophysiologic assessment. METHODS: Pattern electroretinograms to both 15
      degrees  * 11 degrees  (International Society for Clinical Electrophysiology of
      Vision Standard) and 30 degrees  * 22 degrees  (large field) checkerboard field
      sizes were recorded in 277 consecutive electrophysiology patients, aged 10-79
      years. Most patients had additional tests including full-field electroretinogram,
      electrooculogram, multifocal electroretinograms, or cortical visual evoked
      potential. Patient data were compared with data from 27 control subjects.
      RESULTS: Satisfactory 2-field PERG data were obtained in 91% (N = 253) of
      patients; data from 24 patients (9%) were excluded because of poor compliance (n
      = 17) or nystagmus (n = 7). Standard PERGs were consistent with macular
      dysfunction in 44% of cases; large-field PERG revealed macular dysfunction in an
      additional 8% of eyes and helped to distinguish between localized central,
      predominantly paracentral, and widespread macular dysfunction. The results were
      consistent with multifocal electroretinogram and/or imaging studies on the same
      patients. In some patients with optic nerve disease, the large-field PERG
      provided clearer evidence of normal macular function than the standard PERG.
      CONCLUSION: Routine use of the large-field PERG is a valuable complement to
      standard-field PERG testing in the evaluation and management of patients with
      different forms of macular or generalized retinal dysfunction and can be useful
      in patients with optic nerve disease.

PMID- 21878849
TI  - Internal limiting membrane peeling as prophylaxis of macular pucker formation in
      eyes undergoing retinectomy for severe proliferative vitreoretinopathy.
AB  - BACKGROUND: The purpose of this was to analyze the effect of internal limiting
      membrane (ILM) peeling on the anatomical and functional outcomes in patients
      undergoing retinectomy for proliferative vitreoretinopathy-related retinal
      detachment, especially regarding the postoperative development of macular pucker.
      METHODS: In all, a consecutive and prospective series of 84 eyes of 84 patients
      were included in the study. All eyes underwent retinectomy with silicone oil
      tamponade for retinal detachment because of proliferative vitreoretinopathy. In
      Group A (33 eyes), the ILM was also peeled; in Group B (51 eyes), the ILM was
      left intact. Each patient gave consent to be included in the study, and no
      patient was lost to follow-up. Postoperatively, careful slit-lamp examination
      with a contact lens was used to determine whether primary ILM peeling was
      effective in preventing macular pucker formation. Various statistical methods
      were used to analyze the significance of the results with a P value of <= 0.05
      interpreted as significant. RESULTS: In Group A, the mean age of the patients was
      57.2 +/- 12.8 years and in Group B 54.6 +/- 14.5 years. Median follow-up in Group
      A was 28.2 +/- 7.2 months and in Group B 27.4 +/- 6.5 months. The mean time
      interval between the last retinectomy and silicone oil removal was 9.2 +/- 6.1
      months in Group A and 8.8 +/- 3.0 months in Group B. The mean follow-up after
      silicone oil removal was 17.4 +/- 10.3 months in Group A and 15.1 +/- 9.3 months
      in Group B. The mean logarithm of the minimum angle of resolution visual acuity
      at the final follow-up visit was 1.89 +/- 0.87 in Group A and 1.85 +/- 0.83 in
      Group B (P = 0.6, t-test). Extramacular epiretinal cellular proliferation
      occurred in 3 eyes (9%) in Group A in the first month after retinectomy and in 3
      eyes (5.8%) in Group B (P = 0.27, Fisher exact test). These epiretinal membranes,
      extending to the edge of the retinotomy, were stable during the follow-up period.
      No case of macular pucker was observed in Group A, but macular pucker was
      observed in 9 eyes (17.6%) in Group B at the final examination (P = 0.008, Fisher
      exact test). CONCLUSION: Primary peeling of the ILM allowed complete removal of
      all the epiretinal membranes and successfully prevented the development of
      macular pucker. Retinectomy and silicone oil tamponade proved an effective
      treatment modality for eyes with retinal detachment due to proliferative
      vitreoretinopathy.

PMID- 21878850
TI  - One-year choroidal thickness results after photodynamic therapy for central
      serous chorioretinopathy.
AB  - PURPOSE: To retrospectively evaluate choroidal thickness 1 year after
      photodynamic therapy in eyes with central serous chorioretinopathy using optical
      coherence tomography. METHODS: Central serous chorioretinopathy was diagnosed
      using fluorescein angiography, and indocyanine green angiography was used to
      evaluate choroidal vascular hyperpermeability. We measured the subfoveal
      choroidal thickness using enhanced depth imaging optical coherence tomography.
      RESULTS: Thirteen eyes (13 patients; average age, 56.8 years) with central serous
      chorioretinopathy were observed 1 year after half-dose photodynamic therapy with
      verteporfin. The mean subfoveal choroidal thickness decreased significantly from
      397 +/- 108 MUm at baseline to 323 +/- 120 MUm at 1 month, 312 +/- 117 MUm at 3
      months, 317 +/- 117 MUm at 6 months, and 321 +/- 122 MUm at 1 year (P < 0.01, for
      each comparison with baseline). However, the subfoveal choroid thickness
      significantly increased 2 days after photodynamic therapy to 441 +/- 120 (P <
      0.01) compared with baseline. Central serous chorioretinopathy did not recur in
      any patient. Indocyanine green angiography images at 3 months showed less
      choroidal vascular hyperpermeability compared with baseline. CONCLUSION: Half
      dose photodynamic therapy for central serous chorioretinopathy resulted in
      thinner subfoveal choroidal thickness 1 month after treatment, decreased the
      choroidal vascular hyperpermeability, and maintained the remission for 1 year.
      Enhanced depth imaging optical coherence tomography was helpful for monitoring
      the pathophysiologic choroidal changes in central serous chorioretinopathy.

PMID- 21878851
TI  - Association between high-risk disease loci and response to anti-vascular
      endothelial growth factor treatment for wet age-related macular degeneration.
AB  - PURPOSE: To investigate whether there is an association between known age-related
      macular degeneration genetic risk variants in the CFH, ARMS2, and HTRA1 genes and
      response to anti-vascular endothelial growth factor (VEGF) (ranibizumab or
      bevacizumab) treatment for wet age-related macular degeneration. METHODS: A
      retrospective review of 150 patients with documented wet age-related macular
      degeneration based on clinical examination and fluorescein angiogram was
      performed. Patients received anti-VEGF therapy with ranibizumab and/or
      bevacizumab. Patients were genotyped for the single-nucleotide polymorphism
      rs1061170, rs10490924, rs3750848, rs3793917, rs11200638, and rs932275 and for the
      indel del443ins54 spanning the CFH, ARMS2, and HTRA1 genes. RESULTS: There were
      57 patients who were characterized as negative responders to anti-VEGF therapy,
      and 93 patients who were characterized as positive responders. There was no
      significant difference in mean baseline visual acuity between the groups.
      Negative responders were followed for a mean duration of 24.0 months, while
      positive responders were followed for a mean duration of 22.0 months. Although
      the frequency of the at-risk alleles was higher in the positive responders when
      compared with the negative responder, this did not reach statistical
      significance. Additionally, there was no significant association between genotype
      and the number of injections or absolute change in visual acuity in both groups
      of responders. CONCLUSION: In our patient cohort, there was no statistically
      significant association between response to anti-VEGF therapy and the genotype in
      both positive-responder and negative-responder groups. Larger studies with more
      power are necessary to further determine whether a pharmacogenetic association
      exists between wet age-related macular degeneration and anti-VEGF therapy.

PMID- 21878852
TI  - Evaluation of retinal nerve fiber layer thickness in patients with retinitis
      pigmentosa using spectral-domain optical coherence tomography.
AB  - PURPOSE: To measure the peripapillary retinal nerve fiber layer (RNFL) thickness
      using spectral-domain optical coherence tomography in patients with retinitis
      pigmentosa. METHODS: Fifty eyes of 30 patients with retinitis pigmentosa
      underwent a complete ocular examination, including best-corrected visual acuity
      using a Snellen chart, slit-lamp biomicroscopic examination, and Goldmann
      applanation intraocular pressure measurement. Dilated fundus examination was
      performed using both direct and indirect ophthalmoscopy. In addition, all
      patients underwent peripapillary RNFL thickness measurements using an OPKO
      spectral-domain optical coherence tomography (OPKO Instrumentations, Miami, FL).
      RESULTS: The mean (+/- SD) age of the study cohort was 45.8 (+/- 16.3) years. Of
      the 50 eyes, 18 (36%) showed a thinning of the peripapillary RNFL in 1 or more
      quadrants and 21 (42%) showed a thickening of the peripapillary RNFL in 1 or more
      quadrants. Four eyes (8%) showed both thinning and thickening of the
      peripapillary RNFL thickness. The overall circumferential RNFL thickness of the
      14 eyes that showed only thinning in at least 1 quadrant was 78.78 MUm. For the
      17 eyes that showed only thickening in at least 1 quadrant, the RNFL thickness
      was 119.69 MUm. The values of the eyes with thinning and the eyes with thickening
      were significantly different from normal (t = 6.31 and P < 0.01 for thickening; t
      = 3.62 and P < 0.01 for thinning). CONCLUSION: Using spectral-domain optical
      coherence tomography testing, we demonstrated in the current study that the
      peripapillary RNFL thickness in patients with RP can be decreased, increased, or
      maintained within normal limits. Assessment of the RNFL thickness seems prudent
      in these patients, particularly for identifying notable degrees of RNFL thinning
      in those being considered for future therapeutic trials.

PMID- 21878853
TI  - Quantification of fluorescein-stained drusen associated with age-related macular
      degeneration.
AB  - BACKGROUND: Previous studies of age-related macular degeneration have not
      quantified the number of drusen that accumulate fluorescein. Histopathologic
      studies have demonstrated druse subregions with different degrees of
      hydrophobicity, and these subregions might potentially exhibit different degrees
      of fluorescein uptake. METHODS: We evaluated macular drusen from 35 age-related
      macular degeneration patients by measuring druse area in color digital images and
      fluorescein angiograms, using 2 morphometric methods. RESULTS: Of 828 drusen
      evaluated, 405 had a corresponding fluorescein angiogram signal. About half of
      all drusen per eye (49.57%) stained in each participant. Among fluorescein
      stained drusen, druse size measured in color images did not differ significantly
      from the sizes measured in corresponding fluorescein images (P = 0.8105), across
      the range of druse sizes. CONCLUSION: These findings indicate that our
      understanding of drusen subregion staining may not directly correlate to in vivo
      observations of macular drusen in age-related macular degeneration.

PMID- 21878854
TI  - Hemicentral retinal vein occlusion: natural history of visual outcome.
AB  - PURPOSE: To investigate the natural history of visual outcome in hemicentral
      retinal vein occlusion (HCRVO). METHODS: The study comprised 65 consecutive HCRVO
      patients (67 eyes) seen within 3 months of onset. At first visit, all patients
      had a detailed ophthalmic and medical history and comprehensive ophthalmic
      evaluation. Ophthalmic evaluation at initial and follow-up visits included
      recording visual acuity using the Snellen visual acuity chart, and visual fields
      with a Goldmann perimeter. Hemicentral retinal vein occlusion was classified into
      nonischemic (57 eyes) and ischemic (10 eyes) at initial visit. RESULTS:
      Nonischemic HCRVO involved superior and inferior half of the retina in 39% and
      56%, respectively, and in ischemic HCRVO in 50% and 40%, respectively. In
      nonischemic HCRVO, initial visual acuity was 20/60 or better in 73.7% and minimal
      to mild visual field loss in 96% and in ischemic HCRVO in 40% and 55.5%,
      respectively. After resolution of macular edema, in nonischemic HCRVO eyes,
      cumulative chance of improvement was 50% with 20/70 or worse initial visual
      acuity, and deterioration in only 6% with 20/60 or better initial visual acuity,
      and in 5% with minimal to mild visual initial field loss. CONCLUSION: This study
      suggests a good prognosis in the natural history of visual outcome in nonischemic
      HCRVO.

PMID- 21878855
TI  - Comparison of choroidal thickness among patients with healthy eyes, early age
      related maculopathy, neovascular age-related macular degeneration, central serous
      chorioretinopathy, and polypoidal choroidal vasculopathy.
AB  - PURPOSE: To compare choroidal thicknesses among eyes with early age-related
      maculopathy (ARM), neovascular age-related macular degeneration, polypoidal
      choroidal vasculopathy, and central serous chorioretinopathy. METHODS: Patients
      with age-related maculopathy (37 eyes), neovascular age-related macular
      degeneration (24 eyes), polypoidal choroidal vasculopathy (12 eyes), and central
      serous chorioretinopathy (31 eyes) underwent spectral-domain optical coherence
      tomography evaluations using a choroid scanning protocol. A horizontal linear
      section comprising 50 averaged scans was obtained of each macula. The choroidal
      thickness was measured from the outer border of the retinal pigment epithelium to
      the inner scleral border. Twenty-nine subjects with healthy eyes served as a
      control group. Analysis of covariance tests were performed to evaluate the
      effects of various diagnoses on choroidal thickness after removal of variance
      (covariates = gender, age, and refractive error). RESULTS: Among the different
      covariates, age was associated with choroidal thickness (fovea: F = 12.067, P =
      0.001). After controlling for age differences, the choroid was thicker in
      polypoidal choroidal vasculopathy (319.92 +/- 68.66 MUm) and central serous
      chorioretinopathy (367.81 +/- 105.56 MUm) patients than in controls (241.97 +/-
      66.37 MUm) and age-related maculopathy patients (186.62 +/- 64.02 MUm). However,
      there were no significant differences in mean choroidal thickness between
      neovascular age-related macular degeneration (226.46 +/- 102.87 MUm) and any of
      the other diagnoses. CONCLUSION: The choroid was thicker in eyes with polypoidal
      choroidal vasculopathy or central serous chorioretinopathy than in control or age
      related maculopathy groups.

PMID- 21878856
TI  - Clinical presentations and therapeutic effect of presumed choroidal tuberculosis.
AB  - PURPOSE: To present the clinical findings and to evaluate the therapeutic
      response to systemic antituberculosis (anti-TB) therapy in 18 cases of presumed
      choroidal TB. METHODS: Retrospective noncomparative interventional case series.
      Eighteen patients underwent a complete ophthalmologic examination and relevant
      laboratory and radiologic investigations. All patients were treated with systemic
      anti-TB therapy accordingly. RESULTS: In 18 cases of choroidal TB, there were 8
      men and 10 women ranging in age from 8 years to 52 years. Ten patients also had
      evidence of pulmonary TB and among of them, two patients had coexistent central
      nervous system TB, one patient had lymphoid TB, and one patient had abdominal TB.
      Those cases had varied clinical presentations including tubercle, tuberculoma,
      multifocal choroiditis, serpiginous like choroiditis, and/or diffuse choroiditis.
      Two cases (11.1%) had bilateral presentation. All patients were referred to a TB
      specialist to initiate a full standard course of anti-TB therapy according to the
      guideline of Centers for Disease Control and Prevention. Aside from one case,
      which worsened to panophthalmitis, the others responded to anti-TB therapy very
      well. None of the patients had human immunodeficiency virus and none was
      immunocompromised. CONCLUSION: Choroidal TB may present as variable clinical
      manifestations and occasionally be misdiagnosed as intraocular tumor or
      metastatic tumor. In our case series, the prognosis of this disease was well by
      giving systemic anti-TB therapy. So all ophthalmologists especially in developing
      countries should have a high degree of clinical suspicion to maximally maintain
      visual acuity.

PMID- 21878857
TI  - Early neural and vascular changes in the adolescent type 1 and type 2 diabetic
      retina.
AB  - PURPOSE: This cross-sectional study examines the existence and frequency of
      functional and structural abnormalities in the adolescent Type 1 diabetic retina.
      We also compare the results with those of adolescents with Type 2 diabetes.
      METHODS: Thirty-two adolescents with Type 1 diabetes (5.7 +/- 3.6 years; mean
      duration +/- SD), 15 with Type 2 diabetes (2.1 +/- 1.3 years), and 26 age-matched
      control subjects were examined. Multifocal electroretinogram responses from 103
      retinal regions were recorded. Optical coherence tomography was used to measure
      retinal thickness. Vascular diameter around the optic nerve was also assessed.
      RESULTS: Nine of the 32 (28%) adolescents with Type 1 diabetes and 6 of the 15
      (40%) with Type 2 diabetes had significant multifocal electroretinogram implicit
      time delays compared with 2 of the 26 controls (8%). Retinal thicknesses in both
      patient groups were significantly (P <= 0.01) thinner than controls. The Type 2
      group also showed significant (P <= 0.03) retinal venular dilation (235.8 +/- 5.9
      MUm) compared with controls (219.6 +/- 4.0 MUm). CONCLUSION: The present study
      illustrates that subtle but significant functional and structural changes occur
      very early in Type 1 diabetes. Adolescents with Type 2 diabetes appear to be more
      affected than those with Type 1 diabetes. Further longitudinal examination of the
      etiology and progression of these abnormalities is warranted.

PMID- 21878858
TI  - A practical approach to new (5Z) 2-alkylthio-5-arylmethylene-1-methyl-1,5-dihydro
      4H-imidazol-4-one derivatives.
AB  - A practical protocol for the preparation of (5Z)-2-alkylthio-5-arylmethylene-1
      methyl-1,5-dihydro-4H-imidazol-4-one derivatives is reported. The new compounds
      were obtained in good yield and stereoselectivity in two steps, namely a solvent
      free Knoevenagel condensation under microwave irradiation, followed by an S
      alkylation reaction with various halogenoalkanes.

PMID- 21878859
TI  - Microwave-assisted extraction of oxymatrine from Sophora flavescens.
AB  - In this paper, microwave-assisted extraction (MAE) of oxymatrine from Sophora
      flavescens were studied by HPLC-photodiode array detection. Effects of several
      experimental parameters, such as concentration of extraction solvent, ratio of
      liquid to material, microwave power, extraction temperature, and extraction time
      on the extraction efficiencies of oxymatrine were evaluated. The optimal
      extraction conditions were 60% ethanol, a 20:1 (v/v) ratio of liquid to material
      and extraction for 10 min at 50  degrees C under 500 W microwave irradiation.
      Under the optimum conditions, the yield of oxymatrine was 14.37 mg/g. The crude
      extract obtained could be used as either a component of some complex traditional
      medicines or for further isolation and purification of bioactive compounds. The
      results, which indicated that MAE is a very useful tool for the extraction of
      important phytochemicals from plant materials, should prove helpful for the full
      utilization of Sophora flavescens.

PMID- 21878860
TI  - Antioxidant capacity of Ocimum basilicum L. and Origanum vulgare L. extracts.
AB  - The antioxidant properties of five different extracts (Et2O, CHCl3, EtOAc, n
      BuOH, and H2O) of Ocimum basilicum L. and Origanum vulgare L. were studied.
      Antioxidant activity was assessed in six different model systems. Free radical
      scavenging capacity (RSC) was evaluated by measuring the scavenging capacity of
      extracts on DPPH, NO, O2*- and OH radical, as well as on hydrogen peroxide
      (H2O2). In addition, the protective effects on lipid peroxidation in liposomes
      (LPx) were evaluated by TBA-assay using the Fe2+/ascorbate induction system. The
      amount of total phenolic compounds and content of total flavonoids was also
      determined. EtOAc, n-BuOH and H2O extracts of O. basilicum and O. vulgare
      expressed very strong scavenger activity. Furthermore, the mentioned extracts
      showed notable inhibition of LPx. On the other hand, Et2O and CHCl3 extracts
      showed much weaker effect in the neutralization of DPPH, NO and O2*- radicals and
      the neutralization of H2O2. When examining the production of OH radicals and
      inhibition of LPx, the Et2O and CHCl3 extracts showed weak prooxidative
      properties. The observed differences in antioxidant activity could be partially
      explained by the levels of phenolics and flavonoids in the investigated O.
      basilicum and O. vulgare extracts.

PMID- 21878861
TI  - Long-acting insulin analogue detemir compared with NPH insulin in type 1
      diabetes: a systematic review and meta-analysis.
AB  - INTRODUCTION: Although numerous studies showed an improvement in glycemic control
      in type 1 diabetic patients treated with long-acting insulin analogue detemir
      compared with Neutral Protamine Hagedorn (NPH) insulin, the beneficial effects of
      insulin detemir has not been confirmed by all investigators. OBJECTIVES: The aim
      of the study was to compare the effect of treatment with detemir insulin vs. NPH
      insulin on metabolic control, hypoglycemic episodes, and body weight gain in
      patients with type 1 diabetes by means of a systematic review and a meta
      analysis. METHODS: The following electronic databases were searched up to
      November 2010: MEDLINE, EMBASE, and the Cochrane Library. Additional references
      were obtained from the reviewed articles. Only randomized controlled trials of at
      least 12-week duration with basal-bolus regimen therapies using detemir insulin
      vs. NPH insulin were included. RESULTS: The analysis included 10 studies
      involving 3825 patients with type 1 diabetes. Combined data from all trials
      showed a statistically significant reduction in hemoglobin A1c (HbA1c) (weighted
      mean difference: [WMD] -0.073, 95% CI -0.135 to -0.011, P = 0.021) in the detemir
      group compared with the NPH group. There was also a significant reduction of
      fasting plasma glucose (FPG) (WMD - 0.977 mmol/l, 95% CI -1.395 to -0.558, P
      <0.001), all-day hypoglycemic episodes (relative risk [RR] 0.978, 95% CI 0.961
      0.996), severe hypoglycemic episodes (RR 0.665, 95% CI 0.547-0.810), nocturnal
      hypoglycemic episodes (RR 0.877, 95% CI 0.816-0.942), as well as smaller body
      weight gain (WMD -0.779 kg, 95% CI -0.992 to -0.567) in patients using detemir
      insulin compared with those using NPH insulin. CONCLUSIONS: Basal-bolus treatment
      with insulin detemir, as compared with NPH insulin, provided a minor benefit in
      terms of the HbA1c value and significantly reduced FPG in type 1 diabetic
      patients. Treatment with detemir insulin was also superior to NPH insulin in
      reducing the risk of all-day, nocturnal, and severe hypoglycemic episodes, with
      the added benefit of reduced weight gain.

PMID- 21878862
TI  - Should we have any doubts about hypertension therapy in elderly patients?:
      ACCF/AHA 2011 expert consensus document on hypertension in the elderly.
AB  - Hypertension therapy in elderly patients still constitutes a considerable
      challenge. Its importance is also emphasized by the fact that, nowadays, many
      international organizations focus on the problem of an aging society (in 2030,
      life expectancy at birth in the European Union 27 is expected to rise to 85.3
      years for women and 80.0 years for men). They discuss not only the optimal
      therapy in elderly patients, the problem of compliance and polypragmasy, but also
      the quality of life as well as the social, economic, and psychological challenges
      associated with this patient group. However, neither the available trials nor the
      European Society of Hypertension guidelines (2009) finally answered all important
      questions on hypertension management in elderly people. Thus, the first official
      recommendations on hypertension therapy in this patient group were much expected.
      The American College of Cardiology Foundation/American Heart Association 2011
      Expert Consensus Document on Hypertension in the Elderly was published on April
      25, 2011. The present article summarizes the most important issues discussed in
      this document.

PMID- 21878863
TI  - Explanatory and pragmatic clinical trials: a primer and application to a recent
      asthma trial.
AB  - Most clinical trials assessing the role of a specific intervention attempt to
      answer an explanatory question: under ideal circumstances of risk and
      responsiveness, can the expert care of individual with a particular condition
      reduce their risks of a relevant but restricted set of outcomes? Such explanatory
      trials (also called efficacy trials) are of direct relevance to expert clinicians
      and their highly compliant patients. Another question, potentially of broader
      clinical or health care policy relevance is: Does this treatment improve patient
      important outcomes when applied by typical clinicians to typical patients?
      Answering this latter question is the goal of pragmatic trial, also labeled by
      some as "management" or "effectiveness" trial. The methodological and
      organizational differences between explanatory and pragmatic trials include,
      among others, patients eligibility (restricted to highly responsive and compliant
      patients in explanatory trials vs. everyone with condition of interest in
      pragmatic trials), experimental and comparator intervention (blinded and
      inflexible with strict instructions vs. flexible with cross-over permitted and no
      blinding), types of practitioners (only those with documented high expertise vs.
      all who usually provide given mode of care), and outcome measurement (often
      limited to biologic effects vs. broad overall health effects sometimes based on
      administrative data bases on mortality and utilization). Those aspects of study
      design and conduct and their role in determining a place of an intervention in
      clinical practice are reviewed in this paper.

PMID- 21878864
TI  - Effect of inhaled corticosteroids on small airway inflammation in patients with
      bronchial asthma.
AB  - Bronchial asthma is a chronic inflammatory disease affecting the bronchial
      mucosa. In asthma patients, the highest number of inflammatory cells, including
      eosinophils, are found in the small bronchi. According to the most recent 2006
      report of the Global Initiative for Asthma, inhaled corticosteroids (ICS) remain
      the first-line treatment of chronic asthma. They are characterized by high lung
      deposition and good distribution in the small bronchi, which makes them
      particularly efficient in reducing chronic inflammatory infiltrate in the small
      airways. Good pulmonary distribution of ICS in patients with mild asthma is
      reflected by a better control of the disease, improvement in the quality of life,
      improvement in the results of pulmonary function tests, decreased levels of
      exhaled proinflammatory nitric oxide, lower number of inflammatory cells
      (including eosinophils) in the induced sputum, decrease in bronchial
      hyperreactivity, and decrease in exhaled air trapping observed in the computed
      tomographic scanning of the lungs.

PMID- 21878865
TI  - Intraoperative neurophysiological monitoring by anesthesiologists.

PMID- 21878866
TI  - Monitored anesthesia care and ophthalmic surgery. Challenge or "easy-going"?

PMID- 21878867
TI  - Electrophysiologic neuromonitoring during repair of the thoracoabdominal aorta by
      anesthesiologists.
AB  - BACKGROUND: Surgical repair of the thoracoabdominal aorta is associated with risk
      of spinal ischemia. Electrophysiologic neuromonitoring reduces this risk, but is
      usually performed by neurophysiologists not always available. In this study
      repair of the thoracoabdominal aorta monitored by anesthesiologists has been
      investigated. METHODS: Somatosensory and transcranial electrical motor evoked
      potentials were monitored in 20 patients. A lumbar intraspinal fluid drainage was
      inserted. Dacron graft replacement of the aorta was performed by sequentially
      clamping during partial cardiopulmonary bypass. Loss or decrease of amplitudes of
      evoked potentials of more than 50% prompted reinsertion of spinal arteries in the
      graft. RESULTS: One patient not monitored with motor evoked potentials due to
      indwelling cardiac pacemaker had postoperative paraplegia. Somatosensory and
      motor evoked potentials were recordable in all other patients. Two patients died
      during surgery, one patient died postoperatively. No surviving patient monitored
      with somatosensory and motor evoked potentials had neurologic deficits.
      CONCLUSION: Electrophysiologic neuromonitoring during surgical repair of the
      descending aorta can be successfully provided by anesthesiologists and should be
      predominately encouraged where neurophysiologists are not available due to
      organizational or financial shortcomings.

PMID- 21878868
TI  - Changes in calculated arterio-jugular venous glutamate difference and SjvO2 in
      patients with severe traumatic brain injury.
AB  - BACKGROUND: Cerebral metabolic impairment is feared to induce secondary brain
      damage following traumatic brain injury (TBI). The present study was designed to
      assess the temporal profile of calculated arterio- jugular venous differences in
      glutamate (AJVDglu) and SjvO(2) in patients subjected to continuous pharmacologic
      coma. Metabolic impairment was assumed to be reflected by increased jugular
      venous glutamate levels and decreased jugular venous oxygen saturation (SjvO(2)).
      METHODS: Arterial and jugular venous blood was drawn once daily for up to 14 days
      from 14 patients to assess the temporal profile. Plasma glutamate was measured by
      high performance liquid chromatography. SjvO(2), lactate and paCO(2) were
      determined in routine blood gas analysis. Calculated AJVD indirectly reflects
      cerebral uptake (positive values) or cerebral release (negative values). RESULTS:
      During pharmacologic coma an increase in ICP approaching 20 mmHg was associated
      with significantly reduced paCO(2) (4.7 +/- 0.5 kPa; mean +/- standard
      deviation), markedly decreased SjvO(2) (66.0 +/- 4.2%) without reaching ischemic
      values, and a trend to more negative AJVDglu values (-6.0 +/- 14.3 MUmol/L),
      suggesting cerebral glutamate release. Arterio- jugular venous lactate difference
      (AJVDlac) remained unchanged. CONCLUSION: During pharmacologic coma increased ICP
      was associated with significantly decreased SjvO(2) which coincided only with a
      trend to increased cerebral glutamate release. Calculated AJVDglu appears to be
      inferior in unmasking altered brain metabolism compared to SjvO(2) whenever ICP
      is increased.

PMID- 21878869
TI  - Systemic adverse events during 2005 phacoemulsifications under monitored
      anesthesia care: a prospective evaluation.
AB  - BACKGROUND: The aim of the study was to evaluate the systemic adverse events
      triggering on-call anesthesiologist's intervention during 2005
      phacoemulsification under topical anesthesia on a day-surgery monitored
      anesthesia care regimen. METHODS: Adverse events triggering an anesthesiologist
      call by the attending nurse were registered. Comorbidities (7 categories), age,
      gender, body mass index, ASA status, length of surgery, time of the day of
      surgery and operated eye (first/second) were analyzed as potentially predictive
      factors. Odds Ratios are expressed as OR (95% CI). RESULTS: The anesthesiologist
      was called in 433 (21.6%) cases: age (5-yr-OR 0.95 [0.91-0.99]), ASA status 3-4
      (OR 1.37 [1.02-1.85]), positive neurological history (OR 1.60 [1.06-2.40]),
      positive psychiatric history (OR 2.56 [1.34-4.93]) and length of surgery (OR 1.03
      [1.01-1.06]) were predictive of the anesthesiologist call. Arterial hypertension
      (10.3%) and agitation (9.5%) were the most frequent adverse events. Age (5-yr-OR
      1.27 [1.16-1.38]) and ASA status 3-4 (OR 1.83 [1.30-2.56]) were predictive of
      arterial hypertension. Age (5-yr-OR 0.80 [0.76-0.85]), positive neurological
      history (OR 1.86 [1.10-3.14]) and positive psychiatric history (OR 4.48 [2.26
      8.88]) were predictive of agitation. Interruption of surgery was never required.
      CONCLUSION: One-day cataract surgery performed under topical anesthesia with
      monitored anesthesia care required anesthesiologist intervention in 21.6% of
      cases, mainly because of agitation or hypertension. Agitation occurred more often
      in younger patients with neurological or psychiatric comorbidities. Hypertension
      occurred more often in older patients with higher ASA scores.

PMID- 21878870
TI  - Management of acute respiratory complications from influenza A (H1N1) infection:
      experience of a tertiary-level Intensive Care Unit.
AB  - BACKGROUND: The novel influenza A (H1N1) pandemic was associated with an epidemic
      of critical illness. METHODS: We describe the clinical profiles of critically ill
      patients with severe complications due to microbiologically confirmed pandemic
      influenza A (H1N1) infection admitted to a medical ICU in Monza, Italy, over a 6
      month period. RESULTS: From August 2009 to January 2010, 19 patients (13 adults
      and 6 children) required ICU admission. Nine subjects were referred to our
      hospital from other ICUs. In all patients, with the exception of a case of severe
      septic shock, the cause of ICU admission was acute respiratory failure. Other
      nonpulmonary organ failures were common. A trial of non-invasive ventilation was
      attempted in 13 cases and was successful in four of them. The majority of the
      patients required invasive mechanical ventilation. In the 7 most severely
      hypoxemic patients, we applied veno-venous ECLS, with a very high rate of
      success. The median ICU stay was 9 days (range 1-78 days). Sixteen out of 19
      (84%) patients survived. CONCLUSION: In the majority of our patients, critical
      illness caused by pandemic influenza A (H1N1) was associated with severe
      hypoxemia, multiple organ failure, requirement for mechanical ventilation and
      frequent use of rescue therapies and ECLS support.

PMID- 21878871
TI  - Invasive and non-invasive long-term mechanical ventilation in Italian children.
AB  - BACKGROUND: To date, few studies have been published regarding the number of
      children in Italy who require long-term mechanical ventilation (LTV) and their
      underlying diagnoses, ventilatory needs and hospital discharge rate. METHODS: A
      preliminary national postal survey was conducted and identified 535 children from
      57 centers. Detailed data were then obtained for 378 children from 30 centers.
      RESULTS: The estimated prevalence in Italy of this population was 4.3/100000. The
      majority of children (72.2%) were followed in pediatric units. The primary
      physicians who cared for these patients were either pediatric intensivists or
      pediatric pulmonologists. Neurological patients (78.2% of cases) represented the
      principal disorder category. 57.2% of the patients were non-invasively
      ventilated, with a nasal mask being the most common interface (85% of cases). The
      presence of clinical symptoms that were associated with abnormal findings on
      diagnostic testing was the primary indication for ventilatory support, whereas
      weaning failure was the primary indication for tracheotomy. Invasive ventilation
      was significantly related to younger age, longer daily hours on ventilation and
      cerebral palsy. Ventilatory modes with guaranteed minimal tidal volume were more
      often used in patients with tracheotomy. Despite their age, illness severity and
      need for technological care, 98% of the study population were successfully home
      discharged. CONCLUSION: Managing pediatric home LTV requires tremendous effort on
      the part of the patient's family and places a significant strain on community
      financial resources. In particular, neurological patients require more health
      care than patients in other categories. To further improve the quality of care
      for these patients, it is essential to establish a dedicated national database.

PMID- 21878872
TI  - Steroids in severe pneumonia: a literature review.
AB  - Despite more than sixty years of scientific medical research, severe pneumonia,
      either community-acquired or nosocomial, remains a leading cause of death
      regardless of the patients' immunity state. The clinical introduction of new and
      more potent antibiotic molecules and the continuous development of efficient
      respiratory assistance devices may not be able to radically improve the clinical
      outcome of pneumonia. Adjunctive therapies based on the physiopathological
      mechanisms of lung damage in severe pneumonia have been strongly advocated, and
      corticosteroids, which present many properties that theoretically interfere with
      these pathways, have been widely used, with conflicting results. The aim of this
      review is to examine existing literature data on steroid use in severe pneumonia.
      Molecular, endocrinological and clinical studies will be described to help
      physicians to clarify the reasons for the historical debate about steroid use as
      an adjunctive treatment in severe pneumonia. There is growing evidence that,
      during lung infection, an excessive inflammatory response can have deleterious
      effects and contribute to tissue damage mechanisms. Because of their
      immunomodulatory properties, glucocorticoids have been suggested as a useful tool
      for regulating the complex balance of cytokine networks, and they are commonly
      used as an adjunctive therapy during serious infections. In severe pneumonia,
      preclinical data, including cytokine level detection and animal studies, have
      shown encouraging results, although the clinical data is controversial. Moreover,
      large randomized controlled trials have not been conducted to determine steroid
      side effects and the risk of immunosuppression-induced superinfections. The
      benefits of steroid use in patients with severe pneumonia have not been proven by
      current literature, but ongoing investigations of anti-inflammatory molecules
      probably represent the key point of severe infection management in the near
      future.

PMID- 21878873
TI  - End of life care in Italian intensive care units: where are we now?
AB  - Most patients in the ICU are unable to make decisions for themselves at the end
      of life (EOL), and the responsibility for these decisions falls to the medical
      staff and patients' relatives. Therefore, clinicians must frequently communicate
      with patients' relatives to understand the patients' values and preferences as
      they perform medical decision making. The family's role in this process varies:
      the entire burden of decision making could rest with the family, or family
      members could be informed of the decisions without admission into the decision
      making process. In contrast to these two extremes, clinicians and family members
      may also enter into shared decision making: an exchange of views and opinions
      between clinicians and the patient's family to enable the two parties to reach
      decisions together. In this latter scenario, the effectiveness of the discussions
      that take place between clinicians and family members becomes a crucial marker of
      high-quality intensive care. In this review, we provide an overview of the
      current literature concerning the state of EOL care in European and Italian ICUs
      and then summarize several European and American recommendations for improving
      EOL care in the ICU. Finally, we examine the opportunity to use shared decision
      making to improve EOL care in the ICU through interdisciplinary communication,
      open and realistic discussion of prognosis with families, and an approach
      respecting different cultural perspectives.

PMID- 21878874
TI  - Are guidelines for non-invasive ventilation during weaning still valid?
AB  - Noninvasive ventilation (NIV) has gained increasing acceptance over the years to
      reduce endotracheal intubation, pneumonia and to prevent or treat respiratory
      failure in patients with different diagnoses. The international consensus
      conference, and the British society guidelines on NIV ventilation have analyzed
      its use during the weaning phase concluding that there were still conflicting
      results of its use. However, recent clinical trials have shown clear clinical
      benefits on the use of NIV in several patient populations during the weaning
      period. Acute respiratory failure (ARF) during the weaning process is the main
      object of recently published studies. The latest published randomized trials on
      the application of NIV for acute respiratory failure following extubation failed
      to demonstrate any favorable outcome. Even so, the use of NIV during the process
      of weaning in patients experiencing multiple weaning failure or as a preventive
      therapy in patients at higher risk of respiratory deterioration showed improved
      clinical outcomes only in chronic obstructive pulmonary disease and in particular
      in hypercapnic patients. Reduced invasive mechanical ventilation, tracheostomy
      and lower mortality rate at 90 days were the major advantages.

PMID- 21878875
TI  - When, where and how to initiate hypothermia after adult cardiac arrest.
AB  - Therapeutich hypothermia (TH) has been shown to improve neurological outcome and
      survival after witnessed cardiac arrest (CA) that is due to ventricular
      fibrillation. Although TH is widely used following witnessed CA as well as all
      forms of initial rhythm, the mortality rate after CA remains unacceptably high,
      and additional study is needed to understand when and how to implement
      hypothermia in the post-resuscitation phase. Experimental studies have emphasized
      the importance of initiating cooling soon after the return of spontaneous
      circulation (ROSC) or even during cardiopulmonary resuscitation (CPR). Clinical
      studies have shown that pre-hospital induction of hypothermia is feasible and has
      no major adverse events-even when used intra-arrest-and may provide some
      additional benefits compared to delayed in-hospital cooling. Thus, hypothermia
      use should not be limited to the Intensive Care Unit but can be initiated in the
      field/ambulance or in the Emergency Department, then continued after hospital
      admission- even during specific procedures such as coronary angiography-as part
      of the global management of CA patients. Various methods (both non-invasive and
      invasive) are available to achieve and maintain the target temperature; however,
      only some of these methods-which include cold fluids, ice packs, iced pads and
      helmet and trans-nasal cooling- are easily deployed in the pre-hospital setting.

PMID- 21878876
TI  - Combination of propofol and remifentanil target-controlled infusion for laryngeal
      mask airway insertion in children: some remarks.

PMID- 21878878
TI  - Delayed hemopneumothorax resulting from a ventriculoperitoneal shunt procedure.

PMID- 21878879
TI  - Stones: Passing a stone in your sleep might be easier than you think.

PMID- 21878881
TI  - Risk factors: Cigarette smoking increases the risk of coronary heart disease in
      women more than in men.

PMID- 21878880
TI  - Stable angina pectoris: antianginal therapies and future directions.
AB  - Advances in pharmacotherapy for stable angina have produced a wide choice of
      drugs with various mechanisms of action, potentially enabling individualized,
      patient-specific treatment strategies to be developed. In this Review, the
      various treatment options for patients with stable angina are discussed. Data
      from randomized, clinical trials of established and novel drugs are reviewed,
      with particular emphasis on the proposed mechanisms of action, benefits of
      therapy, and adverse-effect profiles. The role of coronary revascularization in
      conjunction with optimal medical therapy as a treatment strategy is discussed,
      although drug therapy might reduce the need for prompt revascularization if the
      procedure is being considered solely for the purpose of alleviating angina.
      Finally, trials to investigate stimulation of angiogenesis using growth-factor,
      gene, and cell therapy are used to illustrate the challenges of chemically
      inducing the growth of adequate, durable blood vessels.

PMID- 21878882
TI  - Anticoagulation therapy: Direct factor Xa inhibition improves stroke prevention
      in patients with AF.

PMID- 21878883
TI  - Transplantation: Does switching to a CNI-free regimen reduce cancer risk?

PMID- 21878884
TI  - Transplantation: mTOR inhibition in kidney transplant recipients.

PMID- 21878887
TI  - Transplantation: Good long-term outcomes after pediatric en bloc transplantation.

PMID- 21878885
TI  - Epidemiology and management of end-stage renal disease in the elderly.
AB  - Elderly patients with end-stage renal disease (ESRD) are at increased risk of
      developing aging-related problems, such as frailty, impaired physical function,
      falls, poor nutrition and cognitive impairment. These factors affect dialysis
      outcomes, which can be very poor in frail, elderly patients who often experience
      a decline in overall health and physical function and have short survival. The
      default treatment option for these patients is hospital-based hemodialysis, often
      with little consideration of how this modality will affect the survival or
      quality of life of individual patients. A comparison of quality of life of
      elderly patients on hemodialysis versus peritoneal dialysis shows that those on
      peritoneal dialysis have less illness intrusion. Assisted peritoneal dialysis
      enables a greater number of frail, elderly patients to have dialysis in their own
      homes. Dialysis may not extend survival for those with multiple comorbidities, so
      conservative care (nondialysis treatment) should be considered. To improve the
      outcomes of elderly patients with ESRD, it is necessary to develop a realistic
      approach to overall prognosis, quality of life and how the patient copes with the
      disabilities associated with aging. This approach includes having discussions
      regarding choice of treatment and end-of-life goals with patients and families.

PMID- 21878888
TI  - Measuring fatigue in rheumatoid arthritis.

PMID- 21878889
TI  - Rituximab in AAV: when and how to use it.

PMID- 21878890
TI  - Expanding horizons in metastatic prostate cancer treatment.

PMID- 21878892
TI  - Hematology: New hope for lymphoma patients.

PMID- 21878891
TI  - Challenges translating breast cancer gene signatures into the clinic.
AB  - The advent of microarray-based gene-expression profiling a decade ago raised high
      expectations for rapid advances in breast cancer classification, prognostication
      and prediction. Despite the development of molecular classifications, and
      prognostic and predictive gene-expression signatures, microarray-based studies
      have not yielded definitive answers to many of the questions that remain germane
      for the successful implementation of personalized medicine. There are a lack of
      robust signatures to predict benefit from specific therapeutic agents and it is
      still not possible to predict prognosis or chemotherapy treatment response in
      specific disease subsets accurately, such as triple-negative breast cancer. We
      discuss the hurdles in the development and validation of molecular classification
      systems, and prognostic and predictive signatures based on microarray gene
      expression profiling. We suggest that similar challenges are likely to be
      encountered in translating next-generation sequencing data into clinically useful
      information. Finally we highlight strategies for the development of clinically
      useful molecular predictors in the future.

PMID- 21878894
TI  - Targeted therapies: Front-line therapy in lung cancer with mutations in EGFR.

PMID- 21878895
TI  - Thyroid cancer: finding the malignant thyroid nodule in the haystack.

PMID- 21878898
TI  - Diabetes: type 1 diabetes mellitus--a door opening to a real therapy?

PMID- 21878899
TI  - Nutrition: dietary fat might influence serum vitamin D level.

PMID- 21878900
TI  - Derivation of insulin producing cells from human endometrial stromal stem cells
      and use in the treatment of murine diabetes.
AB  - Pancreatic islet cell transplantation is an effective approach to treat type 1
      diabetes, however the shortage of cadaveric donors and limitations due to
      rejection require alternative solutions. Multipotent cells derived from the
      uterine endometrium have the ability to differentiate into mesodermal and
      ectodermal cellular lineages, suggesting the existence of mesenchymal stem cells
      in this tissue. We differentiated human endometrial stromal stem cells (ESSC)
      into insulin secreting cells using a simple and nontransfection protocol. An in
      vitro protocol was developed and evaluated by assessing the expression of pan
      beta-cell markers, followed by confirmation of insulin secretion. PAX4, PDX1,
      GLUT2, and insulin, were all increased in differentiated cells compared to
      controls. Differentiated cells secreted insulin in a glucose responsive manner.
      In a murine model, differentiated cells were injected into the kidney capsules of
      diabetic mice and human insulin identified in serum. Within 5 weeks blood glucose
      levels were stabilized in animals transplanted with differentiated cells, however
      those treated with undifferentiated cells developed progressive hyperglycemia.
      Mice transplanted with control cells lost weight and developed cataracts while
      those receiving insulin producing cells did not. Endometrium provides an easily
      accessible, renewable, and immunologically identical source of stem cells with
      potential therapeutic applications in diabetes.

PMID- 21878896
TI  - Molecular genetics and diagnosis of thyroid cancer.
AB  - Thyroid cancer is a common type of endocrine malignancy, and its incidence has
      been steadily increasing in many regions of the world. Initiation and progression
      of thyroid cancer involves multiple genetic and epigenetic alterations, of which
      mutations leading to the activation of the MAPK and PI3K-AKT signaling pathways
      are crucial. Common mutations found in thyroid cancer are point mutation of the
      BRAF and RAS genes as well as RET/PTC and PAX8/PPARgamma chromosomal
      rearrangements. The mutational mechanisms seem to be linked to specific etiologic
      factors. Chromosomal rearrangements have a strong association with exposure to
      ionizing radiation and possibly with DNA fragility, whereas point mutations
      probably arise as a result of chemical mutagenesis. A potential role of dietary
      iodine excess in the generation of BRAF point mutations has also been proposed.
      Somatic mutations and other molecular alterations have been recognized as helpful
      diagnostic and prognostic markers for thyroid cancer and are beginning to be
      introduced into clinical practice, to offer a valuable tool for the management of
      patients with thyroid nodules.

PMID- 21878901
TI  - New generation of plasmid backbones devoid of antibiotic resistance marker for
      gene therapy trials.
AB  - Since it has been established that the injection of plasmid DNA can lead to an
      efficient expression of a specific protein in vivo, nonviral gene therapy
      approaches have been considerably improved, allowing clinical trials. However,
      the use of antibiotic resistance genes as selection markers for plasmid
      production raises safety concerns which are often pointed out by the regulatory
      authorities. Indeed, a horizontal gene transfer to patient's bacteria cannot be
      excluded, and residual antibiotic in the final product could provoke allergic
      reactions in sensitive individuals. A new generation of plasmid backbones devoid
      of antibiotic resistance marker has emerged to increase the safety profile of
      nonviral gene therapy trials. This article reviews the existing strategies for
      plasmid maintenance and, in particular, those that do not require the use of
      antibiotic resistance genes. They are based either on the complementation of
      auxotrophic strain, toxin-antitoxin systems, operator-repressor titration, RNA
      markers, or on the overexpression of a growth essential gene. Minicircles that
      allow removing of the antibiotic resistance gene from the initial vector will
      also be discussed. Furthermore, reported use of antibiotic-free plasmids in
      preclinical or clinical studies will be listed to provide a comprehensive view of
      these innovative technologies.

PMID- 21878902
TI  - Combining mTor inhibitors with rapamycin-resistant T cells: a two-pronged
      approach to tumor elimination.
AB  - Despite activity as single agent cancer therapies, Rapamycin (rapa) and its
      rapalogs may have their greatest effects when combined with other therapeutic
      modalities. In addition to direct antitumor activity, rapalogs reverse multiple
      tumor-intrinsic immune evasion mechanisms. These should facilitate tumor-specific
      T cell activity, but since rapa directly inhibits effector T cells, this
      potential immune enhancement is lost. We hypothesized that if T cells were
      rendered resistant to rapa they could capitalize on its downregulation of tumor
      immune evasion. We therefore modified T cells with a rapa-resistant mutant of
      mTor, mTorRR, and directed them to B lymphomas by coexpressing a chimeric antigen
      receptor (CAR) for CD19 (CAR.CD19-28zeta). T cells expressing transgenic mTorRR
      from a piggyBac transposon maintain mTor signaling, proliferate in the presence
      of rapa and retain their cytotoxic function and ability to secrete interferon
      gamma (IFNgamma) after stimulation, effector functions that were inhibited by
      rapa in control T cells. In combination, rapa and rapa-resistant-CAR.CD19-28zeta
      expressing T cells produced greater antitumor activity against Burkitt's lymphoma
      and pre-B ALL cell lines in vitro than CAR.CD19-28zeta T cells or rapa alone. In
      conclusion, the combination of rapa and rapa-resistant, CAR.CD19-28zeta
      expressing T cells may provide a novel therapy for the treatment of B cell
      malignancies and other cancers.

PMID- 21878903
TI  - Retroviral gene therapy for X-linked chronic granulomatous disease: results from
      phase I/II trial.
AB  - X-linked chronic granulomatous disease (CGD) is an inherited immunodeficiency
      caused by a defect in the gp91(phox) gene. In an effort to treat X-CGD, we
      investigated the safety and efficacy of gene therapy using a retroviral vector,
      MT-gp91. Two X-CGD patients received autologous CD34(+) cells transduced with MT
      gp91 after a conditioning regimen consisting of fludarabine and busulfan. The
      level of gene-marked cells was highest at day 21 (8.3 and 11.7% in peripheral
      blood cells) but decreased to 0.08 and 0.5%, respectively, 3 years after gene
      transfer. The level of functionally corrected cells, as determined by
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase assay, reached a peak
      at day 17 (6.5% patient 1 (P1) and 14.3% patient 2 (P2) of total granulocytes)
      and declined to 0.05% (P1) and 0.21% (P2), 3 years later. Some retroviral vectors
      were found to have integrated within or close to the proto-oncogenes MDS1-EVI1,
      PRDM16, and CCND2; however, no abnormal cell expansion or related hematological
      malignancy was observed. Overall, the gene transfer procedure did not produce any
      serious adverse effects and was able to convert a significant fraction of blood
      cells to biologically functional cells, albeit for a short period of time.

PMID- 21878904
TI  - A double-modulation strategy in cancer treatment with a chemotherapeutic agent
      and siRNA.
AB  - 5-Fluorouracil (5-FU) is broadly considered the drug of choice for treating human
      colorectal cancer (CRC). However, 5-FU resistance, mainly caused by the
      overexpression of antiapoptotic proteins such as Bcl-2, often leads ultimately to
      treatment failure. We here investigated the effect of Bcl-2 gene silencing, using
      small interfering RNA (siRNA) (siBcl-2), on the efficacy of 5-FU in CRC.
      Transfection of siBcl-2 by a Lipofectamine2000/siRNA lipoplex effectively
      downregulated Bcl-2 expression in the DLD-1 cell line (a CRC), resulting in
      significant cell growth inhibition in vitro upon treatment with 5-FU. For in vivo
      treatments, S-1, an oral formulation of Tegafur (TF), a prodrug of 5-FU, was used
      to mimic 5-FU infusion. The combined treatment of polyethylene glycol (PEG)
      coated siBcl-2-lipoplex and S-1 showed superior tumor growth suppression in a DLD
      1 xenograft model, compared to each single treatment. Surprisingly, daily S-1
      treatment enhanced the accumulation of PEG-coated siBcl-2-lipoplex in tumor
      tissue. We propose a novel double modulation strategy in cancer treatment, in
      which chemotherapy enhances intratumoral siRNA delivery and the delivered siRNA
      enhances the chemosensitivity of tumors. Combination of siRNA-containing
      nanocarriers with chemotherapy may compensate for the limited delivery of siRNA
      to tumor tissue. In addition, such modulation strategy may be considered a
      promising therapeutic approach to successfully managing 5-FU-resistant tumors.

PMID- 21878905
TI  - ATP7A gene addition to the choroid plexus results in long-term rescue of the
      lethal copper transport defect in a Menkes disease mouse model.
AB  - Menkes disease is a lethal infantile neurodegenerative disorder of copper
      metabolism caused by mutations in a P-type ATPase, ATP7A. Currently available
      treatment (daily subcutaneous copper injections) is not entirely effective in the
      majority of affected individuals. The mottled-brindled (mo-br) mouse
      recapitulates the Menkes phenotype, including abnormal copper transport to the
      brain owing to mutation in the murine homolog, Atp7a, and dies by 14 days of age.
      We documented that mo-br mice on C57BL/6 background were not rescued by
      peripheral copper administration, and used this model to evaluate brain-directed
      therapies. Neonatal mo-br mice received lateral ventricle injections of either
      adeno-associated virus serotype 5 (AAV5) harboring a reduced-size human ATP7A
      (rsATP7A) complementary DNA (cDNA), copper chloride, or both. AAV5-rsATP7A showed
      selective transduction of choroid plexus epithelia and AAV5-rsATP7A plus copper
      combination treatment rescued mo-br mice; 86% survived to weaning (21 days),
      median survival increased to 43 days, 37% lived beyond 100 days, and 22% survived
      to the study end point (300 days). This synergistic treatment effect correlated
      with increased brain copper levels, enhanced activity of dopamine-beta
      hydroxylase, a copper-dependent enzyme, and correction of brain pathology. Our
      findings provide the first definitive evidence that gene therapy may have
      clinical utility in the treatment of Menkes disease.

PMID- 21878906
TI  - Blimp1 regulates the transition of neonatal to adult intestinal epithelium.
AB  - In many mammalian species, the intestinal epithelium undergoes major changes that
      allow a dietary transition from mother's milk to the adult diet at the end of the
      suckling period. These complex developmental changes are the result of a genetic
      programme intrinsic to the gut tube, but its regulators have not been identified.
      Here we show that transcriptional repressor B lymphocyte-induced maturation
      protein 1 (Blimp1) is highly expressed in the developing and postnatal intestinal
      epithelium until the suckling to weaning transition. Intestine-specific deletion
      of Blimp1 results in growth retardation and excessive neonatal mortality. Mutant
      mice lack all of the typical epithelial features of the suckling period and are
      born with features of an adult-like intestine. We conclude that the suckling to
      weaning transition is regulated by a single transcriptional repressor that delays
      epithelial maturation.

PMID- 21878907
TI  - Backbone rigidity and static presentation of guanidinium groups increases
      cellular uptake of arginine-rich cell-penetrating peptides.
AB  - In addition to endocytosis-mediated cellular uptake, hydrophilic cell-penetrating
      peptides are able to traverse biological membranes in a non-endocytic mode termed
      transduction, resulting in immediate bioavailability. Here we analysed structural
      requirements for the non-endocytic uptake mode of arginine-rich cell-penetrating
      peptides, by a combination of live-cell microscopy, molecular dynamics
      simulations and analytical ultracentrifugation. We demonstrate that the
      transduction efficiency of arginine-rich peptides increases with higher peptide
      structural rigidity. Consequently, cyclic arginine-rich cell-penetrating peptides
      showed enhanced cellular uptake kinetics relative to their linear and more
      flexible counterpart. We propose that guanidinium groups are forced into
      maximally distant positions by cyclization. This orientation increases membrane
      contacts leading to enhanced cell penetration.

PMID- 21878908
TI  - A segmental genomic duplication generates a functional intron.
AB  - An intron is an extended genomic feature whose function requires multiple
      constrained positions-donor and acceptor splice sites, a branch point, a
      polypyrimidine tract and suitable splicing enhancers-that may be distributed over
      hundreds or thousands of nucleotides. New introns are therefore unlikely to
      emerge by incremental accumulation of functional sub-elements. Here we
      demonstrate that a functional intron can be created de novo in a single step by a
      segmental genomic duplication. This experiment recapitulates in vivo the birth of
      an intron that arose in the ancestral jawed vertebrate lineage nearly half-a
      billion years ago.

PMID- 21878909
TI  - Arrays of Lucius microprisms for directional allocation of light and
      autostereoscopic three-dimensional displays.
AB  - Directional and asymmetric properties are attractive features in nature that have
      proven useful for directional wetting, directional flow of liquids and artificial
      dry adhesion. Here we demonstrate that an optically asymmetric structure can be
      exploited to guide light with directionality. The Lucius prism array presented
      here has two distinct properties: the directional transmission of light and the
      disproportionation of light intensity. These allow the illumination of objects
      only in desired directions. Set up as an array, the Lucius prism can function as
      an autostereoscopic three-dimensional display.

PMID- 21878910
TI  - Field measurements suggest the mechanism of laser-assisted water condensation.
AB  - Because of the potential impact on agriculture and other key human activities,
      efforts have been dedicated to the local control of precipitation. The most
      common approach consists of dispersing small particles of dry ice, silver iodide,
      or other salts in the atmosphere. Here we show, using field experiments conducted
      under various atmospheric conditions, that laser filaments can induce water
      condensation and fast droplet growth up to several MUm in diameter in the
      atmosphere as soon as the relative humidity exceeds 70%. We propose that this
      effect relies mainly on photochemical formation of p.p.m.-range concentrations of
      hygroscopic HNO(3), allowing efficient binary HNO(3)-H(2)O condensation in the
      laser filaments. Thermodynamic, as well as kinetic, numerical modelling based on
      this scenario semiquantitatively reproduces the experimental results, suggesting
      that particle stabilization by HNO(3) has a substantial role in the laser-induced
      condensation.

PMID- 21878911
TI  - Molecular mechanism for 3:1 subunit stoichiometry of rod cyclic nucleotide-gated
      ion channels.
AB  - Molecular determinants of ion channel tetramerization are well characterized, but
      those involved in heteromeric channel assembly are less clearly understood. The
      heteromeric composition of native channels is often precisely controlled. Cyclic
      nucleotide-gated (CNG) channels from rod photoreceptors exhibit a 3:1
      stoichiometry of CNGA1 and CNGB1 subunits that tunes the channels for their
      specialized role in phototransduction. Here we show, using electrophysiology,
      fluorescence, biochemistry, and X-ray crystallography, that the mechanism for
      this controlled assembly is the formation of a parallel 3-helix coiled-coil
      domain of the carboxy-terminal leucine zipper region of CNGA1 subunits,
      constraining the channel to contain three CNGA1 subunits, followed by
      preferential incorporation of a single CNGB1 subunit. Deletion of the carboxy
      terminal leucine zipper domain relaxed the constraint and permitted multiple
      CNGB1 subunits in the channel. The X-ray crystal structures of the parallel 3
      helix coiled-coil domains of CNGA1 and CNGA3 subunits were similar, suggesting
      that a similar mechanism controls the stoichiometry of cone CNG channels.

PMID- 21878912
TI  - Strong plasmonic enhancement of photovoltage in graphene.
AB  - From the wide spectrum of potential applications of graphene, ranging from
      transistors and chemical sensors to nanoelectromechanical devices and composites,
      the field of photonics and optoelectronics is believed to be one of the most
      promising. Indeed, graphene's suitability for high-speed photodetection was
      demonstrated in an optical communication link operating at 10 Gbit s(-1).
      However, the low responsivity of graphene-based photodetectors compared with
      traditional III-V-based ones is a potential drawback. Here we show that, by
      combining graphene with plasmonic nanostructures, the efficiency of graphene
      based photodetectors can be increased by up to 20 times, because of efficient
      field concentration in the area of a p-n junction. Additionally, wavelength and
      polarization selectivity can be achieved by employing nanostructures of different
      geometries.

PMID- 21878913
TI  - Human metabolic profiles are stably controlled by genetic and environmental
      variation.
AB  - 1H Nuclear Magnetic Resonance spectroscopy (1H NMR) is increasingly used to
      measure metabolite concentrations in sets of biological samples for top-down
      systems biology and molecular epidemiology. For such purposes, knowledge of the
      sources of human variation in metabolite concentrations is valuable, but
      currently sparse. We conducted and analysed a study to create such a resource. In
      our unique design, identical and non-identical twin pairs donated plasma and
      urine samples longitudinally. We acquired 1H NMR spectra on the samples, and
      statistically decomposed variation in metabolite concentration into familial
      (genetic and common-environmental), individual-environmental, and longitudinally
      unstable components. We estimate that stable variation, comprising familial and
      individual-environmental factors, accounts on average for 60% (plasma) and 47%
      (urine) of biological variation in 1H NMR-detectable metabolite concentrations.
      Clinically predictive metabolic variation is likely nested within this stable
      component, so our results have implications for the effective design of biomarker
      discovery studies. We provide a power-calculation method which reveals that
      sample sizes of a few thousand should offer sufficient statistical precision to
      detect 1H NMR-based biomarkers quantifying predisposition to disease.

PMID- 21878914
TI  - Cellular reprogramming by the conjoint action of ERalpha, FOXA1, and GATA3 to a
      ligand-inducible growth state.
AB  - Despite the role of the estrogen receptor alpha (ERalpha) pathway as a key growth
      driver for breast cells, the phenotypic consequence of exogenous introduction of
      ERalpha into ERalpha-negative cells paradoxically has been growth inhibition. We
      mapped the binding profiles of ERalpha and its interacting transcription factors
      (TFs), FOXA1 and GATA3 in MCF-7 breast carcinoma cells, and observed that these
      three TFs form a functional enhanceosome that regulates the genes driving core
      ERalpha function and cooperatively modulate the transcriptional networks
      previously ascribed to ERalpha alone. We demonstrate that these enhanceosome
      occupied sites are associated with optimal enhancer characteristics with highest
      p300 co-activator recruitment, RNA Pol II occupancy, and chromatin opening. Most
      importantly, we show that the transfection of all three TFs was necessary to
      reprogramme the ERalpha-negative MDA-MB-231 and BT-549 cells to restore the
      estrogen-responsive growth resembling estrogen-treated ERalpha-positive MCF-7
      cells. Cumulatively, these results suggest that all the enhanceosome components
      comprising ERalpha, FOXA1, and GATA3 are necessary for the full repertoire of
      cancer-associated effects of the ERalpha.

PMID- 21878915
TI  - The essential genome of a bacterium.
AB  - Caulobacter crescentus is a model organism for the integrated circuitry that runs
      a bacterial cell cycle. Full discovery of its essential genome, including non
      coding, regulatory and coding elements, is a prerequisite for understanding the
      complete regulatory network of a bacterial cell. Using hyper-saturated transposon
      mutagenesis coupled with high-throughput sequencing, we determined the essential
      Caulobacter genome at 8 bp resolution, including 1012 essential genome features:
      480 ORFs, 402 regulatory sequences and 130 non-coding elements, including 90
      intergenic segments of unknown function. The essential transcriptional circuitry
      for growth on rich media includes 10 transcription factors, 2 RNA polymerase
      sigma factors and 1 anti-sigma factor. We identified all essential promoter
      elements for the cell cycle-regulated genes. The essential elements are
      preferentially positioned near the origin and terminus of the chromosome. The
      high-resolution strategy used here is applicable to high-throughput, full genome
      essentiality studies and large-scale genetic perturbation experiments in a broad
      class of bacterial species.

PMID- 21878916
TI  - Making sense of chromatin states.
AB  - Researchers find new pieces in the puzzle of genome regulation.

PMID- 21878917
TI  - On target? Tracing zinc-finger-nuclease specificity.
AB  - In two independent studies, researchers experimentally test the cleavage
      specificity of zinc-finger nucleases across the genome.

PMID- 21878918
TI  - Beyond the rainbow: new fluorescent proteins brighten the infrared scene.
AB  - Two fluorescent proteins that emit in the far-red and infrared range for imaging
      applications in cells and in vivo are described.

PMID- 21878919
TI  - 'MiMICing' genomic flexibility.
AB  - A new collection of Minos transposon insertions will enhance the range and
      flexibility of genome engineering in Drosophila melanogaster.

PMID- 21878920
TI  - Three-dimensional biomaterials for the study of human pluripotent stem cells.
AB  - The self-renewal and differentiation of human pluripotent stem cells (hPSCs) have
      typically been studied in flat, two-dimensional (2D) environments. In this
      Perspective, we argue that 3D model systems may be needed in addition, as they
      mimic the natural 3D tissue organization more closely. We survey methods that
      have used 3D biomaterials for expansion of undifferentiated hPSCs, directed
      differentiation of hPSCs and transplantation of differentiated hPSCs in vivo.

PMID- 21878921
TI  - On the value of information and other rewards.

PMID- 21878922
TI  - Grilled RIBEYE stakes a claim for synaptic ribbons.

PMID- 21878923
TI  - Microglia and monocytes: 'tis plain the twain meet in the brain.

PMID- 21878924
TI  - 'Macrophage' cannabinoid receptor goes up in smoke.

PMID- 21878925
TI  - Coming up: in search of the vertical dimension in the brain.

PMID- 21878926
TI  - Erroneous analyses of interactions in neuroscience: a problem of significance.
AB  - In theory, a comparison of two experimental effects requires a statistical test
      on their difference. In practice, this comparison is often based on an incorrect
      procedure involving two separate tests in which researchers conclude that effects
      differ when one effect is significant (P < 0.05) but the other is not (P > 0.05).
      We reviewed 513 behavioral, systems and cognitive neuroscience articles in five
      top-ranking journals (Science, Nature, Nature Neuroscience, Neuron and The
      Journal of Neuroscience) and found that 78 used the correct procedure and 79 used
      the incorrect procedure. An additional analysis suggests that incorrect analyses
      of interactions are even more common in cellular and molecular neuroscience. We
      discuss scenarios in which the erroneous procedure is particularly beguiling.

PMID- 21878933
TI  - Scale: a chemical approach for fluorescence imaging and reconstruction of
      transparent mouse brain.
AB  - Optical methods for viewing neuronal populations and projections in the intact
      mammalian brain are needed, but light scattering prevents imaging deep into brain
      structures. We imaged fixed brain tissue using Scale, an aqueous reagent that
      renders biological samples optically transparent but completely preserves
      fluorescent signals in the clarified structures. In Scale-treated mouse brain,
      neurons labeled with genetically encoded fluorescent proteins were visualized at
      an unprecedented depth in millimeter-scale networks and at subcellular
      resolution. The improved depth and scale of imaging permitted comprehensive three
      dimensional reconstructions of cortical, callosal and hippocampal projections
      whose extent was limited only by the working distance of the objective lenses. In
      the intact neurogenic niche of the dentate gyrus, Scale allowed the quantitation
      of distances of neural stem cells to blood vessels. Our findings suggest that the
      Scale method will be useful for light microscopy-based connectomics of cellular
      networks in brain and other tissues.

PMID- 21878934
TI  - Accurate staging of axillary lymph nodes from breast cancer patients using a
      novel molecular method.
AB  - BACKGROUND: The one-step nucleic acid amplification (OSNA) assay is a molecular
      based lymph-node metastasis detection procedure that can assess a whole node and
      yields semi-quantitative results for the detection of clinically relevant nodal
      metastases. We aimed to determine the performance of the OSNA assay as an
      accurate nodal staging tool in comparison with routine histological examination.
      METHODS: Subjects comprised 183 consecutive patients with pT1-2 breast cancer who
      underwent axillary dissection after positive sentinel-node (SN) biopsy with the
      OSNA assay. Of these, for non-SN evaluation, 119 patients underwent OSNA assay
      evaluation, whereas 64 had single-section histology. We compared the detection
      rates of non-SN metastasis and upstaging rates from the SN stage according to the
      American Joint Committee on Cancer staging between the OSNA and histology
      cohorts. RESULTS: OSNA detected more cases of non-SN metastases than histology
      (OSNA 66/119, 55.5% vs histology 13/64, 20.3%; P<0.001), particularly
      micrometastases (36/119, 30.3% vs 1/64, 1.6%; P<0.001). Total upstaging rates
      were similar in both cohorts (20/119, 16.8% vs 9/64, 14.1%, P=0.79). CONCLUSION:
      OSNA detects a far greater proportion of non-SN micrometastases than routine
      histological examination. However, upstaging rates after axillary dissection were
      not significantly different between both cohorts. Follow-up of the OSNA cohort is
      required to determine its clinical relevance.

PMID- 21878935
TI  - Benefit finding and post-traumatic growth in long-term colorectal cancer
      survivors: prevalence, determinants, and associations with quality of life.
AB  - BACKGROUND: As research on quality of life of colorectal cancer (CRC) survivors
      has mainly focused on downsides of cancer survivorship, the aim of this study is
      to investigate benefit finding (BF) and post-traumatic growth (PTG) in long-term
      CRC survivors. METHODS: Benefit finding, PTG, and quality of life were assessed 5
      years after diagnosis in a population-based cohort of 483 CRC patients using the
      benefit finding scale, the post-traumatic growth inventory, and the EORTC QLQ
      C30. Prevalence of BF and PTG, determinants of moderate-to-high BF and PTG, and
      the association between BF, PTG, and quality of life were investigated. RESULTS:
      Moderate to high levels of BF and PTG were experienced by 64% and 46% of the
      survivors, respectively. Survivors with the highest level of education and with
      higher depression scores reported less BF and PTG. The PTG increased with
      increasing stage and self-reported burden of diagnosis. Quality of life only
      correlated weakly with PTG (Pearson's r=0.1180, P=0.0112) and not with BF
      (r=0.0537, P=0.2456). CONCLUSION: Many long-term CRC survivors experience BF and
      PTG. As these constructs were not strongly correlated with quality of life,
      focusing solely on quality of life after cancer misses an important aspect of
      survivorship.

PMID- 21878937
TI  - Predictors of survival in patients with recurrent ovarian cancer undergoing
      secondary cytoreductive surgery based on the pooled analysis of an international
      collaborative cohort.
AB  - BACKGROUND: This study aims to identify prognostic factors and to develop a risk
      model predicting survival in patients undergoing secondary cytoreductive surgery
      (SCR) for recurrent epithelial ovarian cancer. METHODS: Individual data of 1100
      patients with recurrent ovarian cancer of a progression-free interval at least 6
      months who underwent SCR were pooled analysed. A simplified scoring system for
      each independent prognostic factor was developed according to its coefficient.
      Internal validation was performed to assess the discrimination of the model.
      RESULTS: Complete SCR was strongly associated with the improvement of survival,
      with a median survival of 57.7 months, when compared with 27.0 months in those
      with residual disease of 0.1-1 cm and 15.6 months in those with residual disease
      of >1 cm, respectively (P<0.0001). Progression-free interval (<=23.1 months vs
      >23.1 months, hazard ratio (HR): 1.72; score: 2), ascites at recurrence (present
      vs absent, HR: 1.27; score: 1), extent of recurrence (multiple vs localised
      disease, HR: 1.38; score: 1) as well as residual disease after SCR (R1 vs R0, HR:
      1.90, score: 2; R2 vs R0, HR: 3.0, score: 4) entered into the risk model.
      CONCLUSION: This prognostic model may provide evidence to predict survival
      benefit from secondary cytoreduction in patients with recurrent ovarian cancer.

PMID- 21878936
TI  - High bone marrow angiopoietin-1 expression is an independent poor prognostic
      factor for survival in patients with myelodysplastic syndromes.
AB  - BACKGROUND: Angiogenic factors have an essential role in normal and pathologic
      angiogenesis. However, the clinical implication of angiogenic factor expression
      in myelodysplastic syndromes (MDS) remains unclear. METHODS: In this study, we
      sought to investigate the prognostic impact of the expression of genes encoding
      angiopoietin-1 (Ang-1), Ang-2, the receptor Tie2, vascular endothelial growth
      factor-A (VEGF-A) and VEGF-C in the bone marrow (BM) in 208 patients with newly
      diagnosed primary MDS. RESULTS: BM Ang-1 expression was significantly higher in
      MDS patients, especially those with higher-risk subtypes, than in normal
      controls. With a median follow-up time of 32.9 months, the disease transformed to
      acute leukaemia more frequently in the patients bearing higher Ang-1 expression
      than in those with lower expression (31.5% vs 18.6%, P=0.023). The MDS patients
      with higher Ang-1 expression had shorter overall survival than those with lower
      expression (median 20.8+/-4.5 months vs 63.3+/-17.8 months, P<0.001).
      Multivariate analyses showed that higher Ang-1 expression was an independent
      unfavourable prognostic factor for overall survival. There was no impact of the
      expression of other angiogenic factors on survival. CONCLUSION: BM Ang-1
      expression may serve as a new biomarker to predict clinical outcome in MDS
      patients.

PMID- 21878938
TI  - High levels of circulating CD34+ cells at autologous stem cell collection are
      associated with favourable prognosis in multiple myeloma.
AB  - BACKGROUND: High-dose chemotherapy with autologous stem cell transplantation is a
      cornerstone in the first-line treatment of multiple myeloma patients. However,
      only few factors have been identified affecting the outcome in such patients. We
      hypothesised that varying levels of mobilised CD34+ cells confer prognostic
      information in myeloma patients undergoing high-dose chemotherapy. METHODS: We
      determined circulating CD34+ cells at the day of peripheral stem cell collection
      in 158 consecutive myeloma patients between January 2001 and August 2010.
      Patients were stratified into two groups (super vs normal mobilisers) with a
      cutoff of 100,000 peripheral CD34+ cells per ml. RESULTS: We found that patients
      with more than 100,000 peripheral CD34+ cells per ml had a better overall
      survival (P=0.005) and a prolonged time to progression (P=0.0398) than patients
      with CD34+ cell counts below 100,000 CD34+ cells per ml. High levels of CD34+
      cells were an independent marker for better overall survival and time to
      progression in a multivariate analysis that included disease stage, response at
      transplant, light-chain subtype, age, sex, and height. CONCLUSION: Our results
      suggest that high levels of mobilised peripheral CD34+ cells are associated with
      favourable outcome in myeloma patients undergoing autologous transplantation.

PMID- 21878939
TI  - Intravenous bisphosphonate therapy and atrial fibrillation/flutter risk in cancer
      patients: a nationwide cohort study.
AB  - BACKGROUND: There is conflicting evidence regarding bisphosphonates and atrial
      fibrillation (AF) risk in osteoporosis patients. However, bisphosphonates are
      used in much higher doses in treatment of bone metastasis and hypercalcemia, but
      little is known about the AF risk in cancer patients. METHODS: We conducted a
      nationwide population-based cohort study using Danish databases. All cancer
      patients exposed to intravenous bisphosphonates during 2000-2008 were matched
      with two non-exposed cancer patients by cancer type, distant metastasis presence
      at diagnosis, age, and gender. We used Cox proportional hazard regression to
      estimate hazards ratios (HRs) of AF/flutter adjusting for important confounding
      factors. RESULTS: Of the 3981 cancer patients exposed to intravenous
      bisphosponates, 128 (3.2%) developed AF/flutter. This condition occurred in 192
      (2.4%) of the 7906 non-exposed cancer patients, corresponding to an adjusted HR
      of 1.7 (95% CI: 1.2-2.4). CONCLUSION: Intravenous bisphosphonates may increase
      AF/flutter risk in cancer patients.

PMID- 21878940
TI  - Erlotinib 'dosing-to-rash': a phase II intrapatient dose escalation and
      pharmacologic study of erlotinib in previously treated advanced non-small cell
      lung cancer.
AB  - BACKGROUND: To evaluate the anticancer activity of erlotinib in patients with
      previously treated, advanced non-small cell lung cancer (NSCLC) whose dose is
      increased to that associated with a maximal level of tolerable skin toxicity
      (i.e., target rash (TR)); to characterise the pharmacokinetics (PK) and
      pharmacodynamics (PD) of higher doses of erlotinib. METHODS: Patients initially
      received erlotinib 150 mg per day. The dose was successively increased in each
      patient to that associated with a TR. Anticancer activity was evaluated. Plasma,
      skin, and hair were sampled for PK and PD studies. RESULTS: Erlotinib dose
      escalation to 200-475 mg per day was feasible in 38 (90%) of 42 patients. Twenty
      four (57%) patients developed a TR, but 19 (79%) did so at 150 mg per day. Five
      (12%) patients, all of whom developed a TR, had a partial response. Median
      progression-free survival (PFS) was 2.3 months (95% CI: 1.61, 4.14); median PFS
      was 3.5 months and 1.9 months, respectively, for patients who did and did not
      experience a TR (hazard ratio, 0.51; P=0.051). Neither rash severity nor response
      correlated with erlotinib exposure. CONCLUSION: Intrapatient dose escalation of
      erlotinib does not appreciably increase the propensity to experience a maximal
      level of tolerable skin toxicity, or appear to increase the anticancer activity
      of erlotinib in NSCLC.

PMID- 21878941
TI  - Initial toxicity assessment of ICON6: a randomised trial of cediranib plus
      chemotherapy in platinum-sensitive relapsed ovarian cancer.
AB  - BACKGROUND: Cediranib is a potent oral vascular endothelial growth factor (VEGF)
      signalling inhibitor with activity against all three VEGF receptors. The
      International Collaboration for Ovarian Neoplasia 6 (ICON6) trial was initiated
      based on evidence of single-agent activity in ovarian cancer with acceptable
      toxicity. METHODS: The ICON6 trial is a 3-arm, 3-stage, double-blind, placebo
      controlled randomised trial in first relapse of platinum-sensitive ovarian
      cancer. Patients are randomised (2 : 3 : 3) to receive six cycles of carboplatin
      (AUC5/6) plus paclitaxel (175 mg m(-2)) with either placebo (reference),
      cediranib 20 mg per day, followed by placebo (concurrent), or cediranib 20 mg per
      day, followed by cediranib (concurrent plus maintenance). Cediranib or placebo
      was continued for 18 months or until disease progression. The primary outcome
      measure for stage I was safety, and the blinded results are presented here.
      RESULTS: Sixty patients were included in the stage I analysis. A total of 53
      patients had received three cycles of chemotherapy and 42 patients had completed
      six cycles. In all, 19 out of 60 patients discontinued cediranib or placebo
      during chemotherapy because of adverse events/intercurrent illness (n=9); disease
      progression (n=1); death (n=3); patient decision (n=1); administrative reasons
      (n=1); and multiple reasons (n=4). Grade 3 and 4 toxicity was experienced by 30
      (50%) and 3 (5%) patients, respectively. No gastrointestinal perforations were
      observed. CONCLUSION: The addition of cediranib to platinum-based chemotherapy is
      sufficiently well tolerated to expand the ICON6 trial and progress to stage II.

PMID- 21878943
TI  - Absolute configurations of (-)-hirsutanol A and (-)-hirsutanol C produced by
      Gloeostereum incarnatum.
AB  -  

PMID- 21878944
TI  - Proteomic analysis of mitochondria in APOE transgenic mice and in response to an
      ischemic challenge.
AB  - Apolipoprotein E (APOE)-E4 is associated with a deleterious outcome after
      ischemic brain injury, which may involve abnormal regulation of mitochondrial
      function. We have assessed the mitochondrial proteomic response of APOE-E3 and
      APOE-E4 transgenic mice to transient global ischemic injury in the hippocampus. A
      genotype-dependent increase in ApoE levels in mitochondria was observed after
      ischemia, with APOE-E4 mice showing significantly greater increases than APOE-E3
      mice. Quantitative analysis of the mitochondria-enriched fractions was performed
      using liquid-chromatography mass spectrometry coupled to label-free analysis. Of
      the 1,067 identified proteins, 274 were mitochondria associated. Mitochondrial
      protein expression was significantly different between genotypes under basal
      conditions as well as in response to global ischemia. A total of 12 mitochondrial
      proteins (including respiratory chain proteins NDUFA11, NDUFS3, NDUF5B, ATP5J, as
      well as ETFA, CYB5B, ATP6V1A, HSPA1B, OXR1, GLUL, IARS2, and PHYHIPL) were
      significantly altered with respect to genotype, global ischemia, or their
      interaction (P<0.01). A compelling interactome, created using proteins found to
      be significantly modulated by global ischemia (P<0.05), involved proteins that
      regulate energy production and oxidative stress. Thus, APOE genotype has a
      differential effect on the mitochondrial protein expression in the absence and
      presence of an injury, which may underlie the differing genotype susceptibility.

PMID- 21878945
TI  - The pathologic cascade of cerebrovascular lesions in SHRSP: is erythrocyte
      accumulation an early phase?
AB  - Cerebral small vessel disease (CSVD) is associated with vessel wall changes,
      microbleeds, blood-brain barrier (BBB) disturbances, and reduced cerebral blood
      flow (CBF). As spontaneously hypertensive stroke-prone rats (SHRSP) may be a
      valid model of some aspects of human CSVD, we aimed to identify whether those
      changes occur in definite temporal stages and whether there is an initial
      phenomenon beyond those common vascular alterations. Groups of 51 SHRSP were
      examined simultaneously by histologic (Hematoxylin-Eosin, IgG
      Immunohistochemistry, vessel diameter measurement) and imaging methods (Magnetic
      Resonance Imaging, 201-Thallium-Diethyldithiocarbamate/99m-Technetium-HMPAO
      Single Photon Emission Computed Tomography conducted as pilot study) at different
      stages of age. Vascular pathology in SHRSP proceeds in definite stages, whereas
      an age-dependent accumulation of erythrocytes in capillaries and arterioles
      represents the homogeneous initial step of the disease. Erythrocyte accumulations
      are followed by BBB disturbances and microbleeds, both also increasing with age.
      Microthromboses, tissue infarctions with CBF reduction, and disturbed potassium
      uptake represent the final stage of vascular pathology in SHRSP. Erythrocyte
      accumulations--we parsimoniously interpreted as stases--without cerebral tissue
      damage represent the first step of vascular pathology in SHRSP. If that initial
      phenomenon could be identified in patients, these erythrocyte accumulations might
      be a promising target for implementing prophylactic and therapeutic strategies in
      human CSVD.

PMID- 21878946
TI  - Comparative effects of glucose- and mannitol-induced osmolar stress on blood
      brain barrier function in ovine fetuses and lambs.
AB  - We examined the effects of hyperglycemic hyperosmolality on blood-brain barrier
      (BBB) permeability during development. We hypothesized that the barrier becomes
      more resistant to hyperglycemic hyperosmolality during development, and the
      immature BBB is more resistant to glucose than to mannitol hyperosmolality. We
      quantified the BBB response to hyperosmolality with the blood-to-brain transfer
      constant (K(i)) in immature fetuses, premature, and newborn lambs. K(i) increased
      as a function of increases in osmolality. A segmented regression model described
      the relationship between K(i) and osmolality. At lower osmolalities, changes in
      K(i) were minimal but after a threshold, increases were linear. We examined
      responses of K(i) to hyperglycemic hyperosmolality by comparing the thresholds
      and slopes of the second regression segments. Lower thresholds and steeper slopes
      indicate greater vulnerability to hyperosmolality. Thresholds increased (P<0.05)
      during development in pons and superior colliculus. Thresholds were higher
      (P<0.05) during glucose than mannitol hyperosmolality in thalamus, superior
      colliculus, inferior colliculus and medulla of premature lambs, and in cerebrum
      and cerebellum of newborns. We conclude that BBB permeability increased as a
      function of changes in glucose osmolality, the barrier becomes more resistant to
      glucose hyperosmolality in two brain regions during development, and the barrier
      is more resistant to glucose than to mannitol hyperosmolality in some brain
      regions of premature and newborn lambs.

PMID- 21878947
TI  - Within-subject comparison of [(11)C]-(+)-PHNO and [(11)C]raclopride sensitivity
      to acute amphetamine challenge in healthy humans.
AB  - [(11)C]PHNO is a D(2)/D(3) agonist positron emission tomography radiotracer, with
      higher in vivo affinity for D(3) than for D(2) receptors. As [(11)C]-(+)-PHNO is
      an agonist, its in vivo binding is expected to be more affected by acute
      fluctuations in synaptic dopamine than that of antagonist radiotracers such as
      [(11)C]raclopride. In this study, the authors compared the effects of an oral
      dose of the dopamine releaser amphetamine (0.3 mg/kg) on in vivo binding of
      [(11)C]-(+)-PHNO and [(11)C]raclopride in healthy subjects, using a within
      subjects, counterbalanced, open-label design. In the dorsal striatum, where the
      density of D(3) receptors is negligible and both tracers predominantly bind to
      D(2) receptors, the reduction of [(11)C]-(+)-PHNO binding potential (BP(ND)) was
      1.5 times larger than that of [(11)C]raclopride. The gain in sensitivity
      associated with the agonist [(11)C]-(+)-PHNO implies that ~65% of D(2) receptors
      are in the high-affinity state in vivo. In extrastriatal regions, where [(11)C]
      (+)-PHNO predominantly binds to D(3) receptors, the amphetamine effect on [(11)C]
      (+)-PHNO BP(ND) was even larger, consistent with the higher affinity of dopamine
      for D(3). This study indicates that [(11)C]-(+)-PHNO is superior to
      [(11)C]raclopride for studying acute fluctuations in synaptic dopamine in the
      human striatum. [(11)C]-(+)-PHNO also enables measurement of synaptic dopamine in
      D(3) regions.

PMID- 21878951
TI  - Glomerulonephritis therapy: is there a role for green tea?
AB  - Rapidly progressive glomerulonephritis is the most aggressive form of
      glomerulonephritis with the worst prognosis. The current unspecific
      immunosuppressive therapy with corticosteroids and cytotoxic agents is often
      complicated by severe side effects. Peng and colleagues studied the therapeutic
      potential of the green tea component (-)-epigallocatechin-3-gallate (EGCG) in a
      murine model of immune-mediated glomerulonephritis. Their results indicate that
      EGCG treatment ameliorates renal inflammation, tissue damage, and loss of renal
      function and might therefore represent a novel therapeutic approach for human
      glomerulonephritis.

PMID- 21878952
TI  - L-carnitine: more than just an alternative to glucose as an osmotic agent for
      peritoneal dialysis?
AB  - Glucose toxicity remains a concern for long-term membrane function and metabolic
      side effects in peritoneal dialysis. Partial substitution of L-carnitine as an
      alternative but similarly effective osmotic agent is an attractive proposition,
      and, given once daily with glucose, it achieves equivalent ultrafiltration and
      plasma concentrations that are likely to be safe. The possibility that it can
      counter glucose-mediated injury to the aquaporin pathway, thus enhancing
      ultrafiltration, is an intriguing bonus that requires further study.

PMID- 21878948
TI  - Impact of tissue plasminogen activator on the neurovascular unit: from clinical
      data to experimental evidence.
AB  - About 15 million strokes occur each year worldwide. As the number one cause of
      morbidity and acquired disability, stroke is a major drain on public health-care
      funding, due to long hospital stays followed by ongoing support in the community
      or nursing-home care. Although during the last 10 years we have witnessed a
      remarkable progress in the understanding of the pathophysiology of ischemic
      stroke, reperfusion induced by recombinant tissue-type plasminogen activator (tPA
      Actilyse) remains the only approved acute treatment by the health authorities.
      The objective of the present review is to provide an overview of our present
      knowledge about the impact of tPA on the neurovascular unit during acute ischemic
      stroke.

PMID- 21878953
TI  - The challenges of assessing acute kidney injury in infants.
AB  - Definitions of pediatric acute kidney injury (AKI) use changes of serum
      creatinine. There is a paucity of well-designed studies in infants because of
      creatinine age-dependency. The emerging role of cystatin C as a superior marker
      of renal dysfunction led to a carefully conducted study on AKI in infants by
      Zappitelli et al. This Commentary calls for the development of age-independent
      serum creatinine and estimated glomerular filtration rate z scores.

PMID- 21878954
TI  - Is there a deleterious effect of erythropoietin in end-stage renal disease?
AB  - The use of erythropoiesis-stimulating agents (ESAs) in patients with chronic
      kidney disease has declined as randomized controlled trials have demonstrated
      increased risk of cardiovascular complications and mortality without a marked
      benefit in quality of life. Several studies have suggested that exposure to high
      dosages of ESA, rather than raising of the hemoglobin concentration, explains
      this increased risk. Cotter and colleagues report that exposure to high dosages
      of ESA in patients with diabetes is associated with increased risk.

PMID- 21878955
TI  - Endoscopic treatment of obstructed peritoneal catheter.

PMID- 21878956
TI  - The case: hemolysis and acute renal failure. Babesiosis.

PMID- 21878957
TI  - Association of MTHFR and RFC1 gene polymorphism with hyperhomocysteinemia and its
      modulation by vitamin B12 and folic acid in an Indian population.
AB  - BACKGROUND/OBJECTIVES: Unlike most Western populations, MTHFR 677T is a rare
      allele and a risk factor for a variety of disorders in India. What kind of
      nutritional (environmental) and/or genetic factors could contribute to the
      genetic risk is not known. To assess the incidence of hyperhomocysteinemia and
      its correlation with the polymorphism in homocysteine (Hcy)-pathway genes and
      associated cofactors in the native populations of eastern India.
      SUBJECTS/METHODS: Healthy population from four eastern states of India.
      Genotyping of SNPs, HPLC and chemiluminescence-based assay for homocysteine,
      vitamin B12 and folic acid. RESULTS: Approximately 30% of the population has
      hyperhomocysteinemia (>15 MUmol/lit; hypHcy) with varying frequencies in the four
      states from where samples were collected (n=1426). Polymorphisms of MTR and CBS
      do not affect hypHcy. 677T and 1298C alleles of MTHFR and G80 RFC-1 show
      association with hypHcy. In contrast, RFC-1 80AA is protective even in presence
      of 677T MTHFR. Addition of each mutant allele has an additive effect on Hcy
      level. Vitamin B12 (cofactor in methionine synthesis) clearly modulates the
      genotypic effect on Hcy level. Although frequency of individuals with low folic
      acid is ~11, 49% of the population is vitamin B12 deficient (<220 pg/lit) and has
      a significant negative correlation with Hcy. Individuals with optimum vitamin B12
      and folic acid generally have low Hcy, even in risk genotypes. CONCLUSIONS: One
      of the plausible reasons for susceptibility of individuals with MTHFR C677T in
      the studied population to various disorders is the high frequency of
      hyperhomocysteinemia and vitamin B12 deficiency in the 'healthy population'.
      Apparently, supplementation of vitamin B(12) to this health-impoverished
      community may help lessen the risk of several multifactorial disorders.

PMID- 21878958
TI  - Sex-specific relationships between adiposity and anthropometric measures and
      carotid intima-media thickness in Koreans: the Healthy Twin Study.
AB  - BACKGROUND/OBJECTIVES: Increased adiposity, shorter stature, shorter leg length
      and carotid intima-media thickening are associated with cardiovascular (CV)
      disease. This study aimed to evaluate the sex-specific phenotypic and genetic
      associations between adiposity and anthropometric measures and carotid intima
      media thickness (IMT). SUBJECTS/METHODS: We measured IMT at common carotid artery
      (CCA-IMT), carotid bifurcation and internal carotid artery (ICA-IMT) using B-mode
      ultrasound, and adiposity and anthropometric measures, including body mass index
      (BMI), height, leg length, waist circumference (WC), waist-to-hip ratio and
      percentage of body fat; we also assessed conventional CV risk factors among 706
      Korean adults from the Healthy Twin Study. The associations were analyzed using
      quantitative genetic and linear mixed analyses. RESULTS: In linear mixed
      analyses, BMI and WC had independent associations with the IMT at CCA-IMT and ICA
      IMT and CCA-IMT, respectively, after adjusting for age and conventional CV risk
      factors in men. By comparison, in women, adiposity and anthropometric measures
      were associated with carotid IMT only before adjusting for the covariates. In
      men, there were significant genetic correlations between BMI and CCA-IMT
      (rho(G)=0.32+/-0.11), BMI and ICA-IMT (rho(G)=0.35+/-0.11) and WC and ICA-IMT
      (rho(G)=0.32+/-0.13) after adjusting for covariates, whereas in women the cross
      trait genetic correlations were no longer significant after adjusting for the
      covariates. CONCLUSIONS: In this Korean twins and families, we found sex-specific
      associations between adiposity and anthropometric measures and the IMT at each
      segment of the carotid artery, and BMI and WC in men can be indicators predicting
      carotid intima-media thickening regardless of age and CV risk factors.

PMID- 21878959
TI  - Total dietary antioxidant capacity and lung function in an Italian population: a
      favorable role in premenopausal/never smoker women.
AB  - BACKGROUND/OBJECTIVES: Antioxidant-rich foods may favorably influence lung
      function. We examined possible associations between the total dietary antioxidant
      capacity (TAC) and pulmonary function in a healthy Italian population.
      SUBJECTS/METHODS: Until May 2009, 22,300 persons were randomly recruited from the
      general population in the Moli-sani project. A sample only including healthy
      women (5824) and men (5848) was analyzed. TAC was measured in foods by three
      different assays and the ferric reducing-antioxidant power (FRAP) assay was
      selected as the better indicator of dietary TAC. The European Investigation into
      Cancer and Nutrition Food Frequency Questionnaire was used for dietary
      assessment. The association between quintiles of dietary FRAP and pulmonary
      indexes was assessed using analysis of variance separately for men and women.
      RESULTS: After adjustment for confounders, women in the highest quintile of FRAP
      intake had +39 ml forced expiratory volume in the first second (FEV(1)) and +54
      ml forced vital capacity, compared with those in the lowest quintile (P for trend
      <=0.006). Stratified analysis showed that this relationship only occurred in
      women who were premenopausal/never smokers. In this subgroup, the observed effect
      of higher FRAP intake on FEV(1) was equivalent to an improvement in pulmonary age
      of 3.3 years. In men, all significant associations between pulmonary function and
      TAC were lost after adjustment for confounding. CONCLUSIONS: Dietary TAC may have
      a favorable role in respiratory health, particularly in premenopausal/never
      smoker women.

PMID- 21878960
TI  - Dietary intake of B vitamins and methionine and risk of lung cancer.
AB  - BACKGROUND/OBJECTIVES: B vitamins and related enzymes involved in one-carbon
      metabolism are necessary for DNA replication, DNA repair and regulation of gene
      expression. Disruption of one-carbon mechanism may affect cancer risk. We
      investigated prospectively the relationship between dietary intakes of
      methionine, B vitamins associated with one-carbon metabolism and risk of lung
      cancer. SUBJECTS/METHODS: The Melbourne Collaborative Cohort Study recruited
      41,514 men and women aged 40-69 years between 1990 and 1994. During follow-up of
      14,595 men and 22,451 women for an average of 15 years, we ascertained 348
      incident lung cancers. Dietary intake of B vitamins and methionine was estimated
      from a 121-item food frequency questionnaire. Hazard ratios (HR) and 95%
      confidence intervals (CI) were estimated using Cox regression. RESULTS: In
      current smokers, dietary intake of riboflavin was inversely associated with lung
      cancer risk (HR=0.53; 95% CI: 0.29-0.94, fifth versus first quintile; P-linear
      trend=0.01). No associations were found for former or never smokers or for
      dietary intake of any of the other B vitamins or methionine. CONCLUSION: Overall,
      we found little evidence of an association between B vitamins or methionine and
      lung cancer risk. The weak inverse association between riboflavin and lung cancer
      risk in current smokers needs further investigation.

PMID- 21878962
TI  - Keeping ZFNs on target.

PMID- 21878961
TI  - Understanding the contribution of synonymous mutations to human disease.
AB  - Synonymous mutations - sometimes called 'silent' mutations - are now widely
      acknowledged to be able to cause changes in protein expression, conformation and
      function. The recent increase in knowledge about the association of genetic
      variants with disease, particularly through genome-wide association studies, has
      revealed a substantial contribution of synonymous SNPs to human disease risk and
      other complex traits. Here we review current understanding of the extent to which
      synonymous mutations influence disease, the various molecular mechanisms that
      underlie these effects and the implications for future research and biomedical
      applications.

PMID- 21878964
TI  - Aneuploidy stokes the fire.

PMID- 21878963
TI  - The evolutionary origin of orphan genes.
AB  - Gene evolution has long been thought to be primarily driven by duplication and
      rearrangement mechanisms. However, every evolutionary lineage harbours orphan
      genes that lack homologues in other lineages and whose evolutionary origin is
      only poorly understood. Orphan genes might arise from duplication and
      rearrangement processes followed by fast divergence; however, de novo evolution
      out of non-coding genomic regions is emerging as an important additional
      mechanism. This process appears to provide raw material continuously for the
      evolution of new gene functions, which can become relevant for lineage-specific
      adaptations.

PMID- 21878965
TI  - A call to reform the taxonomy of human disease.
AB  - A coordinated effort to incorporate advances in the understanding of the
      molecular and genomic variations in common diseases, such as hypertension, into
      their diagnosis and treatment could transform drug development and medicine.

PMID- 21878966
TI  - Reliability of 'new drug target' claims called into question.

PMID- 21878967
TI  - Diabetes field cautiously upbeat despite possible setback for leading SGLT2
      inhibitor.

PMID- 21878969
TI  - Deal watch: Bristol-Myers Squibb invests in cancer antibody that targets the
      innate immune system.

PMID- 21878970
TI  - Trial watch: ERBB2 dimerization inhibitor meets end point in breast cancer trial.

PMID- 21878971
TI  - DNA patent decision leaves questions for diagnostics.

PMID- 21878972
TI  - Joe selby. Interview by Asher Mullard.

PMID- 21878973
TI  - Identifying R&D outliers.

PMID- 21878975
TI  - Diabetes: Mobilizing regulatory T cells against type 1 diabetes.

PMID- 21878974
TI  - Belatacept.

PMID- 21878976
TI  - Anticancer Drugs: Selective oxycution?

PMID- 21878977
TI  - Vaccines: Structure-based design.

PMID- 21878978
TI  - Metabolic disease: Turning 'bad' fat into 'good'.

PMID- 21878979
TI  - Cognitive impairment: Rescuing age-related memory loss.

PMID- 21878981
TI  - Minimum information about a bioactive entity (MIABE).
AB  - Bioactive molecules such as drugs, pesticides and food additives are produced in
      large numbers by many commercial and academic groups around the world. Enormous
      quantities of data are generated on the biological properties and quality of
      these molecules. Access to such data - both on licensed and commercially
      available compounds, and also on those that fail during development - is crucial
      for understanding how improved molecules could be developed. For example,
      computational analysis of aggregated data on molecules that are investigated in
      drug discovery programmes has led to a greater understanding of the properties of
      successful drugs. However, the information required to perform these analyses is
      rarely published, and when it is made available it is often missing crucial data
      or is in a format that is inappropriate for efficient data-mining. Here, we
      propose a solution: the definition of reporting guidelines for bioactive entities
      - the Minimum Information About a Bioactive Entity (MIABE) - which has been
      developed by representatives of pharmaceutical companies, data resource providers
      and academic groups.

PMID- 21878984
TI  - Comparison of biometrical models for joint linkage association mapping.
AB  - Joint linkage association mapping (JLAM) combines the advantages of linkage
      mapping and association mapping, and is a powerful tool to dissect the genetic
      architecture of complex traits. The main goal of this study was to use a cross
      validation strategy, resample model averaging and empirical data analyses to
      compare seven different biometrical models for JLAM with regard to the correction
      for population structure and the quantitative trait loci (QTL) detection power.
      Three linear models and four linear mixed models with different approaches to
      control for population stratification were evaluated. Models A, B and C were
      linear models with either cofactors (Model-A), or cofactors and a population
      effect (Model-B), or a model in which the cofactors and the single-nucleotide
      polymorphism effect were modeled as nested within population (Model-C). The mixed
      models, D, E, F and G, included a random population effect (Model-D), or a random
      population effect with defined variance structure (Model-E), a kinship matrix
      defining the degree of relatedness among the genotypes (Model-F), or a kinship
      matrix and principal coordinates (Model-G). The tested models were conceptually
      different and were also found to differ in terms of power to detect QTL. Model-B
      with the cofactors and a population effect, effectively controlled population
      structure and possessed a high predictive power. The varying allele substitution
      effects in different populations suggest as a promising strategy for JLAM to use
      Model-B for the detection of QTL and then to estimate their effects by applying
      Model-C.

PMID- 21878982
TI  - Targeting cancer metabolism: a therapeutic window opens.
AB  - Genetic events in cancer activate signalling pathways that alter cell metabolism.
      Clinical evidence has linked cell metabolism with cancer outcomes. Together,
      these observations have raised interest in targeting metabolic enzymes for cancer
      therapy, but they have also raised concerns that these therapies would have
      unacceptable effects on normal cells. However, some of the first cancer therapies
      that were developed target the specific metabolic needs of cancer cells and
      remain effective agents in the clinic today. Research into how changes in cell
      metabolism promote tumour growth has accelerated in recent years. This has
      refocused efforts to target metabolic dependencies of cancer cells as a selective
      anticancer strategy.

PMID- 21878983
TI  - How closely does genetic diversity in finite populations conform to predictions
      of neutral theory? Large deficits in regions of low recombination.
AB  - Levels of genetic diversity in finite populations are crucial in conservation and
      evolutionary biology. Genetic diversity is required for populations to evolve and
      its loss is related to inbreeding in random mating populations, and thus to
      reduced population fitness and increased extinction risk. Neutral theory is
      widely used to predict levels of genetic diversity. I review levels of genetic
      diversity in finite populations in relation to predictions of neutral theory.
      Positive associations between genetic diversity and population size, as predicted
      by neutral theory, are observed for microsatellites, allozymes, quantitative
      genetic variation and usually for mitochondrial DNA (mtDNA). However, there are
      frequently significant deviations from neutral theory owing to indirect selection
      at linked loci caused by balancing selection, selective sweeps and background
      selection. Substantially lower genetic diversity than predicted under neutrality
      was found for chromosomes with low recombination rates and high linkage
      disequilibrium (compared with 'normally' recombining chromosomes within species
      and adjusted for different copy numbers and mutation rates), including W (median
      100% lower) and Y (89% lower) chromosomes, dot fourth chromosomes in Drosophila
      (94% lower) and mtDNA (67% lower). Further, microsatellite genetic and allelic
      diversity were lost at 12 and 33% faster rates than expected in populations
      adapting to captivity, owing to widespread selective sweeps. Overall, neither
      neutral theory nor most versions of the genetic draft hypothesis are compatible
      with all empirical results.

PMID- 21878985
TI  - Hybrid incompatibilities in the parasitic wasp genus Nasonia: negative effects of
      hemizygosity and the identification of transmission ratio distortion loci.
AB  - The occurrence of hybrid incompatibilities forms an important stage during the
      evolution of reproductive isolation. In early stages of speciation, males and
      females often respond differently to hybridization. Haldane's rule states that
      the heterogametic sex suffers more from hybridization than the homogametic sex.
      Although haplodiploid reproduction (haploid males, diploid females) does not
      involve sex chromosomes, sex-specific incompatibilities are predicted to be
      prevalent in haplodiploid species. Here, we evaluate the effect of sex/ploidy
      level on hybrid incompatibilities and locate genomic regions that cause increased
      mortality rates in hybrid males of the haplodiploid wasps Nasonia vitripennis and
      Nasonia longicornis. Our data show that diploid F(1) hybrid females suffer less
      from hybridization than haploid F(2) hybrid males. The latter not only suffer
      from an increased mortality rate, but also from behavioural and spermatogenic
      sterility. Genetic mapping in recombinant F(2) male hybrids revealed that the
      observed hybrid mortality is most likely due to a disruption of cytonuclear
      interactions. As these sex-specific hybrid incompatibilities follow predictions
      based on Haldane's rule, our data accentuate the need to broaden the view of
      Haldane's rule to include species with haplodiploid sex determination, consistent
      with Haldane's original definition.

PMID- 21878986
TI  - Novel measures of linkage disequilibrium that correct the bias due to population
      structure and relatedness.
AB  - Among the several linkage disequilibrium measures known to capture different
      features of the non-independence between alleles at different loci, the most
      commonly used for diallelic loci is the r(2) measure. In the present study, we
      tackled the problem of the bias of r(2) estimate, which results from the sample
      structure and/or the relatedness between genotyped individuals. We derived two
      novel linkage disequilibrium measures for diallelic loci that are both extensions
      of the usual r(2) measure. The first one, r(S)(2), uses the population structure
      matrix, which consists of information about the origins of each individual and
      the admixture proportions of each individual genome. The second one, r(V)(2),
      includes the kinship matrix into the calculation. These two corrections can be
      applied together in order to correct for both biases and are defined either on
      phased or unphased genotypes.We proved that these novel measures are linked to
      the power of association tests under the mixed linear model including structure
      and kinship corrections. We validated them on simulated data and applied them to
      real data sets collected on Vitis vinifera plants. Our results clearly showed the
      usefulness of the two corrected r(2) measures, which actually captured 'true'
      linkage disequilibrium unlike the usual r(2) measure.

PMID- 21878988
TI  - The five 'W's of transport.

PMID- 21878987
TI  - Urinary arsenic species, toenail arsenic, and arsenic intake estimates in a
      Michigan population with low levels of arsenic in drinking water.
AB  - The large disparity between arsenic concentrations in drinking water and urine
      remains unexplained. This study aims to evaluate predictors of urinary arsenic in
      a population exposed to low concentrations (<=50 MUg/l) of arsenic in drinking
      water. Urine and drinking water samples were collected from a subsample (n=343)
      of a population enrolled in a bladder cancer case-control study in southeastern
      Michigan. Total arsenic in water and arsenic species in urine were determined
      using ICP-MS: arsenobetaine (AsB), arsenite (As[III]), arsenate (As[V]),
      methylarsenic acid (MMA[V]), and dimethylarsenic acid (DMA[V]). The sum of
      As[III], As[V], MMA[V], and DMA[V] was denoted as SumAs. Dietary information was
      obtained through a self-reported food intake questionnaire. Log(10)-transformed
      drinking water arsenic concentration at home was a significant (P<0.0001)
      predictor of SumAs (R(2)=0.18). Associations improved (R(2)=0.29, P<0.0001) when
      individuals with less than 1 MUg/l of arsenic in drinking water were removed and
      further improved when analyses were applied to individuals who consumed amounts
      of home drinking water above the median volume (R(2)=0.40, P<0.0001). A separate
      analysis indicated that AsB and DMA[V] were significantly correlated with fish
      and shellfish consumption, which may suggest that seafood intake influences
      DMA[V] excretion. The Spearman correlation between arsenic concentration in
      toenails and SumAs was 0.36 and between arsenic concentration in toenails and
      arsenic concentration in water was 0.42. Results show that arsenic exposure from
      drinking water consumption is an important determinant of urinary arsenic
      concentrations, even in a population exposed to relatively low levels of arsenic
      in drinking water, and suggest that seafood intake may influence urinary DMA[V]
      concentrations.

PMID- 21878990
TI  - Protein export at the ER: loading big collagens into COPII carriers.
AB  - COPII vesicles mediate the export of secretory cargo from endoplasmic reticulum
      (ER) exit sites. However, of 60-90 nm diameter COPII vesicles are too small to
      accommodate secreted molecules such as the collagens. The ER exit site-located
      proteins TANGO1 and cTAGE5 are required for the transport of collagens and
      therefore provide a means to understand the export of big cargo and the mechanism
      of COPII carrier size regulation commensurate with cargo dimensions.

PMID- 21878989
TI  - Ran-dependent nuclear export mediators: a structural perspective.
AB  - Nuclear export is an essential eukaryotic activity. It proceeds through nuclear
      pore complexes (NPCs) and is mediated by soluble receptors that shuttle between
      nucleus and cytoplasm. RanGTPase-dependent export mediators (exportins)
      constitute the largest class of these carriers and are functionally highly
      versatile. All of these exportins load their substrates in response to RanGTP
      binding in the nucleus and traverse NPCs as ternary RanGTP-exportin-cargo
      complexes to the cytoplasm, where GTP hydrolysis leads to export complex
      disassembly. The different exportins vary greatly in their substrate range.
      Recent structural studies of both protein- and RNA-specific exporters have
      illuminated how exportins bind their cargoes, how Ran triggers cargo loading and
      how export complexes are disassembled in the cytoplasm. Here, we review the
      current state of knowledge and highlight emerging principles as well as
      prevailing questions.

PMID- 21878992
TI  - Let's go bananas: revisiting the endocytic BAR code.
AB  - Against the odds of membrane resistance, members of the BIN/Amphiphysin/Rvs (BAR)
      domain superfamily shape membranes and their activity is indispensable for a
      plethora of life functions. While crystal structures of different BAR dimers
      advanced our understanding of membrane shaping by scaffolding and hydrophobic
      insertion mechanisms considerably, especially life-imaging techniques and loss-of
      function studies of clathrin-mediated endocytosis with its gradually increasing
      curvature show that the initial idea that solely BAR domain curvatures determine
      their functions is oversimplified. Diagonal placing, lateral lipid-binding modes,
      additional lipid-binding modules, tilde shapes and formation of macromolecular
      lattices with different modes of organisation and arrangement increase
      versatility. A picture emerges, in which BAR domain proteins create
      macromolecular platforms, that recruit and connect different binding partners and
      ensure the connection and coordination of the different events during the
      endocytic process, such as membrane invagination, coat formation, actin
      nucleation, vesicle size control, fission, detachment and uncoating, in time and
      space, and may thereby offer mechanistic explanations for how coordination,
      directionality and effectiveness of a complex process with several steps and key
      players can be achieved.

PMID- 21878991
TI  - Endosome maturation.
AB  - Being deeply connected to signalling, cell dynamics, growth, regulation, and
      defence, endocytic processes are linked to almost all aspects of cell life and
      disease. In this review, we focus on endosomes in the classical endocytic
      pathway, and on the programme of changes that lead to the formation and
      maturation of late endosomes/multivesicular bodies. The maturation programme
      entails a dramatic transformation of these dynamic organelles disconnecting them
      functionally and spatially from early endosomes and preparing them for their
      unidirectional role as a feeder pathway to lysosomes.

PMID- 21878993
TI  - Regulation of developmental intercellular signalling by intracellular
      trafficking.
AB  - Universal trafficking components within the cell can be recruited to coordinate
      and regulate the developmental signalling cascades. We will present ways in which
      the intracellular trafficking machinery is used to affect and modulate the
      outcome of signal transduction in developmental contexts, thus regulating
      multicellular development. Each of the signalling components must reach its
      proper intracellular destination, in a form that is properly folded and modified.
      In many instances, the ability to bring components together or segregate them
      into distinct compartments within the cell actually provides the switch mechanism
      to turn developmental signalling pathways on or off. The review will begin with a
      focus on the signal-sending cells, and the ways in which ligand trafficking can
      impinge on the signalling outcome, via processing, endocytosis and recycling. We
      will then turn to the signal-receiving cell, and discuss mechanisms by which
      endocytosis can affect the spatial features of the signal, and the
      compartmentalization of components downstream to the receptor.

PMID- 21878997
TI  - The road not taken: new destinations for yeast mRNAs on the move.

PMID- 21878995
TI  - Mechanisms of dendritic mRNA transport and its role in synaptic tagging.
AB  - The localization of RNAs critically contributes to many important cellular
      processes in an organism, such as the establishment of polarity, asymmetric
      division and migration during development. Moreover, in the central nervous
      system, the local translation of mRNAs is thought to induce plastic changes that
      occur at synapses triggered by learning and memory. Here, we will critically
      review the physiological functions of well-established dendritically localized
      mRNAs and their associated factors, which together form ribonucleoprotein
      particles (RNPs). Second, we will discuss the life of a localized transcript from
      transcription in the nucleus to translation at the synapse and introduce the
      concept of the 'RNA signature' that is characteristic for each transcript.
      Finally, we present the 'sushi belt model' of how localized RNAs within neuronal
      RNPs may dynamically patrol multiple synapses rather than being anchored at a
      single synapse. This new model integrates our current understanding of synaptic
      function ranging from synaptic tagging and capture to functional and structural
      reorganization of the synapse upon learning and memory.

PMID- 21878994
TI  - Coupling viruses to dynein and kinesin-1.
AB  - It is now clear that transport on microtubules by dynein and kinesin family
      motors has an important if not critical role in the replication and spread of
      many different viruses. Understanding how viruses hijack dynein and kinesin
      motors using a limited repertoire of proteins offers a great opportunity to
      determine the molecular basis of motor recruitment. In this review, we discuss
      the interactions of dynein and kinesin-1 with adenovirus, the alpha herpes
      viruses: herpes simplex virus (HSV1) and pseudorabies virus (PrV), human
      immunodeficiency virus type 1 (HIV-1) and vaccinia virus. We highlight where the
      molecular links to these opposite polarity motors have been defined and discuss
      the difficulties associated with identifying viral binding partners where the
      basis of motor recruitment remains to be established. Ultimately, studying
      microtubule-based motility of viruses promises to answer fundamental questions as
      to how the activity and recruitment of the dynein and kinesin-1 motors are
      coordinated and regulated during bi-directional transport.

PMID- 21878996
TI  - Intercellular and systemic movement of RNA silencing signals.
AB  - In most eukaryotes, double-stranded RNA is processed into small RNAs that are
      potent regulators of gene expression. This gene silencing process is known as RNA
      silencing or RNA interference (RNAi) and, in plants and nematodes, it is
      associated with the production of a mobile signal that can travel from cell-to
      cell and over long distances. The sequence-specific nature of systemic RNA
      silencing indicates that a nucleic acid is a component of the signalling complex.
      Recent work has shed light on the mobile RNA species, the genes involved in the
      production and transport of the signal. This review discusses the advances in
      systemic RNAi and presents the current challenges and questions in this rapidly
      evolving field.

PMID- 21878999
TI  - Microbial reduction in the NICU: seeing the light.

PMID- 21879000
TI  - Evaluating neonatal hyperbilirubinemia in late preterm Hispanic twins led to the
      diagnosis of hereditary spherocytosis in them, and in their sibling and in their
      mother.
AB  - We identified four cases of hereditary spherocytosis (HS) in one Utah family,
      originally from Southwestern Mexico. The index cases were twin girls born at 35
      weeks gestation, in whom the combination of hyperbilirubinemia, reticulocytosis
      and elevated mean corpuscular hemoglobin concentration (MCHC) led to studies that
      confirmed the diagnosis of HS. Scleral icterus in their 4-year-old sibling and in
      their mother led to the diagnosis of HS in them as well. Although much less
      commonly reported in Hispanic neonates than in those of Northern European
      ancestry, HS does occur among Hispanic neonates and can contribute to significant
      neonatal hyperbilirubinemia. These cases are consistent with our earlier report,
      which identified an MCHC cutoff of >36 as suggestive of further evaluation for
      HS.

PMID- 21879001
TI  - Atypical presentation of a lacrimal duct cyst.

PMID- 21879002
TI  - Lethality begets lethality.

PMID- 21879004
TI  - Environmental burden of acute respiratory infection and pneumonia due to indoor
      smoke in Dhading.
AB  - BACKGROUND: ARI and pneumonia is one of the major public health problems in Nepal
      which always ranks highest position among the top ten diseases. One of the risk
      factor of ARI and pneumonia is indoor smoke from kitchen where primary source of
      cooking is solid biomass fuel. This study was carried out in order to estimate
      the burden of ARI and pneumonia due to indoor smoke. ARI and pneumonia was chosen
      as it is one of the significant public health problem among under five children
      in Nepal and responsible for high number of premature deaths. METHODS: A cross
      sectional study was conducted in Dhading district. Multistage cluster sampling
      technique was used for data collection considering ward as a cluster. The
      environmental burden of ARI and pneumonia due to indoor smoke was calculated
      using the WHO Environmental Burden of Disease Series. RESULTS: About 87 percent
      of households were using solid biomass fuel as a primary source of fuel. The
      under five children exposed to solid fuel use was 41313. The total 1284
      Disability Adjusted Life Years were lost due to ARI and pneumonia and about 50
      percent of it was attributed by Indoor smoke in household. CONCLUSIONS: The solid
      biomass fuel was primary source of energy for cooking in Dhading district which
      is attributing about 50 percent of burden of ARI and pneumonia among under five
      children.

PMID- 21879005
TI  - Impact of first aid training in management of snake bite victims in Madi valley.
AB  - BACKGROUND: Tropical lowland on Nepal is at full of risk to snake bite. The snake
      bite mortality is due to lack of awareness about proper management of victims.
      The study aims to assess the change in the pattern of management of snake bite
      victims after first aid training. METHODS: A retrospective study was done from
      October 2007 to October 2008 among 43 snake bite victims in rural Madi valley
      comprising of 4 village development committees where first aid training was
      conducted one year before. RESULTS: Only 26% of the snake bite victims approached
      traditional healer before arriving at the heath facility. The case fatality rate
      dropped to 22% after venomous snake bite. Pressure Immobilization bandaging and
      local compression pad immobilization technique was used by 56% who went to the
      health facility. Mean duration for reaching health facility was 61.51+/-33.55
      minutes. Common places of bite were field 16 (37.2%), Indoor 6 (14%), while
      sleeping 6 (14%), and yard 6 (14%). Lower extremity bites were 32 (74.4%), upper
      extremity 8 (18.6%) and head 3 (7%). Bicycle was the commonest mode of transport
      22 (51%) followed by ambulance 9(27.9%) and Motorcycle 6 (11%). CONCLUSIONS:
      First aid training changes the attitude of the people in management of snake bite
      victims and is one of the effective ways in decreasing mortality. Nationwide
      campaigning should be done especially at snake bite prone area about the proper
      first aid technique to improve the awareness level of the general population.

PMID- 21879006
TI  - Utilization pattern of health care services at village level.
AB  - BACKGROUND: Primary health care service is basic essential health care. Due to
      lack of access to quality health care services, many rural people suffer from
      various health related problems. The objective of this study was to assess how
      health care services are utilized by beneficiaries in two different villages in
      Dhanusha district of Nepal. METHODS: A descriptive cross sectional study was
      conducted in two Village Development Committees with sixty four households
      selected randomly from January 1, to February 27, 2008. RESULTS: The study shows
      that 48 and 21 percent of population were utilizing local available health
      services respectively within and beyond 2 km from the health facility .It
      revealed that distance was significant indicator for utilization of health
      services. Study also shows that those in VDC 1 had availed maximum (67%) service
      of trained man power for delivery as compared to those in VDC 2, (20%) where most
      (80%) of deliveries were conducted by relatives and neighbours, the difference
      was significant. CONCLUSIONS: Distance from the heath services is an important
      factor for utilisation of health resources. The utilisation of health facility
      was satisfactory but the quality of services were not satisfactory.

PMID- 21879007
TI  - Substance use among third year medical students of Nepal.
AB  - BACKGROUND: Substance use is very rampant in a developing country like Nepal.
      Unfortunately, medical field is not exempt from it either. Substance use among
      medical students and doctors not only reduces their efficiency at present but
      also increases their DALY on long term. The main objectives of the study were to
      assess the prevalence of substance use among medical student and to find out
      whether substance use started before or after joining the medical school.
      METHODS: The study design employed for the research was descriptive cross
      sectional. A structured questionnaire about current use of tobacco, alcohol and
      marijuana was used to collect the data from third year students from eight
      medical and one dental college from across the country having 2006 batch.
      RESULTS: The overall response rate was 74.12% (N=510). Among those who responded,
      prevalence of substance use was 49.6%, of which 38.2% were Nepalese nationals and
      11.4% were foreign nationals and 39% were male and 10.6% female. Alcohol based
      product users were 52.3%, tobacco based product users were 55% and marijuana
      users were 65.7% and all started using them after joining the medical school.
      CONCLUSIONS: Almost half of the respondents were involved in some sort of
      substance use and more than half of those using started after joining medical
      school. Hence if proper measures are taken to address this then its prevalence
      can be significantly reduced if not eliminated completely.

PMID- 21879008
TI  - Intrauterine condom tamponade in management of post partum haemorrhage.
AB  - BACKGROUND: Uterine tamponade is often used to control post partum hemorrhage.
      Among various methods, condom Foley's catheter tamponade is simple, easy to use
      and is believed to be effective. The study evaluates outcome of condom Foley's
      catheter tamponade. METHODS: In this prespective observational study, condom
      tamponade was applied to fourteen cases with varying degrees of PPH, not
      controlled with pharmacologic measures. The efficacy on control of bleeding was
      assessed along with the total amount of blood loss and any complications.
      RESULTS: The condom tamponade stopped bleeding in all the cases. Average amount
      of blood loss was 1221 ml. No complications were noted. CONCLUSIONS: Thus, condom
      tamponade is an effective method to control intractable PPH. It's simple and does
      not require expertise to use, so, it can have a wide application even in resource
      poor settings.

PMID- 21879009
TI  - Healthcare liquid waste management.
AB  - BACKGROUND: The management of healthcare liquid waste is an overlooked problem in
      Nepal with stern repercussions in terms of damaging the environment and affecting
      the health of people. This study was carried out to explore the healthcare liquid
      waste management practices in Kathmandu based central hospitals of Nepal.
      METHODS: A descriptive prospective study was conducted in 10 central hospitals of
      Kathmandu during the period of May to December 2008. Primary data were collected
      through interview, observation and microbiology laboratory works and secondary
      data were collected by records review. For microbiological laboratory works,waste
      water specimens cultured for the enumeration of total viable counts using
      standard protocols. RESULTS: Evidence of waste management guidelines and
      committees for the management of healthcare liquid wastes could not be found in
      any of the studied hospitals. Similarly, total viable counts heavily exceeded the
      standard heterotrophic plate count (p=0.000) with no significant difference in
      such counts in hospitals with and without treatment plants (p=0.232).
      CONCLUSIONS: Healthcare liquid waste management practice was not found to be
      satisfactory. Installation of effluent treatment plants and the development of
      standards for environmental indicators with effective monitoring, evaluation and
      strict control via relevant legal frameworks were realized.

PMID- 21879010
TI  - Safety and efficacy of misoprostol for induction of labour.
AB  - BACKGROUND: Induction of labour is widely carried over the world in cases where
      continuation of pregnancy is hazardous to mother or fetus. Varieties of
      techniques are available for induction of labour. Prostaglandin is one of the
      most effective means for achieving cervical ripening and induction of labour.
      This study was carried out to see safety and effectiveness of Misoprostol for
      induction of labour. METHODS: This prospective study was carried out at Kathmandu
      University Hospital, Dhulikhel from Jan 2008 to Aug 2009. A total of 70 patients
      were included in this study. All patients received 50 MUg of Misoprostol in the
      posterior fornix with maximum dose up to 3 doses at interval of 6 hours. Bishops
      scoring was reviewed each time before application of Misoprostol. When favourable
      cervix along with good uterine contraction is noted then augmentation with
      Oxytocinon was done holding Misoprostol. The measures used for the analysis of
      effectiveness and safety of Misoprostol were change in bishop score, total dose
      required, need for augmentation, side effects, duration of first, second and
      third stages of labour, duration from induction till delivery, mode of delivery
      and neonatal outcome. The primary outcome measures were induction to delivery
      interval and caesarean section rate. RESULTS: Out of 70 patients, 21 (30%)
      required augmentation. Among 70 patients, 46 (65%) underwent normal delivery, 6
      (8.6%) underwent instrumental delivery and 18 (25%) patients underwent cesarean
      section for various indications (p=0.00). Total 31 (44%) patients delivered
      within 10 hours of induction, 16 (22%) within 15 hours and 4 (4.7%) took more
      than 18 hours. Duration of second stage of labour was also found to be shortened
      with use of Misoprostol for induction of labour. Duration of second stage of
      labour was less than 30 minutes in 42 (60%) cases and more than 30 minutes in 9
      (17%) cases. CONCLUSIONS: Misoprostol is an effective cervical ripening agent
      with favorable outcome and comparable with other inducing agents.

PMID- 21879011
TI  - Primary salivary gland tumors in eastern Nepal tertiary care hospital.
AB  - BACKGROUND: The knowledge of the distribution and pattern of salivary gland
      tumors in the tertiary care center can provide overview of the disease pattern in
      the region. It also helps in planning the strategies to treat the disease and
      launch the awareness program in the community to this largely curable disease.
      METHODS: A retrospective observational study of all the salivary gland tumors
      treated in the department of Otolaryngology, B. P. Koirala Institute of Health
      Sciences during April 2004 to March 2009 was done. Age, sex, presenting features,
      radiological findings, histopathological type of the tumor and type of surgery
      were recorded and descriptive analysis was done to calculate frequencies,
      percentage and their relations. RESULTS: Out of total 51 cases, 81% (n=41) were
      benign and 19% (n=10) malignant tumors. Male to female ratio was 1:2.1. Mean age
      for benign and malignant tumors were 32.3 and 46.5 years respectively. Parotid
      tumor outnumbered all other sites comprising 69%, followed by submandiibular 18%
      and minor glands 13%. Pleomorphic adenoma was the commonest tumor (76%) of all
      primary salivary gland tumors. Benign to malignant tumor ratio of parotid,
      submandibular and minor glands were 6:1, 3.5:1 and 1.3:1 respectively. Adenoid
      cystic carcinoma (40%) and mucoepidermoid carcinoma (30%) were commonest
      malignant tumors. CONCLUSIONS: The principal site for salivary gland tumors in
      eastern Nepal population was the parotid and the pleomorphic adenoma outnumbered
      all other tumors. Most of the cases in both benign and malignant group presented
      with painless lump often misleading the gravity of disease.

PMID- 21879012
TI  - Maternal and infant mortality in Mahottari district of Nepal.
AB  - BACKGROUND: Reducing maternal mortality by three quarters and under-five
      mortality by two-thirds between 1990 and 2015 are the targets of UN Millennium
      Development Goals as well as of the national safe motherhood programme of Nepal.
      This study was undertaken by Nepal Health Research Council mainly to identify the
      maternal and infant mortalities in Mahottari district. METHODS: A descriptive
      observational study was carried out of maternal and child death over two year
      period before the time of survey was carried out in eleven VDCs of Mahottari
      District and two wards of the Jaleshwor municipality. Data were collected in
      three stages: first, FCHVs collected the information regarding birth, maternal
      and infant death, which were cross-checked later. RESULTS: Maternal mortality
      ratio was estimated at 380 per 100,000 live births, and early neonatal mortality
      rate, neonatal mortality rate and infant mortality rate were found 32, 39 and 52
      per 1,000 live births respectively. The highest deaths in infants were among
      Dalits, whereas it was among Muslims for maternal mortality. All maternal deaths
      occurred at a distance of more than 2 hours. Male-to-female ratio for infant
      mortality was 1:3. The major cause of maternal deaths was post-partum
      haemorrhage, while it was sepsis among infant deaths. CONCLUSIONS: Both maternal
      mortality ratio and infant mortality rate of the district were higher than the
      national average and appeared commensurate with the socio-economic status and
      health facilities of the district when compared with another similar Terai
      district of Bara.

PMID- 21879013
TI  - Limitations of clinico-histopathological correlation of skin biopsies in leprosy.
AB  - BACKGROUND: Skin biopsies play an important role in diagnosing and classifying
      different types of leprosy. The aim of this study was to analyse different
      histologic types of leprosy, to correlate histopathological diagnosis with
      clinical diagnosis, to study the uniformity of clinical and histological findings
      in the diagnosis of leprosy and to evaluate difficulties faced during
      clinicopathological correlation according to Ridley- Jopling classification due
      to inadequacy of data provided. METHODS: This is a retrospective study of all
      skin biopsies reported from Department of Pathology of Tribhuvan University
      Teaching Hospital from 14 April 2007 to 13 April 2009, for which leprosy was the
      diagnosis or was strongly suspected on histopathology. RESULTS: Out of 40 cases
      included, 33 were males and seven were females. Tuberculoid leprosy was the most
      common type comprising 23 /40 cases (57.5%). In 18/ 40 cases (45%), clinical
      diagnosis was leprosy. Only in three, leprosy was classified according to Ridley
      Jopling criteria clinically. Thus clinicopathological correlation according to
      Ridley-Jopling criteria could not be done. Histopathological reporting lacked
      uniformity too. In 13/40 reports (32.5%), exact location of granuloma, presence
      or absence of Grenz zone and enroachment of epidermis by granuloma was not
      mentioned. None mentioned the number and distribution of lymphocytes or relative
      proportion of epithelioid cells and foamy histiocytes. Results: Out of 40 cases
      included, 33 were males and seven were females. Tuberculoid leprosy was the most
      common type comprising 23 /40 cases (57.5%). In 18/ 40 cases (45%), clinical
      diagnosis was leprosy. Only in three, leprosy was classified according to Ridley
      Jopling criteria clinically. Thus clinicopathological correlation according to
      Ridley-Jopling criteria could not be done. Histopathological reporting lacked
      uniformity too. In 13/40 reports (32.5%), exact location of granuloma, presence
      or absence of Grenz zone and enroachment of epidermis by granuloma was not
      mentioned. None mentioned the number and distribution of lymphocytes or relative
      proportion of epithelioid cells and foamy histiocytes. CONCLUSIONS:
      Histopathological diagnosis of leprosy did not correlated with clinical diagnosis
      significantly. Uniformity was not seen in the clinical or histopathological
      informations provided making it difficult to conduct retrospective clinico
      pathological correlation.

PMID- 21879014
TI  - Drug resistant cases of tuberculosis in directly observed treatment short course.
AB  - BACKGROUND: Resistance of Mycobacterium tuberculosis to antituberculous drugs has
      emerged as a major public health threat. The objective of this study was to
      determine Multi Drug Resistance cases of tuberculosis in Directly Observed
      Treatment Short Course program of Nepal. METHODS: The sputum samples collected
      and culture on Lowenstein Jensen media followed by biochemical test. All the
      isolates antibiotic sensitivity test performed on medium by proportion method.
      RESULTS: Tuberculosis was most commonly found in economically active age group
      (21-50 years). All the isolates of pulmonary tuberculosis were found to be M.
      tuberculosis. A Multi-drug resistant case of tuberculosis primary and acquired in
      Directly Observed Treatment Short Course Program of Nepal was found (3.6%). Out
      of 460 untreated cases, 9 (1.9%) cases were found to be MDR and among 90
      previously treated cases 11 (12.2%) were found to be MDR. Multi drug resistant
      cases of tuberculosis were found most commonly in productive age group (21-30).
      The incidence of tuberculosis was found higher in male than in female. But multi
      drug resistant M. tuberculosis cases equally affected both the gender. Majority
      of the MDR cases found higher number of M. tuberculosis in their sputum.
      CONCLUSIONS: The above study showed that drug resistant cases of tuberculosis in
      DOTS program of Nepal was found higher. To reduce the drug resistance, before
      starting chemotherapy antibiotic sensitivity test should be performed.

PMID- 21879015
TI  - Scenario of extrapulmonary tuberculosis in a tertiary care center.
AB  - BACKGROUND: Tuberculosis is a worldwide disease and one of the major health
      problems of Nepal. Extrapulmonary tuberculosis is increasing all over the world.
      The main aim of this study was to assess the frequency of extrapulmonary
      tuberculosis in various organ systems of the body and to assess the pattern of
      disease in different age groups and gender. METHODS: This observational
      retrospective study was carried out from December 2003 to October 2009 at the
      Department of Pathology, Kathmandu University Hospital, Kavre, Nepal. A total of
      259 extrapulmonary tuberculosis cases diagnosed by fine needle aspiration
      cytology and biopsy were included. Frequency of extrapulmonary tuberculosis in
      the lymph nodes in relation to age and sex were studied. RESULTS: Lymph nodes
      tuberculosis was present in 179 (69.11%) cases. Among all extrapulmonary
      tuberculosis, 132 (50.56%) cases were in males and 127 (49.04%) were in females.
      Out of total 179 tuberculosis of lymph nodes, 116 (74.35%) were seen in age group
      of 25 years and above (p=0.018) and 86 (48.04%) in males and 93 (51.95%) in
      females (p=0.18). CONCLUSIONS: Extrapulmonary tuberculosis is common in lymph
      nodes, equally in both sexes and more in age group of 25 and above. Therefore,
      this age group should be focused upon more for investigation and management of
      extrapulmonary tuberculosis.

PMID- 21879016
TI  - Antiphospholipid syndrome in childhood systemic lupus erythematosus.
AB  - Antiphospholipid syndrome is an autoimmune disease that presents with recurrent
      arteriovenous thrombosis, repeated pregnancy loss and elevated titres of
      antiphospholipid antibodies in the blood. It is a common cause of acquired
      thrombosis and can manifest within any part of the vascular tree. Inferior
      Venacava thrombosis at outset, however, is not a common manifestation of systemic
      lupus erythematosus associated-antiphospholipid syndrome particularly in
      children. Here, we present a 14-year old girl who developed antiphospholipid
      syndrome as a presenting manifestation of systemic lupus erythematosus.

PMID- 21879017
TI  - Childhood neurological illness in Nepal.
AB  - The commonly encountered neurological disorders in Nepalese children are febrile
      encephalopathies, neurocysticercosis, and epilepsy, and neonatal encephalopathy,
      neuro-psychiatric and neuromuscular disease. Also, these children in Nepal remain
      one of the most vulnerable and marginalized groups in the community. Due to the
      lack of proper facilities some preventable and treatable neurological conditions
      continue to paralyze the children's physical and mental health. The alarmingly
      high prevalence of these neurological illnesses has high mortality and morbidity
      in children ultimately adding financial burden to the family, society and the
      country as a whole. The paucity of data and difficulties in proper collection of
      reliable facts further hampers to understand the actual magnitude of this
      problem.

PMID- 21879018
TI  - Mortality statistics from national censuses: a low cost viable method.
AB  - Information related to mortality is pivotal for evidence based policy and
      planning, resource mobilization and impact of intervention. This information is
      essential to monitor trends in health situation of the population, detect new
      epidemics, encourage research into avoidable causes of death, evaluate the
      success of control programs, and improve accountability for expenditures on
      disease control. Sixty percent of the countries of the world don't provide enough
      information on vital events and complete and representative information. Apart
      from vital registration system, other methods for getting mortality data are in
      current practices, such as facility based information system, censuses, household
      survey, research demographic surveillance sites, epidemiological studies and
      sample vital registration system, which complement the national health
      information system. All methods have their limitations. Piggy backing of national
      censuses for mortality statistics would follow the principle of Sample
      Registration System (SRS) using verbal autopsy tools to generate the mortality
      data just after the censuses. This method can be the suitable/useful mortality
      measuring system representing the population by age, sex, location and causes of
      death with less effort and at a lower cost. This method can be used to verify
      mortality data collected from other sources and/or for adjustment of existing
      mortality data.

PMID- 21879019
TI  - Formaldehyde.

PMID- 21879020
TI  - Certain glass wool fibers (inhalable).

PMID- 21879029
TI  - One-PCR-tube approach for in situ DNA isolation and detection.
AB  - Traditional real-time polymerase chain reaction (PCR) requires a purified DNA
      sample for PCR amplification and detection. This requires PCR tests be conducted
      in clean laboratories, and limits its applications for field tests. This work
      developed a method that can carry out DNA purification, amplification and
      detection in a single PCR tube. The polypropylene PCR tube was first treated with
      chromic acid and peptide nucleic acids (PNA) as DNA-capturer were immobilized on
      the internal surface of the tube. Cauliflower mosaic virus 35S (CaMV-35S)
      promoter in the crude extract was hybridized with the PNA on the tube surface,
      and the inhibitors, interfering agents and irrelevant DNA in the crude extract
      were effectively removed by rinsing with buffer solutions. The tube that has
      captured the target DNA can be used for the following real-time PCR (RT-PCR). By
      using this approach, the detection of less than 2500 copies of 35S plasmids in a
      complex sample could be completed within 3 hours. Chocolate samples were tested
      for real sample analysis, and 35S plasmids in genetically modified chocolate
      samples have been successfully identified with this method in situ. The novel One
      PCR-tube method is competitive for commercial kits with the same time and simpler
      operation procedure. This method may be widely used for identifying food that
      contains modified DNA and specific pathogens in the field.

PMID- 21879030
TI  - Nanoparticle microinjection and Raman spectroscopy as tools for nanotoxicology
      studies.
AB  - Microinjection techniques and Raman spectroscopy have been combined to provide a
      new methodology to investigate the cytotoxic effects due to the interaction of
      nanomaterials with cells. In the present work, this novel technique has been used
      to investigate the effects of Ag and Fe(3)O(4) nanoparticles on Hela cells. The
      nanoparticles are microinjected inside the cells and these latter ones are probed
      by means of Raman spectroscopy after a short incubation time, in order to
      highlight the first and impulsive mechanisms developed by the cells to counteract
      the presence of the nanoparticles. The results put in evidence a different
      behaviour of the cells treated with nanoparticles in comparison with the control
      cells; these differences are supposed to be generated by an emerging oxidative
      stress due to the nanoparticles. The achieved results demonstrate the suitability
      of the proposed method as a new tool for nanotoxicity studies.

PMID- 21879031
TI  - Preparation of cation-exchange stir bar sorptive extraction based on monolithic
      material and its application to the analysis of soluble cations in milk by ion
      chromatography.
AB  - In this study, a new cation-exchange coating for stir bar sorptive extraction
      (SBSE) based on poly (acrylic acid-ethylene dimethacrylate) monolithic material
      was synthesized. The effect of polymerization conditions such as the ratio of
      functional monomer to cross-linker and the content of porogenic solvent on the
      extraction efficiencies were investigated in detail. The monolithic material was
      characterized by elemental analysis, scanning electron microscopy and infrared
      spectroscopy. In order to evaluate the usability of the new coating for the
      extraction of inorganic cations, the analysis of soluble K(+), Mg(2+) and Ca(2+)
      in milk by ion chromatography with conductivity detection was selected as a
      paradigm. Several extractive parameters, including pH value in sample matrix,
      desorption solvent, extraction and desorption time were optimized. Under the
      optimum conditions, low detection limits (S/N = 3) and quantification limits (S/N
      = 10) of the proposed method for the target cations were achieved within the
      range of 0.12-0.28 and 0.4-0.92 MUg L(-1), respectively. The method also showed
      good linearity, simplicity, practicality and low cost for the extraction of
      inorganic cations. Finally, the proposed method was successfully used to analyse
      three different trademarks of commercial milk samples with satisfactory
      recoveries in the range of 71.1% to 102.8%.

PMID- 21879032
TI  - Determination of morphine at gold nanoparticles/Nafion(r) carbon paste modified
      sensor electrode.
AB  - A novel and effective electrochemical sensor for the determination of morphine
      (MO) in 0.04 mol L(-1) universal buffer solution (pH 7.4) is introduced using
      gold nanoparticles electrodeposited on a Nafion modified carbon paste electrode.
      The effect of various experimental parameters including pH, scan rate and
      accumulation time on the voltammetric response of MO was investigated. At the
      optimum conditions, the concentration of MO was determined using differential
      pulse voltammetry (DPV) in a linear range of 2.0 * 10(-7) to 2.6 * 10(-4) mol L(
      1) with a correlation coefficient of 0.999, and a detection limit of 13.3 * 10(
      10) mol L(-1), respectively. The effect of common interferences on the current
      response of morphine namely ascorbic acid (AA) and uric acid (UA) is studied. The
      modified electrode can be used for the determination of MO spiked into urine
      samples, and excellent recovery results were obtained.

PMID- 21879033
TI  - Oligonucleotide-based label-free Hg2+ assay with a monomer-excimer fluorescence
      switch.
AB  - A novel fluorescent Hg(2+) sensor was developed based on the T-Hg(2+)-T structure
      and a thioflavine T monomer-excimer fluorescent switch. Under optimum conditions,
      the selectivity is remarkably high, and Hg(2+) can be quantified over the dynamic
      range of 0.1 to 1.2 MUM, with a limit of detection (LOD) of ~20 nM and a linear
      correlation coefficient of 0.995.

PMID- 21879034
TI  - Conjugation of quantum dots with graphene for fluorescence imaging of live cells.
AB  - It is difficult to achieve fluorescent graphene-quantum dots (QDs) conjugation
      because graphene quenches the fluorescence of the QDs. In the present study, the
      conjugation of graphene (reduced graphene oxide, RGO) with QDs via a bridge of
      bovine serum albumin (BSA) provides a novel highly fluorescent nano probe for the
      first time. BSA capped QDs are firmly grafted onto polyethylenimine
      (PEI)/poly(sodium 4-styrenesulfonate) (PSS) coated RGO (graphene-QDs) via
      electrostatic layer by layer assembly. The strong luminescence of the graphene
      QDs provides a potential for non-invasive optical in vitro imaging. The graphene
      QDs are used for in vitro imaging of live human carcinoma (Hela) cells. Graphene
      QDs could be readily up-taken by Hela cells in the absence of specific targeting
      molecules, e.g., antibodies or folic acid, and no in vitro cytotoxicity is
      observed at 360 MUg mL(-1) of the graphene-QDs. The results for the imaging of
      live cells indicated that the cell-penetrating graphene-QDs could be a promising
      nano probe for intracellular imaging and therapeutic applications.

PMID- 21879035
TI  - Direct determination of free metal concentration by implementing stripping
      chronopotentiometry as the second stage of AGNES.
AB  - The electroanalytical technique Absence of Gradients and Nernstian Equilibrium
      Stripping (AGNES) has been extended by applying stripping chronopotentiometry
      (SCP) as the re-oxidation stage in the determination of the free concentration of
      Zn(2+), Cd(2+) and Pb(2+). This new approach, called AGNES-SCP, has been
      implemented with screen-printed electrodes (SPE) and the standard Hanging Mercury
      Drop Electrode (HMDE). Clear advantages of this variant have been shown: (i) the
      easy resolution of the peaks of different metals present in mixtures and (ii) the
      sparing of blanks. A rigorous computation of the faradaic charge along the SCP
      stage takes into account the contribution of other oxidants, which can be
      efficiently measured at the end of the deposition stage of AGNES. The free Cd
      concentration determined in an oxalate solution at pH 6 with an HMDE as the
      working electrode agreed well with values obtained with a Cd Ion Selective
      Electrode. The free metal concentration measured using an SPE for the system Cd
      and nitrilotriacetic acid (NTA) at pH = 4.8 also conformed well with Visual
      MINTEQ results.

PMID- 21879036
TI  - Single particle technique for one-step homogeneous detection of cancer marker
      using gold nanoparticle probes.
AB  - In this paper, we reported a single particle technique for the one-step
      homogeneous immunoassay of a cancer marker by resonance light scattering
      correlation spectroscopy (RLSCS). The setup of RLSCS was similar to fluorescence
      correlation spectroscopy (FCS), and its principle was based on measuring the
      resonance light scattering fluctuations in a small volumes (less than 1 fL) due
      to Brownian motion of single particles. In homogeneous immunoassay, we used a
      sandwich strategy and conjugated two different antibodies (Ab) with gold
      nanoparticles (GNPs) respectively. When two different GNPs labeled with
      antibodies are mixed in a sample containing antigen (Ag) targets, the binding of
      targets will cause GNPs to form dimers (or oligomers), which leads to the
      significant increase in the characteristic diffusion time of GNPs in the
      detection volume. The RLSCS method can sensitively detect the change in the
      characteristic diffusion time of GNPs before and after immune reactions. We used
      this technology in homogeneous immunoassays for the liver cancer biomarker alpha
      fetoprotein (AFP). The conditions of the immune reaction were investigated
      systematically. In the optimal conditions, the linear range of this assay is from
      1 pM to 1 nM and the detection limit is 1 pM for AFP. This new method was
      successfully applied for the direct determination of AFP levels in sera from
      healthy subjects and cancer patients. Our results were in good agreement with
      ELISA assays.

PMID- 21879037
TI  - Two-dimensional difference gel electrophoresis applied for analytical proteomics:
      fundamentals and applications to the study of plant proteomics.
AB  - The present review reports the principles, fundamentals and some applications of
      two-dimensional difference gel electrophoresis for analytical proteomics based on
      plant proteome analysis, also emphasizing some advantages of 2-D DIGE over 2-D
      PAGE techniques. Some fluorescent protein labeling reagents, methods of protein
      labeling, models of 2-D DIGE experiments, and some limitations of this technique
      are presented and discussed in terms of 2-D DIGE plant proteomes. Finally, some
      practical applications of this technique are pointed out, emphasizing its
      potentialities in plant proteomics.

PMID- 21879038
TI  - On-chip sample pretreatment using a porous polymer monolithic column for solid
      phase microextraction and chemiluminescence determination of catechins in green
      tea.
AB  - A porous polymer monolithic column for solid-phase microextraction and
      chemiluminescence detection was integrated into a simple microfluidic chip for
      the extraction and determination of catechins in green tea. The porous polymer
      was prepared by poly(glycidyl methacrylate-co-ethylene dimethacrylate) and
      modified with ethylenediamine. Catechins can be concentrated in the porous
      polymer monolithic column and react with potassium permanganate to give
      chemiluminescence. The microfluidic chip is reusable with high sensitivity and
      very low reagent consumption. The on-line preconcentration and detection can be
      realized without an elution step. The enrichment factor was calculated to be
      about 20 for catechins. The relative chemiluminescence intensity increased
      linearly with concentration of catechin from 5.0 * 10(-9) to 1.0 * 10(-6) M and
      the limit of detection was 1.0 * 10(-9) M. The proposed method was applied to
      determine catechin in green tea. The recoveries are from 90% to 110% which
      benefits the actual application for green tea samples.

PMID- 21879039
TI  - Sequential chemical deposition of metal alloy jellyfish using polyaniline: redox
      chemistry at the metal-polymer interface.
AB  - We here demonstrate for the first time the fabrication of jellyfish-like Au-Ag
      alloys through sequential chemical deposition on a PANI substrate. This
      methodology can be applied to fabricate not only nanoparticles with complex
      morphology but also alloys with various compositions.

PMID- 21879041
TI  - Monodisperse upconversion Er3+/Yb3+:MFCl (M = Ca, Sr, Ba) nanocrystals
      synthesized via a seed-based chlorination route.
AB  - Monodisperse Yb(3+)/Er(3+):MFCl nanocrystals were fabricated via a simple and
      effective seed-based chlorination route for the first time. Remarkably, their
      upconversion emissions are found to be greatly intensified compared with those of
      the well-reported Er(3+)/Yb(3+):SrF(2) with the same size and shape.

PMID- 21879040
TI  - TBAI-catalyzed oxidative coupling of aminopyridines with beta-keto esters and 1,3
      diones-synthesis of imidazo[1,2-a]pyridines.
AB  - TBAI could catalyze the direct oxidative C-N coupling of 2-aminopyridines with
      beta-keto esters and 1,3-diones, which affords imidazo[1,2-a]pyridines as the
      products. The reaction was realized under metal-free conditions by using tert
      butyl hydroperoxide (TBHP) as the oxidant.

PMID- 21879042
TI  - A new ligand and its complex with multi-stimuli-responsive and aggregation
      induced emission effects.
AB  - A new ligand containing tetraphenylethylene and terpyridine moieties, and its
      zinc ion complex were synthesized. Both of them exhibit an aggregation-induced
      emission effect. Their colors and emissions can be smartly switched by various
      external stimuli including grinding, heating and solvent-fuming, as well as
      exposure to acid and base vapors.

PMID- 21879043
TI  - Glycosphingolipid synthesis employing a combination of recombinant
      glycosyltransferases and an endoglycoceramidase glycosynthase.
AB  - Glycosynthase mutants of Rhodococcus sp. endo-glycoceramidase II efficiently
      synthesize complex glycosphingolipids. Glycosyl fluoride donors may be assembled
      via sequential glycosyltransferase-catalysed glycosylation of lactosyl fluoride.
      Alternatively, lactosyl fluoride may be coupled to sphingosine prior to
      subsequent glycosylation steps.

PMID- 21879044
TI  - Properties of ionic liquids on Au surfaces: non-conventional anion exchange
      reactions with carbonate.
AB  - A simple anion metathesis in diluted aqueous carbonate at room temperature
      affords 1-(12-mercaptododecyl)-3-methyl-imidazolium carbonate (MDMI-HCO(3)) from
      MDMI salts self-assembled on gold films and nanoparticles. The properties of MDMI
      SAM differ from MDMI in solution, for which the anion exchange reaction does not
      proceed.

PMID- 21879045
TI  - An energy efficient and facile synthesis of high molecular weight polyesters
      using ketenes.
AB  - A facile, ketene-based strategy for the synthesis of polyesters from stable
      Meldrum's acid monomers has been developed which overcomes many issues associated
      with traditional step-growth procedures. A significant increase in polymerization
      efficiency is observed with only 10 min reaction time at 220  degrees C being
      needed to obtain high molecular weight polymers.

PMID- 21879046
TI  - Pore partition effect on gas sorption properties of an anionic metal-organic
      framework with exposed Cu2+ coordination sites.
AB  - Presented here is an anionic nanoporous framework material with mobile guest
      cations which can perform ion exchanges with different tetraalkylammonium
      cations, and the resulting tunable pore structures exhibit interesting pore
      partition effects on gas storage and separation.

PMID- 21879047
TI  - A Zn2GeO4-ethylenediamine hybrid nanoribbon membrane as a recyclable adsorbent
      for the highly efficient removal of heavy metals from contaminated water.
AB  - Zn(2)GeO(4)-ethylenediamine (ZGO-EDA) hybrid nanoribbons have been synthesized on
      a large-scale and directly assembled to membranes, which exhibit an excellent
      recyclability, high selectivity, and good thermal stability for highly efficient
      removal of heavy metal ions, i.e., Pb(2+), Cd(2+), Co(2+), and Cu(2+), from
      contaminated water.

PMID- 21879049
TI  - Selective reductive transformations using samarium diiodide-water.
AB  - Samarium diiodide (SmI(2)) is one of the most important reductive electron
      transfer reagents available in the laboratory. Key to the popularity of SmI(2) is
      the ability of additives and co-solvents to tune the properties of the reagent.
      Over the last decade water has emerged as a particularly valuable additive,
      opening up new chemical space and leading to the discovery of unprecedented
      selectivity and new reactions promoted by SmI(2). In this Feature Article we
      review recent progress in the application of SmI(2)-H(2)O systems, with an
      emphasis on mechanistic considerations and the development of new
      transformations.

PMID- 21879048
TI  - Mesoionic thiazol-5-ylidenes as ligands for transition metal complexes.
AB  - The first examples of thiazol-5-ylidene complexes featuring group 9, 10 and 11
      metal centers, have been prepared by deprotonation of a series of 2,3,4-triaryl
      susbtituted thiazolium salts in the presence of the corresponding transition
      metal precursor.

PMID- 21879050
TI  - Enhancing the luminescence of carbon dots with a reduction pathway.
AB  - Blue luminescent reduced state carbon dots were prepared by reducing carbon dots
      with NaBH(4). The quantum yield of the reduced state carbon dots increased from
      2% to 24% and the maximum emission wavelength shifted from 520 to 450 nm. This
      offers a simple pathway to enhance the luminescence of carbon dots.

PMID- 21879051
TI  - Effect of the aliphatic chain length on electrical double layer formation at the
      liquid/vacuum interface in the [C(n)mim][BF4] ionic liquid series.
AB  - Neutral impact collision ion scattering spectroscopy (NICISS) was used to
      determine the surface structure of three ionic liquids, 1-hexyl-3
      methylimidazolium [C(6)mim], 1-octyl-3-methylimidazolium [C(8)mim], 1-decyl-3
      methylimidazolium [C(10)mim] tetrafluoroborates [BF(4)]. Concentration depth
      profiles of the elements in an ionic liquid (IL) homologous series with a common
      anion were obtained. We show that separation between the oppositely charged ions
      is seen for all three ionic liquids, resulting in an electrical double layer
      formation. The surface charge shifts from more positive to more negative with
      increasing aliphatic chain length.

PMID- 21879052
TI  - Spectral and intramolecular charge transfer properties in terminal donor/acceptor
      substituted all-trans-alpha,omega-diphenylpolyenes and alpha,omega
      diphenylpolyynes.
AB  - The absorption spectra and intramolecular charge transfer (CT) properties of
      terminal donor/acceptor-substituted all-trans-alpha,omega-diphenylpolyenes (DPE)
      and alpha,omega-diphenylpolyynes (DPY) molecules with different conjugated bridge
      length and substitution modes were investigated by using quantum chemical
      calculations. We calculated the ground state structures and energy of two series
      of terminal donor/acceptor DPE and DPY by DFT method. The dependence of
      conjugation length and substitution modes of the electronic absorption spectra
      was obtained by TDDFT calculation. The hybrid-GGA XC-functional PBE0 employed in
      this work was selected from several functionals by comparing the calculated
      electronic spectral data with experimental value. The CIS-based generalized
      Mulliken-Hush (GMH) approach was further used to calculate coupling values H(AD)
      of the CT process. The calculation shows that both the HOMO-LUMO energy gaps and
      average bond length alternations between unsaturated multiple (C=C and C=C) and
      saturated single bonds (C-C) decrease regularly with the extension of
      conjugation. The effective conjugated length (ECL) of DPE and DPY with the same
      order MM > MP/PM > PP is found together with the regular red shift of the
      electronic absorption spectra with the extension of conjugation, resulting from
      the different pi-electron delocalization and conjugation efficiency. The GMH
      analysis further suggests that the CT process in both DPE and DPY is predominated
      by the through-bond mechanism. The remarkable difference of the conjugated length
      dependence of squared CT coupling between substituted DPE and DPY is the result
      of the energetic matching degree of the frontier molecular orbitals between
      donor/acceptor and the conjugated bridge.

PMID- 21879053
TI  - Side chain flexibility and protonation states of sulfur atom containing amino
      acids.
AB  - We present a set of new data allowing elucidation of the energetic,
      conformational and vibrational features of cysteine (Cys) and methionine (Met),
      i.e. two natural amino acids (AAs) containing a sulfur atom in their side chains.
      Special attention has been paid to cysteine, for which vibrational features were
      analysed in a wide pH range (6-to-12), where its backbone can switch from a
      zwitterionic to an anionic form, and its side chain SH group can be deprotonated.
      Through a detailed discussion on the relative acidity of the three protonation
      sites of this AA, as well as on the vibrational markers arising from zwitterionic
      and anionic backbones, we could assign the spectra recorded at pH 6, 9.2 and 12
      to three species, referred to as Cys(0), Cys(1-)(a) and Cys(2-), where the
      superscripts designate their global net charges. To bring clarification to the
      structural and vibrational features, quantum mechanical calculations based on the
      Density Functional Theory (DFT) were carried out, allowing (i) a quasi exhaustive
      energetic and side chain conformational analysis through 804 clusters of
      explicitly hydrated AAs; (ii) simulation of the observed aqueous solution
      vibrational spectra of Cys(0), Cys(-2) and Met by means of the theoretical data
      obtained from their conformationally distinct lowest energy clusters.

PMID- 21879054
TI  - The role of electron localization in the atomic structure of transition-metal 13
      atom clusters: the example of Co13, Rh13, and Hf13.
AB  - The crystalline structure of transition-metals (TM) has been widely known for
      several decades, however, our knowledge on the atomic structure of TM clusters is
      still far from satisfactory, which compromises an atomistic understanding of the
      reactivity of TM clusters. For example, almost all density functional theory
      (DFT) calculations for TM clusters have been based on local (local density
      approximation--LDA) and semilocal (generalized gradient approximation--GGA)
      exchange-correlation functionals, however, it is well known that plain DFT fails
      to correct the self-interaction error, which affects the properties of several
      systems. To improve our basic understanding of the atomic and electronic
      properties of TM clusters, we report a DFT study within two nonlocal functionals,
      namely, the hybrid HSE (Heyd, Scuseria, and Ernzerhof) and GGA+U functionals, of
      the structural and electronic properties of the Co(13), Rh(13), and Hf(13)
      clusters. For Co(13) and Rh(13), we found that improved exchange-correlation
      functionals decrease the stability of open structures such as the hexagonal
      bilayer (HBL) and double simple-cubic (DSC) compared with the compact icosahedron
      (ICO) structure, however, DFT-GGA, DFT-GGA+U, and DFT-HSE yield very similar
      results for Hf(13). Thus, our results suggest that the DSC structure obtained by
      several plain DFT calculations for Rh(13) can be improved by the use of improved
      functionals. Using the sd hybridization analysis, we found that a strong
      hybridization favors compact structures, and hence, a correct description of the
      sd hybridization is crucial for the relative energy stability. For example, the
      sd hybridization decreases for HBL and DSC and increases for ICO in the case of
      Co(13) and Rh(13), while for Hf(13), the sd hybridization decreases for all
      configurations, and hence, it does not affect the relative stability among open
      and compact configurations.

PMID- 21879055
TI  - Edge reconstruction effect in pristine and H-passivated zigzag silicon carbide
      nanoribbons.
AB  - The edge reconstruction effect of the zigzag silicon carbide nanoribbons (zz SiC
      NRs) to a stable line of alternatively fused seven and five membered rings
      without and with H passivation have been studied using first principles density
      functional theory (DFT). The both side's edges of the pristine SiC are
      respectively terminated by Si and C atoms and are called the Si-edge and the C
      edge, respectively. In the un-passivated systems, the C-edge reconstructed (Crc)
      could effectively lower the edge energy of the system, while the Si-edge
      reconstructed (Sirc) could raise the edge energy of the system. Thus, the Crc
      edge is the best edge for the edge reconstruction of the system, while the both
      edge reconstructed (brc) system is the metastability. Moreover, the brc system
      has a nonmagnetic metallic state, whereas the Crc system, as well as Sirc system,
      has a ferromagnetic metallic state. The edge reconstructed destroys the magnetic
      moment of the corresponding edge atoms. The magnetic moment arises from the
      unreconstructed zigzag edges. The pristine zz edge system has a ferrimagnetic
      metallic state. However, in the H-passivated systems, the unreconstructed zigzag
      edge (zz-H) is the best edge. The Crc-H system is the metastability. The Sirc-H
      system has only slightly higher energy than the Crc-H system, whereas the brc-H
      system of the pristine SiC NR has the highest edge energy. Thus, the H
      passivation would prevent the occurrence of edge reconstruction. Moreover, H
      passivation induces a metal-semiconductor transition in the zz and brc SiC NRs.
      Additionally, except for brc-H system which has non-magnetic semiconducting
      state, the zz-H, Crc-H, and Sirc-H systems have the magnetic state.

PMID- 21879056
TI  - Inelastic collisions of ultracold polar LiCs molecules with caesium atoms in an
      optical dipole trap.
AB  - We investigate collisions of ultracold polar LiCs molecules and ultracold caesium
      atoms. LiCs molecules are formed in an optical dipole trap by photoassociation of
      caesium and lithium atoms via the B(1)Pi excited state followed by spontaneous
      emission to the X(1)Sigma(+) ground state and the lowest triplet state
      a(3)Sigma(+). The molecules are then stored together with caesium atoms in the
      same optical trap. Rate coefficients for the loss of molecules induced by
      collisions with surrounding Cs atoms are measured for molecular ensembles
      produced via different photoassociation resonances. The results are analyzed in
      terms of the unitarity limit for the inelastic rates and predictions from the
      universal model of Idziaszek and Julienne (Phys. Rev. Lett., 2010, 104, 113202).

PMID- 21879057
TI  - Pressure enhancement in carbon nanopores: a major confinement effect.
AB  - Phenomena that occur only at high pressures in bulk phases are often observed in
      nanopores, suggesting that the pressure in such confined phases is large. We
      report a molecular simulation study of the pressure tensor of an argon nanophase
      within slit-shaped carbon pores and show that the tangential pressure is positive
      and large, while the normal pressure can be positive or negative depending on
      pore width. We also show that small changes in the bulk pressure have a large
      effect on the tangential pressure, suggesting that it should be possible to
      control the latter over wide ranges in laboratory experiments.

PMID- 21879058
TI  - Mechanism of freezing of water in contact with mesoporous silicas MCM-41, SBA-15
      and SBA-16: role of boundary water of pore outlets in freezing.
AB  - The freezing mechanism of water contacted with mesoporous silicas with uniform
      pore shapes, both cylindrical and cagelike, was studied by thermodynamic and
      structural analyses with differential scanning calorimetry (DSC) and X-ray
      diffraction (XRD) together with adsorption measurements. In the DSC data extra
      exothermic peaks were found at around 230 K for water confined in SBA-15, in
      addition to that due to the freezing of pore water. These peaks are most likely
      to be ascribed to the freezing of water present over the micropore and/or
      mesopore outlets of coronas in SBA-15. Freezing of water confined in SBA-16 was
      systematically analysed by DSC with changing the pore size. The freezing
      temperature was found to be around 232 K, close to the homogeneous nucleation
      temperature of bulk water, independent of the pore size when the pore diameter
      (d) < 7.0 nm. Water confined in the cagelike pores of SBA-16 is probably
      surrounded by a water layer (boundary water) at the outlets of channels to
      interconnect the pores and of fine corona-like pores, which is similar to that
      present at the outlet of cylindrical pores in MCM-41 and of cylindrical channels
      in SBA-15. The presence of the boundary water would be a key for water in SBA-16
      to freeze at the homogeneous nucleation temperature. This phenomenon is similar
      to those well known for water droplets in oil and water droplets of clouds in the
      sky. The XRD data showed that the cubic ice I(c) was formed in SBA-16 as
      previously found in SBA-15 when d < 8.0 nm.

PMID- 21879059
TI  - The effect of reagent charge state on the charge inversion efficiency of singly
      charged polyatomic ions in the gas phase.
AB  - A variety of combinations of oppositely charged ions have been reacted to examine
      the role of the charge state from a multiply protonated or multiply deprotonated
      reagent ion on the efficiency of conversion of a singly charged ion of opposite
      polarity to a singly charged ion of the same polarity as the reagent. Maximum
      efficiencies on the order of tens of percent were observed. A threshold for
      charge inversion was noted in all cases and, with one exception, a clear decrease
      in efficiency was also noted at high charge states. A model was developed to
      predict charge inversion efficiency based on charge states, cross-sections of the
      reactants, and relevant thermodynamic ion affinity values for the reactants and
      products. The model predicts a threshold for charge inversion, although the
      prediction does not match the observed threshold quantitatively. This discrepancy
      is likely due to a simplifying assumption that is not justified on a quantitative
      basis but which does reproduce the qualitative trend. The model does not predict
      the major decrease in efficiency at high charge states. However, calculations
      show that the kinetic energies of the charge inversion products can lead to
      significant scattering losses at high charge states of the ion-ion collision
      complex.

PMID- 21879060
TI  - A novel ruthenium(II) complex for two-photon absorption-based optical power
      limiting in the near-IR range.
AB  - In this article, the synthesis of a novel high-conjugated ligand and its
      corresponding Ru(II) complex PTFTF:Ru is reported, along with the linear and
      nonlinear optical characterizations. Two-photon absorption based optical power
      limiting properties (OPL), especially in the near infrared, are described and
      compared to those of the analogous complexes previously published. Combined with
      a preliminary theoretical approach, this allows us to highlight several key
      parameters for OPL optimization in such molecular systems and more particularly
      the spectral overlap between TPA and excited-state absorption.

PMID- 21879061
TI  - Pyrene-based organic dyes with thiophene containing pi-linkers for dye-sensitized
      solar cells: optical, electrochemical and theoretical investigations.
AB  - A new series of metal-free organic dyes containing pyrene and alpha-cyanoacrylic
      acid end groups and thiophene, bithiophene, thienylbenzene or thienylfluorene pi
      linkers were synthesized and characterized by absorption, emission and
      electrochemical measurements. Time-dependent density functional theoretical
      calculations were also performed to unravel the nature of the absorption induced
      electronic excitations. Extension of conjugation in the pi-linker by the
      incorporation of phenyl or fluorene was found to enhance the molar extinction
      coefficient while the use of thiophene red-shifted the absorption. The longer
      wavelength absorption peaks found for the dyes were attributed to pi-pi*
      transition with a contribution from the charge transfer transition which becomes
      prominent for the bithiophene bridged derivative. The bithiophene containing dye
      showed moderate overall light-to-electron conversion efficiency attributable to
      the favorable absorption and redox properties originating due to the presence of
      a bithiophene segment. The trends observed for the various dyes in the device
      performance were rationalized by electron-impedance spectroscopy measurements.

PMID- 21879062
TI  - Ionic liquid induced spontaneous symmetry breaking: emergence of predominant
      handedness during the self-assembly of tetrakis(4-sulfonatophenyl)porphyrin
      (TPPS) with achiral ionic liquid.
AB  - The self-assembly and supramolecular chirality of a dianionic tetrakis(4
      sulfonatophenyl) porphyrin (TPPS) in the presence of ionic liquids, 1-alkyl-3
      methylimidazolium tetrafluoroborate (alkyl = C(2), C(4) or C(6), abbreviated as
      C(2)mimBF(4), C(4)mimBF(4) and C(6)mimBF(4), respectively), have been
      investigated. It has been confirmed that mimBF(4) ionic liquids significantly
      promoted the J-aggregation of TPPS and the alkyl chain length in the imidazolium
      cation was closely related to the TPPS aggregation, the inducing ability of which
      decreased in the order of C(2), C(4) or C(6) in side chain. Interestingly, the
      formed TPPS assemblies with the ionic liquids showed supramolecular chirality
      although both TPPS and ionic liquids are achiral. It was found that the
      supramolecular chirality of the TPPS/IL system always appeared after the
      formation of the J aggregate. The dynamic process of the emergence of the
      handedness in the initial achiral system was monitored by the time-dependent CD
      spectra. A mechanism for the transformation of the conventional J-aggregate to
      the chiral J-aggregate was proposed. The work will lead to a deeper understanding
      of the chiral symmetry breaking in the supramolecular system.

PMID- 21879063
TI  - Metallization of solid hydrogen: the challenge and possible solutions.
AB  - The search for the means to convert molecular hydrogen to a metal under static
      conditions at high pressure is reviewed with emphasis on selected recent
      developments in both experimental studies and theoretical approaches. One
      approach suggested recently makes use of mixtures of hydrogen and suitable
      impurities. In these materials hydrogen is perturbed by impurities with the goal
      of obtaining the metallization of hydrogen at moderate pressures. This approach
      has also been extensively examined through the use of first-principles methods
      and we review this recently explored experimental approach and several
      theoretical studies that have provided an atomic-scale picture of the interaction
      of hydrogen with impurities under pressure. The objective of this novel approach
      is to help determine if metallization of hydrogen at pressures is attainable with
      currently available experimental techniques.

PMID- 21879064
TI  - Crystal growth simulations of methane hydrates in the presence of silica
      surfaces.
AB  - We present a molecular dynamics simulation study of the crystal growth of methane
      hydrates in the presence of model silica (SiO(2)) surfaces. The crystal growth
      under apparent steady-state conditions shows a clear preference for bulk
      solution. We observe rather disordered water arrangements very close to the
      silica surface within about 5 A in both liquid and crystalline regions of the
      system. These disordered structures have dynamic and structural properties
      intermediate between those exhibited by molecules in bulk liquid and crystalline
      phases. The presence of methane molecules appears to help stabilize these
      structures. We observe that under appropriate conditions, the hydroxylated silica
      surfaces can serve as a source of methane molecules which can help promote
      hydrate growth near the surfaces.

PMID- 21879065
TI  - Formation of Al2H7- anions--indirect evidence of volatile AlH3 on sodium alanate
      using solid-state NMR spectroscopy.
AB  - After more than a decade of intense research on NaAlH(4) doped with transition
      metals as hydrogen storage material, the actual mechanism of the decomposition
      and rehydrogenation reaction is still unclear. Early on, monomeric AlH(3) was
      named as a possible transport shuttle for aluminium, but never observed
      experimentally. Here we report for the first time the trapping of volatile AlH(3)
      produced during the decomposition of undoped NaAlH(4) by an adduct of sodium
      alanate and crown ether. The resulting Al(2)H(7)(-) anion was identified by solid
      state (27)Al NMR spectroscopy. Based on this indirect evidence of volatile alane,
      we present a simple description of the processes occurring during the reversible
      dehydrogenation of NaAlH(4).

PMID- 21879066
TI  - Chelatoaromaticity--existing: yes or no? An answer given by spatial magnetic
      properties (through space NMR shieldings--TSNMRS).
AB  - The spatial magnetic properties (through space NMR shieldings--TSNMRS) of metal
      complexes (with ligands such as acetylacetone, 3-hydroxy-pyran(4)one) and
      "metallobenzenes" have been calculated by the GIAO perturbation method and
      visualized as Iso-Chemical-Shielding Surfaces (ICSS) of various sizes and
      directions. The TSNMRS values, thus obtained, can be successfully employed to
      quantify and visualize partial aromaticity of the metallocyclic ring by
      comparison with the spatial magnetic properties of the corresponding non
      complexed ligands in comparable structural and electronic situations, and
      benzene, respectively. Because anisotropy/ring current effects in (1)H NMR
      spectra proved to be the molecular response property of TSNMRS, the results
      obtained concerning partial "chelatoaromaticity" are experimentally ensured.

PMID- 21879067
TI  - A recyclable bifunctional acid-base organocatalyst with ionic liquid character.
      The role of site separation and spatial configuration on different condensation
      reactions.
AB  - A series of bifunctional organic catalysts containing acid and basic sites with
      ionic liquid characteristics have been prepared and their catalytic activity and
      reaction coordinate for aldol and Knoevenagel condensations have been compared.
      While the only factor controlling catalyst activity for the Knoevenagel
      condensation was the distance between the acid and base sites, the spatial
      orientation of the organocatalyst is also key to achieve high activity and
      selectivity in the Claisen-Schmidt condensation. Mechanistic studies based on
      theoretical DFT calculations show that the acid-base bifunctional organocatalyst
      follows a mechanism inspired in natural aldolases for the synthesis of trans
      chalcones, being able to produce a large variety of these compounds of industrial
      interest. The combination of the acid-base pairs within the proper geometry and
      the ionic liquid nature makes this catalyst active, selective and recyclable.

PMID- 21879068
TI  - Chemical applications of neural networks: aromaticity of pyrimidine derivatives.
AB  - Neural networks are computational tools able to apprehend non-linear
      relationships between different parameters, having the capacity to order a large
      amount of input data and transform them into a graphical pattern of output data.
      We have previously reported their use for the quantification of the aromaticity
      through the Euclidean distance between neurons. In this article, we apply the
      method to a variety of pyrimidine derivatives with electron-donor and electron
      withdrawing groups as substituents, with capacity to produce push-pull compounds.
      We have calculated the aromaticity of benzene (as a reference molecule), parent
      pyrimidine and other 11 pyrimidine derivatives having amino, dimethylamino and
      tricyanovinyl substitution. The neural network has been generated using ASE,
      Lambda, NICS(zz)(1) and HOMA as aromaticity descriptors, since our previous work
      showed that the combination of these indices provided the best performance of the
      network. On studying the influence of the substituent on the aromaticity of the
      molecule, we have found that, opposite to benzene derivatives, all the
      substituents decrease the aromaticity of the ring. The interplay between
      aromaticity, planarity and push-pull properties of all the substituted
      pyrimidines has also been addressed. An interesting feature of the neural network
      to quantify aromaticity is that the importance of the reference reaction used to
      evaluate energy stabilization and magnetic susceptibility exaltation is
      minimized.

PMID- 21879069
TI  - Tracking thermally-activated transformations in a nanostructured
      metal/oxide/metal system.
AB  - We present experimental and theoretical evidence of sequential redox processes
      and structural transformations occurring by increasing temperature in a
      metal/oxide/metal system obtained via deposition of Fe atoms onto a z'
      TiO(1.25)/Pt(111) ultrathin film in UHV. The initial reduction of the z'-TiO(x)
      phase by Fe at room temperature is followed by Fe diffusion and partial
      penetration into the substrate at intermediate temperatures. This triggers the
      formation of a bi-component material in which mixed FeO/TiO(2) nanoislands
      coexist on a h-TiO(1.14) ultrathin film, notably restructured (from rectangular
      to hexagonal) and reduced (from Ti : O = 1 : 1.25 to 1 : 1.14) with respect to
      the original TiO(1.25) phase. Further heating recovers the pristine z'-TiO(x)
      phase while Fe completely dissolves into the substrate.

PMID- 21879070
TI  - Computing the inhomogeneous broadening of electronic transitions in solution: a
      first-principle quantum mechanical approach.
AB  - Starting from Marcus's relationship connecting the inhomogeneous broadening with
      the solvent reorganization energy and exploiting recent state-specific
      developments in PCM/TD-DFT calculations, we propose a procedure to estimate the
      polar broadening of optical transitions. When applied to two representative
      molecular probes, coumarin C153 and 4-aminophthalimide, in different solvents,
      our approach provides for the polar broadening values fully consistent with the
      experimental ones. Thanks to these achievements, for the first time fully ab
      initio vibrationally resolved absorption spectra in solution are computed,
      obtaining spectra for coumarin C153 in remarkable agreement with experiments.

PMID- 21879071
TI  - Direct measurements of the high temperature rate constants of the reactions NCN +
      O, NCN + NCN, and NCN + M.
AB  - The rate constant of the reaction NCN + O has been directly measured for the
      first time. According to the revised Fenimore mechanism, which is initiated by
      the NCN forming reaction CH + N(2)-> NCN + H, this reaction plays a key role for
      prompt NO(x) formation in flames. NCN radicals and O atoms have been
      quantitatively generated by the pyrolysis of NCN(3) and N(2)O, respectively. NCN
      concentration-time profiles have been monitored behind shock waves using narrow
      bandwidth laser absorption at a wavelength of lambda = 329.1302 nm. Whereas no
      pressure dependence was discernible at pressures between 709 mbar < p < 1861
      mbar, a barely significant temperature dependence corresponding to an activation
      energy of 5.8 +/- 6.0 kJ mol(-1) was found. Overall, at temperatures of 1826 K <
      T < 2783 K, the rate constant can be expressed as k(NCN + O) = 9.6 * 10(13)* exp(
      5.8 kJ mol(-1)/RT) cm(3) mol(-1) s(-1) (+/-40%). As a requirement for accurate
      high temperature rate constant measurements, a consistent NCN background
      mechanism has been derived from pyrolysis experiments of pure NCN(3)/Ar gas
      mixtures, beforehand. Presumably, the bimolecular secondary reaction NCN + NCN
      yields CN radicals hence triggering a chain reaction cycle that efficiently
      removes NCN. A temperature independent value of k(NCN + NCN) = (3.7 +/- 1.5) *
      10(12) cm(3) mol(-1) s(-1) has been determined from measurements at pressures
      ranging from 143 mbar to 1884 mbar and temperatures ranging from 966 K to 1900 K.
      At higher temperatures, the unimolecular decomposition of NCN, NCN + M -> C +
      N(2) + M, prevails. Measurements at temperatures of 2012 K < T < 3248 K and at
      total pressures of 703 mbar < p < 2204 mbar reveal a unimolecular decomposition
      close to its low pressure limit. The corresponding rate constants can be
      expressed as k(NCN + M) = 8.9 * 10(14)* exp(-260 kJ mol(-1)/RT) cm(3) mol(-1) s(
      1)(+/-20%).

PMID- 21879072
TI  - Supercapacitors based on self-assembled graphene organogel.
AB  - Self-assembled graphene organogel (SGO) with 3-dimensional (3D) macrostructure
      was prepared by solvothermal reduction of a graphene oxide (GO) dispersion in
      propylene carbonate (PC). This SGO was used as an electrode material for
      fabricating supercapacitors with a PC electrolyte. The supercapacitor can be
      operated in a wide voltage range of 0-3 V and exhibits a high specific
      capacitance of 140 F g(-1) at a discharge current density of 1 A g(-1).
      Furthermore, it can still keep a specific capacitance of 90 F g(-1) at a high
      current density of 30 A g(-1). The maximum energy density of the SGO based
      supercapacitor was tested to be 43.5 Wh kg(-1), and this value is higher than
      those of the graphene based supercapacitors with aqueous or PC electrolytes
      reported previously. Furthermore, at a high discharge current density of 30 A g(
      1), the energy and power densities of the supercapacitor were measured to be 15.4
      Wh kg(-1) and 16,300 W kg(-1), respectively. These results indicate that the
      supercapacitor has a high specific capacitance and power density, and excellent
      rate capability.

PMID- 21879073
TI  - Pd nanoparticles for C-C coupling reactions.
AB  - The catalytic formation of C-C bonds is one of the most useful transformations in
      organic synthesis. Over the last decade, the use of transition metal
      nanoparticles (NPs) in catalysis has attracted much interest and their use in C-C
      bond formation reactions constitutes one of their most important applications,
      including the Suzuki, Heck, and Sonogashira reactions. This tutorial review
      highlights recent work in this active area, considering the stabilising agents
      used to prepare the NPs, the catalytic results and the recycling possibilities.

PMID- 21879074
TI  - Cobalamin reduction by dithionite. Evidence for the formation of a six-coordinate
      cobalamin(II) complex.
AB  - Evidence for the formation of a unique, six-coordinate cobalamin(II) complex with
      the anion-radical SO(2)(-) during the reduction of aquacobalamin(III) by sodium
      dithionite, was obtained from spectrophotometric and EPR measurements. The pK(a)
      value of the weakly coordinated dimethylbenzimidazole group was found to be 4.8
      +/- 0.1 at 25  degrees C.

PMID- 21879075
TI  - A computational insight into a metal mediated pathway for the ring-opening
      polymerization (ROP) of lactides by an ionic {(NHC)2Ag}(+)X(-) (X = halide) type
      N-heterocyclic carbene (NHC) complex.
AB  - A metal mediated coordination-insertion pathway for the ring-opening
      polymerization (ROP) of L-lactide by an ionic {(NHC)(2)Ag}(+)X(-) (X = halide)
      type silver complex of N-heterocyclic carbene (NHC) has been investigated using
      the density functional theory (DFT) method. A clear insight into the lactide
      insertion process could be obtained by modeling two consecutive monomer addition
      steps with the first one mimicking chain initiation with the second representing
      a propagation step. In particular, in each of the cycles, the reaction initiates
      with the formation of a lactide coordinated species, [1+LL] and [2+LL] that
      transforms into a metal bound cyclic lactide intermediate, I([1+LL]->2) and
      I([2+LL]->3), which subsequently ring opens to give the lactide inserted
      products, 2 and 3. The estimated overall activation barrier for the initiation
      step is 42.0 kcal mol(-1) while the same for the propagation step is 31.5 kcal
      mol(-1). Studies on higher monomer insertions showed a decrease in the relative
      product energies as anticipated for an addition polymerization pathway.

PMID- 21879076
TI  - Binucleating behaviour of a proximally-diphosphinated calix[4]arene.
AB  - The long diphosphine 5,11-diphenylphosphanyl-25,26-dipropyloxy-27,28-bis(2
      propenyloxy) calix[4]arene (cone) (5), in which the two phosphorus atoms are
      separated by a semi-rigid linking unit, was prepared in four steps starting from
      calix[4]arene. Reaction of 5 with AuCl(SEt(2)) or [RuCl(2)(p-cymene)](2) led to
      calixarenes bearing two metallated pendant arms, [5.(AuCl)(2)] and [5.{RuCl(2)(p
      cymene)}(2)], respectively. In the presence of AgBF(4) or [Ni(C(5)H(5))(1,5
      cyclooctadiene)]BF(4), diphosphine 5 displayed a marked tendency to form
      oligomeric material, but under high dilution conditions dimeric species were
      obtained selectively. The inability of 5 to form chelate complexes was further
      illustrated by its reaction with [PdCl(2)(1,5-cyclooctadiene)(2)], which led
      quantitatively to a rare complex in which a diphosphine spans across the
      dinuclear [PdCl(MU-Cl)(2)PdCl] unit.

PMID- 21879077
TI  - Coordination of uranium(VI) with functional groups of bacterial
      lipopolysaccharide studied by EXAFS and FT-IR spectroscopy.
AB  - The complexation of uranyl ions with lipopolysaccharide (LPS), the main component
      of the cell wall of Gram-negative bacteria, was investigated on a molecular level
      with U L(III)-edge extended X-ray absorption fine structure (EXAFS) and
      attenuated total reflection Fourier transform infrared (ATR-FT-IR) spectroscopy
      over a wide pH range (2.6 to 7.0). For the first time, structural determinations
      of uranyl complexes with cell wall compounds were extended from acidic up to
      neutral pH. The main functionalities responsible for uranyl binding are
      phosphoryl and carboxyl groups. At an excess of LPS, related to environmental
      conditions, the uranyl ion is mainly complexed by phosphoryl groups four-fold
      monodentately coordinated in the equatorial plane of the uranyl dioxo cation
      UO(2)(2+) showing great homologies to the uranyl mineral phase meta-autunite in
      the EXAFS spectra. At equimolar ratios of uranyl and functional groups of LPS,
      according to a slight deficit of phosphoryl groups, additional carboxyl
      coordination in a bidentate manner becomes important as it is shown by IR
      spectroscopy. From the vibrational spectra, a mixed coordination of UO(2)(2+)
      with both phosphoryl and carboxyl groups is derived. The coordination of uranyl
      ions to the LPS molecule is obviously mainly controlled by the U/LPS
      concentration ratio, and the influence of pH is only of minor significance at the
      investigated range.

PMID- 21879079
TI  - Crystalline metal (Li, Mg, Ca, Sr, Ba, Sn, Pb) complexes of the new chelating
      N,N'-dianionic [1,2-N(R)C6H4(CH2NR)](2-) ligand (R = SiMe3, CH2Bu(t)).
AB  - 2-Aminomethylaniline was converted into the N,N'-bis(pivaloyl) (1) or 
      bis(trimethylsilyl) (2) derivative, using 2 Bu(t)C(O)Cl or 2 Me(3)SiCl (= RCl),
      respectively, with 2 NEt(3), or for 2 from successively using 2 LiBu(n) and 2
      RCl. N,N'-Bis(neopentyl)-2-(aminomethyl)aniline (3) was prepared by LiAlH(4)
      reduction of 1. From 2 or 3 and 2 LiBu(n), the appropriate dilitiodiamide {2
      [{N(Li)R}C(6)H(4){CH(2)N(Li)R}(L)](2) (L absent, 4a; or L = THF, 4b) or the N,N'
      bis(neopentyl) analogue (5) of 4a was prepared. Treatment of 4a with 2 Bu(t)NC, 2
      (2,6-Me(2)C(6)H(3)NC) or 2 Bu(t)CN (= L') furnished the corresponding adduct [2
      N{Li(L')R}C(6)H(4){CH(2)N(Li)R}] (4c, 4d or 4e, respectively), whereas 4b with 2
      PhCN afforded [2-{N(Li)R}C(6)H(4){CH(2)C(Ph) = NLi(NCPh)}] (6). The dimeric
      bis(amido)stannylene [Sn{N(R)C(6)H(4)(CH(2)NR)-1,2}](2) (7) was obtained from 4a
      and [Sn(MU-Cl)NR(2)](2), while the N,N'-bis(neopentyl) analogue 8 of 7 was
      similarly derived from [Sn(MU-Cl)NR(2)](2) and 5. Reaction of two equivalents of
      the diamine 2 with Pb(NR(2))(2) yielded 9, the lead homologue of 7. Oxidative
      addition of sulfur to 7 led to the dimeric bis(diamido)tin sulfide 10. Treatment
      of 2 successively with 'MgBu(2)' in C(5)H(12) and THF gave
      [Mg{N(R)C(6)H(4)(CH(2)NR)}(THF)](2) (11a), which by displacement of its THF by an
      equivalent portion of Bu(t)CN or PhCN produced
      [Mg{N(R)C(6)H(4)(CH(2)NR)}(CNR')(n)] [R' = Bu(t), n = 1 (11b); R' = Ph, n = 2
      (11c)]. The Ca (12), Sr (13) or Ba (14) analogues of the Mg compound 11a were
      isolated from 2 and either the appropriate compound M(NR(2))(2) (M = Ca, Sr, Ba),
      or successively 2 LiBu(n) and 2 M(OTos)(2). The new compounds 1-14 were
      characterized by microanalysis (C, H, N; not for 1, 2, 3, 5), solution NMR
      spectra, nu(max) (C=N) (IR for 4c, 4d, 4e, 6, 11b, 11c), selected EI-MS peaks
      (for 1, 2, 3, 7, 8, 9, 10), and single crystal X-ray diffraction (for 4a, 4b,
      11a).

PMID- 21879078
TI  - Fabrication of doxorubicin functionalized gold nanorod probes for combined cancer
      imaging and drug delivery.
AB  - A novel strategy was utilized to develop a stable probe based on thiolated
      poly(ethylene glycol) (SH-PEG) and polyacrylic acid (PAA) functionalized gold
      nanorods (GNRs), following the attachment of an anti-cancer drug, doxorubicin
      (DOX), to obtain PAA-PEG-GNRs@DOX assemblies. Importantly, the obtained probe as
      a novel drug-delivery and fluorescent imaging agent for simultaneous imaging of
      and drug delivery to prostate cancer cells has also been demonstrated. In
      addition to designing PAA-PEG-GNRs that passively target tumor cells for cancer
      fighting drug therapy, GNRs are also regarded as hyperthermia agents for
      photokilling cancer cells, so that the tumor would be attacked on two fronts
      simultaneously.

PMID- 21879080
TI  - Solid state synthesis of homoleptic tetracyanamidoaluminates.
AB  - Tetracyanamidoaluminates of the type LiM(2)[Al(CN(2))(4)] with M = Eu and Sr were
      prepared by solid-state metathesis reactions departing from EuF(2) (or SrF(2)),
      AlF(3), and Li(2)(CN(2)) in a 2 : 1 : 4 molar ratio. The ignition temperature of
      the exothermic formation of LiSr(2)[Al(CN(2))(4)] was obtained near 420  degrees
      C. An X-ray single-crystal structure refinement performed for
      LiEu(2)[Al(CN(2))(4)] revealed the presence of the novel homoleptic
      [Al(CN(2))(4)](5-) ion in the structure. The X-ray powder diffraction pattern of
      LiSr(2)[Al(CN(2))(4)] was indexed isotypically.

PMID- 21879081
TI  - Self-assembled decanuclear Na(I)2Mn(II)4Mn(III)4 complexes: from discrete
      clusters to 1-D and 2-D structures, with the Mn(II)4Mn(III)4 unit displaying a
      large spin ground state and probable SMM behaviour.
AB  - The synthesis, magnetic characterization and X-ray crystal structures are
      reported for five new manganese compounds, [Mn(III)(teaH(2))(sal)].(1/2)H(2)O
      (1), [Na(I)(2)Mn(II)(4)Mn(III)(4)(teaH)(6)(sal)(4)(N(3))(2)(MeOH)(4)].6MeOH (2),
      [Na(I)(2)Mn(II)(4)Mn(III)(4)(teaH)(6)(sal)(4)(N(3))(2)(MeOH)(2)](n).7MeOH (3),
      [Na(I)(2)Mn(II)(4)Mn(III)(4)(teaH)(6)(sal)(4)(N(3))(2)(MeOH)(2)](n).2MeOH.Et(2)O
      (4) and [K(I)(2)Mn(II)(4)Mn(III)(4)(teaH)(6)(sal)(4)(N(3))(2)(H(2)O)(2)](n).5MeOH
      (5). Complex 1 is a mononuclear compound, formed via the reaction of
      Mn(NO(3))(2).4H(2)O, triethanolamine (teaH(3)) and salicylic acid (salH(2)) in a
      basic methanolic solution. Compound 2 is a mixed-valent hetero-metallic cluster
      made up of a Mn(8)Na(2) decanuclear core and is formed via the reaction of sodium
      azide (NaN(3)) with 1. Compounds 3-5 are isolated as 1- or 2-D coordination
      polymers, each containing the decanuclear Mn(8)M(2) (M = Na(+) or K(+)) core
      building block as the repeating unit. Compound 3 is isolated when 1 is reacted
      with NaN(3) over a very short reaction time and forms a 1-D coordination polymer.
      Each unit displays inter-cluster bridges via the O-atoms of teaH(2-) ligands
      bonding to the sodium ions of an adjacent cluster. Increasing the reaction time
      appears to drive the formation of 4 which forms 2-D polymeric sheets and is a
      packing polymorph of 3. The addition of KMnO(4) and NaN(3) to 1 resulted in
      compound 5, which also forms a 1-D coordination polymer of the decanuclear core
      unit. The 1-D chains are now linked via inter-cluster potassium and salicylate
      bridges. Solid state DC susceptibility measurements were performed on compounds 1
      5. The data for 1 are as expected for an S = 2 Mn(III) ion, with the isothermal M
      vs. H data being fitted by matrix diagonalization methods to give values of g and
      the axial (D) and rhombic (E) zero field splitting parameters of 2.02, -2.70 cm(
      1) and 0.36 cm(-1) respectively. The data for 2-5, each with an identical
      Mn(II)(4)Mn(III)(4) metallic core, indicates large spin ground states, with
      likely values of S = 16 (+/-1) for each. Solid state AC susceptibility
      measurements confirm the large spin ground state values and is also suggestive of
      SMM behaviour for 2-5 as observed via the onset of frequency dependent out-of
      phase peaks.

PMID- 21879082
TI  - Reversible thermo-responsive luminescent metallo-supramolecular triblock
      copolymers based on platinum(II) terpyridyl chromophores with unusual aggregation
      behaviour and red-near-infrared (NIR) emission upon heating.
AB  - Two platinum(II) terpyridyl-based metallo-supramolecular triblock copolymers,
      [ClPt(tpy)PEO-PPO-PEO(tpy)PtCl](OTf)(2) (1) and [(Ph-C=C)Pt(tpy)PEO-PPO
      PEO(tpy)Pt(C=C-Ph)](OTf)(2) (2), have been synthesized and characterized. The two
      complexes were found to aggregate with PtPt and/or pi-pi interactions at high
      temperature, which have not been reported so far, as revealed by UV/Vis
      absorption, emission and (1)H NMR study. This is due to the formation of
      spherical micelles driven by the PEO-PPO-PEO copolymers at temperatures above the
      critical micelle temperature, which was confirmed by TEM and DLS. The red-near
      infrared (NIR) emission of the complexes can be switched on and off by at least
      ten cycles of heating and cooling, suggesting that the micellization was highly
      reversible.

PMID- 21879083
TI  - Anion-driven conformation control and enhanced sulfate binding utilising aryl
      linked salicylaldoxime dicopper helicates.
AB  - The synthesis and spectroscopic analysis of both "metal-only" and anion
      encapsulated dicopper(II) double helicates utilising a new 1,4-aryl spacer is
      described. X-Ray crystallographic analysis of the complexes reveal that the
      aromatic spacer increases rigidity in the complex, yet the complexes are still
      able to undergo a dramatic "coiling up" to bind anions. Spectroscopic analysis
      has shown a clear enhancement in the binding strength of SO(4)(2-) over the non
      coordinating anions ClO(4)(-), NO(3)(-) and Br(-) which has been attributed to a
      combination of enhanced rigidity in the complex and an increased electrostatic
      interaction between the complex and the dianion.

PMID- 21879084
TI  - Intracrystalline diffusion in metal organic framework during heterogeneous
      catalysis: influence of particle size on the activity of MIL-100 (Fe) for
      oxidation reactions.
AB  - Three MIL-100 (Fe) samples differing in average crystal size (from 60-70 to >400
      nm) have been synthesized by microwave heating using three HF/Fe(3+) ratios.
      Oxidation of diphenylmethane with tert-butylhydroperoxide (TBHP) and thiophenol
      with oxygen are catalyzed by three MIL-100 (Fe) samples with similar reaction
      rates regardless of its average particle size. In contrast, the activity of the
      three MIL-100 (Fe) samples for the oxidation of bulky triphenylmethane by TBHP
      largely depends on the average crystal size of the sample: the smaller the
      average particle size, the larger the initial reaction rate of triphenylmethane
      oxidation. These results show that diffusion limitation takes place on MOF
      catalysis depending on the substrate size and provides indirect evidence that
      these reactions take place inside the intracrystalline space of the porous
      catalysts.

PMID- 21879085
TI  - Luminescent rhenium(I) complexes with acetylamino- and trifluoroacetylamino
      containing phenanthroline ligands: anion-sensing study.
AB  - A series of rhenium complexes with acetylamino- and trifluoroacetylamino
      containing 1,10-phenanthroline ligands have been synthesized, characterized and
      their photophysical and electrochemical properties studied. These complexes were
      found to show significant UV-vis and emission changes on addition of CN(-), F(-)
      and AcO(-) anions. Their reactivity towards CN(-), F(-) and AcO(-) anions, was
      also investigated by UV-vis, emission and (1)H NMR spectroscopy. The reaction
      product between the trifluoroacetylamino-containing 1,10-phenanthroline ligand
      and the CN(-) anion has also been structurally characterized by X-ray
      crystallography.

PMID- 21879086
TI  - Calix[4]arenes with one and two N-linked imidazolium units as precursors of N
      heterocyclic carbene complexes. Coordination chemistry and use in Suzuki-Miyaura
      cross-coupling.
AB  - The calix[4]arene-imidazolium salts 5-(3-butyl-1-imidazolylium)-25,26,27,28
      tetrabenzyloxy-calix[4]arene bromide (cone) (2), and 5,11-bis(3-alkyl-1
      imidazolylium)-25,26,27,28-tetrabenzyloxycalix[4]arene diiodide (cone) (R =
      methyl, 3a; R = n-butyl, 3b) have been synthesised. Reaction of 2 in dioxane with
      PdCl(2) in the presence of CsCO(3) and KBr (80  degrees C, 24 h) gives the
      carbene complex trans-[PdBr(2)(calix-monocarbene)(2)] (14), containing two N
      heterocyclic carbene ligands derived from 2 (yield: 63%). Repeating the reaction
      in pyridine instead of dioxane gives the mixed pyridine-carbene complex trans
      [PdBr(2)(calix-carbene)(pyridine)] (15) in 75% yield. Treatment of the bis
      imidazolium salt 3a with [Pd(OAc)(2)] affords a chelate complex, trans
      [PdI(2){calix-bis(carbene)}] (16), in which a metallo-(bis-carbene) fragment caps
      the upper rim of the calixarene basket. Complex 16, as well as its analogue 17,
      obtained from 3b, display apparent C(s)-symmetry in solution. This is not the
      case in the solid state, a single X-ray diffraction study carried out for 16
      revealing a pinced cone structure for the calixarene skeleton, which reduces the
      symmetry to C(1). The chelate complex 17 shows poor activity in Suzuki-Miyaura
      cross-coupling of phenyl boronic acid and p-tolyl halides, an observation that
      suggests the presence of a strained metallocyclic unit preventing easy
      stereochemical rearrangement to an active species. Unlike 17, complexes 14 and 15
      show good activities in cross-coupling. A comparative study using the carbene
      precursor 1-butyl-3-(2,6-diisopropylphenyl)imidazolium bromide (18), which is
      devoid of the receptor fragment, strongly suggests that the carbene ligands of 14
      and 15 operate typically as bulky NHC-ligands.

PMID- 21879087
TI  - Isomeric separation in donor-acceptor systems of Pd(II) and Pt(II) and a combined
      structural, electrochemical and spectroelectrochemical study.
AB  - Compounds of the form [(pap)M(Q(2-))] (pap = phenylazopyridine; Q = 3,5-di-tert
      butyl-benzoquinone, M = Pd, 1a and 1b, M = Pt, 2a and 2b; Q = 4-tert-butyl
      benzoquinone, M = Pd, 3a and 3b; M = Pt, 4a and 4b) were synthesized in a one-pot
      reaction. The geometrical isomers, which are possible because of the built in
      asymmetry of these ligands, have been separated by using different temperatures
      and variable solubility. Structural characterization of 1b shows that the metal
      centers are in a square planar environment, the pap ligand is in the unreduced
      neutral state and the quinones are in the doubly reduced, Q(2-) catecholate form.
      Cyclic voltammetric measurements on the complexes display two one-electron
      oxidations and two one-electron reductions. EPR and vis-NIR spectra of the one
      electron oxidized forms of the complexes indicate that the first oxidation takes
      place on the Q(2-) ligands to produce a metal bound semiquinone (Q(-)) radical.
      Reduction takes place on the pap ligand, generating metal bound pap(-) as seen
      from the (14)N (I = 1) coupling in their EPR spectrum. All the complexes in their
      [(pap)M(Q(2-))] neutral forms show strong absorptions in the NIR region which are
      largely LLCT (ligand to ligand charge transfer) in origin. These NIR bands can be
      tuned over a wide energy range by varying the metal center as well as the Q
      ligand. In addition, the intensity of NIR bands can be switched on and off by a
      simple electron transfer at relatively low potentials. DFT studies were used to
      corroborate these findings.

PMID- 21879089
TI  - Novel neutral hexacoordinate benzamidinatosilicon(IV) complexes with SiN3OF2,
      SiN3OCl2, SiN3OBr2, SiN5O and SiN3O3 skeletons.
AB  - The neutral pentacoordinate monoamidinatosilicon(IV) complex 1 (SiN(2)Cl(3)
      skeleton) and the neutral hexacoordinate monoamidinatosilicon(IV) complexes 2-9
      (SiN(3)OF(2), SiN(3)OCl(2), SiN(3)OBr(2), SiN(5)O and SiN(3)O(3) skeletons) were
      synthesised and characterised by elemental analyses, single-crystal X-ray
      diffraction (except for 1) and NMR spectroscopy in the solid state and in
      solution. Compounds 2-9 contain one bidentate monoanionic N,N'
      diisopropylbenzamidinato ligand, one bidentate monoanionic ligand derived from 8
      hydroxyquinoline and (i) two identical monoanionic ligands (F, Cl, Br, N(3), NCO,
      NCS, OSO(2)CF(3)) or (ii) one bidentate dianionic benzene-1,2-diolato ligand. The
      dynamic behavior of 2-4 (SiN(3)OX(2) skeleton; X = F, Cl, Br) and 9 (SiN(3)O(3))
      in solution was studied by multinuclear variable-temperature NMR experiments.
      Compound 1 was synthesised by reaction of SiCl(4) with the corresponding lithium
      amidinate, and compound 2 was obtained by reaction of 1 with 8-hydroxyquinoline
      and triethylamine. Compound 2 served as the starting material in the syntheses of
      3-9, in which the two chloro ligands of 2 were substituted by two identical
      (pseudo)halogeno ligands, two trifluoromethanesulfonato ligands or one benzene
      1,2-diolato ligand. Compounds 3 and 4 contain the novel SiN(3)OBr(2) and
      SiN(3)OF(2) skeletons, while compounds 5-7 are the first neutral hexacoordinate
      silicon(IV) complexes with an SiN(5)O skeleton.

PMID- 21879088
TI  - Synthesis, structures and anti-malaria activity of some gold(I) phosphine
      complexes containing seleno- and thiosemicarbazonato ligands.
AB  - A series of both mono- and dinuclear gold(I) phosphine complexes containing
      monoanionic seleno- and thiosemicarbazones as ligands were prepared and fully
      characterized by spectroscopic methods and, in some cases, by single crystal X
      ray diffraction. The in vitro anti-malaria activity of some of these compounds
      was investigated in chloroquine sensitive strains of Plasmodium falciparum. The
      IC(50) results show that the sulfur containing compounds exhibit activity similar
      to that of chloroquine, whilst the selenium derivatives display only moderate
      anti-malaria activity.

PMID- 21879090
TI  - Pd(II) and Ni(II) complexes featuring a "phosphasalen" ligand: synthesis and DFT
      study.
AB  - A phosphorus analog of salen ligands featuring iminophosphorane functionalities
      in place of the imine groups was synthesised in 2 steps from o
      diphenylphosphinophenol via the preparation of the corresponding bis
      aminophosphonium salt. This novel tetradentate ligand (1), which we named
      phosphasalen, was coordinated to Pd(II) and Ni(II) metal centres affording
      complexes 6 and 7 respectively, which were characterised by multinuclear NMR,
      elemental and X-ray diffraction analyses. Both neutral complexes adopt a nearly
      square-planar geometry around the metal with coordination of all iminophosphorane
      and phenolate moieties. The electronic properties of these new complexes were
      investigated by cyclic voltammetry and comparison with known salens was made when
      possible. Moreover, the particular behaviour of the phosphasalen nickel complex 7
      was further investigated through magnetic moment measurements and a DFT study.

PMID- 21879091
TI  - Synthesis and characterization of diiron dithiolate complexes containing a
      quinoxaline bridge.
AB  - A potential model complex for the hydrogenase active site, [Fe(2){(MU
      CH(2)S)(2)R}(CO)(6)] (1) (R = quinoxaline), was synthesized by condensation of
      [(MU-LiS)(2)Fe(2)(CO)(6)] with 2,3-bis(bromomethyl)quinoxaline. Reactions of 1
      with bis(diphenylphosphino)methane (dppm) under a range of conditions yielded
      substituted complexes [Fe(2){(MU-CH(2)S)(2)R}(CO)(5)(dppm)] (2), [Fe(2){(MU
      CH(2)S)(2)R}(CO)(4)(k(2)-dppm)] (3) and [Fe(2){(MU-CH(2)S)(2)R}(CO)(4)(MU-dppm)]
      (4). X-ray crystallography confirms that in 2, the dppm is terminally bonded to
      an iron atom via one phosphorus atom, whereas in 3, it acts as a chelating ligand
      to coordinate to an iron center in a dibasal-substituted manner. In 4, the dppm
      bridges the two iron atoms in a cis basal/basal fashion with one phosphorus
      bonded to each iron atom. Treatment of 1 with various tertiary phosphines at room
      temperature in acetonitrile (MeCN) generates a range of mono-substituted products
      [Fe(2){(MU-CH(2)S)(2)R}(CO)(5)L] (5, L = PEt(3); 6, PMe(3); 7, PPh(3); 8,
      Me(2)PPh). With Bu(t)NC, mono- and di-substituted [Fe(2){(MU
      CH(2)S)(2)R}(CO)(5)(Bu(t)NC)] (9) and [Fe(2){(MU-CH(2)S)(2)R}(CO)(4)(Bu(t)NC)(2)]
      (10) complexes are generated. All the complexes were characterized by elemental
      analysis, IR, MS and NMR spectroscopy. IR and NMR spectroscopic studies suggest
      that addition of excess HBF(4).OEt(2) acid to 1-4 led to the protonation of
      quinoxaline nitrogen atoms. In contrast, 5-10 were not stable in acidic media.
      Electrochemistry of 1-4 was investigated in the acetonitrile medium (0.1 M
      Bu(4)NPF(6)). The electrochemical instability of the reduced ligand, quinoxaline,
      and the reduced forms of these complexes revealed from the electrochemical
      studies suggests that they do not provide ideal models of the hydrogenase active
      site.

PMID- 21879092
TI  - Rattle-type hollow CaWO4:Tb(3+)@SiO2 nanocapsules as carriers for drug delivery.
AB  - Rattle-type hollow nanocapsules are among of the most promising candidates as
      drug carriers owing to their huge inner space and multifunctional material
      combination. In this paper, rattle-type hollow CaWO(4):Tb(3+)@SiO(2) nanocapsules
      with a diameter of 100-110 nm and a wall thickness around 10 nm were fabricated.
      The hollow silica nanospheres were used as nano-reactors and the luminescent core
      of CaWO(4):Tb(3+) was post-filled into the nano-reactors by a vacuum nano-casting
      route combined with a Pechini-type sol-gel method. Subsequently, doxorubicin
      hydrochloride (DOX), a model of an anti-cancer drug, is loaded into the
      CaWO(4):Tb(3+)@SiO(2) nanocapsules and their cell cytotoxicity, cancer cell
      uptake and drug release behavior are investigated in vitro. The prepared
      multifunctional inorganic nanocapsules show a loading capacity for DOX as high as
      124 mg g(-1) and sustained-release properties. The release profile of the drug
      from DOX-loaded nanocapsules can last over five days. Besides, the blank
      CaWO(4):Tb(3+)@SiO(2) shows very low cytotoxicity against cancer cell lines (HeLa
      cell) while the DOX-loaded nanocapsules exhibit relatively high efficiency for
      killing of HeLa cells. The rapid cancer cell uptake process is observed by
      confocal laser scanning microscopy. The results indicate that a rattle-type
      hollow CaWO(4):Tb(3+)@SiO(2) nanocapsule has the potential to be used as drug
      carrier in therapy. Moreover, it is possible to extend the synthetic strategy in
      this study to other rattle-type multifunctional composites to meet various
      demands.

PMID- 21879093
TI  - Smooth C(alkyl)-H bond activation in rhodium complexes comprising abnormal
      carbene ligands.
AB  - Rhodation of trimethylene-bridged diimidazolium salts induces the intramolecular
      activation of an alkane-type C-H bond and yields mono- and dimetallic complexes
      containing a formally monoanionic C,C,C-tridentate dicarbene ligand bound to each
      rhodium centre. Mechanistic investigation of the C(alkyl)-H bond activation
      revealed a significant rate enhancement when the carbene ligands are bound to the
      rhodium centre via C4 (instantaneous activation) as compared to C2-bound carbene
      homologues (activation incomplete after 2 days). The slow C-H activation in
      normal C2-bound carbene complexes allowed intermediates to be isolated and
      suggests a critical role of acetate in mediating the bond activation process.
      Computational modelling supported by spectroscopic analyses indicate that halide
      dissociation as well as formation of the agostic intermediate is substantially
      favoured with C4-bound carbenes. It is these processes that discriminate the C4-
      and C2-bound systems rather than the subsequent C-H bond activation, where the
      computed barriers are very similar in each case. The tridentate dicarbene ligand
      undergoes selective H/D exchange at the C5 position of the C4-bound carbene
      exclusively. A mechanism has been proposed for this process, which is based on
      the electronic separation of the abnormal carbene ligand into a cationic N-C-N
      amidinium unit and a metalla-allyl type M-C-C fragment.

PMID- 21879094
TI  - Syntheses, crystal structures, reactivity, and photochemistry of gold(III)
      bromides bearing N-heterocyclic carbenes.
AB  - Gold(I) complexes bearing N-heterocyclic carbenes (NHC) of the type (NHC)AuBr
      (3a/3b) [NHC = 1-methyl-3-benzylimidazol-2-ylidene (= MeBnIm), and 1,3
      dibenzylimidazol-2-ylidene (= Bn(2)Im)] are prepared by transmetallation
      reactions of (tht)AuBr (tht = tetrahydrothiophene) and (NHC)AgBr (2a/2b). The
      homoleptic, ionic complexes [(NHC)(2)Au]Br (6a/6b) are synthesized by the
      reaction with free carbene. Successive oxidation of 3a/3b and 6a/6b with bromine
      gave the respective (NHC)AuBr(3) (4a/4b) and [(NHC)(2)AuBr(2)]Br (7a/7b) in good
      overall yields as yellow powders. All complexes were characterized by NMR
      spectroscopy, mass spectrometry, elemental analysis and single crystal X-ray
      diffraction. Reactions of the Au(III) complexes towards anionic ligands like
      carboxylates, phenolates and thiophenolates were investigated and result in a
      complete or partial reduction to a Au(I) complex. Irradiation of the Au(III)
      complexes with UV light yield the Au(I) congeners in a clean photo-reaction.

PMID- 21879095
TI  - Hexameric subphthalocyanine rosette.
AB  - A highly congested hexameric subphthalocyanine array was synthesized by axial
      chlorine-to-phenoxy substitution of a hexakis(4-hydroxyphenyl)benzene based
      subphthalocyanine, and photoinduced symmetry-breaking charge separation was
      demonstrated in polar solvent.

PMID- 21879096
TI  - Sampling approaches to predict urban street noise levels using fixed and
      temporary microphones.
AB  - Requirements for static (prediction of L(den) and diurnal averaged noise pattern)
      and dynamic (prediction of 15 min and 60 min evolution of L(Aeq) and statistical
      levels L(A90,)L(A50) and L(A10)) noise level monitoring are investigated in this
      paper. Noise levels are measured for 72 consecutive days at 5 neighboring streets
      in an inner-city noise measurement network in Gent, Flanders, Belgium. We present
      a method to make predictions based on a fixed monitoring station, combined with
      short-term sampling at temporary stations. It is shown that relying on a fixed
      station improves the estimation of L(den) at other locations, and allows for the
      reduction of the number of samples needed and their duration; L(den) is estimated
      with an error that does not exceed 1.5 dB(A) to 3.4 dB(A) according to the
      location, for 90% of the 3 * 15 min samples. Also the diurnal averaged noise
      pattern can be estimated with a good accuracy in this way. It was shown that
      there is an optimal location for the fixed station which can be found by short
      term measurements only. Short-term level predictions were shown to be more
      difficult; 7 day samples were needed to build models able to estimate the
      evolution of L(Aeq,60min) with a RMSE ranging between 1.4 dB(A) and 3.7 dB(A).
      These higher values can be explained by the very pronounced short-term variations
      appearing in typical streets, which are not correlated between locations. On the
      other hand, moderately accurate predictions can be achieved, even based on short
      term sampling (a 3 * 15 minute sampling duration seems to be sufficient for many
      of the accuracy goals set related to static and dynamic monitoring). Finally, the
      method proposed also allows for the prediction of the evolution of statistical
      indicators.

PMID- 21879097
TI  - Occurrence of chlorinated and brominated polycyclic aromatic hydrocarbons in
      surface sediments in Shenzhen, South China and its relationship to urbanization.
AB  - One hundred and fourteen surface sediments were collected from the Maozhou River
      Watershed in Shenzhen, China from December 2009 to January 2010. Three individual
      chlorinated polycyclic aromatic hydrocarbons (ClPAHs), six individual brominated
      polycyclic aromatic hydrocarbons (BrPAHs), and five corresponding parent
      polycyclic aromatic hydrocarbons (PAHs) were determined. The concentration of 9
      chlorophenanthrene was the highest ranging from 0.51-289 ng g(-1) (average, 16.5
      ng g(-1)). For BrPAHs, the concentration of 2-bromofluorene was the highest
      ranging from 0.31-266 ng g(-1) (average, 35.3 ng g(-1)). No correlation was
      observed between the concentrations of ClPAHs and parent PAHs in surface
      sediments. In addition, there was no correlation between 1-bromopyrene, 7
      bromobenz(a)anthracene and 9,10-dibromoanthracene, and corresponding parent PAHs.
      However, a significant correlation was found between 9-bromophenanthrene and
      phenanthrene (p < 0.01), between 9-bromoanthracene and anthracene (p < 0.05), and
      between 2-bromofluorene and fluorene (p < 0.05). Six fly ash samples collected
      from one of the municipal domestic waste incineration plants in Shenzhen were
      also analyzed for source identification. The concentration of 7
      bromobenz(a)anthracene was the highest, ranging from 3.21-4.08 ng g(-1). In
      addition, 2-bromofluorene was not detected in all the fly ash samples. No
      correlation was found between the concentrations of Cl-/BrPAHs and corresponding
      parent PAHs in fly ashes. We also examined the relationship between the levels of
      Cl-/BrPAHs in surface sediments and the urbanization process. Our results
      suggested the levels of individual Cl-/BrPAHs congeners presented a similar
      increasing trend with the increasing urbanization level.

PMID- 21879098
TI  - The role of 'Big Society' in monitoring the state of the natural environment.
AB  - Environmental monitoring is essential for assessing the current state of the
      environment, measuring impacts of environmental pressures and providing evidence
      to government. Recent UK government announcements have indicated an increased
      role for 'Big Society' in monitoring. In this paper, we review available
      literature concerning the use of citizen science for monitoring, present examples
      of successful volunteer monitoring work and highlight important issues
      surrounding the use of volunteers. We argue that in order to ensure that
      environmental monitoring continues to be effective it is important to learn from
      examples where volunteers are currently used, acknowledging constraints and
      identifying potential approaches which will help to maximise both their
      engagement and data quality. Effective partnerships between environmental
      monitoring organisations and volunteers may thus aid the UK in developing robust
      coordinated monitoring systems that will be less vulnerable to funding variances.

PMID- 21879099
TI  - Polyphenols prevent lipid abnormalities and arterial dysfunction in hamsters on a
      high-fat diet: a comparative study of red grape and white persimmon wines.
AB  - SCOPE: We compared the effects of two dealcoholized wines, persimmon (P) and
      Merlot (M), in hypercholesterolemic hamsters. METHODS AND RESULTS: Four groups of
      hamsters received a standard (ST) or an atherogenic diet (AT) for 12 weeks. AT
      animals received either dealcoholized persimmon wine (AT + P) or Merlot wine (AT
      + M) by gavage, while controls received water (AT and ST). Plasma cholesterol,
      triglycerides and glucose and paraoxonase activity were measured. Oxidative
      stress was assessed by aortic O(2) degrees (-) production, and vascular function
      was evaluated in aortic rings. The atherogenic diet led to higher plasma
      triglycerides (246%), total cholesterol (142%), LDL-cholesterol (91%) and HDL
      cholesterol (49%). Aortic production of O(2) degrees (-) also increased (207%)
      and vascular reactivity was modified with altered endothelial function as
      assessed by acetylcholine-dependent vasorelaxation. The two wines partially
      prevented these alterations, reducing O(2) degrees (-) production and improving
      vascular reactivity without altering endothelial function. There was no
      difference between the P and M groups, although the procyanidin composition of
      the two dealcoholized fractions differed significantly, and only dimer
      concentrations were similar. CONCLUSION: These findings indicate that polyphenols
      are responsible, at least in part, for the antiatherogenic/antioxidant effects of
      wines.

PMID- 21879100
TI  - Plant food supplement (PFS) market structure in EC Member States, methods and
      techniques for the assessment of individual PFS intake.
AB  - The popularity of herbal products, especially plant food supplements (PFS) and
      herbal medicine is on the rise in Europe and other parts of the world, with
      increased use in the general population as well as among specific subgroups
      encompassing children, women or those suffering from diseases such as cancer. The
      aim of this paper is to examine the PFS market structures in European Community
      (EC) Member States as well as to examine issues addressing methodologies and
      consumption data relating to PFS use in Europe. A revision of recent reports on
      market data, trends and main distribution channels, in addition an example of the
      consumption of PFS in Spain, is presented. An overview of the methods and
      administration techniques used to assess individual food consumption as a
      starting point, including their uses and limitations, as well as some examples of
      studies that collect Food Supplement (FS) information, including
      herbal/botanical/plant-derived products are also discussed. Additionally, the
      intake estimation process of food nutrients is described and used to propose the
      PFS ingredients intake estimation process. Nationally representative PFS
      consumption data is scarce in Europe. The majority of studies have been conducted
      in Scandinavia and the UK. However the heterogeneity of definitions, study design
      and objectives make it difficult to compare results and extrapolate conclusions.

PMID- 21879101
TI  - The immediate and short-term chemosensory impacts of coffee and caffeine on
      cardiovascular activity.
AB  - The immediate and short-term chemosensory impacts of coffee and caffeine on
      cardiovascular activity. INTRODUCTION: Caffeine is detected by 5 of the 25
      gustatory bitter taste receptors (hTAS2Rs) as well as by intestinal STC-1 cell
      lines. Thus there is a possibility that caffeine may elicit reflex autonomic
      responses via chemosensory stimulation. METHODS: The cardiovascular impacts of
      double-espresso coffee, regular (130 mg caffeine) and decaffeinated, and
      encapsulated caffeine (134 mg) were compared with a placebo-control capsule.
      Measures of four post-ingestion phases were extracted from a continuous recording
      of cardiovascular parameters and contrasted with pre-ingestion measures.
      Participants (12 women) were seated in all but the last phase when they were
      standing. RESULTS: Both coffees increased heart rate immediately after ingestion
      by decreasing both the diastolic interval and ejection time. The increases in
      heart rate following the ingestion of regular coffee extended for 30 min.
      Encapsulated caffeine decreased arterial compliance and increased diastolic
      pressure when present in the gut and later in the standing posture. DISCUSSION:
      These divergent findings indicate that during ingestion the caffeine in coffee
      can elicit autonomic arousal via the chemosensory stimulation of the gustatory
      receptors which extends for at least 30 min. In contrast, encapsulated caffeine
      can stimulate gastrointestinal receptors and elicit vascular responses involving
      digestion. CONCLUSION: Research findings on caffeine are not directly applicable
      to coffee and vice versa. The increase of heart rate resulting from coffee
      drinking is a plausible pharmacological explanation for the observation that
      coffee increases risk for coronary heart disease in the hour after ingestion.

PMID- 21879102
TI  - Natural salicylates: foods, functions and disease prevention.
AB  - Salicylic acid and related compounds are produced by plants as part of their
      defence systems against pathogen attack and environmental stress. First
      identified in myrtle and willow, the medical use of salicylate-rich preparations
      as anti-inflammatory and antipyretic treatments may date back to the third
      millennium BC. It is now known that salicylates are widely distributed throughout
      the plant kingdom, and they are therefore present in plant products of dietary
      relevance. In the UK, major food sources are tomato-based sauces, fruit and fruit
      juice, tea, wine, and herbs and spices. In mammalian cells, salicylic acid
      demonstrates several bioactivities that are potentially disease-preventative,
      including the inhibition of production of potentially neoplastic prostaglandins,
      which arise from the COX-2 mediated catalysis of arachidonic acid. Moreover, it
      appears to be readily absorbed from the food matrix. This has led some to
      suggestions that the recognised effects of consuming fruit and vegetables on
      lowering the risk of several diseases may be due, in part, to salicylates in
      plant-based foods. However, published estimates of daily salicylic acid intake
      vary markedly, ranging from 0.4 to 200 mg day(-1), so it is unclear whether the
      Western diet can provide sufficient salicylates to exert a disease-preventative
      activity. Some ethnic cuisines that are associated with lowered disease risk may
      contain considerably more salicylic acid than is obtainable from a Western diet.
      However known protective effects of acetylsalicylic acid (AspirinTM) may have
      lead to an over-emphasis on the importance of dietary salicylates compared with
      other bioactive plant phenolics in the diet.

PMID- 21879103
TI  - Effective pressure and bubble generation in a microfluidic T-junction.
AB  - To improve the existing trial-and-error process in designing a microfluidic T
      junction, a systematic study of the geometrical (mainly the channel length)
      effects on the generated bubbly/slug flow was conducted to figure out basic
      design guidelines based on experimental and theoretical analyses. A driving
      system with dual constant pressure sources, instead of the commonly used dual
      constant volume-rate sources (such as two syringe pumps), was chosen in this
      study. The newly proposed effective pressure ratio (P(e)*) has revealed its
      advantages in excluding the surface tension effect of fluids. All the data of
      generated bubbly/slug flow for a given geometry collapse excellently into the
      same relationship of void fraction and effective pressure ratio. This
      relationship is insensitive to the liquid viscosity and the operation range is
      strongly affected by the geometrical effect, i.e., the channel length ratio of
      downstream to total equivalent length of the main channel in a T-junction chip.
      As to the theoretical design and analysis of gas-liquid-flow characteristics in a
      microfluidic T-junction, which is still sporadic in the literature, the proposed
      semi-empirical model has successfully predicted the operation boundaries and the
      output flow rate of bubbly/slug flow of different investigated cases and
      demonstrated its usability.

PMID- 21879104
TI  - Rapid detection of algal toxins by microfluidic immunoassay.
AB  - Herein we report fabricating a microfluidic device to monitor harmful algal
      blooming (HAB). The heterogeneous immuno-enzyme assay was integrated into a self
      designed microfluidic chip for rapid and automatic analysis of algal toxins. The
      device was made from polydimethylsiloxane (PDMS) and was assembled with a home
      made control system. The performance of the system was demonstrated by the
      detection of microcystin, saxitoxin and cylindrospermopsin, the major
      cyanotoxins. In one single microfluidic chip, multiple samples were controlled
      and analysed in a parallel manner. Under the optimal conditions, the linear range
      and the limit of detection of microcystins were 0-5.0 ng mL(-1) and 0.02 ng mL(
      1) respectively. The total analysis time was less than 25 min. The designed
      device was highly automatic, more efficient and economic compared to conventional
      techniques.

PMID- 21879105
TI  - A microfluidic in situ analyzer for ATP quantification in ocean environments.
AB  - We have developed and tested a functionally integrated in situ analyzer, the IISA
      ATP system, for microbial activity assays based on a quantitative determination
      of the total (particulate and dissolved) ATP in ocean environments. The IISA-ATP
      utilizes a PDMS-glass hybrid microfluidic device as its core functional element,
      which can perform cell lysis and total ATP quantification by a luciferin
      luciferase bioluminescence assay in situ. Transparent heaters and a temperature
      sensor fabricated on a glass substrate provide temperature control. As a result
      of the evaluation using the microfluidic device with ATP standard solutions, the
      bioluminescence intensity was linearly correlated with 2 * 10(-12) to 2 * 10(-8)
      M of ATP. A detection limit of 1.1 * 10(-11) M was determined using the completed
      IISA-ATP system, which includes a miniature pumping module and a control module.
      As a result of the evaluation using the environmental seawater sample collected
      from Tokyo Bay, Japan, 2.7 * 10(-10) M of total ATP was successfully determined
      in the laboratory by the IISA-ATP. The system was operated at a shallow submarine
      hot spring area in Okinawa, Japan for an in situ trial. The result shows the
      system was successfully operated in situ and the total ATP was determined to be
      3.4 * 10(-10) M.

PMID- 21879106
TI  - The cell monolayer trajectory from the system state point of view.
AB  - Time-lapse microscopic movies are being increasingly utilized for understanding
      the derivation of cell states and predicting cell future. Often, fluorescence and
      other types of labeling are not available or desirable, and cell state
      definitions based on observable structures must be used. We present the
      methodology for cell behavior recognition and prediction based on the short term
      cell recurrent behavior analysis. This approach has theoretical justification in
      non-linear dynamics theory. The methodology is based on the general stochastic
      systems theory which allows us to define the cell states, trajectory and the
      system itself. We introduce the usage of a novel image content descriptor based
      on information contribution (gain) by each image point for the cell state
      characterization as the first step. The linkage between the method and the
      general system theory is presented as a general frame for cell behavior
      interpretation. We also discuss extended cell description, system theory and
      methodology for future development. This methodology may be used for many
      practical purposes, ranging from advanced, medically relevant, precise cell
      culture diagnostics to very utilitarian cell recognition in a noisy or uneven
      image background. In addition, the results are theoretically justified.

PMID- 21879107
TI  - Interactome-wide prediction of short, disordered protein interaction motifs in
      humans.
AB  - Many of the specific functions of intrinsically disordered protein segments are
      mediated by Short Linear Motifs (SLiMs) interacting with other proteins. Well
      known examples include SLiMs that interact with 14-3-3, PDZ, SH2, SH3, and WW
      domains but the true extent and diversity of SLiM-mediated interactions is
      largely unknown. Here, we attempt to expand our knowledge of human SLiMs by
      applying in silico SLiM prediction to the human interactome. Combining data from
      seven different interaction databases, we analysed approximately 6000 protein
      centred and 1600 domain-centred human interaction datasets of 3+ unrelated
      proteins that interact with a common partner. Results were placed in context
      through comparison to randomised datasets of similar size and composition. The
      search returned thousands of evolutionarily conserved, intrinsically disordered
      occurrences of hundreds of significantly enriched recurring motifs, including
      many that have never been previously identified (). In addition to True Positive
      results for at least 25 different known SLiMs, a striking number of "off-target"
      proteins/domains also returned significantly enriched known motifs. Often, this
      was due to the non-independence of the datasets, with many proteins sharing
      interaction partners or contributing interactions to multiple domain datasets.
      The majority of these motif classes, however, were also found to be significantly
      enriched in one or more randomised datasets. This highlights the need for care
      when interpreting motif predictions of this nature but also raises the
      possibility that SLiM occurrences may be successfully identified independently of
      interaction data. Although not as compositionally biased as previous studies,
      patterns matching known SLiMs tended to cluster into a few large groups of
      similar sequence, while novel predictions tended to be more distinctive and less
      abundant. Whether this is due to ascertainment bias or a true functional
      composition bias of SLiMs is not clear and warrants further investigation.

PMID- 21879108
TI  - Conformational propensities and residual structures in unfolded peptides and
      proteins.
AB  - Ample evidence gathered over the last ten years indicates that unfolded and
      naturally disordered proteins and peptides can show local order in that short
      segments can adopt turn or polyproline II-like conformations. These findings show
      that unfolded states cannot be described by the so-called random coil model which
      assumes that individual amino acid residues sample the entire sterically
      accessible parts of the Ramachandran with very similar probabilities. This
      article reviews the experimental evidence for the notion that amino acid residues
      have different propensities for polyproline II, beta-strand, helical and turn
      conformations in water. These propensities are changed by interactions with
      nearest neighbours. We show that for a substantial number of residues the
      conformational propensities in the unfolded state correlate with values for helix
      propagation and the Chou-Fasman propensities for beta-strands. Based on the
      presented results we hypothesize that the conformational distributions of a
      representative set of short peptides could be used for predicting structural
      distributions of disordered peptides and proteins in the future.

PMID- 21879109
TI  - Bisphosphonates as radionuclide carriers for imaging or systemic therapy.
AB  - Bisphosphonates (BP's), biologically stable analogs of naturally occurring
      pyrophosphates, became the treatment of choice for pathologic conditions
      characterized by increased osteoclast-mediated bone resorption, namely Paget's
      disease, osteoporosis and tumor bone disease. Moreover, the clinical success of
      BP's is also associated with their use in (99m)Tc-based radiopharmaceuticals for
      bone imaging. In addition to the successful delivery of (99m)Tc (gamma-emitter)
      to bone, BP's have also been used to deliver beta(-)-particle emitting
      radiometals (e.g.(153)Sm, (186/188)Re) for bone-pain palliation. The main goal of
      this Review is to update the most recent research efforts toward the synthesis,
      characterization and biological evaluation of novel BP-containing radiometal
      complexes and radiohalogenated compounds for diagnostic or therapeutic purposes.
      The structure and in vivo properties of those compounds will be discussed and
      compared to the clinically available ones, namely in terms of image quality and
      therapeutic effect. We will also mention briefly the use of BP's as carriers of
      multimodal nuclear and optical imaging probes.

PMID- 21879110
TI  - Comparative genomics suggests differential deployment of linear and branched
      signaling across bacteria.
AB  - A major mode of signal transduction in bacteria is the two-component system,
      which involves phosphorylation of an output-generating receiver protein by a
      signal-sensing histidine kinase. This differs from the more common one-component
      system--where both signal sensing and output generation are performed by the same
      protein--in the spatial separation of the two activities and the obligate need
      for post-translational modification (phosphorylation). Many described two
      component systems involve a linear structure where a single kinase phosphorylates
      a cognate receiver. However, inherently branched network structures are being
      increasingly discovered, though their prevalence is unknown. Though the simpler
      one-component systems are more common than two-component systems, some organisms
      encode a disproportionately high number of the latter; though these organisms are
      generally described as having 'complex' lifestyles, no systematic description of
      their signaling networks has been proposed. Finally, the relative contributions
      of the two modes of signal transduction towards achieving an optimal regulatory
      cost for growth and survival in an environment remain poorly understood. Here we
      present a comparative genomics survey of ~165,000 regulatory proteins from ~850
      prokaryotic genomes and suggest that organisms with elevated occurrence of two
      component systems--which generally belong to phylogenetic classes with relatively
      poor representation in genomic databases--also code for more complex and branched
      two-component networks. Such branched signaling might compensate for the apparent
      paucity in the total number of regulatory proteins these organisms encode.
      Finally, such interconnected signaling networks might be more common than
      anticipated, indicating the pressing need for genome-scale experimental studies
      of signaling networks in many understudied phylogenetic groups of organisms.

PMID- 21879111
TI  - Evaluation of heavy metal toxicity in eukaryotes using a simple functional assay.
AB  - Although carcinogenesis caused by metals has been intensively investigated, the
      mechanisms of action, especially at the molecular level, are still unclear. This
      work aimed to investigate Cd(2+), Cu(2+), Ni(2+), Cr(3+), and Zn(2+) mutagenicity
      and its relationship with oxidative stress. We have applied the Functional Assay
      for the Separation of Alleles in Yeast (FASAY) with only minor modifications to
      detect p53 defects caused by metals. In this method, human p53-coding gene (TP53)
      expressed in Saccharomyces cerevisiae activates transcription of the ADE2
      reporter gene. Yeast cells, expressing p53, were exposed to increased
      concentrations of metals and, then, plated on media supplemented or not with
      adenine. Yeast colonies containing functional p53 grow independently of adenine
      supplementation and colonies containing nonfunctional p53 are dependent on this
      nutrient. Mutations in the TP53 are implicated in the pathogenesis of half of all
      human tumors. According to our results, Cd(2+) was found to be the most toxic
      metal and produced the highest oxidative damage to lipids and proteins. At low
      concentrations (40 MUM), this metal decreased viability and completely inhibited
      cell growth, while higher concentrations were necessary to produce the same toxic
      effect by Cu(2+), Cr(3+), and Ni(2+). Zn(2+) showed no significant toxicity.
      Cd(2+) strongly induced damages and altered the function of p53, while Cu(2+),
      followed by Cr(3+), showed lower percentages of p53-mutant colonies. Our results
      point towards a relationship between the loss of functional p53 protein and
      oxidative stress, a mechanism that can be associated with tumor formation induced
      by heavy metals in mammalian cells. By this adaptation of FASAY developed by us
      it is possible to easily and rapidly detect mutations caused by metals or other
      stresses.

PMID- 21879116
TI  - Li ion battery materials with core-shell nanostructures.
AB  - Nanomaterials have some disadvantages in application as Li ion battery materials,
      such as low density, poor electronic conductivity and high risk of surface side
      reactions. In recent years, materials with core-shell nanostructures, which was
      initially a common concept in semiconductors, have been introduced to the field
      of Li ion batteries in order to overcome the disadvantages of nanomaterials, and
      increase their general performances in Li ion batteries. Many efforts have been
      made to exploit core-shell Li ion battery materials, including cathode materials,
      such as lithium transition metal oxides with varied core and shell compositions,
      and lithium transition metal phosphates with carbon shells; and anode materials,
      such as metals, alloys, Si and transition metal oxides with carbon shells. More
      recently, graphene has also been proposed as a shell material. All these core
      shell nanostructured materials presented enhanced electrochemical capacity and
      cyclic stability. In this review, we summarize the preparation, electrochemical
      performances, and structural stability of core-shell nanostructured materials for
      lithium ion batteries, and we also discuss the problems and prospects of this
      kind of materials.

PMID- 21879117
TI  - Encapsulation of gold nanoparticles by simian virus 40 capsids.
AB  - Viral capsid-nanoparticle hybrid structures constitute a new type of
      nanoarchitecture that can be used for various applications. We previously
      constructed a hybrid structure comprising quantum dots encapsulated by simian
      virus 40 (SV40) capsids for imaging viral infection pathways. Here, gold
      nanoparticles (AuNPs) are encapsulated into SV40 capsids and the effect of
      particle size and surface ligands (i.e. mPEG and DNA) on AuNP encapsulation is
      studied. Particle size and surface decoration play complex roles in AuNP
      encapsulation by SV40 capsids. AuNPs >=15 nm (when coated with mPEG750 rather
      than mPEG2000), or >=10 nm (when coated with 10T or 50T DNA) can be encapsulated.
      Encapsulation efficiency increased as the size of the AuNPs increased from 10 to
      30 nm. In addition, the electrostatic interactions derived from negatively
      charged DNA ligands on the AuNP surfaces promote encapsulation when the AuNPs
      have a small diameter (i.e. 10 nm and 15 nm). Moreover, the SV40 capsid is able
      to carry mPEG750-modified 15-nm AuNPs into living Vero cells, whereas the mPEG750
      modified 15-nm AuNPs alone cannot enter cells. These results will improve our
      understanding of the mechanisms underlying nanoparticle encapsulation in SV40
      capsids and enable the construction of new functional hybrid nanostructures for
      cargo delivery.

PMID- 21879118
TI  - Continuous electrodeposition for lightweight, highly conducting and strong carbon
      nanotube-copper composite fibers.
AB  - Carbon nanotube (CNT) fiber is a promising candidate for lightweight cables. The
      introduction of metal particles on a CNT fiber can effectively improve its
      electrical conductivity. However, the decrease in strength is observed in CNT
      metal composite fibers. Here we demonstrate a continuous process, which combines
      fiber spinning, CNT anodization and metal deposition, to fabricate lightweight
      and high-strength CNT-Cu fibers with metal-like conductivities. The composite
      fiber with anodized CNTs exhibits a conductivity of 4.08 * 10(4)-1.84 * 10(5) S
      cm(-1) and a mass density of 1.87-3.08 g cm(-3), as the Cu thickness is changed
      from 1 to 3 MUm. It can be 600-811 MPa in strength, as strong as the un-anodized
      pure CNT fiber (656 MPa). We also find that during the tensile tests there are
      slips between the inner CNTs and the outer Cu layer, leading to the drops in
      electrical conductivity. Therefore, there is an effective fiber strength before
      which the Cu layer is robust. Due to the improved interfacial bonding between the
      Cu layer and the anodized CNT surfaces, such effective strength is still high, up
      to 490-570 MPa.

PMID- 21879119
TI  - Preferential synthesis and isolation of (6,5) single-wall nanotubes from one
      dimensional C60 coalescence.
AB  - The (6,5) single-wall carbon nanotubes have been preferentially synthesized from
      a one-dimensional array of C(60) inside single-wall carbon nanotubes (d? 1.5 +/-
      0.1 nm). The as-produced inner tubes have been extracted via sonication and
      density gradient ultracentrifugation methods and demonstrated to be dominated by
      (6,5) tubes by optical absorption, Raman scattering, photoluminescence, high
      resolution transmission electron microscope observation, and a semi-empirical
      simulation (PM3).

PMID- 21879120
TI  - Carbon nanotubes grown in situ on graphene nanosheets as superior anodes for Li
      ion batteries.
AB  - Graphene and carbon nanotubes are intriguing alternative anode materials for
      lithium ion batteries. The prevention of graphene restacking and facilitation of
      lithium diffusion into CNTs with large aspect ratio are highly desirable for the
      performance enhancements including capacity, cycliability and rate capability. In
      this work, we demonstrated that a multilayered graphene-CNT hybrid nanostructure
      was able to hold such merits. GNS were separated and stabilized by CNTs grown in
      situ on GNS surface. The length of CNTs was found to be a key factor to the
      electrochemical performances. The GNS-CNT composite with the shortest CNT
      decoration displayed highly reversible capacities of 573 mAh g(-1) at a small
      current of 0.2C and 520 mAh g(-1) at a large current of 2C. The growth and
      lithium storage mechanism for graphene-CNT composite was also proposed.

PMID- 21879121
TI  - Low temperature crystallization of transparent, highly ordered nanoporous SnO2
      thin films: application to room-temperature hydrogen sensing.
AB  - High surface area highly ordered nanoporous thin films are the current gold
      standard for gas sensor use, however the nanostructure of such films is prone to
      collapse at annealing temperatures as low as 250  degrees C resulting in
      formation of a dense layer of limited utility. We report on a templating method
      used to deposit highly ordered nanoporous platinum (Pt)-doped tin dioxide
      (SnO(2)) thin films that are crystallized by a 100  degrees C water vapor
      hydrothermal treatment, with the low temperature process being compatible with a
      large variety of substrates including plastic. The resulting highly ordered
      nanoporous, transparent Pt-SnO(2) thin films are mechanically stable and can be
      annealed, as desired, at temperatures up to 800  degrees C for removal of the
      templating materials and tailoring of gas sensitivities without damage to the
      nanoporous structure. The synthesis method is general, offering a promising
      strategy for preparing high performance nanoporous metal oxide crystalline films
      for applications including gas sensing, photocatalysis, and 3(rd) generation
      photovoltaics. In our example application of the synthesized materials, we find
      that these Pt-SnO(2) films exhibit exceptional hydrogen gas sensing behavior,
      rapidly detecting low-level hydrogen concentrations at room temperature; for
      example, an eight order of magnitude change in electrical resistance is seen in
      response to 10 000 ppm H(2), with only minimal sensitivity to humidity.

PMID- 21879122
TI  - A thermolysis approach to simultaneously achieve crystal phase- and shape-control
      of ternary M-Fe-O metal oxide nanoparticles.
AB  - Significant studies have achieved beautiful control in particle size, while the
      shape- and phase-control synthesis of nanoparticles remains an open challenge. In
      this study, we have developed a generalized methodology to selectively prepare
      either NaCl-type (reduced form) or spinel-type ferrite (oxidized form) M-Fe-O (M
      = Mn, Co) crystallites with high reproducibility. A two-step heating process was
      able to control formation of two types of crystal phase, either a thermodynamic
      spinel-type under air or a kinetic-control of NaCl-type (rock salt structure)
      under Ar in a cubic morphology. On the other hand, the three-step heating
      procedure in air obtained the spinel-type with a thermodynamic equilibrium
      octahedral shape exclusively. Either using metal acetates (M(ac)(2)) or metal
      acetylacetonates (M(acac)(2)) as the starting precursors (M = Mn, Co) can be
      introduced to prepare NaCl-type (reduced form) or spinel-type ferrite (oxidized
      form) crystallites with identical experimental parameters, including precursor
      concentration, reaction temperature, reaction time, and heating rate. The oleic
      acid molecule, reaction temperature, and heating rate employed in the synthesis
      were carefully examined and found acting as determined roles behind the reaction
      processes. Apart from the previous literature reports as shape-directed and/or
      stabilizing agents, the oleic acid molecule played an additional phase-tuning
      role.

PMID- 21879123
TI  - Nanoscale phase separation in coated Ag nanoparticles.
AB  - In this paper we report the structural investigation of cysteine and glutathione
      capped Ag nanoparticles (NPs) by means of transmission electron microscopy (TEM),
      synchrotron X-ray diffraction (XRD) and pair distribution function (PDF)
      analysis. The combined use of these probes allowed us to observe the presence of
      two crystal structures in the coated AgNPs, i.e., the cubic and the hexagonal
      crystal structures of Ag. In particular, it was possible to demonstrate that the
      coated AgNPs are a nanoscale phase separated system where the two phases coexist
      within the single grain. In addition, the relative bulk amount of the fcc and hcp
      phases has been estimated and a possible correlation with the capping agent
      proposed.

PMID- 21879124
TI  - Naphthalene- and perylenediimides with hydroquinones, catechols, boronic esters
      and imines in the core.
AB  - The green-fluorescent protein of the jellyfish operates with the most powerful
      phenolate donors in the push-pull fluorophore. To nevertheless achieve red
      fluorescence with the same architecture, sea anemone and corals apply oxidative
      imination, a process that accounts for the chemistry of vision as well. The
      objective of this study was to apply these lessons from nature to one of the most
      compact family of panchromatic fluorophores, i.e. core-substituted
      naphthalenediimides (cNDIs). We report straightforward synthetic access to
      hydroxylated cNDI and cPDI cores by palladium-catalyzed cleavage of allyloxy
      substituents. With hydroxylated cNDIs but not cPDIs in water-containing media,
      excited-state intramolecular proton transfer yields a second bathochromic
      emission. Deprotonation of hydroquinone, catechol and boronic ester cores
      provides access to an impressive panchromism up to the NIR frontier at 640 nm.
      With cNDIs, oxidative imination gives red shifts up to 638 nm, whereas the
      expanded cPDIs already absorb at 754 nm upon deprotonation of hydroquinone cores.
      The practical usefulness of hydroquinone cNDIs is exemplified by ratiometric
      sensing of the purity of DMF with the "naked eye" at a sensitivity far beyond the
      "naked nose". We conclude that the panchromatic hypersensitivity toward the
      environment of the new cNDIs is ideal for pattern generation in differential
      sensing arrays.

PMID- 21879125
TI  - Chiral ionic liquid-mediated photochirogenesis. Enantiodifferentiating
      photocyclodimerization of 2-anthracenecarboxylic acid.
AB  - Enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid (AC
      H) and its lithium salt (AC-Li) in chiral ionic liquid (CIL), (R)-1-(2,3
      dihydroxypropyl)-3-methylimidazolium acetate {[(R)-GLYMI][AcO]}, gave a mixture
      of two head-to-tail (HT) and two head-to-head (HH) cyclodimers in HT/HH ratios of
      1.3-1.7 (for AC-H) and 2.2-4.3 (for AC-Li) with low enantiomeric excesses (ee) of
      0-3% for chiral syn-HT and anti-HH dimers. In contrast, irradiation of AC-H in an
      aqueous solution, containing cucurbit[8]uril (CB[8]) as a host and [(R)
      GLYMI][AcO] or [(R)-GLYMI][Tf(2)N] as a modifier of CB portals, afforded the HH
      dimers in 91-99% selectivity, although the anti-HH dimer was totally racemic.
      Interestingly, irradiation of AC-H in a dichloromethane solution, containing [(R)
      GLYMI][AcO] as a chiral template, led to the formation of the HH-dimers in 98%
      selectivity with chiral anti-HH dimer in -14% ee, presumably by the dual ligation
      of two ACs to a CIL through electrostatic and hydrogen-bonding interactions.

PMID- 21879126
TI  - Microwave-assisted chemical ligation of S-acyl peptides containing non-terminal
      cysteine residues.
AB  - An efficient approach for the synthesis of a series of S-acyl peptides containing
      internal cysteine residues has been developed and the chemical long-range
      ligation of these S-acyl peptides via 5-, 8-, 11- and 14-membered cyclic
      transition states has been investigated. Our results include the first examples
      of successful isopeptide ligations starting from S-acyl peptides containing non
      terminal cysteine residues and indicate that the cyclic transition states studied
      in this present paper are decreasingly favored in the order of their sizes
      5?14>11?8.

PMID- 21879127
TI  - Tandem reactions initiated by copper-catalyzed cross-coupling: a new strategy
      towards heterocycle synthesis.
AB  - Copper-catalyzed cross-coupling reactions which lead to the formation of C-N, C
      O, C-S and C-C bonds have been recognized as one of the most useful strategies in
      synthetic organic chemistry. During past decades, important breakthroughs in the
      study of Cu-catalyzed coupling processes demonstrated that Cu-catalyzed reactions
      are broadly applicable to a variety of research fields related to organic
      synthesis. Representatively, employing these coupling transformations as key
      steps, a large number of tandem reactions have been developed for the
      construction of various heterocyclic compounds. These tactics share the
      advantages of high atom economics of tandem reactions as well as the broad
      tolerance of Cu-catalyst systems. Therefore, Cu-catalyzed C-X (X = N, O, S, C)
      coupling transformation-initiated tandem reactions were quickly recognized as a
      strategy with great potential for synthesizing heterocyclic compounds and gained
      worldwide attention. In this review, recent research progress in heterocycle
      syntheses using tandem reactions initiated by copper-catalyzed coupling
      transformations, including C-N, C-O, C-S as well as C-C coupling processes are
      summarized.

PMID- 21879128
TI  - Cyclopenta[c]selenophene based cooligomers and their polymers: comparative study
      with thiophene analogues.
AB  - Selenophene and thiophene capped cyclopenta[c]selenophenes were synthesized and
      characterized. Crystal structure determination of some representative compounds
      revealed that the substitution at 3,4-position in the form of cyclopentane ring
      of selenophene or thiophene does not make any significant twist in the trimer
      backbone, making the cooligomer nearly planar. All the cooligomers were
      electrochemically polymerized and compared with thiophene capped
      cyclopenta[c]thiophene polymer. DFT calculations predict that the cyclopentane
      substitution on the third repeating unit (and in general) of one dimensional
      polymer neither disturb the planarity nor causes any significant twist on the
      polymeric backbone unlike the 3,4-dialkyl substitution. The electrochemically
      prepared selenophene based polymers showed low band gap compared to that of
      thiophene analogues. Cyclopentane substitution on selenophene as well as
      thiophene makes the resulting polymer oxidatively more stable when compared to
      more familiar poly-ethylenedioxythiophene (PEDOT) or poly
      ethylenedioxyselenophene (PEDOS) systems. Alternate polymers of
      cyclopenta[c]selenophenes (CPS)/cyclopenta[c]thiophene (CPT) and
      thiophene/selenophene possess the energy of HOMO and LUMO significantly lower
      than that of homopolymers of CPS and CPT, however, possess higher band gap than
      PCPS.

PMID- 21879129
TI  - Peptide dendrimer enzyme models for ester hydrolysis and aldolization prepared by
      convergent thioether ligation.
AB  - Peptide dendrimers with multiple histidines or N-terminal prolines efficiently
      catalyze ester hydrolysis or aldol reactions in aqueous medium. Part of the
      catalytic proficiency of these dendritic enzyme models stems from multivalency
      effects observed in G2, G3 and G4 dendrimers displaying multiple catalytic groups
      in their branches. To study multivalency in higher generation systems, G4, G5 and
      G6 peptide dendrimers were prepared by a convergent assembly. Thus, peptide
      dendrimers bearing four or eight chloroacetyl groups at their N-termini underwent
      multiple thioether ligation with G2 and G3 peptide dendrimers with a cysteine
      residue at their focal point, to give G4, G5 and G6 dendrimers containing up to
      341 amino acids, including multiple histidines or N-terminal prolines. While the
      efficiency of the esterase catalysts was comparable to that of their lower
      generation analogs, a remarkable reactivity increase was observed in G5 and G6
      aldolase dendrimers.

PMID- 21879130
TI  - A neutral redox-switchable [2]rotaxane.
AB  - A limited range of redox-active, rotaxane-based, molecular switches exist,
      despite numerous potential applications for them as components of nanoscale
      devices. We have designed and synthesised a neutral, redox-active [2]rotaxane,
      which incorporates an electron-deficient pyromellitic diimide (PmI)-containing
      ring encircling two electron-rich recognition sites in the form of
      dioxynaphthalene (DNP) and tetrathiafulvalene (TTF) units positioned along the
      rod section of its dumbbell component. Molecular modeling using MacroModel guided
      the design of the mechanically interlocked molecular switch. The binding
      affinities in CH(2)Cl(2) at 298 K between the free ring and two electron-rich
      guests--one (K(a) = 5.8 * 10(2) M(-1)) containing a DNP unit and the other (K(a)
      = 6.3 * 10(3) M(-1)) containing a TTF unit--are strong: the one order of
      magnitude difference in their affinities favouring the TTF unit suggested to us
      the feasibility of integrating these three building blocks into a bistable
      [2]rotaxane switch. The [2]rotaxane was obtained in 34% yield by relying on
      neutral donor-acceptor templation and a double copper-catalysed azide-alkyne
      cycloaddition (CuAAC). Cyclic voltammetry (CV) and spectroelectrochemistry (SEC)
      were employed to stimulate and observe switching by this neutral bistable
      rotaxane in solution at 298 K, while (1)H NMR spectroscopy was enlisted to
      investigate switching upon chemical oxidation. The neutral [2]rotaxane is a
      chemically robust and functional switch with potential for applications in device
      settings.

PMID- 21879131
TI  - Syntheses of sulfur and selenium analogues of pachastrissamine via double
      displacements of cyclic sulfate.
AB  - Bioisosteric analogues of pachastrissamine that contain sulfur and selenium atoms
      replacing the oxygen in the ring system, were efficiently prepared from a cyclic
      sulfate intermediate by sequential intermolecular and intramolecular S(N)2
      displacement reactions of the dianions. The analogues exhibited cytotoxicities
      comparable to that of pachastrissamine.

PMID- 21879132
TI  - Alloxazine-cyclodextrin conjugates for organocatalytic enantioselective
      sulfoxidations.
AB  - Four structurally different alloxazine-cyclodextrin conjugates were prepared and
      tested as catalysts for the enantioselective oxidation of prochiral sulfides to
      sulfoxides by hydrogen peroxide in aqueous solutions. The alloxazinium unit was
      appended to the primary face of alpha- and beta-cyclodextrins via a linker with
      variable length. A series of sulfides was used as substrates: n-alkyl methyl
      sulfides (n-alkyl = hexyl, octyl, decyl, dodecyl), cyclohexyl methyl sulfide,
      tert-butyl methyl sulfide, benzyl methyl sulfide and thioanisol. alpha
      Cyclodextrin conjugate having alloxazinium unit attached via a short linker
      proved to be a suitable catalyst for oxidations of n-alkyl methyl sulfides,
      displaying conversions up to 98% and enantioselectivities up to 77% ee. beta
      Cyclodextrin conjugates were optimal catalysts for the oxidation of sulfides
      carrying bulkier substituents; e.g. tert-butyl methyl sulfide was oxidized with
      quantitative conversion and 91% ee. Low loadings (0.3-5 mol%) of the catalysts
      were used. No overoxidation to sulfones was observed in this study.

PMID- 21879133
TI  - Claisen rearrangements of equilibrating allylic azides.
AB  - Equilibrating mixtures of allylic azide-containing allylic alcohols or allylic 2
      tolylsulfonylacetic esters undergo Johnson-Claisen or Ireland-Claisen
      rearrangement reactions to give unsaturated gamma-azidoesters and -acids,
      respectively. Decarboxylation of the acids under basic conditions gives
      azidosulfones, with moderate to high diastereoselectivity.

PMID- 21879134
TI  - Practical three-component synthesis of crowded arenes with donor-acceptor
      substitution.
AB  - An operationally simple two-step synthesis of substituted anilides has been
      developed. The methodology utilizes carboxamides, aldehydes, and olefins (or
      alkynes) as cheap starting materials and relies upon the sequential combination
      of condensation, cycloaddition, and oxidation reactions. The intermediate
      cycloadducts display various functional groups (e.g. Br, OAc, NR(2), COR, Cbz)
      for further chemical manipulation at the ring periphery or core. Upon oxidation
      with MnO(2), highly crowded anilides with up to four further substituents (alkyl,
      aryl, carboxylate, cyano, nitro, bromo) can be prepared in good overall yields.

PMID- 21879135
TI  - Total synthesis of clavaminol A, C and H.
AB  - The first total synthesis of clavaminol A and C, (2R,3S)-2-amino-3-alkanols from
      the Mediterranean ascidian Clavelina phlegraea has been achieved in 29% overall
      yield. The key step involved a palladium(II)-catalysed directed Overman
      rearrangement to create the C-N bond and install the erythro configuration while
      a one-pot, tributyltin hydride-mediated reduction allowed simultaneous formation
      of the methyl side-chain and N-acetyl group. Similarly, the first total synthesis
      of clavaminol H was completed in 48% overall yield using an approach that also
      provided the cytotoxic des-acetyl analogue.

PMID- 21879136
TI  - Multifunctional small molecule for controlled assembly of oligomeric
      nanoparticles and crosslinked polymers.
AB  - One multifunctional small molecule can undergo a natural condensation reaction
      under the control of reducing agent to generate amphiphilic oligomers which
      quickly self-assemble supramolecular nanoparticles or form crosslinked,
      reversibly degradable polymers.

PMID- 21879137
TI  - Reinvestigation of the C5-acetamide sialic acid donor for alpha-selective
      sialylation: practical procedure under microfluidic conditions.
AB  - Despite the previous literature describing the "low-to-modest" efficiency, the
      readily available C5-acetamide donor was reinvestigated for its use in alpha
      sialylation under microfluidic conditions. The N-phenyltrifluoroacetimidate donor
      was efficiently mixed with an appropriate amount of TMSOTf to produce the alpha(2
      6) and alpha(2-3)-sialylation products of galactose and glucosamine acceptors in
      excellent yields and with nearly perfect alpha-selectivity.

PMID- 21879139
TI  - A versatile Tb(III) complex for picosecond filamentation, a transparent thin film
      and a supramolecular gel.
AB  - The first complex picosecond filament, namely a filament of terbium(III) p
      hydroxybenzoate, is observed. The filament is the only example of Ln(III) ion two
      photon absorption in a complex. A transparent, colorless and mechanically robust
      thin film, as well as a supramolecular gel, of this complex are prepared in a
      facile manner and exhibit strong luminescence. The thin film is characterized in
      detail by XRD, SEM, UV-vis, luminescence spectroscopy and lifetime.

PMID- 21879138
TI  - Synthesis and characterization of cell-permeant 6-nitrodibenzofuranyl-caged IP3.
AB  - We have synthesized in a 6-nitrodibenzofuranyl (NDBF) derivative of inositol
      1,4,5-trisphosphate (IP(3)) for efficient two-photon uncaging in living cells. As
      its hexakis acetoxymethyl ester, this caged compound may be applied at low
      concentration to the extracellular milieu to load the intact astrocytes in
      acutely isolated brain slices from the mouse cortex. Two-photon irradiation of
      single astrocytes evoked intracellular calcium signals that required 10% of the
      energy dosage compared to nitroveratyl (NV)-IP(3). Since NDBF-IP(3) has a 5-fold
      higher quantum yield than NV-IP(3), these data imply that photolysis of the new
      NDBF caged compound mobilized intracellular calcium about twice as efficiently as
      the NV cage.

PMID- 21879140
TI  - Continuous protein production in nanoporous, picolitre volume containers.
AB  - The synthetic manufacture of functional proteins enables a bottom-up
      understanding of the workings of biological systems and opens new opportunities
      for the treatment of disease. Cell-free protein synthesis is a practical approach
      for enabling such manufacturing, however, it is typically carried out in fairly
      large volumes, when compared to a natural cell, leading to increases in cost and
      loss of efficiency. Here we demonstrate continuous cell free protein synthesis in
      arrays of cellular scale containers that continuously exchange energy and
      materials with their environment. A multiscale fabrication process allows the
      monolithic integration of nanoporous silicon containers within an addressable
      microfluidic network. Synthesis of enhanced green fluorescent protein (eGFP) in
      the containers continues beyond 24 h and yields more than twice the amount of
      protein, on a per volume basis, than conventional scale batch reactions. By
      mimicking the physical volume and controlled flux of a natural cell, the
      resulting "cell mimic" devices can enable fundamental studies of biological
      systems as well as serve applications related to the functional screening of
      proteins and the on-demand production of biologics.

PMID- 21879141
TI  - Production of rapidly reversible antibody and its performance characterization as
      binder for continuous glucose monitoring.
AB  - To effectively control diabetes, a method to reliably measure glucose
      fluctuations in the body over given time periods needs to be developed. Current
      glucose monitoring systems depend on the substrate decomposition by an enzyme to
      detect the product; however, the enzyme activity significantly decays over time,
      which complicates analysis. In this study, we investigated an alternative method
      of glucose analysis based on antigen-antibody binding, which may be active over
      an extended period of time. To produce monoclonal antibodies, mice were immunized
      with molecular weight (M(W)) 10K dextran chemically conjugated with keyhole
      limpet hemocyanin. Since dextran contains glucose molecules polymerized via a 1,6
      linkage, the produced antibodies had a binding selectivity that could
      discriminate biological glucose compounds with a 1,4-linkage. Three antibody
      clones with different affinities were screened using the M(W) 1K dextran-bovine
      serum albumin conjugates as the capture ligand. Among the antibodies tested, the
      antibody clone Glu 26 had the lowest affinity (K(A) = 3.56 * 10(6) M(-1)) and the
      most rapid dissociation (k(d) = 1.17 * 10(-2) s(-1)) with the polysaccharide
      immobilized on the solid surfaces. When glucose was added to the medium, the
      sensor signal was inversely proportional to the glucose concentration in a range
      between 10 and 1000 mg dL(-1), which covered the clinical range. Under the
      optimal conditions, the response time was about 3 min for association and 8 min
      for dissociation based on a 95% recovery of the final equilibrium.

PMID- 21879142
TI  - Enantiorecognition ability of peptoids with alpha-chiral, aromatic side chains.
AB  - The enantiorecognition ability of oligomeric N-substituted glycines or "peptoids"
      with alpha-chiral, aromatic side chains was investigated by HPLC and (1)H NMR
      studies.

PMID- 21879143
TI  - Structural rearrangements of Ru nanoparticles supported on carbon nanotubes under
      microwave irradiation.
AB  - The structure evolution of twinned Ru nanoparticles supported on carbon nanotubes
      rearranging into Ru single nanocrystals under the microwave irradiation and the
      exposed surface of Ru single crystals were observed, which provided new insights
      into synthesis and application of metal nanoparticle catalysts.

PMID- 21879144
TI  - [Pet ownership and health status of pets from immunocompromised children, with
      emphasis in zoonotic diseases].
AB  - OBJECTIVE: To characterize pet ownership and pet health status in families of
      immunocompromised (IS) children, with emphasis in zoonotic diseases. POPULATION
      AND METHODS: Families of IS children from two hospitals in Santiago, Chile, were
      interviewed and their pets were evaluated by veterinary examination,
      coproparasitologic and skin dermatophytes test. In specific cases, other
      laboratory tests were performed in IS children or their relatives. RESULTS: 47
      out of 70 contacted families had pets, 42 participated in the study. Several risk
      factors for IS children were observed, as having a turtle as a pet and to clean
      cat or turtle faeces. Lack of adequate veterinary control, immunizations and
      deparasitation of pets were observed. Some animals showed zoonotic diseases or
      agents, as Brucella canis, Cryptosporidium sp, Giardia intestinalis, Toxocara
      canis and scabies. 44% of dogs had ticks and 37% had fleas, both potential
      vectors of infections. CONCLUSIONS: Our results suggest that policies to provide
      safer pet contact in IS children are needed.

PMID- 21879145
TI  - [Bacteremia and endarteritis cases secondary to Campylobacter spp. in a
      metropolitan hospital: our experience along a quarter of a century].
AB  - Six cases of bacteremia and one of endarteritis were identified between 1986 and
      2010 in a general hospital in Chile. Five of these cases occurred during the
      second half of this timeframe, Campylobacter fetus predominated (5 out of 7) and
      the majority of the infections presented during warmer months. The mean age was
      32.4 years (range 19 to 63) all had comorbidities, and main clinical
      manifestations included fever with diarrhea. Four patients developed hypotension
      and two septic shock. The latter, associated to C. fetus bacteremia, died before
      microbiological diagnosis. Six out of 7 patients received antimicrobial therapy.
      During 2004 and 2010, the rates of Campylobacter spp. positive stool cultures in
      the same hospital increased 4 times, suggesting an emerging profile. Bacteremia
      and endarteritis by Campylobacter spp. can develop in vulnerable patients and
      manifest as fever with or without diarrhea. Finding curved or spiral shaped gram
      negative rods in blood cultures leads to suspect this pathogen. Species
      identification is of utmost importance due to antimicrobial resistance especially
      in C. jejuni. Prognosis is unfavorable due to host characteristics, and case
      fatality rate is high.

PMID- 21879146
TI  - [Infection due to Strongyloides stercoralis: epidemiological, clinical, diagnosis
      findings and outcome in 30 patients].
AB  - BACKGROUND: Strongyloides stercoralis is a nematode parasite, which is endemic in
      tropical and subtropical regions. Infection usually remains asymptomatic, but in
      immunocompromised hosts severe and life-threatening manifestations such as
      hyperinfection syndrome and disseminated disease might occur. METHODS: We
      retrospectively analyzed the epidemiological and clinical characteristics,
      including HIV co-infection, microbiological findings, and outcome in 30 patients
      with strongyloidiasis, who attended in the Infectious Diseases F. J. Muniz
      Hospital in Buenos Aires from January 2004 to December 2008. RESULTS: The study
      included 20 men and 10 women with an average age of 33 years. HIV co-infection
      was present in 21 patients (70%) with a median CD4 T cell count of 50 cells/mm3
      (range 7-355) (average 56 cells/mm3). Among HIV negative patients the following
      comorbidities were detected: tuberculosis (n = 3) and chronic alcoholism, leprosy
      treated with corticosteroids, immunosuppressive treatment for psoriasis, and
      diabetes mellitus (each in one patient). Two patients did not have any
      predisposing diseases or immunosuppressive treatments. Seventeen patients
      presented with diarrhea and were classified as chronic intestinal
      strongyloidiasis (57%), asymptomatic infection with peripheral eosinophilia was
      diagnosed in 7 (23%), and 6 patients (20%) developed hyperinfection syndrome.
      Seventeen patients (57%) presented peripheral eosinophilia. Diagnosis was
      achieved by direct visualization of larvae in feces by Baermann technique (n =
      20), by multiple stool smears examinations (n = 2), by combination of both (n =
      1), by visualization of the filariform larvae in duodenal fluid and stool (n =
      1), and in fecal and bronchoalveolar lavage specimens (n = 6). Overall mortality
      in this series was 20% (6/30). There was no significant correlation between age
      and mortality. A significant inverse correlation between the survival rate and
      CD4 T-cell count as well as eosinophilia was observed. There was also a
      significant correlation between HIV co-infection and mortality. Twenty-two
      patients responded favorably to treatment with ivermectin.

PMID- 21879147
TI  - [Epidemiological description of rabies reservoir in bats in the Metropolitan
      Region: Chile. 2000-2009].
AB  - In Chile, in 1985 rabies was detected in insectivorous bats. Since then the
      epidemiological surveillance activities was extended to these species and the
      epidemiological pattern was characterized as endemic in bats. In this study we
      analyzed positive rabies cases in the Metropolitan Region between 2000 and 2009.
      We identified 325 cases of rabies in 11.472 analyzed samples. We determined an
      increase of positivity cases in bats between the years of the study. Places with
      the highest number of positives cases were Las Condes, Santiago, Providencia,
      Puente Alto and Nunoa. In 147 cases we identify the circumstances in which the
      bat was found: 89 inside, 45 outside the building and 13 in public spaces. In 39
      cases there was contact with humans or animals. These results reinforce the
      relevance of educating the population against the contact with bats and allow
      health authorities to take early surveillance and control measures.

PMID- 21879150
TI  - [Tuberculous meningitis: tips for diagnosis and proposals for treatment].
AB  - Diagnosis of tuberculous meningitis (TBM) is always a challenge. We must give
      importance for duration of clinical manifestations. Cerebrospinal fluid (CSF) has
      own characteristic and it have to be control several times during the treatment.
      Adenosin deaminase with cut off more than 15 UI/mL and M. tuberculosis polymerase
      chain reaction in CSF are the most relevant diagnostic tests. Radiologic test
      gives diagnostic clues but do not confirm the diagnosis. In the future we can
      structure a score with all these elements to support the clinician in the
      diagnostic process. The treatment of TBM because of its high morbidity and high
      mortality has to be necessarily more intensive and prolonged and we must select
      drugs with a good penetration into the central nervous system (SNC). A
      therapeutic scheme with duration of 12 months with two phases is proposed, the
      diary phase during the first three months of treatment includes isoniacid,
      rifampicin, pirazinamid and ethambutol or moxifloxacin. Streptomycin must not be
      included due to own erratic SNC penetration and its known toxicity. The second
      twice a week phase has to be changed by a three times per week phase during 9
      months and it must include isoniacid, rifampicin and pirazinamide. Dexamethasone
      is added during the first 6 weeks of treatment. Patients with HIV infection than
      required treatment with antiretroviral drugs have to start ART treatment when
      diary phase has finished and must not include protease or integrase inhibitors.

PMID- 21879149
TI  - [Colonization of the oral cavity by group mutans streptococci according to age
      assessed by a semi-quantitative method in saliva].
AB  - OBJECTIVE: To evaluate the colonization of group mutans streptococci according to
      age, measuring the amount of bacteria in saliva with a semi-quantitative method
      in a population attended in public and private dental centers of the Metropolitan
      Region, Santiago, Chile. PATIENTS AND METHODS: Saliva samples were obtained from
      14,649 patients aged 5 to 40 years, in one public and 5 private dental centers.
      Bacteria concentration was estimated by the comparison with a standard counting
      chart. The concentration of group mutans streptococci in saliva was test by a 3
      way ANOVA. RESULTS: Bacterial concentration of Streptococcus mutans related with
      the age of patients was significant (p < 0.001). Bacterial concentration in the
      preschool age was 4,7 x 10(5) CFU/mL at 5 years, while 6,0 x10(5) CFU/mL at 12
      years of age, with a decrease in patients over 30 years. Bacterial concentration
      was significantly different in the six centers of the study. CONCLUSIONS: The
      semi-quantitative method was useful to determine the colonization by
      Streptococcus mutans according to age. This could help for identifying population
      at high risk of dental caries and to develop oral health prevention programs in
      specific populations.

PMID- 21879151
TI  - [Neuropsychological evaluation, psychosocial factors, and psychiatric comorbidity
      of children with HIV infection].
AB  - Antiretroviral therapy has marked a change in the course of HIV infection, posing
      new challenges to improve quality of life in pediatric patients. OBJECTIVE: The
      goal of this paper was to identify psychosocial aspects of HIV-infected children
      and adolescents, and to evaluate their neuropsychological development and
      psychiatric co-morbidity. PATIENTS AND METHODS: A descriptive study was
      conducted, evaluating the neurocognitive performance of patients attending at the
      Pediatric Department of Instituto de Medicina Tropical Pedro Kouri of La Habana,
      Cuba, between February and July of 2008. For that purpose, interviews to the
      patients and their relatives were done with the application of appropriate tests
      for each age. RESULTS: Twenty-three patients ages 3-17 years (57% female) were
      studied. Sixteen (69.5%) were infected through vertical transmission, and 7
      (30.5%) through other routes. School children infected through vertical
      transmission showed the most symptoms. Hyperactivity, anxiety, and learning
      disorders were the most frequently observed symptoms as well as hyperkinetic
      disorders, temporary tic disorders and mental retardation. CONCLUSION: This study
      shows the neuropsychological characterization of HIV-positive children and
      adolescents, considering the route of acquisition of the infection and the stage
      of the disease. It also describes psychiatric comorbidity of HIV-infected
      children.

PMID- 21879152
TI  - [Arcanobacterium bernardiae].

PMID- 21879153
TI  - [Neonatal herpes simplex encephalitis: two twins, two cases].
AB  - Herpes simplex encephalitis is an infrequent infection with high mortality and
      morbidity. Antiviral therapies decrease mortality but long term sequelae are
      still high, so early diagnosis is important for opportune treatment. We present a
      pair of twins with central nervous system herpes simplex infection during the
      first month of life. Both twins presented non-specific symptoms and consulted
      with 48 hours apart needing intensive care admission, the first one for
      noninvasive mechanical ventilation and the second for hemodynamic support.
      Diagnosis was made by cerebrospinal fluid PCR, in the first twin at day 9 of
      disease and in the second at admission. Both twins were treated with acyclovir,
      but only the second one at the beginning of her illness. Initial study with
      electroencephalogram and magnetic resonance was normal and cerebrospinal fluid on
      day 18 of treatment was negative for herpes simplex virus DNA detection in both
      patients.

PMID- 21879154
TI  - [Cutaneous tuberculosis: two case reports and review].
AB  - Cutaneous tuberculosis is a chronic infectious disease caused by Mycobacterium
      tuberculosis. It is uncommon (1% of all cases of tuberculosis), but has increased
      due to the human immunodeficiency virus epidemic and to pharmacologic
      immunosuppression. It presents a wide variety of clinical forms depending on how
      bacteria reach the skin and on the immune status of the patient. We present two
      cases of cutaneous tuberculosis diagnosed in the Hospital Clinico de la
      Pontificia Universidad Catolica de Chile. We emphasize the difficulty in
      diagnosis and classification of this disease and briefly discuss on the different
      diagnostic and therapeutic approaches.

PMID- 21879155
TI  - [Primary cutaneous mucormycosis: two case reports and review of the literature].
AB  - Mucormycosis or zygomycosis is a rare opportunistic infection caused by aerobic
      saprophytic fungus that belongs to the class of Zygomycetes Mucorales family.
      These organisms live in the environment and enter the body by air,
      gastrointestinal or skin routes, through solutions of continuity of the skin.
      This microorganism is generally not pathogenic for immunocompetent hosts, being
      the development of the disease linked with the immune status of the subject. Its
      mortality is around 50-60%; sometimes in spite of early diagnosis and treatment
      initiation it has a fatal course. Six clinical forms of mucormycosis are
      described: rhinocerebral, cutaneous, pulmonary, disseminated, gastrointestinal
      and miscellaneous form. Two cases of patients with primary cutaneous mucormycosis
      diagnosed in the Pathology Unit of Hernan Henriquez Aravena Hospital of Temuco,
      Chile are presented here.

PMID- 21879156
TI  - [Fast onset cognitive impairment: neuroborreliosis and positive 14-3-3 protein].

PMID- 21879157
TI  - [Aldo Castellani and the expeditions of the Royal Society to the black sleep's
      country].
AB  - At the beginning the investigation on infectious diseases was plenty of
      adventures in exotic countries. The efforts of the English investigators, headed
      by Patrick Manson, gave birth to the "tropical" medicine and "tropical" diseases,
      like the sleeping sickness, which was sweeping the country north to the Victoria
      Lake in 1901. The Royal Society of London sent two Commissions in search of the
      etiological agent. Aldo Castellani was decisive for the failure of the first -
      Low, Castellani, Christy,1902 - because even he saw Trypanosoma in samples of
      some patients, he did not appreciate his discovery; and decisive also for the
      success of the second -Bruce, Nabarro, Greig, 1903 - when he and Bruce recognized
      this Trypanosoma as the etiological agent. Following these expeditions, Low
      developed a brilliant career in England, Christy a life of investigation mixed up
      with adventures through Asia and Africa and Castellani a long life of lights and
      shadows in many lands.

PMID- 21879158
TI  - [Prevalence of zinc and copper deficiencies in older subjects living in
      Metropolitan Santiago].
AB  - BACKGROUND: Older subjects have a high risk of developing zinc and copper
      deficiencies. AIM: To determine the prevalence of copper and zinc deficiencies in
      adults aged over 60 years, living in Metropolitan Santiago. SUBJECTS AND METHODS:
      Analyses were performed using anonymous serum samples from older subjects living
      in Santiago, Chile, who participated in the multicenter project SABE. Of the
      studied subjects, 49.3% had enough left over serum to measure serum zinc and
      copper concentrations by atomic absorption spectrometry. RESULTS: A total of 444
      men and 198 women were studied. A positive correlation between serum zinc and
      copper was found in both women (r = 0.44, p < 0.001) and men (r = 0.48, p <
      0.001). There were no differences in serum zinc concentration by sex and age. The
      prevalence of subnormal serum zinc values was 66.9% in women and 66.7% in men.
      Women had a significantly higher serum copper values than men (p < 0.02) and
      there were no differences by age. Prevalence of subnormal serum copper values was
      higher in women than in men (32.9 and 23.7% respectively, p < 0.05). Women had
      significantly higher copper I zinc serum ratio than men (p < 0.001). CONCLUSIONS:
      Older people living in Metropolitan Santiago have a high prevalence of copper and
      zinc deficiencies.

PMID- 21879159
TI  - [Risk factors for a high carotid intima media thickness among healthy adults].
AB  - BACKGROUND: Carotid intima media thickness (CIMT) is a marker of cardiovascular
      damage that can be modified by traditional risk factors. AIM: To determine
      attributable risk factors for a high CIMT among healthy adults. MATERIAL AND
      METHODS: A sample of 1270 individuals (636 males and 634 females) aged 44 +/- 11
      years, was studied. Blood pressure, weight, height, lipid profile and blood
      glucose were measured in all. CIMT and the presence of atherosclerotic plaques
      were determined by carotid ultrasound. Standard criteria were used to define
      hypertension, dyslipidemia and diabetes. RESULTS: Mean CIMT in the sample studied
      was 0.62 +/- 0.01 mm and percentile 75 was 0.67. The most important risk factor
      for a CIMT over percentile 75 and the presence of atherosclerotic plaques was
      hypertension with attributable risks of 54 and 57%, respectively. CONCLUSIONS: In
      this sample, the main risk factor for a high CIMT was hypertension.

PMID- 21879160
TI  - [Cytogenetic and molecular profile of genetic diseases in Puerto Montt main
      hospital].
AB  - BACKGROUND: Chromosome aberrations (CA) are the main etiology of multiple
      congenital malformations, recurrent abortions and intellectual disability (ID)
      specifically of moderate and severe degree. They account for 0.3 to 1% of
      newborns (NB) and 6 of 10,000 NB have chromosome imbalances with submicroscopic
      deletions or duplications smaller than 10 MB that are overlooked by conventional
      cytogenetic studies. AIM: To report the results of cytogenetic and molecular
      studies performed in patients with a congenital malformation disease or ID with
      or without dysmorphic features, attended in a regional hospital. PATIENTS AND
      METHODS: One hundred and eighty patients, 27 with a clinical diagnosis of Down
      syndrome, derived for the suspicion of a genetic disease, were studied. A
      karyogram was performed in all of them and in 30 cases additional molecular
      studies, such as fluorescence in situ hybridization (FISH) or polymerase chain
      reaction (PCR) were carried out. RESULTS: Among the 153 patients without Down
      syndrome, 20 (13%) had a genetic abnormality responsible for the altered
      phenotype. Sixteen had a chromosome aberration (structural and numerical
      aberrations in 75 and 25% respectively) and four had genetic molecular
      alterations. Additional studies were performed to confirm or better characterize
      the chromosome aberration in 13 of the 30 patients in whom these were requested.
      CONCLUSIONS: Chromosome and specific genetic molecular studies in selected cases
      help to characterize patients with genetic diseases. The collaboration between
      academic and health care facilities is crucial.

PMID- 21879161
TI  - [Association of age with sperm DNA fragmentation].
AB  - BACKGROUND: There is an association between aging ana an increased number of
      sperms with alterations in nuclear DNA. AIM: To study the association between age
      and fragmentation of sperm DNA. MATERIAL AND METHODS: Sixty two volunteers
      provided semen for analysis. These were separated in a group aged less than forty
      years and a second group aged more than forty years. Sperm DNA fragmentation was
      studied by TUNEL (terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine
      5'-triphosphate nick end-labeling) and SCD (sperm chromatin dispersion test)
      assays. RESULTS: Compared with their younger counterparts, patients aged more
      than 40 years had a higher proportion of sperms with DNA fragmentation by TUNEL
      (20 +/- 1.3 and 24 +/- 1.9% respectively, p < 0.05) and SCD (22 +/- 1.4 and 26 +/
      1.6% respectively, p < 0.05). The results of both assays had a correlation
      coefficient of O.8. No differences between groups were observed for other seminal
      parameters. CONCLUSIONS: Sperm DNA fragmentation increases with age in males.

PMID- 21879162
TI  - [Health related quality of life among patients with type 2 diabetes mellitus].
AB  - BACKGROUND: Type 2 diabetes mellitus may affect profoundly the quality of life of
      patients. AIM: To assess health related quality of life among patients with Type
      2 Diabetes Mellitus. MATERIAL AND METHODS: The Diabetes Quality of Life (DQOL)
      questionnaire was applied to 296 patients with diabetes mellitus aged 63 +/- lO
      years (201 women) seen in primary health care centers. RESULTS: The concern about
      the future effects of diabetes was the worst evaluated domain. Women perceived a
      lower health related quality of life than men. There was an inverse correlation
      between age and satisfaction with treatment, concern about vocational, social and
      future effects of the disease. CONCLUSIONS: Type 2 diabetes affects health
      related quality of life, especially in some specific domains such as perception
      of the future.

PMID- 21879163
TI  - [Clinical impact of pandemic influenza A H1N1 in a Chilean regional hospital].
AB  - BACKGROUND: Pandemic flu (H1N1 ) strongly affected southern Chile during 2009.
      AIM: To report the logistic and organizational changes implemented at a regional
      hospital to face the pandemic. MATERIAL AND METHODS: All patients with flu like
      disease that were hospitalized, were prospectively enrolled at the Puerto Montt
      hospital. A nasopharyngeal aspirate was obtained in all for influenza virus A and
      B direct immunofluorescence and polymerase chain reaction (PCR). All
      epidemiological and clinical data of patients were recorded. RESULTS: Between May
      29 and July 7, 2009, 184 adults were admitted to the hospital and in 117 patients
      aged 41 +/- 18 years (56% females ), direct immunofluorescence was positive for
      influenza. In 67 of these patients PCR did not confirm the disease. These
      unconfirmed patients had a mean age of 49 +/- 19 years (p < 0.01, compared with
      confirmed cases) and had a lower frequency of fever, rhinorrhea and chills. No
      significant differences in the incidence of community acquired pneumonia or chest
      X ray findings were observed between confirmed and unconfirmed cases. Hospital
      stay was over 15 days in 14% of confirmed cases and 5% of unconfirmed cases (p =
      0.03). Fifteen patients, aged 53 +/- 18 years, died. CONCLUSIONS: Low sensibility
      of direct immunofluorescence and delay in obtaining PCR confirmation of influenza
      posed a problem for the management of these patients.

PMID- 21879164
TI  - [Changes long term prognosis of 17 patients with pulmonary artery hypertension].
AB  - BACKGROUND: Pulmonary artery hypertension (PAH) is a progressive disease with
      high mortality. Major advances had been made in the treatment of this condition
      during the last decade. AIM: To characterize the clinical evolution and mortality
      of a cohort of Chilean patients. MATERIAL AND METHODS: Seventeen patients with
      PAH diagnosed in the last 10 years in two Chilean hospitals were enrolled.
      Measurements at diagnosis included hemodynamic variables and 6-minute walk test.
      The patients were followed clinically for 3 years and the observed mortality was
      compared with that predicted by the prognostic equation proposed by the historic
      registry of the National Institutes of Health (NIH). RESULTS: The mean age of
      patients was 45 years and 80% had an idiopathic PAH. The mean median pulmonary
      artery pressure was 57 +/- 15 mmHg, the cardiac index was 2.4 +/- 0.7 l/min/m2
      and the right atrial pressure was 12 +/- 8 mmHg. The 6-minute walk distance was
      348 +/- 98 m. All patients received anticoagulants. Eighty two percent received
      ambrisentan, 12% received bosentan, 29% received iloprost and 24% sildenafil. At
      the end of follow-up only 3 patients had died, with an observed survival rate of
      88, 82 and 82% at 1, 2 and 3 years, respectively. In contrast, the survival
      calculated according to the predictive formula of the NIH was 67, 56 and 45%,
      respectively. Among surviving patients, an improvement in exercise capacity was
      observed after one year (p < 0.05). CONCLUSIONS: The observed survival rate was
      significantly better than that estimated according to historical data.
      Furthermore, therapy was associated with an improvement in functional capacity
      after one year. This prognostic improvement is consistent with data of other
      contemporary registries published after the NIH Registry.

PMID- 21879165
TI  - [Hypovitaminosis D in pediatric patients on renal replacement therapy].
AB  - BACKGROUND: Hypovitaminosis D has a high prevalence among patients with chronic
      kidney disease (CKD). AIM: To determine the prevalence of 25 hydroxy vitamin D
      (25(OH) D) insufficiency and deficiency in pediatric patients on dialysis and
      kidney transplantation. MATERIAL AND METHODS: Serum calcium and phosphorus,
      parathormone (PTH), alkaline phosphatases and 25 (OH)D were measured in 13
      children on hemodialysis (HD), 18 on peritoneal dialysis (PD) and 53 that
      received an allograft (Tx), aged 9.8 +/- 4.6 years (51% females). RESULTS: Fifty
      four percent of patients had height Z score less than -1.88. Patients on HD had
      the lowest values. The average time of replacement therapy was 2.9 +/- 2.8 years.
      Mean 25(OH)D levels in all was 18.7 +/- 10.7ng/ml (HD: 21 +/- 16.8, PD: 18.9 +/-
      8.5, Tx: 18.1 +/- 9.72 ng/ml). Eighty eight percent of patients had levels below
      30 ng/ml. Mean of serum calcium was 9.5 +/- 0.64 mg/dl, serum phosphorus 5.03 +/-
      1.02 mg/dl, calcium-phosphorus product 48 +/- 11.8 mg/dl and alkaline
      phosphatases 300.5 +/- 171.3 IU/L. Average PTH values in dialyzed and Tx patients
      were 724.6 +/- 640.5 and 107.7 +/- 56.2 pg/ml, respectively (p < 0.001). A
      positive correlation between 25 (OH) D and calcium levels among PD patients was
      observed (r = 0.490, p = 0.04). CONCLUSIONS: Hypovitaminosis D is highly
      prevalent among children on renal substitution therapy, regardless of the type of
      therapy used and the stage of renal failure.

PMID- 21879167
TI  - [Tako-Tsubo syndrome: report of one case].
AB  - Tako-Tsubo syndrome resembles an acute myocardial infarction in symptoms,
      laboratory parameters and electrocardiographic changes. However, angiography does
      not show evidence of coronary occlusion, and typically an apical ballooning of
      the ventricle in systole is observed. We report a 78-year-old woman with no
      coronary risks factors, admitted to the emergency room due to acute chestpain and
      an electrocardiogram compatible with an acute coronary syndrome with ST
      elevation. Serum troponin and creatin-kinase (MB fraction) were elevated. An
      emergency coronary angiography did not show a coronary occlusion. Due to the
      apical ballooning observed in the left ventriculography, a probable diagnosis of
      Tako-Tsubo was proposed. The patient had a favorable evolution. A treadmill test,
      echocardiogram and myocardial perfusion SPECT, performed one month later,
      disclosed no abnormalities.

PMID- 21879166
TI  - [Validation of the University of Southern California Repeatable Episodic Memory
      test].
AB  - BACKGROUND: Memory is affected differently with the passage of time;
      specifically, episodic memory presents a clear decline. There is a relationship
      of this memory impairment and degenerative and psychiatric diseases. AIM: To
      determine the reliability and validity of the University of Southern California
      Repeatable Episodic Memory Test (USC-REMT) in a sample of Chilean adults.
      MATERIAL AND METHODS: The instrument was administered to 178 subjects living in
      the Metropolitan Region of Santiago. The sessions were individual, during the
      morning, lasting approximately 15 minutes. RESULTS: The ANOVA indicates that
      subjects over 61 years old had lower scores in the test than their younger
      counterparts. There was an inverse correlation between age and success in "Free
      recall" (r =- 0.570), "Recognition indicating yes-no" (r = -0.412) and "forced
      choice recognition" (r =- 0.371). Regression analysis showed that age explained
      32.1 % "free recall" variance. The three components were grouped into a single
      factor. CONCLUSIONS: The USC-REMT meets the criteria for validity and reliability
      to be applied for clinical and research purposes.

PMID- 21879168
TI  - [Trans-esophageal echocardiography in non-cardiac surgery: report of four
      illustrating cases].
AB  - Transesophageal echocardiography can assess ventricular filling ana contraction
      ana detect motility disturbances secondary to ischemia. In non-cardiac surgery it
      can be extremely helpful to monitor complex patients. We report a 69-year-old
      mole subjected to a hepatic lobectomy, a 59-year-old mole with hepatorenal
      syndrome, a 52-year-old female subjected to a gastric bypass, and a 54-year-old
      mole subjected to a thyroidectomy. In these four cases, left ventricular motility
      and preload were evaluated with transesophageal echocardiography, and it was of
      great aid in decision-making during anesthesia.

PMID- 21879169
TI  - [Acquired hemophilia A treated with rituximab. Report of one case].
AB  - We report a 54-year-old male presenting with a history or recurrent nose bleeds
      and ecchymoses. The coagulation study showed a prolonged partial thromboplastin
      time, a factor VIII of 8% and a high inhibitor titer (193 Bethesda units). A
      diagnosis of acquired hemophilia A was reached. The patient was initially treated
      with cyclophosphamide for seven months without response. Therefore rituximab in
      doses of 375 mglm2/week for four weeks was started. After starting treatment, the
      patient had a hematoma in the psoas muscle with a concomitant factor VIII of less
      than 5%, that was treated with local measures. Thereafter, a progressive
      reduction in inhibitor titers was observed, until its disappearance at five
      months of treatment. Factor VIII levels normalized and the patient has not
      experienced abnormal bleeding episodes. The patient remains in remission after 67
      months of follow up. Rituximab, a chimeric monoclonal antibody against the
      protein CD 20 is an effective treatment in acquired hemophilia A.

PMID- 21879170
TI  - [Olfactory sensory perception].
AB  - The five senses have had a fundamental importance for survival and socialization
      of human beings. From an evolutionary point of view the sense of smell is the
      oldest. This sense has a strong representation within the genome, allowing the
      existence of many types of receptors that allow us to capture multiple volatile
      odor producing molecules, sending electrical signals to higher centers to report
      the outside world. Several cortical areas are activated in the brain, which are
      interconnected to form an extensive and complex neural network, linking for
      example, areas involved with memory and emotions, thus giving this sense of
      perceptual richness. While the concept of flavor is largely related to the sense
      of taste, smell provides the necessary integration with the rest of the senses
      and higher functions. Fully understanding the sense of smell is relevant to
      health professionals. Knowing the characteristics of the receptors, the
      transduction processes and convergence of information in the higher centers
      involved, we can properly detect olfactory disorders in our patients.

PMID- 21879171
TI  - [Vasoplegic syndrome and its treatment with vasopressin during cardiac surgery
      with cardiopulmonary bypass].
AB  - Cardiac surgery with cardiopulmonary bypass is associated with systemic
      inflammatory response. In some cases this clinical condition is characterized by
      severe hypotension due to low systemic vascular resistance during and after
      cardiopulmonary bypass. A few of these cases do not respond to volume or
      catecholamines. This condition is known as vasoplegic syndrome. Its etiology is
      not fully understood today and carries associated morbidity and mortality In this
      syndrome, vasopressin levels are reduced, as in septic and hypovolemic shock.
      Supplementary vasopressin improves blood pressure and might be considered as an
      alternative treatment. Several reports have shown benefits when used alone or in
      combination with catecholamines. However, further studies are necessary to find
      the most appropriate use of the drug for vasoplegic syndrome.

PMID- 21879172
TI  - [Treatment and prevention of cancer treatment related oral mucositis].
AB  - One of the most common and troublesome complications of modern intensive
      anticancer treatments is oral mucositis. The purpose of this review is to
      summarize current evidence and clinical guidelines regarding its prevention and
      therapy. The use of keratinocyte growth factor-1, supplementary glutamine and
      other recently developed treatment modalities are discussed. The injury of the
      oral mucosa caused by antineoplastic agents promotes the local expression of
      multiple pro-inflammatory and pro-apoptotic molecules and eventually leads to the
      development of ulcers. Such lesions predispose patients to several infectious and
      nutritional complications. Also, they lead to modification of treatment
      schedules, potentially affecting overall prognosis. Local cryotherapy with ice
      chips and phototherapy with low energy laser may be useful as preventive
      measures. Mouthwashes with allopurinol and phototherapy with low energy laser can
      be used as treatment. In radiotherapy, special radiation administration
      techniques should be used to minimize mucosal injury. Pain control should always
      be optimized, with the use of patient controlled analgesia and topical use of
      morphine. Supplemental glutamine should not be used outside of research
      protocols. Lastly, thorough attention should be paid to general care and hygiene
      measures.

PMID- 21879173
TI  - [Mechanical ventilation in patients with acute brain injury].
AB  - In about 20% of patients admitted to an Intensive Care Unit (ICU) the indication
      of mechanical ventilation (MV) is a neurological disease. These patients have a
      prolonged MV stay and high mortality. The appropriate use of MV in patients with
      acute brain injury (ABI) is critical considering that MV by itself is able to
      induce or worsen an underlying lung injury. Patients with ABI have a higher risk
      to develop pulmonary complications. During endotracheal intubation the activation
      of airway reflexes should be prevented, because they may increase intracranial
      pressure. Tracheostomy is indicated to improve airway management and it is
      performed in about 33% of these patients. Indications for MV are loss of
      spontaneous respiratory effort, changes in lung compliance, gas exchange
      impairment and ventilatory failure due to muscle fatigue or neuromuscular
      junction dysfunction. During MV, hypoxemia should be avoided. The pC0(2) level
      has a critical role in cerebral blood flow regulation; therefore a normal pCO
      must be maintained in order to guarantee an optimal cerebral blood flow. Despite
      that, hypocapnia has been used in patients with increased intracranial pressure,
      at the present it is not recommended. Its use should be limited to the emergency
      management of intracranial hypertension, while the underlying cause is being
      treated. Non-conventional ventilatory modes as prone position ventilation, high
      frequency oscillatory ventilation and extracorporeal C02 removal can be used in
      patients with ABI. All of them have specific risks and should be employed
      cautiously This paper reviews upper airway management and MV in patients with
      acute brain injury.

PMID- 21879174
TI  - [Masters of internal medicine, in Chile].

PMID- 21879175
TI  - [Jonathan Swift's scientific contribution on his "Gulliver's Travels"].
AB  - Jonathan Swift is one of the most celebrated satirist writers in literature. His
      well-known "Gulliver's Travels", apart from being a serious human being
      criticism, contains many interesting ana unrecognized comments about medical and
      other scientific facts. Swift made what seems to be the first account of a
      dementing illness in the elderly; his description fits well with what we now know
      as Alzheimer's disease. He also described a condition now called synaesthesia, a
      very interesting phenomenon that may contribute to creativity. In this paper, we
      review aspects of his life and reveal these amazing descriptions as samples of
      Swift's extraordinary power of observation.

PMID- 21879176
TI  - [Human pregnancy, a biological paradigm of tolerance and adaptation].
AB  - This review analyses the changes in immunological tolerance, and the systemic and
      local hemodynamic changes observed along human pregnancy. To underscore the
      conceptual importance of tolerance and adaptation the background is provided by
      the two main advocates of these ideas: Gandhi and Darwin. The cognate factors
      that determine immunological tolerance (IT), systemic (SA) and local adaptation
      (LA) are multiple; IT = desensitisation to paternal antigens, absence of HLA-A,
      roles of HLA-G, natural killer cells and their receptors; SA = decreased vascular
      resistance, plasma volume expansion, increased cardiac output and plasma renin
      activity; LA = prostacyclin, nitric oxide, kallikrein-kinin system, vasodilator
      arm of the renin angiotensin system, vascular endothelial growth factor (VEGF). A
      possible role of vasodilators in the crucial process of trophoblast invasion and
      uterine artery transformation is supported. The relevance of an adequate
      adaptation to pregnancy is highlighted not only by the intragestational
      complications derived from a defective process, such as intrauterine growth
      restriction, preterm birth, and preeclampsia -its foremost expression- but also
      by the long term cardiovascular complications of the mother and her offspring.

PMID- 21879177
TI  - [Training in Neuropsychiatry: a National need?].

PMID- 21879178
TI  - [Study of resistance to chemotherapy mediated by ABC transporters in biopsies of
      glioblastoma multiforme].
AB  - BACKGROUND: Mortality rate is dramatically high in high grade brain tumors. The
      presence of multiple drug resistance transporters in glioblastoma multiforme, has
      contributed largely to the poor efficacy of targeted therapy against cancer in
      the central nervous system. AIM: To analyze the percentage of survival and
      mortality of patients with glioblastoma multiforme in a cohort of patients in
      Chile and to co-rrelate the chemo-resistance of these cells with the expression
      level of multiple drug resistance transporters. MATERIALS AND METHODS: Eighteen
      biopsies of glioblastoma multiforme were obtained from patients at the Institute
      of Neurosurgery Dr. Asenjo (INCA). The tumor cells were obtained from primary
      cultures and the expression and activity of multiple drug resistance transporters
      was assessed by RT-PCR and immunohistochemistry. Population-based study was
      performed using the databases of the Department of Neurosurgery of INCA. RESULTS:
      The number of patients with glioblastoma multiforme increased between 2007 and
      2009, from 3.5% to 7.9% of total brain tumors. Mortality of these tumors is 90 %
      at three years. A high expression and activity of the multiple drugs resistance
      associated protein 1 (Mrp1) transporter was observed in primary cultures of
      biopsies. CONCLUSIONS: We propose that Mrp1 activity is responsible for the chemo
      resistance of the glioblastoma multiforme and inhibition of this transporter
      could represent a plausible strategy for the treatment.

PMID- 21879179
TI  - [Intake and energy metabolism in a sample of overweight and obese Chilean
      adolescents].
AB  - BACKGROUND: In the last decades, a seven to nine fold increase in the prevalence
      of teenage obesity and overweight has occurred. AIM: To assess energy intake and
      metabolism in a sample of overweight and obese adolescents. MATERIAL AND METHODS:
      In a sample of 113 overweight and obese Chilean adolescents (aged 13 to 16 years,
      67 females) we studied anthropometry, body composition by deuterium isotope
      dilution water, resting energy expenditure by indirect calorimetry and 24-h diet
      and physical activity recalls. RESULTS: Most participants (87% of men and 67.2%
      of women) had an intake that was adequate compared to requirements (fAO/WHO
      2005). However, 82.6% of men and 83.6% of women showed reduced energy
      expenditure. The sample was classified as sedentary, with a physical activity
      level of 1.29. CONCLUSIONS: In our sample of overweight and obese adolescents
      there was a sedentary behavior, resulting in low energy expenditure that would
      explain a sustained caloric retention. Preventive and therapeutic interventions
      should encourage the increase in physical activity.

PMID- 21879180
TI  - [Prognostic factors for gastric cancer without lymph node involvement].
AB  - BACKGROUND: The absence of lymph node involvement (N0) in gastric cancer is
      associated with a better survival. However some N0 gastric tumors still have a
      bad prognosis. AIM: To study demographic and morphological variables associated
      with prognosis in N0 gastric carcinoma. MATERIAL AND METHODS: Review of
      pathological records of a regional general hospital, identifying patients with a
      N0 gastric cancer surgically excised between 1986 and 2003. RESULTS: In the study
      period, 459 gastrectomies were performed for gastric cancer and in 32%, the tumor
      was devoid of lymph node involvement. These later patients were followed for a
      median of 64 months with a 71% five years actuarial survival. Bivariate analysis
      identified age, tumor size, gastric wall infiltration, pathological type
      according to Lauren and Ming, lymphovascular involvement, number of lymph nodes
      excised and TNM stage as prognostic values Multivariate analysis disclosed the
      level of gastric wall infiltration, the presence of a poorly differentiated
      tumor, lymphatic vascular involvement, number of excise lymph nodes and tumor
      size as independent prognostic factors. CONCLUSIONS: N0 gastric tumors are found
      in 32% of gastrectomies for gastric cancer and have a 71% five years actuarial
      survival. Gastric wall infiltration, pathological degree of differentiation tumor
      size and lymphovascular involvement are independent prognostic factors.

PMID- 21879181
TI  - [Rectal ozone therapy for patients with pulmonary emphysema].
AB  - BACKGROUND: Ozone therapy may stimulate antioxidant systems and protect against
      free radicals. It has not been used formerly in patients with pulmonary
      emphysema. AIM: To assess the effects of rectal ozone therapy in patients with
      pulmonary emphysema. MATERIAL AND METHODS: Sixty four patients with pulmonary
      emphysema, aged between 40 and 69 years, were randomly assigned to receive rectal
      ozone in 20 daily sessions, rectal medicinal oxygen or no treatment. Treatments
      were repeated three months later in the first two groups. At baseline and at the
      end of the study, spirometry and a clinical assessment were performed. RESULTS:
      fifty patients completed the protocol, 20 receiving ozone therapy, 20 receiving
      rectal oxygen and 10 not receiving any therapy. At baseline, patients on ozone
      therapy had significantly lower values of forced expiratory volume in the first
      second (fEV1) and fEV1/forced vital capacity. At the end of the treatment period,
      these parameters were similar in the three treatment groups, therefore they only
      improved significantly in the group on ozone therapy. No differences were
      observed in other spirometric parameters. CONCLUSIONS: Rectal ozone therapy may
      be useful in patients with pulmonary emphysema.

PMID- 21879182
TI  - [Source of infection in young infants hospitalized with Bordetella pertussis].
AB  - BACKGROUND: Despite pertussis vaccination, very young infants have the highest
      rates of morbidity and mortality caused by the microorganism. AIM: To determine
      the source of Pertussis infection in infants aged six months or less in Chile.
      MATERIAL AND METHODS: Twenty six household contacts of 10 young infants
      hospitalized with confirmed Pertussis were studied for the presence of Bordetella
      Pertussis by polymerase chain reaction (PCR). Clinical and demographic data were
      analyzed. RESULTS: Respiratory symptoms were present in 20 (77%) contacts, being
      cough the most common. Pertussis cases were identified in every household and in
      18 (72%) of the household members. four members with B.pertussis were
      asymptomatic. Source of infection was identified in 80% (8/10) of the infant
      cases with ages ranging from 6 to 62 years. Half of primary cases had positive
      PCR and their cough duration was significantly shorter compared to primary cases
      with negative PCR. CONCLUSIONS: B. pertussis transmission to young infants
      occurred mainly within the household where adults are generally the source of the
      infection. Risk factors for infant infection are the same as in developed
      countries. Therefore, the same strategies, such as routine vaccination in
      adolescents and adults or cocoon strategy, will help to prevent this disease in
      infants.

PMID- 21879183
TI  - [Assessing a test to evaluate clinical analytical thinking according to medical
      training level].
AB  - BACKGROUND: MATCH (Measuring Analytical Thinking in Clinical Health Care) is an
      instrument to evaluate clinical reasoning. AIM: To assess MATCH performance in
      professionals and students with different training in pediatrics. MATERIAL AND
      METHODS: MATCH was administered to medical students (S), first (R1) and third
      (R3) year residents and staff physicians (P). We evaluated the score and time
      required to achieve it, according to training level in pediatrics. RESULTS:
      Eighty five subjects were included (23 S, 28 R1, 17 R3 y 17 P), achieving 37.4 +/
      6.0 points, in 25.2 +/- 8.5 minutes. There were significant differences in score
      and time, according to training level. There was a positive correlation between
      training level and score (Rho = 0.515; p < 0.001), and a negative one between
      training level and time (Rho = -0.589; p < 0.001). CONCLUSIONS: More experienced
      and trained professionals had a better performance in a clinical analytical
      thinking test.

PMID- 21879184
TI  - [Medical students as members of the health care team].
AB  - BACKGROUND: Teaching hospitals include both undergraduate and postgraduate
      students, but the role of medical students in the health care team has not been
      clearly established. AIM: To know the opinion of different professionals about
      the role of medical students and how this opinion may have an influence in
      medical education. MATERIAL AND METHODS: A qualitative method was used, asking
      open questions to focus groups of physicians, nurses and midwives, technicians
      and undergraduate medical students of 4th and 5th grade. RESULTS: Physicians
      believe that medical students have no special role in the health care team,
      nurses think that they may help in communication with patients, and technicians
      (nurses's aids) value their companionship and closeness with patients. Medical
      students recognize that their main function is to learn but they are aware that
      they do help patients. They suggest increasing their integration with other
      students of other health related careers. CONCLUSIONS: Although medical students
      are usually not seen as part of the health care team, they may fulfill a role
      with patients during their clinical learning practice. This would improve the
      quality of their training and the multidisciplinary work of the health care team.

PMID- 21879185
TI  - [Detection of genes associated with drug resistance in Mycobacterium tuberculosis
      strains isolated in Chile].
AB  - BACKGROUND: The incidence of acquired resistance to antituberculous drugs of
      Mycobacterium tuberculosis in Chile is approximately 23%. AIM: To analyze the
      mutations associated with drug resistance in drug resistant strains of
      Mycobacterium tuberculosis. MATERIAL AND METHODS: In 28 drug resistant
      Mycobacterium tuberculosis strains isolated in Chile, genes leading to drug
      resistance were studied. DNA was amplified by polymerase chain reaction (PCR) and
      sequencing was carried out using the ABI PRISM big dye terminator cycle
      sequencing ready reaction kit. RESULTS: In rifampicin-resistant strains, the
      mutations in rpobeta gene were in the codons S531W/L (56%), D516Y (16%) and D516V
      (16%). The predominant mutation in katG gene was in the codon S315L (73%) in
      isoniazid-resistant strains. The mutation S95T was found in the 71% of
      ciprofloxacin resistant strains. Only one ethambutol resistant strain had the
      M306I mutation. Three unreported mutations in katG were identified. CONCLUSIONS:
      Drug resistance associated mutations of Mycobacterium tuberculosis isolated in
      Chile were similar to those reported abroad.

PMID- 21879186
TI  - [A self administered survey to assess bullying in schools].
AB  - BACKGROUND: Bullying is common in schools and has negative consequences. It can
      be assessed using a self-reported instrument. AIM: To validate a Spanish self
      reporting tool called "Survey of High School Bullying Abuse of Power" (MIAP).
      MATERIAL AND METHODS: The instrument has 13 questions, of which 7 are multiple
      choice, rendering a total of 49 items. It was applied to 2.341 children of
      seventh and eighth grade attending private, subsidized and municipal schools in
      the city of Concepcion, Chile. Expert judge analysis and estimated reliability
      using the Cronbach Alpha were used to validate the survey. RESULTS: The
      instrument obtained a Cronbach Alpha coefficient of 0.8892, classified as good.
      This analysis generated four scales that explained 30.9% of the variance. They
      were called "Witness Bullying" with 18 items, accounting for 11.4% of the
      variance, "Bullying Victim" with 12 items, accounting for 7.5% of the variance,
      "Bullying Perpetrator and Severe bullying Victim", with 10 items explaining 6.4%
      of the variance and "Aggressor Bullying" with 6 items accounting for 5.7% of the
      variance. CONCLUSIONS: The MIAP can recognize four basic factors that facilitate
      the analysis and understanding of bullying, with good levels of reliability and
      validity. The remaining questions also deliver valuable information.

PMID- 21879187
TI  - [Rhabdomyolysis and acute renal failure after cocaine overdose: report of one
      case].
AB  - Rhabdomyolysis caused by cocaine abuse is multifactorial, involving tissue
      ischemia secondary to vasoconstriction and cellular damage caused by the drug.
      Renal failure may or may be not associated to rhabdomyolysis. We report a 41-year
      old male admitted with a severe rhabdomyolysis after a cocaine overdose. In spite
      of a vigorous hydration and alkalization, he developed acute renal failure. Renal
      function recovered after several weeks of dialysis.

PMID- 21879188
TI  - [Remission of vitiligo during treatment with intravenous immunoglobulin: report
      of one case].
AB  - Vitiligo is associated with other autoimmune diseases. We report a 52-year-old
      male with a Sjogren syndrome that was treated with monthly pulses of intravenous
      immunoglobulin for a chronic inflammatory demyelinating polyradiculoneuropathy.
      The neurological disorder responded adequately to the treatment and the patient
      also noted a marked remission of his vitiligo with almost compete re-pigmentation
      of the scalp and face and partial repigmentation of other areas.

PMID- 21879189
TI  - [Retroperitoneal fibrosis associated with chronic use of ergotamine: report of
      one case].
AB  - Retroperitoneal fibrosis (RPF) associated with chronic use of ergotamine is a
      very rare disorder. We report a 45-year-old woman who presented with a RPf after
      using, almost daily for 23 years, ergotamine tartrate for migraine relief. FRP
      presented as a chronic inflammatory state, anemia, abdominal and lumbosacral pain
      and a hypogastric mass. A CT-Scan showed a periaortic mass and left
      hydronephrosis. A percutaneous biopsy was obtained and the patient was subjected
      to a surgical ureterolysis and tissue resection. The biopsy confirmed the
      presence of RPf. Due to persistent symptoms and increase in the volume of
      periaortic tissue, treatment with colchicine 1 mg/day and defazacort 30 mg/day
      was started, resulting in a rapid disappearance of symptoms, disappearance of
      inflammation and a significant reduction in the volume of the periaortic tissue.
      The patient remains in complete remission after 29 months of follow up.

PMID- 21879190
TI  - [International policies towards sick leave: A referent to analyze the Chilean
      situation].
AB  - This is a comparative review of sick leave and wage replacement policies among
      countries of the Organization for Economic Co-operation and Development (EOCD),
      an organism that Chile joined recently. This review also deals with the main
      transformations applied to the system to improve its effciency and the variables
      that explain such changes. The Chilean system is analyzed from the perspective of
      substitution rates, waiting time and protection length. According to these
      parameters, Chile is located below countries such as Scandinavian countries, that
      provide a universal protection, and over those countries that provide a focalized
      protection according to worker's needs.

PMID- 21879191
TI  - [The role of uric acid in heart failure].
AB  - Complications and mortality of heart failure are high, despite the availability
      of several forms of treatment. Uric acid, the end product of purine metabolism
      would actively participate in the pathophysiology of heart failure. However,
      there is no consensus about its action in cardiovascular disease. Serum uric acid
      would have a protective antioxidant activity. This action could help to reduce or
      counteract the processes that cause or appear as a result of heart failure.
      However, these protective properties would vanish in the intracellular
      environment or in highly hydrophobic areas such as atherosclerotic plaques and
      adipose tissue. This review discusses the paradoxical action of uric acid in the
      pathophysiology of heart failure.

PMID- 21879192
TI  - [Developmental toxicity of misoprostol: an update].
AB  - Misoprostol, a synthetic analog of prostaglandin E1, is currently used in Chile
      and other countries as an antiulcer medication, mainly for the prevention of non
      steroidal anti-inflammatory-induced gastric ulcers. Due to its uterotonic
      properties, it is also indicated in obstetrics for induction of labor and
      termination of pregnancy. In this last case, misoprostol is either used alone or
      in combination with other oxytocic drugs such as methotrexate or mifepristone.
      The use of misoprostol as an abortifacient agent is considered to be safe since
      it rarely causes serious side effects. However up to 15 % of misoprostol-induced
      abortions may not be successful, even under medical supervision, leading to in
      utero exposure to the drug and to the induction of a series of birth defects
      including limb and joints defects and Moebius syndrome. Reports from the nineties
      failed to show a strong epidemiological association between in utero drug
      exposure and induction of defects, a situation that has changed now that the
      number of cases reported has increased. Since the practice of abortion is illegal
      in Chile, many women turn to off-medical procedures to interrupt their pregnancy
      and use misoprostol as an easy and cheap alternative, readily available in the
      INTERNET. The lack of medical supervision in these cases may lead to situations
      that favor the induction of congenital defects. Here, we present an updated
      review of scientific data, to evaluate the risk of birth defects in babies
      exposed to the drug during pregnancy termination failed attempts.

PMID- 21879193
TI  - [Medical schools: students today].
AB  - Physicians that are faculty members in medical schools receive new students every
      year, and they are expected to prepare those students to become professionals.
      They usually appeal to their experience to meet that challenge. However, newer
      generations of students are different, and experience, with no formal training
      for teaching them, can be insufficient. New characteristics of students can be
      related to their early contact in life with information technology. Their brain
      has been somehow modified by stimuli offered by this technology, and the way they
      learn has also been modified. This paper is a reflection about how students have
      changed and it analyzes how their learning experience needs to be modified
      accordingly. Teaching based only on experience might be insufficient to fulfill
      the expectations of young students that have chosen the medical profession for
      their future.

PMID- 21879194
TI  - [Bioethics of Sigmund Freud's death: euthanasia or appropriation?].
AB  - The death of Freud raises the ethical dilemma about euthanasia. It can be
      characterized as indirect active euthanasia according to the rule of double
      effect, or terminal sedation, or palliated death. The primacy of the principle of
      autonomy over non maleficence, conditioned the physician's attitude toward his
      patient Freud. The physician assisted death was and remains punishable in western
      medicine. Therefore, a fundamental tradition was infringed. In contrast, the
      present study attempts to characterize the final position of Freud himself to his
      death and called it appropriation of his finitude; he assumes his being-unto
      death, that is, he now projects his being not as a being-at-his-end but as a
      being-unto-end, indicating thereby that he understood that the end always
      penetrated his whole existence.

PMID- 21879195
TI  - [The anatomy Lesson of Dr. Nicolaes Tulp: The beginning of a medical utopia].
AB  - The Anatomy Lesson of Dr. Nicolaes Tulp was painted by Rembrandt Harmen-szoon van
      Rijn at the early age of 26 years. In the XVII century these paintings were very
      popular in the Netherlands, and in this country the cities flourished as cultural
      centers searching the anatomy knowledge. Nicolaes Tulp was one of the persons in
      the center of Amsterdam's scene during XVII century. In 1632 Tulp was 39 years
      old, and he was an anatomist and a surgeon. Rembrandt masterly shows an autopsy
      performed by Dr. Tulp. This picture is the description of the beginning of a
      medical intellectual utopia: the absolute visibility of the disease.
      Unfortunately this utopia is blind to the complete visibility of the psycho-socio
      cultural dimensions of the ill.

PMID- 21879196
TI  - [Basic concepts about paternity testing].
AB  - Nowadays, the analysis of genetic markers is a very important and validated tool
      for the identification of individuals, and for paternity testing. To do so,
      highly variable regions of the human genome are analyzed, making it possible to
      obtain the genetic profile of an individual, and to distinguish between different
      individuals. The methodology used is basically the same all over the world,
      consisting in the analysis of 13 to 15 markers. To assign biological paternity
      the child must have inherited the characteristics from the alleged father in each
      of the genetic markers analyzed. This analysis achieves a certainty higher than
      with any other test, which is expressed as the probability of paternity. This
      probability has to be at least 99.9%, but greater probabilities are usually
      obtained, especially if the mother is included in the analysis. If the
      characteristics of two or more genetic markers from the alleged father are absent
      in the child, biological paternity is excluded.

PMID- 21879197
TI  - [Updated reference values for sperm counts (WHO 2010)].

PMID- 21879198
TI  - [Medical research, Chilean miners and ?Medicine P4?].

PMID- 21879199
TI  - Complement in skin diseases.
AB  - Complement is one of the most important mechanisms of natural resistance
      preventing infections in humans and animals. It is actively involved in the
      pathogenesis of several diseases, including skin diseases, characterized by the
      presence of autoantibodies, foreign microorganisms, altered tissue cells, and the
      presence of mannan. Complement is intended to kill invading microorganisms but it
      can also destroy the organism's own damaged or altered cells. It is characterized
      by vigorous activity and is also potentially harmful for the host if triggered in
      its own body. This review discusses the significance of complement activation for
      emerging skin diseases and highlights the importance of serological laboratory
      tests for the detection of complement system activity alterations in skin
      diseases such as pemphigus vulgaris, bullous pemphigoid, herpes gestationis,
      dermatitis herpetiformis, porphyria, urticaria, angioedema, cutaneous vasculitis,
      systemic lupus erythematosus, partial lipodystrophy, lichen planus, xeroderma
      pigmentosum, psoriasis, and recurrent cutaneous infections. Finally, we draw
      attention to the current potential for treating these diseases with complement
      inhibitors.

PMID- 21879200
TI  - Discontinuing long-term Iloprost treatment for Raynaud's Phenomenon and systemic
      sclerosis: a single-center, randomized, placebo-controlled, double-blind study.
AB  - BACKGROUND: Iloprost has been reported to reduce Raynaud's phenomenon (RP) and to
      inhibit progression of systemic sclerosis (SSc). OBJECTIVE: The aim of our study
      was to compare monthly iloprost infusions with placebo in patients treated long
      term. METHODS: Seventeen patients, six with RP and 11 with SSc on monthly
      treatment with iloprost, received either a 3-hour intravenous infusion of
      iloprost or an equal volume of placebo once per month for 4 months in a
      monocentric, randomized, placebo-controlled, double-blind study. Raynaud attacks
      as measured by diary entries, skin temperature, skin sclerosis, fist closure,
      mouth opening, and digital ulcers were recorded during the observation period.
      RESULTS: Whereas mouth opening improved significantly (p = 0.043) in the iloprost
      treated group, RS improved in both patient groups. However, no significant
      differences were found in the outcome measures. CONCLUSION: Although iloprost
      influences the inflammatory cascade in SSc, no statistical differences were seen
      in our study, indicating that treatment strategies with iloprost should be
      modified.

PMID- 21879201
TI  - Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma.
AB  - The authors decided to evaluate the possible use of methyl-aminolevulinate
      photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell
      carcinoma prior to standard surgical excision in order to reduce tumor size and
      volume and to facilitate surgical treatment. It was observed that MAL-PDT may be
      an option as an adjunctive therapy prior to standard surgical excision of
      morpheaform basal cell carcinoma, leading to less invasive surgery.

PMID- 21879202
TI  - Tufted hair folliculitis: a case report and literature review.
AB  - Tufted hair folliculitis is a rare folliculitis of the scalp that resolves with
      patches of scarring alopecia within multiple hair tufts emerging from dilated
      follicular orifices. Tufting of hair is caused by clustering of adjacent
      follicular units due to a fibrosing process and to retention of telogen hairs
      within a dilated follicular orifice. Various pathogenetic mechanisms have been
      proposed including nevoid abnormalities, recurrent infections of the follicles,
      and retention of telogen hair in the tufts. We present a patient with tufted hair
      folliculitis who was effectively treated with antibacterial medications,
      verifying the infectious nature of the disease.

PMID- 21879203
TI  - Isolated genital annular lichen planus.
AB  - Annular lichen planus is a rarely reported variant of lichen planus (LP).
      Although genital lesions are frequent in patients with LP, isolated genital LP is
      rarely reported. We present a case of a 29-year- -old circumcised man with an
      asymptomatic annular lesion of the penis. Histopathological features were
      consistent with LP. Topical clobetasol was prescribed, with clinical improvement.
      It is important to consider annular LP among the possible diagnoses of individual
      annular genital lesions.

PMID- 21879204
TI  - Pseudoxanthoma elasticum-like papillary dermal elastolysis.
AB  - Elastolysis refers to a loss of elastic fibers. It can affect the papillary
      dermis, the reticular dermis, or both. Pseudoxanthoma elasticum-like papillary
      dermal elastolysis (PXE-PDE) is a clinicopathological entity first described by
      Rongioletti and Rebora in 1992 (1). It is an acquired elastolytic disorder that
      mainly affects the papillary dermis. Clinically it resembles pseudoxanthoma
      elasticum (PXE), but it differs histologically and there is no systemic
      involvement, in contrast to PXE.

PMID- 21879205
TI  - Foscarnet-induced penile ulceration.
AB  - Foscarnet is used to treat herpes viruses, including drug-resistant
      cytomegalovirus (CMV) and herpes simplex viruses types 1 and 2 (HSV-1 and HSV-2).
      There are some reports of intravenous foscarnet-induced penile and vulvar
      ulceration. The authors report a case of the development of severe penile ulcers
      after the initiation of intravenous foscarnet therapy.

PMID- 21879206
TI  - Bilateral idiopathic hyperkeratosis of the nipple and areola.
AB  - Hyperkeratosis of the nipple and areola (HNA) is an unusual dermatosis that Levy
      Franckel classified into three variants (1). This rare condition occurs primarily
      in young women and represents a cosmetic problem. Furthermore, its management is
      a therapeutic challenge. We report on the rare case of a 32-year-old woman with
      idiopathic bilateral HNA, which belongs to the third Levy-Franckel
      classification.

PMID- 21879207
TI  - The need for Singapore resuscitation research and guidelines.

PMID- 21879208
TI  - Implementation of National Resuscitation Guidelines 2006.
AB  - The implementation of guidelines released by the National Resuscitation Council
      in 2006 involved all the main areas of resuscitation, especially basic life
      support and defibrillation. The emphasis was on community training, creation of
      simplified programmes, combining cardiopulmonary resuscitation (CPR) and
      defibrillation, and using simpler training devices. As a result, public access
      defibrillation programmes have been increasingly implemented together with the
      CPR + automated external defibrillator programmes. A large number of instructors
      have also been trained.

PMID- 21879209
TI  - Basic Cardiac Life Support: 2011 Singapore guidelines.
AB  - The core skills required in resuscitation of cardiac arrest individuals is
      referred to as Basic Cardiac Life Support or cardiopulmonary resuscitation (CPR).
      Once cardiac arrest (an unresponsive patient with no breathing or only gasping
      motions) is recognised, chest compressions should be initiated. Healthcare
      workers may choose to also check for a pulse to verify cardiac arrest if they are
      trained. The time taken for breathing check (and pulse check) should not exceed
      ten seconds. Good quality chest compressions are recommended with each being
      delivered with arms extended, elbows locked, shoulders vertically above the
      patient's chest and the heel of the palm on the lower half of the sternum. The
      rescuer should push hard and fast, with a compression of at least 5.0 cm,100
      compressions per minute for adults and allow complete chest recoil after each
      compression. Every 30 chest compressions should be followed promptly by two quick
      and short ventilations (each 400-600 ml tidal volume) delivered within six
      seconds. Chest compression-only CPR is recommended for dispatcher-instructed CPR
      or if the rescuer, for any reason, is unable or unwilling to do mouth-tomouth
      ventilations. CPR should only be stopped when the patient wakes up or an
      emergency team arrives and takes over patient care, or if an automated external
      defibrillator were to prompt interruption of chest compressions for analysis of
      heart rhythm or delivery of shock.

PMID- 21879210
TI  - Defibrillation.
AB  - Defibrillation may be needed in witnessed and unwitnessed cardiac arrests.
      Cardiopulmonary resuscitation (CPR) must be initiated and defibrillation
      administered without delay. Every shock cycle includes 1-2 minutes of CPR
      followed by rhythm analysis. The energy level for biphasic defibrillation of
      ventricular fibrillation is 150 J with possible step-wise escalation to 360 J.
      All healthcare workers need to learn and be authorised to use an automated
      external defibrillator (AED). In addition, all ambulances must be equipped with
      AEDs when transporting patients. Self-adhesive pads/paddles must be applied
      firmly to the skin for best effect. Monitoring electrodes and pacemaker locations
      should be considered during paddle/pad placement. AED skills should be imparted
      to a wide variety of community groups. More efforts will be made to increase the
      availability of AEDs in public, residential, commercial and industrial
      facilities.

PMID- 21879211
TI  - Advanced Cardiac Life Support guidelines 2011.
AB  - The main emphasis in the Advanced Cardiac Life Support (ACLS) guidelines are in
      the areas of good quality chest compressions, ensuring normoventilation, removal
      of atropine from the cardiac arrest algorithm, removal of the use of the
      endotracheal route for drug administration, and renewed focus on the care
      provided after return of spontaneous circulation. In addition, the need for
      monitoring of quality of the various care procedures is emphasised. While the
      various ACLS procedures are being carried out, there is a need to minimise
      interruptions to chest compressions for maintenance of coronary perfusion
      pressures. In addition, the resuscitation team needs to continually look out for
      reversible causes of the cardiac arrest.

PMID- 21879212
TI  - Life support course for nurses in Singapore.
AB  - Nurses are usually the first caregivers for cardiac arrest patients in an in
      hospital environment, and subsequently partner with doctors in the further
      resuscitation of patients. The skills of basic life support are crucial for their
      practice. The Advanced Cardiac Life Support programme is traditionally geared
      toward training of medical staff in advanced resuscitation skills. The need for a
      bridging course that focuses on the knowledge and skills required by nurses to
      become effective members of the resuscitation team has resulted in the creation
      of the Life Support Course for Nurses (LSCN) in Singapore. The components of the
      LSCN programme have evolved over the years, taking into consideration the
      modifications to resuscitation guidelines. The LSCN programme is gradually
      including a larger proportion of nurses in the emergency and critical care
      environments as well as those in the general ward.

PMID- 21879214
TI  - Bystander CPR and survival.
AB  - Despite years of medical advances, bystander cardiopulmonary resuscitation (CPR)
      remains the most important factor in the saving of out-of-hospital cardiac arrest
      victims. However, the prevalence of bystander CPR remains low. New international
      recommendations, which aim to increase bystander CPR prevalence, allow for hands
      only CPR under certain circumstances. More should be done to increase the
      awareness and training of CPR in Singapore as well as encourage the public to
      perform bystander CPR.

PMID- 21879213
TI  - Newborn and paediatric resuscitation 2011 guidelines.
AB  - We present the revised guidelines for newborn and paediatric resuscitation for
      Singapore. The 2010 International Liaison Committee on Resuscitation consensus on
      science as well as the main recommendations from the European Resuscitation
      Council and American Heart Association were debated and discussed. The final
      recommendations for the Singapore National Resuscitation Council were derived
      after carefully reviewing the current available evidence in the literature and
      balancing the local clinical climate of practice. In addition, much effort was
      spent on aligning the paediatric and neonatal recommendations with the adult
      (especially Basic Cardiac Life Support) recommendations.

PMID- 21879215
TI  - Chest compression-only CPR or good quality 30:2 CPR.
AB  - There is debate as to whether chest compression-only cardiopulmonary
      resuscitation (CC-CPR) or standard 30:2 CPR should be taught to laypersons.
      Equivalence in outcomes between standard CPR and CC-CPR has been amply
      demonstrated in communities with short ambulance response times of about five
      minutes. Depriving oxygen from a collapsed patient beyond six minutes results in
      poorer outcomes. Communities with prolonged ambulance travel times have seen
      improved outcomes with CPR than CC-CPR. While healthcare workers demonstrate a
      reluctance to perform mouth-to-mouth ventilation, laypersons generally show a
      willingness to do so. Rescuer fatigue also argues against the use of CC-CPR for
      more than a few minutes. For communities with relatively long ambulance transport
      times, the best approach appears to be standard CPR, with emphasis on good
      quality compression. For dispatcher-assisted CPR, communication issues suggest
      that CC-CPR is advisable. Public CPR training should include teaching of mouth-to
      mouth ventilation alternating with chest compressions.

PMID- 21879216
TI  - Cardiac arrest in the skies.
AB  - Cardiac arrest occurring on board aeroplanes is rare, but remains a common cause
      of inflight incidents. This review examines some of the management problems
      unique to inflight cardiac arrests, and emphasises the use of cardiopulmonary
      resuscitation and automated external defibrillators.

PMID- 21879217
TI  - Improving the quality of CPR in the community.
AB  - Bystander cardiopulmonary resuscitation (CPR) is important for survival from out
      of-hospital cardiac arrest (OHCA). However, recent research indicates that the
      quality of CPR is an important and often overlooked factor affecting survival.
      Individual factors, training, awareness, technique and rescuer fatigue may
      influence the quality of CPR. Quality components of CPR include rate, ratio,
      depth and ventilation-compression ratio. The new 2010 CPR guidelines advocate a
      ratio of compressions to ventilations of 30:2, with a rate of at least 100
      compressions per minute. Depth of compression should be at least 5 cm. Rescuers
      should allow complete recoil of the chest. Locally, limited information is
      available regarding the quality of CPR being performed for OHCA. Strategies to
      improve the quality of CPR include research, training, education as well as
      incorporating appropriate technologies that measure and feedback the quality of
      CPR. These technologies are at the heart of recent advances, as they now make it
      feasible to provide routine feedback to rescuers providing CPR, through the
      integration of feedback devices into training equipment, defibrillators and
      standalone CPR assist devices.

PMID- 21879218
TI  - Mechanical CPR.
AB  - Mechanical devices for cardiopulmonary resuscitation have been in use for
      decades. Significant advances in the understanding of cardiac arrest physiology
      have led to improvements and new devices. Piston, load distribution band, active
      compression decompression and the impedance threshold device are discussed.

PMID- 21879219
TI  - Drugs in resuscitation: an update.
AB  - Drug therapy is recommended after effective cardiopulmonary resuscitation and
      defibrillation in cardiac arrest. Some drugs appear to have short-term benefits,
      such as improved survival to hospital, e.g. vasopressor and antiarrhythmics.
      Hence, they have been included in the cardiac life support algorithm. However, to
      date, no drug (or combination of drugs) has been shown to improve long-term
      survival in randomised trials. Hopefully, improvements in post-arrest intensive
      unit care can translate improved survival in hospitals into better long-term
      outcomes. This review is an update on drugs during resuscitation, including the
      choice of agents, dosing, sequence and route. Specific drugs may have benefits in
      correcting identified causes of collapse. Drug usage during resuscitation is an
      evolving science, with the use of medications improving as results of clinical
      studies become available.

PMID- 21879220
TI  - Controlled hypothermia in post-resuscitation management: what is so cool about
      it?
AB  - Survivors of successful resuscitated cardiac arrest have a high incidence of
      severe neurological deficits. The pathophysiology of cerebral injury is thought
      to be multifactorial, and therapeutic mild hypothermia is one of the strategies
      that have been shown to minimise this complication. In this article, we outline
      the theoretical basis for this strategy as well as the clinical evidence to
      support current practice guidelines advocating its use. We also review the
      technical aspects of implementing hypothermia after resuscitation as well as the
      potential side effects. Finally, unresolved issues are discussed as we outline
      the ongoing prospective clinical trial underway in Singapore in order to evaluate
      its safety and efficacy in our local population. We advocate further research
      into this topic, as it has great potential to improve the outcomes of comatose
      resuscitated patients of cardiac arrest.

PMID- 21879221
TI  - The post-resuscitation bundle.
AB  - Following restoration of pulse after the institution of cardiopulmonary
      resuscitation, defibrillation and perhaps, the initial resuscitative drugs, there
      is a greater challenge of maintaining that heartbeat for at least the next 24
      hours, which can better ensure a high likelihood of the patient being discharged
      alive from the hospital. A bundle of procedures, which may need to be
      administered simultaneously, is required. These include prompt identification and
      treatment of the cause of cardiac arrest, with early consideration for procedures
      such as percutaneous coronary interventions and fibrinolytics, and treatment of
      electrolyte abnormalities. In addition, a definitive airway and normocapnoeic
      ventilation without causing hyperoxaemia, together with rational management of
      haemodynamics with intra-arterial and central venous lines and vasoactive agents
      will be crucial. Additional benefit is possible with appropriate forms of early
      goal-directed therapy and achieving therapeutic hypothermia within the first few
      hours, followed by gradual rewarming and ensuring glycaemic control by
      maintaining blood sugars within a range of 6-10 mmol /L. All these would be
      important and need to be continued for at least 24 hours, together with a series
      of measures to control neurological reactions and monitor neurological responses
      for best effect. Creation of a bundle that incorporates these various aspects of
      care would more likely ensure that most patients who achieve return of
      spontaneous circulation may be discharged alive from the hospital with optimal
      neurological function.

PMID- 21879222
TI  - The role of nurses in the resuscitation of in-hospital cardiac arrests.
AB  - Survival rates for in-hospital cardiac arrests are disappointing. Even though
      such arrests are often witnessed by a nurse, inadequate training may cause these
      first responders to have to wait for Advanced Cardiac Life Support trained
      personnel to arrive to perform defibrillation. The introduction of automated
      external defibrillator (AED) use by nurses was designed to address this problem,
      but studies have revealed that AED use is associated with a lower rate of
      survival after in-hospital cardiac arrest compared with no AED use. Interruption
      to cardiopulmonary resuscitation during the AED advisory mode is the likely
      reason for these unexpected results. Hence, courses like the Life Support Course
      for Nurses, which trains nurses to recognise collapse rhythms and to institute
      manual defibrillation, are extremely important. Barriers to the practice of
      advanced life support by nurses and recommendations for the prevention and
      management of in-hospital cardiac arrest are discussed.

PMID- 21879223
TI  - Quality of resuscitation in hospitals.
AB  - There is relatively less literature available on in-hospital cardiac arrest
      (IHCA) as opposed to that of out-of-hospital cardiac arrest (OHCA). Although IHCA
      and OHCA patients may differ at baseline, they share similar factors that are
      associated with survival. Important variables need to be standardised for
      reporting. Principles such as the 'chain of survival' remain applicable in the
      response. Early escalation protocols and medical emergency teams, together with
      streamlined activation pathways and staff training, are crucial. Post
      resuscitation care bundles should be implemented.

PMID- 21879224
TI  - Brain attack: needing resuscitation.
AB  - The brain is extremely susceptible to focal ischaemia. Following vascular
      occlusion, a core of severely damaged brain tissue develops, surrounded by an
      ischaemic penumbra. This potentially-salvageable penumbra may be estimated by
      advanced neuroimaging techniques, particularly by diffusion-perfusion mismatch.
      Clinical trials have demonstrated the efficacy of intravenous thrombolysis within
      three hours of onset of ischaemic stroke in reducing short-term disability.
      Recanalisation is enhanced by intra-arterial thrombolysis, sonothrombolysis and
      clot-retrieval devices. Occasionally, reperfusion injury may lead to clinical
      deterioration. The search continues for effective neuroprotectants. Brain
      perfusion needs to be maintained through blood and intracranial pressure
      management. Hemicraniectomy for 'malignant' cerebral oedema reduces death and
      disability. Elevated glucose should be controlled and hypoxia alleviated. Public
      education of symptoms and the need for immediate presentation to a medical
      facility is needed. Stroke unit care reduces death and disability with little
      increase in cost. Current evidence supports urgent efforts to resuscitate the
      brain after stroke.

PMID- 21879225
TI  - Proposal for establishment of a National Sudden Cardiac Arrest registry.
AB  - There is a need to establish a National Sudden Cardiac Arrest registry that would
      track the performance and outcomes of out-of-hospital (OHCA) and in-hospital
      cardiac arrests (IHCA) in the country. An effective strategy to improve survival
      from sudden cardiac arrest in Singapore requires a multi-pronged effort targeting
      the community, Emergency Medical Services (EMS) and the hospitals. The
      establishment of such a registry is important, as it would enable the tracking of
      trends and effectiveness of subsequent interventions related to our national
      strategy for management of both OHCA and IHCA. The quality improvement process of
      measurement-benchmarking-feedback/change is well established. A key part of this
      process is data collection. A cardiac arrest registry can be a key tool for
      quality improvement and serves as an important foundation on which to implement
      and track planned improvements to cardiac arrest management both in and out of
      hospital. It would also aid in planning for deployment of resources,
      interventions and ongoing efforts to improve Singapore's EMS.

PMID- 21879226
TI  - Developing resuscitation programmes in the community: the tasks ahead for the
      National Resuscitation Council.
AB  - Singapore has a long way to go to becoming a 'heartsafe' society. Given our small
      size and culture of hard work in our country, we can achieve a state of good
      first response by our community citizens through public cardiopulmonary
      resuscitation and automated external defibrillators training programmes at
      various key sectors and through the implementation of public access
      defibrillation in a committed manner. For our second-line responders, investing
      in technology to improve response times and quality of chest compressions with
      earlier interventions will go a long way toward strengthening the chain of
      survival in the community. Building on this strong foundation and having a strong
      hospital-based cardiac arrest management system will ensure that those who
      achieve return of spontaneous circulation will more likely remain alive and be
      discharged from hospital in a neurologically optimal state.

PMID- 21879227
TI  - Medico-legal issues in cardiopulmonary resuscitation and defibrillation.

PMID- 21879228
TI  - Comment on: "Foreign bodies in the urinary bladder and their management: a
      Pakistani experience".

PMID- 21879231
TI  - Inter-rater reliability of the early functional abilities scale.
AB  - OBJECTIVE: To investigate the inter-rater reliability of the Early Functional
      Abilities (EFA) scale. DESIGN: An observational study of inter-rater reliability
      in an open cohort. PATIENTS: Twenty-four patients with traumatic brain injury in
      need of medical or surgical intervention in the early rehabilitation section of
      the intensive care unit. METHODS: The EFA was assessed by 4 different professions
      in the rehabilitation team. Inter-rater reliability was assessed using linear
      weighted kappa statistics. RESULTS: The overall weighted kappa values of the
      different EFA items varied from 0.27 to 0.60. The items in the sensorimotor
      functional area had the highest pairwise agreement,with a mean kappa range of
      0.68-0.76. The vegetativest ability, position tolerance and wakefulness items had
      the lowest mean kappa values (0.49, 0.33 and 0.49, respectively). Agreement was
      good to excellent between the occupational therapist and physiotherapist across
      the majority of the items, whereas the physician and nurse agreed less with one
      another. CONCLUSION: The inter-rater reliability of the EFA scale was good for
      most items among all the raters. The scale maybe used by all members of the
      interdisciplinary team after training in administration and scoring. A reduction
      in the number of items in the vegetative functional domain is recommended.

PMID- 21879232
TI  - Rasch analysis of the Nottingham extended activities of daily living scale.
AB  - BACKGROUND AND PURPOSE: The Nottingham Extended Activities of Daily Living (EADL)
      Scale is frequently used in clinical practice and research in rehabilitation to
      assess patients' independence in activities of daily living. Summative scores are
      used for this purpose, but this is problematic because the EADL is an ordinal
      level measurement scale. OBJECTIVES: To examine the fit of data to the Rasch
      model and to determine how the fit could be improved by making changes to the
      scale. The appropriateness of using total and subscale (Mobility, Kitchen,
      Domestic and Leisure) scores in determining change over time was evaluated.
      METHODS: EADL data (n = 210 stroke patients, 55% male, age range 27-93 years)
      from a randomized trial of a Stroke family support organiser service were
      analysed using the Partial Credit model. RESULTS: Rasch analysis did not support
      the total scale as a unidimensional measure of activities of daily living.
      However,the subscales exhibited reasonable fit to the Rasch model following re
      scoring and removal of items. Item 16 exhibited differential item functioning for
      age and item 22 differential item functioning for gender. CONCLUSION: The results
      endorse the use and psychometric properties of the 4 EADL subscales, but not the
      total scale.Further work to corroborate these findings would be useful.

PMID- 21879233
TI  - Progressive muscle relaxation therapy for atopic dermatitis: objective assessment
      of efficacy.
AB  - The aims of this study were to validate the efficacy of progressive muscle
      relaxation (PMR) in patients with atopic dermatitis and to evaluate the
      serological parameters that may serve as objective measures of the efficacy of
      PMR. A total of 25 patients with atopic dermatitis were randomly assigned to
      either a PMR group (n = 15) or a control group (n = 10). Serum levels of nerve
      growth, neuropeptide Y, and Th2 cytokines (IL-4, IL-5, and IL-13) were measured
      at baseline and after one month. At baseline, only anxiety was positively
      correlated with pruritus score (state anxiety: R = 0.496, p = 0.014; trait
      anxiety: R = 0.423, p = 0.04). Serum levels of neuropeptide Y were inversely
      related to the State-Trait Anxiety Inventory (STAI) (state anxiety: R = -0.475, p
      = 0.019; trait anxiety: R = -0.418, p = 0.042) and pruritus scores (R = -0.451, p
      = 0.035). After one month of PMR therapy, the degree of pruritus and loss of
      sleep was significantly decreased in the PMR group (p < 0.001), but not among
      controls. State anxiety scores showed significant improvement after treatment
      only in the PMR group (p = 0.005). There were no significant changes in the
      serological parameters in either group. Reductions in Eczema Area and Severity
      Index (EASI) scores were significant, but similar, in both groups. PMR may be a
      useful adjunctive modality for the management of atopic dermatitis through the
      reduction of anxiety. No change was found in biological parameters, but it was
      observed that neuropeptide Y may be related to high levels of anxiety in atopic
      dermatitis at baseline.

PMID- 21879234
TI  - Polymorphisms in the ATG16L1 gene are associated with psoriasis vulgaris.

PMID- 21879235
TI  - Mast cells as regulators of skin inflammation and immunity.
AB  - Mast cells are known to be the effector cells of immediate-type allergy, but
      experimental evidence obtained during the last decade has revealed their role in
      innate and acquired immunity. Upon activation mast cells can undergo an
      anaphylactic or piecemeal degranulation or degranulation-independent mediator
      secretion, resulting in rapid or slow release of soluble mediators, such as
      serine proteinases, histamine, lipid-derived mediators, cytokines, chemokines and
      growth factors. Mast cells can express different receptors and ligands on the
      cell surface, molecules that can activate the cells of the immune system, such as
      different subsets of T cells. All these mediators and cell surface molecules can
      promote inflammation in the skin. During the last years, a new role for mast
      cells has emerged; induction of tolerance or immunosuppression and interaction
      with regulatory T cells. However, the mechanisms that switch the proinflammatory
      function of mast cells to an immunosuppressive one are unknown. In this review,
      the immunoregulatory function of mast cells and its relation to skin inflammation
      are discussed.

PMID- 21879236
TI  - Sequential occurrence of pemphigus vulgaris and palmoplantar pustulosis: possible
      role of cytokine profile.

PMID- 21879237
TI  - Genotype-phenotype correlation in Chinese patients with dystrophic epidermolysis
      bullosa pruriginosa.
AB  - Dystrophic epidermolysis bullosa pruriginosa (DEB-Pr) is a rare variant of
      dystrophic epidermolysis bullosa (DEB) due to dominant or recessive mutations in
      the COL7A1 gene. More than 40 mutations in COL7A1 have been described in DEB-Pr.
      The aim of this study was to understand the genotype-phenotype correlation in
      Chinese patients with DEB-Pr. Three Chinese families with typical clinical
      features of DEB-Pr were studied. The results were analysed in association with
      the eight Chinese DEB-Pr patients reported in the literature. In the three
      Chinese families with DEB-Pr, we found two dominant cases with G1773R and
      c.6900+1G>C mutations, and one case with heterozygous G2701W mutation of
      uncertain inheritance mode. In the 10 Chinese patients with dominant type of DEB
      Pr, 7 glycine substitutions and three splicing site mutations of exon 87 skipping
      were identified. Glycine substitution mutations in the triple helix region and
      exon 87 skipping, leading to the in-frame deletion of 23 amino acid residues in
      the triple-helix, are often seen in Chinese patients with dominant DEB-Pr,
      although the glycine substitutions are also frequently present in dominant DEB.

PMID- 21879238
TI  - Disseminated BCG infection in severe combined immunodeficiency.

PMID- 21879239
TI  - Rapid progression of hidradenitis suppurativa in the lower leg of a patient with
      psoriasis vulgaris.

PMID- 21879240
TI  - Characterization of peripheral natural killer cells and their reduction in drug
      induced hyper-sensitivity syndrome.

PMID- 21879241
TI  - Metachronous Merkel cell carcinoma on both cheeks.
AB  - Merkel cell carcinoma (MCC), an aggressive skin cancer with neuroendocrine
      features, has been found to be associated with a new type of human polyomavirus
      called Merkel cell polyomavirus (MCV). Patients diagnosed with MCC have a
      significantly increased risk of a second primary cancer. We report here the first
      case of two primary MCCs arising on the face at different times, associated with
      MCV infection. The tumour on the patient's right cheek was surgically removed,
      followed by chemoradiation. After a 10-year tumour-free period, a new tumour
      developed on the patient's left cheek. Histological and immunohistochemical
      findings were consistent with MCC. The tumours had high MCV copy numbers and
      expressed large T antigen, which may play a major role in MCV-mediated
      carcinogenesis. This case highlights the close links between MCC and MCV.

PMID- 21879242
TI  - A subungual blue naevus showing expansile growth.

PMID- 21879243
TI  - Patients with psoriasis feel stigmatized.
AB  - Stigmatization is defined as having a discrediting mark that leads to social
      discrimination and alienation. The aim of this study was to estimate the level of
      stigmatization experienced by patients with psoriasis. A total of 102 individuals
      with psoriasis were recruited and was assessed using the 6-item Stigmatization
      Scale and the 33-item Feelings of Stigmatization Questionnaire. In addition,
      quality of life, stress and depression were evaluated. The majority of patients
      felt that they were stigmatized by psoriasis. The most bothersome aspect was that
      other people stared at their skin changes. According to the 33-item
      questionnaire, anticipation of rejection and feelings of guilt and shame were the
      major aspects of stigmatization, the level of which correlated significantly with
      pruritus intensity, stress prior to exacerbation, depressive symptoms and quality
      of life. In order to decrease the stigmatization level in patients with
      psoriasis, greater effort is needed to raise awareness in contemporary societies
      that psoriasis is not contagious, but is a disease like many other chronic
      conditions.

PMID- 21879244
TI  - An unusual missense mutation in the GJB3 gene resulting in severe
      erythrokeratodermia variabilis.

PMID- 21879245
TI  - Prevalence, correlates and characteristics of chronic pruritus: a population
      based cross-sectional study.
AB  - Pruritus is the most frequent symptom in dermatology. Its impact on quality of
      life is substantial. Epidemiological data on chronic pruritus (>6 weeks) at the
      population level is sparse, but is important in order to understand the burden
      and risk factors of this distressing symptom. The aim of this population-based
      cross-sectional study was to estimate the point, 12-month and lifetime prevalence
      of chronic pruritus, assessing its association with sociodemographic variables
      and describing its characteristics. A validated postal questionnaire was sent to
      4,500 individuals in from the German General population. Three contact attempts
      were made. The response rate was 57.8% (n=2,540). The point prevalence of chronic
      pruritus was 13.5% (95% confidence interval (95% CI) 12.2-14.9%), 12-month
      prevalence 16.4% (15.0-17.9%) and lifetime prevalence 22.0% (20.4-23.7%).
      Multivariate analyses found only ethnic origin independently associated with
      chronic pruritus. The impact of chronic pruritus on quality of life and emotional
      well-being appears to depend on severity rather than on the presence of the
      symptom alone. This is the first study to investigate various prevalence
      estimates of chronic pruritus at the population level. Despite its limitations
      (self-report and potential self-selection) this study indicates a high burden of
      chronic pruritus in society.

PMID- 21879246
TI  - Serum CXCL13 chemokine is not a marker for active Lyme borreliosis.

PMID- 21879247
TI  - Lactase deficiency: a potential novel aetiological factor in chronic pruritus of
      unknown origin.
AB  - Chronic pruritus, which is associated with a wide variety of underlying diseases,
      represents a challenge in diagnostics and treatment in dermatology and general
      medicine. The cause of pruritus remains unknown in up to 45% of patients. In this
      study, 718 patients with chronic pruritus were analysed concerning lactase
      deficiency, demographic data, aetiology, duration and intensity of pruritus. A
      total of 154 patients were tested positive for lactase deficiency and 38.3%
      showed a significant anti-pruritic response to a lactose-free diet (minimum 4
      weeks). The best results were observed in patients with pruritus of mixed or
      unknown origin (n = 91; 64% response). Age, sex, localization or duration had no
      significant influence on the anti-pruritic effect of a lactose-free diet. Lactase
      deficiency might be an independent causal factor in the elicitation of chronic
      pruritus. Thus, screening for lactase deficiency represents a rational step in
      the diagnostic work-up of chronic pruritus. In case of a positive test result, a
      lactose-free diet offers a low-cost, efficient and specific therapy in patients
      with chronic pruritus.

PMID- 21879248
TI  - Co-culture of melanocytes with adipose-derived stem cells as a potential
      substitute for co-culture with keratinocytes.
AB  - Cell-to-cell interactions between melanocytes and keratinocytes increase the
      proliferation and migration of melanocytes. In fact, mixed keratinocyte and
      melanocyte cultures have been used for autologous cell transplantation for
      treatment of vitiligo. However, this may require taking an amount of skin tissue
      large enough to leave scars. In this study, the in vitro effect of adipose
      derived stem cells (ADSCs) on proliferation, differentiation and migration of
      melanocytes was compared with that of keratinocytes using immunohistochemistry
      and a Boyden chamber migration assay. The proliferation and migration of
      melanocytes was significantly stimulated by co-culture with ADSCs compared with
      melanocyte monocultures, al-though the effect of ADSCs was less powerful than
      that of keratinocytes. This may be related to increases in stem cell factor and
      basic fibroblast growth factor, growth factors for melanocytes, produced by the
      ADSCs. The ratios of melanocytes stained with antibodies against Trp-2, E
      cadherin and N-cadherin were significantly increased by co-culturing with ADSCs
      compared with co-culturing with keratinocytes as well as melanocyte monocultures.
      The proportion of less-pigmented melanocytes was also increased and sustained for
      a longer duration in the presence of ADSCs. Our data show that co-culturing with
      ADSCs results in increased melanocyte proliferation and migration while reducing
      differentiation, and could provide a means to treat disorders such as vitiligo.

PMID- 21879249
TI  - Oral lesion in leprosy: borderline tuberculoid diagnosis based on detection of
      Mycobacterium leprae DNA by qPCR.
AB  - Oral lesions are rarely reported in paucibacillary forms of leprosy. We report
      here a case with an erythematous hyposensitive lesion in the palate and no skin
      lesions. In addition to routine tests, biopsies of the lesion in the palate and
      of clinically normal surrounding areas were performed and subjected to real-time
      PCR for detection of Mycobacterium leprae DNA. The biopsy of the oral lesion was
      positive for bacilli DNA, followed by positive serum anti-PGL-1 and Mitsuda test,
      but with negative histopathology. The patient was diagnosed with a borderline
      tuberculoid form. After multidrug therapy the lesion had significantly regressed
      and the bacilli DNA detection in the former lesion was negative. The bacilli DNA
      detection in an oral lesion by real-time PCR not only improved leprosy diagnosis,
      but also helped in the classification of clinical form, and in the establishment
      of the appropriate therapeutic regime.

PMID- 21879250
TI  - Teledermatological monitoring of psoriasis patients on biologic therapy.
AB  - Patients with psoriasis who are being treated with biologics require intensive
      monitoring. However, the monitoring tool teledermatology is not commonly used. We
      investigated the applicability of a mobile phone based teledermatological system
      for monitoring psoriasis patients on biologic therapy. Nineteen patients were
      given mobile phones with built-in cameras, in order to transmit health status
      data and images (mobile visits) weekly for a 6-month period. Face-to-face visits
      were carried out at weeks 0, 4, 12 and 24. Image quality, the Psoriasis Area and
      Severity Index (PASI), the handling of adverse events, and patients' feedback
      questionnaires were evaluated. Ninety-five percent of the images were of
      sufficient quality to enable accurate assessment of the PASI. The distance
      between the interpolated face-to-face PASIs and the corresponding mobile visit
      PASIs was 0.46 +/- 2.15 (median +/- interquartile range). All 155 adverse events
      were handled correctly by the system. This teledermatological system represents a
      reliable tool for management of psoriasis patients who are on systemic treatment.

PMID- 21879251
TI  - Bosentan is effective against digital ulcerations and hyperkeratosis in systemic
      sclerosis.

PMID- 21879252
TI  - The potential of mouse skin-derived precursors to differentiate into mesenchymal
      and neural lineages and their application to osteogenic induction in vivo.
AB  - Although previous studies indicate that skin-derived precursors (SKPs) are
      multipotent dermal precursors that share similarities with neural crest stem
      cells (NCSCs), a shared ability for multilineage differentiation toward neural
      crest lineages between SKPs and NCSCs has not been fully demonstrated. Here, we
      report the derivation of SKPs from adult mouse skin and their directed
      multilineage differentiation toward neural crest lineages. Under controlled in
      vitro conditions, mouse SKPs were propagated and directed toward peripheral
      nervous system lineages such as peripheral neurons and Schwann cells, and
      mesenchymal lineages, such as osteogenic, chondrogenic, adipogenic, and smooth
      muscle cells. To ask if SKPs could generate these same lineages in vivo, a
      mixture of SKP-derived mesenchymal stem cells and hydroxyapatite/tricalcium
      phosphate was transplanted into the rat calvarial defects. Over the ensuing 4
      weeks, we observed formation of osteogenic structure in the calvarial defect
      without any evidence of teratomas. These findings demonstrate the multipotency of
      adult mouse SKPs to differentiate into neural crest lineages. In addition, SKP
      derived mesenchymal stem cells represent an accessible, potentially autologous
      source of precursor cells for tissue-engineered bone repair.

PMID- 21879253
TI  - Response to low-dose X-irradiation is p53-dependent in a papillary thyroid
      carcinoma model system.
AB  - The link between high doses of radiation and thyroid cancer has been well
      established in various studies, as opposed to the effects of low doses. In this
      study, we investi-gated the effects of low-dose X-ray irradiation in a papillary
      thyroid carcinoma model with wild-type and mutated p53. A low dose of 62.5 mGy
      was enough to cause an upregulation of p16 and a decrease in the number of TPC-1
      cells in the S phase, but not in the number of BCPAP p53-mutant cells. At a dose
      of 0.5 Gy, visible signs of senescence appeared only in the TPC-1 cells. We
      conclude that low doses of X-rays are enough to cause a change in cell cycle
      distribution, possibly p53-dependent p16 activation, but no significant
      apoptosis. Senescence requires higher doses of X-irradiation via a mechanism
      involving both p16 and p21.

PMID- 21879254
TI  - Altered intestinal epithelium-associated lymphocyte repertoires and function in
      ApcMin/+ mice.
AB  - ApcMin/+ mice spontaneously develop multiple intestinal adenomas along the length
      of the small intestine and colon. Currently little is known about the role of the
      immune system in regulating intestinal tumorigenesis in these animals. This study
      characterised small intestinal intraepithelial lympho-- cyte (IEL) populations in
      C56BL/6J ApcMin/+ mice and wild-type (Apc+/+) mice. We also determined the effect
      that T cells expressing either gammadelta or alphabeta encoded T cell receptors
      (TcR) exert on intestinal tumorigenesis. ApcMin/+ mice had significantly lower
      numbers of CD3+ IELs compared with Apc+/+ littermates and displayed reduced
      cytotoxicity against tumour target cells. Further analysis of IEL cytotoxicity
      revealed differences in the cytotoxic pathways utilised by IELs in ApcMin/+ and
      Apc+/+ mice with ApcMin/+ IELs displaying an absence of perforin/granzyme
      mediated killing and increased levels of Fas-FasL-mediated cytotoxicity compared
      with wild-type IELs. Analysis of ApcMin/+ mice crossed with alphabeta T-cell
      deficient (TcRbeta-/-) or gammadelta T-cell deficient (TcRdelta-/-) mice on the
      same genetic background revealed decreased tumour multiplicity in the absence of
      both alphabeta and gammadelta T-cells. This study demonstrates that altered T
      cell subsets play important roles in promoting tumorigenesis in ApcMin/+ mice and
      forms the basis for future mechanistic studies.

PMID- 21879255
TI  - The effect of a dimeric Affibody molecule (ZEGFR:1907)2 targeting EGFR in
      combination with radiation in colon cancer cell lines.
AB  - The epidermal growth factor receptor (EGFR) is frequently overexpressed in
      colorectal cancer and is therefore an attractive target for treatment.
      (ZEGFR:1907)2 is a newly developed dimeric affibody molecule with high affinity
      to the extracellular part of EGFR. In this study, we evaluated the cytotoxic
      effects of (ZEGFR:1907)2 in combination with external radiation and the possible
      inhibitory effects in the EGFR signalling pathways in the colon cancer cell lines
      HT-29 and HCT116. The effects were compared with an EGFR antibody (cetuximab) and
      the tyrosine kinase inhibitors (erlotinib and sunitinib). These cell lines are
      genotypically different with respect to e.g. KRAS and BRAF mutational status,
      recently shown to be of clinical significance for therapeutic effects. Both cell
      lines express approximately 100,000-150,000 EGFRs per cell but differ in the
      radiation response (HCT116, SF2=0.28 and HT-29, SF2=0.70). Exposure to
      (ZEGFR:1907)2 produced a small, but significant, reduction in survival in HCT116
      but did not affect HT-29 cells. Similar results were obtained after exposure to
      EGF and the EGFR antibody cetuximab. The EGFR tyrosine kinase targeting inhibitor
      erlotinib and the multi-tyrosine kinase inhibitor sunitinib reduced survival in
      both cell lines. However, none of the drugs had any significant radiosensitizing
      effects in combination with radiation. Akt and Erk are central proteins in the
      EGFR downstream signalling and in the cellular response to ionizing radiation.
      The activation of Akt (Ser 473) and Erk (Thr202/Tyr204) by radiation was both
      dose- and time-dependent. However the activation of EGFR was not clearly affected
      by radiation. Neither (ZEGFR:1907)2 nor any of the other drugs were able to
      completely inactivate Akt or Erk. On the contrary, erlotinib stimulated Akt
      phosphorylation in both cell lines and in HCT116 cells Erk was activated. Overall
      the results illustrate the complexity in response to radiation and drugs in cells
      with differential phenotypic status.

PMID- 21879256
TI  - State of heat shock factor 1 expression as a putative diagnostic marker for oral
      squamous cell carcinoma.
AB  - Heat shock factor 1 (HSF1) is responsible for expres-- sion of a large class of
      heat shock proteins that have been implicated in the malignant phenotype of human
      cancers. Little is known about the effect of a high level of HSF1 on the behavior
      of oral squamous cell carcinoma (OSCC). In this study, we assessed the value of
      HSF1 for predicting clinical outcomes in OSCC. Quantitative reverse transcriptase
      polymerase chain reaction and Western blotting showed that the expressions of
      HSF1 mRNA and protein in OSCC-derived cell lines (HSC-2, HSC-3, HSC-4, Sa3, Ca9
      22, KON and Ho-1-u-1) were elevated compared with those in human normal oral
      keratinocytes (P<0.05). Similar to in vitro data, HSF1 mRNA expression in primary
      OSCCs (n=50) was significantly greater than in normal counterparts (P<0.05).
      Since HSF1 was observed in the nucleus and cytoplasm by immu-- nohistochemistry,
      we investigated the correlation between the HSF1 expression status at each
      subcellular location and the clinical behavior of OSCCs. Among the clinical
      classifications, higher nuclear HSF1 expression was closely related to tumor size
      and histopathologic types (P<0.05). These results showed for the first time that
      nuclear HSF1 expression may contribute to cancer progression and that HSF1 might
      be a potential diagnostic biomarker and a therapeutic target for OSCCs.

PMID- 21879257
TI  - MicroRNA-125b-2 confers human glioblastoma stem cells resistance to temozolomide
      through the mitochondrial pathway of apoptosis.
AB  - MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate protein
      expression by cleaving or repressing the translation of target mRNAs. miR-125b,
      one of the neuronal miRNAs, was recently found to be necessary for stem cell
      fission and for making stem cells insensitive to chemotherapy signals.
      Temozolomide (TMZ) is a promising chemotherapeutic agent for treating
      glioblastomas. However, resistance develops quickly and with a high frequency.
      Given the insensitivity of some glioblastomas to TMZ and the hypothesis that
      glioma stem cells cause resistance to drug therapy, exploring the functions and
      mechanisms of miR-125b action on TMZ-treated glioblastoma stem cells would be
      valuable. In this study, we found that miR-125b-2 is overexpressed in
      glioblastoma multiforme tissues and the corresponding stem cells (GBMSC);
      downregulation of miR-125b-2 expression in GBMSC could allow TMZ to induce GBMSC
      apoptosis. Additionally, the expression of the anti-apoptotic protein Bcl-2 was
      decreased after the TMZ+miR-125b-2 inhibitor treatment, while the expression of
      the proapoptotic protein Bax was increased. Further research demonstrated that
      the induction of apoptosis in GBMSC is also associated with increased cytochrome
      c release from mitochondria, induction of Apaf-1, activation of caspase-3 and
      poly-ADP-ribose polymerase (PARP). Taken together, these results suggest that miR
      125b-2 overexpression might confer glioblastoma stem cells resistance to TMZ.

PMID- 21879258
TI  - Dickkopf-3 maintains the PANC-1 human pancreatic tumor cells in a
      dedifferentiated state.
AB  - Pancreatic cancer (PaCa) is the fourth leading cause of cancer deaths in Western
      societies, with pancreatic ductal adenocarcinomas (PDACs) accounting for >90% of
      such cases. PDAC is a heterogeneous disease that includes a subset showing
      overexpression of the secreted glycoprotein Dickkopf-related protein 3 (Dkk-3), a
      protein shown to be downregulated in various cancers of different tissues. The
      biological function of Dkk-3 in this subset was studied using the Dkk-3
      expressing PANC-1 cell line as a model for PDACs. The influence of Dkk-3
      overexpression and knockdown on cellular differentiation and proliferation of
      PANC-1 was investigated. Confocal microscopy showed that Dkk-3 was expressed in a
      fraction of PANC-1 cells. While lentiviral-mediated overexpression of DKK3 did
      not alter cellular proliferation, knockdown of DKK3 resulted in significant
      reduction of cellular proliferation and concomitant induction of cell cycle
      inhibitors CDKN2B (p15INK4b), CDKN1A (p21CIP1) and CDKN1B (p27KIP1). In parallel,
      pancreatic epithelial cell differentiation markers AMY2A, CELA1, CTRB1, GCG, GLB1
      and INS were significantly upregulated. PANC-1 cells differentiated using exendin
      4 showed analogous induction of cell cycle inhibitors and differentiation
      markers. Thus, we conclude that Dkk-3 is required to maintain a highly
      dedifferentiated and consequently proliferative state in PANC-1, indicating a
      similar function in the Dkk-3 overexpressing subset of PDACs. Therefore, Dkk-3
      represents a potential target for the treatment of Dkk-3-positive subtypes of
      PaCa to drive cells into cell cycle arrest and differentiation.

PMID- 21879259
TI  - Effect of human cytomegalovirus infection on the expression of Hoxb2 and Hoxb4
      genes in the developmental process of cord blood erythroid progenitors.
AB  - The aim of the present study was to investigate the role of Hoxb2 and Hoxb4 gene
      expression induced by human cytomegalovirus (HCMV) and/or all-trans retinoic acid
      (ATRA) on the proliferation and committed differentiation process of human cord
      blood hematopoietic stem cells (HSCs) to colony-forming erythroid progenitor
      cells (CFU-Es) in vitro. Cord blood was collected from the fetal placenta
      umbilical vein in 12 cases and cultured using hematopoietic stem cell culture
      technique in vitro. The proliferation and differentiation of cord blood HSCs to
      CFU-Es were continuously disrupted with HCMV-AD169 and/or 6 x 10-8 mol/l of ATRA.
      Expression levels of the Hoxb2 and Hoxb4 genes in the blank, ATRA, HCMV-AD169 and
      ATRA + HCMV treatment groups of CFU-Es were detected on day 3, 7 and 10 of
      culture by fluorescent quantitative reverse transcriptase-polymerase chain
      reaction method. Hoxb2 and Hoxb4 gene expression in each group began on day 3,
      obviously increased on day 7 and reached a peak on day 10. The expression levels
      of the Hoxb2 and Hoxb4 genes in the HCMV group were obviously down-regulated
      compared with the level in the blank group. However, expression levels of the
      Hoxb2 and Hoxb4 genes were significantly up-regulated in the HCMV + ATRA group
      compared with the HCMV group (P<0.05). Abnormal expression of the Hoxb2 and Hoxb4
      genes induced by HCMV may play important roles in abnormal hematopoietic damage.
      They were also correlated with the process of erythroid hematopoiesis. ATRA (6 x
      10-8 mol/l) significantly up-regulated expression of the Hoxb2 and Hoxb4 genes in
      the normal erythroid progenitor cells and in those cells infected with HCMV as
      well.

PMID- 21879260
TI  - Inhibition of cell motility and invasion by HangAmDan-B in NCI-H460 human non
      small cell lung cancer cells.
AB  - Correlation between inhibition of cell motility and anti-invasive activity by the
      water extract of HangAmDan-B (HAD-B), a crude extract of eight Korean medicinal
      animals and plants, in NCI-H460 human non-small cell lung cancer (NSCLC) cells
      was investigated. Within the concentrations that were not cytotoxic, HAD-B
      induced significant concentration-dependent inhibition of cell motility and
      invasiveness of NCI-H460 cells. Treatment with HAD-B resulted in dose-dependent
      inhibition of the activities of matrix metallo-proteinase (MMP)-2 and MMP-9, and
      this was correlated with a decrease in expression of their mRNA and proteins, and
      upregulation of tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2
      expression. Anti-invasive activity of HAD-B was also found to be associated with
      increased tightness of the tight junction (TJ), as demonstrated by an increase in
      transepithelial electrical resistance. In addition, the present results indicated
      that treatment with HAD-B resulted in repression of the levels of claudin family
      members, which are major components of TJs that play a key role in control and
      selectivity of para-cellular transport. Although further studies are needed,
      findings from the present study indicate that TJs and MMPs are critical targets
      of HAD-B-induced anti-invasiveness in NCI-H460 NSCLC cells.

PMID- 21879261
TI  - A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin
      and 5-fluorouracil versus preoperative chemotherapy for localized advanced
      squamous cell carcinoma of the thoracic esophagus (JCOG9907).
AB  - BACKGROUND: Patients with esophageal carcinoma receiving postoperative
      chemotherapy showed superior disease-free survival than those receiving surgery
      alone in a Japan Clinical Oncology Group trial (JCOG9204). The purpose of this
      study was to evaluate optimal perioperative timing-that is, before or after
      surgery-for providing chemotherapy in patients with locally advanced esophageal
      squamous cell carcinoma. METHODS: Eligible patients with clinical stage II or
      III, excluding T4, squamous cell carcinoma were randomized to undergo surgery
      followed (group 1) or preceded (group 2) by chemotherapy consisting of two
      courses of cisplatin plus 5-fluorouracil. The primary end point was progression
      free survival. RESULTS: We randomized 330 patients, with 166 assigned to group 1
      and 164 to group 2, between May 2000 and May 2006. The planned interim analysis
      was conducted after completion of patient accrual. Progression-free survival did
      not reach the stopping boundary, but overall survival in group 2 was superior to
      that of group 1 (P = 0.01). Therefore, the Data and Safety Monitoring Committee
      recommended early publication. Updated analyses showed the 5-year overall
      survival to be 43% in group 1 and 55% in group 2 (hazard ratio 0.73, 95%
      confidence interval 0.54-0.99, P = 0.04), where the median follow-up of censored
      patients was 61.6 months. Concerning operative morbidity, renal dysfunction after
      surgery in group 2 was slightly higher than in group 1. CONCLUSIONS: Preoperative
      chemotherapy with cisplatin plus 5-fluorouracil can be regarded as standard
      treatment for patients with stage II/III squamous cell carcinoma.

PMID- 21879262
TI  - Patterns of recurrence after ablation of colorectal cancer liver metastases.
AB  - PURPOSE: To determine the local recurrence rate and factors associated with
      recurrence after intraoperative ablation of colorectal cancer liver metastases.
      METHODS: A retrospective analysis of a prospectively maintained database was
      performed for patients who underwent ablation of a hepatic colorectal cancer
      metastasis in the operating room from April 1996 to March 2010. Kaplan-Meier
      survival curves and Cox models were used to determine recurrence rates and assess
      significance. RESULTS: Ablation was performed in 10% (n = 158 patients) of all
      cases during the study period. Seventy-eight percent were performed in
      conjunction with a liver resection. Of the 315 tumors ablated, most tumors were
      <= 1 cm in maximum diameter (53%). Radiofrequency ablation was used to treat most
      of the tumors (70%). Thirty-six tumors (11%) had local recurrence as part of
      their recurrence pattern. Disease recurred in the liver or systemically after 212
      tumors (67%) were ablated. On univariate analysis, tumor size greater than 1 cm
      was associated with a significantly increased risk of local recurrence (hazard
      ratio 2.3, 95% confidence interval 1.2-4.5, P = 0.013). The 2 year ablation zone
      recurrence-free survival was 92% for tumors <= 1 cm compared to 81% for tumors >1
      cm. On multivariate analysis, tumor size of >1 cm, lack of postoperative
      chemotherapy, and use of cryotherapy were significantly associated with a higher
      local recurrence rate. CONCLUSIONS: Intraoperative ablation appears to be highly
      effective treatment for hepatic colorectal tumors <= 1 cm.

PMID- 21879263
TI  - Expression of sodium-iodide symporter and TSH receptor in subclinical metastatic
      lymph nodes of papillary thyroid microcarcinoma.
AB  - BACKGROUND: The clinical significance of the subclinical lymph node (LN)
      metastasis in clinically node-negative (cN0) papillary thyroid microcarcinoma
      (PTMC) has been debated. We investigated the expression of sodium-iodide
      symporter (NIS) and thyroid-stimulating hormone receptor (TSHR) in the
      subclinical metastatic LNs of PTMC, which are crucial prerequisites for the
      response to radioactive iodine treatment. METHODS: Among 149 consecutive patients
      who received total thyroidectomy in conjunction with prophylactic central neck
      dissection for cN0 PTMC from October 2005 to December 2007, 20 who had single
      PTMC and subclinical LN metastasis (cN0, pN1, single PTMC) were included.
      Immunohistochemical staining was performed with anti-human NIS antibody and anti
      human TSHR antibody in 20 primary tumors and 52 metastatic LNs. RESULTS: NIS and
      TSHR expression was detected in 19 (95%) and 18 (90%) of 20 PTMCs, respectively.
      NIS and TSHR expression were also detected in 50 (96.2%) and 39 (75%) of 52
      metastatic LNs, respectively. In 85% of patients, the presence of NIS expression
      in primary PTMCs was concordant with that in corresponding metastatic LNs.
      Intensities of NIS and TSHR expression were diverse. In 6 of 12 cases of multiple
      metastatic LNs, the metastatic LNs showed heterogeneous intensities of NIS
      expression. CONCLUSIONS: The presence of NIS and TSHR expression was observed
      with high frequency in both PTMCs and corresponding subclinical metastatic LNs.
      However, the intensity of NIS and TSHR expression was diverse. Multiple
      metastatic LNs from single primary tumor focus could have heterogeneous intensity
      of NIS expression.

PMID- 21879264
TI  - Presurgical localization of parathyroid adenomas with magnetic resonance imaging
      at 3.0 T: an adjunct method to supplement traditional imaging.
AB  - PURPOSE: To investigate the use of a chemical shift-based water-fat separation
      magnetic resonance imaging (MRI) method, and time-resolved contrast-enhanced MRI
      at 3 T for improved presurgical localization of parathyroid adenomas. METHODS:
      Twenty-five patients with primary hyperparathyroidism were prospectively
      enrolled. Patients underwent MRI, which was reviewed by two experienced
      neuroradiologists who were blinded to Tc-99m sestamibi imaging and operative
      results. RESULTS: Overall, MRI detected 16 adenomas in 25 patients (sensitivity
      64%, positive predictive value 67%), while sestamibi detected 18 of 25 adenomas
      (sensitivity 72%, positive predictive value 90%). Importantly, MRI was able to
      detect adenomas in four (57%) of the seven patients whose disease was missed by
      sestamibi analysis. MRI demonstrated excellent image quality and fat suppression
      by using a chemical shift-based water-fat separation technique. The time-resolved
      MRI was considered to be less helpful, although in some cases it was
      indispensable. CONCLUSIONS: MRI is an excellent adjunct for preoperative
      parathyroid localization. The advent of improved fat suppression techniques in
      the neck, including chemical shift-based water-fat separation, is critical to its
      utility. Although time-resolved MRI was not always helpful, it was crucial in
      certain cases. It may prove to be more useful with the development of faster
      scanning techniques.

PMID- 21879265
TI  - Postoperative complications deteriorate long-term outcome in pancreatic cancer
      patients.
AB  - BACKGROUND: Different tumor-specific prognostic factors have been identified in
      recent years for patients who undergo surgery due to pancreatic head cancer, but
      the results often were inconsistent. Furthermore, the impact of postoperative
      complications on patient long-term survival has not been described. METHODS: The
      long-term outcome of 428 patients who underwent resection of pancreatic head
      cancer at our center during a 17-year period was evaluated. Perioperative
      details, including postoperative complications, as well as the follow-up of all
      patients who left the hospital postoperatively were collected in a prospective
      database. Univariate and multivariate models were used to identify potential
      prognostic factors and to evaluate the impact of postoperative complications on
      long-term survival. RESULTS: The median survival was 15.5 months with a
      postoperative complication rate (grade I-IV) of 32.7%. Independent prognostic
      significance was detected for grading (P < 0.001), R status (P = 0.001), and
      lymph node status (P = 0.003). The occurrence of severe postoperative
      complications (grade III-IV) was associated with a significantly shortened
      survival (16.5 vs. 12.4 months; P = 0.002) and was identified as an independent
      prognostic factor (P = 0.002). CONCLUSIONS: This large study demonstrates that
      severe postoperative complications have a strong impact on the long-term survival
      of patients with pancreatic head cancer comparable to tumor characteristics, such
      as lymph node status, grading, or R status. As a result, the improvement of
      surgical procedures in specialized centers might lead to a survival benefit in
      these patients.

PMID- 21879266
TI  - Increased CD13 expression reduces reactive oxygen species, promoting survival of
      liver cancer stem cells via an epithelial-mesenchymal transition-like phenomenon.
AB  - BACKGROUND: Recently, it has been reported that a small population of cancer stem
      cells (CSCs) play a role in resistance to chemotherapy and radiation therapy. We
      reported that CD13(+) liver CSCs survive in hypoxic lesions after chemotherapy,
      presumably through increased expression of CD13/Aminopeptidase N, which is a
      scavenger enzyme in the reactive oxygen species (ROS) metabolic pathway. On the
      other hand, the concept of epithelial-mesenchymal transition (EMT) was indicated
      by a recent study showing an increased plasticity linked to the cellular
      "stemness" of CSCs. METHODS: To study the relationship between CSCs and EMT, we
      examined biological characteristics of liver cancer cell lines with EMT by
      exposing transforming growth factor-beta (TGF-beta). RESULTS: We showed that a
      TGF-beta-induced EMT-like phenomenon is associated with increased CD13 expression
      in liver cancer cells. This phenomenon prevents further increases in the ROS
      level as well as the induction of apoptosis, promoting the survival of CD13(+)
      CSCs, whereas inhibition of CD13 stimulates apoptosis. Immunohistochemical
      analysis also indicated that after chemotherapy, CD13 was coexpressed with N
      cadherin in surviving cancer cells within fibrous capsules. We have demonstrated
      that CD13 expression plays a role in supporting the survival of CSCs and that
      there is an EMT-associated reduction in ROS elevation. CONCLUSIONS: This novel
      and consistent linkage between functional CSC markers and the EMT phenomenon
      suggests a bona fide candidate for targeted therapy for EMT-mediated invasion and
      metastasis of liver cancer.

PMID- 21879267
TI  - Behavior of serous borderline ovarian tumors with and without micropapillary
      patterns: results of a French multicenter study.
AB  - BACKGROUND: Behavior of serous borderline ovarian tumors with micropapillary
      patterns (MP-SBOT) is thought to be worse than those without micropapillary
      patterns, but few cohort studies have compared epidemiological characteristics,
      surgical management, and recurrence rates between these two groups. METHODS: In a
      French retrospective multicenter study of 475 borderline ovarian tumors (BOT)
      treated from 1990 to 2009, we studied patients with a serous BOT and treated
      after 2000 including 20 patients with and 77 patients without micropapillary
      patterns. RESULTS: Patients with MP-SBOT were younger (P = 0.01), often
      asymptomatic (P = 0.04), and with abnormal CA 125 serum levels (P = 0.04).
      Peritoneal implants were more frequently observed in these patients (P = 0.01);
      also, they underwent conservative treatment more frequently (P = 0.002), had a
      higher risk of misdiagnosis with invasive carcinoma by intraoperative histology
      (P < 0.05), and had more frequent restaging surgery (P = 0.001). No difference in
      recurrence was noted between the groups. No disease-related mortality was
      observed. CONCLUSIONS: Patients with MP-SBOT represent a heterogeneous population
      in terms of presence of invasive peritoneal implants. Conservative surgery could
      be a suitable option for MP-SBOT patients without implants and who wish to
      conserve childbearing potential, without increasing the risk of recurrence.

PMID- 21879268
TI  - Is intraoperative imprint cytology evaluation still feasible for the evaluation
      of sentinel lymph nodes for lobular carcinoma of the breast?
AB  - BACKGROUND: The evaluation of sentinel lymph nodes (SLNs) from a patient with
      lobular breast cancer is challenging. Metastatic lobular cancer is difficult to
      identify in SLNs because of its low-grade cytomorphology and its tendency to
      resemble lymphocytes. Intraoperative imprint cytology (IIC) is a rapid, reliable
      method for evaluating SLNs intraoperatively. We sought to reexamine our
      experience with this technique in the identification of invasive lobular breast
      cancer SLN metastases. METHODS: A retrospective review of a prospectively
      maintained database of IIC results of 1010 SLN mapping procedures for breast
      cancer was performed. From this cohort we reviewed SLN cases of lobular cancer.
      The SLNs were evaluated intraoperatively by bisecting the SLN. Imprints were made
      of each cut surface and stained with hematoxylin and eosin (H&E) and Diff-Quik.
      Permanent sections were evaluated with up to 4 H&E-stained levels and cytokeratin
      immunohistochemistry. IIC results were compared with final pathologic results.
      RESULTS: A total of 67 cases of pure invasive lobular cancer were identified. The
      sensitivity was 71%, specificity was 100%, and accuracy was 92%. No statistically
      significant differences in sensitivity, specificity, or accuracy were identified
      between the intraoperative detection of lobular carcinoma vs ductal carcinoma.
      The specificity has remained the same since 2004. However the accuracy (82% vs
      92%; P = .09) and sensitivity (52% vs 71%; P = .02) has improved since 2004.
      CONCLUSIONS: As we have previously shown, the sensitivity and specificity of IIC
      in evaluating lobular carcinoma is feasible and accurate. IIC continues to be a
      viable alternative to frozen section for intraoperative evaluation.

PMID- 21879270
TI  - Prognostic value of basal phenotype in HER2-overexpressing breast cancer.
AB  - BACKGROUND: Primary breast cancers that overexpress human epidermal growth factor
      receptor 2 have variable biological features and clinical outcomes. A subgroup of
      HER2-overexpressing tumors that express basal-like immunohistochemical markers
      the so-called basal-HER2+ subtype--is associated with poor prognosis. We
      investigated the clinical relevance of this basal-HER2+ subtype within HER2
      overexpressing breast tumors. METHODS: Database review identified consecutive
      patients with HER2-overexpressing breast cancer. Archival tumor specimens from
      these patients were immunostained for estrogen receptor (ER), HER2, and basal
      cytokeratin (CK) expression, then subtyped as luminal-HER2+ (ER positive and
      basal CK negative), HER2+ (ER negative and basal CK negative), and basal-HER2+
      (ER negative and basal CK positive). Subtypes were correlated with
      clinicopathologic features and overall survival. RESULTS: Immunohistochemical
      assessment of 131 HER2-overexpressing breast tumors identified 79 (60%) luminal
      HER2+ tumors, 40 (31%) HER2+ tumors, and 12 (9%) basal-HER2+ tumors. There was no
      difference in the use of adjuvant trastuzumab and chemotherapy among patients
      with these subtypes. Five-year overall survival was 65% for patients with basal
      HER2+ tumors versus 94% (P = 0.0035) and 96% (P = 0.0031) for patients with
      luminal-HER2+ and HER2+ tumors, respectively. The basal-HER2+ subtype was
      associated with the worst prognosis after adjusting for age, tumor size, lymph
      node status, and adjuvant treatment (hazard ratio 5.06, 95% confidence interval
      1.1-23.2, P = 0.037). CONCLUSIONS: The basal-HER2+ subtype highlights the
      heterogeneous biology of HER2-overexpressing breast cancer. The basal-HER2+
      subtype is independently associated with poor survival and may provide insight
      into breast cancer cell response to anti-HER2 therapy.

PMID- 21879269
TI  - Is the 1-cm rule of distal bowel resection margin in rectal cancer based on
      clinical evidence? A systematic review.
AB  - BACKGROUND: Distal intramural spread is present within 1 cm from visible tumor in
      a substantial proportion of patients. Therefore, >= 1 cm of distal bowel
      clearance is recommended as minimally acceptable. However, clinical results are
      contradictory in answering the question of whether this rule is valid. The aim of
      this review was to evaluate whether in patients undergoing anterior resection, a
      distal bowel gross margin of <1 cm jeopardizes oncologic safety. METHODS: A
      systematic review of the literature identified 17 studies showing results in
      relation to margins of approximately <1 cm (948 patients) versus >1 cm (4626
      patients); five studies in relation to a margin of <= 5 mm (173 patients) versus
      >5 mm (1277 patients), and five studies showing results in a margin of <= 2 mm
      (73 patients). In most studies, pre- or postoperative radiation was provided.
      RESULTS: A multifactorial process was identified resulting in selection of
      favorable tumors for anterior resection with the short bowel margin and
      unfavorable tumors for abdominoperineal resection or for anterior resection with
      the long margin. In total, the local recurrence rate was 1.0% higher in the <1-cm
      margin group compared to the >1-cm margin group (95% confidence interval [CI] 
      0.6 to 2.7; P = 0.175). The corresponding figures for <= 5 mm cutoff point were
      1.7% (95% CI -1.9 to 5.3; P = 0.375). The pooled local recurrence rate in
      patients having <= 2 mm margin was 2.7% (95% CI 0 to 6.4). CONCLUSIONS: In the
      selected group of patients, <1 cm margin did not jeopardize oncologic safety.

PMID- 21879271
TI  - The additional value of lymphatic mapping with routine SPECT/CT in unselected
      patients with clinically localized melanoma.
AB  - PURPOSE: To investigate whether single photon emission computed tomography camera
      with integrated radiographic computed tomography (SPECT/CT) is of additional
      value compared to conventional lymphoscintigraphy in routine lymphatic mapping in
      patients with melanoma. METHODS: Thirty-five unselected patients with a primary
      melanoma who were scheduled for wide local excision and sentinel node biopsy
      underwent conventional lymphoscintigraphy and subsequently SPECT/CT. We
      determined whether SPECT/CT showed additional sentinel nodes, whether it provided
      better information on the location of the sentinel nodes, and whether this
      additional anatomic information led to a change in the planned surgical approach.
      RESULTS: SPECT/CT depicted the same 69 sentinel nodes as conventional
      lymphoscintigraphy in all 35 patients plus found eight additional sentinel nodes
      in seven patients (20%). In two of these patients (5.7%), an additional nodal
      basin had to be explored to find the extra sentinel nodes. SPECT/CT provided
      additional anatomic information that was helpful to the surgeon in 11 patients
      (31%) and led to an adjustment of the surgical approach in 10 patients (29%).
      CONCLUSIONS: SPECT/CT provided relevant additional information in 16 (46%) of the
      35 patients. Routine use of SPECT/CT in addition to conventional
      lymphoscintigraphy is recommended in melanoma patients undergoing lymphatic
      mapping.

PMID- 21879272
TI  - 20 years experience of TNF-based isolated limb perfusion for in-transit melanoma
      metastases: TNF dose matters.
AB  - BACKGROUND: Approximately 5-8% of melanoma patients will develop in-transit
      metastases (IT-mets). Tumor necrosis factor-alpha (TNF) and melphalan-based
      isolated limb perfusion (TM-ILP) is an attractive treatment modality in melanoma
      patients with multiple IT-mets. This study reports on a 20 years experience and
      outlines the evolution and major changes since the introduction of TNF in ILP.
      METHODS: A total of 167 TM-ILPs were performed in 148 patients, between 1991 and
      2009. TM-ILPs were performed at high doses of TNF (3-4 mg) from 1991 to 2004 (n =
      99) and at low doses of TNF (1-2 mg) from 2004 to 2009 (n = 68) under mild
      hyperthermic conditions (38 degrees C-39.5 degrees C.). Melphalan doses were
      unchanged at 10-13 mg/l (leg and arm, respectively). Characteristics for the 167
      ILPs were: 81 stage IIIB, 65 stage IIIC, and 21 stage IV disease. RESULTS: The
      overall response rate was 89% (n = 148). (Complete response [CR] = 61%; partial
      response [PR] = 28%). CR rates correlated with stage (P = .001) and with high
      dose vs. low-dose TNF (70% vs. 49%; P < .006). High-dose TNF prolonged local
      control (median 16 months vs. 11 months; P = .076). Survival was not influenced
      by TNF dose. CR after ILP and number of lesions also correlated with local
      progression-free interval. Overall survival did correlate with stage of disease
      (P < .001), size of the lesions (P = .001), and a CR (P < .001). CONCLUSIONS:
      This 2-decade single-center experience demonstrates that TM-ILP is a safe and
      effective treatment modality for melanoma patients with multiple IT-mets. Higher
      dose of TNF was associated with significantly higher CR rates and prolonged local
      control without an effect on overall survival.

PMID- 21879274
TI  - Melanoma in the older patient: measuring frailty as an index of survival.

PMID- 21879273
TI  - Intercellular adhesion molecule-1 (ICAM-1) is upregulated in aggressive papillary
      thyroid carcinoma.
AB  - BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is implicated in
      carcinogenesis. In this study we examined the expression of ICAM-1 in papillary
      thyroid cancer (PTC). We hypothesized that ICAM-1 correlates with indicators of
      tumor aggressiveness in PTC. METHODS: Thirty-five primary and metastatic PTCs,
      five follicular adenomas, five Hashimoto thyroiditis, five nodular hyperplasia,
      and eight normal thyroid tissue samples were analyzed for ICAM-1 gene expression
      using quantitative reverse-transcription polymerase chain reaction (RT-PCR). ICAM
      1 gene expression was analyzed at protein level by immunohistochemistry (IHC)
      using a semiquantitative score. Gene expression and intensity levels were
      correlated with markers of tumor aggressiveness including BRAF V600E mutation,
      tumor size, extrathyroidal extension (ETE), angiolymphatic invasion, and lymph
      node metastasis. RESULTS: ICAM-1 gene expression was higher in PTC (p = 0.01) and
      lymph node metastases (p = 0.03) when compared with benign tumors and
      Hashimoto's. Furthermore, PTCs exhibiting BRAF V600E mutation (p = 0.01), ETE (p
      < 0.01), and lymph node metastasis (p = 0.02) were associated with higher ICAM-1
      levels. Gene expression correlated with protein levels on IHC. Additionally,
      poorly differentiated thyroid carcinoma had a higher ICAM-1 intensity score
      compared with well-differentiated carcinoma (p = 0.03). CONCLUSIONS: ICAM-1
      expression is upregulated in papillary thyroid carcinoma. Furthermore, ICAM-1
      upregulation correlated with aggressive tumor features such as BRAF V600E
      mutation, ETE, and lymph node metastasis, suggesting that ICAM-1 plays a role in
      thyroid cancer progression.

PMID- 21879275
TI  - Screening for Lynch syndrome in colorectal cancer: are we doing enough?
AB  - PURPOSE: The purpose of this study was to assess the efficacy of screening for
      the detection of Lynch syndrome (LS) in an unselected population undergoing
      surgery for a colorectal cancer. METHODS: A total of 1,040 patients were
      prospectively included between 2005 and 2009. LS screening modalities included
      the Bethesda criteria, immunochemistry (IHC) for MLH1, MSH2, and MSH6, and
      microsatellite instability (MSI) by using pentaplex markers. Promoter methylation
      was assessed in tumors with a loss of MLH1 expression. Gene sequencing was
      offered to patients with abnormal IHC or MSI status without promoter methylation.
      RESULTS: A total of 105 patients had an abnormal result: 102 (9.8%) exhibited a
      loss of protein on IHC and 98 (9.4%) had MSI. A discordant result was observed in
      10 patients with eventual proven LS in 6 patients. Loss of MLH1 (n = 64) was due
      to promoter methylation in 43 patients (67.2%). Overall, of 62 patients with an
      abnormal result, 38 had genetic sequencing leading to 25 (65.8%) identified with
      a germ-line mutation. Loss of MSH2 on IHC was associated with a mutation in 78.3%
      (18 of 23) of cases. Among the 62 patients with abnormal results, 23 (37.1%) did
      not meet the Bethesda criteria. CONCLUSIONS: Strict application of the Bethesda
      criteria does not lead to identification of all patients with LS. IHC and MSI
      testing are complementary methods and should be used in association to identify
      potential LS patients.

PMID- 21879276
TI  - Long-term outcomes after resection versus transplantation for hepatocellular
      carcinoma within UCSF criteria.
AB  - PURPOSE: We compared the long-term outcomes of resection and transplantation for
      hepatocellular carcinoma (HCC) while satisfying the University of California at
      San Francisco criteria. METHODS: HCC patients who underwent liver resection (n =
      746) and transplantation (n = 54) between 2001 and 2007 were reviewed. Overall
      and disease-free survival rates were evaluated using the Kaplan-Meier estimator,
      and independent prognostic factors were determined using the Cox proportional
      regression model. The presence of cirrhosis was used to divide the patients into
      groups. The patients who received primary transplantation were further analyzed.
      RESULTS: Nine years after surgery, the patients' overall survival was similar in
      the resection and transplantation groups (75.9 and 77.2%, respectively).
      Furthermore, the recurrence rate in the resection group was higher than that in
      the transplantation group (65 vs. 34.4%; adjusted hazard ratio, 3.27; range, 1.76
      6.08), especially for cirrhosis patients (adjusted hazard ratio, 4.28; range,
      2.14-8.56). The results suggested that noncirrhotic patients who underwent
      resection had a better survival advantage than primary liver transplant
      recipients did (adjusted hazard ratio, 0.46; range, 0.18-1.21). However,
      noncirrhotic patients had higher recurrence rates (59.2 vs. 15.8%; adjusted
      hazard ratio, 3.98; range, 1.26-12.58). Similar trends were noted in patients
      with hepatitis B virus infection and/or a single tumor. CONCLUSIONS: Long-term
      survival rates after liver transplantation and resection were similar, but the
      latter was associated with a higher recurrence rate.

PMID- 21879277
TI  - Different characteristics of thymomas with and without myasthenia gravis.
AB  - BACKGROUND: The objective of this study was to evaluate the different
      pathological and clinical characteristics of thymomas with and without myasthenia
      gravis (MG) and to determine whether the presence of MG influences the prognosis
      in thymoma patients. METHODS: We retrospectively studied data from 228
      consecutive patients operated on from 1992 to 2007 in Beijing Tongren Hospital.
      These thymoma patients have been subdivided into two groups: group A with MG (n =
      125) and group B without MG (n = 103). RESULTS: There were no perioperative
      deaths. There were 19 inoperable cases (6 in the group with MG, 13 without MG, P
      = 0.035). The proportions of types A, AB, B1, B2, B3, and C thymoma in this data
      were 0, 22.4, 26.4, 30.4, 20.8, and 0%, respectively, in the group with MG, and
      10.5, 13.4, 23.6, 24.5, 16.4, and 11.6%, respectively in the group without MG.
      There was a significant difference between hyperplastic paraneoplastic thymus
      coexisting in 28.8% patients with MG and only 5.8% in patients without MG.
      Microthymoma was identified in the paraneoplastic thymus of three patients with
      MG. There were 198 patients followed up. There was no recurrence in patients with
      type A, and a few patients with types AB, B1, B2, B3, and C recurred. The
      actuarial 5- and 10-year survival rates were 89.3 and 81.2% for patients with MG,
      respectively, and 90 and 78.9% for patients without MG, respectively. Within 5
      years postoperatively, 6 of 9 patients with MG died of myasthenia crisis, while 6
      of 7 deaths in patients without MG were attributable to inoperable tumors (stage
      IV) and type C thymoma. CONCLUSIONS: MG seldom occurs in types A and C thymoma.
      MG of some thymoma patients was not caused by thymoma, but by the paraneoplastic
      thymus. The prognosis of thymomas with MG is similar to that without MG. The main
      cause of death is myasthenia crisis for thymoma patients with MG and stage IV
      and/or type C for thymoma patients without MG.

PMID- 21879279
TI  - Twelve-month persistency with oral 5-aminosalicylic acid therapy for ulcerative
      colitis: results from a large pharmacy prescriptions database.
AB  - BACKGROUND: Patients receiving 5-aminosalicylic acid (5-ASA) require long-term
      therapy to achieve good outcomes. Persistency (duration of time from initiation
      to discontinuation of therapy) is therefore an important consideration. AIM: To
      evaluate persistency in patients receiving various oral 5-ASA formulations.
      METHODS: This retrospective, 12-month, cohort study examined new-starter patients
      (any age and diagnosis) from a large United States pharmacy database who filled a
      prescription for oral 5-ASA [Lialda((r)), Asacol((r)), Pentasa((r)) 250 or 500
      mg, balsalazide (generic and Colazal((r))), and olsalazine (Dipentum((r)))]
      between March and September 2007. Persistency was evaluated monthly on the basis
      of prescription refill rates. RESULTS: Prescription and refill records were
      identified for 44,191 patients receiving oral 5-ASA. After 1 year, 20% of
      patients receiving Lialda were considered persistent and classified as continuing
      (refilling within a timeframe of up to twice the duration of the prescription),
      compared with 9% receiving Asacol, 7 (250 mg) and 10% (500 mg) receiving Pentasa,
      10% receiving balsalazide, and 10% receiving Dipentum. CONCLUSIONS: Overall
      persistency with oral 5-ASA therapy was low. However, patients receiving once
      daily Lialda had significantly higher persistency after 1 year of treatment than
      patients receiving other oral 5-ASA therapies.

PMID- 21879280
TI  - Factors affecting the success of endoscopic bougia dilatation of radiation
      induced esophageal stricture.
AB  - AIMS: The purpose of this retrospective study was to assess clinical outcomes of
      endoscopic bougie dilation of esophageal strictures after radiation therapy for
      head and neck cancer, and to assess the risk factors which affect the treatment
      success. METHODS: Thirty-one patients with esophageal stricture due to radiation
      therapy were treated with endoscopic bougie dilation. The following parameters
      were evaluated; age, gender, primary site of the tumor, initial treatment of the
      tumor, prescribed dose of radiation, the time to onset of esophageal stricture
      after radiation therapy, grade of esophageal stricture according to clinical and
      endoscopic findings, number of dilatations, recurrence of esophageal stricture,
      and the result of the therapy. RESULTS: The average follow-up was 26 months with
      a range of 1-84 months. Successful endoscopic bougie dilation was achieved in 26
      of 31 patients. The median time to onset of esophageal stricture after radiation
      therapy was significantly shorter in patients who did not respond to endoscopic
      bougie dilation. CONCLUSION: Endoscopic bougie dilation is a safe and effective
      procedure for the management of radiation-induced esophageal stricture. Time to
      onset of esophageal stricture is the most important factor for the treatment
      success. In addition, the total prescribed dosage of radiation has minimal
      effects on the result of endoscopic bougie dilation.

PMID- 21879281
TI  - Endoscopic management of liver abscess with biliary communication.
AB  - BACKGROUND AND STUDY AIMS: The formation of a communication between liver
      abscesses and intrahepatic bile ducts is an uncommon cause of bile leak. The
      surgical management of biliary fistulas is associated with high morbidity and
      mortality. We performed a prospective study of the endoscopic management of liver
      abscess communicating with bile ducts. PATIENTS AND METHODS: We studied 38
      patients with liver abscesses that had ruptured into the intrahepatic bile ducts.
      The presence of a biliary fistula was suspected by jaundice and/or by the
      appearance of bile in percutaneous drainage effluent from a liver abscess and was
      confirmed by endoscopic retrograde cholangiopancreatography (ERCP). Subsequently,
      patients underwent treatment by endoscopic sphincterotomy and either biliary
      stenting or nasobiliary drainage. Nasobiliary drains or biliary stents (both 7
      Fr) were placed according to standard techniques. Nasobiliary drains were removed
      when bile leakage stopped and closure of the fistula was confirmed by
      cholangiography; stents were removed after an interval of 4-6 weeks. RESULTS: Of
      the total of 586 patients with liver abscesses, seen over a 10-year period, there
      were 38 (30 amebic, 8 pyogenic) patients who developed a biliary fistula between
      the liver abscess cavity and the intrahepatic bile ducts (right intrahepatic bile
      ducts in 30 patients, left intrahepatic bile ducts in 8 patients). We performed
      either endoscopic sphincterotomy with insertion of a nasobiliary drain (n = 18)
      or endoscopic sphincterotomy with biliary stenting (n = 20). The fistulas healed
      in all patients after a median time of 6 days (range 4-40 days) after endoscopic
      treatment. The nasobiliary drainage catheters and stents were removed after 8-40
      days of their placement. CONCLUSIONS: Endoscopic therapy is an effective mode of
      treatment for biliary fistulas complicating liver abscesses.

PMID- 21879282
TI  - Clinical usefulness of endoscopic ultrasonography in the differential diagnosis
      of gallbladder wall thickening.
AB  - BACKGROUND AND AIMS: The differential diagnosis of gallbladder (GB) cancer from
      inflammatory diseases in patients with a thickened GB wall is difficult, whereas
      the pre-operative diagnosis of GB cancer is critical for selecting the
      appropriate surgical modality. We evaluated the clinical usefulness of endoscopic
      ultrasonography (EUS) for the differential diagnosis of GB wall thickening.
      METHODS: The medical records, post-operative pathology reports, and images of EUS
      for 134 patients with GB wall thickening (>3 mm) who underwent laparoscopic or
      open cholecystectomies at our institution between December 2006 and February 2010
      were retrospectively reviewed. RESULTS: Thirteen patients (9.7%) had neoplastic
      GB wall thickening (11 with adenocarcinomas and two with adenosquamous
      carcinomas) and the remaining 121 patients (90.3%) had non-neoplastic GB wall
      thickening (117 with inflammatory GB wall thickening and four with
      adenomyomatosis). The mean (+/- standard deviation [SD], mm) GB wall thickness
      was 6.5 +/- 3.3 and 19.4 +/- 7.7 for non-neoplastic and neoplastic GB wall
      thickening, respectively (P < 0.01). The EUS variables which had a statistically
      significant association with neoplastic GB wall thickening were GB wall
      thickening >10 mm, disruption of the normal two layers of the GB wall, hypoechoic
      internal echogenecity, and the absence of gallstones. Based on the multivariate
      analyses, GB wall thickening >10 mm and hypoechoic internal echogenecity were
      independent predictive factors for neoplastic GB wall thickening. CONCLUSIONS:
      The diagnostic power of EUS for differentiating neoplastic and non-neoplastic GB
      wall thickening could be improved by the appropriate application of some EUS
      variables.

PMID- 21879283
TI  - Consensus interferon used to treat prior partial-responders to pegylated
      interferon plus ribavirin.
AB  - BACKGROUND: The response to pegylated interferon (peg-IFN) plus ribavirin therapy
      remains less than ideal with 40-50% of treated subjects failing to clear the
      virus. Moreover, retreatment is only minimally effective. Consensus interferon (c
      IFN) has been shown to be efficacious in HCV genotype 1 patients who have failed
      therapy with peg-IFN. AIM: To evaluated the response to re-treatment of peg-IFN
      plus ribavirin partial-responders with c-IFN plus ribavirin. METHODS: Forty-two
      subjects who had previously failed to clear virus after treatment with peg-IFN
      plus ribavirin were treated with c-IFN (15 MUg/day) plus ribavirin (800-1,200
      mg/day) until 12 months of therapy or a total of six consecutive months of PCR
      negativity was achieved. RESULTS: The study population consisted predominantly of
      males (71%), Caucasians (76%), with African Americans comprising the remaining
      24%, subjects with HCV genotype 1 infection (81%) and 21% had cirrhosis by liver
      biopsy. The overall SVR rate was 29%. The only pretreatment variable that
      distinguished responders from partial-responders was the serum triglyceride
      level. CONCLUSIONS: The use of c-IFN plus ribavirin in the retreatment of prior
      peg-IFN plus ribavirin partial responders is essentially twice that achieved in
      prior re-treatment regimens consisting of a second course of peg-IFN plus
      ribavirin. These results will need to be evaluated against the use of triple
      therapy consisting of a peg-IFN plus ribavirin and a protease inhibitor. More
      studies utilizing c-IFN plus ribavirin with either a protease inhibitor or
      polymerase inhibitor need to be performed as well.

PMID- 21879284
TI  - Effects of RNAi-mediated matrix metalloproteinase-2 gene silencing on the
      invasiveness and adhesion of esophageal carcinoma cells, KYSE150.
AB  - BACKGROUND: Esophageal carcinoma is one of the main malignancies in China.
      Previous studies indicated that matrix metalloproteinases (MMPs) play important
      roles in the process of tumor invasion and metastasis in several types of solid
      tumors. Among all of the MMPs, MMP-2 is one of the MMPs closely associated with
      tumor invasion. In this study, we suppressed MMP-2 expression with RNA
      interference and then observed inhibitory effects on the invasion and migration
      of the esophageal carcinoma cell line KYSE150. METHODS: Three target sequences
      were selected and siRNA against MMP-2 mRNA were synthesized. After being
      transfected by the transfection complexes, the MMP-2 expression of KYSE150 cells,
      which overexpresses MMP-2, were examined by Western blot analysis and real-time
      polymerase chain reaction (PCR). Cell migration and invasion were measured with
      migration assay and Boyden chamber assays, respectively. RESULTS: RNAi against
      MMP-2 successfully inhibited the mRNA and protein expression of MMP-2 in the
      esophageal carcinoma cell line KYSE150. MMP-2 knockdown inhibited the invasion
      and migration of esophageal carcinoma cell line KYSE150. CONCLUSIONS: These
      findings suggested that the RNAi approach towards MMP-2 may be a potentially
      effective therapeutic method for the treatment of esophageal carcinoma.

PMID- 21879285
TI  - Paternal occupational exposure to pesticides and risk of neuroblastoma among
      children: a meta-analysis.
AB  - OBJECTIVE: Epidemiological data relating paternal pesticide exposure in
      occupational settings with higher risk of neuroblastoma are inconsistent. Since
      most studies included a small number of cases, lack of power is a potential
      reason for observed inconsistencies. We conducted a meta-analysis of published
      studies that investigated the association of paternal occupational pesticide
      exposure with childhood neuroblastoma. METHODS: We identified published studies
      up to October 2009 on paternal pesticide exposure and neuroblastoma using online
      databases and extracted relative risk estimates for the association. Summary
      relative risk estimates were calculated using the fixed effects inverse variance
      weighting method. To account for heterogeneity, we used Shore-corrected
      confidence intervals and the random effects method. Subgroup analyses were
      conducted according to study design, location, and exposure ascertainment method.
      RESULTS: The meta-analysis included seven case-control and two cohort studies
      with a combined total of 1,426 cases. Overall, between-study heterogeneity was
      low (p = 0.46), and the fixed effects, random effects, and Shore-adjusted
      confidence intervals were similar. The summary risk ratio was 1.07 (95% CI 0.79
      1.46, two-sided p value = 0.65). Results of the subgroup meta-analyses were
      robustly null. CONCLUSIONS: Findings from current published studies do not
      support an association between paternal occupational pesticide exposure and
      childhood neuroblastoma.

PMID- 21879286
TI  - Higher DNA repair activity is related with longer replicative life span in
      mammalian embryonic fibroblast cells.
AB  - Since the detailed comparison of DNA repair activities among mammalian embryonic
      fibroblast cells with different replicative life spans has not been investigated,
      we tested DNA repair activities in embryonic fibroblast cells derived from
      mammals including human, dog, rat, and mouse. The cell viability after treatment
      of four DNA damage agents appeared to be decreased in the order of human
      embryonic fibroblasts (HEFs) > dog embryonic fibroblasts (DEFs) > rat embryonic
      fibroblasts (REFs) > mouse embryonic fibroblasts (MEFs) although statistical
      significance was lacking. The amounts of strand breaks and AP
      (apurinic/apyrimidinic) sites also appear to be decreased in the order of HEFs >
      DEFs > REFs >= MEFs after treatment of DNA damage agents. The DNA repair
      activities and rates including base excision repair (BER), nucleotide excision
      repair (NER) and double-strand break repair (DSBR) including non-homologous end
      joining (NHEJ) decreased again in the order of HEFs > DEFs > REFs >= MEFs. BER
      and NHEJ activities in 3% O(2) also decreased in the order of HEFs > DEFs > REFs
      > MEFs. This order in DNA repair activity appears to be coincident with that of
      replicative life span of fibroblasts and that of life span of mammals. These
      results indicate that higher DNA repair activity is related with longer
      replicative life span in embryonic fibroblast cells.

PMID- 21879287
TI  - B cell immunosenescence: different features of naive and memory B cells in
      elderly.
AB  - Elderly people show a reduced protection against new infections and a decreased
      response to vaccines as a consequence of impairment of both cellular and humoral
      immunity. In this paper we have studied memory/naive B cells in the elderly,
      evaluating surface immunoglobulin expression, production of the pro- and anti
      inflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)
      10, and presence of somatic hypermutation, focusing on the IgG(+)IgD(-)CD27(-)
      double negative (DN) B cells that are expanded in the elderly. Our results show
      that naive B cells from young donors need a sufficiently strong stimulus to be
      activated "in vitro", while naive B cells from old subjects are able to produce
      IL-10 and TNF-alpha when stimulated "physiologically" (alpha-CD40/IL-4),
      suggesting that these cells might play a role in the control of the immuno
      inflammatory environment in the elderly. In addition, in the elderly there is an
      accumulation of DN B cells with a reduced rate of somatic hypermutation. Thus, DN
      B lymphocytes may be exhausted cells that are expanded and accumulate as a by
      product of persistent stimulation or impaired germinal center formation.

PMID- 21879288
TI  - Vascular access in transcatheter aortic valve implantation.
AB  - The positive early experiences with TAVI however, revealed that vascular access
      remains a hindrance to broader application and success of the procedure. This
      article will review the most common vascular routes used to deliver transcatheter
      aortic valves, and describe a new technique via the right axillary/subclavian
      artery approach.

PMID- 21879289
TI  - Dysfunction of TGF-beta1 signaling in Alzheimer's disease: perspectives for
      neuroprotection.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder that affects about 35
      million people worldwide. Current drugs for AD only treat the symptoms and do not
      interfere with the underlying pathogenic mechanisms of the disease. AD is
      characterized by the presence of beta-amyloid (Abeta) plaques, neurofibrillary
      tangles, and neuronal loss. Identification of the molecular determinants
      underlying Abeta-induced neurodegeneration is an essential step for the
      development of disease-modifying drugs. Recently, an impairment of the
      transforming growth factor-beta1 (TGF-beta1) signaling pathway has been
      demonstrated to be specific to the AD brain and, particularly, to the early phase
      of the disease. TGF-beta1 is a neurotrophic factor responsible for the initiation
      and maintenance of neuronal differentiation and synaptic plasticity. The
      deficiency of TGF-beta1 signaling is associated with Abeta pathology and
      neurofibrillary tangle formation in AD animal models. Reduced TGF-beta1 signaling
      seems to contribute both to microglial activation and to ectopic cell-cycle re
      activation in neurons, two events that contribute to neurodegeneration in the AD
      brain. The neuroprotective features of TGF-beta1 indicate the advantage of
      rescuing TGF-beta1 signaling as a means to slow down the neurodegenerative
      process in AD.

PMID- 21879290
TI  - Wnt5a plays a crucial role in determining tooth size during murine tooth
      development.
AB  - We have previously demonstrated that tooth size is determined by dental
      mesenchymal factors. Exogenous bone morphogenetic protein (BMP)4, Noggin,
      fibroblast growth factor (FGF)3 and FGF10 have no effect on tooth size, despite
      the expressions of Bmp2, Bmp4, Fgf3, Fgf10 and Lef1 in the dental mesenchyme.
      Among the wingless (Wnt) genes that are differentially expressed during tooth
      development, only Wnt5a is expressed in the dental mesenchyme. The aims of the
      present study were to clarify the expression pattern of Wnt5a in developing tooth
      germs and the role of Wnt5a in the regulation of tooth size by treatment with
      exogenous WNT5A with/without an apoptosis inhibitor on in vitro tooth germs
      combined with transplantation into kidney capsules. Wnt5a was intensely expressed
      in both the dental epithelium and mesenchyme during embryonic days 14-17,
      overlapping partly with the expressions of both Shh and Bmp4. Moreover, WNT5A
      retarded the development of tooth germs by markedly inducing cell death in the
      non-dental epithelium and mesenchyme but not widely in the dental region, where
      the epithelial-mesenchymal gene interactions among Wnt5a, Fgf10, Bmp4 and Shh
      might partly rescue the cells from death in the WNT5A-treated tooth germ.
      Together, these results indicate that WNT5A-induced cell death inhibited the
      overall development of the tooth germ, resulting in smaller teeth with blunter
      cusps after tooth-germ transplantation. Thus, it is suggested that Wnt5a is
      involved in regulating cell death in non-dental regions, while in the dental
      region it acts as a regulator of other genes that rescue tooth germs from cell
      death.

PMID- 21879291
TI  - Moral learning in an integrated social and healthcare service network.
AB  - The traditional organizational boundaries between healthcare, social work, police
      and other non-profit organizations are fading and being replaced by new
      relational patterns among a variety of disciplines. Professionals work from their
      own history, role, values and relationships. It is often unclear who is
      responsible for what because this new network structure requires rules and
      procedures to be re-interpreted and re-negotiated. A new moral climate needs to
      be developed, particularly in the early stages of integrated services. Who should
      do what, with whom and why? Departing from a relational and hermeneutic
      perspective, this article shows that professionals in integrated service networks
      embark upon a moral learning process when starting to work together for the
      client's benefit. In this context, instrumental ways of thinking about
      responsibilities are actually counterproductive. Instead, professionals need to
      find out who they are in relation to other professionals, what core values they
      share and what responsibilities derive from these aspects. This article
      demonstrates moral learning by examining the case of an integrated social service
      network. The network's development and implementation were supported by
      responsive evaluation, enriched by insights of care ethics and hermeneutic
      ethics.

PMID- 21879292
TI  - Sequential chemotherapy and myeloablative allogeneic hematopoietic stem cell
      transplantation for refractory acute lymphoblastic leukemia.
AB  - The prognosis of patients receiving allogeneic hematopoietic stem cell
      transplantation (HSCT) for refractory acute lymphoblastic leukemia (ALL) is very
      poor. To improve survival rates, we attempted to intensify the conditioning
      regimen with daunorubicin, vincristine, prednisolone, medium-dose etoposide,
      cyclophosphamide, and total body irradiation (DNR/VCR/PSL plus medium-dose
      VP/CY/TBI). Four patients in relapse or induction failure of B-precursor ALL
      without other complications underwent allogeneic HSCT. Initially, chemotherapy
      comprising DNR 60 mg/m(2) for 3 days, VCR 1.4 mg/m(2) for 1 day, and PSL 60
      mg/m(2) for 3 days was administered, which was followed by medium-dose VP/CY/TBI;
      some modifications were made for individual patients. All patients achieved
      engraftment and complete remission after HSCT. Regimen-related toxicities were
      tolerable and no patient died within 100 days. Two patients were alive without
      disease on days 563 and 1,055. The third patient relapsed on day 951, while the
      fourth died on day 179 without disease. Our results indicate that intensified
      myeloablative HSCT should be considered for patients with refractory ALL.

PMID- 21879294
TI  - Adhesion and biofilm formation of Mycoplasma pneumoniae on an abiotic surface.
AB  - We demonstrated that when M. pneumoniae was grown on an abiotic surface of either
      glass or polystyrene with a serum-containing medium, the bacteria adhered to the
      surface and formed highly differentiated volcano-like biofilm structures. As
      adherence to the surface and/or biofilm formation was totally inhibited by anti
      P1 polyclonal monospecific antibodies, we suggest that the adherence of M.
      pneumoniae to the abiotic surface and/or biofilm formation is associated with P1,
      the major tip organelle protein of this organism. Furthermore, adherence and/or
      biofilm formation was markedly inhibited by treating the serum component of the
      growth medium with neuraminidase or by growing the bacteria in the presence of
      sialyllactose, suggesting that the initial step in the adherence to and/or
      biofilm formation by M. pneumoniae on an abiotic surface is the interaction of
      the bacterium through its tip organelle with sialic acid residues of serum
      glycoproteins.

PMID- 21879293
TI  - Methylation-specific ligation detection reaction (msLDR): a new approach for
      multiplex evaluation of methylation patterns.
AB  - A new sensitive method for multiplex gene-specific methylation analysis was
      developed using a ligation-based approach combined with a TaqMan-based detection
      and readout employing universal reporter probes. The approach, termed methylation
      specific Ligation Detection Reaction (msLDR), was applied to test 16 loci in 8
      different colorectal cancer cells in parallel. These loci encode immune
      regulatory genes involved in T-cell and natural killer cell activation, whose
      silencing is associated with the development or progression of colorectal cancer.
      Parallel analysis of HLA-A, HLA-B, STAT1, B2M, LMP2, LMP7, PA28alpha, TAP1, TAP2,
      TAPBP, ULBP2 and ULBP3 by msLDR in eight colorectal cancer cell lines showed
      preferential methylation at the HLA-B, ULBP2 and ULBB3 loci, but not at the other
      loci. MsLDR was found to represent a suitable and sensitive method for the
      detection of distinct methylation patterns as validated by conventional
      bisulphite Sanger sequencing and COBRA analysis. Since gene silencing by
      epigenetic mechanisms plays a central role during transformation of a normal
      differentiated somatic cell into a cancer cell, characterization of the gene
      methylation status in tumours is a major topic not only in basic research, but
      also in clinical diagnostics. Due to a very simple workflow, msLDR is likely to
      be applicable to clinical samples and thus comprises a potential diagnostic tool
      for clinical purposes.

PMID- 21879295
TI  - Animal tumor models for PET in drug development.
AB  - Positron emission tomography (PET) is being increasingly applied to animal tumor
      models due to the need for proof-of-concept testing and preclinical efficacy
      studies of anticancer agents. Regardless of the nature of an experiment,
      investigators should carefully select a suitable animal tumor model as part of
      the experimental design. This review introduces sources of information and the
      guiding principles regarding applicability of various animal tumor models for PET
      in anticancer agent development especially for small animals.

PMID- 21879296
TI  - The value of 18F-FDG-PET/CT in the differential diagnosis of solitary pulmonary
      nodules in areas with a high incidence of tuberculosis.
AB  - OBJECTIVE: The purpose of this study was to evaluate (18)F-FDG-PET, PET/CT, and
      CT in the diagnosis of benign or malignant solitary pulmonary nodules (SPNs) in
      areas with a high incidence of TB. METHODS: Ninety-six patients with a SPN
      smaller than 30 mm were studied prospectively. PET/CT images were obtained 60 min
      after intravenous injection of (18)F-FDG. The data obtained for each patient were
      analyzed and the accuracy, sensitivity, specificity, positive predictive value
      (PPV), and negative predictive value (NPV) were calculated and compared using
      chi(2) test. RESULTS: The sensitivity, specificity, accuracy, PPV, and NPV in the
      diagnosis of SPN were 86.7, 72.2, 81.3, 83.9, and 76.5%, respectively, for CT and
      88.3, 61.1, 79.1, 79.1, and 75.9%, respectively, for PET. Tuberculosis was
      responsible for 57.1% (8/14) of false-positives on PET. The sensitivity,
      specificity, accuracy, PPV, and NPV in the diagnosis of SPN were 96.7, 75.7,
      88.5, 88.1, and 94.4% for PET/CT. The accuracy of PET/CT was higher than that of
      either CT or PET alone (P < 0.05). CONCLUSION: PET has a high false-positive rate
      in areas with a high incidence of TB; combined PET and CT (PET/CT) can improve
      the diagnostic accuracy in the differentiation of an SPN.

PMID- 21879297
TI  - Cis-trans photoisomerization properties of GFP chromophore analogs.
AB  - The photoswitching behaviour of the green fluorescent protein (GFP) chromophore
      and its analogs opens up exciting horizons for the engineering and development of
      molecular devices for high sensitivity in vivo studies. In this work we present
      the synthesis and photophysical study of four GFP chromophore analogs belonging
      to butenolide and pyrrolinone classes. These chromophores possess an intriguing
      photoinduced cis-trans isomerization mechanism. Stereochemical structural
      assignment was unambiguously performed by 1D Nuclear Overhauser Effect NMR
      measurements. The spectroscopic properties of both cis and trans isomers were
      studied, and photoconversion quantum yield for cis-trans isomerization was
      assessed to be in the 0.1-0.4 range. Finally, the 3J(C,H) coupling constant in
      the 13C-C=C-H motif was in excellent agreement with theoretical DFT calculations,
      thus providing a further confirmation of cis-trans photoisomerization of the
      structurally analog GFP chromophore.

PMID- 21879298
TI  - Single-pot derivatisation strategy for enhanced gliotoxin detection by HPLC and
      MALDI-ToF mass spectrometry.
AB  - Gliotoxin is produced by non-ribosomal peptide synthesis and secreted from
      certain fungi, including Aspergillus fumigatus. It is an
      epipolythiodioxopiperazine that contains an intact disulphide bridge and is the
      focus of intense research as a consequence of its negative immunomodulatory
      properties. Gliotoxin detection is generally enabled by reversed-phase-high
      performance liquid chromatography (RP-HPLC), with absorbance detection (220-280
      nm), or liquid chromatography-mass spectrometry, yet detection is not readily
      achievable by matrix-assisted laser desorption ionisation-time-of-flight mass
      spectrometry (MALDI-ToF MS). We have developed a single-pot derivatisation
      strategy which uses sodium borohydride-mediated reduction of gliotoxin followed
      by immediate alkylation of exposed thiols by 5'-iodoacetamidofluorescein to yield
      a stable product, diacetamidofluorescein-gliotoxin (GT-(AF)(2)), of molecular
      mass 1103.931 Da ((M+H)+). This product is readily detectable by RP-HPLC and
      exhibits a 6.8-fold increase in molar absorptivity compared with gliotoxin, which
      results in a higher sensitivity of detection (40 ng; 125 pmoL). GT-(AF)(2) also
      fluoresces (excitation/emission, 492:518 nm). Unlike free gliotoxin, the product
      (>800 fmol) is detectable by MALDI-ToF MS. Sporidesmin A can also be detected by
      RP-HPLC and MALDI-ToF MS (>530 fmol) using this strategy. We also demonstrate
      that the strategy facilitates detection of gliotoxin (mean +/- SD = 3.55 +/- 0.07
      MUg 100 MUL(-1); n = 2) produced by A. fumigatus, without the requirement for
      organic extraction of culture supernatants and associated solvent removal. GT
      (AF)(2) is also detectable (150 ng; 460 pmol) by thin-layer chromatography.

PMID- 21879299
TI  - Could smaller really be better? Current and future trends in high-resolution
      microcoil NMR spectroscopy.
AB  - NMR is an invaluable analytical technique that provides structural and chemical
      information about a molecule without destroying the sample. However, NMR suffers
      from an inherent lack of sensitivity compared to other popular analytical
      techniques. This trends article focuses on strategies to increase the sensitivity
      of NMR using solenoidal microcoil, microstrip, and microslot probes. The role of
      these reduced-volume receiver coils for detection in hyphenated capillary
      electrophoresis (CE) and capillary isotachophoresis (cITP) NMR experiments is
      discussed. Future directions will likely build on work to develop probes
      containing multiple coils for high-throughput NMR and field-portable instruments.

PMID- 21879301
TI  - [Traumatic dissection of carotid arteries caused by high energy motorcycle
      accident].
AB  - Injuries of internal carotid arteries caused by high energy trauma are rare but
      often combined with poor outcome. Blunt trauma to the head and neck as well as
      the use of newer motorcycle helmets together with crash circumstances should
      promptly lead to a differentiated polytrauma management with expansion of
      radiologic diagnostics. This could lead to a reduction of overlooked dissections
      and an increase in promptly and correctly treated injuries.

PMID- 21879300
TI  - Hydrophilic interaction liquid chromatography (HILIC)--a powerful separation
      technique.
AB  - Hydrophilic interaction liquid chromatography (HILIC) provides an alternative
      approach to effectively separate small polar compounds on polar stationary
      phases. The purpose of this work was to review the options for the
      characterization of HILIC stationary phases and their applications for
      separations of polar compounds in complex matrices. The characteristics of the
      hydrophilic stationary phase may affect and in some cases limit the choices of
      mobile phase composition, ion strength or buffer pH value available, since
      mechanisms other than hydrophilic partitioning could potentially occur. Enhancing
      our understanding of retention behavior in HILIC increases the scope of possible
      applications of liquid chromatography. One interesting option may also be to use
      HILIC in orthogonal and/or two-dimensional separations. Bioapplications of HILIC
      systems are also presented.

PMID- 21879302
TI  - [The influence of timing of surgery on mortality and early complications in
      femoral neck fractures, by surgical procedure: an analysis of 22,566 cases from
      the German External Quality Assurance Program].
AB  - BACKGROUND: The current S2 guideline recommends treatment of a femoral neck
      fracture within the first 24 h; this becomes evident by the significant rise in
      general and early surgical complications, when the surgical treatment was delayed
      for more than 48 h. The influence of different surgical procedures was
      investigated. PATIENTS UND METHODS: A total of 22,566 records from the external
      Quality Assurance Program in North Rhine-Westphalia for treatment of femoral neck
      fractures in 2004/2005 (BQS specification 7.0 and 8.0) were risk-adjusted and
      evaluated. RESULTS: Surgery was performed within 48 h in 83.9% of the patients. A
      significant rise in general and early surgical complications was registered when
      the surgical treatment was delayed for more than 48 h. Mortality and general
      complications were significantly lower for percutaneous screw fixation. All kinds
      of joint replacement show significantly higher general and surgical
      complications. CONCLUSION: The analyzed data support the rating of femoral neck
      fracture as requiring the intervention of urgent early surgery, as stated in the
      guideline. Percutaneous screw fixation can be considered for immobile and
      multimorbid patients with undislocated fractures. Advantages of total hip
      replacement compared to hemiarthroplasty cannot be supported by the QS-NRW data.

PMID- 21879303
TI  - [Patient safety].

PMID- 21879304
TI  - [Injuries of the midfoot].
AB  - Injuries of the midfoot are often missed and therefore underestimated. The
      diagnosis and primary treatment are crucial for the outcome. An accurately made
      diagnosis and therapy initially can anticipate the extent of post-traumatic
      malpositioning, arthrosis and the number of subsequent surgeries. Diagnostics
      should liberally include computed tomography with multiplanar reconstructions;
      clinically a compartment syndrome should be treated at an early stage. Surgery
      includes anatomical reconstruction of the relevant joints and ligamentous
      structures and restoration of axes and lengths of the columns of the foot.
      Innovations comprise intraoperative 3-D imaging and computer-assisted surgery for
      quality control. New methods for ligamentous injuries are transosseous suturing
      and endobutton techniques, which have not yet become established.

PMID- 21879305
TI  - Tuberculosis of breast: unusual manifestation of tuberculosis.
AB  - Tuberculosis affects almost every organ of the body, and the breast is no
      exception. However, tuberculosis of the breast is rare, and the varied
      presentation requires a high index of suspicion, especially in middle-aged women
      for whom a clinical diagnosis of malignancy is likely to be made. We report two
      cases of primary tuberculosis of breast with different manifestations. One case
      presented as tuberculous mastitis and the other presented with a lump
      masquerading as breast carcinoma. The diagnosis in both cases was based on
      demonstration of acid-fast bacilli on histopathological examination. Resolution
      was complete with antitubercular therapy, and major surgical intervention was not
      necessary.

PMID- 21879306
TI  - Mediterranean spotted fever and encephalitis: a case report and review of the
      literature.
AB  - Mediterranean spotted fever (MSF) is a disease caused by Rickettsia conorii and
      transmitted by the brown dog tick Rhipicephalus sanguineus. It is widely
      distributed through southern Europe, Africa, and the Middle East. It is an
      emerging or a reemerging disease in some regions. Countries of the Mediterranean
      basin, such as Portugal, have noticed an increased incidence of MSF over the past
      10 years. It was believed that MSF was a benign disease associated with a
      mortality rate of 1-3% before the antimicrobial drug era. It was called benign
      summer typhus. Severe forms were described in 1981, and the mortality rate
      reached 32% in Portugal in 1997. However, neurological manifestations associated
      with brain lesions are a rare event. We describe the case of a man with fever,
      maculopapular rash, a black spot, and hemisensory loss including the face on the
      left side of the body with brain lesions in the imaging studies.

PMID- 21879307
TI  - Up-regulated biglycan expression correlates with the malignancy in human
      colorectal cancers.
AB  - Biglycan, an extracellular matrix protein, has been implicated in the oncogenesis
      and cancer development in various types of human cancer. The clinical
      significance of biglycan in colorectal cancer, however, remains unclear. In the
      present study, biglycan mRNA expression was analyzed in 110 samples (primary
      colorectal tumor and matched adjacent normal tissue) derived from 55 patients
      with colorectal cancer using quantitative real-time RT-PCR. The correlations
      between biglycan up-regulation and the clinicopathological data were also
      evaluated. We found that the up-regulation of biglycan occurred in 61.8% (34/55)
      of colorectal cancer tissues, and biglycan expression in colorectal cancer
      tissues was markedly higher than that in corresponding normal tissues (P =
      0.0264). Moreover, statistical analysis displayed a significant correlation in
      biglycan up-regulation with poor tumor differentiation (P = 0.009), lymph node
      metastasis (P = 0.041), and distant metastasis (P = 0.036). However, there was no
      significant correlation between biglycan up-regulation and other
      clinicopathological factors (all P > 0.05). In conclusion, biglycan may be a
      potential marker for the malignancy of colorectal cancer.

PMID- 21879308
TI  - Erdheim-Chester disease with multisystem involvement in a 4-year-old.
AB  - Erdheim-Chester disease is a rare form of non-Langerhans histiocytosis of unknown
      origin occurring mainly in adults. It is extremely rare in children. We report a
      case of a 4-year-old boy with Erdheim-Chester disease that initially presented as
      hemifacial palsy and bone pain with multisystem involvement. We describe
      radiographic findings of bones that show characteristic bilateral symmetrical
      osteosclerosis with atypical osteolytic lesions in addition to CT findings for
      pulmonary involvement and MR findings for intracranial lesions.

PMID- 21879309
TI  - Hydrophilic acrylic intraocular lens optic opacification in a diabetic patient.
AB  - PURPOSE: To report clinicopathologic and ultrastructural feature of one opacified
      hydrophilic acrylic intraocular lens (IOL) explanted from a diabetic patient.
      METHODS: A 48-year-old man underwent trans pars plana vitrectomy and
      phacoemulsification with implantation of a hydrophilic acrylic lens OS in
      November 2008. The patient complained of a marked decrease in visual acuity in
      May 2009 as a result of a milky opalescence of the IOL. Intraocular lens
      explantation and exchange were performed in August 2009, and the explanted IOL
      was submitted to our center for detailed pathologic, histochemical and
      ultrastructural evaluation. It was stained by the von Kossa method for calcium,
      and also underwent scanning electron microscopy and energy dispersive radiograph
      spectroscopy to ascertain the nature of the deposits leading to opacification.
      RESULTS: Opacification of the IOL was found to be the cause of the decreased
      visual acuity. The opacification involved only the IOL optic, and the haptics was
      clear. Histochemical and ultrastructural analyses revealed that the opacity was
      caused by deposition of calcium and phosphate within the lens optic. CONCLUSION:
      We believe this report of calcification of the Akreos((r)) MI-60 IOL is of
      clinicopathological importance. Long-term follow-up of diabetic patients
      implanted with this IOL should be maintained by surgeons and manufacturers.

PMID- 21879310
TI  - PMS: photosystem I electron donor or fluorescence quencher.
AB  - Light energy harvested by the pigments in Photosystem I (PSI) is used for charge
      separation in the reaction center (RC), after which the positive charge resides
      on a special chlorophyll dimer called P700. In studies on the PSI trapping
      kinetics, P700(+) is usually chemically reduced to re-open the RCs. So far, the
      information available about the reduction rate and possible chlorophyll
      fluorescence quenching effects of these reducing agents is limited. This
      information is indispensible to estimate the fraction of open RCs under known
      experimental conditions. Moreover, it would be important to understand if these
      reagents have a chlorophyll fluorescence quenching effects to avoid the
      introduction of exogenous singlet excitation quenching in the measurements. In
      this study, we investigated the effect of the commonly used reducing agent
      phenazine methosulfate (PMS) on the RC and fluorescence emission of higher plant
      PSI-LHCI. We measured the P700(+) reduction rate for different PMS
      concentrations, and show that we can give a reliable estimation on the fraction
      of closed RCs based on these rates. The data show that PMS is quenching
      chlorophyll fluorescence emission. Finally, we determined that the fluorescence
      quantum yield of PSI with closed RCs is 4% higher than if the RCs are open.

PMID- 21879311
TI  - Nitric oxide synthase inhibition abrogates hydrogen sulfide-induced
      cardioprotection in mice.
AB  - The cardioprotective property of hydrogen sulfide (H(2)S) is recently reported.
      However, cellular signaling cascades mediated by H(2)S are largely unclear. This
      study was undertaken to explore the molecular mechanism of H(2)S-induced
      cardioprotection in mouse heart by utilizing in vivo model of cardiac injury. We
      report here that intraperitoneal administration of sodium hydrogen sulfide (NaHS,
      50 MUmol kg(-1 )day(-1) for 2 days), a H(2)S donor, significantly (P <= 0.05)
      increased nitric oxide levels in serum as well as myocardium without any sign of
      myocardial injury. Typical characteristics of myocardial injury induced by
      isoproterenol (ISO) administration was significantly (P <= 0.05) abrogated by
      NaHS administration as evidenced from reduction in elevated thiobarbituric acid
      reactive substances (TBARS) and normalization of glutathione (GSH), glutathione
      peroxidase, superoxide dismutase (SOD), and catalase activity. Further, decrease
      in TNF-alpha expression and improvement in myocardial architecture was also
      observed. However, co-administration of N-nitro-L-arginine methyl ester, a nitric
      oxide synthase (NOS) inhibitor, and Celecoxib, a selective cyclooxygenase-2 (COX
      2) inhibitor along with NaHS and ISO abrogated the beneficial effect of H(2)S
      differentially. Inhibition of NOS significantly (P <= 0.05) increased serum
      creatine kinase, lactate dehydrogenase, serum glutamic oxaloacetic transaminase
      activity and myocardial TBARS, along with significant (P <= 0.05) reduction of
      myocardial GSH, SOD, and catalase. This was followed by increase in TNF-alpha
      expression and histopathological changes. Our results revealed that H(2)S
      provides myocardial protection through interaction with NOS and COX-2 pathway and
      inhibition of NOS completely abrogates the hydrogen sulfide-induced
      cardioprotection in mice.

PMID- 21879312
TI  - Potential preventive effect of carvacrol against diethylnitrosamine-induced
      hepatocellular carcinoma in rats.
AB  - Antioxidants are one of the key players in tumorigenesis, several natural and
      synthetic antioxidants were shown to have anticancer effects. The aim of the
      present study is to divulge the chemopreventive nature of carvacrol during
      diethylnitrosamine (DEN)-induced liver cancer in male wistar albino rats.
      Administration of DEN to rats resulted in increased relative liver weight and
      serum marker enzymes aspartate transaminase (AST), alanine transaminase (ALT),
      alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and gamma glutamyl
      transpeptidase (gammaGT). The levels of lipid peroxides elevated (in both serum
      and tissue) with subsequent decrease in the final body weight and tissue
      antioxidants like superoxide dismutase (SOD), catalase (CAT), reduced glutathione
      (GSH), glutathione peroxidase (GPx), and glutathione reductase (GR). Carvacrol
      supplementation (15 mg/kg body weight) significantly attenuated these
      alterations, thereby showing potent anticancer effect in liver cancer.
      Histological observations and transmission electron microscopy studies were also
      carried out, which added supports to the chemopreventive action of the carvacrol
      against DEN-induction during liver cancer progression. These findings suggest
      that carvacrol prevents lipid peroxidation, hepatic cell damage, and protects the
      antioxidant system in DEN-induced hepatocellular carcinogenesis.

PMID- 21879313
TI  - Genotype rs8099917 near the IL28B gene and amino acid substitution at position 70
      in the core region of the hepatitis C virus are determinants of serum
      apolipoprotein B-100 concentration in chronic hepatitis C.
AB  - The life cycle of the hepatitis C virus (HCV) is closely related to host
      lipoprotein metabolism. Serum levels of lipid are associated with the response to
      pegylated interferon plus ribavirin (PEG-IFN/RBV) therapy, while single
      nucleotide polymorphisms (SNPs) around the human interleukin 28B (IL28B) gene
      locus and amino acid substitutions in the core region of the HCV have been
      reported to affect the efficacy of PEG-IFN/RBV therapy in chronic hepatitis with
      HCV genotype 1b infection. The aim of this study was to elucidate the
      relationship between serum lipid and factors that are able to predict the
      efficacy of PEG-IFN/RB therapy, with specific focus on apolipoprotein B-100 (apoB
      100) in 148 subjects with chronic HCV G1b infection. Our results demonstrated
      that both the aa 70 substitution in the core region of the HCV and the rs8099917
      SNP located proximal to the IL28B were independent factors in determining serum
      apoB-100 and low-density lipoprotein (LDL) cholesterol levels. A significant
      association was noted between higher levels of apoB-100 (P = 1.1 * 10(-3)) and
      LDL cholesterol (P = 0.02) and the subjects having Arg70. A significant
      association was also observed between subjects carrying the rs8099917 TT
      responder genotype and higher levels of apoB-100 (P = 6.4 * 10(-3)) and LDL
      cholesterol (P = 4.2 * 10(-3)). Our results suggest that apoB-100 and LDL
      cholesterol are markers of impaired cellular lipoprotein pathways and/or host
      endogenous interferon response to HCV in chronic HCV infection. In particular,
      serum apoB-100 concentration might be an informative marker for judging changes
      in HCV-associated intracellular lipoprotein metabolism in patients carrying the
      rs8099917 responder genotype.

PMID- 21879314
TI  - Association of cognitive performance with interleukin-6 receptor Asp358Ala
      polymorphism in healthy adults.
AB  - Wechsler adult intelligence scale-revised was performed in 576 healthy adults to
      examine whether a functional polymorphism (Asp358Ala) of the IL-6 receptor (IL
      6R) gene is associated with cognitive performance. Verbal intelligence quotient
      in Asp homozygotes was significantly higher compared to Ala carriers (P = 0.005).
      Compared to Ala carriers, Asp homozygotes performed better in the verbal subtests
      requiring long-term memory stores. Elevated IL-6 and soluble IL-6R levels in Ala
      carriers may have negative impact on acquiring verbal cognitive ability requiring
      long-term memory.

PMID- 21879315
TI  - Intravenous leiomyomatosis: CT findings.
AB  - Intravenous leiomyomatosis (IVL) is a rare smooth muscle tumor. Although IVL is
      histologically benign, it might be aggressive in its behavior and can grow into
      pelvic veins and the inferior vena cava (IVC) extending into the heart chambers
      and pulmonary vasculature. Occasionally, it was found to have lung metastasis. We
      describe four cases of IVL in the IVC with a history of hysterectomy for uterine
      leiomyoma, one extending into the left renal vein and three growing into the
      right heart chamber. We report the computed tomography (CT) findings in the four
      cases and briefly discuss the CT features of IVL in order to help making
      accurately preoperative diagnosis and improve the rate of surgical resection and
      survival.

PMID- 21879316
TI  - MRI of Crohn's disease: from imaging to pathology.
AB  - Technological advances in the area of magnetic resonance imaging (MRI) raised
      expectations on the potential role of this imaging modality for evaluation of the
      gastrointestinal tract, especially on Crohn's disease (CD), based on the high
      spatial and tissue resolution as well as lack of ionizing radiation. Available
      evidence indicates that MRI has a high diagnostic accuracy for the detection of
      disease activity, location of the lesions, and also for determining the severity
      of the disease, which together are the main aspects for the therapeutic decision
      making in patients with CD. MRI provides a high accuracy in detection of
      strictures, characterization of fistulizing lesions and extraluminal
      complications such us abscesses which are a key finding for considering medical
      and surgical options. Knowledge of the pathological substrate of inflammatory
      lesions in CD as well as extraenteric lesions may improve diagnostic image
      interpretation, and thus contribute to optimize patient care.

PMID- 21879317
TI  - Contrast-enhanced ultrasound in abdominal imaging.
AB  - The administration of a contrast agent is considered an essential tool to
      evaluate abdominal diseases using Ultrasound. The most targeted organ is the
      liver, especially to characterize focal liver lesions and to assess the response
      to percutaneous treatment. However, the expanding abdominal indications of
      contrast-enhanced ultrasound make this technique an important tool in the
      assessment of organ perfusion including the evaluation of ischemic, traumatic,
      and inflammatory diseases.

PMID- 21879318
TI  - Late diagnosis of medial condyle fracture of the humerus with rotational
      displacement in a child.
AB  - For displaced medial condyle fractures in children, open reduction with internal
      fixation seems to be most popular treatment method. The major complication of
      this method is failure to make the proper early diagnosis. Corrective
      supracondylar humeral osteotomy has been preferred to open reduction and internal
      fixation for managing malunited fragments. We report a case of a child with
      nonunion of the medial condyle of the humerus who was subsequently treated
      successfully with open reduction and internal fixation.

PMID- 21879320
TI  - A comparison of islet autotransplantation with allotransplantation and factors
      elevating acute portal pressure in clinical islet transplantation.
AB  - BACKGROUND: Acute portal pressure rise is occasionally observed during
      intraportal islet infusion, especially in islet autotransplantation (IAT) where
      tissue purification is rarely applied. In this paper we investigate factors
      associated with acute portal pressure rise, a known risk factor for portal vein
      thrombosis. METHODS: Retrospective data was collected on 15 islet autotransplant
      and 122 allogeneic islet transplant subjects. Non-purified pancreatic cells were
      transplanted in islet autotransplants, and purified islet cells were transplanted
      in allogeneic transplants. Portal pressure was documented throughout the islet
      infusion. RESULTS: The total numbers of transplanted islets were significantly
      smaller in autotransplants than allografts, although the packed cell volume in
      autotransplants was larger. Autoislet infusion, with a larger packed cell volume,
      caused higher transient portal venous pressures than allogeneic islet transplant.
      Univariate analysis and multivariate linear regression revealed that packed cell
      volume and the number of transplanted cells were significant risk factors for
      acute portal pressure rise in both autotransplants and allogeneic transplants.
      CONCLUSIONS: Non-purified IAT has a higher risk for acute portal pressure rise
      than allogeneic islet transplantation, and the rise is associated with the packed
      cell volume and the number of transplanted cells. Minimization of packed cell
      volume and cautious monitoring of portal pressure are important to avoid
      potential complications of portal hypertension.

PMID- 21879319
TI  - Peer victimization in youth with Tourette syndrome and other chronic tic
      disorders.
AB  - Chronic tic disorders including Tourette syndrome have negative impact across
      multiple functional domains. We explored associations between peer victimization
      status and tic subtypes, premonitory urges, internalizing symptoms, explosive
      outbursts, and quality of life among youth with chronic tic disorders, as part of
      the internet-based omnibus Tourette Syndrome Impact Survey. A mixed methods
      design combined child self-report and parental proxy-report (i.e., parent
      reporting on the child) demographic and quantitative data for affected youth ages
      10-17 years addressing gender, mean age, ethnicity and other socioeconomic
      features, and presence of tic disorders and co-occurring psychiatric disorders.
      Peer "Victim" versus "Non-victim" status was determined using a subset of four
      questions about being bullied. "Victim" status was identified for those youth who
      endorsed the frequency of the occurrence of being bullied in one or more of the
      four questions as "most of the time" or "all of the time". Data from 211 eligible
      youth respondents and their parents/guardians showed 26% reporting peer
      victimization. Victim status was associated with greater tic frequency,
      complexity and severity; explosive outbursts; internalizing symptoms; and lower
      quality of life. Peer victimization among youth with chronic tic disorders is
      common and appears associated with tic morbidity, anxiety, depression, explosive
      outbursts, and poorer psychosocial functioning. Anticipatory guidance, specific
      bullying screening and prevention, and further studies are indicated in this
      population.

PMID- 21879321
TI  - The prognosis after curative resection of gallbladder cancer with hilar invasion
      is similar to that of hilar cholangiocarcinoma.
AB  - BACKGROUND/PURPOSE: Gallbladder cancer (GBC) often invades the hepatic hilum and
      even small tumors can cause obstructive jaundice. Operative intervention for GBC
      with obstructive jaundice is sometimes not recommended because it is associated
      with a poor prognosis. However, the extended procedure is recommended for
      patients with hilar cholangiocarcinoma (HC). We therefore compared the
      postoperative survival of patients with GBC invading the hepatic hilum with that
      with HC. METHODS: Between 1998 and 2008, 27 patients with GBC invasion of the
      hepatic hilum (hGBC) and 124 with HC underwent surgical resection with curative
      intent in the Department of Surgical Oncology, Hokkaido University Graduate
      School of Medicine. This study included patients with GBC without peritoneal
      dissemination and liver or para-aortic lymph node metastasis. Extended right
      hemihepatectomy and extrahepatic bile duct resection comprise the treatment of
      choice for GBC with hilar invasion (hGBC). We aimed to achieve R0 outcomes by
      aggressive vascular resection and/or concomitant resection of directly invaded
      organs around the GBC along with extended right hemihepatectomy. RESULTS: We
      analyzed 27 patients with hGBC (age 58-83 years; median 71 years; male:female
      13:14) and 124 with HC (age 45-80 years; median 69 years; male:female 94:30). The
      3- and 5-year survival rates of 43 and 24% for hGBC and 58 and 38% for HC,
      respectively, did not differ significantly (p = 0.14). Preoperative obstructive
      jaundice was a complication in 22 (81%) and 95 (77%) patients with hGBC and HC,
      respectively. The 5-year survival rates were 40 and 36%, respectively, which did
      not differ significantly (p = 0.61). The 5-year survival rates after extended
      right hemihepatectomy to resect the tumor with curative intent were 34 and 34%
      for hGBC and HC, which did not differ significantly (p = 0.14). CONCLUSIONS: The
      prognosis after curative resection of GBC with hilar invasion is similar to that
      of HC in selected patients. Aggressive surgery for advanced GBC with hilar
      invasion might increase survival rates.

PMID- 21879322
TI  - Role of death receptor, mitochondrial and endoplasmic reticulum pathways in
      different stages of degenerative human lumbar disc.
AB  - Intervertebral disc (IVD) cell apoptosis has been suggested to play an important
      role in promoting the degeneration process. It has been demonstrated that IVD
      cell apoptosis occurs through either death receptor, mitochondrial or endoplasmic
      reticulum (ER) pathway. Our study aimed to explore the relationship among these
      three pathways and grade of IVD degeneration (IVDD). IVDs were collected from
      patients with lumbar fracture, vertebral tumor, disc herniation or
      spondylolisthesis. IVDs were distinguished by MRI and histomorphological
      examination, cell apoptosis was detected by TUNEL staining. Biomarkers of these
      three apoptosis pathways were detected by RT-PCR and Western blot. Furthermore,
      the correlation between apoptosis pathways biomarkers and disc pathology were
      analyzed. Nucleus pulposus cell density decreased with degeneration process, and
      increased apoptotic ratio. ER pathway was predominant in mild stage of IVDD
      (GRP78, GADD153 upregulation and caspase-4 activation), death receptor pathway
      was predominant in mild and moderate stages (Fas, FasL up-regulation and caspase
      8 activation) and mitochondrial pathway was predominant in moderate and severe
      stages (Bcl-2 down-regulation, Bax up-regulation, cytochrome-c accumulation in
      cytoplasm and caspase-9 activation). There were significant differences in the
      expressions of Fas, FasL, Bax, GADD153, cytochrome-c and cleaved caspase-8/9/3
      between contained and non-contained discs. In conclusion, apoptosis occurs via
      these three apoptosis pathways together in IVDD. ER pathway plays a more critical
      role in the mild compared to moderate and severe stages, death receptor pathway
      in mild and moderate, and mitochondrial pathway in moderate and severe stages of
      IVDD. Disc cells apoptosis may progress rapidly after herniation, and may depend
      on the type of herniation.

PMID- 21879323
TI  - Comparative analysis of evolutionary dynamics of genes encoding leucine-rich
      repeat receptor-like kinase between rice and Arabidopsis.
AB  - The leucine-rich repeat (LRR) receptor kinase (RLK) proteins constitute a large
      superfamily in the plant genome, and carry out key functions in a variety of
      biological pathways. In an effort to determine the evolutionary fate of members
      of a large gene family such as plant LRR RLK proteins we conducted in silico
      analysis using complete genome sequencing datasets, genome-wide transcriptome
      databases, and bioinformatics tools. A total of 292 and 165 LRR RLK genes were
      retrieved from the rice and Arabidopsis genomes, respectively, formed by diverse
      duplication events for gene expansion. The phylogenic analyses of the LRR RLK
      genes suggested combinations of LRR domains and RLK domains in the ancient plant
      genome prior to the divergence of rice and Arabidopsis, followed by massive
      independent expansions during speciation. The somewhat high frequencies (50-73%)
      of expressional divergence of members of duplicate gene pairs formed by
      whole/segmental genome duplication (W/SGD) and tandem duplication (TD) events of
      Arabidopsis and TD events of rice support the idea of their functional diversity
      for gene retention. By contrast, a relatively low degree (at least 20%) of
      members of rice LRR RLK gene pairs formed by W/SGD appear to be divergent in
      expression following the duplication event. At least 7 pairs of co-expressed gene
      clusters, including each of the tentative orthologous LRR RLK genes between rice
      and Arabidopsis, were enriched to an orthologous set between members of each of
      the pairs as compared to those of the random pairs, suggesting some degree of
      functional conservation of individual genes. These results may shed some light on
      the crucial functions of the plant LRR RLK genes with regard to a variety of
      biological processes.

PMID- 21879324
TI  - Intraarticular epidermal cyst of knee.

PMID- 21879325
TI  - Hematoma of the ligamentum flavum in the thoracic spine: report of two cases and
      possible role of the transforming growth factor beta-vascular endothelial growth
      factor signaling axis in its pathogenesis.

PMID- 21879327
TI  - Parkinson's disease showing progressive conduction aphasia.
AB  - Patients with Parkinson's disease (PD) may develop progressive dementia late in
      their clinical course. Dementia in PD is mostly related to neuropathological
      findings of extensive Lewy bodies (LBs), with or without the coexistence of
      Alzheimer's disease (AD) pathology. Aphasia has been reported in patients with LB
      diseases with AD pathology; however, there have been no reports of typical PD
      patients developing progressive aphasia during their clinical course. We describe
      a female PD patient who later developed progressive conduction aphasia
      characterized by phonemic paraphasia and disturbance in repetition of short
      sentences without disturbance in writing or auditory comprehension. No episodes
      of fluctuations of attention, memory complaints, or planning errors were
      observed. She experienced episodes of visual hallucination. Her low scores on the
      Mini-Mental State Examination suggested impairment of orientation and attention,
      and her scores on Raven's Coloured Progressive Matrices test indicated impaired
      visuospatial functions. However, her cognitive deficits were not sufficiently
      severe to impair her daily life. Brain magnetic resonance images revealed atrophy
      of the left superior temporal gyrus and widening of the left sylvian fissure.
      [(18)F]-fluorodeoxyglucose positron emission tomography revealed glucose
      hypometabolism in the left cerebral hemisphere. These findings may be related to
      conduction aphasia. During the progression of PD lesions, the brainstem LB is
      assumed to take an upward course, extend to the limbic system, and then extend to
      the neocortex. Conduction aphasia observed in our patient may be associated with
      an unusual progression of the LB pathology from the brainstem to the left
      temporoparietal lobe.

PMID- 21879328
TI  - Treatment for Chiari 1 malformation (CIM): analysis of a pediatric surgical
      series.
AB  - Children may present a peculiar picture of CIM, as syncopes and acute
      paraparesis. In a series of 99 children operated for CIM at FINCB there were no
      major surgical morbidity nor mortality. The preoperative symptoms improved more
      in this pediatric series than in the adult cases treated at the same institution
      in the same period; a reason could be the shorter duration of symptoms and
      another the children plasticity. An untreated nonsyndromic craniosynostosis was
      present in 10 cases. In our hands, the results of the limited extradural
      decompression were poor. In some CIM associated with psychiatric symptoms an
      unexpected improvement was observed after tonsilar resection. The associated
      Syringomyelia reduced in more than 80% of children and disappeared in a
      significant number. The rare associated tethered cord (5%) needed a double
      treatment, detethering by itself being insufficient to treat also tonsillar
      descent. The clinical symptoms are often more serious in children than in the
      adults, but the results of surgery, especially on the syrinx, are better.

PMID- 21879329
TI  - Crimp frequency is strongly correlated to myofibroblast density in the human
      anterior cruciate ligament and its autologous tendon grafts.
AB  - PURPOSE: Collagen crimp is essential for maintaining viscoelastic properties of
      normal ligament and tendon tissue. The actin isoform alpha-smooth muscle actin
      (ASMA) has been identified in fibroblastic cells of these tissues. These highly
      differentiated cells, so-called myofibroblasts may transmit tensile forces to the
      extracellular matrix, thus it has been suggested that they are responsible for
      the wrinkling of the extracellular matrix and the formation of crimp. During
      anterior cruciate ligament (ACL) graft remodeling, crimp formation plays an
      integral role. Thus, it was our purpose to determine the relationship between
      myofibroblast density and crimp frequency in human tendon graft tissue and the
      ACL. METHODS: Different tendon grafts and ACLs were harvested from young human
      multi-organ donors immediately after death. Myofibroblasts were immunostained
      with a monoclonal antibody, and histomorphometry was performed using a digital
      imaging system. Crimp length was measured, and data were correlated. RESULTS: All
      tendons and ACLs showed a significant correlation of myofibroblast density and
      crimp frequency (R(2) 0.81-0.43). The strongest correlation was found for the
      patellar tendon, the poorest for the gracilis tendon. There is also evidence that
      the phenotype respectively the shape of myofibroblasts might be responsible for
      different stages of crimp formation. CONCLUSION: With the present investigation,
      we found that myofibroblasts might be involved in crimp formation and should be
      viewed as an integral part of normal tendon and ligament tissue. Furthermore, the
      shape of myofibroblasts may further indicate the contractile potency of the
      extracellular matrix, thus presenting a dynamic and variable crimp rather than a
      static situation. This study is an experimental study. In terms of clinical
      relevance all the mentioned tendons can be used as auto- or allografts for ACL
      reconstruction, nevertheless their microscopic structure and cellular population
      have yet not been adequately investigated and compared.

PMID- 21879330
TI  - Expression of beta-defensin-4 in "an in vivo and ex vivo model" of human
      osteoarthritic knee meniscus.
AB  - PURPOSE: To investigate, for the first time, the expression of beta-defensins-4,
      by immunohistochemistry and western blotting, in OA meniscus versus control
      meniscus, thus providing new insights into the physiological processes of
      meniscus repairing. METHOD: beta-defensins-4 was studied in vivo, in knee
      osteoarthritic menisci obtained from 30 patients (20 men and 10 women) who
      underwent isolated arthroscopic partial medial or lateral meniscectomy, and in
      vitro on fibrochondrocyte cells from human OA knee menisci. The study was
      conducted using morphological, immunohistochemical, and Western blot analysis.
      RESULTS: The histological results demonstrated structural alterations and cracks
      of OA menisci accompanied by a very strong beta-defensin-4 immunohistochemical
      staining. The Western blot analysis confirmed also a strong expression of beta
      defensin-4 in OA fibrochondrocyte cells. CONCLUSION: The present study suggests
      an activation of beta-defensin-4 induction, in human knee meniscus induced by the
      OA inflammatory process. It may represent an endogenous antibiotic defense
      mechanism accompanied by an intrinsic effort of tissue remodeling in OA articular
      joints. In conclusion, the present paper suggests the clinical relevance of beta
      defensin-4 in the prospective of future alternative medical treatment for OA.

PMID- 21879331
TI  - Apoptosis of HL-60 leukemia cells induced by carbazole alkaloids isolated from
      Murraya euchrestifolia.
AB  - We carried out primary screening of 13 carbazole alkaloids isolated from the
      plant species Murraya euchrestifolia (Rutaceae) on cell growth inhibition of the
      human leukemia cell line HL-60. Among them, murrayafoline-A (1) and
      murrayazolinine (7) exhibited significant growth suppression due to apoptosis
      mediated by the activation of the caspase-9/caspase-3 pathway.

PMID- 21879332
TI  - Gambogenic acid-induced time- and dose-dependent growth inhibition and apoptosis
      involving Akt pathway inactivation in U251 glioblastoma cells.
AB  - Glioblastoma multiforme is the most common and aggressive type of primary brain
      tumor. Uncontrolled activation of the PI3K/Akt signaling pathway resulting from
      genetic alterations in phosphatase and tensin homolog deleted on chromosome 10
      (PTEN) and epidermal growth factor receptor (EGFR) correlates with poor prognosis
      and resistance to chemotherapy and radiotherapy of glioblastomas. In this study,
      we found that gambogenic acid (GNA), a polyprenylated xanthone isolated from the
      traditional medicine gamboge, efficiently arrested the cell cycle at the
      G(0)/G(1) phase by specifically repressing the expression of cyclin D1 and cyclin
      E, suppressed cell proliferation, colony formation and cell migration, and
      induced caspase-dependent apoptosis in U251 glioblastoma cells in a time- and
      dose-dependent manner. The pro-apoptotic effect of GNA on U251 cells was shown to
      be mediated through inactivation of the Akt pathway, because GNA efficiently
      suppressed the expression level of EGFR and reduced the phosphorylation of Akt
      (T308) and GSK3beta (S9). Furthermore, the combined treatment with LY294002, a
      specific inhibitor of the PI3K/Akt kinase pathway, and GNA showed a synergistic
      or additive effect on the growth of U251 cells. Our results showed that GNA is a
      promising therapeutic agent for glioblastomas.

PMID- 21879333
TI  - Ovarian gonadoblastoma with dysgerminoma in a 15-year-old girl with 46, XX
      karyotype: case report and review of the literature.
AB  - OBJECTIVE: To present a challenging case of hCG positivity in a young patient and
      to review similar cases reported in the literature. METHODS: Literature search of
      gonadoblastoma cases with pure 46, XX karyotype using PubMed database. RESULTS: A
      15-year-old girl with hCG positivity was investigated for the source and the
      initial diagnosis was an ectopic pregnancy. An ovarian tumor was identified after
      failed methotrexate therapy and the pathological diagnosis was gonadoblastoma
      with dysgerminoma. To the best of our knowledge, the case was unique in the
      literature for having the smallest diameter of a gonadoblastoma tumor with 46, XX
      karyotype. CONCLUSION: Differential diagnosis of perimenarcheal vaginal bleeding
      may be challenging for the clinician. Rare causes such as pregnancy both
      intrauterine and extrauterine and hormone producing tumors should be kept in
      mind.

PMID- 21879334
TI  - Risk of uterine rupture in women undergoing trial of labour with a history of
      both a caesarean section and a vaginal delivery.
AB  - PURPOSE: To determine the risk of uterine rupture for women undergoing trial of
      labour (TOL) with both a prior caesarean section (CS) and a vaginal delivery.
      METHODS: A systematic literature search was performed using keywords for CS and
      uterine rupture. The results were critically appraised and the data from relevant
      and valid articles were extracted. Odds ratios were calculated and a pooled
      estimate was determined using the Mantel-Haenszel method. RESULTS: Five studies
      were used for final analysis. Three studies showed a significant risk reduction
      for women with both a previous CS and a prior vaginal delivery (PVD) compared to
      women with a previous CS only, and two studies showed a trend towards risk
      reduction. The absolute risk of uterine rupture with a prior vaginal delivery
      varied from 0.17 to 0.46%. The overall odds ratio for PVD was 0.39 (95% CI 0.29
      0.52, P < 0.00001). CONCLUSION: Women with a history of both a CS and vaginal
      delivery are at decreased risk of uterine rupture when undergoing TOL compared
      with women who have only had a CS.

PMID- 21879335
TI  - Biomechanics of the female pelvic floor: a prospective trail of the alteration of
      force-displacement-vectors in parous and nulliparous women.
AB  - OBJECTIVE: We hypothesize that the holistic and multiplanar depiction of pelvic
      floor structures by dynamic MRI is of particular value in rendering information
      about the extent of functional changes that can lead to pelvic floor dysfunction.
      METHODS: 134 women were prospectively included for assessment of their pelvic
      floor function. RESULTS: Study groups differed significantly in the direction of
      their force-displacement-vectors. A shift from ventral to dorsal is present
      depending on parity, mode of delivery and age. Maternal age and body height
      correlated to the force-displacement-vector, whereas maternal weight did not.
      Pressing direction proved to be dependent on the inclination of the pelvis and
      the aperture of the levator hiatus while remaining independent from the aperture
      of the abdominal wall. CONCLUSION: Biomechanical data interpretation uncovered
      the pathogenetic relevance of progressive retroflection of the force-displacement
      vector. This is responsible for the onset of a vicious cycle of trauma-related
      force deflection perpetuating pelvic floor traumatization.

PMID- 21879336
TI  - Multistep regulation of protein kinase A in its localization, phosphorylation and
      binding with a regulatory subunit in fission yeast.
AB  - The cAMP-PKA is the major glucose-sensing pathway that controls sexual
      differentiation in Schizosaccharomyces pombe. Sequencing from the pka1 locus of
      recessive sam mutants, in which cells are highly inclined to sexual
      differentiation, led to the identification of mutations in the pka1 locus in sam5
      (pka1-G441E) and sam7 (pka1-G441R). Rst2 and Ste11 proteins were induced and
      localized to the nucleus of sam5 and sam7 mutants even under rich glucose
      conditions, indicating that the function of Pka1 was completely abolished by
      mutations. Pka1-G441E and Pka1-G441R mutant proteins reside in the cytoplasm,
      even under glucose-rich conditions, while wild-type Pka1 resides in the nucleus,
      indicating that the functionality of Pka1 is important for its nuclear
      localization. This is supported by the observation that the Pka1-T356A mutant,
      which partially lacks Pka1 function, was localized to both the cytoplasm and the
      nucleus, but an active phosphomimetic Pka1-T356D mutant prtotein was localized to
      the nucleus under glucose-rich conditions. In addition to the basal
      phosphorylation of Pka1 at T356, hyperphosphorylation of Pka1 was observed under
      glucose-starved conditions, and such hyperphosphorylation was not observed in
      pka1-G441E, pka1-G441R, pka1-T356A or pka1-T356D mutants. As these mutant
      proteins failed to interact with a regulatory subunit Cgs1, hyperphosphorylation
      of Pka1 mutant proteins was considered to be dependent on Cgs1 interaction.
      Consistent with a role for Cgs1 in Pka1 phosphorylation, we detected the
      formation of a Cgs1-Pka1 complex prior to Pka1 hyperphosphorylation. Together,
      these results indicate that nuclear localization of Pka1 depends on its activity
      and hyperphosphorylation of Pka1 depends on Cgs1 interaction.

PMID- 21879337
TI  - Quantitative evaluation of the tibial tunnel after anterior cruciate ligament
      reconstruction using diffusion weighted and dynamic contrast enhanced MRI: a
      follow-up feasibility study.
AB  - OBJECTIVE: The aim of the study was to evaluate the feasibility of two
      quantitative MRI methods: diffusion weighted imaging (DWI) and dynamic contrast
      enhanced imaging (DCEI), for follow-up assessment of the tibial tunnel after
      reconstruction of the anterior cruciate ligament (ACL). MATERIALS AND METHODS:
      Twenty-three patients were examined by MRI at 1 and 6 months following ACL
      reconstruction. DWI and DCEI were utilized for evaluating the region of interest
      (ROI) within the proximal part of the tibial tunnel. From the resulting apparent
      diffusion coefficient (ADC) maps, ADC values were calculated. DCEI data were used
      to extract the enhancement factor (f(enh)) and the enhancement gradient (g(enh))
      for the same ROI. RESULTS: Calculated ADC as well as the f(enh) and g(enh) had
      diminished to a statistically significant extent by 6 months after ACL
      reconstruction. The average ADC value diminished from 1.48 (10(-3) mm(2)/s) at 1
      month to 1.30 (10(-3) mm(2)/s) at 6 months after reconstruction. The average
      f(enh) value decreased from 1.21 at 1 month to 0.50 at 6 months and the average
      g(enh) value decreased from 2.01%/s to 1.15%/s at 6 months, respectively.
      CONCLUSION: The study proved feasibility of DWI and DCEI for quantitative
      assessment of the tibial tunnel at 1 and 6 months after ACL reconstruction. Both
      methods have the potential for use as an additional tool in the evaluation of new
      methods of ACL reconstruction. To our knowledge, this is the first time
      quantitative MRI has been used in the follow-up to the ACL graft healing process.

PMID- 21879338
TI  - Lumbar peritoneal shunt containing a programmable valve for intracranial
      hypertension caused by Borden type 1 dural arteriovenous fistulas.
AB  - Three male patients underwent lumbar peritoneal (LP) shunt for intracranial
      hypertension caused by intracranial Borden type 1 dural arteriovenous fistulas (D
      AVFs). Endovascular treatment was performed initially, but it was ineffective in
      all cases. Before LP shunt, the Mariotte blind spot expanded in all cases and
      severe papilledema was observed in two cases. We managed the opening pressure of
      the shunt system in accordance with patient symptoms. Mariotte blind spot
      expansion and papilledema disappeared after LP shunt. Follow-up cerebral
      angiography revealed spontaneous closure of D-AVFs in one case and aggressive
      conversion in two cases. D-AVFs were completely closed by transvenous
      embolization. Because the angioarchitecture of the fistula frequently worsens
      without deterioration of the symptom after LP shunt, follow-up angiography and
      additional treatment are important.

PMID- 21879339
TI  - Reduced aldehyde dehydrogenase activity and arginine vasopressin receptor 2
      expression in the kidneys of male TALLYHO/JngJ mice of prediabetic age.
AB  - The TALLYHO/JngJ (TH) mouse is a novel polygenic model of type 2 diabetes and
      exhibits obesity, hyperglycemia (males), hyperinsulinemia, hyperlipidemia, and
      enlarged pancreatic islets. Since the kidney is damaged by hyperglycemia in other
      animal models, the present study aimed to determine the kidney phenotype of TH
      mice using immunoblot and histological analyses of the kidneys of 6-week-old
      (prediabetic) and 16-week-old TH mice. Interestingly, even 6-week-old male TH
      mice showed significant increases in kidney weight, compared to C57BL/B6 (B6)
      mice. Cuboidal parietal epithelium was observed in the Bowman's capsule in male
      TH mice at the prediabetic age. Water accumulated inside the kidneys of male TH
      mice in an age-dependent manner, but not in B6 mice. Since Swr/J mice are
      reported to develop diabetes insipidus and share 86.8% genotype homology with TH
      mice, the expression level of arginine vasopressin receptor 2 (AVPR2), a
      candidate protein for diabetes insipidus, was examined and determined to be
      significantly reduced in the kidneys of prediabetic male TH mice, compared to B6
      mice. Aldehyde dehydrogenase (ALDH) activity in the kidneys of prediabetic male
      TH mice was significantly lower than that in age-matched male B6 mice, while
      there were no differences between female TH and B6 mice. These results suggest
      that the kidney phenotype of prediabetic TH mice occurs only in males,
      accompanied by a reduction in ALDH activity and AVPR2 expression. The kidney
      phenotype of male TH mice at a prediabetic age becomes evident before the onset
      of diabetes.

PMID- 21879340
TI  - HPV vaccination and the effect of information framing on intentions and
      behaviour: an application of the theory of planned behaviour and moral norm.
AB  - BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted infection
      (STI) known to cause cervical cancer and genital warts. However, making the
      genital warts aspect explicit may reduce HPV vaccination intention and behaviour
      due to perceived stigma associated with STIs. PURPOSE: This study investigated
      the effect of differential information framing on intention to receive the HPV
      vaccine using the Theory of Planned Behaviour (TPB) and moral norm construct.
      METHOD: Female university students were randomised to receive a fact sheet
      describing the HPV vaccine as: (1) preventing cervical cancer only (n = 81); or
      (2) preventing both cervical cancer and genital warts (n = 78). A 2-month follow
      up investigated relationships between vaccination intention and actual behaviour.
      RESULTS: No effect of information framing was detected on intention to receive
      the HPV vaccine, or vaccine uptake behaviour at 2-month follow-up. The
      traditional TPB components predicted 54% of the variance in vaccination intention
      (F (3,155) = 61.580, p < 0.001), and moral norm explained an additional 6.2%.
      Intention predicted a significant but relatively small proportion of variation
      (9.6%) in behaviour. CONCLUSION: The HPV vaccine does not seem to be associated
      with perceptions of stigma related to genital warts, and has broad acceptance
      among a female university population. This study demonstrates that TPB is suited
      to investigate HPV vaccination, and has helped clarify the role of moral norm
      within the TPB.

PMID- 21879341
TI  - Role of the neurosteroid allopregnanolone in the hyperalgesic behavior induced by
      painful nerve injury in rats.
AB  - The neurosteroid allopregnanolone (AP) influences the excitability of the central
      nervous system by acting as a positive allosteric modulator of gamma-aminobutyric
      acid type A (GABA(A)) receptors. Here, we investigated the role of AP and its
      therapeutic potential in rats that showed hyperalgesic behavior after undergoing
      spinal nerve ligation (SNL). AP levels measured in the spinal cord and brain of
      rats that underwent SNL were greater than the corresponding levels in control
      animals. More importantly, spinal AP levels in hyperalgesic rats were lower than
      those in the rats that did not develop hyperalgesia following SNL; in contrast,
      brain AP levels were comparable among these groups. No differences in serum AP
      levels were observed among the groups. In addition, intrathecal exogenous
      administration of AP showed the antihyperalgesic effects in hyperalgesic rats
      after SNL. These findings suggest that changes in spinal AP biosynthesis are
      involved in the pathogenesis of neuropathic pain following peripheral nerve
      injury, and pharmacological manipulation of this phenomenon may provide a
      potential therapeutic target for neuropathic pain.

PMID- 21879342
TI  - Determination of the full length sequence of a chicken astrovirus suggests a
      different replication mechanism.
AB  - The genomic RNA of a novel chicken astrovirus was determined. The full length
      sequence is 7520 nucleotides and encodes three open reading frames (1a, 1b, 2)
      for three proteins. The genomic organization was similar to other astroviruses
      with two exceptions. The open reading frame of the RNA-dependent RNA polymerase
      contains its own start codon which is different from other astroviruses described
      to date, providing evidence for a replication mechanism different than what has
      previously been described for astroviruses. Furthermore, the stem-loop structure
      located at the potential ribosomal frameshift signal described for other
      astroviruses has been shown to be a hairpin structure for the novel chicken
      astrovirus. Phylogenic analysis of the full length sequence revealed that this
      chicken astrovirus formed a branch independent from other astroviruses,
      indicating that this astrovirus is significantly different from astroviruses
      described to date.

PMID- 21879343
TI  - Association between frequency of drinking alcohol and chronic kidney disease in
      men.
AB  - OBJECTIVES: Chronic kidney disease (CKD) is a major public health problem.
      Epidemiological studies of the relationship between alcohol intake and CKD are
      scarce in Japan. This cross-sectional study aims to investigate the relationship
      between frequency of drinking alcohol and CKD in Japanese men. METHODS: The
      subjects were 9,196 men (mean +/- standard deviation age, 57.9 +/- 5.1 years) who
      underwent a health check-up. CKD was defined as estimated glomerular filtration
      rate <60 mL/min/1.73 m(2). Frequency of alcohol drinking was obtained from
      questionnaire and divided into five categories: nondrinkers, once or twice a
      week, three or four times a week, five or six times a week, and everyday
      drinkers. RESULTS: Multivariable-adjusted [age, body mass index, hypertension,
      diabetes, hyper-low-density lipoprotein (LDL) cholesterolemia, smoking, and
      physical activity] odds ratios and 95% confidence intervals (CIs) were calculated
      using logistic regression analysis. Compared with the results for the
      nondrinkers, the multivariable-adjusted odds ratios of CKD were as follows: 0.76
      (95% CI 0.60-0.95) for 1-2 drinks per week, 0.74 (95% CI 0.59-0.93) for 3-4
      drinks per week, 0.79 (95% CI 0.64-0.97) for 5-6 drinks per week, and 0.60 (95%
      CI 0.51-0.71) for everyday drinkers. There was a significant inverse trend across
      increasing frequency of drinking alcohol (p = 0.001 for trend). CONCLUSIONS: An
      inverse association was found between frequency of drinking alcohol and CKD in
      apparently healthy men.

PMID- 21879344
TI  - Work-related respiratory symptoms and lung function among solderers in the
      electronics industry: a meta-analysis.
AB  - OBJECTIVE: Research on the respiratory effect of exposure to solder fumes in
      electronics workers has been conducted since the 1970s, but has yielded
      inconsistent results. The aim of this meta-analysis was to clarify the potential
      association. METHODS: Effect sizes with corresponding 95% confidence intervals
      (CIs) for odds of respiratory symptoms related to soldering and spirometric
      parameters of solderers were extracted from seven studies and pooled to generate
      summary estimates and standardized mean differences in lung function measures
      between exposed persons and controls. RESULTS: Soldering was positively
      associated with wheeze after controlling for smoking (meta-odds ratio: 2.60, 95%
      CI: 1.46, 4.63) and with statistically significant reductions in forced
      expiratory volume in 1 s (FEV1) (-0.88%, 95% CI: -1.51, -0.26), forced vital
      capacity (FVC) (-0.64%, 95% CI: -1.18, -0.10), and FEV1/FVC (-0.35%, 95% CI: 
      0.65, -0.05). However, lung function parameters of solderers were within normal
      ranges [pooled mean FEV1: 97.85 (as percent of predicted), 95% CI: 94.70, 100.95,
      pooled mean FVC: 94.92 (as percent of predicted), 95% CI: 81.21, 108.64, and
      pooled mean FEV1/FVC: 86.5 (as percent), 95% CI: 78.01, 94.98]. CONCLUSIONS:
      Soldering may be a risk factor for wheeze, but may not be associated with a
      clinically significant impairment of lung function among electronics workers.

PMID- 21879345
TI  - Rapid automatic assessment of microvascular density in sidestream dark field
      images.
AB  - The purpose of this study was to develop a rapid and fully automatic method for
      the assessment of microvascular density and perfusion in sidestream dark field
      (SDF) images. We modified algorithms previously developed by our group for
      microvascular density assessment and introduced a new method for microvascular
      perfusion assessment. To validate the new algorithm for microvascular density
      assessment, we reanalyzed a selection of SDF video clips (n = 325) from a study
      in intensive care patients and compared the results to (semi-)manually found
      microvascular densities. The method for microvascular perfusion assessment
      (temporal SDF image contrast analysis, tSICA) was tested in several video
      simulations and in one high quality SDF video clip where the microcirculation was
      imaged before and during circulatory arrest in a cardiac surgery patient. We
      found that the new method for microvascular density assessment was very rapid
      (<30 s/clip) and correlated excellently with (semi-)manually measured
      microvascular density. The new method for microvascular perfusion assessment
      (tSICA) was shown to be limited by high cell densities and velocities, which
      severely impedes the applicability of this method in real SDF images. Hence, here
      we present a validated method for rapid and fully automatic assessment of
      microvascular density in SDF images. The new method was shown to be much faster
      than the conventional (semi-)manual method. Due to current SDF imaging hardware
      limitations, we were not able to automatically detect microvascular perfusion.

PMID- 21879346
TI  - P2Y1, P2Y6, and P2Y12 receptors in rat splenic sinus endothelial cells: an
      immunohistochemical and ultrastructural study.
AB  - Localization of three P2X and six P2Y receptors in sinus endothelial cells of the
      rat spleen was examined by immunofluorescent microscopy, and ultrastructural
      localization of the detected receptors was examined by immunogold electron
      microscopy. In immunofluorescent microscopy, labeling for anti-P2Y1, P2Y6, and
      P2Y12 receptors was detected in endothelial cells, but P2X1, P2X2, P2X4, P2Y2,
      P2Y4, and P2Y13 receptors was not detected. P2Y1 and P2Y12 receptors were
      prominently localized in the basal parts of endothelial cells. P2Y6 receptor was
      not only predominantly localized in the basal parts of endothelial cells, but
      also in the superficial layer. Triple immunofluorescent staining for a
      combination of two P2Y receptors and actin filaments showed that P2Y1, P2Y6, and
      P2Y12 receptors were individually localized in endothelial cells. Phospholipase C
      beta3, phospholipase C- gamma2, and inositol-1,4,5-trisphosphate receptors,
      related to the release of the intracellular Ca(2+) from the endoplasmic
      reticulum, were also predominantly localized in the basal parts of endothelial
      cells. In immunogold electron microscopy, labeling for P2Y1, P2Y6, and P2Y12
      receptors were predominantly localized in the basal part of endothelial cells
      and, in addition, in the junctional membrane, basal plasma membrane, and caveolae
      in the basal part of endothelial cells. Labeling for phospholipase C-beta3 and
      phospholipase C-gamma2 was dominantly localized in the basal parts and in close
      proximity to the plasma membranes of endothelial cells. The possible functional
      roles of these P2Y receptors in splenic sinus endothelial cells are discussed.

PMID- 21879348
TI  - Regarding "Long-term lead elimination from plasma and whole blood after
      poisoning".

PMID- 21879347
TI  - Human dental pulp stem cells demonstrate better neural and epithelial stem cell
      properties than bone marrow-derived mesenchymal stem cells.
AB  - Dental pulp stem cells (hDP-SCs) were primarily derived from pulp tissues of
      primary incisors, exfoliated deciduous and permanent third molar teeth. To
      understand the characteristics of hDP-SCs from impacted third molar,
      proliferation capacities, gene expression profiles, phenotypic, ultrastructural,
      and differentiation characteristics were analyzed in comparison with human bone
      marrow-derived mesenchymal stem cells (hBM-MSCs), extensively. hDP-SCs showed
      more developed and metabolically active cells. Contrary to hBM-MSCs, hDP-SCs
      strongly expressed both cytokeratin (CK)-18 and -19, which could involve in
      odontoblast differentiation and dentine repair. The intrinsic neuro-glia
      characteristics of hDP-MSCs were demonstrated by the expression of several
      specific transcripts and proteins of neural stem cell and neurons. These cells
      not only differentiate into adipogenic, osteogenic, and chondrogenic lineage, but
      also share some special characteristics of expressing some neural stem cell and
      epithelial markers. Under defined conditions, hDP-SCs are able to differentiate
      into both neural and vascular endothelial cells in vitro. Dental pulp might
      provide an alternative source for human MSCs. hDP-SCs with a promising
      differentiation capacity could be easily isolated, and possible clinical use
      could be developed for neurodegenerative and oral diseases in the future.

PMID- 21879349
TI  - Diallyl disulfide induces Ca2+ mobilization in human colon cancer cell line
      SW480.
AB  - Diallyl disulfide (DADS), one of the major organosulfur compounds of garlic, is
      recognized as a group of potential chemopreventive compounds. In this study, we
      examines the early signaling effects of DADS on human colorectal cancer cells
      SW480 loaded with Ca(2+)-sensitive dye fura-2. It was found that DADS caused an
      immediate and sustained rise of [Ca(2+)](i) in a concentration-dependent manner
      (EC(50) = 232 MUM). DADS also induced a [Ca(2+)](i) elevation when extracellular
      Ca(2+) was removed, but the magnitude was reduced by 45%. Depletion of
      intracellular Ca(2+) stores with 2 MUM carbonylcyanide m-chlorophenylhydrazone, a
      mitochondrial uncoupler, didn't affect DADS's effect. In Ca(2+)-free medium, the
      DADS-induced [Ca(2+)](i) rise was abolished by depleting stored Ca(2+) with 1 MUM
      thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor). DADS-caused
      [Ca(2+)](i) rise in Ca(2+)-containing medium was not affected by modulation of
      protein kinase C activity. The DADS-induced Ca(2+) influx was blocked by
      nicardipine (10 MUM). U73122, an inhibitor of phospholipase C, abolished ATP (but
      not DADS)-induced [Ca(2+)](i) rise. These findings suggest that DADS induced a
      significant rise in [Ca(2+)](i) in SW480 colon cancer cells by stimulating both
      extracellular Ca(2+) influx and thapsigargin-sensitive intracellular Ca(2+)
      release via as yet unidentified mechanisms.

PMID- 21879350
TI  - Frowning muscle activity and perception of effort during constant-workload
      cycling.
AB  - We have recently demonstrated that electromyogram (EMG) amplitude of the frowning
      muscles correlates with perception of effort during leg-extension exercise.
      However, during aerobic exercise the relationship between facial EMG and
      perception of effort has never been investigated. The aim of the present study
      was to investigate whether facial EMG reflects perception of effort also during
      constant-workload cycling. We investigated the effects of exercise duration and
      exercise intensity on facial EMG of the corrugator supercilii muscles, rating of
      perceived effort, heart rate, and blood lactate concentration. Twenty
      recreationally active male and female volunteers performed a constant-workload
      time to exhaustion test on a cycle ergometer. Participants were randomly
      allocated to the heavy-intensity [63 +/- 3% peak power output (P(peak))], or the
      severe-intensity (80 +/- 5% P(peak)) group. The results show that facial EMG can
      differentiate between two exercise intensities during constant-workload cycling.
      The effects of exercise duration are inconclusive. Facial EMG increased over time
      in the severe-intensity group, but not in the heavy-intensity group. Future
      studies testing a wider range of exercise intensities are required to establish a
      correlation between facial EMG and exercise intensity during aerobic exercise,
      and further investigations are needed to establish why there is a discrepancy
      between facial EMG and perception of effort during lower-intensity aerobic
      exercise.

PMID- 21879351
TI  - Acute metabolic responses to a 24-h ultra-marathon race in male amateur runners.
AB  - The study was conducted to evaluate the metabolic responses to a 24 h ultra
      endurance race in male runners. Paired venous and capillary blood samples from 14
      athletes (mean age 43.0 +/- 10.8 years, body weight 64.3 +/- 7.2 kg, VO(2max)
      57.8 +/- 6.1 ml kg(-1) min(-1)), taken 3 h before the run, after completing the
      marathon distance (42.195 km), after 12 h, and at the finish of the race, were
      analyzed for blood morphology, acid-base balance and electrolytes, lipid profile,
      interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and serum
      enzyme activities. Mean distance covered during the race was 168.5 +/- 23.1 km
      (range 125.2-218.5 km). Prolonged ultra-endurance exercise triggered immune and
      inflammatory responses, as evidenced by a twofold increase in total leukocyte
      count with neutrophils and monocytes as main contributors, nearly 30-fold
      increase in serum IL-6 and over 20-fold rise in hsCRP. A progressive exponential
      increase in mean creatine kinase activity up to the level 70-fold higher than the
      respective pre-race value, a several fold rise in serum activities of aspartate
      aminotransferase and alanine aminotransferase, and a fairly stable serum gamma
      glutamyl transferase level, were indicative of muscle, but not of liver damage.
      With duration of exercise, there was a progressive development of
      hyperventilation-induced hypocapnic alkalosis, and a marked alteration in
      substrate utilization towards fat oxidation to maintain blood glucose
      homeostasis. The results of this study may imply that progressive decline in
      partial CO(2) pressure (hypocapnia) that develops during prolonged exercise may
      contribute to increased interleukin-6 production.

PMID- 21879352
TI  - Effects of aerobic fitness on oxygen uptake kinetics in heavy intensity swimming.
AB  - This study aimed to characterise both the VO2 kinetics within constant heavy
      intensity swimming exercise, and to assess the relationships between VO2 kinetics
      and other parameters of aerobic fitness, in well-trained swimmers. On separate
      days, 21 male swimmers completed: (1) an incremental swimming test to determine
      their maximal oxygen uptake (VO2 max), first ventilatory threshold (VT), and the
      velocity associated with VO2max (vVO(2 max)) and (2) two square-wave transitions
      from rest to heavy-intensity exercise, to determine their VO2 kinetics. All the
      tests involved breath-by-breath analysis of freestyle swimming using a swimming
      snorkel. VO2 kinetics was modelled with two exponential functions. The mean
      values for the incremental test were 56.0 +/- 6.0 ml min(-1) kg(-1), 1.45 +/-
      0.08 m s(-1); and 42.1 +/- 5.7 ml min(-1) kg(-1) for VO2 max, vVO(2 max) and VT,
      respectively. For the square-wave transition, the time constant of the primary
      phase (sp) averaged 17.3 +/- 5.4 s and the relevant slow component (A'sc)
      averaged 4.8 +/- 2.9 ml min(-1) kg(-1) [representing 8.9% of the end-exercise VO2
      (%A'sc)]. sp was correlated with vVO(2 max) (r = -0.55, P = 0.01), but not with
      either VO2max (r = 0.05, ns) or VT (r = 0.14, ns). The %A' sc did not correlate
      with either VO2max (r = -0.14, ns) or vVO(2 max) (r = 0.06, ns), but was
      inversely related with VT (r = -0.61, P < 0.01). This study was the first to
      describe the VO2 kinetics in heavy-intensity swimming using specific swimming
      exercise and appropriate methods. As has been demonstrated in cycling, faster VO2
      kinetics allow higher aerobic power outputs to be attained. The slow component
      seems to be reduced in swimmers with higher ventilatory thresholds.

PMID- 21879353
TI  - Thioacetamide-induced fulminant hepatic failure induces cerebral mitochondrial
      dysfunction by altering the electron transport chain complexes.
AB  - Fulminant hepatic failure (FHF) is an acute form of hepatic encephalopathy
      resulting from severe inflammatory or necrotic liver damage without any
      previously established liver damage. This develops as a complication due to viral
      infections, and drug abuse. FHF also occurs in acute disorders like Reye's
      syndrome. Although the exact mechanisms in the etiology of FHF are not
      understood, elevated levels of brain ammonia have been consistently reported.
      Such increased ammonia levels are suggested to alter neurotransmission signals
      and impair cerebral energy metabolism due to mitochondrial dysfunctions. In the
      present study we have examined the role of cerebral electron transport chain
      complexes, including complex I, II, III IV, and pyruvate dehydrogenase in the non
      synaptic mitochondria isolated from the cortex of the thioacetamide-induced FHF
      rats. Further, we have examined if the structure of mitochondria is altered. The
      results of the current study demonstrated a decrease in the activity of the
      complex I by 31 and 48% at 18 and 24 h respectively after the thioacetamide
      injection. Similarly, the activity of electron transport chain complex III was
      inhibited by 35 and 52% respectively, at 18 and 24 h, respectively. The complex
      II and complex IV, on the other hand, revealed unaltered activity. Further the
      activity of pyruvate dehydrogenase at 18 and 24 h after the induction of FHF was
      inhibited by 29 and 43%, respectively. Our results also suggest mitochondrial
      swelling in FHF induced rats. The inhibition of the respiratory complexes III and
      I and pyruvate dehydrogenase might lead to the increased production of free
      radical resulting in oxidative stress and cerebral energy disturbances thereby
      leading to mitochondrial swelling and further contributing to the pathogenesis of
      FHF.

PMID- 21879354
TI  - How the motor system handles nouns: a behavioral study.
AB  - It is an open question whether the motor system is involved during understanding
      of concrete nouns, as it is for concrete verbs. To clarify this issue, we carried
      out a behavioral experiment using a go-no go paradigm with an early and delayed
      go-signal delivery. Italian nouns referring to concrete objects (hand-related or
      foot-related) and abstract entities served as stimuli. Right-handed participants
      read the stimuli and responded when the presented word was concrete using the
      left or right hand. At the early go-signal, slower right-hand responses were
      found for hand-related nouns compared to foot-related nouns. The opposite pattern
      was found for the left hand. These findings demonstrate an early lateralized
      modulation of the motor system during noun processing, most likely crucial for
      noun comprehension.

PMID- 21879355
TI  - Scale-down assessment of the sensitivity of Yarrowia lipolytica to oxygen
      transfer and foam management in bioreactors: investigation of the underlying
      physiological mechanisms.
AB  - A scale-down investigation of the impact of local dissolved oxygen limitation on
      lipase production by Y. lipolytica has been performed. One of the major issues
      encountered during this kind of process is foam formation, requiring a reduction
      of the overall oxygen transfer efficiency of the system in order to keep antifoam
      consumption to a reasonable level. A regulation strategy involving oxygen
      enrichment of the air flow through the reactor has allowed this issue to be
      partly overcome. For a second time, the scale dependency of the process operated
      with air enrichment has been investigated by a combination of scale-down and
      pilot-scale cultivation tests. The scale-down apparatus considered in this work
      comprised a well-mixed part connected to a plug-flow part subjected to dissolved
      oxygen limitation. Surprisingly, foaming intensity was greatly reduced in the
      case of the test performed in scale-down reactors (SDRs) while maintaining the
      same stirring and aeration intensities in the stirred part of the reactor. For
      mean residence time of 100 s in the recycle loop of the reactor, foam formation
      was significantly reduced while cell growth and lipase production were both
      unaltered. When the residence time in the recycle loop was raised to 200 s, the
      foam phenomena was also reduced, but the lipase yield was altered as well as lip2
      gene transcription and translation as shown by real-time quantitative polymerase
      chain reaction (RT-qPCR) and reporter gene activity, respectively. Our results
      clearly show the importance of primarily taking into account cell physiology for
      the scaling-up procedure.

PMID- 21879356
TI  - Encapsulation of R. planticola Rs-2 from alginate-starch-bentonite and its
      controlled release and swelling behavior under simulated soil conditions.
AB  - The plant growth-promoting bacteria (PGPR) Raoultella planticola Rs-2 was
      encapsulated with the various blends of alginate, starch, and bentonite for
      development of controlled-release formulations. The stability and release
      characteristics of these different capsule formulations were evaluated. The
      entrapment efficiency of Rs-2 in the beads (capsules) was more than 99%. The
      diameter of dry beads ranged from 0.98 to 1.41 mm. The bacteria release
      efficiency, swelling ratio, and biodegradability of the different bead
      formulations were enhanced by increasing the starch or alginate contents, but
      were impeded by higher bentonite content. The release kinetics of viable cells
      from capsules and the swelling ratio of capsules were studied in simulated soil
      media of varying temperature, moisture, pH, and salt content. The release of
      loaded Rs-2 cells and swelling of capsules are greatly affected by moisture,
      temperature, pH and salt content of the release medium. The release of viable Rs
      2 cells from capsules was positively associated with the swelling properties of
      the capsules. The release of Rs-2 cells occurred through a Case II diffusion
      mechanism. In summary, this work indicates that alginate-starch-bentonite blends
      are a viable option for the development of efficient controlled-release
      formulations of Rs-2 biofertilizer, and which could have a promising application
      in natural field conditions.

PMID- 21879357
TI  - Constitutional moments in governing science and technology.
AB  - Scholars in science and technology studies (STS) have recently been called upon
      to advise governments on the design of procedures for public engagement. Any such
      instrumental function should be carried out consistently with STS's interpretive
      and normative obligations as a social science discipline. This article
      illustrates how such threefold integration can be achieved by reviewing current
      US participatory politics against a 70-year backdrop of tacit constitutional
      developments in governing science and technology. Two broad cycles of
      constitutional adjustment are discerned: the first enlarging the scope of state
      action as well as public participation, with liberalized rules of access and
      sympathetic judicial review; the second cutting back on the role of the state,
      fostering the rise of an academic-industrial complex for technology transfer, and
      privatizing value debates through increasing delegation to professional
      ethicists. New rules for public engagement in the United Sates should take
      account of these historical developments and seek to counteract some of the anti
      democratic tendencies observable in recent decades.

PMID- 21879359
TI  - Ob/ob serum promotes a mesenchymal cell phenotype in B16BL6 melanoma cells.
AB  - In 2009, malignant melanoma was responsible for approximately 9,000 deaths in the
      US. These deaths are often associated with aggressive metastasis to secondary
      sites such as the lungs. Epidemiological and animal studies suggest that obesity
      is a risk factor for melanoma. Others have shown that B16BL6 melanoma cells
      metastasize more aggressively in obese ob/ob than in lean mice. However, the
      mechanism by which obesity promotes B16BL6 melanoma metastasis in ob/ob mice has
      not been identified. In the present study, we used serum obtained from control
      and ob/ob leptin-deficient obese mice to determine if obese serum increases the
      aggressive phenotype of melanoma cells. Results showed that ob/ob serum has
      higher levels of resistin, insulin, tPAI1, IL-6, TNF-alpha, and MCP-1 compared to
      control serum. We showed that ob/ob serum increases the invasive ability of
      B16BL6 melanomas. To further determine the mechanism by which ob/ob serum
      increases the invasive ability of melanomas, we determined the effect of ob/ob
      and control serum on genes associated with the epithelial-to-mesenchymal
      transition (EMT). Cancer cells with a mesenchymal phenotype have a higher
      metastatic ability. Snai1 and Twist are genes that are strongly associated with
      EMT and metastasis of melanomas. Our results showed that ob/ob serum increases
      the expression of Snai1 and Twist. Moreover, ob/ob serum increased matrix
      metalloproteast 9 (MMP9) activity and decreased the expression of E-cadherin and
      the metastasis suppressor gene Kiss1. In summary, results suggest that obesity
      may increase the metastatic ability of melanoma by promoting a mesenchymal cell
      phenotype.

PMID- 21879358
TI  - Molecular identification of arsenic-resistant estuarine bacteria and
      characterization of their ars genotype.
AB  - In the present study, 44 arsenic-resistant bacteria were isolated through serial
      dilutions on agar plate with concentrations >=0.05 mM of sodium arsenite and >=10
      mM of sodium arsenate from Mandovi and Zuari--estuarine water systems. The ars
      genotype characterization in 36 bacterial isolates (resistant to 100 mM of sodium
      arsenate) revealed that only 17 isolates harboured the arsA (ATPase), B (arsenite
      permease) and C (arsenate reductase) genes on the plasmid DNA. The arsA, B and C
      genes were individually detected using PCR in 16, 9 and 13 bacterial isolates
      respectively. Molecular identification of the 17 isolates bearing the ars
      genotype was carried using 16S rDNA sequencing. A 1300 bp full length arsB gene
      encoding arsenite efflux pump and a 409 bp fragment of arsC gene coding for
      arsenate reductase were isolated from the genera Halomonas and Acinetobacter.
      Phylogenetic analysis of arsB and arsC genes indicated their close genetic
      relationship with plasmid borne ars genes of E. coli and arsenate reductase of
      plant origin. The putative arsenate reductase gene isolated from Acinetobacter
      species complemented arsenate resistance in E. coli WC3110 and JM109 validating
      its function. This study dealing with isolation of native arsenic-resistant
      bacteria and characterization of their ars genes might be useful to develop
      efficient arsenic detoxification strategies for arsenic contaminated aquifers.

PMID- 21879360
TI  - The neuropsychological underpinnings to psychopathic personality traits in a
      nationally representative and longitudinal sample.
AB  - Although psychopathy is a major area of research in psychology and criminology,
      much remains unknown about its etiological underpinnings. Drawing on data from
      the National Longitudinal Study of Adolescent Health, the current study explored
      the association between neuropsychological deficits and psychopathic personality
      traits and produced three key findings. First, four neuropsychological deficits
      measures were consistently related to the measure of psychopathic personality
      traits both longitudinally and cross-sectionally. Second, neuropsychological
      deficits measures predicted variation in psychopathic personality traits for both
      males and females and the magnitude of the association between neuropsychological
      deficits and psychopathic personality traits did not vary as a function of
      gender. Third, parental socialization measures had relatively small and
      inconsistent effects on psychopathic personality traits. Suggestions for future
      research are offered.

PMID- 21879362
TI  - [Imaging in carcinoma of the upper respiratory tract. TNM classification of
      neoplastic lesions].
AB  - Computer tomography (CT) and magnetic resonance (MRI) imaging are instrumental in
      cancer staging in carcinoma of the upper respiratory tract in that they are able
      to identify local spread and tumor invasion, which can often be only
      insufficiently evaluated by clinical and endoscopic examination alone. These
      additional radiologic findings, in conjunction with the clinical examination, aid
      in choosing the most appropriate therapeutic approach. The evaluation of CT and
      MRI findings is challenging due to the complex anatomy of the head and neck area.
      This article reviews the most important anatomical structures for the evaluation
      of cancer invasion and therapeutic decision-making.

PMID- 21879363
TI  - [Compatibility of family and medical profession].
AB  - The compatibility of family and profession is especially difficult for employees
      in medical professions because of shift work and overtime. It seems that in the
      future women are going to represent the majority of medical professionals. Hence,
      with the manifest lack of physicians social aspects will also play a bigger role
      in the choice of the place of employment. In most families the classic role model
      prevails although women are well educated and men also set a high value on the
      compatibility of family and profession and would like to take parental leave and
      work in flexible working hours. This represents a chance, especially for
      radiology.

PMID- 21879361
TI  - The roles of integrins in mediating the effects of mechanical force and growth
      factors on blood vessels in hypertension.
AB  - Hypertension is characterized by a sustained increase in vasoconstriction and
      attenuated vasodilation in the face of elevated mechanical stress in the blood
      vessel wall. To adapt to the increased stress, the vascular smooth muscle cell
      and its surrounding environment undergo structural and functional changes known
      as vascular remodeling. Multiple mechanisms underlie the remodeling process,
      including increased expression of humoral factors and their receptors as well as
      adhesion molecules and their receptors, all of which appear to collaborate and
      interact in the response to pressure elevation. In this review, we focus on the
      interactions between integrin signaling pathways and the activation of growth
      factor receptors in the response to the increased mechanical stress experienced
      by blood vessels in hypertension.

PMID- 21879364
TI  - [Practical implementation of a quality management system in a radiological
      department].
AB  - This article describes the architecture of a project aiming to implement a DIN EN
      ISO 9001 quality management system in a radiological department. It is intended
      to be a practical guide to demonstrate each step of the project leading to
      certification of the system. In a planning phase resources for the implementation
      of the project have to be identified and a quality management (QM) group as core
      team has to be formed. In the first project phase all available documents have to
      be checked and compiled in the QM manual. Moreover all relevant processes of the
      department have to be described in so-called process descriptions. In a second
      step responsibilities for the project are identified. Customer and employee
      surveys have to be carried out and a nonconformity management system has to be
      implemented. In this phase internal audits are also needed to check the new QM
      system, which is finally tested in the external certification audit with
      reference to its conformity with the standards.

PMID- 21879365
TI  - The involvement of the HO-1 pathway in the anti-inflammatory action of a sulfated
      polysaccharide isolated from the red seaweed Gracilaria birdiae.
AB  - OBJECTIVES: The aim of this study was to investigate the involvement of the
      hemoxigenase-1 (HO-1) pathway in the anti-inflammatory action of a sulfated
      polysaccharide from the red seaweed Gracilaria birdiae (SP-Gb). METHODS: SP-Gb
      (5, 10 and 20 mg/kg) was administered to Wistar rats in a peritonitis model using
      carrageenan or a paw edema model using carrageenan or dextran. To analyze the
      involvement of HO-1 in the anti-inflammatory activity of SP-Gb, the animals were
      pretreated subcutaneously with a specific HO-1 inhibitor (ZnPP IX). To evaluate
      the systemic effects, SP-Gb (10 mg/kg) was administered to mice intraperitoneally
      before waiting for 48 h or for 14 days. RESULTS: SP-Gb (10 mg/kg) caused an anti
      inflammatory effect that was evidenced by a decrease in leukocytes in the
      peritoneal cavity. SP-Gb also reduced the paw edema induced by carrageenan and
      inhibited the paw edema induced by dextran in the first half-hour. After being
      inhibited by ZnPP IX, the anti-inflammatory effect of SP-Gb on carrageenan
      induced rat paw edema was not observed. SP-Gb did not cause mortality or
      significant changes in the biochemical, hematological and histopathological
      parameters. CONCLUSION: SP-Gb may be used as a tool for further investigations
      into the inflammatory processes associated with the hemoxigenase-1 pathway.

PMID- 21879366
TI  - [Sheared catheter in regional anaesthesia : causes and follow-up of an axiallary
      plexus catheter].
AB  - In the past years intoxication with local anesthetics, damage to nerves, vessels
      and other accompanying structures as well as infectiological events have been
      discussed more and more as complications accompanying peripheral nerve blocks
      (PNB). The following case report highlights a complication which seems to rarely
      occur and deals with a sheared continuous PNB, where a fragment of the catheter
      remained in the patient. The possible causes for the damage are discussed and
      recommendations on the clinical management of such a case are made.

PMID- 21879367
TI  - N2 fixation estimates in real-time by cavity ring-down laser absorption
      spectroscopy.
AB  - The most common currency for estimating N(2) fixation is acetylene reduction to
      ethylene. Real-time estimates of nitrogen fixation are needed to close the global
      nitrogen budget and these remain a critical gap in both laboratory and field
      experiments. We present a new method for continuous real-time measurements of
      ethylene production: Acetylene Reduction Assays by Cavity ring-down laser
      Absorption Spectroscopy (ARACAS). In ARACAS, air in the headspace of an
      incubation chamber is circulated with a diaphragm pump through a cavity ring-down
      ethylene spectrometer and back to the incubation chamber. This paper describes
      the new approach and its benefits compared to the conventional detection of
      ethylene by flame ionization detector gas chromatography. First, the detection of
      acetylene reduction to ethylene is non-intrusive and chemically non-destructive,
      allowing for real-time measurements of nitrogenase activity. Second, the
      measurements are made instantaneously and continuously at ppb levels, allowing
      for observation of real-time kinetics on time intervals as short as a few
      seconds. Third, the instrument can be automated for long time periods of
      measurement. Finally, the technique will be widely accessible by the research
      community as it can be readily adapted to most existing acetylene reduction
      protocols and is based on a modestly priced, commercially available instrument.
      We illustrate its use for measuring N(2) fixation using two species, the
      diazotrophic bacterium Azotobacter vinelandii and the lichen Peltigera
      praetextata. We also discuss potential limitations of the approach, primarily the
      implications of leaks in the analyzer, as well as future improvements.

PMID- 21879368
TI  - Geriatric syndromes in older homeless adults.
AB  - BACKGROUND: The average age of the US homeless population is increasing. Little
      is known about the prevalence of geriatric syndromes in older homeless adults.
      OBJECTIVE: To determine the prevalence of common geriatric syndromes in a sample
      of older homeless adults, and to compare these prevalences to those reported in
      the general older population. DESIGN: Cross-sectional. PARTICIPANTS: Two hundred
      and forty-seven homeless adults aged 50-69 recruited from eight homeless shelters
      in Boston, MA. MAIN MEASURES: Interviews and examinations for geriatric
      syndromes, including functional impairment, cognitive impairment, frailty,
      depression, hearing impairment, visual impairment, and urinary incontinence. The
      prevalences of these syndromes in the homeless cohort were compared to those
      reported in three population-based cohorts. KEY RESULTS: The mean age of the
      homeless cohort was 56.0 years, and 19.8% were women. Thirty percent of subjects
      reported difficulty performing at least one activity of daily living, and 53.2%
      fell in the prior year. Cognitive impairment, defined as a Mini-Mental State
      Examination score <24, was present in 24.3% of participants; impaired executive
      function, defined as a Trail Making Test Part B duration >1.5 standard deviations
      above population-based norms, was present in 28.3% of participants. Sixteen
      percent of subjects met criteria for frailty, and 39.8% had major depression,
      defined as a score >=10 on the Patient Health Questionnaire 9. Self-reported
      hearing and visual impairment was present among 29.7% and 30.0% of subjects,
      respectively. Urinary incontinence was reported by 49.8% of subjects. After
      multivariate adjustment for demographic characteristics, homeless adults were
      more likely to have functional impairment, frailty, depression, visual impairment
      and urinary incontinence compared to three population-based cohorts of older
      persons. CONCLUSIONS: Geriatric syndromes that are potentially amenable to
      treatment are common in older homeless adults, and are experienced at higher
      rates than in the general older population.

PMID- 21879369
TI  - The importance of social ties in sustaining medication adherence in resource
      limited settings.

PMID- 21879370
TI  - Update in perioperative medicine 2011.

PMID- 21879371
TI  - Overcoming the rigors of Klebsiella pneumoniae.

PMID- 21879372
TI  - The impact of postgraduate training on USMLE(r) step 3(r) and its computer-based
      case simulation component.
AB  - BACKGROUND: The United States Medical Licensing Examination(r) (USMLE(r)) Step
      3(r) examination is a computer-based examination composed of multiple choice
      questions (MCQ) and computer-based case simulations (CCS). The CCS portion of
      Step 3 is unique in that examinees are exposed to interactive patient-care
      simulations. OBJECTIVE: The purpose of the following study is to investigate
      whether the type and length of examinees' postgraduate training impacts
      performance on the CCS component of Step 3, consistent with previous research on
      overall Step 3 performance. DESIGN: Retrospective cohort study PARTICIPANTS:
      Medical school graduates from U.S. and Canadian institutions completing Step 3
      for the first time between March 2007 and December 2009 (n = 40,588). METHODS:
      Post-graduate training was classified as either broadly focused for general areas
      of medicine (e.g. pediatrics) or narrowly focused for specific areas of medicine
      (e.g. radiology). A three-way between-subjects MANOVA was utilized to test for
      main and interaction effects on Step 3 and CCS scores between the demographic
      characteristics of the sample and type of residency. Additionally, to examine the
      impact of postgraduate training, CCS scores were regressed on Step 1 and Step 2
      Clinical Knowledge (CK) scores. Residuals from the resulting regressions were
      plotted. RESULTS: There was a significant difference in CCS scores between
      broadly focused (MU = 216, sigma = 17) and narrowly focused (MU=211, sigma = 16)
      residencies (p < 0.001). Examinees in broadly focused residencies performed
      better overall and as length of training increased, compared to examinees in
      narrowly focused residencies. Predictors of Step 1 and Step 2 CK explained 55% of
      overall Step 3 variability and 9% of CCS score variability. CONCLUSIONS: Factors
      influencing performance on the CCS component may be similar to those affecting
      Step 3 overall. Findings are supportive of the validity of the Step 3 program and
      may be useful to program directors and residents in considering readiness to take
      this examination.

PMID- 21879373
TI  - Against all odds.

PMID- 21879374
TI  - Characteristics of patients with primary non-adherence to medications for
      hypertension, diabetes, and lipid disorders.
AB  - BACKGROUND: Information comparing characteristics of patients who do and do not
      pick up their prescriptions is sparse, in part because adherence measured using
      pharmacy claims databases does not include information on patients who never pick
      up their first prescription, that is, patients with primary non-adherence.
      Electronic health record medication order entry enhances the potential to
      identify patients with primary non-adherence, and in organizations with
      medication order entry and pharmacy information systems, orders can be linked to
      dispensings to identify primarily non-adherent patients. OBJECTIVE: This study
      aims to use database information from an integrated system to compare patient,
      prescriber, and payment characteristics of patients with primary non-adherence
      and patients with ongoing dispensings of newly initiated medications for
      hypertension, diabetes, and/or hyperlipidemia. DESIGN: This is a retrospective
      observational cohort study. PARTICIPANTS (OR PATIENTS OR SUBJECTS): Participants
      of this study include patients with a newly initiated order for an
      antihypertensive, antidiabetic, and/or antihyperlipidemic within an 18-month
      period. MAIN MEASURES: Proportion of patients with primary non-adherence overall
      and by therapeutic class subgroup. Multivariable logistic regression modeling was
      used to investigate characteristics associated with primary non-adherence
      relative to ongoing dispensings. KEY RESULTS: The proportion of primarily non
      adherent patients varied by therapeutic class, including 7% of patients ordered
      an antihypertensive, 11% ordered an antidiabetic, 13% ordered an
      antihyperlipidemic, and 5% ordered medications from more than one of these
      therapeutic classes within the study period. Characteristics of patients with
      primary non-adherence varied across therapeutic classes, but these
      characteristics had poor ability to explain or predict primary non-adherence
      (models c-statistics = 0.61-0.63). CONCLUSIONS: Primary non-adherence varies by
      therapeutic class. Healthcare delivery systems should pursue linking medication
      orders with dispensings to identify primarily non-adherent patients. We encourage
      conduct of research to determine interventions successful at decreasing primary
      non-adherence, as characteristics available from databases provide little
      assistance in predicting primary non-adherence.

PMID- 21879375
TI  - Case report of a patient with osteopoikilosis.
AB  - Osteopoikilosis (OPK) is an uncommon osteosclerotic dysplasia. There is no exact
      evidence of its etiology and pathogenesis. Usually, it is an asymptomatic
      disease, and the diagnosis is made incidentally from radiographs, which show
      multiple, small, well-defined, variably shaped and widely distributed sclerotic
      areas over the skeleton. In this study, we report a 54-year-old man who suffers
      from back and leg pain and was diagnosed OPK by radiologically and review
      literature.

PMID- 21879376
TI  - Registry of the clinical characteristics of spondyloarthritis in a cohort of
      Egyptian population.
AB  - The aim of this study was to characterize the socioeconomic features, as well as
      disease activity and functional status, treatment use, and quality of life in a
      cohort of Egyptian population. All are measured by standard instruments. This is
      a descriptive multicenter; cross-sectional study included consecutive patients
      with spondyloarthritis (SpAs) diagnosed according to the European
      spondyloarthritis study group criteria. Four Egyptian centers participated (one
      from the Upper Egypt, one from the Delta, and two from the West Coast), all
      adopted the same criteria for patient assessment, and data were collected in the
      same data base over a 12-month duration. A total of 75 patients were included in
      the study. The series consisted of 34 ankylosing spondylitis (AS) patients (64%),
      23 patients with psoriatic arthritis (45.3%), 15 patients with Juvenile onset AS
      (18.7%), 2 patients with reactive arthritis (2.7%), and one with inflammatory
      bowel disease-related arthritis (1.3%). There was predominance of male patients
      (84%). All were Caucasians; 13% from the Upper Egypt, and 87% from the Delta and
      West coast Egypt. Their mean age was 37.44 +/- 12.8 years; mean disease duration
      was 11.85 +/- 9.27 years. Pure axial disease was reported by 24% of the patients,
      and pure peripheral involvement was observed in 4%, while the mixed pattern
      (axial, peripheral, and entheseal) was observed in 34%. Dactylitis was detected
      in 9.3%, tarsitis in 8%, and enthesitis in 29.3%. The most common extra-articular
      manifestation was anterior uveitis, reported by 5.3% of patients. Human
      leukocytic antigen B27 (HLA-B27) was positive in 58.7% of the tested patients (n
      = 29). Mean Bath Ankylosing Spondylitis Disease activity Index (BASDAI) score was
      4.16 +/- 2.12, of which 22 patients had a score more than 4; mean Bath Ankylosing
      Spondylitis Functional Index 5.12 +/- 2.40, mean BASMI 4.17 +/- 2.95, mean BAS-GI
      5.92 +/- 2.00, and mean Health assessment questionnaire 1.10 +/- 0.65. In
      addition, patients with AS showed a higher incapacity for work, felt more pain
      and presented more axial affection than others. The most utilized treatments were
      the conventional drugs including non-steroidal anti-inflammatory drugs, followed
      by sulfasalazine (50%), methotrexate (14%), and steroids (6%). Tumor necrosis
      factor-alpha inhibitors were received by 7 patients (14%), mostly in the form of
      Infliximab (85.7%) and were used by only 38.7% of patients with BASDAI of 4 or
      more. This registry provides the first clinical and demographic data of SpA
      patients in Egypt upon which a large-scale database registration can be
      initiated. The most frequently diagnosed SpA in Egyptian patients was AS, with
      mainly combined axial and peripheral involvement. The clinical spectrum of SpAs
      seen among Egyptians is similar to most other registries; however, Egyptian AS
      patients showed some differences in the clinical manifestations. The low
      frequency of HLA-B27 and the clinical variations in AS may be due to different
      genetic and/or environmental factors in Egypt.

PMID- 21879377
TI  - Evaluation of apoptosis-related gene Fas (CD95) and FasL (CD178) polymorphisms in
      Iranian rheumatoid arthritis patients.
AB  - Apoptosis signals are essential for establishing homeostasis and adequate immune
      response. Dysregulation of apoptosis-related genes in the immune system, which
      could be due to gene polymorphisms, conduct to autoimmune diseases including
      rheumatoid arthritis. In the current study, the apoptosis-related gene Fas_
      670A>G, FasL_844C>T, and FasLIVS2nt_124A>G polymorphisms were genotyped in 120
      Iranian patients with rheumatoid arthritis (RA) and 112 unrelated healthy
      controls using PCR-RFLP method. Among the 120 RA patients being heterozygous in
      the promoter region of Fas_-670A/G (OR 1.42,CI 0.92-1.52, P = 0.18) and FasL_
      844C/T (OR 1.42, CI 0.92-1.52, P = 0.18) and homozygous in the minor allele for
      FasLIVS2nt_124G/G (OR 1.43, CI 0.76-1.81, P = 0.7), the frequency of these
      polymorphisms is higher in the cases than in controls and the elevated risk of RA
      were observed when the patient compared with controls, although this is not
      statistically significant.

PMID- 21879378
TI  - Recent advances in the biodegradation of chlorothalonil.
AB  - Chlorothalonil (TPN; 2,4,5,6-tetrachloroisophthalonitrile) has been widely used
      as a broad-spectrum chlorinated aromatic fungicide and its application resulted
      in global pollution commonly detected in the diverse ecosystems. Recently,
      microbial degradation of TPN has been studied extensively as an effective and
      environmental-friendly method to reduce TPN residue levels in the environment.
      This review summarizes the current knowledge of recent developments in the
      biodegradation of TPN. Diverse pure culture strains capable of degrading TPN were
      widely distributed among Proteobacteria and several metabolic pathways of TPN
      biotransformation were discovered. The two key genes (glutathione S-transferase
      and chlorothalonil hydrolytic dehalogenase coding gene) responsible for the
      conversion of TPN and recent findings for future practical bioremediation of TPN
      contaminated ecosystem are also discussed.

PMID- 21879379
TI  - Clinical pathologic conference case 5: agranulocytosis.

PMID- 21879380
TI  - Moderating effects of aggression on the associations between social withdrawal
      subtypes and peer difficulties during early adolescence.
AB  - Recent research has revealed significant heterogeneity in the peer difficulties
      associated with social withdrawal subtypes during early adolescence, but little
      is known about possible sources of that heterogeneity. This study of 194 Indian
      young adolescents (48% female; 90% Hindu; M age= 13.35 years) evaluated whether
      the peer adversity related to self-reported social withdrawal subtypes (shyness,
      unsociability, avoidance) varied as a function of peer-nominated overt and
      relational aggression, and gender. Regression analyses revealed that overt
      aggression and gender moderated the pathways between shyness and peer exclusion
      and peer victimization such that the associations were significant and positive
      only for boys who were high and girls who were low in overt aggression. Several
      additional moderator effects were found, including results revealing that
      relational aggression (in certain cases, in conjunction with gender) moderated
      the association between: (1) avoidance and peer exclusion and peer rejection, (2)
      shyness and peer rejection, and (3) unsociability and peer victimization. For
      adolescents who were average and low in relational aggression, avoidance was
      positively related to peer rejection, and unsociability was positively related to
      peer victimization. However, only for boys who were high in relational
      aggression, avoidance was found to be positively related to peer exclusion, and
      shyness was positively related to peer rejection. The findings highlight the
      importance of considering additional individual risk factors in studies of social
      withdrawal subtypes and point to important differences for young adolescent
      withdrawn boys and girls.

PMID- 21879381
TI  - Growing up too soon? Parentification among immigrant and native adolescents in
      Germany.
AB  - Parentification (adolescents' adoption of adult family roles by providing
      instrumental or emotional support for their parents) is assumed to be higher in
      immigrant than native families. An often discussed reason for parentification is
      the adolescent-parent acculturation gap in immigrant families whereby immigrant
      adolescents acculturate faster and outperform their parents socio-culturally. The
      aim of this multi-informant, multi-group study was to investigate levels,
      predictors, and psychosocial outcomes of instrumental and emotional
      parentification. The sample comprised 197 native (adolescents: mean age 14.7
      years, 52% female) and 185 ethnic German immigrant (adolescents: mean age 15.7
      years, 60% female) mother-adolescent dyads. Results revealed higher levels of
      emotional and instrumental parentification among immigrant adolescents. Parents'
      partnership dissatisfaction predicted instrumental and emotional parentification
      only in the native German sample. Among immigrants, language brokering related to
      instrumental and emotional parentification, and a larger mother-adolescent
      acculturation gap was associated with higher levels of emotional parentification.
      The positive psychosocial outcome, self-efficacy, was predicted by instrumental
      parentification in both adolescent groups. Exhaustion, the negative outcome,
      however, was related to higher levels of instrumental and lower levels of
      emotional parentification only in the immigrant group. The results of this study
      highlight that family systems can change due to migration to another country,
      with adolescents becoming more responsible for family matters than is normative
      for their age. However, only some of these premature responsibilities carry a
      risk of maladaptation, with others seeming to provide opportunities for positive
      developmental growth.

PMID- 21879382
TI  - Involuntary craniofacial lingual movements in intensive care-acquired
      quadriplegia.
AB  - BACKGROUND: The syndrome of involuntary craniofacial lingual movements in the
      setting of acute intensive care-acquired quadriplegia (critical illness
      neuromyopathy) following sepsis-associated encephalopathy has not been previously
      described. We suggest a localization and treatment for this disabling condition.
      METHODS: Three patients (2 female) from our center were quadriplegic from
      critical illness neuromyopathy when they developed involuntary craniofacial
      lingual movements following sepsis-associated encephalopathy. RESULTS: Extensive
      investigations failed to identify an etiology for the abnormal movements.
      Movements were of large amplitude, of moderate speed, and semi-rhythmic in the
      jaw, tongue, and palate, persistent and extremely bothersome to all patients.
      Injection with Botulinum toxin type A was very beneficial. CONCLUSIONS:
      Involuntary craniofacial lingual movements in the setting of flaccid quadriplegia
      following sepsis-associated encephalopathy are consistent with focal craniofacial
      brainstem myoclonus and constitutes a new syndrome. Botulinum toxin type A
      treatment maybe helpful in treatment.

PMID- 21879385
TI  - OMIT: a domain-specific knowledge base for microRNA target prediction.
AB  - Identification and characterization of the important roles microRNAs (miRNAs)
      perform in human cancer is an increasingly active research area. Unfortunately,
      prediction of miRNA target genes remains a challenging task to cancer
      researchers. Current processes are time-consuming, error-prone, and subject to
      biologists' limited prior knowledge. Therefore, we propose a domain-specific
      knowledge base built upon Ontology for MicroRNA Targets (OMIT) to facilitate
      knowledge acquisition in miRNA target gene prediction. We describe the ontology
      design, semantic annotation and data integration, and user-friendly interface and
      conclude that the OMIT system can assist biologists in unraveling the important
      roles of miRNAs in human cancer. Thus, it will help clinicians make sound
      decisions when treating cancer patients.

PMID- 21879384
TI  - Polymorph formation and nucleation mechanism of tolfenamic acid in solution: an
      investigation of pre-nucleation solute association.
AB  - PURPOSE: Crystallization from solution involves nucleation and growth; growth
      conditions greatly influence self-association behaviors of solute molecules in
      these steps, affecting crystal packing of organic molecules. We examined the role
      of pre-nucleation association to provide insights into the mutual influence
      between molecular conformation in solution and packing in the solid state.
      METHODS: Crystallization experiments of tolfenamic acid were conducted in ethanol
      under different supersaturation conditions. UV spectroscopy was performed to
      study self-association of solute molecules in ethanol as a function of
      concentration. Intermolecular interaction energies of tolfenamic acid dimers were
      calculated with quantum mechanical methods. RESULTS: As supersaturation
      increased, growth of the most stable polymorph outpaced the metastable one,
      contradicting Ostwald's Rule of Stages. UV spectroscopy measurement suggests
      solute molecules exist as hydrogen-bonded dimers and more dimers form as total
      concentration increases. Hydrogen bonding in the most stable form is
      significantly stronger than that in the metastable form. CONCLUSIONS: With the
      fact that molecular conformation is different in the two polymorphs, as
      concentration increases, solute molecules rearrange their conformations to form
      stronger hydrogen-bonded dimers in solution, resulting in nucleation of the most
      stable form.

PMID- 21879383
TI  - White matter abnormalities and their impact on attentional performance in adult
      attention-deficit/hyperactivity disorder.
AB  - Inattention is the most important behavioral feature of adult patients with
      attention-deficit/hyperactivity disorder (ADHD). Neuroimaging studies in ADHD
      have demonstrated abnormalities primarily in the frontostriatal circuitry and
      were mostly conducted in children. We investigated white matter (WM) integrity in
      adult ADHD patients and the correlation of WM microstructure and
      neuropsychological parameters in 37 (21 men) never-medicated adult ADHD patients
      and 34 age- and gender-matched healthy controls. All subjects underwent clinical
      interviews, rating scales, and neuropsychological tests of attentional
      performance. Diffusion tensor imaging (DTI) was acquired, and 12 WM regions-of
      interest (ROIs) within the attentional network were chosen. Group differences of
      mean fractional anisotropy (FA) and mean diffusivity (MD) values were calculated
      for each ROI, and patients' DTI measures were then correlated with measures of
      attentional performance. FA values in ADHD patients were significantly reduced in
      the left inferior longitudinal fasciculus (ILF), while MD values were
      significantly increased in ADHD patients in the frontal portion of the left
      frontooccipital fasciculus (IFO). In ADHD patients, MD values were negatively
      correlated with attentional performance in the left ILF. Our findings provide
      further support for disturbed frontostriatal structural connectivity and also
      point to an involvement of the left temporal white matter with an impact on
      attentional performance.

PMID- 21879386
TI  - Delivery of brain-derived neurotrophic factor via nose-to-brain pathway.
AB  - PURPOSE: To investigate the plausibility of delivering brain-derived neurotrophic
      factor (BDNF) to brain via nose-to-brain pathway using chitosan as barrier
      modulating agent. METHODS: Effect of different viscosity grades chitosan at
      different concentrations on permeation of fluorescein isothio-cyanate dextran (FD
      40 K) across bovine olfactory mucosa was studied using Franz diffusion cells.
      Medium viscosity chitosan was used to carry out permeation studies of BDNF.
      Pharmacokinetic and pharmacodynamic studies were carried out in Sprague dawley
      rats upon intranasal/i.v administration of different formulations. RESULTS:
      Medium viscosity chitosan more efficiently enhanced permeation of FD 40 K across
      olfactory mucosa compared to other grades. In case of BDNF, medium viscosity
      chitosan (0.25% w/v) enhanced permeation ~14-fold over control (18.78 +/- 16.69
      ng/cm(2)). Brain bioavailability of rats administered intranasally with BDNF
      solution containing chitosan was significantly enhanced ~13-fold compared to rats
      administered with same concentration of BDNF solution without chitosan. In rats
      subjected to immobilization stress, BDNF solution containing chitosan
      significantly decreased immobility time. CONCLUSIONS: Intranasal formulations
      containing chitosan as barrier-modulating agent significantly enhanced brain
      bioavailability of BDNF. Delivery of BDNF was found to counteract stress-induced
      depression in rats.

PMID- 21879387
TI  - Cationic liposomal co-delivery of small interfering RNA and a MEK inhibitor for
      enhanced anticancer efficacy.
AB  - PURPOSE: To test whether co-delivery of anticancer small interfering RNA (siRNA)
      and a chemical MEK inhibitor using cationic liposomes enhances anticancer
      activity in vitro and in vivo. METHOD: MEK inhibitor PD0325901 was encapsulated
      in lipid layers of N',N''-dioleylglutamide-based cationic liposomes (DGL). Mcl1
      specific siRNA (siMcl1) was complexed to DGL or PD0325901-loaded liposomes
      (PDGL). Efficiency of cellular siRNA delivery was tested using fluorescent double
      stranded RNA. Silencing of target proteins was evaluated using Western blotting
      and real-time quantitative polymerase chain reactions. In vivo anticancer
      activity was tested using xenografted mice. RESULTS: Size and zeta potential of
      PDGL were similar to DGL. PDGL could deliver double-stranded RNA into cells with
      efficiencies comparable to DGL. Cellular co-delivery of siMcl1 and PD0325901
      reduced expression of Mcl1 and pERK1/2 proteins and more effectively reduced
      tumor cell survival than other treatments. In mice, siMcl1 and PD0325901 co
      delivered by PDGL inhibited growth of tumors 79%. Substantial apoptosis of tumor
      cells was observed following PDGL-mediated co-delivery of siMcl1, but not in
      other groups. CONCLUSIONS: PDGL-mediated co-delivery of siMcl1 and MEK inhibitor,
      PD0325901, could serve as a potential strategy for combination chemogene
      anticancer therapy.

PMID- 21879388
TI  - Comparative investigations on in vitro serum stability of polymeric micelle
      formulations.
AB  - PURPOSE: Stability of polymeric micelles upon injection is essential for a drug
      delivery system but is not fully understood. We optimized an analytical test
      allowing quantification of micellar stability in biofluids and applied it to a
      variety of block copolymer micelles with different hydrophobic block
      architechtures. METHODS: Polymeric micelles were prepared from four different
      polymers and investigated via encapsulation of two fluorescent dyes. Samples were
      incubated in human serum; changes in Foerster Resonance Energy Transfer (FRET)
      were recorded as a function of time. This fluorescence-based approach was
      supported semi-quantitatively by results from Asymmetrical Flow Field-Flow
      Fractionation (AF4). RESULTS: After incubation experiments, micellar stability
      was determined by calculation of two stability-indicating parameters: residual
      micellar fractions (RMFs) and in vitro serum half-lives. Both parameters showed
      that PEG-PVPy micelles rapidly destabilized after 3 h (RMF < 45%), whereas PEG
      PLA, PEG-PLGA and PEG-PCL micelles were far more stable (RMFs 65 to 98%).
      CONCLUSION: This FRET-based assay is a valuable tool in evaluating and screening
      serum stability of polymeric micelles and revealed low serum stability of PEG
      PVPy micelles compared to polyester-based micelles.

PMID- 21879390
TI  - Students' learning as the focus for shared involvement between universities and
      clinical practice: a didactic model for postgraduate degree projects.
AB  - In an academic programme, completion of a postgraduate degree project could be a
      significant means of promoting student learning in evidence- and experience-based
      practice. In specialist nursing education, which through the European Bologna
      process would be raised to the master's level, there is no tradition of including
      a postgraduate degree project. The aim was to develop a didactic model for
      specialist nursing students' postgraduate degree projects within the second cycle
      of higher education (master's level) and with a specific focus on nurturing
      shared involvement between universities and healthcare settings. This study
      embodies a participatory action research and theory-generating design founded on
      empirically practical try-outs. The 3-year project included five Swedish
      universities and related healthcare settings. A series of activities was
      performed and a number of data sources secured. Constant comparative analysis was
      applied. A didactic model is proposed for postgraduate degree projects in
      specialist nursing education aimed at nurturing shared involvement between
      universities and healthcare settings. The focus of the model is student learning
      in order to prepare the students for participation as specialist nurses in
      clinical knowledge development. The model is developed for the specialist nursing
      education, but it is general and could be applicable to various education
      programmes.

PMID- 21879389
TI  - MicroRNA replacement therapy for cancer.
AB  - MicroRNA are small noncoding RNAs that translationally repress their target
      messenger RNAs. Many microRNAs are expressed at reduced levels in tumors.
      microRNAs with reduced expression in cancer often regulate oncogenes, resulting
      in enhanced tumor growth. One therapeutic option is to restore microRNA levels in
      the tumor to that of the non-diseased tissue. This is possible by delivering
      microRNA to the tumor in the form of an oligonucleotide mimic or by expressing
      the microRNA in the cancer using a gene vector. This article surveys the field of
      oligonucleotide mimics and gene vector approaches to restore microRNA levels in
      tumors and reviews the literature on experimental and pre-clinical studies that
      have used these approaches to treat cancer.

PMID- 21879391
TI  - In vitro and in vivo investigation of drug-eluting implants for the treatment of
      periodontal disease.
AB  - This paper developed solvent-free drug-eluting implants for metronidazole
      delivery for the treatment of periodontal disease and investigated the
      characteristics of the drug's release from the implants, both in vitro and in
      vivo, using an HPLC assay. The metronidazole exhibited a two-stage release
      behavior in vitro with an initial burst release followed by a diffusion
      controlled release and then a secondary burst release. The accumulated drug
      release reached 100% on the 18th day, and the drug-eluting implant was totally
      dissolved on the same day. Additionally, the drug-eluting disks were implanted
      within the sub-gingival space of both lower incisors of six rabbits. The curve of
      in vivo drug release was smoother and showed a predominantly diffusion-controlled
      release. The implants were totally dissolved at 2 weeks after implantation. The
      concentration of metronidazole remained above the MIC(90) during the entire
      investigation.

PMID- 21879392
TI  - Formulation and evaluation of in situ gelling systems for intranasal
      administration of gastrodin.
AB  - Gastrodin is the major bioactive constituent of the traditional Chinese drug
      "Tianma." It is used in the treatment of some nervous system diseases and can be
      transported to the brain via intranasal administration. In the current paper, the
      development of a novel ion-activated in situ gelling system for the nasal
      delivery of gastrodin is discussed. An in situ perfusion model was used to
      determine the absorption-rate constant of gastrodin through rat nasal mucosa. The
      optimal formulation was determined by measuring the critical cation
      concentration, anti-dilution capacity, gel expansion coefficient, water-holding
      capacity, and adhesive capacity. The best formulation consisted of 10% gastrodin,
      0.5% deacetylated gellan gum as the gelatinizer, and 0.03% ethylparaben as the
      preservative. The rheological properties of gastrodin nasal in situ gels were
      also investigated. The viscosity and elasticity sharply increased at temperatures
      below 25 degrees C. When physiological concentrations of cations were added into
      the preparation, the mixture gelled into a semi-solid. The results of an
      accelerated stability test show that gastrodin nasal in situ gels can be stable
      for more than 2 years. Mucociliary toxicity was evaluated using the in situ toad
      palate model and the rat nasal mucociliary method; both models demonstrated no
      measurable ciliotoxicity. Pharmacodynamic studies suggest that similar acesodyne
      and sedative effects were induced following intranasal administration of 50 mg/kg
      gastrodin nasal in situ gels or oral administration of 100 mg/kg gastrodin
      solution. The in situ gel preparation is a safe and effective nasal delivery
      system for gastrodin.

PMID- 21879393
TI  - Brimonidine tartrate-eudragit long-acting nanoparticles: formulation,
      optimization, in vitro and in vivo evaluation.
AB  - In the present study, an effort was made to design prolonged release Eudragit
      nanoparticles of brimonidine tartrate by double emulsion-solvent evaporation
      technique for the treatment of open-angle glaucoma. The effect of various
      formulation variables like initial drug amount, lecithin proportion, phase volume
      and pH, secondary emulsifier and polymer proportion were studied. Various process
      variables like energy and duration of emulsification, lyophilization on the
      characteristics of nanoparticles and in vitro drug release profile were studied.
      The selected formulations were subjected to in vivo intraocular pressure-lowering
      efficacy studies by administering aqueous dispersion of nanoparticles into the
      lower cul de sac of glaucomatous rabbits. The prepared Eudragit-based
      nanoparticles were found to have narrow particle size range and improved drug
      loading. The investigated process and formulation variables found to have
      significant effect on the particle size, drug loading and entrapment efficiency,
      and in vitro drug release profile of nanoparticles. The selected formulations
      upon in vivo ocular irritability and tolerability tests were found to be well
      tolerated with no signs of irritation. In vivo pharmacodynamic efficacy studies
      revealed that the selected nanoparticle formulations significantly improved the
      therapy as area under the ?IOP vs. time curve [AUC((?IOP vs. t))] showed several
      fold increase in intensity and duration of intraocular pressure (IOP) decrease.
      All the selected nanoparticle formulations were found to prolong the drug release
      in vitro and prolong IOP reduction efficacy in vivo, thus rendering them as a
      potential carrier in developing improved drug delivery systems for the treatment
      of glaucoma.

PMID- 21879394
TI  - Enhanced bioavailability of atorvastatin calcium from stabilized gastric resident
      formulation.
AB  - Oral bioavailability of atorvastatin calcium (ATC) is very low (only 14%) due to
      instability and incomplete intestinal absorption and/or extensive gut wall
      extraction. When ATC is packed in the form of tablets, powders, etc., it gets
      destabilized as it is exposed to the oxidative environment, which is usually
      present during the production process, the storage of the substance, and the
      pharmaceutical formulation. Therefore, stabilized gastro-retentive floating
      tablets of ATC were prepared to enhance bioavailability. Water sorption and
      viscosity measurement studies are performed to get the best polymer matrix for
      gastro-retention. A 3(2) factorial design used to prepare optimized formulation
      of ATC. The selected excipients such as docusate sodium enhanced the stability
      and solubility of ATC in gastric media and tablet dosage form. The best
      formulation (F4) consisting of hypromellose, sodium bicarbonate, polyethylene
      oxide, docusate sodium, mannitol, crosscarmellose sodium, and magnesium stearate,
      gave floating lag time of 56 +/- 4.16 s and good matrix integrity with in vitro
      dissolution of 98.2% in 12 h. After stability studies, no significant change was
      observed in stability, solubility, floating lag time, total floating duration,
      matrix integrity, and sustained drug release rates, as confirmed by DSC and
      powder X-ray diffraction studies. In vivo pharmacokinetic study performed in
      rabbits revealed enhanced bioavailability of F4 floating tablets, about 1.6 times
      compared with that of the conventional tablet (Storvas(r) 80 mg tablet). These
      results suggest that the gastric resident formulation is a promising approach for
      the oral delivery of ATC for improving bioavailability.

PMID- 21879395
TI  - Cyberknife hypofractionated stereotactic radiosurgery (HSRS) of resection cavity
      after excision of large cerebral metastasis: efficacy and safety of an 800 cGy *
      3 daily fractions regimen.
AB  - Development of hypofractionated stereotactic radiosurgery (HSRS) has expanded the
      size of lesion that can be safely treated by focused radiation in a limited
      number of treatment sessions. However, clinical data regarding the efficacy and
      morbidity of HSRS in the treatment of cerebral metastasis is lacking. Here, we
      review our experience with CyberKnife((r)) HSRS for this indication. From 2005 to
      2010, we identified 37 patients with large (>3 cm in diameter) cerebral
      metastases resection cavity that was treated with HSRS. This constituted
      approximately 8% of all treated resection cavities. We reviewed dose regimens,
      local control, distal control, and treatment associated morbidities. Primary
      sites for the metastatic lesions included: lung (n = 10), melanoma (n = 12),
      breast (n = 9), kidney (n = 4), and colon (n = 2). All patients underwent
      resection of the cerebral metastasis and received 800 cGy * 3 daily fractions to
      the resection cavity. Of the 37 patients treated, one-year follow-up data was
      available for 35 patients. The median survival was 5.5 months. Actuarial local
      control rate at 6 months was 80%. Local failures did not correlate with prior
      WBRT, or tumor histology. Distant recurrence occurred in 7 of the 35 patients.
      Morbidities associated with HSRS totaled 9%, including radiation necrosis (n = 1,
      2.9%), prolonged steroid use (n = 1, 2.9%), and new-onset seizures (n = 1, 2.9%).
      This study demonstrates the safety and efficacy of an 800 cGy * 3 daily fractions
      CyberKnife((r)) HSRS regimen for irradiation of large resection cavity. The
      efficacy compares favorably to historical data derived from patients undergoing
      WBRT, SRS, or brachytherapy.

PMID- 21879397
TI  - How do snails meet fish? Landscape perspective needed to study parasite
      prevalence.
AB  - We echo the viewpoints presented in the recent editorials and forums in ecohealth
      in 2009 and 2010 that understanding the links between water and health using
      biogeography can provide insights into the patterns of and the processes that
      give rise to the distribution of disease prevalence. In particular, we underscore
      the need to integrate disease ecology and biogeography using landscape ecological
      approaches. We use opisthorchiasis, a major public health problem in Southeast
      Asia, to illustrate our opinions.

PMID- 21879398
TI  - Does urban sprawl impact on self-rated health and psychological distress? A
      multilevel study from Sydney, Australia.
AB  - Mental health can be influenced by a number of neighbourhood physical and social
      environmental characteristics. We aimed to determine whether urban sprawl (based
      on population density) in Sydney, Australia, is associated with self-rated health
      and psychological distress. We used a cross-sectional multilevel study design.
      Individual level data on self-rated health and psychological distress were
      obtained from the 2006 and 2007 NSW Population Health Survey. We did not find
      significant associations between urban sprawl and self-rated health and
      psychological distress after controlling for individual and area level
      covariates. However, positive neighbourhood factors were generally associated
      with better self-rated health and lower psychological distress but few of these
      associations were statistically significant.

PMID- 21879399
TI  - [Diagnostic criteria for eating disorders: what will DSM-5 feature?].
AB  - The diagnostic criteria of the classic eating disorders anorexia nervosa (AN) and
      bulimia nervosa (BN) are characterized by both a high validity and clinical
      utility. However, up to 50% of patients in specialized eating disorder centers do
      not meet the full diagnostic criteria and are relegated to the residual diagnosis
      "eating disorders not otherwise specified (EDNOS)". Eating disorders are more
      varied and variable than the ICD-10 or DSM-IV criteria suggest. This article
      describes the suggested modifications of the diagnostic criteria for eating
      disorders for the DSM-5. The DSM-5 abstains from setting a specific numerical
      standard for weight for AN and reduces the required minimum frequency for BN and
      binge eating disorder (BED) to once a week over the last 3 months. This will
      likely reduce the number of cases in the EDNOS category. In addition, the DSM-5
      provides brief descriptions of several conditions of potential clinical
      significance without providing detailed criteria in order to stimulate additional
      research.

PMID- 21879400
TI  - Dynamic contrast-enhanced magnetic resonance imaging with Gd-EOB-DTPA for the
      evaluation of liver fibrosis in chronic hepatitis patients.
AB  - OBJECTIVES: To develop a non-invasive MRI method for evaluation of liver
      fibrosis, with histological analysis as the reference standard. METHODS: The
      study protocol was approved by the Institutional Review Board for Human Studies
      of our hospital, and written informed consent was obtained from all subjects.
      Seventy-nine subjects who received dynamic contrast-enhanced MRI (DCE-MRI) with
      Gd-EOB-DTPA were divided into three subgroups according to Metavir score: no
      fibrosis (n = 30), mild fibrosis (n = 34), and advanced fibrosis (n = 15). The
      DCE-MRI parameters were measured using two models: (1) dual-input single
      compartment model for arterial blood flow (F (a)), portal venous blood flow,
      total liver blood flow, arterial fraction (ART), distribution volume, and mean
      transit time; and (2) curve analysis model for Peak, Slope, and AUC. Statistical
      analysis was performed with Student's t-test and the nonparametric Kruskal-Wallis
      test. RESULTS: Slope and AUC were two best perfusion parameters to predict the
      severity of liver fibrosis (>F2 vs. ?F2). Four significantly different variables
      were found between non-fibrotic versus mild-fibrotic subgroups: F (a), ART,
      Slope, and AUC; the best predictor for mild fibrosis was F (a) (AUROC:0.701).
      CONCLUSIONS: DCE-MRI with Gd-EOB-DTPA is a noninvasive imaging, by which multiple
      perfusion parameters can be measured to evaluate the severity of liver fibrosis.

PMID- 21879401
TI  - TRPA1-mediated accumulation of aminoglycosides in mouse cochlear outer hair
      cells.
AB  - Aminoglycoside ototoxicity involves the accumulation of antibiotic molecules in
      the inner ear hair cells and the subsequent degeneration of these cells. The
      exact route of entry of aminoglycosides into the hair cells in vivo is still
      unknown. Similar to other small organic cations, aminoglycosides could be brought
      into the cell by endocytosis or permeate through large non-selective cation
      channels, such as mechanotransduction channels or ATP-gated P2X channels. Here,
      we show that the aminoglycoside antibiotic gentamicin can enter mouse outer hair
      cells (OHCs) via TRPA1, non-selective cation channels activated by certain
      pungent compounds and by endogenous products of lipid peroxidation. Using
      conventional and perforated whole-cell patch clamp recordings, we found that
      application of TRPA1 agonists initiates inward current responses in wild-type
      OHCs, but not in OHCs of homozygous Trpa1 knockout mice. Similar responses
      consistent with the activation of non-selective cation channels were observed in
      heterologous cells transfected with mouse Trpa1. Upon brief activation with TRPA1
      agonists, Trpa1-transfected cells become loaded with fluorescent gentamicin-Texas
      Red conjugate (GTTR). This uptake was not observed in mock-transfected or non
      transfected cells. In mouse organ of Corti explants, TRPA1 activation resulted in
      the rapid entry of GTTR and another small cationic dye, FM1-43, in OHCs and some
      supporting cells, even when hair cell mechanotransduction was disrupted by pre
      incubation in calcium-free solution. This TRPA1-mediated entry of GTTR and FM1-43
      into OHCs was observed in wild-type but not in Trpa1 knockout mice and was not
      blocked by PPADS, a non-selective blocker of P2X channels. Notably, TRPA1
      channels in mouse OHCs were activated by 4-hydroxynonenal, an endogenous molecule
      that is known to be generated during episodes of oxidative stress and accumulate
      in the cochlea after noise exposure. We concluded that TRPA1 channels may provide
      a novel pathway for the entry of aminoglycosides into OHCs.

PMID- 21879402
TI  - Similar outcomes for nail versus plate fixation of three-part proximal humeral
      fractures.
AB  - BACKGROUND: There is a lack of consensus regarding optimal surgical management of
      displaced and unstable three-part proximal humeral fractures. QUESTIONS/PURPOSES:
      The objective of this prospective observational study was to compare the clinical
      and radiologic outcomes of plate versus nail fixation of three-part proximal
      humeral fractures. PATIENTS AND METHODS: Two hundred eleven patients with
      unstable three-part proximal humeral fractures were treated with ORIF using plate
      (PHILOS [proximal humeral interlocking system]/LPHP [locking proximal humerus
      plate]) or nail (PHN [proximal humeral nail]) osteosynthesis. Outcome
      measurements included pain, Constant and Murley and Neer scores, and the
      occurrence of complications at 3, 6, and 12 months postsurgery. Regression
      analysis and the likelihood ratio test were used to evaluate differences between
      the cohorts. RESULTS: Throughout the 1-year followup period the Constant and
      Murley scores improved significantly for both cohorts; there was no significant
      difference between the nail group compared with the plate group. Also, 1-year
      Neer scores were similar between the two cohorts. Patients in the PHN group
      perceived significantly less pain compared with patients in the plate fixation
      group at 3, 6 and 12 months after surgery. We observed 79 local complications in
      60 patients with no significant risk difference between the treatment groups; 35
      intraoperative complications were directly related to the initial surgical
      procedure. CONCLUSIONS: The similar 1-year outcomes for nail versus plate
      fixation of three-part proximal humeral fractures suggest that both techniques
      may be useful for internal fixation of these fractures. Many complications were
      related to incorrect surgical technique and therefore can be avoided. Advanced
      surgical skills and experience are considered to be more critical for successful
      operative treatment of three-part proximal humeral fractures than the selection
      of the implant. LEVEL OF EVIDENCE: Level II, therapeutic study (prospective
      comparative study). See the Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 21879403
TI  - Is reverse shoulder arthroplasty appropriate for the treatment of fractures in
      the older patient? Early observations.
AB  - BACKGROUND: The treatment of comminuted proximal humerus fractures in older
      patients is challenging. Variable values of functional outcomes scores, ROMs,
      patient satisfaction, and bony healing have been reported with conventional
      techniques, including open reduction and internal fixation, percutaneous pinning,
      and hemiarthroplasty. Another alternative is reverse total shoulder arthroplasty,
      although it is unclear whether this provides better ROM or function.
      QUESTIONS/PURPOSES: We (1) evaluated ROM, pain level, and American Shoulder and
      Elbow Surgeons scores of patients who had a reverse total shoulder arthroplasty
      for displaced three- and four-part proximal humerus fracture and (2) identified
      clinical and radiographic complications from the procedure. PATIENTS AND METHODS:
      We retrospectively reviewed 30 patients in three institutions who had undergone a
      primary reverse total shoulder arthroplasty for displaced three- or four-part
      proximal humerus fractures. Mean age was 77 years (range, 65-94 years). Minimum
      followup was 12 months (mean, 23 months; range, 12-36 months). RESULTS: Mean
      postoperative American Shoulder and Elbow Surgeons score was 78 (range, 36-98),
      mean active forward flexion was 139 degrees  (range, 90 degrees -180 degrees ),
      and mean active external rotation was 27 degrees  (range, 0 degrees -45 degrees
      ). Mean American Shoulder and Elbow Surgeons pain score was 0.7 (range, 0-5) and
      mean visual analog scale pain score was 1.1 (range, 0-5). Complications were
      identified in three of 30 patients (10%). CONCLUSIONS: At short term, reverse
      total shoulder arthroplasty relieved pain and improved function. The complication
      rate compared favorably with those reported for other treatment alternatives.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 21879404
TI  - Orthopaedic case of the month: Elbow pain in a 9-year-old boy.

PMID- 21879405
TI  - Which factors influence preservation of the osteonecrotic femoral head?
AB  - BACKGROUND: Although surgeons use many procedures to preserve the femoral head in
      patients with hip osteonecrosis, there is no consensus regarding the best
      procedure. QUESTIONS/PURPOSES: We raised the following questions: (1) Is one
      surgical treatment preferred based on published data? (2) What are the rates of
      radiographic progression or conversion to THA after treatment of pre- and
      postcollapse hips? (3) Does lesion size in the femoral head influence
      progression? And (4) does the extent of involvement of the weightbearing surface
      of the femoral head influence outcome? METHODS: We searched MEDLINE and Scopus
      for articles published between 1998 and 2010. We included only articles assessing
      an operative intervention for hip osteonecrosis and having a level of evidence of
      I to IV. We included 54 of the 488 reviewed manuscripts. RESULTS: No procedure
      was superior to others. In pre- and postcollapse hips, 264 of 864 hips (31%) and
      419 of 850 hips (49%), respectively, exhibited radiographic disease progression.
      There were lower failure rates when the lesion involved less than 15% of the
      femoral head or had a necrotic angle of less than 200 degrees  (14%-25%) and when
      the osteonecrotic lesion involved only the medial 1/3 of the weightbearing
      surface (4.6%). CONCLUSIONS: The best treatment of precollapse lesions is
      difficult to determine due to the limitations of the available literature.
      However, the data suggest operative intervention prevents collapse of small
      lesions of the femoral head or when there is a limited amount of the
      weightbearing surface involved. Patients with head collapse have a high
      progression rate after a femoral head-saving procedure.

PMID- 21879406
TI  - Accumulation of fatty marrow in the osteonecrotic hip mimicking joint infection.
AB  - BACKGROUND: Factors such as lipids or cholesterol crystals in body fluids can
      cause a spurious elevation of leukocytes (WBC) in an automated cell count. This
      artifact can occur in automated WBC counts of hip fluid from femoral head
      osteonecrosis (ON), and an erroneous diagnosis of septic arthritis can be made.
      QUESTION/PURPOSES: We describe the frequency of this artifactual leukocytosis in
      femoral head ON and how to differentiate it from septic arthritis. METHODS: From
      September 1997 to June 2004, 414 patients (486 hips) with femoral head ON were
      scheduled to undergo THAs. Although we had no preoperative suspicion of
      infection, we intraoperatively suspected concomitant pyogenic arthritis in eight
      patients (eight hips) because pus-like fluid gushed from the joint during the
      operation. To confirm the presence or absence of infection we intraoperatively
      evaluated the joint fluid with automated blood cell count and microscopy. The
      automated WBC count was elevated in all eight patients. In seven of the eight
      patients, WBCs were not identified under microscopic observation and the
      leukocytosis of automated cell counting was considered to be erroneous. These
      seven patients underwent THAs. The minimum followup was 3 years (average, 45
      months; range, 36-60 months). RESULTS: These seven patients were considered to
      have a spurious elevation of WBC (range, 4500-18,400/mm(3); mean, 8970/mm(3)) in
      an automated cell count. The prevalence of the spurious leukocytosis was 1.4%
      (7/414) in osteonecrotic hips. In all seven patients, we observed numerous fat
      cells and globules instead of WBCs under microscopic observation. No bacteria
      were seen in the smear and culture of the joint fluid. The seven patients
      underwent THAs, and no patient had a subsequent deep wound infection as of the
      last followup. CONCLUSIONS: Fatty joint effusion in an osteonecrotic hip may
      appear like pus and erroneously can be interpreted as leukocytes in an automated
      cell count. In this situation, a microscopic evaluation of joint fluid smear
      should be performed to determine the presence of infection and the treatment
      method. LEVEL OF EVIDENCE: Level III, prognostic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 21879407
TI  - Endoprosthetic treatment is more durable for pathologic proximal femur fractures.
AB  - BACKGROUND: Pathologic proximal femur fractures result in substantial morbidity
      for patients with skeletal metastases. Surgical treatment is widely regarded as
      effective; however, failure rates associated with the most commonly used
      operative treatments are not well defined. QUESTIONS/PURPOSES: We therefore
      compared surgical treatment failure rates among intramedullary nailing,
      endoprosthetic reconstruction, and open reduction-internal fixation when applied
      to impending or displaced pathologic proximal femur fractures. PATIENTS AND
      METHODS: We retrospectively compared the clinical course of 298 patients who
      underwent intramedullary nailing (n = 82), endoprosthetic reconstruction (n =
      197), or open reduction-internal fixation (n = 19) from 1993 to 2008. Primary
      outcome was treatment failure, which was defined as reoperation for any reason.
      Treatment groups were compared for differences in demographic and clinical
      parameters. RESULTS: The number of treatment failures in the endoprosthetic
      reconstruction group (3.1%) was significantly lower than in the intramedullary
      nailing (6.1%) and open reduction-internal fixation (42.1%) groups. The number of
      revisions requiring implant exchange also was significantly lower for
      endoprosthetic reconstruction (0.5%), compared with intramedullary nailing (6.1%)
      and open reduction-internal fixation (42.1%). CONCLUSIONS: Endoprosthetic
      reconstruction is associated with fewer treatment failures and greater implant
      durability. Prospective studies are needed to determine the impact of operative
      strategy on function and quality of life. LEVEL OF EVIDENCE: Level III,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 21879408
TI  - Alumina-on-alumina THA in patients with juvenile idiopathic arthritis: a 5-year
      followup study.
AB  - BACKGROUND: THA is a concern in juvenile idiopathic arthritis (JIA) owing to
      patients' youth, poor bone stock, and small physical size. QUESTIONS/PURPOSES: We
      asked whether (1) uncemented alumina-on-alumina THAs have good clinical and
      radiographic results at midterm followup in young patients with inflammatory
      arthritis and end-stage hip disease secondary to JIA, and (2) the anatomic center
      of rotation of the hip could be reconstructed in patients with acetabular
      protrusion. We also assessed the rate of surgical complications. PATIENTS AND
      METHODS: We retrospectively reviewed 31 alumina-on-alumina THAs in 21 patients
      with a mean age of 30.9 years (range, 14-48 years). Minimum followup until the
      time of revision of any component or the latest evaluation was 16 months. For
      nonrevised cases, the minimum followup was 60 months (range, 60-108 months).
      Acetabular protrusion was mild in 17 hips (Group 1) and moderate-severe in 14
      (Group 2). Bone autograft was used to reconstruct the acetabulum in Group 2.
      Acetabular reconstruction was evaluated according to Ranawat et al. RESULTS: One
      cup was revised owing to aseptic loosening at 16 months; the remaining hips
      showed good clinical and radiographic results. The mean postoperative horizontal
      distance and the distance between the center of the head of the prosthesis and
      the true center of the femoral head improved in Group 2. There were no
      complications related to alumina. CONCLUSIONS: Although THA is a technically
      demanding procedure in patients with JIA, uncemented alumina-on-alumina THA
      provides pain relief and improves quality of life. In patients with acetabular
      protrusion, bone grafts enable anatomic cup positioning. Continued followup will
      be required to determine whether the alumina-on-alumina bearings in patients with
      JIA result in less osteolysis and loosening. LEVEL OF EVIDENCE: Level IV,
      therapeutic study. See Guidelines for Authors for a complete description of
      levels of evidence.

PMID- 21879409
TI  - Endoprostheses last longer than intramedullary devices in proximal femur
      metastases.
AB  - BACKGROUND: The proximal femur is the most common site of surgery for bone
      metastases, and stabilization may be achieved through intramedullary fixation
      (IMN) or endoprosthetic reconstruction (EPR). Intramedullary devices are less
      expensive, less invasive, and may yield improved function over endoprostheses.
      However, it is unclear which, if either, has any advantages. QUESTIONS/PURPOSES:
      We determined whether function, complications, and survivorship differed between
      the two approaches. METHODS: We retrospectively reviewed 158 patients with 159
      proximal femur metastatic lesions treated with surgical stabilization. Forty-six
      were stabilized with IMN and 113 were treated with EPR. The minimum followup was
      0.25 months (mean, 16 months; median, 17 months; range, 0.25-86 months). RESULTS:
      The mean Musculoskeletal Tumor Society score was 24 of 30 (80%) after IMN and 21
      of 30 (70%) after EPR. There were 12 complications (26%) in the IMN group,
      including 10 nonunions, six of which went on to mechanical failure. There were
      complications in 20 of 113 (18%) of the EPR group, which consisted of 10
      dislocations (9%) and 10 infections (9%). There were no mechanical failures with
      EPR. Both implants remained functional for the limited lifespan of these patients
      in each group at all time intervals. EPRs were associated with increased implant
      longevity compared with IMNs (100% versus 85% 5-year survival, respectively) and
      a decreased rate of mechanical failure (0% versus 11%, respectively) when
      compared with the intramedullary devices. CONCLUSIONS: Patients with metastatic
      disease to the proximal femur may live for long periods of time, and these
      patients may undergo stabilization with either IMN or EPR with comparable
      functional scores and the implant survivorship exceeding patient survivorship at
      all time intervals. Endoprostheses demonstrate a lower mechanical failure rate
      and a higher rate of implant survivorship without mechanical failure than IMN
      devices. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for
      Authors for a complete description of levels of evidence.

PMID- 21879410
TI  - Are African American patients more likely to receive a total knee arthroplasty in
      a low-quality hospital?
AB  - BACKGROUND: Total joint arthroplasty is widely performed in patients of all races
      with severe osteoarthritis. Prior studies have reported that African American
      patients tend to receive total joint arthroplasties in low-volume hospitals
      compared with Caucasian patients, suggesting potential racial disparity in the
      quality of arthroplasty care. QUESTIONS/PURPOSES: We asked whether (1) a hospital
      outcome measure of risk-adjusted mortality or complication rate within 90 days of
      primary TKA can be directly used to profile hospital quality of care, and (2)
      African Americans were more likely to receive TKAs at low-quality hospitals (or
      hospitals with higher risk-adjusted outcome rate) compared with Caucasian
      patients. PATIENTS AND METHODS: We developed a risk-adjusted, 90-day
      postoperative outcome measure to identify high-, intermediate-, and low-quality
      hospitals based on patient records in the Medicare Provider Analysis and Review
      files between July 1, 2002, and June 30, 2005 (the first cohort). We then
      analyzed a second cohort of African American and Caucasian patients receiving
      Medicare who underwent primary TKAs between July and December 2005 to determine
      the independent impact of race on admissions to high-, intermediate-, and low
      quality hospitals. RESULTS: The risk-adjusted postoperative
      mortality/complication rate varied substantially across hospitals; hospitals can
      be meaningfully categorized into quality groups. In the second cohort of
      admissions, 8% of African American patients (n = 4894) versus 9.2% of Caucasian
      patients (n = 86,705) were treated in high-quality hospitals whereas 14.7% of
      African American patients versus 12.7% of Caucasians patients were treated in low
      quality hospitals. After controlling for patient demographic, socioeconomic,
      geographic, and diagnostic characteristics, the odds ratio for admission to low
      quality hospitals was 1.28 for African American patients compared with Caucasian
      patients (95% CI, 1.18-1.41). CONCLUSIONS: Among elderly Medicare beneficiaries
      undergoing TKA, African American patients were more likely than Caucasian
      patients to be admitted to hospitals with higher risk-adjusted postoperative
      rates of complications or mortality. Future work is needed to address the
      residential, social, and referring factors that underlie this disparity and
      implications for outcomes of care.

PMID- 21879412
TI  - Does international normalized ratio level predict pulmonary embolism?
AB  - BACKGROUND: Preventing pulmonary embolism is a priority after major
      musculoskeletal surgery. The literature contains discrepant data regarding the
      influence of anticoagulation on the incidence of pulmonary embolism after joint
      arthroplasty. The American College of Chest Physicians guidelines recommend
      administration of oral anticoagulants (warfarin), aiming for an international
      normalized ratio (INR) level between 2 and 3. However, recent studies show
      aggressive anticoagulation (INR > 2) can lead to hematoma formation and increased
      risk of subsequent infection. QUESTIONS/PURPOSES: We asked whether an INR greater
      than 2 protects against pulmonary embolism. PATIENTS AND METHODS: We identified
      9112 patients with 10,122 admissions for joint arthroplasty between 2004 and
      2008. All patients received warfarin for prophylaxis, aiming for an INR level of
      2 or lower. We assessed 609 of 10,122 admissions (6%) for pulmonary embolism
      using CT, ventilation/perfusion scan, or pulmonary angiography, and 163 of 10,122
      admissions (1.6%) had a proven pulmonary embolism. RESULTS: Fifteen of 163
      admissions (9%) had an INR greater than 2 before or on the day of workup compared
      to 35 of 446 admissions (8%) who were negative. We observed no difference between
      the INR values in patients with or without pulmonary embolism. CONCLUSIONS: We
      found no clinically relevant difference in the INR values of patients who did or
      did not develop pulmonary embolism. The risk of bleeding should be weighed
      against the risk of pulmonary embolism when determining an appropriate target INR
      for each patient, as an INR less than 2 may reduce the risk of bleeding while
      still protecting against pulmonary embolism. LEVEL OF EVIDENCE: Level III,
      therapeutic study. See Instructions to Authors for a complete description of
      levels of evidence.

PMID- 21879413
TI  - Classification of three-dimensional thoracic deformities in adolescent idiopathic
      scoliosis from a multivariate analysis.
AB  - PURPOSE: Understanding how to classify and quantify three-dimensional (3D) spinal
      deformities remains an open question in adolescent idiopathic scoliosis. The
      objective of this study was to perform a 3D manifold characterization of
      scoliotic spines demonstrating thoracic deformations using a novel geometric and
      intuitive statistical tool to determine patterns in pathological cases. METHODS:
      Personalized 3D reconstructions of thoracic (T)/lumbar (L) spines from a cohort
      of 170 Lenke Type-1 patients were analyzed with a non-linear manifold embedding
      algorithm in order to reduce the high-dimensionality of the data, using
      statistical properties of neighbouring spine models. We extracted sub-groups of
      the data from the underlying manifold structure using an unsupervised clustering
      algorithm to understand the inherent distribution and determine classes of
      pathologies which appear from the low-dimensional space. RESULTS: For Lenke Type
      1 patients, four clusters were detected from the low-dimensional manifold of 3D
      models: (1) normal kyphosis (T) with hyper-lordosis (L) and high Cobb angles (37
      cases), (2) low kyphosis (T) and normal lordosis (L), with high rotation of plane
      of maximum curvature (55 cases), (3) hypo-kyphotic (T) and hyper-lordosis (L) (21
      cases) and (4) hyper-kyphotic (T) with strong vertebral rotation (57 cases).
      Results show the manifold representation can potentially be useful for
      classification of 3D spinal pathologies such as idiopathic scoliosis and serve as
      a tool for understanding the progression of deformities in longitudinal studies.
      CONCLUSIONS: Quantitative evaluation illustrates that the complex space of spine
      variability can be modeled by a low-dimensional manifold and shows the existence
      of an additional hyper-kyphotic subgroup from the cohort of 3D spine
      reconstructions of Lenke Type-1 patients when compared with previous findings on
      the 3D classification of spinal deformities.

PMID- 21879417
TI  - CME instructions: the nuclear cardiology report: problems, predictors, and
      improvement. A report from the ICANL database.

PMID- 21879414
TI  - Anterior surgery in selective patients with massive ossification of posterior
      longitudinal ligament of cervical spine: technical note.
AB  - STUDY DESIGN: The study includes case series, technical note and review of
      literature. OBJECTIVE: The objective of this study was to assess the validity of
      the radiographic indicator and the result of anterior operation for massive
      ossification of posterior longitudinal ligament (MOPLL, ossification of posterior
      longitudinal ligament with an occupying ratio exceeding 50%). Anterior
      decompression yielded a better outcome than posterior approach in patients with
      MOPLL of cervical spine. But anterior surgery has the problem of technically
      demanding and was associated with a high incidence of surgery-related
      complications. Many ways for reducing the risk of anterior surgery have been
      reported, including floating method, employing microscopes or burrs, and laser
      assisted corpectomy. MATERIALS AND METHODS: A case series of selective patients
      with MOPLL of cervical spine undergoing anterior surgery is reported. All
      patients were strictly selected based on CT images with the appearance of open
      base. 29 cases with more than 12 months follow-up (average, 31.0 +/- 10.0 m) were
      reviewed. Average age at operation was 59.3 +/- 8.2 years (43-73 years). Anterior
      decompression was done only for one or two vertebrae. RESULTS: One corpectomy was
      done in 13 cases, two corpectomies in 3 cases, and one corpectomy and one
      discectomy in 13 cases. Three levels were fused in 16 cases and two levels in 13
      cases. No permanent neurological deterioration was observed. Neurological
      improvement was observed in every patients with an average improvement rate of 64
      +/- 23%. Mesh migration was observed in one case. A fusion rate of 100% was
      achieved. CONCLUSION: Anterior surgery using our technique may be a relatively
      simple and safe procedure in selective patients with massive ossification of
      posterior longitudinal ligament of cervical spine.

PMID- 21879418
TI  - The costs of switching attentional sets.
AB  - People prioritize those aspects of the visual environment that match their
      attentional set. In the present study, we investigated whether switching from one
      attentional set to another is associated with a cost. We asked observers to
      sequentially saccade toward two color-defined targets, one on the left side of
      the display, the other on the right, each among a set of heterogeneously colored
      distractors. The targets were of the same color (no attentional set switch
      required) or of different colors (switch of attentional sets necessary), with
      each color consistently tied to a side, to allow observers to maximally prepare
      for the switch. We found that saccades were less accurate and slower in the
      switch condition than in the no-switch condition. Furthermore, whenever one of
      the distractors had the color associated with the other attentional set, a
      substantial proportion of saccades did not end on the target, but on this
      distractor. A time course analysis revealed that this distractor preference
      turned into a target preference after about 250-300 ms, suggesting that this is
      the time required to switch attentional sets.

PMID- 21879419
TI  - Fechner, information, and shape perception.
AB  - How do retinal images lead to perceived environmental objects? Vision involves a
      series of spatial and material transformations--from environmental objects to
      retinal images, to neurophysiological patterns, and finally to perceptual
      experience and action. A rationale for understanding functional relations among
      these physically different systems occurred to Gustav Fechner: Differences in
      sensation correspond to differences in physical stimulation. The concept of
      information is similar: Relationships in one system may correspond to, and thus
      represent, those in another. Criteria for identifying and evaluating information
      include (a) resolution, or the precision of correspondence; (b) uncertainty about
      which input (output) produced a given output (input); and (c) invariance, or the
      preservation of correspondence under transformations of input and output. We
      apply this framework to psychophysical evidence to identify visual information
      for perceiving surfaces. The elementary spatial structure shared by objects and
      images is the second-order differential structure of local surface shape.
      Experiments have shown that human vision is directly sensitive to this higher
      order spatial information from interimage disparities (stereopsis and motion
      parallax), boundary contours, texture, shading, and combined variables.
      Psychophysical evidence contradicts other common ideas about retinal information
      for spatial vision and object perception.

PMID- 21879420
TI  - Improved lymph node harvest from resected colon cancer specimens did not cause
      upstaging from TNM stage II to III.
AB  - BACKGROUND: The number of lymph nodes retrieved and examined from a resected
      colon cancer specimen may be crucial for correct staging. We examined if efforts
      to increase the lymph node harvest to more than 12 lymph nodes per specimen would
      upstage some patients from TNM stage II to III. METHODS: Three hospitals compared
      results from 2000 with those of 2007 in 421 resected patients with stage II and
      III colon cancer. Hospital A endeavored to improve the surgical procedure while
      the pathologists enhanced the quality of lymph node sampling. Hospital B did not
      make any marked changes, while hospital C introduced the GEWF lymph node solvent
      (glacial acetic acid, ethanol, distilled water, and formaldehyde) in their
      pathology method. RESULTS: In 2000, 12 or more lymph nodes were harvested in
      39.6, 45.0, and 21.1% of the specimens from the three hospitals, while the
      figures for 2007 were 85.7, 42.0, and 90.3%, respectively. The significant
      increase in lymph node harvest in two of the hospitals in 2007 compared to 2000
      (p < 0.001) did not affect the share of patients with stage III in 2007 (38.7%)
      compared to 2000 (44.1%) (p = 0.260). The number of positive lymph nodes and the
      lymph node ratio (LNR) decreased from 2000 to 2007. A lymph node yield of 12 or
      more was not associated with an increased probability of positive lymph nodes in
      a multivariable logistic regression analysis. CONCLUSION: More radical surgery
      and dedicated pathologists and the use of the GEWF solvent significantly
      increased the lymph node yield but did not upstage patients from TNM stage II to
      III.

PMID- 21879421
TI  - Factors associated with recurrence within 2 years after curative surgery for
      gastric adenocarcinoma.
AB  - BACKGROUND: Despite curative surgery for gastric cancer, many patients die of
      recurrent cancer. Few studies have investigated the time to recurrence after
      curative resection for gastric cancer. METHODS: Data were collected prospectively
      between December 1987 and December 2006. A total of 1,549 patients underwent
      curative resection of adenocarcinoma of the stomach at Taipei Veterans General
      Hospital. Among them, 419 patients had recurrence; they were divided into early
      recurrence (<2 years) and late recurrence (>=2 years). The clinicopathological
      characteristics, survival time after recurrence, and recurrence patterns were
      compared between the two groups. RESULTS: Multivariate analysis showed that stage
      III gastric cancer patients with early recurrence had larger tumors and more
      lymph node metastasis than patients with late recurrence, while no difference
      between early and late recurrence was observed in stage I and II patients. Early
      recurrence was associated with more distant metastasis than was late recurrence.
      Patients with advanced TNM stage tended to die within 2 years after recurrence.
      CONCLUSIONS: Gastric cancer patients with larger tumors and more lymph node
      metastasis tended to have early recurrence, especially stage III patients.
      Advanced TNM stage was associated with early cancer death after recurrence.

PMID- 21879422
TI  - Staging of peripheral-type intrahepatic cholangiocarcinoma: appraisal of the new
      TNM classification and its modifications.
AB  - BACKGROUND: In the seventh edition, the TNM classification for intrahepatic
      cholangiocarcinoma (IHC) is separated from that for hepatocellular carcinoma.
      Because it is the first independent classification for IHC, the validity of the
      new classification needs to be evaluated. METHODS: The medical records of 93
      patients with peripheral-type IHC who underwent treatment (61 resected and 32
      unresectable tumors) were retrospectively reviewed focusing on the new TNM
      classification for IHC. RESULTS: The 5-year survival rate and the median survival
      time for the 61 patients with resected tumors were 33.9% and 2.05 years,
      respectively. The survival of the patients with periductal invasion was similar
      to that of the patients without. The survival of the patients with metastasis to
      the gastrohepatic lymph nodes (G-LN) was dismal without any 2-year survivors and
      similar to that of the patients with unresectable tumors (P = 0.247). On
      multivariate analysis, histologic differentiation (P = 0.034), multiple tumors (P
      = 0.014), lymph node metastasis (P < 0.001), and distant metastasis other than
      lymph node metastasis (P = 0.007) were identified as independent prognostic
      factors. According to the above results, we modified the new TNM classification
      as follows: IHC with multiple tumors was classified as pT4 disease; periductal
      invasion was excluded from determinant of the T-categories; and metastasis to G
      LN was treated as distant metastasis. The survival curves based on our
      modifications were better stratified than those based on the new TNM
      classification. CONCLUSIONS: The TNM classification for IHC included some
      clinical inconsistencies; therefore, we proposed some modifications of the new
      TNM classification for IHC and demonstrated that these modifications offer better
      stratification of the survival data. Further revisions are necessary for its
      improvement.

PMID- 21879423
TI  - The surgical treatment of Graves' disease in children and adolescents.
AB  - BACKGROUND: Surgery as definitive treatment of pediatric Graves' disease is
      recommended for children and adolescents experiencing adverse effects of
      thionamides or disease relapse after at least 2 years of medical treatment. In
      addition, it is indicated in patients with a large goiter or with suspicious
      nodules. Total or near-total thyroidectomy should be performed, since subtotal
      thyroidectomy is associated with a high risk of relapse in this group. Patients
      should be referred to surgeons experienced in thyroid surgery because studies
      show that children and adolescents have a higher complication rate than adults.
      METHODS: This is a retrospective matched case-control study. To analyze
      postoperative morbidity of children and adolescents (mean age = 15 +/- 3 years)
      with Graves' disease who underwent total thyroidectomy between 2000 and 2010 in
      our department, a statistically identical group of adults (mean age = 46 +/- 3)
      who also underwent total thyroidectomy for Graves' disease was matched as a
      control. End points were surgical complications like postoperative bleeding,
      transient and permanent recurrent laryngeal nerve palsy, and transient and
      permanent hypoparathyroidism. RESULTS: There was no significant difference in the
      mean operation time (137 +/- 33 min), the rate of intraoperative parathyroid
      gland autotransplantation (9.5%), postoperative bleeding (4.8%), transient and
      permanent recurrent laryngeal nerve palsy (4.8 and 0%), and transient and
      permanent hypocalcemia (28.6 and 0%). CONCLUSION: Total thyroidectomy in children
      and adolescents with Graves' disease performed in a department that specializes
      in endocrine surgery is a safe procedure with no higher complication rates than
      total thyroidectomy in adults with Graves' disease.

PMID- 21879424
TI  - Incidence and prevention of postoperative venous thromboembolism: are they
      meaningful quality indicators in Japanese health care settings?
AB  - BACKGROUND: Venous thromboembolism (VTE) epidemiology varies widely across
      surgical procedures. At present, there are few epidemiologic reports regarding
      VTE in Japan. Japanese VTE prophylaxis guidelines recommend a risk-based approach
      based on previous epidemiologic statistics. VTE includes deep vein thrombosis
      (DVT) and pulmonary embolism (PE). PE prevention is the main goal, although the
      relation between PE and DVT is still controversial. METHODS: We collected
      administrative data for 1,016,496 surgical patients from 260 hospitals. We
      analyzed DVT and PE incidence and selected two subgroups for further analysis:
      gastroenterologic surgery and specific orthopedic surgery (high-frequency group).
      RESULTS: Overall DVT incidence was 1947 (0.19%); and the PE incidence was 538
      (0.05%). DVT case fatality rate was 3.44% (67/1947); that for PE was 22.86%
      (123/538). Both overall and subgroup incidences were comparable to those in
      previous reports. Subgroup analyses in the high-frequency group did not show a
      relation between DVT and PE. VTE prophylaxis did not show a relation between DVT
      and PE despite 82.0% [corrected] adherence. CONCLUSIONS: Our results are
      consistent with established data regarding DVT and PE incidence. Administrative
      data available in Japan provides a powerful epidemiologic tool to characterize
      rare diseases such as DVT and PE. DVT is not a suitable quality indicator in
      Japan. However, PE is too rare to be considered a rate-based outcome indicator,
      and VTE prophylaxis is [corrected] widely applied to be used as a process
      indicator. VTE measurement is not a useful quality indicator in Japan to compare
      hospitals but provides a longitudinal self-survey.

PMID- 21879425
TI  - Global financial crisis and surgical practice: the Greek paradigm.
AB  - Apart from the significant implications of recent financial crisis in overall
      health indices and mortality rates, the direct effect of health resources
      redistribution in everyday clinical practice is barely recognized. In the case of
      Greece, health sector reform and health spending cuts have already had a major
      impact on costly interventions, particularly in surgical practice. An increase in
      utilization of public health resources, lack of basic and advanced surgical
      supplies, salary deductions, and emerging issues in patient management have
      contributed to serious dysfunction of a public health system unable to sustain
      current needs. In this context, significant implications arise for the surgeons
      and patients as proper perioperative management is directly affected by reduced
      public health funding. The surgical community has expressed concerns about the
      quality of surgical care and the future of surgical progress in the era of the
      European Union. Greek surgeons are expected to support reform while maintaining a
      high level of surgical care to the public. The challenge of cost control in
      surgical practice provides, nevertheless, an excellent opportunity to reconsider
      health economics while innovation through a more traditional approach to the
      surgical patient should not be precluded. A Greek case study on the extent of the
      current situation is presented with reference to health policy reform, serving as
      an alarming paradigm for the global community under the pressure of a profound
      financial recession.

PMID- 21879426
TI  - Lithium-associated hyperparathyroidism: surgical strategies in the era of
      minimally invasive parathyroidectomy.
AB  - BACKGROUND: Lithium remains an effective treatment of bipolar affective disorder.
      The long-term use of lithium is associated with an alteration in parathyroid
      function that may culminate in hyperparathyroidism. The long-term effects of
      lithium use are variable due to its complex effects on calcium homeostasis and
      bone metabolism, and as a consequence the indications for surgery remain poorly
      defined. The optimal surgical strategy for lithium-associated hyperparathyroidism
      in the era of minimally invasive surgery is also the subject of debate. The aim
      of the present study was to evaluate the variable findings of lithium-associated
      parathyroid disease. METHODS: A retrospective review was performed of patients
      undergoing parathyroid surgery presenting with lithium-associated
      hyperparathyroidism from July 1999 until July 2009 at the university hospital La
      Timone, Marseille, and from October 2005 to July 2009 at Hammersmith Hospital,
      Imperial College, London. Fifteen patients underwent surgery for lithium
      associated hyperparathyroidism. Clinical data including patient demographics,
      duration of lithium use, clinical manifestations of hyperparathyroidism,
      indications for surgery, and biochemical parameters preoperatively and
      postoperatively were reviewed. Preoperative imaging, the surgical procedure
      performed, operative findings, and histopathology were also analyzed. RESULTS:
      All 15 patients had preoperative imaging: sestamibi scanning showed that 10
      patients had localized single-gland disease, 1 had multiple hot spots, and 4 had
      a negative scan. Ultrasonography demonstrated a single abnormal gland in 8
      patients and multiple enlarged glands in 1 patient; the test was negative in 6.
      As a consequence of concordant preoperative imaging a minimally invasive approach
      (endoscopic or a focused lateral approach) was adopted in 3 patients. Focused
      surgery demonstrated an enlarged hyperplastic gland in 3 cases and resulted in
      normocalcemia in the immediate postoperative period. However, one patient has a
      serum calcium at the upper limit of normal and elevated parathyroid hormone (PTH)
      levels, suggestive of possible recurrence of disease at 15 months follow-up. One
      patient has permanent hypoparathyroidism. In those patients who had open
      procedures, final histology showed hyperplastic multiglandular disease in 10
      patients (83.3%) of patients and single-gland disease in 2 patients (16.7%). None
      of these patients show evidence of recurrence at follow-up. CONCLUSIONS: Lithium
      hyperparathyroidism is predominantly a multiglandular disease characterized by
      asymmetrical hyperplasia that is frequently associated with misleading or
      discordant localization studies. Bilateral neck exploration is therefore
      recommended in order to minimize the risk of disease recurrence.

PMID- 21879427
TI  - Crossing the boundaries of 'colonial psychiatry'. Reflections on the development
      of psychiatry in British India, C. 1870-1940.
AB  - This article explores the development of psychiatric institutions within the
      context of British colonial rule in India, in particular during the late
      nineteenth and early twentieth centuries. Existing scholarship on 'colonial
      medicine' has tended to focus on colonial power and hegemony and the British
      endeavour to 'colonize the Indian body' during the nineteenth century. It is
      suggested here that reference to 'colonial' medicine and psychiatry tends to
      reify the ideology of colonialism and neglect other important dimensions such as
      the role of international scientific networks and the mental hospital as the
      locus of care and medicalization. From the later period of British colonial
      engagement in south Asia, people's right and entitlement to medical care and the
      colonial state's obligation to provide institutional treatment facilities
      received increased attention. As the early twentieth-century case of an Indian
      hospital superintendent shows, practitioners' professional ambitions went beyond
      the confines of 'colonial psychiatry'. He practiced in his institution science
      based psychiatry, drawing on models and treatment paradigms that were then
      prevalent in a variety of countries around the globe.

PMID- 21879428
TI  - Sexual satisfaction, relationship satisfaction, and health are associated with
      greater frequency of penile-vaginal intercourse.

PMID- 21879429
TI  - Judgments of sexual orientation and masculinity-femininity based on thin slices
      of behavior: a cross-cultural comparison.
AB  - Studies of North Americans suggest that laypeople can judge the sexual
      orientation of others with greater than chance accuracy based on brief
      observations of their behavior (i.e., "gaydar" exists). One factor that appears
      to contribute to these judgments is targets' degree of masculinity-femininity.
      However, behaviors related to sexual orientation and to masculinity-femininity
      might vary across cultures. Thus, cross-cultural work is needed to test whether
      judgments of sexual orientation are more accurate when targets and raters are
      from the same culture. American and Czech male targets, 38 homosexual and 41
      heterosexual, were videotaped and brief segments of the videotapes were presented
      to American and Czech raters. Overall, raters' judgments of targets' sexual
      orientation were related to targets' self-reported sexual orientation. However,
      the relationship was stronger when targets were judged by raters from their own
      country. In general, results suggest that there are both cross-cultural
      similarities and differences in gaydar and in cues related to sexual orientation.

PMID- 21879430
TI  - Body odor quality predicts behavioral attractiveness in humans.
AB  - Growing effort is being made to understand how different attractive physical
      traits co-vary within individuals, partly because this might indicate an
      underlying index of genetic quality. In humans, attention has focused on
      potential markers of quality such as facial attractiveness, axillary odor
      quality, the second-to-fourth digit (2D:4D) ratio and body mass index (BMI). Here
      we extend this approach to include visually-assessed kinesic cues (nonverbal
      behavior linked to movement) which are statistically independent of structural
      physical traits. The utility of such kinesic cues in mate assessment is
      controversial, particularly during everyday conversational contexts, as they
      could be unreliable and susceptible to deception. However, we show here that the
      attractiveness of nonverbal behavior, in 20 male participants, is predicted by
      perceived quality of their axillary body odor. This finding indicates covariation
      between two desirable traits in different sensory modalities. Depending on two
      different rating contexts (either a simple attractiveness rating or a rating for
      long-term partners by 10 female raters not using hormonal contraception), we also
      found significant relationships between perceived attractiveness of nonverbal
      behavior and BMI, and between axillary odor ratings and 2D:4D ratio. Axillary
      odor pleasantness was the single attribute that consistently predicted
      attractiveness of nonverbal behavior. Our results demonstrate that nonverbal
      kinesic cues could reliably reveal mate quality, at least in males, and could
      corroborate and contribute to mate assessment based on other physical traits.

PMID- 21879431
TI  - A case of perforative peritonitis caused by a piece of bamboo in a patient on
      peritoneal dialysis.
AB  - We report a case of peritonitis resulting from colon perforation caused by
      ingestion of a rare foreign body in a patient on peritoneal dialysis (PD). A 72
      year-old woman on PD was hospitalized with abdominal pain and cloudy PD fluid
      (PDF). Although conventional antibiotic therapy was started because of a
      diagnosis of infectious peritonitis, low-grade fever, abdominal pain and a high
      number of white blood cells in PDF persisted. On day 3, anaerobic bacteria were
      recognized on bacterial culture of PDF, suggesting a gastrointestinal etiology.
      During exploratory laparotomy, sigmoidal perforation by a piece of bamboo,
      probably resulting from ingestion of contaminated food, was found.

PMID- 21879432
TI  - [Urooncology - our competence!].

PMID- 21879433
TI  - [Interdisciplinary Working Group Bladder Cancer (IABC) in the German Cancer
      Society newly founded].

PMID- 21879434
TI  - [Preoperative evaluation of adult patients prior to elective, non-cardiac
      surgery. Joint recommendations of German Society of Anesthesiology and Intensive
      Care Medicine, German Society of Surgery and German Society of Internal
      Medicine].
AB  - Evaluation of the patient's medical history and a physical examination are the
      cornerstones of risk assessment prior to elective surgery and may help to
      optimize the patient's preoperative medical condition and to guide perioperative
      management. Whether the performance of additional technical tests (e.g. blood
      chemistry, ECG, spirometry, chest-x-ray) can contribute to a reduction of
      perioperative risk is often not very well known or controversial. Similarly,
      there is considerable uncertainty among anesthesiologists, internists and
      surgeons with respect to the perioperative management of the patient's long-term
      medication. Therefore, the German Scientific Societies of Anesthesiology and
      Intensive Care Medicine (DGAI), Internal Medicine (DGIM) and Surgery (DGCH) have
      joined to elaborate and publish recommendations on the preoperative evaluation of
      adult patients prior to elective, non-cardiac and non-lung resection surgery. In
      the first part the general principles of preoperative evaluation are described
      (part A). The current concepts for extended evaluation of patients with known or
      suspected major cardiovascular disease are presented in part B. Finally, the
      perioperative management of patients' long-term medication is discussed (part C).
      The concepts proposed in these interdisciplinary recommendations endorsed by the
      DGAI, DGIM and DGCH provide a common basis for a structured preoperative risk
      assessment and management. These recommendations aim to ensure that surgical
      patients undergo a rational preoperative assessment and at the same time to avoid
      unnecessary, costly and potentially dangerous testing. The joint recommendations
      reflect the current state-of-the-art knowledge as well as expert opinions because
      scientific-based evidence is not always available. These recommendations will be
      subject to regular re-evaluation and updating when new validated evidence becomes
      available.

PMID- 21879439
TI  - [Common infections in internal medicine].

PMID- 21879443
TI  - K-acetylation and its enzymes: overview and new developments.
AB  - Lysine (K) acetylation refers to transfer of the acetyl moiety from acetyl-CoA to
      the epsilon-amino group of a lysine residue. This is posttranslational and
      reversible, with its level dynamically maintained by lysine acetyltransferases
      (KATs) and deacetylases (KDACs). Traditionally, eukaryotic KDACs have been
      referred to as HDACs (histone deacetylases). Recent proteomic studies have
      revealed that hundreds of bacterial proteins and thousands of eukaryotic proteins
      contain acetyl-lysine (AcK) residues, indicating that K-acetylomes are comparable
      to phosphoproteomes. The current challenges are to assign enzymes that execute
      specific acetylation events, to determine the impact of these events, and to
      relate this modification to other posttranslational modifications, cell signaling
      networks, and pathophysiology under different cellular and developmental
      contexts. In this chapter, we provide a brief overview about the acetylomes,
      KATs, HDACs, AcK-recognizing protein domains, and acetylation-modulating
      therapeutics, and emphasize the latest developments in related areas. The
      remaining chapters of the book focus on and cover various aspects of HDACs (both
      the Rpd3/Hda1 and sirtuin families), which shall provide novel insights into how
      to utilize these enzymes for developing a new generation of HDAC-related
      therapeutics.

PMID- 21879444
TI  - The biology of HDAC in cancer: the nuclear and epigenetic components.
AB  - Traditionally, cancer has been regarded to originate from genetic alterations
      such as mutations, deletions, rearrangements as well as gene amplifications,
      leading to abnormal expression of tumor suppressor genes and oncogenes. An
      increasing body of evidence indicates that in addition to changes in DNA
      sequence, epigenetic alterations contribute to cancer initiation and progression.
      In contrast to genetic mutations, epigenetic changes are reversible and therefore
      an attractive target for cancer therapy. Many epi-drugs such as histone
      deacetylase (HDAC) inhibitors showed anticancer activity in cell culture and
      animal models of carcinogenesis. Recently, the two HDAC inhibitors
      suberoylanilide hydroxamic acid (SAHA, Vorinostat) and Romidepsin (Depsipeptide,
      FK228) were FDA approved for the treatment of cutaneous T-cell lymphoma (CTCL).
      Although HDAC inhibitors are potent anticancer agents, these compounds act
      against several HDAC family members potentially resulting in numerous side
      effects. This stems from the fact that HDACs play crucial roles in a variety of
      biological processes including cell cycle progression, proliferation,
      differentiation, and development. Consistently, mice deficient in single HDACs
      mostly exhibit severe phenotypes. Therefore, it is necessary to specify the
      cancer-relevant HDACs in a given tumor type in order to design selective
      inhibitors that target only cancer cells without affecting normal cells. In this
      chapter, we summarize the current state of knowledge of individual nuclear HDAC
      family members in development and tumorigenesis, their contribution to the
      hallmarks of cancer, and the involvement of HDAC family members in different
      types of human malignancies.

PMID- 21879445
TI  - Deacetylation of nonhistone proteins by HDACs and the implications in cancer.
AB  - Acetylation and deacetylation of lysine residues controlled by histone
      acetyltransferases (HATs) and histone deacetylases (HDACs), respectively, are
      among the most common posttranslational modifications of proteins. In addition to
      histones, a large number of nonhistone proteins that can undergo reversible
      acetylation have been identified. These nonhistone acetylated/deacetylated
      proteins are involved in a wide range of cellular processes including
      transcription, translation, DNA repair, metabolism, and cell structure. Aberrant
      deacetylation of nonhistone proteins is implicated in many human diseases,
      including cancer. In this chapter, we review and describe the involvement of
      HDACs in cancer-associated cellular processes via deacetylation of nonhistone
      proteins, and the possible implications for carcinogenesis and cancer
      development.

PMID- 21879446
TI  - The biology and therapeutic implications of HDACs in the heart.
AB  - The heart responds to stresses such as chronic hypertension and myocardial
      infarction by undergoing a remodeling process that is associated with myocyte
      hypertrophy, myocyte death, inflammation and fibrosis, often resulting in
      impaired cardiac function and heart failure. Recent studies have revealed key
      roles for histone deacetylases (HDACs) as both positive and negative regulators
      of pathological cardiac remodeling, and small molecule HDAC inhibitors have
      demonstrated efficacy in animal models of heart failure. This chapter reviews the
      functions of individual HDAC isoforms in the heart and highlights issues that
      need to be addressed to enable development of novel HDAC-directed therapies for
      cardiovascular indications.

PMID- 21879447
TI  - HDACs in skeletal muscle remodeling and neuromuscular disease.
AB  - Skeletal muscle is made of heterogeneous myofibers with different contractile and
      metabolic properties. The diverse functionality of myofibers enables skeletal
      muscle to carry out different tasks from maintaining body posture to performing
      active movements. In addition to motility, skeletal muscle, which constitutes 40%
      of body mass, is also a key target of insulin action and performs an essential
      function in glucose metabolism. Adult skeletal muscle is a highly adaptive organ
      system and can undergo specific changes in contractile and metabolic properties
      to meet different functional demands. This plasticity of myofibers reflects a
      highly coordinated change in gene expression program that is controlled by neural
      activity. The capacity for on-demand remodeling confers skeletal muscle the
      remarkable adaptability important for animal survival; its dysregulation,
      however, could contribute to muscle and metabolic diseases. How neural activity
      dictates transcriptional programming to modify muscle functionality and diversity
      is a fundamental issue. Recent studies have identified members of class IIa HDACs
      as important effectors in both physiological and pathological muscle remodeling.
      By way of modifying myofiber properties, pharmacological manipulation of IIa
      HDACs activity could have potential therapeutic utility in the treatment of
      muscle disorders.

PMID- 21879448
TI  - Rationale for HDAC inhibitor therapy in autoimmunity and transplantation.
AB  - While there are currently more than 70 ongoing clinical trials of inhibitors of
      so-called classical HDACs (HDACi) as anticancer therapies, given their potency as
      antiproliferative and angiostatic agents, HDACi also have considerable
      therapeutic potential as anti-inflammatory and immunosuppressive drugs. The
      utility of HDACi as anti-inflammatory agents is dependent upon their proving safe
      and effective in experimental models. Current pan-HDACi compounds are not well
      suited to this role, given the broad distribution of target HDACs and their
      complex and multifaceted mechanisms of action. In contrast, the development of
      isoform-selective HDACi may provide important new tools for therapy in
      autoimmunity and transplantation. This chapter discusses which HDACs are
      worthwhile targets in inflammation and progress toward their therapeutic
      inhibition, including the use of HDAC subclass and isoform-selective HDACi to
      promote the functions of Foxp3+ T regulatory cells.

PMID- 21879451
TI  - Characterization of nuclear sirtuins: molecular mechanisms and physiological
      relevance.
AB  - Sirtuins are protein deacetylases/mono-ADP-ribosyltransferases found in organisms
      ranging from bacteria to humans. This group of enzymes relies on nicotinamide
      adenine dinucleotide (NAD(+)) as a cofactor linking their activity to the
      cellular metabolic status. Originally found in yeast, Sir2 was discovered as a
      silencing factor and has been shown to mediate the effects of calorie restriction
      on lifespan extension. In mammals seven homologs (SIRT1-7) exist which evolved to
      have specific biological outcomes depending on the particular cellular context,
      their interacting proteins, and the genomic loci to where they are actively
      targeted. Sirtuins biological roles are highlighted in the early lethal
      phenotypes observed in the deficient murine models. In this chapter, we summarize
      current concepts on non-metabolic functions for sirtuins, depicting this broad
      family from yeast to mammals.

PMID- 21879452
TI  - Structural biology of human metal-dependent histone deacetylases.
AB  - Class I, II, and IV histone deacetylases (HDACs) are metal-dependent enzymes
      involved in a broad and partly unexplored array of biological mechanisms that
      include epigenetic control of gene expression. The catalytic domain of human
      classes I and IIa enzymes has been solved in complex with a substrate peptide and
      inhibitors, which revealed a conserved architecture, uncovered the catalytic
      mechanism of deacetylation, and outlined a chemical framework for inhibitor
      design. We will review the different structural elements of metal-dependent HDACs
      and their contributions to substrate recognition, catalysis, and inhibitor
      specificity.

PMID- 21879449
TI  - The role of mammalian sirtuins in the regulation of metabolism, aging, and
      longevity.
AB  - Ever since the discovery of sirtuins a decade ago, interest in this family of NAD
      dependent deacetylases has exploded, generating multiple lines of evidence
      implicating sirtuins as evolutionarily conserved regulators of lifespan. In
      mammals, it has been established that sirtuins regulate physiological responses
      to metabolism and stress, two key factors that affect the process of aging.
      Further investigation into the intimate connection among sirtuins, metabolism,
      and aging has implicated the activation of SIRT1 as both preventative and
      therapeutic measures against multiple age-associated disorders including type 2
      diabetes and Alzheimer's disease. SIRT1 activation has clear potential to not
      only prevent age-associated diseases but also to extend healthspan and perhaps
      lifespan. Sirtuin activating compounds and NAD intermediates are two promising
      ways to achieve these elusive goals.

PMID- 21879450
TI  - Mitochondrial sirtuins in the regulation of mitochondrial activity and metabolic
      adaptation.
AB  - In eukaryotes, mitochondria carry out numerous functions that are central to
      cellular and organismal health. How mitochondrial activities are regulated in
      response to differing environmental conditions, such as variations in diet,
      remains an important unsolved question in biology. Here, we review emerging
      evidence suggesting that reversible acetylation of mitochondrial proteins on
      lysine residues represents a key mechanism by which mitochondrial functions are
      adjusted to meet environmental demands. In mammals, three members of the sirtuin
      class of NAD(+)-dependent deacetylases - SIRT3, SIRT4, and SIRT5 - localize to
      mitochondria and regulate targets involved in a diverse array of biochemical
      pathways. The importance of this activity is highlighted by recent studies of
      SIRT3 indicating that this protein suppresses the emergence of diverse age
      related pathologies: hearing loss, cardiac fibrosis, and malignancy. Together,
      these findings argue that mitochondrial protein acetylation represents a central
      means by which mammals regulate mitochondrial functions to maintain cellular and
      organismal homeostasis.

PMID- 21879455
TI  - [Background noise in the procrustean bed: implementation at a new hospital
      reimbursement system in Germany].

PMID- 21879453
TI  - Sirtuin modulators.
AB  - Members of the sirtuin family including the founding protein Sir2 in
      Saccharomyces cerevisiae have been linked to lifespan extension in simple
      organisms. This finding prompted evaluation of the role of Sir2 orthologues in
      many aging-associated conditions including neurodegeneration, type II diabetes
      and cancer. These studies have demonstrated that genetic and pharmacologic
      manipulation of sirtuin activity have beneficial effects in a surprisingly broad
      spectrum of aging-associated conditions suggesting that the Sir2-family of
      enzymes presents an attractive target for the development of pharmacological
      agents. While the initial model favored pharmacological activators of sirtuins as
      calorie restriction mimetics, it now appears that either activation or inhibition
      of sirtuins may be desirable for ameliorating disease depending on the
      pathological condition and the target tissue. In this chapter we review the
      development of pharmacological small molecule activators and inhibitors of the
      sirtuin family of enzymes.

PMID- 21879456
TI  - [Antidepressants for mild depressive disorders].

PMID- 21879457
TI  - Measuring patient safety in neonatology.
AB  - Measurement of patient safety serves to identify opportunities to improve safety
      within a neonatal intensive care unit (NICU), compare the safety of care provided
      by different NICUs, determine changes in response to safety interventions or
      programs, follow safety trends over time, and potentially deny payment for
      specific events. The ideal patient safety measures are rates of events derived
      from surveillance with valid and reliable detection of numerators (errors or
      adverse events) and denominators (the opportunities for errors or adverse events
      to occur). Methods used to identify these numerators and denominators include
      reporting, direct observation, videotaping, chart review, trigger tools, and
      automated methods. However, there are significant methodological and practical
      (feasibility) challenges to the accurate and reliable determination of rates of
      errors and adverse events. These include failure to detect and document such
      events, surveillance bias, lack of consistent definitions, frequent requirement
      for judgment in identifying and classifying challenges (which introduces
      interrater inconsistency), and need for significant additional resources.

PMID- 21879458
TI  - Central line-associated bloodstream infections in neonatal intensive care:
      changing the mental model from inevitability to preventability.
AB  - Previously considered unavoidable complications of hospital care (reflecting an
      "entitlement" mental model), health care-associated infections are now considered
      as medical errors and cause significant preventable morbidity and mortality in
      neonates. Prevention of such infections, particularly central line-associated
      bloodstream infections (CLABSI), should be an important patient safety priority
      for all neonatal intensive care units (NICUs). An important first step is to
      promote a mental model of CLABSIs as preventable complications of care. Other
      general strategies are (1) promoting an organizational culture of safety and
      empowerment of staff; (2) hand hygiene; (3) avoiding overcrowding and
      understaffing; (4) using breast milk for enteral feedings; and (5) involving
      families in infection prevention efforts. Specific strategies to prevent CLABSI
      are (1) insertion practices: insertion of all central vascular catheters under
      strict sterile conditions with the aid of a checklist; (2) maintenance practices:
      ensuring that entries into the lumen of the vascular catheter always occur under
      aseptic conditions, minimizing catheter disconnections, and replacement of
      intravenous infusion sets at recommended intervals; (3) removal of all central
      lines as soon as possible. Participation in national or statewide quality
      improvement collaboratives is an emerging trend in neonatology that can enhance
      CLABSI prevention efforts by NICUs.

PMID- 21879459
TI  - The effect of physician sleep deprivation on patient safety in perinatal-neonatal
      medicine.
AB  - Recent data indicate that as many as 180,000 patients die each year due to harm
      suffered as a result of medical care. Between 40 and 60% of these deaths-and the
      millions of injuries due to medical care-are preventable. In the neonatal
      intensive care unit (NICU), neonates' size and fragility makes them especially
      susceptible to serious medical errors, which occur at a far higher rate in this
      population than elsewhere in hospitals. A growing body of literature demonstrates
      that the work schedules and sleep deprivation of physicians are important
      contributors to this epidemic of error. Nowhere is there a higher risk of adverse
      outcomes due to provider sleep deprivation than in the NICU, where even minor
      lapses of attention or miscalculations can lead to dire patient outcomes. This
      review will discuss what is known about how provider sleep deprivation may impact
      perinatal and neonatal medicine and will discuss ongoing research questions that
      must be addressed to guide future improvement efforts.

PMID- 21879460
TI  - Surgical findings in acquired undescended testis: an explanation for pubertal
      descent or non-descent?
AB  - AIM: Surgical findings were studied to find an explanation for the phenomenon
      that some acquired undescended testes (UDT) descend spontaneously whereas others
      need orchiopexy. METHODS: In patients with acquired UDT spontaneous descent was
      awaited until at least Tanner stage P2G2. Orchiopexy was performed when a stable
      scrotal position had not been achieved by the end of follow-up. RESULTS:
      Orchiopexy was needed in 57 of 132 cases (43%). In cases requiring orchiopexy,
      the difference in testis volume compared to the contralateral healthy testis was
      significantly larger than for spontaneously descended testes. 41 (72%)
      undescended testes were found in the superficial inguinal pouch; 16 (28%) at the
      external annulus. 26 of the 41 testes in the superficial inguinal pouch position
      (63%) could be manipulated preoperatively into a non-stable scrotal position; 15
      could only reach the scrotal entrance prior to surgery. None of the 16 testes
      located at the external annulus could reach a scrotal position. Inguinal
      exploration in most cases revealed a fibrous string or a partially open processus
      vaginalis. CONCLUSION: The mobility of acquired UDT located within the external
      annulus is limited. It is mainly the fibrous string and the partially open
      processus vaginalis that prevent normal elongation of the spermatic cord with
      growth. These testes are unlikely to descend spontaneously. Acquired UDT lying in
      the superficial inguinal pouch can often be pushed down well below the scrotal
      entrance. We speculate that under normal hormonal stimulation at puberty, some of
      these growing testes may overcome the strength of the fibrous string in the
      spermatic cord and descend again spontaneously.

PMID- 21879461
TI  - Immunological effects of acute testicular torsion on the contralateral testis in
      rats.
AB  - AIM: The mechanism by which unilateral testicular torsion leads to injury of the
      contralateral testis is still controversial. The present study aimed to evaluate
      immunohistopathological changes in the contralateral testis of rats after acute
      testicular torsion. METHODS: 40 pubertal rats were randomly divided into 3
      groups. Group 1 (n=10) functioned as controls. Group 2 rats (n=10) underwent a
      sham operation, and Group 3 (n=20) underwent 720 degrees  torsion of the left
      spermatic cord (3 h) followed by detorsion (24 h). RESULTS: Immunofluorescence
      tests were done to investigate contralateral lesions in half of the animals in
      Group 3. Nitro blue tetrazolium (NBT) was injected in both testes to identify the
      presence of oxygen-derived free radicals. 24 h after reperfusion, bilateral
      samples of the testes were obtained for histological analysis. Fisher's exact
      test was used for statistical analysis with p-values <0.05 considered
      significant.Immunofluorescence tests were positive for the contralateral (right)
      testis but with a lower intensity than that of the testis submitted to torsion.
      NBT reaction was intense all over the left testis while a minor reaction was
      visible in the right testis. In Group 3 the left distorted testicle showed
      diffuse edema with cell elimination and extensive necrosis of the seminiferous
      tubules. Histological lesions were moderate to mild in the contralateral testis.
      CONCLUSION: An autoimmune IgG-mediated mechanism deposited on the basement
      membrane of seminiferous tubules seems to be involved in the genesis of
      contralateral testis injury.

PMID- 21879462
TI  - Re-operations for Hirschsprung's disease: long-term complications.
AB  - INTRODUCTION: In some patients with Hirschsprung's disease (HD), the initial
      surgical procedure fails, and the patients suffer from repeated or persistent
      symptoms. These patients complain of severe inflammation, intestinal obstruction,
      fecal or urinary incontinence, abdominal pain or dystrophy. However, little data
      has been published on the long-term follow-up results after re-operations for HD.
      MATERIALS AND METHODS: We followed 8 cases between 2004 and 2006, of complicated
      HD requiring repeated surgery and recorded prior procedures, histological
      results, indications for re-operation, postoperative follow-up as well as long
      term clinical outcomes including stool patterns, nutrition and micturition.
      RESULTS: The follow-up period ranged from 3.0 to 5.5 years (mean: 4.4 years).
      Indications for repeat procedures were as follows: blind rectal pouch after a
      Duhamel operation (n = 2), persistent aganglionosis (n = 4), long-segment
      stenosis (n = 1) after a Rehbein operation, and anal stenosis following TERPT
      (transanal endorectal pull-through) (n = 1). In one patient who had a Duhamel
      Martin operation, extirpation of the rectum and a definitive terminal ileostomy
      was necessary. A Duhamel procedure was performed in five patients with a primary
      Rehbein and 1 patient with a primary Duhamel operation. Complete stool continence
      was achieved in 4 patients. Partial fecal incontinence persisted in one patient
      with associated trisomy 21. 1 patient with total colonic aganglionosis and 1
      patient with a pelvic fistula and a previous subtotal colectomy reported soiling
      1-2 times per week after a repeat operation. 4 patients in our series experienced
      postoperative complications following repeated surgery [perianal ulceration (n =
      2), repeated botulinum toxin injection for sphincter achalasia (n = 1) and
      functionally impaired colonic transit without stenosis (n = 1)]. Micturition was
      normal in 7 patients, 1 patient with associated trisomy 21 was partially
      continent, and 1 patient reported infrequent urge incontinence. CONCLUSIONS: All
      patients improved after further surgical intervention. However, resolution of
      their symptoms was delayed and partial stool incontinence or soiling persisted in
      3 patients. Most complications leading to repeat procedures are preventable,
      especially residual aganglionosis. Therefore, great efforts should be made to
      minimize complications when planning and performing the primary surgery.

PMID- 21879463
TI  - COUP-TFII gene expression is upregulated in embryonic pleuroperitoneal folds in
      the nitrofen-induced congenital diaphragmatic hernia rat model.
AB  - INTRODUCTION: The nitrofen model of congenital diaphragmatic hernia (CDH) creates
      a Bochdalek-type diaphragmatic defect and has been widely used to investigate the
      pathogenesis of CDH. However, the exact pathogenesis of the diaphragmatic defect
      in this model is still poorly understood. Chicken ovalbumin upstream promotor
      transcription factor II (COUP-TFII) is expressed in the embryonic
      pleuroperitoneal folds (PPF) in the early stage of development and in the
      diaphragm in the late days of gestation. COUP-TFII is known to be a strong
      repressor of the retinoid signaling pathway (RSP), which plays an important role
      in diaphragm development. Furthermore, it has been recently shown that COUP-TFII
      is upregulated during early gestation in the nitrofen-induced hypoplastic lung.
      We designed this study to investigate the hypothesis that COUP-TFII gene
      expression is upregulated during early diaphragmatic development in the PPF.
      MATERIAL AND METHODS: Timed pregnant rats were exposed to either olive oil
      (Control) or nitrofen (CDH) on day 9 of gestation (D9). Fetuses were sacrificed
      on D13, D18 or D21. The PPF was dissected from D13 fetuses using laser capture
      microdissection. Diaphragms were dissected from D18 and D21 fetuses under the
      dissection microscope. The relative mRNA expression levels of COUP-TFII were
      determined using real-time PCR. Immunohistochemistry was performed to evaluate
      diaphragmatic protein expression and the distribution of COUP-TFII.Results On
      D13, gene expression levels of COUP-TFII in the PPF were significantly increased
      in the CDH group (82.93 +/- 11.85) compared to Controls (46.22 +/- 8.09; p <
      0.05), whereas there were no differences at later time points. The
      immunoreactivity of diaphragmatic COUP-TFII was markedly increased in the PPF in
      the CDH group compared to controls on D13. No difference in immunoreactivity was
      observed on D18 and D21. CONCLUSION: Upregulation of COUP-II gene expression in
      the PPF may contribute to the diaphragmatic defect in the nitrofen CDH model by
      inhibiting the RSP.

PMID- 21879464
TI  - The global paediatric surgery network: early measures of interest in the website.
AB  - PURPOSE: The Global Paediatric Surgery Network (GPSN) website was launched in May
      2010, with the following goals: to serve as a clearing house for pediatric
      surgery volunteer work performed worldwide, to provide online resources for
      surgeons working in areas of limited medical resources, and to provide practical
      and educational information for surgeons who wish to volunteer. The purpose of
      this study was to assess use of the website over the first year since its launch
      (May 6, 2010-May 5, 2011). METHODS: The GPSN website was examined for number of
      pages, number of listings in Past Work, Present Work, and Help Needed categories,
      as well as number of volunteers available. The online tool Google Analytics was
      used to assess parameters that measure use of the website, such as number of
      visits, number of page views, number of visitors, time on the website, and
      geographic origin of visitors. RESULTS: The GPSN website consists of 30 pages.
      There are 9 listings in Past Work, 23 listings in Present Work, and 13 listings
      in Help Needed categories. 118 people have registered as willing to volunteer,
      and 96 have indicated that they are able to work in times of a natural disaster.
      There were 8437 visits to the website, with 28 916 page views by 5170 visitors
      from 145 countries, with an average number of page views of 3.43 and an average
      time on the website of 4:05 min. The most visited pages were the homepage, the
      meetings page, and the pediatric surgery organizations page. 4 websites of
      pediatric surgery organizations have links to the GPSN website. CONCLUSIONS:
      Based on early website use, we conclude that there is an interest in the GPSN. We
      speculate that participation in the GPSN will continue to grow, but that there is
      a continued need to promote the website in the global pediatric surgery
      community.

PMID- 21879465
TI  - [Patients as customers? The term "customer" in the perception of medical students
      at the end of their university training].
AB  - In the preceding decades a new perspective on the role of patients in the health
      care system has gained ground, considering patients not merely as "suffering
      persons" but additionally as "customers". Physicians, however, tend to disagree
      with this approach because of the economic connotation of the term customer.
      Until now, there is only poor evidence of whether students of medicine - who are
      going to work as physicians in the future - agree or disagree with that approach
      and whether they are ready to accept patients as customers. In the following
      study students of medicine were interviewed on their perspectives towards that
      approach, in particular on their attitudes towards the idea of "the patient as
      customer", the appropriateness of the term consumer in different clinical
      settings and sectors of health care, the implementation of consumer orientation
      in clinical routine, and their favoured model of physician-patient
      relationship.As the study could not build upon data of prior similar studies, a
      quantitative and qualitative cross-sectional study with a descriptive-explorative
      design was conducted. Using a semi-standardised questionnaire, 313 medical
      students (response rate: 95%) were interviewed in Spring 2010. At the time of the
      survey, the students were enrolled at the faculty of medicine at Freiburg
      University, Germany, and were in their last semester which immediately preceded
      their exam.The future physicians do not consider patients primarily as customers.
      More than 80% of the respondents "absolutely" or "largely" supported the idea
      that patients are considerably more than customers. The analysis of the
      qualitative data of the study shows different results. Here, more statements were
      made that patients could equally be seen as customers (449 students supported
      this idea, 298 did not). Statements contradicting the customer approach referred
      mostly to the asymmetry of the physician-patient relationship and the special
      role of the patient. The highest level of acceptance of the customer approach was
      found in classical service settings such as pharmacies, the lowest level in
      emergency medical aid. According to medical students, a consumer orientation has
      been realised in different health service areas in correspondingly different
      degrees: On top of the list are plastic surgery clinics, followed by private
      health insurances and homeopathic clinics. A minority of medical students predict
      the implementation of consumer orientation in the emergency medical aid. Future
      physicians consider their relationship to patients largely as a relationship
      between a healing person and a person seeking help rather than a relationship
      between a service provider and a customer.Considering recent developments in the
      organisation of medical services and health services in general, it becomes
      increasingly important to know what kind of 'service behaviour' patients expect
      from their doctors and other health providers. Obviously, it is not self-evident
      for medical students to perceive their future patients as customers and to act as
      customer-oriented 'service providers'. In view of this, the faculties of medicine
      at universities - which provide professional training to students of medicine -
      should be aware of the challenge to 'socialise' their students so that they can
      keep up with patients' expectations.

PMID- 21879466
TI  - [Smoking in movies and established smoking in adolescence].
AB  - AIM: The aim of this study was to examine whether smoking in movies can predict
      established smoking in adolescence. METHODS: A longitudinal study was conducted
      over a period of 13 months with 4112 German students. Adolescents' exposure to
      smoking in movies was assessed by asking each student to indicate which film he
      or she had seen from a unique list of 50 movies, which was randomly selected for
      each individual survey from a sample of 398 popular contemporary movies. We
      calculated exposure to movie smoking for each respondent by summing the number of
      smoking occurrences for each movie that the respondent reported seeing. RESULTS:
      At follow-up, a total of 272 young people had smoked more than 100 cigarettes
      during their lifetime. While 2.1% of the young people with the lowest exposure to
      movie smoking initiated established smoking, 13.4% of the group with the highest
      exposure to movie smoking initiated established smoking. The adjusted relative
      risk of initiation of established smoking was 2.05 times higher in the group with
      the highest movie smoking exposure compared to the group with the lowest exposure
      (95% confidence interval: 1.25-3.35). CONCLUSION: Our data indicate that smoking
      in movies can be regarded as an independent risk factor for the initiation of
      established smoking in adolescence.

PMID- 21879467
TI  - The characteristics of osteoporotic fractures in the region of Bialystok (BOS-2).
      The application of the WHO algorithm, FRAX(r)BMI and FRAX(r)BMD assessment tools
      to determine patients for intervention.
AB  - BACKGROUND: The 2007 WHO guidelines for the treatment of osteoporosis require
      that we know the population risk of an osteoporotic fracture for each country to
      classify patients requiring treatment. MATERIAL AND METHODS: Studies have been
      carried out among a random cohort of 1,608 women over the age of 40 to assess a
      ten-year absolute risk of main osteoporotic fractures (AR-10 m.o.fx.) and hip
      fractures (AR-10 h.fx.) by using FRAX(r)BMI and FRAX(r)BMD based on the
      epidemiology of fractures in England. RESULTS: Both methods gave similar results
      in assessing the probability of fracture, showing the increase of AR-10 m.o.fx.
      in subsequent life decades to rise from 5% in the fifth decade to 25% in the
      ninth, mean result 11%, and AR-10 h.fx. to rise over the same period from 0.5% to
      13%, mean result 3%. The number of fractures increases up to the seventh and
      eighth decades, and decreases according to the number of patients in the age
      group. The commonest fracture risks reported, other than old age and low BMI,
      were a prior fracture, a family history of hip fracture and smoking. CONCLUSIONS:
      Comparative analysis of examined parameters of FRAX between people with and
      without fractures showed considerable differences only in age and AR-10 m.o.fx.
      This doubled in people with previous fractures (ca. 18% vs. 9%) and AR-10 h.fx.
      (ca. 5% vs. 2.5%). The "middle" area between the average population risks (AR-10
      m.o.fx. 11% and AR-10 h.fx. 3%) and the risks in patients with fractures (AR-10
      m.o.fx. 18% and AR-10 h.fx. 9%) could work as an indicator: below those values
      the risk is low and no treatment is required; above those values, the risk is
      high, and intervention is necessary; the middle area implies a BMD examination
      and reassessment of the fracture risk.

PMID- 21879468
TI  - Interleukin-6 and its considerable role in the pathogenesis of thyrotoxicosis
      related disturbances of bone turnover in postmenopausal women.
AB  - BACKGROUND: Thyrotoxicosis is more frequent in postmenopausal women than in the
      general population, effectively accelerating bone turnover. Interleukin-6 has
      been shown to be involved in the pathogenesis of bone disorders. Thus, the aim of
      the present study was to assess the role of IL-6 and its soluble receptor in the
      pathogenesis of thyrotoxicosis-related disturbances of bone turnover in oestrogen
      deficient women. MATERIAL AND METHODS: The study was carried out in 40 subjects
      with toxic nodular goitre in three groups: Group 1 - 13 premenopausal females,
      mean age 36 +/- 15 years (PremTx->PremEu); Group 2 - 12 postmenopausal females,
      mean age 66 +/- 14 years (PostTx->PostEu); and Group 3 - 15 males, mean age 45 +/
      21 years (MTx->MEu). Overt thyrotoxicosis and euthyreosis after treatment with
      thyrostatics were confirmed by thyrotropin, free thyroxine and free
      triiodothyronin concentrations. Serum levels of bone turnover markers: TRACP5b
      and osteocalcin as well as serum IL-6 and IL-6sR were determined using ELISA
      kits. RESULTS: TRACP5b/osteocalcin quotient was significantly elevated in the
      PostTx females compared to the PremTx women (p < 0.02). There was a positive
      correlation between serum TRACP5b and osteocalcin in the studied patients (R =
      0.45, p < 0.001). Levels of serum IL-6 values were significantly elevated in
      PostTx: 3.0 (2.14-6.40) and MTx: 2.24 (1.60-5.10), compared to PremTx females:
      1.39 (0.96-2.14) (p < 0.01 and p < 0.05 respectively). There were significant
      positive correlations between IL-6 and IL-6sR concentrations (R = 0.22, p < 0.05)
      and between IL-6sR and TRACP5b serum levels (R = 0.23, p < 0.05). CONCLUSIONS:
      The results of our study suggest that interleukin-6 plays a considerable role in
      the pathogenesis of thyrotoxicosis-related disturbances of bone turnover in
      oestrogen-deficient women.

PMID- 21879469
TI  - The association between thyroid malignancy and chronic lymphocytic thyroiditis:
      should it alter the surgical approach?
AB  - BACKGROUND: The relation between thyroid neoplasms and chronic lymphocytic
      thyroiditis (CLT) is controversial. While it is accepted that focal lymphocytic
      thyroiditis develops secondarily to malignancy, it is not clear whether diffuse
      lymphocytic thyroiditis has a tendency to develop into thyroid cancer. The aim of
      this study was to investigate the relation between CLT and malignant tumours of
      the thyroid and evaluate the surgical approach to CLT cases. MATERIAL AND
      METHODS: In this study, 917 patients operated on for thyroid diseases were
      investigated retrospectively. Seventy-seven (8.4%) patients histopathologically
      diagnosed as having CLT (either non-specific or Hashimoto's thyroiditis) were
      investigated for any concurrent malignant neoplasm. Fifteen patients in whom CLT
      and thyroid malignancy were coexisting were included in the study. RESULTS: In
      the pathological evaluation of 917 cases, malignancy in the thyroid was found in
      97 (10.6%) cases. Seventy-seven cases were categorised as CLT. Of these 77, 16
      (20.8%) were Hashimoto's thyroiditis (specific CLT) and the other 61 (79.2%) were
      non-specific CLT. In 15 cases, thyroid malignancy was found to be concurrent with
      CLT. Of the malignities, nine (60%) were papillary carcinoma, three (20%)
      medullar carcinoma, one (6.6%) follicular carcinoma, one (6.6%) Hurthle cell
      carcinoma, and one (6.6%) lymphoma. In our series, the rate of the development of
      malignancy against the background of CLT was 19.48%, while the rate in the groups
      without CLT was 9.76%, with a statistically significant difference between the
      groups (p = 0.008). CONCLUSIONS: CLT cases should be evaluated more carefully in
      terms of malignancy. If a nodule is detected on thyroiditis, the minimal surgical
      intervention should be lobectomy. Total thyroidectomy should be considered as
      preferable to subtotal thyroidectomy because of its many advantages such as
      controlling thyroiditis, removing the probability of reoperation, and hormonal
      stability.

PMID- 21879470
TI  - Intake of iodine-containing multivitamin preparations by pregnant women from the
      Krakow region of Poland.
AB  - BACKGROUND: The aim of this study was to evaluate the number of women who take
      multivitamin formulations containing iodine. MATERIAL AND METHODS: A 34-question
      questionnaire was given to 500 women during their puerperal stay in two
      obstetrics/gynaecology wards in Krakow. RESULTS: 295 pregnant women (59%) took
      iodine-containing formulations. 205 pregnant women (41%) took multivitamin
      preparations without iodine. 49.7% of the women (91 out of 183) who inhabited
      rural areas and small towns were not supplemented with iodine during pregnancy.
      Women in Krakow took iodine-containing multivitamin formulations in 61.2% of
      cases. Women with primary and secondary education did not use iodine
      supplementation in 48.3% and 50.3% of cases respectively. Women with a university
      education did not use supplementation in 38.6% of cases. The prevalence of women
      using iodine-containing multivitamin preparation was similar in each age group.
      CONCLUSIONS: The promotion of iodine supplementation to pregnant women should be
      augmented at each level of contact with medical staff. Medical staff should be
      reminded about such promotion at each level of medical care and training (general
      practitioner, obstetrics/gynaecology specialist, endocrinologist, postgraduate
      training).

PMID- 21879471
TI  - The hypertriglyceridemic waist phenotype and metabolic syndrome by differing
      criteria in type 2 diabetic patients and their relation to lipids and blood
      glucose control.
AB  - BACKGROUND: Metabolic syndrome (MetS) describes clustering of obesity,
      dyslipidemia, hyperglycemia and hypertension and increases risk for
      cardiovascular disease and type 2 diabetes. The 'hypertriglyceridemic waist'
      phenotype (HTGW) represents a simple approach to identifying individuals with
      increased risk. The aim of the study was to determine the prevalence of HTGW and
      MetS in type 2 diabetic patients, and to examine their relation to lipids and
      blood glucose control. MATERIAL AND METHODS: 300 type 2 diabetic patients were
      analysed, and their history of diabetes, anthropometric measures, measurements of
      blood pressure (BP), lipids and glycemic control parameters were taken. RESULTS:
      In type 2 diabetic patients, the prevalence of MetS was 71.0% by the AHA/NHLBI
      definition and 75.33% by the IDF definition. The prevalence was 62.58% and 66.45%
      in men, and 80% and 84.83% in women by the same definitions, respectively. There
      were 41.33% of patients with HTGW (42.76% among women and 40% among men). There
      were statistically significant differences of age, fasting plasma glucose (FPG)
      and postprandial glucose (PPG) in women with and without MetS according to both
      definitions, and of total and LDL cholesterol with and without MetS according to
      AHA/NHLBI (but not IDF). In men, there were statistically significant differences
      of total cholesterol and of HbA(1c) with and without MetS according to AHA/NHLBI
      (but not IDF). Women with HTGW had higher levels of total and LDL cholesterol,
      systolic and diastolic BP. Men with HTGW had higher levels of total cholesterol,
      diastolic BP, HbA(1c), FPG and PPG. CONCLUSIONS: Determining MetS or HTGW helps
      identify those with increased cardiovascular risk.

PMID- 21879472
TI  - Comparison of systolic and diastolic blood pressure with pulse pressure and mean
      arterial pressure for prediction of type 2 diabetes: the Isfahan Diabetes
      Prevention Study.
AB  - BACKGROUND: The aim of this study was to compare the ability of the systolic and
      diastolic blood pressure (BP), pulse pressure (PP), fraction PP (PPF) and mean
      arterial pressure (MAP) to predict progression to diabetes in non-diabetic first
      degree relatives (FDRs) of patients with type 2 diabetes. MATERIAL AND METHODS: A
      total of 701 non-diabetic FDRs aged 20-70 in 2003 to 2005 were followed through
      to 2008 for the occurrence of type 2 diabetes mellitus. At baseline and through
      follow-ups, participants underwent a standard 75 g 2-h oral glucose tolerance
      test. Prediction of progression to type 2 diabetes was assessed using area under
      the receiver-operating characteristic (ROC) curves based upon measurement of PP,
      MAP, PPF, systolic and diastolic BP. RESULTS: Diabetes developed in 72
      participants (10.3%) during the follow-up period. The incidence of type 2
      diabetes was 3.4 per 100 person years in men and 4.9 in women. Systolic and
      diastolic BP and MAP were related to diabetes, but PP and PPF were not. Systolic
      and diastolic BP and MAP have similar associations with incident diabetes. Areas
      under the ROC curves were 0.582 for systolic, 0.589 for diastolic, 0.589 for MAP,
      0.520 for PP, and 0.468 for PPF. CONCLUSION: These results indicate that systolic
      and diastolic BP are as strong as MAP in predicting progression to diabetes.
      Increased BP may help identify FDRs of patients with type 2 diabetes at high risk
      for diabetes who are candidates for BP control.

PMID- 21879473
TI  - Higher 11-beta-hydroxysteroid dehydrogenase type I gene expression in white
      adipose tissue in male than female rats.
AB  - BACKGROUND: 11-beta-hydroxysteroid dehydrogenase type I (11-beta-HSD1) in the
      white adipose tissue (WAT) of rats catalyses the conversion of 11
      dehydrocorticosterone to corticosterone, a more active glucocorticosteroid.
      Glucocorticosteroids in WAT stimulate adipocytes differentiation and increase
      adipocytes size. The aim of this study was to examine the association between
      expression of 11-beta-HSD1 in the WAT of male and female rats and adipose tissue
      mass as well as body mass. MATERIAL AND METHODS: Perirenal WAT from male and
      female Wistar rats aged three months, and ovariectomized females of the same age,
      was used in the study. 11-beta-HSD1 gene expression was assayed in the perirenal
      WAT of rats by real-time PCR. RESULTS: 11-beta-HSD1 gene expression in the
      perirenal WAT of male rats was higher than in female rats. The WAT and body mass
      of male rats was also higher than in females. 11-beta-HSD1 gene expression in the
      perirenal WAT as well as WAT mass and body mass increased simultaneously after
      ovariectomy. CONCLUSIONS: The results presented in this paper suggest that higher
      11betaHSD1 gene expression in the WAT is associated with higher body and adipose
      tissue mass. Moreover, our results suggest that oestradiol can modulate 11-beta
      HSD1 gene expression in the WAT of rats.

PMID- 21879474
TI  - Technological difficulties in ghrelin and obestatin assays.
AB  - In recent years we have performed more than 1,000 radioimmunoassays of ghrelin
      and obestatin. In these assays, we have encountered several technological
      obstacles. Another difficulty was the enormous discrepancy of plasma ghrelin
      results published by different authors. The aim of this article is to comment on
      these problems. Not all peptides of the hypothalamus and intestines are present
      in blood circulation. Several neuropeptides do not cross the blood-brain barrier,
      and several gastrointestinal peptides are present in extremely low concentrations
      in the blood. That requires time-consuming and laborious extraction. In these
      procedures, considerable amounts of peptides may be lost. In addition, these
      peptides are very unstable and prone to enzymatic degradation. This makes it
      mandatory to add enzymatic inhibitors to plasma samples. The peptides are also
      unstable in elevated temperatures, hence the assays should be performed in air
      conditioned laboratories and the kits should be transported in proper low
      temperature conditions. Peptides may appear in several isoforms of different
      biological activity, but antibodies routinely used in these assays are polyclonal
      and do not differentiate between these forms. This complicates clinical
      evaluation of the results. To date, there are no international standards of
      ghrelin, obestatin or other active peptides, probably because of their extreme
      instability. Because of technological difficulties, the results of peptide assays
      performed in different scientific research institutions vary greatly and cannot
      be compared to each other. This disadvantage may be partially diminished by
      including samples of healthy subjects in each assay run to check whether the
      peptide concentrations of the patients differ significantly from that of control
      subjects.

PMID- 21879475
TI  - The role of vitamins in the prevention and treatment of thyroid disorders.
AB  - Although vitamin deficiencies are uncommon in Poland or other developed
      countries, many patients take vitamin supplements. Despite the widespread
      availability of vitamins and the universal belief that vitamins offer health
      benefits, few publications have addressed their role in the prevention and
      treatment of thyroid diseases. There is some evidence to suggest that the
      administration of vitamins with anti-oxidant properties in patients with
      hyperthyroidism can decrease the severity of clinical symptoms, and that vitamin
      D supplementation can have a beneficial effect on the bone system for these
      patients. It has also been suggested that patients with autoimmune thyroid
      diseases should be periodically screened for vitamin B12 deficiency. There has
      been no data to support vitamin supplementation in the primary or secondary
      prevention of thyroid malignancies.

PMID- 21879476
TI  - Primary hyperparathyroidism: a rare endocrinopathy in children. Two case reports.
AB  - Primary hyperparathyroidism (PHPT) is thought to be a common disease in adults.
      However, it is a rare endocrine disorder in children and adolescents. We report
      two cases of primary hyperparathyroidism in children diagnosed at the Department
      of Endocrinology and Diabetes (EU and D) in the Children's Hospital (ChH),
      Kielce. The clinical course of the disease in these cases was fundamentally
      dissimilar, which confirms the observation that this rare endocrinopathy in
      children presents various clinical profiles, leading to diagnostic difficulties.
      In the first case, the severe course of PHPT was observed with signs suggesting a
      hypercalcemic crisis. In the second case, the patient was in a good condition
      with a mild hypercalcemia and symptoms limited to the skeleton, due to early
      identification of the disease. We believe these cases indicate the significant
      role of calcemia determination as a screening test in the diagnosis of PHPT,
      including in children.

PMID- 21879477
TI  - A difficult diagnosis: a case report of combined Riedel's disease and fibrosing
      Hashimoto's thyroiditis.
AB  - Riedel's disease (RD) is a rare form of chronic thyroiditis, predominantly
      characterised by fibrosis which may involve neighbouring tissues and organs.
      Hashimoto's disease (HD), on the other hand, is fairly common. Clinical
      differentiation between these diseases is often difficult, and the results of
      diagnostic imaging, laboratory tests and cytology studies are often similar. We
      report the case of a female patient with Riedel's thyroiditis displaying
      clinical, laboratory and radiological traits of both diseases. A 44 year-old
      Caucasian female was diagnosed with hypothyroidism. A fine-needle aspiration
      biopsy was performed; the findings were suggestive of an exacerbated chronic
      inflammatory process. However, a small lymphocyte-derived malignancy could not be
      ruled out with certainty, and so the patient was referred for elective
      thyroidectomy. The microscopic features of both specimens did not meet the
      criteria of Hashimoto's thyroiditis. The immunohistochemical studies revealed few
      scattered B lymphocytes (CD20 positive) and numerous scattered T lymphocytes (CD3
      positive). Finally, Riedel's thyroiditis with an intense inflammatory infiltrate
      composed of lymphocytes was diagnosed. Reaching a diagnosis was particularly
      difficult in this patient, since Riedel's thyroiditis, the fibrosing form of
      Hashimoto's disease and malignant tumours of the thyroid can show similar traits
      upon physical and histopathological examination. As the clinical data was
      indicative of Hashimoto's thyroiditis and there were partial histological
      criteria of two forms of thyroiditis, namely Hashimoto's and Riedel's, the very
      rare diagnosis of a combined disease was made. Dense B and T lymphocytes and some
      plasma cell infiltrates, as well as the destruction of thyroid follicles by
      fibrosis extending into surrounding tissues, were supportive of the eventual
      diagnosis. Differentiating between the histopathological and clinical
      presentation of both diseases in one patient is difficult, primarily due to the
      partial overlapping of their histopathological traits. In order to avoid a
      diagnostic error, close cooperation between the endocrinologist and pathologist
      is mandatory. It is our opinion that in our patient the two diseases existed
      separately, and their coexistence was most likely coincidental.

PMID- 21879478
TI  - Liver abscess due to Yersinia bacteremia in a well-controlled type I diabetic
      patient.
AB  - Yersiniae enterocolitica, a gram negative rod-like organism, causes terminal
      ileitis and mesenteric adenitis in adolescents and adults. Some forms present
      with liver and spleen abscesses and have worse prognosis. We report a type 1
      diabetic patient with a liver abscess mimicking metastatic liver disease who was
      successfully treated with percutaneous drainage and antibiotic administration;
      culture from blood was positive for Yersinia enterocolitica, but drainage
      material from the liver abscess did not yield a positive result for Yersinia
      enterocolitica. Although the prognosis is not good in such cases, with high
      mortality rates, our patient recovered from the disease with appropriate
      treatment.

PMID- 21879479
TI  - [Management of thyroid diseases during pregnancy].
AB  - The management of thyroid disorders during pregnancy is one of the most
      frequently disputed problems in modern endocrinology. It is widely known that
      thyroid dysfunction may result in subfertility, and, if inadequately treated
      during pregnancy, may cause obstetrical complications and influence fetal
      development. The 2007 Endocrine Society Practice Guideline endorsed with the
      participation of the Latino America Thyroid Association, the American Thyroid
      Association, the Asia and Oceania Thyroid Association and the European Thyroid
      Association, greatly contributed towards uniformity of the management of thyroid
      disorders during pregnancy and postpartum. Despite the tremendous progress in
      knowledge on the mutual influence of pregnancy and thyroid in health and disease,
      there are still important areas of uncertainty. There have been at least a few
      important studies published in the last 3 years, which influenced the thyroidal
      care of the expecting mother. It should also be remembered that guidelines may
      not always be universally applied in all populations with different ethnical,
      socio-economical, nutritional (including iodine intake) background or exposed to
      different iodine prophylaxis models. The Task Force for development of guidelines
      for thyroid dysfunction management in pregnant women was established in 2008. The
      expert group has recognized the following tasks: development of the coherent
      model of the management of thyroid dysfunction in pregnant women, identification
      of the group of women at risk of thyroid dysfunction, who may require endocrine
      care in the preconception period, during pregnancy and postpartum - that is in
      other words, the development of Polish recommendations for targeted thyroid
      disorder case finding during pregnancy, and the development of Polish trimester
      specific reference values of thyroid hormones. Comprehensive Polish guidelines
      developed by the Task Force are to systematize the management of the thyroid
      disorders in pregnant women in Poland.

PMID- 21879480
TI  - Proceedings of the First Lorenzo Tomatis Conference on Environment and Cancer.
      June 4-5, 2009, Turin, italy. Dedicated to the memory of Lorenzo Tomatis.

PMID- 21879481
TI  - Proceedings of a conference: ''From DNA-Inspired Physics to Physics-Inspired
      Biology', June 1-5, 2009, Trieste-Miramare, Italy.

PMID- 21879482
TI  - Proceedings of 14th Japanese Clinico-Pathological Conference on Renal Allograft
      Pathology. July 17, 2010, Tokyo, Japan.

PMID- 21879484
TI  - Proceedings of the Fourth International Brain-Computer Interface Meeting. May 31
      June 4, 2010, Monterey, California, USA.

PMID- 21879483
TI  - Comparison of AAV2 and AAV5 in gene transfer in the injured  spinal cord of mice.
AB  - Recombinant adeno-associated virus (AAV) vectors are promising tools for gene
      therapy. In spinal cord injury where extensive damage occurs, vectors with high
      diffusion and transduction abilities are required. We compared the diffusion
      capacity and transduction efficiency of AAV2 and AAV5 vectors using a mouse
      spinal cord injury model. Our study demonstrates that AAV5 is more effective than
      AAV2 for delivering genes into the injured spinal cord tissue. AAV5 diffused 6.9
      mm from the injection site, transduced with an approximately two-fold increase in
      total cell number and yielded an approximately three-fold increase in gene
      expression in comparison with AAV2.

PMID- 21879485
TI  - Proceedings of the 22nd International Conference on Information Processing in
      Medical Imaging. July 3-8, 2011. Kloster Irsee, Germany.

PMID- 21879486
TI  - Proceedings of the Second International Conference on Regulatory T Cells and Th17
      Cells and Clinical Application in Human Diseases. July 17-20, 2010, Shanghai,
      China.

PMID- 21879487
TI  - Special issue in honor of Henk Lekkerkerker's 65th birthday.

PMID- 21879488
TI  - Special issue in honor of Mina J. Bissel.

PMID- 21879489
TI  - Proceedings of the First Conference on Proteomics of Protein Degradation and
      Ubiquitin Pathways, June 6-8, 2010, Vancouver, British Columbia, Canada.

PMID- 21879490
TI  - Proceedings of the 9th European Symposium on Paediatric Cochlear Implantation,
      Warsaw, 2009. Preface.

PMID- 21879491
TI  - Recent pioneering cardiology developments in Japan: Japanese cardiologists have
      discovered Waon therapy for severe or refractory heart failure and extracorporeal
      cardiac shock wave therapy for severe angina pectoris.

PMID- 21879492
TI  - The endovascular stent graft raises vascular stiffness and changes cardiac
      structure within a very short time.

PMID- 21879494
TI  - Leiomyosarcoma of the temporal bone.

PMID- 21879496
TI  - "Visionary art".

PMID- 21879497
TI  - Oral Pathology Quiz #71. Case number 3. Odontogenic keratocyst.

PMID- 21879498
TI  - Oral Pathology Quiz #71. Case number 4. Pyogenic fibroma.

PMID- 21879499
TI  - Retraction. Extracellular matrix fibronectin increases prostaglandin E2 receptor
      subtype EP4 in lung carcinoma cells through multiple signaling pathways: the role
      of AP-2.

PMID- 21879501
TI  - The Finnish Cardiac Society: the history and achievements of cardiology in
      Finland are discussed by the Society's president.

PMID- 21879502
TI  - The elusive renal cell carcinoma: reversal imaging of arterial phase to improve
      acuity.

PMID- 21879503
TI  - A novel "no-touch" robot-assisted laparoscopic technique facilitates ureteral
      reconstructive surgery.

PMID- 21879504
TI  - JGA news.

PMID- 21879505
TI  - The role of education in advancing veterinary medicine.

PMID- 21879506
TI  - Pets rescued, treated  after deadly tornado.

PMID- 21879507
TI  - Herpesvirus claims  another elephant as search  for answers continues.

PMID- 21879508
TI  - Government coordinates  national response to fatal  bat disease.

PMID- 21879509
TI  - Did Irish marriage patterns survive the emigrant voyage? Irish-American
      nuptiality, 1880-1920.

PMID- 21879510
TI  - Green revolution and agro-industrialisation: a case study of primary food
      processing industries in the Indian Punjab.

PMID- 21879512
TI  - Pakistan, partition and gender: fashioning the shape of Pakistani womanhood.

PMID- 21879513
TI  - Propaganda and remembrance: gender, education, and "the women's awakening" of
      1936.

PMID- 21879514
TI  - Extraction of pacing leads: overview of current techniques.

PMID- 21879515
TI  - Abstracts of the 15th Annual Scientific Meeting of the Japanese Heart Failure
      Society (JHFS). October 13-15, 2011. Kagoshima, Japan.

PMID- 21879516
TI  - [Documenting and describing. The epistemic function of psychiatric records, their
      archiving and reinterpretation into case histories].
AB  - The paper attempts to reconstruct the writing of published case histories. Due to
      the establishment of a scientific classification system in psychiatry there were
      at the Charite several changes from the late 1870s onwards: (1) Not only was the
      documentation in the clinical records altered significantly, but also (2) the
      archive was reorganized into a double filing system and (3) the casuistic made a
      development from describing seldom or sensational cases into a mode which aimed
      to unfold psychiatric theory through 'typical cases'. Original medical records,
      the internal documentation of psychiatric observation, will be compared to their
      published version. Both, the narrative of a case study and the documentation in
      the clinical records reveal performative processes of observation and
      documentation.

PMID- 21879517
TI  - Removing the center from computing: biology's new mode of digital knowledge
      production.
AB  - This article shows how the USA's National Institutes of Health (NIH) helped to
      bring about a major shift in the way computers are used to produce knowledge and
      in the design of computers themselves as a consequence of its early 1960s efforts
      to introduce information technology to biologists. Starting in 1960 the NIH
      sought to reform the life sciences by encouraging researchers to make use of
      digital electronic computers, but despite generous federal support biologists
      generally did not embrace the new technology. Initially the blame fell on
      biologists' lack of appropriate (i.e. digital) data for computers to process.
      However, when the NIH consulted MIT computer architect Wesley Clark about this
      problem, he argued that the computer's quality as a device that was centralized
      posed an even greater challenge to potential biologist users than did the
      computer's need for digital data. Clark convinced the NIH that if the agency
      hoped to effectively computerize biology, it would need to satisfy biologists'
      experimental and institutional needs by providing them the means to use a
      computer without going to a computing center. With NIH support, Clark developed
      the 1963 Laboratory Instrument Computer (LINC), a small, real-time interactive
      computer intended to be used inside the laboratory and controlled entirely by its
      biologist users. Once built, the LINC provided a viable alternative to the 1960s
      norm of large computers housed in computing centers. As such, the LINC not only
      became popular among biologists, but also served in later decades as an important
      precursor of today's computing norm in the sciences and far beyond, the personal
      computer.

PMID- 21879518
TI  - [LONI & Co: about the epistemic specificity of digital spaces of knowledge in
      cognitive neuroscience].
AB  - In the neurosciences digital databases more and more are becoming important tools
      of data rendering and distributing. This development is due to the growing impact
      of imaging based trial design in cognitive neuroscience, including morphological
      as much as functional imaging technologies. As the case of the 'Laboratory of
      Neuro Imaging' (LONI) is showing, databases are attributed a specific
      epistemological power: Since the 1990s databasing is seen to foster the
      integration of neuroscientific data, although local regimes of data production, 
      manipulation and--interpretation are also challenging this development.
      Databasing in the neurosciences goes along with the introduction of new
      structures of integrating local data, hence establishing digital spaces of
      knowledge (epistemic spaces): At this stage, inherent norms of digital databases
      are affecting regimes of imaging-based trial design, for example clinical
      research into Alzheimer's disease.

PMID- 21879519
TI  - Sex, religion, and the single woman c.1950-75: the importance of a 'short' sexual
      revolution to the English religious crisis of the sixties.
AB  - The English 'sexual revolution' has recently become increasingly conceived as
      'long', lasting many decades, and by some historians as a gradual phenomenon, but
      reaching a peak with the introduction of the oral contraceptive pill in the
      1960s. At the same time, the 'religious crisis' of the same decade has been
      attributed by some recent scholarship to liberal Christian revolt within the
      churches, and largely unconnected with sex. This article offers different views.
      First, based on the illegitimacy rate, it argues that, after a period of decline,
      restraint, and only minor change in the period 1946-59, the 1960s witnessed a
      sudden growth in pre-marital heterosexual intercourse before the pill's
      availability to single women, implying a cultural rather than a technological
      cause. Second, based on contemporary social surveys, it argues that there is
      clear evidence of a strong inverse correlation between levels of religious
      activity and levels of pre-marital sexual intercourse. Third, it argues that in
      the 1950s the dominant conservative Christian culture restrained single women
      from pre-marital sexual intercourse, but that from the early 1960s changing
      attitudes led to rising levels of sexual activity, led by single women, which
      reduced religious attitudes and Christian churchgoing, thus constituting a
      significant instigator of the religious crisis.

PMID- 21879520
TI  - Changes in the Chinese overseas population, 1955 to 2007.
AB  - Two approaches have been adopted to study Chinese overseas. The first one
      stresses homeland ties and sojourning mentality; the second one focuses on host
      society conditions and the social construction of Chinese. This paper analyzes
      the population of Chinese overseas after the Second World War, which has
      increased steadily over time but unevenly by region from 11 million in 1955 to 39
      million in 2007. Certain historical factors and contemporary forces explain the
      uneven growth. The paper argues that undue emphasis on homeland influence is
      unwarranted in view of the importance of how receiving society and its policy of
      accommodation have shaped the growth and development of Chinese overseas
      communities after the Second World War.

PMID- 21879521
TI  - Working after childbirth: a lifecourse transition analysis of Canadian women from
      the 1970s to the 2000s.
AB  - In this paper we compare cohorts of mothers who had their first children between
      1970 and 1999, in terms of their probability of beginning work shortly after
      childbearing. Using the 2001 General Social Survey, Cycle 15 on Family History,
      we investigate the effects of women's socioeconomic characteristics on labor
      force withdrawal. Our discussion focuses on the analysis of the transition as a
      type of life course analysis. We underline the differentiation of the transition
      by cohorts, educational attainment, income, et cetera. We show that since the mid
      1980s, mothers with low educational attainment are dramatically excluded from the
      labor market within the two years following the birth of their first child.

PMID- 21879522
TI  - Masculinity, consumerism, and appearance: a look at men's hair.
AB  - Historically, being concerned about appearance was stereotypically associated
      with women. Now masculinities too have become embedded in appearance norms.
      Consequently men too are increasingly concerned about their appearance. Via
      interviews with 14 Canadian men, the role of hair in self-identification and both
      satisfaction and dissatisfaction with appearance is examined. Emergent themes
      suggest that masculinity and appearance are increasingly intertwined, and
      consumer culture cultivates a climate that encourages men to view their
      appearance as something worthy of investment. Findings suggest that men are
      concerned about their appearance-specifically their hair-and that there is a
      relationship between masculinity, appearance, and self-identification. Findings
      are discussed within theories of masculinity and consumerism.

PMID- 21879523
TI  - [The movement to represent Francophone minority groups: the future of health
      services in French].
AB  - The Action Plan for Official Languages launched in 2003 intends to revitalize the
      country's linguistic duality. Among the priority areas, health is the focus in
      order to ensure the training of health professionals to serve official language
      minority communities and to network the main actors concerned about the
      organization of services in the minority language. The aim of this paper is to
      report representations of Francophones in minority with respect to the future of
      health services in French. The study is based on a participatory methodology:
      concept mapping to identify the conceptual universe of a given problem.

PMID- 21879524
TI  - The embodied organization of a real-time fetus: the visible and the invisible in
      prenatal ultrasound examinations.
AB  - Through an analysis of videotaped interactions between healthcare professionals
      and pregnant women during ultrasound prenatal examinations in Japan, I explore
      some aspects of sequence organization in which an ultrasound real-time fetus is
      organized. The ultrasound demonstration of the fetal condition is an
      intrinsically interactional and distributed achievement. The ultrasound fetus is
      constructed as a real-time object in a particular technological environment; in
      this environment, the participants' orientations to spatially separated
      operational fields, that is, the monitor screen and the woman's abdomen, are
      exhibited and integrated in the actual course of interaction. In conclusion, the
      fundamental relation between organizational lived work in a technological
      environment and the observable features of technology will be suggested.

PMID- 21879525
TI  - Extending the rails: how research reshapes clinics.
AB  - The purpose of clinical research is to create the scientific foundation for
      medical practice. In this way of thinking, the effect on medical practice occurs
      after the research has been completed. Social studies of science have debunked
      the standard model of scientific research, observing that changes in practice
      associated with research occur not just because of the results of research but
      also because of the practice of research. Drawing on fieldwork in HIV clinics in
      the US, South Africa,Thailand, and Uganda, we argue that clinical trials shape
      medical practice by altering the organizations in which both medical treatment
      and clinical trials take place. Three general processes are central to this
      transformation: the modification of material environments, the reorganization of
      bureaucratic relations, and the prioritization of research values. These
      processes unfold somewhat differently in the clinics of poorer countries than in
      those of wealthier ones.

PMID- 21879526
TI  - Tradition and toxicity: evidential cultures in the kava safety debate.
AB  - This paper examines the debate about the safety of kava (Piper methysticum Forst.
      f, Piperaceae), a plant native to Oceania, where it has a long history of
      traditional use. Kava became popular as an anti-anxiety treatment in Western
      countries in the late 1990s, but it was subsequently banned in many places due to
      adverse reports of liver toxicity. This paper focuses on the responses to the
      bans by scientists involved in kava research, contrasting their evidential
      culture with that employed by clinicians and regulatory officials. Cultural
      constructions and social negotiations of risk are shown to be context-specific,
      and are shaped by professional, disciplinary, and organizational factors, among
      others. Though the science of hepatotoxicity is uncertain enough to allow for
      multiple interpretations of the same data, the biomedical/clinical narrative
      about kava remains dominant. This case study explores the influence of these
      cultural, social, and political factors on the production of scientific knowledge
      and the assessment of benefit/risk posed by comestibles.

PMID- 21879527
TI  - The costs and benefits of 'red tape': anti-bureaucratic structure and gender
      inequity in a science research organization.
AB  - This paper explicates a central conflict that can affect science research
      organizations, the conflict between the anti-bureaucratic stance believed to
      advance science and concerns for gender equity rooted in the universalist ethos
      of science. We present a case study of a science research organization, using
      employment and publication records, a survey of 308 employees, and qualitative
      interviews with 60 employees. We show how anti-bureaucratic organizational
      structures perpetuate gender inequities for both female scientists and non
      scientists.

PMID- 21879528
TI  - E. Leroy Ryer (1880-1972) and Elmer E. Hotaling (1887-1950), optometric leaders
      and authors, and partners in optometry practice.
AB  - E. LeRoy Ryer and Elmer E. Hotaling were very prominent optometrists of the first
      half of the twentieth century and made numerous contributions to the profession.
      They were among the early pioneers of professional optometry practice. They
      published many articles in optometry journals, and did work in instrument design.
      They were charter members of the American Academy of Optometry in 1922, Ryer
      having suggested such an organization in 1905. In the first decade of the
      twentieth century, they were briefly faculty members in a two-year optometry
      school, an unusual length of study for the time. This paper presents brief
      biographical sketches of each, along with discussion of the two books they
      coauthored, Optometric Procedure and Ophthalmometry. The former book contained
      much of their views on how optometry should be practiced.

PMID- 21879529
TI  - [Early achievements of the Danish pharmaceutical industry--3. Alfred Benzon].
AB  - The article series provides a written and pictorial account of the Danish
      pharmaceutical industry's products from their introduction until about 1950. Part
      3 deals with products from the company founded by Alfred Benzon in 1849. Alfred
      Nicolai Benzon owned the Swan Pharmacy in Copenhagen. In 1863 he started an
      independent company manufacturing branded pharmaceuticals, thus combining the
      pharmacy's activities with the wholesale business. The family owned the company
      until 1952, when it was converted into a foundation. After several restructuring
      rounds, the medicine production business continued as Benzon Pharma A/S until
      1990, when Nycomed Pharma A/S bought up all the branded pharmaceuticals. As the
      first pharmaceutical company in Denmark, Alfred Benzon was an industrial
      frontrunner in the country at the time, supplying not only the domestic market
      but foreign markets as well. Alfred Benzon was the first Danish company to
      produce ether for anesthesia, and malt extract, a dietetic preparation. The high
      quality of both products made them valuable export articles. In the early 1890s,
      Alfred Benzon became the first Danish company to start the research-based
      production of extract of thyroid glands from slaughtered cattle. This was the
      beginning of a long-standing specialization in producing organotherapeutic
      substances from animal organs originating from Danish animal husbandry. In 1932
      the company had 26 preparations of this type in its range, many of them on the
      market for several years. These medicine substances included iron preparations
      and effervescent salts followed by sulfonamides, synthetic hormones and a
      substance to counteract motion sickness.

PMID- 21879530
TI  - [A personal prescription book].
AB  - The Danish Collection of the History of Pharmacy includes a unique record: Mrs.
      I.J. Valentiner's prescription book. The slim volume dates from the period 1906
      1917 and contains a collection of 45 prescriptions for Mrs. Valentiner, whose
      husband was a land agent on a large estate, Frederikslund, on the island of
      Funen. Mrs. Valentiner's brother, Axel Bentsen, a physician in Northern Jutland
      during this period, wrote most of the prescriptions. Many of the prescriptions
      are dated within a few days of each other. The likely explanation is a practical
      one. When visiting his sister, Axel Bentsen probably provided her and her family
      with prescriptions for a broad spectrum of medicines such as analgesics, cough
      mixtures, laxatives and ointments, should they be needed. The record shows that
      various pharmacies were involved in making up 24 of the prescriptions in Mrs.
      Valentiner's prescription book until 1926, and the book was thus in use for 20
      years.

PMID- 21879531
TI  - [The formula book. The pharmacies' own formulas].
AB  - During the 19th century and part of the 20th, a book of formulas was a useful
      tool for many Danish pharmacists in their daily work in the pharmacy laboratory.
      These books were handwritten and contained formulas that supplemented the
      official formula books, e.g. the pharmacopoeias. They originated from many
      different sources such as colleagues, the pharmaceutical press, local doctors,
      veterinarians and dentists. The book of formulas could be a pharmacist's personal
      document, or it could belong to a pharmacy for general use in the laboratory. The
      formulas included many drugs, but a number of the products were intended for
      daily domestic life: ingredients for food and spirits, cosmetics, cleaning and
      maintenance, etc. Other products were for use by the local hairdresser or
      photographer, for example. The article provides an overview of 52 formula books
      in a wide variety of shapes and sizes with instructions for a total of 8,000
      10,000 compositions. Part of this large body of practical knowledge by individual
      pharmacists was collected and published in books in order to be available to all
      pharmacists. Some of this knowledge was also printed in booklets written for the
      general public under such pseudonyms as "An old Pharmacist". In the mid-20th
      century, Sven Holm enjoyed a prominent career as a well-known pharmacist giving
      advice on the radio and TV and in newspapers and magazines. The need for these
      formula books declined as pharmacies gradually stopped making up their own
      medicines towards the end of 20th century and finally ceased altogether in 1990.

PMID- 21879532
TI  - [Introduction (inquiry, status of research, sources and literature)].

PMID- 21879533
TI  - [Paraphrase. Interpretation of statements by the Vatican].

PMID- 21879534
TI  - [Documents of the Vatican. Source collection in extracts].

PMID- 21879535
TI  - Reflections on the ups and downs of optometry's relationship with organized
      medicine and organized ophthalmology.

PMID- 21879536
TI  - William Bohne (1827-1906), author of handbook for opticians, first textbook by an
      American optometrist.
AB  - William Bohne (1827-1906) was a teacher in Germany before emigrating to the
      United States in 1852. He worked as an optician (as optometrists were known at
      that time) in New Orleans in the second half of the nineteenth century. His book,
      Handbook for Opticians, which went through three editions, appears to have been
      the first optical care textbook written by an American optometrist. This paper
      gives a brief biographical sketch of Bohne and a description of the contents of
      the third edition of his book.

PMID- 21879537
TI  - How soft contact lenses came to the USA.

PMID- 21879538
TI  - Some doctors of medicine who published optometry books and played significant
      roles in early twentieth century optometric education.
AB  - This paper provides brief profiles of four doctors of medicine who wrote books
      for optometrists and who were faculty members in, and/or directors of, optometry
      schools in the early twentieth century. Those studied were Thomas G. Atkinson
      (1870-1946), Marshall B. Ketchum (1856-1937), Joseph I. Pascal (1890-1955), and
      Clarence W. Talbot (1883-1958). The content of the books they wrote is also
      discussed.

PMID- 21879539
TI  - From self-interest to selflessness. Commissioning may leave GPs straddling a
      conflict of interests.

PMID- 21879540
TI  - Antenatal. An efficient approach to maternity appointments.

PMID- 21879541
TI  - Transitional leadership. Making sure two into one does go.

PMID- 21879542
TI  - End of life care. Complying with final wishes.

PMID- 21879543
TI  - Degradations of model compounds representing some phenolics in olive mill
      wastewater via electro-Fenton and photoelectro-Fenton treatments.
AB  - The electrochemical oxidation of vanillic acid, o-coumaric acid and
      protocatechuic acid, three representative toxic phenolics in olive mill
      wastewater, was studied using carbon felt cathode in the electro-Fenton system.
      Results obtained, in the presence or absence of UV support, were compared
      throughout the degradation processes up to mineralization. It was demonstrated
      that all three phenolic compounds reacted completely with hydroxyl radicals and
      degraded efficiently. It was shown in the photoelectro-Fenton process that the
      degradation and mineralization efficiency of the phenolic compounds were enhanced
      by the effect of UV light, especially at the later stages of the degradation
      processes.

PMID- 21879544
TI  - Phosphorus recovery from human urine and anaerobically treated wastewater through
      pH adjustment and chemical precipitation.
AB  - Increased population growth and food prices have resulted in more demand for
      fertilizers, especially phosphorus (P), to be used in agriculture and production
      of food crops. This research investigated the feasibility of P recovery from
      selected wastewaters in the form of precipitates only with pH adjustment. Human
      urine and effluent of an anaerobic digester treating a piggery's wastewater were
      employed to determine appropriate pH conditions for P recovery including
      solubility of the precipitates in an agricultural soil. From the laboratory
      experiments, the highest P recovery was found to be 106 mg per one litre of urine
      at pH 11. Due to its lower P content, the highest P recovery from one litre of
      the anaerobic digester effluent was 39 mg at pH 9. The X-ray diffraction analysis
      of the precipitates identified them to consist of struvite, syn-NH4MgPO4 6H2O,
      and other precipitate compounds consisting of CaCO3, NaCl and Mg3Al2(SiO4)3 and P
      contents of the precipitate samples were found to be 3-7%. When mixed with soils
      at a moisture content of 50%, the extents of P solubilized from the precipitate
      samples were in the range of 50-60%. Application of these experimental results to
      full-scale operation for P recovery is suggested.

PMID- 21879545
TI  - Characterization and treatment of Denizli landfill leachate using anaerobic
      hybrid/aerobic CSTR systems.
AB  - Leachate generated in municipal solid waste landfill contains large amounts of
      organic and inorganic contaminants. In the scope of the study, characterization
      and anaerobic/aerobic treatability of leachate from Denizli (Turkey) Sanitary
      Landfill were investigated. Time-based fluctuations in characteristics of
      leachate were monitored during a one-year period. In characterization study;
      chemical oxygen demand (COD), biochemical oxygen demand (BOD) dissolved oxygen,
      temperature, pH, alkalinity, volatile fatty acids, total nitrogen, NH4-N,
      BOD5/COD ratio, suspended solid, inert COD, anaerobic toxicity assay and heavy
      metals concentrations in leachate were monitored. Average COD, BOD and NH4-N
      concentration in leachate were measured as 18034 mg/l, 11504 mg/l and 454 mg/l,
      respectively. Generally, pollution parameters in leachate were higher in summer
      and relatively lower in winter due to dilution by precipitation. For treatment of
      leachate, two different reactors, namely anaerobic hybrid and aerobic completely
      stirred tank reactor (CSTR) having effective volumes of 17.7 and 10.5 litres,
      respectively, were used. After 41 days of start-up period, leachate was loaded to
      hybrid reactor at 10 different organic loading rates (OLRs). OLR was increased by
      increasing COD concentrations. COD removal efficiency of hybrid reactor was
      carried out at a maximum of 91%. A percentage of 96% of residual COD was removed
      in the aerobic reactor. NH4-N removal rate in CSTR was quite high. In addition,
      high methane content was obtained as 64% in the hybrid reactor. At the end of the
      study, after 170 operation days, it can be said that the hybrid reactor and CSTR
      were very effective for leachate treatment.

PMID- 21879546
TI  - Characteristics of physicochemical adsorption of soluble matter by particles
      formed in a fluidized pellet bed reactor.
AB  - To investigate the mechanism of soluble matter removal by a fluidized pellet bed
      (FPB) reactor, an experimental study was conducted using a laboratory-scale FPB
      device for treating synthetic wastewater under a condition of no activated sludge
      seeding and no dissolved oxygen supply so that the physicochemical functions of
      the FPB reactor could be evaluated. By using polyaluminium chloride and
      polyacrylamide as coagulants, it was found that most of the substances in the
      synthetic wastewater could not be effectively removed by conventional coagulation
      and sedimentation. A similar condition was observed in the start-up period of the
      FPB operation. However, as a steady FPB was formed usually after about 10 hours'
      operation, the influent COD, ammonia nitrogen and total phosphorous could be
      quickly and effectively entrapped by the fluidized grown particle layer. Because
      these substances were not coagulable under normal conditions, adsorption might
      have performed an important role in their removal. Through an adsorption
      experiment using the grown pellets as adsorbent and glucose as adsorbate without
      dosing coagulants, it was found that the process followed well the Freundlich
      adsorption isotherm. The adsorption was also confirmed to be reversible by a
      washing experiment. A scanning electron microscopy coupled with energy dispersive
      spectroscopy analysis of the pellets before and after washing showed that the
      elements of carbon and phosphorous in the outer layer of the pellets were easily
      desorbed. The study results can provide an explanation, other than the
      coagulation mechanism, for the removal of soluble matter by the FPB.

PMID- 21879548
TI  - A correlation-regression model for the physicochemical parameters of the
      groundwater in Coimbatore city, India.
AB  - The textile hub of Coimbatore city is facing a serious water pollution problem,
      both for surface water and groundwater. Industrial and domestic waste is
      continuously discharged into surface water bodies, resulting in the degradation
      of groundwater quality. In order to assess the quality of groundwater, the
      Singanallur area was selected for the present study. The quality of groundwater
      is worse in this area and the physicochemical parameters exceed the permissible
      limits of the Indian drinking water standards. The water type of the study area
      was predominantly NaCl and MgCl. A statistical analysis was carried out to
      understand the linear relation between the best correlated parameters. The
      relationship for different parameters for the study area was analysed for two
      seasons, pre-monsoon and post-monsoon, because the water quality varies widely
      seasonally. The study showed that there is a good and equal correlation between
      total hardness and calcium, total hardness and magnesium, and calcium and
      magnesium in both time periods. The relationship can be utilized to determine the
      value of calcium and magnesium when the value of total hardness is known for the
      study area. Cluster analysis was performed to obtain a dendrogram for the study
      area, from which the source of pollution was identified for different regions.

PMID- 21879547
TI  - The decontamination of bleaching effluent by pilot-scale solar Fenton process.
AB  - A solar Fenton process was applied as post-treatment to selectively eliminate
      organic pollutants and toxicants in bleaching effluents of kraft pulp mills.
      Experiments were conducted to study the effect of system parameters (pH, initial
      concentration of H2O2, molar ratio of Fe2+/H2O2 and solar-UV irradiance) on the
      removals of chemical oxygen demand and colour. The results showed 92.8% of COD
      and 99.6% of colour were removed at pH 3.5, H2O2 30 mM/ L, Fe2+/H2O2 1:100, solar
      UV irradiance 11070 mW/m2, reaction time 120 min. The first-order kinetic model
      was used to study the dependence of the reaction rate on solar-UV irradiance: a
      linear relationship was shown to exist between reaction rate constants and solar
      UV irradiance. The results of gas chromatography mass spectrometry analysis
      showed that the toxicity of the bleaching effluents was mainly derived from the
      presence of mononuclear aromatics, polycyclic aromatic hydrocarbons and
      organochlorides, which were all degraded into harmless organic acids under the
      attack of hydroxyl radicals generated from the solar Fenton reaction.

PMID- 21879549
TI  - Modification of pineapple peel fibre with succinic anhydride for Cu2+, Cd2+ and
      Pb2+ removal from aqueous solutions.
AB  - Research on chemical modification of pineapple peel fibre with succinic anhydride
      was carried out to create a novel adsorbent for Cu2+, Cd2+ and Pb2+ removal from
      aqueous solution. After pretreatment with iso-propyl alcohol and NaOH, pineapple
      peel fibre was modified via reaction with succinic anhydride for introduction of
      carboxylic functional groups. The modified pineapple peel fibre was characterized
      with Fourier transform infrared (FTIR) spectroscopy and evaluated for its
      adsorptive ability for Cu2+, Cd2+ and Pb2+ from synthetic metal solutions. The
      FTIR analysis proved the introduction of carboxylic functional groups in the
      backbone of the modified pineapple peel fibre. The modified pineapple peel fibre
      showed higher adsorptive capacity for Cu2+, Cd2+ and Pb2+ compared with raw
      pineapple peel and pineapple peel fibre pretreated with iso-propyl alcohol. The
      adsorption of Cu2+, Cd2+ and Pb2+ on the modified pineapple peel fibre depended
      on solution pH value, adsorption time and initial metal concentration. The
      maximum adsorption capacities of the modified fibre were observed at pH 5.4 for
      Cu2+ (27.68 +/- 0.83 mg g(-1) or 0.44 mmol g(-1)), at pH 7.5 for Cd2+ (34.18 +/-
      1.02 mg g(-1) or 0.30 mmol g(-1)) and at pH 5.6 for Pb2+ (70.29 +/- 2.11 mg g(-1)
      or 0.34 mmol g(-1)) respectively. The adsorption followed the pseudo-second-order
      kinetics model and the experimental data coincided well with the Langmuir model.

PMID- 21879550
TI  - The effects of antecedent dry days on the nitrogen removal in layered soil
      infiltration systems for storm run-off control.
AB  - The effects of antecedent dry days (ADD) on nitrogen removal efficiency were
      investigated in soil infiltration systems, with three distinguishable layers:
      mulch layer (ML), coarse soil layer (CSL) and fine soil layer (FSL). Two sets of
      lab-scale columns with loamy CSL (C1) and sandy CSL (C2) were dosed with
      synthetic run-off, carrying chemical oxygen demand of 100 mg L(-1) and total
      nitrogen of 13 mg L(-1). The intermittent dosing cycle was stepwise adjusted for
      5, 10 and 20 days. The influent ammonium and organic nitrogen were adsorbed to
      the entire depth in C1, while dominantly to the FSL in C2. In both columns, the
      effluent ammonium concentration increased while the organic nitrogen
      concentration decreased, as ADD increased from 5 to 20 days. The effluent of C1
      always showed nitrate concentration exceeding influent, caused by nitrification,
      by increasing amounts as ADD increased. However, the wash-out of nitrate in C1
      was not distinct in terms of mass since the effluent flow rate was only 25% of
      the influent. In contrast, efficient reduction (>95%) of nitrate loading was
      observed in C2 under ADD of 5 and 10 days, because of insignificant nitrification
      in the CSL and denitrification in the FSL. However, for the ADD of 20 days, a
      significant nitrate wash-out appeared in C2 as well, possibly because of the re
      aeration by the decreasing water content in the FSL. Consequently, the total
      nitrogen load escaping with the effluent was always smaller in C2, supporting the
      effectiveness of sandy CSL over loamy FSL for nitrogen removal under various
      ADDs.

PMID- 21879551
TI  - Measurement and modelling of adsorption equilibrium, adsorption kinetics and
      breakthrough curve of toluene at very low concentrations on to activated carbon.
AB  - Indoor air pollution, characterized by many pollutants at very low
      concentrations, is nowadays known as a worrying problem for human health. Among
      physical treatments, adsorption is a widely used process, since porous materials
      offer high capacity for volatile organic chemicals. However, there are few
      studies in the literature that deal with adsorption as an indoor air pollution
      treatment. The aim of this study was to investigate the adsorption of toluene on
      to activated carbon at characteristic indoor air concentrations. Firstly, global
      kinetic parameters were determined by fitting Thomas's model to experimental data
      obtained with batch experiments. Then, these kinetic parameters led to the
      determination of Henry's coefficient, which was checked with experimental data of
      the adsorption isotherm. Secondly, we simulated a breakthrough curve made at an
      inlet concentration 10 times higher than the indoor air level. Even if the
      kinetic parameters in this experiment are different from those in batch
      experiments, it can be emphasized that the Henry coefficient stays the same.

PMID- 21879552
TI  - Characterization and metal availability of copper, lead, antimony and zinc
      contamination at four Canadian small arms firing ranges.
AB  - Backstop soils of four small-arms firing ranges (SAFRs) of the Canadian Force
      Bases (CFBs) were characterized in terms of their total soil Cu, Pb, Sb and Zn
      concentrations, grain size distribution, mineralogy, chemical properties,
      vertical in-depth contamination distribution (for one CFB), and scanning electron
      microscope (SEM-EDS) characterization. Metal availability from the soils was
      evaluated with three leaching tests: the toxicity characteristics leaching
      procedure (TCLP), representing a landfill leachate; the synthetic precipitation
      leaching procedure (SPLP), representing field conditions; and the gastric juice
      simulation test (GJST), representing the leachate of the human stomach during the
      digestive process and, therefore, the potential metal transfer to humans in the
      case of soil ingestion. Metal analyses of soils and leaching test extracts were
      conducted with an Inductively Coupled Plasma Atomic Emission Spectrometry (ICP
      AES) instrument. Total soil results showed maximal concentrations of 27,100 mg/kg
      for Pb, 7720 mg/kg for Cu, 1080 mg/kg for Zn, and 570 mg/kg for Sb. The SEM-EDS
      analysis showed significant amounts of lead carbonates, which resulted from the
      alteration of the initial metallic Pb particles. Metal availability evaluation
      with the leaching tests showed that TCLP Pb and Sb thresholds were exceeded. For
      the SPLP and the GJST, the drinking water thresholds of the Ministere du
      Developpement Durable, de l'Environnement et des Pares (MDDEP) of Quebec were
      exceeded by Pb and Sb. The metal availability assessment showed that SAFR
      backstop soils may pose a potential risk to the environment, groundwater and
      humans, and affect the management of such soils in order to minimize potential
      metal dispersion in the environment.

PMID- 21879553
TI  - Removal and recovery of nutrients as struvite from anaerobic digestion residues
      of poultry manure.
AB  - The removal and the recovery of nutrients, namely nitrogen (N) and phosphorus (P)
      from anaerobically digested and solid-liquid separated manure effluents via
      struvite precipitation were investigated. Both the liquid and the solid phases of
      the poultry manure digester effluent were subjected to struvite precipitation
      experiments. The Mg:N:P molar ratio of 1:1:1 in the liquid phase resulted in an
      average NH4-N removal efficiency of 86.4%, which increased to 97.4% by adjusting
      the Mg:N:P ratio to 1.5:1:1. The acidic phosphorus-dissolution process was
      applied to the solid phase of the effluent to obtain a phosphorus-enriched
      solution. Nutrient recovery experiments with NaOH as the buffering reagent were
      conducted with and without addition of external chemicals (Mg and P sources) to
      evaluate the influence of the Mg:N:P molar ratio, the Mg:P molar ratio and pH.
      All the experiments depicted complete PO4-P (99.6-100.0%) and partial NH4-N (3.3
      65.6%) recoveries from the phosphorus-enriched solution.

PMID- 21879554
TI  - Assessment of a full-scale duckweed pond system for septage treatment.
AB  - Environmental conditions and wastewater treatment performance in a full-scale
      duckweed pond system are presented. The treatment system consisted of three
      stabilization ponds in series and was fed with septage. Vacuum trucks pumped the
      septage from residential holding tanks and discharged it to the system daily. The
      inflow rates averaged 36 m3 d(-1) in the cold season and 60 m3 d(-1) in the warm
      season. Duckweed (Lemna minor) colonized the ponds in the warm months and
      survived during the cold season. Because of the difficult process for harvesting
      the duckweed biomass, the investigation of the treatment efficiency was carried
      out without plant harvesting. Samples were collected from the vacuum trucks and
      from the exit of each pond and were analysed for physicochemical and
      microbiological parameters over a period of 12 months. The results showed that
      the duckweed mat suppressed algal biomass, which in turn led to anoxic and
      neutral pond conditions. On an annual basis, the duckweed system sufficiently
      removed BOD5 (94%), NH4+ (72%) and E. coli (99.65%), with lower removal of TSS
      (63%) and Enterococci (91.76%). A slight increase (1.1%) was recorded for o-PO4(3
      ). Between the two sampling seasons, BOD5 and TSS removal efficiencies were
      higher in the cold season with the longer retention time. Similar removal values
      in the warm and the cold season were found for nutrients and bacteria. These
      findings indicate that BOD5 and TSS removals are less temperature-dependent at
      higher retention times, while ammonia nitrogen and bacterial removals are
      substantially influenced by temperature as well as retention time.

PMID- 21879555
TI  - The effect of the presence of metatartaric acid on removal effectiveness of heavy
      metal ions on chelating ion exchangers.
AB  - The paper presents experimental results and their evaluation for the sorption of
      copper(II), zinc(II), cobalt(II) and nickel(II) complexes with metatartaric acid
      on chelating ion exchangers with different functional groups. The literature
      lacks the data concerning sorption of heavy metal ions in the presence of
      metatartaric acid on ion exchangers. The effect of important parameters such as
      the value of pH, the metal(II) ion and ligand concentration as well as their
      molar ratio and the type of functional group of the ion exchanger used was
      studied. It was found that the time of 60 min was sufficient for sorption to
      attain equilibrium. The equilibrium sorption capacities for copper(II), zinc(II),
      cobalt(II) and nickel(II) complexes with metatartaric acid were 37.35 mg/g, 32.02
      mg/g, 32.78 mg/g and 28.31 mg/g on Lewatit TP 207 and 42.15 mg/g, 34.32 mg/g,
      27.76 mg/g and 21.70 mg/g on Lewatit TP 260, respectively. The sorption optimum
      pH was 7. Temperature does not affect the sorption process significantly. The
      sorption data were well fitted by the Langmuir adsorption model whereas kinetics
      of the sorption process was well described by the pseudo second order kinetics
      equation.

PMID- 21879556
TI  - Recovery of metallic copper by integrated chemical reduction and high gradient
      magnetic separation.
AB  - The recovery of metals from waste effluents is necessary for pollution prevention
      and sustainable practice. High gradient magnetic separation (HGMS) is seen as a
      viable method. We investigated the capture of valence copper from aqueous copper
      ion by HGMS in combination with a chemical reduction process. When a copper
      solution (3.9 or 15.6 mM) was exposed to excess of dithionite (mole ratio of 1:3)
      in the presence of ammonia (mole ratio of 4) and amended with MnCl2 (2.5 g/L) and
      the mixture passed through a flow reactor under a strong magnetic field (10000
      Gauss), valence copper was obtained and captured in the reactor with well over
      95% yields. The chemical reduction reactions were unaffected by the presence of
      MnCl2 while the amount of MnCl2 (0, 20 and 32 mM) has significantly varied the
      copper recovery efficiency, especially in the case of high initial copper ion
      concentration (15.6 mM). Formation of MnO2 flocs was found to have a detrimental
      effect on copper removal efficiency. The HGMS method offers a tool of resource
      recovery for copper from waste effluents.

PMID- 21879557
TI  - Thin wetted film cylindrical flow photo reactor for the degradation of Procion
      blue H-B dye over TiO2 and ZnO.
AB  - A thin wetted film cylindrical flow reactor was fabricated for photocatalytic
      oxidation of Procion blue H-B dye in textile washwater with the suspensions of
      TiO2 and ZnO. The disappearance of colour and organic reduction were studied in
      terms of the removal of colour and chemical oxygen demand (COD). Operating
      parameters such as effect of pH, UV irradiation with and without catalyst,
      initial concentration of dye and effect of flow rate were studied and kinetics of
      Procion blue H-B dye has been studied over TiO2 and ZnO surfaces. Since
      adsorption is the prerequisite condition for decolorization/degradation of dye
      molecules in the presence of heterogeneous catalysis, the Langmuir and Freundlich
      isotherms were examined to verify the adsorption intensity. The results clearly
      demonstrated that, the optimum loading of the photocatalyst was found to be 300
      and 400 mg/L of TiO2 and ZnO, respectively. The maximum COD reduction efficiency
      was 68% for TiO2 and 58% for ZnO. On the other hand, the colour removal
      efficiency was found to be 74% and 69%, respectively for TiO2- and ZnO-assisted
      systems under optimum conditions. Conclusively, these two semiconductors could
      degrade Procion blue H-B dye at different time intervals and both isotherms fit
      well.

PMID- 21879558
TI  - Nitrification of an industrial wastewater in a moving-bed biofilm reactor: effect
      of salt concentration.
AB  - Nitrification of wastewaters from chemical industries can pose some challenges
      due to the presence of inhibitory compounds. Some wastewaters, besides their
      organic complexity present variable levels of salt concentration. In order to
      investigate the effect of salt (NaCl) content on the nitrification of a
      conventional biologically treated industrial wastewater, a bench scale moving-bed
      biofilm reactor was operated on a sequencing batch mode. The wastewater
      presenting a chloride content of 0.05 g l(-1) was supplemented with NaCl up to 12
      g Cl(-) l(-1). The reactor operation cycle was: filling (5 min), aeration (12 or
      24h), settling (5 min) and drawing (5 min). Each experimental run was conducted
      for 3 to 6 months to address problems related to the inherent wastewater
      variability and process stabilization. A PLC system assured automatic operation
      and control of the pertinent process variables. Data obtained from selected batch
      experiments were adjusted by a kinetic model, which considered ammonia, nitrite
      and nitrate variations. The average performance results indicated that
      nitrification efficiency was not influenced by chloride content in the range of
      0.05 to 6 g Cl(-) l(-1) and remained around 90%. When the chloride content was 12
      g Cl(-) l(-1), a significant drop in the nitrification efficiency was observed,
      even operating with a reaction period of 24 h. Also, a negative effect of the
      wastewater organic matter content on nitrification efficiency was observed, which
      was probably caused by growth of heterotrophs in detriment of autotrophs and
      nitrification inhibition by residual chemicals.

PMID- 21879559
TI  - Persistence of non-native spore forming bacteria in drinking water biofilm and
      evaluation of decontamination methods.
AB  - Persistence of Bacillus globigii spores, a surrogate for Bacillus anthracis, was
      studied on biofouled concrete-lined slides in drinking water using biofilm
      annular reactors. Reactors were inoculated with B. globigii spores and
      persistence was monitored in the bulk and biofilm phases, first in dechlorinated
      water and later with free chlorine concentrations of 1 and 5 mg/L. In the
      dechlorinated study, a steady state population of spores developed on the slides.
      The addition of free chlorine at 5 mg/L decreased the adhered spore density by 2
      logs within 4 hours and spores were not detected after 67 and 49 hours in the
      presence of 1 and 5 mg/L free chlorine, respectively. This suggests that adhered
      spores can persist in non-chlorinated conditions, but detach and/or are
      inactivated upon addition of free chlorine. When injected into a chlorinated
      reactor, adhered spore density continually decreased and spores were either
      undetectable or unquantifiable by 48 hours for both 1 and 5 mg/L chlorine
      concentrations. Results from these experiments suggest that the presence of a
      free chlorine residual limits adherence of viable spores to biofouled concrete
      lined pipe walls by inactivating spores before they have attached. Both free
      chlorine concentrations (1 and 5 mg/L) were equally effective at inactivating
      spores in terms of log reduction, but the higher concentrations yielded faster
      rates of log reduction.

PMID- 21879560
TI  - Full-scale sludge liquor treatment for ammonium reduction with low carbon dosage.
AB  - The separate treatment of sludge liquor, produced by dewatering anaerobic
      digested sludge at wastewater treatment plants, gives rise to extreme
      environments for nitrogen removal. A full-scale sequencing batch reactor was
      operated with the aim of introducing and studying denitritation as a supplement
      to nitritation in order to reduce operating costs. Since the main plant only has
      problems with ammonium reduction capacity, the initial strategy was to have
      sufficient ammonium reduction with optimal alkalinity production by denitrifiers,
      i.e. low carbon dosage and minimum alkalinity and residual oxidized ammonium in
      the effluent. This strategy led to an unbalanced and sensitive process because
      the denitrifiers were often inhibited. High dissolved oxygen (DO) readings and no
      decrease in oxidation-reduction potential (ORP) during anoxic phases with
      simultaneous ethanol dosage indicated inhibition of denitrifiers, probably by the
      intermediate product NO, which may have interfered with the DO sensor. Nitric
      oxide production was believed to be favoured in the beginning of the anoxic phase
      as a result of low pH and high nitrite concentration. A stable nitritation
      denitritation process could be achieved when the aerobic hydraulic retention time
      (HRT) was decreased to the same length as the anoxic HRT, which resulted in
      increased unused alkalinity.

PMID- 21879561
TI  - Efficiency of hydroxyl radical formation and phenol decomposition using UV light
      emitting diodes and H2O2.
AB  - A novel process combining hydrogen peroxide (H2O2) and radiation emitted by
      ultraviolet light emitting diodes (UV LEDs) has been investigated. The UV LEDs
      were used as UV-C light sources emitting radiation in the range 257-277 nm for
      decomposition of the model substance phenol in water. In addition, the effect of
      H2O2 to phenol molar ratio and initial phenol concentration was examined. Two
      parameters, the decomposition efficiency of phenol and characterization of
      hydroxyl radical (HO*) production from H2O2 when illuminated with UV radiation,
      were selected to provide detailed information regarding the performance of the UV
      LEDs in the treatment process. A new concept was introduced to characterize and
      describe the production of HO* radicals produced when photons were absorbed by
      H2O2 molecules. The phenol decomposition efficiency at the initial concentration
      of 100 mg/L was the most pronounced at the lowest emitted wavelength. A
      significant correlation was found between the phenol decomposition efficiency and
      the photons absorbed by H2O2 (i.e. formation of radicals).

PMID- 21879562
TI  - Experimental investigation of an applicator of liquid slurry, from biogas
      production, for crop production.
AB  - A unit for the application of liquid digested slurry in the field was designed
      and developed. The developed slurry applicator had a capacity of 1500 L and was
      pulled by a 35 h.p. tractor. The liquid digested slurry of a biogas plant was
      pumped in to the tank with the help of a slurry pump. The necessary power
      transmission system, consisting of a pulley, power take off shaft (PTO) and cross
      joints, was provided to get power from the PTO of the tractor. In this paper an
      attempt has been made to evaluate the application of liquid slurry in the field
      in terms of plant growth parameters such as number of branches/plant, number of
      nodules/plant, plant height and yield attributes like pods/plant and grains/pod.
      The application of liquid slurry resulted in an increase in grain, straw and
      biological yields of 32%, 7% and 15%, respectively, compared with the application
      of farmyard manure.

PMID- 21879563
TI  - Remediation of soils contaminated with chromium using citric and hydrochloric
      acids: the role of chromium fractionation in chromium leaching.
AB  - Acid washing is a common method for soil remediation, but is not always efficient
      for chromium-contaminated soil. Both soil particle size and the forms of chromium
      existing in the soil affect the efficiency of soil washing. Laboratory batch and
      column dissolution experiments were conducted to determine the efficiencies of
      citric and hydrochloric acids as agents to extract chromium from soils
      contaminated with chromium. The effects of soil particle size and chromium
      fractionation on Cr leaching were also investigated. About 90% of chromium in the
      studied soil existed either in residual form or bound to iron and manganese
      oxides, and Cr fraction distributions were similar for all soil particle sizes.
      Almost all exchangeable and carbonate-bound chromium was removed by washing once
      with 0.5 M HCl, whereas organic chromium was more effectively removed by washing
      with citric acid rather than with HCl solution of the same concentration. For
      chromium fractions that were either bound to Fe-Mn oxides or existed as residual
      forms, the efficiencies of acid washing were usually 20% or less, except for 0.5
      M HCl solution, which had much higher efficiencies. Separation of the soil sample
      by particle size before the separate washing of the soil fractions had little
      improvement on the chromium removal.

PMID- 21879564
TI  - The effects of H2O and SO2 on the behaviour of CuSO4-CeO2/TS for low temperature
      catalytic reduction of NO with NH3.
AB  - The catalyst CuSO4-CeO2/TiO2-SiO2 (CuSO4-CeO2/TS), for low temperature catalytic
      reduction (LT-SCR) of NO with NH was prepared by the impregnation method. The
      impacts of H2O and SO2 on the catalyst were investigated. Experiments showed that
      H2O brought down the catalyst's activity at low reaction temperature. However,
      this negative effect of H2O could be mostly eliminated with a raised temperature
      of above 220 degrees C. In a 10-hour experiment on the catalyst's resistibility
      to SO2 poisoning, NO conversion increased slightly by the promoting effect of
      SO2. The same catalyst underwent continuous examination with both SO2 and H2O in
      the feed gas; NO conversion of around 90.2% was maintained for 37 hours, showing
      better performance than CuSO4-CeO2/TiO2. This suggested that SiO2 in the TiO2
      SiO2 catalyst supported the supression of the oxidization of SO2 to SO3.
      Therefore, the formation of ammonium sulphate over the catalyst and the
      sulphation of CeO2 in the catalyst were greatly alleviated, leading to a better
      resistibility of the catalyst to SO2 poisioning. After the 37 hours, the catalyst
      activity began to fall, and an irrecoverable deactivation of the catalyst was
      observed.

PMID- 21879565
TI  - Biofouling characteristics and identification of preponderant bacteria at
      different nutrient levels in batch tests of a recirculating cooling water system.
AB  - Understanding the influence of nutrient levels on biofouling control is an
      important requirement for management strategies in a recirculating cooling water
      system. Nutrient limitation may be one way to control biofouling development
      without increasing biocide dosing. Therefore, this study was carried out to
      investigate the effects of nutrient levels on biofouling characteristics and to
      identify the preponderant bacteria in the batch tests with a simulated cooling
      water system. The biofouling characteristics were assessed by varying the
      biofoulant mass and the bacteria respiratory activity, which was estimated by
      measuring oxygen uptake rates. According to the results obtained in nutrient
      factor experiments, the biofouling could be better controlled at carbon, nitrogen
      and phosphorus concentrations of 30 mg N/L, 8 mg N/L and 1.0 mg P/L,
      respectively. Increasing carbon concentrations shortened the biofouling initial
      growth period and resulted in higher biofoulant mass. The preponderant bacteria
      strains involved in biofouling under two culture conditions were identified by
      applying both physiological and biochemical tests and further molecular biology
      techniques with phylogenetic affiliation analysis. Enterobacter (family
      Enterobacteriaceae), Staphylococcus (family Micrococcaceae), Bacillus (family
      Bacillaceae), Proteus (family Enterobacteriaceae), Neisseria (family
      Neisseriaceae) and Pseudomonas (family Pseudomonadaceae) were dominant in the
      conditions of lower carbon concentration (30 mg/L). Enterobacter are autotrophs,
      but the other five bacteria are all heterotrophs. In the conditions of higher
      carbon concentration (70 mg/L), Klebsiella (family Enterobacteriaceae),
      Enterobacter and Microbacterium (family Microbacteriaceae) were dominant;
      Enterobacter and Microbacterium are heterotrophs.

PMID- 21879566
TI  - Preparation, morphology and coagulation characteristics of a new polyferric
      chloride coagulant prepared using pyrite cinders.
AB  - Pyrite cinders are the main industrial waste generated from the process of
      sulphuric acid production using pyrite ores. The pyrite cinders may have
      utilization value in preparing a new polyferric chloride (PFC) coagulant. In
      order to attain this objective, a preparation method for PFC products from pyrite
      cinders was studied by a Taguchi orthogonal array experiment. On the basis of the
      successful preparation, the morphologies and coagulation characteristics of three
      PFC products, with different basicities, were observed by transmission electron
      microscopy (TEM) and examined by jar tests, respectively. The results showed that
      the molar ratio of NaOH to Fe should be in a range between 0.75:1 and 1:1, the
      molar ratio of stabilizer NaH2PO4 to Fe should be in a range between 0.12:1 and
      0.15:1, the curing time should be 2 h, the curing temperature can be 60 degrees C
      and the molar ratio of NaHCO3 to Fe can be determined according to the basicity
      required in order to get the optimal stability of PFC products and the best
      flocculation efficiency. Although the degree of aggregation of the PFC products
      became larger with the increase in the basicity, the coagulation efficiency could
      be only improved with an increase in the basicity within a certain range. When
      the basicity exceeded a certain value, the coagulation efficiency started to
      decrease. In this study, PFC2 (B = 11.16%) had better coagulation characteristics
      than either PFCl (B = 6.08%), PFC2 (B = 11.16%), PFC3 (B = 15.92%) or
      polyaluminium chloride (PAC).

PMID- 21879567
TI  - Night-mare and its treatment.

PMID- 21879568
TI  - The treatment of tuberculosis in Ferrara (Italy) in the 19th century.
AB  - The present work is a review of the remedies in use in Ferrara against
      tuberculosis in the 1800s. The work started from the discovery of accounts
      describing methods and remedies. These remedies were also in use world wide. Of
      particular interest is the work by Antonio Campana, a famous professor of
      Pharmaceutical Chemistry and Botany in Ferrara, who wrote a pharmacopoeia which
      had several editions between 1797 and 1841. The Farmacopea Ferrarese was
      addressed to the apothecaries of Ferrara. Nevertheless, due to its great
      reputation it had an international distribution. It provided us with an
      exhaustive view about the medical field in Ferrara in the early 1800s. The
      remedies adopted in the city in the second half of the century were in line with
      those present abroad. The work was also supported by the discovery of statistical
      accounts of the Sant'Anna hospital from 1871. The manuscript written by
      Alessandro Bennati enabled elucidation of the methods used to treat tuberculosis
      in the second half of the century. Bennati's work is an historical document
      completed by the work of the physician Cesare Minerbi.

PMID- 21879569
TI  - Ingenious pharmaceutical historical objects through social scientific spectacles.

PMID- 21879570
TI  - Regulations introduced in Scottish cities during the fourteenth to the
      seventeenth centuries to prevent the spread of the plague.

PMID- 21879571
TI  - The seaman's medicine chest in the late 18th century.

PMID- 21879572
TI  - Black eye cosmetics of ancient Egypt.

PMID- 21879573
TI  - Charles W. White and Walter White: colonial commercial travellers.

PMID- 21879574
TI  - The mental health sector and the social sciences in post-World War II USA. Part
      I: total war and its aftermath .
AB  - This paper examines the impact ofWorldWar II and its aftermath on the mental
      health sector, and traces the resulting transformations in US psychiatry and
      psychology. Focusing on the years between 1940 and 1970, it analyses the growing
      federal role in funding training and research in the mental health sector, the
      dominance of psychoanalysis within psychiatry in these years, and the parallel
      changes that occurred in both academic and clinical psychology.

PMID- 21879575
TI  - From social pathologies to individual psyches: psychiatry navigating socio
      political currents in 20th-century Latvia.
AB  - The paper explores psychiatry's responses to the twentieth-century socio
      political currents in Latvia by focusing on social objectives, clinical
      ideologies, and institutional contexts of Soviet mental health care. The
      tradition of German biological psychiatry in which Baltic psychiatrists had been
      trained blended well with the materialistic monism of Soviet psychoneurology.
      Pavlov's teaching of the second signal system was well suited to Soviet
      ideological needs: speech stimuli were seen as a vehicle for moulding the
      individual's mind. The transformation in diagnostic practices during the 1970s
      and 1980s reflected the demise of optimism about the capacity of the self to
      model itself to the needs of the society. Latvian psychiatry was prepared to
      embrace more individualistic and pessimistic theories of the self.

PMID- 21879576
TI  - 'Good in all respects': appearance and dress at Staffordshire County Lunatic
      Asylum, 1818-54.
AB  - Dress was integral to the ideals and practice of Staffordshire County Lunatic
      Asylum, an institution catering for all social classes. Lunatics' appearance was
      used to gauge the standard of care inside the asylum and beyond. Clothing was
      essential for moral treatment and physical health. It helped to denote social and
      institutional class: clothes were integral to paupers' admission; rich patients
      spent time and money dressing; for disturbed inmates and those who destroyed
      asylum attire, the consequence could be'secure dress', which was fundamental to
      therapeutics. Later, when an ethos of non-restraint was introduced, the
      superintendent used patients' appearance to propagate an image of his enlightened
      care.

PMID- 21879577
TI  - Sexuality and psychoanalytic aggrandisement: Freud's 1908 theory of cultural
      history.
AB  - In 1908, in his article "'Civilized" sexual morality and modern nervous illness',
      Freud presented neuroses as the consequence of a restrictive state of cultural
      development and its 'civilized morality'. He found the inspiration for this idea
      by expanding upon previous formulations in this area by his predecessors (notably
      Christian von Ehrenfels) that focused on a cultural process earlier introduced by
      Kant, while also integrating in his analysis the principles of Haeckel's
      evolutionism (history of development, recapitulation) which eventually re-defined
      the psychoanalytic theory of neuroses. These new theoretical elements became the
      basis of psychoanalytic theory and thereby influenced subsequent thinking in the
      cultural process itself and in human sciences. This transformation of underlying
      theory provided a unique historical and analytical framework for psychoanalysis
      which allowed Freud to claim for it a pre-eminent position among the human
      sciences.

PMID- 21879579
TI  - Vitamins for the soul: John Bowlby's thesis of maternal deprivation, biomedical
      metaphors and the deficiency model of disease.
AB  - In 1951 John Bowlby, British psychoanalyst and child psychiatrist, published his
      now famous report, Maternal Care and Mental Health, commissioned by the World
      Health Organization. In this report, Bowlby coined the term 'maternal
      deprivation', which quickly permeated into Western psychiatry and psychology. The
      implications of Bowlby's writings, while widely criticized and contested,
      generated a considerable amount of research and brought about significant changes
      in perceptions of separation between children and their mothers. This article
      examines the origins of the 'maternal deprivation' hypothesis, focusing on how
      the deficiency theory of disease influenced psychiatric discourse, and framed
      Bowlby's theory of maternal care. We argue that developments in paediatric
      medicine, and particularly in the field of nutritional deficiencies, provided
      Bowlby a prototype for conceptualizing his early views on the psychological needs
      of children and the development of psychopathology.

PMID- 21879578
TI  - Infanticide in Mecklenburg and Western Pomerania: documents from four centuries
      (1570-1842).
AB  - In this study we present an unprecedented comprehensive overview of cases of
      infanticide in the region of Mecklenburg-Western Pomerania, from the end of the
      16th century to the middle of the 19th century. Using the Faculty of Law's
      verdict files stored in the University of Rostock's archives, we analysed and
      evaluated 362 cases. Changes in the prosecution of this crime, in the way the
      trials were conducted and in the passing of sentences illustrate the judicial
      conceptions of the academics, as well as being of great social interest. For the
      almost exclusively female defendants, behavioural patterns occurred repeatedly:
      shame, confusion and hopelessness triggered concealment of the pregnancy and
      ultimately the deliberate or negligent killing of the newborn child.

PMID- 21879580
TI  - 'On periodical depressions and their pathogenesis' by Carl Lange (1886).
AB  - Carl Lange was the founding father of neurology in Denmark, authoring several
      pioneering works within this field; however, these remained largely unknown
      internationally as he did not have them translated into a major language. He
      became a pioneer of psychophysiology with his contribution to the so-called James
      Lange theory of emotion. His treatise on'periodical depressions' ('the Lange
      theory of depressions', 1886), is not only an early historical landmark but also
      a masterly 'modern' description concerning the nosology and nosography of
      recurrent depressions. Moreover, it is a landmark in the early history of lithium
      therapy, sadly ignored by Lange's contemporaries, but which little more than half
      a century later, with Cade's rediscovery of lithium's therapeutic effect in mood
      disorders in 1949, ushered in modern psychopharmacology.

PMID- 21879581
TI  - From war service to domestic service: ex-servicewomen and the Free Passage Scheme
      1919-22.
AB  - At the end of the First World War, the British government put into operation a
      Free Passage Scheme for ex-servicemen, ex-servicewomen and their dependants to
      emigrate to the colonies and dominions of the Empire. This scheme was driven by a
      complex network of interlinked beliefs and policies concerning both the
      relationship between the metropole and the Empire, and the perceived necessity
      for social stability in Britain and in the dominions and colonies. This article
      examines the Free Passage Scheme, paying particular attention to the ways in
      which it was envisaged as a means of restoring a gendered balance of the
      population in Britain, where young women outnumbered young men at the end of the
      war, and in the dominions, where men outnumbered women, and was also seen as a
      way of emigrating women whose wartime work experiences were understood to be in
      conflict with gendered identities in the post-war period. The article argues that
      the Free Passage Scheme needs to be understood as gendered, as it envisaged the
      transformation of female members of the auxiliary wartime services into domestic
      servants for the Dominions. The scheme's failure, it is argued, prefigures the
      failure of the far larger Empire Settlement Act of 1922 to emigrate large numbers
      of British women as domestic servants.

PMID- 21879583
TI  - The forgotten survey: social services in the Oxford district: 1935-40.
AB  - This article describes one of the lesser known social surveys of the first half
      of the twentieth century in Britain and looks at its origins and its outcomes.
      Funded by the Rockefeller grant to Oxford University to enhance social studies
      there, the Oxford Survey published in two volumes in 1938 and 1940 engaged Oxford
      academics from agricultural economics, economics, statistics, and government, as
      well as Barnett House members involved in voluntary organizations, adult
      education, settlements, citizenship, and social work. It was a far-reaching study
      that aimed to analyse all aspects of public services, in the context of a
      thorough-going description of the geography, industry, and population statistics
      of the local area. It was also designed to have national relevance, because of
      the development of the motor industry in Cowley. The Oxford Survey differed from
      Booth and Rowntree's exploration of the habits and circumstances of the urban
      poor. Instead, it had more affinity to surveys of industrial and regional
      planning and work coming from the Le Play school, in which the act of surveying
      communities was perceived as a way of enhancing citizenship.

PMID- 21879582
TI  - Youth crime and preventive policing in post-war Scotland (c.1945-71).
AB  - This article explores debates concerning the methods and styles used by the
      police service in its dealings with children and young people in post-war
      Scotland (in comparison with England). Study of the implementation of Police
      Juvenile Liaison Schemes is used to consider shifting points of tension as well
      as cooperation between the police and other occupational groups engaged in work
      at the nexus of youth justice-welfare. Whilst often characterized as
      contradictory tendencies, the article demonstrates that a social welfare ethic
      and a criminal justice ethic were coexistent within the rhetoric and practice of
      policing, but that they operated in a state of flux. It also argues that styles
      of policing were subject to change, particularly as the use of discretionary and
      informal methods was increasingly challenged, as physical violence was
      increasingly seen as an outmoded recourse for the institutions of criminal
      justice, and as the policing of youth was increasingly politicized. The post-war
      period can be characterized in terms of greater levels of public scrutiny, the
      formalization of processes previously undertaken through informal or semi-formal
      mechanisms, and attempts (not always successful) to systematize procedures
      nationally in terms of the Scottish state.

PMID- 21879584
TI  - Japan hospitals. Foreword.

PMID- 21879585
TI  - Collaborative work among healthcare professionals and the regeneration of
      hospital care.

PMID- 21879586
TI  - Reaching toward a bright future for the Japan Hospital Association (JHA)-
      healthcare cost reduction policy breakthrough. A local hospital director's
      efforts.

PMID- 21879587
TI  - Medical tourism--why are Japanese hospitals still incapable, resistive or opposed
      to competing in this global trend?

PMID- 21879588
TI  - Crisis of novel infectious diseases: why don't Japan have enough vaccines?

PMID- 21879589
TI  - Effect on self-esteem of workshop to induce laughter through praise.

PMID- 21879590
TI  - Preventive care strategies based on disease prevalence among Japanese urban
      elderly: focus on disease prevention in mildly frail elders with long-term care
      insurance.
AB  - AIM: To investigate the relationship between prevalent diseases and medical
      conditions in frail elderly in Japan who require lighter levels of care in order
      to improve preventive care strategies. METHODS: Data from Japanese long-term care
      insurance (LTCI) documentation was used to investigate the relationship between
      the prevalence of diseases and medical conditions among 553 frail elderly people
      (193 men and 360 women) over 65 years old in a central area of Osaka prefecture.
      Logistic regression analysis was used to determine the associations among related
      diseases and main medical conditions in the lightest levels of care required.
      RESULTS: With age, the prevalence of hypertension, heart disease, dementia, and
      fractures increased, whereas neoplasms, cerebrovascular disease, and diabetes
      mellitus decreased. Neoplasms and circulatory disease were significantly more
      common in men, and musculoskeletal disease and injury were more common in women
      among main medical conditions requiring light care. Diseases significantly
      associated with the lightest level of care were hyperlipidemia (odds ratio 3.0),
      osteoporosis without fracture (1.9), and gonarthrosis (1.7) in women.
      CONCLUSIONS: Efforts to control musculoskeletal diseases and lifestyle diseases
      are essential preventive care strategies, especially in the preliminary stages of
      care under LTCI. Previously proven measures such as the cancer screening,
      intensive blood pressure control, continuous nutritional management, and thorough
      diabetes treatment beginning in middle age can help to prevent fractures, cancer,
      cerebrovascular disease, and dementia, all of which severely erode quality of
      life.

PMID- 21879591
TI  - Main medical conditions of frail elderly patients that require intensive care
      under the Japanese Long-Term Care Insurance (LTCI) system: a comparison with
      German LTCI.
AB  - BACKGROUND: Although the number of frail elderly individuals has rapidly
      increased with global aging, few studies have assessed the main medical
      conditions that are covered by Long-Term Care Insurance (LTCI) systems.
      OBJECTIVES AND METHODS: To improve preventive care strategies, the author
      researched data from 553 frail elderly individuals above 65 years of age in the
      Osaka central area. Logistic regression analysis was used to identify severe
      diseases associated with levels of care higher than level 3 (3+) under the
      Japanese LTCI system, which is equivalent to the care standards of the German
      LTCI system. The main medical conditions were also compared between the LTCI
      systems of both countries. RESULTS: Diseases significantly associated with
      Japanese level of care 3+ were renal failure (odds ratio 6.3), fracture (5.3),
      dementia (4.4), and cerebrovascular disease (CVD; 2.5) in males and fracture
      (7.5), heart failure (3.6), dementia (3.3), CVD (2.9), and depression (2.8) in
      females. Main medical conditions in Japanese patients by gender were dementia
      (males 29%, females 21%), CVD (males 27%, females 22%), neoplasm (males 11%), and
      fracture or fracture sequelae (females 24%). Among German LTCI recipients, the
      main medical conditions by gender were diseases of the circulatory system (males
      23%, females 19%) and mental and behavioral disorders (males 17%, females 20%).
      CONCLUSION: Dementia and diseases of the circulatory system, especially CVD, were
      the most common main recipients. Intensive blood pressure control and thorough
      diabetes treatment are the top preventive healthcare strategies for both diseases
      of the circulatory system and dementia to avoid disease progression and
      accumulation. Early detection and treatment of cancer in males and prevention of
      fractures in females are of particular importance.

PMID- 21879592
TI  - [Trophoblast differentiation and its regulation in pathologic process of
      pregnancy induced hypertension].

PMID- 21879593
TI  - Various skin manifestations of mycosis fungoides: histopathological features and
      prognosis.
AB  - Mycosis fungoides (MF) is a type of T cell lymphoma, and comprises more than one
      half of primary cutaneous T cell lymphomas (CTCL). Many variants of MF have been
      reported to date, although there are only three descriptions of MF variants in
      the WHO-EORTC classification published in 2005. Herein, we present four cases of
      MF, namely classical MF, Woringer-Kolopp disease, bullous MF, and folliculotropic
      MF. These variants of MF were all typical, although they are quite rare. Their
      unique clinical manifestations arise from characteristic histolopathological
      changes in the lesions. The location and amount of infiltrating tumor cells in
      the epidermis seem to be profoundly correlated with the prognosis.

PMID- 21879594
TI  - An autopsy case of misdiagnosis based on postmortem computed tomography findings.
AB  - A middle-aged man was found lying beside his bicycle on an early winter morning.
      The cause of death was diagnosed by clinicians as traumatic intracerebral
      hemorrhage and cerebral contusion with frontal bone fracture based on the
      findings of Computed Tomography (CT) of the head. However, forensic autopsy
      revealed that there were no evidences of intracerebral hemorrhage and left
      frontal bone fracture but the defect of golf ball size on the frontal lobe which
      was considered to be a complication from the old cerebral contusion and old bone
      fracture. The bleeding and pooling blood from subarachnoid hemorrhage (SAH) to
      the frontal lobe defect had the appearance of an intracerebral hemorrhage.
      Disruption of left renal artery was found and the cause of death was diagnosed as
      massive hemorrhage due to this rupture. Although postmortem CT is a useful tool
      for obtaining information on the body prior to conducting an autopsy, it should
      be used with extreme caution.

PMID- 21879595
TI  - [A study of the structure of bioceramic coatings obtained by plasma spraying of
      hydroxyapatites of synthetic and biological origins].

PMID- 21879596
TI  - [A bio-impedance meter providing measurement of the active and reactive
      components].

PMID- 21879597
TI  - [Hardware implementing a parallel association method for recovering associative
      functions of speech in patients with sensory aphasia].

PMID- 21879598
TI  - [A thermopulser with a channel for thermopulsing session efficiency assessment].

PMID- 21879599
TI  - [An autonomous orthopedic rehabilitation device for automated osteosynthesis].

PMID- 21879600
TI  - [A small-size autonomous electrostimulation probe].

PMID- 21879601
TI  - [Approaches to determining the source and assessing the dynamics of spontaneous
      pathological brain activity in patients with chronic pain syndromes based on a
      labView virtual device system].

PMID- 21879602
TI  - Health. Vaccinate or leave. More pediatricians are firing families for not giving
      their kids shots.

PMID- 21879603
TI  - Galen and astrology: a Mesalliance?
AB  - The author examines the question of Galen's affinity with astrology, in view of
      Galen's extended astrological discussion in the De diebus decretoriis (Critical
      Days). The critical passages from Galen are examined, and shown to be superficial
      in understanding. The author performs a lexical sounding of Galen's corpus, using
      key terms with astrological valences drawn from the Critical Days, and assesses
      their absence in Galen's other works. He compares Galen's astrology with the
      astrology of Ptolemy's Tetrabiblos, and evaluates their respective strategies of
      scientific reasoning. Three types of inference are introduced and applied to
      Galen's astrology. Finally, he concludes that the empirical side of Galen's
      science does not depend upon astrological methods or concepts, but that these
      were introduced for their rhetorical effect in presenting his new medical
      methodology. It is suggested that continued attention to Galen's astrology has
      obscured the truly important empirical scientific method that Galen developed.

PMID- 21879604
TI  - Science as an ally of religion: a Muslim appropriation of 'the conflict thesis'.
AB  - John W. Draper's History of the Conflict between Religion and Science (1874) is
      commonly regarded as the manifesto of the 'conflict thesis'. The superficiality
      of this thesis has been demonstrated in recent studies, but to read Draper's work
      only as a text on 'science versus religion' is to miss half of its significance,
      as it also involved evaluations of individual religions with respect to their
      attitudes towards science. Due to Draper's favourable remarks on Islam, the
      Ottoman author Ahmed Midhat translated his work into Turkish, and published it
      along with his own comments on Draper's arguments. Midhat interpreted Islam using
      the cues provided by Draper, and portrayed it as the only religion compatible
      with science. While his Christian readers condemned Draper for his approach to
      Islam, Midhat transformed the 'conflict thesis' into a proclamation that Islam
      and science were allies in opposition to Christian encroachment on the Ottoman
      Empire. This paper analyses Midhat's appropriation of Draper's work and compares
      it to the reaction of Draper's Christian readers. It discusses the context that
      made an alliance between Islam and science so desirable for Midhat, and
      emphasizes the impact of the historico-geographical context on the encounters
      between and representations of science and religion.

PMID- 21879605
TI  - Linnaeans outdoors: the transformative role of studying nature 'on the move' and
      outside.
AB  - Travelling is an activity closely associated with Carolus Linnaeus (1707-1778)
      and his circle of students. This article discusses the transformative role of
      studying nature outdoors (turning novices into naturalists) in eighteenth-century
      Sweden, using the little-known journeys of Carl Back (1760-1776), Sven Anders
      Hedin (1750-1821) and Johan Lindwall (1743-1796) as examples. On these journeys,
      through different parts of Sweden in the 1770s, the outdoors was used,
      simultaneously, as both a classroom and a space for exploration. The article
      argues that this multifunctional use of the landscape (common within the Linnaean
      tradition) encouraged a democratization of the consumption of scientific
      knowledge and also, to some degree, of its production. More generally, the study
      also addresses issues of how and why science and scientists travel by discussing
      how botanical knowledge was reproduced and extended 'on the move', and what got
      senior and junior students moving.

PMID- 21879606
TI  - Johann Wilhelm Hittorf and the material culture of nineteenth-century gas
      discharge research.
AB  - In the second half of the nineteenth century, gas discharge research was
      transformed from a playful and fragmented field into a new branch of physical
      science and technology. From the 1850s onwards, several technical innovations
      powerful high-voltage supplies, the enhancement of glass-blowing skills, or the
      introduction of mercury air-pumps- allowed for a major extension of experimental
      practices and expansion of the phenomenological field. Gas discharge tubes served
      as containers in which resources from various disciplinary contexts could be
      brought together; along with the experimental apparatus built around them the
      tubes developed into increasingly complex interfaces mediating between the human
      senses and the micro-world. The focus of the following paper will be on the
      physicist and chemist Johann Wilhelm Hittorf (1824-1914), his educational
      background and his attempts to understand gaseous conduction as a process of
      interaction between electrical energy and matter. Hittorf started a long-term
      project in gas discharge research in the early 1860s. In his research he tried to
      combine a morphological exploration of gas discharge phenomena-aiming at the
      experimental production of a coherent phenomenological manifold--with the
      definition and precise measurements of physical properties.

PMID- 21879607
TI  - 'Sexual chemistry' before the pill: science, industry and chemical
      contraceptives, 1920-1960.
AB  - The history of contraceptives met the history of drugs long before the invention
      of the contraceptive pill. In the first half of the twentieth century, numerous
      pharmaceutical laboratories, including major ones, manufactured and marketed
      chemical contraceptives: jellies, suppositories, creams, powders and foams
      applied locally to prevent conception. Efforts to put an end to the marginal
      status of these products and to transform them into 'ethical' drugs played an
      important role in the development of standardized laboratory tests of efficacy of
      contraceptive preparations; debates on the validity of such tests; evaluation of
      the long-term toxicity of chemical compounds; and the rise of collaborations
      between activists, non-profit organizations and the pharmaceutical industry.
      Chemical contraceptives were initially associated with quack medicine, shady
      commercial practices and doubtful morality. Striving to change the status of
      contraceptives and to promote safe and efficient products that reduced fertility
      in humans shaped some of the key features of the present-day production and
      regulation of pharmaceuticals.

PMID- 21879608
TI  - Disability, absence and the health reform era.
AB  - The total cost of employee absence for many employers is high, and the
      correlation between employee health and disability is clear. This article reviews
      several challenges employers face in managing employee health and absence in a
      well-integrated manner. Although such an undertaking is not easy, the additional
      cost national health care reform may bring makes the interrelationship between
      employer profitability and employee absence, health and disability more crucial
      than ever for employers to recognize and manage.

PMID- 21879609
TI  - Improving workplace productivity--it isn't just about reducing absence.
AB  - Employers must get more aggressive in their health and productivity strategies. A
      comprehensive strategy includes data analytics across health and lost-time
      programs, absence policies that meet today's needs for both employer and
      employee, health and wellness programs targeting modifiable health behaviors, and
      absence program administration that is aligned to operational goals. This article
      targets key aspects of a comprehensive long-term health and productivity
      strategic vision. An organization can use these aspects independently to address
      immediate tactical issues while it develops its broader strategy. The target
      areas include a view from the perspective of data management, absence program
      design and management, employee health and wellness, and behavioral health.

PMID- 21879610
TI  - The impact of health reform on HSAs.
AB  - The health care reform law contains only two direct changes to health savings
      accounts (HSAs): eliminating the ability to use the HSA for over-the-counter
      drugs and increasing the early withdrawal penalty from 10% to 20%. The indirect
      changes, however, could drastically curtail the growth of HSAs or even result in
      the end of HSAs. The actual impact is uncertain at this time because much of the
      detail of the law is left to regulatory interpretation. This article identifies
      and analyzes seven areas in the new law that could indirectly impact HSAs.

PMID- 21879611
TI  - Legal update. Subrogation--contractual right to reimbursement--Common Fund
      Doctrine disclaimer.
AB  - Zurich Am. Ins. Co. v. O'Hara, 604 F3d 1232, 49 EBC. (BNA) 1018, (11th Cir.
      2010). Court upheld Zurich's right to reimbursement for medical expenses from the
      proceeds of any full or partial recovery given the explicit plan language so
      providing "regardless of whether the covered person has been fully compensated or
      made whole."

PMID- 21879612
TI  - Legal update. Definition of accident--accidental death and dismemberment--alcohol
      related automobile collision--foreseeability of death as result of driving while
      intoxicated.
AB  - LaAsmar v. Phelps Dodge Corp. Life, Accidental Death & Dismemberment & Dependent
      Life Ins. Plan, 605 F3d 789, 2010 WL 1794437(10th Cir. 2010). A death caused by
      an alcohol-related automobile collision qualifies as an "accident" that would
      require payment of accidental death and dismemberment plan benefits.

PMID- 21879613
TI  - Duration discrimination by musicians and nonmusicians.
AB  - This study investigated the effects of stimulus modality, standard duration, sex,
      and laterality in duration discrimination by musicians and nonmusicians.
      Seventeen musicians (M age = 24.1 yr.) and 22 nonmusicians (M age = 26.8 yr.)
      participated. Auditory (1,000 Hz) and tactile (250 Hz) sinusoidal suprathreshold
      stimuli with varying durations were used. The standard durations tested were 0.5
      and 3.0 sec. Participants discriminated comparison stimuli which had durations
      slightly longer and shorter than the standard durations. Difference limens were
      found by the method of limits and converted to Weber fractions based on the
      standard durations. Musicians had lower, i.e., better, Weber fractions than
      nonmusicians in the auditory modality, but there was no significant difference
      between musicians and nonmusicians in the tactile modality. Auditory
      discrimination was better than tactile discrimination. Discrimination improved
      when the standard duration was increased both for musicians and nonmusicians.
      These results support previous findings of superior auditory processing by
      musicians. Significant differences between discrimination in the millisecond and
      second ranges may be due to a deviation from Weber's law and the discontinuity of
      timing in different duration ranges reported in the literature.

PMID- 21879614
TI  - Facial resemblances between heterosexual, gay, and lesbian couples.
AB  - Researchers have noted a physical resemblance (homophily) between human sex
      partners. To date, these studies and their related interpretations have been
      based on heterosexual couples. The present study compared physical resemblances
      between gay, lesbian, and heterosexual couples, using 40 photographs of each from
      national newspapers, which were rated by 34 men and 56 women (M age = 53 yr., SD
      = 12.1). Half the photographs were of actual couples and half were randomly mixed
      within each group. Actual couples were rated as significantly more similar in
      appearance than random pairings of people. Ratings of similarity were
      significantly higher (indicating greater perceived homophily) for gay couples
      than heterosexual couples, while there was no statistically significant
      difference in similarity ratings between lesbian couples versus gay and
      heterosexual couples. The results were interpreted in terms of evolutionary and
      parental imprinting hypotheses.

PMID- 21879615
TI  - Repetition of educational AIDS advertising affects attitudes.
AB  - In educational AIDS campaigns, initiators often use advertisements to warn about
      the threat of AIDS. The present Internet study (N = 283) tested the assumption of
      an inverted U-shaped relationship between the number of educational AIDS
      advertisements in a magazine and the perceived threat of AIDS among different
      groups (i.e., homosexual men and heterosexual men and women). This expectation
      was primarily based on signaling theory, which assumes that recipients use
      repetition frequency as a cue for judgments about the message. Results provided
      support for the expected inverted U-curve.

PMID- 21879616
TI  - Sexual orientation and shifts in preferences for a partner's body attributes in
      short-term versus long-term mating contexts.
AB  - This study assessed the effects of short- and long-term mating contexts on
      preferences for body characteristics of potential relationship partners in
      lesbians and heterosexual women. Lesbians (n = 41) rated figure drawings and
      computer-generated images of women that varied in body fat, waist-to-hip ratio,
      and breast size; heterosexual women (n = 95) rated computer-generated images of
      men that varied in muscularity and body fat. Both lesbians and heterosexual women
      showed a shift in preferences toward more physically attractive partners for
      shortterm relationships. All body aspects were affected, except that heterosexual
      women did not show a preference shift for male body fat. The results were
      interpreted in terms of a mating trade-off strategy in which mate preferences are
      the consequence of cost/benefit analyses and suggest that preferences for
      physical attributes of sexual partners may be shared by members of the same sex
      regardless of sexual orientation.

PMID- 21879617
TI  - Willingness to date across race: differences among gay and heterosexual men and
      women.
AB  - Willingness to date members of other races was examined among 200 men with same
      sex dating preference (n = 100) and opposite-sex dating preference (n = 100), and
      200 women with same-sex dating preference (n = 100) and opposite-sex dating
      preference (n = 100) who were randomly selected from an Internet dating web site.
      Overall, results indicated a greater willingness among gay participants than
      heterosexual participants to date people of other races. A 2 (Sex) x 2 (Sexual
      Orientation) analysis of variance showed an interaction, with lesbian women more
      willing to date other races than gay men, while among heterosexual participants
      men were more willing than women to date other races. The role of mate selection
      theory, and the importance of the status afforded various races in U.S. society,
      were applied to interpret people's willingness to date other races.

PMID- 21879618
TI  - Leadership and satisfaction in change commitment.
AB  - Managerial transformational leadership skills may directly influence banking
      counter staff toward change commitment and improve job satisfaction and service
      quality, or the influence instead may be mediated by change commitment. For a
      sample comprised of 246 managers from four large Taiwanese banks, the following
      path relationships were tested: (1) the association of transformational
      leadership with change commitment, (2) the association of change commitment with
      job satisfaction, and (3) the direct or indirect (through the mediation of change
      commitment) effect of transformational leadership on job satisfaction. Regression
      was utilized to gain insight into the effects of transformational leadership and
      change commitment on job satisfaction. Transformational leadership may foster
      change by providing psychological support to the banking counter staff, enabling
      them to use their skills to meet the needs of individual customers in response to
      complex environments.

PMID- 21879619
TI  - Love styles, shyness, and patterns of emotional self-disclosure.
AB  - Previous research has shown a relationship between love styles and shyness. This
      study explored the possibility that this effect may be due to differences in
      patterns of self-disclosure associated with shyness. University student
      participants (N = 143) completed the Love Attitudes Scale, the Emotional Self
      Disclosure Scale, and the Revised Cheek and Buss Shyness Scale. Correlations
      between the measures were calculated and significant results ranged from r = .18
      to .30. Findings supported previous research in showing significant relationships
      between shyness and love styles; self-disclosure showed no relationship with
      shyness but did show some direct associations with love style scores. Results are
      discussed in relation to the importance of self-disclosure in relationship
      development.

PMID- 21879620
TI  - Development of a measure of work motivation for a meta-theory of motivation.
AB  - This study presents a measure of work motivation designed to assess the
      motivational concepts of the meta-theory of motivation. These concepts include
      intrinsic process motivation, goal internalization motivation, instrumental
      motivation, external self-concept motivation, and internal self-concept
      motivation. Following a process of statement development and identification, six
      statements for each concept were presented to a sample of working professionals
      (N = 330) via a paper-and-pencil questionnaire. Parallel analysis supported a 5
      factor solution, with a varimax rotation identifying 5 factors accounting for
      48.9% of total variance. All 5 scales had Cronbach alpha coefficients above .70.
      Limitations of the newly proposed questionnaire and suggestions for its further
      development and use are discussed.

PMID- 21879621
TI  - Reliability and validity of a bilingual measure of religiosity in English and
      Vietnamese: preliminary results from a pilot study.
AB  - This study reports preliminary psychometric findings for a seven-item religiosity
      scale in a community-based sample of Vietnamese Americans ages 18 to 83 years (N
      = 119; 58% women, 42% men). A bilingual survey was distributed to Vietnamese who
      were evacuated during Hurricane Katrina and had returned after the disaster.
      Internal consistency, factorial structure validity, and criterion validity were
      evaluated on the scale items. The bilingual scale had good internal consistency.
      While exploratory and confirmatory factor analysis results provided support for a
      two-factor structure which captured Religious Involvement and Religious Coping, a
      one-factor model had slightly better fit. Individuals who scored high on the
      religiosity scale reported a significantly lower score on their stressful
      experiences during the hurricane, providing evidence of criterion validity.

PMID- 21879622
TI  - Subjectivity and environmental influence in relation to sense of authenticity.
AB  - The authors responded to criticisms raised recently by Giannini (2010) of the
      authors' 2009 study in which cross-age differences were examined in the sense of
      authenticity. Comments address three aspects of the criticism, interpretation of
      the results, and misunderstanding of the method used as well as the concepts. In
      particular, future research likely needs to focus on the subjective aspects of
      sense of authenticity.

PMID- 21879623
TI  - Measuring intention in language learning: a confirmatory factor analysis.
AB  - Intention in language learning has not been studied effectively in research on
      second language (L2) learning. The goal is to fill this gap by designing and
      testing a measure of L2 learning intention. The scale was differentiated into two
      distinct but correlated components, goal intention and implementation intention,
      within the L2 context. The two intention scales were examined for reliability and
      validity using a series of standard psychometric procedures. A confirmatory
      factor model was then constructed and tested with a sample of 333 senior high
      school and college students. The results showed that a modified model had good
      psychometric characteristics and reasonable fit to the data.

PMID- 21879624
TI  - Taiwanese members' report of verbal interactions and their relations to
      demographic variables in the group counseling process.
AB  - The purpose was to examine differences in verbal interactions during the group
      counseling process and the relationship between perceived verbal interactions and
      members' demographic variables. 42 participants were recruited and randomly
      assigned to one of four counseling groups. Based on the Hill Interaction Matrix,
      Quadrant 4 verbal interactions, consisting of Speculative and Confrontative
      verbal behaviors in Personal and Relationship levels, were perceived
      significantly more often at the closing stage than at the initial stage.
      Furthermore, the perceived verbal interactions were related to the demographic
      variables of sex, educational level, and group experience, but not
      acquaintanceship. The findings suggested that the higher ratings of perceived
      Speculative and Confrontative verbal behaviors and the lower ratings of Assertive
      and Silence verbal interactions must be interpreted cautiously from a cross
      cultural perspective, especially in Asian cultures.

PMID- 21879625
TI  - The social adjustment, academic performance, and creativity of Taiwanese children
      with Tourette's syndrome.
AB  - The purpose was to describe the social adjustment, academic achievement, and
      creativity of 127 Taiwanese children with Tourette's Syndrome and a control group
      of 138 Taiwanese children with typical development and reports of the parents of
      both groups. The Tourette's Syndrome group had significantly more disruptive
      behaviors than the controls; most parents reported their children with Tourette's
      Syndrome had high academic achievement although the children scored significantly
      lower than controls on the Elaboration subtest of Creative Thinking.

PMID- 21879626
TI  - Managing antidepressants in primary care: physicians' treatment modifications.
AB  - To examine antidepressant management practices in primary care, patients (N =
      148) given an antidepressant for at least one month completed the Beck Depression
      Inventory (BDI-II), the Patient Health Questionnaire-9 (PHQ-9), and a demographic
      survey. Participants' mean age was 50.7 yr. and 80% were women. Patients' charts
      indicated whether physicians had made changes to prescribed antidepressants or
      dose either 6 wk. before or 6 wk. after study entry. For the 87% of participants
      whose depression status could be determined, 10% met dysthymic disorder criteria
      and only 33% had had a medication change in the previous month. Major depressive
      disorder occurred in 37% but only 18% had had a medication change. Co-existing
      dysthymic disorder and major depressive disorder were diagnosed in 34%, with 24%
      receiving a medication change. Participants not receiving a medication change had
      mean BDI-II scores indicating moderate depression. Lack of antidepressant
      adjustment suggests physicians may need to monitor depressive symptoms closely
      using protocols and prompts.

PMID- 21879627
TI  - Depression symptoms among Omani children: age and sex differences.
AB  - The present study explored the existence of depressive symptoms among Omani
      children according to sex and age. The Arabic translated version of the
      Multidimensional Child and Adolescent Depression Scale was administered to 1,749
      children (828 boys, 921 girls) ranging in age from 10 to 18 years old (M= 13.9,
      SD = 2.3) from 10 schools representing different areas of Muscat, Oman. The
      results showed no differences in the total mean scores on depression between boys
      and girls, although differences were observed on 4 of the 8 subscales. Boys had
      significantly higher scores on Weak concentration and Loneliness, while girls
      scored higher for Sleep problems and Anhedonia. Significant differences across
      ages also were exhibited for the total score as well as four subscales
      (Pessimism, Weak concentration, Anhedonia, and Fatigue), suggesting higher rates
      of depression among 15- to 18-year-olds.

PMID- 21879628
TI  - MBTI and historical data.
AB  - The Myers-Briggs Type Indicator presents a model of personality which may be
      useful for understanding historical personalities, but empirical verification is
      necessary.

PMID- 21879629
TI  - Screening for attention-deficit/hyperactivity disorder in adult inpatients with
      psychiatric disorders.
AB  - The purpose was to assess the effectiveness of the adult ADHD Module from the
      MINI International Neuropsychiatric Interview (MINI) and the Conners' Adult ADHD
      Rating Scales: Screening Version DSM-IV ADHD Symptoms Total Scale (CAARS-S:SV) in
      screening for attention-deficit/hyperactivity (ADHD) disorder in patients
      hospitalized for other psychiatric disorders. Assessment measures were
      administered to 55 (50%) female and 55 (50%) male adult (>18 yr. old) inpatients.
      Only six (5%) of the 110 inpatients had been diagnosed with comorbid ADHD
      according to medical charts. In contrast, 55 (50%) patients met criteria for ADHD
      according to the MINI, and 39 (36%) patients met criteria on the CAARS-S:SV. The
      higher rates of prevalence for the MINI and the CAARS-S:SV were attributable to
      symptom criteria for ADHD being similar to those shared with comorbid disorders.

PMID- 21879630
TI  - Distractors interfere with numerical estimation in Chinese college students as a
      function of field-dependent or field-independent cognitive style.
AB  - Field-dependent/independent groups' numerical estimation was assessed with
      respect to different distractors. Participants were 81 college students with
      field-dependent or field-independent cognitive styles. Cognitive style had a
      significant main effect on reaction without distractors. When the number of
      distractors was double the number of targets, the estimation accuracy of the
      field-dependent and field-independent groups differed. Under this double
      distractors condition, both the field-dependent and field-independent
      participants used logarithmic representation more than linear representation in
      their numerical estimations, but no significant between-group differences were
      found.

PMID- 21879631
TI  - Explaining inconsistencies in Shakespeare's character Henry V on the basis of the
      emotional undertones of his speeches.
AB  - Shakespeare's character Henry V is infamous, among 20th-century analysts of
      drama, for his inconsistent disposition. Some analysts highlight this character's
      reformation and others his Machiavellian tendency to moderate his disposition in
      tune with changing situations. The Dictionary of Affect in Language (Whissell,
      2009) was used to score the emotional undertones of words in Henry V's dialogue.
      Analyses of these undertones, described in terms of Pleasantness and Activation,
      demonstrated that the character Henry V was, in overall terms, emotionally
      average, that there was minimal evidence of growth or reform in him across time,
      and that situational factors (e.g., revelry, kingship, courtship, battle) were
      associated with the dramatic changes in his speeches. The character employed more
      passive language in private and personal situations and more active language in
      his (public) royal role. Four categories of Henry V's speeches (Condescension,
      Control, Self-definition, and the Courtship of Good Opinion), represented in both
      public and private discourse, reflected increasing pleasantness in emotional
      undertones.

PMID- 21879632
TI  - Measuring childhood abuse and neglect in a group of female indoor sex workers in
      the Netherlands: a confirmatory factor analysis of the Dutch version of the
      Childhood Trauma Questionnaire-Short Form.
AB  - Confirmatory factor analysis was performed on the responses to the Dutch version
      of the Childhood Trauma Questionnaire-Short Form from a sample of 123 female
      indoor sex workers in The Netherlands. Results indicate the expected five-factor
      structure fit the data well. In line with Bernstein and others, the instrument
      was a valid measure of retrospective childhood abuse and neglect in this sample.

PMID- 21879633
TI  - Influencing factors on color and product-function association.
AB  - The associations of age, sex, and matching types with color and product-function
      were examined in a real-world product scenario (shampoo) among 128 volunteers (M
      age = 29.3 yr.; SD = 15.6). A pilot study identified eight popular colors and
      eight product-functions. The association between color and product-function was
      explored in the main sample. Responses suggested seven pairings of color/product
      functions: Red/Hot oil treatment, Yellow/Bright and shiny hair, Green/Herbal
      extracts, Blue/Deep cleaning, Purple/Soothing, Black/Antiseptic, and White/Anti
      dandruff. Analyses indicated that adult participants required more repetitions
      for retention, as did memorization with random pairing compared to participant
      selected pairings. There were statistically significant correlations of responses
      to colors and product functions. With known color/product-function associations,
      manufacturers might promote their products more effectively. It is suggested that
      the associations might be sex- or culture-specific.

PMID- 21879634
TI  - Self-reported inability to cry as a symptom of anhedonic depression in
      outpatients with a major depressive disorder.
AB  - To ascertain whether self-reported inability to cry would be associated with
      symptoms of anhedonic depression, the 21-item Beck Depression Inventory-II was
      administered to 1,050 outpatients diagnosed with a DSM-IV-TR major depressive
      disorder. 219 (21%) patients reported on the BDI-II Crying item that they were
      unable to cry, and 831 (79%) patients reported they were able to cry. Only BDI-II
      Loss of Interest was significantly associated with the inability to cry after the
      other BDI-II symptoms were controlled for using a multiple logistic-regression
      analysis. The inability to cry was discussed as an indicator of anhedonic
      depression.

PMID- 21879635
TI  - Psychosocial profile of people with AIDS and their caregivers in Egypt.
AB  - Caring for individuals with AIDS in developing countries represents a major
      crisis to families and natural caregivers. This study presents the psychosocial
      profiles of people with AIDS and their caregivers in Egypt to assess the effects
      of HIV/AIDS on patients, their caregivers, and the factors that influence
      caregiving and support. Various stressors and challenges for patients as well as
      hardships the caregiver faces were explored. The literature documents
      difficulties such as inadequate health care services, lack of resources, and
      stigma that patients experience in developing countries. Findings indicate an
      association between the psychosocial effects of AIDS on patients and their
      caregivers.

PMID- 21879636
TI  - Spatial and nonspatial working memory and visual search.
AB  - It has been indicated that visual search is interfered with in spatial working
      memory (WM), although not in nonspatial WM. In this study, the effects on visual
      search of individual differences in spatial and nonspatial WM were examined. Two
      visual search conditions were used: a conjunction search condition comprising two
      features (color and shape) and a disjunction condition comprising only one
      feature (color or shape). 96 participants (42 men, 54 women, M age = 20.9 yr., SD
      = 3.5) participated in this study. The participants were divided into high and
      low WM groups based on their spatial and nonspatial WM test scores. As a result,
      statistically significant group differences in the conjunction search rate were
      observed in spatial WM but not in nonspatial WM. These results suggest there is a
      relationship between visual search and the individual spatial WM ability, but
      this does not hold for nonspatial WM.

PMID- 21879637
TI  - Characteristics of juvenile offenders with invalid and valid MMPI--a profiles.
AB  - The issue of what type of juvenile offender produces an invalid versus a valid
      Minnesota Multiphasic Personality Inventory, Adolescent Form (MMPI-A) profile
      requires study. Using technical manual profile invalidation requirements from a
      cohort sample of 1,054 juvenile offenders, 387 produced invalid profiles, whereas
      667 yielded valid profiles. Utilizing scale scores from the Millon Adolescent
      Clinical Inventory (MACI), univariate and multivariate analyses for girls, boys,
      and combined samples of invalid and valid MMPI-A profiles suggested similarities
      and differences which influenced the results for the combined samples. The groups
      were separated on the following MACI scales: Disclosure, Impulsivity, Substance
      Abuse Propensity, Unruly, and Oppositional by sex and for the combined group.
      Also noted were other MACI scales which distinguished boys and girls in
      comparisons made between as well as within the invalid and valid profiles.

PMID- 21879638
TI  - Stress, hope, and loneliness in young adolescents.
AB  - A sample of 134 young adolescents attending a middle school responded to the
      Perceived Stress Scale, the Hopefulness Scale for Adolescents, and the Revised
      UCLA Loneliness Scale. Correlational analyses indicated that higher scores on
      stress were significantly associated with lower scores on hope (r = -.55) and
      higher scores on loneliness (r = .52). Unlike an earlier study with predominately
      ethnic minority adolescents, the present findings with predominately Euro
      American adolescents supported the relationship proposed between stress and hope;
      the relationship proposed between stress and loneliness was supported.

PMID- 21879639
TI  - Evaluation of a psychosocial intervention on social support, perceived control,
      coping strategies, emotional distress, and quality of life of breast cancer
      patients.
AB  - The purpose of this research was to demonstrate that a specific psychosocial
      intervention changes reactions to cancer and quality of life. This study was
      carried out on 66 patients with a first breast cancer. Patients were randomly
      divided into two groups: a specific intervention group (G1, 8 sessions) or a
      support group (G2, 8 sessions). A control group (G3) was composed of patients who
      refused to participate in psychological intervention. Social support, perceived
      control, repression of emotions, coping strategies, emotional distress, and
      quality of life were assessed one week before (T1) and at the end (T2) of the
      psychological intervention. Results showed that G1 did not have significantly
      modified quality of life or psychological scores. Patients of G2 had poorer
      emotional quality of life, use of internal causal attributions, and minimized
      their illness at T1 as compared to patients of G3. At Time 2 these differences
      were not observed.

PMID- 21879640
TI  - When causality does not imply correlation: more spadework at the foundations of
      scientific psychology.
AB  - Experimental research in psychology is based on an open-loop causal model which
      assumes that sensory input causes behavioral output. This model was tested in a
      tracking experiment where participants were asked to control a cursor, keeping it
      aligned with a target by moving a mouse to compensate for disturbances of
      differing difficulty. Since cursor movements (inputs) are the only observable
      cause of mouse movements (outputs), the open-loop model predicts that there will
      be a correlation between input and output that increases as tracking performance
      improves. In fact, the correlation between sensory input and motor output is very
      low regardless of the quality of tracking performance; causality, in terms of the
      effect of input on output, does not seem to imply correlation in this situation.
      This surprising result can be explained by a closed-loop model which assumes that
      input is causing output while output is causing input.

PMID- 21879641
TI  - Comparison of group and individual cognitive-behavioral therapy in reducing fear
      of negative evaluation.
AB  - Previous studies have established the efficacy of group and individual formats of
      cognitive-behavioral therapy in reducing fear of negative evaluation in social
      anxiety disorder, but the effectiveness of the group and individual therapies has
      not been widely assessed. This study was conducted to compare the effectiveness
      of cognitive-behavior group therapy to individual cognitive-behavioral therapy in
      social anxiety disorder. 28 patients were randomly allocated to two groups of 14.
      Each group participated in 12 weekly sessions. The final sample was 22
      participants after drop-out. Pretest and posttest data were collected using the
      Brief Fear of Negative Evaluation Scale and the Beck Depression Inventory-II.
      Controlling for pretest fear of negative evaluation and depression, cognitive
      behavioral group therapy was more effective than individual cognitive-behavioral
      therapy in reducing fear of negative evaluation, but the clinical significance
      and improvement rates of the two treatment formats were equivalent.

PMID- 21879642
TI  - Cross-industry dimensionality of the commitment to change scale in China.
AB  - Commitment to organizational change can explain a range of employees' attitudes
      and behaviors during organizational change, and its measurement is central to
      explaining such organizational linkages. The purpose of this study is to re
      examine the dimensionality of Herscovitch and Meyer's Commitment to Change Scale
      across two different industrial samples in a non-Western cultural context
      (China). The two samples were 198 civil servants (60.0% men; M age = 29.3 yr., M
      organizational tenure = 62.7 mo.) and 442 high-tech company employees (58.2% men;
      M age = 30.5 yr., M organizational tenure = 66.5 mo.) who had respectively
      undergone major changes in compensation and performance appraisal systems in
      their organizations at the time of the research. Results of exploratory and
      confirmatory factor analyses showed that a four-factor model with 14 items fit
      the data best in both samples. The generality of the scale's structure as well as
      its implications for change-management practices are discussed.

PMID- 21879643
TI  - An evolutionary hypothesis of suicide: why it could be biologically adaptive and
      is so prevalent in certain occupations.
AB  - From an evolutionary perspective, suicide is a puzzle, because it has serious
      adverse effects, yet is remarkably common and heritable. An hypothesis is
      proposed to explain this puzzle, by explaining how suicide could be adaptive
      through reducing risk that individuals will transmit infections to kin. Empirical
      evidence supports four predictions from the hypothesis. There are well
      established mechanisms by which infections and immune factors increase risk for
      mental disorders that contribute to suicide. Suicide is more prevalent in
      occupations with greater exposure to infection and immune-compromising factors
      and at higher latitudes, where key environmental factors increase vulnerability
      to infection. In several other highly social species, suicide-like behaviors have
      evolved to reduce transmission of infections. If the hypothesis is correct,
      detection and treatment of underlying infections and immune dysfunction should
      help predict and prevent suicidal behavior, while also combating spread of
      infectious diseases.

PMID- 21879644
TI  - Electroencephalographic responses to photographs: a case study of three women
      with distinct adult attachment interview classifications.
AB  - This preliminary study explored whether neurophysiological responses to visual
      stimuli, including attachment-related pictures, differed based on attachment
      status. Along with self-reported valence ratings and reaction times, recorded
      electroencephalographic (EEG) responses to a total of 100 images, 25 each of
      Positive, Negative, Neutral, and Personal (each participant's parents and child),
      were analyzed within and among three mothers with three attachment statuses
      (Dismissing, Preoccupied, and Secure), as judged by the Adult Attachment
      Interview (AAI). All three mothers gave their highest pleasantness ratings for
      Personal photographs. However, differences emerged when cross-region Alpha2
      activation patterns in response to each picture type were compared amongst
      attachment categories. Alpha2 activation recorded during viewing of the
      participants' children's photographs was similar to viewing Negative pictures for
      mothers with insecure (Dismissing and Preoccupied) status; whereas the Alpha2
      activation of the mother with Secure status towards photographs of her child was
      similar to Positive pictures. Different patterns of hemispheric asymmetry in
      Beta1 frequency when processing different picture types were also found. The
      mother with Dismissing status showed significantly stronger left-hemisphere Beta1
      activation across all image types. The Preoccupied mother showed significantly
      stronger right-hemisphere Beta1 activation for all but the Neutral images, during
      which activation did not differ between the two hemispheres. The mother with
      Secure status showed significantly stronger Beta1 activation in the left
      hemisphere for all but parental Personal photos, during which activation did not
      differ between the two hemispheres. Implications from the current findings and
      future research possibilities are discussed.

PMID- 21879645
TI  - Preoperative cardiac risk management.
AB  - Approximately 100 million people undergo noncardiac surgery annually worldwide.
      It is estimated that around 3% of patients undergoing noncardiac surgery
      experience a major adverse cardiac event. Although cardiac events, like
      myocardial infarction, are major cause of perioperative morbidity or mortality,
      its true incidence is difficult to assess. The risk of perioperative cardiac
      complications depends mainly on two conditions: (1) identified risk factors, and
      (2) the type of the surgical procedure. On that basis, different scoring systems
      have been developed in order to accurately assess the perioperative cardiac risk
      and to improve the patient management. Importantly, patients with estimated high
      risk should be tested preoperatively by non-invasive cardiac imaging modalities.
      According to test results, they can proceed directly to planed surgery with the
      use of cardioprotective drugs (beta-blockers, statins, aspirin), or to myocardial
      revascularization prior to non-cardiac surgery. In this review, we discuss the
      role of clinical cardiac risk factors, laboratory measurements, additional non
      invasive cardiac testing, and consequent strategies in perioperative management
      of patients undergoing noncardiac surgery.

PMID- 21879646
TI  - Preoperative preparation of patients with arterial or pulmonary hypertension in
      noncardiac surgery.
AB  - Arterial hypertension is not an independent risk factor in cardiovascular
      complications in noncardiac surgery. Nevertheless, preoperative evaluation is
      necessary and includes estimation of arterial hypertension grade and possible
      damage of target organs. In patients with first and second grade of arterial
      hypertension postponement of elective intervention is not necessary, only
      optimization of therapy. On the other hand, patients with third level arterial
      hypertension have benefit if intervention is postponed till the reduction of
      arterial pressure. There is no indication that any of the antihypertensive drug
      groups has advantage in the preoperative treatment of hypertension. Unlike
      arterial hypertension pulmonary hypertension increases the risk of cardiac
      morbidity and mortality in the perioperative period. In patients with pulmonary
      hypertension, anesthesia and surgery may be complicated with heart failure,
      hypoxia and arrhythmias. Preoperative and postoperative treatments include
      calcium channel blockers, prostanoids, endothelin receptor antagonists and
      inhibitors of phosphodiesterase type 5.

PMID- 21879647
TI  - Approach to patients with implanted pacemaker and scheduled surgical or
      diagnostic procedure.
AB  - Application of cardiac electrostimulation in strictly defined indications has
      been on the increase over the last few decades. Frequent use of this therapy as
      well as the fact that it is applied predominantly in patients in the seventh
      decade of life, implies possible signifficant comorbidities and need for various
      diagnostic and surgical procedures. These are the reasons we decided to point out
      certain specific features in approaching this patient group in preparation and
      implementation of these procedures. Preoperative approach starts with usual
      patient history, with additional information on the type of pacemaker, last
      pacemaker check and electrocardiogram. This general approach is not substantialy
      different for pacemaker or ICD patients. What is specific is the possible
      interferrence caused by devices used in diagnostic or therapeutic procedures
      (diathermy, lithotripsy). Complications that may arise are usually related to the
      underlying disease rather than the pacemaker malfunction, but still, careful
      approach and pacemaker check are warranted, especially in the group marked as
      "pacemaker dependent". Adequate preoperative assessment, only slightly different
      from the usual, represents a sufficient guarantee for safe procedures diagnostic,
      therapeutic or surgical.

PMID- 21879648
TI  - The preoperative assessment of patients with valvular heart disease as a
      comorbidity.
AB  - In patients with valvular heart disease planned for any type of surgery
      preoperative evaluation and preparation are especially important for a
      successfull outcome of the surgery. Preoperative preparation and intraoperative
      treatment of patients with valvular heart disease are different de-Spending on
      the type of valvular disease: aortic stenosis, aortic regurgitation, mitral
      stenosis, mitral regurgitation or mitral valve prolapse. In this paper we have
      outlined the criteria for evaluating the severity of valvular disease, given that
      the risk in surgery is proportional to the degree of valvular disease. Also,
      given that the risk in surgery is also directly proportional to the type and
      extent of non cardiac surgery, it will be presented recommendations for
      intraoperative monitoring, with the purpose of evaluating patient's hemodynamic
      state, as well as recommendations for perioperative treatment of hypotension,
      tachycardia, and other hemodynamic disturbances. In the paper we will separately
      discuss bacterial endocarditis profilaxys which can occur after the surgery of
      patients with valvular disease. Since the patients with valvular disease, and
      especially the ones with implanted prosthetic valve or heart arrhythmia, are
      usually on oral anticoagulation therapy, it will be given recommendations for
      treatment of patients on oral anticoagulation therapy as part of preoperative
      preparations.

PMID- 21879649
TI  - Preoperative preparation of patients with cardiomyopathies in non-cardiac
      surgery.
AB  - Cardiomyopathies are myocardial diseases in which there is structural and
      functional disorder of the heart muscle, in the absence of coronary artery
      disease, hypertension, valvular disease and congenital heart disease.
      Cardiomyopathies are grouped into specific morphological and functional
      phenotypes: dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive
      cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy and unclassified
      cardiomyopathies. Patients with dilated and hypertrophic cardiomypathy are prone
      to the development of congestive heart failure in the perioperative period. Also,
      patients with hypertrophic and arrhythmogenic right ventricular cardiomyopathy
      are prone to arrhythmias in the perioperative period. Preoperative evaluation
      includes history, physical examination, ECG, chest radiography, complete blood
      count, electrolytes, creatinine, glomerular filtration rate, glucose, liver
      enzymes, urin analysis, BNP and echocardiographic evaluation of left ventricular
      function. Drug therapy should be optimized and continued preoperatively. Surgery
      should be delayed (unless urgent) in patients with decompensated or untreated
      cardiomyopathy. Preoperative evaluation requires integrated multidisciplinary
      approach of anesthesiologists, cardiologist and surgeons.

PMID- 21879650
TI  - Preoperative and perioperative management of patients with pericardial diseases.
AB  - Hemodynamic instability is the major concern in surgical patients with
      pericardial diseases, since general anesthesia and positive pressure ventilation
      may precipitate cardiac tamponade. In advanced constriction diastolic impairment
      and myocardial fibrosis/atrophy may cause low cardiac output during and after
      surgery. Elective surgery should be postponed in unstable patients with
      pericardial comorbidities. Pericardial effusion should be drained percutaneously
      (in local anesthesia) and pericardiectomy performed for constrictive pericarditis
      before any major surgical procedure. In emergencies, volume expansion,
      catecholamines, and anesthetics keeping cardiac output and systemic resistance
      should be applied. Etiology of pericardial diseases is an important issue is the
      preoperative management. Patients with neoplastic pericardial involvement have
      generally poor prognosis and any elective surgical procedure should be avoided.
      For patients with acute viral or bacterial infection or exacerbated metabolic,
      uremic, or autoimmune diseases causing significant pericardial effusion, surgery
      should be postponed until the causative disorder is stabilized and signs of
      pericarditis have resolved.

PMID- 21879651
TI  - Preoperative preparation of vascular patients undergoing nonvascular surgery.
AB  - Patients with vascular diseases mainly caused by atherosclerosis, that are
      undergoing nonvascular surgery, often have co-existing conditions which affect
      their cardiovascular system. Cardiovascular complications are among the most
      common perioperative complications including respiratory complications and
      infections. These include coronary disease, hypertension, heart insufficiency,
      pulmonary hypertension, and renovascular hypertension, among others. Preoperative
      preparation must include the use of beta-blocker therapy, antihypertensive,
      antithrombotic and antilipogenic therapy. Electrocardiogram (ECG) and trans
      thoracic echocardiography are the minimum preoperative diagnostic evaluations
      that should be performed, because complications may arise even in patients
      without prior cardiovascular symptomatology. Venous diseases are the most common
      contemporary diseases affecting people of all age groups and races. Invasive
      diagnostic-therapeutic procedures may cause lesions of venous endothelium, hence
      perioperative prevention of deep vein thrombosis (DVT) with the use of heparin or
      low-molecular -weight heparin (LMWH) should be undertaken.

PMID- 21879652
TI  - Preoperative preparation of patients with infectious and restrictive respiratory
      diseases as comorbidities.
AB  - In patients with respiratory pathology changes in respiratory physiology may lead
      to clinical problems during the conduct of anesthesia and the perioperative
      period. An understanding of the disease processes that can affect the lungs and
      pleura allows the anesthesiologist to account for the potential complications of
      these conditions and manage the anesthetic accordingly. This article describes
      the initial evaluation of a patient with respiratory problems. A thorough medical
      history, physical examination and some functional tests are the keys in decision
      making in preparation for anesthesia and surgery. The burden of respiratory
      disease is reviewed, and some important areas of current interest are
      highlighted.

PMID- 21879653
TI  - Preoperative considerations for patients with chronic obstructive pulmonary
      disease.
AB  - Chronic obstructive pulmonary disease is a risk factor for development of
      intraoperative and postoperative pulmonary complications. Regarding the type and
      the extent of surgical procedure, patients with COPD are at risk of aggravation
      of pulmonary function which leads to complicated perioperative course. In order
      to reduce perioperative complications, preoperative evaluation and preoperative
      patient preparation are of great importance. Goals of preoperative preparation
      and anesthesia in patients with COPD are maintaining ventilation-perfusion ratio,
      preventing development of hipoxemia, intraoperative brochospasm, pneumothorax and
      disturbances of cardivascular system.

PMID- 21879654
TI  - Preoperative preparation of the patient with the abnormalities of red and white
      blood cells.
AB  - The complete peripheral blood count analysis including laboratory screening tests
      of haemostasis and coagulation should be done in every patient before surgery, in
      order to detect specific abnormalities for primary or secundary haematologic
      disorder. These abnormalities might be very important course of perioperative and
      postoperative complications. Anaemia is the most frequent haematologic
      abnormality seen during preoperative period. Therapy approach depends on the type
      and anaemia degree, and also on the type and time of surgery. If surgery is not
      urgent specific therapy according to the anaemia type (iron therapy, vitamin B12,
      folic acid, corticosteroids, recombinant erythropoietin) should be given in all
      anaemias with deficiency of iron, megaloblastic anaemias, acquired haemolytic
      anaemias and anaemias in end stage renal disease. Transfusion of red cells are
      most frequently given in patients with normovolemic anaemias with haemoglobin
      level of 10.0 g/dl and hematocrit of 0.30, but lower levels in haemodynamic
      stable patients. Venesections should be done in patients with erythrocytosis in
      order to reduce total red cell volume, but taking into account the perioperative
      bleeding. Patients with leukocyte abnormalities suspected on primary haematologic
      disorder need urgent haematologic diagnostic procedures. In patients with
      leucocytosis the actual level of neutropenia is the bigger problem than the level
      of leucocytosis. In those patients treatment generally involves preventing
      infections, managing of febrile neutropenia with broad spectrum antibiotics and
      antifungal drugs, treatment with recombinant granulocyte hematopoetic factor,
      rarely transfusions of granulocyte concentrates and intravenous immunoglobulins.

PMID- 21879655
TI  - Preoperative assessment and preparation of patients with diseases affecting the
      central nervous system.
AB  - PURPOSE OF REVIEW: This review will examine the most important issues of
      preoperative evaluation and preparation in relation to patients with deseases
      affecting the central nervous system. Those patients may undergo various forms of
      surgery unrelated to the central nervous system disease. We discuss the effect of
      physiologic and pharmacological factors on cerebral autoregulation and control of
      intracranial pressure alongside its clinical relevance with the help of new
      evidence. RECENT FINDINGS: Regardless of the reason for surgery, coexisting
      diseases of brain often have important implications when selecting anesthetic
      drugs, procedures and monitoring techniques. Suppression of cerebral metabolic
      rate is not the sole mechanism for the neuroprotective effect of anaesthetic
      agents. There are certain general principles, but also some specific
      circumstances, when we are talking about optimal anesthetic procedure for a
      patient with coexisting brain disease. Intravenous anesthesia, such as
      combination of propofol and remifentanil, provides best preservation of
      autoregulation. Among inhaled agents isoflurane and sevoflurane appear to
      preserve autoregulation at all doses, whereas with other agents autoregulation is
      impaired in a dose-related manner. During maintenance of anesthesia the patient
      is ventilated by intermittent positive pressure ventilation, at intermediate
      hyperventilation (PaCO2 25-30 mmHg). SUMMARY: Intraoperative cerebral
      autoregulation monitoring is an important consideration for the patients with
      coexisting neurological disease. Transcranial Doppler based static autoregulation
      measurements appears to be the most robust bedside method for this purpose.

PMID- 21879656
TI  - Preoperative preparation of patients with pituitary gland disorders.
AB  - This paper presents the most common disorders of pituitary function: acromegaly,
      hypopituitarism, diabetes insipidus and syndrome similar to diabetes insipidus,
      in terms of their importance in preoperative preparation of patients. Pituitary
      function manages almost the entire endocrine system using the negative feedback
      mechanism that is impaired by these diseases. The cause of acromegaly is a
      pituitary adenoma, which produces growth hormone in adults. Primary therapy of
      acromegaly is surgical, with or without associated radiotherapy. If a patient
      with acromegaly as comorbidity prepares for non-elective neurosurgical operation,
      then it requires consultation with brain surgeons for possible delays of that
      operation and primary surgical treatment of pituitary gland. If operative
      treatment of pituitary gland is carried out, the preoperative preparation (for
      other surgical interventions) should consider the need for perioperative
      glucocorticoid supplementation. Panhypopituitarism consequences are different in
      children and adults and the first step in diagnosis is to assess the function of
      target organs. Change of electrolytes and water occurs in the case of pituitary
      lesions in the form of central or nephrogenic diabetes insipidus as a syndrome of
      inappropriate secretion of antidiuretic hormone (SIADH). Preoperative preparation
      of patients with pituitary dysfunction should be multidisciplinary, whether it is
      a neurosurgical or some other surgical intervention. The aim is to evaluate the
      result of insufficient production of pituitary hormones (hypopituitarism),
      excessive production of adenohypophysis hormones (acromegaly, Cushing's disease
      and hyperprolactinemia) and the influence of pituitary tumours in surrounding
      structures (compression syndrome) and to determine the level of perioperative
      risk. Pharmacological suppressive therapy of the hyperfunctional pituitary
      disorders can have significant interactions with drugs used in the perioperative
      period.

PMID- 21879657
TI  - Preoperative preparation of patient with diabetes mellitus.
AB  - The goal of this article is to present the importance of diabetes mellitus as
      comorbidity in patients submitting to different surgical procedures. The results
      of numerous studies that have been presented here showed worst surgical outcome
      in patients with bad diabetes control. This review considers the elements for
      preoperative evaluation and preparation of these patients (former therapy,
      longterm metabolic control, micro and macrovascular complications etc). According
      to existing data, the goals for preoperative preparation and the regimes for
      their achievement have been defined. Also, the regimes for blood glucose controle
      during intraoperative and postoperative period have been evaluated in this
      article.

PMID- 21879658
TI  - Modern concepts of preoperative preparation of patients with thyroid gland
      disease.
AB  - Preoperative evaluation of patients with thyroid land disease, in any kind of
      surgery, should include the possibility of difficult intubation caused by
      thyromegaly, the hormonal status (its disbalance), as well as the screening, and
      therapy of consequences of thyroid imbalance on specific organ systems,
      especially cardiovascular. It is necessary to select the adequate anesthetics and
      other pharmacological agents, according to current hormonal status. It is also
      necessary to select the adequate medications and other therapeutic measures for
      prevention and treatment of possible complications in perioperative period, some
      of which are life-threatening (thyroid storm and mixedema coma).

PMID- 21879659
TI  - Preoperative preparation of patients with hyperparathyroidism as comorbidity.
AB  - Preoperative preparation of patients with hyperarathyroidism planned to be
      operated and/or already operated because of some other disease have specific
      characteristics in function of the type of hyperparathyroidism, primary or
      secondary. In primary hyperparathyroidism, repercussions of pronounced
      hypercalcemia on organs and systems are of essential importance. The most
      important aspect of preoperative preparation of these patients is therefore the
      treatment of hypercalcemia. In patients with secondary hyperparathyroidism as
      comorbidity, calcium level is of lesser importance since it stays mostly within
      reference values. Essential for perioperative preparation of these patients is
      the fact that they have chronic renal insufficiency and usually are on extrarenal
      depuration, so that uremic toxic disorders important for the perioperative course
      should be taken into account. Disorders caused by primary or secondary
      hyperparathyroidism (and terminal chronic renal insufficiency) must be brough to
      so-called "stable state" in elective surgical interventions. Preoperative
      preparation in urgent surgical interventions is focused only on vitally
      endangering consequences of hyperparathyroidism such as hypercalcemic crisis or
      extreme hyperkalemia.

PMID- 21879660
TI  - Contemporary approach to preoperative preparation of patients with adrenal cortex
      hormones dysfunction.
AB  - Preoperative preparation of the patients with adrenal cortex dysfunction is based
      on the careful preoperative evaluation of the type and the severity of the
      disturbance. The dysfunction involving adrenal glands may be: insufficiency
      (severe, mild, expressed) and hyperfunction (hypercorticism and/or
      hyperaldosteronism). If we speak about the patients with limited adrenal reserve
      (Addison's disease, therapeutic glucocorticoid application etc.) they need
      necessary corticosteroid supplementation, during preoperative preparation, as
      well as, during complete perioperative period. Doses needed for the substitution
      are adjusted according to the severity of adrenal insufficiency and according to
      the extent of the planned surgical procedure. Patients with Cushing's syndrome
      (or other form of hypercorticism), as well as, patients with Conn's syndrome (or
      other forms of hyperaldosteronism), do have numerous organ dysfunctions, that are
      significant in preoperative preparation, anesthesia and for the outcome of the
      surgical treatment. Common feature for both of the above syndromes is
      hydroelectrolyte disbalance, with hypokalemia, metabolic alkalosis and
      hypertension. Disturbances related to the adrenal cortex hyperfunction must be
      corrected preoperatively, in order to avoid complications. When we speak about
      hypokalemia it must be promptly corrected even before urgent/vital surgical
      procedure because it may cause severe intraoperative cardiac arrhythmia.

PMID- 21879661
TI  - Preoperative preparation of patients with renal diseases.
AB  - If patients with renal diseases had to undergo surgical intervention, they should
      be prepared in such a way to be in a stable phase of the underlying surgical
      disease, without any infection, euvolemic, with satisfactory blood pressure and
      corrected electrolyte balance. These patients need to be hydrated well before
      intervention, the fall of blood pressure during intervention should be avoided
      and adequate hydration after the intervention must be continued (taking into
      account the condition of the kidneys, heart and age of patient). It is assumed
      that nephrotoxic drugs are to be evaded in renal patients or, if they were
      necessary, the dosage and dosing interval should be adjusted and prolonged,
      respectively. The use of radiographic contrast is not advisable, but if required,
      plentiful hydration will be needed, the least workable contrast dose and, if
      possible, with lower ionic charge and lower osmolarity will be administered. If
      surgical intervention was urgent and if there was not enough time for
      conservative therapy, i.e., correction of electrolytes, volemia, blood pressure
      and higher values of nitrate substances, a renal patient would be temporarily
      dialyzed in the immediate preoperative and postoperative course. Any surgical
      intervention in these patients may aggravate the renal function and bring the
      patient closer to dialysis treatment. Nevertheless, sometimes the benefit of
      surgical treatment for the acute surgical disease is higher (especially if it was
      life-threatening) than the risk of renal function exacerbation and coming closer
      to dialysis.

PMID- 21879662
TI  - Preoperative assessment of patients with end stage renal failure.
AB  - Patients with end stage renal failure (ESRF) present a number of challenges to
      the anesthesiologist. They may be chronically ill and debilitated and have the
      potential for multisystem organ dysfunction. Patients with primary renal disease
      are likely younger and have good cardiopulmonary reserve. Older patients with
      renal failure secondary to diabetes mellitus or hypertension may suffer the
      ravages of diffuse atherosclerosis and heart disease. To safely manage these
      patients we need to understand the benefits and limitations of dialysis, problems
      related with primary disease, pathophysiological effects of ESRF, and the altered
      pharmacology of commonly used anesthetic agents and perioperative medications in
      ESRF. Problems encountered by anesthesiologist in ESRF patients include
      hypertension, ischemic heart disease, congestive heart failure, anemia, metabolic
      acidosis, hyperkaliemia, hyponatremia and circulatory collapse. All surgical
      procedure in patients with ESRF carries significant risk of peri- and
      postoperative complications (mostly cardiovascular) and even fatal outcome.

PMID- 21879663
TI  - Preoperative assessment and preparation of patients with neurologic disorders.
AB  - Ageing of populataion world wide has significant contribution as one of the major
      risk factor for neurodegenerative disorders. The patients with neurodegenerative
      as well as other neuological diseases presented the population with possible
      great need either of small or big surgical intervention. There are several
      important issues in patients with neurological diseases: the nature, disease
      duration, therapy, the patient's ability to live without assistance. Neurological
      disease may become worst by general and regional anesthesia. Stopping therapy may
      lead to worsening of neurological diseases. One of the main common threat is the
      risk of significant cardiorespiratory complications, which is important in
      assessing operational risk, in preoperative preparation and in terms of
      postoperative recovery and outcomes of surgical treatment. This has resulted in
      greater preoperative care by detailed patient history evaluation and examination,
      patient information and informed consent. Besides the effect of the anaesthetic
      technique upon the course of the disease, there is also the interaction of drugs
      administered during anaesthesia and patient medication. Several undiagnosed
      diseases may be disclosed following a surgical/anaesthetic intervention.

PMID- 21879664
TI  - Preoperative assessment and management of patient with psychiatric comorbidity.
AB  - This article explains the most frequent psychiatric disorders such as co
      morbidity in the acute surgical treatment, along with its position and importance
      for the surgical procedure. Besides basic features of these disorders,
      epidemiology and clinical expression, this article holds the latest therapeutic
      approach, side effects, toxicity and drug interactions, during the surgical
      procedure. Frequent postoperative problems, delirium, and postoperative cognitive
      disorders are noted in these patients. To avoid these complications, it is
      recommended to use a mini-mental score examination to re-evaluate the decision
      and indication for high risk surgery patient.

PMID- 21879665
TI  - Preoperative preparation of alcohol and psychoactive substances-addicted
      patients.
AB  - Proper diagnosis of psychoactive substance abuse and addiction, as well as acute
      intoxication, withdrawal syndrome and overdosing are of great importance in
      patients who are preparing for surgical intervention. There are some specific
      details in their preoperative preparation whether they underwent emergency or
      elective surgery. Good knowledge of the characteristics of psychoactive substance
      abuse and addiction, interaction of psychoactive substances and anesthetics and
      any other drugs that could be used in the perioperative period is important
      especially for anastesiologist. In this work we present key issues for
      recognizing theese patients as well as some guidelines for adequate preoperative
      preparation and postoperative care.

PMID- 21879666
TI  - Osteo-articular diseases as comorbidity in non-orthopaedic surgery.
AB  - Osteo-articular diseases have significant presence among general population.
      Osteo-articular disorders can be caused by disease or by trauma. There are many
      osteo-articular diseases which have influence on general state of the organysm
      and on other present diseases in a various level. The influence appears by
      increasing risk of main disease complications, limited movement complicates
      postoperative treatment of main disease and medicament therapy of osteo-articular
      disease sometimes modifies perioperative therapy of main disease. Trauma as
      comorbidity needs urgent care and, in the same time, it is a huge complication
      for the injured condition. Osteoarticular trauma healing usually lasts several
      weeks, so it prolongs the healing of intercurrent surgical disease. Osteo
      articular changes as comorbidity during the acute surgical disease healing need
      proper preoperative preparing, With the aim to minimise perioperative morbidity
      and mortality.

PMID- 21879667
TI  - Preoperative preparation for patients with nutritional disorders.
AB  - Eating disorders are very common today. An increasing number of patients that
      undergo anesthesia and surgery have some nutritional disorder. These disorders
      are very versatile starting from obesity to anorexia. Significant changes in all
      organ systems are present. These pathophysiological changes are increased with
      the duration of the disease. There are many changes in the functioning of the
      cardiovascular system in all these diseases and there are significant.
      Respiratory and ventilatory functions are changed too. There are also many
      endocrine disorders. As a final result, there are many serious biochemical and
      coagulation disorders. These patients are often under some drug treatment.
      Patients could be under psychiatric therapy (psychiatric drugs) and/or could take
      drugs for relieving symptoms related to the pathophysiological changes in
      different organ systems. Preoperative preparation of patients must be detailed.
      All changes must be improved to optimal condition. In addition, it is necessary
      to think about the possible influence of used drugs on the anesthesia.

PMID- 21879668
TI  - Preoperative preparation of geriatric patients.
AB  - There is a continuous increase in the proportion of elderly patients undergoing
      surgical procedures. This review will concentrate on selected topics related to
      elderly care that represent current unresolved and relevant issues for the care
      of the elderly surgical patient including: aging related organ dysfunction,
      perioperative risk assessment of geriatrics patient, preoperative optimization
      and pharmacological support of elderly patient. Additionally, age as a clear risk
      factor for postoperative cognitive dysfunction is also discussed.

PMID- 21879669
TI  - Preoperative evaluation of patients with history of allergy.
AB  - The prevalence of allergic reactions in general opulation shows a constant rise.
      It has been estimated that up to 40% of surgical patients have a positive history
      of some kind of allergy. These patients represent a challenge during
      perioperative evaluation, since they can be exposed to a large variety of drugs
      and substances during surgery and anesthesia. A lot of adverse drug reactions
      show similar clinical presentation with allergic reactions. The latter are
      usually poorly explored since preoperative allergology testing is performed in a
      limited number of patients. Management of patients with history of allergy is
      impeded by the fact that most of allergens cross-react in a manner that is not
      always easy to predict. Allergies can manifest themselves with a broad spectrum
      of clinical symptoms, ranging from mild skin symptoms such as itch and urticaria,
      to a life-threatening anaphylactic reactions followed by hypotension,
      bronchospasm and cardiovascular collapse. Prevention of allergic reactions during
      perioperative period requires detailed history taking in order to identify
      patients at risk, optimization of anesthesia strategy, pharmacological
      premedication and further allergology diagnostic work-up in selected cases.

PMID- 21879670
TI  - Preoperative assesment of the immunocompromised patient.
AB  - In some surgical patients immunosuppression is easily apparent and directly
      caused by known underlying disease or treatment. In others, although induced by
      the underlying disease, immunosuppression may be less obvious. Perioperative
      management of immunocompromised patient is mostly directed by the fact that
      immunosuppression itself does not cause pathology, but does leave the patient
      prone to infection. Immunodeficiency can be broadly characterized as congenital
      (primary) or acquired (secondary). The majority of immune deficiencies that are
      of interest to the anaesthetist are acquired. They can be present both in
      children and adults, in a huge variety of patients that are presented
      preoperatively. Most of them do not require different than usual perioperative
      anaesthetic management. However, in some of them specific aspects of treatment
      should be considered, such as HIV infected, cancer, transplant patients, and
      those scheduled for organ transplantation.

PMID- 21879671
TI  - Preoperative preparation of pregnant women.
AB  - All the elective surgeries are to be avoided during pregnancy and pregnant women
      should undergo only emergency surgical interventions. Pregnancy is associated
      with different physiological changes in the organism, which should be taken into
      account in preparative preparation of the pregnant women. Expanded body fluid
      volume leads to dilutional anemia, however other hematological disorders may be
      present as well. Extreme obesity is a frequent comorbidity, while hypertension is
      associated with the highest risks since it may lead to a life-threatening
      complication--eclampsia. As for other coexisting diseases, urinary tract
      infections and gestational diabetes are the most common as well as
      hyperthyroidism and other diseases that may also develop. The type and severity
      of the acute surgical disease, extensiveness of the planned surgery as well as
      the type of planned anesthesia to be applied, occasionally necessitate, depending
      on the gestational age, termination of pregnancy to be considered. Gynecological
      obstetric consultations are mandatory in all surgical interventions planned in
      pregnant women.

PMID- 21879672
TI  - Rough ride ahead. Moody's sees trouble for THR since swift acquisition.

PMID- 21879673
TI  - Poor ratings. Standard & Poor's report highlights dysfunction in its own realm.

PMID- 21879674
TI  - Feeling the squeeze. Healthcare execs see smaller raises overall, but some still
      net strong increases while others lose ground.

PMID- 21879675
TI  - States with the most ambulatory surgery centers.

PMID- 21879676
TI  - Cosmetic sciences from ancient Persia.

PMID- 21879677
TI  - Brown cosmetics in ancient Egypt.

PMID- 21879678
TI  - The proposal for an imperial pharmaceutical qualification 1929.

PMID- 21879679
TI  - Anticipating sympathomimetic asthma therapy: Henry Hyde Salter (1823-1871).

PMID- 21879680
TI  - RNs share lessons learned in primary care network.

PMID- 21879681
TI  - Assessing caffeine impact on patient health.

PMID- 21879682
TI  - Addictions: preventative practice for professional nurses.

PMID- 21879683
TI  - Social justice: who cares?

PMID- 21879684
TI  - Adding drug to hanging IV bag poses many risks.

PMID- 21879685
TI  - From stack-firing to pyromania: medico-legal concepts of insane arson in British,
      US and European contexts, c. 1800-1913. Part I.
AB  - This article surveys evolving and competing medico-legal concepts of pyromania
      and insane arson. Exploiting evidence from medical jurisprudence, medico-legal
      publications, medical lexicography and case histories, it seeks to explicate the
      key positions in contemporary professional debates concerning arson and mental
      derangement. A major focus is the application of the doctrines of moral and
      partial insanity, monomania, instinctive insanity and irresistible impulse to
      understandings of pyromania and insane arson. The limited extent to which mental
      defect provided a satisfactory diagnosis and exculpatory plea for morbid arson is
      also explored. Additionally, this article compares and contrasts contemporary
      debates about other special manias, especially kleptomania. Part 2 will be
      published in the next issue, History of Psychiatry 21 (4).

PMID- 21879686
TI  - Illnesses of the will in 'pre-psychiatric' times.
AB  - Since its emergence as a medical discipline in its own right, i.e. since the end
      of the eighteenth century, disorders of the will have constituted a major area of
      interest for psychiatrists. But even before then, in 'pre-psychiatric' times so
      to speak, there were occasional descriptions of illnesses of the will or, in the
      nomenclature used at the time,'ambiguous emotional states of minds'.This study
      presents some very early attempts to tackle and explain the problems of amentia
      occulta, manie sons delire and monomania in German literature, concentrating on
      works written from a medical and philosophical perspective. Beginning with the
      differentiation between will and reason, this study explores some concepts in
      which the will was perceived as a possible cause of mental illness and thus
      became a topic of medical interest.

PMID- 21879687
TI  - The face of madness in Romania: the origin of psychiatric photography in Eastern
      Europe.
AB  - In 1870 the Romanian physician Nicolae G. Chernbach published a photographic
      atlas of the main types of mental alienation, a collection of twelve plates
      depicting mentally ill patients from the Marcutza Asylum in Bucharest. Each
      photograph included a diagnosis based on the clinical nosography and theories of
      the physiognomy of insanity acknowledged during the period. The publication of
      the atlas--just a few years after Hugh W. Diamond's initial use of photography
      for this purpose in Britain in the 1850s--means that the photographs were not
      only the first taken in Romania, but among the first photographs of the mentally
      ill. This study provides an insight into the origins of modern clinical
      psychiatry and medical advances in Romania, and the contemporary personalities in
      Romanian and Eastern European medicine.

PMID- 21879688
TI  - From psyche to soma? Changing accounts of antisocial personality disorders in the
      American Journal of Psychiatry.
AB  - The history of psychiatry is often portrayed through the metaphor of a pendulum,
      the profession swinging back and forth between a concern with psyche and soma.
      Recent work critiquing the pendulum metaphor, however, suggests that it does not
      account for the complexity of psychiatry. This article explores the metaphor
      through an analysis of the changing aetiological accounts of personality
      disorders associated with antisocial behaviour advanced in the American Journal
      of Psychiatry from 1950 onwards. It is argued that the social, scientific and
      economic factors which help shape overarching professional trends in psychiatry
      only partly structure personality disorder discourse. If the pendulum swings,
      therefore, not all psychiatrists move with it.

PMID- 21879689
TI  - Psychiatry in Britain, c. 1900.
AB  - At this period, British psychiatrists practised in a climate of opinion that was
      deeply pessimistic, influenced by the views of Henry Maudsley and by the
      accumulation in asylums of incurable patients. The inflexible Lunacy Act of 1890
      tended to encourage chronicity. The terminology both of mental illness and of the
      doctors who dealt with it was uncertain. Management of these disorders was
      intimately involved with the operation of the Poor Law. Neurology, on the other
      hand, carried high prestige and advanced clinically; many patients with neurotic
      disorders came under the care of neurologists. Postgraduate education and
      training in psychiatry was practically non-existent, as was academic psychiatry,
      in contrast notably to Germany, though there was a small professional
      organization.

PMID- 21879690
TI  - The reception of Eugen Bleuler in British psychiatry, 1892-1954.
AB  - This article draws on over 60 years of British medical journals and psychiatry
      textbooks to indicate the chronological stages of the reception of Eugen Bleuler
      in British psychiatry. Bleuler was already well known in Britain before his
      schizophrenia book appeared, with the journals containing numerous references,
      mainly positive, to his work. The psychiatry textbooks, however, were slower to
      integrate his contribution. This paper argues that this was not due to Bleuler's
      placing Freud on a par with Kraepelin, but because of the early negative reaction
      to Kraepelin's dementia praecox concept, despite Bleuler's wider and less ominous
      conception of the illness.

PMID- 21879691
TI  - On the chopping block. Municipal bonds could be seen as part of deficit fix.

PMID- 21879692
TI  - Meeting resistance. Express Scripts-Medco deal called anti-competitive.

PMID- 21879693
TI  - Price stability. No hike expected in Medicare drug plan averages.

PMID- 21879694
TI  - Gun to the head. Debt-ceiling law reminds providers who runs the healthcare show.

PMID- 21879695
TI  - Safety net for needy. Healthcare leaders want providers to put focus on primary
      care.

PMID- 21879696
TI  - An 'open door' for the vulnerable. Even after reform is in place, need for safety
      net providers will be great.

PMID- 21879697
TI  - Total recall. Providers are taking the lead in revamping system for handling
      questionable drugs and medical devices.

PMID- 21879698
TI  - Largest healthcare law firms.

PMID- 21879699
TI  - Still at ground level. Security concerns hinder move into cloud services.

PMID- 21879700
TI  - Inside Pfizer's palace coup. Did CEO Jeff Kindler get pushed out because he was
      shaking up the dysfunctional pharmaceutical giant--or because he was an
      ineffective leader?

PMID- 21879701
TI  - Biodegradable block copolymer micelles with thiol-responsive sheddable coronas.
AB  - Novel sheddable micelles having hydrophilic coronas capable of being shed from
      biodegradable polylactide (PLA) cores by the cleavage of disulfide linkages in
      response to thiols were prepared by aqueous micellization of PLA-based
      amphiphilic block copolymers functionalized with disulfides at block junctions.
      These well-defined copolymers were synthesized by a combination of ring-opening
      polymerization and atom transfer radical polymerization in the presence of a new
      disulfide-functionalized double-head initiator having both terminal OH and Br
      groups. (1)H NMR and GPC results indicate that both polymerizations were well
      controlled with molecular weight distribution as low as M(w)/M(n) < 1.2. Aqueous
      micellization to form core/shell micelles with disulfides at the interface of PLA
      cores and hydrophilic coronas and their thiol-responsive degradation were
      investigated. In the presence of water-soluble thiols, disulfide linkages in the
      micelles were cleaved and hydrophilic coronas were lost, causing PLA cores to
      precipitate due to the loss of colloidal stability. In a biomedical perspective,
      the new sheddable micelles were not cytotoxic and hence biocompatible.

PMID- 21879702
TI  - Concise asymmetric total synthesis of 9-epi-sessilifoliamide J.
AB  - A 10-step asymmetric synthesis of 9-epi-sessilifoliamide J (20), together with
      sessilifoliamide J (6), has been accomplished from the key chiral building block
      11 via a threo-selective vinylogous Mannich reaction and a Ley oxidation-SmI(2)
      mediated coupling lactonization. The absolute configuration of the natural
      sessilifoliamide J was established.

PMID- 21879703
TI  - Synthesis of 6-substituted-4-hydroxy-2-pyridinones via intramolecular ketene
      trapping of functionalized enamine-dioxinones.
AB  - The synthesis of various 6-substituted-4-hydroxy-2-pyridinones is reported. The
      functionalized keto-dioxinones were constructed via a diethylzinc mediated
      crossed Claisen condensation reaction and subsequent enamine formation,
      thermolysis, and cyclization-aromatization providing the pyridinone unit.

PMID- 21879704
TI  - Three-component coupling approach to trachyspic acid.
AB  - Three-component coupling of the lithium enolate of t-BuOAc, silyl glyoxylate, and
      an alpha,beta-unsaturated ketone enables the rapid construction of the trachyspic
      acid carbon skeleton. A 3,4-disubstituted isoxazole is utilized to mask the C7/C9
      dicarbonyl. New enolsilane/nitrile-oxide cycloadditions enable the preparation of
      various 3,4-disubstituted isoxazoles that are challenging to access by other
      means.

PMID- 21879705
TI  - Halide, amide, cationic, manganese carbonylate, and oxide derivatives of
      triamidosilylamine uranium complexes.
AB  - Treatment of the complex [U(Tren(TMS))(Cl)(THF)] [1, Tren(TMS) =
      N(CH(2)CH(2)NSiMe(3))(3)] with Me(3)SiI at room temperature afforded known
      crystalline [U(Tren(TMS))(I)(THF)] (2), which is reported as a new polymorph.
      Sublimation of 2 at 160  degrees C and 10(-6) mmHg afforded the solvent-free
      dimer complex [{U(Tren(TMS))(MU-I)}(2)] (3), which crystallizes in two
      polymorphic forms. During routine preparations of 1, an additional complex
      identified as [U(Cl)(5)(THF)][Li(THF)(4)] (4) was isolated in very low yield due
      to the presence of a slight excess of [U(Cl)(4)(THF)(3)] in one batch. Reaction
      of 1 with one equivalent of lithium dicyclohexylamide or bis(trimethylsilyl)amide
      gave the corresponding amide complexes [U(Tren(TMS))(NR(2))] (5, R = cyclohexyl;
      6, R = trimethylsilyl), which both afforded the cationic, separated ion pair
      complex [U(Tren(TMS))(THF)(2)][BPh(4)] (7) following treatment of the respective
      amides with Et(3)NH.BPh(4). The analogous reaction of 5 with Et(3)NH.BAr(f)(4)
      [Ar(f) = C(6)H(3)-3,5-(CF(3))(2)] afforded, following addition of 1 to give a
      crystallizable compound, the cationic, separated ion pair complex
      [{U(Tren(TMS))(THF)}(2)(MU-Cl)][BAr(f)(4)] (8). Reaction of 7 with K[Mn(CO)(5)]
      or 5 or 6 with [HMn(CO)(5)] in THF afforded [U(Tren(TMS))(THF)(MU-OC)Mn(CO)(4)]
      (9); when these reactions were repeated in the presence of 1,2-dimethoxyethane
      (DME), the separated ion pair [U(Tren(TMS))(DME)][Mn(CO)(5)] (10) was isolated
      instead. Reaction of 5 with [HMn(CO)(5)] in toluene afforded [{U(Tren(TMS))(MU
      OC)(2)Mn(CO)(3)}(2)] (11). Similarly, reaction of the cyclometalated complex
      [U{N(CH(2)CH(2)NSiMe(2)Bu(t))(2)(CH(2)CH(2)NSiMeBu(t)CH(2))}] with [HMn(CO)(5)]
      gave [{U(Tren(DMSB))(MU-OC)(2)Mn(CO)(3)}(2)] [12, Tren(DMSB) =
      N(CH(2)CH(2)NSiMe(2)Bu(t))(3)]. Attempts to prepare the manganocene derivative
      [U(Tren(TMS))MnCp(2)] from 7 and K[MnCp(2)] were unsuccessful and resulted in
      formation of [{U(Tren(TMS))}(2)(MU-O)] (13) and [MnCp(2)]. Complexes 3-13 have
      been characterized by X-ray crystallography, (1)H NMR spectroscopy, FTIR
      spectroscopy, Evans method magnetic moment, and CHN microanalyses.

PMID- 21879707
TI  - Determination of 4(5)-methylimidazole in soy sauce and other foods by LC-MS/MS
      after solid-phase extraction.
AB  - A method for the determination of 4(5)-methylimidazole (4MeI) in naturally brewed
      soy sauce was developed for the first time using solid-phase extraction (SPE) and
      liquid chromatography-tandem mass spectrometry (LC-MS/MS). SPE on silica-based
      reversed-phase cartridges with heptafluorobutyric acid as an ion-pairing reagent
      was used for the efficient cleanup of 4MeI. A multimode ODS column was employed
      for the chromatographic separation. To subtract the matrix effect during LC-MS/MS
      analysis, a standard addition method was used. The levels of 4MeI found in
      naturally brewed soy sauce were extremely low (ranging from <0.002 to 0.023
      MUg/g), whereas those in soy sauces containing caramel color were generally high
      (ranging from 0.43 to 4.8 MUg/g). The method proved to be useful for the analysis
      of 4MeI in other foods such as caramel colors, drinks, and Worcestershire sauce.

PMID- 21879708
TI  - Proteomic analysis of pH and strains dependent protein secretion of Trichoderma
      reesei.
AB  - Bioenergy, particularly biofuel, from lignocellulosic biomass has been considered
      as one of the most promising renewable and sustainable energies. The industrial
      productivity and efficiency of microbial lignocellulolytic enzymes for cellulosic
      biofuel applications are significantly affected by pH of culture condition. This
      study established and compared hydrolytic protein expression profiles of
      Trichoderma reesei QM6a, QM9414, RUT C30 and QM9414MG5 strains at different pH in
      cellulosic culture media. Liquid chromatography-tandem mass spectrometry (LC
      MS/MS) analysis of secretome of T. reesei cultured from pH 3.0-9.0 revealed
      significantly higher hydrolytic protein expressions at acidic pH. The Bray-Curtis
      similarity indices, clustering, and Shannon diversity index elucidated
      differences in protein secretion at different pHs in individuals and among the
      strains. This study demonstrated a comparative lignocellulolytic enzyme secretion
      profile of T. reesei and its mutants at different pHs and provides pH sensitive
      and resistance enzyme targets for industrial lignocellulose hydrolysis.

PMID- 21879706
TI  - Chemical tags for labeling proteins inside living cells.
AB  - To build on the last century's tremendous strides in understanding the workings
      of individual proteins in the test tube, we now face the challenge of
      understanding how macromolecular machines, signaling pathways, and other
      biological networks operate in the complex environment of the living cell. The
      fluorescent proteins (FPs) revolutionized our ability to study protein function
      directly in the cell by enabling individual proteins to be selectively labeled
      through genetic encoding of a fluorescent tag. Although FPs continue to be
      invaluable tools for cell biology, they show limitations in the face of the
      increasingly sophisticated dynamic measurements of protein interactions now
      called for to unravel cellular mechanisms. Therefore, just as chemical methods
      for selectively labeling proteins in the test tube significantly impacted in
      vitro biophysics in the last century, chemical tagging technologies are now
      poised to provide a breakthrough to meet this century's challenge of
      understanding protein function in the living cell. With chemical tags, the
      protein of interest is attached to a polypeptide rather than an FP. The
      polypeptide is subsequently modified with an organic fluorophore or another
      probe. The FlAsH peptide tag was first reported in 1998. Since then, more refined
      protein tags, exemplified by the TMP- and SNAP-tag, have improved selectivity and
      enabled imaging of intracellular proteins with high signal-to-noise ratios.
      Further improvement is still required to achieve direct incorporation of powerful
      fluorophores, but enzyme-mediated chemical tags show promise for overcoming the
      difficulty of selectively labeling a short peptide tag. In this Account, we focus
      on the development and application of chemical tags for studying protein function
      within living cells. Thus, in our overview of different chemical tagging
      strategies and technologies, we emphasize the challenge of rendering the labeling
      reaction sufficiently selective and the fluorophore probe sufficiently well
      behaved to image intracellular proteins with high signal-to-noise ratios. We
      highlight recent applications in which the chemical tags have enabled
      sophisticated biophysical measurements that would be difficult or even impossible
      with FPs. Finally, we conclude by looking forward to (i) the development of high
      photon-output chemical tags compatible with living cells to enable high
      resolution imaging, (ii) the realization of the potential of the chemical tags to
      significantly reduce tag size, and (iii) the exploitation of the modular chemical
      tag label to go beyond fluorescent imaging.

PMID- 21879709
TI  - First-row transition-metal chloride complexes of the wide bite-angle diphosphine
      (iPr)DPDBFphos and reactivity studies of monovalent nickel.
AB  - The diphosphine 4,6-bis(3-diisopropylphosphinophenyl)dibenzofuran (abbreviated as
      (iPr)DPDBFphos) has been metalated with transition metal dichlorides of zinc,
      cobalt, and nickel to yield ((iPr)DPDBFphos)MCl(2) complexes. Within these
      compounds, the diphosphine (iPr)DPDBFphos adapts a wide range of bite angles (115
      to 180 degrees ) as determined by X-ray crystallography. A three-coordinate
      planar Ni(I) species was isolated from the reduction of ((iPr)DPDBFphos)NiCl(2)
      with KC(8). Low-temperature electron paramagnetic resonance (EPR) measurements of
      ((iPr)DPDBFphos)NiCl allow the determination of g values (2.09, 2.14, 2.37) and
      hyperfine coupling constants to two (31)P nuclei, A(iso) = 46 * 10(-4) cm(-1),
      and one (37)Cl/(35)Cl nucleus, A = (12, 0.7, 35) * 10(-4) cm(-1). Density
      functional theory (DFT) studies reveal the nature of the magnetic orbital to be
      d(xy), which has sigma-antibonding and pi(?)-antibonding interactions with the
      phosphorus and chloride atoms, respectively. The monovalent nickel complex reacts
      with substrates containing C-X bonds; and in the case of vinyl chloride, a Ni(II)
      vinyl species ((iPr)DPDBFphos)Ni(CH?CH(2))Cl is generated along with the Ni(II)
      dichloride complex. The monovalent Ni(I) chloride is an active catalyst in the
      Kumada cross-coupling reaction of vinyl chloride and phenyl Grignard reagent.

PMID- 21879710
TI  - Dendrimers to treat rheumatoid arthritis.
AB  - In comparison with linear polymers, dendrimers' multivalency and nanostructure
      confer substantial advantages in drug delivery including rapid cell entry,
      targetability, and easier passage across biological barriers. Previous work has
      shown that phosphorus-containing dendrimers capped with anionic azabisphosphonate
      (ABP) end groups prompt anti-inflammatory activation of human monocytes. By using
      two mouse models of arthritis mimicking human rheumatoid arthritis (RA), Hayder
      et al. recently demonstrated that intravenous injection of dendrimer ABP inhibits
      the secretion of proinflammatory cytokines and osteoclastogenesis--two
      fundamental monocyte-dependent processes of inflammation and bone erosion in RA.
      While available biological therapies for RA target only one of the cytokines
      involved in inflammation or bone erosion, dendrimer ABP, by virtue of its double
      action on both processes in mice, might become a more active and cost-saving
      alternative for RA patients. This Perspective highlights this important
      development and the challenges that lie ahead.

PMID- 21879711
TI  - Ruthenium-catalyzed para-selective oxidative cross-coupling of arenes and
      cycloalkanes.
AB  - A novel, direct para-selective oxidative cross-coupling of benzene derivatives
      with cycloalkanes catalyzed by ruthenium was developed. A wide range of arenes
      bearing electron-withdrawing substituents was functionalized directly with simple
      cycloalkanes with high para-selectivity; arenes with electron-donating groups
      were mainly para-functionalized. Benzoic acid can be used directly.

PMID- 21879712
TI  - Role of the ectodomain serine 275 in shaping the binding pocket of the ATP-gated
      P2X3 receptor.
AB  - ATP-activated P2X3 receptors expressed in nociceptive sensory neurons play an
      important role in pain signaling. Basic properties of this receptor subtype,
      including very strong desensitization, depend on the rate of dissociation of the
      agonist from the binding site. Even though the rough structure of the ATP binding
      site has been proposed on the basis of the X-ray structure of the zebrafish P2X4
      receptor and mutagenesis studies, the fine subunit-specific structural properties
      predisposing the receptor to tight capture of the agonist inside the binding
      pocket have not been elucidated. In this work, by exploring in silico the
      functional role for the left flipper located in the ectodomain region, we
      identified within this loop a candidate residue S275, which could contribute to
      the closure of the agonist-binding pocket. Testing of the S275 mutants using the
      patch-clamp technique revealed a crucial role for S275 in agonist binding and
      receptor desensitization. The S275A mutant showed a reduced rate of onset of
      desensitization and accelerated resensitization and was weakly inhibited by
      nanomolar agonist. Extracellular calcium application produced inhibition instead
      of facilitation of membrane currents. Moreover, some full agonists became only
      partial agonists when applied to the S275A receptor. These effects were stronger
      with the more hydrophobic mutants S275C and S275V. Taken together, our data
      suggest that S275 contributes to the closure of the agonist-binding pocket and
      that effective capture of the agonist provided by the left flipper in calcium
      dependent manner determines the high rate of desensitization, slow recovery, and
      sensitivity to nanomolar agonist of the P2X3 receptor.

PMID- 21879713
TI  - Dual high adhesion surface for water in air and for oil underwater.
AB  - A new type of dual high surface adhesion both in an oil/water/solid system and in
      a water/air/solid system is reported. A walnutlike cuprous iodide (CuI)
      microcrystal surface, which is composed of numerous CuI nanocrystals, shows an
      amphiphobic, highly adhesive surface for water in air and for oil underwater. The
      maximum adhesive force is about 120.3 +/- 1.6 MUN in the air for a water droplet
      and about 23.8 +/- 2.1 MUN underwater for an oil droplet. These findings will
      help us to design novel high adhesive materials in two-phase or multiphase
      mediums.

PMID- 21879714
TI  - Anti-influenza virus polyketides from the acid-tolerant fungus Penicillium
      purpurogenum JS03-21.
AB  - Fractionation of the ethyl acetate extract of an acid-tolerant fungus,
      Penicillium purpurogenum JS03-21, resulted in the isolation of six new compounds,
      purpurquinones A-C (1-3), purpuresters A and B (4 and 5), and 2,6,7-trihydroxy-3
      methylnaphthalene-1,4-dione (6), together with three known compounds, TAN-931
      (7), (-)-mitorubrin (8), and orsellinic acid. The structures of 1-6 were
      elucidated primarily by NMR experiments. The absolute configurations of 1-4 were
      assigned on the basis of CD and NOESY data. Compounds 2-4 and 7 exhibited
      significant antiviral activity against H1N1, with IC50 values of 61.3, 64.0,
      85.3, and 58.6 MUM, respectively.

PMID- 21879715
TI  - A chiroptical photoswitchable DNA complex.
AB  - The interesting structural, electronic, and optical properties of DNA provide
      fascinating opportunities for developing nanoscale smart materials by integrating
      DNA with opto-electronic components. In this article we demonstrate the
      electrostatic binding of an amine-terminated dithienylethene (DET) molecular
      switch to double-stranded synthetic polynucleotides. The DET switch can undergo
      photochemical ring-closure and opening reactions. Circular dichroism (CD) and UV
      vis spectroscopy show that both the open, 1o, and the closed, 1c, forms of the
      switch bind to DNA. Upon addition of DNA to a solution of 1o or 1c, the UV-vis
      spectrum displays a hypochromic effect, indicative of an interaction between the
      switch and the DNA. The chirality of the DNA double-helix is transmitted to the
      switching unit which displays a well-defined CD signal upon supramolecular
      complexation to the DNA. Additionally, the CD signal of the DNA attenuates,
      demonstrating that both components of the complex mutually influence each other's
      structure; the DNA induces chirality in the switch, and the switch modifies the
      structure of the DNA. Modulation of the chiroptical properties of the complex is
      achieved by photochemically switching the DET between its ring open and closed
      isomers. A pH dependence study of the binding shows that when the pH is increased
      the switches lose their binding ability, indicating that electrostatic
      interactions between protonated amines and the negatively charged phosphate
      backbone are the dominant driving force for binding to the DNA. A comparison of
      poly(deoxyguanylic-deoxycytidylic) acid [poly(dGdC)(2)] polynucleotides with
      poly(deoxyadenylic-deoxythymidylic) acid [poly(dAdT)(2)] shows distinct
      differences in the CD spectra of the complexes.

PMID- 21879716
TI  - Secondary water relaxation in a water/dimethyl sulfoxide mixture revealed by
      deuteron nuclear magnetic resonance and dielectric spectroscopy.
AB  - We exploit the potential of a combined dielectric spectroscopy (DS) and deuteron
      nuclear magnetic resonance ((2)H NMR) approach to investigate the molecular
      dynamics in a supercooled 2:1 molar mixture of deuterated water (D(2)O) and
      dimethyl sulfoxide (DMSO). While DS probes the rotational motion of both
      components, application of (2)H NMR allows us to single out the dynamical
      behavior of the water molecules. Combining the results of both methods, we can
      follow the slowdown of the alpha-process of the mixture over more than 10 orders
      of magnitude in time, revealing that the Vogel-Fulcher-Tammann (VFT) equation
      describes well its temperature dependence down to the glass transition
      temperature, T(g) = 146 K. While the (2)H NMR data do not provide evidence for a
      secondary relaxation process in the weakly supercooled regime, they indicate
      that, in the deeply supercooled regime, T(g) <= T <= 160 K, the water molecules
      do show a secondary dynamical process, which is faster and exhibits a weaker
      temperature dependence than the alpha-process of the mixture. Consistently, the
      shape of the dielectric spectra changes in this temperature range. (2)H NMR
      rotational correlation functions reveal that this faster secondary water process
      destroys essentially all orientational correlation. In addition, these data show
      that the water reorientation process is characterized by a mean elementary jump
      angle smaller than 13 degrees . Possible origins of the faster secondary water
      process in the deeply supercooled mixture are discussed.

PMID- 21879717
TI  - Surface plasmon resonances in strongly coupled gold nanosphere chains from
      monomer to hexamer.
AB  - We present experimental data on the light scattering properties of linear chains
      of gold nanoparticles with up to six nanoparticles and an interparticle spacing
      of 1 nm. A red shift of the surface plasmon resonance with increasing chain
      length is observed. An exponential model applied to the experimental data allows
      determination of an asymptotic maximum resonance at a chain length of 10-12
      particles. The optical data are compared with analytical and numerical
      calculation methods (EEM and BEM).

PMID- 21879718
TI  - Random laser based on waveguided plasmonic gain channels.
AB  - A waveguide-plasmonic scheme is constructed by coating the matrix of randomly
      distributed gold nanoisland structures with a layer of dye-doped polymer, which
      provides strong feedback or gain channels for the emission from the dye molecules
      and enables successful running of a random laser. Excellent overlap of the
      plasmonic resonance of the gold nanoislands with the photoluminescence spectrum
      of the dye molecules and the strong confinement mechanism provided by the active
      waveguide layer are the key essentials for the narrow-band and low-threshold
      operation of this random laser. This kind of feedback configuration potentially
      enables directional output from such random lasers. The flexible solution
      processable fabrication of the plasmonic gold nanostructures not only enables
      easy realization of such a random laser but also provides mechanisms for the
      tuning and multicolor operation of the laser emission.

PMID- 21879719
TI  - Particle size, shape and activity for photocatalysis on titania anatase
      nanoparticles in aqueous surroundings.
AB  - TiO(2) nanoparticles have been widely utilized in photocatalysis, but the atomic
      level understanding on their working mechanism falls much short of expectations.
      In particular, the correlation between the particle structure and the
      photocatalytic activity is not established yet, although it was observed that the
      activity is sensitive to the particle size and shape. This work, by investigating
      a series of TiO(2) anatase nanoparticles with different size and shape as the
      photocatalyst for water oxidation, correlates quantitatively the particle size
      and shape with the photocatalytic activity of the oxygen evolution reaction
      (OER). Extensive density functional theory (DFT) calculations combined with the
      periodic continuum solvation model have been utilized to compute the electronic
      structure of nanoparticles in aqueous solution and provide the reaction
      energetics for the key elementary reaction. We demonstrate that the equilibrium
      shape of nanoparticle is sensitive to its size from 1 to 30 nm, and the sharp
      crystals possess much higher activity than the flat crystals in OER, which in
      combination lead to the morphology dependence of photocatalytic activity. The
      conventionally regarded quantum size effect is excluded as the major cause. The
      physical origin for the shape-activity relationship is identified to be the
      unique spatial separation/localization of the frontier orbitals in the sharp
      nanoparticles, which benefits the adsorption of the key reaction intermediate
      (i.e., OH) in OER on the exposed five-coordinated Ti of {101} facet. The
      theoretical results here provide a firm basis for maximizing photocatalytic
      activity via nanostructure engineering and are also of significance for
      understanding photocatalysis on nanomaterials in general.

PMID- 21879720
TI  - Conformational switching immobilized hairpin DNA probes following subsequent
      expanding of gold nanoparticles enables visual detecting sequence-specific DNA.
AB  - A simple, rapid, and sensitive method for visual detection of sequence-specific
      DNA was developed using hairpin DNA as the recognition element and hydroxylamine
      enlarged gold nanoparticles (Au-NPs) as the signal producing component. In the
      assay, we employed a hairpin DNA probe dually labeled with amine and biotin at
      the 5'- and 3'-end, respectively. The probe was coupled with reactive N
      oxysuccinnimide in a DNA-bind 96-well plate. Without the target DNA, the
      immobilized hairpin probe was in a "closed" state, which kept the streptavidin
      gold off the biotin. The hybridization between the loop sequence and the target
      broke the short stem duplex upon approaching the target DNA. Consequently, biotin
      was forced away from the 96-well plate surface and available for conjugation with
      the streptavidin-gold. The hybridization could be detected visually after the
      HAuCl(4)-NH(2)OH redox reaction catalyzed by the Au-NPs. Under the optimized
      conditions, the visual DNA sensor could detect as low as 100 amol of DNA targets
      with excellent differentiation ability and even a single-base mismatch.

PMID- 21879721
TI  - Cross-talk among intracellular signaling pathways mediates the diphenyl
      ditelluride actions on the hippocampal cytoskeleton of young rats.
AB  - In the present report, we showed that diphenyl ditelluride (PhTe)(2) induced in
      vitro hyperphosphorylation of glial fibrillary acidic protein (GFAP), vimentin
      and neurofilament (NF) subunits in hippocampus of 21 day-old rats.
      Hyperphosphorylation was dependent on L-voltage dependent Ca(2+) channels (L
      VDCC), N-methyl-d-aspartate (NMDA) and metabotropic glutamate receptors, as
      demonstrated by the specific inhibitors verapamil, DL-AP5 and MCPG, respectively.
      Also, dantrolene, a ryanodine channel blocker, EGTA and Bapta-AM, extra and
      intracellular Ca(2+) chelators respectively, totally prevented this effect.
      Activation of metabotropic glutamate receptors by (PhTe)(2) upregulates
      phospholipase C (PLC), producing inositol 1, 4, 5-trisphosphate (IP(3)) and
      diacylglycerol (DAG). Therefore, high Ca(2+) levels and DAG directly activate
      Ca(2+)/calmodulin-dependent protein kinase (PKCaMII) and protein kinase C (PCK),
      resulting in the hyperphosphorylation of Ser-57 in the carboxyl-terminal tail
      domain of the low molecular weight NF subunit (NF-L). Also, the activation of
      Erk1/2, and p38MAPK resulted in hyperphosphorylation of KSP repeats of the medium
      molecular weight NF subunit (NF-M). It is noteworthy that PKCaMII and PKC
      inhibitors prevented (PhTe)(2)-induced Erk1/2MAPK and p38MAPK activation as well
      as hyperphosphorylation of KSP repeats on NF-M, suggesting that PKCaMII and PKC
      could be upstream of this activation. Taken together, our results highlight the
      role of Ca(2+) as a mediator of the (PhTe)(2)-elicited signaling targeting
      specific phosphorylation sites on IF proteins of neural cells of rat hippocampus.
      Interestingly, this action shows a significant cross-talk among signaling
      pathways elicited by (PhTe)(2), connecting glutamate metabotropic cascade with
      activation of Ca(2+) channels. The extensively phosphorylated amino- and carboxyl
      terminal sites could explain, at least in part, the neural dysfunction
      associated with (PhTe)(2) exposure.

PMID- 21879723
TI  - Self-assembly and orientation of hydrogen-bonded oligothiophene polymorphs at
      liquid-membrane-liquid interfaces.
AB  - One of the challenges in organic systems with semiconducting function is the
      achievement of molecular orientation over large scales. We report here on the use
      of self-assembly kinetics to control long-range orientation of a quarterthiophene
      derivative designed to combine intermolecular pi-pi stacking and hydrogen bonding
      among amide groups. Assembly of these molecules in the solution phase is
      prevented by the hydrogen-bond-accepting solvent tetrahydrofuran, whereas
      formation of H-aggregates is facilitated in toluene. Rapid evaporation of solvent
      in a solution of the quarterthiophene in a 2:1:1 mixture of 1,4
      dioxane/tetrahydrofuran/toluene leads to self-assembly of kinetically trapped
      mats of bundled fibers. In great contrast, slow drying in a toluene atmosphere
      leads to the homogeneous nucleation and growth of ordered structures shaped as
      rhombohedra or hexagonal prisms depending on concentration. Furthermore,
      exceedingly slow delivery of toluene from a high molecular weight polymer
      solution into the system through a porous aluminum oxide membrane results in the
      growth of highly oriented hexagonal prisms perpendicular to the interface. The
      amide groups of the compound likely adsorb onto the polar aluminum oxide surface
      and direct the self-assembly pathway toward heterogeneous nucleation and growth
      to form hexagonal prisms. We propose that the oriented prismatic polymorph
      results from the synergy of surface interactions rooted in hydrogen bonding on
      the solid membrane and the slow kinetics of self-assembly. These observations
      demonstrate how self-assembly conditions can be used to guide the supramolecular
      energy landscape to generate vastly different structures. These fundamental
      principles allowed us to grow oriented prismatic assemblies on transparent indium
      doped tin oxide electrodes, which are of interest in organic electronics.

PMID- 21879722
TI  - Mitochondrial-nuclear communication by prohibitin shuttling under oxidative
      stress.
AB  - Mitochondrial-nuclear communication is critical for maintaining mitochondrial
      activity under stress conditions. Adaptation of the mitochondrial-nuclear network
      to changes in the intracellular oxidation and reduction milieu is critical for
      the survival of retinal and retinal pigment epithelial (RPE) cells, in relation
      to their high oxygen demand and rapid metabolism. However, the generation and
      transmission of the mitochondrial signal to the nucleus remain elusive.
      Previously, our in vivo study revealed that prohibitin is upregulated in the
      retina, but downregulated in RPE cells in the aging and diabetic model. In this
      study, the functional role of prohibitin in the retina and RPE cells was examined
      using biochemical methods, including a lipid binding assay, two-dimensional gel
      electrophoresis, immunocytochemistry, Western blotting, and a knockdown approach.
      Protein depletion by siRNA characterized prohibitin as an anti-apoptotic molecule
      in mitochondria, while the lipid binding assay demonstrated subcellular
      communication between mitochondria and the nucleus under oxidative stress. The
      changes in the expression and localization of mitochondrial prohibitin triggered
      by reactive oxygen species are crucial for mitochondrial integrity. We propose
      that prohibitin shuttles between mitochondria and the nucleus as an anti
      apoptotic molecule and a transcriptional regulator in a stress environment in the
      retina and RPE cells.

PMID- 21879724
TI  - From near-field to far-field coupling in the third dimension: retarded
      interaction of particle plasmons.
AB  - We study the transition from the near-field to the far-field coupling regime of
      particle plasmons in a three-dimensional geometry. In the far-field regime,
      retardation plays the dominant role and the plasmonic resonances are radiatively
      coupled. When the spatial arrangement of the oscillators is matched to their
      resonance wavelength, superradiant-like effects are observed.

PMID- 21879725
TI  - Dissolved organic carbon enhances the mass transfer of hydrophobic organic
      compounds from nonaqueous phase liquids (NAPLs) into the aqueous phase.
AB  - The hypothesis that dissolved organic carbon (DOC) enhances the mass transfer of
      hydrophobic organic compounds from nonaqueous phase liquids (NAPLs) into the
      aqueous phase above that attributable to dissolved molecular diffusion alone was
      tested. In controlled experiments, mass transfer rates of five NAPL-phase PAHs
      (log K(OW) 4.15-5.39) into the aqueous phase containing different concentrations
      of DOC were measured. Mass transfer rates were increased by up to a factor of 4
      in the presence of DOC, with the greatest enhancement being observed for more
      hydrophobic compounds and highest DOC concentrations. These increases could not
      be explained by dissolved molecular diffusion alone, and point to a parallel DOC
      mediated diffusive pathway. The nature of the DOC-mediated diffusion pathway as a
      function of the DOC concentration and PAH sorption behavior to the DOC was
      investigated using diffusion-based models. The DOC-enhanced mass transfer of NAPL
      phase hydrophobic compounds into the aqueous phase has important implications for
      their bioremediation as well as bioconcentration and toxicity.

PMID- 21879726
TI  - Diverse metabolic profiles of a Streptomyces strain isolated from a hyper-arid
      environment.
AB  - The metabolic profile of Streptomyces sp. strain C34, isolated from the Chilean
      hyper-arid Atacama Desert soil, is dependent on the culture media used for its
      growth. The application of an OSMAC approach on this strain using a range of
      cultivation media resulted in the isolation and identification of three new
      compounds from the rare class of 22-membered macrolactone polyketides, named
      chaxalactins A-C (1-3). In addition, the known compounds deferroxamine E (4),
      hygromycin A (5), and 5"-dihydrohygromycin A (6) were detected. The isolated
      compounds were characterized by NMR spectroscopy and accurate mass spectrometric
      analysis. Compounds 1-3 displayed strong activity against Gram-positive but weak
      activity Gram-negative strains tested.

PMID- 21879727
TI  - Efficient copper-catalyzed S-vinylation of thiols with vinyl halides.
AB  - The synthesis of vinyl sulfides through the coupling reaction of thiols with
      vinyl iodides, bromides, and chlorides is described. The thiols can couple with
      aryl iodides in the presence of only 0.5 mol % Cu(2)O without the need for an
      ancillary ligand. In the presence of 5 mol % of Cu(2)O and 10 mol % 1,10
      phenanthroline as the ligand, the more challenging alkyl vinyl bromides can also
      be coupled with thiols, giving the vinyl sulfides in good to excellent yields.

PMID- 21879728
TI  - Diastereo- and enantioselective conjugate addition of 3-substituted oxindoles to
      nitroolefins catalyzed by a chiral Ni(OAc)2-diamine complex under mild
      conditions.
AB  - A simple catalyst system assembled from an enantiomerically pure diamine ligand
      and Ni(OAc)(2) efficiently generates chiral metal enolates derived from 3
      substituted oxindoles bearing an N-1 carbonyl group. The enolates smoothly
      undergo diastereo- and enantioselective conjugate addition to a wide range of
      nitroolefins under mild reaction conditions, furnishing 3,3-disubstituted
      oxindole products bearing two vicinal quaternary/tertiary stereocenters in 74-95%
      yields and 60:40 to 99:1 dr, 71-97% ee.

PMID- 21879729
TI  - Imaging the hidden modes of ultrathin plasmonic strip antennas by
      cathodoluminescence.
AB  - We perform spectrally resolved cathodoluminescence (CL) imaging nanoscopy using a
      30 keV electron beam to identify the resonant modes of an ultrathin (20 nm),
      laterally tapered plasmonic Ag nanostrip antenna. We resolve with deep
      subwavelength resolution four antenna resonances (resonance orders m = 2-5) that
      are ascribed to surface plasmon polariton standing waves that are confined on the
      strip. We map the local density of states on the strip surface and show that it
      has contributions from symmetric and antisymmetric surface plasmon polariton
      modes, each with a very different mode index. This work illustrates the power of
      CL experiments that can visualize hidden modes that for symmetry reasons have
      been elusive in optical light scattering experiments.

PMID- 21879730
TI  - Compositional variability in conventional and glyphosate-tolerant soybean
      (Glycine max L.) varieties grown in different regions in Brazil.
AB  - The compositions of a diverse range of commercially available conventional and
      genetically modified (GM; glyphosate-tolerant) soybean varieties from maturity
      groups 8 and 5, respectively, grown in the northern and southern soybean regions
      of Brazil during the 2007-2008 and 2008-2009 growing seasons were compared.
      Compositional analyses included measurement of essential macro- and
      micronutrients, antinutrients, and selected secondary metabolites in harvested
      seed as well as measurement of proximates in both forage and harvested seed.
      Statistical comparisons utilized a mixed analysis of variance model to evaluate
      the relative contributions of growing season, soybean growing region, production
      site, phenotype (GM or conventional), and variety. The study highlighted
      extensive variability in the overall data set particularly for components such as
      fatty acids, vitamin E, and isoflavones. There were few differences between the
      GM and non-GM populations, and most of the variability in the data set could be
      attributed to regional and variety differences. Overall, the results were
      consistent with the expanding literature on the lack of any meaningful impact of
      transgene insertion on crop composition.

PMID- 21879731
TI  - CpG hypermethylation of the C-myc promoter by dsRNA results in growth
      suppression.
AB  - Deregulation of the c-myc proto-oncogene plays an important role in
      carcinogenesis. It is, therefore, commonly found to be overexpressed in various
      types of tumors. Downregulation of c-myc expression assumes great importance in
      tumor therapy because of its ability to promote and maintain cancer stem cells.
      Apart from post-transcriptional gene silencing (PTGS), siRNAs have also been
      shown to cause transcriptional gene silencing (TGS) through epigenetic
      modifications of a gene locus. This approach can potentially be used to silence
      genes for longer periods and at a much lesser dosage than PTGS. In this study, we
      have examined the effect of transfection of a novel siRNA directed against a CpG
      island encompassing the CT-I(2) region in the P2 promoter of c-myc in U87MG and
      other cell lines. Transient transfection with this siRNA resulted in c-myc
      promoter CpG hypermethylation and decreased expression of c-myc (both mRNA and
      protein) and its downstream targets. A decrease was also observed in the
      expression of some stemness markers (oct-4 and nanog). Stable transfection also
      confirmed the promoter CpG hypermethylation and reduced c-myc expression along
      with reduced cell proliferation and an increase in apoptosis and senescence. A
      significant decrease in c-myc levels was also observed in three other cancer cell
      lines after transient transfection under similar conditions. Thus this novel
      siRNA has the capability of becoming an effective therapeutic tool in
      malignancies with overexpression of c-myc and may be of particular use in the
      eradication of recalcitrant cancer stem cells.

PMID- 21879732
TI  - Semisynthesis of fluorescent metabolite sensors on cell surfaces.
AB  - Progress in understanding signal transduction and metabolic pathways is hampered
      by a shortage of suitable sensors for tracking metabolites, second messengers,
      and neurotransmitters in living cells. Here we introduce a class of rationally
      designed semisynthetic fluorescent sensor proteins, called Snifits, for measuring
      metabolite concentrations on the cell surface of mammalian cells. Functional
      Snifits are assembled on living cells through two selective chemical labeling
      reactions of a genetically encoded protein scaffold. Our best Snifit displayed
      fluorescence intensity ratio changes on living cells significantly higher than
      any previously reported cell-surface-targeted fluorescent sensor protein. This
      work establishes a generally applicable and rational strategy for the generation
      of cell-surface-targeted fluorescent sensor proteins for metabolites of interest.

PMID- 21879733
TI  - Cooperativity between S...pi and Rg...pi in the OCS...C6H6...Rg (Rg = He, Ne, Ar,
      and Kr) van der Waals complexes.
AB  - The complexes OCS...C(6)H(6), C(6)H(6)...Rg, and OCS...C(6)H(6)...Rg (Rg = He,
      Ne, Ar, and Kr) have been studied by means of MP2 calculations and QTAIM
      analyses. The optimized geometries of the title complexes have C(6v) symmetry.
      The intermolecular interactions in the OCS...C(6)H(6)...Rg complexes are
      comparatively stronger than that in the OCS...C(6)H(6) complex, which prove that
      the He, Ne, Ar, and Kr atoms have the ability to form weak bonds with the benzene
      molecule. In QTAIM studies, the pi-electron density of benzene was separated from
      the total electron density. The molecular graphs and topological parameters of
      the OCS...piC(6)H(6), piC(6)H(6)...Rg, and OCS...piC(6)H(6)...Rg complexes
      indicate that the interactions are mainly attributed to the electron density
      provided by the pi-bonding electrons of benzene and the top regions of the S and
      Rg atoms. Charge transfer is observed from the benzene molecule to SCO/Rg in the
      formation of the OCS...C(6)H(6), C(6)H(6)...Rg, and OCS...C(6)H(6)...Rg
      complexes. Molecular electrostatic potential (MEP) analyses suggest that the
      electrostatic energy plays a pivotal role in these intermolecular interactions.

PMID- 21879734
TI  - Large shift in source of fine sediment in the upper Mississippi river.
AB  - Although sediment is a natural constituent of rivers, excess loading to rivers
      and streams is a leading cause of impairment and biodiversity loss. Remedial
      actions require identification of the sources and mechanisms of sediment supply.
      This task is complicated by the scale and complexity of large watersheds as well
      as changes in climate and land use that alter the drivers of sediment supply.
      Previous studies in Lake Pepin, a natural lake on the Mississippi River, indicate
      that sediment supply to the lake has increased 10-fold over the past 150 years.
      Herein we combine geochemical fingerprinting and a suite of geomorphic change
      detection techniques with a sediment mass balance for a tributary watershed to
      demonstrate that, although the sediment loading remains very large, the dominant
      source of sediment has shifted from agricultural soil erosion to accelerated
      erosion of stream banks and bluffs, driven by increased river discharge. Such
      hydrologic amplification of natural erosion processes calls for a new approach to
      watershed sediment modeling that explicitly accounts for channel and floodplain
      dynamics that amplify or dampen landscape processes. Further, this finding
      illustrates a new challenge in remediating nonpoint sediment pollution and
      indicates that management efforts must expand from soil erosion to factors
      contributing to increased water runoff.

PMID- 21879735
TI  - Activity and safety of synthetic lectins based on benzoboroxole-functionalized
      polymers for inhibition of HIV entry.
AB  - Lectins derived from plant and microbial sources constitute a vital class of
      entry inhibitors that target the oligomannose residues on the HIV envelope gp120.
      Despite their potency and specificity, success of lectin-based entry inhibitors
      may be impeded by high manufacturing costs, formulation and potential
      mitogenicity. Therefore, there exists a gap in the HIV microbicides pipeline that
      underscores the need for mass producible, synthetic, broad-spectrum, and
      biocomptabile inhibitors of HIV entry. Here, we present the development of a
      polymeric synthetic lectin, based on benzoboroxole (BzB), which exhibits weak
      affinity (~25 M(-1)) for nonreducing sugars, similar to those found on the HIV
      envelope. High molecular weight BzB-functionalized polymers demonstrated
      antiviral activity that increased with an increase in ligand density and
      molecular weight of the polymer construct, revealing that polyvalency improves
      activity. Polymers showed significant increase in activity from 25 to 75 mol %
      BzB functionalization with EC(50) of 15 MUM and 15 nM, respectively. A further
      increase in mole functionalization to 90% resulted in an increase of the EC(50)
      (59 +/- 5 nM). An increase in molecular weight of the polymer at 50 mol % BzB
      functionalization showed a gradual but significant increase in antiviral
      activity, with the highest activity seen with the 382 kDa polymer (EC(50) of 1.1
      +/- 0.5 nM in CEM cells and 11 +/- 3 nM in TZM-bl cells). Supplementing the
      polymer backbone with 10 mol % sulfonic acid not only increased the aqueous
      solubility of the polymers by at least 50-fold but also demonstrated a
      synergistic increase in anti-HIV activity (4.0 +/- 1.5 nM in TZM-bl cells),
      possibly due to electrostatic interactions between the negatively charged polymer
      backbone and the positively charged V3-loop in the gp120. The benzoboroxole
      sulfonic acid copolymers showed no decrease in activity in the presence of a
      seminal concentration of fructose (p > 0.05). Additionally, the copolymers
      exhibit minimal, if any, effect on the cellular viability, barrier properties, or
      cytokine levels in human reconstructed ectocervical tissue after 3 days of
      repeated exposure and did not show pronounced activity against a variety of other
      RNA and DNA viruses.

PMID- 21879737
TI  - Experimental assessment of the vibration-reorientation contribution to liquid
      crystal NMR dipolar couplings: the case of tetramethylallene dissolved in a
      nematic mesophase.
AB  - In the present paper, the peculiar orientational behavior, studied by liquid
      crystal NMR (LXNMR) spectroscopy, of the D(2d) symmetry quasi-spherical molecule
      of tetramethylallene (TMA) dissolved in the nematic solvent I52 is exploited to
      attempt a quantitative experimental assessment of the correlation between
      molecular vibrations and overall rotations in weakly oriented molecules. The
      analysis of the very small D(HH) and (1)D((13)C-H) dipolar couplings, available
      from the natural abundance LXNMR spectra of TMA at different temperatures, allows
      for a derivation leading (by making a few approximations) to the quantification
      of the vibration-reorientation (also called nonrigid) contribution affecting the
      observed direct (1)D((13)C-H) dipolar coupling. The obtained results show that,
      under the particular conditions of the studied system (very weak orientational
      ordering of a highly symmetric molecule), this contribution is particularly
      important, in order to reproduce the whole value of the "observed" dipolar
      coupling. This issue is discussed and commented on at length in the work, also,
      by making reference to the analogy with perfectly symmetric molecules (such as
      methane and analogues) dissolved in liquid crystalline phases.

PMID- 21879736
TI  - Human pluripotent stem cell-based approaches for myocardial repair: from the
      electrophysiological perspective.
AB  - Heart diseases are a leading cause of mortality worldwide. Terminally
      differentiated adult cardiomyocytes (CMs) lack the innate ability to regenerate.
      Their malfunction or significant loss can lead to conditions from cardiac
      arrhythmias to heart failure. For myocardial repair, cell- and gene-based
      therapies offer promising alternatives to donor organ transplantation. Human
      embryonic stem cells (hESCs) can self-renew while maintaining their pluripotency.
      Direct reprogramming of adult somatic cells to become pluripotent hES-like cells
      (also known as induced pluripotent stem cells or iPSCs) has been achieved. Both
      hESCs and iPSCs have been successfully differentiated into genuine human CMs. In
      this review, we describe our current knowledge of the structure-function
      properties of hESC/iPSC-CMs, with an emphasis on their electrophysiology and
      Ca(2+) handling, along with the hurdles faced and potential solutions for
      translating into clinical and other applications (e.g., disease modeling,
      cardiotoxicity and drug screening).

PMID- 21879739
TI  - Highly efficient continuous flow reactions using singlet oxygen as a "green"
      reagent.
AB  - Described is a new method for the efficient in situ production of singlet oxygen
      in a simple continuous flow photochemical reactor. The extremely large
      interfacial area generated by running the biphasic mixture in a narrow channel at
      a high flow rate ensures high throughput as well as fast and efficient oxidation
      of various alkenes, 1,3-dienes, and thioethers on a preparative scale.

PMID- 21879738
TI  - Identification of CrkL-SH3 binding proteins from embryonic murine brain:
      implications for Reelin signaling during brain development.
AB  - The Crk and Crk-like (CrkL) adaptor proteins play important roles in numerous
      signaling pathways, bridging tyrosine kinase substrates to downstream signaling
      effectors by virtue of their phosphotyrosine-binding SH2 domains and their
      effector-binding SH3 domains. Critical to understanding the diverse roles of
      Crk/CrkL is the identification of tissue- and signal-specific tyrosine
      phosphorylated substrates to which they are recruited and the tissue-specific
      effector proteins they chaperone into signaling complexes. Crk and CrkL are known
      biochemically and genetically to be essential mediators of Reelin/Disabled-1
      (Dab1) signaling, which governs proper mammalian brain development. Multimeric
      Reelin clusters its receptors as well as the receptor-bound intracellular
      scaffolding protein Dab1. Clustering induces Fyn/Src-dependent Dab1 tyrosine
      phosphorylation, which recruits Crk/CrkL and SH3-bound effectors. Previously, 21
      Crk/CrkL-SH3 binding proteins were identified from diverse cell types. We present
      here the proteomic identification of 101 CrkL-SH3 binding proteins from embryonic
      murine brain. The identified proteins are enriched in the Crk/CrkL-SH3 binding
      motif and signaling activities regulating cell adhesion and motility. These
      results suggest Reelin-induced Dab1 tyrosine phosphorylation may generate a
      multifaceted signaling scaffold containing a rich array of Crk/CrkL-SH3 binding
      effectors and may explain a growing diversity of cellular activities suggested to
      be influenced by Reelin/Dab1 signaling.

PMID- 21879740
TI  - Experimental and theoretical studies on the radical-cation-mediated imino-Diels
      Alder reaction.
AB  - The feasibility of an electron transfer imino-Diels-Alder reaction between N
      benzylideneaniline and arylalkenes in the presence of a pyrylium salt as a
      photosensitizer has been demonstrated by a combination of product studies, laser
      flash photolysis (LFP), and DFT theoretical calculations. A stepwise mechanism
      involving two intermediates and two transition states is proposed.

PMID- 21879741
TI  - Microbially mediated mineral carbonation: roles of phototrophy and heterotrophy.
AB  - Ultramafic mine tailings from the Diavik Diamond Mine, Canada and the Mount Keith
      Nickel Mine, Western Australia are valuable feedstocks for sequestering CO2 via
      mineral carbonation. In microcosm experiments, tailings were leached using
      various dilute acids to produce subsaline solutions at circumneutral pH that were
      inoculated with a phototrophic consortium that is able to induce carbonate
      precipitation. Geochemical modeling of the experimental solutions indicates that
      up to 2.5% and 16.7% of the annual emissions for Diavik and Mount Keith mines,
      respectively, could be sequestered as carbonate minerals and phototrophic
      biomass. CO2 sequestration rates are mainly limited by cation availability and
      the uptake of CO2. Abundant carbonate mineral precipitation occurred when
      heterotrophic oxidation of acetate acted as an alternative pathway for CO2
      delivery. These experiments highlight the importance of heterotrophy in producing
      sufficient DIC concentrations while phototrophy causes alkalinization of waters
      and produces biomass (fatty acids = 7.6 wt.%), a potential feedstock for biofuel
      production. Tailings storage facilities could be redesigned to promote CO2
      sequestration by directing leachate waters from tailings piles into specially
      designed ponds where carbonate precipitation would be mediated by both chemical
      and biological processes, thereby storing carbon in stable carbonate minerals and
      potentially valuable biomass.

PMID- 21879742
TI  - Cryoflotation: densities of amorphous and crystalline ices.
AB  - We present an experimental method aimed at measuring mass densities of solids at
      ambient pressure. The principle of the method is flotation in a mixture of liquid
      nitrogen and liquid argon, where the mixing ratio is varied until the solid
      hovers in the liquid mixture. The temperature of such mixtures is in the range of
      77-87 K, and therefore, the main advantage of the method is the possibility of
      determining densities of solid samples, which are instable above 90 K. The
      accessible density range (~0.81-1.40 g cm(-3)) is perfectly suitable for the
      study of crystalline ice polymorphs and amorphous ices. As a benchmark, we here
      determine densities of crystalline polymorphs (ices I(h), I(c), II, IV, V, VI,
      IX, and XII) by flotation and compare them with crystallographic densities. The
      reproducibility of the method is about +/-0.005 g cm(-3), and in general, the
      agreement with crystallographic densities is very good. Furthermore, we show
      measurements on a range of amorphous ice samples and correlate the density with
      the d spacing of the first broad halo peak in diffraction experiments. Finally,
      we discuss the influence of microstructure, in particular voids, on the density
      for the case of hyperquenched glassy water and cubic ice samples prepared by
      deposition of micrometer-sized liquid droplets.

PMID- 21879743
TI  - Artificial sweetener sucralose in U.S. drinking water systems.
AB  - The artificial sweetener sucralose has recently been shown to be a widespread of
      contaminant of wastewater, surface water, and groundwater. In order to understand
      its occurrence in drinking water systems, water samples from 19 United States
      (U.S.) drinking water treatment plants (DWTPs) serving more than 28 million
      people were analyzed for sucralose using liquid chromatography tandem mass
      spectrometry (LC-MS/MS). Sucralose was found to be present in source water of 15
      out of 19 DWTPs (47-2900 ng/L), finished water of 13 out of 17 DWTPs (49-2400
      ng/L) and distribution system water of 8 out of the 12 DWTPs (48-2400 ng/L)
      tested. Sucralose was only found to be present in source waters with known
      wastewater influence and/or recreational usage, and displayed low removal (12%
      average) in the DWTPs where finished water was sampled. Further, in the subset of
      DWTPs with distribution system water sampled, the compound was found to persist
      regardless of the presence of residual chlorine or chloramines. In order to
      understand intra-DWTP consistency, sucralose was monitored at one drinking water
      treatment plant over an 11 month period from March 2010 through January 2011, and
      averaged 440 ng/L in the source water and 350 ng/L in the finished water. The
      results of this study confirm that sucralose will function well as an indicator
      compound for anthropogenic influence on source, finished drinking and
      distribution system (i.e., tap) water, as well as an indicator compound for the
      presence of other recalcitrant compounds in finished drinking water in the U.S.

PMID- 21879744
TI  - High-field dipolar electron paramagnetic resonance (EPR) spectroscopy of
      nitroxide biradicals for determining three-dimensional structures of
      biomacromolecules in disordered solids.
AB  - We consider the state-of-the-art capabilities and future perspectives of electron
      spin triangulation by high-field/high-frequency dipolar electron paramagnetic
      resonance (EPR) techniques designed for determining the three-dimensional
      structure of large supra-molecular complexes dissolved in disordered solids.
      These techniques combine double site-directed spin labeling (SDSL) with
      orientation-resolving pulsed electron-electron double resonance (PELDOR)
      spectroscopy. In particular, we appraise the prospects of angular triangulation,
      which extends the more familiar distance triangulation. As a model case for spin
      labeled proteins, the three-dimensional structures of two nitroxide biradicals
      with rather stiff bridging blocks and deuterated nitroxide headgroups have been
      derived. To this end we applied 95 GHz high-field electron dipolar EPR
      spectroscopy with the microwave pulse-sequence configurations for PELDOR and
      relaxation-induced dipolar modulation enhancement (RIDME). Various specific
      spectroscopic strategies are discussed to overcome the problems of overlapping
      spectra of the chemically identical nitroxide labels when attached to
      macromolecular systems. We conclude that due to the high detection sensitivity
      and spectral resolution the combination of SDSL with high-field RIDME/PELDOR
      stands out as an extremely powerful tool for 3D structure determination of large
      disordered systems. The approach compares favorably with other structure
      determining magnetic-resonance methods. This holds true both for stable and
      transient radical-pair states. Angular constraints are provided in addition to
      distance constraints obtained for the same sample. Thereby, the number of
      necessary distance constraints is strongly reduced. Since each measurement of a
      distance constraint requires an additional doubly spin-labeled sample, the
      reduction of necessary distance constraints is another appealing aspect of
      orientation-resolving EPR spin triangulation for protein structure determination.

PMID- 21879745
TI  - Survey of polyphenol constituents in grapes and grape-derived products.
AB  - A rapid and comprehensive qualitative method has been developed to characterize
      the different classes of polyphenols, such as anthocyanins, flavonols, phenolic
      acids, and flavanols/proanthocyanidins, in grape products. The detection was
      achieved by two runs with the same LC gradient in different MS ionization modes
      and mobile phase modifiers (positive ionization mode and 0.4% trifluoroacetic
      acid for anthocyanins and flavonols; negative ionization mode and 0.1% formic
      acid for phenolic acids and flavanols). From an analysis of the MS and UV data
      and in comparison with the authenticated standards, a total of 53 compounds were
      identified, including 33 anthocyanins, 12 flavonols, 4 phenolic acids, and 4
      flavanols/proanthocyanidins. With the method developed, a survey was then
      conducted to qualitatively assess the composition of polyphenols among 29
      different grape products including original grape, grape juice, grape wine, and
      grape-derived dietary supplements, and their chemical profiles were
      systematically compared. This method provided a comprehensive qualitative insight
      into the composition of polyphenols in grape-derived products.

PMID- 21879746
TI  - Synthesis of the 6-O-methyl-D-glycero-alpha-L-gluco-heptopyranose moiety present
      in the capsular polysaccharide from Campylobacter jejuni NCTC 11168.
AB  - The first synthesis of the 6-O-methyl-D-glycero-alpha-L-gluco-heptopyranose
      moiety present in the capsular polysaccharide from Campylobacter jejuni NCTC
      11168 is reported. The target (1) was synthesized as the 8-aminooctyl glycoside
      and then conjugated to bovine serum albumin (BSA) for the generation of
      antibodies recognizing this motif. Heptose 1 was obtained from D-galactose via a
      series of galactofuranose derivatives.

PMID- 21879747
TI  - Graphene growth using a solid carbon feedstock and hydrogen.
AB  - Graphene has been grown on Cu at elevated temperatures with different carbon
      sources (gaseous hydrocarbons and solids such as polymers); however the detailed
      chemistry occurring at the Cu surface is not yet known. Here, we explored the
      possibility of obtaining graphene using amorphous-carbon thin films, without and
      with hydrogen gas added. Graphene is formed only in the presence of H(2)(g),
      which strongly suggests that gaseous hydrocarbons and/or their intermediates are
      what yield graphene on Cu through the reaction of H(2)(g) and the amorphous
      carbon. The large area, uniform monolayer graphene obtained had electron and hole
      mobilities of 2520 and 2050 cm(2) V(-1) s(-1), respectively.

PMID- 21879749
TI  - Femtosecond nanofocusing with full optical waveform control.
AB  - The simultaneous nanometer spatial confinement and femtosecond temporal control
      of an optical excitation has been a long-standing challenge in optics. Previous
      approaches using surface plasmon polariton (SPP) resonant nanostructures or SPP
      waveguides have suffered from, for example, mode mismatch, or possible dependence
      on the phase of the driving laser field to achieve spatial localization. Here we
      take advantage of the intrinsic phase- and amplitude-independent nanofocusing
      ability of a conical noble metal tip with weak wavelength dependence over a broad
      bandwidth to achieve a 10 nm spatially and few-femtosecond temporally confined
      excitation. In combination with spectral pulse shaping and feedback on the second
      harmonic response of the tip apex, we demonstrate deterministic arbitrary optical
      waveform control. In addition, the high efficiency of the nanofocusing tip
      provided by the continuous micro- to nanoscale mode transformation opens the door
      for spectroscopy of elementary optical excitations in matter on their natural
      length and time scales and enables applications from ultrafast nano-opto
      electronics to single molecule quantum coherent control.

PMID- 21879748
TI  - [Ru(bpy)2(5-cyanouracil)2]2+ as a potential light-activated dual-action
      therapeutic agent.
AB  - The cation cis-[Ru(bpy)(2)(5CNU)(2)](2+) (bpy = 2,2'-bipyridine; 5CNU = 5
      cyanouracil) was synthesized and investigated for use as a potential light
      activated dual-action therapeutic agent. The complex undergoes efficient
      photoinduced 5CNU ligand exchange for solvent water molecules, thus
      simultaneously releasing biologically active 5CNU and generating
      [Ru(bpy)(2)(H(2)O)(2)](2+). The latter binds covalently to ds-DNA, such that
      photolysis results in the generation of 3 equiv of potential therapeutic agents
      from a single molecule.

PMID- 21879750
TI  - A 3500-year record of Hg and Pb contamination in a mediterranean sedimentary
      archive (the Pierre Blanche Lagoon, France).
AB  - A sediment core encompassing 3500 years of continuous sedimentation has been
      collected from a coastal lagoon located on the southwestern French Mediterranean
      coast. Lead concentrations and stable isotopes show that the sediments have
      recorded the three major periods of Pb pollution: the Etruscan-Greek-Roman period
      (650 BC to AD 50), the medieval period (AD 650 to AD 1450), and the modern period
      (from around AD 1850 to the present). These periods were separated by low
      pollution periods during the Dark Ages (between AD 50 and 650) and during the
      16th century. From the end of the 19th century to the 1960s, Pb pollution
      increased exponentially. Coal combustion was the major source of Pb in the lagoon
      in the second half of the 20th century. Both the decrease in coal consumption and
      the ban on leaded gasoline resulted in a decrease in Pb pollution by a factor of
      1.5 between 1973 and 1995. From 1991, sewage treatment plants and incinerators
      could be the major source of Pb. The average baseline Hg concentration from 1525
      BC to AD 900 was 0.017 +/- 0.003 MUg g-1 (n = 54). The Hg concentrations profile
      shows three major peaks: in AD 1150, AD 1660, and AD 1969, with the
      concentrations being respectively 8, 5, and 34 times higher than the baseline
      levels. The medieval peak (AD 1150) is attributed the medical use of Hg in the
      town of Montpellier and/or the burning of soil and vegetation. Noticeable Hg
      pollution was also detected during the 17th century in relation to gold and
      silver amalgamation in Europe. From the end of the 19th century, Hg
      concentrations increased exponentially until 1969. This modern pollution is
      attributed to the burning of coal.

PMID- 21879751
TI  - Novel synthesis of steryl esters from phytosterols and amino Acid.
AB  - The feasibility of esterification of phytosterol with the amino acid l-glutamic
      acid was established. The influence of various organic solvents was investigated,
      and n-butanol was selected as an ideal solvent for phytosteryl esters synthesis
      with l-glutamic acid. The reaction conditions were further optimized by
      orthogonal experiments, and a 92.3% degree of esterification was obtained when
      optimum conditions were used. FT-IR spectral, GC-MS, and NMR analyses were
      adopted to determine the steryl esters of l-glutamic acid. The FT-IR spectrum
      indicated the presence of ester bonds in the phytosteryl esters with l-glutamic
      acid, and on the basis of the detailed mass spectrography analysis, GC-MS and NMR
      offered an efficient and reliable way to confirm the steryl esters. This novel
      synthesis approach of phytosteryl esters with amino acid supplied a promising
      alternative to the substrate on esterification of phytosterols and thus can be
      readily applied to further studies of functional food ingredients of phytosteryl
      esters.

PMID- 21879753
TI  - Gate-activated photoresponse in a graphene p-n junction.
AB  - We study photodetection in graphene near a local electrostatic gate, which
      enables active control of the potential landscape and carrier polarity. We find
      that a strong photoresponse only appears when and where a p-n junction is formed,
      allowing on-off control of photodetection. Photocurrents generated near p-n
      junctions do not require biasing and can be realized using submicrometer gates.
      Locally modulated photoresponse enables a new range of applications for graphene
      based photodetectors including, for example, pixilated infrared imaging with
      control of response on subwavelength dimensions.

PMID- 21879754
TI  - Photochemical approach toward deposition of gold nanoparticles on functionalized
      carbon nanotubes.
AB  - The development of new methods for the facile synthesis of hybrid nanomaterials
      is of great importance due to their importance in nanotechnology. In this work,
      we report a new method to deposit Au nanoparticles on the surface of single
      walled carbon nanotubes (SWCNTs). Our approach consists of a one pot synthesis in
      which Au nanoparticles are generated in the presence of a photoreducing agent
      (Irgacure-2959) and carboxyl or polymer-functionalized SWCNTs (f-SWCNTs). We have
      observed that when carbon nanotubes are functionalized with polymers containing
      pendant amino groups, the latter can act as specific nucleation sites for well
      dispersed deposition of Au nanoparticles. The surface coverage of the Au
      nanoparticles can be observed by transmission electron spectroscopy. These
      observations are compared to that of carboxyl functionalized SWCNTs, in which
      less surface coverage was observed. The f-SWCNT/Au nanocomposites were also
      characterized by UV-vis, infrared, and Raman spectroscopy and thermogravimetric
      analysis (TGA). This facile and effective route can be implemented to deposit
      gold nanoparticles on other surface-functionalized carbon nanotubes.

PMID- 21879756
TI  - Uptake of Np(IV) by C-S-H phases and cement paste: an EXAFS study.
AB  - Nuclear waste disposal concepts developed worldwide foresee the use of
      cementitious materials for the immobilization of long-lived intermediate level
      waste (ILW). This waste form may contain significant amounts of neptunium-237,
      which is expected to be present as Np(IV) under the reducing conditions
      encountered after the closure of the repository. Predicting the release of Np(IV)
      from the cementitious near field of an ILW repository requires a sufficiently
      detailed understanding of its interaction with the main sorbing components of
      hardened cement paste (HCP). In this study, the uptake of Np(IV) by calcium
      silicate hydrates (C-S-H) and HCP has been investigated using extended X-ray
      absorption fine structure (EXAFS) spectroscopy. The EXAFS studies on Np(IV)-doped
      C-S-H and HCP samples reveal that Np(IV) is predominantly incorporated in the
      structure of C-S-H phases having different Ca:Si ratios. The two main species
      identified correspond to Np(IV) in C-S-H with a Ca:Si mol ratio of 1.65 as in
      fresh cement and with a Ca:Si mol ratio of 0.75 as in highly degraded cement. The
      local structure of Np(IV) changes with the Ca:Si mol ratio and does not depend on
      pH. Furthermore, Np(IV) shows the same coordination environment in C-S-H and HCP
      samples. This study shows that C-S-H phases are responsible for the Np(IV) uptake
      by cementitious materials and further that incorporation in the interlayer of the
      C-S-H structure is the dominant uptake mechanism.

PMID- 21879758
TI  - Facile charge-displacement at silicon gives spaced-out reaction.
AB  - Adsorbates on metals, but not previously on semiconductors, have been observed to
      display long-range repulsive interactions. On metals, due to efficient
      dissipation, the repulsions are weak, typically on the order of 5 meV at 10 A. On
      the 7*7 reconstruction of the Si(111) surface, charge transport through the
      surface has been demonstrated by others using charge injection by STM tips. Here
      we show that for both physisorbed brominated molecules, and for chemisorbed Br
      atoms, induced charge-transfer in the Si(111)-7*7 surface can lead to a strong
      repulsive interaction between adsorbates, calculated as 200 meV at 13.4 A. This
      large repulsive interaction must be channeled through the surface since it causes
      widely spaced "one-per-corner-hole" patterns of physisorption (three cases-
      directly observed here) and subsequent chemisorption (four cases observed). The
      patterns were observed by ultrahigh vacuum scanning tunneling microscopy for four
      different brominated hydrocarbon adsorbates; 1,2-dibromoethane, 1-bromopropane, 1
      bromopentane, and bromobenzene, deposited individually on the surface. In every
      case, adsorbates were overwhelmingly more likely to be found singly than multiply
      adjacent to a corner-hole, constituting a distinctive pattern having a
      probability p = 7 * 10(-5) compared to a random distribution.

PMID- 21879759
TI  - Excitation and tuning of higher-order Fano resonances in plasmonic oligomer
      clusters.
AB  - Plasmonic oligomer clusters are assemblies of closely packed metallic
      nanoparticles. They provide a rich set of spectral features such as Fano
      lineshapes and a simultaneous tunability of the supported resonances in the
      optical wavelength regime. In this study, we investigate numerically and
      experimentally clusters of plasmonic nanoparticles that exhibit multiple Fano
      resonances due to the interference of one broad superradiant mode and multiple
      narrow subradiant modes. In particular we investigate oligomers with multiple
      ring modes and elongated chains of nanoparticles surrounded by one ring of
      nanoparticles. We show that the number of nanoparticles and their respective
      arrangement in the cluster strongly influence the spectral position and
      modulation depth of the spectral signature of the supported modes. Our study
      opens up the pathway to "plasmonic super molecules" that show unprecedented
      tunability, which renders them highly suitable for applications such as
      multiwavelength surface-enhanced Raman scattering.

PMID- 21879757
TI  - Synthesis, biological, and antitumor activity of a highly potent 6-substituted
      pyrrolo[2,3-d]pyrimidine thienoyl antifolate inhibitor with proton-coupled folate
      transporter and folate receptor selectivity over the reduced folate carrier that
      inhibits beta-glycinamide ribonucleotide formyltransferase.
AB  - 2-Amino-4-oxo-6-substituted pyrrolo[2,3-d]pyrimidine antifolates with a thienoyl
      side chain (compounds 1-3, respectively) were synthesized for comparison with
      compound 4, the previous lead compound of this series. Conversion of hydroxyl
      acetylen-thiophene carboxylic esters to thiophenyl-alpha-bromomethylketones and
      condensation with 2,4-diamino-6-hydroxypyrimidine afforded the 6-substituted
      pyrrolo[2,3-d]pyrimidine compounds of type 18 and 19. Coupling with l-glutamate
      diethyl ester, followed by saponification, afforded 1-3. Compound 3 selectively
      inhibited the proliferation of cells expressing folate receptors (FRs) alpha or
      beta, or the proton-coupled folate transporter (PCFT), including KB and IGROV1
      human tumor cells, much more potently than 4. Compound 3 was more inhibitory than
      4 toward beta-glycinamide ribonucleotide formyltransferase (GARFTase). Both 3 and
      4 depleted cellular ATP pools. In SCID mice with IGROV1 tumors, 3 was more
      efficacious than 4. Collectively, our results show potent antitumor activity for
      3 in vitro and in vivo, associated with its selective membrane transport by FRs
      and PCFT over RFC and inhibition of GARFTase, clearly establishing the 3-atom
      bridge as superior to the 1-, 2-, and 4-atom bridge lengths for the activity of
      this series.

PMID- 21879760
TI  - Comprehensive profiling and quantitation of amine group containing metabolites.
AB  - Primary and secondary amines, including amino acids, biogenic amines, hormones,
      neurotransmitters, and plant siderophores, are readily derivatized with 6
      aminoquinolyl-N-hydroxysuccinimidyl carbamate using easily performed experimental
      methodology. Complex mixtures of these amine derivatives can be fractionated and
      quantified using liquid chromatography-electrospray ionization-mass spectrometry
      (LC-ESI-MS). Upon collision induced dissociation (CID) in a quadrupole collision
      cell, all derivatized compounds lose the aminoquinoline tag. With the use of
      untargeted fragmentation scan functions, such as precursor ion scanning, the loss
      of the aminoquinoline tag (Amq) can be monitored to identify derivatized species;
      and the use of targeted fragmentation scans, such as multiple reaction
      monitoring, can be exploited to quantitate amine-containing molecules. Further,
      with the use of accurate mass, charge state, and retention time, identification
      of unknown amines is facilitated. The stability of derivatized amines was found
      to be variable with oxidatively labile derivatives rapidly degrading. With the
      inclusion of antioxidant and reducing agents, tris(2-carboxyethyl)-phosphine
      (TCEP) and ascorbic acid, into both extraction solvents and reaction buffers,
      degradation was significantly decreased, allowing reproducible identification and
      quantification of amine compounds in large sample sets.

PMID- 21879761
TI  - Threshold-avoiding proteomics pipeline.
AB  - We present a new proteomics analysis pipeline focused on maximizing the dynamic
      range of detected molecules in liquid chromatography-mass spectrometry (LC-MS)
      data and accurately quantifying low-abundance peaks to identify those with
      biological relevance. Although there has been much work to improve the quality of
      data derived from LC-MS instruments, the goal of this study was to extend the
      dynamic range of analyzed compounds by making full use of the information
      available within each data set and across multiple related chromatograms in an
      experiment. Our aim was to distinguish low-abundance signal peaks from noise by
      noting their coherent behavior across multiple data sets, and central to this is
      the need to delay the culling of noise peaks until the final peak-matching stage
      of the pipeline, when peaks from a single sample appear in the context of all
      others. The application of thresholds that might discard signal peaks early is
      thereby avoided, hence the name TAPP: threshold-avoiding proteomics pipeline.
      TAPP focuses on quantitative low-level processing of raw LC-MS data and includes
      novel preprocessing, peak detection, time alignment, and cluster-based matching.
      We demonstrate the performance of TAPP on biologically relevant sample data
      consisting of porcine cerebrospinal fluid spiked over a wide range of
      concentrations with horse heart cytochrome c.

PMID- 21879762
TI  - Odd-even effect of repeating aminoethylene units in the side chain of N
      substituted polyaspartamides on gene transfection profiles.
AB  - A series of the N-substituted polyaspartamides possessing repeating aminoethylene
      units in the side chain was prepared in this study to identify polyplexes with
      effective endosomal escape and low cytotoxicity. All cationic N-substituted
      polyaspartamides showed appreciably lower cytotoxicity than that of commercial
      transfection reagents. Interestingly, a distinctive odd-even effect of the
      repeating aminoethylene units in the polymer side chain on the efficiencies of
      endosomal escape and transfection to several cell lines was observed. The
      polyplexes from the polymers with an even number of repeating aminoethylene units
      (PA-Es) achieved an order of magnitude higher transfection efficiency, without
      marked cytotoxicity, than those of the polymers with an odd number of repeating
      aminoethylene units (PA-Os). This odd-even effect agreed well with the buffering
      capacity of these polymers as well as their capability to disrupt membrane
      integrity selectively at endosomal pH, leading to highly effective endosomal
      escape of the PA-E polyplexes. Furthermore, the formation of a polyvalent charged
      array with precise spacing between protonated amino groups in the polymer side
      chain was shown to be essential for effective disruption of the endosomal
      membrane, thus facilitating transport of the polyplex into the cytoplasm. These
      data provide useful knowledge for designing polycations to construct safe and
      efficient nonviral gene carriers.

PMID- 21879763
TI  - Adsorption, desorption, and removal of polymeric nanomedicine on and from
      cellulose surfaces: effect of size.
AB  - The increased production and commercial use of nanoparticulate drug delivery
      systems combined with a lack of regulation to govern their disposal may result in
      their introduction to soils and ultimately into groundwater systems. To better
      understand how such particles interact with environmentally significant
      interfaces, we study the adsorption, desorption, and removal behavior of
      poly(ethylene glycol)-based nanoparticulate drug delivery systems on and from
      cellulose, which is the most common organic compound on Earth. It is shown that
      such an adsorption process is only partially reversible, and most of the
      adsorbate particles do not desorb from the cellulose surface even upon rinsing
      with a large amount of water. The rate constant of adsorption decreases with
      increasing particle size. Furthermore, hydrodynamic forces acting parallel to the
      surfaces are found to be of great importance in the context of particle dynamics
      near the cellulose surface, and ultimately responsible for the removal of some
      fraction of particles via rolling or sliding. As the particle size increases, the
      removal rates of the particles increase for a given hydrodynamical condition.

PMID- 21879764
TI  - Peptide mixtures can self-assemble into large amyloid fibers of varying size and
      morphology.
AB  - Peptide mixtures spontaneously formed micrometer-sized fibers and ribbons from
      aqueous solution. Hydrolyzed gliadin produced short, slightly elliptical fibers
      while hydrolyzed wheat gluten, a mixture of gliadin and glutenin, formed round
      fibers of similar size. Mixing hydrolyzed gliadin with increasing molar amounts
      of myoglobin or amylase resulted in longer, wider fibers that transitioned from
      round to rectangular cross section. Fiber size, morphology, and modulus were
      controlled by peptide mixture composition. Fourier transform infrared (FT-IR)
      spectroscopy results showed that peptides experienced alpha to beta transitions
      forming an elementary cross-beta peptide secondary structure, indicative of
      amyloids. Large fiber formation was observed to be dependent on hydrophobic
      packing between constituent peptides. A model was developed to show how the fiber
      morphology was influenced by the peptides in the mixture.

PMID- 21879765
TI  - Cytokinin-dependent improvement in transgenic P(SARK)::IPT tobacco under nitrogen
      deficiency.
AB  - Wild-type (WT) and transgenic tobacco plants overexpressing
      isopentenyltransferase (IPT), a gene coding the rate-limiting step in cytokinin
      (CKs) synthesis, were grown under limited nitrogen (N) conditions to evaluate the
      role of CKs in NUE (N-use efficiency) and in different parameters that determine
      the quality of tobacco leaves. The results indicate that WT tobacco plants
      submitted to N deficiency show a decline in the leaf/root ratio, associated with
      a decrease in the NUE and in tobacco-leaf quality, defined by an increase in the
      quantity of nicotine. On the contrary, the transgenic plants submitted to N
      deficiency maintained the leaf/root ratio, presenting a higher NUE and greater
      quality of tobacco leaves than the WT plants, as the latter showed reduced
      nicotine and an increase in reducing sugars under severe N-deficiency conditions.
      Therefore, the overexpression of CKs under N deficiency could be a useful tool to
      improve tobacco cultivation, given that it could reduce N-fertilizer application
      and thereby provide economic savings and environmental benefits, maintaining
      yield and improving tobacco leaf quality.

PMID- 21879766
TI  - Comparison of odor-active compounds in grapes and wines from vitis vinifera and
      non-foxy American grape species.
AB  - Native American grape (Vitis) species have many desirable properties for
      winegrape breeding, but hybrids of these non-vinifera wild grapes with  Vitis
      vinifera  often have undesirable aromas. Other than the foxy-smelling compounds
      in  Vitis labrusca  and  Vitis rotundifolia , the aromas inherent to American
      Vitis species are not well characterized. In this paper, the key odorants in wine
      produced from the American grape species  Vitis riparia  and  Vitis cinerea  were
      characterized in comparison to wine produced from European winegrapes (V.
      vinifera). Volatile compounds were extracted by solid-phase microextraction
      (SPME) and identified by gas chromatography-olfactometry/mass spectrometry (GC
      O/MS). On the basis of flavor dilution values, most grape-derived compounds with
      fruity and floral aromas were at similar potency, but non-vinifera wines had
      higher concentrations of odorants with vegetative and earthy aromas: eugenol, cis
      3-hexenol, 1,8-cineole, 3-isobutyl-2-methoxypyrazine (IBMP), and 3-isopropyl-2
      methoxypyrazine (IPMP). Elevated concentrations of these compounds in non
      vinifera wines were confirmed by quantitative GC-MS. Concentrations of IBMP and
      IPMP were well above sensory threshold in both non-vinifera wines. In a follow-up
      study, IBMP and IPMP were surveyed in 31 accessions of V. riparia, V. rupestris,
      and V. cinerea. Some accessions had concentrations of >350 pg/g IBMP or >30 pg/g
      IPMP, well above concentrations reported in previous studies of harvest-ripe
      vinifera grapes. Methyl anthranilate and 2-aminoacetophenone, key odorants
      responsible for the foxiness of V. labrusca grapes, were undetectable in both the
      V. riparia and V. cinerea wines (<10 MUg/L).

PMID- 21879767
TI  - Formation pathway of CuInSe2 nanocrystals for solar cells.
AB  - Copper, indium, and gallium chalcogenide nanocrystals (binary, ternary, and
      quaternary) have been used to fabricate high-efficiency thin-film solar cells.
      These solution-based methods are being scaled-up and may serve as the basis for
      the next generation of low-cost solar cells. However, the formation pathway to
      reach stoichiometric ternary CuInSe(2) or any chalcopyrite phase ternary or
      quaternary nanocrystal in the system has not been investigated but may be of
      significant importance to improving nanocrystal growth and discovering new
      methods of synthesis. Here, we present the results of X-ray diffraction, electron
      microscopy, compositional analysis, IR absorption, and mass spectrometry that
      reveal insights into the formation pathway of CuInSe(2) nanocrystals. Starting
      with CuCl, InCl(3), and elemental Se all dissolved in oleylamine, the overall
      reaction that yields CuInSe(2) involves the chlorination of the hydrocarbon
      groups of the solvent. Further, we show that the amine and alkene functional
      groups in oleylamine are not necessary for the formation of CuInSe(2)
      nanocrystals by conducting successful syntheses in 1-octadecene and octadecane.
      Hence, the role of oleylamine is not limited to nanocrystal size and morphology
      control; it also acts as a reactant in the formation pathway. Typically, the
      formation of copper selenide (CuSe) and indium selenide (InSe) nanocrystals
      precedes the formation of CuInSe(2) nanocrystals in oleylamine. But it was also
      found that Cu(2-x)Se (0 < x < 0.5) and In(2)Se(3) were the primary intermediates
      involved in the formation of CISe in a purely non-coordinating solvent such as 1
      octadecene, which points to the surface-stabilization effect of the coordinating
      solvent on the less thermodynamically stable indium selenide (InSe) nanocrystals.
      We also show that the yield of the chalcopyrite phase of CuInSe(2) (as opposed to
      the sphalerite phase) can be increased by reacting CuSe nanocrystals with
      InCl(3).

PMID- 21879768
TI  - Serum levels of pregnancy zone protein are elevated in presymptomatic Alzheimer's
      disease.
AB  - We have sought for disease-related proteins that could predict the onset of
      Alzheimer's disease (AD) in a study population derived from the Rotterdam Scan
      Study, a population-based prospective cohort study designed to investigate the
      etiology and natural history of age-related brain changes in the elderly. The
      serum proteome of 43 persons who developed AD, after an average of 4.2 years (+/
      2.6 years SD) after blood sampling, and 43 gender- and age-matched controls who
      remained dementia-free during follow-up was investigated by liquid chromatography
      mass spectrometry. We identified 61 differentially expressed peptides between
      presymptomatic AD and controls, 9 of which were derived from pregnancy zone
      protein (PZP). Quantitative measurements using a multiple reaction monitoring
      assay showed a significant increase in concentration of PZP in presymptomatic AD
      (34.3 +/- 20.6 mg/L) compared with controls (23.6 +/- 13.6 mg/L) (p = 0.006). The
      difference in PZP was significant in women. Immunohistochemical validation of the
      findings on brain tissue sections showed strong PZP expression in senile plaques
      and in microglial and glial cells in AD with only low expression in some
      scattered glial cells in controls.

PMID- 21879769
TI  - Characterization of lignin structures and lignin-carbohydrate complex (LCC)
      linkages by quantitative 13C and 2D HSQC NMR spectroscopy.
AB  - To characterize the lignin structures and lignin-carbohydrate complex (LCC)
      linkages, milled wood lignin (MWL) and mild acidolysis lignin (MAL) with a high
      content of associated carbohydrates were sequentially isolated from ball-milled
      poplar wood. Quantification of their structural features has been achieved by
      using a combination of quantitative (13)C and 2D HSQC NMR techniques. The results
      showed that acetylated 4-O-methylgluconoxylan is the main carbohydrate associated
      with lignins, and acetyl groups frequently acylate the C2 and C3 positions. MWL
      and MAL exhibited similar structural features. The main substructures were beta-O
      4' aryl ether, resinol, and phenylcoumaran, and their abundances per 100 Ar units
      changed from 41.5 to 43.3, from 14.6 to 12.7, and from 3.7 to 4.0, respectively.
      The S/G ratios were estimated to be 1.57 and 1.62 for MWL and MAL, respectively.
      Phenyl glycoside and benzyl ether LCC linkages were clearly quantified, whereas
      the amount of gamma-ester LCC linkages was ambiguous for quantification.

PMID- 21879770
TI  - Atmospheric chemistry of (Z)-CF3CH?CHCF3: OH radical reaction rate coefficient
      and global warming potential.
AB  - Rate coefficients, k, for the gas-phase reaction of the OH radical with (Z)
      CF(3)CH?CHCF(3) (cis-1,1,1,4,4,4-hexafluoro-2-butene) were measured under pseudo
      first-order conditions in OH using pulsed laser photolysis (PLP) to produce OH
      and laser-induced fluorescence (LIF) to detect it. Rate coefficients were
      measured over a range of temperatures (212-374 K) and bath gas pressures (20-200
      Torr; He, N(2)) and found to be independent of pressure over this range of
      conditions. The rate coefficient has a non-Arrhenius behavior that is well
      described by the expression k(1)(T) = (5.73 +/- 0.60) * 10(-19) * T(2) * exp[(678
      +/- 10)/T] cm(3) molecule(-1) s(-1) where k(1)(296 K) was measured to be (4.91 +/
      0.50) * 10(-13) cm(3) molecule(-1) s(-1) and the uncertainties are at the 2sigma
      level and include estimated systematic errors. Rate coefficients for the
      analogous OD radical reaction were determined over a range of temperatures (262
      374 K) at 100 Torr (He) to be k(2)(T) = (4.81 +/- 0.20) * 10(-19) * T(2) *
      exp[(776 +/- 15)/T], with k(2)(296 K) = (5.73 +/- 0.50) * 10(-13) cm(3) molecule(
      1) s(-1). OH radical rate coefficients were also measured at 296, 345, and 375 K
      using a relative rate technique and found to be in good agreement with the PLP
      LIF results. A room-temperature rate coefficient for the O(3) + (Z)
      CF(3)CH?CHCF(3) reaction was measured using an absolute method with O(3) in
      excess to be <6 * 10(-21) cm(3) molecule(-1) s(-1). The atmospheric lifetime of
      (Z)-CF(3)CH?CHCF(3) due to loss by OH reaction was estimated to be ~20 days.
      Infrared absorption spectra of (Z)-CF(3)CH?CHCF(3) measured in this work were
      used to determine a (Z)-CF(3)CH?CHCF(3) global warming potential (GWP) of ~9 for
      the 100 year time horizon. A comparison of the OH reactivity of (Z)
      CF(3)CH?CHCF(3) with other unsaturated fluorinated compounds is presented.

PMID- 21879771
TI  - The "hockey sticks" effect revisited: the conformational and electronic
      properties of 3,7-dithia-1,5-diazabicyclo[3.3.1]nonane from the QTAIM
      perspective.
AB  - The conformational effects in bicyclo[3.3.1]nonanes, while thoroughly studied,
      have not yet received the full theoretical explanation. R. F. W. Bader's quantum
      theory of atoms in molecules presents unique opportunities for studying the
      stereoelectronic interactions (SEI) and weak intramolecular bonding leading to
      these effects. Here, we report the study of 3,7-dithia-1,5
      diazabicyclo[3.3.1]nonane by means of the topological analysis of the calculated
      (MP2(full)/6-311++G**) and experimental (X-ray derived) charge density to reveal
      the origins of the so-called "hockey sticks" effect observed in similar
      compounds. A new explanation of the relative stability of bicyclo[3.3.1]nonane
      conformers based on the analysis of the QTAIM atomic energies is given. The H...H
      and S...S interactions in bicyclo[3.3.1]nonane and its dithia derivatives are
      shown to be significant factors contributing to the differences in the relative
      stability of the conformers.

PMID- 21879772
TI  - Interaction of alcohols with 2-fluoro- and 4-fluorophenylacetylenes: infrared
      optical double resonance spectroscopic and computational investigation.
AB  - Alcohol complexes of 4-fluorophenylacetylene and 2-fluorophenylacetylene were
      investigated using IR-UV double resonance spectroscopy. Methanol forms a cyclic
      complex with both the fluorophenylacetylenes incorporating C-H...O and O-H...pi
      hydrogen bonds, the structure of which is similar to that of the corresponding
      water complex but different from that of a phenylacetylene-methanol complex. The
      anti conformer of ethanol also binds in a similar fashion to both the
      fluorophenylacetylenes. Additionally, the gauche conformer of ethanol binds to 2
      fluorophenylacetylene in a distinctly different structural motif that
      incorporates C-H...F and O-H...pi hydrogen bonds. The OH group of
      trifluoroethanol interacts primarily with the pi electron density of the C=C
      bond. The pi electron density of the C=C bond is the principal point of
      interaction between the alcohols and both the fluorophenylacetylenes. The present
      results are indicative of the fact that fluorine substitution on the phenyl ring
      is sufficient to eliminate the subtle hydrogen bonding behavior of
      phenylacetylene.

PMID- 21879773
TI  - Surface-induced self-assembly of dipeptides onto nanotextured surfaces.
AB  - There is an increasing interest for the utilization of biomolecules for
      fabricating novel nanostructures due to their ability for specific molecular
      recognition, biocompatibility, and ease of availability. Among these molecules,
      diphenylalanine (Phe-Phe) dipeptide is considered as one of the simplest
      molecules that can generate a family of self-assembly based nanostructures. The
      properties of the substrate surface, on which the self-assembly process of these
      peptides occurs, play a critical role. Herein, we demonstrated the influence of
      surface texture and functionality on the self-assembly of Phe-Phe dipeptides
      using smooth silicon surfaces, anodized aluminum oxide (AAO) membranes, and
      poly(chloro-p-xylylene) (PPX) films having columnar and helical morphologies. We
      found that helical PPX films, AAO, and silicon surfaces induce similar self
      assembly processes and the surface hydrophobicity has a direct influence for the
      final dipeptide structure whether being in an aggregated tubular form or creating
      a thin film that covers the substrate surface. Moreover, the dye staining data
      indicates that the surface charge properties and hence the mechanism of the self
      assembly process are different for tubular structures as opposed to the peptidic
      film. We believe that our results may contribute to the control of surface
      induced self-assembly of peptide molecules and this control can potentially allow
      the fabrication of novel peptide based materials with desired morphologies and
      unique functionalities for different technological applications.

PMID- 21879774
TI  - A three-component reaction forming naphthyridones--synthesis of lophocladine
      analogs.
AB  - A three-component reaction forming dihydro 2,7-naphthyridine-1-ones has been
      developed. These unstable dihydro intermediates can be either oxidized or reduced
      to form naphthyridones or tetrahydro naphthyridones, respectively. The reaction
      tolerates a large variety of aldehydes and amines, and the produced compounds are
      analogs of the natural product lophocladine A.

PMID- 21879775
TI  - Off-label pharmacovigilance.

PMID- 21879776
TI  - Is the large simple trial design used for comparative, post-approval safety
      research? A review of a clinical trials registry and the published literature.
AB  - Post-approval, observational drug safety studies face well known difficulties in
      controlling for confounding, particularly confounding by indication for drug use.
      A study design that addresses confounding by indication is the large simple trial
      (LST). LSTs are characterized by large sample sizes, often in the thousands;
      broad entry criteria consistent with the approved medication label; randomization
      based on equipoise, i.e. neither physician nor patient believes that one
      treatment option is superior; minimal, streamlined data collection requirements;
      objectively-measured endpoints (e.g. death, hospitalization); and follow-up that
      minimizes interventions or interference with normal clinical practice. In theory
      then, the LST is a preferred study design for drug and vaccine safety research
      because it controls for biases inherent to observational research while still
      providing results that are generalizable to 'real-world' use. To evaluate whether
      LSTs are used for comparative safety evaluation and if the design is, in fact,
      advantageous compared with other designs, we conducted a review of the published
      literature (1949 through 31 December 2010) and the ClinicalTrials.gov registry
      (2000 through 31 December 2010). Thirteen ongoing or completed safety LSTs were
      identified. The design has rarely been used in comparative drug safety research,
      which is due to the operational, financial and scientific hurdles of implementing
      the design. The studies that have been completed addressed important clinical
      questions and, in some cases, led to re-evaluation of medical practice. We
      conclude the design has demonstrated utility for comparative safety research of
      medicines and vaccines if the necessary scientific and operational conditions for
      its use are met.

PMID- 21879778
TI  - Fluoroquinolone-associated myasthenia gravis exacerbation: evaluation of
      postmarketing reports from the US FDA adverse event reporting system and a
      literature review.
AB  - BACKGROUND: Exacerbations of myasthenia gravis have been reported in
      antibacterial-treated patients. In animal and in vitro models of experimentally
      induced myasthenia gravis, fluoroquinolones exhibit neuromuscular blockade.
      OBJECTIVE: The aim of this retrospective study was to evaluate postmarketing
      adverse event reports submitted to the US FDA and case reports published in the
      scientific literature for a potential association between fluoroquinolone
      exposure and acute exacerbations of myasthenia gravis. METHODS: On 1 March 2011,
      we searched the FDA Adverse Event Reporting System (AERS) database to retrieve
      all reports of myasthenia gravis exacerbation as a serious adverse event in
      patients treated with fluoroquinolones. We also conducted an Internet-based
      search using EMBASE for additional English-language cases in the scientific
      literature. RESULTS: We identified a total of 37 unique cases describing
      myasthenia gravis exacerbation following fluoroquinolone systemic exposure. We
      retrieved AERS reports for 27 non-ventilated patients administered the following
      fluoroquinolones: levofloxacin (n = 9), moxifloxacin (n = 6), ciprofloxacin (n =
      6), ofloxacin (n = 2), gatifloxacin (n = 2), norfloxacin (n = 1) and
      trovafloxacin (n = 1). Additionally, we retrieved ten case reports published in
      the literature involving non-ventilated patients administered ciprofloxacin (n =
      4), levofloxacin (n = 2) and ofloxacin, norfloxacin, pefloxacin and prulifloxacin
      (1 patient each). Myasthenia gravis exacerbations developed a median of 1 day
      following fluoroquinolone exposure. The 37 cases describe dyspnoea (n = 19; 51%),
      myasthenic crisis requiring ventilatory support (n = 11; 30%) and death (n = 2;
      5%). Additional exacerbation-related adverse events were generalized muscle
      weakness (n = 20; 54%), dysphagia (n = 9; 24%), diplopia (n = 6; 16%) and ptosis
      (n = 6; 16%). Six patients (16%) experienced a positive rechallenge, with
      recurrent myasthenia gravis exacerbation after fluoroquinolone reintroduction.
      CONCLUSIONS: Fluoroquinolone exposure may result in potentially life-threatening
      myasthenia gravis exacerbations in patients with underlying disease. Healthcare
      professionals should be aware of this serious drug-disease association and
      carefully weigh the benefit-risks of fluoroquinolones when treating infections in
      non-ventilated myasthenic patients.

PMID- 21879780
TI  - The case-population study design: an analysis of its application in
      pharmacovigilance.
AB  - BACKGROUND: The case-population approach or population-based case-cohort approach
      is derived from the case-control design and consists of comparing past exposure
      to a given risk factor in subjects presenting a given disease or symptom (cases)
      with the exposure rate to this factor in the whole cohort or in the source
      population of cases. In the same way as the case-control approach, the case
      population approach measures the disproportionality of exposure between cases of
      a given disease and their source population expressed in the form of an odds
      ratio approximating the ratio of the risks in exposed and not-exposed populations
      (relative risk). OBJECTIVE: The aim of this study was to (i) present the case
      population principle design in a way understandable for non-statisticians; (ii)
      propose the easiest way of using it for pharmacovigilance purposes (mainly
      alerting and hypothesis testing); (iii) propose simple formulae for computing an
      odds ratio and its confidence interval; (iv) apply the approach to several
      practical and published examples; and (v) discuss its pros and cons in the
      context of real life. METHODS: The approach used is derived from that comparing
      two rates expressed as person-time denominators. It allows easy computation of an
      odds ratio and its confidence interval under several hypotheses. Results obtained
      with the case-population approach were compared with those of case-control
      studies published in the literature. RESULTS: Relevance and limits of the
      proposed approach are illustrated by examples taken from published
      pharmacoepidemiological studies. The odds ratio (OR) reported in a European case
      control study on centrally acting appetite suppressants and primary pulmonary
      hypertension was 23.1 (95% CI 6.9, 77.7) versus 31 (95% CI 16.2, 59.2) using the
      case-population approach. In the European case-control studies SCAR (Severe
      Cutaneous Adverse Reactions) and EuroSCAR on the risk of toxic epidermal
      necrolysis associated with the use of medicines, the OR for cotrimoxazole was 160
      and 102, respectively, versus 44.4 using the case-population approach. Similarly,
      these two case-control studies found ORs of 12 and 72 for carbamazepine versus
      24.4 using the case-population approach, 8.7 and 16 for phenobarbital versus
      21.9, 12 for piroxicam (analysed in the SCAR study only) versus 14.5, and 5.5 and
      18 for allopurinol versus 3.4 using the case-population approach. CONCLUSIONS:
      Being based on the estimate derived from sales statistics of the total exposure
      time in the source population of cases, the method can be used even when there is
      no information about the actual number of exposed subjects in this population.
      Although the case-population approach suffers from limitations stemming from its
      main advantage, i.e. impossibility to control possible confounders and to
      quantify the strength of associations due to the absence of an ad hoc control
      group, it is particularly useful to use in routine practice, mainly for purposes
      of signal generation and hypothesis testing in drug surveillance.

PMID- 21879779
TI  - Drug-induced taste and smell alterations: a case/non-case evaluation of an
      italian database of spontaneous adverse drug reaction reporting.
AB  - BACKGROUND: The frequency and clinical features of drug-related taste and/or
      smell impairments are currently unclear. OBJECTIVE: The aim of this study was to
      identify major drug classes associated with taste and smell alterations reported
      to the Italian spontaneous adverse drug reaction (ADR) reporting database.
      METHODS: The association between drug and altered taste or smell was investigated
      by case/non-case methodology. The reporting odds ratio (ROR) was used as a
      measure of disproportionality. Cases were defined as patients with at least one
      ADR related to taste or smell impairments. The non-cases included all patients
      without any ADRs related to taste or smell alterations. RESULTS: According to the
      selection criteria, 52 166 reports were included in the analysis. Overall, 182
      cases of drug-related taste and/or smell dysfunctions were identified.
      Statistically significant unadjusted RORs were reported for macrolides (n = 31;
      7.1; 95% CI 4.8, 10.5), terbinafine (the only drug reported within the group of
      antimycotics belonging to the Anatomical Therapeutic Chemical class D01AE) [n =
      17; 76.4; 95% CI 44.0, 132.6], fluoroquinolones (n = 15; 1.7; 95% CI 1.0, 2.8)
      and protein kinase inhibitors (n = 10; 4.0; 95% CI 2.1, 7.7). When RORs were
      adjusted for sex and age category, the disproportion remained statistically
      significant for all of the previously mentioned drug classes. CONCLUSIONS: Taste
      and/or smell abnormalities are common, sometimes unexpected and often persistent
      complaints of patients during pharmacological treatments. Physicians should be
      aware of the impact of these ADRs on patients' quality of life.

PMID- 21879777
TI  - Drug-induced photosensitivity: culprit drugs, management and prevention.
AB  - Photo-induced drug eruptions are cutaneous adverse events due to exposure to a
      drug and either ultraviolet or visible radiation. Based on their pathogenesis,
      they can be classified as phototoxic or photoallergic drug eruptions, although in
      many cases it is not possible to determine whether a particular eruption is due
      to a phototoxic or photoallergic mechanism. In this review, the diagnosis,
      prevention and management of drug-induced photosensitivity are discussed.
      Diagnosis is based primarily on the history of drug intake and the clinical
      appearance of the eruption, primarily affecting sun-exposed areas of the skin.
      Phototesting and photopatch testing can be useful adjuncts in making a diagnosis.
      The mainstay of management is prevention, including informing patients of the
      possibility of increased sun sensitivity and the use of sun protective measures.
      However, once the eruption has occurred, it may be necessary to discontinue the
      culprit medication and treat the eruption with a potent topical corticosteroid.
      Drugs that have been implicated in causing photosensitive eruptions are reviewed.
      Tetracycline, doxycycline, nalidixic acid, voriconazole, amiodarone,
      hydrochlorothiazide, naproxen, piroxicam, chlorpromazine and thioridazine are
      among the most commonly implicated medications. We review the medical literature
      regarding evidence for the culpability of each drug, including the results of
      phototesting, photopatch testing and rechallenge testing.

PMID- 21879781
TI  - Effect of pre-medication on early adverse reactions following antivenom use in
      snakebite: a systematic review and meta-analysis.
AB  - BACKGROUND: Pre-medication has been used to protect against early adverse
      reactions (EAR) following antivenom administration after snakebite. Studies have
      evaluated its efficacy with variable results. OBJECTIVE: The aim of the study was
      to conduct a systematic review and meta-analysis of published data to assess the
      effect of pre-medication on the risk of EAR. METHODS: We conducted a search of
      MEDLINE, the Cochrane Database and various search engines/websites, searched
      handbooks, book chapters and peer-reviewed articles relating to clinical
      snakebite, and consulted experts in this field. The search was on published
      literature up to September 2010. A meta-analysis was conducted of all randomized
      and non-randomized studies of EAR following antivenom in snakebite that utilized
      either adrenaline (epinephrine)-containing or non-adrenaline (antihistamines,
      corticosteroids)-containing pre-medications compared with control groups. We
      performed either random- or fixed-effects analysis based on the presence of
      heterogeneity as assessed with two tests, including the I2 statistic, and
      performed restricted analyses on data derived from randomized or non-randomized
      studies. Sensitivity analysis investigating the influence of single studies on
      overall estimates was conducted and we determined publication bias where detected
      in both of the two tests used for its assessment. RESULTS: Three randomized and
      four non-randomized studies were selected for inclusion in this study. When all
      ten comparisons from the seven selected studies were combined (with a total of
      434 subjects in the pre-medication groups and 399 subjects in the control
      groups), the overall summary risk ratio (RR) for EAR was 0.70 (95% CI 0.50, 0.99;
      p = 0.041; I 2= 66.5%). When analysis was restricted to only studies employing
      adrenaline-containing pre-medication, the combined summary RR was 0.32 (95% CI
      0.18, 0.58; p < 0.0001; I2 = 9.5%). Results were not statistically significant
      when analyses were restricted to studies employing non-adrenaline-containing pre
      medications, or cohort or randomized controlled designs. Analysis was limited by
      heterogeneity, paucity and quality of data. CONCLUSIONS: Findings are consistent
      with a substantial beneficial effect of adrenaline pre-medication, but a marginal
      benefit with the combination of pre-medications used against EAR could not be
      excluded. Future studies are recommended and they should explore possible
      synergism of broader combinations of drugs and effects of mode of antivenom
      administration in large randomized controlled trials. Meanwhile, highly purified
      antivenoms with less risk of EAR should be made available in the rural tropics.

PMID- 21879782
TI  - Communication in drug safety: a report from an interactive debate held at the
      10th annual meeting of the international society of pharmacovigilance (ISoP),
      2010.

PMID- 21879784
TI  - Viral hepatitis A, active component, U.S. Armed Forces, 2000-2010.
AB  - From 2000 to 2010, there were 214 incident diagnoses of acute hepatitis A among
      active component members of the U.S. Armed Forces; the crude overall incidence
      rate during the period was 1.37 per 100,000 person-years. Rates of incident
      diagnoses of acute hepatitis A were relatively low throughout the period and much
      lower than during the pre-vaccine era (1990-1996). There were disproportionate
      numbers of diagnoses of acute hepatitis A among service members born in countries
      endemic for the infection. The low rates of acute hepatitis A among U.S. military
      members overall reflect the widespread use of hepatitis A virus vaccine.

PMID- 21879785
TI  - Viral hepatitis B, active component, U.S. Armed Forces, 2000-2010.
AB  - From 2000 to 2010, there were 903 and 1,484 incident diagnoses of acute and
      chronic hepatitis B virus infections, respectively, among active component
      members of the U.S. Armed Forces; crude overall incidence rates during the period
      were 5.8 (acute hepatitis B) and 9.5 (chronic hepatitis B) per 100,000 person
      years. Incidence rates of both acute and chronic hepatitis B declined during the
      period. There were relatively high crude rates of hepatitis B diagnoses among
      service members who were Asian/Pacific Islanders, females, health care workers,
      and older than 40 years. Declining rates of hepatitis B diagnoses in the U.S.
      military likely reflect increased avoidance of risky behaviors, vaccination of
      immunologically naive recruits, and accession into service of increasing numbers
      of individuals immunized during childhood.

PMID- 21879786
TI  - Viral hepatitis C, active component, U.S. Armed Forces, 2000-2010.
AB  - From 2000 to 2010, there were 808 and 2,738 incident cases of acute and chronic
      hepatitis C, respectively, among active component members of the U.S. Armed
      Forces; crude overall incidence rates during the period were 5.16 (acute
      hepatitis C) and 17.48 (chronic hepatitis C) per 100,000 person-years. Incidence
      rates of acute hepatitis C diagnoses steadily declined (by approximately 80
      percent overall) during the period; rates of chronic hepatitis C diagnoses also
      declined but proportionately less overall than for acute hepatitis C. Declining
      trends likely reflect avoidance of risky behaviors, comprehensive screening of
      blood products, and accession standards that include screening for illicit drugs
      and antibodies to HIV-1.

PMID- 21879787
TI  - Updates: Routine screening for antibodies to HIV-1, civilian applicants for U.S.
      military service and U.S. Armed Forces, active and reserve components.
AB  - During routine testing of civilian applicants for U.S. military service, the
      overall seroprevalence of antibodies to HIV-1 was lower in 2010 than in any year
      since 1990. Among members of the active components of the U.S. Army and Air
      Force, HIV-1 seroprevalences were higher in 2008-2010 than in recent prior years.
      Among members of the active components of the U.S. Navy and Marine Corps, the
      Marine Corps Reserve, and the Army National Guard, HIV-1 seroprevalences have
      slightly declined or remained relatively stable for at least ten years. In the
      reserve components of most of the service branches, it is difficult to discern
      long-term trends because of instability of seroprevalences observed in the
      relatively small numbers of reserve component members tested each year.

PMID- 21879788
TI  - Surveillance snapshot: service members with hepatitis B, hepatitis C, and HIV-1,
      active component, U.S. Armed Forces.
AB  - Risk factors and routes of transmission of hepatitis B virus (HBV), hepatitis C
      virus (HCV), and human immunodeficiency virus (HIV) are similar; therefore,
      individuals infected with one of these viruses may be coinfected or at high risk
      of acquiring another infection. Among active component service members diagnosed
      with HBV infections (n=2,204) between 2000 and 2010, 86 (3.9%) were also
      diagnosed with HCV and 49 (2.2%) with HIV-1. Among service members diagnosed with
      HCV infections (n=3,185) between 2000 and 2010, 86 (2.7%) were diagnosed with HBV
      and 45 (1.4%) with HIV-1. Four service members were diagnosed with HBV, HCV, and
      HIV-1 during the period (figure below). Individuals diagnosed with HIV-1, HBV, or
      HCV infections should be tested for coinfections and counseled to prevent
      acquisitions of similarly transmitted infections.

PMID- 21879789
TI  - Calculation of diagnostic parameters of advanced serological and molecular tissue
      print methods for detection of Citrus tristeza virus: a model for other plant
      pathogens.
AB  - Citrus tristeza virus (CTV) is one of the most important virus diseases that
      affect citrus. Control of CTV is achieved by grafting selected virus-free citrus
      scions onto CTV-tolerant or -resistant rootstocks. Quarantine and certification
      programs are essential for avoiding the entry and propagation of severe strains
      of CTV. Citrus nurseries in Spain and central California (United States) maintain
      zero-tolerance policies for CTV that require sensitive, specific, and reliable
      pathogen-detection methods. Tissue-print (TP) real-time reverse-transcriptase
      polymerase chain reaction (RT-PCR) assay was compared with the validated TP
      enzyme-linked immunosorbent assay (ELISA), using the CTV-specific monoclonal
      antibodies 3DF1 and 3CA5, for CTV detection. In total, 1,395 samples from healthy
      and CTV-infected nursery and mature tree plants were analyzed with both methods.
      The total agreement between both detection methods was substantial (Cohen's kappa
      index of 0.77 +/- 0.03). The diagnostic parameters of each technique (i.e., the
      sensitivity, specificity, and likelihood ratios) were evaluated in a second test
      involving 658 Citrus macrophylla nursery plants. Mexican lime indexing was used
      to evaluate samples with discrepant results in the analysis. For TP-ELISA, a
      sensitivity of 0.8015, a specificity of 0.9963, and a positive and negative
      likelihood ratio of 216.42 and 0.199, respectively, were estimated. For TP real
      time RT-PCR, a sensitivity of 0.9820, a specificity of 0.8519, and a positive and
      negative likelihood ratio of 6.63 and 0.021, respectively, were estimated. These
      diagnostic parameters show that TP real-time RT-PCR was the most sensitive
      technique, whereas TP-ELISA showed the highest specificity, validating the use of
      the molecular technique for routine CTV-detection purposes. In addition, our
      results show that the combination of both techniques can accurately substitute
      for the conventional biological Mexican lime index for the detection of CTV. The
      calculation of diagnostic parameters is discussed, as a necessary tool, to
      validate detection or diagnostic methods in plant pathology. Furthermore,
      assessment of the post-test probability of disease after a diagnostic result and
      CTV prevalence allows selection of the best method for accurate and reliable
      diagnosis.

PMID- 21879790
TI  - Sequence and simple-sequence repeat analyses of the fungal pathogen Seiridium
      cardinale indicate California is the most likely source of the cypress canker
      epidemic for the Mediterranean region.
AB  - Seiridium cardinale is the pathogenic fungus of unknown origin responsible for a
      world pandemic known as cypress canker affecting several species of Cupressaceae
      in both the Northern and Southern Hemisphere. In this study, a comparative
      genetic analysis of worldwide populations was performed using sequence analysis
      of a portion of the ?-tubulin locus and seven polymorphic simple-sequence repeat
      (SSR) loci on 96 isolates. Sequence analysis identified two distinct ?-tubulin
      alleles, both present in California. Only one of the two alleles was detected in
      the Mediterranean basin, while two isolates from the Southern Hemisphere were
      characterized by the presence of the allele absent from the Mediterranean. SSRs
      identified a total of 46 multilocus genotypes (MGs): genotypic diversity was
      always higher in the California population, and calculations of the index of
      association (I(A)) determined the presence of linkage disequilibrium associated
      with the absence of sexual reproduction only in the Mediterranean population but
      not in California. In 50 instances, the same MG was found at great geographic
      distances, implying a role played by humans in spreading the disease. Network
      analysis performed on SSR data identified three clusters of MGs: California,
      Morocco, and the rest of the Mediterranean. Both the Morocco and the
      Mediterranean clusters were linked to the California cluster. Coalescent analysis
      identified insignificant migration between California and Italy, as expected in
      the presence of a single introduction event, and very high migration from Italy
      into Greece, as expected of an outbreak still in exponential growth phase and
      starting from an Italian source.

PMID- 21879791
TI  - Colonization and movement of GFP-labeled Clavibacter michiganensis subsp.
      michiganensis during tomato infection.
AB  - The vascular pathogen Clavibacter michiganensis subsp. michiganensis is
      responsible for bacterial wilt and canker of tomato. Pathogenicity of this
      bacterium is dependent on plasmid-borne virulence factors and serine proteases
      located on the chromosomal chp/tomA pathogenicity island (PAI). In this study,
      colonization patterns and movement of C. michiganensis subsp. michiganensis
      during tomato infection was examined using a green fluorescent protein (GFP)
      labeled strain. A plasmid expressing GFP in C. michiganensis subsp. michiganensis
      was constructed and found to be stable in planta for at least 1 month. Confocal
      laser-scanning microscopy (CLSM) of inoculated stems showed that the pathogen
      extensively colonizes the lumen of xylem vessels and preferentially attaches to
      spiral secondary wall thickening of the protoxylem. Acropetal movement of the
      wild-type strain C. michiganensis subsp. michiganensis NCPPB382 (Cmm382) in
      tomato resulted in an extensive systemic colonization of the whole plant reaching
      the apical region after 15 days, whereas Cmm100 (lacking the plasmids pCM1 and
      pCM2) or Cmm27 (lacking the chp/tomA PAI) remained confined to the area
      surrounding of the inoculation site. Cmm382 formed biofilm-like structures
      composed of large bacterial aggregates on the interior of xylem walls as observed
      by CLSM and scanning electron microscopy. These findings suggest that virulence
      factors located on the chp/tomA PAI or the plasmids are required for effective
      movement of the pathogen in tomato and for the formation of cellular aggregates.

PMID- 21879792
TI  - Detection and quantification of Pratylenchus thornei in DNA extracted from soil
      using real-time PCR.
AB  - The root-lesion nematode Pratylenchus thornei is one of the most important pests
      restricting productivity of wheat in the Pacific Northwest (PNW). It is laborious
      and difficult to use microscopy to count and identify the nematodes in soils. A
      SYBR Green I-based real-time polymerase chain reaction (PCR) assay was developed
      to detect and quantify this species from DNA extracts of soil. A primer set,
      designed from the internal transcribed spacer region (ITS1) of rDNA, was highly
      specific to P. thornei and did not amplify DNA from 27 isolates of other
      Pratylenchus spp., other nematodes, and six fungal species present in PNW wheat
      fields. A standard curve relating threshold cycle and log values of nematode
      number was generated from artificially infested soils. The standard curve was
      supported by a high correlation between the numbers of P. thornei added to soil
      and the numbers quantified using real-time PCR. Examination of 15 PNW dryland
      field soils and 20 greenhouse samples revealed significant positive correlations
      between the numbers determined by real-time PCR and by the Whitehead tray and
      microscopic method. Real-time PCR is a rapid, sensitive alternative to time
      consuming nematode extractions, microscopic identification, and counting of P.
      thornei from field and greenhouse soils.

PMID- 21879793
TI  - Comparison of three-dimensional orthodontic load systems of different commercial
      archwires for space closure.
AB  - OBJECTIVE: To experimentally quantify the effects of the loop design on three
      dimensional orthodontic load systems of two types of commercial closing loop
      archwires: Teardrop and Keyhole. MATERIALS AND METHODS: An orthodontic force
      tester and custom-made dentoform were used to measure the load systems produced
      on two teeth during simulated space closure. The system included three force
      components along and three moment components about three clinically defined axes
      on two target teeth: the left maxillary canine and the lateral incisor. The
      archwires were attached to the dentoform and were activated following a standard
      clinical procedure. RESULTS: The resulting six load components produced by the
      two archwires were reported and compared. The results were also compared with
      those of the T-loop archwire published previously. CONCLUSIONS: The three designs
      deliver similar loading patterns; however, the component magnitudes are dependent
      on the design. All of the designs result in lingual tipping of the teeth, canine
      lingual-mesial displacement, canine crown-mesial-in rotation, and incisor crown
      distal-in rotation.

PMID- 21879794
TI  - Small antral follicle count (2-5 mm) and ovarian volume for prediction of
      pregnancy in in vitro fertilization cycles.
AB  - AIMS: To assess the value of antral follicle count (AFC) and other parameters as
      predictors of pregnancy in in vitro fertilization (IVF). METHODS: In a cohort
      study, unselected consecutive women in IVF treatment were evaluated. Pretreatment
      parameters included AFC (subpopulations of small (2-5 mm) and large (5-10 mm)
      AFC), ovarian volume, and ovarian stroma Doppler indices. RESULTS: The study
      included 115 women of whom 38 (33%) were pregnant. Total AFC was significantly
      higher in the pregnant than in the non-pregnant group (13.7 +/- 5.8 vs. 11.3 +/-
      5.3, p = 0.034). On receiver operator characteristic (ROC) curve analysis, the
      pretreatment variables that were significantly associated with pregnancy were
      small AFC (2-5 mm), total AFC, and ovarian volume/AFC ratio. Women with a
      positive score (total AFC >15; small AFC (2-5 mm) >10; ovarian volume in
      mm(3)/AFC, <1400), had a significantly higher number of retrieved oocytes and a
      higher pregnancy rate than women with a negative score (12.1 +/- 5.1 vs. 8.7 +/-
      5.0, p = 0.027 and 58.3% vs. 30.1%, p = 0.049, respectively). On multivariate
      logistic regression analysis, total AFC was the only significant and independent
      predictor of pregnancy (p = 0.034). CONCLUSION: Pretreatment small AFC and
      ovarian volume may identify women with a higher probability to achieve pregnancy
      in IVF.

PMID- 21879795
TI  - Post-menopausal hormone therapy reduces autoantibodies to oxidized apolipoprotein
      B100.
AB  - The aim of the study was to verify whether post-menopausal hormone replacement
      therapy (HRT) modifies autoantibody titers against oxidized low-density
      lipoprotein (LDL) (anti-LDLoxi), against epitopes of oxidized apolipoprotein B100
      and common carotid intima-media thickness (IMT) in these women. Sixty-eight women
      in pre-menopause (PMW) and 216 in post-menopause (POMW) were recruited; eighty
      three had undergone HRT for at least 12 months, where 48 received conjugated
      estrogens alone (EHRT) and 35 received conjugated estrogen and
      medroxyprogesterone acetate (CHRT). ELISA was used to determine autoantibodies.
      Lipoprotein lipase (LPL), hepatic lipase (HL), cholesterol ester transfer protein
      (CETP) and phospholipid transfer protein (PLTP) activities were assayed by
      radiometric methods. IMT was measured using Doppler ultrasound. Anti-oxidized LDL
      and anti-D antibodies increased by 40% (p <= 0.003) and 42% (p <= 0.006),
      respectively, with menopause. There was a surprising and significant 7% reduction
      in anti-D2 antibody titers with HRT (p <= 0.050), indicating a positive effect of
      treatment on the immune response to oxidized LDL. Combined HRT decreased
      activities of HL and LPL. HRT did not change common carotid IMT, which was
      increased by 32% as expected after menopause (p <= 0.030). This study describes,
      for the first time, the protective effect of HRT on decreasing autoantibody
      titers against oxidized apolipoprotein B in LDL.

PMID- 21879796
TI  - A role for Bradyrhizobium japonicum ECF16 sigma factor EcfS in the formation of a
      functional symbiosis with soybean.
AB  - Alternative sigma (sigma) factors, proteins that recruit RNA polymerase core
      enzyme to target promoters, are one mechanism by which bacteria transcriptionally
      regulate groups of genes in response to environmental stimuli. A class of
      sigma(70) proteins, termed extracytoplasmic function (ECF) sigma factors, are
      involved in cellular processes such as bacterial stress responses and virulence.
      Here, we describe an ECF16 sigma factor, EcfS (Blr4928) from the gram-negative
      soil bacterium Bradyrhizobium japonicum USDA110, that plays a critical role in
      the establishment of a functional symbiosis with soybean. Nonpolar insertional
      mutants of ecfS form immature nodules that do not fix nitrogen, a defect that can
      be successfully complemented by expression of ecfS. Overexpression of the
      cocistronic gene, tmrS (blr4929), phenocopies the ecfS mutant in planta and,
      therefore, we propose that TmrS is a negative regulator of EcfS, a determination
      consistent with the prediction that it encodes an anti-sigma factor. Microarray
      analysis of the ecfS mutant and tmrS overexpressor was used to identify 40
      transcripts misregulated in both strains. These transcripts primarily encode
      proteins of unknown and transport-related functions and may provide insights into
      the symbiotic defect in these strains.

PMID- 21879797
TI  - Environmental risk factors and their impact on the age of onset of schizophrenia:
      Comparing familial to non-familial schizophrenia.
AB  - BACKGROUND AND AIMS: Several risk factors for schizophrenia have yet been
      identified. The aim of our study was to investigate how certain childhood and
      adolescent risk factors predict the age of onset of psychosis in patients with
      and without a familial component (i.e. a relative with schizophrenia or
      schizoaffective disorder). METHODS: Aside from the age of onset of psychosis, we
      examined the risk factors for schizophrenia including obstetric complications,
      birth during winter or spring, behavioral deviances or delayed motor and speech
      development, exposure to adverse life events and exposure to substance use within
      a group of 100 patients (45 female, 55 male) with a mean age (+/- standard
      deviation) of 35.15 +/- 13.21. RESULTS: Birth complications and cannabis abuse
      are predictors for an earlier onset of schizophrenia in patients with non
      familial schizophrenia. No environmental risk factors for an earlier age of onset
      in familial schizophrenia have been identified. CONCLUSIONS: Certain
      environmental risk factors for schizophrenia seem to have an impact on the age of
      onset of psychosis in non-familial schizophrenia, they do not seem to have an
      impact on familial schizophrenia.

PMID- 21879798
TI  - Pregnancy in heart- and heart/lung recipients can be problematic.
AB  - OBJECTIVE: The first successful pregnancy after heart transplantation was
      reported in 1988. Worldwide experience with heart and heart/lung transplanted (H
      HLTx) pregnant women is limited. To expand this knowledge the collaborating
      Nordic thoracic transplant centers wanted to collect information on all such
      pregnancies from their centers. DESIGN: Information was retrospectively collected
      on all H-HLTx pregnancies in the Nordic countries. RESULTS: A total of 25 women
      have had 42 pregnancies and all survived the gestation. Minor complications were
      increasing incidence of proteinuria, hypertension and diabetes. Major problems
      were two rejections (early post partum), two severe renal failures, seven pre
      eclampsias and 17 abortions. Five women died two to 12 years after delivery. Of
      25 live born children, one was born with cancer and one died early after
      inheriting the mother's cardiomyopathy. CONCLUSION: Pregnancy after H-HLTx can be
      successful for both mother and child. There are, however, many obstacles which
      should be addressed. Respecting the couple's desire for children the attitude
      should be carefully, not too optimistic, after proper pre-pregnant information
      and counseling. Delivery should preferably take place at the transplant center.

PMID- 21879799
TI  - Changes in the brain activation balance in motor-related areas after constraint
      induced movement therapy; a longitudinal fMRI study.
AB  - PRIMARY OBJECTIVE: This study investigated the longitudinal changes in brain
      activation balance in motor-related areas after Constraint-Induced Movement
      Therapy (CIMT). METHODS AND PROCEDURES: The subjects included seven ischemic
      stroke patients with mild right hemiparesis. Eight normal subjects were also
      included. The patients underwent functional MRI and motor function tests (Fugl
      Meyer Assessment; FMA, modified Wolf Motor Function Test; mWMFT) both before and
      immediately after CIMT and also after a 3-month follow-up. RESULTS: The motor
      function test scores improved immediately after CIMT; moreover, these scores were
      either maintained or improved even at the 3-month follow-up. In a comparison of
      the chronological data of the contralaterality index of the affected hand
      movement, the cerebellar activity changed significantly to ipsilateral activation
      immediately after CIMT and thereafter the cerebellar activity further changed to
      ipsilateral activation at the 3-month follow-up. A correlation was observed among
      the contralateral activation, FMA and mWMFT scores in SM1 and the ipsilateral
      activation and in the mWMFT scores in the cerebellum at the 3-month follow-up
      examinations. CONCLUSION: The participation of the contralateral SM1 and the
      ipsilateral cerebellum is thus considered to play an important role in the
      satisfactory recovery of the motor function after CIMT intervention.

PMID- 21879800
TI  - Minor adverse effects of galvanic vestibular stimulation in persons with stroke
      and healthy individuals.
AB  - OBJECTIVE: Galvanic vestibular stimulation (GVS) induces polarity-specific
      activations in the vestibular nerves and upstream in the vestibular and
      parietotemporal cortices as well as sub-cortical regions. This makes it an
      attractive technique for cognitive neuromodulation. However, systematic studies
      regarding adverse effects of GVS are unavailable. Thus, this study assessed
      adverse effects during and after sub-sensory GVS (mean: 0.6 mA) and GVS with 1.5
      mA. METHODS: Two hundred and fifty-five GVS sessions delivered to 55 persons with
      stroke and 30 healthy individuals were analysed using a 34-item-questionnaire
      including potential symptoms and rating scales for adverse effects. RESULTS: The
      most frequent symptoms during and after GVS were slight itching (mean: 10.2%) and
      tingling (mean: 10.7%) underneath the electrodes. Healthy individuals and persons
      with stroke did not differ in their incidence and rated intensity of adverse
      effects, nor did persons with or without unilateral spatial neglect. Adverse
      effects were found more frequently with GVS with 1.5 mA as with sub-sensory GVS.
      Participants were unable to differentiate real from sham conditions during sub
      sensory GVS. Importantly, neither seizures nor vertigo or nausea were observed.
      CONCLUSION: Sub-sensory GVS and GVS with 1.5 mA induce very few and mild adverse
      effects in healthy and persons with stroke and are safe when safety guidelines
      are followed.

PMID- 21879801
TI  - Microvascular occlusions and coronary microembolization.

PMID- 21879803
TI  - A critical review of Salmonella Typhimurium infection in laying hens.
AB  - Salmonella Typhimurium has been reported to contaminate egg production across the
      world, but where Salmonella Enteritidis is endemic it is this latter serovar that
      dominates egg-borne salmonellosis. However, Salmonella Typhimurium is a major
      food-borne pathogen so it is important to understand how it can impact the
      microbiological safety of eggs and what serovar-specific control strategies may
      be appropriate in the future as control over Salmonella Enteritidis continues to
      improve. To that end, the present review examines the published literature on
      Salmonella Typhimurium in laying hens and eggs, with particular reference to
      comparative studies examining different serovars. Experimentally Salmonella
      Enteritidis is more often isolated from egg contents and seems to adhere better
      to reproductive tract mucosa, whilst Salmonella Typhimurium appears to provoke a
      more intense tissue pathology and immune response, and flock infections are more
      transient. However, it is observed in many cases that the present body of
      evidence does not identify clear differences between specific behaviours of the
      serovars Typhimurium and Enteritidis, whether in laying hens, in their eggs, or
      in the laying environment. It is concluded that further long-term experimental
      and natural infection studies are needed in order to generate a clearer picture.

PMID- 21879802
TI  - Human herpesvirus 6 and cytomegalovirus in ileocolonic mucosa in inflammatory
      bowel disease.
AB  - OBJECTIVES: Reactivation of a latent cytomegalovirus (CMV) may occur in
      inflammatory bowel disease (IBD). Data of human herpesvirus 6 (HHV-6)--a close
      relative to CMV--in active IBD are scarce. The aim of this study was to detect
      HHV-6 and CMV antigens in the mucosa of active and inactive IBD. MATERIAL AND
      METHODS: 79 IBD patients (47 ulcerative colitis (UC) and 32 Crohn's disease (CD))
      were recruited and endoscopic and histological disease activity was scored.
      Control group consisted of 15 non-IBD patients with normal colonoscopy.
      Immunohistochemical stainings for HHV-6B and CMV antigens were performed on
      biopsy specimens from the ileum and colorectum. The intensity of HHV-6B and CMV
      expression was graded as negative, mild, moderate, or intense. RESULTS: HHV-6B
      antigen was positive in 35 (44%) and CMV in 64 (81%). Of controls, 6 (40%) were
      mildly positive for HHV-6 and 6 (40%) for CMV. In IBD, both CMV and HHV-6B
      intensity correlated with endoscopic disease severity (CMV p = 0.010 and HHV-6 p
      = 0.048). Simultaneous HHV-6B and CMV antigen expression occurred in 29 (37%) and
      associated with endoscopic activity (p = 0.006) and to a number of
      immunosuppressives (p = 0.033). A significant difference in HHV-6B positivity was
      found between endoscopically active and inactive UC (p = 0.040). Both CMV and HHV
      6B intensity correlated with histological severity in the rectal biopsy specimens
      (for CMV p = 0.040 and for HHV-6B p = 0.027). CONCLUSIONS: Both viruses occurred
      ubiquitously in the IBD mucosa. Coexistence of viruses was common and associated
      with disease activity and use of immunosuppressives. HHV-6B intensity correlated
      with endoscopic severity in UC.

PMID- 21879804
TI  - Lynch syndrome screening in newly diagnosed colorectal cancer in general
      pathology practice: from the revised Bethesda guidelines to a universal approach.
AB  - OBJECTIVE: Lynch syndrome (LS) is the most common hereditary form of colorectal
      cancer (CRC). The revised 2004 Bethesda guidelines were developed to identify
      potential LS patients. This study aimed to retrospectively evaluate utilization
      and adequacy of the guidelines in general pathology practice and to determine if
      a universal LS screening approach increased the potential LS detection rate in
      newly diagnosed CRCs. MATERIAL AND METHODS: Included were 445 primary CRCs
      surgically resected from November 2006 to March 2009, when reflex microsatellite
      instability (MSI) testing was based on histomorphology and age as well as 145
      CRCs resected from July 2009 to July 2010 when a universal LS testing paradigm
      was used. Reflex MSI testing rates and MSI testing results were determined.
      RESULTS: The overall LS screening rate from November 2006 to March 2009 was
      34.8%, and the extrapolated microsatellite instability-high (MSI-H) rate was 8.5%
      (38/445). Strict adherence to the revised Bethesda guidelines, that is, without
      testing CRC diagnosed in patients ?60 years, would have missed 26 (68.4%) MSI-H
      CRCs. The overall LS screening rate from July 2009 to July 2010 was 76.3% and the
      MSI-H rate was 20.6% (30/145). Compared with the MSI tested group, the untested
      group had more CRCs removed by local excision (22.2% vs. 4.8%, p = 0.00035).
      CONCLUSION: The revised Bethesda guidelines are inadequate for LS screening when
      personal and family cancer history is not available to the pathologist, a
      universal screening paradigm greatly increased the rate of MSI testing and MSI-H
      CRC detection and CRCs less likely to be screened for LS were those diagnosed in
      locally excised specimens.

PMID- 21879805
TI  - Fatal case of ectopic enterobiasis: Enterobius vermicularis in the kidneys.
AB  - Enterobius vermicularis is one of the most common intestinal parasites found in
      humans. They commonly infest the terminal ileum and large intestine, and are
      usually considered an innocuous parasite that can be easily eradicated with
      proper treatment. However, extraintestinal migration of worms, although very
      rare, may lead to severe health disorders or even death. This article, reports
      the first fatal case of ectopic enterobiasis known to the authors, which
      developed in an adult patient with E. vermicularis infection, causing perforation
      of the large intestine and generalized bacterial peritonitis. Despite emergency
      laparotomy, the patient died from septic shock on the day after surgery. During
      pathological examination, worms were found not only in the large intestine, but
      also in the renal parenchyma; worm eggs were found deposited in the lungs as
      well.

PMID- 21879806
TI  - Resolving the theory of planned behaviour's 'expectancy-value muddle' using
      dimensional salience.
AB  - The theory of planned behaviour is one of the most widely used models of decision
      making in the health literature. Unfortunately, the primary method for assessing
      the theory's belief-based expectancy-value models results in statistically
      uninterpretable findings, giving rise to what has become known as the 'expectancy
      value muddle'. Moreover, existing methods for resolving this muddle are
      associated with various conceptual or practical limitations. This study addresses
      these issues by identifying and evaluating a parsimonious method for resolving
      the expectancy-value muddle. Three hundred and nine Australian residents aged 18
      24 years rated the expectancy and value of 18 beliefs about posthumous organ
      donation. Participants also nominated their five most salient beliefs using a
      dimensional salience approach. Salient beliefs were perceived as being more
      likely to eventuate than non-salient beliefs, indicating that salient beliefs
      could be used to signify the expectancy component. The expectancy-value term was
      therefore represented by summing the value ratings of salient beliefs, an
      approach that predicted attitude (adjusted R2 = 0.21) and intention (adjusted R2
      = 0.21). These findings suggest that the dimensional salience approach is a
      useful method for overcoming the expectancy-value muddle in applied research
      settings.

PMID- 21879807
TI  - Similar effects of visual perception and imagery on simple reaction time.
AB  - A longstanding issue is whether perception and mental imagery share similar
      cognitive and neural mechanisms. To cast further light on this problem, we
      compared the effects of real and mentally generated visual stimuli on simple
      reaction time (RT). In five experiments, we tested the effects of difference in
      luminance, contrast, spatial frequency, motion, and orientation. With the
      intriguing exception of spatial frequency, in all other tasks perception and
      imagery showed qualitatively similar effects. An increase in luminance, contrast,
      and visual motion yielded a decrease in RT for both visually presented and
      imagined stimuli. In contrast, gratings of low spatial frequency were responded
      to more quickly than those of higher spatial frequency only for visually
      presented stimuli. Thus, the present study shows that basic dependent variables
      exert similar effects on visual RT either when retinally presented or when
      imagined. Of course, this evidence does not necessarily imply analogous
      mechanisms for perception and imagery, and a note of caution in such respect is
      suggested by the large difference in RT between the two operations. However, the
      present results undoubtedly provide support for some overlap between the
      structural representation of perception and imagery.

PMID- 21879808
TI  - U-shaped association between body mass index and the prevalence of wheeze and
      asthma, but not eczema or rhinoconjunctivitis: the ryukyus child health study.
AB  - BACKGROUND: Studies reporting on the association between obesity and allergies
      have mostly focused on asthma. Little is known about the relationship of obesity
      to other allergic diseases, and the information that is available has been
      inconsistent. We examined the association between body mass index (BMI) and the
      prevalence of wheeze, asthma, eczema, and rhinoconjunctivitis in Japanese
      schoolchildren. METHODS: Study subjects were 24,399 children aged 6-15 years in
      Okinawa, Japan. Outcomes were based on diagnostic criteria from the International
      Study of Asthma and Allergies in Childhood. BMI was categorized into five groups;
      <5th, 5th to 35th, >35th to 65th, >65th to 95th, and >95th percentile groups.
      Adjustment was made for sex, age, region of residence, number of siblings,
      smoking in the household, physical activity, paternal and maternal history of
      allergic disorders, and paternal and maternal educational levels. RESULTS: The
      prevalence values of wheeze, asthma, eczema, and rhinoconjunctivitis in the
      previous 12 months were 10.8%, 7.6%, 6.9%, and 7.6%, respectively. Compared with
      the referent category (>35th to 65th percentile group), higher percentile
      categories were positively associated with the prevalence of wheeze. A U-shaped
      relationship between BMI and asthma was observed. No material associations
      between BMI percentile categories and the prevalence of eczema or
      rhinoconjunctivitis were found. CONCLUSION: These findings suggested that being
      either underweight or overweight might increase the likelihood of asthma among
      Japanese schoolchildren.

PMID- 21879809
TI  - Final results of a multicenter phase 1 study of lenalidomide in patients with
      relapsed or refractory chronic lymphocytic leukemia.
AB  - Based on clinical activity in phase 2 studies, lenalidomide was evaluated in a
      phase 2/3 study in patients with relapsed/refractory chronic lymphocytic leukemia
      (CLL). Following tumor lysis syndrome (TLS) complications, the protocol was
      amended to a phase 1 study to identify the maximum tolerated dose-escalation
      level (MTDEL). Fifty-two heavily pretreated patients, 69% with bulky disease and
      48% with high-risk genomic abnormalities, initiated lenalidomide at 2.5 mg/day,
      with dose escalation until the MTDEL or the maximum assigned dose was attained.
      Lenalidomide was safely titrated to 20 mg/day; the MTDEL was not reached. Most
      common grade 3-4 adverse events were neutropenia and thrombocytopenia; TLS was
      mild and rare. The low starting dose and conservative dose escalation strategy
      resulted in six partial responders and 30 patients obtaining stable disease. In
      summary, lenalidomide 2.5 mg/day is a safe starting dose that can be titrated up
      to 20 mg/day in patients with CLL.

PMID- 21879810
TI  - Three cases of primary cutaneous lymphoblastic lymphoma: microarray-based
      comparative genomic hybridization and gene expression profiling studies with
      review of literature.
AB  - Lymphoblastic lymphoma (LBL) is a neoplasm of precursor B- or T-lymphocytes, and
      primary skin involvement is uncommon. The aim of the study was to review all
      reported primary cutaneous (PC)-LBLs and to examine three new cases to better
      characterize this neoplasm. Two of our patients showed a pre-B phenotype (PC-B
      LBL) and one a never-reported pre-T phenotype (PC-T-LBL). The patient with PC-T
      LBL showed an aggressive course, while those with PC-B-LBL showed a complete
      remission (CR) after polychemotherapy. Cytogenetic analysis and gene expression
      profiling (GEP) were performed on one case of PC-B-LBL and on that of PC-T-LBL. A
      specimen of PC-B-LBL and two specimens (early and late stage) of PC-T-LBL were
      investigated by microarray-based comparative genomic hybridization (CGH). All
      specimens revealed trisomy of chromosome 4. PC-T-LBL showed a gain of 1p36.33
      p22.1 in the early stage and multiple chromosome gains/losses in the late stage.
      Our data suggest that trisomy 4 could be detected early in LBL and gain of
      1p36.33-p22.1 could be an interesting marker in PC-T-LBL. LBL is an aggressive
      disease but, only in B-LBL, the cutaneous presentation seems to be a favorable
      prognostic factor and polychemotherapy is the best therapeutic approach. We
      suggest that PC-LBL should be included as a provisional clinicopathologic entity
      in future cutaneous lymphoma classification.

PMID- 21879812
TI  - Predictors of physicians' attitudes toward sharing information with patients and
      addressing psychosocial needs: a cross-sectional study in Greece.
AB  - Sharing information with patients and addressing their psychosocial needs are
      recognized as fundamental practices of patient-centered physicians. Our study
      explored predictors of physicians' patient-centered attitudes and yielded a
      better understanding of the relative influences of job satisfaction, employment
      status, specialty, previous communication skills training, and sociodemographic
      factors. Physicians who participated in 13 identical workshops offered throughout
      Greece were invited to complete a battery of anonymous questionnaires
      (demographics, job satisfaction scale, Patient-Practitioner Orientation Scale
      Sharing subscale, and Physician Belief Scale). Prediction models were used to
      identify predictors of patient-centered attitudes. In total, 400 fully completed
      questionnaires were returned (response rate 79.8%). Job satisfaction, previous
      training in communication skills, younger age and lower socioeconomic status were
      predictors of positive attitudes toward sharing information with patients. Job
      satisfaction, previous training in communication skills, and stronger religious
      beliefs were predictors of higher psychosocial orientation. Job satisfaction and
      training in communication skills should be ensured in the effort to develop and
      maintain patient-centered attitudes in physicians. Religious beliefs, age, and
      socioeconomic status should be taken into consideration in the effort to help
      physicians become aware of their biases.

PMID- 21879811
TI  - A novel Aurora kinase A inhibitor MK-8745 predicts TPX2 as a therapeutic
      biomarker in non-Hodgkin lymphoma cell lines.
AB  - Selective small-molecule kinase inhibitors have encouraging clinical efficacy in
      several malignancies. These agents are still limited to a subset of patients,
      indicating the need to develop therapeutic biomarkers that influence clinical
      benefit. In this study, we demonstrate that treatment with MK-8745, a novel
      Aurora-A specific inhibitor, leads to cell cycle arrest at the G2/M phase with
      accumulation of tetraploid nuclei followed by cell death in non-Hodgkin lymphoma
      (NHL) cell lines. The sensitivity of the cell lines to MK-8745 is correlated with
      the expression level of Aurora-A activator. The siRNA knockdown of Aurora-A
      activator TPX2 (targeting protein for Xenopus kinase-like protein 2) increased MK
      8745 sensitivity in less-MK-8745-sensitive NHL cell lines, whereas overexpression
      of TPX2 in high-MK-8745-sensitive NHL cell lines increased drug resistance. Our
      results indicate that TPX2 may serve as a biomarker for identifying
      subpopulations of patients sensitive to Aurora-A inhibitor treatment.

PMID- 21879813
TI  - Seeking and processing influenza vaccine information: a study of health care
      workers at a large urban hospital.
AB  - In response to low influenza vaccination rates among health care workers, health
      officials have explored determinants of uptake and developed communication
      interventions. Key to these efforts is how workers seek and attend to vaccine
      information. We applied a model of risk information seeking and processing to
      survey 226 physicians and nurses at a large, urban hospital (response rate =
      5.7%; cooperation rate = 91.5%). Our goals were to (1) apply the model to a new
      setting, audience, and issue and (2) explore novel concepts (e.g., source
      credibility and information usefulness) and moderating relationships among
      variables. Consistent with previous research, information subjective norms
      perceived social pressure to remain informed about vaccination-were a strong
      predictor of information seeking and systematic processing. Neither source
      credibility nor information usefulness independently increased explained
      variance, although they moderated the relationship between norms and
      communication behavior. We discuss theoretical and practical implications of
      these findings.

PMID- 21879814
TI  - Pumice as a remarkable substrate for the origin of life.
AB  - The context for the emergence of life on Earth sometime prior to 3.5 billion
      years ago is almost as big a puzzle as the definition of life itself. Hitherto,
      the problem has largely been addressed in terms of theoretical and experimental
      chemistry plus evidence from extremophile habitats like modern hydrothermal vents
      and meteorite impact structures. Here, we argue that extensive rafts of glassy,
      porous, and gas-rich pumice could have had a significant role in the origin of
      life and provided an important habitat for the earliest communities of
      microorganisms. This is because pumice has four remarkable properties. First,
      during eruption it develops the highest surface-area-to-volume ratio known for
      any rock type. Second, it is the only known rock type that floats as rafts at the
      air-water interface and then becomes beached in the tidal zone for long periods
      of time. Third, it is exposed to an unusually wide variety of conditions,
      including dehydration. Finally, from rafting to burial, it has a remarkable
      ability to adsorb metals, organics, and phosphates as well as to host organic
      catalysts such as zeolites and titanium oxides. These remarkable properties now
      deserve to be rigorously explored in the laboratory and the early rock record.

PMID- 21879815
TI  - Redefining diagnostic symptoms of depression using Rasch analysis: testing an
      item bank suitable for DSM-V and computer adaptive testing.
AB  - OBJECTIVE: We aimed to redefine the optimal self-report symptoms of depression
      suitable for creation of an item bank that could be used in computer adaptive
      testing or to develop a simplified screening tool for DSM-V. METHOD: Four hundred
      subjects (200 patients with primary depression and 200 non-depressed subjects),
      living in Iraqi Kurdistan were interviewed. The Mini International
      Neuropsychiatric Interview (MINI) was used to define the presence of major
      depression (DSM-IV criteria). We examined symptoms of depression using four well
      known scales delivered in Kurdish. The Partial Credit Model was applied to each
      instrument. Common-item equating was subsequently used to create an item bank and
      differential item functioning (DIF) explored for known subgroups. RESULTS: A
      symptom level Rasch analysis reduced the original 45 items to 24 items of the
      original after the exclusion of 21 misfitting items. A further six items (CESD13
      and CESD17, HADS-D4, HADS-D5 and HADS-D7, and CDSS3 and CDSS4) were removed due
      to misfit as the items were added together to form the item bank, and two items
      were subsequently removed following the DIF analysis by diagnosis (CESD20 and
      CDSS9, both of which were harder to endorse for women). Therefore the remaining
      optimal item bank consisted of 17 items and produced an area under the curve
      (AUC) of 0.987. Using a bank restricted to the optimal nine items revealed only
      minor loss of accuracy (AUC = 0.989, sensitivity 96%, specificity 95%). Finally,
      when restricted to only four items accuracy was still high (AUC was still 0.976;
      sensitivity 93%, specificity 96%). CONCLUSIONS: An item bank of 17 items may be
      useful in computer adaptive testing and nine or even four items may be used to
      develop a simplified screening tool for DSM-V major depressive disorder (MDD).
      Further examination of this item bank should be conducted in different cultural
      settings.

PMID- 21879817
TI  - Changing attitudes in ovarian stimulation.

PMID- 21879819
TI  - Estradiol valerate and dienogest: a novel four-phasic oral contraceptive pill
      effective for pregnancy prevention and treatment of heavy menstrual bleeding.
AB  - Estradiol valerate and dienogest have been combined to create a novel four-phasic
      oral contraceptive pill effective for both pregnancy prevention and treatment of
      heavy menstrual bleeding. This formulation represents the only oral contraceptive
      pill available in the USA containing an estrogen component that is biologically
      active as the endogenous estrogen 17beta-estradiol. This medication was developed
      out of efforts to replace the most common estrogen in contraceptive pills,
      ethinyl estradiol, which is known to be a potent inducer of hepatic protein
      synthesis. Estradiol valerate has been available since the 1970s in oral and
      injectable forms indicated for the treatment of menopausal climacteric symptoms.
      Dienogest has been used in other oral contraceptive pills for over 10 years.
      Previous attempts to develop an oral contraceptive pill with natural estradiol or
      estradiol valerate were unsuccessful due to poor cycle control. A novel dynamic
      dosing regimen was devised to improve the bleeding pattern. This medication has
      been shown in several clinical trials to have good contraceptive efficacy and
      cycle control. Recent studies have also demonstrated that this medication is
      effective for the treatment of heavy menstrual bleeding. However, compared with
      other oral contraceptive pills, this medication is associated with a higher
      frequency of absent withdrawal bleeding. Furthermore, the dynamic dosing regimen
      requires relatively complex instructions for users who miss pills.

PMID- 21879816
TI  - Vaginal progesterone to reduce the rate of preterm birth and neonatal morbidity:
      a solution at last.

PMID- 21879820
TI  - Hemochromatosis and ovarian cancer.
AB  - Evaluation of: Gannon PO, Medelci S, Le Page C et al. Impact of hemochromatosis
      gene (HFE) mutations on epithelial ovarian cancer risk and prognosis. Int. J.
      Cancer 128(10), 2326-2334 (2011). The frequency of two mutations (C282Y and D62H)
      of the hemochromatosis gene were investigated in women with ovarian cancer. A
      single allele mutation of the C282Y but not the H63D gene product was detected in
      8-9% of women with benign ovarian tumors (n = 124) and ovarian cancers (n = 360)
      compared with 2.5% for controls (n = 80) representing a 4.9-fold increase in
      risk. With high-grade serous ovarian cancers (n = 179), the survival rate of
      women with a single allele C282Y mutation was reduced from 39 to 19 months. These
      results implicate mutations of the hemochromatosis gene in the generation and
      severity of ovarian cancers, which may have prognostic value.

PMID- 21879821
TI  - Surgery for recurrent ovarian cancer.
AB  - Cytoreductive surgery is accepted as a major treatment of primary ovarian cancer.
      The role in recurrent ovarian cancer remains a field of discussion and
      controversy, mainly owing to missing data from prospective randomized trials and
      lack of universal definitions. Retrospective data indicate that complete
      resection of recurrent tumor formations should be aimed for, since survival
      prolongation is mainly seen for patients with no residual disease. Thus, it is
      most important to find predictors of complete resection, on the one hand to offer
      the best therapeutic chances to patients, but on the other hand to protect
      patients with limited life expectancy from additional surgical burden. The first
      prospective surgical trial in recurrent ovarian cancer, AGO-DESKTOP II validated
      a score ('AGO score') for complete resection. It was shown that patients with a
      good general condition (ECOG 0), no residual disease after surgery for primary
      ovarian cancer and absence of ascites in presurgical diagnostics have a 76%
      likelihood of undergoing complete resection. In this article, further recent data
      regarding surgery for recurrent ovarian cancer are going to be discussed and the
      advantages of incorporating these patients into randomized trials are
      highlighted.

PMID- 21879822
TI  - Fertility preservation in women with cancer: importance of a multidisciplinary
      approach.
AB  - For all patients affected by a disease that could impair fertility before or
      during the reproductive lifespan, strategies to preserve their fertility and the
      ability to bear their own children is likely to be of utmost importance. While
      fertility preservation is a promising option, most of the technologies currently
      used are far from being well-established or are still experimental. Patients
      should be aware that no method guarantees success. Psychological and ethical
      impacts of fertility preservation are major concerns and should be included in
      the multidisciplinary approach to the patients.

PMID- 21879823
TI  - Fertility, infertility and thrombophilia.
AB  - Hypercoagulation has been reported in some studies to be associated with
      reproductive failures, such as unexplained infertility, IVF implantation failure
      and recurrent fetal losses. Many pregnancy-related disorders have been
      interpreted as consequences of impaired microvascular function and might be
      viewed as a mild form of venous thromboembolic disease. In the absence of
      clinical guidelines, there is a need for an evidence base regarding thrombophilic
      screening and antithrombotic therapy in cases of reproductive failure. This
      article will focus on the controversial effect of congenital and acquired
      thrombophilia on human fertility, and will review the English literature for
      relevant studies identified by searching PubMed((r)) results between January 1966
      November 2010 using the key words: 'thrombophilia', 'fertility' and
      'infertility'.

PMID- 21879824
TI  - Pre-eclampsia, severe pre-eclampsia and hemolysis, elevated liver enzymes and low
      platelets syndrome: what is new?
AB  - Pre-eclampsia and eclampsia have been known to us for centuries. Significant
      improvements have been made in our knowledge of the disease, however, delivery
      remains the only effective form of treatment. There is widespread variation of
      practice in the management of hypertensive disease in pregnancy, which may lead
      to substandard care. The use of aspirin in preventing pre-eclampsia, the lack of
      correlation between urinary protein and adverse outcome, and the ineffectiveness
      of corticosteroids in the management of hemolysis and elevated liver enzymes and
      low platelets syndrome are a few of the developments that will alter the way this
      condition is managed. This article aims to provide a general overview of pre
      eclampsia, eclampsia and hemolysis, hemolysis and elevated liver enzymes and low
      platelets syndrome supported by the latest evidence, which will help the care
      provider adopt a focused approach and use the latest knowledge to understand and
      manage this old condition.

PMID- 21879825
TI  - Managing low sexual desire in women.
AB  - Low sexual desire is a prevalent symptom, but not one frequently volunteered by
      women. When accompanied by distress, loss of libido is known as hypoactive sexual
      desire disorder, which can have a significant impact on a woman's wellbeing. The
      etiology of hypoactive sexual desire disorder is multifactorial and its
      management requires a combination of psychosocial and pharmacological
      interventions. This article outlines the assessment of patients presenting with
      the symptom of low sexual desire and discusses the evidence for pharmacological
      management.

PMID- 21879826
TI  - Management of endometriosis-related pain: an update.
AB  - Endometriosis is a chronic and recurrent condition affecting 6-10% of women of a
      reproductive age. It results from implantation of endometrial tissue outside the
      uterine cavity. It is associated with pelvic pain and infertility. Treatment for
      endometriosis ranges from medical management, to conservative surgery, to
      definitive surgery with a hysterectomy and bilateral salpingo-oophorectomy, and
      should be based on patient's fertility desires and tolerance. Medical treatment
      involves hormonal manipulation to induce a hypoestrogenic or antiestrogenic state
      to induce regression and apoptosis of lesions. Endometriosis can have dire
      effects on women's lives and productivity; this article will focus on early
      diagnosis, treatment and prevention of recurrence of the disease.

PMID- 21879827
TI  - Safety of tranexamic acid in women with heavy menstrual bleeding: an open-label
      extension study.
AB  - AIMS: An open-label, extension clinical study was conducted to assess the safety
      of a novel, oral formulation of tranexamic acid (TA) in women with cyclic heavy
      menstrual bleeding. PATIENTS & METHODS: Eligible patients who completed either a
      three- or six-cycle double-blinded clinical trial of TA were offered enrollment
      into a study of nine cycles with TA (1.3 g orally three times/day for a maximum
      of 5 days per cycle). Safety was assessed by the incidence of treatment-emergent
      adverse events, ophthalmologic examinations and ECGs, among other evaluations.
      RESULTS: The most commonly reported treatment-emergent adverse events were
      menstrual discomfort (46.2%), headache (43.9%) and back pain (23.1%). A small
      proportion of participants (3.8%) reported ocular adverse events, but there was
      no evidence of ocular toxicity. No prothrombotic effects were observed.
      CONCLUSION: During nine menstrual cycles of treatment, this novel formulation of
      TA was well tolerated and exhibited a favorable safety profile supporting its use
      as a therapy for cyclic heavy menstrual bleeding.

PMID- 21879828
TI  - Nutritional status of Iranian women with rheumatoid arthritis: an assessment of
      dietary intake and disease activity.
AB  - BACKGROUND: Long-standing chronic diseases such as rheumatoid arthritis are known
      to be associated with impairment of nutritional status to some degree. The
      present study aimed to assess nutritional status of women with rheumatoid
      arthritis and compare their ingestion of certain micronutrients with dietary
      reference intakes. METHODS: In this cross-sectional study, 90 eligible women were
      recruited. After examination, all patients were evaluated on the basis of disease
      activity score, calculated using the number of tender and swollen joints, patient
      global assessment of pain and high sensitivity C-reactive protein (CRP). A three
      day 24 h recall was completed and a 10 ml fasting blood sample was obtained to
      assess the plasma levels of malondialdehyde, total antioxidant and CRP. RESULTS:
      Despite normal BMI, intake of energy and micronutrients including calcium, folic
      acid, zinc, magnesium and vitamin B6 were considerably lower compared with the
      dietary reference intakes. There was no significant relationship between intake
      of different nutrients or food groups and disease activity score and the
      biochemical markers including malondialdehyde, CRP and total antioxidant.
      CONCLUSIONS: Intake of energy and some micronutrients were significantly lower
      than the recommended values. However, no relationship was found between intake of
      different food groups or nutrients with disease activity or serum antioxidant
      capacity.

PMID- 21879829
TI  - Hypovitaminosis D3 in menopausal women in a tertiary care hospital in Delhi.
AB  - Blood samples from 126 menopausal women, seeking treatment for different ailments
      at a tertiary care, multidisciplinary hospital in Delhi, India, were examined for
      their vitamin D(3), quantified by 25-hydroxvitamin D (25-OH-D) level. Using a
      direct ELISA kit, the 25-OH-D levels were measured and were found to be
      sufficient in 30 (23.8%) cases, adequate in 10 cases (7.9%) and deficient in 86
      cases (68.2%). Severe hypo-vitaminosis in menopausal women in the Indian
      subcontinent ought to be treated with oral or parenteral supplementation. Point
      of-care assay formats are needed for quantification of 25-OH-D levels at
      healthcare centers.

PMID- 21879831
TI  - The StepOne real-time polymerase chain reaction detection of Salmonella sp.,
      Salmonella enterica ser. typhimurium and enteritidis in milk and meat.
AB  - The aim of this study was to follow contamination of ready to eat milk and meat
      products with Salmonella spp. by using the StepOne real-time polymerase chain
      reaction (PCR). Classical microbiological methods for detection of foodborne
      bacteria involve the use of pre-enrichment and/or specific enrichment, following
      isolation of bacteria in solid media and the final confirmation by biochemical
      and/or serological tests. We used the PrepSEQ Rapid Spin Sample Preparation Kit
      for isolation of DNA and MicroSEQ(r) Salmonella spp. Detection Kit for pursuance
      of the real-time PCR (Applied Biosystems). In samples without incubation we
      detected strain of Salmonella sp. in 5 out of 25 samples (swabs), as well as in
      the internal positive control (IPC), which was positive in all samples. This
      StepOne real-time PCR assay is extremely useful for any laboratory equipped by
      real-time PCR. It is a fast, reproducible, simple, specific and sensitive way to
      detect nucleic acids, which could be used in clinical diagnostic tests in the
      future. Our results indicated that real-time PCR assay developed in this study
      could sensitively detect Salmonella spp. in ready-to-eat food. This could prevent
      infection caused by Salmonella, and also could benefit food manufacturing
      companies by extending their product's shelf-life as well as saving the cost of
      warehousing their food products while awaiting pathogen testing results.

PMID- 21879832
TI  - Alternative antimicrobial compounds to control potential Lactobacillus
      contamination in bioethanol fermentations.
AB  - Antibiotics are commonly used to control microbial contaminants in yeast-based
      bioethanol fermentation. Given the increase in antibiotic-resistant bacteria,
      alternative natural antimicrobials were evaluated against the potential
      contaminant, Lactobacillus. The effects of nisin, epsilon-polylysine, chitosan
      (CS) and lysozyme were screened against 5 Lactobacillus strains. A standard broth
      microdilution method was used in 96-well plates to assess the minimal inhibitory
      concentration (MIC). L. delbrueckii subsp lactis ATCC479 exhibited maximal MICs
      with CS, epsilon-polylysine and nisin (1.87, 0.3125 and 0.05 mg/mL,
      respectively). Nisin reduced most Lactobacillus strains by 6 log CFU/mL after 48
      hours with the exception of L. casei. Synergism occurred when
      ethylenediaminetetraacetic acid (EDTA) was added with nisin. An MIC of 0.4 mg/mL
      of nisin combined with the EDTA at an MIC of 1 mg/ml markedly suppressed L .casei
      by 6 log CFU/mL. In conclusion, alternative antimicrobials proved to be a
      potential candidate for controlling bacterial contamination in the fermentation
      process. Synergistic effect of nisin with EDTA successfully inhibited the nisin
      resistant contaminant, L. casei.

PMID- 21879833
TI  - Lava cave microbial communities within mats and secondary mineral deposits:
      implications for life detection on other planets.
AB  - Lava caves contain a wealth of yellow, white, pink, tan, and gold-colored
      microbial mats; but in addition to these clearly biological mats, there are many
      secondary mineral deposits that are nonbiological in appearance. Secondary
      mineral deposits examined include an amorphous copper-silicate deposit (Hawai'i)
      that is blue-green in color and contains reticulated and fuzzy filament
      morphologies. In the Azores, lava tubes contain iron-oxide formations, a soft
      ooze-like coating, and pink hexagons on basaltic glass, while gold-colored
      deposits are found in lava caves in New Mexico and Hawai'i. A combination of
      scanning electron microscopy (SEM) and molecular techniques was used to analyze
      these communities. Molecular analyses of the microbial mats and secondary mineral
      deposits revealed a community that contains 14 phyla of bacteria across three
      locations: the Azores, New Mexico, and Hawai'i. Similarities exist between
      bacterial phyla found in microbial mats and secondary minerals, but marked
      differences also occur, such as the lack of Actinobacteria in two-thirds of the
      secondary mineral deposits. The discovery that such deposits contain abundant
      life can help guide our detection of life on extraterrestrial bodies.

PMID- 21879834
TI  - Patients' perceptions of services and preferences for care in amyotrophic lateral
      sclerosis: a review.
AB  - Service providers and service users often have different perspectives on health
      and social care services. We have undertaken a systematic review of empirical
      data between 1988 and March 2011 relating to ALS service users' perspectives on
      health and social care services. Forty-seven texts were extracted and a narrative
      synthesis conducted. Few studies have explored ALS patients' experiences in
      relation to their satisfaction with services. Our review showed that ALS patients
      expect dignified care but they are often dissatisfied with health care services
      and have unmet expectations of their care. Most studies of decision-making and
      preferences for care have focused on end-of-life intervention. Various factors
      influence preferences for care from the service user perspective and people with
      ALS may adjust their use of services as they negotiate change. In conclusion,
      further research on the timeliness of services to meet changing needs of service
      users is required. The service user experience of allied health care services
      prior to end-of-life care also warrants investigation. Service providers need to
      support people with ALS as they negotiate feelings of acceptance and
      independence. Research to identify the key parameters of the ALS patient
      experience of services is required.

PMID- 21879835
TI  - Adrenal lesions in patients with extra-adrenal malignancy - benign or malignant?
AB  - BACKGROUND: Adrenal lesions in patients with extra-adrenal malignancy can be part
      of disseminated tumour disease, but may also be incidental, benign finding.
      Strict characterisation is therefore crucial, and may have profound effects on
      patient management. PURPOSE: To prospectively characterise and follow-up adrenal
      lesions in patients with extra-adrenal malignancy, stratified into those with
      past or concurrent malignancy, with or without metastases. MATERIAL AND METHODS:
      All incidentally detected adrenal lesions identified at cross-sectional imaging
      during 18 months in a defined geographical region were prospectively reported.
      All adult oncologic patients with adrenal lesions were subjected to biochemical
      work-up and dedicated adrenal imaging for lesion characterisation, including a
      two year follow-up. RESULTS: Benign adrenal lesions were found in 74% (29/39) of
      patients who had a history of extra-adrenal malignancy, in 53% (57/108) of those
      with concurrent extra-adrenal malignancy without metastatic disease and in 25%
      (27/109) in those with signs of metastatic disease. CONCLUSION: An adrenal lesion
      occurring in a patient with past malignancy has a high likelihood of representing
      a benign lesion, and even in patients with present signs of malignant disease at
      least one fourth to one half of such lesions are benign. Dedicated adrenal
      imaging including computed tomography attenuation measurements with wash-out
      characteristics, in addition to biochemical testing for adrenal dysfunction, is
      highly recommended in these cases, especially in patients without any other signs
      of metastatic spread.

PMID- 21879836
TI  - A household survey on the extent of home medication storage. A cross-sectional
      study from rural Crete, Greece.
AB  - BACKGROUND: Patients often have multiple chronic diseases, use multiple
      prescriptions and over the counter medications resulting in polypharmacy. Many of
      them store these medications for future use in their homes, rather than take them
      as directed by their physician, resulting in a waste of health care resources,
      and potentially dangerous misuse. OBJECTIVES: This study aimed to investigate the
      magnitude of medication home hoarding, the exchange of medication with
      family/friends, families' beliefs about the medication use, source of medication,
      pharmaceutical class, cost of stored medicine and conditions of storage. METHODS:
      A structured questionnaire was administered within the homes in two rural areas
      in Crete. RESULTS: Forty families participated in the study including 85
      individual household members (36 men, and 49 women with an average age of 56.5 +/
      24.3 mean +/- SD). There were a total of 557 medications recorded, with 324
      different medications representing a total value of ?8954. The mean quantity of
      medication boxes stored in each home was 8.5 +/- 5.8. Cardiovascular medications
      accounted for 56% of medications for current use; whereas analgesics (24%), and
      antibiotics (17%), were the most medications being stored for future use.
      Exchange of medicine was very common (95%). Beliefs that 'more expensive
      medication is more effective', and that 'over the counter medications are safe
      because they were easily available' were expressed. CONCLUSIONS: Medications are
      being stored in large quantities in these rural areas, with a large percentage of
      them being wasted or misused.

PMID- 21879837
TI  - Drugs for neglected diseases: part II.

PMID- 21879838
TI  - The importance of patent sharing in neglected disease drug discovery.

PMID- 21879840
TI  - Interview with Solomon Nwaka.
AB  - Solomon Nwaka was born in Nigeria and grew up seeing at first hand the impact of
      neglected diseases. His research efforts have taken him across the globe, in both
      the developed and developing world. Following posts in academia, industry and at
      the Medicines for Malaria Venture, he is now at the WHO where he is engaged in
      initiating schemes to support research into neglected diseases in developing
      countries, notably the African Network for Drugs and Diagnostics Innovation,
      which is now an organization under the United Nations Economic Commission for
      Africa. He speaks to Future Medicinal Chemistry about what inspired him to take
      up a career in neglected disease research and how the developing world should
      lead the effort to tackle some of the diseases that most affect them.

PMID- 21879841
TI  - Diarylquinolines, synthesis pathways and quantitative structure--activity
      relationship studies leading to the discovery of TMC207.
AB  - The emergence of multidrug-resistant strains of Mycobacterium tuberculosis and
      resistance to current anti-TB drugs call for the discovery and development of new
      effective anti-TB drugs. TMC207 is the lead candidate of a novel class of
      antimycobacterial agents, the diarylquinolines, which specifically inhibit
      mycobacterial ATP synthase and displays high activity against both drug
      susceptible and multidrug-resistant strains of Mycobacterium tuberculosis. This
      article covers both synthesis pathways as well as qualitative and quantitative
      analyses of the structure-activity relationships of the diarylquinoline series on
      Mycobacterium smegmatis activity.

PMID- 21879842
TI  - Drugs for Neglected Diseases initiative model of drug development for neglected
      diseases: current status and future challenges.
AB  - The Drugs for Neglected Diseases initiative (DNDi) is a patients' needs-driven
      organization committed to the development of new treatments for neglected
      diseases. Created in 2003, DNDi has delivered four improved treatments for
      malaria, sleeping sickness and visceral leishmaniasis. A main DNDi challenge is
      to build a solid R&D portfolio for neglected diseases and to deliver preclinical
      candidates in a timely manner using an original model based on partnership. To
      address this challenge DNDi has remodeled its discovery activities from a project
      based academic-bound network to a fully integrated process-oriented platform in
      close collaboration with pharmaceutical companies. This discovery platform relies
      on dedicated screening capacity and lead-optimization consortia supported by a
      pragmatic, structured and pharmaceutical-focused compound sourcing strategy.

PMID- 21879843
TI  - Challenges and opportunities in developing novel drugs for TB.
AB  - Mycobacterium tuberculosis is a difficult pathogen to combat and the first-line
      drugs currently in use are 40-60 years old. The need for new TB drugs is urgent,
      but the time to identify, develop and ultimately advance new drug regimens onto
      the market has been excruciatingly slow. On the other hand, the drugs currently
      in clinical development, and the recent gains in knowledge of the pathogen and
      the disease itself give us hope for finding new drug targets and new drug leads.
      In this article we highlight the unique biology of the pathogen and several
      possible ways to identify new TB chemical leads. The Global Alliance for TB Drug
      Development (TB Alliance) is a not-for-profit organization whose mission is to
      accelerate the discovery and development of new TB drugs. The organization
      carries out research and development in collaboration with many academic
      laboratories and pharmaceutical companies around the world. In this perspective
      we will focus on the early discovery phases of drug development and try to
      provide snapshots of both the current status and future prospects.

PMID- 21879844
TI  - Challenges in antimalarial drug discovery.
AB  - Malaria is one of the most devastating diseases in the world, affecting almost
      225 million people a year, and causing over 780,000 deaths, most of which are
      children under the age of 5 years. Following the recent call for the eradication
      of the disease, supported by the WHO, there has been increasing investment into
      antimalarial drug-discovery projects. These activities are aimed at generating
      the next generation of molecules focused on the treatment and transmission
      blocking of Plasmodium falciparum and Plasmodium vivax endo- and exo-erythrocytic
      stages of the parasite. This article summarizes the current top-level thinking
      regarding the prosecution of such endeavors and the disease-specific
      considerations in project planning.

PMID- 21879845
TI  - Drug repositioning in the treatment of malaria and TB.
AB  - The emergence and spread of drug resistance in the malaria parasite Plasmodium
      falciparum as well as multi- and extremely drug-resistant forms of Mycobacterium
      tuberculosis, the causative agent of TB, could hamper the control of these
      diseases. For instance, there are indications that the malaria parasite is
      becoming resistant to artemisinin derivatives, drugs that form the backbone of
      antimalarial combination therapy. Likewise, Mycobacterium tuberculosis strains
      that are multidrug-resistant or extremely drug-resistant to first- and second
      line drugs have been associated with increased mortality. Thus, more than ever,
      new antimalarials and anti-TB drugs are needed. One of the strategies to discover
      new drugs is to reposition or repurpose existing drugs, thus reducing the cost
      and time of drug development. In this review, we discuss how this concept has
      been used in the past to discover antimalarial and anti-TB drugs, and summarize
      strategies that can lead to the discovery and development of new drugs.

PMID- 21879848
TI  - Foreword. Special issue: adverse effects of arsenic (As) on the environment.

PMID- 21879846
TI  - Nitroimidazoles for the treatment of TB: past, present and future.
AB  - Tuberculosis remains a leading cause of death resulting from an infectious agent,
      and the spread of multi- and extensively drug-resistant strains of Mycobacterium
      tuberculosis poses a threat to management of global health. New drugs that
      effectively shorten the duration of treatment and are active against drug
      resistant strains of this pathogen are urgently required to develop effective
      chemotherapies to combat this disease. Two nitroimidazoles, PA-824 and OPC-67683,
      are currently in Phase II clinical trials for the treatment of TB and the outcome
      of these may determine the future directions of drug development for anti
      tubercular nitroimidazoles. In this review we summarize the development of these
      nitroimidazoles and alternative analogs in these series that may offer attractive
      alternatives to PA-824 and OPC-67683 for further development in the drug
      discovery pipeline. Lastly, the potential pitfalls in the development of
      nitroimidazoles as drugs for TB are discussed.

PMID- 21879849
TI  - Arsenic-enriched groundwaters of India, Bangladesh and Taiwan--comparison of
      hydrochemical characteristics and mobility constraints.
AB  - Arsenic (As) enrichment in groundwater has become a major global environmental
      disaster. Groundwater samples were collected from 64 sites located in the
      districts of 24-Parganas (S), and Nadia in West Bengal, India (Bhagirathi sub
      basin), and 51 sites located in the districts of Comilla, Noakhali, Magura,
      Brahman baria, Laxmipur, Munshiganj, Faridpur and Jhenaida in Bangladesh (Padma
      Meghna sub-basin). Groundwater samples were also collected from two As-affected
      areas (Chianan and Lanyang plains) of Taiwan (n = 26). The concentrations of
      major solutes in groundwater of the Padma-Meghna sub-basin are more variable than
      the Bhagirathi sub-basin, suggesting variations in the depositional and
      hydrological settings. Arsenic concentrations in groundwaters of the studied
      areas showed large variations, with mean As concentrations of 125 MUg/L (range:
      0.20 to 1,301 MUg/L) in Bhagirathi sub-basin, 145 MUg/L (range: 0.20 to 891
      MUg/L) in Padma-Meghna sub-basin, 209 MUg/L (range: 1.3 to 575 MUg/L) in Chianan
      plain, and 102 MUg/L (range: 2.5 to 348 MUg/L) in Lanyang plain groundwater. The
      concentrations of Fe, and Mn are also highly variable, and are mostly above the
      WHO-recommended guideline values and local (Indian and Bangladeshi) drinking
      water standard. Piper plot shows that groundwaters of both Bhagirathi and Padma
      Meghna sub-basins are of Ca-HCO(3) type. The Chianan plain groundwaters are of Na
      Cl type, suggesting seawater intrusion, whereas Lanyang plain groundwaters are
      mostly of Na-HCO(3) type. The study shows that reductive dissolution of Fe(III)
      oxyhydroxides is the dominant geochemical process releasing As from sediment to
      groundwater in all studied areas.

PMID- 21879851
TI  - Application of geostatistics with Indicator Kriging for analyzing spatial
      variability of groundwater arsenic concentrations in Southwest Bangladesh.
AB  - This article seeks to explore the spatial variability of groundwater arsenic (As)
      concentrations in Southwestern Bangladesh. Facts about spatial pattern of As are
      important to understand the complex processes of As concentrations and its
      spatial predictions in the unsampled areas of the study site. The relevant As
      data for this study were collected from Southwest Bangladesh and were analyzed
      with Flow Injection Hydride Generation Atomic Absorption Spectrometry (FI-HG
      AAS). A geostatistical analysis with Indicator Kriging (IK) was employed to
      investigate the regionalized variation of As concentration. The IK prediction map
      shows a highly uneven spatial pattern of arsenic concentrations. The safe zones
      are mainly concentrated in the north, central and south part of the study area in
      a scattered manner, while the contamination zones are found to be concentrated in
      the west and northeast parts of the study area. The southwest part of the study
      area is contaminated with a highly irregular pattern. A Generalized Linear Model
      (GLM) was also used to investigate the relationship between As concentrations and
      aquifer depths. A negligible negative correlation between aquifer depth and
      arsenic concentrations was found in the study area. The fitted value with 95 %
      confidence interval shows a decreasing tendency of arsenic concentrations with
      the increase of aquifer depth. The adjusted mean smoothed lowess curve with a
      bandwidth of 0.8 shows an increasing trend of arsenic concentration up to a depth
      of 75 m, with some erratic fluctuations and regional variations at the depth
      between 30 m and 60 m. The borehole lithology was considered to analyze and map
      the pattern of As variability with aquifer depths. The study has performed an
      investigation of spatial pattern and variation of As concentrations.

PMID- 21879850
TI  - Temporal and seasonal variability of arsenic in drinking water wells in Matlab,
      southeastern Bangladesh: a preliminary evaluation on the basis of a 4 year study.
AB  - Temporal and seasonal variability of As concentrations in groundwater were
      evaluated in As-affected areas of Matlab, southeastern Bangladesh. Groundwater
      samples from 61 randomly selected tubewells were analyzed for As concentrations
      over a period of three years and four months (from July 2002 to November 2005)
      and monitored seasonally (three times a year). The mean As concentrations in the
      sampled tubewells decreased from 153 to 123 MUg/L during July 2002 to November
      2005. Such changes were pronounced in tubewells with As concentration >50 MUg/L
      than those with As concentrations <50 MUg/L. Similarly, individual wells revealed
      temporal variability, for example some wells indicated a decreasing trend, while
      some other wells indicated stable As concentration during the monitoring period.
      The mean As concentrations were significantly higher in Matlab North compared
      with Matlab South. The spatial variations in the mean As concentrations may be
      due to the differences in local geological conditions and groundwater flow
      patterns. The variations in mean As concentrations were also observed in shallow
      (<40 m) and deep (>40 m) wells. However, to adequately evaluate temporal and
      seasonal variability of As concentration, it is imperative to monitor As
      concentrations in tubewells over a longer period of time. Such long-term
      monitoring will provide important information for the assessment of human health
      risk and the sustainability of safe drinking water supplies.

PMID- 21879852
TI  - Natural contamination with arsenic and other trace elements in groundwater of the
      Central-West region of Chaco, Argentina.
AB  - This study covered the central agricultural region of the Chaco province, which
      lacks a permanent river networks. However, during the rainy period there is
      localized groundwater recharge. About 84 groundwater samples were taken during
      the period April-December 2007. These groundwater samples were collected from two
      different depths: 62 samples from shallow wells (4 to 20 m) and 24 samples from
      deep wells (20 to 100 m). Chemical variables were determined: pH, specific
      conductance, total dissolved solid, hardness, alkalinity, HCO(3)-, CO(3)(2-),
      SO(4)(2-), Cl-, NO(3)-, NO(2) -, NH(4)+, F-, As((tot)), Na+, K+, Ca2+, Mg2+, Fe,
      Cu, Ni, Pb and Zn. The chemical composition of groundwater in the study area is
      dominantly sodium bicarbonate and sodium chloride bicarbonate, comprising more
      than 60% (52/86) of shallow and deep groundwater samples. Of the 86 analyzed
      groundwater samples, 88% exceeded the WHO (World Health Organization) and CAA
      (Codigo Alimentario Argentino) standards (10 MUg/L) for As (arsenic) and 9%
      exceeded the WHO standard (1.5 mg/L) for F(-).Groundwater highly contaminated
      with As (max. 1,073 MUg/L) and F- (max. 4.2 mg/L) was found in shallow aquifer.
      The contaminated groundwater is characterized by high pH (max. 8.9), alkalinity
      (max. HCO(3)- 1,932 mg/L), SO(4)(2-) (max. 11,862 mg/L), Na(+) (max. 3,158 mg/L),
      Cl(-) (max. 10,493 mg/L) and electric conductivity greater than 33.3 MUS/cm.
      Other associated elements (Ni, Pb, Cu and Zn) are present in low concentrations,
      except for Fe that in 32% of samples exceeded the guideline value of 0.3 mg/L
      suggested by the CAA.

PMID- 21879853
TI  - Biogeochemical characteristics of Kuan-Tzu-Ling, Chung-Lun and Bao-Lai hot
      springs in southern Taiwan.
AB  - Hot springs are the important natural sources of geothermally heated groundwater
      from the Earth's crust. Kuan-Tzu-Ling (KTL), Chung-Lun (CL) and Bao-Lai (BL) are
      well-known hot springs in southern Taiwan. Fluid and mud (sediments) samples were
      collected from the eruption points of three hot springs for detailed
      biogeochemical characterization. The fluid sample displays relatively high
      concentrations of Na(+) and Cl(-) compared with K(+), Mg(2+), Ca(2+), NO(2) (-),
      and SO(4) (2-), suggesting a possible marine origin. The concentrations of Fe,
      Cr, Mn, Ni, V and Zn were significantly higher in the mud sediments compared with
      fluids, whereas high concentrations of As, Ba, Cu, Se, Sr and Rb were observed in
      the fluids. This suggests that electronegative elements were released during
      sediment-water interactions. High As concentration in the fluids was observed to
      be associated with low redox (Eh) conditions. The FTIR spectra of the humic acid
      fractions of the sediments showed the presence of possible functional groups of
      secondary amines, ureas, urethanesm (amide), and silicon. The sulfate-reducing
      deltaproteobacterium 99% similar to Desulfovibrio psychrotolerans (GU329907) were
      rich in the CL hot spring while mesophilic, proteolytic, thiosulfate- and sulfur
      reducing bacterium that 99% similar to Clostridium sulfidigenes (GU329908) were
      rich in the BL hot spring.

PMID- 21879854
TI  - Biogeochemical interactions among the arsenic, iron, humic substances, and
      microbes in mud volcanoes in southern Taiwan.
AB  - Fluid and mud samples collected from Hsiaokunshui (HKS), Wushanting (WST),
      Yenshuikeng (YSK), Kunshuiping (KSP), Liyushan (LYS), and Sinyangnyuhu (SYNH) mud
      volcanoes of southwestern Taiwan were characterized for major ions, humic
      substances (HS) and trace elements concentrations. The relationship between the
      release of arsenic (As) and activities of sulfate-reducing bacteria has been
      assessed to understand relevant geochemical processes in the mud volcanoes.
      Arsenic (0.02-0.06 mg/L) and humic substances (4.13 * 10(-4) to 1.64 * 10(-3) mM)
      in the fluids of mud volcanoes showed a positive correlation (r = 0.99, p < 0.05)
      except in Liyushan mud volcano. Arsenic and iron in mud sediments formed two
      separate groups i) high As, but low Fe in HKS, WST, and SYNH; and ii) low As, but
      high Fe in the YSK, KSP, and LYS mud volcanoes. The Eh(S.H.E.) values of the mud
      volcano liquids were characterized by mild to strongly reducing conditions. The
      HKS, SYNH, and WST mud volcanoes (near the Chishan Fault) belongs to strong
      reducing environment (-33 to -116 mV), whereas the LYS, YSK, and KSP mud
      volcanoes located near the coastal plain are under mild reducing environment (-11
      to 172 mV). At low Eh values mud volcanoes, saturation index (SI) values of
      poorly crystalline phases such as amorphous ferric hydroxide indicate
      understaturation, whereas saturation is reached in relatively high Eh(S.H.E.)
      values mud volcanoes. Arsenic contents in sediments are low, presumably due to
      its release to fluids (As/Fe ratio in YSK, KSP, and LYS sediment: 4.86 * 10(-4)
      6.20 * 10(-4)). At low Eh(S.H.E.) values (mild to strong reducing environment),
      arsenic may co-precipitate with sulfides as a consequence of sulfate reduction
      (As/Fe ratios in WST, HKS, and SYNH sediments: 0.42-0.69).

PMID- 21879855
TI  - Role of organic matter and humic substances in the binding and mobility of
      arsenic in a Gangetic aquifer.
AB  - Arsenic (As) enrichment in groundwater has led to extensive research,
      particularly on the factors responsible for its release into groundwater. In the
      Gangetic plain, organic matter driven microbial reduction of Fe-oxyhydroxides is
      considered as the most plausible mechanism of As release into groundwater.
      However, the role of organic matter in the aqueous environment is not well known
      and particularly that of organometallic complex. In this study, we have
      characterized bulk sediment and groundwater samples, collected from Barasat, West
      Bengal, India, to understand the effect of organic matter in the binding and
      mobility of As in the subsurface environment. The results showed a moderate
      correlation (R(2) = 0.49, p < 0.05) between dissolved organic carbon (DOC) and As
      in groundwater, suggesting that DOC has a role in releasing As into groundwater.
      The relative fluorescent intensity (RFI) of the dissolved humic substances in
      groundwater showed a maximum value of 65 QSU (mean: 47 +/- 8 QSU). FT-IR spectra
      of the extracted humic acid fractions of the sediment showed COO-, C = O, OH, and
      C = C (aromatic ring) functional groups, which may act as a chelating agents with
      the metal(loid)s. FT-IR spectra of the HA-As complex exhibited specific peaks at
      1242 and 832 cm(-1) in the fingerprint region. This is similar to the extracted
      humic acid fractions of the Gangetic sediment, suggesting binding of As with
      humic substances.

PMID- 21879856
TI  - The potential for reductive mobilization of arsenic [As(V) to As(III)] by OSBH(2)
      (Pseudomonas stutzeri) and OSBH(5) (Bacillus cereus) in an oil-contaminated site.
AB  - Microbial reduction of arsenate [As(V)] plays an important role in arsenic (As)
      mobilization in aqueous environments. In this study, we investigated reduction of
      arsenate by different bacterial isolates such as OSBH(1) (GU329913), OSBH(2)
      (GU329914), OSBH(3) (GU329915), OSBH(4) (GU329916) and OSBH(5) (GU329917),
      isolated from the oil sludge of a sewage treatment plant operated by the China
      Petroleum Refinery Company in Kaohsiung, southern Taiwan. Bacterial strains of
      pure culture were identified by 16S rRNA analysis (>=99 % nucleotide similarity).
      Morphological and 16S rRNA analysis show that the isolate OSBH(1) is similar to
      E. coli, OSBH(2) is similar to P. stutzeri, OSBH(3) is similar to P. putida,
      OSBH(4) is similar to P. aeruginosa, and OSBH(5) is similar to B. Cereus. The
      As(V) was transformed to As(III) in the presence of isolates OSBH(2) and OSBH(5)
      by a detoxification process. The potential reduction rates of As(V) were higher
      in the presence of isolate OSBH(5) compared to the isolate OSBH(2). The microbial
      growth (cell/mL) of isolate OSBH(5) was significantly higher in culture medium
      compared to OSBH(2). The bacterial isolates such as OSBH(1), OSBH(3) and OSBH(4)
      were found to be incapable of transforming the As(V). It is concluded that the
      activity of the oil-degrading bacterial isolates described in this work
      contributes to the mobilization of As in the more toxic As(III) form that affects
      biotic life.

PMID- 21879857
TI  - Fractionation and bioavailability of arsenic in agricultural soils: solvent
      extraction tests and their relevance in risk assessment.
AB  - Sequential extraction procedure (SEP) and a physiologically based extraction test
      (PBET) were performed with the aim to estimate the mobility, bioavailability (for
      plants and humans) and spatial variation of arsenic in agricultural soils in the
      Valleys of Arica and Parinacota Region (Northern Chile). For this purpose, 50
      topsoil samples with different total arsenic contents in soil (36.2-729 mg kg(
      1)) were collected from 10 selected sites in the Valley of Lluta, Azapa and
      Camarones. The SEP test results showed that arsenic was mainly associated to the
      least mobile fractions: bound to amorphous and poorly crystalline hydrous oxides
      of Fe and Al (11.6-44.2%) and well-crystallized hydrous oxides of Fe and Al (24.8
      48.9%). Calculated values for arsenic Chronic Daily Intake (CDI), based on the
      information obtained in the tests of bioaccessibility using PBET (range 1.6-9.6
      mg kg(-1)), were in the range of 0.021 to 0.128 MUg As kg(-1) d(-1), not
      exceeding in any case the maximum Reference Dose for Chronic Oral Exposure, RfD =
      0.3 MUg kg(-1) d(-1), established by USEPA. In general, obtained results, allow
      us to establish that extraction processes using solvents can be utilized as a
      source of reliable and useful information for risk assessment of exposure to
      arsenic from soil, over the direct use of total arsenic contents, which can lead
      to an overestimation of the toxicity by direct ingestion.

PMID- 21879858
TI  - Human exposure to arsenic through foodstuffs cultivated using arsenic
      contaminated groundwater in areas of West Bengal, India.
AB  - The widespread incidence of chronic arsenicosis in the Bengal Delta has led to
      intensive research on arsenic (As) enrichment in groundwater as well as
      accumulation in foodstuffs, as there are potential health risks associated with
      exposure to As from both sources. This study deals with human As exposure through
      the drinking of groundwater, consumption of locally grown foodstuffs (e.g., crops
      and vegetables) and cooked food in Nadia district, West Bengal. Groundwater and
      foodstuffs were collected and analyzed with FI-HG-AAS to estimate the total As
      content. Urine samples collected from human subjects were analyzed to assess the
      As exposure. Two major crops, boro and aman rice, showed a considerable amount of
      As, with mean values of 194 and 156 MUg kg(-1), respectively. Significant levels
      of As were also found in other common crops and vegetables cultivated in this
      area (for example, the mean As in Arum and radish was 780 and 674 MUg kg(-1),
      respectively). Total intake of As from foodstuffs by adults (560 MUg day(-1)) and
      children (393 MUg day(-1)) in the area was found to be at alarming levels.
      Arsenic exposure was demonstrated by the presence of As in urine (ranging between
      154 and 276 MUg L(-1)), with overall As retention of 50-60 %. The results of this
      study further indicate the potential risk of As exposure to local inhabitants
      through the food chain which is associated with continuous consumption of As
      contaminated foodstuffs. Therefore, more action needs to be taken to control the
      contamination pathways (such as the water-soil-crop system) to protect humans
      from continuous ingestion of As through foodstuffs.

PMID- 21879859
TI  - Health risks for human intake of aquacultural fish: Arsenic bioaccumulation and
      contamination.
AB  - Aquacultural tilapia (Oreochromis mossambicus L.) and shrimp (Penaeus monodon L.)
      from groundwater-cultured ponds in southwestern Taiwan were analyzed to estimate
      arsenic (As) bioaccumulation and the potential health risk to human intake. Most
      of aquacultural ponds exhibited higher arsenic than maximum allowed
      concentrations (50 MUg L(-1)) in pond water of Taiwan. Arsenic levels in tilapia
      in Budai, Yichu and Beimen were 0.92 +/- 0.52 MUg g(-1), 0.93 +/- 0.19 MUg g(-1)
      and 0.76 +/- 0.03 MUg g(-1), respectively and in shrimp was 0.36 +/- 0.01 MUg g(
      1) in Beimen. Total arsenic in tilapia is highly correlated (R(2) = 0.80) with
      total arsenic concentration of pond water. Total arsenic in fish showed high
      correlation with that in bone (R(2) = 0.98), head (R(2) = 0.97) and tissue (R(2)
      = 0.96). Organic arsenic species (DMA) was found higher relative to inorganic
      species of As(III) and As(V). The average percent contribution of inorganic
      arsenic to total arsenic in fish samples was 12.5% and ranged between 11.7 to
      14.2%. Bioaccumulation factors (BAFs) for total arsenic in fish ranged from 10.3
      to 22.1, whereas BAF for inorganic arsenic ranged from 1.33 to 2.82. The mean
      human health cancer risk associated with the ingestion of inorganic arsenic in
      the fish was estimated at 2.36 * 10(-4) +/- 0.99 * 10(-4), which is over 200
      times greater than a de Minimus cancer risk of 1 * 10(-6). The mean human health
      hazard quotient associated with ingesting inorganic arsenic in the fish was 1.22
      +/- 0.52, indicating that expected human exposure exceeds the reference dose for
      non-cancer health effects by 22%. These results suggest that the inhabitants in
      this region are being subjected to moderately elevated arsenic exposure through
      the consumption of tilapia and shrimp raised in aquaculture ponds.

PMID- 21879860
TI  - Levels of total arsenic in edible fish and shellfish obtained from two coastal
      sectors of the Atacama Desert in the north of Chile: use of non-migratory marine
      species as bioindicators of sea environmental pollution.
AB  - The Camarones (CB) and Vitor (VB) Bays are situated in the middle of Atacama
      Desert, and their economies are based on activities entirely associated with the
      extraction of marine produce. The aim of this study was to determine the total
      arsenic content in three species of fish and seven species of shellfish from
      these two bays. The quantification of the total arsenic content in these products
      was performed by Hydride-Generation Atomic Absorption Spectrometry, HG-AAS. The
      results showed that marine species associated with the CB sector had higher total
      arsenic levels than the same species in the area of VB, a finding attributed to
      much higher total arsenic concentrations in the water and soils of CB than VB.
      The species with the highest total arsenic concentration was the Venus antique
      (7.50 mg kg (-1)) from the CB, and the lowest total arsenic content was found in
      Cheilodactylidae variegatus (0.34 mg kg(-1)) from VB.

PMID- 21879861
TI  - Arsenic in freshwater fish in the Chihuahua County water reservoirs (Mexico).
AB  - Water reservoirs in Chihuahua County, Mexico, are affected by some punctual and
      non-punctual geogenic and anthropogenic pollution sources; fish are located at
      the top of the food chain and are good indicators for the ecosystems pollution.
      The study goal was to: (i) determine arsenic concentration in fish collected from
      the Chuviscar, Chihuahua, San Marcos and El Rejon water reservoirs; (ii) to
      assess if the fishes are suitable for human consumption and (iii) link the
      arsenic contents in fish with those in sediment and water reported in studies
      made the same year for these water reservoirs. Sampling was done in summer, fall
      and winter. The highest arsenic concentration in the species varied through the
      sampling periods: Channel catfish (Ictalurus punctatus) with 0.22 +/- 0.15 mg/kg
      dw in winter and Green sunfish (Lepomis cyanellus) with 2.00 +/- 0.15 mg/kg dw in
      summer in El Rejon water reservoir. A positive correlation of arsenic contents
      was found through all sampling seasons in fish samples and the samples of
      sediment and water. The contribution of the weekly intake of inorganic arsenic,
      based on the consumption of 0.245 kg fish muscles/body weight/week was found
      lower than the acceptable weekly intake of 0.015 mg/kg/body weight for inorganic
      arsenic suggested by FAO/WHO.

PMID- 21879862
TI  - Simultaneous removal of arsenic and fluoride from groundwater by coagulation
      adsorption with polyaluminum chloride.
AB  - The ArCIS-UNR(r) arsenic and fluoride removal system which consists of a
      coagulation-adsorption process with initial pH adjustment and two filtration
      stages (up-flow gravel roughing filtration and rapid filtration), has been
      already described in previous studies. This process has been successfully
      implemented in full-scale plants in Argentina, with fluoride and total arsenic
      concentrations in raw water up to 2 mg/L and 200 MUg/L, respectively. The aim of
      the present study is to optimize fluoride removal when it is >2.0 mg/L. The
      modifications proposed were to decrease the pH level to 6.4-6.6 at the roughing
      filter inlet and increase the pH level to 7.2-7.6 at the rapid filter inlet to
      decrease residual aluminum concentration. Laboratory and pilot scale studies were
      performed using natural water with fluoride concentrations ranging from 2.4 to
      3.2 mg/L and arsenic concentrations from 60 to 90 MUg/L. An optimal combination
      of operational parameters and the coagulant dose (polyaluminum chloride, PACl)
      was found, to achieve final concentrations of fluoride, arsenic and aluminum in
      treated water lower than those set by the regulations in force. Filtration run
      time was 10 to 12 hours; research studies are necessary to extend this period.

PMID- 21879863
TI  - Arsenic removal from groundwater of the Chaco-Pampean plain (Argentina) using
      natural geological materials as adsorbents.
AB  - Use of natural geological materials for arsenic (As) removal is an emerging
      solution at a household level for poor people in remote rural settlements,
      especially when the materials are locally available and can be collected by the
      local population. Their low or zero cost makes these materials very attractive
      compared with synthetic or commercial materials. Sometimes, this may be the only
      option to provide safe water to very poor settlements. Their suitability for As
      removal from water is mainly due to adsorption, co-precipitation and ion exchange
      processes involving Fe- and Al-rich minerals and clay minerals present in the
      soils or sediments. In the present study, various clay-rich soils from the
      Santiago del Estero province (SDE, NW Argentina) and, for comparison, a laterite
      from the Misiones province have been tested as adsorbents for As in shallow
      naturally contaminated groundwaters of the Rio Dulce alluvial aquifer in SDE.
      Batch adsorption experiments showed higher As(V) removal for the Misiones
      laterite sample (99 %) as compared with the soils from SDE (40-53 %), which can
      be related to lower contents of water-soluble and oxalate extractable Al and Fe
      in the last samples. These results suggest the application of the Misiones
      laterite soil as an alternative for As removal. However, high transportation
      costs from Misiones to SDE can be an economical restriction for the low-income
      population of SDE.

PMID- 21879864
TI  - Dangerous "spin": the probability myth of evidence-based prescribing - a Merleau
      Pontyian approach.
AB  - OBJECTIVE: The aim of this study was to examine logical positivist statistical
      probability statements used to support and justify "evidence-based" prescribing
      rules in psychiatry when viewed from the major philosophical theories of
      probability, and to propose "phenomenological probability" based on Maurice
      Merleau-Ponty's philosophy of "phenomenological positivism" as a better clinical
      and ethical basis for psychiatric prescribing. CONCLUSIONS: The logical
      positivist statistical probability statements which are currently used to support
      "evidence-based" prescribing rules in psychiatry have little clinical or ethical
      justification when subjected to critical analysis from any of the major theories
      of probability and represent dangerous "spin" because they necessarily exclude
      the individual , intersubjective and ambiguous meaning of mental illness. A
      concept of "phenomenological probability" founded on Merleau-Ponty's philosophy
      of "phenomenological positivism" overcomes the clinically destructive
      "objectivist" and "subjectivist" consequences of logical positivist statistical
      probability and allows psychopharmacological treatments to be appropriately
      integrated into psychiatric treatment.

PMID- 21879865
TI  - Formulation: a proposal for a more structured, longitudinal approach.
AB  - OBJECTIVE: The aim of this study was to consider formulation enabling a
      longitudinal perspective to improve the quality of clinical information. METHOD:
      An overview of RANZCP guidelines for formulation, our observations of formulation
      in practice, and consideration of the requirements of current clinical
      documentation systems were employed. RESULTS: A five paragraph structured
      approach to formulation, with an example, is proposed. CONCLUSION: A structured
      schema for longitudinal formulation offers advantages for mental health services
      working over time with consumers with severe and enduring illnesses and should be
      considered in the development of clinical information systems.

PMID- 21879866
TI  - Evaluating the utility of a bipolar self-test screening measure.
AB  - OBJECTIVE: To detail the methodology of an online study designed to test the
      utility of a bipolar self-test screening measure. METHOD: We describe the current
      technical success of an online methodology in recruiting a large sample with
      minimal cost. RESULTS: Over some six months, more than 120 000 people accessed
      the Black Dog Institute Bipolar Self-Test, with screening criteria allowing a
      cohort to be recruited. CONCLUSION: This paper details the overall study strategy
      that will be reported on after a large finite sample has been derived.

PMID- 21879867
TI  - Suicide in Old Norse and Finnish folk stories.
AB  - OBJECTIVE: The aim of this study was to examine the folk stories of Norway,
      Iceland and Finland with a view to discovering accounts of suicide as an escape
      option from intolerable predicaments, and to compare any such accounts with
      material from Southern Europe. METHOD: The Poetic Edda (Norway/Iceland) and The
      Kalevala (Finland) were examined for accounts of suicide, and evidence regarding
      the influence of these texts and individual accounts was collected. RESULTS: The
      Poetic Edda provided one account and The Kalevala three accounts of suicide
      performed as a means of escaping intolerable situations. Both the Poetic Edda and
      The Kalevala are in public awareness and have influenced the politics and culture
      of their respective regions. The individual suicides have been depicted in
      literature, music and the visual arts, from the distant past to the present time.
      CONCLUSION: Suicide as a means of escape from intolerable predicaments has been
      public knowledge in these regions for a millennium. This is consistent with
      findings from Southern Europe and substantiates that intolerable predicaments may
      lead to suicide.

PMID- 21879868
TI  - Adolescent admissions to adult psychiatric units: patterns and implications for
      service provision.
AB  - OBJECTIVE: The aim of this study was to investigate patterns of child and
      adolescent admissions to an acute adult psychiatric unit in a rural city.
      Correlates of admissions were then considered in terms of service reform for this
      vulnerable, under-resourced group. METHOD: The study reviewed consecutive
      clinical records of children and adolescents who were admitted to an acute
      general psychiatric inpatient unit over a 6 year period (N = 332). RESULTS:
      Patients generally experienced numerous pre-admission psychosocial stressors;
      there were many abuse histories and/or juvenile justice involvement. The
      principal diagnosis was varied and comorbidity was common. Maori patients were
      over-represented. The majority of admissions occurred out of working hours and
      more than half came from rural areas. There was high usage of the Mental Health
      Act on admission. Common causes of admission were self-harm and suicidal
      behaviour. The majority of the admitted adolescents required follow up by child
      and adolescent mental health services after discharge. CONCLUSION: We identified
      several reform possibilities, including up-skilling emergency and adult mental
      health staff in child and adolescent mental health, exploration of alternatives
      to admissions and specialist service coverage.

PMID- 21879869
TI  - Improving the care of mentally ill patients in a tertiary emergency department:
      development of a psychiatric assessment and planning unit.
AB  - OBJECTIVE: The aim was to describe the Psychiatric Assessment and Planning Unit
      (PAPU), established at the Royal Melbourne Hospital (RMH) to improve access to
      psychiatric care for patients presenting via the Emergency Department (ED).
      METHOD: PAPU was opened in January 2007. Data was recorded from RMH ED databases
      to compare ED lengths of stay (LOS) prior to and after establishing PAPU.
      Interventions including requirement for one-to-one nursing (i.e. one nurse
      dedicated to the care and observation of one patient) and mechanical restraint
      and unarmed security threats are routinely documented and were compared before
      and after PAPU opened. Demographic data and inpatient LOS information was
      collected by clinicians in PAPU. RESULTS: During the 12 months of initial
      evaluation we found that PAPU assisted with reducing the number of patients
      waiting excessive LOS in the RMH ED essentially to zero, due to both expedient
      transfers from ED and increased direct admissions from the community. We were
      also able to demonstrate a reduction in mechanical restraint, security codes for
      unarmed threats and one-to-one nursing in the ED. CONCLUSIONS: The establishment
      of the PAPU at RMH has resulted in significant improvement in the care of
      patients with mental illness in the least restrictive environment, based on
      decreased LOS and need for interventions.

PMID- 21879870
TI  - Building consumers in to service evaluation: development of the MH-CoPES
      Framework in New South Wales.
AB  - OBJECTIVE: The aim of this paper is to present the Mental Health Consumer
      Perceptions and Experiences of Services (MH-CoPES) Framework and discuss its
      development. The Framework was developed to address the need for a consistent
      approach across New South Wales mental health services for consumer involvement
      in service evaluation and planning. CONCLUSIONS: A four step Framework has been
      developed for implementation across adult public mental health services in NSW.
      The Framework focuses not only on collecting consumers' views of mental health
      services but on ensuring that procedures to report on and make changes based on
      this information are in place.

PMID- 21879871
TI  - The King's Speech: the stuttering puffs of royal transference.

PMID- 21879872
TI  - Monitoring in clozapine rechallenge after myocarditis.

PMID- 21879873
TI  - A blow to the temple.

PMID- 21879874
TI  - Undiagnosis.

PMID- 21879875
TI  - Core competencies of consumer consultants employed in Victorian mental health
      services.

PMID- 21879878
TI  - From the honorary secretary.

PMID- 21879877
TI  - From the president.

PMID- 21879879
TI  - From the chief executive officer.

PMID- 21879881
TI  - Stemming the tide.

PMID- 21879882
TI  - In vivo binding of Orc2 to a region of the chicken lysozyme GAS41 origin
      containing multiple Sp1-binding sites.
AB  - Most known DNA replication origins in vertebrate genomes have been found to occur
      close to transcriptional promoters. The origin of bidirectional DNA replication
      of the chicken lysozyme GAS41 locus was identified in a CpG island covering the
      GAS41 gene promoter. In this study, we generated an alpha-Orc2 antibody from
      rabbits immunized with the C-terminal half of Orc2 for studying in vivo Orc2
      binding to the lysozyme-GAS41 origin. Using the chromatin immunoprecipitation
      technique and quantitative real-time polymerase chain reaction, we were able to
      map the Orc2-binding site to a region of the lysozyme GAS41 origin that contains
      multiple Sp1/Sp3-binding sites co-mapping with two DNase I hypersensitive sites.
      Further, knockdown of endogenous Sp1 by RNA interference reduced specific Orc2
      binding to the lysozyme GAS41 origin. These results suggest that Sp1 participates
      in recruiting Orc2 to the origin.

PMID- 21879883
TI  - Risk factors for nonadherence with Pap testing in HIV-infected women.
AB  - BACKGROUND: HIV-infected women are at increased risk for cervical cancer; thus,
      adherence with Papanicolaou (Pap) testing is of particular importance. The
      objective of this study was to identify risk factors for inadequate Pap testing
      in a diverse cohort of HIV-infected women at a large urban safety net HIV clinic.
      METHODS: This retrospective cohort study assessed HIV-infected women aged 18?60
      years in care between October 1, 2003, and March 31, 2008, for risk factors for
      inadequate Pap testing. Unadjusted odds ratios (OR) with confidence intervals
      (CI) and multivariate analyses with generalized estimating equations for
      correlated data were calculated. RESULTS: Of 549 women, 293 (53.4%) had a Pap
      test during each follow-up period. Women who were older, white or Hispanic
      race/ethnicity, U.S. born, unemployed, drug users, and those with advanced HIV
      had increased odds of no Pap testing in unadjusted analyses. In multivariate
      analyses, U.S.-born women who were white or unemployed or had a baseline CD4
      count <200 cells/mm(3) had increased odds of no Pap testing (OR 2.0, 95% CI 1.3
      3.1; OR 2.3, CI 1.0-5.0; OR 1.7, CI 1.0-2.9, respectively). For non-U.S.-born
      women, age ?50 years (OR 3.9, CI 1.7-9.0), non-English-speaking status (OR 1.6,
      CI 1.0-2.4), and drug use (OR 5.8, CI 2.5-13.9) were associated with no Pap
      testing. CONCLUSIONS: U.S.-born status and low CD4 count were associated with
      increased odds of inadequate Pap testing. Further study is needed to identify
      interventions to improve Pap testing adherence in this high-risk group.

PMID- 21879884
TI  - Why is Facebook so successful? Psychophysiological measures describe a core flow
      state while using Facebook.
AB  - People are more and more using social networking sites (SNSs) like Facebook and
      MySpace to engage with others. The use of SNSs can have both positive and
      negative effect on the individual; however, the increasing use of SNSs might
      reveal that people look for SNSs because they have a positive experience when
      they use them. Few studies have tried to identify which particular aspects of the
      social networking experience make SNSs so successful. In this study we focus on
      the affective experience evoked by SNSs. In particular, we explore whether the
      use of SNSs elicits a specific psychophysiological pattern. Specifically, we
      recorded skin conductance, blood volume pulse, electroencephalogram,
      electromyography, respiratory activity, and pupil dilation in 30 healthy subjects
      during a 3-minute exposure to (a) a slide show of natural panoramas (relaxation
      condition), (b) the subject's personal Facebook account, and (c) a Stroop and
      mathematical task (stress condition). Statistical analysis of the
      psychophysiological data and pupil dilation indicates that the Facebook
      experience was significantly different from stress and relaxation on many linear
      and spectral indices of somatic activity. Moreover, the biological signals
      revealed that Facebook use can evoke a psychophysiological state characterized by
      high positive valence and high arousal (Core Flow State). These findings support
      the hypothesis that the successful spread of SNSs might be associated with a
      specific positive affective state experienced by users when they use their SNSs
      account.

PMID- 21879885
TI  - Cancer patients use hospital-based care until death: a further analysis of the
      Dutch Bone Metastasis Study.
AB  - PURPOSE: To describe health care utilization (HCU) at the end of life in cancer
      patients. These data are relevant to plan palliative care services, and to
      develop training programs for involved health care professionals. METHODS: The
      Dutch Bone Metastasis Study (DBMS) was a nationwide study proving equal
      effectiveness of single fraction palliative radiotherapy compared with multiple
      fractions for painful bone metastases in 1157 patients. The 860 (74%) patients
      who died during follow-up were included in the current analysis. The main outcome
      was the frequency of hospital-based (outpatient contact or admission) and/or
      general practitioner (GP) contact during the last 12 weeks of life. Changes in
      HCU towards death were related to data on quality of life and pain intensity
      using a multilevel regression model. RESULTS: Hospital-based HCU was reported in
      1801 (63%) returned questionnaires, whereas GP contact was stated in 1246 (43%).
      In 573 (20%) questionnaires, both types of HCU were reported. In multilevel
      regression analyses, the frequency of outpatient contacts remained constant
      during the weeks towards death, whereas the frequency of GP contacts increased.
      Lower valuation of quality of life was related to both GP- and hospital-based
      HCU. CONCLUSIONS: There was a high consumption of hospital-based HCU in the last
      12 weeks of life of cancer patients with bone metastases. Hospital-based HCU did
      not decrease during the weeks towards death, despite an increase in GP contacts.
      Future planning of palliative care and training programs should encompass close
      collaboration between medical specialists and GPs to optimize end-of-life care.

PMID- 21879886
TI  - Long-term outcomes of immediate versus delayed nephroureterectomy for upper tract
      urothelial carcinoma.
AB  - PURPOSE: To compare immediate nephroureterectomy with delayed nephroureterectomy
      after a trial of nephron-sparing endoscopic surgery in patients who were treated
      initially at our institution from 1996 to 2004 for upper tract urothelial
      carcinoma. Patients were monitored for upper tract recurrences, metastases,
      cancer-specific and overall survival. Survival outcomes and perioperative
      measurements were compared between treatment groups. RESULTS: Of 73 patients, 62
      underwent immediate nephroureterectomy and 11 proceeded to nephroureterectomy
      after failed endoscopic management. Mean follow-up for all patients was 58 months
      and 75 months for patients who were alive at last follow-up. Patients treated
      initially with endoscopy averaged a surveillance procedure every 3.7 months and
      had a median delay to nephroureterectomy of 10 months. Perioperative measurements
      at time of nephroureterectomy did not differ between groups. Overall survival 5
      years from initial resection in the delayed group and from nephroureterectomy in
      the immediate group was 64% and 59%, respectively; the corresponding 5-year
      cancer-specific and metastasis-free survival estimates were 91% vs 80% and 77% vs
      73%, respectively (P>0.05). Pathologic progression from low to high-grade
      occurred in three of seven patients from the delayed group. CONCLUSIONS: Failure
      of endoscopic management necessitating nephroureterectomy does not appear to
      affect survival outcomes compared with immediate nephroureterectomy in patients
      with upper tract urothelial carcinoma. A trial of endoscopic management can be
      considered in patients with low-grade disease and a normal contralateral kidney.
      Endoscopy is a viable option when there are imperative indications for nephron
      sparing in the setting of high-grade disease.

PMID- 21879887
TI  - Obtained mydriasis in long-term type 2 diabetic patients.
AB  - PURPOSE: The purpose of this study was to evaluate obtained mydriasis and
      prevalence of small pupil in long-term type 2 diabetic patients. METHODS: A
      prospective observational cross-sectional study was carried out. We included 107
      eyes from 107 patients (mean age: 60.8) with long-term (>=10 years) type 2
      diabetes mellitus. Patients were divided into 2 groups: no apparent diabetic
      retinopathy (group 1, n=33) and diabetic retinopathy (group 2, n=74). Exclusion
      criteria were eyes with prior intraocular surgeries, presence of other ocular
      disorders that may affect iris, or any other condition that precludes the precise
      measurement of pupil size. Sixty eyes in 60 age-matched nondiabetic patients
      (mean age: 61.0) scheduled for routine fundoscopy exam were enrolled as control.
      We measured pupil diameter by pupil gauges at 40 min after instillation of eye
      drops (phenylephrine 10% and tropicamide 1%). Small pupil was defined as pupil
      diameter of 6 mm or less. RESULTS: Mean pupil diameter was 8.07 mm [standard
      deviation (SD): 0.59 mm] in the control group, 7.46 mm (SD: 0.71 mm) in group 1,
      and 7.24 mm (SD: 0.83 mm) in group 2. Both group 1 (P<0.001) and group 2
      (P<0.001) showed significant difference when compared with the control group. The
      incidences of small pupil were 1.9% in the control group, 6.1% in group 1, and
      13.5% in group 2. When compared with control, group 2 showed significantly higher
      incidence of small pupil (P=0.023). CONCLUSIONS: Long-term diabetic patients
      showed poorer response to pharmacological mydriasis than nondiabetic patients.
      Higher prevalence of small pupil size was found in patients with diabetic
      retinopathy.

PMID- 21879888
TI  - Who owns federally funded research? The Supreme court and the Bayh-Dole act.

PMID- 21879889
TI  - Health care policy in an age of austerity.

PMID- 21879890
TI  - Fallback cuts or super-committee concoction--choosing health care's policy
      poison.

PMID- 21879891
TI  - Asthma phenotypes and interleukin-13--moving closer to personalized medicine.

PMID- 21879892
TI  - Improving care for dual eligibles through innovations in financing.

PMID- 21879893
TI  - Images in clinical medicine. Lung herniation after minimally invasive
      cardiothoracic surgery.

PMID- 21879894
TI  - Health technologies and innovation in the global health arena.

PMID- 21879895
TI  - The art of doing nothing.

PMID- 21879898
TI  - A functional element necessary for fetal hemoglobin silencing.
AB  - BACKGROUND: An improved understanding of the regulation of the fetal hemoglobin
      genes holds promise for the development of targeted therapeutic approaches for
      fetal hemoglobin induction in the beta-hemoglobinopathies. Although recent
      studies have uncovered trans-acting factors necessary for this regulation,
      limited insight has been gained into the cis-regulatory elements involved.
      METHODS: We identified three families with unusual patterns of hemoglobin
      expression, suggestive of deletions in the locus of the beta-globin gene (beta
      globin locus). We performed array comparative genomic hybridization to map these
      deletions and confirmed breakpoints by means of polymerase-chain-reaction assays
      and DNA sequencing. We compared these deletions, along with previously mapped
      deletions, and studied the trans-acting factors binding to these sites in the
      beta-globin locus by using chromatin immunoprecipitation. RESULTS: We found a new
      (deltabeta)(0)-thalassemia deletion and a rare hereditary persistence of fetal
      hemoglobin deletion with identical downstream breakpoints. Comparison of the two
      deletions resulted in the identification of a small intergenic region required
      for gamma-globin (fetal hemoglobin) gene silencing. We mapped a Kurdish beta(0)
      thalassemia deletion, which retains the required intergenic region, deletes other
      surrounding sequences, and maintains fetal hemoglobin silencing. By comparing
      these deletions and other previously mapped deletions, we elucidated a 3.5-kb
      intergenic region near the 5' end of the delta-globin gene that is necessary for
      gamma-globin silencing. We found that a critical fetal hemoglobin silencing
      factor, BCL11A, and its partners bind within this region in the chromatin of
      adult erythroid cells. CONCLUSIONS: By studying three families with unusual
      deletions in the beta-globin locus, we identified an intergenic region near the
      delta-globin gene that is necessary for fetal hemoglobin silencing. (Funded by
      the National Institutes of Health and others.).

PMID- 21879899
TI  - Cord colitis syndrome in cord-blood stem-cell transplantation.
AB  - BACKGROUND: Diarrhea is a frequent complication of hematopoietic stem-cell
      transplantation (HSCT). Important causes of diarrhea after HSCT include acute
      graft-versus-host disease (GVHD), infections, and medications. After the
      transplantation and engraftment of hematopoietic stem cells from umbilical-cord
      blood, we observed a new syndrome of culture-negative, antibiotic-responsive
      diarrhea not attributable to any known cause. METHODS: We conducted a
      retrospective cohort study of all patients undergoing cord-blood HSCT at our
      center between March 2003 and March 2010. The cord colitis syndrome was defined
      as a persistent diarrheal illness in such patients that was not due to acute
      GVHD, viral or bacterial infection, or another identifiable cause. Clinical and
      histopathological features of patients meeting the case definition were further
      analyzed. RESULTS: Among 104 patients who underwent cord-blood HSCT at our
      center, the cord colitis syndrome developed in 11 (10.6%). The 1-year Kaplan
      Meier cumulative probability of meeting the case definition for the syndrome was
      0.16. The median time to onset after transplantation was 131 days (range, 88 to
      314). All patients had a response to a 10-to-14-day course of empirical therapy
      with metronidazole, alone or in combination with a fluoroquinolone. Five of the
      11 patients (45%) had recurrent diarrhea shortly after discontinuation of
      antibiotics, and all patients who had a relapse had a response to reinitiation of
      antibiotic therapy. On histologic examination, all patients with the cord colitis
      syndrome had chronic active colitis, with granulomatous inflammation present in 7
      of 11 patients (64%). CONCLUSIONS: The cord colitis syndrome is clinically and
      histopathologically distinct from acute GVHD and other causes of diarrhea in
      patients who have undergone cord-blood HSCT and is relatively common in this
      patient population. The syndrome should be considered in such patients who have
      diarrhea that is not attributable to other causes.

PMID- 21879900
TI  - Electronic health records and quality of diabetes care.
AB  - BACKGROUND: Available studies have shown few quality-related advantages of
      electronic health records (EHRs) over traditional paper records. We compared
      achievement of and improvement in quality standards for diabetes at practices
      using EHRs with those at practices using paper records. All practices, including
      many safety-net primary care practices, belonged to a regional quality
      collaborative and publicly reported performance. METHODS: We used generalized
      estimating equations to calculate the percentage-point difference between EHR
      based and paper-based practices with respect to achievement of composite
      standards for diabetes care (including four component standards) and outcomes
      (five standards), after adjusting for covariates and accounting for clustering.
      In addition to insurance type (Medicare, commercial, Medicaid, or uninsured),
      patient-level covariates included race or ethnic group (white, black, Hispanic,
      or other), age, sex, estimated household income, and level of education. Analyses
      were conducted separately for the overall sample and for safety-net practices.
      RESULTS: From July 2009 through June 2010, data were reported for 27,207 adults
      with diabetes seen at 46 practices; safety-net practices accounted for 38% of
      patients. After adjustment for covariates, achievement of composite standards for
      diabetes care was 35.1 percentage points higher at EHR sites than at paper-based
      sites (P<0.001), and achievement of composite standards for outcomes was 15.2
      percentage points higher (P=0.005). EHR sites were associated with higher
      achievement on eight of nine component standards. Such sites were also associated
      with greater improvement in care (a difference of 10.2 percentage points in
      annual improvement, P<0.001) and outcomes (a difference of 4.1 percentage points
      in annual improvement, P=0.02). Across all insurance types, EHR sites were
      associated with significantly higher achievement of care and outcome standards
      and greater improvement in diabetes care. Results confined to safety-net
      practices were similar. CONCLUSIONS: These findings support the premise that
      federal policies encouraging the meaningful use of EHRs may improve the quality
      of care across insurance types.

PMID- 21879901
TI  - Clinical practice. Care of the adult patient after sexual assault.

PMID- 21879902
TI  - Images in clinical medicine. Scleroderma.

PMID- 21879903
TI  - Clinical problem-solving. A problem in gestation.

PMID- 21879904
TI  - Cardiac arrest and the limitations of clinical trials.

PMID- 21879905
TI  - Progress in understanding the hemoglobin switch.

PMID- 21879906
TI  - Finding the meaning in meaningful use.

PMID- 21879907
TI  - Blast-related traumatic brain injury in U.S. military personnel.

PMID- 21879897
TI  - A trial of an impedance threshold device in out-of-hospital cardiac arrest.
AB  - BACKGROUND: The impedance threshold device (ITD) is designed to enhance venous
      return and cardiac output during cardiopulmonary resuscitation (CPR) by
      increasing the degree of negative intrathoracic pressure. Previous studies have
      suggested that the use of an ITD during CPR may improve survival rates after
      cardiac arrest. METHODS: We compared the use of an active ITD with that of a sham
      ITD in patients with out-of-hospital cardiac arrest who underwent standard CPR at
      10 sites in the United States and Canada. Patients, investigators, study
      coordinators, and all care providers were unaware of the treatment assignments.
      The primary outcome was survival to hospital discharge with satisfactory function
      (i.e., a score of <=3 on the modified Rankin scale, which ranges from 0 to 6,
      with higher scores indicating greater disability). RESULTS: Of 8718 patients
      included in the analysis, 4345 were randomly assigned to treatment with a sham
      ITD and 4373 to treatment with an active device. A total of 260 patients (6.0%)
      in the sham-ITD group and 254 patients (5.8%) in the active-ITD group met the
      primary outcome (risk difference adjusted for sequential monitoring, -0.1
      percentage points; 95% confidence interval, -1.1 to 0.8; P=0.71). There were also
      no significant differences in the secondary outcomes, including rates of return
      of spontaneous circulation on arrival at the emergency department, survival to
      hospital admission, and survival to hospital discharge. CONCLUSIONS: Use of the
      ITD did not significantly improve survival with satisfactory function among
      patients with out-of-hospital cardiac arrest receiving standard CPR. (Funded by
      the National Heart, Lung, and Blood Institute and others; ROC PRIMED
      ClinicalTrials.gov number, NCT00394706.).

PMID- 21879908
TI  - Blast-related traumatic brain injury in U.S. military personnel.

PMID- 21879909
TI  - Blast-related traumatic brain injury in U.S. military personnel.

PMID- 21879896
TI  - Early versus later rhythm analysis in patients with out-of-hospital cardiac
      arrest.
AB  - BACKGROUND: In a departure from the previous strategy of immediate
      defibrillation, the 2005 resuscitation guidelines from the American Heart
      Association-International Liaison Committee on Resuscitation suggested that
      emergency medical service (EMS) personnel could provide 2 minutes of
      cardiopulmonary resuscitation (CPR) before the first analysis of cardiac rhythm.
      We compared the strategy of a brief period of CPR with early analysis of rhythm
      with the strategy of a longer period of CPR with delayed analysis of rhythm.
      METHODS: We conducted a cluster-randomized trial involving adults with out-of
      hospital cardiac arrest at 10 Resuscitation Outcomes Consortium sites in the
      United States and Canada. Patients in the early-analysis group were assigned to
      receive 30 to 60 seconds of EMS-administered CPR and those in the later-analysis
      group were assigned to receive 180 seconds of CPR, before the initial
      electrocardiographic analysis. The primary outcome was survival to hospital
      discharge with satisfactory functional status (a modified Rankin scale score of
      <=3, on a scale of 0 to 6, with higher scores indicating greater disability).
      RESULTS: We included 9933 patients, of whom 5290 were assigned to early analysis
      of cardiac rhythm and 4643 to later analysis. A total of 273 patients (5.9%) in
      the later-analysis group and 310 patients (5.9%) in the early-analysis group met
      the criteria for the primary outcome, with a cluster-adjusted difference of -0.2
      percentage points (95% confidence interval, -1.1 to 0.7; P=0.59). Analyses of the
      data with adjustment for confounding factors, as well as subgroup analyses, also
      showed no survival benefit for either study group. CONCLUSIONS: Among patients
      who had an out-of-hospital cardiac arrest, we found no difference in the outcomes
      with a brief period, as compared with a longer period, of EMS-administered CPR
      before the first analysis of cardiac rhythm. (Funded by the National Heart, Lung,
      and Blood Institute and others; ROC PRIMED ClinicalTrials.gov number,
      NCT00394706.).

PMID- 21879911
TI  - A novel bunyavirus in China.

PMID- 21879912
TI  - A novel bunyavirus in China.

PMID- 21879913
TI  - A novel bunyavirus in China.

PMID- 21879915
TI  - The Palliative Care Information Act.

PMID- 21879917
TI  - Reforming Medicare--toward a modified Ryan plan.

PMID- 21879918
TI  - Reforming Medicare--toward a modified Ryan plan.

PMID- 21879920
TI  - Anaphylaxis from peanuts ingested by blood donors?

PMID- 21879922
TI  - Kidney paired donation--the next step.

PMID- 21879926
TI  - Strategies for strengthening the evidence base for employee health promotion
      programs.
AB  - Employee health promotion programs have been a visible facet of the American
      workplace for more than 30 years. During that time, a substantial amount of
      research on best practices has been conducted, but because of a lack of
      significant public investment in research funding there is still much to be done.
      Most researchers and practitioners familiar with the literature recognize the
      need to strengthen the evidence base for the field. In this edition of The Art of
      Health Promotion we examine the primary recommendations emerging from a recent
      federally sponsored effort to identify strategies for strengthening the evidence
      base for employee health promotion.

PMID- 21879927
TI  - Intervention Mapping as a framework for developing an intervention at the
      worksite for older construction workers.
AB  - PURPOSE: The purpose of this study was to apply the Intervention Mapping approach
      as a framework in the development of a worksite intervention to improve the work
      ability of construction workers. DESIGN: Development of an intervention by using
      the Intervention Mapping approach. SETTING: Construction worksite. PARTICIPANTS:
      Construction workers aged 45 years and older. MEASURES AND ANALYSIS: According to
      the principles of Intervention Mapping, evidence from the literature was combined
      with data collected from stakeholders (e.g., construction workers, managers,
      providers). RESULTS: The Intervention Mapping approach resulted in an
      intervention with the following components: (1) two individual visits of a
      physical therapist to lower the physical workload, (2) a Rest-Break tool to
      improve the balance between work and recovery, and (3) two empowerment training
      sessions to increase the range of influence at the worksite. CONCLUSIONS:
      Application of Intervention Mapping in the development of a worksite prevention
      program was useful in the construction industry to obtain a positive attitude and
      commitment. Stakeholders could give input regarding the program components as
      well as provide specific leads for the practical intervention strategy. Moreover,
      it also gives insight in the current theoretical and empirical knowledge in the
      field of improving the work ability of older workers in the construction
      industry.

PMID- 21879928
TI  - The SmokingPaST Framework: illustrating the impact of quit attempts, quit
      methods, and new smokers on smoking prevalence, years of life saved, medical
      costs saved, programming costs, cost effectiveness, and return on investment.
AB  - PURPOSE: Describe the specifications of the Smoking Prevalence, Savings, and
      Treatment (SmokingPaST) Framework and show how it can illustrate the impact of
      quit attempts, quit method, number of new smokers, smoking rates of immigrants
      and emigrants, and death rates of smokers and nonsmokers on future smoking
      prevalence rates, program costs, years of life saved, medical costs saved, cost
      effectiveness of programs, and return on investment (ROI). FRAMEWORK
      SPECIFICATIONS: Mathematical relationships among factors in SmokingPaST are
      described. Input variables include baseline smoking rates among current adults,
      new adults, immigrants, and emigrants; population counts for these groups; annual
      quit attempts; and distribution of quit methods. Assumption variables include
      success rate by quit method, death rates of smokers and nonsmokers, annual
      medical costs of smoking, costs per person for four tobacco treatment methods,
      age distribution of quitters, and distribution of medical cost funding by source.
      Output variables include year-end adult smoking rates, successful quitters, years
      of life saved by quitting, medical costs saved by quitting and by not hiring
      smokers, total costs of smoking treatment programs, cost per quitter, cost per
      life-year saved, distribution of medical cost savings from quitting, and ROI of
      treatment costs. APPLICATIONS: The Framework was applied at the employer, county,
      state, and national levels. CONCLUSIONS: The SmokingPaST Framework provides a
      conceptually simple framework that can be applied to any population. It
      illustrates that significant drops in smoking rates can be achieved and
      significant savings in medical costs can be captured by employers as well as
      state and federal governments through tobacco treatment and prevention programs.
      Savings are especially important for reducing state and federal government
      deficits and enhancing job competitiveness.

PMID- 21879929
TI  - Commentaries on "Workplace health promotion will become irrelevant in national
      policy if we do not learn to speak with one voice".

PMID- 21879930
TI  - Speaking with one voice on worksite wellness: the American Cancer Society, the
      American Diabetes Association, and the American Heart Association.

PMID- 21879931
TI  - Finding common ground in the use of financial incentives for employee health
      management: a call for a progress-based approach.

PMID- 21879933
TI  - National prevention strategy released.

PMID- 21879934
TI  - American Journal of Health Promotion presents the recipient of the 2011 Robert F.
      Allen Symbol of H.O.P.E Award.

PMID- 21879935
TI  - Step It UP: a multicomponent intervention to increase stair use in a university
      residence building.
AB  - PURPOSE: Examine the effects of a multicomponent intervention on stair usage.
      DESIGN: Nonrandomized controlled intervention. SETTING: Two multistory university
      dormitories. SUBJECTS: Total of 5711 direct observations of university dormitory
      residents. INTERVENTION: The 2-week "Step It UP" intervention used poster prompts
      and fun/competitive challenges with incentives to encourage residents to take the
      stairs instead of the elevators. MEASURES: Ascending stair and elevator use was
      directly observed and coded for gender at high traffic times in intervention and
      control dormitories for 14 nonconsecutive hours over 1 week each at baseline,
      midintervention, and 1 week postintervention. ANALYSIS: The proportions of
      ascending stair and elevator users were compared using chi(2) analyses. RESULTS:
      Baseline stair use was equal between intervention and control dormitories (24.9%
      and 27.8%, respectively; chi(2)[1, N  =  1849]  =  .08; p  =  .77). Stair use
      significantly increased from baseline in the intervention dormitory to 33.24%
      (chi(2)[1, N  =  2192]  =  18.44; p < .001) compared with no change in the
      control. Stair use returned to baseline in the intervention dormitory at
      postintervention (25.4%; chi(2)[1, N  =  2297]  =  .08; p  =  .78). There were no
      significant differences between genders. CONCLUSION: This multicomponent, short
      duration intervention significantly increased stair usage in a university
      dormitory relative to the control but was unable to sustain the increase when
      prompts were removed. Campaigns to sustain stair use are needed. Formative
      assessment is required to determine what combinations of components may yield the
      most cost-effective approach for future interventions.

PMID- 21879936
TI  - Human papillomavirus and cervical screening: misconceptions undermine adherence.
AB  - PURPOSE: Prophylactic vaccination programs in conjunction with cervical screening
      can significantly reduce the incidence of cervical cancer worldwide. This study
      tested the hypothesis that human papillomavirus (HPV) vaccination can adversely
      affect adherence to cervical screening if the public develops the misconception
      that the HPV vaccination has removed the need for screening. DESIGN: A postal
      survey using a stratified random sample was employed. PARTICIPANTS: Overall, 500
      medical students and 500 nonmedical students of the Aristotle University of
      Thessaloniki were invited to participate. The response rate was 82%. MEASURES: A
      questionnaire was developed assessing demographic characteristics, adherence to
      cervical screening, and awareness and attitudes toward HPV. ANALYSIS: Logistic
      regression was used to assess the impact of HPV awareness and attitudes towards
      HPV vaccination on adherence to Papanicolaou screening, controlling for place of
      origin and mother's screening behavior. RESULTS: Students who believed that
      vaccination against HPV obviated the need for a Papanicolaou test were two times
      less likely to adhere to cervical screening (adjusted odds ratio, 1.89; 95%
      confidence interval, 1.37-2.57; p  =  .0004). The effect was stronger in the
      nonmedical subgroup (adjusted odds ratio, 3.05; 95% confidence interval, 1.85
      5.160; p  =  .0003). CONCLUSION: Findings highlight that misconceptions can
      adversely affect preventive behaviors and reduce the probability of an early
      diagnosis of cervical cancer.

PMID- 21879937
TI  - Expert perspectives on fruit and vegetable consumption in Australia.
AB  - PURPOSE: To examine food system experts' explanations for the consistently low
      level of fruit and vegetable consumption in Australia and what can be done to
      increase it. DESIGN: A qualitative survey of food system experts. SETTING: The
      survey was administered online to experts across Australia between August and
      November 2008 using SurveyMonkey.com. SUBJECTS: Key informants (N  =  332) in
      sectors ranging from farming through food waste disposal; 122 usable responses
      were analyzed. MEASURES: Opinions about fruit and vegetable consumption were
      collected through open-ended questions. Respondent background information was
      also collected. ANALYSIS: Identification of key themes via qualitative analysis.
      RESULTS: Many reasons for inadequate consumption were suggested, most of which
      related to inadequacies in the supply of fruit and vegetables. However, the most
      commonly cited solutions focused on increasing consumer demand. CONCLUSION: The
      incongruence between reasons for inadequate consumption and proposed solutions
      presents a challenge and suggests a need to shift policy priorities towards
      improving the supply of fruit and vegetables. Several well-coordinated approaches
      between the various sectors are needed to maximize outcomes. They include some
      outside the scope of traditional health promotion efforts.

PMID- 21879938
TI  - Increased self-efficacy for vegetable preparation following an online, skill
      based intervention and in-class tasting experience as a part of a general
      education college nutrition course.
AB  - PURPOSE: Assess the effectiveness of the integration of vegetable demonstration
      videos and tasting experiences into a college nutrition course to influence
      students' readiness to change vegetable intake, self-efficacy for vegetable
      preparation, and usual vegetable intake. DESIGN: Quasiexperimental,
      preintervention-postintervention comparisons. SETTING: College nutrition course.
      SUBJECTS: Of the 376 students enrolled in the course, 186 completed the online
      assessments (145 female, 41 male; mean age, 20 years). INTERVENTION: Participants
      viewed online vegetable preparation videos and participated in vegetable tasting
      experiences that featured four target vegetables, one vegetable each month for 4
      months. MEASURES: Preintervention and postintervention online surveys determined
      usual vegetable intake, readiness to change vegetable consumption, and self
      efficacy of vegetable preparation. ANALYSIS: Chi-square distribution and paired
      sample t-tests were used to examine differences preintervention and
      postintervention. RESULTS: Stage of readiness to change vegetable intake shifted
      from contemplation toward preparation (p < .001). Self-efficacy of vegetable
      preparation increased and postintervention self-efficacy was associated with
      total and target vegetable consumption (p  =  .001 and p  =  .005, respectively).
      The average intake of asparagus, one of four target vegetables, increased (p  = 
      .016); similar changes were not observed for target or total vegetable
      consumption. CONCLUSION: Online vegetable demonstration videos may be an
      effective and cost-efficient intervention for increasing self-efficacy of
      vegetable preparation and readiness to increase vegetable consumption among
      college students. More research is needed to determine long-term effects on
      vegetable consumption.

PMID- 21879939
TI  - Stress level, health behaviors, and quality of life in employees joining a
      wellness center.
AB  - PURPOSE: Examine the relationship between stress level and quality of life at a
      worksite wellness center. DESIGN: A survey completed when joining the wellness
      center. Setting . Employee wellness center. SUBJECTS: Survey that inquired about
      stress, health behaviors, and quality of life of more than 13,000 employees
      joining a wellness center. MEASURES: A series of questions about current health
      status and health behaviors. ANALYSIS: Two-sample t-tests assuming unequal
      variances. RESULTS: A total of 2147 of these employees reported having high
      stress levels. Employees with high stress levels had statistically significant
      lower quality of life, more fatigue, and poorer health compared with employees
      with low stress levels. In terms of their ability and motivation to participate
      in wellness programs, the high-stress employees were also less active and had
      less healthy nutritional habits, less support, and less confidence in their
      ability to be active. They also reported having more health problems, including
      high blood pressure, high blood sugar, high cholesterol, and overweight.
      CONCLUSIONS: It appears that employees with high stress levels--those who might
      most benefit from participation in wellness programs--may experience the greatest
      difficulty participating actively in wellness programs because of their lack of
      support, low confidence, and numerous health problems. Perhaps offering tailored
      stress reduction programs for these employees would be beneficial.

PMID- 21879940
TI  - The role of worksite and home smoking bans in smoking cessation among U.S.
      employed adult female smokers.
AB  - PURPOSE: Examine the association of work and home smoking bans with quitting
      behaviors among employed female smokers in the United States. DESIGN: Secondary
      analyses using cross-sectional data from the 2006/2007 Tobacco Use Supplement to
      the Current Population Survey. SUBJECTS: Nationally representative sample of 7610
      U.S. employed female smokers, aged 18 to 64 years, who reported working indoors.
      Setting . N/A. METHODS: Multivariate logistic regression analyses were conducted
      to examine the association of smoking ban policies (complete work and home bans,
      complete work ban only, complete home ban only, and no complete work or home ban)
      with intention to quit in the next 30 days, at least one quit attempt in the past
      year, and sustained abstinence of at least 3 months in the past year. RESULTS:
      Twenty-nine percent of women reported complete work and home smoking bans.
      Smoking bans were not associated with intention to quit and were marginally
      associated with sustained abstinence. Regardless of intention to quit, women with
      complete work and home bans were significantly more likely than those without
      complete work and home bans to report quit attempts. Among women with no
      intention to quit, the odds of having a quit attempt were significantly higher
      among women who had a complete home ban only compared with women without complete
      work and home bans. CONCLUSIONS: Efforts to promote quitting behaviors among
      employed female smokers may be facilitated by increasing rates of complete
      smoking bans at both work and home settings.

PMID- 21879941
TI  - A systematic examination of smoke-free policies in multiunit dwellings in
      Virginia as reported by property managers: implications for prevention.
AB  - PURPOSE: In most states, smoking has been curtailed to some extent in public
      buildings, workplaces, and restaurants. The next frontier for smoke-free policies
      is the multiunit dwelling industry. However, the extent to which smoke-free
      housing currently is available is unknown. The purpose of this study was to
      measure the market for smoke-free housing in Virginia and to identify barriers to
      adopting smoke-free policies. DESIGN: Telephone interviews were conducted with
      property managers of rental apartments, townhouses, senior housing, and public
      housing in four Virginia cities. SETTING: Four cities in Virginia. SUBJECTS: Two
      hundred sixty-three property managers in four cities in Virginia (approximately
      75 property managers per city). MEASURES: Property managers were administered a
      brief telephone survey. RESULTS: Only 33.8% of property managers reported some
      type of smoke-free policy, with only 15% of those policies prohibiting smoking in
      residential units. Most property managers without a smoke-free policy were not
      considering adopting such a policy for a variety of reasons. CONCLUSION: The
      availability of smoke-free multiunit dwellings is severely lacking. This study
      identified a number of science-based and legal misperceptions that may prevent
      the adoption of smoke-free policies. Correction of these misperceptions is
      warranted to increase the availability of smoke-free housing. Such policies will
      be useful in creating environments that support good health practices while
      simultaneously protecting tenants from exposure to secondhand smoke.

PMID- 21879942
TI  - Does the environment moderate the impact of a mass media campaign to promote
      walking?
AB  - PURPOSE: To examine if a mass media campaign influenced walking differently in
      people in different physical environments. DESIGN: Quasi-experimental study.
      Setting . Wheeling, West Virginia. PARTICIPANTS: Random sample of adults age 50
      to 65 years, response rate: 72.1% (n  =  719 in intervention community, n  =  753
      in comparison community). INTERVENTION: Mass media campaign. MEASURES: Self
      reported measures were used in before and after telephone surveys for walking and
      the physical environment. Measures included 11 environmental walkability items,
      from which two subscales (i.e., usable sidewalks/aesthetics and facilities) were
      extracted. ANALYSIS: Multiple linear regression. RESULTS: Overall, walking
      increased by 2.7 minutes per week (standard deviation [SD]  =  231.1, not
      significant [NS]). When confined to those insufficiently active at baseline
      (i.e., <30 minutes per day) the minutes walked increased by 92.1 minutes (SD  = 
      152.9, p < .001). For the insufficiently active at baseline in the top half of
      the environmental factor of usable sidewalks, walking increased by 19 minutes
      more than in the bottom half (NS). For the factor of aesthetics and facilities,
      people in the more walkable environment increased walking by 87 minutes more than
      those in the bottom half (p < .001). CONCLUSION: In this community-wide physical
      activity, intervention changes in walking after the campaign were significantly
      moderated by some environmental attributes. This contributes to the limited
      evidence on the impact of the environment in enhancing community physical
      activity interventions. This finding needs to be replicated in other community
      interventions with greater environmental variation.

PMID- 21879943
TI  - The effects of commuter pedestrian traffic on the use of stairs in an urban
      setting.
AB  - PURPOSE: Most public health physical activity guidelines now encourage people to
      look for opportunities to accumulate physical activity throughout the day.
      Climbing stairs in lieu of riding escalators is a prime opportunity to make
      healthier choices that promote active living. The purpose of this investigation
      was to examine the effects of pedestrian commuter traffic on choices to ride an
      escalator, walk up an escalator, or walk up adjacent stairs in a busy urban
      subway station at rush hour. DESIGN: A total of 9766 commuters were observed by
      two recorders for a 2.5-hour period during the morning rush hour over 8 weeks as
      to whether the commuters walked up stairs or rode an adjacent escalator in a
      subway station. The number of observations per 5-minute block was recorded, and
      an index of commuter traffic was computed. Demographic information and use of
      escalators/stairs were also recorded. SETTING: An urban subway station with a two
      flight staircase adjacent to an escalator. PARTICIPANTS: Adult commuters
      travelling to work during the morning rush hour. MEASURES: Physical activity
      choices were examined in relation to commuter traffic. Demographic information,
      such as age, race, and weight status, were also considered. ANALYSIS: A chi(2)
      analysis was used to examine differences in proportions across variables of
      interest. Means were compared by using multivariate analysis of variance, and
      confidence intervals were computed. RESULTS: During the least-heavy commuter
      traffic period, only 11.2% of commuters chose to walk up the stairs, whereas
      significantly more did so during moderate 18.7% and high 20.8% commuter traffic
      periods (chi(2)  =  61.8, p < .001). During low-traffic times, significantly more
      commuters (21.4%) walked up the escalators compared with moderate-traffic (18.0%)
      or high-traffic (18.3%) periods. African-American commuters passively rode the
      escalator more (68.2%) than white commuters (56.7%), and their patterns were less
      affected by commuter traffic (p < .05). CONCLUSION: Congestion in public places
      can have a significant effect on opportunities for choosing active versus passive
      options in moving through public places. Urban planners should consider this when
      designing facilities in busy locations.

PMID- 21879944
TI  - Associations between natural amenities, physical activity, and body mass index in
      100 North Carolina counties.
AB  - PURPOSE: To examine associations between county-level natural amenities, physical
      activity (PA), and body mass index (BMI). DESIGN AND SETTING: Cross-sectional
      study among 100 North Carolina counties. MEASURES: We obtained percentage of
      county residents meeting PA criteria and county-wide means for reported height
      and weight from the North Carolina Behavioral Risk Factor Surveillance System,
      combining years 2003, 2005, and 2007. The county natural amenities scale was the
      independent variable. Potential county-level covariates were percentage rural,
      percentage black, median age, and median household income (Census 2000).
      ANALYSIS: We conducted weighted bivariate and linear regression analyses to
      examine relationships between natural amenities, aggregate PA, and aggregate BMI.
      RESULTS: BMI and natural amenities were negatively associated (parameter estimate
      =  -.13 (.06), p  =  .03). When percentage meeting PA criteria was included, the
      parameter estimate attenuated 15%. CONCLUSION: There was an inverse relationship
      between natural amenities and BMI, partially mediated by PA.

PMID- 21879945
TI  - Changes in physician costs among high-cost transcendental meditation
      practitioners compared with high-cost nonpractitioners over 5 years.
AB  - PURPOSE: To determine whether the Transcendental Meditation (TM) technique can
      affect the physician costs of consistently high-cost people. DESIGN: Quasi
      experimental, longitudinal, cost-minimization evaluation. This 14-year,
      preintervention-postintervention study retrospectively assessed government
      payments to physicians for treating the TM and no-treatment (NT) groups. SETTING:
      Province of Quebec, Canada. PARTICIPANTS: The highest-spending 10% of 1418 Quebec
      health insurance enrollees who practiced the TM technique were compared with the
      highest 10% of 1418 subjects who were randomly selected from enrollees of the
      same age, sex, and region. TM participants had chosen to begin the technique
      prior to choosing to enter the study. MEASURES: Annual payments to private
      physicians in all treatment settings. The Quebec government health insurance
      agency provided the total physician payments for each of the 2836 subjects from
      1981 to 1994. Other medical expense data for individuals were unavailable. Data
      were adjusted for medical cost inflation. ANALYSIS: For each subject, least
      squares regression slopes were calculated to estimate preintervention and
      postintervention annual rates of change in payments. The groups' means, slopes,
      and medians were compared using both parametric and nonparametric tests. RESULTS:
      Before starting meditation, the yearly rate of increase in payments to physicians
      between groups was not significantly different. After commencing meditation, the
      TM group's mean payments declined $44.93 annually (p  =  .004), whereas the NT
      comparison group's payments exhibited nonsignificant changes. After 1 year, the
      TM group decreased 11%, and after 5 years their cumulative reduction was 28% (p 
      =  .001). CONCLUSIONS: The results suggest the intervention may be an effective
      method for reducing physician costs. Randomized studies are recommended.

PMID- 21879948
TI  - Role of size and composition of traffic and agricultural aerosols in the
      molecular responses triggered in airway epithelial cells.
AB  - The increased levels of fine particles in the atmosphere are suspected of
      aggravating cardiopulmonary diseases, but the determinants of particle toxicity
      are poorly understood. This work aims at studying the role of composition and
      size in the toxicity of size-segregated particulate matter (PM) collected at
      different sites on human bronchial epithelial cells. PM were sampled at a traffic
      urban site (Urb S) and a rural site (Rur S) during the pesticide-spreading
      period. Ultrafine (UF), fine (F), and coarse (C) PM were characterized by their
      shape and chemical composition. Whatever the site, the finest PM (UF and F)
      induced the mRNA expression of CYP1A1, a biomarker of polyaromatic hydrocarbons
      (PAH) exposure, NQO-1 and heme HO-1, two antioxidant responsive element-driven
      genes; and two effect biomarkers, GM-CSF, a proinflammatory cytokine and
      amphiregulin (AR), a growth factor. C PM have a low or no effect. Interestingly,
      AR is more strongly induced by rural PM at the same mass exposure. These
      discrepancies suggest involvement of PM chemical composition: rural PM bearing
      the characteristics of aged aerosols with a high content of water-soluble
      components, and PM at urban kerbside sites containing mainly water-insoluble
      components. To conclude, we provide evidence that the finest PM fractions,
      whatever their origin, are more prone to induce exposure and effect biomarkers.
      The AR differential expression suggests a source-dependent effect requiring
      further investigation because of the role of this growth factor in airway
      remodeling, a characteristic feature of chronic lung respiratory diseases
      exacerbated by particulate pollution.

PMID- 21879949
TI  - Exposure to fluoropolymers and VOCs during spray sealant product use.
AB  - Fluoropolymer based tile and fabric spray sealants were evaluated for the release
      of airborne fluoropolymer constituents and volatile organic compounds (VOCs)
      during typical product use scenarios in a simulated bathroom and a simulated
      recreational vehicle. Fluoride was quantified after oxygen bomb digestion of
      airborne spray collected from personal, area, and surface samples. VOCs were
      quantified by gas chromatography/mass spectrometry (GC/MS) and gas
      chromatography/flame ionization spectrometry (GC/FID). Tile grout sealant
      contained approximately 1% acrylic fluoropolymer resin and 90% VOCs not including
      propellants. VOCs were short- and medium- chain methylated isoparaffinic
      hydrocarbons. When horizontally spraying a bathroom shower floor, grout spray
      sealant released a non-detectable amount of fluoride (<0.8 ug/m3) and 400-1400
      mg/m3 total VOCs. When vertically spraying a shower wall, up to 2.0 ug/m3 of
      fluoride and from 1000 to 2300 mg/m3 total VOCs were detected. Fabric spray
      sealant contained 1% acrylic fluoropolymer resin and approximately 90% VOCs
      including perchloroethylene (PERC). Fabric spray released from 0.5 to 2.3 ug/m3
      fluoride inside a recreational vehicle in the absence of crosswinds and less than
      0.5 ug/m3 fluoride in the presence of a 10 mph crosswind. VOC release measured
      240-938 mg/m3 without crosswinds and 161-522 mg/m3 with crosswinds. These studies
      show that fluoropolymer constituents from fluorinated spray sealants were near
      non-detectable levels in the breathing zone in nearly all samples while VOCs were
      measured at elevated levels (>400 mg/m3). The toxicological consequences of
      elevated VOCs during sealant spraying and the effects of certain fluoropolymer
      constituents are discussed.

PMID- 21879950
TI  - Quantitative exposure matrix for asphalt fume, total particulate matter, and
      respirable crystalline silica among roofing and asphalt manufacturing workers.
AB  - This paper summarizes available data on worker exposures to asphalt fume (soluble
      fraction), total particulate matter, and respirable crystalline silica (quartz)
      [hereinafter RCS] over a 30-year period in Owens Corning's asphalt production and
      roofing manufacturing plants. For the period 1977 through 2006, the air
      monitoring database contains more than 1,400 personal samples for asphalt fume
      (soluble fraction), 2,400 personal samples for total particulate, and 1,300
      personal samples for RCS. Unique process-job categories were identified for the
      asphalt production and roofing shingle manufacturing plants. Quantitative
      exposures were tabulated by agent, process-job, and calendar period to form an
      exposure matrix for use in subsequent epidemiologic studies of the respiratory
      health of these workers. Analysis of time trends in exposure data shows
      substantial and statistically significant exposure reductions for asphalt fume
      (soluble fraction), total particulate matter, and respirable crystalline silica
      at Owens Corning plants. Cumulative distribution plots for the most recent
      sampling period (2001-2006) show that 95% of the asphalt fume (soluble fraction)
      measurements were less than 0.25 mg/m3; 95% of the total particulate measurements
      were less than 2.2 mg/m3; and 95% of the RCS measurements were less than 0.05
      mg/m3. Several recommendations are offered to improve the design of future
      monitoring efforts.

PMID- 21879952
TI  - Partnership to promote preventive care for pets.

PMID- 21879953
TI  - More on proposed changes to veterinary curriculum.

PMID- 21879954
TI  - What is your diagnosis? Spinal fracture.

PMID- 21879955
TI  - What is your diagnosis? Calcinosis circumscripta.

PMID- 21879956
TI  - What is your neurologic diagnosis? Blastomyces dermatitidis encephalitis.

PMID- 21879957
TI  - Pathology in practice. Bacterial pseudomycetoma.

PMID- 21879958
TI  - Relationships between more than two variables.

PMID- 21879959
TI  - Effects of nutrition choices and lifestyle changes on the well-being of cats, a
      carnivore that has moved indoors.

PMID- 21879960
TI  - Compendium of animal rabies prevention and control, 2011.

PMID- 21879961
TI  - Survey of colleges and schools of veterinary medicine regarding education in
      complementary and alternative veterinary medicine.
AB  - OBJECTIVE: To obtain information on educational programs offered in complementary
      and alternative veterinary medicine (CAVM) among AVMA Council on Education (COE)
      accredited colleges and schools of veterinary medicine. DESIGN: Survey. SAMPLE:
      41 COE-accredited colleges and schools of veterinary medicine. PROCEDURE: A
      questionnaire was e-mailed to academic deans at all COE-accredited colleges and
      schools of veterinary medicine. RESULTS: Responses were received from 34 of 41
      schools: 26 in the United States, 2 in Canada, 3 in Australia and New Zealand,
      and 3 in Europe. Sixteen schools indicated that they offered a CAVM course.
      Nutritional therapy, acupuncture, and rehabilitation or physical therapy were
      topics most commonly included in the curriculum. One school required a course in
      CAVM; all other courses were elective, most of which were 1 to 2 credit hours.
      Courses were usually a combination of lecture and laboratory; 2 were lecture
      only, and 1 was laboratory only. Of the 18 schools that reported no courses in
      CAVM, many addressed some CAVM topics in other courses and 4 indicated plans to
      offer some type of CAVM course within the next 5 years. CONCLUSIONS AND CLINICAL
      RELEVANCE: The consensus among survey respondents was that CAVM is an important
      topic that should be addressed in veterinary medical education, but opinions
      varied as to the appropriate framework. The most common comment reflected strong
      opinions that inclusion of CAVM in veterinary medical curricula must be evidence
      based. Respondents indicated that students should be aware of CAVM modalities
      because of strong public interest in CAVM and because practitioners should be
      able to address client questions from a position of knowledge.

PMID- 21879962
TI  - Development of new canine and feline preventive healthcare guidelines designed to
      improve pet health.

PMID- 21879963
TI  - Effects of intravenous administration of lactated Ringer's solution on
      hematologic, serum biochemical, rheological, hemodynamic, and renal measurements
      in healthy isoflurane-anesthetized dogs.
AB  - OBJECTIVE: To determine the hematologic, serum biochemical, rheological,
      hemodynamic, and renal effects of IV administration of lactated Ringer's solution
      (LRS) to healthy anesthetized dogs. DESIGN: 4-period, 4-treatment cross-over
      study. ANIMALS: 8 healthy mixed-breed dogs. PROCEDURES: Each dog was
      anesthetized, mechanically ventilated, instrumented, and randomly assigned to
      receive LRS (0, 10, 20, or 30 mL/kg/h [0, 4.5, 9.1, or 13.6 mL/lb/h]), IV, on 4
      occasions separated by at least 7 days. Blood hemoglobin concentration and serum
      total protein, albumin, lactate, and electrolyte concentrations; PCV; colloid
      osmotic pressure; arterial and venous pH and blood gases (Po2; Pco2); whole blood
      and plasma viscosity; arterial and venous blood pressures; cardiac output;
      results of urinalysis; urine production; glomerular filtration rate; and
      anesthetic recovery times were monitored. Oxygen delivery, vascular resistance,
      stroke volume, pulse pressure, and blood and plasma volume were calculated.
      RESULTS: Increasing rates of LRS administration resulted in dose-dependent
      decreases in PCV; blood hemoglobin concentration and serum total protein and
      albumin concentrations; colloid osmotic pressure; and whole blood viscosity.
      Plasma viscosity; serum electrolyte concentrations; data from arterial and venous
      blood gas analysis; glomerular filtration rate; urine production; heart rate;
      pulse, central venous, and arterial blood pressures; pulmonary vascular
      resistance; and oxygen delivery did not change. Pulmonary artery pressure, stroke
      volume, and cardiac output increased, and systemic vascular resistance decreased.
      CONCLUSIONS AND CLINICAL RELEVANCE: Conventional IV infusion rates of LRS to
      isoflurane-anesthetized dogs decreased colligative blood components; increased
      plasma volume, pulmonary artery pressure, and cardiac output; and did not change
      urine production or oxygen delivery to tissues.

PMID- 21879964
TI  - Association between hepatic histopathologic lesions and clinical findings in dogs
      undergoing surgical attenuation of a congenital portosystemic shunt: 38 cases
      (2000-2004).
AB  - OBJECTIVE: To review hepatic histopathologic lesions in dogs undergoing surgical
      attenuation of a congenital portosystemic shunt (CPSS) in relation to clinical
      findings and tolerance of complete surgical attenuation. DESIGN: Retrospective
      case series. ANIMALS: 38 dogs that underwent surgical attenuation of a CPSS.
      PROCEDURES: Hepatic histologic examination findings and medical records of dogs
      undergoing surgical attenuation of a single CPSS between August 2000 and July
      2004 were reviewed. Liver biopsy specimens were obtained from 38 dogs during
      surgery prior to complete (n = 16) or partial (22) attenuation of a CPSS and from
      13 of the same dogs a median of 3 months following surgical attenuation. RESULTS:
      Portal tracts were inadequate for interpretation in 2 liver biopsy specimens.
      Liver biopsy specimens obtained prior to surgical attenuation of a CPSS had a
      lack of identifiable portal veins (13/36 dogs), hepatic arteriolar proliferation
      (25/36), ductular reaction (5/36), steatosis (16/38), and iron accumulation
      (32/38). Lack of identifiable portal veins on histologic examination was
      associated with increased hepatic arteriolar proliferation, decreased tolerance
      to complete surgical CPSS attenuation, and decreased opacification of
      intrahepatic portal vessels on portovenography. Ductular reaction was always
      associated with failure to tolerate complete surgical attenuation of a CPSS.
      Surgical CPSS attenuation resulted in significant clinical, serum biochemical,
      and portovenographic changes indicative of improved liver function, but only
      subtle changes in hepatic histologic examination findings. CONCLUSIONS AND
      CLINICAL RELEVANCE: Dogs without identifiable intrahepatic portal veins that had
      a ductular reaction on hepatic histologic examination were less likely to
      tolerate complete attenuation of a CPSS.

PMID- 21879965
TI  - Potential zinc phosphide rodenticide toxicosis in dogs: 362 cases (2004-2009).
AB  - OBJECTIVE: To evaluate records of dogs exposed to zinc phosphide rodenticides and
      characterize the patient population, including breed, sex, age, body weight, time
      since exposure, development of clinical signs, clinical signs observed,
      treatments performed, veterinary care received, outcome, and overall prognosis.
      DESIGN: Retrospective case series. ANIMALS: 362 dogs with presumed zinc phosphide
      exposure. PROCEDURES: An electronic computer database from an animal poison
      control center was searched to identify dogs that ingested zinc phosphide between
      November 2004 and July 2009. RESULTS: Accurate information regarding development
      of clinical signs was available in 94.5% (342/362) of cases. Over half the dogs
      (58.8% [201/342]) did not develop clinical signs, and specific clinical signs
      were reported for the remaining 41.2% (141/342) of dogs. There were 180 total
      clinical signs recorded for these 141 dogs, with some dogs having developed > 1
      category of clinical signs. Clinical signs involving the gastrointestinal tract
      were the most commonly reported type of clinical sign (66.7% [n = 120/180
      reported signs]), followed by generalized malaise (17.8% [32/180]), CNS signs
      (8.9% [16/180]), respiratory signs (3.3% [6/180]), and cardiovascular signs (1.7%
      [3/180]). Approximately 65% (234/362) of patients received veterinary care
      (including decontamination via induction of emesis, gastric lavage, or activated
      charcoal administration), and of these dogs, 51.3% (120/234) were hospitalized.
      For the 296 dogs for which survival data were available, the survival rate was
      98.3% (291/296). CONCLUSIONS AND CLINICAL RELEVANCE: Overall, the prognosis for
      zinc phosphide toxicosis was good. Zinc phosphide rodenticide toxicosis is a
      potential public health concern, and veterinary staff should be aware of this
      commonly used rodenticide.

PMID- 21879966
TI  - Recurrent vestibular paroxysms associated with systemic hypertension in a dog.
AB  - CASE DESCRIPTION: A 9-year-old 19.7-kg (43.3-lb) spayed female Australian
      Shepherd was examined for an increase in frequency of episodic neurologic signs,
      often occurring upon exercise. CLINICAL FINDINGS: Between episodes of neurologic
      signs, the dog was considered clinically normal on the basis of findings on
      physical and neurologic examinations. An episode of ataxia with central
      vestibular signs was induced by exercising the patient in the hospital. All
      clinicopathologic values were within reference ranges, as were findings on
      magnetic resonance imaging of the brain and peripheral vestibular system.
      Systolic blood pressures of 180 to 200 mm Hg were recorded, and systemic
      hypertension was diagnosed. TREATMENT AND OUTCOME: While the dog received
      amlodipine and enalapril, blood pressure returned to within reference range, and
      episodes of neurologic signs no longer occurred. When clinical signs later
      recurred, systolic blood pressure was again found to be high. Following an
      increase in medication dosage, blood pressure normalized, and only 4 further
      episodes of neurologic signs were observed during a follow-up period totaling 30
      months. CLINICAL RELEVANCE: Transient ischemic attack is a common diagnosis in
      humans but has not been described for dogs. In humans, it is defined as focal
      brain dysfunction caused by vascular disease that resolves completely in less
      than 24 hours and is often recurrent. Systemic hypertension is one of the most
      common preexisting conditions. We propose that the dog in the present report had
      clinical signs and diagnostic test results supportive of a diagnosis of transient
      ischemic attack.

PMID- 21879967
TI  - Extralabel use of cabergoline in the treatment of a pituitary adenoma in a rat.
AB  - CASE DESCRIPTION: A 0.65-kg (1.43-lb) 24-month-old sexually intact male albino
      pet rat was examined because of a 3-week history of hypodipsia, apparent
      blindness, and sudden change in behavior. CLINICAL FINDINGS: The rat was able to
      move around its cage but appeared unaware of its surroundings, was visually
      unresponsive, and seemed unusually aggressive. The rat's hind limbs appeared
      mildly paretic, and it had sporadic difficulty placing its hind limbs on a flat
      surface. Given the rat's age, history, and physical examination findings, the
      primary differential diagnosis was a pituitary tumor. Magnetic resonance imaging
      (MRI) of the rat's brain was performed and revealed a large pituitary mass, which
      was indicative of a tumor. TREATMENT AND OUTCOME: Cabergoline (0.6 mg/kg [0.27
      mg/lb], PO, q 72 h) was administered. On follow-up MRI 2 months later, the
      pituitary mass had substantially decreased in size. For 6 months following the
      second MRI study, the rat continued to receive the same dosage of cabergoline and
      had no clinical signs of disease or unusual behavior. However, at 8.5 months
      after the start of the treatment, the rat was in poor condition and had clinical
      signs similar to those initially. A third MRI study was performed and revealed
      substantial regrowth of the mass. The rat was euthanized and a necropsy was
      performed; a histopathologic diagnosis of pituitary adenoma was made. CLINICAL
      RELEVANCE: Pituitary adenomas have long been recognized as a common finding in
      geriatric rats (> 18 months old). Affected rats may respond favorably to oral
      administration of cabergoline.

PMID- 21879968
TI  - Clinical implications of high liver enzyme activities in hospitalized neonatal
      foals.
AB  - OBJECTIVE: To determine whether high liver enzyme activities were negatively
      associated with outcome in sick neonatal foals as compared with foals that did
      not have high liver enzyme activities. DESIGN: Retrospective case-control study.
      ANIMALS: 147 foals < 30 days old with high gamma-glutamyltransferase activity,
      high sorbitol dehydrogenase activity, or both (case foals) and 263 foals < 30
      days old with gamma-glutamyltransferase and sorbitol dehydrogenase activities
      within reference limits (control foals). PROCEDURES: Medical records were
      reviewed for information on signalment, physical examination findings, and
      results of hematologic and serum biochemical analyses performed at the time of
      admission to a veterinary medical teaching hospital. RESULTS: Case foals were
      significantly more likely to die or be euthanized, compared with control foals
      (odds ratio, 2.22; 95% confidence interval, 1.28 to 3.85). Case foals were
      significantly more likely than control foals to have sepsis, and septic foals
      were significantly less likely to survive than were nonseptic foals. For case
      foals, other factors associated with a greater likelihood of nonsurvival were
      higher anion gap and higher logarithm of aspartate aminotransferase activity.
      When sepsis status was controlled for, the presence of high liver enzyme
      activities was not significantly associated with outcome. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that high liver enzyme activities were
      common in sick neonatal foals, especially foals with sepsis. Foals with high
      liver enzyme activities were more likely to be septic, and septic foals were less
      likely to survive than were foals without sepsis. However, high liver enzyme
      activities alone were not a useful negative prognostic indicator.

PMID- 21879969
TI  - Effects of early pregnancy diagnosis by palpation per rectum on pregnancy loss in
      dairy cattle.
AB  - OBJECTIVE: To determine the effect of palpation per rectum (PPR) by use of 1 or 2
      fetal membrane slips (FMSs) for pregnancy diagnosis during early gestation on
      pregnancy loss in dairy cattle. DESIGN: Controlled, randomized block design.
      ANIMALS: 928 healthy pregnant cattle. PROCEDURES: All cattle were determined to
      be pregnant by use of transrectal ultrasonography at approximately day 31 after
      estrus and randomly allocated into 2 groups (control group [n = 476 cows] and
      palpation group [452]). The control group was not subjected to pregnancy
      diagnosis via PPR. The palpation group was subdivided into 2 groups (PPR FMS 1 [n
      = 230 cows] and PPR FMS 2 [222]), which involved PPR and pregnancy diagnosis via
      1 or 2 FMSs, respectively, during the same examination, which was performed by 1
      veterinarian between days 34 and 43 after estrus. All cattle were reevaluated by
      use of transrectal ultrasonography on days 45 and 60 to determine viability of
      the embryo and fetus, respectively. RESULTS: Overall pregnancy loss between days
      31 and 60 was 14.1%. Pregnancy loss for the control, PPR FMS 1, and PPR FMS 2
      groups from days 31 to 60 was 14.5%, 12.6%, and 14.9%, respectively. Embryonic
      pregnancy loss for the control, PPR FMS 1, and PPR FMS 2 groups was 12.4%, 9.1%,
      and 9.5%, respectively. Fetal pregnancy loss for the same groups was 2.4%, 3.8%,
      and 5.9%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Pregnancy diagnosis
      via 1 or 2 FMSs performed during PPR in early gestation did not increase
      pregnancy loss in dairy cattle.

PMID- 21879971
TI  - Accuracy of the use of triaxial accelerometry for measuring daily activity as a
      predictor of daily maintenance energy requirement in healthy adult Labrador
      Retrievers.
AB  - OBJECTIVE: To determine accuracy of the use of triaxial accelerometry for
      measuring daily activity as a predictor of maintenance energy requirement (MER)
      in healthy adult Labrador Retrievers. ANIMALS: 10 healthy adult Labrador
      Retrievers. PROCEDURES: Dogs wore an accelerometer for two 2-week periods, with
      data on daily activity successfully collected for 24 to 26 days. These data,
      along with body weight, were used as independent variables in a multiple linear
      regression model to predict the dependent variable of daily MER. The predictive
      accuracy of the model was compared with that of a model that excluded activity.
      Dietary energy intake at a stated amount of body weight stability was used as an
      equivalent measure of MER in these analyses. RESULTS: The multiple linear
      regression model that included body weight and daily activity as independent
      variables could be used to predict observed MER with a mean absolute error of
      63.5 kcal and an SE of estimation of 94.3 kcal. Removing activity from the model
      reduced the predictive accuracy to a mean absolute error of 129.8 kcal and an SE
      of estimation of 165.4 kcal. CONCLUSIONS AND CLINICAL RELEVANCE: Use of triaxial
      accelerometers to provide an independent variable of daily activity yielded a
      marked improvement in predictive accuracy of the regression model, compared with
      that for a model that used only body weight. Improved accuracy in estimations of
      MER could be made for each dog if an accelerometer was used to record its daily
      activity.

PMID- 21879972
TI  - Assessment of repeatability of a wireless, inertial sensor-based lameness
      evaluation system for horses.
AB  - OBJECTIVE: To determine repeatability of a wireless, inertial sensor-based
      lameness evaluation system in horses. ANIMALS: 236 horses. PROCEDURES: Horses
      were from 2 to 29 years of age and of various breeds and lameness disposition.
      All horses were instrumented with a wireless, inertial sensor-based motion
      analysis system on the head (accelerometer), pelvis (midline croup region
      [accelerometer]), and right forelimb (gyroscope) before evaluation in 2
      consecutive trials, approximately 5 minutes apart, as the horse was trotted in a
      straight line. Signal-processing algorithms generated overall trial asymmetry
      measures for vertical head and pelvic movement and stride-by-stride differences
      in head and pelvic maximum and minimum positions between right and left sides of
      each stride. Repeatability was determined, and trial difference was determined
      for groups of horses with various numbers of strides for which data were
      collected per trial. RESULTS: Inertial sensor-based measures of torso movement
      asymmetry were repeatable. Repeatability for measures of torso asymmetry for
      determination of hind limb lameness was slightly greater than that for forelimb
      lameness. Collecting large numbers of strides degraded stride-to-stride
      repeatability but did not degrade intertrial repeatability. CONCLUSIONS AND
      CLINICAL RELEVANCE: The inertial sensor system used to measure asymmetry of head
      and pelvic movement as an aid in the detection and evaluation of lameness in
      horses trotting in a straight line was sufficiently repeatable to investigate for
      clinical use.

PMID- 21879973
TI  - Comparison of the effects of racemic ketamine and S-ketamine for anesthesia in
      Rheem gazelles (Gazella subgutturosa marica) and Subgutturosa gazelles (Gazella
      subgutturosa subgutturosa).
AB  - OBJECTIVE: To evaluate effects of racemic ketamine and S-ketamine in gazelles.
      ANIMALS: 21 male gazelles (10 Rheem gazelles [Gazella subgutturosa marica] and 11
      Subgutturosa gazelles [Gazella subgutturosa subgutturosa]), 6 to 67 months old
      and weighing (mean+/-SD) 19 +/- 3 kg. PROCEDURES: In a randomized, blinded
      crossover study, a combination of medetomidine (80 MUg/kg) with racemic ketamine
      (5 mg/kg) or S-ketamine (3 mg/kg) was administered i.m.. Heart rate, blood
      pressure, respiratory rate, rectal temperature, and oxygen saturation (determined
      by means of pulse oximetry) were measured. An evaluator timed and scored
      induction of, maintenance of, and recovery from anesthesia. Medetomidine was
      reversed with atipamezole. The alternate combination was used after a 4-day
      interval. Comparisons between groups were performed with Wilcoxon signed rank and
      paired t tests. RESULTS: Anesthesia induction was poor in 2 gazelles receiving S
      ketamine, but other phases of anesthesia were uneventful. A dominant male
      required an additional dose of S-ketamine (0.75 mg/kg, i.m.). After
      administration of atipamezole, gazelles were uncoordinated for a significantly
      shorter period with S-ketamine than with racemic ketamine. Recovery quality was
      poor in 3 gazelles with racemic ketamine. No significant differences between
      treatments were found for any other variables. Time from drug administration to
      antagonism was similar between racemic ketamine (44.5 to 53.0 minutes) and S
      ketamine (44.0 to 50.0 minutes). CONCLUSIONS AND CLINICAL RELEVANCE:
      Administration of S-ketamine at a dose 60% that of racemic ketamine resulted in
      poorer induction of anesthesia, an analogous degree of sedation, and better
      recovery from anesthesia in gazelles with unremarkable alterations in physiologic
      variables, compared with racemic ketamine.

PMID- 21879974
TI  - Comparison of temporospatial and kinetic variables of walking in small and large
      dogs on a pressure-sensing walkway.
AB  - OBJECTIVE: To compare temporospatial variables (TSVs) and kinetic variables (KVs)
      for fore-limbs and hind limbs of small and large dogs of various breeds during
      walking and to determine associations among body weight (BW), TSVs, and KVs in
      these groups. ANIMALS: 12 adult dogs with no evidence of lameness. PROCEDURES:
      Dogs (grouped according to BW as small [< 10 kg; n = 6] or large [> 25 kg; 6])
      were walked in a straight line at their preferred velocity on a wooden platform
      with an embedded pressure-sensing walkway. Five valid trials were analyzed for
      each dog; mean TSVs and KVs were determined for each group. The TSVs and KVs for
      forelimbs and hind limbs were compared between groups, and correlations among BW,
      TSVs, and KVs were determined. RESULTS: Small dogs had significantly smaller TSVs
      and KVs than did large dogs. Temporal variables of small dogs and absolute
      vertical force variables of small and large dogs increased as BW increased.
      However, normalized peak vertical force and weight distribution values among the
      4 limbs were similar between groups. CONCLUSIONS AND CLINICAL RELEVANCE:
      Substantial similarities and differences were detected in gait characteristics
      between small and large dogs. Results indicated TSVs and KVs can be used for
      comparison of the walking gait between dogs or for comparison of variables
      between limbs in an individual dog. Use of the pressure-sensing walkway is a
      simple method for acquisition of TSVs and KVs for large and small dogs.

PMID- 21879975
TI  - Evaluation of the effect of computed tomography scan protocols and freeform
      fabrication methods on bone biomodel accuracy.
AB  - OBJECTIVE: To assess the effect of computed tomography (CT) scan protocols
      (radiation amounts) and fabrication methods on biomodel accuracy and variability.
      SAMPLE: Cadaveric femur of a Basset Hound. PROCEDURES: Retroreconstructions (n =
      158) were performed of 16 original scans and were visually inspected to select 17
      scans to be used for biomodel fabrication. Biomodels of the 17 scans were made in
      triplicate by use of 3 freeform fabrication processes (stereolithography, fused
      deposition modeling, and 3-D printing) for 153 models. The biomodels and original
      bone were measured by use of a coordinate measurement machine. RESULTS:
      Differences among fabrication methods accounted for 2% to 29% of the total
      observed variation in inaccuracy and differences among method-specific radiation
      configurations accounted for 4% to 44%. Biomodels underestimated bone length and
      width and femoral head diameter and overestimated cortical thickness. There was
      no evidence of a linear association between thresholding adjustments and biomodel
      accuracy. Higher measured radiation dose led to a decrease in absolute relative
      error for biomodel diameter and for 4 of 8 cortical thickness measurements.
      CONCLUSIONS AND CLINICAL RELEVANCE: The outside dimensions of biomodels have a
      clinically acceptable accuracy. The cortical thickness of biomodels may
      overestimate cortical thickness. Variability among biomodels was caused by model
      fabrication reproducibility and, to a lesser extent, by the radiation settings of
      the CT scan and differences among fabrication methods.

PMID- 21879976
TI  - Anatomic, histologic, and two-dimensional-echocardiographic evaluation of mitral
      valve anatomy in dogs.
AB  - OBJECTIVE: To compare echocardiographic variables of dogs with postmortem
      anatomic measurements and histologic characteristics of the mitral valve (MV).
      ANIMALS: 21 cardiologically normal dogs. PROCEDURES: The MV was measured
      echocardiographically by use of the right parasternal 5-chamber long-axis view.
      Dogs were euthanized, and anatomic measurements of the MV annulus (MVa) were
      performed at the level of the left circumflex coronary artery. Mitral valve
      leaflets (MVLs) and chordae tendineae were measured. Structure of the MVLs was
      histologically evaluated in 3 segments (proximal, middle, and distal). RESULTS:
      Echocardiographic measurements of MVL length did not differ significantly from
      anatomic measurements. A positive correlation was detected between body weight
      and MVa area. There was a negative correlation between MVa area and the
      percentage by which the MVL area exceeded the MVa area. Anterior MVLs had a
      significantly higher number of chordae tendineae than did posterior MVLs.
      Histologically, layering of MVLs was less preserved in the distal segment,
      whereas the muscular component and adipose tissue were significantly more diffuse
      in the proximal and middle segments. CONCLUSIONS AND CLINICAL RELEVANCE: The MV
      in cardiologically normal dogs had wide anatomic variability. Anatomic
      measurements of MVL length were correlated with echocardiographic measurements.

PMID- 21879977
TI  - Influence of electrode position on cardioversion energy requirements during
      transvenous electrical cardioversion in horses.
AB  - OBJECTIVE: To evaluate influence of electrode position on cardioversion energy
      (CE; energy delivered in the shock at which cardioversion was achieved) during
      transvenous electrical cardioversion (TVEC) in horses with atrial fibrillation.
      ANIMALS: 37 horses with atrial fibrillation (41 cardioversion events).
      PROCEDURES: Records were reviewed to identify horses that underwent TVEC for
      treatment of atrial fibrillation. Signalment and CE were recorded. Electrode
      positions in the right atrium and pulmonary artery were identified on
      intraoperative radiographs. An orthogonal coordinate space was created, and
      electrode y- and z-axis coordinates and shadow lengths were determined.
      Trigonometric modeling was used to estimate x-axis electrode positions that
      resulted in observed shadows. Postmortem casts of catheterized horses were used
      to assess electrode paths and anatomic relationships. Model assumptions were
      tested by use of these and a theoretical data set. Relationships between
      signalment, electrode position, and CE were assessed via multivariate analysis.
      RESULTS: Sex and y-axis differences between electrode positions were significant
      predictors of CE. Population stratification based on examination of residuals
      improved model strength; populations differed in z-axis variables and in CE.
      Decreasing distance between electrodes and pulmonary artery electrode positions
      ventral to the right atrium were associated with increased CE. Agreement between
      estimated and actual x-axis coordinates was poor. CONCLUSIONS AND CLINICAL
      RELEVANCE: Optimal electrode positioning can reduce the energy requirement for
      successful TVEC and may eventually support application of TVEC under short-term
      IV anesthesia and potentially increase chances of treatment response. Further
      investigation into these relationships is warranted.

PMID- 21879978
TI  - Effect of hematocrit on accuracy of two point-of-care glucometers for use in
      dogs.
AB  - OBJECTIVE: To determine the effect of Hct on blood glucose readings of dogs
      obtained by use of 2 point-of-care (POC) blood glucometers and a laboratory
      analyzer. ANIMALS: 184 dogs, including 139 Greyhounds. PROCEDURES: Venous blood
      samples collected from 184 dogs with a range of Hcts (measured in EDTA
      anticoagulated blood) were immediately analyzed with a handheld glucometer
      specifically developed for veterinary use and a glucometer developed for use in
      humans. The remainder of each blood sample was placed in fluoride oxalate tubes,
      and plasma glucose concentration was measured with a laboratory analyzer.
      Agreement between results for the POC glucometers and laboratory analyzer and
      effect of Hct on glucometer accuracy was assessed via regression analysis.
      RESULTS: Significant differences were detected between results of the glucometers
      and the reference laboratory analyzer. The Hct affected the correlation between
      results for the glucometers and the laboratory analyzer. Deviations of the
      glucometers from the reference interval varied with Hct. The glucometer for
      veterinary use more closely correlated with the glucose concentration when Hct
      was within or above its reference interval. The glucometer for use in humans more
      closely approximated laboratory reference glucose concentrations in anemic dogs.
      CONCLUSIONS AND CLINICAL RELEVANCE: Hct had a relevant impact on the correlation
      between whole blood and plasma glucose concentrations in dogs. Significant
      variations between results obtained with the 2 glucometers could be critical when
      interpreting blood glucose measurements or selecting a POC glucometer for an
      intensive care setting and precise glycemic control in critically ill dogs.

PMID- 21879979
TI  - Comparison of cross-sectional anatomy and computed tomography of the tarsus in
      horses.
AB  - OBJECTIVE: To compare computed tomography (CT) images of equine tarsi with cross
      sectional anatomic slices and evaluate the potential of CT for imaging
      pathological tarsal changes in horses. SAMPLE: 6 anatomically normal equine
      cadaveric hind limbs and 4 tarsi with pathological changes. PROCEDURES:
      Precontrast CT was performed on 3 equine tarsi; sagittal and dorsal
      reconstructions were made. In all limbs, postcontrast CT was performed after
      intra-articular contrast medium injection of the tarsocrural, centrodistal, and
      tarsometatarsal joints. Images were matched with corresponding anatomic slices.
      Four tarsi with pathological changes underwent CT examination. RESULTS: The
      tibia, talus, calcaneus, and central, fused first and second, third, and fourth
      tarsal bones were clearly visualized as well as the long digital extensor,
      superficial digital flexor, lateral digital flexor (with tarsal flexor
      retinaculum), gastrocnemius, peroneus tertius, and tibialis cranialis tendons and
      the long plantar ligament. The lateral digital extensor, medial digital flexor,
      split peroneus tertius, and tibialis cranialis tendons and collateral ligaments
      could be located but not always clearly identified. Some small tarsal ligaments
      were identifiable, including plantar, medial, interosseus, and lateral
      talocalcaneal ligaments; interosseus talocentral, centrodistal, and
      tarsometatarsal ligaments; proximal and distal plantar ligaments; and
      talometatarsal ligament. Parts of the articular cartilage could be assessed on
      postcontrast images. Lesions were detected in the 4 tarsi with pathological
      changes. CONCLUSIONS AND CLINICAL RELEVANCE: CT of the tarsus is recommended when
      radiography and ultrasonography are inconclusive and during preoperative planning
      for treatment of complex fractures. Images from this study can serve as a CT
      reference, and CT of pathological changes was useful.

PMID- 21879980
TI  - Effect of sedation protocol on glomerular filtration rate in cats as determined
      by use of quantitative renal scintigraphy.
AB  - OBJECTIVE: To evaluate the effect of several sedation protocols on glomerular
      filtration rate (GFR) in cats as measured by use of quantitative renal
      scintigraphy and to analyze interobserver differences in GFR calculation.
      ANIMALS: 5 cats (1 sexually intact male, 1 neutered male, and 3 sexually intact
      females). PROCEDURES: Effects on GFR of 3 sedation protocols commonly used at the
      Iowa State University College of Veterinary Medicine were evaluated. The
      protocols were medetomidine (11 MUg/kg) and butorphanol tartrate (0.22 mg/kg)
      administered i.m.; ketamine hydrochloride (10 mg/kg) and midazolam (0.5 mg/kg)
      administered i.v.; and ketamine (10 mg/kg), midazolam (0.5 mg/kg), and
      acepromazine maleate (0.05 mg/kg) administered i.m.. Results for the 3 protocols
      were compared with results of GFR measurements obtained in these same cats
      without sedation (control protocol). RESULTS: No significant difference between
      GFR measurements was associated with the 3 sedation protocols, compared with GFR
      measurements for the control protocol. The greatest mean GFR values were for the
      medetomidine-butorphanol and ketamine-midazolam protocols. There were no
      significant differences between observers for calculation of GFR. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that none of the 3 sedation protocols had
      significant effects on GFR calculated by use of quantitative renal scintigraphy,
      compared with results for GFR evaluations performed in the cats when they were
      not sedated. No significant interobserver error was evident. However, the
      statistical power of this study was low, and the probability of a type II error
      was high.

PMID- 21879981
TI  - Nutritional analysis of gastric contents and body condition score at a single
      time point in feral horses in Australia.
AB  - OBJECTIVE: To determine the impact of a free-choice diet on nutritional intake
      and body condition of feral horses. ANIMALS: Cadavers of 41 feral horses from 5
      Australian locations. PROCEDURES: Body condition score (BCS) was determined
      (scale of 1 to 9), and the stomach was removed from horses during postmortem
      examination. Stomach contents were analyzed for nutritional variables and
      macroelement and microelement concentrations. Data were compared among the
      locations and also compared with recommended daily intakes for horses. RESULTS:
      Mean BCS varied by location; all horses were judged to be moderately thin. The
      BCS for males was 1 to 3 points higher than that of females. Amount of protein in
      the stomach contents varied from 4.3% to 14.9% and was significantly associated
      with BCS. Amounts of water-soluble carbohydrate and ethanol-soluble carbohydrate
      in stomach contents of feral horses from all 5 locations were higher than those
      expected for horses eating high-quality forage. Some macroelement and
      microelement concentrations were grossly excessive, whereas others were grossly
      deficient. There was no evidence of ill health among the horses. CONCLUSIONS AND
      CLINICAL RELEVANCE: Results suggested that the diet for several populations of
      feral horses in Australia appeared less than optimal. However, neither low BCS
      nor trace mineral deficiency appeared to affect survival of the horses.
      Additional studies on food sources in these regions, including analysis of water
      soluble carbohydrate, ethanol-soluble carbohydrate, and mineral concentrations,
      are warranted to determine the provenance of such rich sources of nutrients.
      Determination of the optimal diet for horses may need revision.

PMID- 21879982
TI  - Pharmacokinetics of intra-articular, intravenous, and intramuscular
      administration of triamcinolone acetonide and its effect on endogenous plasma
      hydrocortisone and cortisone concentrations in horses.
AB  - OBJECTIVE: To compare pharmacokinetics of triamcinolone acetonide (TA) following
      i.v., intra-articular (i.a.), and i.m. administration and determine its effect on
      plasma concentrations of hydrocortisone and cortisone. ANIMALS: 6 Thoroughbreds.
      PROCEDURES: TA (0.04 mg/kg) was administered i.v., i.m., or i.a., and plasma TA,
      hydrocortisone, and cortisone concentrations were determined. RESULTS: I.v.
      administration of TA was fitted to a 2-compartment model. Median distribution
      half-life was 0.50 hours (range, 0.24 to 0.67 hours); elimination half-life was
      6.1 hours (range, 5.0 to 6.4 hours). Transfer half-life of TA from joint to
      plasma was 5.2 hours (range, 0.49 to 73 hours); elimination half-life was 23.8
      hours (range, 18.9 to 32.2 hours). Maximum plasma concentration following i.a.
      administration was 2.0 ng/mL (range, 0.94 to 2.5 ng/mL), and was attained at 10
      hours (range, 8 to 12 hours). Maximum plasma concentration following i.m.
      administration was 0.34 ng/mL (range, 0.20 to 0.48 ng/mL) and was attained at
      13.0 hours (range, 12 to 16 hours); concentration was still quantifiable at 360
      hours. Hydrocortisone plasma concentrations were significantly different from
      baseline within 0.75, 2, and 1 hours after i.v., i.a., and i.m. administration,
      respectively, and remained significantly different from baseline at 96 and 264
      hours for i.v. and i.a. administration. Following i.m. administration of TA,
      plasma concentrations of hydrocortisone did not recover to baseline
      concentrations by 360 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetics
      of TA and related changes in hydrocortisone were described following i.v., i.a.,
      and i.m. administration. A single administration of TA has profound effects on
      secretion of endogenous hydrocortisone.

PMID- 21879983
TI  - Evaluation of the in vitro activity of gallium nitrate against Mycobacterium
      avium subsp paratuberculosis.
AB  - OBJECTIVE: To evaluate the in vitro susceptibility of various field isolates of
      Mycobacterium avium subsp paratuberculosis (MAP) to gallium nitrate. SAMPLE: 10
      isolates of MAP, including 4 isolated from cattle, 2 isolated from bison, 1
      isolated from an alpaca, and 3 isolated from humans. PROCEDURES: The in vitro
      susceptibility to gallium nitrate was tested by use of broth culture with
      detection of MAP growth by means of a nonradiometric automated detection method.
      For each MAP isolate, a series of 7 dilutions of gallium nitrate (concentrations
      ranging from 200 to 1,000 MUM) were tested. Gallium nitrate was considered to
      have caused 90% and 99% inhibition of the MAP growth when the time to detection
      for culture of the MAP stock solution and a specific concentration of gallium
      nitrate was delayed and was similar to that obtained for culture of the MAP stock
      solution (without the addition of gallium nitrate) diluted 1:10 and 1:100,
      respectively. RESULTS: Gallium nitrate inhibited MAP growth in all 10 isolates.
      The susceptibility to gallium nitrate was variable among isolates, and all
      isolates of MAP were inhibited in a dose-dependent manner. Overall, the
      concentration that resulted in 90% inhibition ranged from < 200 MUM for the most
      susceptible isolates to 743 MUM for the least susceptible isolates. CONCLUSIONS
      AND CLINICAL RELEVANCE: Gallium nitrate had activity against all 10 isolates of
      MAP tested in vitro and could potentially be used as a prophylactic agent to aid
      in the control of MAP infections during the neonatal period.

PMID- 21879984
TI  - Pharmacokinetics of levetiracetam after oral and intravenous administration of a
      single dose to clinically normal cats.
AB  - OBJECTIVE: To determine whether therapeutic concentrations of levetiracetam can
      be achieved in cats and to establish reasonable i.v. and oral dosing intervals
      that would not be associated with adverse effects in cats. ANIMALS: 10 healthy
      purpose-bred cats. PROCEDURES: In a randomized crossover study, levetiracetam (20
      mg/kg) was administered orally and i.v. to each cat. Blood samples were collected
      0, 10, 20, and 40 minutes and 1, 1.5, 2, 3, 4, 6, 9, 12, and 24 hours after
      administration. Plasma levetiracetam concentrations were determined via high
      performance liquid chromatography. RESULTS: Mean +/- SD peak concentration was
      25.54 +/- 7.97 MUg/mL. The mean y-intercept for i.v. administration was 37.52 +/-
      6.79 MUg/mL. Half-life (harmonic mean +/- pseudo-SD) was 2.95 +/- 0.95 hours and
      2.86 +/- 0.65 hours for oral and i.v. administration, respectively. Mean volume
      of distribution at steady state was 0.52 +/- 0.09 L/kg, and mean clearance was
      2.0 +/- 0.60 mL/kg/min. Mean oral bioavailability was 102 +/- 39%. Plasma drug
      concentrations were maintained in the therapeutic range reported for humans (5 to
      45 MUg/mL) for at least 9 hours after administration in 7 of 10 cats. Only mild,
      transient hypersalivation was evident in some cats after oral administration.
      CONCLUSIONS AND CLINICAL RELEVANCE: Levetiracetam (20 mg/kg) administered orally
      or i.v. to cats every 8 hours should achieve and maintain concentrations within
      the therapeutic range for humans. Levetiracetam administration has favorable
      pharmacokinetics for clinical use, was apparently tolerated well, and may be a
      reasonable alternative antiepileptic drug in cats.

PMID- 21879985
TI  - Ultrasonographic evaluation of postprandial heart variation in juvenile Paraguay
      anacondas (Eunectes notaeus).
AB  - OBJECTIVE: To noninvasively evaluate physiologic postprandial adaptations of the
      heart in snakes. ANIMALS: 6 juvenile Paraguay anacondas (Eunectes notaeus).
      PROCEDURES: The heart of each anaconda was echocardiographically evaluated after
      food was withheld for 28 days as well as 3 and 10 days after feeding. Physical
      measurements included body length, weight, and circumference at the level of the
      heart. Echocardiographic measurements included heart rate and 2-D total and
      internal ventricular area. From these measurements, total ventricular volume as
      well as the myocardial area as a surrogate of myocardial mass was calculated.
      RESULTS: No significant changes in body length, weight, and circumference were
      found. Significant increases in heart rate (from 45 to 58 beats/min), total
      ventricular volume (from 4.63 to 5.54 mL), and myocardial area (from 0.7 to 0.81
      cm(2)) were detected 10 days after feeding, compared with results obtained prior
      to feeding after food had been withheld for 28 days. No pericardial effusion was
      detected at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Echocardiographic
      evaluation of the heart of anacondas was performed, and feeding resulted in
      concentric cardiac hypertrophy. Physiologic fluctuation of cardiac dimensions
      should be considered when cardiac imaging is performed in snakes.

PMID- 21879986
TI  - Effect of omega-3 fatty acids on serum concentrations of adipokines in healthy
      cats.
AB  - OBJECTIVE: To determine associations between serum concentrations of omega-3
      polyunsaturated fatty acids and concentrations of adiponectin, leptin, and
      insulin in healthy cats. ANIMALS: 56 healthy adult client-owned cats. PROCEDURES:
      Body condition score (BCS) was determined, and blood samples were collected after
      food was withheld for 12 hours. Serum was harvested for fatty acid analysis and
      measurement of serum concentrations of adiponectin, leptin, insulin, glucose,
      triglyceride, and cholesterol. RESULTS: 1 cat was removed because of
      hyperglycemia. Significant interaction effects between BCS and serum
      concentrations of eicosapentaenoic acid (EPA) were detected for the analyses of
      associations between EPA and serum concentrations of adiponectin, insulin, and
      triglyceride. Cats were categorized into nonobese (BCS, 4 to 6 [n = 34 cats]) and
      obese (BCS, 7 to 8 [21]) groups; serum concentrations of EPA were directly
      associated with concentrations of adiponectin and inversely associated with
      concentrations of insulin and triglyceride in obese cats and were directly
      associated with concentrations of leptin and inversely associated with
      concentrations of adiponectin in nonobese cats. Additionally, serum
      concentrations of docosahexaenoic acid were directly associated with
      concentrations of adiponectin in obese cats. No significant associations between
      serum concentrations of docosahexaenoic acid or alpha-linolenic acid were
      detected in the analyses for all cats. Female cats had higher serum
      concentrations of adiponectin and lower concentrations of glucose than did male
      cats. Increased age was associated with a small increase in serum concentrations
      of leptin. CONCLUSIONS AND CLINICAL RELEVANCE: EPA may ameliorate the decrease in
      adiponectin and the increase in insulin and triglyceride concentrations in obese
      cats.

PMID- 21879987
TI  - Effects of hyperbaric oxygen treatment on horses with experimentally induced
      endotoxemia.
AB  - OBJECTIVE: To determine the effectiveness of preinduction hyperbaric oxygen
      treatment (HBOT) in ameliorating signs of experimentally induced endotoxemia in
      horses. ANIMALS: 18 healthy adult horses. PROCEDURES: Horses were randomly
      assigned to 1 of 3 equal-sized treatment groups to receive normobaric ambient air
      and lipopolysaccharide (LPS), HBOT and LPS, or HBOT and physiologic saline (0.9%
      NaCl) solution. Horses were physically examined, and blood was obtained for a CBC
      and to determine concentration or activity of plasma tissue necrosis factor
      alpha, blood lactate, and blood glucose before the horses were treated with HBOT
      and then intermittently for 6 hours after administration of LPS or physiologic
      saline solution. RESULTS: All LPS-treated horses developed signs and biochemical
      and hematologic changes consistent with endotoxemia. Treatment with HBOT
      significantly ameliorated the effect of LPS on clinical endotoxemia score but did
      not significantly improve other abnormalities associated with endotoxemia.
      CONCLUSIONS AND CLINICAL RELEVANCE: The protective effect of HBOT was minimal,
      and results did not support its use as a treatment for horses prior to
      development of endotoxemia.

PMID- 21879989
TI  - Tactile and thermal detection thresholds of the scalp skin.
AB  - The tactile and thermal sensitivity of diverse regions of the human body have
      been documented extensively, with one exception being the scalp. Additionally,
      sensory changes may accompany the hair loss from the scalp in androgen-related
      alopecia (ARA), but formal quantitative sensory testing (QST) has not been
      reported in respect of this. Therefore, light touch detection thresholds were
      obtained at nine scalp sites and one forehead site, using Semmes-Weinstein
      filaments (Von Frey hairs), and for warming and cooling from skin baseline
      temperature, using 28 and 256 mm(2) thermodes. Affective, thermal, and
      nociceptive sensations experienced at thermal detection threshold were
      quantified. Thirty-two male participants were recruited, 10 of whom had normal
      hair coverage, 12 of whom had shaved scalp but with potentially normal hair
      coverage, and 10 of whom exhibited ARA to some extent. The scalp was relatively
      insensitive to tactile and thermal stimulation at all tested sites, especially so
      along the midline and near the apex of the skull. Threshold level warm stimuli
      were rated less pleasant, the less sensitive the test site. After correction for
      age-related changes in sensitivity, bald scalp sites were found more sensitive to
      cooling than the same sites when shaved, consistent with prior informal reports
      of increased sensitivity for some scalp sensations in ARA. QST on hair-covered
      sites was subject to methodological issues that render such testing non-ideal,
      such as bias in measurement of resting skin temperatures, and the near
      impossibility of delivering filament stimuli to the scalp skin without disturbing
      neighboring hairs.

PMID- 21879988
TI  - Evaluation of glomerular filtration rate by use of dynamic computed tomography
      and Patlak analysis in clinically normal cats.
AB  - OBJECTIVE: To obtain quantitative variables of the abdominal aorta and both
      kidneys on the basis of time-attenuation curves (TACs) and to measure glomerular
      filtration rate (GFR) for each kidney and the global GFR in clinically normal
      cats by use of dynamic computed tomography (CT) and Patlak analysis. ANIMALS: 9
      healthy cats. PROCEDURES: All the cats were anesthetized with propofol.
      Anesthesia was maintained by administration of isoflurane, and CT examination was
      performed in the anesthetized cats. The TACs and renal volume were measured by
      use of the baseline precontrast and single-slice dynamic scans. The CT-GFR of
      each kidney and the global CT-GFRs were calculated via Patlak plot analysis.
      RESULTS: CT-GFR results from 7 cats were valid. Peak aortic enhancement was
      detected between 9.0 and 14.0 seconds after iohexol injection, and the initial
      peak time of renal parenchymal enhancement was 15 to 24 seconds after iohexol
      injection. Mean +/- SD global GFR was 2.06 +/- 0.62 mL/min/kg. Mean +/- SD CT-GFR
      of the right and left kidneys was 0.97 +/- 0.32 mL/min/kg and 1.05 +/- 0.31
      mL/min/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The CT-GFR method
      can be rapidly and conveniently performed in clinically normal cats. This
      combined structural-functional approach provided physiologic and morphological
      information on the kidneys of cats.

PMID- 21879990
TI  - Characteristics of synaptic connections between rodent primary somatosensory and
      motor cortices.
AB  - The reciprocal connections between primary motor (M1) and primary somatosensory
      cortices (S1) are hypothesized to play a crucial role in the ability to update
      motor plans in response to changes in the sensory periphery. These interactions
      provide M1 with information about the sensory environment that in turn signals S1
      with anticipatory knowledge of ongoing motor plans. In order to examine the
      synaptic basis of sensorimotor feedforward (S1-M1) and feedback (M1-S1)
      connections directly, we utilized whole-cell recordings in slices that preserve
      these reciprocal sensorimotor connections. Our findings indicate that these
      regions are connected via direct monosynaptic connections in both directions.
      Larger magnitude responses were observed in the feedforward direction (S1-M1),
      while the feedback (M1-S1) responses occurred at shorter latencies. The
      morphology as well as the intrinsic firing properties of the neurons in these
      pathways indicates that both excitatory and inhibitory neurons are targeted.
      Differences in synaptic physiology suggest that there exist specializations
      within the sensorimotor pathway that may allow for the rapid updating of sensory
      motor processing within the cortex in response to changes in the sensory
      periphery.

PMID- 21879991
TI  - Using the Rose Angina Questionnaire cross-culturally: the importance of
      consulting lay people when translating epidemiological questionnaires.
AB  - OBJECTIVES: The Rose Angina Questionnaire (RAQ) is an important measure of
      coronary heart disease prevalence. It has been shown to perform inconsistently
      across some ethnic groups in Britain. This study investigates whether the best
      available versions of the RAQ in Punjabi and Cantonese were linguistically
      equivalent to the English version. DESIGN: Interviews were carried out with lay
      people from the Pakistani, Chinese and European-origin communities in Scotland to
      assess the versions of the RAQ used in the Newcastle Heart Project (the best
      available versions). For each questionnaire item, participants were asked to
      elaborate on their understanding of the question and the meaning of keywords or
      phrases. RESULTS: Problems were discovered with the Punjabi and Cantonese
      translations of the RAQ. For example, the translation for 'chest' was interpreted
      by some Pakistani and Chinese women to mean 'breasts'. 'Walking uphill' was
      translated in Chinese as 'walking the hill', without stipulation of the
      direction, so that some Cantonese speakers interpreted the question as pertaining
      to walking downhill. Many Chinese interpreted RAQ items to be referring to
      breathlessness rather than chest pain due to ambiguous wording. CONCLUSION:
      Existing versions of the RAQ are unlikely to be yielding data that are cross
      culturally valid or comparable. For robust health survey research in languages
      other than that in which the questionnaire was developed, lay assessment of
      questionnaires prior to and after translation is a necessity rather than a
      luxury.

PMID- 21879992
TI  - Characterization and classification of psittacine atherosclerotic lesions by
      histopathology, digital image analysis, transmission and scanning electron
      microscopy.
AB  - Atherosclerosis is a degenerative and inflammatory vascular disease characterized
      in mammals and birds by the accumulation of inflammatory cells, lipids, calcium,
      and formation of large fibrofatty lesions within the intima of arteries resulting
      in the disorganization of the arterial wall and stenosis of the lumen. Despite
      the high incidence of atherosclerosis in parrots and the high number of case
      reports, there are few pathologic investigations and the ultrastructural study of
      the lesions has not been documented. Sixty-three major arteries were collected
      from 24 psittacine birds of 11 species during routine post-mortem examinations.
      Samples from the major arteries were fixed in 2% paraformaldehyde and 1.25%
      glutaraldehyde, and processed for transmission electron microscopy (TEM) and
      scanning electron microscopy (SEM). Additional samples were fixed in 10% formalin
      and embedded in paraffin for histological examination. Additional histochemical
      stains for calcium, elastic fibres, and lipid were performed. Toluidine blue
      stained 0.5 um-thick resin sections were also obtained. Digital image analysis
      was performed to provide objective quantitative information on the different
      lesions. The histopathology and ultrastructure of psittacine atherosclerosis were
      found to be similar to other avian and mammalian species. Seven lesion types
      could be described, which were similar to the human classification system.
      Digital image analysis, TEM, and SEM helped to further describe the lesions and
      refine the classification system. TEM findings were similar to other avian and
      mammalian species with the notable presence of macrophage-derived and smooth
      muscle cell-derived foam cells and extracellular lipid. SEM revealed various
      stages of endothelial surface defects and, occasionally, adherent blood cells.

PMID- 21879993
TI  - Brain stimulation improves associative memory in an individual with amnestic mild
      cognitive impairment.
AB  - In patients with cognitive deficits, brain stimulation has been shown to restore
      cognition ( Miniussi et al., 2008 , Brain Stimulation, 1, 326). The aim of this
      study was to assess whether repetitive Transcranial Magnetic Stimulation (rTMS)
      could improve memory performance in an individual with amnestic Mild Cognitive
      Impairment (aMCI). Stimulation of the left parietal cortex increased accuracy in
      an association memory task, and this improvement was still significant 24 weeks
      after stimulation began. These findings indicate that rTMS to the left parietal
      cortex improved memory performance in aMCI.

PMID- 21879994
TI  - Structural and functional neuroimaging methods in the diagnosis of dementias: a
      retrospective chart and brain imaging review.
AB  - OBJECTIVE: Assess the contribution of structural and functional neuroimaging
      methods to the diagnosis of dementia. METHODS: This was a retrospective chart and
      imaging review. Participants were 24 inpatient dementia cases from a general
      hospital-based, university medical psychiatry unit. Data from clinical charts and
      imaging results were reviewed. RESULTS: Most common initial diagnoses were
      dementia NOS and vascular dementia (VD); most common discharge diagnoses were VD,
      Alzheimer's, Dementia NOS and dementia with Lewy bodies. Most diagnostic changes
      occurred following family meetings or SPECT/PET, with fewer changes after CT/MRI.
      CONCLUSIONS: Diagnostic steps that contributed the most to the final diagnosis
      were the family meeting and the functional neuroimaging evaluation.

PMID- 21879995
TI  - Grammar disruption in a patient with Neuro-Sweet syndrome.
AB  - This paper for the first time reports detailed neurolinguistic findings in a
      patient with Neuro-Sweet syndrome. In this patient the presenting symptoms of
      central nervous system (CNS) involvement primarily consisted of a selective
      grammar deficit restricted to spontaneous speech. On MRI a left prefrontal
      ischemic stroke (superior part BA 6) and two small subcortical left parietal
      infarctions were found. Neurolinguistic analyses, however, did not reveal a
      profile consistent with any observations of agrammatism caused by structural
      damage to the language areas critically involved in grammatical processing. It is
      hypothesized that selectively distorted grammar might reflect disruption of the
      frontosubcortical network involved in language processing. Prefrontal
      neurobehavioral abnormalities associated with functional disruption of the
      inferior medial frontal regions as demonstrated by SPECT, additionally suggest
      that agrammatic symptoms may be linked to a higher-level cognitive disorder
      following encephalopathic CNS involvement.

PMID- 21879998
TI  - Is it time for permissive hypoxaemia in the intensive care unit?

PMID- 21879999
TI  - Permissive hypercapnia in acute respiratory distress syndrome - is now the time
      to get strict?

PMID- 21879996
TI  - A case of frontal neuropsychological and neuroimaging signs following multiple
      primary-blast exposure.
AB  - Blast-related traumatic brain injury (TBI) from the Afghanistan and Iraq wars
      represents a significant medical concern for troops and veterans. To better
      understand the consequences of primary-blast injury in humans, we present a case
      of a Marine exposed to multiple primary blasts during his 14-year military
      career. The neuropsychological profile of this formerly high-functioning veteran
      suggested primarily executive dysfunction. Diffusion-tensor imaging revealed
      white-matter pathology in long fiber tracks compared with a composite fractional
      anisotropy template derived from a veteran reference control group without TBI.
      This study supports the existence of primary blast-induced neurotrauma in humans
      and introduces a neuroimaging technique with potential to discriminate multiple
      blast TBI.

PMID- 21880000
TI  - The predictive ability of a weighted systemic inflammatory response syndrome
      score for microbiologically confirmed infection in hospitalised patients with
      suspected sepsis.
AB  - BACKGROUND: The systemic inflammatory response syndrome (SIRS) concept lacks
      sensitivity and specificity for guiding clinical practice and sepsis research.
      OBJECTIVE: To assess the performance of a weighted SIRS score, with emphasis on
      white cell count and temperature criteria in predicting microbiologically
      confirmed infection. DESIGN AND SETTING: Prospective cohort study at Princess
      Alexandra Hospital, a tertiary teaching hospital in Queensland, Australia.
      PARTICIPANTS: Patients aged 18 years or older who were hospitalised with
      suspected infection and started on antimicrobial therapy. MAIN OUTCOME MEASURES:
      The utility of each SIRS criterion, the 1992 consensus conference recommendation
      (<= 2 SIRS criteria) and a weighted SIRS score in predicting microbiologically
      confirmed infection were compared. RESULTS: 2085 patients were included in the
      analysis. All criteria performed poorly, with low sensitivities (27.3%-70.6%),
      low specificities (37.5%-77.5%), low positive predictive values (61.5%-65.3%),
      low negative predictive values (39.8%-45.1%), and likelihood ratios close to 1.0.
      Both SIRS and weighted SIRS scores did not perform better than clinicians'
      suspicion for infection. CONCLUSIONS: Both SIRS and weighted SIRS score had low
      predictive ability for microbiologically confirmed infection. A more robust
      conceptual framework incorporating clinical, biochemical and immunological
      markers must be formulated and validated to better guide clinical practice and
      research. Clinicians' suspicions may be as good as any scoring system at
      identifying patients with infection and sepsis.

PMID- 21880001
TI  - Comparison of central venous pressure and venous oxygen saturation from venous
      catheters placed in the superior vena cava or via a femoral vein: the numbers are
      not interchangeable.
AB  - OBJECTIVE: To compare venous pressure and haemoglobin oxygen saturation measured
      from a catheter in the superior vena cava (SVC) with a catheter inserted via the
      femoral vein, and to assess the agreement of these measurements. To assess the
      effect of intra-abdominal pressure and intrathoracic pressures on these
      measurements. DESIGN, SETTING AND PARTICIPANTS: Prospective study of patients in
      an adult intensive care unit, Alfred Hospital, Melbourne, Australia. MAIN OUTCOME
      MEASURES: Central venous pressure (CVP), femoral venous pressure (FVP), venous
      haemoglobin oxygen saturation in the SVC (SO2C) and via the femoral vein (SO2F),
      agreement between these measures using the Bland-Altman method, and the effect of
      intra-abdominal pressure and intrathoracic pressure. RESULTS: 43 patients were
      included; the mean bias for FVP -CVP was 1.05 mmHg (95% CI, 0.30-1.79 mmHg), with
      limits of agreement of -3.79 to 5.89 mmHg (95% CI, -5.08 to 7.18 mmHg). The bias
      for SO2F -SO2C was -3.21 (95% CI, -6.33 to -0.10), with limits of agreement of 
      22.43 to 16.01 (95% CI, -27.81 to 21.39). Intra-abdominal pressure had a
      significant (P < 0.01) effect on both the FVP and on the difference (FVP -CVP).
      CONCLUSIONS: This study demonstrates poor agreement between CVP and FVP and
      between SO2C and SO2F and that the measurements taken from these two sites are
      not interchangeable clinically.

PMID- 21880002
TI  - A pilot study of the epidemiology and associations of pulse pressure variation
      among non-cardiac surgery critically ill patients.
AB  - BACKGROUND: A pulse pressure variation (PPV) >= 13% of mean arterial pressure
      (MAP) is an accepted marker of a fluid-responsive state. However, there is no
      study of its epidemiology and associations among non-cardiac critically ill
      patients. OBJECTIVES: To conduct a pilot study of the epidemiology and
      associations of a PPV >= 13% among non-cardiac critically ill patients. DESIGN:
      Prospective observational study. SETTING: Intensive care unit of a university
      hospital. PATIENTS: Cohort of 37 sedated critically ill patients undergoing
      mandatory ventilation. MAIN OUTCOME MEASURES: PPV values, tidal volume and peak
      airway pressure, MAP, heart rate (HR) and central venous pressure (CVP) collected
      every 15 minutes; fluid balance collected hourly; correlation between PPV and
      these variables. RESULTS: 450 PPV measurements were collated. The PPV value was
      >= 13% in 86 (19%) measurements and was observed in two consecutive measurements
      in 68 (15%) of cases. On multivariable analysis, mean PPV was significantly
      correlated with CVP (P=0.04), HR (P<0.001) and peak airway pressure (P=0.001),
      but not fluid balance (P=0.3). CONCLUSIONS: Among non-cardiac surgery
      mechanically ventilated patients, a PPV in the fluid-responsive range was present
      in one-fifth of measurements and showed logical correlations with relevant
      haemodynamic and mechanical ventilation-related variables. Our results provide a
      rationale for a more comprehensive evaluation of PPV measurement in suitable
      critically ill patients.

PMID- 21880003
TI  - Antecedents to cardiac arrests in a hospital equipped with a medical emergency
      team.
AB  - BACKGROUND: Studies conducted before the conception of medical emergency teams
      (METs) revealed that cardiac arrests were often preceded by deranged vital signs.
      METs have been implemented in hospitals to review ward patients whose conditions
      are deteriorating in order to prevent adverse events, including cardiac arrest.
      Antecedents to cardiac arrests in a MET-equipped hospital have not been assessed.
      OBJECTIVES: To determine what proportion of patients who had cardiac arrests had
      documented MET criteria before the arrest, and what proportion had a premorbid
      status suggesting they were unsuitable resuscitation candidates. DESIGN AND
      SETTING: Prospective observational study of cardiac arrests at the Austin
      Hospital, Melbourne, Australia, 1 April - 30 September 2010. Data were obtained
      from the patients' records and electronic "respond blue" database. MAIN OUTCOME
      MEASURES: Patients' premorbid medical condition and functional status; prior "not
      for-resuscitation" (NFR) order; presence or absence of a MET call before cardiac
      arrest; time and rhythm of cardiac arrest; and in hospital mortality. RESULTS: 27
      patients had a cardiac arrest during the study period, 22 of whom had no prior
      documented NFR order. Among these 22 patients, 18 (82%) had an initial rhythm of
      asystole or pulseless electrical activity, and 16 (73%) died in hospital. Fifty
      per cent of arrests were detected between midnight and 08:00. All six patients
      classified as unsuitable resuscitation candidates died in hospital, and there
      were trends for increased age and poorer functional status when compared with
      suitable candidates. A further six patients had documented MET criteria in the 6
      hours before the arrest, but did not receive MET review. CONCLUSIONS: In this 6
      month audit, about half the patients with cardiac arrest may have been unsuitable
      for resuscitation, or had objective warning signs that were not acted on. Further
      improvements in advanced care planning and optimisation of MET activation may
      further reduce cardiac arrest calls at our hospital.

PMID- 21880004
TI  - A retrospective cohort study of the effect of medical emergency teams on
      documentation of advance care directives.
AB  - OBJECTIVE: To describe the longitudinal changes in documentation of advance care
      directives (ACDs), including limitation of medical therapy (LMT) and not-for
      resuscitation (NFR) directives among patients reviewed by a medical emergency
      team (MET). DESIGN AND SETTING: Single-centre, retrospective cohort study at a
      tertiary teaching hospital in Wellington, New Zealand, from 1 October 2009 to 30
      September 2010. PARTICIPANTS: Adult surgical and medical inpatients attended by
      the hospital's MET, which attends medical emergency calls and cardiac arrest
      calls. MAIN OUTCOME MEASURES: Chronology of LMT and NFR documentation rates in
      relation to hospital admission and MET attendance. Medical compliance with
      hospital NFR documentation policy. Differences in characteristics and outcomes of
      patients with and without documented ACDs. RESULTS: Documentation of LMT and NFR
      directives at admission was low (18%) in the 71 patient files included in the
      study. The LMT and NFR directive documentation rate before MET review (32%)
      doubled after MET involvement (62%). Universal NFR directive documentation was
      not achieved (66% NFR rate). Presence of pre-MET ACDs were associated with
      increased age, but this group had similar comorbidities and mortality rates to
      the group without directives. Presence of ACD documentation after MET review was
      associated with increased age, comorbidity burden and in hospital mortality.
      CONCLUSIONS: Compliance with hospital policy of universal documentation was low
      despite MET involvement. There was a strong association between ACDs and death,
      suggesting an opt-out culture. Further investigation is needed into the
      interaction between hospital systems, medical culture, human factors, and patient
      centred clinical decision making.

PMID- 21880005
TI  - Medical reviews before cardiac arrest, medical emergency call or unanticipated
      intensive care unit admission: their nature and impact on patient outcome.
AB  - OBJECTIVE: To measure and describe the extent and consequences of documented
      medical patient reviews in the 24 hours before a cardiac arrest, medical
      emergency team (MET) call or an unanticipated intensive care unit admission
      ("event"), and the use of such reviews as a rapid response system performance
      measure. DESIGN: Retrospective case-note and database review. SETTING: Tertiary
      referral hospital, April-September, 2008. PARTICIPANTS: Adult inpatients who had
      an event and a preceding hospital length of stay > 24 hours. MAIN OUTCOME
      MEASURES: Hospital discharge status, ICU length of stay, not-for-resuscitation
      order. RESULTS: 443 patients had 575 events (6.1% cardiac arrests, 68.7% MET
      calls, 25.2% ICU admissions) in the study period. A documented medical review
      preceded 561 (97.6%) events. Patients whose review was a home team review (HTR;
      ie, from a general ward) only were older than those with a critical care review
      (CCR) (70.2 v 63.6 years; P < 0.01). A critical care discharge (CCD) or CCR
      preceded 39.5% and HTR only, 57.9% of events. A CCD preceded 25.7% of cardiac
      arrests, 32.4% of MET calls, and 29.0% unanticipated ICU admissions. Patients
      with a CCR or CCD had lower hospital mortality than those with an HTR only (27.3%
      v 41.7%; P < 0.01), and shorter median ICU length of stay (2 [interquartile
      range, 1-3] v 2 [interquartile range, 1-6] days; P = 0.04). CONCLUSIONS: Medical
      reviews in the 24 hours before an adverse event are common. The type of medical
      review may influence patient outcome and thus may be a useful measure of rapid
      response systems and critical care performance.

PMID- 21880006
TI  - Paracetamol therapy for septic critically ill patients: a retrospective
      observational study.
AB  - BACKGROUND: There is little information on the use of paracetamol for septic
      critically ill patients. We hypothesised that paracetamol use is common in such
      patients, but its administration is not predictably related to body temperature.
      OBJECTIVE: To study the epidemiology and associations of paracetamol use in a
      cohort of septic critically ill patients. DESIGN: Retrospective observational
      study. PATIENTS AND SETTING: Cohort of 106 patients admitted with a sepsis
      related diagnostic code to the intensive care unit of a tertiary hospital, 14
      December 2009 - 8 August 2010. METHODS: Using the ICU database, we identified all
      patients admitted with sepsis during the study period. We audited their
      electronic medical records to identify paracetamol administration and body
      temperature. The paracetamol administered and tympanic temperature at 00:00,
      06:00, 12:00 and 18:00 hours for the first 7 days of admission were recorded. The
      reason for paracetamol administration was not documented. RESULTS: 73/106 (69%)
      patients received paracetamol at least once; 10% of all patients and 23% of
      postoperative patients had paracetamol for every temperature measurement. The
      median length of stay was 3 days and the mean total ICU paracetamol dose per
      patient was 6.4 g. Overall, 44% of patients received paracetamol for their peak
      temperature (56% in the fever group v 37% in the non-fever group; P = 0.07). Only
      36/106 patients had a fever and 88% in the fever group had paracetamol at least
      once in the first 7 days, compared with 60% in the non-fever group (P=0.004).
      After adjustment for key variables, patients with fever were more likely to
      receive paracetamol (odds ratio, 6.8 [95% CI, 1.9- 24.7]; P=0.004). Patients with
      fever were more likely to die in ICU than patients without fever (P<0.001),
      although those who died in ICU did not receive more paracetamol. CONCLUSIONS:
      Paracetamol administration is common among septic critically ill patients with or
      without fever, and more likely to occur when fever is present. However,
      paracetamol is not predictably given for the highest temperature in febrile
      patients. Future investigations are needed to understand under what circumstances
      and why paracetamol is given or not given to febrile or afebrile septic ICU
      patients.

PMID- 21880007
TI  - Candida sake candidaemia in non-neutropenic critically ill patients: a case
      series.
AB  - Candida sake infections are rare, but have been shown to cause severe infections
      including fungal endocarditis, peritonitis and bloodstream infection. As the
      reported incidence of C. sake candidaemia is very low, there is a dearth of data
      regarding the associated risk factors, antifungal agent-susceptibility patterns,
      optimal treatment policies, clinical course and outcomes of patients with such
      infections. We report a series of seven non-neutropenic intensive care unit
      patients with C. sake candidaemia. Most of the patients were men (6/7), were over
      65 years of age (5/7) and had a history of recent hospitalisation (4/7) and
      comorbidities (4/7). However, all seven patients had a previous history of
      antibiotic uptake for more than 5 days and had a central venous catheter in situ
      at the time of taking specimens for culture. In four patients, infection was
      azole-resistant. Four patients required vasopressor support, three required
      mechanical ventilation and two required renal replacement therapy. Three of the
      seven patients died. This case series emphasises the importance of performing
      species identification and antifungal susceptibility testing in ICU patients with
      candidaemia, especially those with advanced age, underlying chronic diseases,
      indwelling vascular catheters, or a history of previous antibiotics or recent
      hospitalisations, as these patients may be at an increased risk of developing
      rare Candida infections like C. sake. Moreover, these rare Candida species may be
      more frequently resistant to azole antifungal agents, and may be associated with
      significant mortality.

PMID- 21880008
TI  - Cardiac arrest complicating neostigmine use for bowel opening in a critically ill
      patient.
AB  - Absence of bowel opening is common among critically ill patients. Neostigmine can
      be used to achieve stool passage after other treatments have been ineffective.
      Here, we report a case of cardiac arrest complicating neostigmine use in a 16
      year-old woman with cerebral palsy who was being treated in the intensive care
      unit after orthopaedic surgery. Bradycardia is a recognised complication of
      neostigmine administration; however, cardiac arrest has not been reported
      previously.

PMID- 21880009
TI  - A systematic review of the accuracy of peripheral thermometry in estimating core
      temperatures among febrile critically ill patients.
AB  - BACKGROUND: There is uncertainty about the accuracy of peripheral thermometers in
      measuring temperatures within the febrile physiological range. OBJECTIVE: To
      determine the accuracy of peripheral thermometers in detecting febrile core
      temperatures among critically ill patients, and, if required, to determine a
      standard conversion equation to improve accuracy. METHODS: A systematic search of
      MEDLINE, Embase, the Cochrane Central Register of Controlled Trials and PubMed
      was undertaken to identify clinical trials comparing peripheral thermometry in
      critically ill adult patients with core temperatures > 37.5 degrees C. Our
      prespecified plan was to perform a meta-analysis of the clinical accuracy of mean
      peripheral thermometer temperature difference from core temperature and
      calculation of limits of agreement. RESULTS: Systematic review identified three
      studies that compared infrared tympanic, rectal or oral thermometer readings with
      pulmonary artery catheter core temperature readings among critically ill adults
      with fever. Studies were heterogeneous and all failed to report appropriate
      measurements of variation for the estimates of clinical accuracy, which prevented
      meta-analysis and limited interpretation of the results. Mean differences were
      within +/- 0.2 degrees C in five of seven tympanic thermometer/mode/ temperature
      combinations and in the one oral thermometer studied. All of three rectal
      thermometer/temperature combinations studied reported mean differences outside
      this range. CONCLUSION: The identified studies suggest that in critically ill
      patients, tympanic and oral thermometry provide, on average, accurate measures of
      core temperatures within the febrile range and can be recommended for this
      purpose. Further studies with appropriate statistical methods are required to
      assess the accuracy of peripheral thermometers among critically ill patients with
      fever.

PMID- 21880010
TI  - Subclinical acute kidney injury: a novel biomarker-defined syndrome.

PMID- 21880011
TI  - Echocardiography training at the University of Queensland.

PMID- 21880012
TI  - Characterization of a novel peripheral pro-lipolytic mechanism in mice: role of
      VGF-derived peptide TLQP-21.
AB  - The peptides encoded by the VGF gene are gaining biomedical interest and are
      increasingly being scrutinized as biomarkers for human disease. An
      endocrine/neuromodulatory role for VGF peptides has been suggested but never
      demonstrated. Furthermore, no study has demonstrated so far the existence of a
      receptor-mediated mechanism for any VGF peptide. In the present study, we provide
      a comprehensive in vitro, ex vivo and in vivo identification of a novel pro
      lipolytic pathway mediated by the TLQP-21 peptide. We show for the first time
      that VGF-immunoreactivity is present within sympathetic fibres in the WAT (white
      adipose tissue) but not in the adipocytes. Furthermore, we identified a saturable
      receptor-binding activity for the TLQP-21 peptide. The maximum binding capacity
      for TLQP-21 was higher in the WAT as compared with other tissues, and selectively
      up-regulated in the adipose tissue of obese mice. TLQP-21 increases lipolysis in
      murine adipocytes via a mechanism encompassing the activation of
      noradrenaline/beta-adrenergic receptors pathways and dose-dependently decreases
      adipocytes diameters in two models of obesity. In conclusion, we demonstrated a
      novel and previously uncharacterized peripheral lipolytic pathway encompassing
      the VGF peptide TLQP-21. Targeting the sympathetic nerve-adipocytes interaction
      might prove to be a novel approach for the treatment of obesity-associated
      metabolic complications.

PMID- 21880013
TI  - Protein metabolism and gene expression in skeletal muscle of critically ill
      patients with sepsis.
AB  - Muscle wasting negatively affects morbidity and mortality in critically ill
      patients. This progressive wasting is accompanied by, in general, a normal muscle
      PS (protein synthesis) rate. In the present study, we investigated whether muscle
      protein degradation is increased in critically ill patients with sepsis and which
      proteolytic enzyme systems are involved in this degradation. Eight patients and
      seven healthy volunteers were studied. In vivo muscle protein kinetics was
      measured using arteriovenous balance techniques with stable isotope tracers. The
      activities of the major proteolytic enzyme systems were analysed in combination
      with mRNA expression of genes related to these proteolytic systems. Results show
      that critically ill patients with sepsis have a variable but normal muscle PS
      rate, whereas protein degradation rates are dramatically increased (up to 160%).
      Of the major proteolytic enzyme systems both the proteasome and the lysosomal
      systems had higher activities in the patients, whereas calpain and caspase
      activities were not changed. Gene expression of several genes related to the
      proteasome system was increased in the patients. mRNA levels of the two main
      lysosomal enzymes (cathepsin B and L) were not changed but, conversely, genes
      related to calpain and caspase had a higher expression in the muscles of the
      patients. In conclusion, the dramatic muscle wasting seen in critically ill
      patients with sepsis is due to increased protein degradation. This is facilitated
      by increased activities of both the proteasome and lysosomal proteolytic systems.

PMID- 21880014
TI  - Stemness characteristics and osteogenic potential of sheep amniotic epithelial
      cells.
AB  - We set out to characterize stemness properties and osteogenic potential of sheep
      AEC (amniotic epithelial cells). AEC were isolated from 3-month-old fetuses and
      expanded in vitro for 12 passages. The morphology, surface markers, stemness
      markers and osteogenic differentiation were inspected after 1, 6 and 12 passages
      of expansion, with an average doubling time of 24 h. AEC clearly expressed the
      stemness markers Oct-3/4 (octamer-binding protein-3/4), Nanog, Sox2 and TERT
      (telomerase reverse transcriptase) and displayed low levels of global DNA
      methylation. Culture had moderate effects on cell conditions; some adhesion
      molecules progressively disappeared from the cell surface, and the expression of
      Sox2 and TERT was slightly reduced while Nanog increased. No changes occurred in
      the levels of DNA methylation. Cells organized in 3D spheroids were used for IVD
      (in vitro differentiation). Within these structures the cells developed a complex
      intercellular organization that involved extensive intercellular coupling despite
      continuous cell migration. Marked deposition of calcein in the ECM (extracellular
      matrix), increased ALP (alkaline phosphatase) activity, expression of bone
      related genes (osteocalcin) and the matrix mineralization shown by Alizarin Red
      staining demonstrate that AEC can undergo rapid and extensive osteogenic
      differentiation. AEC introduced in experimental bone lesions survived in the site
      of implantation for 45 days and supported consistent bone neoformation, thus
      showing promising potential applications in osteogenic regenerative medicine.

PMID- 21880015
TI  - LRPPRC mutation suppresses cytochrome oxidase activity by altering mitochondrial
      RNA transcript stability in a mouse model.
AB  - LRPPRC (leucine-rich pentatricopeptide repeat-containing) has been shown to be
      essential for the maturation of COX (cytochrome c oxidase), possibly by
      stabilizing RNA transcripts of COXI, COXII and COXIII genes encoded in mtDNA
      (mitochondrial DNA). We established a mouse 'gene-trap' model using ES cells
      (embryonic stem cells) in which the C-terminus of LRPPRC has been replaced with a
      beta-geo construct. Mice homozygous for this modification were found to be
      subject to embryonic lethality, with death before 12.5 dpc (days post-coitum).
      Biochemical analysis of MEFs (mouse embryonic fibroblasts) isolated from
      homozygous mutants showed a major decrease in COX activity, with slight
      reductions in other respiratory chain complexes with mtDNA encoded components.
      Constructs of LRPPRC containing different numbers of PPRs (pentatricopeptide
      repeats) were expressed as recombinant proteins and tested for their ability to
      bind to the COXI mRNA transcript. Full binding required the first 19 PPR motifs.
      A specific segment of COXI mRNA was identified as the binding target for LRPPRC,
      encoded by mouse mtDNA nucleotides 5961-6020. These data strongly suggest that
      LRPPRC is involved in the maturation of COX, and is involved in stabilizing of
      mitochondrial mRNAs encoding COX transcripts.

PMID- 21880016
TI  - Aldehyde stress and up-regulation of Nrf2-mediated antioxidant systems accompany
      functional adaptations in cardiac mitochondria from mice fed n-3 polyunsaturated
      fatty acids.
AB  - Diets replete with n-3 PUFAs (polyunsaturated fatty acids) are known to have
      therapeutic potential for the heart, although a specifically defined duration of
      the n-3 PUFA diet required to achieve these effects remains unknown, as does
      their mechanism of action. The present study was undertaken to establish whether
      adaptations in mitochondrial function and stress tolerance in the heart is
      evident following short- (3 weeks) and long- (14 weeks) term dietary intervention
      of n-3 PUFAs, and to identify novel mechanisms by which these adaptations occur.
      Mitochondrial respiration [mO2 (mitochondrial O2)], H2O2 emission [mH2O2
      (mitochondrial H2O2)] and Ca2+-retention capacity [mCa2+ (mitochondrial Ca2+)]
      were assessed in mouse hearts following dietary intervention. Mice fed n-3 PUFAs
      for 14 weeks showed significantly lower mH2O2 and greater mCa2+ compared with all
      other groups. However, no significant differences were observed after 3 weeks of
      the n-3 PUFA diet, or in mice fed on an HFC (high-fat control) diet enriched with
      vegetable shortening, containing almost no n-3 PUFAs, for 14 weeks.
      Interestingly, expression and activity of key enzymes involved in antioxidant and
      phase II detoxification pathways, all mediated by Nrf2 (nuclear factor E2-related
      factor 2), were elevated in hearts from mice fed the n-3 PUFA diet, but not
      hearts from mice fed the HFC diet, even at 3 weeks. This increase in antioxidant
      systems in hearts from mice fed the n-3 PUFA diet was paralleled by increased
      levels of 4-hydroxyhexenal protein adducts, an aldehyde formed from peroxidation
      of n-3 PUFAs. The findings of the present study demonstrate distinct time
      dependent effects of n-3 PUFAs on mitochondrial function and antioxidant response
      systems in the heart. In addition, they are the first to provide direct evidence
      that non-enzymatic oxidation products of n-3 PUFAs may be driving mitochondrial
      and redox-mediated adaptations, thereby revealing a novel mechanism for n-3 PUFA
      action in the heart.

PMID- 21880017
TI  - Hypoxia and reoxygenation modulate the arrhythmogenic activity of the pulmonary
      vein and atrium.
AB  - Ischaemia and reperfusion contribute to the genesis of AF (atrial fibrillation).
      PVs (pulmonary veins) and the atria are important foci for AF initiation and
      maintenance. However, the effect of ischaemia and reperfusion on PVs and the
      atria has not yet been fully elucidated. In the present study, conventional
      microelectrodes were used to record the APs (action potentials) in isolated
      rabbit PV, LA (left atrium) and RA (right atrium) specimens during hypoxia and
      reoxygenation, and pharmacological interventions. Hypoxia reduced the PV beating
      rates from 1.8+/-0.1 to 1.3+/-0.2 and 0.8+/-0.1 Hz at 30 and 60 min respectively
      (n=8, P<0.005), and induced EAD (early after depolarization) in three (37.5%) of
      the PVs and DAD (delayed after depolarization) in one (12.5%) of the PVs.
      Reoxygenation increased the PV spontaneous rate to 1.4+/-0.2 Hz (P<0.05) and
      induced PV burst firings (3.5+/-0.1 Hz, P<0.001) in six (75%) of the PVs. Hypoxia
      shortened the AP duration in the LA and PVs, but not in the RA. Pretreatment with
      glibenclamide attenuated hypoxia-induced decreases in the PV spontaneous activity
      and the shortening of the LA and PV AP duration. Similar to those in hypoxia, the
      K(ATP) (ATP-sensitive potassium) channel opener pinacidil (30 MUM) decreased PV
      spontaneous activity and shortened the AP duration. Pretreatment with 5 mM N-MPG
      [N-(mercaptopropionyl)glycine; a hydroxyl (*OH) free-radical scavenger] or 300
      MUM chloramphenicol [a cytochrome P450 inhibitor that reduces ROS (reactive
      oxygen species)] attenuated the rate changes induced by hypoxia and
      reoxygenation, and also decreased the burst firing incidence. In conclusion,
      hypoxia and reoxygenation significantly increased PV arrhythmogenesis and induced
      different electrophysiological responses in the RA and LA, which may play a role
      in the pathophysiology of AF.

PMID- 21880019
TI  - Dissecting structure-function-stability relationships of a thermostable GH5-CBM3
      cellulase from Bacillus subtilis 168.
AB  - Cellulases participate in a number of biological events, such as plant cell wall
      remodelling, nematode parasitism and microbial carbon uptake. Their ability to
      depolymerize crystalline cellulose is of great biotechnological interest for
      environmentally compatible production of fuels from lignocellulosic biomass.
      However, industrial use of cellulases is somewhat limited by both their low
      catalytic efficiency and stability. In the present study, we conducted a detailed
      functional and structural characterization of the thermostable BsCel5A (Bacillus
      subtilis cellulase 5A), which consists of a GH5 (glycoside hydrolase 5) catalytic
      domain fused to a CBM3 (family 3 carbohydrate-binding module). NMR structural
      analysis revealed that the Bacillus CBM3 represents a new subfamily, which lacks
      the classical calcium-binding motif, and variations in NMR frequencies in the
      presence of cellopentaose showed the importance of polar residues in the
      carbohydrate interaction. Together with the catalytic domain, the CBM3 forms a
      large planar surface for cellulose recognition, which conducts the substrate in a
      proper conformation to the active site and increases enzymatic efficiency.
      Notably, the manganese ion was demonstrated to have a hyper-stabilizing effect on
      BsCel5A, and by using deletion constructs and X-ray crystallography we determined
      that this effect maps to a negatively charged motif located at the opposite face
      of the catalytic site.

PMID- 21880018
TI  - Reduction in BACE1 decreases body weight, protects against diet-induced obesity
      and enhances insulin sensitivity in mice.
AB  - Insulin resistance and impaired glucose homoeostasis are important indicators of
      Type 2 diabetes and are early risk factors of AD (Alzheimer's disease). An
      essential feature of AD pathology is the presence of BACE1 (beta-site amyloid
      precursor protein-cleaving enzyme 1), which regulates production of toxic amyloid
      peptides. However, whether BACE1 also plays a role in glucose homoeostasis is
      presently unknown. We have used transgenic mice to analyse the effects of loss of
      BACE1 on body weight, and lipid and glucose homoeostasis. BACE1-/- mice are lean,
      with decreased adiposity, higher energy expenditure, and improved glucose
      disposal and peripheral insulin sensitivity than wild-type littermates. BACE1-/-
      mice are also protected from diet-induced obesity. BACE1-deficient skeletal
      muscle and liver exhibit improved insulin sensitivity. In a skeletal muscle cell
      line, BACE1 inhibition increased glucose uptake and enhanced insulin sensitivity.
      The loss of BACE1 is associated with increased levels of UCP1 (uncoupling protein
      1) in BAT (brown adipose tissue) and UCP2 and UCP3 mRNA in skeletal muscle,
      indicative of increased uncoupled respiration and metabolic inefficiency. Thus
      BACE1 levels may play a critical role in glucose and lipid homoeostasis in
      conditions of chronic nutrient excess. Therefore strategies that ameliorate BACE1
      activity may be important novel approaches for the treatment of diabetes.

PMID- 21880020
TI  - Full-length sequence of a novel null allele HLA-A*23:38N identified in an
      individual from Guadeloupe.
AB  - The new HLA-A*23:38N allele shows a single-base deletion in exon 2, resulting in
      a frame shift and a premature stop codon.

PMID- 21880021
TI  - Incidence of cervical cancer and age-specific survival of small cell cervical
      carcinoma in Taiwan.
AB  - OBJECTIVE: To determine the incidence of cervical cancer and the age-specific
      survival from small cell cervical carcinoma in Taiwan. DESIGN: Retrospective
      study. Setting. Taiwan. POPULATION: Women diagnosed with cervical cancer from
      1991 to 2005. METHODS: Analysis of data from the National Cancer Registration
      System and National Death Certification System. MAIN OUTCOME MEASURES: Incidence
      and age at diagnosis of cervical carcinoma and age-specific and overall survival
      from small cell cervical carcinoma. RESULTS: During the study period, 36 122
      women were diagnosed with cervical cancer, and 81.8% had squamous cell carcinoma
      (SCC). For the periods 1991-1995, 1996-2000 and 2001-2005, the mean age at
      diagnosis increased from 53.9 +/- 13.3 to 55.0 +/- 14.9 and then to 56.7 +/- 14.7
      years, respectively. The incidence of SCC decreased from 1991 to 2005. During the
      same period, non-significant increases of adenocarcinoma and small cell carcinoma
      were noted. For SCC, occurrence peaked in 1991-1995 in patients 50-59 years of
      age. From 1996 to 2005, it peaked in patients 40-49 years of age. For cervical
      adenocarcinoma, occurrence peaked in patients 40-49 years of age, with a steady
      increase in this age group from 1991 to 2005. Occurrence of small cell cervical
      carcinoma peaked in the period 1991-1995 in patients 30-39 years of age. During
      the 15 years of the study, the overall mortality rate of the 198 patients with
      small cell cervical carcinoma was 65.7%. CONCLUSIONS: In Taiwan, the incidence of
      small cell cervical carcinoma and adenocarcinoma tended to increase, but the
      incidence of squamous cell cervical carcinoma significantly decreased during the
      period 1991-2005.

PMID- 21880022
TI  - Acute digital ischemia complicating gemcitabine and carboplatin combination
      chemotherapy for ovarian cancer.

PMID- 21880023
TI  - Does exercise during pregnancy prevent postnatal depression? A randomized
      controlled trial.
AB  - OBJECTIVE: To study whether exercise during pregnancy reduces the risk of
      postnatal depression.  DESIGN:  Randomized controlled trial.  SETTING:  Trondheim
      and Stavanger University Hospitals, Norway.  POPULATION AND SAMPLE:  Eight
      hundred and fifty-five pregnant women were randomized to intervention or control
      groups.  METHODS:  The intervention was a 12 week exercise program, including
      aerobic and strengthening exercises, conducted between week 20 and 36 of
      pregnancy. One weekly group session was led by physiotherapists, and home
      exercises were encouraged twice a week. Control women received regular antenatal
      care.  MAIN OUTCOME MEASURES:  Edinburgh Postnatal Depression Scale (EPDS)
      completed three months after birth. Scores of 10 or more and 13 or more suggested
      probable minor and major depression, respectively.  RESULTS:  Fourteen of 379
      (3.7%) women in the intervention group and 17 of 340 (5.0%) in the control group
      had an EPDS score of >=10 (p=0.46), and four of 379 (1.2%) women in the
      intervention group and eight of 340 (2.4%) in the control group had an EPDS score
      of >=13 (p=0.25). Among women who did not exercise prior to pregnancy, two of 100
      (2.0%) women in the intervention group and nine of 95 (9.5%) in the control group
      had an EPDS score of >=10 (p=0.03).  CONCLUSIONS:  We did not find a lower
      prevalence of high EPDS scores among women randomized to regular exercise during
      pregnancy compared with the control group. However, a subgroup of women in the
      intervention group who did not exercise regularly prior to pregnancy had a
      reduced risk of postnatal depression.

PMID- 21880024
TI  - Labor progress among women attempting a trial of labor after cesarean. Do they
      have their own rules?
AB  - OBJECTIVE: To examine the pattern of labor progression among second parous women
      who had a vaginal birth after a cesarean (VBAC) compared with primiparous and
      multiparous women who delivered vaginally. DESIGN: Case-control study. SETTING:
      University hospital in Israel, August 2005 through November 2008. POPULATION: The
      cases were all 137 second parous women who had a VBAC during the study period.
      The control groups were: (1) 136 primiparous women; and (2) 137 women who had a
      second repeated vaginal delivery. METHODS: Data were extracted from the
      electronic medical records at admission, labor charts and medical records at
      discharge. Controls were frequency-matched to the study group for maternal age,
      gestational age and the work shift during which the delivery occurred. MAIN
      OUTCOME MEASURES: Length of the active phase of labor. Secondary outcomes were
      length of the second stage and incidence of vacuum extraction deliveries.
      Results. The length of the active phase was 176 +/- 116, 207 +/- 121 and 110 +/-
      66 minutes in the study, first and second control groups, respectively. The
      active phase and stage 2 of the study group were significantly shorter than in
      the first control group (p=0.02 and p=0.007, respectively) and longer than in the
      second control group (p=0.001 in both stages). The incidence of vacuum deliveries
      was higher (p=0.001) in the study group (13.9%) compared with the second control
      group (1.5%). CONCLUSIONS: The results suggest that the pattern of labor
      progression among second parous women undergoing a trial of labor after cesarean
      differs from second parous women undergoing a repeated vaginal delivery.
      Recognizing this dissimilarity may help in avoiding unnecessary, occasionally
      deleterious, interventions.

PMID- 21880025
TI  - Intimate partner violence and its association with pregnancy loss and pregnancy
      planning.
AB  - OBJECTIVE: To examine the effect of physical partner violence on pregnancy loss
      and unplanned pregnancy.  DESIGN: Cross-sectional, self-reported questionnaire
      survey. SETTING: A maternity ward of a university hospital in Munich, Germany. 
      SAMPLE: Women who gave birth within the previous seven days.  METHODS: The
      effects of physical partner violence on pregnancy loss and unplanned pregnancy
      were estimated using descriptive statistics based on chi(2) tests, bivariate
      logistic regression and multivariate logistic regression.  MAIN OUTCOME MEASURES:
      Physical partner violence was assessed using the Abuse Assessment Screen,
      information on pregnancy loss was derived from women's medical files and the
      assessment of pregnancy planning was based on women's self-reports.  RESULTS: The
      survey had a response rate of 73%; 29% of the women experienced pregnancy loss,
      13% reported that their last pregnancy was unplanned and 4% revealed physical
      violence by a current or previous partner. Physical partner violence was
      significantly associated with pregnancy loss (odds ratio 8.33, 95% confidence
      interval 2.01-34.59) and unplanned last pregnancy (odds ratio 5.03, 95%
      confidence interval 1.21-21.26), even after adjusting for other commonly known
      explanatory factors, such as number of children, women's age and women's and
      their partners' education level and employment, marital status, financial
      situation and support during pregnancy.  CONCLUSIONS: Physical partner violence
      is an important factor in understanding pregnancy loss and unplanned pregnancy.
      Inquiring about the existence of intimate partner violence among these women
      might help to identify women in need of domestic violence services.

PMID- 21880026
TI  - Hepatocellular carcinoma and vitamin D: a review.
AB  - The non-classical actions of vitamin D, namely antiproliferation, pro
      differentiation, pro-apoptosis, anti-inflammation, and immune regulation, have
      received great attention during the past decade. Increasing evidence from
      epidemiological studies showing the inverse association between vitamin D status
      and incidence of many forms of cancer as well as biochemical studies has
      suggested that vitamin D deficiency may play a role in the cause and progression
      of these types of cancer. Recently, vitamin D and its analogs have been deemed as
      potential regimen to treat a variety of cancers alone or in combination with
      other drugs. Although, the epidemiologic evidence regarding the association of
      vitamin D and hepatocellular carcinoma (HCC) is still inconclusive, biochemical
      evidence clearly indicates that HCC cells are responsive to the inhibitory effect
      of vitamin D and its analogs. In this review, we discuss the current status of
      HCC and its treatment, the source, metabolism, functions, and the mechanism of
      actions of vitamin D, and the biochemical studies of vitamin D analogs and their
      implications in the prevention and treatment of HCC.

PMID- 21880027
TI  - An Al-inducible MATE gene is involved in external detoxification of Al in rice.
AB  - A number of plant species, including rice, secretes citrate from roots in
      response to Al stress. Here we characterized the functions of a gene, OsFRDL4
      (Os01g0919100) that belongs to the multidrug and toxic compound extrusion (MATE)
      family in rice (Oryza sativa). Heterologous expression in Xenopus oocyte showed
      that the OsFRDL4 protein was able to transport citrate and was activated by Al.
      The expression level of the OsFRDL4 gene in roots was very low in the absence of
      Al, but was greatly enhanced by Al after short exposure. Furthermore, the OsFRDL4
      expression was regulated by ART1, a C2H2-type zinc finger transcription factor
      for Al tolerance. Transient expression of OsFRDL4 in onion epidermal cells showed
      that it localized to the plasma membrane. Immunostaining showed that OsFRDL4 was
      localized in all cells in the root tip. These expression patterns and cell
      specificity of localization of OsFRDL4 are different from other MATE members
      identified previously. Knockout of OsFRDL4 resulted in decreased Al tolerance and
      decreased citrate secretion compared with the wild-type rice, but did not affect
      citrate concentration in the xylem sap. Furthermore, there is a positive
      correlation between OsFRDL4 expression level and the amount of citrate secretion
      in rice cultivars that are differing in Al tolerance. Taken together, our results
      show that OsFRDL4 is an Al-induced citrate transporter localized at the plasma
      membrane of rice root cells and is one of the components of high Al tolerance in
      rice.

PMID- 21880028
TI  - Early assessment of visual acuity after cataract surgery in rural Indonesia.
AB  - BACKGROUND: The accuracy and impact on service uptake of early examination after
      cataract surgery is not known. DESIGN:   Prospective cohort study. PARTICIPANTS:
      Cataract patients in rural Indonesia. METHODS: Visual acuity was measured
      preoperatively, 1day, 1-3, 4-6 and >12weeks after surgery, and 6-8months
      postoperatively at an outreach examination. Acceptance of second-eye surgery and
      spectacles was evaluated. MAIN OUTCOME MEASURE: Presenting visual acuity in the
      operated eye. RESULTS: Among 241 subjects (extracapsular surgery 84%),
      examinations at 1day, 1-3, 4-6 and >12weeks and 6-8months were completed for 100%
      (241), 90.9% (219), 67.6% (163), 22.0% (53) and 80.0% (193), respectively. Among
      subjects at the final examination (mean age 65.8+/-10.6years, 51.8% male), 73.6%
      had bilateral preoperative presenting visual acuity<=6/60. By 4-6weeks, the
      proportion with good (>=6/18) or poor (<=6/60) visual acuity did not differ
      significantly from the final examination. Among 49 persons accepting free second
      eye surgery, 69.4% (34) and 16.3% (8) returned to clinic at 4-6 and >12weeks,
      respectively. Among 131 patients (67.9%) paying US$7 for glasses, 94 (71.8%) and
      30 (22.9%) attended 4- to 6- and >12-week examinations, respectively. CONCLUSION:
      Even with large-incision surgery, early assessment of postoperative vision is
      representative of final vision, and may help deliver postoperative services to
      more of those needing them.

PMID- 21880029
TI  - Use of an antispasmodic (rociverine) to shorten the length of labor: a
      randomized, placebo-controlled trial.
AB  - OBJECTIVE: To determine the effectiveness of rociverine, an antispasmodic drug,
      for reducing the duration of labor among nulliparous women managed according to a
      standard intrapartum protocol. DESIGN: Randomized controlled trial. SETTING: An
      academic tertiary care hospital. POPULATION: Nulliparae in spontaneous active
      labor, with cervical dilatation between 3 and 5 cm. METHODS: Participants were
      randomly assigned to receive either an intramuscular injection of 20mg rociverine
      (n=55) or the same volume of saline (n=56). MAIN OUTCOME MEASURE: Cervical
      dilatation rate (from administration of study drug to full dilatation). RESULTS:
      Laboring women who received rociverine had faster cervical dilatation than those
      assigned to placebo (2.43 +/- 1.84 vs. 1.85 +/- 1.38 cm/hour, p=0.03). The time
      interval from treatment administration to full cervical dilatation was shorter in
      the rociverine group than in the placebo group (220 +/- 125 vs. 278 +/- 129 min,
      p=0.04). No difference was found in any other obstetric outcome. No adverse
      effects have been recorded from rociverine administration. CONCLUSIONS:
      Intrapartum administration of rociverine to nulliparous women may help to reduce
      the duration of the first stage of labor in a context of uniform labor
      management.

PMID- 21880030
TI  - The relation of psychological distress to salivary and serum cortisol levels in
      pregnant women shortly after the diagnosis of a structural fetal anomaly.
AB  - OBJECTIVE:  To examine the association between psychological distress and levels
      of salivary cortisol (SalC) and the ratio of serum cortisol to cortisol-binding
      globulin (SC/CBG) in pregnant women shortly after the diagnosis of a structural
      fetal anomaly. DESIGN. A prospective, observational study.  SETTING:  Tertiary
      referral center for fetal medicine.  POPULATION:  Pregnant women with (study
      group, n=126) and without a fetal structural anomaly (comparison group, n=106)
      were included. Gestational age (GA) was >12weeks.  METHODS:  Psychological
      distress was assessed by Impact of Event Scale (IES-22), General Health
      Questionnaire (GHQ-28) and Edinburgh Postnatal Depression Scale (EPDS). Salivary
      cortisol was measured in the evening and SC/CBG in the morning. MAIN OUTCOME
      MEASURES. Levels of SalC (in nanomoles per liter) and SC/CBG.  RESULTS:  Median
      (range) GA at assessment was 19 (12-38) and 19 (13-22)weeks in the study and the
      comparison group, respectively. The study group had significantly higher
      psychological distress levels (p<=0.001) than the comparison group in all outcome
      measures. Salivary cortisol correlated with GA in both groups (p<0.004). In
      subanalyses including only women with GA 18-22 weeks, and excluding smokers or
      women with chronic diseases or medication which might interfere with cortisol
      levels, there were no relations of SalC or SC/CBG with the psychometric variables
      in the study group. CONCLUSIONS. Women with detected fetal malformation had high
      psychological distress scores. The lack of association between psychological
      distress and SalC or SC/CBG suggests a blunted response of the hypothalamic
      pituitary-adrenal axis following recent psychological stress activation in the
      second trimester of pregnancy.

PMID- 21880031
TI  - The air-Q((r)) intubating laryngeal airway vs the LMA-ProSeal(TM) : a
      prospective, randomised trial of airway seal pressure.
AB  - We performed a prospective, open-label, randomised controlled trial comparing the
      air-Q((r)) against the LMA-ProSealTM in adults undergoing general anaesthesia.
      One hundred subjects (American Society of Anesthesiologists physical status 1-3)
      presenting for elective, outpatient surgery were randomly assigned to 52 air
      Q((r)) and 48 ProSeal devices. The primary study endpoint was airway seal
      pressure. Oropharyngolaryngeal morbidity was assessed secondarily. Mean (SD)
      airway seal pressures for the air-Q((r)) and ProSeal were 30 (7) cmH (2) O and 30
      (6) cmH(2) O, respectively (p = 0.47). Postoperative sore throat was more common
      with the air-Q((r)) (46% vs 38%, p = 0.03) as was pain on swallowing (30% vs 5%,
      p = 0.01). In conclusion, the air-Q((r)) performs well as a primary airway during
      the maintenance of general anaesthesia with an airway seal pressure similar to
      that of the ProSeal, but with a higher incidence of postoperative
      oropharyngolaryngeal complaints.

PMID- 21880032
TI  - Voriconazole versus itraconazole for antifungal prophylaxis following allogeneic
      haematopoietic stem-cell transplantation.
AB  - Antifungal prophylaxis for allogeneic haematopoietic stem-cell transplant
      (alloHCT) recipients should prevent invasive mould and yeast infections (IFIs)
      and be well tolerated. This prospective, randomized, open-label, multicentre
      study compared the efficacy and safety of voriconazole (234 patients) versus
      itraconazole (255 patients) in alloHCT recipients. The primary composite
      endpoint, success of prophylaxis, incorporated ability to tolerate study drug for
      >= 100 d (with <= 14 d interruption) with survival to day 180 without
      proven/probable IFI. Success of prophylaxis was significantly higher with
      voriconazole than itraconazole (48.7% vs. 33.2%, P < 0.01); more voriconazole
      patients tolerated prophylaxis for 100 d (53.6% vs. 39.0%, P < 0.01; median total
      duration 96 vs. 68 d). The most common (>10%) treatment-related adverse events
      were vomiting (16.6%), nausea (15.8%) and diarrhoea (10.4%) for itraconazole, and
      hepatotoxicity/liver function abnormality (12.9%) for voriconazole. More
      itraconazole patients received other systemic antifungals (41.9% vs. 29.9%, P <
      0.01). There was no difference in incidence of proven/probable IFI (1.3% vs.
      2.1%) or survival to day 180 (81.9% vs. 80.9%) for voriconazole and itraconazole
      respectively. Voriconazole was superior to itraconazole as antifungal prophylaxis
      after alloHCT, based on differences in the primary composite endpoint.
      Voriconazole could be given for significantly longer durations, with less need
      for other systemic antifungals.

PMID- 21880033
TI  - 5-HT receptors as novel targets for optimizing pigmentary responses in dorsal
      skin melanophores of frog, Hoplobatrachus tigerinus.
AB  - BACKGROUND AND PURPOSE: Biochemical identification of 5-HT has revealed similar
      projection patterns across vertebrates. In CNS, 5-HT regulates major
      physiological functions but its peripheral functions are still emerging. The
      pharmacology of 5-HT is mediated by a diverse range of receptors that trigger
      different responses. Interestingly, 5-HT receptors have been detected in pigment
      cells indicating their role in skin pigmentation. Hence, we investigated the role
      of this monoaminergic system in amphibian pigment cells, melanophores, to further
      our understanding of its role in pigmentation biology together with its
      evolutionary significance. EXPERIMENTAL APPROACH: Pharmacological profiling of 5
      HT receptors was achieved using potent/selective agonists and antagonists. In
      vitro responses of melanophores were examined by Mean Melanophores Size Index
      assay. The melanophores of lower vertebrates are highly sensitive to external
      stimuli. The immediate cellular responses to drugs were defined in terms of
      pigment translocation within the cells. KEY RESULTS: 5-HT exerted strong
      concentration-dependent pigment dispersion at threshold dose of 1 * 10(-6) g.mL(
      1). Specific 5-HT(1) and 5-HT(2) receptor agonists, sumatriptan and myristicin.
      also induced dose-dependent dispersion. Yohimbine and metergoline synergistically
      antagonized sumatriptan-mediated dispersion, whereas trazodone partially blocked
      myristicin-induced dispersion. Conversely, 5-HT(3) and 5-HT(4) receptor agonists,
      1 (3 chlorophenyl) biguanide (1,3 CPB) and 5-methoxytryptamine (5-MT), caused a
      dose-dependent pigment aggregation. The aggregatory effect of 1,3 CPB was
      completely blocked by ondansetron, whereas L-lysine partially blocked the effect
      of 5-MT. CONCLUSIONS AND IMPLICATIONS: The results suggest that 5-HT-induced
      physiological effects are mediated via distinct classes of receptors, which
      possibly participate in the modulation of pigmentary responses in amphibian.

PMID- 21880035
TI  - A novel fluorescent histamine H(1)  receptor antagonist demonstrates the
      advantage of using fluorescence correlation spectroscopy to study the binding of
      lipophilic ligands.
AB  - BACKGROUND AND PURPOSE: Fluorescent ligands facilitate the study of ligand
      receptor interactions at the level of single cells and individual receptors.
      Here, we describe a novel fluorescent histamine H(1) receptor antagonist
      (mepyramine-BODIPY630-650) and use it to monitor the membrane diffusion of the
      histamine H(1) receptor. EXPERIMENTAL APPROACH: The human histamine H(1) receptor
      fused to yellow fluorescent protein (YFP) was transiently expressed in CHO-K1
      cells. The time course of binding of mepyramine-BODIPY630-650 to the H(1)
      receptor was determined by confocal microscopy. Additionally, fluorescence
      correlation spectroscopy (FCS) was used to characterize the diffusion coefficient
      of the H(1) receptor in cell membranes both directly (YFP fluorescence) and in
      its antagonist-bound state (with mepyramine-BODIPY630-650). KEY RESULTS:
      Mepyramine-BODIPY630-650 was a high-affinity antagonist at the histamine H(1)
      receptor. Specific membrane binding, in addition to significant intracellular
      uptake of the fluorescent ligand, was detected by confocal microscopy. However,
      FCS was able to quantify the receptor-specific binding in the membrane, as well
      as the diffusion coefficient of the antagonist-H(1) receptor-YFP complexes, which
      was significantly slower than when determined directly using YFP. FCS also
      detected specific binding of mepyramine-BODIPY630-650 to the endogenous H(1)
      receptor in HeLa cells. CONCLUSIONS AND IMPLICATIONS: Mepyramine-BODIPY630-650 is
      a useful tool for localizing the H(1) receptor using confocal microscopy.
      However, its use in conjunction with FCS allows quantification of ligand binding
      at the membrane, as well as determining receptor diffusion in the absence of
      significant bleaching effects. Finally, these methods can be successfully
      extended to endogenously expressed untagged receptors in HeLa cells.

PMID- 21880034
TI  - Clozapine, but not haloperidol, enhances glial D-serine and L-glutamate release
      in rat frontal cortex and primary cultured astrocytes.
AB  - BACKGROUND AND PURPOSE: Deficient transmission at the glutamate NMDA receptor is
      considered a key component of the pathophysiology of schizophrenia. However, the
      effects of antipsychotic drugs on the release of the endogenous NMDA receptor
      partial agonist, D-serine, remain to be clarified. EXPERIMENTAL APPROACH: We
      determined the interaction between antipsychotic drugs (clozapine and
      haloperidol) and transmission-modulating toxins (tetanus toxin, fluorocitrate,
      tetrodotoxin) on the release of L-glutamate and D-serine in the medial prefrontal
      cortex (mPFC) of freely moving rats, using microdialysis, and primary cultures of
      astrocytes using extreme high-pressure liquid chromatography. KEY RESULTS:
      Release of L-glutamate and D-serine in the mPFC and in cultured astrocytes was
      inhibited by tetanus toxin (a synaptobrevin inhibitor) and fluorocitrate (a glial
      toxin), whereas tetrodotoxin (a voltage-sensitive Na(+) blocker) inhibited
      depolarization-induced L-glutamate release in the mPFC without affecting that of
      D-serine. Clozapine (1 and 5 mg.kg(-1)), but not haloperidol (0.5 and 1 mg.kg(
      1)), dose-dependently increased L-glutamate and D-serine release from both
      astrocytes and mPFC. Clozapine-induced release of L-glutamate and D-serine was
      also reduced by tetanus toxin and fluorocitrate. Tetrodotoxin reduced clozapine
      induced mPFC L-glutamate release but not that of D-serine. Clozapine-induced L
      glutamate release preceded clozapine-induced D-serine release. MK-801 (a NMDA
      receptor antagonist) inhibited the delayed clozapine-induced L-glutamate release
      without affecting that of D-serine. CONCLUSIONS AND IMPLICATIONS: Clozapine
      predominantly activated glial exocytosis of D-serine, and this clozapine-induced
      D-serine release subsequently enhances neuronal L-glutamate release via NMDA
      receptor activation. The enhanced D-serine associated glial transmission seems a
      novel mechanism of action of clozapine but not haloperidol.

PMID- 21880036
TI  - Pharmacokinetics and in vivo potency of soluble epoxide hydrolase inhibitors in
      cynomolgus monkeys.
AB  - BACKGROUND AND PURPOSE: Soluble epoxide hydrolase inhibitors (sEHIs) possess anti
      inflammatory, antiatherosclerotic, antihypertensive and analgesic properties. The
      pharmacokinetics (PK) and pharmacodynamics in terms of inhibitory potency of
      sEHIs were assessed in non-human primates (NHPs). Development of a sEHI for use
      in NHPs will facilitate investigations on the role of sEH in numerous chronic
      inflammatory conditions. EXPERIMENTAL APPROACH: PK parameters of 11 sEHIs in
      cynomolgus monkeys were determined after oral dosing with 0.3 mg.kg(-1). Their
      physical properties and inhibitory potency in hepatic cytosol of cynomolgus
      monkeys were examined. Dose-dependent effects of the two inhibitors 1
      trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) and the related
      acetyl piperidine derivative, 1-trifluoromethoxyphenyl-3-(1-acetylpiperidin-4-yl)
      urea (TPAU), on natural blood eicosanoids, were determined. KEY RESULTS: Among
      the inhibitors tested, TPPU and two 4-(cyclohexyloxy) benzoic acid urea sEHIs
      displayed high plasma concentrations (>10 * IC(50)), when dosed orally at 0.3
      mg.kg(-1). Although the 4-(cyclohexyloxy) benzoic acid ureas were more potent
      against monkey sEH than piperidyl ureas (TPAU and TPPU), the latter compounds
      showed higher plasma concentrations and more drug-like properties. The C(max)
      increased with dose from 0.3 to 3 mg.kg(-1) for TPPU and from 0.1 to 3 mg.kg(-1)
      for TPAU, although it was not linear over this range of doses. As an indication
      of target engagement, ratios of linoleate epoxides to diols increased with TPPU
      administration. CONCLUSION AND IMPLICATIONS: Our data indicate that TPPU is
      suitable for investigating sEH biology and the role of epoxide-containing lipids
      in modulating inflammatory diseases in NHPs.

PMID- 21880037
TI  - Short-term infusion of a fish oil-based lipid emulsion modulates fatty acid
      status, but not immune function or (anti)oxidant balance: a randomized cross-over
      study.
AB  - BACKGROUND AND AIMS: Studies suggest clinical benefits of parenteral fish oil
      (FO), rich in n-3 polyunsaturated fatty acids (PUFAs), over soyabean oil (SO),
      rich in n-6 PUFAs, in patients with pro-inflammatory conditions such as sepsis
      and trauma. Because the mechanisms behind these observations remain unclear, the
      present study explored the effects of intravenous infusion of FO and SO on fatty
      acid incorporation, immune functions and (anti)oxidant balance in healthy human
      volunteers. METHODS: Saline, a SO emulsion and a FO emulsion were administered
      for one hour on three consecutive days at a rate of 0.2 g/kg BW/h to eight
      subjects in a randomized cross-over design with a 3-week interval between
      treatments. Plasma phospholipid and peripheral blood mononuclear cell (PBMC)
      fatty acid compositions, and leucocyte counts and functions were assessed prior
      to the first infusion (T = 0, baseline) and 1 day (T = 4, early effects) and 8
      days (T = 11, late effects) after the third infusion. RESULTS: Fish oil infusion
      significantly increased n-3 PUFA proportions and decreased n-6 PUFA proportions
      in plasma phospholipids and PBMCs. There were no differences in immune functions
      or (anti)oxidant balance between treatments at any time. CONCLUSIONS: The present
      lipid infusion protocol appears to be safe and well tolerated and provides
      significant incorporation of n-3 PUFAs into plasma phospholipids and PBMCs. In
      the absence of overt inflammation, no direct effects of FO were observed on
      immune function or (anti)oxidant balance. This model may be useful to evaluate
      effects of parenteral lipids in other settings, for example in individuals
      displaying an inflammatory state.

PMID- 21880038
TI  - Elevated E-selectin and diastolic blood pressure in diabetic children.
AB  - BACKGROUND: Cardiovascular risk markers are related to micro-angiopathy in
      children with type 1 diabetes (T1DM), but there is no information about their
      relationship with blood pressure (BP) and endothelial function. MATERIALS AND
      METHODS: This was a case-control study including 29 children with T1DM (mean age
      10.5 +/- 2.7 years, disease duration: 3.8 +/- 2.2 years) and 39 healthy controls
      (mean age: 9.8 +/- 2.7 years). We assessed 24-h ambulatory BP, vascular function
      and serum level of lipids, vascular cell adhesion molecule-1 (VCAM-1; ICAM) and
      selectins (E-selectin; P-selectin). RESULTS: The subject groups had similar
      physical characteristics and lipids level, except body mass index (BMI) which was
      higher in T1DM than in healthy children (18.6 +/- 2.6 vs. 16.7 +/- 2.5 kg/m(2), P
      = 0.003). Children with T1DM had increased 24 h diastolic BP z-score (0.62 +/-
      0.9 vs. -0.65 +/- 0.8, P < 0.001), even after adjustment for BMI, as well as
      higher VCAM-1 concentration (492 +/- 346 vs. 340 +/- 225 ng/mL, P = 0.039)
      compared to healthy subjects. Diastolic BP z-scores were associated with disease
      duration, E-selectin and triglyceride levels in the T1DM group (P < 0.05). E
      selectin was also related to triglycerides, otherwise there were no relationships
      between vascular function, markers and BP. CONCLUSION: E-selectin, an early
      atherosclerosis biomarker, is positively associated with diastolic BP values in
      children with T1DM, despite relatively short disease duration.

PMID- 21880039
TI  - Claims for improved survival from systemic corticosteroids in diverse conditions:
      an umbrella review.
AB  - BACKGROUND: Systemic corticosteroids have been proposed for numerous indications
      and there are many claims that corticosteroids can reduce mortality in diverse
      conditions. METHODS: We performed an umbrella, agenda-wide review of the evidence
      on systemic corticosteroids and mortality, focusing primarily on large trials
      (defined as those with > 100 deaths) and meta-analyses. Searches were performed
      in PubMed and Cochrane Central Register of Controlled Trials (last update
      February 2011). We also examined whether spurious subset analyses may be
      responsible for claims of survival benefits in indications where only small
      trials had been available. RESULTS: Among 257 identified randomized trials with
      mortality data in their abstract, we found 14 large trials pertaining to 10
      different indications. Although 10 of these 14 trials have reported statistically
      significant survival differences in subset analyses, none shows a nominally
      statistically significant (P < 0.05) decrease in death risk for any of the tested
      conditions when all deaths on all randomized patients are analysed. Meta-analyses
      for these conditions show statistically significant reductions in mortality only
      with antenatal corticosteroids for preterm labour (relative risk 0.77, 95% CI,
      0.67-0.89) and in tuberculous meningitis (relative risk 0.78, 95% CI, 0.67-0.91).
      For conditions without any large trials, statistically significant reductions in
      mortality in meta-analyses were noted for Pneumocystis pneumonia (relative risk
      0.54, 95% CI, 0.38-0.79) and alcoholic hepatitis (relative risk 0.63, 95% CI,
      0.50-0.80). Many small trials that claim significant benefits, even those for
      classic indications such as typhoid fever and tetanus, have shown these benefits
      only in subset analyses. CONCLUSIONS: Corticosteroids have been documented to
      decrease mortality in some indications, in particular, antenatal use for preterm
      labour, tuberculous meningitis, Pneumocystis pneumonia, and alcoholic hepatitis.
      Many postulated benefits of corticosteroids on mortality may reflect 'vibration
      of treatment effects' leading to false-positive claims from spurious subset
      analyses and even for standard indications, such biases may have inflated the
      treatment effect estimates. More large trials are needed for serious, common
      conditions where use of corticosteroids is proposed.

PMID- 21880040
TI  - Topo IIalpha gene alterations correlated with survival in patients with diffuse
      large B-cell lymphoma.
AB  - BACKGROUND: Topoisomerase IIalpha (topo IIalpha) protein expression has
      prognostic significance in many cancers. However, it is still unclear whether
      topo IIalpha protein expression and gene alterations play roles as prognostic
      factors in diffuse large B-cell lymphoma (DLBCL). MATERIALS AND METHODS: We
      selected 102 patients with DLBCL who were homogeneously treated with CHOP
      chemotherapy and followed up. Using tissue microarray technology, all of the
      cases, consisting of 25 germinal centre B-cell-like (GCB) and 77 nongerminal
      centre B-cell-like (non-GCB) types, were studied. Topo IIalpha protein expression
      was detected by immunohistochemistry. Gene copy number of topo IIalpha was
      analysed by chromogenic in situ hybridization. Cox regression, chi-square test
      and Kaplan-Meier statistics were performed using SPSS 15.0. RESULTS: Topo IIalpha
      protein overexpression was found in 91 (91/102, 89.2%) cases, while topo IIalpha
      gene amplification was absent in all cases. Chromosome 17 deletion was identified
      in 3 (3/102, 2.9%) cases, diploid in 66 (66/102, 64.7%) cases and aneuploidy in
      33 (33/102, 32.4%) cases. By multivariate analysis, no significant differences in
      progression-free survival (PFS) and overall survival (OS) were observed in
      patients with topo IIalpha protein overexpression (P > 0.05), while chromosome 17
      aneuploidy predicted worse PFS and OS (P < 0.001). CONCLUSIONS: These results
      suggested that chromosome 17 aneuploidy, but not topo IIalpha protein expression,
      could predict worse survival in patients with DLBCL.

PMID- 21880041
TI  - Evaluation of the automated collection and extended storage of apheresis
      platelets in additive solution.
AB  - BACKGROUND: Collecting apheresis platelets (PLTs) into additive solution has many
      potential benefits. The new Trima software (Version 6.0, CaridianBCT) allows
      automated addition of PLT additive solution (PAS) after collection, compared to
      Trima Version 5.1, which only collects PLTs into plasma. The aim of this study
      was to compare PLT quality during extended storage, after collection with the
      different Trima systems. STUDY DESIGN AND METHODS: Apheresis PLTs were collected
      using both Trima Accel apheresis systems. The test PLT units (n = 12) were
      collected using the new Trima Version 6.0 into PLT AS (PAS-IIIM), while the
      control units (n = 8) were collected into autologous plasma using Trima Version
      5.1. All units were stored for 9 days, and in vitro cell quality variables were
      evaluated during this time. RESULTS: PLTs collected in PAS-IIIM maintained a
      stable pH between 7.2 and 7.4, whereas plasma-stored apheresis units exhibited
      significantly increased acidity during storage, due to lactate accumulation and
      bicarbonate exhaustion. Plasma-stored PLTs also demonstrated a more rapid
      consumption of glucose. However, there was little difference in PLT activation or
      cytokine secretion between PAS-IIIM and control PLTs. CONCLUSION: These data
      indicate that apheresis PLT concentrates collected in PAS-IIIM, using Trima
      Version 6.0 software, maintained acceptable PLT metabolic and cellular
      characteristics until Day 9 of storage.

PMID- 21880042
TI  - Allogeneic single-donor cryoseal produced from fresh-frozen quarantine apheresis
      plasma as alternative for multidonor or autologous fibrin sealants.
AB  - BACKGROUND: Fibrin sealant is a human blood product consisting of two components:
      cryoprecipitate and thrombin. Commercial fibrin sealants are produced from
      multidonors, increasing the viral risk, and contain fibrinolytic inhibitors such
      as tranexamic acid or bovine aprotinin. Autologous fibrin sealants reduce the
      viral risk and are mostly produced during a surgical procedure or well in
      advance. Alternatively, the allogeneic single-donor fibrin sealant cryoseal can
      be used. In this study cryoseal was characterized and the manufacturing
      consistency of the production process was investigated. STUDY DESIGN AND METHODS:
      Cryoseal was produced from plasma collected on apheresis machines using a
      commercial device. In a research setting the protein composition and recovery
      were determined. Also, the manufacturing consistency of the production process
      was tested in a research setting as well as in a routine setting. RESULTS: In the
      research setting all produced cryoseal met the quality control requirements of a
      clotting time of less than 10 seconds and the presence of Factor (F)XIII
      (qualitative). In the routine setting, one procedure per year did not meet these
      requirements. The protein composition showed the following mean +/- standard
      deviation (%recovery) results: thrombin 25.7 +/- 11.1 IU/mL, fibrinogen 19.9 +/-
      4.6 (15%) mg/mL, FVIII 15.6 +/- 5.4 (44%) IU/mL, FXIII 2.7 +/- 0.7 (6%) IU/mL,
      and plasminogen 1.8 +/- 0.2 (4%) U/mL. In both research and routine settings the
      production process resulted in a consistent product. CONCLUSION: The cryoseal
      manufacturing process resulted in a consistent product, which meets the
      predetermined specifications. The single-donor origin and the absence of
      fibrinolytic inhibitors make cryoseal a good alternative for multidonor and
      autologous fibrin sealants.

PMID- 21880043
TI  - Proteomic analyses of human plasma: Venus versus Mars.
AB  - BACKGROUND: Plasma is vital for the resuscitation of injured patients and to
      restore necessary procoagulants, especially Factors (F)II, FV, FVII, FX, and
      FXIII; however, female plasma has been implicated in the majority of transfusion
      related acute lung injury (TRALI) cases and male-only plasma transfusion regimens
      have significantly decreased the incidence of TRALI. Little is known about the
      human plasma proteome, and no comparisons have been made between male and female
      plasma; therefore, we hypothesize that there are significant differences between
      plasma from male and female donors. STUDY DESIGN AND METHODS: Five units of fresh
      frozen plasma each were collected from nulliparous female donors and male donors,
      and the proteome was analyzed by depleting the 14 most common proteins by
      immunoaffinity columns followed by protein separation by one dimension gel
      electrophoresis, tryptic digestion of the proteins, analysis of the peptides by
      liquid chromatography-tandem mass spectrometry, and identification employing
      human protein sequence databases. RESULTS: Female plasma versus male plasma
      contained pregnancy zone protein (419- to 580-fold), FV (twofold), alpha(1)
      antitrypsin (twofold), beta(2) -microglobulin (twofold), and Complement Factors H
      and C4B (1.5- to 2-fold) at significantly higher concentrations than males and
      males contained significant increases in Fc-binding protein (twofold), protein Z
      dependent protease inhibitor (twofold), phosphatidylinositol glycan-specific
      phospholipase (fourfold), protein S-100 (threefold), and transgelin-2 (14-fold)
      versus females (p < 0.005). The increases in FV, alpha(1)-antitrypsin, and
      beta(2)-microglobulin were confirmed by an activity assay or immunoblots.
      CONCLUSION: We conclude that there are proteomic differences between male and
      female plasma, which could be exploited to improve clinical outcomes in
      transfused patients.

PMID- 21880044
TI  - Storage of thawed plasma for a liquid plasma bank: impact of temperature and
      methylene blue pathogen inactivation.
AB  - BACKGROUND: Rapid transfusion of fresh-frozen plasma (FFP) is desired for
      treating coagulopathies, but thawing and issuing of FFP takes more than 40
      minutes. Liquid storage of plasma is a potential solution but uncertainties exist
      regarding clotting factor stability. We assessed different storage conditions of
      thawed FFP and plasma treated by methylene blue plus light (MB/light) for
      pathogen inactivation. STUDY DESIGN AND METHODS: Fifty thawed apheresis plasma
      samples (approx. 750 mL) were divided into three subunits and either stored for 7
      days at 4 degrees C, at room temperature (RT), and at 4 degrees C after MB/light
      treatment. Clotting factor activities (Factor [F] II, FV, FVII through FXIII,
      fibrinogen, antithrombin, von Willebrand factor antigen, Protein C and S) were
      assessed after thawing and on Days 3, 5, and 7. Changes were classified as
      "minor" (activities within the reference range) and "major" (activities outside
      the reference range). RESULTS: FFP storage at 4 degrees C revealed major changes
      for FVIII (median [range], 56% [33%-114%]) and Protein S (51% [20%-88%]). Changes
      were more pronounced when plasma was stored at RT (FVIII, 59% [37%-123%]; FVII,
      69% [42%-125%]; Protein S, 20% [10%-35%]). MB/light treatment of thawed FFP
      resulted in minor changes. However, further storage for 7 days at 4 degrees C
      revealed major decreases for FVIII (47% [12%-91%]) and Protein S (49% [18%-95%])
      and increases for FVII (150% [48%-285%]) and FX (126% [62%-206%]). CONCLUSION:
      Storage of liquid plasma at 4 degrees C for 7 days is feasible for FFP as is
      MB/light treatment of thawed plasma. In contrast, storage of thawed plasma for 7
      days at RT or after MB/light treatment at 4 degrees C affects clotting factor
      stability substantially and is not recommended.

PMID- 21880045
TI  - Anti-U-like as an alloantibody in S-s-U- and S-s-U+(var)  black people.
AB  - BACKGROUND: S, s, and U antigens belong to the MNS system. They are carried by
      glycophorin B (GPB), encoded by GYPB. Black people with the low-prevalence S-s-
      phenotype, either U- or U+(var), can make a clinically significant anti-U. Anti-U
      like, a cold immunoglobulin G autoantibody quite commonly observed in S-s+U+
      black persons, was previously described to be nonreactive with ficin-, alpha
      chymotrypsin-, and pronase-treated red blood cells (RBCs); nonreactive or weakly
      reactive with papain-treated RBCs; and reactive with trypsin-treated RBCs. Here
      we describe, in S-s- people from different molecular backgrounds, an alloantibody
      to a high-prevalence GPB antigen, which presents the same pattern of reactivity
      with proteases as autoanti-U-like. STUDY DESIGN AND METHODS: Four S-s- patients
      with an alloantibody to a high-prevalence GPB antigen were investigated by
      serologic and molecular methods. RESULTS: An alloantibody was observed in two S-s
      U-/Del GYPB, one S-s-U+(var)/GYPB(P2), and one S-s-U+(var)/GYPB(NY) patients. As
      this alloantibody showed the same pattern of reactivity with proteases as
      autoanti-U-like, we decided to name it "anti-U-like." Anti-U-like made by the two
      S-s-U- patients was reactive with the S-s-U+(var) RBCs of the two other patients.
      CONCLUSION: S-s-U-/Del GYPB, S-s-U+(var)/GYPB(P2), and S-s-U+(var)/GYPB(NY)
      patients can make an alloanti-U-like. Anti-U-like made by S-s-U- people appears
      reactive with GYPB(P2) and GYPB(NY) RBCs, which both express a weak and partial U
      like reactivity. We recommend transfusing S-s-U- RBCs in S-s-U- patients showing
      alloanti-U-like. Our study contributes to a better understanding of
      alloimmunization to GPB in black people and confirms importance of genotyping in
      S-s- patients, especially those with sickle cell disease to be frequently
      transfused.

PMID- 21880046
TI  - Cost-effectiveness of additional blood screening tests in the Netherlands.
AB  - BACKGROUND: During the past decade, blood screening tests such as triplex nucleic
      acid amplification testing (NAT) and human T-cell lymphotropic virus type I or I
      (HTLV-I/II) antibody testing were added to existing serologic testing for
      hepatitis B virus (HBV), human immunodeficiency virus (HIV), and hepatitis C
      virus (HCV). In some low-prevalence regions these additional tests yielded
      disputable benefits that can be valuated by cost-effectiveness analyses (CEAs).
      CEAs are used to support decision making on implementation of medical technology.
      We present CEAs of selected additional screening tests that are not uniformly
      implemented in the EU. STUDY DESIGN AND METHODS: Cost-effectiveness was analyzed
      of: 1) HBV, HCV, and HIV triplex NAT in addition to serologic testing; 2) HTLV
      I/II antibody test for all donors, for first-time donors only, and for pediatric
      recipients only; and 3) hepatitis A virus (HAV) for all donations. Disease
      progression of the studied viral infections was described in five Markov models.
      RESULTS: In the Netherlands, the incremental cost-effectiveness ratio (ICER) of
      triplex NAT is ?5.20 million per quality-adjusted life-year (QALY) for testing
      minipools of six donation samples and ?4.65 million/QALY for individual donation
      testing. The ICER for anti-HTLV-I/II is ?45.2 million/QALY if testing all
      donations, ?2.23 million/QALY if testing new donors only, and ?27.0 million/QALY
      if testing blood products for pediatric patients only. The ICER of HAV NAT is
      ?18.6 million/QALY. CONCLUSION: The resulting ICERs are very high, especially
      when compared to other health care interventions. Nevertheless, these screening
      tests are implemented in the Netherlands and elsewhere. Policy makers should
      reflect more explicit on the acceptability of costs and effects whenever
      additional blood screening tests are implemented.

PMID- 21880047
TI  - Comparison of the in vitro storage properties of Amicus apheresis platelets
      collected using single- and double-needle procedures from the same donors.
AB  - BACKGROUND: Amicus apheresis platelets (PLTs) can be collected using either a
      single- (SN) or a double-needle (DN) procedure. To investigate whether the method
      of PLT collection using the same instrument influences PLT quality, the in vitro
      storage properties of Amicus PLTs were evaluated in the same donors collected by
      SN and DN procedures. STUDY DESIGN AND METHODS: Single apheresis PLT collections
      with concurrent plasma were performed on donors using the Amicus with a target
      yield of 4 * 10(11). A PLT unit was collected from a donor assigned to either a
      SN or a DN procedure; a subsequent donation from the same individual was
      collected by the other procedure (n = 10). Units were stored at 20 to 24 degrees
      C with continuous agitation, assayed for 19 PLT storage variables, and analyzed
      by paired t test, with differences between values obtained with SN and DN
      collections considered significant with p values of less than 0.001. RESULTS: PLT
      units collected by SN procedure had contents and concentrations similar to those
      collected by DN procedures (4.1 * 10(11) +/- 0.3 * 10(11) vs. 4.0 * 10(11) +/-
      0.3 * 10(11) and 1396 * 10(9) +/- 131 * 10(9) vs. 1367 * 10(9) +/- 110 * 10(9)
      PLTs/L). On Day 7, SN and DN PLTs had comparable pH values (7.07 +/- 0.09 vs.
      6.99 +/- 0.17), morphology (52.4 +/- 18.7% vs. 56.0 +/- 13.3% discoid),
      aggregation (87.1 +/- 11.5% vs. 91.3 +/- 5.4%), and activation (45. +/- 11.9% vs.
      48.2 +/- 8.7% CD62P), as well as all other variables (p > 0.05; Day 7 CO(2) , p =
      0.0304). CONCLUSION: The in vitro storage properties of apheresis PLTs collected
      from the same donors using a SN and DN procedure with the Amicus instrument were
      maintained through 7 days of storage and yielded comparable results.

PMID- 21880048
TI  - Serologic characteristics of ceftriaxone antibodies in 25 patients with drug
      induced immune hemolytic anemia.
AB  - BACKGROUND: Ceftriaxone, a third-generation cephalosporin, is commonly used to
      prevent and treat infections. Since 1987, it has been the second most common
      cause of drug-induced immune hemolytic anemia (DIIHA) investigated in our
      laboratory. STUDY DESIGN AND METHODS: Samples from 79 patients (1987-2010),
      suspected of having DIIHA caused by ceftriaxone, were studied for the presence of
      ceftriaxone antibodies. Direct antiglobulin tests (DATs) and tests with
      ceftriaxone-treated red blood cells (RBCs) or untreated and enzyme-treated RBCs
      in the presence of ceftriaxone were performed. RESULTS: Twenty-five (32%) of the
      79 patients had antibodies to ceftriaxone detected. Seventeen (68%) of the 25
      patients were children; reactions in children were usually dramatic and severe.
      Nine (36%) of the 25 patients had fatal DIIHA. Nineteen of the 25 samples had
      DATs performed by our laboratory; 100% of samples were reactive with anti-C3 and
      47% were reactive with anti-IgG. All 25 sera had ceftriaxone antibodies detected
      when testing untreated or ficin-treated RBCs in the presence of ceftriaxone
      (resulting in agglutination, hemolysis or sensitization of test RBCs). These
      antibodies were primarily IgM and reactivity was enhanced by testing ficin
      treated RBCs. Sixteen (64%) of the 25 sera reacted with test RBCs when no
      ceftriaxone was added in vitro; this was most likely due to the transient
      presence of drug or drug-immune complexes in the patient's circulation at the
      time that the blood samples were drawn. CONCLUSION: Ceftriaxone antibodies can
      cause severe intravascular hemolysis. Complement can usually be detected on the
      patient's RBCs and IgM antibodies are usually detected in the patient's serum.

PMID- 21880049
TI  - Trypanosoma cruzi: seroprevalence detected in the blood bank of the Instituto
      Nacional de Pediatria, Mexico City, in the period 2004 through 2009.
AB  - BACKGROUND: The second most common mode of Trypanosoma cruzi or Chagas disease
      transmission is via therapeutic blood transfusion. In Mexico, control of T. cruzi
      is still in its initial phase; in fact, there are only 14 studies published
      covering 10 states on T. cruzi seroprevalence in donated blood in Mexico. Here we
      present the results of 5 years of trypanosomiasis screening in the blood bank of
      the Instituto Nacional de Pediatria. STUDY DESIGN AND METHODS: Samples from all
      blood donated in the period from 2004 to 2009 were analyzed. We screened for T.
      cruzi using an enzyme-linked immunosorbent assay technique. Seropositive samples
      were then processed using the polymerase chain reaction (PCR) to detect a nuclear
      gene segment. RESULTS: A total of 37,333 samples were analyzed and a 0.17% (64
      samples) T. cruzi seroprevalence was found. Donors were mostly from Mexico State
      and Mexico City, which is considered nonendemic for T. cruzi area. Of 64
      seropositive samples, only two tested positive by PCR (3.12%), which amplified a
      189-bp product from nuclear gene from the parasite. CONCLUSION: Although the
      seroprevalence of T. cruzi infection was low, this surveillance program prevented
      the infection of more than 100 children because each unit of blood provides 2.6
      to 3.5 blood products. The majority of the donors were from Mexico State and
      Mexico City, which is a nonendemic area. The serodetection of T. cruzi in this
      region is evidence that is necessary to increase our understanding of its
      distribution in the Mexico City and surrounding places.

PMID- 21880050
TI  - Enumeration of micro-organisms in processed soy products with an automated most
      probable number method compared with standard plate method.
AB  - AIM: The automated TEMPO system (bioMerieux) is based on the most probable number
      (MPN) method for the enumeration of micro-organisms in foods. In this study, we
      evaluated the performance of the TEMPO system as a diagnostic tool in comparison
      with the standard method in processed soy products. METHODS AND RESULTS: A
      verification study was conducted using artificially contaminated soy product
      samples such as soy protein isolate, water-soluble soy polysaccharides, soy milk
      and processed soy food. Five types of micro-organisms were analysed using the
      automated MPN method (total aerobic bacteria, total coliforms,
      Enterobacteriaceae, yeast and mould and Staphylococcus aureus) vs the standard
      plate method. The results from each of the methods were highly correlated (r >
      0.95). Naturally contaminated processed soy products on the market were also
      studied. There were no discrepancies observed between the respective methods.
      CONCLUSIONS: TEMPO methods were equivalent to the corresponding standard plate
      methods with very good rates of agreement. SIGNIFICANCE AND IMPACT OF THE STUDY:
      The automated MPN method is more practical and reliable for in-house
      microbiological testing in processed soy products.

PMID- 21880051
TI  - Assessment and modification of degenerate qPCR primers that amplify functional
      genes from etheneotrophs and vinyl chloride-assimilators.
AB  - AIMS: Degenerate qPCR primer sets that target the functional genes etnC and etnE
      in etheneotrophs and vinyl chloride-assimilating bacteria were assessed and
      modified in an effort to improve performance. METHODS AND RESULTS: Functional
      gene abundance in four pure cultures was estimated by qPCR using novel (MRTC and
      MRTE) and existing (RTC and RTE) degenerate primer sets and compared to
      abundances estimated with nondegenerate gene-specific primers (GSPs). Functional
      gene abundance in groundwater DNA extracted from several contaminated sites was
      also estimated with MRTC and MRTE primers. CONCLUSIONS: MRTC primers displayed
      significantly improved etnC quantification in both pure cultures and
      environmental samples. SIGNIFICANCE AND IMPACT OF THE STUDY: Application of MRTC
      and MRTE primer sets will enhance microbial ecology studies involving
      etheneotrophs and qPCR analyses that support vinyl chloride bioremediation
      strategies.

PMID- 21880052
TI  - Watch what you lick!

PMID- 21880053
TI  - Myxoma of the ear lobe in a 23-month-old girl with Carney complex.
AB  - Myxomas of the ear are extremely uncommon, especially in young children. A 23
      month-old girl born to a family with known Carney complex, a condition that
      predisposes to multiple myxomas, presented with a large, cauliflower-like mass
      located on the back of her right ear. Histopathologically, the lesion was
      composed of scattered spindle-shaped or stellate cells with abundant associated
      mucin and a very sparse inflammatory infiltrate containing lymphocytes and
      neutrophils. The patient was a carrier of a protein kinase A regulatory subunit
      1A (PRKAR1A) mutation; PRKAR1A mutations cause Carney complex in most patients
      with this rare disorder. This is the earliest presentation of an ear lobe myxoma
      reported in the literature.

PMID- 21880055
TI  - Getting the fundamentals of movement: a meta-analysis of the effectiveness of
      motor skill interventions in children.
AB  - The development of fundamental movement skills (FMS) is associated with positive
      health-related outcomes. Children do not develop FMS naturally through
      maturational processes. These skills need to be learned, practised and
      reinforced. The objective was to determine the effectiveness of motor skill
      interventions in children. The following databases were searched for relevant
      articles: Academic Search Premier, PsycArticles, PsycInfo, SportDiscus and ERIC.
      No date range was specified and each search was conducted to include all possible
      years of publication specific to each database. Key terms for the search included
      motor, skill, movement, intervention, programme or children. Searches were
      conducted using single and combined terms. Pertinent journals and article
      reference lists were also manually searched. INCLUSION CRITERIA: (1)
      implementation of any type of motor skill intervention; (2) pre- and post
      qualitative assessment of FMS; and (3) availability of means and standard
      deviations of motor performance. A significant positive effect of motor skill
      interventions on the improvement of FMS in children was found (d= 0.39, P <
      0.001). Results indicate that object control (d= 0.41, P < 0.001) and locomotor
      skills (d= 0.45, P < 0.001) improved similarly from pre- to post-intervention.
      The overall effect size for control groups (i.e. free play) was not significant
      (d= 0.06, P= 0.33). A Pearson correlation indicated a non-significant (P= 0.296),
      negative correlation (r=-0.18) between effect size of pre- to post-improvement of
      FMS and the duration of the intervention (in minutes). Motor skill interventions
      are effective in improving FMS in children. Early childhood education centres
      should implement 'planned' movement programmes as a strategy to promote motor
      skill development in children.

PMID- 21880054
TI  - The financial and psychological impacts on mothers of children with chronic
      fatigue syndrome (CFS/ME).
AB  - BACKGROUND: Paediatric chronic fatigue syndrome or myalgic encephalopathy
      (CFS/ME) is relatively common and children can be severely affected attending
      little or no school for extended periods. There are no studies quantifying the
      financial impact of having a child with CFS/ME and there is little information of
      the impact on parental mood. METHODS: Forty mothers of children with CFS/ME from
      a regional specialist CFS/ME service completed inventories to assess their
      psychological well-being (Hospital Anxiety and Depression Scale, General Health
      Questionnaire-12) loss of earnings and increased expenditure. In addition, eight
      mothers took part in a semi-structured qualitative interview. RESULTS: Most
      parents of children with CFS/ME experience loss of monthly income (mean = L247)
      and increase in monthly expenditure (mean = L206). Twenty-eight (72%) mothers
      were above the cut-off for the General Health Questionnaire-12 compared with 20%
      in the healthy population (95% CI 55, 85, P < 0.001) suggesting they probably
      have a mental health problem. This may be explained by the qualitative interviews
      where mothers described five areas contributing to poor parental health: lack of
      understanding from others; marital tension; concern about their child's distress;
      concern about the impact on siblings and emotional distress causing physical
      symptoms. CONCLUSIONS: The majority of families of children with CFS/ME
      experience decreased income and increased expenditure with a marked impact on
      maternal psychological health. Clinicians need to be aware of this to provide
      appropriate support to families who care for children with CFS/ME.

PMID- 21880056
TI  - Strategies for improving disability awareness and social inclusion of children
      and young people with cerebral palsy.
AB  - BACKGROUND: Children and youth with disabilities are at a higher risk of being
      socially excluded or bullied while at school compared with their typically
      developing peers. This study explored disabled children's suggestions for
      improving social inclusion. METHODS: Fifteen children with cerebral palsy were
      interviewed or took part in a group discussion about social inclusion and
      bullying. All interviews and focus groups were audio-recorded and transcribed
      verbatim. RESULTS: The children and youth described several strategies to help
      improve social inclusion at school including: (1) disclosure of condition and
      creating awareness of disability; (2) awareness of bullying; (3) developing a
      peer support network and building self-confidence; and (4) suggestions on what
      teachers can do. CONCLUSIONS: It is recommended that children's suggestions be
      considered within the classroom context to enhance the social inclusion and
      participation of children with disabilities.

PMID- 21880057
TI  - Handling of radical prostatectomy specimens: total embedding with whole mounts,
      with special reference to the Ancona experience.

PMID- 21880058
TI  - Systematic ethnography of school-age children with bleeding disorders and other
      chronic illnesses: exploring children's perceptions of partnership roles in
      family-centred care of their chronic illness.
AB  - PURPOSE: In this qualitative study, school-age children between 7 and 11 years,
      living with a bleeding disorder or other chronic illness, defined how they
      understand their partnership role in family-centred care (FCC), and recommended
      FCC strategies. METHODS: This systematic ethnography had three phases:
      unstructured interviews explored how children understood FCC partnership roles
      (phase I); document review provided FCC institutional context (phase II); and
      validation interviews generated FCC partnership recommendations (phase III). This
      study took place within the area served by a Western Canadian children's
      hospital. Interviews were held at the hospital or children's home. In phase I,
      purposive sampling was used to recruit children receiving outpatient care for a
      bleeding disorder (n = 4) or another chronic illness (n = 4). In phase II,
      policies and legislation were compared with how children understand their FCC
      partnership role. In phase III, validation interviews were conducted with
      children (n = 3) to confirm domains and generate FCC supporting strategies. Data
      collection and analysis were based on domain analysis and qualitative
      ethnographic content analysis. RESULTS: Phase I outcomes included seven domains
      regarding how children understood their role as partners in FCC: my best
      interests, virtues, talking and listening, being involved, knowing, making
      decisions and being connected. Phase II outcomes revealed how these domains were
      represented in institutional contexts. Phase III outcomes confirmed domains and
      generated key strategies to support children's role as FCC partners through
      graphic representation of FCC as a treasure map, interactive workshop and online
      game. CONCLUSIONS: School-age children, living with a bleeding disorder or other
      chronic illness, similarly want to learn how to be FCC partners by developing
      competence as healthcare team members, identifying their own best interests,
      learning how to communicate with 'grown-ups', clarifying roles and goals, and
      guided opportunities for decision making. Facilitating school-age children's FCC
      partnership roles is worthy to explore in youth transition programmes.

PMID- 21880059
TI  - Prognostic tissue markers in melanoma.
AB  - Prognostic tissue markers in melanoma Prognosis for patients diagnosed with
      cutaneous melanoma is currently based upon histopathological features alone,
      although tumours which are morphologically similar can behave differently.
      Numerous putative biomarkers have been identified in an attempt to aid
      prognostication for primary melanoma, using methods which include
      immunhistochemistry, polymerase chain reaction (PCR), array comparative genomic
      hybridization (CGH) and gene expression arrays. Despite this wide body of
      research, no biomarkers for prognosis in melanoma have been translated or are
      close to translation into clinical practice. In this review selected prognostic
      biomarkers are evaluated and the factors influencing successful biomarker
      translation, including phases of biomarker development and study design, are
      explored in an attempt to highlight the current gap between prognostic melanoma
      biomarker research and clinical translation.

PMID- 21880060
TI  - Effects of breast health education conducted by trained breast cancer survivors.
AB  - AIMS:   This article is a report on a study of the effectiveness of breast health
      education provided by trained breast cancer survivors on knowledge, skills,
      performance and self-efficacy. BACKGROUND:   Numerous studies have been performed
      to assess the effects of breast health education provided by health
      professionals, but few studies have examined the effects of education provided by
      lay persons, such as breast cancer survivors. This study focused on the role of
      breast cancer survivors as breast health educators. METHODS:   A pretest and post
      test quasi-experimental design was used. Trained breast cancer survivors
      conducted a 60-minute breast health class that was guided by self-efficacy theory
      to young healthy women. The data were collected in 2008 from 22 young healthy
      women who participated in the class. Self-report questionnaires were used to
      measure the breast cancer and breast self-examinations knowledge, skills,
      performance and self-efficacy at pre-education, and at 1 month and 3 months post
      education. RESULTS:   The scores on knowledge, skills, performance and self
      efficacy before breast health education were significantly increased after 1
      month and 3 months post-education. CONCLUSION:   The results of this study
      demonstrate that a one-time breast health class provided by trained breast cancer
      survivors can be useful in motivating young women to adopt behaviours that help
      to prevent breast cancer morbidity and mortality.

PMID- 21880061
TI  - Skeleton pattern and joint formation in chorioallantoic grafts containing the
      distal parts of the chick wing bud.
AB  - Skeleton pattern formation was examined in chick wing bud grafts using the
      chorioallantoic grafting method. The distal parts of the wing bud were excised
      from the donor wing and transplanted onto the chorioallantoic membrane (the
      experimental groups). Transplants with intact limb bud material served as the
      control group. The skeleton pattern formation in the grafts depended on the
      amount of transplanted material and donor's limb bud stage. The younger the
      donor's stage and the bigger the piece of the transplanted material the more
      proximal parts grafts had, more retarded growth and abnormal skeleton in the
      zeugopod and autopod was. The percentage of the signs of insufficient blood
      supply in the experimental groups was less than that in the control group. As the
      amount of the transplanted limb bud material decreased and donor's limb bud aged,
      post-axial polydactyly changed to the pre-axial one.

PMID- 21880062
TI  - Close, impinging and overriding spinous processes in the thoracolumbar spine: the
      relationship between radiological and scintigraphic findings and clinical signs.
AB  - REASONS FOR PERFORMING STUDY: There has been no objective study comparing
      radiological features of spinous processes (SPs) in the thoracolumbar region
      and/or scintigraphic findings with clinical signs. OBJECTIVES: To investigate the
      relationship between the presence or absence of clinical signs of back pain and:
      1) radiological findings of close, impinging or overriding SPs; 2) increased
      radiopharmaceutical uptake (IRU) in the SPs; and 3) the combination of
      radiological findings and IRU. Also to determine the prevalence of concurrent
      osseous pathology. METHODS: Five-hundred and eighty-two horses, presented for
      perceived back pain and poor performance, underwent comprehensive clinical
      investigation including diagnostic analgesia of the forelimbs, hindlimbs, back
      and sacroiliac joints, and radiographic and scintigraphic evaluation of the
      thoracolumbar spine. Radiological and scintigraphic grades were determined
      subjectively. Statistical analysis was performed to determine the relationships
      between clinical signs of back pain, radiological and scintigraphic features,
      age, breed, gender, discipline, height and weight. RESULTS: Thoroughbreds (TBs)
      were over-represented with thoracolumbar pain compared with Warmbloods and TB
      cross breeds. There was a significant association between maximum and total
      radiological grades of the SPs and thoracolumbar pain, between maximum and total
      grades of IRU and thoracolumbar pain, and between a combination of radiological
      and scintigraphic abnormalities and thoracolumbar pain. Horses with
      osteoarthritis (OA) of the synovial intervertebral articulations (SIAs) were more
      likely to have thoracolumbar pain than horses with lesions of the SPs alone, but
      the presence of OA of the SIAs and lesions of the SPs was associated with the
      highest likelihood of thoracolumbar pain. CONCLUSIONS AND POTENTIAL RELEVANCE:
      Fore- or hindlimb lameness and/or pain associated with the sacroiliac joints
      could mimic primary thoracolumbar pain. A combination of radiology and
      scintigraphy gives the most accurate prediction of thoracolumbar pain, but
      diagnostic analgesia is crucial for accurate diagnosis.

PMID- 21880063
TI  - A systematic review of the efficacy of interventions for dynamic intermittent
      dorsal displacement of the soft palate.
AB  - There are numerous treatments for correction of dorsal displacement of the soft
      palate (DDSP). However, the efficacy of these treatments is controversial and
      there is little consensus on how best to treat this condition. The aims of this
      study were to systematically review the literature and to assess the evidence on
      the clinical effects of interventions for dynamic intermittent DDSP. A secondary
      objective was to assess whether factors relating to study quality affected
      reported success rates. Twenty-three studies were included, covering a wide
      number of interventions but also differing widely is terms of study design,
      sample size, method of diagnosis, outcome measure and the number lost to follow
      up. The assessment of adverse effects was severely limited because of lack of
      reporting. The way in which success is measured appears to have a great effect on
      the reported results. Research synthesis has been severely limited because of the
      heterogeneity in the included studies. The low level of evidence makes it
      difficult to draw firm conclusions as to the efficacy of procedures for DDSP.
      Hence it is currently not possible to determine which procedure is the most
      appropriate. This systematic review highlights the difficulties of studying
      palatal dysfunction and suggests areas where improvements can be made in future
      studies.

PMID- 21880064
TI  - Is a single force plate adequate for stabilographic analysis in horses?
AB  - REASONS FOR PERFORMING STUDY: Postural balance can be quantified using
      stabilographic variables derived from force plate data that describe movements of
      the horse's centre of pressure (COP) in the horizontal plane. Most force plates
      are not large enough to accommodate all 4 limbs of a standing horse, so the study
      was designed to assess whether representative stabilographic data could be
      collected from the forelimbs or hindlimbs. OBJECTIVE: To determine whether
      stabilographic data from either the forelimbs or the hindlimbs were
      representative of data for the total body. METHODS: Stabilographic data (960 Hz)
      were collected from 17 sound horses standing with the forelimbs and the hindlimbs
      on separate force plates. To increase variability in the data, horses were of
      different sizes, the recording duration was varied (15-60 s) and data were
      collected under sighted and blindfolded conditions. RESULTS: Correlation matrices
      indicated that total body stabilographic variables were highly significantly
      correlated with both forelimb and hindlimb data but correlation coefficients were
      higher for forelimb data. Forward stepwise regression selected forelimb data for
      inclusion in the model for 15/16 variables, the exception being mean absolute
      mediolateral velocity. CONCLUSIONS: Ground reaction force data from a pair of
      limbs, preferably the forelimbs, can be used to measure variables that represent
      total body postural balance in sound standing horses. POTENTIAL RELEVANCE:
      Stabilographic data from either the forelimbs or hindlimbs may be useful for
      detecting and quantifying deficiencies in postural balance in ataxic horses.

PMID- 21880065
TI  - Possible role of carpal hyperextension in superficial digital flexor
      tendinopathy.
AB  - REASONS FOR PERFORMING STUDY: The specific biomechanical circumstances that
      induce excessive superficial digital flexor tendon (SDFT) strain in horses are
      unknown. HYPOTHESIS: Carpal joint hyperextension during axial limb loading during
      the middle of stance disproportionately enhances SDFT strains compared to
      suspensory ligament (SL) strains. METHODS: Superficial digital flexor tendon and
      SL strains were measured in 7 cadaver limbs during in vitro loading that
      maintained carpal extension or allowed carpal hyperextension by constraining, or
      allowing rotation of, the radius during loading conditions that simulated the
      middle of stance at the walk. The effect of carpal hyperextension on SDFT and SL
      strains and joint angles was assessed using repeated measures ANOVA. RESULTS:
      Limb loading generally resulted in higher SL strains than SDFT strains for both
      carpal extension and hyperextension loading conditions. Compared to carpal
      extension, carpal hyperextension resulted in increased strains in both the SDFT
      and the SL; however, a greater increase in strain was seen in the SDFT. On
      average, carpal hyperextension caused approximately 3 degrees  greater carpal
      extension, 1 degrees  greater metacarpophalangeal joint hyperextension, 1 degrees
      greater proximal interphalangeal joint flexion and <1 degrees  greater distal
      interphalangeal joint flexion than did carpal extension. CONCLUSIONS AND CLINICAL
      RELEVANCE: Carpal joint hyperextension is likely to induce disproportionately
      higher strain in the SDFT than in the SL. Factors that affect carpal stability
      are likely to affect the risk for superficial digital flexor tendinopathy.

PMID- 21880066
TI  - Influence of surface treatments on the flexural strength of denture base repair.
AB  - OBJECTIVE: The purpose of this study was to evaluate the flexural strength of
      repairs made with autopolymerising acrylic resin after different treatments of
      joint surfaces. MATERIAL AND METHODS: Fifty rectangular specimens were made with
      heat-polymerised acrylic resin and 40 were repaired with autopolymerising acrylic
      resin following joint surface treatments: group 1 (intact specimens), group 2
      (chemical treatment: wetting with methyl-methacrylate for 180 s), group 3
      (abraded with silicon carbide paper), group 4 (abraded and wetting with methyl
      methacrylate for 180 s) and group 5 (without surface treatment). The flexural
      strength was measured by a three-point bending test using a universal testing
      machine with a 100 Kgf load cell in the centre of repair at 5 mm/min cross-head
      speed. All data were analysed using one-way anova and Tukey HSD test for multiple
      comparisons (p < 0.05). RESULTS: Among repaired specimens, groups 2 and 4 had
      66.53 +/- 3.4 and 69.38 +/- 1.8 MPa mean values and were similar. These groups
      had superior flexural strength than groups 3 and 5 that were similar and had
      54.11 +/- 3.4 and 51.24 +/- 2.8 MPa mean values, respectively. Group 1 had a mean
      value of 108.30 +/- 2.8 MPa being the highest result. CONCLUSION: It can be
      concluded that the treatment of the joint surfaces with methyl-methacrylate
      increases the flexural strength of denture base repairs, although the strength is
      still lower than that observed for the intact denture base resin. Abrasion with
      sandpaper was not able to influence the flexural strength of repaired denture
      bases.

PMID- 21880067
TI  - Pharmacogenetics and pharmacogenomics of thienopyridines: clinically relevant?
AB  - Pharmacogenetics have been touted as the future of personalized medicine where
      genetic biomarkers will guide therapeutic approach. The currently approved
      thienopyridines, prasugrel and clopidogrel, are prodrugs requiring conversion to
      active metabolite through the cytochrome P450 system. Genetic variation has been
      associated with the pharmacokinetic, pharmacodynamic, and clinical response to
      clopidogrel, but not to prasugrel. This review aims to summarize the recent
      pharmacogenetic findings associated with the response to thienopyridine
      treatment. Additionally, considerations for the incorporation of genetic
      biomarkers into clinical practice will be discussed in the context of
      thienopyridines.

PMID- 21880068
TI  - Comparison between oscillometric and invasive blood pressure measurements in
      critically ill premature infants.
AB  - AIM: Blood pressure (BP) measurement techniques in neonates generally involve
      noninvasive measurements with a cuff (oscillometric) or invasive measurements
      through an arterial catheter. The aim of this study was to determine the
      reliability of the noninvasive oscillometric method in critically ill preterm
      infants when results were compared with the invasive technique. METHOD: Twenty
      seven premature infants with a mean birth weight of 1138 +/- 552 g were enrolled
      in the prospective study. Invasive and noninvasive mean arterial pressure (MAP)
      levels were recorded simultaneously at each measurement in all patients. Low or
      lower range mean invasive MAP values (MAP <=30) were evaluated separately as we
      aimed to assess the value of noninvasive measurements in hypotensive sick
      premature infants. RESULTS: Totally, 431 paired BP measurements were taken during
      the first week of life. There was no statistically significant difference between
      invasive and noninvasive readings. However, noninvasive measurements were found
      significantly higher compared with invasive measurements in the presence of
      hypotension (p < 0.05). CONCLUSION: This study showed good agreement between
      oscillometric and invasive readings in critically ill premature infants, and
      further, comparable mean MAP values were found with the two methods. However, the
      accuracy of the oscillometric BP measurement technique fails in preterm infants
      with BP within the lower limits.

PMID- 21880069
TI  - Effect of oral hepatocyte growth factor gene mediated by attenuated salmonella on
      2-, 4-, 6-trinitro-benzene-sulfonic-acid-induced ulcerative colitis in rat.
AB  - BACKGROUND AND AIM: In order to explore a new therapeutic method, we investigated
      the effects of exogenously expressed hepatocyte growth factor mediated by
      attenuated salmonella (TPH) on rats with ulcerative colitis (UC) induced by 2-, 4
      , 6-trinitro-benzene-sulfonic acid. METHODS: The UC rats were treated with TPH,
      attenuated salmonella with a eukaryotic expression vector (TP) or sodium
      bicarbonate (model control [MC]) every other day. Cluster of differentiation
      (CD)4(+) and CD8(+) T cells and immunoglobulins in the blood were analyzed by
      flow cytometry. The HGF expression was determined by immunohistochemistry. A
      macroscopic-scale observation of the colon and a histological assessment were
      also carried out. RESULTS: The CD4(+) T counts and the CD4(+) /CD8(+) ratio in
      the TPH group were significantly lower than that in the MC group. The
      immunoglobulin M and immunoglobulin G(1) levels in the TPH group were
      significantly lower than that in the MC group and TP group. After treatment with
      TPH, the symptoms of the ulcerative rats were significantly alleviated. The
      colonic lesion grades in the TPH group were lower than that in the TP group and
      MC group. Significant improvement occurred after the TPH treatment, as evidenced
      by alleviated mucosal inflammation. At 7 days post-treatment, the HGF expression
      in the colonic tissues that were treated with TPH was stronger than that in the
      samples treated with TP. CONCLUSIONS: TPH inhibits the proliferation of T
      lymphocytes and the antibody production of B lymphocytes. Furthermore, it
      ameliorates mucosal inflammation and promotes the regeneration of mucosa and the
      healing of the colonic ulceration.

PMID- 21880070
TI  - Retrograde arterial flush of the liver graft in living donor liver
      transplantation may ameliorate post-transplantational cholestasis--prospective
      randomized study.
AB  - Retrograde arterial flush (RGAF) of liver grafts, which prevents arterial intima
      injuries in living donor liver transplantation (LDLT), seemed to reduce post
      transplantational cholestasis by our preliminary study. The aim of this study was
      to further confirm this effect of RGAF of grafts in LDLT by a prospective
      randomized study. The enrolled cases were randomly divided into two groups, RGAF
      (portal flush plus RGAF) and non-RGAF (portal flush only). The outcome measures
      included intra-operative hemodynamic changes, one-month post-transplantational
      liver function tests and acute cellular rejection, vascular and biliary
      complications, the length of postoperative hospital stay, and graft and patient
      survivals. The significant findings of results were lower postoperative serum
      bilirubin in the RGAF group until three wk after transplantation (days 1, 3, 7,
      14, and 21 serum total bilirubin, mg/dL: 5.82+/-5.46, 3.95+/-4.28, 4.87+/-5.01,
      3.62+/-5.32, and 3.63+/-6.91 vs. 8.41+/-5.49, 7.47+/-5.61, 10.0+/-10.1, 9.06+/
      11.6, and 6.02+/-9.84, respectively, in RGAF and non-RGAF, p=0.017, 0.002, 0.014,
      0.011, 0.109) and shorter postoperative hospital stay in the RGAF group (31.1+/
      17.6 vs. 44.8+/-32.3 d, respectively, in RGAF and non-RGAF, p=0.035). In
      conclusion, the RGAF of liver grafts on a back table may ameliorate postoperative
      functional cholestasis in LDLT, which possibly reduces postoperative hospital
      stay.

PMID- 21880071
TI  - In vivo effect of bone marrow-derived mesenchymal stem cells in a rat kidney
      transplantation model with prolonged cold ischemia.
AB  - Brain death and prolonged cold ischemia are major contributors to the poorer long
      term outcome of transplants from deceased donor kidney transplants, with an even
      higher impact if expanded criteria donors ('marginal organs') are used. Targeting
      ischemia-reperfusion injury-related intragraft inflammation is an attractive
      concept to improve the outcome of those grafts. As mesenchymal stem cells (MSCs)
      express both immunomodulatory and tissue repair properties, we evaluated their
      therapeutic efficacy in a rat kidney transplant model of prolonged cold ischemia.
      The in vitro immunomodulatory capacity of bone marrow-derived rat MSCs was tested
      in co-cultures with rat lymph node cells. For in vivo studies, Dark Agouti rat
      kidneys were cold preserved and transplanted into Lewis rats. Syngeneic Lewis
      MSCs were administered intravenously. Transplants were harvested on day 3, and
      inflammation was examined by quantitative RT-PCR and histology. Similarly to MSCs
      from other species, rat MSCs in vitro also showed a dose-dependent
      immunomodulatory capacity. Most importantly, in vivo administration of MSCs
      reduced the intragraft gene expression of different pro-inflammatory cytokines,
      chemokines, and intercellular adhesion molecule-1. In addition, fewer antigen
      presenting cells were recruited into the renal allograft. In conclusion, rat MSCs
      ameliorate inflammation induced by prolonged cold ischemia in kidney
      transplantation.

PMID- 21880072
TI  - Elimination of norovirus in a chronic carrier under immunosuppression after heart
      transplantation--effect of everolimus.

PMID- 21880073
TI  - A nationwide cohort study of the risk of chronic obstructive pulmonary disease in
      coeliac disease.
AB  - OBJECTIVE: Chronic obstructive pulmonary disease (COPD) continues to be an
      important cause of morbidity, mortality and healthcare costs in the western
      world. Although smoking is an important trigger of COPD, other factors such as
      chronic inflammation and malnutrition are known to influence its development.
      Because coeliac disease (CD) is characterized both by dysregulated inflammation
      and malnutrition, the possibility of an association between CD and COPD was
      investigated. METHODS: Through biopsy data from all Swedish pathology
      departments, we identified 10 990 individuals with CD who were biopsied between
      1987 and 2008 (Marsh 3: villous atrophy). As controls, 54 129 reference
      individuals matched for age, sex, county and calendar year of first biopsy were
      selected. Cox regression analysis was then performed to estimate hazard ratios
      (HRs) for having a diagnosis of COPD according to the Swedish Patient Register.
      RESULTS: During follow-up, 380 individuals with CD (3.5%) and 1391 (2.6%)
      controls had an incident diagnosis of COPD, which corresponds to an HR of 1.24
      (95% CI: 1.10-1.38) and an excess risk of COPD of 79/100 000 person-years in CD.
      The risk increase remained 5 years after biopsy (HR = 1.17; 95% CI: 1.00-1.37).
      Risk estimates did not change with adjustment for type 1 diabetes, thyroid
      disease, rheumatoid arthritis, country of birth or level of education. Men with
      CD were at a higher risk of COPD (HR = 1.39; 95% CI: 1.18-1.62) than women with
      CD (HR = 1.11; 95% CI: 0.94-1.30). Of note, CD was also associated with COPD
      before CD diagnosis (odds ratio = 1.22; 95% CI: 1.02-1.46). Conclusion.  Patients
      with CD seem to be at a moderately increased risk of COPD both before and after
      CD diagnosis.

PMID- 21880074
TI  - Genetic polymorphisms in oestrogen receptor-binding sites affect clinical
      outcomes in patients with prostate cancer receiving androgen-deprivation therapy.
AB  - BACKGROUND: Accumulating evidence indicates that oestrogens have significant
      direct effects on normal prostate development and carcinogenesis. The majority of
      the biological activities of oestrogens are mediated through the oestrogen
      receptor (ER), which functions as a hormone-inducible transcription factor to
      regulate target gene expression by binding to oestrogen response elements (EREs)
      in the regulatory regions of target genes. Sequence variants in EREs might affect
      the ER-ERE interaction and subsequent physiological activities. Therefore, we
      tested whether common single-nucleotide polymorphisms (SNPs) inside EREs are
      related to the clinical outcomes of androgen-deprivation therapy (ADT) in men
      with prostate cancer. METHODS: We systematically evaluated 49 ERE SNPs predicted
      using a genome-wide database in a cohort of 601 men with advanced prostate cancer
      treated with ADT. The prognostic significance of these SNPs on disease
      progression, prostate cancer-specific mortality (PCSM) and all-cause mortality
      (ACM) after ADT was assessed using Kaplan-Meier analysis and a Cox regression
      model. RESULTS: Based on multiple hypothesis testing, BNC2 rs16934641 was found
      to be associated with disease progression; in addition, TACC2 rs3763763 was
      associated with PCSM, and ALPK1 rs2051778 and TACC2 rs3763763 were associated
      with ACM. These SNPs remained significant in multivariate analyses that included
      known clinicopathological predictors. Moreover, a combined genotype effect on ACM
      was observed when ALPK1 rs2051778 and TACC2 rs3763763 were analysed in
      combination. Patients with a greater number of unfavourable genotypes had a
      shorter time to ACM during ADT (P for trend <0.001). CONCLUSION: The
      incorporation of ERE SNPs into models with known predictors might improve outcome
      prediction in patients with prostate cancer receiving ADT.

PMID- 21880075
TI  - Dynamic evolution of herbivore-induced sesquiterpene biosynthesis in sorghum and
      related grass crops.
AB  - Sorghum (Sorghum bicolor) plants damaged by insects emit a blend of volatiles,
      predominantly sesquiterpenes, that are implicated in attracting natural enemies
      of the attacking insects. To characterize sesquiterpene biosynthesis in sorghum,
      seven terpene synthase (TPS) genes, SbTPS1 through SbTPS7, were identified based
      on their evolutionary relatedness to known sesquiterpene synthase genes from
      maize and rice. While SbTPS6 and SbTPS7 encode truncated proteins, all other TPS
      genes were determined to encode functional sesquiterpene synthases. Both SbTPS1
      and SbTPS2 produced the major products zingiberene, beta-bisabolene and beta
      sesquiphellandrene, but with opposite ratios of zingiberene to beta
      sesquiphellandrene. SbTPS3 produced (E)-alpha-bergamotene and (E)-beta-farnesene.
      SbTPS4 formed (E)-beta-caryophyllene as the major product. SbTPS5 produced mostly
      (E)-alpha-bergamotene and (Z)-gamma-bisabolene. Based on the genome sequences of
      sorghum, maize and rice and the sesquiterpene synthase genes they contain,
      collinearity analysis identified the orthologs of sorghum sesquiterpene synthase
      genes, except for SbTPS4, in maize and rice. Phylogenetic analysis implied that
      SbTPS1, SbTPS2 and SbTPS3, which exist as tandem repeats, evolved as a
      consequence of local gene duplication in a lineage-specific manner. Structural
      modeling and site-directed mutagenesis experiments revealed that three amino
      acids in the active site play critical roles in defining product specificity of
      SbTPS1, SbTPS2, SbTPS3 and their orthologs in maize and rice. The naturally
      occurring functional variations of sesquiterpene synthases within and between
      species suggest that multiple mechanisms, including lineage-specific gene
      duplication, subfunctionalization, neofunctionalization and pseudogenization of
      duplicated genes, have all played a role in the dynamic evolution of insect
      induced sesquiterpene biosynthesis in grasses.

PMID- 21880076
TI  - The rice transcription factor IDEF1 directly binds to iron and other divalent
      metals for sensing cellular iron status.
AB  - Iron is essential for most living organisms and its availability often determines
      survival and proliferation. The Oryza sativa (rice) transcription factor IDEF1
      plays a crucial role in regulating iron deficiency-induced genes involved in iron
      homeostasis. In the present report, we found characteristic histidine-asparagine
      repeat and proline-rich regions in IDEF1 and its homolog in Hordeum vulgare
      (barley), HvIDEF1. An immobilized metal ion affinity chromatography assay
      revealed that IDEF1 and HvIDEF1 bind to various divalent metals, including Fe(2+)
      and Ni(2+) . Recombinant IDEF1 protein expressed in Escherichia coli contained
      mainly Fe and Zn. This metal-binding activity of IDEF1 was almost abolished by
      deletion of the histidine-asparagine and proline-rich regions, but DNA-binding
      and trans-activation functions were not impaired by the deletion. Transgenic rice
      plants constitutively overexpressing IDEF1 without these metal-binding domains
      failed to cause pleiotropic effects conferred by overexpression of full-length
      IDEF1, including a low germination rate, impaired seedling growth, tolerance to
      iron deficiency in hydroponic culture, and enhanced expression of various iron
      deficiency-inducible genes. Impairment of the transcriptional regulation of IDEF1
      by deletion of the metal-binding domains occurred primarily at an early stage of
      iron deficiency. These results suggest that the histidine-asparagine and proline
      rich regions in rice IDEF1 directly bind to divalent metals and sense the
      cellular metal ion balance caused by changes in iron availability.

PMID- 21880078
TI  - Cucumber mosaic virus suppressor 2b binds to AGO4-related small RNAs and impairs
      AGO4 activities.
AB  - Cucumber mosaic virus suppressor 2b (CMV2b) is a nuclear viral suppressor that
      interferes with local and systemic silencing and inhibits AGO1 slicer activity.
      CMV2b-mediated transgene hypomethylation and its localization in Cajal bodies
      suggests a role of CMV2b in RNA-directed DNA methylation (RdDM). However, its
      direct involvement in RdDM, or its binding with small RNAs (sRNAs) in vivo is not
      yet established. Here, we show that CMV2b binds both microRNAs (miRNAs) and small
      interfering RNAs (siRNAs) in vivo. sRNA sequencing data from the CMV2b
      immunocomplex revealed its preferential binding with 24-nt repeat-associated
      siRNAs. We provide evidence that CMV2b also has direct interaction with the AGO4
      protein by recognizing its PAZ and PIWI domains. Subsequent analysis of AGO4
      functions revealed that CMV2b reduced AGO4 slicer activity and the methylation of
      several loci, accompanied by the augmented accumulation of 24-nt siRNAs in
      Arabidopsis inflorescences. Intriguingly, CMV2b also regulated an AGO4-related
      epiallele independently of its catalytic potential, which further reinforces the
      repressive effects of CMV2b on AGO4 activity. Collectively, our results
      demonstrate that CMV2b can counteract AGO4-related functions. We propose that by
      adopting novel counter-host defense strategies against AGO1 and AGO4 proteins,
      CMV creates a favorable cellular niche for its proliferation.

PMID- 21880079
TI  - A mixed-methods evaluation of complementary therapy services in palliative care:
      yoga and dance therapy.
AB  - To inform service provision and future research, we evaluated two complementary
      therapy services: yoga classes and dance therapy [The Lebed Method (TLM)]. Both
      were run as 6-week group courses. Patients completed the Measure Yourself
      Concerns and Wellbeing questionnaire pre- and post-course. Mean change over time
      was calculated for patient-nominated concern and well-being scores. Qualitative
      data regarding factors affecting health other than the therapy and benefits of
      the service were analysed using content analysis. Eighteen patients participated
      (mean age 63.8 years; 16 female; 14 cancer diagnoses); 10 were doing yoga, five
      TLM, and three both yoga and TLM; 14 completed more than one assessed course.
      Patients' most prevalent concerns were: mobility/fitness (n= 20), breathing
      problems (n= 20), arm, shoulder and neck problems (n= 18), difficulty relaxing
      (n= 8), back/postural problems (n= 8), fear/anxiety (n= 5). Factors affecting
      patients' health other than the therapy were prevalent and predominantly negative
      (e.g. treatment side effects). Patients reported psycho-spiritual, physical and
      social benefits. Concern scores improved significantly (P < 0.001) for both
      therapies; improved well-being was clinically significant for yoga. Evaluations
      of group complementary therapy services are feasible, can be conducted
      effectively and have implications for future research. Yoga and TLM may be of
      benefit in this population.

PMID- 21880077
TI  - A tomato LysM receptor-like kinase promotes immunity and its kinase activity is
      inhibited by AvrPtoB.
AB  - Resistance in tomato (Solanum lycopersicum) to infection by Pseudomonas syringae
      involves both detection of pathogen-associated molecular patterns (PAMPs) and
      recognition by the host Pto kinase of pathogen effector AvrPtoB which is
      translocated into the host cell and interferes with PAMP-triggered immunity
      (PTI). The N-terminal portion of AvrPtoB is sufficient for its virulence activity
      and for recognition by Pto. An amino acid substitution in AvrPtoB, F173A,
      abolishes these activities. To investigate the mechanisms of AvrPtoB virulence,
      we screened for tomato proteins that interact with AvrPtoB and identified Bti9, a
      LysM receptor-like kinase. Bti9 has the highest amino acid similarity to
      Arabidopsis CERK1 among the tomato LysM receptor-like kinases (RLKs) and belongs
      to a clade containing three other tomato proteins, SlLyk11, SlLyk12, and SlLyk13,
      all of which interact with AvrPtoB. The F173A substitution disrupts the
      interaction of AvrPtoB with Bti9 and SlLyk13, suggesting that these LysM-RLKs are
      its virulence targets. Two independent tomato lines with RNAi-mediated reduced
      expression of Bti9 and SlLyk13 were more susceptible to P. syringae. Bti9 kinase
      activity was inhibited in vitro by the N-terminal domain of AvrPtoB in an F173
      dependent manner. These results indicate Bti9 and/or SlLyk13 play a role in plant
      immunity and the N-terminal domain of AvrPtoB may have evolved to interfere with
      their kinase activity. Finally, we found that Bti9 and Pto interact with AvrPtoB
      in a structurally similar although not identical fashion, suggesting that Pto may
      have evolved as a molecular mimic of LysM-RLK kinase domains.

PMID- 21880080
TI  - Laxative management in ambulatory cancer patients on opioid therapy: a
      prospective, open-label investigation of polyethylene glycol, sodium picosulphate
      and lactulose.
AB  - Constipation and the laxatives polyethylene glycol (PEG), sodium picosulphate
      (SPS) and lactulose (L) were investigated in outpatients with cancer and on
      opioid therapy. Randomly selected patients were enrolled in a prospective,
      controlled, open-label trial. Endpoints were number of patients taking laxatives
      >28 days, number of patients with a stool-free interval >72 h (sfi72), dosage,
      numerical rating scale (NRS) for constipation, and European Organization for
      Research and Treatment of Cancer (EORTC) Quality of Life (QoL) questionnaire
      scores. The 348 patients had comparable demographic and medical data. In this
      ambulatory population, mobility scores remained unaffected. Constipation
      incidence was 5.7%, with sfi72 42, mean NRS 2.3557 and mean QoL 2.1. A total of
      53.2% discontinued their laxative medication. Laxative use correlated with higher
      opioid usage (morphine-equivalent mg/day: no laxative 98.2, SPS 128.2, PEG 139.9,
      L 154.5). PEG was the most frequently prescribed laxative (PEG 27.3%, SPS 10.3%,
      L 9.2%). PEG (sfi72 12.6%, NRS 2.2, QoL 2.1) and SPS (sfi72 11.1%, NRS 2.7, QoL
      2.2) proved more effective than L (sfi72 15.5%, NRS 3.8, QoL 2.5). In spite of
      opioid therapy, the incidence of constipation was low in these ambulatory cancer
      pain patients at an early disease stage. For prevention of constipation, PEG or
      SPS is recommended instead of L.

PMID- 21880081
TI  - Candidate mechanisms underlying effects of contractile activity on muscle
      morphology and energetics in cancer cachexia.
AB  - Skeletal muscle wasting is a prominent pathophysiological feature of cancer
      cachexia. Recent evidence suggests the manifestation of mitochondrial dysfunction
      along with a diminished oxidative capacity. These abnormalities have been
      concurrently observed with impaired muscle force production and the accelerated
      onset of fatigue in both tumour-bearing animals and cancer patients exhibiting
      wasting. To address the burden imposed by cachexia, nutritional and
      pharmacological interventions have been investigated extensively; in contrast,
      contractile activity-based countermeasures (i.e. exercise training) have been
      less frequently explored. Although limited, several preclinical studies that
      implemented contractile activity have reported favourable outcomes such as the
      retention of muscle mass and the restoration of energetic homeostasis. Even fewer
      investigations have examined the mechanisms accounting for these protective
      effects. An experimental approach addressing contractile activity-dependent
      expression of muscle mass and energy metabolism regulators may yield information
      that provides mechanistic support for exercise countermeasures. In this review,
      we present several candidate mechanisms underlying the protective effects of
      contractile activity as support for exercise countermeasure strategies. Given the
      limited quantity of data in this area, insights will be derived from studies on
      contractile activity-dependent modulation of common cellular and molecular events
      regulating muscle morphology and energetics during other muscle wasting
      conditions (e.g. sarcopenia).

PMID- 21880082
TI  - Biogeography of avian blood parasites (Leucocytozoon spp.) in two resident hosts
      across Europe: phylogeographic structuring or the abundance-occupancy
      relationship?
AB  - Relationships between hosts and parasites represent complex co-evolving systems
      that can vary both temporally and spatially. This variation may result in
      different phylogeographic outcomes, ranging from highly geographically structured
      parasite populations comprised of specialist lineages that are locally abundant
      but have restricted global occupancy to geographically unstructured parasite
      populations consisting of widespread parasites. Here, we present results from a
      large biogeographic study of the Leucocytozoon blood parasites of two nonmigrant
      bird species, conducted at nine sites across Europe. The aim was to determine
      whether the parasite lineages of the two hosts were phylogeographically
      structured across Europe. Employing molecular methods, we found a large diversity
      of parasites, and although overall prevalence varied greatly, the parasites were
      not genetically structured. Several measures of local parasite abundance were
      associated with the number of sites that the lineage occurred in, which is
      consistent with the macroecological phenomenon of the abundance-occupancy
      relationship. Taken together, our results show that parasite dispersal is
      somewhat uncoupled to that of the host in this system: we suggest that broad host
      and/or vector preference may play an important role in determining the
      distribution of these parasites and in affecting host-parasite coevolution in
      this system.

PMID- 21880083
TI  - Genetic diversity of the imperilled bath sponge Spongia officinalis Linnaeus,
      1759 across the Mediterranean Sea: patterns of population differentiation and
      implications for taxonomy and conservation.
AB  - The Mediterranean bath sponge Spongia officinalis is an iconic species with high
      socio-economic value and precarious future owing to unregulated harvesting,
      mortality incidents and lack of established knowledge regarding its ecology. This
      study aims to assess genetic diversity and population structure of the species at
      different geographical scales throughout its distribution. For this purpose, 11
      locations in the Eastern Mediterranean (Aegean Sea), Western Mediterranean
      (Provence coast) and the Strait of Gibraltar were sampled; specimens were
      analysed using partial mitochondrial cytochrome oxidase subunit I (COI)
      sequences, along with a set of eight microsatellite loci. According to our
      results (i) no genetic differentiation exists among the acknowledged
      Mediterranean morphotypes, and hence, S. officinalis can be viewed as a single,
      morphologically variable species; (ii) a notable divergence was recorded in the
      Gibraltar region, indicating the possible existence of a cryptic species; (iii)
      restriction to gene flow was evidenced between the Aegean Sea and Provence giving
      two well-defined regional clusters, thus suggesting the existence of a
      phylogeographic break between the two systems; (iv) low levels of genetic
      structure, not correlated to geographical distance, were observed inside
      geographical sectors, implying mechanisms (natural or anthropogenic) that enhance
      dispersal and gene flow have promoted population connectivity; (v) the genetic
      diversity of S. officinalis is maintained high in most studied locations despite
      pressure from harvesting and the influence of devastating epidemics. These
      findings provide a basis towards the effective conservation and management of the
      species.

PMID- 21880085
TI  - Combining chloroplast and nuclear microsatellites to investigate origin and
      dispersal of New World sweet potato landraces.
AB  - We analysed a representative collection of New World sweet potato landraces (329
      accessions from Mexico to Peru) with both chloroplast and nuclear microsatellite
      markers. Both kinds of markers supported the existence of two geographically
      restricted genepools, corresponding to accessions from the north-western part of
      South America and accessions from the Caribbean and Central America region. Our
      conservative cpSSRs markers revealed that the divergence between the two
      haplotype groups is associated with numerous mutation events concerning various
      markers, supporting the idea that this divergence may be ancient, predating
      domestication. For both kinds of markers, we found no significant difference in
      diversity between the two genepools and detected region-specific alleles in both
      groups. Previous studies have favoured the hypothesis of a single domestication
      of this crop. Our analysis suggests at least two independent domestications, in
      Central/Caribbean America and in the north-western part of South America. Sweet
      potato was then dispersed from these centres throughout tropical America.
      Comparison of nuclear and chloroplast data suggests that exchanges of clones and
      sexual reproduction were both important processes in landrace diversification in
      this clonally propagated crop. Our analysis provides useful tools for
      rationalizing the conservation and use of sweet potato germplasm collections.

PMID- 21880084
TI  - Genome-wide association analysis of clinical vs. nonclinical origin provides
      insights into Saccharomyces cerevisiae pathogenesis.
AB  - Because domesticated Saccharomyces cerevisiae strains have been used to produce
      fermented food and beverages for centuries without apparent health implications,
      S. cerevisiae has always been considered a Generally Recognized As Safe (GRAS)
      microorganism. However, the number of reported mucosal and systemic S. cerevisiae
      infections in the human population has increased and fatal infections have
      occurred even in relatively healthy individuals. In order to gain insight into
      the pathogenesis of S. cerevisiae and improve our understanding of the emergence
      of fungal pathogens, we performed a population-based genome-wide environmental
      association analysis of clinical vs. nonclinical origin in S. cerevisiae. Using
      tiling array-based, high-density genotypes of 44 clinical and 44 nonclinical S.
      cerevisiae strains from diverse geographical origins and source substrates, we
      identified several genetic loci associated with clinical background in S.
      cerevisiae. Associated polymorphisms within the coding sequences of VRP1, KIC1,
      SBE22 and PDR5, and the 5' upstream region of YGR146C indicate the importance of
      pseudohyphal formation, robust cell wall maintenance and cellular detoxification
      for S. cerevisiae pathogenesis, and constitute good candidates for follow-up
      verification of virulence and virulence-related factors underlying the
      pathogenicity of S. cerevisiae.

PMID- 21880086
TI  - Elephant behaviour and conservation: social relationships, the effects of
      poaching, and genetic tools for management.
AB  - Genetic tools are increasingly valuable for understanding the behaviour,
      evolution, and conservation of social species. In African elephants, for
      instance, genetic data provide basic information on the population genetic causes
      and consequences of social behaviour, and how human activities alter elephants'
      social and genetic structures. As such, African elephants provide a useful case
      study to understand the relationships between social behaviour and population
      genetic structure in a conservation framework. Here, we review three areas where
      genetic methods have made important contributions to elephant behavioural ecology
      and conservation: (1) understanding kin-based relationships in females and the
      effects of poaching on the adaptive value of elephant relationships, (2)
      understanding patterns of paternity in elephants and how poaching can alter these
      patterns, and (3) conservation genetic tools to census elusive populations, track
      ivory, and understand the behavioural ecology of crop-raiding. By comparing
      studies from populations that have experienced a range of poaching intensities,
      we find that human activities have a large effect on elephant behaviour and
      genetic structure. Poaching disrupts kin-based association patterns, decreases
      the quality of elephant social relationships, and increases male reproductive
      skew, with important consequences for population health and the maintenance of
      genetic diversity. In addition, we find that genetic tools to census populations
      or gather forensic information are almost always more accurate than non-genetic
      alternatives. These results contribute to a growing understanding of poaching on
      animal behaviour, and how genetic tools can be used to understand and conserve
      social species.

PMID- 21880087
TI  - The evolution of social discounting in hierarchically clustered populations.
AB  - The expression of a social behaviour may affect the fitness of actors and
      recipients living in the present and in the future of the population. When there
      is a risk that a future reward will not be experienced in such a context, the
      value of that reward should be discounted; but by how much? Here, we evaluate
      social discount rates for delayed fitness rewards to group of recipients living
      at different positions in both space and time than the actor in a hierarchically
      clustered population. This is a population where individuals are grouped into
      families, families into villages, villages into clans, and so on, possibly ad
      infinitum. The group-wide fitness effects are assumed to either increase or
      decrease the fecundity or the survival of recipients and can be arbitrarily
      extended in space and time. We find that actions changing the survival of
      individuals living in the future are generally more strongly discounted than
      fecundity-changing actions for all future times and that the value of future
      rewards increases as individuals live longer. We also find that delayed fitness
      effects may not only be discounted by a constant factor per unit delay
      (exponential discounting), but that, as soon as there is localized dispersal in a
      population, discounting per unit delay is likely to fall rapidly for small delays
      and then slowly for longer delays (hyperbolic discounting). As dispersal tends to
      be localized in natural populations, our results suggest that evolution is likely
      to favour individuals that express present-biased behaviours and that may be time
      inconsistent with respect to their group-wide effects.

PMID- 21880088
TI  - Society, demography and genetic structure in the spotted hyena.
AB  - Spotted hyenas (Crocuta crocuta) are large mammalian carnivores, but their
      societies, called 'clans', resemble those of such cercopithecine primates as
      baboons and macaques with respect to their size, hierarchical structure, and
      frequency of social interaction among both kin and unrelated group-mates.
      However, in contrast to cercopithecine primates, spotted hyenas regularly hunt
      antelope and compete with group-mates for access to kills, which are extremely
      rich food sources, but also rare and ephemeral. This unique occurrence of baboon
      like sociality among top-level predators has favoured the evolution of many
      unusual traits in this species. We briefly review the relevant socio-ecology of
      spotted hyenas, document great demographic variation but little variation in
      social structure across the species' range, and describe the long-term fitness
      consequences of rank-related variation in resource access among clan-mates. We
      then summarize patterns of genetic relatedness within and between clans,
      including some from a population that had recently gone through a population
      bottleneck, and consider the roles of sexually dimorphic dispersal and female
      mate choice in the generation of these patterns. Finally, we apply social network
      theory under varying regimes of resource availability to analyse the effects of
      kinship on the stability of social relationships among members of one large hyena
      clan in Kenya. Although social bonds among both kin and non-kin are weakest when
      resource competition is most intense, hyenas sustain strong social relationships
      with kin year-round, despite constraints imposed by resource limitation. Our
      analyses suggest that selection might act on both individuals and matrilineal kin
      groups within clans containing multiple matrilines.

PMID- 21880089
TI  - Spatial but not temporal co-divergence of a virus and its mammalian host.
AB  - Co-divergence between host and parasites suggests that evolutionary processes act
      across similar spatial and temporal scales. Although there has been considerable
      work on the extent and correlates of co-divergence of RNA viruses and their
      mammalian hosts, relatively little is known about the extent to which virus
      evolution is determined by the phylogeographic history of host species. To test
      hypotheses related to co-divergence across a variety of spatial and temporal
      scales, we explored phylogenetic signatures in Andes virus (ANDV) sampled from
      Chile and its host rodent, Oligoryzomys longicaudatus. ANDV showed strong spatial
      subdivision, a phylogeographic pattern also recovered in the host using both
      spatial and genealogical approaches, and despite incomplete lineage sorting.
      Lineage structure in the virus seemed to be a response to current population
      dynamics in the host at the spatial scale of ecoregions. However, finer scale
      analyses revealed contrasting patterns of genetic structure across a latitudinal
      gradient. As predicted by their higher substitution rates, ANDV showed greater
      genealogical resolution than the rodent, with topological congruence influenced
      by the degree of lineage sorting within the host. However, despite these major
      differences in evolutionary dynamics, the geographic structure of host and virus
      converged across large spatial scales.

PMID- 21880090
TI  - Patterns of interventions and the effect of coalitions and sociality on male
      fitness.
AB  - In group living animals, especially among primates, there is consistent evidence
      that high-ranking males gain a higher reproductive output than low-ranking males.
      Primate studies have shown that male coalitions and sociality can impact male
      fitness; however, it remains unclear whether males could potentially increase
      their fitness by preferentially supporting and socializing with females. Here we
      investigate patterns of male interventions and the effect of coalitions and
      sociality on male fitness in rhesus macaques (Macaca mulatta) with particular
      focus on male-female interactions. We combined behavioural observations collected
      on Cayo Santiago with genetic data analysed for male reproductive output and
      relatedness. Our results revealed that the ten top-ranking males provided the
      majority of all male support observed. In contrast to other primates, male rhesus
      macaques mainly formed all-down coalitions suggesting that coalitions are less
      likely used to enhance male dominance. Males supporting females during and before
      their likely conception were not more likely to fertilize those females. We also
      found no evidence that males preferably support their offspring or other close
      kin. Interestingly, the most important predictor of male support was sociality,
      since opponents sharing a higher sociality index with a given male were more
      likely to be supported. Furthermore, a high sociality index of a given male
      female dyad resulted in a higher probability of paternity. Overall, our results
      strengthen the evidence that sociality affects fitness in male primates, but also
      suggest that in species in which males queue for dominance, it is less likely
      that males derive fitness benefits from coalitions.

PMID- 21880091
TI  - Female reproductive competition in Eulemur rufifrons: eviction and reproductive
      restraint in a plurally breeding Malagasy primate.
AB  - In mammals with female philopatry, co-resident females inevitably compete with
      each other for resources or reproductive opportunities, thereby reducing the kin
      selected benefits of altruism towards relatives. These counteracting forces of
      cooperation and competition among kin should be particularly pronounced in
      plurally breeding species with limited alternative breeding opportunities outside
      the natal group. However, little is still known about the costs of reproductive
      competition on females' fitness and the victims' potential counter-strategies.
      Here we summarize long-term behavioural, demographic and genetic data collected
      on a plurally breeding primate from Madagascar to illuminate mechanisms and
      effects of female reproductive competition, focusing on forcible eviction and
      potential reproductive restraint. The main results of our study indicate that
      females in groups of redfronted lemurs (Eulemur rufifrons) above a critical size
      suffer from competition from their close relatives: females in larger groups face
      an increased probability of not giving birth as well as a higher probability of
      being evicted, especially during the annual mating and birth seasons. Eviction is
      not predicted by the number of adult females, the number of close female
      relatives, female age or inter-annual variation in rainfall but only by total
      group size. Thus, eviction in this species is clearly linked with reproductive
      competition, it cannot be forestalled by reproductive restraint or having many
      relatives in the group, and it occurs in the absence of a clear dominance
      hierarchy. Our study therefore also underscores the notion that potential
      inclusive fitness benefits from living with relatives may have been generally
      over-rated and should not be taken for granted.

PMID- 21880092
TI  - A multi-gene approach reveals a complex evolutionary history in the Cyanistes
      species group.
AB  - Quaternary climatic oscillations have been considered decisive in shaping much of
      the phylogeographic structure around the Mediterranean Basin. Within this
      paradigm, peripheral islands are usually considered as the endpoints of the
      colonization processes. Here, we use nuclear and mitochondrial markers to
      investigate the phylogeography of the blue tit complex (blue tit Cyanistes
      caeruleus, Canary blue tit C. teneriffae and azure tit C. cyanus), and assess the
      role of the Canary Islands for the geographic structuring of genetic variation.
      The Canary blue tit exhibits strong genetic differentiation within the Canary
      Islands and, in combination with other related continental species, provides an
      ideal model in which to examine recent differentiation within a closely related
      group of continental and oceanic island avian species. We analysed DNA sequences
      from 51 breeding populations and more than 400 individuals in the blue tit
      complex. Discrepancies in the nuclear and mitochondrial gene trees provided
      evidence of a complex evolutionary process around the Mediterranean Basin.
      Coalescent analyses revealed gene flow between C. caeruleus and C. teneriffae
      suggesting a dynamic process with multiple phases of colonization and geographic
      overlapping ranges. Microsatellite data indicated strong genetic differentiation
      among the Canary Islands and between the Canary archipelago and the close
      continental areas, indicating limited contemporary gene flow. Diversification of
      the blue tit complex is estimated to have started during the early Pliocene (~ 5
      Ma), coincident with the end of Messinian salinity crisis. Phylogenetic analyses
      indicated that the North African blue tit is derived from the Canary blue tits, a
      pattern is avian 'back colonization' that contrasts with more traditionally held
      views of islands being sinks rather than sources.

PMID- 21880093
TI  - Shear bond strength of resin cement bonded to alumina ceramic after treatment by
      aluminum oxide sandblasting or silica coating.
AB  - PURPOSE: To evaluate the shear bond strength and bond durability between a dual
      cured resin cement (RC) and a high alumina ceramic (In-Ceram Alumina), subjected
      to two surface treatments. MATERIALS AND METHODS: Forty disc-shaped specimens
      (sp) (4-mm diameter, 5-mm thick) were fabricated from In-Ceram Alumina and
      divided into two groups (n = 20) in accordance with surface treatment: (1)
      sandblasting by aluminum oxide particles (50 MUm Al(2) O(3) ) (SB) and (2) silica
      coating (30 MUm SiO(x) ) using the CoJet system (SC). After the 40 sp were bonded
      to the dual-cured RC, they were stored in distilled water at 37 degrees C for 24
      hours. After this period, the sp from each group were divided into two conditions
      of storage (n = 10): (a) 24 h-shear bond test 24 hours after cementation; (b)
      Aging-thermocycling (TC) (12,000 times, 5 to 55 degrees C) and water storage (150
      days). The shear test was performed in a universal test machine (1 mm/min).
      RESULTS: ANOVA and Tukey (5%) tests noted no statistically significant difference
      in the bond strength values between the two surface treatments (p = 0.7897). The
      bond strengths (MPa) for both surface treatments reduced significantly after
      aging (SB-24: 8.2 +/- 4.6; SB-Aging: 3.7 +/- 2.5; SC-24: 8.6 +/- 2.2; SC-Aging:
      3.5 +/- 3.1). CONCLUSION: Surface conditioning using airborne particle abrasion
      with either 50 MUm alumina or 30 MUm silica particles exhibited similar bond
      strength values and decreased after long-term TC and water storage for both
      methods.

PMID- 21880094
TI  - Effect of chemical disinfection and accelerated aging on color stability of
      maxillofacial silicone with opacifiers.
AB  - PURPOSE: The purpose of this study was to evaluate the color stability of MDX4
      4210 maxillofacial elastomer with opacifier addition submitted to chemical
      disinfection and accelerated aging. MATERIALS AND METHODS: Ninety specimens were
      obtained from Silastic MDX4-4210 silicone. The specimens were divided into three
      groups (n = 30): Group I: colorless, Group II: barium sulfate opacifier, Group
      III: titanium dioxide opacifier. Specimens of each group (n = 10) were
      disinfected with effervescent tablets, neutral soap, or 4% chlorhexidine
      gluconate. Disinfection was conducted three times a week for 2 months. Afterward,
      the specimens were submitted to different periods of accelerated aging. Color
      evaluation was carried out after 60 days (disinfection period) and after 252,
      504, and 1008 hours of accelerated aging, using a reflection spectrophotometer.
      Color alterations were calculated by the CIE L*a*b* system. Data were analyzed by
      three-way ANOVA and Tukey test (alpha= 0.05). RESULTS: Group II exhibited the
      lowest color change, whereas Group III the highest (p < 0.05), regardless of the
      chemical disinfection and accelerated aging periods. CONCLUSION: Opacifier
      addition, chemical disinfection, and accelerated aging procedures affected the
      color stability of the maxillofacial silicone.

PMID- 21880095
TI  - In vitro analysis of post-fatigue reverse-torque values at the dental
      abutment/implant interface for a unitarian abutment design.
AB  - PURPOSE: This study analyzed baseline and post-fatigue reverse-torque values
      (RTVs) for a specific brand control abutment relative to a third party compatible
      abutment. The purpose of this study was to compare the abutments' fatigue
      resistance to simulated function, using RTVs as an indication of residual preload
      at the implant/abutment interface. MATERIALS AND METHODS: Forty Straumann tissue
      level implants were mounted in resin and divided into four groups (n = 10). Forty
      abutments were seated, 20 control and 20 third-party abutments, according to
      manufacturer guidelines. Ten abutments from each manufacturer were evaluated for
      RTV without fatigue loading, using a calibrated digital torque gauge to provide a
      baseline RTVs. Fatigue loading was carried out on the remaining ten specimens
      from each manufacturer according to ISO 14801 guidelines. A moving-magnet linear
      motor was used to load one specimen per sequence, alternating from 10 to 200 N at
      15 Hz for 5*10(6) cycles. RTV was recorded post-fatigue loading. The results were
      subjected to two-sample t-testing and two-way ANOVA. Scanning electron
      microphotography was carried out on three specimens from both manufacturers at
      baseline and post-fatigue cycling to visualize thread geometry and the
      abutment/implant interface. RESULTS: The data indicated that mean post-fatigue
      RTV observed for the control group was significantly higher than the third-party
      group (RTV 42.65 +/- 6.70 N vs. 36.25 +/- 2.63 N, p= 0.0161). Visual differences
      at the macro/microscopic level were also apparent for thread geometry, with third
      party abutments demonstrating considerably greater variation in geometrical
      architecture than control specimens. CONCLUSIONS: Within the limitations of this
      in vitro model, the effect of component manufacturer resulted in a significantly
      higher RTV in the control group (two-way ANOVA, p= 0.0032) indicating greater
      residual preload; however, there was no significant decrease in post-fatigue RTV
      for either manufacturer compared to baseline.

PMID- 21880096
TI  - A 10-year survey of US deans: trends, challenges, and mentoring in
      prosthodontics. Part 2.
AB  - PURPOSE: Part 2 of this survey reports on the 2009 survey findings distributed to
      the deans of US dental schools. A national, electronic survey of 58 dental school
      deans was distributed by e-mail to evaluate an interest in specialty training, an
      interest in specialty training in prosthodontics, faculty shortage issues,
      predoctoral curriculum in prosthodontics, ideology regarding dental specialties,
      and the administrative position of prosthodontics within the schools. MATERIALS
      AND METHODS: The survey data were transferred to an online spreadsheet program
      for statistical analysis (Key Survey, Inc. http://www.keysurvey.com, Braintree,
      MA). The opinions of dental school deans were viewed as legitimate indicators of
      change within predoctoral and postdoctoral prosthodontic education. Statistical
      analysis was carried out using Statistica Version 9.1 (Statsoft, Tulsa, OK).
      RESULTS: Of the 58 deans, 42 deans responded, for a 72.4% response rate. Twenty
      three deans reported an increase in the number of students seeking specialty
      training after dental school. Only three deans reported a decrease in those
      seeking specialty training. In the 2009 survey, 45% the deans responded that
      there was an increased interest in prosthodontics. One or more open faculty
      positions in prosthodontics existed at 24 (59%) of the dental schools, and 30
      (71%) offered at least one incentive or a variety of incentives to recruit
      faculty. The 2009 respondents to the deans' survey revealed predoctoral student
      exposure to prosthodontists was high, and exposure to advanced education in
      prosthodontics students was low. A survey of internal school programs that might
      have an impact on an increased interest in prosthodontics revealed the presence
      of a predoctoral mentoring program for prosthodontics in 36 (88%) of the
      institutions. The clinical curriculum included treatment of a variety of cases
      including complex cases as defined by a diagnostic classification system. The
      2009 survey respondents reported an increase in the number of schools where
      prosthodontics is a separate entity or department. CONCLUSION: Deans reported an
      increased interest in prosthodontics in the 2009 survey. Open faculty positions
      in prosthodontics existed in the majority of dental schools, and most schools
      offered incentives to recruit faculty. The survey of deans found a very high
      level of exposure of dental students to full-time prosthodontists and a very low
      exposure level to students enrolled in advanced education in prosthodontics. The
      establishment of mentoring programs in prosthodontics was reported by most deans,
      and the predoctoral curriculum included treating complex cases. Most deans stated
      that dual-specialty training in prosthodontics and periodontics would be
      beneficial. The 2009 survey reported an increase in the number of departments of
      prosthodontics in US schools.

PMID- 21880097
TI  - Intrathecal infusion of bupivacaine and clonidine provides effective analgesia in
      a terminally ill child.
AB  - The intrathecal infusion of drugs to provide analgesia for terminally ill
      children with refractory pain is a rarely utilized but very effective technique.
      A number of pharmacological agents, most commonly opioids and local anesthetics,
      have been administered intrathecally for this purpose. However, tachyphylaxis and
      neuraxial opioid-related side effects can limit their utility. The alpha-2
      agonist clonidine is commonly used to augment local anesthetic techniques for
      postsurgical pain in children and for the management of refractory cancer pain in
      adults, but there is only a single report of the use of clonidine intrathecally
      in a terminally ill child. We present the case of the youngest reported child to
      have received intrathecal analgesia for terminal care: a 3-year-old boy with
      advanced pelvic rhabdomyosarcoma, whose refractory pain was managed effectively
      with an intrathecal infusion of bupivacaine and preservative-free clonidine.

PMID- 21880098
TI  - Active surveillance of antibiotic resistance prevalence in urinary tract and skin
      infections in the outpatient setting.
AB  - The aim of the study was to evaluate the need for active surveillance of
      antibiotic resistance in ambulatory infections. We measured the prevalence of
      antibiotic resistance in urinary tract infections (UTIs) (n = 1018) and skin
      infections (n = 213) diagnosed in outpatients between September 2008 and February
      2009 in the Canton of Bern, Switzerland. Samples were stratified into 'solicited'
      (diagnostic work-up for study purpose only) and 'routine' (diagnostic work-up as
      part of standard care). Susceptibility patterns were compared for 463 Escherichia
      coli isolates from UTIs (231 solicited; 232 routine) and 87 Staphylococcus aureus
      isolates from skin infections (35 solicited; 52 routine). Overall, E. coli showed
      higher susceptibility to ampicillin, amoxicillin-clavulanic acid and norfloxacin
      in solicited than in routine samples. Among 15-45-year-old patients,
      susceptibility rates were comparable between solicited and routine samples for
      all antibiotics except for amoxicillin-clavulanic acid. However, among patients
      >45 years old, isolates from routine samples showed lower susceptibility to all
      beta-lactams tested and quinolones than those from solicited samples. Extended
      spectrum beta-lactamase (ESBL)-producing E. coli isolates were rare (solicited,
      0.4%; routine, 1.7%; p 0.4). Susceptibility patterns of S. aureus were comparable
      between solicited and routine samples. Therefore, in the outpatient setting,
      susceptibility rates for E. coli isolates differ by indication for urinary
      culture and age. Surveillance based on samples taken during standard care may
      underestimate susceptibility rates for uncomplicated infections, especially among
      the elderly. Reports of resistance data should include age stratification.

PMID- 21880099
TI  - Non-neuroinvasive West Nile virus infections during the outbreak in Greece.
AB  - A major outbreak of West Nile virus (WNV) infections took place in 2010 in
      Greece. Apart from the neuroinvasive cases, many additional cases without
      involvement of the nervous system were observed, characterized by high fever,
      myalgia, rash, leukopenia, and long-lasting recovery. West Nile non-neuroinvasive
      disease is a distinct clinical syndrome, and is not always mild.

PMID- 21880100
TI  - Inner nuclear membrane protein Ima1 is dispensable for intranuclear positioning
      of centromeres.
AB  - Inner nuclear membrane (INM) proteins play a role in spatial organization of
      chromosomes within the nucleus. In the fission yeast Schizosaccharomyces pombe,
      Sad1, an INM protein of the conserved SUN-domain family, plays an active role in
      moving chromosomes along the nuclear membranes during meiotic prophase. Ima1 is
      another conserved INM protein recently identified. A previous study claimed that
      Ima1 is essential for mitotic cell growth, linking centromeric heterochromatin to
      the spindle-pole body. However, we obtained results contradictory to the
      previously proposed role for Ima1: Ima1 was dispensable for mitotic cell growth
      or centromere positioning. This discrepancy was attributed to incorrect ima1
      deletion mutants used in the previous study. Our results show that Ima1
      collaborates with two other conserved INM proteins of the LEM-domain family that
      are homologous to human Man1 and Lem2. Loss of any one of three INM proteins has
      no effect on mitotic cell growth; however, loss of all these proteins causes
      severe defects in mitotic cell growth and nuclear membrane morphology.
      Considering that all three INM proteins interact with Sad1, these results suggest
      that Ima1, Lem2 and Man1 play at least partially redundant roles for nuclear
      membrane organization.

PMID- 21880102
TI  - Co-metabolic conversion of toluene in anaerobic n-alkane-degrading bacteria.
AB  - Diverse microorganisms have been described to degrade petroleum hydrocarbons
      anaerobically. Strains able to utilize n-alkanes do not grow with aromatic
      hydrocarbons, whereas strains able to utilize aromatic hydrocarbons do not grow
      with n-alkanes. To investigate this specificity in more detail, three anaerobic n
      alkane degraders (two denitrifying, one sulfate-reducing) and eight anaerobic
      alkylbenzene degraders (five denitrifying, three sulfate-reducing) were incubated
      with mixtures of n-alkanes and toluene. Whereas the toluene degradationers formed
      only the characteristic toluene-derived benzylsuccinate and benzoate, but no n
      alkane-derived metabolites, the n-alkane degraders formed toluene-derived
      benzylsuccinate, 4-phenylbutanoate, phenylacetate and benzoate besides the
      regular n-alkane-derived (1-methylalkyl)succinates and methyl-branched
      alkanoates. The co-metabolic conversion of toluene by anaerobic n-alkane
      degraders to the level of benzoate obviously follows the anaerobic n-alkane
      degradation pathway with C-skeleton rearrangement and decarboxylation rather than
      the beta-oxidation pathway of anaerobic toluene metabolism. Hence, petroleum
      derived aromatic metabolites detectable in anoxic environments may not be
      exclusively formed by genuine alkylbenzene degraders. In addition, the hitherto
      largely unexplored fate of fumarate hydrogen during the activation reactions was
      examined with (2,3-(2) H(2) )fumarate as co-substrate. Deuterium was completely
      exchanged with hydrogen at the substituted carbon atom (C-2) of the succinate
      adducts of n-alkanes, whereas it is retained in toluene-derived benzylsuccinate,
      regardless of the type of enzyme catalysing the fumarate addition reaction.

PMID- 21880103
TI  - Single-stage segmental urethral replacement using combined ventral onlay
      fasciocutaneous flap with dorsal onlay buccal grafting for long segment
      strictures.
AB  - Study Type--Therapy (case series). Level of Evidence 4. What's known on the
      subject? And what does the study add? Single-stage urethral segment replacement
      has historically poor outcomes and two-stage repairs are now more common. We
      present a novel approach to the single-stage repair with initial outcomes similar
      to two-stage repairs. OBJECTIVE: * To present our experience with repairing long
      segment urethral strictures in a single-stage using a combined tissue-transfer
      technique. PATIENTS AND METHODS: * In all, 14 men underwent urethroplasty where a
      segment of urethra was completely replaced using a dorsal onlay buccal mucosa
      graft and a ventral onlay fasciocutaneous flap in a single stage. * Primary
      success was defined as an open urethra at >6 months follow-up with no need for
      additional surgical intervention. * Secondary success was defined as the need for
      a single postoperative endoscopic procedure before stricture stabilization. *
      Failure was the need for multiple endoscopic procedures, repeat urethroplasty,
      urinary diversion or intermittent dilatation. RESULTS: * The mean (SD) stricture
      length was 9.75 (4.6) cm. The mean (SD) neourethral length was 5.4 (2.7) cm.
      Stricture location was penile/bulbar in 12 men, and bulbar alone in two. Primary
      success was achieved in nine of the 14 men at a median (range) follow-up of 2.5
      (0.5-9.43) years. * The mean (SD) time to recurrence in the five initial failures
      was 340 (376) days. * Secondary success was achieved in two men after a single
      endoscopic procedure for an overall success in 11 of 14 men. * Patients that
      recurred had longer strictures (12.8 vs 8.7 cm, P= 0.04) than initial successes,
      but neourethral lengths were similar (6.2 vs 5.1 cm, P= 0.5). * In all, three of
      the 14 men failed, two of whom required a repeat urethroplasty. CONCLUSIONS: *
      Our initial outcomes were favourable using the combined tissue-transfer technique
      for segmental urethral replacement with initial and secondary success rates
      similar to those reported for two-stage repairs. * This technique is not suitable
      for all patients as it requires healthy penile skin, but appears to be effective
      when a single-stage repair is desirable.

PMID- 21880104
TI  - Evolution of the clinical presentation of men undergoing radical prostatectomy
      for high-risk prostate cancer.
AB  - OBJECTIVE: To investigate the outcomes and potential effect of improved
      longitudinal screening in men presenting with high-risk (advanced clinical stage
      [>T2b], Gleason score 8-10 or prostate-specific antigen [PSA] level >20 ng/mL)
      prostate cancer (PC). PATIENTS AND METHODS: The Institutional Review Board
      approved, Institutional Radical Prostatectomy Database (1992-2010) was queried
      for men with high-risk PC based on D'Amico criteria. Year of surgery was divided
      into two cohorts: the Early PSA Era (EPE, 1992-2000) and the Contemporary PSA Era
      (CPE, 2001-2010). PC features and outcomes were evaluated using appropriate
      comparative tests. RESULTS: In total, 667 men had high-risk PC in the EPE and 764
      in the CPE. In the EPE, 598 (89.7%) men presented with one high-risk feature; 173
      (29.0%) men had a Gleason score of 8-10 on biopsy. In the CPE, 717 (93.9%) men
      presented with one high-risk feature (P = 0.004) and 494 (68.9%) men had a
      Gleason score of 8-10. At 10 years, biochemical-free survival (BFS) was 44.1% and
      36.4% in the EPE and CPE, respectively (P = 0.04); metastases-free survival (MFS)
      was 77.1% and 85.1% (P = 0.6); and PC-specific survival (CSS) was 83.3% and 96.2%
      (P = 0.5). BFS, MFS and CSS were worse for men with more than one high-risk
      feature in both eras. CONCLUSIONS: Over the PSA era, an increasing percentage of
      men with high-risk PC were categorized by a biopsy Gleason score of 8-10. The
      accumulation of multiple high-risk features increases the risk of biochemical
      recurrence, the development of metastases and death from PC. BFS, MFS and CSS are
      stable over the PSA era for these men. The balance between a greater proportion
      of men having high Gleason disease and a greater proportion with small, less
      advanced tumours may explain the stability in MFS and CSS over time.

PMID- 21880105
TI  - A population-based assessment of the National Comprehensive Cancer Network
      practice guideline indications for pelvic lymph node dissection at radical
      prostatectomy.
AB  - OBJECTIVES: To examine the ability of the threshold recommended by the National
      Comprehensive Cancer Network (NCCN) in correctly predicting histologically
      confirmed lymph node invasion (LNI). The 2010 NCCN practice guidelines for
      prostate cancer recommend a pelvic lymph node dissection (PLND) at radical
      prostatectomy in all individuals with a nomogram predicted LNI risk of >=2%.
      PATIENTS AND METHODS: We assessed 20,877 patients who were treated with radical
      prostatectomy and PLND between 2004 and 2006, within the Surveillance,
      Epidemiology and End Results database. The 2% nomogram threshold, as well as
      other threshold values (range 1-10%) were tested. Finally, we externally
      validated the NCCN guideline nomogram. RESULTS: Overall, 2.5% of patients had
      LNI. The use of the 2% threshold would allow the avoidance of 23% of PLNDs, at
      the cost of missing 1.7% of patients with LNI. Conversely, the use of a 3%
      threshold would allow the avoidance of 58% of PLNDs, at the cost of missing 15%
      of patients with LNI vs 72% and 26%, respectively, for the 4% threshold. Overall,
      the accuracy of the NCCN guideline nomogram quantified according to the receiver
      operator characteristics-derived area under the curve was 82%. CONCLUSIONS: In a
      population-based sample, the NCCN guideline nomogram is highly accurate. However,
      the 2% threshold will permit the avoidance of only 23% of PLNDs, instead of the
      48% intended by the NCCN guidelines. The use of a 3% threshold may allow a lower
      rate of PLND overtreatment, although it will miss more patients with LNI.

PMID- 21880106
TI  - Species' identification and microarray-based comparative genome analysis of
      Streptomyces species isolated from potato scab lesions in Norway.
AB  - Streptomyces strains were isolated from scab lesions on potatoes collected from
      different parts of Norway. Twenty-eight plant-pathogenic strains, as tested on
      seedlings of radish and on potato, were identified on the basis of physiological
      and molecular criteria. Polymerase chain reaction (PCR) analysis, using species
      specific primers, and sequencing of the 16S rRNA gene identified 14 nonmelanin
      producing strains to S. turgidiscabies. Fourteen melanin-producing strains were
      detected with primers specific to S. scabies, but whole-genome microarray
      analysis, based on 12 766 probes designed for 8848 predicted open reading frames
      (ORFs) of S. scabies, showed that the 14 strains were different from S. scabies.
      They were subsequently identified to be S. europaeiscabiei based on the internal
      transcribed spacer (ITS) sequences of the rRNA genes. This is the first report of
      the occurrence of S. turgidiscabies and S. europaeiscabiei in Norway. The
      putative 762 genes exhibiting the highest sequence differences between strains of
      S. europaeiscabiei and S. scabies according to microarray analysis were
      concentrated in relatively few gene ontology (GO) categories, including
      'symbiosis and mutualism through parasitism', 'cell death' and 'responses to
      biotic stimulus', whereas genes related to primary metabolism appeared to be more
      conserved. Microarray data and 16S rRNA gene phylogeny showed, consistently, that
      there were two genetically distinguishable groups of S. europaeiscabiei on the
      basis of differences in 131 genes. The results provide novel information about
      the genetic variability of S. europaeiscabiei and the gene-specific variability
      between the genomes of S. europaeiscabiei and S. scabies. The usefulness of a
      custom-designed, whole-genome oligonucleotide microarray in a survey of bacterial
      plant pathogens was demonstrated.

PMID- 21880107
TI  - A combined biochemical screen and TILLING approach identifies mutations in
      Sorghum bicolor L. Moench resulting in acyanogenic forage production.
AB  - Cyanogenic glucosides are present in several crop plants and can pose a
      significant problem for human and animal consumption, because of their ability to
      release toxic hydrogen cyanide. Sorghum bicolor L. contains the cyanogenic
      glucoside dhurrin. A qualitative biochemical screen of the M2 population derived
      from EMS treatment of sorghum seeds, followed by the reverse genetic technique of
      Targeted Induced Local Lesions in Genomes (TILLING), was employed to identify
      mutants with altered hydrogen cyanide potential (HCNp). Characterization of these
      plants identified mutations affecting the function or expression of dhurrin
      biosynthesis enzymes, and the ability of plants to catabolise dhurrin. The main
      focus in this study is on acyanogenic or low cyanide releasing lines that contain
      mutations in CYP79A1, the cytochrome P450 enzyme catalysing the first committed
      step in dhurrin synthesis. Molecular modelling supports the measured effects on
      CYP79A1 activity in the mutant lines. Plants harbouring a P414L mutation in
      CYP79A1 are acyanogenic when homozygous for this mutation and are phenotypically
      normal, except for slightly slower growth at early seedling stage. Detailed
      biochemical analyses demonstrate that the enzyme is present in wild-type amounts
      but is catalytically inactive. Additional mutants capable of producing dhurrin at
      normal levels in young seedlings but with negligible leaf dhurrin levels in
      mature plants were also identified. No mutations were detected in the coding
      sequence of dhurrin biosynthetic genes in this second group of mutants, which are
      as tall or taller, and leafier than nonmutated lines. These sorghum mutants with
      reduced or negligible dhurrin content may be ideally suited for forage
      production.

PMID- 21880108
TI  - Impact of laparoscopic adjustable gastric banding on type 2 diabetes.
AB  - Bariatric surgery is becoming an accepted option for obese people with type 2
      diabetes. Our aim was to assess the impact of laparoscopic adjustable gastric
      banding (LAGB) through a systematic review of the literature. Data was sourced
      from Scopus, MEDLINE and EMBASE published from 2000 through May 2011, and five
      unpublished studies that were performed by industry for regulatory approval were
      also included. Studies were selected on the basis that they provide some detail
      of diabetes status before and after LAGB. There were 35 studies meeting the
      inclusion criteria. There was considerable heterogeneity in study design, sample
      size, length of follow-up, attrition rates and classification of diabetes status.
      Weight loss was progressive over the first 2 years with a weighted average of 47%
      excess weight loss at 2 years. Remission or improvement in diabetes varied from
      53% to 70% over different time periods. Results were broadly consistent,
      demonstrating clinically relevant improvements in diabetes outcomes with
      sustained weight loss in obese people with type 2 diabetes following LAGB
      surgery. However, there were significant shortcomings in the reviewed literature
      with few high-quality studies, inconsistent reporting of diabetes outcomes and
      high attrition rates. Long-term studies that address these limitations are
      needed.

PMID- 21880109
TI  - The effect of smoking cessation counselling in pregnant women: a meta-analysis of
      randomised controlled trials.
AB  - BACKGROUND: Pregnant smokers are often prescribed counselling as part of
      multicomponent cessation interventions. However, the isolated effect of
      counselling in this population remains unclear, and individual randomised
      controlled trials (RCTs) are inconclusive. OBJECTIVE: To conduct a meta-analysis
      of RCTs examining counselling in pregnant smokers. SEARCH STRATEGY: We searched
      the CDC Tobacco Information and Prevention, Cochrane Library, EMBASE, Medline and
      PsycINFO databases for RCTs evaluating smoking cessation counselling. SELECTION
      CRITERIA: We included RCTs conducted in pregnant women in which the effect of
      counselling could be isolated and those that reported biochemically validated
      abstinence at 6 or 12 months after the target quit date. DATA COLLECTION AND
      ANALYSIS: Overall estimates were derived using random effects meta-analysis
      models. MAIN RESULTS: Our search identified eight RCTs (n = 3290 women), all of
      which examined abstinence at 6 months. The proportion of women that remained
      abstinent at the end of follow up was modest, ranging from 4 to 24% among those
      randomised to counselling and from 2 to 21% among control women. The absolute
      difference in abstinence reached a maximum of only 4%. Summary estimates are
      inconclusive because of wide confidence intervals, albeit with little evidence to
      suggest that counselling is efficacious at promoting abstinence (odds ratio 1.08,
      95% confidence interval 0.84-1.40). There was no evidence to suggest that
      efficacy differed by counselling type. CONCLUSIONS: Available data from RCTs
      examining the isolated effect of smoking cessation counselling in pregnant women
      are limited but sufficient to rule out large treatment effects. Future RCTs
      should examine pharmacological therapies in this population.

PMID- 21880110
TI  - A novel cause for abnormal liver function tests in pregnancy and the puerperium:
      non-alcoholic fatty liver disease.
AB  - Non-alcoholic fatty liver disease (NAFLD) is the commonest liver disease in the
      western world, but has never been reported in pregnancy before. We suggest that
      NAFLD should also be considered as a cause for abnormal liver function tests
      during pregnancy. As NAFLD is driven by insulin resistance, it is biologically
      plausible that pregnancy may reveal previously subclinical disease. Obstetricians
      have a vital role in optimising maternal health during and after pregnancy and
      therefore we need to include NAFLD in the differential diagnosis for abnormal
      liver function tests and recommend lifestyle modifications that may prevent
      progression to cirrhosis and hepatocellular carcinoma.

PMID- 21880111
TI  - A systematic review of ketamine as an analgesic agent in adult burn injuries.
AB  - OBJECTIVE: To assess the current literature regarding the effectiveness and side
      effect profile of intravenous ketamine as a means of pain relief when compared
      with placebo or as an adjunct to opioid analgesia in patients exposed to burn
      injury. DESIGN: Electronic searches of MEDLINE, CINAHL, Embase, and The Cochrane
      Library databases from 1966 onward were used to identify clinical trials
      comparing ketamine with placebo in the adult burn population. OUTCOMES MEASURED:
      Effectiveness and side-effect profile of ketamine as an analgesic agent in burn
      injuries. RESULTS: Four experimental trials involving 67 patients were
      identified. Due to heterogeneity of studies, pooling of the results and meta
      analysis were not possible. Intravenous ketamine showed some efficacy as an
      analgesic for burn injuries, with a reduction in secondary hyperalgesia when
      compared with opioid analgesia alone. Combination therapy of ketamine and
      morphine resulted in the abolishment of windup pain phenomena. The side-effect
      profile did not result in the withdrawal of any participants included in the
      studies' results. CONCLUSIONS: Further well-designed randomized controlled trials
      conducted in burn-specific populations are warranted, thus enabling the
      development of a relevant evidence base to support its clinical use.

PMID- 21880112
TI  - Best evidence on B-domain deletion and the immunogenicity of recombinant factor
      VIII.

PMID- 21880113
TI  - Angiostatic kinase inhibitors to sustain photodynamic angio-occlusion.
AB  - Targeted angiostatic therapy receives major attention for the treatment of cancer
      and exudative age-related macular degeneration (AMD). Photodynamic therapy (PDT)
      has been used as an effective clinical approach for these diseases. As PDT can
      cause an angiogenic response in the treated tissue, combination of PDT with anti
      angiogenic compounds should lead to improved therapy. This study was undertaken
      to test the clinically used small molecule kinase inhibitors Nexavar(r)
      (sorafenib), Tarceva(r) (erlotinib) and Sutent(r) (sunitinib) for this purpose,
      and to compare the results to the combination of Visudyne(r)-PDT with Avastin(r)
      (bevacizumab) treatment. When topically applied to the chicken chorioallantoic
      membrane at embryo development day (EDD) 7, a clear inhibition of blood vessel
      development was observed, with sorafenib being most efficient. To investigate the
      combination with phototherapy, Visudyne(r)-PDT was first applied on EDD11 to
      close all <100 MUm vessels. Application of angiostatics after PDT resulted in a
      significant decrease in vessel regrowth in terms of reduced vessel density and
      number of branching points/mm(2) . As the 50% effective dose (ED50) for all
      compounds was approximately 10-fold lower, Sorafenib outperformed the other
      compounds. In vitro, all kinase inhibitors decreased the viability of human
      umbilical vein endothelial cells. Sunitinib convincingly inhibited the in vitro
      migration of endothelial cells. These results suggest the therapeutic potential
      of these compounds for application in combination with PDT in anti-cancer
      approaches, and possibly also in the treatment of other diseases where
      angiogenesis plays an important role.

PMID- 21880114
TI  - SNARE complex-mediated degranulation in mast cells.
AB  - Mast cell function and dysregulation is important in the development and
      progression of allergic and autoimmune disease. Identifying novel proteins
      involved in mast cell function and disease progression is the first step in the
      design of new therapeutic strategies. Soluble N-ethylmaleimide-sensitive factor
      attachment protein receptors (SNAREs) are a family of proteins demonstrated to
      mediate the transport and fusion of secretory vesicles to the membrane in mast
      cells, leading to the subsequent release of the vesicle cargo through an
      exocytotic mechanism. The functional role[s] of specific SNARE family member
      complexes in mast cell degranulation has not been fully elucidated. Here, we
      review recent and historical data on the expression, formation and localization
      of various SNARE proteins and their complexes in murine and human mast cells. We
      summarize the functional data identifying the key SNARE family members that
      appear to participate in mast cell degranulation. Furthermore, we discuss the
      utilization of RNA interference (RNAi) methods to validate SNARE function and the
      use of siRNA as a therapeutic approach to the treatment of inflammatory disease.
      These studies provide an overview of the specific SNARE proteins and complexes
      that serve as novel targets for the development of new therapies to treat
      allergic and autoimmune disease.

PMID- 21880115
TI  - Selenodiglutathione uptake by the Saccharomyces cerevisiae vacuolar ATP-binding
      cassette transporter Ycf1p.
AB  - The Saccharomyces cerevisiae vacuolar ATP-binding cassette transporter Ycf1p is
      involved in heavy metal detoxification by mediating the ATP-dependent transport
      of glutathione-metal conjugates to the vacuole. In the case of selenite toxicity,
      deletion of YCF1 was shown to confer increased resistance, rather than
      sensitivity, to selenite exposure [Pinson B, Sagot I & Daignan-Fornier B (2000)
      Mol Microbiol36, 679-687]. Here, we show that when Ycf1p is expressed from a
      multicopy plasmid, the toxicity of selenite is exacerbated. Using secretory
      vesicles isolated from a sec6-4 mutant transformed either with the plasmid
      harbouring YCF1 or the control plasmid, we establish that the glutathione
      conjugate selenodigluthatione is a high-affinity substrate of this ATP-binding
      cassette transporter and that oxidized glutathione is also efficiently
      transported. Finally, we show that the presence of Ycf1p impairs the
      glutathione/oxidized glutathione ratio of cells subjected to a selenite stress.
      Possible mechanisms by which Ycf1p-mediated vacuolar uptake of
      selenodiglutathione and oxidized glutathione enhances selenite toxicity are
      discussed.

PMID- 21880116
TI  - Structure and function of a complex sensory synapse.
AB  - Vision is the most important of the senses for humans, and the retina is the
      first stage in the processing of light signals in the visual system. In the
      retina, highly specialized light-sensing neurons, the rod and cone
      photoreceptors, convert light into neural signals. These signals are extensively
      processed and filtered in the subsequent retinal network before transmitted to
      the higher visual centres in the brain, where the perception of viewed objects
      and scenes is finally constructed. A key feature of signal processing in the
      mammalian retina is parallel processing. Visual information is segregated in
      parallel pathways already at the rod and cone photoreceptor terminals, which
      provide multiple output synapses for the faithful encoding and transfer of the
      visual signals to the post-receptoral retinal network. This review aims at
      highlighting the current knowledge about the structural and functional pre- and
      post-synaptic specializations of rod and cone photoreceptor ribbon synapses,
      which belong to the most complex chemical synapses in the central nervous system.

PMID- 21880117
TI  - Vaccines for the future: learning from human immunology.
AB  - Conventional vaccines have been extremely successful in preventing infections by
      pathogens expressing relatively conserved antigens through antibody-mediated
      effector mechanisms. Thanks to vaccination some diseases have been eradicated and
      mortality due to infectious diseases has been significantly reduced. However,
      there are still many infections that are not preventable with vaccination, which
      represent a major cause of mortality worldwide. Some of these infections are
      caused by pathogens with a high degree of antigen variability that cannot be
      controlled only by antibodies, but require a mix of humoral and cellular immune
      responses. Novel technologies for antigen discovery, expression and formulation
      allow now for the development of vaccines that can better cope with pathogen
      diversity and trigger multifunctional immune responses. In addition, the
      application of new genomic assays and systems biology approaches in human
      immunology can help to better identify vaccine correlates of protection. The
      availability of novel vaccine technologies, together with the knowledge of the
      distinct human immune responses that are required to prevent different types of
      infection, should help to rationally design effective vaccines where conventional
      approaches have failed.

PMID- 21880119
TI  - Long-term quality-of-life outcomes in children undergoing adenotonsillectomy for
      obstructive sleep apnoea: a longitudinal study.
AB  - OBJECTIVES: To assess a cohort of patients who underwent adenotonsillectomy for
      obstructive sleep apnoea, 4 years after surgery for evidence of continued and
      long-term improvement in quality of life. We also sought to compare our results
      to Child Health Questionnaire scores obtained from our previous study. We also
      compared our data with a healthy UK children population from normative data
      available. DESIGN: Longitudinal study. SETTINGS: University Hospital Tertiary
      Referral Centre. PARTICIPANTS: A 4-year follow-up study of 37 children who
      underwent adenotonsillectomy for obstructive sleep apnoea confirmed on
      polysomnography. There were 19 boys and 18 girls from our initial cohort. The
      primary caregiver completed the validated Child Health Questionnaire Parental
      Form version-28, 4 years after initial surgery. Our control group consist of 221
      healthy children aged 6-18 that were included as 'normal' controls in a study
      looking at children with juvenile arthritis. The children were defined as healthy
      by a physician and/or after declaration by the parent. MAIN OUTCOME MEASURE:
      Child Health Questionnaire Parental Form version-28 scores. RESULTS: A total of
      33 patients (89%) from our initial cohort were contacted. The mean age was 10.6
      (median, 11; range, 5-16). When compared with results obtained 3 months
      postoperatively, the mean scores were higher in five domains and were
      statistically significant in three subscales (Role Limitations P < 0.00001;
      Bodily Pain P < 0.002; and Global Health P < 0.02). There was a significant
      deterioration in Behaviour subscale (P < 0.0007) in spite of surgery. Compared
      with controls, 4-year follow-up scores were higher in five domains with the
      Global Health domain (P < 0.0004) being statistically significant. When the 4
      year follow-up scores were compared with preoperative values, these were higher
      in all 13 domains with statistically significant improvements in nine domains,
      indicating that improvements had persisted 4 years after surgery. At 4 years,
      however, the means scores in many domains remain lower when compared with
      controls. CONCLUSION: Quality-of-life data are an important measure when deciding
      on a specific clinical intervention. In the short term, quality-of-life measures
      have been shown to improve after adenotonsillectomy for obstructive sleep apnoea.
      Our study demonstrates that the benefits of surgery are still persistent and the
      children continue to improve in the long term.

PMID- 21880118
TI  - Vaccination in the elderly.
AB  - There is a general consensus that the elderly do not respond as well to
      vaccination as the young, but robust studies are few and far between. Most refer
      to influenza vaccination, but even here, adequate immunological and clinical data
      are surprisingly thin on the ground. The meta-analysis by Goodwin et al. from
      2006 is still the most comprehensive that we have. They reviewed 31 antibody
      response studies comparing influenza vaccination efficacy in groups of elderly
      and younger adults. They reported that the adjusted odds ratio (OR) of responses
      in elderly versus young adults ranged from 0.24 to 0.59 for the three influenza
      antigens used in the vaccines. They concluded that rather than the estimated 70
      90% clinical vaccine efficacy in younger adults, this figure was only 17-53% in
      the elderly, depending on which viruses were prevalent that year. They stated
      that 'this highlights the need for more immunogenic vaccine formulations for the
      elderly'. How to achieve this? There are three areas where we may consider
      alterations to increase vaccine efficacy: (i) make the vaccine more potent; (ii)
      use adjuvants to enhance immunity; and (iii) apply immune modulators or other
      interventions to alter host immunity generally. We will consider these three
      options, focusing on influenza vaccination, in this mini-review.

PMID- 21880120
TI  - Pancreatectomy for metastasis to the pancreas from colorectal cancer and
      reconstruction of superior mesenteric vein: a case report.
AB  - INTRODUCTION: Tumors of the pancreatic head can infiltrate the superior
      mesenteric vein. In such cases, the deep veins of the lower limbs can serve as
      suitable autologous conduits for superior mesenteric vein reconstruction after
      its resection. Few data exist, however, describing the technique and the
      immediate patency of such reconstruction. CASE REPORT: We present the case of a
      70-year-old Caucasian man with a metachronous metastasis of colon cancer and
      infiltration of the uncinate pancreatic process, on the anterior surface of which
      the tumor was located. En bloc resection of the tumor was performed with
      resection of the superior mesenteric vein and reconstruction. A 10 cm segment of
      the superficial femoral vein was harvested for the reconstruction. The
      superficial femoral vein segment was inter-positioned in an end-to-end fashion.
      The post-operative conduit patency was documented ultrasonographically
      immediately post-operatively and after a six-month period. The vein donor limb
      presented subtle signs of post-operative venous hypertension with edema, which
      was managed with compression stockings and led to significant improvement after
      six months. CONCLUSION: In cases of exploratory laparotomies with high clinical
      suspicion of pancreatic involvement, the potential need for vascular
      reconstruction dictates the preparation for leg vein harvest in advance. The
      superficial femoral vein provides a suitable conduit for the reconstruction of
      the superior mesenteric vein. This report supports the uncomplicated nature of
      this technique, since few data exist about this type of reconstruction.

PMID- 21880121
TI  - Vital capacity evolution in patients treated with the CMCR brace: statistical
      analysis of 90 scoliotic patients treated with the CMCR brace.
AB  - SUMMARY:  OBJECTIVE: To study the evolution of pulmonary capacity during
      orthopaedic treatment of scoliosis with the CMCR brace. BACKGROUND: Investigating
      the impact of moderate scoliosis on respiratory capacity and its evolution during
      CMCR brace treatment with mobile pads. CONTEXT: Several studies demonstrate the
      impact of scoliosis on respiratory capacity but few of them focus on the impact
      of bracing treatment. We studied the evolution of the pulmonary capacity of a
      cohort of 90 scoliotic patients. METHODS: This retrospective study included 90
      scoliotic patients treated since 1999 with a brace with mobile pads called CMCR
      (n = 90; mean age: 13 years; 10-16). These patients were diagnosed with an
      idiopathic scoliosis (mean angulation 20.6 degrees ). All patients underwent a
      radiographic and respiratory evaluation at the beginning, the middle and the end
      of treatment. RESULTS: Mean age at treatment start was 13. Before treatment, our
      patients did not have a normal pulmonary capacity: Forced Vital Capacity (FVC)
      was only 75% of the theoretical value. All curvature types (thoracic, thoraco
      lumbar and combined scoliosis) involved this reduced pulmonary capacity, with
      moderate-angulated scoliosis having a negative impact. At the beginning of brace
      treatment, the loss of real vital capacity with brace (0.3 litres) was 10% lower
      than without brace.At CMCR removal, the FVC had increased by 0.4 litre (21% +/-
      4.2% compared to the initial value). The theoretical value had increased by 3%.
      This positive evolution was most important in girls at a low Risser stage
      (0,1,2), and before 11 years of age. CONCLUSION: These results supported our
      approach of orthesis conception for adolescent idiopathic scoliosis which uses
      braces with mobile pads to preserve thorax and spine mobility.

PMID- 21880122
TI  - A pilot study of the use of near-patient C-Reactive Protein testing in the
      treatment of adult respiratory tract infections in one Irish general practice.
AB  - BACKGROUND: New approaches are being sought to safely reduce community antibiotic
      prescribing. A recent study demonstrated that CRP testing resulted in decreased
      antibiotic prescribing for lower respiratory tract infection in primary care.
      There is little other published primary care data available evaluating CRP in the
      treatment of lower respiratory tract infections in routine clinical practice.
      This pilot study aims to describe the performance of near-patient CRP testing, in
      a mixed payments health system. Specific areas to be reviewed included the
      integrity of the study protocol, testing of data collection forma and
      acceptability of the intervention. PATIENTS: Patients over the age of 18 years,
      with acute cough and/or sore throat with a duration of one month or less, in
      routine clinical practice. METHOD:  DESIGN: A pilot with a cross-sectional
      design. The first 60 recruited patients were treated with routine clinical
      management, and GP's had no access to a CRP test. For the subsequent 60 patients,
      access to CRP testing was available. PARTICIPANTS: 3 GP's in one Irish primary
      care practice recruited 120 patients, fulfilling the above criteria over five
      months, from January 1 to May 31, 2010. MAIN OUTCOME MEASURES: The primary
      outcome was antibiotic prescription at the index consultation. Secondary outcomes
      were the numbers of delayed prescriptions issued, patient satisfaction
      immediately after consultation and re-consultations and antibiotic prescriptions
      during 28 days follow-up. RESULTS: The protocol and data collection forms worked
      well and the intervention of CRP testing appeared acceptable. Thirty-five (58%)
      patients in the no-test group received antibiotic prescriptions compared to 27
      (45%) in the test group. Both groups demonstrated similarly high level of patient
      satisfaction (85%). Fourteen (23%) patients in the CRP test group re-attended
      within 28 days compared to 9 (15%) in the no-CRP test group. CONCLUSION: This
      pilot study confirms the potential feasibility of a full trial in Irish general
      practice. Further consideration of possible increased re-attendance rates in a
      mixed payments health system is appropriate. We intend to pursue a larger trial
      in a newly established regional primary care research network.

PMID- 21880123
TI  - Long-term results after Boston brace treatment in late-onset juvenile and
      adolescent idiopathic scoliosis.
AB  - BACKGROUND: It is recommended that research in patients with idiopathic scoliosis
      should focus on short- and long-term patient-centred outcome. The aim of the
      present study was to evaluate outcome in patients with late-onset juvenile or
      adolescent idiopathic scoliosis 16 years or more after Boston brace treatment.
      METHODS: 272 (78%) of 360 patients, 251 (92%) women, responded to follow-up
      examination at a mean of 24.7 (range 16 - 32) years after Boston brace treatment.
      Fifty-eight (21%) patients had late-onset juvenile and 214 had adolescent
      idiopathic scoliosis. All patients had clinical and radiological examination and
      answered a standardised questionnaire including work status, demographics,
      General Function Score (GFS) (100 - worst possible) and Oswestry Disability Index
      (ODI) (100 - worst possible), EuroQol (EQ-5D) (1 - best possible), EQ-VAS (100 -
      best possible), and Scoliosis Research Society - 22 (SRS - 22) (5 - best
      possible). RESULTS: The mean age at follow-up was 40.4 (31-48) years. The
      prebrace major curve was in average 33.2 (20 - 57) degrees . At weaning and at
      the last follow-up the corresponding values were 28.3 (1 - 58) degrees  and 32.5
      (7 - 80) degrees , respectively. Curve development was similar in patients with
      late-onset juvenile and adolescent start. The prebrace curve increased > 5
      degrees  in 31% and decreased > 5 degrees  in 26%. Twenty-five patients had
      surgery. Those who did not attend follow-up (n = 88) had a lower mean curve at
      weaning: 25.4 (6-53) degrees . Work status was 76% full-time and 10% part-time.
      Eighty-seven percent had delivered a baby, 50% had pain in pregnancy. The mean
      (SD) GFS was 7.4 (10.8), ODI 9.3 (11.0), EQ-5D 0.82 (0.2), EQ-VAS 77.6 (17.8),
      SRS-22: pain 4.1 (0.8), mental health 4.1 (0.6), self-image 3.7 (0.7), function
      4.0 (0.6), satisfaction with treatment 3.7 (1.0). Surgical patients had
      significantly reduced scores for SRS-physical function and self-image, and
      patients with curves >= 45 degrees  had reduced self-image. CONCLUSION: Long-term
      results were satisfactory in most braced patients and similar in late-onset
      juvenile and idiopathic adolescent scoliosis.

PMID- 21880124
TI  - Iron restriction induces preferential down-regulation of H(2)-consuming over H(2)
      evolving reactions during fermentative growth of Escherichia coli.
AB  - BACKGROUND: Escherichia coli synthesizes three anaerobically inducible [NiFe]
      hydrogenases (Hyd). All three enzymes have a [NiFe]-cofactor in the large subunit
      and each enzyme also has an iron-sulfur-containing small subunit that is required
      for electron transfer. In order to synthesize functionally active Hyd enzymes
      iron must be supplied to the maturation pathways for both the large and small
      subunits. The focus of this study was the analysis of the iron uptake systems
      required for synthesis of active Hyd-1, Hyd-2 and Hyd-3 during fermentative
      growth. RESULTS: A transposon-insertion mutant impaired in hydrogenase enzyme
      activity was isolated. The mutation was in the feoB gene encoding the ferrous
      iron transport system. The levels of both hydrogen-oxidizing enzymes Hyd-1 and
      Hyd-2 as determined by specific in-gel activity staining were reduced at least 10
      fold in the mutant after anaerobic fermentative growth in minimal medium, while
      the hydrogen-evolving Hyd-3 activity was less severely affected. Supplementation
      of the growth medium with ferric iron, which is taken up by e.g. the siderophore
      enterobactin, resulted in phenotypic complementation of the feoB mutant. Growth
      in rich medium demonstrated that a mutant lacking both the ferrous iron transport
      system and enterobactin biosynthesis (entC) was devoid of Hyd-1 and Hyd-2
      activity but retained some hydrogen-evolving Hyd-3 activity. Analysis of crude
      extracts derived from the feoB entC double null mutant revealed that the large
      subunits of the hydrogen-oxidizing enzymes Hyd-1 and Hyd-2 were absent. Analysis
      of lacZ fusions demonstrated, however, that expression of the hya, hyb and hyc
      operons was reduced only by maximally 50% in the mutants compared with the wild
      type. CONCLUSIONS: Our findings demonstrate that the ferrous iron transport
      system is the principal route of iron uptake for anaerobic hydrogenase
      biosynthesis, with a contribution from the ferric-enterobactin system. Hydrogen
      oxidizing enzyme function was abolished in a feoB entC double mutant and this
      appears to be due to post-translational effects. The retention of residual
      hydrogen-evolving activity, even in the feoB entC double null mutant suggests
      that sufficient iron can be scavenged to synthesize this key fermentative enzyme
      complex in preference to the hydrogen-uptake enzymes.

PMID- 21880125
TI  - Severe influenza cases in paediatric intensive care units in Germany during the
      pre-pandemic seasons 2005 to 2008.
AB  - BACKGROUND: Data on complications in children with seasonal influenza virus
      infection are limited. We initiated a nation-wide three-year surveillance of
      children who were admitted to a paediatric intensive care unit (PICU) with severe
      seasonal influenza. METHODS: From October 2005 to July 2008, active surveillance
      was performed using an established reporting system for rare diseases (ESPED)
      including all paediatric hospitals in Germany. Cases to be reported were
      hospitalized children < 17 years of age with laboratory-confirmed influenza
      treated in a PICU or dying in hospital. RESULTS: Twenty severe influenza
      associated cases were reported from 14 PICUs during three pre-pandemic influenza
      seasons (2005-2008). The median age of the patients (12 males/8 females) was 7.5
      years (range 0.1-15 years). None had received vaccination against influenza. In
      14 (70%) patients, the infection had been caused by influenza A and in five (25%)
      by influenza B; in one child (5%) the influenza type was not reported. Patients
      spent a median of 19 (IQR 12-38) days in the hospital and a median of 11 days
      (IQR 6-18 days) in the PICU; 10 (50%) needed mechanical ventilation. Most
      frequent diagnoses were influenza-associated pneumonia (60%),
      bronchitis/bronchiolitis (30%), encephalitis/encephalopathy (25%), secondary
      bacterial pneumonia (25%), and ARDS (25%). Eleven (55%) children had chronic
      underlying medical conditions, including 8 (40%) with chronic pulmonary diseases.
      Two influenza A- associated deaths were reported: i) an 8-year old boy with
      pneumococcal encephalopathy following influenza infection died from cerebral
      edema, ii) a 14-year-old boy with asthma bronchiale, cardiac malformation and
      Addison's disease died from cardiac and respiratory failure. For nine (45%)
      patients, possibly permanent sequelae were reported (3 neurological, 3 pulmonary,
      3 other sequelae). CONCLUSIONS: Influenza-associated pneumonia and secondary
      bacterial infections are relevant complications of seasonal influenza in Germany.
      The incidence of severe influenza cases in PICUs was relatively low. This may be
      either due to the weak to moderate seasonal influenza activity during the years
      2005 to 2008 or due to under-diagnosis of influenza by physicians. Fifty% of the
      observed severe cases might have been prevented by following the recommendations
      for vaccination of risk groups in Germany.

PMID- 21880126
TI  - At last, a Pennsylvanian stem-stonefly (Plecoptera) discovered.
AB  - BACKGROUND: Stem-relatives of many winged insect orders have been identified
      among Pennsylvanian fossils (Carboniferous Period). Owing to their presumed
      'basal' position in insect phylogeny, stoneflies were expected to occur at this
      period. However, no relative has ever been designated convincingly. RESULTS: In
      this paper, we report specimens belonging to a new fossil insect species
      collected from the Tupo Formation (Pennsylvanian; China). The wing venation of
      Gulou carpenteri gen. et sp. nov. exhibits character states diagnostic of the
      order Plecoptera, but lack character states shared by unequivocal representatives
      of the order. Derived from this identification, the delimitation of the fossil
      species is ascertained based on comparison of several extant stonefly species.
      This comparative analysis allowed a trait present in G. carpenteri gen. et sp.
      nov., but rarely occurring in extant species, to be documented and highlighted as
      atavistic. Affinities of taxa formerly proposed as putative stem-stoneflies are
      reconsidered in the light of the new discovery. CONCLUSIONS: Gulou carpenteri
      gen. et sp. nov. is considered the only genuine Plecoptera reported from the
      Pennsylvanian. Continuing efforts on the systematics of Pennsylvanian winged
      insects indicate a fauna more diverse than previously appreciated. It suggests
      that insects already had a long, yet undocumented, history by this time.

PMID- 21880127
TI  - Prevalence and characteristics of depressive disorders in early adolescents in
      central Norway.
AB  - BACKGROUND: Prevalence of depressive disorders among adolescents has varied
      across studies. The present study aims to assess current and lifetime prevalence
      and characteristics of adolescent Major Depressive Disorder (MDD), Dysthymia and
      Depression NOS among adolescents in Central Norway in addition to socio
      demographics and use of mental health care. METHOD: In the Youth and Mental
      Health Study a representative sample of 2432 junior high school students (mean
      age 14.9 years, SD = 0.6) from two counties in Central Norway were screened with
      the Mood and Feelings Questionnaire (MFQ). A subset of 345 of these adolescents
      (72.5% girls), 220 high scorers (MFQ = > 26), 74 middle scorers (MFQ 7-25), and
      50 low scorers (MFQ < 7), 1 unknown score, were drawn and interviewed with the
      Kiddie SADS-PL (Present-Life Version). In all, 79% had parental interviews as
      well. All estimates of prevalence rates and population shares were weighted back
      using a sandwich estimator to yield true population estimates. RESULTS: Almost
      one in four subjects (23%) had life-time depression. Prevalences of current Major
      Depressive Disorder (MDD), Dysthymia and "Double depression" were 2.6%, 1.0% and
      0.6%, respectively, and for Depression NOS 6.3%.All depressive disorders were
      characterized by long duration of episodes with large variations, and for any
      depressive disorder onset before 12 years of age. In multivariate analyses MDD
      and Dysthymia were most strongly associated with gender and not living with both
      biological parents. There was no gender difference for Depression NOS. Although a
      considerable number of depressed subjects had received mental health care, the
      reason for contact with services was seldom due to affective symptoms. Less than
      20% had been in contact with specialist mental health services. CONCLUSION: High
      rates of Depression NOS, early onset of depressive episodes, long duration, and
      low use of specialized services point to the need for improved diagnostic
      assessment and treatment for young individuals.

PMID- 21880128
TI  - Prevalence and psychopathological characteristics of depression in consecutive
      otorhinolaryngologic inpatients.
AB  - BACKGROUND: High prevalence of depression has been reported in
      otorhinolaryngologic patients (ORL). However, studies using a semi-structured
      interview to determine the prevalence of depression in ORL are lacking. Therefore
      the present study sought to determine the depression prevalence in ORL applying a
      semi-structured diagnostic interview and to further characterize the
      pathopsychological and demographic characteristics of depression in these
      patients. METHODS: One-hundred inpatients of the otorhinolaryngologic department
      of a German university hospital participated voluntarily (age M = 38.8 years, SD
      = 13.9; 38.0% female). Depression was assessed using a clinical interview in
      which the International Diagnostic Checklist for depression (IDCL) was applied.
      Patients completed the Brief Symptom Inventory (BSI) which constitutes three
      composite scores and nine symptom scales and the Beck Depression Inventory (BDI).
      Multivariate analyses of variance, correlations and effect sizes were conducted.
      RESULTS: A prevalence of depression of 21.0% was determined, 38.0% of the
      depressed patients were female. Depressed patients showed higher scores on the
      BSI-scales "interpersonal sensitivity", "depression", "anxiety", "phobic anxiety"
      and "psychoticism" with medium effect sizes. CONCLUSIONS: High prevalence of
      depression was found which is in accordance with results of prior studies.
      Depressed patients showed higher psychological distress as compared to non
      depressed patients. The results call for carrying on in engaging in depression
      research and routine depression screening in ORL.

PMID- 21880129
TI  - A novel reporter of notch signalling indicates regulated and random Notch
      activation during vertebrate neurogenesis.
AB  - BACKGROUND: Building the complex vertebrate nervous system involves the regulated
      production of neurons and glia while maintaining a progenitor cell population.
      Neurogenesis starts asynchronously in different regions of the embryo and occurs
      over a long period of time, allowing progenitor cells to be exposed to multiple
      extrinsic signals that regulate the production of different cell types. Notch
      mediated cell-cell signalling is one of the mechanisms that maintain the
      progenitor pool, however, little is known about how the timing of Notch
      activation is related to the cell cycle and the distinct modes of cell division
      that generate neurons. An essential tool with which to investigate the role of
      Notch signalling on cell by cell basis is the development a faithful reporter of
      Notch activity. RESULTS: Here we present a novel reporter for Notch activity
      based on the promoter of the well characterised Notch target chick Hes5-1,
      coupled with multiple elements that confer instability, including a destabilized
      nuclear Venus fluorescent protein and the 3' untranslated region (UTR) of Hes5-1.
      We demonstrate that this reporter faithfully recapitulates the endogenous
      expression of Hes5-1 and that it robustly responds to Notch activation in the
      chick neural tube. Analysis of the patterns of Notch activity revealed by this
      reporter indicates that although Notch is most frequently activated prior to
      mitosis it can be activated at any time within the cell cycle. Notch active
      progenitors undergoing mitosis generate two daughters that both continue to
      experience Notch signalling. However, cells lacking Notch activity before and
      during mitosis generate daughters with dissimilar Notch activity profiles.
      CONCLUSIONS: A novel Notch reporter with multiple destabilisation elements
      provides a faithful read-out of endogenous Notch activity on a cell-by-cell
      basis, as neural progenitors progress through the cell cycle in the chick neural
      tube. Notch activity patterns in this cell population provide evidence for
      distinct Notch signalling dynamics underlying different cell division modes and
      for the involvement of random initiation of Notch signalling within the
      neuroepithelium. These findings highlight the importance of single-cell analysis
      in the study of the complexity of Notch activity and provide new insights into
      the mechanisms underlying cell fate decisions in neural progenitors.

PMID- 21880130
TI  - Influence of the oxide layer for growth of self-assisted InAs nanowires on
      Si(111).
AB  - The growth of self-assisted InAs nanowires (NWs) by molecular beam epitaxy (MBE)
      on Si(111) is studied for different growth parameters and substrate preparations.
      The thickness of the oxide layer present on the Si(111) surface is observed to
      play a dominant role. Systematic use of different pre-treatment methods provides
      information on the influence of the oxide on the NW morphology and growth rates,
      which can be used for optimizing the growth conditions. We show that it is
      possible to obtain 100% growth of vertical NWs and no parasitic bulk structures
      between the NWs by optimizing the oxide thickness. For a growth temperature of
      460 degrees C and a V/III ratio of 320 an optimum oxide thickness of 9 +/- 3 A is
      found.

PMID- 21880131
TI  - Direct association between pharyngeal viral secretion and host cytokine response
      in severe pandemic influenza.
AB  - BACKGROUND: Severe disease caused by 2009 pandemic influenza A/H1N1virus is
      characterized by the presence of hypercytokinemia. The origin of the exacerbated
      cytokine response is unclear. As observed previously, uncontrolled influenza
      virus replication could strongly influence cytokine production. The objective of
      the present study was to evaluate the relationship between host cytokine
      responses and viral levels in pandemic influenza critically ill patients.
      METHODS: Twenty three patients admitted to the ICU with primary viral pneumonia
      were included in this study. A quantitative PCR based method targeting the M1
      influenza gene was developed to quantify pharyngeal viral load. In addition, by
      using a multiplex based assay, we systematically evaluated host cytokine
      responses to the viral infection at admission to the ICU. Correlation studies
      between cytokine levels and viral load were done by calculating the Spearman
      correlation coefficient. RESULTS: Fifteen patients needed of intubation and
      ventilation, while eight did not need of mechanical ventilation during ICU
      hospitalization. Viral load in pharyngeal swabs was 300 fold higher in the group
      of patients with the worst respiratory condition at admission to the ICU.
      Pharyngeal viral load directly correlated with plasma levels of the pro
      inflammatory cytokines IL-6, IL-12p70, IFN-gamma, the chemotactic factors MIP
      1beta, GM-CSF, the angiogenic mediator VEGF and also of the immuno-modulatory
      cytokine IL-1ra (p < 0.05). Correlation studies demonstrated also the existence
      of a significant positive association between the levels of these mediators,
      evidencing that they are simultaneously regulated in response to the virus.
      CONCLUSIONS: Severe respiratory disease caused by the 2009 pandemic influenza
      virus is characterized by the existence of a direct association between viral
      replication and host cytokine response, revealing a potential pathogenic link
      with the severe disease caused by other influenza subtypes such as H5N1.

PMID- 21880132
TI  - Neoadjuvant capecitabine, radiotherapy, and bevacizumab (CRAB) in locally
      advanced rectal cancer: results of an open-label phase II study.
AB  - BACKGROUND: Preoperative capecitabine-based chemoradiation is a standard
      treatment for locally advanced rectal cancer (LARC). Here, we explored the safety
      and efficacy of the addition of bevacizumab to capecitabine and concurrent
      radiotherapy for LARC. METHODS: Patients with MRI-confirmed stage II/III rectal
      cancer received bevacizumab 5 mg/kg i.v. 2 weeks prior to neoadjuvant
      chemoradiotherapy followed by bevacizumab 5 mg/kg on Days 1, 15 and 29,
      capecitabine 825 mg/m2 twice daily on Days 1-38, and concurrent radiotherapy 50.4
      Gy (1.8 Gy/day, 5 days/week for 5 weeks + three 1.8 Gy/day), starting on Day 1.
      Total mesorectal excision was scheduled 6-8 weeks after completion of
      chemoradiotherapy. Tumour regression grades (TRG) were evaluated on surgical
      specimens according to Dworak. The primary endpoint was pathological complete
      response (pCR). RESULTS: 61 patients were enrolled (median age 60 years [range 31
      80], 64% male). Twelve patients (19.7%) had T3N0 tumours, 1 patient T2N1, 19
      patients (31.1%) T3N1, 2 patients (3.3%) T2N2, 22 patients (36.1%) T3N2 and 5
      patients (8.2%) T4N2. Median tumour distance from the anal verge was 6 cm (range
      0-11). Grade 3 adverse events included dermatitis (n = 6, 9.8%), proteinuria (n =
      4, 6.5%) and leucocytopenia (n = 3, 4.9%). Radical resection was achieved in 57
      patients (95%), and 42 patients (70%) underwent sphincter-preserving surgery. TRG
      4 (pCR) was recorded in 8 patients (13.3%) and TRG 3 in 9 patients (15.0%). T-, N
      and overall downstaging rates were 45.2%, 73.8%, and 73.8%, respectively.
      CONCLUSIONS: This study demonstrates the feasibility of preoperative
      chemoradiotherapy with bevacizumab and capecitabine. The observed adverse events
      of neoadjuvant treatment are comparable with those previously reported, but the
      pCR rate was lower.

PMID- 21880133
TI  - The frequency of microscopic and focal active colitis in patients with irritable
      bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a chronic functional bowel
      disorder. The frequency of microscopic colitis and focal active colitis in the
      colonic mucosa has been investigated in IBS patients. METHODS: Between June 2007
      and September 2010, 378 patients (between 16 and 84 years) were recruited
      prospectively. Of these 378 patients, 226 patients were diagnosed with IBS using
      the Rome III criteria. 152 control patients were also enrolled who were
      undergoing colonoscopy for colorectal cancer screening or investigation of
      anemia. Histopathological abnormalities identified during colonoscopy were
      compared between the IBS and control groups. RESULTS: The average age of the IBS
      group was 46.13 +/- 14.16 years and and the average age of the control group was
      57.01 +/- 13.07 years. The prevalence of microscopic colitis (MC) in the diarrhea
      predominant and the mixed subgroup of IBS patients was 4.32% (7/162) whereas in
      all IBS patients, the prevalence was 3.09% (7/226). MC was not found in the 152
      control cases, (p = 0.045). Lymphocytic colitis was seen in 7 IBS patients, with
      1 case in the mixed group and 6 cases in the diarrhea group and there was a
      significant difference in the frequency of lymphocytic colitis between the IBS
      subgroups (p < 0.01). Focal active colitis was found in 6.6% (15/226) of the IBS
      patients and in none of the controls (p < 0.01), and there was no differences
      between IBS subtypes. CONCLUSION: Microscopic colitis was more often found in the
      diarrhea predominant/mixed subgroups of IBS patients and in patients who were
      older women. In patients who are older woman with non-constipated IBS, it may be
      reasonable to perform a biopsy to screen for microscopic colitis. Focal active
      colitis was significantly increased in patients with IBS compared to controls.

PMID- 21880134
TI  - Constitutive expression of cathepsin K in the human intervertebral disc: new
      insight into disc extracellular matrix remodeling via cathepsin K and receptor
      activator of nuclear factor-kappaB ligand.
AB  - INTRODUCTION: Cathepsin K is a recently discovered cysteine protease which
      cleaves the triple helical domains of type I to II collagen. It has been shown to
      be up-regulated in synovial tissue from osteoarthritic and rheumatoid patients,
      and is a component in normal and nonarthritic cartilage, where it increases with
      aging. Studies on heart valve development have recently shown that receptor
      activator of nuclear factor-kappaB ligand (RANKL) acts during valve remodeling to
      promote cathepsin K expression. Since extracellular matrix remodeling is a
      critical component of disc structure and biomechanical function, we hypothesized
      that cathepsin K and RANKL may be present in the human intervertebral disc.
      METHODS: Studies were performed following approval of the authors' Human Subjects
      Institutional Review Board. Six annulus specimens from healthier Thompson grade I
      to II discs, and 12 specimens from more degenerate grade III to IV discs were
      utilized in microarray analysis of RANKL and cathepsin K gene expression.
      Immunohistochemistry was also performed on 15 additional disc specimens to assess
      the presence of RANKL and cathepsin K. RESULTS: Cathepsin K gene expression was
      significantly greater in more degenerated grade III to IV discs compared to
      healthier grade I to II discs (P = 0.001). RANKL was also identified with
      immunohistochemistry and molecular analyses. RANKL gene expression was also
      significantly greater in more degenerated discs compared to healthier ones (P =
      0.0001). A significant linear positive correlation was identified between
      expression of cathepsin K and RANKL (r(2) = 92.2; P < 0.0001). CONCLUSIONS:
      Extracellular matrix remodeling is a key element of disc biology. Our use of an
      appropriate antibody and gene expression studies showed that cathepsin K is
      indeed present in the human intervertebral disc. Immunolocalization and molecular
      analyses also confirmed that RANKL is present in the human disc. Expression of
      RANKL was found to be significantly greater in more degenerated compared to
      healthier discs (P = 0.0001). Cathepsin K gene expression levels showed a
      positive, significant correlation with RANKL expression. Based on these data, we
      propose that cathepsin K plays a significant role in disc matrix remodeling and
      in matrix degradation in the proinflammatory cytokine-rich microenvironment of
      the degenerating disc.

PMID- 21880135
TI  - Repression of GW/P body components and the RNAi microprocessor impacts primary
      ciliogenesis in human astrocytes.
AB  - BACKGROUND: In most cells, the centriolar component of the centrosome can
      function as a basal body supporting the formation of a primary cilium, a non
      motile sensory organelle that monitors information from the extracellular matrix
      and relays stimuli into the cell via associated signaling pathways. Defects in
      the formation and function of primary cilia underlie multiple human diseases and
      are hallmarks of malignancy. The RNA silencing pathway is involved in the post
      transcriptional silencing of > 50% of mRNA that occurs within GW/P bodies. GW/P
      bodies are found throughout the cytoplasm and previously published live cell
      imaging data suggested that in a malignant cell type (U2OS), two GW/P bodies
      reside at the centrosome during interphase. This led us to investigate if a
      similar relationship exists in primary cells and if the inhibition of the miRNA
      pathway impairs primary cilium formation. RESULTS: Two GW/P bodies as marked by
      GW182 and hAgo2 colocalized to the basal body of primary human astrocytes as well
      as human synoviocytes during interphase and specifically with the distal end of
      the basal body in the pericentriolar region. Since it is technically challenging
      to examine the two centrosomal GW/P bodies in isolation, we investigated the
      potential relationship between the global population of GW/P bodies and primary
      ciliogenesis. Astrocytes were transfected with siRNA directed to GW182 and hAgo2
      and unlike control astrocytes, a primary cilium was no longer associated with the
      centrosome as detected in indirect immunofluorescence assays. Ultrastructural
      analysis of siRNA transfected astrocytes revealed that knock down of GW182,
      hAgo2, Drosha and DGCR8 mRNA did not affect the appearance of the earliest stage
      of ciliogenesis but did prevent the formation and elongation of the ciliary
      axoneme. CONCLUSIONS: This study confirms and extends a previously published
      report that GW/P bodies reside at the centrosome in U2OS cells and documents that
      GW/P bodies are resident at the centrosome in diverse non-malignant cells.
      Further, our study demonstrates that repression of key effector proteins in the
      post-transcriptional miRNA pathway impairs primary cilium formation.

PMID- 21880136
TI  - The equity dimension in evaluations of the quality and outcomes framework: a
      systematic review.
AB  - BACKGROUND: Pay-for-performance systems raise concerns regarding inequity in
      health care because providers might select patients for whom targets can easily
      be reached. This paper aims to describe the evolution of pre-existing (in)equity
      in health care in the period after the introduction of the Quality and Outcomes
      Framework (QOF) in the UK and to describe (in)equities in exception reporting. In
      this evaluation, a theory-based framework conceptualising equity in terms of
      equal access, equal treatment and equal treatment outcomes for people in equal
      need is used to guide the work. METHODS: A systematic MEDLINE and Econlit search
      identified 317 studies. Of these, 290 were excluded because they were not related
      to the evaluation of QOF, they lacked an equity dimension in the evaluation,
      their qualitative research focused on experiences or on the nature of the
      consultation, or unsuitable methodology was used to pronounce upon equity after
      the introduction of QOF. RESULTS: None of the publications (n = 27) assessed
      equity in access to health care. Concerning equity in treatment and
      (intermediate) treatment outcomes, overall quality scores generally improved. For
      the majority of the observed indicators, all citizens benefit from this
      improvement, yet the extent to which different patient groups benefit tends to
      vary and to be highly dependent on the type and complexity of the indicator(s)
      under study, the observed patient group(s) and the characteristics of the study.
      In general, the introduction of QOF was favourable for the aged and for males.
      Total QOF scores did not seem to vary according to ethnicity. For deprivation,
      small but significant residual differences were observed after the introduction
      of QOF favouring less deprived groups. These differences are mainly due to
      differences at the practice level. The variance in exception reporting according
      to gender and socio-economic position is low. CONCLUSIONS: Although QOF seems not
      to be socially selective at first glance, this does not mean QOF does not
      contribute to the inverse care law. Introducing different targets for specific
      patient groups and including appropriate, non-disease specific and patient
      centred indicators that grasp the complexity of primary care might refine the
      equity dimension of the evaluation of QOF. Also, information on the actual uptake
      of care, information at the patient level and monitoring of individuals' health
      care utilisation tracks could make large contributions to an in-depth evaluation.
      Finally, evaluating pay-for-quality initiatives in a broader health systems
      impact assessment strategy with equity as a full assessment criterion is of
      utmost importance.

PMID- 21880137
TI  - Epithelial-Mesenchymal Transition in tumor microenvironment.
AB  - The epithelial to mesenchymal transition (EMT) plays crucial roles in the
      formation of the body plan and also in the tumor invasion process. In addition,
      EMT also causes disruption of cell-cell adherence, loss of apico-basal polarity,
      matrix remodeling, increased motility and invasiveness in promoting tumor
      metastasis. The tumor microenvironment plays an important role in facilitating
      cancer metastasis and may induce the occurrence of EMT in tumor cells. A large
      number of inflammatory cells infiltrating the tumor site, as well as hypoxia
      existing in a large area of tumor, in addition many stem cells present in tumor
      microenvironment, such as cancer stem cells (CSCs), mesenchymal stem cells
      (MSCs), all of these may be the inducers of EMT in tumor cells. The signaling
      pathways involved in EMT are various, including TGF-beta, NF-kappaB, Wnt, Notch,
      and others. In this review, we discuss the current knowledge about the role of
      the tumor microenvironment in EMT and the related signaling pathways as well as
      the interaction between them.

PMID- 21880138
TI  - A review of mixed malaria species infections in anopheline mosquitoes.
AB  - BACKGROUND: In patients with malaria mixed species infections are common and
      under reported. In PCR studies conducted in Asia mixed infection rates often
      exceed 20%. In South-East Asia, approximately one third of patients treated for
      falciparum malaria experience a subsequent Plasmodium vivax infection with a time
      interval suggesting relapse. It is uncertain whether the two infections are
      acquired simultaneously or separately. To determine whether mixed species
      infections in humans are derived from mainly from simultaneous or separate
      mosquito inoculations the literature on malaria species infection in wild
      captured anopheline mosquitoes was reviewed. METHODS: The biomedical literature
      was searched for studies of malaria infection and species identification in
      trapped wild mosquitoes and artificially infected mosquitoes. The study location
      and year, collection methods, mosquito species, number of specimens, parasite
      stage examined (oocysts or sporozoites), and the methods of parasite detection
      and speciation were tabulated. The entomological results in South East Asia were
      compared with mixed infection rates documented in patients in clinical studies.
      RESULTS: In total 63 studies were identified. Individual anopheline mosquitoes
      were examined for different malaria species in 28 of these. There were 14 studies
      from Africa; four with species evaluations in individual captured mosquitoes
      (SEICM). One study, from Ghana, identified a single mixed infection. No mixed
      infections were identified in Central and South America (seven studies, two
      SEICM). 42 studies were conducted in Asia and Oceania (11 from Thailand; 27
      SEICM). The proportion of anophelines infected with Plasmodium falciparum
      parasites only was 0.51% (95% CI: 0.44 to 0.57%), for P. vivax only was 0.26%
      (95% CI: 0.21 to 0.30%), and for mixed P. falciparum and P. vivax infections was
      0.036% (95% CI: 0.016 to 0.056%). The proportion of mixed infections in
      mosquitoes was significantly higher than expected by chance (P < 0.001), but was
      one fifth of that sufficient to explain the high rates of clinical mixed
      infections by simultaneous inoculation. CONCLUSIONS: There are relatively few
      data on mixed infection rates in mosquitoes from Africa. Mixed species malaria
      infections may be acquired by simultaneous inoculation of sporozoites from
      multiply infected anopheline mosquitoes but this is relatively unusual. In South
      East Asia, where P. vivax infection follows P. falciparum malaria in one third of
      cases, the available entomological information suggests that the majority of
      these mixed species malaria infections are acquired from separate inoculations.

PMID- 21880140
TI  - Correlation between antibutyrylcholinesterasic and antioxidant activities of
      three aqueous extracts from Tunisian Rhus pentaphyllum.
AB  - For centuries, plants have been used in traditional medicines and there has been
      recent interest in the chemopreventive properties of compounds derived from
      plants. In the present study, we investigated the antibutyrylcholinestrasic (anti
      BuChE) and antioxidant (against some free radicals) activities of extracts from
      Rhus pentaphyllum. Aqueous extracts were prepared from powdered R. pentaphyllum
      roots, leaves and seeds and characterized for the presence of tannins, flavonoids
      and coumarins. Seeds aqueous extract contained the highest quantities of both
      flavonoids and tannins (21.12% and 17.45% respectively). In the same way, seeds
      extracts displayed remarkable inhibition against BuChE over 95%, at 100 MUg/ml
      and with IC50 0.74 MUg/ml. In addition, compared to leaves and roots extracts,
      seeds aqueous extract revealed relatively strong antiradical activity towards the
      ABTS.+ (IC50 = 0.25 MUg/ml) and DPPH (IC50 = 2.71 MUg/ml) free radicals and
      decreased significantly the reactive oxygen species such O2.- (IC50 = 2.9 MUg/ml)
      formation evaluated by the non-enzymatic generating O2.- system (Nitroblue
      tetrazolium/riboflavine). These data suggest that the anti-BuChE activities
      mechanism of these extracts occurs through a free radical scavenging
      capacities.The present study indicates that extracts of Rhus pentaphyllum leaves,
      seeds and roots are a significant source of compounds, such as tannins,
      flavonoids and coumarins, with anti-BuChE and antioxidant activities, and thus
      may be useful for chemoprevention.

PMID- 21880139
TI  - Evidence for maintenance of sex determinants but not of sexual stages in red
      yeasts, a group of early diverged basidiomycetes.
AB  - BACKGROUND: The red yeasts are an early diverged group of basidiomycetes
      comprising sexual and asexual species. Sexuality is based on two compatible
      mating types and sexual identity is determined by MAT loci that encode
      homeodomain transcription factors, peptide pheromones and their receptors. The
      objective of the present study was to investigate the presence and integrity of
      MAT genes throughout the phylogenetic diversity of red yeasts belonging to the
      order Sporidiobolales. RESULTS: We surveyed 18 sexual heterothallic and self
      fertile species and 16 asexual species. Functional pheromone receptor homologues
      (STE3.A1 and STE3.A2) were found in multiple isolates of most of the sexual and
      asexual species. For each of the two mating types, sequence comparisons with
      whole-genome data indicated that synteny tended to be conserved along the
      pheromone receptor region. For the homeodomain transcription factor, likelihood
      methods suggested that diversifying selection acting on the self/non-self
      recognition region promotes diversity in sexual species, while rapid evolution
      seems to be due to relaxed selection in asexual strains. CONCLUSIONS: The
      majority of both sexual and asexual species of red yeasts have functional
      pheromone receptors and homeodomain homologues. This and the frequent existence
      of asexual strains within sexual species, makes the separation between sexual and
      asexual species imprecise. Events of loss of sexuality seem to be recent and
      frequent, but not uniformly distributed within the Sporidiobolales. Loss of sex
      could promote speciation by fostering the emergence of asexual lineages from an
      ancestral sexual stock, but does not seem to contribute to the generation of
      exclusively asexual lineages that persist for a long time.

PMID- 21880141
TI  - How is the New Public Management applied in the occupational health care system? 
      decision-makers' and OH personnel's views in Finland.
AB  - BACKGROUND: In many countries occupational health care system is in change.
      Occupational health studies are mainly focused on occupational health substance
      and content. This study offers new perspectives on municipal OHS and its
      operations from management perspective. AIM: The aim of this study is to analyse
      how New Public Management (NPM) doctrines are applied in the Finnish occupational
      health care system (OHS). The main focus is to describe and compare the views of
      decision-makers' and OH workers within the framework of NPM. METHODS: The data
      were collected by semi-structured interviews from 17 municipal decision-makers'
      and 26 municipal OH workers. Data was analyzed by examining coded data in a
      theory-driven way according to Hood's doctrine of NPM. RESULTS: The doctrines
      were not as compatible with the OH personnel view as with the decision-makers'
      view. Decision-makers and OH personnel highlighted the strict criteria required
      for operation evaluation. Moreover, decision-makers strongly accentuated
      professional management in the public sector and the reorganization of public
      sector units. These were not equally relevant in OH personnel views. In OH
      personnel views, other doctrines (more attention to performance and
      accomplishments, emphasizing and augmentation of the competition and better
      control of public expense and means test) were not similarly in evidence, only
      weak evidence was observed when their importance viewed as medium by decision
      makers. Neither of the respondents group kept the doctrine of management models
      of the private sector relevant. CONCLUSIONS: The NPM and Hoods doctrine fitted
      well with OH research. The doctrine brought out view differences and similarities
      between decision-makers and OH personnel. For example, policymakers highlighted
      more strongly the structural change by emphasizing professional management
      compared to OH personnel. The need for reorganization of municipal OH, regardless
      of different operational preconditions, was obvious for both decision-makers and
      OH personnel. The adaptation of more clarify management to a municipal context is
      not trouble-free. The municipality systemic structure, complex operational
      environment, and reconciliation of political and officer authority set challenges
      to management of municipalities.

PMID- 21880142
TI  - G-patch domain and KOW motifs-containing protein, GPKOW; a nuclear RNA-binding
      protein regulated by protein kinase A.
AB  - BACKGROUND: Post-transcriptional processing of pre-mRNA takes place in several
      steps and requires involvement of a number of RNA-binding proteins. How pre-mRNA
      processing is regulated is in large enigmatic. The catalytic (C) subunit of
      protein kinase A (PKA) is a serine/threonine kinase, which regulates numerous
      cellular processes including pre-mRNA splicing. Despite that a significant
      fraction of the C subunit is found in splicing factor compartments in the
      nucleus, there are no indications of a direct interaction between RNA and PKA.
      Based on this we speculate if the specificity of the C subunit in regulating pre
      mRNA splicing may be mediated indirectly through other nuclear proteins. RESULTS:
      Using yeast two-hybrid screening with the PKA C subunit Cbeta2 as bait, we
      identified the G-patch domain and KOW motifs-containing protein (GPKOW), also
      known as the T54 protein or MOS2 homolog, as an interaction partner for Cbeta2.
      We demonstrate that GPKOW, which contains one G-patch domain and two KOW motifs,
      is a nuclear RNA-binding protein conserved between species. GPKOW contains two
      sites that are phosphorylated by PKA in vitro. By RNA immunoprecipitation and
      site directed mutagenesis of the PKA phosphorylation sites we revealed that GPKOW
      binds RNA in vivo in a PKA sensitive fashion. CONCLUSION: GPKOW is a RNA-binding
      protein that binds RNA in a PKA regulated fashion. Together with our previous
      results demonstrating that PKA regulates pre-mRNA splicing, our results suggest
      that PKA phosphorylation is involved in regulating RNA processing at several
      steps.

PMID- 21880143
TI  - Efficacy of long-lasting insecticidal nets in use in Macha, Zambia, against the
      local Anopheles arabiensis population.
AB  - BACKGROUND: The mosquito Anopheles arabiensis is the primary vector of Plasmodium
      falciparum in Macha, Zambia. A major portion of Zambia's current malaria control
      programme relies on long-lasting insecticide-treated nets (LLINs) and indoor
      residual spraying (IRS) with insecticides. Currently, the efficacy of these
      measures against An. arabiensis in Macha is unknown, and previous data has shown
      that An. arabiensis has continued to feed on human hosts, despite high ITN
      coverage. It is possible that this could be due to either decreased efficacy of
      ITNs in used in Macha, or pyrethroid resistance in the vector. METHODS: F1
      offspring of field-collected adult An. arabiensis were tested for insecticide
      resistance, using CDC bottle bioassays and deltamethrin ITN susceptibility
      assays. The mosquitoes were characterized for the knock-down resistance (kdr)
      allele by PCR. LLINs that had been in use for two years in nearby villages were
      collected and tested for residual deltamethrin concentration and net quality, and
      were used in bioassays against susceptible colonized Anopheles gambiae s.s.
      Keele. Additionally, a survey on ITN use and care was conducted among LLIN
      owners. RESULTS: In the F1 An. arabiensis field population, low levels of
      resistance to DDT and deltamethrin-treated net material were detected by
      bioassay, although the knock-down resistance (kdr) allele not present in the
      population. ITN evaluations revealed high variability in residual deltamethrin
      concentration, quality of the nets, and mosquito mortality in bioassays.
      Mortality against An. gambiae s.s. in bioassays was correlated with residual
      deltamethrin concentration, which was dependent upon the number of washes each
      net had received. CONCLUSIONS: Proper LLIN care was a strong determinant of LLIN
      efficacy, indicating that education on the importance of LLIN use and care is key
      when distributing nets. As there is little insecticide resistance in the local
      vector population, degradation of LLINs most likely allowed for continued human
      feeding by An. arabiensis. Continued monitoring and assessment of both the vector
      population and the efficacy of LLINs in use is necessary in order to
      appropriately modify vector control operations and prevent the development of
      pyrethroid resistance.

PMID- 21880144
TI  - Lysis-deficient phages as novel therapeutic agents for controlling bacterial
      infection.
AB  - BACKGROUND: Interest in phage therapy has grown over the past decade due to the
      rapid emergence of antibiotic resistance in bacterial pathogens. However, the use
      of bacteriophages for therapeutic purposes has raised concerns over the potential
      for immune response, rapid toxin release by the lytic action of phages, and
      difficulty in dose determination in clinical situations. A phage that kills the
      target cell but is incapable of host cell lysis would alleviate these concerns
      without compromising efficacy. RESULTS: We developed a recombinant lysis
      deficient Staphylococcus aureus phage P954, in which the endolysin gene was
      rendered nonfunctional by insertional inactivation. P954, a temperate phage, was
      lysogenized in S. aureus strain RN4220. The native endolysin gene on the prophage
      was replaced with an endolysin gene disrupted by the chloramphenicol acetyl
      transferase (cat) gene through homologous recombination using a plasmid
      construct. Lysogens carrying the recombinant phage were detected by growth in
      presence of chloramphenicol. Induction of the recombinant prophage did not result
      in host cell lysis, and the phage progeny were released by cell lysis with glass
      beads. The recombinant phage retained the endolysin-deficient genotype and formed
      plaques only when endolysin was supplemented. The host range of the recombinant
      phage was the same as that of the parent phage. To test the in vivo efficacy of
      the recombinant endolysin-deficient phage, immunocompromised mice were challenged
      with pathogenic S. aureus at a dose that results in 80% mortality (LD80).
      Treatment with the endolysin-deficient phage rescued mice from the fatal S.
      aureus infection. CONCLUSIONS: A recombinant endolysin-deficient staphylococcal
      phage has been developed that is lethal to methicillin-resistant S. aureus
      without causing bacterial cell lysis. The phage was able to multiply in lytic
      mode utilizing a heterologous endolysin expressed from a plasmid in the
      propagation host. The recombinant phage effectively rescued mice from fatal S.
      aureus infection. To our knowledge this is the first report of a lysis-deficient
      staphylococcal phage.

PMID- 21880145
TI  - Predictors of surgical site infections among patients undergoing major surgery at
      Bugando Medical Centre in Northwestern Tanzania.
AB  - BACKGROUND: Surgical site infection (SSI) continues to be a major source of
      morbidity and mortality in developing countries despite recent advances in
      aseptic techniques. There is no baseline information regarding SSI in our setting
      therefore it was necessary to conduct this study to establish the prevalence,
      pattern and predictors of surgical site infection at Bugando Medical Centre
      Mwanza (BMC), Tanzania. METHODS: This was a cross-sectional prospective study
      involving all patients who underwent major surgery in surgical wards between July
      2009 and March 2010. After informed written consent for the study and HIV
      testing, all patients who met inclusion criteria were consecutively enrolled into
      the study. Pre-operative, intra-operative and post operative data were collected
      using standardized data collection form. Wound specimens were collected and
      processed as per standard operative procedures; and susceptibility testing was
      done using disc diffusion technique. Data were analyzed using SPSS software
      version 15 and STATA. RESULTS: Surgical site infection (SSI) was detected in 65
      (26.0%) patients, of whom 56 (86.2%) and 9 (13.8%) had superficial and deep SSI
      respectively. Among 65 patients with clinical SSI, 56(86.2%) had positive aerobic
      culture. Staphylococcus aureus was the predominant organism 16/56 (28.6%); of
      which 3/16 (18.8%) were MRSA. This was followed by Escherichia coli 14/56 (25%)
      and Klebsiella pneumoniae 10/56 (17.9%). Among the Escherichia coli and
      Klebsiella pneumoniae isolates 9(64.3%) and 8(80%) were ESBL producers
      respectively. A total of 37/250 (14.8%) patients were HIV positive with a mean
      CD4 count of 296 cells/ml. Using multivariate logistic regression analysis,
      presence of pre-morbid illness (OR = 6.1), use of drain (OR = 15.3), use of
      iodine alone in skin preparation (OR = 17.6), duration of operation >= 3 hours
      (OR = 3.2) and cigarette smoking (OR = 9.6) significantly predicted surgical site
      infection (SSI) CONCLUSION: SSI is common among patients admitted in surgical
      wards at BMC and pre-morbid illness, use of drain, iodine alone in skin
      preparation, prolonged duration of the operation and cigarette smoking were found
      to predict SSI. Prevention strategies focusing on factors associated with SSI is
      necessary in order to reduce the rate of SSI in our setting.

PMID- 21880146
TI  - Mesothelin confers pancreatic cancer cell resistance to TNF-alpha-induced
      apoptosis through Akt/PI3K/NF-kappaB activation and IL-6/Mcl-1 overexpression.
AB  - BACKGROUND: Previous studies showed that mesothelin (MSLN) plays important roles
      in survival of pancreatic cancer (PC) cells under anchorage dependent/independent
      conditions as well as resistance to chemotherapy. The recent success of
      intratumorally-injected adeno-encoded, chemo/radiation-inducible-promoter driven
      hTNF-alpha, (TNFerade) + gemcitabine in pre-clinical models of PC have renewed
      interest in use of TNF-alpha as a therapeutic component. To help find additional
      factors which might affect the therapy, we examined the resistance of MSLN
      overexpressing pancreatic cancer cell lines to TNF-alpha-induced growth
      inhibition/apoptosis. METHODS: Stable MSLN overexpressing MIA PaCa-2 cells (MIA
      MSLN), stable MSLN-silenced AsPC-1 cells (AsPC-shMSLN) and other pancreatic cells
      (MIA-PaCa2, Panc 28, Capan-1, BxPC3, PL 45, Hs 766T, AsPC-1, Capan-2, Panc 48)
      were used. NF-kappaB activation was examined by western blots and luciferase
      reporter assay. TNF-alpha induced growth inhibition/apoptosis was measured by
      MTT, TUNEL assay and caspase activation. IL-6 was measured using luminex based
      assay. RESULTS: Compared to low endogenous MSLN-expressing MIA PaCa-2 and Panc 28
      cells, high endogenous MSLN-expressing Capan-1, BxPC3, PL 45, Hs 766T, AsPC-1,
      Capan-2, Panc 48 cells were resistant to TNF-alpha induced growth inhibition.
      Stable MSLN overexpressing MIA-PaCa2 cells (MIA-MSLN) were resistant to TNF-alpha
      induced apoptosis while stable MSLN-silenced AsPC1 cells (AsPC-shMSLN) were
      sensitive. Interestingly, TNF-alpha-treated MIA-MSLN cells showed increased cell
      cycle progression and cyclin A induction, both of which were reversed by caspase
      inhibition. We further found that MIA-MSLN cells showed increased expression of
      anti-apoptotic Bcl-XL and Mcl-1; deactivated (p-Ser75) BAD, and activated (p
      Ser70) Bcl-2. Constitutively activated NF-kappaB and Akt were evident in MIA-MSLN
      cells that could be suppressed by MSLN siRNA with a resultant increase in
      sensitivity of TNF-alpha induced apoptosis. Blocking NF-kappaB using IKK
      inhibitor wedelolactone also increased sensitivity to TNF-alpha-mediated
      cytotoxicity with concomitant decrease in Mcl-1. Blocking Akt using PI3K
      inhibitor also had a likewise effect presumably affecting cell cycle. MIA-MSLN
      cells produced increased IL-6 and were increased furthermore by TNF-alpha
      treatment. SiRNA-silencing of IL-6 increased TNF-alpha sensitivity of MIA-MSLN
      cells. CONCLUSIONS: Our study delineates a MSLN-Akt-NF-kappaB-IL-6-Mcl-1 survival
      axis that may be operative in PC cells, and might help cancer cells' survival in
      the highly inflammatory milieu evident in PC. Further, for the success of
      TNFerade + gemcitabine to be successful, we feel the simultaneous inhibition of
      components of this axis is also essential.

PMID- 21880147
TI  - An integrative approach to ortholog prediction for disease-focused and other
      functional studies.
AB  - BACKGROUND: Mapping of orthologous genes among species serves an important role
      in functional genomics by allowing researchers to develop hypotheses about gene
      function in one species based on what is known about the functions of orthologs
      in other species. Several tools for predicting orthologous gene relationships are
      available. However, these tools can give different results and identification of
      predicted orthologs is not always straightforward. RESULTS: We report a simple
      but effective tool, the Drosophila RNAi Screening Center Integrative Ortholog
      Prediction Tool (DIOPT; http://www.flyrnai.org/diopt), for rapid identification
      of orthologs. DIOPT integrates existing approaches, facilitating rapid
      identification of orthologs among human, mouse, zebrafish, C. elegans,
      Drosophila, and S. cerevisiae. As compared to individual tools, DIOPT shows
      increased sensitivity with only a modest decrease in specificity. Moreover, the
      flexibility built into the DIOPT graphical user interface allows researchers with
      different goals to appropriately 'cast a wide net' or limit results to highest
      confidence predictions. DIOPT also displays protein and domain alignments,
      including percent amino acid identity, for predicted ortholog pairs. This helps
      users identify the most appropriate matches among multiple possible orthologs. To
      facilitate using model organisms for functional analysis of human disease
      associated genes, we used DIOPT to predict high-confidence orthologs of disease
      genes in Online Mendelian Inheritance in Man (OMIM) and genes in genome-wide
      association study (GWAS) data sets. The results are accessible through the DIOPT
      diseases and traits query tool (DIOPT-DIST; http://www.flyrnai.org/diopt-dist).
      CONCLUSIONS: DIOPT and DIOPT-DIST are useful resources for researchers working
      with model organisms, especially those who are interested in exploiting model
      organisms such as Drosophila to study the functions of human disease genes.

PMID- 21880148
TI  - Integrating transcriptomics and metabonomics to unravel modes-of-action of
      2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in HepG2 cells.
AB  - BACKGROUND: The integration of different 'omics' technologies has already been
      shown in several in vivo studies to offer a complementary insight into cellular
      responses to toxic challenges. Being interested in developing in vitro cellular
      models as alternative to animal-based toxicity assays, we hypothesize that
      combining transcriptomics and metabonomics data improves the understanding of
      molecular mechanisms underlying the effects caused by a toxic compound also in
      vitro in human cells. To test this hypothesis, and with the focus on non
      genotoxic carcinogenesis as an endpoint of toxicity, in the present study, the
      human hepatocarcinoma cell line HepG2 was exposed to the well-known environmental
      carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). RESULTS: Transcriptomics
      as well as metabonomics analyses demonstrated changes in TCDD-exposed HepG2 in
      common metabolic processes, e.g. amino acid metabolism, of which some of the
      changes only being confirmed if both 'omics' were integrated. In particular, this
      integrated analysis identified unique pathway maps involved in receptor-mediated
      mechanisms, such as the G-protein coupled receptor protein (GPCR) signaling
      pathway maps, in which the significantly up-regulated gene son of sevenless 1
      (SOS1) seems to play an important role. SOS1 is an activator of several members
      of the RAS superfamily, a group of small GTPases known for their role in
      carcinogenesis. CONCLUSIONS: The results presented here were not only comparable
      with other in vitro studies but also with in vivo studies. Moreover, new insights
      on the molecular responses caused by TCDD exposure were gained by the cross-omics
      analysis.

PMID- 21880150
TI  - HYPEST study: profile of hypertensive patients in Estonia.
AB  - BACKGROUND: More than one third of adult population in Estonia has problems with
      elevated blood pressure (BP). The Hypertension in Estonia (HYPEST) study
      represents the country's first hypertension-targeted sample collection aiming to
      examine the epidemiological and genetic determinants for hypertension (HTN) and
      related cardiovascular diseases (CVD) in Estonian population. The HYPEST subjects
      (n = 1,966) were recruited across Estonia between 2004-2007 including clinically
      diagnosed HTN cases and population-based controls. The present report is focused
      on the clinical and epidemiological profile of HYPEST cases, and gender-specific
      effects on the pathophysiology of hypertension. METHODS: Current analysis was
      performed on 1,007 clinically diagnosed HTN patients (617 women and 390 men) aged
      18-85 years. The hypertensives were recruited to the study by BP specialists at
      the North Estonia Medical Center, Centre of Cardiology, Tallinn or at the
      Cardiology Clinic, Tartu University Hospital, Estonia. Longitudinal BP data was
      extracted retrospectively from clinical records. Current and retrospective data
      of patient's medical history, medication intake and lifestyle habits were derived
      from self-administrated questionnaire and each variable was examined separately
      for men and women. Eleven biochemical parameters were measured from fasting serum
      samples of 756 patients. RESULTS: The distribution of recruited men and women was
      39% and 61% respectively. Majority of Estonian HTN patients (85%) were overweight
      (BMI >= 25 kg/m2) and a total of 79% of patients had additional complications
      with cardiovascular system. In men, the hypertension started almost 5 years
      earlier than in women (40.5 +/- 14.5 vs 46.1 +/- 12.7 years), which led to
      earlier age of first myocardial infarction (MI) and overall higher incidence rate
      of MI among male patients (men 21.2%, women 8.9%, P < 0.0001). Heart arrhythmia,
      thyroid diseases, renal tubulo-intestinal diseases and hyperlipidemia were more
      prevalent in hypertensive women compared to men (P < 0.0001). An earlier age of
      HTN onset was significantly associated with smoking (P = 0.00007), obesity (BMI
      >= 30 kg/m2; P = 0.0003), increased stress (P = 0.0003) and alcohol consumption
      (P = 0.004). CONCLUSION: Understanding the clinical profile of HTN patients
      contributes to CVD management. Estonian hypertension patients exhibited different
      disease and risk profiles of male and female patients. This well-characterized
      sample set provides a good resource for studying hypertension and other
      cardiovascular phenotypes.

PMID- 21880149
TI  - Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell
      differentiation to a somatostatin/ghrelin co-expressing cell lineage.
AB  - BACKGROUND: Nkx2.2 and Arx represent key transcription factors implicated in the
      specification of islet cell subtypes during pancreas development. Mice deficient
      for Arx do not develop any alpha-cells whereas beta- and delta-cells are found in
      considerably higher numbers. In Nkx2.2 mutant animals, alpha- and beta-cell
      development is severely impaired whereas a ghrelin-expressing cell population is
      found augmented.Notably, Arx transcription is clearly enhanced in Nkx2.2
      deficient pancreata. Hence in order to precise the functional link between both
      factors we performed a comparative analysis of Nkx2.2/Arx single- and double
      mutants but also of Pax6-deficient animals. RESULTS: We show that most of the
      ghrelin+ cells emerging in pancreata of Nkx2.2- and Pax6-deficient mice, express
      the alpha-cell specifier Arx, but also additional beta-cell related genes. In
      Nkx2.2-deficient mice, Arx directly co-localizes with iAPP, PC1/3 and Pdx1
      suggesting an Nkx2.2-dependent control of Arx in committed beta-cells. The
      combined loss of Nkx2.2 and Arx likewise results in the formation of a
      hyperplastic ghrelin+ cell population at the expense of mature alpha- and beta
      cells. Surprisingly, such Nkx2.2-/-Arx- ghrelin+ cells also express the
      somatostatin hormone. CONCLUSIONS: Our data indicate that Nkx2.2 acts by
      reinforcing the transcriptional networks initiated by Pax4 and Arx in early
      committed beta- and alpha-cell, respectively. Our analysis also suggests that one
      of the coupled functions of Nkx2.2 and Pax4 is to counteract Arx gene activity in
      early committed beta-cells.

PMID- 21880151
TI  - Stability and change in health behaviours as predictors for disability pension: a
      prospective cohort study of Swedish twins.
AB  - BACKGROUND: Stability or changes of health behaviours have not been studied in
      association with incidence of disability pension (DP). The aims were to (1)
      investigate if stability or changes in health behaviours predict DP due to
      musculoskeletal diagnosis (MSD), (2) to evaluate if an association exists for DP
      in general, and (3) after taking familial confounding into account. METHODS: The
      study sample was 16,713 like-sexed twin individuals born in Sweden between 1935
      1958 (6195 complete twin pairs) who had participated in two surveys 25 years
      apart, were alive, and not pensioned at the time of the latest survey. Cox
      proportional hazards analysis was used to assess the associations (hazard ratios
      (HR) with 95% confidence intervals (CI)) between stability and change in health
      behaviours (physical activity, tobacco and alcohol use, body mass index (BMI)),
      and number of pain locations collected at two time points 25 years apart and the
      incidence of DP until 2008. RESULTS: During the follow-up, 1843 (11%) individuals
      were granted DP with 747 of these due to MSD. A higher proportion of women were
      granted DP than men. Increase in BMI and stable use of tobacco products were
      predictors for DP due to MSD (HR 1.21-1.48) and DP in general (HR 1.10-1.41). The
      stability in the frequency of physical activity and increased frequency of
      physical activity were protective factors for DP due to MSD only when accounting
      for familial confounding. However, the number of pain locations (stability,
      increase, or decrease) was the strongest predictor for future DP due to MSD (HR
      3.69, CI 2.99-4.56) and DP in general (HR 2.15, CI 1.92-2.42). In discordant pair
      analysis, the HRs for pain were lower, indicating potential familial confounding.
      CONCLUSIONS: Health behaviours in adulthood, including an increase in pain
      locations were associated with the incidence of DP. The association between
      physical activity and DP was especially related to adulthood choices or habits,
      i.e., the individual decision about frequency of exercising. Thus, it is
      important to e.g. increase public awareness of the potential beneficial effects
      of exercise throughout life to avoid permanent exclusion from the labour market
      for medical reasons.

PMID- 21880152
TI  - A eukaryotic-type signalling system of Pseudomonas aeruginosa contributes to
      oxidative stress resistance, intracellular survival and virulence.
AB  - BACKGROUND: The genome of Pseudomonas aeruginosa contains at least three genes
      encoding eukaryotic-type Ser/Thr protein kinases, one of which, ppkA, has been
      implicated in P. aeruginosa virulence. Together with the adjacent pppA
      phosphatase gene, they belong to the type VI secretion system (H1-T6SS) locus,
      which is important for bacterial pathogenesis. To determine the biological
      function of this protein pair, we prepared a pppA-ppkA double mutant and
      characterised its phenotype and transcriptomic profiles. RESULTS: Phenotypic
      studies revealed that the mutant grew slower than the wild-type strain in minimal
      media and exhibited reduced secretion of pyoverdine. In addition, the mutant had
      altered sensitivity to oxidative and hyperosmotic stress conditions.
      Consequently, mutant cells had an impaired ability to survive in murine
      macrophages and an attenuated virulence in the plant model of infection. Whole
      genome transcriptome analysis revealed that pppA-ppkA deletion affects the
      expression of oxidative stress-responsive genes, stationary phase sigma-factor
      RpoS-regulated genes, and quorum-sensing regulons. The transcriptome of the pppA
      ppkA mutant was also analysed under conditions of oxidative stress and showed an
      impaired response to the stress, manifested by a weaker induction of stress
      adaptation genes as well as the genes of the SOS regulon. In addition, expression
      of either RpoS-regulated genes or quorum-sensing-dependent genes was also
      affected. Complementation analysis confirmed that the transcription levels of the
      differentially expressed genes were specifically restored when the pppA and ppkA
      genes were expressed ectopically. CONCLUSIONS: Our results suggest that in
      addition to its crucial role in controlling the activity of P. aeruginosa H1-T6SS
      at the post-translational level, the PppA-PpkA pair also affects the
      transcription of stress-responsive genes. Based on these data, it is likely that
      the reduced virulence of the mutant strain results from an impaired ability to
      survive in the host due to the limited response to stress conditions.

PMID- 21880153
TI  - Plumbagin inhibits invasion and migration of breast and gastric cancer cells by
      downregulating the expression of chemokine receptor CXCR4.
AB  - BACKGROUND: Increasing evidence indicates that the interaction between the CXC
      chemokine receptor-4 (CXCR4) and its ligand CXCL12 is critical in the process of
      metastasis that accounts for more than 90% of cancer-related deaths. Thus, novel
      agents that can downregulate the CXCR4/CXCL12 axis have therapeutic potential in
      inhibiting cancer metastasis. METHODS: In this report, we investigated the
      potential of an agent, plumbagin (5-hydroxy-2-methyl-1, 4-naphthoquinone), for
      its ability to modulate CXCR4 expression and function in various tumor cells
      using Western blot analysis, DNA binding assay, transient transfection, real time
      PCR analysis, chromatin immunoprecipitation, and cellular migration and invasion
      assays. RESULTS: We found that plumbagin downregulated the expression of CXCR4 in
      breast cancer cells irrespective of their HER2 status. The decrease in CXCR4
      expression induced by plumbagin was not cell type-specific as the inhibition also
      occurred in gastric, lung, renal, oral, and hepatocellular tumor cell lines.
      Neither proteasome inhibition nor lysosomal stabilization had any effect on
      plumbagin-induced decrease in CXCR4 expression. Detailed study of the underlying
      molecular mechanism(s) revealed that the regulation of the downregulation of
      CXCR4 was at the transcriptional level, as indicated by downregulation of mRNA
      expression, inhibition of NF-kappaB activation, and suppression of chromatin
      immunoprecipitation activity. In addition, using a virtual, predictive,
      functional proteomics-based tumor pathway platform, we tested the hypothesis that
      NF-kappaB inhibition by plumbagin causes the decrease in CXCR4 and other
      metastatic genes. Suppression of CXCR4 expression by plumbagin was found to
      correlate with the inhibition of CXCL12-induced migration and invasion of both
      breast and gastric cancer cells. CONCLUSIONS: Overall, our results indicate, for
      the first time, that plumbagin is a novel blocker of CXCR4 expression and thus
      has the potential to suppress metastasis of cancer.

PMID- 21880154
TI  - Upregulation of microRNA-125b contributes to leukemogenesis and increases drug
      resistance in pediatric acute promyelocytic leukemia.
AB  - BACKGROUND: Although current chemotherapy regimens have remarkably improved the
      cure rate of pediatric acute promyelocytic leukemia (APL) over the past decade,
      more than 20% of patients still die of the disease, and the 5-year cumulative
      incidence of relapse is 17%. The precise gene pathways that exert critical
      control over the determination of cell lineage fate during the development of
      pediatric APL remain unclear. METHODS: In this study, we analyzed miR-125b
      expression in 169 pediatric acute myelogenous leukemia (AML) samples including 76
      APL samples before therapy and 38 APL samples after therapy. The effects of
      enforced expression of miR-125b were evaluated in leukemic cell and drug
      resistant cell lines. RESULTS: miR-125b is highly expressed in pediatric APL
      compared with other subtypes of AML and is correlated with treatment response, as
      well as relapse of pediatric APL. Our results further demonstrated that miR-125b
      could promote leukemic cell proliferation and inhibit cell apoptosis by
      regulating the expression of tumor suppressor BCL2-antagonist/killer 1 (Bak1).
      Remarkably, miR-125b was also found to be up-regulated in leukemic drug-resistant
      cells, and transfection of a miR-125b duplex into AML cells can increase their
      resistance to therapeutic drugs, CONCLUSIONS: These findings strongly indicate
      that miR-125b plays an important role in the development of pediatric APL at
      least partially mediated by repressing BAK1 protein expression and could be a
      potential therapeutic target for treating pediatric APL failure.

PMID- 21880156
TI  - Comparative decline in funding of European Commission malaria vaccine projects:
      what next for the European scientists working in this field?
AB  - Since 2000, under the Fifth and subsequent Framework Programmes, the European
      Commission has funded research to spur the development of a malaria vaccine. This
      funding has contributed to the promotion of an integrated infrastructure
      consisting of European basic, applied and clinical scientists in academia and
      small and medium enterprises, together with partners in Africa. Research has
      added basic understanding of what is required of a malaria vaccine, allowing
      selected candidates to be prioritized and some to be moved forward into clinical
      trials. To end the health burden of malaria, and its economic and social impact
      on development, the international community has now essentially committed itself
      to the eventual eradication of malaria. Given the current tentative advances
      towards elimination or eradication of malaria in many endemic areas, malaria
      vaccines constitute an additional and almost certainly essential component of any
      strategic plan to interrupt transmission of malaria. However, funding for malaria
      vaccines has been substantially reduced in the Seventh Framework Programme
      compared with earlier Framework Programmes, and without further support the gains
      made by earlier European investment will be lost.

PMID- 21880155
TI  - Tissue-specific gene expression templates for accurate molecular characterization
      of the normal physiological states of multiple human tissues with implication in
      development and cancer studies.
AB  - BACKGROUND: To elucidate the molecular complications in many complex diseases, we
      argue for the priority to construct a model representing the normal physiological
      state of a cell/tissue. RESULTS: By analyzing three independent microarray
      datasets on normal human tissues, we established a quantitative molecular model
      GET, which consists of 24 tissue-specific Gene Expression Templates constructed
      from a set of 56 genes, for predicting 24 distinct tissue types under disease
      free condition. 99.2% correctness was reached when a large-scale validation was
      performed on 61 new datasets to test the tissue-prediction power of GET. Network
      analysis based on molecular interactions suggests a potential role of these 56
      genes in tissue differentiation and carcinogenesis.Applying GET to transcriptomic
      datasets produced from tissue development studies the results correlated well
      with developmental stages. Cancerous tissues and cell lines yielded significantly
      lower correlation with GET than the normal tissues. GET distinguished melanoma
      from normal skin tissue or benign skin tumor with 96% sensitivity and 89%
      specificity. CONCLUSIONS: These results strongly suggest that a normal tissue or
      cell may uphold its normal functioning and morphology by maintaining specific
      chemical stoichiometry among genes. The state of stoichiometry can be depicted by
      a compact set of representative genes such as the 56 genes obtained here. A
      significant deviation from normal stoichiometry may result in malfunction or
      abnormal growth of the cells.

PMID- 21880157
TI  - Development of a serotype colloidal gold strip using monoclonal antibody for
      rapid detection type Asia1 foot-and-mouth disease.
AB  - BACKGROUND: In this study, we developed a rapid, one step colloid gold strip
      (CGS) capable of specifically detecting type Asia1 foot-and-mouth disease virus
      (FMDV). We have produced two monoclonal antibodies (mAb) to type Asia1 FMD (named
      1B8 and 5E2). On the test strip, the purified 1B8 labelled with the colloidal
      gold was used as the detector, and the purified 5E2 and goat anti-mouse
      antibodies were wrapped onto nitrocellulose (NC) membranes as the test and the
      control line, respectively. The rapid colloidal gold stereotype diagnostic strip
      was housed in a plastic case. RESULTS: In specificity and sensitivity assay,
      there was no cross-reaction of the antigen with the other type of FMD and SVDV.
      The detection sensitivity was found to be as high as 10(-5) dilution of
      Asia1/JSL/05 (1 * 10(7.2)TCID(50)/50 MUL). There was excellent agreement between
      the results obtained by CGS and reverse indirect hemagglutination assay (RIHA),
      and the agreement can reach to 98.75%. CONCLUSION: We developed colloidal gold
      strips that have good qualities and does not require specialized equipment or
      technicians. This method provided a feasible, convenient, rapid, and effective
      for detecting type Asia1 FMDV in the fields.

PMID- 21880159
TI  - Is sex necessary?
AB  - Fungal sexual reproductive modes have markedly high diversity and plasticity, and
      asexual species have been hypothesized to arise frequently from sexual fungal
      species. A recent study on the red yeasts provides further support for the notion
      that sexual ancestors may give rise to shorter-lived asexual species. However,
      presumed asexual species may also be cryptically sexual, as revealed by other
      recent studies.

PMID- 21880158
TI  - A cost comparison of electronic and hybrid data collection systems in Ontario
      during pandemic and seasonal influenza vaccination campaigns.
AB  - BACKGROUND: During the pandemic (H1N1) 2009 influenza vaccination campaign,
      health regions in Canada collected client-level immunization data using fully
      electronic or hybrid systems, with the latter comprising both electronic and
      paper-based elements. The objective of our evaluation was to compare projected
      five-year costs associated with implementing these systems in Ontario public
      health units (PHUs) during pandemic and seasonal influenza vaccination campaigns.
      METHODS: Six PHUs provided equipment and staffing costs during the pandemic
      (H1N1) 2009 influenza vaccination campaign and staffing algorithms for seasonal
      campaigns. We standardized resources to population sizes 100,000, 500,000 and
      1,000,000, assuming equipment lifetime of five years and public health vaccine
      administration rates of 18% and 2.5% for H1N1 and seasonal campaigns,
      respectively. Two scenarios were considered: Year 1 pandemic and Year 1 seasonal
      campaigns, each followed by four regular influenza seasons. Costs were discounted
      at 5%. RESULTS: Assuming a Year 1 pandemic, the five-year costs per capita for
      the electronic system decrease as PHU population size increases, becoming
      increasingly less costly than hybrid systems ($4.33 vs. $4.34 [100,000], $4.17
      vs. $4.34 [500,000], $4.12 vs. $4.34 [1,000, 000]). The same trend is observed
      for the scenario reflecting five seasonal campaigns, with the electronic system
      being less expensive per capita than the hybrid system for all population sizes
      ($1.93 vs. $1.95 [100,000], $1.91 vs. $1.94 [500,000], $1.87 vs. $1.94 [1,000,
      000]). Sensitivity analyses identified factors related to nurse hours as
      affecting the direction and magnitude of the results. CONCLUSIONS: Five-year cost
      projections for electronic systems were comparable or less expensive than for
      hybrid systems, at all PHU population sizes. An intangible benefit of the
      electronic system is having data rapidly available for reporting.

PMID- 21880160
TI  - Origins of cellular geometry.
AB  - Cells are highly complex and orderly machines, with defined shapes and a
      startling variety of internal organizations. Complex geometry is a feature of
      both free-living unicellular organisms and cells inside multicellular animals.
      Where does the geometry of a cell come from? Many of the same questions that
      arise in developmental biology can also be asked of cells, but in most cases we
      do not know the answers. How much of cellular organization is dictated by global
      cell polarity cues as opposed to local interactions between cellular components?
      Does cellular structure persist across cell generations? What is the relationship
      between cell geometry and tissue organization? What ensures that intracellular
      structures are scaled to the overall size of the cell? Cell biology is only now
      beginning to come to grips with these questions.

PMID- 21880161
TI  - Nucleic acid transfection and transgenesis in parasitic nematodes.
AB  - Transgenesis is an essential tool for assessing gene function in any organism,
      and it is especially crucial for parasitic nematodes given the dwindling
      armamentarium of effective anthelmintics and the consequent need to validate
      essential molecular targets for new drugs and vaccines. Two of the major routes
      of gene delivery evaluated to date in parasitic nematodes, bombardment with DNA
      coated microparticles and intragonadal microinjection of DNA constructs, draw
      upon experience with the free-living nematode Caenorhabditis elegans. Bombardment
      has been used to transiently transfect Ascaris suum, Brugia malayi and
      Litomosoides sigmodontis with both RNA and DNA. Microinjection has been used to
      achieve heritable transgenesis in Strongyloides stercoralis, S. ratti and
      Parastrongyloides trichosuri and for additional transient expression studies in
      B. malayi. A third route of gene delivery revisits a classic method involving DNA
      transfer facilitated by calcium-mediated permeabilization of recipient cells in
      developing B. malayi larvae and results in transgene inheritance through host and
      vector passage. Assembly of microinjected transgenes into multi-copy episomal
      arrays likely results in their transcriptional silencing in some parasitic
      nematodes. Methods such as transposon-mediated transgenesis that favour low-copy
      number chromosomal integration may remedy this impediment to establishing stable
      transgenic lines. In the future, stable transgenesis in parasitic nematodes could
      enable loss-of-function approaches by insertional mutagenesis, in situ expression
      of inhibitory double-stranded RNA or boosting RNAi susceptibility through
      heterologous expression of dsRNA processing and transport proteins.

PMID- 21880163
TI  - Infant nutrition and allergy.
AB  - Over the past several decades, the incidence of atopic diseases such as asthma,
      atopic dermatitis and food allergies has increased dramatically. Although atopic
      diseases have a clear genetic basis, environmental factors, including early
      infant nutrition, may have an important influence on their development.
      Therefore, attempts have been made to reduce the risk of the development of
      allergy using dietary modifications, mainly focused on longer breast-feeding and
      delayed introduction or elimination of foods identified as potentially most
      allergenic. Recently, there is also an increasing interest in the active
      prevention of atopy using specific dietary components. Many studies have shown
      that breast-feeding may have the protective effect against future atopic
      dermatitis and early childhood wheezing. Concerning complementary feeding, there
      is evidence that the introduction of complementary foods before 4 months of age
      may increase the risk for atopic dermatitis. However, there is no current
      convincing evidence that delaying introduction of solids after 6 months of age
      has a significant protective effect on the development of atopic disease
      regardless of whether infants are fed cow's milk protein formula or human
      subject's milk, and this includes delaying the introduction of foods that are
      considered to be highly allergic, such as fish, eggs and foods containing peanut
      protein. In conclusion, as early nutrition may have profound implications for
      long-term health and atopy later in life, it presents an opportunity to prevent
      or delay the onset of atopic diseases.

PMID- 21880162
TI  - The consequences of obesity and excess weight gain in pregnancy.
AB  - The prevalence of obesity in pregnancy is rising exponentially; about 15-20% of
      pregnant women now enter pregnancy with a BMI which would define them as obese.
      This paper provides a review of the strong links between obesity and adverse
      pregnancy outcome which operate across a range of pregnancy complications. For
      example, obesity is associated with an increased risk of maternal mortality,
      gestational diabetes mellitus, thromboembolism, pre-eclampsia and postpartum
      haemorrhage. Obesity also complicates operative delivery; it makes operative
      delivery more difficult, increases complications and paradoxically increases the
      need for operative delivery. The risk of the majority of these complications is
      amplified by excess weight gain in pregnancy and increases in proportion to the
      degree of obesity, for example, women with extreme obesity have OR of 7.89 for
      gestational diabetes and 3.84 for postpartum haemorrhage compared to their lean
      counterparts. The consequences of maternal obesity do not stop once the baby is
      born. Maternal obesity programmes a variety of long-term adverse outcomes,
      including obesity in the offspring at adulthood. Such an effect is mediated at
      least in part via high birthweight; a recent study has suggested that the odds of
      adult obesity are two-fold greater in babies weighing more than 4 kg at birth.
      The mechanism by which obesity causes adverse pregnancy outcome is uncertain.
      This paper reviews the emerging evidence that hyperglycaemia and insulin
      resistance may both play a role: the links between hyperglycaemia in pregnancy
      and both increased birthweight and insulin resistance have been demonstrated in
      two large studies. Lastly, we discuss the nature and rationale for possible
      intervention strategies in obese pregnant women.

PMID- 21880164
TI  - Maternal and child obesity: some policy challenges.
AB  - The recent rise in the prevalence of obesity in the UK population includes women
      of reproductive age and children. For both groups there are specific health
      concerns consequent on excess bodyweight, including obstetric complications,
      fetal growth abnormalities and a range of obesity co-morbidities seen in children
      that were rarely found in young people a generation earlier. This paper
      identifies some of the issues which challenge policy-makers: guidelines for
      gestational weight gain and for weight loss after pregnancy; inequalities and
      interventions in pregnancy; interventions to prevent child obesity; and the role
      of individuals, government and the commercial sector in implementing policies for
      promoting healthy weight.

PMID- 21880165
TI  - Insecure attachment and frequent attendance in primary care: a longitudinal
      cohort study of medically unexplained symptom presentations in ten UK general
      practices.
AB  - BACKGROUND: In primary care frequent attenders with medically unexplained
      symptoms (MUS) pose a clinical and health resource challenge. We sought to
      understand these presentations in terms of the doctor-patient relationship,
      specifically to test the hypothesis that such patients have insecure emotional
      attachment. METHOD: We undertook a cohort follow-up study of 410 patients with
      MUS. Baseline questionnaires assessed adult attachment style, psychological
      distress, beliefs about the symptom, non-specific somatic symptoms, and physical
      function. A telephone interview following consultation assessed health worry,
      general practitioner (GP) management and satisfaction with consultation. The main
      outcome was annual GP consultation rate. RESULTS: Of consecutive attenders, 18%
      had an MUS. This group had a high mean consultation frequency of 5.24 [95%
      confidence interval (CI) 4.79-5.69] over the follow-up year. The prevalence of
      insecure attachment was 28 (95% CI 23-33) %. A significant association was found
      between insecure attachment style and frequent attendance, even after adjustment
      for sociodemographic characteristics, presence of chronic physical illness and
      baseline physical function [odds ratio (OR) 1.96 (95% CI 1.05-3.67)]. The
      association was particularly strong in those patients who believed that there was
      a physical cause for their initial MUS [OR 9.52 (95% CI 2.67-33.93)]. A possible
      model for the relationship between attachment style and frequent attendance is
      presented. CONCLUSIONS: Patients with MUS who attend frequently have insecure
      adult attachment styles, and their high consultation rate may therefore be
      conceptualized as pathological care-seeking behaviour linked to their insecure
      attachment. Understanding frequent attendance as pathological help seeking driven
      by difficulties in relating to caregiving figures may help doctors to manage
      their frequently attending patients in a different way.

PMID- 21880166
TI  - Projections from cingulate cortex to the cat's thalamic reticular nucleus.
AB  - The cingulate cortex (CG) and the adjacent region designated as the splenial
      visual area (SVA) project to areas of the extrageniculate thalamic system that
      are concerned with processing visual information. En route to the thalamus, they
      pass through the thalamic reticular nucleus (TRN), an important source of
      thalamic inhibition. We wished to determine whether SVA axon collaterals
      projected to the previously defined visual sector of the TRN or a separate
      projection zone and did this differ from the projection zone of CG. We
      iontophoretically injected different neuroanatomical tracers into several
      locations within CG/SVA and traced the labeled axons through the TRN. The CG and
      SVA have a projection zone that only partially overlaps the dorsorostral regions
      of the visuocortical projection zone; there was no evidence to suggest separate
      SVA and CG zones or tiers of label within the TRN. The projection formed only a
      weak topographic map in the TRN, which is largely defined in the rostrocaudal
      axis and is similar to that of the area 7 projection; both projections have a
      high degree of overlap in the dorsal TRN. We postulate that CG/SVA may be
      involved in the initiation of orientation behaviors via stimulation of thalamic
      nuclei and attentional mechanisms of the TRN.

PMID- 21880167
TI  - The vulnerable child.

PMID- 21880168
TI  - Prevalence of smear-positive tuberculosis in persons aged >= 15 years in
      Bangladesh: results from a national survey, 2007-2009.
AB  - The aim of this study was to determine the nationwide prevalence of smear
      positive tuberculosis (TB) in Bangladesh. A multi-stage cluster survey of a
      random sample of persons aged >= 15 years was included in 40 clusters (20 urban,
      20 rural). Two sputum samples were collected from study participants and tested
      initially by fluorescence microscopy and confirmed by the Ziehl-Neelsen method.
      The crude and adjusted prevalence rates and 95% confidence intervals (CIs) were
      calculated using standard methods. A total of 33 new smear-positive TB cases were
      detected among 52 098 individuals who participated in the study. The average
      participation rate was over 80%. The overall crude prevalence of new smear
      positive TB in persons aged >= 15 years was estimated as 63.3/100 000 (95% CI
      43.6-88.9) and the adjusted prevalence was 79.4/100 000 (95% CI 47.1-133.8). TB
      prevalence was higher in males (n = 24) and in rural areas (n = 20). The
      prevalence was highest in the 55-64 years age group (201/100 000) and lowest in
      15-24 years age group (43.0/100 000). The prevalence was higher in persons with
      no education (138.6/100 000, 95% CI 78.4-245.0). The overall prevalence of smear
      positive TB was significantly lower than the prevalence estimate of the previous
      nationwide survey in Bangladesh in 1987-1988 (870/100 000).

PMID- 21880169
TI  - The influence of depression on processing speed and executive function in
      nondemented subjects aged 75.
AB  - Neuropsychological deficits are commonly found to be part of depression in old
      age and might simultaneously represent early symptoms of dementia. We
      investigated the influence of depression on processing speed and executive
      function in subjects who did not develop dementia during the following 5 years to
      examine whether these neuropsychological dysfunctions are due to depression or
      are influenced by other causes (e.g., education, cerebral comorbidity). A total
      of 287 subjects aged 75 (mean: 75.76) were available for analyses. Processing
      speed was measured by the Trail Making Test-A, Executive Function by the Trail
      Making Test-B and Verbal Fluency. DSM-IV-criteria were used for diagnosing
      depression. Cerebral comorbidity (e.g., stroke, Parkinson's disease), sex,
      education, antidepressant, and/or benzodiazepine medication, and a history of
      depression were taken into account as covariates. Univariate analyses and
      multiple regression analyses were calculated. Higher education was strongly
      related to better performance in all three psychometric tests. Cerebral
      comorbidity significantly slowed TMT-A performance and reduced Verbal Fluency
      scores. In multiple regression analysis depression showed only a minor, slowing
      influence on TMT-A and TMT-B performance. Depression only had a minor influence
      on processing speed and executive function in this sample of nondemented
      subjects. By comparison, the influence of education and cerebral comorbidity was
      seen to be stronger.

PMID- 21880170
TI  - Performance-based everyday functioning after stroke: relationship with IADL
      questionnaire and neurocognitive performance.
AB  - Neuropsychologists frequently are asked to comment on everyday functioning, but
      the research relies mostly on questionnaire-based assessment of daily
      functioning. While performance-based assessment of everyday functioning has many
      advantages over commonly used questionnaires, there are few empirically validated
      comprehensive performance-based measures. We present data here on a performance
      based battery of daily living skills, the Functional Impact Assessment (FIA) in
      47 unilateral stroke patients and 37 matched healthy controls. The FIA was
      validated by comparing it to performance on the self- and informant-report
      version of the Functional Activities Questionnaire (FAQ). We also examined the
      relationship between the FIA and cognitive functioning using the
      Neuropsychological Assessment Battery (NAB). The stroke group's performance on
      the FIA, FAQ (self and informant), and NAB (total and domain scores) was
      significantly (d's >= .80) lower than the control group. The NAB total score and
      all domain scores were highly correlated with the FIA in the stroke group (r's >
      .7), and only one NAB domain score (visuospatial) was a unique predictor. This
      may be due to the fact that most of the NAB domains have a statistical problem of
      multicollinearity, which may explain why only the spatial domain was a unique
      predictor. While the informant FAQ was significantly correlated with FIA total
      score (r = .48, p < .01), the NAB total score was a significantly better
      predictor (r = .83, p < .001) than the informant FAQ. NAB total scaled score of
      less than 86 predicted impairment on the FIA with 92% sensitivity and 84%
      specificity. Our findings argue that the FIA is sensitive to deficits associated
      with stroke and is highly associated with all neuropsychological domains
      (attention, executive functions, language and spatial skills, and memory).

PMID- 21880171
TI  - Verbal serial list learning in mild cognitive impairment: a profile analysis of
      interference, forgetting, and errors.
AB  - Using cluster analysis Libon et al. (2010) found three verbal serial list
      learning profiles involving delay memory test performance in patients with mild
      cognitive impairment (MCI). Amnesic MCI (aMCI) patients presented with low scores
      on delay free recall and recognition tests; mixed MCI (mxMCI) patients scored
      higher on recognition compared to delay free recall tests; and dysexecutive MCI
      (dMCI) patients generated relatively intact scores on both delay test conditions.
      The aim of the current research was to further characterize memory impairment in
      MCI by examining forgetting/savings, interference from a competing word list,
      intrusion errors/perseverations, intrusion word frequency, and recognition foils
      in these three statistically determined MCI groups compared to normal control
      (NC) participants. The aMCI patients exhibited little savings, generated more
      highly prototypic intrusion errors, and displayed indiscriminate responding to
      delayed recognition foils. The mxMCI patients exhibited higher saving scores,
      fewer and less prototypic intrusion errors, and selectively endorsed recognition
      foils from the interference list. dMCI patients also selectively endorsed
      recognition foils from the interference list but performed similarly compared to
      NC participants. These data suggest the existence of distinct memory impairments
      in MCI and caution against the routine use of a single memory test score to
      operationally define MCI.

PMID- 21880172
TI  - Functional magnetic resonance imaging of working memory reveals frontal
      hypoactivation in middle-aged adults with cognitive complaints.
AB  - Older adults with cardiovascular disease (CVD) often complain about cognitive
      difficulties including reduced processing speed and attention. On cross-sectional
      examination, such reports relate more closely to mood than to cognitive
      performance; yet, in longitudinal studies, these complaints have foreshadowed
      cognitive decline over time. To test the hypothesis that self-reported cognitive
      difficulties reflect early changes in brain function, we examined cognitive
      complaints and depression in relation to blood oxygen level dependent (BOLD)
      response to a cognitive task in middle-aged adults at risk for CVD. Forty-nine
      adults (ages 40 to 60 years) completed a measure of perceived cognitive
      dysfunction (Cognitive Difficulties Scale), medical history questionnaire,
      neuropsychological assessment and functional magnetic resonance imaging (fMRI)
      during a working memory task. Increased report of cognitive difficulties was
      significantly associated with weaker task-related activation in the right
      superior frontal/ middle frontal gyrus (F(4,44) = 3.26; p = .020, CDS beta = 
      0.39; p = .009) and the right inferior frontal gyrus (F(4,44) = 3.14; p = .024,
      CDS beta = -0.45; p = .003), independent of age, education, and self-reported
      depressive symptoms. Lower activation intensity in the right superior frontal
      gyrus was related to trends toward poorer task performance. Thus, self-reported
      cognitive difficulties among cognitively normal middle-aged adults may provide
      important clinical information about early brain vulnerability that should be
      carefully monitored.

PMID- 21880173
TI  - Effect of literacy and education on the visuoconstructional ability of non
      demented elderly individuals.
AB  - Learning to read and to write influences not only verbal skills but also global
      cognitive performance. Our study aimed to compare the visuoconstructional
      abilities of elderly illiterates with those of elderly literates. A total of 125
      healthy subjects over 65 years old were recruited. Korean version of Mini-Mental
      State Examination (K-MMSE) and the Alzheimer's Disease Assessment Scale-cognitive
      subscale (ADAS-cog) constructional praxis examination were used. We divided
      subjects into three groups (educated literate n = 53, uneducated literate n = 36
      and uneducated illiterate n = 36). Interlocking pentagons drawing, a part of the
      K-MMSE, was scored using the 6-point hierarchical scale. The uneducated
      illiterate group obtained significantly lower scores than did the other two
      groups. Scores on the ADAS-cog constructional praxis test were highest in the
      educated-literate group and those in the uneducated-illiterate group obtained the
      lowest scores. We demonstrated that illiteracy influences not only language
      performance but also visuoconstructional functioning.

PMID- 21880174
TI  - Somatic cytochrome c (CYCS) gene expression and promoter-specific DNA methylation
      in a porcine model of prenatal exposure to maternal dietary protein excess and
      restriction.
AB  - There is growing evidence that maternal nutrition during gestation has an
      important effect on offspring development as well as on their gene expression
      with long-term effects on the metabolic state. A potential mechanism forming long
      lasting gene expression patterns is DNA methylation of cytosine in CpG
      dinucleotides within the promoter region of distinct genes. There has been
      special focus on mitochondrial dysfunction by prenatal malnourishment over the
      recent years. To this end, we investigated the gene expression of somatic
      cytochrome c (CYCS), an important member of the respiratory chain, in a porcine
      model of gestational protein over- and undersupply at 94 d post-conception and 1,
      28 and 188 d of age, and analysed the association with the DNA methylation status
      within the CYCS promoter. Gene expression on day 1 post natum showed a
      significant increase in the low protein (LP) group (P = 0.0005) and a slight
      increase in the high protein (HP) group (P = 0.079) compared with the control
      (CO) group in the liver. The mean of the methylation level over forty-seven CpG
      sites from nucleotide (nt) - 417 to - 10 was significantly decreased in the LP (P
      = 0.007) and HP (P = 0.009) groups compared with that in the CO group. Excess and
      restricted protein supply during pregnancy led to hypomethylation of a number of
      CpG sites in the CYCS promoter, including those representing putative
      transcription factor-binding sites, associated with elevated expression levels.
      However, the impact of the low-protein gestation diet is more pronounced,
      indicating that the offspring could better adapt to excess rather than restricted
      protein supply.

PMID- 21880176
TI  - Self-care management and risk factors for depressive symptoms among elderly
      outpatients in Taiwan.
AB  - BACKGROUND: Early detection and appropriate treatment interventions for
      depressive symptoms in the elderly are important issues for healthcare systems.
      However, few studies to date have focused on understanding self-care strategies
      to manage depressive symptoms among elderly people worldwide. The purpose of this
      study was to explore self-care management strategies and risk factors for
      depressive symptoms among elderly outpatients in Taiwan. METHODS: A convenience
      sample of elderly persons (>=65 years old; N = 1054) was recruited from
      outpatient clinics of two hospitals in northern Taiwan. RESULTS: In our sample,
      the prevalence of depressive tendency was 16.3%. The majority of participants
      (70.1%) managed depressive symptoms with self-care strategies. The strategy most
      often used to relieve depressive symptoms was "take a walk." The main information
      source for self-care strategies was self-learning. Depressive tendency in this
      sample was shown by logistic regression analysis to be significantly predicted by
      gender, marital status, perceived income adequacy, perceived health condition,
      stroke, and cancer. CONCLUSION: Elderly people need to be made more aware of
      strategies to self-manage depressive symptoms. Healthcare providers can
      decrease/prevent the first risk factor for depressive symptoms (poor perceived
      health status) by improving elders' perceived health and promoting their actual
      health. The second risk factor (poor perceived income adequacy) can be
      decreased/prevented by carefully assessing patients' financial situation during
      clinic visits and providing suitable referral for further assistance.

PMID- 21880175
TI  - Identifying target groups for the prevention of depression among caregivers of
      dementia patients.
AB  - BACKGROUND: Depression in informal caregivers of persons with dementia is a
      major, costly and growing problem. However, it is not yet clear which caregivers
      are at increased risk of developing depression. With this knowledge preventive
      strategies could focus on these groups to maximize health gain and minimize
      effort. METHODS: The onset of clinically relevant depression was measured with
      the Center for Epidemiologic Studies - Depression Scale in 725 caregivers who
      were not depressed at baseline and who were providing care for a relative with
      dementia. Caregivers were followed over 18 months. The indices calculated to
      identify the most important risk indicators were: odds ratio, attributable
      fraction, exposure rate and number needing to be treated. RESULTS: The following
      significant indicators of depression onset were identified: increased initial
      depressive symptoms, poor self-rated health status and white or Hispanic
      race/ethnicity. The incidence of depression would decrease by 72.3% (attributive
      fraction) if these risk indicators together are targeted by a completely
      effective intervention. Race/ethnicity was not a significant predictor if
      caregivers of patients who died or were institutionalized were left out of the
      analyses. CONCLUSION: Detection of only a few characteristics makes it possible
      to identify high-risk groups in an efficient way. Focusing on these easy-to
      assess characteristics might contribute to a cost-effective prevention of
      depression in caregivers.

PMID- 21880177
TI  - Delivering safeguarding children services in primary care: responding to national
      child protection policy.
AB  - AIM: This study set out to examine how Primary Care Organisations (PCOs) in
      England manage, organise and deliver their safeguarding children
      responsibilities. BACKGROUND: In the light of changing organisational
      configurations across primary care, a wealth of policy directives and a climate
      of extensive media attention around child protection, this paper focuses on how
      PCOs respond to national policy and deliver safeguarding children services.
      METHOD: This study, based in England, United Kingdom (UK), used a telephone
      survey method incorporating semi-structured qualitative interviews with
      Designated Child Protection Nurses. A maximum variation sampling strategy was
      used to identify two to three PCOs within each of the original 28 Strategic
      Health Authority sites. From the 64 PCOs approached, 60 Designated Nurses or
      their representatives agreed to participate in the research, with a response rate
      of 94%. Data analysis was informed primarily by Lincoln and Guba's (1985) three
      stages of a) unitising, b) categorising and c) pattern search. FINDINGS: The
      findings outline how and to what extent PCOs respond to the national policy and
      organise and deliver their child protection services. The paper highlights some
      of the key challenges facing PCOs, in particular, safeguarding moving off the
      primary care agenda, child protection staff recruitment difficulties, a
      proliferation and overload of policy, resource implications for additional staff
      training, challenges to collaborative working, high referral thresholds to social
      care services and cutbacks in public health nursing services. This paper
      concludes by offering some suggestions about how child protection services could
      be improved as primary care faces another major reorganisation with the demise of
      Primary Care Trusts in April 2013.

PMID- 21880178
TI  - Platelet-derived growth factor signaling in human malignancies.
AB  - Platelet-derived growth factors (PDGFs) and their receptors were identified and
      purified decades ago. PDGFs are important during normal development and in human
      cancers. In particular, autocrine PDGF signaling has been implicated in various
      types of malignancies such as gliomas and leukemia. In contrast, paracrine
      signaling was found in cancers that originate from epithelial cells, where it may
      be involved in stromal cell recruitment, metastasis, and epithelial-mesenchymal
      transition. This editorial briefly discusses autocrine and paracrine PDGF
      signaling and their roles in human cancers, and introduces a series of review
      articles in this issue that address the possible roles of PDGFs in various
      processes involved in different types of cancers.

PMID- 21880179
TI  - Serglycin in human cancers.
AB  - Serglycin belongs to a family of small proteoglycans with Ser-Gly dipeptide
      repeats, and it is modified with different types of glycosaminoglycan side
      chains. Intracellular serglycin affects the retention and secretion of proteases,
      chemokines, or other cytokines by physically binding to these factors in
      secretory granules. Extracellular serglycin has been found to be released by
      several types of human cancer cells, and it is able to promote the metastasis of
      nasopharyngeal carcinoma cells. Serglycin can bind to CD44, which is another
      glycoprotein located in cellular membrane. Serglycin's function of promoting
      cancer cell metastasis depends on glycosylation of its core protein, which can be
      achieved by autocrine as well as paracrine secretion mechanisms. Further
      investigations are warranted to elucidate serglycin signaling mechanisms with the
      goal of targeting them to prevent cancer cell metastasis.

PMID- 21880181
TI  - Epithelial-mesenchymal transition in breast cancer progression and metastasis.
AB  - Breast cancer is the most common cancer in women, and approximately 90% of breast
      cancer deaths are caused by local invasion and distant metastasis of tumor cells.
      Epithelial-mesenchymal transition (EMT) is a vital process for large-scale cell
      movement during morphogenesis at the time of embryonic development. Tumor cells
      usurp this developmental program to execute the multi-step process of
      tumorigenesis and metastasis. Several transcription factors and signals are
      involved in these events. In this review, we summarize recent advances in breast
      cancer researches that have provided new insights in the molecular mechanisms
      underlying EMT regulation during breast cancer progression and metastasis. We
      especially focus on the molecular pathways that control EMT.

PMID- 21880182
TI  - Implication of platelet-derived growth factor receptor alpha in prostate cancer
      skeletal metastasis.
AB  - Metastasis represents by far the most feared complication of prostate carcinoma
      and is the main cause of death for patients. The skeleton is frequently targeted
      by disseminated cancer cells and represents the sole site of spread in more than
      80% of prostate cancer cases. Compatibility between select malignant phenotypes
      and the microenvironment of colonized tissues is broadly recognized as the
      culprit for the organ-tropism of cancer cells. Here, we review our recent studies
      showing that the expression of platelet-derived growth factor receptor alpha
      (PDGFRalpha) supports the survival and growth of prostate cancer cells in the
      skeleton and that the soluble fraction of bone marrow activates PDGFRalpha in a
      ligand-independent fashion. Finally, we offer pre-clinical evidence that this
      receptor is a viable target for therapy.

PMID- 21880180
TI  - Platelet-derived growth factor receptor alpha in glioma: a bad seed.
AB  - Recent collaborative, large-scale genomic profiling of the most common and
      aggressive brain tumor glioblastoma multiforme(GBM) has significantly advanced
      our understanding of this disease. The gene encoding platelet-derived growth
      factor receptor alpha(PDGFRalpha) was identified as the third of the top 11
      amplified genes in clinical GBM specimens. The important roles of PDGFRalpha
      signaling during normal brain development also implicate the possible pathologic
      consequences of PDGFRalpha over-activation in glioma. Although the initial
      clinical trials using PDGFR kinase inhibitors have been predominantly
      disappointing, diagnostic and treatment modalities involving genomic profiling
      and personalized medicine are expected to improve the therapy targeting
      PDGFRalpha signaling. In this review, we discuss the roles of PDGFRalphasignaling
      during development of the normal central nervous system(CNS) and in pathologic
      conditions such as malignant glioma. We further compare various animal models of
      PDGF-induced gliomagenesis and their potential as a novel platform of pre
      clinical drug testing. We then summarize our recent publication and how these
      findings will likely impact treatments for gliomas driven by PDGFRalpha
      overexpression. A better understanding of PDGFRalpha signaling in glioma and
      their microenvironment, through the use of human or mouse models, is necessary to
      design a more effective therapeutic strategy against gliomas harboring the
      aberrant PDGFRalpha signaling.

PMID- 21880183
TI  - A single nucleotide polymorphism in the matrix metalloproteinase 2 promoter is
      closely associated with high risk of nasopharyngeal carcinoma in Cantonese from
      southern China.
AB  - Matrix metalloproteinase 2 (MMP2) has been shown to play an important role in
      several steps of cancer development. The -1306C/T polymorphism of the MMP2 gene
      displays a strikingly lower promoter activity than the T allele, and the CC
      genotype in the MMP2 promoter has been reported to associate with the development
      of several cancers. To assess the contribution of the MMP2 -1306C/T polymorphism
      to the risk of nasopharyngeal carcinoma (NPC), we conducted a case-control study
      and analyzed MMP2 genotypes in 370 patients with NPC and 390 frequency-matched
      controls using real-time PCR-based TaqMan allele analysis. We found that subjects
      with the CC genotype had an increased risk (OR = 1.55, 95% CI = 1.05-2.27) of
      developing NPC compared to those with the CT or TT genotypes. Furthermore, we
      found that the risk of NPC was markedly increased in subjects who were smokers
      (OR = 15.04, 95% CI = 6.65-33.99), heavy smokers who smoked >= 20 pack-years (OR
      = 18.66, 95% CI = 7.67-45.38), or young (<60 years) at diagnosis (OR = 1.52, 95%
      CI = 1.01-2.29). Our results provide molecular epidemiological evidence that the
      MMP2 -1306C/T promoter polymorphism is associated with NPC risk, and this
      association is especially noteworthy in heavy smokers.

PMID- 21880184
TI  - Overexpression of centromere protein H is significantly associated with breast
      cancer progression and overall patient survival.
AB  - Breast cancer is one of the leading causes of cancer death worldwide. This study
      aimed to analyze the expression of centromere protein H (CENP-H) in breast cancer
      and to correlate it with clinicopathologic data, including patient survival.
      Using reverse transcription-polymerase chain reaction and Western blotting to
      detect the expression of CENP-H in normal mammary epithelial cells, immortalized
      mammary epithelial cell lines, and breast cancer cell lines, we observed that the
      mRNA and protein levels of CENP-H were higher in breast cancer cell lines and in
      immortalized mammary epithelial cells than in normal mammary epithelial cells. We
      next examined CENP-H expression in 307 paraffin-embedded archived samples of
      clinicopathologically characterized breast cancer using immunohistochemistry, and
      detected high CENP-H expression in 134 (43.6%) samples. Statistical analysis
      showed that CENP-H expression was related with clinical stage (P = 0.001), T
      classification (P = 0.032), N classification (P = 0.018), and Ki-67 (P < 0.001).
      Patients with high CENP-H expression had short overall survival. Multivariate
      analysis showed that CENP-H expression was an independent prognostic indicator
      for patient survival. Our results suggest that CENP-H protein is a valuable
      marker of breast cancer progression and prognosis.

PMID- 21880185
TI  - Ubc9 expression predicts chemoresistance in breast cancer.
AB  - Ubiquitin-conjugating enzyme 9 (Ubc9), the sole conjugating enzyme for
      sumoylation, regulates protein function and plays an important role in
      tumorigenesis. Whether Ubc9 is involved in the chemoresistance of breast cancer
      remains unknown. In this study, we aimed to evaluate the contribution of Ubc9 in
      the chemoresistance of breast cancer. Immunohistochemistry (IHC) was used to
      examine the expression level of Ubc9. Chi-square test, Wilcoxon test, and one-way
      ANOVA were applied to analyze the relationship between Ubc9 expression,
      clinicopathologic features, and clinical response to neoadjuvant chemotherapy.
      The significance of variables for survival was analyzed by the Cox proportional
      hazards model in a multivariate analysis. Kaplan-Meier survival curves were
      plotted and log-rank test was performed. The proportion of Ubc9-positive cells
      was higher in invasive ductal carcinoma than in normal breast tissues [(48.48 +/-
      17.94)% vs. (5.82 +/- 2.80)%, P < 0.001]. High Ubc9 expression was associated
      with poor differentiation (Chi2 = 6.538, P = 0.038), larger tumor size (Chi2 =
      4.701, P = 0.030), advanced clinical stage (Chi2 = 4.651, P = 0.031), lymph node
      metastasis (Chi2 = 9.913, P = 0.010), basal-like phenotype (Chi2 = 8.660, P =
      0.034), and poor clinical response to neoadjuvant chemotherapy (Chi2 = 11.09, P =
      0.001). The expected 6-year cumulative disease-free survival rate was 87.32% in
      patients with low Ubc9 expression compared to 68.78% in those with high Ubc9
      expression (Chi2 = 4.289, P = 0.038). These data indicate that high Ubc9
      expression correlates with poor response to chemotherapy and poor clinical
      prognosis.

PMID- 21880186
TI  - Neoadjuvant chemotherapy for locally advanced cervical cancer reduces surgical
      risks and lymph-vascular space involvement.
AB  - Neoadjuvant chemotherapy (NACT), which can reduce the size and therefore increase
      the resectability of tumors, has recently evolved as a treatment for locally
      advanced cervical cancer. NACT has been reported to decrease the risk of
      pathologic factors related to prognosis of cervical cancer. To further assess the
      effects of NACT on surgery and the pathologic characteristics of cervical cancer,
      we reviewed 110 cases of locally advanced cervical cancer treated with radical
      hysterectomy with or without NACT at the People's Hospital of Peking University
      between January 2006 and December 2010. Of 110 patients, 68 underwent platinum
      based NACT prior to surgery (NACT group) and 42 underwent primary surgery
      treatment (PST group). Our results showed 48 of 68 (70.6%) patients achieved a
      complete response or partial response to NACT. Estimated blood loss, operation
      time, and number of removed lymph nodes during surgery, as well as complication
      rates during and after surgery were not significantly different between the NACT
      group and the PST group. The rates of deep stromal invasion, positive parametria,
      positive surgical vaginal margins, and lymph node metastasis were not
      significantly different between the two groups. However, the rate of lymph
      vascular space involvement (LVSI) was significantly lower in the NACT group than
      in the PST group (P = 0.021). In addition, the response rate of NACT was
      significantly higher in the patients with chemotherapeutic drugs administrated
      via artery than via vein. Our results suggest that NACT is a safe and effective
      treatment for locally advanced cervical cancer and significantly decreases the
      rate of LVSI.

PMID- 21880187
TI  - Rotator cuff lesions with shoulder stiffness: updated pathomechanisms and
      management.
AB  - Few previous studies have investigated the pathomechanism and managements of
      rotator cuff lesions with shoulder stiffness. Based on observations by Codman in
      1934, frozen shoulder presumably relates to rotator cuff tendenitis. In the past
      six decades, tended to discriminate primary frozen shoulder from secondary
      shoulder stiffness due to shoulder disorders such as rotator cuff lesions or
      trauma. Intrinsic degeneration and outlet acromial spur impingement are reported
      as pathogenic causes of rotator cuff lesion. Although patients with rotator cuff
      lesions with shoulder stiffness or adhesive capsulitis (frozen shoulder) may have
      similar complaints about pain and motion limitation, the pathological reactions
      in these disorders remain unclear. In our investigation of clinical vignettes of
      shoulder stiffness, inflammation-mediated adhesions in the subacromial bursa in
      rotator cuff lesions, and changes in inflammatory cytokine levels have been
      linked to myofibroblast recruitment in the subacromial bursa. Our study provides
      the first indication that increased interleukin -1beta expression and
      myofibroblast recruitment in the subacromial bursa are correlated with rotator
      cuff lesions with shoulder stiffness. Increased inflammatory cytokine
      concentrations in the lesions also provide new molecular insight into the
      pathological role of the subacromial bursa in the development of shoulder
      stiffness in rotator cuff lesions. Although rotator cuff repair is a shoulder
      tightening procedure and is not recommended until resolution of the shoulder
      stiffness in rotator cuff lesions with stiff shoulder, our clinical evidence
      based survey suggests that a combined procedure of manipulation, lysis of
      adhesions, acromioplasty, and rotator cuff repair is a useful procedure if the
      symptoms do not improve 3 months of aggressive rehabilitation.

PMID- 21880188
TI  - Facial asymmetry: etiology, evaluation, and management.
AB  - Facial asymmetry is common in humans. Significant facial asymmetry causes both
      functional as well as esthetic problems. When patients complain of facial
      asymmetry, the underlying cause should be investigated. The etiology includes
      congenital disorders, acquired diseases, and traumatic and developmental
      deformities. The causes of many cases of developmental facial asymmetry are
      indistinct. Assessment of facial asymmetry consists of a patient history,
      physical examination, and medical imaging. Medical imaging is helpful for
      objective diagnosis and measurement of the asymmetry, as well as for treatment
      planning. Components of soft tissue, dental and skeletal differences contributing
      to facial asymmetry are evaluated. Frequently dental malocclusion, canting of the
      occlusal level and midline shift are found. Management of facial asymmetry first
      aims at correcting the underlying disorder. Orthognathic surgery is performed for
      the treatment of facial asymmetry combined with dental occlusal problems. A
      symmetrical facial midline, harmonious facial profile and dental occlusion are
      obtained from treatment. Additional surgical procedures may be required to
      increase or reduce the volume of skeletal and soft tissue components on both
      sides to achieve better symmetry.

PMID- 21880189
TI  - Current status of vertebroplasty for osteoporotic compression fracture.
AB  - Vertebral compression fracture is the most common complication of osteoporosis.
      It may result in persistent severe pain and limited mobility, and significantly
      impact the quality of life. Conservative therapy using external bracing, bed rest
      and analgesics is necessary for pain control in these patients. However, some
      patients may experience protracted or ongoing pain even with these measures.
      Surgical treatment is indicated when conservative treatment fails, or in patients
      with spinal instability or neurologic deficit. Elderly patients often have
      comorbilities, and because of osteoporosis, high risk of postoperative
      complications such as implant loosening, and further adjacent fractures.
      Vertebroplasty involves a percutaneous injection of bone cement into the
      collapsed vertebrae under fluroscopic imaging guidance. It was first reported in
      1987 for the management of a painful, aggressive hemangioma of a vertebral body.
      Since then, vertebroplasty has been widely accepted for the treatment of
      vertebral osteoporotic compression fractures without neurological damage. This
      article summarizes the advances in vertebroplasty, and discusses the indications,
      technique, alternative methods, results and complications. The contents include a
      review of the supporting evidence to provide a comparison of the safety and
      efficacy of vertebroplasty and kyphoplasty.

PMID- 21880190
TI  - Survivin expression in cardiac myxoma.
AB  - BACKGROUND: Cardiac myxoma, the most common primary tumor of the heart, has
      variable clinical presentations and an immunohistochemical profile. Survivin, an
      antiapoptosis protein, may play an important role in the causes of cardiac
      myxoma. This investigation will report the expression pattern of survivin in
      cardiac myxomas. METHODS: This study included 40 patients with cardiac myxoma,
      who were treated with surgical excision of the lesion. Detailed clinical
      parameters were reported and the expression of survivin was studied by
      immunohistochemical staining. RESULTS: The patient population was comprised of 24
      (60%) women and 16 (40%) men. The mean age of the patients was 42 years, with an
      age range of 30 to 63 years. All study cases were sporadic myxomas rather than
      familial myxoma. Patients were asymptomatic (20%), or had dyspnea (40%), stroke
      (15%), chest pain (12%), and fever (12%) on presentation. All lesions were
      located in the left atrium. The location of the myxoma and clinical events did
      not differ in terms of pathological changes, such as vascular proliferation,
      inflammation, cellularity, hyaline, calcification and thrombosis. Cardiac myxoma
      was characterized by a survivin dependent pathway with 100% immunohistochemical
      staining in the cytoplasm and the distribution in scoring system of survivin
      expression were 1 case (2.5%) in score 1; 12 cases (30%) in score 2; 12 cases
      (30%) in score 3 and 15 (37.5%) in score 4. CONCLUSION: Cardiac myxomas
      demonstrate strong expression of survivin in the cytoplasm. This implies survivin
      may play an important role in the apoptosis pathway in cardiac myxomas.

PMID- 21880191
TI  - Shockwaves enhance the osteogenetic gene expression in marrow stromal cells from
      hips with osteonecrosis.
AB  - BACKGROUND: This in vitro study investigated the angiogenesis and osteogenesis
      effects of shockwaves on bone marrow stromal cells (BMSCs) from hips with
      osteonecrosis. METHODS: BMSCs were harvested from the bone marrow cavity of the
      proximal femur in six patients with osteonecrosis of the femoral head. The
      specimens were divided into four groups, the control, shockwave, shockwave plus
      nomega-nitro- L-arginine methyl ester (L-NAME) and a nitric oxide (NO) donor
      (NOC18) groups. The control group received no shockwaves and was used as the
      baseline. The shockwave group received 250 shockwave impulses at 14 Kv
      (equivalent to 0.18 mJ/mm2 energy flux density). The shockwave plus LNAME group
      was pre-treated with L-NAME before receiving shockwaves. The NOC18 group received
      NOC18 after cell culture for 48 hours. The evaluations included cell
      proliferation (MTT) assay, alkaline phosphatase, real time reverse transcriptase
      polymerase chain reaction analysis of vessel endothelial growth factor (VEGF),
      bone morphogenic protein (BMP)-2, RUNX2 and osteocalcin mRNA expression and von
      Kossa stain for mineralized nodules. RESULTS: The shockwave group showed
      significant increases in MTT, VEGF, alkaline phosphatase, BMP2, RUNX2 and
      osteocalcin mRNA expression and more mature mineralized nodules compared with the
      control. Pre-treatment with L-NAME significantly reduced the angiogenic and
      osteogenic effects of extracorporeal shockwave therapy (ESWT) and the results
      were comparable with the control. Administration of NOC18 significantly enhanced
      the angiogenesis and osteogenesis effects compared with the control and the
      results were comparable with the shockwave group. CONCLUSION: ESWT significantly
      enhanced the angiogenic and osteogenic effects of BMSCs mediated through the NO
      pathway in hips with osteonecrosis. These innovative findings, at least in part,
      explain some of the mechanism of shockwaves in osteonecrosis of the hip.

PMID- 21880192
TI  - Increased interleukin-6 level in Taiwanese schizophrenic patients.
AB  - BACKGROUND: Schizophrenia is accompanied by an activation of the
      immune/inflammatory system. In the present study, the relationships between serum
      interleukin (IL)-6, tumor necrosis factor (TNF)-alpha, and transforming growth
      factor (TGF)-beta1 levels and schizophrenia were explored in a group of Taiwanese
      inpatients. Furthermore, the serum IL-6, TNF-alpha, and TGF-beta1 levels of
      patients with schizophrenia were compared before and after 1 month of
      antipsychotic treatment. METHODS: The serum IL-6, TNF-alpha, and TGF-beta1 levels
      of 34 acute stage schizophrenic patients and 30 healthy control subjects were
      collected. These levels were again collected in the 34 patients after 1 month of
      antipsychotic treatment. An analysis of covariance (ANCOVA) adjusted for gender
      was performed to examine the differences in cytokine levels between the
      schizophrenic patients and the control group. Repeated measures ANCOVA adjusted
      for gender was performed to examine the differences in cytokine levels of the
      schizophrenic patients before and after 1 month of treatment. RESULTS: Using
      ANCOVA adjusted for gender, significantly increased IL-6 levels were found in
      schizophrenic patients compared with the control group (p = 0.02), but there were
      no significant differences in TNF-alpha and TGF-beta1 levels (p = 0.06 and 0.91,
      respectively). After 1 month of medical treatment, there were no significant
      differences in IL-6 (p = 0.64), TNF-alpha (p = 0.48), and TGF-beta1 (p = 0.23)
      levels in the schizophrenic patients, although IL-6 appeared to be normalizing.
      CONCLUSION: An increase in the IL-6 level may play a role in the pathophysiology
      of schizophrenia. A larger sample size and a longer period of follow-up are
      needed to confirm this finding.

PMID- 21880193
TI  - Efficacy and tolerability of salmeterol/fluticasone propionate versus fluticasone
      propionate in asthma patients: a randomized, double-blind study.
AB  - BACKGROUND: A combination of salmeterol and fluticasone propionate (SAL/FP) has
      been shown to be effective in the treatment of asthma. We compared the efficacy
      and tolerability of SAL/FP (50/250 MUg) with fluticasone propionate (FP) 250 MUg
      administrated twice daily for 2 weeks in treating patients with mild to moderate
      asthma. METHODS: This was a randomized, double-blind study in adult patients with
      symptomatic asthma that was not controlled by 1000 MUg/d inhaled corticosteroids
      (ICS) alone. 48 asthmatics were randomized to receive 2 inhalations of SAL/FP
      50/250 MUg bis in die (BID) or 2 inhalations of FP 250 MUg BID, both delivered
      via Accuhaler device, for 2 weeks. The primary objective was the mean change from
      baseline in the mean morning peak expiratory flow (PEF) over the two week period.
      Other parameters included lung function, daily asthma symptom scores, evening
      PEF, percentage of days free of rescue medication use and daily rescue medication
      use. Tolerability was assessed by adverse events spontaneously elicited at clinic
      visits. RESULTS: 46 patients provided evaluable efficacy for analysis. The
      morning PEF improved significantly throughout the two weeks of treatment compared
      with baseline in the SAL/FP group. Mean morning PEF was 23.0 L/min higher in
      SAL/FP group than in FP group (p = 0.013). The change of forced expiratory volume
      in one second (FEV1) from baseline was greater in SAL/FP group compared to FP
      group (p = 0.048). There were similar effects on day-time and night-time symptom
      scores, percentage symptom free days and nights and usage of salbutamol. 70.8% of
      the patients receiving SAL/FP were satisfied with the treatment, while only 26.1%
      of patients receiving FP alone were (p = 0.020). No death or acute exacerbation
      occurred. CONCLUSION: SAL/FP 50/250 MUg was safe and effective, and had a high
      level of patient satisfaction resulting in significantly greater increases in
      morning PEF and FEV1 compared to the use of FP 250 MUg alone.

PMID- 21880194
TI  - Effects of lactoferrin-containing formula in the prevention of enterovirus and
      rotavirus infection and impact on serum cytokine levels: a randomized trial.
AB  - BACKGROUND: Lactoferrin has been shown to exhibit anti-enterovirus 71 (EV71) and
      antirotavirus properties. This trial was conducted to determine whether a formula
      containing bovine lactoferrin (bLF) exerts a protective effect against EV71 or
      rotavirus infection among children from 2 to 6 years old. METHODS: A prospective,
      randomized, single blind clinical trial of an oral supplement containing bLF
      (daily dose approximately 70 to 85 mg) was carried out with healthy children in a
      day care center from March 2002 to June 2003. The incidence of enterovirus or
      rotavirus infection and the serum level of interferon- gamma (IFN-gamma) and
      interleukin-10 (IL-10) were compared between children receiving and not receiving
      bLF. RESULTS: A total of 172 children, 96 in group A, which received bLF, and 76
      in group B which did not receive bLF, completed the trial. During the study
      period, no EV71 was isolated and seroconversion of EV71 antibodies was noted in
      only one child. Fourteen episodes of presumptive enterovirus infection and 12
      episodes of presumptive viral enteritis were detected. No significant differences
      were observed between groups in the incidence of presumptive enterovirus
      infection or viral enteritis or the number of laboratory confirmed enterovirus or
      rotavirus infections. No significant differences were observed in the serum
      levels of IFN-gamma and IL-10 between groups either prior to or following the
      trial. In both groups, IFN-gamma levels increased, but IL-10 was unchanged
      following the trial. CONCLUSION: An oral supplement of bLF at a dose of 70 mg/day
      did not show any benefits in the prevention of EV71 or rotavirus infection, or
      any impact on IFN-gamma or IL-10 serum levels in healthy children in this trial.

PMID- 21880195
TI  - Woodward procedure improves shoulder function in Sprengel deformity.
AB  - BACKGROUND: Sprengel deformity is a congenital failure of descent of the scapula.
      Limited shoulder abduction and cosmetic appearance are the major concerns.
      Although the Woodward procedure reportedly affords satisfactory correction, the
      long-term functional outcome postoperatively has not been addressed. METHODS:
      Eight patients (9 shoulders) who underwent the Woodward procedure for Sprengel
      deformity were evaluated. The cosmetic appearance and functional results of the
      shoulders were evaluated using the Cavendish grading system and functional
      Constant scoring. Grading of the cosmetic appearance, range of motion of the
      shoulder, and radiographs were obtained for interpretation. RESULTS: After a mean
      follow-up of 113 +/- 29 months, the cosmetic appearance had improved. The
      Cavendish cosmetic grade improved significantly (p = 0.000). The superior
      displacement ratio decreased from 0.5 +/- 0.1 to 0.2 +/- 0.1 (p = 0.004). The
      height-to-width ratio of the affected scapula increased from 1.3 +/- 0.2 (range
      1.1 to 1.7) to 1.6 +/- 0.2 (range 1.4 to 2.0) (p = 0.001). The abduction of the
      shoulder improved from 122 +/- 14 (range 100 to 140) degrees to 157 +/- 20 (range
      125 to 180) degrees (p = 0.008). The average abduction power of the involved
      shoulders was 21.8 +/- 3.2 lbs, which was not significantly different from the
      uninvolved shoulders 23.1 +/- 2.5 lb (p = 0.525). The average Constant score for
      the operated shoulders was 91.7 +/- 4.2 (range 82 to 96) points. CONCLUSION: The
      Woodward procedure offers substantial improvement of shoulder function and
      cosmetic appearance for patients.

PMID- 21880196
TI  - Autonomic activity difference during continuous positive airway pressure
      titration in patients with obstructive sleep apnea/hypopnea syndrome with or
      without hypertension.
AB  - BACKGROUND: Current evidence suggests that obstructive sleep apnea-hypopnea
      syndrome (OSAHS) is an independent risk factor for systemic hypertension. The
      mechanisms linking OSAHS to hypertension remain unclear. However, recent studies
      have indicated that abnormal autonomic control may be an important factor. Our
      study aims to evaulate differences in autonomic activity between hypertensive and
      normotensive OSAHS patients before and during continuous positive airway pressure
      (CPAP) therapy. METHODS: Fifty-three OSAHS patients were analyzed in this study.
      Patients were divided into 2 groups, one group comprising patients with
      hypertension and the other of patients without hypertension. Heart rate
      variability (HRV) was assessed by polysomnography, before patients received CPAP
      titration and during CPAP titration. Then, HRV was compared between the
      hypertensive and normotensive groups. Multivarate analyses were used to evaluate
      the influence of clinical variables on autonomic activity. RESULTS: Although HRV
      before CPAP titration was not statistically different between the 2 groups, low
      frequency variability was significantly lower in hypertensive subjects who
      received CPAP titration compared with normotensive subjects. Multivariate
      analysis revealed that hypertension is a determinant factor of autonomic change
      during CPAP use. CONCLUSIONS: Our findings demonstrate that CPAP therapy results
      in a greater and immediate change in autonomic activity in hypertensive OSAHS
      patients compared with normotensive OSAHS patients. This suggests that CPAP
      lowers blood pressure by decreasing the patient's autonomic activity.

PMID- 21880197
TI  - Higher serum potassium level associated with late stage chronic kidney disease.
AB  - BACKGROUND: The serum potassium (K+) level is kept in a narrow range to sustain
      normal physiology within the human body by the kidneys. The serum K+ level in
      different stages of chronic kidney disease (CKD) remains undefined. METHODS: We
      conducted a cross-sectional study to observe the serum K+ level in patients
      without clinical manifestations of hyperkalemia in the late stages of CKD (stages
      3-5). A total of 531 patients with late stage CKD were included and followed up
      for at least 1 year, from March 2006 to May 2007. The patients were sub-grouped
      by stages of CKD, which were determined by a "Modification of Diet in Renal
      Disease" equation estimating the glomerular filtration rate (eGFR). The serum
      creatinine, eGFR and K+ levels were recorded at least twice during the study. We
      analyzed the average K+ level in these late-stage CKD patients. RESULTS: The
      average K+ level increased along with renal function deterioration in the late
      stages of CKD (stage 3: 4.36 +/- 0.49; stage 4: 4.50 +/- 0.55; stage 5: 4.69 +/-
      0.73 mEq/L, p < 0.05). Men and patients with diabetes mellitus, a low eGFR, and a
      low hemoglobin might have higher levels of serum K+. We also noticed that there
      was a linear increase in the standard deviation of the serum K+ level as renal
      function deteriorated. The use of angiotensin-converting enzyme inhibitors and
      angiotensin II receptor blockers was not associated with hyperkalemia in our
      patients. CONCLUSION: Our results reflected that the serum K+ level increased in
      correlation with the decline in the eGFR in the late stages of CKD. Also, male
      gender, diabetes mellitus, and anemia might be risk factors for higher K+ levels
      in CKD patients. The variation in the serum K+ level became wider as renal
      failure progressed.

PMID- 21880198
TI  - Clinical analysis and strategy for liver transplantation in patients with pre
      existing portal vein thrombosis.
AB  - BACKGROUND: Liver transplantation (LT) in patients with portal vein thrombosis
      (PVT) remains a challenge for transplant surgeons. In this study, we included a
      group of patients with PVT who underwent LT, and analyzed patient outcomes.
      METHODS: A total of 356 patients who underwent LT consisting of 167 cases of
      deceased donor LT and 189 cases of live donor LT at Chang Gung Memorial Hospital
      Linkou Medical Center between September 1996 and June 2009 were retrospectively
      reviewed; 24 (6.7%) of these patients had PVT at transplantation. Their clinical
      features, surgical management, and outcomes were analyzed. RESULTS: Surgical
      management of patients with PVT included a thrombectomy followed by direct
      anastomosis between the recipient's and the liver graft portal vein (PV) (n =
      13), interposition vein graft between the recipient's coronary vein (CV) and the
      liver graft PV (n = 3), direct anastomosis of the recipient's CV and the liver
      graft PV (n = 1), interposition jump graft from the recipient's superior
      mesenteric vein to the liver graft PV (n = 4), and transection of the thrombotic
      PV followed by interposition of a venous graft between the recipient's PV and the
      liver graft PV (n = 3). There were 7 hospital mortalities. The mean follow-up for
      the 17 surviving patients was 36.3 months (range, 3.4-105.1 months), and 14
      patients were still alive at the end of the study. Four patients (16.7%) had
      rethrombosis of portal inflow after LT. Patients with PVT undergoing LT had a
      significantly higher mortality rate (p = 0.033) than patients without PVT
      undergoing LT. However, there was no significant difference in the cumulative
      survival rates (p = 0.0696). Further analysis of patient survival according to
      PVT grade, venous graft application, and reconstructed portal flow routes also
      exhibited no significant differences. CONCLUSIONS: LT for patients with PVT is
      clinically feasible and should not be considered a contraindication. However, a
      favorable outcome is achievable only with ideal surgical management to overcome
      PVT during LT.

PMID- 21880199
TI  - Cervical posterior triangle castleman's disease in a child - case report &
      literature review.
AB  - The most prominent sites of Castleman's disease (CD) are the thorax (mediastinum
      or lung hilum) and abdomen. It rarely occurs in the cervical area and only one
      case has been reported in the posterior triangle of the neck. We report a new
      case of cervical posterior triangle CD in a child. A 9-year-old boy presented
      with an indolent mass in the posterior triangle (level V) on the left side of his
      neck for more than six months. Complete excision was undertaken and the
      histopathological diagnosis was CD of the hyaline-vascular type. At the 3-year
      follow up, there were no signs of recurrence. The etiologies of persistent
      cervical lymphadenopathy in children vary. Though it is very rare, we should keep
      in mind that CD is possible. In addition, CD can be either localized (unicentric)
      or diffuse (multicentric). The treatment and prognosis of these two are quite
      different. Therefore, for any case of CD, systemic evaluation is recommended for
      a precise diagnosis and proper management.

PMID- 21880200
TI  - The treatment of fetishism in an adolescent with attention deficit hyperactivity
      disorder.
AB  - Fetishism is characterized by recurrent, intense sexual fantasy or behavior
      involving the use of nonliving objects, such as women's undergarments, over a
      period of at least six months. This disorder occurs mostly in males and usually
      begins in adolescence. The neurobiological etiologies of fetishism remain
      unclear, and studies on treatment were limited. We present a 14- year-old boy
      with attention deficit hyperactivity disorder with fetishistic behavior who was
      treated successfully with 36 mg extended-release methylphenidate daily and 4
      months of cognitive-rational emotive psychotherapy.

PMID- 21880201
TI  - Serum IL-9 levels and sublingual immunotherapy: preliminary report.
AB  - Th9 is a new T cell subset characterized by IL-9 production. It has been reported
      that serum IL-9 levels are related with symptom severity in patients with
      allergic rhinitis (AR). This study is aimed at investigating whether serum IL-9
      may be modulated by sublingual immunotherapy (SLIT) in patients with persistent
      AR due to Parietaria allergy. Twenty-one AR patients (9 males, median age 41
      years) successfully treated with SLIT and 52 AR patients (25 males, median age 34
      years) treated only with drugs were evaluated during the pollen season. Serum IL
      9 was dosed in all patients. SLIT-treated patients showed significantly lower
      serum IL-9 levels than untreated AR patients (p <0.0001). In conclusion, this
      preliminary study shows that a single pre-seasonal SLIT course might modulate
      serum IL-9.

PMID- 21880202
TI  - Present status and new perspectives in laser welding of vascular tissues.
AB  - The laser welding of biological tissues is a particular use of lasers in surgery.
      The technique has been proposed since the 1970s for surgical applications, such
      as repairing blood vessels, nerves, tendons, bronchial fistulae, skin and ocular
      tissues. In vascular surgery, two procedures have been tested and optimized in
      animal models, both ex vivo and in vivo, in order to design different approaches
      for blood vessels anastomoses and for the repair of vascular lesions: the laser
      assisted vascular anastomosis (LAVA) and the laser-assisted vessel repair (LAVR).
      Sealing tissues by laser may overcome the problems related to the use of
      conventional closuring methods that are generally associated with various degrees
      of vascular wall damage that can ultimately predispose to vessel thrombosis and
      occlusion. In fact, the use of a laser welding technique provides several
      advantages such as simplification of the surgical procedure, reduction of the
      operative time, suppression of bleeding, and may guarantee an optimal healing
      process of vascular structures, very similar to restitutio ad integrum. Despite
      the numerous preclinical studies performed by several research groups, the
      clinical applications of laser-assisted anastomosis or vessel repair are still
      far off. Substantial breakthrough in the laser welding of biological tissues may
      come from the advent of nanotechnologies. Herein we describe the present status
      and the future perspectives in laser welding of vascular structures.

PMID- 21880203
TI  - Skewed T-cell receptor repertoire: more than a marker of malignancy, a tool to
      dissect the immunopathology of inflammatory diseases.
AB  - The highly diverse heterodimeric surface T cell receptor (TCR) gives the T
      lymphocyte its specificity for MHC-bound peptides needed to initiate antigen
      recognition. In normal peripheral blood, spleen and lymph nodes, the TCR
      repertoire of the T lymphocytes is usually polyclonal. However, in malignancies
      such as leukemias, as well as in lymphoproliferative diseases of mature T cells,
      the TCR is a reflection of the clonality of the malignant cells and is therefore
      monoclonal. Several clinical conditions (mainly solid tumors and autoimmune
      diseases) have been described where the TCR repertoire is restricted. The ability
      to demonstrate clonal TCR usage provides a useful tool to dissect the
      immunopathology of inflammatory diseases. In this review we discuss these
      findings and propose to sub-divide diseases with restricted TCR repertoire into a
      group of conditions in which there is a known TCR ligand, as opposed to diseases
      in which the restricted TCR repertoire is the result of impaired T-cell
      development. This classification sheds light on the pathogenesis of several
      inflammatory diseases.

PMID- 21880204
TI  - Psychological stress and vitamins.
AB  - Conditions of stress and anxiety have complex interactions with insufficient
      vitamin intake and malnutrition. This study, based on literature research in
      Medline, analyzes the inter-relationship between vitamins and stress. This report
      concerns a number of vitamins that have been receiving much attention in earlier
      reviews of the literature, for their potential to protect against stress-related
      events, and focus is placed upon recent findings.

PMID- 21880205
TI  - GABA representation in hypoxia sensing: a ventilatory study in the rat.
AB  - Phenibut, a nonspecific GABA derivative, is clinically used as an anxiolytic and
      tranquilizer in psychosomatic conditions. A GABA-ergic inhibitory pathway is
      engaged in respiratory control at both central and peripheral levels. However,
      the potential of phenibut to affect the O2-related chemoreflexes has not yet been
      studied. In this study we seek to determine the ventilatory responses to changes
      in inspired O2 content in anesthetized, spontaneously-breathing rats. Steady
      state 5-min responses to 10% O2 in N2 and 100% O2 were taken in each animal
      before and 1 h after phenibut administration in a dose 450 mg/kg, i.p. Minute
      ventilation and its frequency and tidal components were obtained from the
      respiratory flow signal. We found that after a period of irregular extension of
      the respiratory cycle, phenibut stabilized resting ventilation at a lower level
      [20.0+/-3.3 (SD) vs 31.1+/-5.2 ml/min before phenibut; P<0.01]. The ventilatory
      depressant effect of phenibut was not reflected in the hypoxic response. In
      relative terms, this response was actually accentuated after phenibut; the peak
      hypoxic ventilation increased by 164% from baseline vs the 100% increase before
      phenibut. Regarding hyperoxia, its inhibitory effect on breathing was more
      expressed after phenibut. In conclusion, the GABA-mimetic phenibut did not
      curtail hypoxic ventilatory responsiveness, despite the presence of GABA-ergic
      pathways in both central and peripheral, carotid body mechanisms mediating the
      hypoxic chemoreflex. Thus, GABA-mediated synaptic inhibition may be elaborated in
      a way to sustain the primarily defensive ventilatory chemoreflex.

PMID- 21880206
TI  - Changes of immunomodulatory cytokines associated with omalizumab therapy for
      severe persistent asthma.
AB  - Omalizumab is an anti-IgE monoclonal antibody that was proven effective for the
      treatment of severe asthma. IgE plays a central role in allergic asthma, and an
      anti-allergic effect of omalizumab has been confirmed in terms of its impact on
      Th2 cytokines. The objective of the present study is to determine the influence
      of omalizumab on clinical parameters and circulating immuoregulatory cytokines.
      Patients with severe allergic asthma were enrolled and given four months of
      omalizumab therapy. Changes of symptoms and other parameters were assessed,
      including the asthma control test (ACT) score, morning peak expiratory flow
      (PEF), peripheral eosinophil count, total serum IgE, and pulmonary function
      tests. The use of corticosteroids and short-acting bronchodilators, as well as
      the number of unscheduled hospital visits, were monitored. Circulating levels of
      cytokines were analyzed with a multiplex cytokine immunoassay in patients with or
      without omalizumab therapy. Asthma symptoms (evaluated by the ACT score and
      morning PEF) improved with omalizumab treatment, while total IgE was elevated.
      Use of corticosteroids and short-acting bronchodilators and the number of
      unscheduled hospital visits for exacerbation of asthma were all reduced by
      omalizumab treatment. The level of macrophage inflammatory protein 1-delta (MIP1
      delta) was significantly reduced after omalizumab therapy and was high in
      patients without omalizumab. IL-16 also tended to decrease with omalizumab
      therapy. Both MIP1-delta and IL-16 decreased as asthma improved over the 4-month
      period of omalizumab therapy. These findings suggest that omalizumab may act via
      IgE-mediated immunoregulation of MIP1-delta and IL-16.

PMID- 21880207
TI  - Beneficial nutraceutical modulation of cerebral erythropoietin expression and
      oxidative stress: an experimental study.
AB  - The main object of this study is to examine the effect of Klamin(r), a
      nutraceutical containing phenylethylamine, phycocyanins, mycosporine-like
      aminoacids and aphanizomenon flos aquae-phytochrome on the learning and memory
      ability, the oxidative status and cerebral erythropoietin and its receptor
      EPO/EPOR system in prematurely senescent (PS) mice. A total of 28 PS mice,
      selected according to a prior T-maze test, and 26 non-prematurely senescent mice
      (NPS) mice were chosen. PS animals were divided into 3 groups and followed for 4
      weeks: A) normal chow diet; B) added with Klamin(r) at 20 mg/kg/day (low dose);
      C) added with Klamin(r) at 100mg/kg/day (high dose). A further group of NPS mice
      given either normal food (group D) or high dose Klamin(r) (group E) was also
      considered. The behavioral procedures of spatial learning ability (Morris test)
      showed that PS mice had significantly longer learning time as compared to their
      NPS counterpart (p<0.01), but this effect was prevented especially in mice
      supplemented with high-dose Klamin(r) (p<0.05) which improved performances in NPS
      mice (p<0.05). High-dose Klamin(r) supplementation restored the depleted total
      thiol concentration in the brain observed in PS mice while normalizing their
      increased malonildialdehyde level (p<0.05). Moreover, the high-dosage only caused
      a significant upregulation of EPO/EPOR system both in PS and in NPS animals
      (p<0.05). Taken together, these data suggest that this specific alga Klamath
      extract has considerable antioxidant and adaptogenic properties, also through a
      stimulatory effect of cerebral EPO/EPO system.

PMID- 21880208
TI  - Immune responses to porphyromonas gingivalis infection suppress systemic
      inflammatory response in experimental murine model.
AB  - Periodontitis is a localized infectious disease caused by periodontopathic
      bacteria such as Porphyromonas gingivalis (P. gingivalis), and the severity
      correlates to significance of immune responses. Recently, it has been reported
      that periodontitis is associated with the development of systemic disease such as
      diabetes and atherosclerosis because of increasing invasion of oral pathogens to
      the circulation. However, the association between local and systemic infectious
      responses is still unclear. In the present study, we examined the differences of
      biological responses in animals with or without bacterial infection. After Balb/c
      mice were infected subcutaneously with live P. gingivalis W83, serum, skin and
      liver were collected according to experimental protocol. The skin and liver
      tissues were observed pathologically by haematoxylin-eosin staining, and serum IL
      6 levels were measured using ELISA method. Throughout the experimental period,
      conditions of the mice were observed continuously. As expected, severe
      infiltration of leukocytes were observed at inflamed skin corresponding to the
      number of bacterial challenges. Although no inflammatory appearance of skin was
      observed, serum IL-6 levels were increased dramatically (P <0.01, Student's t
      test) and liver tissues were injured in the mice without bacterial challenge.
      Interestingly, although severe inflammatory appearance of the skin was observed,
      serum IL-6 levels were not increased and no inflammatory responses were observed
      in the liver of the 3-times bacterially challenged group. Importantly,
      immunoglobulin G against P. gingivalis W83 was detected in the blood of mice with
      3-times bacterial challenge corresponding to improvement of weight loss and
      survival. In conclusion, although multiple infections develop severe localized
      inflammation, the immune system should be sufficient to protect the systemic
      inflammatory responses.

PMID- 21880209
TI  - The effect of the plasticizer diethylhexyl phthalate on transport activity and
      expression of P-glycoprotein in parental and doxo-resistant human sarcoma cell
      lines.
AB  - Multidrug resistance (MDR) to cancer therapy is frequently associated with the
      over-expression of the multidrug transporter MDR1 gene product P-glycoprotein
      (Pgp) in several types of human tumours. Various chemosensitizers have been used
      to inhibit Pgp activity but toxicity limits their clinical application. Di(2
      ethylhexyl)phthalate (DEHP) is a plasticizer that is released from polyvinyl
      chloride (PVC) medical devices. Therefore, cancer patients undertaking
      chemotherapy are exposed to a clinically important amount of DEHP through blood
      and blood component transfusions, apheresis products, intravenous chemotherapy,
      parenteral nutrition and other medical treatments. The present study was designed
      to investigate the effects of DEHP on transport activity and expression of Pgp in
      order to evaluate its potential use as a chemosensitizer in cancer therapy. Human
      doxorubicin (doxo) resistant sarcoma cells (MES-SA/Dx5) that over-express Pgp
      were treated with different doses of doxo (2, 4 and 8 MUM) in the presence or
      absence of various concentrations of DEHP (3, 6 and 12 MUM) that were clinically
      achievable in vivo. Our results show that co-treatment with 2, 4 and 8 MUM doxo
      in the presence of the lowest concentration of DEHP (3 MUM) enhanced
      significantly doxo accumulation in MES-SA/Dx5 cells and, consistently increased
      the sensitivity to doxo, when compared to controls receiving only doxo. In
      contrast, higher DEHP concentrations (6 and 12 MUM) induced MES-SA/Dx5 to extrude
      doxo decreasing doxo cytotoxicity toward resistant cells below control values.
      These results are consistent with the increase in Pgp expression levels in
      parental MES-SA cells treated with 3, 6 and 12 MUM DEHP for 24 h and compared to
      untreated controls. All in all, these findings suggest a potential clinical
      application of DEHP as a chemosensitizer to improve effectiveness of the
      antineoplastic drugs in MDR human tumours.

PMID- 21880210
TI  - High prevalence of latent tuberculosis infection in autoimmune disorders such as
      psoriasis and in chronic respiratory diseases, including lung cancer.
AB  - The early diagnosis and treatment of individuals harboring M. tuberculosis is key
      to ensuring the effectiveness of health programs aimed at the elimination of
      tuberculosis (TB). Monitoring for TB also has other important health care
      implications for the related immune pathology caused by the chronic inflammatory
      response to M. tuberculosis. Moreover, the recent introduction of biologic
      therapies for the treatment of several immune-mediated inflammatory diseases has
      shown unexpected high frequencies of reactivation of latent TB. The present cross
      sectional study is aimed at estimating the prevalence of latent tuberculosis
      infection (LTBI) in different groups of subjects, either undergoing a routine
      program of screening for TB or a clinical monitoring of autoimmune or lung
      disorders, by analyzing their immune response in vitro to a pool of different M.
      tuberculosis antigens through an IFN-gamma-release assay (IGRA). We consecutively
      tested 1,644 subjects including health care workers (931), healthy immigrants
      from different countries (93), patients with a diagnosis of psoriasis (405),
      patients with lung inflammatory disease (60) or lung neoplasia (32) and a group
      of HIV-1 infected Italian subjects (120). The prevalence of IGRAs positive
      responses among health care workers was 8.9 percent. In comparison, significantly
      higher frequencies were found in healthy immigrant subjects (33.3%), similar to
      those found in inflammatory broncho-pneumopathies (34.5%) or lung cancer (29.6%).
      Interestingly, an unexpected high prevalence was also found in patients affected
      by psoriasis (18.0%), while HIV-infected subjects had values comparable to those
      of health care workers (10.8%). An age cut-off was determined and applied for
      each group by receiver operating characteristic (ROC) curves in order to perform
      the statistical analysis among age-comparable groups. Multivariate analysis
      showed that the age and clinical conditions such as having a diagnosis of
      psoriasis or a lung inflammatory disease were independent risk factors for
      developing an IGRA positive response. This study highlights an unprecedented high
      prevalence of IGRA positive responses among patients affected by psoriasis and
      emphasizes the need for a preliminary assessment of LTBI before the
      administration of any biologic therapy based on cytokine antagonists such as anti
      TNF-alpha. Moreover, screening for LTBI should be routinely performed in the
      presence of a chronic pulmonary disease.

PMID- 21880211
TI  - Redox balance signalling in occupational stress: modification by nutraceutical
      intervention.
AB  - There is increasing evidence that psychosocial stress can be viewed as a system
      wide derangement of cellular homeostasis, with heightened oxidative stress and
      triggered proinflammatory mechanisms. The aim of this study is twofold: a) to
      replicate findings that psychological stress increases oxidative damage and b) to
      determine whether a fermented papaya preparation known to exert significant
      protective antioxidant properties could buffer such increases in nuclear DNA
      damage while also inducing epigenetic protective mechanisms. Twenty-eight
      sedentary men and women (age range: 28-52), who reported living a stressful
      lifestyle but with an overall positive attitude, were recruited for this study.
      Chronic diseases as well as severe burnout and use of drugs for anxiety
      constituted exclusion criteria. Subjects were supplemented for 1 month with 9
      g/day (4.5 g twice a day) of a certified fermented papaya preparation. All
      subjects were given a stress and sleep quality questionnaire together with a diet
      and life style assessment. Blood was collected at 2 and 4 week, erythrocyte and
      leukocyte were separated to assess redox balance and heme oxygenase-1 (HO-1) gene
      expression while bilirubin oxidized metabolites (BOMs) were tested in the urine.
      Stressed individuals showed a significant abnormality of redox status with
      increased MDA of erythrocyte and increased level of 8-0HdG in leukocyte and BOMs
      excretion (p<0.05). Nutraceutical supplementation brought about a normalization
      of such values already at the 2 week observation (p<0.05) together with a
      significant upregulation of HO-1 (p<0.01). Taken together, the results of this
      study confirm that stressful occupational life per se, without any overt
      psychiatric illness, may be associated to increased oxidative stress.
      Supplementation with functional food affecting redox regulation may be part of
      the therapeutic armamentarium to be considered in this clinical setting.

PMID- 21880212
TI  - A method to evaluate dynamics and periodicity of hormone secretion.
AB  - Spontaneous hormone secretory dynamics include tonic and pulsatile components and
      a number of periodic processes. Circadian variations are usually found for
      melatonin, TSH and GH, with peak secretions at night, and in cortisol secretion,
      which peaks in the morning. Free thyroxine (FT4) and insulin-like growth factor
      (IGF)1 levels do not always change with circadian rhythmicity or show only minor
      fluctuations. Fractional variations explore the dynamics of secretion related to
      time intervals, and the rate of change in serum levels represents a signal for
      the receptorial system and the target organ. We evaluated time-related variations
      and change dynamics for melatonin, cortisol, TSH, FT4, GH and IGF1 levels in
      blood samples obtained every 4 h for 24 h from eleven healthy males, ages 35-53
      years (mean ? SE 43.6 +/- 1.7). Nyctohemeral (i.e., day-night) patterns of
      hormone secretion levels and the fractional rate of variation between consecutive
      4-hourly time-qualified hormone serum levels (calculated as percent change from
      time 1 to time 2) were evaluated for circadian periodicity using a 24 and 12-h
      cosine model. A circadian rhythm was validated for serum level changes in
      cortisol with peaks of the 24-h cosine model at 07:48 h, and melatonin, TSH and
      GH, with phases at 01:35 h, 23:32 h, and 00:00 h, respectively. A weak, but
      significant, 12-h periodicity was found for FT4 serum levels, with minor peaks in
      the morning (10:00 h) and evening (22:00 h), and for IGF1, with minor peaks in
      the morning (07:40 h) and evening (19:40 h). Circadian rhythmicity was found in
      the 4-hourly fractional variations with phases of increase or surge at 02:00 h
      for cortisol, 22:29 h for melatonin, 05:14 h for FT4, and 21:19 h for GH. A
      significant 12-h periodicity was found for the 4-hourly fractional variations of
      TSH with two peaks in the morning (decrease or drop at 04:42 h) and afternoon
      (surge at 16:28 h), whereas IGF1 fractional variation changes did not show a
      significant rhythmic pattern. In conclusion, the calculation of the time
      qualified fractional rate of variation allows evaluation of the dynamics of
      secretion and the specification of the timepoint(s) of maximal change of
      secretion, not only for hormones whose secretion is characterized by a circadian
      pattern of variation, but also for hormones that show no circadian or only weak
      ultradian (12 h) variations (i.e., FT4).

PMID- 21880213
TI  - Molecular characterization of novel melanoma cell lines.
AB  - We isolated two novel cell lines from different types of sporadic human malignant
      melanoma: the hmel1 line was obtained from a melanoma skin metastasis and the
      hmel9 cell line from a primary superficial spreading melanoma. The karyotype and
      pigmentation parameters were assessed in these cell lines. Cytogenetic analysis
      in early stages of culture revealed that both cell lines had chromosome
      instability and simultaneous growth of heteroploid subpopulations. The molecular
      analysis of some genes involved in melanoma showed that both cell lines harbor
      BRAF mutations. The unpigmented hmel1 and the pigmented hmel9 lines were found to
      express the tyrosinase gene. The tyrosine hydroxylase activity was detectable
      only in hmel9 cells and practically absent in the hmel1 cell line. This activity
      was found to be correlated with the relative tyrosinase protein amount in both
      melanoma cell lines. The biological behaviour in the two melanoma cell lines,
      derived from two different types of melanoma lesions displaying distinct clinical
      and histopathological features, confirms the heterogeneous characteristics of
      sporadic melanoma. Similarities and/or differences between cell lines extracted
      from different melanoma cases could be useful in the future for diagnostic,
      prognostic and therapeutic purposes.

PMID- 21880214
TI  - Neuro-endocrine correlations of hypothalamic-pituitary-thyroid axis in healthy
      humans.
AB  - Neuro-endocrine hormone secretion is characterized by circadian rhythmicity.
      Melatonin, GRH and GH are secreted during the night, CRH and ACTH secretion peak
      in the morning, determining the circadian rhythm of cortisol secretion, TRH and
      TSH show circadian variations with higher levels at night. Thyroxine levels do
      not change with clear circadian rhythmicity. In this paper we have considered a
      possible influence of cortisol and melatonin on hypothalamic-pituitary-thyroid
      axis function in humans. Melatonin, cortisol, TRH, TSH and FT4 serum levels were
      determined in blood samples obtained every four hours for 24 hours from ten
      healthy males, aged 36-51 years. We correlated hormone serum levels at each
      sampling time and evaluated the presence of circadian rhythmicity of hormone
      secretion. In the activity phase (06:00 h-10:00 h-14:00 h) cortisol correlated
      negatively with FT4, TSH correlated positively with TRH, TRH correlated
      positively with FT4 and melatonin correlated positively with TSH. In the resting
      phase (18:00 h-22:00 h-02:00 h) TRH correlated positively with FT4, melatonin
      correlated negatively with FT4, TSH correlated negatively with FT4, cortisol
      correlated positively with FT4 and TSH correlated positively with TRH. A clear
      circadian rhythm was validated for the time-qualified changes of melatonin and
      TSH secretion (with acrophase during the night), for cortisol serum levels (with
      acrophase in the morning), but not for TRH and FT4 serum level changes. In
      conclusion, the hypothalamic-pituitary-thyroid axis function may be modulated by
      cortisol and melatonin serum levels and by their circadian rhythmicity of
      variation.

PMID- 21880215
TI  - Endothelial activation and injury by cigarette smoke exposure.
AB  - Endothelial activation/injury following exposure to cigarette smoke may explain
      incidence of atherosclerosis and cardiovascular disease in smokers. We
      investigated cigarette smoke extract (CSE) effects relative to activation,
      injury, and survival of human umbilical vein endothelial cells (HUVEC) and
      compared circulating levels of specific endothelial activation markers between
      smokers and healthy non-smokers before and after smoking cessation. Viability and
      toxicity of HUVEC were tested by MTT and LDH assay. Release (by endothelial
      cells) and circulating levels (in smokers) of von Willebrand Factor (vWF),
      thrombomodulin (TM), was evaluated by ELISA. Incubation with increasing
      concentrations of CSE reduced the percentage of viable cells, being 33.9%, 23.9%
      after CSE 4%, 6% respectively. Dose- and time-dependent release of LDH was
      observed after incubation with CSE. vWF, TM release were assayed after CSE 2%
      HUVEC stimulation. Significant 42%, 61%, 76% increase in vWF concentration was
      detected respectively at 30', 60', 120'. Reduction in circulating levels of vWF,
      from a median value of 144.0% to 123.7%, was observed in the quitters group after
      smoking cessation. Exposure to cigarette smoke is cytotoxic and induces
      activation/injury of endothelium in vitro and in vivo. These findings may provide
      pathogenetic basis by which smoking can predispose to development of
      atherothrombosis and cardiovascular disease.

PMID- 21880216
TI  - A systems biology approach: new insights into fetal growth restriction using
      Bayesian Networks.
AB  - IL-6, IGF-II and IGFBP-2 concentrations in placental lysates were previously
      shown to be associated with foetal growth. This study aimed to apply a Bayesian
      Network (BN) model in order to investigate complex dependencies among biochemical
      and clinical factors and fetal growth outcome. Twenty-one Intra-Uterine Growth
      Restricted (IUGR) and 25 Appropriate for Gestational Age (AGA) pregnancies were
      followed throughout pregnancy. Information was collected on maternal and
      gestational age, neonatal gender, previous gynaecological history. Total protein
      content, IGF-II, IGFBP-1, IGFBP-2, IL-6, and TNF-alpha concentrations in
      placental lysates were measured, and IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IL-6
      relative gene expression in placenta assessed. A BN and a hybrid forecasting
      system were implemented: BN revealed a key role of maternal age and TNF-alpha on
      IUGR and confirmed a close relationship among IGF-II, IL-6 and foetal growth. A
      relationship between duration of gestation, appropriateness for gestational age,
      and placental IL-6 concentration was also confirmed. Compared with other
      techniques, BN showed a better accuracy. Findings confirmed a major role of
      maternal age in addition to IGF-II, IL-6 and TNF-alpha in IUGR. A direct role of
      IGFBP-2 was not shown. BN confirmed to be useful in understanding the system's
      biology and graphically representing variable relationships and hierarchy,
      particularly where, as in IUGR, many interactions among predictors exist.

PMID- 21880217
TI  - Statistical analysis of differential gene expression in colorectal cancer using
      CLEAR-test.
AB  - CLEAR test provides a novel method of analysis by combining inference for
      differential expression and variability. Frozen tumor specimens from 14 (3 coded
      Stage I, 5 Stage II, 2 Stage III and 4 Stage IV) colon cancer patients were
      obtained. Archived primary tumor samples were collected at the time of surgery
      and normal colon mucosae (controls specimens) were also collected. The studied
      transcriptomes were clustered using hierarchical agglomeration with Ward's method
      and Tchebychev distance. The separable groups of transcriptomes were classified
      as high clinical stage of adenocarcinoma (HCS; stages II-IV), low clinical stage
      of adenocarcinoma (LCS; stages I and 3 controls), and two normal colon mucosae
      (controls N1 and N2). The results of the CLEAR-test algorithm in normal colon
      specimens and adenocarcinoma specimens with low and high clinical stage showed 50
      most and 50 least significant genes. The list of differential genes (p<0.01) in
      normal colon specimens and adenocarcinoma specimens with low and high clinical
      stage presented 58 genes.

PMID- 21880218
TI  - Anti-tumor necrosis factor treatment in occult hepatitis B virus infection: a
      retrospective analysis of 62 patients with psoriatic disease.
AB  - One of the problems possibly related to the use of biological agents targeting
      tumor necrosis factor (TNF)-alpha is the increased risk of infections, including
      the activation of hepatitis B virus (HBV). HBV activation can occur in carriers
      of hepatitis B surface antigen (HBsAg), but the risk may also involve the HBsAg
      negative (anti-HBc +/- anti-HBs) occult carriers. Precise data on the safety of
      anti-TNF and/or other immunosuppressive drugs in HBV occult carriers are not
      available. We performed a retrospective analysis of 62 psoriatic patients with
      occult HBV infection treated with anti-TNF biological agents over a period of
      approximately 4 years: 44 subjects were treated with etanercept, 8 with
      infliximab and 10 with adalimumab. During the observational treatment period, no
      signs of HBV activation were observed. Only in one patient the reappearance of
      HBsAg, without detectable HBV-DNA, was noted before retreatment with etanercept
      and after 10 months from discontinuation of the previous course. In this patient
      etanercept was re-administered in association with lamivudine without any adverse
      event. Our results suggest the overall safety of treatment with anti-TNF drugs in
      HBV occult carriers, although a careful and constant monitoring of virological
      markers is required in such patients during treatment with anti-TNF drugs in
      order to have an early recognition of viral reactivation.

PMID- 21880219
TI  - A pilot study on the transcriptional response of androgen- and insulin-related
      genes in peripheral blood mononuclear cells induced by testosterone
      administration in hypogonadal men.
AB  - The aim of the present study is to determine whether testosterone (T)
      administration changes the expression profile of androgen- and insulin-related
      genes in peripheral blood mononuclear cells (PBMC). To this end, we evaluated the
      gene expression profile of 19 genes (AKT2, CCND1, GSK3ALPHA, IGF1, GSK3BETA,
      FOXO3, IL6, IGFBP2, UGT2B17, ARA55, CREBBP, CYP11A, HSD17B1, HSD17B7, UGT2B7,
      SELADIN 1, CLU, PGC1, AKR1C1) selected according their function in the androgen
      pathways, in a series of 11 hypogonadal men pharmacologically treated with T. We
      noted that 7 genes were differentially expressed, five of them were up-regulated
      (AKT2 FC=2.39, CREBBP FC=11.2, GSK3beta FC=5.6, UGT2B7 FC=4.49, UGT2B17 FC=2.88)
      and two were down-regulated (ARA55 FC= -2.0, CYP11A FC= -2.47). This experience
      suggests that androgen- and insulin-related genes can be considered useful blood
      genomic biomarkers for specific steroid drugs.

PMID- 21880220
TI  - May nasal hyperreactivity be a sequela of recurrent common cold?
AB  - Respiratory viral infections may worsen bronchial hyperreactivity. However, there
      is no data on the possible role of recurrent infectious rhinitis in nose
      hyperreactivity. This study was therefore designed to investigate whether
      subjects suffering from recurrent common cold have nasal hyperreactivity,
      assessed by histamine nasal challenge. This study included a group of 40 patients
      (19 males, mean age 34.1 years) with history of at least five episodes of common
      cold in the previous year, but without documented allergy, and twenty healthy
      subjects (8 males, mean age 32.3 years) were enrolled as control group, all of
      whom were non-allergic. Nasal provocation test with histamine was performed in
      all subjects. Nasal provocation test with histamine induced a 200% increase in
      nasal resistance after provocation in 24 (60%) patients suffering from recurrent
      viral rhinitis. No normal subject had an increase >180% in nasal resistance.
      There was a significant difference between the patient group and the control
      group (p<0.05). In conclusion, this study shows that nasal hyperreactivity might
      be a sequela of recurrent common cold. Further studies should be conducted to
      confirm this preliminary finding.

PMID- 21880221
TI  - Using insulin in type 2 diabetes: in need of a renaissance?

PMID- 21880223
TI  - Analysis of the environmental impact of insulin infusion sets based on loss of
      resources with waste.
AB  - Insulin pump therapy [continuous subcutaneous insulin infusion (CSII)] requires
      regular change of infusion sets every 2-3 days in order to minimize the risk of
      skin irritations or other adverse events. This has been discussed to be a
      potential burden to the environment. The purpose of this analysis was to perform
      an environmental assessment of insulin pump infusion sets based on loss of
      resources occurring during incineration of the discarded products and by means of
      a lifecycle concept used to weight a material in relation to its rareness on
      earth and its consumption. In addition to five infusion sets (Inset30, InsetII,
      Comfort, Quick-set, and Cleo), a patch pump (Omnipod) was also included in this
      analysis. The annual loss in waste of the so called "person reserve" of 3 days of
      catheter use was compared with daily consumption of a cup of coffee in a
      disposable paper cup and to a soft drink in an aluminum can. The weight-based
      loss in resources through waste for the infusion sets (except for Cleo)
      corresponded to 70-200% of the loss of resources for a coffee cup (Cleo, 320%;
      Omnipod, 1,821,600%) and to 1-3% of the loss from an aluminum soft drink can
      (Cleo, 5%; Omnipod, 31,200%). The loss or resources by use of infusion sets used
      in insulin pump therapy appears to be low and is similar to the burden induced by
      the uptake of one cup of coffee per day. The loss or resources with regular CSII
      is considerably lower than the loss or resources induced by patch pumps.

PMID- 21880222
TI  - Geoenvironmental diabetology.
AB  - Many reports have documented the negative health consequences that environmental
      stressors can have on patients with diabetes. Studies examining the interaction
      between the environment and a patient with diabetes can be unified under a single
      discipline termed "geoenvironmental diabetology." Geoenvironmental diabetology is
      defined more specifically as the study of how geophysical phenomena impact a
      patient with diabetes, to include effects on metabolic control, ancillary
      equipment (e.g., glucometers and insulin pumps), medications, supplies, access to
      care, and influences on the adaptive strategies employed by patients to care for
      their diabetes under extreme circumstances. Geological events such as natural
      disasters (e.g., earthquakes) or extreme weather (e.g., heat waves) are examples
      of stressors that can affect patients with diabetes and that can be included
      under the heading of geoenvironmental diabetology. As proposed here,
      geoenvironmental diabetology refers to how events in the physical world affect
      those with diagnosed diabetes, rather than how environmental factors might
      trigger development of disease. As the global prevalence of diabetes continues to
      increase, including in parts of the world that are especially vulnerable to
      disasters and climate change, further discussion is warranted on how to best
      prepare for management of diabetes under conditions of extreme geological and
      weather events and a changing climate. An overview is presented of various
      studies that have detailed how geoenvironmental phenomena can adversely affect
      patients with diabetes and concludes with a discussion of requirements for
      developing strategies for geoenvironmental diabetes management.

PMID- 21880224
TI  - Analysis: the impact of needle, syringe, and lancet disposal on the community.
AB  - There are over 7.5 billion needles and syringes used outside of the health care
      system each year by individuals with diabetes, migraines, allergies, infertility,
      arthritis, HIV, hepatitis, multiple sclerosis, osteoporosis, psoriasis, or other
      conditions. Disposal of needles, syringes, lancets, and other medical products
      are not regulated in the home, while these same products used in health care
      facilities are strictly regulated. Home-generated medical waste is routinely
      placed into curbside trash, placing sanitation workers and custodial personnel at
      personal risk of a needle-stick injury. The Coalition for Safe Community Needle
      Disposal is working to establish a solution that is satisfactory to all
      stakeholders, sharing the burden of these programs with the pharmaceutical
      industry, medical device industry, waste management industry, recycling
      companies, and local and state governments.

PMID- 21880225
TI  - Waste disposal in the 21st century and diabetes technology: a little coffee (cup)
      or beer (can) with that insulin infusion (set).
AB  - The advent of single-use disposable syringes along with myriad similar products
      for the health care industry has raised interest in the impact of these devices
      on the environment. Interest does not stop at impact of the device, but also
      includes associated pharmaceutical agents. Across the spectrum of health care,
      providers as well as end users of products are assessing the impact of product
      design and contents upon land, air, and water. In this issue of Journal of
      Diabetes Science and Technology, Pfutzner and colleagues tackle the issue by
      focusing on a product for the diabetes patient. As environmental sustainability
      has become part of the evaluation process of many products, their assessment
      sheds some interesting light on the impact of a group of devices when compared
      and contrasted against the ever-popular disposable coffee cup or beer/soda
      aluminum can. Regional variations in waste disposal practices need to be
      understood when conducting these types of assessments.

PMID- 21880226
TI  - Evaluation of a novel continuous glucose measurement device in patients with
      diabetes mellitus across the glycemic range.
AB  - BACKGROUND: This glucose clamp study assessed the performance of an
      electrochemical continuous glucose monitoring (CGM) system for monitoring levels
      of interstitial glucose. This novel system does not require use of a trocar or
      needle for sensor insertion. METHOD: Continuous glucose monitoring sensors were
      inserted subcutaneously into the abdominal tissue of 14 adults with type 1 or
      type 2 diabetes. Subjects underwent an automated glucose clamp procedure with
      four consecutive post-steady-state glucose plateau periods (40 min each): (a)
      hypoglycemic (50 mg/dl), (b) hyperglycemic (250 mg/dl), (c) second hypoglycemic
      (50 mg/dl), and (d) euglycemic (90 mg/dl). Plasma glucose results obtained with
      YSI glucose analyzers were used for sensor calibration. Accuracy was assessed
      retrospectively for plateau periods and transition states, when glucose levels
      were changing rapidly (approximately 2 mg/dl/min). RESULTS: Mean absolute percent
      difference (APD) was lowest during hypoglycemic plateaus (11.68%, 14.15%) and the
      euglycemic-to-hypoglycemic transition (14.21%). Mean APD during the hyperglycemic
      plateau was 17.11%; mean APDs were 18.12% and 19.25% during the hypoglycemic-to
      hyperglycemic and hyperglycemic-to-hypoglycemic transitions, respectively. Parkes
      (consensus) error grid analysis (EGA) and rate EGA of the plateaus and transition
      periods, respectively, yielded 86.8% and 68.6% accurate results (zone A) and
      12.1% and 20.0% benign errors (zone B). Continuous EGA yielded 88.5%, 75.4%, and
      79.3% accurate results and 8.3%, 14.3%, and 2.4% benign errors for the
      euglycemic, hyperglycemic, and hypoglycemic transition periods, respectively.
      Adverse events were mild and unlikely to be device related. CONCLUSION: This
      novel CGM system was safe and accurate across the clinically relevant glucose
      range.

PMID- 21880227
TI  - Real-life utilization of real-time continuous glucose monitoring: the complete
      picture.
AB  - BACKGROUND: Very few studies to date have analyzed the reasons why some people do
      not use real-time continuous glucose monitoring (RT-CGM) continuously, especially
      given its positive glycemic outcomes, or choose not to wear it at all, even after
      learning about its benefits. METHODS: A questionnaire was designed to assess real
      life use of and issues surrounding RT-CGM. Hemoglobin A1c (HbA1c) and duration of
      sensor use were also obtained from the patients' charts. RESULTS: Fifty-eight
      subjects with type 1 diabetes (T1DM), average age 15.0 +/- 4.8 years, T1DM
      duration 5.7 +/- 3.8 years, HbA1c 8.8 +/- 2.1%, 50% with RT-CGM, were included in
      the analysis. Hemoglobin A1c was lower with increased RT-CGM use. Real-time
      continuous glucose monitoring was ordered to improve control. Users liked the
      continuous data. The most disliked part was pain and discomfort. Occasional users
      described RT-CGM as annoying, a hassle, and interfering with their lives. Reasons
      for discontinuing RT-CGM included problematic equipment and inaccuracy (64%),
      intrusion in life (36%), and insurance issues (29%). Twenty-one percent of
      nonusers reported RT-CGM to be inconvenient or a hassle or just did not want it.
      Fifty-two percent of subjects continue to use RT-CGM despite reported problems.
      CONCLUSION: Real-time continuous glucose monitoring is a beneficial tool for
      improving glycemic control, and many use it despite reported problems and hassles
      with current devices. However, this technology has not been wholeheartedly
      embraced by many individuals with T1DM, especially in youngsters, because of
      issues mentioned here. Based on the findings of this study, it is hoped that
      improvements will be made to RT-CGM technology so that more people with diabetes
      will embrace this beneficial tool.

PMID- 21880228
TI  - Characterizing blood glucose variability using new metrics with continuous
      glucose monitoring data.
AB  - OBJECTIVE: Glycemic variability contributes to oxidative stress, which has been
      linked to the pathogenesis of the long-term complications of diabetes. Currently,
      the best metric for assessing glycemic variability is mean amplitude of glycemic
      excursion (MAGE); however, MAGE is not in routine clinical use. A glycemic
      variability metric in routine clinical use could potentially be an important
      measure of overall glucose control and a predictor of diabetes complication risk
      not detected by glycosylated hemoglobin (A1C) levels. This study aimed to develop
      and evaluate new automated metrics of glycemic variability that could be
      routinely applied to continuous glucose monitoring (CGM) data to assess and
      enhance glucose control. METHOD: Individual 24 h CGM tracings from our clinical
      diabetes research database were scored for MAGE and two additional metrics
      designed to compensate for aspects of variability not captured by MAGE: (1)
      number of daily glucose fluctuations >75 mg/dl that leave the normal range (70
      175 mg/dl), or excursion frequency, and (2) total daily fluctuation, or distance
      traveled. These scores were used to train machine learning algorithms to
      recognize excessive variability based on physician ratings of daily CGM charts,
      producing a third metric of glycemic variability: perceived variability. Finger
      stick A1C (average) and serum 1,5-anhydroglucitol (postprandial) levels were used
      as clinical markers of overall glucose control for comparison. RESULTS: Mean
      amplitude of glycemic excursion, excursion frequency, and distance traveled did
      not adequately quantify the glycemic variability visualized by physicians who
      evaluated the daily CGM plots. A naive Bayes classifier was developed that
      characterizes CGM tracings based on physician interpretations of tracings.
      Preliminary results suggest that the number of excessively variable days, as
      determined by this naive Bayes classifier, may be an effective way to
      automatically assess glycemic variability of CGM data. This metric more closely
      reflects 90-day changes in serum 1,5-anhydroglucitol levels than does MAGE.
      CONCLUSION: We have developed a new automated metric to assess overall glycemic
      variability in people with diabetes using CGM, which could easily be incorporated
      into commercially available CGM software. Additional work to validate and refine
      this metric is underway. Future studies are planned to correlate the metric with
      both urinary 8-iso-prostaglandin F2 alpha excretion and serum 1,5-anhydroglucitol
      levels to see how well it identifies patients with high glycemic variability and
      increased markers of oxidative stress to assess risk for long-term complications
      of diabetes.

PMID- 21880229
TI  - Creation of the Web-based University of Chicago Monogenic Diabetes Registry:
      using technology to facilitate longitudinal study of rare subtypes of diabetes.
AB  - BACKGROUND: Monogenic diabetes is a group of disorders caused by mutations in any
      one of a number of genes. Although a monogenic diagnosis--estimated to represent
      as much as 2% of all diabetes patients--can have a transformational impact on
      treatment, the majority of monogenic cases remain unidentified and little is
      known about their natural history. We thus created the first United States
      Monogenic Diabetes Registry (http://www.kovlerdiabetescenter.org/registry/) for
      individuals with either neonatal diabetes diagnosed before 1 year of age or with
      a phenotype suggestive of maturity-onset diabetes of the young. METHODS:
      Inclusion criteria and consent documents are viewable on our Web site, which
      allows secure collection of contact information to facilitate telephone consent
      and enrollment. Relevant medical, family, and historical data are collected
      longitudinally from a variety of sources and stored in our Web-accessible secure
      database. RESULTS: We have enrolled well over 700 subjects in the registry so
      far, with steady recruitment of those diagnosed under 1 year of age and
      increasing enrollment of those diagnosed later in life. Initially, participants
      were mostly self-referred but are increasingly being referred by their
      physicians. Comprehensive survey and medical records data are collected at
      enrollment, with ongoing collection of longitudinal data. Associated private
      Facebook and email discussion groups that we established have already fostered
      active participation. CONCLUSIONS: Our early success with the Monogenic Diabetes
      Registry demonstrates the effectiveness of low-cost Web-based tools, including
      surveys, the Research Electronic Data Capture database program, and discussion
      groups, for efficient enrollment and support of rare patients, and collection and
      maintenance of their data.

PMID- 21880230
TI  - A 16-week open-label, multicenter pilot study assessing insulin pump therapy in
      patients with type 2 diabetes suboptimally controlled with multiple daily
      injections.
AB  - BACKGROUND: We assessed the efficacy, safety, and patient-reported outcomes
      (PROs) of insulin pump therapy in patients with type 2 diabetes mellitus (T2DM)
      who were suboptimally controlled with a multiple daily injection (MDI) regimen.
      METHODS: In this subanalysis of a 16-week multicenter study, 21 insulin-pump
      naive patients [age 57 +/- 13 years, hemoglobin A1c (A1C) 8.4 +/- 1.0%, body
      weight 98 +/- 20 kg, total daily insulin dose 99 +/- 65 U, mean +/- standard
      deviation] treated at baseline with MDI therapy with or without oral antidiabetic
      agents discontinued all diabetes medications except metformin and initiated
      insulin pump therapy. Insulin was titrated to achieve the best possible glycemic
      control with the simplest possible dosing regimen. Outcome measures included A1C,
      fasting and postprandial glucose, body weight, incidence of hypoglycemia, and
      PROs. RESULTS: Glycemic control improved significantly after 16 weeks: A1C 7.3 +/
      1.0% (-1.1 +/- 1.2%, p < .001), fasting glucose 133 +/- 33 mg/dl (-32 +/- 74
      mg/dl, p < .005), and postprandial glucose 153 +/- 35 mg/dl (-38 +/- 46 mg/dl, p
      < .001). At week 16, the mean daily basal, bolus, and total insulin doses were 66
      +/- 36, 56 +/- 40, and 122 +/- 72 U (1.2 U/kg), respectively, and 90% of patients
      were treated with two or fewer daily basal rates. Body weight increased by 2.8 +/
      2.6 kg (p < .001). Mild hypoglycemia was experienced by 81% of patients at least
      once during the course of the study with no episodes of severe hypoglycemia.
      There were significant improvements in PRO measures. CONCLUSIONS: Insulin pump
      therapy using a relatively simple dosing regimen safely improved glucose control
      and PROs in patients with T2DM who were unable to achieve glycemic targets with
      MDI therapy. Controlled trials are needed to further assess the clinical benefits
      and cost-effectiveness of insulin pumps in this patient population.

PMID- 21880231
TI  - Hypoglycemia impairs quality of blood glucose simulation in a clinical decision
      support system.
AB  - BACKGROUND: Clinical decision support systems allow for decisions based on blood
      glucose simulations. The DiasNet simulation tool is based on accepted principles
      of physiology and simulates blood glucose concentrations accurately in type 1
      diabetes mellitus (T1DM) patients during periods without hypoglycemia, but
      deviations appear after hypoglycemia, possibly because of the long-term glucose
      counter-regulation to hypoglycemia. The purpose of this study was to evaluate the
      impact of hypoglycemia on blood glucose simulations. METHOD: Continuous glucose
      monitoring (CGM) data and diary data (meals, insulin, self-monitored blood
      glucose) were collected for 2 to 5 days from 17 T1DM patients with poor glycemic
      control. Hypoglycemic episodes [CGM glucose <63 mg/dl (3.5 mmol/liter) for >=20
      min] were identified in valid (well-calibrated) CGM data. For 24 hours after each
      hypoglycemic episode, a simulated (DiasNet) glucose profile was compared to the
      CGM glucose. RESULTS: A total of 52 episodes of hypoglycemia were identified in
      valid data. All subjects had at least one hypoglycemic episode. Ten episodes of
      hypoglycemia from nine subjects were eligible for analysis. The CGM glucose was
      significantly (p < .05) higher than simulated blood glucose for a period of 13 h,
      beginning 8 h after hypoglycemia onset. CONCLUSIONS: The present data show that
      hypoglycemia introduces substantial and systematic simulation errors for up to 24
      h after hypoglycemia. This underlines the need for further evaluation of
      mechanisms behind this putative long-term glucose counter-regulation to
      hypoglycemia. When using blood glucose simulations in decision support systems,
      the results indicate that simulations for several hours following a hypoglycemic
      event may underestimate glucose levels by 100 mg/dl (5.6 mmol/liter) or more.

PMID- 21880232
TI  - A stepwise approach toward closed-loop blood glucose control for intensive care
      unit patients: results from a feasibility study in type 1 diabetic subjects using
      vascular microdialysis with infrared spectrometry and a model predictive control
      algorithm.
AB  - BACKGROUND: Glycemic control can reduce the mortality and morbidity of intensive
      care patients. The CLINICIP (closed-loop insulin infusion for critically ill
      patients) project aimed to develop a closed-loop control system for this patient
      group. Following a stepwise approach, we combined three independently tested
      subparts to form a semiautomatic closed-loop system and evaluated it with respect
      to safety and performance aspects by testing it in subjects with type 1 diabetes
      mellitus (T1DM) in a first feasibility trial. METHODS: Vascular microdialysis, a
      multianalyte infrared spectroscopic glucose sensor, and a standard insulin
      infusion pump controlled by an adaptive model predictive control (MPC) algorithm
      were combined to form a closed-loop device, which was evaluated in four T1DM
      subjects during 30-hour feasibility studies. The aim was to maintain blood
      glucose concentration in the target range between 80 and 110 mg/dl. RESULTS: Mean
      plasma glucose concentration was 110.5 +/- 29.7 mg/dl. The MPC managed to
      establish normoglycemia within 105 +/- 78 minutes after trial start and managed
      to maintain glucose concentration within the target range for 47% of the time.
      The hyperglycemic index averaged to 11.9 +/- 5.3 mg/dl. CONCLUSION: Data of the
      feasibility trial illustrate the device being effective in controlling glycemia
      in T1DM subjects. However, the monitoring part of the loop must be improved with
      respect to accuracy and precision before testing the system in the target
      population.

PMID- 21880233
TI  - The Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study:
      methodological details.
AB  - BACKGROUND: Currently available estimates of diabetes prevalence in India are
      based on published data derived from very few studies. The Indian Council of
      Medical Research-India Diabetes (ICMR-INDIAB) study is a community-based survey
      conceived with the aim of obtaining the prevalence rates of diabetes in India as
      a whole, covering all 28 states, the National Capital Territory of Delhi, and two
      of the union territories in the mainland of India, with a total sample size of
      124,000 individuals. METHODS: A stratified multistage sampling design has been
      used. In all study subjects, a structured questionnaire was administered and
      anthropometric parameters and blood pressure were measured. Fasting capillary
      blood glucose was first determined using a glucose meter. An oral glucose load
      was then administered to all subjects except those with self-reported diabetes,
      and the 2 h post-load capillary blood glucose was estimated. In every fifth
      subject, a fasting venous sample was collected for measurement of lipids and
      creatinine, a resting 12-lead electrocardiogram was performed, and dietary
      assessment questionnaire was administered. In all diabetic subjects, an
      additional diabetes questionnaire was used and a fasting venous sample drawn for
      glycated hemoglobin. RESULTS: All biological samples collected were analyzed in a
      central laboratory. All data collected were stored electronically. Quality
      control was achieved through multiple tiers of checks. CONCLUSIONS: The ICMR
      INDIAB study is the first of its kind attempting to provide accurate and
      comprehensive state- and national-level data on diabetes prevalence in India.

PMID- 21880234
TI  - Analysis of the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB)
      study.
AB  - The Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study is the
      first nationally representative survey of diabetes in India. It aims to provide
      national and regional counts of diabetes and prediabetes and also of
      cardiovascular risk factors. This ambitious and complex survey uses robust
      sampling techniques, standardized methods, appropriate quality assurance, and a
      three-phase data collection. However, the survey should be completed within a
      reasonable time span to avoid a differential effect of secular trends on regional
      estimates. A high response rate and low missing values must also be ensured.
      Reliance on capillary whole blood glucose (CBG) for the diagnosis of
      hyperglycemic states is a limitation of the survey. However, this is a reasonable
      compromise given the practical challenges of such a large study. Despite a good
      correlation between CBG and venous plasma glucose (VPG), the use of CBG may
      misclassify glycemic status. A better characterization of the CBG-VPG
      relationship, and the performance of CBG for detecting hyperglycemia, using a
      much larger sample, seems therefore advisable. This should be possible given that
      venous blood has been collected on a sizeable subset of participants. The Indian
      Council of Medical Research and the Madras Diabetes Research Foundation deserve
      praise for this massive undertaking, which will highlight areas for policy action
      and establish a national framework for noncommunicable disease (NCD)
      surveillance. The ICMR-INDIAB survey lays the foundation for effective NCD
      prevention and control and for applied public health research.

PMID- 21880235
TI  - Convergence of prevalence rates of diabetes and cardiometabolic risk factors in
      middle and low income groups in urban India: 10-year follow-up of the Chennai
      Urban Population Study.
AB  - AIM: The aim of this study was to look for temporal changes in the prevalence of
      diabetes and cardiometabolic risk factors in two residential colonies in Chennai.
      METHODS: Chennai Urban Population Study (CUPS) was carried out between 1996-1998
      in Chennai in two residential colonies representing the middle income group (MIG)
      and lower income group (LIG), respectively. The MIG had twice the prevalence rate
      of diabetes as the LIG and higher prevalence rates of hypertension, obesity, and
      dyslipidemia. They were motivated to increase their physical activity, which led
      to the building of a park. The LIG was given standard lifestyle advice. Follow-up
      surveys of both colonies were performed after a period of 10 years. RESULTS: In
      the MIG, the prevalence of diabetes increased from 12.4 to 15.4% (24% increase),
      while in the LIG, it increased from 6.5 to 15.3% (135% increase, p < .001). In
      the LIG, the prevalence rates of central obesity (baseline vs follow-up, male:
      30.8 vs 50.9%, p < .001; female: 16.9 vs 49.8%, p < .001), hypertension (8.4 vs
      20.1%, p < .001), hypercholesterolemia (14.2 vs. 20.4%, p < .05), and
      hypertriglyceridemia (8.0 vs 23.5%, p < .001) significantly increased and became
      similar to that seen in the MIG. CONCLUSION: There is a rapid reversal of
      socioeconomic gradient for diabetes and cardiometabolic risk factors in urban
      India with a convergence of prevalence rates among people in the MIG and LIG.
      This could have a serious economic impact on poor people in developing countries
      such as India.

PMID- 21880236
TI  - Diabetes and Technology for Increased Activity (DaTA) study: results of a remote
      monitoring intervention for prevention of metabolic syndrome.
AB  - OBJECTIVE: An increasingly aged, overweight, and sedentary population has
      resulted in elevated risk of cardiovascular disease (CVD). The escalating
      incidence of diabetes and other chronic illnesses, deficits in health care
      budgets, and physician shortages, especially in rural communities, have prompted
      investigations of feasible solutions. The Diabetes and Technology for Increased
      Activity (DaTA) study was designed to test the effectiveness of a lifestyle
      intervention driven by self-monitoring of blood glucose (BG), blood pressure
      (BP), physical activity (PA), and weight to positively impact CVD risk factors in
      a medically underserviced rural population with a high incidence of metabolic
      syndrome (MS). RESEARCH DESIGN AND METHODS: Conducted in a community-based
      research setting, this single-center open feasibility study used smart phones to
      transmit BP, BG, pedometer, weight, heart rate, and activity measurements to a
      database. Technology allowed participants to interface with the clinical team and
      self-monitor their personal health indicators. RESULTS: Twenty-four participants
      aged 30 to 71 years completed the 8-week intervention. Participants had
      significant improvement in clinic (p = .046) and self-monitored diastolic BP (p =
      .001), body mass index (p = .002), and total cholesterol (p = .009), and steps
      per day. Daily PA increased as well as participants' interest in and willingness
      to make lifestyle changes that impact health outcomes. CONCLUSIONS: The DaTA
      study demonstrated that self-monitoring of the risk factors for MS and increased
      PA improved the participant's CVD risk profile. Considering the 8-week time
      period of this intervention, results are encouraging. This lifestyle
      intervention, which uses education and technology as tools, confirms the utility
      of remote health monitoring.

PMID- 21880237
TI  - Remote monitoring technologies for the prevention of metabolic syndrome: the
      Diabetes and Technology for Increased Activity (DaTA) study.
AB  - OBJECTIVES: Remote monitoring technologies are ideally suited for rural
      communities with limited access to health care. In an 8-week pilot study, we
      examined the feasibility of implementing and conducting a technology-intensive
      intervention in an underserviced rural setting. Our goal was to test the utility
      of self-monitoring technologies, physical activity, and education as tools to
      manage health indicators for the development of the cardiovascular complications
      (CVCs) of type 2 diabetes. RESEARCH DESIGN AND METHODS: The Diabetes and
      Technology for Increased Activity study was an open single-center study conducted
      in a community-based research setting. All 24 participants were provided with a
      BlackberryTM Smartphone, blood pressure monitor, glucometer, and pedometer.
      Smartphones transmitted measurements and survey results to the database,
      interfaced participants with the clinical team, and allowed for self-monitoring.
      RESULTS: Outcomes were improved body composition, improved markers of CVC risk
      factors, increased daily exercise, and interest in or awareness of lifestyle
      changes that impact health outcomes. Participants had excellent compliance for
      measurements, as self-monitoring provided a sense of security that improved from
      week 4 to week 8. CONCLUSIONS: Our team gained substantial insight into the
      operational requirements of technology-facilitated health care, including
      redefined hours of service; data reporting, management, and access protocols; and
      the utility of real-time clinical measures by remote monitoring. We developed an
      understanding of knowledge translation strategies as well as successful
      motivational and educational tools. Importantly, remote monitoring technology was
      found to be feasible and accepted in a rural setting.

PMID- 21880238
TI  - The use of optical coherence tomography to determine the effect of
      thiazolidinediones on retinal thickness in patients with type 2 diabetes.
AB  - OBJECTIVE: Thiazolidinediones (TZDs) are insulin-sensitizing agents that are
      associated with peripheral edema and have been reported to be associated with
      diabetic macular edema (DME). We hypothesized that TZDs produce subclinical
      increases in retinal thickness that may be detected by optical coherence
      tomography (OCT) but are not seen on routine dilated funduscopic examination.
      RESEARCH DESIGN AND METHODS: We used OCT to screen for subclinical DME in a cross
      sectional study of patients with type 2 diabetes; 29 patients were taking TZDs
      and 58 were not taking TZDs. We analyzed data using multiple linear regression
      analysis to investigate associations of retinal thickness with clinical
      characteristics. RESULTS: There was no significant difference between the central
      subfield retinal thickness in the non-TZD group (206.4 +/- 28.0 microns; n = 59)
      and TZD group (204.1 +/- 26.1 microns; n = 29) (p = .72) nor were there
      significant differences in any other retinal subfield. There was no significant
      correlation of retinal thickness with laboratory results studies--peripheral
      edema, gender, age, duration of diabetes, individual, or combinations of
      medications. Retinal thickness differences between regions displayed normal
      anatomical variation. However, ethnic differences were found in which African
      Americans had thinner retinas in all regions than Caucasians regardless of
      whether or not they used TZDs. CONCLUSIONS: These data suggest that TZDs do not
      cause subclinical DME in a demographically diverse patient population with
      diabetes. The established normal ranges for macular thickness may require
      adjustment based on ethnicity.

PMID- 21880239
TI  - Efficacy of continuous glucose monitoring in improving glycemic control and
      reducing hypoglycemia: a systematic review and meta-analysis of randomized
      trials.
AB  - OBJECTIVE: We conducted a systematic review and meta-analysis to assess the
      efficacy of continuous glucose monitoring (CGM) in improving glycemic control and
      reducing hypoglycemia compared to self-monitored blood glucose (SMBG). METHODS:
      We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and Scopus for
      randomized trials of adults and children with type 1 or type 2 diabetes mellitus
      (T1DM or T2DM). Pairs of reviewers independently selected studies, assessed
      methodological quality, and extracted data. Meta-analytic estimates of treatment
      effects were generated using a random-effects model. RESULTS: Nineteen trials
      were eligible and provided data for meta-analysis. Overall, CGM was associated
      with a significant reduction in mean hemoglobin A1c [HbA1c; weighted mean
      difference (WMD) of -0.27% (95% confidence interval [CI] -0.44 to -0.10)]. This
      was true for adults with T1DM as well as T2DM [WMD -0.50% (95% CI -0.69 to -0.30)
      and -0.70 (95% CI, -1.14 to -0.27), respectively]. No significant effect was
      noted in children and adolescents. There was no significant difference in HbA1c
      reduction between studies of real-time versus non-realtime devices (WMD -0.22%,
      95% CI, -0.59 to 0.15 versus -0.30%, 95% CI, -0.49 to -0.10; p for interaction
      0.71). The quality of evidence was moderate due to imprecision, suggesting
      increased risk for bias. Data for the incidence of severe or nocturnal
      hypoglycemia were sparse and imprecise. In studies that reported patient
      satisfaction, users felt confident about the device and gave positive reviews.
      CONCLUSION: Continuous glucose monitoring seems to help improve glycemic control
      in adults with T1DM and T2DM. The effect on hypoglycemia incidence is imprecise
      and unclear. Larger trials with longer follow-up are needed to assess the
      efficacy of CGM in reducing patient-important complications without significantly
      increasing the burden of care for patients with diabetes.

PMID- 21880240
TI  - Lancing: quo vadis?
AB  - Today, lancing fingertips or alternative sites for obtaining a blood sample for
      self-monitoring of blood glucose (SMBG) is a standard procedure for most patients
      with diabetes. The need for frequent lancing and associated discomfort and pain
      can be seen as a key hurdle for patients to comply with SMBG regimens. This
      article provides an overview of the status quo and future of lancing, focusing on
      key areas for future developments driven by customer and market needs. We also
      review technical issues and provide a background for possible improvements. The
      act of puncturing the skin with a lancet to obtain a blood sample seems to remain
      the standard procedure for the foreseeable future, because alternate ways of
      providing a blood sample have not demonstrated overall superiority (e.g., with
      laser technology). Other methods, which avoid lancing entirely, have also not
      gained broad market acceptance (e.g., minimally invasive continuous glucose
      monitoring) or not shown technical viability (e.g., noninvasive glucose
      monitoring). In relation to blood glucose (BG) meters and test strips, lancing
      has been a "stepchild" with regards to commercial attention and development
      efforts. Nevertheless, significant technological improvements have been made in
      this field to address key customer needs, including better performance (regarding
      pain, wound healing, and long-term sensitivity), reduced cost, and higher
      integration with other components of BG monitoring (e.g., integration of the
      lancing device with the glucose monitor). From a technical perspective, it is
      apparent that highly comfortable lancing can be accomplished; however, this still
      requires fairly advanced and complex devices. New developments are necessary to
      achieve this level of sophistication and performance with less intricate and
      costly system designs. Manufacturers' motivation to pursue these developments is
      compromised by the fact that they might not recoup their development cost on
      commercial advanced lancing systems through direct profits, but only through its
      positive influence on adherence and increased more profitable sensor utilization.
      We believe that two main driving forces will continue to push the evolution of
      lancing and sampling technology: (1) the need for maximum lancing comfort and (2)
      the advent of fully integrated systems, realizing a device in which all steps for
      SMBG are incorporated, thus providing a "one-step" experience. Rendering lancing
      a "nonissue" will eliminate a key barrier to adherence with appropriate SMBG
      regimens. Providing sophisticated lancing devices that allow the highest level of
      comfort and/or seamless blood sampling is key to improving user acceptance. This
      may have a greater impact on metabolic control than many of the new and expensive
      antidiabetic drugs.

PMID- 21880241
TI  - High sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-6,
      and vascular cell adhesion molecule-1 levels in Asian Indians with metabolic
      syndrome and insulin resistance (CURES-105).
AB  - AIM: The aim of this study was to assess levels of high-sensitivity C-reactive
      protein (hs-CRP), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6),
      and vascular cell adhesion molecule-1 (VCAM-1) in South Indian subjects with and
      without MS and among MS subjects with and without insulin resistance (IR).
      METHODOLOGY: From the population-based Chennai Urban Rural Epidemiology Study,
      334 subjects with MS and 342 subjects without MS were selected. Metabolic
      syndrome was diagnosed based on modified National Cholesterol Education Program
      criteria. High-sensitivity C-reactive protein, TNF-alpha, IL-6, and VCAM-1 were
      measured by enzyme-linked immunosorbent assay. Insulin resistance was calculated
      using the homeostasis model assessment (HOMA-IR) using the following formula:
      fasting insulin (uIU/ml) * fasting glucose (mmol/liter)/22.5. RESULTS: Subjects
      with MS had significantly higher levels of all four inflammatory markers compared
      to those without MS: hs-CRP (2.57 vs 2.19 mg/liter) (p < .05), TNF-alpha (4.47 vs
      3.89 pg/ml) (p < .05), IL-6 (16.22 vs 10.96 pg/ml) (p < .05), and VCAM-1 (13.8 vs
      7.94 pg/ml) (p < .05). In the total study subjects, hs-CRP (r = 0.089, p = .047),
      TNF-alpha (r = 0.113, p = .040), IL-6 (r = 0.176, p = .042), and VCAM-1 (r =
      0.230, p = .06) were significantly correlated with MS. With increasing quartiles
      of IR, mean levels of hs-CRP (p for trend <.001) and TNF-alpha (p for trend <.05)
      increased linearly. MS subjects with IR had higher levels of hs-CRP (p < .001)
      and TNF-alpha (p < .05) compared to MS subjects without IR. CONCLUSION: In Asian
      Indians, inflammatory cytokines hs-CRP, TNF-alpha, IL-6, and VCAM-1 are elevated
      in subjects with MS while hs-CRP and TNF-alpha are further elevated in those with
      MS and IR.

PMID- 21880242
TI  - Effect of pioglitazone and ramipril on biomarkers of low-grade inflammation and
      vascular function in nondiabetic patients with increased cardiovascular risk and
      an activated inflammation: results from the PIOace study.
AB  - AIMS: This study investigated the effects of pioglitazone (PIO), ramipril (RAM),
      or their combination (PIRA) on low-grade inflammation in nondiabetic hypertensive
      patients with increased cardiovascular risk. METHODS AND RESULTS: Patients
      enrolled in this placebo-controlled, double-blind, randomized, parallel trial (72
      male, 77 female, aged 60 +/- 9 years, body mass index 30.4 +/- 4.7 kg/m(2),
      duration of hypertension 9 +/- 8 years) were treated with either 30/45 mg PIO
      (dose titration), 2.5/5 mg RAM, or their combination for 12 weeks. A reduction in
      high-sensitivity C-reactive protein was observed with PIO (-0.89 +/- 1.98
      mg/liter; -25%) and PIRA (-0.49 +/- 2.11 mg/liter; -16%), while an increase was
      seen with RAM (0.58 +/- 2.13 mg/liter; +20%, p < .05 vs PIO and PIRA). The 24
      hour blood pressure profile showed a small increase with both monotherapies but a
      decrease with PIRA (p < .05 vs PIO). Improvements in biomarkers of chronic
      systemic inflammation and insulin resistance (IR) were observed in the PIO and
      PIRA arms only [PIO/RAM/PIRA: homeostasis model of assessment of IR: -0.78 +/-
      1.39 (-29%)/0.15 +/- 1.03 (+5%)/ -1.44 +/- 2.83 (-40%); adiponectin: 8.51 +/-
      5.91 (+104%)/ 0.09 +/- 2.63 (+1%)/ 8.86 +/- 6.37 mg/liter (+107%); matrix metallo
      proteinase-9: -48 +/- 127 (-12%)/-1 +/- 224 (0%)/-60 +/- 210 ng/ml (-13%), p <
      .05 for RAM vs PIO or PIRA in all cases]. CONCLUSIONS: Our 3-month study in
      nondiabetic hypertensive patients showed a decrease in biomarkers of IR and
      chronic systemic inflammation with the PIO monotherapy and the PIRA combination
      only, which may help to explain some findings in other cardiovascular outcome
      trials.

PMID- 21880243
TI  - Outcome measures for outpatient hypoglycemia prevention studies.
AB  - Systems are being developed that utilize algorithms to predict impending
      hypoglycemia using commercially available continuous glucose monitoring (CGM)
      devices and to discontinue insulin delivery if hypoglycemia is predicted. In
      outpatient studies designed to test such systems, CGM-measured glycemic indices
      will not only be important outcome measures of efficacy but, in certain cases,
      will be the only good outcome. This is especially true in short-term studies
      designed to reduce hypoglycemia since the event rate for severe hypoglycemic
      events is too low for it to be a good outcome, and milder hypoglycemia often will
      be variably detected. Continuous glucose monitoring inaccuracy can be accounted
      for in the study design by increasing sample size and/or study duration.

PMID- 21880244
TI  - Nanotechnology in elevation of the worldwide impact of obesity and obesity
      related diseases: potential roles in human health and disease.
AB  - Current worldwide data show epidemics of obesity and type 2 diabetes with no real
      solutions apart from continuous calls to changing lifestyle and food habits.
      Despite health messages that are communicated by health authorities, the epidemic
      is growing. More people are affected with health consequences that are usually
      frightening as more resources are wasted, especially in areas where health care
      and resources are lacking. Nanotechnology applications in food industry present
      practical approaches that help produce more tasty food with little calories,
      functional foods, and nutritional supplements and alter the fats and sugar
      contents of our foods with potential for many more applications. Consequently,
      this opens more windows to better control of many nutritional deficiencies as
      well as obesity and type 2 diabetes, especially among children and young adults
      who are addicted to fast food. With such potential, food producers, policy
      makers, health authorities, food scientists, and governments need to collaborate
      and make all possible efforts to fund and support research in different areas of
      food produced using nanotechnology. So far, consumers are not prepared to accept
      food produced using nanotechnology, mainly because information on the safety of
      such products are not enough. This issue needs to be addressed and researched
      well using suitable risk assessment methodologies. Consumers need to be assured,
      and involved as well, to avoid the "refusal state" that still exists against many
      safe products such as genetically modified organisms and irradiated food. There
      is the possibility that consumers could perceive that they will bear the
      potential risks posed by nanotechnology applications while the benefits will
      accrue mainly to others, such as food processors or farmers.

PMID- 21880245
TI  - Accuracy of the CONTOUR(r) blood glucose monitoring system.
AB  - OBJECTIVE: The aim of the study was to assess the accuracy of the CONTOUR(r)
      blood glucose monitoring system (BGMS) according to the International
      Organization for Standardization's International Standard 15197 (ISO 15197:2003)
      guidelines and to more stringent criteria. METHOD: Finger stick blood samples
      from 105 subjects with diabetes (25 with type 1, 77 with type 2, and 3 with type
      unknown) were tested using the CONTOUR BGMS and YSI glucose analyzer. RESULTS:
      99.3% of results were within ISO 15197:2003 criteria (+/-15 mg/dl of YSI results
      at glucose concentrations <75 mg/dl and +/-20% at glucose concentrations >=75
      mg/dl). Additionally, 96.7% of results were accurate according to more stringent
      criteria (+/-15 mg/dl of YSI results for glucose concentrations <100 mg/dl and +/
      15% for glucose concentrations >=100 mg/dl). Error grid analysis showed that
      99.3% and 0.7% of results were within zones A and B, respectively. CONCLUSION:
      The CONTOUR BGMS exceeded both the minimum acceptable accuracy based on ISO
      15197:2003 and the more stringent accuracy criteria.

PMID- 21880246
TI  - Preanalytic and analytic accuracy: toward more realistic and meaningful self
      monitoring of blood glucose submissions for regulatory approval.
AB  - Dr. Cembrowski provides an analysis of an article by Harrison and colleagues in
      this issue of Journal of Diabetes Science and Technology in which the authors
      describe the evaluation of a new device for self-monitoring of blood glucose, the
      Bayer CONTOUR(r) blood glucose monitoring system.

PMID- 21880247
TI  - Use of U-500 regular insulin via continuous subcutaneous insulin infusion:
      clinical practice experience.

PMID- 21880249
TI  - [Cell cannibalism by entosis: a new pathway leading to aneuploidy in cancer].

PMID- 21880248
TI  - [Olfaction : the cortex reshuffles the maps].

PMID- 21880250
TI  - [Homozygous deletion of DPY19L2 is responsible for most cases of
      globozoospermia].

PMID- 21880251
TI  - [A modular and non pathogenic type A botulinum toxin].

PMID- 21880252
TI  - [TIF1gamma: a tumor suppressor gene in chronic myelomonocytic leukemia].

PMID- 21880253
TI  - [TIF1gamma is a chief conductor of the hematopoietic system].

PMID- 21880254
TI  - [Follow-up of the children born by ICSI].

PMID- 21880255
TI  - [Chemotaxis of spermatozoa is regulated by progesterone binding on calcium
      channel CATSPER].

PMID- 21880256
TI  - [miR-122, a microRNA gatekeeper of iron homeostasis].

PMID- 21880257
TI  - [Genome: does a paucity of initiation events lead to fragility?].

PMID- 21880258
TI  - [3D revolution of stem cells: building a retina in vitro].

PMID- 21880259
TI  - [Microglia arise from extra-embryonic yolk sac primitive progenitors].
AB  - Microglia are the resident macrophage population of the central nervous system
      (CNS). Adequate microglia function is crucial for the homeostasis of the CNS in
      health and disease, as they represent the first line of defence against
      pathogens, contributing to immune responses, but are also involved in tissue
      repair and remodeling. It is therefore crucial to better understand microglia
      origin and homeostasis. Much controversy remains regarding the nature of
      microglial progenitors, as the exact contribution and persistence of embryonic
      and post-natal hematopoietic progenitors to the adult microglial pool in the
      steady state remained unclear. In this study, we show that post-natal
      hematopoietic progenitors do not significantly contribute to microglia
      homeostasis in the adult brain in mice. In vivo lineage tracing studies
      established that adult microglia derives from primitive hematopoietic progenitors
      that arise before embryonic day 8. These results identify microglia as an
      ontogenically distinct population in the mononuclear phagocyte system and have
      implications for the use of embryonically-derived microglial progenitors for the
      treatment of various brain disorders.

PMID- 21880261
TI  - [Alzheimer's disease, amyloid peptide and synaptic dysfunction].
AB  - Alzheimer's disease (AD) is the first cause of dementia that leads to insidious
      and progressive loss of memory and cognitive functions. In the early stages of
      AD, there is a strong correlation between memory impairment and cortical levels
      of soluble amyloid-beta peptide oligomers (Abeta). It has become clear that Abeta
      disrupt glutamatergic synaptic function, which in turn may lead to the
      characteristic cognitive deficits. Conversely, experiments in rodents have
      conforted the notion that Abetao impairs synaptic transmission and plasticity,
      and that mouse models with increased production of these oligomers display
      cognitive impairment. Many studies have attempted to determine the mechanisms by
      which Abetao disrupt synaptic plasticity and mediate their detrimental effect,
      but the actual pathways are still poorly understood. Here we review this thriving
      area of research which aims at understanding the mechanisms of synaptic
      dysfunction in the early phase of AD, and its consequences on the activity of
      neural circuits.

PMID- 21880260
TI  - [Histone methyltransferases: a new class of therapeutic targets in cancer
      treatment?].
AB  - Epigenetic gene regulation contributes, together with genetic alterations, to
      cancer development and progression. In contrast to genetic disorders, the
      possibility of reversing epigenetic alterations has provided original targets for
      therapeutic application. In the last years, work has been focused on the
      pharmacological restoration of epigenetic regulation balance using epidrugs which
      yield hopes for novel strategy in cancer therapy. Histone acetylation and DNA
      methylation are epigenetic modifications which have been closely linked to the
      pathology of human cancers, and inhibitors of both enzyme classes for clinical
      use are at hands. Novel findings accumulated during the last years both in
      chemistry and biomedical applications give rise to new targeted treatments
      against cancer. Since their links with pathogenesis and progression of cancer
      were recognized, histone methyltransferases emerge as promising therapeutic
      targets in cancer treatment.

PMID- 21880262
TI  - [Immunodeficiencies and pathologies associated with mutations in STIM/ORAI, a
      membrane complex in the heart of calcium signalling].
AB  - Six years ago, STIM1 (stromal interaction molecule 1) was identified as an
      essential component of store-operated calcium channels and in less than one year
      teamed up with its first partner ORAI1 in immune cells to reconstitute CRAC
      (calcium-release activated current) channel function. Since then, STIM1 and ORAI1
      have developed an ever increasing social network and to date are now linked to
      nine families of proteins involved in calcium signalling. As a result of this,
      STIM1 and ORAI1 are now involved in three separate calcium entry pathways, Icrac,
      Iarc (arachidonic regulated calcium current) and voltage-dependent channels.
      Physiopathological roles of STIM1 and ORAI1 were first described in the
      immunological system but, as main actors at the central node in the calcium
      signalling network, there are now clear evidences that mutations in genes coding
      STIM1 or ORAI1 interfere with several other diseases.

PMID- 21880263
TI  - [A uNick protein].
AB  - Nck is an adaptor protein composed of three N-terminal Src Homology (SH) 3
      domains followed by a unique C-terminal SH2 domain. Like other SH2/SH3 domains
      containing adaptor proteins, Nck mediates signal transduction from activated cell
      surface receptors by directing the flow of information to elicit properly
      orchestrated cell responses. In this way, Nck appears to be unique in its
      contribution to a wide variety of cellular processes. Moreover, in addition to
      the typical signal/pY-SH2/SH3-effectors mode of signaling, Nck also transduces
      signals through an inverse mode of -signaling (signal-SH3/SH2-pY/effectors) and
      from various cell compartments. Since Nck contributes to important morphogenic
      and mitogenic processes, deregulated expression of Nck could be detrimental to
      cellular homeostasis. In agreement, Nck expression has been found upregulated in
      numerous types of cancer. In this paper we delineate the main molecular 
      signaling -complexes associated with Nck, focusing on those involved in cancer
      progression.

PMID- 21880264
TI  - [Light-sheet based fluorescence microscopy: the dark side of the sample finally
      revealed].
AB  - Light-sheet based fluorescence microscopy (LSM) is an optical technique that
      becomes more and more popular for multi-view imaging of in vivo sample in its
      physiological environment. LSM combines the advantages of the direct optical
      sectioning to the ones of optical tomography by angular scanning. In fact, a thin
      light-sheet illuminates laterally a section of the sample, thus limiting the
      effects of photobleaching and phototoxicity only to the plane of interest. The
      spatial resolution can be improved by combining multiple views obtained along
      different angle into a single data, leading to a 3D isotropic rendering of the
      sample. Such an approach provides several advantages in comparison to
      conventional 3D microscopic techniques: confocal and multiphoton microscopies. It
      makes LSM an optical tool suited for imaging specimens with a subcellular
      resolution even inside an embryo and with temporal resolution adapted for real
      time monitoring of biological processes.

PMID- 21880265
TI  - [Neuroimaging and neuroscience of emotional processes].
AB  - In neurosciences, there is increasing interest in studying affective, emotional
      and social processes in humans and animals. What are the conceptual framework
      identified for these studies and the technical approaches undertaken? What
      information has already emerged from these studies? Which results have already
      been obtained and what are the researchers' goals? Can these neuroimaging
      analyses provide novel insights to improve our understanding of psychiatric
      disorders? These are some of the questions addressed in this concise overview of
      our knowledge in this domain.

PMID- 21880266
TI  - [Uncertainty of long term preservation of digital documents and how to cope with
      it].
AB  - The development of digital technologies in all activities sectors of our society
      leads to a growing number of digital documents. A significant part of these
      documents needs to be durably preserved. This long term preservation has to face
      the short life expectancy of the technologies and the digital storage media.
      Large national organizations have already take this problem into account and set
      up teams, skills and means to face this challenge. At the opposite, the small
      structures, doctor's offices, individuals, students, etc. are not generally aware
      of the problem or are stripped to face there. A certain number of simple actions,
      not requiring specific skills in data processing can nevertheless be undertaken.
      Without important expenditure, they increase to a significant degree, the
      security level of the documents over the long term.

PMID- 21880267
TI  - [Images in the dialogue between science and society].
AB  - In France, over 45 millions people watch TV every day for more than 3 hours.
      Science and image get well together since most TV watchers trust this media and
      rely on it (more than on any other source) for their scientific information. This
      emphasizes the power of images, which do not always deliver information, but can
      be naively regarded as creating communication. Image is necessary and an event
      which does not generate images is a non-event. Images are more than just a
      support for scientific messages: technologies have produced an enormous amount of
      images which allow us to uncover the mysteries of the world and Universe, their
      beauty and delicacy. We can be fascinated by the discovery of the invisible world
      which surrounds us, and science has truly generated artistic masterpieces even
      though we should remember that its primary goal is to understand the world rather
      than to create images.

PMID- 21880268
TI  - [The bewildering complexity of cancer].

PMID- 21880269
TI  - Thermodynamic stability of bacteriorhodopsin mutants measured relative to the
      bacterioopsin unfolded state.
AB  - The stability of bacteriorhodopsin (bR) has often been assessed using SDS
      unfolding assays that monitor the transition of folded bR (bR(f)) to unfolded
      (bR(u)). While many criteria suggest that the unfolding curves reflect
      thermodynamic stability, slow retinal (RET) hydrolysis during refolding makes it
      impossible to perform the most rigorous test for equilibrium, i.e.,
      superimposable unfolding and refolding curves. Here we made a new equilibrium
      test by asking whether the refolding rate in the transition zone is faster than
      RET hydrolysis. We find that under conditions we have used previously, refolding
      is in fact slower than hydrolysis, strongly suggesting that equilibrium is not
      achieved. Instead, the apparent free energy values reported previously are
      dominated by unfolding rates. To assess how different the true equilibrium values
      are, we employed an alternative method by measuring the transition of bR(f) to
      unfolded bacterioopsin (bO(u)), the RET-free form of unfolded protein. The bR(f)
      to-bO(u) transition is fully reversible, particular when we add excess RET. We
      compared the difference in unfolding free energies for 13 bR mutants measured by
      both assays. For 12 of the 13 mutants with a wide range of stabilities, the
      results are essentially the same within experimental error. The congruence of the
      results is fortuitous and suggests the energetic effects of most mutations may be
      focused on the folded state. The bR(f)-to-bO(u) reaction is inconvenient because
      many days are required to reach equilibrium, but it is the preferable measure of
      thermodynamic stability. This article is part of a Special Issue entitled:
      Protein Folding in Membranes.

PMID- 21880270
TI  - Taxing "Sin drinks": from economy to sugar control.

PMID- 21880271
TI  - Development of a genetic system for Marinobacter adhaerens HP15 involved in
      marine aggregate formation by interacting with diatom cells.
AB  - Diatom aggregation is substantial for organic carbon flux from the photic zone to
      deeper waters. Many heterotrophic bacteria ubiquitously found in diverse marine
      environments interact with marine algae and thus impact organic matter and energy
      cycling in the ocean. In particular, Marinobacter adhaerens HP15 induces
      aggregate formation while interacting with the diatom, Thalassiosira weissflogii.
      To study this effect at the molecular level, a genetic tool system was developed
      for strain HP15. The antibiotic susceptibility spectrum of this organism was
      determined and electroporation and conjugation protocols were established. Among
      various plasmids of different incompatibility groups, only two were shown to
      replicate in M. adhaerens. 1.4*10(-3) transconjugants per recipient were obtained
      for a broad-host-range vector. Electroporation efficiency corresponded to
      1.1*10(5)CFU per MUg of DNA. Transposon and gene-specific mutageneses were
      conducted for flagellum biosynthetic genes. Mutant phenotypes were confirmed by
      swimming assay and microscopy. Successful expression of two reporter genes in
      strain HP15 revealed useful tools for gene expression analyses, which will allow
      studying diverse bacteria-algae interactions at the molecular level and hence to
      gain a mechanistic understanding of micro-scale processes underlying ocean basin
      scale processes. This study is the first report for the genetic manipulation of a
      Marinobacter species which specifically interacts with marine diatoms and serves
      as model to additionally analyze various previously reported Marinobacter-algae
      interactions in depth.

PMID- 21880272
TI  - It's time to pay attention to the endometrium.
AB  - The physiologic importance of the endometrium in assisted reproductive technology
      is now receiving much research attention. The historical importance of ultrasound
      for determination of endometrial pattern, thickness and contractility is reviewed
      and speculation provided for a possible mechanism of the adverse effect of thin
      endometrium on implantation.

PMID- 21880273
TI  - Assessment of endometrial receptivity.
AB  - OBJECTIVE: To provide a focused review of the scientific literature pertaining to
      endometrial receptivity. DESIGN: Review of the literature and appraisal of
      relevant articles. SETTING: Academic teaching hospital. PATIENT(S): Women with
      infertility. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Critical review of
      the literature. RESULT(S): Although a consensus has been achieved regarding the
      existence of a temporally defined period during which embryo attachment and
      invasion can occur (called the "window of implantation"), reliable methods to
      assess "receptivity" have not been established or adequately validated. In women
      with certain gynecologic disorders, including endometriosis, tubal disease, and
      polycystic ovary syndrome, endometrial receptivity seems to be compromised,
      leading to infertility and pregnancy loss. The establishment of reliable
      biomarkers for the detection of defects in endometrial receptivity has been a
      long-sought goal that remains an elusive target. The validation of endometrial
      biomarkers will require properly designed and implemented studies based on the
      recognition that endometrial receptivity defects are not equally distributed in
      women with endometriosis or these other conditions. CONCLUSION(S): Rapidly
      advancing technologies are bringing new biomarkers to the clinical arena that
      promise to further reveal the complexities of the implantation process.

PMID- 21880274
TI  - Hormonal induction of endometrial receptivity.
AB  - OBJECTIVE: To review and synthesize information from the scientific literature
      pertaining to the hormonal induction of endometrial receptivity before ET.
      DESIGN: Critical review of selected scientific literature, synthesis and
      formulation of opinion. SETTING: Not applicable. PATIENT(S): Prospective
      recipients of oocyte donation or candidates for frozen embryo transfer.
      INTERVENTION(S): Hormonal treatment for the purpose of induction of endometrial
      receptivity. MAIN OUTCOME MEASURE(S): Successful induction of endometrial
      receptivity, as substantiated by live birth rates, pregnancy rates, implantation
      rates or by measuring putative markers of endometrial receptivity. RESULT(S): The
      practice of assisted reproductive technology, particularly third-party parenting,
      in which the source of oocytes is separated from the endometrium, has allowed a
      separate assessment of embryo and endometrial development. Endometrial
      receptivity can be induced by exogenously administered E(2) and P in a variety of
      regimens. The degree of synchrony between embryo and endometrium influences the
      probability of embryo implantation and may be controlled by initiating P
      stimulation at different times relative to the stage of embryo development. Many
      substances have been investigated as adjuncts to E(2) and P in the induction of
      endometrial receptivity, but at the present time, their value is unproven.
      CONCLUSION(S): Estrogen and P are the only hormones necessary to prepare the
      endometrium for implantation.

PMID- 21880275
TI  - Clinical outcomes and development of children born after intracytoplasmic sperm
      injection (ICSI) using extracted testicular sperm or ejaculated extreme severe
      oligo-astheno-teratozoospermia sperm: a comparative study.
AB  - OBJECTIVE: To evaluate the clinical outcomes and development of children born
      after intracytoplasmic sperm injection (ICSI) with extracted testicular sperm or
      ejaculated extreme severe oligo-astheno-teratozoospermia (OAT) sperm. DESIGN:
      Retrospective study. SETTING: Infertility clinic at Chang Gung Memorial Hospital.
      PATIENT(S): A total of 126 ICSI cycles were performed using extracted testicular
      sperm from men with azoospermia and 65 ICSI cycles using fresh ejaculated sperm
      from men with extreme severe OAT. INTERVENTION(S): Retrospective analysis of
      clinical outcomes and development of children born after ICSI with extracted
      testicular sperm or ejaculated extreme severe OAT sperm. MAIN OUTCOME MEASURE(S):
      Fertilization rates, number of grade 1 zygotes and number of embryos produced,
      implantation rate, clinical pregnancy rate, abortion and live birth rate per
      transfer, perinatal outcomes, and birth defects. RESULT(S): The demographic and
      clinical factors, including age, E(2) level on hCG day, number of oocytes
      retrieved, normal fertilization rate, zygote grade 1 score distribution, number
      of top-quality embryos transferred, clinical pregnancy rate per transfer,
      chemical pregnancy rate per transfer, implantation rate, live birth rate per
      transfer, and abortion rate per transfer, were similar between the groups. Sixty
      live births resulted from 48 extracted testicular sperm cycles and 21 live births
      from 19 extreme severe OAT. The obstetric and perinatal outcomes were similar
      between the groups, and children conceived by using ICSI were healthy and without
      major psychomotor or intellectual development retardation. One case of tetralogy
      of Fallot occurred in each group. CONCLUSION(S): There is no evidence of
      differences in the clinical outcomes and development of children result after
      ICSI with extracted testicular sperm or ejaculated extreme severe OAT sperm.

PMID- 21880276
TI  - Antral follicle counts are strongly associated with live-birth rates after
      assisted reproduction, with superior treatment outcome in women with polycystic
      ovaries.
AB  - OBJECTIVE: To evaluate the association of antral follicle count (AFC) with in
      vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) outcome in a
      large unselected cohort of patients covering the entire range of AFC. DESIGN:
      Prospective observational study. SETTING: University-affiliated private
      infertility center. PATIENT(S): 2,092 women undergoing 4,308 IVF-ICSI cycles.
      INTERVENTION(S): AFC analyzed for associations with treatment outcome and
      statistically adjusted for repeated treatments and age. MAIN OUTCOME MEASURE(S):
      Pregnancy rate, live-birth rate, and stimulation outcome parameters. RESULT(S):
      The AFC was log-normally distributed. Pregnancy rates and live-birth rates were
      positively associated with AFC in a log-linear way, leveling out above AFC ~30.
      Treatment outcome was superior among women with polycystic ovaries, independent
      from ovulatory status. The findings were significant also after adjustment for
      age and number of oocytes retrieved. CONCLUSION(S): Pregnancy and live-birth
      rates are log-linearly related to AFC. Polycystic ovaries, most often excluded
      from studies on ovarian reserve, fit as one extreme in the spectrum of AFC; a low
      count constitutes the other extreme, with the lowest ovarian reserve and poor
      treatment outcome. The findings remained statistically significant also after
      adjustment for the number of oocytes retrieved, suggesting this measure of
      ovarian reserve comprises information on oocyte quality and not only quantity.

PMID- 21880277
TI  - Impact of endogenous luteinizing hormone serum levels on progesterone elevation
      on the day of human chorionic gonadotropin administration.
AB  - OBJECTIVE: To assess the relationship between endogenous LH serum levels after
      GnRH analogue administration and serum P elevation on the day of hCG
      administration (P hCG). DESIGN: Retrospective study. SETTING: Reproductive
      medicine center in a university hospital. PATIENT(S): A total of 708 patients
      undergoing a GnRH agonist or antagonist protocol for IVF intracytoplasmic sperm
      injection. INTERVENTION(S): Controlled ovarian stimulation. MAIN OUTCOME
      MEASURE(S): Serum P values according to GnRH analogue; correlation between serum
      LH measurements and P hCG values. RESULT(S): Serum P hCG values were
      significantly lower following the GnRH antagonist than agonist protocol. A
      positive correlation between serum P hCG and LH area under the curve or day 6 LH
      values was found in the GnRH agonist group and between P hCG and LH hCG levels in
      both GnRH analogue regimens. With multivariate analysis, P hCG values were
      positively correlated with serum E(2) levels on hCG administration day and with
      the total FSH dose in both GnRH analogue-treated groups. Additionally, the
      correlation between serum P hCG and LH hCG values was positive in patients
      treated with the GnRH agonist protocol. CONCLUSION(S): The lower serum P levels
      on hCG administration day following the GnRH antagonist protocol are mainly
      explained by lower granulosa cell steroidogenic activity. The correlation with
      serum LH hCG values was positive in the GnRH agonist-treated group.

PMID- 21880278
TI  - A randomized controlled trial of NuvaRing versus combined oral contraceptive
      pills for pretreatment in in vitro fertilization cycles.
AB  - OBJECTIVE: To determine whether use of the NuvaRing (Merck) for pretreatment in
      IVF cycles would result in better cycle control and patient satisfaction versus a
      30-MUg oral contraceptive (OC) pill. DESIGN: A prospective randomized, controlled
      study. SETTING: An academic, hospital-based fertility clinic in Toronto, Canada.
      PATIENT(S): Patients 18-37 years old, undergoing their first IVF or
      IVF/intracytoplasmic sperm injection (ICSI) cycle. INTERVENTION(S): OC versus
      NuvaRing for IVF pre-treatment. MAIN OUTCOME MEASURE(S): Patient satisfaction,
      ovarian suppression, and IVF cycle outcomes. RESULT(S): Demographic data were
      similar in both groups. There were no significant differences in side effects
      between the NuvaRing and OC pill group with the exception of more breast
      discomfort in the OC pill group. There were no differences in the protocols, days
      of stimulation, and number of oocytes between the groups. Patients in the OC pill
      group had more embryos on day 3 and more patients had excess embryos for
      freezing. The number of embryos transferred and clinical pregnancy rates (PR)
      were similar between the two groups, although more patients in the NuvaRing group
      had cycles cancelled for poor stimulation. CONCLUSION(S): There was no
      significant benefit in patient tolerability or side effects with the NuvaRing
      versus the OC pill for IVF pretreatment; however, side effects overall were low
      in both groups. Clinical PRs were similar; however, the NuvaRing group had more
      cancelled cycles and fewer excess embryos for freezing. CLINICAL TRIAL
      REGISTRATION: #NCT01298128.

PMID- 21880280
TI  - Lymphatic spread of endometriosis to pelvic sentinel lymph nodes: a prospective
      clinical study.
AB  - OBJECTIVE: To establish the prevalence of endometriosis metastatic to pelvic
      sentinel lymph nodes (PSLN) in women with ovarian and/or peritoneal
      endometriosis. DESIGN: Prospective clinical study. SETTING: Academic research
      institution. PATIENT(S): Women with a laparoscopic diagnosis of ovarian and/or
      peritoneal endometriosis verified by intraoperative frozen section analysis.
      INTERVENTION(S): Resection of endometriotic lesions and PSLN after cervical blue
      dye injection. MAIN OUTCOME MEASURE(S): Histologic analysis of PSLN for the
      presence of endometriosis and immunohistochemical analysis of estrogen receptor
      (ER), progesterone receptor (PR), cytokeratin (CK), and CD-10 expression.
      RESULT(S): The study enrolled 26 women with suspected endometriosis;
      endometriosis was confirmed in 23 women, and a PSLN was identified in 19 women. A
      total of 37 (right side: 20; left side: 17) lymph nodes were removed. The
      prevalence of endometriotic lesions in PSLN was 11% (2 of 19). Both lesions were
      positive for ER, PR, CK, and CD-10. Isolated endometriotic-like cells (IELCs)
      staining positive for ER and PR were identified in the peripheral sinus of 16
      (80%) of 20 and 14 (70%) of 20 PSLN, respectively. All IELCs lacked CK staining,
      whereas CD-10 staining was present in 16 (80%) of 20 cases, indicating a stromal
      origin of IELCs. Intraoperative and/or postoperative complications were observed
      in 1 (5%) of 19 women. CONCLUSION(S): Spread of IELCs to PSLN is common in
      ovarian and/or peritoneal endometriosis. Metastatic lesions in PSLN are present
      in 11% of women. Further studies to evaluate the prognostic and predictive value
      of endometriotic spread to PSLN are warranted.

PMID- 21880279
TI  - Low-dose mifepristone increases uterine natural killer cell cytotoxicity and
      perforin expression during the receptive phase.
AB  - OBJECTIVE: To investigate the immunologic mechanism by which low-dose
      mifepristone serves as an anti-implantation contraceptive drug. DESIGN: In vitro
      study. SETTING: University hospital and research laboratory. PATIENT(S): Fifteen
      normally cycling patients at the "window of implantation." INTERVENTION(S): A
      human endometrial explant system was used to study the effects of low-dose
      mifepristone (65 and 200 nmol/L) on uterine natural killer (uNK) cells.
      Endometrial samples were treated with different concentrations of mifepristone.
      MAIN OUTCOME MEASURE(S): The cytotoxicity of uNK cells to K562 target cells and
      the expression of perforin (PFN) by uNK cells were examined using a methyl
      thiazolyl tetrazolium (MTT) assay and double immunohistochemistry, respectively.
      RESULT(S): Both uNK cell cytotoxicity and expression of PFN were increased after
      treatment with 65 or 200 nmol/L mifepristone, and these effects were dose
      dependent. CONCLUSION(S): Mifepristone may negatively regulate implantation by
      increasing the cytotoxicity of uNK cells, and this increased cytotoxicity may
      result from increased PFN expression. These findings provide further evidence to
      support the potential contraceptive activity of low-dose mifepristone.

PMID- 21880281
TI  - Prevalence of uterine leiomyomas in lymphangioleiomyomatosis.
AB  - OBJECTIVE: To determine the frequency of uterine leiomyomas and hysterectomy in
      patients with lymphangioleiomyomatosis (LAM), a disease characterized by
      proliferation of abnormal-appearing smooth muscle-like cells. DESIGN:
      Retrospective study. SETTING: Natural history study at the National Institutes of
      Health. PATIENT(S): 456 patients with sporadic LAM and LAM associated with
      tuberous sclerosis complex (LAM/TSC). INTERVENTION(S): Review of records and
      pelvic computed axial tomography scans. MAIN OUTCOME MEASURE(S): Prevalence of
      uterine leiomyomas and hysterectomy. RESULT(S): A total of 174 women had uterine
      leiomyomas (38%). One hundred eighteen were diagnosed by computed tomographic
      scan and 56 were diagnosed by hysterectomy. Among 323 patients who did not have
      hysterectomy, 105 of 270 patients (39%) with sporadic LAM and 13 of 53 (25%) with
      LAM/TSC had uterine leiomyomas. Hysterectomy was performed in 108 of 378 subjects
      with sporadic LAM and 25 of 78 with LAM/TSC. Fifty-six patients were found to
      have uterine fibroids on hysterectomy. The most common indications for
      hysterectomy were uterine leiomyoma, LAM, and endometriosis. CONCLUSION(S):
      Uterine leiomyomas are not more common in LAM than in the general population.
      However, in LAM, the frequency of hysterectomy is higher because of it having
      been recommended for treatment of LAM.

PMID- 21880283
TI  - Retraction. Submucous myomas and their implications in the pregnancy rates of
      patients with otherwise unexplained primary infertility undergoing hysteroscopic
      myomectomy: a randomized matched control study.
AB  - This article has been retracted at the request of the editors of Fertility and
      Sterility as it duplicates parts of a paper that had already appeared in Hum
      Reprod 2005;20:1632-5, doi:10.1093/humrep/deh822.

PMID- 21880282
TI  - Effects of 1,25(OH)2 vitamin D3 on cytokine production by endometrial cells of
      women with recurrent spontaneous abortion.
AB  - OBJECTIVE: To investigate immunomodulatory effect of 1,25(OH)2 vitamin D3
      (1,25(OH)2D3) on cytokine production by endometrial cells of women with
      unexplained recurrent spontaneous abortion (URSA). DESIGN: In vitro study.
      SETTING: Academic research center. PATIENT(S): Patients with URSA and healthy
      controls. INTERVENTION(S): Treatment with 1,25(OH)2D3. MAIN OUTCOME MEASURE(S):
      Production of interferon gamma (IFN-gamma), interleukin-10 (IL-10), transforming
      growth factor beta (TGF-beta), IL-17, IL-6, and IL-8 by whole endometrial cells
      (WECs) and endometrial stromal cells in the presence and absence of 1,25(OH)2D3
      and 1alpha-hydroxylase activity of these cell populations were measured in
      patients with URSA and healthy controls. RESULT(S): 1,25(OH)2D3 interfered with
      production of cytokines by WECs of the control and URSA groups, except IL-8 which
      was increased in URSA group. In endometrial stromal cells, 1,25(OH)2D3 down
      regulated cytokine production as well with stimulatory effect on the production
      of TGF-beta in patients with URSA. Cytokine profile of WECs from patients with
      URSA skewed toward TH2 phenotype after treatment with 1,25(OH)2D3. Endometrial
      cells of both groups had comparable capacity to produce 1,25(OH)2D3.
      CONCLUSION(S): Considering the complex network of immunoregulation at the
      fetomaternal interface, potential beneficial effects of vitamin D3 in patients
      with URSA need to be investigated in clinical practice. Comparable levels of
      1,25(OH)2D3 production and similar trend of cytokine expression by WECs of URSA
      and control groups after vitamin D3 treatment reflect the same local metabolic
      machinery of this hormone.

PMID- 21880284
TI  - Can 15-month-old infants understand pretence? An investigation using the
      'violation-of-expectation' paradigm.
AB  - Productive tests are unsuitable for measuring infants' earliest understanding of
      pretence, because performance demands may render infants unable to produce the
      actions required to pass the test. Recently, Onishi, Baillargeon and Leslie
      (2007) used the violation-of-expectation (VOE) paradigm as a measure of infants'
      understanding of others' pretence that is free from such performance demands.
      They found that 15-month-old infants looked longer at an Unexpected event in
      which an actor pretended to pour into one cup but pretended to drink from another
      cup, compared to pretending to pour and drink with the same cup. On this basis,
      they argued that 15-month-old infants expect others' pretence to be consistent,
      demonstrating their understanding of others' pretence. However, infants may have
      responded to expectations they had about familiar action sequences, rather than
      to pretence per se. To test this hypothesis, the current study firstly replicated
      Onishi et al.'s results in a sample of 28 typically developing 15-month-old
      infants, and then added a condition using closely matched real versions of their
      pretend VOE tasks. It was found that infants looked longer at unexpected events,
      whether or not the events were real or pretend. It was concluded that 15-month
      old infants may look longer at pretend events due to violations of expectations
      they have about familiar action sequences, rather than because they understand
      others' pretence behaviour.

PMID- 21880285
TI  - Dynamic aspects of small bubble and hydrophilic solid encounters.
AB  - The capture of solid particles suspended in aqueous solution by rising gas
      bubbles involves hydrodynamic and physicochemical processes that are central to
      colloid science. Of the collision, attachment and aggregate stability aspects to
      the bubble-particle interaction, the crucial attachment process is least
      understood. This is especially true of hydrophilic solids. We review the current
      literature regarding each component of the bubble-particle attachment process,
      from the free-rise of a small, clean single bubble, to the collision, film
      drainage and interactions which dominate the attachment rate. There is a
      particular focus on recent studies which employ single, very small bubbles as
      analysis probes, enabling the dynamic bubble-hydrophilic particle interaction to
      be investigated, avoiding complications which arise from fluid inertia,
      deformation of the liquid-vapour interface and the possibility of surfactant
      contamination.

PMID- 21880286
TI  - Effect of bariatric surgery on cardiovascular risk profile.
AB  - Obesity is associated with increased risk for cardiovascular (CV) disease (CVD)
      and CV mortality. Bariatric surgery has been shown to resolve or improve CVD risk
      factors, to varying degrees. The objective of this systematic review was to
      determine the impact of bariatric surgery on CV risk factors and mortality. A
      systematic review of the published research was performed to evaluate evidence
      regarding CV outcomes in morbidly obese bariatric patients. Two major databases
      (PubMed and the Cochrane Library) were searched. The review included all original
      reports reporting outcomes after bariatric surgery, published in English, from
      January 1950 to July 2010. In total, 637 studies were identified from the initial
      screen. After applying inclusion and exclusion criteria, 52 studies involving
      16,867 patients were included (mean age 42 years, 78% women). The baseline
      prevalence of hypertension, diabetes, and dyslipidemia was 49%, 28%, and 46%,
      respectively. Mean follow-up was 34 months (range 3 to 155), and the average
      excess weight loss was 52% (range 16% to 87%). Most studies reported significant
      decreases postoperatively in the prevalence of CV risk factors, including
      hypertension, diabetes, and dyslipidemia. Mean systolic pressure reduced from to
      139 to 124 mm Hg and diastolic pressure from 87 to 77 mm Hg. C-reactive protein
      decreased, endothelial function improved, and a 40% relative risk reduction for
      10-year coronary heart disease risk was observed, as determined by the Framingham
      risk score. In conclusion, this review highlights the benefits of bariatric
      surgery in reducing or eliminating risk factors for CVD. It provides further
      evidence to support surgical treatment of obesity to achieve CVD risk reduction.

PMID- 21880287
TI  - Comparison of coronary microcirculation in female nurses after day-time versus
      night-time shifts.
AB  - Nightshift work, which is known to cause mental stress and disrupt normal
      biological diurnal rhythms, leads to endothelial dysfunction resulting in
      increased risk for cardiovascular disease. This study aimed to investigate the
      acute effect of night-shift work on coronary microcirculation through assessment
      of coronary flow reserve (CFR) by transthoracic Doppler echocardiography. This
      study consisted of 36 women nurses who underwent transthoracic Doppler
      echocardiographic examinations after working a nightshift and on a regular day
      without previous nightshift work. Flow velocity in the distal portion of the left
      anterior descending coronary artery was measured at baseline and during adenosine
      infusion. CFR was calculated as the ratio of hyperemic to basal mean diastolic
      flow velocity. CFR after night work was lower than that on a regular workday (3.8
      +/- 0.6 vs 4.1 +/- 0.6, p <0.001). Degree of decreases in CFR after night work
      was correlated to Framingham risk score (r = 0.35, p = 0.036). In conclusion,
      this study demonstrated that coronary microcirculation was impaired after
      nightshift work in women nurses.

PMID- 21880288
TI  - Training present and future cardiologists.
AB  - The future of cardiology rests in the hands and minds of cardiovascular trainees
      and fellowship programs. Education and training is rapidly changing, and the
      paradigm of "see one, do one, teach one" has now been replaced by formal
      assessments of competency, the incorporation of practice improvement and systems
      based practice, and a focus on duty hours. To keep up with the expanding
      knowledge and science in cardiovascular medicine, the cardiology community needs
      to understand new educational initiatives and formulate pathways to teach,
      mentor, and educate trainees to become competent cardiovascular specialists. The
      author highlights some of the present and future issues facing cardiovascular
      training.

PMID- 21880289
TI  - Clinical outcomes of high on-treatment platelet reactivity in Koreans receiving
      elective percutaneous coronary intervention (from results of the CROSS VERIFY
      study).
AB  - Platelet reactivity after clopidogrel therapy varies among patients. Whether
      clopidogrel response variability can predict clinical outcomes has not been
      verified in Asians. A prospective cohort was analyzed to evaluate clinical impact
      of clopidogrel response variability in patients who underwent elective
      percutaneous coronary intervention (PCI). A total of 809 consecutive patients
      receiving clopidogrel after elective PCI were followed for 1 year. On-treatment
      platelet reactivity (OPR) after clopidogrel therapy was measured with a point-of
      care test, the VerifyNow P2Y12 assay. The primary end point was the composite of
      cardiac death and nonfatal myocardial infarction (MI) at 1 year. In this
      exclusively Korean cohort, the median OPR was 236 P2Y12 reactivity units. Using
      the definition of OPR >=235 P2Y12 reactivity units as high OPR (HOPR), 50.3% of
      the cohort showed HOPR. The group with HOPR had significantly higher rates of
      cardiac death and spontaneous MI (2.5% vs 0.5%, p = 0.022) than the group without
      HOPR. Multivariate-adjusted analysis showed that HOPR was an independent
      predictor of the composite of cardiac death and nonfatal MI. The difference in
      major adverse cardiac events between the groups with and without HOPR was more
      profound in those without major cardiovascular disease, such as hypertension,
      diabetes mellitus, or dyslipidemia. In conclusion, HOPR to clopidogrel was
      significantly associated with cardiac death and spontaneous MI after elective
      PCI, suggesting that clopidogrel response variability may be a significant risk
      factor of hard end points in Koreans.

PMID- 21880290
TI  - Predictors and course of high-degree atrioventricular block after transcatheter
      aortic valve implantation using the CoreValve Revalving System.
AB  - Transcatheter aortic valve implantation (TAVI) is a novel treatment for high risk
      or inoperable patients with symptomatic severe aortic stenosis. However,
      significant atrioventricular (AV) conduction system abnormalities requiring
      permanent pacemaker (PPM) implantation might complicate this procedure. We used
      best subsets logistic regression analysis to identify the independent predictors
      for the development of high-degree AV block (HDAVB) among 70 patients who
      underwent TAVI at 3 referral centers in Israel from 2008 to 2010. The mean age of
      the study patients was 83 +/- 4.6 years. Of the 70 patients, 28 (40%) developed
      AV conduction abnormalities requiring PPM implantation within 14 days (median 2)
      of the procedure. The indications for PPM implantation were HDAVB (n = 25), new
      onset left bundle branch block with PR prolongation (n = 2), and slow atrial
      fibrillation (n = 1). Best subsets logistic regression analysis showed that,
      among the 15 prespecified clinical, electrocardiographic, and echocardiographic
      candidate risk factors, only right bundle branch block at baseline (odds ratio
      43; p = 0.002) and deep valve implantation (<6 mm from the lower edge of the
      noncoronary cusp to the ventricular end of the prosthesis, odds ratio 22; p
      <0.001) were independently associated with the development of periprocedural
      HDAVB. At 3 months of follow-up, HDAVB was still present in 40% of the patients
      who received PPM implantation for this indication. In conclusion, 40% of the
      patients who undergo CoreValve TAVI require PPM implantation after the procedure,
      with most cases (36%) associated with the development of postprocedural HDAVB.
      Baseline conduction abnormalities (right bundle branch block) and deep valve
      implantation (>6 mm) independently predicted the development of HDAVB and the
      need for PPM implantation after CoreValve TAVI.

PMID- 21880291
TI  - Threshold for the upper normal limit of indexed epicardial fat volume: derivation
      in a healthy population and validation in an outcome-based study.
AB  - Epicardial fat volume (EFV) quantified on noncontrast cardiac computed tomography
      relates to cardiovascular prognosis. We sought to define the upper normal limit
      of body surface area (BSA)-indexed EFV (EFVi) in a healthy population and to
      validate it as a predictor of major adverse cardiovascular events (MACE). We
      analyzed noncontrast cardiac computed tomography scans of 226 healthy subjects
      with a low Framingham Risk Score (FRS; <=6%) performed for coronary calcium
      scoring (CCS). EFV was quantified using validated software and indexed to BSA. We
      defined the 95th percentile as the upper normal limit. Subsequently, we
      reanalyzed a separate cohort of 232 participants from a previously published case
      control study with 4-year follow-up and 58 cases of MACE to test the additive
      value of an abnormally high EFVi for predicting MACE. Of the 226 healthy
      participants 51% were men (mean age 52 +/- 9 years). EFV correlated to BSA (r =
      0.373, p <0.0001). Median, range, and 25th and 75th percentiles of the non
      normally distributed EFVi were 33.3, 10.8 to 96.6, and 24.5 and 45.5 cm(3)/m(2).
      The 95th percentile definition of the upper normal limit of EFVi was 68.1
      cm(3)/m(2). For prediction of MACE, EFVi values higher than the newly defined
      threshold emerged as a significant and independent predictor after controlling
      for confounders (odds ratio 2.8, 95% confidence interval 1.3 to 6.4, p = 0.012)
      and trended in its additive value to the combination of CCS >=400 and FRS (area
      under the receiver operating characteristic curve 0.714 vs 0.675, p = 0.1277). In
      conclusion, in a healthy population we determined 68.1 cm(3)/m(2) as the 95th
      percentile threshold for abnormally high EFVi. EFVi exceeding this value
      independently predicted MACE and trended to add to CCS and FRS in this
      prediction.

PMID- 21880292
TI  - Comparison of characteristics, management practices, and outcomes of patients
      between the global registry and the gulf registry of acute coronary events.
AB  - The Arab Middle East is a unique region of the developing world where little is
      known about the outcomes of patients hospitalized with an acute coronary syndrome
      (ACS), despite playing an important role in the global burden of cardiovascular
      disease. The primary objectives of this observational study were to compare
      patients with ACS hospitalized in the Arab Middle East to patients enrolled in a
      multinational non-Arabian ACS registry. The study cohort consisted of patients
      hospitalized in 2007 with an ACS including 4,445 from the Global Registry of
      Acute Coronary Events (GRACE) and 6,706 from the Gulf Registry of Acute Coronary
      Events (Gulf RACE). Average age of patients in Gulf RACE was nearly a decade
      younger than that in GRACE (56 vs 66 years). Patients in Gulf RACE were more
      likely to be men, diabetic, and smoke and less likely to be hypertensive compared
      to patients in GRACE. Patients in Gulf RACE had higher odds of receiving aspirin
      and a lower likelihood of receiving angiotensin-converting enzyme
      inhibitors/angiotensin receptor blockers, beta blockers, and clopidogrel during
      their index hospitalization. Although most eligible patients with ST-elevation
      myocardial infarction in Gulf RACE received thrombolytics, most of their
      counterparts in GRACE underwent a primary percutaneous coronary intervention.
      Multivariable adjusted in-hospital case-fatality rates were not significantly
      different between patients in Gulf RACE and those in GRACE. In conclusion,
      despite differences in patient characteristics and treatment practices, short
      term mortality rates were comparable in patients with ACS enrolled in these 2
      registries. Future studies should explore the effects of these differences on
      long-term prognosis and other pertinent patient outcomes.

PMID- 21880294
TI  - Electrohysterographic propagation velocity for preterm delivery prediction.

PMID- 21880293
TI  - Relation of left ventricular ejection fraction to cognitive aging (from the
      Framingham Heart Study).
AB  - Heart failure is a risk factor for Alzheimer's disease and cerebrovascular
      disease. In the absence of heart failure, it was hypothesized that left
      ventricular ejection fraction (LVEF), an indicator of cardiac dysfunction, would
      be associated with preclinical brain magnetic resonance imaging (MRI) and
      neuropsychological markers of ischemia and Alzheimer disease in the community.
      Brain MRI, cardiac MRI, neuropsychological, and laboratory data were collected
      from 1,114 Framingham Heart Study Offspring Cohort participants free from
      clinical stroke or dementia (aged 40 to 89 years, mean age 67 +/- 9 years, 54%
      women). Neuropsychological and neuroimaging markers of brain aging were related
      to cardiac MRI-assessed LVEF. In multivariable-adjusted linear regressions, LVEF
      was not associated with any brain aging variable (p values >0.15). However, LVEF
      quintile analyses yielded several U-shaped associations. Compared to the referent
      (quintile 2 to 4), the lowest quintile (quintile 1) LVEF was associated with
      lower mean cognitive performance, including Visual Reproduction Delayed Recall
      (beta = -0.27, p <0.001) and Hooper Visual Organization Test (beta = -0.27, p
      <0.001). Compared to the referent, the highest quintile (quintile 5) LVEF values
      also were associated with lower mean cognitive performance, including Logical
      Memory Delayed Recall (beta = -0.18, p = 0.03), Visual Reproduction Delayed
      Recall (beta = -0.17, p = 0.03), Trail Making Test Part B - Part A (beta = -0.22,
      p = 0.02), and Hooper Visual Organization Test (beta = -0.20, p = 0.02). Findings
      were similar when analyses were repeated excluding prevalent cardiovascular
      disease. In conclusion, although these observational cross-sectional data cannot
      establish causality, they suggest a nonlinear association between LVEF and
      measures of accelerated cognitive aging.

PMID- 21880295
TI  - Significant correlation between visual acuity and recovery of foveal cone
      microstructures after macular hole surgery.
AB  - PURPOSE: To determine whether a recovery of the microstructures of the foveal
      photoreceptors after macular hole closure is correlated with best-corrected
      visual acuity (BCVA). DESIGN: Retrospective, consecutive, observational case
      series. METHODS:  SETTING: Single-center academic practice. STUDY POPULATION:
      Forty-one eyes of 41 patients with surgically closed macular holes. OBSERVATIONAL
      PROCEDURES: The presence and intactness of the cone outer segment tips (COST)
      line were determined by spectral-domain optical coherence tomography and compared
      with the presence of the inner segment/outer segment (IS/OS) junction and the
      external limiting membrane (ELM) at 1, 3, 6, 9, and 12 months after the macular
      hole surgery. MAIN OUTCOME MEASURE: The correlation between the integrity of the
      foveal photoreceptor microstructures and the BCVA. RESULTS: A distinct COST line
      was first seen at 6 months after the surgery. A distinct or irregular COST line
      was observed only in eyes with an intact IS/OS junction and ELM. Eyes with a
      distinct or irregular COST line had significantly better BCVA than those with a
      disrupted COST line in eyes with an intact IS/OS junction and ELM at 12 months (P
      = .030). The BCVA was >=20/25 at 12 months in 91% of the eyes with a distinct or
      irregular COST line but in only 44% of the eyes without a COST line (P = .015).
      CONCLUSIONS: The significant correlation between the BCVA and a distinct or
      irregular COST line after successful macular hole surgery indicates that the
      recovery of foveal cone microstructure is associated with good postoperative
      BCVA.

PMID- 21880296
TI  - Response to: Do pregnant women have improved outcomes after traumatic brain
      injury?

PMID- 21880297
TI  - Unnecessary perioperative antibiotic prophylaxis in the placement of totally
      implanted central venous access ports should be avoided.

PMID- 21880298
TI  - Transcatheter aortic valve implantation or surgical aortic valve replacement as
      redo procedure after prior coronary artery bypass grafting.
AB  - BACKGROUND: The perioperative risk for redo surgical aortic valve replacement (S
      AVR) in patients with severe aortic stenosis and prior coronary artery bypass
      grafting (CABG) is increased. Transcatheter aortic valve implantation (TAVI)
      represents an alternative. We assessed the perioperative and mid-term clinical
      outcome of patients undergoing S-AVR or TAVI. METHODS: In a retrospective
      observational, comparative study, 40 consecutive patients underwent redo
      operation with S-AVR or TAVI between April 2005 and April 2010. Median sternotomy
      and extracorporeal circulation were used for S-AVR; TAVI access was transfemoral
      (n = 27; 67.5%), transapical (n = 11; 27.5%), or transsubclavian (n = 2; 5.0%).
      Clinical and echocardiographic follow-up was at 30 days and 6 months. RESULTS:
      TAVI patients were older (78.5 +/- 6 vs 70.6 +/- 8 years, p < 0.001) and
      presented higher logistic (33.5 +/- 17 vs 20.2 +/- 14, p < 0.001) European System
      for Cardiac Operative Risk Evaluation scores. All-cause mortality was 2.5% in
      both groups and major adverse cardiac and cerebrovascular event rates were
      comparable (7.5% TAVI vs 17.5% S-AVR, p = 0.311) after 30 days. TAVI was
      associated with a higher rate of permanent pacemaker implantation (30% vs 0%, p <
      0.001) and grade II residual aortic regurgitation in 14%. Incidence of
      cerebrovascular events was 7.5% in S-AVR vs 2.5% in TAVI (p = 0.61). CONCLUSIONS:
      In elderly, high-risk patients after prior CABG, conventional aortic valve
      replacement and TAVI are comparable treatment options with favorable clinical
      outcome. A redo operation itself does not sufficiently justify a TAVI approach.

PMID- 21880299
TI  - A medical hand tool physical interaction evaluation approach for prototype
      testing using patient care simulators.
AB  - The purpose of this study was to develop and test a physical ergonomics
      assessment approach for medical device handles. The method assesses wrist posture
      and force of exertion simultaneously by task element. Electrogoniometers and EMG
      sensors were connected through a data acquisition module for synchronization with
      video recordings of trials. Task analysis of video recordings were performed
      offline with Observer XT software. Average posture and force data across several
      repetitions of individual task elements were calculated and presented in a format
      suitable for informing product designers of specific issues during a test trial.
      A handle comfort questionnaire is proposed to survey subjective responses. The
      evaluation approach was applied to an endoscope needle in sampling a biopsy from
      the stomach wall using a gastrointestinal track simulator with ten physician
      surrogates. The results showed that for all task elements the wrist was in
      extension (33( degrees )-45( degrees )). Peak muscle forces ranged from 28% to
      68% MVC across the three muscles studied. Muscle peak forces were above ACGIH HAL
      maximum threshold limits for four of the seven task elements, and above the
      action limit for all seven task elements for two muscles. The handle comfort
      questionnaire data also supported the high muscle force findings, and also on
      force distribution on the handle due to contact stresses. This combined approach
      could be used to collect and report detailed early stage ergonomics data from
      user trials on patient care simulators. The approach is proposed for use by
      medical device designers at the design stage of new products using prototypes,
      but it could also be used on existing products with real patients.

PMID- 21880300
TI  - Retention of motor changes in chronic stroke survivors who were administered
      mental practice.
AB  - OBJECTIVE: To determine retention of motor changes 3 months after participation
      in a regimen consisting of mental practice (MP) combined with repetitive task
      specific (RTP) practice. DESIGN: Prospective, blinded, cohort, pre-post study.
      SETTING: Outpatient rehabilitation hospital. PARTICIPANTS: Individuals (N=21) in
      the chronic stage of stroke (mean age +/- SD, 66.1 +/- 8.1y; age range, 56-76y;
      mean time since stroke at study enrollment, 58.7mo; range, 13-129mo) exhibiting
      mild to moderate impairments of hand function. INTERVENTIONS: All individuals had
      been randomly assigned to receive a 10-week regimen consisting of MP emphasizing
      paretic upper extremity (UE) use during valued activities. Directly after each of
      these sessions, subjects were administered audiotaped MP. We assessed this
      group's paretic UE motor levels before, after, and 3 months after intervention.
      MAIN OUTCOME MEASURES: The UE section of the Fugl-Meyer Assessment of
      Sensorimotor Impairment (FM), the Action Research Arm Test (ARAT), the Arm Motor
      Ability Test (AMAT), and the Box and Block Test (BB). RESULTS: None of the scores
      significantly changed from the period directly after intervention to the 3-month
      posttesting period (FM: t=.817; ARAT: t=.923; AMAT: t=.898, t=.818, and t=.967
      for the Functional Ability, Quality of Movement, and Time scales, respectively;
      BB: t=.892). CONCLUSIONS: Changes in paretic UE movement realized through MP
      combined with RTP (MP + RTP) participation are retained 3 months after the
      intervention has concluded. This is the first study examining retention of motor
      changes after MP + RTP participation, and one of only a few studies examining
      long retention of motor changes after any intervention targeting stroke-induced
      hemiparesis.

PMID- 21880301
TI  - Nerve injury-induced changes in GABA(A) and GABA(B) sub-unit expression in area
      3b and cuneate nucleus of adult squirrel monkeys: further evidence of
      developmental recapitulation.
AB  - The primate somatosensory system provides an excellent model system with which to
      investigate adult neural plasticity. Here, we report immunohistochemical staining
      data for the GABA(A) alpha1, GABA(B)R1a, and GABA(B)R1b receptor subunits in
      somatosensory area 3b, and cuneate nucleus one week after median nerve
      compression in adult squirrel monkeys. We find a significant decrease in GABA(A)
      alpha1 subunit staining across all cortical layers and within both soma and
      neuropil of the deprived cortical and brainstem regions. The GABA(B) staining
      showed an opposing shift in deprived regions, with a significant increase in
      presynaptic GABA(B)R1a staining, and a significant decrease in postsynaptic
      GABA(B)R1b staining in deprived regions of the cortex and brainstem. These
      changes in receptor subunit expression generate patterns that are very similar to
      those reported in the neonate. Furthermore, the similarities between brainstem
      and cortical expression suggest conserved forms of adult plasticity in these two
      regions. Taken together these results, along with the results from our previous
      paper investigating AMPA subunit expression in these same animals, support the
      hypothesis that deprived neurons enter a previously hidden state of developmental
      recapitulation that serves to prime the brain for NMDA receptor mediated
      receptive field reorganization.

PMID- 21880303
TI  - Understanding of spoken language under challenging listening conditions in
      younger and older listeners: a combined behavioral and electrophysiological
      study.
AB  - Numerous studies suggested an age-related decline in speech perception under
      difficult listening conditions. Here, spoken language understanding of two age
      groups of listeners was investigated in a naturalistic "stock price monitoring"
      task. Stock prices of listed companies were simultaneously recited by three
      speakers at different positions in space and presented via headphones to 14
      younger and 14 older listeners (age ranges 19-25 and 54-64 years, respectively).
      The listeners had to respond when prices of target companies exceeded a specific
      value, but to ignore all other prices as well as beep sounds randomly
      interspersed within the stock prices. Older listeners did not produce more
      missing responses, or longer response times than younger listeners. However,
      differences in event-related potentials indicated a reduced parietal P3b of
      older, relative to younger, listeners. Separate analyses for those listeners who
      performed relatively high or low in the behavioral task revealed a right-frontal
      P3a that was pronounced especially in the group of high-performing older
      listeners. Correlational analyses indicated a direct relationship between P3a
      amplitude and spoken language comprehension in older, but not younger, listeners.
      Furthermore, younger (especially, low-performing) listeners showed a more
      pronounced P2 on irrelevant beep sounds than older listeners. These subtle
      differences in cortical processing between age groups suggest that high
      performance of older middle-aged listeners in demanding listening situations is
      associated with increased engagement of frontal brain areas, and thus the
      allocation of mental resources for compensation of potential declines in spoken
      language understanding.

PMID- 21880302
TI  - Environmentally induced antinociception and hyperalgesia in rats and mice.
AB  - Stress can enhance and inhibit nociception depending on the situation. Thus,
      simply shifting the context from the elevated plus maze (EPM) which has been
      shown to produce stress-induced antinociception to a different environment could
      produce drastic and rapid changes in nociception. The present experiment tested
      this hypothesis by assessing nociception in rats and mice during and immediately
      after removal from the maze. Experiment 1 found hyperalgesia in female and male
      rats tested on the hot plate immediately after exposure to the elevated plus
      maze. This hyperalgesia occurred with or without the added stress of a hind paw
      formalin injection and regardless of whether rats were exposed to an EPM with
      open (oEPM) or enclosed (eEPM) arms despite a clear antinociceptive effect while
      on the oEPM. Experiment 2 showed a similar shift from antinociception to
      nociception on the formalin test in mice immediately after removing them from the
      EPM. These data demonstrate that a mild stressor such as the EPM can produce both
      antinociception and hyperalgesia depending on the context. This shift from
      antinociception to hyperalgesia occurs rapidly and is evident in mice, male and
      female rats, and with the hot plate and formalin tests.

PMID- 21880304
TI  - Regulation of cerebral blood flow in the hippocampus by neuronal activation
      through the perforant path: relationship between hippocampal blood flow and
      neuronal plasticity.
AB  - Although changes in regional cerebral blood flow (rCBF) have been used as an
      index of neuronal activity, the effects of long-term potentiation (LTP) in the
      hippocampus, widely assumed to be an electrophysiological basis of learning and
      memory, on the changes in rCBF by neuronal activity remain unclear. Hence, to
      elucidate whether the effects of LTP in the hippocampus reflect in the
      correlation between neuronal activity and co-occurring changes in rCBF, we
      investigated the effects of LTP on the responses of hippocampal blood flow (HBF)
      to the electrical stimulation of the perforant path in vivo. We continuously
      measured HBF using Laser-Doppler flowmetry, and systemic blood pressure and heart
      rate were measured from the femoral artery during electrical stimulations in
      halothane-anesthetized rats. The results showed that the reactivity of HBF to
      neuronal activation was potentiated by a tetanic stimulation that induces LTP,
      although the tetanic stimulation did not affect baseline of HBF values. These
      results suggest that the presence of the plasticity between neuronal activity and
      the rCBF in the perforant path-dentate pathway, and the neuronal plasticity can
      be reflected in the transient changes in rCBF when the brain region is activated
      but not in the steady state.

PMID- 21880306
TI  - A comparative study of antioxidative activities of cell-wall polysaccharides.
AB  - Oxidative burst in plants is elicited by biotic and abiotic stressors.
      Analogously to some monosaccharides which act as intracellular antioxidants, cell
      wall polysaccharides may be in charge of buffering free-radical production in the
      extracellular compartment under pronounced prooxidative settings. Although a wide
      range of plant polysaccharides have been examined for their antioxidative
      properties, this usually has not been done in a coherent and comparative manner
      and against biologically relevant reactive species. Here we show that different
      cell-wall polysaccharides, cellulose, pectin, D-galacto-D-mannan,
      arabinogalactan, and xylan, exhibit distinctive antioxidative activities against
      the hydroxyl radical (.OH)-generating Fenton reaction and superoxide. We found,
      using an EPR spin-trapping method, that the main carriers of 'anti-Fenton'
      activity in the plant cell wall are pectin and xylan. They most likely act by
      binding metal ions in such a manner to allow the Fenton reaction, after which
      they scavenge .OH. Such a mode of action is preferred by cells resulting in a
      safe degradation of H(2)O(2). On the other hand, the polysaccharides examined
      showed similar superoxide scavenging capacities. We propose that plants may
      employ different antioxidative characteristics of polysaccharides to regulate
      their redox status by modifying the composition of the cell wall.

PMID- 21880305
TI  - The brain-derived neurotrophic factor is associated with alcohol dependence
      related depression and antidepressant response.
AB  - Brain-derived neurotrophic factor (BDNF) plays an essential role in neuronal
      survival, proliferation, and synaptic remodeling and modulates the function of
      many other neurotransmitters. Additionally, it likely underlies neurodegenerative
      and psychiatric disorders, including alcohol dependence-related depression (AD
      D). Here, we investigated the possible association between three single
      nucleotide polymorphisms (SNPs) of the BDNF gene (rs13306221, rs6265, rs16917204)
      and AD-D. Of 548 patients with alcohol dependence (AD), 166 had AD-D and 312
      healthy controls. Response to 8-week sertraline treatment was also assessed. The
      frequency of the A allele of rs6265 (Val66Met) was significantly higher in AD-D
      patients than in the healthy controls (p=0.009 after Bonferroni correction). The
      analysis revealed a strong association between the rs6265 genotype distribution
      and AD-D (p=0.005 after Bonferroni correction), and the A allele of rs6265 was
      significantly overrepresented in AD-D patients compared to AD without depression
      (AD-nD) patients (p=0.001 after Bonferroni correction). Additionally, carriers of
      the A allele of rs6265 responded better to sertraline treatment (p=0.001). Our
      results suggested a novel association between BDNF rs6265 and AD-D. These
      findings might lead to earlier detection of AD-D, perhaps providing better tools
      for clinical care of these patients in the future.

PMID- 21880307
TI  - [Delayed right hepatic artery haemorrhage after iatrogenic gallbladder by
      laparoscopic cholecystectomy that required a liver transplant due to acute liver
      failure: clinical case and review of the literature].
AB  - INTRODUCTION: Right hepatic artery (RHA) injury after laparoscopic
      cholecystectomy (LC) may go unnoticed clinically, but can sometimes cause
      necrosis of the right lobe. Exceptionally, when the necrosis spreads to segment
      IV, fulminant liver failure (FLF) may occur, and an urgent liver transplantation
      (LT) may be required. PATIENTS AND METHOD: We provide a review of the literature
      on patients with indication for an LT due to vascular damage caused by bile duct
      injury following LC. The case reported herein is the fourth described in the
      specialized literature of LT due to RHA injury after LC and the second of FLF
      after RHA injury. RESULTS: LT due to RHA injury was performed in 3 of 13 patients
      reported in the literature: one LT was performed at 3 months due to FLF, after an
      extended right hepatectomy was performed, and the remaining two were performed
      due to secondary biliary cirrhosis. Our patient was transplanted due to FLF 15
      days after the injury. CONCLUSIONS: RHA injury after LC may require LT due to
      FLF. Although exceptional, this possibility should be considered when there are
      RHA complications that may require occlusion.

PMID- 21880308
TI  - [Safety of a multiperforated catheter implanted in the surgical wound for the
      continuous infusion of local anaesthetics in post-operative analgesia].
AB  - OBJECTIVE: To evaluate the incidence of infection at the surgical site in
      patients who have a multiperforated catheter implant for continuous infusion of a
      local anaesthetic as a local analgesic. PATIENTS AND METHOD: An observational,
      descriptive and prospective study, of one month duration. It included 50 patients
      subjected to selective laparotomy in whom a multiperforated pre-peritoneal
      catheter was implanted for analgesia purposes (Painfusor(r). Baxter). Patients
      with a surgical incision of less than 15 cm and/or ASA>III, were excluded from
      the study. RESULTS: The catheter was removed from all patients at 48 hours. An
      infection at the surgical site was present in 6% of the patients who had the
      catheter implanted, which was similar to the incidence in clean-contaminated
      surgery (5.5%; 95% CI: 3.4-8.7%). Colonisation of the catheter was observed in
      two patients, causing only one infection of the surgical site. CONCLUSIONS: The
      use of an in-situ pre-peritoneal catheter for post-surgical anaesthesia does not
      increase the risk of surgical site infection.

PMID- 21880309
TI  - Cellular oncomiR orthologue in EBV oncogenesis.
AB  - MicroRNAs are small non-coding RNAs that regulate gene expression at multiple
      levels. The discovery of virally encoded miRNAs attracted immense attention
      towards their role in viral replication and pathogenesis. Kaposi's-sarcoma
      associated herpes virus encodes miRNA that functions as an orthologue of human
      cellular miRNA, i.e., hsa-miR-155. Keeping the same view we extended the miRNA
      homology search between the miRNAs of humans and Epstein-Barr virus. The In
      silico analyses shows that EBV encoded miR-BART-5 has a significant 'seed'
      sequence homology to hsa-miR-18 of humans. Further, the mRNA transcripts of the
      human genes involved in cellular growth could potentially be targeted by both
      viral as well as human miRNAs. The known etiological role of hsa-miR-18 as an
      oncomiR suggests that miR-BART-5 may function as viral oncomiR as observed in EBV
      positive gastric carcinoma patients.

PMID- 21880310
TI  - Improving protein secondary structure prediction using a multi-modal BP method.
AB  - Methods for predicting protein secondary structures provide information that is
      useful both in ab initio structure prediction and as additional restraints for
      fold recognition algorithms. Secondary structure predictions may also be used to
      guide the design of site directed mutagenesis studies, and to locate potential
      functionally important residues. In this article, we propose a multi-modal back
      propagation neural network (MMBP) method for predicting protein secondary
      structures. Using a Knowledge Discovery Theory based on Inner Cognitive Mechanism
      (KDTICM) method, we have constructed a compound pyramid model (CPM), which is
      composed of three layers of intelligent interface that integrate multi-modal back
      propagation neural network (MMBP), mixed-modal SVM (MMS), modified Knowledge
      Discovery in Databases (KDD(*)) process and so on. The CPM method is both an
      integrated web server and a standalone application that exploits recent
      advancements in knowledge discovery and machine learning to perform very accurate
      protein secondary structure predictions. Using a non-redundant test dataset of
      256 proteins from RCASP256, the CPM method achieves an average Q(3) score of
      86.13% (SOV99=84.66%). Extensive testing indicates that this is significantly
      better than any other method currently available. Assessments using RS126 and
      CB513 datasets indicate that the CPM method can achieve average Q(3) score
      approaching 83.99% (SOV99=80.25%) and 85.58% (SOV99=81.15%). By using both
      sequence and structure databases and by exploiting the latest techniques in
      machine learning it is possible to routinely predict protein secondary structure
      with an accuracy well above 80%. A program and web server, called CPM, which
      performs these secondary structure predictions, is accessible at
      http://kdd.ustb.edu.cn/protein_Web/.

PMID- 21880311
TI  - Differences in prevalence of sexual dysfunction between primary and secondary
      infertile women.
AB  - OBJECTIVE: To examine the impact of type of infertility on female sexual
      function. DESIGN: Comparison of female sexual function index and prevalence in
      primary infertile women and secondary infertile women. SETTING: Hospital.
      PATIENT(S): One hundred twenty-two primary infertile and 51 secondary infertile
      women. INTERVENTION(S): Questionnaires (Female Sexual Function Index [FSFI] and
      Beck Depression Inventory). MAIN OUTCOME MEASURE(S): Prevalence of dysfunction in
      primary and secondary infertile women. RESULT(S): The prevalence of female sexual
      dysfunction was 64.8% (n = 79) and 76.5% (n = 39) in primary infertile and
      secondary infertile women, respectively. In analyses of mean overall and subgroup
      scores of FSFI, there were significant differences between primary and secondary
      infertile women in the mean scores of orgasm, satisfaction, and total FSFI.
      Backward logistic regression identified a model with four significant predictors
      of sexual dysfunction (group, age, income level, and educational level).
      Secondary infertile women had a 9.5-fold higher risk of sexual dysfunction than
      primary infertile women after adjustment for confounding factors. CONCLUSION(S):
      There was a higher prevalence of sexual dysfunction in secondary infertile women.
      Secondary infertile women have decreased sexual desire, orgasm, and satisfaction
      compared with primary infertile women.

PMID- 21880312
TI  - Obstetric acute renal failure in an intensive care unit in Morocco.

PMID- 21880313
TI  - Developing a model of competence in the operating theatre: psychometric
      validation of the perceived perioperative competence scale-revised.
AB  - AIM: This paper describes the development and validation of the Revised
      Perioperative Competence Scale (PPCS-R). BACKGROUND: There is a lack of a
      psychometrically tested sound self-assessment tools to measure nurses' perceived
      competence in the operating room. METHODS: Content validity was established by a
      panel of international experts and the original 98-item scale was pilot tested
      with 345 nurses in Queensland, Australia. Following the removal of several items,
      a national sample that included all 3209 nurses who were members of the
      Australian College of Operating Room Nurses was surveyed using the 94-item
      version. Psychometric testing assessed content validity using exploratory factor
      analysis, internal consistency using Cronbach's alpha, and construct validity
      using the "known groups" technique. During item reduction, several preliminary
      factor analyses were performed on two random halves of the sample (n=550).
      RESULTS: Usable data for psychometric assessment were obtained from 1122 nurses.
      The original 94-item scale was reduced to 40 items. The final factor analysis
      using the entire sample resulted in a 40 item six-factor solution. Cronbach's
      alpha for the 40-item scale was .96. Construct validation demonstrated
      significant differences (p<.0001) in perceived competence scores relative to
      years of operating room experience and receipt of specialty education.
      CONCLUSIONS: On the basis of these results, the psychometric properties of the
      PPCS-R were considered encouraging. Further testing of the tool in different
      samples of operating room nurses is necessary to enable cross-cultural
      comparisons.

PMID- 21880314
TI  - Rust in the pipes: the importance of oxidative stress in the pathophysiology of
      coronary artery disease and the valuable contribution of translational research.

PMID- 21880315
TI  - Myeloperoxidase, but not oxidized LDL, is associated with leisure-time physical
      activity: results from the MONICA/KORA Augsburg Studies 1984-1995.
AB  - OBJECTIVE: Oxidative stress-induced cell damage contributes to several chronic
      conditions such as cardiovascular disease, but only very few population-based
      studies have examined the influence of regular physical activity (PA) on
      oxidative stress. METHODS: 1820 men and women aged 35-74 years were randomly
      drawn from three population-based MONICA/KORA Augsburg Studies conducted between
      1984 and 1995. Geometric means of the oxidative stress markers myeloperoxidase
      (MPO) and oxidized LDL (ox-LDL) were calculated and multiple linear regression
      was performed to assess their associations with three self-reported PA domains,
      namely work, leisure-time or walking. RESULTS: Mean MPO concentrations were lower
      for participants engaged in high leisure-time PA (124.2 MUg/ml; 95%-CI, 116.8
      132.0) compared to the inactive reference group (133.5 MUg/ml; 95%-CI, 127.6
      139.6) (P(trend) across PA levels: 0.007). No significant association between ox
      LDL and PA domains was observed (P(trend) between 0.162 and 0.803). CONCLUSION:
      These data indicate that regular leisure-time PA may reduce MPO concentrations.

PMID- 21880316
TI  - Increased asymmetric dimethylarginine and enhanced inflammation are associated
      with impaired vascular reactivity in women with endometriosis.
AB  - OBJECTIVE: Enhanced inflammatory responses which may inhibit vascular reactivity,
      are associated with endometriosis development. Asymmetric dimethylarginine
      (ADMA), an inhibitor of endogenous nitric oxide synthase, is also implicated in
      endothelial dysfunction. We aimed to determine whether plasma ADMA and systemic
      inflammation are associated with endothelial function in women with
      endometriosis. METHODS: We evaluated 41 women with and 28 women without
      endometriosis. Plasma levels of lipids and inflammatory markers such as high
      sensitive-C reactive protein (hs-CRP), serum amyloid protein A (SAA), and
      interleukin-6 (IL-6) were measured in the two groups. We also measured levels of
      ADMA and symmetric dimethylarginine (SDMA). High-resolution ultrasonography
      measured flow-mediated vasodilation (FMD) to assess vasodilatory responses.
      RESULTS: FMD was significantly lower in women with endometriosis compared to
      those without endometriosis (8.39 +/- 0.43% vs 10.79 +/- 0.54%, P = 0.001). While
      plasma lipid levels did not differ significantly between groups, levels of AMDA,
      but not SDMA, were significantly higher in women with endometriosis (409.7 +/-
      10.1 pmol/L vs 383.0 +/- 48.3 pmol/L, P = 0.04). Inflammatory markers were also
      significantly higher in these women (hs-CRP: 1053.3 +/- 252.0 ng/mL vs 272.0 +/-
      83.3 ng/mL, P = 0.02; SAA: 8.00 +/- 1.53 MUg/mL vs 3.82 +/- 0.42 MUg/mL, P =
      0.04; IL-6: 2.73 +/- 0.75 pg/mL vs 1.05 +/- 0.60 pg/mL, P = 0.04). FMD was
      negatively correlated with plasma levels of ADMA (r = -0.37, P=0.01) and log hs
      CRP (r = -0.34, P = 0.01). CONCLUSION: Increased plasma ADMA levels and enhanced
      inflammation are associated with inhibited endothelial function in women with
      endometriosis.

PMID- 21880319
TI  - Vortex-assisted surfactant-enhanced-emulsification liquid-liquid microextraction.
AB  - A novel sample pre-treatment technique, based on vortex-assisted surfactant
      enhanced-emulsification liquid-liquid microextraction (VSLLME), followed by gas
      chromatography-flame photometric detection (GC-FPD) has been developed for the
      determination of seven organophosphorus pesticides (OPPs) in wine and honey
      samples. In the VSLLME method, the extraction solvent was dispersed into the
      aqueous samples by the assistance of vortex agitator. Meanwhile, the addition of
      a surfactant, which was used as an emulsifier, could enhance the speed of the
      mass-transfer from aqueous samples to the extraction solvent. The main parameters
      relevant to this method were investigated and the optimum conditions were
      established: 15 MUL chlorobenzene was used as extraction solvent, 0.2 mmol L(-1)
      Triton X-114 was selected as the surfactant, the extraction time was fixed at
      30s, 3% sodium chloride was added and the extraction process was performed under
      the room temperature. Under the optimum conditions, limits of detections (LODs)
      were varied between 0.01 and 0.05 MUg L(-1). The relative standard deviation
      (RSD, n=6) ranged from 2.3% and 8.9%. The linearity was obtained by five points
      in the concentration range of 0.1-50.0 MUg L(-1). Correlation coefficients (r)
      varied from 0.9969 to 0.9991. The enrichment factors (EFs) were in a range of 282
      309. Finally, the proposed method has been successfully applied to the
      determination of target analytes in real samples. The recoveries of the target
      analytes in wine and honey samples were between 81.2% and 108.0%.

PMID- 21880317
TI  - Age-related differences in the morphology of microdamage propagation in
      trabecular bone.
AB  - Microdamage density has been shown to increase with age in trabecular bone and is
      associated with decreased fracture toughness. Numerous studies of crack
      propagation in cortical bone have been conducted, but data in trabecular bone is
      lacking. In this study, propagation of severe, linear, and diffuse damage was
      examined in trabecular bone cores from the femoral head of younger (61.3+/-3.1
      years) and older (75.0+/-3.9 years) men and women. Using a two-step mechanical
      testing protocol, damage was first initiated with static uniaxial compression to
      0.8% strain then propagated at a normalized stress level of 0.005 to a strain
      endpoint of 0.8%. Coupling mechanical testing with a dual-fluorescent staining
      technique, the number and length/area of propagating cracks were quantified. It
      was found that the number of cycles to the test endpoint was substantially
      decreased in older compared to younger samples (younger: 77,372+/-15,984 cycles;
      older: 34,944+/-11,964 cycles, p=0.06). This corresponded with a greater number
      of severely damaged trabeculae expanding in area during the fatigue test in the
      older group. In the younger group, diffusely damaged trabeculae had a greater
      damage area, which illustrates an efficient energy dissipation mechanism. These
      results suggest that age-related differences in fatigue life of human trabecular
      bone may be due to differences in propagated microdamage morphology.

PMID- 21880318
TI  - The retention behaviour of polar compounds on zirconia based stationary phases
      under hydrophilic interaction liquid chromatography conditions.
AB  - The most separations in HILIC mode are performed on silica-based supports.
      Nevertheless, recently published results have indicated that the metal oxides
      stationary phases also possess the ability to interact with hydrophilic compounds
      under HILIC conditions. This paper primarily describes the retention behaviour of
      model hydrophilic analytes (4-aminobenzene sulfonic acid, 4-aminobenzoic acid, 4
      hydroxybenzoic acid, 3,4-diaminobenzoic acid, 3-aminophenol and 3-nitrophenol) on
      the polybutadine modified zirconia in HILIC. The results were simultaneously
      compared with a bare zirconia and a silica-based HILIC phase. The mobile phase
      strength, pH and the column temperature were systematically modified to assess
      their impact on the retention of model compounds. It was found that the retention
      of our model hydrophilic analytes on both zirconia phases was mainly governed by
      adsorption while on the silica-based HILIC phase partitioning was primarily
      involved. The ability of ligand-exchange interactions of zirconia surface with a
      carboxylic moiety influenced substantially the response of carboxylic acids on
      the elevated temperature as well as to the change of the mobile phase pH in
      contrast to the silica phase. However, no or negligible ligand-exchange
      interactions were observed for sulfanilic acid. The results of this study clearly
      demonstrated the ability of modified zirconia phase to retain polar acidic
      compounds under HILIC conditions, which might substantially enlarge the
      application area of the zirconia-based stationary phases.

PMID- 21880320
TI  - Development of high temperature comprehensive two-dimensional liquid
      chromatography hyphenated with infrared and light scattering detectors for
      characterization of chemical composition and molecular weight heterogeneities in
      polyolefin copolymers.
AB  - The application of high temperature comprehensive two-dimensional (2D) liquid
      chromatography for quantitative characterization of chemical composition and
      molecular weight (MW) heterogeneities in polyolefins is demonstrated in this
      study by separating a physical blend of isotactic-polypropylene, ethylene-random
      propylene copolymer, and high density polyethylene. The first dimension
      separation is based on adsorption liquid chromatography that fractionates the
      blend from low to high ethylene content. The second dimension is size-exclusion
      chromatography connected with light scattering (LS) and infrared (IR) detectors.
      The IR detector shows desired sensitivity and linearity for monitoring analyte
      concentrations in the eluent after 2D separations. In addition, the compositions
      of the analytes are also determined from the ratio of two IR absorbances at the
      specified wavelength regions, an absorbance for measuring the level of methyl
      groups in polyolefins and another absorbance for measuring concentration. The LS
      detector is used to determine absolute molecular weight of the analytes from the
      ratio of the light scattering signal to the IR concentration signal. The ability
      to obtain concentration, chemical composition, and MW of polyolefins after 2D
      separation provides new opportunities to discover structure-property
      relationships for polyolefins with complex structures/architectures.

PMID- 21880321
TI  - Resolving co-eluting chromatographic patterns by means of dissimilarity analysis
      in iterative target transformation factor analysis.
AB  - The initialization of concentration vector for iterative target transformation
      factor analysis (ITTFA) and identification of pure or key variables are the
      important issue in MCR. In this study, dissimilarity analysis and evolving factor
      analysis (EFA) are combined to find the selective or key variables and
      subsequently obtain initial estimates of the concentration vectors for resolution
      of gas chromatography/mass spectrometry (GC/MS) data by ITTFA. For systems
      containing components with highly similar mass spectra, a new constraint setting
      the elements out of elution window to 0 is used to improve convergence rate and
      accuracy of results. Tested by standard mixture of two wax esters and real GC/MS
      data of gasoline 97#, dissimilarity based ITTFA could obtain accurate results
      (average Dot product of concentration vectors, average deviation of peak area
      ratio and average similarity of mass spectra are 0.9929, 0.0228 and 981.0,
      respectively).

PMID- 21880322
TI  - Transcription factor proteomics: identification by a novel gel mobility shift
      three-dimensional electrophoresis method coupled with southwestern blot and high
      performance liquid chromatography-electrospray-mass spectrometry analysis.
AB  - Transcription factor (TF) purification and identification is an important step in
      elucidating gene regulatory mechanisms. In this study, we present two new
      electrophoretic mobility shift assay (EMSA)-based multi-dimensional
      electrophoresis approaches to isolate and characterize TFs, using detection with
      either southwestern or western blotting and HPLC-nanoESI-MS/MS analysis for
      identification. These new techniques involve several major steps. First, EMSA is
      performed with agents that diminish non-specific DNA-binding and the DNA-protein
      complex is separated by native PAGE gel. The gel is then electrotransferred to
      PVDF membrane and visualized by autoradiography. Next, the DNA-protein complex,
      which has been transferred onto the blot, is extracted using a detergent
      containing elution buffer. Following detergent removal, concentrated extract is
      separated by SDS-PAGE (EMSA-2DE), followed by in-gel trypsin digestion and HPLC
      nanoESI-MS/MS analysis, or the concentrated extract is separated by two
      dimensional gel electrophoresis (EMSA-3DE), followed by southwestern or western
      blot analysis to localize DNA binding proteins on blot which are further
      identified by on-blot trypsin digestion and HPLC-nanoESI-MS/MS analysis. Finally,
      the identified DNA binding proteins are further validated by EMSA-immunoblotting
      or EMSA antibody supershift assay. This approach is used to purify and identify
      GFP-C/EBP fusion protein from bacterial crude extract, as well as purifying AP1
      and CEBP DNA binding proteins from a human embryonic kidney cell line (HEK293)
      nuclear extract. AP1 components, c-Jun, Jun-D, c-Fos, CREB, ATF1 and ATF2 were
      successfully identified from 1.5 mg of nuclear extract (equivalent to 3*10(7)
      HEK293 cells) with AP1 binding activity of 750 fmol. In conclusion, this new
      strategy of combining EMSA with additional dimensions of electrophoresis and
      using southwestern blotting for detection proves to be a valuable approach in the
      identification of transcriptional complexes by proteomic methods.

PMID- 21880323
TI  - Study of the bioeffects of CdTe quantum dots on Escherichia coli cells.
AB  - Quantum dots (QDs) hold great potential for applications in nanomedicine,
      however, only a few studies investigate their toxic- and bio-effects. Using
      Escherichia coli (E. coli) cells as model, we found that CdTe QDs exhibited a
      dose-dependent inhibitory effect on cell growth by microcalorimetric technique
      and optical density (OD(600)). The growth rate constants (k) were determined,
      which showed that they were related to the concentration of QDs. The mechanism of
      cytotoxicity of QDs was also studied through the attenuated total reflection
      fourier transform infrared (ATR-FTIR) spectra, fluorescence (FL) polarization,
      and scanning electron microscopy (SEM). It was clear that the cell out membrane
      was changed or damaged by the addition of QDs. Taken together, the results
      indicated that CdTe QDs have cytotoxic effects on E. coli cells, and this effects
      might attribute to the damaged structure of the cell out membrane, thus QDs and
      by-products (free radicals, reactive oxygen species (ROS), and free Cd(2+)) which
      might enter the cells.

PMID- 21880324
TI  - Equilibrium clusters in concentrated lysozyme protein solutions.
AB  - We have studied the structure of salt-free lysozyme at 293 K and pH 7.8 using
      molecular simulations and experimental SAXS effective potentials between proteins
      at three volume fractions, phi=0.012, 0.033, and 0.12. We found that the
      structure of lysozyme near physiological conditions strongly depends on the
      volume fraction of proteins. The studied lysozyme solutions are dominated by
      monomers only for phi<=0.012; for the strong dilution 70% of proteins are in a
      form of monomers. For phi=0.033 only 20% of proteins do not belong to a cluster.
      The clusters are mainly elongated. For phi=0.12 almost no individual particles
      exits, and branched, irregular clusters of large extent appear. Our simulation
      study provides new insight into the formation of equilibrium clusters in charged
      protein solutions near physiological conditions.

PMID- 21880325
TI  - Rheological behaviour and spectroscopic investigations of cerium-modified AlO(OH)
      colloidal suspensions.
AB  - The rheological behaviour of aqueous suspensions of boehmite (AlO(OH)) modified
      with different Ce-salts (Ce(NO(3))(3), CeCl(3), Ce(CH(3)COO)(3) and
      Ce(2)(SO(4))(3)) was investigated at a fixed Ce/Al molar ratio (0.05). Freshly
      prepared boehmite suspensions were near-Newtonian and time-independent. A shear
      sensitive thixotropic network developed when Ce-salts with monovalent anions were
      introduced in the nanoparticle sols. The extent of particle aggregation
      dramatically increased with ageing for Ce(NO(3))(3) and CeCl(3) whereas an
      equilibrium value was reached with Ce(CH(3)COO)(3). The addition of
      Ce(2)(SO(4))(3) with divalent anions involved no thixotropy but rather a sudden
      phase separation. The combined data set of IRTF and DRIFT spectra indicated that
      free NO(3)(-) anions of peptized boehmite adsorb on the nanoparticle surface by H
      bond. The introduction of Ce-salts in the boehmite sol led to the coordination
      between Ce(3+) ions and NO(3)(-) anions adsorbed on boehmite i.e. to
      [Ce(NO(3))(4)(H(2)O)(x)](-) complex. Such coordination led to a thixotropic
      behaviour which was lower with Ce(NO(3))(3) compared to CeCl(3) and
      Ce(CH(3)COO)(3). In contrast, Ce(2)(SO(4))(3) formed insoluble complexes with
      dissolved aluminium species. The formation of H-bonded surface nitrate complexes
      was found to play a decisive role on the particle-particle interactions and
      consequently on the rheological behaviour of the sols.

PMID- 21880326
TI  - Comparing voice-therapy and vocal-hygiene treatments in dysphonia using a limited
      multidimensional evaluation protocol.
AB  - PURPOSE: This study evaluates the effectiveness of two different programs of
      voice-treatment on a heterogeneous group of dysphonic speakers and the stability
      of therapeutic progress for longterm follow-up post-treatment period, using a
      limited multidimensional protocol of evaluation. METHOD: Forty-two participants
      with voice disorders were randomly assigned to one of two groups. Participants in
      group 1 received voice-therapy and participants in group 2 received a vocal
      hygiene program. Vocal function was assessed before and after treatment. RESULTS:
      MANOVA analysis Pillai's trace test shows significant pre-post immediate
      differences between treatments in favor of direct-intervention. Repeated-measures
      ANOVAs display significant within subjects main effect for follow-up period in
      the 8 measures considered. Interaction effects of group*time are also found in
      five out of the eight continuous variables analyzed (3 aerodynamics-acoustic and
      2 self-rating), indicating differences between both treatments. Qualitative
      dimensions (perceptual, laryngoscopic and spectrographic assessments) also
      support voice-therapy superiority. CONCLUSIONS: Results of this study suggest
      superiority of a voice-therapy (direct treatment) approach over a vocal-hygiene
      program (indirect treatment). This advantage is on the majority of the 8
      continuous variables analyzed (aerodynamics, acoustic, and self-rating),
      including qualitative perceptual, laryngoscopic and spectrographic voice
      dimensions. The stability of changes is extended during a post-treatment follow
      up period. LEARNING OUTCOMES: (1) The reader should distinguish the advantage
      using one type of treatment or another in clinical contexts. (2) The reader must
      know the most important direct techniques used in clinical treatment of voice
      disorders.

PMID- 21880327
TI  - A computational approach to quantifiers as an explanation for some language
      impairments in schizophrenia.
AB  - We compared the processing of natural language quantifiers in a group of patients
      with schizophrenia and a healthy control group. In both groups, the difficulty of
      the quantifiers was consistent with computational predictions, and patients with
      schizophrenia took more time to solve the problems. However, they were
      significantly less accurate only with proportional quantifiers, like more than
      half. This can be explained by noting that, according to the complexity
      perspective, only proportional quantifiers require working memory engagement.
      LEARNING OUTCOMES: (1) Working memory deficits can be a source of language
      disorders in schizophrenia. (2) Processing of proportional quantifiers, like more
      than half or less than half involves working memory. (3) Patients with
      schizophrenia are less accurate only with proportional quantifiers, like more
      than half. (4) This result support the computational model of quantifiers
      processing.

PMID- 21880328
TI  - Motor coordination dynamics underlying graphic motion in 7- to 11-year-old
      children.
AB  - Using concepts and tools of a dynamical system approach in order to understand
      motor coordination underlying graphomotor skills, the aim of the current study
      was to establish whether the basic coordination dynamics found in adults is
      already established in children at elementary school, when handwriting is trained
      and eventually acquired. In the study, 45 children and 9 adults volunteered to
      copy two series of 13 ellipsoid shapes. These shapes were generated by
      manipulating the relative phase between 0 degrees  and 180 degrees  of two
      orthogonal oscillators in two orientations. Findings showed that although
      children from an early age onward and adults reproduced straight lines precisely
      (i.e., 0 degrees  and 180 degrees ), the former drew ellipsoid shapes in a less
      eccentric fashion than the latter (i.e., ~90 degrees  in all children rather than
      ~60 degrees  and 120 degrees  in adults). This tendency to write in a rounder
      fashion persists until 11 years of age, suggesting that the coordination dynamics
      underlying graphomotor skills and tentatively shaping the coordinated activity
      involved in adult handwriting appears only later, probably due to increasing
      constraints on speed.

PMID- 21880329
TI  - Positive Nikolsky sign due to Staphylococcal scaled skin syndrome.

PMID- 21880330
TI  - Is premedication for intubation of preterm infants the right choice?

PMID- 21880331
TI  - Central nervous system depression of neonates breastfed by mothers receiving
      oxycodone for postpartum analgesia.
AB  - OBJECTIVE: To quantify the incidence of central nervous system (CNS) depression
      in neonates breastfed by mothers medicated with oxycodone as compared with
      neonates whose breastfeeding mothers used codeine or acetaminophen only. STUDY
      DESIGN: We retrospectively compared 3 cohorts in 533 breastfeeding mother-infant
      pairs exposed to oxycodone (n = 139), codeine (n = 210), or acetaminophen only (n
      = 184). Standardized questionnaires were administered to mothers during the
      postpartum period to identify maternal and neonatal health outcomes temporally
      related to analgesia exposure. RESULTS: Maternal exposure to oxycodone during
      breastfeeding was associated with a 20.1% rate of infant CNS depression (28/139)
      compared with 0.5% in the acetaminophen group (1/184; P < .0001; OR, 46.16; 95%
      CI, 6.2-344.2) and 16.7% in the codeine group (35/210; P > .05; OR, 0.79; 95% CI,
      0.46-1.38). Mothers of neonates with symptoms in the oxycodone and codeine
      cohorts took significantly higher doses of medication compared with mothers of
      infants with no symptoms in the same cohorts (P = .0005 oxycodone; median, 0.4
      mg/kg/day; range, 0.03-4.06 mg/kg/day versus median, 0.15 mg/kg/day; range, 0.02
      2.25 mg/kg/day; codeine P < .001; median, 1.4 mg/kg/day; range, 0.7-10.5
      mg/kg/day versus 0.9 mg/kg/day; range, 0.18-5.8 mg/kg/day). Mothers were
      significantly more likely to experience sedative adverse effects from oxycodone
      as compared with codeine (P < .0001; OR, 17.62; 95% CI, 9.95-31.21). CONCLUSION:
      Oxycodone is not a safer alternative to codeine in breastfed infants.

PMID- 21880332
TI  - Analysis of slow- and fast-alpha band asymmetry during performance of a saccadic
      eye movement task: dissociation between memory- and attention-driven systems.
AB  - This study aimed at analyzing the relationship between slow- and fast-alpha
      asymmetry within frontal cortex and the planning, execution and voluntary control
      of saccadic eye movements (SEM), and quantitative electroencephalography (qEEG)
      was recorded using a 20-channel EEG system in 12 healthy participants performing
      a fixed (i.e., memory-driven) and a random SEM (i.e., stimulus-driven) condition.
      We find main effects for SEM condition in slow- and fast-alpha asymmetry at
      electrodes F3-F4, which are located over premotor cortex, specifically a negative
      asymmetry between conditions. When analyzing electrodes F7-F8, which are located
      over prefrontal cortex, we found a main effect for condition in slow-alpha
      asymmetry, particularly a positive asymmetry between conditions. In conclusion,
      the present approach supports the association of slow- and fast-alpha bands with
      the planning and preparation of SEM, and the specific role of these sub-bands for
      both, the attention network and the coordination and integration of sensory
      information with a (oculo)-motor response.

PMID- 21880333
TI  - Electrophysiological evaluation of spinocerebellar ataxias 1, 2 and 3.
AB  - INTRODUCTION: Subclinical neuropathy is an important feature of spinocerebellar
      ataxias (SCA) but the true prevalence and electrophysiological characteristics in
      genetically proven patients of SCA 1, 2 and 3 are largely unknown. METHODS: We
      prospectively compared the electrophysiological characteristics of neuropathy in
      61 genetically confirmed cases of SCA (SCA1=28, SCA2=16 and SCA3=17). Nerve
      conduction studies were performed in at least one sensory and one motor nerve, in
      right upper and lower limb using standard methods. RESULTS: The mean age of
      patients and duration of illness were comparable among SCA groups (mean age
      (years): SCA1-34.1+/-12.7, SCA2-35.2+/-13.9 and SCA3-38.1+/-11.3; mean duration
      (years): SCA1-5.4, SCA2-6.1, and SCA3-4.4). Electrophysiological evidence of
      neuropathy was highest in SCA1 (96.4%), followed by SCA3 (94.1% and SCA2 (87.5%).
      A mixed sensorimotor neuropathy was commonly observed in all the subgroups (SCA1
      78.6%, SCA2-50%, and SCA3-41.2%). Pure sensory neuropathy was most common in SCA3
      (55.9%), followed by 31.3% in SCA2 and 17.9% in SCA1. Pure motor neuropathy was
      uncommon (6.3% in SCA2 and none in SCA1 and SCA3). CONCLUSIONS:
      Electrophysiological evidence of mixed sensorimotor and pure sensory neuropathy
      is seen in all the three subtypes of SCAs, while pure motor neuropathy is
      distinctly uncommon.

PMID- 21880334
TI  - Sleep-wake changes in the premotor stage of Parkinson disease.
AB  - Longitudinal studies in Parkinson disease (PD) have shown that the prevalence of
      sleep disorders increases with advanced disease. However, two sleep disorders,
      namely excessive daytime sleepiness (EDS) and REM sleep behavior disorder (RBD)
      have been described to antedate the development of the classical motor signs and
      symptoms of PD. One epidemiological study from the Honolulu-Asia Aging Study
      showed that aging men who reported "being sleepy most of the daily" had a
      threefold excess risk for developing PD after a seven-year follow-up. The origin
      and nature of EDS were not investigated. This study needs to be replicated. More
      robust data exist regarding RBD as the first manifestation of PD. RBD subjects
      commonly develop parkinsonism and cognitive impairment with time. Patients with
      the idiopathic form of RBD with decreased striatal dopamine transporters imaging,
      substantia nigra hyperechogenicity and hyposmia have an increased short-term risk
      for developing the classical motor, dysautonomic and cognitive symptoms of a
      synucleinopathy. Patients with idiopathic RBD, particularly those with abnormal
      subclinical features seen in the synucleinopathies such as decreased striatal
      dopamine transporters uptake, are the ideal population to be tested with disease
      modifying agents in order to stop or slow down neurodegeneration in the brain.

PMID- 21880335
TI  - Initial neuropsychological impairments in patients with the E46K mutation of the
      alpha-synuclein gene (PARK 1).
AB  - INTRODUCTION: In 2004 we described the mutation E46K of the alpha-Synuclein
      (SNCA). These patients show Parkinson's disease with early cognitive impairment,
      sleep disorders and autonomic dysfunction. OBJECTIVE: The main objective is to
      identify early neuropsychological impairments in patients with the E46K mutation.
      METHODS: This is a longitudinal neuropsychological study of 4 of the 5 surviving
      patients with E46K mutation by semi-structured interviews and the following
      scales: Mattis Dementia Rating Scale (MDRS), semantic and phonemic verbal fluency
      tests (VFT), Benton Visual Retention Test (BVRT), Stroop Test (STROOP), Clock
      drawing test (CLOCK), WAIS III Letter and Number sequencing (WAIS III LN), Rey
      Auditory Verbal Learning Test (RAVLT) and Benton Judgement of Line Orientation
      Test (BJLOT). Motor status was assessed by UPDRS III. RESULTS: Motor status:
      Patients 1, 2 and 3 present mild to moderate Parkinson disease of 7, 8 and 3years
      of evolution respectively, patient 4 is asymptomatic. Cognitive status: Patient 2
      and 3 both refer cognitive decline while patient 1 presents no cognitive
      complaints, however they all show a progressive cognitive decline across various
      tasks. Tests of frontal function showed the first alterations in all patients but
      fluctuate. The first cognitive complaints coincide with deterioration of tasks of
      posterior cortical basis. Patient 4 presents a normal performance on all tests.
      Patient 1, 2 and 3 have all presented visual hallucinations. CONCLUSIONS: A
      fluctuating frontal impairment is observed at early stages. Prominent
      visuospatial alterations and visual hallucinations suggest that posterior
      cortical dysfunction might be a distinct early feature of the cognitive
      impairment observed in patients with this mutation.

PMID- 21880336
TI  - Efficacy and safety of subcutaneous interferon beta-1a in relapsing-remitting
      multiple sclerosis: further outcomes from the IMPROVE study.
AB  - BACKGROUND: The IMPROVE study demonstrated that the fetal bovine serum (FBS)- and
      human serum albumin (HSA)-free formulation of subcutaneous (sc) interferon (IFN)
      beta-1a had beneficial effects on the numbers of combined unique active magnetic
      resonance imaging (MRI) lesions in relapsing-remitting multiple sclerosis (RRMS).
      Here we report additional MRI endpoints (including post hoc analyses), and
      clinical efficacy, safety, and immunogenicity outcomes. METHODS: Patients with
      active RRMS were randomized (2:1) to IFN beta-1a, 44 mcg sc three times weekly
      (tiw) (n=120), or placebo (n=60), for 16 weeks (double-blind phase). All patients
      then received IFN beta-1a, 44 mcg sc tiw, for 24 weeks (rater-blind phase).
      Patients underwent MRI brain scans every 4 weeks. RESULTS: Compared with placebo,
      there was a 68% reduction in the mean cumulative number of new gadolinium
      enhancing lesions with IFN beta-1a as early as week 4 (p<0.001), and a 53%
      reduction in the mean cumulative number of new T2 lesions as early as week 8
      (p=0.025; post hoc analyses). During the 16-week double-blind phase, the relapse
      rate was 0.14 (95% confidence interval [CI] 0.09-0.23) with IFN beta-1a and 0.33
      (95% CI 0.22-0.52) with placebo (p=0.010). Safety outcomes were consistent with
      those expected with IFN-beta treatment. CONCLUSIONS: The FBS/HSA-free formulation
      of sc IFN beta-1a has a beneficial impact on MRI and efficacy outcomes as early
      as 4 weeks after treatment initiation in patients with RRMS and has a safety
      profile consistent with previous trials of sc IFN beta-1a.

PMID- 21880337
TI  - Conjugates of abscisic acid, brassinosteroids, ethylene, gibberellins, and
      jasmonates.
AB  - Phytohormones, including auxins, abscisic acid, brassinosteroids, cytokinins,
      ethylene, gibberellins, and jasmonates, are involved in all aspects of plant
      growth, and developmental processes as well as environmental responses. However,
      our understanding of hormonal homeostasis is far from complete. Phytohormone
      conjugation is considered as a part of the mechanism to control cellular levels
      of these compounds. Active phytohormones are changed into multiple forms by
      acylation, esterification or glycosylation, for example. It seems that conjugated
      compounds could serve as pool of inactive phytohormones that can be converted to
      active forms by de-conjugation reactions. Some conjugates are thought to be
      temporary storage forms, from which free active hormones can be released after
      hydrolysis. It is also believed that conjugation serves functions, such as
      irreversible inactivation, transport, compartmentalization, and protection
      against degradation. The nature of abscisic acid, brassinosteroid, ethylene,
      gibberellin, and jasmonate conjugates is discussed.

PMID- 21880338
TI  - Beta-D-(1->4)-galactan-containing side chains in RG-I regions of pectic
      polysaccharides from Biophytum petersianum Klotzsch. contribute to expression of
      immunomodulating activity against intestinal Peyer's patch cells and macrophages.
AB  - The aerial parts of the medicinal plant Biophytum petersianum have a long
      tradition for being used in Mali and other West-African countries against various
      ailments such as wound healing and malaria. Previous studies on polysaccharides
      from water extracts of the aerial parts showed the presence of pectic like
      polymers with an effect on the human complement system as well as the ability to
      activate macrophages and dendritic cells. The present study shows that pectic
      polysaccharide fragments (BPII.1 and BPII.2) as well as the original pectic
      polysaccharide (BPII) expressed immunomodulating activity against Peyer's patch
      immunocompetent cells. Exo-beta-D-(1->3)-galactanase digestion succeeded to
      decrease IL-6 production enhancing activity against Peyer's patch cells of
      BPII.2, but the activity of BPII.1 did not decrease. Endo-beta-D-(1->4)
      galactanase digestion reduced the activities of both BPII.1 and BPII.2. BPII.1
      and BPII.2 also stimulated IL-6 production enhancing activity against
      macrophages, and the activities of both pectic fragments were significantly
      decreased by either enzymic digestion with exo-beta-D-(1->3)-galactanase or endo
      beta-D-(1->4)-galactanase. Trimming of terminal GlcA by exo-beta-D-glucuronidase
      digestion did not affect IL-6 production enhancing activity against macrophages
      of both pectic fragments. Methylation analyses of endo-beta-D-(1->4)-galactanase
      digestion products showed the characteristic decrement of 4-linked Gal residues
      in the pectic fragments. These results suggest that beta-D-(1->4)-galactan
      containing side chains in BPII.1 and BPII.2 play an important role for expression
      of immunomodulating activity against both Peyer's patch immunocompetent cells and
      macrophages in addition to beta-D-(1->3,6)-galactan chains.

PMID- 21880339
TI  - Escherichia coli O115 forms fewer attaching and effacing lesions in the ovine
      colon in the presence of E. coli O157:H7.
AB  - Escherichia coli O115 has been isolated from healthy sheep and was shown to be
      associated with attaching-effacing (AE) lesions in the large intestine. Following
      previous observations of interactions between E. coli O157 and O26, the aim of
      the present study was to assess what influence an O115 AE E. coli (AEEC) would
      have on E. coli O157 colonisation in vitro and in vivo. We report that E. coli
      O115- and O157-associated AE lesions were observed on HEp-2 cells and on the
      mucosa of ligated ovine spiral colon. In single strain inoculum, E. coli O115
      associated intimately with HEp-2 cells and the spiral colon in greater numbers
      than E. coli O157:H7. However, in mixed inoculum studies, the number of E. coli
      O115 AE lesions was significantly reduced suggesting negative interference by E.
      coli O157. Use of the ligated colon model in the present work has allowed in
      vitro observations to be extended and confirmed whilst using a minimum of
      experimental animals. The findings support a hypothesis that some AEEC can
      inhibit adhesion of other AEEC in vivo. The mechanisms involved may prove to be
      of utility in the control of AE pathovars.

PMID- 21880340
TI  - Analysis of nucleotides 13-96 of the human parainfluenza virus type 3 antigenomic
      promoter reveals positive- and negative-acting replication elements.
AB  - During replication of human parainfluenza virus type 3 (HPIV3), the 96-nucleotide
      antigenomic promoter (AGP) of HPIV3 directs the synthesis of genomic RNA.
      Previous work showed that nucleotides 1-12 were critical in promoting replication
      of an HPIV3 minireplicon, but nucleotides 13-96 were not investigated. In this
      study, the role of nucleotides 13-96 in AGP function was analyzed by creating and
      assaying mutations in an HPIV3 minireplicon. A replication promoting element
      known as promoter element II (nt 79-96) was confirmed in the HPIV3 AGP.
      Additionally, nucleotides 13-39 were found to constitute an additional positive
      acting cis-element. However, detailed analysis of the 13-39 element revealed a
      complicated control element with both stimulatory and repressing elements.
      Specifically, nucleotides 21-28 were shown to repress RNA replication, while
      flanking sequences had a stimulatory effect.

PMID- 21880341
TI  - Fluid shear influences on the performance of hydraulic flocculation systems.
AB  - Gravity driven hydraulic flocculators that operate in the absence of reliable
      electric power are better suited to meet the water treatment needs of green
      communities, resource-poor communities, and developing countries than
      conventional mechanical flocculators. However, current understanding regarding
      the proper design and operation of hydraulic flocculation systems is
      insufficient. Of particular interest is the optimal fluid shear level needed to
      produce low turbidity water. A hydraulic tube flocculator was used to study how
      fluid shear levels affect the settling properties of a flocculated alum-kaolin
      suspension. A Flocculation Residual Turbidity Analyzer (FReTA) was used to
      quantitatively compare the sedimentation velocity distributions and the post
      sedimentation residual turbidities of the flocculated suspensions to see how they
      were affected by varying fluid shear, G, and hydraulic residence time, theta,
      while holding collision potential, Gtheta, constant. Results show that floc
      breakup occurred at all velocity gradients evaluated. High floc settling
      velocities were correlated with low residual turbidities, both of which were
      optimized at low fluid shear levels and long fluid residence times. This study
      shows that, for hydraulic flocculation systems under the conditions described in
      this paper, low turbidity water is produced when fluid shear is kept at a
      minimum. Use of the product Gtheta for design of laminar flow tube flocculators
      is insufficient if residual turbidity is used as the metric for performance. At
      any Gtheta within the range tested in this study, best performance is obtained
      when G is small and theta is long.

PMID- 21880342
TI  - Nitrification and potential control mechanisms in simulated premises plumbing.
AB  - Indigenous drinking water organisms were used to establish nitrification in glass
      reactors containing copper or polyvinyl chloride (PVC) surfaces. The reactors
      were fed soil-derived humics as the organic carbon source and ammonium sulfate as
      the nitrogen source in biologically treated tap water. Water in the reactors was
      stagnant for 8 h and then flowed for 5 min to simulate conditions in household
      plumbing. Following the establishment of complete nitrification (conversion of
      ammonia to nitrate) in both reactor types, various inhibitors of nitrification
      were tested followed by a period where recovery of nitrification was observed. In
      one PVC reactor, copper was gradually introduced up to 1.3 ppm. To ensure that
      most of the copper was in the ionic form, the pH of the influent was then
      gradually lowered to 6.6. No significant change in nitrification was observed in
      the presence of copper. Chlorite was introduced into copper and PVC reactors at
      doses increasing from 0.2 ppm to 20 ppm. There was limited effect on the PVC
      system and inhibition in the copper reactor only at 20 ppm. Chloramine was tested
      at chlorine to ammonia ratios ranging from 0.5:1 to 5:1. Nitrification activity
      was impacted significantly at a 5:1 ratio and ultimately stopped, with the
      fastest response being in the copper system. Whenever a control mechanism was
      tested, there was increased release of copper from the reactors with copper
      coupons. In all cases, nitrification recovered when inhibitors were removed but
      the rates of recovery differed depending on the treatment method and coupon
      surface.

PMID- 21880343
TI  - Nitrate removal, communities of denitrifiers and adverse effects in different
      carbon substrates for use in denitrification beds.
AB  - Denitrification beds are containers filled with wood by-products that serve as a
      carbon and energy source to denitrifiers, which reduce nitrate (NO(3)(-)) from
      point source discharges into non-reactive dinitrogen (N(2)) gas. This study
      investigates a range of alternative carbon sources and determines rates,
      mechanisms and factors controlling NO(3)(-) removal, denitrifying bacterial
      community, and the adverse effects of these substrates. Experimental barrels (0.2
      m(3)) filled with either maize cobs, wheat straw, green waste, sawdust, pine
      woodchips or eucalyptus woodchips were incubated at 16.8  degrees C or 27.1 
      degrees C (outlet temperature), and received NO(3)(-) enriched water (14.38 mg N
      L(-1) and 17.15 mg N L(-1)). After 2.5 years of incubation measurements were made
      of NO(3)(-)-N removal rates, in vitro denitrification rates (DR), factors
      limiting denitrification (carbon and nitrate availability, dissolved oxygen,
      temperature, pH, and concentrations of NO(3)(-), nitrite and ammonia), copy
      number of nitrite reductase (nirS and nirK) and nitrous oxide reductase (nosZ)
      genes, and greenhouse gas production (dissolved nitrous oxide (N(2)O) and
      methane), and carbon (TOC) loss. Microbial denitrification was the main mechanism
      for NO(3)(-)-N removal. Nitrate-N removal rates ranged from 1.3 (pine woodchips)
      to 6.2 g N m(-3) d(-1) (maize cobs), and were predominantly limited by C
      availability and temperature (Q(10) = 1.2) when NO(3)(-)-N outlet concentrations
      remained above 1 mg L(-1). The NO(3)(-)-N removal rate did not depend directly on
      substrate type, but on the quantity of microbially available carbon, which
      differed between carbon sources. The abundance of denitrifying genes (nirS, nirK
      and nosZ) was similar in replicate barrels under cold incubation, but varied
      substantially under warm incubation, and between substrates. Warm incubation
      enhanced growth of nirS containing bacteria and bacteria that lacked the nosZ
      gene, potentially explaining the greater N(2)O emission in warmer environments.
      Maize cob substrate had the highest NO(3)(-)-N removal rate, but adverse effects
      include TOC release, dissolved N(2)O release and substantial carbon consumption
      by non-denitrifiers. Woodchips removed less than half of NO(3)(-) removed by
      maize cobs, but provided ideal conditions for denitrifying bacteria, and adverse
      effects were not observed. Therefore we recommend the combination of maize cobs
      and woodchips to enhance NO(3)(-) removal while minimizing adverse effects in
      denitrification beds.

PMID- 21880344
TI  - Mechanism for sulfur acquisition by the alkanesulfonate monooxygenase system.
AB  - The bacterial alkanesulfonate monooxygenase system is involved in the acquisition
      of sulfur from organosulfonated compounds during limiting sulfur conditions. The
      reaction relies on an FMN reductase to supply reduced flavin to the monooxygenase
      enzyme. The reaction catalyzed by the alkanesulfonate monooxygenase enzyme
      involves the carbon-sulfur bond cleavage of a wide range of organosulfonated
      compounds. A C4a-(hydro)peroxyflavin is the oxygenating intermediate in the
      mechanism of desulfonation by the alkanesulfonate monooxygenase. This review
      discusses the physiological importance of this system, and the individual kinetic
      parameters and mechanistic properties of this enzyme system.

PMID- 21880345
TI  - Occurrence and distribution of pharmaceuticals in surface water, suspended solids
      and sediments of the Ebro river basin, Spain.
AB  - The occurrence of 43 pharmaceuticals belonging to predominant therapeutic classes
      and their distribution in surface water, suspended solids and sediments has been
      investigated in the Ebro river basin in the Northeast of Spain. WWTP effluents
      were found to be a main source of contamination and the spatial distribution was
      affected by the river flow at the sampling point and corresponding dilution
      factor, resulting in higher concentrations and higher loads in small tributary
      rivers than in the Ebro river. The study showed that some compounds are
      preferentially found bound to suspended solids and not detected in river water.
      Generally, compounds with basic characteristics (pKa > 7) showed higher tendency
      to bind to suspended solids. The sediment samples generally presented lower
      concentrations than suspended solids.

PMID- 21880346
TI  - Development of an analytical strategy based on liquid chromatography-high
      resolution mass spectrometry for measuring perfluorinated compounds in human
      breast milk: application to the generation of preliminary data regarding
      perinatal exposure in France.
AB  - Perfluorinated compounds (PFCs) are man-made chemicals for which endocrine
      disrupting properties and related possible side effects on human health have been
      reported, particularly in the case of an exposure during the early stages of
      development, (notably the perinatal period). Existing analytical methods
      dedicated to PFCs monitoring in food and/or human fluids are currently based on
      liquid chromatography coupled to tandem mass spectrometry, and were recently
      demonstrated to present some limitations in terms of sensitivity and/or
      specificity. An alternative strategy dedicated to the analysis of fourteen PFCs
      in human breast milk was proposed, based on an effective sample preparation
      followed by a liquid chromatography coupled to high resolution mass spectrometry
      measurement (LC-HRMS). This methodology confirmed the high interest for HRMS
      after negative ionization for such halogenated substances, and finally permitted
      to reach detection limits around the pg mL(-1) range with an outstanding signal
      specificity compared to LC-MS/MS. The proposed method was applied to a first set
      of 30 breast milk samples from French women. The main PFCs detected in all these
      samples were PFOS and PFOA with respective median values of 74 (range from 24 to
      171) and 57 (range from 18 to 102) pg mL(-1), respectively. These exposure data
      appeared in the same range as other reported values for European countries.

PMID- 21880347
TI  - Formation and mitigation of PCDD/Fs in iron ore sintering.
AB  - The sintering of iron ore is presently a significant industrial source of
      polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDD/Fs)
      worldwide owing to the fundamental requirement of the operation of a high
      temperature process to pre-treat fines and to recycle plant by-products arising
      from the integrated iron and steelworks. The process is a noteworthy contributor
      of PCDD/F indirectly due to decreasing PCDD/F releases from municipal solid waste
      incineration. Commonly PCDD/F formation from the process is associated with the
      addition of oily mill scales although raw material containing a combination of C,
      Cl and specific metal catalyst has been shown to drastically increase PCDD/F
      formation in the process. The degenerate graphitic structure of carbon present in
      coke fuel and soot formed and the chemistry of catalytic metals and Cl are
      important factors. A review on PCDD/F emission in this process has been carried
      out, including examination of its formation mechanism, congener distribution,
      contributing factors and mitigation strategies, with emphasis on the use of
      inhibiting compound to achieve suppression. A detailed analysis of the de novo
      and precursor theories of formation and the contributing factor is given since
      the subject of PCDD/F formation is still controversial. The de novo formation
      pathway identified in sinter plants and controlled studies performed in the
      laboratory as well as at pilot-scale are discussed; where appropriate, a
      comparison is drawn between sintering and other thermal processes emitting
      PCDD/Fs. Summary of the latest developments in PCDD/F downstream abatement
      strategies presently employed in full scale industrial plants is provided.
      Potential inhibiting compounds are discussed in terms of their mode of action and
      merits under sintering conditions.

PMID- 21880348
TI  - Modeling batch leaching behavior of arsenic and selenium from bituminous coal fly
      ashes.
AB  - Correctly predicting the leaching potential of arsenic (As) and selenium (Se) is
      critical for assessing the environmental impact of coal fly ash. This study
      investigated the impacts of several key environmental factors, including pH,
      leaching time, and ash washing on the batch leaching behavior of As and Se from
      bituminous coal fly ashes. The experimental results demonstrated that As and Se
      leaching from fly ash increased beyond the minimal leaching pH ranges. Increasing
      leaching time increased As leaching but decreased Se leaching in the alkaline pH
      condition. A speciation-based adsorption model was used to quantify the batch
      leaching data, and determine the intrinsic leaching parameters including the
      total batch leachable mass and the adsorption constant of As or Se. The modeling
      approach was validated by correctly predicting the independent batch leaching
      data in a broad pH range and a different L/S condition. Experimental and modeling
      results also demonstrated that ash washing and ash aging (longer leaching time)
      did not change the adsorption constants of As and Se on the ash surface. However,
      ash washing could increase the availability of As and Se for leaching.

PMID- 21880349
TI  - Concentrations, spatial distributions and congener profiles of polychlorinated
      biphenyls in soils from a coastal city--Tianjin, China.
AB  - A total of 82 surface soil samples collected from central urban sites,
      surrounding rural sites, coastal sites and background sites in Tianjin were
      analyzed for 84 PCB congeners. The mean values of total PCBs concentrations for
      surrounding rural sites, central urban sites, coastal sites, background sites and
      the whole Tianjin region were 4.45, 3.20, 12.65, 1.96 and 4.02 ng g(-1),
      respectively. No "urban fractionation effect" was found in Tianjin, which
      reflected the influence of local emission sources for PCBs such as industries and
      township enterprises in surrounding rural sites. In contrast, a "primary
      fractionation effect" was found in Tianjin region. The PCBs concentrations for
      whole Tianjin region showed a strong east-west gradient and the percentages of
      lighter molecular weight PCBs homologs (sum of di- to tetra-PCBs) to the total
      PCBs concentrations increased from east to west. The seven indicator PCBs
      concentrations were well correlated with the total PCBs concentrations with the
      correlation coefficients as 0.76 for Tianjin region and 0.74 for central urban
      sites, respectively. Predominant PCB homolog groups were penta- and tri-PCBs for
      Tianjin region. 10 dioxin-like PCBs concentrations were well correlated with
      total PCBs concentrations for all the sampling sites (R=0.79, P<0.0001). The TEQ
      concentrations for 10 dioxin-like PCBs were 5.3424 ng kg(-1) for Tianjin region
      and showed a strong east to west gradient. The spatial distribution of PCBs
      levels, homolog composition patterns and TEQ concentrations were all obviously
      influenced by local emission sources for PCBs in the east part of Tianjin region.

PMID- 21880350
TI  - Intensification of volatile organic compounds mass transfer in a compact scrubber
      using the O3/H2O2 advanced oxidation process: kinetic study and hydroxyl radical
      tracking.
AB  - This study assesses the potential of ozonation and advanced oxidation process
      O(3)/H(2)O(2) to enhance the dimethyldisulfide (DMDS) mass transfer in a compact
      chemical scrubber developed for air treatment applications. Theoretical
      calculations, through Hatta number and enhancement factor evaluations for two
      parallel irreversible reactions, were compared to experimental data and enabled
      the description of the mass transfer mechanisms. These calculations required the
      determination of the kinetic constant of the DMDS oxidation by molecular ozone (
      [Formula: see text] ) and the measurement of the hydroxyl radical concentration
      within the scrubber. The competitive kinetic method using the 1,2
      dihydroxybenzene (resorcinol) enabled to determine a value of the kinetic
      constant  [Formula: see text]  of 1.1*10(6)M(-1)s(-1) at 293K. Then, experiments
      using para-chlorobenzoic acid in solution allowed measuring the average hydroxyl
      concentration in the scrubber between the inlet and the outlet depending on the
      chemical conditions (pH and inlet O(3) and H(2)O(2) concentrations). High
      hydroxyl radical concentrations (10(-8)M) and ratio of the HO degrees -to-O(3)
      exposure (R(ct)~10(-4)) were put in evidence.

PMID- 21880351
TI  - Climate change - An uncertainty factor in risk analysis of contaminated land.
AB  - Metals frequently occur at contaminated sites, where their potential toxicity and
      persistence require risk assessments that consider possible long-term changes.
      Changes in climate are likely to affect the speciation, mobility, and risks
      associated with metals. This paper provides an example of how the climate effect
      can be inserted in a commonly used exposure model, and how the exposure then
      changes compared to present conditions. The comparison was made for cadmium (Cd)
      exposure to 4-year-old children at a highly contaminated iron and steel works
      site in southeastern Sweden. Both deterministic and probabilistic approaches
      (through probability bounds analysis, PBA) were used in the exposure assessment.
      Potential climate-sensitive variables were determined by a literature review.
      Although only six of the total 39 model variables were assumed to be sensitive to
      a change in climate (groundwater infiltration, hydraulic conductivity, soil
      moisture, soil:water distribution, and two bioconcentration factors), the total
      exposure was clearly affected. For example, by altering the climate-sensitive
      variables in the order of 15% to 20%, the deterministic estimate of exposure
      increased by 27%. Similarly, the PBA estimate of the reasonable maximum exposure
      (RME, defined as the upper bound of the 95th percentile) increased by almost 20%.
      This means that sites where the exposure in present conditions is determined to
      be slightly below guideline values may in the future exceed these guidelines, and
      risk management decisions could thus be affected. The PBA, however, showed that
      there is also a possibility of lower exposure levels, which means that the
      changes assumed for the climate-sensitive variables increase the total
      uncertainty in the probabilistic calculations. This highlights the importance of
      considering climate as a factor in the characterization of input data to exposure
      assessments at contaminated sites. The variable with the strongest influence on
      the result was the soil:water distribution coefficient (Kd).

PMID- 21880352
TI  - Effectiveness and safety of thromboprophylaxis with enoxaparin in medical
      inpatients.
AB  - BACKGROUND: Venous thromboembolism (VTE) includes deep vein thrombosis and
      pulmonary embolism. Although effective prophylaxis exists for medical patients,
      there is little information outside of clinical trials. We will analyze our
      experience in the prophylaxis of VTE with enoxaparin in hospitalized medical
      patients. MATERIAL AND METHODS: We studied all of the patients >=15 years
      admitted for emergency care to all of the medical departments of the hospital,
      except for the Hematology Department, between 1/April/1999 and 31/December/2005.
      The patients' age, sex, Charlson comorbidity index (CCI), whether they received
      prophylaxis with enoxaparin or not, dose, VTE, bleeding, thrombocytopenia, and
      mortality were analyzed. RESULTS: 40,349 patients were included, of which 55.87%
      were male, with an average age of 67.56, and an average CCI of 4.99. There were
      19,834 patients who did not receive prophylaxis for which the rate of incidence
      of VTE was 0.61%, mortality 8.75%, bleeding 1.38%, and thrombocytopenia 0.04%.
      Prophylactic enoxaparin was administered to 20,515 patients, for which the rate
      of incidence of VTE was 0.44%, mortality 10.71%, bleeding 1.1%, and
      thrombocytopenia 0.04%. The adjusted Odds Ratio (OR) for VTE was 0.65 (95%
      confidence interval [95% CI] 0.49 to 0.87). The adjusted OR for mortality was
      0.84 (95% CI 0.78 to 0.9). With the adjusted data, the number needed to treat
      (NNT) for VTE was 470.3 (95% CI 278.4 to 1413.3), and the NNT for mortality was
      77.2 (95% CI 54.6 to 130.3). CONCLUSION: Thromboprophylaxis with enoxaparin in
      hospitalized medical patients is associated with a lower incidence of VTE and
      mortality, and is safe.

PMID- 21880353
TI  - Comparative evaluation of Tissue factor and Thrombomodulin activity changes
      during normal and idiopathic early and late foetal loss: the cause of
      hypercoagulability?
AB  - Various components of the coagulation and fibrinolytic pathways are involved in
      normal embryonic implantation, trophoblast invasion, placentation, and recurrent
      miscarriages are characterized by defective placentation and microthrombi in the
      placental vasculature. Although recurrent miscarriage is a heterogeneous
      condition the relationship between abnormalities in the haemostatic pathways and
      pregnancy outcome is increasingly recognized. The challenge we face is how to
      discriminate between women who are destined to miscarry from those whose
      pregnancy will be successful. Considering the crucial role of thrombomodulin and
      tissue factor in coagulation and in embryonic development, we have performed a
      study using specific assays for thrombomodulin, tissue factor activity and
      procoagulant phospholipids in association with other parameters in 30 early
      (under 12weeks) and 32 late (over 22weeks) pregnancy loss women and compared them
      with 62 normal pregnancy women and 35 non-pregnant women. Plasma levels of tissue
      factor activity, thrombomodulin activity, and procoagulant phospholipids were
      significantly higher in patients than in control subjects. In addition the tissue
      factor activity/free tissue factor pathway inhibitor ratio was higher in patients
      than in controls. Interestingly, patients with late pregnancy loss had higher
      tissue factor activity/free tissue factor pathway inhibitor ratios than patients
      with early pregnancy loss. The combinations of these different parameters reveal
      an increase in procoagulant activity which could be secondary to endothelial
      damage or coagulation activation and then are involved in the pathogenesis of
      pregnancy loss. Their simultaneous measurement of these activities might provide
      a new tool to assess the prognosis of pregnancy loss.

PMID- 21880354
TI  - Subepithelial collagen deposition, profibrogenic cytokine gene expression, and
      changes after prolonged fluticasone propionate treatment in adult eosinophilic
      esophagitis: a prospective study.
AB  - BACKGROUND: Recent research shows that both pediatric and adult patients with
      eosinophilic esophagitis (EoE) experience esophageal remodeling marked by
      increased collagen deposition in which TGF-beta plays an important role. However,
      limited data are available on the intensity and reversibility of fibrous
      remodeling in adults with EoE. OBJECTIVE: We sought to analyze differences in
      collagen deposition in the lamina propria (LP) and profibrogenic cytokine gene
      expression along with other changes induced by prolonged treatment with
      fluticasone propionate in adults with EoE. METHODS: Ten adults given consecutive
      diagnoses of EoE were studied prospectively. Deep esophageal biopsy specimens
      were obtained before and after 1 year of treatment with fluticasone propionate.
      Collagen deposition in the LP was assessed in tissue sections with the aid of the
      Masson trichrome technique. IL5, TGFB1, fibroblast growth factor 9 (FGF9), and
      CCL18 gene expression was quantified through real-time PCR. EoE results were
      compared among samples from 10 adult patients with gastroesophageal reflux
      disease and 10 control subjects with healthy esophagi. RESULTS: Patients with EoE
      showed a significant increase in subepithelial collagen deposition; this
      correlated positively with eosinophil density in the LP and the patient's age.
      Prolonged steroid treatment induced a nonsignificant reduction in subepithelial
      fibrosis, which remained significantly higher than in control subjects.
      Profibrogenic cytokine gene expression also increased in patients with EoE, with
      IL5 (P < .001), FGF9 (P = .005), and CCL18 (P = .008) all significantly
      upregulated. After 1 year of treatment, a reduction was observed in gene
      expression; for CCL18 expression, this decrease was statistically significant (P
      < .001). CONCLUSIONS: Esophageal remodeling is associated with upregulated gene
      expression of profibrogenic cytokines in adults with EoE. Prolonged treatment
      with fluticasone propionate leads to a nonsignificant reduction in subepithelial
      collagen deposition accompanied by downregulation of profibrogenic cytokine gene
      expression, with that of CCL18 being especially significant.

PMID- 21880355
TI  - Real time neutron diffraction and NMR of the Empress II glass-ceramic system.
AB  - OBJECTIVE: This study reports real time neutron diffraction on the Empress II
      glass-ceramic system. METHODS: The commercial glass-ceramics was characterized by
      real time neutron diffraction, 31P and 29Si solid-state MAS-NMR, DSC and XRD.
      RESULTS: On heating, the as-received glass ceramic contained lithium disilicate
      (Li2Si2O5), which melted with increasing temperature. This was revealed by
      neutron diffraction which showed the Bragg peaks for this phase had disappeared
      by 958 degrees C in agreement with thermal analysis. On cooling lithium
      metasilicate (Li2SiO3) started to form at around 916 degrees C and a minor phase
      of cristobalite at around 852 degrees C. The unit cell volume of both Li-silicate
      phases increased linearly with temperature at a rate of +17*10-3 A3. degrees C-1.
      Room temperature powder X-ray diffraction (XRD) of the material after cooling
      confirms presence of the lithium metasilicate and cristobalite as the main phases
      and shows, in addition, small amount of lithium disilicate and orthophosphate.
      31P MAS-NMR reveals presence of the lithiorthophosphate (Li3PO4) before and after
      heat treatment. The melting of lithium disilicate on heating and crystallisation
      of lithium metasilicate on cooling agree with endothermic and exotermic features
      respectively observed by DSC. 29Si MAS-NMR shows presence of lithium disilicate
      phase in the as-received glass-ceramic, though not in the major proportion, and
      lithium metasilicate in the material after heat treatment. Both phases have
      significantly long T1 relaxation time, especially the lithium metasilicate,
      therefore, a quantitative analysis of the 29Si MAS-NMR spectra was not attempted.
      Significance. The findings of the present work demonstrate importance of the
      commercially designed processing parameters in order to preserve desired
      characteristics of the material. Processing the Empress II at a rate slower than
      recommended 60 degrees C min-1 or long isothermal hold at the maximal processing
      temperature 920 degrees C can cause crystallization of lithium metasilicate and
      cristobalite instead of lithium disilicate as major phase.

PMID- 21880356
TI  - Acne vulgaris.
AB  - Acne is a chronic inflammatory disease of the pilosebaceous unit resulting from
      androgen-induced increased sebum production, altered keratinisation,
      inflammation, and bacterial colonisation of hair follicles on the face, neck,
      chest, and back by Propionibacterium acnes. Although early colonisation with P
      acnes and family history might have important roles in the disease, exactly what
      triggers acne and how treatment affects the course of the disease remain unclear.
      Other factors such as diet have been implicated, but not proven. Facial scarring
      due to acne affects up to 20% of teenagers. Acne can persist into adulthood, with
      detrimental effects on self-esteem. There is no ideal treatment for acne,
      although a suitable regimen for reducing lesions can be found for most patients.
      Good quality evidence on comparative effectiveness of common topical and systemic
      acne therapies is scarce. Topical therapies including benzoyl peroxide,
      retinoids, and antibiotics when used in combination usually improve control of
      mild to moderate acne. Treatment with combined oral contraceptives can help women
      with acne. Patients with more severe inflammatory acne usually need oral
      antibiotics combined with topical benzoyl peroxide to decrease antibiotic
      resistant organisms. Oral isotretinoin is the most effective therapy and is used
      early in severe disease, although its use is limited by teratogenicity and other
      side-effects. Availability, adverse effects, and cost, limit the use of
      photodynamic therapy. New research is needed into the therapeutic comparative
      effectiveness and safety of the many products available, and to better understand
      the natural history, subtypes, and triggers of acne.

PMID- 21880357
TI  - Disturbance of benthic macrofauna in relation to hypoxia and organic enrichment
      in a eutrophic coastal bay.
AB  - This study demonstrated the spatiotemporal patterns of the environmental
      conditions and benthic macrofauna in Tokyo Bay, Japan, and investigated the
      factors causing disturbances in the assemblage structure. In the north-central
      areas, the density and species diversity of the macrobenthos was low. Although
      hypoxia appeared in July, defaunation occurred in August. The delayed defaunation
      and recolonization soon after the abatement of hypoxia were attributed to several
      polychaete and bivalve species that were tolerant to the hypoxic environment. In
      the southeastern areas, however, the density and species diversity of the
      macrobenthos was high throughout the year, and no defaunation was recorded.
      Multivariate analyses showed that the disturbance in the macrofauna correlated
      with organic enrichment in the sediment and bottom-water hypoxia. There is a
      concern about further impairment of the macrofauna in the bay due to the
      expansion of sediment with high levels of organic matter towards the southern
      regions that could cause hypoxia and subsequent defaunation.

PMID- 21880358
TI  - Trophic status of earthen ponds used for semi-intensive shrimp (Litopenaeus
      stylirostris, Stimpson, 1874) farming in New Caledonia (Pacific Ocean).
AB  - We have investigated temporal variability in the quantity and biochemical
      composition of sediment organic matter along with variables proxies of water
      eutrophication (e.g., inorganic nutrient and chlorophyll-a) at two shrimp farms
      located in the Southern coast of New Caledonia and characterised by clear
      differences in shrimp feeding practices and levels of initial trophic conditions.
      The results of our study reveal that the trophic status of the water column
      increased during the rearing cycle at both sites, determining a general, though
      moderated, eutrophication. However, the water column trophic descriptors did not
      allow to discriminate differences in the trophic status among the investigated
      sites or between sites in the same farming plant, even if they were subjected to
      different feeding practices and largely different initial characteristics of the
      sediment. Temporal variations in biopolymeric C and phytopigment sedimentary
      contents (used as proxies of benthic eutrophication) varied inconsistently among
      sites. The multivariate analyses did not identify significant temporal patterns
      in the benthic trophic status, but allowed discriminating the four investigated
      sites. The semi-intensive shrimp farming significantly contributed to changing
      the water column and sediments trophic status of the earthen ponds, but the
      extent of those changes was not consistently observed in all ponds. In any of the
      investigated ponds the trophic status exceeded concerning thresholds over which
      hypoxia or anoxia could occur. We conclude that the established semi-intensive
      practices adopted so far for shrimp farming activities in the earthen ponds of
      New Caledonia are able to maintain the status of the ponds below the
      eutrophication levels over which dystrophic crises could sharply abate most of
      the reared biomass.

PMID- 21880359
TI  - Enzymatic activities in spermatozoa and butyltin concentrations in Baltic turbot
      (Scophthalmus maximus).
AB  - Spermatozoal enzymes of fish (NAD+- and NADP-dependent dehydrogenases and
      creatine kinase (CK)) were previously determined to be sensitive to tributyltin
      (TBT) in laboratory experiments and were thus indicated for use as biomarkers for
      TBT exposure. However, the potential ability of spermatozoal enzymes as
      biomarkers of TBT exposure has never been recapitulated in a field study. For
      this purpose, the kinetic activities of spermatozoal enzymes of the natural
      turbot Scophthalmus maximus population from the Gulf of Gdansk (GDA) and the
      Pomeranian Bay (POM) in the southern Baltic Sea were measured. Gas
      chromatography/high-resolution mass spectrometry was used to determine the
      concentrations of TBT and its breakdown products, dibutyltin (DBT) and
      monobutyltin (MBT), in the muscle, liver and testes of the male turbot. Males
      from GDA had significantly higher enzymatic activities and butyltin (BT) content
      in tissues than those from POM. A general linear model (GLM) showed that lactate
      dehydrogenase (LDH), malate dehydrogenase (MDH), glucose-6-phosphate
      dehydrogenase (G6PDH) and CK activities increased significantly with BT
      concentration in the testes and liver. We indicate the potential effects of TBT
      pollution on the spermatozoal enzymes of Baltic turbot.

PMID- 21880360
TI  - Long-term impacts of coral bleaching events on the world's warmest reefs.
AB  - The southern Arabian Gulf houses some of the most thermally tolerant corals on
      earth, but severe bleaching in the late 1990s caused widespread mortality. More
      than a decade later, corals still dominated benthos (mean: 40 +/- 3% cover on 10
      sites spanning > 350 km; range: 11.0-65.6%), but coral communities varied
      spatially. Sites to the west generally had low species richness and coral cover
      (mean: 3.2 species per transect, 31% cover), with Porites dominated communities
      (88% of coral) that are distinct from more diverse and higher cover eastern sites
      (mean: 10.3 species per transect, 62% cover). These patterns reflect both the
      more extreme bleaching to the west in the late 1990s as well as the higher faviid
      dominated recruitment to the east in subsequent years. There has been limited
      recovery of the formerly dominant Acropora, which now represents <1% of the
      benthos, likely as a result of recruitment failure. Results indicate that severe
      bleaching can have substantial long-term impacts on coral communities, even in
      areas with corals tolerant to environmental extremes.

PMID- 21880361
TI  - Splitting and self-assembling of far-red fluorescent protein with an engineered
      beta strand peptide: application for alpha-synuclein imaging in mammalian cells.
AB  - We introduce the strategic development of self-assembling peptide/protein
      fragments based on the far-red fluorescent protein mPlum. The first beta strand
      (mPlum 1, 18 amino acids) of mPlum was engineered to spontaneously bind with the
      rest of the protein (mPlum 2-11, next 10 beta strands) and to form a native
      chromophore. The target beta strand mPlum 1 was separated from mPlum 2-11 and
      linked via a flexible peptide linker, resulting in fluorescently inactive
      circularly permuted mPlum protein (CpmPlum). In vitro evolution of this CpmPlum
      to a fluorescently active form and the subsequent splitting of the engineered
      mPlum 1 peptide afforded self-assembling mPlum fragments. Recombinantly expressed
      and synthetically prepared beta strand peptides were successfully assembled with
      the remaining mPlum protein in vitro and in cells. This developed pair of
      peptide/protein fragments was effectively used for peptide tag detection of alpha
      synuclein in mammalian cells. Sequential expression of self-assembling mPlum
      fragments offered an entirely genetically encoded sensing system of naturally
      unfolded alpha-synuclein.

PMID- 21880362
TI  - The development of collagen-GAG scaffold-membrane composites for tendon tissue
      engineering.
AB  - Current tissue engineering approaches for tendon defects require improved
      biomaterials to balance microstructural and mechanical design criteria. Collagen
      glycosaminoglycan (CG) scaffolds have shown considerable success as in vivo
      regenerative templates and in vitro constructs to study cell behavior. While
      these scaffolds possess many advantageous qualities, their mechanical properties
      are typically orders of magnitude lower than orthopedic tissues such as tendon.
      Taking inspiration from mechanically efficient core-shell composites in nature
      such as plant stems and porcupine quills, we have created core-shell CG
      composites that display high bioactivity and improved mechanical integrity. These
      composites feature integration of a low density, anisotropic CG scaffold core
      with a high density, CG membrane shell. CG membranes were fabricated via an
      evaporative process that allowed separate tuning of membrane thickness and
      elastic moduli and were found to be isotropic in-plane. The membranes were then
      integrated with an anisotropic CG scaffold core via freeze-drying and subsequent
      crosslinking. Increasing the relative thickness of the CG membrane shell was
      shown to increase composite tensile elastic modulus by as much as a factor of 36
      in a manner consistent with predictions from layered composites theory. CG
      scaffold-membrane composites were found to support tendon cell viability,
      proliferation, and metabolic activity in vitro, suggesting they maintain
      sufficient permeability while demonstrating improved mechanical strength. This
      work suggests an effective, biomimetic approach for balancing strength and
      bioactivity requirements of porous scaffolds for tissue engineering.

PMID- 21880363
TI  - Identification of a peptide that interacts with Nestin protein expressed in brain
      cancer stem cells.
AB  - Glioma stem cells (GSCs) are presumably major culprits for brain tumor
      initiation, progression, and recurrence after conventional therapies. Thus,
      selective targeting and eradication of GSCs may provide a promising and effective
      therapeutic approach. Here, we isolated a GSC-targeting (GSCT) peptide that
      demonstrated selective binding affinity for many undifferentiated GSCs using in
      vitro phage display technology. This GSCT peptide binds to isotypes of Nestin
      proteins specifically expressed in GSCs, enabling it to target Nestin-positive
      cells in human glioblastoma tissues. In human glioblastoma tissue specimens, the
      fluorescence-conjugated GSCT peptide could visualize putative GSC populations,
      showing its possible use as a diagnostic agent. GSCT peptide is also internalized
      into undifferentiated GSCs specifically in vitro, and moreover, intravenously
      injected GSCT peptide effectively penetrated into tissues, specifically
      accumulated in gliomas that arise from subcutaneous and orthotopic implantation,
      and predominantly targeted Nestin-positive cells in these tumors. Thus, our GSCT
      peptide may be useful for the development of more promising therapeutic and
      diagnostic modalities that target GSCs in brain tumors.

PMID- 21880364
TI  - Polymer encapsulated upconversion nanoparticle/iron oxide nanocomposites for
      multimodal imaging and magnetic targeted drug delivery.
AB  - Multimodal imaging and imaging-guided therapies have become a new trend in the
      current development of cancer theranostics. In this work, we encapsulate
      hydrophobic upconversion nanoparticles (UCNPs) together with iron oxide
      nanoparticles (IONPs) by using an amphiphilic block copolymer, poly (styrene
      block-allyl alcohol) (PS(16)-b-PAA(10)), via a microemulsion method, obtaining an
      UC-IO@Polymer multi-functional nanocomposite system. Fluorescent dye and anti
      cancer drug molecules can be further loaded inside the UC-IO@Polymer
      nanocomposite for additional functionalities. Utilizing the Squaraine (SQ) dye
      loaded nanocomposite (UC-IO@Polymer-SQ), triple-modal upconversion luminescence
      (UCL)/down-conversion fluorescence (FL)/magnetic resonance (MR) imaging is
      demonstrated in vitro and in vivo, and also applied for in vivo cancer cell
      tracking in mice. On the other hand, a chemotherapy drug, doxorubicin, is also
      loaded into the nanocomposite, forming an UC-IO@Polymer-DOX complex, which
      enables novel imaging-guided and magnetic targeted drug delivery. Our work
      provides a method to fabricate a nanocomposite system with highly integrated
      functionalities for multimodal biomedical imaging and cancer therapy.

PMID- 21880365
TI  - Bioimaging and toxicity assessments of near-infrared upconversion luminescent
      NaYF4:Yb,Tm nanocrystals.
AB  - In vitro or in vivo bioimaging utilizing the upconversion (UC) luminescence of
      rare earth fluoride nanocrystals (NCs) has attracted much attention, especially
      for Yb(3+)/Tm(3+) doped NCs with a near-infrared (NIR) UC emission at 800 nm.
      Herein, water-soluble NaYF(4):Yb,Tm NCs with strong NIR UC emission were
      synthesized with a solvothermal method. In vitro and in vivo bioimaging and
      toxicity assessments were carried out with HeLa cell and Caenorhabditis elegans
      (C. elegans) cases, respectively. NaYF(4):Yb,Tm NCs afforded an efficient NIR
      image of the HeLa cells with an incubation concentration of 10 MUg mL(-1), and
      CCK-8 assay revealed a low cytotoxicity. Fed with Escherichia coli (E. coli) and
      NCs together, the C. elegans showed a NIR image in the gut from the pharynx to
      the anus. Further, these NCs could be excreted out when those worms were then fed
      with only E. coli. Toxicity studies were further addressed with protein
      expression, life span, egg production, egg viability, and growth rate of the
      worms in comparison with those of the intact ones. The feeding of rare earth
      fluoride NCs with a dose of 100 MUg does not arise obvious toxicity effect from
      the growth to procreation. The in vitro and in vivo studies confirm that
      NaYF(4):Yb,Tm NCs could be served as an excellent NIR emission bioprobe with low
      toxicity.

PMID- 21880366
TI  - Galanin receptor-expressing dorsal horn neurons: role in nociception.
AB  - Galanin, along with enkephalins and neuropeptide Y, has been hypothesized to
      negatively modulate nociception in the superficial dorsal horn of the spinal
      cord. In the present study, we sought to determine the role of presumably
      excitatory dorsal horn galanin receptor-expressing neurons in nociception by
      selectively destroying GalR1-expressing superficial dorsal horn interneurons
      using lumbar intrathecal injections of the targeted cytotoxin, galanin-saporin
      (Gal-sap). Lumbar intrathecal injection of Gal-sap (500 ng) reduced
      immunoperoxidase staining for GalR1 in the superficial dorsal horn without
      affecting primary afferent neurons in lumbar dorsal root ganglia. Lumbar
      intrathecal Gal-sap also: 1--reduced nocifensive reflex responding on the thermal
      plate at 0.3  degrees C, 44  degrees C, and 47  degrees C; 2--increased hot side
      occupancy in a thermal preference task (15  degrees C vs 45  degrees C); and, 3-
      decreased escape from 44  degrees C and 47  degrees C, but not 20  degrees C.
      Thus, similar to lesions of mu opiate receptor-expressing dorsal horn
      interneurons, selective destruction of GalR1-expressing superficial dorsal horn
      neurons produces heat hypo-algesia, likely due to loss of GalR1-expressing
      excitatory interneurons leading to reduced activation of nociceptive projection
      neurons in response to aversive heat. These results are different than those seen
      with intrathecal neuropeptide Y-saporin and suggest the potential value of
      selectively targeting GalR1-expressing dorsal horn neurons to control pain.

PMID- 21880367
TI  - Validity of criteria-based content analysis (CBCA) at trial in free-narrative
      interviews.
AB  - OBJECTIVE: The reliability of child witness testimony in sexual abuse cases is
      often controversial, and few tools are available. Criteria-Based Content Analysis
      (CBCA) is a widely used instrument for evaluating psychological credibility in
      cases of suspected child sexual abuse. Only few studies have evaluated CBCA
      scores in children suspected of being sexually abused. We designed this study to
      investigate the reliability of CBCA in discriminating allegations of child sexual
      abuse during court hearings, by comparing CBCA results with the court's final,
      unappealable sentence. We then investigated whether CBCA scores correlated with
      age, and whether some criteria were better than others in distinguishing cases of
      confirmed and unconfirmed abuse. METHODS: From a pool of 487 child sexual abuse
      cases, confirmed and unconfirmed cases were selected using various criteria
      including child IQ>=70, agreement between the final trial outcome and the opinion
      of 3 experts, presence of at least 1 independent validating informative component
      in cases of confirmed abuse, and absence of suggestive questions during the
      child's testimonies. This screening yielded a study sample of 60 confirmed and 49
      unconfirmed cases. The 14 item version of CBCA was applied to child witness
      testimony by 2 expert raters. RESULTS: Of the 14 criteria tested, 12 achieved
      satisfactory inter-rater agreement (Maxwell's Random Error). Analyses of
      covariance, with case group (confirmed vs. unconfirmed) and gender as independent
      variables and age as a covariate, showed no main effect of gender. Analyses of
      the interaction showed that the simple effects of abuse were significant in both
      sex. Nine CBCA criteria were satisfied more often among confirmed than
      unconfirmed cases; seven criteria increased with age. CONCLUSION: CBCA scores
      distinguish between confirmed and unconfirmed cases. The criteria that
      distinguish best between the 2 groups are Quantity of Details, Interactions, and
      Subjective Experience. CBCA scores correlate positively with age, and
      independently from abuse; all the criteria test except 2 (Unusual Details and
      Misunderstood Details) increase with age. The agreement rate could be increased
      by merging criteria Unusual and Superfluous details that achieve a low inter
      rater agreement when investigated separately. PRACTICE IMPLICATION: Given its
      ability to distinguish between confirmed and unconfirmed cases of suspected child
      abuse, the CBCA could be a useful tool for expert opinion. Because our strict
      selection criteria make it difficult to generalize our results, further studies
      should investigate whether the CBCA is equally useful in the cases we excluded
      from our study (for example mental retardation).

PMID- 21880368
TI  - Genotoxicity and oxidative stress biomarkers in Carassius gibelio as endpoints
      for toxicity testing of Ukrainian polluted river waters.
AB  - This study aimed to assess oxidative stress and genotoxicity biomarkers in
      Prussian carp Carassius gibelio laboratory-exposed to water from polluted
      Ukrainian rivers in order to evaluate their usefulness as endpoints in a short
      term bioassay for toxicity testing of freshwaters. The micronucleus (MN) test and
      the frequency of cells with double nuclei (DN) in erythrocytes and gill cells
      were used as indicators of chromosome aberrations and abnormalities in cell
      divisions, respectively. Cellular antioxidant defenses i.e. antioxidant enzyme
      activities (catalase, Se-dependent glutathione peroxidase, total glutathione
      peroxidase and glutathione-S-transferase) and oxidative damage, i.e. lipid
      peroxidation (measured as thiobarbituric acid reactive substances) in the fish
      liver were used as biomarkers of oxidative stress. Exposure to the polluted river
      water samples for 96 h resulted in significantly increased MN and DN frequencies,
      limited increases in antioxidant enzyme activities and no changes in lipid
      peroxidation. Results suggest that MN and DN frequencies in C gibelio are useful
      endpoints in a short-term bioassay for genotoxicity testing of environmental
      water samples in contrast to the oxidative stress biomarkers applied that showed
      low potential for assessing sublethal effects after a 96 h exposure.

PMID- 21880369
TI  - An estrogen-responsive plasma protein expression signature in Atlantic cod (Gadus
      morhua) revealed by SELDI-TOF MS.
AB  - Compound-specific protein expression signatures (PESs) can be revealed by
      proteomic techniques. The SELDI-TOF MS approach is advantageous due to its
      simplicity and high-throughput capacity, however, there are concerns regarding
      the reproducibility of this method. The aim of this study was to define an
      estrogen-responsive PES in plasma of Atlantic cod (Gadus morhua) using the SELDI
      TOF MS technique. Protein expression analysis of male cod exposed to 17beta
      estradiol (E2) showed that 27 plasma peaks were differentially expressed
      following exposure. The reproducibility of this result was evaluated by
      reanalyzing the samples six months later, and a significant change in expression
      was confirmed for 13 of the 27 peaks detected in the first analysis. The
      performance of the reproducible E2-responsive PES, constituting these 13 peaks,
      was then tested on samples from juvenile cod exposed to 4-nonylphenol, North Sea
      oil, or North Sea oil spiked with alkylphenols. Principal component analysis
      revealed that nonylphenol-exposed cod could be separated from unexposed cod based
      on the E2-responsive PES, indicating that the PES can be used to assess
      estrogenic exposure of both juvenile and adult specimens of cod. A targeted
      antibody-assisted SELDI-TOF MS approach was carried out in an attempt to identify
      the E2-responsive peaks. Results indicated that 2 peaks were fragments of the
      well-known biomarkers VTG and/or ZRP. In this study, the SELDI-TOF MS technology
      has shown its potential for defining compound-specific PESs in fish.
      Nevertheless, thorough validation of reproducibility, specificity and sensitivity
      of a PES is required before it can be applied in environmental monitoring.

PMID- 21880370
TI  - Heroes for the past and present: a century of remembering Amundsen and Scott.
AB  - In 1911-1912 Roald Amundsen and Robert Falcon Scott led rival parties in a race
      to the geographic South Pole. While both parties reached the Pole--Amundsen first
      -Scott's men died on the return journey. Amundsen became a Norwegian icon through
      his record-setting travels; Scott became a symbol of courage and devotion to
      science. The memory of each was invoked at various points during the twentieth
      century in the context of contemporary Antarctic events. Scott's status as a
      scientific figure was central to the Scott Polar Research Institute, while
      Amundsen's lack of scientific legacy became a way for British polar explorers to
      differentiate themselves from Norwegian contemporaries during the interwar years.
      After 1945 Scott and Amundsen were again invoked as exemplars of national polar
      achievement, even as the rise of large-scale science on the continent
      overshadowed past British and Norwegian achievements. In the present Amundsen and
      Scott remain wedded to particular values, focused respectively on national
      achievement and sacrifice in the name of science, while their race has become
      secondary.

PMID- 21880371
TI  - Molecular cytogenetic interphase analysis of Phosphoinositide-specific
      Phospholipase C beta1 gene in paraffin-embedded brain samples of major depression
      patients.
AB  - Mood disorders represent a major medical need, as their chronic treatments are
      not effective in all patients. Literature data suggested that phosphoinositides
      (PI) signal transduction pathway and related molecules such as the
      Phosphoinositide-specific Phospholipase C (PI-PLC) enzymes, might be involved in
      the pathophysiology of mood disorders, including major depression. By using
      interphase fluorescent in situ hybridization methodology, we analyzed PLCB1 gene,
      which codifies for the PI-PLC beta1 enzyme, in paraffin embedded samples of
      orbito-frontal cortex of 15 patients affected with major depression and in 15
      normal controls. No deletions of PLCB1 were identified with the methodology used,
      which allows to exclude wide gene deletions. The results, the technical aspects
      of the FISH methodology, and its limitations are discussed.

PMID- 21880373
TI  - The load of short telomeres is increased and associated with lifetime number of
      depressive episodes in bipolar II disorder.
AB  - BACKGROUND: It has recently been hypothesized that bipolar disorders are
      associated with accelerated aging. Telomere dysfunction, a biomarker of aging, is
      determined by the load of short telomeres, rather than by the mean telomere
      length. To our knowledge, the load of short telomeres has not been reported in
      any psychiatric disorder. The aims of the study were to examine the load of short
      telomeres and the mean telomere length and their relationships with illness
      duration and lifetime number of depressive episodes in bipolar II disorder (BD
      II). METHODS: Twenty-eight patients (mean age=34.8 +/- 7.7) with a DSM-IV
      diagnosis of BD-II and 28 healthy control subjects (mean age=34.8 +/- 9.2)
      matched for age, sex, and education participated. The load of short telomeres
      (percentage of telomeres <3 kilobases) and mean telomere length in peripheral
      blood mononuclear cells were measured using high-throughput quantitative
      fluorescence in situ hybridization. RESULTS: The load of short telomeres was
      significantly increased in patients with BD-II relative to healthy controls and
      may represent 13 years of accelerated aging. The load of short telomeres and the
      mean telomere length were associated with lifetime number of depressive episodes,
      but not with illness duration. LIMITATIONS: Modest sample size and cross
      sectional design. CONCLUSIONS: Our results suggest that BD-II is associated with
      an increased load of short telomeres. Depressive episode-related stress may
      accelerate telomere shortening and aging. However, longitudinal studies are
      needed to fully clarify telomere shortening and its relationship with clinical
      variables in BD-II.

PMID- 21880372
TI  - The prevalence and clinical presentation of antenatal depression in rural South
      Africa.
AB  - BACKGROUND: Although the prevalence of depression is similar in pregnant,
      postpartum and non-pregnant women, the onset of new depression is higher during
      the perinatal period. Women of low-income, and those living in low and middle
      income countries, are known to be at particularly high risk. Early identification
      and treatment of antenatal depression may improve pregnancy outcomes and could
      serve as an early indicator of postnatal depression. Culturally sensitive and
      accurate diagnostic tools are urgently needed. METHODS: A consecutive series of
      109 pregnant women were recruited in the third trimester at a primary health
      clinic, in a rural part of South Africa, with a high HIV prevalence. A cross
      sectional assessment of depression was completed using a structured clinical
      interview method and DSM-IV diagnostic criteria. Qualitative data on women's
      descriptions of depressive symptoms was also collected. The aim was to examine
      the prevalence of depression and to better understand the presentation of
      depressive symptomatology in this population. RESULTS: Prevalence of depression
      was high, 51/109 (47%), with over half of the depressed women 34/51(67%)
      reporting episode duration greater than two months. 8/51 reported a prior history
      of depression. Women used psychological language to describe symptoms and, as a
      result, standardised diagnostic tools were culturally sensitive. Somatic
      pregnancy symptoms were frequently reported, but did not overestimate depression.
      Both HIV positive (27/51) and HIV negative (24/51) women were at risk of being
      depressed. LIMITATIONS: The study is limited by the small sample size and
      possible attrition biases. CONCLUSION: Antenatal depression is high and clinical
      presentation is similar to high income countries. Standardised diagnostic tools
      are culturally sensitive and adequate for early detection.

PMID- 21880374
TI  - Factors associated with presenteeism among employed Australian adults reporting
      lifetime major depression with 12-month symptoms.
AB  - BACKGROUND: Employees experiencing depression can take a sickness absence or
      continue working ('presenteeism'). However, little is known about the factors
      associated with these behaviors within this population. This study aimed to
      determine the relative importance of socio-demographic, financial, work and
      health-related factors associated with presenteeism. METHODS: The 2007 Australian
      National Survey of Mental Health and Wellbeing provided data from employed
      individuals reporting lifetime major depression with 12-month symptoms (N=320).
      Survey adjusted multivariable logistic regression assessed classification of 12
      month, depression-related presenteeism on the basis of socio-demographic,
      financial, work and health factors. RESULTS: Acceptable classification of cases
      was 70% or greater. Classification of cases based on socio-demographic factors,
      age, sex and marital status, was reasonable (62%). Adding work factors (work
      hours and occupation type) produced a 1% increase in successfully classified
      cases (63%). Health factors further increased correctly classified cases (67%).
      Marital status, housing tenure and co-morbid mental disorders were important
      indicators of presenteeism behavior. LIMITATIONS: Work-related variables were
      restricted to available measures. Potentially important psychosocial work
      environment factors were unavailable. Cross-sectional data precluded causal
      inference. CONCLUSIONS: Using available factors, model discrimination did not
      reach an acceptable level i.e. 70% of presenteeism cases successfully classified.
      This highlighted the contribution of unmeasured factors to presenteeism behavior.
      Future research should explore the relative importance of psychosocial work
      environment and personality factors such as work demands, effort/reward imbalance
      and conscientiousness. The identified associations between socio-demographic,
      financial and health factors on work attendance behaviors could inform disease
      management guidelines for employers via recognition of employees at risk of
      presenteeism.

PMID- 21880375
TI  - Low and dysregulated production of follistatin in immune cells of relapsing
      remitting multiple sclerosis patients.
AB  - One of the mechanisms known to play a key role in neuronal and oligodendroglial
      fate specification of neural stem cells (NSCs) is restriction of bone morphogenic
      proteins (BMP) signaling by BMP antagonists. Here, we demonstrate that
      follistatin mRNA and protein secreted levels in peripheral blood mononuclear
      cells (PBMCs) of relapsing-remitting multiple sclerosis (RR-MS) patients are
      significantly reduced compared to healthy controls (HC). We also observed a
      different profile of regulation mechanisms. Follistatin was similarly expressed
      and secreted by T lymphocytes and monocytes among the PBMCs of HC, and
      follistatin upregulation of HC was subjected to stimulation with both LPS and TNF
      alpha. Among PBMCs of RR-MS patients, however, follistatin was found to be
      downregulated in their monocytes and unresponsive to stimulation with either LPS
      or TNF-alpha. Our results may shed some light on the mechanisms involved in
      remyelination failure in MS, which may be related to the inability of RR-MS
      patients' immune cells to provide a sufficient pro-neurogenic and
      oligodendrogenic niche, by expressing and secreting follistatin, in addition to
      the previously described noggin reduced expression. Our results indicate that the
      low expression of follistatin in immune cells of patients with RR-MS is a result
      of the altered immunoregulation of monocytes in these patients.

PMID- 21880376
TI  - Foreign body reaction after cochlear implantation.
AB  - Cochlear implantation is a widely accepted, safe procedure for patients with
      severe to profound sensorineuronal hearing loss. While complications are rare,
      revision surgeries are required for complications like device failure, misplaced
      electrode, flap necrosis, and wound infection. Foreign body reaction is a rare
      complication following cochlear implantation. We experienced a case of foreign
      body reaction after cochlear implantation treated by device removal. Foreign body
      reaction has to be considered as one of several causes in cochlear implantation
      cases that show symptoms mimicking recurrent wound infection or delayed
      extrusion. We report a case of foreign body reaction with a literature review.

PMID- 21880377
TI  - Evolving treatments in the management of laryngotracheal hemangiomas: will
      propranolol supplant steroids and surgery?
AB  - There has been a dramatic evolution in the treatment of laryngotracheal
      hemangiomas during the past decade and recent accounts and case reports of
      propranolol treatment have been encouraging. The purpose of the study is to
      determine the clinical course and outcomes of treating laryngotracheal
      hemangiomas at The Children's Hospital of Philadelphia in the last 8 years with
      the various modalities. We review with contemporary surgical techniques,
      including propranolol, and determine the results, limitations and complications.
      The study was a retrospective review of all patients referred to the
      Otolaryngology service at The Children's Hospital of Philadelphia with
      symptomatic laryngotracheal hemangiomas between January 2002 and December 2010.
      The study consisted of 30 infants, ranging in age from 1 to 18 months at time of
      diagnosis. Surgical interventions included open surgical excision, laser surgery,
      microdebrider excision and/or propranolol therapy. The main outcome measures
      include improvement in symptoms, decannulation, number of required treatments and
      airway size. All but two patients underwent an initial trial of steroids.
      Thirteen patients underwent open surgical excision, 9 requiring cartilage grafts
      and 12 were done in a single stage. Twelve surgical patients remained
      asymptomatic. One patient with diffuse mediastinal disease experiencing
      postoperative airway symptoms despite a normal appearing airway improved on
      propranolol. Two patients underwent at least 2 laser ablations, 4 responded to
      systemic steroids alone, and 1 had microdebrider resection. In the last 14
      months, 12 patients have had propranolol therapy at a dose of 2mg/kg divided
      every 8h. Eight patients improved clinically within 1 week of initiating
      treatment. Four patients failed to respond to propranolol therapy; 1 patient
      subsequently underwent open excision and the other continued with a tracheostomy
      for 18 months and finally was decannulated. A third patient had a partial
      response, but remains relatively asymptomatic. A fourth patient has had no
      response at all. There were no major complications from propranolol; minor
      complications included diarrhea and decreased appetite. This study gives an
      overview of the evolution of hemangioma treatment at our institution over the
      last 8 years. Surgical excision remains an effective treatment for subglottic
      hemangiomas. Carefully administered, propranolol may demonstrate efficacy as a
      first-line agent in most cases avoiding surgery, tracheostomy, prolonged
      steroids, or as treatment of diffuse and unresectable disease. However, some
      lesions may be resistant to propranolol and require surgery or long-term
      steroids.

PMID- 21880379
TI  - Updating hippocampal representations: CA2 joins the circuit.
AB  - The hippocampus integrates the encoding, storage and recall of memories, binding
      the spatio-temporal and sensory information that constitutes experience and
      keeping episodes in their correct context. The rapid and accurate processing of
      such daunting volumes of continuously changing data relies on dynamically
      assigning different aspects of mnemonic processing to specialized, interconnected
      networks corresponding to the anatomical subfields of dentate gyrus (DG), CA3 and
      CA1. However, differentially processed information ultimately has to be
      reintegrated into conjunctive representations, and this is unlikely to be
      achieved by unidirectional, sequential steps through a DG-CA3-CA1 loop. In this
      Review, we highlight recently discovered anatomical and physiological features
      that are likely to necessitate updates to the hippocampal circuit diagram,
      particularly by incorporating the oft-neglected CA2 region.

PMID- 21880380
TI  - Sudden death related to tuberculous coronary arteritis.

PMID- 21880378
TI  - The renin-angiotensin-aldosterone system and glucose homeostasis.
AB  - The renin-angiotensin-aldosterone system (RAAS) is inappropriately activated in
      obesity. In individuals at risk for diabetes, RAAS inhibition protects against
      kidney and heart disease, and also reduces the incidence of diabetes in large
      clinical trials. At a cellular level, angiotensin II (Ang II) and aldosterone
      induce insulin resistance by increasing oxidative stress and altering insulin
      signaling, leading to decreased glucose transport. Ang II also contributes to
      oxidative stress, inflammation, and apoptosis in pancreatic beta cells.
      Aldosterone diminishes glucose-stimulated insulin secretion in vivo and in vitro
      from isolated pancreatic islets and cultured beta cells through a
      mineralocorticoid receptor (MR)-independent mechanism. We review these findings
      in the context of pharmacological strategies interrupting the RAAS to highlight
      the potential application of these strategies to the prevention of diabetes
      progression.

PMID- 21880381
TI  - Implantable loop recorders in myotonic dystrophy 1.

PMID- 21880382
TI  - Determinants of urban-rural differences in cardiovascular risk factors in middle
      aged women in India: a cross-sectional study.
AB  - OBJECTIVES: Cardiovascular diseases (CVD) are the most important cause of death
      amongst middle-aged Indian women. To determine prevalence of CVD risk factors and
      their determinants we performed a nationwide study. METHODS: Population based
      studies amongst women 35-70 years were performed in four urban and five rural
      locations in India. Location based stratified sampling was performed and we
      enrolled 4624 (rural 2616, urban 2008) of eligible 8000 women (58%). Demographic
      details, medical history, diet, physical activity and anthropometry were recorded
      using standardised techniques. Blood haemoglobin, glucose and total cholesterol
      were determined. Risk factors were diagnosed using current guidelines.
      Descriptive statistics are reported. Stepwise multivariate logistic regression
      was performed to identify determinants of urban-rural differences. RESULTS: In
      urban women mean body mass index (BMI), waist circumference, waist-hip ratio
      (WHR), systolic BP, haemoglobin, fasting glucose and cholesterol were
      significantly greater (p<0.01). Age-adjusted prevalence of risk factors (%) in
      urban vs rural was of obesity BMI >= 25 kg/m(2) (45.6 vs 22.5), truncal obesity
      WHR>0.9 (44.3 vs 13.0), hypertension (37.5 vs 29.3), hypercholesterolemia >= 200
      mg/dl (27.7 vs 13.5), and diabetes (15.1 vs 4.3) greater whilst any tobacco use
      (19.6 vs 41.6) or smoking lower. Significant determinants of urban-rural
      differences were greater income and literacy, dietary fats, low physical
      activity, obesity and truncal obesity (p<0.01). CONCLUSIONS: Greater prevalence
      of CVD risk factors in urban middle-aged women is explained by greater income and
      literacy, dietary fat, low physical activity and obesity.

PMID- 21880383
TI  - Effects of the Ala379Val polymorphism of lipoprotein-associated phospholipase A2
      on thrombosis and inflammation in hypertensive patients.

PMID- 21880384
TI  - Short-term deceleration capacity reveals higher reproducibility than spectral
      heart rate variability indices during self-monitoring at home.

PMID- 21880385
TI  - Treatment of recurrent vein graft "stent-in-stent" re-stenosis guided by optical
      coherence tomography.

PMID- 21880386
TI  - Impacts of a freedom farrowing pen design on sow behaviours and performance.
AB  - The limited space in farrowing crate imposes many challenges, such as prolonged
      farrowing duration and high piglet stillbirth rate. Although the features of
      farrowing pens compensate for the drawbacks of farrowing crates, they are
      associated with high piglet crushing mortality caused by the greater space
      afforded to sows and their rolling-over behaviour. Therefore, a freedom farrowing
      pen was designed to overcome the drawbacks of both farrowing crates and farrowing
      pens. The main features of the freedom farrowing pen are its left anti-crushing
      bar and detachable right anti-crushing bar on the sides of the sow lying area. It
      also has a 10 cm-high anti-crushing bar in the non-lying area. Eighteen healthy,
      multiparous Yorkshire sows (3-7 parity) were averaged and randomly assigned to
      farrowing crates, farrowing pens, and freedom farrowing pens to compare the
      effects of the farrowing systems on sow behaviour and performance. Results showed
      that the farrowing duration and the mean piglet birth intervals were longer for
      the sows in farrowing crates than for those in farrowing pens and freedom
      farrowing pens (P<0.05), but there was no difference between the sows in
      farrowing pens and those in freedom farrowing pens (P>0.05). The piglet
      stillbirth rate was higher for the sows in farrowing crates than for those in
      farrowing pens and freedom farrowing pens (P<0.001). Crushing mortality was
      higher among piglets in farrowing pens (P<0.001), but there was no difference
      between piglets in freedom farrowing pens and those in farrowing crates (P>0.05).
      The freedom farrowing pen and the farrowing pen allowed sows to turn around and
      move freely, but because of the different structures of their anti-crushing bars,
      the increase in sow movement did not cause higher piglet crushing mortality
      (P>0.05). Sows in freedom farrowing pens were found to be more protective of
      their piglets.

PMID- 21880387
TI  - Reirradiation of brain metastases with radiosurgery.
AB  - PURPOSE: To assess the outcome of reirradiation with stereotactic radiosurgery
      (SRS) of brain metastases (BM) recurring after whole brain radiotherapy (WBRT).
      METHODS AND MATERIALS: Between September 2001 and October 2008, 69 patients who
      recurred after WBRT were re-irradiated with SRS using a linear accelerator. The
      dose prescription was generally chosen according to maximum diameter of the tumor
      as suggested by Radiation Therapy Oncology Group (RTOG) 90-05 protocol. Patients
      were stratified by Karnofsky Performance Status (KPS), Neurologic Functional
      Score (NFS), RTOG Recursive Partitioning Analysis (RPA), Score Index for
      Radiosurgery (SIR), primary disease, dimension and number of BM, and time to
      first brain recurrence after WBRT. Response, survival, and toxicity were
      analyzed. RESULTS: At time of this retrospective analysis all patients had died.
      The 69 patients reirradiated with SRS had 150 metastases. Median interval between
      prior WBRT and SRS was 11 months and median SRS prescribed dose was 20 Gy.
      Response was obtained in 91% of lesions with 1-year local control rate of 74+/
      4%. Significantly longer duration of response was associated with higher doses
      (>=23 Gy) and response achieved after SRS (complete and partial response better
      than stable disease). Cause of death was brain failure only in 36 (52%) patients.
      Median overall survival after reirradiation was 10 months. Variables which
      significantly conditioned survival were KPS and NFS. Four (6%) patients had
      asymptomatic radionecrosis that developed prevalently when lesion diameters were
      larger and cumulative doses exceeded the values recommended by RTOG 90-05
      protocol. About three-fourth of the patients had a good KPS and NFS after
      reirradiation. CONCLUSIONS: Reirradiation of BM with SRS resulted feasible and
      effective. A correct patient selection and an accurate evaluation of the
      cumulative irradiation dose were suggested.

PMID- 21880388
TI  - Defining treatment conditions for pulsed electric field pasteurization of apple
      juice.
AB  - The influence of temperature and the presence of N(alpha)-lauroyl ethylester
      (ethyl lauroyl arginate, LAE) on the inactivation caused by continuous pulsed
      electric field treatments (PEF) in Escherichia coli O157:H7 suspended in apple
      juice have been investigated to define treatment conditions applicable at
      industrial scale that promote an equivalent safety level when compared with
      thermal processing. In the range of experimental conditions investigated (outlet
      temperature: 20-40  degrees C, electric field strength: 20-30 kV, treatment time:
      5-125 MUs) at outlet temperatures equal or lower than 55+/-1  degrees C, the
      inactivation of E. coli O157:H7 treated in apple juice ranged from 0.4 to 3.6
      Log10 cycles reduction and treated in apple juice supplemented with LAE (50 ppm)
      ranged from 0.9 to 6.7 Log10 cycles reduction. An empirical mathematical model
      was developed to estimate the treatment time and total specific energy input to
      obtain 5 Log10 cycles reduction in the population of E. coli O157:H7 suspended in
      apple juice supplemented with 50 ppm of LAE at different electric field strengths
      and inlet temperatures. Treatment conditions established for E. coli O157:H7 were
      validated with other PEF resistant Gram-positive (Listeria monocytogenes, and
      Staphylococcus aureus) and Gram-negative (Salmonella enterica serovar
      Typhimurium) strains. When the treatment was applied to the apple juice, a
      treatment of 25 kV/cm for 63 MUs corresponding with an outlet temperature of 65 
      degrees C and input energy of 125 kJ/kg was required to achieve more than 5 Log10
      cycles in the four strains investigated. The addition of LAE reduced the
      treatment time required to obtain an equivalent inactivation (>5 Log10 cycles) in
      the four microorganisms to 38.4 MUs, the outlet temperature to 55  degrees C, and
      the input energy to 83.2 kJ/kg.

PMID- 21880389
TI  - Effect of diagnosis-time and initial treatment on the onset of type 2 diabetes
      mellitus complications: a population-based representative cross-sectional study
      in Hungary.
AB  - We estimated the risk-increasing role of late-diagnosis on the onset of
      complications among 1168 patients representative of above 50 Hungarian diabetic
      population. Higher occurrence of retinopathy has been found in the late-diagnosis
      group (OR=1.62, 95% CI: 1.06-2.49). Clinically significant benefit of early
      diagnosis was not observable in case of other complications.

PMID- 21880390
TI  - A global overview of health insurance administrative costs: what are the reasons
      for variations found?
AB  - OBJECTIVES: Administrative costs are an important spending category in total
      health insurance expenditure. Yet, they have rarely been a topic outside the US
      and there is no cross-country comparison available. This paper provides a global
      overview and analysis of administrative costs for social security schemes (SSS)
      and private health insurance schemes (PHI). METHODS: The analysis is based on
      data of the World Health Organization (WHO) National Health Accounts (NHA) and
      the Organisation for Economic Cooperation and Development (OECD) System of Health
      Accounts (SHA). These are the only worldwide databases on health expenditure
      data. Further data was retrieved from a literature search. Administrative costs
      are presented as a share of total health insurance costs. RESULTS: Data is
      available for 58 countries. In high-income OECD countries, the average SSS
      administrative costs are 4.2%. Average PHI administrative costs are about three
      times higher. The shares are much higher for low- and middle-income countries.
      However, considerable variations across and within countries over time are
      revealed. DISCUSSION AND CONCLUSION: Seven explanatory factors are explored to
      explain the variations: health financing system aspects, administrative
      activities undertaken, insurance design aspects, context factors, reporting
      format, accounting methods, and management and administrative efficiency
      measures. More detailed reporting of administrative costs would enhance
      comparability and provide benchmarks. Improved administrative efficiency could
      free resources to expand coverage.

PMID- 21880391
TI  - Geometrical methods for level set based abdominal aortic aneurysm thrombus and
      outer wall 2D image segmentation.
AB  - Abdominal aortic aneurysm (AAA) is a localized dilatation of the aortic wall.
      Accurate measurements of its geometric characteristics are critical for a
      reliable estimate of AAA rupture risk. However, current imaging modalities do not
      provide sufficient contrast to distinguish thrombus from surrounding tissue thus
      making the task of segmentation quite challenging. The main objective of this
      paper is to address this problem and accurately extract the thrombus and outer
      wall boundaries from cross sections of a 3D AAA image data set (CTA). This is
      achieved by new geometrical methods applied to the boundary curves obtained by a
      Level Set Method (LSM). Such methods address the problem of leakage of a moving
      front into sectors of similar intensity and that of the presence of
      calcifications. The versatility of the methods is tested by creating artificial
      images which simulate the real cases. Segmentation quality is quantified by
      comparing the results with a manual segmentation of the slices of ten patient
      data sets. Sensitivity to the parameter settings and reproducibility are
      analyzed. This is the first work to our knowledge that utilizes the level set
      framework to extract both the thrombus and external AAA wall boundaries.

PMID- 21880392
TI  - Biased sampling: no 'Homer Simpson Effect' among high achievers.

PMID- 21880393
TI  - Intraguild mutualism.
AB  - Although studies of species linked by a common resource (i.e. ecological guilds)
      have so far mainly focused on competition and predation, guilds are also good
      places to find mutualism. In this review we consider some three- and four-species
      community modules to illustrate examples of wide relevance. Mutualism arises from
      various direct and indirect trophic and non-trophic interactions between species-
      and within modules both with and without intraguild predation. Species removal
      and augmentation experiments, other manipulations, direct measurements, and path
      analytic methods can determine the presence and intensity of mutualism within
      guilds. Such studies, particularly when associated with existing theory and new
      theoretical development, can help advance an interaction-based approach to
      community analysis that recognizes linkages among mutualism, predation and
      competition in natural systems.

PMID- 21880394
TI  - Adaptive monitoring in the real world: proof of concept.
AB  - We recently proposed the adaptive monitoring approach for improving ecological
      monitoring, but to date no explicit examples exist. In this review, we
      demonstrate adaptive monitoring using two new case studies where pre-existing
      monitoring programs were redesigned to address new policy and scientific
      questions without breaching the integrity of past and ongoing time-series data.
      Lessons underpinning successful adaptive monitoring are: better recognition of
      the potential inter-relationships between adaptive monitoring and adaptive
      management to improve adoption of both; an understanding of what constitutes
      adaptive monitoring so that it is readily differentiated from ad hoc and reactive
      monitoring; and the forging of partnerships between researchers, policy-makers
      and resource managers to accommodate differences between policy-relevant and
      research-relevant questions and differences in conceptual models of ecosystem
      function, structure and management.

PMID- 21880395
TI  - Photosynthesis, N(2) fixation and taproot reserves during the cutting regrowth
      cycle of alfalfa under elevated CO(2) and temperature.
AB  - Future climatic conditions, including rising atmospheric CO(2) and temperature
      may increase photosynthesis and, consequently, plant production. A larger
      knowledge of legume performance under the predicted growth conditions will be
      crucial for safeguarding crop management and extending the area under cultivation
      with these plants in the near future. N(2) fixation is a key process conditioning
      plant responsiveness to varying growth conditions. Moreover, it is likely to
      increase under future environments, due to the higher photosynthate availability,
      as a consequence of the higher growth rate under elevated CO(2). However, as
      described in the literature, photosynthesis performance is frequently down
      regulated (acclimated) under long-term exposure to CO(2), especially when
      affected by stressful temperature and water availability conditions. As growth
      responses to elevated CO(2) are dependent on sink-source status, it is generally
      accepted that down-regulation occurs in situations with insufficient plant C sink
      capacity. Alfalfa management involves the cutting of shoots, which alters the
      source-sink relationship and thus the photosynthetic behaviour. As the growth
      rate decreases at the end of the pre-cut vegetative growth period, nodulated
      alfalfa plants show photosynthetic down-regulation, but during regrowth following
      defoliation, acclimation to elevated CO(2) disappears. The shoot harvest also
      leads to a drop in mineral N uptake and C translocation to the roots, resulting
      in a reduction in N(2) fixation due to the dependence on photosynthate supply to
      support nodule function. Therefore, the production of new shoots during the first
      days following cutting requires the utilization of reduced C and N compounds that
      have been stored previously in reserve organs. The stored reserves are mediated
      by phytohormones such as methyl jasmonate and abscisic acid and in situations
      where water stress reduces shoot production this potentially enables the
      enhancement of taproot protein levels in nodulated alfalfa, which may lead to
      these plants being in better condition in the following cut/regrowth cycle.
      Furthering our knowledge of legume performance under predicted climate change
      conditions will be crucial for the development of varieties with better
      adaptation that will achieve greater and more efficient production values.
      Furthermore, for this purpose it will be necessary to improve existing
      methodologies and create new ones for phenotype characterization. Such knowledge
      will provide key information for future plant breeding programs.

PMID- 21880396
TI  - Hourly variability of cerebrospinal fluid biomarkers in Alzheimer's disease
      subjects and healthy older volunteers.
AB  - Large hour-to-hour variability has previously been demonstrated in the
      cerebrospinal fluid (CSF) concentrations of Alzheimer's disease (AD) biomarkers
      amyloid beta(42) (Abeta(42)) and Abeta(40) in healthy younger subjects. We
      investigated the within-subject variability over 36 hours in CSF Abeta and tau
      proteins, in older subjects and AD patients. Six patients with mild stage AD (59
      85 years, Mini Mental State Examination (MMSE) 16-26) and 6 healthy older
      volunteers (64-77 years) received an intrathecal catheter from which, during 36
      hours, each hour 6 mL of CSF was drawn. Concentrations of Abeta(42), Abeta(40),
      total tau, and phosphorylated tau were determined and the variability was
      analyzed. Within-subject variability within 3-hour periods was assessed as the
      coefficient of variation, which was comparable for these 4 biomarkers in controls
      (4.2%-4.6%) and AD (3.1%-5.8%). Variability over 12 hour periods was 5.3% to
      9.5%. These findings suggest that CSF biomarker variability is relatively low in
      healthy older controls and AD patients. Furthermore, continuous sampling of CSF
      proved to be a useful and robust method, which may also be used to investigate AD
      pathogenesis and to evaluate pharmacotherapeutic interventions.

PMID- 21880397
TI  - Amyloid neuropathology in the single Arctic APP transgenic model affects
      interconnected brain regions.
AB  - The Arctic APP mutation (E693G) within the amyloid beta (Abeta) domain of amyloid
      precursor protein (APP) leads to dementia with clinical features similar to
      Alzheimer's disease (AD), which is believed to be mediated via increased
      formation of protofibrils. We have generated a transgenic mouse model, TgAPParc,
      with neuron-specific expression of human amyloid precursor protein with the
      Arctic mutation (hAPParc), showing mild amyloid pathology with a relatively late
      onset. Here we performed a detailed analysis of the spatiotemporal progression of
      neuropathology in homozygous TgAPParc, focusing on intracellular Abeta and
      diffuse Abeta aggregates rather than amyloid plaques. We show that the
      neuropathology in homozygous TgAPParc mice starts with intracellular Abeta
      aggregates, which is followed by diffuse extracellular Abeta deposits in
      subiculum that later expands to brain regions receiving neuronal projections from
      regions already affected. Together this suggests that the pathology in TgAPParc
      mice affects interconnected brain regions and may represent a valuable tool to
      study the spread and progression of neuropathology in Alzheimer's disease.

PMID- 21880398
TI  - Synthesis and in vitro activity of novel N-3 acylated TSAO-T compounds against
      HIV-1 and HCV.
AB  - Preparation of a small library of derivatives of the potent HIV-1 Reverse
      Transcriptase inhibitor TSAO-T bearing mono or di-carbonyl substituents (designed
      after docking analysis) at position N-3 is reported. A one-pot synthetic
      methodology has been developed that involves: (i) mono-reaction of TSAO-T with
      glutaryl dichloride under phase transfer conditions and (ii) in situ acyclic
      substitution of the remaining chloro atom by oxygen or nitrogen nucleophiles. The
      method is compatible with the polyfunctionality of the TSAO-T molecule, proceeds
      with high conversion yields and allows introducing molecular diversity. The anti
      HIV-1 and -HCV activity was studied in cell culture. The new N-3 acylated TSAO-T
      derivatives are active against HIV-1 (nanomolar range). Anti-HCV activity was
      observed in the micromolar range, that is at compound concentrations that were
      found cytostatic against human T-lymphocytes.

PMID- 21880399
TI  - Biophysical and physicochemical methods differentiate highly ligand-efficient
      human D-amino acid oxidase inhibitors.
AB  - Many early drug research efforts are too reductionist thereby not delivering key
      parameters such as kinetics and thermodynamics of target-ligand binding. A set of
      human D-Amino Acid Oxidase (DAAO) inhibitors 1-6 was applied to demonstrate the
      impact of key biophysical techniques and physicochemical methods in the
      differentiation of chemical entities that cannot be adequately distinguished on
      the basis of their normalized potency (ligand efficiency) values. The resulting
      biophysical and physicochemical data were related to relevant pharmacodynamic and
      pharmacokinetic properties. Surface Plasmon Resonance data indicated prolonged
      target-ligand residence times for 5 and 6 as compared to 1-4, based on the
      observed k(off) values. The Isothermal Titration Calorimetry-derived
      thermodynamic binding profiles of 1-6 to the DAAO enzyme revealed favorable
      contributions of both DeltaH and DeltaS to their DeltaG values. Surprisingly, the
      thermodynamic binding profile of 3 elicited a substantially higher favorable
      contribution of DeltaH to DeltaG in comparison with the structurally closely
      related fused bicyclic acid 4. Molecular dynamics simulations and free energy
      calculations of 1, 3, and 4 led to novel insights into the thermodynamic
      properties of the binding process at an atomic level and in the different
      thermodynamic signatures of 3 and 4. The presented holistic approach is
      anticipated to facilitate the identification of compounds with best-in-class
      properties at an early research stage.

PMID- 21880400
TI  - Design, synthesis and docking studies of quinoline-oxazolidinone hybrid molecules
      and their antitubercular properties.
AB  - New series of quinoline-oxazolidinone hybrid molecules were synthesized based on
      the preliminary docking studies. All the newly synthesized compounds were
      characterized by spectral analyses. The newly synthesized compounds were screened
      for their antimycobacterial properties based on the promising preliminary
      antibacterial screening results. Amongst tested compounds, compounds 8a, 8j and
      13a were active at 0.65 MUg/mL against Mycobacterium tuberculosis H(37)Rv strain.
      The mode of action of these active compounds was carried out by docking of
      receptor enoyl-ACP reductase with newly synthesized candidate ligands 8a, 8j and
      13a. These compounds exhibited well established bonds with one or more amino
      acids in the receptor active pocket. From the docking studies, compound 8j was
      considered to be the best inhibitor.

PMID- 21880401
TI  - Estimating the costs associated with malnutrition in Dutch nursing homes.
AB  - BACKGROUNDS & AIMS: Malnutrition in western health care involves a tremendous
      burden of illness. In this study the economic implications of malnutrition in
      Dutch nursing homes are investigated as part of the Health and Economic Impact of
      Malnutrition in Europe Study from the European Nutrition for Health Alliance.
      METHODS: A questionnaire was developed, focussing on the additional time and
      resources spent to execute all relevant nutritional activities in nursing home
      patients with at risk of malnutrition or malnourished. Results were extrapolated
      on national level, based on the prevalence rates gathered within the national
      Prevalence Measurement of Care Problems 2009. RESULTS: The normal nutritional
      costs are 319 million Euro per year. The total additional costs of managing the
      problem of malnutrition in Dutch nursing homes involve 279 million Euro per year
      and are related to extra efforts in nutritional screening, monitoring and
      treatment. The extra costs for managing nursing home residents at risk of
      malnutrition are 8000 euro per patient and 10000 euro for malnourished patients.
      CONCLUSIONS: The extra costs related to malnutrition are a considerable burden
      for the nursing home sector and urge for preventive measures.

PMID- 21880402
TI  - Customisation of the decision support system MOIRA-PLUS for applications to the
      marine environment.
AB  - The present short communication describes a technique to customise the decision
      system MOIRA-PLUS for applications to the marine environment. MOIRA-PLUS was
      originally designed to predict the behaviour of 137Cs and 90Sr in fresh water
      ecosystems and to evaluate the environmental, social and economic impacts of
      selected countermeasures aimed at restoring the polluted environment and at
      reducing the doses to man. An example of application for predicting the
      concentration of radiocaesium of Chernobyl origin in the Mediterranean Sea is
      described and discussed. The technique allows the user to easily integrate
      existing state-of-the-art box models of sea water circulation into the MOIRA-PLUS
      decision system.

PMID- 21880403
TI  - Airborne radionuclides in mosses collected at different latitudes.
AB  - Terrestrial mosses are a promising medium for investigation and monitoring of
      airborne radionuclide depositions due to their widespread occurrence, ease of
      sampling, and the possibility of high-resolution gamma spectrometry measurements
      without preparatory chemical treatment of samples. The overall objective of the
      present study was to compare (7)Be, (210)Pb and (137)Cs activity concentrations
      (in Bq/kg) in moss samples collected at two different climate zones: the south of
      Thailand (7  degrees N) and in Serbia (~45  degrees N) in order to examine
      deposition of airborne radionuclide in these distant areas. Significant
      difference of the (210)Pb content (almost a factor of 2) in mosses was observed.
      The mean value of (7)Be activity in samples from Serbia was almost 40% higher
      than activity of those collected in Thailand. Level of (137)Cs in Thailand mosses
      was below the detection limit. It was shown that air transport of water droplets
      in the area of waterfalls and strong turbulence can deposit U and Th daughter
      nuclei.

PMID- 21880404
TI  - Qualitative comparison of curricula in oral and maxillofacial surgery training.
      Part 1: dental foundation training.
AB  - Dental foundation training (DFT) is a two-year programme being introduced for new
      dental graduates. It is not currently compulsory but there are plans to make it
      so. Those studying oral and maxillofacial surgery (OMFS) must complete both
      medical and dental degrees, and training, and if DFT becomes a requirement for
      dental registration, the process could be lengthened. We aimed to examine the
      overlap between DFT and medical foundation and core surgical training, to
      highlight areas of potential duplication for those who completed their surgical
      training before graduating from dental school. Relevant curricula for OMFS
      trainees were identified and compared with the DFT curriculum, and a qualitative
      assessment tool was developed to measure overlap between non-analogous curricula.
      Depending on previous experience, an OMFS trainee who completed core training in
      surgery before studying dentistry may already have covered 76% of the DFT
      curriculum. Areas with the least duplication in clinical skills (53%) were
      notably those related to restorative dentistry, prosthodontics, and
      periodontology, but there was considerable overlap in non-clinical areas such as
      communication skills (100%) and professionalism (90%). A method of standardised
      assessment of previous experience may allow for DFT to be shortened for OMFS
      trainees.

PMID- 21880405
TI  - Tumour recurrence after surgical removal of parotid pleomorphic salivary adenoma
      using a retrograde facial nerve dissection technique.
AB  - Recurrence after surgical removal of parotid pleomorphic salivary adenoma using
      retrograde facial nerve dissection is not well researched. We adopted retrograde
      nerve dissection for parotid surgery for benign disease as a standard procedure
      in 1995. The objective of this study was to establish the rate of recurrence of
      primary tumours associated with the technique after removal of parotid
      pleomorphic salivary adenoma. We recruited 59 patients over a 16-year (1995-2011)
      period and collected the data prospectively. Eight patients were excluded as they
      had died or had been lost to follow up. Male:female ratio was 16:35 and age range
      was 15-69 years. The mean tumour size as measured on magnetic resonance imaging
      (MRI) was 27.4mm. Thirty-eight patients had superficial parotidectomy, 8 had
      total parotidectomy, and 5 had partial superficial parotidectomy. Mean follow up
      from the date of operation was 104 months (median 98, range 17-171). All patients
      were reviewed and examined in 2011 to establish whether the tumour had recurred.
      One patient had developed a solitary nodular recurrence 8 years after the initial
      procedure. Recurrence was 2%. The rate of clinically apparent recurrence after
      parotidectomy for pleomorphic salivary adenoma in this study is low and is
      comparable with others reported.

PMID- 21880406
TI  - Preservation of the temporalis muscle during cranioplasty.

PMID- 21880407
TI  - The incidence of congenital anomalies associated with cleft palate/cleft lip and
      palate in neonates in the Konya region, Turkey.
AB  - Additional congenital anomalies have often been found in patients with orofacial
      clefts. We wanted to find out the incidence and type of congenital malformations
      that may accompany cleft palate (CP) and cleft lip and palate (CLP) in babies
      born in the Konya region. A total of 121 newborn babies with CP or CLP were
      prospectively included in the study, and all were assessed in detail for
      congenital anomalies. Of 121 babies, 86 (71%) had CLP and 35 (29%) had CP. There
      was at least one congenital malformation in 80 (66%) of the cases. Additional
      congenital malformations were seen in 26 (74%) of the 35 with isolated CP, and 54
      (63%) in the 86 patients with CLP (p<0.05). The most common congenital
      malformation was congenital heart disease, followed by head and neck anomalies.
      The most common congenital heart disease was atrial septal defect. A serious
      chromosomal anomaly was found in 18/121 patients with CP or CLP (15%). Of the 80
      babies in whom congenital malformations were found, 31 (39%) had dysmorphic
      features. While 21 (68%) of dysmorphic cases had isolated CP, 10 (32%) had CLP
      (p<0.05). The rates of premature delivery, intrauterine growth retardation, and
      consanguinity between parents were higher in patients with CP or CLP. The
      neonatal mortality was 20% (n=24). Our results indicate that at least one
      congenital anomaly is also present in about two-thirds of newborn babies with CP
      and CLP, and these anomalies significantly increase their morbidity and
      mortality. All newborn babies with CP and CLP should be screened for additional
      congenital anomalies, particularly of the cardiovascular system.

PMID- 21880408
TI  - "Everything that I thought that they would be, they weren't:" family systems as
      support and impediment to recovery.
AB  - Family help provision for adults diagnosed with co-occurring severe mental
      illness and substance dependence is understudied. This article draws on verbally
      administered structured and semi-structured interviews with one group of 122
      behavioral health care clients and one group of 54 client-nominated family
      members. In New Mexico, USA, these were collected as part of a larger, long-term
      study. We examine the latter's concerns and fears, relative desire to be involved
      with treatment, and difficulties connecting with professionals, as well as forms
      of assistance they gave to clients and intra-family communication. We found that
      family members' actions and communications often support client recovery through
      resource provision and other, intangible forms of help. However, their
      misunderstandings of and lack of knowledge about client experiences can also
      impede recovery. We also compare the two groups of interviewees' perspectives on
      assistance given to clients by family members. We give examples of family
      attempts to deliver help and their consequences. Last, we offer suggestions for
      providers and policymakers to better help family members achieve their goal of
      caring for clients in recovery.

PMID- 21880409
TI  - Influence of Valentine's Day and Halloween on birth timing.
AB  - It is known that cultural representations, in the form of stereotypes, can
      influence functional health. We predicted that the influence of cultural
      representations, in the form of salient holidays, would extend to birth timing.
      On Valentine's Day, which conveys positive symbolism, there was a 3.6% increase
      in spontaneous births and a 12.1% increase in cesarean births. Whereas, on
      Halloween, which conveys negative symbolism, there was a 5.3% decrease in
      spontaneous births and a 16.9% decrease in cesarean births. These effects reached
      significance at p < .0001, after adjusting for year and day of the week. The
      sample was based on birth-certificate information for all births in the United
      States within one week on either side of each holiday across 11 years. The
      Valentine's-Day window included 1,676,217 births and the Halloween window
      included 1,809,304 births. Our findings raise the possibility that pregnant women
      may be able to control the timing of spontaneous births, in contrast to the
      traditional assumption, and that scheduled births are also influenced by the
      cultural representations of the two holidays.

PMID- 21880410
TI  - Captured by motion: dance, action understanding, and social cognition.
AB  - In this review article, we summarize the main findings from empirical studies
      that used dance-related forms of rhythmical full body movement as a research tool
      for investigating action understanding and social cognition. This work has proven
      to be informative about behavioral and brain mechanisms that mediate links
      between perceptual and motor processes invoked during the observation and
      execution of spatially-temporally coordinated action and interpersonal
      interaction. The review focuses specifically on processes related to (a) motor
      experience and expertise, (b) learning and memory, (c) action, intention, and
      emotion understanding, and (d) audio-visual synchrony and timing. Consideration
      is given to the relationship between research on dance and more general embodied
      cognition accounts of action understanding and social cognition. Finally, open
      questions and issues concerning experimental design are discussed with a view to
      stimulating future research on social-cognitive aspects of dance.

PMID- 21880411
TI  - Developmental, cellular and molecular biology of benign prostatic hyperplasia.

PMID- 21880412
TI  - Open rivers: barrier removal planning and the restoration of free-flowing rivers.
AB  - Restoration of unobstructed, free-flowing sections of river can provide
      considerable environmental and ecological benefits. It removes impediments to
      aquatic species dispersal and improves flow, sediment and nutrient transport.
      This, in turn, can serve to improve environmental quality and abundance of native
      species, not only within the river channel itself, but also within adjacent
      riparian, floodplain and coastal areas. In support of this effort, a generic
      optimization model is presented in this paper for prioritizing the removal of
      problematic structures, which adversely affect aquatic species dispersal and
      river hydrology. Its purpose is to maximize, subject to a budget, the size of the
      single largest section of connected river unimpeded by artificial flow and
      dispersal barriers. The model is designed to improve, in a holistic way, the
      connectivity and environmental status of a river network. Furthermore, unlike
      most previous prioritization methods, it is particularly well suited to meet the
      needs of potamodromous fish species and other resident aquatic organisms, which
      regularly disperse among different parts of a river network. After presenting an
      initial mixed integer linear programming formulation of the model, more scalable
      reformulation and solution techniques are investigated for solving large,
      realistic-sized instances. Results from a case-study of the Pike River Watershed,
      located in northeast Wisconsin, USA, demonstrate the computational efficiency of
      the proposed model as well as highlight some general insights about systematic
      barrier removal planning.

PMID- 21880413
TI  - Isolated gait apraxia from an acute unilateral parasagittal lesion.

PMID- 21880414
TI  - 5-aza-2'-deoxycytidine enhances susceptibility of renal cell carcinoma to
      paclitaxel by decreasing LEF1/phospho-beta-catenin expression.
AB  - We investigated the molecular mechanisms by which 5-aza-2'-deoxycytidine (DAC)
      and paclitaxel (PTX) use lymphoid enhancer-binding factor 1 (LEF1) and the
      Wnt/beta-catenin pathway to synergistically interact against renal cell carcinoma
      (RCC). LEF1 expression was examined by real-time PCR and immunohistochemistry.
      The regulation of LEF1/beta-catenin protein expression by DAC and/or PTX was
      examined by Western blot and immunoprecipitation. To analyze the effect of LEF1
      on the proliferative ability of RCC cells and the synergy of DAC and PTX against
      RCC cells, an expression vector containing the full-length cDNA for LEF1 was
      transfected into RCC cells, and LEF1 expression was also decreased using siRNA
      technology. Our results confirmed that DAC and PTX synergistically decreased the
      expression of LEF1 in vivo and in vitro. Moreover, treatment of RCC cell lines
      with the combination of DAC and PTX caused a synergistic decrease in LEF1/phospho
      beta-catenin. Our study also demonstrated a negative correlation between LEF1
      expression and the proliferative ability of RCC cells. Although interfering with
      LEF1 expression did not abolish the synergy between the two agents, RCC cells
      expressing high levels of LEF1 displayed an increased synergistic effect compared
      with RCC cells expressing low levels of LEF1. This study suggests that LEF1 can
      enhance the proliferation of RCC cells and that the LEF1/beta-catenin complex
      plays an important role in the synergy of DAC and PTX against RCC cells.
      Moreover, the synergy between DAC and PTX may be more effective in RCC cells
      expressing high levels of LEF1.

PMID- 21880415
TI  - Reverse phase protein microarrays quantify and validate the bioenergetic
      signature as biomarker in colorectal cancer.
AB  - A reverse phase protein microarray approach has been applied to quantify proteins
      of energy metabolism in normal and tumor biopsies of colorectal cancer (CRC)
      patients. The metabolic proteome of CRC specimens revealed a profound shift
      towards and enhanced glycolytic phenotype and concurrent mitochondrial
      alteration. The metabolic signature discriminated CRC patients with highly
      significant differences in overall and disease-free prognosis. The quantification
      of the bioenergetic signature of the tumor offers a relevant biomarker of CRC
      that could contribute in the handling of these patients.

PMID- 21880416
TI  - Genotoxicity and biodegradation of quaternary ammonium salts in aquatic
      environments.
AB  - Biodegradation tests were conducted for three groups of quaternary ammonium salts
      (QAS) that differed in hydrophobic chain length or in hydrophilic properties. The
      degradation rate was influenced by the hydrocarbon chain length, the presence of
      aromatic or cyclic rings, and the occurrence of sulphur and oxygen atoms in the
      alkyl substituent. All tested QAS variants were biodegradable in an aquatic
      environment. The half life of the different QAS under these conditions ranged
      from 0.5 to 1.6 days and depended on the properties of the compound.
      Biodegradation intermediate products were identified by nuclear magnetic
      resonance spectrometry ((1)H NMR and (13)C NMR). Both the initial preparations
      and their biodegradation products were not genotoxic.

PMID- 21880417
TI  - Photocatalytic degradation of dimethoate using LbL fabricated TiO2/polymer hybrid
      films.
AB  - Degradation of dimethoate under UV irradiation using TiO(2)/polymer films
      prepared by the layer-by-layer (LbL) method was investigated. The thin films were
      fabricated on glass slides and the surface morphology and roughness of the thin
      films were characterized using X-ray diffraction (XRD), scanning electron
      microscopy (SEM) and atomic force microscopy (AFM). The effect of lamp intensity,
      catalyst loading in the layers, number of bilayers, pH and initial dimethoate
      concentration on the degradation of dimethoate was systematically studied. The
      degradation was monitored using high performance liquid chromatography (HPLC)
      analysis and total organic carbon (TOC) measurements as a function of irradiation
      time, to see the change in concentration of dimethoate and mineralization,
      respectively. Complete degradation of dimethoate was achieved under TiO(2)
      optimum loading of 4 g/L at an UV irradiation time of 180 min. Increase in the
      lamp intensity, catalyst loading and number of bilayers increased the rate of
      degradation. At a pH of 4.62, complete degradation of dimethoate was observed.
      The degradation efficiency decreased with increase in initial dimethoate
      concentration. The degradation byproducts were analyzed and confirmed by gas
      chromatography-mass spectra (GC-MS). Toxicity of the irradiated samples was
      measured using the luminescence of bacteria Vibrio fischeri after 30 min of
      incubation and the results showed more toxicity than the parent compound.
      Catalyst reusability studies revealed that the fabricated thin films could be
      repeatedly used for up to ten times without affecting the photocatalytic activity
      of the films. The findings of the present study are very useful for the treatment
      of wastewaters contaminated with pesticides.

PMID- 21880418
TI  - Biodegradation and detoxification of melanoidin from distillery effluent using an
      aerobic bacterial strain SAG5 of Alcaligenes faecalis.
AB  - Distillery effluent retains very dark brown color even after anaerobic treatment
      due to presence of various water soluble, recalcitrant and coloring compounds
      mainly melanoidins. In laboratory conditions, melanoidin decolorizing bacteria
      was isolated and optimized the cultural conditions at various incubation
      temperatures, pH, carbon sources, nitrogen sources and combined effect of both
      carbon and nitrogen sources. The optimum decolorization (72.6 +/- 0.56%) of
      melanoidins was achieved at pH 7.5 and temperature 37  degrees C on 5th day of
      cultivation. The toxicity evaluation with mung bean (Vigna radiata) revealed that
      the raw distillery effluent was environmentally highly toxic as compared to
      biologically treated distillery effluent, which indicated that the effluent after
      bacterial treatment is environmentally safe. This proves to be novel biological
      treatment technique for biodegradation and detoxification of melanoidin from
      distillery effluent using the bacterial strain SAG(5).

PMID- 21880419
TI  - Protective effect of Panax ginseng against serum biochemical changes and
      apoptosis in liver of rats treated with carbon tetrachloride (CCl4).
AB  - The purpose of this study was to investigate possible beneficial effects of Panax
      ginseng (PG) on carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in
      rats. CCl(4) challenge elevated serum enzyme activities of liver and some
      biochemical parameters, but these effects were prevented by the pretreatment of
      rats with PG. Histologically, a great amount of mononuclear cells infiltration,
      necrotic cells and few fibroblasts were observed in liver of CCl(4) group. Also,
      CD68(+) and caspase-3 staining cells were diffused in both lobular and portal
      areas. However, PG pretreatment had a little influence on the number of caspase-3
      immunopositive staining cells in the liver, but CD68(+) staining areas were
      significantly decreased in the PG+CCl(4) when compared to CCl(4) group. We
      conclude that PG treatment may play a protective role by enhancing liver enzyme
      activities and recovering biochemical parameters, and improving the changes in
      histological structure against CCl(4)-induced liver damages in rats.

PMID- 21880420
TI  - CFD simulation of pollutant dispersion around isolated buildings: on the role of
      convective and turbulent mass fluxes in the prediction accuracy.
AB  - Computational Fluid Dynamics (CFD) is increasingly used to predict wind flow and
      pollutant dispersion around buildings. The two most frequently used approaches
      are solving the Reynolds-averaged Navier-Stokes (RANS) equations and Large-Eddy
      Simulation (LES). In the present study, we compare the convective and turbulent
      mass fluxes predicted by these two approaches for two configurations of isolated
      buildings with distinctive features. We use this analysis to clarify the role of
      these two components of mass transport on the prediction accuracy of RANS and LES
      in terms of mean concentration. It is shown that the proper simulation of the
      convective fluxes is essential to predict an accurate concentration field. In
      addition, appropriate parameterization of the turbulent fluxes is needed with
      RANS models, while only the subgrid-scale effects are modeled with LES.
      Therefore, when the source is located outside of recirculation regions (case 1),
      both RANS and LES can provide accurate results. When the influence of the
      building is higher (case 2), RANS models predict erroneous convective fluxes and
      are largely outperformed by LES in terms of prediction accuracy of mean
      concentration. These conclusions suggest that the choice of the appropriate
      turbulence model depends on the configuration of the dispersion problem under
      study. It is also shown that for both cases LES predicts a counter-gradient
      mechanism of the streamwise turbulent mass transport, which is not reproduced by
      the gradient-diffusion hypothesis that is generally used with RANS models.

PMID- 21880421
TI  - Comments on the method of using maximum absorption wavelength to calculate Congo
      Red solution concentration published in J. Hazard. Mater.

PMID- 21880422
TI  - Alkali activated solidification/stabilisation of air pollution control residues
      and co-fired pulverised fuel ash.
AB  - This paper examines the potential treatment by solidification/stabilisation (S/S)
      of air pollution control (APC) residues using only waste materials otherwise
      bound for disposal, namely a pulverised fuel ash (PFA) from a co-fired power
      station and a waste caustic solution. The use of waste materials to stabilise
      hazardous wastes in order to meet waste acceptance criteria (WAC) would offer an
      economical and efficient method for reducing the environmental impact of the
      hazardous waste. The potential is examined against leach limits for chlorides,
      sulphates and total dissolved solids, and compressive strength performance
      described in the WAC for stable non-reactive (SNR) hazardous waste landfill cells
      in England and Wales. The work demonstrates some potential for the treatment,
      including suitable compressive strengths to meet regulatory limits. Monolithic
      leach results showed good encapsulation compared to previous work using a more
      traditional cement binder. However, consistent with previous work, SNR WAC for
      chlorides was not met, suggesting the need for a washing stage. The potential
      problems of using a non-EN450 PFA for S/S applications were also highlighted, as
      well as experimental results which demonstrate the effect of ionic interactions
      on the mobility of phases during regulatory leach testing.

PMID- 21880423
TI  - Inhibitory effects of Cu (II) on fermentative methane production using bamboo
      wastewater as substrate.
AB  - The toxic effects of Cu (II) present in bamboo industry wastewater (BIWW) upon
      its anaerobic biodegradability of organic content were investigated. The analysis
      through the Modified Gompertz model indicated that the optimum chemical oxygen
      demand (COD) concentration for digestion was 22,780 mg L(-1) with a maximum R(m)
      (maximum CH(4) production rate) value of 2.8 mL h(-1), corresponding to a
      specific methanogenic activity (SMA) of 2.38 mL CH(4) g VSS(-1)h(-1). The
      inhibitory effects of Cu (II) on cumulative methane production depended on its
      concentration and contact time. Low concentrations (5 mg L(-1)) of Cu (II) showed
      a stimulating effect on methanogenesis. Methane was not detected when the Cu (II)
      concentration was increased beyond 300 mg L(-1). The IC(50) value of Cu (II), the
      Cu (II) concentration that causes a 50% reduction in the cumulative methane
      production, was 18.32 mg L(-1) (15.9 mg Cu(II) gVSS(-1)).

PMID- 21880424
TI  - Anaerobic degradation of benzene by enriched consortia with humic acids as
      terminal electron acceptors.
AB  - The anaerobic degradation of benzene coupled to the reduction of humic acids (HA)
      was demonstrated in two enriched consortia. Both inocula were able to oxidize
      benzene under strict anaerobic conditions when the humic model compound,
      anthraquinone-2,6-disulfonate (AQDS), was supplied as terminal electron acceptor.
      An enrichment culture originated from a contaminated soil was also able to
      oxidize benzene linked to the reduction of highly purified soil humic acids
      (HPSHA). In HPSHA-amended cultures, 9.3 MUM of benzene were degraded, which
      corresponds to 279 +/- 27 micro-electron equivalents (MUEq)L(-1), linked to the
      reduction of 619 +/- 81 MUEq L(-1) of HPSHA. Neither anaerobic benzene oxidation
      nor reduction of HPSHA occurred in sterilized controls. Anaerobic benzene
      oxidation did not occur in soil incubations lacking HPSHA. Furthermore,
      negligible reduction of HPSHA occurred in the absence of benzene. The enrichment
      culture derived from this soil was dominated by two gamma-Proteobacteria
      phylotypes. A benzene-degrading AQDS-reducing enrichment originated from a
      sediment sample showed the prevalence of different species from classes beta-,
      delta- and gamma-Proteobacteria. The present study provides clear quantitative
      demonstration of anaerobic degradation of benzene coupled to the reduction of HA.

PMID- 21880425
TI  - Post-treatment of anaerobically degraded azo dye Acid Red 18 using aerobic moving
      bed biofilm process: enhanced removal of aromatic amines.
AB  - The application of aerobic moving bed biofilm process as post-treatment of
      anaerobically degraded azo dye Acid Red 18 was investigated in this study. The
      main objective of this work was to enhance removal of anaerobically formed the
      dye aromatic metabolites. Three separate sequential treatment systems were
      operated with different initial dye concentrations of 100, 500 and 1000 mg/L.
      Each treatment system consisted of an anaerobic sequencing batch reactor (An-SBR)
      followed by an aerobic moving bed sequencing batch biofilm reactor (MB-SBBR). Up
      to 98% of the dye decolorization and more than 80% of the COD removal occurred
      anaerobically. The obtained results suggested no significant difference in COD
      removal as well as the dye decolorization efficiency using three An-SBRs
      receiving different initial dye concentrations. Monitoring the dye metabolites
      through HPLC suggested that more than 80% of anaerobically formed 1-naphthylamine
      4-sulfonate was completely removed in the aerobic biofilm reactors. Based on COD
      analysis results, at least 65-72% of the dye total metabolites were mineralized
      during the applied treatment systems. According to the measured biofilm mass and
      also based on respiration-inhibition test results, increasing the initial dye
      concentration inhibited the growth and final mass of the attached-growth biofilm
      in MB-SBBRs.

PMID- 21880426
TI  - In situ neutralisation of uncarbonated bauxite residue mud by cross layer
      leaching with carbonated bauxite residue mud.
AB  - Unameliorated residue mud from the Bayer process generates highly alkaline
      leachates (pH ca. 13) after deposition in storage areas. Pre-deposition treatment
      of bauxite residue mud (BRM) with CO(2) gas (carbonation) lowers leachate pH to
      ca. 10.5. Laboratory scale leaching columns were used to investigate the
      potential for in situ pH reduction in existing uncarbonated BRM deposits through
      exposure to carbonated mud leachate. Leachates from uncarbonated and carbonated
      residues in single and dual-layer column configurations were analysed for pH,
      electrical conductivity, carbonate and bicarbonate content, and element
      concentrations. Air-dried solids were analysed by X-ray diffraction before and
      after leaching. Cross layer leaching lowers leachate pH from uncarbonated BRM.
      Leachate pH was significantly lower in dual layer and carbonated residue than in
      uncarbonated residue between one and 400 pore volumes leached. Carbonated residue
      porewater as well as dawsonite and calcite dissolution were identified as sources
      of (bi-)carbonate. Leachate concentrations of As, Cr, Cu, Ga and La were
      immediately reduced in dual layer treatments compared with uncarbonated residue.
      No element analysed exhibited a significantly higher leachate concentration in
      dual layer treatments than the highest observed concentration in single layer
      treatments. The implementation of dual layer leaching in the field therefore
      presents an opportunity to improve leachate quality from existing uncarbonated
      residue deposits and justifies further testing at field scale.

PMID- 21880427
TI  - Investigation of simultaneous adsorption of SO2 and NO on gamma-alumina at low
      temperature using DRIFTS.
AB  - The interaction mechanism between SO(2) and NO on gamma-Al(2)O(3) was explored by
      diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and outlet
      response of the concentrations of NO, NO(2) and SO(2) under exposure of Al(2)O(3)
      to SO(2) and/or NO in the absence or presence of oxygen at 150 degrees C. The
      results showed that SO(2) promoted NO oxidation and NO transformed weakly
      adsorbed SO(2) into strongly adsorbed species on gamma-Al(2)O(3), and the
      presence of O(2) facilitated this transformation. An interaction mechanism
      between SO(2) and NO on gamma-Al(2)O(3) was thus postulated. The exposure of
      Al(2)O(3) to SO(2) and NO in the presence of O(2) resulted in the formation of at
      least two types of intermediates. One type was [SO(3)NO], which decomposed to
      form NO(2), and the other type was [SO(3)NO(2)], which decomposed to form SO(3).
      The decomposition of both intermediates probably formed O vacancies replaceable
      by gaseous O(2).

PMID- 21880428
TI  - Science is not enough: the modern history of pediatric pain.

PMID- 21880429
TI  - Axenic culture and identification of amastigotes from Sichuan human strain of
      Chinese Leishmania isolates.
AB  - This work describes a simple method to yield large amounts of the isolate
      MHOM/CN/90/SC10H2 amastigotes-like forms in axenic cultures using promastigotes
      as the starting population. The isolate MHOM/CN/90/SC10H2, used in this study,
      belongs to an undescribed species of Leishmania endemic to hill foci in China.
      The method describes induced extracellular amastigote transformation of this
      isolate. The rounded parasite obtained in axenic culture was morphologically
      similar, even at the ultrastructural level, to intracellular amastigotes.
      Moreover, the axenic amastigotes remained viable as verified by the stage
      specific genes (gp46 and p4 genes) with RT-PCR. A 70-80 kDa protein was
      recognized by polyclonal antibody HRP-IgG only in axenic-derived amastigotes and
      not in promastigotes.

PMID- 21880430
TI  - Tactical treatment with copper oxide wire particles and symptomatic levamisole
      treatment using the FAMACHA((c)) system in indigenous goats in South Africa.
AB  - Haemonchosis is considered to be the most economically important gastrointestinal
      disease of small ruminants in the tropics and subtropics. However, chemical
      anthelmintics, which were the mainstay of control, have been compromised by a
      high prevalence of resistance worldwide. Copper oxide wire particles (COWP) have
      been shown to have anthelmintic effects, but few studies have examined their use
      under field conditions. The use of COWP was therefore evaluated as a tactical
      anthelmintic treatment in indigenous goats raised under communal farming
      conditions in Bergville, KwaZulu-Natal Province, South Africa. At the beginning
      of the summer rainfall season (October 2007), the faecal egg counts of 172 female
      goats belonging to 15 farmers were determined and this sampling continued every
      four weeks until the second week of January 2008. The goats within each of the 15
      herds were ranked according to their faecal egg counts for this week. The goats
      were sequentially paired off within each ranking starting with those goats with
      the highest counts. One goat from each pair was randomly allocated to a treated
      or control group. Two weeks later, a 4 g COWP bolus was randomly administered to
      each goat in the treated group. Faecal egg counts were carried out on the goats
      two weeks following treatment, and the sampling of the goats then proceeded every
      four weeks until October 2008. Except for the six-week period prior to the
      administration of the COWP, the goats were examined according to the FAMACHA((c))
      system and symptomatically treated with 12 mg/kg levamisole when anaemic. The
      percentage reduction in faecal egg count due to the COWP treatment was 89.0%.
      Mean pre- and post-treatment faecal egg counts for the COWP-treated group (n=73)
      were 2347 eggs per gram of faeces (epg) and 264 epg, respectively. The
      corresponding values for the untreated controls (n=66) were 2652 epg and 2709
      epg. The prevalence of Haemonchus spp. larvae in pre- and post-treatment faecal
      cultures was 72% and 46%, respectively. Symptomatic anthelmintic treatments in
      combination with mid-summer tactical treatments with COWP appear to be useful
      strategies for the control of Haemonchus contortus in indigenous goats in this
      farming system and this approach could have application in other similar agro
      ecological zones.

PMID- 21880431
TI  - Treatment use and barriers among adolescents with prescription opioid use
      disorders.
AB  - BACKGROUND: This study examined national trends, patterns, correlates, and
      barriers to substance abuse treatment use by adolescents aged 12-17 years who met
      at least one of the past-year criteria for prescription opioid abuse or
      dependence (N=1788). METHODS: Data were from the 2005-2008 National Surveys of
      Drug Use and Health (NSDUH). Past-year substance use disorders, major depression,
      and treatment use were assessed by audio computer-assisted self-interviewing.
      RESULTS: About 17% of adolescents with opioid dependence (n=434) and 16% of those
      with opioid abuse (n=355) used any substance abuse treatment in the past year
      compared with 9% of subthreshold users, i.e., adolescents who reported 1-2
      prescription opioid dependence criteria but no abuse criteria (n=999). Only 4.2%
      of adolescents with opioid dependence, 0.5% of those with abuse, and 0.6% of
      subthreshold users reported a perceived need for treatment of nonmedical opioid
      use. Self-help groups and outpatient rehabilitation were the most commonly used
      sources of treatment. Few black adolescents used treatment (medical settings,
      3.3%; self-help groups, 1.7%) or reported a need for treatment (1.8%). Talking to
      parents/guardians about dangers of substance use increased the odds of treatment
      use. Barriers to treatment use included "wasn't ready to stop substance use,"
      "didn't want others to find out," and "could handle the problem without
      treatment." CONCLUSIONS: Adolescents with prescription opioid use disorders
      markedly underutilize treatment. Non-financial barriers are pervasive, including
      stigma and a lack of perceived treatment need.

PMID- 21880432
TI  - Pain response in heroin users: personality, abstinence, and modulation by
      benzodiazepines.
AB  - We compared cold-pain responses among male current opioid users with and without
      concurrent benzodiazepine use, long-term ex-users, and healthy controls. Forty
      eight current opioid users (14 concurrently using benzodiazepines), 34 ex-users
      (abstinent for >=1 y) and 63 controls received cold-pressor tests. Pain threshold
      (first reporting pain) and pain tolerance (total immersion time) were recorded.
      Pain thresholds were similar in ex-users and current users; pain tolerance was
      similar in ex-users and controls. Net pain tolerance (endurance) in ex-users was
      intermediate between the other two groups. Current users showed higher pain
      threshold and shorter pain tolerance than controls (p<0.05). Current users not co
      using benzodiazepines showed the lowest pain tolerance and net pain tolerance,
      and differed significantly from controls, ex-users, and current users co-using
      benzodiazepines (p<0.05). Neuroticism was higher in current users than in the
      other two groups (p<0.001), extraversion marginally lower (p<0.05); net pain
      tolerance differences remained significant after controlling for these.
      Benzodiazepine use modulates pain tolerance in opioid users. Pain responses
      altered by opioid use may partially recover with abstinence.

PMID- 21880433
TI  - Parental involvement protects against self-medication behaviors during the high
      school transition.
AB  - We examined how drinking patterns change as adolescents transition to high
      school, particularly as a function of parental involvement. Stress associated
      with the transition to high school may deplete psychological resources for coping
      with negative daily emotions in an environment when opportunities to drink are
      more common. A cohort of elevated-risk middle school students completed daily
      negative affect (sadness, worry, anger, and stress) and alcohol use assessments
      before and after the transition to high school, resulting in a measurement burst
      design. Adolescents who reported less parental involvement were at higher risk
      for drinking on any given day. After (but not before) the transition to high
      school, daily within-person fluctuations of sadness predicted an increased
      probability of same-day alcohol use for adolescents who reported that their
      parents were minimally involved in their lives. The other negative affect
      indicators were not predictive of use. Our results suggest that the transition to
      high school may represent an important intervention leverage point, particularly
      for adolescents who lack adequate parental support to help them cope with day-to
      day changes in sadness.

PMID- 21880434
TI  - Advanced glycation end products overload might explain intracellular cobalamin
      deficiency in renal dysfunction, diabetes and aging.
AB  - Advanced glycation end products (AGEs) contribute to aging. Cobalamin (Cbl) is
      required for cell growth and functions, and its deficiency causes serious
      complications. Diabetics and renal patients show high concentrations of Cbl, but
      metabolic evidence of Cbl deficiency that is reversible after Cbl treatment. Cbl
      might be sequestered in blood and cannot be delivered to the cell. Megalin
      mediates the uptake of transcobalamin-Cbl complex into the proximal tubule cells.
      Megalin is involved in the uptake and degradation of AGEs. In aging, diabetes or
      renal dysfunction, AGEs might overload megalin thus lowering Cbl uptake.
      Transcobalamin-Cbl might retain in blood. Shedding of megalin and transcobalamin
      receptor under glycation conditions is also a possible mechanism of this
      phenomenon.

PMID- 21880435
TI  - Why not "double schizophrenia"?
AB  - The current approach to schizophrenic psychoses comprises the concept of a course
      characterized by a prodromal phase, an intermittent acute phase, and residual
      formation. Similar to the concept of the so-called double depression, there are,
      in addition to the subgroups of patients with primarily cognitive changes,
      patients in whom neurotic-dissociative components dominate prior to the disease
      outbreak itself. The question arises whether this process, considered thus far as
      prodromal, may possibly be interpreted beyond this as a combined pattern of
      progression in the sense of a "double schizophrenia" and thus differ
      symptomatically in the further course from other forms of schizophrenia. If so,
      in addition to the usual neuroleptic treatment, therapy should include an
      additional focus with more psychotherapeutic attention.

PMID- 21880436
TI  - Assessment of the angiotensin-I-converting enzyme (ACE-I) inhibitory and
      antioxidant activities of hydrolysates of bovine brisket sarcoplasmic proteins
      produced by papain and characterisation of associated bioactive peptidic
      fractions.
AB  - The main objective was to investigate the angiotensin-I-converting enzyme (ACE-I)
      inhibitory and antioxidant activities of sarcoplasmic proteins isolated from the
      brisket muscle (Pectoralis profundus) of 3 (Bos taurus) cattle and hydrolysed
      with papain for 24 h at 37 degrees C. Sarcoplasmic protein hydrolysates were
      ultra-filtered using molecular weight cut off (MWCO) membranes and 10-kDa and 3
      kDa filtrates were obtained. The total sarcoplasmic protein extracts and the 3
      kDa filtrates were tested for angiotensin I-converting enzyme inhibitory (ACE-I)
      activities. The total hydrolysates, 10-kDa and 3-kDa filtrates were also tested
      for their associated antioxidant activities using the 2,2-diphenyl-1
      picrylhydrazyl (DPPH) radical scavenging activity assay, the ferric ion reducing
      antioxidant power (FRAP) assay and the Fe(2+) metal chelating ability assay. The
      peptidic content of the total hydrolysates, the 10-kDa and the 3-kDa filtrates
      were analysed using an ORBITRAP mass spectrometer, and mass spectral data
      obtained were analysed using TurboSEQUEST. Eleven peptides were characterised
      from the total hydrolysates, fifteen from the 10-kDa filtrate fractions, whilst
      nine peptides were characterised from the 3-kDa filtrate fractions. Similarities
      between the amino acid sequences of the peptides identified in this study and
      previously identified antioxidant and ACE-I inhibitory peptides detailed in the
      BIOPEP database were outlined.

PMID- 21880437
TI  - [Use of Monica AN24TM for fetal monitoring during labour induction].

PMID- 21880438
TI  - [Prenatal management of a fetal pericardial teratoma with pericardio-amniotic
      shunting: a case report].
AB  - Fetal intrapericardial teratomas are uncommon and usually benign. Their histology
      is the same as that of teratomas located elsewhere. They may cause death from non
      immune hydrops fetalis and cardiac tamponade. We report a case that was
      successfully managed prenatally by placement of a pericardial amniotic shunt.

PMID- 21880439
TI  - [Fetal atrioventricular interval measurement: technical aspects].
AB  - Atrioventricular (AV) interval measurement allows early diagnosis of isolated
      congenital heart block linked to maternal antibodies anti-Ro/SSA and/or anti
      La/SSB. Simple and reliable ultrasound techniques have been developed to assess
      AV interval but most of them are imperfectly implemented by sonographers. In
      threatening conditions fetus should be regularly screened between 16 to 30 weeks.
      Increased AV interval defines the first degree AV block which should be treated
      by maternal-fetal corticosteroid to prevent complete heart block occurrence. The
      most recent ultrasound methods are based on pulsed Doppler rather than time
      motion Doppler. We describe the most important technical aspects to improve the
      evaluation of the fetal AV interval.

PMID- 21880440
TI  - Expression of androgen receptor and estrogen receptor-alpha in the developing
      pituitary gland of male sheep lamb.
AB  - To explore the expression of androgen receptor (AR) and estrogen receptor alpha
      (ERalpha) in the developing pituitary of male lamb, we detected AR and ERalpha
      expression in the anterior pituitary of lambs aged 2-7 months old by
      immunohistochemistry. The results showed that both AR immunoreactivity (AR-ir)
      and ERalpha immunoreactivity (ERalpha-ir) were localized in the nuclei of
      anterior pituitary cell. The percentage of the anterior pituitary cells
      expressing ERalpha fluctuated from 8.79+/-0.02% to 11.80+/-0.04% during the
      examined stages, but fell significantly to the lowest level at 6 months. While
      the proportion of AR-ir showed significant changes, it was in 11.52+/-1.26% at 2
      months, it firstly increased to 19.86+/-1.03% at 3 months, and then significantly
      decreased to 8.18+/-1.17% at 6 months (P<0.05). The expression of both AR-ir and
      ERalpha-ir were the lowest level at 6 months old. By staining for PCNA, we
      observed that the changes in expression of AR and ERalpha at different lamb ages
      did not result from cell proliferation of anterior pituitary cells. These results
      indicate that both AR and ERalpha are important in regulation of secretary
      function of anterior pituitary in sheep lamb, although the related mechanism
      needs to be elucidated further.

PMID- 21880441
TI  - Improved physical function and physical activity in older adults following a
      community-based intervention: Relationships with a history of depression.
AB  - The purpose of this study was to explore the relationship of a history of
      depression with moderate physical activity and physical function before and after
      a physical activity intervention of congregate meal participants in senior
      centers from all 12 Georgia Area Agencies on Aging (AAA). Participants were a
      convenience sample of older adults (n=376, mean age=76 years, 82% female, 64%
      Caucasian, 36% African American, 22% a history of depression). The physical
      activity intervention included educator-led chair exercises that incorporated
      balls and bands. Pre- and post-tests assessed moderate physical activity and
      physical function. At the pre-test, a history of depression was not related to
      moderate physical activity or physical function. Following the intervention there
      were significant increases in both moderate physical activity and physical
      function, but a history of depression was a negative predictor of improvements in
      physical activity when controlled for site, demographics, and health-related
      conditions. These results provide an evidence base for the effectiveness of this
      intervention in improving moderate physical activity and physical function in a
      community setting, but additional efforts may be needed to improve the impact of
      this type of intervention among older adults with a history of depression.

PMID- 21880442
TI  - In vitro production of GHB in blood and serum samples under various storage
      conditions.
AB  - The in vitro production of GHB was observed in freshly collected, untreated whole
      blood samples using glass BD-Vacutainers and polypropylene S-monovettes. GHB
      concentrations were determined daily over a period of one week and after 3, 6 and
      9 weeks again. Furthermore, the GHB concentration in 40 untreated random whole
      blood samples stored at 4 degrees C for a longer period of time (10 samples 12
      month, 10 samples 24 month and 20 samples 36 month) was also determined. For
      comparison, the in vitro production of GHB in freshly collected and prepared
      serum samples was observed. GHB serum concentrations were determined three times
      over a period of one week and once again after six weeks. Sample preparation was
      performed by means of methanolic extraction following the precipitation of whole
      blood and serum samples. A methanolic standard calibration was done in a low
      range of 0.005-0.1 MUg/mL (LOD: 0.004, LLOQ: 0.013). For quantification a spiked
      blood bank serum with a determined GHB concentration of 0.09 MUg/mL was used.
      Corrected calibrations in the range of 0.09-5.09 MUg/mL were used (LOD: 0.08
      MUg/mL, LLOQ: 0.30 MUg/mL), recovery: 91.3% (high level: 4.09 MUg/mL) 50.5% (low
      level: 0.19 MUg/mL). RESULTS: Relevant elevation of GHB was observed in all whole
      blood samples stored in liquid form (4 degrees C or room temperature). In two of
      the 40 whole blood samples stored over a longer period of time at 4 degrees C,
      GHB concentrations in the range of 13 MUg/mL were even determined. These findings
      constitute grounds for caution. Even a GHB cut-off level of 5 MUg/mL cannot be
      considered as "absolutely positive" proof of a case of exogenous administration,
      at least in untreated liquid blood samples in long time storage. However, no
      significant elevations of GHB were otherwise observed in any of the serum samples
      independently of storage temperature nor in the whole blood samples that were
      frozen for storage. CONCLUSIONS: The results suggest that the cut-off for
      exogenous GHB of 5 MUg/mL could be lowered significantly, with the consequence of
      winning valuable time for the potential victim, but only if serum is collected
      for GHB determination or if the whole blood sample is frozen immediately after
      collection and the procedure well documented.

PMID- 21880443
TI  - Evaluation of pediatric skull fracture imaging techniques.
AB  - Radiologic imaging is crucial in the diagnosis of skull fracture, but there is
      some doubt as to whether different imaging modalities can accurately identify
      fractures present on a human skull. While studies have been performed to evaluate
      the efficacy of radiologic imaging at other anatomical locations, there have been
      no systematic studies comparing various CT techniques, including high resolution
      imaging with and without 3D reconstructions to conventional radiologic imaging in
      children, we investigated which imaging modalities: high-resolution CT scan with
      3D projections, clinical-resolution CT scans or X-rays, best showed fracture
      occurrence in a pediatric human cadaver skull by having an expert pediatric
      radiologist examine radiologic images from fractured skulls. The skulls used were
      taken from pediatric cadavers ranging in age from 5 months to 16 years. We
      evaluated the sensitivity and specificity for the imaging modalities using
      dissection findings as the gold standard. We found that high-resolution CT scans
      with 3D projections and conventional CT provided the most accurate fracture
      diagnosis (single-fracture sensitivity of 71%) followed by X-rays (single
      fracture sensitivity of 63%). Linear fractures outsider the region of the sutures
      were more identifiable than diastatic fractures, though the incidence of false
      positives was greater for linear fractures. In the two cases where multiple
      fractures were present on the same anatomical skull location, the radiologist was
      less likely to identify the presence of additional fractures than a single
      fracture. Overall, the high-resolution and clinical-resolution CT scans had the
      similar accuracy for detecting skull fractures while the use of the X-ray was
      both less accurate and had a lower specificity.

PMID- 21880444
TI  - Child sexual abuse.
AB  - OBJECTIVE: To evaluate the prevalence of sexual abuse in the pediatric population
      of the Federal District and discuss the difficulties in interpreting the
      examination of the genitalia in this age group, both by general practitioners as
      medical expert forensic officers. METHODOLOGY: This is a retrospective,
      transversal, and epidemiological study on children younger than 12 years, who
      attended the Institute of Forensic Medicine of DF (IML-DF), Brasilia, Brazil,
      with suspicion of sexual abuse between 2008 and 2009. RESULTS: During this
      period, 3607 persons with suspected sexual abuse and 1762 (48.8%) children
      younger than 12 years were treated in IML-DF. Of this total, 238 (13.5%) were
      boys, and 1524 (86.5%) were girls. Among the boys, the average age was 6.5 years,
      and 9.6% were found to have injuries consistent with sexual abuse. In 43.4% of
      these cases, the perpetrator was known. The main lesions found were anal fissures
      and lacerations, bruises, and anal dilatation. In 20 cases (8.4%), the time
      interval between fact and examination precluded any conclusion. The girls (1524
      cases) referred to the IML-DF were subjected to two types of tests: libidinous
      acts (773 to 50.7%) and rape (751 to 49.3%). In tests of libidinous acts, 5.3%
      had signs of sexual abuse perpetrated by acquaintances (68.2%), and 3.0% were
      inconclusive because of the long time lag between the examination and fact. In
      survey of rape cases, only 2.1% of subjects examined had lesions consistent with
      abuse. In 57 of 1524 cases, specimens were sampled for sperm test, and five cases
      (8.7%) showed positive results. The average age of girls being sexually abused
      (10.7 years) was higher than that for boys (6.5 years). DISCUSSION: Our findings
      confirm the discrepancy between the expectations of parents and the general
      practitioner, and the reality of the findings in specialized centers.
      Approximately 90% of child victims of abuse do not show evidence of physical
      damage. These were found in less than 10% of abused children. Physical signs of
      abuse often are difficult to recognize and should not be the only indicators.

PMID- 21880445
TI  - Malignant paroxysmal positional vertigo.
AB  - OBJECTIVE: An insidious percentage of paroxysmal positional vertigo appears to be
      intractable with canalith repositioning maneuver and also is not self-limiting.
      This type of positional vertigo is sustained by the action of intracranial tumors
      that mimics the clinical aspects of benign paroxysmal positional vertigo.Aim of
      this study is to clarify the features of these forms of positional vertigo, which
      we indicate as malignant paroxysmal positional vertigo. METHODS: We
      retrospectively reviewed the clinical records of all the patients who presented
      with vertigo spells and were managed at our tertiary care referral centre over a
      three years period. Two hundred and eleven patients with diagnosis of positional
      paroxysmal vertigo were included in the final study. RESULTS: Seven patients were
      affected by intracranial tumors causing a positional vertigo and were classified
      as malignant paroxysmal positional vertigo patients after radiological and
      histological diagnosis. These patients were affected by an internal auditory
      canal mass alone or with extension in the cerebello pontine angle that mimicked a
      benign positional vertigo. CONCLUSION: We can conclude that the clinician should
      keep in mind the differentiation between benign positional vertigo and malignant
      positional vertigo. When the patients with positional vertigo presents a strange
      behaviour of symptoms, nystagmus or response to the canalith repositioning
      maneuver a radiological investigation must be undertaken in every doubtful case.

PMID- 21880446
TI  - Brown tumor mimicking maxillary sinus mucocele as the first manifestation of
      primary hyperparathyroidism.
AB  - We describe the first case of brown tumor mimicking a maxillary sinus mucocele as
      the first manifestation of the patient's primary hyperparathyroidism. A 34-year
      old woman presented with a 14 days history of elevation of the right orbit,
      retrobulbar pain and cheek anesthesia. The CT and MR evaluation showed a mass,
      initially described as mucocele of the right maxillary sinus. The laboratory
      studies revealed hyperparathyroidism. The patient underwent acute surgery, and
      the mass appeared clinically as mucocele. The histological examination of the
      resected lesion revealed changes representing either giant cell granuloma or
      brown tumor. The finding of hyperparathyroidism confirmed the diagnosis of brown
      tumor. To our knowledge, this is the first report of cystic brown tumor mimicking
      a mucocele of the maxillary sinus.

PMID- 21880447
TI  - Oxidative stress markers and phosphorus magnetic resonance spectroscopy in a
      patient with GLUT1 deficiency treated with modified Atkins diet.
AB  - Glucose transporter type 1 deficiency syndrome is an inborn error of glucose
      transport across blood-tissue barriers, and the modified Atkins diet is an
      effective and well-tolerated treatment. To investigate the effects of the
      modified Atkins diet, we examined the cerebrospinal fluid markers and performed
      phosphorus magnetic resonance spectroscopy in a patient with glucose transporter
      type 1 deficiency syndrome before and after the modified Atkins diet.
      Cerebrospinal fluid levels of the oxidative stress markers, 8-hydroxy-2'
      deoxyguanosine and hexanoyl-lysine adduct, were markedly increased above the
      cutoff index and were normalized 18 months after the modified Atkins diet.
      Phosphorus magnetic resonance spectroscopy measurements showed 18% increase of
      PCr/gamma-ATP ratio after the modified Atkins diet. These results suggest that
      the modified Atkins diet may reduce oxidative stress in the brain and improve
      energy reserve capacity, which is important in sustaining electrophysiological
      activities essential for performing brain functions.

PMID- 21880448
TI  - Pontocerebellar hypoplasia type 3 with tetralogy of Fallot.
AB  - We report a male infant with pontocerebellar hypoplasia type 3 and tetralogy of
      Fallot. He showed optic nerve atrophy, progressive microcephaly, severe
      psychomotor developmental delay, and vesicoureteral reflux. Magnetic resonance
      imaging revealed severe hypoplasia of the cerebellar vermis and hemisphere, and
      of the brainstem including the pons, and simplified gyral patterns in bilateral
      frontal lobes. An unknown etiology differing from other cases of PCH type 3 might
      have caused not only optic nerve atrophy and hypoplasia of the cerebellum and
      brainstem, but also cerebral and visceral malformations. To the best of our
      knowledge, this represents the first report of pontocerebellar hypoplasia with
      congenital cardiac malformation.

PMID- 21880449
TI  - Disorders of BH4 metabolism and the treatment of patients with 6-pyruvoyl
      tetrahydropterin synthase deficiency in Taiwan.
AB  - 6-Pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is the most frequent form
      of tetrahydrobiopterin (BH4) deficiency related to hyperphenylalaninemia (HPA).
      PTPS deficiency may not only cause a typical phenylketonuric phenotype, but is
      also accompanied by various neurological signs and symptoms due to impaired
      synthesis of catecholamines and serotonin. The treatment of PTPS deficiency is
      aimed at normalizing phenylalanine levels and brain neurotransmitters. The BH4
      can be administered to normalize phenylalanine (PHE) levels easily, but, owing to
      severe side effects, the neurotransmitters, L-DOPA and 5-hydroxytryptophan,
      should be administered for these patients very carefully. However, optimal dosage
      of the neurotransmitters for PTPS deficiency patients is difficult to be
      determined. Several reports have described unsatisfied outcomes in a large
      percentage of patients with PTPS deficiency, despite early detection and
      treatment. Between 1988 and 2000, 12 newborns with PTPS deficiency identified by
      newborn screening were referred and received early treatment at our hospital. The
      mean IQ score of these 12 patients was 96.7 (+/-9.7; range: 86-119), which is
      considerably higher than previous reports of other populations of PTPS-deficient
      patients. In this report, we reviewed the disorders of BH4 briefly and then
      described treatments of our PTPS-deficient patients.

PMID- 21880450
TI  - Quantitative determination of methylnaltrexone in human serum using liquid
      chromatography-tandem mass spectrometry.
AB  - Methylnaltrexone (MNTX) is a novel peripherally acting MU-opioid antagonist that
      prevents peripheral side effects of opioid drugs such as constipation without
      affecting the analgesia. We developed a selective and sensitive assay to measure
      MTNX concentrations in human serum. The drug was measured after protein
      precipitation with perchloric acid using naltrexone as internal standard and
      liquid chromatography-tandem mass spectrometry (LC-MS/MS) for detection. The
      chromatography was performed isocratically on a RP18 column using 25 mM ammonium
      acetate buffer (pH 4)/acetonitrile (90%/10%; flow rate 200 MUl/min) as mobile
      phase. The MS/MS analysis was performed in positive ionization mode monitoring
      the m/z transitions 356.4/284.2 for MNTX and 342.4/324.2 for naltrexone. The
      method was validated according to selectivity, linearity, accuracy, precision,
      recovery, matrix effects and stability. The validation range for MNTX in serum
      was 0.5-250 ng/ml. The developed LC-MS/MS was shown to be valid and successfully
      applied to measure serum-concentration-time curves of MNTX in a pilot study in
      healthy volunteers.

PMID- 21880451
TI  - Barcode lateral flow immunochromatographic strip for prostate acid phosphatase
      determination.
AB  - A barcode semiquantitative lateral flow immunochromatographic strip for prostate
      acid phosphatase (PAP) was developed, in which the monoclonal antibody specific
      for PAP was labeled to gold nanoparticle and another monoclonal antibody was
      immobilized on nitrocellulose membrane in the barcode fashion respectively. Based
      on the stepwise capture of analyte, the system expresses the concentration of PAP
      in nanogram range as four distinct ladder bars in 30 min, therefore, which could
      be detected directly by naked eye or image analyzer. Serum PAP from 65 patients
      was detected with this method and compared with enzyme linked immunosorbent assay
      (ELISA). There is a good agreement between the methods. Its easily readable
      result, and also its simplicity and low cost offers an alternative for testing
      PAP. By incorporating with different specific antibody, the assay can be further
      extended to detect a variety of analytes with clinical importance.

PMID- 21880452
TI  - Identification, characterization and quantification of new impurities by LC
      ESI/MS/MS and LC-UV methods in rivastigmine tartrate active pharmaceutical
      ingredient.
AB  - Six impurities were detected at trace level in rivastigmine tartrate drug
      substance by a newly developed high performance liquid chromatography method.
      Three impurities were characterized rapidly and three impurities were found to be
      unknown. The unknown impurities were enriched and identified with a combination
      of semi-preparative HPLC and LC/MS/MS techniques. Proposed structures were
      further confirmed by characterization using NMR, FT-IR, and EA techniques of
      impurity standards. Based on the spectroscopic, spectrometric and elemental
      analysis data unknown impurities were characterized as 3-[1
      (dimethylamino)ethyl]phenyl N-ethyl-N-methyl carbamate N-oxide, ethyl-methyl
      carbamic acid 4-(1-dimethylamino-ethyl)-phenyl ester and ethyl-methyl-carbamic
      acid 2-(1-dimethylamino-ethyl)-phenyl ester. A plausible mechanism for the
      formation of these impurities is also proposed. The method was validated
      according to ICH guidelines for fourteen impurities to demonstrate specificity,
      precision, linearity, accuracy and stability indicating nature of the method.
      Regression analysis showed correlation coefficient value greater than 0.999 for
      rivastigmine tartrate and its impurities. Accuracy of the method was established
      based on the recovery obtained between 93.41 and 113.33% for all impurities.

PMID- 21880453
TI  - Identification of the absorbed components and metabolites in rat plasma after
      oral administration of Rhizoma Chuanxiong decoction by HPLC-ESI-MS/MS.
AB  - An HPLC-ESI-MS/MS method was established to identify the absorbed components and
      metabolites in rat plasma after oral administration of Rhizoma Chuanxiong
      decoction (RCD), a well-known traditional Chinese medicine. By comparing the
      extracted ion chromatograms (EICs) obtained from dosed rat plasma, blank rat
      plasma and RCD, a total of 25 compounds were detected in dosed rat plasma. Among
      them, 13 compounds were absorbed into rat plasma in prototype and identified as
      ferulic acid, senkyunolide J, senkyunolide I, senkyunolide D or 4,7-dihydroxy-3
      butylphthalide, senkyunolide F, senkyunolide M, senkyunolide Q, senkyunolide A, E
      butylidenephthalide, E-ligustilide, neocnidilide, Z-ligustilide, levistolide A,
      according to the retention times, UV, MS, MS/MS spectra. In addition, 12
      conjugated metabolites including 6 senkyunolide I-related metabolites, 4
      senkyunolide J-related metabolites and 2 butylidenephthalide-related metabolites
      were also detected and identified by comparing their MS, MS/MS spectra with that
      of corresponding original components. Conjugated with glutathione, cysteine,
      glucuronic acid and sulphuric acid were the main metabolic reactions of
      phthalides. Finally the in vivo metabolic pathways of chemical constituents of
      Chuanxiong in rat plasma were proposed in this study.

PMID- 21880454
TI  - Application of a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method
      to the pharmacokinetics of ON01910 in brain tumor-bearing mice.
AB  - ON01910 is a small molecular weight benzyl styryl sulfone currently under
      investigation as a novel anticancer agent. The purpose of the investigation was
      to develop a sensitive and reproducible liquid chromatography-tandem mass
      spectrometry (LC/MS/MS) method to quantitate levels of ON01910 in small amounts
      of five biological matrices; mouse plasma, feces, urine, normal brain and brain
      tumor. For all matrices, protein precipitation sample preparation was used that
      led to linear calibration curves with coefficients of determination greater than
      0.99. The lower limit of quantitation (LLOQ) for all matrices was 5 ng/ml except
      that for mouse urine which was 10 ng/ml. The calibration standard curves were
      reproducible for all matrices with inter- and intra-day variability in precision
      and accuracy being less than 15% at all quality control concentrations except for
      the LLOQ in mouse plasma for which the accuracy was within 17%. The assay was
      successfully applied to characterize the systemic pharmacokinetics of ON01910 as
      well as its disposition in brain and brain tumor in mice. ON01910 exhibited a
      clearance of 3.61+/-0.85 l/h/kg and a half life of 8.66+/-3.30 h at 50 mg/kg dose
      given I.V.

PMID- 21880455
TI  - Rapid simultaneous analysis of cyclooxygenase, lipoxygenase and cytochrome P-450
      metabolites of arachidonic and linoleic acids using high performance liquid
      chromatography/mass spectrometry in tandem mode.
AB  - Eicosanoids are oxidized arachidonate-derived lipid products generated by
      cyclooxygenase, lipoxygenase and cytochrome P-450 pathways. They are involved in
      diverse processes in health and disease and they are highly bioactive. Gas
      chromatography and enzyme immunoassays were used to quantify these mediators in
      the past. However, the recent availability of high-sensitivity liquid
      chromatography-mass spectrometry has provided a new approach for quantification
      that minimizes the sample size and the required preparation. This paper describes
      a rapid and simple technique for the simultaneous quantitative analysis of
      prostaglandin (PG) E(2) and PGJ(2); leukotrienes (LT) B(4) and D(4); 5-, 12-, 15-
      and 20-hydroxyeicosatetraenoic acids (HETEs); 13-hydroxyoctadecadienoic acid (13
      HODE); 5,6-, 8,9-, 11,12- and 14,15-epoxyeicosatrienoic acids (EETs); and 11,12-
      and 14,15-dihydroxieicosatrienoic acids (DHETs) in cell culture supernatants and
      urine. We simultaneously analyzed 14 arachidonic acid metabolites representative
      from the three pathways, together with 13-HODE, a linoleic-derived product. Solid
      phase extraction was used for the sample preparation. The recoveries obtained
      ranged from 25% to 100%, depending on the metabolites. The LC/MS/MS method used
      the gradient on a C(18) column and electrospray ionization in negative ion
      detection mode. The method was optimized for sensitivity and for separation
      within 20 min. The linear ranges of the calibration curves were 0.1-200 ng/ml for
      PGE(2), PGJ(2), LTB(4), 5-HETE, 12-HETE, 15-HETE, 13-HODE, 11,12-EET, 11,12-DHET
      and 14,15-DHET, and 1-200ng/ml for LTD(4), 20-HETE, 5,6-EET, 8,9-EET and 14,15
      EET. The advantages of this method include minimal sample preparation, high
      sensitivity and elimination of the problem associated with thermal instability in
      gas chromatography analysis.

PMID- 21880456
TI  - ACCF/AHA methodology for the development of quality measures for cardiovascular
      technology: a report of the American College of Cardiology Foundation/American
      Heart Association Task Force on Performance Measures.
AB  - Consistent with the growing national focus on healthcare quality, the American
      College of Cardiology Foundation (ACCF) and the American Heart Association (AHA)
      have taken a leadership role over the past decade in developing measures of the
      quality of cardiovascular care by convening a joint ACCF/AHA Task Force on
      Performance Measures. The Task Force is charged with identifying the clinical
      topics appropriate for the development of performance measures and with
      assembling writing committees composed of clinical and methodological experts in
      collaboration with appropriate subspecialty societies. The Task Force has also
      created methodology documents that offer guidance in the development of process,
      outcome, composite, and efficiency measures. Cardiovascular performance measures
      using existing ACCF/AHA methodology are based on Class I or Class III guidelines
      recommendations, usually with Level A evidence. These performance measures, based
      on evidence-based ACCF/AHA guidelines, remain the most rigorous quality measures
      for both internal quality improvement and public reporting. However, many of the
      tools for diagnosis and treatment of cardiovascular disease involve advanced
      technologies, such as cardiac imaging, for which there are often no underlying
      guideline documents. Because these technologies affect the quality of
      cardiovascular care and also have the potential to contribute to cardiovascular
      health expenditures, there is a need for more critical assessment of the use of
      technology, including the development of quality and performance measures in
      areas in which guideline recommendations are absent. The evaluation of quality in
      the use of cardiovascular technologies requires consideration of multiple
      parameters that differ from other healthcare processes. The present document
      describes methodology for development of 2 new classes of quality measures in
      these situations, appropriate use measures and structure/safety measures.
      Appropriate use measures are based on specific indications, processes, or
      parameters of care for which high level of evidence data and Class I or Class III
      guideline recommendations may be lacking but are addressed in ACCF appropriate
      use criteria documents. Structure/safety measures represent measures developed to
      address structural aspects of the use of healthcare technology (e.g., laboratory
      accreditation, personnel training, and credentialing) or quality issues related
      to patient safety when there are neither guidelines recommendations nor
      appropriate use criteria. Although the strength of evidence for appropriate use
      measures and structure/safety measures may not be as strong as that for formal
      performance measures, they are quality measures that are otherwise rigorously
      developed, reviewed, tested, and approved in the same manner as ACCF/AHA
      performance measures. The ultimate goal of the present document is to provide
      direction in defining and measuring the appropriate use-avoiding not only
      underuse but also overuse and misuse-and proper application of cardiovascular
      technology and to describe how such appropriate use measures and structure/safety
      measures might be developed for the purposes of quality improvement and public
      reporting. It is anticipated that this effort will help focus the national
      dialogue on the use of cardiovascular technology and away from the current
      concerns about volume and cost alone to a more holistic emphasis on value.

PMID- 21880457
TI  - Trends in the national outcomes and costs for claudication and limb threatening
      ischemia: angioplasty vs bypass graft.
AB  - PURPOSE: Debate exists as to the benefit of angioplasty vs bypass graft in the
      treatment of lower extremity peripheral vascular disease. The associated costs
      are poorly defined in the literature. We sought to determine national estimates
      for the costs, utilization, and outcomes of angioplasty and bypass graft for the
      treatment of both claudication and limb threat. METHODS: We searched the
      Nationwide Inpatient Sample (NIS) database (1999-2007), identifying patients who
      had an identifiable International Classification of Disease (ICD)-9 diagnosis
      code of atherosclerotic disease (claudication [440.21] or limb threat [440.22
      440.24]). Of these, only patients who underwent intervention of angioplasty +/-
      stent (percutaneous transluminal angioplasty [PTA; 39.50-39.90]), peripheral
      bypass graft (BPG; 39.29) or aortofemoral bypass (ABF; 39.25) were included. We
      compared demographics, costs, and comorbidities, as well as multivariable
      adjusted outcomes of in-hospital mortality and major amputation. Additionally, we
      used the New Jersey State Inpatient and Ambulatory databases in order to better
      understand the influence of outpatient procedures on current volume and trends.
      RESULTS: There were 563,143 patients identified (PTA: 38%, BPG: 50%, ABF: 6%;
      5.1%: multiple procedure codes). Patients who had PTA and BPG were similar in age
      (70.4 vs 69.5 years) but older than patients who had ABF (61.8 years, P < .01).
      Patients who underwent PTA were more often women (PTA: 46%, BPG: 42%, ABF: 45.2%;
      P < .01). Average costs for PTA increased over 60% for claudication between 2001
      and 2007 ($8670 to $14,084) and limb threat ($13,903 to $23,196). For BPG,
      average costs increased 36% for both claudication ($9322 to $12,681) and limb
      threat ($16,795 to $22,910). In 2007, the average cost per procedure of PTA was
      higher than BPG for both claudication ($13,903 vs $12,681; P = .02) and limb
      threat ($23,196 vs $22,910; P = .04). The number of patients per year undergoing
      PTA increased threefold (15,903 to 46,138) for claudication and limb threat (6752
      to 19,468). For BPG, procedures per year decreased approximately 40% for both
      claudication (13,625 to 9108) and limb threat (25,575 to 13,762). In-hospital
      mortality was similar for PTA and BPG groups for claudication (0.1% vs 0.2%; P =
      .04) and limb threat (2.1% vs 2.6%; P < .01). In-hospital amputation rates were
      significantly higher for patients who had PTA (7%) than BPG (3.9%, odds ratio
      [OR], 1.67 [1.49-1.85]; P < .01) or patients who underwent ABF (3.0%; OR, 2.32
      [1.79, 3.03]; P < .01). CONCLUSION: PTA has altered the treatment paradigm for
      lower limb ischemia with an increase in costs and procedures. It is unclear if
      this represents an increase in patients or number of treatments per patient.
      Although mortality is slightly lower with PTA for all indications, amputation
      rates for limb-threat patients appear higher, as does the average cost.
      Longitudinal studies are necessary to determine the appropriateness of PTA in
      both claudication and limb-threat patients. The mortality benefit with PTA may be
      ultimately lost, and average costs elevated, if multiple interventions are
      performed on the same patients.

PMID- 21880458
TI  - Total vs hemi-aortic arch transposition for hybrid aortic arch repair.
AB  - OBJECTIVE: To compare the outcomes of total aortic arch transposition (TAAT) vs
      hemi-aortic arch transposition (HAAT) for hybrid aortic arch repair. METHODS: A
      systematic search was performed using PubMed between November 1998 and May 2010
      by two independent observers. Studies included reporting on patients treated by
      TAAT or HAAT and stent grafting in a proximal landing zone 0 or 1 by Ishimaru,
      respectively. Further articles were identified by following MEDLINE links, by
      cross-referencing from the reference lists, and by following citations for these
      studies. Case reports and case series of less than five patients were excluded.
      Primary technical and initial clinical success, perioperative, and late morbidity
      and mortality were extracted per study and were meta-analyzed. RESULTS: Fourteen
      studies were included in the statistical analysis. The number of reported
      patients totaled 130 for TAAT/zone 0 and 131 for HAAT/zone 1. The primary
      technical success rate was significantly higher in zone 0 than 1 (95% vs 83%;
      odds ratio [OR], 4.0; 95% confidence interval [CI], 1.47-10.88; P = .0069), due
      to significantly higher primary type I or III endoleak rates in zone 1 (15.48% vs
      3.97%; P = .0050). Reintervention rates were significantly higher in zone 1
      (25.81% vs 12.00%; P = .0321). Initial clinical success rates were comparable
      between zone 0 and 1 (88% vs 85%; OR, 1.35; 95% CI, 0.61-3.02; P = .5354). In
      hospital mortality was higher in zone 0 than 1 (8.46% vs 4.58%; P = .2212).
      CONCLUSION: The more invasive TAAT allows a better landing zone at the cost of
      higher perioperative mortality, therefore, patient selection is crucial.

PMID- 21880459
TI  - Utility of new classification based on clinical and lesional factors after self
      expandable nitinol stenting in the superficial femoral artery.
AB  - BACKGROUND: The aim of this study was to investigate the predictive value of
      clinical classification schemes that assess primary patency after self-expandable
      nitinol stent in the superficial femoral artery (SFA). METHODS: This study was a
      multicenter retrospective study of prospective databases. From April 2004 to
      December 2009, 1001 limbs (807 patients) that underwent successful nitinol stent
      implantation for de novo SFA lesions were identified and analyzed. Primary
      patency was defined as treated vessel without restenosis (defined as >2.4 of peak
      systolic velocity ratio by duplex) and repeat revascularization. Six items were
      included in the classification: female, diabetes, dialysis, critical limb
      ischemia (CLI), lesion length > 150 mm, and poor runoff; the FeDCLIP score. A
      lesion length >150 mm was scored as 2 points. The others were assigned 1 point
      each. The scores of 0 to 2, 3 to 4, and >=5 points were classified as low-,
      moderate-, and high-risk patients, respectively. Outcome measures were primary
      and secondary patency and all-cause mortality up to 6 years in each risk group.
      RESULTS: The mean follow-up interval was 26.8 +/- 14.6 months. Primary patencies
      were 85.7%, 77.3%, and 74.2% in the low-risk group; 71.5%, 54.7%, and 51.9% in
      the moderate-risk group; and 53.0%, 24.3%, and 20.8% in the high-risk group at 1,
      3, and 5 years, respectively. The secondary patencies were 94.6%, 92.3%, and
      90.8% in the low-risk group; 89.5%, 83.1%, and 83.1% in the moderate-risk group;
      and 82.7%, 73.1%, and 73.1% in the high-risk group at 1, 3, and 5 years,
      respectively. There were significant differences in primary and secondary patency
      among the three risk groups (P < .0001 and P < .0001, respectively). Overall
      survival rates were 96.8%, 89.5%, and 81.8% in the low-risk group; 91.5%, 74.4%,
      and 68.7% in the moderate-risk group; and 78.2%, 63.2%, and 48.7% in the high
      risk group at 1, 3, and 5 years, respectively. There were also significant
      differences in mortality (P < .0001). CONCLUSIONS: New classification schemes
      based on FeDCLIP score were useful for risk stratification in vessel patency and
      mortality after self-expandable nitinol stenting for SFA disease.

PMID- 21880460
TI  - Magnetic resonance imaging-guided navigation with a thermoplastic shell for
      breast-conserving surgery.
AB  - BACKGROUND: The aim of this study was to evaluate the accuracy of a magnetic
      resonance imaging (MRI) marking technique with a drape-type thermoplastic shell
      for planning breast-conserving surgery (BCS). METHODS: A prospective review was
      performed on 35 consecutive patients who underwent MRI in the supine position and
      used the specified MRI marking technique. Eleven cases underwent pre-operative
      chemotherapy and 24 cases did not. After immobilizing the breast mound with a
      drape-type thermoplastic shell, patients underwent MRI, and the location of the
      lesion was marked on the shell. Resection lines were dyed blue by indigo carmine,
      which was pushed through the pores of the shell. Specimens obtained during BCS
      were sliced into 5-mm contiguous sections, and the margin was assessed for each
      specimen. Cancer foci less than 5 mm from the margin were classified as positive.
      RESULTS: Of 35 patients, 33 were included in the analysis; 2 were excluded due to
      a lack of effect of pre-operative chemotherapy. Of these 33 patients, 25 (75.8%)
      had negative margins and 7 (21.2%) had positive margins. CONCLUSIONS: Our MRI
      marking technique may be useful for evaluating the extent of tumors that were
      determined by MRI alone. Long-term outcomes of this technique should be evaluated
      further.

PMID- 21880461
TI  - Liver uptake of biguanides in rats.
AB  - Metformin is an oral antihyperglycaemic agent widely used in the management of
      non-insulin-dependent diabetes mellitus. The liver is the primary target,
      metformin being taken up into human and rat hepatocytes via an active transport
      mechanism. The present study was designed to compare hepatic uptake of two
      biguanides, metformin and phenformin, in vitro and in vivo. In in vitro
      experiments, performed using rat cryopreserved hepatocytes, phenformin exhibited
      a much higher affinity and transport than metformin, with marked differences in
      kinetics. The K(m) values for metformin and phenformin were 404 and 5.17MUM,
      respectively, with CLint (V(max)/K(m)) values 1.58MUl/min per 10(6) cells and
      34.7MUl/min per 10(6) cells. In in vivo experiments, when (14)C-metformin and
      (14)C-phenformin were given orally to male rats at a dose of 50mg/kg, the liver
      concentrations of radioactivity at 0.5 hour after dosing were 21.5MUg eq./g with
      metformin but 147.1MUg eq./g for phenformin, ratios of liver to plasma
      concentrations being 4.2 and 61.3, respectively. In conclusion, the results
      suggest that uptake of biguanides by rat hepatocytes is in line with the liver
      distribution found in vivo, phenformin being more efficiently taken up by liver
      than metformin after oral administration.

PMID- 21880462
TI  - miR-98 regulates cisplatin-induced A549 cell death by inhibiting TP53 pathway.
AB  - To explore the possible microRNAs (miRNAs) in the TP53 pathway and their roles in
      A549 cell death induced by cisplatin, the miRNAs relative to 3'-untranslated
      region (3'-UTR) of TP53 were predicted by microRNA analysis softwares, which
      showed that TP53 expression might be targeted by miR-98, miR-453 and miR-485.
      Then, GFP was used as a reporter gene to reflect whether the 3'-UTR of TP53 was
      targeted by the predicted miRNAs. After pcDNA-GFP-UTR was constructed, the GFP
      expression was estimated in A549 cells by the examination of fluorescence
      microscopy and flow cytometry. The intensity of fluorescence in the miR-98 and
      miR-453 groups decreased significantly compared with the control group. The
      percentage of positive GFP cells in miR-98 and miR-453 groups were 30.24% and
      32.58%, respectively, much lower than that of NC group (41.86%). The TP53
      expression was inhibited after transfection with miR-98/miR-453 by western blot.
      As the factors in TP53 pathway, Bcl-2 expression was found to be enhanced, and
      the expression of miR-34a-c was decreased in A549 cells after miR-98/miR-453
      treatment. Moreover, the expression of miR-98 and Bcl-2 was decreased, while miR
      34a-c and TP53 was increased after A549 treated with cisplatin. Our study
      demonstrated that miR-98 and miR-453 down-regulated TP53 expression by targeting
      the 3'-UTR of TP53, and that cisplatin might inhibit A549 cell growth by miR-98
      regulating TP53 pathway. Our results indicated that TP53 relevant miRNAs might be
      the new targets for gene therapy or new drug design.

PMID- 21880463
TI  - Drug resistance in Mycobacterium tuberculosis clinical isolates from Brazil:
      phenotypic and genotypic methods.
AB  - We determined the susceptibility profile of 80 Mycobacterium tuberculosis (MTB)
      clinical isolates from Brazil against isoniazid (INH) and rifampicin (RIF) drugs
      by two phenotypic methods (Resazurin Microtiter Assay - REMA and BACTECTM MGITTM
      Mycobacterial Detection System). DNA polymorphisms were also determined by PCR
      SSCP in isolates resistant to INH and RIF. BACTECTM MGITTM 960 detected 22
      susceptible isolates to INH and RIF, 48 MDR isolates (resistant at least to INH
      and RIF) and nine mono-resistant isolates (eight to INH and one to RIF). REMA
      performance was determined by Receiver Operating Characteristic curve, whose
      assay was validated utilizing as reference the BACTECTM MGITTM 960 system. ROC
      curve showed cut-off values of 0.0625MUg/mL and 0.125MUg/mL, for INH and RIF,
      respectively. REMA-INH demonstrated sensitivity and specificity of 100% while
      REMA-RIF showed sensitivity of 97.2% and specificity of 100%. PCR-SSCP detected
      DNA polymorphisms in 87.5% and 75.5% of isolates classified as INH-resistant and
      RIF-resistant, respectively. One discordant sample found to RIF (resistant by
      BACTECTM MGITTM 960 and susceptible by REMA) showed no mutation by PCR-SSCP. In
      conclusion, our studies demonstrated that the combination of phenotypic method
      REMA, which allowed rapid detection of MDR-MTB with higher levels of sensitivity
      and specificity, with the genotypic method PCR-SSCP, which demonstrated high
      accuracy in the search of polymorphisms in the resistance genes, proved to be a
      useful strategy to study MDR-MTB clinical isolates from national reference center
      located in Sao Paulo city.

PMID- 21880464
TI  - Antigenic challenge in the etiology of autoimmune disease in women.
AB  - Infection has long been implicated as a trigger for autoimmune disease. Other
      antigenic challenges include receipt of allogeneic tissue or blood resulting in
      immunomodulation. We investigated antigenic challenges as possible risk factors
      for autoimmune disease in women using the Health and Retirement Study, a
      nationally representative longitudinal study, linked to Medicare files, years
      1991-2007. The prevalence of autoimmune disease (rheumatoid arthritis,
      Hashimoto's disease, Graves' disease, systemic lupus erythematosus, celiac
      disease, systemic sclerosis, Sjogren syndrome and multiple sclerosis) was 1.4% in
      older women (95% CI: 1.3%, 1.5%) with significant variation across regions of the
      United States. The risk of autoimmune disease increased by 41% (95% CI of
      incidence rate ratio (IRR): 1.10, 1.81) with a prior infection-related medical
      visit. The risk of autoimmune disease increased by 90% (95% CI of IRR: 1.36,
      2.66) with a prior transfusion without infection. Parity was not associated with
      autoimmune disease. Women less than 65 years of age and Jewish women had
      significantly elevated risk of developing autoimmune disease, as did individuals
      with a history of heart disease or end-stage renal disease. Antigenic challenges,
      such as infection and allogeneic blood transfusion, are significant risk factors
      for the development of autoimmune disease in older women.

PMID- 21880465
TI  - Role of Le Fort type I osteotomy approach in juvenile nasopharyngeal
      angiofibroma.
AB  - Le Fort type I osteotomy is a fracture that extends from the pyriform aperture to
      each of the pterygoid plates, resulting in the detachment of the upper jaw from
      the cranial base. A retrospective study was conducted on 12 patients with
      juvenile nasopharyngeal angiofibroma (JNA) who underwent the Le Fort type I
      approach. Preoperatively, all cases were investigated with computed tomographic
      scans with contrast and angiography with embolisation. This paper highlights the
      surgical technique, results and treatment morbidity. The average age of the
      patients was 21 years, average duration of surgery was 3.2h and average blood
      loss was 550 ml. All cases had significant symptomatic improvement
      postoperatively. At 1 year follow up, the authors encountered dental malocclusion
      in one case and no recurrence of JNA. The Le Fort I osteotomy approach is an
      excellent approach for the excision of JNA because it allows good surgical
      exposure, better haemostasis, is cosmetically more acceptable and has a very low
      morbidity.

PMID- 21880466
TI  - Bilateral dystrophic calcification with bone formation in the face due to
      maxillary antrostomy.

PMID- 21880467
TI  - Purines and neuronal excitability: links to the ketogenic diet.
AB  - ATP and adenosine are purines that play dual roles in cell metabolism and
      neuronal signaling. Acting at the A(1) receptor (A(1)R) subtype, adenosine acts
      directly on neurons to inhibit excitability and is a powerful endogenous
      neuroprotective and anticonvulsant molecule. Previous research showed an increase
      in ATP and other cell energy parameters when an animal is administered a
      ketogenic diet, an established metabolic therapy to reduce epileptic seizures,
      but the relationship among purines, neuronal excitability and the ketogenic diet
      was unclear. Recent work in vivo and in vitro tested the specific hypothesis that
      adenosine acting at A(1)Rs is a key mechanism underlying the success of ketogenic
      diet therapy and yielded direct evidence linking A(1)Rs to the antiepileptic
      effects of a ketogenic diet. Specifically, an in vitro mimic of a ketogenic diet
      revealed an A(1)R-dependent metabolic autocrine hyperpolarization of hippocampal
      neurons. In parallel, applying the ketogenic diet in vivo to transgenic mouse
      models with spontaneous electrographic seizures revealed that intact A(1)Rs are
      necessary for the seizure-suppressing effects of the diet. This is the first
      direct in vivo evidence linking A(1)Rs to the antiepileptic effects of a
      ketogenic diet. Other predictions of the relationship between purines and the
      ketogenic diet are discussed. Taken together, recent research on the role of
      purines may offer new opportunities for metabolic therapy and insight into its
      underlying mechanisms.

PMID- 21880468
TI  - Progressive, potassium-sensitive epileptiform activity in hippocampal area CA3 of
      pilocarpine-treated rats with recurrent seizures.
AB  - Rat hippocampal area CA3 pyramidal cells synchronously discharge in rhythmic
      bursts of action potentials after acute disinhibition or convulsant treatment in
      vitro. These burst discharges resemble epileptiform activity, and are of interest
      because they may shed light on mechanisms underlying limbic seizures. However,
      few studies have examined CA3 burst discharges in an animal model of epilepsy,
      because a period of prolonged, severe seizures (status epilepticus) is often used
      to induce the epileptic state, which can lead to extensive neuronal loss in CA3.
      Therefore, the severity of pilocarpine-induced status epilepticus was decreased
      with anticonvulsant treatment to reduce damage. Rhythmic burst discharges were
      recorded in the majority of slices from these animals, between two weeks and nine
      months after status epilepticus. The incidence and amplitude of bursts
      progressively increased with time after status, even after spontaneous behavioral
      seizures had begun. The results suggest that modifying the pilocarpine models of
      temporal lobe epilepsy to reduce neuronal loss leads to robust network
      synchronization in area CA3. The finding that these bursts increase long after
      spontaneous behavioral seizures begin supports previous arguments that temporal
      lobe epilepsy exhibits progressive pathophysiology.

PMID- 21880469
TI  - Antimicrobial susceptibility of bacterial pathogens associated with community
      acquired respiratory tract infections in Asia: report from the Community-Acquired
      Respiratory Tract Infection Pathogen Surveillance (CARTIPS) study, 2009-2010.
AB  - A multicentre resistance surveillance study [Community-Acquired Respiratory Tract
      Infection Pathogen Surveillance (CARTIPS)] investigating the susceptibilities of
      2963 clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae,
      Moraxella catarrhalis, Klebsiella pneumoniae, meticillin-susceptible
      Staphylococcus aureus (MSSA) and Streptococcus spp. from Asia against 12
      antimicrobial agents was undertaken from 2009 to 2010. Based on the breakpoints
      for oral penicillin V recommended by the Clinical and Laboratory Standards
      Institute, the prevalence of penicillin-non-susceptible S. pneumoniae (PNSSP)
      ranged from 46% to 100%. Azithromycin and clarithromycin exhibited variable
      resistance rates of 0-88% against S. pneumoniae, 0-57% against MSSA and 0-76.5%
      against Streptococcus spp. isolates. The prevalence of extended-spectrum beta
      lactamase-producing K. pneumoniae varied from 5.1% to 58.5%. beta-Lactamase
      production rates amongst H. influenzae isolates ranged from 15% to 46.6% and
      amongst M. catarrhalis isolates from 90% to 100%. Amongst M. catarrhalis
      isolates, macrolide resistance and cefaclor resistance rates of 5.8% and 1.2%,
      respectively, were found, mainly in Mainland China. Levofloxacin resistance rates
      of 0-3.9% with a MIC(90) (minimum inhibitory concentration causing inhibition of
      90% of isolates) of 1-2mg/L and moxifloxacin resistance rates of 0-1.7% with a
      MIC(90) of 0.125-0.5mg/L were found amongst PNSSP isolates. Moxifloxacin was very
      active against Streptococcus spp., H. influenzae and M. catarrhalis isolates,
      with MIC(90) values of 0.125-0.25, 0.032-0.5 and 0.064-0.125mg/L, respectively.
      These results from the CARTIPS study have confirmed some significant regional
      differences in the antimicrobial susceptibilities of S. pneumoniae, MSSA, K.
      pneumoniae, H. influenzae and Streptococcus spp. and emphasise the importance of
      antimicrobial surveillance programmes for guiding empirical therapy and for
      focusing interventional control of antimicrobial resistance in distinct
      geographic areas.

PMID- 21880470
TI  - Repetitive transcranial magnetic stimulation in anorexia nervosa: a pilot study.
AB  - The search for new treatments to improve outcome in people with anorexia nervosa
      continues. This pilot study investigated whether one session of high frequency
      repetitive transcranial magnetic stimulation (rTMS) delivered to the left
      dorsolateral prefrontal cortex reduces eating disorder related symptoms following
      exposure to visual and real food stimuli. Safety and tolerability were also
      assessed. Ten right-handed people with anorexia nervosa underwent one session of
      rTMS. Subjective experiences related to the eating disorder (e.g. urge to
      restrict, feeling full etc.) were assessed before and after rTMS. Non-parametric
      repeated measures tests were used. rTMS was safe and well-tolerated, and resulted
      in reduced levels of feeling full, feeling fat and feeling anxious. Thus, rTMS
      may reduce core symptoms of anorexia nervosa. Future research should establish
      the therapeutic potential of rTMS in anorexia nervosa.

PMID- 21880471
TI  - Progress in correlation spectroscopy at ultra-fast magic-angle spinning: basic
      building blocks and complex experiments for the study of protein structure and
      dynamics.
AB  - Recent progress in multi-dimensional solid-state NMR correlation spectroscopy at
      high static magnetic fields and ultra-fast magic-angle spinning is discussed. A
      focus of the review is on applications to protein resonance assignment and
      structure determination as well as on the characterization of protein dynamics in
      the solid state. First, the consequences of ultra-fast spinning on sensitivity
      and sample heating are considered. Recoupling and decoupling techniques at ultra
      fast MAS are then presented, as well as more complex experiments assembled from
      these basic building blocks. Furthermore, we discuss new avenues in biomolecular
      solid-state NMR spectroscopy that become feasible in the ultra-fast spinning
      regime, such as sensitivity enhancement based on paramagnetic doping, and the
      prospect of direct proton detection.

PMID- 21880472
TI  - Pentraxin 3 as a potential biomarker of acetaminophen-induced liver injury.
AB  - OBJECTIVE: Overdose of acetaminophen (APAP) can lead to severe liver injury in
      humans and experimental animals. Pentraxin-3 (PTX-3) is produced and released by
      several cell types. In this study, we aimed to evaluate whether PTX-3 is a
      potential biomarker in the identification of APAP-induced liver injury. MATERIALS
      AND METHODS: Thirty adult male Wistar rats were randomly divided into three
      groups: control, APAP-1 and APAP-2 groups. APAP-1 (1 g/kg) and APAP-2 (2 g/kg)
      group rats were given APAP by gastric tube. Liver tissues and blood samples were
      obtained for biochemical and histopathological analysis. Biochemical parameters,
      plasma and liver PTX-3 levels and degree of liver necrosis were measured in all
      groups. RESULTS: APAP treatments caused necrosis in liver and accompanied by
      elevated liver PTX-3 levels after 48 h. In APAP-1 and APAP-2 groups when compared
      with control group (7.5+/-3.3 ng/mg protein), mean liver PTX-3 concentrations
      were 14.1+/-3.0 (p=0.032) and 28.5+/-8.2 (p<0.001) ng/mg protein, respectively.
      All rats (100%) in the APAP-2 group had the degree 3 liver necrosis. However 10%,
      40% and 50% of rats had the degree 1, the degree 2 and the degree 3 liver
      necrosis in the APAP-1 group, respectively. The degrees of liver necrosis of the
      APAP-1 and APAP-2 groups were higher than the group of control (p<0.001 and
      p<0.001, respectively). CONCLUSIONS: PTX-3 may have a role in the APAP-induced
      liver injury in the rats. The elevated liver PTX-3 in the APAP-induced hepatic
      necrosis might be a marker of acute histological liver damage. Further
      prospective studies are necessary to clarify the prognostic value of liver PTX-3
      for prediction of histological hepatic necrosis in the APAP-induced liver injury.

PMID- 21880473
TI  - The role of trace elements on hepatitis virus infections: a review.
AB  - The significance of the nutritional roles of trace metals (includes some heavy
      metals) is widely recognized, since these elements are as constituent components
      of many metal proteins and metalloenzymes serum trace metals levels, and their
      ratios are frequently reported to be good marker for diagnosing various diseases.
      Trace metals play an important role in liver disease particularly liver
      degeneration. Influence of trace elements has been studied in a large number of
      viruses belonging to different groups. This review reported the role of some
      trace elements iron (Fe), copper (Cu), cobalt (Co), manganese (Mn) and zinc (Zn)
      as well as toxic elements Pb on hepatitis virus infections.

PMID- 21880474
TI  - Molybdate modulates mitogen and cyclosporin responses of human peripheral blood
      lymphocytes.
AB  - The trace element molybdenum (Mo) is an essential component of key physiological
      systems in animals, plants and microorganisms. The molybdate oxoanion MoO(4)(2-)
      has been demonstrated to cause diverse yet poorly understood biochemical and
      pharmacological effects, such as non-specific inhibition of phosphatases and
      stabilization of steroid receptors. This study aimed to investigate the effects
      of molybdate on the activation of human peripheral blood lymphocytes (hPBLs) ex
      vivo and its potential interaction with the widely used immunosuppressant drug
      cyclosporin A (CsA). Lymphocyte activation was evaluated by performing multiple
      experiments determining blastogenesis in cultured peripheral blood lymphocytes
      obtained from 5 healthy volunteers, following stimulation induced by
      phytohemagglutinin (PHA), in the absence or presence of 0.05-10 mM sodium
      molybdate or/and 2.5-30 MUg/mL CsA. Blastogenesis was assessed by a morphometric
      assay based on the relative proportions of unactivated lymphocytes, activated
      lymphoblasts and cells with aberrant morphology after PHA-induced activation.
      Molybdate concentrations up to 1 mM showed no effect on lymphocyte blastogenesis,
      while higher concentrations exerted immunosuppressive actions on cultured hPBLs.
      Co-administration of 0.1 mM sodium molybdate with CsA, at doses up to 20 MUg/mL,
      induced no alteration in the response of cultured hPBLs to CsA. However,
      molybdate potentiated the immunosuppressive action of higher CsA concentrations,
      implying a likely dose-related synergistic interaction of the two agents in PHA
      stimulated blood lymphocytes. These observations are indicative of the possible
      biological importance of molybdate oxoanions in the modulation of hPBL activation
      that may have pharmacological consequences during the therapeutic application of
      immunomodulatory drugs.

PMID- 21880475
TI  - alpha-Linolenate reduces the dietary requirement for linoleate in the growing
      rat.
AB  - BACKGROUND: We hypothesized that due to the absence of a dietary source of omega
      3 fatty acids, the essential fatty acid (EFA) deficiency model leads to an
      overestimate of linoleic acid (LA) requirements. METHODS: over 7wk, young rats
      consumed an EFA diet containing either 0en% linoleate (0LA) and 0en% alpha
      linolenate (0LNA) or a diet containing 0.5en% LNA plus one of seven levels of
      added LA (0.12-4.0en%; n=6/group). RESULTS: Rats consuming the 0LA-0LNA diet had
      the lowest final body weight, 34-68% lower LA and arachidonate in plasma and
      liver, 87% lower LA in epididymal fat, and an 8-20 fold higher eicosatrienoate in
      plasma, liver and muscle lipids. 0.5LNA completely prevented the lower growth and
      partly prevented the rise in eicosatrienoate seen in the 0LA-0LNA group.
      CONCLUSION: Providing dietary LNA at 0.5 en% reduces the rat's physiological
      requirement for LA by an estimated factor of at least four (0.5en% instead of
      2en%). Since LA requirements in humans are also based on the same flawed model of
      EFA deficiency, it is plausible that they too have been overestimated and should
      therefore be reinvestigated.

PMID- 21880476
TI  - Dietary long-chain n-3 PUFA, gut microbiota and fat mass in early postnatal
      piglet development--exploring a potential interplay.
AB  - Dietary n-3PUFA and gut bacteria, particularly Bacteroidetes, have been suggested
      to be related to adiposity. We investigated if n-3PUFA affected fat storage and
      cecal bacteria in piglets. Twenty-four 4-day-old piglets were allocated to
      formula rich in n-3PUFA (~3E%) from fish oil (FO) or n-6PUFA from sunflower oil
      (SO) for 14 days. We assessed body weight, fat accumulation by dual-energy X-ray
      absorptiometry and microbial molecular fingerprints. Dietary PUFA-composition was
      reflected in higher erythrocyte n-3PUFA in the FO- than the SO-group (P<0.001).
      Principal component analysis revealed group differences in the overall
      microbiotic composition, which involved a larger Bacteroides community in the SO
      group (P=0.02). There was no significant difference in body fat percentage and no
      relationship between fat accumulation and gut Bacteroides. Hence, this study does
      not support an impact of n-3PUFA or microbiota on fat accumulation during the
      postnatal maturation period. The impact of dietary PUFA on the gut Bacteroides
      warrants further investigation.

PMID- 21880477
TI  - Regulation of rat brain polyunsaturated fatty acid (PUFA) metabolism during
      graded dietary n-3 PUFA deprivation.
AB  - Knowing threshold changes in brain lipids and lipid enzymes during dietary n-3
      polyunsaturated fatty acid deprivation may elucidate dietary regulation of brain
      lipid metabolism. To determine thresholds, rats were fed for 15 weeks DHA-free
      diets having graded reductions of alpha-linolenic acid (alpha-LNA). Compared with
      control diet (4.6% alpha-LNA), plasma DHA fell significantly at 1.7% dietary
      alpha-LNA while brain DHA remained unchanged down to 0.8% alpha-LNA, when plasma
      and brain docosapentaenoic acid (DPAn-6) were increased and DHA-selective iPLA(2)
      and COX-1 activities were downregulated. Brain AA was unchanged by deprivation,
      but AA selective-cPLA(2), sPLA(2) and COX-2 activities were increased at or below
      0.8% dietary alpha-LNA, possibly in response to elevated brain DPAn-6. In
      summary, homeostatic mechanisms appear to maintain a control brain DHA
      concentration down to 0.8% dietary DHA despite reduced plasma DHA, when DPAn-6
      replaces DHA. At extreme deprivation, decreased brain iPLA(2) and COX-1
      activities may reduce brain DHA loss.

PMID- 21880478
TI  - Signaling circuitries controlling stem cell fate: to be or not to be.
AB  - The integration of extrinsic and intrinsic signals is required to preserve the
      self-renewal and tissue regenerative capacity of adult stem cells, while
      protecting them from malignant conversion or loss of proliferative potential by
      death, differentiation or senescence. Here we review emerging signaling
      circuitries regulating stem cell fate, with emphasis on epithelial stem cells.
      Wnt, mTOR, GPCRs, Notch, Rho GTPases, YAP and DNA and histone methylases are some
      of the mechanisms that allow stem cells to balance their regenerative potential
      and the initiation of terminal differentiation programs, guaranteeing appropriate
      tissue homeostasis. Understanding the signaling circuitries regulating stem cell
      fate decisions might provide important insights into cancer initiation and
      numerous human pathologies that involve the progressive loss of tissue-specific
      adult stem cells.

PMID- 21880479
TI  - Microbial nitrogen transformation potential in surface run-off leachate from a
      tropical landfill.
AB  - Ammonium is one of the major toxic compounds and a critical long-term pollutant
      in landfill leachate. Leachate from the Jatibarang landfill in Semarang,
      Indonesia, contains ammonium in concentrations ranging from 376 to 929mgNL(-1).
      The objective of this study was to determine seasonal variation in the potential
      for organic nitrogen ammonification, aerobic nitrification, anaerobic nitrate
      reduction and anaerobic ammonium oxidation (anammox) at this landfilling site.
      Seasonal samples from leachate collection treatment ponds were used as an
      inoculum to feed synthetic media to determine potential rates of nitrogen
      transformations. Aerobic ammonium oxidation potential (<0.06mgNL(-1)h(-1)) was
      more than a hundred times lower than the anaerobic nitrogen transformation
      processes and organic nitrogen ammonification, which were of the same order of
      magnitude. Anaerobic nitrate oxidation did not proceed beyond nitrite; isolates
      grown with nitrate as electron acceptor did not degrade nitrite further. Effects
      of season were only observed for aerobic nitrification and anammox, and were
      relatively minor: rates were up to three times higher in the dry season. To
      completely remove the excess ammonium from the leachate, we propose a two-stage
      treatment system to be implemented. Aeration in the first leachate pond would
      strongly contribute to aerobic ammonium oxidation to nitrate by providing the
      currently missing oxygen in the anaerobic leachate and allowing for the growth of
      ammonium oxidisers. In the second pond the remaining ammonium and produced
      nitrate can be converted by a combination of nitrate reduction to nitrite and
      anammox. Such optimization of microbial nitrogen transformations can contribute
      to alleviating the ammonium discharge to surface water draining the landfill.

PMID- 21880481
TI  - Biological removal of inhibitors leads to the improved lipid production in the
      lipid fermentation of corn stover hydrolysate by Trichosporon cutaneum.
AB  - Corn stover (CS) hydrolysate was used as the fermentation feedstock of
      Trichosporon cutaneum CX1 for production of microbial lipid as the potential raw
      material of biodiesel. Two major technical barriers of the lipid fermentation
      were investigated: one was the strong inhibition of lignocellulose degradation
      compounds generated in the CS pretreatment; the other was the low carbon-to
      nitrogen molar ratio (C/N ratio) of the CS hydrolysate. The newly established
      biodetoxification method was applied to remove the inhibitors in the pretreated
      CS. The enhancement of the pretreatment severity and the biodetoxification
      intensity on the lipid fermentation was investigated. The results show that the
      biodetoxification not only efficiently removed the inhibitor substances, but also
      led to the reduction of nitrogen content and the increase of C/N ratio. The cell
      lipid content of T. cutaneum CX1 using the biodetoxified CS hydrolysate reached
      23.5%, which was doubled than that using the non-detoxified value.

PMID- 21880482
TI  - Optimization of fumaric acid production by Rhizopus delemar based on the
      morphology formation.
AB  - The effects of temperature, agitation rate and medium composition, including
      concentrations of glucose, soybean peptone, and inorganic ions, on pellet
      formation and pellet diameter of Rhizopus delemar (Rhizopus oryzae) NRRL1526
      during pre-culture were studied. Inorganic ions and soybean peptone had negative
      and positive effects on pellet formation, respectively. The initial glucose and
      soybean peptone concentrations directly affected pellet diameter. Within a
      certain range, pellet diameter decreased with increased initial substrate
      concentrations; however, above this range there was an opposite trend. Thus,
      optimal concentrations of substrate during pre-culture were beneficial for
      producing small pellets of R. delemar. Furthermore, dry cell mass and yield of
      fumaric acid tended to increase with decreased pellet diameter. Based on the
      pellet morphology optimization, the final fumaric acid concentration was improved
      by 46.13% when fermented in a flask and 31.82% in stirred bioreactor tank
      fermentation.

PMID- 21880480
TI  - Mass spectrometry: come of age for structural and dynamical biology.
AB  - Over the past two decades, mass spectrometry (MS) has emerged as a bone fide
      approach for structural biology. MS can inform on all levels of protein
      organization, and enables quantitative assessments of their intrinsic dynamics.
      The key advantages of MS are that it is a sensitive, high-resolution separation
      technique with wide applicability, and thereby allows the interrogation of
      transient protein assemblies in the context of complex mixtures. Here we describe
      how molecular-level information is derived from MS experiments, and how it can be
      combined with spatial and dynamical restraints obtained from other structural
      biology approaches to allow hybrid studies of protein architecture and movements.

PMID- 21880483
TI  - Modeling of oleaginous fungal biofilm developed on semi-solid media.
AB  - An oleaginous fungus, Mortierella isabellina, able to transform efficiently sugar
      to storage lipid, was used as a model microorganism which develops a biofilm
      structure during the semi-solid fermentation process for the production of
      biodiesel from sweet sorghum. A mathematical model was developed to describe the
      fungal oil production in M. isabellina biofilm. The model describes diffusion and
      consumption of sugars and nitrogen of sweet sorghum and single cell oil
      production in a biofilm, which grows according to the kinetics of double
      substrate limitation (sugars and nitrogen) with sugar inhibition. Experimental
      data from a previous experimental study were used to determine the kinetic
      parameters of the model. Maximum biofilm thickness and the percentage of lipid
      inside the biofilm were estimated using the model at 1892 MUm and 15%,
      respectively. The proposed mathematical model could prove a useful tool for
      designing semi-solid fermentation processes.

PMID- 21880484
TI  - One-step enzymatic production of fatty acid ethyl ester from high-acidity waste
      feedstocks in solvent-free media.
AB  - This work aims to demonstrate the enzymatic production of fatty acid ethyl ester
      biodiesel from highly acidic feedstock in a single-step reaction, without co
      solvents and avoiding the inhibition of the enzyme by ethanol and glycerol.
      Additionally, an empirical equation is proposed to predict the kinetics of the
      production reaction as a function of the used feedstock and catalyst
      concentration. Biodiesel production from highly acidic feedstock perform via
      simultaneous esterification of free fatty acids and transesterification of
      triacylglycerols. Enzymatic catalysis is one of the most promising alternative
      technologies for the biodiesel production. Increasing of the enzymatic
      bioactivity is crucial for the success of such process in industrial scale.
      Currently, stepwise addition of the alcohol or the use of co-solvents have been
      proposed to avoid enzyme inhibition, such strategies add downstream processes to
      the production. These results can be applied to the development economical-viable
      enzymatic production of biodiesel in industrial scale.

PMID- 21880485
TI  - Selecting the right blood glucose monitor for the determination of glucose during
      the enzymatic hydrolysis of corncob pretreated with different methods.
AB  - In order to assess their accuracy for the determination of glucose during the
      enzymatic hydrolysis of pretreated lignocellulosic biomass, four different blood
      glucose monitors (BGMs), each utilizing a different enzymatic mechanism for the
      determination of glucose, were utilized in an experimental setup, which compares
      the efficiency of ionic liquid pretreatment with dilute acid and alkaline
      pretreatments applied on corncob. Among the tested devices, Optium Xceed was
      found to be the most accurate device for the determination of glucose where Accu
      Chek Active was the least accurate BGM, yielding similar results to those
      obtained with DNS method. Based on the HPLC results, the % error values for
      Optium Xceed ranged between 3.9-10.5% for the determination of glucose
      concentration. Upon enzymatic hydrolysis, ionic liquid and alkaline pretreatments
      gave similar glucose yields, which were slightly higher than the dilute acid
      pretreatment, which were 31.9%, 31.0% and 27.8%, respectively, based on untreated
      corncob.

PMID- 21880486
TI  - Discovery of inhibitors of plasminogen activator inhibitor-1: structure-activity
      study of 5-nitro-2-phenoxybenzoic acid derivatives.
AB  - Two novel series of 5-nitro-2-phenoxybenzoic acid derivatives are designed as
      potent PAI-1 inhibitors using hybridization and conformational restriction
      strategy in the tiplaxtinin and piperazine chemo types. The lead compounds 5a,
      6c, and 6e exhibited potent PAI-1 inhibitory activity and favorable oral
      bioavailability in the rodents.

PMID- 21880488
TI  - Pancreatic anticancer activity of a novel geranylgeranylated coumarin derivative.
AB  - A series of hydroxycoumarin derivatives has been synthesized and evaluated
      against human pancreatic PANC-1 cancer cells under nutrient-deprived conditions.
      Several compounds exhibited 100% preferential cytotoxicity at low micromolar
      concentrations under nutrition starvation, and showed no cytotoxicity under
      nutrient-rich conditions. In this study, a novel geranylgeranylated ether
      coumarin derivative 9 was found to exhibit the highest cytotoxic activity of 6.25
      MUM within 24h. The preferential anti-tumor activity exhibited by compound 9
      against PANC-1 under low oxygen and nutrient environment illustrates its great
      potential as a promising lead structure for the development of novel agents to
      combat pancreatic cancer.

PMID- 21880487
TI  - Conformationally constrained analogs of BAY 59-3074 as novel cannabinoid receptor
      ligands.
AB  - To obtain information on the pharmacophoric requirements of the CB1/CB2 partial
      agonist BAY 59-3074 we have synthesized a series of new conformationally
      constrained dibenzofuran (4a-d) and dibenzopyran analogs (5). All constrained
      analogs exhibited reduced binding affinity at both cannabinoid receptor subtypes,
      suggesting that planar conformations of these ligands are less favored by both
      receptors. We also found that 4c, 4d, and 5 exhibited 3- to 12-fold selectivity
      for hCB2 over rCB1 receptors and may serve as new chemotypes for the development
      of CB2-selective cannabinergics.

PMID- 21880489
TI  - Design and synthesis of long acting inhaled corticosteroids for the treatment of
      asthma.
AB  - In this Letter we present data for a novel series of ICS for the treatment of
      asthma. 'Inhalation by design' principles have been applied to a series of highly
      potent steroidal GR agonists, with a focus on optimising the potential
      therapeutic index in human. Pharmacokinetic properties were tuned with high
      intrinsic clearance and low oral bioavailability in mind, to minimise systemic
      exposure and reduce systemically driven adverse events. High CYP mediated
      clearance as well as glucuronidation were targeted to achieve high intrinsic
      clearance coupled with multiple routes of clearance to minimise drug-drug
      interactions. Furthermore, pharmaceutical properties such as stability,
      crystallinity and solubility were considered to ensure compatibility with a dry
      powder inhaler. This work culminated in the identification of the clinical
      candidate 15, which demonstrates preclinically the desired efficacy and safety
      profiles confirming its potential as an inhaled agent for the treatment of
      asthma.

PMID- 21880490
TI  - Synthesis and acrosin inhibitory activities of substituted ethyl 5-(4
      aminophenyl)-1H-pyrazole-3-carboxylate derivatives.
AB  - A series of novel ethyl 5-(4-aminophenyl)-1H-pyrazole-3-carboxylate derivatives
      were designed and synthesized and their in vitro acrosin inhibitory activities
      were evaluated. Most of the compounds exhibited acrosin inhibitory activities.
      Among them, three compounds (5l, 5n, and 5v) were more potent than that of the
      control TLCK. These provide a new structural type for the development of novel
      contraceptive acrosin inhibitory agents.

PMID- 21880491
TI  - Synthesis, structure-activity relationship and in vitro biological evaluation of
      N-arylethyl isoquinoline derivatives as Coxsackievirus B3 inhibitors.
AB  - Currently, there is no approved antiviral drug for the infection caused by
      enteroviruses. A series of novel N-arylethyl isoquinoline derivatives defined
      with substituents on the ring A and C were designed, synthesized and evaluated in
      vitro for their activities against Coxsackievirus B3 (CVB3). The primary
      structure-activity relationship revealed that substituents on the ring A were not
      beneficial for the activity. Among these analogs synthesized, compound 7f bearing
      a methylenedioxy at the R(4) and R(5) positions afforded an anti-CVB3 activity
      and a reasonable selectivity index (SI=26.8); furthermore, 7f exhibited a
      moderate activity against enterovirus 71 (EV71) with SI value of 9.0. Thus it has
      been selected as an anti-enteroviral lead compound for further investigation.

PMID- 21880493
TI  - An enhanced recovery programme for primary total knee arthroplasty in the United
      Kingdom--follow up at one year.
AB  - The concepts of Enhanced Recovery Programmes (ERP) are to reduce peri-operative
      morbidity whilst accelerating patient's rehabilitation resulting in a shortened
      hospital stay following primary joint arthroplasty. These programmes should
      include all patients undergoing surgery and should not be selective. We report a
      consecutive series of 1081 primary total knee arthroplasties undergoing an
      enhanced recovery programme with a one year follow up period. A comparative
      cohort of 735 patients from immediately prior to the enhanced recovery programme
      implementation was also reviewed. The median day of discharge home was reduced
      from post-operative day six to day four (p<0.001) for the ERP group. Post
      operative urinary catheterisation (35% vs. 6.9%) and blood transfusion (3.7% vs.
      0.6%) rates were significantly reduced (p<0.001). Within the ERP group median
      pain scores (0 = no pain, 10 = maximal pain) on mobilisation were three
      throughout hospital stay with 95% of patients ambulating within 24h. No
      statistical difference was found in post-operative thrombolytic events (p=0.35
      and 0.5), infection (p=0.86), mortality rates (p=0.8) and Oxford Knee Scores
      (p=0.99) at follow up. This multidisciplinary approach provided satisfactory post
      operative analgesia allowing early safe ambulation and expedited discharge to
      home with no detriment to continuing rehabilitation, infection or complication
      rates at one year.

PMID- 21880492
TI  - Cryptococcus gattii: a resurgent fungal pathogen.
AB  - Cryptococcus gattii and Cryptococcus neoformans are causal agents of
      cryptococcosis, which manifests as pneumonia and meningitis. C. gattii has
      recently received widespread attention owing to outbreaks in British Columbia,
      Canada and the US Pacific Northwest. The biology of this tree-dwelling yeast is
      relatively unexplored, and there are few clues about how it causes infections in
      humans and animals. In this review, we summarize recent discoveries about C.
      gattii genetics and its ecological niche and highlight areas ripe for future
      exploration. Increased focus on epidemiology, ecological modeling and host
      pathogen interactions is expected to yield a better understanding of this
      enigmatic yeast, and ultimately lead to better measures for its control.

PMID- 21880494
TI  - Cleavable linkers in chemical biology.
AB  - Interest in cleavable linkers is growing due to the rapid development and
      expansion of chemical biology. The chemical constrains imposed by the biological
      conditions cause significant challenges for organic chemists. In this review we
      will present an overview of the cleavable linkers used in chemical biology
      classified according to their cleavage conditions by enzymes, nucleophilic/basic
      reagents, reducing agents, photo-irradiation, electrophilic/acidic reagents,
      organometallic and metal reagents, oxidizing reagents.

PMID- 21880495
TI  - Chemical modifications of resveratrol for improved protein kinase C alpha
      activity.
AB  - Resveratrol (1) is a naturally occurring phytoalexin that affects a variety of
      human disease models, including cardio- and neuroprotection, immune regulation,
      and cancer chemoprevention. One of the possible mechanisms by which resveratrol
      affects these disease states is by affecting the cellular signaling network
      involving protein kinase C alpha (PKCalpha). PKCalpha is a member of the family
      of serine/threonine kinases, whose activity is inhibited by resveratrol. To study
      the structure-activity relationship, several monoalkoxy, dialkoxy and hydroxy
      analogs of resveratrol have been synthesized, tested for their cytotoxic effects
      on HEK293 cells, measured their effects on the membrane translocation properties
      of PKCalpha in the presence and absence of the PKC activator TPA, and studied
      their binding with the activator binding domain of PKCalpha. The analogs showed
      less cytotoxic effects on HEK293 cells and caused higher membrane translocation
      (activation) than that of resveratrol. Among all the analogs, 3, 16 and 25 showed
      significantly higher activation than resveratrol. Resveratrol analogs, however,
      inhibited phorbol ester-induced membrane translocation, and the inhibition was
      less than that of resveratrol. Binding studies using steady state fluorescence
      spectroscopy indicated that resveratrol and the analogs bind to the second
      cysteine-rich domain of PKCalpha. The molecular docking studies indicated that
      resveratrol and the analogs interact with the protein by forming hydrogen bonds
      through its hydroxyl groups. These results signify that molecules developed on a
      resveratrol scaffold can attenuate PKCalpha activity and this strategy can be
      used to regulate various disease states involving PKCalpha.

PMID- 21880497
TI  - Stopping power and mean free path for low-energy electrons in ten scintillators
      over energy range of 20-20,000 eV.
AB  - Systematic calculations of the stopping powers (SP) and inelastic mean free paths
      (IMFP) for 20-20,000eV electrons in a group of 10 important scintillators have
      been carried out. The calculations are based on the dielectric model including
      the Born-Ochkur exchange correction and the optical energy loss functions (OELFs)
      are empirically evaluated because of the lack of available experimental optical
      data for the scintillators under consideration. The evaluated OELFs are examined
      by both the f-sum rule and the calculation of mean ionization potential. The SP
      and IMFP data presented here are the first results for the 10 scintillators over
      the energy range of 20-20,000eV, and are of key importance for the investigation
      of liquid scintillation counting.

PMID- 21880496
TI  - Synthesis, structural, and biological evaluation of bis-heteroarylmaleimides and
      bis-heterofused imides.
AB  - Bis-2,3-heteroarylmaleimides and polyheterocondensed imides joined through
      nitrogen atoms of the N,N'-bis(ethyl)-1,3-propanediamine linker were prepared
      from substituted maleic anhydrides and symmetrical diamines in good to
      satisfactory yields and short reaction times using microwave heating. The novel
      molecules were shown to inhibit proliferation of human tumor cells (NCI-H460 lung
      carcinoma) and rat aortic smooth muscle cells (SMCs) with variable potencies.
      Compound 11a, the most potent one of the series, showed IC(50) values comparable
      to those observed for the leading molecule elinafide in both cell lines, but with
      a higher selectivity toward human tumor cells. Compound 11a affected G1/S phase
      transition of the cell cycle, showed in vitro DNA intercalating activity and in
      vivo antitumor activity. A thorough structural analysis of the 11a-DNA complex
      was also made by mean of NMR and computational techniques.

PMID- 21880498
TI  - Applicability of strain measurements on a contra angle handpiece for the
      determination of alveolar bone quality during dental implant surgery.
AB  - Alveolar bone quality is considered to be an important prognostic factor in
      dental implant stability. Although numerous methods have been described, no
      technique allows for reliable diagnostics. The purpose of this study was to
      determine if strain measurements on the shaft of a contra angle handpiece during
      implant bed preparation could be used for the determination of bone quality.
      Experiments in polyurethane foam and human cadaver bone were conducted to
      investigate whether strain measurements could be correlated with other diagnostic
      parameters, such as the surgeon's tactile sensation during drilling, implant
      insertion torque, implant stability, elastic modulus of bone and bone quality as
      assessed radiographically. Tests were also performed to determine if strain
      measurements could be used to distinguish various types of bone. As axial feed
      and contact pressure during the drilling process could not be standardized under
      simulated clinical conditions, substantial deviations in the time needed to
      complete the drilling occurred. Under controlled circumstances using polyurethane
      foam, this problem could be addressed by a normalization procedure, but great
      variations occurred in human cadaver bone. As bone quality could not be reliably
      determined, especially when a cortical layer was present, strain measurements on
      a contra angle handpiece appears to be inappropriate for this purpose.

PMID- 21880499
TI  - The hypothetical role of congenital hypotonia in the development of early
      coronoid hyperplasia.
AB  - BACKGROUND: Coronoid hyperplasia (CH) is an abnormal bony elongation of a
      histologically normal coronoid process. Its definitive cause remains unknown.
      OBJECTIVES: To analyze the possible implication of congenital hypotonia in the
      pathogenesis of early coronoid overgrowth. PATIENTS AND METHODS: Two infants with
      congenital hypotonia were evaluated for limited mouth aperture. Bilateral CH was
      diagnosed. Transoral coronoidectomy was followed by an early dynamic
      physiotherapy program. RESULTS: Significant improvement of maximum interincisal
      opening was achieved. The review of the scientific literature proved the
      diagnosis of CH in the infant age group is extremely unusual and the etiology of
      the condition is still uncertain. CONCLUSIONS: Besides mouth opening restriction,
      clinical features of coronoid hyperplasia in infants can include suction or
      deglutition anomalies, failure to thrive and recurrent episodes of choking or
      aspiration pneumonia. The authors hypothesize reduced fetal mandibular movements
      and deglutition as a result of congenital hypotonia may lead to relative
      hyperactivity of the temporalis muscle that is not counterbalanced by the infra
      and suprahyoid muscles, thereby facilitating coronoid overgrowth.

PMID- 21880500
TI  - Condylar position indicator and T-scan system II in clinical evaluation of
      temporomandibular intracapsular disease.
AB  - INTRODUCTION: The pathogenesis of temporomandibular joint intracapsular disease
      (TMJI) is multifactorial and its diagnosis is not easy. In this work authors show
      two types of clinical analysis: the Condylar Position Indicator (CPI) and T-Scan
      2 system. MATERIAL AND METHODS: Twenty patients (mean age of 24.5 years) with
      TMJI problem and 10 healthy matched subjects (mean age: 25.4 years) were
      selected. Analysis of TMJI was performed on each patient by means of Condylar
      Position Indicator (CPI) and T-Scan System II tests. RESULTS: Eight patients
      presented vertical symmetrical condylar distraction greater than healthy subjects
      (P-value<0.001). T-Scan showed a difference of Percentage of Force (POF) not
      greater than 5%. Seven patients showed sagittal shift greater than healthy
      subject (P-value<0.001). T-Scan records showed a difference of POF greater than
      5%. Five non-healthy subjects presented sagittal, vertical, transverse shift
      greater than healthy subjects (P-value<0.001). T-Scan records show a difference
      of POF greater than 5%. CONCLUSION: In this work authors present a new method of
      analysis. CPI indicates discrepancy of the condyle position in CO from CR and T
      Scan allows the operator to study all teeth contacts and occlusal forces taking
      place during dynamic jaw movement.

PMID- 21880502
TI  - Evaluating the correlation between the lateral pterygoid muscle attachment type
      and internal derangement of the temporomandibular joint with an emphasis on MR
      imaging findings.
AB  - OBJECTIVES: Disc displacement is accepted as one of major findings in
      temporomandibular disorders. Correlation between lateral pterygoid muscle (LPM)
      attachment type to the disc-condyle complex and TMJ dysfunction has rarely been
      discussed and still not clarified. The purpose of this study was to assess the
      prevalence LPM attachment type to the disc-condyle complex, and to investigate
      whether these attachment types are linked to MR imaging findings of ID and TMJ
      dysfunction in a Turkish population. STUDY DESIGN: Ninety-eight TMJs in 49
      patients (32 males, 17 females, mean age=36 years) with one of either: TMJ
      clicking, TMJ locking, restricted movement of the jaw, or pain in the TMJ region,
      were included. According to the clinical findings and data obtained from MRI
      examinations, TMJs dysfunctions were classified. LPM attachments to the condyle
      disc complex were categorized into three different types. Correlation between TMJ
      dysfunction and LPM attachments to the condyle-disc complex was evaluated.
      RESULTS: Of 98 TMJs in 49 patients (32 males, 17 females, mean age=36 years), 47
      TMJ's (%48) were evaluated as normal, 35 (%35.7) had a disc displacement with
      reduction and 16 (%16.3) TMJ had a disc displacement without reduction. Arthritis
      was seen in 49 TMJ's (%50). LPM attachments to the condyle-disc complex were as
      follows: Type I (29.6%), Type II (40.8%), and Type III (29.6%). There was no
      statistically significant difference between the type of muscle attachment and
      the presence or absence of disc displacement (p=0.481), disc degeneration
      (p=0.752), articular surface degeneration (p=0.117). CONCLUSIONS: There was no
      statistically significant correlation between the LPM attachment types and TMJ
      abnormalities.

PMID- 21880501
TI  - Short-term periodontal and microbiological changes following orthognathic
      surgery.
AB  - OBJECTIVE: Aim of the present study was to evaluate the influence of orthognathic
      surgery on the development of periodontal and microbiological changes. MATERIALS
      AND METHODS: Fifteen consecutively treated patients with a mean age of 24.9+/-7.7
      years receiving orthognathic surgery were included in the present study. Plaque
      index (PI) and concentrations of 11 periodonto-pathogenic bacteria were recorded
      one day prior to surgery (t(0)) and one week (t(1)) and six weeks (t(2)) post
      surgery. In addition, a complete periodontal examination including pocket probing
      depth (PPD), gingival recession (GR), clinical attachment level (CAL), bleeding
      on probing (BOP) and width of keratinized gingiva (WKG) was conducted at t(0) and
      t(2). For statistical analysis, general linear model and paired t-test were
      applied. RESULTS: A significant increase of PI (t(0)-t(1), p=0.037) was followed
      by a significant decrease (t(1)-t(2), p=0.017). Apart from Eikenella corrodens
      (p=0.036), no significant microbiological changes were recorded. PPD
      significantly increased on oral sites (p=0.045) and GR especially on buccal sites
      (p=0.001). In the incision area the development of GR was significantly higher on
      the test (buccal) than on the control sites (oral). Both gingival biotypes were
      affected by GR. CONCLUSIONS: Orthognathic surgery causes statistically
      significant changes of periodontal parameters, but these changes do not
      necessarily impair the aesthetic appearance of the gingival margin.

PMID- 21880504
TI  - Radioprotective efficacy of tocopherol succinate is mediated through granulocyte
      colony stimulating factor.
AB  - The purpose of this study was to elucidate the role of granulocyte colony
      stimulating factor (G-CSF) induced by alpha-tocopherol succinate (TS) in
      protecting mice from total-body irradiation. CD2F1 mice were injected with a
      radioprotective dose of TS and the levels of cytokine in serum induced by TS were
      determined by multiplex Luminex. Neutralization of G-CSF was accomplished by
      administration of a G-CSF antibody and confirmed by cytokine analysis. The role
      of G-CSF on gastrointestinal tissue protection afforded by TS after irradiation
      (11 Gy, 0.6 Gy/min of 60Co gamma-radiation) was determined by analysis of jejunum
      histopathology for crypt, villi, mitotic figures, apoptosis, and cell
      proliferation. Our results demonstrate that TS protected mice against high doses
      of radiation-induced gastrointestinal damage and TS also induced very high levels
      of G-CSF and keratinocyte-derived chemokine (KC) production in peripheral blood
      24 h after subcutaneous administration. When TS-injected mice were administered a
      neutralizing antibody to G-CSF, there was complete neutralization of G-CSF in
      circulating blood, and the protective effect of TS was significantly abrogated by
      G-CSF antibody. Histopathology of jejunum from TS-injected and irradiated mice
      demonstrated protection of gastrointestinal tissue, yet the protection was
      abrogated by administration of a G-CSF antibody. In conclusion, our current study
      suggests that induction of G-CSF resulting from TS administration is responsible
      for protection from 60Co gamma-radiation injury.

PMID- 21880503
TI  - Lower levels of interleukin-12 precede the development of tuberculosis among HIV
      infected women.
AB  - Tuberculosis (TB) is the worldwide leading cause of death among HIV-infected
      individuals, accounting for more than half of AIDS-related deaths. A high risk of
      tuberculosis (TB) has been shown in early stages of the HIV disease, even in the
      presence of normal CD4(+) cell counts. Moreover, the factors that determine
      protective immunity vs. susceptibility to Mycobacterium tuberculosis cannot be
      fully explained by simple changes in IFNgamma levels or a shift from Th1 to Th2
      cytokines. This work investigated the relationship between cytokine expression
      profiles in peripheral blood mononuclear cells (PBMC) and susceptibility to M.
      tuberculosis in 10 HIV+ women who went onto develop TB. RNA transcripts for IL-4,
      IL-4delta2, IL-10, IL-12(p35), IL-13, IL-17A, IFNgamma and TNFalpha were measured
      by real-time quantitative PCR in unstimulated or TB peptide antigen-stimulated
      PBMCs from 10 HIV+ women with positive tuberculin skin tests (TST) and compared
      with HIV-seropositive and seronegative women without previous TB and negative
      TST. Stimulated PBMC cultures showed significantly lower expression of IL-12p35
      (p=0.004) and IL-10 (p=0.026) in the HIV+TB+ group 6-12months before onset of TB
      compared to HIV+TB- women. Unstimulated PBMC from HIV+TB+ women also had lower
      expression of Th2 cytokines [IL-4 (p=0.056) and IL-13 (p=0.050)] compared to
      HIV+TB- women. These results suggest that lower IL-12 production by PBMC in
      response to TB antigens and lower levels of both Th1 and Th2 cytokines by PBMC
      correlate with future development of TB in HIV-infected women and may be
      responsible for their increased susceptibility.

PMID- 21880505
TI  - Local and systemic cellular inflammation and cytokine release in chronic
      obstructive pulmonary disease.
AB  - BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic airway
      inflammatory disease caused by repeated exposure to noxious gases or particles.
      It is now recognized that the disease also features systemic inflammation. The
      purpose of our study was to compare airway and systemic inflammation in COPD to
      that seen in healthy subjects and to relate the inflammation with the disease
      severity. METHODS: Ninety-five COPD patients, encompassing the whole severity
      spectrum of the disease, were recruited from our outpatient clinic and
      rehabilitation center and compared to 33 healthy subjects. Induced sputum and
      blood samples were obtained for measurement of inflammatory cell count.
      Interleukin (IL)-4, IL-6, IL-10, TNF-alpha and IFN-gamma produced by 24h sputum
      and blood cell cultures were measured. RESULTS: Compared to healthy subjects,
      COPD exhibited a prominent airway neutrophilic inflammation associated with a
      marked IL-10, IL-6 and TNF-alpha release deficiency that contrasted with a raised
      IFN-gamma production. Neutrophilic inflammation was also prominent at blood level
      together with raised production of IFN-gamma, IL-10 and TNF-alpha. Furthermore,
      sputum neutrophilia correlated with disease severity assessed by GOLD stages.
      Likewise the extent of TNF-alpha release from blood cells also positively
      correlated with the disease severity but negatively with that of sputum cell
      culture. Blood release of TNF-alpha and IL-6 negatively correlated with body mass
      index. Altogether, our results showed a significant relationship between cellular
      marker in blood and sputum but poor relationship between local and systemic
      release of cytokines. CONCLUSIONS: COPD is characterized by prominent
      neutrophilic inflammation and raised IFN-gamma production at both bronchial and
      systemic level. Overproduction of TNF-alpha at systemic level correlates with
      disease severity and inversely with body mass index.

PMID- 21880507
TI  - Summary of the diverse situation of similar biotherapeutic products in the
      selected countries (August 2010).
AB  - The WHO guidelines on evaluating similar biotherapeutic products (SBPs) were
      adopted by the Expert Committee on Biological Standardization in 2009. The
      fundamental messages of the guidelines are that a) generic approach is not
      suitable for licensing SBPs, b) only products that have been subjected to a
      comparability exercise and show similarity to the reference biotherapeutic
      product (RBP) in terms of their quality, safety and efficacy are defined as SBPs,
      and c) the products that are not shown to be similar to the originator products
      as indicated in the guidelines should neither be described as "similar" nor
      called SBPs. In view of these, the products which have not been subjected to a
      head to head comparison with the RBP should be referred to as another term, e.g.
      'non-innovator' therapeutic products. In order to review the current situation in
      each country, a survey was planned in line with the implementation workshop of
      the guidelines in August 2010. The results show that the diversity of regulatory
      framework for licensing SBPs and the ambiguous use of the terms, 'similar' or
      'generic', present considerable challenges for the future use of SBPs.

PMID- 21880506
TI  - Therapeutic potential of Tregs to treat rheumatoid arthritis.
AB  - There is accumulating evidence for regulatory T cell defects in rheumatoid
      arthritis and that some biologic interventions, in particular anti-TNF, can
      target this population. Despite the challenges in defining regulatory T cells in
      patients, there are a number of approaches currently being developed to utilise
      their potent immunosuppressive properties. Through genetic manipulation Tregs can
      be generated ex vivo or in vivo that target antigens present in the inflamed
      joint. Here we discuss these approaches, their refinement to restore tolerance in
      patients with rheumatoid arthritis, and strategies to prevent their conversion
      towards a Th17 phenotype.

PMID- 21880508
TI  - Intended use of reference products & WHO International Standards/Reference
      Reagents in the development of similar biological products (biosimilars).
AB  - Reference Products and WHO International Standards/Reference Reagents have roles
      to play in the development and characterization of similar biological products
      (SBPs). However, these roles are distinct and non-interchangeable. The uses of
      these materials and their limitations are considered in this paper.

PMID- 21880509
TI  - Examining associations of circulating endotoxin with nutritional status,
      inflammation, and mortality in hemodialysis patients.
AB  - OBJECTIVE: Lipopolysaccharide or endotoxin constitutes most part of the outer
      portion of the cell wall in the gram-negative bacteria. Subclinical endotoxemia
      could contribute to increased inflammation and mortality in hemodialysis (HD)
      patients. Endotoxin level and clinical effect are determined by its soluble
      receptor sCD14 and high-density lipoprotein. We examine the hypothesis that
      endotoxin level correlates with mortality. METHODS: In this cohort study,
      endotoxin levels were measured in 306 long-term HD patients who were then
      followed up for a maximum of 42 months. Soluble CD14 and cytokines levels were
      also measured. RESULTS: The mean (+/-SD) endotoxin level was 2.31 +/- 3.10 EU/mL
      (minimum: 0.26 EU/mL, maximum: 22.94 EU/mL, interquartile range: 1.33 EU/mL,
      median: 1.27 EU/mL). Endotoxin correlated with C-reactive protein (r = 0.11, P <
      .04). On multivariate logistic regression analysis, high body mass index and low
      high-density lipoprotein (HDL) cholesterol levels were associated with higher
      endotoxemia (endotoxin below or above of median). In multivariate Cox regression
      analysis adjusted for case-mix and nutritional/inflammatory confounders,
      endotoxin levels in the third quartile versus first quartile were associated with
      a trend toward increased hazard ratio for death (hazard ratio: 1.83, 95%
      confidence interval: 0.93 to 3.6, P = .08). CONCLUSIONS: In this HD cohort, we
      found associations between endotoxemia and C-reactive protein, body composition,
      and HDL. Moderately high endotoxin levels tended to correlate with increased
      mortality than the highest circulating endotoxin level. Additional studies are
      required to assess the effect of endotoxemia on mortality in dialysis population.

PMID- 21880510
TI  - A comparison of endotracheal bioimpedance cardiography and transpulmonary
      thermodilution in cardiac surgery patients.
AB  - OBJECTIVES: The authors hypothesized that bioimpedance cardiography measured by
      the Endotracheal Cardiac Output Monitor (ECOM; ConMed, Utica, NY) is a convenient
      and reliable method for both cardiac index (CI) assessment and prediction in
      fluid responsiveness. DESIGN: A prospective observational study. SETTING: A
      teaching university hospital. PARTICIPANTS: Twenty-five adult patients.
      INTERVENTIONS: Admission to the intensive care unit after conventional cardiac
      surgery and investigation before and after a fluid challenge. MEASUREMENTS AND
      MAIN RESULTS: Simultaneous comparative CI data points were collected from
      transpulmonary thermodilution (TD) and ECOM. Correlations were determined by
      linear regression. Bland-Altman analysis was used to compare the bias, precision,
      and limits of agreement. The percentage error was calculated. Pulse-pressure
      variations (PPVs) and stroke-volume variations (SVVs) before fluid challenge were
      collected to assess their discrimination in predicting fluid responsiveness. A
      weak but statistically significant relationship was found between CI(TD) and
      CI(ECOM) (r = 0.31, p = 0.03). Bias, precision, and limits of agreement between
      CI(TD) and CI(ECOM) were 0.08 L/min/m(2) (95% confidence interval, -0.11 to
      0.27), 0.68 L/min/m(2), and -1.26 to 1.42 L/min/m(2), respectively. The
      percentage error was 51%. A nonsignificant positive relationship was found
      between percent changes in CI(TD) and CI(ECOM) after fluid challenge (r = 0.37, p
      = 0.06). Areas under the ROC curves for both PPV and SVV to predict fluid
      responsiveness were 0.86 (95% confidence interval, 0.67-1.06) and 0.89 (95%
      confidence interval, 0.74-1.04, respectively; p = 0.623). CONCLUSIONS: Continuous
      measurements of CI under dynamic conditions are consistent and easy to obtain
      with ECOM although not interchangeable with transpulmonary thermodilution. SVV
      given by ECOM is a dynamic parameter that predicts fluid responsiveness with good
      accuracy and discrimination.

PMID- 21880511
TI  - The varieties of inner speech: links between quality of inner speech and
      psychopathological variables in a sample of young adults.
AB  - A resurgence of interest in inner speech as a core feature of human experience
      has not yet coincided with methodological progress in the empirical study of the
      phenomenon. The present article reports the development and psychometric
      validation of a novel instrument, the Varieties of Inner Speech Questionnaire
      (VISQ), designed to assess the phenomenological properties of inner speech along
      dimensions of dialogicality, condensed/expanded quality, evaluative/motivational
      nature, and the extent to which inner speech incorporates other people's voices.
      In response to findings that some forms of psychopathology may relate to inner
      speech, anxiety, depression, and proneness to auditory and visual hallucinations
      were also assessed. Anxiety, but not depression, was found to be uniquely
      positively related to both evaluative/motivational inner speech and the presence
      of other voices in inner speech. Only dialogic inner speech predicted auditory
      hallucination-proneness, with no inner speech variables predicting levels of
      visual hallucinations/disturbances. Directions for future research are discussed.

PMID- 21880512
TI  - The impact of incidental identification on the stage at presentation of lower
      gastrointestinal carcinoids.
AB  - BACKGROUND: Over the past 3 decades, there has been a significant increase in the
      incidence of gastrointestinal carcinoid tumors in the United States. Incidentally
      discovered carcinoids in the lower gastrointestinal tract have probably
      contributed to this increase. In this study we aimed to compare the
      clinicopathologic characteristics of incidentally discovered carcinoids of the
      small and large bowel with those identified as a result of symptoms. STUDY
      DESIGN: We performed a retrospective review of 58 consecutive patients with
      nonappendiceal gastrointestinal carcinoids: 30 small bowel and 28 large bowel. We
      compared asymptomatic patients with lower gastrointestinal tract carcinoids
      identified by routine colonoscopy with those identified as a result of symptoms.
      RESULTS: Twenty-eight (48.3%) incidentally identified carcinoids (15 small bowel
      and 13 large bowel) were compared with 30 (51.7%) symptomatic carcinoids.
      Incidental ileal carcinoids were similar in size (mean +/- SD, 1.3 +/- 0.61 vs
      1.7 +/- 1.13, p = 0.45) and incidence of lymph node metastases (12 in 15 vs 9 in
      15, p = 0.43) to symptomatic ileal carcinoids. However, incidental ileal
      carcinoids had a lower incidence of distant metastases (1 in 15 vs 7 in 15, p =
      0.035) compared with symptomatic ileal carcinoids. There was no difference in
      tumor size, extent of lymph node metastases, or distant metastases between
      incidental and symptomatic large bowel carcinoids. CONCLUSIONS: Ileal carcinoids
      identified at screening colonoscopy are associated with a significantly decreased
      incidence of distant metastases compared with those identified after development
      of symptoms, despite similar size and extent of lymph node metastases. However,
      incidental large bowel carcinoids appear to have similar staging to those
      identified as a result of symptoms.

PMID- 21880513
TI  - Ethical management of conflict of interest: proposed standards for academic
      surgical societies.
AB  - BACKGROUND: A significant increase in industry support of professional medical
      associations coupled with data suggesting that gifts from industry have
      significant clinical influence have prompted calls from the Institute of Medicine
      and physician leaders to identify and manage conflicts of interest that stem from
      financial support of professional medical associations by industry. STUDY DESIGN:
      A joint task force of members appointed by the Association for Academic Surgery
      and the Society of University Surgeons was convened in July 2009. Recommendations
      were developed regarding management of all potential conflicts of interest that
      can arise within the context of an academic surgical society, with specific focus
      on relationships with industry. Task force members reached consensus around each
      recommendation and the guidelines were subsequently adopted by the Executive
      Councils of both societies. RESULTS: The committee identified 4 primary areas of
      need for transparent and definitive management of conflict of interest: 1)
      individual society activities, including general budget support, society
      endorsements, and journal affiliation; 2) individual personnel conflicts such as
      society leadership and standards for disclosure of conflict; 3) meeting
      activities including budgetary support, program committee associations, and
      abstract review process; and 4) foundation support and research and travel
      awards. The resulting guidelines aim to protect the societies and their
      membership from undue bias that may undermine the credibility and mission of
      these associations. CONCLUSIONS: Policy guidelines to mitigate conflict of
      interest are necessary to protect the integrity of the work of academic surgical
      societies and their fiduciary duty to members and patients. Guidelines created
      and adopted by the Association for Academic Surgery and Society of University
      Surgeons form an effective model for academic surgical societies and their
      members.

PMID- 21880514
TI  - MicroRNA expression profiles in the progression of prostate cancer--from high
      grade prostate intraepithelial neoplasia to metastasis.
AB  - INTRODUCTION: Models of the multistep process related to cancer progression have
      been designed for many cancers including prostate. The aim of this study is to
      propose a new model including a possible role for recently described micro RNAs
      in prostate cancer (CaP) progression. METHODS: Sixty-three patients underwent
      radical prostatectomy to treat localized prostate carcinoma. The specimens of 15
      patients were representative of high grade prostate intraepithelial neoplasia
      (HGPIN). Fourteen specimens represented localized favorable CaP, and 34
      unfavorable, mostly non-organ-confined disease. Representing the advanced disease
      we studied 4 metastatic androgen-independent CaP and 2 cell lines. Micro RNAs
      were isolated using the mirVana miRNA Isolation kit and cDNA was obtained using
      the TaqMan miRNA Reverse Transcription kit to the miRNAs: hsa-miR-let7c, hsa-miR
      15a, hsa-miR-16, hsa-miR-21, hsa-miR-25, hsa-miR-32, hsa-miR-100, hsa-miR-143,
      hsa-miR-145, hsa-miR-146a, hsa-miR-191, hsa-miR-199a, hsa-miR-206, and hsa-miR
      218. Quantitative RT-PCR was carried out using the ABI 7500 Fast Real-Time PCR
      System and the TaqMan Universal PCR Master Mix. miRNA expression levels were
      measured by relative quantification, and fold expression changes were determined
      by the 2(-DeltaDeltaCT) method. The small nucleolar RNA RNU43 was used as an
      endogenous control. RESULTS: Except for miR-21 and miR-206, the expression levels
      of all miRNAs significantly changed during the progression of CaP. Interestingly,
      there was a significant global loss of miRNA expression between HGPIN and
      metastasis at 2 important steps. The first was related to the transition from
      HGPIN to invasive adenocarcinoma, and the second was related to the transition
      from localized to metastatic adenocarcinomas. CONCLUSION: Through the analysis of
      14 miRNAs in 4 groups of prostate lesions, which reproduced the progression of
      CaP, we showed that there is a global loss of miRNA expression at 2 distinct
      steps. The first related to the transition between HGPIN and localized invasive
      carcinoma, and the second associated with the transition from localized to
      metastatic CaP. The importance of our study is in the identification of possible
      miRNAs and miRNA-targeted genes involved in the progression of prostate
      carcinogenesis that may help the development of potential diagnostic or
      prognostic markers as well as the design of new target therapies.

PMID- 21880515
TI  - A systematic review of mid-term outcomes of thoracic endovascular repair (TEVAR)
      of chronic type B aortic dissection.
AB  - OBJECTIVE AND DESIGN: The role of Thoracic Endovascular Repair (TEVAR) in chronic
      type B aortic dissection remains controversial and its mid-term success as an
      alternative to open repair or best medical therapy remains unknown. The aim of
      the present study was to provide a systematic review of mid-term outcomes of
      TEVAR for chronic type B aortic dissection. MATERIALS AND METHODS: Medline, trial
      registries, conference proceedings and article reference lists from 1950 to
      January 2011 were searched to identify case series reporting mid-term outcomes of
      TEVAR in chronic type B dissection. Data were extracted for review. RESULTS: 17
      studies of 567 patients were reviewed. The technical success rate was 89.9%
      (range 77.6-100). Mid-term mortality was 9.2% (46/499) and survival ranged from
      59.1 to 100% in studies with a median follow-up of 24 months. 8.1% of patients
      (25/309) developed endoleak, predominantly type I. Re-intervention rates ranged
      from 0 to 60% in studies with a median follow-up of 31 months. 7.8% of patients
      (26/332) developed aneurysms of the distal aorta or continued false lumen
      perfusion with aneurysmal dilatation. Rare complications included delayed
      retrograde type A dissection (0.67%), aorto-oesophageal fistula (0.22%) and
      neurological complications (paraplegia 2/447, 0.45%; stroke 7/475, 1.5%).
      CONCLUSION: The absolute benefit of TEVAR over alternative treatments for chronic
      B-AD remains uncertain. The lack of natural history data for medically treated
      cases, significant heterogeneity in case selection and absence of consensus
      reporting standards for intervention are significant obstructions to interpreting
      the mid-term data. High-quality data from registries and clinical trials are
      required to address these challenges.

PMID- 21880516
TI  - The association between orthodontic treatment need and maxillary incisor trauma,
      a retrospective clinical study.
AB  - OBJECTIVES: Identifying risk factors for dental trauma in children is important.
      The main aim of this retrospective study was to investigate the association
      between maxillary incisor trauma (MIT) and variables such as gender, malocclusion
      complexity, and orthodontic treatment need (OTN). STUDY DESIGN: ICON (Index of
      Complexity, Outcome and Need) scores were calculated in 502 schoolchildren (253
      girls and 249 boys, aged 11-14-years). Subjects were categorized into 5 ICON
      complexity groups (easy to very difficult) and into 2 groups according to OTN
      (ICON >43, ICON <44). Logistic regression was performed to test for any
      differences in risk of MIT among subjects in different ICON complexity groups and
      to estimate the predictive value of gender, OTN, and ICON scores for MIT.
      RESULTS: Nine percent experienced incisor trauma (93.4% maxilla, 6.6% mandible).
      Enamel fracture was the most common type (6.2%) of dental trauma. Boys had
      greater odds of MIT compared with girls (odds ratio [OR] 2.16, 95% confidence
      interval [CI] 1.11-4.21). Subjects with OTN showed greater odds of MIT compared
      to those without (OR 2.37, 95% CI 1.21-4.64). Only subjects presenting with
      difficult complexity grade (64 < ICON < 77) showed significantly higher odds of
      experiencing MIT (OR 3.16, 95% CI 1.25-8.01) compared with the easy complexity
      group (ICON <29). CONCLUSION: The higher risk of experiencing MIT in
      malocclusions with difficult complexity warrants more vigilant screening of this
      group before and during dental or orthodontic treatment.

PMID- 21880517
TI  - Consideration of positioning errors in the assessment of distortion in the
      mandibular third molar region on panoramic radiographs.

PMID- 21880518
TI  - Uroporphyria in the Cyp1a2-/- mouse.
AB  - Cytochrome P4501A2 (Cyp1a2) is important in the development of uroporphyria in
      mice, a model of porphyria cutanea tarda in humans. Heretofore, mice homozygous
      for the Cyp1a2-/- mutation do not develop uroporphyria with treatment regimens
      that result in uroporphyria in wild-type mice. Here we report uroporphyria
      development in Cyp1a2-/- mice additionally null for both alleles of the
      hemochromatosis (Hfe) gene and heterozygous for deletion of the uroporphyrinogen
      decarboxylase (Urod) gene (genotype: Cyp1a2-/-;Hfe-/-;Urod+/-), demonstrating
      that upon adding porphyria-predisposing genetic manipulations, Cyp1a2 is not
      essential. Cyp1a2-/-;Hfe-/-;Urod+/- mice were treated with various combinations
      of an iron-enriched diet, parenteral iron-dextran, drinking water containing
      delta-aminolevulinic acid and intraperitoneal Aroclor 1254 (a polychlorinated
      biphenyl mixture) and analyzed for uroporphyrin accumulation. Animals fed an iron
      enriched diet alone did not develop uroporphyria but uroporphyria developed with
      all treatments that included iron supplementation and delta-aminolevulinic acid,
      even with a regimen without Aroclor 1254. Hepatic porphyrin levels correlated
      with low UROD activity and high levels of an inhibitor of UROD but marked
      variability in the magnitude of the porphyric response was present in all
      treatment groups. Gene expression profiling revealed no major differences between
      genetically identical triple cross mice exhibiting high and low magnitude
      porphyric responses from iron-enriched diet and iron-dextran supplementation, and
      delta-aminolevulinic acid. Even though the variation in porphyric response did
      not parallel the hepatic iron concentration, the results are compatible with the
      presence of a Cyp1a2-independent, iron-dependent pathway for the generation of
      uroporphomethene, the UROD inhibitor required for the expression of uroporphyria
      in mice and PCT in humans.

PMID- 21880519
TI  - Effect of particle size distribution and dietary crude fibre content on growth
      performance and gastric mucosa integrity of growing-finishing pigs.
AB  - This study was designed to examine the effect of crude fibre (CF) content and
      particle size of the diet on growth performance, carcass yield and gastric mucosa
      integrity. The experimental design was a 2*2 factorial trial with 192 pigs fed
      from 24 to 110 kg bodyweight. Four diets were compared: (1) low fibre finely
      ground; (2) low fibre coarsely ground; (3) high fibre finely ground; and (4) high
      fibre coarsely ground. All ingredients were ground before mixing. The high fibre
      coarsely ground diet resulted in the fewest lesions in the gastric pars
      oesophagea (P<0.001). Coarse grinding also resulted in the lowest urease activity
      in the stomach (P=0.006). The feed conversion ratio was worse on the coarsely
      ground diet than on the finely ground diet (P=0.038), whereas carcass yield was
      lower for pigs on the high fibre diet vs. the low fibre diet (P<0.001). Coarse
      grinding feed ingredients in a growing pig diet that is high in CF may reduce
      macroscopic lesions of the pars oesophagea but such a diet was accompanied in
      this study by inferior carcass yield.

PMID- 21880520
TI  - Dog obesity: keeping the weight off.

PMID- 21880523
TI  - Dramatic effect of vitamin D supplementation and a gluten-free diet on bone
      mineral density in a patient with celiac disease.

PMID- 21880522
TI  - HBonanza: a computer algorithm for molecular-dynamics-trajectory hydrogen-bond
      analysis.
AB  - In the current work, we present a hydrogen-bond analysis of 2673 ligand-receptor
      complexes that suggests the total number of hydrogen bonds formed between a
      ligand and its receptor is a poor predictor of ligand potency; furthermore, even
      that poor prediction does not suggest a statistically significant correlation
      between hydrogen-bond formation and potency. While we are not the first to
      suggest that hydrogen bonds on average do not generally contribute to ligand
      binding affinities, this additional evidence is nevertheless interesting. The
      primary role of hydrogen bonds may instead be to ensure specificity, to correctly
      position the ligand within the active site, and to hold the protein active site
      in a ligand-friendly conformation. We also present a new computer program called
      HBonanza (hydrogen-bond analyzer) that aids the analysis and visualization of
      hydrogen-bond networks. HBonanza, which can be used to analyze single structures
      or the many structures of a molecular dynamics trajectory, is open source and
      python implemented, making it easily editable, customizable, and platform
      independent. Unlike many other freely available hydrogen-bond analysis tools,
      HBonanza provides not only a text-based table describing the hydrogen-bond
      network, but also a Tcl script to facilitate visualization in VMD, a popular
      molecular visualization program. Visualization in other programs is also
      possible. A copy of HBonanza can be obtained free of charge from
      http://www.nbcr.net/hbonanza.

PMID- 21880524
TI  - Little evidence of low bone mass in acute lymphoblastic leukemia survivors.
AB  - Childhood acute lymphoblastic leukemia (ALL) survivors represent a specific group
      at risk for many health problems, including skeletal complications and
      osteoporosis. The objective of this study was to assess the risk of osteoporosis
      associated with the prevalence of low bone mass (according to the guidelines of
      the Pediatric Official Positions of the International Society for Clinical
      Densitometry 2007) in survivors of childhood ALL. The cross-sectional study was
      conducted in a cohort of 69 Caucasian children and adolescents (46 boys and 23
      girls) aged 12.15 +/- 0.5yr diagnosed with ALL and screened up to 5 yr after
      cessation of the treatment. Total body bone mineral content (TB BMC, g), total
      body bone mineral density (TB BMD, g/cm(2)), and lumbar spine BMD (LS BMD,
      g/cm(2)) were determined using dual-energy X-ray absorptiometry. Time interval
      from the completion of the treatment to the beginning of this study (subgroup I<2
      yr or subgroup II>2 yr after treatment), methotrexate (MTX) doses (subgroup I-MTX
      ranging from 0.5 to 1.0g/m(2); subgroup II-MTX>2.0 g/m(2)), cranial irradiation
      (subgroup I-without radiotherapy (RTX) and subgroup II receiving RTX of 12-18
      Gy), cumulative steroid dose, and impaired endocrine function were considered as
      potential factors affecting bone metabolism and included in the analysis. No
      differences were found in bone traits (BMC, TB BMD, LS BMD) in relation to
      examined risk factors. In multiple regression model that included therapeutical
      factors, a risk group and central nervous system irradiation were of an important
      influence on bone mass, and risk group predicted TB BMD in small degree. Risk
      group and irradiation status lost their significance after the inclusion of
      anthropometric, age-connected, and time-connected factors. This study suggests
      that ALL survivors are not at increased risk for low bone mass. However, from the
      clinical perspective all patients after childhood ALL should be screened for
      clinical signs, fracture history, and lifestyle risk factors for low bone mass
      and osteoporosis. They should be referred to bone density evaluation only as
      often as may be necessary from the clinical evaluation.

PMID- 21880526
TI  - Six novel mutations in the myophosphorylase gene in patients with McArdle disease
      and a family with pseudo-dominant inheritance pattern.
AB  - McArdle disease is an autosomal recessive glycogenosis due to deficiency of the
      enzyme myophosphorylase. It results from homozygous or compound heterozygous
      mutations in the gene for this enzyme, PYGM. We report six novel mutations in the
      PYGM gene based upon sequencing data including three missense mutations (p.D51G,
      p.P398L, and p.N648Y), one nonsense mutation (p.Y75X), one frame-shift mutation
      (p.Y114SfsX181), and one amino acid deletion (p.Y53del) in six patients with
      McArdle disease. We also report on a Caucasian family that appeared to transmit
      McArdle disease in an autosomal dominant manner. In order to evaluate the
      potential pathogenicity of the sequence variants, we performed in silico analysis
      using PolyPhen-2 and SIFT BLink, along with species conservation analysis using
      UCSC Genome Browser. The above mutations were all predicted to be disease
      associated with high probability and with at least the same level of certainty as
      several confirmed mutations. The current data add to the list of pathogenic
      mutations in the PYGM gene associated with McArdle disease.

PMID- 21880525
TI  - Clinical risk factors for fracture in diabetes: a matched cohort analysis.
AB  - The objective was to determine which individuals with diabetes are at increased
      risk for fracture. It is unknown whether traditional clinical risk factors (CRFs)
      can be used in this population to identify individuals at higher risk of
      fracture. Using the Manitoba Bone Density Program database, we identified 3054
      diabetic women and 9151 matched nondiabetic controls. The independent association
      of specific CRFs with incident osteoporotic fracture risk was assessed separately
      in those with diabetes and in controls, with subsequent examination of the
      interaction between diagnosed diabetes and each CRF. Prior major fractures were
      more prevalent in the diabetic group compared with the nondiabetic group (16.2%
      vs 14.3%, p<0.001). During mean 4 yr of observation, 259 (8.5%) of diabetic women
      and 559 (6.5%) of nondiabetic women experienced an incident major osteoporotic
      fracture (unadjusted hazard ratio [HR] for diabetes 1.49 [95% confidence interval
      (CI): 1.28-1.72], p<0.001; adjusted HR 1.14 [95% CI: 1.10-1.18], p<0.001). There
      were no significant differences between the 2 groups in the HRs for incident
      fracture associated with any of the CRFs studied (all p-for-interaction >0.1).
      Diabetes is a risk factor for major fracture. The ability of traditional CRFs to
      predict osteoporotic fractures is not influenced by the diagnosis of diabetes.

PMID- 21880527
TI  - Markers of feline leukaemia virus infection or exposure in cats from a region of
      low seroprevalence.
AB  - Molecular techniques have demonstrated that cats may harbour feline leukaemia
      virus (FeLV) provirus in the absence of antigenaemia. Using quantitative real
      time polymerase chain reaction (qPCR), p27 enzyme-linked immunosorbent assay
      (ELISA), anti-feline oncornavirus-associated cell-membrane-antigen (FOCMA)
      antibody testing and virus isolation (VI) we investigated three groups of cats.
      Among cats with cytopenias or lymphoma, 2/75 were transiently positive for
      provirus and anti-FOCMA antibodies were the only evidence of exposure in another.
      In 169 young, healthy cats, all tests were negative. In contrast, 3/4 cats from a
      closed household where FeLV was confirmed by isolation, had evidence of
      infection. Our results support a role for factors other than FeLV in the
      pathogenesis of cytopenias and lymphoma. There was no evidence of exposure in
      young cats. In regions of low prevalence, where the positive predictive value of
      antigen testing is low, qPCR may assist with diagnosis.

PMID- 21880528
TI  - Development of an injection site sarcoma shortly after meloxicam injection in an
      unvaccinated cat.
AB  - A single dose of a rapidly-absorbed non-steroidal anti-inflammatory drug (NSAID)
      was injected into the subcutaneous tissue of the interscapular region of a 12.5
      year-old cat. A mild swelling was noticed at the injection site 6 weeks later.
      This progressed into a 5 cm diameter mass which was removed 6 months after the
      injection had been given. An injection site sarcoma (ISS) was diagnosed
      histologically. As the cat had not been vaccinated for at least 12 years, the
      previous NSAID injection was considered to be a possible cause of the ISS.
      Inflammation is thought to be important in the development of ISS. If injection
      of a rapidly-absorbed NSAID can stimulate sufficient inflammation to promote the
      development of an ISS, other non-vaccine injections may also have the potential
      to influence ISS development. This suggests that injection of both vaccines and
      non-vaccine medications should be minimised to reduce the risk of ISS
      development.

PMID- 21880529
TI  - Locally invasive lymphangiosarcoma in a young domestic shorthair.
AB  - A 2-year-old, female spayed, domestic shorthair cat presented to the University
      of Missouri-Veterinary Medical Teaching Hospital (UMC-VMTH) with an approximately
      11-month history of fluid-draining pockets along her ventral thorax and axillae.
      The skin in these regions was erythematous, and multiple areas drained a serous
      to serosanguinous fluid. Fluid-filled, nodules formed along the ventrum, but
      these nodules disappeared as fluid drained spontaneously. Histologic assessment
      of skin biopsies revealed areas of vascular proliferation extending along the
      deep margin of the section and rare instances of invasion into the superficial
      dermis. These vascular channels were devoid of cells, lined by variably
      pleomorphic endothelial cells which had a low mitotic index. Based on the mild to
      moderate pleomorphism, positive staining with prospero-related homeobox gene-1
      (PROX-1), and the locally aggressive nature of the tumor, a final diagnosis of
      lymphangiosarcoma was made.

PMID- 21880530
TI  - Hematological abnormalities in HIV-infected patients.
AB  - BACKGROUND: Anemia, neutropenia, and thrombocytopenia are commonly observed in
      HIV-infected patients. This study was undertaken to evaluate the prevalence of
      cytopenias and their association with CD4 count. Furthermore, the association of
      hemoglobin concentration with mortality was also investigated. METHODS: We
      reviewed the data of 701 HIV-infected patients followed at our institution. Blood
      cell counts, hemoglobin concentration, CD4 count, and viral load were recorded.
      We also recorded the mortality rate after 1 year in the groups with CD4 <200/MUl
      and >= 200/MUl according to hemoglobin concentration. RESULTS: Of the total
      patients, 37.5% had anemia; 61.1% (110/180) were in the low CD4 group and 29.4%
      (153/521) were in the high CD4 group (p<0.01). Mean neutrophil counts were 2.610
      * 10(9)/l and 3.204 * 10(9)/l in the low CD4 and high CD4 groups, respectively
      (p<0.01); mean platelet counts were 218.639 * 10(9)/l and 234.807 * 10(9)/l for
      the low CD4 and the high CD4 groups, respectively (p=0.03). Patients whose
      hemoglobin concentration was below the median value had a higher death rate in
      both the low CD4 (14 vs. 4 deaths, p=0.013) and high CD4 (8 vs. 1 death,
      p=0.0158) groups. CONCLUSIONS: We found an association between CD4 count and
      hemoglobin level, neutrophil count, and platelet count, and that anemia was
      independently associated with a higher mortality.

PMID- 21880531
TI  - Tropheryma whipplei aortic valve endocarditis without systemic Whipple's disease.
AB  - Culture-negative endocarditis is most often the result of prior antimicrobial
      therapy. Tropheryma whipplei is the etiologic agent of Whipple's disease, which
      is typically characterized by diarrhea, weight loss, and intra-abdominal
      lymphadenopathy. We present the case of a 48-year-old male with Whipple's
      endocarditis of the aortic valve who did not develop signs of systemic Whipple's
      disease. Our patient was treated with a regimen that included ceftriaxone for 6
      weeks prior to his cardiac surgery, yet valve pathology demonstrated abundant T.
      whipplei, suggesting that a prolonged antibiotic course is necessary for the
      treatment of Whipple's endocarditis.

PMID- 21880532
TI  - Management and outcome of high-risk peritonitis: a retrospective survey 2005
      2009.
AB  - OBJECTIVES: To describe the clinical and microbiological aspects of high-risk
      peritonitis and to analyze their impact on its outcome. METHODS: This was a
      retrospective review of all culture-positive peritonitis between October 1, 2005
      and September 30, 2009. In accordance with recent Infectious Diseases Society of
      America (IDSA) guidelines, a group of high-risk peritonitis patients was selected
      based on age, severity of illness, underlying diseases, and acquisition of the
      infection. RESULTS: Ninety-three patients with high-risk peritonitis were
      studied; these patients were divided into subgroups of those with community
      associated disease (14%) and those with healthcare-associated disease (86%). The
      median age of patients was 66 (interquartile range (IQR) 22-95) years. The 30-day
      mortality rate was 25%. Subgroups differed in age (p=0.011), degree of
      comorbidity (p=0.023), severity of peritonitis (p=0.036), admission to the
      intensive care unit (ICU) (p=0.002), length of ICU stay (p<0.001), length of
      hospital stay (p<0.001), cure at day 30 (p=0.001), and adequate treatment
      (p=0.042). The microbiological etiology and resistance profiles were similar
      between the patient groups. Adequate empirical treatment was not related to a
      better outcome. Severity of disease (p=0.005) and the presence of enterococci
      (p=0.044) were independently associated with mortality. CONCLUSIONS: The mode of
      acquisition influences severity and certain parameters of outcome in high-risk
      peritonitis, but not its microbiological etiology. The outcome seems to depend
      primarily on severity of peritonitis and much less on the adequacy of treatment.

PMID- 21880533
TI  - [Target volume delineation for head and neck cancer intensity-modulated
      radiotherapy].
AB  - This article describes the determination and the delineation of the target
      volumes for head-and-neck cancers treated with intensity-modulated radiotherapy
      (IMRT). The delineation of the clinical target volumes (CTV) on the computerized
      tomography scanner (CT scan) requires a rigorous methodology due to the
      complexity of head-and-neck anatomy. The clinical examination with a sketch of
      pretreatment tumour extension, the surgical and pathological reports and the
      adequate images (CT scan, magnetic resonance imaging and fluorodeoxyglucose
      positron emission tomography) are necessary for the delineation. The target
      volumes depend on the overall strategy: sequential IMRT or simultaneous
      integrated boost-IMRT (SIB-IMRT). The concept of selectivity of the potential
      subclinical disease near the primary tumor and the selection of neck nodal
      targets are described according to the recommendations and the litterature. The
      planing target volume (PTV), mainly reflecting setup errors (random and
      systematic), results from a uniform 4-5mm expansion around the CTV. We propose
      the successive delineation of: (1) the gross volume tumour (GTV); (2) the "high
      risk" CTV1 around the GTV or including the postoperative tumour bed in case of
      positive margins or nodal extracapsular spread (65-70 Gy in 30-35 fractions); (3)
      the CTV2 "intermediate risk" around the CTV1 for SIB-IMRT (59-63 Gy in 30-35
      fractions); (4) the "low-risk" CTV3 (54-56 Gy in 30-35 fractions); (5) the PTVs.

PMID- 21880534
TI  - [Locally advanced cervical cancer: Should intensity-modulated radiotherapy
      replace brachytherapy?].
AB  - Intensity-modulated conformal radiotherapy (IMRT) is booming as treatment of
      locally advanced cervical cancer. This technique reduces the doses delivered to
      organs at risk and, by analogy to the irradiation of prostate cancer, opens the
      door to the possibility of dose escalation to levels close or similar to those
      achieved by brachytherapy. To date, several studies comparing IMRT with
      brachytherapy have been published, often methodologically flawed, concluding
      sometimes that both techniques are comparable. These results should be taken with
      extreme caution and should not overshadow the recent advances in brachytherapy
      with the use of 3D imaging and optimization. Preliminary works also showed that
      the combination of 3D optimized brachytherapy with IMRT could improve the
      management of the local disease especially for lesions poorly covered by
      intracavitary techniques.

PMID- 21880535
TI  - [Interest of FDG-PET for lung cancer radiotherapy].
AB  - The recent advances in medical imaging have profoundly altered the radiotherapy
      of non-small cell lung cancers (NSCLC). A meta-analysis has confirmed the
      superiority of FDG PET-CT over CT for initial staging. FDG PET-CT improves the
      reproducibility of target volume delineation, especially close to the mediastinum
      or in the presence of atelectasia. Although not formally validated by a
      randomized trial, the reduction of the mediastinal target volume, by restricting
      the irradiation to FDG-avid nodes, is widely accepted. The optimal method of
      delineation still remains to be defined. The role of FDG PET-CT in monitoring
      tumor response during radiotherapy is under investigation, potentially opening
      the way to adapting the treatment modalities to tumor radiation sensitivity.
      Other tracers, such as F-miso (hypoxia), are also under clinical investigation.
      To avoid excessive delays, the integration of PET-CT in routine practice requires
      quick access to the imaging equipment, technical support (fusion and image
      processing) and multidisciplinary delineation of target volumes.

PMID- 21880536
TI  - Tuning a lattice-Boltzmann model for applications in computational hemodynamics.
AB  - The interest in lattice-Boltzmann models in the computational hemodynamics realm
      has increased in recent years. In this context, the correct choice of numerical
      parameters for the appropriate simulation of blood flows in major arteries is a
      crucial aspect. For this reason, we present three parameter-tuning strategies
      that allow us to reproduce correctly the pulsatile time-dependent flow of an
      incompressible fluid under physiological regimes. These strategies are studied
      for a model based on a single-relaxation-time approach in combination with second
      order boundary conditions for both velocity and pressure, and proper equilibrium
      distributions that take care of the incompressible behavior exhibited by the
      fluid. The implementation is validated with the three-dimensional Womersley flow
      benchmark. As well, the simulation of blood flows in a curved artery, in an
      anastomosed vessel, in a patient specific vertebral artery and in an aneurysmal
      region are presented in order to show how the method and the setting of the
      numerical parameters are applied to different realistic hemodynamics problems.

PMID- 21880537
TI  - Relationships between disability, quality of life and prevalence of nonmotor
      symptoms in Parkinson's disease.
AB  - Patients with Parkinson's disease suffer from a variety of motor and nonmotor
      symptoms (NMS), report reduced quality of life and increased disability. Aims of
      this study are to assess the impact of Parkinson's disease on disability and
      quality of life, to evaluate the relationships between them and NMS prevalence.
      In this cross-sectional study, adult patients were consecutively enrolled and
      administered the World Health Organization Disability Assessment Schedule (WHO
      DAS II), the 36-Item Short-Form Health Survey (SF-36) and the Non Motor Symptoms
      Questionnaire (NMSQuest). One-sample t-test was used to compare WHO-DAS II and SF
      36 scores with normative value. Pearson's correlation was performed between
      NMSQuest, WHO-DAS II and SF-36 summary scales. Independent-sample t-test was used
      to compare NMSQuest, WHO-DAS II and SF-36 scores in patients with Hoehn & Yahr
      stage <3 and >= 3. In total, 96 patients were enrolled. SF-36 and WHO-DAS II
      scores were significantly worse than the normative values. Correlation
      coefficients between NMSQuest, WHO-DAS II and SF-36's mental score were moderate,
      and were high between WHO-DAS II and and SF-36's physical score. Patients with
      Hoehn & Yahr stage >= 3 reported reduced quality of life, higher disability and
      more NMS. Parkinson's disease severity is strongly associated with reduced
      quality of life, increased disability and NMS prevalence. Disability and quality
      of life assessment tools measure psychosocial facets that are similar
      specifically with regard to physical health component of health-related quality
      of life, are sensitive enough to capture differences related to disease's
      progression and increased prevalence of NMS.

PMID- 21880538
TI  - Clinical failure of botulinum toxin A in movement disorders.
AB  - OBJECTIVE: Botulinum toxin (BTX) injections have been used extensively in
      medicine; however, little is known about the factors predicting the loss of
      effectiveness of botulin toxin. METHODS: Using a clinical database, we identified
      401 subjects who had been treated for movement disorders from 1998 through 2010
      with onabotulinumtoxin A (BTX A) or who switched from BTX A to rimabotulinumtoxin
      B (BTX B). We compared patients who switched from type A to type B with patients
      using type A only with regard to number of visits, total number of injections,
      number of initial and final sites, number of initial units used, and duration of
      treatments. RESULTS: We observed that patients who switched from BTX A to B had a
      significantly higher number of initial injection sites than patients with BTX A
      only (BTX A to B median = 8.5; BTX A median = 6; p for difference = 0.006), had a
      higher number of final sites (BTX A to B median = 9 BTX A median = 7; p = 0.01),
      and were also more likely to have multiple reasons for injection (BTX A to B =
      25.0%; botulin toxin A = 5.3%; p = 0.01). We did not find significant differences
      between groups based on the other variables. CONCLUSIONS: Our findings suggest
      that higher number of sites rather than higher number of units or years of
      treatment are associated with the loss of effectiveness to BTX A. It is possible
      that the loss of effectiveness to the BTX is more strongly elicited when the
      injections are widely diffuse.

PMID- 21880539
TI  - Analytical techniques: surface and interfacial characterisation.

PMID- 21880540
TI  - Prognostic value of DNA ploidy status in patients with oral leukoplakia.
AB  - Oral leukoplakia is a potentially malignant disorder that will develop into oral
      cancer at an estimated rate of 1-2% per year. Aim of the present study is to
      assess the possible predictive value of DNA ploidy for malignant progression of
      oral leukoplakia. A cohort of 62 leukoplakia patients was studied and their
      biopsy was examined with standard histopathology and DNA image cytometry. Cox
      regression analysis was performed to establish the relationship between
      progression-free survival and the DNA ploidy status. During the follow-up time
      (median of 69 months) 13 patients developed an oral squamous cell carcinoma
      (OSCC). DNA aneuploidy was observed in 27 (44%) patients and was significantly
      associated with a shorter progression-free survival [Hazard ratio of 3.7, 95%
      confidence intervals (CI) of 1.1 and 13.0 and a p-value of 0.04]. Sensitivity and
      specificity scores were 54% and 60%, respectively. Aneuploidy was not correlated
      with dysplasia grading (chi-square analysis). DNA aneuploidy in oral leukoplakia
      is associated with an increased risk of progression to OSCC. However, for the
      individual leukoplakia patient, DNA ploidy status as single biomarker has limited
      value to predict progression to cancer.

PMID- 21880541
TI  - Determination for Enterobacter cloacae based on a europium ternary complex
      labeled DNA probe.
AB  - The fast detection and accurate diagnosis of the prevalent pathogenic bacteria is
      very important for the treatment of disease. Nowadays, fluorescence techniques
      are important tools for diagnosis. A two-probe tandem DNA hybridization assay was
      designed for the detection of Enterobacter cloacae based on time-resolved
      fluorescence. In this work, the authors synthesized a novel europium ternary
      complex Eu(TTA)(3)(5-NH(2)-phen) with intense luminescence, high fluorescence
      quantum yield and long lifetime before. We developed a method based on this
      europium complex for the specific detection of original extracted DNA from E.
      cloacae. In the hybridization assay format, the reporter probe was labeled with
      Eu(TTA)(3)(5-NH(2)-phen) on the 5'-terminus, and the capture probe capture probe
      was covalent immobilized on the surface of the glutaraldehyde treated glass
      slides. The original extracted DNA of samples was directly used without any DNA
      purification and amplification. The detection was conducted by monitoring the
      fluorescence intensity from the glass surface after DNA hybridization. The
      detection limit of the DNA was 5*10(-10) mol L(-1). The results of the present
      work proved that this new approach was easy to operate with high sensitivity and
      specificity. It could be conducted as a powerful tool for the detection of
      pathogen microorganisms in the environment.

PMID- 21880542
TI  - Growth and characterization of 2-amino-4-picolinium toluene sulfonate single
      crystal.
AB  - 2-Amino-4-picolinium toluene sulfonate (2A4PTS), a new organic material, was
      synthesized and grown as single crystals in room temperature by slow evaporation
      solution growth technique using water as solvent. The crystal structure of 2A4PTS
      has been determined using single crystal X-ray diffraction studies. 2A4PTS
      belongs to monoclinic crystal system. The molecular arrangements in the crystal
      were studied. The structural perfection of the grown crystals has been analysed
      by high-resolution X-ray diffraction (HRXRD) rocking curve measurements. Fourier
      transform infrared (FTIR) spectral studies have been performed to identify the
      functional groups. The optical transmittance window and the lower cutoff
      wavelength of the 2A4PTS have been identified by UV-Vis-NIR studies. The
      nonlinear optical properties have been investigated by Z-scan method. The
      nonlinear refractive index and linear absorption coefficient of the 2A4PTS are
      found to be in the order of 10(-8) cm(2)/W and 10(-4) cm/W, respectively. The
      laser induced surface damage threshold for the grown crystal was measured using
      Nd:YAG laser. Thermal analysis carried out on the compound reveals that 2A4PTS is
      stable up to 133 degrees C. The microhardness test was carried out and the load
      dependent hardness was measured.

PMID- 21880543
TI  - Disease burden of the most commonly detected respiratory viruses in hospitalized
      patients calculated using the disability adjusted life year (DALY) model.
AB  - BACKGROUND: The most common acute infections occur in the respiratory tract.
      Recent discoveries of several novel viruses have markedly increased the
      repertoire of agents understood to cause presentations of acute respiratory
      disease. OBJECTIVES: Further understanding is needed of the relative importance
      of newly discovered pathogens in the clinical setting to provide clinicians with
      an indication of appropriate diagnostic and therapeutic targets. To address this,
      quantification of the disease burden of respiratory viruses in hospitalized
      patients was undertaken. STUDY DESIGN: Disease burden caused by respiratory
      viruses in hospitalized patients was quantified using the World Health
      Organization endorsed DALY model. Diagnostic testing results from samples
      collected over three years for adenovirus (AdV), influenzas A and B,
      parainfluenza viruses 1, 2 and 3 (PIV-1, -2 and -3), respiratory syncytial virus
      (HRSV), and previously published retrospective screening for human
      metapneumovirus, rhinoviruses, and four respiratory coronaviruses were applied to
      the DALY model. Disability weights were calculated per 1000 hospitalized patients
      in age banded groups. RESULTS: Strikingly different disease burden profiles were
      observed in children and adults. Adenoviruses were among the leading cause of
      respiratory presentations in children but not adults. HRSV and influenza A were
      consistently one of the greatest causes of disease regardless of sampled
      population. Rhinoviruses and PIV-3 were significant pathogens in all groups
      except those aged 16-64 years. In immunocompromised patients rhinoviruses were
      the leading viral cause of disease. CONCLUSIONS: These analyses provide a
      framework which can be used to identify where finite resources should be directed
      in respiratory therapeutics and vaccine development.

PMID- 21880544
TI  - Low dosage promethazine and loratadine negatively affect neuromotor function.
AB  - OBJECTIVES: Determine how the sedating antihistamine promethazine and non
      sedating antihistamine loratadine at a dose of 10mg influence voluntary and
      involuntary motor processes in the hours following ingestion and the morning
      after ingestion. METHODS: Eight healthy young adults were recruited into a human
      double-blind, placebo-controlled, three-way crossover study. Neuromotor function
      was examined using a battery of controlled reaction time, postural tremor, and
      heart rate variability measures. Neuromotor function was assessed 4 times for
      each of the promethazine, loratadine and placebo interventions; pre-ingestion, 1h
      post-ingestion, 2h post-ingestion, and the following day. RESULTS: Self-perceived
      levels of drowsiness increased only after ingestion of promethazine. However,
      both antihistamines had negative effects on simple reaction time, choice reaction
      time, the RMS and peak power amplitude of postural tremor, and autonomic cardiac
      regulation. CONCLUSIONS: The presence of selective neuromotor deficits following
      ingestion of promethazine and loratadine suggest that sedating and non-sedating
      antihistamines alter neuromotor function. It is possible that the H(1)
      antagonists used in this study have antimuscarinic effects, which may impact on
      the central dopaminergic system that plays a role in modulating several CNS
      processes associated with movement. SIGNIFICANCE: Antihistamines are one of the
      most commonly procured over-the-counter medications. The current study suggests
      that taking non-sedating antihistamines to avoid the adverse drug reaction of
      drowsiness may not avoid unwanted motor control side-effects.

PMID- 21880545
TI  - A comparison of augmented low-Dye taping and ankle bracing on lower limb muscle
      activity during walking in adults with flat-arched foot posture.
AB  - OBJECTIVE: To compare the effect of taping and bracing on lower limb muscle
      activity during gait. DESIGN: Cross-sectional laboratory study. METHODS: Twenty
      seven asymptomatic adults with flat-arched foot posture were recruited to this
      study. They walked over-ground under three randomly allocated conditions: (i)
      barefoot; (ii) augmented low-Dye taping; (iii) replaceable ankle brace.
      Electromyographic (EMG) activity from tibialis posterior, tibialis anterior,
      peroneus longus and medial gastrocnemius was measured for each condition. Peak
      EMG amplitude and time of peak EMG amplitude were assessed from stance phase
      data. A series of one-way repeated measure analysis of variance followed by
      Bonferroni post hoc tests were undertaken (alpha=0.05). RESULTS: Tibialis
      posterior peak EMG amplitude decreased by 22% and 33% with bracing and taping
      (respectively), compared to barefoot. Peak amplitude was also decreased for
      peroneus longus by 34% and 30% and for tibialis anterior by 19% and 13% with
      bracing and taping (respectively), compared to barefoot. Small significant
      changes in time of peak EMG amplitude were found for tibialis posterior and
      tibialis anterior with taping and bracing compared to barefoot. The effect of
      taping and bracing was only different for tibialis posterior peak EMG amplitude,
      with tape producing a 15% reduction compared to bracing. CONCLUSION: The
      augmented low-Dye tape and replaceable ankle brace used in this study could be
      useful in managing overuse and dysfunction of selected leg muscles, particularly
      tibialis posterior, by reducing their level of activation during walking.

PMID- 21880546
TI  - MtbSD--a comprehensive structural database for Mycobacterium tuberculosis.
AB  - The Mycobacterium tuberculosis Structural Database (MtbSD)
      (http://bmi.icmr.org.in/mtbsd/MtbSD.php) is a relational database for the study
      of protein structures of M. tuberculosis. It currently holds information on
      description, reaction catalyzed and domains involved, active sites, structural
      homologues and similarities between bound and cognate ligands, for all the 857
      protein structures that are available for M. tb proteins. The database will be a
      valuable resource for TB researchers to select the appropriate protein-ligand
      complex of a given protein for molecular modelling, docking, virtual screening
      and structure-based drug designing.

PMID- 21880547
TI  - Congenital bladder diverticulum presenting as bladder outlet obstruction in
      infants and children.
AB  - PURPOSE: Congenital primary bladder diverticulum is a rare cause of infra-vesical
      obstruction. We present a series of 12 cases who presented with urinary retention
      secondary to a large primary bladder diverticulum. The aim is to high light the
      diagnostic difficulties and management issues of congenital bladder diverticulae.
      METHODS: We reviewed the case sheets of 12 patients with congenital bladder
      diverticulae who presented as lower tract obstruction with or without infection
      at a tertiary care centre in the last 10 years. All patients had urine
      examinations (complete microscopic with culture), serum creatinine,
      ultrasonography, intravenous urogram, voiding cystourethrogram with or without
      cystoscopy. The cases were managed by extravesical mobilization of diverticulae,
      diverticulectomy, and ureteric re-implantation. All patients (aged 1-36 months,
      mean 16.8 months) presented with retention of urine but 4 of them had symptoms of
      fever, tachycardia, abdominal distension and vomiting. Serum creatinine was
      normal in 10 out of 12 cases, but was high in two. Urine cultures grew
      Escherichia coli in 5 cases. Ultrasonography showed moderate to severe
      hydronephrosis on the left side in 5 cases, on the right side in 4 cases and
      bilateral in 3 cases but diverticulae could be located in only 8 cases.
      Intravenous urogram revealed hydrouretero-nephrosis in 9 cases, a poor
      functioning kidney with hydrouretero-nephrosis in 3 cases and bilateral
      hydrouretero-nephrosis in 3 cases. A Voiding Cystourethrogram confirmed the
      diagnosis in all cases. Vesicoureteric reflux (Grade 4-5) into the ipsilateral
      ureter was seen in 9 children of which it was bilateral in three cases. RESULTS:
      All children underwent extravesical diverticulectomy with re-implantation of the
      ipsilateral ureter in 9 cases, bilateral in 3 cases. All had an uneventful
      recovery except for one who had a suprapubic leak which healed on conservative
      treatment. Postoperative ultrasonograms showed mild hydronephrosis in 2 cases and
      micturating cystourethrograms revealed a grade III V-U reflux in one case which
      was managed conservatively. Patients are maintaining a sterile urine culture
      after a follow up of 6-36 months. CONCLUSION: Primary bladder diverticulum should
      be kept as a differential diagnosis in cases of bladder outlet obstruction in
      infants and children. A carefully done voiding cystourethrogram is the hallmark
      of diagnosis. Good results can be achieved by diverticulectomy and primary
      definitive repair with ureteric re-implantation even in infants.

PMID- 21880548
TI  - Ictal barking as a manifestation of temporal lobe epilepsy.
AB  - Ictal nonspeech vocalizations have been described as manifestations of either
      frontal or temporal epileptogenicity originating mainly from the dominant
      hemisphere. Ictal barking, particularly, has been considered a manifestation of
      mesial frontal epilepsy. A 42-year-old right-handed male with posttraumatic drug
      resistant complex partial epilepsy manifested ictal barking near electrographic
      onset. Extraoperative electrocorticography with subdural electrode coverage of
      the right frontoparietal and temporal and left frontal surfaces provided
      surveillance of ictal origin and propagation. Ictal origin was identified in the
      right mesial temporal lobe with barking vocalization manifesting within 3s of
      electrographic onset. No subsequent spread of activity was noted beyond the
      temporal lobe. Resection of the mesial temporal structure resulted in seizure
      freedom. Pathology identified hippocampal sclerosis. This case supports the
      notion that an intrinsic, intralobar epileptogenic neural network in either
      hemisphere can act as a conduit into the limbic and memory circuits without a
      laterality bias to manifest as barking.

PMID- 21880549
TI  - Risk of complications after bariatric surgery among individuals with and without
      type 2 diabetes mellitus.
AB  - BACKGROUND: Type 2 diabetes mellitus is highly prevalent in obese individuals.
      Bariatric surgery, promoted for reducing the medical problems of morbid obesity,
      has been increasingly recognized for its particular efficacy in treating
      diabetes. However, before bariatric surgery can be recommended for the treatment
      of diabetes, its safety in the diabetic population must be known. We assessed the
      odds of complications after bariatric surgery in patients with and without
      diabetes. METHODS: This was a retrospective cohort study. Using an administrative
      database from 7 Blue Cross/Blue Shield plans, we identified 22,288 subjects who
      had undergone bariatric surgery from 2002 to 2008. From this cohort, we selected
      6754 pairs of surgical patients (1 with and 1 without diabetes) matched by age,
      gender, health plan, and year of surgery. With conditional logistic regression
      analysis, we determined the relative odds of postoperative complications for <=
      12 months after surgery in the 2 groups. RESULTS: The mean age of the surgical
      patients was 46 years, and 79% were women. Postoperative complications were rare
      and comparable in those with and without diabetes. The most common complications
      were nausea, vomiting, and abdominal pain (8.8%), the need for a gastric revision
      procedure (5.0%), and upper endoscopy (2.3%). Select cardiac, infectious, and
      renal complications occurred more frequently in the diabetic group. The incidence
      of cardiac complications was greater in the 2-3-month and 4-6-month postoperative
      periods (odds ratio [OR] 1.7, P < .001), the incidence of infectious
      complications was greater in the 0-1-month (OR 1.3, P < .02) and 4-6-month (OR
      1.8, P < .001) periods, and the incidence of renal complications was greater in
      the 2-3-month postoperative period (OR 4.6, P = .01). CONCLUSIONS: Our findings
      support the safety of bariatric surgery in obese individuals with diabetes,
      although management strategies to avert postoperative cardiac, infectious, and
      renal complications in this population might be warranted.

PMID- 21880550
TI  - Band amiss in small bowel.

PMID- 21880551
TI  - The value prescription: relative value theorem as a call to action.
AB  - The Joint Commission of Pharmacy Practitioners Future Vision of Pharmacy Practice
      2015 (2005) and Project Destiny (2008) clearly defined a vision for transforming
      community practice pharmacy from a culture of dispensing drugs to the provision
      of services. Several viable service offerings were identified. Pharmacy has not
      yet fully capitalized on these opportunities. Pharmacy must demonstrate value in
      providing these services to remain viable in the marketplace. Many pharmacists do
      not understand how value is created and lack sufficient marketing skills to
      position their practice for long-term success. The relative value theorem (RVT)
      describes in simple terms the key elements that drive purchase decisions and thus
      marketing decisions: (P+S)*PV=RV (P, price; S, service; PV, perceived value; RV,
      relative value). A consumer compares the P, extra S, and PV of the purchase
      against all potential uses of their scarce resources before deciding what to buy.
      Evidence suggests that understanding and applying the principles of RVT is a
      critical skill for pharmacy professionals in all practice settings to master if
      they plan to remain viable players in the health care marketplace of the future.

PMID- 21880553
TI  - Sol-gel immobilized biosensor for the detection of organophosphorous pesticides:
      a voltammetric method.
AB  - Organophosphorous compounds are important neuroactive molecules whose presence
      exhibits significant analytical challenges. An acetylcholinesterase (AChE) based
      amperometric biosensor was developed by silica sol-gel film immobilization of the
      enzyme onto the carbon paste electrode. The mono enzyme biosensor was used for
      the determination of two organophosphorous compounds such as methyl parathion
      (MP) and acephate in 0.1M phosphate buffer (pH 7.0). The substrate used was
      acetylthiocholine chloride (ASChCl) confirmed the formation of thiocholine and it
      was electrochemically oxidized giving significant increase in anodic peak current
      around at 0.60 V versus calomel electrode. The influence of pH, enzyme loading
      and substrate concentration on the response of the biosensor was investigated.
      The monoenzyme biosensor provided linearity to methyl parathion and acephate in
      the concentration range of 0.1-0.5 ppb and 50-750 ppb with an incubation time of
      20 min and 4 min. The detection limits under the optimum working conditions were
      found to be 0.08 ppb for methyl parathion and 87 ppb for acephate. The sensor
      shows good operational stability 89% of its original activity for 60 successive
      measurements.

PMID- 21880554
TI  - A novel impedimetric nanobiosensor for low level determination of hydrogen
      peroxide based on biocatalysis of catalase.
AB  - A robust and effective nanocomposite film-glassy carbon modified electrode based
      on multi-walled carbon nanotubes and a room temperature ionic liquid 1-butyl-3
      methylimidazolium hexafluorophosphate was prepared by a layer-by-layer self
      assembly method. The fabricated modified electrode was used as a novel
      impedimetric catalase nanobiosensor for the determination of H(2)O(2). Direct
      electron transfer and electrocatalysis of catalase were fully investigated. The
      results suggested that catalase could be firmly adsorbed at the modified
      electrode. A pair of quasi-reversible redox peaks of catalase was observed in a
      0.20 M degassed phosphate buffer solution of pH 7.0. The nanocomposite film
      showed a pronounced increase in direct electron transfer between catalase and the
      electrode. The immobilized catalase exhibited an excellent electrocatalytic
      activity towards the reduction of H(2)O(2). The electrochemical impedance
      spectroscopy measurements revealed that the charge transfer resistance decreases
      significantly after enzymatic reaction with hydrogen peroxide, so that the
      prepared modified electrode can be used for the detection of ultra traces of
      H(2)O(2) (5-1700 nM).

PMID- 21880552
TI  - Neostigmine-induced contraction and nitric oxide-induced relaxation of isolated
      ileum from STZ diabetic guinea pigs.
AB  - Both delayed gastrointestinal transit and autonomic neuropathy have been
      documented in patients with diabetes mellitus. The mechanism of neostigmine, an
      agent that mimics release of acetylcholine from autonomic neurons by prokinetic
      agents, to contract smooth muscle, despite dysfunctional enteric neural pathways,
      was determined using isolated ilea from STZ-treated and control guinea pigs. Both
      bethanechol- and neostigmine-induced contractions were stronger in diabetic
      ileum. Bethanechol-induced contractions of control but not diabetic ileum were
      increased by low dose scopolamine suggesting reduced activation of presynaptic
      muscarinic autoreceptors in diabetic ileum. The muscarinic receptor antagonist 4
      DAMP strongly, but the nicotinic receptor antagonist hexamethonium only weakly,
      reduced neostigmine-induced contractions of control and diabetic ilea. The amount
      of acetylcholine, inferred from tissue choline content, was increased in diabetic
      ileum. Nicotinic neural and noncholinergic postjunctional smooth muscle receptors
      contributed more strongly to neostigmine-induced contractions in diabetic than
      control ileum. Relaxation of diabetic ileum by exogenous nitric oxide generated
      from sodium nitroprusside was comparable to control ileum, but smooth muscle
      relaxation by l-arginine using neuronal nitric oxide synthase to generate nitric
      oxide was weaker in diabetic ileum with evidence for a role for inducible nitric
      oxide synthase. Despite autonomic neuropathy, neostigmine strongly contracted
      ileum from diabetic animals but by a different mechanism including stronger
      activation of postjunctional muscarinic receptors, greater synaptic
      acetylcholine, stronger activation of noncholinergic excitatory pathways, and
      weaker activation of inhibitory pathways. A selective medication targeting a
      specific neural pathway may more effectively treat disordered gastrointestinal
      transit in patients with diabetes mellitus.

PMID- 21880556
TI  - Involvement of MRE11A and XPA gene polymorphisms in the modulation of DNA double
      strand break repair activity: a genotype-phenotype correlation study.
AB  - DNA double-strand breaks (DSB) are the most lethal form of ionizing radiation
      induced DNA damage, and failure to repair them results in cell death. In order to
      see if any associations exist between DNA repair gene polymorphisms and
      phenotypic profiles of DSB repair (DSBR) we performed a genotype-phenotype
      correlation study in 118 young healthy subjects (mean age 25.8+/-6.7years).
      Subjects were genotyped for 768 single nucleotide polymorphisms (SNPs) with a
      custom Illumina Golden Gate Assay, and an H2AX histone phosphorylation assay was
      done to test DSBR capacity. We found that H2AX phosphorylation at 1h was
      significantly lower in subjects heterozygous (no variant homozygotes were
      observed) for the XPA gene SNP rs3176683 (p-value=0.005), while dephosphorylation
      was significantly higher in subjects carrying the variant allele in three MRE11A
      gene SNPs: rs1014666, rs476137 and rs2508784 (p-value=0.003, 0.003 and 0.008,
      respectively). An additive effect of low-activity DNA repair alleles was
      associated with altered DSBR activity, as demonstrated by both H2AX
      phosphorylation at 1 h (p-trend <0.0001) and gammaH2AX dephosphorylation at 3h (p
      trend <0.0001). Our study revealed that in addition to SNPs of genes that are
      well-established players in DSBR, non-DSBR genes, such as the XPA gene that is
      mainly involved in the nucleotide excision repair pathway, can also influence
      DSBR in healthy subjects. This suggests that successful DSBR may require both
      DSBR and non-DSBR mechanisms.

PMID- 21880555
TI  - Processing of DNA structures via DNA unwinding and branch migration by the S.
      cerevisiae Mph1 protein.
AB  - The budding yeast Mph1 protein, the putative ortholog of human FANCM, possesses a
      3' to 5' DNA helicase activity and is capable of disrupting the D-loop structure
      to suppress chromosome arm crossovers in mitotic homologous recombination.
      Similar to FANCM, genetic studies have implicated Mph1 in DNA replication fork
      repair. Consistent with this genetic finding, we show here that Mph1 is able to
      mediate replication fork reversal, and to process the Holliday junction via DNA
      branch migration. Moreover, Mph1 unwinds 3' and 5' DNA Flap structures that bear
      key features of the D-loop. These biochemical results not only provide validation
      for a role of Mph1 in the repair of damaged replication forks, but they also
      offer mechanistic insights as to its ability to efficiently disrupt the D-loop
      intermediate.

PMID- 21880557
TI  - Determining the limits and confounders for the 2-pentyl furan breath test by gas
      chromatography/mass spectrometry.
AB  - Aspergillus fumigatus produces 2-pentyl furan (2-PF), a volatile compound not
      produced by many other pathogens or normal human metabolism. 2-Pentyl furan has
      been detected in the breath of patients with invasive aspergillosis (IA) by SPME
      pre-concentration coupled with CG/MS providing the possibility of an attractive
      diagnostic test. The limit of detection (LOD) and quantification (LOQ) for peak
      integration were assessed both statistically and empirically respectively. 2
      Pentyl furan was detected from 10 of 45 food stuffs tested. Levels were highest
      from soymilk (3 of 3 brands), lower from pumpkin, peanuts, rolled oats 2, Ensure
      Plus, tinned asparagus, tinned beans and a vegetable exact (Marmite). No 2-PF was
      detectable in anti-fungal medications used to treat IA or commonly used cosmetics
      tested. There was no difference in 2-PF breath levels between morning and
      afternoon or fasting and non fasting samples taken from healthy subjects eating a
      diet without 2-PF rich foods. 2-Pentyl furan levels were present in breath
      samples immediately after a mouth rinse with soy milk (P<0.001), and in some
      subjects after ingesting soy milk and rinsing their mouth with water. The breath
      test for 2-PF can be conducted without an overnight fast or at a specified time
      provided the mouth has been rinsed 30 min or more from when 2-PF containing
      products have been ingested.

PMID- 21880558
TI  - Universality of design and its evolution: comment on "The constructal law and the
      evolution of design in nature".

PMID- 21880559
TI  - Knock-down of SOX11 induces autotaxin-dependent increase in proliferation in
      vitro and more aggressive tumors in vivo.
AB  - The transcription factor SOX11 is a novel diagnostic marker for mantle cell
      lymphoma (MCL), distinguishing this aggressive tumor from potential simulators.
      Recent data also show that the level of SOX11 correlates to in vitro growth
      properties in MCL, as well as the clinical progression. We have previously shown
      that MCL-associated pathways, such as Rb-E2F, are dysregulated leading to
      decreased proliferation upon overexpression of SOX11, emphasizing the impact of
      SOX11 on MCL-specific gene expression and growth control. However, it remains to
      be determined which growth regulatory pathways that are induced upon SOX11 knock
      down, leading to an increased cellular growth. Consequently, we established a
      model cell line with constitutive down-regulation of SOX11. The highly
      proliferative features of this cell line were investigated by gene expression
      analysis, proliferation assay, cell cycle distribution and potential to induce
      tumors in NOD-SCID mice. Our in vitro studies demonstrated a SOX11-dependent
      regulation of MCL-specific gene expression. In addition, we identified autotaxin
      (ATX) to be regulated by SOX11. Our results clearly showed a correlation between
      SOX11 level and cellular growth rate, which was dependent on ATX, as well as a
      direct relation between the level of SOX11 in tumorigenic cells and the growth
      rate of these tumors in NOD-SCID mice.

PMID- 21880560
TI  - Hepatitis E virus infection as a cause of acute hepatitis in Southern Italy.
AB  - BACKGROUND: Hepatitis E virus (HEV) is a major cause of acute hepatitis in
      developing countries, whereas it is not considered a major health problem in
      Western World. AIMS: To investigate the spread of HEV and its possible role in
      causing acute hepatitis in Southern Italy. METHODS: Four hundred and thirty
      patients observed from April to December 2009 were studied and grouped as
      follows: 55 individuals with acute hepatitis (AH), 33 of whom cryptogenic; 321
      individuals with chronic liver diseases (CLD), (278 Italians and 43 immigrants);
      54 individuals without liver disease (control-group). Serum samples from all
      cases were tested for IgG anti-HEV antibodies and those positive to this test as
      well as all AH cases were also tested both for IgM anti-HEV and HEV RNA. RESULTS:
      Two of 33 (6%) cryptogenic AH cases were associated with HEV infection as shown
      by positive IgM anti-HEV test. Both these patients had not travelled to areas at
      high HEV endemicity. HEV RNA was not found in any sample tested. IgG anti-HEV
      antibodies were detected in 5.7% of Italians with CLD and 3.7% of the control
      group. No immigrant was found positive for any HEV marker. CONCLUSION:
      Autochthonous HEV infection is present in Southern Italy where it may cause AH.

PMID- 21880561
TI  - Coeliac disease characteristics, compliance to a gluten free diet and risk of
      lymphoma by subtype.
AB  - OBJECTIVE: Coeliac disease is associated with an increased risk of malignant
      lymphomas. We investigated the importance of coeliac disease characteristics and
      diet compliance for risk of lymphoma. METHODS: In a nested case-control design,
      we identified 59 patients with lymphoma and 137 matched controls from a
      population-based cohort of 11,650 inpatients with coeliac disease. We assessed
      coeliac disease characteristics at diagnosis and dietary compliance collected
      prospectively from medical records during follow-up. RESULTS: Poor compliance was
      not significantly associated with risk of lymphoma overall (odds ratio 1.83, 95%
      confidence interval 0.78-4.31) nor of lymphoma subtypes. Risk estimates differed
      by subtype; risk of T-cell lymphoma (odds ratio 1.01, confidence interval 0.32
      3.15) or intestinal lymphoma (odds ratio 0.66, confidence interval 0.17-2.56) was
      unelevated, whereas there was an indication of a risk increase of B-cell lymphoma
      (odds ratio 4.74, confidence interval 0.89-25.3) or extraintestinal lymphoma
      (odds ratio 3.00, confidence interval 0.73-12.3) following poor compliance.
      History of weight loss (odds ratio 2.89, confidence interval 1.00-8.29) at
      coeliac disease diagnosis was associated with an increased risk of lymphoma when
      excluding tumours occurring with short latency (<3 years). CONCLUSIONS:
      Compliance to a gluten-free diet did not significantly alter lymphoma risk, but a
      moderate effect cannot be excluded. Weight loss, a potential marker of coeliac
      disease severity, may be associated with lymphoma risk.

PMID- 21880562
TI  - The effect of viewing ultra-fit images on college women's body dissatisfaction.
AB  - Modern ideals of female attractiveness include an extremely toned and fit
      appearance in addition to extreme thinness. Although viewing thin models has a
      negative effect on women's body image, research has not tested the effect of
      exposure to the ultra-fit physique separate from the thin-ideal. This randomized,
      posttest-only experiment tested the effects of the athletic aspect of the current
      ideal by exposing 138 undergraduate women to thin and athletic models, normal
      weight athletic models, or a control condition consisting of neutral objects. The
      study also tested the moderating effects of thin-ideal and athletic-ideal
      internalization. Exposure to thin ultra-fit models, but not normal weight ultra
      fit models, produced an increase in body dissatisfaction and neither
      internalization variable moderated this effect. Findings suggest that
      interventions that focus on the benefits of fitness while challenging the
      desirability of thinness may offer promising results.

PMID- 21880563
TI  - Is Asian ethnicity an independent risk factor for severe perineal trauma in
      childbirth? A systematic review of the literature.
AB  - OBJECTIVE: To undertake a systematic review of the literature to determine
      whether Asian ethnicity is an independent risk factor for severe perineal trauma
      in childbirth. METHOD: Ovid Medline, CINAHL, and Cochrane databases published in
      English were used to identify appropriate research articles from 2000 to 2010,
      using relevant terms in a variety of combinations. All articles included in this
      systematic review were assessed using the Critical Appraisal Skills Programme
      (CASP) 'making sense of evidence' tools. FINDINGS: Asian ethnicity does not
      appear to be a risk factor for severe perineal trauma for women living in Asia.
      In contrast, studies conducted in some Western countries have identified Asian
      ethnicity as a risk factor for severe perineal trauma. It is unknown why (in some
      situations) Asian women are more vulnerable to this birth complication. The lack
      of an international standard definition for the term Asian further undermines
      clarification of this issue. Nevertheless, there is an urgent need to explore why
      Asian women are reported to be significantly at risk for severe perineal trauma
      in some Western countries. CONCLUSION: Current research on this topic is
      confusing and conflicting. Further research is urgently required to explore why
      Asian women are at risk for severe perineal trauma in some birth settings.

PMID- 21880564
TI  - Botanical DNA evidence in criminal cases: Knotgrass (Polygonum aviculare L.) as a
      model species.
AB  - The possibilities and strategies for using DNA characteristics to link a
      botanical sample to a specific source plant or location vary with its breeding
      system. For inbreeding species, which often form small patches of identical
      genotypes, knotgrass (Polygonum aviculare L.) is a suitable model species because
      of its (1) occurrence in a wide range of natural environments, (2) abundant
      presence in pieces of evidence, and (3) ease in molecular processing. The value
      of knotgrass for forensic casework was demonstrated using data from a homicide
      case. Using the DNA fingerprinting technique AFLP((r)) we were able to identify
      the knotgrass population at the crime site as the most likely origin of the
      botanical evidence. We expect that the development of tailored marker systems for
      knotgrass and other frequently occurring (model) species will considerably
      accelerate the use of botanical DNA evidence in criminal cases.

PMID- 21880565
TI  - A statistical model for quantification and prediction of cardiac remodelling:
      application to tetralogy of Fallot.
AB  - Cardiac remodelling plays a crucial role in heart diseases. Analyzing how the
      heart grows and remodels over time can provide precious insights into
      pathological mechanisms, eventually resulting in quantitative metrics for disease
      evaluation and therapy planning. This study aims to quantify the regional impacts
      of valve regurgitation and heart growth upon the end-diastolic right ventricle
      (RV) in patients with tetralogy of Fallot, a severe congenital heart defect. The
      ultimate goal is to determine, among clinical variables, predictors for the RV
      shape from which a statistical model that predicts RV remodelling is built. Our
      approach relies on a forward model based on currents and a diffeomorphic surface
      registration algorithm to estimate an unbiased template. Local effects of RV
      regurgitation upon the RV shape were assessed with Principal Component Analysis
      (PCA) and cross-sectional multivariate design. A generative 3-D model of RV
      growth was then estimated using partial least squares (PLS) and canonical
      correlation analysis (CCA). Applied on a retrospective population of 49 patients,
      cross-effects between growth and pathology could be identified. Qualitatively,
      the statistical findings were found realistic by cardiologists. 10-fold cross
      validation demonstrated a promising generalization and stability of the growth
      model. Compared to PCA regression, PLS was more compact, more precise and
      provided better predictions.

PMID- 21880566
TI  - Robust brain extraction across datasets and comparison with publicly available
      methods.
AB  - Automatic whole-brain extraction from magnetic resonance images (MRI), also known
      as skull stripping, is a key component in most neuroimage pipelines. As the first
      element in the chain, its robustness is critical for the overall performance of
      the system. Many skull stripping methods have been proposed, but the problem is
      not considered to be completely solved yet. Many systems in the literature have
      good performance on certain datasets (mostly the datasets they were trained/tuned
      on), but fail to produce satisfactory results when the acquisition conditions or
      study populations are different. In this paper we introduce a robust, learning
      based brain extraction system (ROBEX). The method combines a discriminative and a
      generative model to achieve the final result. The discriminative model is a
      Random Forest classifier trained to detect the brain boundary; the generative
      model is a point distribution model that ensures that the result is plausible.
      When a new image is presented to the system, the generative model is explored to
      find the contour with highest likelihood according to the discriminative model.
      Because the target shape is in general not perfectly represented by the
      generative model, the contour is refined using graph cuts to obtain the final
      segmentation. Both models were trained using 92 scans from a proprietary dataset
      but they achieve a high degree of robustness on a variety of other datasets.
      ROBEX was compared with six other popular, publicly available methods (BET, BSE,
      FreeSurfer, AFNI, BridgeBurner, and GCUT) on three publicly available datasets
      (IBSR, LPBA40, and OASIS, 137 scans in total) that include a wide range of
      acquisition hardware and a highly variable population (different age groups,
      healthy/diseased). The results show that ROBEX provides significantly improved
      performance measures for almost every method/dataset combination.

PMID- 21880567
TI  - Hierarchical parameter identification in models of respiratory mechanics.
AB  - Potential harmful effects of ventilation therapy could be reduced by model-based
      predictions of the effects of ventilator settings to the patient. To obtain
      optimal predictions, the model has to be individualized based on patients' data.
      Given a nonlinear model, the result of parameter identification using iterative
      numerical methods depends on initial estimates. In this work, a feasible
      hierarchical identification process is proposed and compared to the commonly
      implemented direct approach with randomized initial values. The hierarchical
      approach is exemplarily illustrated by identifying the viscoelastic model (VEM)
      of respiratory mechanics, whose a priori identifiability was proven. To
      demonstrate its advantages over the direct approach, two different data sources
      were employed. First, correctness of the approach was shown with simulation data
      providing controllable conditions. Second, the clinical potential was evaluated
      under realistic conditions using clinical data from 13 acute respiratory distress
      syndrome (ARDS) patients. Simulation data revealed that the success rate of the
      direct approach exponentially decreases with increasing deviation of the initial
      estimates while the hierarchical approach always obtained the correct solution.
      The average computing time using clinical data for the direct approach equals
      4.77 s (SD  =  1.32) and 2.41 s (SD  =  0.01) for the hierarchical approach.
      These investigations demonstrate that a hierarchical approach may be beneficial
      with respect to robustness and efficiency using simulated and clinical data.

PMID- 21880568
TI  - Automatic anterior chamber angle assessment for HD-OCT images.
AB  - Angle-closure glaucoma is a major blinding eye disease and could be detected by
      measuring the anterior chamber angle in the human eyes. High-definition OCT
      (Cirrus HD-OCT) is an emerging noninvasive, high-speed, and high-resolution
      imaging modality for the anterior segment of the eye. Here, we propose a novel
      algorithm which automatically detects a new landmark, Schwalbe's line, and
      measures the anterior chamber angle in the HD-OCT images. The distortion caused
      by refraction is corrected by dewarping the HD-OCT images, and three biometric
      measurements are defined to quantitatively assess the anterior chamber angle. The
      proposed algorithm was tested on 40 HD-OCT images of the eye and provided
      accurate measurements in about 1 second.

PMID- 21880569
TI  - Neural networks-based adaptive control for nonlinear time-varying delays systems
      with unknown control direction.
AB  - This paper investigates a neural network (NN) state observer-based adaptive
      control for a class of time-varying delays nonlinear systems with unknown control
      direction. An adaptive neural memoryless observer, in which the knowledge of time
      delay is not used, is designed to estimate the system states. Furthermore, by
      applying the property of the function tanh(2)(theta/epsilon)/theta (the function
      can be defined at theta = 0) and introducing a novel type appropriate Lyapunov
      Krasovskii functional, an adaptive output feedback controller is constructed via
      backstepping method which can efficiently avoid the problem of controller
      singularity and compensate for the time-delay. It is highly proven that the
      closed-loop systems controller designed by the NN-basis function property, new
      kind parameter adaptive law and Nussbaum function in detecting the control
      direction is able to guarantee the semi-global uniform ultimate boundedness of
      all signals and the tracking error can converge to a small neighborhood of zero.
      The characteristic of the proposed approach is that it relaxes any restrictive
      assumptions of Lipschitz condition for the unknown nonlinear continuous
      functions. And the proposed scheme is suitable for the systems with mismatching
      conditions and unmeasurable states. Finally, two simulation examples are given to
      illustrate the effectiveness and applicability of the proposed approach.

PMID- 21880570
TI  - Nonlinear regularization path for quadratic loss support vector machines.
AB  - Regularization path algorithms have been proposed to deal with model selection
      problem in several machine learning approaches. These algorithms allow
      computation of the entire path of solutions for every value of regularization
      parameter using the fact that their solution paths have piecewise linear form. In
      this paper, we extend the applicability of regularization path algorithm to a
      class of learning machines that have quadratic loss and quadratic penalty term.
      This class contains several important learning machines such as squared hinge
      loss support vector machine (SVM) and modified Huber loss SVM. We first show that
      the solution paths of this class of learning machines have piecewise nonlinear
      form, and piecewise segments between two breakpoints are characterized by a class
      of rational functions. Then we develop an algorithm that can efficiently follow
      the piecewise nonlinear path by solving these rational equations. To solve these
      rational equations, we use rational approximation technique with quadratic
      convergence rate, and thus, our algorithm can follow the nonlinear path much more
      precisely than existing approaches such as predictor-corrector type nonlinear
      path approximation. We show the algorithm performance on some artificial and real
      data sets.

PMID- 21880571
TI  - Object segmentation of database images by dual multiscale morphological
      reconstructions and retrieval applications.
AB  - Processing images for specific targets on a large scale has to handle various
      kinds of contents with regular processing steps. To segment objects in one image,
      we utilized dual multiScalE Graylevel mOrphological open and close
      recoNstructions (SEGON) to build a background (BG) gray-level variation mesh,
      which can help to identify BG and object regions. It was developed from a
      macroscopic perspective on image BG gray levels and implemented using standard
      procedures, thus robustly dealing with large-scale database images. The image
      segmentation capability of existing methods can be exploited by the BG mesh to
      improve object segmentation accuracy. To evaluate the segmentation accuracy, the
      probability of coherent segmentation labeling, i.e., the normalized probability
      random index (PRI), between a computer-segmented image and the hand-labeled one
      is computed for comparisons. Content-based image retrieval (CBIR) was carried out
      to evaluate the object segmentation capability in dealing with large-scale
      database images. Retrieval precision-recall (PR) and rank performances, with and
      without SEGON, were compared. For multi-instance retrieval with shape feature,
      AdaBoost was used to select salient common feature elements. For color features,
      the histogram intersection between two scalable HSV descriptors was calculated,
      and the mean feature vector was used for multi-instance retrieval. The distance
      measure for color feature can be adapted when both positive and negative queries
      are provided. The normalized correlation coefficient of features among query
      samples was computed to integrate the similarity ranks of different features in
      order to perform multi-instance with multifeature query. Experiments showed that
      the proposed object segmentation method outperforms others by 21% in the PRI.
      Performing SEGON-enabled CBIR on large-scale databases also improves on the PR
      performance reported elsewhere by up to 42% at a recall rate of 0.5. The proposed
      object segmentation method can be extended to extract other image features, and
      new feature types can be incorporated into the algorithm to further improve the
      image retrieval performance.

PMID- 21880572
TI  - Enhancing collaborative filtering by user interest expansion via personalized
      ranking.
AB  - Recommender systems suggest a few items from many possible choices to the users
      by understanding their past behaviors. In these systems, the user behaviors are
      influenced by the hidden interests of the users. Learning to leverage the
      information about user interests is often critical for making better
      recommendations. However, existing collaborative-filtering-based recommender
      systems are usually focused on exploiting the information about the user's
      interaction with the systems; the information about latent user interests is
      largely underexplored. To that end, inspired by the topic models, in this paper,
      we propose a novel collaborative-filtering-based recommender system by user
      interest expansion via personalized ranking, named iExpand. The goal is to build
      an item-oriented model-based collaborative-filtering framework. The iExpand
      method introduces a three-layer, user-interests-item, representation scheme,
      which leads to more accurate ranking recommendation results with less computation
      cost and helps the understanding of the interactions among users, items, and user
      interests. Moreover, iExpand strategically deals with many issues that exist in
      traditional collaborative-filtering approaches, such as the overspecialization
      problem and the cold-start problem. Finally, we evaluate iExpand on three
      benchmark data sets, and experimental results show that iExpand can lead to
      better ranking performance than state-of-the-art methods with a significant
      margin.

PMID- 21880573
TI  - Developing learning algorithms via optimized discretization of continuous
      dynamical systems.
AB  - Most of the existing numerical optimization methods are based upon a
      discretization of some ordinary differential equations. In order to solve some
      convex and smooth optimization problems coming from machine learning, in this
      paper, we develop efficient batch and online algorithms based on a new principle,
      i.e., the optimized discretization of continuous dynamical systems (ODCDSs).
      First, a batch learning projected gradient dynamical system with Lyapunov's
      stability and monotonic property is introduced, and its dynamical behavior
      guarantees the accuracy of discretization-based optimizer and applicability of
      line search strategy. Furthermore, under fair assumptions, a new online learning
      algorithm achieving regret  O(?T) or  O(logT) is obtained. By using the line
      search strategy, the proposed batch learning ODCDS exhibits insensitivity to the
      step sizes and faster decrease. With only a small number of line search steps,
      the proposed stochastic algorithm shows sufficient stability and approximate
      optimality. Experimental results demonstrate the correctness of our theoretical
      analysis and efficiency of our algorithms.

PMID- 21880574
TI  - Prevalence and Global Health implications of social media in direct-to-consumer
      drug advertising.
AB  - BACKGROUND: Direct-to-consumer advertising (DTCA), linked to inappropriate
      medication use and higher health care expenditures, is the fastest growing form
      of pharmaceutical marketing. DTCA is legal only in the United States and New
      Zealand. However, the advent of online interactive social media "Web 2.0"
      technologies-that is, eDTCA 2.0-may circumvent DTCA legal proscriptions.
      OBJECTIVE: The purpose of this study was to assess the prevalence of DTCA of
      leading pharmaceutical company presence and drug product marketing in online
      interactive social media technologies (eDTCA 2.0). METHODS: We conducted a
      descriptive study of the prevalence of eDTCA 2.0 marketing in the top 10 global
      pharmaceutical corporations and 10 highest grossing drugs of 2009. RESULTS: All
      pharmaceutical companies reviewed (10/10, 100%) have a presence in eDTCA 2.0 on
      Facebook, Twitter/Friendster, sponsored blogs, and really simple syndication
      (RSS) feeds. In addition, 80% (8/10) have dedicated YouTube channels, and 80%
      (8/10) developed health care communication-related mobile applications. For
      reviewed drugs, 90% (9/10) have dedicated websites, 70% (7/10) have dedicated
      Facebook pages, 90% (9/10) have health communications-related Twitter and
      Friendster traffic, and 80% (8/10) have DTCA television advertisements on
      YouTube. We also found 90% (9/10) of these drugs had a non-corporate eDTCA 2.0
      marketing presence by illegal online drug sellers. CONCLUSION: Pharmaceutical
      companies use eDTCA 2.0 to market themselves and their top-selling drugs. eDTCA
      2.0 is also used by illicit online drug sellers. Regulators worldwide must take
      into account the current eDTCA 2.0 presence when attempting to reach policy and
      safety goals.

PMID- 21880576
TI  - The yield of 18F-FDG PET/CT in patients with clinical stage IIA, IIB, or IIIA
      breast cancer: a prospective study.
AB  - The purpose of this study was to prospectively evaluate the role of (18)F-FDG
      PET/CT in patients with stage IIA, IIB, or IIIA breast cancer. METHODS: During 56
      mo, 131 consecutive patients with large (>2 cm) breast cancer and clinical stage
      IIA, IIB, or IIIA (based on clinical examination, mammography, breast MRI, and
      ultrasonography) underwent (18)F-FDG PET/CT. The nuclear physician was unaware of
      the results of any other procedure (bone scan, chest radiography, liver
      ultrasound, or thoracoabdominal CT scan). RESULTS: Of the 131 examined patients,
      36 had clinical stage IIA (34 T2N0 and 2 T1N1), 48 stage IIB (20 T3N0 and 28
      T2N1), and 47 stage IIIA (29 T3N1, 9 T2N2, and 9 T3N2). (18)F-FDG PET/CT modified
      staging for 5.6% of stage IIA patients, for 14.6% of stage IIB patients, and for
      27.6% of stage IIIA patients. However, within stage IIIA, the yield was
      specifically high among the 18 patients with N2 disease (56% stage modification).
      When considering stage IIB and primary operable IIIA (T3N1) together, the yield
      of (18)F-FDG PET/CT was 13% (10/77); extraaxillary regional lymph nodes were
      detected in 5 and distant metastases in 7 patients. In this series, (18)F-FDG
      PET/CT outperformed bone scanning, with only 1 misclassification versus 8 for
      bone scanning (P = 0.036). CONCLUSION: (18)F-FDG PET/CT provided useful
      information in 13% of patients with clinical T3N0, T2N1, or T3N1 disease. The
      yield was more modest in patients with stage IIA. The high yield in the case of
      N2 disease demonstrates that stage IIIA comprises 2 quite distinct groups of
      patients.

PMID- 21880575
TI  - Brain and whole-body imaging in rhesus monkeys of 11C-NOP-1A, a promising PET
      radioligand for nociceptin/orphanin FQ peptide receptors.
AB  - Our laboratory developed (S)-3-(2'-fluoro-6',7'-dihydrospiro[piperidine-4,4'
      thieno[3,2-c]pyran]-1-yl)-2-(2-fluorobenzyl)-N-methylpropanamide ((11)C-NOP-1A),
      a new radioligand for the nociceptin/orphanin FQ peptide (NOP) receptor, with
      high affinity (K(i), 0.15 nM) and appropriate lipophilicity (measured logD, 3.4)
      for PET brain imaging. Here, we assessed the utility of (11)C-NOP-1A for
      quantifying NOP receptors in the monkey brain and estimated the radiation safety
      profile of this radioligand based on its biodistribution in monkeys. METHODS:
      Baseline and blocking PET scans were acquired from head to thigh for 3 rhesus
      monkeys for approximately 120 min after (11)C-NOP-1A injection. These 6 PET scans
      were used to quantify NOP receptors in the brain and to estimate radiation
      exposure to organs of the body. In the blocked scans, a selective nonradioactive
      NOP receptor antagonist (SB-612111; 1 mg/kg intravenously) was administered
      before (11)C-NOP-1A. In all scans, arterial blood was sampled to measure the
      parent radioligand (11)C-NOP-1A. Distribution volume (V(T); a measure of receptor
      density) was calculated with a compartment model using brain and arterial plasma
      data. Radiation-absorbed doses were calculated using the MIRD Committee scheme.
      RESULTS: After (11)C-NOP-1A injection, peak uptake of radioactivity in the brain
      had a high concentration (~5 standardized uptake value), occurred early (~12
      min), and thereafter washed out quickly. V(T) (mL . cm(-3)) was highest in the
      neocortex (~20) and lowest in hypothalamus and cerebellum (~13). SB-612111
      blocked approximately 50%-70% of uptake and reduced V(T) in all brain regions to
      approximately 7 mL . cm(-3). Distribution was well identified within 60 min of
      injection and stable for the remaining 60 min, consistent with only parent
      radioligand and not radiometabolites entering the brain. Whole-body scans
      confirmed that the brain had specific (i.e., displaceable) binding but could not
      detect specific binding in peripheral organs. The effective dose for humans
      estimated from the baseline scans in monkeys was 5.0 MUSv/MBq. CONCLUSION: (11)C
      NOP-1A is a useful radioligand for quantifying NOP receptors in the monkey brain,
      and its radiation dose is similar to that of other (11)C-labeled ligands for
      neuroreceptors. (11)C-NOP-1A appears to be a promising candidate for measuring
      NOP receptors in the human brain.

PMID- 21880577
TI  - Phylogenetic analysis based on spectral methods.
AB  - Whole-genome or multiple gene phylogenetic analysis is of interest since single
      gene analysis often results in poorly resolved trees. Here, the use of spectral
      techniques for analyzing multigene data sets is explored. The protein sequences
      are treated as categorical time series, and a measure of similarity between a
      pair of sequences, the spectral covariance, is based on the common periodicity
      between these two sequences. Unlike the other methods, the spectral covariance
      method focuses on the relationship between the sites of genetic sequences. By
      properly scaling the dissimilarity measures derived from different genes between
      a pair of species, we can use the mean of these scaled dissimilarity measures as
      a summary statistic to measure the taxonomic distances across multiple genes. The
      methods are applied to three different data sets, one noncontroversial and two
      with some dispute over the correct placement of the taxa in the tree. Trees are
      constructed using two distance-based methods, BIONJ and FITCH. A variation of
      block bootstrap sampling method is used for inference. The methods are able to
      recover all major clades in the corresponding reference trees with moderate to
      high bootstrap support. Through simulations, we show that the covariance-based
      methods effectively capture phylogenetic signal even when structural information
      is not fully retained. Comparisons of simulation results with the bootstrap
      permutation results indicate that the covariance-based methods are fairly robust
      under perturbations in sequence similarity but more sensitive to perturbations in
      structural similarity.

PMID- 21880578
TI  - The effect of including cystatin C or creatinine in a cardiovascular risk model
      for asymptomatic individuals: the multi-ethnic study of atherosclerosis.
AB  - The authors studied the incremental value of adding serum cystatin C or
      creatinine to the Framingham risk score variables (FRSVs) for the prediction of
      incident cardiovascular disease (CVD) among 6,653 adults without clinical CVD
      utilizing the Multi-Ethnic Study of Atherosclerosis (2000-2008). CVD events
      included coronary heart disease, heart failure, stroke, and peripheral arterial
      disease. Variables were transformed to yield optimal prediction of 6-year CVD
      events in sex-stratified models with FRSVs alone, FRSVs + cystatin C, and FRSVs +
      creatinine. Risk prediction in the 3 models was assessed by using the C
      statistic, and net reclassification improvement was calculated. The mean ages
      were 61.9 and 64.6 years for individuals with and without diabetes, respectively.
      After 6 years of follow-up, 447 (7.2%) CVD events occurred. In the total cohort,
      no significant change in the C statistic was noted with FRSVs + cystatin C and
      FRSVs + creatinine compared with FRSVs alone, and net reclassification
      improvement for CVD risk was extremely small and not significant with the
      addition of cystatin C or creatinine to FRSVs. Similar findings were noted after
      stratifying by baseline presence of diabetes. In conclusion, the addition of
      cystatin C or serum creatinine to FRSVs does not improve CVD risk prediction
      among adults without clinical CVD.

PMID- 21880579
TI  - The transcription factor PAX2 regulates ADAM10 expression in renal cell
      carcinoma.
AB  - ADAM10 is a metalloprotease that plays an important role in the progression and
      metastasis of various cancers. In the present study, we present compelling
      evidence that PAX2 can bind to the promotor of ADAM10 and regulate ADAM10 protein
      expression in renal cancer cells. We further show that ADAM10 is the major
      sheddase for the constitutive cleavage of L1-CAM and c-Met, two important
      proteins involved in the progression of renal cancer. The downregulation of
      ADAM10 led to a more scattered cell phenotype, which was accompanied by the
      induction of Slug and the loss of E-cadherin, which is observed during epithelial
      to-mesenchymal transition (EMT). In addition, the downregulation of ADAM10
      reduced the proliferation but induced the migration of renal cancer cells.
      Notably, the downregulation of PAX2 led to an increased L1-CAM expression, which
      was accompanied by a massive metalloprotease-mediated release of soluble L1-CAM.
      Importantly, soluble L1-CAM induced the proliferation of endothelial cells and
      the migration of renal cancer cells. Finally, we can demonstrate that the
      silencing of PAX2 led to an L1-CAM-dependent activation of the PI3K/Akt pathway,
      one important pathway mediating cancer cell survival. In summary, we identified
      PAX2 as a regulator of L1-CAM and ADAM10, which play crucial roles in the
      progression of various cancers including renal cell carcinoma and the
      downregulation of ADAM10 maybe an earlier step in renal cancer development as it
      seems to be involved in processes of EMT.

PMID- 21880580
TI  - Interaction between functional polymorphic variants in cytokine genes,
      established risk factors and susceptibility to basal cell carcinoma of skin.
AB  - Basal cell carcinoma (BCC) of the skin is the most common neoplasm among the
      Caucasian population of the Western world. Inflammation may result in oxidative
      stress and contribute to promotion and progression of tumors, including BCC. The
      role of cytokines, which are inflammatory modulators, in the biology of tumors
      has been extensively studied and it is well known that they are aberrantly
      produced by cancer cells, macrophages and other phagocytic cells. Genetic
      polymorphisms are known in several cytokine genes, which result in altered
      expression. In the present association study, we investigated the association of
      14 functional polymorphisms in 11 cytokines genes with BCC risk in 529 BCC cases
      and 532 healthy controls. We have also tested the possible interactions between
      the genetic variants and three known risk factors for BCC: skin complexion, sun
      effect and skin response to sun exposure. We did not observe any statistically
      significant association between SNPs and BCC risk. However, we found that, in a
      subgroup of subjects more prone to skin burns, carriers of at least one copy of
      the G allele of rs1800629 (TNF) had an increased risk of BCC [odds ratio (OR) =
      2.40, 95% confidence interval (CI) 1.38-4.16, P = 0.0005]. Moreover, in subjects
      less prone to sunburns, we observed that carriers of the C allele of rs1143627
      (IL1B) showed a decreased risk (OR = 0.53, 95% CI 0.34-0.82, P = 0.0019). In
      conclusion, we found that two polymorphisms in inflammatory genes interacting
      with environmental risk factors could modulate BCC risk.

PMID- 21880581
TI  - Severity of disease and clinical outcomes in patients with hospital-acquired
      pneumonia due to methicillin-resistant Staphylococcus aureus strains not
      influenced by the presence of the Panton-Valentine leukocidin gene.
AB  - BACKGROUND: Patients with community-acquired pneumonia (CAP) infected with
      methicillin-resistant Staphylococcus aureus (MRSA) strains carrying the Panton
      Valentine leukocidin (PVL) gene have severe clinical presentation and poor
      clinical outcomes. Antibiotics that suppress toxin production have been suggested
      for the management of these patients. The objective of this study was to compare
      the severity of disease and clinical outcomes of patients with hospital-acquired
      pneumonia/ventilator-associated pneumonia (HAP/VAP) infected with MRSA carrying
      the PVL gene with those patients infected with MRSA strains that do not carry the
      PVL gene. METHODS: This was a multicenter observational study of patients with
      HAP and VAP. MRSA isolates were subjected to genetic analysis to define the
      presence of the PVL gene, the USA type and the staphylococcal cassette chromosome
      mec type. Severity of disease was evaluated with the Acute Physiology and Chronic
      Health Evaluation II (APACHE II) score. The primary clinical outcome was
      mortality at hospital discharge. RESULTS: A total of 109 cases of MRSA HAP/VAP
      were evaluated. The incidence of PVL(+) MRSA was 27%. APACHE II score at
      diagnosis of HAP/VAP was 21 +/- 8 for PVL(+) MRSA and 20 +/- 6 for PVL(-) MRSA (P
      = .67). Mortality was 10% (3/29) for patients with PVL(+) MRSA versus 10% (8/80)
      for patients with PVL(-) MRSA (P > .99). CONCLUSIONS: In patients with HAP or VAP
      due to MRSA, severity of disease and clinical outcomes are not influenced by the
      presence of the PVL gene. Therapeutic strategies directed to block PVL exotoxin
      may not impact outcomes in these patients.

PMID- 21880582
TI  - Prolonged survival of hepatitis C virus in the anesthetic propofol.

PMID- 21880583
TI  - Predictors of clinical virulence in community-onset methicillin-resistant
      Staphylococcus aureus infections: the importance of USA300 and pneumonia.
AB  - BACKGROUND: Though USA300 community-onset methicillin-resistant Staphylococcus
      aureus (CO-MRSA) has emerged as a major public health concern in the United
      States, its relative virulence is unknown. We sought to evaluate if the USA300
      strain of CO-MRSA causes more severe infections than other MRSA (ie, USA100, 
      500, -800, and others) strains. METHODS: An epidemiologic study was conducted
      from 2000 to 2007 to measure rates of severe infection. A matched case-control
      study was conducted from 2004 to 2006 to assess the relationship of strain type,
      syndrome, and severity of infection. Severe illness was defined as CO-MRSA
      infections with medical intensive care unit (MICU) admission or death within 1
      week of admission. Controls were those with CO-MRSA infection without MICU
      admission. RESULTS: We found an incidence of 75 cases per 100000 people of CO
      MRSA infection in 2000, which increased to a rate of 396 per 100000 in 2007
      (relative risk [RR], 5.3; 95% confidence interval [CI], 4.47-6.27). The incidence
      of severe infections increased from 5 cases per 100000 in 2000 to 17 per 100000
      in 2007 (RR, 3.4; 95% CI; 1.67-6.43). USA300 strains were negatively associated
      with severe clinical courses or death as compared with other MRSA strain types.
      The highest risk of severe infection was found in those with pulmonary embolic
      infiltrates and bacteremia in the setting of USA300 infection (odds ratio, 31.41;
      95% CI, 6.40-154.23). CONCLUSIONS: Our findings suggest that USA300 infections
      are negatively associated with severe clinical courses, suggesting less virulence
      than other MRSA strains, except in the setting of pneumonia with septic pulmonary
      emboli.

PMID- 21880584
TI  - Best alternative to vancomycin for serious methicillin-resistant Staphylococcus
      aureus infections: let's just say it.

PMID- 21880585
TI  - Vancomycin therapeutic guidelines: closer examination of neonatal
      pharmacokinetics.

PMID- 21880586
TI  - Treatment of parainfluenza 3 infection with DAS181 in a patient after allogeneic
      stem cell transplantation.
AB  - Parainfluenza virus (PIV) can cause significant morbidity after allogeneic stem
      cell transplantation (SCT). We report the first use of inhaled DAS181 for PIV in
      an allogeneic SCT recipient. Symptoms, oxygenation, and pulmonary function tests
      improved. Nasopharyngeal samples showed a reduction in viral load. DAS181 should
      be systematically evaluated for severe PIV infection.

PMID- 21880587
TI  - The management of community-acquired pneumonia in infants and children older than
      3 months of age: clinical practice guidelines by the Pediatric Infectious
      Diseases Society and the Infectious Diseases Society of America.
AB  - Evidenced-based guidelines for management of infants and children with community
      acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians
      and investigators representing community pediatrics, public health, and the
      pediatric specialties of critical care, emergency medicine, hospital medicine,
      infectious diseases, pulmonology, and surgery. These guidelines are intended for
      use by primary care and subspecialty providers responsible for the management of
      otherwise healthy infants and children with CAP in both outpatient and inpatient
      settings. Site-of-care management, diagnosis, antimicrobial and adjunctive
      surgical therapy, and prevention are discussed. Areas that warrant future
      investigations are also highlighted.

PMID- 21880588
TI  - Expression and immunotherapeutic targeting of the SSX family of cancer-testis
      antigens in prostate cancer.
AB  - Recent U.S. Food and Drug Administration approval of the first immunotherapy for
      prostate cancer encourages efforts to improve immune targeting of this disease.
      The synovial sarcoma X chromosome breakpoint (SSX) proteins comprise a set of
      cancer-testis antigens that are upregulated in MHC class I-deficient germline
      cells and in various types of advanced cancers with a poor prognosis. Humoral and
      cell-mediated immune responses to the SSX family member SSX2 can arise
      spontaneously in prostate cancer patients. Thus, SSX2 and other proteins of the
      SSX family may offer useful targets for tumor immunotherapy. In this study, we
      evaluated the expression of SSX family members in prostate cancer cell lines and
      tumor biopsies to identify which members might be most appropriate for immune
      targeting. We found that SSX2 was expressed most frequently in prostate cell
      lines, but that SSX1 and SSX5 were also expressed after treatment with the DNA
      demethylating agent 5-aza-2'-deoxycytidine. Immunohistochemical analysis of
      microarrayed tissue biopsies confirmed a differential level of SSX protein
      expression in human prostate cancers. Notably, SSX expression in patient tumor
      samples was restricted to metastatic lesions (5/22; 23%) and no expression was
      detected in primary prostate tumors examined (0/73; P < 0.001). We determined
      that cross-reactive immune responses to a dominant HLA-A2-specific SSX epitope
      (p103-111) could be elicited by immunization of A2/DR1 transgenic mice with SSX
      vaccines. Our findings suggest that multiple SSX family members are expressed in
      metastatic prostate cancers which are amenable to simultaneous targeting.

PMID- 21880589
TI  - Tissue factor-activated coagulation cascade in the tumor microenvironment is
      critical for tumor progression and an effective target for therapy.
AB  - Tissue factor (TF), a rate-limiting enzyme cofactor in activating coagulation, is
      highly expressed in a wide spectrum of human tumor and tumor stromal cells. Using
      TF-deficient cancer cells and a conditional TF-knockout mouse model, we show that
      TF expressed by cancer cells, but not by the host stromal cells, plays a critical
      role in tumor growth. In the tumor microenvironment, serum coagulation factors
      are readily extravasated and therefore lead to continuous TF-mediated activation
      of coagulation proteases. To target this highly specific cascade of serine
      proteases, we used both a TF:VIIa inhibitor and doxorubicin-based prodrugs that
      are selectively activated by TF:FVIIa, FXa, and thrombin. Treatment with the
      TF:FVIIa inhibitor led to growth retardation in breast tumor models. In contrast,
      treatment with the prodrug eliminated primary tumor cells and lung metastases
      without apparent toxicity. Our findings offer preclinical proof of principle that
      targeting the coagulation cascade that is activated in the tumor microenvironment
      can be a highly effective approach for cancer therapy.

PMID- 21880590
TI  - Profiling of the BRCA1 transcriptome through microarray and ChIP-chip analysis.
AB  - A role for BRCA1 in the direct and indirect regulation of transcription is well
      established. However, a comprehensive view of the degree to which BRCA1 impacts
      transcriptional regulation on a genome-wide level has not been defined. We
      performed genome-wide expression profiling and ChIP-chip analysis, comparison of
      which revealed that although BRCA1 depletion results in transcriptional changes
      in 1294 genes, only 44 of these are promoter bound by BRCA1. However, 27% of
      these transcripts were linked to transcriptional regulation possibly explaining
      the large number of indirect transcriptional changes observed by microarray
      analysis. We show that no specific consensus sequence exists for BRCA1 DNA
      binding but rather demonstrate the presence of a number of known and novel
      transcription factor (TF)- binding sites commonly found on BRCA1 bound promoters.
      Co-immunoprecipitations confirmed that BRCA1 interacts with a number of these TFs
      including AP2-alpha, PAX2 and ZF5. Finally, we show that BRCA1 is bound to a
      subset of promoters of genes that are not altered by BRCA1 loss, but are
      transcriptionally regulated in a BRCA1-dependent manner upon DNA damage. These
      data suggest a model, whereby BRCA1 is present on defined promoters as part of an
      inactive complex poised to respond to various genotoxic stimuli.

PMID- 21880591
TI  - Nuclear colocalization of transcription factor target genes strengthens
      coregulation in yeast.
AB  - Eukaryotic chromosomes are not randomly distributed in the interphase nucleus,
      but instead occupy distinct territories. Nonetheless, the genome-wide
      relationships of gene regulation to gene nuclear location remain poorly
      understood in yeast. In the three-dimensional view of gene regulation, we found
      that a considerable number of transcription factors (TFs) regulate genes that are
      colocalized in the nucleus. Colocalized TF target genes are more strongly
      coregulated compared with the other TF target genes. Target genes of chromatin
      regulators are also colocalized. These results demonstrate that colocalization of
      coregulated genes is a common process, and three-dimensional gene positioning is
      an important part of gene regulation. Our findings will have implications in
      understanding nuclear architecture and function.

PMID- 21880592
TI  - Direct cloning of double-stranded RNAs from RNase protection analysis reveals
      processing patterns of C/D box snoRNAs and provides evidence for widespread
      antisense transcript expression.
AB  - We describe a new method that allows cloning of double-stranded RNAs (dsRNAs)
      that are generated in RNase protection experiments. We demonstrate that the mouse
      C/D box snoRNA MBII-85 (SNORD116) is processed into at least five shorter RNAs
      using processing sites near known functional elements of C/D box snoRNAs.
      Surprisingly, the majority of cloned RNAs from RNase protection experiments were
      derived from endogenous cellular RNA, indicating widespread antisense expression.
      The cloned dsRNAs could be mapped to genome areas that show RNA expression on
      both DNA strands and partially overlapped with experimentally determined
      argonaute-binding sites. The data suggest a conserved processing pattern for some
      C/D box snoRNAs and abundant expression of longer, non-coding RNAs in the cell
      that can potentially form dsRNAs.

PMID- 21880593
TI  - Ku counteracts mobilization of PARP1 and MRN in chromatin damaged with DNA double
      strand breaks.
AB  - In mammalian cells, the main pathway for DNA double-strand breaks (DSBs) repair
      is classical non-homologous end joining (C-NHEJ). An alternative or back-up NHEJ
      (B-NHEJ) pathway has emerged which operates preferentially under C-NHEJ defective
      conditions. Although B-NHEJ appears particularly relevant to genomic instability
      associated with cancer, its components and regulation are still largely unknown.
      To get insights into this pathway, we have knocked-down Ku, the main contributor
      to C-NHEJ. Thus, models of human cell lines have been engineered in which the
      expression of Ku70/80 heterodimer can be significantly lowered by the conditional
      induction of a shRNA against Ku70. On Ku reduction in cells, resulting NHEJ
      competent protein extracts showed a shift from C- to B-NHEJ that could be
      reversed by addition of purified Ku protein. Using a cellular fractionation
      protocol after treatment with a strong DSBs inducer followed by western blotting
      or immunostaining, we established that, among C-NHEJ factors, Ku is the main
      counteracting factor against mobilization of PARP1 and the MRN complex to damaged
      chromatin. In addition, Ku limits PAR synthesis and single-stranded DNA
      production in response to DSBs. These data support the involvement of PARP1 and
      the MRN proteins in the B-NHEJ route for the repair of DNA DSBs.

PMID- 21880594
TI  - Guiding strand passage: DNA-induced movement of the gyrase C-terminal domains
      defines an early step in the supercoiling cycle.
AB  - DNA gyrase catalyzes ATP-dependent negative supercoiling of DNA in a strand
      passage mechanism. A double-stranded segment of DNA, the T-segment, is passed
      through the gap in a transiently cleaved G-segment by coordinated closing and
      opening of three protein interfaces in gyrase. T-segment capture is thought to be
      guided by the C-terminal domains of the GyrA subunit of gyrase that wrap DNA
      around their perimeter and cause a DNA-crossing with a positive handedness. We
      show here that the C-terminal domains are in a downward-facing orientation in the
      absence of DNA, but swing up and rotate away from the gyrase body when DNA binds.
      The upward movement of the C-terminal domains is an early event in the catalytic
      cycle of gyrase that is triggered by binding of a G-segment, and first contacts
      of the DNA with the C-terminal domains, and contributes to T-segment capture and
      subsequent strand passage.

PMID- 21880595
TI  - A novel three-unit tRNA splicing endonuclease found in ultrasmall Archaea
      possesses broad substrate specificity.
AB  - tRNA splicing endonucleases, essential enzymes found in Archaea and Eukaryotes,
      are involved in the processing of pre-tRNA molecules. In Archaea, three types of
      splicing endonuclease [homotetrameric: alpha(4), homodimeric: alpha(2), and
      heterotetrameric: (alphabeta)(2)] have been identified, each representing
      different substrate specificity during the tRNA intron cleavage. Here, we
      discovered a fourth type of archaeal tRNA splicing endonuclease (epsilon(2)) in
      the genome of the acidophilic archaeon Candidatus Micrarchaeum acidiphilum,
      referred to as ARMAN-2 and its closely related species, ARMAN-1. The enzyme
      consists of two duplicated catalytic units and one structural unit encoded on a
      single gene, representing a novel three-unit architecture. Homodimeric formation
      was confirmed by cross-linking assay, and site-directed mutagenesis determined
      that the conserved L10-pocket interaction between catalytic and structural unit
      is necessary for the assembly. A tRNA splicing assay reveal that epsilon(2)
      endonuclease cleaves both canonical and non-canonical bulge-helix-bulge motifs,
      similar to that of (alphabeta)(2) endonuclease. Unlike other ARMAN and
      Euryarchaeota, tRNAs found in ARMAN-2 are highly disrupted by introns at various
      positions, which again resemble the properties of archaeal species with
      (alphabeta)(2) endonuclease. Thus, the discovery of epsilon(2) endonuclease in an
      archaeon deeply branched within Euryarchaeota represents a new example of the
      coevolution of tRNA and their processing enzymes.

PMID- 21880596
TI  - Far upstream element binding protein 1 binds the internal ribosomal entry site of
      enterovirus 71 and enhances viral translation and viral growth.
AB  - Enterovirus 71 (EV71) is associated with severe neurological disorders in
      children, and has been implicated as the infectious agent in several large-scale
      outbreaks with mortalities. Upon infection, the viral RNA is translated in a cap
      independent manner to yield a large polyprotein precursor. This mechanism relies
      on the presence of an internal ribosome entry site (IRES) element within the 5'
      untranslated region. Virus-host interactions in EV71-infected cells are crucial
      in assisting this process. We identified a novel positive IRES trans-acting
      factor, far upstream element binding protein 1 (FBP1). Using binding assays, we
      mapped the RNA determinants within the EV71 IRES responsible for FBP1 binding and
      mapped the protein domains involved in this interaction. We also demonstrated
      that during EV71 infection, the nuclear protein FBP1 is enriched in cytoplasm
      where viral replication occurs. Moreover, we showed that FBP1 acts as a positive
      regulator of EV71 replication by competing with negative ITAF for EV71 IRES
      binding. These new findings may provide a route to new anti-viral therapy.

PMID- 21880597
TI  - Treatment of breast cancer cells with DNA demethylating agents leads to a release
      of Pol II stalling at genes with DNA-hypermethylated regions upstream of TSS.
AB  - Inactivation of tumor suppressor genes plays an important role in tumorigenesis,
      and epigenetic modifications such as DNA methylation are frequently associated
      with transcriptional repression. Here, we show that gene silencing at selected
      genes with signs of DNA hypermethylation in breast cancer cells involves Pol II
      stalling. We studied several repressed genes with DNA hypermethylation within a
      region 1-kb upstream of the transcriptional start site that were upregulated
      after treatment with DNA demethylating agents, such as Azacytidine and several
      natural products. All those selected genes had stalled Pol II at their
      transcriptional start site and showed enhanced ser2 phosphorylated Pol II and
      elevated transcripts after drug treatment indicating successful elongation. In
      addition, a decrease of the epigenetic regulator LSH in a breast cancer cell line
      by siRNA treatment reduced DNA methylation and overcame Pol II stalling, whereas
      overexpression of LSH in a normal breast epithelial cell line increased DNA
      methylation and resulted in repression. Decrease of LSH was associated with
      reduced DNMT3b binding to promoter sequences, and depletion of DNMT3b by siRNA
      could release Pol II suggesting that DNMT3b is functionally involved. The release
      of paused Pol II was accompanied by a dynamic switch from repressive to active
      chromatin marks. Thus release of Pol II stalling can act as a mechanism for gene
      reactivation at specific target genes after DNA demethylating treatment in cancer
      cells.

PMID- 21880599
TI  - Duplex-specific nuclease efficiently removes rRNA for prokaryotic RNA-seq.
AB  - Next-generation sequencing has great potential for application in bacterial
      transcriptomics. However, unlike eukaryotes, bacteria have no clear mechanism to
      select mRNAs over rRNAs; therefore, rRNA removal is a critical step in sequencing
      based transcriptomics. Duplex-specific nuclease (DSN) is an enzyme that, at high
      temperatures, degrades duplex DNA in preference to single-stranded DNA. DSN
      treatment has been successfully used to normalize the relative transcript
      abundance in mRNA-enriched cDNA libraries from eukaryotic organisms. In this
      study, we demonstrate the utility of this method to remove rRNA from prokaryotic
      total RNA. We evaluated the efficacy of DSN to remove rRNA by comparing it with
      the conventional subtractive hybridization (Hyb) method. Illumina deep sequencing
      was performed to obtain transcriptomes from Escherichia coli grown under four
      growth conditions. The results clearly showed that our DSN treatment was more
      efficient at removing rRNA than the Hyb method was, while preserving the original
      relative abundance of mRNA species in bacterial cells. Therefore, we propose
      that, for bacterial mRNA-seq experiments, DSN treatment should be preferred to
      Hyb-based methods.

PMID- 21880598
TI  - Transcription factories in the context of the nuclear and genome organization.
AB  - In the eukaryotic nucleus, genes are transcribed in transcription factories. In
      the present review, we re-evaluate the models of transcription factories in the
      light of recent and older data. Based on this analysis, we propose that
      transcription factories result from the aggregation of RNA polymerase II
      containing pre-initiation complexes assembled next to each other in the nuclear
      space. Such an aggregation can be triggered by the phosphorylation of the C
      terminal domain of RNA polymerase II molecules and their interaction with various
      transcription factors. Individual transcription factories would thus incorporate
      tissue-specific, co-regulated as well as housekeeping genes based only on their
      initial proximity to each other in the nuclear space. Targeting genes to be
      transcribed to protein-dense factories that contain all factors necessary for
      transcription initiation and elongation through chromatin templates clearly
      favors a more economical utilization and better recycling of the transcription
      machinery.

PMID- 21880602
TI  - The First AACR special conference on stem cells, development, and cancer: some of
      these cells are not like the others.
AB  - The American Association for Cancer Research (AACR) held an exciting conference
      on Stem Cells, Development, and Cancer in Vancouver, British Columbia, Canada
      (March 3-6, 2011). The meeting was cochaired by Geoffrey Wahl, Connie Eaves, and
      Hans Clevers and was attended by 250 international researchers, 40% of whom were
      young investigators. Three key themes emerged: (i) heterogeneity in stem cells
      and cancer, (ii) solid tissue cancer stem cells, and (iii) lessons from
      development. The interdisciplinary foundation of this meeting was central to its
      success and appeal, underscoring the value of juxtaposing and interrelating work
      from the three topics addressed.

PMID- 21880600
TI  - Activation-induced disruption of nucleosome position clusters on the coding
      regions of Gcn4-dependent genes extends into neighbouring genes.
AB  - We have used paired-end sequencing of yeast nucleosomal DNA to obtain accurate
      genomic maps of nucleosome positions and occupancies in control cells and cells
      treated with 3-aminotriazole (3AT), an inducer of the transcriptional activator
      Gcn4. In control cells, 3AT-inducible genes exhibit a series of distinct
      nucleosome occupancy peaks. However, the underlying position data reveal that
      each nucleosome peak actually consists of a cluster of mutually exclusive
      overlapping positions, usually including a dominant position. Thus, each
      nucleosome occupies one of several possible positions and consequently, different
      cells have distinct local chromatin structures. Induction results in a major
      disruption of nucleosome positioning, sometimes with altered spacing and a
      dramatic loss of occupancy over the entire gene, often extending into a
      neighbouring gene. Nucleosome-depleted regions are generally unaffected. Genes
      repressed by 3AT show the same changes, but in reverse. We propose that yeast
      genes exist in one of several alternative nucleosomal arrays, which are disrupted
      by activation. We conclude that activation results in gene-wide chromatin
      remodelling and that this remodelling can even extend into the chromatin of
      flanking genes.

PMID- 21880603
TI  - BMP2 and VEGF promote angiogenesis but retard terminal differentiation of
      osteoblasts in bone regeneration by up-regulating Id1.
AB  - Inadequate vascularization limits the repair of bone defects. In order to improve
      angiogenesis and accelerate osteogenesis, the synergism of co-cultured cells with
      genetic modification in bone regeneration was investigated in this study.
      Endothelial progenitor cells (EPCs) and bone marrow stem cells (BMSCs) were
      transfected with the genes of vascular endothelial growth factor (VEGF) and bone
      morphogenetic protein 2 (BMP2) by adenovirus, respectively. The co-cultured
      cells, designated as four groups including BMSC + EPC, Ad-BMP2-BMSC + EPC, BMSC +
      Ad-VEGF-EPC, and Ad-BMP2-BMSC + Ad-VEGF-EPC groups, were seeded on an alginate
      gel and then implanted into rat intramuscularly to evaluate the effects on
      angiogenesis and osteogenesis. Both VEGF and BMP2 could induce the overexpression
      of inhibitor of DNA-binding 1(Id1) gene which significantly promoted tube
      formation in vitro and increase the amount of blood vessels in the Ad-BMP2-BMSC +
      Ad-VEGF-EPC group after implantation. Nevertheless, overexpression of Id1
      retarded the terminal differentiation of osteoblasts and the bone formation.
      Later, osteogenic gene expression at transcriptional level, calcium nodules, and
      alkaline phosphatase (ALP) activity showed a gradual decrease and the amount of
      newly formed osteogenesis area exhibited a small increase in the Ad-BMP2-BMSC +
      Ad-VEGF-EPC group. This finding suggests that a balanced regulation of Id1
      expression in VEGF-EPCs and BMP2-BMSCs may be critical to cell-based and gene
      based approaches for bone regeneration.

PMID- 21880604
TI  - Differential mitochondrial calcium responses in different cell types detected
      with a mitochondrial calcium fluorescent indicator, mito-GCaMP2.
AB  - Mitochondrial calcium plays a crucial role in mitochondrial metabolism, cell
      calcium handling, and cell death. However, some mechanisms concerning
      mitochondrial calcium regulation are still unknown, especially how mitochondrial
      calcium couples with cytosolic calcium. In this work, we constructed a novel
      mitochondrial calcium fluorescent indicator (mito-GCaMP2) by genetic
      manipulation. Mito-GCaMP2 was imported into mitochondria with high efficiency and
      the fluorescent signals co-localized with that of tetramethyl rhodamine methyl
      ester, a mitochondrial membrane potential indicator. The mitochondrial inhibitors
      specifically decreased the signals of mito-GCaMP2. The apparent K(d) of mito
      GCaMP2 was 195.0 nmol/L at pH 8.0 in adult rat cardiomyocytes. Furthermore, we
      observed that mito-GCaMP2 preferred the alkaline pH surrounding of mitochondria.
      In HeLa cells, we found that mitochondrial calcium ([Ca(2+)](mito)) responded to
      the changes of cytosolic calcium ([Ca(2+)](cyto)) induced by histamine or
      thapasigargin. Moreover, external Ca(2+) (100 MUmol/L) directly induced an
      increase of [Ca(2+)](mito) in permeabilized HeLa cells. However, in rat
      cardiomyocytes [Ca(2+)](mito) did not respond to cytosolic calcium transients
      stimulated by electric pacing or caffeine. In permeabilized cardiomyocytes, 600
      nmol/L free Ca(2+) repeatedly increased the fluorescent signals of mito-GCaMP2,
      which excluded the possibility that mito-GCaMP2 lost its function in
      cardiomyocytes mitochondria. These results showed that the response of
      mitochondrial calcium is diverse in different cell lineages and suggested that
      mitochondria in cardiomyocytes may have a special defense mechanism to control
      calcium flux.

PMID- 21880605
TI  - Congenital left circumflex artery to left atrial appendage fistula: searching for
      a 'colorful fountain'.

PMID- 21880606
TI  - Prolonged left ventricular twist in cardiomyopathies: a potential link between
      systolic and diastolic dysfunction.
AB  - AIMS: Left ventricular (LV) twist and untwist play a major role in LV mechanics.
      We sought to acquire new pathophysiological insights in cardiomyopathies (CM)
      studying LV twist dynamics by speckle tracking imaging (STI). METHODS AND
      RESULTS: Standard echo-Doppler and STI study were performed in 67 CM patients
      divided in four age- and sex-matched subgroups: 18 with apical hypertrophic
      cardiomyopathy (Group A); 20 with asymmetrical hypertrophic cardiomyopathy (Group
      B); 15 with dilated cardiomyopathy (Group C); 14 with LV non-compaction (Group
      D). As controls, 34 age- and sex-matched normal subjects were studied. Compared
      with control group, all CM Groups showed significantly lower longitudinal,
      circumferential, and radial myocardial deformations (P < 0.05). LV twist was
      correlated with ejection fraction (EF; r = 0.62; P < 0.0001). Furthermore, all CM
      patients had a significantly lower twist rate (P < 0.05) and delayed onset of
      untwist (P < 0.01). Of interest a significant correlation was found between
      isovolumic relaxation time and untwist onset (r= 0.485, P < 0.0001). In addition,
      a significant correlation was found between longitudinal deformations and the
      onset of untwist (strain: r = 0.46, P = 0.0001; strain rate: r = 0.33, P =
      0.0056) and between longitudinal strain rate and twisting rate (r= -0.38; P =
      0.0015). CONCLUSION: (i) All CM patients show an impairment of longitudinal,
      circumferential, and radial myocardial deformations; (ii) LV peak twist is
      impaired only in CM with reduced EF but preserved in those with normal or
      increased EF; (iii) LV twist is prolonged and untwisting onset is delayed in all
      CM, suggesting that a mechanical adaptation to subclinical systolic abnormalities
      might induce, by a prolonged LV twist, the early onset of diastolic dysfunction.

PMID- 21880607
TI  - Resting coronary flow velocity in the functional evaluation of coronary artery
      stenosis: study on sequential use of computed tomography angiography and
      transthoracic Doppler echocardiography.
AB  - AIMS: Accelerated flow at the site of flow-limiting stenosis can be detected by
      transthoracic Doppler echocardiography (TTDE). We studied feasibility and
      accuracy of sequential coronary computed tomography angiography (CTA) and TTDE in
      detection of haemodynamically significant coronary artery disease (CAD). METHODS
      AND RESULTS: We prospectively enrolled 107 patients with intermediate (30-70%)
      pre-test likelihood of CAD. All patients underwent CTA using a 64-slice scanner.
      Using TTDE, the ratio of maximal diastolic flow velocity to pre-stenotic flow
      velocity (M/P ratio) was measured in the coronary segments with stenosis in CTA.
      In all patients, the results were compared with invasive coronary angiography,
      including measurement of fractional flow reserve when appropriate. All analyses
      were done blinded. TTDE was feasible in 276 of 285 evaluated coronary segments.
      Significant coronary stenoses were associated with a higher M/P ratio than non
      significant stenoses (3.59 +/- 1.82 vs. 1.28 +/- 0.60, P < 0.001). The optimal
      M/P ratio for detection of significant stenosis was 2.2 (area under receiver
      operating characteristic curve 0.92, P < 0.001). Compared with the strategy of
      CTA alone, sequential CTA and focused TTDE had a better positive predictive value
      (PPV; 61 vs. 78%) and diagnostic accuracy (93 vs. 96%, P = 0.006) without
      impairment of the negative predictive value (97 vs. 97%). CONCLUSION: Sequential
      use of CTA and TTDE is feasible for combined anatomic and functional evaluation
      of coronary stenoses. Compared with coronary CTA alone, addition of TTDE improved
      PPV for detection of significant CAD.

PMID- 21880608
TI  - Determinants of echocardiographic left atrial volume: implications for normalcy.
AB  - AIMS: The relative role of multiple determinants of left atrial volume index
      (LAVi) in athletes and non-athletes is not fully defined. Thus, we decided to
      prospectively assess the determinants of LAVi in healthy individuals and
      competitive athletes over a wide age range. METHODS AND RESULTS: Four hundred and
      eighteen healthy individuals (mean age 41.7 +/- 15.6 years, range 16-84, 65%
      males, 38% competitive athletes) underwent Doppler echocardiography including
      assessment of LAVi by the biplane area-length method and of left ventricular (LV)
      diastolic function including the ratio of early diastolic peak LV inflow velocity
      to peak myocardial early diastolic velocity (E/e'). Mean LAVi was 32.2 +/- 9.0
      mL/m(2) in the pooled population. LAVi was larger in athletes than in non
      athletes (38.9 +/- 9.6 mL/m(2) vs. 28.4 +/- 5.8 mL/m(2), P < 0.0001). In the
      pooled population a stepwise multiple linear regression analysis identified LV
      end-diastolic volume index (LVEDVi) (beta = 0.378, P < 0.0001), LV mass index
      (LVMi) (beta = 0.260, P < 0.0001), competitive sport activity (beta = 0.258, P <
      0.0001), and age (beta = 0.222, P < 0.0001) as independent determinants of LAVi
      (model R(2) = 0.54, P < 0.0001). By separate analyses, although LVEDVi, age, and
      LVMi were predictors of LAVi in both groups, body mass index and the E/e' ratio
      were additional predictors of LAVi only in non-athletes. CONCLUSIONS: In healthy
      individuals LV size, competitive sport, age, and LV mass are independent
      determinants of LAVi. Body mass index and the E/e' ratio affect LAVi only in non
      athletes. These findings may have practical implications when assessing normalcy
      of LA size in the clinical setting.

PMID- 21880609
TI  - Assessment of right ventricular functions during cancer chemotherapy.
AB  - AIMS: Although systolic and diastolic left ventricular functions after cancer
      chemotherapy are well studied, there are a few investigations about the right
      ventricular functions. We aimed to investigate the early effects of chemotherapy
      on right heart, if any, in addition to the association between N-terminal pro
      brain natriuretic peptide (NT-proBNP) and right heart echocardiographic indices.
      METHODS AND RESULTS: Thirty-seven consecutive patients with newly diagnosed
      breast cancer who were planned to receive either AC protocol [cyclophosphamide
      (600 mg/m(2)) + adriamycin (60 mg/m(2))] or CAF protocol [cyclophosphamide (600
      mg/m(2)) + adriamycin (60 mg/m(2)) + 5-fluorouracil (600 mg/m(2))] for six cures
      were enrolled between February 2009 and June 2010. Echocardiography was performed
      before the onset of the chemotheurapeutic regimen (T1), on the day after the
      completion of the first cure (T2), and after the completion of two cures of the
      regimen (T3). Serum NT-proBNP levels were also measured at T1, T2, and T3. The
      mean right ventricular fractional area change (RVFAC) was 63.7 +/- 3.63, 63.3 +/-
      3.67, and 61.2 +/- 4.41% at T1, T2, and T3, respectively (pT1-T3 and pT2-T3
      <0.05). Tricuspid annular plane systolic excursion (TAPSE) has decreased in time
      (1.82 +/- 0.2, 1.78 +/- 0.19, and 1.62 +/- 0.24 cm; pT1-T2, pT1-T3, and pT2-T3
      were 0.002, <0.001, and <0.001, respectively). Tricuspid annular mean E'/A'
      ratios were 1.42 +/- 0.16, 1.36 +/- 0.18, and 1.11 +/- 0.32 (pT1-T2 = 0.013, pT1
      T3 < 0.001, and pT2-T3 < 0.001). Mean tricuspid annular systolic velocities were
      11.35 +/- 1.85, 11.0 +/- 1.82, and 10.45 +/- 1.75 cm/s for T1, T2, and T3; and
      the differences between T1 and T2, T1 and T3, and T2 and T3 were all significant
      (P = 0.005, <0.001, and 0.001). Median serum NT-proBNP levels were 82 (60-247),
      116 (60-426), and 170 (60-600) pg/mL at T1, T2, and T3. The amount of change in
      RVFAC and TAPSE between T1 and T3 were found to be correlated with the amount of
      change in NT-proBNP measurements between T1 and T3 (R: -0.7, P < 0.001; R: -0.62,
      P < 0.001). CONCLUSION: There is a subclinical decrease in right ventricular
      systolic and diastolic echocardiographic indices, although mostly, in the normal
      range, in a relatively short time interval after onset of chemotherapy.

PMID- 21880610
TI  - Quadricuspid aortic valve: a case study.

PMID- 21880611
TI  - The myocardial architecture of cor triloculare biatrium resembling reptiles.

PMID- 21880612
TI  - Contrast enhancement in the phase plate transmission electron microscopy using an
      objective lens with a long focal length.
AB  - A new optical condition using an objective lens (OL) of a long focal length
      (objective mini lens: OM) was tested to enhance image contrast in phase plate
      transmission electron microscopy (P-TEM). A phase plate was set on the selected
      area aperture plane where diffraction patterns were formed under the optical
      condition using the OM. A phase shift by the phase plate was added to the
      electron waves to visualize phase objects. The application of the OM to the P-TEM
      should provide higher phase contrast than that obtained by the OL for the phase
      objects. One of the reasons for the contrast enhancement is that high-angle
      scattering electron waves which would give the background intensity were not used
      for image formation due to the large spherical aberration. Another reason is that
      the cut-on frequency above which the phase shift was added by the phase plate
      could be smaller using the OL with a long focal length. Experimental results and
      model calculations showed the contrast enhancement of the biological specimens
      using the OM.

PMID- 21880613
TI  - 'About time!' Insights from Research with Pride: a community-student
      collaboration.
AB  - Research with Pride (RwP) was a community-student collaborative initiative to
      promote and build capacity for community-based research exploring health and
      wellness in lesbian, bisexual, trans and queer (LGBTQ) communities. The event
      took place at University of Toronto's Dalla Lana School of Public Health (DLSPH)
      in September 2009, and engaged over 100 students, community members and academic
      researchers in a full day of discussion, learning and networking. RwP was
      initiated by a group of graduate students in Health Promotion who identified a
      gap in resources addressing LGBTQ health, facilitating their further learning and
      work in this area. By engaging in a partnership with a community service
      organization serving LGBTQ communities in downtown Toronto, RwP emerges as a key
      example of the role of community-student partnerships in the pursuit of LGBTQ
      health promotion. This paper will describe the nature of this partnership,
      outline its strengths and challenges and emphasize the integral role of community
      student partnerships in health promotion initiatives.

PMID- 21880614
TI  - Biologically inspired crack delocalization in a high strain-rate environment.
AB  - Biological materials possess unique and desirable energy-absorbing mechanisms and
      structural characteristics worthy of consideration by engineers. For example,
      high levels of energy dissipation at low strain rates via triggering of crack
      delocalization combined with interfacial hardening by platelet interlocking are
      observed in brittle materials such as nacre, the iridescent material in
      seashells. Such behaviours find no analogy in current engineering materials. The
      potential to mimic such toughening mechanisms on different length scales now
      exists, but the question concerning their suitability under dynamic loading
      conditions and whether these mechanisms retain their energy-absorbing potential
      is unclear. This paper investigates the kinematic behaviour of an 'engineered'
      nacre-like structure within a high strain-rate environment. A finite-element (FE)
      model was developed which incorporates the pertinent biological design features.
      A parametric study was carried out focusing on (i) the use of an overlapping
      discontinuous tile arrangement for crack delocalization and (ii) application of
      tile waviness (interfacial hardening) for improved post-damage behaviour. With
      respect to the material properties, the model allows the permutation and
      combination of a variety of different material datasets. The advantage of such a
      discontinuous material shows notable improvements in sustaining high strain-rate
      deformation relative to an equivalent continuous morphology. In the case of the
      continuous material, the shockwaves propagating through the material lead to
      localized failure while complex shockwave patterns are observed in the
      discontinuous flat tile arrangement, arising from platelet interlocking. The
      influence of the matrix properties on impact performance is investigated by
      varying the dominant material parameters. The results indicate a deceleration of
      the impactor velocity, thus delaying back face nodal displacement. A final series
      of FE models considered the identification of an optimized configuration as a
      function of tile waviness and matrix properties. In the combined model, the
      optimized configuration was capable of stopping the ballistic threat, thus
      indicating the potential for bioinspired toughened synthetic systems to defeat
      high strain-rate threats.

PMID- 21880615
TI  - Kinematic measures for assessing gait stability in elderly individuals: a
      systematic review.
AB  - Falls not only present a considerable health threat, but the resulting treatment
      and loss of working days also place a heavy economic burden on society. Gait
      instability is a major fall risk factor, particularly in geriatric patients, and
      walking is one of the most frequent dynamic activities of daily living. To allow
      preventive strategies to become effective, it is therefore imperative to identify
      individuals with an unstable gait. Assessment of dynamic stability and gait
      variability via biomechanical measures of foot kinematics provides a viable
      option for quantitative evaluation of gait stability, but the ability of these
      methods to predict falls has generally not been assessed. Although various
      methods for assessing gait stability exist, their sensitivity and applicability
      in a clinical setting, as well as their cost-effectiveness, need verification.
      The objective of this systematic review was therefore to evaluate the sensitivity
      of biomechanical measures that quantify gait stability among elderly individuals
      and to evaluate the cost of measurement instrumentation required for application
      in a clinical setting. To assess gait stability, a comparative effect size
      (Cohen's d) analysis of variability and dynamic stability of foot trajectories
      during level walking was performed on 29 of an initial yield of 9889 articles
      from four electronic databases. The results of this survey demonstrate that
      linear variability of temporal measures of swing and stance was most capable of
      distinguishing between fallers and non-fallers, whereas step width and stride
      velocity prove more capable of discriminating between old versus young (OY)
      adults. In addition, while orbital stability measures (Floquet multipliers)
      applied to gait have been shown to distinguish between both elderly fallers and
      non-fallers as well as between young and old adults, local stability measures
      (lambdas) have been able to distinguish between young and old adults. Both linear
      and nonlinear measures of foot time series during gait seem to hold predictive
      ability in distinguishing healthy from fall-prone elderly adults. In conclusion,
      biomechanical measurements offer promise for identifying individuals at risk of
      falling and can be obtained with relatively low-cost tools. Incorporation of the
      most promising measures in combined retrospective and prospective studies for
      understanding fall risk and designing preventive strategies is warranted.

PMID- 21880616
TI  - A systems approach to model the relationship between aflatoxin gene cluster
      expression, environmental factors, growth and toxin production by Aspergillus
      flavus.
AB  - A microarray analysis was used to examine the effect of combinations of water
      activity (a(w), 0.995-0.90) and temperature (20-42 degrees C) on the activation
      of aflatoxin biosynthetic genes (30 genes) in Aspergillus flavus grown on a
      conducive YES (20 g yeast extract, 150 g sucrose, 1 g MgSO(4).7H(2)O) medium. The
      relative expression of 10 key genes (aflF, aflD, aflE, aflM, aflO, aflP, aflQ,
      aflX, aflR and aflS) in the biosynthetic pathway was examined in relation to
      different environmental factors and phenotypic aflatoxin B(1) (AFB(1))
      production. These data, plus data on relative growth rates and AFB(1) production
      under different a(w) * temperature conditions were used to develop a mixed-growth
      associated product formation model. The gene expression data were normalized and
      then used as a linear combination of the data for all 10 genes and combined with
      the physical model. This was used to relate gene expression to a(w) and
      temperature conditions to predict AFB(1) production. The relationship between the
      observed AFB(1) production provided a good linear regression fit to the predicted
      production based in the model. The model was then validated by examining datasets
      outside the model fitting conditions used (37 degrees C, 40 degrees C and
      different a(w) levels). The relationship between structural genes (aflD, aflM) in
      the biosynthetic pathway and the regulatory genes (aflS, aflJ) was examined in
      relation to a(w) and temperature by developing ternary diagrams of relative
      expression. These findings are important in developing a more integrated systems
      approach by combining gene expression, ecophysiological influences and growth
      data to predict mycotoxin production. This could help in developing a more
      targeted approach to develop prevention strategies to control such carcinogenic
      natural metabolites that are prevalent in many staple food products. The model
      could also be used to predict the impact of climate change on toxin production.

PMID- 21880617
TI  - Stochastic properties of the plant circadian clock.
AB  - Circadian clocks are gene regulatory networks whose role is to help the organisms
      to cope with variations in environmental conditions such as the day/night cycle.
      In this work, we explored the effects of molecular noise in single cells on the
      behaviour of the circadian clock in the plant model species Arabidopsis thaliana.
      The computational modelling language Bio-PEPA enabled us to give a stochastic
      interpretation of an existing deterministic model of the clock, and to easily
      compare the results obtained via stochastic simulation and via numerical solution
      of the deterministic model. First, the introduction of stochasticity in the model
      allowed us to estimate the unknown size of the system. Moreover, stochasticity
      improved the description of the available experimental data in several light
      conditions: noise-induced fluctuations yield a faster entrainment of the plant
      clock under certain photoperiods and are able to explain the experimentally
      observed dampening of the oscillations in plants under constant light conditions.
      The model predicts that the desynchronization between noisy oscillations in
      single cells contributes to the observed damped oscillations at the level of the
      cell population. Analysis of the phase, period and amplitude distributions under
      various light conditions demonstrated robust entrainment of the plant clock to
      light/dark cycles which closely matched the available experimental data.

PMID- 21880618
TI  - There is always a trade-off between speed and force in a lever system: comment on
      McHenry (2010).

PMID- 21880620
TI  - Shifting the life-history paradigm: discovery of novel habitat use by hawksbill
      turtles.
AB  - Adult hawksbill turtles (Eretmochelys imbricata) are typically described as open
      coast, coral reef and hard substrate dwellers. Here, we report new satellite
      tracking data on female hawksbills from several countries in the eastern Pacific
      that revealed previously undocumented behaviour for adults of the species. In
      contrast to patterns of habitat use exhibited by their Caribbean and Indo-Pacific
      counterparts, eastern Pacific hawksbills generally occupied inshore estuaries,
      wherein they had strong associations with mangrove saltwater forests. The use of
      inshore habitats and affinities with mangrove saltwater forests presents a
      previously unknown life-history paradigm for adult hawksbill turtles and suggests
      a potentially unique evolutionary trajectory for the species. Our findings
      highlight the variability in life-history strategies that marine turtles and
      other wide-ranging marine wildlife may exhibit among ocean regions, and the
      importance of understanding such disparities from an ecological and management
      perspective.

PMID- 21880621
TI  - Masculinized female yellow-bellied marmots initiate more social interactions.
AB  - The presence of male siblings in utero influences female morphology and life
      history traits because testosterone transferred among foetuses may masculinize
      females. Similarly, litter sex composition might alter the display of sexually
      dimorphic behaviour, such as play and allogrooming, since they are modulated by
      androgens. We explored whether masculinization alters the frequency of play and
      sociopositive behaviour in female yellow-bellied marmots (Marmota flaviventris).
      We found that masculinized juvenile females were more likely to initiate play and
      allogrooming, but yearling females exhibited higher levels of oestrogen-modulated
      sociopositive behaviours. Additionally, the more they interacted, the greater
      number of different partners they interacted with. Our results suggest that
      masculinization increases the rate of age-dependent social behaviour. This
      probably works by increasing exploration that predisposes individuals to higher
      encounter rates. Further support comes from previous findings showing that
      masculinized females were more likely to disperse. Our study stresses the
      importance of considering litter sex composition as a fitness modulator.

PMID- 21880622
TI  - Increased responsiveness in feeding behaviour of Caenorhabditis elegans after
      experimental coevolution with its microparasite Bacillus thuringiensis.
AB  - Immune responses, either constitutive or induced, are costly. An alternative
      defence strategy may be based on behavioural responses. For example, avoidance
      behaviour reduces contact with pathogens and thus the risk of infection as well
      as the requirement of immune system activation. Similarly, if pathogens are taken
      up orally, preferential feeding of pathogen-free food may be advantageous.
      Behavioural defences have been found in many animals, including the nematode
      Caenorhabditis elegans. We here tested nematodes from a laboratory based
      evolution experiment which had either coevolved with their microparasite Bacillus
      thuringiensis (BT) or evolved under control conditions. After 48 generations,
      coevolved populations were more sensitive to food conditions: in comparison with
      the controls, they reduced feeding activity in the presence of pathogenic BT
      strains while at the same time increasing it in the presence of non-pathogenic
      strains. We conclude that host-parasite coevolution can drive changes in the
      behavioural responsiveness to bacterial microbes, potentially leading to an
      increased defence against pathogens.

PMID- 21880623
TI  - Embryonic exposure to conspecific chemicals suppresses cane toad growth and
      survival.
AB  - Adaptations to suppress the viability of conspecifics may provide novel ways to
      control invasive taxa. The spread of cane toads (Rhinella marina) through
      tropical Australia has had severe ecological impacts, stimulating a search for
      biocontrol. Our experiments show that cane toad tadpoles produce waterborne
      chemical cues that suppress the viability of conspecifics encountering those cues
      during embryonic development. Brief (72 h) exposure to these cues in the egg and
      post-hatching phases massively reduced rates of survival and growth of larvae.
      Body sizes at metamorphosis (about three weeks later) were almost twice as great
      in control larvae as in tadpole-exposed larvae. The waterborne cue responsible
      for these effects might provide a weapon to reduce toad recruitment within the
      species' invaded range.

PMID- 21880624
TI  - Fostering the rebirth of natural history.
AB  - Natural history as we have known it is in decline. A growing movement is emerging
      across disciplines, to understand its decline, and nurture its rebirth. A network
      of like-minded scientists, resource managers, educators, writers and artists
      natural historians-recently convened four consecutive Natural History Initiative
      workshops to move past the forensic study of natural history, and instead focus
      on solutions, conspiring to identify opportunities that dovetail the practice of
      natural history with essential needs of modern science and society, and suggest
      ways forward. This series of workshops occurred at various locations in the
      western United States during the winter and spring of 2011, and recently
      culminated in a Synthesis Summit on 20-24 June 2011.

PMID- 21880626
TI  - 'YouTube': a useful tool for reminiscence therapy in dementia?

PMID- 21880625
TI  - RASSF1A and the BH3-only mimetic ABT-737 promote apoptosis in pediatric
      medulloblastoma cell lines.
AB  - The RASSF1A tumor suppressor is potentially the most important candidate gene
      identified in medulloblastoma to date, being epigenetically silenced in >79% of
      primary tumors. However, its functional role has not been previously addressed in
      this tumor type. Here, we demonstrate that expression of RASSF1A promotes the
      induction of cell death after activation of both the extrinsic and intrinsic
      apoptotic pathways in medulloblastoma cells. Treatment of UW228-3 cells stably
      expressing RASSF1A with an anti-CD95 antibody to induce extrinsic apoptosis and
      etoposide or cisplatin to activate intrinsic apoptosis augmented tumor cell
      killing in a caspase-dependent manner. This led to increased activation of the
      pro-apoptotic BCL-2 family member BAX. On the basis of this knowledge, we
      demonstrate how the loss of RASSF1A function in medulloblastoma cells might be
      overcome using the novel BH3-only mimetic ABT-737 in combination with
      chemotherapeutic agents to target the BCL-2 anti-apoptotic members. We show that
      ABT-737 increased susceptibility to apoptosis induced by DNA damage regardless of
      RASSF1A expression status through increased activation of BAX. Our findings
      identify the RASSF1A tumor suppressor as a promoter of apoptotic signaling
      pathways. Investigation of its mechanism of action has revealed that these
      pathways can still be promoted in its absence and how these potentially represent
      novel therapeutic targets for medulloblastoma.

PMID- 21880627
TI  - Diabetes, the glycaemic index and older people.

PMID- 21880628
TI  - Integrative nucleophosmin mutation-associated microRNA and gene expression
      pattern analysis identifies novel microRNA - target gene interactions in acute
      myeloid leukemia.
AB  - BACKGROUND: MicroRNAs are regulators of gene expression, which act mainly by
      decreasing mRNA levels of their multiple targets. Deregulated microRNA expression
      has been shown for acute myeloid leukemia, a disease also characterized by
      altered gene expression associated with distinct genomic aberrations such as
      nucleophosmin (NPM1) mutations. To shed further light on the role of deregulated
      microRNA and gene expression in cytogenetically normal acute myeloid leukemia
      with NPM1 mutation we performed an integrative analysis of microRNA and mRNA
      expression data sets. DESIGN AND METHODS: Both microRNA and gene expression
      profiles were investigated in samples from a cohort of adult cytogenetically
      normal acute myeloid leukemia patients (n=43; median age 46 years, range 23-60
      years) with known NPM1 mutation status (n=23 mutated, n=20 wild-type) and the
      data were integratively analyzed. Putative microRNA-mRNA interactions were
      validated by quantitative reverse transcriptase polymerase chain reaction,
      western blotting and luciferase reporter assays. For selected microRNAs,
      sensitivity of microRNA-overexpressing cells to cytarabine treatment was tested
      by FACS viability and cell proliferation assays. RESULTS: Our integrative
      approach of analyzing both microRNA- and gene expression profiles in parallel
      resulted in a refined list of putative target genes affected by NPM1 mutation
      associated microRNA deregulation. Of 177 putative microRNA - target mRNA
      interactions we identified and validated 77 novel candidates with known or
      potential involvement in leukemogenesis, such as IRF2-miR-20a, KIT-miR-20a and
      MN1-miR-15a. Furthermore, our data showed that deregulated expression of tumor
      suppressor microRNAs, such as miR-29a and miR-30c, might contribute to
      sensitivity to cytarabine, which is observed in NPM1 mutated acute myeloid
      leukemia. CONCLUSIONS: Overall, our observations highlight that integrative data
      analysis approaches can improve insights into leukemia biology, and lead to the
      identification of novel microRNA - target gene interactions of potential
      relevance for acute myeloid leukemia treatment.

PMID- 21880629
TI  - Cytopenias after day 28 in allogeneic hematopoietic cell transplantation: impact
      of recipient/donor factors, transplant conditions and myelotoxic drugs.
AB  - BACKGROUND: Secondary cytopenias are serious complications following
      hematopoietic cell transplantation. Etiologies include myelotoxic agents, viral
      infections, and possibly transplant-related factors such as the intensity of the
      conditioning regimen and the source of stem cells. DESIGN AND METHODS: We
      retrospectively analyzed data from 2162 hematopoietic cell transplant recipients
      to examine the effect of these factors on overall cytopenias occurring after 28
      days in hematopoietic cell transplantation. RESULTS: Advanced age of the patient,
      recipient cytomegalovirus seropositivity, unrelated donor status, human leukocyte
      antigen mismatch and lower doses of transplanted CD34(+) cells (<= 6.4*10(6)/kg)
      significantly increased the risk of cytopenias after day 28. Non-myeloablative
      hematopoietic cell transplantation had protective effects on anemia and
      thrombocytopenia after day 28 (adjusted odds ratio 0.76, probability value of
      0.05 and adjusted odds ratio 0.31, probability value of <0.0001, respectively)
      but not on overall or ganciclovir-related neutropenia. This lack of protection
      appeared to be due to the use of mycophenolate mofetil in the majority of
      recipients of non-myeloablative hematopoietic cell transplants. Peripheral blood
      stem cells did not confer protection from cytopenias when compared to bone
      marrow. CONCLUSIONS: Elderly patients appear to be more prone to cumulative
      toxicities of post-transplant drug regimens, but non-myeloablative conditioning,
      optimized human leukocyte antigen matching, and higher doses of CD34(+) cell
      infusions may reduce the risk of cytopenia after day 28.

PMID- 21880630
TI  - Minimal residual disease in peripheral blood at day 15 identifies a subgroup of
      childhood B-cell precursor acute lymphoblastic leukemia with superior prognosis.
AB  - BACKGROUND: Most minimal residual disease-directed treatment interventions in
      current treatment protocols for acute lymphoblastic leukemia are based on bone
      marrow testing, which is a consequence of previous studies showing the
      superiority of bone marrow over peripheral blood as an investigational material.
      Those studies typically did not explore the prognostic impact of peripheral blood
      involvement and lacked samples from very early time points of induction. DESIGN
      AND METHODS: In this study, we employed real-time quantitative polymerase chain
      reaction analysis to examine minimal residual disease in 398 pairs of blood and
      bone marrow follow-up samples taken from 95 children with B-cell precursor acute
      lymphoblastic leukemia treated with the ALL IC-BFM 2002 protocol. RESULTS: We
      confirmed the previously published poor correlation between minimal residual
      disease in blood and marrow at early treatment time points, with levels in bone
      marrow being higher than in blood in most samples (median 7.9-fold, range 0.04
      8,293-fold). A greater involvement of peripheral blood at diagnosis was
      associated with a higher white blood cell count at diagnosis (P=0.003) and with
      enlargement of the spleen (P=0.0004) and liver (P=0.05). At day 15, a level of
      minimal residual disease in blood lower than 10(-4) was associated with an
      excellent 5-year relapse-free survival in 78 investigated patients (100% versus
      69 +/- 7%; P=0.0003). Subgroups defined by the level of minimal residual disease
      in blood at day 15 (high-risk: >= 10(-2), intermediate-risk: <10(-2) and >= 10(
      4), standard-risk: <10(-4)) partially correlated with bone marrow-based
      stratification described previously, but the risk groups did not match
      completely. No other time point analyses were predictive of outcome in peripheral
      blood, except for a weak association at day 8. CONCLUSIONS: Minimal residual
      disease in peripheral blood at day 15 identified a large group of patients with
      an excellent prognosis and added prognostic information to the risk
      stratification based on minimal residual disease at day 33 and week 12.

PMID- 21880631
TI  - SWAP-70 regulates erythropoiesis by controlling alpha4 integrin.
AB  - Background The regulation of normal and stress-induced erythropoiesis is
      incompletely understood. Integrin-dependent adhesion plays important roles in
      erythropoiesis, but how integrins are regulated during erythropoiesis remains
      largely unknown. DESIGN AND METHODS: To obtain novel insights into the regulation
      of erythropoiesis, we used cellular and molecular approaches to analyze the role
      of SWAP-70 and the control of integrins through SWAP-70. In addition, mice
      deficient for this protein were investigated under normal and erythropoietic
      stress conditions. RESULTS: We show that SWAP-70, a protein involved in
      cytoskeletal F-actin rearrangements and integrin regulation in mast cells, is
      expressed in hematopoietic stem cells and myeloid-erythroid precursors. Although
      Swap-70(-/-) mice are not anemic, erythroblastic differentiation is perturbed,
      and SWAP-70 is required for an efficient erythropoietic stress response to acute
      anemia and for erythropoietic recovery after bone marrow transplantation in
      irradiated mice. SWAP-70 deficiency impairs colony-forming unit erythroid
      development, while burst-forming unit erythroid development is normal, and
      significantly affects development of late erythroblasts in the spleen and bone
      marrow. The alpha(4) integrin is constitutively hyper-activated in Swap-70(-/-)
      colony-forming unit erythroid cells, which hyper-adhere to fibronectin. Blocking
      alpha(4) and beta(1) integrin chains in vivo restored erythroblastic
      differentiation and the erythropoietic stress response in Swap-70(-/-) mice. 
      Conclusions Our study reveals that SWAP-70 is a novel regulator of integrin
      mediated red blood cell development and stress-induced erythropoiesis.

PMID- 21880633
TI  - Managing individuals with propensity to myeloid malignancies due to germline
      RUNX1 deficiency.

PMID- 21880632
TI  - The in vivo mechanism of action of CD20 monoclonal antibodies depends on local
      tumor burden.
AB  - BACKGROUND: CD20 monoclonal antibodies are widely used in clinical practice.
      Antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and
      direct cell death have been suggested to be important effector functions for CD20
      antibodies. However, their specific contributions to the in vivo mechanism of
      action of CD20 immunotherapy have not been well defined. DESIGN AND METHODS: Here
      we studied the in vivo mechanism of action of type I (rituximab and ofatumumab)
      and type II (HuMab-11B8) CD20 antibodies in a peritoneal, syngeneic, mouse model
      with EL4-CD20 cells using low and high tumor burden. RESULTS: Interestingly, we
      observed striking differences in the in vivo mechanism of action of CD20
      antibodies dependent on tumor load. In conditions of low tumor burden, complement
      was sufficient for tumor killing both for type I and type II CD20 antibodies. In
      contrast, in conditions of high tumor burden, activating FcgammaR (specifically
      FcgammaRIII), active complement and complement receptor 3 were all essential for
      tumor killing. Our data suggest that complement-enhanced antibody-dependent
      cellular cytotoxicity may critically affect tumor killing by CD20 antibodies in
      vivo. The type II CD20 antibody 11B8, which is a poor inducer of complement
      activation, was ineffective against high tumor burden. CONCLUSIONS: Tumor burden
      affects the in vivo mechanism of action of CD20 antibodies. Low tumor load can be
      eliminated by complement alone, whereas elimination of high tumor load requires
      multiple effector mechanisms.

PMID- 21880635
TI  - DNA methyltransferase 3a hot-spot locus is not mutated in pediatric patients
      affected by acute myeloid or T-cell acute lymphoblastic leukemia: an Italian
      study.

PMID- 21880636
TI  - Rare occurrence of DNMT3A mutations in myelodysplastic syndromes.
AB  - Gene mutations and epigenetic changes have been shown to play significant roles
      in the pathogenesis of myelodysplastic syndromes. Recently, mutations in DNMT3A
      were identified in 22.1% of patients with acute myeloid leukemia. In this study,
      we analyzed the frequency and clinical impact of DNMT3A mutations in a cohort of
      193 patients with myelodysplastic syndromes. Mutations in DNMT3A were found in
      2.6% of patients. The majority of mutations were heterozygous missense mutations
      affecting codon R882. Patients with DNMT3A mutations were found to have a higher
      rate of transformation to acute myeloid leukemia. When assessing the global
      methylation levels in patients with mutated versus unmutated DNMT3A and healthy
      controls no difference in global DNA methylation levels between the two groups
      was seen. Our data show that in patients with myelodysplastic syndromes, DNMT3A
      mutations occur at a low frequency and may be a risk factor for leukemia
      progression.

PMID- 21880634
TI  - Newly diagnosed immune thrombocytopenia in children and adults: a comparative
      prospective observational registry of the Intercontinental Cooperative Immune
      Thrombocytopenia Study Group.
AB  - BACKGROUND: Primary immune thrombocytopenia is a bleeding diathesis with an
      unknown etiology in predisposed individuals with immune disturbances. Although it
      is claimed that children and adults differ in clinical and laboratory aspects,
      few data exist to corroborate this observation. Our objective was to assess
      comparative data from children and adults with newly diagnosed immune
      thrombocytopenia. DESIGN AND METHODS: Clinical and laboratory data of 1,784
      children and 340 adults were extracted from the Pediatric and Adult Registry on
      Chronic Immune Thrombocytopenia. The registry represents a prospective cohort of
      children and adults with newly diagnosed immune thrombocytopenia. Participating
      investigators registered their patients immediately after the diagnosis using a
      web based data transfer. Children aged under 16 years were compared with adults
      aged 16 years and over with descriptive statistical analyses. RESULTS: The
      presenting mean platelet count of children and adults was 18.1 and 25.4 *
      10(9)/L. Signs of bleeding were reported in 24% of children and in 23% of adults,
      and intracranial hemorrhage in 10 of 1,784 children and in 6 of 340 adults. Co
      morbidity was observed in 3.9% of children and in 30% of adults. Bone marrow
      aspiration and laboratory tests (antinuclear antibodies, human immunodeficiency
      and hepatitis C virus) were performed more frequently in adults. Children and
      adults were followed with a 'watch and wait' strategy in 20% and in 29%,
      respectively. Immunoglobulins were used more frequently in children and
      corticosteroids in adults. CONCLUSIONS: Comparative data of children and adults
      with newly diagnosed immune thrombocytopenia revealed similarities in presenting
      platelet counts and in bleeding, whereas differences occurred in co-morbidity,
      diagnostic procedures and therapy.

PMID- 21880637
TI  - Mutations of PHF6 are associated with mutations of NOTCH1, JAK1 and rearrangement
      of SET-NUP214 in T-cell acute lymphoblastic leukemia.
AB  - BACKGROUND: Mutations in the PHF6 gene were recently described in patients with T
      cell acute lymphoblastic leukemia and in those with acute myeloid leukemia. The
      present study was designed to determine the prevalence of PHF6 gene alterations
      in T-cell acute lymphoblastic leukemia. DESIGN AND METHODS: We analyzed the
      incidence and prognostic value of PHF6 mutations in 96 Chinese patients with T
      cell acute lymphoblastic leukemia. PHF6 deletions were screened by real-time
      quantitative polymerase chain reaction and array-based comparative genomic
      hybridization. Patients were also investigated for NOTCH1, FBXW7, WT1, and JAK1
      mutations together with CALM-AF10, SET-NUP214, and SIL-TAL1 gene rearrangements.
      RESULTS: PHF6 mutations were identified in 11/59 (18.6%) adult and 2/37 (5.4%)
      pediatric cases of T-cell acute lymphoblastic leukemia, these incidences being
      significantly lower than those recently reported. Although PHF6 is X-linked and
      mutations have been reported to occur almost exclusively in male patients, we
      found no sex difference in the incidences of PHF6 mutations in Chinese patients
      with T-cell acute lymphoblastic leukemia. PHF6 deletions were detected in 2/79
      (2.5%) patients analyzed. NOTCH1 mutations, FBXW7 mutations, WT1 mutations, JAK1
      mutations, SIL-TAL1 fusions, SET-NUP214 fusions and CALM-AF10 fusions were
      present in 44/96 (45.8%), 9/96 (9.4%), 4/96 (4.1%), 3/49 (6.1%), 9/48 (18.8%),
      3/48 (6.3%) and 0/48 (0%) of patients, respectively. The molecular genetic
      markers most frequently associated with PHF6 mutations were NOTCH1 mutations
      (P=0.003), SET-NUP214 rearrangements (P=0.002), and JAK1 mutations (P=0.005). No
      differences in disease-free survival and overall survival between T-cell acute
      lymphoblastic leukemia patients with and without PHF6 mutations were observed in
      a short-term follow-up. CONCLUSIONS: Overall, these results indicate that, in T
      cell acute lymphoblastic leukemia, PHF6 mutations are a recurrent genetic
      abnormality associated with mutations of NOTCH1, JAK1 and rearrangement of SET
      NUP214.

PMID- 21880638
TI  - Acute myeloid leukemia with expanded erythropoiesis.

PMID- 21880639
TI  - Follicular lymphoma grade 3B: is it a real disease?

PMID- 21880640
TI  - Can multiple myeloma become a curable disease?

PMID- 21880641
TI  - Graft-versus-host disease therapy: something else beyond glucocorticoids?

PMID- 21880642
TI  - High pentraxin 3 level predicts septic shock and bacteremia at the onset of
      febrile neutropenia after intensive chemotherapy of hematologic patients.
AB  - We evaluated pentraxin 3 as a marker for complications of neutropenic fever in
      100 hematologic patients receiving intensive chemotherapy. Pentraxin 3 and C
      reactive protein were measured at fever onset and then daily to day 3. Bacteremia
      was observed in 19 patients and septic shock in 5 patients (three deaths). In
      comparison to C-reactive protein, pentraxin 3 achieved its maximum more rapidly.
      Pentraxin 3 correlated not only with the same day C-reactive protein but also
      with the next day C-reactive protein. High pentraxin 3 on day 0 was associated
      with the development of septic shock (P=0.009) and bacteremia (P=0.046). The non
      survivors had constantly high pentraxin 3 levels. To conclude, pentraxin 3 is an
      early predictor of complications in hematologic patients with neutropenic fever.
      High level of pentraxin 3 predicts septic shock and bacteremia already at the
      onset of febrile neutropenia. (ClinicalTrials.gov Identifier: NCT00781040.).

PMID- 21880643
TI  - Ilya Metchnikoff, the phagocytic theory, and how things often work in science.

PMID- 21880644
TI  - The double life of M-ficolin: what functions when circulating in serum and
      tethered to leukocyte surfaces?

PMID- 21880645
TI  - Welfare state regimes, infant mortality and life expectancy: integrating evidence
      from East Asia.
AB  - BACKGROUND: This longitudinal study builds on the cross-sectional work of Karim
      et al and examines the influence of welfare state regime on population health
      with a particular focus on East Asian welfare states (eg, Hong Kong, Japan,
      Korea, Singapore and Taiwan). METHODS: Data were extracted from the Organisation
      of Economic Co-operation and Development Data Set, World Development Indicators
      and Asian Development Bank's key indicators from 1980 to 2006. Infant mortalities
      and life expectancy were used as health-outcome varables. Thirty-one countries
      were categorised into six types of welfare regimes: Scandinavian, Anglo-Saxon,
      Bismarckian, Southern, Eastern European and East Asian. Mixed models were applied
      to analyse the data with repeated measurements. RESULTS: In keeping with Karim et
      al, Scandinavian and Eastern European welfare states have lower and higher infant
      mortalities respectively compared with East Asian welfare states. Eastern
      European welfare states had a lower life expectancy than East Asian welfare
      states. Most welfare states had a higher social, health and education
      expenditure, and higher densities of physicians than East Asian welfare states.
      CONCLUSION: East Asian welfare states did not have worse health than most welfare
      states. Future studies should continue to incorporate East Asian countries in the
      typology of welfare regimes that include more social, economic, political and
      healthcare system characteristic variables to provide insight on the mechanism by
      which welfare-state regimes influence population health.

PMID- 21880646
TI  - Assessing the patient safety competencies of healthcare professionals: a
      systematic review.
AB  - Background Patient safety training of healthcare professionals is a new area of
      education. Assessment of the pertinent competencies should be a part of this
      education. This review aims to identify the available assessment tools for
      different patient safety domains and evaluate them according to Miller's four
      competency levels.  Methods The authors searched PubMed, MEDLINE, the Cumulative
      Index to Nursing and Allied Health Literature (CINAHL), Web of Science, psycINFO
      and the Education Resource Information Center (ERIC) from the start of each
      database to December 2010 for English-language articles that evaluated or
      described tools for the assessment of the safety competencies of individual
      medical and/or nursing professionals. Reports on the assessment of technical,
      clinical, medication and disclosure skills were excluded.  Results Thirty-four
      assessment tools in 48 studies were identified: 20 tools for medical
      professionals, nine tools for nursing professionals, and five tools for both
      medical and nursing professionals. Twenty of these tools assessed the two highest
      Miller levels ('shows how' and 'does') and four tools were directed at multiple
      levels. Most of the tools that aimed at the higher levels assessed the skills of
      working in teams (17 tools), risk management (15 tools), and communication (11
      tools). Internal structure (reliability, 22 tools) and content validity (14
      tools) when described were found to be moderate. Only a small number of tools
      addressed the relationship between the tool itself and (1) other assessments
      (concurrent, predictive validity, eight tools), and (2) educational outcomes
      (seven tools).  Conclusions There are many tools designed to assess the safety
      competencies of healthcare professionals. However, a reliable and valid toolbox
      for summative testing that covers all patient safety domains at Miller's four
      competency levels cannot yet be constructed. Many tools, however, are useful for
      formative feedback.

PMID- 21880647
TI  - Gender equality in India for children with congenital heart disease: looking for
      answers.

PMID- 21880648
TI  - Cocaine and the heart: more than just coronary disease.

PMID- 21880649
TI  - Mild chronic kidney disease is an independent predictor of long-term mortality
      after emergency angiography and primary percutaneous intervention in patients
      with ST-elevation myocardial infarction.
AB  - OBJECTIVE: Moderate renal impairment (RI) with a glomerular filtration rate (GFR)
      <60 ml/min/1.73 m2 is known to predict survival. The authors investigated whether
      mild RI with an estimated GFR of 60-89 ml/min/1.73 m2 independently predicts
      survival in a contemporary population with ST segment elevation myocardial
      infarction (STEMI). DESIGN: This is a single-centre, observational, retrospective
      cohort study. Patients 601 patients with STEMI who underwent emergency catheter
      laboratory admission met the inclusion criteria for this study. METHODS:
      Estimated glomerular filtration rate (eGFR) was obtained by the Modified Diet in
      Renal Disease equation, and preprocedure renal function was subdivided into
      chronic kidney disease stages. Univariate and multivariate Cox regression
      analyses were performed to assess which of 17 patient or procedural variables
      were independent risk factors for death. RESULTS: Longitudinal data were collated
      for 576 patients (96.3%). Median follow-up time was 2.6 years. 30-day and long
      term death rates were 5.7% and 12.5%, respectively. Following multivariable
      analysis, mild RI with an eGFR of 60-89 ml/min/1.73 m2 was a strong independent
      predictor of death, compared with an eGFR >=90 ml/min/1.73 m2 (HR 2.79, 95% CI
      1.98 to 3.92, p<0.001), and increasing chronic kidney disease stage was a strong
      predictor of death after both 30 days and long-term follow-up. An eGFR of 60-89
      ml/min/1.73 m2 had a greater independent effect on short- and long-term mortality
      than the presence of diabetes mellitus (HR 2.0, 95% CI 1.2 to 3.33). CONCLUSION:
      Mild RI (eGFR=60-89 ml/min/1.73 m2) on admission is strongly predictive of short-
      and long-term mortality in patients with STEMI admitted to the catheter
      laboratory. A redefined threshold of clinically significant impairment is now
      required (GFR<90 ml/min/1.73 m2).

PMID- 21880650
TI  - Optimisation of atrioventricular delay during exercise improves cardiac output in
      patients stabilised with cardiac resynchronisation therapy.
AB  - BACKGROUND: Atrioventricular (AV) delay in cardiac resynchronisation therapy
      (CRT) recipients are typically optimised at rest. However, there are limited data
      on the impact of exercise-induced changes in heart rate on the optimal AV delay
      and left ventricular function. METHODS AND RESULTS: The authors serially
      programmed AV delays in 41 CRT patients with intrinsic sinus rhythm at rest and
      during two stages of supine bicycle exercise with heart rates at 20 bpm (stage I)
      and 40 bpm (stage II) above baseline. The optimal AV delay during exercise was
      determined by the iterative method to maximise cardiac output using Doppler
      echocardiography. Results were compared to physiological change in PR intervals
      in 56 normal controls during treadmill exercise. The optimal AV delay was
      progressively shortened (p<0.05) with escalating exercise level (baseline: 123+/
      26 ms vs. stage I: 102+/-24 ms vs stage II: 70+/-22 ms, p<0.05). AV delay
      optimisation led to a significantly higher cardiac output than without
      optimisation did during stage I (6.2+/-1.2 l/min vs. 5.2+/-1.2 l/min, p<0.001)
      and stage II (6.8+/-1.6 l/min vs. 5.9+/-1.3 l/min, p<0.001) exercise. A linear
      inverse relationship existed between optimal AV delays and heart rates in CRT
      patients (AV delay=241-1.61*heart rate, R2=0.639, p<0.001) and healthy controls
      (R2=0.646, p<0.001), but the slope of regression was significantly steeper in CRT
      patients (p<0.001). CONCLUSIONS: Haemodynamically optimal AV delay shortened
      progressively with increasing heart rate during exercise, which suggests the need
      for programming of rate-adaptive AV delay in CRT recipients.

PMID- 21880651
TI  - Routine use of the transradial approach in primary percutaneous coronary
      intervention: procedural aspects and outcomes in 2209 patients treated in a
      single high-volume centre.
AB  - OBJECTIVE: To examine the feasibility of a routine transradial approach (TRA) in
      primary percutaneous coronary intervention (PPCI) for acute ST-segment elevation
      myocardial infarction (STEMI). DESIGN: A single-centre observational study with
      prospective data collection. SETTING: A high-volume interventional centre in
      Amsterdam, The Netherlands. PATIENTS: Procedural data were analysed for 2209
      consecutive patients presenting with STEMI without cardiogenic shock, between
      January 2001 and December 2008. INTERVENTIONS: PPCI routinely performed by the
      TRA. MAIN OUTCOME MEASURES: The primary outcomes of interest were the need for
      crossover to another vascular access site, the achievement of procedural success
      and their trends over time. Secondary outcome measures were trends in total
      procedural duration, fluoroscopy times and use of equipment. RESULTS: In a total
      of 2209 procedures the radial artery was the primary access site, comprising
      96.1% of all procedures performed during the study period. In 84 cases (3.8%)
      access site crossover was needed. Crossover rates decreased from 5.9% in 2001-2
      to 1.5% in 2007-8 (p=0.001). The procedural success rate was 94.1%, which
      remained stable over the years. Despite an increased complexity of PPCI (more non
      left anterior descending infarct-related arteries, thrombus aspiration and
      multivessel PPCI), total procedural duration decreased from 38 min (IQR 28-50) in
      2001-2 to 24 min (18-33) in 2007-8, p<0.001 for trend. CONCLUSIONS: Systematic
      use of the TRA in PPCI yields low access site crossover, high procedural success
      rates and excellent procedural performances. It can therefore represent the
      primary access site in the vast majority of STEMI patients.

PMID- 21880652
TI  - Risk of ST versus non-ST elevation myocardial infarction associated with non
      steroidal anti-inflammatory drugs.
AB  - OBJECTIVE: The objective of this study was to explore the association of non
      steroidal anti-inflammatory drugs (NSAID) with ST-segment elevation myocardial
      infarction (STEMI) and non-ST segment elevation myocardial infarction (NSTEMI).
      DESIGN, SETTING & PATIENTS: A matched case-control study comparing patients with
      incident non-fatal myocardial infarction (MI) collected by cardiologists with
      controls. Cases were retrieved from the Pharmacoepidemiological General Research
      on Myocardial Infarction (PGRx-MI) registry, a French nationwide registry
      consisting of 55 cardiology centres, whereas controls were selected from general
      practice settings. Both cases and controls were recruited from the same
      geographically diverse areas across continental France. MAIN OUTCOME MEASURES:
      The association between NSAID and MI was assessed by matched adjusted OR from
      conditional logistic regression. RESULTS: Between 2007 and 2009, 1125 incident
      cases were included (67.3% and 32.7% for STEMI and NSTEMI, respectively), with
      2790 controls matched to MI cases by age and sex. Current use (previous 2 months)
      of either diclofenac or naproxen and other arylpropionic acid NSAID was not
      associated with STEMI (OR 0.9, 95% CI 0.4 to 1.9 and OR 1.0, 95% CI 0.6 to 1.7,
      respectively), instead it showed significant association with NSTEMI (OR 2.8, 95%
      CI 1.2 to 6.4 and OR 0.4, 95% CI 0.2 to 0.9, respectively). Our study confirms
      results from previously published analyses on the association of MI with NSAID
      (OR 1.5, 0.9, and 1.0 for diclofenac, naproxen and related NSAID, and all NSAID
      combined, respectively). CONCLUSIONS: Our study shows that the MI risk
      modification associated with NSAID is limited to NSTEMI.

PMID- 21880653
TI  - Physiological cardiac remodelling in response to endurance exercise training:
      cellular and molecular mechanisms.
AB  - Exercise training fosters the health and performance of the cardiovascular
      system, and represents nowadays a powerful tool for cardiovascular therapy.
      Exercise exerts its beneficial effects through reducing cardiovascular risk
      factors, and directly affecting the cellular and molecular remodelling of the
      heart. Traditionally, moderate endurance exercise training has been viewed to
      determine a balanced and revertible physiological growth, through cardiomyocyte
      hypertrophy accompanied by appropriate neoangiogenesis (the Athlete's Heart).
      These cellular adaptations are due to the activation of signalling pathways and
      in particular, the IGF-1/IGF-1R/Akt axis appears to have a major role. Recently,
      it has been shown that physical exercise determines cardiac growth also through
      new cardiomyocyte formation. Accordingly, burgeoning evidence indicates that
      exercise training activates circulating, as well as resident tissue-specific
      cardiac, stem/progenitor cells. Dissecting the mechanisms for stem/progenitor
      cell activation with exercise will be instrumental to devise new effective
      therapies, encompassing myocardial regeneration for a large spectrum of
      cardiovascular diseases.

PMID- 21880654
TI  - Supine-exercise-induced oxygen supply to the right myocardium is attenuated in
      patients with severe idiopathic pulmonary arterial hypertension.
AB  - BACKGROUND: Impaired right ventricular (RV) myocardial blood flow (MBF) has been
      associated with RV dysfunction and fatal RV failure in idiopathic pulmonary
      hypertension during stress. MBF and O(2) extraction from myocardial capillaries
      (O(2) extraction fraction (OEF)) influence myocardial O(2) supply. OBJECTIVE: To
      determine how the baseline RV OEF affects the amount of MBF increase induced by
      supine exercise, the authors hypothesise that higher baseline OEF (H-OEF) results
      in limited O(2) extraction during exercise and that MBF must therefore be
      increased to obtain sufficient O(2). METHODS: In 18 patients with idiopathic
      pulmonary hypertension, baseline OEF, resting MBF and exercise-induced MBF at 40%
      of maximal cardiopulmonary exercise testing load were measured using positron
      emission tomography and [(15)O]O(2), [(15)O]H(2)O and [(15)O]CO. RESULTS: For the
      whole population, exercise increased RV MBF from 0.68+/-0.16 to 1.13 +/- 0.38
      ml/min/g (p < 0.0001). The MBF exercise-to-rest ratio (reserve) was 1.7 +/- 0.7.
      The median baseline OEF was 0.73 at which the patient population was split into H
      OEF and lower baseline OEF (L-OEF). Baseline MBF values (0.61 +/- 0.11 and 0.74
      +/- 0.17 ml/min/g, respectively) were similar, and exercise induced a significant
      MBF increase in both groups (p = 0.0001). However, exercise-induced increase in
      MBF was significantly less in the H-OEF group than in the L-OEF group (0.97 +/-
      0.30 and 1.30 +/- 0.39 ml/min/g, respectively, p < 0.05). Moreover, H-OEF
      patients had lower baseline stroke volume and cardiac output than the L-OEF group
      (52 +/- 19 ml and 4.0 +/- 1.1 l/min vs 78 +/- 18 ml and 5.5 +/- 0.9 l/min,
      respectively, both p < 0.05). CONCLUSIONS: H-OEF patients were hemodynamically
      poorer and showed a lower exercise-induced MBF increase compared to L-OEF
      patients, suggesting exercise-induced O(2) supply limitation.

PMID- 21880655
TI  - Detection of very early stent healing after primary angioplasty: an optical
      coherence tomographic observational study of chromium cobaltum and first
      generation drug-eluting stents. The DETECTIVE study.
AB  - BACKGROUND: Lack of stent coverage appears to be associated with stent
      thrombosis, a problem of particular concern in patients with ST elevation
      myocardial infarction (STEMI). METHODS: The DETECTIVE European Multicenter
      Registry was set up to address the early modality of stent healing in the setting
      of STEMI. The Registry compared, with an early optical coherence tomography (OCT)
      evaluation performed at 3-7 days, the patterns of coverage and apposition of the
      first generation of drug-eluting stents (DESs) and cobalt chromium non-drug
      eluting stents (CCSs) that were deployed in culprit lesions and in non-culprit
      segments. The Registry included only patients with a multi-vessel disease to
      allow, at 3-7 days from the first angioplasty, a deferred OCT examination and a
      staged intervention in another vessel. RESULTS: 28 stented lesions (15 patients)
      eventually entered the final OCT assessment. 13 stents were first-generation
      DESs, while the remaining 15 were CCSs. 18 stents (64%) were deployed at culprit
      STEMI lesions, and the remaining 10 (36%) were deployed at non-culprit sites. The
      distribution of clinical and procedural variables in DES and CCS as well as in
      culprit and non-culprit sites was not different. In total, 27,019 struts were
      analysed in 28 stents. The percentage of stent uncoverage in the overall analysis
      was 11.7%, while the percentage of malapposition and that of struts covered with
      thrombus were 4.8% and 2.2%, respectively. A low percentage of strut uncoverage
      was found in all the four studied subgroups: DES 12.8%, CCS 10.9%, stents
      deployed in culprit lesions 13.2% and stents deployed in non-culprit lesions
      8.7%. CONCLUSIONS: In conclusion, our data show that in patients with STEMI, a
      very high percentage of stent struts is covered by an early thin rim of tissue
      within 7 days after stent positioning. The present data bring new insights in the
      mechanism and timing of strut coverage.

PMID- 21880656
TI  - In vivo imaging and noninvasive ablation of pyramidal neurons in adult NEX
      CreERT2 mice.
AB  - To study the function of individual neurons that are embedded in a complex neural
      network is difficult in mice. Conditional mutagenesis permits the spatiotemporal
      control of gene expression including the ablation of cells by toxins. To direct
      expression of a tamoxifen-inducible variant of Cre recombinase (CreERT2)
      selectively to cortical neurons, we replaced the coding region of the murine Nex1
      gene by CreERT2 cDNA via homologous recombination in embryonic stem cells. When
      injected with tamoxifen, adult NEX-CreERT2 mice induced reporter gene expression
      exclusively in projection neurons of the neocortex and hippocampus. By titrating
      the tamoxifen dosage, we achieved recombination in single cells, which allowed
      multiphoton imaging of neocortical neurons in live mice. When hippocampal
      projection neurons were genetically ablated by induced expression of diphteria
      toxin, within 20 days the inflammatory response included the infiltration of CD3+
      T cells. This marks a striking difference from similar studies, in which dying
      oligodendrocytes failed to recruit cells of the adaptive immune system.

PMID- 21880657
TI  - Somatic hybrid plants of Nicotiana x sanderae (+) N. debneyi with fungal
      resistance to Peronospora tabacina.
AB  - BACKGROUND AND AIMS: The genus Nicotiana includes diploid and tetraploid species,
      with complementary ecological, agronomic and commercial characteristics. The
      species are of economic value for tobacco, as ornamentals, and for secondary
      plant-product biosynthesis. They show substantial differences in disease
      resistance because of their range of secondary products. In the last decade,
      sexual hybridization and transgenic technologies have tended to eclipse
      protoplast fusion for gene transfer. Somatic hybridization was exploited in the
      present investigation to generate a new hybrid combination involving two sexually
      incompatible tetraploid species. The somatic hybrid plants were characterized
      using molecular, molecular cytogenetic and phenotypic approaches. METHODS:
      Mesophyll protoplasts of the wild fungus-resistant species N. debneyi (2n = 4x =
      48) were electrofused with those of the ornamental interspecific sexual hybrid N.
      * sanderae (2n = 2x = 18). From 1570 protoplast-derived cell colonies selected
      manually in five experiments, 580 tissues were sub-cultured to shoot regeneration
      medium. Regenerated plants were transferred to the glasshouse and screened for
      their morphology, chromosomal composition and disease resistance. KEY RESULTS:
      Eighty-nine regenerated plants flowered; five were confirmed as somatic hybrids
      by their intermediate morphology compared with parental plants, cytological
      constitution and DNA-marker analysis. Somatic hybrid plants had chromosome
      complements of 60 or 62. Chromosomes were identified to parental genomes by
      genomic in situ hybridization and included all 18 chromosomes from N. * sanderae,
      and 42 or 44 chromosomes from N. debneyi. Four or six chromosomes of one
      ancestral genome of N. debneyi were eliminated during culture of electrofusion
      treated protoplasts and plant regeneration. Both chloroplasts and mitochondria of
      the somatic hybrid plants were probably derived from N. debneyi. All somatic
      hybrid plants were fertile. In contrast to parental plants of N. * sanderae, the
      seed progeny of somatic hybrid plants were resistant to infection by Peronospora
      tabacina, a trait introgressed from the wild parent, N. debneyi. CONCLUSIONS:
      Sexual incompatibility between N. * sanderae and N. debneyi was circumvented by
      somatic hybridization involving protoplast fusion. Asymmetrical nuclear hybridity
      was seen in the hybrids with loss of chromosomes, although importantly, somatic
      hybrids were fertile and stable. Expression of fungal resistance makes these
      somatic hybrids extremely valuable germplasm in future breeding programmes in
      ornamental tobacco.

PMID- 21880659
TI  - Allotetraploid origin and divergence in Eleusine (Chloridoideae, Poaceae):
      evidence from low-copy nuclear gene phylogenies and a plastid gene chronogram.
AB  - BACKGROUND AND AIMS: Eleusine (Poaceae) is a small genus of the subfamily
      Chloridoideae exhibiting considerable morphological and ecological diversity in
      East Africa and the Americas. The interspecific phylogenetic relationships of
      Eleusine are investigated in order to identify its allotetraploid origin, and a
      chronogram is estimated to infer temporal relationships between palaeoenvironment
      changes and divergence of Eleusine in East Africa. METHODS: Two low-copy nuclear
      (LCN) markers, Pepc4 and EF-1alpha, were analysed using parsimony, likelihood and
      Bayesian approaches. A chronogram of Eleusine was inferred from a combined data
      set of six plastid DNA markers (ndhA intron, ndhF, rps16-trnK, rps16 intron,
      rps3, and rpl32-trnL) using the Bayesian dating method. KEY RESULTS: The
      monophyly of Eleusine is strongly supported by sequence data from two LCN
      markers. In the cpDNA phylogeny, three tetraploid species (E. africana, E.
      coracana and E. kigeziensis) share a common ancestor with the E. indica-E.
      tristachya clade, which is considered a source of maternal parents for
      allotetraploids. Two homoeologous loci are isolated from three tetraploid species
      in the Pepc4 phylogeny, and the maternal parents receive further support. The A
      type EF-1alpha sequences possess three characters, i.e. a large number of
      variations of intron 2; clade E-A distantly diverged from clade E-B and other
      diploid species; and seven deletions in intron 2, implying a possible derivation
      through a gene duplication event. The crown age of Eleusine and the
      allotetraploid lineage are 3.89 million years ago (mya) and 1.40 mya,
      respectively. CONCLUSIONS: The molecular data support independent allotetraploid
      origins for E. kigeziensis and the E. africana-E. coracana clade. Both events may
      have involved diploids E. indica and E. tristachya as the maternal parents, but
      the paternal parents remain unidentified. The habitat-specific hypothesis is
      proposed to explain the divergence of Eleusine and its allotetraploid lineage.

PMID- 21880658
TI  - Flavonols: old compounds for old roles.
AB  - BACKGROUND: New roles for flavonoids, as developmental regulators and/or
      signalling molecules, have recently been proposed in eukaryotic cells exposed to
      a wide range of environmental stimuli. In plants, these functions are actually
      restricted to flavonols, the ancient and widespread class of flavonoids. In
      mosses and liverworts, the whole set of genes for flavonol biosynthesis - CHS,
      CHI, F3H, FLS and F3'H - has been detected. The flavonol branch pathway has
      remained intact for millions of years, and is almost exclusively involved in the
      responses of plants to a wide array of stressful agents, despite the fact that
      evolution of flavonoid metabolism has produced >10 000 structures. SCOPE: Here
      the emerging functional roles of flavonoids in the responses of present-day
      plants to different stresses are discussed based on early, authoritative views of
      their primary functions during the colonization of land by plants. Flavonols are
      not as efficient as other secondary metabolites in absorbing wavelengths in the
      290-320 nm spectral region, but display the greatest potential to keep stress
      induced changes in cellular reactive oxygen species homeostasis under control,
      and to regulate the development of individual organs and the whole plant. Very
      low flavonol concentrations, as probably occurred in early terrestrial plants,
      may fully accomplish these regulatory functions. CONCLUSIONS: During the last two
      decades the routine use of genomic, chromatography/mass spectrometry and
      fluorescence microimaging techniques has provided new insights into the
      regulation of flavonol metabolism as well as on the inter- and intracellular
      distribution of stress-responsive flavonols. These findings offer new evidence on
      how flavonols may have performed a wide array of functional roles during the
      colonization of land by plants. In our opinion this ancient flavonoid class is
      still playing the same old and robust roles in present-day plants.

PMID- 21880660
TI  - Effects of floral display size on male and female reproductive success in Mimulus
      ringens.
AB  - BACKGROUND AND AIMS: The number of flowers blooming simultaneously on a plant may
      have profound consequences for reproductive success. Large floral displays often
      attract more pollinator visits, increasing outcross pollen receipt. However,
      pollinators frequently probe more flowers in sequence on large displays,
      potentially increasing self-pollination and reducing pollen export per flower. To
      better understand how floral display size influences male and female fitness, we
      manipulated display phenotypes and then used paternity analysis to quantify
      siring success and selfing rates. METHODS: To facilitate unambiguous assignment
      of paternity, we established four replicate (cloned) arrays of Mimulus ringens,
      each consisting of genets with unique combinations of homozygous marker
      genotypes. In each array, we trimmed displays to two, four, eight or 16 flowers.
      When fruits ripened, we counted the number of seeds per fruit and assigned
      paternity to 1935 progeny. KEY RESULTS: Siring success per flower declined
      sharply with increasing display size, while female success per flower did not
      vary with display. The rate of self-fertilization increased for large floral
      displays, but siring losses due to geitonogamous pollen discounting were much
      greater than siring gains through increased self-fertilization. As display size
      increased, each additional seed sired through geitonogamous self-pollination was
      associated with a loss of 9.7 seeds sired through outcrossing. CONCLUSIONS:
      Although total fitness increased with floral display size, the marginal return on
      each additional flower declined steadily as display size increased. Therefore, a
      plant could maximize fitness by producing small displays over a long flowering
      period, rather than large displays over a brief flowering period.

PMID- 21880661
TI  - Eco-geographically divergent diploids, Caucasian clover (Trifolium ambiguum) and
      western clover (T. occidentale), retain most requirements for hybridization.
AB  - BACKGROUND AND AIMS: DNA sequence similarities and hybridization patterns in
      Trifolium (clovers) section Trifoliastrum suggest that rapid radiation from a
      common ancestral source led to this complex of diverse species distributed across
      Europe, western Asia and North Africa. Two of the most geographically and
      ecologically divergent of these species are the rhizomatous T. ambiguum from high
      altitudes in eastern Europe and western Asia and the stoloniferous T. occidentale
      from sea level in western Europe. Attempts were made to hybridize these species
      to ascertain whether, despite this separation, gene flow could be achieved,
      indicating the retention of the genetic factors necessary for hybridization.
      METHODS: Three F(1) hybrids formed after embryo rescue were described,
      characterized by conventional and molecular cytogenetics, subjected to fertility
      tests and progeny generations were developed. RESULTS AND CONCLUSIONS: Partially
      fertile hybrids between Trifolium ambiguum and T. occidentale were obtained for
      the first time. The F(1) hybrids produced seeds after open-pollination, and also
      produced triploid progeny in backcrosses to T. occidentale from the functioning
      of unreduced gametes in the hybrids. These plants were fertile and produced
      progeny with T. occidentale and with T. repens. Meiotic chromosome pairing in the
      F(1) showed six to eight bivalents per pollen mother cell, indicating pairing
      between the parental genomes. A chromosome-doubled form of one hybrid, produced
      using colchicine, showed some multivalents, indicative of interspecific
      chromosome pairing. The hybrid plants were robust and combined phenotypic
      characteristics of both species, having stolons, thick roots and a few rhizomes.
      Results show that despite separation by the entire breadth of Europe, the
      speciation process is incomplete, and these taxa have partially retained most of
      the genetic compatibilities needed for hybridization (possibly except for
      endosperm development, which was not tested). The fertile progeny populations
      could lead to new clover breeding strategies based on new hybrid forms.

PMID- 21880662
TI  - Safeguarding public health, the core reason for solid waste management.

PMID- 21880663
TI  - Sustainable sanitary landfill celebrates its 80th anniversary.

PMID- 21880666
TI  - The ADAMTS(L) family and human genetic disorders.
AB  - ADAMTS designates a family of 19 secreted enzymes, whose the first member ADAMTS1
      was described in 1997. The ADAMTS family has a role in extracellular matrix
      degradation and turn over and has previously been involved in various human
      biological processes, including connective tissue structure, cancer, coagulation,
      arthritis, angiogenesis and cell migration. More recently, the ADAMTS(L) family
      has been described, sharing the same ancillary domain but distinct by the absence
      of any enzyme activity. Mutations in ADAMTS13, ADAMTS2, ADAMTS10, ADAMTS17,
      ADAMTSL2 and ADAMTSL4 have been identified in distinct human genetic disorders
      ranging from thrombotic thrombocytopenic purpura to acromelic dysplasia. The aim
      of our review was to emphasize the role of this family in the extracellular
      matrix based on human phenotypes so far identified in relation with ADAMTS(L)
      mutations.

PMID- 21880664
TI  - Restrictive loss of plakoglobin in cardiomyocytes leads to arrhythmogenic
      cardiomyopathy.
AB  - Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inheritable
      myocardial disorder associated with fibrofatty replacement of myocardium and
      ventricular arrhythmia. A subset of ARVC is categorized as Naxos disease, which
      is characterized by ARVC and a cutaneous disorder. A homozygous loss-of-function
      mutation of the Plakoglobin (Jup) gene, which encodes a major component of the
      desmosome and the adherens junction, had been identified in Naxos patients,
      although the underlying mechanism remained elusive. We generated Jup mutant mice
      by ablating Jup in cardiomyocytes. Jup mutant mice largely recapitulated the
      clinical manifestation of human ARVC: ventricular dilation and aneurysm, cardiac
      fibrosis, cardiac dysfunction and spontaneous ventricular arrhythmias. Ultra
      structural analyses revealed that desmosomes were absent in Jup mutant myocardia,
      whereas adherens junctions and gap junctions were preserved. We found that
      ventricular arrhythmias were associated with progressive cardiomyopathy and
      fibrosis in Jup mutant hearts. Massive cell death contributed to the
      cardiomyocyte dropout in Jup mutant hearts. Despite the increase of beta-catenin
      at adherens junctions in Jup mutant cardiomyoicytes, the Wnt/beta-catenin
      mediated signaling was not altered. Transforming growth factor-beta-mediated
      signaling was found significantly elevated in Jup mutant cardiomyocytes at the
      early stage of cardiomyopathy, suggesting an important pathogenic pathway for Jup
      related ARVC. These findings have provided further insights for the pathogenesis
      of ARVC and potential therapeutic interventions.

PMID- 21880665
TI  - Gene therapy using self-complementary Y733F capsid mutant AAV2/8 restores vision
      in a model of early onset Leber congenital amaurosis.
AB  - Defects in the photoreceptor-specific gene aryl hydrocarbon receptor interacting
      protein-like 1 (Aipl1) are associated with Leber congenital amaurosis (LCA), a
      childhood blinding disease with early-onset retinal degeneration and vision loss.
      Furthermore, Aipl1 defects are characterized at the most severe end of the LCA
      spectrum. The rapid photoreceptor degeneration and vision loss observed in the
      LCA patient population are mimicked in a mouse model lacking AIPL1. Using this
      model, we evaluated if gene replacement therapy using recent advancements in
      adeno-associated viral vectors (AAV) provides advantages in preventing rapid
      retinal degeneration. Specifically, we demonstrated that the novel self
      complementary Y733F capsid mutant AAV2/8 (sc-Y733F-AAV) provided greater
      preservation of photoreceptors and functional vision in Aipl1 null mice compared
      with single-stranded AAV2/8. The benefits of sc-Y733F-AAV were evident following
      viral administration during the active phase of retinal degeneration, where only
      sc-Y733F-AAV treatment achieved functional vision rescue. This result was likely
      due to higher and earlier onset of Aipl1 expression. Based on our studies, we
      conclude that the sc-Y733F-AAV2/8 viral vector, to date, achieves the best rescue
      for rapid retinal degeneration in Aipl1 null mice. Our results provide important
      considerations for viral vectors to be used in future gene therapy clinical
      trials targeting a wider severity spectrum of inherited retinal dystrophies.

PMID- 21880667
TI  - EPA's proposed biotech policy turns a deaf ear to science.

PMID- 21880668
TI  - To infinity ... and beyond! Human spaceflight and life science.

PMID- 21880670
TI  - RAAS Working Group Update. Editorial.

PMID- 21880669
TI  - Novel O-linked glycans containing 6'-sulfo-Gal/GalNAc of MUC1 secreted from human
      breast cancer YMB-S cells: possible carbohydrate epitopes of KL-6(MUC1)
      monoclonal antibody.
AB  - Human serum Krebs von den Lugen-6 (KL-6) antigen is a MUC1 glycoprotein (KL
      6/MUC1) recognized by anti-KL-6 monoclonal antibody (KL-6/mAb) and has been
      utilized as a diagnostic marker for interstitial pneumonia. KL-6/mAb is thought
      to recognize the specific glycopeptides sequence of MUC1, but the precise glycan
      structure of the epitope is unclear. In this study, we determined the
      carbohydrate structures of KL-6/MUC1 to search the carbohydrate epitopes for KL
      6/mAb. KL-6/MUC1 was purified from the culture medium of human breast cancer YMB
      S cells by KL-6/mAb-affinity chromatography; the O-linked glycan structures were
      determined in combination with paper electrophoresis, several lectin column
      chromatographies, sialidase digestion and methanolysis. KL-6/MUC1 contained core
      1 and extended core 1 glycans modified with one or two sialic acid/sulfate
      residues. Based on these structures, several synthetic glycans binding to anti-KL
      6/mAb were compared with one another by surface plasmon resonance. Sequentially,
      related radiolabeled oligosaccharides were enzymatically synthesized and analyzed
      for binding to a KL-6/mAb-conjugated affinity column. 3'-sialylated, 6'-sulfated
      LNnT [Neu5Acalpha2-3(SO(3)(-)-6)Galbeta1-4GlcNAcbeta1-3Galbeta1-4Glc], 3'
      sialylated, 6-sulfated core 1 [Neu5Acalpha2-3Galbeta1-3(SO(3)(-)-6)GalNAc] and
      disulfated core 1 SO(3)(-)-3Galbeta1-3(SO(3)(-)-6)GalNAc exhibited substantial
      affinity for KL-6/mAb, and 3'-sulfated core 1 derivatives [SO(3)(-)-3Galbeta1
      3(+/-Neu5Acalpha2-6)GalNAc] and 3'-sialylated core 1 weakly interacted with KL
      6/mAb. These results indicated that the possible carbohydrate epitopes of KL
      6/mAb involve not only 3'-sialylated core 1 but also novel core 1 and extended
      core 1 with sulfate and sialic acid residues. Epitope expressing changes with
      suppression or over-expression of the Gal6ST (Gal 6-O-sulfotransferase) gene,
      suggesting that Gal6ST is involved in the biosynthesis of the unique epitopes of
      KL-6/mAb.

PMID- 21880671
TI  - Angiotensin receptor modulation and cardiovascular remodeling.

PMID- 21880672
TI  - Venous thromboembolism does not share strong familial susceptibility with
      ischemic stroke: a nationwide family study in Sweden.
AB  - BACKGROUND: Coagulation allelic variants associated with venous thromboembolism
      (VTE) have been suggested to be involved in the pathogenesis of ischemic stroke.
      This nationwide study aimed at determining whether VTE shares familial
      susceptibility with ischemic stroke. METHOD AND RESULTS: The Swedish
      Multigeneration Register of 0- to 75-year-old subjects was linked to the Swedish
      Hospital Discharge Register and the Cause of Death Register for the period 1987
      to 2007. Odds ratios (ORs) for VTE and ischemic stroke were determined in 2 ways:
      odds of ischemic stroke in offspring whose parents had been diagnosed with VTE,
      and odds of VTE in offspring whose parents had been diagnosed with ischemic
      stroke. The analyses were repeated for siblings and spouses. Offspring of parents
      with VTE (n=25,929) were at increased risk for ischemic stroke (n=5595): OR, 1.10
      (95% confidence interval [CI], 1.06-1.14). Siblings of probands with VTE
      (n=45,132) had no increased risk of ischemic stroke (n=1716): OR, 1.05 (95% CI,
      1.00-1.11). Spouses of probands with VTE (n=24,106) were at increased risk for
      ischemic stroke (n=940): OR, 1.18 (95% CI, 1.10-1.27). The risks for VTE in
      relatives of probands with ischemic stroke were OR, 1.15; 95% CI, 1.10-1.21
      (offspring); OR, 1.07; 95% CI, 1.02-1.12 (siblings); and OR, 1.21; 95% CI, 1.11
      1.32 (spouses). CONCLUSIONS: VTE does not share strong familial susceptibility
      with ischemic stroke in the Swedish population. Moreover, familial nongenetic
      factors contribute to the observed weak familial associations. The present study
      suggests that it is unlikely that strong shared disease-causing mutations exist
      to a large extent in the Swedish population.

PMID- 21880673
TI  - Protein interaction-based genome-wide analysis of incident coronary heart
      disease.
AB  - BACKGROUND: Network-based approaches may leverage genome-wide association (GWA)
      analysis by testing for the aggregate association across several pathway members.
      We aimed to examine if networks of genes that represent experimentally determined
      protein-protein interactions (PPIs) are enriched in genes associated with risk of
      coronary heart disease (CHD). METHODS AND RESULTS: Genome-wide association
      analyses of approximately ~700,000 single-nucleotide polymorphisms in 899
      incident CHD cases and 1823 age- and sex-matched controls within the Nurses'
      Health and the Health Professionals Follow-up Studies were used to assign
      genewise P values. A large database of PPIs was used to assemble 8351 unbiased
      protein complexes and corresponding gene sets. Superimposed genewise P values
      were used to rank gene sets based on their enrichment in genes associated with
      CHD. After correcting for the number of complexes tested, 1 gene set was
      overrepresented in CHD-associated genes (P=0.002). Centered on the beta1
      adrenergic receptor gene (ADRB1), this complex included 18 protein interaction
      partners that have not been identified as candidate loci for CHD. Of the 19 genes
      in the top complex, 5 are involved in abnormal cardiovascular system
      physiological features based on knockout mice (4-fold enrichment; Fisher exact
      test, P=0.006). Ingenuity pathway analysis revealed that canonical pathways,
      especially related to blood pressure regulation, were significantly enriched in
      the genes from the top complex. CONCLUSIONS: The integration of a GWA study with
      PPI data successfully identifies a set of candidate susceptibility genes for
      incident CHD that would have been missed in single-marker GWA analysis.

PMID- 21880674
TI  - Integration of 3D electroanatomic maps and magnetic resonance scar
      characterization into the navigation system to guide ventricular tachycardia
      ablation.
AB  - BACKGROUND: Scar heterogeneity identified with contrast-enhanced cardiac magnetic
      resonance (CE-CMR) has been related to its arrhythmogenic potential by using
      different algorithms. The purpose of the study was to identify the algorithm that
      best fits with the electroanatomic voltage maps (EAM) to guide ventricular
      tachycardia (VT) ablation. METHODS AND RESULTS: Three-dimensional scar
      reconstructions from preprocedural CE-CMR study at 3T were obtained and compared
      with EAMs of 10 ischemic patients submitted for a VT ablation. Three-dimensional
      scar reconstructions were created for the core (3D-CORE) and border zone (3D-BZ),
      applying cutoff values of 50%, 60%, and 70% of the maximum pixel signal intensity
      to discriminate between core and BZ. The left ventricular cavity from CE-CMR (3D
      LV) was merged with the EAM, and the 3D-CORE and 3D-BZ were compared with the
      corresponding EAM areas defined with standard cutoff voltage values. The best
      match was obtained when a cutoff value of 60% of the maximum pixel signal
      intensity was used, both for core (r(2)=0.827; P<0.001) and BZ (r(2)=0.511;
      P=0.020), identifying 69% of conducting channels (CC) observed in the EAM.
      Matching improved when only the subendocardial half of the wall was segmented
      (CORE: r(2)=0.808; P<0.001 and BZ: r(2)=0.485; P=0.025), identifying 81% of CC.
      When comparing the location of each bipolar voltage intracardiac electrogram with
      respect to the 3D CE-CMR-derived structures, a Cohen kappa coefficient of 0.70
      was obtained. CONCLUSIONS: Scar characterization by means of high resolution CE
      CMR resembles that of EAM and can be integrated into the CARTO system to guide VT
      ablation.

PMID- 21880675
TI  - Assessing epicardial substrate using intracardiac echocardiography during VT
      ablation.
AB  - BACKGROUND: Intracardiac echocardiography (ICE) has played a limited role in
      defining the substrate for ventricular tachycardia (VT). The purpose of this
      study was to assess whether ICE could identify abnormal epicardial substrate in
      patients with nonischemic cardiomyopathy (NICM) and VT. METHODS AND RESULTS: We
      studied 18 patients with NICM and recurrent VT who had abnormal echogenicity
      identified on ICE imaging. Detailed left ventricular (LV) endocardial and
      epicardial electroanatomic mapping was performed in all patients. Low-voltage
      areas (<1.0 mV) in the epicardium were analyzed. ICE imaging in the NICM group
      was compared to a control group of 30 patients with structurally normal hearts
      who underwent ICE imaging for other ablation procedures. In 18 patients (age,
      53+/-13 years; 17 men) with NICM (ejection fraction, 37+/-13%), increased
      echogenicity was identified in the lateral LV by ICE imaging. LV endocardial
      electroanatomic mapping identified normal voltage in 9 patients and at least 1
      confluent low-voltage area (6.6 cm(2); minimum-maximum, 2.1-31.7 cm(2)) in 9
      patients (5 posterolateral LV, 4 perivalvular LV). Detailed epicardial mapping
      revealed areas of low voltage (39 cm(2); minimum-maximum, 18.5-96.3 cm(2)) and
      abnormal, fractionated electrograms in all 18 patients (15 posterolateral LV, 3
      lateral LV). In all patients, the epicardial scar identified by electroanatomic
      mapping correlated with the echogenic area identified on ICE imaging. ICE imaging
      identified no areas of increased echogenicity in the control group. CONCLUSIONS:
      ICE imaging identified increased echogenicity in the lateral wall of the LV that
      correlated to abnormal epicardial substrate. These findings suggest that ICE
      imaging may be useful to identify epicardial substrate in NICM.

PMID- 21880676
TI  - Expression profile of maize (Zea mays L.) embryonic axes during germination:
      translational regulation of ribosomal protein mRNAs.
AB  - Seed germination is a critical developmental period for plant propagation.
      Information regarding gene expression within this important period is relevant
      for understanding the main biochemical processes required for successful
      germination, particularly in maize, one of the most important cereals in the
      world. The present research focuses on the global microarray analysis of
      differential gene expression between quiescent and germinated maize embryo
      stages. This analysis revealed that a large number of mRNAs stored in the
      quiescent embryonic axes (QEAs) were differentially regulated during germination
      in the 24 h germinated embryonic axes (GEAs). These genes belong to 14 different
      functional categories and most of them correspond to metabolic processes,
      followed by transport, transcription and translation. Interestingly, the
      expression of mRNAs encoding ribosomal proteins [(r)-proteins], required for new
      ribosome formation during this fast-growing period, remains mostly unchanged
      throughout the germination process, suggesting that these genes are not regulated
      at the transcriptional level during this developmental period. To investigate
      this issue further, comparative microarray analyses on polysomal mRNAs from
      growth-stimulated and non-stimulated GEAs were performed. The results revealed
      that (r)-protein mRNAs accumulate to high levels in polysomes of the growth
      stimulated tissues, indicating a translational control mechanism to account for
      the rapid (r)-protein synthesis observed within this period. Bioinformatic
      analysis of (r)-protein mRNAs showed that 5' TOP (tract of pyrimidines)-like
      sequences are present only in the 5'-untranslated region set of up-regulated (r)
      protein mRNAs. This overall approach to the germination process allows an in
      depth view of molecular changes, enabling a broader understanding of the
      regulatory mechanisms that occur during this process.

PMID- 21880677
TI  - Media smart.

PMID- 21880678
TI  - Bad medicine: melanoma.

PMID- 21880679
TI  - Confessions of a technophile.

PMID- 21880680
TI  - NIH updates its conflict of interest guidelines.

PMID- 21880681
TI  - Canadian regulators dismiss complaint about campaign publicising low
      testosterone.

PMID- 21880682
TI  - Health secretary will no longer be obliged to provide health service under new
      bill, says legal opinion.

PMID- 21880683
TI  - Gaddafi's forces attacked hospitals, patients, and health professionals, report
      confirms.

PMID- 21880684
TI  - Vaccines rarely cause adverse events, Institute of Medicine finds.

PMID- 21880685
TI  - Bacterium blocks transmission of dengue by mosquitoes.

PMID- 21880686
TI  - Two thirds of trusts in England fail to meet new accident and emergency target.

PMID- 21880687
TI  - Social care homes: what the media forget to tell us.

PMID- 21880688
TI  - Magnetic resonance image of the pelvis.

PMID- 21880689
TI  - Global fall in neonatal deaths over past 20 years is too slow, says study.

PMID- 21880690
TI  - Career intentions of medical students in the setting of Nepal's rapidly expanding
      private medical education system.
AB  - The number of medical students trained in Nepal each year has increased nearly
      fifty-fold in the last 15 years, primarily through the creation of private
      medical schools. It is unknown where this expanding cohort of new physicians will
      ultimately practice. We distributed an anonymous survey to students in their last
      2 years of medical school at four medical schools in Nepal to examine two
      dimensions of career intention: the intention to practice in Nepal and the
      intention to practice in rural areas. Eighty-five per cent of the eligible study
      population participated, for a total of 469 medical students. Of these, 88%
      thought it was likely they would practice in Nepal and 88% thought it likely they
      would practice in urban areas. Those students who indicated a greater likelihood
      of practicing abroad came from families with higher incomes, were more likely to
      think earning a good salary was very important to their decision to become a
      physician, and were less likely to think they could earn a good salary in Nepal.
      Students whose tuition was paid by the government were no more likely to indicate
      an intention to practice in Nepal than students paying their own tuition at
      private medical schools. Students who indicated a greater likelihood of
      practicing in rural areas were more likely to be male, to have gone to a
      government secondary school, to have been born in a village, or to have received
      a scholarship from the Ministry of Education that requires rural service. Based
      on our findings, we suggest the following policy changes: (1) medical schools
      consider selecting for students from rural backgrounds or government secondary
      schools who are more likely to intend to practice in rural areas, and (2)
      increase the number of post-graduate positions--weighted toward rural health
      needs--to retain students in Nepal.

PMID- 21880691
TI  - Introduction to the symposium: responses of organisms to climate change: a
      synthetic approach to the role of thermal adaptation.
AB  - On a global scale, changing climates are affecting ecological systems across
      multiple levels of biological organization. Moreover, climates are changing at
      rates unprecedented in recent geological history. Thus, one of the most pressing
      concerns of the modern era is to understand the biological responses to climate
      such that society can both adapt and implement measures that attempt to offset
      the negative impacts of a rapidly changing climate. One crucial question, to
      understand organismal responses to climate, is whether the ability of organisms
      to adapt can keep pace with quickly changing environments. To address this
      question, a syntheses of knowledge from a broad set of biological disciplines
      will be needed that integrates information from the fields of ecology, behavior,
      physiology, genetics, and evolution. This symposium assembled a diverse group of
      scientists from these subdisciplines to present their perspectives regarding the
      ability of organisms to adapt to changing climates. Specifically, the goals of
      this symposia were to (1) highlight what each discipline brings to a discussion
      of organismal responses to climate, (2) to initiate and foster a discussion to
      break barriers in the transfer of knowledge across disciplines, and (3) to
      synthesize an approach to address ongoing issues concerning biological responses
      to climate.

PMID- 21880692
TI  - The neuroecology of dimethyl sulfide: a global-climate regulator turned marine
      infochemical.
AB  - Information transfer influences food-web dynamics in the marine environment, but
      infochemicals involved in these processes are only beginning to be understood.
      Dimethylsulfoniopropionate (DMSP) is produced by phytoplankton and other marine
      algae, and has been studied primarily in the context of sulfur cycling and
      regulation of global climate. My laboratory has been investigating DMSP and its
      breakdown product, dimethyl sulfide as infochemicals associated with trophic
      interactions in marine habitats, including sub-Antarctic and coral reef
      ecosystems. Using a neuroecological approach, our work has established that these
      biogenic sulfur compounds serve as critical signal molecules in marine systems
      and provides us with a more mechanistic understanding of how climate change may
      impact information transfer within marine food webs.

PMID- 21880693
TI  - Characterization of kinase inhibitors using different phosphorylation states of
      colony stimulating factor-1 receptor tyrosine kinase.
AB  - It is known that some kinase inhibitors are sensitive to the phosphorylation
      state of the kinase, and therefore those compounds can discriminate between a
      phosphorylated and unphosphorylated protein. In this study, we prepared two
      colony stimulating factor-1 receptor (CSF-1R) tyrosine kinase proteins: one
      highly phosphorylated by autophosphorylation and the other dephosphorylated by
      phosphatase treatment. These kinases were subjected to an activity-based assay to
      investigate the effect of their phosphorylation state on the potency of several
      kinase inhibitors. Dasatinib, sorafenib, PD173074 and staurosporine showed
      similar inhibition against different phosphorylation states of CSF-1R, but
      pazopanib, sunitinib, GW2580 and imatinib showed more potent inhibition against
      dephosphorylated CSF-1R. Binding analysis of the inhibitors to the two different
      phosphorylation forms of CSF-1R, using surface plasmon resonance spectrometry,
      revealed that staurosporine bound to both forms with similar affinity, but
      sunitinib bound to the dephosphorylated form with higher affinity. Thus, these
      observations suggest that sunitinib binds preferentially to the inactive form,
      preventing the activation of CSF-1R. Screening against different activation
      states of kinases should be an important approach for prioritizing compounds and
      should facilitate inhibitor design.

PMID- 21880694
TI  - PPARgamma attenuates intimal hyperplasia by inhibiting TLR4-mediated inflammation
      in vascular smooth muscle cells.
AB  - AIMS: Peroxisome proliferator-activated receptor gamma (PPARgamma) has been
      reported to attenuate intimal hyperplasia. This study aimed to test the
      hypothesis that PPARgamma inhibits intimal hyperplasia through suppressing Toll
      like receptor 4 (TLR4)-mediated inflammation in vascular smooth muscle cells.
      METHODS AND RESULTS: TLR4(-/-) mice on a C57BL/6J background were used. Increased
      TLR4 and pro-inflammatory cytokines were observed in wire-injury-induced carotid
      neointima and in platelet-derived growth factor (PDGF)-activated vascular smooth
      muscle cells. The TLR4 deficiency protected the injured carotid from neointimal
      formation and impaired the cellular proliferation and migration in response to
      lipopolysaccharide and PDGF. Rosiglitazone attenuated intimal hyperplasia.
      Overexpression of PPARgamma suppressed PDGF-induced proliferation and migration
      and inhibited TLR4-mediated inflammation in vascular smooth muscle cells, while
      PPARgamma silencing exerted the opposite effect. Lipopolysaccharide counteracted
      the inhibitory effect of PPARgamma on PDGF-induced proliferation and migration.
      Eritoran suppressed the proliferation and migration induced by PDGF and PPARgamma
      silencing. Vascular smooth muscle cells derived from TLR4(-/-) mice showed
      impaired proliferation and migration upon PDGF activation and displayed no
      response to PPARgamma manipulation. CONCLUSION: PPARgamma inhibits vascular
      smooth muscle cell proliferation and migration by suppressing TLR4-mediated
      inflammation and ultimately attenuates intimal hyperplasia after carotid injury.

PMID- 21880695
TI  - Effects of ostracism and social connection-related activities on adolescents'
      motivation to eat and energy intake.
AB  - OBJECTIVE: Assess the effect of ostracism and social connection-related
      activities on adolescents' motivation to eat and their energy intake. METHODS:
      Participants (n = 103; M age = 13.6 years) were either ostracized or included
      when playing a computer game, Cyberball. Next, they wrote about their friend
      (social-connection), watched television (distraction), or completed Sudoku
      puzzles (cognitive-load), and then completed a task to earn points toward snack
      food and/or socializing. Afterwards, participants were given access to food and
      social activities. RESULTS: Ostracized adolescents were more motivated to earn
      food than adolescents who were in the included/control condition. Follow-up
      contrasts indicated that ostracized adolescents who wrote about friends worked
      more for food points and consumed more food than other adolescents. CONCLUSION:
      Results suggest that social connection-related activities following ostracism may
      further deplete self-regulatory resources, thereby resulting in increased
      unhealthy food patterns. Study limitations as well as clinical implications of
      these findings are discussed.

PMID- 21880696
TI  - Normal in the blood, abnormal in the urine.

PMID- 21880697
TI  - Superior vena cava syndrome related fluid collection in retropharyngeal space.

PMID- 21880698
TI  - Risk factors of vitamin K antagonist overcoagulation.
AB  - OBJECTIVES: The aims of this prospective study were to identify, in vitamin K
      antagonist (VKA)-treated patients, factors associated with INR values: (i)
      greater than 6.0. and (ii) ranging from 4.0 to 6.0 complicated with bleeding. We
      also assessed VKA-related morbidity in these patients. METHODS: During a 6-month
      period, 3090 consecutive patients were referred to our Department of Internal
      Medicine, including 412 VKA-treated patients. At admission, the medical records
      of VKA-treated patients were reviewed for type, duration and indication of VKA
      therapy, previous medical history of VKA-related hemorrhage, comorbidities and
      concomitant medications. RESULTS: Forty of the 412 VKA-treated patients (9.7%)
      exhibited oral anticoagulant related overcoagulation. VKA overcoagulation was
      associated with high morbidity, leading to major bleeding in 27.5% of cases;
      moreover, 12.5% of these patients died, death being mainly due to major bleeding.
      Under multivariate analysis, significant factors for VKA-related overcoagulation
      were as follows: previous medical history of VKA therapy-related hemorrhage
      (P=0.00001) and INR levels over therapeutic range (P=0.0006), chronic liver
      disease (P=0.03), therapy with amiodarone (P=0.009); in contrast, statin therapy
      was found to be a protective factor of VKA overcoagulation (P=0.008).
      CONCLUSIONS: The knowledge of predictive factors of VKA-related overcoagulation
      seems of utmost importance to improve patients' management. Our study underlines
      the fact that the potential of drug interaction should be taken into account when
      choosing amiodarone for patients receiving VKAs. Interestingly, long-term (>6
      month) statin therapy may be a protective factor of VKA overcoagulation. Our
      findings, therefore, suggest that there may be no need to switch long-term users
      of VKA and statin to a safer alternative therapy.

PMID- 21880699
TI  - 'Ablation before pacemaker' in a patient with bradycardia: a case report.

PMID- 21880700
TI  - Unusual site of carotid aneurysm.

PMID- 21880701
TI  - Robustness portraits of diverse biological networks conserved despite order-of
      magnitude parameter uncertainty.
AB  - MOTIVATION: Biological networks are robust to a wide variety of internal and
      external perturbations, yet fragile or sensitive to a small minority of
      perturbations. Due to this rare sensitivity of networks to certain perturbations,
      it is unclear how precisely biochemical parameters must be experimentally
      measured in order to accurately predict network function. RESULTS: Here, we
      examined a model of cardiac beta-adrenergic signaling and found that its
      robustness portrait, a global measure of steady-state network function, was well
      conserved even when all parameters were rounded to their nearest 1-2 orders of
      magnitude. In contrast, beta-adrenergic network kinetics were more sensitive to
      parameter precision. This analysis was then extended to 10 additional networks,
      including Escherichia coli chemotaxis, stem cell differentiation and cytokine
      signaling, of which nine exhibited conserved robustness portraits despite the
      order-of-magnitude approximation of their biochemical parameters. Thus, both
      fragile and robust aspects of diverse biological networks are largely shaped by
      network topology and can be predicted despite order-of-magnitude uncertainty in
      biochemical parameters. These findings suggest an iterative strategy where order
      of-magnitude models are used to prioritize experiments toward the fragile network
      elements that require precise measurements, efficiently driving model revision.
      CONTACT: jsaucerman@virginia.edu SUPPLEMENTARY INFORMATION: Supplementary data
      are available at Bioinformatics online.

PMID- 21880702
TI  - PepCrawler: a fast RRT-based algorithm for high-resolution refinement and binding
      affinity estimation of peptide inhibitors.
AB  - MOTIVATION: Design of protein-protein interaction (PPI) inhibitors is a key
      challenge in structural bioinformatics and computer-aided drug design. Peptides,
      which partially mimic the interface area of one of the interacting proteins, are
      natural candidates to form protein-peptide complexes competing with the original
      PPI. The prediction of such complexes is especially challenging due to the high
      flexibility of peptide conformations. RESULTS: In this article, we present
      PepCrawler, a new tool for deriving binding peptides from protein-protein
      complexes and prediction of peptide-protein complexes, by performing high
      resolution docking refinement and estimation of binding affinity. By using a fast
      path planning approach, PepCrawler rapidly generates large amounts of flexible
      peptide conformations, allowing backbone and side chain flexibility. A newly
      introduced binding energy funnel 'steepness score' was applied for the evaluation
      of the protein-peptide complexes binding affinity. PepCrawler simulations
      predicted high binding affinity for native protein-peptide complexes benchmark
      and low affinity for low-energy decoy complexes. In three cases, where wet lab
      data are available, the PepCrawler predictions were consistent with the data.
      Comparing to other state of the art flexible peptide-protein structure prediction
      algorithms, our algorithm is very fast, and takes only minutes to run on a single
      PC. AVAILABILITY: http://bioinfo3d.cs.tau.ac.il/PepCrawler/ CONTACT:
      eladdons@tau.ac.il; wolfson@tau.ac.il.

PMID- 21880703
TI  - AluHunter: a database of potentially polymorphic Alu insertions for use in
      primate phylogeny and population genetics.
AB  - SUMMARY: AluHunter is a database of taxon-specific primate Alu elements for use
      in phylogeny and population genetics. The software automatically isolates
      potentially polymorphic Alu insertions in sequences submitted to GenBank by
      screening the elements against reference genomes. The resultant database of
      variable markers is a valuable resource for researchers interested in
      characterizing Alu elements in their primate taxon of interest. AVAILABILITY AND
      IMPLEMENTATION: The AluHunter database can be accessed at
      http://www.aluhunter.com. CONTACT: cmb433@nyu.edu.

PMID- 21880705
TI  - Adaptor protein-3 (AP-3) complex mediates the biogenesis of acidocalcisomes and
      is essential for growth and virulence of Trypanosoma brucei.
AB  - Acidocalcisomes are acidic calcium and polyphosphate storage organelles found in
      a diverse range of organisms. Here we present evidence that the biogenesis of
      acidocalcisomes in Trypanosoma brucei is linked to the expression of adaptor
      protein-3 (AP-3) complex. Localization studies in cell lines expressing beta3 and
      delta subunits of AP-3 fused to epitope tags revealed their partial co
      localization with the vacuolar proton pyrophosphatase, a marker of
      acidocalcisomes, with the Golgi marker Golgi reassembly and stacking protein, and
      with antibodies against the small GTPase Rab11. Ablation of the beta3 subunit by
      RNA interference (RNAi) resulted in disappearance of acidocalcisomes from both
      procyclic and bloodstream form trypanosomes, as revealed by immmunofluorescence
      and electron microscopy assays, with no alterations in trafficking of different
      markers to lysosomes. Knockdown of the beta3 subunit resulted in lower acidic
      calcium, pyrophosphate, and polyphosphate content as well as defects in growth in
      culture, resistance to osmotic stress, and virulence in mice. Similar results
      were obtained by knocking down the expression of the delta subunit of AP-3. These
      results indicate that AP-3 is essential for the biogenesis of acidocalcisomes and
      for growth and virulence of T. brucei.

PMID- 21880704
TI  - The treatment of differentiated thyroid cancer in children: emphasis on surgical
      approach and radioactive iodine therapy.
AB  - Pediatric thyroid cancer is a rare disease with an excellent prognosis. Compared
      with adults, epithelial-derived differentiated thyroid cancer (DTC), which
      includes papillary and follicular thyroid cancer, presents at more advanced
      stages in children and is associated with higher rates of recurrence. Because of
      its uncommon occurrence, randomized trials have not been applied to test best
      care options in children. Even in adults that have a 10-fold or higher incidence
      of thyroid cancer than children, few prospective trials have been executed to
      compare treatment approaches. We recognize that treatment recommendations have
      changed over the past few decades and will continue to do so. Respecting the
      aggressiveness of pediatric thyroid cancer, high recurrence rates, and the
      problems associated with decades of long-term follow-up, a premium should be
      placed on treatments that minimize risk of recurrence and the adverse effects of
      treatments and facilitate follow-up. We recommend that total thyroidectomy and
      central compartment lymph node dissection is the surgical procedure of choice for
      children with DTC if it can be performed by a high-volume thyroid surgeon. We
      recommend radioactive iodine therapy for remnant ablation or residual disease for
      most children with DTC. We recommend long-term follow-up because disease can
      recur decades after initial diagnosis and therapy. Considering the complexity of
      DTC management and the potential complications associated with therapy, it is
      essential that pediatric DTC be managed by physicians with expertise in this
      area.

PMID- 21880707
TI  - Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D beta
      lactamase from Acinetobacter baumannii.
AB  - Carbapenem-hydrolyzing class D beta-lactamases (CHDLs) represent an emerging
      antibiotic resistance mechanism encountered among the most opportunistic Gram
      negative bacterial pathogens. We report here the substrate kinetics and
      mechanistic characterization of a prominent CHDL, the OXA-58 enzyme, from
      Acinetobacter baumannii. OXA-58 uses a carbamylated lysine to activate the
      nucleophilic serine used for beta-lactam hydrolysis. The deacylating water
      molecule approaches the acyl-enzyme species, anchored at this serine (Ser-83),
      from the alpha-face. Our data show that OXA-58 retains the catalytic machinery
      found in class D beta-lactamases, of which OXA-10 is representative. Comparison
      of the homology model of OXA-58 and the recently solved crystal structures of OXA
      24 and OXA-48 with the OXA-10 crystal structure suggests that these CHDLs have
      evolved the ability to hydrolyze imipenem, an important carbapenem in clinical
      use, by subtle structural changes in the active site. These changes may
      contribute to tighter binding of imipenem to the active site and removal of
      steric hindrances from the path of the deacylating water molecule.

PMID- 21880706
TI  - Chemical genetics of zipper-interacting protein kinase reveal myosin light chain
      as a bona fide substrate in permeabilized arterial smooth muscle.
AB  - Zipper-interacting protein kinase (ZIPK) has been implicated in Ca(2+)
      independent smooth muscle contraction, although its specific role is unknown. The
      addition of ZIPK to demembranated rat caudal arterial strips induced an increase
      in force, which correlated with increases in LC(20) and MYPT1 phosphorylation.
      However, because of the number of kinases capable of phosphorylating LC(20) and
      MYPT1, it has proven difficult to identify the mechanism underlying ZIPK action.
      Therefore, we set out to identify bona fide ZIPK substrates using a chemical
      genetics method that takes advantage of ATP analogs with bulky substituents at
      the N(6) position and an engineered ZIPK capable of utilizing such substrates.
      (32)P-Labeled 6-phenyl-ATP and ZIPK-L93G mutant protein were added to
      permeabilized rat caudal arterial strips, and substrate proteins were detected by
      autoradiography following SDS-PAGE. Mass spectrometry identified LC(20) as a
      direct target of ZIPK in situ for the first time. Tissues were also exposed to 6
      phenyl-ATP and ZIPK-L93G in the absence of endogenous ATP, and putative ZIPK
      substrates were identified by Western blotting. LC(20) was thereby confirmed as a
      direct target of ZIPK; however, no phosphorylation of MYPT1 was detected. We
      conclude that ZIPK is involved in the regulation of smooth muscle contraction
      through direct phosphorylation of LC(20).

PMID- 21880709
TI  - DeltaNp63alpha protein triggers epithelial-mesenchymal transition and confers
      stem cell properties in normal human keratinocytes.
AB  - p63 is a p53 family protein required for morphogenesis and postnatal regeneration
      of epithelial tissues. Here we demonstrate that DeltaNp63alpha, a p63 isoform
      lacking the N-terminal transactivation domain, induces epithelial-mesenchymal
      transition (EMT) in primary human keratinocytes in a TGF-beta-dependent manner.
      Rapidly proliferating normal human epidermal keratinocytes (NHEK) were infected
      with retroviral vector expressing DeltaNp63alpha or empty vector and serially
      subcultured until replicative senescence. No phenotypic changes were observed
      until the culture reached senescence. Then the DeltaNp63alpha-transduced cells
      underwent morphological changes resembling mesenchymal cells and acquired the EMT
      phenotype. Treatment with exogenous TGF-beta accelerated EMT in presenescent
      DeltaNp63alpha-transduced cells, whereas the inhibition of TGF-beta signaling
      reversed the EMT phenotype. TGF-beta treatment alone led to growth arrest in
      control NHEK with no evidence of EMT, indicating that DeltaNp63alpha altered the
      cellular response to TGF-beta treatment. DeltaNp63alpha-transduced cells
      acquiring EMT gained the ability to be differentiated to osteo-/odontogenic and
      adipogenic pathways, resembling mesenchymal stem cells. Furthermore, these cells
      expressed enhanced levels of Nanog and Lin28, which are transcription factors
      associated with pluripotency. These data indicate that EMT required
      DeltaNp63alpha transduction and intact TGF-beta signaling in NHEK.

PMID- 21880708
TI  - Non-equivalent role of inter- and intramolecular hydrogen bonds in the insulin
      dimer interface.
AB  - Apart from its role in insulin receptor (IR) activation, the C terminus of the B
      chain of insulin is also responsible for the formation of insulin dimers. The
      dimerization of insulin plays an important role in the endogenous delivery of the
      hormone and in the administration of insulin to patients. Here, we investigated
      insulin analogues with selective N-methylations of peptide bond amides at
      positions B24, B25, or B26 to delineate their structural and functional
      contribution to the dimer interface. All N-methylated analogues showed impaired
      binding affinities to IR, which suggests a direct IR-interacting role for the
      respective amide hydrogens. The dimerization capabilities of analogues were
      investigated by isothermal microcalorimetry. Selective N-methylations of B24,
      B25, or B26 amides resulted in reduced dimerization abilities compared with
      native insulin (K(d) = 8.8 MUM). Interestingly, although the N-methylation in
      [NMeTyrB26]-insulin or [NMePheB24]-insulin resulted in K(d) values of 142 and 587
      MUM, respectively, the [NMePheB25]-insulin did not form dimers even at high
      concentrations. This effect may be attributed to the loss of intramolecular
      hydrogen bonding between NHB25 and COA19, which connects the B-chain beta-strand
      to the core of the molecule. The release of the B-chain beta-strand from this
      hydrogen bond lock may result in its higher mobility, thereby shifting solution
      equilibrium toward the monomeric state of the hormone. The study was complemented
      by analyses of two novel analogue crystal structures. All examined analogues
      crystallized only in the most stable R(6) form of insulin oligomers (even if the
      dimer interface was totally disrupted), confirming the role of R(6)-specific
      intra/intermolecular interactions for hexamer stability.

PMID- 21880710
TI  - Phosphorylation of right open reading frame 2 (Rio2) protein kinase by polo-like
      kinase 1 regulates mitotic progression.
AB  - Polo-like kinase 1 (Plk1) plays essential roles during multiple stages of mitosis
      by phosphorylating a number of substrates. Here, we report that the atypical
      protein kinase Rio2 is a novel substrate of Plk1 and can be phosphorylated by
      Plk1 at Ser-335, Ser-380, and Ser-548. Overexpression of Rio2 causes a prolonged
      mitotic exit whereas knockdown of Rio2 accelerates mitotic progression,
      suggesting that Rio2 is required for the proper mitotic progression.
      Overexpression of phospho-mimicking mutant Rio2 S3D but not the
      nonphosphorylatable mutant Rio2 S3A displays a profile similar to that of wild
      type Rio2. These results indicate that the phosphorylation status of Rio2
      correlates with its function in mitosis. Furthermore, time-lapse imaging data
      show that overexpression of Rio2 but not Rio2 S3A results in a slowed metaphase
      anaphase transition. Collectively, these findings strongly indicate that the Plk1
      mediated phosphorylation of Rio2 regulates metaphase-anaphase transition during
      mitotic progression.

PMID- 21880711
TI  - Crystal structure of NALP3 protein pyrin domain (PYD) and its implications in
      inflammasome assembly.
AB  - NALP3 inflammasome, composed of the three proteins NALP3, ASC, and Caspase-1, is
      a macromolecular complex responsible for the innate immune response against
      infection with bacterial and viral pathogens. Formation of the inflammasome can
      lead to the activation of inflammatory caspases, such as Caspase-1, which then
      activate pro-inflammatory cytokines by proteolytic cleavage. The assembly of the
      NALP3 inflammasome depends on the protein-interacting domain known as the death
      domain superfamily. NALP3 inflammasome is assembled via a pyrin domain (PYD)/PYD
      interaction between ASC and NALP3 and a caspase recruitment domain/caspase
      recruitment domain interaction between ASC and Caspase-1. As a first step toward
      elucidating the molecular mechanisms of inflammatory caspase activation by
      formation of inflammasome, we report the crystal structure of the PYD from NALP3
      at 1.7-A resolution. Although NALP3 PYD has the canonical six-helical bundle
      structural fold similar to other PYDs, the high resolution structure reveals the
      possible biologically important homodimeric interface and the dynamic properties
      of the fold. Comparison with other PYD structures shows both similarities and
      differences that may be functionally relevant. Structural and sequence analyses
      further implicate conserved surface residues in NALP3 PYD for ASC interaction and
      inflammasome assembly. The most interesting aspect of the structure was the
      unexpected disulfide bond between Cys-8 and Cys-108, which might be important for
      regulation of the activity of NALP3 by redox potential.

PMID- 21880712
TI  - Tumor suppressor and aging biomarker p16(INK4a) induces cellular senescence
      without the associated inflammatory secretory phenotype.
AB  - Cellular senescence suppresses cancer by preventing the proliferation of cells
      that experience potentially oncogenic stimuli. Senescent cells often express
      p16(INK4a), a cyclin-dependent kinase inhibitor, tumor suppressor, and biomarker
      of aging, which renders the senescence growth arrest irreversible. Senescent
      cells also acquire a complex phenotype that includes the secretion of many
      cytokines, growth factors, and proteases, termed a senescence-associated
      secretory phenotype (SASP). The SASP is proposed to underlie age-related
      pathologies, including, ironically, late life cancer. Here, we show that ectopic
      expression of p16(INK4a) and another cyclin-dependent kinase inhibitor,
      p21(CIP1/WAF1), induces senescence without a SASP, even though they induced other
      features of senescence, including a stable growth arrest. Additionally, human
      fibroblasts induced to senesce by ionizing radiation or oncogenic RAS developed a
      SASP regardless of whether they expressed p16(INK4a). Cells induced to senesce by
      ectopic p16(INK4a) expression lacked paracrine activity on epithelial cells,
      consistent with the absence of a functional SASP. Nonetheless, expression of
      p16(INK4a) by cells undergoing replicative senescence limited the accumulation of
      DNA damage and premature cytokine secretion, suggesting an indirect role for
      p16(INK4a) in suppressing the SASP. These findings suggest that p16(INK4a)
      positive cells may not always harbor a SASP in vivo and, furthermore, that the
      SASP is not a consequence of p16(INK4a) activation or senescence per se, but
      rather is a damage response that is separable from the growth arrest.

PMID- 21880713
TI  - Dual targets for mouse mast cell protease-4 in mediating tissue damage in
      experimental bullous pemphigoid.
AB  - Mouse mast cell protease-4 (mMCP-4) has been linked to autoimmune and
      inflammatory diseases, although the exact mechanisms underlying its role in these
      pathological conditions remain unclear. Here, we have found that mMCP-4 is
      critical in a mouse model of the autoimmune skin blistering disease bullous
      pemphigoid (BP). Mice lacking mMCP-4 were resistant to experimental BP.
      Complement activation, mast cell (MC) degranulation, and the early phase of
      neutrophil (PMN) recruitment occurred comparably in mMCP-4(-/-) and WT mice.
      However, without mMCP-4, activation of matrix metalloproteinase (MMP)-9 was
      impaired in cultured mMCP-4(-/-) MCs and in the skin of pathogenic IgG-injected
      mMCP-4(-/-) mice. MMP-9 activation was not fully restored by local reconstitution
      with WT or mMCP-4(-/-) PMNs. Local reconstitution with mMCP-4(+/+) MCs, but not
      with mMCP-4(-/-) MCs, restored blistering, MMP-9 activation, and PMN recruitment
      in mMCP-4(-/-) mice. mMCP-4 also degraded the hemidesmosomal transmembrane
      protein BP180 both in the skin and in vitro. These results demonstrate that mMCP
      4 plays two different roles in the pathogenesis of experimental BP, by both
      activating MMP-9 and by cleaving BP180, leading to injury of the hemidesmosomes
      and extracellular matrix of the basement membrane zone.

PMID- 21880714
TI  - Ligand-receptor interaction between triterpenoids and the 11beta-hydroxysteroid
      dehydrogenase type 2 (11betaHSD2) enzyme predicts their toxic effects against
      tumorigenic r/m HM-SFME-1 cells.
AB  - The present study deals with in silico prediction and in vitro evaluation of the
      selective cytotoxic effects of triterpenoids on tumorigenic human c-Ha-ras and
      mouse c-myc cotransfected highly metastatic serum-free mouse embryo-1 (r/m HM
      SFME-1) cells. Ligand fitting of five different triterpenoids to 11beta
      hydroxysteroid dehydrogenase type 2 (11betaHSD2) was analyzed with a molecular
      modeling method, and glycyrrhetinic acid (GA) was the best-fitted triterpenoid to
      the ligand binding site in 11betaHSD2. Analysis of antiproliferative effects
      revealed that GA, oleanolic acid, and ursolic acid had selective toxicity against
      the tumor cells and that GA was the most potent triterpenoid in its selectivity.
      The toxic activity of the tested triterpenoids against the tumor cells showed
      good correlations with the partition coefficient (logP) and polar surface area
      values. Time-lapse microscopy, fluorescence staining, and confocal laser scanning
      microscopic observation revealed that GA induced morphologic changes typical of
      apoptosis such as cell shrinkage and blebbing and also disrupted the cytoskeletal
      proteins. Furthermore, GA exhibited a strong inhibitory effect on 11betaHSD2
      activity in the tumor cells. Our current results suggest that analysis of the
      ligand-receptor interaction between triterpenoids and 11betaHSD2 can be utilized
      to predict their antitumor effects and that GA can be used as a possible
      chemopreventive and therapeutic antitumor agent. To the best of our knowledge,
      this is the first report on in silico prediction of the toxic effects of
      triterpenoids on tumor cells by 11betaHSD2 inhibition.

PMID- 21880715
TI  - Structure of human SMYD2 protein reveals the basis of p53 tumor suppressor
      methylation.
AB  - SMYD2 belongs to a subfamily of histone lysine methyltransferase and was recently
      identified to methylate tumor suppressor p53 and Rb. Here we report that SMYD2
      prefers to methylate p53 Lys-370 over histone substrates in vitro. Consistently,
      the level of endogenous p53 Lys-370 monomethylation is significantly elevated
      when SMYD2 is overexpressed in vivo. We have solved the high resolution crystal
      structures of the full-length SMYD2 protein in binary complex with its cofactor S
      adenosylmethionine and in ternary complex with cofactor product S
      adenosylhomocysteine and p53 substrate peptide (residues 368-375), respectively.
      p53 peptide binds to a deep pocket of the interface between catalytic SET(1-282)
      and C-terminal domain (CTD) with an unprecedented U-shaped conformation. Subtle
      conformational change exists around the p53 binding site between the binary and
      ternary structures, in particular the tetratricopeptide repeat motif of the CTD.
      In addition, a unique EDEE motif between the loop of anti-parallel beta7 and
      beta8 sheets of the SET core not only interacts with p53 substrate but also forms
      a hydrogen bond network with residues from CTD. These observations suggest that
      the tetratricopeptide repeat and EDEE motif may play an important role in
      determining p53 substrate binding specificity. This is further verified by the
      findings that deletion of the CTD domain drastically reduces the methylation
      activity of SMYD2 to p53 protein. Meanwhile, mutation of EDEE residues impairs
      both the binding and the enzymatic activity of SMYD2 to p53 Lys-370. These data
      together reveal the molecular basis of SMYD2 in specifically recognizing and
      regulating functions of p53 tumor suppressor through Lys-370 monomethylation.

PMID- 21880716
TI  - Synergistic induction of galectin-1 by CCAAT/enhancer binding protein alpha and
      hypoxia-inducible factor 1alpha and its role in differentiation of acute myeloid
      leukemic cells.
AB  - Galectin-1 is a member of the galectin family and has a high affinity for
      galactose and N-acetylglucosamine moieties of glycoproteins. It mediates multiple
      signal transduction pathways to modulate cellular proliferation, survival,
      differentiation, and migration. However, the mechanisms for the regulation of its
      expression remain greatly elusive. We reported previously that galectin-1 is a
      direct target of the hypoxia-inducible factor 1 (HIF-1), a key heterodimeric
      transcriptional factor for the cellular response to hypoxia. Here we show that
      CCAAT/enhancer binding protein alpha (C/EBPalpha), a critical transcriptional
      factor for hematopoietic cell differentiation, can directly activate galectin-1
      through binding to the -48 to -42 bp region of its promoter. Based on the
      physical interaction of C/EBPalpha and HIF-1alpha, the synergistic
      transcriptional activity of C/EBPalpha and HIF-1alpha on the promoter of the
      galectin-1 gene is also found by chromatin immunoprecipitation (ChIP), ChIP
      followed by ChIP (ChIP-reChIP), and luciferase assay. Moreover, knockdown or
      chemical inhibition of galectin-1 partially blocks the differentiation induced by
      HIF-1alpha or C/EBPalpha, which can be rescued by recombinant galectin-1. These
      discoveries would shed new insights on the mechanisms for galectin-1 expression
      regulation and HIF-1alpha- and C/EBPalpha-induced leukemic cell differentiation.

PMID- 21880717
TI  - Identification of novel Ssl0352 protein (NdhS), essential for efficient operation
      of cyclic electron transport around photosystem I, in NADPH:plastoquinone
      oxidoreductase (NDH-1) complexes of Synechocystis sp. PCC 6803.
AB  - Cyanobacterial NADPH:plastoquinone oxidoreductase, or type I NAD(P)H
      dehydrogenase, or the NDH-1 complex is involved in plastoquinone reduction and
      cyclic electron transfer (CET) around photosystem I. CET, in turn, produces extra
      ATP for cell metabolism particularly under stressful conditions. Despite
      significant achievements in the study of cyanobacterial NDH-1 complexes during
      the past few years, the entire subunit composition still remains elusive. To
      identify missing subunits, we screened a transposon-tagged library of
      Synechocystis 6803 cells grown under high light. Two NDH-1-mediated CET (NDH-CET)
      defective mutants were tagged in the same ssl0352 gene encoding a short unknown
      protein. To clarify the function of Ssl0352, the ssl0352 deletion mutant and
      another mutant with Ssl0352 fused to yellow fluorescent protein (YFP) and the
      His(6) tag were constructed. Immunoblotting, mass spectrometry, and confocal
      microscopy analyses revealed that the Ssl0352 protein resides in the thylakoid
      membrane and associates with the NDH-1L and NDH-1M complexes. We conclude that
      Ssl0352 is a novel subunit of cyanobacterial NDH-1 complexes and designate it
      NdhS. Deletion of the ssl0352 gene considerably impaired the NDH-CET activity and
      also retarded cell growth under high light conditions, indicating that NdhS is
      essential for efficient operation of NDH-CET. However, the assembly of the NDH-1L
      and NDH-1M complexes and their content in the cells were not affected in the
      mutant. NdhS contains a Src homology 3-like domain and might be involved in
      interaction of the NDH-1 complex with an electron donor.

PMID- 21880718
TI  - Biochemical studies and ligand-bound structures of biphenyl dehydrogenase from
      Pandoraea pnomenusa strain B-356 reveal a basis for broad specificity of the
      enzyme.
AB  - Biphenyl dehydrogenase, a member of short-chain dehydrogenase/reductase enzymes,
      catalyzes the second step of the biphenyl/polychlorinated biphenyls catabolic
      pathway in bacteria. To understand the molecular basis for the broad substrate
      specificity of Pandoraea pnomenusa strain B-356 biphenyl dehydrogenase (BphB(B
      356)), the crystal structures of the apo-enzyme, the binary complex with NAD(+),
      and the ternary complexes with NAD(+)-2,3-dihydroxybiphenyl and NAD(+)-4,4'
      dihydroxybiphenyl were determined at 2.2-, 2.5-, 2.4-, and 2.1-A resolutions,
      respectively. A crystal structure representing an intermediate state of the
      enzyme was also obtained in which the substrate binding loop was ordered as
      compared with the apo and binary forms but it was displaced significantly with
      respect to the ternary structures. These five structures reveal that the
      substrate binding loop is highly mobile and that its conformation changes during
      ligand binding, starting from a disorganized loop in the apo state to a well
      organized loop structure in the ligand-bound form. Conformational changes are
      induced during ligand binding; forming a well defined cavity to accommodate a
      wide variety of substrates. This explains the biochemical data that shows BphB(B
      356) converts the dihydrodiol metabolites of 3,3'-dichlorobiphenyl, 2,4,4'
      trichlorobiphenyl, and 2,6-dichlorobiphenyl to their respective dihydroxy
      metabolites. For the first time, a combination of structural, biochemical, and
      molecular docking studies of BphB(B-356) elucidate the unique ability of the
      enzyme to transform the cis-dihydrodiols of double meta-, para-, and ortho
      substituted chlorobiphenyls.

PMID- 21880719
TI  - Human C-type lectin domain family 4, member C (CLEC4C/BDCA-2/CD303) is a receptor
      for asialo-galactosyl-oligosaccharides.
AB  - Plasmacytoid dendritic cells are specialized in the production of type I
      interferon (type I IFN), which promotes antiviral and antitumor responses, as
      well as autoimmune disorders. Activation of type I IFN secretion depends on the
      pattern recognition receptors TLR7 and TLR9, which sense microbial RNA and DNA,
      respectively. Type I IFN production is modulated by several receptors, including
      the type II C-type lectin domain family 4, member C (CLEC4C). The natural ligand
      of CLEC4C is unknown. To identify it, here we probed a glycan array with a
      soluble form of the CLEC4C ectodomain. We found that CLEC4C recognizes complex
      type sugars with terminal galactose. Importantly, soluble CLEC4C bound peripheral
      blood leukocytes and tumor cells that express glycans with galactose residues at
      the non-reducing ends. The positive and negative modulation of galactose residues
      on cell membranes was paralleled by the regulation of type I IFN secretion by
      plasmacytoid dendritic cells in co-culture experiments in vitro. These results
      suggest that the modulation in the expression of non-sialylated oligosaccharides
      by invading pathogens or transformed cells may affect type I IFN response and
      immune surveillance.

PMID- 21880720
TI  - 2-thioxanthines are mechanism-based inactivators of myeloperoxidase that block
      oxidative stress during inflammation.
AB  - Myeloperoxidase (MPO) is a prime candidate for promoting oxidative stress during
      inflammation. This abundant enzyme of neutrophils uses hydrogen peroxide to
      oxidize chloride to highly reactive and toxic chlorine bleach. We have identified
      2-thioxanthines as potent mechanism-based inactivators of MPO. Mass spectrometry
      and x-ray crystal structures revealed that these inhibitors become covalently
      attached to the heme prosthetic groups of the enzyme. We propose a mechanism
      whereby 2-thioxanthines are oxidized, and their incipient free radicals react
      with the heme groups of the enzyme before they can exit the active site. 2
      Thioxanthines inhibited MPO in plasma and decreased protein chlorination in a
      mouse model of peritonitis. They slowed but did not prevent neutrophils from
      killing bacteria and were poor inhibitors of thyroid peroxidase. Our study shows
      that MPO is susceptible to the free radicals it generates, and this Achilles'
      heel of the enzyme can be exploited to block oxidative stress during
      inflammation.

PMID- 21880721
TI  - Analysis of two major intracellular phospholipases A(2) (PLA(2)) in mast cells
      reveals crucial contribution of cytosolic PLA(2)alpha, not Ca(2+)-independent
      PLA(2)beta, to lipid mobilization in proximal mast cells and distal fibroblasts.
AB  - Mast cells release a variety of mediators, including arachidonic acid (AA)
      metabolites, to regulate allergy, inflammation, and host defense, and their
      differentiation and maturation within extravascular microenvironments depend on
      the stromal cytokine stem cell factor. Mouse mast cells express two major
      intracellular phospholipases A(2) (PLA(2)s), namely group IVA cytosolic PLA(2)
      (cPLA(2)alpha) and group VIA Ca(2+)-independent PLA(2) (iPLA(2)beta), and the
      role of cPLA(2)alpha in eicosanoid synthesis by mast cells has been well
      documented. Lipidomic analyses of mouse bone marrow-derived mast cells (BMMCs)
      lacking cPLA(2)alpha (Pla2g4a(-/-)) or iPLA(2)beta (Pla2g6(-/-)) revealed that
      phospholipids with AA were selectively hydrolyzed by cPLA(2)alpha, not by
      iPLA(2)beta, during FcepsilonRI-mediated activation and even during fibroblast
      dependent maturation. Neither FcepsilonRI-dependent effector functions nor
      maturation-driven phospholipid remodeling was impaired in Pla2g6(-/-) BMMCs.
      Although BMMCs did not produce prostaglandin E(2) (PGE(2)), the AA released by
      cPLA(2)alpha from BMMCs during maturation was converted to PGE(2) by microsomal
      PGE synthase-1 (mPGES-1) in cocultured fibroblasts, and accordingly, Pla2g4a(-/-)
      BMMCs promoted microenvironmental PGE(2) synthesis less efficiently than wild
      type BMMCs both in vitro and in vivo. Mice deficient in mPGES-1 (Ptges(-/-)) had
      an augmented local anaphylactic response. These results suggest that cPLA(2)alpha
      in mast cells is functionally coupled, through the AA transfer mechanism, with
      stromal mPGES-1 to provide anti-anaphylactic PGE(2). Although iPLA(2)beta is
      partially responsible for PGE(2) production by macrophages and dendritic cells,
      it is dispensable for mast cell maturation and function.

PMID- 21880722
TI  - Glycodelin-A protein interacts with Siglec-6 protein to suppress trophoblast
      invasiveness by down-regulating extracellular signal-regulated kinase (ERK)/c-Jun
      signaling pathway.
AB  - During placentation, the cytotrophoblast differentiates into the villous
      cytotrophoblast and the extravillous cytotrophoblast. The latter invades the
      decidualized endometrium. Glycodelin-A (GdA) is abundantly synthesized by the
      decidua but not the trophoblast. Previous data indicate that GdA suppresses the
      invasion of trophoblast cell lines by down-regulating proteinase expression and
      activities. This study addresses the signaling pathway involved in the above
      phenomenon. GdA was found to suppress phosphorylation of ERKs and expression of
      their downstream effector c-Jun, a component of the transcription factor
      activator protein-1 (AP-1). The involvement of ERKs and c-Jun in suppressing
      trophoblast invasion and biosynthesis of proteinases was confirmed by using siRNA
      knockdown and pharmacological inhibitors. Desialylation reduced binding affinity
      of GdA toward and invasion suppressive activities on the trophoblast. Co
      immunoprecipitation showed that Siglec-6 on the trophoblast was the binding
      protein of GdA. The binding of GdA to Siglec-6 was sialic acid-dependent.
      Treatment with anti-Siglec-6 antibody abolished the invasion suppressive
      activities of GdA. These results show that GdA interacts with Siglec-6 to
      suppress trophoblast invasiveness by down-regulating the ERK/c-Jun signaling
      pathway.

PMID- 21880724
TI  - Atomic resolution x-ray structure of the substrate recognition domain of higher
      plant ribulose-bisphosphate carboxylase/oxygenase (Rubisco) activase.
AB  - The rapid release of tight-binding inhibitors from dead-end ribulose-bisphosphate
      carboxylase/oxygenase (Rubisco) complexes requires the activity of Rubisco
      activase, an AAA+ ATPase that utilizes chemo-mechanical energy to catalyze the
      reactivation of Rubisco. Activase is thought to play a central role in
      coordinating the rate of CO(2) fixation with the light reactions of
      photosynthesis. Here, we present a 1.9 A crystal structure of the C-domain core
      of creosote activase. The fold consists of a canonical four-helix bundle, from
      which a paddle-like extension protrudes that entails a nine-turn helix lined by
      an irregularly structured peptide strand. The residues Lys-313 and Val-316
      involved in the species-specific recognition of Rubisco are located near the tip
      of the paddle. An ionic bond between Lys-313 and Glu-309 appears to stabilize the
      glycine-rich end of the helix. Structural superpositions onto the distant homolog
      FtsH imply that the paddles extend away from the hexameric toroid in a fan-like
      fashion, such that the hydrophobic sides of each blade bearing Trp-302 are facing
      inward and the polar sides bearing Lys-313 and Val-316 are facing outward.
      Therefore, we speculate that upon binding, the activase paddles embrace the
      Rubisco cylinder by placing their hydrophobic patches near the partner protein.
      This model suggests that conformational adjustments at the remote end of the
      paddle may relate to selectivity in recognition, rather than specific ionic
      contacts involving Lys-313. Additionally, the superpositions predict that the
      catalytically critical Arg-293 does not interact with the bound nucleotide.
      Hypothetical ring-ring stacking and peptide threading models for Rubisco
      reactivation are briefly discussed.

PMID- 21880723
TI  - Retinoblastoma protein modulates the inverse relationship between cellular
      proliferation and elastogenesis.
AB  - The mechanism that leads to the inverse relationship between heightened cellular
      proliferation and the cessation of elastic fibers production, observed during
      formation of the arterial occlusions and dermal scars, is not fully understood.
      Because the retinoblastoma protein (Rb), responsible for cell cycle initiation,
      has also been implicated in insulin-like growth factor-I-mediated signaling
      stimulating elastin gene activation, we explored whether differential
      phosphorylation of Rb by various cyclin.cyclin-dependent kinase complexes would
      be responsible for promoting either elastogenic or pro-proliferative signals. We
      first tested cultures of dermal fibroblasts derived from Costello syndrome
      patients, in which heightened proliferation driven by mutated oncogenic H-Ras
      coincides with inhibition of elastogenesis. We found that Costello syndrome
      fibroblasts display elevated level of Rb phosphorylation on serine 780 (Ser(P)
      780-Rb) and that pharmacological inhibition of Ras with radicicol, Mek/Erk with
      PD98059, or cyclin-dependent kinase 4 with PD0332991 not only leads to down
      regulation of Ser(P)-780-Rb levels but also enhances Rb phosphorylation on
      threonine-821 (Thr(P)-821-Rb), which coincides with the recovery of elastin
      production. Then we demonstrated that treatment of normal skin fibroblasts with
      the pro-proliferative PDGF BB also up-regulates Ser(P)-780-Rb levels, but
      treatment with the pro-elastogenic insulin-like growth factor-I activates cyclinE
      cdk2 complex to phosphorylate Rb on Thr-821. Importantly, we have established
      that elevation of Thr(P)-821-Rb promotes Rb binding to the Sp1 transcription
      factor and that successive binding of the Rb-Sp1 complex to the retinoblastoma
      control element within the elastin gene promoter stimulates tropoelastin
      transcription. In summary, we provide novel insight into the role of Rb in
      mediating the inverse relationship between elastogenesis and cellular
      proliferation.

PMID- 21880725
TI  - Stereocontrol of arachidonic acid oxygenation by vertebrate lipoxygenases: newly
      cloned zebrafish lipoxygenase 1 does not follow the Ala-versus-Gly concept.
AB  - Animal lipoxygenases (LOXs) are classified according to their specificity of
      arachidonic acid oxygenation, and previous sequence alignments suggested that S
      LOXs contain a conserved Ala at a critical position at the active site but R-LOXs
      carry a Gly instead. Here we cloned, expressed, and characterized a novel LOX
      isoform from the model vertebrate Danio rerio (zebrafish) that carries a Gly at
      this critical position, classifying this enzyme as putative arachidonic acid R
      LOX. Surprisingly, the almost exclusive arachidonic acid oxygenation product was
      12S-H(p)ETE (hydro(pero)xyeicosatetraenoic acid), and extensive mutation around
      Gly-410 failed to induce R-lipoxygenation. This finding prompted us to explore
      the importance of the corresponding amino acids in other vertebrate S-LOXs. We
      found that Ala-to-Gly exchange in human 15-LOX2 and human platelet 12-LOX induced
      major alterations in the reaction specificity with an increase of specific R
      oxygenation products. For mouse 5-LOX and 12/15-LOX from rabbits, men, rhesus
      monkeys, orangutans, and mice, only minor alterations in the reaction specificity
      were observed. For these enzymes, S-HETE (hydroxyeicosatetraenoic acid) isomers
      remained the major oxygenation products, whereas chiral R-HETEs contributed only
      10-30% to the total product mixture. Taken together these data indicate that the
      Ala-versus-Gly concept may not always predict the reaction specificity of
      vertebrate LOX isoforms.

PMID- 21880726
TI  - Interaction of nectin-like molecule 2 with integrin alpha6beta4 and inhibition of
      disassembly of integrin alpha6beta4 from hemidesmosomes.
AB  - In normal epithelial cells, integrin alpha(6)beta(4) is abundantly expressed and
      forms hemidesmosomes, which is a cellular structure that mediates cell
      extracellular matrix binding. In many types of cancer cells, integrin
      alpha(6)beta(4) is up-regulated, laminin is cleaved, and hemidesmosomes are
      disrupted, eventually causing an enhancement of cancer cell movement and
      facilitation of their invasion. We previously showed that the immunoglobulin-like
      cell adhesion molecule Necl-2 (Nectin-like molecule 2), known as a tumor
      suppressor, inhibits cancer cell movement by suppressing the ErbB3/ErbB2
      signaling. We show here that Necl-2 interacts in cis with integrin
      alpha(6)beta(4). The binding of Necl-2 with integrin beta(4) was mediated by its
      extracellular region. In human colorectal adenocarcinoma Caco-2 cells, integrin
      alpha(6)beta(4) was localized at hemidesmosomes. Small interfering RNA-mediated
      suppression of Necl-2 expression enhanced the phorbol ester-induced disruption of
      the integrin alpha(6)beta(4) complex at hemidesmosomes, whereas expression of
      Necl-2 suppressed the disruption of this structure. These results indicate that
      tumor-suppressive functions of Necl-2 are mediated by the stabilization of the
      hemidesmosome structure in addition to the inhibition of the ErbB3/ErbB2
      signaling.

PMID- 21880727
TI  - Strain-dependent up-regulation of ephrin-B2 protein in periodontal ligament
      fibroblasts contributes to osteogenesis during tooth movement.
AB  - During orthodontic tooth movement, the application of adequate orthodontic forces
      allows teeth to be moved through the alveolar bone. These forces are transmitted
      through the periodontal ligaments (PDL) to the supporting alveolar bone and lead
      to deposition or resorption of bone, depending on whether the tissues are exposed
      to a tensile or compressive mechanical strain. Fibroblasts within the PDL (PDLF)
      are considered to be mechanoresponsive. The transduction mechanisms from
      mechanical loading of the PDLF to the initiation of bone remodeling are not
      clearly understood. Recently, members of the ephrin/Eph family have been shown to
      be involved in the regulation of bone homeostasis. For the first time, we
      demonstrate that PDLF exposed to tensile strain induce the expression of ephrin
      B2 via a FAK-, Ras-, ERK1/2-, and SP1-dependent pathway. Osteoblasts of the
      alveolar bone stimulated with ephrin-B2 increased their osteoblastogenic gene
      expression and showed functional signs of osteoblastic differentiation. In a
      physiological setting, ephrin-B2-EphB4 signaling between PDLF and osteoblasts of
      the alveolar bone might contribute to osteogenesis at tension sites during
      orthodontic tooth movement.

PMID- 21880728
TI  - Cdc42 regulates extracellular matrix remodeling in three dimensions.
AB  - Extracellular matrix (ECM) actively participates in normal cell regulation and in
      the process of tumor progression. The Rho GTPase Cdc42 has been shown to regulate
      cell-ECM interaction in conventional two-dimensional culture conditions by using
      dominant mutants of Cdc42 in immortalized cell lines that may introduce
      nonspecific effects. Here, we employ three-dimensional culture systems for
      conditional gene targeted primary mouse embryonic fibroblasts that better
      simulate the reciprocal and adaptive interactions between cells and surrounding
      matrix to define the role of Cdc42 signaling pathways in ECM organization. Cdc42
      deficiency leads to a defect in global cell-matrix interactions reflected by a
      decrease in collagen gel contraction. The defect is associated with an altered
      cell-matrix interaction that is evident by morphologic changes and reduced focal
      adhesion complex formation. The matrix defect is also associated with a reduction
      in synthesis and activation of matrix metalloproteinase 9 (MMP9) and altered
      fibronectin deposition patterning. A Cdc42 mutant rescue experiment found that
      downstream of Cdc42, p21-activated kinase (PAK), but not Par6 or WASP, may be
      involved in regulating collagen gel contraction and fibronectin organization.
      Thus, in addition to the previously implicated roles in intracellular regulation
      of actin organization, proliferation, and vesicle trafficking, Cdc42 is essential
      in ECM remodeling in three dimensions.

PMID- 21880729
TI  - Regulation of fertility, survival, and cuticle collagen function by the
      Caenorhabditis elegans eaf-1 and ell-1 genes.
AB  - EAF2, an androgen-regulated protein, interacts with members of the ELL (eleven
      nineteen lysine-rich leukemia) transcription factor family and also acts as a
      tumor suppressor. Although these proteins control transcriptional elongation and
      perhaps modulate the effects of other transcription factors, the mechanisms of
      their actions remain largely unknown. To gain new insights into the biology of
      the EAF2 and ELL family proteins, we used Caenorhabditis elegans as a model to
      explore the in vivo roles of their worm orthologs. Through the use of transgenic
      worms, RNAi, and an eaf-1 mutant, we found that both genes are expressed in
      multiple cell types throughout the worm life cycle and that they play important
      roles in fertility, survival, and body size regulation. ELL-1 and EAF-1 likely
      contribute to these activities in part through modulating cuticle synthesis,
      given that we observed a disrupted cuticle structure in ell-1 RNAi-treated or eaf
      1 mutant worms. Consistent with disruption of cuticle structure, loss of either
      ELL-1 or EAF-1 suppressed the rol phenotype of specific collagen mutants,
      possibly through the control of dpy-3, dpy-13, and sqt-3 collagen gene
      expression. Furthermore, we also noted the regulation of collagen expression by
      ELL overexpression in PC3 human prostate cancer cells. Together, these results
      reveal important roles for the eaf-1 and ell-1 genes in the regulation of
      extracellular matrix components.

PMID- 21880730
TI  - Cooperative role of nectin-nectin and nectin-afadin interactions in formation of
      nectin-based cell-cell adhesion.
AB  - The nectin cell adhesion molecules interact in trans with each other through
      their extracellular regions and with afadin through their cytoplasmic tails,
      forming adherens junctions in cooperation with cadherins. In a single cell, Necl
      5 (nectin-like molecule-5) localizes at the leading edge and regulates
      directional cell movement in response to a chemoattractant. In such a single
      cell, afadin also localizes at the leading edge without interacting with nectins
      or Necl-5. It remains unknown how the nectin-nectin and nectin-afadin
      interactions are initiated when moving cells contact each other to initiate the
      formation of adherens junctions. We show here that the Necl-5-nectin interaction
      induced by cell-cell contact enhances the nectin-afadin interaction. This
      interaction then enhances the nectin-nectin interaction, which further enhances
      the nectin-afadin interaction in a positive feedback manner. Thus, the Necl-5
      nectin, nectin-nectin, and nectin-afadin interactions cooperatively increase the
      clustering of the nectin-afadin complex at the cell-cell contact sites, promoting
      the formation of the nectin-based cell-cell adhesion.

PMID- 21880731
TI  - Recognition of unmodified histone H3 by the first PHD finger of bromodomain-PHD
      finger protein 2 provides insights into the regulation of histone
      acetyltransferases monocytic leukemic zinc-finger protein (MOZ) and MOZ-related
      factor (MORF).
AB  - MOZ (monocytic leukemic zinc-finger protein) and MORF (MOZ-related factor) are
      histone acetyltransferases important for HOX gene expression as well as embryo
      and postnatal development. They form complexes with other regulatory subunits
      through the scaffold proteins BRPF1/2/3 (bromodomain-PHD (plant homeodomain)
      finger proteins 1, 2, or 3). BRPF proteins have multiple domains, including two
      PHD fingers, for potential interactions with histones. Here we show that the
      first PHD finger of BRPF2 specifically recognizes the N-terminal tail of
      unmodified histone H3 (unH3) and report the solution structures of this PHD
      finger both free and in complex with the unH3 peptide. Structural analysis
      revealed that the unH3 peptide forms a third antiparallel beta-strand that pairs
      with the PHD1 two-stranded antiparallel beta-sheet. The binding specificity was
      determined primarily through the recognition of arginine 2 and lysine 4 of the
      unH3 by conserved aspartic acids of PHD1 and of threonine 6 of the unH3 by a
      conserved asparagine. Isothermal titration calorimetry and NMR assays showed that
      post-translational modifications such as H3R2me2as, H3T3ph, H3K4me, H3K4ac, and
      H3T6ph antagonized the interaction between histone H3 and PHD1. Furthermore,
      histone binding by PHD1 was important for BRPF2 to localize to the HOXA9 locus in
      vivo. PHD1 is highly conserved in yeast NuA3 and other histone acetyltransferase
      complexes, so the results reported here also shed light on the function and
      regulation of these complexes.

PMID- 21880732
TI  - The chaperonin containing TCP1 complex (CCT/TRiC) is involved in mediating sperm
      oocyte interaction.
AB  - Sperm-oocyte interactions are among the most remarkable processes in cell
      biology. These cellular recognition events are initiated by an exquisitely
      specific adhesion of free-swimming spermatozoa to the zona pellucida, an
      acellular matrix that surrounds the ovulated oocyte. Decades of research focusing
      on this interaction have led to the establishment of a widely held paradigm that
      the zona pellucida receptor is a single molecular entity that is constitutively
      expressed on the sperm cell surface. In contrast, we have employed the techniques
      of blue native-polyacrylamide gel electrophoresis, far Western blotting, and
      proximity ligation to secure the first direct evidence in support of a novel
      hypothesis that zona binding is mediated by multimeric sperm receptor
      complex(es). Furthermore, we show that one such multimeric association,
      comprising the chaperonin-containing TCP1 complex (CCT/TRiC) and a zona-binding
      protein, zona pellucida-binding protein 2, is present on the surface of
      capacitated spermatozoa and could account for the zona binding activity of these
      cells. Collectively, these data provide an important biochemical insight into the
      molecular basis of sperm-zona pellucida interaction and a plausible explanation
      for how spermatozoa gain their ability to fertilize.

PMID- 21880733
TI  - ADAMTSL6beta protein rescues fibrillin-1 microfibril disorder in a Marfan
      syndrome mouse model through the promotion of fibrillin-1 assembly.
AB  - Marfan syndrome (MFS) is a systemic disorder of the connective tissues caused by
      insufficient fibrillin-1 microfibril formation and can cause cardiac
      complications, emphysema, ocular lens dislocation, and severe periodontal
      disease. ADAMTSL6beta (A disintegrin-like metalloprotease domain with
      thrombospondin type I motifs-like 6beta) is a microfibril-associated
      extracellular matrix protein expressed in various connective tissues that has
      been implicated in fibrillin-1 microfibril assembly. We here report that
      ADAMTSL6beta plays an essential role in the development and regeneration of
      connective tissues. ADAMTSL6beta expression rescues microfibril disorder after
      periodontal ligament injury in an MFS mouse model through the promotion of
      fibrillin-1 microfibril assembly. In addition, improved fibrillin-1 assembly in
      MFS mice following the administration of ADAMTSL6beta attenuates the
      overactivation of TGF-beta signals associated with the increased release of
      active TGF-beta from disrupted fibrillin-1 microfibrils within periodontal
      ligaments. Our current data thus demonstrate the essential contribution of
      ADAMTSL6beta to fibrillin-1 microfibril formation. These findings also suggest a
      new therapeutic strategy for the treatment of MFS through ADAMTSL6beta-mediated
      fibrillin-1 microfibril assembly.

PMID- 21880734
TI  - Local cytosolic Ca2+ elevations are required for stromal interaction molecule 1
      (STIM1) de-oligomerization and termination of store-operated Ca2+ entry.
AB  - The Ca(2+) depletion of the endoplasmic reticulum (ER) activates the ubiquitous
      store-operated Ca(2+) entry (SOCE) pathway that sustains long-term Ca(2+) signals
      critical for cellular functions. ER Ca(2+) depletion initiates the
      oligomerization of stromal interaction molecules (STIM) that control SOCE
      activation, but whether ER Ca(2+) refilling controls STIM de-oligomerization and
      SOCE termination is not known. Here, we correlate the changes in free luminal ER
      Ca(2+) concentrations ([Ca(2+)](ER)) and in STIM1 oligomerization, using
      fluorescence resonance energy transfer (FRET) between CFP-STIM1 and YFP-STIM1. We
      observed that STIM1 de-oligomerized at much lower [Ca(2+)](ER) levels during
      store refilling than it oligomerized during store depletion. We then refilled ER
      stores without adding exogenous Ca(2+) using a membrane-permeable Ca(2+) chelator
      to provide a large reservoir of buffered Ca(2+). This procedure rapidly restored
      pre-stimulatory [Ca(2+)](ER) levels but did not trigger STIM1 de-oligomerization,
      the FRET signals remaining elevated as long as the external [Ca(2+)] remained
      low. STIM1 dissociation evoked by Ca(2+) readmission was prevented by SOC channel
      inhibition and was associated with cytosolic Ca(2+) elevations restricted to
      STIM1 puncta, indicating that Ca(2+) acts on a cytosolic target close to STIM1
      clusters. These data indicate that the refilling of ER Ca(2+) stores is not
      sufficient to induce STIM1 de-oligomerization and that localized Ca(2+)
      elevations in the vicinity of assembled SOCE complexes are required for the
      termination of SOCE.

PMID- 21880735
TI  - Structure and mechanism of the lipooligosaccharide sialyltransferase from
      Neisseria meningitidis.
AB  - The first x-ray crystallographic structure of a CAZY family-52
      glycosyltransferase, that of the membrane associated alpha2,3/alpha2,6
      lipooligosaccharide sialyltransferase from Neisseria meningitidis serotype L1
      (NST), has been solved to 1.95 A resolution. The structure of NST adopts a GT-B
      fold common with other glycosyltransferase (GT) families but exhibits a novel
      domain swap of the N-terminal 130 residues to create a functional homodimeric
      form not observed in any other class to date. The domain swap is mediated at the
      structural level by a loop-helix-loop extension between residues Leu-108 and Met
      130 (we term the swapping module) and a unique lipid-binding domain. NST
      catalyzes the creation of alpha2,3- or 2,6-linked oligosaccharide products from a
      CMP-sialic acid (Neu5Ac) donor and galactosyl-containing acceptor sugars. Our
      structures of NST bound to the non-hydrolyzable substrate analog CMP-3F((axial))
      Neu5Ac show that the swapping module from one monomer of NST mediates the binding
      of the donor sugar in a composite active site formed at the dimeric interface.
      Kinetic analysis of designed point mutations observed in the CMP-3F((axial))
      Neu5Ac binding site suggests potential roles of a requisite general base (Asp
      258) and general acid (His-280) in the NST catalytic mechanism. A long
      hydrophobic tunnel adjacent to the dimer interface in each of the two monomers
      contains electron density for two extended linear molecules that likely belong to
      either the two fatty acyl chains of a diglyceride lipid or the two polyethylene
      glycol groups of the detergent Triton X-100. In this work, Triton X-100 maintains
      the activity and increases the solubility of NST during purification and is
      critical to the formation of ordered crystals. Together, the mechanistic
      implications of the NST structure provide insight into lipooligosaccharide
      sialylation with respect to the association of substrates and the essential
      membrane-anchored nature of NST on the bacterial surface.

PMID- 21880736
TI  - Cartilage intermediate layer protein 2 (CILP-2) is expressed in articular and
      meniscal cartilage and down-regulated in experimental osteoarthritis.
AB  - Using transcriptome profiling to determine differential gene expression between
      the permanent mouse articular cartilage and the transient growth plate cartilage,
      we identified a highly expressed gene, Cilp2, which is expressed differentially
      by articular chondrocytes. CILP-2 is highly homologous to CILP-1 (cartilage
      intermediate layer protein 1), which is expressed in the intermediate zone of
      articular cartilage and has been linked to cartilage degenerative diseases. We
      demonstrated that Cilp2 has a restricted mRNA distribution at the surface of the
      mouse articular cartilage during development, becoming localized to the
      intermediate zone of articular cartilage and meniscal cartilage with maturity.
      Although the extracellular CILP-2 protein localization is broadly similar to CILP
      1, CILP-2 appears to be more localized in the deeper intermediate zone of the
      articular cartilage extracellular matrix at maturity. CILP-2 was shown to be
      proteolytically processed, N-glycosylated, and present in human articular
      cartilage. In surgically induced osteoarthritis in mice, Cilp1 and Cilp2 gene
      expression was dysregulated. However, whereas Cilp1 expression was increased,
      Cilp2 gene expression was down-regulated demonstrating a differential response to
      mechanically induced joint destabilization. CILP-2 protein was reduced in the
      mouse osteoarthritic cartilage. Ultrastructural analysis also suggested that CILP
      2 may be associated with collagen VI microfibrils and thus may mediate
      interactions between matrix components in the territorial and inter-territorial
      articular cartilage matrix. mRNA expression analysis indicated that whereas Cilp1
      and Cilp2 are expressed most abundantly in cartilaginous tissues, expression can
      be detected in muscle and heart.

PMID- 21880737
TI  - Endothelial cell migration on fibronectin is regulated by syntaxin 6-mediated
      alpha5beta1 integrin recycling.
AB  - The alpha5beta1 integrin heterodimer regulates many processes that contribute to
      embryonic development and angiogenesis, in both physiological and pathological
      contexts. As one of the major adhesion complexes on endothelial cells, it plays a
      vital role in adhesion and migration along the extracellular matrix. We recently
      showed that angiogenesis is modulated by syntaxin 6, a Golgi- and endosome
      localized t-SNARE, and that it does so by regulating the post-Golgi trafficking
      of VEGFR2. Here we show that syntaxin 6 is also required for alpha5beta1 integrin
      mediated adhesion of endothelial cells to, and migration along, fibronectin. We
      demonstrate that syntaxin 6 and alpha5beta1 integrin colocalize in EEA1
      containing early endosomes, and that functional inhibition of syntaxin 6 leads to
      misrouting of beta1 integrin to the degradation pathway (late endosomes and
      lysosomes) rather transport along recycling pathway from early endosomes; an
      increase in the pool of ubiquitinylated alpha5 integrin and its lysosome
      dependent degradation; reduced cell spreading on fibronectin; decreased Rac1
      activation; and altered Rac1 localization. Collectively, our data show that
      functional syntaxin 6 is required for the regulation of alpha5beta1-mediated
      endothelial cell movement on fibronectin. These syntaxin 6-regulated membrane
      trafficking events control outside-in signaling via haptotactic and chemotactic
      mechanisms.

PMID- 21880738
TI  - Mixed lineage kinase 3 modulates beta-catenin signaling in cancer cells.
AB  - Expression of beta-catenin is strictly regulated in normal cells via the glycogen
      synthase kinase 3beta (GSK3beta)- adenomatous polyposis coli-axin-mediated
      degradation pathway. Mechanisms leading to inactivation of this pathway (example:
      activation of Wnt/beta-catenin signaling or mutations of members of the
      degradation complex) can result in beta-catenin stabilization and activation of
      beta-catenin/T-cell factor (TCF) signaling. beta-Catenin-mediated cellular events
      are diverse and complex. A better understanding of the cellular signaling
      networks that control beta-catenin pathway is important for designing effective
      therapeutic strategies targeting this axis. To gain more insight, we focused on
      determining any possible cross-talk between beta-catenin and mixed lineage kinase
      3 (MLK3), a MAPK kinase kinase member. Our studies indicated that MLK3 can induce
      beta-catenin expression via post-translational stabilization in various cancer
      cells, including prostate cancer. This function of MLK3 was dependent on its
      kinase activity. MLK3 can interact with beta-catenin and phosphorylate it in
      vitro. Overexpression of GSK3beta-WT or the S9A mutant was unable to antagonize
      MLK3-induced stabilization, suggesting this to be independent of GSK3beta
      pathway. Surprisingly, despite stabilizing beta-catenin, MLK3 inhibited TCF
      transcriptional activity in the presence of both WT and S37A beta-catenin. These
      resulted in reduced expression of beta-catenin/TCF downstream targets Survivin
      and myc. Immunoprecipitation studies indicated that MLK3 did not decrease beta
      catenin/TCF interaction but promoted interaction between beta-catenin and KLF4, a
      known repressor of beta-catenin/TCF transcriptional activity. In addition, co
      expression of MLK3 and beta-catenin resulted in significant G(2)/M arrest. These
      studies provide a novel insight toward the regulation of beta-catenin pathway,
      which can be targeted to control cancer cell proliferation, particularly those
      with aberrant activation of beta-catenin signaling.

PMID- 21880739
TI  - G protein-coupled receptors and resistance to inhibitors of cholinesterase-8A
      (Ric-8A) both regulate the regulator of g protein signaling 14 RGS14.Galphai1
      complex in live cells.
AB  - Regulator of G protein Signaling 14 (RGS14) is a multifunctional scaffolding
      protein that integrates both conventional and unconventional G protein signaling
      pathways. Like other RGS (regulator of G protein signaling) proteins, RGS14 acts
      as a GTPase accelerating protein to terminate conventional Galpha(i/o) signaling.
      However, unlike other RGS proteins, RGS14 also contains a G protein
      regulatory/GoLoco motif that specifically binds Galpha(i1/3)-GDP in cells and in
      vitro. The non-receptor guanine nucleotide exchange factor Ric-8A can bind and
      act on the RGS14.Galpha(i1)-GDP complex to play a role in unconventional G
      protein signaling independent of G protein-coupled receptors (GPCRs). Here we
      demonstrate that RGS14 forms a Galpha(i/o)-dependent complex with a G(i)-linked
      GPCR and that this complex is regulated by receptor agonist and Ric-8A
      (resistance to inhibitors of cholinesterase-8A). Using live cell bioluminescence
      resonance energy transfer, we show that RGS14 functionally associates with the
      alpha(2A)-adrenergic receptor (alpha(2A)-AR) in a Galpha(i/o)-dependent manner.
      This interaction is markedly disrupted after receptor stimulation by the specific
      agonist UK14304, suggesting complex dissociation or rearrangement. Agonist
      mediated dissociation of the RGS14.alpha(2A)-AR complex occurs in the presence of
      Galpha(i/o) but not Galpha(s) or Galpha(q). Unexpectedly, RGS14 does not
      dissociate from Galpha(i1) in the presence of stimulated alpha(2A)-AR, suggesting
      preservation of RGS14.Galpha(i1) complexes after receptor activation. However,
      Ric-8A facilitates dissociation of both the RGS14.Galpha(i1) complex and the
      Galpha(i1)-dependent RGS14.alpha(2A)-AR complex after receptor activation.
      Together, these findings indicate that RGS14 can form complexes with GPCRs in
      cells that are dependent on Galpha(i/o) and that these RGS14.Galpha(i1).GPCR
      complexes may be substrates for other signaling partners such as Ric-8A.

PMID- 21880740
TI  - Assembly mechanism of FCT region type 1 pili in serotype M6 Streptococcus
      pyogenes.
AB  - The human pathogen Streptococcus pyogenes produces diverse pili depending on the
      serotype. We investigated the assembly mechanism of FCT type 1 pili in a serotype
      M6 strain. The pili were found to be assembled from two precursor proteins, the
      backbone protein T6 and ancillary protein FctX, and anchored to the cell wall in
      a manner that requires both a housekeeping sortase enzyme (SrtA) and pilus
      associated sortase enzyme (SrtB). SrtB is primarily required for efficient
      formation of the T6 and FctX complex and subsequent polymerization of T6, whereas
      proper anchoring of the pili to the cell wall is mainly mediated by SrtA. Because
      motifs essential for polymerization of pilus backbone proteins in other Gram
      positive bacteria are not present in T6, we sought to identify the functional
      residues involved in this process. Our results showed that T6 encompasses the
      novel VAKS pilin motif conserved in streptococcal T6 homologues and that the
      lysine residue (Lys-175) within the motif and cell wall sorting signal of T6 are
      prerequisites for isopeptide linkage of T6 molecules. Because Lys-175 and the
      cell wall sorting signal of FctX are indispensable for substantial incorporation
      of FctX into the T6 pilus shaft, FctX is suggested to be located at the pilus
      tip, which was also implied by immunogold electron microscopy findings. Thus, the
      elaborate assembly of FCT type 1 pili is potentially organized by sortase
      mediated cross-linking between sorting signals and the amino group of Lys-175
      positioned in the VAKS motif of T6, thereby displaying T6 and FctX in a
      temporospatial manner.

PMID- 21880741
TI  - Nuclear factor of activated T cells (NFAT) proteins repress canonical Wnt
      signaling via its interaction with Dishevelled (Dvl) protein and participate in
      regulating neural progenitor cell proliferation and differentiation.
AB  - The Ca(2+) signaling pathway appears to regulate the processes of the early
      development through its antagonism of canonical Wnt/beta-catenin signaling
      pathway. However, the underlying mechanism is still poorly understood. Here, we
      show that nuclear factor of activated T cells (NFAT), a component of Ca(2+)
      signaling, interacts directly with Dishevelled (Dvl) in a Ca(2+)-dependent
      manner. A dominant negative form of NFAT rescued the inhibition of the Wnt/beta
      catenin pathway triggered by the Ca(2+) signal. NFAT functioned downstream of
      beta-catenin without interfering with its stability, but influencing the
      interaction of beta-catenin with Dvl by its competitively binding to Dvl.
      Furthermore, we demonstrate that NFAT is a regulator in the proliferation and
      differentiation of neural progenitor cells by modulating canonical Wnt/beta
      catenin signaling pathway in the neural tube of chick embryo. Our findings
      suggest that NFAT negatively regulates canonical Wnt/beta-catenin signaling by
      binding to Dvl, thereby participating in vertebrate neurogenesis.

PMID- 21880742
TI  - Molecular basis of the gamma-aminobutyric acid A receptor alpha3 subunit
      interaction with the clustering protein gephyrin.
AB  - The multifunctional scaffolding protein gephyrin is a key player in the formation
      of the postsynaptic scaffold at inhibitory synapses, clustering both inhibitory
      glycine receptors (GlyRs) and selected GABA(A) receptor (GABA(A)R) subtypes. We
      report a direct interaction between the GABA(A)R alpha3 subunit and gephyrin,
      mapping reciprocal binding sites using mutagenesis, overlay, and yeast two-hybrid
      assays. This analysis reveals that critical determinants of this interaction are
      located in the motif FNIVGTTYPI in the GABA(A)R alpha3 M3-M4 domain and the motif
      SMDKAFITVL at the N terminus of the gephyrin E domain. GABA(A)R alpha3 gephyrin
      binding-site mutants were unable to co-localize with endogenous gephyrin in
      transfected hippocampal neurons, despite being able to traffic to the cell
      membrane and form functional benzodiazepine-responsive GABA(A)Rs in recombinant
      systems. Interestingly, motifs responsible for interactions with GABA(A)R alpha2,
      GABA(A)R alpha3, and collybistin on gephyrin overlap. Curiously, two key residues
      (Asp-327 and Phe-330) in the GABA(A)R alpha2 and alpha3 binding sites on gephyrin
      also contribute to GlyR beta subunit-E domain interactions. However, isothermal
      titration calorimetry reveals a 27-fold difference in the interaction strength
      between GABA(A)R alpha3 and GlyR beta subunits with gephyrin with dissociation
      constants of 5.3 MUm and 0.2 MUm, respectively. Taken together, these
      observations suggest that clustering of GABA(A)R alpha2, alpha3, and GlyRs by
      gephyrin is mediated by distinct mechanisms at mixed glycinergic/GABAergic
      synapses.

PMID- 21880743
TI  - Identification of human endogenous retrovirus-specific T cell responses in
      vertically HIV-1-infected subjects.
AB  - Human endogenous retrovirus (HERV)-specific T cell responses in HIV-1-infected
      adults have been reported. Whether HERV-specific immunity exists in vertically
      HIV-1-infected children is unknown. We performed a cross-sectional analysis of
      HERV-specific T cell responses in 42 vertically HIV-1-infected children. HERV (
      H, -K, and -L family)-specific T cell responses were identified in 26 of 42
      subjects, with the greatest magnitude observed for the responses to HERV-L. These
      HERV-specific T cell responses were inversely correlated with the HIV-1 plasma
      viral load and positively correlated with CD4(+) T cell counts. These data
      indicate that HERV-specific T cells may participate in controlling HIV-1
      replication and that certain highly conserved HERV-derived proteins may serve as
      promising therapeutic vaccine targets in HIV-1-infected children.

PMID- 21880744
TI  - The M segment of the 2009 new pandemic H1N1 influenza virus is critical for its
      high transmission efficiency in the guinea pig model.
AB  - A remarkable feature of the 2009 pandemic H1N1 influenza virus is its efficient
      transmissibility in humans compared to that of precursor strains from the triple
      reassortant swine influenza virus lineage, which cause only sporadic infections
      in humans. The viral components essential for this phenotype have not been fully
      elucidated. In this study, we aimed to determine the viral factors critical for
      aerosol transmission of the 2009 pandemic virus. Single or multiple segment
      reassortments were made between the pandemic A/California/04/09 (H1N1) (Cal/09)
      virus and another H1N1 strain, A/Puerto Rico/8/34 (H1N1) (PR8). These viruses
      were then tested in the guinea pig model to understand which segment of Cal/09
      virus conferred transmissibility to the poorly transmissible PR8 virus. We
      confirmed our findings by generating recombinant A/swine/Texas/1998 (H3N2)
      (sw/Tx/98) virus, a representative triple-reassortant swine virus, containing
      segments of the Cal/09 virus. The data showed that the M segment of the Cal/09
      virus promoted aerosol transmissibility to recombinant viruses with PR8 and
      sw/Tx/98 virus backgrounds, suggesting that the M segment is a critical factor
      supporting the transmission of the 2009 pandemic virus.

PMID- 21880745
TI  - Role of the two sialic acid binding sites on the newcastle disease virus HN
      protein in triggering the interaction with the F protein required for the
      promotion of fusion.
AB  - Newcastle disease virus (NDV)-induced membrane fusion requires an interaction
      between the hemagglutinin-neuraminidase (HN) attachment and the fusion (F)
      proteins, triggered by HN's binding to receptors. NDV HN has two sialic acid
      binding sites: site I, which also mediates neuraminidase activity, and site II,
      which straddles the membrane-distal end of the dimer interface. By characterizing
      the effect on receptor binding avidity and F-interactive capability of HN dimer
      interface mutations, we present evidence consistent with (i) receptor engagement
      by site I triggering the interaction with F and (ii) site II functioning to
      maintain high-avidity receptor binding during the fusion process.

PMID- 21880746
TI  - Role of peroxisome proliferator-activated receptor gamma coactivator 1alpha in
      AKT/PKB-mediated inhibition of hepatitis B virus biosynthesis.
AB  - Hepatitis B virus (HBV) transcription and replication are essentially restricted
      to hepatocytes because liver-enriched transcription factors govern viral RNA
      synthesis. The level of transcription from the HBV promoters depends on both the
      transcription factors binding to these regulatory sequence elements and their
      ability to recruit coactivators capable of mediating assembly of the
      transcription preinitiation complex containing RNA polymerase II. Nuclear
      receptors are a primary determinant of HBV pregenomic RNA synthesis and, hence,
      viral replication. Peroxisome proliferator-activated receptor gamma coactivator
      1alpha (PGC1alpha) enhances the activity of nuclear receptors and, consequently,
      HBV biosynthesis. PGC1alpha is also an important target of signal transduction
      pathways involved in hepatic glucose and lipid homeostasis, suggesting that this
      coactivator may have an important role in modulating HBV biosynthesis under
      various physiological conditions. Consistent with this suggestion, v-akt murine
      thymoma viral oncogene homolog/protein kinase B (AKT/PKB) is shown to modulate
      PGC1alpha activity and, hence, HBV transcription and replication in a cell line
      specific manner. In addition, AKT can modulate HBV replication in some but not
      all cell lines at a posttranscriptional step in the viral life cycle. These
      observations demonstrate that growth and nutritional signals have the capacity to
      influence viral production, but the magnitude of these effects will depend on the
      precise cellular context in which they occur.

PMID- 21880747
TI  - The encapsidated genome of Microplitis demolitor bracovirus integrates into the
      host Pseudoplusia includens.
AB  - Polydnaviruses (PDVs) are symbionts of parasitoid wasps that function as gene
      delivery vehicles in the insects (hosts) that the wasps parasitize. PDVs persist
      in wasps as integrated proviruses but are packaged as circularized and segmented
      double-stranded DNAs into the virions that wasps inject into hosts. In contrast,
      little is known about how PDV genomic DNAs persist in host cells. Microplitis
      demolitor carries Microplitis demolitor bracovirus (MdBV) and parasitizes the
      host Pseudoplusia includens. MdBV infects primarily host hemocytes and also
      infects a hemocyte-derived cell line from P. includens called CiE1 cells. Here we
      report that all 15 genomic segments of the MdBV encapsidated genome exhibited
      long-term persistence in CiE1 cells. Most MdBV genes expressed in hemocytes were
      persistently expressed in CiE1 cells, including members of the glc gene family
      whose products transformed CiE1 cells into a suspension culture. PCR-based
      integration assays combined with cloning and sequencing of host-virus junctions
      confirmed that genomic segments J and C persisted in CiE1 cells by integration.
      These genomic DNAs also rapidly integrated into parasitized P. includens.
      Sequence analysis of wasp-viral junction clones showed that the integration of
      proviral segments in M. demolitor was associated with a wasp excision/integration
      motif (WIM) known from other bracoviruses. However, integration into host cells
      occurred in association with a previously unknown domain that we named the host
      integration motif (HIM). The presence of HIMs in most MdBV genomic DNAs suggests
      that the integration of each genomic segment into host cells occurs through a
      shared mechanism.

PMID- 21880748
TI  - Identification of Autographa californica nucleopolyhedrovirus ac93 as a core gene
      and its requirement for intranuclear microvesicle formation and nuclear egress of
      nucleocapsids.
AB  - Autographa californica nucleopolyhedrovirus (AcMNPV) orf93 (ac93) is a highly
      conserved uncharacterized gene that is found in all of the sequenced baculovirus
      genomes except for Culex nigripalpus NPV. In this report, using bioinformatics
      analyses, ac93 and odv-e25 (ac94) were identified as baculovirus core genes and
      thus p33-ac93-odv-e25 represent a cluster of core genes. To investigate the role
      of ac93 in the baculovirus life cycle, an ac93 knockout AcMNPV bacmid was
      constructed via homologous recombination in Escherichia coli. Fluorescence and
      light microscopy showed that the AcMNPV ac93 knockout did not spread by
      infection, and titration assays confirmed a defect in budded virus (BV)
      production. However, deletion of ac93 did not affect viral DNA replication.
      Electron microscopy indicated that ac93 was required for the egress of
      nucleocapsids from the nucleus and the formation of intranuclear microvesicles,
      which are precursor structures of occlusion-derived virus (ODV) envelopes.
      Immunofluorescence analyses showed that Ac93 was concentrated toward the
      cytoplasmic membrane in the cytoplasm and in the nuclear ring zone in the
      nucleus. Western blot analyses showed that Ac93 was associated with both
      nucleocapsid and envelope fractions of BV, but only the nucleocapsid fraction of
      ODV. Our results suggest that ac93, although not previously recognized as a core
      gene, is one that plays an essential role in the formation of the ODV envelope
      and the egress of nucleocapsids from the nucleus.

PMID- 21880749
TI  - Host-soluble galectin-1 promotes HIV-1 replication through a direct interaction
      with glycans of viral gp120 and host CD4.
AB  - Sexual transmission of HIV-1 requires virus adsorption to a target cell,
      typically a CD4(+) T lymphocyte residing in the lamina propria, beneath the
      epithelium. To escape the mucosal clearance system and reach its target cells,
      HIV-1 has evolved strategies to circumvent deleterious host factors. Galectin-1,
      a soluble lectin found in the underlayers of the epithelium, increases HIV-1
      infectivity by accelerating its binding to susceptible cells. By comparison,
      galectin-3, a family member expressed by epithelial cells and part of the mucosal
      clearance system, does not perform similarly. We show here that galectin-1
      directly binds to HIV-1 in a beta-galactoside-dependent fashion through
      recognition of clusters of N-linked glycans on the viral envelope gp120.
      Unexpectedly, this preferential binding of galectin-1 does not rely on the
      primary sequence of any particular glycans. Instead, glycan clustering arising
      from the tertiary structure of gp120 hinders its binding by galectin-3. Increased
      polyvalency of a specific ligand epitope is a common strategy for glycans to
      increase their avidity for lectins. In this peculiar occurrence, glycan
      clustering is instead exploited to prevent binding of gp120 by galectin-3, which
      would lead to a biological dead-end for the virus. Our data also suggest that
      galectin-1 binds preferentially to CD4, the host receptor for gp120. Together,
      these results suggest that HIV-1 exploits galectin-1 to enhance gp120-CD4
      interactions, thereby promoting virus attachment and infection events. Since
      viral adhesion is a rate-limiting step for HIV-1 entry, modulation of the gp120
      interaction with galectin-1 could thus represent a novel approach for the
      prevention of HIV-1 transmission.

PMID- 21880750
TI  - Tissue tropism of swine influenza viruses and reassortants in ex vivo cultures of
      the human respiratory tract and conjunctiva.
AB  - The 2009 pandemic influenza H1N1 (H1N1pdm) virus was generated by reassortment of
      swine influenza viruses of different lineages. This was the first influenza
      pandemic to emerge in over 4 decades and the first to occur after the realization
      that influenza pandemics arise from influenza viruses of animals. In order to
      understand the biological determinants of pandemic emergence, it is relevant to
      compare the tropism of different lineages of swine influenza viruses and
      reassortants derived from them with that of 2009 pandemic H1N1 (H1N1pdm) and
      seasonal influenza H1N1 viruses in ex vivo cultures of the human nasopharynx,
      bronchus, alveoli, and conjunctiva. We hypothesized that virus which can transmit
      efficiently between humans replicated well in the human upper airways. As
      previously reported, H1N1pdm and seasonal H1N1 viruses replicated efficiently in
      the nasopharyngeal, bronchial, and alveolar epithelium. In contrast,
      representative viruses from the classical swine (CS) (H1N1) lineage could not
      infect human respiratory epithelium; Eurasian avian-like swine (EA) (H1N1)
      viruses only infected alveolar epithelium and North American triple-reassortant
      (TRIG) viruses only infected the bronchial epithelium albeit inefficiently.
      Interestingly, a naturally occurring triple-reassortant swine virus,
      A/SW/HK/915/04 (H1N2), with a matrix gene segment of EA swine derivation (i.e.,
      differing from H1N1pdm only in lacking a neuraminidase [NA] gene of EA
      derivation) readily infected and replicated in human nasopharyngeal and bronchial
      epithelia but not in the lung. A recombinant sw915 with the NA from H1N1pdm
      retained its tropism for the bronchus and acquired additional replication
      competence for alveolar epithelium. In contrast to H1N1pdm, none of the swine
      viruses tested nor seasonal H1N1 had tropism in human conjunctiva. Recombinant
      viruses generated by swapping the surface proteins (hemagglutinin and NA) of
      H1N1pdm and seasonal H1N1 virus demonstrated that these two gene segments
      together are key determinants of conjunctival tropism. Overall, these findings
      suggest that ex vivo cultures of the human respiratory tract provide a useful
      biological model for assessing the human health risk of swine influenza viruses.

PMID- 21880751
TI  - A physical link between the pseudorabies virus capsid and the nuclear egress
      complex.
AB  - Following their assembly, herpesvirus capsids exit the nucleus by budding at the
      inner nuclear membrane. Two highly conserved viral proteins are required for this
      process, pUL31 and pUL34. In this report, we demonstrate that the pUL31 component
      of the pseudorabies virus nuclear egress complex is a conditional capsid-binding
      protein that is unmasked in the absence of pUL34. The interaction between pUL31
      and capsids was confirmed through fluorescence microscopy and Western blot
      analysis of purified intranuclear capsids. Three viral proteins were tested for
      their abilities to mediate the pUL31-capsid interaction: the minor capsid protein
      pUL25, the portal protein pUL6, and the terminase subunit pUL33. Despite the
      requirement for each protein in nuclear egress, none of these viral proteins were
      required for the pUL31-capsid interaction. These findings provide the first
      formal evidence that a herpesvirus nuclear egress complex interacts with capsids
      and have implications for how DNA-containing capsids are selectively targeted for
      nuclear egress.

PMID- 21880752
TI  - Human cytomegalovirus glycoprotein gO complexes with gH/gL, promoting
      interference with viral entry into human fibroblasts but not entry into
      epithelial cells.
AB  - A complex of five human cytomegalovirus virus (HCMV) proteins, gH, gL, UL128,
      UL130, and UL131 (gH/gL/UL128-131), is essential for virus entry into epithelial
      cells. We previously showed that gH/gL/UL128-131 expressed in epithelial cells
      interferes with subsequent HCMV entry into cells. There was no interference with
      only gH/gL or gB. We concluded that the expression of gH/gL/UL128-131 causes a
      mislocalization or downregulation of epithelial cell proteins that HCMV requires
      for entry. In contrast, gH/gL/UL128-131 expression in fibroblasts did not produce
      interference, suggesting a different mechanism for entry. Here, we show that the
      coexpression of another HCMV glycoprotein, gO, with gH/gL in human fibroblasts
      interferes with HCMV entry into fibroblasts but not epithelial cells. However,
      the coexpression of gO with gH/gL did not increase the cell surface expression
      level of gH/gL and did not enhance cell-cell fusion, a process that depends upon
      cell surface gH/gL. Instead, gO promoted the export of gH/gL from the endoplasmic
      reticulum (ER) and the accumulation of gH/gL in the trans-Golgi network. Thus,
      interference with gH/gL or gH/gL/gO, i.e., the mislocalization or blocking of
      entry mediators, occurs in cytoplasmic membranes and not in cell surface
      membranes of fibroblasts. Together, the results provide additional support for
      our hypotheses that epithelial cells express putative gH/gL/UL128-1331 receptors
      important for HCMV entry and that fibroblasts express distinct gH/gL receptors.

PMID- 21880753
TI  - Kaposi's sarcoma-associated herpesvirus Rta tetramers make high-affinity
      interactions with repetitive DNA elements in the Mta promoter to stimulate DNA
      binding of RBP-Jk/CSL.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8
      [HHV-8]) is the etiologic agent of Kaposi's sarcoma (KS) and lymphoproliferative
      diseases. We previously demonstrated that the KSHV lytic switch protein Rta
      stimulates DNA binding of the cellular RBP-Jk/CSL protein, the nuclear component
      of the Notch pathway, on Rta target promoters. In the current study, we define
      the promoter requirements for formation of transcriptionally productive Rta/RBP
      Jk/DNA complexes. We show that highly pure Rta footprints 7 copies of a
      previously undescribed repetitive element in the promoter of the essential KSHV
      Mta gene. We have termed this element the "CANT repeat." CANT repeats are found
      on both strands of DNA and have a consensus sequence of ANTGTAACANT(A/T)(A/T)T.
      We demonstrate that Rta tetramers make high-affinity interactions (i.e., nM) with
      64 bp of the Mta promoter but not single CANT units. The number of CANT repeats,
      their presence in palindromes, and their positions relative to the RBP-Jk binding
      site determine the optimal target for Rta stimulation of RBP-Jk DNA binding and
      formation of ternary Rta/RBP-Jk/DNA complexes. DNA binding and tetramerization
      mutants of Rta fail to stimulate RBP-Jk DNA binding. Our chromatin
      immunoprecipitation assays show that RBP-Jk DNA binding is broadly, but
      selectively, stimulated across the entire KSHV genome during reactivation. We
      propose a model in which tetramerization of Rta allows it to straddle RBP-Jk and
      contact repeat units on both sides of RBP-Jk. Our study integrates high-affinity
      Rta DNA binding with the requirement for a cellular transcription factor in Rta
      transactivation.

PMID- 21880754
TI  - Lassa virus nucleoprotein mutants generated by reverse genetics induce a robust
      type I interferon response in human dendritic cells and macrophages.
AB  - Lassa virus (LASV; Arenaviridae) is responsible for severe hemorrhagic fevers in
      Africa. LASV nucleoprotein (NP) plays important roles in regulating viral
      transcription and replication and in inhibiting type I interferon (IFN)
      production. The NP C-terminal domain contains a 3'-to-5' exonuclease activity
      involved in suppressing IFN induction. We have established a murine polymerase
      (Pol) I reverse genetics system for LASV, showing that residues D389 and G392 of
      NP were critical for LASV viability, while the D389A/G392A and D389T/392A double
      mutants were severely altered in the ability to suppress IFN in macrophages and
      dendritic cells. Assessing their attenuation in vivo may open new perspectives in
      vaccinology.

PMID- 21880755
TI  - Annual vaccination against influenza virus hampers development of virus-specific
      CD8+ T cell immunity in children.
AB  - Infection with seasonal influenza A viruses induces immunity to potentially
      pandemic influenza A viruses of other subtypes (heterosubtypic immunity). We
      recently demonstrated that vaccination against seasonal influenza prevented the
      induction of heterosubtypic immunity against influenza A/H5N1 virus induced by
      infection with seasonal influenza in animal models, which correlated with the
      absence of virus-specific CD8(+) T cell responses. Annual vaccination of all
      healthy children against influenza has been recommended, but the impact of
      vaccination on the development of the virus-specific CD8(+) T cell immunity in
      children is currently unknown. Here we compared the virus-specific CD8(+) T cell
      immunity in children vaccinated annually with that in unvaccinated children. In
      the present study, we compared influenza A virus-specific cellular and humoral
      responses of unvaccinated healthy control children with those of children with
      cystic fibrosis (CF) who were vaccinated annually. Similar virus-specific CD4(+)
      T cell and antibody responses were observed, while an age-dependent increase of
      the virus-specific CD8(+) T cell response that was absent in vaccinated CF
      children was observed in unvaccinated healthy control children. Our results
      indicate that annual influenza vaccination is effective against seasonal
      influenza but hampers the development of virus-specific CD8(+) T cell responses.
      The consequences of these findings are discussed in the light of the development
      of protective immunity to seasonal and future pandemic influenza viruses.

PMID- 21880756
TI  - Compensatory mutations restore the replication defects caused by cytotoxic T
      lymphocyte escape mutations in hepatitis C virus polymerase.
AB  - While human leukocyte antigen B57 (HLA-B57) is associated with the spontaneous
      clearance of hepatitis C virus (HCV), the mechanisms behind this control remain
      unclear. Immunodominant CD8(+) T cell responses against the B57-restricted
      epitopes comprised of residues 2629 to 2637 of nonstructural protein 5B
      (NS5B(2629-2637)) (KSKKTPMGF) and E2(541-549) (NTRPPLGNW) were recently shown to
      be crucial in the control of HCV infection. Here, we investigated whether the
      selection of deleterious cytotoxic T lymphocyte (CTL) escape mutations in the
      NS5B KSKKTPMGF epitope might impair viral replication and contribute to the B57
      mediated control of HCV. Common CTL escape mutations in this epitope were
      identified from a cohort of 374 HCV genotype 1a-infected subjects, and their
      impact on HCV replication assessed using a transient HCV replicon system. We
      demonstrate that while escape mutations at residue 2633 (position 5) of the
      epitope had little or no impact on HCV replication in vitro, mutations at residue
      2629 (position 1) substantially impaired replication. Notably, the deleterious
      mutations at position 2629 were tightly linked in vivo to upstream mutations at
      residue 2626, which functioned to restore the replicative defects imparted by the
      deleterious escape mutations. These data suggest that the selection of costly
      escape mutations within the immunodominant NS5B KSKKTPMGF epitope may contribute
      in part to the control of HCV replication in B57-positive individuals and that
      persistence of HCV in B57-positive individuals may involve the development of
      specific secondary compensatory mutations. These findings are reminiscent of the
      selection of deleterious CTL escape and compensatory mutations by HLA-B57 in HIV
      1 infection and, thus, may suggest a common mechanism by which alleles like HLA
      B57 mediate protection against these highly variable pathogens.

PMID- 21880757
TI  - The interferon-inducible gene viperin restricts West Nile virus pathogenesis.
AB  - Type I interferon (IFN) signaling coordinates an early antiviral program in
      infected and uninfected cells by inducing IFN-stimulated genes (ISGs) that
      modulate viral entry, replication, and assembly. However, the specific antiviral
      functions in vivo of most ISGs remain unknown. Here, we examined the contribution
      of the ISG viperin to the control of West Nile virus (WNV) in genetically
      deficient cells and mice. While modest increases in levels of WNV replication
      were observed for primary viperin(-/-) macrophages and dendritic cells, no
      appreciable differences were detected in deficient embryonic cortical neurons or
      fibroblasts. In comparison, viperin(-/-) adult mice infected with WNV via the
      subcutaneous or intracranial route showed increased lethality and/or enhanced
      viral replication in central nervous system (CNS) tissues. In the CNS, viperin
      expression was induced in both WNV-infected and adjacent uninfected cells,
      including activated leukocytes at the site of infection. Our experiments suggest
      that viperin restricts the infection of WNV in a tissue- and cell-type-specific
      manner and may be an important ISG for controlling viral infections that cause
      CNS disease.

PMID- 21880758
TI  - A fusion-loop antibody enhances the infectious properties of immature flavivirus
      particles.
AB  - Flavivirus-infected cells secrete a mixture of mature, partially immature, and
      fully immature particles into the extracellular space. Although mature virions
      are highly infectious, prM-containing fully immature virions are noninfectious
      largely because the prM protein inhibits the cell attachment and fusogenic
      properties of the virus. If, however, cell attachment and entry are facilitated
      by anti-prM antibodies, immature flavivirus becomes infectious after efficient
      processing of the prM protein by the endosomal protease furin. A recent study
      demonstrated that E53, a cross-reactive monoclonal antibody (MAb) that engages
      the highly conserved fusion-loop peptide within the flavivirus envelope
      glycoprotein, preferentially binds to immature flavivirus particles. We
      investigated here the infectious potential of fully immature West Nile virus
      (WNV) and dengue virus (DENV) particles opsonized with E53 MAb and observed that,
      like anti-prM antibodies, this anti-E antibody also has the capacity to render
      fully immature flaviviruses infectious. E53-mediated enhancement of both immature
      WNV and DENV depended on efficient cell entry and the enzymatic activity of the
      endosomal furin. Furthermore, we also observed that E53-opsonized immature DENV
      particles but not WNV particles required a more acidic pH for efficient cleavage
      of prM by furin, adding greater complexity to the dynamics of antibody-mediated
      infection of immature flavivirus virions.

PMID- 21880759
TI  - The infectivity of prM-containing partially mature West Nile virus does not
      require the activity of cellular furin-like proteases.
AB  - Cleavage of the flavivirus prM protein by a cellular furin-like protease is a
      hallmark of virion maturation. While this cleavage is a required step in the
      viral life cycle, it can be inefficient. Virions that retain uncleaved prM may be
      infectious. We investigated whether cleavage by furin of prM on partially mature
      West Nile virus (WNV) during virus entry contributes to infectivity. Using
      quantitative assays of WNV infection, we found that virions incorporating
      considerable amounts of uncleaved prM protein were insensitive to treatment of
      cells with a potent inhibitor of furin activity. Thus, partially mature WNV does
      not require furin-like proteases for infectivity.

PMID- 21880760
TI  - Infection of calves with bovine norovirus GIII.1 strain Jena virus: an
      experimental model to study the pathogenesis of norovirus infection.
AB  - The experimental infection of newborn calves with bovine norovirus was used as a
      homologous large animal model to study the pathogenesis of norovirus infection
      and to determine target cells for viral replication. Six newborn calves were
      inoculated orally with Jena virus (JV), a bovine norovirus GIII.1 strain, and six
      calves served as mock-inoculated controls. Following infection, calves were
      euthanized before the onset of diarrhea (12 h postinoculation [hpi]), shortly
      after the onset of diarrhea (18 to 21 hpi), and postconvalescence (4 days pi
      [dpi]). Calves inoculated with JV developed severe watery diarrhea at 14 to 16
      hpi, and this symptom lasted for 53.5 to 67.0 h. Intestinal lesions were
      characterized by severe villus atrophy together with loss and attenuation of
      villus epithelium. Viral capsid antigen (JV antigen) was detected by
      immunohistochemistry in the cytoplasm of epithelial cells on villi. In addition,
      granular material positive for JV antigen was detected in the lamina propria of
      villi. Lesions first appeared at 12 hpi and were most extensive at 18 to 19 hpi,
      extending from midjejunum to ileum. The intestinal mucosa had completely
      recovered at 4 dpi. There was no indication of systemic infection as described
      for norovirus infection in mice. JV was found in intestinal contents by reverse
      transcription-PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) as early
      as 12 hpi. Fecal shedding of the virus started at 13 hpi and stopped at 23 hpi or
      at necropsy (4 dpi), respectively. Throughout the trial, none of the control
      calves tested positive for JV by ELISA or RT-PCR.

PMID- 21880761
TI  - Characterization of a canine homolog of human Aichivirus.
AB  - Many of our fatal "civilization" infectious diseases have arisen from
      domesticated animals. Although picornaviruses infect most mammals, infection of a
      companion animal is not known. Here we describe the identification and genomic
      characterization of the first canine picornavirus. Canine kobuvirus (CKoV),
      identified in stool samples from dogs with diarrhea, has a genomic organization
      typical of a picornavirus and encodes a 2,469-amino-acid polyprotein flanked by
      5' and 3' untranslated regions. Comparative phylogenetic analysis using various
      structural and nonstructural proteins of CKoV confirmed it as the animal virus
      homolog most closely related to human Aichivirus (AiV). Bayesian Markov chain
      Monte Carlo analysis suggests a mean recent divergence time of CKoV and AiV
      within the past 20 to 50 years, well after the domestication of canines. The
      discovery of CKoV provides new insights into the origin and evolution of AiV and
      the species specificity and pathogenesis of kobuviruses.

PMID- 21880762
TI  - Molecular characterization of the host defense activity of the barrier to
      autointegration factor against vaccinia virus.
AB  - The barrier to autointegration factor (BAF) is an essential cellular protein with
      functions in mitotic nuclear reassembly, retroviral preintegration complex
      stability, and transcriptional regulation. Molecular properties of BAF include
      the ability to bind double-stranded DNA in a sequence-independent manner,
      homodimerize, and bind proteins containing a LEM domain. These capabilities allow
      BAF to compact DNA and assemble higher-order nucleoprotein complexes, the nature
      of which is poorly understood. Recently, it was revealed that BAF also acts as a
      potent host defense against poxviral DNA replication in the cytoplasm. Here, we
      extend these observations by examining the molecular mechanism through which BAF
      acts as a host defense against vaccinia virus replication and cytoplasmic DNA in
      general. Interestingly, BAF rapidly relocalizes to transfected DNA from a variety
      of sources, demonstrating that BAF's activity as a host defense factor is not
      limited to poxviral infection. BAF's relocalization to cytoplasmic foreign DNA is
      highly dependent upon its DNA binding and dimerization properties but does not
      appear to require its LEM domain binding activity. However, the LEM domain
      protein emerin is recruited to cytoplasmic DNA in a BAF-dependent manner during
      both transfection and vaccinia virus infection. Finally, we demonstrate that the
      DNA binding and dimerization capabilities of BAF are essential for its function
      as an antipoxviral effector, while the presence of emerin is not required.
      Together, these data provide further mechanistic insight into which of BAF's
      molecular properties are employed by cells to impair the replication of
      poxviruses or respond to foreign DNA in general.

PMID- 21880763
TI  - Continuous CD8+ T-cell priming by dendritic cell cross-presentation of persistent
      antigen following adeno-associated virus-mediated gene delivery.
AB  - Recombinant adeno-associated virus (rAAV) vectors establish persistent transgene
      expression in the skeletal muscle of mice. How dendritic cells acquire encoded
      antigens for CD8(+) T-cell priming is unknown. Here we document CD8(+) T-cell
      priming after lethal irradiation and bone marrow reconstitution of mice treated
      with an AAV vector several weeks earlier. Temporal separation of vector delivery
      and successful class I antigen presentation indicated that T-cell priming does
      not necessarily require antigen synthesis in AAV-transduced dendritic cells. An
      apparent cross-presentation of antigen acquired from muscle suggests that
      strategies to limit transgene expression in dendritic cells will not prevent
      unwanted CD8(+) T-cell responses.

PMID- 21880764
TI  - Cross-reactive HIV-1-neutralizing human monoclonal antibodies identified from a
      patient with 2F5-like antibodies.
AB  - The genes encoding broadly HIV-1-neutralizing human monoclonal antibodies (MAbs)
      are highly divergent from their germ line counterparts. We have hypothesized that
      such high levels of somatic hypermutation could pose a challenge for elicitation
      of the broadly neutralizing (bn) Abs and that identification of less somatically
      mutated bn Abs may help in the design of effective vaccine immunogens. In a quest
      for such bn Abs, phage- and yeast-displayed antibody libraries, constructed using
      peripheral blood mononuclear cells (PBMCs) from a patient with bn serum
      containing Abs targeting the epitope of the bn MAb 2F5, were panned against
      peptides containing the 2F5 epitope and against the HIV-1 gp140(JR-FL). Two MAbs
      (m66 and m66.6) were identified; the more mutated variant (m66.6) exhibited
      higher HIV-1-neutralizing activity than m66, although it was weaker than 2F5 in a
      TZM-bl cell assay. Binding of both MAbs to gp41 alanine substitution mutant
      peptides required the DKW(664-666) core of the 2F5 epitope and two additional
      upstream residues (L(660,663)). The MAbs have long (21-residue) heavy-chain third
      complementarity-determining regions (CDR-H3s), and m66.6 (but not m66) exhibited
      polyspecific reactivity to self- and non-self-antigens. Both m66 and m66.6 are
      significantly less divergent from their germ line Ab counterparts than 2F5--they
      have a total of 11 and 18 amino acid changes, respectively, from the closest VH
      and Vkappa germ line gene products compared to 25 for 2F5. These new MAbs could
      help explore the complex maturation pathways involved in broad neutralization and
      its relationship with auto- and polyreactivity and may aid design of vaccine
      immunogens and development of therapeutics against HIV-1 infection.

PMID- 21880765
TI  - Genetic response to bacteriophage infection in Lactococcus lactis reveals a four
      strand approach involving induction of membrane stress proteins, D-alanylation of
      the cell wall, maintenance of proton motive force, and energy conservation.
AB  - In this study, whole-genome microarrays were used to gain insights into the
      global molecular response of Lactococcus lactis subsp. lactis IL1403 at an early
      stage of infection with the lytic phage c2. The bacterium differentially
      regulated the expression of 61 genes belonging to 14 functional categories,
      including cell envelope processes (12 genes), regulatory functions (11 genes),
      and carbohydrate metabolism (7 genes). The nature of these genes suggests a
      complex response involving four main mechanisms: (i) induction of membrane stress
      proteins, (ii) d-alanylation of cell wall lipoteichoic acids (LTAs), (iii)
      maintenance of the proton motive force (PMF), and (iv) energy conservation. The
      phage presence is sensed as a membrane stress in L. lactis subsp. lactis IL1403,
      which activated a cell wall-targeted response probably orchestrated by the
      concerted action of membrane phage shock protein C-like homologues, the global
      regulator SpxB, and the two-component system CesSR. The bacterium upregulated
      genes (ddl and dltABCD) responsible for incorporation of d-alanine esters into
      LTAs, an event associated with increased resistance to phage attack in Gram
      positive bacteria. The expression of genes (yshC, citE, citF) affecting both PMF
      components was also regulated to restore the physiological PMF, which was
      disrupted following phage infection. While mobilizing the response to the phage
      mediated stress, the bacterium activated an energy-saving program by repressing
      growth-related functions and switching to anaerobic respiration, probably to
      sustain the PMF and the overall cell response to phage. To our knowledge, this
      represents the first detailed description in L. lactis of the molecular
      mechanisms involved in the host response to the membrane perturbations mediated
      by phage infection.

PMID- 21880766
TI  - A mutation in UL15 of herpes simplex virus 1 that reduces packaging of cleaved
      genomes.
AB  - Herpesvirus genomic DNA is cleaved from concatemers that accumulate in infected
      cell nuclei. Genomic DNA is inserted into preassembled capsids through a unique
      portal vertex. Extensive analyses of viral mutants have indicated that intact
      capsids, the portal vertex, and all components of a tripartite terminase enzyme
      are required to both cleave and package viral DNA, suggesting that DNA cleavage
      and packaging are inextricably linked. Because the processes have not been
      functionally separable, it has been difficult to parse the roles of individual
      proteins in the DNA cleavage/packaging reaction. In the present study, a virus
      bearing the deletion of codons 400 to 420 of U(L)15, encoding a terminase
      component, was analyzed. This virus, designated vJB27, failed to replicate on
      noncomplementing cells but cleaved concatemeric DNA to ca. 35 to 98% of wild-type
      levels. No DNA cleavage was detected in cells infected with a U(L)15-null virus
      or a virus lacking U(L)15 codons 383 to 385, comprising a motif proposed to
      couple ATP hydrolysis to DNA translocation. The amount of vJB27 DNA protected
      from DNase I digestion was reduced compared to the wild-type virus by 6.5- to 200
      fold, depending on the DNA fragment analyzed, thus indicating a profound defect
      in DNA packaging. Capsids containing viral DNA were not detected in vJB27
      infected cells, as determined by electron microscopy. These data suggest that
      pU(L)15 plays an essential role in DNA translocation into the capsid and indicate
      that this function is separable from its role in DNA cleavage.

PMID- 21880767
TI  - Mechanism of glycyrrhizic acid inhibition of Kaposi's sarcoma-associated
      herpesvirus: disruption of CTCF-cohesin-mediated RNA polymerase II pausing and
      sister chromatid cohesion.
AB  - Glycyrrhizic acid (GA), a derivative of licorice, selectively inhibits the growth
      of lymphocytes latently infected with Kaposi's sarcoma-associated herpesvirus.
      The mechanism involves the deregulation of the multicistronic latency transcript,
      including the failure to generate the mature forms of viral mRNA encoding LANA.
      We show here that GA disrupts an RNA polymerase II (RNAPII) complex that
      accumulates at the CTCF-cohesin binding site within the first intron of the
      latency transcript. GA altered the enrichment of the RNAPII pausing complex,
      along with pausing factors SPT5 and NELF-A, at the intragenic CTCF-cohesin
      binding sites. GA blocked the interaction of cohesin subunit SMC3 with another
      cohesin subunit, RAD21, and reduced SPT5 interaction with RNAPII. Covalent
      coupling of GA to a solid support revealed that GA interacts with several
      cellular proteins, including SMC3 and SPT5, but not their respective interaction
      partners RAD21 and RNAPII. GA treatment also inhibited the transcription of some
      cellular genes, like c-myc, which contain a similar CTCF-cohesin binding site
      within the first intron. We also found that GA leads to a more general loss of
      sister chromatid cohesion for cellular chromosomes. These findings suggest that
      RNAPII pauses at intragenic CTCF-cohesin binding sites and that abrogation of
      this pausing by GA leads to loss of proper mRNA production and defects in sister
      chromatid cohesion, a process important for both viral and cellular chromosome
      stability.

PMID- 21880768
TI  - Human cytomegalovirus infection causes degradation of Sp100 proteins that
      suppress viral gene expression.
AB  - The interferon-inducible Sp100 proteins are thought to play roles in the
      chromatin pathway and in transcriptional regulation. Sp100A, the smallest
      isoform, is one of the major components of PML nuclear bodies (NBs) that exhibit
      intrinsic antiviral activity against several viruses. Since PML NBs are disrupted
      by the immediate-early 1 (IE1) protein during human cytomegalovirus (HCMV)
      infection, the modulation of Sp100 protein expression or activity during
      infection has been suggested. Here, we show that Sp100 proteins are lost largely
      in the late stages of HCMV infection. This event required viral gene expression
      and involved posttranscriptional control. The mutant virus with deletion of the
      sequence for IE1 (CR208) did not have Sp100 loss. In CR208 infection, PML
      depletion by RNA interference abrogated the accumulation of SUMO-modified Sp100A
      and of certain high-molecular-weight Sp100 isoforms but did not significantly
      affect unmodified Sp100A, suggesting that the IE1-induced disruption of PML NBs
      is not sufficient for the complete loss of Sp100 proteins. Sp100A loss was found
      to require proteasome activity. Depletion of all Sp100 proteins by RNA silencing
      enhanced HCMV replication and major IE (MIE) gene expression. Sp100 knockdown
      enhanced the acetylation level of histones associated with the MIE promoter,
      demonstrating that the repressive effect of Sp100 proteins may involve, at least
      in part, the epigenetic control of the MIE promoter. Sp100A was found to interact
      directly with IE1 through the N-terminal dimerization domain. These findings
      indicate that the IE1-dependent loss of Sp100 proteins during HCMV infection may
      represent an important requirement for efficient viral growth.

PMID- 21880769
TI  - Adaptive and innate transforming growth factor beta signaling impact herpes
      simplex virus 1 latency and reactivation.
AB  - Innate and adaptive immunity play important protective roles by combating herpes
      simplex virus 1 (HSV-1) infection. Transforming growth factor beta (TGF-beta) is
      a key negative cytokine regulator of both innate and adaptive immune responses.
      Yet, it is unknown whether TGF-beta signaling in either immune compartment
      impacts HSV-1 replication and latency. We undertook genetic approaches to address
      these issues by infecting two different dominant negative TGF-beta receptor type
      II transgenic mouse lines. These mice have specific TGF-beta signaling blockades
      in either T cells or innate cells. Mice were ocularly infected with HSV-1 to
      evaluate the effects of restricted innate or adaptive TGF-beta signaling during
      acute and latent infections. Limiting innate cell but not T cell TGF-beta
      signaling reduced virus replication in the eyes of infected mice. On the other
      hand, blocking TGF-beta signaling in either innate cells or T cells resulted in
      decreased latency in the trigeminal ganglia of infected mice. Furthermore,
      inhibiting TGF-beta signaling in T cells reduced cell lysis and leukocyte
      infiltration in corneas and trigeminal ganglia during primary HSV-1 infection of
      mice. These findings strongly suggest that TGF-beta signaling, which generally
      functions to dampen immune responses, results in increased HSV-1 latency.

PMID- 21880770
TI  - Direct sequencing and characterization of a clinical isolate of Epstein-Barr
      virus from nasopharyngeal carcinoma tissue by using next-generation sequencing
      technology.
AB  - Epstein-Barr virus (EBV)-encoded molecules have been detected in the tumor
      tissues of several cancers, including nasopharyngeal carcinoma (NPC), suggesting
      that EBV plays an important role in tumorigenesis. However, the nature of EBV
      with respect to genome width in vivo and whether EBV undergoes clonal expansion
      in the tumor tissues are still poorly understood. In this study, next-generation
      sequencing (NGS) was used to sequence DNA extracted directly from the tumor
      tissue of a patient with NPC. Apart from the human sequences, a clinically
      isolated EBV genome 164.7 kb in size was successfully assembled and named GD2
      (GenBank accession number HQ020558). Sequence and phylogenetic analyses showed
      that GD2 was closely related to GD1, a previously assembled variant derived from
      a patient with NPC. GD2 contains the most prevalent EBV variants reported in
      Cantonese patients with NPC, suggesting that it might be the prevalent strain in
      this population. Furthermore, GD2 could be grouped into a single subtype
      according to common classification criteria and contains only 6 heterozygous
      point mutations, suggesting the monoclonal expansion of GD2 in NPC. This study
      represents the first genome-wide analysis of a clinical isolate of EBV directly
      extracted from NPC tissue. Our study reveals that NGS allows the characterization
      of genome-wide variations of EBV in clinical tumors and provides evidence of
      monoclonal expansion of EBV in vivo. The pipeline could also be applied to the
      study of other pathogen-related malignancies. With additional NGS studies of NPC,
      it might be possible to uncover the potential causative EBV variant involved in
      NPC.

PMID- 21880772
TI  - Junin virus infects mouse cells and induces innate immune responses.
AB  - Junin virus is the causative agent for Argentine hemorrhagic fever, and its
      natural host is the New World rodent Calomys musculinus. The virus is transmitted
      to humans by aerosolization, and it is believed that many of the clinical
      symptoms are caused by cytokines produced by sentinel cells of the immune system.
      Here we used the Junin virus vaccine strain Candid 1 to determine whether mouse
      cells could be used to study virus entry and antiviral innate immune responses.
      We show that Candid 1 can infect and propagate in different mouse-derived cell
      lines through a low-pH-dependent, transferrin receptor 1-independent mechanism,
      suggesting that there is a second entry receptor. In addition, Candid 1 induced
      expression of the antiviral cytokines tumor necrosis factor alpha and beta
      interferon in macrophages, and this induction was independent of viral
      replication. Using Candid 1, as well as virus-like particles bearing the viral
      glycoprotein, to infect different primary cells and established macrophage cell
      lines with deletions in the Toll-like receptor (TLR) pathway, we show that TLR2
      is a cellular sensor of both the Parodi and Candid 1 viral glycoproteins. Because
      Junin virus is highly lethal in humans, the use of an experimentally tractable
      model system, such as the mouse, could provide a better understanding of the
      antiviral innate cellular responses to Junin virus and the role of these
      responses in pathogenesis.

PMID- 21880771
TI  - Increased frequency of regulatory T cells accompanies increased immune activation
      in rectal mucosae of HIV-positive noncontrollers.
AB  - Gut-associated lymphoid tissue (GALT) is a major site of HIV replication and
      CD4(+) T cell depletion. Furthermore, microbial translocation facilitated by
      mucosal damage likely contributes to the generalized immune activation observed
      in HIV infection. Regulatory T cells (Treg) help maintain homeostasis and
      suppress harmful immune activation during infection; however, in the case of
      persistent viral infections such as HIV, their role is less clear. Although a
      number of studies have examined Treg in blood during chronic infection, few have
      explored Treg in the gastrointestinal mucosa. For this study, paired blood and
      rectal biopsy samples were obtained from 12 HIV noncontrollers (viral load of
      >10,000 copies/ml plasma), 10 HIV controllers (viral load of <500 copies/ml
      plasma for more than 5 years), and 12 HIV seronegative control subjects.
      Noncontrollers had significantly higher percentages of Treg in rectal mononuclear
      cells (RMNC), but not in blood, compared to seronegative subjects (P = 0.001) or
      HIV controllers (P = 0.002). Mucosal Treg positively correlated with viral load
      (P = 0.01) and expression of immune activation markers by CD4(+) (P = 0.01) and
      CD8(+) (P = 0.07) T cells. Suppression assays indicated that mucosal and
      peripheral Treg of noncontrollers and controllers maintained their capacity to
      suppress non-Treg proliferation to a similar extent as Treg from seronegative
      subjects. Together, these findings reveal that rather than experiencing
      depletion, mucosal Treg frequency is enhanced during chronic HIV infection and is
      positively correlated with viral load and immune activation. Moreover, mucosal
      Treg maintain their suppressive ability during chronic HIV infection, potentially
      contributing to diminished HIV-specific T cell responses and viral persistence.

PMID- 21880773
TI  - Identification of the myelin oligodendrocyte glycoprotein as a cellular receptor
      for rubella virus.
AB  - Rubella virus (RV) is a highly transmissible pathogenic agent that causes the
      disease rubella. Maternal RV infection during early pregnancy causes the death of
      the fetus or congenital rubella syndrome in infants. However, the cellular
      receptor for RV has not yet been identified. In this study, we found that the
      myelin oligodendrocyte glycoprotein (MOG) specifically bound to the E1 envelope
      glycoprotein of RV, and an antibody against MOG could block RV infection. Most
      importantly, we also showed that ectopic expression of MOG on the cell surface of
      293T cells rendered this nonpermissive cell line permissive for RV entry and
      replication. Thus, this study has identified a cellular receptor for RV and
      suggests that blocking the MOG attachment site of RV may be a strategy for
      molecular intervention of RV infection.

PMID- 21880774
TI  - The latency-associated UL138 gene product of human cytomegalovirus sensitizes
      cells to tumor necrosis factor alpha (TNF-alpha) signaling by upregulating TNF
      alpha receptor 1 cell surface expression.
AB  - Many viruses antagonize tumor necrosis factor alpha (TNF-alpha) signaling in
      order to counteract its antiviral properties. One way viruses achieve this goal
      is to reduce TNF-alpha receptor 1 (TNFR1) on the surface of infected cells. Such
      a mechanism is also employed by human cytomegalovirus (HCMV), as recently
      reported by others and us. On the other hand, TNF-alpha has also been shown to
      foster reactivation of HCMV from latency. By characterizing a new variant of HCMV
      AD169, we show here that TNFR1 downregulation by HCMV only becomes apparent upon
      infection of cells with HCMV strains lacking the so-called ULb' region. This
      region contains genes involved in regulating viral immune escape, cell tropism,
      or latency and is typically lost from laboratory strains but present in low
      passage strains and clinical isolates. We further show that although ULb'
      positive viruses also contain the TNFR1-antagonizing function, this activity is
      masked by a dominant TNFR1 upregulation mediated by the ULb' gene product UL138.
      Isolated expression of UL138 in the absence of viral infection upregulates TNFR1
      surface expression and can rescue both TNFR1 reexpression and TNF-alpha
      responsiveness of cells infected with an HCMV mutant lacking the UL138-containing
      transcription unit. Given that the UL138 gene product is one of the few genes
      recognized to be expressed during HCMV latency and the known positive effects of
      TNF-alpha on viral reactivation, we suggest that via upregulating TNFR1 surface
      expression UL138 may sensitize latently infected cells to TNF-alpha-mediated
      reactivation of HCMV.

PMID- 21880775
TI  - Coxsackievirus A24 variant uses sialic acid-containing O-linked glycoconjugates
      as cellular receptors on human ocular cells.
AB  - Coxsackievirus A24 variant (CVA24v) is a main causative agent of acute
      hemorrhagic conjunctivitis (AHC), which is a highly contagious eye infection.
      Previously it has been suggested that CVA24v uses sialic acid-containing
      glycoconjugates as attachment receptors on corneal cells, but the nature of these
      receptors is poorly described. Here, we set out to characterize and identify the
      cellular components serving as receptors for CVA24v. Binding and infection
      experiments using corneal cells treated with deglycosylating enzymes or metabolic
      inhibitors of de novo glycosylation suggested that the receptor(s) used by CVA24v
      are constituted by sialylated O-linked glycans that are linked to one or more
      cell surface proteins but not to lipids. CVA24v bound better to mouse L929 cells
      overexpressing human P-selectin glycoprotein ligand-1 (PSGL-1) than to mock
      transfected cells, suggesting that PSGL-1 is a candidate receptor for CVA24v.
      Finally, binding competition experiments using a library of mono- and
      oligosaccharides mimicking known PSGL-1 glycans suggested that CVA24v binds to
      Neu5Acalpha2,3Gal disaccharides (Neu5Ac is N-acetylneuraminic acid). These
      results provide further insights into the early steps of the CVA24v life cycle.

PMID- 21880776
TI  - In silico reconstruction of viral genomes from small RNAs improves virus-derived
      small interfering RNA profiling.
AB  - RNA interference (RNAi) is the essential component of antiviral immunity in
      invertebrates and plants. One of the landmarks of the antiviral RNAi response is
      the production of virus-derived small interfering RNA (vsiRNA) from viral double
      stranded RNA (dsRNA). vsiRNAs constitute a fragmented image of the viral genome
      sequence that results from Dicer cleavage. vsiRNA sequence profiling is used
      extensively as a surrogate to study the antiviral RNAi response by determining
      the nature of the viral dsRNA molecules exposed to and processed by the RNAi
      machinery. The accuracy of these profiles depends on the actual viral genome
      sequence used as a reference to align vsiRNA reads, and the interpretation of
      inaccurate profiles can be misleading. Using Flock house virus and Drosophila
      melanogaster as a model RNAi-competent organism, we show accurate reconstruction
      of full-length virus reference sequence from vsiRNAs and prediction of the
      structure of defective interfering particles (DIs). We developed a Perl script,
      named Paparazzi, that reconstitutes viral genomes through an iterative
      alignment/consensus call procedure using a related reference sequence as
      scaffold. As prevalent DI-derived reads introduce artifacts during
      reconstruction, Paparazzi eliminates DI-specific reads to improve the quality of
      the reconstructed genome. Paparazzi constitutes a promising alternative to Sanger
      sequencing in this context and an effective tool to study antiviral RNAi
      mechanisms by accurately quantifying vsiRNA along the replicating viral genome.
      We further discuss Paparazzi as a companion tool for virus discovery as it
      provides full-length genome sequences and corrects for potential artifacts of
      assembly.

PMID- 21880777
TI  - A conserved peptide in West Nile virus NS4A protein contributes to proteolytic
      processing and is essential for replication.
AB  - The West Nile virus strain Kunjin virus (WNV(KUN)) NS4A protein is a
      multifunctional protein involved in membrane proliferation, stimulation of
      cellular pathways, and evasion of host defense and is a major component of the
      WNV(KUN) RNA replication complex. We identified a highly conserved region ((120)P
      E-P-E(123)) upstream of the viral protease dibasic cleavage site and investigated
      whether this motif was required for WNV(KUN) replication. Single point mutations
      to alanine and a PEPE deletion mutation were created in a full-length infectious
      WNV(KUN) molecular clone. All mutations drastically impaired viral replication
      and virion production, except that of the P122A mutant, which was slightly
      attenuated. These mutations were subsequently transferred to a WNV(KUN) replicon
      to specifically assess effects on RNA replication alone. Again, all mutants,
      except P122A, showed severely reduced negative-sense RNA production as well as
      decreased viral protein production. Correspondingly, immunofluorescence analyses
      showed a lack of double-stranded RNA (dsRNA) labeling and a dispersed
      localization of the WNV(KUN) proteins, suggesting that replication complex
      formation was additionally impaired. Attempts to rescue replication via
      conservative mutants largely failed except for substitution of Asp at E121,
      suggesting that a negative charge at this residue is equally important. Analysis
      of viral protein processing suggested that cleavage of the 2K peptide from NS4A
      did not occur with the mutant constructs. These observations imply that the
      combined effects of proline and negatively charged residues within the PEPE
      peptide are essential to promote the cleavage of 2K from NS4A, which is a
      prerequisite for efficient WNV replication.

PMID- 21880778
TI  - Efficient cross-species capture hybridization and next-generation sequencing of
      mitochondrial genomes from noninvasively sampled museum specimens.
AB  - The ability to uncover the phylogenetic history of recently extinct species and
      other species known only from archived museum material has rapidly improved due
      to the reduced cost and increased sequence capacity of next-generation sequencing
      technologies. One limitation of these approaches is the difficulty of isolating
      and sequencing large, orthologous DNA regions across multiple divergent species,
      which is exacerbated for museum specimens, where DNA quality varies greatly
      between samples and contamination levels are often high. Here we describe the use
      of cross-species DNA capture hybridization techniques and next-generation
      sequencing to selectively isolate and sequence partial to full-length
      mitochondrial DNA genomes from the degraded DNA of museum specimens, using probes
      generated from the DNA of a single extant species. We demonstrate our approach on
      specimens from an enigmatic gliding mammal, the Sunda colugo, which is widely
      distributed throughout Southeast Asia. We isolated DNA from 13 colugo specimens
      collected 47-170 years ago, and successfully captured and sequenced mitochondrial
      DNA from every specimen, frequently recovering fragments with 10%-13% sequence
      divergence from the capture probe sequence. Phylogenetic results reveal deep
      genetic divergence among colugos, both within and between the islands of Borneo
      and Java, as well as between the Malay Peninsula and different Sundaic islands.
      Our method is based on noninvasive sampling of minute amounts of soft tissue
      material from museum specimens, leaving the original specimen essentially
      undamaged. This approach represents a paradigm shift away from standard PCR-based
      approaches for accessing population genetic and phylogenomic information from
      poorly known and difficult-to-study species.

PMID- 21880779
TI  - The human gut virome: inter-individual variation and dynamic response to diet.
AB  - Immense populations of viruses are present in the human gut and other body sites.
      Understanding the role of these populations (the human "virome") in health and
      disease requires a much deeper understanding of their composition and dynamics in
      the face of environmental perturbation. Here, we investigate viromes from human
      subjects on a controlled feeding regimen. Longitudinal fecal samples were
      analyzed by metagenomic sequencing of DNA from virus-like particles (VLP) and
      total microbial communities. Assembly of 336 Mb of VLP sequence yielded 7175
      contigs, many identifiable as complete or partial bacteriophage genomes. Contigs
      were rich in viral functions required in lytic and lysogenic growth, as well as
      unexpected functions such as viral CRISPR arrays and genes for antibiotic
      resistance. The largest source of variance among virome samples was interpersonal
      variation. Parallel deep-sequencing analysis of bacterial populations showed
      covaration of the virome with the larger microbiome. The dietary intervention was
      associated with a change in the virome community to a new state, in which
      individuals on the same diet converged. Thus these data provide an overview of
      the composition of the human gut virome and associate virome structure with diet.

PMID- 21880780
TI  - The presence of multiple introns is essential for ERECTA expression in
      Arabidopsis.
AB  - Gene expression in eukaryotes is often enhanced by the presence of introns.
      Depending on the specific gene, this enhancement can be minor or very large and
      occurs at both the transcriptional and post-transcriptional levels. The
      Arabidopsis ERECTA gene contains 27 exons encoding a receptor-like kinase that
      promotes cell proliferation and inhibits cell differentiation in above-ground
      plant organs. The expression of ERECTA very strongly depends on the presence of
      introns. The intronless ERECTA gene does not rescue the phenotype of erecta
      mutant plants and produces about 500-900 times less protein compared with the
      identical construct containing introns. This result is somewhat surprising as the
      region upstream of the ERECTA coding sequence effectively promotes the expression
      of extraneous genes. Here, we demonstrate that introns are essential for ERECTA
      mRNA accumulation and, to a lesser extent, for mRNA utilization in translation.
      Since mRNA produced by intronless ERECTA is degraded at the 3' end, we speculate
      that introns increase mRNA accumulation through increasing its stability at least
      in part. No individual intron is absolutely necessary for ERECTA expression, but
      rather multiple introns in specific locations increase ERECTA expression in an
      additive manner. The ability of introns to promote ERECTA expression might be
      linked to the process of splicing and not to a particular intron sequence.

PMID- 21880781
TI  - ApoE is required for maintenance of the dentate gyrus neural progenitor pool.
AB  - Many genes regulating adult neurogenesis have been identified and are known to
      play similar roles during early neuronal development. We recently identified
      apolipoprotein E (ApoE) as a gene the expression of which is essentially absent
      in early brain progenitors but becomes markedly upregulated in adult dentate
      gyrus stem/progenitor cells. Here, we demonstrate that ApoE deficiency impairs
      adult dentate gyrus development by affecting the neural progenitor pool over
      time. We utilized ApoE-deficient mice crossed to a nestin-GFP reporter to
      demonstrate that dentate gyrus progenitor cells proliferate more rapidly at early
      ages, which is subsequently accompanied by an overall decrease in neural
      progenitor cell number at later time points. This appears to be secondary to over
      proliferation early in life and ultimate depletion of the Type 1 nestin- and GFAP
      expressing neural stem cells. We also rescue the proliferation phenotype with an
      ApoE-expressing retrovirus, demonstrating that ApoE works directly in this
      regard. These data provide novel insight into late hippocampal development and
      suggest a possible role for ApoE in neurodegenerative diseases.

PMID- 21880782
TI  - Cell dynamics in fetal intestinal epithelium: implications for intestinal growth
      and morphogenesis.
AB  - The cellular mechanisms that drive growth and remodeling of the early intestinal
      epithelium are poorly understood. Current dogma suggests that the murine fetal
      intestinal epithelium is stratified, that villi are formed by an epithelial
      remodeling process involving the de novo formation of apical surface at secondary
      lumina, and that radial intercalation of the stratified cells constitutes a major
      intestinal lengthening mechanism. Here, we investigate cell polarity, cell cycle
      dynamics and cell shape in the fetal murine intestine between E12.5 and E14.5. We
      show that, contrary to previous assumptions, this epithelium is pseudostratified.
      Furthermore, epithelial nuclei exhibit interkinetic nuclear migration, a process
      wherein nuclei move in concert with the cell cycle, from the basal side (where
      DNA is synthesized) to the apical surface (where mitosis takes place); such
      nuclear movements were previously misinterpreted as the radial intercalation of
      cells. We further demonstrate that growth of epithelial girth between E12.5 and
      E14.5 is driven by microtubule- and actinomyosin-dependent apicobasal elongation,
      rather than by progressive epithelial stratification as was previously thought.
      Finally, we show that the actin-binding protein Shroom3 is crucial for the
      maintenance of the single-layered pseudostratified epithelium. In mice lacking
      Shroom3, the epithelium is disorganized and temporarily stratified during villus
      emergence. These results favor an alternative model of intestinal morphogenesis
      in which the epithelium remains single layered and apicobasally polarized
      throughout early intestinal development.

PMID- 21880783
TI  - Prdm1a and miR-499 act sequentially to restrict Sox6 activity to the fast-twitch
      muscle lineage in the zebrafish embryo.
AB  - Sox6 has been proposed to play a conserved role in vertebrate skeletal muscle
      fibre type specification. In zebrafish, sox6 transcription is repressed in slow
      twitch progenitors by the Prdm1a transcription factor. Here we identify sox6 cis
      regulatory sequences that drive fast-twitch-specific expression in a Prdm1a
      dependent manner. We show that sox6 transcription subsequently becomes
      derepressed in slow-twitch fibres, whereas Sox6 protein remains restricted to
      fast-twitch fibres. We find that translational repression of sox6 is mediated by
      miR-499, the slow-twitch-specific expression of which is in turn controlled by
      Prdm1a, forming a regulatory loop that initiates and maintains the slow-twitch
      muscle lineage.

PMID- 21880784
TI  - Temporally controlled modulation of FGF/ERK signaling directs midbrain
      dopaminergic neural progenitor fate in mouse and human pluripotent stem cells.
AB  - Effective induction of midbrain-specific dopamine (mDA) neurons from stem cells
      is fundamental for realizing their potential in biomedical applications relevant
      to Parkinson's disease. During early development, the Otx2-positive neural
      tissues are patterned anterior-posteriorly to form the forebrain and midbrain
      under the influence of extracellular signaling such as FGF and Wnt. In the
      mesencephalon, sonic hedgehog (Shh) specifies a ventral progenitor fate in the
      floor plate region that later gives rise to mDA neurons. In this study, we
      systematically investigated the temporal actions of FGF signaling in mDA neuron
      fate specification of mouse and human pluripotent stem cells and mouse induced
      pluripotent stem cells. We show that a brief blockade of FGF signaling on exit of
      the lineage-primed epiblast pluripotent state initiates an early induction of
      Lmx1a and Foxa2 in nascent neural progenitors. In addition to inducing ventral
      midbrain characteristics, the FGF signaling blockade during neural induction also
      directs a midbrain fate in the anterior-posterior axis by suppressing
      caudalization as well as forebrain induction, leading to the maintenance of
      midbrain Otx2. Following a period of endogenous FGF signaling, subsequent
      enhancement of FGF signaling by Fgf8, in combination with Shh, promotes mDA
      neurogenesis and restricts alternative fates. Thus, a stepwise control of FGF
      signaling during distinct stages of stem cell neural fate conversion is crucial
      for reliable and highly efficient production of functional, authentic midbrain
      specific dopaminergic neurons. Importantly, we provide evidence that this novel,
      small-molecule-based strategy applies to both mouse and human pluripotent stem
      cells.

PMID- 21880785
TI  - UNC-6/netrin and its receptors UNC-5 and UNC-40/DCC modulate growth cone
      protrusion in vivo in C. elegans.
AB  - The UNC-6/netrin guidance cue functions in axon guidance in vertebrates and
      invertebrates, mediating attraction via UNC-40/DCC family receptors and repulsion
      via by UNC-5 family receptors. The growth cone reads guidance cues and extends
      lamellipodia and filopodia, actin-based structures that sense the extracellular
      environment and power the forward motion of the growth cone. We show that UNC
      6/netrin, UNC-5 and UNC-40/DCC modulated the extent of growth cone protrusion
      that correlated with attraction versus repulsion. Loss-of-function unc-5 mutants
      displayed increased protrusion in repelled growth cones, whereas loss-of-function
      unc-6 or unc-40 mutants caused decreased protrusion. In contrast to previous
      studies, our work suggests that the severe guidance defects in unc-5 mutants may
      be due to latent UNC-40 attractive signaling that steers the growth cone back
      towards the ventral source of UNC-6. UNC-6/Netrin signaling also controlled
      polarity of growth cone protrusion and F-actin accumulation that correlated with
      attraction versus repulsion. However, filopodial dynamics were affected
      independently of polarity of protrusion, indicating that the extent versus
      polarity of protrusion are at least in part separate mechanisms. In summary, we
      show here that growth cone guidance in response to UNC-6/netrin involves a
      combination of polarized growth cone protrusion as well as a balance between
      stimulation and inhibition of growth cone (e.g. filopodial) protrusion.

PMID- 21880786
TI  - Integrin-dependent and -independent functions of astrocytic fibronectin in
      retinal angiogenesis.
AB  - Fibronectin (FN) is a major component of the extracellular matrix and functions
      in cell adhesion, cell spreading and cell migration. In the retina, FN is
      transiently expressed and assembled on astrocytes (ACs), which guide sprouting
      tip cells and deposit a provisional matrix for sprouting angiogenesis. The
      precise function of FN in retinal angiogenesis is largely unknown. Using genetic
      tools, we show that astrocytes are the major source of cellular FN during
      angiogenesis in the mouse retina. Deletion of astrocytic FN reduces radial
      endothelial migration during vascular plexus formation in a gene dose-dependent
      manner. This effect correlates with reduced VEGF receptor 2 and PI3K/AKT
      signalling, and can be mimicked by selectively inhibiting VEGF-A binding to FN
      through intraocular injection of blocking peptides. By contrast, AC-specific
      replacement of the integrin-binding RGD sequence with FN-RGE or endothelial
      deletion of itga5 shows little effect on migration and PI3K/AKT signalling, but
      impairs filopodial alignment along AC processes, suggesting that FN-integrin
      alpha5beta1 interaction is involved in filopodial adhesion to the astrocytic
      matrix. AC FN shares its VEGF-binding function and cell-surface distribution with
      heparan-sulfate (HS), and genetic deletion of both FN and HS together greatly
      enhances the migration defect, indicating a synergistic function of FN and HS in
      VEGF binding. We propose that in vivo the VEGF-binding properties of FN and HS
      promote directional tip cell migration, whereas FN integrin-binding functions to
      support filopodia adhesion to the astrocytic migration template.

PMID- 21880787
TI  - Individual axons regulate the myelinating potential of single oligodendrocytes in
      vivo.
AB  - The majority of axons in the central nervous system (CNS) are eventually
      myelinated by oligodendrocytes, but whether the timing and extent of myelination
      in vivo reflect intrinsic properties of oligodendrocytes, or are regulated by
      axons, remains undetermined. Here, we use zebrafish to study CNS myelination at
      single-cell resolution in vivo. We show that the large caliber Mauthner axon is
      the first to be myelinated (shortly before axons of smaller caliber) and that the
      presence of supernumerary large caliber Mauthner axons can profoundly affect
      myelination by single oligodendrocytes. Oligodendrocytes that typically myelinate
      just one Mauthner axon in wild type can myelinate multiple supernumerary Mauthner
      axons. Furthermore, oligodendrocytes that exclusively myelinate numerous smaller
      caliber axons in wild type can readily myelinate small caliber axons in addition
      to the much larger caliber supernumerary Mauthner axons. These data indicate that
      single oligodendrocytes can myelinate diverse axons and that their myelinating
      potential is actively regulated by individual axons.

PMID- 21880788
TI  - Aflibercept (VEGF Trap) in inoperable stage III or stage iv melanoma of cutaneous
      or uveal origin.
AB  - PURPOSE: Aflibercept is a soluble decoy VEGF receptor and angiogenesis inhibitor
      with potent preclinical antitumor activity in melanoma. We conducted a
      multicenter phase II study in patients with inoperable stage III or IV melanoma
      and no prior chemotherapy. EXPERIMENTAL DESIGN: A two-stage design was adopted to
      evaluate 4-month progression-free survival rate (PFSR) and response rate.
      Aflibercept was given at 4 mg/kg intravenously every 2 weeks. Response was
      assessed every 8 weeks. First-stage accrual of 21 patients was specified and with
      an adequate 4-month PFSR accrual continued to a total of 41. RESULTS: Forty-one
      patients of ages 23 to 84 (median = 57) were enrolled. Thirty-nine had American
      Joint Committee on Cancer stage IV (5 M1a, 7 M1b, and 27 M1c) and 2 had
      inoperable stage IIIC (N3). Eastern Cooperative Oncology Group (ECOG) performance
      status was 0 (27 patients) or 1 (14 patients). Ten patients had primary uveal
      melanoma, 28 cutaneous, and 3 had unknown primaries. A median of 7 cycles were
      initiated (range: 1-56). Grade 3 and 4 toxicities included hypertension in 9
      patients (22%) and proteinuria in 6 (15%). Among 40 patients evaluable for
      efficacy (those who initiated aflibercept), 3 (7.5%) had a confirmed partial
      response and 20 had progression-free survival of 4 months or above. The predicted
      1-year survival rate derived from the Korn meta-analysis model is 36% (N = 39),
      whereas we observed a corresponding 56.4% survival rate at 1 year (95% CI, 43-74,
      P < 0.005). Median overall survival in this trial is 16.3 months (95% CI, 9.2 to
      not reached). We observed a significant association between severity of
      hypertension following aflibercept and survival improvement. CONCLUSIONS:
      Aflibercept showed promising activity in patients with metastatic melanoma of
      cutaneous or uveal origin. Further evaluation of aflibercept as a single agent
      and in combination is warranted.

PMID- 21880789
TI  - Comparison of continuous versus categorical tumor measurement-based metrics to
      predict overall survival in cancer treatment trials.
AB  - PURPOSE: The categorical definition of response assessed via the Response
      Evaluation Criteria in Solid Tumors has documented limitations. We sought to
      identify alternative metrics for tumor response that improve prediction of
      overall survival. EXPERIMENTAL DESIGN: Individual patient data from three North
      Central Cancer Treatment Group trials (N0026, n = 117; N9741, n = 1,109; and
      N9841, n = 332) were used. Continuous metrics of tumor size based on longitudinal
      tumor measurements were considered in addition to a trichotomized response
      [TriTR: response (complete or partial) vs. stable disease vs. progression). Cox
      proportional hazards models, adjusted for treatment arm and baseline tumor
      burden, were used to assess the impact of the metrics on subsequent overall
      survival, using a landmark analysis approach at 12, 16, and 24 weeks
      postbaseline. Model discrimination was evaluated by the concordance (c) index.
      RESULTS: The overall best response rates for the three trials were 26%, 45%, and
      25%, respectively. Although nearly all metrics were statistically significantly
      associated with overall survival at the different landmark time points, the
      concordance indices (c-index) for the traditional response metrics ranged from
      0.59 to 0.65; for the continuous metrics from 0.60 to 0.66; and for the TriTR
      metrics from 0.64 to 0.69. The c-indices for TriTR at 12 weeks were comparable
      with those at 16 and 24 weeks. CONCLUSIONS: Continuous tumor measurement-based
      metrics provided no predictive improvement over traditional response-based
      metrics or TriTR; TriTR had better predictive ability than best TriTR or
      confirmed response. If confirmed, TriTR represents a promising endpoint for
      future phase II trials.

PMID- 21880790
TI  - EGFR- and VEGF(R)-targeted small molecules show synergistic activity in
      colorectal cancer models refractory to combinations of monoclonal antibodies.
AB  - PURPOSE: Epidermal growth factor receptor (EGFR) and VEGF(R) signaling show
      extensive cross-talk, providing a rationale for joint targeting of the two
      pathways. However, combinations of monoclonal antibodies (mAb) targeting EGFR and
      VEGF showed disappointing activity in patients with colorectal cancer (CRC). We
      speculated that inhibition of surface receptors and ligands might only partly
      prevent oncogenic signaling whereas small-molecule tyrosine kinase inhibitors
      (TKI) would also influence intracellular signaling. EXPERIMENTAL DESIGN: Mice
      with CRC xenografts were treated with two TKIs, vargatef and afatinib, or with
      two mAbs, bevacizumab and cetuximab, and their influence on tumor growth,
      viability, in vivo DNA synthesis, and the presence of phosphorylated EGFR and
      VEGFR was determined. The activity of the TKIs was further characterized in CRC
      cells with different KRAS status. RESULTS: Vargatef and afatinib together showed
      strong tumor growth inhibition toward HT-29 xenografts compared with either drug
      alone, which was associated with a 5-fold increase in apoptotic tumor cell death.
      In comparison, bevacizumab and cetuximab together were exclusively cytostatic
      with no more activity than either drug alone. Exposure to the two TKIs was
      accompanied by a marked decrease of tumor-associated intracellular phospho-VEGFR1
      and phospho-EGFR, whereas similar exposure to the two mAbs had no detectable
      effect. A synergistic activity of vargatef plus afatinib was observed in all
      eight CRC cell lines examined, independent of KRAS status. CONCLUSIONS: Our
      results indicate that attenuation of intracellular EGFR and/or VEGF signaling is
      required for cytotoxic activity. These findings provide a rationale for trials of
      the TKIs, even in patients with mutant KRAS.

PMID- 21880791
TI  - Novel insights into the role of interleukin-27 and interleukin-23 in human
      malignant and normal plasma cells.
AB  - Multiple myeloma is a monoclonal postgerminal center tumor that has phenotypic
      features of plasmablasts and/or plasma cells and usually localizes at multiple
      sites in the bone marrow. The pathogenesis of multiple myeloma is complex and
      dependent on the interactions between tumor cells and their microenvironment.
      Different cytokines, chemokines, and proangiogenic factors released in the tumor
      microenvironment are known to promote multiple myeloma cell growth. Here, we
      report recent advances on the role of 2 strictly related immunomodulatory
      cytokines, interleukin-27 (IL-27) and IL-23, in human normal and neoplastic
      plasma cells, highlighting their ability to (i) act directly against multiple
      myeloma cells, (ii) influence the multiple myeloma microenvironment by targeting
      osteoclast and osteoblast cells, and (iii) modulate normal plasma cell function.
      Finally, the therapeutic implication of these studies is discussed.

PMID- 21880793
TI  - Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic
      rickets and healthy humans.
AB  - CONTEXT: In autosomal dominant hypophosphatemic rickets (ADHR), fibroblast growth
      factor 23 (FGF23) resists cleavage, causing increased plasma FGF23 levels. The
      clinical phenotype includes variable onset during childhood or adulthood and
      waxing/waning of hypophosphatemia. Delayed onset after puberty in females
      suggests iron status may be important. OBJECTIVE: Studies were performed to test
      the hypothesis that plasma C-terminal and intact FGF23 concentrations are related
      to serum iron concentrations in ADHR. DESIGN AND SETTING: Cross-sectional and
      longitudinal studies of ADHR and a cross-sectional study in healthy subjects were
      conducted at an academic medical center. PARTICIPANTS: Participants included 37
      subjects with ADHR mutations from four kindreds and 158 healthy adult controls.
      MAIN OUTCOME MEASURE: The relationships of serum iron concentrations with plasma
      C-terminal and intact FGF23 concentrations were evaluated. RESULTS: Serum
      phosphate and 1,25-dihydroxyvitamin D correlated negatively with C-terminal FGF23
      and intact FGF23 in ADHR but not in controls. Serum iron was negatively
      correlated to both C-terminal FGF23 (r = -0.386; P < 0.05) and intact FGF23 (r = 
      0.602; P < 0.0001) in ADHR. However, control subjects also demonstrated a
      negative relationship of serum iron with C-terminal FGF23 (r = -0.276; P < 0.001)
      but no relationship with intact FGF23. Longitudinally in ADHR subjects, C
      terminal FGF23 and intact FGF23 concentrations changed negatively with iron
      concentrations (P < 0.001 and P = 0.055, respectively), serum phosphate changed
      negatively with C-terminal FGF23 and intact FGF23 (P < 0.001), and there was a
      positive relationship between serum iron and phosphate (P < 0.001). CONCLUSIONS:
      Low serum iron is associated with elevated FGF23 in ADHR. However, in controls,
      low serum iron was also associated with elevated C-terminal FGF23, but not intact
      FGF23, suggesting cleavage maintains homeostasis despite increased FGF23
      expression.

PMID- 21880792
TI  - Evaluation of CYP2D6 and efficacy of tamoxifen and raloxifene in women treated
      for breast cancer chemoprevention: results from the NSABP P1 and P2 clinical
      trials.
AB  - BACKGROUND: Controversy exists regarding the association between CYP2D6 enzyme
      activity and tamoxifen effectiveness in the adjuvant treatment of invasive breast
      cancer; however, this association in the primary prevention of breast cancer is
      unknown. METHODS: We conducted a nested case-control study in the context of the
      NSABP P1 and P2 prevention trials to determine the impact of CYP2D6 genotype,
      CYP2D6 inhibitor use, and metabolizer status (CYP2D6 genotype combined with
      CYP2D6 inhibitor use), on breast cancer events. Women who developed breast cancer
      (both noninvasive and invasive) while on 5 years of selective estrogen receptor
      modulators therapy (cases) were matched to controls free of breast cancer.
      Comprehensive CYP2D6 genotyping was conducted for alleles associated with absent
      (*3, *4, *5, and *6), reduced (*10, *17, and *41), and increased (*1XN and *2XN)
      enzyme activity. Information regarding the use of CYP2D6 inhibitors was recorded.
      RESULTS: A total of 591 cases were matched to 1,126 controls and DNA was
      genotyped in more than 97%. In patients treated with tamoxifen, there was no
      association of CYP2D6 genotype [OR (extensive/poor metabolizer): 0.90; 95% CI:
      0.46-1.74, P = 0.74), use of a potent CYP2D6 inhibitor (OR 0.92; 95% CI: 0.575
      1.486), or CYP2D6 metabolizer status (OR 1.03; 95% CI: 0.669-1.607) with breast
      cancer occurrence. Likewise, there was no association between any CYP2D6
      metabolism parameter with breast cancer events in raloxifene-treated patients.
      CONCLUSION: In the NSABP P1 and P2 clinical trials, alterations in CYP2D6
      metabolism are not associated with either tamoxifen or raloxifene efficacy.

PMID- 21880794
TI  - Type 1 hyperlipoproteinemia and recurrent acute pancreatitis due to lipoprotein
      lipase antibody in a young girl with Sjogren's syndrome.
AB  - CONTEXT: Type 1 hyperlipoproteinemia (T1HLP) in childhood is most often due to
      genetic deficiency of lipoprotein lipase (LPL) or other related proteins.
      OBJECTIVE: The aim was to report a case of marked hypertriglyceridemia and
      recurrent acute pancreatitis due to the presence of LPL autoantibody in a young
      girl who was subsequently diagnosed with Sjogren's syndrome. SUBJECT AND METHODS:
      A 9-yr-old African-American girl presented with acute pancreatitis and serum
      triglycerides of 4784 mg/dl. Strict restriction of dietary fat reduced serum
      triglycerides, but she continued to experience recurrent pancreatitis.
      Approximately 18 months thereafter, she developed transient pauciarticular
      arthritis with elevated serum antinuclear antibody (>1:1280). Minor salivary
      gland biopsy revealed chronic sialadenitis with a dense periductal lymphocytic
      aggregate suggestive of Sjogren's syndrome. Genomic DNA was analyzed for LPL,
      GPIHBP1, APOA5, APOC2, and LMF1. Immunoblotting was performed to detect serum LPL
      autoantibody. RESULTS: The patient had no disease-causing variants in LPL,
      GPIHBP1, APOA5, APOC2, or LMF1. Immunoblotting revealed serum LPL antibody. The
      patient responded to immunosuppressive therapy for Sjogren's syndrome with
      resolution of hypertriglyceridemia. CONCLUSIONS: Unexplained T1HLP in childhood
      could be secondary to LPL deficiency induced by autoantibodies. Therefore,
      diagnosis of autoimmune T1HLP should be entertained if clinical features are
      suggestive of an autoimmune process.

PMID- 21880795
TI  - Preoperative insulin resistance and the impact of feeding on postoperative
      protein balance: a stable isotope study.
AB  - CONTEXT: Major surgery induces a catabolic state resulting in a net loss of body
      protein. OBJECTIVES: Our objective was to compare protein metabolism before and
      after surgery in nondiabetic patients with and without preoperative insulin
      resistance (IR). It was hypothesized that the anabolic response to feeding would
      be significantly impaired in those patients with preoperative insulin resistance.
      DESIGN: A hyperinsulinemic-euglycemic clamp has been used to identify two groups
      of patients: IR and insulin sensitive (IS). A tracer kinetics technique has been
      used to evaluate the metabolic response to food intake in both groups. SETTING:
      Patients undergoing cardiopulmonary bypass participated. PATIENTS OR OTHER
      PARTICIPANTS: Ten IS patients and 10 IR patients were enrolled in the study.
      INTERVENTION: After an overnight fasting, a 3-h infusion of a solution composed
      of 20% glucose and of amino acids at a rate of 0.67 and 0.44 kcal/kg . h,
      respectively, was started in each group. Phenylalanine kinetics were studied at
      the end of fasting and feeding. MAIN OUTCOME MEASURE: Effect of feeding on
      protein balance before and after surgery was evaluated. Protein balance has been
      measured as the net difference of protein breakdown minus protein synthesis.
      RESULTS: Protein balance increase after postoperative feeding was blunted only in
      the IR group. In contrast, in the IS group, the postoperative anabolic effect of
      feeding was the same as before surgery. CONCLUSIONS: These findings propose a
      link between insulin resistance and protein metabolism. When non-IR patients are
      fed, a significant anabolic effect in the postoperative period is demonstrated.
      In contrast, IR patients are less able to use feeding for synthetic purposes.

PMID- 21880796
TI  - A novel entity of clinically isolated adrenal insufficiency caused by a partially
      inactivating mutation of the gene encoding for P450 side chain cleavage enzyme
      (CYP11A1).
AB  - CONTEXT: Cytochrome P450 side-chain cleavage enzyme (CYP11A1) facilitates the
      first and rate-limiting step of steroidogenesis. Only nine patients with CYP11A1
      deficiency have been described. All patients presented with adrenal insufficiency
      (AI) and disorder of sex development in 46,XY individuals. OBJECTIVE: Our
      objective was to define the pathogenic consequences of a novel CYP11A1 mutation
      (p.R451W) found in two brothers with isolated adrenal insufficiency. PATIENTS:
      The two brothers (46,XY) presented with AI and normal male genital development.
      The older boy first presented with signs and symptoms suggestive of AI at the age
      of 2.8 yr but was only diagnosed at the age of 4.1 yr during an adrenal crisis.
      The younger brother was diagnosed with AI at the age of 2.5 yr while being
      clinically asymptomatic. Both boys had entirely normal appearance of their
      external genitalia. RESULTS: The novel p.R451W mutation and five published
      missense CYP11A1 mutations were characterized employing two in vitro approaches
      using the natural substrate cholesterol and the intermediate 22R
      hydroxycholesterol, respectively. Pregnenolone generation was measured by highly
      specific liquid chromatography tandem mass spectrometry. p.R451W had 30% of wild
      type activity consistent with the clinical phenotype in our patients. Two
      previously published mutations (p.L222P and p.A359V) had 2- to 3-fold higher in
      vitro activities than originally reported, correlating better with the associated
      phenotypes. CONCLUSIONS: We provide the first evidence that partial CYP11A1
      deficiency has to be considered as a differential diagnosis in clinically
      isolated adrenal insufficiency. Our assays demonstrate a tighter genotype
      phenotype correlation in CYP11A1 deficiency than previous in vitro studies.

PMID- 21880797
TI  - Associations of salivary cortisol levels with metabolic syndrome and its
      components: the multi-ethnic study of atherosclerosis.
AB  - CONTEXT: Prior research has identified associations between social-environmental
      factors and metabolic syndrome (MetS) components. The physiological mechanisms
      underlying these associations are not fully understood, but alterations in
      activity of the hypothalamic-pituitary-adrenal axis, a stress-responsive
      biological system, have been hypothesized to play a role. OBJECTIVE: The aim of
      the study was to determine whether MetS diagnosis and specific clusters of MetS
      components (waist circumference, high-density lipoproteins, glucose, and blood
      pressure) are associated with cortisol levels. DESIGN AND SETTING: We conducted
      cross-sectional analyses of data from the Multi-Ethnic Study of Atherosclerosis
      (MESA) study in the general community. PATIENTS OR OTHER PARTICIPANTS: We studied
      a population-based sample of 726 adults (ages 48 to 89 yr) who do not have
      clinical diabetes. INTERVENTION(S): There were no interventions. MAIN OUTCOME
      MEASURE(S): Cortisol awakening response, cortisol decline across the waking day,
      and total cortisol output were analyzed (using 18 timed measures of salivary
      cortisol over 3 d). RESULTS: Overall, we found little evidence that the presence
      of MetS or its components is related to cortisol output or patterns. Contrary to
      expectation, the presence of MetS was associated with lower rather than higher
      area under the curve, and no consistent pattern was observed when MetS components
      or subsets of components were examined in relation to cortisol. CONCLUSIONS: Our
      findings do not support the hypothesis that differences in level or diurnal
      pattern of salivary cortisol output are associated with MetS among persons
      without clinical diabetes.

PMID- 21880798
TI  - Neuropilin-2 expression in papillary thyroid carcinoma: correlation with VEGF-D
      expression, lymph node metastasis, and VEGF-D-induced aggressive cancer cell
      phenotype.
AB  - CONTEXT: Neuropilin-2 (Nrp2) is a coreceptor for vascular endothelial growth
      factor-D (VEGF-D) that is expressed on the surface of endothelial cells.
      Recently, Nrp2 was shown to play a role in lymph node metastasis and promotion of
      cancer cell migration. VEGF-D also promotes lymphangiogenesis, which in turn
      promotes tumor metastasis. OBJECTIVE: The aim was to study the role of neuropilin
      2 in lymph node metastasis in human papillary thyroid carcinoma (PTC). DESIGN:
      Expression of Nrp2 was studied by immunohistochemistry and the relationship
      between Nrp2 expression and lymph node metastasis, VEGF-D expression and other
      established clinicopathological variables were analyzed in PTC. The effects of
      neutralizing anti-Nrp2 antibody on VEGF-D-induced invasion and migration were
      assessed in PTC cell lines. RESULTS: Nrp2 expression was observed in 64.3% (36 of
      56) of the PTC patients. Nrp2 expression was significantly correlated with lymph
      node metastasis (P = 0.0216) and VEGF-D expression (P = 0.0034). VEGF-D was shown
      to promote filopodia formation and cancer cell migration and invasion by K1 and B
      CPAP cells. These responses were significantly blocked by neutralizing anti-Nrp2
      antibody. CONCLUSION: Nrp2 expression was correlated with lymph node metastasis
      and VEGF-D expression in PTC. Our data also showed a role for Nrp2 in regulating
      VEGF-D-induced invasion and migration in vitro.

PMID- 21880799
TI  - Pharmacokinetics and pharmacodynamics of oral and transdermal 17beta estradiol in
      girls with Turner syndrome.
AB  - CONTEXT: The type, dose, and route of 17beta-estradiol (E(2)) used to feminize
      girls with Turner syndrome (TS) is not well established. OBJECTIVE: The objective
      of the study was to characterize pharmacokinetics and pharmacodynamics of oral
      vs. transdermal E(2). SETTING: The study was conducted at a clinical research
      center. SUBJECTS: Ten girls with TS, mean age 17.7 +/- 0.4 (se) yr and 20
      normally menstruating controls (aged 16.8 +/- 0.4 yr) participated in the study.
      INTERVENTIONS: TS subjects were randomized 2 wk each to: low-dose daily oral (0.5
      mg) and biweekly transdermal E(2) (0.0375 mg) with 2 wk washout in between or
      high-dose oral (2.0 mg) and transdermal (0.075 mg), studied for 24 h each. Tandem
      mass spectrometry E(2) and estrone (E(1)) assays and a recombinant cell bioassay
      were used. RESULTS: Controls consisted of the following: E(2), 96 +/- 11 pg/ml
      (se), E(1), 70 +/- 7 (mean follicular/luteal). TS consisted of the following:
      E(2), average concentration on low-dose oral, 18 +/- 2.1 pg/ml, low-dose
      transdermal, 38 +/- 13, high-dose oral, 46 +/- 15, high-dose transdermal, 114 +/-
      31 pg/ml. E(1) concentrations were much higher on oral E(2) (low or high dose)
      than transdermal in TS and higher than controls. Bioestrogen was closest to
      normal in the high-dose transdermal group. LH and FSH decreased more in
      transdermal than oral low-dose routes and similarly in the high-dose oral and
      transdermal groups. IGF-I concentrations were variable (P = NS) among groups, and
      low-density lipoprotein/high-density lipoprotein cholesterol responses were
      variable. CONCLUSIONS: Transdermal E(2) results in E(2), E(1), and bioestrogen
      concentrations closer to normal and achieves greater suppression of LH/FSH in
      lower doses compared with normal. Whether the long-term metabolic effects of
      estrogen differ using the same form of E(2), depending on route, awaits further
      study in TS.

PMID- 21880800
TI  - Endothelin-1 stimulates proliferation of first-trimester trophoblasts via the A-
      and B-type receptor and invasion via the B-type receptor.
AB  - CONTEXT: Endothelin-1 (ET-1) stimulates proliferation and invasion of first
      trimester human trophoblast cells. OBJECTIVE: To test the hypothesis that ET-1
      effects are mediated by different receptor subtypes [ET receptor (ETR)-A and ETR
      B]. DESIGN: The location of ETR in trophoblast cell columns (wk 6-12) was
      investigated by immunohistochemistry and autoradiography. Trophoblasts were
      isolated from first-trimester human placentas and proliferative and invasive
      subpopulations separated using an integrin alpha6 antibody. Cells were incubated
      for 24 h with 10 MUm ET-1 and different ETR antagonists: PD142893 (unselective),
      BQ-610 (ETR-A), and RES-701-1 (ETR-B). After ETR down-regulation by antisense
      oligonucleotides, proliferation (thymidine incorporation, protein synthesis) and
      invasion (Matrigel invasion) were measured. ETR expression in isolated cells was
      analyzed by Western blotting and semiquantitative RT-PCR. RESULTS: Both ETR are
      expressed in both subpopulations in the cell column with predominance of ETR-A in
      the proximal part and proliferative subpopulation, whereas ETR-B is present at
      similar levels in both subpopulations. These results were confirmed at the mRNA
      level. ET-1 increased proliferation (maximum 267% of control) and invasion
      (maximum 288% of control) of first-trimester trophoblasts. The mitogenic ET-1
      effect was inhibited (P < 0.05) by 40-80% with each receptor antagonist and by 44
      and 40%, respectively, by ETR-A and ETR-B antisense oligonucleotides. The
      invasion-promoting effect was almost completely blocked in the presence of the
      ETR-B antagonists. CONCLUSION: The effect of ET-1 on cell proliferation in first
      trimester trophoblasts is mediated by both ETR, whereas its effect on invasion is
      mediated predominantly by ETR-B. These effects are in line with the receptor
      subtype location.

PMID- 21880801
TI  - GnRH-deficient phenotypes in humans and mice with heterozygous variants in
      KISS1/Kiss1.
AB  - CONTEXT: KISS1 is a candidate gene for GnRH deficiency. OBJECTIVE: Our objective
      was to identify deleterious mutations in KISS1. PATIENTS AND METHODS: DNA
      sequencing and assessment of the effects of rare sequence variants (RSV) were
      conducted in 1025 probands with GnRH-deficient conditions. RESULTS: Fifteen
      probands harbored 10 heterozygous RSV in KISS1 seen in less than 1% of control
      subjects. Of the variants that reside within the mature kisspeptin peptide,
      p.F117L (but not p.S77I, p.Q82K, p.H90D, or p.P110T) reduces inositol phosphate
      generation. Of the variants that lie within the coding region but outside the
      mature peptide, p.G35S and p.C53R (but not p.A129V) are predicted in silico to be
      deleterious. Of the variants that lie outside the coding region, one (g.1-3659C
      >T) impairs transcription in vitro, and another (c.1-7C->T) lies within the
      consensus Kozak sequence. Of five probands tested, four had abnormal baseline LH
      pulse patterns. In mice, testosterone decreases with heterozygous loss of Kiss1
      and Kiss1r alleles (wild-type, 274 +/- 99, to double heterozygotes, 69 +/- 16
      ng/dl; r(2) = 0.13; P = 0.03). Kiss1/Kiss1r double-heterozygote males have
      shorter anogenital distances (13.0 +/- 0.2 vs. 15.6 +/- 0.2 mm at P34, P <
      0.001), females have longer estrous cycles (7.4 +/- 0.2 vs. 5.6 +/- 0.2 d, P <
      0.01), and mating pairs have decreased litter frequency (0.59 +/- 0.09 vs. 0.71
      +/- 0.06 litters/month, P < 0.04) and size (3.5 +/- 0.2 vs. 5.4 +/- 0.3
      pups/litter, P < 0.001) compared with wild-type mice. CONCLUSIONS: Deleterious,
      heterozygous RSV in KISS1 exist at a low frequency in GnRH-deficient patients as
      well as in the general population in presumably normal individuals. As in
      Kiss1(+/-)/Kiss1r(+/-) mice, heterozygous KISS1 variants in humans may work with
      other genetic and/or environmental factors to cause abnormal reproductive
      function.

PMID- 21880802
TI  - Incidence of venous thromboembolism in patients with Cushing's syndrome: a
      multicenter cohort study.
AB  - CONTEXT: Venous thrombosis has frequently been reported in patients with
      endogenous Cushing's syndrome (CS). OBJECTIVE: The aim of this study was to
      evaluate the incidence of venous thromboembolism (VTE) in patients with CS prior
      to treatment and after surgery. DESIGN AND SETTING: We conducted a multicenter
      cohort study at all university medical centers in The Netherlands. PATIENTS:
      Consecutive patients diagnosed with endogenous CS of benign origin between
      January 1990 and June 2010 were eligible for inclusion. Patients surgically
      treated for nonfunctioning pituitary adenoma served as controls for the incidence
      of postoperative VTE in ACTH-dependent CS. MAIN OUTCOME MEASURES: We documented
      all objectively confirmed VTE during 3 yr prior to, and 3 yr after treatment
      onset. The incidences of VTE were expressed as incidence rates. RESULTS: A total
      of 473 patients (mean age 42 yr, 363 women) were included (360 ACTH-dependent
      pituitary CS). The total number of person-years was 2526. Thirty-seven patients
      experienced VTE during the study period, resulting in an incidence rate of 14.6
      [95% confidence interval (CI) 10.3-20.1] per 1000 person-years. The incidence
      rate for first-ever VTE prior to treatment was 12.9 (95% CI 7.5-12.6) per 1000
      person-years (17 events). The risk of postoperative VTE, defined as risk within 3
      months after surgery, was 0% for ACTH-independent and 3.4% (95% CI 2.0-5.9) for
      ACTH-dependent CS (12 events in 350 patients); most events occurred between 1 wk
      and 2 months after surgery. Compared with the controls, the risk of postoperative
      VTE in patients undergoing transsphenoidal surgery was significantly greater (P =
      0.01). CONCLUSIONS: Patients with CS are at high risk of VTE, especially during
      active disease and after pituitary surgery. Guidelines on thromboprophylaxis are
      urgently needed.

PMID- 21880803
TI  - Effect of lifestyle intervention on features of polycystic ovarian syndrome,
      metabolic syndrome, and intima-media thickness in obese adolescent girls.
AB  - CONTEXT: Polycystic ovarian syndrome (PCOS) is associated with cardiovascular
      risk factors (CRF). Lifestyle intervention is regarded as therapy of choice even
      if studies in adolescent girls with PCOS are scarce. OBJECTIVE: Our objective was
      to analyze the impact of lifestyle intervention on menses irregularities,
      hyperandrogenemia, CRF, and intima-media thickness (IMT) in adolescent girls with
      PCOS. PATIENTS: Patients included 59 obese girls with PCOS aged 12-18 yr.
      INTERVENTION: Intervention was a 1-yr lifestyle intervention based on nutrition
      education, exercise training, and behavior therapy. MAIN OUTCOME MEASURES: Menses
      cycles, IMT, waist circumference, blood pressure, fasting lipids, insulin,
      glucose, testosterone, dehydroepiandrosterone sulfate, androstenedione, and SHBG
      were evaluated. RESULTS: In contrast to the 33 girls without weight loss, the 26
      girls reducing their body mass index during the lifestyle intervention (by a mean
      of -3.9 kg/m(2)) improved most CRF and decreased their IMT (by a mean of -0.01
      cm). Testosterone concentrations decreased (by a mean of -0.3 nmol/liter) and
      SHBG concentrations increased (by a mean of +8 ng/ml) significantly in girls with
      weight loss in contrast to girls with increasing weight. The prevalence of
      amenorrhea (-42%) and oligoamenorrhea (-19%) decreased in the girls with weight
      loss. The changes in insulin in the 1-yr follow-up were significantly correlated
      to changes in testosterone (r = 0.38; P = 0.002) and SHBG (r = -0.35; P = 0.048).
      A linear regression model with changes in IMT as dependent variable demonstrated
      a significant association with changes in blood pressure and weight status but
      not with changes in testosterone. CONCLUSIONS: Weight loss due to lifestyle
      intervention is effective to treat menses irregularities, normalize androgens,
      and improve CRF and IMT in obese adolescent girls with PCOS.

PMID- 21880804
TI  - Postpartum assessment of the renin angiotensin system in women with previous
      severe, early-onset preeclampsia.
AB  - CONTEXT: Women with a history of severe preeclampsia are at an increased risk for
      the development of vascular disease. OBJECTIVE: We hypothesized that
      abnormalities in the renin-angiotensin system (RAS) may be a predisposing factor.
      DESIGN AND SETTING: Physiological assessments were conducted at an academic
      center. PARTICIPANTS: Sixteen women with previous severe preeclampsia (PPE) were
      compared with nine previously pregnant controls (PPC) and 11 never-pregnant
      controls (NPC). INTERVENTIONS: Baseline circulating components of the RAS and
      expression of angiotensin (ANG) II type I (AT1) and type II (AT2) receptors in
      the skin were assessed along with the response to simulated orthostatic stress
      using incremental lower-body negative pressure (LBNP: -15, -25, and -40 mm Hg)
      and a graded ANG II infusion (1 and 3 ng/kg . min). MAIN OUTCOME MEASURES:
      Response to LBNP and ANG II was evaluated. RESULTS: RAS components were not
      different between previously pregnant groups, but were decreased compared with
      NPC subjects. In response to LBNP, there were significant increases in RAS
      components in all three groups, but the response to this stimulus was
      significantly lower and delayed in PPE subjects. Despite the blunted rise in
      circulating RAS mediators in PPE subjects, their blood pressure was maintained in
      88% compared with only 33 and 55% in the PPC and NPC groups, respectively (P =
      0.014). All three groups responded to the graded ANG II infusion with an increase
      in blood pressure that was significantly more pronounced in PPE subjects (P =
      0.037) correlating with AT1/AT2 receptor expression. CONCLUSIONS: Alterations in
      the RAS in formerly preeclamptic patients may contribute to future vascular
      disease.

PMID- 21880805
TI  - Shift work at young age is associated with elevated long-term cortisol levels and
      body mass index.
AB  - BACKGROUND: The incidence of obesity and other features of the metabolic syndrome
      is increased in shift workers. This may be due to a misalignment between the
      internal circadian rhythm and the behavioral rhythm. The stress hormone cortisol
      could play a role in this phenomenon because it is secreted in a circadian
      rhythm, and long-term elevated cortisol leads to components of the metabolic
      syndrome. We compared cortisol levels in scalp hair of shift and day workers to
      study changes in long-term cortisol due to shift work. METHODS: Hair samples were
      collected from 33 shift workers and 89 day workers. Cortisol was extracted from
      the hair samples with methanol, and cortisol levels were measured using ELISA.
      Height and weight were measured, and body mass index (BMI) was calculated.
      RESULTS: Shift workers had higher hair cortisol levels than day workers: 47.32
      pg/mg hair [95% confidence interval (CI) = 38.37-58.21] vs. 29.72 pg/mg hair (95%
      CI = 26.18-33.73) (P < 0.001). When divided in age groups based on the median
      age, elevated cortisol levels were present only in younger shift workers: 48.53
      pg/mg hair (95% CI = 36.56-64.29) vs. 26.42 pg/mg hair (95% CI = 22.91-30.55) (P
      < 0.001). BMI was increased in younger shift workers as well: 27.2 (95% CI = 25.5
      28.8) vs. 23.7 (95% CI = 22.8-24.7) in young day workers (P = 0.001). Hair
      cortisol and BMI were positively correlated (beta = 0.262; P = 0.005).
      CONCLUSION: Shift work at a young adult age is associated with elevated long-term
      cortisol levels and increased BMI. Elevated cortisol levels and BMI may
      contribute to the increased cardiovascular risk found in shift workers.

PMID- 21880807
TI  - Whole-cell patch recording from Drosophila larval neurons.
AB  - The fruit fly Drosophila melanogaster has been instrumental in expanding our
      understanding of early aspects of neural development. The use of this model
      system has greatly added to our knowledge of neural cell-fate determination, axon
      guidance, and synapse formation. It has also become possible to access and make
      electrophysiological recordings directly from neurons in situ in an intact
      central nervous system (CNS), which has facilitated studies of the development
      and regulation of neuronal signaling. This protocol describes a procedure for
      revealing larval motor neurons and applying whole-cell patch recording techniques
      to these cells. The useful lifetime of first-instar larval preparations is ~30
      min, and that of third-instar CNS preparations is up to 1 h. It is therefore
      recommended that fresh preparations are used and that no breaks are taken during
      the procedure, although there may be time to pull and polish a patch pipette.

PMID- 21880806
TI  - Impact of mutational testing on the diagnosis and management of patients with
      cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA
      samples.
AB  - CONTEXT: Thyroid nodules are common in adults, but only a small fraction of them
      is malignant. Fine-needle aspiration (FNA) cytology provides a definitive
      diagnosis of benign or malignant disease in many cases, whereas about 25% of
      nodules are indeterminate, hindering most appropriate management. OBJECTIVE: The
      objective of the investigation was to study the clinical utility of molecular
      testing of thyroid FNA samples with indeterminate cytology. DESIGN: Residual
      material from 1056 consecutive thyroid FNA samples with indeterminate cytology
      was used for prospective molecular analysis that included the assessment of cell
      adequacy by a newly developed PCR assay and testing for a panel of mutations
      consisted of BRAF V600E, NRAS codon 61, HRAS codon 61, and KRAS codons 12/13
      point mutations and RET/PTC1, RET/PTC3, and PAX8/PPARgamma rearrangements.
      RESULTS: The collected material was adequate for molecular analysis in 967
      samples (92%), which yielded 87 mutations including 19 BRAF, 62 RAS, 1 RET/PTC,
      and five PAX8/PPARgamma. Four hundred seventy-nine patients who contributed 513
      samples underwent surgery. In specific categories of indeterminate cytology, i.e.
      atypia of undetermined significance/follicular lesion of undetermined
      significance, follicular neoplasm/suspicious for a follicular neoplasm, and
      suspicious for malignant cells, the detection of any mutation conferred the risk
      of histologic malignancy of 88, 87, and 95%, respectively. The risk of cancer in
      mutation-negative nodules was 6, 14, and 28%, respectively. Of 6% of cancers in
      mutation-negative nodules with atypia of undetermined significance/follicular
      lesion of undetermined significance cytology, only 2.3% were invasive and 0.5%
      had extrathyroidal extension. CONCLUSION: Molecular analysis for a panel of
      mutations has significant diagnostic value for all categories of indeterminate
      cytology and can be helpful for more effective clinical management of these
      patients.

PMID- 21880808
TI  - Dissection of third-instar Drosophila larvae for electrophysiological recording
      from neurons.
AB  - The fruit fly Drosophila melanogaster has been instrumental in expanding our
      understanding of early aspects of neural development. The use of this model
      system has greatly added to our knowledge of neural cell-fate determination, axon
      guidance, and synapse formation. It has also become possible to access and make
      electrophysiological recordings directly from neurons in situ in an intact
      central nervous system (CNS), which has facilitated studies of the development
      and regulation of neuronal signaling. It is possible to obtain
      electrophysiological recordings from all stages of Drosophila. Exposure of the
      intact Drosophila CNS is a prerequisite for such electrophysiological recordings.
      The dissection procedure described here is suitable for third-instar larvae. The
      dissection should take ~5 min to complete if all preparation work has been
      completed in advance. Owing to the short life span of the dissected larva, it is
      not recommended that the procedure be stopped or the preparation stored for later
      use.

PMID- 21880809
TI  - Dissection of first- and second-instar Drosophila larvae for electrophysiological
      recording from neurons: the flat (or fillet) preparation.
AB  - The fruit fly Drosophila melanogaster has been instrumental in expanding our
      understanding of early aspects of neural development. The use of this model
      system has greatly added to our knowledge of neural cell-fate determination, axon
      guidance, and synapse formation. It has also become possible to access and make
      electrophysiological recordings directly from neurons in situ in an intact
      central nervous system (CNS), which has facilitated studies of the development
      and regulation of neuronal signaling. It is possible to obtain
      electrophysiological recordings from all stages of Drosophila. Exposure of the
      intact Drosophila CNS is a prerequisite for such electrophysiological recordings.
      The dissection procedure described here can be applied to both late-stage embryos
      (stage 16 onward) and larvae. Because of their size, third-instar larvae are more
      difficult to flatten using this method and, if recording from this stage, the
      reader might consider using insect pins for the dissection or isolating the CNS
      using an alternative method. The dissection should take <10 min if all
      preparation work has been completed in advance. Owing to the short life span of
      the dissected larva, it is not recommended that the procedure be stopped or the
      preparation stored for later use.

PMID- 21880810
TI  - Single-particle virus tracking.
AB  - Real-time, live-cell imaging techniques and single-particle tracking algorithms
      can be used to follow individual virus particles as they infect cells. This
      protocol describes the use of one or more fluorescent markers to perform single
      particle virus-tracking experiments.

PMID- 21880811
TI  - Single-virus tracking in live cells.
AB  - Real-time, live-cell imaging techniques and single-particle tracking algorithms
      can be used to follow individual virus particles as they infect cells. This
      article describes the labeling of viruses and cellular structures with
      fluorescent probes to allow visualization in live cells. It also discusses how
      virus trajectories and virus-cell interactions can be imaged and analyzed.
      Methods used for time-lapse imaging are outlined, as are inhibitors and reagents
      used to study the role of the cellular machinery during viral infection.
      Algorithms for tracking virus particles and obtaining quantitative measurements
      of viral transport and virus-cell interactions are also included.

PMID- 21880812
TI  - Single-cell electroporation of Xenopus tadpole tectal neurons.
AB  - Single-cell electroporation (SCE) is a versatile technique for delivering
      electrically charged macromolecules, including DNA, RNA, synthetic
      oligonucleotides, peptides, dyes, and drugs, to individual cells within intact
      tissues. Here, we describe methods for SCE of single tectal neurons within the
      albino Xenopus laevis tadpole for delivery of plasmid DNA-expressing protein
      fluorophores or fluorescent dye. Individual neurons labeled by this technique can
      then be imaged in three dimensions (3D) within the intact and living brain using
      in vivo two-photon microscopy for studies of morphology and growth. The SCE
      protocol is relatively simple and requires minimal and common laboratory
      equipment, including a fluorescent stereomicroscope, micropipette puller, and
      electrical stimulator. Once equipment is set up, learning to label cells with
      fluorescent dyes is straightforward and usually quickly achieved, because direct
      visualization with fluorescent microscopy offers immediate feedback of success.
      The main challenges are positioning the pipette tip in a cell body layer and
      optimizing pipette tip shape and stimulation parameters. Once fluorescent dye
      loading has been achieved, transfecting neurons with DNA should follow by using
      the same pipette tip parameters, but extending the stimulation parameters,
      because plasmid DNA is larger than dye and requires formation of larger pores.
      Detectable expression of protein fluorophores from transfected DNA typically
      takes 6-12 h. SCE for dye loading or DNA transfection of tadpole tectal neurons
      is highly efficient and can be learned in 1 or 2 d by novice laboratory
      personnel.

PMID- 21880813
TI  - Single-cell electroporation in Xenopus.
AB  - Single-cell electroporation (SCE) is a versatile technique for delivering
      electrically charged macromolecules including DNA, RNA, synthetic
      oligonucleotides, peptides, dyes, and drugs to individual cells within intact
      tissues. Here, we describe methods for in vivo-targeted electroporation of single
      tectal neurons within the albino Xenopus laevis tadpole. Focal electroporation is
      achieved using a pipette electrode filled with a solution of the delivery
      molecules and with a tip diameter much smaller than the width of the target cell.
      The small tip allows for localization of an electric field, which restricts pore
      formation to only the individual cell in direct contact with the tip. Thus, the
      small tip permits focal delivery of the charged molecules within the pipette into
      individual cells. Factors affecting the efficiency of SCE, as well as various
      applications of this technique, are discussed. Particular focus is directed
      toward combining SCE with in vivo two-photon microscopy for three-dimensional
      (3D) imaging of neuron growth and cell-autonomous effects of altered protein
      function.

PMID- 21880814
TI  - Mounting Caenorhabditis elegans embryos for live imaging of embryogenesis.
AB  - Caenorhabditis elegans has been a key model organism for biomedical research.
      Light microscopy has played a central role in C. elegans biology. C. elegans is
      transparent throughout its life cycle, and its physical size, from 50 um
      (embryos) to 1 mm (adults), is well suited for light microscopy. Furthermore, it
      has an invariant body plan that arises from an invariant cell lineage. A wide
      range of biological processes, from patterns of gene expression to cell migration
      to neuronal activity, can be readily observed in single cells with a well-defined
      developmental context. This protocol describes how to collect and mount young C.
      elegans embryos for live imaging throughout embryogenesis.

PMID- 21880815
TI  - Gene set analysis and network analysis for genome-wide association studies.
AB  - The application of high-throughput genotyping in humans has yielded numerous
      insights into the genetic basis of human phenotypes and an unprecedented amount
      of genetic data. Genome-wide association studies (GWAS) have increased in number
      in recent years, but the variants that have been found have generally explained
      only a tiny proportion of the estimated genetic contribution to phenotypic
      variation. This article summarizes the progress made in the development of gene
      set analysis (GSA) and network analysis for GWAS was a way to identify the
      underlying molecular processes of human phenotypes. It also highlights some
      promising findings and indicates future directions that may greatly enhance the
      analysis and interpretation of GWAS.

PMID- 21880816
TI  - Generation of human scFv antibody libraries: PCR amplification and assembly of
      light- and heavy-chain coding sequences.
AB  - The development of therapeutic antibodies for use in the treatment of human
      diseases has long been a goal for many researchers in the antibody field. One way
      to obtain these antibodies is through phage-display libraries constructed from
      human lymphocytes. This protocol describes the construction of human scFv (single
      chain antibody fragment) libraries using a short linker (GGSSRSS) or a long
      linker (GGSSRSSSSGGGGSGGGG). In this method, the individual rearranged heavy- and
      light-chain variable regions are amplified separately and are linked through a
      series of overlap polymerase chain reaction (PCR) steps to give the final scFv
      products that are used for cloning.

PMID- 21880817
TI  - Generation of human Fab antibody libraries: PCR amplification and assembly of
      light- and heavy-chain coding sequences.
AB  - The development of therapeutic antibodies for use in the treatment of human
      diseases has long been a goal for many researchers in the antibody field. One way
      to obtain these antibodies is through phage-display libraries constructed from
      human lymphocytes. This protocol describes the construction of human Fab
      (fragment antigen binding) antibody libraries. In this method, the individual
      rearranged heavy- and light-chain variable regions are amplified separately and
      are linked through a series of overlap polymerase chain reaction (PCR) steps to
      give the final Fab products that are used for cloning.

PMID- 21880818
TI  - Immunolabeling of cells grown attached to a substratum or in suspension with
      actin antibodies.
AB  - Actin is a major component of all eukaryotic cells and is highly conserved across
      species. The different isoforms of actin show a very high degree of homology, and
      almost all actins bind cytochalasins, phallotoxins, and DNase I. Actin is
      important for maintaining cell shape and for myosin-based movements in cells. In
      addition, the actin cytoskeleton is involved in localization of other molecules
      in the cytoplasm and in cellular compartmentalization. Polyclonal and monoclonal
      antibodies with different specificities are commercially available for labeling
      actin-containing structures in cells. This article describes a protocol for
      immunolabeling actin that works well for cells grown in tissue culture as
      monolayers and for cells grown in suspension cultures that can be attached to
      polylysine-coated coverslips.

PMID- 21880819
TI  - In situ hybridization to somatic chromosomes in Drosophila.
AB  - In situ hybridization was originally developed as a technique for visualizing and
      physically mapping specific sequences on Drosophila melanogaster polytene
      chromosomes. Hybridization techniques can also be used to localize sequences on
      smaller, diploid chromosomes, such as condensed mitotic chromosomes. Variations
      of the method also allow the hybridization of probes to chromosomes within intact
      cells and tissues, rather than to chromosomes isolated from their cellular
      context and flattened on slides. This article presents methods for hybridizing
      fluorescent probes to chromosomes in whole-mount Drosophila tissues. These
      methods allow the investigation of nuclear organization even at stages where
      chromosomes are decondensed (as in interphase) or, for other reasons, cannot be
      discriminated in the light microscope. Consequently, they are useful for
      addressing a variety of cell biological questions. In addition to enhancing our
      understanding of somatic chromosome organization, this experimental approach has
      also revealed interactions among meiotic chromosomes in Drosophila females, which
      spend much of meiosis in a compact ball called the karyosome. Fluorescent in situ
      hybridization (FISH) methods can also be used to karyotype individual nuclei
      using chromosome-specific markers. With appropriate fixation conditions,
      hybridization to chromosomal DNA can be performed in conjunction with
      immunostaining, allowing the colocalization of cellular or chromosomal proteins.

PMID- 21880820
TI  - Preparation of cuticles from unhatched first-instar Drosophila larvae.
AB  - The finely sculpted cuticle of Drosophila carries a rich array of morphological
      details. Thus, cuticle examination has had a central role in the history of
      genetics. Studies of the Drosophila cuticle have focused mainly on first-instar
      larvae and adult cuticular morphology. This protocol describes the preparation of
      cuticles from larvae that have not yet hatched from the egg. It is designed for
      sampling all eggs laid by one or more females. This can be particularly useful,
      for example, when a mutation produces embryos that are unable to hatch from the
      egg.

PMID- 21880821
TI  - Immunostaining of mitotic chromosomes from Drosophila larval brain.
AB  - Good mitotic chromosome preparations are essential for the immunolocalization of
      chromosomal proteins. Although methanol/acetic acid fixation techniques preserve
      chromosome morphology very well, they remove a substantial fraction of
      chromosomal proteins. We have developed fixation/immunostaining procedures,
      described here, that are suitable for the immunolocalization of proteinaceous
      components of metaphase chromosomes from larval Drosophila brain cells. These
      procedures result in good chromosomal quality with minimal removal of proteins.

PMID- 21880822
TI  - Preparation of simian foamy virus type-1 vectors.
AB  - Foamy viruses (FVs) are nonpathogenic retroviruses that offer opportunities for
      efficient and safe gene transfer in various cell types from different species.
      These viruses have unique replication mechanisms that are distinct from other
      retroviruses, which may give an advantage to FV-mediated gene transfer. This
      protocol describes a method for simian foamy virus type-1 (SFV-1) vector
      preparation and concentration. A transient transfection of vector and packaging
      constructs allows generation of the SFV-1 vector with titers of 10(7)/mL. The
      vectors can be further concentrated by 100-200-fold without significant loss of
      vector titer.

PMID- 21880824
TI  - Labeling mitochondria with JC-1.
AB  - JC-1 (5,5',6,6'-tetrachloro1,1',3,3'-tetramethylbenzimidazolylcarbocyanine
      iodide) dye has been used to monitor mitochondrial potential. The monomeric form
      has an emission maximum of ~529 nm. The dye at higher concentrations or
      potentials forms red fluorescent J-aggregates with an emission maximum at 590 nm.
      The ratio of this green/red fluorescence is independent of mitochondrial shape,
      density, or size, but depends only on the membrane potential. It has been used to
      study whether all mitochondria in the same cell are at the same potential and
      whether membrane potential in a single long mitochondrion is uniform. JC-1 has
      also been useful in flow-cytometry studies, because the membrane potential can be
      followed without the need for confocal microscopy. This protocol describes the
      labeling of mitochondria in cultured cells with JC-1.

PMID- 21880823
TI  - Photoacoustic imaging.
AB  - Photoacoustic imaging, which is based on the photoacoustic effect, has developed
      extensively over the last decade. Possessing many attractive characteristics such
      as the use of nonionizing electromagnetic waves, good resolution and contrast,
      portable instrumention, and the ability to partially quantitate the signal,
      photoacoustic techniques have been applied to the imaging of cancer, wound
      healing, disorders in the brain, and gene expression, among others. As a
      promising structural, functional, and molecular imaging modality for a wide range
      of biomedical applications, photoacoustic imaging can be categorized into two
      types of systems: photoacoustic tomography (PAT), which is the focus of this
      article, and photoacoustic microscopy (PAM). We first briefly describe the
      endogenous (e.g., hemoglobin and melanin) and the exogenous (e.g., indocyanine
      green [ICG], various gold nanoparticles, single-walled carbon nanotubes [SWNTs],
      quantum dots [QDs], and fluorescent proteins) contrast agents for photoacoustic
      imaging. Next, we discuss in detail the applications of nontargeted photoacoustic
      imaging. Recently, molecular photoacoustic (MPA) imaging has gained significant
      interest, and a few proof-of-principle studies have been reported. We summarize
      the current state of the art of MPA imaging, including the imaging of gene
      expression and the combination of photoacoustic imaging with other imaging
      modalities. Last, we point out obstacles facing photoacoustic imaging. Although
      photoacoustic imaging will likely continue to be a highly vibrant research field
      for years to come, the key question of whether MPA imaging could provide
      significant advantages over nontargeted photoacoustic imaging remains to be
      answered in the future.

PMID- 21880825
TI  - Live cell imaging of yeast.
AB  - The development of cloning vectors for green fluorescent protein (GFP) and the
      simplicity of yeast reverse genetics allow straightforward labeling of yeast
      proteins in living cells. Budding and fission yeast are therefore attractive
      organisms in which to study dynamic cellular processes such as growth, cell
      division, and morphogenesis using live cell fluorescence microscopy. This article
      focuses on methods to culture, mount, and observe budding yeast cells using three
      dimensional (3D) microscopy, but the methods are broadly applicable to other
      types of cells and other imaging techniques. The emphasis is on 3D imaging,
      because yeast cells are roughly spherical, and most organelles in yeast move in
      three dimensions. Three-dimensional imaging also makes it possible to apply image
      restoration methods (e.g., deconvolution) to obtain sharper images with better
      definition. This is important, because yeast cells are small (haploid
      Saccharomyces cerevisiae cells have a diameter of ~4-5 um) relative to the
      resolution of even the best optical microscope (~0.25 um).

PMID- 21880826
TI  - Transcranial two-photon imaging of the living mouse brain.
AB  - This protocol describes imaging of the living mouse brain through a thinned skull
      using two-photon microscopy. This transcranial two-photon laser-scanning
      microscope (TPLSM) imaging method allows high-resolution imaging of fluorescently
      labeled neurons, microglia, astrocytes, and blood vessels, as well as subcellular
      structures such as dendritic spines and axonal varicosities. The surgical
      procedure that is required to allow imaging thins the cranium so that it becomes
      optically transparent. Once learned, the surgery can be performed in ~30 min, and
      imaging can follow immediately. The procedure can be repeated multiple times,
      allowing brain cells and tissues to be studied in the same animals over short or
      long time intervals, depending on the design of the experiment. Two-photon
      imaging through a thinned and intact skull avoids side effects caused by skull
      removal and is a minimally invasive method for studying the living mouse brain
      under physiological and pathological conditions.

PMID- 21880827
TI  - Developing chemical genetic approaches to explore G protein-coupled receptor
      function: validation of the use of a receptor activated solely by synthetic
      ligand (RASSL).
AB  - Molecular evolution and chemical genetics have been applied to generate
      functional pairings of mutated G protein-coupled receptors (GPCRs) and
      nonendogenous ligands. These mutant receptors, referred to as receptors activated
      solely by synthetic ligands (RASSLs) or designer receptors exclusively activated
      by designer drugs (DREADDs), have huge potential to define physiological roles of
      GPCRs and to validate receptors in animal models as therapeutic targets to treat
      human disease. However, appreciation of ligand bias and functional selectivity of
      different ligands at the same receptor suggests that RASSLs may signal
      differently than wild-type receptors activated by endogenous agonists. We
      assessed this by generating forms of wild-type human M(3) muscarinic receptor and
      a RASSL variant that responds selectively to clozapine N-oxide. Although the
      RASSL receptor had reduced affinity for muscarinic antagonists, including
      atropine, stimulation with clozapine N-oxide produced effects very similar to
      those generated by acetylcholine at the wild-type M(3)-receptor. Such effects
      included the relative movement of the third intracellular loop and C-terminal
      tail of intramolecular fluorescence resonance energy transfer sensors and the
      ability of the wild type and evolved mutant to regulate extracellular signal
      regulated kinase 1/2 phosphorylation. Each form interacted similarly with beta
      arrestin 2 and was internalized from the cell surface in response to the
      appropriate ligand. Furthermore, the pattern of phosphorylation of specific
      serine residues within the evolved receptor in response to clozapine N-oxide was
      very similar to that produced by acetylcholine at the wild type. Such results
      provide confidence that, at least for the M(3) muscarinic receptor, results
      obtained after transgenic expression of this RASSL are likely to mirror the
      actions of acetylcholine at the wild type receptor.

PMID- 21880828
TI  - A novel method for the immunoquantification of UDP-glucuronosyltransferases in
      human tissue.
AB  - Glucuronidation is a major pathway of drug and xenobiotic metabolism that is
      catalyzed by members of the UDP-glucuronosyltransferase (UGT) family. Predicting
      the contribution of individual UGTs to drug metabolism would be of considerable
      value in drug development and would be greatly aided by the availability of
      detailed absolute expression levels of these proteins; this is hampered by the
      lack of purified protein standards because of the hydrophobic membrane-associated
      nature of UGTs and the consequential difficulties in expression and purification.
      Here we describe a novel solution to this problem by expressing UGTs in
      Escherichia coli as fusion proteins with ribonuclease S-peptide, targeted to the
      periplasm with the pelB leader sequence. After addition of ribonuclease S-protein
      to membrane extracts, a functional ribonuclease is reconstituted that provides a
      direct and absolute quantification of the amount of UGT fusion protein; this is
      subsequently used to generate standard curves for immunoquantification by
      immunoblotting. To illustrate the value of the method, we have quantified the
      expression of UGT1A1 and UGT1A6 in human liver and kidney microsomes using new
      isoform-specific antibodies developed against peptides from these proteins.
      Expression levels of both proteins in liver were highly variable (28- and 20
      fold, respectively) and correlated strongly with UGT enzyme activity toward the
      probe substrates bilirubin and 1-naphthol, respectively. The method is broadly
      applicable and provides a straightforward means of determining the absolute, as
      opposed to relative, quantities of UGT proteins present in human tissues.

PMID- 21880829
TI  - Effect of dose escalation on the in vivo oral absorption and disposition of
      glycylsarcosine in wild-type and Pept1 knockout mice.
AB  - This study evaluated the in vivo absorption and disposition of glycylsarcosine
      (GlySar), after escalating oral doses, in wild-type and peptide transporter 1
      (Pept1) knockout mice. [(3)H]GlySar was administered to mice at doses of 1, 10,
      100, 1000, and 5000 nmol/g b.wt. Serial blood samples were obtained over 480 min,
      the plasma was harvested, and the area under the plasma concentration-time curve
      (AUC) was determined. It was observed that the GlySar AUC was 60, 45, and 30%
      lower in knockout than wild-type mice when evaluated over 2, 4, and 8 h,
      respectively (p < 0.01). Plasma levels of GlySar reached a plateau at 90 min in
      knockout mice and then rose to a second plateau at 240 min. In wild-type mice,
      the plasma levels rose continuously to reach a single plateau at 90 min. When
      partial AUC (0-120 min) was used as an indicator for rate of absorption, there
      was a 60% reduction in GlySar absorption rate in knockout mice compared with wild
      type animals. Tissue distribution studies were also performed after 10 nmol/g
      oral doses of [(3)H]GlySar. When sampled 1 h after dosing, GlySar tissue
      concentrations were significantly lower in knockout versus wild-type mice and,
      with the exception of intestines, reflected differences in the systemic exposure
      of dipeptide between these two genotypes. Overall, PEPT1 ablation in mice
      resulted in significant reductions, in vivo, in the rate and extent of GlySar
      absorption. The AUC of GlySar was proportional to dose in both genotypes over 1
      to 100 nmol/g, with minor decrements at the two highest doses.

PMID- 21880830
TI  - Correction for nonspecific binding to various components of ultrafiltration
      apparatus and impact on estimating in vivo rat clearance for a congeneric series
      of 5-ethyl, 5-n-alkyl barbituric acids.
AB  - Accurately predicting in vivo metabolic clearance from in vitro liver microsomes
      or hepatocytes requires a good understanding of the factors contributing to the
      prediction. Although much work has concentrated on deriving scaling factors and
      optimizing the metabolic stability techniques for consistency and rigor, it is
      only relatively recently that the importance of binding to microsomes and
      hepatocytes has been appreciated. Ultrafiltration is often used to estimate
      binding to plasma proteins and microsomes, but the level of nonspecific binding
      (NSB) to the ultrafiltration apparatus has not been adequately described. We
      derive an equation to correct for NSB and demonstrate that this can significantly
      affect the estimate of binding to microsomes and improve the accuracy of scaling
      to in vivo clearance for a series of barbiturates.

PMID- 21880832
TI  - An ACE inhibitor improves vascular outcomes in a PKD model.

PMID- 21880831
TI  - Monocyte/macrophage chemokine receptor CCR2 mediates diabetic renal injury.
AB  - Monocyte/macrophage recruitment correlates strongly with the progression of renal
      impairment in diabetic nephropathy (DN). C-C chemokine receptor (CCR)2 regulates
      monocyte/macrophage migration into injured tissues. However, the direct role of
      CCR2-mediated monocyte/macrophage recruitment in diabetic kidney disease remains
      unclear. We report that pharmacological blockade or genetic deficiency of CCR2
      confers kidney protection in Ins2(Akita) and streptozotocin (STZ)-induced
      diabetic kidney disease. Blocking CCR2 using the selective CCR2 antagonist
      RS504393 for 12 wk in Ins2(Akita) mice significantly attenuated albuminuria, the
      increase in blood urea nitrogen and plasma creatinine, histological changes, and
      glomerular macrophage recruitment compared with vehicle. Furthermore, mice
      lacking CCR2 (CCR2(-/-)) mimicked CCR2 blockade by reducing albuminuria and
      displaying less fibronectin mRNA expression and inflammatory cytokine production
      compared with CCR2(+/+) mice, despite comparable blood glucose levels. Bone
      marrow-derived monocytes from CCR2(+/+) or CCR2(-/-) mice adoptively transferred
      into CCR2(-/-) mice reversed the renal tissue-protective effect in diabetic CCR2(
      /-) mice as evaluated by increased urinary albumin excretion and kidney
      macrophage recruitment, indicating that CCR2 is not required for monocyte
      migration from the circulation into diabetic kidneys. These findings provide
      evidence that CCR2 is necessary for monocyte/macrophage-induced diabetic renal
      injury and suggest that blocking CCR2 could be a novel therapeutic approach in
      the treatment of DN.

PMID- 21880833
TI  - Phosphorylation of eIF2alpha via the general control kinase, GCN2, modulates the
      ability of renal medullary cells to survive high urea stress.
AB  - The phosphorylation of the alpha-subunit of the eukaryotic translation initiation
      factor 2 (eIF2alpha) occurs under many stress conditions in mammalian cells and
      is mediated by one of four eIF2alpha kinases: PERK, PKR, GCN2, and HRI. Cells of
      the renal medulla are regularly exposed to fluctuating concentrations of urea and
      sodium, the extracellular solutes responsible for the high osmolality in the
      renal medulla, and thus the kidneys ability to concentrate the urine in times of
      dehydration. Urea stress is known to initiate molecular responses that diverge
      from those seen in response to hypertonic stress (NaCl). We show that urea
      inducible GCN2 activation initiates the phosphorylation of eIF2alpha and the
      downstream increase of activating transcription factor 3 (ATF3). Loss of GCN2
      sensitized cells to urea stress, increasing the expression of activated caspase-3
      and decreasing cell survival. Loss of GCN2 ablated urea-induced phosphorylation
      of eIF2alpha and reduced the expression of ATF3.

PMID- 21880834
TI  - TGF-beta1 mediates sirolimus and cyclosporine A-induced alteration of barrier
      function in renal epithelial cells via a noncanonical ERK1/2 signaling pathway.
AB  - The immunosuppressant drugs cyclosporine A (CsA) and sirolimus (SRL) used in
      combination demonstrated beneficial effects in organ transplantation, but this
      combination can also result in increased adverse effects. We previously showed
      that not only CsA treatment but also its combination with SRL decreased
      paracellular permeability in renal proximal tubular cells by modification of the
      tight junction proteins, claudins, through ERK1/2 signaling pathway. In this
      present study, evidence is presented that not only CsA but also the combination
      of CsA/SRL may have adverse effects on the barrier function of renal proximal
      cells, at least in part, through the expression of the cytokine transforming
      growth factor (TGF)-beta(1). CsA treatment upregulated TGF-beta(1) gene
      expression and this upregulation was enhanced when CsA and SRL were applied
      together. Addition of TGF-beta(1) (5 ng/ml) altered the barrier function with
      increased transepithelial electrical resistance (TER) and claudin-1 expression.
      Use of a TGF-beta(1)-blocking antibody or blockage of TGF-beta(1) receptor kinase
      activity with SD208 prevented the CsA- and CsA/SRL-induced increase in TER. No
      evidence was found in the present studies to indicate that CsA or CsA/SRL
      treatment activated the TGF-beta(1) Smad canonical signaling pathway, whereas
      addition of TGF-beta(1) (5 ng/ml) did activate the Smad pathway. Addition of the
      ERK1/2 signaling inhibitor U0126 was able to prevent the TGF-beta(1)-mediated
      increase in TER and claudin expression. It is most likely that the CsA- and
      CsA/SRL-induced increases in TGF-beta(1) expression may not be sufficient to
      trigger the Smad pathway but however may trigger other TGF-beta(1) receptor
      mediated signaling including the ERK1/2 signaling pathway.

PMID- 21880835
TI  - COX-2 disruption leads to increased central vasopressin stores and impaired urine
      concentrating ability in mice.
AB  - It was hypothesized that cyclooxygenase-2 (COX-2) activity promotes urine
      concentrating ability through stimulation of vasopressin (AVP) release after
      water deprivation (WD). COX-2-deficient (COX-2(-/-), C57BL/6) and wild-type (WT)
      mice were water deprived for 24 h, and water balance, central AVP mRNA and
      peptide level, AVP plasma concentration, and AVP-regulated renal transport
      protein abundances were measured. In male COX-2(-/-), basal urine output and
      water intake were elevated while urine osmolality was decreased compared with WT.
      Water deprivation resulted in lower urine osmolality, higher plasma osmolality in
      COX-2(-/-) mice irrespective of gender. Hypothalamic AVP mRNA level increased and
      was unchanged between COX-2(-/-) and WT after WD. AVP peptide content was higher
      in COX-2(-/-) compared with WT. At baseline, plasma AVP concentration was
      elevated in conscious chronically catheterized COX-2(-/-) mice, but after WD
      plasma AVP was unchanged between COX-2(-/-) and WT mice (43 +/- 11 vs. 70 +/- 16
      pg/ml). Renal V2 receptor abundance was downregulated in COX-2(-/-) mice.
      Medullary interstitial osmolality increased and did not differ between COX-2(-/-)
      and WT after WD. Aquaporin-2 (AQP2; cortex-outer medulla), AQP3 (all regions),
      and UT-A1 (inner medulla) protein abundances were elevated in COX-2(-/-) at
      baseline and further increased after WD. COX-2(-/-) mice had elevated plasma urea
      and creatinine and accumulation of small subcapsular glomeruli. In conclusion,
      hypothalamic COX-2 activity is not necessary for enhanced AVP expression and
      secretion in response to water deprivation. Renal medullary COX-2 activity
      negatively regulates AQP2 and -3. The urine concentrating defect in COX-2(-/-) is
      likely caused by developmental glomerular injury and not dysregulation of AVP or
      collecting duct aquaporins.

PMID- 21880836
TI  - Endogenous BMP-7 is a critical molecular determinant of the reversibility of
      obstruction-induced renal injuries.
AB  - Although obstructive uropathies are frequently correctable through surgery, the
      potential for permanent renal injury remains even following the successful
      correction of obstructions. Little is known about the intrinsic mechanisms that
      determine the reversibility of renal injuries. We and others found that exogenous
      bone morphogenic protein 7 (BMP-7) inhibits the pathogenesis of renal injury.
      Here, we examine the role of endogenous BMP-7 in the outcome of renal recovery
      following the correction of obstructive uropathies using a reversible murine
      model of ureteral obstruction. The role of BMP-7 was determined by examining the
      regulation of BMP-7 during renal recovery and by treating with either BMP-7
      neutralizing antibodies or exogenous BMP-7. While BMP-7 is upregulated following
      the correction of obstructions that lead to reversible renal injury, the
      upregulation of BMP-7 is diminished following the correction of prolonged
      obstructions that lead to irreversible renal injury. The activation of the BMP-7
      pathway is required for several processes that contribute to renal recovery
      including the suppression of transforming growth factor-beta-dependent
      profibrotic pathways, the restoration of renal architecture, and the resolution
      of fibrotic changes in the kidney. Importantly, the therapeutic restoration of
      BMP-7 enhances renal recovery following the correction of prolonged obstructions
      that typically lead to irreversible renal injury. Together, these findings show
      that, while BMP-7 plays a critical role in the repair of obstruction-induced
      renal injuries, the potential for renal recovery from prolonged obstruction is
      diminished, in part, due to the dysregulation of BMP-7. Accordingly, renal
      recovery from obstructive uropathies may be optimized through timely intervention
      and adjuvant approaches to restore BMP-7 activity.

PMID- 21880837
TI  - The Western-style diet: a major risk factor for impaired kidney function and
      chronic kidney disease.
AB  - The Western-style diet is characterized by its highly processed and refined foods
      and high contents of sugars, salt, and fat and protein from red meat. It has been
      recognized as the major contributor to metabolic disturbances and the development
      of obesity-related diseases including type 2 diabetes, hypertension, and
      cardiovascular disease. Also, the Western-style diet has been associated with an
      increased incidence of chronic kidney disease (CKD). A combination of dietary
      factors contributes to the impairment of renal vascularization, steatosis and
      inflammation, hypertension, and impaired renal hormonal regulation. This review
      addresses recent progress in the understanding of the association of the Western
      style diet with the induction of dyslipidemia, oxidative stress, inflammation,
      and disturbances of corticosteroid regulation in the development of CKD. Future
      research needs to distinguish between acute and chronic effects of diets with
      high contents of sugars, salt, and fat and protein from red meat, and to uncover
      the contribution of each component. Improved therapeutic interventions should
      consider potentially altered drug metabolism and pharmacokinetics and be combined
      with lifestyle changes. A clinical assessment of the long-term risks of whole
      body disturbances is strongly recommended to reduce metabolic complications and
      cardiovascular risk in kidney donors and patients with CKD.

PMID- 21880839
TI  - Detection of plum pox potyviral protein-protein interactions in planta using an
      optimized mRFP-based bimolecular fluorescence complementation system.
AB  - In previous studies, protein interaction maps of different potyviruses have been
      generated using yeast two-hybrid (YTH) systems, and these maps have demonstrated
      a high diversity of interactions of potyviral proteins. Using an optimized
      bimolecular fluorescence complementation (BiFC) system, a complete interaction
      matrix for proteins of a potyvirus was developed for the first time under in
      planta conditions with ten proteins from plum pox virus (PPV). In total, 52 of
      100 possible interactions were detected, including the self-interactions of CI,
      6K2, VPg, NIa-Pro, NIb and CP, which is more interactions than have ever been
      detected for any other potyvirus in a YTH approach. Moreover, the BiFC system was
      shown to be able to localize the protein interactions, which was typified for the
      protein self-interactions indicated above. Additionally, experiments were carried
      out with the P3N-PIPO protein, revealing an interaction with CI but not with CP
      and supporting the involvement of P3N-PIPO in the cell-to-cell movement of
      potyviruses. No self-interaction of the PPV helper component-proteinase (HC-Pro)
      was detected using BiFC in planta. Therefore, additional experiments with turnip
      mosaic virus (TuMV) HC-Pro, PPV_HC-Pro and their mutants were conducted. The self
      interaction of TuMV_HCpro, as recently demonstrated, and the self-interaction of
      the TuMV_ and PPV_HC-Pro mutants were shown by BiFC in planta, indicating that HC
      Pro self-interactions may be species-specific. BiFC is a very useful and reliable
      method for the detection and localization of protein interactions in planta, thus
      enabling investigations under more natural conditions than studies in yeast
      cells.

PMID- 21880838
TI  - Defining protein expression in the urothelium: a problem of more than
      transitional interest.
AB  - The transitional epithelium of the bladder, the urothelium, is a challenging
      tissue to study due to its fragility, complex cellular makeup, stratified
      composition, and intimate connections to both neural and connective tissue
      elements. With the increasing focus on the urothelium as a mechanosensory tissue
      with complex autocrine and paracrine signaling activities, there have arisen a
      number of unresolved controversies in the urothelial literature regarding whether
      certain important sensory and signaling proteins are expressed by the urothelium.
      Prominent examples of this include the transient receptor potential (TRP) family
      member TRPV1 and the purinergic receptor P2X(3). The problem is more than one of
      scientific bookkeeping since studies utilizing genetic models (primarily knockout
      mice) claim additional credibility for urothelial functions when phenotypes are
      discovered. Furthermore, both of the above-mentioned receptors are important
      therapeutic targets for various bladder disorders including inflammatory and
      neuropathic pain. The reasons for the confusion about urothelial expression are
      manifold, but they likely include low expression levels in some cases, poor
      specificity of antibodies (sometimes lacking adequate controls), the presence of
      nonurothelial cells resident within the urothelium, and the fact that the
      urothelium is particularly prone to aspecific adsorption of antibodies. In this
      review, we attempt to summarize some of the pitfalls with currently accepted
      practices in this regard, as well as to describe a set of guidelines which will
      improve the reliability of conclusions related to urothelial expression. It is
      hoped that this will be of value to investigators studying the urothelium, to
      those attempting to interpret conflicts in the literature, and hopefully also
      those charged with reviewing unpublished work. These recommendations will outline
      a set of "baseline" and "best practice" guidelines by which both researchers and
      reviewers will be able to evaluate the evidence presented.

PMID- 21880840
TI  - Replication-incompetent influenza A viruses that stably express a foreign gene.
AB  - A biologically contained influenza A virus that stably expresses a foreign gene
      can be effectively traced, used to generate a novel multivalent vaccine and have
      its replication easily assessed, all while satisfying safety concerns regarding
      pathogenicity or reversion. This study generated a PB2-knockout (PB2-KO)
      influenza virus that harboured the GFP reporter gene in the coding region of its
      PB2 viral RNA (vRNA). Replication of the PB2-KO virus was restricted to a cell
      line stably expressing the PB2 protein. The GFP gene-encoding PB2 vRNA was stably
      incorporated into progeny viruses during replication in PB2-expressing cells. The
      GFP gene was expressed in virus-infected cells with no evidence of recombination
      between the recombinant PB2 vRNA and the PB2 protein mRNA. Furthermore, other
      reporter genes and the haemagglutinin and neuraminidase genes of different virus
      strains were accommodated by the PB2-KO virus. Finally, the PB2-KO virus was used
      to establish an improved assay to screen neutralizing antibodies against
      influenza viruses by using reporter gene expression as an indicator of virus
      infection rather than by observing cytopathic effect. These results indicate that
      the PB2-KO virus has the potential to be a valuable tool for basic and applied
      influenza virus research.

PMID- 21880841
TI  - Tumour susceptibility gene 101 and the vacuolar protein sorting pathway are
      required for the release of hepatitis E virions.
AB  - We have previously demonstrated that an intact PSAP motif in the ORF3 protein is
      required for the formation and release of membrane-associated hepatitis E virus
      (HEV) particles with ORF3 proteins on their surface. In this study, we
      investigated the direct interaction between the ORF3 protein and tumour
      susceptibility gene 101 (Tsg101), a cellular factor involved in the budding of
      viruses containing the P(T/S)AP late-domain, in PLC/PRF/5 cells expressing the
      wild-type or PSAP-mutated ORF3 protein and Tsg101 by co-immunoprecipitation.
      Tsg101 bound to wild-type ORF3 protein, but not to the PSAP-inactive ORF3
      protein. To examine whether HEV utilizes the multivesicular body (MVB) pathway to
      release the virus particles, we analysed the efficiency of virion release from
      cells upon introduction of small interfering RNA (siRNA) against Tsg101 or
      dominant-negative (DN) mutants of Vps4 (Vps4A and Vps4B). The relative levels of
      virus particles released from cells depleted of Tsg101 decreased to 6.4 % of
      those transfected with negative control siRNA. Similarly, virion egress was
      significantly reduced by the overexpression of DN forms (Vps4AEQ or Vps4BEQ). The
      relative levels of virus particles released from cells expressing Vps4AEQ and
      Vps4BEQ were 19.2 and 15.6 %, respectively, while the overexpression of wild-type
      Vps4A and Vps4B did not alter the levels of virus release. These results indicate
      that the ORF3 protein interacts with Tsg101 through the PSAP motifs in infected
      cells, and that Tsg101 and the enzymic activities of Vps4A and Vps4B are involved
      in HEV release, thus suggesting that HEV requires the MVB pathway for egress of
      virus particles.

PMID- 21880842
TI  - Genomic characterization of a novel human adenovirus type 31 recombinant in the
      hexon gene.
AB  - A novel human recombinant adenovirus of species A (HAdV-A31 MZ) was isolated from
      a patient with acute gastroenteritis in Japan. The complete genome of HAdV-A31
      strain MZ contains 33 776 bp. Analysis of the hexon gene of HAdV-A31 MZ indicated
      that its hexon sequence is the result of a genetic recombination between those of
      HAdV-A31 and a close relative to HAdV-A12. The recombination sites were found
      around the border of hypervariable loops 1 and 2 in the hexon gene, which are the
      most important determinants for virus neutralization. Loops 1 and 2 of this virus
      were genetically related to HAdV-A12, whereas all other parts of the genome were
      highly similar to HAdV-A31. In order to understand the evolution of adenoviruses
      correctly and to avoid misidentification of HAdV types, we recommend
      characterizing not only the hexon gene, but also the penton base and fiber genes.

PMID- 21880843
TI  - The N-terminal 12 amino acids of tomato aspermy virus 2b protein function in
      infection and recombination.
AB  - The roles for various regions of the 2b protein in infection, hypervirulence and
      recombination were examined by introducing stop codons in a chimeric virus
      containing RNA 1 from the cucumber mosaic virus (CMV strain Q), RNA 3 from the
      tomato aspermy virus (TAV) and RNA 2 of CMV with a 2b gene from TAV. Chimeric
      virus expressing the intact 2b protein induced severe symptoms in inoculated
      Nicotiana clevelandii and Nicotiana glutinosa and facilitated CMV-TAV
      recombination, while chimeric viruses not expressing 2b protein did not infect
      plants systemically. Chimeric viruses expressing either the N-terminal 43 or 12
      aa of the 2b protein infected both plant species systemically and facilitated CMV
      TAV recombination, but induced mild symptoms and no symptoms in the infected
      plants, respectively. These data suggest that oligopeptides can have important
      functions in the biology of viruses and prompt a re-examination of existing small
      ORFs in sequenced virus genomes.

PMID- 21880844
TI  - Mixed methods research design for pragmatic psychoanalytic studies.
AB  - Calls for more rigorous psychoanalytic studies have increased over the past
      decade. The field has been divided by those who assert that psychoanalysis is
      properly a hermeneutic endeavor and those who see it as a science. A comparable
      debate is found in research methodology, where qualitative and quantitative
      methods have often been seen as occupying orthogonal positions. Recently, Mixed
      Methods Research (MMR) has emerged as a viable "third community" of research,
      pursuing a pragmatic approach to research endeavors through integrating
      qualitative and quantitative procedures in a single study design. Mixed Methods
      Research designs and the terminology associated with this emerging approach are
      explained, after which the methodology is explored as a potential integrative
      approach to a psychoanalytic human science. Both qualitative and quantitative
      research methods are reviewed, as well as how they may be used in Mixed Methods
      Research to study complex human phenomena.

PMID- 21880845
TI  - Association of dietary sodium and potassium intakes with albuminuria in normal
      weight, overweight, and obese participants in the Reasons for Geographic and
      Racial Differences in Stroke (REGARDS) Study.
AB  - BACKGROUND: Among obese adults, sodium intake has been associated with
      cardiovascular disease. Few data are available on sodium intake and albuminuria,
      a marker of kidney damage and risk factor for cardiovascular disease. OBJECTIVE:
      We examined the relation between dietary sodium and potassium intakes and the
      ratio of sodium to potassium (Na/K) with albuminuria by BMI in the Reasons for
      Geographic and Racial Differences in Stroke (REGARDS) Study (n = 30,239 adults
      aged >=45 y). DESIGN: A modified Block 98 food-frequency questionnaire was used
      for dietary assessment in 21,636 participants, and nutritional variables were
      categorized by sex-specific quintiles. Normal weight, overweight, and obese were
      defined as BMI (in kg/m(2)) categories of 18.5-24.9, 25-29.9, and >=30,
      respectively. Albuminuria was defined as a ratio (mg/g) of urinary albumin to
      creatinine of >=30. RESULTS: The prevalences of albuminuria were 11.5%, 11.6%,
      and 16.0% in normal-weight, overweight, and obese participants, respectively. The
      multivariable-adjusted ORs for albuminuria in a comparison of the highest with
      the lowest quintile of Na/K intake (>=1.12 to <0.70 for men and >=1.07 to <0.62
      for women) were 0.89 (95% CI: 0.65, 1.22), 1.08 (95% CI: 0.85, 1.36), and 1.28
      (95% CI: 1.02, 1.61) in normal-weight, overweight, and obese participants,
      respectively. The highest quintile of dietary sodium was associated with an
      increased OR for albuminuria in obese participants (OR: 1.44; 95% CI: 1.00, 2.07)
      but not in normal-weight or overweight participants. Dietary potassium was not
      associated with albuminuria. CONCLUSION: In obese adults, higher dietary Na/K and
      sodium intakes were associated with albuminuria.

PMID- 21880846
TI  - The effect of coffee on blood pressure and cardiovascular disease in hypertensive
      individuals: a systematic review and meta-analysis.
AB  - BACKGROUND: The effect of coffee and caffeine on blood pressure (BP) and
      cardiovascular disease (CVD) in hypertensive persons is uncertain. OBJECTIVE: The
      objective was to summarize the evidence on the acute and longer-term effects of
      caffeine and coffee intake on BP and on the association between habitual coffee
      consumption and risk of CVD in hypertensive individuals. DESIGN: A systematic
      review and meta-analysis of publications identified in a PubMed and EMBASE search
      up to 30 April 2011 was undertaken. Data were extracted from controlled trials on
      the effect of caffeine or coffee intake on BP change and from cohort studies on
      the association between habitual coffee consumption and CVD. RESULTS: In 5
      trials, the administration of 200-300 mg caffeine produced a mean increase of 8.1
      mm Hg (95% CI: 5.7, 10.6 mm Hg) in systolic BP and of 5.7 mm Hg (95% CI: 4.1, 7.4
      mm Hg) in diastolic BP. The increase in BP was observed in the first hour after
      caffeine intake and lasted >=3 h. In 3 studies of the longer-term effect (2 wk)
      of coffee, no increase in BP was observed after coffee was compared with a
      caffeine-free diet or was compared with decaffeinated coffee. Last, 7 cohort
      studies found no evidence of an association between habitual coffee consumption
      and a higher risk of CVD. CONCLUSIONS: In hypertensive individuals, caffeine
      intake produces an acute increase in BP for >=3 h. However, current evidence does
      not support an association between longer-term coffee consumption and increased
      BP or between habitual coffee consumption and an increased risk of CVD in
      hypertensive subjects.

PMID- 21880847
TI  - Hepatic iron stores are increased as assessed by magnetic resonance imaging in a
      Chinese population with altered glucose homeostasis.
AB  - BACKGROUND: Emerging scientific evidence has disclosed a correlation between iron
      metabolism and type 2 diabetes (T2D). OBJECTIVE: The objective of this study was
      to test the hypothesis that body iron stores are higher in a Chinese population
      with altered glucose homeostasis. DESIGN: Serum iron, ferritin, and soluble
      transferrin receptor concentrations were measured in 298 subjects, including 70
      subjects with normal glucose tolerance (NGT group), 60 subjects with prediabetes
      (prediabetes group), and 168 subjects with T2D (T2D group). Hepatic iron stores
      in 88 subjects were assessed by using a magnetic resonance imaging (MRI) T2*
      gradient-recalled-echo technique. A general linear model ANOVA was performed for
      comparisons between groups after adjustment for age and BMI. Stepwise multiple
      linear regression analysis was used to identify factors associated with the MRI
      estimated hepatic iron concentration (M-HIC). RESULTS: Mean (+/-SD) M-HIC and R2*
      values in the prediabetes and T2D groups were significantly higher than in the
      NGT group (M-HIC: 40.6 +/- 8.6 and 39.3 +/- 10.7 MUmol/g compared with 27.8 +/-
      9.1 MUmol/g; R2* values: 47.9 +/- 11.9 and 47.3 +/- 11.5 s(-1) compared with 34.9
      +/- 7.0 s(-1); all P < 0.01). No significant difference was shown in M-HIC and
      R2* values between prediabetes and T2D groups. The M-HIC independently
      contributed to 43.3% of the glycated hemoglobin variance after adjustment for
      main clinical indexes (P < 0.001). The proportions of subjects with mild hepatic
      iron overload in the NGT, prediabetes, and T2D groups were 12.5%, 70.6%, and
      63.6%, respectively. CONCLUSIONS: To our knowledge, our findings provide novel
      evidence to support the hypothesis of a mild iron overload in patients with
      prediabetes and T2D. A cohort study concerned with the effect of the attenuation
      of excess iron on glucose metabolism in a prediabetic population is warranted.

PMID- 21880848
TI  - Calcium and vitamin D supplements and health outcomes: a reanalysis of the
      Women's Health Initiative (WHI) limited-access data set.
AB  - BACKGROUND: Frequent use of personal, nonprotocol calcium supplements obscured an
      adverse effect of coadministered calcium and vitamin D (CaD) on cardiovascular
      risk in the Women's Health Initiative (WHI). OBJECTIVE: We investigated the
      effects of the use of personal calcium or vitamin D supplements on other outcomes
      in the WHI CaD Study (WHI CaD) by using the WHI limited-access clinical trials
      data set. DESIGN: The WHI CaD was a 7-y, randomized, placebo-controlled trial of
      CaD (1 g Ca/400 IU vitamin D daily) in 36,282 community-dwelling, postmenopausal
      women. The incidence of total cancer (excluding nonmelanoma skin cancers), breast
      and colorectal cancers, hip and total fracture, and mortality was assessed by
      using Cox proportional hazards models. RESULTS: In the WHI CaD, interactions
      between the use of either personal calcium or vitamin D supplements and CaD were
      found for total, breast, and colorectal cancers but not for fracture or
      mortality. In 15,646 women (43%) who were not taking personal calcium or vitamin
      D supplements at randomization, CaD significantly decreased the risk of total,
      breast, and invasive breast cancers by 14-20% and nonsignificantly reduced the
      risk of colorectal cancer by 17%. In women taking personal calcium or vitamin D
      supplements, CaD did not alter cancer risk (HR: 1.06-1.26). CONCLUSIONS: For
      women in the WHI CaD who were not taking personal calcium or vitamin D
      supplements at randomization, CaD decreased the risk of total, breast, and
      colorectal cancers and did not change the risk of fractures or total mortality.
      The nonskeletal effects of CaD may be more important than the skeletal effects
      and should be considered when evaluating these supplements. The WHI CaD trial is
      registered at clinicaltrials.gov as NCT00000611.

PMID- 21880849
TI  - Experimental model of tuberculosis in the domestic goat after endobronchial
      infection with Mycobacterium caprae.
AB  - Caprine tuberculosis (TB) has increased in recent years, highlighting the need to
      address the problem the infection poses in goats. Moreover, goats may represent a
      cheaper alternative for testing of prototype vaccines in large ruminants and
      humans. With this aim, a Mycobacterium caprae infection model has been developed
      in goats. Eleven 6-month-old goats were infected by the endobronchial route with
      1.5 * 10(3) CFU, and two other goats were kept as noninfected controls. The
      animals were monitored for clinical and immunological parameters throughout the
      experiment. After 14 weeks, the goats were euthanized, and detailed postmortem
      analysis of lung lesions was performed by multidetector computed tomography
      (MDCT) and direct observation. The respiratory lymph nodes were also evaluated
      and cultured for bacteriological analysis. All infected animals were positive in
      a single intradermal comparative cervical tuberculin (SICCT) test at 12 weeks
      postinfection (p.i.). Gamma interferon (IFN-gamma) antigen-specific responses
      were detected from 4 weeks p.i. until the end of the experiment. The humoral
      response to MPB83 was especially strong at 14 weeks p.i. (13 days after SICCT
      boost). All infected animals presented severe TB lesions in the lungs and
      associated lymph nodes. M. caprae was recovered from pulmonary lymph nodes in all
      inoculated goats. MDCT allowed a precise quantitative measure of TB lesions.
      Lesions in goats induced by M. caprae appeared to be more severe than those
      induced in cattle by M. bovis over a similar period of time. The present work
      proposes a reliable new experimental animal model for a better understanding of
      caprine tuberculosis and future development of vaccine trials in this and other
      species.

PMID- 21880850
TI  - Development of a poliovirus neutralization test with poliovirus pseudovirus for
      measurement of neutralizing antibody titer in human serum.
AB  - In the Global Polio Eradication Initiative, laboratory diagnosis plays a critical
      role by isolating and identifying poliovirus (PV) from the stool samples from
      acute flaccid paralysis (AFP) cases. In recent years, reestablishment of PV
      circulation in countries where PV was previously eliminated has occurred because
      of decreased herd immunity, possibly due to poor vaccination coverage. To monitor
      the vulnerability of countries to PV circulation, surveillance of neutralizing
      antibody titers against PV in susceptible populations is essential in the end
      game of the polio eradication program. In this study, we have developed a PV
      neutralization test with type 1, 2, and 3 PV pseudoviruses to determine the
      neutralizing-antibody titer against PV in human serum samples. With this test,
      the neutralizing-antibody titer against PV could be determined within 2 days by
      automated interpretation of luciferase signals without using infectious PV
      strains. We validated the pseudovirus PV neutralization test with 131 human serum
      samples collected from a wide range of age groups (ages 1 to >60 years) by
      comparison with a conventional neutralization test. We found good correlation in
      the neutralizing-antibody titers determined by these tests. These results suggest
      that a pseudovirus PV neutralization test would serve as a safe and simple
      procedure for the measurement of the neutralizing-antibody titer against PV.

PMID- 21880851
TI  - Utility of immunoblotting for early diagnosis of toxoplasmosis seroconversion in
      pregnant women.
AB  - Congenital transmission of Toxoplasma gondii occurs mainly when a mother acquires
      the infection for the first time during pregnancy. It was recently shown that
      although early treatment of the primary infection during pregnancy has little or
      no impact on the fetomaternal transmission rate, it does reduce the incidence of
      sequelae in infected infants. Seroconversion is defined by the appearance of IgG.
      Commercial reagents continue to vary considerably in detecting low concentrations
      of antibodies, as during early seroconversion. We compared two routinely used
      immunoassays (IA) (Platelia and Elecsys Toxo IgG) and an indirect
      immunofluorescence assay (IIF) with a qualitative test based on immunoblot
      analysis (Toxo II IgG) (IB) to assess their abilities to diagnose seroconversion
      at its earliest stages. This prospective study was carried out between January
      and November 2010. It included 39 pregnant women with monthly follow-up who
      seroconverted during pregnancy. On first sera that were IgM positive but IgG
      negative (or equivocal) as detected by IA, IB diagnosed seroconversion twice as
      often as IIF (26/39 [66.7%] versus 13/39 [33.3%]; P < 0.001; chi(2) test). Serum
      samples were retaken 2 to 5 weeks later for the other 13 cases (IgG negative by
      IB on first serum). Seroconversion was demonstrated as follows: IB for 5 cases
      where IA remained negative or equivocal, IB and IIF for 5 cases where IA remained
      negative or equivocal, IA for 2 cases, and no method for 1 case (a third sample
      was necessary). In summary, IB permitted toxoplasmosis seroconversion diagnosis
      before other means in 92.3% of cases (36/39) and thus earlier therapeutic
      intervention.

PMID- 21880852
TI  - Analysis of bioplex syphilis IgG quantitative results in different patient
      populations.

PMID- 21880853
TI  - Multicenter evaluation of the Elecsys hepatitis B surface antigen quantitative
      assay.
AB  - The Elecsys hepatitis B surface antigen (HBsAg) II quantitative assay is a new
      quantitative electrochemiluminescence immunoassay which uses onboard dilution and
      a simple algorithm to determine HBsAg levels expressed in international units
      (IU)/ml (standardized against the World Health Organization [WHO] Second
      International Standard). This study evaluated its performance using routine serum
      samples from a wide range of HBsAg carriers and patients with chronic hepatitis B
      (CHB). HBsAg levels were measured in serum samples collected independently by
      five centers in Europe, Australia, and Asia. Serial dilution analyses were
      performed to assess the recommended dilution algorithm and determine the assay
      range free of hook effect. Assay precision was also established. Following
      assessment of serial dilutions (1:100 to 1:1,000,000) of the 611 samples
      analyzed, 70.0% and 85.6% of samples tested with analyzers incorporating 1:100
      (Elecsys 2010 and cobas e 411) and 1:400 (Modular Analytics E170) onboard
      dilution, respectively, fell within the linear range of the assay, providing a
      final result on the first test. No high-dose hook effect was seen up to the
      maximum HBsAg serum level tested (870,000 IU/ml) using the dilution algorithm.
      HBsAg levels were reliably determined across all hepatitis B virus (HBV)
      genotypes, phases of HBV infection, and stages of disease tested. Precision was
      high across all analyzers (% coefficient of variation [CV], 1.4 to 9.6; HBsAg
      concentrations, 0.1 to 37,300 IU/ml). The Elecsys HBsAg II quantitative assay
      accurately and reliably quantifies HBsAg in routine clinical samples. Onboard
      dilution minimizes retesting and reduces the potential for error.

PMID- 21880854
TI  - Dexamethasone-induced cytokine changes associated with diminished disease
      severity in horses infected with Anaplasma phagocytophilum.
AB  - Anaplasma phagocytophilum is the zoonotic cause of granulocytic anaplasmosis. We
      hypothesized that immune response, specifically gamma interferon (IFN-gamma),
      plays a role in disease severity. To test this, horses were infected and IFNG
      expression was pharmacologically downregulated using corticosteroids. Eight
      horses were infected with A. phagocytophilum; 4 received dexamethasone on days 4
      to 8 of infection. Clinical signs, hematologic parameters, and transcription of
      cytokine/chemokine genes were compared among treated and untreated horses.
      Infection was quantitated by msp2 real-time PCR and microscopy. As anticipated,
      there was significantly greater leukopenia, thrombocytopenia, and anemia in
      infected versus uninfected horses. The A. phagocytophilum load was higher for
      dexamethasone-treated horses. Dexamethasone reduced IFNG transcription by day 12
      and IL-8 and IL-18 by days 7 to 9 and increased IL-4 on day 7. The ratio of IL-10
      to IFNG was increased by dexamethasone on day 9. There were no hematologic
      differences between the infected horses. Dexamethasone suppression of
      proinflammatory response resulted in delayed infection-induced limb edema and
      decreased icterus, anorexia, and reluctance to move between days 6 and 9 and
      lower fever on day 7. These results underscore the utility of the equine model of
      granulocytic anaplasmosis and suggest that Th1 proinflammatory response plays a
      role in worsening disease severity and that disease severity can be decreased by
      modulating proinflammatory response. A role for Th1 response and macrophage
      activation in hematologic derangements elicited by A. phagocytophilum is not
      supported by these data and remains unproven.

PMID- 21880855
TI  - Age-specific seroprevalence of Merkel cell polyomavirus, BK virus, and JC virus.
AB  - We produced capsids of Merkel cell polyomavirus (MCPyV) in a baculovirus
      expression system and developed a virus-like particle (VLP) enzyme-linked
      immunosorbent assay (ELISA). To determine age-specific seroprevalence, serum
      samples were collected from 947 individuals attending hospital outpatient clinics
      and ranging in age from 1 to 93 years. To evaluate the association between
      exposure to MCPyV and Merkel cell cancer (MCC), plasma samples were obtained from
      33 MCC patients and 37 controls. MCPyV seroprevalence was 45% in children under
      10 years of age, increased to 60% in the next decade of life, and peaked at 81%
      among those 60 to 69 years of age. Levels of MCPyV capsid antibodies were
      positively correlated with age (P = 0.007). Virus specificity of MCPyV
      seroreactivity was supported by competitive inhibition of reactivity by MCPyV
      VLPs and not by BK polyomavirus (BKPyV) VLPs. MCPyV seroprevalence was greater
      among MCC patients (91%) than controls (68%; age-adjusted P value, 0.32); the
      mean level of MCPyV antibodies was also greater (P = 0.04). The age-specific
      seroprevalence of MCPyV shares with previously known polyomaviruses, BKPyV and JC
      polyomavirus (JCPyV), evidence of widespread exposure in human populations
      beginning early in life. MCPyV age-specific seroprevalence also has unique
      features. Seroprevalence among children is higher than that of JCPyV but lower
      than that of BKPyV. Among older adults, MCPyV seroprevalence remains high, while
      that of BKPyV declines and that of JCPyV continues to rise. In agreement with
      results from other studies, we found an association between MCPyV seropositivity
      and MCC, and higher levels of serum MCPyV capsid antibodies in MCC patients than
      in controls.

PMID- 21880856
TI  - Intranasal administration of an inactivated Yersinia pestis vaccine with
      interleukin-12 generates protective immunity against pneumonic plague.
AB  - Inhalation of Yersinia pestis causes pneumonic plague, which rapidly progresses
      to death. A previously licensed killed whole-cell vaccine is presently
      unavailable due to its reactogenicity and inconclusive evidence of efficacy. The
      present study now shows that vaccination intranasally (i.n.) with inactivated Y.
      pestis CO92 (iYp) adjuvanted with interleukin-12 (IL-12) followed by an i.n.
      challenge with a lethal dose of Y. pestis CO92 prevented bacterial colonization
      and protected 100% of mice from pneumonic plague. Survival of the vaccinated mice
      correlated with levels of systemic and lung antibodies, reduced pulmonary
      pathology and proinflammatory cytokines, and the presence of lung lymphoid cell
      aggregates. Protection against pneumonic plague was partially dependent upon Fc
      receptors and could be transferred to naive mice with immune mouse serum. On the
      other hand, protection was not dependent upon complement, and following
      vaccination, depletion of CD4 and/or CD8 T cells before challenge did not affect
      survival. In summary, the results demonstrate the safety, immunogenicity, and
      protective efficacy of i.n. administered iYp plus IL-12 in a mouse model of
      pneumonic plague.

PMID- 21880857
TI  - Evaluation of a recombinant Trypanosoma cruzi mucin-like antigen for
      serodiagnosis of Chagas' disease.
AB  - Chagas' disease is caused by the protozoan parasite Trypanosoma cruzi and is one
      of the most important endemic problems in Latin America. Lately, it has also
      become a health concern in the United States and Europe. Currently, a diagnosis
      of Chagas' disease and the screening of blood supplies for antiparasite
      antibodies are achieved by conventional serological tests that show substantial
      variation in the reproducibility and reliability of their results. In addition,
      the specificity of these assays is curtailed by antigenic cross-reactivity with
      sera from patients affected by other endemic diseases, such as leishmaniasis.
      Here we used a highly sensitive chemiluminescent enzyme-linked immunosorbent
      assay (CL-ELISA) to evaluate a recombinant protein core of a mucin-like molecule
      (termed trypomastigote small surface antigen [TSSA]) for the detection of
      specific serum antibodies in a broad panel of human sera. The same samples were
      evaluated by CL-ELISA using as the antigen either a mixture of native T. cruzi
      trypomastigote mucins or an epimastigote extract and, for further comparison, by
      conventional serologic tests, such as an indirect hemagglutination assay and
      indirect immunofluorescence assay. TSSA showed ~87% sensitivity among the
      seropositive Chagasic panel, a value which was increased up to >98% when only
      parasitologically positive samples were considered. More importantly, TSSA showed
      a significant increase in specificity (97.4%) compared to those of currently used
      assays, which averaged 80 to 90%. Overall, our data demonstrate that recombinant
      TSSA may be a useful antigen for the immunodiagnosis of Chagas' disease.

PMID- 21880858
TI  - Utility of IgM/IgG ratio and IgG avidity for distinguishing primary and secondary
      dengue virus infections using sera collected more than 30 days after disease
      onset.
AB  - Dengue virus (DV) IgM/IgG ratio and IgG avidity value (AV) can reliably
      distinguish between primary and secondary DV infections using sera collected
      within 30 days of disease onset, but little is known about their efficacies using
      sera collected >30 days after onset. To investigate this issue, we analyzed
      specimens submitted to our reference laboratory for DV antibody testing. We first
      classified patients as having primary (n = 55) or secondary (n = 58) infections
      based on seroconversion patterns in a comparison of two sera collected <30 days
      apart. We then evaluated IgM/IgG ratios and IgG AVs of the second specimens by
      using receiver operating characteristic curve analysis. The IgM/IgG ratio that
      best discriminated primary from secondary infection was 1.32; 95% of 55 primary
      infections exhibited ratios of >1.32, whereas 93% of 58 secondary infections
      exhibited ratios of <=1.32. The discriminatory AV was 0.39; 95% of 41 primary
      infections exhibited AVs of <=0.39, whereas 95% of 38 secondary infections
      exhibited AVs of >0.39. We then evaluated the IgM/IgG ratios and AV for primary
      infection patients whose second serum samples were collected >=30 days after the
      first serum samples; only 56% of 27 sera exhibited ratios of >1.32, whereas 81%
      of 21 sera exhibited AVs of <=0.39. Assuming that the first specimens were
      collected within a week after symptoms appeared, these findings indicate that IgG
      AV is superior to the IgM/IgG ratio for distinguishing primary from secondary DV
      infections when using samples collected more than 5 weeks after disease onset.

PMID- 21880859
TI  - Evolution of the vertebrate pth2 (tip39) gene family and the regulation of PTH
      type 2 receptor (pth2r) and its endogenous ligand pth2 by hedgehog signaling in
      zebrafish development.
AB  - In mammals, parathyroid hormone (PTH), secreted by parathyroid glands, increases
      calcium levels in the blood from reservoirs in bone. While mammals have two PTH
      receptor genes, PTH1R and PTH2R, zebrafish has three receptors, pth1r, pth2r, and
      pth3r. PTH can activate all three zebrafish Pthrs while PTH2 (alias
      tuberoinfundibular peptide 39, TIP39) preferentially activates zebrafish and
      mammalian PTH2Rs. We know little about the roles of the PTH2/PTH2R system in the
      development of any animal. To determine the roles of PTH2 and PTH2R during
      vertebrate development, we evaluated their expression patterns in developing
      zebrafish, observed their phylogenetic and conserved synteny relationships with
      humans, and described the genomic organization of pth2, pth2r, and pth2r splice
      variants. Expression studies showed that pth2 is expressed in cells adjacent to
      the ventral part of the posterior tuberculum in the diencephalon, whereas pth2r
      is robustly expressed throughout the central nervous system. Otic vesicles
      express both pth2 and pth2r, but heart expresses only pth2. Analysis of mutants
      showed that hedgehog (Hh) signaling regulates the expression of pth2 transcripts
      more than that of nearby gnrh2-expressing cells. Genomic analysis showed that a
      lizard, chicken, and zebra finch lack a PTH2 gene, which is associated with an
      inversion breakpoint. Likewise, chickens lack PTH2R, while humans lack PTH3R, a
      case of reciprocally missing ohnologs (paralogs derived from a genome
      duplication). The considerable evolutionary conservation in genomic structure,
      synteny relationships, and expression of zebrafish pth2 and pth2r provides a
      foundation for exploring the endocrine roles of this system in developing
      vertebrate embryos.

PMID- 21880860
TI  - Enzymological analysis of the tumor suppressor A-C1 reveals a novel group of
      phospholipid-metabolizing enzymes.
AB  - A-C1 protein is the product of a tumor suppressor gene negatively regulating the
      oncogene Ras and belongs to the HRASLS (HRAS-like suppressor) subfamily. We
      recently found that four members of this subfamily expressed in human tissues
      function as phospholipid-metabolizing enzymes. Here we examined a possible enzyme
      activity of A-C1. The homogenates of COS-7 cells overexpressing recombinant A-C1s
      from human, mouse, and rat showed a phospholipase A1/2 (PLA1/2) activity toward
      phosphatidylcholine (PC). This finding was confirmed with the purified A-C1. The
      activity was Ca2+ independent, and dithiothreitol and Nonidet P-40 were
      indispensable for full activity. Phosphatidylethanolamine (PE) was also a
      substrate and the phospholipase A1 (PLA1) activity was dominant over the PLA2
      activity. Furthermore, the protein exhibited acyltransferase activities
      transferring an acyl group of PCs to the amino group of PEs and the hydroxyl
      group of lyso PCs. As for tissue distribution in human, mouse, and rat, A-C1 mRNA
      was abundantly expressed in testis, skeletal muscle, brain, and heart. These
      results demonstrate that A-C1 is a novel phospholipid-metabolizing enzyme.
      Moreover, the fact that all five members of the HRASLS subfamily, including A-C1,
      show similar catalytic properties strongly suggests that these proteins
      constitute a new class of enzymes showing PLA1/2 and acyltransferase activities.

PMID- 21880862
TI  - Muscle protein metabolism responds similarly to exogenous amino acids in healthy
      younger and older adults during NO-induced hyperemia.
AB  - The combination of increasing blood flow and amino acid (AA) availability
      provides an anabolic stimulus to the skeletal muscle of healthy young adults by
      optimizing both AA delivery and utilization. However, aging is associated with a
      blunted response to anabolic stimuli and may involve impairments in endothelial
      function. We investigated whether age-related differences exist in the muscle
      protein anabolic response to AAs between younger (30 +/- 2 yr) and older (67 +/-
      2 yr) adults when macrovascular and microvascular leg blood flow were similarly
      increased with the nitric oxide (NO) donor, sodium nitroprusside (SNP).
      Regardless of age, SNP+AA induced similar increases above baseline (P <= 0.05) in
      macrovascular flow (4.3 vs. 4.4 ml.min(-1).100 ml leg(-1) measured using
      indocyanine green dye dilution), microvascular flow (1.4 vs. 0.8 video
      intensity/s measured using contrast-enhanced ultrasound), phenylalanine net
      balance (59 vs. 68 nmol.min(-1).100 ml.leg(-1)), fractional synthetic rate (0.02
      vs. 0.02%/h), and model-derived muscle protein synthesis (62 vs. 49 nmol.min(
      1).100 ml.leg(-1)) in both younger vs. older individuals, respectively. Provision
      of AAs during NO-induced local skeletal muscle hyperemia stimulates skeletal
      muscle protein metabolism in older adults to a similar extent as in younger
      adults. Our results suggest that the aging vasculature is responsive to exogenous
      NO and that there is no age-related difference per se in AA-induced anabolism
      under such hyperemic conditions.

PMID- 21880861
TI  - Symptom management in metastatic breast cancer.
AB  - Approximately 40,000 women die as a result of breast cancer each year and many
      more live with advanced disease. When breast cancer recurs, the goals of
      treatment often shift from one of cure to controlling the disease for as long as
      possible while palliating symptoms interfering with the patient's functional
      status and quality of life. This requires ongoing discussions with the patient
      and family about the goals of care. Many symptoms depend on the site of
      metastasis, with bone being the most frequent, and commonly occur with fatigue,
      depression, insomnia, and pain. The purpose of this paper is to identify and
      provide an overview of the management of the most common symptoms in patients
      with breast cancer metastases.

PMID- 21880863
TI  - Circadian integration of sleep-wake and feeding requires NPY receptor-expressing
      neurons in the mediobasal hypothalamus.
AB  - Sleep and feeding rhythms are highly coordinated across the circadian cycle, but
      the brain sites responsible for this coordination are unknown. We examined the
      role of neuropeptide Y (NPY) receptor-expressing neurons in the mediobasal
      hypothalamus (MBH) in this process by injecting the targeted toxin, NPY-saporin
      (NPY-SAP), into the arcuate nucleus (Arc). NPY-SAP-lesioned rats were initially
      hyperphagic, became obese, exhibited sustained disruption of circadian feeding
      patterns, and had abnormal circadian distribution of sleep-wake patterns. Total
      amounts of rapid eye movement sleep (REMS) and non-REMS (NREMS) were not altered
      by NPY-SAP lesions, but a peak amount of REMS was permanently displaced to the
      dark period, and circadian variation in NREMS was eliminated. The phase reversal
      of REMS to the dark period by the lesion suggests that REMS timing is
      independently linked to the function of MBH NPY receptor-expressing neurons and
      is not dependent on NREMS pattern, which was altered but not phase reversed by
      the lesion. Sleep-wake patterns were altered in controls by restricting feeding
      to the light period, but were not altered in NPY-SAP rats by restricting feeding
      to either the light or dark period, indicating that disturbed sleep-wake patterns
      in lesioned rats were not secondary to changes in food intake. Sleep
      abnormalities persisted even after hyperphagia abated during the static phase of
      the lesion. Results suggest that the MBH is required for the essential task of
      integrating sleep-wake and feeding rhythms, a function that allows animals to
      accommodate changeable patterns of food availability. NPY receptor-expressing
      neurons are key components of this integrative function.

PMID- 21880865
TI  - Species-specific inhibitor sensitivity of angiotensin-converting enzyme 2 (ACE2)
      and its implication for ACE2 activity assays.
AB  - Angiotensin-converting enzyme 2 (ACE2) is a component of the renin-angiotensin
      system, and its expression and activity have been shown to be reduced in
      cardiovascular diseases. Enzymatic activity of ACE2 is commonly measured by
      hydrolysis of quenched fluorescent substrates in the absence or presence of an
      ACE2-specific inhibitor, such as the commercially available inhibitor DX600.
      Whereas recombinant human ACE2 is readily detected in mouse tissues using 1 MUM
      DX600 at pH 7.5, the endogenous ACE2 activity in mouse tissues is barely
      detectable. We compared human, mouse, and rat ACE2 overexpressed in cell lines
      for their sensitivity to inhibition by DX600. ACE2 from all three species could
      be inhibited by DX600, but the half maximal inhibitory concentration (IC(50)) for
      human ACE2 was much lower (78-fold) than for rodent ACE2. Following optimization
      of pH, substrate concentration, and antagonist concentration, rat and mouse ACE2
      expressed in a cell line could be accurately quantified with 10 MUM DX600 (>95%
      inhibition) but not with 1 MUM DX600 (<75% inhibition). Validation that the
      optimized method robustly quantifies ACE2 in mouse tissues (kidney, brain, heart,
      and plasma) was performed using wild-type and ACE2 knockout mice. This study
      provides a reliable method for measuring human, as well as endogenous ACE2
      activity in rodents. Our data underscore the importance of validating the effect
      of DX600 on ACE2 from each particular species at the experimental conditions
      employed.

PMID- 21880864
TI  - Identification and apical membrane localization of an electrogenic Na+/Ca2+
      exchanger NCX2a likely to be involved in renal Ca2+ excretion by seawater fish.
AB  - Seawater (SW) contains ~10 mM Ca(2+), yet marine fish must drink seawater as
      their major water source. Thus marine teleosts fish need to excrete Ca(2+) to
      maintain whole body Ca(2+) homeostasis. In the intestine, seawater Ca(2+)
      interreacts with epithelial-secreted HCO(3)(-) by the intestinal epithelium, and
      the resulting CaCO(3) precipitates, which is rectally excreted. Recently the
      transporters involved in intestinal HCO(3)(-) secretion were identified. Ca(2+)
      is also excreted by the kidney, but the protein(s) involved in renal Ca(2+)
      excretion have not been identified. Here we identified a candidate transporter by
      using SW pufferfish torafugu (Takifugu rubripes) and its closely related
      euryhaline species mefugu (Takifugu obscurus), which are becoming useful animal
      models for studying molecular mechanisms of seawater adaptation. RT-PCR analyses
      of Na(+)/Ca(2+) exchanger (NCX) family members in various torafugu tissues
      demonstrated that only NCX2a is highly expressed in the kidney. Renal expression
      of NCX2a was markedly elevated when mefugu were transferred from freshwater to
      seawater. In situ hybridization and immunohistochemical analyses indicated that
      NCX2a is expressed in the proximal tubule at the apical membrane. NCX2a,
      expressed in Xenopus oocytes, conferred [Ca(2+)](out)- and Na(+)-dependent
      currents. These results suggest that NCX2a mediates renal Ca(2+) secretion at the
      apical membrane of renal proximal tubules and has an important role in whole body
      Ca(2+) homeostasis of marine teleosts.

PMID- 21880866
TI  - Local delivery of a PKCepsilon-activating peptide limits ischemia reperfusion
      injury in the aged female rat heart.
AB  - Reduced efficacy of cardioprotective interventions in the aged female heart,
      including estrogen replacement, highlights the need for alternative therapeutics
      to reduce myocardial ischemia-reperfusion (I/R) injury in postmenopausal women.
      Here, we sought to determine the efficacy of protein kinase-Cepsilon (PKCepsilon)
      mediated cardioprotection in the aged, estradiol-deficient rat heart. Infarct
      size and functional recovery were assessed in Langendorff-perfused hearts from
      adult (5 mo) or aged (23 mo) female Fisher 344 ovary-intact or ovariectomized
      (OVX) rats administered a PKCepsilon-activator, receptor for activated C kinase
      (psiepsilonRACK) prior to 47-min ischemia and 60-min reperfusion. Proteomic
      analysis was conducted on left ventricular mitochondrial fractions treated with
      psiepsilonRACK prior to I/R, utilizing isobaric tags for relative and absolute
      quantitation (iTRAQ) 8plex labeling and tandem mass spectrometry. Real-time PCR
      was utilized to assess connexin 43 (Cx43) and RACK2 mRNA post-I/R. Greater
      infarct size in aged OVX (78%) vs. adult (37%) was reduced by psiepsilonRACK
      (35%, P < 0.0001) and associated with greater mitochondrial PKCepsilon
      localization (P < 0.0003). Proteomic analysis revealed three novel mitochondrial
      targets of PKCepsilon-mediated cardioprotection with aging (P < 0.05): the
      antioxidant enzymes glutathione peroxidase (GPX) and MnSOD2, and heat shock
      protein 10. Finally, decreased levels of Cx43 and RACK2 mRNA seen with age were
      partially abrogated by administration of psiepsilonRACK (P < 0.05). The
      mechanisms described here may represent important therapeutic candidates for the
      treatment of acute myocardial infarction in postmenopausal women and age
      associated estradiol deficiency.

PMID- 21880868
TI  - Mitochondrial DNA polymerase gamma mutations: an ever expanding molecular and
      clinical spectrum.
AB  - Mutations in the POLG gene have emerged as one of the most common causes of
      inherited mitochondrial diseases in children and adults. This study sequenced the
      exons and flanking intronic regions of the POLG gene from 2697 unrelated patients
      with clinical presentations suggestive of POLG deficiency. Informative mutations
      have been identified in 136 unrelated individuals (5%), including 92 patients
      with two recessive pathogenic alleles and three patients harbouring a dominant
      mutation. Twenty-four novel recessive mutations and a novel possible dominant
      mutation, p.Y951N, were identified. All missense mutations occurred at
      evolutionarily conserved amino acids within functionally important regions
      identified by molecular modelling analyses. Oligonucleotide array comparative
      genomic hybridisation analyses performed on DNA samples from 81 patients with one
      mutant POLG allele identified a large intragenic deletion in only one patient,
      suggesting that large deletions in POLG are rare. The 92 patients with two mutant
      alleles exhibited a broad spectrum of disease. Almost all patients in all age
      groups had some degree of neuropathy. Seizures, hepatopathy, and lactic acidaemia
      were predominant in younger patients. By comparison, patients who developed
      symptoms in adulthood had a higher percentage of myopathy, sensory ataxia, and
      chronic progressive external ophthalmoplegia (CPEO)/ptosis. In conclusion, POLG
      mutations account for a broad clinical spectrum of mitochondrial disorders.
      Sequence analysis of the POLG gene should be considered as a part of routine
      screening for mitochondrial disorders, even in the absence of apparent
      mitochondrial DNA abnormalities.

PMID- 21880869
TI  - Oleuropein aglycone, an olive oil compound, ameliorates development of arthritis
      caused by injection of collagen type II in mice.
AB  - The aim of this study was to investigate the effect of oleuropein aglycone, an
      olive oil compound, on the modulation of the inflammatory response in mice
      subjected to collagen-induced arthritis (CIA). CIA was induced in mice by an
      intradermal injection of 100 MUl of an emulsion containing 100 MUg of bovine type
      II collagen (CII) and complete Freund's adjuvant (CFA) at the base of the tail.
      On day 21, a second injection of CII in CFA was administered. Mice developed
      erosive hind paw arthritis when immunized with CII in CFA. Macroscopic clinical
      evidence of CIA first appeared as periarticular erythema and edema in the hind
      paws. The incidence of CIA was 100% by day 28 in the CII-challenged mice and the
      severity of CIA progressed over a 35-day period with resorption of bone. The
      histopathology of CIA included erosion of the cartilage at the joint. Treatment
      with oleuropein aglycone starting at the onset of arthritis (day 25) ameliorated
      the clinical signs at days 26 to 35 and improved histological status in the joint
      and paw. The degree of oxidative and nitrosative damage was also significantly
      reduced in oleuropein aglycone-treated mice. Plasma levels of the proinflammatory
      cytokines were also significantly reduced by oleuropein aglycone. In addition, we
      have confirmed the beneficial effects of oleuropein aglycone on an experimental
      model of CIA in a therapeutic regimen of post-treatment, with treatment started
      at day 28, demonstrating that oleuropein aglycone exerts an anti-inflammatory
      effect during chronic inflammation and ameliorates the tissue damage associated
      with CIA.

PMID- 21880870
TI  - Opening of small and intermediate calcium-activated potassium channels induces
      relaxation mainly mediated by nitric-oxide release in large arteries and
      endothelium-derived hyperpolarizing factor in small arteries from rat.
AB  - This study was designed to investigate whether calcium-activated potassium
      channels of small (SK(Ca) or K(Ca)2) and intermediate (IK(Ca) or K(Ca)3.1)
      conductance activated by 6,7-dichloro-1H-indole-2,3-dione 3-oxime (NS309) are
      involved in both nitric oxide (NO) and endothelium-derived hyperpolarizing factor
      (EDHF)-type relaxation in large and small rat mesenteric arteries. Segments of
      rat superior and small mesenteric arteries were mounted in myographs for
      functional studies. NO was recorded using NO microsensors. SK(Ca) and IK(Ca)
      channel currents and mRNA expression were investigated in human umbilical vein
      endothelial cells (HUVECs), and calcium concentrations were investigated in both
      HUVECs and mesenteric arterial endothelial cells. In both superior (~1093 MUm)
      and small mesenteric (~300 MUm) arteries, NS309 evoked endothelium- and
      concentration-dependent relaxations. In superior mesenteric arteries, NS309
      relaxations and NO release were inhibited by both N(G),N(G)-asymmetric dimethyl-l
      arginine (ADMA) (300 MUM), an inhibitor of NO synthase, and apamin (0.5 MUM) plus
      1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34) (1 MUM), blockers of
      SK(Ca) and IK(Ca) channels, respectively. In small mesenteric arteries, NS309
      relaxations were reduced slightly by ADMA, whereas apamin plus an IK(Ca) channel
      blocker almost abolished relaxation. Iberiotoxin did not change NS309 relaxation.
      HUVECs expressed mRNA for SK(Ca) and IK(Ca) channels, and NS309 induced increases
      in calcium, outward current, and NO release that were blocked by apamin and TRAM
      34 or charybdotoxin. These findings suggest that opening of SK(Ca) and IK(Ca)
      channels leads to endothelium-dependent relaxation that is mediated mainly by NO
      in large mesenteric arteries and by EDHF-type relaxation in small mesenteric
      arteries. NS309-induced calcium influx appears to contribute to the formation of
      NO.

PMID- 21880872
TI  - CMS drops proposed payment reduction for 2012 inpatient PPS.

PMID- 21880873
TI  - Scorpion antivenin approved.

PMID- 21880871
TI  - Identification of chemosensitivity nodes for vinblastine through small
      interfering RNA high-throughput screens.
AB  - Discovering chemosensitivity pathways or nodes is an attractive strategy for
      formulating new drug combinations for cancer. Microtubules are among the most
      successful anticancer drug targets. Therefore, we implemented a small interfering
      RNA (siRNA) synthetic lethal screen targeting 5520 unique druggable genes to
      identify novel chemosensitivity nodes for vinblastine, a microtubule
      destabilizing agent used clinically. We transiently transfected human
      glioblastoma cells with siRNAs for 48 h and then treated cells with a sublethal
      concentration of vinblastine. Forty-eight hours later, we analyzed cell viability
      and, using a series of statistical methods, identified 65 gene products that,
      when suppressed, sensitized glioblastoma cells to vinblastine. After completion
      of the secondary assays, we focused on one siRNA, B-cell lymphoma extra large
      (BCL-xL), because of its role in the intrinsic apoptosis signaling pathway as
      well as the availability of pharmacological inhibitors. We found that nontoxic
      concentrations of 4-[4-[[2-(4-chlorophenyl)-5,5-dimethylcyclohexen-1
      yl]methyl]piperazin-1-yl]-N-[4-[[(2R)-4-morpholin-4-yl-1-phenylsulfanylbutan-2
      yl]amino]-3-(trifluoromethylsulfonyl)phenyl]sulfonylbenzamide (ABT-263), an
      inhibitor of the BCL-2 family members (BCL-2, BCL-xL, and BCL-w), sensitized
      glioblastoma and non-small-cell lung cancer cells to vinblastine and induced
      apoptosis through the intrinsic cell death pathway. These results illustrate the
      usefulness of unbiased siRNA screens as a method for identifying potential novel
      anticancer therapeutic combinations.

PMID- 21880875
TI  - IOM tells FDA to develop new regulatory pathway for medical devices.

PMID- 21880876
TI  - CMS Innovation Center starts gearing up.

PMID- 21880877
TI  - Short-term intubation after ingestion of Nicotiana glauca.

PMID- 21880878
TI  - Manually guided botulinum toxin type A submandibular injections for the treatment
      of sialorrhea in tube-fed patients with advanced amyotrophic lateral sclerosis.

PMID- 21880879
TI  - Pharmacists' perspectives on postgraduate training.

PMID- 21880880
TI  - Participation of clinical pharmacists without specialized infectious diseases
      training in antimicrobial stewardship.

PMID- 21880881
TI  - Assessing health literacy to identify patients for pharmacist-provided counseling
      on high-risk medications.

PMID- 21880882
TI  - Proposal for pharmacy residency leadership certificates.

PMID- 21880883
TI  - ASHP daily briefing.

PMID- 21880884
TI  - Clinical and economic benefits of aromatase inhibitor therapy in early-stage
      breast cancer.
AB  - PURPOSE: The clinical and economic benefits of aromatase inhibitor (AI) therapy
      in early-stage breast cancer are reviewed. SUMMARY: AI therapy has become a
      standard of care for the treatment of most postmenopausal women with early-stage
      breast cancer, as it significantly reduces the risk of disease recurrence and
      death. Using the currently accepted gold standard for clinical efficacy
      improvement in disease-free survival rather than overall survival-exemestane,
      anastrozole, or letrozole as monotherapy or in sequence with tamoxifen has been
      found to be superior to tamoxifen monotherapy. Emerging data have demonstrated
      potential overall survival advantages for AIs subsequent to and directly related
      to distant recurrence. Of the nonsteroidal AIs, letrozole appears to have the
      efficacy advantage by demonstrating an early effect on distant recurrence and,
      subsequently, a potentially significant overall survival benefit, though results
      of a prospective head-to-head trial of anastrozole and letrozole are not yet
      available. When the economic burden to society is considered, it appears that all
      AIs are similarly beneficial on the basis of disease recurrence. However,
      preliminary analyses indicate that the survival benefit appears to be greater
      with letrozole than with anastrozole. Thus, considering potential survival
      benefits and cost-effectiveness, letrozole may be preferable to anastrozole in
      the early adjuvant setting. CONCLUSION: AI therapy has become a standard of care
      for the treatment of most postmenopausal women with early-stage breast cancer.
      Emerging data have demonstrated potential overall survival advantages for AIs
      subsequent to and directly related to distant recurrence. When the economic
      burden to society is considered, it appears that all AIs are similarly beneficial
      on the basis of disease recurrence.

PMID- 21880885
TI  - Myoclonus associated with long-term use of diltiazem.
AB  - PURPOSE: A case of possible diltiazem-induced myoclonus in a patient receiving
      long-term therapy, with residual symptoms after discontinuation, is reported.
      SUMMARY: A 61-year-old Caucasian man who had received diltiazem therapy for 5
      years for the treatment of premature ventricular contractions (PVCs) was seen at
      a clinic for complaints of abnormal sensations and body movements that had
      worsened over 2 years and were sometimes triggered by an exaggerated startle
      response to light and startling scenes on television and in movies. After a sleep
      study, electroencephalography, and other evaluations to rule out neurologic and
      other causes of the patient's myoclonus, diltiazem therapy was discontinued; two
      weeks later, the man reported a 50% reduction in symptoms. At 1- and 3-year
      follow-up visits, the patient reported further diminution but not complete
      resolution of the myoclonic symptoms. In contrast to other published cases of
      calcium-channel-blocker-induced myoclonus, the onset of movement symptoms in this
      case was delayed, occurring years rather than days after the initiation of
      diltiazem use; the residual symptoms persisted far longer than in other reported
      cases. It is possible that the concomitant use of citalopram and a change in the
      patient's lipid-lowering medication may have contributed to or prolonged the
      abnormal movement symptoms in this case. Using the adverse drug reaction
      probability algorithm of Naranjo et al., the case was classified as possible
      diltiazem-induced myoclonus. CONCLUSION: A 61-year-old man developed myoclonus
      three years after starting diltiazem therapy for PVCs. The symptoms gradually
      resolved after the discontinuation of diltiazem but did not stop completely.

PMID- 21880886
TI  - Readministration of drotrecogin alfa (activated) in an adult with severe sepsis.
AB  - PURPOSE: The case of a patient with severe, multidrug-resistant, postoperative
      sepsis who was successfully treated with drotrecogin alfa (activated) on two
      occasions is reported. SUMMARY: After a thigh debridement procedure, a 55-year
      old African-American woman developed systemic inflammatory response syndrome
      (SIRS) secondary to necrotizing fasciitis. Despite empiric treatment including
      piperacillin-tazobactam and vancomycin, the patient remained severely
      hemodynamically unstable, exhibiting signs of multiorgan failure and requiring
      mechanical ventilation and the placement of a tracheostomy tube. After the
      administration of i.v. drotrecogin alfa (activated) 160 mg (24 MUg/kg/hr) over 96
      hours in combination with standard i.v. antimicrobials and vasopressin, the
      patient's hemodynamic status improved considerably. About three weeks later, the
      patient again developed SIRS that was refractory to standard therapies. After the
      results of laboratory cultures indicated ventilator-associated pneumonia due to
      multidrug-resistant Klebsiella pneumoniae, the woman received a second course of
      drotrecogin alfa and other therapies. Her condition improved and she was
      extubated and eventually transferred to a medical-surgical unit for continued
      care. While drotrecogin alfa, a recombinant form of human activated protein C
      (APC), has been shown to reduce mortality in adults with severe sepsis and acute
      organ dysfunction, previous reports indicated an increased risk of thrombotic
      events with the use of the drug, and there is speculation that the development of
      anti-APC antibodies might result in a diminished therapeutic response. In the
      case described here, there were no thrombotic events during or after either
      drotrecogin alfa infusion and no clinical evidence of antibody formation.
      CONCLUSION: A patient received two complete courses of drotrecogin alfa
      (activated) without any treatment-related complications.

PMID- 21880887
TI  - Effect of fondaparinux prophylaxis on anti-factor Xa concentrations in patients
      with morbid obesity.
AB  - PURPOSE: Anti-factor Xa values in morbidly obese patients receiving standard
      doses of fondaparinux sodium for the prevention of venous thromboembolism (VTE)
      were analyzed in a retrospective chart evaluation. SUMMARY: The administration of
      low-molecular-weight heparins to obese patients (body mass index [BMI] of >=30
      kg/m(2)) at the dose recommended for VTE prophylaxis has been reported to result
      in increased thromboembolic events and decreased anti-factor Xa levels, and some
      evidence indicates that weight-based dosing adjustments may be appropriate. To
      study this phenomenon among morbidly obese patients (BMI of >=40 kg/m(2)), a
      review of the charts of 45 adult patients for whom steady-state anti-factor Xa
      laboratory values were obtained after at least four fondaparinux injections was
      conducted; in all instances, fondaparinux sodium was given at the standard dose
      (2.5 mg once daily). Of the total of 47 anti-factor Xa values analyzed, 22 (47%)
      were below the study institution's target peak range (0.3-0.5 mg/L), 20 values
      (43%) were within the range, and 5 (11%) were above the range. No documented
      thromboembolic events occurred during hospitalization in the cases evaluated. A
      stepwise linear regression analysis of selected demographic and clinical
      variables indicated that better renal function, male sex, increased BMI, and
      fewer fondaparinux doses were associated with a greater likelihood of diminished
      anti-factor Xa activity in the cases evaluated. CONCLUSION: Anti-factor Xa
      concentrations in morbidly obese patients receiving fondaparinux sodium 2.5 mg
      subcutaneously daily for VTE prophylaxis were within or above the target range in
      53% of the instances evaluated.

PMID- 21880888
TI  - Stability of levothyroxine injection in glass, polyvinyl chloride, and polyolefin
      containers.
AB  - PURPOSE: The 24-hour stability of a levothyroxine solution admixed and stored in
      three common infusion containers and infused through polyvinyl chloride (PVC)
      tubing was evaluated. METHODS: Levothyroxine sodium 1-MUg/mL injection prepared
      in glass bottles and PVC and polyolefin bags were assayed using high-performance
      liquid chromatography at 0, 1, 3, 6, 12, and 24 hours; samples drawn directly
      from the containers, as well as from the distal end of attached PVC tubing, were
      assayed. The area under the time-versus-concentration curve (AUC) for predicted
      and delivered doses was calculated; analysis of variance was used for comparison
      of the percentages of predicted and actual AUC values. RESULTS: The levothyroxine
      concentration was stable in glass bottles and polyolefin bags through 24 hours
      (mean +/- S.D. percentage of initial concentration remaining, 103.5% +/- 2.5% and
      100.0% +/- 2.9%, respectively). In the PVC infusion bags, the amount of drug
      decreased to 90% of the initial concentration within 1 hour and then rose and
      remained within acceptability limits. The levothyroxine concentration of the
      samples infused through PVC line from glass and polyolefin containers decreased
      after 1 hour by about 13%; the loss of the drug from the samples infused from PVC
      bags was higher (18%), presumably due to additive adsorptive effects. In all
      samples tested, the drug concentration rebounded and remained above 90% to the
      end of the study. CONCLUSION: Levothyroxine sodium 1-MUg/mL solution was stable
      for 24 hours in glass bottles and polyolefin bags but when stored in PVC bags,
      the concentration decreased by 10% after 1 hour.

PMID- 21880889
TI  - Prevalence of articles with honorary and ghost authors in three pharmacy
      journals.
AB  - PURPOSE: The prevalence of honorary and ghost authors in articles published in
      2009 in three peer-reviewed pharmacy journals was studied. METHODS: A 20-question
      survey was e-mailed to corresponding authors of articles with two or more authors
      published in 2009 in the American Journal of Health-System Pharmacy, Annals of
      Pharmacotherapy, and Pharmacotherapy. The survey solicited the following
      information: demographic characteristics of the corresponding author, information
      about the published article, information to determine whether any of the authors
      did not meet the International Committee of Medical Journal Editors criteria for
      authorship, and information to determine if an individual contributed
      substantially to the research or writing of the article but was not listed as an
      author. RESULTS: Of the 491 corresponding authors to whom the survey was sent,
      457 had a working e-mail address; 114 surveys were completed (24.9% response
      rate). Usable responses were provided by 112 authors. The prevalence of articles
      with honorary and ghost authors was 14.3% and 0.9%, respectively. Honorary
      authorship was more common in original research than review articles. Articles
      with honorary authors had longer bylines than articles without honorary authors
      (mean number of authors, 4.9 versus 3.7; p = 0.002). The proportion of articles
      with an honorary author was 1.9% for articles with fewer than 4 authors, 25% for
      articles with 4 or 5 authors, and 29.4% for articles with more than 5 authors (p
      = 0.001). CONCLUSION: A survey sent to the corresponding authors of articles
      published in 2009 in three peer-reviewed pharmacy journals revealed that a
      substantial percentage of articles demonstrated evidence of honorary or ghost
      authorship.

PMID- 21880890
TI  - Women as authors in the pharmacy literature: 1989-2009.
AB  - PURPOSE: Trends in the authorship of original research articles by female U.S.
      pharmacists in three peer-reviewed pharmacy journals over the period 1989-2009
      were evaluated. METHODS: The sex distribution of the authors of all original
      research articles published in 1989, 1999, and 2009 in three prominent pharmacy
      journals (American Journal of Health-System Pharmacy, Annals of Pharmacotherapy,
      and Pharmacotherapy) was evaluated. A total of 608 original research articles
      were assessed to determine the sex of the first listed author (typically the
      person with primary responsibility for the research and article preparation) and
      the last listed, or "senior," author (usually a senior faculty member under whose
      academic purview the research was conducted). Pharmacist authors with U.S.
      affiliations were included in the analysis. RESULTS: In each of the three
      journals evaluated, female authorship increased from 1989 to 2009. Overall, the
      proportion of articles listing a woman as the first author increased
      significantly during the study period, from 29.9% in 1989 to 44.3% in 1999 and to
      52.2% in 2009. However, after a significant rise in the proportion of articles
      listing a woman as the last author from 1989 to 1999 (from 16.8% to 37.0%),
      female last authorship in the three journals declined to 33.8% in 2009.
      CONCLUSION: There was a significant overall increase in female authorship of
      original research articles in the pharmacy literature from 1989 to 2009, but
      gender difference persists among pharmacists serving as last listed authors.

PMID- 21880891
TI  - Development and implementation of an interdisciplinary oncology program in a
      community hospital.
AB  - PURPOSE: The development and implementation of an interdisciplinary oncology
      program in a community hospital are described. SUMMARY: Before the program was
      established, clinical pharmacists responsible for order entry and verification
      did not have a defined structure and resource to effectively communicate with
      medical oncologists and nurses on patient care issues and oncology drug
      information. The practice model did not meet practice needs, departmental safety,
      quality, or cost-saving goals. An interdisciplinary team was established to
      determine where current processes and procedures were needed to decrease errors
      and improve efficiency associated with chemotherapy services. Three stages of
      practice development were planned, and an interdisciplinary oncology program
      involving nursing and pharmacy team members and medical oncologists was
      established. Standardized order forms, various pharmacy collaborative agreements,
      protocols, improved oncology nursing and pharmacy processes, and established
      standards in order writing, dispensing, administration, and monitoring were
      developed. An oncology pharmacist specialist position was requested, and this
      pharmacist played an essential role in helping the hospital realize significant
      cost savings and improve the quality of care provided to patients receiving
      chemotherapy services. Data were collected for 96 chemotherapy orders before
      program implementation and for 75 orders after program implementation, and a 45%
      reduction in total error related to chemotherapy drugs was observed (p < 0.0625).
      The most common cause of errors was missing information, typically an omitted
      duration or frequency, dose, route, or premedication (63% of all errors
      documented). CONCLUSION: The development and implementation of an
      interdisciplinary oncology program resulted in decreased medication-error rates,
      expanded pharmacy services, and cost savings.

PMID- 21880892
TI  - Mechanism and cellular function of Bud6 as an actin nucleation-promoting factor.
AB  - Formins are a conserved family of actin assembly-promoting factors with diverse
      biological roles, but how their activities are regulated in vivo is not well
      understood. In Saccharomyces cerevisiae, the formins Bni1 and Bnr1 are required
      for the assembly of actin cables and polarized cell growth. Proper cable assembly
      further requires Bud6. Previously it was shown that Bud6 enhances Bni1-mediated
      actin assembly in vitro, but the biochemical mechanism and in vivo role of this
      activity were left unclear. Here we demonstrate that Bud6 specifically stimulates
      the nucleation rather than the elongation phase of Bni1-mediated actin assembly,
      defining Bud6 as a nucleation-promoting factor (NPF) and distinguishing its
      effects from those of profilin. We generated alleles of Bud6 that uncouple its
      interactions with Bni1 and G-actin and found that both interactions are critical
      for NPF activity. Our data indicate that Bud6 promotes filament nucleation by
      recruiting actin monomers to Bni1. Genetic analysis of the same alleles showed
      that Bud6 regulation of formin activity is critical for normal levels of actin
      cable assembly in vivo. Our results raise important mechanistic parallels between
      Bud6 and WASP, as well as between Bud6 and other NPFs that interact with formins
      such as Spire.

PMID- 21880893
TI  - MiR-637 maintains the balance between adipocytes and osteoblasts by directly
      targeting Osterix.
AB  - Bone development is dynamically regulated by homeostasis, in which a balance
      between adipocytes and osteoblasts is maintained. Disruption of this
      differentiation balance leads to various bone-related metabolic diseases,
      including osteoporosis. In the present study, a primate-specific microRNA (miR
      637) was found to be involved in the differentiation of human mesenchymal stem
      cells (hMSCs). Our preliminary data indicated that miR-637 suppressed the growth
      of hMSCs and induced S-phase arrest. Expression of miR-637 was increased during
      adipocyte differentiation (AD), whereas it was decreased during osteoblast
      differentiation (OS), which suggests miR-637 could act as a mediator of
      adipoosteogenic differentiation. Osterix (Osx), a significant transcription
      factor of osteoblasts, was shown to be a direct target of miR-637, which
      significantly enhanced AD and suppressed OS in hMSCs through direct suppression
      of Osx expression. Furthermore, miR-637 also significantly enhanced de novo
      adipogenesis in nude mice. In conclusion, our data indicated that the expression
      of miR-637 was indispensable for maintaining the balance of adipocytes and
      osteoblasts. Disruption of miR-637 expression patterns leads to irreversible
      damage to the balance of differentiation in bone marrow.

PMID- 21880894
TI  - A role for kinesin heavy chain in controlling vesicle transport into dendrites in
      Drosophila.
AB  - The unique architecture of neurons requires the establishment and maintenance of
      polarity, which relies in part on microtubule-based transport to deliver
      essential cargo into dendrites. To test different models of differential motor
      protein regulation and to understand how different compartments in neurons are
      supplied with necessary functional proteins, we studied mechanisms of dendritic
      transport, using Drosophila as a model system. Our data suggest that dendritic
      targeting systems in Drosophila and mammals are evolutionarily conserved, since
      mammalian cargoes are moved into appropriate domains in Drosophila. In a genetic
      screen for mutants that mislocalize the dendritic marker human transferrin
      receptor (hTfR), we found that kinesin heavy chain (KHC) may function as a
      dendritic motor. Our analysis of dendritic and axonal phenotypes of KHC loss-of
      function clones revealed a role for KHC in maintaining polarity of neurons, as
      well as ensuring proper axonal outgrowth. In addition we identified adenomatous
      polyposis coli 1 (APC1) as an interaction partner of KHC in controlling directed
      transport and modulating kinesin function in neurons.

PMID- 21880895
TI  - Two novel WD40 domain-containing proteins, Ere1 and Ere2, function in the
      retromer-mediated endosomal recycling pathway.
AB  - Regulated secretion, nutrient uptake, and responses to extracellular signals
      depend on cell-surface proteins that are internalized and recycled back to the
      plasma membrane. However, the underlying mechanisms that govern membrane protein
      recycling to the cell surface are not fully known. Using a chemical-genetic
      screen in yeast, we show that the arginine transporter Can1 is recycled back to
      the cell surface via two independent pathways mediated by the sorting nexins
      Snx4/41/42 and the retromer complex, respectively. In addition, we identify two
      novel WD40-domain endosomal recycling proteins, Ere1 and Ere2, that function in
      the retromer pathway. Ere1 is required for Can1 recycling via the retromer
      mediated pathway, but it is not required for the transport of other retromer
      cargoes, such as Vps10 and Ftr1. Biochemical studies reveal that Ere1 physically
      interacts with internalized Can1. Ere2 is present in a complex containing Ere1 on
      endosomes and functions as a regulator of Ere1. Taken together, our results
      suggest that Snx4/41/42 and the retromer comprise two independent pathways for
      the recycling of internalized cell-surface proteins. Moreover, a complex
      containing the two novel proteins Ere1 and Ere2 mediates cargo-specific
      recognition by the retromer pathway.

PMID- 21880896
TI  - Nuclear transporters in a multinucleated organism: functional and localization
      analyses in Aspergillus nidulans.
AB  - Nuclear transporters mediate bidirectional macromolecule traffic through the
      nuclear pore complex (NPC), thus participating in vital processes of eukaryotic
      cells. A systematic functional analysis in Aspergillus nidulans permitted the
      identification of 4 essential nuclear transport pathways of a hypothetical number
      of 14. The absence of phenotypes for most deletants indicates redundant roles for
      these nuclear receptors. Subcellular distribution studies of these carriers show
      three main distributions: nuclear, nucleocytoplasmic, and in association with the
      nuclear envelope. These locations are not specific to predicted roles as
      exportins or importins but indicate that bidirectional transport may occur
      coordinately in all nuclei of a syncytium. Coinciding with mitotic NPC
      rearrangements, transporters dynamically modified their localizations, suggesting
      supplementary roles to nucleocytoplasmic transport specifically during mitosis.
      Loss of transportin-SR and Mex/TAP from the nuclear envelope indicates absence of
      RNA transport during the partially open mitosis of Aspergillus, whereas nucleolar
      accumulation of Kap121 and Kap123 homologues suggests a role in nucleolar
      disassembly. This work provides new insight into the roles of nuclear
      transporters and opens an avenue for future studies of the molecular mechanisms
      of transport among nuclei within a common cytoplasm, using A. nidulans as a model
      organism.

PMID- 21880897
TI  - A pharmacological cocktail for arresting actin dynamics in living cells.
AB  - The actin cytoskeleton is regulated by factors that influence polymer assembly,
      disassembly, and network rearrangement. Drugs that inhibit these events have been
      used to test the role of actin dynamics in a wide range of cellular processes.
      Previous methods of arresting actin rearrangements take minutes to act and work
      well in some contexts, but can lead to significant actin reorganization in cells
      with rapid actin dynamics, such as neutrophils. In this paper, we report a
      pharmacological cocktail that not only arrests actin dynamics but also preserves
      the structure of the existing actin network in neutrophil-like HL-60 cells, human
      fibrosarcoma HT1080 cells, and mouse NIH 3T3 fibroblast cells. Our cocktail
      induces an arrest of actin dynamics that initiates within seconds and persists
      for longer than 10 min, during which time cells maintain their responsivity to
      external stimuli. With this cocktail, we demonstrate that actin dynamics, and not
      simply morphological polarity or actin accumulation at the leading edge, are
      required for the spatial persistence of Rac activation in HL-60 cells. Our drug
      combination preserves the structure of the existing cytoskeleton while blocking
      actin assembly, disassembly, and rearrangement, and should prove useful for
      investigating the role of actin dynamics in a wide range of cellular signaling
      contexts.

PMID- 21880898
TI  - Stimulation of the CLIP-170--dependent capture of membrane organelles by
      microtubules through fine tuning of microtubule assembly dynamics.
AB  - Cytoplasmic microtubules (MTs) continuously grow and shorten at their free plus
      ends, a behavior that allows them to capture membrane organelles destined for MT
      minus end-directed transport. In Xenopus melanophores, the capture of pigment
      granules (melanosomes) involves the +TIP CLIP-170, which is enriched at growing
      MT plus ends. Here we used Xenopus melanophores to test whether signals that
      stimulate minus end MT transport also enhance CLIP-170-dependent binding of
      melanosomes to MT tips. We found that these signals significantly (>twofold)
      increased the number of growing MT plus ends and their density at the cell
      periphery, thereby enhancing the likelihood of interaction with dispersed
      melanosomes. Computational simulations showed that local and global increases in
      the density of CLIP-170-decorated MT plus ends could reduce the half-time of
      melanosome aggregation by ~50%. We conclude that pigment granule aggregation
      signals in melanophores stimulate MT minus end-directed transport by the
      increasing number of growing MT plus ends decorated with CLIP-170 and
      redistributing these ends to more efficiently capture melanosomes throughout the
      cytoplasm.

PMID- 21880899
TI  - Neurobiology of tourette syndrome: current status and need for further
      investigation.
AB  - Tourette syndrome (TS) is a common, chronic neuropsychiatric disorder
      characterized by the presence of fluctuating motor and phonic tics. The typical
      age of onset is ~5-7 years, and the majority of children improve by their late
      teens or early adulthood. Affected individuals are at increased risk for the
      development of various comorbid conditions, such as obsessive-compulsive
      disorder, attention deficit hyperactivity disorder, school problems, depression,
      and anxiety. There is no cure for tics, and symptomatic therapy includes
      behavioral and pharmacological approaches. Evidence supports TS being an
      inherited disorder; however, the precise genetic abnormality remains unknown.
      Pathologic involvement of cortico-striatal-thalamo-cortical (CSTC) pathways is
      supported by neurophysiological, brain imaging, and postmortem studies, but
      results are often confounded by small numbers, age differences, severity of
      symptoms, comorbidity, use of pharmacotherapy, and other factors. The primary
      site of abnormality remains controversial. Although numerous neurotransmitters
      participate in the transmission of messages through CSTC circuits, a dopaminergic
      dysfunction is considered a leading candidate. Several animal models have been
      used to study behaviors similar to tics as well as to pursue potential
      pathophysiological deficits. TS is a complex disorder with features overlapping a
      variety of scientific fields. Despite description of this syndrome in the late
      19th century, there remain numerous unanswered neurobiological questions.

PMID- 21880900
TI  - Making sense of gray matter abnormalities in chronic orofacial pain--synthesizing
      divergent findings.

PMID- 21880901
TI  - Equiluminance cells in visual cortical area v4.
AB  - We report a novel class of V4 neuron in the macaque monkey that responds
      selectively to equiluminant colored form. These "equiluminance" cells stand apart
      because they violate the well established trend throughout the visual system that
      responses are minimal at low luminance contrast and grow and saturate as contrast
      increases. Equiluminance cells, which compose ~22% of V4, exhibit the opposite
      behavior: responses are greatest near zero contrast and decrease as contrast
      increases. While equiluminance cells respond preferentially to equiluminant
      colored stimuli, strong hue tuning is not their distinguishing feature-some
      equiluminance cells do exhibit strong unimodal hue tuning, but many show little
      or no tuning for hue. We find that equiluminance cells are color and shape
      selective to a degree comparable with other classes of V4 cells with more
      conventional contrast response functions. Those more conventional cells respond
      equally well to achromatic luminance and equiluminant color stimuli, analogous to
      color luminance cells described in V1. The existence of equiluminance cells,
      which have not been reported in V1 or V2, suggests that chromatically defined
      boundaries and shapes are given special status in V4 and raises the possibility
      that form at equiluminance and form at higher contrasts are processed in separate
      channels in V4.

PMID- 21880902
TI  - Lmx1a and lmx1b function cooperatively to regulate proliferation, specification,
      and differentiation of midbrain dopaminergic progenitors.
AB  - LIM homeodomain transcription factors, Lmx1a and Lmx1b, are required for the
      development of midbrain dopaminergic (mDA) neurons. Lmx1b is required for the
      specification and maintenance of mDA neurons, primarily due to its role in
      isthmic organizer development that is essential for the induction of mDA neurons.
      Here, we conditionally deleted Lmx1b in the ventral neural tube using ShhCre and
      found that Lmx1b conditional mutant mouse embryos show no defect in the
      development and maintenance of mDA neurons. In addition, Dreher (Lmx1a mutant)
      embryos display only a moderate reduction in the number of mDA neurons,
      suggesting that the related family member Lmx1b might compensate for Lmx1a
      function. We therefore generated Lmx1a and Lmx1b double mutants. Severe loss of
      mDA neurons occurred in Lmx1a(dr/dr);Shh(Cre/+);Lmx1b(f/f) double mutants due to
      essential roles for Lmx1a and Lmx1b in regulating the proliferation and neuronal
      commitment of mDA progenitors through the expression of Wnt1 and Ngn2,
      respectively. Lmx1a and Lmx1b also negatively regulate Hes1 expression and
      consequently cell cycle exit through activation of p27(Kip1) expression. In
      addition, Lmx1a and Lmx1b also regulate the expression of floor plate genes such
      as Corin and Slit2 and specification of postmitotic mDA neurons. These defects
      were more severe with decreasing gene dosage of Lmx1a and Lmx1b or observed only
      when all four copies of Lmx1a and Lmx1b genes were inactivated. Together, our
      results demonstrate that Lmx1a and Lmx1b function cooperatively to regulate
      proliferation, specification, and differentiation of mDA progenitors, including
      their floor plate-like properties.

PMID- 21880903
TI  - Essential role for vav Guanine nucleotide exchange factors in brain-derived
      neurotrophic factor-induced dendritic spine growth and synapse plasticity.
AB  - Brain-derived neurotrophic factor (BDNF) and its cognate receptor, TrkB, regulate
      a wide range of cellular processes, including dendritic spine formation and
      functional synapse plasticity. However, the signaling mechanisms that link BDNF
      activated TrkB to F-actin remodeling enzymes and dendritic spine morphological
      plasticity remain poorly understood. We report here that BDNF/TrkB signaling in
      neurons activates the Vav family of Rac/RhoA guanine nucleotide exchange factors
      through a novel TrkB-dependent mechanism. We find that Vav is required for BDNF
      stimulated Rac-GTP production in cortical and hippocampal neurons. Vav is
      partially enriched at excitatory synapses in the postnatal hippocampus but does
      not appear to be required for normal dendritic spine density. Rather, we observe
      significant reductions in both BDNF-induced, rapid, dendritic spine head growth
      and in CA3-CA1 theta burst-stimulated long-term potentiation in Vav-deficient
      mouse hippocampal slices, suggesting that Vav-dependent regulation of dendritic
      spine morphological plasticity facilitates normal functional synapse plasticity.

PMID- 21880904
TI  - Inhibitory dendrite dynamics as a general feature of the adult cortical
      microcircuit.
AB  - The mammalian neocortex is functionally subdivided into architectonically
      distinct regions that process various types of information based on their source
      of afferent input. Yet, the modularity of neocortical organization in terms of
      cell type and intrinsic circuitry allows afferent drive to continuously reassign
      cortical map space. New aspects of cortical map plasticity include dynamic
      turnover of dendritic spines on pyramidal neurons and remodeling of interneuron
      dendritic arbors. While spine remodeling occurs in multiple cortical regions, it
      is not yet known whether interneuron dendrite remodeling is common across primary
      sensory and higher-level cortices. It is also unknown whether, like pyramidal
      dendrites, inhibitory dendrites respect functional domain boundaries. Given the
      importance of the inhibitory circuitry to adult cortical plasticity and the
      reorganization of cortical maps, we sought to address these questions by using
      two-photon microscopy to monitor interneuron dendritic arbors of thy1-GFP-S
      transgenic mice expressing GFP in neurons sparsely distributed across the
      superficial layers of the neocortex. We find that interneuron dendritic branch
      tip remodeling is a general feature of the adult cortical microcircuit, and that
      remodeling rates are similar across primary sensory regions of different
      modalities, but may differ in magnitude between primary sensory versus higher
      cortical areas. We also show that branch tip remodeling occurs in bursts and
      respects functional domain boundaries.

PMID- 21880905
TI  - Training-induced neural plasticity in golf novices.
AB  - Previous neuroimaging studies in the field of motor learning have shown that
      learning a new skill induces specific changes of neural gray and white matter in
      human brain areas necessary to control the practiced task. Former longitudinal
      studies investigating motor skill learning have used strict training protocols
      with little ecological validity rather than physical leisure activities, although
      there are several retrospective and cross-sectional studies suggesting
      neuroprotective effects of physical leisure activities. In the present
      longitudinal MRI study, we used voxel-based morphometry to investigate training
      induced gray matter changes in golf novices between the age of 40 and 60 years,
      an age period when an active life style is assumed to counteract cognitive
      decline. As a main result, we demonstrate that 40 h of golf practice, performed
      as a leisure activity with highly individual training protocols, are associated
      with gray matter increases in a task-relevant cortical network encompassing
      sensorimotor regions and areas belonging to the dorsal stream. A new and striking
      result is the relationship between training intensity (time needed to complete
      the 40 training hours) and structural changes observed in the parieto-occipital
      junction. Thus, we demonstrate that a physical leisure activity induces training
      dependent changes in gray matter and assume that a strict and controlled training
      protocol is not mandatory for training-induced adaptations of gray matter.

PMID- 21880906
TI  - Platelet-derived growth factor B chain is a novel target gene of cocaine-mediated
      Notch1 signaling: implications for HIV-associated neurological disorders.
AB  - Neuroinflammation associated with HIV-1 infection is exacerbated in cocaine
      abusing, HIV+ individuals. The underlying mechanisms are, in part, attributable
      to disruption of the blood-brain barrier modulated by cocaine via platelet
      derived growth factor B chain (PDGF-B). Since Notch signaling plays a critical
      role in CNS homeostasis, we hypothesized that it may have a role in cocaine
      mediated induction of PDGF-B. The goal of this study was to link Notch signaling
      with PDGF-B. Using Western blot analysis, we demonstrate the role of Notch1
      signaling in cocaine-mediated induction of PDGF-B in human brain microvascular
      endothelial cells. Exposure of cells to the gamma-secretase inhibitor-DAPT or
      silencing of Notch1 resulted in abrogation of cocaine-mediated induction of PDGF
      B. Reciprocally, activation of the Notch1 receptor by exposing cells to the Notch
      ligand Jagged-1 resulted in upregulation of PDGF-B expression. Furthermore, it
      was demonstrated that cocaine-mediated activation of Notch1 signaling leading to
      targeted expression of PDGF-B involved activation of the downstream effector CSL.
      Functional implication of Notch1 signaling in regulating expression of the
      vascular permeant PDGF-B was confirmed in vitro using cell permeability assays.
      In vivo relevance was further corroborated in cocaine-treated mice that
      demonstrated increased permeability of the endothelial barrier as evidenced by
      Evans blue and sodium fluorescein extravasation. Specificity of Notch1 signaling
      in vivo was validated in mice exposed to DAPT, which failed to demonstrate
      barrier disruption following cocaine exposure. This is the first evidence of
      involvement of Notch1 activation in cocaine-mediated regulation of PDGF-B
      expression.

PMID- 21880907
TI  - Involvement of newborn neurons in olfactory associative learning? The operant or
      non-operant component of the task makes all the difference.
AB  - New neurons are continuously generated in the adult mammalian olfactory bulb. The
      role of these newborn neurons in olfactory learning has been debated. Blocking
      the addition of neurons has been reported either to result in memory alteration
      or to have no effect at all (Imayoshi et al., 2008; Breton-Provencher et al.,
      2009; Lazarini et al., 2009; Sultan et al., 2010). These discrepancies may have
      arisen from differences in the behavioral paradigms used: operant procedures
      indicated that neurogenesis blockade had substantial effects on long-term memory
      (Lazarini et al., 2009; Sultan et al., 2010) whereas other methods had little
      effect (Imayoshi et al., 2008; Breton-Provencher et al., 2009). Surprisingly,
      while operant learning is known to modulate the survival of new neurons, the
      effect of non-operant learning on newborn cells is unknown. Here we use mice to
      show that compared with operant learning, non-operant learning does not affect
      cell survival, perhaps explaining the current controversy. In addition, we
      provide evidence that distinct neural substrates at least partly underlie these
      two forms of learning. We conclude that the involvement of newborn neurons in
      learning is subtly dependent on the nature of the behavioral task.

PMID- 21880908
TI  - Age-related changes in orienting attention in time.
AB  - Temporal cues guide attentional resources toward relevant points in time,
      resulting in optimized behavioral performance. Although deficits in aspects of
      attention have been documented in older adults, it remains unknown whether the
      critical ability to orient attention in time is affected by normal aging. To
      address this, younger and older adults participated in a temporally cued target
      response experiment while electroencephalographic data were recorded. Three
      conditions (one detection and two discrimination tasks) were used to manipulate
      task complexity. Response times show that younger adults, but not older adults,
      used temporal cues to enhance performance regardless of task complexity.
      Similarly, alpha band activity (8-12 Hz) and the contingent negative variation
      preceding targets indicated that only younger adults engaged prestimulus,
      anticipatory neural mechanisms associated with temporal cues. Overall, these
      results provide novel evidence that older adults do not use temporal cues to
      orient attention in time and support an expectation deficit in normal aging.

PMID- 21880909
TI  - Genetic deletion of cdc42 reveals a crucial role for astrocyte recruitment to the
      injury site in vitro and in vivo.
AB  - It is generally suggested that astrocytes play important restorative functions
      after brain injury, yet little is known regarding their recruitment to sites of
      injury, despite numerous in vitro experiments investigating astrocyte polarity.
      Here, we genetically manipulated one of the proposed key signals, the small
      RhoGTPase Cdc42, selectively in mouse astrocytes in vitro and in vivo. We used an
      in vitro scratch assay as a minimal wounding model and found that astrocytes
      lacking Cdc42 (Cdc42Delta) were still able to form protrusions, although in a
      nonoriented way. Consequently, they failed to migrate in a directed manner toward
      the scratch. When animals were injured in vivo through a stab wound, Cdc42Delta
      astrocytes developed protrusions properly oriented toward the lesion, but the
      number of astrocytes recruited to the lesion site was significantly reduced.
      Surprisingly, however, lesions in Cdc42Delta animals, harboring fewer astrocytes
      contained significantly higher numbers of microglial cells than controls. These
      data suggest that impaired recruitment of astrocytes to sites of injury has a
      profound and unexpected effect on microglia recruitment.

PMID- 21880910
TI  - Neuronal production of transthyretin in human and murine Alzheimer's disease: is
      it protective?
AB  - Transthyretin (TTR), a systemic amyloid precursor in the human TTR amyloidoses,
      interacts with beta-amyloid (Abeta) in vitro, inhibits Abeta fibril formation,
      and suppresses the Alzheimer's disease (AD) phenotype in APP23 mice bearing a
      human APP gene containing the Swedish autosomal dominant AD mutation. In the
      present study, we show that TTR is a neuronal product upregulated in AD.
      Immunohistochemical analysis reveals that, in contrast to brains from non
      demented age-matched individuals and control mice, the majority of hippocampal
      neurons from human AD and all those from the APP23 mouse brains contain TTR.
      Quantitative PCR for TTR mRNA and Western blot analysis show that primary neurons
      from APP23 mice transcribe TTR mRNA, and the cells synthesize and secrete TTR
      protein. TTR mRNA abundance is greatly increased in cultured cortical and
      hippocampal embryonic neurons and cortical lysates from adult APP23 mice.
      Antibodies specific for TTR and Abeta pulled down TTR/Abeta complexes from
      cerebral cortical extracts of APP23 mice and some human AD patients but not from
      control brains. In complementary tissue culture experiments, recombinant human
      TTR suppressed the cytotoxicity of soluble Abeta aggregates added to mouse
      neurons and differentiated human SH-SY5Y neuroblastoma cells. The findings that
      production of Abeta, its precursor, or its related peptides induces neuronal TTR
      transcription and synthesis and the presence of Abeta/TTR complexes in vivo
      suggest that increased TTR production coupled with interaction between TTR and
      Abeta and/or its related peptides may play a role in natural resistance to human
      AD.

PMID- 21880912
TI  - Saccadic inhibition reveals the timing of automatic and voluntary signals in the
      human brain.
AB  - Neurophysiological and phenomenological data on sensorimotor decision making are
      growing so rapidly that it is now necessary and achievable to capture it in
      biologically inspired models, for advancing our understanding in both research
      and clinical settings. However, the main impediment in moving from elegant models
      with few free parameters to more complex biological models in humans lies in
      constraining the more numerous parameters with behavioral data (without human
      single-cell recording). Here we show that a behavioral effect called "saccadic
      inhibition" (1) is predicted by existing complex (neuronal field) models, (2)
      constrains crucial temporal parameters of the model, precisely enough to address
      individual differences, and (3) is not accounted for by current simple decision
      models, even after significant additions. Visual onsets appearing while an
      observer plans a saccade knock out a subpopulation of saccadic latencies that
      would otherwise occur, producing a clear dip in the latency distribution. This
      overlooked phenomenon is remarkably well time locked across conditions and
      observers, revealing and characterizing a fast automatic component of visual
      input to oculomotor competition. The neural field model not only captures this
      but predicts additional features that are borne out: the dips show spatial
      specificity, are lawfully modulated in contrast, and occur with S-cone stimuli
      invisible to the retinotectal route. Overall, we provide a way forward for
      applying precise neurophysiological models of saccade planning in humans at the
      individual level.

PMID- 21880911
TI  - Corticotropin-releasing factor receptor 1 antagonist alters regional activation
      and effective connectivity in an emotional-arousal circuit during expectation of
      abdominal pain.
AB  - Alterations in corticotropin-releasing factor (CRF) signaling pathways have been
      implicated in irritable bowel syndrome (IBS) pathophysiology. We aimed to (1)
      determine the effect of the selective CRF receptor 1 antagonist (CRF(1)) GW876008
      relative to placebo, on regional activation and effective connectivity of a
      stress-related emotional-arousal circuit during expectation of abdominal pain
      using functional magnetic resonance imaging in human subjects with a diagnosis of
      IBS and healthy controls (HCs), and (2) examine GW876008 effects on state-trait
      anxiety and hypothalamic-pituitary-adrenal (HPA) axis response. Although there
      were no drug-related effects on peripheral HPA activity, significant central
      effects were observed in brain regions associated with the stress response.
      Effective connectivity analysis showed drug-induced normalizations between key
      regions of the emotional-arousal circuit in patients. During pain expectation,
      orally administered GW876008 relative to placebo produced significant blood
      oxygen level-dependent (BOLD) signal reductions in the amygdala, hippocampus,
      insula, anterior cingulate, and orbitomedial prefrontal cortices across groups.
      Patients showed significantly greater BOLD responses in the left locus coeruleus
      and hypothalamus after placebo compared with HCs, and BOLD signal decreases in
      the left hypothalamus after drug. The inhibitory effects of GW876008 in the
      hypothalamus in patients were moderated by anxiety; patients having average and
      high levels of state anxiety showed drug-related BOLD decreases. GW876008
      represents a novel tool for elucidating the neuronal mechanisms and circuitry
      underlying hyperactivation of CRF/CRF(1) signaling and its role in IBS
      pathophysiology. The unique state anxiety effects observed suggest a potential
      pathway for therapeutic benefit of CRF(1) receptor antagonism for patients with
      stress-sensitive disorders.

PMID- 21880913
TI  - Dopamine-dependent long-term depression is expressed in striatal spiny neurons of
      both direct and indirect pathways: implications for Parkinson's disease.
AB  - Striatal medium spiny neurons (MSNs) are divided into two subpopulations exerting
      distinct effects on motor behavior. Transgenic mice carrying bacterial artificial
      chromosome (BAC) able to confer cell type-specific expression of enhanced green
      fluorescent protein (eGFP) for dopamine (DA) receptors have been developed to
      characterize differences between these subpopulations. Analysis of these mice, in
      contrast with original pioneering studies, showed that striatal long-term
      depression (LTD) was expressed in indirect but not in the direct pathway MSNs. To
      address this mismatch, we applied a new approach using combined BAC technology
      and receptor immunohistochemistry. We demonstrate that, in physiological
      conditions, DA-dependent LTD is expressed in both pathways showing that the lack
      of synaptic plasticity found in D(1) eGFP mice is associated to behavioral
      deficits. Our findings suggest caution in the use of this tool and indicate that
      the "striatal segregation" hypothesis might not explain all synaptic dysfunctions
      in Parkinson's disease.

PMID- 21880914
TI  - Compartmentalization of the GABAB receptor signaling complex is required for
      presynaptic inhibition at hippocampal synapses.
AB  - Presynaptic inhibition via G-protein-coupled receptors (GPCRs) and voltage-gated
      Ca(2+) channels constitutes a widespread regulatory mechanism of synaptic
      strength. Yet, the mechanism of intermolecular coupling underlying GPCR-mediated
      signaling at central synapses remains unresolved. Using FRET spectroscopy, we
      provide evidence for formation of spatially restricted (<100 A) complexes between
      GABA(B) receptors composed of GB(1a)/GB(2) subunits, Galpha(o)beta(1)gamma(2) G
      protein heterotrimer, and Ca(V)2.2 channels in hippocampal boutons. GABA release
      was not required for the assembly but for structural reorganization of the
      precoupled complex. Unexpectedly, GB(1a) deletion disrupted intermolecular
      associations within the complex. The GB(1a) proximal C-terminal domain was
      essential for association of the receptor, Ca(V)2.2 and Gbetagamma, but was
      dispensable for agonist-induced receptor activation and cAMP inhibition.
      Functionally, boutons lacking this complex-formation domain displayed impaired
      presynaptic inhibition of Ca(2+) transients and synaptic vesicle release. Thus,
      compartmentalization of the GABA(B1a) receptor, Gbetagamma, and Ca(V)2.2 channel
      in a signaling complex is required for presynaptic inhibition at hippocampal
      synapses.

PMID- 21880915
TI  - Functional recovery after peripheral nerve injury is dependent on the pro
      inflammatory cytokines IL-1beta and TNF: implications for neuropathic pain.
AB  - IL-1beta and TNF are potential targets in the management of neuropathic pain
      after injury. However, the importance of the IL-1 and TNF systems for peripheral
      nerve regeneration and the mechanisms by which these cytokines mediate effects
      are to be fully elucidated. Here, we demonstrate that mRNA and protein levels of
      IL-1beta and TNF are rapidly upregulated in the injured mouse sciatic nerve. Mice
      lacking both IL-1beta and TNF, or both IL-1 type 1 receptor (IL-1R1) and TNF type
      1 receptor (TNFR1), showed reduced nociceptive sensitivity (mechanical allodynia)
      compared with wild-type littermates after injury. Microinjecting recombinant IL
      1beta or TNF at the site of sciatic nerve injury in IL-1beta- and TNF-knock-out
      mice restored mechanical pain thresholds back to levels observed in injured wild
      type mice. Importantly, recovery of sciatic nerve function was impaired in IL
      1beta-, TNF-, and IL-1beta/TNF-knock-out mice. Notably, the infiltration of
      neutrophils was almost completely prevented in the sciatic nerve distal stump of
      mice lacking both IL-1R1 and TNFR1. Systemic treatment of mice with an anti-Ly6G
      antibody to deplete neutrophils, cells that play an essential role in the genesis
      of neuropathic pain, did not affect recovery of neurological function and
      peripheral axon regeneration. Together, these results suggest that targeting
      specific IL-1beta/TNF-dependent responses, such as neutrophil infiltration, is a
      better therapeutic strategy for treatment of neuropathic pain after peripheral
      nerve injury than complete blockage of cytokine production.

PMID- 21880916
TI  - Accelerated age-related cognitive decline and neurodegeneration, caused by
      deficient DNA repair.
AB  - Age-related cognitive decline and neurodegenerative diseases are a growing
      challenge for our societies with their aging populations. Accumulation of DNA
      damage has been proposed to contribute to these impairments, but direct proof
      that DNA damage results in impaired neuronal plasticity and memory is lacking.
      Here we take advantage of Ercc1(Delta/-) mutant mice, which are impaired in DNA
      nucleotide excision repair, interstrand crosslink repair, and double-strand break
      repair. We show that these mice exhibit an age-dependent decrease in neuronal
      plasticity and progressive neuronal pathology, suggestive of neurodegenerative
      processes. A similar phenotype is observed in mice where the mutation is
      restricted to excitatory forebrain neurons. Moreover, these neuron-specific
      mutants develop a learning impairment. Together, these results suggest a causal
      relationship between unrepaired, accumulating DNA damage, and age-dependent
      cognitive decline and neurodegeneration. Hence, accumulated DNA damage could
      therefore be an important factor in the onset and progression of age-related
      cognitive decline and neurodegenerative diseases.

PMID- 21880917
TI  - Kalirin binds the NR2B subunit of the NMDA receptor, altering its synaptic
      localization and function.
AB  - The ability of dendritic spines to change size and shape rapidly is critical in
      modulating synaptic strength; these morphological changes are dependent upon
      rearrangements of the actin cytoskeleton. Kalirin-7 (Kal7), a Rho guanine
      nucleotide exchange factor localized to the postsynaptic density (PSD), modulates
      dendritic spine morphology in vitro and in vivo. Kal7 activates Rac and interacts
      with several PSD proteins, including PSD-95, DISC-1, AF-6, and Arf6. Mice
      genetically lacking Kal7 (Kal7(KO)) exhibit deficient hippocampal long-term
      potentiation (LTP) as well as behavioral abnormalities in models of addiction and
      learning. Purified PSDs from Kal7(KO) mice contain diminished levels of NR2B, an
      NMDA receptor subunit that plays a critical role in LTP induction. Here we
      demonstrate that Kal7(KO) animals have decreased levels of NR2B-dependent NMDA
      receptor currents in cortical pyramidal neurons as well as a specific deficit in
      cell surface expression of NR2B. Additionally, we demonstrate that the genotypic
      differences in conditioned place preference and passive avoidance learning seen
      in Kal7(KO) mice are abrogated when animals are treated with an NR2B-specific
      antagonist during conditioning. Finally, we identify a stable interaction between
      the pleckstrin homology domain of Kal7 and the juxtamembrane region of NR2B
      preceding its cytosolic C-terminal domain. Binding of NR2B to a protein that
      modulates the actin cytoskeleton is important, as NMDA receptors require actin
      integrity for synaptic localization and function. These studies demonstrate a
      novel and functionally important interaction between the NR2B subunit of the NMDA
      receptor and Kalirin, proteins known to be essential for normal synaptic
      plasticity.

PMID- 21880918
TI  - Sound rhythms are encoded by postinhibitory rebound spiking in the superior
      paraolivary nucleus.
AB  - The superior paraolivary nucleus (SPON) is a prominent structure in the auditory
      brainstem. In contrast to the principal superior olivary nuclei with identified
      roles in processing binaural sound localization cues, the role of the SPON in
      hearing is not well understood. A combined in vitro and in vivo approach was used
      to investigate the cellular properties of SPON neurons in the mouse. Patch-clamp
      recordings in brain slices revealed that brief and well timed postinhibitory
      rebound spiking, generated by the interaction of two subthreshold-activated ion
      currents, is a hallmark of SPON neurons. The I(h) current determines the timing
      of the rebound, whereas the T-type Ca(2+) current boosts the rebound to spike
      threshold. This precisely timed rebound spiking provides a physiological
      explanation for the sensitivity of SPON neurons to sinusoidally amplitude
      modulated (SAM) tones in vivo, where peaks in the sound envelope drive inhibitory
      inputs and SPON neurons fire action potentials during the waveform troughs.
      Consistent with this notion, SPON neurons display intrinsic tuning to frequency
      modulated sinusoidal currents (1-15Hz) in vitro and discharge with strong
      synchrony to SAMs with modulation frequencies between 1 and 20 Hz in vivo. The
      results of this study suggest that the SPON is particularly well suited to encode
      rhythmic sound patterns. Such temporal periodicity information is likely
      important for detection of communication cues, such as the acoustic envelopes of
      animal vocalizations and speech signals.

PMID- 21880919
TI  - The atypical Guanine-nucleotide exchange factor, dock7, negatively regulates
      schwann cell differentiation and myelination.
AB  - In development of the peripheral nervous system, Schwann cells proliferate,
      migrate, and ultimately differentiate to form myelin sheath. In all of the
      myelination stages, Schwann cells continuously undergo morphological changes;
      however, little is known about their underlying molecular mechanisms. We
      previously cloned the dock7 gene encoding the atypical Rho family guanine
      nucleotide exchange factor (GEF) and reported the positive role of Dock7, the
      target Rho GTPases Rac/Cdc42, and the downstream c-Jun N-terminal kinase in
      Schwann cell migration (Yamauchi et al., 2008). We investigated the role of Dock7
      in Schwann cell differentiation and myelination. Knockdown of Dock7 by the
      specific small interfering (si)RNA in primary Schwann cells promotes dibutyryl
      cAMP-induced morphological differentiation, indicating the negative role of Dock7
      in Schwann cell differentiation. It also results in a shorter duration of
      activation of Rac/Cdc42 and JNK, which is the negative regulator of myelination,
      and the earlier activation of Rho and Rho-kinase, which is the positive regulator
      of myelination. To obtain the in vivo evidence, we generated Dock7 short hairpin
      (sh)RNA transgenic mice. They exhibited a decreased expression of Dock7 in the
      sciatic nerves and enhanced myelin thickness, consistent with in vitro
      observation. The effects of the in vivo knockdown on the signals to Rho GTPases
      are similar to those of the in vitro knockdown. Collectively, the signaling
      through Dock7 negatively regulates Schwann cell differentiation and the onset of
      myelination, demonstrating the unexpected role of Dock7 in the interplay between
      Schwann cell migration and myelination.

PMID- 21880920
TI  - Enhanced sucrose and cocaine self-administration and cue-induced drug seeking
      after loss of VGLUT2 in midbrain dopamine neurons in mice.
AB  - The mesostriatal dopamine (DA) system contributes to several aspects of responses
      to rewarding substances and is implicated in conditions such as drug addiction
      and eating disorders. A subset of DA neurons has been shown to express the type 2
      Vesicular glutamate transporter (Vglut2) and may therefore corelease glutamate.
      In the present study, we analyzed mice with a conditional deletion of Vglut2 in
      DA neurons (Vglut2(f/f;DAT-Cre)) to address the functional significance of the
      glutamate-DA cophenotype for responses to cocaine and food reinforcement.
      Biochemical parameters of striatal DA function were also examined by using DA
      receptor autoradiography, immediate-early gene quantitative in situ hybridization
      after cocaine challenge, and DA-selective in vivo chronoamperometry. Mice in
      which Vglut2 expression had been abrogated in DA neurons displayed enhanced
      operant self-administration of both high-sucrose food and intravenous cocaine.
      Furthermore, cocaine seeking maintained by drug-paired cues was increased by 76%,
      showing that reward-dependent plasticity is perturbed in these mice. In addition,
      several lines of evidence suggest that adaptive changes occurred in both the
      ventral and dorsal striatum in the absence of VGLUT2: DA receptor binding was
      increased, and basal mRNA levels of the DA-induced early genes Nur77 and c-fos
      were elevated as after cocaine induction. Furthermore, in vivo challenge of the
      DA system by potassium-evoked depolarization revealed less DA release in both
      striatal areas. This study demonstrates that absence of VGLUT2 in DA neurons
      leads to perturbations of reward consumption as well as reward-associated memory,
      features of particular relevance for addictive-like behavior.

PMID- 21880921
TI  - Neural basis of adaptive response time adjustment during saccade countermanding.
AB  - Humans and macaque monkeys adjust their response time adaptively in stop-signal
      (countermanding) tasks, responding slower after stop-signal trials than after
      control trials with no stop signal. We investigated the neural mechanism
      underlying this adaptive response time adjustment in macaque monkeys performing a
      saccade countermanding task. Earlier research showed that movements are initiated
      when the random accumulation of presaccadic movement-related activity reaches a
      fixed threshold. We found that a systematic delay in response time after stop
      signal trials was accomplished not through a change of threshold, baseline, or
      accumulation rate, but instead through a change in the time when activity first
      began to accumulate. The neurons underlying movement initiation have been
      identified with stochastic accumulator models of response time performance.
      Therefore, this new result provides surprising new insights into the neural
      instantiation of stochastic accumulator models and the mechanisms through which
      executive control can be exerted.

PMID- 21880922
TI  - Dissociable effects of top-down and bottom-up attention during episodic encoding.
AB  - It is well established that the formation of memories for life's experiences
      episodic memory-is influenced by how we attend to those experiences, yet the
      neural mechanisms by which attention shapes episodic encoding are still unclear.
      We investigated how top-down and bottom-up attention contribute to memory
      encoding of visual objects in humans by manipulating both types of attention
      during fMRI of episodic memory formation. We show that dorsal parietal cortex
      specifically, intraparietal sulcus (IPS)-was engaged during top-down attention
      and was also recruited during the successful formation of episodic memories. By
      contrast, bottom-up attention engaged ventral parietal cortex-specifically,
      temporoparietal junction (TPJ)-and was also more active during encoding failure.
      Functional connectivity analyses revealed further dissociations in how top-down
      and bottom-up attention influenced encoding: while both IPS and TPJ influenced
      activity in perceptual cortices thought to represent the information being
      encoded (fusiform/lateral occipital cortex), they each exerted opposite effects
      on memory encoding. Specifically, during a preparatory period preceding stimulus
      presentation, a stronger drive from IPS was associated with a higher likelihood
      that the subsequently attended stimulus would be encoded. By contrast, during
      stimulus processing, stronger connectivity with TPJ was associated with a lower
      likelihood the stimulus would be successfully encoded. These findings suggest
      that during encoding of visual objects into episodic memory, top-down and bottom
      up attention can have opposite influences on perceptual areas that subserve
      visual object representation, suggesting that one manner in which attention
      modulates memory is by altering the perceptual processing of to-be-encoded
      stimuli.

PMID- 21880923
TI  - Loss of Mecp2 in substantia nigra dopamine neurons compromises the nigrostriatal
      pathway.
AB  - Mutations in the methyl-CpG-binding protein 2 (MeCP2) result in Rett syndrome
      (RTT), an X-linked disorder that disrupts neurodevelopment. Girls with RTT
      exhibit motor deficits similar to those in Parkinson's disease, suggesting
      defects in the nigrostriatal pathway. This study examined age-dependent changes
      in dopamine neurons of the substantia nigra (SN) from wild-type, presymptomatic,
      and symptomatic Mecp2(+/-) mice. Mecp2(+) neurons in the SN in Mecp2(+/-) mice
      were indistinguishable in morphology, resting conductance, and dopamine current
      density from neurons in wild-type mice. However, the capacitance, total dendritic
      length, and resting conductance of Mecp2(-) neurons were less than those of
      Mecp2(+) neurons as early as 4 weeks after birth, before overt symptoms. These
      differences were maintained throughout life. In symptomatic Mecp2(+/-) mice, the
      current induced by activation of D(2) dopamine autoreceptors was significantly
      less in Mecp2(-) neurons than in Mecp2(+) neurons, although D(2) receptor density
      was unaltered in Mecp2(+/-) mice. Electrochemical measurements revealed that
      significantly less dopamine was released after stimulation of striatum in adult
      Mecp2(+/-) mice compared to wild type. The decrease in size and function of
      Mecp2(-) neurons observed in adult Mecp2(+/-) mice was recapitulated in dopamine
      neurons from symptomatic Mecp2(-/y) males. These results show that mutation in
      Mecp2 results in cell-autonomous defects in the SN early in life and throughout
      adulthood. Ultimately, dysfunction in terminal dopamine release and D(2)
      autoreceptor-dependent currents in dopamine neurons from symptomatic females
      support the idea that decreased dopamine transmission due to heterogeneous Mecp2
      expression contributes to the parkinsonian features of RTT in Mecp2(+/-) mice.

PMID- 21880924
TI  - Hearing loss in older adults affects neural systems supporting speech
      comprehension.
AB  - Hearing loss is one of the most common complaints in adults over the age of 60
      and a major contributor to difficulties in speech comprehension. To examine the
      effects of hearing ability on the neural processes supporting spoken language
      processing in humans, we used functional magnetic resonance imaging to monitor
      brain activity while older adults with age-normal hearing listened to sentences
      that varied in their linguistic demands. Individual differences in hearing
      ability predicted the degree of language-driven neural recruitment during
      auditory sentence comprehension in bilateral superior temporal gyri (including
      primary auditory cortex), thalamus, and brainstem. In a second experiment, we
      examined the relationship of hearing ability to cortical structural integrity
      using voxel-based morphometry, demonstrating a significant linear relationship
      between hearing ability and gray matter volume in primary auditory cortex.
      Together, these results suggest that even moderate declines in peripheral
      auditory acuity lead to a systematic downregulation of neural activity during the
      processing of higher-level aspects of speech, and may also contribute to loss of
      gray matter volume in primary auditory cortex. More generally, these findings
      support a resource-allocation framework in which individual differences in
      sensory ability help define the degree to which brain regions are recruited in
      service of a particular task.

PMID- 21880925
TI  - Distinct mechanisms for size tuning in primate visual cortex.
AB  - Most neurons in primary visual cortex (V1) are selective for stimulus size, a
      property with important implications for salient feature detection. Size
      selectivity involves dynamic interactions between neuronal circuits that
      establish the classical (center) and extraclassical (surround) of a neuron's
      receptive field. Although much is known about the tuning properties and stimulus
      selectivity of the center and surround subunits, relatively little is known about
      how these subunits interact to achieve size selectivity. To address this
      question, we examined the temporal dynamics of size selectivity in two classes of
      pyramidal neurons at similar hierarchical processing stages in V1 of alert
      monkeys. These two classes were comprised of neurons in cortical layer 6 with
      identified projections to the lateral geniculate nucleus. While both neuronal
      groups displayed comparable levels of size selectivity, the temporal dynamics of
      their tuning differed significantly. We compared the size tuning profiles of each
      cell type with a series of sum-of-Gaussian models and discovered that the
      receptive fields of neurons with fast-conducting axons contained an excitatory
      center and a suppressive surround with similar onset timing. In contrast, neurons
      with slow-conducting axons used two center components-an early wide-field
      component and a delayed narrow-field component that increased activity-in
      addition to the surround component. The early, wide-field component represents a
      novel mechanism for cortical neurons to integrate contextual information. These
      results demonstrate that size tuning in cortical neurons is established via
      multiple unique mechanisms, dictated by the rich circuit architecture in which
      neurons are embedded.

PMID- 21880926
TI  - NMDA receptor signaling in oligodendrocyte progenitors is not required for
      oligodendrogenesis and myelination.
AB  - Oligodendrocyte precursor cells (OPCs) express NMDA receptors (NMDARs) and form
      synapses with glutamatergic neurons throughout the CNS. Although glutamate
      influences the proliferation and maturation of these progenitors in vitro, the
      role of NMDAR signaling in oligodendrogenesis and myelination in vivo is not
      known. Here, we investigated the consequences of genetically deleting the
      obligatory NMDAR subunit NR1 from OPCs and their oligodendrocyte progeny in the
      CNS of developing and mature mice. NMDAR-deficient OPCs proliferated normally,
      achieved appropriate densities in gray and white matter, and differentiated to
      form major white matter tracts without delay. OPCs also retained their
      characteristic physiological and morphological properties in the absence of NMDAR
      signaling and were able to form synapses with glutamatergic axons. However,
      expression of calcium-permeable AMPA receptors (AMPARs) was enhanced in NMDAR
      deficient OPCs. These results suggest that NMDAR signaling is not used to control
      OPC development but to regulate AMPAR-dependent signaling with surrounding axons,
      pointing to additional functions for these ubiquitous glial cells.

PMID- 21880927
TI  - Overexpression of neurotrophin-3 stimulates a second wave of dopaminergic
      amacrine cell genesis after birth in the mouse retina.
AB  - Dopaminergic amacrine (DA) cells play multiple and important roles in retinal
      function. Neurotrophins are known to modulate the number and morphology of DA
      cells, but the underlying regulatory mechanisms are unclear. Here, we investigate
      how neurotrophin-3 (NT-3) regulates DA cell density in the mouse retina. We
      demonstrate that overexpression of NT-3 upregulates DA cell number and leads to a
      consequent increase in the density of DA cell dendrites. To examine the
      mechanisms of DA cell density increase, we further investigate the effect of NT-3
      overexpression on retinal apoptosis and mitosis during development. We find that
      NT-3 does not affect the well known wave of retinal cell apoptosis that normally
      occurs during the first 2 weeks after birth. Instead, overexpression of NT-3
      promotes additional mitosis of DA cells at postnatal day 4, but does not affect
      cell mitosis before birth, the peak period of amacrine cell genesis in wild-type
      retinas. We next show that retinal explants cultured from birth to day 7 without
      extra NT-3 produced by lens exhibit similar number of DA cells as in wild type,
      further supporting the notion that postnatal overexpression of lens-derived NT-3
      affects DA cell number. Moreover, the additional mitosis after birth in NT-3
      overexpressing mice does not occur in calretinin-positive amacrine cells or PKC
      positive rod ON bipolar cells. Thus, the NT-3-triggered wave of cell mitosis
      after birth is specific for the retinal DA cells.

PMID- 21880928
TI  - Network rhythms influence the relationship between spike-triggered local field
      potential and functional connectivity.
AB  - Characterizing the functional connectivity between neurons is key for
      understanding brain function. We recorded spikes and local field potentials
      (LFPs) from multielectrode arrays implanted in monkey visual cortex to test the
      hypotheses that spikes generated outward-traveling LFP waves and the strength of
      functional connectivity depended on stimulus contrast, as described recently.
      These hypotheses were proposed based on the observation that the latency of the
      peak negativity of the spike-triggered LFP average (STA) increased with distance
      between the spike and LFP electrodes, and the magnitude of the STA negativity and
      the distance over which it was observed decreased with increasing stimulus
      contrast. Detailed analysis of the shape of the STA, however, revealed
      contributions from two distinct sources-a transient negativity in the LFP locked
      to the spike (~0 ms) that attenuated rapidly with distance, and a low-frequency
      rhythm with peak negativity ~25 ms after the spike that attenuated slowly with
      distance. The overall negative peak of the LFP, which combined both these
      components, shifted from ~0 to ~25 ms going from electrodes near the spike to
      electrodes far from the spike, giving an impression of a traveling wave, although
      the shift was fully explained by changing contributions from the two fixed
      components. The low-frequency rhythm was attenuated during stimulus
      presentations, decreasing the overall magnitude of the STA. These results
      highlight the importance of accounting for the network activity while using STAs
      to determine functional connectivity.

PMID- 21880929
TI  - Frequency of subthreshold oscillations at different membrane potential voltages
      in neurons at different anatomical positions on the dorsoventral axis in the rat
      medial entorhinal cortex.
AB  - Neurons from layer II of the medial entorhinal cortex show subthreshold membrane
      potential oscillations (SMPOs) which could contribute to theta-rhythm generation
      in the entorhinal cortex and to generation of grid cell firing patterns. However,
      it is unclear whether single neurons have a fixed unique oscillation frequency or
      whether their frequency varies depending on the mean membrane potential in a
      cell. We therefore examined the frequency of SMPOs at different membrane
      potentials in layer II stellate-like cells of the rat medial entorhinal cortex in
      vitro. Using whole-cell patch recordings, we found that the fluctuations in
      membrane potential show a broad band of low power frequencies near resting
      potential that transition to more narrowband oscillation frequencies with
      depolarization. The transition from broadband to narrowband frequencies depends
      on the location of the neuron along the dorsoventral axis in the entorhinal
      cortex, with dorsal neurons transitioning to higher-frequency oscillations
      relative to ventral neurons transitioning to lower-frequency oscillations. Once
      SMPOs showed a narrowband frequency, systematic frequency changes were not
      observed with further depolarization. Using a Hodgkin-Huxley-style model of
      membrane currents, we show that differences in the influence of depolarization on
      the frequency of SMPOs at different dorsal to ventral positions could arise from
      differences in the properties of the h current. The properties of frequency
      changes in this data are important for evaluating models of the generation of
      grid cell firing fields with different spacings along the dorsal-to-ventral axis
      of medial entorhinal cortex.

PMID- 21880930
TI  - The DEG/ENaC protein MEC-10 regulates the transduction channel complex in
      Caenorhabditis elegans touch receptor neurons.
AB  - Gentle touch sensation in Caenorhabditis elegans is mediated by the MEC-4/MEC-10
      channel complex, which is expressed exclusively in six touch receptor neurons
      (TRNs). The complex contains two pore-forming subunits, MEC-4 and MEC-10, as well
      as the accessory subunits MEC-2, MEC-6, and UNC-24. MEC-4 is essential for
      channel function, but beyond its role as a pore-forming subunit, the functional
      contribution of MEC-10 to the channel complex and to touch sensation is unclear.
      We addressed this question using behavioral assays, in vivo electrophysiological
      recordings from TRNs, and heterologous expression of mutant MEC-10 isoforms.
      Animals with a deletion in mec-10 showed only a partial loss of touch sensitivity
      and a modest decrease in the size of the mechanoreceptor current (MRC). In
      contrast, five previously identified mec-10 alleles acted as recessive gain-of
      function alleles that resulted in complete touch insensitivity. Each of these
      alleles produced a substantial decrease in MRC size and a shift in the reversal
      potential in vivo. The latter finding indicates that these mec-10 mutations alter
      the ionic selectivity of the transduction channel in vivo. All mec-10 mutant
      animals had properly localized channel complexes, indicating that the loss of
      MRCs was not attributable to a dramatic mislocalization of transduction channels.
      Finally, electrophysiological examination of heterologously expressed complexes
      suggests that mutant MEC-10 proteins may affect channel current via MEC-2.

PMID- 21880931
TI  - Oligogalacturonide-auxin antagonism does not require posttranscriptional gene
      silencing or stabilization of auxin response repressors in Arabidopsis.
AB  - alpha-1-4-Linked oligogalacturonides (OGs) derived from plant cell walls are a
      class of damage-associated molecular patterns and well-known elicitors of the
      plant immune response. Early transcript changes induced by OGs largely overlap
      those induced by flg22, a peptide derived from bacterial flagellin, a well
      characterized microbe-associated molecular pattern, although responses diverge
      over time. OGs also regulate growth and development of plant cells and organs,
      due to an auxin-antagonistic activity. The molecular basis of this antagonism is
      still unknown. Here we show that, in Arabidopsis (Arabidopsis thaliana), OGs
      inhibit adventitious root formation induced by auxin in leaf explants as well as
      the expression of several auxin-responsive genes. Genetic, biochemical, and
      pharmacological experiments indicate that inhibition of auxin responses by OGs
      does not require ethylene, jasmonic acid, and salicylic acid signaling and is
      independent of RESPIRATORY BURST OXIDASE HOMOLOGUE D-mediated reactive oxygen
      species production. Free indole-3-acetic acid levels are not noticeably altered
      by OGs. Notably, OG- as well as flg22-auxin antagonism does not involve any of
      the following mechanisms: (1) stabilization of auxin-response repressors; (2)
      decreased levels of auxin receptor transcripts through the action of microRNAs.
      Our results suggest that OGs and flg22 antagonize auxin responses independently
      of Aux/Indole-3-Acetic Acid repressor stabilization and of posttranscriptional
      gene silencing.

PMID- 21880932
TI  - Key proliferative activity in the junction between the leaf blade and leaf
      petiole of Arabidopsis.
AB  - Leaves are the most important, fundamental units of organogenesis in plants.
      Although the basic form of a leaf is clearly divided into the leaf blade and leaf
      petiole, no study has yet revealed how these are differentiated from a leaf
      primordium. We analyzed the spatiotemporal pattern of mitotic activity in leaf
      primordia of Arabidopsis (Arabidopsis thaliana) in detail using molecular markers
      in combination with clonal analysis. We found that the proliferative zone is
      established after a short interval following the occurrence of a rod-shaped early
      leaf primordium; it is separated spatially from the shoot apical meristem and
      seen at the junction region between the leaf blade and leaf petiole and produces
      both leaf-blade and leaf-petiole cells. This proliferative region in leaf
      primordia is marked by activity of the ANGUSTIFOLIA3 (AN3) promoter as a whole
      and seems to be differentiated into several spatial compartments: activities of
      the CYCLIN D4;2 promoter and SPATULA enhancer mark parts of it specifically.
      Detailed analyses of the an3 and blade-on-petiole mutations further support the
      idea that organogenesis of the leaf blade and leaf petiole is critically
      dependent on the correct spatial regulation of the proliferative region of leaf
      primordia. Thus, the proliferative zone of leaf primordia is spatially
      differentiated and supplies both the leaf-blade and leaf-petiole cells.

PMID- 21880933
TI  - Molecular dissection of the roles of phytochrome in photoperiodic flowering in
      rice.
AB  - Phytochromes mediate the photoperiodic control of flowering in rice (Oryza
      sativa), a short-day plant. Recent molecular genetics studies have revealed a
      genetic network that enables the critical daylength response of florigen gene
      expression. Analyses using a rice phytochrome chromophore-deficient mutant,
      photoperiod sensitivity5, have so far revealed that within this network,
      phytochromes are required for expression of Grain number, plant height and
      heading date7 (Ghd7), a floral repressor gene in rice. There are three
      phytochrome genes in rice, but the roles of each phytochrome family member in
      daylength response have not previously been defined. Here, we revealed multiple
      action points for each phytochrome in the critical daylength response of florigen
      expression by using single and double phytochrome mutant lines of rice. Our
      results show that either phyA alone or a genetic combination of phyB and phyC can
      induce Ghd7 mRNA, whereas phyB alone causes some reduction in levels of Ghd7
      mRNA. Moreover, phyB and phyA can affect Ghd7 activity and Early heading date1 (a
      floral inducer) activity in the network, respectively. Therefore, each
      phytochrome gene of rice has distinct roles, and all of the phytochrome actions
      coordinately control the critical daylength response of florigen expression in
      rice.

PMID- 21880935
TI  - Slow and fast rhythms generated in the cerebral cortex of the anesthetized mouse.
AB  - A characterization of the oscillatory activity in the cerebral cortex of the
      mouse was realized under ketamine anesthesia. Bilateral recordings were obtained
      from deep layers of primary visual, somatosensory, motor, and medial prefrontal
      cortex. A slow oscillatory activity consisting of up and down states was
      detected, the average frequency being 0.97 Hz in all areas. Different parameters
      of the oscillation were estimated across cortical areas, including duration of up
      and down states and their variability, speed of state transitions, and population
      firing rate. Similar values were obtained for all areas except for prefrontal
      cortex, which showed significant faster down-to-up state transitions, higher
      firing rate during up states, and more regular cycles. The wave propagation
      patterns in the anteroposterior axis in motor cortex and the mediolateral axis in
      visual cortex were studied with multielectrode recordings, yielding speed values
      between 8 and 93 mm/s. The firing of single units was analyzed with respect to
      the population activity. The most common pattern was that of neurons firing in
      >90% of the up states with 1-6 spikes. Finally, fast rhythms (beta, low gamma,
      and high gamma) were analyzed, all of them showing significantly larger power
      during up states than in down states. Prefrontal cortex exhibited significantly
      larger power in both beta and gamma bands (up to 1 order of magnitude larger in
      the case of high gamma) than the rest of the cortical areas. This study allows us
      to carry out interareal comparisons and provides a baseline to compare against
      cortical emerging activity from genetically altered animals.

PMID- 21880934
TI  - Release from the cone ribbon synapse under bright light conditions can be
      controlled by the opening of only a few Ca(2+) channels.
AB  - Light hyperpolarizes cone photoreceptors, causing synaptic voltage-gated Ca(2+)
      channels to open infrequently. To understand neurotransmission under these
      conditions, we determined the number of L-type Ca(2+) channel openings necessary
      for vesicle fusion at the cone ribbon synapse. Ca(2+) currents (I(Ca)) were
      activated in voltage-clamped cones, and excitatory postsynaptic currents (EPSCs)
      were recorded from horizontal cells in the salamander retina slice preparation.
      Ca(2+) channel number and single-channel current amplitude were calculated by
      mean-variance analysis of I(Ca). Two different comparisons-one comparing average
      numbers of release events to average I(Ca) amplitude and the other involving
      deconvolution of both EPSCs and simultaneously recorded cone I(Ca)-suggested that
      fewer than three Ca(2+) channel openings accompanied fusion of each vesicle at
      the peak of release during the first few milliseconds of stimulation. Opening
      fewer Ca(2+) channels did not enhance fusion efficiency, suggesting that few
      unnecessary channel openings occurred during strong depolarization. We simulated
      release at the cone synapse, using empirically determined synaptic dimensions,
      vesicle pool size, Ca(2+) dependence of release, Ca(2+) channel number, and
      Ca(2+) channel properties. The model replicated observations when a barrier was
      added to slow Ca(2+) diffusion. Consistent with the presence of a diffusion
      barrier, dialyzing cones with diffusible Ca(2+) buffers did not affect release
      efficiency. The tight clustering of Ca(2+) channels, along with a high-Ca(2+)
      affinity release mechanism and diffusion barrier, promotes a linear coupling
      between Ca(2+) influx and vesicle fusion. This may improve detection of small
      light decrements when cones are hyperpolarized by bright light.

PMID- 21880936
TI  - Taking into account latency, amplitude, and morphology: improved estimation of
      single-trial ERPs by wavelet filtering and multiple linear regression.
AB  - Across-trial averaging is a widely used approach to enhance the signal-to-noise
      ratio (SNR) of event-related potentials (ERPs). However, across-trial variability
      of ERP latency and amplitude may contain physiologically relevant information
      that is lost by across-trial averaging. Hence, we aimed to develop a novel method
      that uses 1) wavelet filtering (WF) to enhance the SNR of ERPs and 2) a multiple
      linear regression with a dispersion term (MLR(d)) that takes into account shape
      distortions to estimate the single-trial latency and amplitude of ERP peaks.
      Using simulated ERP data sets containing different levels of noise, we provide
      evidence that, compared with other approaches, the proposed WF+MLR(d) method
      yields the most accurate estimate of single-trial ERP features. When applied to a
      real laser-evoked potential data set, the WF+MLR(d) approach provides reliable
      estimation of single-trial latency, amplitude, and morphology of ERPs and thereby
      allows performing meaningful correlations at single-trial level. We obtained
      three main findings. First, WF significantly enhances the SNR of single-trial
      ERPs. Second, MLR(d) effectively captures and measures the variability in the
      morphology of single-trial ERPs, thus providing an accurate and unbiased estimate
      of their peak latency and amplitude. Third, intensity of pain perception
      significantly correlates with the single-trial estimates of N2 and P2 amplitude.
      These results indicate that WF+MLR(d) can be used to explore the dynamics between
      different ERP features, behavioral variables, and other neuroimaging measures of
      brain activity, thus providing new insights into the functional significance of
      the different brain processes underlying the brain responses to sensory stimuli.

PMID- 21880937
TI  - The ionic mechanism of gamma resonance in rat striatal fast-spiking neurons.
AB  - Striatal fast-spiking (FS) cells in slices fire in the gamma frequency range and
      in vivo are often phase-locked to gamma oscillations in the field potential. We
      studied the firing patterns of these cells in slices from rats ages 16-23 days to
      determine the mechanism of their gamma resonance. The resonance of striatal FS
      cells was manifested as a minimum frequency for repetitive firing. At rheobase,
      cells fired a doublet of action potentials or doublets separated by pauses, with
      an instantaneous firing rate averaging 44 spikes/s. The minimum rate for
      sustained firing was also responsible for the stuttering firing pattern. Firing
      rate adapted during each episode of firing, and bursts were terminated when
      firing was reduced to the minimum sustainable rate. Resonance and stuttering
      continued after blockade of Kv3 current using tetraethylammonium (0.1-1 mM). Both
      gamma resonance and stuttering were strongly dependent on Kv1 current. Blockade
      of Kv1 channels with dendrotoxin-I (100 nM) completely abolished the stuttering
      firing pattern, greatly lowered the minimum firing rate, abolished gamma-band
      subthreshold oscillations, and slowed spike frequency adaptation. The loss of
      resonance could be accounted for by a reduction in potassium current near spike
      threshold and the emergence of a fixed spike threshold. Inactivation of the Kv1
      channel combined with the minimum firing rate could account for the stuttering
      firing pattern. The resonant properties conferred by this channel were shown to
      be adequate to account for their phase-locking to gamma-frequency inputs as seen
      in vivo.

PMID- 21880939
TI  - Superposition and modulation of muscle synergies for reaching in response to a
      change in target location.
AB  - We have recently shown that the muscle patterns for reaching are well described
      by the combination of a few time-varying muscle synergies supporting the notion
      of a modular architecture for arm control. Here we investigated whether the
      muscle patterns for reaching movements involving online corrections are also
      generated by the combination of the same set of time-varying muscle synergies
      used for point-to-point movements. We recorded endpoint kinematics and EMGs from
      up to 16 arm muscles of 5 subjects reaching from a central location to 8
      peripheral targets in the frontal plane, from each peripheral target to 1 of the
      2 adjacent targets, and from the central location initially to 1 peripheral
      target and, after a delay of either 50, 150, or 250 ms from the go signal, to 1
      of the 2 adjacent targets. Time-varying muscle synergies were extracted from the
      averaged, phasic, normalized EMGs of point-to-point movements and fit to the
      patterns of target change movements using an iterative optimization algorithm. In
      all subjects, three time-varying muscle synergies explained a large fraction of
      the data variation of point-to-point movements. The superposition and modulation
      of the same three synergies reconstructed the muscle patterns for target change
      movements better than the superposition and modulation of the corresponding point
      to-point muscle patterns, appropriately aligned. While at the kinematic level the
      corrective trajectory for reaching during a change in target location can be
      obtained by the delayed superposition of the trajectory from the initial to the
      final target, at the muscle level the underlying phasic muscle patterns are
      captured by the amplitude and timing modulation of the same time-varying muscle
      synergies recruited for point-to-point movements. These results suggest that a
      common modular architecture is used for the control of unperturbed arm movement
      and for its visually guided online corrections.

PMID- 21880938
TI  - Hand kinematics of piano playing.
AB  - Dexterous use of the hand represents a sophisticated sensorimotor function. In
      behaviors such as playing the piano, it can involve strong temporal and spatial
      constraints. The purpose of this study was to determine fundamental patterns of
      covariation of motion across joints and digits of the human hand. Joint motion
      was recorded while 5 expert pianists played 30 excerpts from musical pieces,
      which featured ~50 different tone sequences and fingering. Principal component
      analysis and cluster analysis using an expectation-maximization algorithm
      revealed that joint velocities could be categorized into several patterns, which
      help to simplify the description of the movements of the multiple degrees of
      freedom of the hand. For the thumb keystroke, two distinct patterns of joint
      movement covariation emerged and they depended on the spatiotemporal patterns of
      the task. For example, the thumb-under maneuver was clearly separated into two
      clusters based on the direction of hand translation along the keyboard. While the
      pattern of the thumb joint velocities differed between these clusters, the
      motions at the metacarpo-phalangeal and proximal-phalangeal joints of the four
      fingers were more consistent. For a keystroke executed with one of the fingers,
      there were three distinct patterns of joint rotations, across which motion at the
      striking finger was fairly consistent, but motion of the other fingers was more
      variable. Furthermore, the amount of movement spillover of the striking finger to
      the adjacent fingers was small irrespective of the finger used for the keystroke.
      These findings describe an unparalleled amount of independent motion of the
      fingers.

PMID- 21880940
TI  - TMS of the right angular gyrus modulates priming of pop-out in visual search:
      combined TMS-ERP evidence.
AB  - During priming of pop-out, performance at discriminating a pop-out feature target
      in visual search is affected by whether the target on the previous trial was
      defined by the same feature as on the upcoming trial. Recent studies suggest that
      priming of pop-out relies on attentional processes. With the use of simultaneous,
      combined transcranial magnetic stimulation and event-related potential recording
      (TMS-ERP), we tested for any critical role of the right angular gyrus (rANG) and
      left and right frontal eye fields (FEFs)-key attentional sites-in modulating both
      performance and the ERPs evoked by such visual events. Intertrial TMS trains were
      applied while participants discriminated the orientation of a color pop-out
      element in a visual search array. rANG TMS disrupted priming of pop-out, reducing
      reaction time costs on switch trials and speeding responses when the color of the
      pop-out target switched. rANG TMS caused a negativity in the ERP elicited in
      response to the visual stimulus array, starting 210 ms after stimulus onset. Both
      behavioral and ERP effects were apparent only after rANG TMS, on switch trials,
      and when the target in the visual search array was presented in the left visual
      field, with no effects after left or right FEF TMS. These results provide
      evidence for an attentional reorienting mechanism, which originates in the rANG
      and is modulated by the implicit memory of the previous trial. The rANG plays a
      causal role on switch trials during priming of pop-out by interacting with visual
      processing, particularly in the ipsilateral hemisphere representing the
      contralateral hemifield.

PMID- 21880941
TI  - How reliable are the functional connectivity networks of MEG in resting states?
AB  - We investigated the reliability of nodal network metrics of functional
      connectivity (FC) networks of magnetoencephalography (MEG) covering the whole
      brain at the sensor level in the eyes-closed (EC) and eyes-open (EO) resting
      states. Mutual information (MI) was employed as a measure of FC between sensors
      in theta, alpha, beta, and gamma frequency bands of MEG signals. MI matrices were
      assessed with three nodal network metrics, i.e., nodal degree (Dnodal), nodal
      efficiency (Enodal), and betweenness centrality (normBC). Intraclass correlation
      (ICC) values were calculated as a measure of reliability. We observed that the
      test-retest reliabilities of the resting states ranged from a poor to good level
      depending on the bands and metrics used for defining the nodal centrality. The
      dominant alpha-band FC network changes were the salient features of the state
      related FC changes. The FC networks in the EO resting state showed greater
      reliability when assessed by Dnodal (maximum mean ICC = 0.655) and Enodal
      (maximum mean ICC = 0.604) metrics. The gamma-band FC network was less reliable
      than the theta, alpha, and beta networks across the nodal network metrics.
      However, the sensor-wise ICC values for the nodal centrality metrics were not
      uniformly distributed, that is, some sensors had high reliability. This study
      provides a sense of how the nodal centralities of the human resting state MEG are
      distributed at the sensor level and how reliable they are. It also provides a
      fundamental scientific background for continued examination of the resting state
      of human MEG.

PMID- 21880944
TI  - The co-occurrence of multisensory facilitation and cross-modal conflict in the
      human brain.
AB  - Perceptual objects often comprise a visual and auditory signature that arrives
      simultaneously through distinct sensory channels, and cross-modal features are
      linked by virtue of being attributed to a specific object. Continued exposure to
      cross-modal events sets up expectations about what a given object most likely
      "sounds" like, and vice versa, thereby facilitating object detection and
      recognition. The binding of familiar auditory and visual signatures is referred
      to as semantic, multisensory integration. Whereas integration of semantically
      related cross-modal features is behaviorally advantageous, situations of sensory
      dominance of one modality at the expense of another impair performance. In the
      present study, magnetoencephalography recordings of semantically related cross
      modal and unimodal stimuli captured the spatiotemporal patterns underlying
      multisensory processing at multiple stages. At early stages, 100 ms after
      stimulus onset, posterior parietal brain regions responded preferentially to
      cross-modal stimuli irrespective of task instructions or the degree of semantic
      relatedness between the auditory and visual components. As participants were
      required to classify cross-modal stimuli into semantic categories, activity in
      superior temporal and posterior cingulate cortices increased between 200 and 400
      ms. As task instructions changed to incorporate cross-modal conflict, a process
      whereby auditory and visual components of cross-modal stimuli were compared to
      estimate their degree of congruence, multisensory processes were captured in
      parahippocampal, dorsomedial, and orbitofrontal cortices 100 and 400 ms after
      stimulus onset. Our results suggest that multisensory facilitation is associated
      with posterior parietal activity as early as 100 ms after stimulus onset.
      However, as participants are required to evaluate cross-modal stimuli based on
      their semantic category or their degree of congruence, multisensory processes
      extend in cingulate, temporal, and prefrontal cortices.

PMID- 21880943
TI  - Molecular and functional differences in voltage-activated sodium currents between
      GABA projection neurons and dopamine neurons in the substantia nigra.
AB  - GABA projection neurons (GABA neurons) in the substantia nigra pars reticulata
      (SNr) and dopamine projection neurons (DA neurons) in substantia nigra pars
      compacta (SNc) have strikingly different firing properties. SNc DA neurons fire
      low-frequency, long-duration spikes, whereas SNr GABA neurons fire high
      frequency, short-duration spikes. Since voltage-activated sodium (Na(V)) channels
      are critical to spike generation, the different firing properties raise the
      possibility that, compared with DA neurons, Na(V) channels in SNr GABA neurons
      have higher density, faster kinetics, and less cumulative inactivation. Our
      quantitative RT-PCR analysis on immunohistochemically identified nigral neurons
      indicated that mRNAs for pore-forming Na(V)1.1 and Na(V)1.6 subunits and
      regulatory Na(V)beta1 and Na(v)beta4 subunits are more abundant in SNr GABA
      neurons than SNc DA neurons. These alpha-subunits and beta-subunits are key
      subunits for forming Na(V) channels conducting the transient Na(V) current
      (I(NaT)), persistent Na current (I(NaP)), and resurgent Na current (I(NaR)).
      Nucleated patch-clamp recordings showed that I(NaT) had a higher density, a
      steeper voltage-dependent activation, and a faster deactivation in SNr GABA
      neurons than in SNc DA neurons. I(NaT) also recovered more quickly from
      inactivation and had less cumulative inactivation in SNr GABA neurons than in SNc
      DA neurons. Furthermore, compared with nigral DA neurons, SNr GABA neurons had a
      larger I(NaR) and I(NaP). Blockade of I(NaP) induced a larger hyperpolarization
      in SNr GABA neurons than in SNc DA neurons. Taken together, these results
      indicate that Na(V) channels expressed in fast-spiking SNr GABA neurons and slow
      spiking SNc DA neurons are tailored to support their different spiking
      capabilities.

PMID- 21880942
TI  - Pain-related deactivation of medial prefrontal cortical neurons involves mGluR1
      and GABA(A) receptors.
AB  - Pain-related hyperactivity in the amygdala leads to deactivation of the medial
      prefrontal cortex (mPFC) and decision-making deficits. The mechanisms of pain
      related inhibition of the mPFC are not yet known. Here, we used extracellular
      single-unit recordings of prelimbic mPFC neurons to determine the role of GABA(A)
      receptors and metabotropic glutamate receptor (mGluR) subtypes, mGluR1 and
      mGluR5, in pain-related activity changes of mPFC neurons. Background and evoked
      activity of mPFC neurons decreased after arthritis induction. To determine pain
      related changes, the same neuron was recorded continuously before and after
      induction of arthritis in one knee joint by intra-articular injection of
      kaolin/carrageenan. Stereotaxic administration of a GABA(A) receptor antagonist
      {[R-(R*,S*)]-5-(6,8-dihydro-8-oxofuro[3,4-e]-1,3-benzodioxol-6-yl)-5,6,7,8
      tetrahydro-6,6-dimethyl-1,3-dioxolo[4,5-g]isoquinolinium iodide (bicuculline)}
      into the mPFC by microdialysis reversed pain-related inhibition, whereas offsite
      injections into the adjacent anterior cingulate cortex had no or opposite effects
      on prelimbic mPFC neurons. A selective mGluR1/5 agonist [(S)-3,5
      dihydroxyphenylglycine (DHPG)] inhibited background and evoked activity under
      normal conditions through a GABAergic mechanism, because the inhibitory effect
      was blocked with bicuculline. In the arthritis pain state, DHPG, alone or in the
      presence of bicuculline, had no effect. Consistent with the involvement of mGluR1
      in pain-related inhibition of the mPFC, a selective mGluR1 antagonist [(S)-(+)
      alpha-amino-4-carboxy-2-methylbenzeneacetic acid] reversed the pain-related
      decrease of background and evoked activity of mPFC neurons in arthritis, whereas
      a selective mGluR5 antagonist [2-methyl-6-(phenylethynyl)pyridine hydrochloride]
      had no effect. The mGluR antagonists had no effect under normal conditions. We
      interpret our data to suggest that pain-related inhibition of mPFC neurons in the
      arthritis model depends on mGluR1-mediated endogenous activation of GABA(A)
      receptors. Exogenous activation of mGluR1/5 produces GABAergic inhibition under
      normal conditions. Restoring normal activity in the mPFC may be a therapeutic
      strategy to improve cognitive deficits associated with persistent pain.

PMID- 21880945
TI  - Optogenetic regulation of leg movement in midstage chick embryos through
      peripheral nerve stimulation.
AB  - Numerous disorders that affect proper development, including the structure and
      function of the nervous system, are associated with altered embryonic movement.
      Ongoing challenges are to understand in detail how embryonic movement is
      generated and to understand better the connection between proper movement and
      normal nervous system function. Controlled manipulation of embryonic limb
      movement and neuronal activity to assess short- and long-term outcomes can be
      difficult. Optogenetics is a powerful new approach to modulate neuronal activity
      in vivo. In this study, we have used an optogenetics approach to activate
      peripheral motor axons and thus alter leg motility in the embryonic chick. We
      used electroporation of a transposon-based expression system to produce ChIEF, a
      channelrhodopsin-2 variant, in the lumbosacral spinal cord of chick embryos. The
      transposon-based system allows for stable incorporation of transgenes into the
      genomic DNA of recipient cells. ChIEF protein is detectable within 24 h of
      electroporation, largely membrane-localized, and found throughout embryonic
      development in both central and peripheral processes. The optical clarity of thin
      embryonic tissue allows detailed innervation patterns of ChIEF-containing motor
      axons to be visualized in the living embryo in ovo, and pulses of blue light
      delivered to the thigh can elicit stereotyped flexures of the leg when the embryo
      is at rest. Continuous illumination can disrupt full extension of the leg during
      spontaneous movements. Therefore, our results establish an optogenetics approach
      to alter normal peripheral axon function and to probe the role of movement and
      neuronal activity in sensorimotor development throughout embryogenesis.

PMID- 21880946
TI  - Repeated use of surrogate mothers for embryo transfer in the mouse.
AB  - Embryo transfer in mice is a crucial technique for generation of transgenic
      animals, rederivation of contaminated lines, and revitalization of cryopreserved
      strains, and it is a key component of assisted reproduction techniques. It is
      common practice to use females only once as surrogate mothers. However, their
      reuse for a second embryo transfer could provide hygienic and economic advantages
      and conform to the concept of the 3Rs (replace, reduce, refine). This
      investigation evaluated the potential for a second embryo transfer in terms of
      feasibility, reproductive results, and experimental burden for the animal. Virgin
      female ICR mice (age 8-16 wk) were used as recipients for the first embryo
      transfer. Immediately after weaning of the first litter, a second surgical embryo
      transfer was performed into the same oviduct. Virgin females of comparable age to
      the reused mothers served as controls and underwent the same procedure. The first
      surgery did not affect the success of the second embryo transfer. Histological
      sections showed excellent wound healing without relevant impairment of involved
      tissues. We observed no differences in pregnancy rates or litter sizes between
      the transfer groups. Most importantly, we found no change in behavior indicating
      reduced well-being and no increase of corticosterone metabolites in the feces of
      surrogate mothers reused for a second embryo transfer. We conclude that a second
      embryo transfer in mice is feasible with regard to reproductive and animal
      welfare aspects.

PMID- 21880947
TI  - Tumor necrosis factor alpha may act as an intraovarian mediator of luteinizing
      hormone-induced oocyte maturation in trout.
AB  - In fish, like in other vertebrates, luteinizing hormone (Lh) is an essential
      hormone for the completion of oocyte maturation. In salmonid fish (i.e., salmon
      and trout), oocyte maturation is induced by Lh through its stimulation of the
      production of the maturation-inducing steroid, 17alpha,20beta-dihydroxy-4-pregnen
      3-one (17,20beta-P). In mammals, several factors, including ovarian cytokines and
      growth factors, have been reported to contribute to the regulation of oocyte
      maturation. In fish, growing evidence suggests that tumor necrosis factor alpha
      (hereafter referred to as Tnf) could play multiple physiological roles in the
      control of ovarian function. In the present study, we have investigated the
      possible involvement of Tnf in the regulation of oocyte maturation in brown trout
      (Salmo trutta). Our results show that in vitro treatment of brown trout
      preovulatory follicles with coho salmon (Oncorhynchus kisutch) Lh (sLh)
      significantly increased oocyte maturation, as assessed by germinal vesicle
      breakdown (GVBD), and that this effect was blocked by TAPI-1 (an inhibitor of Tnf
      converting enzyme or Tace/Adam17). Furthermore, treatment of preovulatory
      follicles with sLh increased the expression of tnf and tace/adam17 as well as the
      secretion of the Tnf protein. Importantly, recombinant trout Tnf (rtTnf)
      significantly increased GVBD in vitro. Our results also show that the stimulatory
      effects of rtTnf on oocyte maturation may be the result of the direct involvement
      of rtTnf in stimulating the production of the maturation-inducing steroid as
      evidenced, first, by the stimulatory effects of rtTnf on 17,20beta-P production
      in vitro and on the expression of cholesterol side-chain cleavage P450 cytochrome
      (p450scc) and 20beta-hydroxysteroid dehydrogenase/carbonyl reductase 1 (cbr1),
      the enzyme responsible for the production of 17,20beta-P, and, second, by the
      ability of TAPI-1 to block the stimulatory effects of sLh on 17,20beta-P
      production and cbr1 expression. Furthermore, sLh and rtTnf increased the
      expression of the Lh receptor (lhr) and decreased the expression of aromatase
      (cyp19a1), and TAPI-1 completely blocked the effects of sLh. These results
      strongly suggest that Tnf may contribute to the regulation of oocyte maturation
      by Lh in trout.

PMID- 21880949
TI  - Shoulder sport-specific impairments after arthroscopic Bankart repair: a
      prospective longitudinal assessment.
AB  - BACKGROUND: Reports of return to shoulder-dependent sport after surgical
      stabilization previously underestimated impairments, which were not reflected in
      the score systems used. HYPOTHESIS: Return to shoulder-dependent sport depends on
      the type of sport performed. STUDY DESIGN: Case series; Level of evidence, 4.
      METHODS: Forty-seven athletes (26.9 years of age at surgery) who underwent
      isolated arthroscopic Bankart repair were longitudinally monitored by shoulder
      dependent sport-specific activity (Shoulder Sport Activity Score [SSAS]) and
      ability (Athletic Shoulder Outcome Scoring System [ASOSS]) scores and visual
      analog scales for reachieved proficiency level, sport-specific shoulder pain, and
      functional deficits. Data were assessed at 4 points of treatment: preoperatively,
      and postoperatively after 6, 16, and 32 months (P0-P3). Athletes were analyzed
      separately according to shoulder sport: noncollision/nonoverhead (G1), collision
      (G2), overhead (G3), and martial arts (G4). RESULTS: The G1 and G2 athletes had
      re-achieved the preinjury sport activity and sport proficiency status and
      excellent ASOSS scores after 32 months (SSAS(G1) = 7.2, SSAS(G2) = 8.1, ASOSS(G1)
      = 94.4, ASOSS(G2) = 95.2), whereas G3 and G4 athletes remained at an inferior
      activity level (SSAS(G3) = 8.0, SSAS(G4) = 8.3) and proficiency level. The ASOSS
      documented a prolonged period of shoulder rehabilitation for G3 and G4 athletes
      to reach a good shoulder-dependent sport ability outcome after 32 months
      (ASOSS(G3) = 89.0, ASOSS(G4) = 93.1). All groups recorded persisting limitations
      in visual analog scales for sport-specific shoulder function and pain. The
      established scores (Rowe = 95.9, Walch-Duplay = 93.3, Constant = 94.0) did not
      reflect these sport-specific impairments. Athletes with 5 or more preoperative
      dislocations had significantly longer surgery-to-sport resumption intervals with
      a prolonged proficiency recovery. CONCLUSION: The athletes' shoulder
      stabilization resulted in a prolonged rehabilitation depending on the functional
      demand of the performed shoulder-dependent sport, as shown by the specific
      shoulder sport score systems.

PMID- 21880948
TI  - Mediators of the Jak/STAT signaling pathway in human spermatozoa.
AB  - In their journey to acquire the ability to fertilize the egg, numerous
      intracellular signaling systems are activated in spermatozoa, leading to an
      increase in protein tyrosine phosphorylation. Although the JAK/STAT signaling
      pathway is usually associated with the activation of transcription of specific
      genes, our laboratory previously demonstrated the presence of the IL6 receptor
      (IL6R) and the Janus kinase 1 (JAK1) in human spermatozoa, a cell that is mostly
      transcriptionally inactive. In order to determine the importance of the JAK/STAT
      signaling pathway, our objectives were to identify and characterize the mediators
      of this system in human sperm. Cell fractionation and surface biotinylation
      assays clearly demonstrated that IL6R is expressed at the sperm membrane surface.
      The kinase JAK1 is enriched in membrane fractions and is activated during human
      sperm capacitation as suggested by its increase in phosphotyrosine content. Many
      signal transducer and activator of transcription (STAT) proteins are expressed in
      human sperm, including STAT1, STAT3, STAT4, STAT5, and STAT6. Among them, only
      STAT1 and STAT5 were detected in the cytosolic fraction. All the detected STAT
      proteins were enriched in the cytoskeletal structures. STAT4 was present in the
      perinuclear theca, whereas JAK1, STAT1, and STAT5 were detected in the fibrous
      sheath. Indirect immunofluorescence studies showed that JAK1 and STAT1
      colocalized in the neck region and that STAT4 is present at the equatorial
      segment and flagella. The presence of STAT proteins in sperm structural
      components suggests that their role is different from their well-known
      transcription factor activity in somatic cells, but further investigations are
      required to determine their role in sperm function.

PMID- 21880950
TI  - Management and outcomes of latissimus dorsi and teres major injuries in
      professional baseball pitchers.
AB  - BACKGROUND: Very little data exist on latissimus dorsi (LD) and teres major (TM)
      injuries in professional baseball pitchers. PURPOSE: This review was undertaken
      to report on the management and outcomes of baseball pitchers with injury to 1 or
      both of these muscles. STUDY DESIGN: Case series; Level of evidence, 4. METHODS:
      A retrospective review of 16 professional baseball pitchers diagnosed and treated
      for an LD and/or TM tear between 2002 and 2008 was performed. Magnetic resonance
      imaging confirmed the diagnosis in all cases. The mean age was 28.1 years. All
      were treated nonoperatively with rest, rehabilitation, and return to pitching
      after a throwing program. The injuries included tendon avulsions in 6 athletes
      and strains in 10. Length of disabled time, return to prior level of pitching,
      and recurrences were noted. RESULTS: Fifteen of 16 pitchers (94%) returned to the
      same or higher level of play. The mean time to throwing was 35.6 days. Mean time
      to pitching was 61.9 days. Nine of 16 injuries (56%) were season-ending. Mean
      total time lost for athletes returning the same season was 82.4 days. Two of 16
      pitchers (13%) sustained recurrent injuries. Prior shoulder and elbow injuries
      were noted in 75% (12 of 16). CONCLUSION: Injury of the LD and/or TM can occur in
      pitchers. Nonoperative treatment is successful in allowing a return to high-level
      pitching.

PMID- 21880951
TI  - Food acculturation drives dietary differences among Mexicans, Mexican Americans,
      and Non-Hispanic Whites.
AB  - Our aim was to examine the effects of food acculturation on Mexican Americans'
      (MA) diets, taking the Mexican diet as reference. We used nationally
      representative samples of children (2-11 y) and female adolescents and adults (12
      49 y) from the Mexican National Nutrition Survey 1999 and NHANES 1999-2006 to
      compare the diets of Mexicans (n = 5678), MA born in Mexico (MAMX) (n = 1488), MA
      born in the United States (MAUS) (n = 3654), and non-Hispanic white Americans (NH
      White) (n = 5473). One 24-h diet recall was used to examine the percentage
      consuming and percentage energy consumed from selected food groups. Most of the
      food groups analyzed displayed a fairly linear increase or decrease in percent
      energy/capita intake in this order: Mexican, MAMX, MAUS, NH-White. However, few
      significant differences were observed among the US subpopulations, especially
      among MAUS and NH-Whites. Overall, compared to Mexicans, the US subpopulations
      had greater intakes of saturated fat, sugar, dessert and salty snacks, pizza and
      French fries, low-fat meat and fish, high-fiber bread, and low-fat milk, as well
      as decreased intakes of corn tortillas, low-fiber bread, high-fat milk, and
      Mexican fast food. Furthermore, the patterns were similar in all age groups.
      Although we found a mix of positive and negative aspects of food acculturation,
      the overall proportion of energy obtained from unhealthy foods was higher among
      the US subpopulations. Our findings indicate that within one generation in the
      US, the influence of the Mexican diet is almost lost. In addition, our results
      reinforce the need to discourage critical unhealthful components of the American
      diet among MA.

PMID- 21880952
TI  - Probiotic Lactobacillus reuteri alleviates the response to gastric distension in
      rats.
AB  - Probiotic lactic acid bacteria have been reported to alleviate symptoms in
      patients with irritable bowel syndrome. However, they have not been tested for
      use in functional gastric disease. We therefore investigated if strains
      previously shown to protect from response to colorectal distension (CRD) in rats
      also modulate response to gastric distension (GD). Healthy, male Sprague-Dawley
      rats were treated with viable, heat-killed, gamma-irradiated Lactobacillus
      reuteri or viable Lactobacillus plantarum wild type (WT), L. plantarum Dlt
      mutant, conditioned medium or medium control (9 d), and subjected to GD under
      anesthesia using an i.g. Teflon catheter. Effects were measured by heart rate
      (HR) changes during noxious distension (60 mm Hg) compared to baseline HR values.
      We also investigated the localization of viable, green fluorescent protein
      transfected bacteria in the stomach mucosa. Viable L. reuteri decreased the
      bradycardia induced by noxious GD compared to placebo controls (P < 0.001). Heat
      killed or gamma-irradiated L. reuteri and conditioned medium did not have a
      protective effect in GD. Viable L. plantarum WT and Dlt-mutant, previously shown
      to be effective antinociceptive agents in CRD, showed no protective effect in GD.
      All viable bacteria were associated with the pars glandularis of the rat stomach.
      Thus, we conclude that the antinociceptive mechanisms of action of probiotic
      bacteria differ between the stomach and the colon. Symptom alleviation cannot be
      attributed to the localization of the bacteria in the stomach. Information
      derived from effects of CRD cannot be extrapolated to effects in the stomach,
      which are likely to be strain and organ specific.

PMID- 21880953
TI  - Creatine supplementation prevents the accumulation of fat in the livers of rats
      fed a high-fat diet.
AB  - The aim of the present study was to examine the effects of creatine
      supplementation on liver fat accumulation induced by a high-fat diet in rats.
      Rats were fed 1 of 3 different diets for 3 wk: a control liquid diet (C), a high
      fat liquid diet (HF), or a high-fat liquid diet supplemented with creatine (HFC).
      The C and HF diets contained, respectively, 35 and 71% of energy derived from
      fat. Creatine supplementation involved the addition of 1% (wt:v) of creatine
      monohydrate to the liquid diet. The HF diet increased total liver fat
      concentration, liver TG, and liver TBARS and decreased the hepatic S
      adenosylmethionine (SAM) concentration. Creatine supplementation normalized all
      of these perturbations. Creatine supplementation significantly decreased the
      renal activity of l-arginine:glycine amidinotransferase and plasma
      guanidinoacetate and prevented the decrease in hepatic SAM concentration in rats
      fed the HF diet. However, there was no change in either the
      phosphatidylcholine:phosphatidylethanolamine (PE) ratio or PE N-methyltransferase
      activity. The HF diet decreased mRNA for PPARalpha as well as 2 of its targets,
      carnitine palmitoyltransferase and long-chain acylCoA dehydrogenase. Creatine
      supplementation normalized these mRNA levels. In conclusion, creatine
      supplementation prevented the fatty liver induced by feeding rats a HF diet,
      probably by normalization of the expression of key genes of beta-oxidation.

PMID- 21880955
TI  - Differential effects of the trans-18:1 isomer profile of partially hydrogenated
      vegetable oils on cholesterol and lipoprotein metabolism in male F1B hamsters.
AB  - Trans-fatty acid consumption from partially hydrogenated vegetable oil (PHVO) has
      been positively associated with multiple cardiovascular disease risk factors and
      events. This study was designed to examine the effects of trans-fatty acid isomer
      profile of PHVO on plasma lipids and lipoproteins and hepatic expression of key
      genes involved in cholesterol and fatty acid metabolism. Thirty-three male F(1)B
      strain Syrian Golden Hamsters were allocated to 1 of 3 hypercholesterolemic diets
      containing (5% by weight): 1) tristearin [control fat (CON)]; 2) partially
      hydrogenated high-oleic acid sunflower oil (PH-SUN); or 3) partially hydrogenated
      high-linoleic acid safflower oil (PH-SAF). PH-SUN contained more trans-4 to trans
      10 18:1 compared with PH-SAF, which contained more trans-11 to trans-16 18:1. The
      addition of both PHVO to the diet increased plasma total cholesterol
      concentrations relative to CON, but only PH-SUN increased the plasma ratio of non
      HDL:HDL cholesterol compared with CON. PH-SUN increased VLDL (total, large, and
      medium) and IDL particle concentrations while decreasing total, medium, and small
      HDL particle concentrations relative to CON. Both PHVO diets increased the
      hepatic cholesterol ester concentration, whereas the hepatic TG concentration was
      lower in PH-SUN compared with PH-SAF and CON. Levels of hepatic LDL receptor, HMG
      CoA reductase, and sterol response element binding protein 1 mRNA were
      specifically reduced in the PH-SUN group compared to the CON group. Expression of
      SREBP1c was upregulated in both PHVO groups compared to CON, whereas only the PH
      SAF group had higher levels of the lipogenic enzymes acetyl-CoA carboxylase,
      fatty acid synthase, and stearoyl-CoA desaturase-1 compared to CON. These results
      indicate that differences in the trans-fatty acid profile of PHVO can
      differentially affect lipid and lipoprotein metabolism.

PMID- 21880954
TI  - Whole blueberry powder modulates the growth and metastasis of MDA-MB-231 triple
      negative breast tumors in nude mice.
AB  - Previous studies in our laboratory demonstrated that blueberry (BB) extract
      exhibited antitumor activity against MDA-MB-231 triple negative breast cancer
      (TNBC) cells and decreased metastatic potential in vitro. The current study
      tested 2 doses of whole BB powder, 5 and 10% (wt:wt) in the diet, against MDA-MB
      231 tumor growth in female nude mice. In this study, tumor volume was 75% lower
      in mice fed the 5% BB diet and 60% lower in mice fed the 10% BB diet than in
      control mice (P <= 0.05). Tumor cell proliferation (Ki-67) was lower in the 5 and
      10% BB-fed mice and cell death (Caspase 3) was greater in the 10% BB-fed mice
      compared to control mice (P <= 0.05). Gene analysis of tumor tissues from the 5%
      BB-fed mice revealed significantly altered expression of genes important to
      inflammation, cancer, and metastasis, specifically, Wnt signaling, thrombospondin
      2, IL-13, and IFNgamma. To confirm effects on Wnt signaling, analysis of tumor
      tissues from 5% BB-fed mice revealed lower beta-catenin expression and glycogen
      synthase kinase-3beta phosphorylation with greater expression of the beta-catenin
      inhibitory protein adenomatous polyposis coli compared to controls. A second
      study tested the ability of the 5% BB diet to inhibit MDA-MB-231-luc-D3H2LN
      metastasis in vivo. In this study, 5% BB-fed mice developed 70% fewer liver
      metastases (P = 0.04) and 25% fewer lymph node metastases (P = 0.09) compared to
      control mice. This study demonstrates the oral antitumor and metastasis activity
      of whole BB powder against TNBC in mice.

PMID- 21880956
TI  - Neutrophil transmigration triggers repair of the lung epithelium via beta-catenin
      signaling.
AB  - Injury to the epithelium is integral to the pathogenesis of many inflammatory
      lung diseases, and epithelial repair is a critical determinant of clinical
      outcome. However, the signaling pathways regulating such repair are incompletely
      understood. We used in vitro and in vivo models to define these pathways. Human
      neutrophils were induced to transmigrate across monolayers of human lung
      epithelial cells in the physiological basolateral-to-apical direction. This
      allowed study of the neutrophil contribution not only to the initial epithelial
      injury, but also to its repair, as manifested by restoration of transepithelial
      resistance and reepithelialization of the denuded epithelium. Microarray analysis
      of epithelial gene expression revealed that neutrophil transmigration activated
      beta-catenin signaling, and this was verified by real-time PCR, nuclear
      translocation of beta-catenin, and TOPFlash reporter activity. Leukocyte
      elastase, likely via cleavage of E-cadherin, was required for activation of beta
      catenin signaling in response to neutrophil transmigration. Knockdown of beta
      catenin using shRNA delayed epithelial repair. In mice treated with intratracheal
      LPS or keratinocyte chemokine, neutrophil emigration resulted in activation of
      beta-catenin signaling in alveolar type II epithelial cells, as demonstrated by
      cyclin D1 expression and/or reporter activity in TOPGAL mice. Attenuation of beta
      catenin signaling by IQ-1 inhibited alveolar type II epithelial cell
      proliferation in response to neutrophil migration induced by intratracheal
      keratinocyte chemokine. We conclude that beta-catenin signaling is activated in
      lung epithelial cells during neutrophil transmigration, likely via elastase
      mediated cleavage of E-cadherin, and regulates epithelial repair. This pathway
      represents a potential therapeutic target to accelerate physiological recovery in
      inflammatory lung diseases.

PMID- 21880957
TI  - Bacterial outer membrane channel for divalent metal ion acquisition.
AB  - The prevailing model of bacterial membrane function predicts that the outer
      membrane is permeable to most small solutes because of pores with limited
      selectivity based primarily on size. Here, we identified mnoP in the Gram
      negative bacterium Bradyrhizobium japonicum as a gene coregulated with the inner
      membrane Mn(2+) transporter gene mntH. MnoP is an outer membrane protein
      expressed specifically under manganese limitation. MnoP acts as a channel to
      facilitate the tranlocation of Mn(2+), but not Co(2+) or Cu(2+), into
      reconstituted proteoliposomes. An mnoP mutant is defective in high-affinity
      Mn(2+) transport into cells and has a severe growth phenotype under manganese
      limitation. We suggest that the outer membrane is a barrier to divalent metal
      ions that requires a selective channel to meet the nutritional needs of the cell.

PMID- 21880958
TI  - Characterization of bacterial communities in venous insufficiency wounds by use
      of conventional culture and molecular diagnostic methods.
AB  - Microbial infections delay wound healing, but the effect of the composition of
      the wound microbiome on healing parameters is unknown. To better understand
      bacterial communities in chronic wounds, we analyzed debridement samples from
      lower-extremity venous insufficiency ulcers using the following: conventional
      anaerobic and aerobic bacterial cultures; the Ibis T5000 universal biosensor
      (Abbott Molecular); and 16S 454 FLX titanium series pyrosequencing (Roche). Wound
      debridement samples were obtained from 10 patients monitored clinically for at
      least 6 months, at which point 5 of the 10 sampled wounds had healed.
      Pyrosequencing data revealed significantly higher bacterial abundance and
      diversity in wounds that had not healed at 6 months. Additionally,
      Actinomycetales was increased in wounds that had not healed, and Pseudomonadaceae
      was increased in wounds that had healed by the 6-month follow-up. Baseline wound
      surface area, duration, or analysis by Ibis or conventional culture did not
      reveal significant differences between wounds that healed after 6 months and
      those that did not. Thus, pyrosequencing identified distinctive baseline
      characteristics of wounds that did not heal by the 6-month follow-up, furthering
      our understanding of potentially unique microbiome characteristics of chronic
      wounds.

PMID- 21880959
TI  - Beta-D-glucan detection as a diagnostic test for invasive aspergillosis in
      immunocompromised critically ill patients with symptoms of respiratory infection:
      an autopsy-based study.
AB  - Beta-(1,3)-D-glucan (BG) detection is an emerging tool to diagnose invasive
      fungal infections (IFIs). Invasive aspergillosis (IA) is the second most common
      IFI in immunocompromised intensive care unit (ICU) patients. We retrospectively
      analyzed the serum BG concentration (Fungitell; Associates of Cape Cod) in
      immunocompromised ICU patients with proven IA and in immunocompromised ICU
      patients in whom autopsy failed to show IFI. The study was performed in a 17-bed
      medical ICU in a 1,900-bed referral hospital. Patients at risk for IA were
      eligible for inclusion when at least two additional clinical signs were present.
      Patients with other IFIs were excluded. Fourteen patients with IA and 33 patients
      who had no IFI were eligible for inclusion. Serum BG levels were significantly
      higher in patients with IA than patients without an IFI (P < 0.01). Using a
      cutoff of 140 pg/ml, the sensitivity and specificity were 85.7 and 69.7%,
      respectively; the positive and negative predictive values were 54.5 and 92.0%,
      respectively. The positive and negative likelihood ratios were 2.83 and 0.21,
      respectively. Although serum BG concentrations were higher in immunocompromised
      ICU patients with IA than in patients with the same risk factors who did not have
      IFI on autopsy, the moderate performance characteristics of this test limit its
      use as a diagnostic test for IA in this population.

PMID- 21880960
TI  - Canada's first case of a multidrug-resistant Corynebacterium diphtheriae strain,
      isolated from a skin abscess.
AB  - A toxigenic Corynebacterium diphtheriae biovar mitis sequence type 136 (ST136)
      strain was recovered from a toe infection of an unvaccinated patient recently
      returned from India. The isolate was resistant to clindamycin, erythromycin (ermX
      positive), tetracycline, and trimethoprim-sulfamethoxazole, intermediate to
      ceftriaxone and cefotaxime, and had high MICs for telithromycin and
      chloramphenicol but was sensitive to other drugs.

PMID- 21880961
TI  - Perirectal swab surveillance for Clostridium difficile by use of selective broth
      preamplification and real-time PCR detection of tcdB.
AB  - Active surveillance testing to identify and isolate asymptomatic carriers of
      toxigenic Clostridium difficile has been limited by the lack of a test that is
      sensitive, specific, and timely enough to serve as an infection control tool. We
      tested DNA preamplified from perirectal surveillance specimens in a liquid medium
      selective for C. difficile by using a modified commercial real-time PCR assay.
      All fermenting specimens were subcultured, and isolates were tested for
      toxigenicity. Culture-positive toxigenic isolates served as the gold standard for
      comparison with the broth preamplification/PCR assay. The limit of detection for
      the assay was 1 CFU. Relative to toxigenic anaerobic culture, the sensitivity,
      specificity, and positive and negative predictive values of this assay were 70/70
      (100.0%), 422/426 (99.1%), 70/74 (94.6%), and 422/422 (100.0%), respectively.
      These data demonstrate that selective broth preamplification and real-time PCR of
      perirectal swab specimens constitute a practical approach to the detection of
      asymptomatic C. difficile carriage.

PMID- 21880962
TI  - Accuracy of carbapenem nonsusceptibility for identification of KPC-possessing
      Enterobacteriaceae by use of the revised CLSI breakpoints.
AB  - Using the updated 2010 CLSI carbapenem breakpoints for the Enterobacteriaceae,
      nonsusceptibility to ertapenem and imipenem predicted the presence of bla(KPC)
      poorly, especially among Escherichia coli and Enterobacter species. In regions
      where KPC-producing bacteria are endemic, testing for nonsusceptibility to
      meropenem may provide improved accuracy in identifying these isolates.

PMID- 21880963
TI  - Rapid identification and validation of specific molecular targets for detection
      of Escherichia coli O104:H4 outbreak strain by use of high-throughput sequencing
      data from nine genomes.

PMID- 21880964
TI  - Multilocus sequence typing of Streptococcus pneumoniae by use of mass
      spectrometry.
AB  - Multilocus sequence typing (MLST) is an important tool for the global
      surveillance of bacterial pathogens that is performed by comparing the sequences
      of designated housekeeping genes. We developed and tested a novel mass
      spectrometry-based method for MLST of Streptococcus pneumoniae. PCR amplicons
      were subjected to in vitro transcription and base-specific cleavage, followed by
      analysis of the resultant fragments by using matrix-assisted laser desorption
      ionization-time of flight mass spectrometry (MALDI-TOF MS). Comparison of the
      cleavage fragment peak patterns to a reference sequence set permitted automated
      identification of alleles. Validation experiments using 29 isolates of S.
      pneumoniae revealed that the results of MALDI-TOF MS MLST matched those obtained
      by traditional sequence-based MLST for 99% of alleles and that the MALDI-TOF MS
      method accurately identified two single-nucleotide variations. The MADLI-TOF MS
      method was then used for MLST analysis of 43 S. pneumoniae isolates from Papua
      New Guinean children. The majority of the isolates present in this population
      were not clonal and contained seven new alleles and 30 previously unreported
      sequence types.

PMID- 21880965
TI  - Xpert MTB/RIF for rapid diagnosis of tuberculous lymphadenitis from fine-needle
      aspiration biopsy specimens.
AB  - This study demonstrates the excellent diagnostic accuracy of the Xpert MTB/RIF
      test in patients with tuberculous lymphadenitis. The test sensitivity and
      specificity were 96.7% (95% confidence interval [CI], 86.6 to 100%) and 88.9%
      (95% CI, 69.6 to 100%), respectively, and it correctly identified 6/6 (100%) of
      the cytology smear-negative/culture-positive cases and 1 of 2 (50%) rifampin
      resistant cases.

PMID- 21880967
TI  - Comparison of performance of the novel chromogenic spectra VRE agar to that of
      bile esculin azide and Campylobacter agars for detection of vancomycin-resistant
      enterococci in fecal samples.
AB  - A total of 142 stool specimens were evaluated for vancomycin-resistant
      enterococcus (VRE). Twenty-four-hour sensitivities and specificities,
      respectively, were 98% and 95% for Spectra VRE chromogenic agar (Remel, Lenexa,
      KS), 86% and 92% for bile esculin azide with vancomycin (BEAV; Remel), and 96.5%
      and 92% for Campylobacter agar (CAMPY; Remel). Spectra VRE and CAMPY are
      significantly more sensitive at 24 h than BEAV.

PMID- 21880966
TI  - Nineteen cases of Buruli ulcer diagnosed in Japan from 1980 to 2010.
AB  - The etiology, clinical manifestations, and treatment of 19 sporadic cases of
      Buruli ulcer (BU) in Japan are described. The cases originated in different
      regions of Honshu Island, with no evidence of patient contact with an aquatic
      environment. The majority (73.7%) of cases occurred in females, with an average
      age of 39.1 years for females and 56.8 years for males. All patients developed
      ulcers on exposed areas of the skin (e.g., face, extremities). Most ulcers were
      <5 cm in diameter (category I), except in one severe progressive case (category
      II). Pain was absent in 10 of the 19 cases. Fourteen ulcers were surgically
      excised, and nine patients needed skin grafting. All cases were treated with
      various antibiotic regimens, with no reported recurrences as of March 2011.
      Mycobacterium ulcerans-specific IS2404 was detected in all cases. Ten isolates
      had identical 16S rRNA gene sequences, which were similar to those of M.
      ulcerans. However, the rpoB gene showed a closer resemblance to Mycobacterium
      marinum or Mycobacterium pseudoshottsii. PCR identified pMUM001 in all isolates
      but failed to detect one marker. DNA-DNA hybridization misidentified all isolates
      as M. marinum. The drug susceptibility profile of the isolates also differed from
      that of M. ulcerans. Sequence analysis revealed "Mycobacterium ulcerans subsp.
      shinshuense" as the etiologic agent of BU in Japan. Clinical manifestations were
      comparable to those of M. ulcerans but differed as follows: (i) cases were not
      concentrated in a particular area; (ii) there was no suspected connection to an
      aquatic environment; (iii) drug susceptibility was different; and (iv)
      bacteriological features were different.

PMID- 21880968
TI  - Clinical validation of the cobas 4800 HPV test for cervical screening purposes.
AB  - This study shows that the clinical performance and reproducibility of the cobas
      4800 HPV test for high-risk human papillomavirus (HPV) detection fulfill the
      criteria as formulated in international guidelines of HPV test requirements for
      cervical screening purposes. Accordingly, the cobas 4800 HPV test can be
      considered clinically validated for cervical screening.

PMID- 21880969
TI  - Analysis of multilocus sequence typing for identification of Leptospira isolates
      in Brazil.
AB  - A collection of 101 Leptospira isolates was tested by multilocus sequence typing
      (MLST) and by traditional serotyping. MLST divided the isolates into 4 sequence
      types (STs), while serotyping classified them into 6 serogroups. Two isolates
      failed to generate products for some genes by MLST. MLST was less discriminatory
      than serotyping for uncommonly occurring isolates from humans in Brazil.

PMID- 21880970
TI  - Novel IS711 chromosomal location useful for identification of marine mammal
      Brucella genotype ST27, which is associated with zoonotic infection.
AB  - We report a novel IS711 chromosomal location that is specific for the Brucella
      genotype ST27 previously associated with Pacific marine mammals and human
      zoonotic infection in New Zealand and Peru. Our data support the previous
      observation that this peculiar genotype is distinct from those commonly isolated
      from the Atlantic and currently classified within the species B. ceti and B.
      pinnipedialis.

PMID- 21880971
TI  - Comparative utility of cytokine levels and quantitative RD-1-specific T cell
      responses for rapid immunodiagnosis of tuberculous meningitis.
AB  - The rapid diagnosis of tuberculous meningitis (TBM) is problematic. We found in
      150 patients with suspected TBM that, similar to RD-1-specific quantitative
      cerebrospinal fluid (CSF) T-cell responses, unstimulated CSF gamma interferon
      (IFN-gamma) levels when used together with other rapid confirmatory tests (Gram
      stain and cryptococcal latex agglutination test) may allow the accurate and rapid
      diagnosis of TBM in a setting in which tuberculosis (TB) and HIV are endemic. In
      resource-poor settings, a clinical prediction rule (CPR) may be useful to
      clinicians, and thus the IFN-gamma assay may potentially need to be used only
      when the clinical score is below a prespecified threshold. These preliminary
      findings will need to be confirmed in further studies.

PMID- 21880972
TI  - Prevalence and density-related concordance of three diagnostic tests for malaria
      in a region of Tanzania with hypoendemic malaria.
AB  - Accurate malaria diagnosis has dual roles in identification of symptomatic
      persons for effective malaria treatment and also enumeration of asymptomatic
      persons who contribute to the epidemiologic determinants of transmission. Three
      currently used diagnostic tests, microscopy, rapid diagnostic tests (RDTs), and
      real-time PCR, all have different sensitivities and specificities, which are
      parasite density dependent. Here, we compare their concordance among 451 febrile
      episodes in a cohort of 2,058 children and adults followed over 6 months in a
      region in central Tanzania with hypoendemic malaria. Microscopy, a histidine-rich
      protein-based RDT, and two different real-time PCR gene probes detected
      Plasmodium falciparum in 20, 54, 41, and 78 episodes of fever, respectively. They
      had complete concordance in only 9 episodes. Real-time PCR with an 18S probe was
      more sensitive than with a mitochondrial probe for cytochrome b despite higher
      copy numbers of mitochondrial DNA. Both PCR yields were increased 4-fold by
      glycogen/acetate precipitation with low-speed centrifugation. Duplicate PCR
      increases low-density malaria detection. RDT had the highest number of unique
      positives, presumably from persistent antigen despite the absence of parasites,
      although RDT did not detect 3 parasitemias with over 1,000 parasites/MUl. In a
      latent class analysis, real-time PCR had significantly higher sensitivity than
      did microscopy or RDT. Agreement between real-time PCR, RDT, and microscopy was
      highest in March and April, when both the P. falciparum parasite rate and
      parasite densities are highest. Real-time PCR is more sensitive and specific than
      RDT and microscopy in low-prevalence, low-parasite-density settings.

PMID- 21880973
TI  - First report of disseminated Mycobacterium skin infections in two liver
      transplant recipients and rapid diagnosis by hsp65 gene sequencing.
AB  - We present here the first report of disseminated skin Mycobacterium infections in
      two liver transplant recipients, in which hsp65 gene sequencing was used for
      rapid species identification. Both patients had hepatitis B virus-related
      cirrhosis and diabetes mellitus and presented with progressive generalized,
      nodular skin lesions. In one patient, a 50-year-old woman who had frequent
      contact with marine fish, an acid-fast bacillus was isolated from skin biopsy
      tissue after 2 months of culture. While awaiting phenotypic identification
      results, hsp65 gene sequencing showed that it was most closely related to that of
      Mycobacterium marinum with 100% nucleotide identity. The patient was treated with
      oral rifampin, ethambutol, and moxifloxacin. In the other patient, a 59-year-old
      woman, direct PCR for Mycobacterium using hsp65 gene from skin biopsy tissue was
      positive, with the sequence most closely related to that of M. haemophilum with
      100% nucleotide identity. Based on PCR results, the patient was treated with
      clarithromycin, ethambutol, moxifloxacin, and amikacin. A strain of M.
      haemophilum was only isolated after 3 months. Skin lesions of both patients
      resolved after 1 year of antimycobacterial therapy. Nontuberculous Mycobacterium
      infections should be considered in liver transplant recipients presenting with
      chronic, nodular skin lesions. This report highlights the crucial role of hsp65
      gene PCR and sequencing on both cultured isolates and direct clinical specimens
      for rapid diagnosis of slow-growing Mycobacterium infection.

PMID- 21880974
TI  - Development of a multiplex PCR assay targeting O-antigen modification genes for
      molecular serotyping of Shigella flexneri.
AB  - Shigella flexneri is the major Shigella species that causes diarrheal disease in
      developing countries. It is further subdivided into 15 serotypes based on O
      antigen structure. Serotyping of S. flexneri is important for epidemiological
      purposes. In this study, we developed a multiplex PCR assay targeting the O
      antigen synthesis gene wzx and the O-antigen modification genes gtrI, gtrIC,
      gtrII, oac, gtrIV, gtrV, and gtrX for molecular serotyping of S. flexneri. The
      multiplex PCR assay contained eight sets of specific PCRs in a single tube and
      can identify 14 of the 15 serotypes (the exception being serotype Xv) of S.
      flexneri recognized thus far. A nearly perfect concordance (97.8%) between
      multiplex PCR assay and slide agglutination was observed when 358 S. flexneri
      strains of various serotypes were analyzed, except that 8 strains were carrying
      additional cryptic and/or defective serotype-specific genes. The multiplex PCR
      assay provides a rapid and specific method for the serotype identification of S.
      flexneri.

PMID- 21880975
TI  - Characterization of Vibrio cholerae O1 El Tor biotype variant clinical isolates
      from Bangladesh and Haiti, including a molecular genetic analysis of virulence
      genes.
AB  - Vibrio cholerae serogroup O1, the causative agent of the diarrheal disease
      cholera, is divided into two biotypes: classical and El Tor. Both biotypes
      produce the major virulence factors toxin-coregulated pilus (TCP) and cholera
      toxin (CT). Although possessing genotypic and phenotypic differences, El Tor
      biotype strains displaying classical biotype traits have been reported and
      subsequently were dubbed El Tor variants. Of particular interest are reports of
      El Tor variants that produce various levels of CT, including levels typical of
      classical biotype strains. Here, we report the characterization of 10 clinical
      isolates from the International Centre for Diarrhoeal Disease Research,
      Bangladesh, and a representative strain from the 2010 Haiti cholera outbreak. We
      observed that all 11 strains produced increased CT (2- to 10-fold) compared to
      that of wild-type El Tor strains under in vitro inducing conditions, but they
      possessed various TcpA and ToxT expression profiles. Particularly, El Tor variant
      MQ1795, which produced the highest level of CT and very high levels of TcpA and
      ToxT, demonstrated hypervirulence compared to the virulence of El Tor wild-type
      strains in the infant mouse cholera model. Additional genotypic and phenotypic
      tests were conducted to characterize the variants, including an assessment of
      biotype-distinguishing characteristics. Notably, the sequencing of ctxB in some
      El Tor variants revealed two copies of classical ctxB, one per chromosome,
      contrary to previous reports that located ctxAB only on the large chromosome of
      El Tor biotype strains.

PMID- 21880976
TI  - Evaluation of Luminex xTAG fungal analyte-specific reagents for rapid
      identification of clinically relevant fungi.
AB  - Invasive fungal infections (IFI) remain a serious threat to immunocompromised
      hosts. Current diagnostic methods, including fungal culture and antigen
      detection, are slow and often lack specificity. Rapid diagnostic tools with
      increased sensitivity and specificity could improve the care of patients with
      IFI. Recently, Luminex Molecular Diagnostics (Toronto, Canada) developed 23
      analyte-specific reagents (ASRs) for the detection of the most common clinically
      relevant fungi. This study's objective was to evaluate the sensitivity and
      specificity of a subset of these ASRs for fungal isolates and clinical specimens.
      Previously characterized fungal and bacterial isolates (n = 110), blood culture
      specimens (n = 34), and respiratory specimens (n = 44) were tested using either a
      Candida 7-plex panel (Candida albicans, Candida glabrata, Candida tropicalis,
      Candida parapsilosis, Candida lusitaniae, Candida guilliermondii, and Candida
      krusei) or a mold 11-plex panel (Aspergillus fumigatus, Aspergillus flavus,
      Aspergillus niger, Aspergillus terreus, Scedosporium prolificans, Scedosporium
      apiospermum, Fusarium oxysporum/Fusarium solani, Rhizopus arrhizus, Rhizopus
      microsporus, Mucor indicus, and Cunninghamella bertholletiae). The Candida 7-plex
      panel correctly identified all Candida isolates as confirmed by fungal culture
      and biochemical tests, for a sensitivity and specificity of 100%. The mold 11
      plex panel correctly identified all mold isolates tested except for A. niger.
      Fungal isolates of Rhizopus and Mucor species were not detected, either, although
      they could represent species other than those targeted by the ASRs. Further
      evaluation will be necessary to confirm the sensitivities of some of the mold
      ASRs. Implementation of these ASRs will allow same-day detection of fungal DNA in
      clinical specimens.

PMID- 21880977
TI  - Antiretroviral therapy initiation in France: adherence to national guidelines and
      outcome.
AB  - OBJECTIVES AND METHODS: Retrospective study of all patients who started
      antiretroviral therapy (ART) in 2007 in a single center in Paris, with baseline
      characteristics and 1-year outcome, to assess adherence to national guidelines.
      RESULTS: We analyzed 118 patients. Time of ART initiation was in agreement with
      the guidelines for only 64 (54.2%) patients. Fifty patients (42%) started ART
      with AIDS or a CD4 count <200 cells/mm(3). In all, 62 (52%) and 47 patients (40%)
      received a combination of 2 nucleoside analogues with efavirenz (EFV) and 1
      ritonavir-boosted protease inhibitor (PI/r), respectively. Treatment regimens
      were in accordance with the guidelines for 114 patients (97%). At 1 year, 16
      patients (13.5%) were lost to follow-up, only 5 (4.9%) experienced HIV disease
      progression or death, but 19 (18.6%) required hospitalization. Antiretroviral
      therapy was changed in 21 patients (21%). Ten patients (8.4%) experienced
      virologic failure. CONCLUSION: Antiretroviral therapy was in agreement with
      guidelines for the choice of combination but was often initiated too late.

PMID- 21880979
TI  - Cutting edge: virus selectively primes human langerhans cells for CD70 expression
      promoting CD8+ T cell responses.
AB  - The two outermost compartments of skin are populated by different Ag-presenting
      dendritic cell types. Epidermal Langerhans cells (LCs) are evolutionarily adapted
      to the continuous presence of harmless skin commensals by the selective lack of
      cell surface TLRs that sense bacteria. In this article, we analyze the ability of
      LCs and dermal dendritic cells (DDCs) to respond to virus infection. Live virus
      and intracellular TLR3-agonist dsRNA commit LCs more effectively than DDCs to
      stimulate naive CD8(+) T cell expansion and their differentiation into effector
      cells. This potent CD8(+) T cell-promoting capacity of LCs is causally related to
      high levels of virus-induced CD70 expression but not to IL-12 production. These
      data suggest a remarkable specialization of LCs in the induction of pathogen
      class-specific adaptive immunity. Whereas LCs ignore bacteria, they are superior
      to DDCs to initiate effective CD70-mediated CD8(+) T cells in response to virus
      stimulation.

PMID- 21880978
TI  - The process of macrophage migration promotes matrix metalloproteinase-independent
      invasion by tumor cells.
AB  - Tumor-associated macrophages are known to amplify the malignant potential of
      tumors by secreting a variety of cytokines and proteases involved in tumor cell
      invasion and metastasis, but how these macrophages infiltrate tumors and whether
      the macrophage migration process facilitates tumor cell invasion remain poorly
      documented. To address these questions, we used cell spheroids of breast
      carcinoma SUM159PT cells as an in vitro model of solid tumors. We found that
      macrophages used both the mesenchymal mode requiring matrix metalloproteinases
      (MMPs) and the amoeboid migration mode to infiltrate tumor cell spheroids.
      Whereas individual SUM159PT cells invaded Matrigel using an MMP-dependent
      mesenchymal mode, when they were grown as spheroids, tumor cells were unable to
      invade the Matrigel surrounding spheroids. When spheroids were infiltrated or in
      contact with macrophages, tumor cell invasiveness was restored. It was dependent
      on the capacity of macrophages to remodel the matrix and migrate in an MMP
      independent mesenchymal mode. This effect of macrophages was much reduced when
      spheroids were infiltrated by Matrigel migration-defective Hck(-/-) macrophages.
      In the presence of macrophages, SUM159PT migrated into Matrigel in the proximity
      of macrophages and switched from an MMP-dependent mesenchymal migration to an
      amoeboid mode resistant to protease inhibitors.Thus, in addition to the well
      described paracrine loop between macrophages and tumor cells, macrophages can
      also contribute to the invasiveness of tumor cells by remodeling the
      extracellular matrix and by opening the way to exit the tumor and colonize the
      surrounding tissues in an MMP-dispensable manner.

PMID- 21880980
TI  - Heterogeneous and tissue-specific regulation of effector T cell responses by IFN
      gamma during Plasmodium berghei ANKA infection.
AB  - IFN-gamma and T cells are both required for the development of experimental
      cerebral malaria during Plasmodium berghei ANKA infection. Surprisingly, however,
      the role of IFN-gamma in shaping the effector CD4(+) and CD8(+) T cell response
      during this infection has not been examined in detail. To address this, we have
      compared the effector T cell responses in wild-type and IFN-gamma(-/-) mice
      during P. berghei ANKA infection. The expansion of splenic CD4(+) and CD8(+) T
      cells during P. berghei ANKA infection was unaffected by the absence of IFN
      gamma, but the contraction phase of the T cell response was significantly
      attenuated. Splenic T cell activation and effector function were essentially
      normal in IFN-gamma(-/-) mice; however, the migration to, and accumulation of,
      effector CD4(+) and CD8(+) T cells in the lung, liver, and brain was altered in
      IFN-gamma(-/-) mice. Interestingly, activation and accumulation of T cells in
      various nonlymphoid organs was differently affected by lack of IFN-gamma,
      suggesting that IFN-gamma influences T cell effector function to varying levels
      in different anatomical locations. Importantly, control of splenic T cell numbers
      during P. berghei ANKA infection depended on active IFN-gamma-dependent
      environmental signals--leading to T cell apoptosis--rather than upon intrinsic
      alterations in T cell programming. To our knowledge, this is the first study to
      fully investigate the role of IFN-gamma in modulating T cell function during P.
      berghei ANKA infection and reveals that IFN-gamma is required for efficient
      contraction of the pool of activated T cells.

PMID- 21880981
TI  - MicroRNA-155 is essential for the T cell-mediated control of Helicobacter pylori
      infection and for the induction of chronic Gastritis and Colitis.
AB  - MicroRNAs govern immune responses to infectious agents, allergens, and
      autoantigens and function by posttranscriptional repression of their target
      genes. In this paper, we have addressed the role of microRNA-155 (miR-155) in the
      control of Helicobacter pylori infection of the gastrointestinal tract and the
      development of H. pylori-induced chronic gastritis and associated gastric
      preneoplastic pathology. We show that miR-155 is upregulated in the gastric
      mucosa of experimentally infected mice and that miR-155(-/-) mice fail to control
      H. pylori infection as a result of impaired pathogen-specific Th1 and Th17
      responses. miR-155(-/-) mice are also less well protected against challenge
      infection after H. pylori-specific vaccination than their wild-type (wt)
      counterparts. As a consequence of their impaired T cell responses to H. pylori,
      miR-155(-/-) mice develop less severe infection-induced immunopathology
      manifesting as chronic atrophic gastritis, epithelial hyperplasia, and intestinal
      metaplasia. T cells from miR-155(-/-) mice that are activated by CD3/CD28 cross
      linking expand less and produce less IFN-gamma and IL-17 than wt T cells.
      Finally, we show in this paper using adoptive transfers that the phenotypes of
      miR-155(-/-) mice are likely due to T cell-intrinsic defects. In contrast to wt T
      cells, miR-155(-/-) T cells from infected donors do not control H. pylori
      infections in T cell-deficient recipients, do not differentiate into Th1 or Th17
      cells, and do not cause immunopathology. In addition, naive miR-155(-/-) T cells
      fail to induce chronic Th17-driven colitis in an adoptive transfer model. In
      conclusion, miR-155 expression is required for the Th17/Th1 differentiation that
      underlies immunity to H. pylori infection on the one hand and infection
      associated immunopathology on the other.

PMID- 21880982
TI  - Depletion of autoreactive plasma cells and treatment of lupus nephritis in mice
      using CEP-33779, a novel, orally active, selective inhibitor of JAK2.
AB  - Accumulating evidence suggests that autoreactive plasma cells play an important
      role in systemic lupus erythematosus (SLE). In addition, several proinflammatory
      cytokines promote autoreactive B cell maturation and autoantibody production.
      Hence, therapeutic targeting of such cytokine pathways using a selective JAK2
      inhibitor, CEP-33779 (JAK2 enzyme IC(50) = 1.3 nM; JAK3 enzyme IC(50)/JAK2 enzyme
      IC(50) = 65-fold), was tested in two mouse models of SLE. Age-matched, MRL/lpr or
      BWF1 mice with established SLE or lupus nephritis, respectively, were treated
      orally with CEP-33779 at 30 mg/kg (MRL/lpr), 55 mg/kg or 100 mg/kg (MRL/lpr and
      BWF1). Studies included reference standard, dexamethasone (1.5 mg/kg; MRL/lpr),
      and cyclophosphamide (50 mg/kg; MRL/lpr and BWF1). Treatment with CEP-33779
      extended survival and reduced splenomegaly/lymphomegaly. Several serum cytokines
      were significantly decreased upon treatment including IL-12, IL-17A, IFN-alpha,
      IL-1beta, and TNF-alpha. Anti-nuclear Abs and frequencies of autoantigen
      specific, Ab-secreting cells declined upon CEP-33779 treatment. Increased serum
      complement levels were associated with reduced renal JAK2 activity,
      histopathology, and spleen CD138(+) plasma cells. The selective JAK2 inhibitor
      CEP-33779 was able to mitigate several immune parameters associated with SLE
      advancement, including the protection and treatment of mice with lupus nephritis.
      These data support the possibility of using potent, orally active, small-molecule
      inhibitors of JAK2 to treat the debilitative disease SLE.

PMID- 21880984
TI  - Ocular surface APCs are necessary for autoreactive T cell-mediated experimental
      autoimmune lacrimal keratoconjunctivitis.
AB  - As specialized sentinels between the innate and adaptive immune response, APCs
      are essential for activation of Ag-specific lymphocytes, pathogen clearance, and
      generation of immunological memory. The process is tightly regulated; however,
      excessive or atypical stimuli may ignite activation of APCs in a way that allows
      self-Ag presentation to autoreactive T cells in the context of the necessary
      costimulatory signals, ultimately resulting in autoimmunity. Studies in both
      animal models and patients suggest that dry eye is a chronic CD4(+) T cell
      mediated ocular surface autoimmune-based inflammatory disease. Using a
      desiccating stress-induced mouse model of dry eye, we establish the fundamental
      role of APCs for both the generation and maintenance of ocular-specific
      autoreactive CD4(+) T cells. Subconjunctival administration of liposome
      encapsulated clodronate efficiently diminished resident ocular surface APCs,
      inhibited the generation of autoreactive CD4(+) T cells, and blocked their
      ability to cause disease. APC-dependent CD4(+) T cell activation required intact
      draining cervical lymph nodes, as cervical lymphadenectomy also inhibited CD4(+)
      T cell-mediated dry eye disease. In addition, local depletion of peripheral
      conjunctival APCs blocked the ability of dry eye-specific CD4(+) T cells to
      accumulate within the ocular surface tissues, suggesting that fully primed and
      targeted dry eye-specific CD4(+) T cells require secondary activation by resident
      ocular surface APCs for maintenance and effector function. These data demonstrate
      that APCs are necessary for the initiation and development of experimental dry
      eye and support the standing hypothesis that dry eye is a self-Ag-driven
      autoimmune disease.

PMID- 21880983
TI  - Epitope-specific human influenza antibody repertoires diversify by B cell
      intraclonal sequence divergence and interclonal convergence.
AB  - We generated from a single blood sample five independent human mAbs that
      recognized the Sa antigenic site on the head of influenza hemagglutinin and
      exhibited inhibitory activity against a broad panel of H1N1 strains. All five Abs
      used the V(H)3-7 and J(H)6 gene segments, but at least four independent clones
      were identified by junctional analysis. High-throughput sequence analysis of
      circulating B cells revealed that each of the independent clones were members of
      complex phylogenetic lineages that had diversified widely using a pattern of
      progressive diversification through somatic mutation. Unexpectedly, B cells
      encoding multiple diverging lineages of these clones, including many containing
      very few mutations in the Ab genes, persisted in the circulation. Conversely, we
      noted frequent instances of amino acid sequence convergence in the Ag combining
      sites exhibited by members of independent clones, suggesting a strong selection
      for optimal binding sites. We suggest that maintenance in circulation of a wide
      diversity of somatic variants of dominant clones may facilitate recognition of
      drift variant virus epitopes that occur in rapidly mutating virus Ags, such as
      influenza hemagglutinin. In fact, these Ab clones recognize an epitope that
      acquired three glycosylation sites mediating escape from previously isolated
      human Abs.

PMID- 21880985
TI  - Complement activation and complement receptors on follicular dendritic cells are
      critical for the function of a targeted adjuvant.
AB  - A detailed understanding of how activation of innate immunity can be exploited to
      generate more effective vaccines is critically required. However, little is known
      about how to target adjuvants to generate safer and better vaccines. In this
      study, we describe an adjuvant that, through complement activation and binding to
      follicular dendritic cells (FDC), dramatically enhances germinal center (GC)
      formation, which results in greatly augmented Ab responses. The nontoxic CTA1-DD
      adjuvant hosts the ADP-ribosylating CTA1 subunit from cholera toxin and a dimer
      of the D fragment from Staphylococcus aureus protein A. We found that T cell
      dependent, but not -independent, responses were augmented by CTA1-DD. GC
      reactions and serum Ab titers were both enhanced in a dose-dependent manner. This
      effect required complement activation, a property of the DD moiety. Deposition of
      CTA1-DD to the FDC network appeared to occur via the conduit system and was
      dependent on complement receptors on the FDC. Hence, Cr2(-/-) mice failed to
      augment GC reactions and exhibited dramatically reduced Ab responses, whereas
      Ribi adjuvant demonstrated unperturbed adjuvant function in these mice.
      Noteworthy, the adjuvant effect on priming of specific CD4 T cells was found to
      be intact in Cr2(-/-) mice, demonstrating that the CTA1-DD host both complement
      dependent and -independent adjuvant properties. This is the first demonstration,
      to our knowledge, of an adjuvant that directly activates complement, enabling
      binding of the adjuvant to the FDC, which subsequently strongly promoted the GC
      reaction, leading to augmented serum Ab titers and long-term memory development.

PMID- 21880986
TI  - CD134 plus CD137 dual costimulation induces Eomesodermin in CD4 T cells to
      program cytotoxic Th1 differentiation.
AB  - Cytotoxic CD4 Th1 cells are emerging as a therapeutically useful T cell lineage
      that can effectively target tumors, but until now the pathways that govern their
      differentiation have been poorly understood. We demonstrate that CD134 (OX40)
      costimulation programs naive self- and virus-reactive CD4 T cells to undergo in
      vivo differentiation into cytotoxic Th1 effectors. CD137 (4-1BB) costimulation
      maximized clonal expansion, and IL-2 was necessary for cytotoxic Th1
      differentiation. Importantly, the T-box transcription factor Eomesodermin was
      critical for inducing the cytotoxic marker granzyme B. CD134 plus CD137 dual
      costimulation also imprinted a cytotoxic phenotype on bystanding CD4 T cells.
      Thus, to our knowledge, the current study identifies for the first time a
      specific costimulatory pathway and an intracellular mechanism relying on
      Eomesodermin that induces both Ag-specific and bystander cytotoxic CD4 Th1 cells.
      This mechanism might be therapeutically useful because CD134 plus CD137 dual
      costimulation induced CD4 T cell-dependent tumoricidal function in a mouse
      melanoma model.

PMID- 21880987
TI  - Modulation of the murine CD8 gene complex following the targeted integration of
      human CD2-locus control region sequences.
AB  - The human CD2 (hCD2) locus control region (LCR) inserted in the mouse CD8 gene
      complex activates expression of the CD8 genes in T cell subsets in which the CD8
      locus is normally silenced (e.g., CD4(+) single-positive T cells). In this
      article, we show that, in conditional mCD8/hCD2-LCR (CD8/LCR) knock-in mice, the
      continuous presence of the hCD2-LCR is required for this effect. Deletion of the
      inserted hCD2-LCR in a developmental stage and cell lineage-specific manner
      revealed that the temporary presence of the LCR during early development does not
      permanently alter the expression pattern of the CD8 genes. As a result, cells
      that have been affected by the insertion of the LCR can convert to their destined
      phenotype once the LCR is removed. DNaseI hypersensitive sites 1 and 2 of the
      hCD2-LCR influence the expression of the CD8 genes in a similar manner as does
      the full LCR, whereas insertion of hypersensitive site 3 alone of the LCR does
      not result in a changed expression pattern. This analysis revealed a dynamic
      interaction between the hCD2-LCR and the endogenous regulatory elements of the
      CD8 genes.

PMID- 21880988
TI  - The conserved scavenger receptor cysteine-rich superfamily in therapy and
      diagnosis.
AB  - The scavenger receptor cysteine-rich (SRCR) superfamily of soluble or membrane
      bound protein receptors is characterized by the presence of one or several
      repeats of an ancient and highly conserved protein module, the SRCR domain. This
      superfamily (SRCR-SF) has been in constant and progressive expansion, now up to
      more than 30 members. The study of these members is attracting growing interest,
      which parallels that in innate immunity. No unifying function has been described
      to date for the SRCR domains, this being the result of the limited knowledge
      still available on the physiology of most members of the SRCR-SF, but also of the
      sequence versatility of the SRCR domains. Indeed, involvement of SRCR-SF members
      in quite different functions, such as pathogen recognition, modulation of the
      immune response, epithelial homeostasis, stem cell biology, and tumor
      development, have all been described. This has brought to us new information,
      unveiling the possibility that targeting or supplementing SRCR-SF proteins could
      result in diagnostic and/or therapeutic benefit for a number of physiologic and
      pathologic states. Recent research has provided structural and functional insight
      into these proteins, facilitating the development of means to modulate the
      activity of SRCR-SF members. Indeed, some of these approaches are already in use,
      paving the way for a more comprehensive use of SRCR-SF members in the clinic. The
      present review will illustrate some available evidence on the potential of well
      known and new members of the SRCR-SF in this regard.

PMID- 21880989
TI  - Mechanisms of penile erection and basis for pharmacological treatment of erectile
      dysfunction.
AB  - Erection is basically a spinal reflex that can be initiated by recruitment of
      penile afferents, both autonomic and somatic, and supraspinal influences from
      visual, olfactory, and imaginary stimuli. Several central transmitters are
      involved in the erectile control. Dopamine, acetylcholine, nitric oxide (NO), and
      peptides, such as oxytocin and adrenocorticotropin/alpha-melanocyte-stimulating
      hormone, have a facilitatory role, whereas serotonin may be either facilitatory
      or inhibitory, and enkephalins are inhibitory. The balance between contractant
      and relaxant factors controls the degree of contraction of the smooth muscle of
      the corpora cavernosa (CC) and determines the functional state of the penis.
      Noradrenaline contracts both CC and penile vessels via stimulation of alpha1
      adrenoceptors. Neurogenic NO is considered the most important factor for
      relaxation of penile vessels and CC. The role of other mediators, released from
      nerves or endothelium, has not been definitely established. Erectile dysfunction
      (ED), defined as the "inability to achieve or maintain an erection adequate for
      sexual satisfaction," may have multiple causes and can be classified as
      psychogenic, vasculogenic or organic, neurologic, and endocrinologic. Many
      patients with ED respond well to the pharmacological treatments that are
      currently available, but there are still groups of patients in whom the response
      is unsatisfactory. The drugs used are able to substitute, partially or
      completely, the malfunctioning endogenous mechanisms that control penile
      erection. Most drugs have a direct action on penile tissue facilitating penile
      smooth muscle relaxation, including oral phosphodiesterase inhibitors and
      intracavernosal injections of prostaglandin E1. Irrespective of the underlying
      cause, these drugs are effective in the majority of cases. Drugs with a central
      site of action have so far not been very successful. There is a need for
      therapeutic alternatives. This requires identification of new therapeutic targets
      and design of new approaches. Research in the field is expanding, and several
      promising new targets for future drugs have been identified.

PMID- 21880990
TI  - ISPD position statement on reducing the risks of peritoneal dialysis-related
      infections.

PMID- 21880991
TI  - Photosystem II supercomplex remodeling serves as an entry mechanism for state
      transitions in Arabidopsis.
AB  - Within dense plant populations, strong light quality gradients cause unbalanced
      excitation of the two photosystems resulting in reduced photosynthetic
      efficiency. Plants redirect such imbalances by structural rearrangements of the
      photosynthetic apparatus via state transitions and photosystem stoichiometry
      adjustments. However, less is known about the function of photosystem II (PSII)
      supercomplexes in this context. Here, we show in Arabidopsis thaliana that PSII
      supercomplex remodeling precedes and facilitates state transitions. Intriguingly,
      the remodeling occurs in the short term, paralleling state transitions, but is
      also present in a state transition-deficient mutant, indicating that PSII
      supercomplex generation is independently regulated and does not require light
      harvesting complex phosphorylation and movement. Instead, PSII supercomplex
      remodeling involves reversible phosphorylation of PSII core subunits
      (preferentially of CP43) and requires the luminal PSII subunit Psb27 for general
      formation and structural stabilization. Arabidopsis knockout mutants lacking
      Psb27 display highly accelerated state transitions, indicating that release of
      PSII supercomplexes is required for phosphorylation and subsequent movement of
      the antenna. Downregulation of PSII supercomplex number by physiological light
      treatments also results in acceleration of state transitions confirming the
      genetic analyses. Thus, supercomplex remodeling is a prerequisite and an
      important kinetic determinant of state transitions.

PMID- 21880992
TI  - Cognition after carotid endarterectomy or stenting: a randomized comparison.
AB  - OBJECTIVE: To compare the effect on cognition of carotid artery stenting (CAS)
      and carotid endarterectomy (CEA) for symptomatic carotid artery stenosis.
      METHODS: Patients randomized to CAS or CEA in the International Carotid Stenting
      Study (ICSS; ISRCTN25337470) at 2 participating centers underwent detailed
      neuropsychological examinations (NPE) before and 6 months after
      revascularization. Ischemic brain lesions were assessed with diffusion-weighted
      imaging before and within 3 days after revascularization. Cognitive test results
      were standardized into z scores, from which a cognitive sumscore was calculated.
      The primary outcome was the change in cognitive sumscore between baseline and
      follow-up. RESULTS: Of the 1,713 patients included in ICSS, 177 were enrolled in
      the 2 centers during the substudy period, of whom 140 had an NPE at baseline and
      120 at follow-up. One patient with an unreliable baseline NPE was excluded. CAS
      was associated with a larger decrease in cognition than CEA, but the between
      group difference was not statistically significant: -0.17 (95% CI -0.38 to 0.03;
      p = 0.092). Eighty-nine patients had a pretreatment MRI and 64 within 3 days
      after revascularization. New ischemic lesions were found twice as often after CAS
      than after CEA (relative risk 2.1; 95% CI 1.0 to 4.4; p = 0.041). CONCLUSIONS:
      Differences between CAS and CEA in effect on cognition were not statistically
      significant, despite a substantially higher rate of new ischemic lesions after
      CAS than after CEA. CLASSIFICATION OF EVIDENCE: This study provides Class III
      evidence that any difference between the effects of CAS and CEA on cognition at 6
      months after revascularization is small.

PMID- 21880993
TI  - Massive expansion of SCA2 with autonomic dysfunction, retinitis pigmentosa, and
      infantile spasms.
AB  - OBJECTIVE: To provide clinical data on a cohort of 6 patients with massive
      expansion (>200 CAG repeats) of spinocerebellar ataxia type 2 (SCA2) and
      investigate possible pathways of pathogenesis using bioinformatics analysis of
      ATXN2 networks. METHODS: We present data on 6 patients with massive expansion of
      SCA2 who presented in infancy with variable combinations of hypotonia, global
      developmental delay, infantile spasms, and retinitis pigmentosa. ATXN2 is known
      to interact with a network of synaptic proteins. To investigate pathways of
      pathogenesis, we performed bioinformatics analysis on ATXN2 combined with known
      genes associated with infantile spasms, retinitis pigmentosa, and synaptic
      function. RESULTS: All patients had a progressive encephalopathy with autonomic
      dysfunction, 4 had retinitis pigmentosa, and 3 had infantile spasms. The
      bioinformatics analysis led to several interesting findings. First, an
      interaction between ATXN2 and SYNJ1 may account for the development of retinitis
      pigmentosa. Second, dysfunction of postsynaptic vesicle endocytosis may be
      important in children with this progressive encephalopathy. Infantile spasms may
      be associated with interactions between ATXN2 and the postsynaptic structural
      proteins MAGI2 and SPTAN1. CONCLUSIONS: Severe phenotype in children with massive
      expansion of SCA2 may be due to a functional deficit in protein networks in the
      postsynapse, specifically involving vesicle endocytosis.

PMID- 21880995
TI  - Valproic acid as the AED of choice for patients with glioblastoma? The jury is
      out.

PMID- 21880994
TI  - Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial
      for glioblastoma.
AB  - OBJECTIVE: This analysis was performed to assess whether antiepileptic drugs
      (AEDs) modulate the effectiveness of temozolomide radiochemotherapy in patients
      with newly diagnosed glioblastoma. METHODS: The European Organization for
      Research and Treatment of Cancer (EORTC) 26981-22981/National Cancer Institute of
      Canada (NCIC) CE.3 clinical trial database of radiotherapy (RT) with or without
      temozolomide (TMZ) for newly diagnosed glioblastoma was examined to assess the
      impact of the interaction between AED use and chemoradiotherapy on survival. Data
      were adjusted for known prognostic factors. RESULTS: When treatment began, 175
      patients (30.5%) were AED-free, 277 (48.3%) were taking any enzyme-inducing AED
      (EIAED) and 135 (23.4%) were taking any non-EIAED. Patients receiving valproic
      acid (VPA) only had more grade 3/4 thrombopenia and leukopenia than patients
      without an AED or patients taking an EIAED only. The overall survival (OS) of
      patients who were receiving an AED at baseline vs not receiving any AED was
      similar. Patients receiving VPA alone (97 [16.9%]) appeared to derive more
      survival benefit from TMZ/RT (hazard ratio [HR] 0.39, 95% confidence interval
      [CI] 0.24-0.63) than patients receiving an EIAED only (252 [44%]) (HR 0.69, 95%
      CI 0.53-0.90) or patients not receiving any AED (HR 0.67, 95% CI 0.49-0.93).
      CONCLUSIONS: VPA may be preferred over an EIAED in patients with glioblastoma who
      require an AED during TMZ-based chemoradiotherapy. Future studies are needed to
      determine whether VPA increases TMZ bioavailability or acts as an inhibitor of
      histone deacetylases and thereby sensitizes for radiochemotherapy in vivo.

PMID- 21880996
TI  - Anatomy and physiology predict response to motor cortex stimulation after stroke.
AB  - OBJECTIVES: Preclinical studies found that epidural motor cortex stimulation
      improved motor deficits after stroke, but a phase III trial in humans did not
      corroborate these results. The current retrospective analysis examined subjects
      randomized to stimulation in order to identify features distinguishing responders
      from nonresponders. METHODS: Anatomic (MRI measures of gray matter thickness and
      of white matter tract injury) and physiologic methods (motor evoked responses)
      were examined as predictors of treatment response. RESULTS: Among 60 subjects
      randomized to cortical stimulation, both anatomic and physiologic measures at
      baseline predicted behavioral response to therapy. Anatomically, those achieving
      the primary efficacy endpoint had a smaller fraction of the corticospinal tract
      injured by stroke compared to those who did not (44% vs 72%, p < 0.04), and
      rarely had severe tract injury. Physiologically, the primary efficacy endpoint
      was reached more often (67%) by those with preserved motor evoked responses (MER)
      upon cortical stimulation compared to those lacking MER (27%, p < 0.05). Those
      with an elicitable MER also had a lower rate of precentral gyrus injury (0% vs
      33%, p < 0.05) by stroke, as compared to those lacking MER, and had higher gray
      matter volume compared to those lacking MER in regions including ipsilesional
      precentral gyrus. CONCLUSIONS: In this clinical stroke trial, the more that the
      physiologic integrity of the motor system was preserved, the more likely that a
      patient was to derive gains from subsequent therapy, consistent with preclinical
      models. Functional and structural preservation of key brain substrates are
      important to deriving gain from a restorative therapy.

PMID- 21880997
TI  - Novel p.Ile151Val mutation in VCP in a patient of African American descent with
      sporadic ALS.

PMID- 21880998
TI  - Imaging evolution of acute lacunar infarction: leukoariosis or lacune?
AB  - BACKGROUND: In acute lacunar infarction, MRI may overestimate eventual infarct
      size and the imaging evolution of acute lesions is not fully understood. Our
      objective was to examine eventual infarct size, the incidence of cavity
      formation, and factors associated with cavitation in patients presenting with
      acute lacunar infarction. METHODS: Patients with acute diffusion-weighted imaging
      (DWI) infarcts <=25 mm in diameter, in the distribution of a penetrating artery,
      who had a follow-up MRI or CT at least 1 month or longer from stroke onset were
      retrospectively included. We measured baseline lesion size on DWI and T2/fluid
      attenuated inversion recovery (FLAIR) and follow-up lesion size on T2/FLAIR and
      CT. Follow-up MRI and CT images were assessed for cavity formation. Predictors
      for cavitation were assessed in a multivariate model. RESULTS: We identified 75
      patients with lacunar infarction and follow-up CT or MRI, done 20.2 +/- 16.6 and
      21.2 +/- 17.4 months after stroke, respectively. Mean baseline DWI size was 13.5
      +/- 5.7 and T2/FLAIR size was 13.1 +/- 5.3 mm. Follow-up T2/FLAIR lesion size was
      8.2 +/- 3.4 mm and smaller than baseline DWI and T2/FLAIR (p = <0.001). Follow-up
      whole lesion size on CT scan was 7.1 +/- 4.1 and smaller than baseline DWI and
      T2/FLAIR (p = 0.001). Cavitation occurred in 23/38 (61%) MRI and 50/70 (70%) CT
      scans. We identified periventricular white matter lesions as a predictor of
      cavity formation by MRI and CT. CONCLUSION: Acute DWI significantly overestimates
      final infarct size. A third of lacunar infarcts do not develop a cavity.

PMID- 21880999
TI  - Bilateral somatosensory cortex disinhibition in complex regional pain syndrome
      type I.
AB  - OBJECTIVE: In a previous study, we found bilateral disinhibition in the motor
      cortex of patients with complex regional pain syndrome (CRPS). This finding
      suggests a complex dysfunction of central motor-sensory circuits. The aim of our
      present study was to assess possible bilateral excitability changes in the
      somatosensory system of patients with CRPS. METHODS: We measured paired-pulse
      suppression of somatosensory evoked potentials in 21 patients with unilateral
      CRPS I involving the hand. Eleven patients with upper limb pain of non
      neuropathic origin and 21 healthy subjects served as controls. Innocuous paired
      pulse stimulation of the median nerve was either performed at the affected and
      the unaffected hand, or at the dominant hand of healthy controls, respectively.
      RESULTS: We found a significant reduction of paired-pulse suppression in both
      sides of patients with CRPS, compared with control patients and healthy control
      subjects. CONCLUSION: These findings resemble our findings in the motor system
      and strongly support the hypothesis of a bilateral complex impairment of central
      motor-sensory circuits in CRPS I.

PMID- 21881000
TI  - A novel mechanism in maggot debridement therapy: protease in excretion/secretion
      promotes hepatocyte growth factor production.
AB  - Maggot debridement therapy (MDT) is effective for treating intractable wounds,
      but its precise molecular mechanism, including the association between MDT and
      growth factors, remains unknown. We administered MDT to nine patients (66.3 +/-
      11.8 yr, 5 male and 4 female) with intractable wounds of lower extremities
      because they did not respond to conventional therapies. Significant increases of
      hepatocyte growth factor (HGF) levels were observed in femoral vein blood during
      48 h of MDT (P < 0.05), but no significant change was found for vascular
      endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF),
      transforming growth factor-beta1 (TGF-beta1), or tumor necrosis factor-alpha (TNF
      alpha). We conducted NIH-3T3 cell stimulation assay to evaluate the relation
      between HGF and protease activity in excretion/secretion (ES) derived from
      maggots. Compared with the control group, HGF was significantly higher in the
      0.05 MUg/ml ES group (P < 0.01). Furthermore, protease inhibitors suppressed the
      increase of HGF (P < 0.05). The HGF expression was increased in proportion to the
      ES protein concentration of 0.025 to 0.5 MUg/ml. In fact, ES showed stronger
      capability of promoting HGF production and less cytotoxicity than chymotrypsin or
      bromelain. HGF is an important factor involved in cutaneous wound healing.
      Therefore, these results suggest that formation of healthy granulation tissue
      observed during MDT results from the increased HGF. Further investigation to
      identify molecules enhancing HGF expression by MDT will contribute greatly to
      drug target discovery for intractable wound healing therapy.

PMID- 21881002
TI  - Lithium reduces aquaporin-2 transcription independent of prostaglandins.
AB  - Vasopressin (AVP)-stimulated translocation and transcription of aquaporin-2
      (AQP2) water channels in renal principal cells is essential for urine
      concentration. Twenty percent of patients treated with lithium develop
      nephrogenic diabetes insipidus (NDI), a disorder in which the kidney is unable to
      concentrate urine. In vivo and in mouse collecting duct (mpkCCD) cells, lithium
      treatment coincides with decreased AQP2 abundance and inactivation of glycogen
      synthase kinase (Gsk) 3beta. This is paralleled in vivo by an increased renal
      cyclooxygenase 2 (COX-2) expression and urinary prostaglandin PGE(2) excretion.
      PGE(2) reduces AVP-stimulated water reabsorption, but its precise role in lithium
      induced downregulation of AQP2 is unclear. Using mpkCCD cells, we here
      investigated whether prostaglandins contribute to lithium-induced downregulation
      of AQP2. In these cells, lithium application reduced AQP2 abundance, which
      coincided with Gsk3beta inactivation and increased COX-2 expression. Inhibition
      of COX by indomethacin, leading to reduced PGE(2) and PGF(2alpha) levels, or
      dexamethasone-induced downregulation of COX-2 both increased AQP2 abundance,
      while PGE(2) addition reduced AQP2 abundance. However, lithium did not change the
      prostaglandin levels, and indomethacin and dexamethasone did not prevent lithium
      induced AQP2 downregulation. Further analysis revealed that lithium decreased
      AQP2 protein abundance, mRNA levels and transcription, while PGE(2) reduced AQP2
      abundance by increasing its lysosomal degradation, but not by reducing AQP2 gene
      transcription. In conclusion, our data reveal that in mpkCCD cells,
      prostaglandins decrease AQP2 protein stability by increasing its lysosomal
      degradation, indicating that in vivo paracrine-produced prostaglandins might have
      a role in lithium-induced NDI via this mechanism. However, lithium affects also
      AQP2 gene transcription, which is prostaglandin independent.

PMID- 21881001
TI  - TM4SF10 and ADAP interaction in podocytes: role in Fyn activity and nephrin
      phosphorylation.
AB  - TM4SF10 [transmembrane tetra(4)-span family 10] is a claudin-like cell junction
      protein that is transiently expressed during podocyte development where its
      expression is downregulated in differentiating podocytes coincident with the
      appearance of nephrin at the slit diaphragm. In a yeast two-hybrid screen, we
      identified adhesion and degranulation-promoting adaptor protein (ADAP), a well
      known Fyn substrate and Fyn binding partner, as a TM4SF10 interacting protein in
      mouse kidney. Using coimmunoprecipitation and immunohistochemistry experiments in
      cultured human podocytes, we show that TM4SF10 colocalizes with Fyn and ADAP but
      does not form a stable complex with Fyn. Cytoskeletal changes and phosphorylation
      events mediated by Fyn activity were reversed by TM4SF10 overexpression,
      including a decrease in the activating tyrosine phosphorylation of Fyn (Y(421)),
      suggesting TM4SF10 may have a regulatory role in suppressing Fyn activity. In
      addition, TM4SF10 was reexpressed following podocyte injury by puromycin
      aminonucleoside treatment, and its expression enhanced the abundance of high
      molecular-weight forms of nephrin indicating it may participate in a mechanism
      controlling nephrin's appearance at the plasma membrane. Therefore, these studies
      have identified ADAP as another Fyn adapter protein expressed in podocytes, and
      that TM4SF10, possibly through ADAP, may regulate Fyn activity. Since TM4SF10
      expression is temporally regulated during kidney development, these studies may
      help define a mechanism by which the slit diaphragm matures as a highly
      specialized cell junction during podocyte differentiation.

PMID- 21881003
TI  - Electrical slow waves in the mouse oviduct are dependent on extracellular and
      intracellular calcium sources.
AB  - Spontaneous contractions of the myosalpinx are critical for oocyte transport
      along the oviduct. Slow waves, the electrical events that underlie myosalpinx
      contractions, are generated by a specialized network of pacemaker cells called
      oviduct interstitial cells of Cajal (ICC-OVI). The ionic basis of oviduct
      pacemaker activity is unknown. Intracellular recordings and Ca(2+) imaging were
      performed to examine the role of extracellular and intracellular Ca(2+) sources
      in slow wave generation. RT-PCR was performed to determine the transcriptional
      expression of Ca(2+) channels. Molecular studies revealed most isoforms of L- and
      T-type calcium channels (Cav1.2,1.3,1.4,3.1,3.2,3.3) were expressed in
      myosalpinx. Reduction of extracellular Ca(2+) concentration ([Ca(2+)](o))
      resulted in the abolition of slow waves and myosalpinx contractions without
      significantly affecting resting membrane potential (RMP). Spontaneous Ca(2+)
      waves spread through ICC-OVI cells at a similar frequency to slow waves and were
      inhibited by reduced [Ca(2+)](o). Nifedipine depolarized RMP and inhibited slow
      waves; however, pacemaker activity returned when the membrane was repolarized
      with reduced extracellular K(+) concentration ([K(+)](o)). Ni(2+) also
      depolarized RMP but failed to block slow waves. The importance of ryanodine and
      inositol 1,4,5 trisphosphate-sensitive stores were examined using ryanodine,
      tetracaine, caffeine, and 2-aminoethyl diphenylborinate. Results suggest that
      although both stores are involved in regulation of slow wave frequency, neither
      are exclusively essential. The sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA)
      pump inhibitor cyclopiazonic acid inhibited pacemaker activity and Ca(2+) waves
      suggesting that a functional SERCA pump is necessary for pacemaker activity. In
      conclusion, results from this study suggest that slow wave generation in the
      oviduct is voltage dependent, occurs in a membrane potential window, and is
      dependent on extracellular calcium and functional SERCA pumps.

PMID- 21881004
TI  - Na+/H+ exchanger isoform 6 (NHE6/SLC9A6) is involved in clathrin-dependent
      endocytosis of transferrin.
AB  - In mammalian cells, nine conserved isoforms of the Na(+)/H(+) exchanger (NHE) are
      known to be important for pH regulation of the cytoplasm and organellar lumens.
      NHE1-5 are localized to the plasma membrane, whereas NHE6-9 are localized to
      distinct organelles. NHE6 is localized predominantly in endosomal compartments
      but is also found in the plasma membrane. To investigate the role of NHE6 in
      endocytosis, we established NHE6-knockdown HeLa cells and analyzed the effect of
      this knockdown on endocytotic events. The expression level of NHE6 in knockdown
      cells was decreased to ~15% of the level seen in control cells. Uptake of
      transferrin was also decreased. No effect was found on the endocytosis of
      epidermal growth factor or on the cholera toxin B subunit. Moreover, in the NHE6
      knockdown cells, transferrin uptake was found to be affected in the early stages
      of endocytosis. Microscopic analysis revealed that, at 2 min after the onset of
      endocytosis, colocalization of NHE6, clathrin, and transferrin was observed,
      which suggests that NHE6 was localized to endocytotic, clathrin-coated vesicles.
      In addition, in knockdown cells, transferrin-positive endosomes were acidified,
      but no effect was found on cytoplasmic pH. In cells overexpressing wild-type
      NHE6, increased transferrin uptake was observed, but no such increase was seen in
      cells overexpressing mutant NHE6 deficient in ion transport. The luminal pH in
      transferrin-positive endosomes was alkalized in cells overexpressing wild-type
      NHE6 but normal in cells overexpressing mutant NHE6. These observations suggest
      that NHE6 regulates clathrin-dependent endocytosis of transferrin via pH
      regulation.

PMID- 21881007
TI  - Congenital myotubular myopathy with a novel MTM1 gene mutation in a premature
      infant presenting with ventilator dependency and intrahepatic cholestasis.
AB  - Myotubular myopathy is a rare congenital disease characterized by hypotonia and
      respiratory compromise at birth in affected males. It causes high neonatal
      mortality. Most surviving newborns need prolonged ventilation and have
      significantly delayed motor development. Although all patients with congenital
      myotubular myopathy have respiratory problems such as atelectasis and recurrent
      lung infections, concurrent neonatal intrahepatic cholestasis is rare. We report
      a newborn with a myotubular myopathy, ventilator dependency, recurrent lung
      infections and pleural effusion, facial diplegia, ophthalmoplegia, and
      progressive intrahepatic cholestasis. A genetic study showed a novel mutation of
      the MTM1gene: c.1142 G>A (R381Q). We suggest that physicians consider probable
      concurrent disorders of other organs in neonates with congenital myotubular
      myopathy.

PMID- 21881006
TI  - Interictal encephalography can influence patient selection for methylprednisolone
      therapy in pediatric refractory epilepsy.
AB  - We describe our experience with intravenous methylprednisolone pulse therapy in
      older children with refractory epilepsy. Patients with refractory epilepsy, who
      were treated with steroids between 2005 and 2010, were retrospectively selected
      from the database of the pediatric epilepsy clinic at Assaf Harofeh Medical
      Center. Eight patients (5 boys) aged 1.1 to 9 years (5.2 +/- 2.6) were
      identified. Intravenous methylprednisolone 30 mg/kg/d was given to all patients
      for 5 days in addition to a stable dosage of the regular antiepileptic drugs.
      Transient side effects were reported in 4 of the patients during pulse therapy.
      Significant clinical improvement was noted in 4 patients, accompanied by a
      significant reduction of the amplitude of the spike-slow wave discharges on the
      electroencephalogram (EEG). Children with refractory epilepsy, abnormal EEG
      background, and high-amplitude spike-slow wave discharges appear to be the best
      candidates for intravenous methylprednisolone pulse therapy.

PMID- 21881005
TI  - Basolateral LPS inhibits NHE3 and HCOFormula absorption through TLR4/MyD88
      dependent ERK activation in medullary thick ascending limb.
AB  - Sepsis is associated with defects in renal tubule function, but the underlying
      mechanisms are incompletely understood. Recently, we demonstrated that Gram
      negative bacterial lipopolysaccharide (LPS) inhibits HCO(3)(-) absorption in the
      medullary thick ascending limb (MTAL) through activation of Toll-like receptor 4
      (TLR4). Here, we examined the mechanisms responsible for inhibition of HCO(3)(-)
      absorption by basolateral LPS. Adding LPS to the bath decreased HCO(3)(-)
      absorption by 30% in rat and mouse MTALs perfused in vitro. The inhibition of
      HCO(3)(-) absorption was eliminated by the mitogen-activated protein
      kinase/extracellular signal-regulated kinase (MEK)/ERK inhibitors U0126 and
      PD98059. LPS induced a rapid (<15 min) and sustained (up to 60 min) increase in
      ERK phosphorylation in microdissected MTALs that was blocked by PD98059. The
      effects of basolateral LPS to activate ERK and inhibit HCO(3)(-) absorption were
      eliminated in MTALs from TLR4(-/-) and myeloid differentiation factor 88 (MyD88)(
      /-) mice but were preserved in MTALs from TIR (Toll/interleukin-1 receptor)
      domain-containing adapter-inducing interferon-beta (Trif)(-/-) mice. Basolateral
      LPS decreased apical Na(+)/H(+) exchanger 3 NHE3 activity through a decrease in
      maximal velocity (V(max)). The inhibition of NHE3 by LPS was eliminated by
      MEK/ERK inhibitors. LPS inhibited HCO(3)(-) absorption despite the presence of
      physiological stimuli that activate ERK in the MTAL. We conclude that basolateral
      LPS inhibits HCO(3)(-) absorption in the MTAL through activation of a
      TLR4/MyD88/MEK/ERK pathway coupled to inhibition of NHE3. These studies identify
      NHE3 as a target of TLR4 signaling in the MTAL and show that bacterial molecules
      can impair the absorptive functions of renal tubules through inhibition of this
      exchanger. The ERK pathway links TLR4 to downstream modulation of ion transport
      proteins and represents a potential target for treatment of sepsis-induced renal
      tubule dysfunction.

PMID- 21881008
TI  - The diving reflex in healthy infants in the first year of life.
AB  - A cohort study was conducted with a random sample of 33 healthy infants evaluated
      at birth and at 1, 2, 3, 4, 5, 6, 9, and 12 months to determine the frequency of
      respiratory rate changes in response to air blown over the face (diving reflex)
      in the first year of life, and to standardize the description of diving reflex
      occurrence. All 33 infants remained neurologically normal throughout follow-up.
      Diving reflex was observed in 95.3% of newborns and in 100% of infants between 2
      and 6 months of age. At 6 months, it started to decrease but persisted in 90% of
      the infants up to 12 months. The diving reflex is highly prevalent in the first
      year of life and can be easily elicited by applying a flow of air over the
      infant's face, particularly during crying.

PMID- 21881010
TI  - Nutrition and traumatic brain injury: a perspective from the Institute of
      Medicine report.

PMID- 21881011
TI  - Psychosocial complaints are associated with venous access-device related
      complications in patients on home parenteral nutrition.
AB  - BACKGROUND: Complications related to venous access devices (VADs) remain the
      major drawback of home parenteral nutrition (HPN) support. In addition to
      technical issues, patients also experience psychosocial problems. The aim of this
      study is to present an overview of VAD-related complications in patients on long
      term HPN and to assess whether these adversities are related to experienced
      psychosocial problems and quality of life (QOL). METHODS: Information on VAD
      related complications was collected from the medical charts of 110 adult HPN
      patients who were followed by the 2 major referral centers in the Netherlands. In
      addition, a survey was conducted in this group to characterize psychosocial
      problems and assess their association with technique-related complications; 75
      patients (68%) responded. RESULTS: At the time of survey, the majority of
      patients (76%) had developed 1 or more episodes of catheter-related sepsis at
      some point during their HPN treatment. The overall incidence of VAD-related blood
      stream infections (BSIs) was 3 per 1,000 venous access days. The incidence of VAD
      occlusions was 0.8 per 1,000 venous access days. During the observation period,
      there was a highly significant association between the incidence of VAD-related
      complications and the occurrence of psychosocial complaints (eg, depression,
      fatigue, social impairment, and decreased QOL). CONCLUSIONS: Psychosocial
      complaints are associated with previously experienced VAD-related complications
      in patients on HPN therapy. Although only an association, and not a causal
      relationship is demonstrated by these findings, our results underscore the need
      for preventive and therapeutic measures regarding both types of problems in these
      patients.

PMID- 21881012
TI  - "CAN WE FEED?" A mnemonic to merge nutrition and intensive care assessment of the
      critically ill patient.
AB  - As care of the critically ill patient grows more complex, so does the breadth of
      knowledge required of the intensivist to deliver quality service. Nutrition is
      one area of many where the complexity of care has grown and the opportunity for
      improving patient outcomes has become evident. The use of mnemonics has proven
      successful in compartmentalizing information that must be considered in complex
      decision-making processes. The authors propose one such mnemonic, "CAN WE FEED?"
      to assist in the development and initiation of early enteral nutrition therapy in
      the intensive care unit (ICU). Critical illness severity (C), age (A), and
      nutrition risk screening (N) are considered when performing a baseline evaluation
      of the critically ill patient upon presentation to the ICU. Wait for
      resuscitation (W) is a key component in the care of most critically ill patients
      and is an important consideration prior to the initiation of feeding. Energy
      requirements (E) are determined using conventional weight-based equations,
      indirect calorimetry, or combinations of both techniques. The more practical
      aspects of support that follow include formula selection (F), enteral access (E),
      efficacy (E), and the determination of tolerance (D). With careful consideration
      of these components through the use of the mnemonic "CAN WE FEED?" the
      intensivist can successfully implement a nutrition plan, and the clinical
      nutritionist can appreciate where nutrition therapy appropriately intervenes in
      the initial resuscitation and management of the critically ill patient.

PMID- 21881013
TI  - Obesity--a growing frontier in nutrition support.

PMID- 21881014
TI  - Obesity epidemic: overview, pathophysiology, and the intensive care unit
      conundrum.
AB  - Obesity is one of the leading causes of preventable death in the United States,
      second only to smoking. The annual number of deaths attributed to obesity is
      estimated to be as high as 400,000. Nearly 70% of the adult U.S. population is
      overweight or obese. The historical viewpoint toward obesity has deemed it to be
      a lifestyle choice or characterological flaw. However, given the emerging
      research into the development of obesity and its related complications, our
      perspective is changing. It is now clear that obesity is a heterogeneous disease
      with many different subtypes, which involves an interplay between genetic and
      environmental factors. The current epidemic of obesity is the result of an
      obesogenic environment (which includes energy-dense foods and a lack of physical
      activity) in individuals who have a genetic susceptibility for developing
      obesity. The pathophysiology associated with weight gain is much more complex
      than originally thought. The heterogeneous nature of the disease makes the
      development of treatment strategies for obesity difficult. Obesity in general is
      associated with increased all-cause mortality and cause-specific mortality (from
      cardiovascular, diabetic, hepatic, and neoplastic causes). Yet despite increased
      overall mortality rates, current evidence suggests that when these same patients
      are admitted to the intensive care unit (ICU), the obesity provides some
      protection against mortality. At present, there is no clear explanation for this
      obesity conundrum in critical illness.

PMID- 21881015
TI  - The outcomes of obese patients in critical care.
AB  - The severity and prevalence of obesity continue to rise throughout the world. A
      similar rise in the prevalence of obesity is seen in the population of patients
      admitted to the intensive care unit (ICU). In the ICU setting, nearly every
      aspect of care is made more difficult by obesity. This review highlights the
      challenges in the care of obese ICU patients. Multiple statistical reviews have
      suggested improved outcomes for obese ICU patients. This article critically
      evaluates published outcome studies and highlights potential confounders that may
      result in misleading results. Body mass index (BMI) has been traditionally used
      to stratify risk in obese populations. Other factors that may be more predictive
      of poor outcomes in obese populations are further discussed. Further research in
      these factors has the potential to guide therapy in high-risk critically ill
      obese populations.

PMID- 21881017
TI  - Issues involved in the process of developing a medical food.
AB  - The creation of a medical food with potential health benefits for a particular
      patient population is a surprisingly complex process. Fortunately, the
      developmental process for a specific medical food is not as rigorous or as
      tightly regulated as that of a pharmaceutical agent. However, numerous factors
      unique to the enteral formulation of a new product come into play, such as
      physical/chemical compatibility, pH, stability, bioavailability, decay, and even
      palatability. Additional considerations such as strength of health benefit
      claims, packaging or presentation, and marketability determine the ultimate
      commercialization and whether a product ends up being released to the public. A
      full understanding of the development, substantiation, and commercialization of a
      medical food is necessary for important physiologic concepts in nutrition therapy
      to end up as part of the therapeutic regimen at the bedside of the critically ill
      obese patient.

PMID- 21881016
TI  - Pharmaconutrition for the obese, critically ill patient.
AB  - Obesity is an epidemic that affects approximately 30% of the adult population in
      the United States. The prevalence of obesity in the critically ill seems to
      correlate with the rise in obesity in the general population. Delivery of
      standard enteral nutrition (EN) to patients in the intensive care unit (ICU) has
      been shown to decrease infectious complications. Obese ICU patients may be at
      increased risk for infections, ICU length of stay, and ventilation requirements
      compared to the nonobese. Pharmaconutrition has been shown to decrease many of
      these negative ICU outcomes. Because of obesity-associated increased ICU risk,
      provision of certain pharmaconutrients should be considered in obese patients
      requiring EN therapy. This review examines the evidence for specific nutrients
      such as green tea, curcumin, sulforaphane, poly-unsaturated fatty acids, L
      arginine, L-citrulline, L-leucine, protein, probiotics, magnesium, medium-chain
      triglycerides, and zinc for the treatment of obesity. These nutrients could
      potentially be added to current EN formulas or provided as supplements.

PMID- 21881018
TI  - Nutrition delivery for obese ICU patients: delivery issues, lack of guidelines,
      and missed opportunities.
AB  - The most appropriate enteral formula for the severely obese population has yet to
      be determined. The obese patient in the intensive care unit (ICU) creates
      numerous difficulties for managing care, one being the ability to deliver
      appropriate and timely nutrition. Access for nutrition therapy, either enteral or
      parenteral, can also create a challenge. Currently, no specific guidelines are
      available on a national or international scale to address the issues of how and
      when to feed the obese patient in the ICU. A bias against feeding these patients
      exists, secondary to the perception that an enormous quantity of calories is
      stored in adipose tissue. Making a specialty enteral formula for obesity from
      existing commercial formulas and other modular nutrient components is not
      practical, secondary to difficulty with solubility issues, dilution of the
      formula, and safety concerns. Using today's concepts and current metabolic data,
      a formula could be produced that would address many of the specific metabolic
      derangements noted in obesity. This formula should have a high-protein, low
      carbohydrate content with at least a portion of the lipid source coming from fish
      oil. Specific nutrients that may be beneficial in obesity include arginine,
      glutamine, leucine, L-carnitine, lipoic acid, S-adenosylmethionine, and betaine.
      Certain trace minerals such as magnesium, zinc, and selenium may also be of value
      in the obese population. The concept of a specific bariatric formulation for the
      ICU setting is theoretically sound, is scientifically based, and could be
      delivered to patients safely.

PMID- 21881019
TI  - Nutrition therapy of the severely obese, critically ill patient: summation of
      conclusions and recommendations.
AB  - This report compiles the conclusions and recommendations for nutrition therapy of
      the obese, critically ill patient derived by the group of experts participating
      in this workshop on obesity in critical care nutrition. The recommendations are
      based on consensus opinions of the group after review of the current literature.
      Obesity clearly adds to the complexity of nutrition therapy in the intensive care
      unit (ICU). Obesity alters the incidence and severity of comorbidities, tolerance
      of the prescribed regimen, and ultimately patient outcome through the course of
      hospitalization. Although the basic principles of critical care nutrition apply
      to the obese ICU patient, a high-protein, hypocaloric regimen should be provided
      to reduce the fat mass, improve insulin sensitivity, and preserve lean body mass.
      The ideal enteral formula should have a low nonprotein calorie to nitrogen ratio
      and have a variety of pharmaconutrient agents added to modulate immune responses
      and reduce inflammation.

PMID- 21881020
TI  - Effects of hot-iron branding on heart rate, breathing rate and behaviour of
      anaesthetised Steller sea lions.
AB  - This study assessed the heart rate, breathing rate and behavioural responses of
      12 juvenile Steller sea lions during hot-iron branding under isoflurane
      anaesthesia. Physiological and behavioural measures were recorded in four
      periods: baseline (five minutes), sham branding (one minute), branding
      (approximately 2.7 minutes) and postbranding (five minutes). No difference in
      heart rate was noted from baseline to sham branding, but heart rate increased
      from mean (sem) 78.3 (2.4) bpm in the baseline period to 85.6 (2.5) bpm in the
      branding period. Heart rate remained elevated in the postbranding period,
      averaging 84.7 (2.5) bpm. Breathing rate averaged 2.5 (1.0) breaths/minute in the
      baseline and sham branding periods increased to 8.9 (1.0) breaths/minute during
      branding, but returned to baseline by the postbranding period. Behaviourally,
      half of the sea lions exhibited trembling and head and shoulder movements during
      branding.

PMID- 21881021
TI  - Successful control of infectious laryngotracheitis on a multiage laying hen farm.

PMID- 21881022
TI  - The British pig health schemes: integrated systems for large-scale pig abattoir
      lesion monitoring.
AB  - Pig health schemes based on abattoir inspections provide an integrated system to
      optimise the postmortem detection and the reporting of pathological lesions. In
      Great Britain, two initiatives have been implemented by the pig industry:
      Wholesome Pigs Scotland (WPS) and the BPEX Pig Health Scheme (BPHS). These
      schemes record the presence of a range of pathological lesions detected by means
      of detailed inspection of the pluck and the skin of the slaughtered pigs. The
      lesions are those associated with a reduction in performance traits or are
      indicators of animal welfare problems. This paper aims to provide an overview of
      the objectives behind the BPHS and their activities, outlining similarities and
      differences between WPS and BPHS on five main operational topics: the lesions
      monitored, the administration of the schemes, flow of the information, inspection
      strategies and the major idiosyncratic characteristics of the schemes. These
      initiatives inform individual producers and their veterinarians of the occurrence
      of pathological conditions affecting their pig herds. Additionally, they offer
      the added value of providing nationwide disease monitoring information and have
      the potential to be a useful surveillance tool for emerging and enzootic
      conditions.

PMID- 21881023
TI  - Equine multinodular pulmonary fibrosis in horses in the UK.

PMID- 21881024
TI  - Seroprevalence of Coxiella burnetii antibodies in sheep and goats in the Republic
      of Ireland.

PMID- 21881025
TI  - Effects of parenteral amoxicillin on recovery rates and new infection rates for
      contagious ovine digital dermatitis in sheep.
AB  - The present study is a randomised split-flock treatment trial, which compared the
      effect of foot bathing in a 1 per cent solution of chlortetracycline alone with a
      treatment protocol that added a single injection of a long-acting amoxicillin.
      Overall, the prevalence of contagious ovine digital dermatitis in the examined
      flock was 22 per cent, while 45.7 per cent of affected sheep had infections in
      two or more feet. Parenteral antibiotic treatment increased the odds of a
      recovery by 3.8 times (95 per cent confidence interval 1.05 to 14.0) (P=0.008).
      Moreover, the amoxicillin injection may also have had a preventative effect,
      reducing the rate of establishment of new infections from 2.5 per cent for foot
      bathing alone compared with 1.0 per cent with the addition of parenteral
      amoxicillin.

PMID- 21881026
TI  - Body fatness during childhood and adolescence, adult height, and risk of
      colorectal adenoma in women.
AB  - The latest report by the World Cancer Research Fund/American Institute of Cancer
      Research concluded that there is convincing evidence that adult height and
      obesity are risk factors for colorectal cancer. However, studies relating body
      fatness during early life to the risk of colorectal cancer or adenoma are scarce.
      In the Nurses' Health Study II, participants recalled adult attained height and
      body shape at ages 5, 10, and 20 years (using a 9-level pictogram: 1 = most lean
      body shape, 9 = most overweight body shape) at baseline. Among 32,707 women who
      had at least one lower bowel endoscopy between 1991 and 2005, 2,327 colorectal
      adenomas were documented. Adult height was positively associated with risk of
      colorectal adenoma (multivariate OR per 2 inch increment 1.05, 95% CI: 1.01
      1.09). Comparing women who were overweight (body shape level 6 or higher) to
      women who were most lean (body shape level 1), ORs (95% CI, P(trend)) of
      colorectal adenoma for body shapes at ages 5, 10, and 20 years were 1.44 (1.04
      1.99, 0.01), 1.21 (0.93-1.56, 0.05), and 1.03 (0.74-1.42, 0.58), respectively.
      Adjustment for adult body mass index did not change results substantially. The
      positive associations for body fatness at ages 5 and 10 years as well as adult
      height were restricted to distal adenoma, while not seen for proximal or rectal
      adenoma. Higher height and body fatness during childhood was associated with
      increased risk of distal adenoma later in life, independent of adult body weight.

PMID- 21881027
TI  - Ethanol promotes chemically induced oral cancer in mice through activation of the
      5-lipoxygenase pathway of arachidonic acid metabolism.
AB  - Alcohol drinking is a known risk factor for oral cancer in humans. However,
      previous animal studies on the promoting effect of ethanol on oral carcinogenesis
      were inconclusive. It is necessary to develop an animal model with which the
      molecular mechanism of ethanol-related oral carcinogenesis may be elucidated to
      develop effective prevention strategies. In this study, mice were first treated
      with 4-nitroquinoline-1-oxide (4NQO, 100 MUg/mL in drinking water) for 8 weeks
      and then given water or ethanol (8%) as the sole drink for another 16 weeks.
      During the experiment, 8% ethanol was well tolerated by mice. The incidence of
      squamous cell carcinoma (SCC) increased from 20% (8/41) to 43% (17/40; P < 0.05).
      Expression of 5-lipoxygenase (5-Lox) and cyclooxygenase 2 (Cox-2) was increased
      in dysplasia and SCC of 4NQO-treated tongues and further enhanced by ethanol.
      Using this mouse model, we further showed that fewer cancers were induced in
      Alox5(-/-) mice, as were cell proliferation, inflammation, and angiogenesis in
      the tongue, as compared with Alox5(+/+) mice. Interestingly, Cox-2 expression was
      induced by ethanol in knockout mice, whereas 5-Lox and leukotriene A4 hydrolase
      (LTA4H) expression and leukotriene B4 (LTB4) biosynthesis were dramatically
      reduced. Moreover, ethanol enhanced expression and nuclear localization of 5-Lox
      and stimulated LTB4 biosynthesis in human tongue SCC cells (SCC-15 and SCC-4) in
      vitro. In conclusion, this study clearly showed that ethanol promoted 4NQO
      induced oral carcinogenesis, at least in part, through further activation of the
      5-Lox pathway of arachidonic acid metabolism.

PMID- 21881028
TI  - Mechanistic contribution of ubiquitous 15-lipoxygenase-1 expression loss in
      cancer cells to terminal cell differentiation evasion.
AB  - Loss of terminal cell differentiation promotes tumorigenesis. 15-Lipoxygenase-1
      (15-LOX-1) contributes to terminal cell differentiation in normal cells. The
      mechanistic significance of 15-LOX-1 expression loss in human cancers to terminal
      cell differentiation suppression is unknown. In a screen of 128 cancer cell lines
      representing more than 20 types of human cancer, we found that 15-LOX-1 mRNA
      expression levels were markedly lower than levels in terminally differentiated
      cells. Relative expression levels of 15-LOX-1 (relative to the level in
      terminally differentiated primary normal human-derived bronchial epithelial
      cells) were lower in 79% of the screened cancer cell lines than relative
      expression levels of p16 (INK4A), which promotes terminal cell differentiation
      and is considered one of the most commonly lost tumor suppressor genes in cancer
      cells. 15-LOX-1 was expressed during terminal differentiation in three
      dimensional air-liquid interface cultures, and 15-LOX-1 expression and terminal
      differentiation occurred in immortalized nontransformed bronchial epithelial but
      not in lung cancer cell lines. 15-LOX-1 expression levels were lower in human
      tumors than in paired normal lung epithelia. Short hairpin RNA-mediated
      downregulation of 15-LOX-1 in Caco-2 cells blocked enterocyte-like
      differentiation, disrupted tight junction formation, and blocked E-cadherin and
      ZO-1 localization to the cell wall membrane. 15-LOX-1 episomal expression in Caco
      2 and HT-29 colon cancer cells induced differentiation. Our findings indicate
      that 15-LOX-1 downregulation in cancer cells is an important mechanism for
      terminal cell differentiation dysregulation and support the potential therapeutic
      utility of 15-LOX-1 reexpression to inhibit tumorigenesis.

PMID- 21881029
TI  - Cryptotanshinone inhibits lymphatic endothelial cell tube formation by
      suppressing VEGFR-3/ERK and small GTPase pathways.
AB  - Cryptotanshinone (CPT), isolated from the plant Salvia miltiorrhiza Bunge, is a
      potential anticancer agent. However, the underlying mechanism remains to be
      defined. Here, we show that CPT inhibited lymphangiogenesis in an in vitro model
      (tube formation). This effect was partly attributed to inhibiting expression of
      VEGF receptor 3 (VEGFR-3) in murine lymphatic endothelial cells (LEC), as
      overexpression of VEGFR-3 conferred resistance to CPT inhibition of the tube
      formation, whereas downregulation of VEGFR-3 mimicked the effect of CPT, blocking
      the tube formation. Furthermore, CPT inhibited phosphorylation of the
      extracellular signal-related kinase 1/2 (ERK1/2). Overexpression of VEGFR-3
      attenuated CPT inhibition of ERK1/2 phosphorylation, whereas downregulation of
      VEGFR-3 inhibited ERK1/2 phosphorylation in LECs. Expression of constitutively
      active MKK1 resulted in activation of ERK1/2 and partially prevented CPT
      inhibition of LEC tube formation. In addition, CPT also inhibited protein
      expression and activities of Rac1 and Cdc42 but not RhoA. Expression of
      constitutively active Rac1 and Cdc42 concurrently, but not Rac1 or Cdc42 alone,
      conferred resistance to CPT inhibition of LEC tube formation. Taken together, the
      results suggest that CPT inhibits LEC tube formation, in part, by inhibiting
      VEGFR-3-mediated ERK1/2 phosphorylation and, in part, by inhibiting expression of
      the small GTPases.

PMID- 21881030
TI  - A randomized controlled trial of celecoxib to prevent recurrence of nonmuscle
      invasive bladder cancer.
AB  - Significant morbidity and expense result from frequent recurrences of nonmuscle
      invasive bladder cancer (NMIBC) after standard treatment, and carcinoma in situ
      (Tis) is a poor prognostic factor. Predicated on observational and preclinical
      data strongly supporting cyclooxygenase-2 (COX-2) in the pathogenesis, and the
      activity of COX-2 inhibitors, in bladder cancer, we conducted a randomized,
      double-blind, placebo-controlled trial to determine whether celecoxib could
      reduce the time-to-recurrence (TTR) in NMIBC patients at high risk for
      recurrence. A total of 146 patients were randomized to celecoxib (200 mg) or
      placebo orally twice daily for at least 12 months. The average treatment duration
      was 1.25 years. Primary intent-to-treat analysis revealed celecoxib did not
      statistically significantly prolong TTR compared with placebo (P = 0.17, log
      rank) with a median follow-up of 2.49 years. The recurrence-free rate at 12
      months with celecoxib was 88% (95% CI: 0.81-0.96) versus 78% (95% CI: 0.69-0.89)
      with placebo. After controlling for covariates with Cox regression analysis,
      recurrence rates did not differ between the two study arms (HR = 0.69; 95% CI:
      0.37-1.29). However, celecoxib had a marginally significant effect on reducing
      metachronous recurrences (vs. placebo) with HR of 0.56 (95% CI: 0.3-1.06; P =
      0.075). Celecoxib was well tolerated, with similar adverse events and quality-of
      life in both arms. Our clinical trial results do not show a clinical benefit for
      celecoxib in preventing NMIBC recurrence but further investigation of COX-2
      inhibitors in this setting is warranted.

PMID- 21881031
TI  - Transient elevation of international normalized ratio during cisplatin-based
      chemotherapy in patients who are taking warfarin.
AB  - OBJECTIVE: To report 2 cases of a probable interaction between cisplatin and
      warfarin. CASE SUMMARY: Two cases of transient elevation of international
      normalized ratio (INR) during irinotecan (60 mg/m2 on days 1, 8, and 15) plus
      cisplatin (60 mg/m2 on day 1) chemotherapy with concomitant warfarin are
      presented. In both cases, warfarin dosages were stable at the therapeutic target
      range prior to initiation of chemotherapy. Granisetron hydrochloride (3 mg on
      days 1, 8, and 15) and dexamethasone (13.2 mg on day 1 and 6.6 mg on days 2, 3,
      8, and 15) were used prior to irinotecan administration in both patients. In
      addition, aprepitant was administered to both patients for 3-5 days with
      cisplatin. One of these patients also received aprepitant with irinotecan on days
      8 and 15. During chemotherapy, INR was transiently elevated almost 1.5-fold over
      baseline level on day 3. This variation did not occur in subsequent irinotecan
      cycles on days 8 and 15. The timing of these increases was similar in each of the
      cycles. DISCUSSION: Cisplatin was the common drug in the cases presented and
      therefore could be related to the INR elevations. To our knowledge, these are the
      first reports of an interaction between warfarin and irinotecan-cisplatin
      chemotherapy, but reports of a similar interaction with chemotherapy including
      platinum derivatives exist. Use of the Horn Drug Interaction Probability Scale
      indicated a probable interaction between warfarin and cisplatin. CONCLUSIONS:
      Cisplatin might affect the anticoagulation function of warfarin. Careful INR
      monitoring is necessary during antineoplastic chemotherapy with cisplatin in
      patients taking warfarin.

PMID- 21881032
TI  - Bivalirudin dosing adjustments for reduced renal function with or without
      hemodialysis in the management of heparin-induced thrombocytopenia.
AB  - BACKGROUND: While not approved by the Food and Drug Administration for treatment
      of heparin-induced thrombocytopenia (HIT), except in patients undergoing
      percutaneous interventions, the direct thrombin inhibitor bivalirudin is a
      treatment option that is gaining use. An initial dose of bivalirudin 0.15-0.2
      mg/kg/h, adjusted to an activated partial thromboplastin time (aPTT) of 1.5-2.5
      times the baseline value, has been suggested. Initial dosing in patients with
      renal dysfunction, including those on hemodialysis, is unclear. OBJECTIVE: To
      evaluate initial bivalirudin dosing requirements in patients with and without
      renal dysfunction, including patients on different forms of dialysis. METHODS: A
      retrospective analysis of 135 patients treated with bivalirudin for HIT between
      June 2004 and October 2009 was conducted at a tertiary care medical center. The
      patients were divided into groups, based on renal function. Patients receiving
      dialysis were divided into 3 subgroups based on the mode of hemodialysis:
      intermittent hemodialysis (IHD, n = 24), sustained low-efficiency daily
      diafiltration (SLEDD, n = 12), or continuous renal replacement therapy (CRRT, n =
      5). Patients not receiving dialysis were separated into 3 subgroups based on
      calculated creatinine clearance (CrCl): CrCl >60 mL/min (n = 52), CrCl 30-60
      mL/min (n = 26), and CrCl <30 mL/min (n = 16). RESULTS: Compared with patients
      with normal renal function (CrCl >60 mL/min), patients with differing degrees of
      renal dysfunction (CrCl 30-60 and <30 mL/min) required lower doses of bivalirudin
      to achieve aPTT goal (0.13 vs 0.08 vs 0.05 mg/kg/h, respectively; p < 0.001).
      Patients on dialysis (IHD, SLEDD, CRRT) also required dose reductions (0.07,
      0.09, and 0.07 mg/kg/h) compared with patients with normal renal function, but
      higher dosing requirements than patients not receiving dialysis with CrCl <30
      mL/min. CONCLUSIONS: Patients with renal dysfunction require a reduced dose of
      bivalirudin to reach a therapeutic aPTT goal. Slightly higher doses may be
      observed in patients receiving hemodialysis.

PMID- 21881033
TI  - Hereditary neuropathy unmasked by levofloxacin.

PMID- 21881034
TI  - Drug-induced exanthem following dabigatran.
AB  - OBJECTIVE: To report an incident of a drug-induced exanthem during treatment with
      dabigatran in a patient without prior exposure to the drug. CASE SUMMARY: A 20
      year-old white male was prescribed oral dabigatran 150 mg twice daily for
      thromboembolic prevention because of nonvalvular atrial fibrillation. After 2
      weeks of dabigatran therapy, a raised, pruritic, erythematous rash developed on
      the patient's inner thigh and forearm. Upon discontinuation of dabigatran and
      initiation of oral corticosteroid treatment, the rash resolved. Dabigatran
      therapy was not readministered and thromboembolic prevention therapy with
      warfarin was instituted. DISCUSSION: The clinical evidence for efficacy of
      dabigatran was derived largely from the RE-LY trial, which provided an open-label
      comparison with warfarin for the reduction of stroke and systemic embolism in
      nonvalvular atrial fibrillation. The most frequent adverse reactions leading to
      discontinuation of dabigatran were bleeding and gastrointestinal events. In the
      RE-LY study, drug hyper-sensitivity, allergic edema, anaphylactic reaction, and
      anaphylactic shock were reported in <0.1% of patients receiving dabigatran.
      Despite the low incidence of hypersensitivity reported in the RE-LY trial, the
      use of the Naranjo probability scale indicated a probable relationship between
      the rash and dabigatran therapy in this patient. CONCLUSIONS: Upon initiation of
      dabigatran therapy, surveillance for hyper-sensitivity reactions should be
      included as part of routine drug monitoring.

PMID- 21881035
TI  - StatBite. Smoking rates in the U.K.

PMID- 21881036
TI  - The new image of tobacco smoking.

PMID- 21881037
TI  - The U.S. plays catch up.

PMID- 21881038
TI  - Early-stage progress on glioma vaccines.

PMID- 21881039
TI  - Elucidating an uncommon disease: inflammatory breast cancer.

PMID- 21881040
TI  - U.N. meeting to address growing burden of noncommunicable diseases.

PMID- 21881041
TI  - Do all patients with breast cancer require systemic adjuvant therapy?

PMID- 21881042
TI  - Mortality rates among early-stage hormone receptor-positive breast cancer
      patients: a population-based cohort study in Denmark.
AB  - BACKGROUND: Indications for adjuvant endocrine treatment of breast cancer have
      gradually increased over the past several years. We aimed to define subgroups of
      patients who may or may not benefit from adjuvant endocrine therapy. METHODS: A
      population-based cohort of systemically untreated breast cancer patients (N =
      3197) were identified within the registry of the Danish Breast Cancer Cooperative
      Group (DBCG). The patients were node negative and had estrogen receptor-positive
      and/or progesterone receptor-positive tumors (except medullary tumors) and were
      further characterized by the following risk factors: aged 35-74 years (grouped
      into 5-year categories) at surgery, tumor size (<=20 mm), and histopathology
      (grade 1 ductal carcinoma, grade 1 or 2 invasive lobular carcinoma, other or
      unknown histopathology). Standardized mortality ratios (SMRs) were calculated
      based on the mortality rate (observed number of deaths per 100,000 person-years)
      among patients relative to the mortality rate in the general population of women
      (expected number of deaths per 100,000 person-years). The association between
      standardized mortality ratio and risk factors were analyzed in univariate and
      multivariable Poisson regression models. All findings were validated in a
      subsequent DBCG cohort of breast cancer patients (N = 2710). RESULTS: The median
      follow-up after surgery was 14.8 years. In the study population there were 970
      deaths compared with expected death of 737 women, which was an excess mortality
      of 233 deaths (SMR = 1.32, 95% CI = 1.24 to 1.40). Mortality rates were 2356 per
      100,000 person-years in the study population and 1790 per 100,000 person-years in
      the general population of women. The mortality rate was associated with larger
      tumor size (11-20 mm tumors vs 1-10 mm tumors, SMR = 1.42, 95% confidence
      interval [CI] = 1.31 to 1.53 vs. SMR = 1.12, 95% CI = 1.00 to 1.26). The
      mortality rate was also associated with age (35-59 years, SMR > 1) compared with
      that in the general population of age-matched women, except for a small subgroup
      of patients (aged 60-74 years, tumors <=10 mm, grade 1 ductal carcinoma, and
      grade 1 or 2 lobular carcinoma: adjusted relative risk = 1.02, 95% CI = 0.89 to
      1.16.). CONCLUSIONS: A small subgroup of breast cancer patients who were 60 years
      or older and had hormone-responsive early-stage tumors up to 10 mm, and received
      no systemic adjuvant therapy, were not at increased risk of mortality compared
      with women in this age-group in the general population.

PMID- 21881043
TI  - Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult
      onset familial HLH.
AB  - Familial hemophagocytic lymphohistiocytosis (HLH) is a rare primary
      immunodeficiency disorder characterized by defects in cell-mediated cytotoxicity
      that results in fever, hepatosplenomegaly, and cytopenias. Familial HLH is well
      recognized in children but rarely diagnosed in adults. We conducted a
      retrospective review of genetic and immunologic test results in patients who
      developed HLH in adulthood. Included in our study were 1531 patients with a
      clinical diagnosis of HLH; 175 patients were 18 years or older. Missense and
      splice-site sequence variants in PRF1, MUNC13-4, and STXBP2 were found in 25
      (14%) of the adult patients. The A91V-PRF1 genotype was found in 12 of these
      patients (48%). The preponderance of hypomorphic mutations in familial HLH
      causing genes correlates with the later-onset clinical symptoms and the more
      indolent course in adult patients. We conclude that late-onset familial HLH
      occurs more commonly than was suspected previously.

PMID- 21881044
TI  - Critical role for Syk in responses to vascular injury.
AB  - Although current antiplatelet therapies provide potent antithrombotic effects,
      their efficacy is limited by a heightened risk of bleeding and failure to affect
      vascular remodeling after injury. New lines of research suggest that thrombosis
      and hemorrhage may be uncoupled at the interface of pathways controlling
      thrombosis and inflammation. Here, as one remarkable example, studies using a
      novel and highly selective pharmacologic inhibitor of the spleen tyrosine kinase
      Syk [PRT060318; 2-((1R,2S)-2-aminocyclohexylamino)-4-(m-tolylamino)pyrimidine-5
      carboxamide] coupled with genetic experiments, demonstrate that Syk inhibition
      ameliorates both the acute and chronic responses to vascular injury without
      affecting hemostasis. Specifically, lack of Syk (murine radiation chimeras)
      attenuated shear-induced thrombus formation ex vivo, and PRT060318 strongly
      inhibited arterial thrombosis in vivo in multiple animal species while having
      minimal impact on bleeding. Furthermore, leukocyte-platelet-dependent responses
      to vascular injury, including inflammatory cell recruitment and neointima
      formation, were markedly inhibited by PRT060318. Thus, Syk controls acute and
      long-term responses to arterial vascular injury. The therapeutic potential of Syk
      may be exemplary of a new class of antiatherothrombotic agents that target the
      interface between thrombosis and inflammation.

PMID- 21881046
TI  - Gene mutation patterns and their prognostic impact in a cohort of 1185 patients
      with acute myeloid leukemia.
AB  - To evaluate the prognostic value of genetic mutations for acute myeloid leukemia
      (AML) patients, we examined the gene status for both fusion products such as AML1
      (CBFalpha)-ETO, CBFbeta-MYH11, PML-RARalpha, and MLL rearrangement as a result of
      chromosomal translocations and mutations in genes including FLT3, C-KIT, N-RAS,
      NPM1, CEBPA, WT1, ASXL1, DNMT3A, MLL, IDH1, IDH2, and TET2 in 1185 AML patients.
      Clinical analysis was mainly carried out among 605 cases without recognizable
      karyotype abnormalities except for 11q23. Of these 605 patients, 452 (74.7%) were
      found to have at least 1 mutation, and the relationship of gene mutations with
      clinical outcome was investigated. We revealed a correlation pattern among NPM1,
      DNMT3A, FLT3, IDH1, IDH2, CEBPA, and TET2 mutations. Multivariate analysis
      identified DNMT3A and MLL mutations as independent factors predicting inferior
      overall survival (OS) and event-free survival (EFS), whereas biallelic CEBPA
      mutations or NPM1 mutations without DNMT3A mutations conferred a better OS and
      EFS in both the whole group and among younger patients < 60 years of age. The use
      of molecular markers allowed us to subdivide the series of 605 patients into
      distinct prognostic groups with potential clinical relevance.

PMID- 21881047
TI  - Predictors of greater than 80% 2-year mortality in primary myelofibrosis: a Mayo
      Clinic study of 884 karyotypically annotated patients.
AB  - DIPSS-plus (the Dynamic International Prognostic Scoring System-plus) includes 8
      risk factors for survival in primary myelofibrosis. In the present study of 884
      karyotypically annotated patients with primary myelofibrosis, we sought to
      identify 1 or 2 parameters that can reliably predict death in the first 2 years
      of disease. After a median of 8.2 years from time of referral to the Mayo Clinic,
      564 deaths (64% of patients in the study) had been recorded. Risk factors
      associated with > 80% 2-year mortality included monosomal karyotype,
      inv(3)/i(17q) abnormalities, or any 2 of the following: circulating blasts > 9%,
      leukocytes >= 40 * 10(9)/L, or other unfavorable karyotype. Patients with any 1
      of these risk profiles (n = 52) displayed significantly shorter overall survival
      than those otherwise belonging to a high-risk category per DIPSS-plus (n = 298);
      respective median survivals were 9 and 23 months (hazard ratio 2.2, 95%
      confidence interval 1.6-3.1; P < .01). The present information complements DIPSS
      plus in the selection of primary myelofibrosis patients for high-risk treatment
      approaches.

PMID- 21881045
TI  - Regulatory T cells in acute myelogenous leukemia: is it time for
      immunomodulation?
AB  - The microenviroment of acute myelogenous leukemia (AML) is suppressive for immune
      effector cells. Regulatory T cells (Tregs) have been recognized as a contributor
      factor and may be recruited and exploited by leukemic cells to evade
      immunesurveillance. Studies have shown that the frequencies of marrow and blood
      Tregs are greater in patients with AML than in control patients. Although
      increased Tregs have been associated with a decreased risk of GVHD after
      allogeneic HCT and hence may impede the graft-versus-tumor effect, recent
      findings indicate that that this may not be the case. Because there is a need to
      improve outcomes of standard treatment (chemotherapy with or without allogeneic
      HCT) in AML, targeting Tregs present an outstanding opportunity in AML because
      discoveries may apply throughout its treatment. Here, we review data on the roles
      of Tregs in mediating immune system-AML interactions. We focused on in vitro,
      animal, and observational human studies of Tregs in AML biology, development,
      prognosis, and therapy in different settings (eg, vaccination and HCT).
      Manipulation of Tregs or other types of immunomodulation may become a part of AML
      treatment in the future.

PMID- 21881048
TI  - Alteration of BIRC3 and multiple other NF-kappaB pathway genes in splenic
      marginal zone lymphoma.
AB  - Splenic marginal zone lymphoma (SMZL) is one of the few B-cell lymphoma types
      that remain orphan of molecular lesions in cancer-related genes. Detection of
      active NF-kappaB signaling in 14 (58%) of 24 SMZLs prompted the investigation of
      NF-kappaB molecular alterations in 101 SMZLs. Mutations and copy number
      abnormalities of NF-kappaB genes occurred in 36 (36%) of 101 SMZLs and targeted
      both canonical (TNFAIP3 and IKBKB) and noncanonical (BIRC3, TRAF3, MAP3K14) NF
      kappaB pathways. Most alterations were mutually exclusive, documenting the
      existence of multiple independent mechanisms affecting NF-kappaB in SMZL. BIRC3
      inactivation in SMZL recurred because of somatic mutations that disrupted the
      same RING domain that in extranodal marginal zone lymphoma is removed by the
      t(11;18) translocation, which points to BIRC3 disruption as a common mechanism
      across marginal zone B-cell lymphomagenesis. Genetic lesions of NF-kappaB provide
      a molecular basis for the pathogenesis of more than 30% of SMZLs and offer a
      suitable target for NF-kappaB therapeutic approaches in this lymphoma.

PMID- 21881049
TI  - The risk of subsequent cancer and arterial cardiovascular events in patients with
      superficial vein thrombosis in the legs.
AB  - Although it has been clearly demonstrated that venous thromboembolism is
      associated with an increased risk of subsequent overt cancer and arterial
      cardiovascular events in comparison with control populations, whether this
      association also applies to patients with isolated (ie, without concomitant
      involvement of the deep vein system) superficial vein thrombosis (SVT) in the
      legs is unknown. In 737 consecutive patients with isolated SVT not involving the
      sapheno-femoral junction, we conducted a retrospective investigation to assess
      the rate of cancer and that of arterial cardiovascular events occurring during
      follow-up. The event rates were compared with those occurring in 1438 controls
      having comparable characteristics. Both cases and controls were followed-up for
      an average period of 26 +/- 8 months (range, 3-45). Malignancy was diagnosed in
      26 cases (3.5%) and 56 controls (3.9%), leading to a hazard ratio of 0.86 (95%
      confidence interval, 0.55%-1.35%). Arterial cardiovascular events occurred in 32
      cases (4.3%) and 63 controls (4.4%), leading to a hazard ratio of 0.97 (95%
      confidence interval, 0.63%-1.50%). We conclude that the occurrence of isolated
      SVT in the legs does not place patients at an increased risk of malignancies or
      arterial cardiovascular events. Whether this conclusion also applies to patients
      whose thrombosis involves the sapheno-femoral junction remains to be
      demonstrated.

PMID- 21881050
TI  - The utility of plasma vascular endothelial growth factor levels in the diagnosis
      and follow-up of patients with POEMS syndrome.
AB  - The POEMS syndrome is associated with elevated vascular endothelial growth factor
      (VEGF) levels. Several studies have compared serum VEGF levels between POEMS
      patients and other disease entities showing higher serum VEGF in POEMS syndrome;
      however, it is unknown whether serum levels are reliable and reproducible given
      variable platelet release of VEGF. We therefore compared plasma levels of VEGF in
      29 patients with POEMS syndrome with those of other disorders (n = 76). We
      demonstrated that plasma VEGF levels are useful in differentiating POEMS from
      other plasma cell dyscrasias, neuropathic processes, and multisystem illnesses.
      Plasma VEGF is also useful in monitoring disease activity after treatment and
      correlates with clinical improvements better than hematologic response.

PMID- 21881051
TI  - Site-specific gene correction of a point mutation in human iPS cells derived from
      an adult patient with sickle cell disease.
AB  - Human induced pluripotent stem cells (iPSCs) bearing monogenic mutations have
      great potential for modeling disease phenotypes, screening candidate drugs, and
      cell replacement therapy provided the underlying disease-causing mutation can be
      corrected. Here, we report a homologous recombination-based approach to precisely
      correct the sickle cell disease (SCD) mutation in patient-derived iPSCs with 2
      mutated beta-globin alleles (beta(s)/beta(s)). Using a gene-targeting plasmid
      containing a loxP-flanked drug-resistant gene cassette to assist selection of
      rare targeted clones and zinc finger nucleases engineered to specifically
      stimulate homologous recombination at the beta(s) locus, we achieved precise
      conversion of 1 mutated beta(s) to the wild-type beta(A) in SCD iPSCs. However,
      the resulting co-integration of the selection gene cassette into the first intron
      suppressed the corrected allele transcription. After Cre recombinase-mediated
      excision of this loxP-flanked selection gene cassette, we obtained "secondary"
      gene-corrected beta(s)/beta(A) heterozygous iPSCs that express at 25% to 40%
      level of the wild-type transcript when differentiated into erythrocytes. These
      data demonstrate that single nucleotide substitution in the human genome is
      feasible using human iPSCs. This study also provides a new strategy for gene
      therapy of monogenic diseases using patient-specific iPSCs, even if the
      underlying disease-causing mutation is not expressed in iPSCs.

PMID- 21881053
TI  - Quality-of-life outcomes in transoral robotic surgery.
AB  - OBJECTIVE: To report long-term, health-related quality-of-life (HRQOL) outcomes
      in patients treated with transoral robotic surgery (TORS). STUDY DESIGN:
      Prospective, longitudinal, clinical study on functional and HRQOL outcomes in
      TORS. SETTING: University tertiary care facility. SUBJECTS AND METHODS: Patients
      who underwent TORS were asked to complete a Head and Neck Cancer Inventory before
      treatment and at 3 weeks and 3, 6, and 12 months postoperatively. Demographic,
      clinicopathological, and follow-up data were collected. RESULTS: Sixty-four
      patients who underwent TORS were enrolled. A total of 113 TORS procedures were
      performed. The mean follow-up time was 16.3 +/- 7.49 months. The HRQOL was
      assessed at 3 weeks and at 3, 6, and 12 months, with a response rate of 78%, 44%,
      41%, and 28%, respectively. TORS was performed most frequently for squamous cell
      carcinoma (88%). There was a decrease from baseline in the speech, eating,
      aesthetic, social, and overall QOL domains immediately after treatment. At the 1
      year follow-up, the HRQOL scores in the aesthetic, social, and overall QOL
      domains were in the high domain. Patients with malignant lesions had
      significantly lower postoperative HRQOL scores in the speech, eating, social, and
      overall QOL domains (P < .05). Patients who underwent adjuvant radiation therapy
      or chemotherapy and radiation therapy had lower postoperative scores in the
      eating, social, and overall QOL domains (P < .05). CONCLUSION: The preliminary
      data show that patients who undergo TORS for malignancies and receive adjuvant
      therapy tend to have lower HRQOL outcomes. TORS is a promising, minimally
      invasive, endoscopic alternative surgical treatment of laryngopharyngeal tumors.

PMID- 21881052
TI  - Latent KSHV infection increases the vascular permeability of human endothelial
      cells.
AB  - Kaposi sarcoma-associated herpesvirus (KSHV) is associated with 3 different human
      malignancies: Kaposi sarcoma (KS), primary effusion lymphoma, and multicentric
      Castleman disease. The KS lesion is driven by KSHV-infected endothelial cells and
      is highly dependent on autocrine and paracrine factors for survival and growth.
      We report that latent KSHV infection increases the vascular permeability of
      endothelial cells. Endothelial cells with latent KSHV infection display increased
      Rac1 activation and activation of its downstream modulator, p21-activated kinase
      1 (PAK1). The KSHV-infected cells also exhibit increases in tyrosine
      phosphorylation of vascular endothelial (VE)-cadherin and beta-catenin, whereas
      total levels of these proteins remained unchanged, suggesting that latent
      infection disrupted endothelial cell junctions. Consistent with these findings,
      we found that KSHV-infected endothelial cells displayed increased permeability
      compared with uninfected endothelial cells. Knockdown of Rac1 and inhibition of
      reactive oxygen species (ROS) resulted in decreased permeability in the KSHV
      infected endothelial cells. We further demonstrate that the KSHV K1 protein can
      activate Rac1. Rac1 was also highly activated in KSHV-infected endothelial cells
      and KS tumors. In conclusion, KSHV latent infection increases Rac1 and PAK1
      activity in endothelial cells, resulting in the phosphorylation of VE-cadherin
      and beta-catenin and leading to the disassembly of cell junctions and to
      increased vascular permeability of the infected endothelial cells.

PMID- 21881054
TI  - Paralysis of a true vocal cord: a rare presentation of thyroid tuberculosis.

PMID- 21881055
TI  - Is the mandibular nerve block passe?
AB  - BACKGROUND: Providing effective pain control is a critical part of dental
      treatment, yet achieving consistently reliable anesthesia in the mandible has
      proved elusive. The traditional inferior alveolar nerve block (IANB) has a high
      failure rate; for example, the failure rate in lateral incisors is 81 percent. As
      a consequence, new approaches and techniques have been developed. The purpose of
      this supplement to The Journal of the American Dental Association is to determine
      whether the mandibular nerve block has become passe. CONCLUSIONS: The high
      failure rate of the IANB can be frustrating for dentists and lead to discomfort
      for the patient during treatment. The reasons for this high failure rate include
      thickness of the cortical plate of bone in adults, thickness of the soft tissue
      at the injection site leading to increased needle deflection, the difficulty of
      locating the inferior alveolar nerve and the possibility of accessory
      innervation. Although the IANB can be unreliable, it is used commonly to provide
      mandibular anesthesia. CLINICAL IMPLICATIONS: Pain control is an essential part
      of dental treatment. Alternative injection techniques and devices that can help
      increase the success rate of mandibular anesthesia are available.

PMID- 21881059
TI  - Fast automatic translation and morphological decomposition in Chinese-English
      bilinguals.
AB  - In this study, we investigated automatic translation from English to Chinese and
      subsequent morphological decomposition of translated Chinese compounds. In two
      lexical decision tasks, Chinese-English bilinguals responded to English target
      words that were preceded by masked unrelated primes presented for 59 ms.
      Unbeknownst to participants, the Chinese translations of the words in each
      critical pair consisted of a fully opaque compound word (i.e., a compound with
      two constituent morphemes that were semantically unrelated to the compound) and a
      monomorphemic word that was either the first or the second morpheme of the
      compound. The data revealed that bilinguals responded faster to English word
      pairs whose Chinese translations repeated the first morpheme than to English word
      pairs whose Chinese translations did not repeat the first morpheme, but no effect
      of hidden second-morpheme repetition was found. This effect of hidden first
      morpheme repetition suggests that participants translated English words to
      Chinese and decomposed the translated compounds into their constituent morphemes.
      Because the primes were presented for only 59 ms, translation and morphological
      decomposition must be fast and automatic.

PMID- 21881058
TI  - The use of the mandibular infiltration anesthetic technique in adults.
AB  - BACKGROUND: The author describes the use of the infiltration anesthetic technique
      to anesthetize mandibular teeth in adults and explores its mechanism of action.
      METHODS: The author reviewed articles describing randomized controlled trials of
      the mandibular infiltration anesthetic technique in healthy participants.
      RESULTS: The author found that using the mandibular infiltration anesthetic
      technique can produce anesthesia in adult mandibular teeth. The success was dose
      dependent and the choice of anesthetic solution was significant; 4 percent
      articaine with 1:100,000 epinephrine was more effective than 2 percent lidocaine
      with 1:100,000 epinephrine. Combining buccal and lingual infiltrations increased
      success in the mandibular incisor region. The success of the mechanism of
      infiltration of anesthetic at the mandibular first molar appeared to depend on
      the mental foramen. CONCLUSIONS: The mandibular infiltration anesthetic technique
      is an effective method of anesthetizing mandibular incisors. Four percent
      articaine with epinephrine appears to be the preferred solution. CLINICAL
      IMPLICATIONS: The choice of anesthetic solution is important when using the
      infiltration anesthetic technique in the adult mandible.

PMID- 21881057
TI  - Periodontal ligament and intraosseous anesthetic injection techniques:
      alternatives to mandibular nerve blocks.
AB  - BACKGROUND: and Overview. The provision of mandibular anesthesia traditionally
      has relied on nerve block anesthetic techniques such as the Halsted, the Gow
      Gates and the Akinosi-Vazirani methods. The authors present two alternative
      techniques to provide local anesthesia in mandibular teeth: the periodontal
      ligament (PDL) injection and the intraosseous (IO) injection. The authors also
      present indications for and complications associated with these techniques.
      CONCLUSIONS: The PDL injection and the IO injection are effective anesthetic
      techniques for managing nerve block failures and for providing localized
      anesthesia in the mandible. CLINICAL IMPLICATIONS: Dentists may find these
      techniques to be useful alternatives to nerve block anesthesia.

PMID- 21881056
TI  - Alternative mandibular nerve block techniques: a review of the Gow-Gates and
      Akinosi-Vazirani closed-mouth mandibular nerve block techniques.
AB  - BACKGROUND: and Overview. The limited success rate of the standard inferior
      alveolar nerve block (IANB) has led to the development of alternative approaches
      for providing mandibular anesthesia. Two techniques, the Gow-Gates mandibular
      nerve block and the Akinosi-Vazirani closed-mouth mandibular nerve block, are
      reliable alternatives to the traditional IANB. The Gow-Gates technique requires
      the patient's mouth to be open wide, and the dentist aims to administer local
      anesthetic just anterior to the neck of the condyle in proximity to the
      mandibular branch of the trigeminal nerve after its exit from the foramen ovale.
      The Akinosi-Vazirani technique requires the patient's mouth to be closed, and the
      dentist aims to fill the pterygomandibular space with local anesthetic.
      CONCLUSION: Both techniques are indicated for any type of dentistry performed in
      the mandibular arch, but they are particularly advantageous when the patient has
      a history of standard IANB failure owing to anatomical variability or accessory
      innervation. CLINICAL IMPLICATIONS: Having the skill to perform these alternative
      anesthetic techniques increases dentists' ability to provide successful local
      anesthesia consistently for all procedures in mandibular teeth.

PMID- 21881060
TI  - When being right is not enough: four-year-olds distinguish knowledgeable
      informants from merely accurate informants.
AB  - Recent evidence demonstrates that children are selective in their social
      learning, preferring to learn from a previously accurate speaker than from a
      previously inaccurate one. We examined whether children assessing speakers'
      reliability take into account how speakers achieved their prior accuracy. In
      Study 1, when faced with two accurate informants, 4- and 5-year-olds (but not 3
      year-olds) were more likely to seek novel information from an informant who had
      previously given the answers unaided than from an informant who had always relied
      on help from a third party. Similarly, in Study 2, 4-year-olds were more likely
      to trust the testimony of an unaided informant over the testimony provided by an
      assisted informant. Our results indicate that when children reach around 4 years
      of age, their selective trust extends beyond simple generalizations based on
      informants' past accuracy to a more sophisticated selectivity that distinguishes
      between truly knowledgeable informants and merely accurate informants who may not
      be reliable in the long term.

PMID- 21881061
TI  - Psychopathic traits and preattentive threat processing in children: a novel test
      of the fearlessness hypothesis.
AB  - We tested the fearlessness hypothesis of psychopathy in an at-risk sample of 88
      preadolescent children. Psychopathy was measured using combined child- and parent
      reported scores on the Antisocial Process Screening Device (APSD). Using a
      continuous-flash-suppression paradigm, we evaluated threat processing at the
      preattentive level for the first time in a study of psychopathy. Scores for the
      APSD Callous/Unemotional factor, which assesses the core affective deficits of
      psychopathy, predicted preattentive face-recognition deficits for fearful faces
      and, to a lesser extent, for disgusted faces. This finding contradicts recent
      suggestions that the fearlessness associated with psychopathy is solely a
      consequence of overt attentional artifacts. Future research should focus on
      preattentive processing of fear in individuals with callous-unemotional traits,
      and on the implications of preattentive-processing deficits for treatment and
      theory development.

PMID- 21881062
TI  - Forensic dentistry and bitemark analysis: sound science or junk science?

PMID- 21881063
TI  - Ethical injections.

PMID- 21881065
TI  - More about evidence-based dentistry.

PMID- 21881064
TI  - Affordable care and evidence-based dentistry.

PMID- 21881066
TI  - The success of endosseous implants in human immunodeficiency virus-positive
      patients receiving antiretroviral therapy: a pilot study.
AB  - BACKGROUND: In a pilot study, the authors aimed to determine the success rate of
      dental implants placed in patients who were positive for human immunodeficiency
      virus (HIV) and were receiving different regimens of highly active anti
      retroviral therapy (HAART). They considered patients' levels of cluster of
      differentiation (CD) 4(+) cells and viral load, and they attempted to verify
      whether patients with baseline biochemical signs of bone mineral density loss
      could experience osseointegration impairment. MATERIALS AND METHODS: One of the
      authors, a dentist, placed dental implants in the posterior mandibles of 40
      volunteers, divided into three groups: one composed of HIV-positive patients
      receiving protease inhibitor (PI)-based HAART; a second composed of HIV-positive
      patients receiving nonnucleoside reverse transcriptase inhibitor-based HAART
      (without PI); and a control group composed of HIV-negative participants. The
      authors assessed peri-implant health six and 12 months after implant loading.
      They analyzed the success of the implants in relation to CD4(+) cell counts,
      viral load and baseline pyridinoline and deoxypyridinoline values. RESULTS: The
      authors followed 59 implants for 12 months after loading. Higher baseline levels
      of pyridinoline and deoxypyridinoline found in HIV-positive participants did not
      interfere with osseointegration after 12 months of follow-up. Average peri
      implant bone loss after 12 months was 0.49 millimeters in group 1, 0.47 mm in
      group 2 and 0.55 mm in the control group. CONCLUSIONS: The placement of dental
      implants in HIV-positive patients is a reasonable treatment option, regardless of
      CD4(+) cell count, viral load levels and type of antiretroviral therapy. Longer
      follow-up periods are necessary to ascertain the predictability of the long-term
      success of dental implants in these patients. CLINICAL IMPLICATIONS: Limited
      published scientific evidence is available to guide clinicians in regard to
      possible increased risks associated with dental implant placement in HIV-positive
      patients.

PMID- 21881067
TI  - Inherited epidermolysis bullosa: an update and suggested dental care
      considerations.
AB  - BACKGROUND: Epidermolysis bullosa (EB) is a skin disease characterized by
      epithelial fragility that leads to blistering and erosion of the skin and
      mucosae. The authors conducted a literature review to provide an update on oral
      manifestations and dental care of patients with EB. Literature Search. The
      authors reviewed the dental literature on EB in relation to clinical findings and
      provision of dental care. They searched textbooks and three databases: MEDLINE,
      Cochrane Library and Embase. The authors did not impose any date or publication
      status restrictions. They searched all databases up to August 2010. RESULTS: The
      literature review revealed that four major groups and 32 subtypes of EB can be
      distinguished on the basis of the ultrastructural characteristics of skin
      cleavage, genetic mode of transmission and clinical phenotype. Oral
      manifestations differ in frequency and severity according to the disease subtype,
      but the most common are bullae, which leave painful ulcers on rupture, followed
      by scarring and tissue contraction. Although good oral health status is essential
      to maintaining oral function, dental treatment can induce new lesions and be
      hindered by the sequelae of existing lesions. CLINICAL IMPLICATIONS: Dental
      treatment in patients with EB requires a multidisciplinary approach. Dental
      procedures must be minimally traumatic, and the effectiveness of treatment is
      determined mainly by the patient's general health, cooperation in the dental
      office and at home, oral hygiene and diet.

PMID- 21881068
TI  - A large calcifying lesion of the maxilla in a child.

PMID- 21881069
TI  - Atypical odontalgia: an oral neuropathic pain phenomenon.

PMID- 21881070
TI  - Sealants and dental caries: dentists' perspectives on evidence-based
      recommendations.
AB  - BACKGROUND: The authors conducted a study to survey the perspectives of dentists
      regarding the 2010 American Dental Association (ADA) recommendation to seal non
      cavitated carious lesions (NCCLs) in children and young adults. METHODS: The
      authors mailed a questionnaire to a randomly selected sample of 2,400 general
      dentists (GDs) and pediatric dentists (PDs) in the United States. The sample was
      chosen by the ADA's Survey Center. The questionnaire included two photographs of
      NCCLs (permanent first molar and premolar) in a 12-year-old child. Respondents
      were provided with radiographic findings and asked to choose from several
      management options. RESULTS: In the absence of radiographic evidence of caries,
      37.4 percent and 42.3 percent of GDs and PDs, respectively, indicated that they
      would seal the NCCL in the molar. For the premolar, a significantly lower
      percentage of GDs than of PDs indicated that they would seal the NCCL. With
      radiographic evidence of caries in dentin, less than 4 percent of all dentists
      surveyed indicated that they would seal the NCCLs, and more than 90 percent
      indicated that they would remove the caries and place restorations. Less than 40
      percent of dentists indicated that they sealed NCCLs in their practice.
      CONCLUSIONS: The U.S. dentists surveyed have not adopted evidence-based clinical
      recommendations regarding the sealing of NCCLs. Practice Implications. New
      educational and dissemination programs should be developed regarding these
      evidence-based caries management approaches.

PMID- 21881072
TI  - Temporomandibular disorders affect oral health-related quality of life
      substantially, but limited evidence is available regarding their magnitude of
      impact.

PMID- 21881071
TI  - The effects of mouthpiece use on gas exchange parameters during steady-state
      exercise in college-aged men and women.
AB  - BACKGROUND: The authors conducted a study to assess the effects of custom-fitted
      mouthpieces on gas exchange parameters, including volume of oxygen consumption
      over time [corrected] (VO(2)), volume of oxygen consumption over time per
      kilogram of body weight [corrected] (VO(2) /kg) and volume of carbon dioxide
      production over time [corrected] (VO(2)). METHODS: Sixteen physically fit college
      students aged 18 through 21 years performed two 10-minute treadmill runs (6.5
      miles per hour, 0 percent grade) for each of three treatment conditions
      (mouthpiece, no mouthpiece and nose breathing). The authors assigned the
      conditions randomly for each participant and for each session. They assessed gas
      exchange parameters by using a metabolic measurement system. RESULTS: The authors
      used analysis of variance to compare all variables. They set the significance
      level at alpha = .05 and used a Tukey post hoc analysis of treatment means to
      identify differences between groups. The results showed significant improvements
      (P < .05) in VO(2,) VO(2) /kg and VCO(2) in the mouthpiece condition.
      CONCLUSIONS: The study findings show that use of a custom-fitted mouthpiece
      resulted in improved specific gas exchange parameters. The authors are pursuing
      further studies to explain the mechanisms involved in the improved endurance
      performance exhibited with mouthpiece use. CLINICAL IMPLICATIONS: Dental care
      professionals have an obligation to understand the increasing research evidence
      in support of mouthpiece use during exercise and athletic activity and to educate
      their patients.

PMID- 21881073
TI  - Variations in self-reported provision of services by general dentists in private
      practice.
AB  - BACKGROUND: Variations in dentists' provision of services have been documented,
      but information about contributing factors is limited. METHODS: The authors used
      responses to a 2003 survey of general dentists in private practice in California
      (46 percent response rate; 3,098 dentists included in the final sample) to assess
      variations in service provision and its correlates. They used logistic
      regressions to assess the correlation of various characteristics with the self
      reported percentage of time spent providing services. RESULTS: The results show
      variations in services provided by general dentists in private practice. Multiple
      factors, including the dentist's sex, region of practice, employment of
      hygienists, patients' race and population income in the area of practice were
      significantly and independently associated with provision of services.
      CONCLUSIONS: The survey results reflect practice variations that existed before
      the latest economic downturn, which resulted in a loss of jobs and medical and
      dental insurance. The data serve as the baseline for future studies of changes in
      dental practice and for assessing the impact of the 2010 health care reform
      legislation on dental practice. Practice Implications. Improvements in oral
      health care, the recent economic decline and health care reform may lead to
      changes in dental practice and in the dental workforce.

PMID- 21881076
TI  - Dentists and marketing.

PMID- 21881077
TI  - Are dentists losing their status as 'professionals'?

PMID- 21881078
TI  - Dental radiographs: benefits and safety.

PMID- 21881080
TI  - Distinct pharmacologic substrate in lidocaine-sensitive, repetitive atrial
      tachycardia.
AB  - Lidocaine-sensitive, repetitive atrial tachycardia is an uncommon arrhythmia. The
      electrophysiologic substrate is still unknown, and the pharmacologic responses
      have not been fully explored. The aim of this study was to investigate the
      effects of intravenous adenosine and verapamil in patients with lidocaine
      sensitive atrial tachycardia. In 9 patients with repetitive uniform atrial
      tachycardia, the response to intravenous adenosine (12 mg), lidocaine (1 mg/kg
      body weight), and verapamil (10 mg) were sequentially investigated. Simultaneous
      12-lead electrocardiogram (ECG) was recorded at baseline and continuously
      monitored thereafter. Tracings were obtained at regularly timed intervals right
      after the administration of each drug to evaluate changes in the arrhythmia
      characteristics. Repetitive atrial tachycardia was abolished by intravenous
      lidocaine in the 9 patients within the first 2 minutes after the end of
      injection. Adenosine suppressed the arrhythmia in 2 patients and shortened the
      runs of atrial ectopic activity in 1 patient, while verapamil was effective in 2
      patients, 1 of them insensitive to adenosine and the other 1 sensitive to this
      agent. In 5 patients, the arrhythmia was abolished by radiofrequency ablation at
      different sites of the right atrium. Lidocaine-sensitive atrial tachycardia may
      eventually be also suppressed by adenosine and/or verapamil. This suggests that
      this enigmatic arrhythmia may be caused by different underlying
      electrophysiologic substrates and that at least in some cases, delayed
      afterdepolarizations seem to play a determining role.

PMID- 21881081
TI  - Art, science and randomization.

PMID- 21881079
TI  - Formative research on HPV vaccine acceptability among Latina farmworkers.
AB  - The purpose of this study was to identify the barriers and benefits to human
      papillomavirus (HPV) vaccination in a low-income, Latina farmworker population in
      central Florida. This study reports on formative qualitative research conducted
      on perceptions of benefits, barriers, costs, place, and promotion related to the
      HPV vaccine from surveys and interviews with a sample of 46 low-income, Latina
      farm workers and 19 health care workers serving this population. It was found
      that Latina farmworkers hold many misperceptions about the HPV vaccine and the
      potential links between HPV infection and cervical cancer. In addition, it was
      observed that HPV vaccination intention was inversely related to concerns about
      adolescent sexual behavior and low perceived risk of infection but might be
      positively influenced by belief in illness prevention and physician
      recommendation. These findings add to the growing research on HPV vaccine
      acceptability among Latina subgroups to inform intervention development,
      marketing materials, education, and policy.

PMID- 21881082
TI  - Diverging health policy and mortality.

PMID- 21881084
TI  - The first description of hayfever?

PMID- 21881085
TI  - Why the ex-colonial medical brain drain?

PMID- 21881086
TI  - John Marshall's first description of surgical electrocautery.

PMID- 21881087
TI  - The breast screening programme and misinforming the public.
AB  - The information provided to the public by the NHS Breast Screening Programme has
      been criticized for lack of balance, omission of information on harms and
      substantially exaggerated estimates of benefit. These shortcomings have been
      particularly evident in the various invitation leaflets for breast screening and
      in the Programme's own 2008 Annual Review, which celebrated 20 years of
      screening. The debate on screening has been heated after new data published in
      the last two years questioned the benefit and documented substantial harm. We
      therefore analysed whether the recent debate and new pivotal data about breast
      screening has had any impact on the contents of the new 2010 leaflet and on the
      2010 Annual Review. We conclude that spokespeople for the Programme have stuck to
      the beliefs about benefit that prevailed 25 years ago. Concerns about over
      diagnosis have not been addressed either and official documents still downplay
      this most important harm of breast cancer screening.

PMID- 21881089
TI  - Acute unilateral facial and orbital pain: an unusual presentation of superior
      vena cava obstruction.

PMID- 21881088
TI  - Measuring NHS performance 1990-2009 using amenable mortality: interpret with
      care.
AB  - OBJECTIVES: The new performance framework for the NHS in England will assess how
      well health services are preventing people from dying prematurely, based on the
      concept of mortality amenable to healthcare. We ask how the different parts of
      the UK would be assessed had this measure been in use over the past two decades,
      a period that began with somewhat lower levels of health expenditure in England
      and Wales than in Scotland and Northern Ireland but which, after 1999, saw the
      gap closing. DESIGN: We assessed the change in age-standardized death rates in
      England and Wales, Northern Ireland and Scotland in two time periods: 1990-1999
      and 1999-2009. Mortality data by five-year age group, sex and cause of death for
      the years 1990 to 2009 were analysed using age-standardized death rates from
      causes considered amenable to healthcare. The absolute change was assessed by
      fitting linear regression and the relative change was estimated as the average
      annual percent decline for the two periods. SETTING: United Kingdom.
      PARTICIPANTS: Not applicable. MAIN OUTCOME MEASURES: Mortality from causes
      amenable to healthcare. RESULTS: Between 1990 and 1999 deaths amenable to medical
      care had been falling more slowly in England and Wales than in Scotland and
      Northern Ireland. However the rate of decline in England and Wales increased
      after 1999 when funding of the NHS there increased. Examination of individual
      causes of death reveals a complex picture, with some improvements, such as in
      breast cancer deaths, occurring simultaneously across the UK, reflecting changes
      in diagnosis and treatment that took place in each nation at the same time, while
      others varied. CONCLUSIONS: Amenable mortality is a useful indicator of health
      system performance but there are many methodological issues that must be taken
      into account when interpreting it once it is adopted for routine use in England.

PMID- 21881090
TI  - Why the 1948 MRC trial of streptomycin used treatment allocation based on random
      numbers.

PMID- 21881091
TI  - Nobel Prizes in medicine: are clinicians out of fashion?

PMID- 21881093
TI  - Differential outcome of schizophrenia: where we are and where we would like to
      be.
AB  - Studies examining comparative outcomes of schizophrenia in high-income countries
      with those in low- and middle-income countries remain of interest to researchers
      and may be of value in understanding some environmental factors that influence
      the course and outcome of the disorder. The view that the disorder has a better
      outcome in low- and middle-income countries compared with high-income countries,
      even though widespread and supported by a set of World Health Organization (WHO)
      studies, requires further testing and exploration. Unfortunately, although not
      insurmountable, the obstacles for such studies both in terms of implementation
      and interpretation are considerable.

PMID- 21881094
TI  - Alcohol-related brain damage: a 21st-century management conundrum.
AB  - Alcohol-related brain damage has a growing impact on service provision. Despite
      the benefit of therapeutic interventions and a relatively good prognosis in the
      context of service provision, few services exist. Both national and local
      initiatives are required in order to provide psychosocial rehabilitation for this
      marginalised group of patients.

PMID- 21881095
TI  - Combining routine outcomes measurement and 'Payment by Results': will it work and
      is it worth it?
AB  - The Department of Health in England has long encouraged the routine measurement
      of clinical outcomes in mental health services but has now decided to use outcome
      measures as part of a new payments system - Payment by Results. We examine how
      these two policies should or might interact.

PMID- 21881096
TI  - Abortion and mental health: quantitative synthesis and analysis of research
      published 1995-2009.
AB  - BACKGROUND: Given the methodological limitations of recently published
      qualitative reviews of abortion and mental health, a quantitative synthesis was
      deemed necessary to represent more accurately the published literature and to
      provide clarity to clinicians. AIMS: To measure the association between abortion
      and indicators of adverse mental health, with subgroup effects calculated based
      on comparison groups (no abortion, unintended pregnancy delivered, pregnancy
      delivered) and particular outcomes. A secondary objective was to calculate
      population-attributable risk (PAR) statistics for each outcome. METHOD: After the
      application of methodologically based selection criteria and extraction rules to
      minimise bias, the sample comprised 22 studies, 36 measures of effect and 877 181
      participants (163 831 experienced an abortion). Random effects pooled odds ratios
      were computed using adjusted odds ratios from the original studies and PAR
      statistics were derived from the pooled odds ratios. RESULTS: Women who had
      undergone an abortion experienced an 81% increased risk of mental health
      problems, and nearly 10% of the incidence of mental health problems was shown to
      be attributable to abortion. The strongest subgroup estimates of increased risk
      occurred when abortion was compared with term pregnancy and when the outcomes
      pertained to substance use and suicidal behaviour. CONCLUSIONS: This review
      offers the largest quantitative estimate of mental health risks associated with
      abortion available in the world literature. Calling into question the conclusions
      from traditional reviews, the results revealed a moderate to highly increased
      risk of mental health problems after abortion. Consistent with the tenets of
      evidence-based medicine, this information should inform the delivery of abortion
      services.

PMID- 21881097
TI  - Advanced dental disease in people with severe mental illness: systematic review
      and meta-analysis.
AB  - BACKGROUND: Psychiatric patients have increased comorbid physical illness. There
      is less information concerning dental disease in this population in spite of risk
      factors including diet and psychotropic side-effects (such as xerostomia). Aims
      To compare the oral health of people with severe mental illness with that of the
      general population. METHOD: A systematic search for studies from the past 20
      years was conducted using Medline, PsycINFO, Embase and article bibliographies.
      Papers were independently assessed. The primary outcome was total tooth loss
      (edentulousness), the end-stage of both untreated caries and periodontal disease.
      We also assessed dental decay through standardised measures: the mean number of
      decayed, missing and filled teeth (DMFT) or surfaces (DMFS). For studies lacking
      a control group we used controls of similar ages from a community survey within
      10 years of the study. RESULTS: We identified 21 papers of which 14 had
      sufficient data (n = 2784 psychiatric patients) and suitable controls (n = 31
      084) for a random effects meta-analysis. People with severe mental illness had
      3.4 times the odds of having lost all their teeth than the general community (95%
      CI 1.6-7.2). They also had significantly higher scores for DMFT (mean difference
      6.2, 95% CI 0.6-11.8) and DMFS (mean difference 14.6, 95% CI 4.1-25.1).
      Fluoridated water reduced the gap in oral health between psychiatric patients and
      the general population. CONCLUSIONS: Psychiatric patients have not shared in the
      improving oral health of the general population. Management should include oral
      health assessment using standard checklists that can be completed by non-dental
      personnel. Interventions include oral hygiene and management of xerostomia.

PMID- 21881098
TI  - Cross-national clinical and functional remission rates: Worldwide Schizophrenia
      Outpatient Health Outcomes (W-SOHO) study.
AB  - BACKGROUND: Evidence suggests that schizophrenia may have a better outcome for
      individuals living in low- and middle-income countries compared with affluent
      settings. AIMS: To determine the frequency of symptom and functional remission in
      out-patients with schizophrenia in different regions of the world. METHOD: Using
      data from the Worldwide-Schizophrenia Outpatient Health Outcomes (W-SOHO) study
      we measured clinical and functional remission in out-patients with schizophrenia
      in different regions of the world, and examined sociodemographic and clinical
      factors associated with these outcomes. The 11 078 participants analysed from 37
      participating countries were grouped into 6 regions: South Europe, North Europe,
      Central and Eastern Europe, Latin America, North Africa and Middle East, and East
      Asia. RESULTS: In total, 66.1% achieved clinical remission during the 3-year
      follow-up (range: 60.1% in North Europe to 84.4% in East Asia) and 25.4% achieved
      functional remission (range: 17.8% in North Africa and Middle East to 35.0% in
      North Europe). Regional differences were not explained by participants' clinical
      characteristics. Baseline social functioning, being female and previously
      untreated were consistent predictors of remission across regions. CONCLUSIONS:
      Clinical outcomes of schizophrenia seem to be worse in Europe compared with other
      regions. However, functional remission follows a different pattern.

PMID- 21881099
TI  - Schizophrenia with the 22q11.2 deletion and additional genetic defects: case
      history.
AB  - The 22q11.2 deletion is the most prominent known genetic risk factor for
      schizophrenia, but its penetrance is at most approximately 50% suggesting that
      additional risk factors are required for disease progression. We examined a woman
      with schizophrenia with this deletion for such risk factors. She had high plasma
      pentosidine levels ('carbonyl stress') and a frameshift mutation in the
      responsible gene, GLO1. She also had a constant exotropia, so we examined the
      PHOX2B gene associated with both schizophrenia and strabismus, and detected a 5
      alanine deletion. We propose that the combination of these genetic defects may
      have exceeded the threshold for the manifestation of schizophrenia.

PMID- 21881100
TI  - Mitral valve prolapse and anxiety disorders.
AB  - We investigated whether there is an association between anxiety disorders and
      mitral valve prolapse. We compared mitral valve prolapse prevalence in
      individuals with panic disorder (n = 41), social anxiety disorder (n = 89) and in
      healthy controls (n = 102) in an attempt to overcome the biases of previous
      studies. Our results show no associations between panic disorder or social
      anxiety disorder and mitral valve prolapse, regardless of the diagnostic criteria
      employed, and that the relationship between these conditions seems not to be
      clinically relevant.

PMID- 21881101
TI  - Need to identify modifiable risk factors of dementia in the older UK African
      Caribbean population.

PMID- 21881102
TI  - How to interpret different results for CRHTT data.

PMID- 21881103
TI  - Internet-based CBT for severe health anxiety.

PMID- 21881104
TI  - Childhood psychotic symptoms: link between non-consensual sex and later
      psychosis.

PMID- 21881105
TI  - Revascularisation in patients with mental illness.

PMID- 21881106
TI  - Generalised spike-and-slow-wave complexes without seizures in schizophrenia.

PMID- 21881111
TI  - Is there still hope after prions have spread within the brain?

PMID- 21881113
TI  - Respiratory syncytial virus load, viral dynamics, and disease severity in
      previously healthy naturally infected children.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) disease severity was thought to be
      a result of host immunopathology but alternatively may be driven by high-level
      viral replication. The relationships between RSV load, viral clearance dynamics,
      and disease severity have not been carefully evaluated. METHODS: Previously
      healthy RSV-infected children <2 years old were recruited. RSV load was measured
      in respiratory secretions by fresh quantitative culture over 3 hospital days.
      Measures of disease severity were hospital admission, duration of
      hospitalization, requirement for intensive care, and respiratory failure.
      RESULTS: Multivariate logistic regression models revealed independent predictors
      of increased duration of hospitalization: male sex, lower weight, and higher
      viral load on any day. Viral loads at day 3 were more significantly associated
      with requirement for intensive care and respiratory failure than were viral loads
      at earlier time points. Faster RSV clearance was independently associated with
      shorter hospitalization. DISCUSSION: These observations challenge the
      immunopathology-based pathogenesis paradigm. They also have major therapeutic
      implications, suggesting that application of antiviral agents early in the
      disease course, even at a time when viral replication is at its highest, might
      improve subsequent morbidity by significantly lowering viral load and direct
      viral cytopathic effects, and aborting the potential downstream immunopathology.

PMID- 21881112
TI  - Viruslike particle vaccine induces protection against respiratory syncytial virus
      infection in mice.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) is the leading cause of
      bronchiolitis and viral death in infants. Despite decades of research with
      traditional or subunit vaccine approaches, there are no approved RSV vaccines.
      New approaches are therefore urgently needed to develop effective RSV vaccines.
      METHODS: We developed viruslike particles (VLPs) consisting of an influenza virus
      matrix (M1) protein core and RSV-F or -G on the surface. We tested the
      immunogenicity and vaccine efficacy of these VLPs (RSV-F, RSV-G) in a mouse
      model. RESULTS: Intramuscular vaccination with RSV-F or RSV-G VLPs elicited IgG2a
      dominant RSV-specific immunoglobulin G (IgG) antibody responses against RSV-A2
      viruses in both serum and lung extract. Mice immunized with VLPs (RSV-F or RSV-G)
      showed higher viral neutralizing antibodies in vitro and significantly decreased
      lung virus loads in vivo after live RSV-A2 challenge. RSV-G VLPs showed better
      protective efficacy than RSV-F VLPs as determined by the levels of lung virus
      loads and morbidity postchallenge. CONCLUSIONS: This study demonstrates that VLP
      vaccination provides effective protection against RSV infection. VLPs containing
      RSV-F and/or RSV-G are potential vaccine candidates against RSV.

PMID- 21881114
TI  - Mixed infection and strain diversity in congenital cytomegalovirus infection.
AB  - BACKGROUND: Cytomegalovirus (CMV), the most common cause of congenital infection,
      exhibits extensive genetic variability. We sought to determine whether multiple
      CMV strains can be transmitted to the fetus and to describe the distribution of
      genotypes in the saliva, urine, and blood. METHODS: Study subjects consisted of a
      convenience sampling of 28 infants found to be CMV-positive on newborn screening
      as part of an ongoing study. Genotyping was performed on saliva specimens
      obtained during newborn screening and urine, saliva, and blood obtained at a
      later time point within the first 3 weeks of life. RESULTS: Six (21.4%) of the 28
      saliva samples obtained within the first 2 days of life contained >1 CMV
      genotype. Multiple CMV genotypes were found in 39% (5/13) of urine, saliva, and
      blood samples obtained within the first 3 weeks of life from 13 of the 28
      newborns. There was no predominance of a CMV genotype at a specific site;
      however, 4 infants demonstrated distinct CMV strains in different compartments.
      CONCLUSIONS: Infection with multiple CMV strains occurs in infants with
      congenital CMV infection. The impact of intrauterine infection with multiple
      virus strains on the pathogenesis and long-term outcome remains to be elucidated.

PMID- 21881115
TI  - The 2009 pandemic H1N1 D222G hemagglutinin mutation alters receptor specificity
      and increases virulence in mice but not in ferrets.
AB  - BACKGROUND: The D222G (H1 numbering) hemagglutinin (HA) mutation within the
      receptor-binding site was detected with higher frequencies in severe cases of
      2009 pandemic H1N1 (pH1N1) infections. We investigated the impact of this
      mutation in vitro and in animal models using recombinant pH1N1 viruses. METHODS:
      The recombinant D222G HA mutant was generated from a wild-type (WT) clinical
      strain by using reverse genetics and site-directed mutagenesis. Replicative
      capacities were determined in MDCK and MDCK-alpha2,6 cells. Antigenicity was
      characterized by HA inhibition and microneutralization assays. HA titers were
      determined using human, chicken, and resialylated turkey red blood cells (RBCs).
      Virulence and contact-transmissibility were analyzed in mice and ferrets.
      RESULTS: The recombinant D222G virus grew to significantly higher titers and
      generated larger viral plaques compared with the WT in MDCK but not in MDCK
      alpha2,6 cells. The mutant also showed a significant reduction in HA titers using
      alpha2,6-expressing RBCs. The 2 recombinants were antigenically similar. The
      D222G mutant virus induced higher lung viral titers and alveolar inflammation in
      mice whereas the 2 recombinants had similar impacts in ferrets. CONCLUSIONS: The
      D222G HA mutation alters receptor binding specificity, resulting in higher lung
      titers in mice. This could contribute to the higher case fatality rates reported
      in humans.

PMID- 21881116
TI  - Enhanced replication of hepatitis B virus with frameshift in the precore region
      found in fulminant hepatitis patients.
AB  - BACKGROUND: The genotype B of hepatitis B virus (HBV) was reported to associate
      with fulminant hepatitis (FH). We aimed to clarify the characteristics of HBV
      obtained from FH patients in an area of Japan where genotype B HBV is prevalent.
      METHODS: Using serum samples of 16 HBV-associated FH patients, partial HBV
      sequences were determined. The effects of HBV mutation/insertion/deletion were
      evaluated using an in vitro HBV replication system. RESULTS: Of the 16 HBV
      isolates, 31% belonged to subgenotype B1/Bj, 38% were subgenotype B2/Ba, and 31%
      were subgenotype C2/Ce. Notably, the single nucleotide insertion/deletion that
      resulted in a frameshift of the precore protein was found exclusively in 60% of
      B1/Bj strains. An in vitro study showed that all of the frameshift mutants had
      significantly higher amounts of HBV DNA than did the wild type. One of the
      isolates had a novel insertion of A between nucleotides 1900 and 1901, which
      resulted in a 3-nucleotide change within the Kozak sequence of the core protein
      and enhanced the core protein expression in vitro. CONCLUSIONS: The frameshift
      insertion/deletion in the precore region enhanced HBV replication and might be
      associated with the development of FH by the subgenotype B1/Bj HBV.

PMID- 21881117
TI  - Protection from arthritis and myositis in a mouse model of acute chikungunya
      virus disease by bindarit, an inhibitor of monocyte chemotactic protein-1
      synthesis.
AB  - Chikungunya virus (CHIKV) is associated with outbreaks of infectious rheumatic
      disease in humans. Using a mouse model of CHIKV arthritis and myositis, we show
      that tumor necrosis factor-alpha, interferon-gamma, and monocyte chemotactic
      protein 1 (MCP-1) were dramatically induced in tissues from infected mice. The
      same factors were detected in the serum of patients with CHIKV-induced
      polyarthralgia and polyarthritis, with MCP-1 levels being particularly elevated.
      Bindarit (MCP inhibitor) treatment ameliorated CHIKV disease in mice.
      Histological analysis of muscle and joint tissues showed a reduction in
      inflammatory infiltrate in infected mice treated with bindarit. These results
      suggest that bindarit may be useful in treating CHIKV-induced arthritides in
      humans.

PMID- 21881119
TI  - Stem cell therapy extends incubation and survival time in prion-infected mice in
      a time window-dependant manner.
AB  - Prion diseases, which are mostly represented in humans by Creutzfeldt-Jakob
      disease, are transmissible neurodegenerative disorders characterized by
      vacuolization and neuronal loss, as well as by the accumulation of an abnormal
      form of the prion protein. These disorders have yet no effective treatment, and
      drugs that block prion replication in vitro do not significantly slow down the
      progression of the disease when used in vivo at late stages. Cell therapy that
      has been already tested in other neurodegenerative disorders therefore represents
      an interesting alternative approach. In this study, we showed for the first time
      in prion diseases that intracerebral transplantation of fetal neural stem cells
      significantly extended both incubation and survival time. This result was
      dependant on the time window chosen for the engraftment and was obtained with
      both genetically modified and wild-type stem cells, therefore forging a path
      toward efficient stem cell therapy for human prion diseases.

PMID- 21881118
TI  - Genetic variants and susceptibility to neurological complications following West
      Nile virus infection.
AB  - To determine genetic factors predisposing to neurological complications following
      West Nile virus infection, we analyzed a cohort of 560 neuroinvasive case
      patients and 950 control patients for 13 371 mostly nonsynonymous single
      nucleotide polymorphisms (SNPs). The top 3 SNPs on the basis of statistical
      significance were also in genes of biological plausibility: rs2066786 in RFC1
      (replication factor C1) (P = 1.88 * 10(-5); odds ratio [OR], 0.68 [95% confidence
      interval {CI}, .56-.81]); rs2298771 in SCN1A (sodium channel, neuronal type I
      alpha subunit) (P = 5.87 * 10(-5); OR, 1.47 [95% CI, 1.21-1.77]); and rs25651 in
      ANPEP (ananyl aminopeptidase) (P = 1.44 * 10(-4); OR, 0.69 [95% CI, .56-.83]).
      Additional genotyping of these SNPs in a separate sample of 264 case patients and
      296 control patients resulted in a lack of significance in the replication
      cohort; joint significance was as follows: rs2066786, P = .0022; rs2298771, P =
      .005; rs25651, P = .042. Using mostly nonsynonymous variants, we therefore did
      not identify genetic variants associated with neuroinvasive disease.

PMID- 21881120
TI  - Changes in serogroup and genotype prevalence among carried meningococci in the
      United Kingdom during vaccine implementation.
AB  - BACKGROUND: Herd immunity is important in the effectiveness of conjugate
      polysaccharide vaccines against encapsulated bacteria. A large multicenter study
      investigated the effect of meningococcal serogroup C conjugate vaccine
      introduction on the meningococcal population. METHODS: Carried meningococci in
      individuals aged 15-19 years attending education establishments were investigated
      before and for 2 years after vaccine introduction. Isolates were characterized by
      multilocus sequence typing, serogroup, and capsular region genotype and changes
      in phenotypes and genotypes assessed. RESULTS: A total of 8462 meningococci were
      isolated from 47 765 participants (17.7%). Serogroup prevalence was similar over
      the 3 years, except for decreases of 80% for serogroup C and 40% for serogroup
      29E. Clonal complexes were associated with particular serogroups and their
      relative proportions fluctuated, with 12 statistically significant changes (6 up,
      6 down). The reduction of ST-11 complex serogroup C meningococci was probably due
      to vaccine introduction. Reasons for a decrease in serogroup 29E ST-254
      meningococci (from 1.8% to 0.7%) and an increase in serogroup B ST-213 complex
      meningococci (from 6.7% to 10.6%) were less clear. CONCLUSIONS: Natural
      fluctuations in carried meningococcal genotypes and phenotypes a can be affected
      by the use of conjugate vaccines, and not all of these changes are anticipatable
      in advance of vaccine introduction.

PMID- 21881121
TI  - Outbreaks of mycobacterium tuberculosis MDR strains induce high IL-17 T-cell
      response in patients with MDR tuberculosis that is closely associated with high
      antigen load.
AB  - BACKGROUND: The proinflammatory cytokine interleukin 17 (IL-17) plays an
      important role in immune responses but it is also associated with tissue-damaging
      inflammation. So, we evaluated the ability of Mycobacterium tuberculosis clinical
      isolates to induce IL-17 in tuberculosis (TB) patients and in healthy human
      tuberculin reactors (PPD(+)HD). METHODS: IL-17, interferon gamma (IFN-gamma), and
      interleukin 23 (IL-23) receptor expression were evaluated ex vivo and cultured
      peripheral blood mononuclear cells from TB and PPD(+)HD stimulated with
      irradiated clinical isolates from multidrug resistant (MDR) outbreaks M (Haarlem
      family) and Ra (Latin American-Mediterranean family), as well as drug-susceptible
      isolates belonging to the same families and laboratory strain H37Rv for 48 hours
      in T-cell subsets by flow cytometry. RESULTS: We observed that: (1) MDR strains M
      and Ra are stronger IL-17 inducers than drug-susceptible Mtb strains of the
      Haarlem and Latin American-Mediterranean families, (2) MDR-TB patients show the
      highest IL-17 expression that is independent on the strain, (3) IL-17 expression
      is dependent on CD4(+) and CD8(+) T cells associates with persistently high
      antigen load. CONCLUSIONS: IL-17--producing T cells could play an
      immunopathological role in MDR-TB promoting severe tissue damage, which may be
      associated with the low effectiveness of the second-line drugs employed in the
      treatment.

PMID- 21881122
TI  - Haemophilus influenzae protein E binds to the extracellular matrix by
      concurrently interacting with laminin and vitronectin.
AB  - Nontypeable Haemophilus influenzae (NTHi) causes otitis media and is commonly
      found in patients with chronic obstructive pulmonary disease (COPD). Adhesins are
      important for bacterial attachment and colonization. Protein E (PE) is a recently
      characterized ubiquitous 16 kDa adhesin with vitronectin-binding capacity that
      results in increased survival in serum. In addition to PE, NTHi utilizes
      Haemophilus adhesion protein (Hap) that binds to the basement-membrane
      glycoprotein laminin. We show that most clinical isolates bind laminin and that
      both Hap and PE are crucial for the NTHi-dependent interaction with laminin as
      revealed with different mutants. The laminin-binding region is located at the N
      terminus of PE, and PE binds to the heparin-binding C-terminal globular domain of
      laminin. PE simultaneously attracts vitronectin and laminin at separate binding
      sites, proving the multifunctional nature of the adhesin. This previously unknown
      PE-dependent interaction with laminin may contribute to NTHi colonization,
      particularly in smokers with COPD.

PMID- 21881123
TI  - BCG vaccination induces different cytokine profiles following infant BCG
      vaccination in the UK and Malawi.
AB  - BACKGROUND: BCG vaccination of infants is thought to provide good protection in
      all settings. This study investigated whether Malawian infants made weaker
      responses across a cytokine panel after BCG vaccination, compared with UK
      infants. METHODS: Diluted whole-blood samples were cultured with Mycobacterium
      tuberculosis purified protein derivative for 6 days from BCG-vaccinated infants 3
      months (n = 40 Malawi, 28 UK) and 12 months (n = 34 Malawi, 26 UK) after
      vaccination, and also from UK unvaccinated infants (n = 9 at 3 months, n = 10 at
      12 months). Forty-two cytokines were measured in supernatants using a multiplex
      bead array assay. Principal component analysis was used to summarize the overall
      patterns in cytokine responses. RESULTS: We found differences in median responses
      in 27 of the 42 cytokines: 7 higher in the UK and 20 higher in Malawi. The
      cytokines with higher responses in the UK were all T helper 1 related. The
      cytokines with higher responses in Malawi included innate proinflammatory
      cytokines, regulatory cytokines, interleukin 17, T helper 2 cytokines,
      chemokines, and growth factors. Principal component analysis separated the BCG
      vaccinated infants from Malawi from the UK vaccinated infants and from the
      unvaccinated infants. CONCLUSIONS: Malawian infants make cytokine responses
      following BCG vaccination, but the cytokine profile is different from that in the
      UK. The different biosignatures following BCG vaccination in the 2 settings may
      indicate variability in the protective efficacy of infant BCG vaccination.

PMID- 21881124
TI  - Lowering the threshold of lung innate immune cell activation alters
      susceptibility to secondary bacterial superinfection.
AB  - BACKGROUND: Previous studies have shown that the interaction of CD200R, a myeloid
      inhibitory receptor, with its ligand, CD200, is critical in the control of innate
      immune activation in the lung. METHODS AND RESULTS: Using a mouse model of
      bacterial superinfection following influenza, we show that an absence of CD200R
      (a negative regulator highly expressed by macrophages and dendritic cells),
      restricts commensal and exogenous bacterial invasiveness and completely prevents
      the mortality observed in wild-type mice. This benefit is due to a heightened
      innate immune response to influenza virus in cd200r knockout mice that limits
      immune pathogenesis and viral load. In wild-type mice, apoptotic cells expressing
      CD200 that we believe contribute to the suppressed innate immune response to
      bacteria dominate during the resolution phase of influenza-induced inflammation.
      We also show for the first time the presence of a variety of previously
      unidentified bacterial species in the lower airways that are significantly
      adjusted by influenza virus infection and may contribute to the pathophysiology
      of disease. CONCLUSIONS: The interaction of CD200 with CD200R therefore
      contributes to the hyporesponsive innate immune state following influenza virus
      infection that predisposes to secondary bacterial infection, a phenomenon that
      has the potential for immune modulation.

PMID- 21881125
TI  - The role of migration and domestic transmission in the spread of HIV-1 non-B
      subtypes in Switzerland.
AB  - BACKGROUND: By analyzing human immunodeficiency virus type 1 (HIV-1) pol
      sequences from the Swiss HIV Cohort Study (SHCS), we explored whether the
      prevalence of non-B subtypes reflects domestic transmission or migration
      patterns. METHODS: Swiss non-B sequences and sequences collected abroad were
      pooled to construct maximum likelihood trees, which were analyzed for Swiss
      specific subepidemics, (subtrees including >=80% Swiss sequences, bootstrap >70%;
      macroscale analysis) or evidence for domestic transmission (sequence pairs with
      genetic distance <1.5%, bootstrap >=98%; microscale analysis). RESULTS: Of 8287
      SHCS participants, 1732 (21%) were infected with non-B subtypes, of which A (n =
      328), C (n = 272), CRF01_AE (n = 258), and CRF02_AG (n = 285) were studied
      further. The macroscale analysis revealed that 21% (A), 16% (C), 24% (CRF01_AE),
      and 28% (CRF02_AG) belonged to Swiss-specific subepidemics. The microscale
      analysis identified 26 possible transmission pairs: 3 (12%) including only
      homosexual Swiss men of white ethnicity; 3 (12%) including homosexual white men
      from Switzerland and partners from foreign countries; and 10 (38%) involving
      heterosexual white Swiss men and females of different nationality and
      predominantly nonwhite ethnicity. CONCLUSIONS: Of all non-B infections diagnosed
      in Switzerland, <25% could be prevented by domestic interventions. Awareness
      should be raised among immigrants and Swiss individuals with partners from high
      prevalence countries to contain the spread of non-B subtypes.

PMID- 21881126
TI  - Induction of innate immune responses by SIV in vivo and in vitro: differential
      expression and function of RIG-I and MDA5.
AB  - Interferon-beta induction occurs during acute simian immunodeficiency virus (SIV)
      infection in the brain. We have examined expression and function of cytosolic RNA
      sensors, retinoic acid inducible gene I (RIG-I), and melanoma differentiation
      associated protein 5 (MDA5), in vivo in the brain of our consistent, accelerated
      SIV-macaque model and in vitro in SIV-infected macaque macrophages to identify
      the pathway of type I interferon (IFN) induction. MDA5 messenger RNA (mRNA) and
      protein were expressed at higher levels in the brain than RIG-I, with protein
      expression correlating with the severity of disease from 42 until 84 days post
      inoculation. The siRNA experiments reveal that mRNA expression of IFN-inducible
      gene MxA is dependent on MDA5, but not RIG-I. Finally, we demonstrate that SIV
      infection leads to the production of double-stranded RNA in vivo, which may act
      as the MDA5 ligand. We have shown for the first time to our knowledge the
      functional role of MDA5 in the innate immune response to SIV infection.

PMID- 21881127
TI  - Transmission clustering drives the onward spread of the HIV epidemic among men
      who have sex with men in Quebec.
AB  - Phylodynamic analysis and epidemiologic data identified 3 patterns of spread of
      primary human immunodeficiency virus type 1 infection (PHI) among men who have
      sex with men (2001-2009): 420 unique PHIs, 102 small clusters (2-4 PHIs per
      cluster, n = 280), and 46 large clusters (5-31 PHIs per cluster, n = 450). Large
      clusters disproportionately increased from 25.2% of PHIs in 2005 to 39.1% in 2009
      (chi(2) = 33.9, P < .001). Scalar expansion of large clusters over 11 months
      (interquartile range, 3.5-25.5 months) correlated with cluster membership size
      (r(2) = 0.174, F = 4.424, P = .047). PHI cohort data revealed variations in
      social networks and risk behaviors among the 3 groups, suggesting the need for
      tailored prevention measures.

PMID- 21881128
TI  - Prolonged selection of pfmdr1 polymorphisms after treatment of falciparum malaria
      with artemether-lumefantrine in Uganda.
AB  - We compared the prevalence of key pfmdr1 alleles between pretreatment Plasmodium
      falciparum parasite isolates and parasites that emerged after treatment of
      uncomplicated malaria in a longitudinal cohort of Ugandan children. The pfmdr1
      86N, 184F, and 1246D alleles were selected after treatment with artemether
      lumefantrine, but not after artesunate-amodiaquine or amodiaquine-sulfadoxine
      pyrimethamine. Remarkably, selection persisted in infections presenting up to
      about 60 days after treatment with artemether-lumefantrine. Thus, parasites
      selected for decreased drug sensitivity can appear long after predicted exposure
      to antimalarial drugs. Continued surveillance of the clinical efficacy and in
      vitro activity of new combination therapies is warranted.

PMID- 21881129
TI  - The NTS-DBL2X region of VAR2CSA induces cross-reactive antibodies that inhibit
      adhesion of several Plasmodium falciparum isolates to chondroitin sulfate A.
AB  - BACKGROUND: Binding to chondroitin sulfate A by VAR2CSA, a parasite protein
      expressed on infected erythrocytes, allows placental sequestration of Plasmodium
      falciparum-infected erythrocytes. This leads to severe consequences such as
      maternal anemia, stillbirths, and intrauterine growth retardation. The latter has
      been clearly associated to increased morbidity and mortality of the infants.
      Acquired anti-VAR2CSA antibodies have been associated with improved pregnancy
      outcomes, suggesting a vaccine could prevent the syndrome. However, identifying
      functionally important regions in the large VAR2CSA protein is difficult.
      METHODS: Using genetic immunization, we raised polyclonal antisera against
      overlapping segments of VAR2CSA in mice and rabbits. The adhesion-inhibition
      capacities of induced antisera and of specific antibodies purified from plasma of
      malaria-exposed pregnant women were assessed on laboratory-adapted parasite lines
      and field isolates expressing VAR2CSA. Competition enzyme-linked immunosorbent
      assay (ELISA) was employed to analyze functional resemblance between antibodies
      induced in animals and those naturally acquired by immune multigravidae. RESULTS:
      Antibodies targeting the N-terminal sequence (NTS) up to DBL2X (NTS-DBL2X)
      efficiently blocked parasite adhesion to chondroitin sulfate A in a manner
      similar to that of antibodies raised against the entire VAR2CSA extracellular
      domain. Interestingly, naturally acquired antibodies and those induced by
      vaccination against NTS-DBL2X target overlapping strain-transcendent anti
      adhesion epitopes. CONCLUSIONS: This study highlights an important step achieved
      toward development of a protective vaccine against placental malaria.

PMID- 21881130
TI  - IL-10 neutralization promotes parasite clearance in splenic aspirate cells from
      patients with visceral leishmaniasis.
AB  - The mechanisms underlying the failure to contain the growth of Leishmania
      parasites in human visceral leishmaniasis (VL) are not understood. L donovani
      amastigotes were quantified in cultured splenic aspirate cells to assess the
      function of IL-10 in lesional tissue ex vivo. In 67 patients with active VL, IL
      10 neutralization promoted parasite killing in 73% and complete clearance in 30%,
      while 18% had more parasites and 9% did not change. The splenic cells secreted
      increased levels of both tumor necrosis factor alpha (TNFalpha) and interferon
      gamma (IFNgamma) under IL-10-neutralizing conditions. These findings provide
      direct support for targeting IL-10 as an approach to therapy in human VL.

PMID- 21881131
TI  - Genetic variation in the dectin-1/CARD9 recognition pathway and susceptibility to
      candidemia.
AB  - BACKGROUND: Candidemia is an important cause of morbidity and mortality in
      critically ill patients or patients undergoing invasive treatments. Dectin-1 is
      the main beta-glucan receptor, and patients with a complete deficiency of either
      dectin-1 or its adaptor molecule CARD9 display persistent mucosal infections with
      Candida albicans. The role of genetic variation of DECTIN-1 and CARD9 genes on
      the susceptibility to candidemia is unknown. METHODS: We assessed whether genetic
      variation in the genes encoding dectin-1 and CARD9 influence the susceptibility
      to candidemia and/or the clinical course of the infection in a large cohort of
      American and Dutch candidemia patients (n = 331) and noninfected matched controls
      (n = 351). Furthermore, functional studies have been performed to assess the
      effect of the DECTIN-1 and CARD9 genetic variants on cytokine production in vitro
      and in vivo in the infected patients. RESULTS: No significant association between
      the single-nucleotide polymorphisms DECTIN-1 Y238X and CARD9 S12N and the
      prevalence of candidemia was found, despite the association of the DECTIN-1 238X
      allele with impaired in vitro and in vivo cytokine production. CONCLUSIONS:
      Whereas the dectin-1/CARD9 signaling pathway is nonredundant in mucosal immunity
      to C. albicans, a partial deficiency of beta-glucan recognition has a minor
      impact on susceptibility to candidemia.

PMID- 21881132
TI  - Acinetobacter baumannii resistant to colistin with impaired virulence: a case
      report from France.

PMID- 21881133
TI  - Acinetobacter baumannii resistant to colistin alters its antibiotic resistance
      profile: a case report from Spain.

PMID- 21881135
TI  - Geometrical constraints in the scaling relationships between genome size, cell
      size and cell cycle length in herbaceous plants.
AB  - Plant nuclear genome size (GS) varies over three orders of magnitude and is
      correlated with cell size and growth rate. We explore whether these relationships
      can be owing to geometrical scaling constraints. These would produce an isometric
      GS-cell volume relationship, with the GS-cell diameter relationship with the
      exponent of 1/3. In the GS-cell division relationship, duration of processes
      limited by membrane transport would scale at the 1/3 exponent, whereas those
      limited by metabolism would show no relationship. We tested these predictions by
      estimating scaling exponents from 11 published datasets on differentiated and
      meristematic cells in diploid herbaceous plants. We found scaling of GS-cell size
      to almost perfectly match the prediction. The scaling exponent of the
      relationship between GS and cell cycle duration did not match the prediction.
      However, this relationship consists of two components: (i) S phase duration,
      which depends on GS, and has the predicted 1/3 exponent, and (ii) a GS
      independent threshold reflecting the duration of the G1 and G2 phases. The
      matches we found for the relationships between GS and both cell size and S phase
      duration are signatures of geometrical scaling. We propose that a similar
      approach can be used to examine GS effects at tissue and whole plant levels.

PMID- 21881136
TI  - Promiscuous mating produces offspring with higher lifetime fitness.
AB  - In many species, each female pairs with a single male for the purpose of rearing
      offspring, but may also engage in extra-pair copulations. Despite the prevalence
      of such promiscuity, whether and how multiple mating benefits females remains an
      open question. Multiple mating is typically thought to be favoured primarily
      through indirect benefits (i.e. heritable effects on the fitness of offspring).
      This prediction has been repeatedly tested in a variety of species, but the
      evidence has been equivocal, perhaps because such studies have focused on pre
      reproductive survival rather than lifetime fitness of offspring. Here, we show
      that in a songbird, the dark-eyed junco (Junco hyemalis), both male and female
      offspring produced by extra-pair fertilizations have higher lifetime reproductive
      success than do offspring sired within the social pair. Furthermore, adult male
      offspring sired via extra-pair matings are more likely to sire extra-pair
      offspring (EPO) themselves, suggesting that fitness benefits to males accrue
      primarily through enhanced mating success. By contrast, female EPO benefited
      primarily through enhanced fecundity. Our results provide strong support for the
      hypothesis that the evolution of extra-pair mating by females is favoured by
      indirect benefits and shows that such benefits accrue much later in the
      offspring's life than previously documented.

PMID- 21881137
TI  - On the analysis of risk-sensitive foraging: a comment on Codding et al.

PMID- 21881138
TI  - Adaptive evolution of sexual systems in pedunculate barnacles.
AB  - How and why diverse sexual systems evolve are fascinating evolutionary questions,
      but few empirical studies have dealt with these questions in animals. Pedunculate
      (gooseneck) barnacles show such diversity, including simultaneous
      hermaphroditism, coexistence of dwarf males and hermaphrodites (androdioecy), and
      coexistence of dwarf males and females (dioecy). Here, we report the first
      phylogenetically controlled test of the hypothesis that the ultimate cause of the
      diverse sexual systems and presence of dwarf males in this group is limited
      mating opportunities for non-dwarf individuals, owing to mating in small groups.
      Within the pedunculate barnacle phylogeny, dwarf males and females have evolved
      repeatedly. Females are more likely to evolve in androdioecious than
      hermaphroditic populations, suggesting that evolution of dwarf males has preceded
      that of females in pedunculates. Both dwarf males and females are associated with
      a higher proportion of solitary individuals in the population, corroborating the
      hypothesis that limited mating opportunities have favoured evolution of these
      diverse sexual systems, which have puzzled biologists since Darwin.

PMID- 21881139
TI  - Sleep apnoea syndrome: how will physiologic knowledge position personalised
      medicine?

PMID- 21881140
TI  - A first step against idiopathic pulmonary fibrosis.

PMID- 21881141
TI  - Idiopathic pulmonary fibrosis: present understanding and future options.

PMID- 21881142
TI  - Sleep apnoea syndrome in 2011: current concepts and future directions.

PMID- 21881143
TI  - Physiological techniques for detecting expiratory flow limitation during tidal
      breathing.
AB  - Patients with severe chronic obstructive pulmonary disease (COPD) often exhale
      along the same flow-volume curve during quiet breathing as they do during the
      forced expiratory vital capacity manoeuvre, and this has been taken as an
      indicator of expiratory flow limitation at rest (EFL(T)). Therefore, EFL(T),
      namely attainment of maximal expiratory flow during tidal expiration, occurs when
      an increase in transpulmonary pressure causes no increase in expiratory flow.
      EFL(T) leads to small airway injury and promotes dynamic pulmonary
      hyperinflation, with concurrent dyspnoea and exercise limitation. In fact, EFL(T)
      occurs commonly in COPD patients (mainly in Global Initiative for Chronic
      Obstructive Lung Disease III and IV stage), in whom the latter symptoms are
      common, but is not exclusive to COPD, since it can also be detected in other
      pulmonary and nonpulmonary diseases like asthma, acute respiratory distress
      syndrome, heart failure and obesity, etc. The existing up to date physiological
      techniques of assessing EFL(T) are reviewed in the present work. Among the
      currently available techniques, the negative expiratory pressure has been
      validated in a wide variety of settings and disorders. Consequently, it should be
      regarded as a simple, noninvasive, practical and accurate new technique.

PMID- 21881144
TI  - Pulmonary aspergillosis: a clinical review.
AB  - Aspergillus is a mould which may lead to a variety of infectious, allergic
      diseases depending on the host's immune status or pulmonary structure. Invasive
      pulmonary aspergillosis occurs primarily in patients with severe
      immunodeficiency. The significance of this infection has dramatically increased
      with growing numbers of patients with impaired immune state associated with the
      management of malignancy, organ transplantation, autoimmune and inflammatory
      conditions; critically ill patients and those with chronic obstructive pulmonary
      disease appear to be at an increased risk. The introduction of new noninvasive
      tests, combined with more effective and better-tolerated antifungal agents, has
      resulted in lower mortality rates associated with this infection. Chronic
      necrotising aspergillosis is a locally invasive disease described in patients
      with chronic lung disease or mild immunodeficiency. Aspergilloma is usually found
      in patients with previously formed cavities in the lung, whereas allergic
      bronchopulmonary aspergillosis, a hypersensitivity reaction to Aspergillus
      antigens, is generally seen in patients with atopy, asthma or cystic fibrosis.
      This review provides an update on the evolving epidemiology and risk factors of
      the major manifestations of Aspergillus lung disease and the clinical
      manifestations that should prompt the clinician to consider these conditions.
      Current approaches for the diagnosis and management of these syndromes are
      discussed.

PMID- 21881145
TI  - Beyond corticosteroids: future prospects in the management of inflammation in
      COPD.
AB  - Inflammation plays a central role in the pathophysiology of chronic obstructive
      pulmonary disease (COPD). Exposure to cigarette smoke induces the recruitment of
      inflammatory cells in the airways and stimulates innate and adaptive immune
      mechanisms. Airway inflammation is involved in increased bronchial wall
      thickness, increased bronchial smooth muscle tone, mucus hypersecretion and loss
      of parenchymal elastic structures. Oxidative stress impairs tissue integrity,
      accelerates lung ageing and reduces the efficacy of corticosteroids by decreasing
      levels of histone deacetylase-2. Protease-antiprotease imbalance impairs tissues
      and is involved in inflammatory processes. Inflammation is also present in the
      pulmonary artery wall and at the systemic level in COPD patients, and may be
      involved in COPD-associated comorbidities. Proximal airways inflammation
      contributes to symptoms of chronic bronchitis while distal and parenchymal
      inflammation relates to airflow obstruction, emphysema and hyperinflation. Basal
      levels of airways and systemic inflammation are increased in frequent
      exacerbators. Inhaled corticosteroids are much less effective in COPD than in
      asthma, which relates to the intrinsically poor reversibility of COPD-related
      airflow obstruction and to molecular mechanisms of resistance relating to
      oxidative stress. Ongoing research aims at developing new drugs targeting more
      intimately COPD-specific mechanisms of inflammation, hypersecretion and tissue
      destruction and repair. Among new anti-inflammatory agents, phosphodiesterase-4
      inhibitors have been the first to emerge.

PMID- 21881146
TI  - Night-time symptoms: a forgotten dimension of COPD.
AB  - Sleep quality is often poor in patients with chronic obstructive pulmonary
      disease (COPD), but these night-time symptoms are frequently unnoticed by
      physicians and/or not reported by patients themselves. Therefore, the prevalence
      and clinical impact of sleep disturbances and night-time symptoms in COPD is not
      well understood and has not been a clinical focus to date. To address this gap,
      an expert panel meeting was convened in Barcelona, Spain, in March 2011 to
      discuss the aetiology, evolution, burden, long-term clinical consequences and
      optimal management of night-time symptoms in COPD. The term "night-time symptoms"
      in COPD has not been distinctly defined in an objective sense but epidemiological
      data suggests that the prevalence of nocturnal symptoms and symptomatic sleep
      disturbance may exceed 75% in patients with COPD. The panel concluded that night
      time symptoms in COPD are prevalent and bothersome; that their cause(s) are
      multiple and include demographic factors, such as age and obesity,
      pharmacotherapy, disease-specific symptoms and the presence of comorbid sleep
      disorders, and other medical conditions; and that potential long-term
      consequences can include lung function changes, increased exacerbation frequency,
      emergence or worsening of cardiovascular disease, cognitive effects, depression,
      impaired quality of life and increased mortality. To date, few interventional
      studies have investigated them, but emerging data suggest that bronchodilator
      therapy can improve them if deployed appropriately. In summary, night-time
      symptoms in COPD warrant further clinical investigation with validated tools.

PMID- 21881147
TI  - Challenges in idiopathic pulmonary fibrosis trials: the point on end-points.
AB  - Idiopathic pulmonary fibrosis (IPF) is the most common of the idiopathic
      interstitial pneumonias and is associated with both a variable clinical course
      and a poor prognosis. Investigators involved in clinical trials and clinicians
      reviewing the IPF literature are confronted with daunting challenges in selecting
      reliable outcome measures, interpreting the clinical and statistical importance
      of these findings, and applying this knowledge to the clinical care of their
      patients. In order to evaluate the efficacy of new treatment regimens, a number
      of studies have been performed, employing a range of clinical and surrogate end
      points. In most studies, the primary end-point consists of a single outcome
      measure. A desirable single clinical end-point for IPF should be reliable, valid,
      responsive to changes in disease status, clinically meaningful, predictive of
      clinical outcome and responsive to treatment effect of a given intervention.
      Proper consideration and effective choice of outcome measures used in IPF studies
      will help establish effective and achievable drug development programmes and will
      enable clinicians and investigators to make informed critical decisions in
      recommending a treatment regimen to their IPF patients.

PMID- 21881148
TI  - Emerging potential treatments: new hope for idiopathic pulmonary fibrosis
      patients?
AB  - Currently, there are no approved pharmacological treatments for the management of
      patients with idiopathic pulmonary fibrosis (IPF) in the USA or Europe.
      Pirfenidone is an orally bio-available small molecule that exhibits antifibrotic
      and anti-inflammatory properties in a variety of in vitro and animal models.
      Pirfenidone has been evaluated in four randomised, double-blind, placebo
      controlled clinical trials conducted in Japan, North America and Europe. The
      totality of the data from these trials indicates that pirfenidone is able to
      reduce the rate of decline in lung function, measured as change in per cent
      predicted forced vital capacity (FVC) or vital capacity. There was also an effect
      on secondary end-points of progression free survival, categorical change in per
      cent predicted FVC, and the 6-min walk test. A recent meta-analysis of the three
      phase III studies in IPF demonstrated that pirfenidone significantly reduced the
      risk of disease progression by 30%. The efficacy of pirfenidone is associated
      with an acceptable tolerability and safety profile.

PMID- 21881149
TI  - Pulmonary lymphangitic carcinomatosis presenting as severe interstitial lung
      disease in a 15-year-old female.

PMID- 21881150
TI  - Pulmonary nocardiosis in immunocompetent patients: can COPD be the only risk
      factor?

PMID- 21881151
TI  - Optimizing the Wingate Anaerobic Cycling Test for youth with juvenile idiopathic
      arthritis.
AB  - The Wingate Anaerobic Test (WAnT) can assess muscle function in youth with
      juvenile idiopathic arthritis (JIA). Our objective was to compare peak power (PP)
      and mean power (MP) when the WAnT is performed with a standard vs. an optimized
      braking force. Eight patients with JIA between the ages of 8 and 18 participated
      in two sessions. Optimal braking force was determined with a series of 15-s force
      velocity tests performed against braking forces ranging from 3.5 to 8.5% of body
      weight. Participants then performed two randomized WAnTs against the standard
      (4.5%) and optimal braking forces. PP tended to be greater in the optimized vs.
      standard WAnT (12.5 +/- 2.6 vs. 10.8 +/- 1.0 W/kg, respectively; p = .07). No
      differences were observed for MP (standard: 6.2 +/- 0.9 vs. optimized: 6.2 +/-
      1.1 W/kg; p = .9). Optimization of the WAnT tended to increase PP by 10-28% in
      youth with JIA.

PMID- 21881152
TI  - Effect of rest interval on neuromuscular and metabolic responses between children
      and adolescents.
AB  - The purpose of this study was to compare the effect of different rest intervals
      and contraction velocities on muscle recovery following resistance exercise. 18
      children (11.1 +/- 0.52 yrs) and 19 adolescents (15.8 +/- 0.49 yrs) performed
      three sets of 10 isokinetic repetitions at 60 degrees /s and 180 degrees /s. The
      work-to-rest ratio (W/R) was 1:2 and 1:4 for 60 degrees /s, and 1:6 and 1:12 for
      180 degrees /s. ANOVA revealed that children demonstrated no significant decline
      in PT from the first to third set with any rest interval, but there was a
      significant (p < .05) decline for adolescents when a W/R of 1:2, 1:4 and 1:6 were
      used. Adolescents demonstrated significantly greater blood lactate (BLa)
      concentrations than children after three sets of resistance exercise. The present
      study indicates that adolescents may require longer rest intervals to recover
      full PT when compared with children.

PMID- 21881153
TI  - Relationship between active school transport and body mass index in grades 4-to-6
      children.
AB  - The current investigation assessed the impact of active school transportation
      (AST) on average daily step counts, body mass index (BMI) and waist circumference
      in 315 children in Grades 4-6 who participated to Cycle 2 of the Canadian
      Assessment of Physical Literacy (CAPL) pilot testing. T-tests revealed a
      significant association between AST and lower BMI values (18.7 +/- 3.3 vs. 19.9
      +/- 3.8 kg/m(2)). The active commuters accumulated an average of 662 more steps
      per day, and their waist circumference was lower by an average of 3.1 cm, but
      these differences were not statistically significant. ANCOVA analyses controlling
      for age and step counts, found trends toward lower BMI and waist circumference
      values among the active commuters. These results suggest that AST may be a valid
      strategy to prevent childhood obesity; further research is needed to determine
      more precisely the impact of AST on body composition, and the direction of the
      relationship.

PMID- 21881154
TI  - Changes in physical activity, self-efficacy and depressive symptoms in adolescent
      girls.
AB  - The purpose of this study was to examine the longitudinal relationships between
      naturally occurring changes in leisure-time physical activity, depressive
      symptoms and self-efficacy in adolescent girls. We also aimed to test whether
      depressive symptoms would moderate the self-efficacy-physical activity
      relationship. Participants were 181 urban adolescent girls. Physical activity was
      measured using the 3-Day Physical Activity Recall. Self-efficacy and depressive
      symptoms were assessed using questionnaires. Body height and body mass were
      measured and body mass index (BMI) was calculated. Data were collected on three
      occasions over a 2-year period. There was a decrease in physical activity and
      self-efficacy and increase in depressive symptoms across three measurement
      occasions. There were statistically significant and negative relationships
      between initial level and change for physical activity and depressive symptoms.
      Initially higher levels of physical activity were related with initially lower
      levels of depressive symptoms, and change in physical activity across time was
      inversely associated with change in levels of depressive symptoms across
      measurements. There were statistically significant and positive relationships
      between initial level and change for physical activity and self-efficacy after
      controlling effect of BMI. Latent growth modeling (LGM) also indicated a
      moderating effect of depressive symptoms on the self-efficacy-physical activity
      relationship. Girls who had high initial levels of self-efficacy and smaller
      increases in depressive symptoms had the lowest decline in physical activity
      participation. Our results encourage the design of interventions that reduce
      depressive symptoms and increase self-efficacy as a possible of means of
      increasing adolescent girls' physical activity.

PMID- 21881155
TI  - The effect of pre-exercise carbohydrate supplementation on anaerobic exercise
      performance in adolescent males.
AB  - Carbohydrate (CHO) consumption before anaerobic exercise was studied in 13
      adolescent boys (15.2 +/- 0.9 yrs). A within subjects design was employed where
      subjects consumed a 22% CHO or volume-matched placebo (PL) beverage 30-min before
      anaerobic exercise on two separate days. Exercise consisted of a Wingate
      Anaerobic Test (WAnT), ten by 10-s-sprints, and a second WAnT. Fatigue index and
      peak power (PP) were similar while mean power (MP) was higher (p < .025) in CHO
      trial; however this difference was ascribed to initial WAnT performance. PP and
      MP for the 10-s sprints were similar between trials. Intravenous blood glucose
      and insulin concentrations were higher (p < .05) in the CHO trial while lactate
      and catecholamine concentrations were similar. Improved performance on a single
      WAnT was apparent with CHO consumption before exercise; however, this strategy
      did not attenuate fatigue over time in adolescent boys.

PMID- 21881156
TI  - Validity of the Actical accelerometer step-count function in children.
AB  - This study sought to assess criterion validity of the Actical monitor step-count
      function in children via ankle and waist placement, compared with observed video
      recordings. Children attending a summer program (12 boys, 7 girls, mean age =
      9.6yrs, range 7-11yrs) wore two synchronized Acticals, attached at the ankle (AA)
      and waist (AW). Children performed treadmill walking at varying speeds, and two
      research assistants counted steps using observed video recordings (OVR). Results
      showed high correlations for AW-OVR (r = .927, p < .001) and AA-OVR (r = .854, p
      < .001), but AW and AA were significantly lower than OVR (t > 11.2, p < .001). AW
      provided better step estimates than AA for step rates above 130 steps per minute.
      In contrast, AA was superior to AW for slow walking, and measured more steps
      during the (nontreadmill) program time. Overall, the Actical monitor showed good
      evidence of validity as a measure of steps in children for population-based
      studies.

PMID- 21881157
TI  - Within- and between-day variability of objectively measured physical activity in
      preschoolers.
AB  - In this study, physical activity (PA) was objectively measured in 213 Belgian
      preschoolers (M(age) = 4.98, SD = .88 years) over 4 consecutive days including
      two weekend days. Within-day variability in PA showed a typical activity pattern
      during weekdays and weekend days. Weekdays clearly reflected a preschool
      attending day with more peaks and troughs than weekend days and after-school
      hours were characterized by a decrease in activity. Between-day variability in PA
      was identified in preschool girls above the age of four, suggesting that the lack
      of a structured preschool environment is already related with a decrease in PA in
      this sex-specific age group. The results of this study are informative for the
      development of future PA interventions and indicate that both the preschool and
      the home environment should be targeted in the promotion of preschoolers' PA.

PMID- 21881158
TI  - The influence of body composition on youth throwing kinetics.
AB  - The primary objective of this study was to investigate the influence of segmental
      mass and body composition on the upper extremity biomechanics of overweight youth
      participating in baseball activities. The study used a regression framework to
      investigate the relationship between whole body, throwing arm segmental mass and
      body composition measures to kinetic variables about the shoulder and elbow. The
      multivariate regression results indicated a strong positive significant
      relationship between each of the mass variables to that of the moment variables
      about the shoulder and elbow. Participants who had a greater percentage of fat
      mass produced greater injury correlated moments about the shoulder and elbow.

PMID- 21881159
TI  - SCUBA-dive-related changes in heart rate in children.
AB  - The purpose of this study was to monitor heart rate (HR) and rhythm during open
      water SCUBA dives. Nine children performed 25-min open water SCUBA dives to 8 m
      depth. Before, during and after these dives, ECG was recorded. Compared with
      predive heart rate, heart rate declined by -24 +/- 8% (range -36%; -15%) during
      the dive. In some children a further decline in HR was observed within the last
      minutes of the dive. Older and taller subjects and those with a high initial HR
      showed a more pronounced decline in HR. Furthermore singular supraventricular and
      ventricular extrasystoles were observed in some children. Immersion as well as
      facial and skin cooling presumably account for the initial decline in heart rate.
      A further drop in HR within the last minutes of the dive might be related to mild
      hypothermia. Single supraventricular and ventricular extrasystoles might occur in
      healthy children during dives.

PMID- 21881160
TI  - Convergent validity of a piezoelectric pedometer and an omnidirectional
      accelerometer for measuring children's physical activity.
AB  - The aim of this study was to assess the convergent validity of a new
      piezoelectric pedometer and an omnidirectional accelerometer for assessing
      children's time spent in moderate to vigorous physical activity (MVPA).A total of
      114 children (51 boys, 63 girls) aged 5-11 years wore a sealed NL-1000
      piezoelectric pedometer (New Lifestyles Inc, Lee's Summit, MO) and an Actical
      accelerometer (Mini Mitter, Bend, OR) over one school day. The NL-1000 pedometers
      were randomized to one of two manual intensity thresholds used to define MVPA
      (1): Level 3 = 2.9 metabolic equivalent test (MET) and (2) Level 4 = 3.6 MET.
      Compared with the Actical, the NL-1000 underestimated the time spent in MVPA by
      37% and 45% at intensity levels 3 and 4, respectively. In addition, the 95%
      limits of agreement were wide at both intensity levels (level 3 = -144%, 70%;
      level 4 = -135%, 45%), indicating a low level of precision.

PMID- 21881161
TI  - The interaction of obesity and puberty on substrate utilization during exercise:
      a gender comparison.
AB  - The study evaluated the interactions of puberty and obesity on substrate
      oxidation of overweight girls (n = 38) and boys (N = 35; BMI > 85th percentile)
      matched for gender, age, and puberty (pre/pubertal) with normal weight girls and
      boys. Metabolic rates (VO(2)) were obtained during rest and at 4, 5.6 and 8 k/h.
      Carbohydrate oxidation rates (mg/kgFFM/min) adjusted for % predicted VO(2max),
      were higher for prepubertal OW children than pubertal children (p < .03). Fat
      oxidation rates were higher for NW prepubertal boys compared with other boys.
      Results indicate that OW children, regardless of gender or pubertal status,
      increase their carbohydrate oxidation rate to compensate for higher than normal
      metabolic rates. The effects of obesity on the substrate use is marginally
      related to puberty.

PMID- 21881162
TI  - This recession is wearing me out! Health-related quality of life and economic
      downturns.
AB  - BACKGROUND: Health-related quality of life refers to an individual's perceived
      physical and mental health and goes beyond the presence or absence of illnesses
      to encompass a multidimensional concept of well being. Previous research on the
      relationships between macroeconomic conditions and health status reveal
      improvements in physical health during economic downturns. However, few studies
      have examined whether mental health status improves or declines during tough
      economic times. AIMS: The main objective of this paper is to provide new evidence
      on the impact of macroeconomic conditions on Health-related quality of life
      (HRQL), or functional health, by analyzing the physical and mental health summary
      scores of the 12-Item Short Form Health Survey (SF-12). DATA: The analysis uses
      panel data from Waves 1 and 2 of the National Epidemiological Survey of Alcohol
      and Related Conditions (NESARC) for individuals 18-59 years (in Wave 1), for a
      final sample of 26,313 individuals. The NESARC collected and reported data on the
      SF-12 health scores, including a physical health score (PCS) for overall physical
      functioning, and a mental health score (MCS) for mental/psychological
      functioning. To analyze the impact of economic downturns on HRQL, the study
      matches the NESARC variables with data on state-level macroeconomic conditions.
      METHODS: To estimate the effects of macroeconomic conditions on HRQL, this paper
      takes advantage of the longitudinal nature of the dataset and uses individual
      fixed-effect models to account for both individual and state-level heterogeneity.
      Although it is unlikely for individual omitted variables (e.g., individuals'
      preferences and attitudes) to be significantly correlated with the state
      unemployment rate, using longitudinal data allows for the estimation of a more
      fully specified model. RESULTS: Findings consistently indicate that an increase
      in the average state unemployment rate worsens an individual's HRQL, suggesting
      that the loss of jobs and income and/or the economic distress associated with
      economic downturns have a detrimental effect on people's daily lives. Although
      the magnitudes of the changes are generally small, results show that mental
      health decreases more than physical health during tough economic times. POLICY
      IMPLICATIONS: With the recent worldwide economic recession causing steep drops in
      the U.S. Gross Domestic Product along with double-digit unemployment rates, the
      implications of this study are disheartening. Besides macroeconomic policies to
      help stimulate the economy, government officials and policymakers should also
      consider social policies to help people cope with the recession and buffer the
      potential negative health impact, both mental and physical. Moreover,
      policymakers should keep in mind that the mental health effects might be greater
      and longer lasting.

PMID- 21881163
TI  - Pursuing cost-effectiveness in mental health service delivery for youth with
      complex needs.
AB  - BACKGROUND: Mental health advocates seek to expand children's services, noting
      widespread failure to meet the needs of public sector youth suffering from
      serious emotional disturbance (SED). However, state and national budgets face
      deepening cuts, with rising health care costs taking the blame. As the gap
      between needs and finances widens, identification of cost-effective treatments
      that will benefit children with SED and their families is of increasing
      importance. Community-based interventions for this population, such as the
      wraparound approach and systems-of-care, are being disseminated but literature is
      scant regarding effects on expense. The Mental Health Services Program for Youth
      (MHSPY) model is aligned philosophically with wraparound and systems-of-care but
      unique in blending public agency dollars to deliver integrated medical, mental
      health and social services. MHSPY's linked clinical and expense data is useful to
      study community-based treatment cost-effectiveness. AIMS OF STUDY: To examine the
      cost-effectiveness of an intensively integrated, family and community-based
      clinical intervention for youth with mental health needs in comparison to "usual
      care.'' METHODS: Study and reference populations were matched on age, gender,
      community, psychiatric diagnosis, morbidity and insurance type. Claims analyses
      included patterns of service utilization and medical expense for both groups.
      Using propensity score matching, results for study youth are compared with
      results for the population receiving "usual care.'' Clinical functioning was
      measured for the intervention group at baseline and 12 months. RESULTS: The
      intervention group used lower intensity services and had substantially lower
      claims expense (e.g. 32% lower for emergency room, 74% lower for inpatient
      psychiatry) than their matched counterparts in the "usual care'' group.
      Intervention youth were consistently maintained in least restrictive settings,
      with over 88% of days spent at home and showed improved clinical functioning on
      standard measures. DISCUSSION: The intensive MHSPY model of service delivery
      offers potential as a cost-effective intervention for complex youth. Its
      integrated approach, recognizing needs across multiple life domains, appears to
      enhance engagement and the effectiveness of mental health treatment, resulting in
      statistically significant clinical improvements. Functional measures are not
      collected in "usual care,'' limiting comparisons. However, claims expense for
      intervention youth was substantially lower than claims expense for Medicaid
      comparison youth, suggesting clinical needs for intervention youth post
      enrollment were lower than for those receiving "usual care.'' IMPLICATIONS FOR
      HEALTH CARE PROVISION AND USE: The MHSPY model, which intentionally engages
      families in "clustered'' traditional and non-traditional services, represents a
      replicable strategy for enhancing the impact of clinical interventions, thereby
      reducing medical expense. IMPLICATIONS FOR HEALTH POLICIES: Blending categorical
      state agency dollars and insurance funds creates flexibility to support community
      based care, including individualized services for high-risk youth. Resulting
      expenses total no more, and are often less, than "treatment as usual'' but yield
      greater clinical benefits. IMPLICATIONS FOR FURTHER RESEARCH: Further research is
      needed regarding which intervention elements contribute the most towards improved
      clinical functioning, as well as which patients are most likely to benefit. A
      randomized trial of MHSPY vs. "usual care,'' including examination of the
      sustainability of effects post-disenrollment, would provide a chance to further
      test this innovative model.

PMID- 21881164
TI  - Costs for patients with psychotic illness: differences depending upon state of
      remission.
AB  - BACKGROUND: Psychotic illnesses have a substantial economic burden on patients,
      family members, friends, and society in general, still there have been limited
      attempts to estimate the costs associated with this condition. Moreover, nothing
      is known about the differences in costs between patients depending on disease
      severity, i.e. state of remission. AIM: Estimate the direct and indirect costs
      for a defined patient population with psychotic illness in Sweden, and
      demonstrate differences in direct costs depending on disease severity (state of
      remission). MATERIALS AND METHODS: The cost analyses are based on data from the
      Clinical Long-term Investigation of Psychosis in Sweden (CLIPS), which is an
      ongoing, single-centre, epidemiological study. Resource use and disease severity
      were captured for the patients during one year, 2007. Total costs per patients
      are estimated and cost differences between patients, depending on state of
      remission, are considered. RESULTS: 199 patients with a mean age of 51 (63% men)
      were followed for 12 months. They had a mean of 6.4 inpatient-days, 1.4 physician
      visits, 18.6 nurse visits, 1.2 counsellor visits and 6.3 visits to other staff
      including tests and diagnostic procedures per patient- year. The mean total cost
      (direct and indirect) amounted to 62,500 per patient and year. Patients in steady
      state of remission had lower direct costs compared to other patients. Moreover,
      the size of the various cost items differed between patients' depending on state
      of remission. Patients in steady remission had almost no inpatient costs.
      DISCUSSION: For a comprehensive assessment of treatment of psychotic illnesses it
      is necessary to provide evidence of the costs related to disease severity. We
      find that patients suffering from psychotic illness have varying costs depending
      on their disease severity, and this study indicates that if patients can be kept
      in remission direct costs will decrease. We can also confirm that reallocation
      has taken place the last 15 years, between different cost items, from in-patient
      care at hospitals to out-patient care and assistance at home. LIMITATIONS:
      Information about informal care was collected from patients and not from informal
      carers themselves. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: Costs have
      been reallocated from in-patient care to costs for assistance at home, which is a
      reflection of the change in care of patients with mental problems that has taken
      place during the last 15 years. Patients in steady remission have lower costs
      compared to patients in steady non-remission or patients switching between the
      two states. A better surveillance of the disorder would lead to lower direct, as
      well as indirect, costs.

PMID- 21881165
TI  - Mental health care and out-of-pocket expenditures in Europe: results from the
      ESEMeD project.
AB  - BACKGROUND: Most published data on out-of-pocket spending on mental health
      originate from the United States, where insurance payments for mental health have
      traditionally been much less generous than benefits for other health care
      services. Given the difference in the structure of health care funding in Europe,
      it is clearly important to obtain similar information on out-of-pocket
      expenditure in different European countries. AIM OF THE STUDY: To estimate out-of
      pocket costs paid by people who receive mental health care in six European
      countries (Belgium, France, Germany, Italy, the Netherlands, and Spain). METHODS:
      Of the 8,796 participants in a cross-sectional survey conducted in these six
      European countries, 1,128 reported having consulted a professional for a mental
      health problem in the year preceding the interview and provided information on
      how many times in the past year they consulted each type of provider, and the
      money they and their family members had paid out-of-pocket for their mental
      health care. In addition to sociodemographic characteristics, information on
      mental health status was collected using the CIDI 3.0. Descriptive statistics on
      out-of-pocket expenditure and share of income across countries were generated.
      Two-part models were employed to identify the relationship between the different
      covariates, notably the types of providers consulted, and out-of-pocket
      expenditure. RESULTS: Overall, 41.0% of those who used services for a mental
      health problem paid something for the care they received. This represented a
      minority of respondents in all countries except Belgium (87.9%) and Italy
      (61.7%). The financial burden of these costs relative to income was found to be
      low (1.2%), ranging from 0.4% in Germany to 2.3% in France. Out-of-pocket
      expenditure differed according to the type of providers consulted, with non
      physician health professionals and medical specialists being more often
      associated with significant expenditure. DISCUSSION AND LIMITATIONS: Although the
      study is limited principally by data collection from self-report, it is the first
      of its kind, to our knowledge, and suggests that out-of-pocket costs for mental
      health care in Europe are relatively low compared to the United States. However,
      differences between countries exist, which may be partially due to differences in
      coverage for specialized care. IMPLICATIONS FOR HEALTH POLICIES: Consultations
      with non-physician mental health professionals such as psychologists are
      expensive for patients, since they are reimbursed to a lesser extent than
      consultations with physicians, or not reimbursed at all. This limits their role
      and increases the burden on psychiatrists. IMPLICATIONS FOR FURTHER RESEARCH:
      Monitoring out-of-pocket spending on mental health, preferably on the basis of
      administrative data when available, is essential in the current context of cost
      containment policy, where out-of-pocket spending may be expected to increase.

PMID- 21881166
TI  - GMB: an efficient query processor for biological data.
AB  - Bioinformatics applications manage complex biological data stored into
      distributed and often heterogeneous databases and require large computing power.
      These databases are too big and complicated to be rapidly queried every time a
      user submits a query, due to the overhead involved in decomposing the queries,
      sending the decomposed queries to remote databases, and composing the results.
      There is also considerable communication costs involved. This study addresses the
      mentioned problems in Grid-based environment for bioinformatics. We propose a
      Grid middleware called GMB that alleviates these problems by caching the results
      of Frequently Used Queries (FUQ). Queries are classified based on their types and
      frequencies. FUQ are answered from the middleware, which improves their response
      time. GMB acts as a gateway to TeraGrid Grid: it resides between users&rsquo;
      applications and TeraGrid Grid. We evaluate GMB experimentally.

PMID- 21881168
TI  - Bioprinting cell-laden matrigel for radioprotection study of liver by pro-drug
      conversion in a dual-tissue microfluidic chip.
AB  - The objective of this paper is to introduce a novel cell printing and
      microfluidic system to serve as a portable ground model for the study of drug
      conversion and radiation protection of living liver tissue analogs. The system is
      applied to study behavior in ground models of space stress, particularly
      radiation. A microfluidic environment is engineered by two cell types to prepare
      an improved higher fidelity in vitro micro-liver tissue analog. Cell-laden
      Matrigel printing and microfluidic chips were used to test radiation shielding to
      liver cells by the pro-drug amifostine. In this work, the sealed microfluidic
      chip regulates three variables of interest: radiation exposure, anti-radiation
      drug treatment and single- or dual-tissue culture environments. This application
      is intended to obtain a scientific understanding of the response of the multi
      cellular biological system for long-term manned space exploration, disease models
      and biosensors.

PMID- 21881169
TI  - DFT study on magnetic interaction in an orbitally degenerate Ti3+ dimer complex.
AB  - The magnetic interaction in an orbitally degenerate transition metal dimer
      complex is investigated using a typical example of a d(1)-d(1) dimer complex, the
      Ti2Cl9(3-) cluster. The local orbital functions are defined by linear
      combinations of the molecular orbital functions which are calculated by density
      functional theory (DFT). In the DFT calculation, the Perdew-Burke-Ernzerhof (PBE)
      functional and hybrid PBE0 functional are utilized. The matrix elements of the
      effective Hamiltonian of the d-electrons are evaluated by the DFT calculation
      except for one parameter which is determined by comparing the zero-temperature
      magnetic susceptibility in the direction along the c axis chi(?) with the
      experimental result. By the calculation with the PBE0 functional, the zero
      temperature magnetic susceptibility in the perpendicular direction chi(?) and the
      temperature dependence of the susceptibilities in both directions agree with the
      experiment. On the other hand, by the calculation with the PBE functional, chi(?)
      is smaller than the experimental values because the on-site potential is
      underestimated.

PMID- 21881170
TI  - Magnetothermoelectric transport in modulated and unmodulated graphene.
AB  - We draw motivation from recent experimental studies and present a comprehensive
      study of magnetothermoelectric transport in a graphene monolayer within the
      linear response regime. We employ the modified Kubo formalism developed for
      thermal transport in a magnetic field. Thermopower as well as thermal
      conductivity as a function of the gate voltage of a graphene monolayer in the
      presence of a magnetic field perpendicular to the graphene plane is determined
      for low magnetic fields (~1 T) as well as high fields (~8 T). We include the
      effects of screened charged impurities on thermal transport. We find good
      qualitative and quantitative agreement with recent experimental work on the
      subject. In addition, in order to analyze the effects of modulation, which can be
      induced by various means, on the thermal transport in graphene, we evaluate the
      thermal transport coefficients for a graphene monolayer subjected to a periodic
      electric modulation in a magnetic field. The results are presented as a function
      of the magnetic field and the gate voltage.

PMID- 21881172
TI  - A vanadyl Schiff base complex: {2,2'-[1,1'-(o-phenylenedinitrilo)bis(ethan-1-yl-1
      ylidene)]diphenolato}oxovanadium(IV).
AB  - The green crystals of the title compound, [V(C(22)H(18)N(2)O(2))O], represent a
      mononuclear oxovanadium complex. The central V(IV) centre has a distorted square
      pyramidal coordination. Two N atoms and two O atoms of the Schiff base ligand
      define the base of the pyramid, and the oxide O atom is in the apical position.
      Density functional theory (DFT) calculations were performed to analyse the
      changes in the geometry of the ligand during the complex formation. The most
      significant changes are observed in the values of the torsion angles in the
      vicinity of the donor N atoms. The HOMA index (Harmonic Oscillator Model of
      Aromaticity) has been calculated to compare the aromaticity of the benzene rings
      in the complex and its ligand.

PMID- 21881171
TI  - The effect of isoflurane anesthesia on the electroencephalogram assessed by
      harmonic wavelet bicoherence-based indices.
AB  - Bicoherence quantifies the degree of quadratic phase coupling among different
      frequency components within a signal. Previous studies, using Fourier-based
      methods of bicoherence calculation (FBIC), have demonstrated that
      electroencephalographic bicoherence can be related to the end-tidal concentration
      of inhaled anesthetic drugs. However, FBIC methods require excessively long
      sections of the encephalogram. This problem might be overcome by the use of
      wavelet-based methods. In this study, we compare FBIC and a recently developed
      wavelet bicoherence (WBIC) method as a tool to quantify the effect of isoflurane
      on the electroencephalogram. We analyzed a set of previously published
      electroencephalographic data, obtained from 29 patients who underwent elective
      abdominal surgery under isoflurane general anesthesia combined with epidural
      anesthesia. Nine potential indices of the electroencephalographic anesthetic
      effect were obtained from the WBIC and FBIC techniques. The relationship between
      each index and end-tidal concentrations of isoflurane was evaluated using
      correlation coefficients (r), the inter-individual variations (CV) of index
      values, the coefficient of determination (R(2)) of the PKPD models and the
      prediction probability (P(K)). The WBIC-based indices tracked anesthetic effects
      better than the traditional FBIC-based ones. The DiagBic_En index (derived from
      the Shannon entropy of the diagonal bicoherence values) performed best [r = 0.79
      (0.66-0.92), CV = 0.08 (0.05-0.12), R(2) = 0.80 (0.75-0.85), P(K) = 0.79 (0.75
      0.83)]. Short data segments of ~10-30 s were sufficient to reliably calculate the
      indices of WBIC. The wavelet-based bicoherence has advantages over the
      traditional Fourier-based bicoherence in analyzing volatile anesthetic effects on
      the electroencephalogram.

PMID- 21881167
TI  - Cooperative effects of Akt-1 and Raf-1 on the induction of cellular senescence in
      doxorubicin or tamoxifen treated breast cancer cells.
AB  - Escape from cellular senescence induction is a potent mechanism for
      chemoresistance. Cellular senescence can be induced in breast cancer cell lines
      by the removal of estrogen signaling with tamoxifen or by the accumulation of DNA
      damage induced by the chemotherapeutic drug doxorubicin. Long term culturing of
      the hormone-sensitive breast cancer cell line MCF-7 in doxorubicin (MCF-7/DoxR)
      reduced the ability of doxorubicin, but not tamoxifen, to induce senescence. Two
      pathways that are often upregulated in chemo- and hormonal-resistance are the
      PI3K/PTEN/Akt/mTOR and Ras/Raf/MEK/ERK pathways. To determine if active Akt-1 and
      Raf-1 can influence drug-induced senescence, we stably introduced activated
      DeltaAkt-1(CA) and DeltaRaf-1(CA) into drug-sensitive and doxorubicin-resistant
      cells. Expression of a constitutively-active Raf-1 construct resulted in higher
      baseline senescence, indicating these cells possessed the ability to undergo
      oncogene-induced-senescence. Constitutive activation of the Akt pathway
      significantly decreased drug-induced senescence in response to doxorubicin but
      not tamoxifen in MCF-7 cells. However, constitutive Akt-1 activation in drug
      resistant cells containing high levels of active ERK completely escaped cellular
      senescence induced by doxorubicin and tamoxifen. These results indicate that up
      regulation of the Ras/PI3K/PTEN/Akt/mTOR pathway in the presence of elevated
      Ras/Raf/MEK/ERK signaling together can contribute to drug-resistance by
      diminishing cell senescence in response to chemotherapy. Understanding how breast
      cancers containing certain oncogenic mutations escape cell senescence in response
      to chemotherapy and hormonal based therapies may provide insights into the design
      of more effective drug combinations for the treatment of breast cancer.

PMID- 21881173
TI  - (1H-pyrazole-kappaN2)(2,2':6',2''-terpyridine-kappa3N,N',N'')platinum(II)
      bis(perchlorate) nitromethane monosolvate.
AB  - The reaction between [PtCl(terpy)].2H(2)O (terpy is 2,2':6',2''-terpyridine) and
      pyrazole in the presence of two equivalents of AgClO(4) in nitromethane yields
      the title compound, [Pt(C(3)H(4)N(2))(C(15)H(11)N(3))](ClO(4))(2).CH(3)NO(2), as
      a yellow crystalline solid. Single-crystal X-ray diffraction shows that the
      dicationic platinum(II) chelate is square planar with the terpyridine ligand
      occupying three sites and the pyrazole ligand occupying the fourth. The torsion
      angle subtended by the pyrazole ring relative to the terpyridine chelate is 62.4
      (6) degrees . Density functional theory calculations at the LANL2DZ/PBE1PBE level
      of theory show that in vacuo the lowest-energy conformation has the pyrazole
      ligand in an orientation perpendicular to the terpyridine ligand (i.e. 90 degrees
      ). Seemingly, the stability gained by the formation of hydrogen bonds between the
      pyrazole NH group and the perchlorate anion in the solid-state structure is
      sufficient for the chelate to adopt a higher-energy conformation.

PMID- 21881174
TI  - A photochromic dinuclear compound: aquatetrakis(MU-2,3-diphenylprop-2
      enoato)bis(2,3-diphenylprop-2-enoato)ethanolbis(1,10
      phenanthroline)dilanthanum(III).
AB  - The title dinuclear complex, (aqua-1kappaO)tetrakis(MU-2,3-diphenylprop-2-enoato
      1:2kappa(2)O:O')bis(2,3-diphenylprop-2-enoato)-1kappaO;2kappaO-(ethanol
      2kappaO)bis(1,10-phenanthroline)-1kappa(2)N,N';2kappa(2)N,N'-dilanthanum(III),
      [La(2)(C(15)H(11)O(2))(6)(C(12)H(8)N(2))(2)(C(2)H(5)OH)(H(2)O)], contains two
      similar La(III) centres with distorted [LaO(6)N(2)] bicapped triganol-prismatic
      coordination polyhedra formed by six phenylcinnamate (PCA(-) or 2,3-diphenylprop
      2-enoate) ligands, two 1,10-phenanthroline (phen) ligands, a coordinating ethanol
      molecule and a coordinating water molecule. The two metal centres are bridged by
      four MU-PCA(-) ligands, with the remaining two PCA(-) ligands coordinated in a
      monodentate fashion. The noncoordinated carboxylate O atoms on the terminal PCA(
      ) ligands form O-H...O hydrogen bonds with the coordinated solvent molecules.
      Each La centre is also coordinated by a bidentate phen ligand. The PCA(-) ligands
      all adopt syn-syn orientations, with the two phenyl rings presenting dihedral
      angles of about 70 degrees . The compound displays photochromic behaviour both in
      solution and in the solid state.

PMID- 21881175
TI  - Bis(MU-5-carboxybenzene-1,3-dicarboxylato-kappa2O1:O3)bis[(2,2'-bi-1H-imidazole
      kappa2N3,N3')zinc].
AB  - The title compound, [Zn(2)(C(9)H(4)O(6))(2)(C(6)H(6)N(4))(2)], consists of two
      Zn(II) ions, two 5-carboxybenzene-1,3-dicarboxylate (Hbtc(2-)) dianions and two
      2,2'-bi-1H-imidazole (bimz) molecules. The Zn(II) centre is coordinated by two
      carboxylate O atoms from two Hbtc(2-) ligands and by two imidazole N atoms of a
      bimz ligand, in a distorted tetrahedral coordination geometry. Two neighbouring
      Zn(II) ions are bridged by a pair of Hbtc(2-) ligands, forming a discrete
      binuclear [Zn(2)(Hbtc)(2)(bimz)(2)] structure lying across an inversion centre.
      Hydrogen bonds between carboxyl H atoms and carboxylate O atoms and between
      imidazole H atoms and carboxylate O atoms link the binuclear units. These
      binuclear units are further extended into a three-dimensional supramolecular
      structure through extensive O-H...O and N-H...O hydrogen bonds. Moreover, the
      three-dimensional nature of the crystal packing is reinforced by the pi-pi
      stacking. The title compound exhibits photoluminescence in the solid state, with
      an emission maximum at 415 nm.

PMID- 21881176
TI  - Tetrakis(tetramethylammonium) tricarbonatodioxidouranate octahydrate.
AB  - The environment of the U atom in the title compound,
      (C(4)H(12)N)(4)[UO(2)(CO(3))(3)].8H(2)O, presents a typical hexagonal bipyramidal
      geometry found in many actinide complexes. It is a model for actinide species and
      consists of common environmental moieties (carbonate, water and ammonia species).
      The structure displays a sheet-like hydrogen-bonding network formed from
      crystallization water molecules and carbonate ligands. The compound is
      isomorphous with a previously described Np isolog [Grigorev et al. (1997).
      Radiokhimiya (Russ. Radiochem.), 39, 325-329].

PMID- 21881177
TI  - Weak C-H...Cl-Pd interactions toward conformational polymorphism in trans
      dichloridobis(triphenylphosphane)palladium(II).
AB  - A new triclinic polymorph of the title compound, [PdCl(2)(C(18)H(15)P)(2)], has
      two independent molecules in the unit cell, with the Pd atoms located on
      inversion centres. One molecule has an eclipsed conformation, whereas the second
      molecule adopts a gauche conformation. The molecules with a gauche conformation
      are involved in weak intermolecular C-H...Cl-Pd interactions with symmetry
      related molecules. It is suggested that C-H...Cl-Pd interactions are mainly
      responsible for the existence of conformational differences, which contribute to
      the polymorph formation. In the crystal, there are layers of eclipsed and gauche
      molecules separated by normal van der Waals interactions.

PMID- 21881179
TI  - catena-Poly[[silver(I)-MU-1,3-bis(4-pyridyl)propane] hemi(naphthalene-1,5
      disulfonate) dihydrate]: a three-dimensional metallo-supramolecular sandwich
      lamellar network.
AB  - The title compound, {[Ag(C(13)H(14)N(2))](C(10)H(6)O(6)S(2))(0.5).2H(2)O}(n),
      (I), features a three-dimensional supramolecular sandwich architecture that
      consists of two-dimensional cationic layers composed of polymeric chains of
      silver(I) ions and 1,3-bis(4-pyridyl)propane (bpp) ligands, linked by Ag...Ag and
      pi-pi interactions, alternating with anionic layers in which uncoordinated
      naphthalene-1,5-disulfonate (nds(2-)) anions and solvent water molecules form a
      hydrogen-bonded network. The asymmetric unit consists of one Ag(I) cation
      linearly coordinated by N atoms from two bpp ligands, one bpp ligand, one half of
      an nds(2-) anion lying on a centre of inversion and two solvent water molecules.
      The two-dimensional {[Ag(bpp)](+)}(n) cationic and {[(nds).2H(2)O](2-)}(n)
      anionic layers are assembled into a three-dimensional supramolecular framework
      through long secondary coordination Ag...O interactions between the sulfonate O
      atoms and Ag(I) centres and through nonclassical C-H...O hydrogen bonds.

PMID- 21881178
TI  - Two W/Cu/S clusters: tetraethylammonium bromidodi-MU2-sulfido-sulfido[tris(3,5
      dimethylpyrazol-1-yl)borato]copper(I)tungsten(VI) and tetraethylammonium
      dibromido-MU3-sulfido-di-MU2-sulfido-[tris(3,5-dimethylpyrazol-1
      yl)borato]dicopper(I)tungsten(VI).
AB  - The reaction of (Et(4)N)[Tp*WS(3)] [Tp* = hydrogen tris(3,5-dimethylpyrazol-1
      yl)borate] with one or two equivalents of CuBr afforded the [1 + 1] and [1 + 2]
      addition products (Et(4)N)[Tp*WS(MU-S)(2)(CuBr)] {or
      (C(8)H(20)N)[CuWBr(C(15)H(22)BN(6))S(3)], (I)} and (Et(4)N)[Tp*W(MU(3)-S)(MU
      S)(2)(CuBr)(2)] {or (C(8)H(20)N)[Cu(2)WBr(2)(C(15)H(22)BN(6))S(3)], (II)}. The
      anion of (I) contains a [W(MU-S)(2)Cu] core formed by the addition of one CuBr
      unit to the [Tp*WS(3)] species. The anion of (II) has a butterfly-shaped [W(MU(3)
      S)(MU-S)(2)Cu(2)] core formed by the addition of two CuBr units to the [Tp*WS(3)]
      species. The [Tp*WS(3)] sections of each complex exhibit approximate C(3v) point
      symmetry and have closely comparable geometry. In (II), both the anion and cation
      lie on a crystallographic mirror plane. The structure of (I) is
      noncentrosymmetric and polar.

PMID- 21881180
TI  - catena-Poly[[[MU-1,3-bis(diphenylphosphanyl)propane-kappa2P:P'][O-ethyl (4
      methoxyphenyl)phosphonodithioato-kappa2S,S']silver(I)] chloroform monosolvate].
AB  - Reaction of a mixture of AgOAc, Lawesson's reagent [2,4-bis(4-methoxyphenyl)-1,3
      dithiadiphosphetane-2,4-disulfide] and 1,3-bis(diphenylphosphanyl)propane (dppp)
      under ultrasonic treatment gave the title compound,
      {[Ag(C(9)H(12)O(2)PS(2))(C(27)H(26)P(2))].CHCl(3)}(n), a novel one-dimensional
      chain based on the in situ-generated bipodal ligand [ArP(OEt)S(2)](-) (Ar = 4
      methoxyphenyl). The compound consists of bidentate bridging 1,3
      bis(diphenylphosphanyl)propane (dppp) and in situ-generated bidentate chelating
      [ArP(OEt)S(2)](-) ligands. The dppp ligand links the [Ag{ArP(OEt)S(2)}] subunit
      to form an achiral one-dimensional infinite chain. These achiral chains are
      packed into chiral crystals by virtue of van der Waals interactions. No pi-pi
      interactions are observed in the crystal structure.

PMID- 21881181
TI  - A tetranuclear copper(II) cluster: bis(MU-4-chlorobenzoato-kappa2O:O')(4
      chlorobenzoato-kappa2O,O')(4-chlorobenzoato-kappaO)tetrakis(MU3-2
      pyridylmethanolato-kappa4N,O:O:O)tetracopper(II).
AB  - The title compound, [Cu(4)(C(7)H(4)ClO(2))(4)(C(6)H(6)NO)(4)], consists of
      isolated tetranuclear clusters, where the Cu(2+) cations are five- and sixfold
      coordinated by O atoms from the 4-chlorobenzoate anions and by pyridine N and
      methanolate O atoms from bidentate 2-pyridylmethanolate ligands. While three Cu
      atoms are six-coordinated by an NO(5) donor set forming distorted octahedra, the
      fourth Cu atom is five-coordinated by an NO(4) donor set forming a distorted
      tetragonal-pyramidal coordination around the Cu atom. The nucleus is a deformed
      cubane-like Cu(4)O(4) structure, with Cu...Cu distances in the range 3.0266 (11)
      3.5144 (13) A.

PMID- 21881182
TI  - The supramolecular architecture in 4,4'-bipyridinium bis(hydrogen oxalate).
AB  - The asymmetric unit of the title compound, C(10)H(10)N(2)(2+).2C(2)HO(4)(-),
      consists of one half of a 4,4'-bipyridinium cation, which has inversion symmetry,
      and a hydrogen oxalate anion, in which an intramolecular hydrogen bond exists.
      The cations and anions are connected by O-H...O, N-H...O and C-H...O hydrogen
      bonds, forming a two-dimensional network, whereas pi-pi stacking interactions
      involving the 4,4'-bipyridinium cations lead to the formation of a three
      dimensional supramolecular structure. An unusual deca-atomic ring is formed
      between two hydrogen oxalate anions, which are linked side-to-side via O-H...O
      hydrogen-bonding interactions.

PMID- 21881183
TI  - 5:1 and 2:1 cocrystals of 2,3,4,5,6-pentafluorophenol with phenazine.
AB  - 2,3,4,5,6-Pentafluorophenol (pFp), unlike phenol, forms cocrystals with the weak
      heteroaromatic base phenazine (phz). Two types of cocrystals were prepared, (I)
      with a high content of pFp, 2,3,4,5,6-pentafluorophenol-phenazine (5/1),
      5C(6)HF(5)O.C(12)H(8)N(2), and (II) with a 2:1 pFp-phz molar ratio, 2,3,4,5,6
      pentafluorophenol-phenazine (2/1), 2C(6)HF(5)O.C(12)H(8)N(2). In both forms,
      homostacks are formed by the heterocyclic base and phenol molecules and no aryl
      perfluoroaryl stacking interactions occur. The arrangement of the molecules in
      the crystal of (I) is determined by strong O-H...N and O-H...O hydrogen bonds,
      weak O-H...F, C-H...F and C-H...O interactions, pi-pi stacking interactions
      between the phz molecules and C-F...pi(F) interactions within the pFp stacks.
      Among the specific interactions in (II) are a strong O-H...N hydrogen bond, weak
      C-H...F interactions and pi-pi stacking interactions between the phz molecules.
      In (I) and (II), the heterocyclic molecules are located around inversion centres
      and one of the symmetry-independent pFp molecules in (I) is disordered about an
      inversion centre. Remarkably, similar structural fragments consisting of six pFp
      stacks can be identified in cocrystal (I) and in the known orthorhombic polymorph
      of pFp with Z' = 3 [Gdaniec (2007). CrystEngComm, 9, 286-288].

PMID- 21881184
TI  - Tosyl esters of cinchonidine and cinchonine alkaloids: the structure-reactivity
      relationship in the hydrolysis to 9-epibases.
AB  - In the crystal structures of the diastereoisomers of O-tosylcinchonidine [(9R)
      cinchon-9-yl 4-methylbenzenesulfonate], (I), and O-tosylcinchonine [(9S)-cinchon
      9-yl 4-methylbenzenesulfonate], (II), both C(26)H(28)N(2)O(3)S, both molecules
      are in an anti-closed conformation and, in each case, the position of the aryl
      ring of the tosylate system is influenced by an intramolecular C-H...O hydrogen
      bond. The molecular packing in (I) is influenced by weak intermolecular C-H...O
      and C-H...pi interactions. The crystal structure of (II) features C-H...pi
      interactions and van der Waals forces only. The computational investigations
      using RHF/6-31G** ab initio and AM1 semi-empirical methods performed for (I) and
      (II) and their protonated species show that the conformational and energetic
      parameters of the molecules are correlated with differences in their reactivity
      in hydrolysis to the corresponding 9-epibases.

PMID- 21881185
TI  - Little change but great effect: varying supramolecular interactions in 2,5
      dimethoxyterephthalic acid and 2,5-diethoxyterephthalic acid.
AB  - The title terephthalic acid derivatives, namely 2,5-dimethoxyterephthalic acid,
      C(10)H(10)O(6), (I), and 2,5-diethoxyterephthalic acid, C(12)H(14)O(6), (II),
      exhibit nearly planar molecular structures, with maximum deviations from the
      least-squares planes calculated for all non-H atoms of 0.0418 (6) and 0.0902 (10)
      A for (I) and (II), respectively. The molecules of both title compounds contain
      an inversion centre and thus the asymmetric unit of both crystal structures
      consists of only half a molecule. It is a remarkable fact that a comparatively
      small change in the substitution of the terephthalic acid [dimethoxy in (I)
      versus diethoxy in (II)] causes major differences in the dominating
      supramolecular interactions. While in (II) the packing structure is stabilized by
      typical intermolecular hydrogen-bonded carboxylic acid dimer interactions, the
      carboxyl group in (I) forms an unusual intramolecular hydrogen bond with the O
      atom of the neighbouring methoxy group.

PMID- 21881186
TI  - 1,2-Bis[(pyridin-2-ylmethyl)sulfanyl]ethane and its dimorphic hydrochloride salt.
AB  - Although having been described as a liquid in the literature for 41 years, 1,2
      bis[(pyridin-2-ylmethyl)sulfanyl]ethane, C(14)H(16)N(2)S(2), (I), has now been
      obtained as monoclinic crystals via a new and convenient method of purification.
      Molecules of (I) are located on crystallographic inversion centres and are held
      together by C-H...N and C-H...S interactions, resulting in the formation of a
      three-dimensional network structure. In addition, two polymorphs of the
      corresponding hydrochloride salt, 2-[({2-[(pyridin-1-ium-2
      ylmethyl)sulfanyl]ethyl}sulfanyl)methyl]pyridin-1-ium dichloride,
      C(14)H(18)N(2)S(2)(2+).2Cl(-), (II) and (III), have been isolated. Molecules of
      (II) and (III) have similar conformations and are located on inversion centres.
      Both polymorphs form three-dimensional networks through N-H...Cl, C-H...Cl and C
      H...S interactions. The structure of (III) displays voids of 35 A(3).

PMID- 21881187
TI  - N-(tert-butoxycarbonyl)-O-allyl-L-seryl-alpha-aminoisobutyryl-L-valine methyl
      ester: a protected tripeptide with an allylated serine residue.
AB  - The title compound [systematic name (6S,12S)-methyl 6-(allyloxymethyl)-12
      isopropyl-2,2,9,9-tetramethyl-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oate],
      C(21)H(37)N(3)O(7), containing the little studied O-allyl-L-serine residue
      [Ser(All)], crystallizes in the monoclinic space group C2 with one molecule in
      the asymmetric unit. The compound is an analogue of the Ser140-Val142 segment of
      the water channel aquaporin-4 (AQP4). It forms a distorted type-II beta-turn with
      a P(II)-3(10L)-P(II) backbone conformation (P(II) is polyproline II). The overall
      backbone conformation is markedly different from that of the CO(Pro139)-Val142
      stretch of rat AQP4, but is quite similar to the corresponding segment of human
      AQP4, despite significant differences at the level of the individual residues.
      The side chain of the Ser(All) residue adopts a gauche conformation relative to
      the backbone CO-C(alpha) and C(alpha)-N bonds. The H atoms of the two CH(2)
      groups in the Ser(All) side chain are almost eclipsed. The crystal packing of the
      title compound is divided into one-molecule-thick layers, each layer having a
      hydrophilic core and distinct hydrophobic interfaces on either side.

PMID- 21881188
TI  - (E)-4-[2-(3,4,5-trimethoxyphenyl)ethenyl]nitrobenzene and its 'bridge-flipped'
      analogues.
AB  - The solid-state structures of three push-pull acceptor-pi-donor (A-pi-D) systems
      differing only in the nature of the pi-spacer have been determined. (E)-1-Nitro-4
      [2-(3,4,5-trimethoxyphenyl)ethenyl]benzene, C(17)H(17)NO(5), (I), and its 'bridge
      flipped' imine analogues, (E)-3,4,5-trimethoxy-N-(4-nitrobenzylidene)aniline,
      C(16)H(16)N(2)O(5), (II), and (E)-4-nitro-N-(3,4,5-trimethoxybenzylidene)aniline,
      C(16)H(16)N(2)O(5), (III), display different kinds of supramolecular networks,
      viz. corrugated planes, a herringbone pattern and a layered structure,
      respectively, all with zero overall dipole moments. Only (III) crystallizes in a
      noncentrosymmetric space group (P2(1)2(1)2(1)) and is, therefore, a potential
      material for second-harmonic generation (SHG).

PMID- 21881189
TI  - A 1:1 cocrystal of fluconazole with salicylic acid.
AB  - The interaction of the antifungal pharmaceutical agent fluconazole with salicylic
      acid in acetonitrile solution yields the 1:1 cocrystal 2-(2,4-difluorophenyl)-1,3
      bis(1H-1,2,4-triazol-1-yl)propan-2-ol-2-hydroxybenzoic acid (1/1),
      C(13)H(12)F(2)N(6)O.C(7)H(6)O(3). The asymmetric unit consists of one molecule of
      fluconazole and one molecule of salicylic acid, both in their neutral forms. Both
      crystal agents form head-to-tail hydrogen-bonded dimers, which are further
      connected into hydrogen-bonded extended zigzag tapes propagating along the ac
      diagonal.

PMID- 21881190
TI  - [Development and aging of bone in the female life cycle].
AB  - In Japan, where the society is fast aging at an unprecedented pace, osteoporosis
      is estimated to affect more than 15 million individuals, thus representing a
      "common" disease, which exactly meets the definition of a lifestyle-related
      disease. As osteoporosis has a predominantly female prevalence and bone accounts
      for the most marked gender difference all organs commonly affected in males and
      females alike, to have an understanding of the development and aging of bone in
      women represents an urgent task toward gaining a better understanding of the
      pathophysiology of osteoporosis affecting them as well as its clinical stages. In
      this context, the benefit of ensuring bone health has been identified as
      maintenance of ADL/QOL in the elderly as well as prevention of osteoporotic
      fractures which lead to affected individuals becoming bed-ridden and requiring
      nursing care.

PMID- 21881191
TI  - [Development of the skeletal system in utero].
AB  - The skeletal system develops from mesenchyme originated from the mesodermal germ
      layer and neural crest. In view of developmental bone biology, the skeletal
      system can be divided into four parts : skull, limbs, vertebrae/the ventral
      column, and ribs/sternum. Bone formation takes place in two ways. In most bones
      including axial (vertebral column and ribs) and appendicular (limbs) skeletons, a
      cartilage model first forms and is finally replaced with bone, which is called
      endochondral ossification. In contrast, most flat bones, such as the majority of
      bones of the skull, form directly from mesenchymal cells without the prior
      formation of cartilage ; this type of osteogenesis is called intramembranous
      ossification. I here discuss development of the skeletal system focusing on its
      time line in utero.

PMID- 21881192
TI  - [Bone mass accrual during infancy].
AB  - Bone mass during infantile period relates closely to adult bone mass and small
      bone mass in infancy has been thought as one of the risk factors for
      osteoporosis. Although bone mass accrual during infantile period is determined by
      perinatal condition, nutrition and endocrine factors, among these factors, infant
      growth at third trimester of pregnancy is important to determine life-long bone
      health. For nutritional factors, vitamin D and calcium are important. The effects
      of estrogen on infant bone are also discussed.

PMID- 21881193
TI  - [Perimenarchial growth spurt of the bone].
AB  - Peak bone mass negatively predicts the lifetime cumulative incidence of
      osteoporosis and fractures. Osteoporosis is a highly prevalent disease and
      fractures at an advanced age worsen life expectancy. It is therefore important to
      prevent progression of this disease. However, curbing the loss of already
      osteoporotic bone is not an easy task. Adolescence is a critical period for bone
      acquisition. Maximizing peak bone mass during puberty will ultimately guard
      against osteoporosis. In this review, we focus on the hormonal effects of puberty
      on bone growth and the importance of appropriate exercise and nutrition to
      optimize bone accrual.

PMID- 21881194
TI  - [Effect of exercise on developing bone mass and cortical bone geometry].
AB  - Mechanical load which comes mainly from muscle force as well as gravitational
      force associated with body weight plays an important role in increasing bone mass
      and bone strength. The greater is mechanical load to the bone, the larger are the
      increases in bone mass and bone strength. In particular, jumping exercise
      produces a large amount of mechanical forces loaded to the bone through muscle
      force. Jumping exercise together with calcium supplementation during the pre- and
      peri-pubertal periods is reported to be effective in stimulating bone growth and
      thereby increasing bone mineral content. In girls, interventions must be
      initiated during the pre-menarcheal period to effectively maximize peak bone
      mass.

PMID- 21881195
TI  - [Nutrition in bone growth and development].
AB  - The greatest increase in bone density was observed around ages 10-14 years in
      girls and thereafter peak bone mass was attained. Maximizing peak bone mass
      during adolescence is one of the most important strategies to decrease
      osteoporotic fractures later in life. Initial bone mass adjusted by height and
      weight in 10-year-old girl was associated positively with intakes of dairy
      products and small fish. Annual increase in bone mass from age 10 years to 11
      years was associated positively with increased intake of fish, fruit, vegetables,
      and soybeans. Thus, not only calcium but also adequate dietary patterns such as
      increased intake of fish, fruit, vegetables, and soy products lead to higher peak
      bone mass in adolescent and will decrease the risk of bone fracture in
      postmenopausal age.

PMID- 21881196
TI  - [Metabolic changes in bone and calcium in pregnancy and puerperium].
AB  - Calcium transfer from the mother to the fetus and neonate during pregnancy and
      lactation plays an extremely important role in the bone health of the mother and
      infant. Calcium aids in bone health through all ages but is especially crucial
      during pregnancy and lactation. Despite facing similar demands for calcium in
      pregnancy and puerperium, the maternal adaptations differ significantly between
      these two reproductive periods. Although the studies are underway to establish
      the conclusion, the changes in the structure and metabolism of bone and calcium
      during pregnancy and the early stage of postpartum are evaluated by investigating
      bone mineral density (BMD) , bone histomorphometry and bone markers of human or
      animal models. The bone resorption increased at the end of pregnancy and
      lactation, and the bone formation increases and the bone structure is almost
      recovered after cessation of lactating in postpartum. Vitamin D and parathyroid
      hormone-related protein (PTHrP) status especially becomes crucial for optimal
      maternal and fetal outcomes, fetal and neonatal skeletal growth, and maternal
      health in later life.

PMID- 21881197
TI  - [Bone loss in lactating women and post-pregnancy osteoporosis].
AB  - Measurement of the bone mineral density have shown that lactating women had 1 to
      3% decrease in bone mineral density. Post pregnancy osteoporosis is rare
      condition that causes fragile fracture mostly in vertebrae. The bone loss in
      lactating women is caused by calcium loss, decrease in estrogen level, and
      increase in PTHrP (parathyroid hormone related protein) level. Some data have
      shown that extended lactation and amenorrhea had an association with the degree
      of bone loss. Mostly, the bone loss of the lactating women recovers to the
      baseline level, soon after the weaning, and there is no long term effect. Post
      pregnancy osteoporosis should be concerned, when we see a lactating woman with
      fragile fracture of the vertebrae.

PMID- 21881198
TI  - [Bone and calcium metabolism in menopause transition].
AB  - Menopause, or estrogen deficiency, predispose women towards fragility fractures
      resulting from impaired bone strength, as the composite consequence of : (1)
      increased bone resorption caused by proliferation and activation of osteoclasts ;
      (2) dissociation of coupling bone formation with resorption ; (3) deterioration
      of bone quality ; (4) decreased calcium absorption from intestines and resorption
      from renal tubules. The current explanation of each phenomenon is described in
      this article, although the exact mechanisms have not been unanimously defined.

PMID- 21881200
TI  - [Bone and calcium metabolism in patients with rheumatoid arthritis].
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
      production of estrogen drops markedly. Disease activity in patients with RA
      decreases during pregnancy and increases postpartum. 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 beneficial effects of estrogen and raloxifene 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 estrogen in the
      pathogenesis and progression of RA.

PMID- 21881199
TI  - [Bone and calcium metabolism in elderly women].
AB  - Bone mass of elderly women reduces after menopause, but the rate of reduction
      differ individually especially in the elderly, because bone metabolism of the
      elderly is influenced by many factors such as hormones, fractures, drugs, ability
      of exercise and/or nutritional level. Therefore, it is quite difficult to
      determine the normal ranges of the metabolism. As a whole, aging accelerates bone
      turnover slowly with wide range of individual variation. Subnormal renal function
      may effect on the excretion or metabolism of bone markers, such as osteocalcin.
      Urinary markers such as NTX corrected by urinary creatinine may be higher than
      the real level, because of low creatinine production in the elderly. These
      factors may influence on the elevated bone metabolism resulting in the
      discrepancy with morphometric evaluation.

PMID- 21881201
TI  - [Difference in osteoporosis in men and women].
AB  - Burden of osteoporosis in men on our society is increasing with aging in
      population. Prevalence of osteoporosis and incidence of osteoporotic fracture are
      less frequent in men than in women since bone mineral density is higher, bone
      size is greater, and hence the bone is stronger in men than in women. In spite of
      these facts, the number of male patients with osteoporosis was projected to be 3
      million in 2005 and is increasing thereafter. Hip fracture was estimated to occur
      in 33,100 men in 2007 and is increasing as well. Once a man suffers from hip
      fracture, prognosis is worse in men than in women. However, screening methods for
      osteoporosis in men are not established, and this causes delay in diagnosis and
      treatment. Further studies are necessary to answer whether the current young
      adult value of bone density necessary for diagnosis is appropriate, whether
      therapeutic regimens are effective in men, whether the cost for diagnosis and
      treatment is comparable to benefit, whether a valid screening method for
      osteoporosis in men exists, and whether the screening method is cost-effective.

PMID- 21881202
TI  - [Is bone biopsy necessary for the diagnosis of metabolic bone diseases? Necessity
      of bone biopsy].
AB  - Histological analysis of undecalcified bone biopsy specimens is a valuable
      clinical and research tool for studying the etiology, pathogenesis and treatment
      of metabolic bone diseases. In case of osteoporosis, bone biopsy is not usually
      required for the diagnosis ; however, bone histomorphometry may be useful in rare
      cases with unusual skeletal fragility. Bone histomorphometry also provides
      valuable information on the mechanism of action, safety and efficacy of new anti
      osteoporosis drugs. Bone histomorphometry is useful for the diagnosis and the
      assessment of treatment response in rickets/osteomalacia and in CKD-MBD (chronic
      kidney disease-mineral and bone disorders) . In Japan, bone biopsy is often
      performed to establish the diagnosis of Paget's disease of bone, especially to
      differentiate it from metastatic bone disease.

PMID- 21881203
TI  - [Is bone biopsy necessary for the diagnosis of metabolic bone diseases? Non-
      invasive assessment of bone turn over markers could define the cause of metabolic
      bone diseases].
AB  - Recent advances of the measurement of bone turn over markers contribute to non
      invasive assessment of bone-metabolic disorders. We can detect the cause of the
      metabolic disorders with bone turn over markers and hormonal profiles more easily
      than before. Today, we can diagnose and treat metabolic bone diseases without
      invasive procedure such as bone biopsy.

PMID- 21881204
TI  - Protective antiviral antibody responses in a mouse model of influenza virus
      infection require TACI.
AB  - Antiviral Abs, for example those produced in response to influenza virus
      infection, are critical for virus neutralization and defense against secondary
      infection. While the half-life of Abs is short, Ab titers can last a lifetime due
      to a subset of the Ab-secreting cells (ASCs) that is long lived. However, the
      mechanisms governing ASC longevity are poorly understood. Here, we have
      identified a critical role for extrinsic cytokine signals in the survival of
      respiratory tract ASCs in a mouse model of influenza infection. Irradiation of
      mice at various time points after influenza virus infection markedly diminished
      numbers of lung ASCs, suggesting that they are short-lived and require extrinsic
      factors in order to persist. Neutralization of the TNF superfamily cytokines B
      lymphocyte stimulator (BLyS; also known as BAFF) and a proliferation-inducing
      ligand (APRIL) reduced numbers of antiviral ASCs in the lungs and bone marrow,
      whereas ASCs in the spleen and lung-draining lymph node were surprisingly
      unaffected. Mice deficient in transmembrane activator and calcium-modulator and
      cyclophilin ligand interactor (TACI), a receptor for BLyS and APRIL, mounted an
      initial antiviral B cell response similar to that generated in WT mice but failed
      to sustain protective Ab titers in the airways and serum, leading to increased
      susceptibility to secondary viral challenge. These studies highlight the
      importance of TACI signaling for the maintenance of ASCs and protection against
      influenza virus infection.

PMID- 21881205
TI  - A mutation in the immunoproteasome subunit PSMB8 causes autoinflammation and
      lipodystrophy in humans.
AB  - Proteasomes are multisubunit proteases that play a critical role in maintaining
      cellular function through the selective degradation of ubiquitinated proteins.
      When 3 additional beta subunits, expression of which is induced by IFN-gamma, are
      substituted for their constitutively expressed counterparts, the structure is
      converted to an immunoproteasome. However, the underlying roles of
      immunoproteasomes in human diseases are poorly understood. Using exome analysis,
      we found a homozygous missense mutation (G197V) in immunoproteasome subunit, beta
      type 8 (PSMB8), which encodes one of the beta subunits induced by IFN-gamma in
      patients from 2 consanguineous families. Patients bearing this mutation suffered
      from autoinflammatory responses that included recurrent fever and nodular
      erythema together with lipodystrophy. This mutation increased assembly
      intermediates of immunoproteasomes, resulting in decreased proteasome function
      and ubiquitin-coupled protein accumulation in the patient's tissues. In the
      patient's skin and B cells, IL-6 was highly expressed, and there was reduced
      expression of PSMB8. Downregulation of PSMB8 inhibited the differentiation of
      murine and human adipocytes in vitro, and injection of siRNA against Psmb8 in
      mouse skin reduced adipocyte tissue volume. These findings identify PSMB8 as an
      essential component and regulator not only of inflammation, but also of adipocyte
      differentiation, and indicate that immunoproteasomes have pleiotropic functions
      in maintaining the homeostasis of a variety of cell types.

PMID- 21881206
TI  - PGC-1alpha promotes recovery after acute kidney injury during systemic
      inflammation in mice.
AB  - Sepsis-associated acute kidney injury (AKI) is a common and morbid condition that
      is distinguishable from typical ischemic renal injury by its paucity of tubular
      cell death. The mechanisms underlying renal dysfunction in individuals with
      sepsis-associated AKI are therefore less clear. Here we have shown that
      endotoxemia reduces oxygen delivery to the kidney, without changing tissue oxygen
      levels, suggesting reduced oxygen consumption by the kidney cells. Tubular
      mitochondria were swollen, and their function was impaired. Expression profiling
      showed that oxidative phosphorylation genes were selectively suppressed during
      sepsis-associated AKI and reactivated when global function was normalized.
      PPARgamma coactivator-1alpha (PGC-1alpha), a major regulator of mitochondrial
      biogenesis and metabolism, not only followed this pattern but was proportionally
      suppressed with the degree of renal impairment. Furthermore, tubular cells had
      reduced PGC-1alpha expression and oxygen consumption in response to TNF-alpha;
      however, excess PGC-1alpha reversed the latter effect. Both global and tubule
      specific PGC-1alpha-knockout mice had normal basal renal function but suffered
      persistent injury following endotoxemia. Our results demonstrate what we believe
      to be a novel mechanism for sepsis-associated AKI and suggest that PGC-1alpha
      induction may be necessary for recovery from this disorder, identifying a
      potential new target for future therapeutic studies.

PMID- 21881207
TI  - The ALS-associated proteins FUS and TDP-43 function together to affect Drosophila
      locomotion and life span.
AB  - The fatal adult motor neuron disease amyotrophic lateral sclerosis (ALS) shares
      some clinical and pathological overlap with frontotemporal dementia (FTD), an
      early-onset neurodegenerative disorder. The RNA/DNA-binding proteins fused in
      sarcoma (FUS; also known as TLS) and TAR DNA binding protein-43 (TDP-43) have
      recently been shown to be genetically and pathologically associated with familial
      forms of ALS and FTD. It is currently unknown whether perturbation of these
      proteins results in disease through mechanisms that are independent of normal
      protein function or via the pathophysiological disruption of molecular processes
      in which they are both critical. Here, we report that Drosophila mutants in which
      the homolog of FUS is disrupted exhibit decreased adult viability, diminished
      locomotor speed, and reduced life span compared with controls. These phenotypes
      were fully rescued by wild-type human FUS, but not ALS-associated mutant FUS
      proteins. A mutant of the Drosophila homolog of TDP-43 had similar, but more
      severe, deficits. Through cross-rescue analysis, we demonstrated that FUS acted
      together with and downstream of TDP-43 in a common genetic pathway in neurons.
      Furthermore, we found that these proteins associated with each other in an RNA
      dependent complex. Our results establish that FUS and TDP-43 function together in
      vivo and suggest that molecular pathways requiring the combined activities of
      both of these proteins may be disrupted in ALS and FTD.

PMID- 21881208
TI  - T cell killing by tolerogenic dendritic cells protects mice from allergy.
AB  - It is well established that allergy development can be prevented by repeated low
      dose exposure to contact allergens. Exactly which immune mechanisms are
      responsible for this so-called low zone tolerance (LZT) is not clear, although
      CD8+ suppressor T cells are known to have a role. Here, we show that TNF released
      by tolerogenic CD11+CD8+ DCs located in skin-draining lymph nodes is required and
      sufficient for development of tolerance to contact allergens in mice. DC-derived
      TNF protected mice from contact allergy by inducing apoptosis in allergen
      specific effector CD8+ T cells via TNF receptor 2 but did not contribute to the
      generation and function of the regulatory T cells associated with LZT. The TNF
      mediated killing mechanism was induced in an allergen-specific manner. Activation
      of tolerogenic DCs by LZT CD8+ suppressor T cells and enhanced TNF receptor 2
      expression on contact allergen-specific CD8+ effector T cells were required for
      LZT. Our findings may explain how tolerance protects from allergic diseases,
      which could allow for the development of new strategies for allergy prevention.

PMID- 21881209
TI  - Cerebral amyloid-beta proteostasis is regulated by the membrane transport protein
      ABCC1 in mice.
AB  - In Alzheimer disease (AD), the intracerebral accumulation of amyloid-beta (Abeta)
      peptides is a critical yet poorly understood process. Abeta clearance via the
      blood-brain barrier is reduced by approximately 30% in AD patients, but the
      underlying mechanisms remain elusive. ABC transporters have been implicated in
      the regulation of Abeta levels in the brain. Using a mouse model of AD in which
      the animals were further genetically modified to lack specific ABC transporters,
      here we have shown that the transporter ABCC1 has an important role in cerebral
      Abeta clearance and accumulation. Deficiency of ABCC1 substantially increased
      cerebral Abeta levels without altering the expression of most enzymes that would
      favor the production of Abeta from the Abeta precursor protein. In contrast,
      activation of ABCC1 using thiethylperazine (a drug approved by the FDA to relieve
      nausea and vomiting) markedly reduced Abeta load in a mouse model of AD
      expressing ABCC1 but not in such mice lacking ABCC1. Thus, by altering the
      temporal aggregation profile of Abeta, pharmacological activation of ABC
      transporters could impede the neurodegenerative cascade that culminates in the
      dementia of AD.

PMID- 21881210
TI  - Smad4 deficiency in T cells leads to the Th17-associated development of
      premalignant gastroduodenal lesions in mice.
AB  - While there is evidence that specific T cell populations can promote the growth
      of established tumors, instances where T cell activity causes neoplasms to arise
      de novo are infrequent. Here, we employed two conditional mutagenesis systems to
      delete the TGF-beta signaling pathway component Smad4 in T cells and observed the
      spontaneous development of massive polyps within the gastroduodenal regions of
      mice. The epithelial lesions contained increased levels of transcripts encoding
      IL-11, IL-6, TGF-beta, IL-1beta, and TNF-alpha, and lamina propria cells isolated
      from lesions contained abundant IL-17A+CD4+ T cells. Furthermore, we found that
      Smad4 deficiency attenuated TGF-beta-mediated in vitro polarization of FoxP3+CD4+
      T cells, but not IL-17A+CD4+ T cells, suggesting that the epithelial lesions may
      have arisen as a consequence of unchecked Th17 cell activity. Proinflammatory
      cytokine production likely accounted for the raised levels of IL-11, a cytokine
      known to promote gastric epithelial cell survival and hyperplasia. Consistent
      with IL-11 having a pathogenic role in this model, we found evidence of Stat3
      activation in the gastric polyps. Thus, our data indicate that a chronic increase
      in gut Th17 cell activity can be associated with the development of premalignant
      lesions of the gastroduodenal region.

PMID- 21881211
TI  - A sodium channel knockin mutant (NaV1.4-R669H) mouse model of hypokalemic
      periodic paralysis.
AB  - Hypokalemic periodic paralysis (HypoPP) is an ion channelopathy of skeletal
      muscle characterized by attacks of muscle weakness associated with low serum K+.
      HypoPP results from a transient failure of muscle fiber excitability. Mutations
      in the genes encoding a calcium channel (CaV1.1) and a sodium channel (NaV1.4)
      have been identified in HypoPP families. Mutations of NaV1.4 give rise to a
      heterogeneous group of muscle disorders, with gain-of-function defects causing
      myotonia or hyperkalemic periodic paralysis. To address the question of
      specificity for the allele encoding the NaV1.4-R669H variant as a cause of HypoPP
      and to produce a model system in which to characterize functional defects of the
      mutant channel and susceptibility to paralysis, we generated knockin mice
      carrying the ortholog of the gene encoding the NaV1.4-R669H variant (referred to
      herein as R669H mice). Homozygous R669H mice had a robust HypoPP phenotype, with
      transient loss of muscle excitability and weakness in low-K+ challenge,
      insensitivity to high-K+ challenge, dominant inheritance, and absence of
      myotonia. Recovery was sensitive to the Na+/K+-ATPase pump inhibitor ouabain.
      Affected fibers had an anomalous inward current at hyperpolarized potentials,
      consistent with the proposal that a leaky gating pore in R669H channels triggers
      attacks, whereas a reduction in the amplitude of action potentials implies
      additional loss-of-function changes for the mutant NaV1.4 channels.

PMID- 21881213
TI  - Politicizing NIH funding: a bridge to nowhere.
AB  - We live in a time of increased spending, mounting debt, and few remedies for
      balancing the federal budget that have bipartisan support. Unfortunately, one
      recent target for decreased allocations of the federal budget is the NIH; the
      discussion of the awarded grants and the grant funding process has been skewed
      and altered to present medical research in an unfriendly light, and this can have
      very damaging repercussions. Politicizing this process could ultimately challenge
      human health, technology, and economic growth.

PMID- 21881212
TI  - Mice overexpressing BAFF develop a commensal flora-dependent, IgA-associated
      nephropathy.
AB  - B cell activation factor of the TNF family (BAFF) is a potent B cell survival
      factor. BAFF overexpressing transgenic mice (BAFF-Tg mice) exhibit features of
      autoimmune disease, including B cell hyperplasia and hypergammaglobulinemia, and
      develop fatal nephritis with age. However, basal serum IgA levels are also
      elevated, suggesting that the pathology in these mice may be more complex than
      initially appreciated. Consistent with this, we demonstrate here that BAFF-Tg
      mice have mesangial deposits of IgA along with high circulating levels of
      polymeric IgA that is aberrantly glycosylated. Renal disease in BAFF-Tg mice was
      associated with IgA, because serum IgA was highly elevated in nephritic mice and
      BAFF-Tg mice with genetic deletion of IgA exhibited less renal pathology. The
      presence of commensal flora was essential for the elevated serum IgA phenotype,
      and, unexpectedly, commensal bacteria-reactive IgA antibodies were found in the
      blood. These data illustrate how excess B cell survival signaling perturbs the
      normal balance with the microbiota, leading to a breach in the normal mucosal
      peripheral compartmentalization. Such breaches may predispose the nonmucosal
      system to certain immune diseases. Indeed, we found that a subset of patients
      with IgA nephropathy had elevated serum levels of a proliferation inducing ligand
      (APRIL), a cytokine related to BAFF. These parallels between BAFF-Tg mice and
      human IgA nephropathy may provide a new framework to explore connections between
      mucosal environments and renal pathology.

PMID- 21881216
TI  - Translational research in neurodevelopmental disorders: development of etiology
      based animal models. Forward.

PMID- 21881214
TI  - Genetics of kidney failure and the evolving story of APOL1.
AB  - Chronic kidney disease (CKD) results from a wide array of processes that impair
      the kidney's ability to perform its major functions. As many as 20 million
      Americans suffer from CKD and nearly a half million from end-stage renal disease,
      but there are also examples of centenarians with adequate renal function. Family
      based and genome-wide studies suggest that genetic differences substantially
      influence an individual's lifetime risk for kidney disease. One emerging theme is
      that evolution of genes related to host defense against pathogens may limit
      kidney longevity. The identification of these genetic factors will be critical
      for expanding our understanding of renal development and function as well as for
      the design of novel therapeutics for kidney disease.

PMID- 21881217
TI  - Genetic animal models of schizophrenia related with the hypothesis of abnormal
      neurodevelopment.
AB  - Accumulating evidence supports the existence of an overlap in genetic
      susceptibility with schizophrenia. Translation of human genetic mutations into
      animals is one of the most important strategies to study the pathogenesis of
      schizophrenia, identify potential drug targets, and test new medicines for
      antipsychotic treatment. Recent discoveries of susceptibility genes for
      schizophrenia make the possibility to develop newer genetic mouse models based on
      the neurodevelopmental hypotheses of schizophrenia. Although it is not possible
      to mimic all schizophrenic symptoms by these animal models, the genetic mouse
      models based on the neurodevelopmental hypothesis are widely developed to
      reproduce several schizophrenia-like behavioral and biochemical changes in
      humans. In this mini review, we will discuss the neuropathological and behavioral
      manifestations of representative genetic mouse models for schizophrenia,
      associated with the hypothesis of abnormal neurodevelopment.

PMID- 21881218
TI  - Animal model for schizophrenia that reflects gene-environment interactions.
AB  - Schizophrenia is a devastating psychiatric disorder that impairs mental and
      social functioning and affects approximately 1% of the population worldwide.
      Genetic susceptibility factors for schizophrenia have recently been reported,
      some of which are known to play a role in neurodevelopment; these include
      neuregulin-1, dysbindin, and disrupted-in-schizophrenia 1 (DISC1). Moreover,
      epidemiologic studies suggest that environmental insults, such as prenatal
      infection and perinatal complication, are involved in the development of
      schizophrenia. The possible interaction between environment and genetic
      susceptibility factors, especially during neurodevelopment, is proposed as a
      promising disease etiology of schizophrenia. Polyriboinosinic-polyribocytidilic
      acid (polyI : C) is a synthetic analogue of double-stranded RNA that leads to the
      pronounced but time-limited production of pro-inflammatory cytokines. Maternal
      immune activation by polyI : C exposure in rodents is known to precipitate a wide
      spectrum of behavioral, cognitive, and pharmacological abnormalities in adult
      offspring. Recently, we have reported that neonatal injection of polyI : C in
      mice results in schizophrenia-like behavioral alterations in adulthood. In this
      review, we show how gene-environment interactions during neurodevelopment result
      in phenotypic changes in adulthood by injecting polyI : C into transgenic mice
      that express a dominant-negative form of human DISC1 (DN-DISC1). Our findings
      suggest that polyI : C-treated DN-DISC1 mice are a well-validated animal model
      for schizophrenia that reflects gene-environment interactions.

PMID- 21881215
TI  - Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling.
AB  - The successful treatment of certain autoimmune conditions with the humanized anti
      IL-6 receptor (IL-6R) antibody tocilizumab has emphasized the clinical importance
      of cytokines that signal through the beta-receptor subunit glycoprotein 130
      (gp130). In this Review, we explore how gp130 signaling controls disease
      progression and examine why IL-6 has a special role among these cytokines as an
      inflammatory regulator. Attention will be given to the role of the soluble IL-6R,
      and we will provide a perspective into the clinical blockade of IL-6 activity in
      autoimmunity, inflammation, and cancer.

PMID- 21881219
TI  - CD38 gene knockout juvenile mice: a model of oxytocin signal defects in autism.
AB  - Oxytocin (OXT) in the hypothalamus is the biological basis of social recognition,
      trust, and bonding. We showed that CD38, a leukaemia cell marker, plays an
      important role in the hypothalamus in the process of OXT release in adult mice.
      Disruption of Cd38 (Cd38(-/-)) produced impairment of maternal behavior and male
      social recognition in mice, similar to the behavior observed in Oxt and OXT
      receptor (Oxtr) gene knockout (Oxt(-/-) and Oxtr(-/-), respectively) mice.
      Locomotor activity induced by separation from the dam was higher and the number
      of ultrasonic vocalization (USV) calls was lower in Cd38(-/-) than Cd38(+/+)
      pups. These phenotypes seemed to be caused by the high plasma OXT levels during
      development from neonates to 3-week-old juvenile mice. ADP-ribosyl cyclase
      activity was markedly lower in the knockout mice from birth, suggesting that
      weaning for mice is a critical time window of differentiating plasma OXT.
      Contribution by breastfeeding was an important exogenous source for regulating
      plasma OXT before weaning by the presence of OXT in milk and the dam's mammary
      glands. The dissimilarity of Cd38(-/-) infant behaviour to Oxt(-/-) or Oxtr(-/-)
      mice can be explained partly by this exogenous source of OXT. These results
      suggest that secretion of OXT into the brain in a CD38-dependent manner may play
      an important role in the development of social behavior, and mice with OXT
      signalling deficiency, including Cd38(-/-), Oxt(-/-) and Oxtr(-/-) mice are good
      animal models for developmental disorders, such as autism.

PMID- 21881220
TI  - Animal models of attention-deficit/hyperactivity disorder.
AB  - Attention-deficit hyperactivity disorder (AD/HD) is a clinically heterogenous
      disorder including hyperactivity, impulsivity, and inattention. Both
      psychostimulant and non-psychostimulant drugs such as methylphenidate and
      atomoxetine, respectively, to modulate catecholeamine neurotransmission are used
      as current pharmacotherapies for AD/HD. Multiple lines of evidence suggest that
      genetic factors play major roles in the etiology of AD/HD. meta-Analyses and
      pooled data analyses have suggested associations between AD/HD and polymorphisms
      in genes encoding monoamine neurotransmission molecules. There has been
      considerable research on this disorder using genetic, pharmacological, and
      neuroimaging approaches, and several animal models of AD/HD such as spontaneously
      hypertensive rat (SHR), dopamine transporter (DAT) knockout mice, coloboma mutant
      mouse, and Grin1 mutant mouse have been reported. These animal models are
      valuable tools for investigating molecular, cellular, and behavioral mechanisms
      as well as the neural development and circuit mechanisms of AD/HD. Here, we
      review the recent literature on animal models of AD/HD and discuss their
      advantages and limitations.

PMID- 21881222
TI  - Effects of serine palmitoyltransferase inhibitor ISP-I on the stratum corneum of
      intact mouse skin.
AB  - Serine palmitoyltransferase (SPT) is involved in the ceramide synthesis pathway.
      We investigated the effects of ISP-I, a potent inhibitor of SPT, on the stratum
      corneum (SC) of hairless mouse skin. Application of ISP-I for one week resulted
      in a significant decrease in the amount of ceramide, which was associated with a
      decrease in SC hydration. However, there was an increase in the number of SC
      layers and less transepidermal water loss than control. Transmission Electron
      Microscopy observation revealed that the number of desmosome-like structures in
      the layers immediately above the stratum granulosum (SG) was significantly
      increased in ISP-I-treated skin compared to vehicle-treated skin. The activity of
      serine protease-an enzyme associated with the process of desquamation-was lower
      in the SC of ISP-I-treated skin than control. Furthermore,
      immunoelectronmicroscopy revealed that glucosylceramide and corneodesmosin tended
      to remain in corneocytes and were not secreted into the intercellular spaces of
      the SC in the ISP-I-treated skin. These results indicate that the application of
      ISP-I decreases ceramide and skin hydration, while at the same time increases the
      number of SC layers. The accumulation of corneocyte layers may originate from an
      aberrant desquamation process related to the decrease in the serine protease
      activity as well as an alteration in the transport of desquamation-related
      proteases by lamellar bodies.

PMID- 21881221
TI  - Antinociceptive efficacy of verticinone in murine models of inflammatory pain and
      paclitaxel induced neuropathic pain.
AB  - Verticinone, an isosteroidal alkaloid separated from Bulbus Fritillaria (Chinese
      name "Bei-mu"), was evaluated for its analgesic activities in murine models of
      inflammatory and neuropathic pain. It was shown that oral administarion of
      verticinone could significantly inhibit acetic acid-induced writhing response in
      a dose-dependent way, and the writhing inhibition of 3 mg/kg verticinone was
      66.2%, which was approximately higher than that of 200 mg/kg aspirin. In the
      formalin test, a high dose of (3 mg/kg) verticinone could inhibit the nociceptive
      response of both phases, but the lower dose (1.5 mg/kg) could only inhibit the
      second phase response, which suggested that verticinone might exert its analgesic
      effect through both central and peripheral mechanisms. In addition, in formalin
      and acetic acid tests, the spontaneous locomotive activities of the mice treated
      with verticinone were transiently greatly decreased when compared with the
      vehicle group. In the rat model of paclitaxel induced neuropathic pain, in
      contrast to the declined analgesic effect of morphine after repeated
      administration with the same dose, a relatively constant analgesic effect of
      verticinone was observed. These investigations suggested that verticinone could
      exert a good antinociceptive effect on inflammatory pain and cancer-related
      neuropathic pain probably through both peripheral and central mechanisms, and it
      might be partly involved with some sedation effects. Verticinone is expected to
      become a potentially novel sedative-analgesic agent without producing tolerance
      and dependence, but further studies are still urgently needed to elucidate the
      precise mechanisms and activities of it.

PMID- 21881223
TI  - The effects of 2-aminoethoxydiphenyl borate and diphenylboronic anhydride on gap
      junctions composed of Connexin43 in TM4 sertoli cells.
AB  - 2-Aminoethoxydiphenyl borate (2-APB) has recently been demonstrated to inhibit
      gap junction (GJ) channels, whereas the underlying mechanisms are still unknown.
      Using mouse TM4 Sertoli cell which expresses connexin43 (Cx43), we explored the
      effects of 2-APB and its analogues on dye-coupling through junctional channels
      formed by Cx43 and on expression of Cx43. Exposure of the cells to 2-APB (1-50
      uM) and one of its analogues diphenylboronic anhydride (DPBA) (1-30 uM) for 4 h
      leads to a significant decrease in dye coupling of GJ in a concentration
      dependent manner. The inhibitory effects of 2-APB and DPBA are reversible since
      decreased GJ coupling resumes after the two compounds are washed out. The
      disfunction of GJ induced by 2-APB and DPBA is associated with a decrease in
      total amount of Cx43 protein and number of GJs on the cell membrane. 2-APB and
      DPBA do not alter Cx43 phosphorylation state and the level of Cx43 mRNA
      expression. The loss of Cx43 protein is prevented by either lysosomal or
      proteasomal inhibitor, suggesting that the decrease in Cx43 results from a 2-APB
      or DPBA-enhanced degradation of Cx43. The present results indicate that 2-APB and
      DPBA inhibit GJ communication through decreasing Cx43 expression in TM4 cells.

PMID- 21881224
TI  - Angiotensin-converting enzyme and Angiotensin-converting enzyme 2 are involved in
      sinoaortic denervation-induced cardiovascular hypertrophy in rats.
AB  - The balance of angiotensin-converting enzyme (ACE) and angiotensin-converting
      enzyme 2 (ACE2) in high blood pressure variability (BPV) induced cardiovascular
      hypertrophy remains elusive. The aim of the present work was to investigate
      expression and activity of ACE and ACE2 in the heart and aorta of sinoaortic
      denervation (SAD) rats with high BPV and normal BP, and explore the potential
      role of ACE and ACE2 in high BPV-induced cardiovascular damage. Hemodynamics,
      cardiovascular hypertrophy, angiotensin II (Ang II) concentrations, ACE and ACE2
      activity were determined. Cardiac-tissue ACE and ACE2 expression were assayed by
      real-time polymerase chain reaction and Western blot. Compared with sham-operated
      rats, systolic BPV and diastolic BPV increased and baroreflex sensitivity
      decreased significantly in SAD rats. SAD rats presented with obvious
      cardiovascular hypertrophy characterized by increased ratio of left ventricle
      weight to body weight and aortic weight to the length of aorta. There was no
      difference in plasma Ang II concentration between sham-operated and SAD rats. The
      cardiac and aortic ACE expression, aortic ACE2 expression and ACE activity were
      elevated in SAD rats. There was no significant difference in cardiac ACE2
      expressions between sham-operated and SAD rats. The present work demonstrated
      that cardiac and aortic ACE expression, aortic ACE2 expression and ACE activity
      were increased in SAD rats. It is the tissue rather than the circulating renin
      angiotensin system that contributes to high BPV-induced cardiovascular
      hypertrophy.

PMID- 21881225
TI  - Study of the relationship between genetics and geography in determining the
      quality of Astragali Radix.
AB  - Astragali Radix (AR), prepared from the roots of Astragalus membranaceus (FISCH.
      ex LINK) BUNGE or its variey, A. membranaceus (FISCH. ex LINK) BUNGE var.
      mongholicus (BUNGE) HSIAO., is one of the most used and valuable traditional
      Chinese medicines (TCMs). Historically, Hunyuan, Shanxi Province in China is the
      geo-authentic producing area of AR and crude AR from here called "geo-authentic."
      According to tradition, geo-authentic TCMs define both authenticity and quality.
      However, no scientific investigation has ever determined whether the superior
      quality of Hunyuan AR is due to the genetic characteristics or to the local
      environment. In our study, seeds of 30 AR samples representing the two varieties
      from different regions were cultivated in Hunyuan under the same conditions. A
      method, using ultra-performance liquid chromatography coupled with photodiode
      array detector and evaporative light scattering detectors, was developed to
      evaluate the quality through a simultaneous determination of four major
      isoflavonoids and four major saponins. The two AR varieties were successfully
      distinguished by principal component analysis while samples of the same species
      with different seeds origins could not be distinguished. A genetic study
      demonstrated that the internal transcribed spacer sequences of the nuclear
      ribosomal DNA in A. membranaceus var. mongholicus samples from different
      geographical regions were highly conservative. These results indicate that the
      content of active components in AR depends on the interaction of genotype and
      environment. At the varietal level, genetic properties appear to be more
      important for pharmaceutical quality than environmental factors, while on the
      intraspecific level environmental factors might be more important than genetic
      properties.

PMID- 21881226
TI  - Executive functions of postweaning protein malnutrition in mice.
AB  - It is well known that nutritional status during the fetal and/or lactation period
      is important for the development of the central nervous system (CNS). In
      contrast, the effect of malnutrition on postweaning development has not yet been
      thoroughly investigated. In the present study, we analyzed the behavioral and
      neuroanatomical effects of protein malnutrition (PM) postweaning in mice.
      Starting at 20-21 d of age, male ddY mice were maintained on a 5% casein diet (PM
      group) or 20% casein diet (control group) for 20 d. On the 20th d, body and brain
      weights of PM mice were lower than those of the control group. PM mice exhibited
      excessive alertness and spontaneous activity under novel conditions in the Irwin
      test. In addition, PM mice showed increased open arm exploration in the elevated
      plus maze compared to control mice. These results suggest that hyperactivity and
      reduced anxiety behavior or higher impulsiveness in PM mice could be due to an
      immature brain.

PMID- 21881227
TI  - Effect of 5-fluorouracil treatment on SN-38 absorption from intestine in rats.
AB  - 5-Fluorouracil (5-FU)-based chemotherapies with irinotecan have been applied for
      the treatment of cancers, and a common dose-limiting toxicity is neutropenia and
      diarrhea. In this study, we investigated the effect of 5-FU treatment on
      expression levels of drug transporters for SN-38 transportation and SN-38
      absorption from the intestine following 5-FU treatment. Expression levels of
      several drug transporters and nuclear receptors in rats after 5-FU treatment were
      evaluated. SN-38 absorption from the intestine was evaluated by SN-38
      concentration levels in serum following SN-38 injection into the intestine of 5
      FU treated rats. The levels of renal multidrug resistance protein 2 (Mrp2) on day
      4 after treatment (400 mg/kg) showed significant upregulation, 359.2 +/- 33.2%
      (mean +/- S.E.) of control. Mrp2 levels in the intestine were downregulated to
      26.2 +/- 8.4% of control. 5-FU treatment (400 mg/kg) also significantly
      downregurated expression levels of P-glycoprotein (P-gp) and breast cancer
      resistance protein (Bcrp) to 41.2 +/- 14.7%, 15.7 +/- 4.3% of control,
      respectively. To evaluate SN-38 absorption from the intestine, SN-38 was loaded
      in to the intestine on day 4 after 5-FU treatment. Pretreatment with 5-FU
      significantly increased SN-38 concentration in the blood 30, 60 and 90 min after
      SN-38 administration. The area under the curve for SN-38 in the 5-FU group was
      significantly higher than in vehicle groups. 5-FU treatment decreased expression
      levels of P-glycoprotein and Bcrp in intestine. The present study suggests that
      combination chemotherapy of 5-FU with irinotecan (CPT-11) may elevate SN-38
      absorption from intestine.

PMID- 21881228
TI  - Fibrinolytic activation promoted by the cyclopentapeptide malformin: involvement
      of cytoskeletal reorganization.
AB  - Malformin A1, a cyclopentapeptide of fungal origin, enhances cellular
      fibrinolytic activity depending on the existence of a cofactor in blood plasma.
      However, the nature of this cofactor remains unknown. Here, we report that
      vitronectin acts as a plasma cofactor of malformin A1. We purified the cofactor
      from bovine plasma by activity-based fractionation, and confirmed that
      vitronectin in conjunction with plasminogen supports the activity of malformin A1
      to promote the fibrinolytic activity of U937 cells. Malformin A1 action was
      abolished by Arg-Gly-Asp peptide (a competitor of vitronectin-integrin binding),
      wortmannin (an inhibitor of signaling kinases), and cytochalasin B (an inhibitor
      of actin polymerization). Changes in actin organization and a decrease in
      filopodia were observed in cells treated with malformin A1 and plasma. A focal
      localization of plasminogen on the cell surface was augmented by malformin A1,
      whereas the amount of cell-surface-bound plasminogen was minimally altered by the
      treatment. Our results suggest the involvement of cytoskeletal reorganization via
      vitronectin signaling in the cellular fibrinolytic activity-enhancing action of
      malformin A1.

PMID- 21881229
TI  - Emodin inhibits proinflammatory responses and inactivates histone deacetylase 1
      in hypoxic rheumatoid synoviocytes.
AB  - Chronic inflammation of rheumatoid arthritis (RA) is promoted by proinflammatory
      cytokines and closely linked to angiogenesis. In the present study, we
      investigated the anti-inflammatory effects of emodin (1,3,8-trihydroxy-6-methyl
      anthraquinone) isolated from the root of Rheum palmatum L. in interleukin 1 beta
      (IL-1beta) and lipopolysaccharide (LPS)-stimulated RA synoviocytes under hypoxia.
      Emodin significantly inhibited IL-1beta and LPS-stimulated proliferation of RA
      synoviocytes in a dose-dependent manner under hypoxic condition. Also, enzyme
      linked immunosorbent assay (ELISA) revealed that emodin significantly reduced the
      production of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF
      alpha), IL-6 and IL-8], mediators [prostagladin E(2) (PGE(2)), matrix
      metalloproteinase (MMP)-1 and MMP-13] and vascular endothelial growth factor
      (VEGF) as an angiogenesis biomarker in IL-1beta and LPS-treated synoviocytes
      under hypoxia. Consistently, emodin attenuated the expression of cyclooxygenase 2
      (COX-2), VEGF, hypoxia inducible factor 1 alpha (HIF-1alpha), MMP-1 and MMP-13 at
      mRNA level in IL-1beta and LPS-treated synoviocytes under hypoxia. Furthermore,
      emodin reduced histone deacetylase (HDAC) activity as well as suppressed the
      expression of HDAC1, but not HDAC2 in IL-1beta and LPS-treated synoviocytes under
      hypoxia. Overall, these findings suggest that emodin inhibits proinflammatory
      cytokines and VEGF productions, and HDAC1 activity in hypoxic RA synoviocytes.

PMID- 21881230
TI  - The influence of glycyrrhiza and antibiotics on the purgative action of sennoside
      a from Daiokanzoto in mice.
AB  - Daiokanzoto (DKT), a Kampo medicine that includes the combination of two crude
      drugs (rhubarb and glycyrrhiza), is clinically effective for constipation. The
      aim of this study is to clarify the influence of glycyrrhiza, three glycyrrhiza
      constituents (glycyrrhizin, liquiritin, and liquiritin apioside), and eight
      antibiotics on the purgative action of DKT, rhubarb, or sennoside A, a
      constituent of rhubarb, in mice. The purgative actions of rhubarb and sennoside A
      were significantly intensified when glycyrrhiza was co-administered orally to
      mice. Liquiritin and liquiritin apioside but not glycyrrhizin showed significant
      amplification of the purgative action in a dose-dependent manner. The purgative
      actions of DKT and sennoside A were significantly reduced by the pre
      administration of ampicillin, cefcapene pivoxil, faropenem, fosfomycin, or
      kanamycin, but were not affected by the pre-administration of clarithromycin or
      levofloxacin. On the other hand, the purgative action of sennoside A was
      significantly reduced by the pre-administration of minocycline, whereas that of
      DKT was not affected. The effect of minocycline on the purgative action of
      sennoside A was lost when glycyrrhiza was co-administered. These results suggest
      that liquiritin and liquiritin apioside contribute as active substances for the
      purgative action of DKT, and some antibiotics reduce the purgative action of DKT
      and sennoside A. Furthermore, glycyrrhiza has the ability to recover the
      purgative action of sennoside A suppressed by minocycline via an unknown
      mechanism.

PMID- 21881231
TI  - Extracellular-superoxide dismutase expression in COS7 cells exposed to cadmium
      chloride.
AB  - Cadmium (Cd), an industrial and environmental pollutant, preferentially
      accumulates in the kidney, a major target for Cd-related toxicity. It has been
      reported that Cd exposure produces reactive oxygen species (ROS) and induces
      cytotoxicity. Extracellular-superoxide dismutase (EC-SOD) is an antioxidant
      enzyme that protects the cells from damaging effects of ROS; however, the effect
      of Cd on the expression of EC-SOD in COS7 cells remains unclear. In this study,
      exposure to cadmium chloride (CdCl2) enhanced intracellular ROS generation and
      induced COS7 cell death. Moreover, exposure to Cd decreased the expression of EC
      SOD at mRNA and protein levels, but not of other SOD isozymes, copper-and zinc
      containing SOD and manganese-containing SOD. The reduction of EC-SOD and cell
      viability was partially attenuated by pretreatment with an antioxidant, N
      acetylcysteine. Further, we determined the involvement of p38-mitogen-activated
      protein kinase (p38-MAPK) in the reduction of EC-SOD. From these observations,
      p38-MAPK signaling cascades activated by ROS play a pivotal role in the reduction
      of EC-SOD, and it is concluded that the reduction of EC-SOD leads to a decrease
      in the resistance to oxidative stress of Cd-exposed COS7 cells.

PMID- 21881232
TI  - Protective effect of soy isoflavone genistein on ischemia-reperfusion in the rat
      small intestine.
AB  - Ischemia-reperfusion (I/R) injury of the intestine is an important factor
      associated with high rates of morbidity and mortality. Intestinal I/R is a common
      clinical problem in the settings of severe burns, circulatory shock and
      strangulation ileus. Intestinal I/R damages remote organs and promotes multi
      organ failure. It has been shown that enteral feeding before ischemic insults is
      beneficial for reducing organ injury and improving survival after intestinal I/R.
      In that study, the authors used a standard complex enteral diet and they
      suggested that it is important to find new nutrient formulas. Since reactive
      oxygen species are responsible for intestinal I/R injury, we focused on a dietary
      polyphenol, the soy isoflavone genistein. Genistein has a wide spectrum of
      biochemical and pharmacological activities. However, the possibility of a
      protective effect of genistein as enteral nutrition on I/R injury has not been
      investigated. We therefore investigated the protective effect of genistein on
      oxidative injury using intestinal I/R model rats. We found that genistein, which
      has combined antioxidant activity from radical scavenging, xanthine oxidase
      inhibition and chain-breaking effects, exhibits a protective effect on intestinal
      I/R injury. The results suggest that genistein, a soy isoflavone, has the
      possibility as a new nutrient formula of enteral feeding.

PMID- 21881233
TI  - beta-Citryl-L-glutamate acts as an iron carrier to activate aconitase activity.
AB  - The compound beta-citryl-L-glutamate (beta-CG) was initially isolated from
      developing brains, though its functional roles remain unclear. In in vitro
      experiments, the [Fe(II)(beta-CG)] complex activated aconitase in the presence of
      reducing reagents, whereas no Fe complex with citrate, glutamate, or deferoxamine
      displayed such an effect. beta-CG and [Fe(II)(beta-CG)] both bound to the fourth
      labile Fe atom (Fe(a)) in the [4Fe-4S] cluster of aconitase. Furthermore,
      [Fe(II)(beta-CG)] reactivated aconitase damaged by ammonium peroxodisulfate
      (APS), while beta-CG and citrate had no effect. These findings suggest that
      [Fe(II)(beta-CG)] can transfer Fe to aconitase disassembled by APS. In intact
      mitochondria, both beta-CG and [Fe(II)(beta-CG)] bound to Fe(a) of aconitase,
      whereas only [Fe(II)(beta-CG)] reactivated the enzyme disassembled by APS. In
      cultured neuronal cells, beta-CG significantly enhanced cell viability by
      accelerating mitochondrial activity in primary cultures of neurons from newborn
      mouse cerebrum tissues. Thus, the beta-CG plays a role as an Fe-carrier for
      mitochondrial aconitase, and then activates it. Taken together, these findings
      suggest that beta-CG is an endogenous low molecular weight Fe chaperone for
      aconitase.

PMID- 21881234
TI  - Correction of frameshift mutations with tailed duplex DNAs.
AB  - Tailed duplex (TD) DNAs, prepared by annealing an oligonucleotide to a several
      hundred-base single-stranded (ss) DNA fragment, correct a base-substitution
      mutation with high efficiency. In the present study, the abilities of TD
      fragments to correct single-base insertion and deletion mutations were examined,
      using hygromycin-resistance and enhanced green fluorescent protein fusion (Hyg
      EGFP) genes inactivated by +G and -C frameshift mutations. The 5'-TD and 3'-TD
      DNA fragments were co-transfected with plasmid DNA containing the inactivated Hyg
      EGFP gene into CHO-K1 cells, and the gene correction efficiencies were determined
      by introducing the plasmid DNA recovered from the transfected cells into
      Escherichia coli cells. In contrast to their efficiencies for the substitution
      mutation, the gene correction abilities of the TD fragments were relatively low.
      The correction efficiencies by the TD fragments were apparently higher than that
      by a ss DNA fragment, one of the DNA fragments employed for gene correction.
      These results suggest that the TD fragments have the potential to correct
      frameshift mutations, although further improvement is required.

PMID- 21881235
TI  - Characterization of enterococcus strains contained in probiotic products.
AB  - Probiotics are additives containing live microbes that beneficially affect a host
      by improving the properties of the host intestinal microflora. Recently, advances
      in medical treatments have led to increased numbers of immunocompromised
      patients; some patients contract opportunistic infections of Enterococcus
      species, which are considered non-pathogenic bacteria. To evaluate the safety of
      probiotics containing Enterococcus strains, we isolated Enterococcus from six
      probiotic products and compared the pathogenic genes and antimicrobial
      susceptibility of the probiotic strains to those of clinical isolates. Our study
      showed that all Enterococcus strains contained in probiotic products were E.
      faecium, and no vancomycin-resistant strains were found. In addition, no
      pathogenic genes, such as ace, agg, gelE, cylM, cylB, cylA, cpd, cob, ccf,
      efaA(fs), efaA(fm), esp(fs), or esp(fm), were found in the probiotic strains.
      Pulsed-field gel electrophoresis (PFGE) analysis showed obvious genetic
      differences between the probiotic strains and the clinical isolates. The data
      suggested that the probiotic Enterococcus strains were not transmitted to
      hospitalized patients. Therefore, our results strongly suggest that probiotic
      products are unlikely agents for causing opportunistic infections.

PMID- 21881236
TI  - Novel effects of extracts from poisonous mushrooms on expression and function of
      the human ether-a-go-go-related gene channel.
AB  - The human ether-a-go-go-related gene (hERG) encodes the alpha subunit of the
      potassium current I(Kr), which plays a pivotal role in cardiac action potential
      repolarization. Inherited mutations of this gene cause Long QT syndrome type 2.
      hERG expression is altered by several types of drugs as well as by temperature.
      Heat shock protein 70 (Hsp70) and Heat shock cognate protein 70 (Hsc70) have
      reciprocal effects on hERG proteins. We examined the effects of poisonous
      mushrooms on hERG protein expression and its channel function. METHODS: We
      evaluated the effects of several types of poisonous mushrooms on the expression
      and function of wild-type hERG by Western blotting, reverse transcription
      polymerase chain reaction (PCR), and patch clamping in transfected HEK293 cells
      and mouse HL-1 cardiomyocytes. RESULTS: Extracts of Gymnopilus junonius
      (junonius) increased expression of both hERG and Hsp70 in HEK293 cells with
      concomitant decrease in Hsc70, whereas extracts of Amanita ibotengutake
      (ibotengutake) decreased hERG proteins with increase in Hsc70. Knockdown of Hsp70
      and Hsc70 by small interfering RNA abolished the effects of the two mushrooms on
      hERG, respectively. Certain fractions of junonius increased expression of hERG
      proteins. hERG currents were increased by extracts of junonius, resulting in
      shortening of action potential duration (APD). In contrast, hERG currents were
      decreased and APD was prolonged by extracts of ibotengutake. CONCLUSION: junonius
      enhanced the expression and function of hERG by increasing Hsp70 and decreasing
      Hsc70. Ibotengutake decreased hERG expression via increase in Hsc70. Constituents
      of junonius may have the potential for use in treatment of arrhythmia.

PMID- 21881237
TI  - Luteolin shows an antidepressant-like effect via suppressing endoplasmic
      reticulum stress.
AB  - Depression is a significant public health problem and some reports indicate an
      association between depression and endoplasmic reticulum stress. Luteolin is a
      flavonoid contained in many plants and with a variety of known pharmacological
      properties such as anti-inflammatory, anti-anxiety, and memory-improving effects,
      suggesting that luteolin penetrates into the brain. In the present study, we
      investigated the effects of luteolin on endoplasmic reticulum stress-induced
      neuronal cell death. Luteolin significantly suppressed tunicamycin-induced cell
      death at 1 to 10 uM in human neuroblastoma cells. Luteolin increased in the
      expression of the 78 kDa glucose-regulated protein and 94 kDa glucose-regulated
      protein and decreased in the cleavage activation of caspase-3. Additionally, to
      investigate whether chronic luteolin treatment has an antidepression effect, we
      performed some behavioral tests. Chronic luteolin treatment showed antidepressant
      like effects in behavioral tests and, luteolin attenuated the expression of
      endoplasmic reticulum stress-related proteins in the hippocampus of
      corticosterone-treated depression model mice. These findings indicate that
      luteolin has antidepressant-like effects, partly due to the suppression of
      endoplasmic reticulum stress.

PMID- 21881238
TI  - Pharmacodynamic characterization of nitric oxide-mediated vasodilatory activity
      in isolated perfused rat mesenteric artery bed.
AB  - Vasodilation profiles following a short-term infusion of nitric oxide (NO),
      acetylcholine (ACh), and sodium nitroprusside (SNP) into an isolated perfused
      mesenteric artery bed were analyzed in rats to examine their vasodilatory
      efficacy under physiological conditions. These compounds commonly increase the
      intracellular NO concentration to exert vasodilatory activity. In an experiment
      with exogenous NO infusion where 100 ul of 1 : 300 diluted NO-saturated solution
      (approx. 53 pmol of NO) was applied, the infusion caused transient vasodilation
      in a dose-dependent manner, with the peak vasodilation value being 74.7% of the
      maximum relaxation value. In experiments with ACh, the peak vasodilation value
      was 81.5% of the maximum at a dose of 60 pmol. The vasodilation profile of ACh
      was similar to that of NO infusion, but the ACh-induced vasodilation reduced at a
      slower rate than that induced by NO infusion. The vasodilatory activity of SNP
      was less potent than that of ACh, and its peak value was 62.8% of the maximum at
      a dose of 2000 pmol. However, SNP activity was augmented by removing the vascular
      endothelia of the mesenteric artery bed, and the peak value reached 67.3% of the
      maximum at a dose of 60 pmol. Pharmacodynamic analysis indicated that NO and ACh
      are equivalent regarding their vasodilatory efficacy, while the efficacy of SNP
      was less than 1% of theirs, as the arterial vascular endothelium impeded
      intracellular SNP-related NO generation, by which 95% of SNP's vasodilatory
      efficacy was negated. These findings will be helpful to understand factors
      influencing the therapeutic efficacy of vasodilators.

PMID- 21881240
TI  - Endothelial nitric oxide-dependent vasorelaxant effect of isotirumalin, a
      dihydroflavonol from Derris urucu, on the rat aorta.
AB  - The present work aimed to investigate the vasorelaxant effect of isotirumalin, a
      dihydroflavonol isolated from Derris urucu (Leguminosae). The vasorelaxant effect
      of isotirumalin was investigated in the rat aorta, in the presence and in the
      absence of a functional endothelium. The production of nitric oxide (NO) induced
      by isotirumalin was measured simultaneously with its vasorelaxation using carbon
      microsensors. In endothelium-intact aortic rings, isotirumalin induced a
      concentration-dependent vasodilator effect the concentration required to produce
      30% of relaxation (pIC30=4.84+/-0.24) that was abolished in endothelium-denuded
      aortic rings or in the presence of Nomega-nitro-L-arginine-methyl-ester (L-NAME;
      300 uM). In addition, isotirumalin (100 uM) induced a simultaneous and
      significant increase on NO production, which was blunted in the presence of L
      NAME. The present results demonstrate that isotirumalin is a vasodilator in the
      rat aorta and act by a mechanism dependent on the presence of a functional
      endothelium and on NO production.

PMID- 21881239
TI  - Diosgenin from Dioscorea nipponica ameliorates diabetic neuropathy by inducing
      nerve growth factor.
AB  - Diabetic neuropathy is characterized by axonal degeneration, demyelination, and
      atrophy in association with failed axonal regeneration, remyelination, and
      synaptogenesis. Recent reports suggest that reduced levels of nerve growth factor
      (NGF) may play a significant role in the pathogenesis of diabetic polyneuropathy.
      In this study, we investigated the regulation of NGF by steroid diosgenin (DG) in
      a diabetic neuropathy rodent model. We found that DG, the primary spirostane-type
      steroid in several Dioscorea species, increased NGF levels in the sciatic nerve
      of diabetic rats. Additionally, DG increased neurite outgrowth in PC12 cells and
      enhanced nerve conduction velocities in the diabetic neuropathy mouse model. DG
      treated diabetic mice showed reduced disarrangement of the myelin sheath and
      increased area of myelinated axons by electron microscope studies and exhibited
      improvement in the damaged axons. Our data further suggest that DG increased the
      nerve conduction velocity through induction of NGF. Thus, our findings indicate
      that DG, a major sapogenin obtained from Dioscorea nipponica, reverses functional
      and ultrastructural changes and induces neural regeneration in a diabetic
      neuropathy model.

PMID- 21881241
TI  - cis-Ampelopsin E, a stilbene isolated from the seeds of Paeonia suffruticosa,
      inhibits lipopolysaccharide-stimulated nitric oxide production in RAW 264.7
      macrophages via blockade of nuclear factor-kappa B signaling pathway.
AB  - Stilbenes are a class of compounds that has been reported to inhibit a variety of
      pathological processes during inflammatory reactions. In this study, cis
      ampelopsin E, a stilbene isolated from the seeds of Paeonia suffruticosa, was
      shown to dose-dependently reduce the nitric oxide (NO) production from
      lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The reduction in the nitric
      oxide release occurred in parallel with the comparable inhibition of inducible
      nitric oxide synthase (iNOS) enzyme expression, which was achieved by cis
      ampelopsin E's suppressive effect on nuclear factor-kappa B (NF-kappaB) signaling
      activation. By inhibiting LPS-induced inhibitor kinase (IKKalpha/beta)
      phosphorylation, cis-ampelopsin E significantly decreased LPS-induced
      IkappaBalpha phosphorylation, prevented IkappaBalpha degradation, and
      subsequently reduced the translocating of transcription factor p65 into the
      nucleus. As a result, the LPS-induced upregulation of NF-kappaB transcriptional
      activity was efficiently inhibited. Moreover, it is revealed that cis-ampelopsin
      E inhibited LPS-induced cyclooxygenase-2 (Cox-2) expression, cPLA2 activation and
      prostaglandin E2 (PGE2) production. These results, taken together, suggested that
      cis-ampelopsin E might exert potential anti-inflammatory effects via blockage of
      the NF-kappaB signaling pathway.

PMID- 21881242
TI  - The ameliorative effect of 23-hydroxytormentic acid isolated from Rubus coreanus
      on cisplatin-induced nephrotoxicity in rats.
AB  - Previously, the authors demonstrated that the triterpenoid glycoside niga
      ichigoside F1 (NIF1) and its aglycone 23-hydroxytormentic acid (23-HTA) isolated
      from the unripe fruits of Rubus coreanus (Rosaceae) ameliorate cisplatin-induced
      toxicity in renal epithelial LLC-PK1 cells. In the present study, the
      nephroprotective effects of NIF1 and 23-HTA were investigated in Sprague-Dawley
      rats with acute renal injury induced by a single intraperitoneal (i.p.) injection
      of cisplatin (7 mg/kg). Pretreatment with 23-HTA (10 mg/kg/d, per os (p.o.))
      significantly reduced cisplatin-induced elevations in blood urea nitrogen (BUN)
      and serum creatinine level, whereas NIF1 (10 mg/kg, p.o.) slightly reduced these
      levels. In addition, pretreatment with 23-HTA prevented cisplatin-induced
      hydroxyl radical generation, malondialdehyde (MDA) production, glutathione (GSH)
      depletion, and cisplatin-induced changes in the activities of oxidant and
      antioxidant enzymes in rat renal tissues. In addition, histopathological
      examinations showed that 23-HTA pretreatment reduced cisplatin-induced acute
      tubular necrosis and histological changes. In contrast, NIF1 was found to have a
      slight or no influence on cisplatin-induced oxidative enzymes and acute tubular
      necrosis. Taken together, these results suggest that protective effect of 23-HTA
      pretreatment on cisplatin-induced renal damage is associated with the attenuation
      of oxidative stress and the preservation of antioxidant enzymes.

PMID- 21881243
TI  - Rubbing gastric serosal surface enhances naked plasmid DNA transfer in rats and
      mice.
AB  - We have developed in vivo gene transfer to mesothelial cells on the peritoneal
      organs, including the stomach. Simple instillation of naked plasmid DNA onto the
      gastric serosal surface in mice resulted in effective but transient transgene
      expression. Here, we developed a simple method to improve not only the
      transfection efficiency but also the duration of transgene expression. Rubbing
      the gastric serosal surface using a medical spoon immediately after instillation
      of naked plasmid DNA onto the gastric serosal surface resulted in 59-fold higher
      transgene expression 24 h after administration in rats. Without rubbing,
      transgene expression decreased under the detection limit 7 d after
      administration. On the other hand, rubbing the gastric serosal surface with a
      medical spoon after instillation of plasmid DNA prolonged transgene expression
      for one month. Mechanistic study in mice revealed that improved transfection
      should not be due to stimulation of cell function such as macropinocytosis by
      rubbing because rubbing before instillation of plasmid DNA did not improve
      transfection. Plasmid DNA should enter effectively into cells during rubbing.
      These findings are valuable to develop an effective method of in vivo gene
      transfer into peritoneal organs.

PMID- 21881244
TI  - Change in blood kinin and plasma porcine pancreatic kallikrein concentrations
      after oral administration of kallikrein formulation in dog.
AB  - Oral formulation of tissue kallikrein consists primarily of porcine pancreatic
      kallikrein (PPK) and is used to improve peripheral circulation, menopausal
      symptoms, and impaired chorioretinal circulation. Although gastrointestinal
      absorption of tissue kallikrein after oral administration has been reported in
      nonclinical and clinical studies, the increase in the concentration of
      pharmacologically active kinins, which are produced from kininogens by tissue
      kallikrein, has not been investigated. In this study, kallikrein formulation was
      orally administered to dogs and an increase in PPK in plasma was confirmed, along
      with an increase in the blood kinin level. After oral administration of
      kallikrein formulation (10 U/kg or 20 U/kg PPK) to dogs, PPK concentration in
      plasma reached maximum 3 h after administration, and then decreased time
      dependently. The maximum concentration was 6.01 +/- 1.44 pg/ml in the 10 U/kg
      group and 10.88 +/- 3.59 pg/ml in the 20 U/kg group (mean +/- S.E.M, n = 5).
      After oral administration of kallikrein formulation (40 U/kg PPK) to dogs, the
      blood kinin concentration in the PPK-treated group was significantly increased 2
      h after administration as compared to the purified water-treated group (before
      administration: 48.8 +/- 2.1 ng/ml vs. 48.1 +/- 1.9 ng/ml, 2 h after
      administration: 55.5 +/- 1.6 ng/ml vs. 49.6 +/- 1.4 ng/ml; mean +/- S.E.M, n = 4,
      p < 0.05). In conclusion, PPK was considered to be absorbed after oral
      administration and to exert its pharmacological action via kinins produced by
      kininogen degradation in dogs.

PMID- 21881245
TI  - Recent advances in adult congenital heart disease.
AB  - As a result of major achievements in pediatric cardiac care, a growing number of
      patients with congenital heart disease (CHD) are flourishing well into adulthood.
      This heterogeneous and aging population of patients, many of whom represent the
      first generation of middle-age survivors, faces unique issues and challenges. As
      a field, adult CHD has evolved markedly during the past decade on several fronts,
      including imaging, arrhythmia management, percutaneous interventions, surgical
      techniques, research, and multidisciplinary care that extends beyond the cardiac
      realm. This review highlights recent advances across the wide spectrum of key
      issues encountered by adults with CHD.

PMID- 21881246
TI  - Right atrial late gadolinium enhancement on cardiac magnetic resonance imaging in
      pulmonary hypertension.

PMID- 21881247
TI  - Prevalence and correlates of physiological valvular regurgitation in healthy
      subjects.
AB  - BACKGROUND: Although echo Doppler machines have consistently advanced within a
      quarter of a century, age related prevalence of valvular regurgitation detected
      by currently available echo machines remains uncertain. The aim of this study was
      to investigate the prevalence and correlates of valvular regurgitation in healthy
      individuals. METHODS AND RESULTS: A total of 1,333 apparently healthy individuals
      were enrolled in this study. Echocardiographic examinations were performed using
      a currently available echo machine. Aortic regurgitation (AR) was detected less
      frequently (<10%) in younger subjects. Prevalence of aortic regurgitation
      increased with advancing age and reached 46% in their 9th decade. Mitral
      regurgitation (MR) was detected in two-thirds of the subjects >30 years old.
      Tricuspid regurgitation (TR) was frequently (>80%) detected in all age groups. In
      general, prevalence of valvular regurgitation was higher than those reported
      previously, except for a relatively lower prevalence of AR in the elderly
      population. Age was an independent correlate of AR and MR, but not of TR. The
      presence of AR and MR were independent correlates of TR. CONCLUSIONS: In healthy
      subjects, AR, MR or TR are commonly detected by using a current echo machine.
      These "physiological" valvular regurgitations should not be considered as a
      "pathological" valvular heart disease.

PMID- 21881248
TI  - A study of anti-inflammatory and analgesic activity of new 2,4,6-trisubstituted
      pyrimidines.
AB  - Chalcone derivatives (3a-m) were prepared by condensing 4-aminoacetophenone with
      various substituted aromatic and hetero aromatic aldehydes according to Claisen
      Schmidt condensation. These chalcones, on reaction with guanidine hydrochloride
      under basic alcoholic conditions gave 2,4,6-trisubstituted pyrimidines (5a-m) in
      quantitative yields. All the newly synthesized pyrimidines were characterized by
      means of IR, 1H- and 13C-NMR, Electron Ionization (EI)-mass and elemental
      analyses and screened for anti-inflammatory and analgesic activities by in vivo.
      2-amino-4-(4-aminophenyl)-6-(2,4-dichlorophenyl)pyrimidine (5b) and 2-amino-4-(4
      aminophenyl)-6-(3-bromophenyl) pyrimidine (5d) were found to be the most potent
      anti-inflammatory and analgesic activity compared with ibuprofen, reference
      standard. And also it was found that compound 5b identified as lead structure
      among all in both the activities. Pyrimidines which showed good anti-inflammatory
      activity also displayed better analgesic activity.

PMID- 21881249
TI  - Rapid and sensitive determination of udenafil in plasma by LC-MS/MS for
      intranasal pharmacokinetic study in rats.
AB  - A rapid and sensitive analytical method for udenafil in rat plasma was developed
      and validated using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
      This chromatographic procedure was then applied to the in vivo pharmacokinetic
      studies in rats for determining the advantages of intranasal administration of
      the drug over oral administration. Using liquid-liquid extraction (LLE), udenafil
      and the internal standard (IS) sildenafil were extracted with dichloromethane
      from 100 MUl of plasma samples. Chromatographic separation was performed using
      Pursuit XRS C18 column (50 mm * 2.1 mm, i.d., 3 MUm, Varian Inc., CA, U.S.A.)
      with an isocratic mobile phase consisting of acetonitrile and 10 mM ammonium
      acetate (90 : 10, v/v) at a flow rate of 0.2 ml/min over a total run time of 2.5
      min. Detection and quantification was performed by mass spectrometry using the
      multiple reaction-monitoring mode at m/z 517.4->283.1 for udenafil and m/z 475.3
      >100.0 for IS. Results showed that the developed method was sensitive and
      specific for udenafil. Linearity was obtained in the range of 0.5-1000 ng/ml. The
      coefficient of variation of both intra- and inter-day validation were below 11.6%
      and the intra- and inter-day accuracy ranged from 91.5 to 109.9%. Udenafil
      concentration was successfully measured from plasma after intranasal as well as
      after intravenous or oral administration at clinical dose (1.67 mg/kg) in rats.
      Moreover, the T(max) values obtained from pharmacokinetic studies suggested that
      administration of udenafil intranasally could be more effective than by the oral
      route.

PMID- 21881250
TI  - New green synthesis and formulations of acyclovir prodrugs.
AB  - Different green synthesis of alkyl esters of acyclovir (acyclovir prodrugs) is
      described. Hexanoic, decanoic, dodecanoic and tetradecanoic acyclovir esters were
      synthesized reacting acyclovir and the respective acid anhydride in dimethyl
      sulfoxide (DMSO), in solvents from renewable sources and without solvent (T=30 
      degrees C). Yields in prodrugs after 10 min of reaction were >95% using DMSO as
      solvent. The purification methodology was very simple, shorter and greener than
      previously described. The biosolvent, N,N-dimethylamide of decanoic acid, let us
      to obtain >95% yield at 24 h. This oily biosolvent is not dermotoxic and the
      reaction crude can directly be used in topic formulations. Syntheses without
      solvent proceeded successfully for acyclovir esters. Indeed, dodecanoate and
      tetradecanoate yielding >98% conversion of reactants in 30 min. In spite of
      requiring mild temperature (65  degrees C), substrate molar ratios were lowered
      to 1 : 1, thus conducing to a more efficient use of raw materials. The synthetic
      procedures were scaled up to a 300 g batch (yield 98-99% isolated ester). These
      esters can be used as acyclovir prodrugs in topic formulations. The esters
      release from an oil/water micro-emulsion and a hydrogel formulation were tested
      with good results.

PMID- 21881251
TI  - High-molecular-weight polyethyleneimine conjuncted pluronic for gene transfer
      agents.
AB  - In order to enhance the gene delivery efficiency and decrease cytotoxicity of
      polyplexes, copolymers consisting of branched polyethyleneimine (PEI) 25 kDa
      grafted with Pluronic (F127, F68, P105) were successfully synthesized using a
      simple two-step procedure. The copolymers were tested for cytotoxicity and DNA
      condensation and complexation properties. Their polyplexes with plasmid DNA were
      characterized in terms of DNA size and surface charge and transfection
      efficiency. The complex sizes were below 300 nm, which implicated their potential
      for intracellular delivery. The Pluronic-g-PEI exhibited better condensation and
      complexation properties than PEI 25 kDa. The cytotoxicity of PEI was strongly
      reduced after copolymerization. The Pluronic-g-PEI showed lower cytotoxicity in
      three different cell lines (Hela, MCF-7, and HepG2) than PEI 25 kDa. pGL3-lus was
      used as a reporter gene, and the transfection efficiency was in vitro measured in
      HeLa cells. Compared with unmodified PEI 25 kDa Pluronic-g-PEI showed much higher
      transfection efficiency. These results demonstrate that polyplexes prepared using
      a combined strategy of surface crosslinking and grafted with Pluronic seem to
      provide promising properties as stable, high transfection efficiency vectors.

PMID- 21881252
TI  - Anti-hepatitis B virus and cytotoxic diterpenoids from Isodon lophanthoides var.
      gerardianus.
AB  - Four new diterpenoides, isolophanthins A-D (1-4) together with seven known
      abietane diterpenoides (5-11), have been isolated from Isodon lophanthoides var.
      gerardianus. The new diterpenoides were elucidated by spectroscopic analysis.
      Some of them showed significant activities against HBsAg and HBeAg of hepatitis B
      virus in Hep G 2.2.15 cells, as well as the human tumor cell lines, HL-60, A-549,
      MOLT-4, and BEL-7402.

PMID- 21881253
TI  - High-performance liquid chromatographic determination and metabolic study of
      sennoside a in daiokanzoto by mouse intestinal bacteria.
AB  - Daiokanzoto (DKT, combination of rhubarb and glycyrrhiza), a Kampo medicine, is
      clinically effective for constipation. Sennoside A is well known to induce
      diarrhea. Sennoside A is a prodrug that is transformed into an active metabolite,
      rheinanthrone, by intestinal bacteria. In this study, we investigated the effects
      of glycyrrhiza on the activity of sennoside A metabolism in intestinal bacteria
      using mouse feces. A high-performance liquid chromatography (HPLC) method for the
      determination of sennoside A in incubation mixture of DKT with mouse feces was
      established. The retention time of sennoside A was 9.26+/-0.02 min with a TSKgel
      ODS-80TsQA column by linear gradient elution using a mobile phase containing
      aqueous phosphoric acid and acetonitrile and detection at 265 nm. We found that
      the activity of sennoside A metabolism in intestinal bacteria was significantly
      accelerated when glycyrrhiza, liquiritin or liquiritin apioside coexisted with
      sennoside A, whereas that of glycyrrhizin was not altered. This method is
      applicable for determination of the activity of sennoside A metabolism by
      anaerobic incubation of DKT with mouse feces.

PMID- 21881254
TI  - A risk assessment of human ether-a-go-go-related gene potassium channel
      inhibition by using lipophilicity and basicity for drug discovery.
AB  - The blockade of human ether-a-go-go-related gene (hERG) potassium channels is
      widely regarded as the predominant cause of drug-induced QT prolongation. The
      correlation analysis between the inhibition of the hERG channel (hERG inhibition)
      and physicochemical properties was investigated by use of in-house quinolone
      antibiotics as model compounds. In order to establish a simple prediction model
      of hERG inhibition, we focused on the comprehensible physicochemical parameters
      such as lipophilicity (log P) and basicity (pK(a)). At first, the risk associated
      with increasing log P and pK(a) was examined by statistical analysis. It was
      demonstrated that the risk associated with increasing log P and pK(a) by one
      unit, respectively, almost identically increased. Consequently, equal attention
      should be paid to both parameters on hERG inhibition. Next, a prediction model of
      hERG inhibition which was represented by log P and pK(a) was investigated. As a
      result, we built the stepwise discriminant prediction model which took advantage
      of the risk judgment by zone classification. In conclusion, the impact of log P
      and pK(a) on hERG inhibition was clarified relatively and quantitatively. The
      quantitative risk assessment established based on both parameters, was considered
      to be a practical and useful tool in avoiding hERG inhibition and in the rational
      drug design for drug discovery, especially in lead optimization. Moreover, we
      also carried out a trend analysis using a different derivative and demonstrated
      that both parameters were equally significant for hERG inhibition.

PMID- 21881255
TI  - Short- and long-term stability of lyophilised melatonin-loaded lecithin/chitosan
      nanoparticles.
AB  - The aim of this study was to establish a freeze-drying process for melatonin
      loaded lecithin/chitosan nanoparticles (NPs) to preserve their chemical and
      physical stability for a longer time period that what is possible in an aqueous
      suspension. Glucose and trehalose were investigated as potential excipients
      during freeze-drying of NP suspensions. Lecithin/chitosan NPs were characterised
      by mean diameter and zeta potential, ranging between 117.4 and 328.5 nm and 6.7
      and 30.2 mV, respectively, depending on the lecithin type and chitosan content in
      the preparation. Melatonin loadings were up to 7.1%. For all lecithin/chitosan
      NPs, no notable differences in the mean particle size, size distribution, zeta
      potential or melatonin content were observed before or immediately after the
      lyophilisation process or after 7 months of storage at 4  degrees C. The residual
      moisture contents of lyophilisates with glucose and trehalose immediately after
      the lyophilisation process varied between 4.0-4.8% and 2.4-3.0%, respectively.
      All lecithin/chitosan NPs had a fully amorphous nature after the freeze-drying
      process, as indicated by modulated differential scanning calorimetry. NP
      lyophilisates with glucose had a low glass transition temperature (ca. 5  degrees
      C), confirming that lyophilisation with glucose as a cryoprotectant was not
      appropriate. All lyophilisates with trehalose had a glass transition temperature
      above the room temperature, allowing formation of the cake without a collapse of
      the structure, which was capable of preserving its characteristics and appearance
      following 7 months of storage at 4  degrees C.

PMID- 21881256
TI  - Novel diphenylamine 2,4'-dicarboxamide based azoles as potential epidermal growth
      factor receptor inhibitors: synthesis and biological activity.
AB  - Several hybrid molecules of diphenylamine-2,4'-dicarboxamide with various
      azolidinones and related heterocyclic rings have been synthesized and explored as
      epidermal growth factor receptor (EGFR) kinase inhibitors. Most of them displayed
      promising in vitro tyrosine kinase inhibition as well as potent cellular
      antiproliferative activity in the EGFR over-expressing breast cancer cell line
      (MCF-7). Compounds 12b and 13b that exhibited the highest inhibition in the
      kinase assay (89, 81% inhibition at 10 MUM, respectively), showed potent
      antiproliferative effect against MCF-7 tumor cell line (IC(50) 1.04, 0.91 MUM
      respectively). Molecular docking studies revealed that these compounds can bind
      to ATP binding site of the EGFR kinase domain and were involved in H-bonding with
      Met 793, in analogy to the known EGFR tyrosine kinase inhibitors. Moreover,
      compounds 15a-c possessed profound antitumor activity (IC(50) 0.59-0.73 MUM) and
      significant EGFR-TK inhibition, making them of particular interest. In summary,
      the newly synthesized compounds provide promising new lead for the future design
      and development of anticancer agents of potential EGFR-TK inhibitory activity.

PMID- 21881257
TI  - Lewis acid-catalyzed propargylic etherification and sulfanylation from alcohols
      in MeNO2-H2O.
AB  - Direct scandium- and lanthanum-catalyzed etherifications of propargyl alcohols 1
      and 6 in MeNO2-H2O provided propargyl ethers 3, 4 and 7 in high yields. In
      addition, reactions of 1 and 6 with thiols exclusively yielded the corresponding
      propargyl sulfides.

PMID- 21881258
TI  - Dianthosaponins A-F, triterpene saponins, flavonoid glycoside, aromatic amide
      glucoside and gamma-pyrone glucoside from Dianthus japonicus.
AB  - From aerial parts of Dianthus japonicus, six new and seven known oleanane-type
      triterpene saponins were isolated. The structures of the new saponins, named
      dianthosaponins A-F, were elucidated by means of high resolution mass
      spectrometry, and extensive inspection of one- and two-dimensional NMR
      spectroscopic data. A new C-glycosyl flavone, a glycosidic derivative of
      anthranilic acid amide and a maltol glucoside were also isolated.

PMID- 21881259
TI  - Catecholthioether derivatives: preliminary study of in-vitro antimicrobial and
      antioxidant activities.
AB  - In this research, synthesis, antimicrobial and antioxidant activities of a series
      of catecholthioethers having benzoxazole and tetrazole moieties are described.
      Antimicrobial activity was evaluated by minimum inhibitory concentration (MIC)
      assay. The synthesized compounds were tested in vitro against three Gram-positive
      bacteria including Staphylococcus aureus (clinical isolated), Staphylococcus
      aureus ATCC 25922, Enterococcus faecium (clinical isolated), and two Gram
      negative bacteria including Klebsiella pneumoniae (clinical isolated) and
      Pseudomonas aeruginosa 27853 and the yeast Candida albicans in comparison with
      control drugs. Microbiological results indicated that the synthesized compounds
      possessed a broad spectrum of activity against the tested microorganisms at MIC
      values between 4-256 MUg/ml. This shows compounds having tetrazole moiety were
      the most active against Gram-negative strains, whereas compounds having
      benzoxazole moiety were more active against Gram-positive ones. Also both of them
      showed significant antifungal activity against Candida albicans and had lower
      activity than the compared control drugs (Sulfamethoxazole and Fluconazole). The
      antioxidant activity was assessed using two methods, including, 1,1-biphenyl-2
      picrylhydrazyl (DPPH) radical scavenging, and reducing power assays. Some of the
      catecholthioether derivatives showed antioxidant activity more than Trolox and
      butylated hydroxyanisole (BHA) as reference antioxidants.

PMID- 21881260
TI  - Synthesis and evaluation of antioxidant, anti-inflammatory and antiulcer activity
      of conjugates of amino acids with nifedipine.
AB  - A new series of novel (2S)-2-({2-[1,4-dihydro-3,5-bis(methoxycarbonyl)-2,6
      dimethyl-4-(2-nitrophenyl)pyridin-1-yl]-2-oxoethyl}amino)-3-(4-hydroxyphenyl)
      propanoic acid (3a) and its analogues 3b-j has been synthesized. These compounds
      were evaluated for their in vitro antioxidant activity, anti-inflammatory
      activity and antiulcer activity. Compounds 3b and f exhibited significant
      antioxidant action comparable with that of standard. Efficacy against
      inflammation and ulceration was also found to be significant. The chemical
      structures of these compounds were confirmed on the basis of spectral data.

PMID- 21881261
TI  - Pimarane diterpenes from the endophytic fungus Eutypella sp. BCC 13199.
AB  - Two new pimarane-type diterpenes, eutypellones A (1) and B (2), were isolated
      from the endophytic fungus Eutypella sp. BCC 13199. Cytotoxic activities of the
      pimaranes 1-5, isolated from this fungus, were evaluated.

PMID- 21881262
TI  - 3-Hydroxydihydrobenzofuran glucosides from Gnaphalium polycaulon.
AB  - A new 3-hydroxydihydrobenzofuran glucoside, gnaphaliol 9-O-beta-D-glucopyranoside
      (2), was isolated from the aerial parts of Gnaphalium polycaulon together with 1
      {(2R*,3S*-3-(beta-D-glucopyranosyloxy)-2,3-dihydro-2-[1-(hydroxyl methyl)vinyl]-1
      benzofuran-5-yl}-ethanone or gnaphaliol 3-O-beta-D-glucopyranoside (1), (Z)-3
      hexenyl O-beta-D-glucopyranoside (3) and adenosine (4). The absolute
      configurations at C-2 and C-3 positions of compound 1 were determined to be 2R
      and 3R. The structures of these compounds were elucidated on the basis of their
      physical and spectroscopic data.

PMID- 21881263
TI  - Identification and characterization of component organic and glycosidic acids of
      crude resin glycoside fraction from Calystegia soldanella.
AB  - Alkaline hydrolysis of the crude resin glycoside fraction of the leaves, stems,
      and roots of Calystegia soldanella ROEM. et SCHULT. (Convolvulaceae) gave four
      new glycosidic acids, named calysolic acids A, B, C, and D, along with one known
      glycosidic acid, soldanellic acid B, and three organic acids, 2S-methylbutyric,
      tiglic, and 2S,3S-nilic acids. The structures of the new glycosidic acids were
      characterized on the basis of spectroscopic data and chemical evidence.

PMID- 21881264
TI  - Application of ring-closing metathesis for the synthesis of benzo[3,4]azepino[1,2
      b]isoquinolin-9-ones.
AB  - Cycloaddition reaction between toluamides and benzonitriles was applied to
      prepare the 3-arylisoquinolines, and their chemical transformation to the dienes
      4 was performed. The ring-closing metathesis (RCM) reaction afforded the desired
      heterocyclic compounds, benzo[3,4]azepino[1,2-b]isoquinolinones 5 in good yield.

PMID- 21881265
TI  - Flavusides A and B, antibacterial cerebrosides from the marine-derived fungus
      Aspergillus flavus.
AB  - Flavusides A (1) and B (2), two new antibacterial cerebroside derivatives, and
      the previously described phomaligol A (3), kojic acid (4), methyl kojic acid (5),
      and dimethyl kojic acid (6) have been isolated from the extract of a marine
      isolate of the fungus Aspergillus flavus. The structure and absolute
      stereochemistry of two cerebrosides were assigned on the basis of NMR and Tandem
      FAB-MS/MS experiments. Compounds 1, 2, and 3 exhibited a mild antibacterial
      activity against Staphylococcus aureus, methicillin-resistant S. aureus, and
      multidrug-resistant S. aureus. The minimum inhibitory concentration (MIC) values
      for each strain are as follows: compounds 1 and 2 showed 15.6 MUg/ml for S.
      aureus and 31.2 MUg/ml for methicillin-resistant S. aureus and multidrug
      resistant S. aureus, and compound 3 exhibited 31.2 MUg/ml for S. aureus and
      methicillin-resistant S. aureus and 62.5 MUg/ml for multidrug-resistant S.
      aureus.

PMID- 21881266
TI  - A new hypoxia inducible factor-2 inhibitory pyrrolinone alkaloid from roots and
      stems of Piper sarmentosum.
AB  - A new trimethoxycinnamoyl-2-pyrrolinone alkaloid, langkamide (1), along with the
      known compounds piplartine (2) and 3,4,5-trimethoxycinnamic acid (3) were
      isolated from the roots and stems of the shrub Piper sarmentosum ROXB. The
      structures were established by spectroscopic analyses and comparison of their
      spectral data with values reported in the literature. The compounds were tested
      for their ability to modulate hypoxia inducible factor-2 (HIF-2) transcription
      activity and all three showed HIF-2 inhibitory activity with EC50 values of 14.0,
      4.8, and 60.6 MUM, respectively, for compounds 1, 2, and 3.

PMID- 21881267
TI  - Biotransformation of ursolic acid by an endophytic fungus from medicinal plant
      Huperzia serrata.
AB  - Endophytic fungi were used not only for their producing bioactive products but
      also for their ability to transform natural compounds. An endophytic fungus,
      isolated from medicinal plant Huperzia serrata, was identified as Umbelopsis
      isabellina based on the internal transcribed spacer of ribosomal DNA (rDNA-ITS)
      region. It was used to transform ursolic acid (1), a pentacyclic triterpene.
      Incubation of ursolic acid with U. isabellina afforded three products, 3beta
      hydroxy-urs-11-en-28,13-lactone (2), 3beta,7beta-dihydroxy-urs-11-en-28,13
      lactone (3), 1beta,3beta-dihydroxy-urs-11-en-28,13-lactone (4). Although product
      2 was a known compound, it was first obtained by microbial transformation.
      Products 3 and 4 were new compounds. The structural elucidation of the three
      compounds was achieved mainly by the 1D- and 2D-NMR, MS, IR data. The endophytic
      fungus U. isabellina can hydroxyate the C12-C13 double bond at position 13 of
      ursolic acid 1 and form a five-member lactone effectively. In the meantime, this
      fungus can also introduce the hydroxyl group at C-1 or C-7 of ursolic acid 1.

PMID- 21881268
TI  - Biomimetic one-pot preparation of a black tea polyphenol theasinensin A from
      epigallocatechin gallate by treatment with copper(II) chloride and ascorbic acid.
AB  - Chromatographic separation of black tea polyphenols is too difficult to supply
      sufficient quantities of pure compounds for biological experiments. Thus, facile
      methods to prepare black tea constituents were desired. Treatment of
      epigallocatechin gallate with copper(II) chloride efficiently afforded an
      unstable quinone dimer, dehydrotheasinensin A, and subsequent treatment with
      ascorbic acid stereoselectively yielded theasinensin A. The latter is a dimer
      with an R-biphenyl bond, one of the major polyphenols found in black tea. The
      method is simpler and more effective than enzymatic preparation.

PMID- 21881269
TI  - Synthesis and cytotoxic evaluation of eremophilane sesquiterpene 07H239-A
      derivatives.
AB  - Nine new derivatives (6-14) of the eremophilane sesquiterpene 07H239-A (5) were
      designed and semisynthesized with two types of R-groups by amidation. Most of
      them were active against five human tumor cell lines, and compounds 6-10 were
      more potent than the natural product 5. In particular, compounds 6 and 9
      exhibited the strongest cytotoxic activity against MDA-MB-435 with IC50 values of
      0.91 and 0.96 MUM, respectively. Preliminary structure-activity relationships
      (SARs) analysis indicated that the 14-carboxyl in 5 was an ideal target for
      chemical modification, and the side chain of 5 might play a necessary role in
      facilitating their cytotoxic potencies.

PMID- 21881270
TI  - Formal (3+3) cycloaddition of silyl enol ethers catalyzed by trifric imide:
      domino Michael addition-claisen condensation accompanied with isomerization of
      silyl enol ethers.
AB  - We describe here a Tf2NH-catalyzed formal (3+3) cycloaddition of silyl enol
      ethers with acrylates as a new domino reaction. In the domino sequence, the
      catalyst activates Michael addition, deprotonation of the resulting silyloxonium
      cation and intramolecular Claisen condensation. It was found that reaction modes
      significantly depend on the reaction temperature. We also examined the
      mechanistic detail of the reaction by 1H-NMR experiment.

PMID- 21881271
TI  - Two new cytotoxic phenylallylflavanones from Mexican propolis.
AB  - Two new phenylallylflavanones, (2R,3R)-6-[1-(4'-hydroxy-3'-methoxyphenyl)prop-2
      en-1-yl]pinobanksin (1) and (2R,3R)-6-[1-(4'-hydroxy-3'-methoxyphenyl)prop-2-en-1
      yl]pinobanksin 3-acetate (2) were isolated from a methanolic extract of Mexican
      propolis. Their structures were elucidated with spectroscopic analysis. Both
      compounds (1, 2) exhibited preferential cytotoxic activity against PANC-1 human
      pancreatic cancer cells in a nutrient-deprived medium with the concentration at
      which 50% cells died preferentially in NDM (PC50) values of 17.9 MUM and 9.1 MUM,
      respectively.

PMID- 21881272
TI  - Prediction of three-independent scales endowed on poliovirus proteinase 2A
      sequence.
AB  - Mulliken's electronegativity (M) scale was found as a parameterization to predict
      (elucidate) a virtually specific interaction between Poliovirus proteinase 2A and
      mitogen-activated protein (MAP) kinase p38alpha, as well as that between the 2A
      and apoptotic protein activating factor 1c (Apaf 1c) (or prion) with
      intermolecular frequency symmetry (IFS) rule. Also, Lacey's hydropathical (H)
      scale and Garel's (G) one could be found in the specific relationship between the
      2A and the extracellular signal-regulated kinase 2 (ERK2) [or fibroblast growth
      factor receptor 3 (FGFR3)], and that between the 2A and the c-Jun N-terminal
      kinase 2 (JNK2) [or forkhead box P2-1 (FOXP2-1)], respectively. Based on these,
      both the same physicochemical scale and almost the same resonant frequency (f)
      value would be conserved in the same succession of a signal transduction process
      in a Poliovirus-infected cell. Furthermore, the 2A could play a trigger role to
      cause cancer, prion disease, bone disease, or speech and language disorder.

PMID- 21881273
TI  - Characterization of novel pH-sensitive polymeric micelles prepared by the self
      assembly of amphiphilic block copolymer with poly-4-vinylpyridine block
      synthesized by mechanochemical solid-state polymerization.
AB  - We fabricated novel pH-sensitive polymeric micelles consisting of amphiphilic
      block copolymer containing pyridyl groups as side chains in the hydrophobic
      block. The number average particle diameter of the polymeric micelles at pH 7 was
      approximately 200 nm. A decrease in pH resulted in deformation of the polymeric
      micelles over a very narrow pH range (between pH 5.7 and 5.6). Interestingly,
      micellization and demicellization occurred reversibly in this narrow pH range.
      Polymeric micelles incorporating 5-fluorouracil (5FU) were also prepared.
      Decreasing the pH of this polymeric micelle solution from 7 to 5.5 resulted in
      the rapid release of 5FU at pH 5.6; the drug was completely released within 30
      min. These results suggest that deformation of the polymeric micelles caused the
      rapid release of 5FU.

PMID- 21881274
TI  - Identification of a novel cannabimimetic phenylacetylindole,
      cannabipiperidiethanone, as a designer drug in a herbal product and its affinity
      for cannabinoid CB1 and CB2 receptors.
AB  - A new cannabimimetic phenylacetylindole (cannabipiperidiethanone, 1) has been
      found as an adulterant in a herbal product which contains two other known
      synthetic cannabinoids, JWH-122 and JWH-081, and which is distributed illegally
      in Japan. The identification was based on analyses using GC-MS, LC-MS, high
      resolution MS and NMR. Accurate mass spectrum measurement showed the protonated
      molecular ion peak of 1 at m/z 377.2233 [M+H]+ and the molecular formula of 1 was
      C24H29N2O2. Both mass and NMR spectrometric data revealed that 1 was 2-(2
      methoxyphenyl)-1-{1-[(1-methylpiperidin-2-yl)methyl]-1H-indol-3-yl}ethanone.
      Compound 1 has a mixed structure of known cannabimimetic compounds: JWH-250 and
      AM-2233. Namely, the moiety of phenylacetyl indole and N-methylpiperidin-2-yl
      methyl correspond to the structure of JWH-250 and AM-2233, respectively. However,
      no synthetic, chemical or biological information about 1 has been reported. A
      binding assay of compound 1 to cannabinoid receptors revealed that 1 has affinity
      for the CB1 and CB2 (IC50=591, 968 nM, respectively) receptors, and shows 2.3-
      and 9.4-fold lower affinities than those of JWH-250. This is the first report to
      identify cannabimimetic compound (1) as a designer drug and to show its binding
      affinity to cannabinoid receptors.

PMID- 21881275
TI  - Palladium-catalyzed cross coupling reaction of N-alkoxyimidoyl bromides and its
      application to one-pot synthesis of N-arylamines.
AB  - The synthetic utility of N-alkoxyimidoyl halides is demonstrated using the
      palladium-catalyzed cross-coupling reaction. The Sonogashira and Suzuki-Miyaura
      coupling reactions of N-alkoxyimidoyl bromides produced versatile ketoxime ethers
      in good to excellent yields. A one-pot reaction of the imidoyl bromides with
      arylboronic acid and allylmagnesium bromide to produce N-arylamines via Suzuki
      Miyaura coupling followed by domino reaction involving sequential addition
      eliminative rearrangement-addition reactions was developed.

PMID- 21881276
TI  - Circulating microRNAs are promising novel biomarkers of acute myocardial
      infarction.
AB  - OBJECTIVE: Recent studies have revealed that microRNAs (miRNAs) are involved in
      the regulation of cardiac development, physiologic, and pathologic processes via
      post-transcriptional control of gene expression. The stable circulating miRNAs
      offer unique opportunities for the early diagnosis of several diseases. In this
      study, we examined the circulating miR-133 and miR-328 levels from patients with
      acute myocardial infarction (AMI). PATIENTS AND METHODS: Twenty-eight control
      subjects and fifty-one consecutive AMI patients were enrolled. The plasma and
      whole blood samples from AMI patients were obtained within 24 hours (n=51) and 7
      days (n=6) after the onset of AMI symptoms. The circulating miR-133 and miR-328
      levels were analyzed using quantitative real-time PCR. RESULTS: The miR-133
      levels in plasma from AMI patients exhibited a 4.4-fold increase compared with
      control subjects (p=0.006). Moreover, the increased miR-133 levels in whole blood
      were comparable with those in plasma samples. In contrast, the miR-328 levels in
      plasma and whole blood of AMI patients were markedly increased by 10.9-fold and
      16.1-fold, respectively, compared to those in control subjects (p=0.033 and
      p<0.001). The elevated circulating miR-133 and miR-328 levels were recovered to
      the control levels at 7 days after AMI. In addition, there was a correlation
      between circulating miR-133 or miR-328 levels and cardiac troponin I.
      Furthermore, circulating miR-133 or miR-328 showed no significant changes in AMI
      patients with tachyarrhythmia (n=24) or bradyarrhythmia (n=26) compared to those
      in patients without arrhythmias. Receiver operating characteristic curve analysis
      revealed that the areas under the curve of miR-133 or miR-328 in plasma and whole
      blood were 0.890, 0.702 and 0.810, 0.872, respectively (all p<0.05). CONCLUSION:
      The miR-133 and miR-328 levels in plasma and whole blood in AMI patients were
      increased compared to those in control subjects. These miRNAs may represent novel
      biomarkers of AMI.

PMID- 21881277
TI  - Analysis of cardiovascular disease in Chinese inpatients with chronic kidney
      disease.
AB  - OBJECTIVE: To investigate the prevalence of cardiovascular disease (CVD) in a
      Chinese patient population with different stages of chronic kidney disease (CKD).
      METHODS: Six hundred and two CKD patients who were hospitalized in Ruijin
      Hospital between Jan. 2004 and Jan. 2006 were selected. Patients' medical
      histories and the results of laboratory tests were reviewed. RESULTS: The
      prevalence of CVD in 602 patients with CKD stages 1 to 5 was 1.28%, 17.24%,
      22.86%, 33.33%, 56.2% respectively. The prevalence of CVD in CKD stage 5 patients
      with dialysis was 78.51%. In all the patients, the prevalence of coronary artery
      disease (CAD), left ventricular hypertrophy (LVH), and congestive heart failure
      (CHF) was 8.64% (52/602), 26% (154/602), and 13% (78/602), respectively.
      Regarding co-morbidities of CVD, 34.52% of patients had 2 or more of the above
      abnormalities. The prevalence of CAD in patients with CKD stages 1 to 5
      respectively was 1.28%, 5.75%, 7.86%, 10.26%, 12.33%;LVH was 0%, 11.49%, 16.43%,
      29.49%, 44.75%; and CHF was 0%, 3.45%, 3.57%, 8.97%, 28.77%. CONCLUSION: The
      occurrence of CVD started from CKD stage 1 and increased with the progression of
      CKD. The screening and prevention of CVD should begin at CKD stage 1.

PMID- 21881278
TI  - Prognosis in adult patients with idiopathic pulmonary hemosiderosis.
AB  - BACKGROUND: Diffuse alveolar hemorrhage (DAH) of unknown cause has been
      characterized as idiopathic pulmonary hemosiderosis (IPH). IPH is a rare disease,
      which has a high prevalence in children and shows a poor prognosis. However, in
      adults, since there are few reports about collective cases, the details remain to
      be determined. METHODS: Between January 2003 and June 2008, consecutive adult
      patients strictly defined as unknown cause DAH by chest images, fiberoptic
      bronchoscopy, autoantibody testing, and exclusion of systemic disease were
      enrolled. We investigated the clinical characterization and course of the
      enrolled patients. RESULTS: Nine patients were included. All patients were middle
      aged men (56.1 +/- 4.2 year-old) with sudden onset. They did not present with
      anemia (the hemoglobin level was 13.9 +/- 0.5 g/dL) despite the quantity of
      bleeding. In bronchoalveolar-lavage fluid analysis, the cell count was increased
      (7.6 +/- 1.6*10(5) cells/mL) with neutorophilia (33.3 +/- 13.3%). The illness
      resolved within 2 weeks with or without corticosteroid therapy. All of the
      patients were alive without recurrence during the follow-up period (45.2 +/- 6.2
      months) after diagnosis. CONCLUSION: Adult IPH patients showed good prognosis.
      However, the present patients are clinically slightly different from the
      previously characterized IPH.

PMID- 21881279
TI  - Relationship between computed tomography findings and nutritional status in
      elderly patients with pulmonary tuberculosis.
AB  - OBJECTIVE: This study was aimed to identify the relationship between radiographic
      features of elderly pulmonary TB patients and nutritional deficiency. METHODS:
      Ninety-two patients older than 70 years of age with pulmonary TB were
      retrospectively enrolled. The influence of nutritional parameters, such as serum
      albumin concentration and peripheral blood total lymphocyte count on CT findings
      was examined. CT findings of pulmonary TB patients were classified as those
      including atypical findings (segmental or lobar consolidation in an unusual
      location, miliary nodules, and hilar and mediastinal lymphadenopathy) or not. The
      number of segments involved by TB was also counted. RESULTS: Age- and gender
      adjusted analyses for the nutritional parameters and confounders revealed that
      hypoalbuminemia, lymphocytopenia, and steroid therapy were significantly related
      to the presence of atypical CT findings. Furthermore, hypoalbuminemia,
      lymphocytopenia, and the amount of acid-fast bacilli in sputum smears were
      significantly related to an increased number of involved segments. In
      multivariate analysis, only hypoalbuminemia was significantly related to the
      presence of atypical CT findings (OR: 0.335, 95% CI: 0.142-0.794, p = 0.013) and
      an increased number of involved segments (OR: 0.145, 95% CI: 0.047-0.453, p =
      0.0009). Among the CT findings, the tree-in-bud pattern was the most common in
      all patients (79.3%). However, the presence of the tree-in-bud pattern was not
      significantly related to any nutritional parameter. CONCLUSION: Elderly TB
      patients of poor nutritional status, in particular those with hypoalbuminemia,
      tended to show atypical CT findings and widespread lesions. The tree-in-bud
      pulmonary pattern could be observed in TB patients in any nutritional state.

PMID- 21881280
TI  - A case of pyogenic liver abscess infected with Fusobacterium necrophorum depicted
      by microscopy and confirmed by tissue culture.
AB  - A 40-year-old man was admitted with a continuous high grade fever accompanying a
      relatively large solitary liver abscess with septations. A puncture of the
      abscess revealed gram-negative rods that could be identified histologically as
      Fusobacterium necrophorum, which was later confirmed by tissue culture. The
      patient was switched to meropenem and penicillin, and cured of the infection.
      Fusobacterium necrophorum is a rare bacterium causing potentially fatal liver
      abscesses in humans. Clinicians should bear Fusobacterium necrophorum in mind
      when treating patients with an enlarged solitary liver abscess.

PMID- 21881281
TI  - Treatment of a case of mesangioproliferative glomerulonephritis secondary to
      Echinococcus alveolaris with albendazole.
AB  - Parasitic infections lead to significant morbidity and mortality, especially in
      tropical regions. The renal damage caused by these infections occurs via various
      mechanisms. Two forms of parasitic echinococcus infection widely responsible for
      infection in humans are Echinococcus granulosus and Echinococcus multilocularis.
      E. multilocularis causes Alveolar echinococcus infection in humans. Alveolar
      echinococcus has high mortality, and the possible limits of surgery are generally
      exceeded by the time of diagnosis. The literature contains no case reports of
      comorbidity of alveolar echinococcus and glomerulonephritis. Here we discuss the
      treatment of a patient with comorbid mesangioproliferative glomerulonephritis and
      alveolar echinococcus, behaving like a tumor, using albendazole since there was
      no possibility of surgery. This is the first ever such case report.

PMID- 21881282
TI  - Thrombotic microangiopathy associated with tuberculous infection.
AB  - A 32-year-old man was diagnosed as having thrombotic microangiopathy (TMA) and
      treated by plasma exchange (PE). During the course of admission, he was also
      newly diagnosed with pulmonary tuberculosis, tuberculous peritonitis and
      pleuritis, which was thought to be the cause of the TMA. There are only a few
      previous reports on TMA associated with tuberculous infection. Although its
      pathogenetic mechanism is not well understood, it would be valuable to recognize
      that this worldwide infectious disease could cause TMA.

PMID- 21881283
TI  - Swyer-James syndrome with peculiar course and ipsilateral pulmonary vein defect.
AB  - Swyer-James syndrome (SJS) is a rare disease probably resulting from
      bronchiolitis obliterans. The radiological findings of this entity are
      characterized by hyperlucent appearance of one or more lobes of a unilateral
      lung, decreased lung volume, diminished ipsilateral hilar shadow and hardly
      visible arterial structure on chest radiography. We report a 50-year-old patient,
      who had unilateral right lower lung hyperlucency on chest radiography. However,
      the patient reported a history of pulmonary atelectasis of lobus centralis dexter
      in the course and the corresponding affliction of ipsilateral pulmonary vein,
      that rendered the diagnosis more complicated. The radiological and pathological
      features of this syndrome, as well as differential diagnosis were also discussed.

PMID- 21881284
TI  - Intestinal perforation due to concomitant cytomegalovirus infection during
      treatment for Pneumocystis jirovecii pneumonia in a patient with rheumatoid
      arthritis.
AB  - A 78-year-old woman with rheumatoid arthritis treated with methotrexate and
      corticosteroid was admitted to our hospital for dry cough and dyspnea. She was
      diagnosed as having Pneumocystis pneumonia based on elevated beta-D-glucan and
      positive PCR analysis of bronchoalveolar lavage fluid for Pneumocystis jirovecii.
      We started trimethoprim-sulfamethoxazole and high-dose corticosteroid therapy.
      Her pulmonary lesions gradually improved; however, she developed perforation of
      the ileum and subsequently died from sepsis. Histology of the perforated site was
      compatible with cytomegalovirus enterocolitis.

PMID- 21881285
TI  - Spinal segmental myoclonus during postural maintenance in a patient with cervical
      spondylosis: a case report.
AB  - Spinal segmental myoclonus is defined as a rare involuntary movement
      characterized by myoclonic jerks of spinal origin. We describe the case of a 62
      year-old woman who developed spinal segmental myoclonus 4 months after undergoing
      cervical laminoplasty for ossification of the posterior longitudinal ligament.
      Myoclonic jerks were observed in the upper trapezius innervated by C3-4, which
      corresponded to the level of myelomalacia. These jerks were elicited and
      aggravated in the sitting and standing positions but were completely suppressed
      in the supine position. The myoclonus was refractory to medication but improved
      with the use of a soft neck brace.

PMID- 21881286
TI  - Etanercept-induced lupus accompanied by hemophagocytic syndrome.
AB  - Hemophagocytic syndrome (HPS) is a severe, potentially life-threatening disorder
      characterized by an excessive activation of macrophages, such as may occur in the
      setting of lupus. A 62-year-old Japanese woman treated with etanercept for
      rheumatoid arthritis developed persistent fever, cytopenia, coagulopathy, and
      hyperferritinemia. Simultaneously, lupus-like features including pleuritis,
      hypocomplementemia, and positive autoantibodies were observed. She was diagnosed
      with HPS related to etanercept-induced lupus, and underwent immunosuppressive
      therapy with successful recovery. To our knowledge, this is the first case of
      etanercept-induced lupus accompanied by HPS. This case suggests that HPS should
      be considered as a complication during TNF-alpha inhibitor therapy.

PMID- 21881287
TI  - Successful treatment of HTLV-1-related overlap syndrome using tacrolimus.
AB  - A 56-year-old HTLV-I-positive woman, initially diagnosed as having Sjogren's
      syndrome, presented with muscle weakness, myalgia, face erythema and leg edema.
      Based on the presence of various autoantibodies, the diagnosis of overlap
      syndrome (dermatomyositis/Sjogren's syndrome) was made. Treatment with high-dose
      corticosteroid plus cyclosporine improved her symptoms. However, three months
      after the start of these treatments, exacerbation of myositis occurred. A muscle
      biopsy revealed prominent perivascular accumulation of mononuclear cells with
      perifascicular atrophy, which were consistent with dermatomyositis. Tacrolimus,
      which was substituted for cyclosporine led to marked improvement of the myositis
      symptoms.

PMID- 21881288
TI  - Small muco-submucosal elongated polyp of the sigmoid colon.

PMID- 21881289
TI  - Intramyocardial calcification with mitral annular calcification.

PMID- 21881290
TI  - Sudden cardiac arrest after subarachnoid hemorrhage.

PMID- 21881291
TI  - Callus formation in a patient with Cushing's syndrome.

PMID- 21881292
TI  - Isolated lateropulsion caused by a paramedian midbrain infarction.

PMID- 21881293
TI  - Pure sensory stroke due to pontine tegmentum infarction.

PMID- 21881294
TI  - Hot liver sign: an indicator of a grave prognosis.

PMID- 21881295
TI  - Preventive effects of an enriched environment on rodent psychiatric disorder
      models.
AB  - Interplay between genetic and environmental factors plays a key role in
      psychiatric disorders, as well as other brain diseases, cancer, and metabolic
      syndrome. In accordance with epidemiological findings, animal studies have
      pointed out the importance of a variety of environmental factors, such as viral
      infection during pregnancy or infancy, early parental loss or separation, and
      physical or sexual abuse in early life, in the etiology of psychiatric disorders.
      Conversely, positive effects of environmental factors against the pathogenesis of
      psychiatric disorders are also demonstrated, in which most of the animals are
      exposed to an "enriched environment". This review summarizes recent progress of
      research in this field focusing on the preventive effects of an "enriched
      environment" against the expression of behavioral abnormalities in rodent models
      of psychiatric disorders.

PMID- 21881296
TI  - Acquired radioresistance of cancer and the AKT/GSK3beta/cyclin D1 overexpression
      cycle.
AB  - Fractionated radiotherapy (RT) is widely used in cancer therapy for its
      advantages in the preservation of normal tissues. However, repopulation of
      surviving tumor cells during fractionated RT limits the efficacy of RT. In fact,
      repopulating tumors often acquire radioresistance and this is the major cause of
      failure of RT. We have recently demonstrated that human tumor cells acquire
      radioresistance when exposed to fractionated radiation (FR) of X-rays every 12
      hours for 1 month. The acquired radioresistance was associated with
      overexpression of cyclin D1, a result of a series of molecular changes;
      constitutive activation of DNA-PK and AKT with concomitant down-regulation of
      glycogen synthase kinase-3beta (GSK3beta) which results in suppression of cyclin
      D1 proteolysis. Aberrant cyclin D1 overexpression in S-phase induced DNA double
      strand breaks which activated DNA-PK and established the vicious cycle of cycling
      D1 overexpression. This overexpression of cyclin D1 is responsible for the
      radioresistance phenotype of long-term FR cells, since this phenotype was
      completely abrogated by treatment of FR cells by the API-2, an AKT inhibitor or
      by a Cdk4 inhibitor. Thus, targeting the AKT/GSK3beta/cyclin D1/Cdk4 pathway can
      be an efficient modality to suppress acquired radioresistance of tumor cells. In
      this article, I overview the newly discovered molecular mechanisms underlying
      acquired radioresistance of tumor cells induced by FR, and propose a strategy for
      eradication of tumors using fractionated RT by overcoming tumor radioresistance.

PMID- 21881297
TI  - The radiotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin
      treatment is an effective therapeutic option in patients with advanced or
      metastatic bladder cancer.
AB  - The objectives of this study were to determine the tolerability of combined use
      of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with external
      beam radiation therapy (EBRT) and to access the efficacy in patients with locally
      advanced or metastatic bladder cancer. From December 2000 to November 2010, 30
      eligible patients were enrolled in this study. After receiving one cycle of MVAC
      treatment, all patients received EBRT with a half dose of MVAC treatment followed
      by two more cycles of chemotherapy. A standard fractionation with daily dose of
      1.8-2.0 Gy was used, with the total dose up to 60 Gy over 5-6 weeks. The four
      field box technique was utilized for radiation fields. Thirteen patients (43%)
      had complete response and 11 (37%) had partial response, with an overall response
      rate of 80%. The median overall survival and progression-free survival was 25.5
      months and 12.8 months, respectively. In the complete-response patients, median
      overall survival was 37.1 months. Grade 3 or 4 neutropenia occurred in 25
      patients (83%), but there were no severe infections. One patient (3%) had
      hemorrhagic radiation cystitis. There were no treatment-related deaths. Combined
      use of MVAC treatment with EBRT is a favorable therapeutic option for patients
      with advanced or metastatic bladder carcinoma. Given the safety and benefit
      profile found in this study, appropriate case selection is warranted in the
      future.

PMID- 21881298
TI  - Intrafractional gastric motion and interfractional stomach deformity using CT
      images.
AB  - To evaluate the intra- and interfractional gastric motion using repeated CT
      scans, six consecutive patients with gastric lymphoma treated at our institution
      between 2006 and 2008 were included in this study. We performed a simulation and
      delivered RT before lunch after an overnight fast to minimize the stomach volume.
      These patients underwent repeated CT scanning at mild inhale and exhale before
      their course of treatment. The repeated CT scans were matched on bony anatomy to
      the planning scan. The center of stomach was determined in the X (lateral), Y
      (superior-inferior), and Z (ventro-dorsal) coordinate system to evaluate the
      intra- and interfractional motion of the stomach on each CT scan. We then
      calculated the treatment margins. Each patient was evaluated four to five times
      before their course of RT. The average intrafractional motions were -12.1, 2.4
      and 4.6 mm for the superior-inferior (SI), lateral (LAT), and ventro-dorsal (VD)
      direction. The average interfractional motions of the center of the stomach were 
      4.1, 1.9 and 1.5 mm for the SI, LAT and VD direction. The average of the vector
      length was 13.0 mm. The systematic and random errors in SI direction were 5.1,
      and 4.6 mm, respectively. The corresponding figures in LAT and VD directions were
      10.9, 5.4, 10.0, and 6.5 mm, respectively. Thus, the 15.9, 31.0 and 29.6 mm of
      margins are required for the SI, LAT, and VD directions, respectively. We have
      demonstrated not only intrafractional stomach motion, but also interfractional
      motion is considerable.

PMID- 21881299
TI  - Investigation on traditional medicines of Guarany Indio and studies on diterpenes
      from Scoparia dulcis.
AB  - In interviews on the traditional herbal medicines of Tupi-Guarany Indians at the
      herbal market of Asuncion and questionnaire from their users, it was clarified
      that various useful medicinal plants are available in Paraguay and most of them
      are generally used without drying. In the search for bioactive substances from
      those plants, a beta-glucuronidase-inhibitory diterpene called scoparic acid A
      (SA) was isolated from Scoparia dulcis L. together with scoparic acid B, scoparic
      acid C, and the aphidicolin-like tetracyclic diterpenes scopadulcic acid A (SDA)
      and scopadulcic acid B (SDB). HPLC analysis of diterpenes in the individual
      plants of Paraguayan and Asian S. dulcis revealed the presence of three
      chemotypes based on major component, i.e., SA type, SDB type, and SDX type
      containing mainly scopadiol and scopadulciol (SDC). SA and SDB were elucidated to
      be mainly biosynthesized in the leaves via 2-C-methyl-D-erythritol- 4-phosphate
      pathway, and a leaf organ culture system containing methyl jasmonate 10 uM was
      found to enhance the production of diterpenes by activation of Ca-signal
      transduction systems such as calmodulin and protein kinase C. On the other hand,
      SDB and SDC were found to show multifaceted pharmacological effects such as
      inhibitory effects on gastric acid excretion, bone resorption, replication of
      herpes simplex virus type 1 (HSV-1), etc. In addition, SDC was suggested to be
      applicable to cancer gene therapy using ganciclovir or acyclovir and the HSV-1
      thymidine kinase gene called the suicide gene.

PMID- 21881300
TI  - Drug discovery by formulation design and innovative drug delivery systems (DDS).
AB  - This review describes studies on drug discovery using a rational formulation
      design and innovative, drug delivery systems (DDS) for biomaterials such as
      therapeutic peptides and nucleotides. The microcapsules of the LH-RH superagonist
      leuprorelin acetate prepared using the new in-water drying method and
      biodegradable polymers, such as PLGA and PLA, could achieve a long-term sustained
      release for 1-6 months thereby facilitating easily treatment of hormone-dependent
      diseases, prostate cancer, endometriosis, and precocious puberty. This DDS
      technology showed an improvement in patient QOL and highly promoted the clinical
      value of the agonist. Moreover, PLGA microcapsules of siRNAs against VEGF, cFLIP,
      Raf-1, and Int6 have also been developed to treat various cancers and
      arteriosclerosis obliterans. To develop therapeutic nucleotides, a particle
      design is created using functional peptides, such as cell penetrating peptides
      (CPP), nuclear localizing signals (NLS), tight junction reversible openers
      (AT1002), bombesin, and dynein light chain-associated sequences. siRNA use should
      lead to a paradigm shift in drug discovery against various diseases. Tat analog
      with NLS could enhance the potency of a vaginal DNA vaccine. The artificial Tat
      CPP of STR-CH(2)R(4)H(2)C synthesized in our laboratory could efficiently deliver
      siRNAs into many types of cells and enhance the therapeutic effects for treating
      sarcoma, atopic dermatitis, allergic rhinitis, and asthma by intratumor injection
      and inhalation of the nanoparticles. Tat and AT1002 analogs used to treat atopic
      dermatitis in mice increased cell membrane permeability to siRelA, a siRNA
      against a subclass of NF-kappaB, and exhibited striking therapeutic and
      preventive effects.

PMID- 21881301
TI  - Novel approach to curatives of Mibyou (presymptomatic diseases).
AB  - The traditional Oriental medicine and health supplement have been empirically
      practiced but most of them have not come through objective examination to prove
      their efficacy. From pharmacological aspect, we have been investigating the
      medical benefits of traditional Oriental medicines and health supplements as
      curatives and their varied actions and mechanisms. The study on airway
      inflammation has shown that even a Kampo preparation, Bakumondo-to, has anti
      inflammatory, anti-allergic, immunomodulatory, secretory-modulating and metabolic
      regulatory actions. The base of all its actions is founded on the restoration of
      normal molecular and cellular functions through DNA transcriptional regulation.
      In other previous studies, we showed that a health supplement, royal jelly (RJ)
      has weak estrogenic activity. RJ competes with 17beta-estradiol for binding to
      the human estrogen receptors alpha and beta, though it is much weaker than
      diethylstilbestrol in binding affinity. Treatment of MCF-7 cells with RJ enhances
      proliferation, and concomitant treatment with tamoxifen blocked this effect. A
      reporter gene assay showed that RJ enhanced transcription of the luciferase gene
      through the estrogen-responsive element in MCF-7 cells. Furthermore, subcutaneous
      injection of RJ restored the expression of vascular endothelial growth factor
      gene in the uteri of ovariectomized rats. We suggest that the diverse
      pharmacological functions of RJ can be ascribed, in part, to its estrogenic
      effects. We hypothesize that polyherbal medicines and health supplements, which
      have multiple actions, may be better than Western medicine of single component to
      treat various diseases including 'Mibyou' (presymptomatic disease). Our findings
      provide us with a new idea on the nature of disorder and disease-state
      development which involve complicated mechanisms and will contribute to novel
      principles to prevent diseases and establish new treatment. Adoption of means of
      translational research should provide objective background for efficacy and
      stimulate broader application and usage of traditional medicines and health
      supplements as curatives of Mibyou.

PMID- 21881302
TI  - Inhibition mechanism of trypsin by Schiff base metal chelate inhibitors.
AB  - Studies on trypsin-specific compounds are useful for the design of clinically
      useful compounds. It is well known that several benzamidine derivatives are
      potent competitive inhibitors of trypsin and trypsin-like enzymes. Many kinds of
      Schiff base metal chelate containing either amidine or guanidine have been
      synthesized and their inhibitory activities against trypsin have been
      characterized. Recently, the interactions of the Schiff base metal chelate
      inhibitors with trypsin enzyme have been determined by X-ray crystal structure
      analysis. The structural information and inhibitory activity data for amidine-
      and guanidine-containig Schiff base metal chelate inhibitors provide new avenues
      for designing novel inhibitors against physiologically important trypsin-like
      serine proteases.

PMID- 21881303
TI  - Mass spectrometry-based quantitative analysis and biomarker discovery.
AB  - Mass spectrometry-based quantitative analysis and biomarker discovery using
      metabolomics approach represent one of the major platforms in clinical fields
      including for the prognosis or diagnosis, assessment of severity and response to
      therapy in a number of clinical disease states as well as therapeutic drug
      monitoring (TDM). This review first summarizes our mass spectrometry-based
      research strategy and some results on relationship between cysteinyl leukotriene
      (cysLT), thromboxane (TX), 12-hydroxyeicosatetraenoic acid (12-HETE) and other
      metabolites of arachidonic acid and diseases such as atopic dermatitis,
      rheumatoid arthritis and diabetes mellitus. For the purpose of evaluating the
      role of these metabolites of arachidonic acid in disease status, we have
      developed sensitive determination methods with simple solid-phase extraction and
      applied in clinical settings. In addition to these endogenous compounds, using
      mass spectrometry, we have developed actually applicable quantitative methods for
      TDM. Representative example was a method of TDM for sirolimus, one of the
      immunosuppressant agents for a recipient of organ transplant, which requires
      rigorous monitoring of blood level. As we recognized great potential in mass
      spectrometry during these researches, we have become interested in metabolomics
      as the non-targeted analysis of metabolites. Now, established strategy for the
      metabolomics investigation applies to samples from cells, animals and humans to
      separate groups based on altered patterns of metabolites in biological fluids and
      to identify metabolites as potential biomarkers discriminating groups. We would
      be honored if our research using mass spectrometry would contribute to provide
      useful information in the field of medical pharmacy.

PMID- 21881304
TI  - Functional glutamate signaling in neural progenitor cells.
AB  - In this review, we have summarized our recent studies on the functionality of
      ionotropic (iGluR) and metabotropic (mGluR) glutamate receptors expressed by
      undifferentiated neural progenitor cells (NPC) isolated from embryonic rat and
      mouse brains. NPC are primitive cells with the self-renewal capacity as well as
      the multipotentiality to generate different neural lineages including neurons,
      astrocytes, and oligodendrocytes. Isolated cells were cultured in the presence of
      growth factors for the formation of round spheres by clustered cells so-called
      'neurospheres' under floating conditions. Reverse transcription polymerase chain
      reaction analyses revealed expression of mRNA for particular iGluR and mGluR
      subtypes in NPC. Moreover, sustained exposure to an agonist for the N-methyl-D
      aspartate receptor (NMDAR) not only inhibited the formation of neurospheres but
      also promoted differentiation of NPC into cells immunoreactive to a neuronal
      marker protein on immunocytochemistry and western blot analyses. On the other
      hand, sustained exposure to an agonist for the group III mGluR subtype led to
      suppression of proliferation activity in these neurospheres along with
      facilitation of the subsequent differentiation into astrocytes. Accordingly,
      glutamate could play a pivotal role in the mechanisms underlying proliferation
      for self-replication, together with determination of the subsequent
      differentiation fate toward particular progeny lineages through activation of
      NMDAR and group III mGluR subtypes in NPC.

PMID- 21881305
TI  - Effect of environmental factor influencing the development of mouse cerebral
      cortex.
AB  - The cerebral cortex is organized into six cell layers, each of which contains
      neurons with similar morphology, functions, gene-expression profiles, and
      projection patterns. These layer-specific neuronal phenotypes are sequentially
      generated from common cortical progenitor cells in the ventricular zone of dorsal
      telencephalon. Although recent investigations have clarified important roles of
      intrinsic factors such as transcription factors and regulators of the cell cycle
      for the maturation of cortical progenitors, growth factors and neurotrophic
      factors environmentally supplied by the cerebral cortex are thought to regulate
      proliferation and neural development and determine neuronal differentiation in
      the cerebral cortex. In this review, I focus on the function of neurotrophin
      family neurotrophic factor, including nerve growth factor, brain-derived
      neurotrophic factor (BDNF), neurotropin-3 (NT-3) and neurotrophin-4 in the
      formation of the neuronal layer of the cerebral cortex. Especially, BDNF and NT-3
      are expressed in the proliferating cortical progenitors and influence the
      biological properties of cortical progenitors prior to neurogenesis and play
      distinct roles in generation of cortical neuronal subtypes.

PMID- 21881306
TI  - Novel iodocyclization method based on the controlling of oxidative aromatization.
AB  - We have developed a new method of iodocyclization based on reagent-controlled
      oxidative aromatization. Our strategy takes advantage of the dual nature of
      iodine as both an iodinating and an oxidizing agent. This approach enabled
      "product switch" and enhanced the flexibility of the synthetic pathway toward
      pyrazoles and isoxazoles. In addition, the iodo moiety of the cyclized product
      could create further diversity. The utility of our methodology was demonstrated
      in the synthesis of valdecoxib and its 2,5-dihydro analogs.

PMID- 21881307
TI  - Molecular regulation of muscle stem cells by 'quiescence genes'.
AB  - Skeletal muscle has great regenerative potential that depends on muscle stem
      cells, called satellite cells. In uninjured muscle, satellite cells reside
      beneath the basal lamina and are maintained in quiescent and undifferentiated
      state. This state is considered a requisite for sustaining the satellite cell
      pool, but the molecular mechanism is still unknown. In our previous study, we
      developed a novel monoclonal antibody that specifically recognized muscle
      satellite cells in skeletal muscle. Using this monoclonal antibody, we purified
      satellite cells and performed genome-wide transcriptome analysis. In these
      analyses, we found that satellite cells expressed Hesr1/Hey1 and Hesr3/HeyL genes
      known as down stream target of Notch signaling. Although each single knock out
      mice did not indicate obvious phenotype in skeletal muscle, Hesr1/Hesr3 double
      knock out mice showed remarkably decreased number of satellite cells.
      Intriguingly, dKO satellite cells were not kept in quiescent and differentiated
      state in adult skeletal muscle. This dysregulated state of satellite cells lead
      to gradually decreased number of satellite cells and age-dependent regeneration
      defect. These results indicate that Hesr1/3 is essential for muscle stem cell
      biology and will facilitate this research field.

PMID- 21881309
TI  - Metal-free direct biaryl coupling reaction of heteroaromatic compounds via
      iodonium intermediate.
AB  - Biaryl compounds are versatile building blocks in the synthesis of natural
      products, pharmaceuticals, agricultural chemicals and pi-conjugated organic
      materials. This review describes a recent progress for the biaryl cross-coupling
      reaction of heteroaromatic compounds using hypervalent iodine reagent. Our novel
      biaryl coupling reaction is a unique method for constructing various
      heteroaromatic biaryls without use of transition metal catalysts. From
      mechanistic point of view, the coupling reaction was realized through stable
      iodine intermediate generated from heteroaroamatic compound and iodine (III)
      reagent.

PMID- 21881308
TI  - Optimization of adenovirus vectors for transduction in embryonic stem cells and
      induced pluripotent stem cells.
AB  - Because embryonic stem (ES) cells and induced pluripotent stem (iPS) cells can
      differentiate into various types of cells in vitro, they are considered as a
      valuable model to understand the processes involved in the differentiation into
      functional cells as well as an unlimited source of cells for therapeutic
      applications. Efficient gene transduction method is one of the powerful tools for
      the basic researches and for differentiating ES and iPS cells into lineage
      committed cells. Recently, we have developed an adenovirus (Ad) vector for
      efficient transduction into ES and iPS cells. We showed that Ad vectors
      containing the cytomegalovirus enhancer/beta-actin promoter with beta-actin
      intron (CA) promoter or the elongation factor (EF)-1alpha promoter were the
      appropriate for the transduction into ES and iPS cells. We also found that
      enforced expression of a PPARgamma gene or a Runx2 gene into mouse ES and iPS
      cells by an optimized Ad vector markedly augmented the differentiation of
      adipocytes or osteoblasts, respectively. Thus, a gene transfer technique using an
      Ad vector could be an advantage for the regulation of stem cell differentiation
      and could be applied to regenerative medicine based on ES and iPS cells.

PMID- 21881310
TI  - Drug discovery for improvement of chronic kidney disease and cardiovascular
      disease.
AB  - Chronic kidney disease (CKD) has been increasingly recognized as a major public
      health problem in the world. Recent studies have showed that CKD is an
      independent risk factor for the occurrence of cardiovascular disease (CVD).
      Reactive oxygen species (ROS), generated by reduction-oxidation actions, have
      been generated by reduction-oxidation actions, recognized as the important
      chemical mediators that regulate signal transduction in various cells including
      vascular smooth muscle cells (VSMC) and mesangial cells (MC). It has been showed
      that increase in ROS generation may relate to a risk for CVD and CKD. In
      addition, ROS mediate activation of mitogen-activated protein (MAP) kinases,
      extracellular signal-regulated kinase 1/2, c-Jun N-terminal kinase, p38, and big
      MAP kinase 1, in various cells leading to change in gene expressions. Control of
      the oxidative stress and ROS-mediated alterations of signaling molecules
      including MAP kinases may provide new therapeutic strategy against CKD and CVD.
      In this review, we summarize mainly our data regarding the pharmacological
      effects of renin-angiotensin-aldosterone system blockers, bioflavonoids and
      adiponectin in VSMC and MC. Also we review the data on a possible new class drug
      against oxidative stress to improve CKD and CVD.

PMID- 21881311
TI  - Development of an online incident-reporting system for management of medical
      risks at hospital.
AB  - To minimize their occurrence, it is important to gather and analyze data
      regarding cases of not only medical accidents but also of incidents involving
      potential harm to patients. In gathering data, we have separated reporting
      between the details of such incidents and information about their occurrence. We
      have implemented a system involving a first report to achieve prompt notification
      and a second report to provide details. An online report input system has been
      established taking into consideration both ease of input and promptness of
      information sharing. We discuss the input of the first and second reports in a
      total of 951 cases over a period of 6 months. From the data regarding the timing
      of the first report, 307 and 789 cases were reported within 24 h and 48 h,
      respectively, indicating that the first report was input mostly without delay in
      accordance with the operational guidelines. On the other hand, it took 14 days to
      surpass a second report rate of 80%. Cases that took more than 2 weeks to be
      reported would likely have gone unreported had there not been a first report to
      indicate and confirm that an incident had even occurred. Investigation is needed,
      especially for problematic cases, so we assume that discovering important
      incidents via the first report has been successful. In addition, details of
      incidents can be input into this system in free-text, yielding information that
      cannot be acquired with multiple choice input as in standard reporting systems.

PMID- 21881312
TI  - Evaluation of brilliance and visibility of fluorescence and chemiluminescence
      solution for training of preparing injections.
AB  - Personnel who prepare and administer chemotherapeutic agents have been reported
      to develop untoward effects. The use of appropriate techniques for preparing
      these agents is encouraged, and educational training systems that involve the use
      of a fluorescent or chemiluminescence reagent as placebos have been established
      to minimize potential exposure to these agents. However, the optimum conditions
      for the use and visibility of these placebos remain obscure. In this study, our
      results indicated that the fluorescence intensity of fluorescent reagent
      decreased when it was used at a concentration greater than 0.01%. Because drops
      created due to splashes and leaks are extremely small and easily evaporate, it is
      possible that the fluorescence resulting from such drops readily disappears
      despite using an anti-evaporation reagent. We also developed a method to evaluate
      the visibility of the small drop; using this method, we determined the distance
      at which the drop present on the pin could be seen by the observer. The distance
      at which the drop was clearly recognized as a pinpoint by using the fluorescence
      method was almost comparable to that for the chemiluminescence method. In the
      chemiluminescence method, the drop on the pin was faintly visible as a slightly
      bright area because of low background when observed at a certain distance that
      was much greater than that at which the drop was clearly visible; however, such
      an area was not observed in the fluorescence method. The results of our study
      will help in the selection of a training method depending on the situation.

PMID- 21881313
TI  - Effects of implementation of problem-based learning tutorials on fifth-year
      pharmacy students and future issues.
AB  - At Tohoku Pharmaceutical University, problem-based learning (PBL) tutorials were
      incorporated into "prescription analysis" and "case analysis" for fifth-year
      students in 2010 with the following objectives: 1 application and confirmation of
      acquired knowledge and skills, and acquisition of 2 communication ability, 3
      presentation ability, 4 cooperativeness through groupwork, and 5 information
      collecting ability. In the present study, we conducted a questionnaire survey on
      a total of 158 fifth-year students in order to investigate the educational
      benefits of PBL tutorials. The results showed that the above five objectives of
      PBL tutorials were being achieved, and confirmed the educational benefits
      expected of PBL tutorials. In contrast, it was found to be necessary to improve
      the contents of scenarios and lectures, time allocation regarding schedules, the
      learning environment, the role of tutors, and other matters. In order to maximize
      the educational benefits of PBL tutorials, it will be necessary in the future to
      continue to conduct surveys on students and make improvements to the curriculum
      based on survey results.

PMID- 21881314
TI  - Induction of caspase-3-dependent apoptosis in human leukemia HL-60 cells by delta
      elemene.
AB  - delta-Elemene, an antitumor component, is a chemical compound isolated from
      Curcuma wenyujin, a Chinese traditional herb. We examined whether delta-elemene
      could inhibit cell growth and cell cycle progression and induce apoptosis in
      human leukemia HL-60 cells. The results demonstrated that delta-elemene induces
      significant apoptosis of HL-60 cells, as shown by MTT assay, annexin V (AnV)
      binding of externalized phosphatidylserine (PS), and the mitochondrial probe JC-1
      using flow cytometry. HL-60 cells treated with delta-elemene showed high
      percentages in the early apoptotic and late apoptoctic/necrotic stages, as well
      as caspase-3 activation of HL-60 cells. By monitoring the changes in cell cycle
      profiles, we confirmed that delta-elemene could interfere with the cell cycle in
      the G2/M phase and induce apoptosis in HL-60 cells in a time-dependent manner.
      Caspase-3 plays a direct role in proteolytic cleavage of the cellular proteins
      responsible for progression to apoptosis. Therefore we examined apoptosis in HL
      60 cells after exposure to delta-elemene and measured caspase-3 activities with
      or without Z-Val-Ala-Asp-fluoromethylketone (z-VAD-fmk, a broad-spectrum caspase
      inhibitor) pretreatment using flow cytometric analysis. The results showed that
      delta-elemene could induce caspase-3 activation as detected by the decrease in
      delta-elemene-induced caspase-3 activities after treatment with z-VAD-fmk. In the
      present study, delta-elemene activated typical caspase-dependent apoptosis in HL
      60 cells, as demonstrated by an inhibitory effect of z-VAD-fmk on this cell
      death. During delta-elemene-induced apoptosis, cytochrome c and apoptosis
      inducing factor were released into the cytosol and BAX was translocated from the
      cytosol to mitochondria. However, these were not prevented by z-VAD-fmk. In
      conclusion, our study demonstrated that delta-elemene could induce G2/M cell
      cycle transition and trigger apoptosis through a caspase-3-dependent pathway.

PMID- 21881315
TI  - Effect of hemopurification rate on doripenem pharmacokinetics in critically ill
      patients receiving high-flow continuous hemodiafiltration.
AB  - Hemopurification is an effective therapy for acute kidney injury, defined as
      creatinine clearance less than 30 ml/min, which occurs frequently in the
      intensive care unit. These critically ill patients often have severe infectious
      complications and are thus often treated with antibiotics. However, the effect of
      hemopurification on the pharmacokinetics of antibiotics is not well understood.
      In this study, we investigated the pharmacokinetics of doripenem (DRPM) in
      critically ill patients with accompanying renal dysfunction undergoing continuous
      hemodiafiltration by high-volume filtration/high-flow dialysis (high-flow CHDF)
      and compared it to the pharmacokinetics of DRPM during conventional CHDF. We
      studied 8 patients (2 in the high-flow group and 6 in the conventional group) in
      whom DRPM was administered while performing CHDF for acute kidney injury. DRPM
      (250 mg) was intravenously infused over 1 h. For the conventional group, CHDF was
      performed at a blood flow rate (Q(B)) of 100 ml/min, dialysate flow rate (Q(D))
      of 500 ml/h, and filtration flow rate (Q(F)) of 300 ml/h. For the high-flow
      group, CHDF was performed at a blood flow rate (Q(B)) of 100 ml/min, dialysate
      flow rate (Q(D)) of 1500 ml/h, and filtration flow rate (Q(F)) of 900 ml/h. For
      both groups, a polysulfonehemofilter with a membrane area of 1.0 m(2) was used.
      Mean half-life, total body clearance, and clearance via hemodiafiltration of DRPM
      were 2.9 h, 118 ml/min, and 41.9 ml/min, respectively, in the high-flow group,
      and 7.9 h, 58 ml/min, and 13.5 ml/min in the conventional group. Clearance via
      hemodiafiltration increased approximately 3-fold by tripling the hemopurification
      rate. Therefore, CHDF parameters greatly affected DRPM pharmacokinetics in
      patients receiving CHDF. These results suggest that clearance via
      hemodiafiltration increases proportionally to the hemopurification rate. Thus, it
      is reasonable to conclude that DRPM dose must be increased to 1.0-1.5 g/day when
      performing high-flow CHDF.

PMID- 21881316
TI  - Reflecting the thoracic fellowship in Canada as a Japanese thoracic surgeon: is
      there anything we should follow?
AB  - In Japanese surgical society, there have been urgent discussions as to the
      decrease in the number of junior doctors who want to be surgical specialists.
      This problem seems to have originated from the loss of attractiveness of surgery.
      One of the counter-measures to regain the attractiveness of surgical specialties
      might be a well-organized training system, for which the Japanese Board of
      General Thoracic Surgery (JBGTS), as well as those of other surgical
      subspecialties, has struggled. Fortunately, I had an opportunity of general
      thoracic surgery training in Canada, and had a chance to reflect on the thoracic
      training programs of both countries. Based on my experience as a thoracic fellow
      in Canada, I would like to introduce the Canadian way of thoracic surgery
      training, referring to the differences between each program.

PMID- 21881317
TI  - Valve-sparing aortic root replacement.
AB  - The aortic root has a unique 3-dimensional configuration and the distinctive
      function of supporting the aortic valve and blood vessels. The sinuses of
      Valsalva are crucial to create appropriate eddy currents that are important in
      initiating and coordinating aortic valve closure and promoting coronary artery
      blood flow. Most aneurysms in the aortic root are associated with degenerative
      changes in the elastic media rather than atherosclerosis. Valve-sparing root
      repair has become widely accepted, although the Bentall procedure remains the
      gold standard. Because reimplantation using the Valsalva graft allows root
      geometry to be retained and theoretically and practically prevents recurrent
      aortic valve regurgitation, it is considered the most reliable and preferred
      technique among various valve-sparing aortic root repair procedures.

PMID- 21881318
TI  - Extended thymectomy via videothoracoscopy-assisted stepwise-access sternotomy.
AB  - A method of videothoracoscopy-assisted extended thymectomy procedure performed
      through a movable small access window is introduced. The access window can be
      moved stepwise and longitudinally alongside full sternotomy to be upon the
      dissection site. The majority of the thymectomy procedure can be directly viewed
      and operated from the moving window. However, partial and complete thoracoscopic
      maneuvers are required for dissection of the lateral-most region near the phrenic
      nerve and the upper poles of the thymus, respectively.

PMID- 21881319
TI  - Ki-67 labeling index is associated with recurrence after segmentectomy under
      video-assisted thoracoscopic surgery in stage I non-small cell lung cancer.
AB  - OBJECTIVES: Video-assisted thoracoscopic surgery (VATS) segmentectomy for small
      or early stage non-small cell lung cancer (NSCLC) remains controversial. Here, we
      investigated the clinical importance of predicting recurrence by Ki-67 in VATS
      segmentectomy for stage I NSCLC. METHODS: In a retrospective study, 44
      consecutive patients in p-stage I underwent VATS segmentectomy between September
      2003 and April 2009. After clinicopathological factors were compared with Ki-67
      expression, the relationship between Ki-67 labeling indexes (LI) or mRNA
      expression by quantitative RT-PCR and prognosis was investigated. RESULTS: Five
      of 44 VATS segmentectomy patients relapsed. In the relapsed patients, 3 (6.8%)
      were local recurrences and 2 (4.5%) were distant metastases. There was no
      significant difference between clinicopathological factors and recurrence;
      however, patients with Ki-67 LI less than 5% showed better disease-free survival
      than patients with Ki-67 LI over 5% (p = 0.04). In multivariate Cox regression
      analysis, although there was no significantly different in disease-free survival
      by age, histology, tumor size, only Ki-67 LI showed a significant prognostic
      factor of recurrence (HR = 12.5, 95% CI = [1.1-1407], p = 0.04). CONCLUSIONS: Ki
      67 LI after VATS segmentectomy was a prognostic factor of disease-free survival
      in NSCLC and the treatment of choice for patients with positive LI may be
      considered, in addition to adjuvant chemotherapy, or lobectomy.

PMID- 21881320
TI  - Complex reconstruction of supraaortic branches.
AB  - OBJECTIVE: The present paper exemplary describes several severe stenoses of
      supraaortic branches with its symptoms and operative treatments. METHODS: Eight
      patients, two female (68 +/- 5 y), six male (73 +/- 4 y), were retrospectively
      evaluated. Patients showed neurological signs as followed: recurring attacks of
      vertigo (80%), temporary paresis of extremity (20%), speech disorders (20%) and
      subclavian and/or carotic-steel-syndrome (15%). Seven patients have already been
      previously treated with revascularization of the supraaortic branches in the
      past. The surgical techniques used were thrombendarterectomy of the internal
      carotid artery, carotid-subclavian bypass and complex aorto-truncal, aorto
      carotid and aorto-subclavian-bypass. RESULTS: One patient died nine days
      postoperatively due to myocardial infarction. Mean duration of stay on intensive
      care unit was 1.5 days. Mean duration of postoperative ventilation was six hours.
      Average duration of stay on normal ward was nine days. CONCLUSION: This study
      presents several complex reconstructions of supraaortic branches, which were
      indicated in cases with severe stenoses of supraaortic branches. Even though
      treatment strategies were complex the peri- and postoperative complication rates
      are quite low. These therapeutic strategies were necessary to avoid severe
      neurological complications in these patients.

PMID- 21881322
TI  - Mid-term results for the Maze procedure in patients with non-mitral valvular
      atrial fibrillation.
AB  - BACKGROUND: The Maze procedure in patients without mitral valve disease remains
      controversial, because of the increased invasiveness and operation time required
      to create additional incisions in the atria. The aim of this study was to assess
      prognosis following the Maze procedure in patients without mitral valve disease.
      METHODS AND RESULTS: One hundred and seven consecutive patients who underwent the
      Maze procedure between 2002 and 2008 was enrolled in this study. Patients were
      divided into two groups based on the presence or absence of mitral valve disease.
      Freedom from atrial fibrillation was compared by multivariate logistic regression
      analysis at discharge. The Kaplan-Meier method and Cox-proportional hazard
      analysis adjusted for other predictors were estimated to compare freedom from
      atrial fibrillation at follow-up. Follow-up was 98% complete and mean duration of
      follow-up was 457 days. Operation and aorta cross-clamp times were similar
      between groups. No differences were identified in freedom from atrial
      fibrillation at discharge (non-mitral valve surgery, 55% vs. mitral valve
      surgery, 66%) or follow-up (57% vs. 61%, respectively). In multivariate Cox
      proportional hazard modelling, the presence of mitral valve disease was not
      associated with a poor success rate of conversion. CONCLUSIONS: Results of the
      Maze procedure for atrial fibrillation without mitral valve disease were
      acceptable. The Maze procedure could be a beneficial option for these patients to
      avoid adverse events of atrial fibrillation.

PMID- 21881321
TI  - Zero mortality of continuous veno-venous hemodiafiltration with PMMA hemofilter
      after pediatric cardiac surgery.
AB  - OBJECTIVE: Continuous veno-venous hemodiafiltration (CVVH) is used as one of the
      modalities of continuous renal replacement therapy (CRRT) in pediatric intensive
      units. The aim of our study was to investigate the use of CVVH in small children
      with acute renal failure (ARF) after cardiac surgery. PATIENT AND METHODS:
      Between June 2005 and June 2008, 7 patients who required dialysis after pediatric
      cardiac surgery without ECMO underwent CVVH with polymethylmethacrylate membrane
      (PMMA) treatment. The definition of ARF was based on a 100% rise in serum
      creatinine (Cr) concentration, oliguria. On the other hand, PMMA-CVVH was weaned
      in patients with satisfactory urine output, stable biochemical markers of renal
      function and adequate fluid balance. RESULTS: All patients treated with PMMA-CVVH
      alone (4 boys, 3 girls) had a median age of 36 months and a median body weight of
      11 kg. The averaged established time from cardiac operation to CVVH was 2.6 days.
      There was a significant decrease in the post-filter compared with pre-filter
      levels of BUN, Cr, potassium concentration. There were no significant changes in
      systolic blood pressure, lactate level and CRP; however, it was unnecessary for
      all patients to use epinephrine. CONCLUSIONS: Continuous veno-venous
      hemodiafiltration with PMMA-CVVH without ECMO achieved a surprisingly Zero
      mortality.

PMID- 21881323
TI  - Low-dose atrial natriuretic peptide for chronic kidney disease in coronary
      surgery.
AB  - PURPOSE: Chronic kidney disease (CKD) is an independent risk factor for
      cardiovascular disease. We investigated the effectiveness of human atrial
      natriuretic peptide (hANP) infusion in CKD patients undergoing coronary artery
      bypass grafting (CABG). PATIENTS AND METHODS: We analyzed 134 consecutive cases
      in which CABG had been performed in our hospital from 2002 to 2005. They were
      divided into four groups: Group A (n = 19) was CKD + placebo, Group B (n = 30)
      was non-CKD + placebo, Group C (n = 22) was CKD + hANP, and Group D (n = 63) was
      non-CKD + hANP). The serum creatinine (mg/dl) and estimated glomerular filtration
      rate (ml/min/1.73 m2) were measured as evaluation values. RESULTS: The value of
      sCr changed preoperatively and at 1 year postoperatively from 1.09 +/- 0.09, 51.3
      +/- 4.4 to 1.26 +/- 0.42, 49.4 +/- 14.4 in Group A, from 0.77 +/- 0.14, 75.5 +/-
      12.1 to 0.91 +/- 0.40, 72.3 +/- 19.5 in Group B, from 0.99 +/- 0.12, 54.8 +/- 3.0
      to 0.93 +/- 0.16, 64.2 +/- 12.3 in Group C and from 0.77 +/- 0.13, 77.7 +/- 13.4
      to 0.83 +/- 0.17, 75.9 +/- 16.2 in Group D, respectively. There was a significant
      difference between Group A and Group C regarding the change of creatinine (p
      =0.0022). CONCLUSION: Our study has confirmed that an infusion of hANP during
      CABG in patients with CKD not only improves perioperative renal function, but
      also prevents the progression of CKD.

PMID- 21881324
TI  - The effect of sivelestat sodium hydrate on severe respiratory failure after
      thoracic aortic surgery with deep hypothermia.
AB  - Patients who undergo thoracic aortic surgery with deep hypothermia frequently
      have postoperative respiratory failure as a complication. Severe lung injury in
      these patients results in a fatal outcome. A specific neutrophil elastase
      inhibitor, sivelestat sodium hydrate, is an innovative therapeutic drug for acute
      lung injury. We evaluated the protective effects of sivelestat sodium hydrate on
      severe lung injury after thoracic aortic surgery with deep hypothermia. From
      January 2002 to July 2007, 71 consecutive patients underwent thoracic aortic
      surgery with deep hypothermia. Of these patients, 22 had postoperative
      respiratory failure with PaO2/FiO2 ratios of less than 150. They were randomly
      assigned to one of two groups. The first group (Group S, n = 10) was administered
      sivelestat sodium hydrate continuously at 0.2 mg/kg/h until weaning from
      mechanical ventilation; the second group (Group C, n = 12) was not administered
      sivelestat sodium hydrate. The groups were comparable with respect to clinical
      data. There were no significant differences between the two groups in age,
      operation duration, total cardiopulmonary bypass time, circulatory ischemia time,
      cardiac arrest time, intraoperative blood loss, and total transfusion volume. The
      improvement of pulmonary function was observed in the both groups, but more
      marked in Group S by statistical analysis using analysis of variance for repeated
      measurements. Especially, in the early phase, pulmonary function improvement was
      more marked in Group S. The duration of mechanical ventilation, the length of
      stay in the intensive care unit, and the length of hospital stay were shorter in
      Group S, but not significantly. Sivelestat sodium hydrate is a specific
      neutrophil elastase inhibitor that improves pulmonary function in patients with
      severe postoperative respiratory failure following thoracic aortic surgery with
      deep hypothermia. The drug may shorten the duration of postoperative ventilation,
      intensive care unit stay, and hospital stay.

PMID- 21881325
TI  - Do preoperative statins reduce atrial fibrillation after coronary artery bypass
      grafting?
AB  - OBJECTIVE: Recent studies have demonstrated that statins have pleiotropic
      effects, including anti-inflammatory effects and atrial fibrillation (AF)
      preventive effects. The objective of this study was to assess the efficacy of
      preoperative statin therapy in preventing AF after coronary artery bypass
      grafting (CABG). METHODS: 221 patients underwent CABG in our hospital from 2004
      to 2007. 14 patients with preoperative AF and 4 patients with concomitant valve
      surgery were excluded from this study. Patients were divided into two groups to
      examine the influence of statins: those with preoperative statin therapy (Statin
      group, n = 77) and those without it (Non-statin group, n = 126). In addition,
      patients were divided into two groups to determine the independent predictors for
      postoperative AF: those with postoperative AF (AF group, n = 54) and those
      without it (Non-AF group, n = 149). Patient data were collected and analyzed
      retrospectively. RESULTS: The overall incidence of postoperative AF was 26%.
      Postoperative AF was significantly lower in the Statin group compared with the
      Non-statin group (16% versus 33%, p = 0.005). Multivariate analysis demonstrated
      that independent predictors of AF development after CABG were preoperative statin
      therapy (odds ratio [OR] 0.327, 95% confidence interval [CI] 0.107 to 0.998, p =
      0.05) and age (OR 1.058, 95% CI 1.004 to 1.116, p = 0.035). CONCLUSION: Our study
      indicated that preoperative statin therapy seems to reduce AF development after
      CABG.

PMID- 21881326
TI  - Encouraging experience with intracardiac transplantation of unselected autologous
      bone marrow cells concomitant with coronary artery bypass surgery after
      myocardial infarction.
AB  - BACKGROUND: Chronic heart failure after myocardial infarction is still a serious
      problem without a fundamental therapy. Experimental transplantation of bone
      marrow cells (BMC) into infarcted myocardium resulted in regeneration and
      functional improvement. OBJECTIVE: Clinical investigation of safety and efficacy
      of intracardiac transplantation of unselected autologous BMC. METHOD: 22 patients
      scheduled for elective and isolated coronary artery bypass grafting (CABG) with a
      reduced LVEF due to myocardial infarction were included. Intraoperatively,
      sternal bone marrow blood was aspirated, and a sterile buffy coat was prepared
      and applicated. 19 age, LVEF and coronary disease matched patients served as
      controls. Heart function, geometry, and scar proportion were assessed by
      echocardiography and Gadolinium-MRI at the time of the operation and 6 months
      thereafter. RESULTS: Transplanted patients received a mean number of 360 * 106
      BMC. We did not notice any significant differences in early or late complications
      in the transplant group as compared to controls. At six months follow up only the
      transplanted patients showed a significant improvement of NYHA classes from 2.7
      to 1.5 and of LVEF from 36 to 43 %, (p < 0.05). Furthermore, only CABG
      concomitant with BMC-TX led to a significant reduction of left ventricular end
      diastolic diameter (LVEDD) from 59 to 54 mm and of scar proportion of the
      infarcted segments from 2.53 to 2.42, (p < 0.05). CONCLUSION: Intracardiac
      transplantation of unselected, autologous BMC is safe and feasible. In adjunct
      with coronary revascularization it leads to an improvement of ventricular
      geometry and function. Moreover, it reduces myocardial scar proportion and heart
      failure symptoms.

PMID- 21881327
TI  - Adalimumab-associated pulmonary cryptococcosis.
AB  - This is the first report of adalimumab-associated pulmonary cryptococcosis. A 56
      year-old female with rheumatoid arthritis without a history of pulmonary disease
      was simultaneously administered adalimumab (40 mg/2 wks), methotrexate (4 mg/wk),
      and isoniazid (200 mg/day). Five months later, chest radiography revealed a small
      spiculated pulmonary nodule, and the laboratory test results, including levels of
      tumor markers and plasma beta-D-glucan, were within normal ranges. Since the
      lesion continued to grow, even after discontinuing adalimumab, it was surgically
      resected. Grocott staining of the tissue sample revealed black-brown fungi,
      identified as Cryptococcus neoformans in culture. The patient now remains well,
      without adalimumab therapy.

PMID- 21881328
TI  - Preferred surgical approach for dumbbell-shaped tumors in the posterior
      mediastinum.
AB  - We present the case of a 67-year-old male smoker with a posterior mediastinal
      hemangioma. Radiological findings revealed a dumbbell-shaped tumor with a
      neuroforaminal extension in the right paravertebral space. Under the preoperative
      diagnosis of a neurogenic tumor, surgery was performed using a combined anterior
      and posterior approach. During the thoracotomy, the tumor was found to be a
      hemangioma. We ligated the involved vessels before performing laminectomy, thus
      ensuring that complete tumor resection was achieved without massive bleeding in
      the spinal canal. Dumbbell-shaped hemangiomas are rare, and preoperative
      confirmation of the diagnosis is challenging. Thoracotomy before laminectomy is
      optimal for the resection of dumbbell-shaped tumors of the mediastinum,
      especially with marked vascularity, given that the initial thoracotomy procedures
      facilitate the subsequent laminectomy procedures.

PMID- 21881329
TI  - Extra-corporeal membrane oxygenation in a patient with Fusobacterium sepsis: a
      case report and review of literature.
AB  - An adolescent female was admitted to the pediatric intensive care unit in septic
      shock. She developed multisystem organ dysfunction including pancreatitis with
      myocardial dysfunction and hemodynamic instability unresponsive to medical
      management necessitating veno-arterial extracorporeal support. Streptococcus
      Constellata and Fusobacterium necrophorum were isolated from blood cultures. This
      is the first report of extra-corporeal cardiac support in fusobacterium sepsis.

PMID- 21881330
TI  - Giant solitary fibrous tumour of pleura -an uncommon intrathoracic entity- a case
      report and review of the literature.
AB  - A 43-year-old woman presented to us with progressive breathlessness, dry cough
      and weight loss. A chest radiograph showed homogeneous opacification of the
      entire left hemithorax. A contrast enhanced computed tomography (CECT) scan of
      the thorax showed a large intrathoracic mass occupying almost the entire left
      hemithorax and appeared grossly inoperable. A transcutaneous CT guided tru-cut
      biopsy revealed a solitary fibrous tumour. We reviewed the CT scans based on the
      biopsy report, and, in retrospect, the mediastinal vessels seemed more stretched
      and pushed by the tumor rather than directly infiltrated by it. We performed an
      exploratory thoracotomy and to our surprise, were able to dissect the mass quite
      easily off the mediastinum. She had an uneventful postoperative recovery, and the
      final histopathology confirmed a solitary fibrous tumor. We report this case to
      emphasize that a cursory clinico-radiological interpretation can dissuade
      surgical intervention in these patients.

PMID- 21881332
TI  - A case of sclerosing hemangioma forming a pedunculated mass.
AB  - We report our experience with an unusual case of sclerosing hemangioma (SH) that
      formed a pedunculated mass protruding into the thoracic cavity. A pulmonary tumor
      was found in a 60-year-old female during the medical examination. Computed
      tomography showed a 19 * 17-mm nodule with a clear border and smooth margin
      contiguous with the diaphragm in the right S8 segment. Uneven enhancement
      following contrast medium administration was observed. We performed a 3-port
      thoracoscopic wedge resection of the right lower lobe. We observed a yellow
      pedunculated tumor protruding from the diaphragmatic surface of the right lower
      lobe. The surface of the tumor was smooth and encapsulated. Microscopically, we
      diagnosed it as a SH. SHs usually exist adjacent to the visceral pleura, but
      rarely form pedunculated tumors protruding into the cavity as seen in this case.
      By thoracoscopic surgery, we successfully diagnosed and treated the patient in a
      minimally invasive manner. Since there have been reported cases of recurrence, we
      anticipate that periodic follow-up observations will be required.

PMID- 21881331
TI  - Solitary pulmonary metastasis from carcinoma of the papilla of vater.
AB  - Pulmonary metastasis from carcinoma of the papilla of Vater is considered to be a
      late event, and patients can be treated with radiotherapy, chemotherapy, or
      palliative surgery. However, surgical treatment of an isolated lung metastasis
      has not been reported. We present a surgical case of solitary pulmonary
      metastasis from carcinoma of the papilla of Vater. A 51-year-old man underwent
      pylorus-preserving pancreaticoduodenectomy for Vater carcinoma. During follow-up,
      chest computed tomography revealed a nodular shadow in the right lung. The
      pathological examination demonstrated the appearance of the pulmonary tumor
      resembled that of the previously resected Vater carcinoma, and both tumors showed
      similar immunostaining properties, leading to the pathological diagnosis of
      pulmonary metastasis from carcinoma of the papilla of Vater. Isolated pulmonary
      metastasis from carcinoma of the papilla of Vater is extremely rare, but surgery
      could be the treatment of choice.

PMID- 21881333
TI  - Left atrial intramural hematoma after resection of myxoma: report of a case.
AB  - A 73-year-old woman was referred for treatment of left atrial (LA) myxoma. At
      surgery, a myxoma was attached to the left atrial side of the fossa ovalis in the
      atrial septum by a stalk and was transmurally excised with a margin of the atrial
      septum. The atrial septum was closed without any prosthetic materials under mild
      to moderate tension. Although she was asymptomatic, postoperative transesophageal
      echocardiography (TEE) revealed an abnormal cavity, containing heterogeneous
      echogenesity without blood flow, in the posterior LA wall. Magnetic resonance
      imaging (MRI) demonstrated a mass without significant enhancement. It was
      considered to be an intramural hematoma, and the diagnosis of LA dissection was
      made. Follow-up echocardiography showed disappearance of the dissected lumen
      without surgical intervention. Both TEE and MRI are useful for the correct
      diagnosis of an LA dissection; and surgical intervention, entry closure or
      internal drainage, may not always be necessary in the absence of a hemodynamic
      compromise with an LA dissection.

PMID- 21881334
TI  - Septic embolic occlusion of the superior mesenteric artery induced by mitral
      valve endocarditis.
AB  - A 75-year-old woman, who had been treated for rheumatic arthritis, was
      transferred to our hospital because of acute abdomen and continuous fever for
      several weeks. She had peritonitis, and abdominal computed tomography detected a
      thrombus occluding the proximal superior mesenteric artery and infarctions of the
      kidneys and spleen. Echocardiography showed a large vegetation on the anterior
      leaflet of the mitral valve. The necrotic small bowel and ascending colon were
      resected, and mitral valve replacement was performed 5 days later. She suffered
      from hyperbilirubinemia and pneumonia for several weeks after the operation but
      recovered successfully thereafter.

PMID- 21881335
TI  - Quadricuspid aortic valve with ascending aortic aneurysm: a case report and
      histopathological investigation.
AB  - We describe the case of a 69 year-old woman with a dilated ascending aorta, who
      presented with aortic valve regurgitation due to a quadricuspid aortic valve
      (QAV). There are only a few reports in the literature describing aortic
      replacement and subsequent aortic valve replacement for a malfunctioning QAV. We
      discuss the pathogenesis of the dilated ascending aorta in this patient and the
      indication for ascending aorta replacement in such cases.

PMID- 21881336
TI  - Acute occlusion of the abdominal aorta with concomitant internal iliac artery
      occlusion.
AB  - Acute aortic occlusion is a rare but catastrophic pathology with high mortality
      even after revascularization. We describe four patients who underwent
      thrombectomy or bypass surgery for acute aortic occlusion with concomitant
      internal iliac artery occlusion. Two patients (82- and 75-year-old men), who had
      insufficient reperfusion of bilateral internal iliac arteries after treatment
      (thrombectomy alone and axillobifemoral bypass, respectively), died on
      postoperative day three of uncontrollable hyperkalemia and multiple organ
      failure, respectively (mortality: 50%). The third patient (74-year-old man), in
      whom the left internal iliac artery was reperfused after an axillobifemoral
      bypass, underwent right lower limb amputation but survived. The fourth patient
      (63-year-old man) with sufficient internal iliac artery reperfusion bilaterally
      after aortobifemoral and right internal iliac artery reconstruction, had an
      uneventful postoperative course. Elevated creatine phosphokinase and
      myoglobinuria levels were observed in all four patients but were notably higher
      in the two patients with no reperfusion in either of the internal iliac arteries.
      Our results suggest that reperfusion of one or more internal iliac arteries may
      be a crucial factor in reducing mortality in revascularization treatment of acute
      aortic occlusion with concomitant internal iliac artery occlusion.

PMID- 21881337
TI  - A successful surgical case of an 80-year-old patient with type A acute aortic
      dissection complicated by preoperative multiple organ failure.
AB  - An 80-year-old woman was hospitalized in a state of shock accompanied by blood
      acidosis due to type A acute aortic dissection complicated by respiratory, liver,
      and kidney failure. A warning was given to her family that lack of intervention
      may possibly lead to an early death, and permission for the intervention was
      obtained. After undergoing a "less invasive quick replacement (LIQR)," a newly
      modified procedure that we had developed, the patient improved gradually, went
      home without any complications, and continues to be well. Emergency surgery for
      octogenarians remains controversial, particularly for patients with a
      preoperative, compassionate indication. Here, we report a survival case for an
      emergency operation using LIQR to treat an octogenarian diagnosed with type A
      acute aortic dissection complicated by multiple organs failure.

PMID- 21881338
TI  - Extremely localized aortic dissection and intussusception of the intimal flap
      into the left ventricle.
AB  - Stanford type A aortic dissection frequently deforms the aortic root and causes
      aortic regurgitation (AR). On the rare occasion, massive AR can occur due to
      circumferential intimal disruption and prolapse of the cylinder-shaped intimal
      flap into the left ventricle. Because of the critical, general, and hemodynamic
      state of such patients, surgery for this condition carries a high risk. A 62-year
      old woman suffered acute chest pain and fell into cardiogenic shock. Computed
      tomography and transthoracic echocardiography failed to identify the etiology of
      this rapid hemodynamic collapse. Transesophageal echocardiography (TEE)
      demonstrated circumferential intimal disruption, 3 centimeters above the aortic
      valve annulus; a very localized aortic dissection in the proximal ascending
      aorta; and a to-and-fro motion of cylinder-shaped intima causing severe AR. The
      dissection did not affect the aorta beyond the intimal tear, and TEE was the only
      useful modality for the diagnosis. Emergency replacement of the ascending aorta
      and resuspension of the aortic valve was successfully performed. Residual AR was
      absent, and the postoperative course was uneventful.

PMID- 21881339
TI  - Unification of T2a and T2b tumors to T2 tumors in non-small cell lung cancer
      staging.
AB  - INTRODUCTION: We investigated the validation of the seventh edition of the TNM
      staging (2009) system for lung cancer, retrospectively. METHODS: From January
      1990 to March 2004, 1629 patients who underwent lung resection with systemic
      lymph node dissection for non-small cell lung cancer at Nippon Medical School and
      Saitama Cancer Center were included. The overall survivals after surgery by each
      pathological stage according to the 1997 and 2009 systems were statistically
      analyzed using Kaplan-Meier estimated survival curves, and the significance of
      the difference was analyzed by the log-rank test. RESULTS: The 2009 system had
      significant prognostic distinction between each T descriptor except for T2a and
      T2b, and between each M descriptor. The 2009 system had better prognostic
      distinction between each pathological stage except for stages IB and IIA, and
      stages IIIB and IV. In the simulation, we unified T2a and T2b tumors into T2
      tumors, and T2bN0M0 and T2bN1M0 were moved to stages IB and IIA, respectively.
      This proposed system had significant prognostic distinction between the proposed
      IB, IIA, and IIB stages. CONCLUSIONS: The 2009 system provides better patient
      selection for surgery and prognostic distinction between each stage except for
      stages IB and IIA, and stages IIIB and IV, compared with the 1997 system.
      Unification of T2a and T2b tumors to T2 tumors can improve prognostic distinction
      between stages IB and IIA.

PMID- 21881340
TI  - Non-invasive evaluation of internal thoracic artery anastomosed to the left
      anterior descending artery with 320-detector row computed tomography and
      adenosine thallium-201 myocardial perfusion scintigraphy.
AB  - PURPOSE: We evaluated the relationship between internal thoracic artery (ITA)
      stenosis anastomosed to the left anterior descending artery (LAD) and the degree
      of LAD stenosis using 320-detector row computed tomography (320-ADCT) and
      adenosine thallium-201 myocardial perfusion scintigraphy (Tl-201-MPS). METHODS:
      We included 101 patients who underwent coronary artery bypass grafting (CABG)
      using ITA grafts; 320-ADCT and adenosine Tl-201-MPS were performed 2-3 months
      after CABG. Clinical parameters, degree of LAD stenosis, and regional myocardial
      ischemia of the LAD territory were compared between patients without ITA stenosis
      (Group A) and with ITA stenosis (Group B). RESULTS: Thirty patients (30%) had
      <=75% LAD stenosis, and 9 patients (30%) showed significant ITA stenosis.
      Regional ischemia was noted in 23 patients (23%). There were no differences in
      clinical parameters between the 2 groups. Twenty-two patients (24%) in Group A
      and 8 patients (89%) in Group B had <=75% LAD stenosis (P <0.002). No Group B
      patients had regional myocardial ischemia of the LAD territory. CONCLUSION: We
      concluded that <=75% LAD stenosis significantly influences ITA stenosis, without
      associated regional myocardial ischemia of the LAD territory. Non-invasive 320
      ADCT and adenosine Tl-201-MPS for ITA evaluation may be useful for long-term
      follow-up of patients after CABG.

PMID- 21881341
TI  - A case of Mullerian cyst arising in posterior mediastinum.
AB  - A mediastinal Mullerian cyst was initially reported as a new category of
      congenital cyst by Hattori, et al. in 2005. We treated a 53-year-old female
      referred to us with a posterior mediastinal tumor found at the Th5 prevertebral
      level by chest-computed tomography during a medical check-up. She had a history
      of mediastinal teratoma, which was removed at the age of 35. Chest magnetic
      resonance imaging revealed homogenous, high-intensity signals in T2-weighted
      images. The lesion was resected using a thoracoscopic procedure, and histologic
      and immunohistochemical staining revealed a ciliated cyst of Mullerian origin.
      The newly established mediastinal Mullerian cyst should be included in the
      differential diagnosis of posterior mediastinal cysts.

PMID- 21881342
TI  - The cervical anterior approach for the resection of superior posterior neurogenic
      tumor: a case report.
AB  - Many approaches for resection of the superior mediastinal tumors have been
      reported. We introduce an approach, which we call the cervical anterior approach.
      This approach is only cervical and does not require a sternotomy. Merits of this
      approach include the ability to remove the tumor without opening the mediastinal
      or parietal pleura, as well as obviating draining the thoracic cavity. The tumor
      is also directly visible, and the surgeon can avoid injury to the great vessels.
      This approach is recommended when the tumor is located superior to the third
      thoracic vertebra level, when it borders the great vessels, and when it does not
      border the trunk of the brachial plexus or nerve root. This approach is easy and
      safe for surgical procedures.

PMID- 21881343
TI  - Successful resection of mediastinal seminoma evaluated the response to induction
      chemotherapy with fluorodeoxyglucose-positron emission tomography.
AB  - Mediastinal seminoma is a rare malignant tumor, and the current strategy for
      primary mediastinal seminomas is making a prompt diagnosis and achieving an
      appropriate chemotherapy. However, consensus regarding the optimal post
      chemotherapy management has not been reached. We experienced a case of 26-year
      old man who was diagnosed mediastinal seminoma and evaluated the response to
      induction chemotherapy with fluorodeoxyglucose-positron emission
      tomography/computed tomography (FDG-PET/CT). Complete surgical excision of the
      tumor was performed. Pathologic findings of the surgical specimen showed no
      viable cells in the tumor.

PMID- 21881344
TI  - Coronary artery and mitral valve surgery in Takayasu's arteritis: a case report.
AB  - Concomitant coronary artery disease and mitral valve disease are rare in
      Takayasu's Arteritis. Our patient had Takayasu's Arteritis diagnosed 9 years ago.
      She had an inferior myocardial infarction and double stent implantation 8 months
      ago. She was admitted to the hospital for chest pain, and 3 vessel diseases were
      diagnosed with significant mitral regurgitation due to anterior leaflet prolapse.
      In this report, we present perioperative management of our patient who underwent
      coronary artery bypass grafting and mitral valve replacement.

PMID- 21881345
TI  - Deformities of pulmonary and aortic annulus 42 years after repair of tetralogy of
      Fallot.
AB  - We report an extremely rare case of deformity of the pulmonary sinus of Valsalva
      with pulmonary valvular stenosis 42 years after a pulmonary annular-sparing
      operation for tetralogy of Fallot. Aortic regurgitation with deformity of the
      sinus is also noted. At the previous operation, the right ventricular outflow
      tract was augmented by a prosthetic subvalvular patch. Through the years, the
      pulmonary valve and sinus were distorted because the patch was pulled over toward
      the right ventricle.

PMID- 21881346
TI  - Surgical ventricular restoration improves the left ventricle basal wall function
      using quantitative gated SPECT.
AB  - OBJECTIVE: It is not clear whether surgical ventricular restoration (SVR) or
      procedures approaching mitral complex for controlling functional mitral
      regurgitation (MR) affect the regional left ventricular wall function. The
      purpose of the present study was to evaluate the regional LV function after SVR
      using overlapping left ventriculoplasty (OLVP) using quantitative gated
      myocardial perfusion SPECT (QGS). PATIENTS AND METHOD: Forty-one heart failure
      patients, including those with ischemic cardiomyopathy (ICM) (n = 25) and non-ICM
      (NICM) (n = 16), underwent SVR and/or papillary muscle approximation (PMA). The
      rest myocardial perfusion SPECT were performed before and early after operation
      (mean 25.8 +/- 10.6 days). These patients were divided into 4 groups based on the
      surgical procedures (SVR and/or PMA) and etiology of patients (ICM or NICM) as
      follows: SVR (with or without PMA) of ICM, SVR of NICM, PMA of ICM and PMA of
      NICM groups. The regional wall thickening was compared before and after the
      operation between the four groups. RESULTS: NYHA functional classes were improved
      after the operation in all four groups. MR grade was also improved in three
      groups other than SVR of the ICM group. The left ventricular basal wall
      thickening was improved postoperatively in following three groups (SVR of ICM:
      12.7 +/- 3.8% to 16.5 +/- 4.6% p <0.05, PMA of ICM: 11.1 +/- 4.3% to 14.9 +/-
      4.8% p <0.05, SVR of NICM: 5.8 +/- 6.6% to 12.3 +/- 6.4% p <0.05), whereas PMA of
      the NICM group did not show an improvement. Wall thickening in the middle and
      distal levels was not improved in all groups. CONCLUSION: OLVP improved NYHA
      functional classes, and also improved the regional wall function at the basal
      level of the left ventricle. In contrast, lone PMA did not improve or impair the
      regional wall function at any of the levels.

PMID- 21881348
TI  - Intrapericardial diaphragmatic hernia after coronary artery bypass grafting using
      the right gastroepiploic artery graft: report of a case.
AB  - Surgeons should be aware of diaphragmatic hernia in obese patients who have
      undergone coronary artery bypass grafting (CABG) using a gastroepiploic artery
      graft (GEA), even if the antegastric route is utilized.We report a case of
      diaphragmatic hernia, which occurred 88 months after initial CABG. A 64-year-old
      obese man underwent surgical repair of a diaphragmatic hernia. At initial
      surgery, the diaphragm was incised vertically and re-sutured, leaving a route for
      GEA graft. Both the stomach and the lateral segment of the liver were dislocated
      in the pericardial space. The diaphragmatic defect was closed with a
      polytetrafluoroethylene patch.

PMID- 21881347
TI  - Major airways trauma, management and long term results.
AB  - PURPOSE: The number of patients with traumatic and iatrogenic tracheobronchial
      injuries is increasing. Early diagnosis, prompt establishment of a secure airway,
      and appropriate management could prevent sequelae and lead to a good outcome.
      METHODS: Between "1994-2007", 35 patients with major airways trauma were managed.
      This descriptive and retrospective study evaluates clinical findings, diagnostic
      approaches, initial managements, definitive surgical or nonsurgical treatments
      and follow-up results. SPSS was used for descriptive outcomes. RESULTS: There
      were 27 males (77%) and 8 females, with a mean age of 28.2. There were 16 blunt,
      11 penetrating and 8 iatrogenic traumas, at the level of the larynx in 1, larynx
      and hypopharynx in 3, laryngotracheal in 12, tracheal in 13, tracheobronchial in
      1, and main bronchi in 5 patients. Fourteen patients (40%) were initially
      managed, and 21 patients were referred to us after their initial managements at
      outside hospitals. There were 7 complications (20%); one resulted in mortality
      (2.9%). The overall final results were good in 57.1%, acceptable in 31.4% and
      poor in 5.7% of patients, (mean follow-up time, 58.2 months). The respiratory
      status and the phonation looked better in the initially managed than the delayed
      managed group. CONCLUSION: We recommend that, patients only become respiratory
      stable with minimum intervention and then be referred to centers with sufficient
      experience in airway surgery.

PMID- 21881349
TI  - A surgical case of prosthetic valve endocarditis with a difficult diagnosis.
AB  - Early diagnosis and treatment of prosthetic valve endocarditis (PVE) is important
      because it has a high mortality rate. We report a case of PVE which was difficult
      to diagnose. A 36-year-old man, who had undergone an aortic valve replacement
      (AVR) 7 years prior, was hospitalized with a high fever of unknown origin. We
      could not detect a stuck valve, vegetations or abscesses using echocardiography,
      and the peak aortic transvalvular pressure gradient had increased to 81 mmHg. We
      suspected PVE and initiated intravenous antibiotic therapy immediately. On day 5,
      echocardiography demonstrated an abnormal shadow directly under the prosthesis,
      and we definitively diagnosed PVE and performed an operation. Intraoperatively,
      the prosthesis was not vegetative, but the left ventricular outflow tract was
      filled with vegetation that was nearly obstructing it. After dissecting the
      infectious focus, we performed a re-AVR. Postoperative echocardiography showed
      that the peak left ventricular aortic pressure gradient decreased to 30 mmHg.
      Obstructive vegetation is difficult to diagnose by preoperative echocardiography.

PMID- 21881350
TI  - Successful closure of a patent ductus arteriosus using an aortic stent graft.
AB  - Closure of patent ductus arteriosus (PDA) in the elderly is a high-risk procedure
      due to the fragility of the aorta and aneurysmal changes in the ductus. Stent
      grafting has emerged as a method for treating aortic disease. We describe a case
      in which this endovascular technique was successfully performed for closure of a
      PDA with aneurismal change in a high-risk patient. This approach may comprise the
      armamentarium for treating this pathology in adults.

PMID- 21881351
TI  - A case of diffuse large B-cell lymphoma of the lung demonstrating diffuse ground
      glass shadows.
AB  - We report a case of 77-year-old woman suffering from breathlessness on exertion
      and dry cough. Chest computed tomography (CT) showed diffuse ground-glass
      shadows. A video-assisted thoracoscopic lung biopsy resulted in the diagnosis of
      diffuse large B-cell lymphoma (DLBCL). Gene rearrangement analysis using
      polymerase chain reaction (PCR) technique was performed on the cells in
      bronchoalveolar lavage (BAL) fluid, and showed the clonality of the
      immunoglobulin heavy chain (IgH) gene, supporting the diagnosis. DLBCL should be
      considered in the differential diagnosis of diffuse ground-glass shadows in the
      chest CT, and gene rearrangement analysis may have an impact on the diagnosis of
      pulmonary DLBCL.

PMID- 21881352
TI  - Acute aortic dissection with intestinal ischemia: what to do first.
AB  - PURPOSE: In the case of an acute aortic dissection, a surgical aortic procedure
      is usually the priority in order to restore the perfusion of vital organs.
      Afterwards, associated ischemic abdominal visceral lesions can be resected. For
      particular patients, it could be highly beneficial to perform the abdominal
      surgery before surgically addressing the aorta. The aim of this paper is to
      contribute to the therapeutic choice in cases of acute aortic dissection with
      acute abdomen. CASE REPORT: The case is reported of a 38-year-old patient,
      affected by an acute aortic dissection (Stanford type A) and
      peritonitis.Suspecting the necessity for a complex combined surgical procedure,
      the patient underwent emergency diagnostic laparoscopy, which showed an
      infarctual necrosis of the distal ileum and right colon. Therefore, he
      immediately underwent a wide right hemicolectomy. Afterwards, an ascending aortic
      substitution was performed.The patient was discharged on the 15th post-operative
      day, and he is doing well, 1 year and 3 months after the operation. CONCLUSION:
      In the case of an acute aortic dissection with acute abdomen, emergency
      laparoscopy is a precious surgical technique to identify criteria that can lead
      to therapeutic decisions, including timing.

PMID- 21881353
TI  - Effects of olmesartan on the renin-angiotensin-aldosterone system for patients
      with essential hypertension after cardiac surgery--investigation using a
      candesartan change-over study.
AB  - BACKGROUND: Various angiotensin II receptor blockers are widely used for the
      treatment of hypertension in recent years. The results of large-scale clinical
      studies have shown that they have various efficacies: not only hypotensive
      effects but also organ protective effects. In this study, the effects of a change
      over from candesartan to olmesartan on renin-angiotensin-aldsterone system,
      cardiomegaly and peripheral circulation were studied. METHODS: Participants
      enrolled in this trial were outpatients with essential hypertension after cardiac
      surgery who had received candesartan for more than one year. Fifty-six patients
      switched from candesartan to olmesartan. The primary endpoints were 1) renin
      activity, angiotensin II, aldosterone, and 2) left ventricular mass index (LVMI).
      RESULTS: It was clear that angiotensin II and aldosterone are decreased by the
      potent hypotensive effects of olmesartan in a change-over from candesartan to
      olmesartan. Since LVMI and BNP were decreased, inhibitory effects on myocardial
      hypertrophy were also confirmed. CONCLUSION: In the present study, left
      ventricular hypertrophy and on arterial compliance were inhibited by a decrease
      in angiotensin II and aldosterone due to the change-over to olmesartan. In the
      future, protective effects on organs will be clarified by long-term observations.

PMID- 21881355
TI  - Emergency coronary artery bypass grafting for left main shock syndrome.
AB  - OBJECTIVE: Acute myocardial infarction (AMI) complicated by cardiogenic shock and
      left main coronary artery disease (left main shock syndrome) shows high
      morbidity, and whether early coronary artery bypass grafting (CABG) improves the
      clinical outcome remains unclear. METHODS: Six consecutive patients (mean age,
      61.6 years) with MI complicated by left main shock syndrome underwent emergency
      CABG. Patients were divided into 2 groups according to the time from MI to
      reperfusion; within 8 hours in 3 patients and beyond 8 hours in the remaining.
      Average postoperative peak creatinine kinase (CK) and creatinine kinasemyosin
      band (CK-MB) levels were recorded, and the ejection fraction (EF) was measured
      with ultrasound cardiography. RESULTS: Significant differences in postoperative
      EF and CPK-MB were observed between the 2 groups. The 30-day survival rate was
      100%. Five patients left the hospital alive, while 1 died on postoperative day
      78. CONCLUSIONS: AMI complicated by cardiogenic shock and left main coronary
      artery disease can be effectively treated with emergency CABG, with acceptable
      mortality and morbidity. Emergency CABG for MIs within 8 hours can improve
      survival in patients with left main shock syndrome.

PMID- 21881354
TI  - A clinical study of the prognostic factors for postoperative early recurrence in
      patients who underwent complete resection for pulmonary adenocarcinoma.
AB  - PURPOSE: The 2-[F-18]-Fluoro-2-deoxy-D-glucose (FDG) uptake in positron emission
      tomography (PET) and serum neutrophil/lymphocyte ratio (NLR) are recently
      noteworthy prognostic factors. We studied the prognostic factor to predict early
      recurrence after curative resection for pulmonary adenocarcinoma including FDG
      uptake and NLR. METHODS: We performed a retrospective review of 23 patients who
      underwent a complete resection for pulmonary adenocarcinoma. The patients were
      divided into 2 groups: 19 patients in the disease-free group, and 4 patients in
      the recurrent group. Clinical and pathological factors concerning the recurrence
      within 1 year of surgery were analyzed between two groups. RESULTS: No
      significant differences between the recurrent group and disease-free group was
      seen in age, gender, CEA, NLR, CRP, pathological stage, pleural invasion,
      pathological grading, Ki-67 expression, venous invasion and lymphatic invasion.
      The SUVmax was significantly elevated in the recurrent group (12.5 +/- 2.01 vs.
      5.70 +/- 3.97, p = 0.0094). Tumor size was significantly larger in the recurrent
      group (5.58 +/- 0.71 vs. 3.62 +/- 1.33 cm, p = 0.0058). The first, recurrent
      sites in 4 patients were brain, in 3 patients; and lung, in 1 patient.
      CONCLUSION: Both tumor size and SUVmax are possible predictors of early
      recurrence after curative resection in patients with pulmonary adenocarcinoma.
      Although it is impossible to determine the SUVmax as an independent prognostic
      factor, the SUVmax may be one of the predictors of early hematogenous recurrence
      in surgically treated pulmonary adenocarcinoma.

PMID- 21881357
TI  - Teratoma with naturally occurring malignant transformation in a child.
AB  - We present a 12-year-old girl with a teratoma with malignant transformation (TMT)
      of the mediastinum. Computed tomography showed a cystic mass (5.0 cm * 4.0 cm)
      with a thick solid portion, in the anterior mediastinum. Six months later, the
      solid portion of the mass had enlarged, and surgical resection was performed. The
      resected tumor was 7.0 * 5.0 * 4.0 cm in size. The cystic portion was a mature
      teratoma, and the solid portion predominantly comprised a viable embryonal
      rhabdomyosarcoma. There were no immature teratomatous elements or other germ-cell
      components. The histopathologic diagnosis was a mature teratoma with embryonal
      rhabdomyosarcoma, a so-called TMT. The tumor recurred, despite adjuvant
      chemotherapy. The patient died of progressive disease 16 months postoperatively.
      To the best of our knowledge, no naturally occurring TMT of the mediastinum has
      previously been reported in a child. Surgical resection at an early stage is
      necessary.

PMID- 21881356
TI  - Female gender is an independent prognostic factor in non-small-cell lung cancer:
      a meta-analysis.
AB  - PURPOSE: It is not clear whether women with non-small-cell lung cancer (NSCLC)
      live significantly longer than men. Thus, we conducted a meta-analysis of
      published studies to quantitatively compare NSCLC survival data between genders.
      MATERIALS AND METHODS: A MEDLINE Web search for computer-archived bibliographic
      data regarding overall survival differences between genders was performed.
      DerSimonian-Laird random effects analysis was used to estimate the pooled hazard
      ratio (HR). RESULTS: We selected 39 articles as appropriate data sources,
      involving 86 800 patients including 32 701 women and 54 099 men. Combined HRs for
      women vs. men in studies using univariate and multivariate analyses respectively
      were 0.79 (p <0.0001) and 0.78 (p <0.0001). Pooled HRs for 3 study subgroups
      having (1) fewer than 30% stage I cases, (2) fewer than 50% adenocarcinoma cases,
      and (3) statistical adjustment for smoking status all indicated the survival
      advantage of women. CONCLUSION: This meta-analysis of published data concerning
      NSCLC patients indicated significantly better survival for women.

PMID- 21881358
TI  - Two lung adenocarcinomas in the same lobe: multiple primaries or intrapulmonary
      metastasis?
AB  - Abnormal nodules were found in the left lung of a 52-year-old woman in segments 6
      and 10 on a chest CT. These nodules showed no changes for 18 months, and we
      discontinued follow-up. Almost 5 years later, an abnormal shadow was found in her
      left lower lung field on a medical check-up chest X-ray. Chest CT revealed that
      the left segments 6 and 10 nodules had grown. We diagnosed these lesions as
      synchronous double primary lung cancers in the same lobe based on the disease
      history and performed a left lower lobectomy and lymph node dissection.
      Pathological examination of both tumors revealed adenocarcinoma of a mixed
      subtype with papillary and bronchioloalveolar carcinoma. Epidermal growth factor
      receptor gene mutations were examined, and the 2 lesions shared an L858R
      mutation. Although we expected EGFR gene mutation analysis would help us
      distinguish the 2 lesions from each other, it was of little help. Disease history
      can be more important in evaluating multiple pulmonary cancers.

PMID- 21881359
TI  - A surgical case of mitral regurgitation due to active infective endocarditis with
      idiopathic thrombocytopenic purpura.
AB  - A 71-year-old woman with idiopathic thrombocytopenic purpura (ITP), who had been
      treated with steroid and cyclosporine, was admitted in an emergency with fever
      and dyspnea. The diagnosis was mitral regurgitation due ton infective
      endocarditis. Although she received treatments for infection and cardiac failure,
      the cardiac failure could not be controlled. After high-dose gamma-globulin
      therapy, an emergency operation was performed during the active phase of
      infective endocarditis. Rapid platelet transfusion was administered after weaning
      from extracorporeal circulation. She recovered and was discharged without
      postoperative bleeding and re-infection.The treatment course of elective cardiac
      surgery complicated with ITP has been established, but the course of emergency
      surgery has not been established because of the small number of cases reported.
      Since few patients have undergone emergency surgery for active infective
      endocarditis, we had difficulty in deciding the time of surgery and treatment for
      increasing the number of platelets before surgery, it was considered that the
      case provided us with useful suggestion for the future treatment for urgent
      surgery complicated with ITP.

PMID- 21881360
TI  - Intrapulmonary-located Castleman's disease, which was surgically resected without
      pulmonary resection.
AB  - Castleman's disease (CD) is a rare disease with unknown aetiology. It is
      characterised by benign lymph node hyperplasia that may involve all lymph nodes.
      The most common locations are the mediastinum and abdomen. CD arising from
      intrapulmonary lymph nodes has been reported in five cases, in the English
      language literature to date. Tumours in these patients are usually resected
      during lung surgery. An asymptomatic 29-year-old male patient was evaluated due
      to a mass lesion with a diameter of 55 mm located in the infrahilar region of the
      right lung with a high degree of contrast enhancement on thoracic computed
      tomography (CT). Vascularity of this central lesion was excluded by pulmonary
      angiography. Thoracotomy was performed due to the inability to obtain a diagnosis
      with percutaneous fine needle aspiration biopsies. A frozen section examination
      of the mass revealed a benign lesion, arising from the intrapulmonary lymph nodes
      and protruding to the lower-lobe parenchyma. The mass was then extracted from the
      parenchyma. After histopathological evaluation of the mass, CD involving the
      lymph nodes was diagnosed. CD rarely involves the intrapulmonary lymph nodes.
      Diagnosis is difficult in these patients, and thoracotomy may be required. After
      obtaining benign results by mass sampling, limited resection of these masses,
      while sparing the lung parenchyma, may be possible.

PMID- 21881362
TI  - Spontaneous regression of primary lung cancer arising from an emphysematous
      bulla.
AB  - Bullous emphysema is an important risk factor for lung cancer. Here, we report
      the case of a 56-year-old man who underwent surgical treatment for primary lung
      cancer arising from the wall of a bulla. Chest computed tomography (CT) had
      revealed a nodule arising from the bulla wall. This nodule showed positive uptake
      of (18)fluorodeoxyglucose (FDG) during positron emission tomography (PET)-CT.
      However, repeat CT performed after 2 months showed a spontaneous decrease in the
      tumor size. Exploratory resection revealed non-small cell lung cancer, which was
      confirmed by the findings of intraoperative frozen-section analysis; therefore,
      right upper lobectomy and mediastinal lymph node dissection were performed. The
      postoperative, pathological diagnosis was squamous cell carcinoma arising from
      the wall of a bulla. From this case, we infer that lung cancer arising from the
      wall of a bulla may spontaneously regress, and FDG/PET is a useful tool to
      diagnose lung tumor in patients with pulmonary bullous disease.

PMID- 21881363
TI  - Long-term extracorporeal membrane oxygenator support in resuscitation for
      intractable hibernating myocardium after coronary artery bypass grafting.
AB  - We report our experience of long-term extracorporeal membrane oxygenator (ECMO)
      support to resuscitate a 62-year-old man who had critical three-vessel disease of
      coronary artery complicating intractable hibernating myocardium (HM) and sudden
      cardiogenic shock. Intra-aortic balloon pump and ECMO were deployed to restore
      the circulatory support while emergent revascularization surgery was
      performed.The patient was weaned from ECMO successfully after 15 days of support
      and discharged with recovered left ventricular function. ECMO is effective in
      resuscitation of patients with cardiogenic shock and HM. To our knowledge the
      present case necessitated the longest term of ECMO support to get rid of HM.

PMID- 21881361
TI  - Mitral valve repair in a patient with myelodysplastic syndrome.
AB  - Open heart operations for patients with myelodysplastic syndrome (MDS) are
      associated with infective and bleeding complications. We report a 67-year-old
      woman with rheumatic, severe mitral regurgitation and mitral stenosis associated
      with MDS who underwent a mitral valve (MV) repair. Commissurotomy was performed
      in the anterior commissure. Autologous pericardial patch treated with
      glutaraldehyde solution was prepared. The anterior leaflet was completely
      detached from the posterior to the anterior commissure. The anterior leaflet was
      augmented by autologous pericardial patch treated with glutaraldehyde solution
      and three pairs of artificial chordae were implanted. Postoperative
      transesophageal echocardiography showed an increase in the MV orifice and less
      than trivial mitral regurgitation. Two years after the operation, the patient has
      normal sinus rhythm with no deterioration of the MV lesion by transthoracic
      echocardiography. Although the feasibility of MV repair is low in patients with
      restrictive pathology due to rheumatic disease, MV repair may be preferred in
      patients with MDS.

PMID- 21881364
TI  - Off-pump coronary artery bypass grafting as re-do surgery in two cases in which
      the right gastroepiploic artery was grafted to the right coronary artery.
AB  - Transdiaphragmatic off-pump coronary artery bypass grafting (OPCAB) to the right
      coronary artery, is an effective way to reduce the risks of second bypass surgery
      as well as the risk of graft injury after coronary artery bypass grafting (CABG).
      We report two cases of successful OPCAB as re-do surgery in which the right
      gastroepiploic artery (RGEA) was grafted to the right coronary artery. The first
      case was a 58-year-old woman, who underwent CABG 10 years ago. OPCAB (RGEA to
      right coronary artery) was performed since myocardial perfusion scintigraphy
      revealed ischemia in the inferior wall. The second case was a 67-year-old man who
      had hypertension, hyperlipidemia, peripheral arterial disease, and was undergoing
      dialysis (for 6 years). Six years previously, he developed a mycotic aneurysm of
      the right coronary artery and underwent open-heart surgery. He often had episodes
      of angina at night or during dialysis, and then developed congestive heart
      failure and was hospitalized. Since ischemia was considered to be in the inferior
      wall, the RGEA was grafted to the right coronary artery.

PMID- 21881365
TI  - Acute exacerbation of idiopathic pulmonary fibrosis of microscopic usual
      interstitial pneumonia pattern after lung cancer surgery.
AB  - A 78-year-old man underwent right lower lobectomy for lung cancer.
      Histopathological examination led to the diagnosis of adenosquamous cell
      carcinoma. The background lung adjacent to the pleura showed idiopathic pulmonary
      fibrosis of microscopic usual interstitial pneumonia pattern, although
      preoperative computed tomography showed no apparent findings of interstitial
      pneumonia. The patient showed an acute exacerbation of idiopathic pulmonary
      fibrosis on the third postoperative day. We herein report a case of acute
      exacerbation of idiopathic pulmonary fibrosis of microscopic usual interstitial
      pneumonia pattern after lung cancer surgery.

PMID- 21881366
TI  - Aortic valve replacement combined with the endoventricular patch technique for
      aortic valve stenosis complicated by ischemic heart disease.
AB  - The indication for aortic valve replacement (AVR) combined left ventricular (LV)
      plasty in the patient with aortic valve stenosis (AS) complicated by ischemic
      heart disease is controversial. We describe a case of AS with ischemic heart
      disease of a patient who underwent a successful surgical treatment, AVR combined
      with the endoventricular patch technique. The patient was an 82-year-old woman
      who suffered from heart failure, New York Heart Association (NYHA) class III. The
      heart failure derived from AS and ischemic heart disease with severely
      compromised LV function. She underwent AVR combined with the endoventricular
      patch technique and the postoperative course was uneventful. She has been well
      with NYHA class I for about 5 years after the operation without heart failure.

PMID- 21881368
TI  - A case of atherosclerotic aneurysm of the right subclavian artery with the right
      axillary arterial stenosis and enlargement of the ascending aorta.
AB  - A 54-year-old man presented with neck pain and hoarseness. Angiography showed a
      rare right subclavian artery aneurysm, enlargement of the ascending aortic
      aneurysm, and axillary artery stenosis. These aneurysms would normally be treated
      with end-to-end anastomosis, but due to the complexity of the lesion in this
      case, we performed more extensive surgery. This consisted of successful
      reconstruction of the subclavian artery and replacement of the ascending aorta
      and aortic arch.

PMID- 21881367
TI  - Thoracic endovascular aortic repair and off-pump coronary artery bypass grafting
      after renal transplantation: a case report.
AB  - Twelve years after receiving a renal transplant, a 50-year-old woman developed
      asthmatic symptoms. Chest CT revealed a descending thoracic aortic aneurysm. She
      had undergone percutaneous coronary intervention to treat the left anterior
      descending artery 10 years earlier. Coronary artery angiography revealed
      restenosis of the left anterior descending artery (99%, #6 in-stent). Because
      cardiopulmonary bypass may cause problems for transplanted kidney, we performed
      off-pump coronary artery bypass grafting (left internal thoracic artery to left
      anterior descending artery) and thoracic endovascular graft placement to treat
      the aortic aneurysm. Considering that the artery of the transplanted kidney was
      attached to the right iliac artery, and then the left common femoral artery was
      selected as the access root for GORE TAG((r)) endografts (34 * 200 and 34 * 150
      mm) (stentgrafts were deployed for the descending aortic artery). Postoperative
      angiography showed a patent bypass graft. Postoperative CT confirmed the absence
      of endoleaks. The postoperative course was uneventful, and she was discharged
      without complications. Ischemic heart disease and descending thoracic aortic
      aneurysm in recipients of kidney transplants can be treated using off-pump
      coronary bypass grafting and thoracic endovascular graft placement. The
      transplanted kidney was protected without using cardiopulmonary bypass (CPB).

PMID- 21881369
TI  - Successful excision of an isolated mediastinal cystic lymphangioma with bilateral
      thoracoscopic surgery.
AB  - Lymphangioma is a well-known benign tumor and its cystic abnormalities of the
      lymph vessels are predominantly congenital. Cystic lymphangioma usually occurs in
      the neck, axillary region, and rarely in the mediastinum, which frequently occurs
      in children and young adults. A 20-year-old woman had symptoms of palpitation,
      cough, and dyspnea during the recent 1 month. Both chest comuted tomography and
      magnetic resonance imaging of the chest revealed a well-defined, 13 * 10-cm
      cystic lesion in the anterior mediastinum. The patient underwent bilateral video
      assisted thoracoscopic excision of the cyst and lymphangioma was confirmed based
      on histopathologic examination. Here, we report a rare case of isolated
      mediastinal cystic lymphangioma that was successfully excised using a minimally
      invasive technique.

PMID- 21881370
TI  - Thoracoscopic lobectomy for treating cancer in a patient with an unusual vein
      anomaly.
AB  - Various anatomical variants in pulmonary veins can have a serious effect on
      patients undergoing lung surgery. We present a case of a patient with an unusual
      pulmonary vein variation. Preoperative review of the patient's three-dimensional
      64-row multidetector computed tomography imaging allowed us precise simulation
      and good orientation of the patient's vascular variant anatomy during surgery.
      Upper lobectomy through thoracoscopic approach was performed successfully in the
      case where the middle lobe vein might have been divided without preoperative
      anatomical evaluation by 3D CT images.

PMID- 21881371
TI  - The effects of preoperative short-term intense physical therapy in lung cancer
      patients: a randomized controlled trial.
AB  - BACKGROUND: We planned to investigate the effect of preoperative short period
      intensive physical therapy on lung functions, gas-exchange, and capacity of
      diffusion, and ventilation-perfusion distribution of patients with non-small cell
      lung cancer. METHODS: Sixty patients with lung cancer, who were deemed operable,
      were randomly allocated into two groups. Intensive physical therapy was performed
      in patients in the study group before operation. Both groups received routine
      physical therapy after operation. RESULTS: There was no difference in pulmonary
      function tests between the two groups. Intensive physical therapy statistically
      significantly increased peripheral blood oxygen saturation. At least one
      complication was noted in 5 patients (16.7%) in the control group, and 2 (6.7%),
      in the study group. However, there was no statistically significant difference (p
      = 0,4). The hospital stay has been found to be statistically significantly
      shortened by intensive physical therapy (p <0.001). Ventilation-perfusion
      distribution was found to be significantly effected by intensive physical
      therapy. The change was prominent in the the contralateral lung (p <0.001).
      CONCLUSIONS: Intensive physical therapy appeared to increase oxygen saturation,
      reduce hospital stay, and change the ventilation/perfusion distribution. It had a
      significant, positive effect on the exercise capacity of patients.

PMID- 21881372
TI  - Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension
      : a systematic review.
AB  - PURPOSE: Pulmonary thromboendarterectomy (PTE) is a treatment option for patients
      with chronic thromboembolic pulmonary hypertension (CTEPH). The present
      systematic review was performed to assess the safety and efficacy of PTE for
      CTEPH. METHODS: A systematic review was performed, and six electronic databases
      were searched for published studies from January 1999 to February 2010. All
      articles that presented morbidity and mortality data, survival data or
      preoperative and postoperative pulmonary hemodynamic indices were included. The
      primary outcome measures extracted were early morbidity and mortality, pulmonary
      hemodynamic and functional outcome indices prior to and after the operation, and
      survival data. RESULTS: Of the 654 publications retrieved, 19 relevant papers
      (total number of 2729 patients) representing the most recent and complete data
      set from each institute, were included for appraisal and data extraction. No
      randomized controlled trials or matched comparative studies were identified.
      Thirty-day mortality ranged from 1.3% to 24% (median 8%). Residual pulmonary
      hypertension was reported in 11%-35% of patients after PTE. Pulmonary artery
      pressure and pulmonary vascular resistance significantly decreased after PTE in
      all studies. Before PTE, 60%-100% of patients were in NYHA functional class III
      or IV. This percentage decreased to 0%-21% after PTE. Five-year survival ranged
      from 74% to 89%. CONCLUSIONS: The current literature suggests that PTE for
      patients with CTEPH is associated with acceptable perioperative morbidity and
      mortality rates and improved hemodynamic indices and survival when viewed against
      the prognosis associated with historical controls using medical therapy.

PMID- 21881373
TI  - Optimal culture conditions for constructing durable biografts for repairing the
      impaired heart--dynamic cell culture with pre-seeding.
AB  - BACKGROUND: Tissue engineering with cell seeded biodegradable material has
      attracted attention as a novel means of treating the severely impaired heart.
      Here, we consider optimal preparation of a durable biograft using dynamic and
      static cultures. METHODS: Vascular smooth muscle cells (VSMCs) derived from the
      rat aorta were seeded onto biodegradable material P (LA/CL) (poly-L-lactide
      epsilon-caprolactone copolymer) and cultured as follows: a) Static culture (n =
      11), b) dynamic culture (n = 12), c) 0 h pre-seeding (n = 12), d) 24 h pre
      seeding (n = 5) and e) 1 week pre-seeding (n = 12). Dynamic culture: Cells were
      cultured in spinner flasks. Pre-seeding: Static cell seeding and culture before
      dynamic culture. EVALUATION: The conditions of the P (LA/CL) in the five groups
      were evaluated as cell proliferation and by histological studies. RESULTS: VSMCs
      proliferated both in and on the biodegradable materials. The quality of the
      dynamic culture cell with pre-seeding increased. Although the duration of pre
      seeding exerted no significantly different effects, cell attachment and
      proliferation were widely scattered in the 0 h pre-seeding group, whereas cells
      proliferating on the front of the scaffold obstructed proliferation inside the
      biodegradable material in the 1 week pre-seeding group . CONCLUSIONS: Dynamic
      cell culture with 24 h pre-seeding is effective for constructing ideal biografts.

PMID- 21881374
TI  - Does postoperative serum interleukin-6 influence early recurrence after curative
      pulmonary resection of lung cancer?
AB  - PURPOSE: We examined the influence of inflammatory cytokine levels on
      postoperative early recurrence in patients who underwent curative lung cancer
      surgery. METHODS: In 107 patients who underwent curative pulmonary resections for
      non-small cell lung cancer (NSCLC) from November 2007 to June 2008, we measured
      serum interleukin-6 (IL-6) levels preoperatively, and on postoperative day (POD)
      0, 1, and 2. Between July 2009 and August 2009, 1 year after the date of
      enrollment of the last patient, we investigated survival status of each patient
      and identified a group with recurrence. RESULTS: Among 107 patients, 29 patients
      developed recurrence with a mean follow-up of 18.1 months (range 14 to 21). P
      stage was significantly more advanced in the recurrence group than in the non
      recurrence group (p = 0.005). Serum IL-6 levels on POD 1 were significantly
      higher in the recurrence group than in the non-recurrence group (p = 0.007). In
      Cox's proportional hazards regression, P-stage and serum IL-6 levels on POD 1
      were significant independent predicting factors for postoperative early
      recurrence (p = 0.006, p = 0.003). CONCLUSIONS: The higher the serum IL-6 levels
      on POD 1, the higher the risk of early postoperative recurrence, even when
      curative pulmonary resection can be accomplished in lung cancer patients.

PMID- 21881375
TI  - Training in robotic surgery using the da Vinci(r) surgical system for left
      pneumonectomy and lymph node dissection in an animal model.
AB  - OBJECTIVES: In Japan, as of March 2010, only 13 hospitals were using the da
      Vinci(r) system and only for selected cases. Few clinical robotic lung surgery
      has been done in Japan, and there are no standardized training programs, although
      some exist in the U.S. and are under consideration by the Japanese society for
      thoracic surgery. We have used the da Vinci S(r) Surgical System for
      pneumonectomy and lymph node dissection in pigs. We report and review future
      possibilities and problems of robotic surgery, especially concerning education,
      training, safety management and ethical considerations for pneumonectomy and
      lymph node dissection in clinical practice. METHODS: The da Vinci(r) system
      consists of a surgeon's console connected to a patient-side cart, a manipulator
      unit with three instrument arms and a central arm to guide the endoscope. The
      surgeon, sitting at the console, triggers highly sensitive motion sensors that
      transmit the surgeon's movements to the instrument arm. RESULTS: We experienced
      exactly the same sensation as when performing standard open thoracotomy. Visual
      recognition is 3-D, and the high manipulation potential allows free movement of
      the various accessory instruments, exceeding the capacity of a surgeon's hands in
      video-assisted thoracic surgery (VATS) or even standard thoracotomy. CONCLUSIONS:
      Robotic surgery achieves at least the same level of operation technique for
      pneumonectomy and lymph node dissection under standard open thoracotomy, and it
      seemed as safe and easily performed as conventional VATS. The training program
      using pigs was effective and holds promise as a system to train thoracic surgeons
      in robotic lung surgery.

PMID- 21881376
TI  - Hyperparathyroidism due to eutopic PTH secretion from an ectopic intrathymic
      parathyroid cyst.
AB  - Parathyroid cysts rarely cause hyperparathyroidism. In addition, they rarely
      occur in the thymus. We report a 56-year-old woman with hypertension on
      telmisartan and hydrochlorothiazide, who developed symptomatic hypercalcemia for
      a month. Initial serum calcium was 15.6 mg/dL, together with inappropriately
      elevated intact PTH at 437 pg/mL. Coincidentally, an anterior mediastinal mass on
      chest imaging was found. Biopsy of the mass revealed parathyroid tissue. She was
      treated sequentially with saline rehydration and frusemide calciuresis,
      intravenous pamidronate and calcitonin, which lowered her calcium to 11.1 mg/dL.
      Normocalcemia was finally achieved following surgical extirpation of the mass.
      Histology confirmed an intrathymic parathyroid cyst. Definitive treatment by
      resection of the mass is potentially curative.

PMID- 21881377
TI  - Microscopic sclerosing hemangioma diagnosed by histopathological examination
      after lung cancer surgery.
AB  - A 44-year-old woman underwent surgery for lung cancer. Although preoperative
      computed tomography did not reveal a tiny nodule, pathological examination of the
      background lung showed that type II pneumocyte-like tumor cells grew papillary in
      an area of approximately 2.3 * 1.2 mm. This lesion exhibited hemorrhage,
      hemosiderosis, calcification, and varying degrees of fibrosis, leading to the
      diagnosis of sclerosing hemangioma. This is the first reported case of
      microscopic sclerosing hemangioma undetectable by chest computed tomography.

PMID- 21881378
TI  - Single-stage operation for giant substernal goiter with severe coronary artery
      disease.
AB  - A 76-year-old female, with a history of asthma and tracheal bronchitis, presented
      with a non-ST elevation, myocardial infarction. Chest x-ray on admission showed a
      widened mediastinum, which was further evaluated with a computed tomography (CT)
      scan. It disclosed a giant substernal goiter compressing the trachea and the
      ascending aorta. Cardiac catheterization showed significant coronary disease
      unsuitable for percutaneous intervention; thus, the patient was scheduled for
      coronary artery bypass grafting. Single stage thyroidectomy immediately followed
      by coronary artery bypass was performed. After surgery, her upper airway symptoms
      were improved, and no cardiac events were noted. Collaboration between
      otolaryngology and thoracic surgery teams contributed to good outcomes for this
      patient with substernal goiter and severe cardiac disease.

PMID- 21881379
TI  - Preoperative computed tomographic diagnosis of an aortocaval fistula associated
      with aneurysm of the abdominal aorta.
AB  - Aortocaval fistula is a rare but life-threatening complication of ruptured
      abdominal aortic aneurysm. We present a case of an aortocaval fistula with acute
      right heart failure. The condition was accurately diagnosed before operation by
      physical examination, echo, and especially by computed tomography (CT), thereby
      enabling proper planning of the operative strategy. At surgery, not only the
      infrarenal aorta and common iliac arteries on both sides but the inferior vena
      cava and iliac veins on both sides were also controlled to avoid massive venous
      bleeding through the fistula. Aortocaval fistula repair was easy, and
      conventional bifurcated Dacron graft replacement for abdominal aortic aneurysm
      was successfully performed. Innovative CT images give us prompt preoperative
      diagnoses and elaborate surgical strategies.

PMID- 21881380
TI  - Usefulness of a partial median sternotomy for acute infectious endocarditis in
      patients with tracheostoma.
AB  - Infectious endocarditis patients occasionally need emergency cardiac surgery even
      if they have a tracheostoma. However, a median full-sternotomy approach carries
      increased risk for sternal infection and lethal mediastinitis in cardiac surgery
      for patients with tracheostomas. We successfully performed valve replacement
      procedures using a lower partial median sternotomy approach in 6 infectious
      endocarditis patients with tracheostomas. There were neither operative deaths nor
      complications related to wound infection in these cases. The partial sternotomy
      approach represents a safe alternative in cardiac surgery for acute infectious
      endocarditis patients with tracheostomas who need emergent surgery.

PMID- 21881381
TI  - Successful management of acute necrotizing mediastinitis with trans-cervical
      drainage.
AB  - Acute necrotizing mediastinitis (ANM) is a lethal disease which without
      antibiotic therapy and surgical intervention can lead to about 40% mortality.
      With the development of imaging technology, spiral computed tomography (CT)
      scanning and shortening of the time of diagnosis and surgery, the prognosis of
      these patients is excellently improved. This study describes the clinical
      presentation, management and outcome of 4 patients (mean age: 35 years) with ANM.
      All patients were operated on by a trans-cervical approach, and only one patient
      was operated on by a trans-thoracic one. After surgery, patients were transferred
      to the intensive care unit and underwent daily washing and debridement with
      antibiotic treatments. Odontogenic infection (2 cases), pharyngeal perforation
      and cervical esophageal perforation were the causes of the ANM. Infection of
      cervical space (perivisceral spaces) and superior Mediastinum were found in all
      patients, and Infection below the carina was found in two. All patients were
      discharged with a good, general condition after an average of 24 days. Early
      diagnosis of ANM with clinical presentation and on-time CT scanning, early
      drainage and careful post operation care are very important in the management of
      patients with ANM and can improve the outcome of trans-cervical drainage to an
      acceptable technique.

PMID- 21881382
TI  - Primary ependymoma in the posterior mediastinum.
AB  - A 46-year-old woman was referred to our hospital because of back pain and an
      abnormality on chest imaging. Chest computed tomography showed a well-delineated
      tumor in the left paravertebral space. Histological analysis of the resected
      tumor revealed perivascular pseudorosettes, and immunoreactivity for glial
      fibrillary acidic protein established the diagnosis of ependymoma. A few cases
      have been reported in the ovary, broad ligament, sacrococcygeal region, lungs,
      and mediastinum, but the pathogenesis has not yet been clarified. Female
      predominance in these tumors and organogenesis of the sites may suggest a key to
      the pathogenesis.

PMID- 21881383
TI  - A case of successful valve repair for aortic insufficiency associated with
      discrete subaortic stenosis.
AB  - Discrete subaortic stenosis (DSS) is an uncommon form of left ventricular outflow
      tract obstruction especially in adulthood. Moreover, aortic regurgitation (AR),
      which is a common sequence of DSS, requiring surgical correction is extremely
      rare. We report the case of a 33-year old man who had severe DSS accompanied with
      moderate aortic insufficiency. He underwent successful surgery including relief
      of DSS and aortic valve repair. Although careful follow-up is mandatory for
      recurrent AR and DSS, our approach was thought to be feasible for a young adult
      patient with DSS complicated with AR.

PMID- 21881384
TI  - A hamartoma located in the trachea.
AB  - Hamartoma is rarely found to be localized in the trachea. In the literature, only
      about ten cases have been reported. A 52-year-old male who was being treated for
      asthma for 15 years applied to our hospital with a progressive dyspnea complaint.
      During his physical examination, stridor was heard, after which a computed
      tomography of his chest revealed a tracheal mass. Fiberoptic bronchoscopy
      revealed a mass which obstructed 80% of the tracheal lumen attached to the
      posterior tracheal wall with a broad base. The mass was removed surgically with
      segmentary resection of the trachea. histopathological examination of the lesion
      indicated that it was a hamartoma. Hamartomas can localize in the trachea very
      rarely, causing serious obstruction.

PMID- 21881385
TI  - Papillary fibroelastoma of the aortic valve visualized by 320-slice computed
      tomography: report of a case.
AB  - A 72-year-old man presented with a papillary fibroelastoma on the non-coronary
      cusp of the aortic valve. He was asymptomatic, with a history of hypertension and
      paroxysmal atrial fibrillation. Echocardiography revealed a mobile, round mass
      (13 * 15 mm) on the non-coronary cusp of the aortic valve. Scanning with 320
      slice multi-detector row computed tomography (MDCT) also revealed a mass on the
      non-coronary cusp of the aortic valve. The tumor was subsequently excised from
      the aortic valve. In this case, the MDCT images were extremely clear and provided
      useful information like that obtained with echocardiography.

PMID- 21881386
TI  - Sinus node artery-preserving superior transseptal approach: a simple technique.
AB  - With the use of the superior transseptal approach during mitral valve surgery,
      good exposure of the mitral valve can be achieved with simple traction sutures,
      which minimize the risk of deformation of the mitral valve. For this reason, we
      routinely perform mitral valvoplasty using the superior transseptal approach;
      however, we, occasionally encounter cases that develop postoperative atrial
      dysrhythmia. We have therefore, devised a very simple technique for preservation
      of the sinus node artery in the superior transseptal approach, which is effective
      for reducing the incidence of postoperative sinus node dysfunction. In this
      technique, during incision of the dome of the left atrium, the sinus node artery
      is carefully dissected and preserved.

PMID- 21881387
TI  - Venous thromboembolism prophylaxis after hospital discharge: transition to
      preventive care.
AB  - Deep vein thrombosis and pulmonary embolism, the common clinical manifestations
      of venous thromboembolism (VTE), are among the most preventable complications of
      hospitalized patients. However, survey data repeatedly show poor rates of
      compliance with guideline-based preventive strategies. This has led the Centers
      for Medicare and Medicaid Services to deny reimbursement for hospital readmission
      for thromboembolic complications in patients undergoing total hip or knee
      arthroplasty. Multiple strategies and national initiatives have been developed to
      improve rates of VTE prophylaxis during hospitalization; however, most VTE occurs
      in the outpatient setting. Epidemiologic data suggest that recent surgery or
      hospitalization is a strong risk factor for the development of VTE and that this
      risk may persist for up to 6 months. These observations call into question
      whether VTE prophylaxis should be administered only during hospitalization or if
      this preventive strategy should be continued after hospital discharge. Many of
      the randomized trials showing efficacy of VTE prophylaxis have used longer
      durations of prophylaxis than are typical for current length of hospital stay,
      highlighting the issue of how long the duration of prophylaxis should be. Several
      patient groups have undergone formal testing to evaluate the risks and benefits
      of extended-duration VTE prophylaxis, but this issue is less clear for other
      categories of patients. Although there is clear consensus that most hospitalized
      patients should receive VTE prophylaxis, there is uncertainty about whether to
      continue VTE prophylaxis in the immediate post-hospital period or for an extended
      duration. The transition from inpatient to outpatient care is a key event in the
      coordination of continuity of care, but VTE-specific care transition guidance is
      limited. In this article, we review the evidence for both standard- and extended
      duration VTE prophylaxis and discuss the difficulties in effectively maintaining
      VTE prophylaxis during the transition from inpatient to outpatient care.

PMID- 21881388
TI  - Impact of dyspnea on medical utilization and affiliated costs in patients with
      acute coronary syndrome.
AB  - BACKGROUND: Current clinical practice guidelines recommend dual antiplatelet
      therapy with aspirin and clopidogrel or prasugrel for patients with acute
      coronary syndrome (ACS). Ticagrelor, an experimental antiplatelet therapy, has
      been shown to be associated with significantly higher rates of dyspnea than
      clopidogrel in clinical trials. Patients with ACS presenting with dyspnea require
      additional medical attention to rule out possible heart failure or other serious
      diagnoses. This study used real-world data to quantify the direct medical costs
      of dyspnea among patients with a history of ACS. OBJECTIVE: To determine the
      clinical and economic impact of a dyspnea episode for patients with a history of
      ACS using commercial and Medicare supplemental claims data. METHODS: Patients
      with an emergency room (ER) visit with a primary diagnosis of dyspnea
      (International Classification of Diseases, Ninth Revision, Clinical Modification
      [ICD-9-CM] diagnosis code, 786.0x) in 2008 or 2009 were identified using Thomson
      Reuters MarketScan((r)) Research Databases. Patients were required to have 6
      months of continuous medical enrollment prior to an ER visit and a history of ACS
      (ie, >= 1 inpatient claim, >= 1 ER visit, or >= 2 outpatient claims, with an ICD
      9-CM diagnosis code for ACS [410.xx or 411.1x] in any position on the outpatient
      claim during either the baseline period or on the index date). An episode of
      dyspnea was defined as all ER and outpatient services on the day of an ER claim
      with a primary diagnosis of dyspnea, and any inpatient admissions occurring on
      the day of or day following the ER visit. Procedure utilization and expenditures
      were evaluated for the ER visit and associated outpatient services, as well as
      the proportion of ER visits that led to an inpatient stay. Costs were allowed
      charges (ie, provider payment plus member cost-share) adjusted to 2009 US
      constant dollars. RESULTS: A total of 8433 ER visits for dyspnea were identified
      during 2008 to 2009 from these databases of approximately 74 million
      beneficiaries. The average cost per dyspnea episode was $6958, of which $1621
      were outpatient costs associated with the ER visit (standard deviation, $3269).
      Along with physician services, assessment of dyspnea often included
      electrocardiogram (71.3%), chest radiograph (75.9%), and, occasionally, a B-type
      natriuretic peptide test (14.9%) or chest computed axial tomography scan (12.2%).
      More than one-fourth (25.8%) of dyspnea ER visits preceded an inpatient stay,
      with an average cost of $20 693 per patient. CONCLUSIONS: Dyspnea is a
      significant event associated with high medical resource utilization and hospital
      costs. Ticagrelor, an experimental antiplatelet agent not yet available on the
      market, has been shown to be associated with significantly higher rates of
      dyspnea than clopidogrel in clinical trials. Considering that the increased risk
      of dyspnea for ticagrelor is well documented, these costs may be important to
      health plan decision-makers when evaluating costs associated with each
      antiplatelet therapy.

PMID- 21881389
TI  - Hospital-based clinical implications of the novel oral anticoagulant, dabigatran
      etexilate, in daily practice.
AB  - Dabigatran etexilate is an oral direct thrombin inhibitor that has been approved
      by the US Food and Drug Administration for the prevention of stroke and systemic
      embolization in patients with nonvalvular atrial fibrillation. It has also been
      studied for the prevention of venous thromboembolism in patients after hip and
      knee arthroplasty and for treatment of venous thromboembolism. Although routine
      laboratory monitoring is not needed, there are clinical scenarios in which
      physicians will need to have a clear understanding of drug pharmacology,
      laboratory assessment, and reversibility of this drug to make appropriate
      clinical decisions. We review the pharmacology of dabigatran etexilate, pertinent
      clinical trials, and the effects of dabigatran etexilate on prothrombin time,
      activated partial thromboplastin time, thrombin time, and ecarin clotting time.
      We also provide an approach to patients on dabigatran etexilate who are bleeding,
      have a suspected therapeutic failure, or require periprocedural management.

PMID- 21881390
TI  - Protecting the heart from ischemia: an update on ischemic and pharmacologic
      conditioning.
AB  - The attempt to find treatments that will reduce myocardial cell death during
      periods of ischemia and subsequent reperfusion has spanned nearly 40 years.
      Although many therapies have shown promise in animal models, relatively few have
      been successful in clinical trials. Some of the most effective clinical therapies
      involve techniques designed to elicit the heart's own innate capacity to protect
      itself. The ability of the heart to render itself more resistant to
      ischemia/reperfusion injury was not appreciated until the description of ischemic
      preconditioning in 1986. Following the discovery that brief, nonlethal episodes
      of ischemia conditioned the heart to better tolerate a subsequent prolonged
      episode of ischemia, alternative ways of evoking this endogenous cardioprotection
      were described. Ischemic postconditioning and remote conditioning are potentially
      useful tools for protecting ischemic myocardium, and have been shown to be
      beneficial in small clinical trials. Several pharmacologic agents have the
      ability to mimic the effects of ischemic conditioning and can also reduce the
      amount of cell death during ischemia/reperfusion. This article provides the
      clinician with an overview of the different techniques of ischemic conditioning
      and how they can protect the myocardium from ischemia/reperfusion injury.
      Additionally, several pharmacologic agents that can protect the heart in a
      similar manner are discussed.

PMID- 21881391
TI  - Adequacy of chest compressions performed by medical housestaff.
AB  - BACKGROUND: Chest compressions (CCs) are a critical part of cardiopulmonary
      resuscitation. We studied the presence and duration of adequate CCs performed by
      medical housestaff, and correlated our findings with gender and body mass index.
      METHODS: Fifty-eight first-postgraduate-year medical housestaff performed CCs on
      a computerized patient simulator equipped with a calibrated CC measurement
      device. Following initial testing, subjects were trained to perform adequate CCs.
      Subjects were retested 2 weeks later. Presence and duration of adequate CCs were
      measured during a 120-second endurance test. RESULTS: Before training, 14/28
      (50%) of the male housestaff performed adequate CCs and 0/30 (0%) of the female
      housestaff performed adequate CCs. After training, 25/28 (89%) of the male
      housestaff and 16/30 (53%) of the female housestaff performed adequate CCs. Body
      mass index and height were not related to adequacy of CCs. After training, 7/28
      (25%) of the male subjects and 1/30 (3%) of the female subjects were able to
      maintain adequate CCs for 120 seconds. CONCLUSIONS: Training housestaff on a
      patient simulator is an effective means of improving the adequacy of CCs. Despite
      training, a significant number of women were unable to perform adequate CCs
      compared with men; body mass index and height were not determining factors. Very
      few housestaff were able to sustain 120 seconds of adequate CCs, despite
      training.

PMID- 21881392
TI  - Evaluation and management of chronic pulmonary thromboembolic disease.
AB  - Pulmonary embolism (PE) is common and the majority of patients survive the acute
      event. Survivors are at increased risk for adverse outcomes, including persistent
      thrombi, recurrent embolism, chronic thromboembolic pulmonary hypertension
      (CTEPH), and death. Anticoagulation protects against recurrence, which has a high
      mortality rate. The recommended duration of anticoagulation for patients with
      reversible PE risk factors is 3 months. For patients with idiopathic PE or
      persistent risk factors, extended duration of anticoagulation is preferred,
      balanced with an individual patient's risk of hemorrhage, which in itself is a
      major cause of morbidity and mortality. Among patients with malignancy who
      develop venous thromboembolism (VTE), low-molecular-weight heparin is preferred
      over oral vitamin K antagonists in the first 6 months. Thereafter,
      anticoagulation should be continued indefinitely with either low-molecular-weight
      heparin or oral vitamin K antagonists. Inferior vena cava filters are not
      routinely recommended and should only be used in patients who have a
      contraindication to anticoagulation. Patients who have had VTE and with
      persistent or recurrent dyspnea should be evaluated for recurrence of VTE or
      development of CTEPH. Patients with recurrent VTE should be anticoagulated
      indefinitely. Routine screening for CTEPH in asymptomatic patients is not
      recommended. Echocardiography often provides the first indication of the presence
      of pulmonary hypertension. Once presence of CTEPH is established by right-sided
      heart catheterization and perfusion imaging (ie, ventilation/perfusion
      scintigraphy, computed tomography angiography, or pulmonary angiography),
      patients should be referred early to a center with expertise, as it is
      potentially surgically curable by pulmonary endarterectomy. Those who are deemed
      inoperable after being evaluated may gain symptomatic benefit from drugs approved
      for idiopathic pulmonary arterial hypertension. Lung transplantation may also be
      an option for patients who are not candidates for pulmonary endarterectomy.

PMID- 21881393
TI  - Carotid angioplasty and stenting: evolution and current status.
AB  - The management of carotid stenosis is in evolution. Carotid endarterectomy has
      been the gold standard for the treatment of carotid stenosis for many years.
      However, recently, carotid angioplasty and stenting has emerged as a feasible and
      relatively safe management alternative. The appropriate clinical setting for its
      preferential use over carotid endarterectomy continues to be the subject of
      ongoing clinical trials. In this article, we review the evolution of carotid
      angioplasty and stenting, the evidence behind the current indications, and
      limitations of this procedure, as well as provide an overview of preprocedural
      evaluations and periprocedural management.

PMID- 21881394
TI  - Inferior vena cava filters: a concise review.
AB  - Venous thromboembolic disease is associated with significant morbidity and
      mortality. Anticoagulation has been the mainstay of treatment and prevention.
      Unfortunately, anticoagulation frequently fails or is contraindicated. Use of
      inferior vena cava filters can be an effective alternative in these scenarios.
      Though inferior vena cava filters have been used for > 4 decades, the evidence
      behind their use is limited. Use of IVC filters is associated with both minor and
      major complications. More randomized prospective trials are needed to evaluate
      these devices. In this article, we review issues concerning the use of inferior
      vena cava filters.

PMID- 21881395
TI  - Inferior vena cava filter thrombosis: a review of current concepts, evidence, and
      approach to management.
AB  - The increased risk of venous thrombosis within and below the inferior vena cava
      (IVC) is the main long-term complication of IVC filter placement. In this
      article, we discuss current concepts regarding the incidence, risks, and
      management of IVC filter thrombosis. Evidence of the association of each of the
      following factors is reviewed: type and design of the filter device, population
      demographics, underlying hypercoagulable states/anticoagulation, modality used to
      assess for thrombosis, and length of time elapsed since filter placement. Certain
      double-basket filter designs and a hypercoagulable state are associated with
      increased incidence of IVC filter thrombosis. Most cases of IVC filter thrombosis
      are asymptomatic. While large series data on the use of magnetic resonance
      imaging for the detection of filter thrombosis remain unavailable, evidence
      suggests that contrast-enhanced computed tomography is preferable to Doppler
      sonography. A proposed algorithm for the management of IVC filter thrombosis is
      provided.

PMID- 21881396
TI  - Hyponatremia in hospitalized patients: the potential role of tolvaptan.
AB  - Hyponatremia (typically defined as serum sodium level < 135 mEq/L) is a common
      electrolyte abnormality among hospitalized patients. Whether present at admission
      or acquired during hospitalization, hyponatremia is associated with higher
      mortality and longer hospital stays. Failure to adequately investigate and treat
      hyponatremia may also be associated with adverse outcomes. The presence and
      severity of clinical symptoms largely depend on the rate and extent of the
      decline in serum sodium; rapid or large decreases may cause serious neurologic
      complications. The approach to treatment depends on the presence and severity of
      symptoms, the timing of their onset, the underlying etiology, and the patient's
      volume status. Patients with euvolemic or hypervolemic hyponatremia usually have
      inappropriately elevated levels of arginine vasopressin, which stimulates water
      reabsorption even in the presence of low serum osmolality. Tolvaptan is an orally
      active, selective V2-receptor antagonist that blocks the effects of arginine
      vasopressin in the renal collecting duct to promote aquaresis without increasing
      sodium or potassium excretion; as a result, it increases serum sodium in a
      controlled manner. Tolvaptan offers a mechanism-based treatment option for
      patients with euvolemic or hypervolemic hyponatremia who have serum sodium levels
      < 125 mEq/L or persistent symptoms resistant to fluid restriction.

PMID- 21881397
TI  - Sepsis: the inflammatory foundation of pathophysiology and therapy.
AB  - Sepsis, defined as an infection accompanied by inflammation, is a complex disease
      process wherein the body's response to a pathogen is amplified far beyond the
      initial site of infection. The process begins when pathogen-associated molecular
      patterns on the bacteria or other pathogens induce an inflammatory cascade in the
      host. In the United States, it is estimated that every minute a patient with
      severe sepsis or septic shock presents to an emergency department and that > 751
      000 cases of severe sepsis occur annually, resulting in an estimated 215 000
      deaths. A rapid progression of illness severity from sepsis to severe sepsis to
      septic shock frequently occurs, driven by the body's inflammatory and anti
      inflammatory responses to a pathogen, making sepsis a condition requiring timely
      intervention. The clinical management of severe sepsis and septic shock has
      evolved dramatically over the past decade and these new therapeutic approaches
      have been built on a deeper understanding of the natural evolution of sepsis.
      This article examines the underlying pathophysiological mechanisms of sepsis to
      help explain the clinical signs and symptoms manifested by severe sepsis
      patients. It also examines the significance of current proposed treatment
      strategies, including early goal-directed therapy, from a pathophysiological and
      inflammatory perspective.

PMID- 21881398
TI  - Impact of intelligent intravenous infusion pumps on directing care toward
      evidence-based standards: a retrospective data analysis.
AB  - INTRODUCTION: Published literature has successfully demonstrated the impact of
      intravenous (IV) infusion pump safety software on improving the quality of health
      care delivery. Much of this literature has focused solely on the ability of these
      devices to prevent potential medication errors, while overlooking the devices'
      additional valuable advantages. One non-reported benefit is the ability of IV
      infusion pump safety software to consistently administer doses of IV medication,
      which are based on evidence. This article describes the process undertaken to
      implement and evaluate the impact of IV infusion pump safety software on driving
      care toward evidence-based standards. METHODS: An advisory group of expert users
      was convened for a 2-day session to develop consensus recommendations of best
      practices for IV infusion pump safety software. Using these recommendations,
      administrative data were collected from a community hospital to assess the
      endpoints identified by the advisory panel. RESULTS: Data analysis of rescue
      agents (ie, flumazenil, glucagon, and protamine sulfate) showed reductions in
      utilization in the post-implementation period of the safety software. The
      decreased requirement for blood transfusions in patients receiving heparin
      infusions suggests that heparin infusions were more safely administered in the
      post-implementation period. The decreased length of stay and mortality rate
      observed in patients with complex respiratory infections during the post
      implementation period suggests that by correctly infusing antibiotics
      consistently, patient outcomes may be improved. Additionally, alert and edit data
      from the pumps demonstrated that the IV infusion pump safety software alerted to
      and influenced edits on many critical dose rate errors for benzodiazepines,
      heparin, and several antibiotics. CONCLUSION: Intravenous infusion pump safety
      software improves clinical outcomes through consistent application of evidence
      based standards of dose rates for IV drugs.

PMID- 21881399
TI  - Design and implementation of a low-cost multimodal procedure cart for an internal
      medicine ward.
AB  - INTRODUCTION: General internists perform a large number and variety of procedures
      in the ward and emergency department settings. Initiatives are needed to
      facilitate learning and increase efficiency of procedural skill acquisition by
      trainees. In this article, we describe our experience developing and implementing
      a low-cost multimodal procedure cart in an academic health sciences center. We
      also provide pilot data on perceived usefulness by trainees. METHODS: We
      performed a needs-assessment survey of residents, which indicated that the
      inconsistent location of materials and time needed to gather them were
      frustrating. Furthermore, residents reported that having easily accessible
      educational materials would improve their experience performing procedures. Based
      on this information, a portable cart was designed and implemented that had all
      materials required for common ward procedures, as well as multimodal educational
      materials, including evidence-based checklists, a hard-copy procedure manual, and
      a portable computer for viewing videos and logging procedures. The cart was
      equipped for the most commonly performed bedside procedures. After 2 months, we
      electronically surveyed residents on their experience with the intervention.
      Measures included self-reported frequency of use, satisfaction, perceived
      improvement in efficiency, and perceived improvement in patient safety. RESULTS:
      Residents perceived that the cart increased efficiency. The ready availability of
      educational materials was also noted as an advantage. Despite its perceived
      usefulness, trainees did not use the cart as frequently as anticipated. The cart
      continues to be in use > 1 year later, with modifications made based on feedback.
      CONCLUSIONS: In this article, we outline suggestions for successful
      implementation of a similar initiative based on our experience. We describe how a
      procedure cart can be inexpensively designed and instituted to facilitate more
      efficient performance of medical procedures and enhance education. Such an
      intervention may be beneficial in an academic as well as a community setting.

PMID- 21881400
TI  - Care transitions from inpatient to outpatient settings: ongoing challenges and
      emerging best practices.
AB  - Care transitions occur every time a patient changes levels of service, location,
      or with each shift change or transfer of care. The complexities involved in
      transitions of care make these time periods particularly susceptible to medical
      errors, placing patients at risk. Improving care transitions affects all patients
      in all settings, and has the potential to reduce adverse events, improve quality
      of care, and produce medical cost savings. This article is a focused review of
      transitions in care from the inpatient to ambulatory care settings. Underlying
      challenges and sources of errors are identified, and possible solutions and
      interventions are explored. Specific challenges to the pediatric population are
      also examined in detail.

PMID- 21881401
TI  - Accountable Care Organizations: roles and opportunities for hospitals.
AB  - Federal health reform has established Medicare Accountable Care Organizations
      (ACOs) as a new program, and some states and private payers have been
      independently developing ACO pilot projects. The objective is to hold provider
      groups accountable for the quality and cost of care to a population. The
      financial models for providers generally build off of shared savings between the
      payers and providers or some type of global payment that includes the possibility
      of partial or full capitation. For ACOs to achieve the same outcomes with lower
      costs or, better yet, improved outcomes with the same or lower costs, the
      delivery system will need to become more oriented toward primary care and care
      coordination than is currently the case. Providers of clinical services, in order
      to be more effective, efficient, and coordinated, will need to be supported by a
      variety of shared services, such as off-hours care, easy access to specialties,
      and information exchanges. These services can be organized by an ACO as a medical
      neighborhood or community. Hospitals, because they have a management structure,
      history of developing programs and services, and accessibility 24/7/365, are
      logical leaders of this enhancement of health care delivery for populations and
      other providers.

PMID- 21881403
TI  - Tracheostomy care: a clinician's guide.
AB  - Tracheostomies have become a typical component of the management of patients with
      prolonged respiratory failure. There are, however, relatively few studies from
      which to establish an accepted standard of care with regard to the specific
      features, daily care, and removal of tracheostomy tubes. Consequently, these
      decisions are sometimes guided by myth and misconception. In this article, we
      review the different types of tracheostomy tubes with their respective advantages
      and disadvantages, basic principles of care, recognition of complications, speech
      with a tracheostomy tube, and the process by which they may sometimes be removed.

PMID- 21881402
TI  - Nuclear medicine imaging in dementia: a practical overview for hospitalists.
AB  - Dementia is a clinical syndrome with diverse presentation, a challenging
      differential diagnosis, and time-sensitive therapy. The most common cause of
      dementia in patients aged > 65 years is Alzheimer's disease, which now affects 4
      million people in the United States, but is often underrecognized, especially in
      the inpatient population. The hospitalist may have the opportunity to evaluate a
      patient's initial presentation of dementia. Addressing the inpatient's dementia
      symptoms can improve overall care and outcomes, so it is imperative that the
      hospitalist is abreast of recent developments in the dementia workup. The focus
      of this article is to overview how nuclear medicine imaging of the brain can aid
      in this process, with perfusion single-photon emission computed tomography
      (SPECT) and fludeoxyglucose F 18 ((18)F-FDG) positron emission tomography (PET)
      as the 2 most common modalities. Our discussion focuses on Alzheimer's disease,
      as this the most common etiology of dementia in patients aged > 65 years;
      however, we also touch on the other common neurodegenerative dementias (eg,
      dementia with Lewy bodies, vascular dementia, and frontotemporal dementia) for
      completeness. We begin with a summary of the most recent published guidelines for
      each of these neurodegenerative diseases, and then expand on the role that
      nuclear imaging plays in each. We provide a basic overview of the principles of
      these nuclear medicine techniques, and then illustrate findings in perfusion
      SPECT and (18)F-FDG PET for typical patterns of dementia, with emphasis on
      evidence regarding diagnostic accuracy of each modality, in comparison with
      accepted gold standards. Finally, we outline some future research topics within
      the field of nuclear medicine in dementia, including amyloid plaque imaging and
      dopamine transporter imaging.

PMID- 21881404
TI  - A case-based approach to noninvasive positive pressure ventilation.
AB  - Noninvasive positive pressure ventilation (NIPPV) has revolutionized the concept
      of mechanical ventilation with the major benefit of avoiding invasive mechanical
      ventilation in specific situations, thereby preventing associated complications.
      Noninvasive positive pressure ventilation has emerged as the first line of
      management of hypercapnic respiratory failure (due to chronic obstructive
      pulmonary disease and neuromuscular weakness) and cardiogenic pulmonary edema in
      addition to standard therapy in the acute setting. There is improvement in gas
      exchange, relief of respiratory muscle fatigue, and clinical outcome with reduced
      morbidity and mortality. Nevertheless, contraindications and failures need to be
      identified early, as delaying endotracheal intubation is associated with
      increased morbidity and mortality. Despite overwhelming evidence to support its
      use, NIPPV is underused. Residents and hospitalists need to identify NIPPV as a
      treatment option in acute respiratory failure.

PMID- 21881405
TI  - Analyzing RNA polymerase III by electron cryomicroscopy.
AB  - Recent electron cryomicroscopy reconstructions have provided new insights into
      the overall organization of yeast RNA polymerase (Pol) III, responsible for the
      synthesis of small, non-translated RNAs. The structure of the free Pol III enzyme
      at 10 A resolution provides an accurate framework to better understand its
      overall architecture and the structural organization and functional role of two
      Pol III-specific subcomplexes. Cryo-EM structures of elongating Pol III bound to
      DNA/RNA scaffolds show the rearrangement of the Pol III-specific subcomplexes
      that enclose incoming DNA. In one reconstruction downstream DNA and newly
      transcribed RNA can be followed over considerably longer distances as in the
      crystal structure of elongating Pol II. The Pol III transcription machinery is
      increasingly recognized as a possible target for cancer therapy. The recent cryo
      EM reconstructions contribute to the molecular understanding of Pol III
      transcription as a prerequisite for targeting its components.

PMID- 21881406
TI  - mirExplorer: detecting microRNAs from genome and next generation sequencing data
      using the AdaBoost method with transition probability matrix and combined
      features.
AB  - microRNAs (miRNAs) represent an abundant group of small regulatory non-coding
      RNAs in eukaryotes. The emergence of Next-generation sequencing (NGS)
      technologies has allowed the systematic detection of small RNAs (sRNAs) and de
      novo sequencing of genomes quickly and with low cost. As a result, there is an
      increased need to develop fast miRNA prediction tools to annotate miRNAs from
      various organisms with a high level of accuracy, using the genome sequence or the
      NGS data. Several miRNA predictors have been proposed to achieve this purpose.
      However, the accuracy and fitness for multiple species of existing predictors
      needed to be improved. Here, we present a novel prediction tool called
      mirExplorer, which is based on an integrated adaptive boosting method and
      contains two modules. The first module named mirExplorer-genome was designed to
      de novo predict pre-miRNAs from genome, and the second module named mirExplorer
      NGS was used to discover miRNAs from NGS data. A set of novel features of pre
      miRNA secondary structure and miRNA biogenesis has been extracted to distinguish
      real pre-miRNAs from pseudo ones. We used outer-ten-fold cross-validation to
      verify the mirExplorer-genome computation, which obtained a specificity of 95.03%
      and a sensitivity of 93.71% on human data. This computation was made on test data
      from 16 species, and it achieved an overall accuracy of 95.53%. Systematic outer
      ten-fold cross-validation of the mirExplorer-NGS model achieved a specificity of
      98.3% and a sensitivity of 97.72%. We found that the good performance of the
      mirExplorer-NGS model was upheld across species from vertebrates to plants in
      test datasets. The mirExplorer is available as both web server and software
      package at http://biocenter.sysu.edu.cn/mir/.

PMID- 21881407
TI  - Two covariance models for iron-responsive elements.
AB  - Iron-responsive elements (IREs) function in the 5' or 3' untranslated regions
      (UTRs) of mRNAs as post-transcriptional structured cis-acting RNA regulatory
      elements. One known functional mechanism is the binding of Iron Regulatory
      Proteins (IRPs) to 5' UTR IREs, reducing translation rates at low iron levels.
      Another known mechanism is IRPs binding to 3' UTR IREs in other mRNAs, increasing
      RNA stability. Experimentally proven elements are quite small, have some
      diversity of sequence and structure, and functional genes have similar
      pseudogenes in the genome. This paper presents two new IRE covariance models,
      comprising a new IRE clan in the RFAM database to encompass this variation
      without over-generalisation. Two IRE models rather than a single model is
      consistent with experimentally proven structures and predictions. All of the IREs
      with experimental support are modelled. These two new models show a marked
      increase in the sensitivity and specificity in detection of known iron-responsive
      elements and ability to predict novel IREs.

PMID- 21881409
TI  - The oncogenic RNA-binding protein Musashi1 is regulated by tumor suppressor
      miRNAs.
AB  - Musashi1 (Msi1) is an evolutionarily conserved RNA-binding protein that has been
      implicated in processes like stem cell fate, nervous system development, and
      tumorigenesis via its activities as a specific regulator of translation. While
      Msi1 is barely detected in normal adult tissue, it has been observed to be highly
      expressed in numerous tumor types (e.g. breast, colon, medulloblastoma,
      glioblastoma, and et cetera). Unfortunately, the molecular cues that are
      responsible for Msi1 upregulation in cancer cells are largely unknown. Tumor
      suppressor microRNAs (miRNAs) are known for targeting genes with oncogenic
      properties like Msi1 and for being either downregulated or deleted in tumor
      tissue. We observed that Msi1 long 3'UTR region is potentially targeted by
      several tumor suppressor miRNAs (miR-34a, -101, -128, -137, and -138). Western
      blotting of endogenous Msi1 protein as well as luciferase assays confirmed Msi1
      regulation by these tumor suppressor miRNAs. Furthermore, we observed when
      examining different cellular states that these miRNAs and Msi1 have opposite
      expression profiles. Cell proliferation inhibition induced by the tumor
      suppressor miRNAs was partially rescued by Msi1 transgenic expression. We
      conclude that tumor suppressor miRNAs are direct and influential regulators of
      Msi1, affecting its expression pattern during tumorigenesis of malignant nervous
      system tumors.

PMID- 21881410
TI  - In vivo and in vitro analysis of 6S RNA-templated short transcripts in Bacillus
      subtilis.
AB  - By differential high-throughput RNA sequencing (dRNA-seq) we have identified
      "product RNAs" (pRNAs) as short as 8-12 nucleotides that are synthesized by
      Bacillus subtilis RNA polymerase (RNAP) in vivo using the regulatory 6S-1 RNA as
      template. The dRNA-seq data were confirmed by in vitro transcription experiments
      and Northern blotting. In our libraries, we were unable to detect statistically
      meaningful numbers of reads potentially representing pRNAs derived from 6S-2 RNA.
      However, pRNAs could be synthesized in vitro from 6S-2 RNA as template by the B.
      subtilis sigma(A) RNAP. 6S-1 pRNA levels are low during exponential, increase in
      stationary, and burst during outgrowth from stationary phase, demonstrating that
      pRNA synthesis is a conserved regulatory mechanism, but a more dynamic and fine
      tuning process than previously thought. Most pRNAs have a length of 8-15 nt, very
      few up to 24 nt. The average length of pRNAs tended to increase from stationary
      to outgrowth conditions. Synthesis of pRNA is initiated at C40 of 6S-1 RNA and
      U41 of 6S-2 RNA, yielding pRNAs with a 5'-terminal G or A residue, respectively.
      A B. subtilis 6S-1 RNA mutant strain encoding a pRNA with a 5'-terminal A residue
      showed the same relative distribution of ~14-nt pRNAs between the different
      growth states, but generally displayed lower pRNA levels than the reference
      strain encoding wild-type 6S-1 RNA. A ~two-fold lower affinity of the C40U mutant
      6S-1 RNA towards sigma(A) RNAP may have contributed to this reduction in pRNA
      levels. We infer that 6S-1 pRNA synthesis, although evolutionarily optimized for
      initiation with a +1G residue, is not primarily regulated at the transcription
      initiation level via growth phase-dependent variations in the cellular GTP pool.

PMID- 21881408
TI  - The structure of human cleavage factor I(m) hints at functions beyond UGUA
      specific RNA binding: a role in alternative polyadenylation and a potential link
      to 5' capping and splicing.
AB  - 3'-end cleavage and subsequent polyadenylation are critical steps in mRNA
      maturation. The precise location where cleavage occurs (referred to as poly(A)
      site) is determined by a tripartite mechanism in which a A(A/U)UAAA hexamer, GU
      rich downstream element and UGUA upstream element are recognized by the cleavage
      and polyadenylation factor (CPSF), cleavage stimulation factor (CstF) and
      cleavage factor I(m) (CFI(m)), respectively. CFI(m) is composed of a smaller 25
      kDa subunit (CFI(m)25) and a larger 59, 68 or 72 kDa subunit. CFI(m)68 interacts
      with CFI(m)25 through its N-terminal RNA recognition motif (RRM). We recently
      solved the crystal structures of CFI(m)25 bound to RNA and of a complex of
      CFI(m)25, the RRM domain of CFI(m)68 and RNA. Our study illustrated the molecular
      basis for UGUA recognition by the CFI(m) complex, suggested a possible mechanism
      for CFI(m) mediated alternative polyadenylation, and revealed potential links
      between CFI(m) and other mRNA processing factors, such as the 20 kDa subunit of
      the cap binding protein (CBP20), and the splicing regulator U2AF65.

PMID- 21881411
TI  - The miR-10 microRNA precursor family.
AB  - The miR-10 microRNA precursor family encodes a group of short non-coding RNAs
      involved in gene regulation. The miR-10 family is highly conserved and has
      sparked the interest of many research groups because of the genomic localization
      in the vicinity of, coexpression with and regulation of the Hox gene
      developmental regulators. Here, we review the current knowledge of the evolution,
      physiological function and involvement in cancer of this family of microRNAs.

PMID- 21881412
TI  - Revisiting the function of nuclear scaffold/matrix binding proteins in X
      chromosome inactivation.
AB  - Mammalian females repress gene expression from one of their two X chromosomes to
      compensate for the gene dosage difference between females and males, via a
      process called X chromosome inactivation (XCI). Since the first discovery of XCI
      50 years ago, the knowledge of this phenomenon has greatly contributed to a
      better understanding of the molecular mechanism that controls the epigenetic
      regulation of gene expression. The key molecule that organizes the chromatin
      level repression is an X-linked 17-kb non-coding RNA named Xist. The transcripts
      of Xist are localized along the entire length of the X chromosome and
      subsequently recruit a chromatin remodeling complex that introduces the
      repressive epigenetic modifications. In the present review, we will highlight the
      recent findings that have illustrated the close relationship between XCI and the
      structural component of the nucleus called the nuclear scaffold/matrix, with an
      emphasis on the function of the bona-fide scaffold/matrix-binding protein hnRNP
      U/SAF-A.

PMID- 21881415
TI  - Developing a family-based diabetes program for Latino immigrants: do men and
      women face the same barriers?
AB  - This study examined barriers and facilitators to diabetes self-management among
      Latino immigrants with diabetes and whether similarities and differences were
      observed by gender. Eight focus groups were conducted with 24 women and 21 men
      Latinos; four focus groups involved women only and four involved men only. Themes
      were identified using a combined deductive/inductive approach and an iterative
      process of consensus coding. Gender similarities and differences emerged.
      Barriers to self-management were primarily social for the women, whereas for men,
      structural aspects related to work were prominent. Interventions aimed at
      improving diabetes self-management among US Latino immigrants should consider
      tailored approaches to help men and women overcome distinct barriers.

PMID- 21881416
TI  - Attitudes, concerns, and likelihood for action related to young children's
      overweight among early childhood program staff.
AB  - For obesity prevention planning in early childhood programs, attitudes and
      actions of staff related to communicating with parents about young children's
      eating and weight need to be assessed. Early childhood program teachers (n = 271)
      working with children aged 3 to 5 years were surveyed by mail. Factor analysis
      provided patterns of response for multi-item questions. Respondents reported
      different levels of agreement and comfort regarding communicating concerns to
      parents about their child's weight and eating versus observations about the
      child's daily eating. Feelings about parent communication varied (worried,
      hesitant, responsible, and willing). Findings suggest opportunities for
      communication between program staff and parents.

PMID- 21881417
TI  - Knowledge, attitudes, and beliefs about nutrition and childhood overweight among
      WIC participants.
AB  - This study assessed knowledge, attitudes, and beliefs about nutrition, physical
      activity, and health risks related to childhood overweight among Women, Infants,
      and Children participants. Most (n = 165) were knowledgeable about causes/health
      risks of overweight (90%). The belief that "some people are born big or thin . .
      . " varied by education level (P < 0.05). Concerning activity, many (white non
      Hispanic, 53%; African-American 69%) reported their children spending 2 to 3
      hours per day watching television and playing video games, with 10% white non
      Hispanic and 21% of African-American reporting 4 hours or more (P < 0.05).
      Beliefs related to the risk of overweight and activity level of the children
      differed among ethnic groups.

PMID- 21881418
TI  - Engaging community-based veterans' organizations in health promotion programs.
AB  - Community organizations, such as churches, clubs, and senior centers, can be
      important locations for health programs. However, little is known about the
      organizational factors that influence participation and engagement in health
      programs. To learn more, we evaluated a community-based program designed to help
      US military veterans better manage their high blood pressure. The program
      involved training a pair of veterans to deliver health-related presentations at
      their local units. We found that factors such as larger meeting attendance size,
      rural location, age diversity, and member enthusiasm were positively associated
      with both a willingness to participate and a high level of engagement in program
      activities.

PMID- 21881419
TI  - Employing a youth-led adult-guided framework: "Why Drive High?" social marketing
      campaign.
AB  - The "Drugged Driving Kills project: Why Drive High?" social marketing campaign
      was developed and implemented by youth leaders and adult facilitators from public
      and community health to increase youth awareness of the adverse effects of
      marijuana on driving. The youth-led adult-guided project was founded on the
      Holden's youth empowerment conceptual model. This article reports on the results
      of the focus group evaluation, conducted to determine to what extent the tailored
      youth-led adult-guided framework for the "Why Drive High?" social marketing
      campaign provided an environment for youth leadership development.

PMID- 21881420
TI  - Health-related quality of life profiles among family caregivers of patients with
      schizophrenia.
AB  - This cross-sectional study aims to determine and compare health-related quality
      of life profiles of schizophrenia family caregivers on the basis of their
      sociodemographic characteristics. Thirty outpatient family caregivers completed
      the generic 36-Item Short Form Health Survey instrument (male = 53.5%; mean age =
      51 years; married = 76.7%). The highest mean score was reported for social
      functioning while role limitation-emotional was rated the worst. Significantly
      better health-related quality of life profiles were demonstrated by caregivers
      who were male, younger than 50 years, adequately educated, employed, and without
      health problems and were receiving monthly income. Understanding of on health
      related quality of life matters for family caregivers is crucial to improve the
      quality of care for schizophrenia patients.

PMID- 21881421
TI  - Starting over from scratch: social support and youth coping with internal
      displacement.
AB  - This article presents findings from a qualitative research study with daughters
      of internally displaced families, more than a decade and half after the end of
      the Lebanese civil war. In-depth interviews with these adolescent girls indicate
      that in the absence of universal coverage of social security nets for the
      Lebanese, the effects of impoverishment and continuous mobility in the suburbs
      have adverse effects on their sense of stability, schooling, and coping. The
      article argues that although the effects of impoverishment are not new to similar
      urban youth populations, the quality of social support networks (ties to rural
      areas and support from welfare agency services) is a determining factor in the
      way they cope with adversity. Implications for policy are also presented.

PMID- 21881422
TI  - Nonmedical healing methods: knowledge and behavior among parents of children with
      mental health problems.
AB  - This study examined knowledge and behavior concerning nonmedical healing methods
      used by parents whose children present with mental health problems and to
      determine the factors affecting this behavior. Knowledge of a variety of
      nonmedical health methods was found to be more common than use of such methods.
      Among those expressing knowledge of such methods, religious procedures were found
      to be more common than those that are nutrition related. Also, nonmedical healing
      method use increased as the mother's age decreased. We found a significant
      relationship between nonmedical healing method--using behavior and a positive
      family history of nonmedical healing method usage. Education about mental health
      problems and their treatment is very important, especially for young mothers.
      Increased understanding about nonmedical healing methods among health care
      providers will improve the patient-family-provider relationship.

PMID- 21881426
TI  - My call to action: the hidden problem of urinary incontinence: you can make a
      difference!

PMID- 21881427
TI  - The intersection of the Medicare end-stage renal disease (ESRD) benefit and
      hospice: an overview for home care and hospice clinicians.
AB  - End-of-life care is underutilized in patients with kidney failure despite high
      mortality and multiple comorbid conditions. Recent revisions in the Medicare
      Benefit Policy Manual and the Conditions for Coverage for End-Stage Renal Disease
      provide a clearer understanding for referral to palliative and hospice care.
      There are recommendations to improve end-of-life care in this complicated
      population.

PMID- 21881431
TI  - The pediatric renal transplant process: a guide for home health clinicians.
AB  - Kidneys are one of the most commonly transplanted solid organs in children. In
      2008, 16,067 renal transplants were performed in the United States; of those, 773
      were performed on patients under the age of 18 (2009 OPTN/SRTR Annual Report 1999
      2008, 2009). The process of renal transplantation can be a long one and children
      and their families often endure many challenges on the road to the transplant,
      not to mention the adjustments that lie ahead afterward. For this reason, and
      because these patients benefit from home health follow-up after their transplant,
      it is important for home health clinicians to be knowledgeable about the renal
      transplant process in addition to posttransplant care.

PMID- 21881433
TI  - Understanding the physical therapy evaluation in home healthcare: practical
      pointers for the nurse clinical record reviewer.
AB  - Nurses are often called upon to audit therapy documentation but may struggle to
      interpret the "language" of other disciplines and apply Medicare's coverage
      guidelines for appropriate, reasonable, and necessary services. This article
      seeks to provide the nurse reviewer with insight into the most critical aspect of
      establishing medical necessity for physical therapy services, the initial patient
      evaluation.

PMID- 21881429
TI  - Depression Care for Patients at Home (Depression CAREPATH): home care depression
      care management protocol, part 2.
AB  - High levels of depressive symptoms are common and contribute to poorer clinical
      outcomes even in geriatric patients who are already taking antidepressant
      medication. The Depression CARE for PATients at Home (Depression CAREPATH)
      intervention was designed to meet the needs of medical and surgical patients who
      suffer from depression. The intervention's clinical protocols are designed to
      guide clinicians in managing depression as part of routine home care.

PMID- 21881434
TI  - Healthcare reform and vulnerable home health patients: building the case for a
      stronger safety net.

PMID- 21881435
TI  - The International Home Care Nurses Organization (IHCNO) goes global.

PMID- 21881436
TI  - Selecting the best design team partners.
AB  - Choosing the right design partner is a critical step in planning a new hospital,
      new addition or in remodeling an existing facility. This facility design
      department aims to expand nurse leaders' knowledge and competencies in health
      facility design and enables them to take leadership roles in design efforts. This
      article focuses on the nurse leaders' role in selecting the best possible design
      partner to ensure a collaborative working relationship throughout the project.

PMID- 21881437
TI  - Improving processes through evolutionary optimization.
AB  - As systems evolve over time, their natural tendency is to become increasingly
      more complex. Studies on complex systems have generated new perspectives on
      management in social organizations such as hospitals. Much of this research
      appears as a natural extension of the cross-disciplinary field of systems theory.
      This is the 18th in a series of articles applying complex systems science to the
      traditional management concepts of planning, organizing, directing, coordinating,
      and controlling. In this article, I discuss methods to optimize complex
      healthcare processes through learning, adaptation, and evolutionary planning.

PMID- 21881439
TI  - Perspectives on executive relationships: influence.
AB  - This department, sponsored by AONE, presents information to assist nurse leaders
      in shaping the future of healthcare through creative and innovative leadership.
      The strategic priorities of AONE anchor the editorial content. They reflect
      contemporary healthcare and nursing practice issues that challenge nurse
      executives as they strive to meet the needs of patients. In this article, the
      author presents the views of 6 Magnet hospital chief nursing executives regarding
      their relationships with executive-level colleagues.

PMID- 21881438
TI  - County and state quality data to inform expanded roles for nursing's future.
AB  - In this department, Dr Newhouse highlights hot topics in nursing outcomes,
      research, and evidence-based practice relevant to the nurse administrator. The
      goal is to discuss the practical implications for nurse leaders in diverse
      healthcare settings. Content includes evidence-based projects and decision
      making, locating measurement tools for quality improvement and safety projects,
      using outcome measures to evaluate quality, practice implications of
      administrative research, and exemplars of projects that demonstrate innovative
      approaches to organizational problems. In this article, the author describes
      sources to identify major issues in healthcare quality, nursing's role in
      addressing quality issues, and Web-based resources for county and state quality
      data to guide nurses' future engagement.

PMID- 21881440
TI  - Adoption of national quality forum safe practices by Magnet(r) hospitals.
AB  - BACKGROUND: : Magnet hospitals (MHs) are known for their high retention rates of
      nurses and positive work environment, yet little is known about whether MHs also
      have higher levels of safe practice adoption rates compared with non-Magnet
      hospitals (NMHs). METHODS: : In this study, we investigate adoption of National
      Quality Forum (NQF) Safe Practices in 34 regions during 2004 to 2006 that were
      part of the Leapfrog Group initiative to improve quality of hospital care. We
      conducted a secondary data analysis by combining multiple data sets from the
      American Hospital Association Annual Survey, Healthcare Cost Reports Information
      System, and Leapfrog Group Annual Hospital Survey. A composite safe practice
      score (CSPS) was constructed from the Leapfrog annual survey and ranged from 0
      (no adoption) to 1,000 (complete adoption) of the 30 NQF Safe Practices. A
      descriptive analysis and a regression with Heckman correction to control for
      selection bias were used to determine the effect of Magnet status and other
      hospital and market characteristics on differences in CSPS over the 3-year
      period. RESULTS: : There were 140 MHs and 1,320 NMHs reporting data for the CSPS.
      In 2004, MHs had a mean CSPS of 865 versus 774 for NMHs (P < .001). By 2006, NMHs
      improved their CSPS from 774 to 872 (98 points), whereas MHs improved their CSPS
      from 865 to 925 (60 points, P < .001). Regression analysis showed a positive and
      significant effect of Magnet status of hospitals on the adoption rates of NQF
      Safe Practices as measured by the CSPS. Our results also indicated that smaller
      hospitals (in bed size), hospitals with larger share of Medicare patients, higher
      nurse intensity levels (mean hours of nursing care per day), and higher levels of
      competition among hospitals in Leapfrog rollout regions were associated with
      higher CSPS. CONCLUSION: : Magnet hospitals in the urban areas of 34 Leapfrog
      rollout regions were more likely to have higher adoption rates of NQF Safe
      Practices in comparison to NMHs in the same demographic areas during the time
      frame of the study, but other hospitals nearly closed the gap by 2006.

PMID- 21881441
TI  - Health information technology in the workplace: findings from a 2010 national
      survey of registered nurses.
AB  - The objective of this study was to examine RNs' experiences with health
      information technology (HIT) and their perceptions of the effect of this
      technology on quality of care and daily work. The adoption and use of HIT are
      expected to increase substantially over the next 5 years because of policy
      efforts at the federal and state levels. Given the size of the RN workforce and
      their critical role in healthcare delivery, their experiences with HIT could help
      adoption efforts. The method used was a nationally representative survey of 1500
      nurses with a 56% response rate. Findings suggest wide variation in the
      availability of HIT functionality, with functions more likely available to
      hospital RNs. Overall, RNs perceived the effect of these technologies on quality
      of care and their daily work as positive. Ensuring that HIT systems are relevant
      to and usable for RNs will be a critical component in achieving the meaningful
      use of these systems.

PMID- 21881442
TI  - Hands-free communication technology: a benefit for nursing?
AB  - The introduction of mobile communication devices (MCDs) has dramatically altered
      how nurses communicate. It is critical to assess whether these technologies
      contribute to stress and complicate the work of the nurse or if the devices are
      perceived as assisting in the provision of efficient and higher-quality patient
      care. The authors discuss a study that assessed the perceptions of nurses on a
      medical unit after MCDs were implemented.

PMID- 21881443
TI  - Visioning as a hiring strategy for quality outcomes.
AB  - Mutual trust and shared nurse leadership behaviors between the chief nurse
      executive and nursing staff are linked to improved clinical outcomes through an
      initial visioning process. The authors outline a hospital's strategy to improve
      nurse-driven outcomes by using visioning in the hiring process. Visioning,
      implemented in the hiring process, is a unique application of this tool for
      creating a desired future.

PMID- 21881444
TI  - Translating caring theory into practice: the Carolina Care Model.
AB  - This article describes how one organization operationalized Swanson Caring Theory
      and changed practice to ensure consistently high standards of performance. The
      Carolina Care Model developed at the University of North Carolina Hospitals is
      designed to actualize caring theory, support practices that promote patient
      satisfaction, and transform cultural norms. Evaluation suggests that this
      approach to care delivery enhances patients' and families' hospital experience
      and facilitates desired outcomes. The authors outline the Professional Practice
      Model, key characteristics of Carolina Care, links to caring theory, and
      development and implementation methodologies.

PMID- 21881445
TI  - A nurse practitioner residency pilot program: a journey of learning.
AB  - A collaborative team developed a year long residency experience for a staff nurse
      transitioning to a nurse practitioner role in the Veterans Affairs system. To
      assist others desiring to provide support, networking, and infrastructure to
      those transitioning into new roles, the authors discuss strengths and weaknesses
      of the pilot and lessons learned related to defining trainee versus resident,
      credentialing and privileging, and specific mentoring needed for the role of the
      nurse practitioner.

PMID- 21881446
TI  - 'Mild' nonobstructive coronary artery disease is often anything but.

PMID- 21881447
TI  - Prevalence, clinical characteristics and treatment patterns of low high-density
      lipoprotein cholesterol in the US population: National Health and Nutrition
      Examination Survey 2005-2008.
AB  - AIMS: The aims of this study were to estimate the prevalence of low high-density
      lipoprotein cholesterol (HDL-C) in US adults, assess the association between low
      HDL-C levels and clinical characteristics, and quantify the utilization of
      dyslipidemic agents as it relates to the distribution of HDL-C. METHODS: We
      analyzed a sample of 4129 adults (>20 years) who underwent fasting blood
      evaluations in the National Health and Nutrition Examination Survey (NHANES) 2005
      2008. Sex-specific crude and adjusted logistic models were developed to evaluate
      the association between individual characteristics and low HDL-C, in which low
      HDL-C was defined as less than 40  mg/dl for men and less than 50  mg/dl for
      women. RESULTS: Approximately 24% of men and 27% of women had low HDL-C levels.
      Factors most strongly associated with low HDL-C levels for men included being
      obese [odds ratio (OR) = 3.27, 95% confidence interval (CI): 1.98-5.40], having
      elevated triglyceride levels (>200  mg/dl: OR = 8.17, 95% CI: 5.54-12.03) and
      having apolipoprotein B levels more than 117  mg/dl (OR = 5.99, 95% CI: 2.74
      13.13). The same factors were associated with low HDL-C levels among women: being
      obese (OR = 2.89, 95% CI: 1.78-4.71), having elevated triglyceride levels (>200 
      mg/dl: OR = 13.35, 95% CI: 7.49-23.77) and having apolipoprotein B levels more
      than 117  mg/dl (OR = 5.88, 95% CI: 2.29-15.11). Approximately 82% of men and 79%
      of women with low HDL-C levels reported not using any dyslipidemic medication.
      CONCLUSION: Although having low HDL-C was common among US adults, few reported
      taking a dyslipidemic agent. Our study also confirmed some of the known risk
      factors associated with low HDL-C levels in the general US population.

PMID- 21881448
TI  - Giant left atrium syndrome.
AB  - Giant left atrium syndrome can occasionally occur in patients with rheumatic
      mitral valve regurgitation and can be responsible for oesophagus and/or airways
      compression. Abnormally enlarged left atriomegaly creates unusual right chest
      opacification on radiographs.

PMID- 21881450
TI  - Effects of add-on cilostazol on cognition in patients with schizophrenia: an open
      label pilot trial.

PMID- 21881451
TI  - Ibogaine-associated psychosis in schizophrenia: a case report.

PMID- 21881452
TI  - Haloperidol versus second-generation antipsychotics in the long-term treatment of
      schizophrenia: a 4-year follow-up naturalistic study.

PMID- 21881453
TI  - Antipsychotic drugs increase adipose stem cell differentiation--implications for
      treatment with antipsychotic drugs.

PMID- 21881454
TI  - Late-onset agranulocytosis in a patient treated with clozapine and lamotrigine.

PMID- 21881455
TI  - A self-limiting case of atypical neuroleptic malignant syndrome associated with
      zotepine.

PMID- 21881456
TI  - The effect of long-term use of risperidone on body weight of children with an
      autism spectrum disorder.

PMID- 21881457
TI  - A cytochrome P450 inhibitor in a stable schizophrenic patient: a drug
      interaction.

PMID- 21881458
TI  - Hyperosmolar hyperglycemic state associated with ziprasidone treatment: a case
      report.

PMID- 21881459
TI  - Memantine for comorbid obsessive-compulsive disorder and Asperger disorder
      suggests a link in glutamatergic dysregulation.

PMID- 21881460
TI  - Pregabalin augmentation in treatment-resistant obsessive-compulsive disorder: a
      16-week case series.

PMID- 21881461
TI  - Six-year mortality rates of patients in methadone and buprenorphine maintenance
      therapy: results from a nationally representative cohort study.

PMID- 21881462
TI  - Carnitine supplementation for valproate-related hyperammonemia to maintain
      therapeutic valproate level.

PMID- 21881463
TI  - Effects of baseline depression severity on remission rates with duloxetine and
      placebo in anxious and nonanxious patients with major depression.

PMID- 21881464
TI  - An update on brain death criteria: a simple algorithm with complex questions.
AB  - Brain death criteria have been based on 3 cardinal features throughout history:
      coma, brainstem areflexia, and apnea, and thus have undergone little change. In
      1995, the American Academy of Neurology (AAN) detailed these criteria in a step
      by-step fashion that included meeting prerequisites, performing the clinical
      examination, performing ancillary testing, and documentation. Fifteen years
      later, many questions still remain regarding the diagnosis of brain death. The
      Quality Standards Subcommittee of the AAN sought to answer 5 of these outstanding
      questions. Ultimately, their data supported the utility of the 1995 criteria and
      warned against the use of new technologies before proper validation. This review
      briefly tells the story of brain death criteria, making mention of the steps
      outlined by the AAN in 1995 and discussing the recent evidence released by the
      Quality Standards Subcommittee in the new 2010 Practice Parameter Update.

PMID- 21881465
TI  - Neurologic prognosis in cardiac arrest patients treated with therapeutic
      hypothermia.
AB  - BACKGROUND: Therapeutic hypothermia is now commonly used to improve neurologic
      outcomes in eligible patients after cardiac arrest. The physiologic effects of
      cooling and pharmacologic effects of sedatives and neuromuscular blocking agents
      can affect the clinical exam and neurophysiologic findings. This can lead to
      uncertainty in neurologic prognostication. In this article, we review data on
      assessing prognosis in patients treated with therapeutic hypothermia. REVIEW
      SUMMARY: Features of the clinical examination, neurophysiologic testing
      (including somatosensory-evoked potentials and electroencephalography),
      serum/cerebrospinal fluid biomarkers and neuroimaging can be used to help predict
      prognosis. However, no single test can predict poor prognosis with absolute
      certainty. Given the features that help to predict poor, indeterminate, or good
      outcome, we provide practical advice in assessing neurologic prognosis after
      cardiac arrest in patients treated with therapeutic hypothermia. CONCLUSIONS: The
      American Academy of Neurology practice parameters for assessing prognosis after
      cardiac arrest may not be accurate for patients treated with therapeutic
      hypothermia. Application of these guidelines may lead to overly pessimistic
      prognostication and premature withdrawal of care. If uncertainty exists regarding
      the prognosis in a given patient after cardiac arrest, additional time should be
      allowed to pass, as patients may ultimately recover with good neurologic outcome.

PMID- 21881466
TI  - Refractory epilepsy associated with microglial activation.
AB  - BACKGROUND: Experimental and clinical studies support a pathogenic role of
      microglial activation and proliferation (MAP) in epileptogenesis. METHODS: From a
      consecutive series of 319 surgically treated epilepsy cases, we retrospectively
      reviewed the histopathological sections of 92 cases to define the prevalence and
      severity of MAP after excluding the other 227 because of coexisting disorders
      that might contribute to MAP. Severity of MAP was compared with underlying
      abnormalities. We assessed the response to intravenous immunoglobulin and
      plasmapheresis in one patient with severe MAP who had failed multiple
      antiepileptic drugs and epilepsy surgery. RESULTS: MAP was detected with routine
      (hematoxylin and eosin) stain in 46 of 92 cases (50%). MAP was mild in 32 cases
      (69.6%), moderate in 12 (26.1%), and severe in 2 (4.3%). The prevalence and
      severity of MAP were independent of underlying abnormalities. Immunomodulatory
      therapy was followed by a greater than 90% reduction in seizure activity in the
      treated patient. CONCLUSION: MAP is prevalent in resected human epilepsy tissue.
      Failure to down-regulate MAP contributes to chronic neuronal hyperexcitability.
      We hypothesize that MAP initiates a cycle of inflammation-induced seizures and
      seizure-induced inflammation. Microglia-driven epilepsy may be a primary
      pathogenic process in a small number of cases, as suggested by the pathology and
      therapeutic response in our patient, but may contribute to epileptogenesis in
      many more.

PMID- 21881467
TI  - New insights in antiplatelet therapy for patients with ischemic stroke.
AB  - BACKGROUND: Acute treatment and long-term secondary prevention of
      noncardioembolic ischemic stroke and transient ischemic attack (TIA) include
      initiation of antiplatelet therapy. Antiplatelet agents currently used in the
      treatment of ischemic stroke and TIA are aspirin, clopidogrel, and dipyridamole.
      REVIEW SUMMARY: The safety and efficacy of antiplatelet therapy in patients with
      ischemic stroke, including a discussion of recent trial data and its influence on
      treatment guidelines, are presented. A brief discussion of the use of
      antiplatelet therapy in preventing stroke and embolism in patients with atrial
      fibrillation is also presented. For secondary prevention of ischemic events in
      patients with a history of stroke, clinical trials have shown the addition of
      dipyridamole to aspirin to be more effective than aspirin alone. The therapies
      are also similar from a standpoint of bleeding. The combination of aspirin and
      clopidogrel was not shown to be more efficacious and caused more bleeding than
      aspirin alone when evaluated for secondary prevention. However, dual antiplatelet
      therapy with aspirin and clopidogrel may have some benefit in the acute stroke
      setting or in the prevention of thrombotic events in patients with atrial
      fibrillation who cannot or will not take warfarin. CONCLUSIONS: Antiplatelet
      therapy is an important component of acute and long-term treatment of ischemic
      stroke and TIA. Ongoing clinical trials may help to refine what treatment
      regimens are best suited for acute and long-term therapy.

PMID- 21881468
TI  - DBS candidates that fall short on a levodopa challenge test: alternative and
      important indications.
AB  - INTRODUCTION: Candidacy for deep brain stimulation (DBS) in Parkinson disease
      (PD) is typically assessed by the preoperative motor response to levodopa along
      with an interdisciplinary evaluation. However, recent cases treated at our
      institution have achieved good outcomes with DBS despite a sub-30% improvement in
      motor scores. The aim of this study was to examine the outcomes of DBS in a
      subset of patients who failed to reach the 30% motor improvement threshold.
      METHODS: A review of all DBS patients treated at the University of Florida
      Movement Disorders Center between 2002 and 2009 was performed utilizing a DBS
      database. All patients with sub-30% improvement in Unified Parkinson Disease
      Rating Scale Part III after dopaminergic medication administration were included.
      RESULTS: Nine patients were identified; DBS was performed for severe dyskinesia
      (n=5), "on/off motor" fluctuations (n=1) and medication-refractory tremor (n=3).
      The target symptoms were improved in all patients. Postoperatively, scores on the
      Unified Parkinson Disease Rating Scale Part II and III and subscores on Parkinson
      disease questionnaire-39 improved (P<0.05). CONCLUSIONS: Although motor response
      to levodopa remains the primary selection criteria for DBS candidacy in Parkinson
      disease, patients who do not meet the 30% threshold and have disabling symptoms
      may still benefit from DBS. Select patients with severe dyskinesia, "on/off"
      motor fluctuations, and/or medication-refractory tremor may experience
      significant benefits from DBS and should be considered on a case by case basis
      through an interdisciplinary team evaluation.

PMID- 21881469
TI  - Gliomatosis cerebri diagnostic challenge: two case reports.
AB  - BACKGROUND: Gliomatosis cerebri is a specific entity defined as a diffuse
      neoplastic glial cell infiltration of the brain, preserving the architecture of
      the normal surrounding tissues, involving more than 2 cerebral lobes. Clinical
      symptoms or radiologic features are nonspecific, and patients are often
      misdiagnosed with other neurologic diseases. REVIEW SUMMARY: Here, we report the
      diagnostic workup of 2 patients with gliomatosis cerebri, discussing the
      clinical, radiologic, and pathologic findings. Case 1: a 64-year-old woman who
      presented with an intracranial hypertension syndrome and had symmetrical white
      matter T2-weighted and fluid-attenuated inversion recovery hyperintensities
      pattern on magnetic resonance imaging; and case 2: a 54-year-old man with the
      diagnosis of multiple sclerosis for 8 years who presented with de novo cognitive
      impairment and focal deficits. CONCLUSIONS: This report highlights the difficulty
      of this differential diagnosis and the need of considering it also in the
      presence of a symmetrical pattern of white matter involvement. Cerebral biopsy
      remains crucial for the correct diagnosis and treatment approach.

PMID- 21881470
TI  - Nonconvulsive status epilepticus related to posterior reversible
      leukoencephalopathy syndrome induced by cetuximab.
AB  - BACKGROUND: Reversible posterior leukoencephalopathy syndrome (PRES) is a
      relatively uniform clinical and neuroradiologic manifestation of central nervous
      system toxicity. The clinical features are headache, altered mental status, and
      visual disturbances. PRES is often associated with arterial hypertension but it
      is most usually related to drug toxicity. In fact, it has been related to
      immunosupressants, cytotoxic, and new antineoplastic-targeted therapies such as
      sorafenib, sunitinib, bevacizumab, bortezomib, rituximab, and etanercept. CASE
      REPORT: We describe a most unusual case of nonconvulsive status epilepticus
      related to PRES induced by cetuximab in a patient with metastatic squamous cell
      carcinoma of the penis. DISCUSSION: This case emphasizes that in any patient
      receiving treatment with anti-epidermal growth factor receptor agents and showing
      a compatible clinical syndrome, PRES should be suspected. We also review the
      clinical and neuroradiologic features of PRES, discuss its' pathogenesis, and
      highlight the importance of rapid recognition and withdrawal of the causative
      agent.

PMID- 21881471
TI  - Acute disseminated encephalomyelitis after mixed malaria infection (Plasmodium
      falciparum and Plasmodium vivax) with MRI closely simulating multiple sclerosis.
AB  - INTRODUCTION: Acute disseminated encephalomyelitis (ADEM) is a monophasic,
      inflammatory, immune-mediated disorder of the central nervous system. It is
      particularly difficult to distinguish between ADEM and an initial attack of
      multiple sclerosis (MS) clinically and based on magnetic resonance imaging (MRI)
      or cerebrospinal fluid. ADEM is quite rare after malaria infection. Our patient,
      although diagnosed provisionally of ADEM after mixed malaria infection, had
      neuroimaging closely simulating MS. CASE REPORT: We report a case of a woman with
      an adult type 2 diabetes presenting with fever and diagnosed by antigen assay to
      be suffering from mixed malaria infection (Plasmodium falciparum, Plasmodium
      vivax). While recovering with artesunate and doxycycline therapy, she developed
      acute onset bladder retention followed by paraparesis. On examination she had
      evidence of Upper Motor Neuron (UMN) signs in all the 4 limbs along with truncal
      sensory loss. DISCUSSION: Her MRI of spine showed T2 hyperintensities suggestive
      of resolving myelitis. MRI of the brain showed multifocal and confluent areas of
      demyelination mostly involving the corpus callosum and periventricular region.
      Lesions, particularly the callosal ones, closely simulated MS. In accordance with
      the McDonald Criteria and Barkhof's MRI Criteria, this patient did not fit into
      the diagnosis of MS. Our provisional diagnosis was ADEM.

PMID- 21881472
TI  - Lamotrigine withdrawal may worsen RBD symptoms.
AB  - BACKGROUND: Rapid eye movement (REM) behavior disorder (RBD) is a rapid eye
      movement parasomnia, which in its symptomatic type could be induced by the
      introduction or the discontinuation of several drugs and substances. No
      references for antiepileptic drugs and especially for lamotrigine are known
      regarding pharmacologically induced RBD. CASE REPORT: We report a case of a 68
      year-old man already suffering from RBD, who developed very brief episodes of
      epigastric discomfort followed by impaired consciousness and was given a
      diagnosis of epilepsy. Lamotrigine was started at 25 mg/d, reached a maximum of
      100 mg/d after 2 months and was retained at this dose for 1 more month. During
      this period there was a slight decrease in the episodes of impaired consciousness
      and no appreciable changes in the frequency and intensity of RBD symptomatology.
      Immediately following the abrupt discontinuation of lamotrigine, RBD
      symptomatology was severely aggravated, with dreams becoming more vivid and
      frightening and occurring almost every night. RBD symptomatology gradually
      subsided over 2 months, reaching levels comparable to those before lamotrigine.
      The impaired consciousness episodes remained unaffected and were considered to be
      nonepileptic. CONCLUSIONS: Our findings suggest that abrupt withdrawal of
      lamotrigine may worsen symptoms of comorbid idiopathic RBD.

PMID- 21881473
TI  - Unilateral GPi-DBS as a treatment for levodopa-induced respiratory dyskinesia in
      Parkinson disease.
AB  - BACKGROUND: Respiratory dyskinesia is a rare but disabling complication of
      levodopa therapy for Parkinson disease; however, its treatment has been limited
      to medication optimization. CASE REPORT: A 72-year-old woman with a 6-year
      history of Parkinson disease presented with severe and debilitating levodopa
      induced respiratory dyskinesia, which manifested with a short and shallow
      breathing pattern and panting. These symptoms were observed coincident with limb
      and truncal dyskinesias. Both respiratory and limb/trunk dyskinesias were
      addressed by the implantation of a unilateral globus pallidus interna deep brain
      stimulator (GPi-DBS). CONCLUSIONS: Although the mechanism of involvement of the
      respiratory system in dyskinesia is unknown, GPi-DBS seems to be a potentially
      viable treatment option for these patients.

PMID- 21881474
TI  - A coincidental case of young-onset Parkinson disease and multiple sclerosis.
AB  - BACKGROUND: Parkinsonism in patients with multiple sclerosis is rare. Some
      patients have 2 coincidental diseases, whereas others have a Parkinsonian
      syndrome symptomatic to demyelinating lesions. CASE REPORT: We describe a 42-year
      old female patient who developed left akinetic-rigid Parkinsonian syndrome at the
      age of 38 years. Brain magnetic resonance imaging revealed multiple white matter
      hyperintense T2-weighted lesions. DaTSCAN revealed reduced uptake of dopamine
      transporter in the right striatum. Intravenous corticosteroids were
      inefficacious. She had major clinical improvement with levodopa and 6 months
      later developed peak-dose dyskinesias. At the age of 41 years, she presented with
      a brainstem attack, with complete symptom resolution after intravenous
      corticosteroids. Subsequent brain magnetic resonance imagings disclosed new
      inflammatory lesions. Immunomodulatory treatment was started with beta
      interferon. COMMENTS: In this patient, the presence of an asymmetrical
      Parkinsonian syndrome, with good response to levodopa, peak-dose dyskinesias, and
      abnormal DaTSCAN, supports the diagnosis of young-onset Parkinson disease. The
      multiple sclerosis diagnosis was established based on clinical evidence of time
      and space dissemination of demyelinating lesions.

PMID- 21881475
TI  - Sleep apnea and white matter disease in hypertensive patients: a case series.
AB  - Obstructive sleep apnea (OSA) is associated with hypertension (HTN) and
      cardiovascular disease. Transient episodes of hypoxia, hypercapnia, and blood
      pressure elevation during OSA may lead to neural damage and subsequently white
      matter disease (WMD). As WMD is usually the result of chronic small vessel
      ischemia, a relationship between OSA and cerebrovascular disease may exist. This
      case series aimed to establish a relationship between OSA and WMD. Sixty-two
      patients without cerebrovascular disease who had both a polysomnogram and brain
      magnetic resonance imaging were identified. All patients carried the diagnosis of
      HTN. WMD was evaluated using the age-related white matter changes scale. Although
      half of the study population had WMD on magnetic resonance imaging, no
      association was found between WMD with severity of OSA (P=0.9). Our results are
      limited by the small sample size and by coexistent HTN in all patients. Further
      studies are needed to elucidate the relationship between OSA and WMD, especially
      among nonhypertensive patients. Future research should also address if OSA
      treatment has any effect on WMD.

PMID- 21881476
TI  - Intracerebral hemorrhage: an unusual presentation of neurosarcoidosis.
AB  - Neurosarcoidosis has a variety of clinical presentations. Common manifestations
      include leptomeningeal inflammation with seizures, headache, cranial nerve
      palsies, hydrocephalus, or focal neurological deficits with white matter lesions
      or mass lesions. Stroke is relatively rare, and hemorrhage is much less common
      than ischemia due to vasculitis. We present a patient with histopathologically
      confirmed neurosarcoidosis presenting with headache, seizures, and cognitive
      decline with multiple recurrent primary intracerebral hemorrhages.

PMID- 21881477
TI  - Risk of development of medication overuse headache with nonsteroidal anti
      inflammatory drug therapy for migraine: a critically appraised topic.
AB  - BACKGROUND: The development of medication overuse headache (MOH) is associated
      with frequent use of analgesics, especially opiates, for treatment of primary
      headache disorders, particularly migraine. Nonsteroidal anti-inflammatory drugs
      (NSAIDs) are commonly used to treat migraine. OBJECTIVE: To critically evaluate
      evidence estimating the risk of MOH associated with NSAID therapy in patients
      with migraine. METHODS: The objective was addressed through the development of a
      structured, critically appraised topic. This included a clinical scenario,
      structured question, literature search strategy, critical appraisal, results,
      evidence summary, commentary, and bottom line conclusions. Participants included
      consultant and resident neurologists, a medical librarian, clinical
      epidemiologists, and headache neurology content experts. RESULTS: The 1-year
      incidence of MOH was 2.5%. In patients with low (0 to 4 d monthly) to moderate (5
      to 9 d monthly) baseline headache frequency, NSAIDs were not associated with
      progression to MOH and may be protective (odds ratio=0.31; 95% confidence
      interval, 0.27-0.34). However, in patients with a high baseline headache
      frequency (10 to 14 d monthly), NSAIDs are associated with progression to MOH
      (odds ratio=1.93; 95% confidence interval, 1.82-2.06). CONCLUSIONS: Acute NSAID
      therapy is associated with progression to MOH in migraineurs with a high baseline
      migraine frequency but may be protective in patients with low baseline headache
      frequency. However, a causal role for NSAIDs in progression from episodic to
      chronic headache has not been established.

PMID- 21881478
TI  - Phase 2 double-blind, randomized trial of etravirine versus efavirenz in
      treatment-naive patients:  48-week results.
AB  - BACKGROUND: The Study of Etravirine Neuropsychiatric Symptoms versus Efavirenz
      (SENSE) trial compared etravirine with efavirenz in treatment-naive patients. The
      primary endpoint was neuropsychiatric adverse events up to week 12; HIV RNA
      suppression at week 48 was a secondary endpoint. METHODS: Patients with HIV RNA
      more than 5000  copies/ml were randomized to etravirine 400  mg once daily (n =
      79) or efavirenz (n = 78), plus two nucleoside analogues. HIV RNA less than 50 
      copies/ml at week 48 was analysed using the time to loss of virological response
      (TLOVR) algorithm. Drug resistance at treatment failure and safety endpoints were
      also evaluated. RESULTS: At baseline, the median CD4 cell count was 302 
      cells/MUl and HIV RNA was 4.8 log10  copies/ml. In the intent to treat TLOVR
      analysis at week 48, 60 of 79 (76%) patients on etravirine versus 58 of 78 (74%)
      on efavirenz had HIV RNA less than 50  copies/ml. In the on-treatment analysis,
      60 of 65 (92%) taking etravirine had HIV RNA les than 50 copies/ml versus 58 of
      65 (89%) for efavirenz: etravirine showed noninferior efficacy versus efavirenz
      in both analyses (P < 0.05). Four patients had virological failure in the
      etravirine arm: none developed resistance to nucleoside analogues or
      nonnucleosides. Seven patients had virological failure in the efavirenz arm:
      three developed treatment-emergent resistance to nucleoside analogues and/or
      nonnucleosides. At the week 48 visit, the percentage with ongoing
      neuropsychiatric adverse events was 6.3% for etravirine and 21.5% for efavirenz
      (P = 0.011). CONCLUSION: First-line treatment with etravirine 400 mg once daily
      and two nucleoside reverse transcriptase inhibitors (NRTIs) led to similar rates
      of HIV RNA suppression, compared with efavirenz and two NRTIs. None of the
      patients with virological failure in the etravirine arm developed resistance to
      nonnucleosides.

PMID- 21881479
TI  - HIV seroprevalence among orphaned and homeless youth:  no place like home.
AB  - OBJECTIVES: We evaluated the combined influences of orphaned status and
      homelessness on HIV seroprevalence and risk among street-involved Ukrainian youth
      in 2008. DESIGN: Systematic, multicity, community-based, cross-sectional
      assessment. METHODS: Time-location sampling was used to identify eligible youth
      aged 15-24 after city-wide mapping of 91 sites where street-involved youth
      gathered in Odessa, Kiev, and Donetsk. Universal sampling identified 961 youth in
      74 randomly selected sites; 97% consented. Youth reporting one or both parents
      dead were classified as orphaned; those without a stable residence or sleeping
      outside their residence at least two nights per week were classified as homeless.
      Trained staff provided HIV counseling and rapid testing via mobile vans. Adjusted
      odds ratios (AORs) were calculated using logistic regression, accounting for
      intracluster homogeneity. RESULTS: We found 32% (300 of 929) were both orphaned
      and homeless; 48% either (but not both) homeless [37% (343 of 929)] or orphaned
      [11% (104 of 929)]; and [20% (182 of 929)] neither orphaned nor homeless. HIV
      seroprevalences were 7% for neither orphaned/homeless; 16 and 17%, respectively,
      for either orphaned/homeless; 28% for both orphaned/homeless (P for trend
      <0.0001). AORs for HIV infection were 1 for neither; 2.3 and 2.4 for either
      homeless [95% confidence interval (CI) 1.7-2.9] or orphaned (CI 1.8-3.3); 3.3 for
      both orphaned/homeless (CI 2.3-4.4). Ever-use of injection drugs increased from
      15 to 32 to 48% for those who neither, either, or both orphaned and homeless,
      respectively (P for trend <0.0001). CONCLUSIONS: One of four youths who were both
      homeless and orphaned was HIV-infected; these youths were significantly more
      likely to be HIV infected and to report injection drug use than those with
      adequate housing and living parents.

PMID- 21881480
TI  - Mortality and immunovirological outcomes on antiretroviral therapy in HIV-1 and
      HIV-2-infected individuals in the Gambia.
AB  - OBJECTIVES: This study's objective was to assess outcomes in HIV-1 and HIV-2
      infected antiretroviral therapy (ART)-naive patients starting ART in the Gambia,
      West Africa. DESIGN: A cohort design was used to estimate survival in ART
      patients and determine whether survival and time to virologic failure varied
      across patient subgroups. METHODS: Mortality, virologic failures and CD4(+) cell
      recovery were assessed in a clinical cohort of patients from the Genito-Urinary
      Medicine (GUM) clinic of the MRC Laboratories in the Gambia. Kaplan-Meier
      estimates of survival were determined for mortality and virologic failure. A Cox
      proportional hazards model was used to identify baseline demographic, clinical,
      immunologic and virologic factors associated with increased risk of death.
      RESULTS: The overall Kaplan-Meier estimate of survival to 36 months was 73.4%
      (66.5, 80.3). Survival was marginally higher in HIV-2-infected patients compared
      to HIV-1-infected patients; it was significantly higher in patients with a
      baseline CD4(+) lymphocyte cell count of greater than 50 cells/MUl compared to
      those with a baseline CD4(+) count of less than 50 cells/MUl. CD4(+) cell
      recovery was faster in HIV-1-infected individuals compared to HIV-2-infected
      patients up to 24 months, although this did not result higher mortality in the
      latter group. No differences in virologic failure were observed by HIV type.
      CONCLUSION: HIV-1 and HIV-2-infected patients receiving ART in a clinical setting
      in the Gambia had good survival to 36 months. HIV-2-infected patients did as well
      as HIV-1-infected patients in terms of long-term immunological and virological
      responses and overall survival.

PMID- 21881481
TI  - Impact of CD8+ T-cell activation on CD4+ T-cell recovery and mortality in HIV
      infected Ugandans initiating antiretroviral therapy.
AB  - OBJECTIVES: To assess whether T-cell activation independently predicts the extent
      of CD4(+) T-cell recovery and mortality in HIV-infected Ugandans initiating
      antiretroviral therapy (ART). DESIGN: Prospective cohort study. METHODS: HIV
      infected adults starting ART and achieving a plasma HIV RNA level (VL) less than
      400 copies/ml by month 6 were sampled from the Uganda AIDS Rural Treatment
      Outcomes (UARTO) cohort in Mbarara, Uganda. CD4 count, VL, and the percentage
      activated (CD38(+)HLA-DR(+)) T cells were measured every 3 months. RESULTS: Of
      451 HIV-infected Ugandans starting ART, most were women (70%) with median pre-ART
      values: age, 34 years; CD4 count, 135 cells/MUl; and VL, 5.1 log(10) copies/ml.
      Of these, 93% achieved a VL less than 400 copies/ml by month 6 and were followed
      for a median of 24 months, with 8% lost to follow-up at 3 years. Higher pre-ART
      CD8(+) T-cell activation was associated with diminished CD4 recovery after year
      1, after adjustment for pre-ART CD4 count, VL, and sex (P = 0.017). Thirty-four
      participants died, 15 after month 6. Each 10% point increase in activated CD8(+)
      T cells at month 6 of suppressive ART was associated with a 1.6-fold increased
      hazard of subsequent death after adjusting for pretherapy CD4 count (P = 0.048).
      CONCLUSIONS: Higher pre-ART CD8(+) T-cell activation independently predicts
      slower CD4(+) T-cell recovery and higher persistent CD8(+) T-cell activation
      during ART-mediated viral suppression independently predicts increased mortality
      among HIV-infected Ugandans. Novel therapeutic strategies aimed at preventing or
      reversing immune activation during ART are needed in this setting.

PMID- 21881482
TI  - Neurological manifestations of coinfection with HIV and human T-lymphotropic
      virus type 1.
AB  - HIV-individuals are at risk for human T-lymphotropic virus (HTLV) coinfection and
      neurological diseases. Little is known about the impact of HAART among coinfected
      patients. In this study, 47 out of 428 HIV individuals were coinfected with HTLV
      (10.9%). Coinfection was an independent variable associated with neurological
      outcome (odds ratio 8.73). Coinfection was associated with myelopathy [chi square
      (X(2)) = 93, P < 0.001], peripheral neuropathy (X(2) = 6.5, P = 0.01), and
      hepatitis C virus infection (X(2) = 36.5, P < 0.001). HAART did not appear to
      protect against neurological diseases and had no impact on HTLV proviral load.

PMID- 21881483
TI  - Clinical relevance of detection of lymphovascular invasion in primary melanoma
      using endothelial markers D2-40 and CD34.
AB  - Immunohistochemistry (IHC) using endothelial markers may facilitate the detection
      of lymphovascular invasion (LVI) in primary melanoma; however, the clinical
      implications of enhanced detection are unknown. We evaluated whether the use of
      lymphatic endothelial marker D2-40 and panvascular marker CD34 increases LVI
      positivity relative to routine histology alone and then evaluated the prognostic
      relevance of LVI detected using these markers in terms of disease-free (DFS) and
      overall survival (OS). A total of 246 primary melanomas were assessed for LVI
      using D2-40, CD34, and routine histology. Associations between LVI positivity and
      clinicopathologic variables, DFS, and OS were compared using univariate and
      multivariate analyses. The use of endothelial markers increased the rate of LVI
      positivity (18% using D2-40 and/or CD34 vs. 3% by routine histology, P<0.0001).
      On univariate analysis, IHC-detected LVI was significantly associated with more
      adverse clinicopathologic variables (thickness, ulceration, mitoses, and nodular
      subtype) compared with LVI detected by routine histology (thickness and
      ulceration only). In a multivariate model controlling for stage, LVI detected
      using IHC markers remained a significant marker of both reduced DFS [hazard ratio
      (HR), 2.01; 95% confidence interval (CI): 1.27-3.18; P=0.003] and OS (HR, 2.08;
      95% CI: 1.25-3.46; P=0.005). Results show that D2-40 and CD34 increase the
      detection of LVI in primary melanoma and that cases missed by routine histology
      have prognostic relevance.

PMID- 21881484
TI  - Important histologic outcome predictors for patients with invasive ductal
      carcinoma of the breast.
AB  - The pathologic diagnosis is regarded as the final diagnosis of a disease, and
      pathologic examination based on tumor histology is very important for the
      accurate assessment of the biological characteristics of tumors. The purpose of
      this study was to investigate the histologic factors that accurately predict
      patient outcome among 1042 patients with invasive ductal carcinoma of the breast.
      Both well-known histologic factors and our proposed histologic factors were
      examined according to several tumor statuses using multivariate analysis. This
      study clearly demonstrated that type 4 invasive ductal carcinomas having fibrotic
      foci and atypical tumor-stromal fibroblasts within the fibrotic foci are
      significant outcome predictors for lymph node-negative and lymph node-positive,
      the pathologic UICC-TNM stage II and III, luminal A-subtype, luminal B-subtype,
      and equivocal HER2 subtype invasive ductal carcinoma patients. Lymph vessel tumor
      embolus grades 2 and 3 were significant outcome predictors for lymph node
      positive, UICC pTNM stages II and III, luminal A-subtype, and triple-negative
      invasive ductal carcinoma patients (except lymph vessel tumor embolus grade 2 in
      luminal A-subtype patients). More than 5 mitotic figures in metastatic carcinoma
      to the lymph nodes was a significant outcome predictor for lymph node-positive,
      UICC pTNM stage II, and luminal A-subtype invasive ductal carcinoma patients. A
      fibrotic focus diameter >8 mm was a significant outcome predictor for UICC pTNM
      stages I and III invasive ductal carcinoma patients. These findings strongly
      suggest that these histologic factors are very useful for accurately predicting
      the outcomes of patients with invasive ductal carcinoma of the breast.

PMID- 21881485
TI  - Diandric triploid hydatidiform mole with loss of maternal chromosome 11.
AB  - Distinction of hydatidiform moles (HM) from nonmolar specimens and their
      subclassification as complete (CHM) versus partial hydatidiform mole (PHM) are
      important for clinical practice and investigational studies to refine
      ascertainment of risk of persistent gestational trophoblastic disease (GTD),
      which differs among these entities. Immunohistochemical analysis of p57
      expression, a paternally imprinted maternally expressed gene on 11p15.5, and
      molecular genotyping are useful for improving diagnosis. CHMs are characterized
      by androgenetic diploidy, with loss of p57 expression due to lack of maternal
      DNA. Loss of p57 expression distinguishes CHMs from both PHMs (diandric
      triploidy) and nonmolar specimens (biparental diploidy), which retain expression.
      We report a unique HM characterized by morphologic features suggesting an early
      CHM, including lack of p57 expression by immunohistochemistry, but with genetic
      features more in keeping with a PHM. Specifically, molecular genotyping by short
      tandem repeat markers provided evidence to support interpretation as a PHM by
      demonstrating allele patterns and ratios most consistent with diandric triploidy,
      with evidence of loss of the maternal copy of chromosome 11 to explain the lack
      of p57 expression. This case illustrates the value of combined traditional
      pathologic and ancillary molecular techniques for refined diagnosis of molar
      specimens. It also raises questions regarding which modalities should be used to
      ultimately define the subtypes of HMs and whether chromosomal losses or gains,
      particularly involving imprinted genes such as p57, might play a role in
      modifying risk of persistent GTD.

PMID- 21881487
TI  - Combined melanocytic nevi: histologic variants and melanoma mimics.
AB  - Combined melanocytic nevi are composed of 2 or more distinct populations of
      nevomelanocytes. Most commonly used to describe the combination of blue nevi with
      common nevi, it may also be applied to other combinations of benign melanocytic
      proliferations, including Spitz nevi and nevi with deep dermal pigmented
      nevomelanocytes. We report the incidence and distribution of these tumors at the
      Massachusetts General Hospital over the past decade and review guidelines for
      diagnostic criteria and nomenclature. Between 2000 and 2010 we identified 511
      cases of combined nevi, represented by 4 histologically distinct diagnostic
      categories: (1) blue nevus, (2) nevi with deep dermal pigmented nevomelanocytes
      (plexiform/deep penetrating, inverted type A/clonal), (3) Spitz or pigmented
      spindled cell nevus, combined with another type of nevus (usually common or
      dysplastic), and (4) other combinations including 2 or more nevus types. Nearly
      one fifth of these tumors displayed atypical features; atypia was observed more
      often in combined nevi with Spitz or deep pigmented elements (26 of 55, 47%, and
      25 of 98, 26%, respectively) than in combined common and blue nevi (37 of 336,
      11%). Clinical follow-up data were available for 83% of the patients with
      atypical combined nevi; none developed recurrence or metastasis with a mean
      follow-up of over 4 years.

PMID- 21881486
TI  - Immunoexpression status and prognostic value of mTOR and hypoxia-induced pathway
      members in primary and metastatic clear cell renal cell carcinomas.
AB  - The need for effective targeted therapies for renal cell carcinomas (RCCs) has
      fueled the interest for understanding molecular pathways involved in the
      oncogenesis of kidney tumors. Aiming to analyze the expression status and
      prognostic significance of mTOR and hypoxia-induced pathway members in patients
      with clear cell RCC (ccRCC), tissue microarrays were constructed from 135 primary
      and 41 metastatic ccRCCs. Immunoexpression levels were compared and correlated
      with clinicopathologic parameters and outcome. PTEN levels were significantly
      lower in primary and metastatic ccRCCs compared with benign tissues (P<0.001).
      Levels of phos-AKT, phos-S6, and 4E-binding protein-1 (4EBP1) were higher in
      metastatic ccRCC (P<=0.001). For phos-S6 and 4EBP1, levels were higher in primary
      ccRCC compared with benign tissues (P<0.001). c-MYC levels were higher in
      metastatic ccRCC (P<0.0001), and incremental p27 levels were observed in benign,
      primary ccRCC, and metastatic ccRCC (P<0.0001). HIF-1alpha levels were
      significantly higher in primary and metastatic ccRCCs compared with benign
      tissues (P<0.0001). In primary ccRCC, levels of all mTOR and hypoxia-induced
      pathway members were significantly associated with pT stage (P<=0.036), p27
      levels with Fuhrman grade (P=0.031), and 4EBP1, p27, and HIF-1alpha levels with
      tumor size (P<=0.025). Tumor size, HIF-1alpha, and phos-S6 levels were associated
      with disease-specific survival (DSS) (P<=0.032) and tumor progression (P<=0.043).
      In conclusion, both mTOR and hypoxia-induced pathways were activated in primary
      and metastatic ccRCC. PTEN loss seems to be an early event during tumorigenesis.
      Tumor size, HIF-1alpha, and phos-S6 expression were found to be independent
      predictors of both DSS and tumor progression in primary ccRCC.

PMID- 21881488
TI  - beta-catenin (CTNNB1) S33C mutation in ovarian microcystic stromal tumors.
AB  - Microcystic stromal tumor (MCST) is a recently described subtype of ovarian tumor
      characterized by prominent microcystic histologic pattern and diffuse
      immunoreactivity for CD10 and vimentin. However, its pathobiology, particularly
      its histogenesis, remains largely unclear. Here, we report 2 cases of ovarian
      MCST, in which we have performed extensive histologic, immunohistochemical, and
      genetic investigations to determine its distinct nature among ovarian neoplasms.
      The patients were 32 and 41 years of age. Both tumors were solid and cystic
      masses involving the right ovary. Microscopically, tumor cells with generally
      bland, round-to-ovoid nuclei grew in microcystic, macrocystic, and solid
      patterns. Intervening thick fibrous stroma was observed. Immunohistochemically,
      tumor cells were diffusely and strongly positive for CD10, vimentin, and Wilms
      tumor 1. Furthermore, we detected aberrant nuclear expression of beta-catenin
      protein in both cases. Of interest, mutation analyses revealed the presence of an
      identical point mutation, c.98C>G, in exon 3 of beta-catenin (CTNNB1) in both
      tumors. This is an oncogenic mutation that causes replacement of serine with
      cysteine at codon 33, leading to the loss of a phosphorylation site in the beta
      catenin protein. The results of this study strongly suggest that dysregulation of
      the Wnt/beta-catenin pathway plays a fundamental role in the pathogenesis of
      ovarian MCST. Finally, by comparing the immunophenotype of MCST with its
      histologic mimics and other ovarian sex cord-stromal tumors, we were able to
      identify unique features of MCST and a panel of markers useful in differential
      diagnosis.

PMID- 21881489
TI  - Determining the site of origin of mucinous adenocarcinoma:  an
      immunohistochemical study of 175 cases.
AB  - Mucinous adenocarcinomas (MAs) of various origins may have a similar histologic
      appearance and frequently metastasize to distant sites, which often causes
      diagnostic problems in surgical pathology practice. The immunohistochemical
      profiles of MAs of various origins have not been well studied. We investigated
      the expression of 10 immunohistochemical markers (CK7, CK20, CDX-2, beta-catenin,
      MUC-1, MUC-2, MUC-6, ER, WT-1, and PAX-8) in 175 cases of MA, including 69 cases
      from the lower gastrointestinal (GI) tract, 41 from the upper GI tract, 27 from
      gynecologic organs, 4 from the urinary bladder, 18 from the breast, and 16 from
      the lung. We found that lower GI MAs (colon, rectum, and anus) frequently
      expressed CDX-2 (42 of 42, 100%; 33 of 42 with homogenous positivity, 79%), MUC-2
      (42 of 42; 100%), CK20 (41 of 42; 98%), and beta-catenin (nuclear) (27 of 42;
      64%) and rarely expressed MUC-6 (2 of 42; 5%) and CK7 (8 of 42; 19%). Most of the
      CK7-positive cases were from the rectum and anus (7 of 8; 88%). The expression of
      these markers in appendiceal MAs was similar to that of low GI tract MAs, except
      for a lower percentage of homogenous CDX-2 (3 of 27; 11%) and nuclear beta
      catenin (3 of 27; 11%) expression. Unlike their lower GI tract counterparts, the
      upper GI tract MAs (ampulla, pancreas/biliary tree, and stomach/esophagus)
      frequently expressed CK7 (38 of 41; 93%) and MUC-6 (31 of 41; 76%) and were
      rarely homogenously positive for CDX-2 (4 of 41; 10%) and nuclear positive for
      beta-catenin (8 of 41; 19%). Breast MAs were frequently positive for CK7 (18 of
      18; 100%), MUC-1 (18 of 18; 100%), MUC-2 (18 of 18; 100%), ER (16 of 18; 89%),
      MUC-6 (9 of 18; 50%), and WT-1 (9 of 18; 50%). Lung MAs were frequently positive
      for CK7 (16 of 16; 100%) and MUC-1 (15 of 16; 94%). Gynecologic MAs were positive
      for CK7 (25 of 27; 93%) and PAX-8 (13 of 27; 48%). We conclude that homogenous
      CDX-2 and nuclear beta-catenin expressions are commonly seen in lower GI tract
      MAs. In contrast, appendiceal MAs are usually heterogenously positive for CDX-2
      and show cytoplasmic positivity for beta-catenin. Unlike lower GI tract MAs,
      upper GI tract MAs are frequently positive for CK7 and MUC-6. As is the case in
      appendiceal MAs, the upper GI tract MAs may also be heterogenously positive for
      CDX-2. Breast MAs are positive for ER and WT-1, whereas gynecologic MAs are
      positive for PAX-8 and negative for WT-1.

PMID- 21881490
TI  - Posterior reversible encephalopathy syndrome as a cause of postoperative
      blindness.

PMID- 21881491
TI  - Structural studies of the actions of anesthetic drugs on the gamma-aminobutyric
      acid type A receptor.
AB  - The gamma-aminobutyric acid type A receptor is the major transmitter-gated
      inhibitory channel in the central nervous system. The receptor is a target for
      anesthetics, anticonvulsants, anxiolytics, and sedatives whose actions facilitate
      the flow of chloride ions through the channel and enhance the inhibitory tone in
      the brain. Both the kinetic and structural aspects of the actions of modulators
      of the gamma-aminobutyric acid type A receptor are of great importance to
      understanding the molecular mechanisms of general anesthesia. In this review, the
      structural rearrangements that take place in the gamma-aminobutyric acid type A
      receptor during channel activation and modulation are described, focusing on data
      obtained using voltage-clamp fluorometry. Voltage-clamp fluorometry entails the
      binding of an environmentally sensitive fluorophore molecule to a site of
      interest in the receptor, and measurement of changes in the fluorescence signal
      resulting from activation- or modulation-elicited structural changes. Detailed
      investigations can provide a map of structural changes that underlie or accompany
      the functional effects of modulators.

PMID- 21881492
TI  - Gestational gigantomastia and anesthesia.

PMID- 21881493
TI  - Laparoscopic versus open anterior abdominal wall hernia repair: 30-day morbidity
      and mortality using the ACS-NSQIP database.
AB  - OBJECTIVE: To compare short-term outcomes after laparoscopic and open abdominal
      wall hernia repair. METHODS: Using the American College of Surgeons National
      Surgical Quality Improvement Program (ACS-NSQIP) database (2005-2009), 71,054
      patients who underwent an abdominal wall hernia repair were identified (17%
      laparoscopic, 83% open). Laparoscopic and open techniques were compared.
      Regression models and nonparametric 1:1 matching algorithms were used to minimize
      the influence of treatment selection bias. The association between surgical
      approach and risk-adjusted adverse event rates after abdominal wall hernia repair
      was determined. Subgroup analysis was performed between inpatient/outpatient
      surgery, strangulated/reducible, and initial/recurrent hernias as well as between
      umbilical, incisional and other ventral hernias. RESULTS: Patients undergoing
      laparoscopic repair were less likely to experience an overall morbidity (6.0% vs.
      3.8%; odds ratio [OR], 0.62; 95% confidence interval [CI], 0.56-0.68) or a
      serious morbidity (2.5% vs. 1.6%; OR, 0.61; 95% CI, 0.52-0.71) compared to open
      repair. Analysis using multivariate adjustment and patient matching showed
      similar findings. Mortality rates were the same. Laparoscopically repaired
      strangulated and recurrent hernias, had a significantly lower overall morbidity
      (4.7% vs. 8.1%, P < 0.0001 and 4.1% vs. 12.2%, P < 0.0001, respectively).
      Significantly lower overall morbidity was also noted for the laparoscopic
      approach when the hernias were categorized into umbilical (1.9% vs. 3.0%, P =
      0.009), ventral (3.9% vs. 6.3%, P < 0.0001), and incisional (4.3% vs. 9.1%, P <
      0.0001). No differences were noted between laparoscopic and open repairs in
      patients undergoing outpatient surgery, when the hernias were reducible.
      CONCLUSION: Laparoscopic hernia repair is infrequently used and associated with
      lower 30-day morbidity, particularly when hernias are complicated.

PMID- 21881494
TI  - Management of anterior cutaneous nerve entrapment syndrome in a cohort of 139
      patients.
AB  - OBJECTIVE: Anterior cutaneous nerve entrapment syndrome (ACNES) is generally
      neglected as a source of chronic abdominal pain. The aim of this study was to
      evaluate the efficacy of a diagnostic workup protocol and treatment regimen in
      patients with suspected ACNES. METHODS: A cohort of all consecutive patients
      presenting with chronic abdominal pain suggestive of ACNES between 2003 and 2008
      was evaluated retrospectively. Patients were offered a single diagnostic
      injection of 1% lidocaine into the trigger point followed by subsequent
      therapeutic injections including corticosteroids. If pain was refractory, an
      anterior neurectomy was performed. Pain scores were done using a visual analog
      scale for evaluation of the injection regimen and Verbal Rating Scale (1-5) for
      long-term efficacy. RESULTS: A total of 139 patients with suspected ACNES (77%
      women, mean age 47 +/- 17 years) were evaluated. Eighty-one percent (n = 94)
      demonstrated a visual analog scale reduction of at least 50% after the first
      injection. Some 33% (n = 44) remained permanently pain-free after injection
      therapy only. Sixty-nine patients underwent a neurectomy, which was successful in
      49 (71%). Long-term efficacy revealed in 71% (very) satisfying visual rating
      scale (1-2) results, whereas an additional 9% reported attenuated levels of pain
      (visual rating scale 3). CONCLUSION: A regimen of consecutive local trigger point
      injections is effective in one-thirds of patients with ACNES. Surgical neurectomy
      is effective in about two-thirds of the injection regimen refractory patients.
      Eighty percent of the entire ACNES population reports total or substantial pain
      relief on the long term.

PMID- 21881495
TI  - Safety and efficacy of long-term disulfiram aftercare.
AB  - OBJECTIVES: Disulfiram is effective in relapse prevention in alcoholism. However,
      the optimal therapeutic aftercare regimen for patients is still unclear, and
      disulfiram is associated with numerous adverse events. Also, it is not clear if
      supervised long-term disulfiram treatment is safe and sufficiently efficient in
      the long run. METHODS: We evaluated the clinical outcome data of 10 alcohol
      dependent patients who underwent supervised treatment with disulfiram for more
      than 50 weeks. RESULTS: Seven of 10 patients remained completely abstinent during
      the supervised disulfiram therapy for a mean (SD) period of 70.1 +/- 23.5 months.
      For the 3 patients with relapse, the first relapse occurred after a mean (SD) of
      34.7 +/- 15.5 months. Liver enzymes in the blood decreased markedly under
      treatment with disulfiram. The overall tolerability was considered to be high;
      only dizziness and fatigue were observed in 4 patients in the initial phase of
      the therapy. No serious adverse events were recorded. CONCLUSIONS: Although case
      observations should be interpreted with caution, the present results suggest that
      disulfiram is safe and efficient in supervised long-term treatment of alcohol
      dependent patients.

PMID- 21881496
TI  - Deep anterior lamellar keratoplasty for corneal opacification in Maroteaux-Lamy
      syndrome: is it the treatment of choice?

PMID- 21881497
TI  - Multiple roles of angiopoietins in atherogenesis.
AB  - PURPOSE OF REVIEW: The roles of angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2)
      during vascular development have been extensively investigated, as has been their
      role in controlling the responsiveness of the endothelium to exogenous cytokines.
      However, very little is known about the role of these vascular morphogenic
      molecules in the pathogenesis of atherosclerosis. Here, we summarize the recent
      research into angiopoietins in atherosclerosis. RECENT FINDINGS: Angiopoietin-2
      is a context-dependent agonist that protects against the development of
      arteriosclerosis in rat cardiac allograft. A recent study showed, contrary to
      expectations, that a single systemic administration of adenoviral Ang-2 to apoE
      mice, fed a Western diet, reduced atherosclerotic lesion size and LDL oxidation
      in a nitric oxide synthase dependent manner. In contrast, overexpression of Ang-1
      fails to protect from rat cardiac allograft due to smooth muscle cell activation.
      The potential proatherogenic effect of Ang-1 is further supported by the
      induction of chemotaxis of monocytes by Ang-1 in a manner that is independent of
      Tie-2 and integrin binding. These studies highlight the need for extensive
      research to better understand the role of angiopoietins in the cardiovascular
      setting. SUMMARY: Ang-2 inhibits atherosclerosis by limiting LDL oxidation via
      stimulation of nitric oxide production. In contrast, Ang-1 can promote monocyte
      and neutrophil migration. The angiopoietin-Tie-2 system provides an important new
      target for modulating vascular function.

PMID- 21881498
TI  - Current understanding of the role of B cell subsets and intimal and adventitial B
      cells in atherosclerosis.
AB  - PURPOSE OF REVIEW: Inflammation, in addition to high cholesterol is a major
      factor contributing to atherosclerosis-associated adverse cardiovascular events.
      Thus, there is a pressing need for additional therapeutic strategies to reduce
      inflammation, by targeting immune cells and cytokines. Here we review B cell
      subsets and adventitial and intimal B cells in atherosclerosis development and
      discuss potential B cell-targeted anti-inflammatory therapies for
      atherosclerosis. RECENT FINDINGS: B cell subsets can have opposing proatherogenic
      and atheroprotective roles in atherosclerosis. CD-20-targeted B cell depletion
      has been shown to decrease murine atherosclerotic lesions. The accumulation of
      intimal and adventitial B cells associated with atherosclerotic lesions is
      consistent with their participation in local inflammatory responses. As B2 B
      cells are proatherogenic, blocking its survival factor B cell activating factor
      may selectively delete this proatherogenic subset. SUMMARY: Both intimal and
      adventitial B cells appear important in atherosclerosis. B2 B cells are
      proatherogenic and other subsets such as regulatory B cells are antiatherogenic.
      Future B cell-targeted therapy for atherosclerosis should be customized to
      selectively deplete damaging B2 B cells while sparing or expanding protective B
      cell subsets.

PMID- 21881500
TI  - HDLs, immunity, and atherosclerosis.
AB  - PURPOSE OF REVIEW: HDLs possess several physiological activities that may explain
      their antiatherosclerotic properties. Among them, the most relevant is the
      ability of HDL to promote the efflux of excess cholesterol from peripheral
      tissues to the liver for excretion. RECENT FINDINGS: The ability of HDL to
      promote cholesterol efflux results also in the modulation of a series of
      responses in the immune cells involved in atherosclerosis, including monocyte
      macrophages, B and T lymphocytes. HDL also acts as a reservoir for a number of
      biologically active substances that may impact the immune system, and as the HDL
      composition varies to a large extent during inflammation. SUMMARY: The
      understanding of how these interactions take place and how biologically active
      substances can be delivered to relevant targets during atherogenesis is of great
      interest and may provide a better understanding for the role of HDL in
      atherogenesis.

PMID- 21881499
TI  - Receptor-independent fluid-phase pinocytosis mechanisms for induction of foam
      cell formation with native low-density lipoprotein particles.
AB  - PURPOSE OF REVIEW: Because early findings indicated that native low-density
      lipoprotein (LDL) did not substantially increase macrophage cholesterol content
      during in-vitro incubations, investigators presumed that LDL must be modified in
      some way to trigger its uptake by the macrophage. The purpose of this review is
      to discuss recent findings showing that native unmodified LDL can induce massive
      macrophage cholesterol accumulation mimicking macrophage foam cell formation that
      occurs within atherosclerotic plaques. RECENT FINDINGS: Macrophages that show
      high rates of fluid-phase pinocytosis also show similar high rates of uptake of
      native unmodified LDL through nonreceptor mediated uptake within both
      macropinosomes and micropinosomes. Nonsaturable fluid-phase uptake of LDL by
      macrophages converts the macrophages into foam cells. Different macrophage
      phenotypes demonstrate either constitutive fluid-phase pinocytosis or inducible
      fluid-phase pinocytosis. Fluid-phase pinocytosis has been demonstrated by
      macrophages within mouse atherosclerotic plaques indicating that this pathway
      contributes to plaque macrophage cholesterol accumulation. SUMMARY: Contrary to
      what has been believed previously, macrophages can take up large amounts of
      native unmodified LDL by receptor-independent, fluid-phase pinocytosis converting
      these macrophages into foam cells. Thus, targeting macrophage fluid-phase
      pinocytosis should be considered when investigating strategies to limit
      macrophage cholesterol accumulation in atherosclerotic plaques.

PMID- 21881501
TI  - Innate immune recognition receptors and damage-associated molecular patterns in
      plaque inflammation.
AB  - PURPOSE OF REVIEW: To highlight critical advances achieved over the last year in
      the study of endogenous proatherogenic danger signals and corresponding molecular
      mechanism of innate immune signalling in atherosclerosis. RECENT FINDINGS: The
      identity and signalling mechanisms of LDL-derived inflammatory components are
      central in understanding the pathogenic role of modified LDL in the development
      of atherosclerosis. Studies in the preceding years have revealed LDL-derived
      phospholipids and cholesterol crystals as endogenous danger signals. These danger
      signals trigger Toll-like receptors and nucleotide-binding oligomerization domain
      like receptors inflammasome respectively, thereby instigating inflammatory
      responses and promoting disease progression. SUMMARY: Recent understandings of
      the causal role of LDL in atherosclerosis provide a new perspective on modified
      LDL-derived danger signals. These insights suggest dysregulated Toll-like
      receptor and nucleotide-binding oligomerization domain inflammasome signalling as
      an important mechanism underlying atherogenesis.

PMID- 21881503
TI  - Extracellular modifications of HDL in vivo and the emerging concept of
      proteolytic inactivation of prebeta-HDL.
AB  - PURPOSE OF REVIEW: Both quantity and quality of the circulating HDL particle
      matter for the optimal antiatherogenic potential of HDL. This review summarizes
      various mechanisms capable of inducing extracellular modifications of HDL and
      reducing the function of HDL subclasses as cholesterol acceptors. Special
      emphasis is laid on the proteolytic inactivation of lipid-poor prebeta-migrating
      HDL (prebeta-HDL). RECENT FINDINGS: HDL particles can undergo functional
      inactivation in vivo. During atherogenesis, different cell types in the arterial
      intima release enzymes into the intimal fluid, potentially capable of causing
      structural and chemical modifications of the various components present in the
      lipid core or in the polar surface of the HDL particles. Enzymatic oxidation,
      lipolysis and proteolysis, and nonenzymatic glycosylation are among the HDL
      modifications that adversely affect HDL functionality. Proteolysis of prebeta-HDL
      by various proteases present in the arterial intima has emerged as a potential
      mechanism that impairs the efficiency of HDL to promote cholesterol efflux from
      macrophage foam cells, the mast cell-derived neutral protease chymase being a
      prime example of such impairment. A paradigm of proteolytic inactivation of
      prebeta-HDL in vivo is emerging. SUMMARY: Several extracellular enzymes present
      in the arterial intima may compromise various cardioprotective functions of HDL.
      Observations on proteolysis of specific lipid-poor HDL subpopulations in vivo
      constitute the basis for future studies evaluating the actual impact of
      proteolytic microenvironments on the initiation and progression of
      atherosclerotic lesions.

PMID- 21881504
TI  - Whole exome and whole genome sequencing.
AB  - PURPOSE OF REVIEW: The purpose of this review is to describe the new DNA
      sequencing technologies referred to as next-generation sequencing (NGS). These
      new methods are becoming central to research in human disease and are starting to
      be used in routine clinical care. RECENT FINDINGS: Advances in instrumentation
      have dramatically reduced the cost of DNA sequencing. An individual's entire
      genome can now be sequenced for $7500. In addition, the software needed to
      analyze and help interpret this data is rapidly improving. This technology has
      been used by researchers to discover new genetic disorders and new disease
      associations. In the clinic, it can define the etiology in patients with
      undiagnosed genetic disorders and identify mutations in a cancer to help guide
      chemotherapy. SUMMARY: Here we discuss how whole-exome sequencing and whole
      genome sequencing are used in basic research and clinical care. These new
      techniques promise to speed research and affect how healthcare is delivered.

PMID- 21881502
TI  - The autoimmune concept of atherosclerosis.
AB  - PURPOSE OF REVIEW: This review summarizes the recent data on the 'Autoimmune
      Concept of Atherosclerosis', according to which the first stage of this disease
      is due to an autoimmune reaction against arterial endothelial cells expressing
      heat shock protein 60 (HSP60) and adhesion molecules when stressed by classical
      atherosclerosis risk factors. Special emphasis is put on oxidized low-density
      lipoproteins as early endothelial stressors. RECENT FINDINGS: Plasma cholesterol
      and LDL levels considered 'normal' by the medical community are possibly too high
      from an evolutionary viewpoint. The proinflammatory milieu at sites of early
      atherosclerotic lesions could be conducive to oxidation of LDL in situ. LDL
      oxidation can also take place at nonvascular sites or in the circulation under
      general proinflammatory conditions explaining its proatherosclerotic role in
      'normocholesterolemic' individuals. SUMMARY: We hypothesize that the plasma
      cholesterol and LDL levels currently considered normal are evolutionarily too
      high. Cholesterol and/or oxidized low-density lipoprotein, even as a mild HSP60
      inducing endothelial stressor, function as a ubiquitous risk factor. If this
      hypothesis is true, most members of developed societies might be at risk to
      develop atherosclerotic plaques at anti-HSP60-immunity-triggered intimal
      inflammatory foci, irrespective of the primary risk-factor(s).

PMID- 21881505
TI  - An update on influenza vaccination in patients with egg allergy.
AB  - PURPOSE OF REVIEW: Egg allergy is a common problem affecting young children
      especially. There has been much debate over the past several decades on how to
      approach the subject of influenza vaccination in children with egg allergy.
      RECENT FINDINGS: Because of concern regarding the egg protein content in the
      influenza virus vaccine, pediatricians have in the past typically taken a
      conservative approach of avoiding influenza vaccination in egg-allergic patients.
      Subsequently, it was shown that the influenza vaccine could be safely
      administered to patients who had negative skin testing to the vaccine. Most
      recently, studies have demonstrated a low risk of giving the vaccine either in
      divided doses or as a single dose in a controlled setting without the need for
      skin testing. SUMMARY: In considering vaccination in a patient with a history of
      egg allergy, several factors should be weighed, including the severity of the egg
      allergy, the egg content of vaccines, and the setting of vaccine administration.
      However, it appears that the risk of anaphylaxis to the influenza vaccine in
      patients with egg allergy may be much lower than previously thought, suggesting
      that in many cases skin testing may not be necessary.

PMID- 21881506
TI  - Surprised by echocardiography.

PMID- 21881507
TI  - Impact of congenital heart disease on fetal brain development and injury.
AB  - PURPOSE OF REVIEW: Advances in cardiac surgical techniques and intensive care
      have led to improved survival in babies with congenital heart disease (CHD).
      Although it is true that the majority of children with CHD today survive, many
      have impaired neurodevelopmental outcome. Although continuing to improve short
      term morbidity and mortality are important goals, recent research has focused on
      defining the impact of CHD on brain development and brain injury in utero. RECENT
      FINDINGS: The impact of CHD on the developing brain of the fetus and infant will
      be discussed. Neurologic abnormalities detectable prior to surgery will be
      described and postnatal progression of abnormalities will be highlighted.
      Potential causes of these findings will be discussed, including altered cerebral
      blood flow in utero, and brain development and risk for in-utero and postnatal
      brain injury. Finally, neurologic and developmental outcome after surgical repair
      of CHD will be reviewed. SUMMARY: Neurodevelopmental evaluation preoperatively
      and postoperatively in CHD patients should be standard practice, not only to
      identify those with impairments who would benefit from intervention services but
      also to identify risk factors and strategies to optimize outcome. Fetal
      management and intervention strategies for specific defects may ultimately play a
      role in improving in-utero hemodynamics and increasing cerebral oxygen delivery
      to enhance brain development.

PMID- 21881508
TI  - Intrauterine devices in adolescents.
AB  - PURPOSE OF REVIEW: The stubborn epidemic of teen pregnancy remains a major public
      health problem in the United States. This review discusses the use of
      intrauterine devices (IUDs) in United States teens as a potential strategy to
      reduce teen pregnancy. Traditionally, the IUD was not thought of as an
      appropriate teen contraceptive method. RECENT FINDINGS: Recently, IUDs have
      become a recommended contraceptive option for adolescent females. This change
      reflects an understanding of the safety of modern IUDs, the potential for this
      highly effective method to reduce teen pregnancy, and the promotion of this
      strategy in teens by national organizations/governmental agencies including the
      Centers for Disease Control and Prevention, the World Health Organization, and
      the American College of Obstetricians and Gynecologists. Current data do not
      support that IUDs affect long-term fertility or increase sexually transmitted
      diseases in teens. SUMMARY: IUDs are now considered by many experts as a first
      line contraceptive option for teens in the United States.

PMID- 21881509
TI  - Pulmonary exacerbations in cystic fibrosis.
AB  - PURPOSE OF REVIEW: The chronic infection and inflammation of cystic fibrosis (CF)
      lung disease causes a progressive decline of lung function resulting in daily
      symptoms such as cough and sputum production. There are intermittent episodes of
      acute worsening of symptoms, more commonly referred to as pulmonary
      exacerbations. Despite this being a common event, there is still no standardized
      definition of an exacerbation. A recent set of guidelines from the CF Foundation
      Pulmonary Therapies Committee on the treatment of exacerbations noted the paucity
      of data supporting commonly used therapies. This review describes our current
      understanding of pulmonary exacerbations and the therapies used to treat them.
      RECENT FINDINGS: The treatment of an exacerbation is intended to resolve the
      worsened symptoms and to restore the lung function that is commonly lost in the
      acute presentation. A most striking finding is the observation that for many
      patients there is no restoration of lung function, suggesting we either need
      better therapies to prevent exacerbations or better treatment of exacerbations.
      SUMMARY: We have established recommendations on specific treatment of a pulmonary
      exacerbation and have outlined the areas where we need better information on
      appropriate therapies. Once we have a standardized definition of an exacerbation,
      we can proceed with clinical trials of therapies specific for its treatment.

PMID- 21881510
TI  - Liver disease in cystic fibrosis.
AB  - PURPOSE OF REVIEW: This review looks at what is currently known about liver
      disease in cystic fibrosis (CF) in light of the literature over the past year,
      and what the ongoing challenges are from a clinical and research perspective for
      the optimal management of cystic fibrosis liver disease (CFLD). RECENT FINDINGS:
      Patients with CF who develop clinically significant liver disease have a worse
      overall phenotype, and whereas there is no definite evidence that they have a
      shorter life expectancy, longer follow-up is required to determine if liver
      disease is a risk factor for mortality in CF.The development of the ferret and
      pig animal models of CF with multiorgan involvement is an important breakthrough
      which will enhance our understanding of the pathogenesis of CFLD, and with which
      it is hoped novel therapeutic targets for the treatment of CFLD will be
      identified. SUMMARY: Whereas there is still no effective treatment for liver
      disease in CF, recent developments of animal models of CFLD will enhance our
      capacity to develop new therapeutic targets and reduce the impact of liver
      disease on mortality in CF.

PMID- 21881511
TI  - Treating obstructive sleep apnea with hypoglossal nerve stimulation.
AB  - PURPOSE OF REVIEW: Obstructive sleep apnea (OSA) is a common disorder
      characterized by recurrent pharyngeal collapse secondary to sleep-induced
      hypotonia of peri-pharyngeal structures. Therapy for OSA is sometimes poorly
      tolerated and not always effective. The current study reviews a new treatment
      modality, hypoglossus stimulation, recently evaluated by multiple physiological
      studies and currently assessed by several clinical studies. RECENT FINDINGS: A
      phase-I, implantable hypoglossus nerve stimulation multicenter study was
      published in 2001. Significant reduction in apnea-hypopnea index (AHI) was
      reported in seven of the eight implanted OSA patients, but technical faults
      precluded prolonged follow-up. Over the past 2 years, three new hypoglossus nerve
      stimulation systems have been evaluated in more than 60 OSA patients. In
      adequately selected patients, a more than 50% reduction in AHI was observed.
      Usually, a decrease in OSA severity from moderate-severe to mild-minimal can be
      achieved. SUMMARY: Ongoing research, including recent initiation of a large
      multicenter phase-III study, suggests that hypoglossus nerve stimulators are
      likely to be available as a new treatment modality within a few years. Additional
      data are needed to define which OSA patients are most likely to benefit from
      hypoglossus nerve stimulation. Continuous refinement of electrodes design is
      likely to improve stimulation efficacy in coming years.

PMID- 21881512
TI  - Testing sleepiness and vigilance in the sleep laboratory.
AB  - PURPOSE OF REVIEW: Excessive daytime sleepiness (EDS) is common and a potentially
      devastating public health challenge. EDS has been implicated as a contributing
      factor to workplace injury, motor vehicle accidents, cardiovascular disease, and
      impaired quality of life. Subjective self-report measures have failed to
      sufficiently quantify EDS. The use of objective tools found in sleep laboratories
      is therefore fundamental in the management of patients with EDS. The purpose of
      this review is to provide an overview of the current methods used to quantify
      sleepiness, and to highlight recent advances. RECENT FINDINGS: The Multiple Sleep
      Latency Test (MSLT), normally used for the diagnosis of narcolepsy, can be a
      useful tool in recognizing other forms of sleepiness. The Maintenance of
      Wakefulness Test (MWT) has also been confirmed as an important test to identify
      EDS, as well as to provide an indicator of future risk of accidents.
      Modifications and newer tests have been discussed with potential applications for
      the future. SUMMARY: Objective tests such as the MSLT and MWT are useful in the
      diagnosis and management of patients with EDS. However, the relatively high cost
      can restrict their overall usefulness in clinical medicine. Newer simple tests
      are under development.

PMID- 21881513
TI  - The use of a cystic fibrosis patient registry to assess outcomes and improve
      cystic fibrosis care in Germany.
AB  - PURPOSE OF REVIEW: Cystic fibrosis (CF) patient registries have become an
      important epidemiological tool for demography, networking, and quality
      management. This review describes recent developments in patient registries,
      outcome research, and pilot projects in quality improvement. RECENT FINDINGS:
      National and international CF registry efforts have been producing consolidated
      data. Classical outcome indicators describing nutritional status and lung
      function are now being used in a more precise way, based on body mass index
      percentiles and longitudinal data. Projects involving single centers and quality
      groups, such as the German benchmarking project, have been showing that quality
      improvement is possible and that negative developments do not necessarily have to
      be accepted in CF. SUMMARY: CF provides a model of the link between healthcare
      delivery and outcomes in patients. CF registry data can be used to improve
      quality in CF healthcare. Quality improvement is a continuous endeavor involving
      the reinforcement of standards and programs as well as individual attitudes and
      soft skills. One particularly powerful technique is benchmarking, that is,
      learning from the best.

PMID- 21881514
TI  - The role of exercise in maintaining health in cystic fibrosis.
AB  - PURPOSE OF REVIEW: Consensus statements about the care of people with cystic
      fibrosis (CF) recommend exercise as part of a wider management strategy. Many of
      these recommendations are based on high-quality evidence that regular exercise
      improves some important clinical outcomes, such as lung function and quality of
      life. However, the evidence about the effect of exercise on other clinical
      outcomes is less extensive or lower in quality. This article will review the
      physiological effects of exercise on a range of outcomes in people with CF, the
      mechanisms by which exercise may improve these outcomes and the quality and
      findings of clinical research into the effects of exercise in the management of
      CF. RECENT FINDINGS: Substantial evidence confirms that exercise significantly
      reduces the rate of decline in lung function in people with CF, at least in part
      by increasing mucus clearance. Regular exercise training over 6 months improves
      aerobic exercise capacity. Bone health is often poor in people with CF, but only
      indirect evidence supports that increasing the amount of exercise will have a
      beneficial effect on bone density. CF-related diabetes is also a common sequela
      of the disease, but again only evidence from type-2 diabetes exists to support
      exercise as a way of managing it. SUMMARY: Although its effects on some outcomes
      are unclear, the overall effect of exercise on quality of life is substantially
      beneficial and the evidence available for other specific outcomes is directly or
      indirectly supportive, so it appears appropriate to recommend it in clinical
      practice.

PMID- 21881515
TI  - Hypertension and risk of renal cell carcinoma among white and black Americans.
AB  - BACKGROUND: Renal cell carcinoma and hypertension (a well-established renal
      cancer risk factor) are both more frequent among blacks than whites in the United
      States. The association between hypertension and renal cell carcinoma has not
      been examined in black Americans. We investigated the hypertension-renal cancer
      association by race, and we assessed the role of hypertension in the racial
      disparity of renal cancer incidence. METHODS: Participants were enrolled in a
      population-based case-control study in Detroit and Chicago during 2002-2007
      (number of cases: 843 whites, 358 blacks; number of controls: 707 whites, 519
      blacks). Participants reported their history of hypertension and antihypertensive
      drug use. We used unconditional logistic regression to calculate odds ratios
      (ORs) and 95% confidence intervals (CIs), adjusted for demographic
      characteristics, smoking, body mass index, and family history of cancer. RESULTS:
      Hypertension doubled renal cancer risk (OR = 2.0 [CI = 1.7-2.5]) overall. For
      whites, the OR was 1.9 (CI = 1.5-2.4), whereas for blacks it was 2.8 (2.1-3.8) (P
      for interaction = 0.11). ORs increased with time after hypertension diagnosis (P
      for trend <0.001), reaching 4.1 (CI = 2.3-7.4) for blacks and 2.6 (CI = 1.7-4.1)
      for whites after 25 years. ORs for poorly controlled hypertension were 4.5 (CI =
      2.3-8.8) for blacks and 2.1 (CI = 1.2-3.8) for whites. If these estimates
      correctly represent causal effects and if, hypothetically, hypertension could be
      prevented entirely among persons aged 50-79 years, the black/white disparity in
      renal cancer could be reversed among women and reduced by two-thirds among men.
      CONCLUSIONS: Hypertension is a risk factor for renal cancer among both blacks and
      whites, and might explain a substantial portion of the racial disparity in renal
      cancer incidence. Preventing and controlling hypertension might reduce renal
      cancer incidence, adding to the known benefits of blood pressure control for
      heart disease and stroke reduction, particularly among blacks.

PMID- 21881516
TI  - Identification and treatment of bisphosphonate-associated actinomycotic
      osteonecrosis of the jaws.
AB  - Osteonecrosis of the jaws (ONJ) is a condition characterized by necrotic exposed
      bone in the jaws of patients receiving intravenous or oral bisphosphonate
      therapy. A review of the medical and dental literature reveals that the
      pathoetiology of ONJ remains unknown and there is no established link that
      bisphosphonates are the primary cause of this bone pathology. However, there is
      clinical evidence that Actinomyces may play a critical role in the pathogenesis
      of bisphosphonate-associated ONJ. Identification and a prolonged course of oral
      antimicrobial therapy may lead to complete resolution of this actinomycotic
      osteonecrosis.

PMID- 21881517
TI  - Fatigue resistance of 2 different CAD/CAM glass-ceramic materials used for single
      tooth implant crowns.
AB  - PURPOSE: To evaluate the fatigue resistance of 2 different CAD/CAM in-office
      monoceramic materials with single-tooth implant-supported crowns in functional
      area. MATERIALS AND METHODS: A metal experimental model with a dental implant was
      designed to receive in-office CAD/CAM-generated monoceramic crowns. Laterally
      positioned axial dynamic loading of 300 N at 2 Hz was applied to implant
      supported crowns machined from 2 different glass materials for 100,000 cycle.
      Failures in terms of fracture, crack formation, and chipping were macroscopically
      recorded and microscopically evaluated. RESULTS: Four of 10 aluminasilicate glass
      ceramic crowns fractured at early loading cycles, the rest completed loading with
      a visible crack formation. Crack formation was recorded for 2 of 10 leucite glass
      ceramic crowns. Others completed test without visible damage but fractured upon
      removal. DISCUSSION: Lack in chemical adhesion between titanium abutment and
      dental cement likely reduces the fatigue resistance of machinable glass-ceramic
      materials. However, relatively better fractural strength of leucite glass
      ceramics could be taken into consideration. Accordingly, progress on
      developmental changes in filler composition of glass-ceramics may be promising.
      CONCLUSION: Machinable glass-ceramics do not possess sufficient fatigue
      resistance for single-tooth implant crowns in functional area.

PMID- 21881518
TI  - Temperature increase during CO(2) and Er:YAG irradiation on implant surfaces.
AB  - PURPOSE: The purpose of this study was to evaluate the temperature gradient
      (DeltaT) generated by laser irradiation of an implant surface using a carbon
      dioxide (CO(2)) and an Erbium:yttrium aluminium garnet (Er:YAG) laser. MATERIALS
      AND METHODS: A dental implant was irradiated with a CO(2) and an Er:YAG lasers,
      with variable power settings. Temperature increase was measured in 2 locations of
      the implant surface: in the cervical area (DeltaT(c)) and in the apical area
      (DeltaT(a)). RESULTS: The CO(2) laser showed the following results: after 60
      seconds of irradiation with continuous mode, DeltaT(c) was 13.9 degrees C and
      DeltaTa was 12.5 degrees C. The Er:YAG laser showed the following results: after
      60 seconds of irradiation with continuous mode, the temperature rise DeltaT(c)
      was 50.6 degrees C and DeltaT(a) was 38.6 degrees C. The CO(2) laser with
      continuous mode generated a temperature increase of 10 degrees C after only 36
      seconds. The Er:YAG laser with continuous mode produced a more rapid temperature
      increase and took only 10 seconds to reach the critical threshold. CONCLUSIONS:
      The irradiation of implant surfaces with CO(2) and Er:YAG lasers may produce a
      temperature increase above the critical threshold (10 degrees C) after 10 seconds
      of continuous irradiation.

PMID- 21881519
TI  - Bone regeneration in the maxillary sinus using an autologous fibrin-rich block
      with concentrated growth factors alone.
AB  - PURPOSE: The purpose of this study was to evaluate the predictability of new bone
      formation in the maxillary sinus using an autologous fibrin-rich blocks with
      concentrated growth factors (CGFs) alone as an alternative to graft material.
      MATERIALS AND METHODS: A total of sixty-one sinus grafts were consecutively
      performed using the lateral window approach. After making replaceable bony
      window, the sinus membrane was elevated to make a new compartment. After 113
      implants (average 13 mm high) with 11 different systems were placed
      simultaneously, the collected fibrin-rich blocks with CGFs alone were inserted in
      the sinus. To seal the lateral window, the bony window was repositioned.
      Radiographic, clinical, and histologic evaluation was performed to verify sinus
      augmentation. RESULTS: No significant postoperative complications developed. New
      bone consolidation in all augmented maxillary sinus was observed along the
      implants on plain radiographs and on cone-beam computed tomograms. The success
      rate of implant was 98.2% after an average of 10 months loading. CONCLUSION:
      Fibrin-rich blocks with CGFs act as an alternative to bone grafting and can be a
      predictable procedure for sinus augmentation.

PMID- 21881520
TI  - The association of albuminuria, arterial stiffness, and blood pressure status in
      nondiabetic, nonhypertensive individuals.
AB  - OBJECTIVE: Although several studies have reported an association between
      microalbuminuria and pulse wave velocity in patients with hypertension or
      diabetes, there have been no reports of their significance in apparently healthy
      individuals. METHODS: Microalbuminuria and brachial-ankle PWV (baPWV) were
      investigated in a sample of 3826 nonhypertensive, nondiabetic individuals (3598
      men, mean age 50 +/- 11.3 years) at Kangbuk Samsung Health Promotion Center
      between 2006 and 2009. The patients were classified into two groups according to
      urinary albumin-creatinine ratio (UACR) in morning urine specimens:
      normoalbuminuria (<30 MUg/mg) and microalbuminuria (30-300 MUg/mg). RESULTS: The
      prevalence of prehypertension (preHT) and microalbuminuria was 52.5 and 4%,
      respectively. Abnormal baPWV and microalbuminuria each has unfavorable
      cardiometabolic profile. The absolute values of baPWV were correlated with those
      of UACR (r = 0.220, P < 0.001). In multivariate regression analysis, the
      microalbuminuria group showed an independent association of increasing baPWVs
      irrespective of potential confounders, compared with the normoalbuminuria group
      (standard beta = 0.049, P < 0.001). In the subspecified analyses, category III
      (preHT + normoalbuminuria) and IV (preHT + microalbuminuria) had higher odds
      ratio (ORs) [95% confidence interval (CI)] for the abnormal baPWV group, compared
      with category I (normal BP + normoalbuminuria) [2.345 (2.010-2.735) and 3.822
      (2.367-6.171), respectively]. CONCLUSION: These findings demonstrate
      epidemiologic evidence for an independent association between arterial stiffness
      and microalbuminuria, indices of subclinical target organ damage in
      nonhypertensive, nondiabetic individuals, which suggests the possibility of a
      similar pathophysiologic mechanism involved in these two indices of subclinical
      target organ damage.

PMID- 21881521
TI  - Evaluation of a direct prorenin assay making use of a monoclonal antibody
      directed against residues 32-39 of the prosegment.
AB  - BACKGROUND: Prorenin is an early marker of microvascular complications in
      diabetes. However, it can only be measured indirectly (following its conversion
      to renin), with a renin immunoradiometric assay (IRMA). Unfortunately, treatment
      with a renin inhibitor interferes with this assay, because renin inhibitors
      induce a conformational change in prorenin, thereby allowing its detection as
      renin. METHODS: We evaluated Molecular Innovation's new direct prorenin ELISA,
      which makes use of an antibody that recognizes an epitope near prorenin's
      putative cleavage site (R 43 L 44), thus no longer requiring prorenin activation.
      Plasma samples of 41 diabetic individuals treated with aliskiren (renin
      inhibitor) or irbesartan were tested. Semi-purified recombinant prorenin was used
      as standard, because the ELISA standard yielded approximately 10-fold lower
      values in the renin IRMA following its conversion to renin. RESULTS: The ELISA
      detected prorenin levels that were identical to those determined by the IRMA in
      untreated and irbesartan-treated individuals. Yet, it yielded higher prorenin
      levels in aliskiren-treated individuals. Aliskiren, at levels reached in plasma
      during treatment, did not interfere with the ELISA, but allowed the detection of
      up to 20-30% of prorenin as renin in the IRMA, thereby resulting in a significant
      overestimation of renin and an underestimation of prorenin. The ELISA rendered
      results within 2 h and did not require a pretreatment period of several days to
      convert prorenin to renin. CONCLUSION: The new direct assay allows rapid prorenin
      detection, is not hampered by aliskiren when used at clinically relevant doses,
      and might be used to identify diabetic patients developing retinopathy and/or
      nephropathy.

PMID- 21881522
TI  - Association of ATP1B1, RGS5 and SELE polymorphisms with hypertension and blood
      pressure in African-Americans.
AB  - OBJECTIVE: Although an increasing number of hypertension-associated genetic
      variants is being reported, replication of these findings in independent studies
      has been challenging. Several genes in a human chromosome 1q linkage region have
      been reported to be associated with hypertension. We examined polymorphisms in
      three of these genes (ATP1B1, RGS5 and SELE) in relation to hypertension and
      blood pressure in a cohort of African-Americans. METHODS: We genotyped 87 single
      nucleotide polymorphisms (SNPs) from the ATP1B1, RGS5 and SELE genes in a well
      characterized cohort of 968 African-Americans and performed a case-control study
      to identify susceptibility alleles for hypertension and blood pressure
      regulation. Single SNP and haplotype association testing was done under an
      additive genetic model with adjustment for age, sex, BMI and ancestry-by-genotype
      (principal components). RESULTS: A total of 12 SNPs showed nominal association
      with hypertension and/or blood pressure. The strongest signal for hypertension
      was for rs2815272 in the RGS5 gene (P = 9.3 * 10). For SBP, rs3917420 in the SELE
      gene (P = 9.0 * 10) and rs4657251 in the RGS5 gene (P = 9.7 * 10) were the top
      hits. Effect size for each of these variants was approximately 2-3 mmHg. A five
      SNP haplotype in the SELE gene also showed significant association with SBP after
      correction for multiple testing (P < 0.01). CONCLUSION: These findings provide
      additional support for the genetic role of ATP1B1, RGS5 and SELE in hypertension
      and blood pressure regulation.

PMID- 21881523
TI  - Birth weight, weight change, and blood pressure during childhood and adolescence:
      a school-based multiple cohort study.
AB  - OBJECTIVE: We assessed the association between birth weight, weight change, and
      current blood pressure (BP) across the entire age-span of childhood and
      adolescence in large school-based cohorts in the Seychelles, an island state in
      the African region. METHODS: Three cohorts were analyzed: 1004 children examined
      at age 5.5 and 9.1 years, 1886 children at 9.1 and 12.5, and 1575 children at
      12.5 and 15.5, respectively. Birth and 1-year anthropometric data were gathered
      from medical files. The outcome was BP at age 5.5, 9.1, 12.5 or 15.5 years,
      respectively. Conditional linear regression analysis was used to estimate the
      relative contribution of changes in weight (expressed in z-score) during
      different age periods on BP. All analyses were adjusted for height. RESULTS: At
      all ages, current BP was strongly associated with current weight. Birth weight
      was not significantly associated with current BP. Upon adjustment for current
      weight, the association between birth weight and current BP tended to become
      negative. Conditional linear regression analyses indicated that changes in weight
      during successive age periods since birth contributed substantially to current BP
      at all ages. The strength of the association between weight change and current BP
      increased throughout successive age periods. CONCLUSION: Weight changes during
      any age period since birth have substantial impact on BP during childhood and
      adolescence, with BP being more responsive to recent than earlier weight changes.

PMID- 21881524
TI  - Inappropriately high left ventricular mass in patients with type 2 diabetes
      mellitus and no overt cardiac disease. The DYDA study.
AB  - BACKGROUND: An inappropriately high left ventricular mass (iLVM) may be detected
      in patients with diabetes mellitus. Several hemodynamic and nonhemodynamic
      factors stimulating LVM growth may actively operate in these patients. In this
      study, we assessed prevalence and factors associated with iLVM in patients with
      diabetes mellitus. METHODS: We analyzed baseline data from 708 patients (61 +/- 7
      years, 57% treated for hypertension) with type 2 diabetes mellitus without
      evidence of cardiac disease enrolled in the left ventricular dysfunction in
      diabetes study. iLVM was diagnosed by Doppler echocardiography as LVM more than
      28% of the expected LVM predicted from height, sex and stroke work. RESULTS: iLVM
      was detected in 166 patients (23%), irrespective of concomitant hypertension.
      Patients with iLVM were more frequently women, had higher BMI and prevalence of
      metabolic syndrome, higher serum triglyceride levels and were treated more
      frequently with metformin and diuretics. In a multivariate model, female sex
      [odds ratio (OR) 1.502 (95% confidence interval (CI) 1.010-2.231), P = 0.04],
      higher serum triglyceride levels [OR 1.007 (95% CI 1.003-1.012), P < 0.001] and
      BMI [OR 1.220 (95% CI 1.116-1.335), P < 0.001] emerged independently related to
      iLVM. CONCLUSION: iLVM is detectable in about a quarter of patients with type 2
      diabetes mellitus without evidence of cardiac disease and is unrelated to blood
      pressure levels. The association between LVM and some components of metabolic
      syndrome in these patients may have important practical implications.

PMID- 21881525
TI  - Relatively lower central aortic pressure in patients with impaired insulin
      sensitivity and resistance: the Toon Health Study.
AB  - OBJECTIVE: Central aortic blood pressure (BP) has been postulated to correlate
      more closely with cardiovascular disease risk than brachial cuff BP. However, the
      effect of insulin sensitivity and resistance on central BP is not fully
      understood. Here, we evaluated the associations between insulin
      sensitivity/resistance and central BP using the oral glucose tolerance test.
      METHODS: A total of 1034 Japanese participants were enrolled in this study. The
      absolute pressure of the late systolic peak (SBP2) of the brachial BP obtained by
      the radial waveform was considered to be the central systolic BP. Oral glucose
      tolerance test was performed by administering 75 g of glucose, and blood samples
      were obtained at 0, 60, 120 min after glucose loading. RESULTS: Mean SBP2 was
      found to be lower than mean brachial systolic BP (SBP) (119 +/- 20, 126 +/- 19
      mmHg, P < 0.001), and differences between SBP and SBP2 were significantly larger
      in patients with reduced insulin sensitivity (-8.2 +/- 5.2, -7.2 +/- 5.3, -7.1 +/
      5.1, and -6.5 +/- 4.9 mmHg, in the first, second, third and fourth quartiles,
      respectively; P = 0.002) and increased insulin resistance (-6.6 +/- 5.1, -6.6 +/-
      4.8, -7.3 +/- 4.8, -8.5 +/- 5.6 mmHg, P < 0.001). Multiple linear regression
      analysis identified reduced insulin sensitivity (beta = 0.067, P = 0.033) and
      increased insulin resistance (beta = -0.081, P = 0.009) as independent
      determinants of the difference between SBP and SBP2. CONCLUSION: Given that both
      insulin sensitivity and insulin resistance were found to be significant
      determinants of the difference between SBP and SBP2 in a healthy general
      population, we suggest measuring the SBP2 in individuals with impaired insulin
      action in order to accurately assess their risk of developing cardiovascular
      disease.

PMID- 21881526
TI  - Angiotensin-II and rosuvastatin influence matrix remodeling in human mesangial
      cells via metalloproteinase modulation.
AB  - OBJECTIVE: Persistent inflammation and oxidative stress influence the progression
      of diabetic nephropathy. Metalloproteinases (MMPs) participate in extracellular
      matrix remodeling. Statins show favorable anti-inflammatory effects in chronic
      kidney disease. We evaluated the effect of rosuvastatin on inflammatory and pro
      fibrotic responses due to exposure to different glucose or free fatty acid (FFA)
      concentrations. METHODS: Human mesangial cells (HMCs) grown at 5.5 (normal
      glucose) or 22 mmol/l (high glucose) glucose or exposed to FFA were treated with
      angiotensin-II in the presence or absence of rosuvastatin. We measured MMP-2, MMP
      9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 expression and
      activity, and quantified the fibrotic factors transforming growth factor-beta1
      (TGF-beta1), fibronectin, and collagen IV. RESULTS: At normal glucose,
      angiotensin-II induced a dose-dependent downregulation of MMP-2; rosuvastatin
      reversed this effect. On the contrary, TIMP-2 and MMP-9 were upregulated by
      angiotensin-II and downregulated by rosuvastatin; the effects on TIMP-1 were
      negligible. Some of the angiotensin-II effects were potentiated in the presence
      of high glucose and FFA; under both conditions, rosuvastatin was able to reverse
      these effects. MMP-2 and MMP-9 activity followed the same trend of expression,
      with rosuvastatin able to upregulate MMP-2 activity. The modulation of the
      MMP/TIMP system was paralleled by an increase in TGF-beta1, fibronectin, and
      collagen-IV; all were reduced by rosuvastatin treatment. Silencing the MMP-2 gene
      confirmed its role in modulating some of these angiotensin-II effects.
      CONCLUSION: Angiotensin-II induces a pro-fibrotic response in HMCs mainly via a
      dysregulation of the MMP-2/TIMP-2 pattern. This effect, partially amplified in
      the presence of high glucose and FFA, is reversed by rosuvastatin, suggesting
      another potential therapeutic application for this 3-hydroxy-3-methylglutaryl
      coenzyme A reductase inhibitor.

PMID- 21881527
TI  - Left atrial size in hypertension and stroke.
AB  - INTRODUCTION: An enlarged left atrium is associated with increased risk for
      stroke. However, there are controversies regarding how left atrial size should be
      measured. MATERIAL AND METHODS: Echocardiography and carotid artery ultrasound
      were performed in 120 patients with essential hypertension (HT group) and in 64
      hypertensive patients admitted with a first-ever ischemic stroke (HT-stroke
      group). Left atrial size was measured as antero-posterior diameter (LAD) and as
      left atrial volume (LAV) and indexed to body surface area (LADi/LAVi). All
      patients were in sinus rhythm and without mitral valve disease. RESULTS: In the
      HT-stroke group, LAVi and LADi were significantly larger as compared with the HT
      group (P <= 0.03 for all). In bivariate correlations, larger left atrial size was
      associated with higher SBPs and DBPs and significant carotid artery stenosis both
      in HT and HT-stroke groups (all P < 0.05). In multivariate logistic regression
      analysis, stroke was associated significantly with larger LAVi [odds ratio (OR)
      1.73, 95% confidence interval (CI) 1.06-2.65]; left ventricular mass index (OR
      1.11, 95% CI 1.03-1.21); significant carotid artery stenosis (OR 1.09, 95% CI
      1.03-1.24); and any carotid artery stenosis (OR 1.07, 95% CI 1.03-1.14). Analysis
      of receiver operating characteristic curves revealed that LAVi was the best left
      atrial measurement for prediction of stroke (OR 0.77, 95% CI 0.70-0.84).
      CONCLUSION: In hypertensive patients, a first-ever ischemic stroke was associated
      with larger left atrial size, left ventricular mass index and internal carotid
      artery stenosis. LAVi was the left atrial measurement most closely associated
      with ischemic stroke.

PMID- 21881528
TI  - Baseline predictors of resistant hypertension in the Anglo-Scandinavian Cardiac
      Outcome Trial (ASCOT): a risk score to identify those at high-risk.
AB  - BACKGROUND: Resistant hypertension is a well recognized clinical entity, which
      has been inadequately researched to date. METHODS: A multivariable Cox model was
      developed to identify baseline predictors of developing resistant hypertension
      among 3666 previously untreated Anglo-Scandinavian Cardiac Outcome Trial (ASCOT)
      patients and construct a risk score to identify those at high risk. Secondary
      analyses included evaluations among all 19 257 randomized patients. RESULTS: One
      third (1258) of previously untreated, and one-half (9333) of all randomized
      patients (incidence rates 75.2 and 129.7 per 1000 person-years, respectively)
      developed resistant hypertension during a median follow-up of 5.3 and 4.8 years,
      respectively. Increasing strata of baseline SBP (151-160, 161-170, 171-180, and
      >180 mmHg) were associated with increased risk of developing resistant
      hypertension [hazard ratio 1.24 (95% confidence interval, CI 0.81-1.88), 1.50
      (1.03-2.20), 2.15 (1.47-3.16), and 4.43 (3.04-6.45), respectively]. Diabetes,
      left ventricular hypertrophy, male sex, and raised BMI, fasting glucose, and
      alcohol intake were other significant determinants of resistant hypertension.
      Randomization to amlodipine +/- perindopril vs. atenolol +/- thiazide [0.57 (0.50
      0.60)], previous use of aspirin [0.78 (0.62-0.98)], and randomization to
      atorvastatin vs. placebo [0.87 (0.76-1.00)] significantly reduced the risk of
      resistant hypertension. Secondary analysis results were similar. The risk score
      developed allows accurate risk allocation (Harrell's C-statistic 0.71), with
      excellent calibration (Hosmer-Lemeshow chi statistics, P = 0.99). A 12-fold (8.4
      17.4) increased risk among those in the highest vs. lowest risk deciles was
      apparent. CONCLUSION: Baseline SBP and choice of subsequent antihypertensive
      therapy were the two most important determinants of resistant hypertension in the
      ASCOT population. Individuals at high risk of developing resistant hypertension
      can be easily identified using an integer-based risk score.

PMID- 21881529
TI  - Higher muscle performance in adolescents compared with adults after a resistance
      training session with different rest intervals.
AB  - The aim of the present study was to compare the effect of 3 different rest
      intervals between sets on the total training volume, number of repetitions,
      ratings of perceived exertion (RPE), and resistance to fatigue in adolescents and
      adults during a resistance training session in the isoinertial chest press
      exercise. Fifteen male adolescents (15.2 +/- 1.2 years; 20.7 +/- 2.0 kg.m(-2);
      Tanner -4; 61.5 +/- 8.9, 10 repetition maximum [RM]) and 15 adults (22.2 +/- 2.7
      years; 23.3 +/- 2.0 kg.m(-2); Tanner -5; 84.3 +/- 13.5, 10RM) without previous
      experience with resistance training participated in the study. After 10RM test
      retest on 3 different occasions, participants were randomly assigned to a
      resistance training protocol with 30-, 60-, and 120-second rest interval between
      sets. The protocol consisted of 3 sets with 10RM. In all studied variables, with
      exception to total training volume and RPE, adolescents presented superior
      results as compared with adults (p < 0.001). On the other hand, both adults and
      adolescents exhibited a higher resistance to fatigue, total training volume, and
      number of repetitions with a longer rest interval (120 > 60 > 30 seconds) (p <
      0.01). Thus, these results indicate that adolescents present a higher recovery
      capacity between sets in a resistance training session than adults and a longer
      rest interval results in a higher number of repetitions completed, total training
      volume, and resistance to fatigue.

PMID- 21881530
TI  - Effects of an 18-week strength training program on low-handicap golfers'
      performance.
AB  - The purpose of this study was to determine the effects of an 18-week strength
      training program on variables related to low-handicap golfers' performance. Ten
      right-handed male golfers, reporting a handicap of 5 or less, were randomly
      divided into two groups: the control group (CG) (N = 5, age: 23.9 +/- 6.7 years)
      and the treatment group (TG) (N = 5, age: 24.2 +/- 5.4 years). CG players
      followed the standard physical conditioning program for golf, which was partially
      modified for the TG. The TG participated in an 18-week strength training program
      divided into three parts: maximal strength training including weightlifting
      exercises (2 days a week for 6 weeks), explosive strength training with combined
      weights and plyometric exercises (2 days a week for 6 weeks), and golf-specific
      strength training, including swings with a weighted club and accelerated swings
      with an acceleration tubing system (3 days a week for 6 weeks). Body mass, body
      fat, muscle mass, jumping ability, isometric grip strength, maximal strength
      (RM), ball speed, and golf club mean acceleration were measured on five separate
      occasions. The TG demonstrated significant increases (p < 0.05) in maximal and
      explosive strength after 6 weeks of training and in driving performance after 12
      weeks. These improvements remained unaltered during the 6-week golf-specific
      training period and even during a 5-week detraining period. It may be concluded
      that an 18-week strength training program can improve maximal and explosive
      strength and these increases can be transferred to driving performance; however,
      golfers need time to transfer the gains.

PMID- 21881531
TI  - Optimizing power output by varying repetition tempo.
AB  - The effects of varying interrepetition rest and eccentric velocity on power
      output (PO) and the number of repetitions performed during a bench press set were
      examined in 24 college-aged resistance trained men. On 6 separate occasions,
      subjects performed a set of bench press at 80% 1 repetition maximum until
      volitional fatigue. For each of the 6 repetition tempo trials, the bench press
      set was paced by metronome to a unique repetition tempo involving a combination
      of the following: interrepetition rest of 0 or 4 seconds; eccentric velocity of 1
      or 4 seconds and bottom rest of 0 or 3 seconds. The velocity of concentric
      contraction was maximal during all 6 tempo trials. During each trial, video data
      were captured to determine PO variables and number of successful repetitions
      completed at each tempo. One-way repeated measures analysis of variance showed
      tempos with a fast eccentric phase (1 second), and no bottom rest produced
      significantly greater (p <= 0.05) PO and repetitions than tempos involving slower
      eccentric velocity (4 seconds) or greater bottom rest (4 seconds). This
      combination of greater repetitions and PO resulted in a greater volume of work.
      Varying interrepetition rest (1 or 4 seconds) did not significantly affect PO or
      repetitions. The results of this study support the use of fast eccentric speed
      and no bottom rest during acute performance testing to maximize PO and number of
      repetitions during a set of bench press.

PMID- 21881532
TI  - Effects of dynamic warm-up on lower body explosiveness among collegiate baseball
      players.
AB  - Debate exists between the benefits and effectiveness of a dynamic warm-up vs. a
      static warm-up. This study was conducted to compare dynamic and static warm-ups
      on lower body explosiveness as measured by stationary vertical jump (VJ) and
      standing long jump (LJ) among collegiate baseball players. Participants (n = 17;
      age = 19.59 +/- 1.37 years) progressed through 3 different warm-ups on weekly
      testing dates over a 7-week period. After the warm-up routines, participants were
      measured for VJ height and LJ distance in centimeters. The mean jump heights for
      VJ were 66.49 +/- 8.28 cm for dynamic, 61.42 +/- 7.51 cm for static, and 62.72 +/
      7.84 cm for the control condition. The mean jump distances for LJ were 231.99 +/
      20.69 cm for dynamic, 219.69 +/- 20.96 cm for static, and 226.46 +/- 20.60 cm
      for the control. Results indicated that the participants jumped significantly
      higher in both experimental conditions while under the influence of the dynamic
      warm-up (VJ-F = 22.08; df = 1.33, 21.345; p < 0.00 and LJ-F = 32.20; df = 2, 32;
      p < 0.01). Additional LJ analysis determined that individuals jumped
      significantly further after no warm-up compared to after a static warm-up (-6.78,
      p < 0.05). Lower body explosiveness is critical in baseball and many other sports
      as well. The results show that dynamic warm-up increases both VJ height and LJ
      distance. Specifically, these findings indicate that athletes could gain nearly 2
      in. on his or her vertical jump by simply switching from a static warm-up routine
      to a dynamic routine.

PMID- 21881533
TI  - Sun-dried raisins are a cost-effective alternative to Sports Jelly Beans in
      prolonged cycling.
AB  - The purpose of this study was to examine the effects of a natural carbohydrate
      (CHO) source in the form of sun-dried raisins (SDRs) vs. Sports Jelly BeansTM
      (SJBs) on endurance performance in trained cyclists and triathletes. Ten healthy
      men (18-33 years) completed 1 water-only acclimatization exercise trial and 2
      randomized exercise trials administered in a crossover fashion. Each trial
      consisted of a 120-minute constant-intensity glycogen depletion period followed
      by a 10-km time trial (TT). During each experimental trial, participants consumed
      isocaloric amounts of SDRs or SJBs in 20-minute intervals. Measurements included
      time to complete 10-km TT, power output during 10-km TT, blood glucose levels and
      respiratory exchange ratio during glycogen depletion period, rate of perceived
      exertion (RPE), 'flow' questionnaire responses, and a hedonic (i.e.,
      pleasantness) sensory acceptance test. There were no significant differences in
      endurance performance for TT time (SDRs vs. SJBs, 17.3 +/- 0.4 vs. 17.3 +/- 0.4
      seconds) or power (229.3 +/- 13.0 vs. 232.0 +/- 13.6 W), resting blood glucose
      levels (5.8 +/- 04 mmol.L(-1) for SDRs and 5.4 +/- 0.2 mmol.L(-1) for SJBs), RPE,
      or flow experiences between SDR and SJB trials. However, the mean sensory
      acceptance scores were significantly higher for the SDRs compared to the SJBs
      (50.7 +/- 1.7 vs. 44.3 +/- 2.7). Consuming SDRs or SJBs during 120 minutes of
      intense cycling results in similar subsequent TT performances and are equally
      effective in maintaining blood glucose levels during exercise. Therefore, SDRs
      are a natural, pleasant, cost-effective CHO alternative to commercial SJBs that
      can be used during moderate- to high-intensity endurance exercise.

PMID- 21881534
TI  - Short-term effects of resistance training frequency on body composition and
      strength in middle-aged women.
AB  - Although a dose-response relationship between resistance training frequency and
      strength has been identified, there is limited research regarding the association
      between frequency and body composition. This study evaluated the effects of 3 vs.
      4 d.wk(-1) of resistance training on body composition and strength in middle-aged
      women. Twenty-one untrained women (age 47.6 +/- 1.2 years) completed 8 weeks of
      resistance training either 3 nonconsecutive days of the week using a traditional
      total-body protocol (RT3) or 4 consecutive days of the week using an alternating
      split-training protocol (RT4). The RT3 completed 3 sets of 8 exercises, whereas
      RT4 completed 3 sets of 6 upper body exercises or 6 sets of 3 lower body
      exercises. Both groups completed 72 sets per week of 8-12 repetitions at 50-80% 1
      repetition maximum. Weekly training volume load was calculated as the total
      number of repetitions * load (kg) completed per week. Body composition was
      measured using air displacement plethysmography. At baseline and after 8 weeks of
      resistance training, there were no significant between-group differences. Both
      protocols resulted in significant increases in absolute lean mass (1.1 +/- 0.3
      kg; p = 0.001), body weight (1.02 +/- 0.3 kg; p = 0.005), body mass index (0.3 +/
      0.1 kg.m(-2); p = 0.006), strength (p < 0.001), and weekly training volume load
      (p < 0.001). Correlation analysis revealed that weekly training volume load was
      strongly and positively related to gains in lean mass (r = 0.56, p = 0.05) and
      strength (r = 0.60, p = 0.006). In these untrained, middle-aged women, initial
      short-term gains in lean mass and strength were not influenced by training
      frequency when the number of training sets per week was equated.

PMID- 21881535
TI  - Overcoming blocks in apoptosis with BH3-mimetic therapy in haematological
      malignancies.
AB  - Blocks in apoptosis are now widely regarded as key pathophysiological
      maladaptations critical for tumour persistence. Importantly, it has also been
      recognised that they confer resistance to cytotoxic therapy, and hence often
      portend an adverse prognosis. The advent of BH3-mimetics represents a nascent
      clinical capability to directly reverse the evasion of apoptosis, and indeed
      exploit the very molecular abnormalities which have hitherto posed major
      obstacles to therapeutic success. Clinical trials with BH3-mimetics have
      demonstrated clear single agent anti-tumour activity in selected haematological
      malignancies. These drugs also offer promise as adjuncts to existing or emerging
      therapies in a broader range of cancers.

PMID- 21881536
TI  - Molecular methods in diagnosis and monitoring of haematological malignancies.
AB  - The use of the polymerase chain reaction (PCR) was a revolutionary step in
      molecular biology, allowing for small amounts of genetic material to be amplified
      and studied. The advent of real-time PCR was a further refinement that led to
      reliable quantification of RNA and DNA. This allowed response monitoring and the
      detection of minimal residual disease, which proved to have important
      correlations with outcome in certain malignancies. The technology is
      indispensable for physicians and pathologists caring for oncology patients. In
      this article we will review the applications of molecular technology in the
      diagnosis and management of malignancies. Using chronic myeloid leukaemia (CML)
      as an example, technical aspects and clinical correlations will be discussed,
      with emphasis on the importance of quality assurance and standardisation to allow
      for comparability of results across laboratories. We will also examine emerging
      technologies that allow for high throughput and rapid turnaround of specimens and
      speculate how these would affect outcomes in future health care. The established
      and emerging molecular technologies have applications in many fields of oncology.

PMID- 21881537
TI  - Polychromatic flow cytometry in the clinical laboratory.
AB  - Technological advances in flow cytometry include increasingly sophisticated
      instruments and an expanding range of fluorochromes. These advances are making it
      possible to detect an increasing number of markers on a single cell. The term
      polychromatic flow cytometry applies to such systems that detect five or more
      markers simultaneously. This review provides an overview of the current and
      future impact of polychromatic flow cytometry in the clinical laboratory. The use
      of multiple markers has several advantages in the diagnosis and monitoring of
      haematological malignancies. Cell populations can be analysed more
      comprehensively and efficiently, and abnormal populations can be distinguished
      more readily when normal counterparts are present. Polychromatic flow cytometry
      is particularly useful in the evaluation of plasma cells, and the role of flow
      cytometry in the assessment of plasma cell disorders is reviewed in depth. There
      is improved sensitivity in the assessment of small populations, which is critical
      in the evaluation of minimal residual disease. Flow cytometry can also play a
      role in assessment of circulating tumour cells in carcinoma. Introduction of
      polychromatic flow cytometry is a complex process with many challenges including
      design of antibody panels and instrument compensation. Developments in data
      analysis are required to realise the full benefits of the other technical
      advances. Standardisation of protocols may reduce inter-laboratory variation.
      While the complexity of polychromatic flow cytometry creates challenges, it has
      substantial potential to improve clinical analysis.

PMID- 21881538
TI  - The epigenomics revolution in myelodysplasia: a clinico-pathological perspective.
AB  - Rapid advances in molecular technologies are continually re-shaping the way we
      view and understand the mechanisms driving oncogenesis. The last decade has
      witnessed unparalleled change in the biology and therapy of the myelodysplastic
      syndromes (MDS), a heterogeneous collection of clonal myeloid disorders
      characterised by ineffective haematopoiesis and susceptibility to acute leukaemia
      transformation. Pivotal studies demonstrating the positive effects of
      hypomethylating agents on clinical outcome have brought an 'epigenomics
      revolution' to this disease, emphasising the importance of epigenetic mechanisms
      to the underlying pathogenesis of MDS. One of the most important future
      challenges in the MDS field will be to determine whether epigenetic therapies can
      be made more 'targeted' through identification of biomarkers which define subsets
      of patients most likely to benefit from treatment. A wave of novel mutations have
      recently been reported in MDS and other myeloid disorders, several of which
      regulate endogenous methylation networks within cells (including TET2, DNMT3A,
      IDH and EZH2). The relevance of these lesions in being able to predict response
      to epigenetic modulators and their correlation with epigenetic signatures in MDS
      are beginning to emerge.

PMID- 21881539
TI  - Ramipril modulates circadian gene expression in skeletal muscle.
AB  - OBJECTIVES: Treatment with angiotensin converting enzyme (ACE)-inhibitors
      favorably affects glucose metabolism and the development of diabetes mellitus by
      largely elusive mechanisms. To identify these mechanisms, we studied the effect
      of ACE-inhibition on gene expression in skeletal muscle, a primary target tissue
      for insulin in glucose homeostasis. METHODS: A subject-blinded and analyst
      blinded, placebo-controlled study was conducted in nine healthy men. Two
      consecutive muscle biopsies were conducted before and 9 h after a single dose of
      either 10-mg ramipril (n=6) or placebo (n=3), (randomly allocated). Muscle
      ribonucleic acid was subjected to transcriptome profiling. RESULTS: In both
      ramipril-treated or placebo-treated individuals, the majority of genes with
      differential expression between the two time points belonged to the family of
      diurnally regulated genes, such as the NR1D1 and NR1D2 genes (nuclear receptor
      subfamily 1, group D, members 1 and 2) or members of the period homolog family
      (PER1-3). Ramipril significantly modulated the expression of other diurnally
      regulated genes, such as aryl hydrocarbon receptor nuclear translocator-like
      (ARNTL), encoding aryl hydrocarbon receptor nuclear translocator-like, a core
      component of the circadian clock (P=0.02). Concomitant attenuation of NR1D1
      downregulation (-2.4-fold compared with -4.1-fold in placebo; P=0.04), a
      transcriptional repressor of ARNTL, supported the view that ramipril might
      modulate glucose homeostasis pathways involving the NR1D1 ARNTL axis. CONCLUSION:
      As circadian rhythms are deranged in patients who are diabetic, modulated
      expression of circadian clock genes by ramipril could explain the favorable
      metabolic effects of therapeutic ACE-inhibition.

PMID- 21881540
TI  - Beta2-adrenergic receptor polymorphisms as a determinant of preferential
      bronchodilator responses to beta2-agonist and anticholinergic agents in Japanese
      patients with chronic obstructive pulmonary disease.
AB  - BACKGROUND: Previous studies have shown that polymorphisms in the beta2
      adrenergic receptor gene (ADRB2) may influence bronchodilator response (BDR) to
      both beta2-agonists and anticholinergics, possibly by intracellular cross-talk,
      but in opposite ways, in the Japanese population. We hypothesized that the
      preferential response to either class of bronchodilators might be determined by
      ADRB2 polymorphisms in patients with chronic obstructive pulmonary disease
      (COPD). OBJECTIVE: To examine the association of ADRB2 polymorphisms and
      preferential BDR to beta2-agonists and anticholinergics in patients with COPD.
      DESIGN AND PARTICIPANTS: The participants had been enrolled in the Hokkaido COPD
      cohort study. BDR to either class of bronchodilators (salbutamol or oxytropium,
      0.4 mg) was measured every 6 months for 2 years. Considering the variation of BDR
      within and between days, mean values of postbronchodilator increases in forced
      expiratory volume in 1 s (DeltaFEV1) for the two agents measured at two different
      visits were initially used for the primary analysis (N=189). To confirm the
      results of the primary analysis, DeltaFEV1 measured at a single visit was also
      used for secondary analyses. RESULTS: Although a significant correlation between
      BDRs to salbutamol and to oxytropium was observed (P<0.001, r=0.36), there were
      individuals who responded preferentially to one of the two agents. When the
      participants were classified into two groups based on the bronchodilator causing
      the better response (salbutamol-dominant group and oxytropium-dominant group),
      Arg allele was significantly more common in the oxytropium-dominant group than in
      the salbutamol-dominant group (0.001<P<0.05). CONCLUSION: ADRB2 polymorphism may
      be a determinant of preferential BDR to either beta2-agonists or anticholinergics
      in patients with COPD.

PMID- 21881541
TI  - Transcriptional diversity at the UGT2B7 locus is dictated by extensive pre-mRNA
      splicing mechanisms that give rise to multiple mRNA splice variants.
AB  - OBJECTIVE: UGT2B7 is a key member of the UDP-glucuronosyltransferase (UGT) family
      that participates in glucuronidation of endogenous compounds and pharmaceuticals.
      Much evidence suggests a large interindividual variability of UGT2B7-mediated
      glucuronidation, which is still unexplained by polymorphisms. We hypothesized
      that alternative splicing may be responsible for the variability in the UGT2B7
      function. METHODS: We carried out a comprehensive scan for additional exons at
      this locus and discovered multiple alternative splicing events. We then
      determined transcript expression profiles across a large variety of human tissues
      and assessed some of these variants for their glucuronidation activity in human
      cells. RESULTS: In-depth analysis of the UGT2B7 gene structure led to the
      discovery of six novel exons. Kidney and liver samples presented the greatest
      enrichment of tissue-specific splicing, with 21 new UGT2B7 transcripts isolated.
      Furthermore, transcription from the proximal promoter (exon 1), associated with
      the active UGT2B7 mRNA isoform 1 (UGT2B7_v1), is most commonly observed in the
      gastrointestinal tract, whereas a distal promoter (exon 1a) induces the exclusion
      of the canonical exon 1 and is active in hormone-related tissues. We also showed
      that novel transcripts with alternative 3' ends could be translated into proteins
      lacking glucuronosyltransferase activity in human cells but acting as negative
      regulators on transferase activity when coexpressed with the active UGT2B7
      protein. CONCLUSION: Our findings point toward a significant variability in
      structure, abundance, and tissue-specific UGT2B7 transcriptome, in addition to
      novel functions for UGT2B7-derived proteins, all of which may ensure the
      production of tissue-specific proteomes and functions.

PMID- 21881543
TI  - Acute toxicity and hepatotoxicokinetic studies of Tamarindus indica extract.
AB  - Tamarindus indica is widely used as a food and beverage and in traditional
      medicine. The apparent lack of dose standardization in herbal medicine
      necessitates the evaluation of the lethality T. indica on Artemia salina nauplii
      and chicken embryos via in vitro and in vivo techniques. Furthermore,
      hepatotoxicokinetics of the crude extract and fractions on Wister rats was also
      assessed. At concentrations of 200, 20 and 2 ug/mL, crude extract and fractions
      showed brine shrimp death percentages ranging from 86.70% to 3.30% and the sub
      fractions showed death percentage ranges of 46.70% to 3.30%. Calculated LD50
      values ranged from 832 ug/mL to 5,019 ug/mL. Dosing Wister rats with 25% and 50%
      concentration of LD50 determined for crude extract and fractions on chicken
      embryos showed an elevation in the ALT and AST levels in the serum. Brine shrimps
      and chicken embryos showed a positive correlation, with R2 values of 0.541 and
      0.588 (P <= 0.05) for fractions and subfractions, respectively, as media for the
      lethality assay. Dose standardization in folk herbal medicine is imperative as T.
      indica used as food and medicine has been shown to be toxic at high doses. Brine
      shrimp and chicken embryos may be comparably used as medium for toxicity assay.

PMID- 21881542
TI  - DCDC2 genetic variants and susceptibility to developmental dyslexia.
AB  - OBJECTIVE(S): Developmental dyslexia is a heritable condition, with genetic
      factors accounting for 44-75% of the variance in performance tests of reading
      component subphenotypes. Compelling genetic linkage and association evidence
      supports a quantitative trait locus in the 6p21.3 region that encodes a gene
      called DCDC2. In this study, we explored the contribution of two DCDC2 markers to
      dyslexia, related reading and memory phenotypes in nuclear families of Italian
      origin. METHODS: The 303 nuclear families recruited on the basis of having a
      proband with developmental dyslexia have been studied with 6p21.3 markers,
      BV677278 and rs793862. Marker-trait association was investigated by the
      quantitative transmission disequilibrium test (version 2.5.1) that allows for the
      analyses of quantitative traits. Seven phenotypes were used in association
      analyses, that is, word and nonword reading, word and nonword spelling,
      orthographic choice, memory, and the affected status based on inclusion criteria.
      RESULTS: Quantitative transmission disequilibrium test analyses yielded evidence
      for association between reading skills and the BV677278 deletion (empirical P
      values=0.025-0.029) and between memory and BV677278 allele 10 (empirical P
      value=0.0001). CONCLUSION: Our result adds further evidence in support of DCDC2
      contributing to the deficits in developmental dyslexia. More specifically, our
      data support the view that DCDC2 influences both reading and memory impairments
      thus shedding further light into the etiologic basis and the phenotypic
      complexity of developmental dyslexia.

PMID- 21881544
TI  - Oral cancer trends in a single head-and-neck cancer center in the  Netherlands;
      decline in T-stage at the time of admission.
AB  - OBJECTIVES: In this study we evaluated the possible epidemiologic changes of oral
      cancer patients in the Netherlands between the years 1980-1984 and 2000-2004. We
      specifically studied the differences in male-female ratio, age, TNM-stage, site
      distribution, and alcohol and tobacco use. MATERIALS AND METHODS: Patients from
      the VU University Medical Center with an oral squamous cell carcinoma of the oral
      cavity registered in 1980-1984 (n=200), group 1, were compared to patients
      registered in 2000-2004 (n=184), group 2. Trends in prevalence, site
      distribution, TNM-stage, alcohol and tobacco use, age and gender were studied.
      RESULTS: The male-female ratio has decreased from 1.8 to 1.2. There were no
      differences in age between the two groups of patients. The site distribution was
      similar in both groups. The most commonly involved sites were the tongue and the
      floor of mouth. In group 2 more patients were diagnosed with a T1 tumour. There
      were no differences in tobacco use between the two different groups. There were
      much more light drinkers (0-2 drinks per day) in group 2 than in group 1, whereas
      there were more heavy drinkers (>4 per day) in group 1 than in group 2 (p<0.001).
      This was observed in both male and female patients. CONCLUSION: In our study
      there were no significant differences between the patients registered in the
      years 1980-1984 and 2000-2004 regarding the mean age of the patients, site
      distribution and smoking habits. The male-female ratio has decreased. In the
      recent group more patients were staged T1N0 and there was a strong decrease of
      the patients who were heavy drinkers.

PMID- 21881545
TI  - Office-related antibiotic prescribing for persons aged <= 14 years--United
      States, 1993-1994 to 2007-2008.
AB  - In 2003, the Institute of Medicine identified antibiotic resistance as a key
      microbial threat to health in the United States and recommended promoting
      appropriate antibiotic use as an important strategy to address this threat.
      Antibiotic use contributes to development of antibiotic resistance on both the
      individual and country level. To examine trends in pediatric antibiotic
      prescribing in physician offices, CDC analyzed data from the National Ambulatory
      Medical Care Survey (NAMCS) for the period 1993-1994 to 2007-2008. This report
      summarizes the results of that analysis, which found that antibiotic prescribing
      rates for persons aged <= 14 years who had visited physician offices decreased
      24% from 300 antibiotic courses per 1,000 office visits in 1993-1994 to 229
      antibiotic courses per 1,000 office visits in 2007-2008. Among the five acute
      respiratory infections (ARIs) examined, antibiotic prescribing rates decreased
      26% for pharyngitis and 19% for nonspecific upper respiratory infection (common
      cold); prescribing rates for otitis media, bronchitis, and sinusitis did not
      change significantly. Although the overall antibiotic prescribing rate for
      persons aged <= 14 years has decreased, the rate remains inappropriately high.
      Further efforts are needed to decrease inappropriate antibiotic prescribing for
      persons aged <= 14 years.

PMID- 21881546
TI  - National and state vaccination coverage among children aged 19-35 months--United
      States, 2010.
AB  - The National Immunization Survey (NIS) monitors vaccination coverage among
      children aged 19-35 months using a random-digit-dialed sample of telephone
      numbers of households to evaluate childhood immunization programs in the United
      States. This report describes the 2010 NIS coverage estimates for children born
      during January 2007-July 2009. Nationally, vaccination coverage increased in 2010
      compared with 2009 for >= 1 dose of measles, mumps, and rubella vaccine (MMR),
      from 90.0% to 91.5%; >= 4 doses of pneumococcal conjugate vaccine (PCV), from
      80.4% to 83.3%; the birth dose of hepatitis B vaccine (HepB), from 60.8% to
      64.1%; >= 2 doses of hepatitis A vaccine (HepA), from 46.6% to 49.7%; rotavirus
      vaccine, from 43.9% to 59.2%; and the full series of Haemophilus influenzae type
      b (Hib) vaccine, from 54.8% to 66.8%. Coverage for poliovirus vaccine (93.3%),
      MMR (91.5%), >= 3 doses HepB (91.8%), and varicella vaccine (90.4%) continued to
      be at or above the national health objective targets of 90% for these vaccines.*
      The percentage of children who had not received any vaccinations remained low
      (<1%). For most vaccines, no disparities by racial/ethnic group were observed,
      with coverage for other racial/ethnic groups in 2010 similar to or higher than
      coverage among white children. However, disparities by poverty status still
      exist. Maintaining high vaccination coverage levels is important to reduce the
      burden of vaccine-preventable diseases and prevent a resurgence of these diseases
      in the United States, particularly in undervaccinated populations.

PMID- 21881547
TI  - Human rabies--Wisconsin, 2010.
AB  - In late December 2010, a male resident of Wisconsin, aged 70 years, sought
      treatment for progressive right shoulder pain, tremors, abnormal behavior, and
      dysphagia at an emergency department (ED). He was admitted for observation and
      treated with benzodiazepines and haloperidol, a neuroleptic, for presumed alcohol
      withdrawal syndrome. The next day, he had rhabdomyolysis, fever, and rigidity,
      and neuroleptic malignant syndrome was diagnosed. The neuroleptic was
      discontinued, but the patient's clinical status worsened, with encephalopathy,
      respiratory failure, acute renal failure requiring hemodialysis, and episodes of
      cardiac arrest. With continued clinical deterioration, additional causes were
      considered, including rabies. On hospital day 12, rabies virus antigens and
      nucleic acid were detected in the nuchal skin biopsy and rabies virus nucleic
      acid in saliva specimens sent to CDC. A rabies virus variant associated with
      silver-haired bats (Lasionycteris noctivagans) was identified. The patient died
      on hospital day 13. His spouse reported that they had been selling firewood, and
      bats had been present in the woodpile; however, the man had not reported a bat
      bite. Two relatives and five health-care workers potentially exposed to the man's
      saliva received postexposure prophylaxis. This case highlights the variable
      presentations of rabies and the ease with which a diagnosis of rabies can be
      missed in a clinically challenging patient with comorbidities. Clinicians should
      consider rabies in the differential diagnosis for patients with progressive
      encephalitis or neurologic illness of unknown etiology and caregivers should take
      precautions to avoid exposure to body fluids. Continued public education
      regarding risks for rabies virus exposure during interactions with wildlife,
      particularly bats, is important.

PMID- 21881548
TI  - Trends in in-hospital newborn male circumcision--United States, 1999-2010.
AB  - The publication of three recent studies showing that circumcision of adult,
      African, heterosexual men reduces their risk for acquiring human immunodeficiency
      virus infection and other sexually transmitted infections has stimulated interest
      in the practice of routine newborn male circumcision (NMC) and the benefits it
      might confer for HIV prevention. In the United States, rates of in-hospital NMC
      increased from 48.3% during 1988-1991 to 61.1% during 1997-2000. To monitor
      trends in in-hospital NMC during 1999-2010, CDC used three independent data
      sources (the National Hospital Discharge Survey [NHDS] from the National Center
      for Health Statistics, the Nationwide Inpatient Sample [NIS] from the Agency for
      Healthcare Research and Quality, and the Charge Data Master [CDM] from SDIHealth)
      to estimate rates of NMC. Each system collects discharge data on inpatient
      hospitalization.

PMID- 21881549
TI  - Notes from the field: Measles outbreak--Indiana, June-July 2011.
AB  - On June 20, 2011, an emergency department (ED) physician reported five
      epidemiologically linked measles cases to the Indiana State Department of Health.
      The subsequent investigation identified a total of 14 confirmed cases in
      northeast Indiana. Of these, 10 were laboratory-confirmed, and four were among
      household contacts of persons with laboratory-confirmed measles. Of the 14
      patients, 13 were unvaccinated persons in the same extended family. The nonfamily
      member was a child aged 23 months who had received 1 dose of measles, mumps, and
      rubella vaccine 4 months before illness onset. Four of the 14 patients were
      males; median age was 11.5 years (range: 15 months-27 years). One patient was a
      woman in week 32 of pregnancy who was hospitalized for acute pneumonitis.

PMID- 21881550
TI  - Mental illness surveillance among adults in the United States.
AB  - Mental illnesses account for a larger proportion of disability in developed
      countries than any other group of illnesses, including cancer and heart disease.
      In 2004, an estimated 25% of adults in the United States reported having a mental
      illness in the previous year. The economic cost of mental illness in the United
      States is substantial, approximately $300 billion in 2002. Population surveys and
      surveys of health-care use measure the occurrence of mental illness, associated
      risk behaviors (e.g., alcohol and drug abuse) and chronic conditions, and use of
      mental health-related care and clinical services. Population-based surveys and
      surveillance systems provide much of the evidence needed to guide effective
      mental health promotion, mental illness prevention, and treatment programs. This
      report summarizes data from selected CDC surveillance systems that measure the
      prevalence and impact of mental illness in the U.S. adult population. CDC
      surveillance systems provide several types of mental health information:
      estimates of the prevalence of diagnosed mental illness from self-report or
      recorded diagnosis, estimates of the prevalence of symptoms associated with
      mental illness, and estimates of the impact of mental illness on health and well
      being. Data from the CDC 2005-2008 National Health and Nutrition Examination
      Survey indicate that 6.8% of adults had moderate to severe depression in the 2
      weeks before completing the survey. State-specific data from the CDC 2006
      Behavioral Risk Factor Surveillance System (BRFSS), the most recent BRFSS data
      available, indicate that the prevalence of moderate to severe depression was
      generally higher in southeastern states compared with other states. Two other CDC
      surveys on ambulatory care services, the National Ambulatory Medical Care Survey
      and the National Hospital Ambulatory Medical Care Survey, indicate that during
      2007-2008, approximately 5% of ambulatory care visits involved patients with a
      diagnosis of a mental health disorder, and most of these were classified as
      depression, psychoses, or anxiety disorders. Future surveillance should pay
      particular attention to changes in the prevalence of depression both nationwide
      and at the state and county levels. In addition, national and state-level mental
      illness surveillance should measure a wider range of psychiatric conditions and
      should include anxiety disorders. Many mental illnesses can be managed
      successfully, and increasing access to and use of mental health treatment
      services could substantially reduce the associated morbidity.

PMID- 21881551
TI  - Clinical and behavioral characteristics of adults receiving medical care for HIV
      infection --- Medical Monitoring Project, United States, 2007.
AB  - PROBLEM: As of December 31, 2008, an estimated 663,084 persons were living with a
      diagnosis of human immunodeficiency virus (HIV) infection in the 40 U.S. states
      that have had confidential name-based HIV infection reporting since at least
      January 2006. Although HIV surveillance programs in the United States collect
      information about persons who have received a diagnosis of HIV infection and
      acquired immunodeficiency syndrome (AIDS), supplemental surveillance projects are
      needed to collect information about care-seeking behaviors, health-care use, and
      other behaviors among persons living with HIV. Data on the clinical and
      behavioral characteristics of persons receiving medical care for HIV infection
      are critical to reduce HIV-related morbidity and mortality and for program
      planning to allocate services and resources, guide prevention planning, assess
      unmet medical and ancillary service needs, and help develop intervention programs
      and health policies at the local, state, and national levels. REPORTING PERIOD
      COVERED: Data were collected during June 2007-September 2008 for patients who
      received medical care in 2007 (sampled from January 1-April 30). DESCRIPTION OF
      THE SYSTEM: The Medical Monitoring Project (MMP) is an ongoing, multisite
      supplemental surveillance project that assesses behaviors, clinical
      characteristics, and quality of care of HIV-infected persons who are receiving
      medical care. Participants must be aged >= 18 years and have received medical
      care at sampled facilities that provide HIV medical care within participating MMP
      project areas. Self-reported behavioral and selected clinical data are collected
      using an in-person interview. A total of 26 project areas in 19 states and Puerto
      Rico were funded to collect data during the 2007 MMP data collection cycle.
      RESULTS: The results from the 2007 MMP cycle indicated that among 3,643
      participants, a total of 3,040 (84%) had some form of health insurance or
      coverage during the 12 months before the interview; of these, 45% reported having
      Medicaid, 37% reported having private health insurance or coverage through a
      health maintenance organization, and 30% reported having Medicare. A total of
      3,091 (85%) of the participants were currently taking antiretroviral medications.
      Among 3,609 participants who reported ever having a CD4 T-lymphocyte test, 2,996
      (83%) reported having three or more CD4 T-lymphocyte tests in the 12 months
      before the interview. Among 3,567 participants who reported ever having an HIV
      viral load test, 2,946 (83%) reported having three or more HIV viral load tests
      in the 12 months before the interview. Among 3,643 participants, 45% needed HIV
      case management, 33% needed mental health counseling, and 32% needed assistance
      finding dental services during the 12 months before the interview; 8%, 13%, and
      25% of these participants who needed the services, respectively, had not received
      these services by the time of the interview. Noninjection drugs were used for
      nonmedical purposes by 1,117 (31%) participants during the 12 months before the
      interview, and 122 (3%) participants had used injection drugs for nonmedical
      purposes. Unprotected anal intercourse was reported by 527 (54%) of 970 men who
      reported having anal sex with a man during the 12 months before the interview.
      Unprotected anal or vaginal intercourse was reported by 176 (32%) of the 553 men
      who reported having anal or vaginal intercourse with a woman during the 12 months
      before the interview. Unprotected anal or vaginal intercourse was reported by 216
      (42%) of the 516 women who reported having anal or vaginal intercourse with a man
      during the 12 months before the interview. INTERPRETATION: The findings in this
      report indicate that in 2007, most persons with HIV infection who were receiving
      medical care were taking antiretroviral therapy and had some form of health
      insurance or coverage; however, some persons were not receiving needed critical
      ancillary services, such as HIV case management or help finding dental services.
      In addition, some persons living with HIV infection engaged in behaviors, such as
      unprotected sex, that increase the risk for transmitting HIV to sexual partners,
      and some used noninjection or injection drugs for nonmedical purposes, which
      might decrease adherence to antiretroviral therapy and increase health-risk
      behaviors. PUBLIC HEALTH ACTIONS: MMP data can be used to monitor the national
      HIV/AIDS strategy goal of increasing access to care and optimizing health
      outcomes among persons living with HIV. Persons infected with HIV who are not
      receiving needed ancillary services highlight missed opportunities for access to
      care and other supportive services, information that can be used to advocate for
      additional resources. Drug use among persons with HIV infection underscores the
      continued need for substance abuse treatment services for this population. In
      addition, prevention services and programs are needed to decrease the number of
      HIV-infected persons engaging in unprotected sex. The data in this report can be
      included in local, state, and national HIV/AIDS epidemiologic profiles and shared
      with community stakeholders. Although data from the 2007 MMP cycle might not be
      representative of all persons receiving medical care for HIV infection in the
      United States or in the individual project areas, future MMP cycles are expected
      to yield weighted national estimates representing all HIV-infected persons
      receiving medical care in the United States.

PMID- 21881552
TI  - A portable fiberoptic ratiometric fluorescence analyzer provides rapid point-of
      care determination of glomerular filtration rate in large animals.
AB  - Measurement of the glomerular filtration rate (GFR) is the gold standard for
      precise assessment of kidney function. A rapid, point-of-care determination of
      the GFR may provide advantages in the clinical setting over currently available
      assays. Here we demonstrate a proof of principle for such an approach in a pig
      and dogs, two species that approximate the vascular access and GFR results
      expected in humans. In both animal models, a sub-millimeter optical fiber that
      delivered excitation light and collected fluorescent emissions was inserted into
      a peripheral vein (dog) or central venous access (pig) by means of commercial
      intravenous catheters. A mixture of fluorescent chimeras of a small freely
      filterable reporter and large non-filterable plasma volume marker were infused as
      a bolus, excited by light-emitting diodes, and the in vivo signals detected and
      quantified by photomultiplier tubes in both species in less than 60 min.
      Concurrent standardized 6-h iohexol plasma kidney clearances validated the
      accuracy of our results for both physiologic and a chronic kidney disease
      setting. Thus, our ratiometric technique allows for both measurement of plasma
      vascular volume and highly accurate real-time GFR determinations, enabling
      clinical decision making in real time.

PMID- 21881553
TI  - Dietary acid reduction with fruits and vegetables or bicarbonate attenuates
      kidney injury in patients with a moderately reduced glomerular filtration rate
      due to hypertensive nephropathy.
AB  - The neutralization of dietary acid with sodium bicarbonate decreases kidney
      injury and slows the decline of the glomerular filtration rate (GFR) in animals
      and patients with chronic kidney disease. The sodium intake, however, could be
      problematic in patients with reduced GFR. As alkali-induced dietary protein
      decreased kidney injury in animals, we compared the efficacy of alkali-inducing
      fruits and vegetables with oral sodium bicarbonate to diminish kidney injury in
      patients with hypertensive nephropathy at stage 1 or 2 estimated GFR. All
      patients were evaluated 30 days after no intervention; daily oral sodium
      bicarbonate; or fruits and vegetables in amounts calculated to reduce dietary
      acid by half. All patients had 6 months of antihypertensive control by
      angiotensin-converting enzyme inhibition before and during these studies, and
      otherwise ate ad lib. Indices of kidney injury were not changed in the stage 1
      group. By contrast, each treatment of stage 2 patients decreased urinary albumin,
      N-acetyl beta-D-glucosaminidase, and transforming growth factor beta from the
      controls to a similar extent. Thus, a reduction in dietary acid decreased kidney
      injury in patients with moderately reduced eGFR due to hypertensive nephropathy
      and that with fruits and vegetables was comparable to sodium bicarbonate. Fruits
      and vegetables appear to be an effective kidney protective adjunct to blood
      pressure reduction and angiotensin-converting enzyme inhibition in hypertensive
      and possibly other nephropathies.

PMID- 21881554
TI  - Progressive histological damage in renal allografts is associated with expression
      of innate and adaptive immunity genes.
AB  - The degree of progressive chronic histological damage is associated with long
      term renal allograft survival. In order to identify promising molecular targets
      for timely intervention, we examined renal allograft protocol and indication
      biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome
      microarray expression profiling. In data-driven analysis, we found a highly
      regulated pattern of adaptive and innate immune gene expression that correlated
      with established or ongoing histological chronic injury, and also with
      development of future chronic histological damage, even in histologically
      pristine kidneys. Hence, histologically unrecognized immunological injury at a
      molecular level sets the stage for the development of chronic tissue injury,
      while the same molecular response is accentuated during established and worsening
      chronic allograft damage. Irrespective of the hypothesized immune or nonimmune
      trigger for chronic allograft injury, a highly orchestrated regulation of innate
      and adaptive immune responses was found in the graft at the molecular level. This
      occurred months before histologic lesions appear, and quantitatively below the
      diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus,
      measurement of specific immune gene expression in protocol biopsies may be
      warranted to predict the development of subsequent chronic injury in
      histologically quiescent grafts and as a means to titrate immunosuppressive
      therapy.

PMID- 21881555
TI  - Complement factor H variants I890 and L1007 while commonly associated with
      atypical hemolytic uremic syndrome are polymorphisms with no functional
      significance.
AB  - Mutations and polymorphisms in the gene-encoding factor H (CFH) are associated
      with atypical hemolytic uremic syndrome, dense deposit disease, and age-related
      macular degeneration. Many of these CFH genetic variations disrupt the regulatory
      role of factor H, supporting the concept that dysregulation of complement is a
      unifying pathogenic feature of these disorders. Evidence of a causal relationship
      with the disease is, however, not available for all CFH genetic variations found
      in patients, which is a potential cause of misinterpretations with important
      consequences for the patients and their relatives. CFH I890 and L1007 are two
      genetic variations repeatedly associated with atypical hemolytic uremic syndrome
      and also found in patients with dense deposit disease and age-related macular
      degeneration. Here we report an extensive genetic and functional analysis of
      these CFH variants. Our results indicate that I890 and L1007 segregate together
      as part of a distinct and relatively infrequent CFH haplotype in Caucasians.
      Extensive analysis of the S890/V1007 (control) and I890/L1007 (disease
      associated) factor H protein variants failed to provide evidence that these amino
      acid changes have functional implications. Thus, the presence of the I890 and
      L1007 variants in healthy individuals and their high frequency in sub-Saharan
      African and African-American populations strongly suggest that I890 and L1007 are
      rare factor H polymorphisms unrelated to disease.

PMID- 21881556
TI  - Pleiotrophin triggers inflammation and increased peritoneal permeability leading
      to peritoneal fibrosis.
AB  - Long-term peritoneal dialysis induces peritoneal fibrosis with submesothelial
      fibrotic tissue. Although angiogenesis and inflammatory mediators are involved in
      peritoneal fibrosis, precise molecular mechanisms are undefined. To study this,
      we used microarray analysis and compared gene expression profiles of the
      peritoneum in control and chlorhexidine gluconate (CG)-induced peritoneal
      fibrosis mice. One of the 43 highly upregulated genes was pleiotrophin, a midkine
      family member, the expression of which was also upregulated by the solution used
      to treat mice by peritoneal dialysis. This growth factor was found in fibroblasts
      and mesothelial cells within the underlying submesothelial compact zones of mice,
      and in human peritoneal biopsy samples and peritoneal dialysate effluent.
      Recombinant pleiotrophin stimulated mitogenesis and migration of mouse
      mesothelial cells in culture. We found that in wild-type mice, CG treatment
      increased peritoneal permeability (measured by equilibration), increased mRNA
      expression of TGF-beta1, connective tissue growth factor and fibronectin, TNF
      alpha and IL-1beta expression, and resulted in infiltration of CD3-positive T
      cells, and caused a high number of Ki-67-positive proliferating cells. All of
      these parameters were decreased in peritoneal tissues of CG-treated pleiotrophin
      knockout mice. Thus, an upregulation of pleiotrophin appears to play a role in
      fibrosis and inflammation during peritoneal injury.

PMID- 21881557
TI  - Exosomes and the kidney: prospects for diagnosis and therapy of renal diseases.
AB  - Exosomes are 40-100 nm membrane vesicles secreted into the extracellular space by
      numerous cell types. These structures can be isolated from body fluids including
      urine and plasma. Exosomes contain proteins, mRNAs, miRNAs, and signaling
      molecules that reflect the physiological state of their cells of origin and
      consequently provide a rich source of potential biomarker molecules. Aside from
      diagnostic uses, exosome-mediated transfer of proteins, mRNAs, miRNAs, and
      signaling molecules offer the promise that they may be used for therapeutic
      purposes. In this review, we integrate new knowledge about exosomes from outside
      the field of nephrology with recent progress by renal researchers in order to
      provide a basis for speculation about how the study of exosomes may affect the
      fields of nephrology and renal physiology in the next few years.

PMID- 21881560
TI  - A close nuclear black-hole pair in the spiral galaxy NGC 3393.
AB  - The current picture of galaxy evolution advocates co-evolution of galaxies and
      their nuclear massive black holes, through accretion and galactic merging. Pairs
      of quasars, each with a massive black hole at the centre of its galaxy, have
      separations of 6,000 to 300,000 light years (refs 2 and 3; 1 parsec = 3.26 light
      years) and exemplify the first stages of this gravitational interaction. The
      final stages of the black-hole merging process, through binary black holes and
      final collapse into a single black hole with gravitational wave emission, are
      consistent with the sub-light-year separation inferred from the optical spectra
      and light-variability of two such quasars. The double active nuclei of a few
      nearby galaxies with disrupted morphology and intense star formation (such as NGC
      6240 with a separation of about 2,600 light years and Mrk 463 with a separation
      of about 13,000 light years between the nuclei) demonstrate the importance of
      major mergers of equal-mass spiral galaxies in this evolution; such mergers lead
      to an elliptical galaxy, as in the case of the double-radio-nucleus elliptical
      galaxy 0402+379 (with a separation of about 24 light years between the nuclei).
      Minor mergers of a spiral galaxy with a smaller companion should be a more common
      occurrence, evolving into spiral galaxies with active massive black-hole pairs,
      but have hitherto not been seen. Here we report the presence of two active
      massive black holes, separated by about 490 light years, in the Seyfert galaxy
      NGC 3393 (50 Mpc, about 160 million light years). The regular spiral morphology
      and predominantly old circum-nuclear stellar population of this galaxy, and the
      closeness of the black holes embedded in the bulge, provide a hitherto missing
      observational point to the study of galaxy/black hole evolution. Comparison of
      our observations with current theoretical models of mergers suggests that they
      are the result of minor merger evolution.

PMID- 21881558
TI  - Systems biology of kidney diseases.
AB  - Kidney diseases manifest in progressive loss of renal function, which ultimately
      leads to complete kidney failure. The mechanisms underlying the origins and
      progression of kidney diseases are not fully understood. Multiple factors
      involved in the pathogenesis of kidney diseases have made the traditional
      candidate gene approach of limited value toward full understanding of the
      molecular mechanisms of these diseases. A systems biology approach that
      integrates computational modeling with large-scale data gathering of the
      molecular changes could be useful in identifying the multiple interacting genes
      and their products that drive kidney diseases. Advances in biotechnology now make
      it possible to gather large data sets to characterize the role of the genome,
      epigenome, transcriptome, proteome, and metabolome in kidney diseases. When
      combined with computational analyses, these experimental approaches will provide
      a comprehensive understanding of the underlying biological processes. Multiscale
      analysis that connects the molecular interactions and cell biology of different
      kidney cells to renal physiology and pathology can be utilized to identify
      modules of biological and clinical importance that are perturbed in disease
      processes. This integration of experimental approaches and computational modeling
      is expected to generate new knowledge that can help to identify marker sets to
      guide the diagnosis, monitor disease progression, and identify new therapeutic
      targets.

PMID- 21881563
TI  - Optimizing revascularization strategies in coronary artery disease for optimal
      benefit to patients.
AB  - Coronary artery bypass grafting (CABG) and percutaneous coronary intervention
      (PCI) have undergone substantial technological advances, and revascularization is
      an established therapeutic option in the treatment of coronary artery disease
      (CAD). Here we focus on optimization of decision making in revascularization
      strategies, as is being addressed in recent large clinical trials and the
      guidelines issued by the European Society of Cardiology (ESC) and the European
      Association for Cardio-Thoracic Surgery (EACTS).

PMID- 21881559
TI  - Mirror extreme BMI phenotypes associated with gene dosage at the chromosome
      16p11.2 locus.
AB  - Both obesity and being underweight have been associated with increased mortality.
      Underweight, defined as a body mass index (BMI) <= 18.5 kg per m(2) in adults and
      <= -2 standard deviations from the mean in children, is the main sign of a series
      of heterogeneous clinical conditions including failure to thrive, feeding and
      eating disorder and/or anorexia nervosa. In contrast to obesity, few genetic
      variants underlying these clinical conditions have been reported. We previously
      showed that hemizygosity of a ~600-kilobase (kb) region on the short arm of
      chromosome 16 causes a highly penetrant form of obesity that is often associated
      with hyperphagia and intellectual disabilities. Here we show that the
      corresponding reciprocal duplication is associated with being underweight. We
      identified 138 duplication carriers (including 132 novel cases and 108 unrelated
      carriers) from individuals clinically referred for developmental or intellectual
      disabilities (DD/ID) or psychiatric disorders, or recruited from population-based
      cohorts. These carriers show significantly reduced postnatal weight and BMI. Half
      of the boys younger than five years are underweight with a probable diagnosis of
      failure to thrive, whereas adult duplication carriers have an 8.3-fold increased
      risk of being clinically underweight. We observe a trend towards increased
      severity in males, as well as a depletion of male carriers among non-medically
      ascertained cases. These features are associated with an unusually high frequency
      of selective and restrictive eating behaviours and a significant reduction in
      head circumference. Each of the observed phenotypes is the converse of one
      reported in carriers of deletions at this locus. The phenotypes correlate with
      changes in transcript levels for genes mapping within the duplication but not in
      flanking regions. The reciprocal impact of these 16p11.2 copy-number variants
      indicates that severe obesity and being underweight could have mirror
      aetiologies, possibly through contrasting effects on energy balance.

PMID- 21881562
TI  - The genome of the green anole lizard and a comparative analysis with birds and
      mammals.
AB  - The evolution of the amniotic egg was one of the great evolutionary innovations
      in the history of life, freeing vertebrates from an obligatory connection to
      water and thus permitting the conquest of terrestrial environments. Among
      amniotes, genome sequences are available for mammals and birds, but not for non
      avian reptiles. Here we report the genome sequence of the North American green
      anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes
      are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC
      and low repeat content that are characteristic of avian microchromosomes. Also,
      A. carolinensis mobile elements are very young and diverse-more so than in any
      other sequenced amniote genome. The GC content of this lizard genome is also
      unusual in its homogeneity, unlike the regionally variable GC content found in
      mammals and birds. We describe and assign sequence to the previously unknown A.
      carolinensis X chromosome. Comparative gene analysis shows that amniote egg
      proteins have evolved significantly more rapidly than other proteins. An anole
      phylogeny resolves basal branches to illuminate the history of their repeated
      adaptive radiations.

PMID- 21881564
TI  - Pharmacogenetics: call to action.

PMID- 21881565
TI  - Paraoxonase 1 (PON1) gene variants are not associated with clopidogrel response.
AB  - A common functional variant in paraoxonase 1 (PON1), Q192R, was recently reported
      to be a major determinant of clopidogrel response. This variant was genotyped in
      566 participants of the Amish Pharmacogenomics of Anti-Platelet Intervention
      (PAPI) study and in 227 percutaneous coronary intervention (PCI) patients. Serum
      paraoxonase activity was measured in a subset of 79 PAPI participants. PON1 Q192R
      was not associated with pre- or post-clopidogrel platelet aggregation in the PAPI
      study (P = 0.16 and P = 0.21, respectively) or the PCI cohort (P = 0.47 and P =
      0.91, respectively). The Q192 allele was not associated with cardiovascular
      events (hazard ratio (HR) 0.46, 95% confidence interval (CI) 0.20-1.06; P =
      0.07). No correlation was observed between paraoxonase activity and post
      clopidogrel platelet aggregation (r(2) < 0.01, P = 0.78). None of 49 additional
      PON1 variants evaluated was associated with post-clopidogrel platelet
      aggregation. These findings do not support a role for PON1 as a determinant of
      clopidogrel response.

PMID- 21881566
TI  - Specifying the neurobiological basis of human attachment: brain, hormones, and
      behavior in synchronous and intrusive mothers.
AB  - The mother-infant bond provides the foundation for the infant's future mental
      health and adaptation and depends on the provision of species-typical maternal
      behaviors that are supported by neuroendocrine and motivation-affective neural
      systems. Animal research has demonstrated that natural variations in patterns of
      maternal care chart discrete profiles of maternal brain-behavior relationships
      that uniquely shape the infant's lifetime capacities for stress regulation and
      social affiliation. Such patterns of maternal care are mediated by the
      neuropeptide Oxytocin and by stress- and reward-related neural systems. Human
      studies have similarly shown that maternal synchrony--the coordination of
      maternal behavior with infant signals--and intrusiveness--the excessive
      expression of maternal behavior--describe distinct and stable maternal styles
      that bear long-term consequences for infant well-being. To integrate brain,
      hormones, and behavior in the study of maternal-infant bonding, we examined the
      fMRI responses of synchronous vs intrusive mothers to dynamic, ecologically valid
      infant videos and their correlations with plasma Oxytocin. In all, 23 mothers
      were videotaped at home interacting with their infants and plasma OT assayed.
      Sessions were micro-coded for synchrony and intrusiveness. Mothers were scanned
      while observing several own and standard infant-related vignettes. Synchronous
      mothers showed greater activations in the left nucleus accumbens (NAcc) and
      intrusive mothers exhibited higher activations in the right amygdala. Functional
      connectivity analysis revealed that among synchronous mothers, left NAcc and
      right amygdala were functionally correlated with emotion modulation, theory-of
      mind, and empathy networks. Among intrusive mothers, left NAcc and right amygdala
      were functionally correlated with pro-action areas. Sorting points into
      neighborhood (SPIN) analysis demonstrated that in the synchronous group, left
      NAcc and right amygdala activations showed clearer organization across time,
      whereas among intrusive mothers, activations of these nuclei exhibited greater
      cross-time disorganization. Correlations between Oxytocin with left NAcc and
      right amygdala activations were found only in the synchronous group. Well-adapted
      parenting appears to be underlay by reward-related motivational mechanisms,
      temporal organization, and affiliation hormones, whereas anxious parenting is
      likely mediated by stress-related mechanisms and greater neural disorganization.
      Assessing the integration of motivation and social networks into unified neural
      activity that reflects variations in patterns of parental care may prove useful
      for the study of optimal vs high-risk parenting.

PMID- 21881561
TI  - Antibiotic resistance is ancient.
AB  - The discovery of antibiotics more than 70 years ago initiated a period of drug
      innovation and implementation in human and animal health and agriculture. These
      discoveries were tempered in all cases by the emergence of resistant microbes.
      This history has been interpreted to mean that antibiotic resistance in
      pathogenic bacteria is a modern phenomenon; this view is reinforced by the fact
      that collections of microbes that predate the antibiotic era are highly
      susceptible to antibiotics. Here we report targeted metagenomic analyses of
      rigorously authenticated ancient DNA from 30,000-year-old Beringian permafrost
      sediments and the identification of a highly diverse collection of genes encoding
      resistance to beta-lactam, tetracycline and glycopeptide antibiotics. Structure
      and function studies on the complete vancomycin resistance element VanA confirmed
      its similarity to modern variants. These results show conclusively that
      antibiotic resistance is a natural phenomenon that predates the modern selective
      pressure of clinical antibiotic use.

PMID- 21881567
TI  - Estradiol modulates effort-based decision making in female rats.
AB  - Disorders of the dopamine system, such as schizophrenia or stimulant addiction,
      are associated with impairments in different forms of cost/benefit decision
      making. The neural circuitry (ie amygdala, prefrontal cortex, nucleus accumbens)
      underlying these functions receives dopamine input, which is thought to have a
      central role in mediating cost/benefit decisions. Estradiol modulates dopamine
      activity, and estrogen receptors (ERs) are found within this neurocircuitry,
      suggesting that decision making may be influenced by estradiol. The present study
      examined the contribution of estradiol and selective ERalpha and beta agonists on
      cost/benefit decision making in adult female Long-Evans rats. An effort
      discounting task was utilized, where rats could either emit a single response on
      a low-reward lever to receive two pellets, or make 2, 5, 10, or 20 responses on a
      high-reward lever to obtain four pellets. Ovariectomy increased the choice on the
      high-reward lever, whereas replacement with high (10 MUg), but not low (0.3 MUg),
      levels of estradiol benzoate reduced the choice on the high-reward lever.
      Interestingly, both an ERalpha agonist (propyl-pyrazole triol (PPT)) and an
      ERbeta agonist (diarylpropionitrile (DPN)) increased choice on the high-reward
      lever when administered independently, but when these two agonists were combined,
      a decrease in choice for the high-reward lever was observed. The effects of
      estradiol, PPT, and DPN were more pronounced 24 h post-administration, suggesting
      that these effects may be genomic in nature. Together, these results demonstrate
      that estradiol modulates cost/benefit decision making in females, whereby
      concomitant activation of ERalpha and beta receptors shifts the decision criteria
      and reduces preference for larger, yet more costly rewards.

PMID- 21881568
TI  - Activation of nociceptin/orphanin FQ peptide receptors disrupts visual but not
      auditory sensorimotor gating in BALB/cByJ mice: comparison to dopamine receptor
      agonists.
AB  - Nociceptin/orphanin FQ (N/OFQ) peptide and its receptor (NOP receptor) have been
      implicated in a host of brain functions and diseases, but the contribution of
      this neuropeptide system to behavioral processes of relevance to psychosis has
      not been investigated. We examined the effect of the NOP receptor antagonists,
      Compound 24 and J-113397, and the synthetic agonist, Ro64-6198, on time function
      (2-2000 ms prepulse-pulse intervals) of acoustic (80 dB/10 ms prepulse) and
      visual (1000 Lux/20 ms prepulse) prepulse inhibition of startle reflex (PPI), a
      preattentive sensory filtering mechanism that is central to perceptual and mental
      integration. The effects of the dopamine D1-like receptor agonist, SKF-81297, the
      D2-like receptor agonist, quinelorane, and the mixed D1/D2 agonist, apomorphine,
      were studied for comparison. When acoustic stimulus was used as prepulse,
      BALB/cByJ mice displayed a monotonic time function of PPI, and consistent with
      previous studies, apomorphine and SKF-81279 induced PPI impairment, whereas
      quinelorane had no effect. None of the NOP receptor ligands was effective on
      acoustic PPI. When flash light was used as prepulse, BALB/cByJ mice displayed a
      bell-shaped time function of PPI and all dopamine agonists were active. Ro64-6198
      was also effective in reducing visual PPI. NOP receptor antagonists showed no
      activity but blocked disruptive effect of Ro64-6198. Finally, coadministration of
      the typical antipsychotic, haloperidol, attenuated PPI impairment induced by Ro64
      6198, revealing involvement of a dopaminergic component. These findings show that
      pharmacological stimulation of NOP or dopamine D2-like receptors is more potent
      in disrupting visual than acoustic PPI in mice, whereas D1-like receptor
      activation disrupts both. They further suggest that dysfunction of N/OFQ
      transmission may be implicated in the pathogenesis of psychotic manifestations.

PMID- 21881569
TI  - A randomized trial on mineralocorticoid receptor blockade in men: effects on
      stress responses, selective attention, and memory.
AB  - Corticosteroids, released in high amounts after stress, exert their effects via
      two different receptors in the brain: glucocorticoid receptors (GRs) and
      mineralocorticoid receptors (MRs). GRs have a role in normalizing stress-induced
      effects and promoting consolidation, while MRs are thought to be important in
      determining the threshold for activation of the hypothalamic-pituitary-adrenal
      (HPA) axis. We investigated the effects of MR blockade on HPA axis responses to
      stress and stress-induced changes in cognitive function. In a double-blind,
      placebo-controlled study, 64 healthy young men received 400 mg of the MR
      antagonist spironolactone or placebo. After 1.5 h, they were exposed to either a
      Trier Social Stress Test or a non-stressful control task. Responses to stress
      were evaluated by hormonal, subjective, and physiological measurements.
      Afterwards, selective attention, working memory, and long-term memory performance
      were assessed. Spironolactone increased basal salivary cortisol levels as well as
      cortisol levels in response to stress. Furthermore, spironolactone significantly
      impaired selective attention, but only in the control group. The stress group
      receiving spironolactone showed impaired working memory performance. By contrast,
      long-term memory was enhanced in this group. These data support a role of MRs in
      the regulation of the HPA axis under basal conditions as well as in response to
      stress. The increased availability of cortisol after spironolactone treatment
      implies enhanced GR activation, which, in combination with MR blockade,
      presumably resulted in a decreased MR/GR activation ratio. This condition
      influences both selective attention and performance in various memory tasks.

PMID- 21881570
TI  - Abnormal glucocorticoid receptor mRNA and protein isoform expression in the
      prefrontal cortex in psychiatric illness.
AB  - Stress has been implicated in the onset and illness course of schizophrenia and
      bipolar disorder. The effects of stress in these disorders may be mediated by
      abnormalities of the hypothalamic-pituitary-adrenal axis, and its corticosteroid
      receptors. We investigated mRNA expression of the glucocorticoid receptor (GR)
      and mineralocorticoid receptor (MR), and protein expression of multiple GRalpha
      isoforms, in the prefrontal cortex of 37 schizophrenia cases and 37 matched
      controls. Quantitative real-time PCR, western blotting, and luciferase assays
      were employed. In multiple regression analysis, schizophrenia diagnosis was a
      significant predictor of total GR mRNA expression (p<0.05), which was decreased
      (11.4%) in schizophrenia cases relative to controls. No significant effect of
      diagnosis on MR mRNA was detected. At the protein level, no significant
      predictors of total GRalpha protein or the full-length GRalpha isoform were
      identified. However, schizophrenia diagnosis was a strong predictor (p<0.0005) of
      the abundance of a truncated ~ 50 kDa GRalpha protein isoform, putative GRalpha
      D1, which was increased in schizophrenia cases (80.4%) relative to controls. This
      finding was replicated in a second cohort of 35 schizophrenia cases, 34 bipolar
      disorder cases, and 35 controls, in which both schizophrenia and bipolar disorder
      diagnoses were significant predictors of putative GRalpha-D1 abundance (p<0.05
      and p=0.005, respectively). Full-length GRalpha was increased in bipolar disorder
      relative to schizophrenia cases. Luciferase assays demonstrated that the GRalpha
      D1 isoform can activate transcription at glucocorticoid response elements. These
      findings confirm total GR mRNA reductions in schizophrenia and provide the first
      evidence of GR protein isoform abnormalities in schizophrenia and bipolar
      disorder.

PMID- 21881572
TI  - Influenza A facilitates sensitization to house dust mite in infant mice leading
      to an asthma phenotype in adulthood.
AB  - The origins of allergic asthma, particularly in infancy, remain obscure.
      Respiratory viral infections and allergen sensitization in early life have been
      associated with asthma in young children. However, a causal link has not been
      established. We investigated whether an influenza A infection in early life
      alters immune responses to house dust mite (HDM) and promotes an asthmatic
      phenotype later in life. Neonatal (8-day-old) mice were infected with influenza
      virus and 7 days later, exposed to HDM for 3 weeks. Unlike adults, neonatal mice
      exposed to HDM exhibited negligible immune responsiveness to HDM, but not to
      influenza A. HDM responsiveness in adults was associated with distinct Ly6c+
      CD11b+ inflammatory dendritic cell and CD8alpha+ plasmacytoid (pDC) populations
      that were absent in HDM-exposed infant mice, suggesting an important role in HDM
      mediated inflammation. Remarkably, HDM hyporesponsiveness was overcome when
      exposure occurred concurrently with an acute influenza infection; young mice now
      displayed robust allergen-specific immunity, allergic inflammation, and lung
      remodeling. Remodeling persisted into early adulthood, even after prolonged
      discontinuation of allergen exposure and was associated with marked impairment of
      lung function. Our data demonstrate that allergen exposure coincident with acute
      viral infection in early life subverts constitutive allergen hyporesponsiveness
      and imprints an asthmatic phenotype in adulthood.

PMID- 21881571
TI  - Enhanced sensitivity to attenuation of conditioned reinstatement by the mGluR 2/3
      agonist LY379268 and increased functional activity of mGluR 2/3 in rats with a
      history of ethanol dependence.
AB  - Recent findings implicate group II metabotropic glutamate receptors (mGluR(2/3))
      in the reinforcing and dependence-inducing actions of ethanol and identify these
      receptors as treatment targets for alcoholism. Here, we investigated the effects
      of mGLuR(2/3) activation on conditioned reinstatement in rats with different
      ethanol-dependence histories and examined dependence-associated changes in the
      functional activity of mGluR(2/3). Following ethanol self-administration training
      and conditioning procedures, rats were made ethanol dependent, using ethanol
      vapor inhalation, under three conditions: a single intoxication and withdrawal
      episode (SW), repeated cycles of intoxication and withdrawal (RW), or no
      intoxication (CTRL). At 1 week after removal from ethanol vapor, self
      administration resumed until stable baseline performance was reached, followed by
      extinction of operant responding and reinstatement tests. Post-withdrawal self
      administration was increased in the RW group, but all groups showed conditioned
      reinstatement. The mGluR(2/3) agonist LY379268 dose -dependently reduced
      reinstatement in all groups, but was more effective at low doses in the SW and RW
      groups. The highest dose of LY379268 tested reduced spontaneous locomotor
      activity and operant responding maintained by a non-drug reinforcer, without
      differences among groups. The heightened sensitivity to the effects of LY379268
      in rats with an ethanol-dependence history was therefore specific to behavior
      motivated by ethanol-related stimuli. Both the SW and RW groups showed elevated
      [(35)S]GTPgammaS binding in the central nucleus of the amygdala (CeA) and bed
      nucleus of stria terminalis (BNST), relative to the CTRL group. The findings
      implicate changes in mGluR(2/3) functional activity as a factor in ethanol
      dependence and support treatment target potential of mGlu(2/3) receptors for
      craving and relapse prevention.

PMID- 21881573
TI  - Enhanced HIV-1 replication in ex vivo ectocervical tissues from post-menopausal
      women correlates with increased inflammatory responses.
AB  - Knowledge about early innate immune responses at the mucosal surfaces of the
      female genital tract is important in understanding the pathogenesis of
      heterosexual transmission of human immunodeficiency virus type-1 (HIV-1). As
      estradiol decreases inflammatory responses, we postulated that an estradiol
      deficient state such as post-menopause could enhance expression of inflammatory
      factors that stimulate HIV-1 replication. We compare HIV-1 integration,
      transcription, and viral p24 release levels among ectocervical tissues obtained
      from pre- and post-menopausal donors. We detected enhanced HIV-1 p24 release
      levels in post- compared with pre-menopausal tissues (P<0.0001), but saw no
      difference in HIV-1 integration. Overall, 100% of post-menopausal tissues
      exhibited levels of HIV-1 transcription above background compared with only 60%
      of pre-menopausal tissues. Increased HIV-1 transcription was associated with
      enhanced interleukin (IL)-1beta, IL-6, monocyte chemotactic protein-1, growth
      regulated oncogene-alpha, and interferon-gamma-inducible protein-10 expression.
      Neutralization and nuclear factor-kappaB-targeting small-interfering RNA
      experiments both decreased HIV-1 transcription, suggesting that the early
      inflammatory response may facilitate HIV-1 replication in ex vivo ectocervical
      tissues from post-menopausal women.

PMID- 21881574
TI  - Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized
      hypertensive rats through inhibition of the N-type calcium channel.
AB  - Both osteoporosis and high blood pressure are major diseases in aging
      populations. Recent studies demonstrated that some antihypertensive drugs reduced
      the risk of bone fracture in elderly patients. Although calcium channel blockers
      (CCB) are widely used as first-line antihypertensive agents, there is no evidence
      that they prevent osteoporosis. In this study, we investigated the effects of two
      types of CCB on bone metabolism: cilnidipine (L-/N-type CCB), which suppresses
      norepinephrine release from the sympathetic nerve, and amlodipine (L-type CCB).
      In ovariectomized female spontaneous hypertensive rats, administration of
      cilnidipine, but not amlodipine, resulted in a significant increase in the ratio
      of alkaline phosphatase to tartrate-resistant acid phosphatase (TRAP) and a
      decrease in the number of osteoclasts, as assessed by TRAP staining in the
      proximal tibia. Bone mineral density, moreover, was significantly higher in the
      cilnidipine group as compared with the amlodipine group and was associated with a
      significant decrease in a urinary collagen degradation product
      (deoxypyridinoline). The degree of prevention of osteoporosis by cilnidipine was
      similar to that of carvedilol (a beta-blocker) because beta-blockers reduce
      fracture risks though the inhibition of osteoclast activation. Interestingly,
      these effects cannot be attributed to the reduction of blood pressure because all
      three drugs significantly decreased blood pressure. In contrast, both cilnidipine
      and carvedilol, but not amlodipine, significantly decreased heart rate,
      indicating that both cilnidipine and carvedilol suppressed sympathetic nervous
      activity. Overall, our present data showed that cilnidipine (L-/N-type CCB)
      ameliorated osteoporosis in ovariectomized hypertensive rats. These pleiotropic
      effects of antihypertensive drugs such as cilnidipine and carvedilol might
      provide additional benefits in the treatment of hypertensive postmenopausal
      women.

PMID- 21881575
TI  - Prevention of perinatal death with low-dose aspirin in developing countries.

PMID- 21881576
TI  - Home monitoring is the optimal method for assessing blood pressure variability.

PMID- 21881577
TI  - Characteristics of blood pressure profiles and vascular dysfunction.

PMID- 21881578
TI  - Association between the angiotensinogen gene T174M polymorphism and hypertension
      risk in the Chinese population: a meta-analysis.
AB  - No consensus has been reached on the association between the angiotensinogen gene
      polymorphism T174M and hypertension risk in the Chinese population. We conducted
      a meta-analysis to systematically pursue their possible association. Case-control
      studies in the Chinese and English publications were identified by searching the
      MEDLINE, EMBASE, CBM, CNKI, Wanfang and VIP databases. The fixed-effects model
      and the random-effects model were applied for dichotomous outcomes to combine the
      results of the individual studies. After this, we selected 16 studies that met
      the inclusion criteria. In total, the selected studies contributed a study
      population containing 3828 hypertensive patients and 3251 normotensive controls.
      We found no statistical association between the T174M polymorphism and
      hypertension risk in all subjects, in a Han Chinese subgroup or in non-Han
      Chinese minorities. However, a statistically significant association was observed
      between the T174M polymorphism and a hypertensive group (systolic blood pressure
      >=160 mm Hg and/or diastolic blood pressure >=95 mm Hg) in the dominant genetic
      model (MM+MT vs. TT: P=0.03, odds ratio=1.71, 95% confidence interval 1.07-2.74,
      P(heterogeneity)=0.27, I(2)=24%, fixed-effects model). No evidence of publication
      bias was observed. More studies, especially studies stratified for different
      stages of hypertension, should be performed in the future to fully examine this
      question. Studies investigating gene-gene interactions, gene-environment
      interactions, as well as their mutual interactions will also be important.

PMID- 21881579
TI  - Prevention of gravidic endothelial hypertension by aspirin treatment administered
      from the 8th week of gestation.
AB  - The aim of this study was to evaluate whether low doses of aspirin (100 mg per
      day) administered to a homogeneous population of women early (8-10 weeks) during
      their first pregnancy improved the outcome of gestation hypertensive disorders.
      This study was performed at the Blida Hospital, where many early deliveries and
      pregnancy complications are observed. A total of 164 women were either treated
      (82) or used as controls (82). Treatment increased the gestation length by 12
      days on average, thus triggering an approximate 150-g increase in newborn weight.
      This consistently improved the outcome for all patients with respect to all
      parameters investigated. Overall, the relative risk of developing hypertensive
      disorders of gestation was reduced to 0.07 (confidence interval=0.01-0.51). In
      our series, we did not observe deleterious consequences for the fetus
      (teratogenicity and fetotoxicity) or adverse outcomes for the mothers. Despite
      the limited number of patients analyzed, the present study is one of the largest
      investigating early aspirin treatment of gestational hypertensive diseases. In
      addition, the time of aspirin administration is among the earliest yet examined.
      The data tend to confirm the results obtained from other cohorts on the overall
      benefit of aspirin treatment for gestational disorders. In the future, molecular
      or ultrasonographic markers of these diseases could help to screen patients
      before applying the treatment.

PMID- 21881580
TI  - Chronic kidney disease, 24-h blood pressure burden and their effects on silent
      cerebral injury and cognitive impairment: might age serve as a modulator?

PMID- 21881581
TI  - Is CKD a surrogate marker for predicting cognitive impairment?

PMID- 21881582
TI  - UBE3C genetic variations as potent markers of nasal polyps in Korean asthma
      patients.
AB  - The human ubiquitin protein ligase E3C (UBE3C) regulates airway inflammatory
      responses and is hypothesized to be associated with the presence of nasal polyps
      in asthma-related diseases. A total of 24 UBE3C single-nucleotide polymorphisms
      (SNPs) were genotyped in a 467 Korean asthma cohort that was stratified into more
      homogenous phenotypes of 114 aspirin-exacerbated respiratory disease subgroup and
      353 aspirin-tolerant asthma (ATA) subjects. Association analysis revealed that 16
      UBE3C SNPs were significantly associated with presence of nasal polyps in the
      overall asthma group (P=0.0008 and P(corr)=0.01; odds ratio (OR)=0.60). The
      strength of association from 10 polymorphisms was increased in the ATA subgroup
      (P=0.0002 and P(corr)=0.003; OR=0.49). In addition, UBE3C_ht1 was found to be
      consistently associated with nasal polyps in the overall asthmatics group
      (P=0.006) and the ATA phenotype (P=0.002; P(corr)=0.02) via a codominant
      mechanism. Our findings provide evidence that variations in UBE3C are potent
      genetic markers of nasal polyps development in Korean asthmatics and may
      contribute novel insights into the clinical relevance and potential involvement
      of UBE3C in respiratory deficiencies.

PMID- 21881583
TI  - CD9 is critical for cutaneous wound healing through JNK signaling.
AB  - Cutaneous injury triggers a cascade of signaling events essential for wound re
      epithelialization. CD9, a cell-surface protein, has been implicated in a number
      of cellular processes by coupling to intracellular signaling; however, its exact
      role in wound healing remains unidentified. We reported that CD9 was
      downregulated in migrating epidermis, and reelevated to basal level when re
      epithelialization was completed. Although low level of CD9 appears to be required
      for normal wound healing, a significant healing delay was found in CD9-null mice,
      with wounds gaping wider on day 5 and day 7 post wounding. Further analysis
      showed that re-epithelialization was adversely affected in CD9-null mice, due to
      impaired migration of epidermis. Notably, CD9 deficiency caused a persistent
      enhancement of C-JUN NH2 terminal kinase (JNK) signaling primarily in migrating
      epidermis with abnormal elevation of matrix metalloproteinase (MMP)-9 detected in
      CD9-null wounds, leading to excessive degradation of type IV collagen, and thus a
      defective basement membrane at the wound site. JNK suppression reduced MMP-9
      production and therefore ameliorated the healing delay with the appearance of
      significantly elongated migrating epidermis in CD9-null mice. Our study
      demonstrated the importance of CD9 in wound re-epithelialization, linking this
      molecule directly to basement membrane formation and epidermal migration through
      participating in the regulation of the JNK/MMP-9 pathway.

PMID- 21881584
TI  - Inter-regulation of Th17 cytokines and the IL-36 cytokines in vitro and in vivo:
      implications in psoriasis pathogenesis.
AB  - Accumulating evidence indicates that IL-1 family members and Th17 cytokines have
      a pathogenic role in psoriasis. We investigated the regulatory interactions of
      the IL-1-like IL-36 cytokine family and the Th17 cytokines in the context of skin
      inflammation. We observed increased gene expression of all three IL-36 cytokines
      in a Th17-dominant psoriasis-like animal model. The induction was downregulated
      by neutralizing IL-22. Expression of the IL-36s was also induced in cultured
      primary human keratinocytes (KC) by IL-17A and tumor necrosis factor (TNF)-alpha,
      and IL-22 synergized with IL-17A and TNF-alpha. Furthermore, the IL-36s directly
      induced their own expression and the production of proinflammatory mediators (TNF
      alpha, IL-6, IL-8) in KC. These functions were markedly enhanced with the
      addition of IL-17A or TNF-alpha to the cultures. Similarly, IL-36alpha and IL
      36beta augmented IL-17A-mediated induction of antibacterial peptides. Finally, we
      show that the increased gene expression of IL-36 correlated with Th17 cytokines
      in the lesions of psoriatic patients. Our results indicate that the IL-36
      cytokines are not only regulated by Th17 cytokines, but that they themselves can
      regulate the expression and enhance the function of Th17 cytokines. We propose
      that a feedback loop between the IL-36 and Th17 cytokines is involved in driving
      cytokine expression in psoriatic tissues.

PMID- 21881585
TI  - Dihydrotestosterone-inducible IL-6 inhibits elongation of human hair shafts by
      suppressing matrix cell proliferation and promotes regression of hair follicles
      in mice.
AB  - Autocrine and paracrine factors are produced by balding dermal papilla (DP) cells
      following dihydrotestosterone (DHT)-driven alterations and are believed to be key
      factors involved in male pattern baldness. Herein we report that the IL-6 is
      upregulated in balding DP cells compared with non-balding DP cells. IL-6 was
      upregulated 3  hours after 10-100  nM DHT treatment, and ELISA showed that IL-6
      was secreted from balding DP cells in response to DHT. IL-6 receptor (IL-6R) and
      glycoprotein 130 (gp130) were expressed in follicular keratinocytes, including
      matrix cells. Recombinant human IL-6 (rhIL-6) inhibited hair shaft elongation and
      suppressed proliferation of matrix cells in cultured human hair follicles.
      Moreover, rhIL-6 injection into the hypodermis of mice during anagen caused
      premature onset of catagen. Taken together, our data strongly suggest that DHT
      inducible IL-6 inhibits hair growth as a paracrine mediator from the DP.

PMID- 21881586
TI  - Engineering melanoma progression in a humanized environment in vivo.
AB  - To overcome the lack of effective therapeutics for aggressive melanoma, new
      research models closely resembling the human disease are required. Here we report
      the development of a fully orthotopic, humanized in vivo model for melanoma,
      faithfully recapitulating human disease initiation and progression. To this end,
      human melanoma cells were seeded into engineered human dermo-epidermal skin
      substitutes. Transplantation onto the back of immunocompromised rats consistently
      resulted in the development of melanoma, displaying the hallmarks of their
      parental tumors. Importantly, all initial steps of disease progression were
      recapitulated, including the incorporation of the tumor cells into their
      physiological microenvironment, transition of radial to vertical growth, and
      establishment of highly vascularized, aggressive tumors with dermal involvement.
      Because all cellular components can be individually accessed using this approach,
      it allows manipulation of the tumor cells, as well as of the keratinocyte and
      stromal cell populations. Therefore, in one defined model system, tumor cell
      autonomous and non-autonomous pathways regulating human disease progression can
      be investigated in a humanized, clinically relevant context.

PMID- 21881587
TI  - Characterization of the DNA copy-number genome in the blood of cutaneous T-cell
      lymphoma patients.
AB  - Cutaneous T-cell lymphoma (CTCL) is a heterogeneous non-Hodgkin's lymphoma that
      may variably involve the skin, lymph nodes, and peripheral blood. Malignant
      burden ranges from cutaneous patches and plaques with little evidence of blood
      involvement to erythroderma often in association with frank leukemia, as in
      Sezary syndrome. Toward a better understanding of the pathogenesis of this CD4+ T
      cell malignancy, we conducted a high-resolution genomic analysis combining DNA
      (23 samples) and mRNA (12 samples) data of peripheral blood isolates from CTCL
      patients across a spectrum of stages. Strikingly, even patients with limited
      involvement, e.g., normal CD4 counts, contained significant copy-number
      alterations. Defining genomic characteristics of CTCL blood involvement included
      gains on 8q and 17q, and deletions on 17p and chromosome 10. A consensus analysis
      of 108 leukemic CTCL samples demonstrated global similarities among patients with
      varied blood involvement, narrowing 38 of 62 loci. Toward an annotated framework
      for in vitro testing, we also characterized genomic alterations in five CTCL cell
      lines (HH, HUT78, PNO, SeAx, and Sez4), revealing intact core features of
      leukemic CTCL. Together, these studies produce the most comprehensive view of the
      leukemic CTCL genome to date, with implications for pathogenesis, molecular
      classification, and potential future therapeutic developments.

PMID- 21881588
TI  - Can we rely on the Dermatology Life Quality Index as a measure of the impact of
      psoriasis or atopic dermatitis?
AB  - The Dermatology Life Quality Index (DLQI) is a widely used health-related quality
      of life measure. However, little research has been conducted on its
      dimensionality. The objectives of the current study were to apply Rasch analysis
      to DLQI data to determine whether the scale is unidimensional, to assess its
      measurement properties, test the response format, and determine whether the
      measure exhibits differential item functioning (DIF) by disease (atopic
      dermatitis versus psoriasis), gender, or age group. The results show that there
      were several problems with the scale, including misfitting items, DIF by disease,
      age, and gender, disordered response thresholds, and inadequate measurement of
      patients with mild illness. As the DLQI did not benefit from the application of
      Rasch analysis in its development, it is argued that a new measure of disability
      related to dermatological disease is required. Such a measure should use a
      coherent measurement model and ensure that items are relevant to all potential
      respondents. The current use of the DLQI as a guide to treatment selection is of
      concern, given its inadequate measurement properties.

PMID- 21881589
TI  - Ryanodine receptors are expressed in epidermal keratinocytes and associated with
      keratinocyte differentiation and epidermal permeability barrier homeostasis.
AB  - Ryanodine receptors (RyRs) have an important role as calcium channels in the
      regulation of intracellular calcium levels in the nervous system and muscle. In
      the present study, we investigated the expression of RyR in human epidermis.
      Immunohistochemical studies and reverse transcription-PCR indicated the
      expression of RyR type 1, 2, and 3 proteins in epidermal keratinocytes. The
      expression level of each RyR subtype was higher in differentiating keratinocytes
      than in proliferative cells. We also demonstrated the functional expression of
      RyR by calcium imaging. In cultured human keratinocytes, application of the RyR
      agonist 4-chloro-m-cresol (CMC) induced elevation of the intracellular calcium
      concentration, and co-application of the RyR antagonist 1,1'-diheptyl-4,4'
      bipyridinium dibromide (DHBP) blocked the elevation. Application of CMC
      accelerated keratinocyte differentiation in vitro. On the other hand, topical
      application of CMC after tape-stripping of hairless mouse skin delayed barrier
      recovery, whereas application of an RyR antagonist, dantrolene or DHBP,
      accelerated the barrier recovery. These results suggest that RyR expressed in
      epidermal keratinocytes is associated with both differentiation of keratinocytes
      and epidermal barrier homeostasis.

PMID- 21881590
TI  - Human keratinocytes' response to injury upregulates CCL20 and other genes linking
      innate and adaptive immunity.
AB  - In the early stages of wound healing, keratinocytes (KCs) become "activated" and
      release inflammatory molecules such as IL-1 and IL-8, which are linked to innate
      immune responses and neutrophil recruitment. It is unclear, however, whether KCs
      release molecules linked to adaptive immune responses, e.g., CCL20, in their
      early state of activation without signals from infiltrating T cells. This study
      aims to isolate the immediate alterations in protective and inflammatory gene
      expression that occur in epidermal KCs, with a particular focus on molecules
      associated with cell-mediated immunity. We used dispase-separated epidermis,
      followed by intercellular disassociation by trypsinization, as a model for
      epidermal injury. We obtained a pure population of KCs using flow cytometry. As a
      control for uninjured epidermis, we performed laser capture microdissection on
      normal human skin. Sorted KCs had an early burst of upregulated gene expression,
      which included CCL20, IL-15, IL-23A, IFN-kappa, and several antimicrobial
      peptides. Our results provide insight into the potential role of KCs as
      contributors to cell-mediated inflammation, and expand knowledge about gene
      modulation that occurs during early wound healing. Our findings may be relevant
      to cutaneous diseases such as psoriasis, where micro-injury can trigger the
      formation of psoriatic plaques at the site of trauma.

PMID- 21881592
TI  - Oral administration of oleic or linoleic acid accelerates the inflammatory phase
      of wound healing.
AB  - The effects of oral ingestion of oleic (OLA) and linoleic (LNA) acids on wound
      healing in rats were investigated. LNA increased the influx of inflammatory
      cells, the concentration of hydrogen peroxide (H(2)O(2)) and cytokine-induced
      neutrophil chemoattractant-2alphabeta (CINC-2alphabeta), and the activation of
      the transcription factor activator protein-1 (AP-1) in the wound at 1  hour post
      wounding. LNA decreased the number of inflammatory cells and IL-1, IL-6, and
      macrophage inflammatory protein-3 (MIP-3) concentrations, as well as NF-kappaB
      activation in the wound at 24  hours post wounding. LNA accelerated wound closure
      over a period of 7 days. OLA increased TNF-alpha concentration and NF-kappaB
      activation at 1  hour post wounding. A reduction of IL-1, IL-6, and MIP-3alpha
      concentrations, as well as NF-kappaB activation, was observed 24  hours post
      wounding in the OLA group. These data suggest that OLA and LNA accelerate the
      inflammatory phase of wound healing, but that they achieve this through different
      mechanisms.

PMID- 21881593
TI  - High levels of CCL26 in blister fluid and sera of patients with bullous
      pemphigoid.

PMID- 21881594
TI  - Relationship between disease activity and type 1 interferon- and other cytokine
      inducible gene expression in blood in dermatomyositis and polymyositis.
AB  - The objective of this study was to evaluate the relationship between blood mRNA,
      disease activity and treatment effects in a longitudinal study of patients with
      dermatomyositis (DM) or polymyositis (PM). In all, 24 patients with DM or PM were
      followed for up to 6 years (mean of 1.9 years) at 2-7 follow-up visits while
      receiving standard clinical care. Clinical data and blood samples collected at 80
      patient visits were used for the analysis of cytokine-induced gene expression for
      the signaling pathways of type 1 interferon (IFN), tumor necrosis factor-alpha,
      IL-1beta, granulocyte-monocyte colony-stimulating factor, IL-10 and IL-13. A type
      1 IFN signature score, but not other cytokine signature scores in the blood of
      patients with DM or PM, correlated highly with disease activity, decreased
      significantly with immunomodulatory therapies and showed concordant changes with
      major changes in disease activity. Type 1 IFN signature score in the blood
      correlates with disease activity in longitudinal follow-up of individual patients
      with DM or PM. The type 1 IFN-inducible gene transcripts in the blood have
      potential utility for monitoring disease activity in patients with DM or PM.

PMID- 21881595
TI  - Systemic in vivo lentiviral delivery of miR-15a/16 reduces malignancy in the NZB
      de novo mouse model of chronic lymphocytic leukemia.
AB  - Similar to human chronic lymphocytic leukemia (CLL), the de novo New Zealand
      Black (NZB) mouse model has a genetically determined age-associated increase in
      malignant B-1 clones and decreased expression of microRNAs miR-15a and miR-16 in
      B-1 cells. In the present study, lentiviral vectors were employed in vivo to
      restore miR-15a/16, and both the short-term single injection and long-term
      multiple injection effects of this delivery were observed in NZB. Control
      lentivirus without the mir-15a/16 sequence was used for comparison. We found that
      in vivo lentiviral delivery of mir-15a/16 increased miR-15a/16 expression in
      cells that were transduced (detected by GFP expression) and in sera when compared
      with control lentivirus treatment. More importantly, mice treated with the miR
      expressing lentivirus had decreased disease. The lentivirus had little systemic
      toxicity while preferentially targeting B-1 cells. Short-term effects on B-1
      cells were direct effects, and only malignant B-1 cells transduced with miR
      15a/16 lentivirus had decreased viability. In contrast, long-term studies
      suggested both direct and indirect effects resulting from miR-15a/16 lentivirus
      treatment. A decrease in B-1 cells was found in both the transduced and non
      transduced populations. Our data support the potential use of systemic lentiviral
      delivery of miR-15a/16 to ameliorate disease manifestations of CLL.

PMID- 21881597
TI  - Low-dose atorvastatin reduces ambulatory blood pressure in patients with mild
      hypertension and hypercholesterolaemia: a double-blind, randomized, placebo
      controlled study.
AB  - Among several beneficial cardiovascular actions of statins, experimental studies
      have suggested that statins may also induce a mild blood pressure (BP) reduction.
      However, clinical data were controversial and the potential hypotensive statin
      effect remains uncertain. This study aimed to investigate the effect of
      atorvastatin on ambulatory BP in patients with mild hypertension and
      hypercholesterolaemia. A total of 50 patients with mild hypertension and
      hypercholesterolaemia participated in this double-blind, randomized, placebo
      controlled study. Patients were randomized to either 10 mg atorvastatin or
      placebo for 26 weeks. Background antihypertensive treatment, if any, remained
      unchanged during follow-up. At baseline and study-end (26 weeks), ambulatory BP
      monitoring and blood sampling for determination of standard biochemical and
      safety parameters were performed in all participants. BP loads were defined as
      the percentage of BP measurements exceeding the hypertension threshold of 140/90
      mm Hg for daytime and 125/75 mm Hg nighttime period. Atorvastatin significantly
      reduced 24-h systolic and diastolic BP (DBP; median (range)) as compared with
      placebo (-5.0 (-21.0, 4.0) vs +1.0 (-6.0, 7.0) mm Hg, P<0.001 and -3.0 (-16.0,
      2.0) vs +0.1 (-7, 4) mm Hg, P<0.01, respectively). Reductions in systolic and DBP
      loads during follow-up were also evident in the atorvastatin, but not in the
      placebo group. BP-lowering effects of atorvastatin were consistent in both
      daytime and nighttime periods. This study shows a mild, but consistent throughout
      the 24-h period BP-lowering effect of atorvastatin in patients with mild
      hypertension and hypercholesterolaemia. This beneficial effect of atorvastatin on
      BP may represent another pathway through which this drug class provides
      cardiovascular risk reduction.

PMID- 21881598
TI  - High prevalence and low awareness, treatment and control of hypertension in Asian
      Indian women.
AB  - Hypertension is an important public health problem in India. To determine its
      prevalence, awareness, treatment and control among women, we performed a
      nationwide study. Population-based studies among women aged 35-70 years were
      performed in four urban and five rural locations. Stratified sampling was
      performed and we enrolled 4608 (rural 2604 and urban 2004) of the targeted 8000
      (57%). Demographic details, medical history, diet, physical activity,
      anthropometry and blood pressure (BP) were recorded. Descriptive statistics are
      reported. Logistic regression was performed to determine the association of
      hypertension and its awareness, treatment and control with socioeconomic factors.
      Age-adjusted prevalence of hypertension (known or BP>=140/>=90 mm Hg) was
      observed in 1672 women (39.2%) (rural 746, 31.5%; urban 926, 48.2%). Significant
      determinants of hypertension were urban location, greater literacy, high dietary
      fat, low fibre intake, obesity and truncal obesity (P<0.01). Hypertension
      awareness was noted in 727 women (42.8%), more in urban (529, 56.8%) than in
      rural (198, 24.6%). Of these, 38.6% of the women were on treatment (urban 35.7,
      rural 46.5) and of those treated, controlled blood pressure (<140 and <90 mm Hg)
      was observed in 21.5% (urban 28.3 vs 10.2). Among hypertensive subjects,
      treatment was noted in 18.3% (rural 13.1, urban 22.5) and control in 3.9% (rural
      1.3, urban 5.9). A significant determinant of low awareness, treatment and
      control was rural location (multivariate-adjusted P<0.05). There is a high
      prevalence of hypertension in middle-aged Asian Indian women. Very low awareness,
      treatment and control status are observed.

PMID- 21881596
TI  - A spectrum of susceptibility to rheumatoid arthritis within HLA-DRB1:
      stratification by autoantibody status in a large UK population.
AB  - Previously-proposed rheumatoid arthritis (RA) HLA-DRB1 susceptibility and
      protective models were compared, based on amino acids at positions 67-74 and
      autoantibody combinations. 3 657 RA patients and 1 357 controls were studied
      using logistic regression, with secondary stratification by anti-citrullinated
      peptide antibodies(ACPA) and rheumatoid factor(RF). Susceptibility models were
      based on previously defined HLA-DRB1 shared epitope(SE) subgroups. (70)DERAA(74),
      D(70) and I(67) protective models were compared, adjusting for HLA-DRB1 SE. A
      hierarchy of risk was observed within the HLA-DRB1 SE, particularly for ACPA
      positive and RF-positive RA: HLA-DRB1(*)0401~(*)0404>(*)0101~(*)1001
      ((*)0404>(*)0101: P=0.0003). HLA-DRB1(*)0401/(*)0404 compound heterozygosity
      conferred a risk similar to (*)0401 homozygosity (P=0.70). Protective effects of
      D(70) and I(67) were similar. Predictions of the D(70) model fitted the data
      better than those of the I(67) model. The protective effect of D(70) showed a
      gene-dose effect (OR 0.82, 95% CI 0.73-0.92, P=5.8 * 10(-4)), but was only seen
      in RA patients positive for RF or ACPA. HLA-DRB1 SE alleles were also associated
      with ACPA-negative, RF-positive RA (OR 1.42 (1.15-1.76), P=0.0012). In
      conclusion, HLA-DRB1 SE alleles show heterogeneity in RA susceptibility; their
      major effect appears to be mediated by ACPA positivity, but a significant
      association of HLA-DRB1 SE with RF-positive, ACPA-negative RA was also observed.
      D(70) specifically protected against antibody-positive RA.

PMID- 21881599
TI  - Cell death regulation during influenza A virus infection by matrix (M1) protein:
      a model of viral control over the cellular survival pathway.
AB  - During early infection, viruses activate cellular stress-response proteins such
      as heat-shock proteins (Hsps) to counteract apoptosis, but later on, they
      modulate these proteins to stimulate apoptosis for efficient viral dissemination.
      Hsp70 has been attributed to modulate viral entry, transcription, nuclear
      translocation and virion formation. It also exerts its anti-apoptotic function by
      binding to apoptosis protease-activating factor 1 (Apaf-1) and disrupting
      apoptosome formation. Here, we show that influenza A virus can regulate the anti
      apoptotic function of Hsp70 through viral protein M1 (matrix 1). M1 itself did
      not induce apoptosis, but enhanced the effects of apoptotic inducers. M1-small
      interfering RNA inhibits virus-induced apoptosis in cells after either virus
      infection or overexpression of the M1 protein. M1 binds to Hsp70, which results
      in reduced interaction between Hsp70 and Apaf-1. In a cell-free system, the M1
      protein mediates procaspase-9 activation induced by cytochrome c/deoxyadenosine
      triphosphate. A study involving deletion mutants confirmed the role of the C
      terminus substrate-binding domain (EEVD) of Hsp70 and amino acids 128-165 of M1
      for this association. The M1 mutants, which did not co-immunoprecipitate with
      Hsp70, failed to induce apoptosis. Overall, the study confirms the proapoptotic
      function of the M1 protein during influenza virus infection.

PMID- 21881600
TI  - The p75 receptor mediates axon growth inhibition through an association with PIR
      B.
AB  - The Nogo receptor and paired immunoglobulin-like receptor B (PIR-B) are receptors
      for three myelin-derived axon-growth inhibitors, including myelin-associated
      glycoprotein (MAG). In this study, we report that the p75 receptor is required
      for the signal transduction of PIR-B, which interacted with p75 upon ligand
      binding. In addition, p75 was required for activation of Src homology 2
      containing protein tyrosine phosphatase (SHP), which is induced by MAG binding to
      PIR-B. Mice carrying a mutation in the p75 gene showed promotion of axonal
      regeneration after optic nerve injury. Thus, our results indicate that p75 has a
      critical role in axon growth inhibition in specific neuronal tracts.

PMID- 21881601
TI  - Metformin inhibits melanoma development through autophagy and apoptosis
      mechanisms.
AB  - Metformin is the most widely used antidiabetic drug because of its proven
      efficacy and limited secondary effects. Interestingly, recent studies have
      reported that metformin can block the growth of different tumor types. Here, we
      show that metformin exerts antiproliferative effects on melanoma cells, whereas
      normal human melanocytes are resistant to these metformin-induced effects. To
      better understand the basis of this antiproliferative effect of metformin in
      melanoma, we characterized the sequence of events underlying metformin action. We
      showed that 24 h metformin treatment induced a cell cycle arrest in G0/G1 phases,
      while after 72 h, melanoma cells underwent autophagy as demonstrated by electron
      microscopy, immunochemistry, and by quantification of the autolysosome-associated
      LC3 and Beclin1 proteins. In addition, 96 h post metformin treatment we observed
      robust apoptosis of melanoma cells. Interestingly, inhibition of autophagy by
      knocking down LC3 or ATG5 decreased the extent of apoptosis, and suppressed the
      antiproliferative effect of metformin on melanoma cells, suggesting that
      apoptosis is a consequence of autophagy. The relevance of these observations were
      confirmed in vivo, as we showed that metformin treatment impaired the melanoma
      tumor growth in mice, and induced autophagy and apoptosis markers. Taken
      together, our data suggest that metformin has an important impact on melanoma
      growth, and may therefore be beneficial in patients with melanoma.

PMID- 21881602
TI  - Distribution of CD133 reveals glioma stem cells self-renew through symmetric and
      asymmetric cell divisions.
AB  - Malignant gliomas contain a population of self-renewing tumorigenic stem-like
      cells; however, it remains unclear how these glioma stem cells (GSCs) self-renew
      or generate cellular diversity at the single-cell level. Asymmetric cell division
      is a proposed mechanism to maintain cancer stem cells, yet the modes of cell
      division that GSCs utilize remain undetermined. Here, we used single-cell
      analyses to evaluate the cell division behavior of GSCs. Lineage-tracing analysis
      revealed that the majority of GSCs were generated through expansive symmetric
      cell division and not through asymmetric cell division. The majority of
      differentiated progeny was generated through symmetric pro-commitment divisions
      under expansion conditions and in the absence of growth factors, occurred mainly
      through asymmetric cell divisions. Mitotic pair analysis detected asymmetric
      CD133 segregation and not any other GSC marker in a fraction of mitoses, some of
      which were associated with Numb asymmetry. Under growth factor withdrawal
      conditions, the proportion of asymmetric CD133 divisions increased, congruent
      with the increase in asymmetric cell divisions observed in the lineage-tracing
      studies. Using single-cell-based observation, we provide definitive evidence that
      GSCs are capable of different modes of cell division and that the generation of
      cellular diversity occurs mainly through symmetric cell division, not through
      asymmetric cell division.

PMID- 21881603
TI  - Tolerance to drug-induced cell death favours the acquisition of multidrug
      resistance in Leishmania.
AB  - The control of the protozoan parasite Leishmania relies on few drugs with unknown
      cellular targets and unclear mode of action. Several antileishmanials, however,
      were shown to induce apoptosis in Leishmania and this death mechanism was further
      studied in drug-sensitive and drug-resistant Leishmania infantum. In sensitive
      parasites, antimonials (SbIII), miltefosine (MF) and amphotericin B (AMB), but
      not paromomycin (PARO), triggered apoptotic cell death associated with reactive
      oxygen species (ROS). In contrast, Leishmania mutants resistant to SbIII, MF or
      AMB not only failed to undergo apoptosis following exposure to their respective
      drugs, but also were more tolerant towards apoptosis induced by other
      antileishmanials, provided that these killed Leishmania via ROS production. Such
      tolerance favored the rapid acquisition of multidrug resistance. PARO killed
      Leishmania in a non-apoptotic manner and failed to produce ROS. PARO resistance
      neither protected against drug-induced apoptosis nor provided an increased rate
      of acquisition of resistance to other antileishmanials. However, the PARO
      resistant mutant, but not SbIII-, MF- or AMB-resistant mutants, became rapidly
      cross-resistant to methotrexate, a model drug also not producing ROS. Our results
      therefore link the mode of killing of drugs to tolerance to cell death and to a
      facilitated emergence of multidrug resistance. These findings may have
      fundamental implications in the field of chemotherapeutic interventions.

PMID- 21881604
TI  - Cell death in disease: from 2010 onwards.
AB  - The strong interest in cell death, and the shift in emphasis from basic
      mechanisms to translational aspects fostered the launch last year of the new
      sister journal of Cell Death and Differentiation, named Cell Death and Disease,
      to reflect its stronger focus towards clinical applications. Here, we review that
      first year of activity, which reflects an enthusiastic response by the scientific
      community. On the basis of this, we now launch two novel initiatives, the start
      of a new section dedicated to cancer metabolism and the opening of a new
      editorial office in Shanghai.

PMID- 21881606
TI  - Roles of the Polycomb group proteins in stem cells and cancer.
AB  - Polycomb group proteins have long been linked to the occurrence of different
      forms of cancer. Polycomb proteins form at least two distinct complexes, the
      Polycomb-repressive complexes 1 and 2 (PRC1 and PRC2). Some of the PRC complex
      subunits have been found to be overexpressed in a variety of different tumors.
      Epigenetic perturbations are likely to be the cause for transcriptional
      misregulation of tumor suppressor genes and of certain cell fates. It is
      especially critical for stem cells that their potential to self-renewal and to
      differentiate is tightly controlled and properly orchestrated. Misregulation of
      Polycomb protein levels often leads to either a block or unscheduled activation
      of developmental pathways, thereby enhancing the proliferation capability of a
      cell. The consequences of this misregulation have been linked to the
      establishment of cancer stem cells, which can produce tumors through a
      combination of increased self-renewal and the lack of complete cellular
      differentiation. Cancer stem cells are believed to persist within tumors and to
      elicit relapse and metastasis. In this review, we recapitulate the roles of
      Polycomb proteins in stem cell biology, and the impact their misregulation can
      have on cancer.

PMID- 21881605
TI  - Targeting neonatal ischemic brain injury with a pentapeptide-based irreversible
      caspase inhibitor.
AB  - Brain protection of the newborn remains a challenging priority and represents a
      totally unmet medical need. Pharmacological inhibition of caspases appears as a
      promising strategy for neuroprotection. In a translational perspective, we have
      developed a pentapeptide-based group II caspase inhibitor, TRP601/ORPHA133563,
      which reaches the brain, and inhibits caspases activation, mitochondrial release
      of cytochrome c, and apoptosis in vivo. Single administration of TRP601 protects
      newborn rodent brain against excitotoxicity, hypoxia-ischemia, and perinatal
      arterial stroke with a 6-h therapeutic time window, and has no adverse effects on
      physiological parameters. Safety pharmacology investigations, and toxicology
      studies in rodent and canine neonates, suggest that TRP601 is a lead compound for
      further drug development to treat ischemic brain damage in human newborns.

PMID- 21881607
TI  - Generation and characterization of antibodies specific for caspase-cleaved neo
      epitopes: a novel approach.
AB  - Apoptosis research has been significantly aided by the generation of antibodies
      against caspase-cleaved peptide neo-epitopes. However, most of these antibodies
      recognize the N-terminal fragment and are specific for the protein in question.
      The aim of this project was to create antibodies, which could identify caspase
      cleaved proteins without a priori knowledge of the cleavage sites or even the
      proteins themselves. We hypothesized that many caspase-cleavage products might
      have a common antigenic shape, given that they must all fit into the same active
      site of caspases. Rabbits were immunized with the eight most prevalent exposed C
      terminal tetrapeptide sequences following caspase cleavage. After purification of
      the antibodies we demonstrated (1) their specificity for exposed C-terminal (but
      not internal) peptides, (2) their ability to detect known caspase-cleaved
      proteins from apoptotic cell lysates or supernatants from apoptotic cell culture
      and (3) their ability to detect a caspase-cleaved protein whose tetrapeptide
      sequence differs from the eight tetrapeptides used to generate the antibodies.
      These antibodies have the potential to identify novel neo-epitopes produced by
      caspase cleavage and so can be used to identify pathway-specific caspase cleavage
      events in a specific cell type. Additionally this methodology may be applied to
      generate antibodies against products of other proteases, which have a well
      defined and non-promiscuous cleavage activity.

PMID- 21881609
TI  - Nocturnal emissions.

PMID- 21881610
TI  - Adaptation, redundancy or resilience.

PMID- 21881611
TI  - The incredible shrinking organelle.

PMID- 21881612
TI  - The great regulator. Basic research into the roles of RNA is steaming ahead, but
      its commercial exploitation has stalled.

PMID- 21881613
TI  - Testing time for telomeres. Telomere length can tell us something about disease
      susceptibility and ageing, but are commercial tests ready for prime time?

PMID- 21881614
TI  - What the UK public believes causes obesity, and what they want to do about it: a
      cross-sectional study.
AB  - Increases in the prevalence of obesity have led to calls for policy interventions
      in the United Kingdom. Little is known, however, about how the public explains
      overweight, or their support for interventions. Our research team recruited 500
      adults (>=18 years of age) across the United Kingdom to complete a cross
      sectional survey asking about beliefs concerning the causes of excess weight, and
      support for particular policy interventions. Respondents completed questionnaires
      in their homes with the assistance of an interviewer. Results suggested that
      support for policy interventions was greatest when responsibility was attributed
      to factors beyond individual control, with support for child-focused
      interventions particularly high. The relationship is more complex than previous
      studies suggest, as believing in the over-availability of unhealthy foods
      predicted higher support for policy interventions, whereas beliefs in structural
      explanations, such as cost, had little influence on support. Recognition of this
      complexity may help to design more effective future policies to tackle obesity.

PMID- 21881615
TI  - Black reefs: iron-induced phase shifts on coral reefs.
AB  - The Line Islands are calcium carbonate coral reef platforms located in iron-poor
      regions of the central Pacific. Natural terrestrial run-off of iron is non
      existent and aerial deposition is extremely low. However, a number of ship
      groundings have occurred on these atolls. The reefs surrounding the shipwreck
      debris are characterized by high benthic cover of turf algae, macroalgae,
      cyanobacterial mats and corallimorphs, as well as particulate-laden, cloudy
      water. These sites also have very low coral and crustose coralline algal cover
      and are call black reefs because of the dark-colored benthic community and
      reduced clarity of the overlying water column. Here we use a combination of
      benthic surveys, chemistry, metagenomics and microcosms to investigate if and how
      shipwrecks initiate and maintain black reefs. Comparative surveys show that the
      live coral cover was reduced from 40 to 60% to <10% on black reefs on Millennium,
      Tabuaeran and Kingman. These three sites are relatively large (>0.75 km(2)). The
      phase shift occurs rapidly; the Kingman black reef formed within 3 years of the
      ship grounding. Iron concentrations in algae tissue from the Millennium black
      reef site were six times higher than in algae collected from reference sites.
      Metagenomic sequencing of the Millennium Atoll black reef-associated microbial
      community was enriched in iron-associated virulence genes and known pathogens.
      Microcosm experiments showed that corals were killed by black reef rubble through
      microbial activity. Together these results demonstrate that shipwrecks and their
      associated iron pose significant threats to coral reefs in iron-limited regions.

PMID- 21881616
TI  - Coherent dynamics and association networks among lake bacterioplankton taxa.
AB  - Bacteria have important roles in freshwater food webs and in the cycling of
      elements in the ecosystem. Yet specific ecological features of individual
      phylogenetic groups and interactions among these are largely unknown. We used 454
      pyrosequencing of 16S rRNA genes to study associations of different
      bacterioplankton groups to environmental characteristics and their co-occurrence
      patterns over an annual cycle in a dimictic lake. Clear seasonal succession of
      the bacterioplankton community was observed. After binning of sequences into
      previously described and highly resolved phylogenetic groups (tribes), their
      temporal dynamics revealed extensive synchrony and associations with seasonal
      events such as ice coverage, ice-off, mixing and phytoplankton blooms. Coupling
      between closely and distantly related tribes was resolved by time-dependent rank
      correlations, suggesting ecological coherence that was often dependent on
      taxonomic relatedness. Association networks with the abundant freshwater
      Actinobacteria and Proteobacteria in focus revealed complex interdependencies
      within bacterioplankton communities and contrasting linkages to environmental
      conditions. Accordingly, unique ecological features can be inferred for each
      tribe and reveal the natural history of abundant cultured and uncultured
      freshwater bacteria.

PMID- 21881618
TI  - Divergence with age in blood pressure in African-Caribbean and white populations
      in England: implications for screening for hypertension.
AB  - BACKGROUND: We assessed when blood pressure (BP) and hypertension begin to rise
      in African-Caribbeans compared to the white population; and whether the change
      relates to body mass index (BMI). METHODS: Secondary analysis of the cross
      sectional Health Surveys for England among 22,723 participants (21,344 whites and
      1,379 African-Caribbeans) adults aged >=18 years. RESULTS: The cubic spline
      graphs showed a crossover (African-Caribbean greater than whites) at 30-40 years
      in BP. Age-specific mean BP and hypertension prevalence data showed at 20-29
      years African-Caribbean men were advantaged but not thereafter. There was little
      difference in BMI in men. African-Caribbean women had lower systolic BP (but
      higher prevalence of hypertension) at 20-29 years but higher BP and prevalence of
      hypertension thereafter. African-Caribbean women had higher BMI than white women.
      Regression showed an age and ethnicity interaction for systolic (0.076 mm Hg
      greater increase per year, P = 0.054) and diastolic BP (0.068 mm Hg greater
      increase per year (P = 0.009) and hypertension (OR equals 1.02, P = 0.004) in
      African-Caribbean men, and diastolic BP in African-Caribbean women (0.057 mm Hg
      greater increase per year, P = 0.017). Crossover was 28, 44, and 28 years for
      systolic BP, diastolic BP and hypertension in men, respectively; and 40 years for
      diastolic BP in women. CONCLUSIONS: Clinicians should be extra vigilant about
      screening African-Caribbean patients from the age of 30 years. Detailed study is
      needed to understand the still mysterious mechanisms for this crossover.

PMID- 21881617
TI  - Sustainable syntrophic growth of Dehalococcoides ethenogenes strain 195 with
      Desulfovibrio vulgaris Hildenborough and Methanobacterium congolense: global
      transcriptomic and proteomic analyses.
AB  - Dehalococcoides ethenogenes strain 195 (DE195) was grown in a sustainable
      syntrophic association with Desulfovibrio vulgaris Hildenborough (DVH) as a co
      culture, as well as with DVH and the hydrogenotrophic methanogen Methanobacterium
      congolense (MC) as a tri-culture using lactate as the sole energy and carbon
      source. In the co- and tri-cultures, maximum dechlorination rates of DE195 were
      enhanced by approximately three times (11.0+/-0.01 MUmol per day for the co
      culture and 10.1+/-0.3 MUmol per day for the tri-culture) compared with DE195
      grown alone (3.8+/-0.1 MUmol per day). Cell yield of DE195 was enhanced in the co
      culture (9.0+/-0.5 * 10(7) cells per MUmol Cl(-) released, compared with 6.8+/
      0.9 * 10(7) cells per MUmol Cl(-) released for the pure culture), whereas no
      further enhancement was observed in the tri-culture (7.3+/-1.8 * 10(7) cells per
      MUmol Cl(-) released). The transcriptome of DE195 grown in the co-culture was
      analyzed using a whole-genome microarray targeting DE195, which detected 102
      significantly up- or down-regulated genes compared with DE195 grown in isolation,
      whereas no significant transcriptomic difference was observed between co- and tri
      cultures. Proteomic analysis showed that 120 proteins were differentially
      expressed in the co-culture compared with DE195 grown in isolation.
      Physiological, transcriptomic and proteomic results indicate that the robust
      growth of DE195 in co- and tri-cultures is because of the advantages associated
      with the capabilities of DVH to ferment lactate to provide H(2) and acetate for
      growth, along with potential benefits from proton translocation, cobalamin
      salvaging and amino acid biosynthesis, whereas MC in the tri-culture provided no
      significant additional benefits beyond those of DVH.

PMID- 21881619
TI  - General and central obesity, combined oral contraceptive use and hypertension in
      Chinese women.
AB  - BACKGROUND: Asians have different body fat distributions and disease
      characteristics compared with Caucasians. The purpose of this study was to
      evaluate general and central obesity, combined oral contraceptive (COC) use, and
      their joint effects on the risk of hypertension in Chinese women. METHODS: A case
      control study including 1,760 women (878 hypertensive cases and 882 normotensive
      controls) was conducted in China. Body weight, height, waist circumference (WC),
      blood pressure, serum lipids, and apolipoproteins were measured. History of
      contraceptive use and relevant factors were investigated. Odds ratio (OR) with
      95% confidence interval (CI) was estimated for hypertension-related factors under
      unconditional logistic regression model. RESULTS: Our study showed that increased
      body mass index (BMI), increased WC, and COC use were risk factors for
      hypertension with an OR (95% CI) of 2.19 (1.69-2.83), 1.46 (1.13-1.88), and 1.26
      (1.02-1.56), respectively. Compared with WC, BMI was more strongly associated
      with hypertension risk (OR 3.40, 95% CI 2.28-5.05, for highest vs. lowest
      quartile) and was a better predictor for blood pressure. COC users had a 1.39
      fold (OR 1.39, 95% CI 1.14-1.69) increased risk compared with the nonusers, while
      stopping COC was associated with a 36% reduced risk (OR 0.64, 95% CI 0.42-0.98).
      The risk increased dramatically in combination of COC use with a BMI >=28 kg/m(2)
      or WC >=90 cm (OR 8.02, 95% CI 5.05-12.74; OR 5.76, 95% CI 3.65-9.12,
      respectively). CONCLUSIONS: General and central obesity, COC use, and their joint
      effects significantly increased the risk of hypertension in Chinese women.

PMID- 21881620
TI  - Role of the gut in visceral fat inflammation and metabolic disorders.

PMID- 21881621
TI  - Expanding the Scope of Biocatalysis: Oxidative Biotransformations on Solid
      Supported Substrates.
AB  - Oxidative biocatalytic reactions were performed on solid-supported substrates,
      thus expanding the repertoire of biotransformations that can be carried out on
      the solid phase. Various phenylacetic and benzoic acid analogs were attached to
      controlled pore glass beads via an enzyme-cleavable linker. Reactions catalyzed
      by peroxidases (soybean and chloro), tyrosinase, and alcohol
      oxidase/dehydrogenase gave a range of products, including oligophenols,
      halogenated aromatics, catechols, and aryl aldehydes. The resulting products were
      recovered following cleavage from the beads using alpha-chymotrypsin to
      selectively hydrolyze a chemically non-labile amide linkage. Controlled pore
      glass (CPG) modified with a polyethylene glycol (PEG) linker afforded
      substantially higher product yields than non-PEGylated CPG or non-swellable
      polymeric resins. This work represents the first attempt to combine solid-phase
      oxidative biotransformations with subsequent protease-catalyzed cleavage, and
      serves to further expand the use of biocatalysis in synthetic and medicinal
      chemistry.

PMID- 21881622
TI  - Time-reversal Techniques in Ultrasound-assisted Convection-enhanced Drug Delivery
      to the Brain: Technology Development and In Vivo Evaluation.
AB  - We describe a drug delivery method that combines Time-Reversal Acoustics (TRA)
      with Convection-Enhanced Delivery (CED) to improve the delivery of therapeutics
      to the interstitium of the brain. The Ultrasound-assisted CED approach (UCED)
      circumvents the blood-brain barrier by infusing compounds through a cannula that
      is inserted into the brain while simultaneously delivering ultrasound to improve
      the penetration of pharmaceuticals. CED without ultrasound-assistance has been
      used to treat a variety of neural disorders, including glioblastoma multiforme, a
      malignancy that presents a very poor prognosis for patients. We describe a novel
      system that is used to infuse fluids into the brain parenchyma while
      simultaneously exposing the tissue to safe levels of 1-MHz, low intensity,
      ultrasound energy. The system includes a combined infusion needle-hydrophone, a
      10-channel ultralow-output impedance amplifier, a broad-band ultrasound
      resonator, and MatLab(r)-based TRA control and user-interface. TRA allows easy
      coupling of ultrasound therapy through the skull without complex phase-correction
      and array design. The smart targeting UCED system has been tested in vivo and
      results show it provides 1.5-mm spatial resolution for UCED and improves tracer
      distribution in the brain over CED alone.

PMID- 21881628
TI  - Computational and spectroscopic studies of organic mixed-valence compounds: where
      is the charge?
AB  - This article discusses recent progress by a combination of spectroscopy and
      quantum-chemical calculations in classifying and characterizing organic mixed
      valence systems in terms of their localized vs. delocalized character. A recently
      developed quantum-chemical protocol based on non-standard hybrid functionals and
      continuum solvent models is evaluated for an extended set of mixed-valence bis
      triarylamine radical cations, augmented by unsymmetrical neutral triarylamine
      perchlorotriphenylmethyl radicals. It turns out that the protocol is able to
      provide a successful assignment to class II or class III Robin-Day behavior and
      gives quite accurate ground- and excited-state properties for the radical
      cations. The limits of the protocol are probed by the anthracene-bridged system
      8, where it is suspected that specific solute-solvent interactions are important
      and not covered by the continuum solvent model. Intervalence charge-transfer
      excitation energies for the neutral unsymmetrical radicals are systematically
      overestimated, but dipole moments and a number of other properties are obtained
      accurately by the protocol.

PMID- 21881623
TI  - Detailed Analysis for the Solvolysis of Isopropenyl Chloroformate.
AB  - The specific rates of solvolysis (including those obtained from the literature)
      of isopropenyl chloroformate (1) are analyzed using the extended Grunwald
      Winstein equation, involving the N(T) scale of solvent nucleophilicity (S
      methyldibenzothiophenium ion) combined with a Y(Cl) scale based on 1-adamantyl
      chloride solvolysis. A similarity model approach, using phenyl chloroformate
      solvolyses for comparison, indicated a dominant bimolecular carbonyl-addition
      mechanism for the solvolyses of 1 in all solvents except 97% 1,1,1,3,3,3
      hexafluoro-2-propanol (HFIP). An extensive evaluation of the outcomes acquired
      through the application of the extended Grunwald-Winstein equation resulted in
      the proposal of an addition-elimination mechanism dominating in most of the
      solvents, but in 97-70% HFIP, and 97% 2,2,2-trifluoroethanol (TFE), it is
      proposed that a superimposed unimolecular (S(N)1) type ionization is making a
      significant contribution.

PMID- 21881629
TI  - Dynamic electro-chemo-mechanical analysis during cyclic voltammetry.
AB  - We report and validate a method for measuring the strain-response, sigma, of the
      electrode potential of electrically conductive solids in a fluid electrolyte.
      Simultaneously with cyclic voltammetry, the electrode is subjected to cyclic
      elastic strain at frequencies of up to 100 Hz. We explore three independent
      strategies for separating the cyclic variation of potential or current from the
      voltammogram proper, and find that the results of all three are in quantitative
      agreement. By means of an example we explore dominantly capacitive processes at a
      gold electrode in H(2)SO(4) and HClO(4). The response parameter sigma is not
      sensitive to the nature of the electrolyte. Yet, its value varies by more than a
      factor of two in the potential interval investigated. The potential of largest
      magnitude of sigma agrees closely with the potential of zero charge.

PMID- 21881630
TI  - Kinetics of electron recombination of dye-sensitized solar cells based on TiO2
      nanorod arrays sensitized with different dyes.
AB  - The performance and electron recombination kinetics of dye-sensitized solar cells
      based on TiO(2) films consisting of one-dimensional nanorod arrays (NR-DSSCs)
      which are sensitized with dyes N719, C218 and D205, respectively, have been
      studied. It has been found that the best efficiency is obtained with the dye C218
      based NR-DSSCs, benefiting from a 40% higher short-circuit photocurrent density.
      However, the open circuit photovoltage of the N719 based cell is 40 mV higher
      than that of the organic dye C218 and D205 based devices. Investigation of the
      electron recombination kinetics of the NR-DSSCs has revealed that the effective
      electron lifetime, tau(n), of the different dye based NR-DSSCs shows the sequence
      of C218 > D205 > N719. The higher V(oc) with the N719 based NR-DSSC is originated
      from the more negative energy level of the conduction band of the TiO(2) film. In
      addition, in comparison to the DSSCs with the conventional nanocrystalline
      particles based TiO(2) films, the NR-DSSCs have shown over two orders of
      magnitude higher tau(n) when employing N719 as the sensitizer. Nevertheless, the
      tau(n) of the DSSCs with the C218 based nanorod arrays is only ten-fold higher
      than that of the nanoparticles based devices. The remarkable characteristic of
      the dye C218 in suppressing the electron recombination of DSSCs is discussed.

PMID- 21881631
TI  - Niobium phosphates as new highly selective catalysts for the oxidative
      dehydrogenation of ethane.
AB  - Several niobium phosphate phases have been prepared, fully characterized and
      tested as catalysts for the selective oxidation of ethane to ethylene. Three
      distinct niobium phosphate catalysts were prepared, and each was comprised
      predominantly of a different bulk phase, namely Nb(2)P(4)O(15), NbOPO(4) and
      Nb(1.91)P(2.82)O(12). All of the niobium phosphate catalysts showed high
      selectivity towards ethylene, but the best catalyst was Nb(1.91)P(2.82)O(12),
      which was produced from the reduction of niobium oxide phosphate (NbOPO(4)) by
      hydrogen. It was particularly selective for ethylene, giving ca. 95% selectivity
      at 5% conversion, decreasing to ca. 90% at 15% conversion, and only produced low
      levels of carbon oxides. It was also determined that the only primary product
      from ethane oxidation over this catalyst was ethylene. Catalyst activity also
      increased with time-on-line, and this behaviour was ascribed to an increase of
      the concentration of the Nb(1.91)P(2.82)O(12) phase, as partially transformed
      NbOPO(4), formed during preparation, was converted to Nb(1.91)P(2.82)O(12) during
      use. Catalysts with predominant phases of Nb(2)P(4)O(15) and NbOPO(4) also showed
      appreciable activity and selectivities to ethylene with values around 75% and 85%
      respectively at 5% ethane conversion. The presence of phosphorous is required to
      achieve high ethylene selectivity, as orthorhombic and monoclinic Nb(2)O(5)
      catalysts showed similar activity, but displayed selectivities to ethylene that
      were <20% under the same reaction conditions. To the best of our knowledge, this
      is the first time that niobium phosphates have been shown to be highly selective
      catalysts for the oxidation of ethane to ethylene, and demonstrates that they are
      worthy candidates for further study.

PMID- 21881637
TI  - Modulation of self-assembly and magnetism of Cu(II) grids in solution.
AB  - Depending on the Cu(II)/ligand molar ratio, a pyrimidine-based ligand generates a
      tetranuclear grid (1/1) or a dinuclear stick (2/1). EPR, MS and visible
      spectroscopy studies suggest that dilution produces partial dissociation of the
      grid in solution. Replacement of 2-H-pyrimidine by a 2-phenyl-triazine unit
      prevents the dissociation of the grid. All these factors influence the magnetic
      properties of the architectures herein involved.

PMID- 21881638
TI  - Investigation of a fiber optic surface plasmon spectroscopy in conjunction with
      conductivity as an in situ method for simultaneously monitoring changes in
      dissolved organic carbon and salinity in coastal waters.
AB  - A combination surface plasmon resonance (SPR) and conductivity sensor array was
      developed and implemented to demonstrate the ability to differentiate among
      changes in dissolved organic carbon (DOC) and salinity in coastal water. The
      array is capable of achieving sufficient spatial and temporal data density to
      better understand the cycling and fate of terrestrial DOC in coastal areas. DOC
      is the second largest source of bioreactive carbon in the environment and plays a
      key role in mediating microbial activity and generation of atmospheric CO(2). In
      the coastal areas, the salinity is also an important property in many
      applications, such as leak detection for landfill liners, saltwater intrusion to
      drinking water, marine environment monitoring, and seasonal climate prediction.
      Conductivity sensors are the industry standard for determining salinity in ocean
      systems. However, both conductivity and refractive index sensors, such as SPR
      spectroscopy based sensors, respond to salinity and DOC levels. To demonstrate
      the capability of the SPR sensor and a conductivity sensor to collect
      complimentary data useful in discrimination of salinity and DOC in coastal zone
      water, conductivity, SPR, and temperature data were collected during passage from
      the Juan de Fuca ridge area returning to the University of Washington docks.

PMID- 21881639
TI  - Selective separation of structure-related alkaloids in Rhizoma coptidis with
      "click" binaphthyl stationary phase and their structural elucidation with liquid
      chromatography-mass spectrometry.
AB  - It is a new task to separate structure-related compounds into a fraction
      according to their structural characteristics in a complex traditional Chinese
      medicine (TCM). This method makes separation of the components of the sample
      simple and structural elucidation easy. In this study, selective separation of
      alkaloids in Rhizoma coptidis was realized on a "click" binaphthyl column
      possessing a planar conjugate structure. Three kinds of alkaloids, aporphine,
      tetrahydroprotoberberine and protoberberine in Rhizoma coptidis showed better
      retention than other compounds by virtue of pi-pi interactions with the
      stationary phase. Moreover, the "click" binaphthyl column could distinguish the
      aporphine and tetrahydroprotoberberine alkaloids possessing two benzene rings
      from the protoberberine alkaloids possessing three benzene rings. After
      separating on the "click" binaphthyl column, the fractions containing the
      alkaloids were collected and then analyzed with liquid chromatography-mass
      spectrometry (LC-MS). Totally, 23 alkaloids were identified, and among these
      alkaloids, three tetrahydroprotoberberine, two aporphine and seven protoberberine
      alkaloids were first found in Rhizoma coptidis. These newly found alkaloids are
      minor compounds, and they are always neglected without eliminating the
      interference of compounds in large amounts by pre-separation on the "click"
      binaphthyl column. The typical fragmentation pathways of each class of alkaloids
      were summarized to illustrate their structures. In the MS(2) spectrum, the loss
      of a molecule of dimethylamine ((CH(3))(2)NH) was observed as the characteristic
      loss of aporphine alkaloids. All the tetrahydroprotoberberine alkaloids would
      undergo the Retro-Diels-Alder (RDA) fragmentation reaction in the MS(2)
      fragmentation. For protoberberine alkaloids, different characteristic
      fragmentations were observed with different skeleton structures.

PMID- 21881640
TI  - Electrodeposition of unsubstituted iron phthalocyanine nano-structure film in a
      functionalized ionic liquid and its electrocatalytic and electroanalysis
      applications.
AB  - We report a novel and facile electrodeposition method to fabricate a nano
      structure film of the unsubstituted metal phthalocyanine on a glassy carbon
      electrode (GCE). In this electrodeposition system, unsubstituted iron(II)
      phthalocyanine (u-FePc) was chosen as the model complex of the unsubstituted
      metalphthalocyanine, and the ionic liquid 1-octyl-3-methylimidazolium
      trifluoroacetate was employed as the solvent and electrolyte, thus avoiding the
      use of additional costly supporting electrolyte. Excellent electrocatalytic
      performance of the u-FePc nano-structure film was first evaluated by
      electrocatalytic oxidation of ascorbic acid (AA). Compared with the bare GCE, the
      oxidation peak potential of AA at u-FePc/GCE shifted negatively about 264 mV, and
      the oxidation peak current increased about 1.8 times. Furthermore, the as
      prepared film was employed for the investigation of luminol
      electrochemiluminescence (ECL) behavior in neutral solution, which showed
      excellent performance including under selected experimental conditions, the ECL
      intensity showing an acceptable linear relationship for luminol concentrations
      between 5 * 10(-8) and 5 * 10(-6) M, and a linear response to H(2)O(2) over a
      wide concentration range, from 1.0 * 10(-8) to 1.0 * 10(-5) M in 3.0 MUM luminol
      solution.

PMID- 21881642
TI  - Expedient entry to the piperazinohydroisoquinoline ring system using a sequential
      Ugi/Pictet-Spengler/reductive methylation reaction protocol.
AB  - An expedient entry to the piperazinohydroisoquinoline ring system present in the
      tetrahydroisoquinoline antitumor alkaloids family is described. The synthetic
      sequence involves: a sequential Ugi reaction followed by an N-Boc-deprotection
      process and iminium formation with a spontaneous Pictet-Spengler cyclization and
      reductive N-methylation, with all these processes performed in a two-operation
      protocol in the same reaction flask.

PMID- 21881641
TI  - Hemin/G-quadruplexes as DNAzymes for the fluorescent detection of DNA, aptamer
      thrombin complexes, and probing the activity of glucose oxidase.
AB  - Hemin/G-quadruplex catalyzes the H(2)O(2)-mediated oxidation of Amplex Red to the
      fluorescent product resorufin. This process is implemented to develop hairpin
      nucleic acid structures for the detection of DNA, to probe the catalytic activity
      of glucose oxidase, to use the thrombin-aptamer complex as a catalytic readout
      structure, and to quantitatively analyze telomere chain composition.

PMID- 21881643
TI  - Versatile grafting approaches to star-shaped POSS-containing hybrid polymers
      using RAFT polymerization and click chemistry.
AB  - An alkyne-bearing polyhedral oligomeric silsesquioxane (POSS) core was used to
      prepare POSS-containing polymer hybrids using 'grafting to' or 'grafting from'
      strategies in combination with reversible chain transfer and click chemistry.

PMID- 21881644
TI  - Effect of oxygen evolution catalysts on hematite nanorods for solar water
      oxidation.
AB  - Photochemical deposition of Co and Ni based oxygen evolution catalysts on
      hematite nanorods cathodically shifted the onset potential of photocurrent near
      to the flat band potential of hematite. A 9.5 fold enhancement in the
      photocurrent density at 0.86 V vs. RHE compared to the parent hematite photoanode
      was observed with the Ni-Bi/Fe(2)O(3) photoanode.

PMID- 21881646
TI  - One-pot synthesis of cyclopentadienyl endcapped poly(2-ethyl-2-oxazoline) and
      subsequent ambient temperature Diels-Alder conjugations.
AB  - An efficient method for the preparation of cyclopentadienyl endcapped poly(2
      ethyl-2-oxazoline) (PEtOx-Cp) via cationic ring-opening polymerization utilizing
      sodium cyclopentadienide as a termination agent is presented. Subsequent Diels
      Alder reactions with N-substituted maleimides proceed quantitatively at ambient
      temperature. A block copolymer (PEtOx-b-PEG) is prepared employing maleimide
      terminated poly(ethylene glycol).

PMID- 21881645
TI  - Solubilization of pristine fullerene by the unfolding mechanism of bovine serum
      albumin for cytotoxic application.
AB  - A method for solubilization of pristine fullerene (C(60)) in water was proposed
      by directly using bovine serum albumin (BSA) as a "solubilizer" by means of the
      unfolding mechanism. C(60) aqueous solution with a small distribution size,
      excellent dispersion stability and high dispersion concentration was obtained
      without the use of derivatization and organic solvent.

PMID- 21881647
TI  - Pentametallic lanthanide-alkoxide square-based pyramids: high energy barrier for
      thermal relaxation in a holmium single molecule magnet.
AB  - Pentametallic Ln complexes of formula [Ln(5)O(O(i)Pr)(13)] have been made, where
      Ln(III) = Sm, Gd, Tb, Ho and Er; slow magnetisation relaxation to 33 K is
      observed for the Ho complex with an energy barrier of ca. 400 K.

PMID- 21881648
TI  - Synthesis of complexes bearing NH,NMe-substituted NHCs by oxidative addition of 2
      halogenato-N-methylbenzimidazoles to Ni(0).
AB  - Reaction of 2-X-N-methylbenzimidazole (X = chloro, iodo) with Ni(0) complexes in
      the presence of dppe or PEt(3) and an external proton source yielded via an
      oxidative addition reaction nickel(II) complexes bearing NH,NMe-functionalized
      NHC ligands.

PMID- 21881649
TI  - Structure and bonding in three-coordinate N-heterocyclic carbene adducts of
      iron(II) bis(trimethylsilyl)amide.
AB  - The molecular structures, chemical bonding and magnetochemistry of the three
      coordinate iron(II) NHC complexes [(NHC)Fe{N(SiMe(3))(2)}(2)] (NHC = IPr, 2; NHC
      = IMes, 3) are reported.

PMID- 21881650
TI  - Prediction of gas solubilities in ionic liquids.
AB  - Ionic liquids (of which it is estimated that there are at least one million
      simple fluids) generate a rich chemical space, which is now just at the beginning
      of its systematic exploration. Many properties of ionic liquids are truly unique
      and, which is more important, can be finely tuned. Differential solubility of
      industrial chemicals in ionic liquids is particularly interesting, because it can
      be a basis for novel, efficient, environmentally friendly technologies. Given the
      vast number of potential ionic liquids, and the impossibility of a comprehensive
      empirical exploration, it is essential to extract the maximum information from
      extant data. We report here some computational models of gas solubility. These
      multiple regression- and neural network-based models cover a chemical space
      spanned by 48 ionic liquids and 23 industrially important gases. Molecular
      polarisabilities and special Lewis acidity and basicity descriptors calculated
      for the ionic liquid cations and anions, as well as for the gaseous solutes, are
      used as input parameters. The quality of fit "observed versus predicted Henry's
      law constants" is particularly good for the neural network model. Validation was
      established with an external dataset, again with a high quality fit. In contrast
      to many other neural network models published, our model is no "black box", since
      contributions of the parameters and their nonlinearity characteristics are
      calculated and analysed.

PMID- 21881651
TI  - Generation of clean iron nanocrystals on an ultra-thin SiO(x) film on Si(001).
AB  - Upon exposure to Fe(CO)(5), the formation of pure cubic Fe nanocrystals with
      dimensions up to ~75 nm is reported on ultra-thin SiO(x) films (thickness ~ 0.5
      nm) on Si(001), which have been prepared in situ under UHV conditions. The active
      centers for initial decomposition of Fe(CO)(5) resulting in the growth of the Fe
      clusters are proposed to be SiO sites. After nucleation at these sites, further
      crystal growth is observed due to autocatalytic dissociation of Fe(CO)(5) at room
      temperature. The density of the Fe clusters can be increased by irradiating the
      surface with a focused electron beam (15 keV) prior to gas exposure. The
      formation of the active SiO sites upon electron irradiation is attributed to
      oxygen desorption via the Knotek-Feibelman mechanism.

PMID- 21881652
TI  - Differential diffusion effects on buoyancy-driven instabilities of acid-base
      fronts: the case of a color indicator.
AB  - Buoyancy-driven hydrodynamic instabilities of acid-base fronts are studied both
      experimentally and theoretically in the case where an aqueous solution of a
      strong acid is put above a denser aqueous solution of a color indicator in the
      gravity field. The neutralization reaction between the acid and the color
      indicator as well as their differential diffusion modifies the initially stable
      density profile in the system and can trigger convective motions both above and
      below the initial contact line. The type of patterns observed as well as their
      wavelength and the speed of the reaction front are shown to depend on the value
      of the initial concentrations of the acid and of the color indicator and on their
      ratio. A reaction-diffusion model based on charge balances and ion pair mobility
      explains how the instability scenarios change when the concentration of the
      reactants are varied.

PMID- 21881653
TI  - Predicting hydration Gibbs energies of alkyl-aromatics using molecular
      simulation: a comparison of current force fields and the development of a new
      parameter set for accurate solvation data.
AB  - The Gibbs energy of hydration is an important quantity to understand the
      molecular behavior in aqueous systems at constant temperature and pressure. In
      this work we review the performance of some popular force fields, namely TraPPE,
      OPLS-AA and Gromos, in reproducing the experimental Gibbs energies of hydration
      of several alkyl-aromatic compounds--benzene, mono-, di- and tri-substituted
      alkylbenzenes--using molecular simulation techniques. In the second part of the
      paper, we report a new model that is able to improve such hydration energy
      predictions, based on Lennard Jones parameters from the recent TraPPE-EH force
      field and atomic partial charges obtained from natural population analysis of
      density functional theory calculations. We apply a scaling factor determined by
      fitting the experimental hydration energy of only two solutes, and then present a
      simple rule to generate atomic partial charges for different substituted alkyl
      aromatics. This rule has the added advantages of eliminating the unnecessary
      assumption of fixed charge on every substituted carbon atom and providing a
      simple guideline for extrapolating the charge assignment to any multi-substituted
      alkyl-aromatic molecule. The point charges derived here yield excellent
      predictions of experimental Gibbs energies of hydration, with an overall absolute
      average deviation of less than 0.6 kJ mol(-1). This new parameter set can also
      give good predictive performance for other thermodynamic properties and liquid
      structural information.

PMID- 21881654
TI  - Coulomb explosion of nitrogen and oxygen molecules through non-Coulombic states.
AB  - We have systematically studied Coulomb explosion of nitrogen and oxygen molecules
      in intense 8 and 24 fs laser pulses. In the experiment, we explicitly separated
      all explosion pathways through coincident measurements. The high resolution
      kinetic energy releases (KERs) and the exotic angular distributions of atomic
      ions provide direct evidence that Coulomb explosion occurs through non-Coulombic
      states. In the theory, we calculated dissociation potential energy curves (PECs)
      of nitrogen and oxygen molecules and their multicharged molecular ions using
      multiconfiguration second-order perturbation theory. The results indicate that
      Coulomb potentials are close to the accurate PECs of multicharged molecular ions
      only when the internuclear distance is larger than 3 A. In comparison with the
      experimental observations and the theoretical calculations, we determined the
      internuclear distance when Coulombic explosion occurs. It is near the equilibrium
      distance of the neutral molecules in the case of 8 fs laser pulses and expands
      gradually with the increase of the charge state of the molecular ions in the case
      of 24 fs laser pulses.

PMID- 21881655
TI  - Computational characterization of zeolite porous networks: an automated approach.
AB  - An automated method has been developed to fully characterize the three
      dimensional structure of zeolite porous networks. The proposed optimization-based
      approach starts with the crystallographic coordinates of a structure and
      identifies all portals, channels, and cages in a unit cell, as well as their
      connectivity. We apply our algorithms to known zeolites, hypothetical zeolites,
      and zeolite-like structures and use the characterizations to calculate important
      quantities such as pore size distribution, accessible volume, surface area, and
      largest cavity and pore limiting diameters. We aggregate this data over many
      framework types to gain insights about zeolite selectivity. Finally, we develop a
      continuous-time Markov chain model to estimate the probability of occupancy of
      adsorption sites throughout the porous network. ZEOMICS, an online database of
      structure characterizations and web tool for the automated approach is freely
      available to the scientific community (http://helios.princeton.edu/zeomics/).

PMID- 21881656
TI  - Probing the interaction of amorphous solid water on a hydrophobic surface:
      dewetting and crystallization kinetics of ASW on carbon tetrachloride.
AB  - Desorption of carbon tetrachloride from beneath an amorphous solid water (ASW)
      overlayer is explored utilizing a combination of temperature programmed
      desorption and infrared spectroscopy. Otherwise inaccessible information about
      the dewetting and crystallization of ASW is revealed by monitoring desorption of
      the CCl(4) underlayer. The desorption maximum of CCl(4) on graphene occurs at
      ~140 K. When ASW wets the CCl(4) no desorption below 140 K is observed. However,
      the mobility of the water molecules increases with ASW deposition temperature,
      leading to a thermodynamically driven dewetting of water from the hydrophobic
      CCl(4) surface. This dewetting exposes some CCl(4) to the ambient environment,
      allowing unhindered desorption of CCl(4) below 140 K. When ASW completely covers
      the underlayer, desorption of CCl(4) is delayed until crystallization induced
      cracking of the ASW overlayer opens an escape path to the surface. The subsequent
      rapid episodic release of CCl(4) is termed a "molecular volcano". Reflection
      absorption infrared spectroscopy (RAIRS) measurements indicate that the onset and
      duration of the molecular volcano is directly controlled by the ASW
      crystallization kinetics.

PMID- 21881657
TI  - Excited-state calculations with TD-DFT: from benchmarks to simulations in complex
      environments.
AB  - In this perspective, we present an overview of recent progress on Time-Dependent
      Density Functional Theory (TD-DFT) with a specific focus on its accuracy and on
      models able to take into account environmental effects, including complex media.
      To this end, we first summarise recent benchmarks and define an average TD-DFT
      accuracy in reproducing excitation energies when a conventional approach is used.
      Next, coupling of TD-DFT with models able to account for different kinds of
      interactions between a central chromophore and nearby chemical objects (solvent,
      organic cage, metal as well as semi-conducting surface) is investigated. Examples
      of application to excitation properties are presented, allowing to briefly
      describe several recent computational strategies. In addition, an extension of TD
      DFT to describe a phenomenon involving interacting chromophores, e.g. the
      electronic energy transfer (EET), is presented to illustrate that this
      methodology can be applied to processes beyond the vertical excitation. This
      perspective therefore aims to provide to non-specialists a flavour of recent
      trends in the field of simulations of excited states in "realistic" situations.

PMID- 21881658
TI  - A protic ionic liquid attenuates the deleterious actions of urea on alpha
      chymotrypsin.
AB  - We present a biocompatible ionic liquid, triethyl ammonium acetate (TEAA), that
      attenuates the denaturation action of a non-ionic chaotrope, urea, on the
      industrially relevant proteolytic enzyme alpha-chymotrypsin.

PMID- 21881659
TI  - Slow photoelectron velocity-map imaging spectroscopy of the phenoxide and
      thiophenoxide anions.
AB  - High resolution anion photodetachment spectra of the phenoxide and thiophenoxide
      anions were obtained with slow electron velocity-map imaging. The spectra show
      transitions to the X(2)B(1) neutral states of both species and to the A(2)B(2)
      state of the thiophenoxy radical. Comparison of the spectra with Franck-Condon
      simulations allows several gas-phase vibrations to be assigned. The adiabatic
      electron affinities are determined to be 2.2538(8) eV and 2.3542(6) eV for
      phenoxy and thiophenoxy, respectively. The term energy of the A(2)B(2) state of
      thiophenoxy is found to be 0.3719(9) eV, higher than the values reported in
      photodissociation experiments of thiophenol.

PMID- 21881660
TI  - Intercalation synthesis of functional hybrid materials based on layered simple
      hydroxide hosts and ionic liquid guests--a pathway towards multifunctional
      ionogels without a silica matrix?
AB  - Functional hybrid materials on the basis of inorganic hosts and ionic liquids
      (ILs) as guests hold promise for a virtually unlimited number of applications. In
      particular, the interaction and the combination of properties of a defined
      inorganic matrix and a specific IL could lead to synergistic effects in property
      selection and tuning. Such hybrid materials, generally termed ionogels, are thus
      an emerging topic in hybrid materials research. The current article addresses
      some of the recent developments and focuses on the question why silica is
      currently the dominating matrix used for (inorganic) ionogel fabrication. In
      comparison to silica, matrix materials such as layered simple hydroxides, layered
      double hydroxides, clay-type substances, magnetic or catalytically active solids,
      and many other compounds could be much more interesting because they themselves
      may carry useful functionalities, which could also be exploited for
      multifunctional hybrid materials synthesis. The current article combines
      experimental results with some arguments as to how new, advanced functional
      hybrid materials can be generated and which obstacles will need to be overcome to
      successfully achieve the synthesis of a desired target material.

PMID- 21881661
TI  - Water-actuated microcapsules fabricated by microfluidics.
AB  - We found a new water-actuated feature of poly(N-isopropylacrylamide) microgels
      and fabricated microcapsules with this feature based on microfluidic double
      emulsions. The microcapsules would release encapsulated actives by simple
      hydration, while forming biphasic hybrid microparticles by gradual dehydration.
      More complex microcapsules and hybrid microparticles could be produced by varying
      flow rates and inner oil types. These novel microcapsules could potentially be
      used for controllable storage or release of chemicals, fabrication of complex
      microparticles and applications in biochemical fields.

PMID- 21881662
TI  - First-principles studies on structural and electronic properties of GaN-AlN
      heterostructure nanowires.
AB  - The structural and electronic properties of core-shell, eutectic, biaxial and
      superlattice GaN-AlN nanowires were studied through density functional theory
      computations. Due to more surface dangling bonds, nanowires with smaller
      diameters are energetically unfavorable. For the GaN-AlN heterostructure
      nanowires, their electronic properties highly depend on the GaN content, axial
      strain, configuration, and size. The valence bands are less affected by the GaN
      content, while the conduction bands depend on it. Hydrogen-passivated nanowires
      have much larger band gaps than their counterparts, since the surface states are
      removed by saturating the dangling bonds with hydrogen atoms. Moreover, due to
      multiple quantum-well structures, the confined electrons (holes) of superlattice
      nanowires become more localized and the difference of the mobility between the
      electron and hole becomes less apparent if the width of the barrier is larger.
      These findings are of value for better understanding heterostructure nanowires
      and their potential utilization.

PMID- 21881663
TI  - Dioxaborirane: a highly reactive peroxide that is the likely intermediate in
      borate catalysed electrophilic reactions of hydrogen peroxide in alkaline aqueous
      solution.
AB  - This paper reports on a kinetic and theoretical study into the borate mediated
      reaction of dimethyl sulfide with hydrogen peroxide in both acid and alkaline
      conditions. At high pH, whilst the kinetic data is consistent with the catalytic
      species being monoperoxoborate, formed from the rapid equilibrium between
      hydrogen peroxide and boric acid, DFT calculations show that this species is in
      fact less reactive than hydrogen peroxide, requiring us to seek an alternative
      catalytic mechanism. DFT provides an important insight for this, showing that
      although boric acid and peroxoboric acid are primarily Lewis acids, they can
      exhibit a small degree of Bronsted acidity, allowing, respectively, the
      B(O)(OH)(2)(-) and HOOB(OH)(O)(-) anions to exist in small concentrations. Whilst
      the peroxoborate anion, HOOB(OH)(O)(-), is predicted to have only marginal
      catalytic activity, its tautomer, dioxaborirane, (HO)(2)BO(2)(-), a three
      membered cyclic peroxide, has a very low activation barrier of 2.8 kcal/mol.
      Hence, even though dioxaborirane is likely to be present in very low
      concentrations, it is still sufficiently reactive for overall rate enhancements
      to be observed for this system. This is the first literature report of this
      species. The observed low selectivity observed for borate catalysed reactions of
      hydrogen peroxide with a range of substituted phenyl methyl sulfides in our
      previous study (D. M. Davies, M. E. Deary, K. Quill and R. A. Smith, Chem.-Eur.
      J. 2005, 11, 3552-3558) is further evidence in favour of a highly reactive
      catalytic species. At low pH, kinetic data shows that borate catalyses the
      reaction between hydrogen peroxide and dimethyl sulfide; this is supported by DFT
      calculations that predict peroxoboric acid to be an effective catalytic
      intermediate, with an energy barrier of 7.4 kcal mol(-1) compared to 10.1 kcal
      mol(-1) for the uncatalysed system. Nevertheless, the overall contribution of
      this pathway is small because of the unfavourable equilibrium between hydrogen
      peroxide and boric acid to form peroxoboric acid.

PMID- 21881664
TI  - Photoelectrochemical, photophysical and morphological studies of electrostatic
      layer-by-layer thin films based on poly(p-phenylenevinylene) and single-walled
      carbon nanotubes.
AB  - The preparation of multilayer films based on poly(p-phenylenevinylene) (PPV) and
      carboxylic-functionalized single-walled carbon nanotubes (SWNT-COOH) by
      electrostatic interaction using the layer-by-layer (LbL) deposition method is
      reported herein. The multilayer build-up, monitored by UV-Vis and
      photoluminescence (PL) spectroscopies, displayed a linear behavior with the
      number of PPV and SWNT-COOH layers deposited that undergo deviation and spectral
      changes for thicker films. Film morphology was evaluated by AFM and
      epifluorescence microscopies showing remarkable changes after incorporation of
      SWNT-COOH layers. Films without SWNT show roughness and present dispersed grains;
      films with SWNT-COOH layers are flatter and some carbon nanotube bundles can be
      visualized. The photoinduced charge transfer from the conducting polymer to SWNT
      COOH was analyzed by PL quenching either by the decrease of the emission
      intensity or by the presence of dark domains in the epifluorescence micrographs.
      Photoelectrochemical characterization was performed under white light and the
      films containing SWNT-COOH displayed photocurrent values between 2.0 MUA cm(-2)
      and 7.5 MUA cm(-2), as the amount of these materials increases in the film. No
      photocurrent was observed for the film without carbon nanotubes. Photocurrent
      generation was enhanced and became more stable when an intermediate layer of
      PEDOT:PSS was interposed between the active layer and the ITO electrode,
      indicating an improvement in hole transfer to the contacts. Our results indicate
      that these multilayer films are promising candidates as active layers for organic
      photovoltaic cells.

PMID- 21881665
TI  - Sensitivity improvement in laser ablation inductively coupled plasma mass
      spectrometry achieved using a methane/argon and methanol/water/argon mixed gas
      plasma.
AB  - The influence of the addition of carbon using methane or methanol/water to an
      inductively coupled plasma (ICP) via the carrier gas flow on the sensitivity in
      laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was
      studied. During the ablation of SRM NIST 610 with simultaneous addition of CH(4)
      (0.6-1.4 ml min(-1)), a sensitivity enhancement of more than one order of
      magnitude for selected analytes (e.g. (75)As(+)) was observed. In addition to the
      sensitivity enhancement for As, Te, I and Se, also all other measured elements
      showed a significantly enhanced sensitivity (minimum by a factor of 2). Potential
      mechanisms for the observed intensity enhancement include charge transfer
      reactions, a change in the ICP shape and a temperature increase in the plasma.
      Furthermore, the aspiration of a methanol-water mixture into a cooled spray
      chamber and the simultaneous addition to the laser ablated aerosol was
      investigated. This type of mixing leads to a sensitivity enhancement up to a
      factor of 20. To prevent clogging of the sampler cone and skimmer cone by carbon
      deposition, a fast cleaning procedure for the interface is tested during running
      ICP, which allows the application of such a set-up for specific applications.

PMID- 21881666
TI  - Aptameric system for the highly selective and ultrasensitive detection of protein
      in human serum based on non-stripping gold nanoparticles.
AB  - A novel approach is proposed in this study for the development of an aptameric
      assay system for protein based on non-stripping gold nanoparticles (NPs)
      triggered chemiluminescence (CL) upon target binding. The strategy chiefly
      depends on the formation of a sandwich-type immunocomplex among the capture
      antibody immobilized on the polystyrene microwells, target protein and aptamer
      functionalized gold NPs. Introduction of target protein into the assay system
      leads to the attachment of gold NPs onto the surface of the microwells and thus
      the assembled gold NPs could trigger the reaction between luminol and AgNO(3)
      with a CL emission. Further signal amplification was achieved by a simple gold
      metal catalytic deposition onto the gold NPs. Such an amplified CL transduction
      allowed for the detection of model target IgE down to the 50 fM, which is better
      than most existing aptameric methods for IgE detection. This new protocol also
      provided a good capability in discriminating IgE from nontarget proteins such as
      IgG, IgA, IgM and interferon. The practical application of the proposed gold NPs
      based immunoassay was successfully carried out for the determination of IgE in 35
      human serum samples. Overall, the proposed assay system exhibits excellent
      analytical characteristics (e.g., a detection limit on the attomolar scale and a
      linear dynamic range of 4 orders of magnitude), and it is also straightforward to
      adapt this strategy to detect a spectrum of other proteins by using different
      aptamers. This new CL strategy might create a novel technology for developing
      simple biosensors in the sensitive and selective detection of target protein in a
      variety of clinical, environmental and biodefense applications.

PMID- 21881667
TI  - Fullerenol entrapment in calcite microspheres.
AB  - Hybrid microspheres of calcium carbonate/fullerenol were synthesized and
      characterized. Their morphology depends on the concentration of the fullerenol
      solutions. XRD and FT-IR measurements proved that the mineral phase is
      consistently calcite, while fluorescence confocal microscopy indicated that
      fullerenol is homogenously included in the crystalline matrix.

PMID- 21881668
TI  - Yeast cell wall particles: a promising class of nature-inspired microcarriers for
      multimodal imaging.
AB  - This communication demonstrates that yeast cell wall particles (YCWPs) are a
      promising class of nature-inspired biocompatible microcarriers for the delivery
      of amphipathic/lipophilic imaging reporters. When a paramagnetic MRI agent is
      loaded, the longitudinal relaxivity per particle at 0.5 T is the highest ever
      reported for Gd-based systems.

PMID- 21881669
TI  - Local structural distortion of BaZr(x)Ti(1-x)O3 nanocrystals synthesized at room
      temperature.
AB  - Single crystalline, sub-15 nm BaZr(x)Ti(1-x)O(3) (0 <=x<= 1) nanocrystals were
      synthesized at room temperature via the vapor diffusion sol-gel method. As
      prepared nanocrystals exhibit noncentrosymmetric regions whose volume fraction
      increases significantly upon substitution of small amounts of Zr(4+) for Ti(4+)
      and reaches a maximum for substitution levels ranging from 10 to 20 mol%.

PMID- 21881670
TI  - Cold heteromolecular dipolar collisions.
AB  - Cold molecules promise to reveal a rich set of novel collision dynamics in the
      low-energy regime. By combining for the first time the techniques of Stark
      deceleration, magnetic trapping, and cryogenic buffer gas cooling, we present the
      first experimental observation of cold collisions between two different species
      of state-selected neutral polar molecules. This has enabled an absolute
      measurement of the total trap loss cross sections between OH and ND(3) at a mean
      collision energy of 3.6 cm(-1) (5 K). Due to the dipolar interaction, the total
      cross section increases upon application of an external polarizing electric
      field. Cross sections computed from ab initio potential energy surfaces are in
      agreement with the measured value at zero external electric field. The theory
      presented here represents the first such analysis of collisions between a (2)Pi
      radical and a closed-shell polyatomic molecule.

PMID- 21881671
TI  - Thiourea dioxide promoted efficient organocatalytic one-pot synthesis of a
      library of novel heterocyclic compounds.
AB  - The utility of thiourea dioxide as an efficient organocatalyst for the library
      synthesis of novel heterocyclic compounds via one-pot multicomponent coupling
      reactions is disclosed. Thiourea dioxide is an inexpensive and readily accessible
      catalyst, resulting in better product yields as compared to the corresponding
      thiourea as catalyst. Thiourea dioxide is found to be insoluble in various
      organic solvents and therefore at the end of the reaction products can be
      separated by extraction with diethyl ether and the recovered catalyst can be used
      several times with consistent catalytic activity.

PMID- 21881672
TI  - Highly sensitive rapid chemiluminescent immunoassay using the DNAzyme label for
      signal amplification.
AB  - A novel trace tag for chemiluminescent (CL) immunoassay was designed by using
      DNAzyme to functionalize antibody-labeled Au nanoparticles (AuNPs). The trace tag
      showed an excellent ability to catalyze the oxidation of luminol by hydrogen
      peroxide, leading to strong CL emission. By coupling the trace tag with a passive
      mixing accelerated immunoreaction system, a highly sensitive rapid flow-through
      CL immunoassay method was proposed. Using carcinoembryonic antigen (CEA) as a
      model analyte, the capture antibody for CEA was immobilized on paramagnetic
      microspheres, and DNAzyme-anti-CEA antibody functionalized AuNPs were prepared as
      trace tag. A three-dimensional helical glass tube kept at 37  degrees C in a
      water bath was used for passively mixing immunoreagents in a two-step sandwich
      immunoassay, with which each immunoreaction step could be finished within 150 s.
      With the help of a magnet, the immunocomplex could conveniently be separated from
      reactants. Compared with the horseradish peroxidase-based tag, the newly designed
      trace tag showed obvious signal amplification due to its strong catalytic ability
      and high loading ratio of DNAzyme on each AuNP. The proposed method showed a
      linear calibration range from 0.005 to 0.5 ng mL(-1) for CEA detection with a
      detection limit of 4.1 pg mL(-1) at a signal-to-noise ratio of 3 and acceptable
      detection reproducibility. The assay results of clinical serum samples were in
      acceptable agreement with the reference values. The designed immunoassay system
      with ultrahigh sensitivity provided a programmable and low-cost approach for high
      throughput clinical application.

PMID- 21881673
TI  - The role of the atomic charges on the ligands and platinum(II) in affecting the
      cis and trans influences in [PtXL(PPh3)2]+ complexes (X = NO3, Cl, Br, I; L = 4
      substituted pyridines, amines, PPh3). A 31P NMR and DFT investigation.
AB  - One bond Pt-P coupling constants (1)J(PtP) of a series of cationic complexes
      [PtXL(PPh(3))(2)](+) (X = NO(3), Cl, Br, I; L = 4-Z-pyridines, Z = electron
      withdrawing or releasing groups, 4a-k; or X = Cl, L = NH(3), PhCH(2)NH(2) and
      (i)PrNH(2), 5a-c) have been used to establish the trans and cis influence
      sequences of X and pyridines. The crystal structure of compound 4f(BF(4)) with Z
      = (t)Bu has been resolved. In the pyridine complexes 4a-d (Z = H, variable X),
      both the trans and cis influence series of the anionic ligands X decrease along
      the same sequence I > Br > Cl > NO(3), as previously found for
      [PtX(PPh(3))(3)](+) (X = NO(3), Cl, Br, I, 3a-d), however in 4a-d the cis
      influence turns out to be more important than the trans. On the contrary, in
      [PtCl(4-Z-py)(PPh(3))(2)](+) (4b,e-k) the sequence of the trans influence of the
      4-Z-pyridines is opposite to that of the cis, the latter being Z = CN > CHO > Br
      > PhCO > H > Me > (t)Bu > NH(2), i.e. the most basic pyridine gives rise to the
      lowest cis influence. This correlation was found to hold also for complexes 5a-c
      (L = amines). All the observed trends have been fully reproduced by B3LYP/def2
      SVP DFT calculations, by looking at the relevant optimized bond lengths of
      selected complexes of type 3, 4 and 5. Subsequent evaluation of the atomic
      charges, by resorting to two independent methods, i.e., the Natural Bond Order
      analysis of the wavefunction and the Bader's Quantum Theory of Atoms in
      Molecules, allowed for rationalization of the origin of the cis and trans
      influences. The negative charge on the nitrogen atoms of free pyridines becomes
      more negative upon protonation and even more so when coordinated to the
      [PtCl(PPh(3))(2)](+) moiety. The least negatively charged nitrogen atom of
      coordinated pyridines is that of 4-CN-py (the highest cis influencing pyridine
      derivative), which gives rise to the lowest positive charge on Pt, confirming the
      relationship between the lowering of the charge on the metal ion and a high cis
      influence. The trans influence can be described in terms of competition between
      the charges on the two trans donor atoms. In contrast with the behaviour of
      pyridines, the positive charge on the phosphorous atom of free PPh(3) increases
      upon coordination to Pt(II), moreover the PPh(3) ligands acquire a substantial
      positive charge, thus efficiently delocalising the charge of the cationic
      complex.

PMID- 21881674
TI  - Simultaneously targeting mitochondria and endoplasmic reticulum by photodynamic
      therapy induces apoptosis in human lymphoma cells.
AB  - Photodynamic therapy (PDT) and photodetection with protoporphyrin IX (PpIX)
      precursors have widely been used in the diseases with abnormally proliferative
      cells, but the mechanism of the modality is not fully understood yet. In this
      study 70-95% of apoptotic cells after PDT with PpIX precursor, hexaminolevulinate
      (HAL) in two human lymphoma cell lines, Namalwa and Bjab, were confirmed by
      fluorescence microscopy, electron microscopy and flow cytometry. HAL-derived PpIX
      was mainly distributed in the mitochondria and endoplasmic reticulum (ER), both
      of which were initial targets after light exposure causing two major pathways
      simultaneously involved in the apoptotic induction. One was the mitochondrial
      pathway including the release of cytochrome c, cleavage of caspases-9/-3,
      poly(ADP-ribose) polymerase and DNA fragmentation factor. The other was the ER
      stress-mediated pathway triggering a transient increase in the cytosolic Ca(2+)
      level after photodamage to the ER calcium pump protein SERCA2. The released
      Ca(2+) further initiated the caspase-8 cleavage. The use of both extracellular
      Ca(2+) chelator EGTA and intracellular Ca(2+) chelator BAPTA-AM confirmed that
      such cytosolic Ca(2+) originated from the ER rather than extracellular Ca(2+)
      containing medium. About 30% of the apoptosis was blocked with BAPTA-AM alone;
      while a complete inhibition of such apoptosis was achieved with a combination of
      the caspase-9 inhibitor Z-LEHD-FMK and caspase-8 inhibitor Z-IETD-FMK, thus
      quantifying each role of the mitochondrial and ER pathways.

PMID- 21881675
TI  - Hydrogen bonded supramolecular polymers in moderately polar solvents.
AB  - Hydrogen bonded assemblies are usually decomposed by polar organic solvents.
      However, we have succeeded in preparing a strongly associated supramolecular
      polymer which forms viscous solutions in competitive solvents such as
      tetrahydrofuran.

PMID- 21881676
TI  - 17 e- rhenium dicarbonyl CO-releasing molecules on a cobalamin scaffold for
      biological application.
AB  - Cyanocobalamin (B(12)) offers a biocompatible scaffold for CO-releasing 17
      electron dicarbonyl complexes based on the cis-trans-[Re(II)(CO)(2)Br(2)](0)
      core. A Co-C=N-Re conjugate is produced in a short time and high yield from the
      reaction of [Et(4)N](2)[Re(II)Br(4)(CO)(2)] (ReCORM-1) with B(12). The B(12)
      Re(II)(CO)(2) derivatives show a number of features which make them
      pharmaceutically acceptable CO-releasing molecules (CORMs). These cobalamin
      conjugates are characterized by an improved stability in aqueous aerobic media
      over the metal complex alone, and afford effective therapeutic protection against
      ischemia-reperfusion injury in cultured cardiomyocytes. The non-toxicity (at MUM
      concentrations) of the resulting metal fragment after CO release is attributed to
      the oxidation of the metal and formation in solution of the ReO(4)(-) anion,
      which is among the least toxic of all of the rare inorganic compounds.
      Theoretical and experimental studies aimed at elucidating the aqueous chemistry
      of ReCORM-1 are also described.

PMID- 21881677
TI  - Integration of cell phone imaging with microchip ELISA to detect ovarian cancer
      HE4 biomarker in urine at the point-of-care.
AB  - Ovarian cancer is asymptomatic in the early stages and most patients present with
      advanced levels of disease. The lack of cost-effective methods that can achieve
      frequent, simple and non-invasive testing hinders early detection and causes high
      mortality in ovarian cancer patients. Here, we report a simple and inexpensive
      microchip ELISA-based detection module that employs a portable detection system,
      i.e., a cell phone/charge-coupled device (CCD) to quantify an ovarian cancer
      biomarker, HE4, in urine. Integration of a mobile application with a cell phone
      enabled immediate processing of microchip ELISA results, which eliminated the
      need for a bulky, expensive spectrophotometer. The HE4 level detected by a cell
      phone or a lensless CCD system was significantly elevated in urine samples from
      cancer patients (n = 19) than healthy controls (n = 20) (p < 0.001). Receiver
      operating characteristic (ROC) analyses showed that the microchip ELISA coupled
      with a cell phone running an automated analysis mobile application had a
      sensitivity of 89.5% at a specificity of 90%. Under the same specificity, the
      microchip ELISA coupled with a CCD had a sensitivity of 84.2%. In conclusion,
      integration of microchip ELISA with cell phone/CCD-based colorimetric measurement
      technology can be used to detect HE4 biomarker at the point-of-care (POC), paving
      the way to create bedside technologies for diagnostics and treatment monitoring.

PMID- 21881678
TI  - Modulating substrate specificity of histone acetyltransferase with unnatural
      amino acids.
AB  - Controlling the substrate specificity of enzymes is a major challenge for protein
      engineers. Here we explore the effects of residue-specific incorporation of ortho
      , meta- and para-fluorophenylalanine (oFF, mFF, pFF) on the selectivity of human
      histone acetyltransferase (HAT) protein, p300/CBP associated factor (PCAF).
      Varying the position of the fluorine group in the phenylalanine ring confers
      different effects on the ability of PCAF to acetylate target histone H3 as well
      as non-histone p53. Surprisingly, pFF-PCAF exhibits an increase in activity for
      non-histone p53, while mFF-PCAF is selective for histone H3. These results
      suggest that global incorporation of unnatural amino acids may be used to re
      engineer protein specificity.

PMID- 21881679
TI  - Patterns of indirect protein interactions suggest a spatial organization to
      metabolism.
AB  - It has long been believed that cells organize their cytoplasm so as to
      efficiently channel metabolites between sequential enzymes. This metabolic
      channeling has the potential to yield higher metabolic fluxes as well as better
      regulatory control over metabolism. One mechanism for achieving such channeling
      is to ensure that sequential enzymes in a pathway are physically close to each
      other in the cell. We present evidence that indirect protein interactions between
      related enzymes represent a global mechanism for achieving metabolic channeling;
      the intuition being that protein interactions between enzymes and non-enzymatic
      mediator proteins are a powerful means of physically associating enzymes in a
      modular fashion. By analyzing the metabolic and protein-protein interactions
      networks of Escherichia coli, yeast and humans, we are able to show that all
      three species have many more indirect protein interactions linking enzymes that
      share metabolites than would be expected by chance. Moreover, these interactions
      are distributed non-randomly in the metabolic network. Our analyses in yeast and
      E. coli show that reactions possessing such interactions also show higher flux
      than do those lacking them. On the basis of these observations, we suggest that
      an important role of protein interactions with mediator proteins is to contribute
      to the spatial organization of the cell. This hypothesis is supported by the fact
      that these mediator proteins are also enriched with annotations related to signal
      transduction, a system where scaffolding proteins are known to limit cross-talk
      by controlling spatial localization.

PMID- 21881680
TI  - Dismal management of hypertension at primary level: does it reflect a failure of
      patients, a failure of the system or a failure of doctors?

PMID- 21881681
TI  - Late surgical treatment of tetralogy of Fallot.
AB  - AIM: To study early post-operative results and follow up of patients over a year
      old, operated on for tetralogy of Fallot (ToF). METHODS: This retrospective
      analysis included 22 patients (14 male and eight female) with a mean age of 9.18
      +/- 6.5 years (range 13.5 months to 26 years), who underwent complete repair of
      ToF between April 2003 and June 2009. Data from patients' records, pre-operative
      cardiac catheterisation studies, operative intervention, and pre-operative and
      postoperative two-dimensional echocardiographic studies were reviewed. All
      patients underwent complete repair including closure of ventricular septal defect
      (VSD). A trans-annular patch was used in 12 patients while an infundibular patch
      was used in 10 others. Patients were evaluated one, three, six and 12 months
      after surgery, and annually thereafter. The duration of follow up was from eight
      months to six years post surgery. RESULTS: Classical ToF was found in 10
      patients. Twelve cases had associated anomalies: two patients with hypoplastic
      pulmonary artery branches, two with arterial duct malformations, and eight had
      proximal stenosis of the left branch of the pulmonary artery. NHYA class
      distribution was as follows: class I: two patients; class II: five subjects;
      class III: 10 patients; class IV: five subjects. The mean stay in hospital was 15
      +/- 7 days. Two patients (9%) died during the early post-surgical period. At a
      mean follow-up interval of 32 +/- 9 months, all patients were asymptomatic and in
      NYHA class I. No late deaths occurred. In three patients, we registered isolated
      monomorphic ventricular extrasystoles. The right ventricle outflow tract (RVOT)
      pressure gradient was 29 +/- 1.5 mmHg in the acute post-surgical period and it
      did not change significantly during follow up. The right ventricular function was
      defined as normal in 95% of the patients in the study and was mildly depressed in
      5%. CONCLUSION: Even if treated later in life, our study showed very good
      surgical results of patients with ToF.

PMID- 21881682
TI  - Colour M-mode superiority in evaluation of improvement in myocardial performance
      indices following successful percutaneous coronary intervention (PCI).
AB  - AIM: This study aimed at evaluating the early effects of successful elective
      percutaneous coronary intervention (PCI) on systolic and diastolic function.
      METHODS: We consecutively studied the systolic and diastolic function in 21
      patients with stable coronary artery disease (CAD) and left ventricular ejection
      fraction (LVEF) > 40% before and 48 hours after successful elective PCI. RESULTS:
      Tei index and systolic indices (LVEF, regional wall motion abnormality score,
      tricuspid annular plane systolic excursion and peak systolic velocity of mitral
      and tricuspid annulus) did not change significantly. Among the diastolic indices,
      only velocity propagation (Vp) improved significantly (from 42.9 +/- 10.8 to 51.8
      +/- 10.7, p-value = 0.008) following PCI. Diastolic velocities, E/A ratio,
      deceleration time (DT), early and late diastolic velocities of mitral annulus in
      TDI, pulmonary vein systolic (PVs) and diastolic flow velocity (PVd) did not show
      significant improvement. CONCLUSION: Propagation velocity of mitral inflow was
      the earliest index to recover following successful PCI in patients with stable
      CAD.

PMID- 21881683
TI  - Health practitioners' state of knowledge and challenges to effective management
      of hypertension at primary level.
AB  - BACKGROUND: Patient- and physician-related factors impact on the management and
      control of hypertension. OBJECTIVES: To systematically examine: (1) South African
      primary care doctors' state of knowledge on the management of hypertension; (2)
      primary health practitioners' knowledge on the South African hypertension
      guidelines; (3) current approaches to management of hypertensive patients; and
      (4) challenges to effective management of hypertension at primary level. METHODS:
      A cross-sectional, observational study using a semi-structured questionnaire was
      carried out in two large community health centres (CHCs) in the Cape Town
      metropole. All 16 doctors employed at both CHCs were voluntarily enrolled, seven
      (43.7%) of whom were female, with 14 (87.5%) younger than 40 years of age. The
      majority (81.2%) of the doctors surveyed had been practicing for less than 10
      years. RESULTS: Ten (62.5%) of the doctors surveyed aimed to treat hypertension
      to target, and recommendations on lifestyle modifications were reportedly poorly
      done. While 11 (68.8%) of the doctors were aware of the South African
      hypertension guidelines, were (81.8%) of them were not conversant with the
      contents thereof. Doctors estimated that only 35% of their patients are treated
      to target. Poor patient adherence to prescribed treatment, language difficulty,
      heavy patient load, medical staff shortages, and patient loss to follow up were
      identified by the doctors as significant impediments to the effective management
      of hypertension at the primary level of care. CONCLUSION: Primary healthcare
      practitioners' knowledge regarding hypertension and the South African
      hypertension guidelines is poor. Management of hypertension by these doctors is
      sub-optimal. There are significant challenges to effective management of
      hypertension at this level of care.

PMID- 21881684
TI  - The state of heart disease in Sudan.
AB  - Cardiovascular disease (CVD) is the leading cause of mortality worldwide and an
      important cause of disability. In Africa, the burden of CVD is increasing rapidly
      and it is now a public health concern. Epidemiological data on diseases is scarce
      and fragmented on the continent. AIM: To review available data on the
      epidemiology and pattern of heart disease in Sudan. METHODS: Data were obtained
      from the Sudan Household Survey (SHHS) 2006, annual health statistical reports of
      the Sudan Federal Ministry of Health, the STEPS survey of chronic disease risk
      factors in Sudan/Khartoum, and journal publications. RESULTS: The SHHS reported a
      prevalence of 2.5% for heart disease. Hypertensive heart disease (HHD), rheumatic
      heart disease (RHD), ischaemic heart disease (IHD) and cardiomyopathy constitute
      more than 80% of CVD in Sudan. Hypertension (HTN) had a prevalence of 20.1 and
      20.4% in the SHHS and STEPS survey, respectively. There were poor control rates
      and a high prevalence of target-organ damage in the local studies. RHD prevalence
      data were available only for Khartoum state and the incidence has dropped from
      3/1 000 people in the 1980s to 0.3% in 2003. There were no data on any other
      states. The coronary event rates in 1989 were 112/100 000 people, with a total
      mortality of 36/100 000. Prevalence rates of low physical activity, obesity, HTN,
      hypercholesterolaemia, diabetes and smoking were 86.8, 53.9, 23.6, 19.8, 19.2 and
      12%, respectively, in the STEPS survey. Peripartum cardiomyopathy occurs at a
      rate of 1.5% of all deliveries. Congenital heart disease is prevalent in 0.2% of
      children. CONCLUSION: Heart diseases are an important cause of morbidity and
      mortality in Sudan. The tetrad of hypertension, RHD, IHD and cardiomyopathy
      constitute the bulk of CVD. Hypertension is prevalent, with poor control rates. A
      decline in rheumatic heart disease was seen in the capital state and no data were
      available on other parts of the country. No recent data on IHD were available.
      Peripartum cardiomyopathy and congenital heart disease occur at similar rates to
      those in other African countries.

PMID- 21881685
TI  - Progressive human immunodeficiency virus-associated vasculopathy: time to revise
      antiretroviral therapy guidelines?
AB  - Cardiovascular abnormalities were appreciated early in the epidemic of the
      acquired immunodeficiency syndrome (AIDS), even before the aetiological agent,
      human immunodeficiency virus (HIV) was isolated and characterised. The aetiology
      and pathogenesis of cardiovascular disease in HIV infection is still the subject
      of intense speculation, and is likely multi-factorial. HIV affects every aspect
      of the cardiac axis, causing pericarditis, myocarditis, cardiomyopathy, coronary
      artery disease and microvascular dysfunction, valvular heart disease, pulmonary
      vascular disease and pulmonary hypertension, stroke and peripheral vascular
      disease. HIV-associated vasculopathy is an increasingly recognised clinical
      entity, causing high morbidity and increasing mortality in southern Africa,
      particularly from stroke and cardiovascular disease. HIV causes disease of the
      vascular tree, either by a direct effect on vascular or perivascular tissue, or
      indirectly via immune complex-mediated mechanisms, associated opportunistic
      infections and malignancies. As a result, highly active antiretroviral therapy
      (HAART) may have an important role in controlling disease progression. We report
      a case of histologically defined primary HIV vasculopathy in which the chance to
      start HAART was initially missed and in which the patient progressed to require
      bilateral amputations, but obtained disease quiescence upon commencement of
      HAART.

PMID- 21881686
TI  - Subclavian crush syndrome: a cause of pacemaker lead fracture.
AB  - A 48-year-old male with a symptomatic 2:1 atrio-ventricular block and a dual
      chamber pacemaker, implanted one year previously, was admitted due to a syncopal
      episode. Pacemaker malfunction was identified as the cause of syncope. Subclavian
      crush syndrome was the cause of the pacemaker malfunction. Its incidence,
      consequences and management are discussed in this report.

PMID- 21881687
TI  - Diagnosis of a congenitally corrected transposition of the great arteries in a 50
      year-old multiparous woman.
AB  - Congenitally corrected transposition of the great arteries (cc-TGA) is a rare
      congenital heart disease. In the literature, few patients with this anomaly have
      been reported to be asymptomatic until after the fifth decade. We describe a 50
      year-old female with five pregnancies and successful deliveries, who was
      unrecognised until late in her fifth decade.

PMID- 21881688
TI  - The sensitivity of waist-to-height ratio in identifying children with high blood
      pressure.
AB  - We determined the sensitivity of waist-to-height ratio (WHtR) as a marker for
      high blood pressure in children aged nine to 15 years (n = 1 131), from schools
      in the North West province, South Africa. Anthropometric and blood pressure
      measurements were taken. The sensitivity and specificity of the WHtR to identify
      children with high blood pressure were evaluated. At a cut-off value of 0.5, 7.9%
      of the girls and 3.4% of the boys had central adiposity. Thirteen per cent of the
      children were hypertensive. The optimal WHtR cut-off value to identify children
      with hypertension was 0.41 in both boys and girls. Positive correlations were
      observed between anthropometric indices. Using linear regression analyses, age
      and body mass index were significant predictors of high blood pressure in boys,
      while for girls it was height and weight. Results suggest that adopting a WHtR
      cut-off value < 0.5 could enhance the use of WHtR as a marker for high blood
      pressure in children.

PMID- 21881689
TI  - Malignant convulsive vasovagal syncope.
AB  - A patient was referred for evaluation of repeated episodes of syncope with loss
      of consciousness and convulsions. A dual-chamber pacemaker with rate-drop feature
      was implanted.

PMID- 21881692
TI  - New data support ivabradine use in chronic heart failure.

PMID- 21881693
TI  - Torsades de pointes.

PMID- 21881694
TI  - FDA approves rivaroxaban for prevention of deep-vein thrombosis in surgery.

PMID- 21881695
TI  - South Africa's poor warfarin control raises questions of benefit above other
      anticoagulant therapies in atrial fibrillation.

PMID- 21881696
TI  - Obesity and platelet reactivity: the relationship remains uncertain.

PMID- 21881697
TI  - ARBs for cardiovascular and renal protection in high-risk patients.

PMID- 21881698
TI  - Safe use of ezetimibe plus simvastatin in high-risk vascular patients (with
      chronic kidney disease and PAD).

PMID- 21881699
TI  - Torulopsis glabrata endocarditis in a retro-positive individual.

PMID- 21881700
TI  - Phospholipid inhibitors. State of the art.
AB  - The antiphospholipid syndrome (APS) is defined by the association of arterial
      and/or venous thrombosis and/or pregnancy complications with the presence of at
      least one among the main antiphospholipid antibodies (aPL) (i. e., Lupus
      anticoagulants, LA, IgG and/or IgM anticardiolipin antibodies, aCL, IgG and/or
      IgM antibeta2-glycoprotein I antibodies, abeta2-GPI). Several clinical studies
      have consistently reported that LA is a stronger risk factor for both arterial
      and venous thrombosis compared to aCL and abeta2-GPI. In particular, LA activity
      dependent on the first domain of beta2-GPI and triple aPL positivity are
      associated with the risk of thrombosis and obstetrical complications. 
      Asymptomatic aPL-positive subjects do not require primary thromboprophylaxis.
      Venous thromboembolism is the most common initial clinical manifestation of APS.
      To prevent its recurrence indefinite anticoagulation is recommended. Long
      duration treatment with warfarin or aspirin is used after a first cerebral
      arterial thrombosis. Low molecular weight heparin (LMWH) with or without aspirin
      is recommended to reduce the rate of obstetrical complications of APS pregnant
      women.

PMID- 21881701
TI  - BJCVS: 25 years of brilliant career.

PMID- 21881702
TI  - The aorta, the elastic tissue and cystic medial necrosis.

PMID- 21881703
TI  - The surgeon.

PMID- 21881704
TI  - The 2000 Bernstein-Parsonnet score and EuroSCORE are similar in predicting
      mortality at the Heart Institute, USP.
AB  - OBJECTIVE: To evaluate the performance of 2000 Bernstein-Parsonnet (2000BP) and
      additive EuroSCORE (ES) for predicting surgical mortality at the Heart Institute,
      University of Sao Paulo. METHODS: A prospective observational design. Seven
      hundred and seventy four patients were operated for coronary artery bypass graft,
      valve or combined procedure between May and October, 2007, were analyzed. The
      mortality was estimated with the 2000BP and ES. The correlation between expected
      mortality and observed mortality was validated through calibration and
      discrimination test. RESULTS: The patients were stratified into five groups for
      the 2000BP and three for the ES. The Hosmer-Lemeshow test for 2000BP (P = 0.70)
      and for ES (P = 0.39) indicate a good calibration. The ROC curve for the 2000BP =
      0.84 and for the ES = 0.81 confirms that the models are good predictors
      (P<0.001). CONCLUSION: Both models are similar and adequate in predicting
      surgical mortality at the InCor-USP.

PMID- 21881705
TI  - The implications of serum enzymes and coagulation activities in postinfarction
      myocardial rupture.
AB  - OBJECTIVE: Associations between cardiovascular diseases and serum enzymes or
      coagulation activities have been sufficiently documented in patients with
      myocardial infarction. However, the alterations of these biomarkers in patients
      with postinfarction myocardial rupture have rarely been reported. The aim of this
      study is to present the profiles of the markers in patients with postinfarction
      myocardial rupture. METHODS: From 2004 to 2008, 19 consecutive patients were
      referred to this hospital for surgical repair of postinfarction myocardial
      rupture. Eight (42.1%) patients had free wall rupture, 5 (26.3%) had papillary
      muscle rupture, 5 (26.3%) had ventricular septal rupture, and 1 (5.3%) had double
      structure (ventricular septum + free wall) rupture. Thirteen patients survived
      the operation, and 6 died. Laboratory findings including serum enzymes and
      coagulation activities were collected and analyzed. RESULTS: The coagulation
      markers and serum enzymes except for fibrinogen increased significantly after the
      development of myocardial rupture. Statistical differences in D-dimer, partial
      thromboplastin time, peak lactate dehydrogenase, peak creatine kinase and
      creatine kinase fraction MB were found between non-survivors and survivors.
      Troponin I values were elevated significantly during the early days after the
      onset or surgical repair of myocardial rupture. Multivariant regression analysis
      did not show any significant relationship between creatine phosphokinase fraction
      MB (Y) and D-dimer (X1) or fibrinogen (X2). CONCLUSION: Myocardial rupture leads
      to extremely high serum enzyme and coagulation activities except for fibrinogen
      after the onset. The evaluation of these biomarkers may help in making diagnostic
      and treatment decisions and in judging the clinical prognosis of such patients.

PMID- 21881707
TI  - Long-term survival of octogenarian patients submitted to isolated coronary artery
      bypass graft surgery.
AB  - INTRODUCTION: An increasing number of octogenarian patients is undergoing
      coronary artery bypass graft surgery (CABG). The short-term results of this
      procedure have been broadly studied, but there are few national reports on long
      term outcomes. OBJECTIVES: To describe hospital mortality and long-term survival
      of patients aged > 80 years undergoing isolated CABG. METHODS: Retrospective
      cohort study with 142 consecutive patients aged > 80 years undergoing isolated
      CABG in the period between January/1996 and December/2007 in a Brazilian
      reference center. Mean age (A+/- SD) was 82.3 A+/- 2.1 years, and 56.3% were
      male. The prevalence of hypertension was 73.2%, of previous myocardial infarction
      30.3%, of diabetes 26.8%, and of renal dysfunction (creatinine 3 2.0 mg/ml) was
      4.9%. The median follow-up was 4.0 years, with a loss of 11.6% of patients.
      Survival analysis was performed by the Kaplan-Meier method. RESULTS: Overall
      hospital mortality was 14.8% (95% CI: 8.8 to 20.8), with a reduction of this rate
      during the study period (1996-1999: 25.9%, 2000-2003: 15.8%, and 2004-2007:
      8.6%). Mean survival was 6.5 years (95% CI: 5.5 to 7.5), and the survival rate at
      1, 3 and 5 years was 79.4, 73.4 and 65.2%, respectively. CONCLUSION: Results are
      in agreement with international reports. Mean survival was 6.5 years and the
      survival rate at 5 years was 65.2%.

PMID- 21881706
TI  - Nitrite exhaled breath condensate study in patients undergoing cardiopulmonary
      bypass cardiac surgery.
AB  - BACKGROUND: There is a relative lack of studies on postoperative changes in
      nitrite (NO2 - ) concentrations, a marker of injury, following cardiac surgery.
      In this context, investigations on how exhaled NO concentrations vary in the
      postoperative period of cardiac surgery will certainly contribute to new clinical
      findings. OBJECTIVE: The objective of this study was to compare the EBC NO levels
      in both the pre and postoperative (24 hours) periods of cardiac surgery. METHODS:
      Twenty - eight individuals were divided into three groups: 1) control, 2)
      coronary artery bypass grafting, and 3) valve surgery. The nitrite (NO2 - )
      levels were measured by chemiluminescence in blood samples and exhaled breath
      condensate (EBC). Data were analyzed by the Mann - Whitney and Wilcoxon tests.
      RESULTS: 1) Preoperatively, the EBC NO2 - levels from groups 2 and 3 patients
      were higher than control individuals; 2) The postoperative (24 hours) NO2 -
      levels in the EBC from group 3 patients were lower compared with preoperative
      values; 3) The NO2 - levels in the plasma from group 2 patients were lower in the
      preoperative compared with the postoperative (24h) values and; 4) Preoperatively,
      there was no difference between groups 2 and 3 in terms of plasma NO2 -
      concentrations. CONCLUSION: These data suggest that NO measurement in EBC is
      feasible in cardiac surgery patients.

PMID- 21881708
TI  - Risk factors for mediastinitis after coronary artery bypass grafting surgery.
AB  - OBJECTIVE: Mediastinitis is a serious complication of median sternotomy and is
      associated to significant morbidity and mortality. The aim of this study is to
      identify risk factors for mediastinitis in patients undergoing coronary artery
      bypass grafting (CABG), without the use of bilateral internal thoracic artery
      (ITA), at the Division of Cardiovascular Surgery of Pronto Socorro Cardiologico
      de Pernambuco - PROCAPE. METHODS: A retrospective study of 500 consecutive
      patients operated on between May 2007 and April 2010. Ten preoperative variables,
      seven intraoperative variables and seven postoperative variables possibly
      involved in the development of postoperative mediastinitis were evaluated.
      Univariate and multivariate logistic regression analyses were performed. RESULTS:
      The incidence of mediastinitis was 5.6% (n=28), with a lethality rate of 32.1%
      (n=9). In multivariate analysis using logistic regression, five variables
      remained as independent risk factors: obesity (OR 2.60, 95% CI 1.11 to 6.68),
      diabetes (OR 2.71, 95% CI 1.18 to 6.65), smoking (OR 2.10, 95% CI 1.12 to 4.67),
      use of pedicled internal thoracic artery (OR 5.17, 95% CI 1.45 to 18.42) and on
      pump CABG (OR 2.26, 95% CI 1.14 to 5.85). CONCLUSION: This study identified the
      following independent risk factors for mediastinitis after CABG: obesity,
      diabetes, smoking, use of pedicled ITA and on-pump CABG.

PMID- 21881709
TI  - Pediatric cardiac surgery under the parents sight: a qualitative study.
AB  - INTRODUCTION: Congenital heart defects can often be corrected through surgery,
      providing for parents to expect a normal life, but the hospitalization experience
      often early, causes more pain, for which surgery is the worst moment. OBJECTIVE:
      The aim of this study was to analyze the experience of families of children
      undergoing cardiac surgery and to identify the coping resources used by the
      families. METHODS: A qualitative approach was the metodology of choice for this
      study, which took place with six semi-structured interviews and 100 hours of
      observation. Thematic analysis was used to understand the data. RESULTS: The
      results were categorized into four themes: feelings and emotions facing the
      illness of the child; heart disease under the watchful mother, mother and child
      on the ICU and coping resources. The speech of mothers demonstrated the
      importance of the heart due to its symbolism that enhances their emotional
      fragility in the face of illness. Religiosity and a solid social network of
      support were contributing factors for the maintenance of the adaptive behaviors.
      The presence of mothers in all stages of the child's treatment contributed to
      minimizing the suffering generated by hospitalization. CONCLUSION: The experience
      of families was characterized by ambivalent feelings such as fear of death, guilt
      and helplessness against the different stages of treatment. The anguish and
      anxiety prevailed in the face of unknown situations when information were
      required before therapeutic procedures, hospital routines and the actual life
      situation of the families.

PMID- 21881710
TI  - Prevalence of myocardium revascularization wound infections surgery.
AB  - OBJECTIVE: To study the prevalence of wound infection on myocardial
      revascularization surgery stitches as well as the microorganisms Causing,
      predominant fri, acts and try to correlate it with the APACHE risk. METHODS: A
      retrospective and transversal study, with analysis of the files of the 21
      Patients with infected wounds myocardial revascularization operated Among 357
      Patients Between the years of 2007 and 2009. Were the files checked on 2009.
      RESULTS: There was in statistics Analyzing the Significance of the fri Patients.
      The average of Patients Were old aged and the prevalence is similar to the index
      found in literature, But There Are Variations about the microorganisms found all
      over the years. CONCLUSION: Besides the raise of wound infections along the three
      years, the prevalence Kept stable, once the numbers of surgeries maid raised
      proportionately. Fri Significant is not a variable to the Occurrence of
      myocardium revascularizations wound infection. Old aged people are more
      predictable to this complication and the microorganism is Causing variable.

PMID- 21881711
TI  - Thrombocytopenia in cardiac surgery: diagnostic and prognostic importance.
AB  - OBJECTIVE: Patients undergo to cardiac surgery have more probability to develop
      thrombocytopenia. The heparin induced thrombocytopenia happens in 5% of the
      patients. The aim from this study was to evaluate the clinical importance from
      the severe thrombocytopenia in postoperative cardiac surgical patients. METHODS:
      It was included cardiac surgical patients with platelets < 150000 cel/mm3 during
      firsts 24 h from postoperative. All patients underwent evaluation for four Ts
      score (thrombocytopenia, use preview of heparin, thrombosis and platelets
      decreased not related to heparin). In order to a four Ts score e" 6 was
      considered as suggestive of heparin induced thrombocytopenia type II. The
      mortality rate in intensive care (ICU) and hospital, length of stay, healthy
      state and incidence from thrombosis were compared in patients with score > 6
      (group 1) and < 6 (group 2). RESULTS: It was include 120 patients who met the
      inclusions criterions. There was no difference between the groups in related to
      age, gender, time of cardiopulmonary bypass and surgery. However, the incidence
      of thrombosis was higher in group 1 (23% vs. 0%, P<0.0001), as well as the
      greater score is related to higher hospital mortality rate. CONCLUSION: The score
      > 6, in postoperative cardiac surgical patients, it is associated to higher
      incidence of thrombosis as well as the greater score is related to higher
      hospital mortality rate.

PMID- 21881712
TI  - Pulmonary pressure checked by echocardiography in chagasic patients on the heart
      transplant waiting list.
AB  - INTRODUCTION: The patients suffering heart failure develop an increase in
      pulmonary pressure because of a retrograde mechanism. The pulmonary hypertension
      is a prognostic marker. OBJECTIVE: The aim of this study is to correlate
      pulmonary hypertension measured by echocardiogram versus catheterization in pre
      heart transplant patients on waiting list. METHODS: Data from 90 patients of the
      Clinical Hospital UFMG were collected between 2004 and 2009. All the patients
      took an echo and catheterization as an integral part of pre-heart transplant.
      Mean age was 45.5 years old, 68 (75.6%) male. Fourty-two (46.7%) were Chagas'
      disease patients, 32 (35.6%) presented idiopathic dilated cardiomyopathy, 10
      (11.1%) had ischemic cardyomiopathy. RESULTS: The mean eco-PASP was 45 +/-
      12mmHg). The mean cat-PASP was 47 +/-14mmHg. The eco-PASP-Chagas was 41.7 +/-12,5
      mmHg and non-Chagas 47.6 +/-12.8 mmHg P=0.04. The cat-PASP-Chagas was 46 +/-12.1
      mmHg and non-Chagas 48.7 +/-12.8 mmHg P=0.43. Eight patients had cat-PASP>60. The
      correlation between eco-PASP and cat-PASP in Chagas' patients was r=0.45; P=0.008
      and in the non-Chagas was r=0.66; P<0.001. The eco-PASP-Chagas>32,5mmHg has a
      sensitivity of 79% and specificity of 75% to diagnose PH, with an area under the
      curve of 0.819. The eco-PASP-non-Chagas>35.5 mmHg has a sensitivity of 82% and a
      specificity of 70% to diagnose PH, with an area under the curve of 0.776.
      CONCLUSIONS: There is a good correlation between eco-PASP and cat-PASP (r=0.54)
      in pre-heart transplant patients. The eco-PASP was lower in the Chagas' group.
      The echocardiogram is an important method to diagnosis and control pulmonary
      pressure in pre-heart transplant, specifically in Chagas' patients. The
      catheterization is still important to evaluate pulmonary reactivity during
      vasodilation test.

PMID- 21881713
TI  - Weight and height recovery in children with Down syndrome and congenital heart
      disease.
AB  - OBJECTIVE: To evaluate the impact of congenital heart diseases in growth of
      children with Down syndrome (DS) and the weight-height recovery after surgical
      correction. METHODS: Retrospective study of the DS patients between 1984 and
      2007. Excluding the mosaics and/or patients with associated morbidities (n=165).
      Calculated Z scores for weight (Zwb) and length (Zlb) at birth. Those patients
      submitted to surgical correction (n= 60) these scores (Zw/Zh) were evaluated
      before surgery and in subsequent periods to five years. Malnutrition was defined
      as weight/height Z-score < 2.5. Used Chi-square test to verify the relation
      between weight/length and age at the time of surgery and Student T test to
      evaluate the postoperative (PO) time of recovery (P < 0.05). RESULTS: Means Zwb
      (n = 162) and Zlb (n = 156) were -0.95 +/- 1.27 and -1.348 +/- 1.02. From the
      total data (n = 165), 65.5% (n = 108) presented heart disease. Those submitted to
      cardiac surgery (n = 60), Zw was below -2.5 in 55% (n = 33) and Zh in 60% (n =
      36). After six months PO, 67.4% achieved Zw > 2.5. In one year, 85.7% achieved Zh
      > 2.5. Dividing this group by age in tertiles at time of surgery no difference
      was found. CONCLUSIONS: We concluded that malnutrition common in children with DS
      since birth. DS children with congenital heart and surgical indication were
      smaller and lighter than those without or with mild disease. PO recovery occurred
      in 6 months for weight and one year for height, with no difference in the age at
      the time of surgery.

PMID- 21881714
TI  - Predictors of mortality in patients over 70 years-old undergoing CABG or valve
      surgery with cardiopulmonary bypass.
AB  - OBJECTIVE: To identify risk factors in septuagenarians and octogenarians
      submitted to cardiovascular surgery with cardiopulmonary bypass (CPB). METHODS:
      Per-operative variables of 265 patients over 70 years of age were analyzed. 248
      (93.6%) were septuagenarians and 17 (6.4%) octogenarians. RESULTS: Overall
      mortality did not differ between the groups, nor did the type of procedure (CABG
      or valvular) (P=0.545). Pre-operative variables did not increase the death risk,
      nor did the use of arterial or venous grafts (P=0.261), or the number of grafts
      per patient (P=0.131). CPB and cross-clamp time are associated with higher
      mortality. The survivors' group had an average CPB time of 70 +/- 27 minutes
      while the non-survivors group 88.8 +/- 25.4 minutes (P<0.001). Cross-clamp time
      in the survivors was 55.5 +/- 20 minutes, while 64.9 +/- 16 minutes in the non
      survivors (P=0.014). Using multivariate logistic regression, CPB time is
      associated with death (Pearson's chi square= 0.0056). CPB time over 75 minutes
      presents an increased risk of death of 3.2 times (CI 95%: 1.3-7.9) over those
      with CPB time < 75 minutes. Post-operative variables associated with increased
      death rates: mechanical ventilation > 12 hours (P<0.001); ICU stay (P=0.033); re
      exploration (P=0.001); inotropic support > 48 hours (P<0.001); use of blood
      components (P<0.001). CONCLUSION: Overall mortality justifies the interventions.
      CPB time greater than 75 minutes, mechanical ventilation over 12 hours, length of
      ICU stay, need for reoperation, inotropic drug support over 48 hours, and use of
      blood components are associated with a higher mortality rate.

PMID- 21881715
TI  - Experimental study of pulsatile implantable electromechanical artificial
      ventricle.
AB  - OBJECTIVE: The objective is to present the results of the application this device
      in experimental animals unloading only the left ventricle. METHODS: Between June
      2002 and October 2009, were implanted in 27 calfs with age between 21/2 to 4
      months and 80 to 100 kg of weight, with general anaesthesia and controled
      ventilation, by mean of left thoracotomy a cannula in the apex of VE and a
      lateral anastomose of a GTFE vascular graft tube in the descending portion of the
      thoracic aorta, both connected to the device implanted below the diaphragm in the
      subcutaneous (24) and intrathoracic (three). The cardiopulmonary bypass (BP) was
      used in five calves, and directly introduce the outflow cannula in 22. RESULTS:
      During the implant two and in the first hours of the post operative period (PO)
      three deaths were observed, one related to the device. The survival between the
      first and the six PO day was found in 17 calves and between day 8 and day 31 (PO)
      in five all caused by clinical/surgical problems, and related to the device. The
      hemodynamic impact by the systemic pressure analysis showed 20 to 40 mmHg
      increase and the laboratory parameters showed lower levels of traumatic impact to
      the blood and a good biocompatibility. CONCLUSIONS: This kind of research is
      arduous and complex where at each experiment many problems are indentified in the
      implantability and in the device, which are sistematic correct, to became
      device/procedure safe and effective.

PMID- 21881716
TI  - Long term results of septal myectomy in the treatment of obstructive hypertrophic
      cardiomyopathy.
AB  - OBJECTIVE: This study analyzed the clinical and echocardiographic late outcomes
      of surgical septal myectomy in patients with obstructive hypertrophic
      cardiomyopathy (OHCM). METHODS: We examined, retrospectively, 34 consecutive
      adult patients (age 55.7+/-15.2 years) with OHCM operated on in our institution
      from 1988 to 2008. Only four (11.8%) patients had family history of OHCM. Nine
      (26.5%) patients were in New York Heart Association (NYHA) funcional class IV.
      Thirty (88.2%) patients had solely OHCM, and four (11.8%) had OHCM associated
      with coronary insufficiency. The surgical technique used in all patients was
      septal myectomy performed through an aortotomy. RESULTS: In 26 (76.5%) patients
      the mitral insufficiency due to systolic anterior motion, decreased after the
      myectomy. Eight (23.5%) patients had mitral valve procedures. There was one
      hospitalar death (2.9%). Two (5.9%) patients required permanent pacemaker for
      complete heart block after the myectomy. The mean peak preoperative left
      ventricular outflow tract (LVOT) obstruction gradient was 84.9+/-29.0 mmHg, and
      decreased to 27.8+/-12.9 mmHg in the early postoperative and it was 19.2+/-11.2
      mmHg in the late postoperative period (49.0+/-33.0 months). The NYHA functional
      class improved from 3.1+/-0.8 to 1.4+/-0.5 in the postoperative period. Survival
      free from death was 87.9% and survival free from cardiovascular events was 77.7%
      with mean follow-up 9.6+/-8.4 years. CONCLUSION: Surgical septal myectomy can be
      performed safely, with excellent survival, improvement from symptoms and relief
      for LVOT obstruction in patients with OHCM. The early benefits were remained at
      long term.

PMID- 21881717
TI  - Surgical treatment of patent ductus arteriosus in adults.
AB  - OBJECTIVE: To analyze 34 patients submitted to surgical treatment of patent
      arterial duct with age beyond 18 years old. METHODS: Retrospective data collected
      from patient's charts with more than eighteen years old, submitted to surgical
      correction of patent arterial duct between 1997 and 2008 at Instituto do Coracao
      da Faculdade de Medicina da Universidade de Sao Paulo. RESULTS: The mean age was
      28.7 (18 a 53) years and 22 (64.7%) were female. The more prevalent symptom was
      dyspnea (76.5%). Left lateral thoracotomy was used in 33 (97.1%); the DA was
      sectioned and sutured in 25 (73.5%) cases and one patient needed cardiopulmonary
      bypass support. There were eight (23.5%) calcified arterial duct and 12 (35.3%)
      previous treatment with transcatheter devices were performed. The complication
      rate was 32%, with one (2.9%) permanent vocal cord palsy. Two (5.8%) patients had
      residual shunt less than 2mm. Transient left cord voice palsy was observed in 3
      (8.8%) The procedure improves functional class (P< 0.0001) and no mortality was
      observed. CONCLUSION: In this series, the surgical treatment of patent arterial
      duct in adults could be done without mortality and low incidence of
      complications.

PMID- 21881718
TI  - Anatomical eponyms in Cardiology from to the 60s to the XXI century.
AB  - BACKGROUND: Eponym from the Greek [epi, "upon"] + [onuma, name], is a person,
      whether real or fictitious, after whom an item is named or thought to be named.
      Eponymous terms are used every day in Medicine, in our clinical years, and they
      have been part of the tradition of Medicine, culture, and history. Despite all
      the inconvenience, all those who are no against eponym has only one statement:
      "medical eponyms will continue to be used because there is a sense of history to
      their use. They are use in contemporary life, eponyms are here to stay". METHODS:
      The following study aims at to show the presence of current anatomical eponyms on
      the best well-known Textbooks and Atlas of Human Anatomy, ranging from the oldest
      to the newest one, comprising a period from 1960 until 2011, regarding the
      cardiovascular system, particularly the heart. The three International Anatomical
      Terminologies have been critical as the basis of our study. Exclusion criteria
      were syndromes, diseases, signs, anomalies, surgical procedures, indexes, tests,
      grading, and the methods, which are used as eponyms in Cardiology, once they are
      not considered Anatomical Terms. It has been our intent to show that different
      eponyms characterize the same anatomical structure. RESULTS: A list with the 25
      most common eponyms listed by the three International Anatomical Terminologies is
      listed in Table1. CONCLUSION: Should eponyms be abandoned? Of course not, once
      they remain a useful reflection of medical history. We could prove to our journey
      from 1960 to 2011, that the best well-known Atlas and Textbooks available do not
      use so many anatomical eponyms in Cardiology. They are only 25 (without including
      arteries, veins, and nerves of the cardiovascular system) and all the authors use
      no more than 9 or 12 of them. We just want to alert the Health and Allied Health
      Sciences Professional and students that we 'strongly recommend' not to use an
      eponym when it is made at the expense of an anatomical structure.

PMID- 21881719
TI  - Cystic medial necrosis: pathological findings and clinical implications.
AB  - Cystic medial necrosis (CMN) is a disorder of large arteries, in particular the
      aorta, characterized by an accumulation of basophilic ground substance in the
      media with cyst-like lesions. CMN is known to occur in certain connective tissue
      diseases such as Marfan syndrome, Ehlers-Danlos syndrome, and annuloaortic
      ectasia, which usually result from degenerative changes in the aortic wall. The
      relationships between CMN and congenital heart defects as well as other disorders
      have been evidenced. The mechanisms are still controversial, even though many
      molecular studies have been conducted. The aim of the present article is to
      provide a comprehensive overview of the CMN lesion in terms of pathologic
      features, clinical implications and etiologies based on molecular research
      results.

PMID- 21881720
TI  - Alveolar recruitment in patients in the immediate postoperative period of cardiac
      surgery.
AB  - Lung complications during postoperative period of cardiac surgery are frequently,
      highlighting atelectasis and hypoxemia. Alveolar recruitment maneuvers have an
      important role in the prevention and treatment of these complications. Thus, this
      study reviewed and updated the alveolar recruitment maneuvers performance in the
      immediate postoperative period of cardiac surgery. We noted the efficacy of
      alveolar recruitment through different specific techniques and the need for
      development of new studies.

PMID- 21881721
TI  - Vacuum-assisted venous drainage in cardiopulmonary bypass and need of blood
      transfusion: experience of service.
AB  - OBJECTIVE: To report the experience with the vacuum-assisted venous drainage
      (VAVD) technique in cardiopulmonary bypass (CPBP) and blood transfusion need.
      METHODS: A retrospective study was made about data from 111 patients who were
      operated, using VAVD between October 2006 and February 2008, at the Esperanca
      Hospital, Recife, Pernambuco. The necessity of blood transfusion was verified on
      the single group of patients who underwent VAVD, comparing with sex, age and
      weigh, before the beginning of the CPBP and during the surgery, using Chi-square
      test and t-student test. RESULTS: Before the beginning of the CPBP only 10% of
      patients had need for blood transfusion and 12% during the surgery. It was
      observed that 17% of women received blood transfusion versus 4.7% of men before
      the beginning of CPBP (P=0.51), and 38% of women versus 9% of men during the
      surgery (P<0.001). The weight of patients who received blood transfusion were
      lower both before the beginning of the CPBP as during the surgery (P=0.049 e
      P=0.001, respectively). CONCLUSION: The VAVD technique has been used safely and
      satisfactorily, optimizing venous drainage during CPBP, in the hospital that
      conducted the study. However, prospective and comparative investigations between
      conventional drainage and VAVD are needed to better clarify this relation with
      blood transfusion.

PMID- 21881722
TI  - Ruptured thoracic aortic aneurysm in patient with systemic lupus erythematosus.
AB  - It is reported a ruptured descending thoracic aortic aneurysm in a 25-year-old
      systemic lupus erythematosus woman who underwent 19 years steroid therapy. She
      was treated with 2 endovascular stent-grafts, discharged from hospital 13 days
      after the procedure in good health. Three months later she returned with
      hemorrhagic shock due to high digestive hemorrhage secondary to an aortic
      esophageal fistula. She underwent to an open emergency surgery, and died during
      the post-operative period.

PMID- 21881723
TI  - Infected aneurysm of brachial artery after mitral valve infective endocarditis.
AB  - We present a case of brachial artery infected aneurysm in a patient with
      infective endocarditis caused by Streptococcus bovis. A 49-year-old man presented
      with fever dyspnea and a pansystolic murmur with irradiation to axilla. The
      echocardiogram revealed vegetation in native mitral valve. After mitral valve
      replacement with bioprosthesis, it was observed pulsatile mass of five
      centimeters in diameter at antecubital fossa of right upper limb. It was made the
      diagnosis of infected aneurysm of the brachial artery, and the surgery was
      performed successfully. The aim of this case report is to show a rare
      complication after infective endocarditis.

PMID- 21881724
TI  - Subvalvular aortic membrane resection.

PMID- 21881725
TI  - Fontan postoperative complication: antegrade pulmonary flow.

PMID- 21881726
TI  - Iseu Affonso da Costa, pioneer of the Brazilian heart surgery: my father, our
      pride!

PMID- 21881727
TI  - Lactate.

PMID- 21881729
TI  - Pharmacological treatment of COPD.

PMID- 21881730
TI  - The way forward in lymphangioleiomyomatosis: a trial for every patient, every
      patient in a trial.

PMID- 21881731
TI  - Doxycycline use in patients with lymphangioleiomyomatosis: safety and efficacy in
      metalloproteinase blockade.
AB  - OBJECTIVE: Lymphangioleiomyomatosis (LAM) is characterized by lung cysts, whose
      development is associated with matrix metalloproteinase (MMP) hyperactivity,
      principally that of MMP-2 and MMP-9. Our objective was to compare LAM patients
      and controls in terms of the levels of these MMPs, as well as to determine the
      safety and efficacy of treatment with doxycycline, a potent MMP inhibitor.
      METHODS: Prospective clinical study involving female LAM patients who received
      doxycycline (100 mg/day) for six months. Urine and blood samples were collected
      for the quantification of MMP-2 and MMP-9 before and after the treatment period.
      Samples from 10 healthy women were also collected. RESULTS: Of the 41 LAM
      patients who started the treatment, 34 completed the protocol. Serum and urinary
      MMP-9 levels were significantly lower in the controls than in the LAM patients (p
      < 0.0001). Comparing pre- and post-treatment values, we found that the median
      level of MMP-9 in serum decreased from 919 ng/mL to 871 ng/mL (p = 0.05), whereas
      that of MMP-9 in urine decreased from 11,558 pg/mL to 7,315 pg/mL (p = 0.10).
      After treatment, the median level of MMP-2 in serum was significantly lower (p =
      0.04) and urinary MMP-2 levels were undetectable. Nausea, diarrhea, and
      epigastric pain were the most prevalent adverse affects and were often self
      limiting. There was only one case in which the patient discontinued the treatment
      because of side effects. CONCLUSIONS: We have demonstrated, for the first time, a
      decrease in serum and urine levels of MMPs in LAM patients treated with
      doxycycline, which proved to be a safe medication, with mild and well-tolerated
      side effects.

PMID- 21881732
TI  - Clinical characteristics and prognosis in near-fatal asthma patients in Salvador,
      Brazil.
AB  - OBJECTIVE: To determine the frequency of near-fatal asthma in a group of severe
      asthma patients, as well as the clinical characteristics and prognosis of these
      patients within a one-year follow-up period. METHODS: A prospective study
      involving 731 low-income patients with severe asthma treated at a referral
      outpatient clinic located in the city of Salvador, Brazil. The patients were
      submitted to spirometry at admission, received medications for asthma, and were
      monitored regarding the frequency of asthma exacerbations during the follow-up
      period. A subsample of 511 patients also completed questionnaires regarding
      asthma symptoms and asthma-related quality of life. RESULTS: Of the 731 patients
      studied, 563 (77%) were female. The median age was 47 years, and 12% were
      illiterate. Most of the patients had rhinitis, and 70 patients (10%) reported
      near-fatal asthma prior to admission. Of these 70 patients, 41 (59%) reported
      having been intubated previously. The patients reporting a history of near-fatal
      asthma at admission were more likely to have asthma exacerbations during the
      follow-up period and to respond poorly to therapy than were those not reporting
      such a history. At the end of the follow-up period, the scores on the two
      questionnaires were similar between the two groups of patients. CONCLUSIONS: The
      frequency of near-fatal asthma was high in this group of low-income patients with
      severe asthma. The patients with a history of near-fatal asthma had a worse
      prognosis than did those without such a history, although both groups had
      received the same kind of treatment. Curiously, the intensity of symptoms and the
      quality of life at the end of the study were similar between the two groups.

PMID- 21881733
TI  - Epidemiological characteristics of sarcoidosis patients in the city of Rio de
      Janeiro, Brazil.
AB  - OBJECTIVE: To analyze the epidemiological characteristics of sarcoidosis patients
      in the city of Rio de Janeiro, Brazil. METHODS: A descriptive, case-control study
      involving 100 sarcoidosis patients under outpatient treatment between 2008 and
      2010 at the Pedro Ernesto University Hospital, located in the city of Rio de
      Janeiro, Brazil. The diagnosis of sarcoidosis was based on clinical,
      radiological, biochemical, and histopathological criteria. RESULTS: There was a
      predominance of females in the 35-40 year age bracket (range, 7-69 years), who
      accounted for 65% of the sample, although there was a second peak at
      approximately 55 years of age. The most common symptom was dyspnea (in 47%), and
      the most common radiological findings were pulmonary and lymph node involvement
      (stage II; in 43%), followed by stage III (in 20%), stage I (in 19%), stage 0 (in
      15%), and stage IV (in 3%). No pleural effusion or digital clubbing was observed
      at diagnosis. The tuberculin skin test was negative in 94 patients. Spirometric
      findings at diagnosis were normal in 61 patients; indicative of obstructive lung
      disease in 21; and indicative of restrictive lung disease in 18. The most common
      biopsy sites were the lungs (principally by bronchoscopy) and the skin, the
      diagnosis being confirmed by biopsy in 56% and 29% of the cases, respectively.
      Treatment with prednisone was initiated in 75% of the patients and maintained for
      more than 2 years in 19.7%. CONCLUSIONS: This study corroborates the findings of
      previous studies regarding the epidemiological characteristics of sarcoidosis
      patients.

PMID- 21881734
TI  - Dyspnea descriptors developed in Brazil: application in obese patients and in
      patients with cardiorespiratory diseases.
AB  - OBJECTIVE: To develop a set of descriptive terms applied to the sensation of
      dyspnea (dyspnea descriptors) for use in Brazil and to investigate the usefulness
      of these descriptors in four distinct clinical conditions that can be accompanied
      by dyspnea. METHODS: We collected 111 dyspnea descriptors from 67 patients and 10
      health professionals. These descriptors were analyzed and reduced to 15 based on
      their frequency of use, similarity of meaning, and potential pathophysiological
      value. Those 15 descriptors were applied in 50 asthma patients, 50 COPD patients,
      30 patients with heart failure, and 50 patients with class II or III obesity. The
      three best descriptors, as selected by the patients, were studied by cluster
      analysis. Potential associations between the identified clusters and the four
      clinical conditions were also investigated. RESULTS: The use of this set of
      descriptors led to a solution with seven clusters, designated sufoco
      (suffocating), aperto (tight), rapido (rapid), fadiga (fatigue), abafado
      (stuffy), trabalho/inspiracao (work/inhalation), and falta de ar (shortness of
      breath). Overlapping of descriptors was quite common among the patients,
      regardless of their clinical condition. Asthma was significantly associated with
      the sufoco and trabalho/inspiracao clusters, whereas COPD and heart failure were
      associated with the sufoco, trabalho/inspiracao, and falta de ar clusters.
      Obesity was associated only with the falta de ar cluster. CONCLUSIONS: In Brazil,
      patients who are accustomed to perceiving dyspnea employ various descriptors in
      order to describe the symptom, and these descriptors can be grouped into similar
      clusters. In our study sample, such clusters showed no usefulness in
      differentiating among the four clinical conditions evaluated.

PMID- 21881735
TI  - Dyspnea descriptors translated from English to Portuguese: application in obese
      patients and in patients with cardiorespiratory diseases.
AB  - OBJECTIVE: To investigate the usefulness of descriptive terms applied to the
      sensation of dyspnea (dyspnea descriptors) that were developed in English and
      translated to Brazilian Portuguese in patients with four distinct clinical
      conditions that can be accompanied by dyspnea. METHODS: We translated, from
      English to Brazilian Portuguese, a list of 15 dyspnea descriptors reported in a
      study conducted in the USA. Those 15 descriptors were applied in 50 asthma
      patients, 50 COPD patients, 30 patients with heart failure, and 50 patients with
      class II or III obesity. The three best descriptors, as selected by the patients,
      were studied by cluster analysis. Potential associations between the identified
      clusters and the four clinical conditions were also investigated. RESULTS: The
      use of this set of descriptors led to a solution with nine clusters, designated
      expiracao (exhalation), fome de ar (air hunger), sufoco (suffocating),
      superficial (shallow), rapido (rapid), aperto (tight), falta de ar (shortness of
      breath), trabalho (work), and inspiracao (inhalation). Overlapping of the
      descriptors was quite common among the patients, regardless of their clinical
      condition. Asthma, COPD, and heart failure were significantly associated with the
      inspiracao cluster. Heart failure was also associated with the trabalho cluster,
      whereas obesity was not associated with any of the clusters. CONCLUSIONS: In our
      study sample, the application of dyspnea descriptors translated from English to
      Portuguese led to the identification of distinct clusters, some of which were
      similar to those identified in a study conducted in the USA. The translated
      descriptors were less useful than were those developed in Brazil regarding their
      ability to generate significant associations among the clinical conditions
      investigated here.

PMID- 21881736
TI  - Early termination of exhalation: effect on spirometric parameters in healthy
      preschool children.
AB  - OBJECTIVE: To evaluate the acceptability and reproducibility of spirometry in
      preschool children; to estimate the effect size of early termination of
      exhalation (ETE) on FVC, FEV(1) and FEV(0.5); and to evaluate the validity of
      FEV(0.5) in curves with ETE. METHODS: Spirometric data were obtained from 240
      healthy preschool children, who were selected by simple sampling. On the basis of
      the best curve from each child according to the end of exhalation, three groups
      were formed: no ETE (nETE); ETE and flow <= 10% of the highest PEF (ETE<=10); and
      ETE and flow > 10% of the highest PEF value (ETE>10). The reproducibility of FVC,
      FEV(1) and FEV(0.5) was compared among the three groups. The effect of ETE on
      FVC, FEV(1), and FEV(0.5) was assessed. RESULTS: Of the 240 children tested, 112
      (46.5%)-82 (34.0%) of those in the nETE group and 30 (12.5%) of those in the
      ETE<=10 group--had acceptable curves for all the parameters. In 64 (27.0%) of
      those in the ETE>10 group, the curves were acceptable only for FEV(0.5),
      increasing the proportion of children with valid FEV(0.5) to 73.0%. There were no
      significant differences between the nETE and ETE<=10 groups in terms of the mean
      values of the parameters assessed. CONCLUSIONS: Maneuvers with ETE and flow <=
      10% of the highest PEF are valid. In individuals with a flow > 10% of the highest
      PEF value, these maneuvers are only valid for FEV(0.5).

PMID- 21881737
TI  - Mouth breathing and forward head posture: effects on respiratory biomechanics and
      exercise capacity in children.
AB  - OBJECTIVE: To evaluate submaximal exercise tolerance and respiratory muscle
      strength in relation to forward head posture (FHP) and respiratory mode in
      children, comparing mouth-breathing (MB) children with nasal-breathing (NB)
      children. METHODS: This was a controlled, analytical cross-sectional study
      involving children in the 8-12 year age bracket with a clinical
      otorhinolaryngology diagnosis of MB, recruited between October of 2010 and
      January of 2011 from the Mouth Breather Clinic at the State University of
      Campinas Hospital de Clinicas, located in the city of Campinas, Brazil. The
      exclusion criteria were obesity, asthma, chronic respiratory diseases, heart
      disease, and neurological or orthopedic disorders. All of the participants
      underwent postural assessment and the six-minute walk test (6MWT), together with
      determination of MIP and MEP. RESULTS: Of the 92 children in the study, 30
      presented with MB and 62 presented with NB. In the MB group, the differences
      between those with moderate or severe FHP and those with normal head posture, in
      terms of the mean MIP, MEP and six-minute walk distance (6MWD), were not
      significant (p = 0.079, p = 0.622, and p = 0.957, respectively). In the NB group,
      the mean values of MIP and MEP were higher in the children with moderate FHP than
      in those with normal head posture (p = 0.003 and p = 0.004, respectively). The
      mean MIP, MEP, and 6MWD were lower in the MB group than in the NB group. Values
      of MIP and MEP were highest in the children with moderate FHP. CONCLUSIONS:
      Respiratory biomechanics and exercise capacity were negatively affected by MB.
      The presence of moderate FHP acted as a compensatory mechanism in order to
      improve respiratory muscle function.

PMID- 21881738
TI  - Smoking cessation among patients at a university hospital in Curitiba, Brazil.
AB  - OBJECTIVE: To determine the prevalence of smoking and the frequency of smoking
      cessation counseling among patients at a university hospital, as well as to
      compare smokers and former smokers in terms of smoking history. METHODS: A cross
      sectional study involving 629 patients at the Federal University of Parana
      Hospital de Clinicas, located in the city of Curitiba, Brazil. RESULTS: Of the
      629 patients, 206 (32.7%) were male, 76 (12.1%) were smokers, 179 (28.5%) were
      former smokers, and 374 (59.5%) were nonsmokers. The mean age of the patients was
      49.9 +/- 15.0 years (range, 18-84 years). Of the 76 smokers and 179 former
      smokers, 72 (94.7%) and 166 (92.7%), respectively, were questioned about tobacco
      use. Smoking history and degree of nicotine dependence were higher among the
      former smokers (p = 0.0292 and p = 0.0125, respectively). Gender, age at smoking
      initiation, physician inquiry about tobacco use, and smoking cessation counseling
      were comparable between the two groups. The smoking cessation rate was 0.70. The
      prevalence of heavy smoking varied by gender and by age bracket, being higher in
      males and in the 41-70 year age bracket. CONCLUSIONS: The smoking prevalence in
      this group of patients was lower than that reported for patients at another
      university hospital, for adults in Curitiba, and for adults in Brazil. The
      smoking cessation rate was higher in these patients than in the general
      population of Curitiba. Smokers and former smokers differed regarding age,
      smoking history, and degree of nicotine dependence. Heavy smoking and a moderate
      or high degree of nicotine dependence were not obstacles to smoking cessation.

PMID- 21881739
TI  - Smoking among inpatients at a university hospital.
AB  - OBJECTIVE: To determine the prevalence and characteristics of smoking among
      inpatients at a university hospital, as well as to evaluate their motivation,
      interest, and need for help in quitting smoking. METHODS: A prospective study
      involving inpatients treated between May of 2008 and April of 2009 on the
      cardiovascular disease wards at the Antonio Pedro University Hospital, located in
      the city of Niteroi, Brazil. All inpatients were asked to complete a
      questionnaire designed to collect data regarding demographics, reasons for
      admission, and smoking status. The smokers also responded to additional questions
      regarding their smoking habits. The level of nicotine dependence was determined
      with the Fagerstrom Test for Nicotine Dependence. RESULTS: Of the 136 inpatients
      who participated in the study, 68 (50.0%) were male. The mean age was 60.7 years.
      The prevalence of smoking was 13.2%. Among the 49 patients with coronary disease,
      36 (73.5%) were smokers or former smokers. The majority of the patients presented
      with a high level of nicotine dependence and reported withdrawal symptoms during
      hospitalization. Although most smokers were motivated to quit smoking, they
      admitted that they needed help to do so. CONCLUSIONS: Because smoking is
      forbidden in the hospital environment and most inpatients who smoke are highly
      motivated to quit, health professionals should view the hospitalization period as
      an opportunity to promote smoking cessation.

PMID- 21881740
TI  - Comparing the accuracy of predictors of mortality in ventilator-associated
      pneumonia.
AB  - OBJECTIVE: Levels of procalcitonin, midregional pro-atrial natriuretic peptide
      (MR-proANP), C-terminal provasopressin (copeptin), and C-reactive protein (CRP),
      as well as Sequential Organ Failure Assessment (SOFA) scores, are associated with
      severity and described as predictors of outcome in ventilator-associated
      pneumonia (VAP). This study sought to compare the predictive value of these
      biomarkers for mortality in VAP. METHODS: An observational study of 71 patients
      with VAP. Levels of procalcitonin, MR-proANP, copeptin, and CRP, together with
      SOFA scores, were determined at VAP onset, designated day 0 (D0), and on day 4 of
      treatment (D4). Patients received empirical antimicrobial therapy, with
      modifications based on culture results. Patients who died before D28 were
      classified as nonsurvivors. RESULTS: Of the 71 patients evaluated, 45 were
      classified as survivors. Of the 45 survivors, 35 (77.8%) received appropriate
      antimicrobial therapy, compared with 18 (69.2%) of the 26 nonsurvivors (p =
      0.57). On D0 and D4, the levels of all biomarkers (except CRP), as well as SOFA
      scores, were lower in eventual survivors than in eventual nonsurvivors. For D0
      and D4, the area under the ROC curve was largest for procalcitonin. On D0, MR
      proANP had the highest positive likelihood ratio (2.71) and positive predictive
      value (0.60), but procalcitonin had the highest negative predictive value (0.87).
      On D4, procalcitonin had the highest positive likelihood ratio (3.46), the
      highest positive predictive value (0.66), and the highest negative predictive
      value (0.93). CONCLUSIONS: The biomarkers procalcitonin, MR-proANP, and copeptin
      can predict mortality in VAP, as can the SOFA score. Procalcitonin alone has the
      greatest predictive power for such mortality.

PMID- 21881741
TI  - Retreatment of tuberculosis patients in the city of Porto Alegre, Brazil:
      outcomes.
AB  - OBJECTIVE: To describe the outcomes of retreatment in tuberculosis patients
      receiving the regimen known, in Brazil, as regimen 3 (streptomycin, ethambutol,
      ethionamide, and pyrazinamide for 3 months + ethambutol and ethionamide for 9
      months) after treatment failure with the basic regimen (rifampin, isoniazid, and
      pyrazinamide for 2 months + rifampin and isoniazid for 4 months). METHODS: A
      descriptive, uncontrolled, historical cohort study involving adult tuberculosis
      patients treated with regimen 3. We evaluated adverse drug effects, recurrence,
      treatment outcomes, and associated factors. RESULTS: The study included 229
      patients. The overall cure rate was 62%. For the patients who used the
      medications regularly and those who did not, the cure rate was 88% and 31%,
      respectively. Adverse events occurred in 95 patients (41.5%), and most of those
      events were related to the gastrointestinal tract. In the five-year follow-up
      period, relapse occurred in 17 cases (12.0%). CONCLUSIONS: Overall, the outcomes
      of treatment with regimen 3 were unsatisfactory, in part because this regimen was
      administered to a selected population of patients at high risk for noncompliance
      with treatment, as well as because it presents high rates of adverse effects,
      especially those related to the gastrointestinal tract, which might be caused by
      ethionamide. However, for those who took the medications regularly, the cure rate
      was satisfactory. The recurrence rate was higher than that recommended in
      international consensus guidelines, which might be attributable to the short (12
      month) treatment period. We believe that regimen 3, extended to 18 months,
      represents an option for patients with proven treatment compliance.

PMID- 21881742
TI  - Factors associated with delayed diagnosis of pulmonary tuberculosis in the state
      of Rio de Janeiro, Brazil.
AB  - OBJECTIVE: To estimate the total time elapsed between symptom onset and diagnosis
      of pulmonary tuberculosis (patient delay plus health care system delay),
      analyzing the factors associated with delayed diagnosis in the state of Rio de
      Janeiro, Brazil. METHODS: We conducted a questionnaire-based survey involving 218
      pulmonary tuberculosis patients treated for two months at 20 health care clinics
      and 3 hospitals in eight cities within the state of Rio de Janeiro. We collected
      socioeconomic and demographic data, as well as data regarding the health care
      system and the medical history of the patients. RESULTS: The median time elapsed
      from the onset of symptoms to diagnosis was 68 days (interquartile range [IQR]:
      35-119 days). The median patient delay (time from symptom onset to initial
      medical visit) was 30 days (IQR: 15-60 days), and the median health care system
      delay (time from initial medical visit to diagnosis) was 21 days (IQR: 8-47
      days). A cut-off point of 21 days was adopted. The factors independently
      associated with patient delay were female gender, cough, and unemployment
      [adjusted OR (95% CI) = 2.7 (1.3-5.6); 11.6 (2.3-58.8); and 2.0 (1.0-3.8),
      respectively], whereas only female gender was independently associated with
      health care system delay (OR= 3.2; 95% CI: 1.7-6.0). CONCLUSIONS: Delayed
      diagnosis of pulmonary tuberculosis remains a problem in Rio de Janeiro,
      increasing the risk of transmission and mortality, that risk being greater for
      women and the socioeconomically disadvantaged. Patients might not recognize the
      significance of chronic cough as a health problem. Tuberculosis education
      programs targeting women might improve this situation.

PMID- 21881743
TI  - Identification of nontuberculous mycobacteria isolated from clinical sterile
      sites in patients at a university hospital in the city of Rio de Janeiro, Brazil.
AB  - OBJECTIVE: To identify nontuberculous mycobacteria (NTM) isolated from sterile
      sites in patients hospitalized between 2001 and 2006 at the Clementino Fraga
      Filho University Hospital, located in the city of Rio de Janeiro, Brazil.
      METHODS: During the study period, 34 NTM isolates from sterile sites of 14
      patients, most of whom were HIV-positive, were submitted to phenotypic
      identification and hsp65 PCR-restriction enzyme analysis (PRA). RESULTS: Most
      isolates were identified as Mycobacterium avium, followed by M. monacense, M.
      kansasii, and M. abscessus. CONCLUSIONS: The combination of PRA, a relatively
      simple and inexpensive method, with the evaluation of a few phenotypic
      characteristics can allow NTM to be accurately identified in the routine of
      clinical laboratories.

PMID- 21881744
TI  - Pharmacological treatment of COPD.
AB  - Approximately seven million Brazilians over 40 years of age have COPD. In recent
      years, major advances have been made in the pharmacological treatment of this
      condition. We performed a systematic review including original articles on
      pharmacological treatments for COPD. We reviewed articles written in English,
      Spanish, or Portuguese; published between 2005 and 2009; and indexed in national
      and international databases. Articles with a sample size < 100 individuals were
      excluded. The outcome measures were symptoms, pulmonary function, quality of
      life, exacerbations, mortality, and adverse drug effects. Articles were
      classified in accordance with the Global Initiative for Chronic Obstructive Lung
      Disease criteria for the determination of the level of scientific evidence (grade
      of recommendation A, B, or C). Of the 84 articles selected, 40 (47.6%), 18
      (21.4%), and 26 (31.0%) were classified as grades A, B, and C, respectively. Of
      the 420 analyses made in these articles, 236 were regarding the comparison
      between medications and placebos. Among these 236 analyses, the most commonly
      studied medications (in 66, 48, and 42 analyses, respectively) were long-acting
      anticholinergics; the combination of long-acting beta(2) agonists and inhaled
      corticosteroids; and inhaled corticosteroids in isolation. Pulmonary function,
      adverse effects, and symptoms as outcomes generated 58, 54, and 35 analyses,
      respectively. The majority of the studies showed that the medications evaluated
      provided symptom relief; improved the quality of life and pulmonary function of
      patients; and prevented exacerbations. Few studies analyzed mortality as an
      outcome, and the role that pharmacological treatment plays in this outcome has
      yet to be fully defined. The medications studied are safe to use in the
      management of COPD and have few adverse effects.

PMID- 21881745
TI  - Pulmonary rehabilitation programs for patients with COPD.
AB  - Pulmonary rehabilitation programs are aimed at providing benefits to COPD
      patients, in various aspects. Our objective was to review the literature on COPD
      patient rehabilitation. This systematic review involved articles written in
      English, Spanish, or Portuguese; published between 2005 and 2009; and indexed in
      national and international databases. Articles were classified in accordance with
      the Global Initiative for Chronic Obstructive Lung Disease criteria for the
      determination of the level of scientific evidence (grade of recommendation A, B,
      or C). The outcome measures were exercise, quality of life, symptoms,
      exacerbations, mortality, and pulmonary function. Treatments were classified as
      standard rehabilitation, partial rehabilitation, strength exercises, and
      resistance exercises. Of the 40 articles selected, 4, 18, and 18 were classified
      as grades A, B, and C, respectively. Of the 181 analyses made in these articles,
      61, 50, 23, 23, 20, and 4, respectively, were related to the outcome measures
      quality of life, exercise, symptoms, exacerbations, pulmonary function, and
      mortality. The standard rehabilitation programs showed positive effects on all of
      the outcomes evaluated, except for mortality (because of the small number of
      analyses). However, we found no differences among the various rehabilitation
      programs regarding their effects on the outcomes studied. Rehabilitation programs
      can be considered important tools for the treatment of COPD. Therefore, health
      administrators should implement public policies including such programs in the
      routine of health care facilities.

PMID- 21881746
TI  - Cutaneous metastasis as the initial manifestation of lung adenocarcinoma.
AB  - We report the case of a 58-year-old male patient who was referred for oncology
      consultation due to an epigastric mass that had been growing rapidly for three
      months. Diagnostic investigation revealed that the mass was a metastasis of stage
      IV lung adenocarcinoma. The patient received five cycles of chemotherapy with
      cisplatin and gemcitabine as a first-line treatment, which was interrupted due to
      major adverse events. Although the pulmonary disease stabilized, the cutaneous
      disease progressed. The patient then received pemetrexed as a second-line
      chemotherapy, together with concurrent external radiotherapy, which was well
      tolerated. There was complete remission of the epigastric mass. However, the
      patient died three months after the treatment. Here, we emphasize the importance
      of a multidisciplinary approach and of its role in individualizing the treatment.

PMID- 21881747
TI  - Takotsubo cardiomyopathy triggered by beta(2) adrenergic agonist.

PMID- 21881748
TI  - Talc asbestosis and pulmonary tuberculosis in a patient exposed to the talc used
      in the production of soccer balls.

PMID- 21881749
TI  - Severe persistent asthma responsive to off-label use of omalizumab despite high
      and low levels of total serum IgE.

PMID- 21881751
TI  - Memorias do Instituto Oswaldo Cruz. Foreword.

PMID- 21881752
TI  - Recent advances in the study of avian malaria: an overview with an emphasis on
      the distribution of Plasmodium spp in Brazil.
AB  - Avian malaria parasites (Plasmodium) have a worldwide distribution except for
      Antarctica. They are transmitted exclusively by mosquito vectors (Diptera:
      Culicidae) and are of particular interest to health care research due to their
      phylogenetic relationship with human plasmodia and their ability to cause avian
      malaria, which is frequently lethal in non-adapted avian hosts. However,
      different features of avian Plasmodium spp, including their taxonomy and aspects
      of their life-history traits, need to be examined in more detail. Over the last
      10 years, ecologists, evolutionary biologists and wildlife researchers have
      recognized the importance of studying avian malaria parasites and other related
      haemosporidians, which are the largest group of the order Haemosporida by number
      of species. These studies have included understanding the ecological, behavioral
      and evolutionary aspects that arise in this wildlife host-parasite system.
      Molecular tools have provided new and exiting opportunities for such research.
      This review discusses several emerging topics related to the current research of
      avian Plasmodium spp and some related avian haemosporidians. We also summarize
      some important discoveries in this field and emphasize the value of using both
      polymerase chain reaction-based and microscopy-based methods in parallel for
      wildlife studies. We will focus on the genus Plasmodium, with an emphasis on the
      distribution and pathogenicity of these parasites in wild birds in Brazil.

PMID- 21881753
TI  - Molecular markers and genetic diversity of Plasmodium vivax.
AB  - Enhanced understanding of the transmission dynamics and population genetics for
      Plasmodium vivax is crucial in predicting the emergence and spread of novel
      parasite phenotypes with major public health implications, such as new relapsing
      patterns, drug resistance and increased virulence. Suitable molecular markers are
      required for these population genetic studies. Here, we focus on two groups of
      molecular markers that are commonly used to analyse natural populations of P.
      vivax. We use markers under selective pressure, for instance, antigen-coding
      polymorphic genes, and markers that are not under strong natural selection, such
      as most minisatellite and microsatellite loci. First, we review data obtained
      using genes encoding for P. vivax antigens: circumsporozoite protein, merozoite
      surface proteins 1 and 3alpha, apical membrane antigen 1 and Duffy binding
      antigen. We next address neutral or nearly neutral molecular markers, especially
      microsatellite loci, providing a complete list of markers that have already been
      used in P. vivax populations studies. We also analyse the microsatellite loci
      identified in the P. vivax genome project. Finally, we discuss some practical
      uses for P. vivax genotyping, for example, detecting multiple-clone infections
      and tracking the geographic origin of isolates.

PMID- 21881754
TI  - Analysis of the genetic variability of PvMSP-3alpha among Plasmodium vivax in
      Brazilian field isolates.
AB  - Reliable molecular markers are essential for a better understanding of the
      molecular epidemiology of Plasmodium vivax, which is a neglected human malaria
      parasite. The aim of this study was to analyze the genetic diversity of P. vivax
      isolates from the Brazilian Amazon using polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) analysis of the highly polymorphic
      merozoite surface protein-3alpha (PvMSP-3alpha) gene. To accomplish this, 60
      isolates of P. vivax from different endemic areas in the Brazilian Amazon were
      collected. The PvMSP-3alpha gene was amplified by nested-PCR. Three major types
      of the PvMSP-3alpha locus were detected at different frequencies: type A (68%), B
      (15%) and C (17%). A single sample showed two PCR fragments, which corresponded
      to infection with types A and C. PCR-RFLP analysis using the HhaI restriction
      enzyme for 52 isolates clearly identified 11 haplotypes, eight of which were from
      type A, two from type B and only one from type C. Seven other isolates did not
      show a clear pattern using PCR-RFLP. This result might be due to multiple clone
      infections. This study showed a high diversity of the PvMSP-3alpha gene among P.
      vivax isolates from the Brazilian Amazon, but also indicated that the detection
      performance of PCR-RFLP of the PvMSP-3alpha gene may not be sufficient to detect
      multiple clone infections.

PMID- 21881755
TI  - Antibodies against the Plasmodium falciparum glutamate-rich protein from
      naturally exposed individuals living in a Brazilian malaria-endemic area can
      inhibit in vitro parasite growth.
AB  - The glutamate-rich protein (GLURP) is an exoantigen expressed in all stages of
      the Plasmodium falciparum life cycle in humans. Anti-GLURP antibodies can inhibit
      parasite growth in the presence of monocytes via antibody-dependent cellular
      inhibition (ADCI), and a major parasite-inhibitory region has been found in the N
      terminal R0 region of the protein. Herein, we describe the antiplasmodial
      activity of anti-GLURP antibodies present in the sera from individuals naturally
      exposed to malaria in a Brazilian malaria-endemic area. The anti-R0 antibodies
      showed a potent inhibitory effect on the growth of P. falciparum in vitro, both
      in the presence (ADCI) and absence (GI) of monocytes. The inhibitory effect on
      parasite growth was comparable to the effect of IgGs purified from pooled sera
      from hyperimmune African individuals. Interestingly, in the ADCI test, higher
      levels of tumour necrosis factor alpha (TNF-alpha) were observed in the
      supernatant from cultures with higher parasitemias. Our data suggest that the
      antibody response induced by GLURP-R0 in naturally exposed individuals may have
      an important role in controlling parasitemia because these antibodies are able to
      inhibit the in vitro growth of P. falciparum with or without the cooperation from
      monocytes. Our results also indicate that TNF-alpha may not be relevant for the
      inhibitory effect on P. falciparum in vitro growth.

PMID- 21881756
TI  - Monoclonal auto-antibodies and sera of autoimmune patients react with Plasmodium
      falciparum and inhibit its in vitro growth.
AB  - The relationship between autoimmunity and malaria is not well understood. To
      determine whether autoimmune responses have a protective role during malaria, we
      studied the pattern of reactivity to plasmodial antigens of sera from 93 patients
      with 14 different autoimmune diseases (AID) who were not previously exposed to
      malaria. Sera from patients with 13 different AID reacted against Plasmodium
      falciparum by indirect fluorescent antibody test with frequencies varying from 33
      100%. In addition, sera from 37 AID patients were tested for reactivity against
      Plasmodium yoelii 17XNL and the asexual blood stage forms of three different P.
      falciparum strains. In general, the frequency of reactive sera was higher against
      young trophozoites than schizonts (p < 0.05 for 2 strains), indicating that the
      antigenic determinants targeted by the tested AID sera might be more highly
      expressed by the former stage. The ability of monoclonal auto-antibodies (auto
      Ab) to inhibit P. falciparum growth in vitro was also tested. Thirteen of the 18
      monoclonal auto-Ab tested (72%), but none of the control monoclonal antibodies,
      inhibited parasite growth, in some cases by greater than 40%. We conclude that
      autoimmune responses mediated by auto-Ab may present anti-plasmodial activity.

PMID- 21881757
TI  - Thrombocytopenia in malaria: who cares?
AB  - Despite not being a criterion for severe malaria, thrombocytopenia is one of the
      most common complications of both Plasmodium vivax and Plasmodium falciparum
      malaria. In a systematic review of the literature, platelet counts under
      150,000/mm3 ranged from 24-94% in patients with acute malaria and this frequency
      was not different between the two major species that affected humans. Minor
      bleeding is mentioned in case reports of patients with P. vivax infection and may
      be explained by medullary compensation with the release of mega platelets in the
      peripheral circulation by megakaryocytes, thus maintaining a good primary
      haemostasis. The speculated mechanisms leading to thrombocytopenia are:
      coagulation disturbances, splenomegaly, bone marrow alterations, antibody
      mediated platelet destruction, oxidative stress and the role of platelets as
      cofactors in triggering severe malaria. Data from experimental models are
      presented and, despite not being rare, there is no clear recommendation on the
      adequate management of this haematological complication. In most cases, a
      conservative approach is adopted and platelet counts usually revert to normal
      ranges a few days after efficacious antimalarial treatment. More studies are
      needed to specifically clarify if thrombocytopenia is the cause or consequence of
      the clinical disease spectrum.

PMID- 21881758
TI  - Pregnancy malaria: cryptic disease, apparent solution.
AB  - Malaria during pregnancy can be severe in non-immune women, but in areas of
      stable transmission, where women are semi-immune and often asymptomatic during
      infection, malaria is an insidious cause of disease and death for mothers and
      their offspring. Sequelae, such as severe anaemia and hypertension in the mother
      and low birth weight and infant mortality in the offspring, are often not
      recognised as consequences of infection. Pregnancy malaria, caused by Plasmodium
      falciparum, is mediated by infected erythrocytes (IEs) that bind to chondroitin
      sulphate A and are sequestered in the placenta. These parasites have a unique
      adhesion phenotype and distinct antigenicity, which indicates that novel targets
      may be required for development of an effective vaccine. Women become resistant
      to malaria as they acquire antibodies against placental IE, which leads to higher
      haemoglobin levels and heavier babies. Proteins exported from the placental
      parasites have been identified, including both variant and conserved antigens,
      and some of these are in preclinical development for vaccines. A vaccine that
      prevents P. falciparum malaria in pregnant mothers is feasible and would
      potentially save hundreds of thousands of lives each year.

PMID- 21881759
TI  - Biomarkers for susceptibility to infection and disease severity in human malaria.
AB  - Malaria remains a major infectious disease that affects millions of people. Once
      infected with Plasmodium parasites, a host can develop a broad range of clinical
      presentations, which result from complex interactions between factors derived
      from the host, the parasite and the environment. Intense research has focused on
      the identification of reliable predictors for exposure, susceptibility to
      infection and the development of severe complications during malaria. Although
      most promising markers are based on the current understanding of malaria
      immunopathogenesis, some are also focused more broadly on mechanisms of tissue
      damage and inflammation. Taken together, these markers can help optimise
      therapeutic strategies and reduce disease burden. Here, we review the recent
      advances in the identification of malarial biomarkers, focusing on those related
      to parasite exposure and disease susceptibility. We also discuss priorities for
      research in biomarkers for severe malaria.

PMID- 21881760
TI  - On cytoadhesion of Plasmodium vivax: raison d'etre?
AB  - It is generally accepted that Plasmodium vivax, the most widely distributed human
      malaria parasite, causes mild disease and that this species does not sequester in
      the deep capillaries of internal organs. Recent evidence, however, has
      demonstrated that there is severe disease, sometimes resulting in death,
      exclusively associated with P. vivax and that P. vivax-infected reticulocytes are
      able to cytoadhere in vitro to different endothelial cells and placental
      cryosections. Here, we review the scarce and preliminary data on cytoadherence in
      P. vivax, reinforcing the importance of this phenomenon in this species and
      highlighting the avenues that it opens for our understanding of the pathology of
      this neglected human malaria parasite.

PMID- 21881761
TI  - Surface-expressed enolases of Plasmodium and other pathogens.
AB  - Enolase is the eighth enzyme in the glycolytic pathway, a reaction that generates
      ATP from phosphoenol pyruvate in cytosolic compartments. Enolase is essential,
      especially for organisms devoid of the Krebs cycle that depend solely on
      glycolysis for energy. Interestingly, enolase appears to serve a separate
      function in some organisms, in that it is also exported to the cell surface via a
      poorly understood mechanism. In these organisms, surface enolase assists in the
      invasion of their host cells by binding plasminogen, an abundant plasma protease
      precursor. Binding is mediated by the interaction between a lysine motif of
      enolase with Kringle domains of plasminogen. The bound plasminogen is then
      cleaved by specific proteases to generate active plasmin. Plasmin is a potent
      serine protease that is thought to function in the degradation of the
      extracellular matrix surrounding the targeted host cell, thereby facilitating
      pathogen invasion. Recent work revealed that the malaria parasite Plasmodium also
      expresses surface enolase, and that this feature may be essential for completion
      of its life cycle. The therapeutic potential of targeting surface enolases of
      pathogens is discussed.

PMID- 21881763
TI  - The prospect of eliminating malaria transmission in some regions of Brazil.
AB  - This paper discusses malaria epidemiology and control in Brazil as well as the
      prospect of interrupting transmission in some areas of the country. The concepts
      of receptivity and vulnerability of an area to malaria transmission are analysed
      to predict where elimination might occur in a near future. Outside of the Amazon
      Region and in the oriental states of the Amazon, such as Tocantins, Maranhao and
      Mato Grosso, it is likely that malaria transmission can be eliminated with the
      development and sustained use of a good surveillance system.

PMID- 21881764
TI  - Predictors of local malaria outbreaks: an approach to the development of an early
      warning system in Colombia.
AB  - Risk factor surveillance is a complementary tool of morbidity and mortality
      surveillance that improves the likelihood that public health interventions are
      implemented in a timely fashion. The aim of this study was to identify population
      predictors of malaria outbreaks in endemic municipalities of Colombia with the
      goal of developing an early warning system for malaria outbreaks. We conducted a
      multiple-group, exploratory, ecological study at the municipal level. Each of the
      290 municipalities with endemic malaria that we studied was classified according
      to the presence or absence of outbreaks. The measurement of variables was based
      on historic registries and logistic regression was performed to analyse the data.
      Altitude above sea level [odds ratio (OR) 3.65, 95% confidence interval (CI) 1.34
      9.98], variability in rainfall (OR 1.85, 95% CI 1.40-2.44) and the proportion of
      inhabitants over 45 years of age (OR 0.17, 95% CI 0.08-0.38) were factors
      associated with malaria outbreaks in Colombian municipalities. The results
      suggest that environmental and demographic factors could have a significant
      ability to predict malaria outbreaks on the municipal level in Colombia. To
      advance the development of an early warning system, it will be necessary to
      adjust and standardise the collection of required data and to evaluate the
      accuracy of the forecast models.

PMID- 21881762
TI  - Malaria-related anaemia: a Latin American perspective.
AB  - Malaria is the most important parasitic disease worldwide, responsible for an
      estimated 225 million clinical cases each year. It mainly affects children,
      pregnant women and non-immune adults who frequently die victims of cerebral
      manifestations and anaemia. Although the contribution of the American continent
      to the global malaria burden is only around 1.2 million clinical cases annually,
      there are 170 million inhabitants living at risk of malaria transmission in this
      region. On the African continent, where Plasmodium falciparum is the most
      prevalent human malaria parasite, anaemia is responsible for about half of the
      malaria-related deaths. Conversely, in Latin America (LA), malaria-related
      anaemia appears to be uncommon, though there is a limited knowledge about its
      real prevalence. This may be partially explained by several factors, including
      that the overall malaria burden in LA is significantly lower than that of Africa,
      that Plasmodium vivax, the predominant Plasmodium species in the region, appears
      to display a different clinical spectrus and most likely because better health
      services in LA prevent the development of severe malaria cases. With the aim of
      contributing to the understanding of the real importance of malaria-related
      anaemia in LA, we discuss here a revision of the available literature on the
      subject and the usefulness of experimental animal models, including New World
      monkeys, particularly for the study of the mechanisms involved in the
      pathogenesis of malaria.

PMID- 21881765
TI  - Epidemiology and control of malaria in Colombia.
AB  - Malaria is currently one of the most serious public health problems in Colombia
      with an endemic/epidemic transmission pattern that has maintained endemic levels
      and an average of 105,000 annual clinical cases being reported over the last five
      years. Plasmodium vivax accounts for approximately 70% of reported cases with the
      remainder attributed almost exclusively to Plasmodium falciparum. A limited
      number of severe and complicated cases have resulted in mortality, which is a
      downward trend that has been maintained over the last few years. More than 90% of
      the malaria cases in Colombia are confined to 70 municipalities (about 7% of the
      total municipalities of Colombia), with high predominance (85%) in rural areas.
      The purpose of this paper is to review the progress of malaria-eradication
      activities and control measures over the past century within the eco
      epidemiologic context of malaria transmission together with official consolidated
      morbidity and mortality reports. This review may contribute to the formulation of
      new antimalarial strategies and policies intended to achieve malaria
      elimination/eradication in Colombia and in the region.

PMID- 21881766
TI  - Sentinel network for monitoring in vitro susceptibility of Plasmodium falciparum
      to antimalarial drugs in Colombia: a proof of concept.
AB  - Drug resistance is one of the principal obstacles blocking worldwide malaria
      control. In Colombia, malaria remains a major public health concern and drug
      resistant parasites have been reported. In vitro drug susceptibility assays are a
      useful tool for monitoring the emergence and spread of drug-resistant Plasmodium
      falciparum. The present study was conducted as a proof of concept for an
      antimalarial drug resistance surveillance network based on in vitro
      susceptibility testing in Colombia. Sentinel laboratories were set up in three
      malaria endemic areas. The enzyme linked immunosorbent assay-histidine rich
      protein 2 and schizont maturation methods were used to assess the susceptibility
      of fresh P. falciparum isolates to six antimalarial drugs. This study
      demonstrates that an antimalarial drug resistance surveillance network based on
      in vitro methods is feasible in the field with the participation of a research
      institute, local health institutions and universities. It could also serve as a
      model for a regional surveillance network. Preliminary susceptibility results
      showed widespread chloroquine resistance, which was consistent with previous
      reports for the Pacific region. However, high susceptibility to
      dihydroartemisinin and lumefantrine compounds, currently used for treatment in
      the country, was also reported. The implementation process identified critical
      points and opportunities for the improvement of network sustainability
      strategies.

PMID- 21881767
TI  - Change in mutation patterns of Plasmodium vivax dihydrofolate reductase (Pvdhfr)
      and dihydropteroate synthase (Pvdhps) in P. vivax isolates from malaria endemic
      areas of Thailand.
AB  - Malaria is the most important public health problem in several countries. In
      Thailand, co-infections of Plasmodium vivax and Plasmodium falciparum are common.
      We examined the prevalence and patterns of mutations in P. vivax dihydrofolate
      reductase (Pvdhfr) and P. vivax dihydropteroate synthase (Pvdhps) in 103 blood
      samples collected from patients with P. vivax infection who had attended the
      malaria clinic in Mae Sot, Tak Province during 2009 and 2010. Using nested
      polymerase chain reaction-restriction fragment length polymorfism, we examined
      single nucleotide polymorphisms-haplotypes at amino acid positions 13, 33, 57,
      58, 61, 117 and 173 of Pvdhfr and 383 and 553 of Pvdhps. All parasite isolates
      carried mutant Pvdhfr alleles, of which the most common alleles were triple
      mutants (99%). Eight different types of Pvdhfr and combination alleles were
      found, as follows: 57I/58R/117T, 57I/58R/117T, 57I/58R/117T/N, 57L/58R/117T,
      57L/58R/117T, 58R/61M/117N, 58R/61M/117N and 13L/57L/58R/117T. The most common
      Pvdhfr alleles were 57I/58R/117T (77.7%), 57I/58R/117T/N (1%), 57L/58R/117T
      (5.8%) and 58R/61M/117N (14.5%). The most common Pvdhfr alleles were 57I/58R/117T
      (77.7%), 57I/58R/117T/N (1%), 57L/58R/117T (5.8%) and 58R/61M/117N (14.5%).
      Additionally, we recovered one isolate of a carrying a quadruple mutant allele,
      13L/57L/58R/117T. The most prevalent Pvdhps allele was a single mutation in amino
      acid 383 (82.5%), followed by the wild-type A383/A553 (17.5%) allele. Results
      suggest that all P. vivax isolates in Thailand carry some combination of
      mutations in Pvdhfr and Pvdhps. Our findings demonstrate that development of new
      antifolate drugs effective against sulfadoxine-pyrimethamine-resistant P. vivax
      is required.

PMID- 21881768
TI  - Isoprenoid biosynthesis in the erythrocytic stages of Plasmodium falciparum.
AB  - The development of new drugs is one strategy for malaria control. Biochemical
      pathways localised in the apicoplast of the parasite, such as the synthesis of
      isoprenic precursors, are excellent targets because they are different or absent
      in the human host. Isoprenoids are a large and highly diverse group of natural
      products with many functions and their synthesis is essential for the parasite's
      survival. During the last few years, the genes, enzymes, intermediates and
      mechanisms of this biosynthetic route have been elucidated. In this review, we
      comment on some aspects of the methylerythritol phosphate pathway and discuss the
      presence of diverse isoprenic products such as dolichol, ubiquinone, carotenoids,
      menaquinone and isoprenylated proteins, which are biosynthesised during the
      intraerythrocytic stages of Plasmodium falciparum.

PMID- 21881769
TI  - A review of antimalarial plants used in traditional medicine in communities in
      Portuguese-speaking countries: Brazil, Mozambique, Cape Verde, Guinea-Bissau, Sao
      Tome and Principe and Angola.
AB  - The isolation of bioactive compounds from medicinal plants, based on traditional
      use or ethnomedical data, is a highly promising potential approach for
      identifying new and effective antimalarial drug candidates. The purpose of this
      review was to create a compilation of the phytochemical studies on medicinal
      plants used to treat malaria in traditional medicine from the Community of
      Portuguese-Speaking Countries (CPSC): Angola, Brazil, Cape Verde, Guinea-Bissau,
      Mozambique and Sao Tome and Principe. In addition, this review aimed to show that
      there are several medicinal plants popularly used in these countries for which
      few scientific studies are available. The primary approach compared the
      antimalarial activity of native species used in each country with its extracts,
      fractions and isolated substances. In this context, data shown here could be a
      tool to help researchers from these regions establish a scientific and technical
      network on the subject for the CPSC where malaria is a public health problem.

PMID- 21881770
TI  - Chemoresistance of Plasmodium falciparum and Plasmodium vivax parasites in
      Brazil: consequences on disease morbidity and control.
AB  - In Brazil, malaria still remains a clinically important febrile syndrome for
      local populations and travelers, occurring mostly in the Amazon Basin. This
      review aims to report the main efforts employed to control this disease since the
      1940s and the emergence of Plasmodium falciparum and Plasmodium vivax
      chemoresistance to chloroquine and sulphadoxine-pyrimethamine among other drugs.
      Additionally, in vivo, in vitro and molecular studies as well as malaria
      chemoresistance consequences on disease morbidity and policy treatment guidelines
      were commented.

PMID- 21881771
TI  - TLR5-dependent immunogenicity of a recombinant fusion protein containing an
      immunodominant epitope of malarial circumsporozoite protein and the FliC
      flagellin of Salmonella Typhimurium.
AB  - Recently, we described the improved immunogenicity of new malaria vaccine
      candidates based on the expression of fusion proteins containing immunodominant
      epitopes of merozoites and Salmonella enterica serovar Typhimurium flagellin
      (FliC) protein as an innate immune agonist. Here, we tested whether a similar
      strategy, based on an immunodominant B-cell epitope from malaria sporozoites,
      could also generate immunogenic fusion polypeptides. A recombinant His6-tagged
      FliC protein containing the C-terminal repeat regions of the VK210 variant of
      Plasmodium vivax circumsporozoite (CS) protein was constructed. This recombinant
      protein was successfully expressed in Escherichia coli as soluble protein and was
      purified by affinity to Ni-agarose beads followed by ion exchange chromatography.
      A monoclonal antibody specific for the CS protein of P. vivax sporozoites (VK210)
      was able to recognise the purified protein. C57BL/6 mice subcutaneously immunised
      with the recombinant fusion protein in the absence of any conventional adjuvant
      developed protein-specific systemic antibody responses. However, in mice
      genetically deficient in expression of TLR5, this immune response was extremely
      low. These results extend our previous observations concerning the immunogenicity
      of these recombinant fusion proteins and provide evidence that the main mechanism
      responsible for this immune activation involves interactions with TLR5, which has
      not previously been demonstrated for any recombinant FliC fusion protein.

PMID- 21881772
TI  - Induction and maintenance of protective CD8+ T cells against malaria liver
      stages: implications for vaccine development.
AB  - CD8+ T cells against malaria liver stages represent a major protective immune
      mechanism against infection. Following induction in the peripheral lymph nodes by
      dendritic cells (DCs), these CD8+ T cells migrate to the liver and eliminate
      parasite infected hepatocytes. The processing and presentation of sporozoite
      antigen requires TAP mediated transport of major histocompatibility complex class
      I epitopes to the endoplasmic reticulum. Importantly, in DCs this process is also
      dependent on endosome-mediated cross presentation while this mechanism is not
      required for epitope presentation on hepatocytes. Protective CD8+ T cell
      responses are strongly dependent on the presence of CD4+ T cells and the capacity
      of sporozoite antigen to persist for a prolonged period of time. While human
      trials with subunit vaccines capable of inducing antibodies and CD4+ T cell
      responses have yielded encouraging results, an effective anti-malaria vaccine
      will likely require vaccine constructs designed to induce protective CD8+ T cells
      against malaria liver stages.

PMID- 21881774
TI  - Synergism/complementarity of recombinant adenoviral vectors and other vaccination
      platforms during induction of protective immunity against malaria.
AB  - The lack of immunogenicity of most malaria antigens and the complex immune
      responses required for achieving protective immunity against this infectious
      disease have traditionally hampered the development of an efficient human malaria
      vaccine. The current boom in development of recombinant viral vectors and their
      use in prime-boost protocols that result in enhanced immune outcomes have
      increased the number of malaria vaccine candidates that access pre-clinical and
      clinical trials. In the frontline, adenoviruses and poxviruses seem to be giving
      the best immunization results in experimental animals and their mutual
      combination, or their combination with recombinant proteins (formulated in
      adjuvants and given in sequence or being given as protein/virus admixtures), has
      been shown to reach unprecedented levels of anti-malaria immunity that
      predictably will be somehow reproduced in the human setting. However, all this
      optimism was previously seen in the malaria vaccine development field without
      many real applicable results to date. We describe here the current state-of-the
      art in the field of recombinant adenovirus research for malaria vaccine
      development, in particular referring to their use in combination with other
      immunogens in heterologous prime-boost protocols, while trying to simultaneously
      show our contributions and point of view on this subject.

PMID- 21881773
TI  - Platform for Plasmodium vivax vaccine discovery and development.
AB  - Plasmodium vivax is the most prevalent malaria parasite on the American
      continent. It generates a global burden of 80-100 million cases annually and
      represents a tremendous public health problem, particularly in the American and
      Asian continents. A malaria vaccine would be considered the most cost-effective
      measure against this vector-borne disease and it would contribute to a reduction
      in malaria cases and to eventual eradication. Although significant progress has
      been achieved in the search for Plasmodium falciparum antigens that could be used
      in a vaccine, limited progress has been made in the search for P. vivax
      components that might be eligible for vaccine development. This is primarily due
      to the lack of in vitro cultures to serve as an antigen source and to inadequate
      funding. While the most advanced P. falciparum vaccine candidate is currently
      being tested in Phase III trials in Africa, the most advanced P. vivax candidates
      have only advanced to Phase I trials. Herein, we describe the overall strategy
      and progress in P. vivax vaccine research, from antigen discovery to preclinical
      and clinical development and we discuss the regional potential of Latin America
      to develop a comprehensive platform for vaccine development.

PMID- 21881776
TI  - Can Wolbachia be used to control malaria?
AB  - Malaria is a mosquito-borne infectious disease caused by Plasmodium parasites
      transmitted by the infectious bite of Anopheles mosquitoes. Vector control of
      malaria has predominantly focused on targeting the adult mosquito through
      insecticides and bed nets. However, current vector control methods are often not
      sustainable for long periods so alternative methods are needed. A novel
      biocontrol approach for mosquito-borne diseases has recently been proposed, it
      uses maternally inherited endosymbiotic Wolbachia bacteria transinfected into
      mosquitoes in order to interfere with pathogen transmission. Transinfected
      Wolbachia strains in Aedes aegypti mosquitoes, the primary vector of dengue
      fever, directly inhibit pathogen replication, including Plasmodium gallinaceum,
      and also affect mosquito reproduction to allow Wolbachia to spread through
      mosquito populations. In addition, transient Wolbachia infections in Anopheles
      gambiae significantly reduce Plasmodium levels. Here we review the prospects of
      using a Wolbachia-based approach to reduce human malaria transmission through
      transinfection of Anopheles mosquitoes.

PMID- 21881777
TI  - Molecular divergence in the timeless and cpr genes among three sympatric cryptic
      species of the Anopheles triannulatus complex.
AB  - Anopheles triannulatus s.l. is a malaria vector with a wide geographic
      distribution, ranging from Argentina-Nicaragua and Trinidad. Here we analysed
      sequences of two genes, timeless and cpr, to assess the genetic variability and
      divergence among three sympatric cryptic species of this complex from Salobra,
      central-western Brazil. The timeless gene sequences did not conclusively
      differentiate Anopheles halophylus and An. triannulatus species "C". However, a
      partial separation has been observed between these species and An. triannulatus
      s.s. Importantly, the analysis of the cpr gene sequences revealed fixed
      differences, no shared polymorphisms and considerable genetic differentiation
      among the three species of the An. triannulatus complex. The results confirm that
      An. triannulatus s.s., An. halophylus and An. triannulatus species C are distinct
      taxa, with the latter two likely representing a more recent speciation event.

PMID- 21881775
TI  - Malaria transmission blocking immunity and sexual stage vaccines for interrupting
      malaria transmission in Latin America.
AB  - Malaria is a vector-borne disease that is considered to be one of the most
      serious public health problems due to its high global mortality and morbidity
      rates. Although multiple strategies for controlling malaria have been used, many
      have had limited impact due to the appearance and rapid dissemination of mosquito
      resistance to insecticides, parasite resistance to multiple antimalarial drug,
      and the lack of sustainability. Individuals in endemic areas that have been
      permanently exposed to the parasite develop specific immune responses capable of
      diminishing parasite burden and the clinical manifestations of the disease,
      including blocking of parasite transmission to the mosquito vector. This is
      referred to as transmission blocking (TB) immunity (TBI) and is mediated by
      specific antibodies and other factors ingested during the blood meal that inhibit
      parasite development in the mosquito. These antibodies recognize proteins
      expressed on either gametocytes or parasite stages that develop in the mosquito
      midgut and are considered to be potential malaria vaccine candidates. Although
      these candidates, collectively called TB vaccines (TBV), would not directly stop
      malaria from infecting individuals, but would stop transmission from infected
      person to non-infected person. Here, we review the progress that has been
      achieved in TBI studies and the development of TBV and we highlight their
      potential usefulness in areas of low endemicity such as Latin America.

PMID- 21881779
TI  - Habitat suitability of Anopheles vector species and association with human
      malaria in the Atlantic Forest in south-eastern Brazil.
AB  - Every year, autochthonous cases of Plasmodium vivax malaria occur in low
      endemicity areas of Vale do Ribeira in the south-eastern part of the Atlantic
      Forest, state of Sao Paulo, where Anopheles cruzii and Anopheles bellator are
      considered the primary vectors. However, other species in the subgenus
      Nyssorhynchus of Anopheles (e.g., Anopheles marajoara) are abundant and may
      participate in the dynamics of malarial transmission in that region. The
      objectives of the present study were to assess the spatial distribution of An.
      cruzii, An. bellator and An. marajoara and to associate the presence of these
      species with malaria cases in the municipalities of the Vale do Ribeira.
      Potential habitat suitability modelling was applied to determine both the spatial
      distribution of An. cruzii, An. bellator and An. marajoara and to establish the
      density of each species. Poisson regression was utilized to associate malaria
      cases with estimated vector densities. As a result, An. cruzii was correlated
      with the forested slopes of the Serra do Mar, An. bellator with the coastal plain
      and An. marajoara with the deforested areas. Moreover, both An. marajoara and An.
      cruzii were positively associated with malaria cases. Considering that An.
      marajoara was demonstrated to be a primary vector of human Plasmodium in the
      rural areas of the state of Amapa, more attention should be given to the species
      in the deforested areas of the Atlantic Forest, where it might be a secondary
      vector.

PMID- 21881780
TI  - Population parameters of the endangered titi monkey, Callicebus coimbrai
      Kobayashi and Langguth, 1999, in the fragmented landscape of southern Sergipe,
      Brazil.
AB  - The recently-discovered titi, Callicebus coimbrai, is endemic to the coastal
      Brazilian Atlantic Forest south of the Sao Francisco River, a region with a long
      tradition of deforestation. While a number of C. coimbrai populations have now
      been identified, little is known about basic population parameters. Considering
      the importance of this information for conservation planning, the population of a
      site in southern Sergipe (with a total area of forest of approximately 500 ha)
      was surveyed between April and October 2008. Standard line transect procedures
      were used in the four largest fragments, and additional monitoring included the
      use of playback broadcasts for the observation of titi groups. The presence of
      titis was confirmed in all the forest fragments at the site, including one of
      only five hectares. Two other primates - Callithrix jacchus and Cebus
      xanthosternos - were also recorded at the site, but were less abundant than
      titis. A total transect walk of 476 km provided 164 sightings of primates, the
      majority of which (104) were of Callicebus coimbrai. Titi groups ranged in size
      between two and five individuals. The most reliable estimate of overall
      population density, derived from the combined data set, was 12.6 individuals per
      km2;, although density was much higher in smaller (more disturbed) fragments. The
      total population of Callicebus coimbrai at the site was estimated to be at least
      50 individuals, which may represent a considerable proportion of the population
      of the species remaining in the wild. In addition to its apparent tolerance of
      habitat fragmentation, densities of C. coimbrai recorded at the site compare
      favourably with those of other Atlantic Forest titi species.

PMID- 21881778
TI  - Malaria vector species in Colombia: a review.
AB  - Here we present a comprehensive review of the literature on the vectorial
      importance of the major Anopheles malaria vectors in Colombia. We provide basic
      information on the geographical distribution, altitudinal range, immature
      habitats, adult behaviour, feeding preferences and anthropophily, endophily and
      infectivity rates. We additionally review information on the life cycle,
      longevity and population fluctuation of Colombian Anopheles species. Emphasis was
      placed on the primary vectors that have been epidemiologically incriminated in
      malaria transmission: Anopheles darlingi, Anopheles albimanus and Anopheles
      nuneztovari. The role of a selection of local, regional or secondary vectors
      (e.g., Anopheles pseudopunctipennis and Anopheles neivai) is also discussed. We
      highlight the importance of combining biological, morphological and molecular
      data for the correct taxonomical determination of a given species, particularly
      for members of the species complexes. We likewise emphasise the importance of
      studying the bionomics of primary and secondary vectors along with an examination
      of the local conditions affecting the transmission of malaria. The presence and
      spread of the major vectors and the emergence of secondary species capable of
      transmitting human Plasmodia are of great interest. When selecting control
      measures, the anopheline diversity in the region must be considered. Variation in
      macroclimate conditions over a species' geographical range must be well
      understood and targeted to plan effective control measures based on the
      population dynamics of the local Anopheles species.

PMID- 21881781
TI  - Effect of environmental quality and mesohabitat structure on a Biotic Integrity
      Index based on fish assemblages of cerrado streams from Rio Cuiaba basin, Brazil.
AB  - Over the last 30 years, the Cerrado has been experiencing various antropic
      impacts that have brought about alterations to species composition, structure and
      functioning of aquatic habitats. Therefore, studies on negative impacts are
      useful to prevent future damage and restore environmental quality. The objectives
      of our study were: i) to adapt an index of biotic integrity of streams in the Rio
      Cuiaba Basin and ii) to analyze if the Index of Biotic Integrity (IBI) correlated
      with the environmental quality measured by the Index of Environmental Quality
      (IEQ) and with the mesohabitat structure. We sampled 26 streams in sub-basins of
      the Cuiaba River. In each stream, we closed a stretch of 50 m with blockage nets
      and used electrofishing to capture fish. To obtain a measure of environmental
      quality in sampled units, we characterized the stream and its micro basin. For
      the analyses, we used the Spearman Correlation, Kruskal-Wallis test and Analysis
      of Multiple Regression. We collected 697 individuals distributed into 6 orders,
      15 families and 49 species. The IBI followed changes on environmental quality
      measured by IEQ when we removed streams that present natural barriers from the
      analysis (r2 = 0.4; r2 = 0.58). Types of land use did not affect the biotic
      integrity (n = 26; df = 4; H = 4,860; p = 0.302), but natural and artificial
      barriers affected it (n = 26; df = 4; H = 11,027; p = 0.026). The IBI was not
      sensitive to variations in mesohabitat structure (F2,23 = 0.373; r2 = 0.031; Axe
      1 p = 0.620; Axe 2 p = 0.490). The IBI is certainly a reasonable instrument for
      evaluating changes in the environment, but we cannot ignore the fact that we were
      able to obtain the same result with any combinations of metrics. This makes its
      analysis and interpretation difficult.

PMID- 21881782
TI  - Structure of the phytoplankton community in the Cachoeira Dourada reservoir
      (GO/MG), Brazil.
AB  - The limnological features and the phytoplankton community of the Cachoeira
      Dourada reservoir were analyzed in December 2006, May 2007 and November 2007.
      Temporal changes in the taxonomic composition, density, diversity and dominance
      of species were analyzed in relation to climatic factors and the physical and
      chemical characteristics of the water. A positive correlation was found between
      some of the physical and chemical variables and the phytoplankton community.
      According to the CCA, variables such as the extent of the euphotic zone,
      temperature, pH, nitrogen and phosphorus concentrations directly affected the
      phytoplankton dynamics. Organisms belonging to the class Cyanophyceae were the
      most representative in all the sampling periods, comprising the functional groups
      K, S1, M and H. Hydrodynamics and seasonal fluctuations of environmental factors
      were the driving forces determining the composition and abundance of the algal
      assemblages. Despite the prevalence of Cyanobacteria, the reservoir is still
      oligotrophic. The absence of blooms and the relatively low population abundances
      indicated that the quality of the reservoir's water still lies within the limits
      required for its multiples uses.

PMID- 21881783
TI  - Water quality changes in floodplain lakes due to the Amazon River flood pulse:
      Lago Grande de Curuai (Para).
AB  - Assurance of water quality for human consumption is essential for public health
      policies. In the Amazon floodplain, the seasonal water level variation causes
      periodic flooding of marginal areas that are usually used for settlements,
      agriculture and livestock. Therefore, the exchange of materials between the
      terrestrial and aquatic ecosystem affects the proportion of suspended and
      dissolved components in water and its physical-chemical characteristics, and
      consequently the quality of the water used by local people. Following this
      approach, the aim of this study is to evaluate changes in water quality in Lago
      Grande de Curuai floodplain, Obidos, Para in response to the flood pulse, during
      one hydrological year from 2003 to 2004, based on water use classes (according to
      National Water Agency 357/2005 resolution) using chlorophyll-a and dissolved
      oxygen concentration as parameters and the eutrophication index. Ordinary kriging
      was applied to interpolate chlorophyll-a and dissolved oxygen and to predict
      values at non sampled locations. Each location was then classified according to
      water use acceptable parameters and to Carlson Trophic State Index modified by
      Toledo to map lake water classes and trophic status. The result showed that Lago
      Grande de Curuai floodplain is a supereutrophic system, with levels of dissolved
      oxygen and chlorophyll-a not suitable for human supply during the receding water
      phase. These areas are located near the riverine communities, which can cause
      health problems due to the presence of potentially toxic algae. Therefore,
      monitoring water quality in Amazon lakes is essential to ensure the availability
      has appropriate quality for human and animal supplies.

PMID- 21881784
TI  - The hummingbird community and their floral resources in an urban forest remnant
      in Brazil.
AB  - The temporal and spatial resource use among hummingbirds was studied over 13
      months in an urban forest remnant (Prosa State Park: PSP) in Campo Grande, Mato
      Grosso do Sul, Brazil. Hummingbird visitation was recorded at three
      ornithophilous and eleven non-ornithophilous species. Flower density was roughly
      constant during the study period, with the density of non-ornithophilous flowers
      being higher than that of ornithophilous ones. Mean values of nectar volume and
      concentration were similar between ornithophilous and non-ornithophilous species.
      Eight hummingbird species were observed at PSP: Amazilia fimbriata,
      Anthracothorax nigricollis, Chlorostilbon lucidus, Eupetomena macroura,
      Hylocharis chrysura, Florisuga fusca, Thalurania furcata and an unidentified
      species. Hummingbird visit frequencies to ornithophilous and non-ornithophilous
      flowers were similar. However, some non-ornithophilous species received a higher
      number of visits, which seems to be related to their large number of open flowers
      per plant per day. The number of feedings bouts of hummingbirds increased with
      the total number of flowers observed per focal plant. All recorded species of
      hummingbirds visited non-ornithophilous flowers, predominantly melittophilous and
      generalised entomophilous flowers. Hummingbird species recorded at PSP may be
      viewed as generalists, visiting a large number of non-ornithophilous species.
      Despite being an urban forest, PSP is relatively rich in hummingbird species,
      suggesting that it provides important shelter and foraging sites for hummingbirds
      in such an environment.

PMID- 21881785
TI  - Ectoparasites as numerical dominant species in parasite community of
      Trachelyopterus striatulus (Siluriformes: Auchenipteridae) from Guandu River,
      southeastern Brazil.
AB  - Sixty specimens of singing catfish Trachelyopterus striatulus (Steindachner,
      1877) (Siluriformes: Auchenipteridae) collected from Guandu River (22o 48' 32" S
      and 43o 37' 35" W), in the state of Rio de Janeiro, Brazil from October 2006 to
      March 2009, were necropsied to study their parasites. From the 60 specimens of T.
      striatulus examined 57 were parasitised by at least one parasite species. The
      majority of the parasite specimens collected were monogeneans followed by
      Nematoda, Digenea and Hirudinea. Cosmetocleithrum sp. was the numerically
      predominant species with highest prevalence and abundance. The parasites of T.
      striatulus showed the typical pattern of aggregated distribution. No parasite
      species showed significant correlation between the body total length of the host
      and their abundance. The mean parasite species richness was not correlated with
      the host's total body length and sex. Values of the Brillouin index of diversity
      had a mean of H = 0.083 +/- 0.136.

PMID- 21881786
TI  - A new occurrence of Anodontites tenebricosus (Bivalvia: Mycetopodidae) in the
      Sapucai river basin, Sao Paulo, Brazil: environmental and conchological aspects.
AB  - The aim of this work was to register the occurrence of Anodontites tenebricosus
      (Bivalvia: Mycetopodidae) in the Sapucai river basin, municipality of Sao Joaquim
      da Barra, Sao Paulo state, Brazil, associating its occurrence to the environment
      in which they are found, besides providing conchological data to contribute to
      the identification of the species. Fifty one specimens of Anodontites
      tenebricosus were studied regarding their conchological and morphometrical
      aspects. Strong correlations were found between the morphometric variables, the
      correlation between 'length and height of the shell' being the most significant.
      The characteristics of the shells of A. tenebricosus found in the Sapucai river
      basin resemble the descriptions of the species found in the literature;
      therefore, we are able to expand the area of occurrence of the species for the
      state of Sao Paulo.

PMID- 21881787
TI  - Effects of flow reduction and spillways on the composition and structure of
      benthic macroinvertebrate communities in a Brazilian river reach.
AB  - Dams are a major threat to aquatic biological diversity. By altering the natural
      flow of rivers, dams modify fluvial habitats, making them unsuitable for the
      growth and reproduction of many aquatic species. The aim of this study was to
      evaluate the effects of a reduced flow reach (RFR) on benthic macroinvertebrate
      communities. Benthic macroinvertebrates were collected at six sites downstream of
      the Amador Aguiar Power Plant I before (lotic phase) and after (semi-lentic
      phase) Araguari River mean flow was reduced from 346 to 7 m3.s-1. Changes in
      macroinvertebrates richness, diversity and total biomass were not observed.
      Ablabesmyia, Tanytarsus (Chironomidae, Diptera), Leptoceridae and
      Polycentropodidae (Trichoptera) densities significantly increased the first year
      after flow reduction and the construction of spillways (t-test; p < 0.05). An
      analysis of similarity (ANOSIM) showed statistical differences in taxonomical
      composition despite considerable overlap in communities between the lotic and
      semi-lentic phases (R = 0.3; p < 0.01). In both phases, the macroinvertebrates
      were characterised by the dominance of groups tolerant to human disturbance
      (e.g., Chironomidae, Ceratopogonidae and Oligochaeta) and by the presence of the
      alien bivalve species Corbicula fluminea (Veneroidae), suggesting that the river
      was already degraded before the hydraulic modifications. Since the 1980s, the
      Araguari River has been continuously subjected to human pressures (e.g., cascade
      dams, urbanization and replacement of native vegetation by pasture and crops).
      These activities have led to impoverishment of biological communities and have
      consequently altered the ecosystem.

PMID- 21881788
TI  - Diet and resource partitioning among anurans in irrigated rice fields in
      Pantanal, Brazil.
AB  - Artificial ponds or irrigated systems scattered throughout farmlands can offer
      important habitats for anurans and can be interesting sites for research on
      species resources use in a changing landscape. This study describes the diet and
      resource partitioning among anurans inhabiting irrigated rice fields in the
      Pantanal region. Twenty categories of prey were found in the stomachs of
      Leptodactylus chaquensis, L. elenae, L. podicipinus and Rhinella bergi, the most
      frequent being Coleoptera, Hymenoptera, larvae of Hexapoda, Hemiptera, Diptera
      and Orthoptera. The great differences found in the diet of these species in rice
      fields compared to other locations, according to available records in the
      literature, was the increased importance of Hemipitera and Orthoptera and the
      decrease in importance of Hymenoptera in the diet of leptodactylids. These
      differences might be attributed to changes in the availability of resources in
      response to habitat modification. Although diet composition was very similar
      among species, niche overlap was larger than expected by chance, suggesting that
      the competition for food resources is not, or has not been, a significant force
      in determining the structure of this frog community. Two non-exclusive hypotheses
      could be considered as a justification for this result: 1) the high niche overlap
      could result from resource availability, which is sufficient to satisfy all
      species without any strong competition; 2) or the high values of niche overlap
      could be a selective force driving species to compete, but there has not been
      enough time to express a significant divergence in the species diet because the
      study area is characterised as a dynamic habitat influenced by frequent and
      cyclical changes.

PMID- 21881789
TI  - Assessment and management of white mullet Mugil curema (Valencienne, 1836)
      (Mugilidae) fisheries of the south coast of Sao Paulo state, Brazil.
AB  - There is intense fishing activity, mainly artisanal, in the Cananeia, Iguape and
      Ilha Comprida Estuarine System. White mullet (Mugil curema) is one of the local
      fishery resources and is usually caught with gillnets and fish traps. This study
      aimed to characterise the Mugil curema fisheries thereby underpinning the
      management of the species in the region. The study was developed with data
      collected from landings in the town of Cananeia, Sao Paulo state, Brazil, from
      1995 to 2009. Production data, fishing effort and CPUE were used to assess the
      evolution of captures. The gillnets were characterised by interviewing fishermen
      from 16 communities in Cananeia. White mullet fishery has aroused the interest of
      fishermen in the region since the 80s and today it is one of the main products of
      artisanal estuarine fishery off the south coast of Sao Paulo. The major landings
      occur in the warmer months with fish traps and gillnets being the main fishing
      gear used. The largest catches occur in the spawning months of the species from
      October to April. The highest landings varied according to different fishing
      gear, showing differences primarily due to trade preferences and to the structure
      of the fishing gear. According to the index of abundance used in this study, the
      resource is overfished due to the progressive increase in fishing effort, so it
      is suggested that measures should be taken to control fishing effort, such as
      special fishing permits to catch white mullet, especially with gillnets. The
      current management measures neither meet the needs of fishermen nor the
      preservation of the resource, and must be reviewed in a participatory way with
      management agencies and the fishery sector, ensuring greater legitimacy and
      success in the sustainability of the activity.

PMID- 21881790
TI  - Anthropogenic sources and distribution of phosphorus in sediments from the
      Jaguaribe River estuary, NE, Brazil.
AB  - This paper estimates annual P emission to the Jaguaribe River estuary, NE Brazil,
      responsible for approximately 30% of the country's farmed shrimp production.
      Emissions increased three times between 2001 and 2006 and reached 43.9 t.year-1.
      These emissions make aquaculture the third main source of P for this estuary and
      are much smaller than emissions from agricultural sources and slightly lower than
      emissions from wastewater. Their relative contribution also increased from 10.5%
      to 20.5%. Temporal variability of P concentrations in estuarine bottom sediments
      also suggest an increase, but not as evident as the emissions. The spatial
      distribution and speciation of P (total P and inorganic P) in sampling stations
      located upstream and downstream from the main aquaculture area confirmed the
      importance of this source. Inorganic P was the dominant form present in sediments
      downstream and showed an increase from 67% to 75% of the total P present in the
      sediment.

PMID- 21881791
TI  - Reproductive cycle of Anomalocardia brasiliana (Mollusca: Bivalvia: Veneridae) in
      the estuary of the Cachoeira River, Ilheus, Bahia.
AB  - The aim of this study was to characterize the reproductive cycle of Anomalocardia
      brasiliana, typical of the estuarine region of the Cachoeira River, Ilheus,
      Bahia, Brazil. For this purpose, 20 specimens were collected biweekly between
      August 2005 and August 2006 on an intertidal bank (14o 48' 23" S and 39o 02' 47"
      W). The animals were measured on the anteroposterior axis (length), examined
      macroscopically and removed from the shell and fixed in Davidson's solution.
      Subsequently, the tissues were impregnated in paraffin, cut into 7 mm sections
      and stained with Harris hematoxylin and eosin (HE). The slides were examined
      under a light microscope. The water temperature at the site ranged from 24 to
      30.5 oC (mean: 27.4 oC; SD +/- 1.9), salinity from zero to 23 (mean: 13.7; SD +/-
      7.5) and rainfall from 28.3 mm to 248.8 mm monthly (yearly mean: 130 mm). The
      sample (n = 478) showed a sex ratio (M: F) of 1: 1.2 (p < 0.05) and no cases of
      hermaphroditism. There was no sexual dimorphism. Males and females showed
      reproductive synchrony. The reproductive cycle was continuous, with releases of
      gametes mainly in spring, summer and autumn. These results are similar to those
      found in other regions, but there was no reproductive rest period as reported for
      populations in higher latitudes.

PMID- 21881792
TI  - A novel antifungal protein from seeds of Sesbania virgata (Cav.) Pers.
      (Leguminosae-Faboideae).
AB  - A novel antifungal protein with a molecular mass around 50 kDa was purified from
      seeds of Sesbania virgata (Cav.) Pers. using ammonium sulfate fractionation
      followed by gel filtration on a Sephadex G-75 Superfine (Sigma) column and
      reverse-phase high performance liquid chromatography on a C8 column. The protein,
      designated FP1-A, with a novel N-terminal sequence AMVHSPGG(S)FS(P), showed
      growth inhibitory activity of filamentous fungi Aspergillus niger, Cladosporium
      cladosporioides, Colletotrichum gloeosporioides and Fusarium solani.

PMID- 21881793
TI  - Spermatic abnormalities of piracanjuba Brycon orbignyanus (Valenciennes, 1849)
      after cryopreservation.
AB  - The objective of this research was to verify the presence of spermatic
      abnormalities on semen of Brycon orbignyanus after cryopreservation. Semen was
      collected from ten four-year-old males who presented secondary reproductive
      characteristics for migrating fish. Sperm was evaluated for motility, vigor and
      spermatic morphology before and after cryopreservation. A cryoprotectant solution
      was made of 20 mL of yolk egg, 5.0 g of glucose and dimethyl sulfoxide diluted in
      distilled water (10 mL: 90 mL). The diluted semen (1:3, semen:solution) was
      submitted to nitrogen steam for 24 hours and then to liquid nitrogen (-196 oC)
      for 60 days. Cryopreservation decreased the percentage of normal spermatozoa from
      62.20% to 54.60%. Consequently, the percentage of spermatozoa with secondary
      abnormalities increased from 8.50% to 15.00%. However, there was no difference in
      primary abnormalities. Both spermatic motility and vigor were decreased in
      cryopreserved semen compared with fresh semen. In conclusion, cryopreservation of
      semen of B. orbignyanus increased the percentage of secondary abnormalities and
      decreased the spermatic motility and vigor.

PMID- 21881794
TI  - Histochemical analysis of seed reserve mobilization in Passiflora edulis Sims fo.
      flavicarpa O. Deg. (yellow passion fruit) during germination.
AB  - In the present work, we analyzed the histochemical aspects of Passiflora edulis
      seeds reserve mobilization during the first ten days of germination. Our results
      showed that mainly lipids present in the endosperm are used as a reserve source,
      and their levels reduce at the same time the radicle protrudes, between the
      fourth and sixth day of sowing. Furthermore, protein bodies are present in the
      cotyledons, which are degraded as germination occurs and are almost depleted by
      the time of radicle protrusion. Starch grains also appear in the late germination
      period, and it is not clear if there is any reserve wall polysaccharide
      consumption in the endosperm.

PMID- 21881795
TI  - Pollination of Byrsonima coccolobifolia: short-distance isolation and possible
      causes for low fruit production.
AB  - Byrsonima coccolobifolia is a tropical plant from the Malpighiaceae family,
      distributed in the neotropical savanna fields and pollinated by bees known as
      "collecting-oil bees". In this study, conducted in a Cerrado area located on a
      farm in the city of Silvania, GO, the following hypothesis was tested: the
      greater the isolation degree of a plant, the lower its fruit production due to
      access difficulties for pollinators. Using a linear regression analysis, it was
      possible to relate the fruiting rate with the degree of isolation of each B.
      coccolobifolia individual and consequently it was found that the isolation had no
      influence on the pollination rate, an unexpected event that can be explained by
      the distance amongst individuals not being large enough to limit the movement of
      pollinators, or because cross-pollination was not the predominant form of
      reproduction, since the rate of cross-pollination was similar to self
      pollination. It was also found that the proportion of fruits produced was lower
      than expected, a factor which may also have influenced the results.

PMID- 21881796
TI  - Seasonal influence on the hematological parameters in cultured Nile tilapia from
      southern Brazil.
AB  - This study evaluated seasonality in hematological parameters of Nile tilapia
      cultured in the state of Santa Catarina, southern Brazil. A total of 240 fish
      were examined during four seasons between April 2007 and March 2008 in three
      different fish farms. After being anesthetised in a benzocaine solution, blood
      samples were withdrawn into syringes containing a drop of 10% EDTA for
      hematological analysis. The results were compared between fish farms and seasons,
      which are well delimited in southern Brazil. In a traditional fish farm in
      Joinville in the summer, there was an increase in the percentage of hematocrit
      and in the red blood cell count. The highest values of total leukocytes were
      found in fish from fee-fishing in Blumenau in the autumn while the lowest values
      occurred in those from swine consorted system in Ituporanga in the summer.
      Thrombocytosis was observed in the autumn, and lymphocytosis was found in both
      the autumn and winter in tilapia from all fish farms investigated. Neutrophilia
      was only observed in winter and autumn in fish from Blumenau and Ituporanga. This
      work demonstrated the influence of seasonality and the handling characteristics
      of each fish farm on certain hematological parameters in Nile tilapia.

PMID- 21881797
TI  - Interaction between Apis mellifera L. and Baccharis dracunculifolia DC, that
      favours green propolis production in Minas Gerais.
AB  - In Minas Gerais, green propolis is produced from the collection of resinous
      substance found in shoot apices of Baccharis dracunculifolia. The aim of this
      study was to evaluate the biological parameters associated with the interaction
      Apis mellifera x Baccharis dracunculifolia, to elucidate the supply of resin for
      green propolis production in Minas Gerais. We selected male and female
      individuals of two populations of Baccharis dracunculifolia located on Sao Judas
      Tadeu Farm - FSJT, in the municipality of Betim, MG and the Experimental Garden
      of the Ezequiel Dias Foundation - HORTO, located in an urban area in Belo
      Horizonte, MG. We made weekly observations, from June 2007 to June 2008, and
      evaluated in both populations: richness and abundance of insect visitors; resin
      collecting visits of Apis mellifera; presence of Baccharopelma dracunculifoliae
      galls; growth of individuals and phenological phases. Statistical analyses were
      made using R software. The rainy season showed the highest number of visitors. A.
      mellifera collected resin in shoot apices of Baccharis dracunculifolia from
      August to April, only in the FSJT population, where galls of B. dracunculifoliae
      were also present. Ovoposition of gall inductor on host plants occurs during the
      rainy season, when there is a peak of visitants and resin collecting visits of
      honeybees. This fact stimulates plant defense strategies against parasitoids and
      predators, which includes the production of several secondary metabolites, and
      ultimately reduces competition for food by inhibiting the attack of other
      phytophagous insects, not adapted to the chemical environment of plant tissues.
      Green propolis production in Minas Gerais is related to the abundant supply of
      resin by Baccharis dracunculifolia, when they are parasitised by B.
      dracunculifoliae galls. They induce plant production of defense exudates, which
      attract Apis mellifera bees to collect resin and consequently favour the
      production of green propolis.

PMID- 21881798
TI  - First occurrence of Protapanteles (Protapanteles) enephes (Nixon, 1965)
      (Hymenoptera, Braconidae, Microgastrinae) in Brazil and new biological data.
AB  - Protapanteles (Protapanteles) enephes (Nixon, 1965) (Hymenoptera, Braconidae,
      Microgastrinae) was reared from the host Fountainea ryphea phidile (Geyer, 1837)
      (Lepidoptera, Nymphalidae, Charaxinae), collected on Croton floribundus Spreng.
      (Euphorbiaceae) in Sao Carlos, Sao Paulo state, Brazil. The hyperperparasitoids
      Conura sp. (Hymenoptera, Chalcididae) and a Pteromalidae species are registered
      on this microgastrine species. Male and female specimens and cocoon of
      Protapanteles (Protapanteles) enephes are illustrated for the first time.

PMID- 21881799
TI  - Desmodus rotundus (Mammalia: Chiroptera) on the southern coast of Rio de Janeiro
      state, Brazil.
AB  - Since the 1990s, attacks by hematophagous bats on humans and domestic animals
      have been reported both on the continent and on the islands on the southern coast
      of Rio de Janeiro state. The density of vampire bats was investigated based on
      percentage of captures during control of Desmodus rotundus samplings and during
      bat diversity research. In the present work, 203 individuals of D. rotundus were
      captured from 1993 to 2009, which corresponds to 11.88% of all bat captures
      carried out for species control in local villages and 1.58% of all captures in
      faunistic inventories. The density of D. rotundus is high even on the recently
      occupied islands where domestic animals have been introduced. It is probable that
      this species dispersed from the continent to the islands due to the introduction
      of domestic animals.

PMID- 21881800
TI  - Development of Loxosceles intermedia Mello-Leitao (1934) (Araneae, Sicariidae)
      genital tract.
AB  - We examined the post-embryonic development of the male and female genital
      apparatus of the brown spider, Loxosceles intermedia. The development of the
      genital apparatus for both sexes begins with the appearance of inner structures.
      In the male genital apparatus, formation of the testes occurs first, followed by
      differentiation of the duct, ampulla and vas deferens, and finally the formation
      of the genital opening and differentiation of the copulatory organ (secondary
      sexual characteristic). Similarly, the development of the female genital
      apparatus begins with the formation of the ovaries, followed by the appearance of
      oocytes in vitellogenesis, then the development of oviducts and uterus internus
      and, finally, the spermatheca. These data may be very important in further
      comparative studies on the development of the reproductive system of spiders.

PMID- 21881801
TI  - Age and growth of the Scalloped Hammerhead shark, Sphyrna lewini (Griffith and
      Smith, 1834), from the southern Brazilian coast.
AB  - Age and growth studies for the scalloped hammerhead shark, Sphyrna lewini
      (Griffith and Smith, 1834) caught along the southern Brazilian coast, were based
      on ring measurements of vertebrae sections of 115 males, 116 females and 14
      unknown sexed sharks between 48 and 344 cm total length (TL). The von Bertalanffy
      growth models were best fit using back-calculated data. The growth parameters
      obtained for males, were Linfinity = 266 cm; K = 0.05/year; L0 = 47 cm. For
      females, Linfinity = 300 cm; K = 0.05/year; L0 = 51 cm. An adult female reached
      217 cm TL and was 31.5 years old. On the other hand, an adult male was 29.5 years
      old and measured 234 cm TL. Longevity estimate for males and females was 55
      years. Therefore, S. lewini is a long-lived fish. Ageing precision, based on the
      IAPE index, was 5.6%. Marginal Increment analysis based on MIR index from
      hammerheads smaller than 105 cm, compared with the percentual of opaque and
      hyaline bands found per month ageing whole vertebrae, showed an annual ring
      formation, i.e., in winter.

PMID- 21881802
TI  - Biological aspects of Schizodon nasutus Kner, 1858 (Characiformes, Anostomidae)
      in the low Sorocaba river basin, Sao Paulo state, Brazil.
AB  - Four biological aspects of Schizodon nasutus in the low Sorocaba river basin, Sao
      Paulo, Brazil were analysed. These were accomplished during the year seasons. The
      fish diet and the feeding activity were investigated by studying the repletion
      index, which showed no significant differences between seasons. The food items
      analysed by frequency of occurrence and dominance showed a predominance of
      vegetable items in the diet. The reproduction, analysed by using the
      gonadosomatic index, indicated that the reproductive period occurs during the
      summer period when temperatures are higher and rainfalls are more intense. The
      amount of accumulated fat and condition factor varied according to reproduction,
      especially for females.

PMID- 21881803
TI  - Seasonal variation in metazoan parasites of Trichiurus lepturus (Perciformes:
      Trichiuridae) of Rio de Janeiro, Brazil.
AB  - This work aimed to study the temporal variation of metazoan parasites of
      Trichiurus lepturus from the coastal zone of Rio de Janeiro, Brazil. Between July
      2006 and June 2007, there were four seasonal quarterly samples of 30 specimens of
      T. lepturus. In addition to a group composed of anisakid larvae, we collected a
      total of 14 species of metazoan parasites: five digenean; five monogenean, two
      cestode larvae, one acanthocephalan larvae; and one copepod. With the exception
      of Lecithochirium microstomum and Lecithochirium sp., all species showed peaks of
      prevalence and abundance especially those fishes collected in summer, which may
      indicate a seasonal variation of these parasites in T. lepturus from the coast of
      Rio de Janeiro.

PMID- 21881804
TI  - Acetylcholinesterase inhibition by somes promising Brazilian medicinal plants.
AB  - A microplate assay and a thin-layer chromatography (TLC) "in situ" assay based on
      the Ellman assay was used to screen for acetylcholinesterase inhibitors from
      ethyl acetate and methanol extracts of Brazilian medicinal plants of families
      that, according to the literature, have traditional uses that might be connected
      with acetylcholinesterase inhibition. Eighteen species belonging to
      Convolvulaceae, Crassulaceae, Euphorbiaceae, Leguminosae, Malvaceae, Moraceae,
      Nyctaginaceae and Rutaceae families were tested. The most active plants were
      Ipomoea asarifolia (IC50 = 0.12 mg/mL), Jatropha curcas (IC50 = 0.25 mg/mL),
      Jatropha gossypiifolia (IC50 = 0.05 mg/mL), Kalanchoe brasiliensis (IC50 = 0.16
      mg/mL) and Senna alata (IC50 = 0.08 mg/mL). The most promising extracts were the
      Jatropha gossypiifolia and Senna alata species assuming there were compounds with
      a similar activity to galanthamine, which should contain about 1% of an active
      compound, or if present at lower levels even more active compounds than
      galanthamine (IC50 = 0.37 x 10-3 mg/mL) should be present.

PMID- 21881806
TI  - Occurrence of abnormalities on labral keel of Coronatella monacantha (Cladocera,
      Anomopoda, Chydoridae) in a population from Ceara, Brazil.

PMID- 21881805
TI  - Parasite diversity in Oxydoras niger (Osteichthyes: Doradidae) from the basin of
      Solimoes River, Amazonas state, Brazil, and the relationship between
      monogenoidean and condition factor.
AB  - This study describes the parasitic fauna of Oxydoras niger from the Coari Lake,
      tributary of the medium Solimoes River, State of Amazonas, Brazil, and the
      relationship between the number of Monogenoidea and the condition factor. From a
      total of 27 examined fish, 70.3% were parasitised by at least one parasite
      species as follows: Ichthyophthirius multifiliis (Protozoa), Chilodonella sp.
      (Protozoa), Cosmetocleithrum gussevi, C. confusus, C. parvum and Cosmetocleithrum
      sp. (Monogenoidea), Paracavisona impudica (Acanthocephala), Cucullanus
      grandistomis (Nematoda), Proteocephalus kuyukuyu (Cestoda) and Dadaytrema sp.
      (Digenea). Monogenoidea helminthes were the most prevalent parasite when compared
      to protozoan and intestinal helminthes. This study showed that O. niger has a
      great parasite diversity composed mainly of monogenoideans followed by
      acanthocephalan and digenean. This is the first record of Dadaytrema in O. niger
      from the Brazilian Amazon. There was a positive correlation between the number of
      monogenoideans and the condition factor (Kn) of fish, and with this mean
      intensity of infection, fish welfare was not affected.

PMID- 21881807
TI  - Moderate intensity physical training accelerates healing of full-thickness wounds
      in mice.
AB  - Physical training influences the cells and mediators involved in skin wound
      healing. The objective of this study was to determine the changes induced by
      different intensities of physical training in mouse skin wound healing. Ninety
      male C57BL6 mice (8 weeks old, 20-25 g) were randomized into three physical
      training groups: moderate (70% VO2max), high (80% VO2max), and strenuous
      intensity (90% VO2max). Animals trained on a motorized treadmill for 8 weeks (E
      lesion: physical training until the day of excisional lesion, N = 10) or 10 weeks
      (E euthan: physical training for 2 additional weeks after excisional lesion until
      euthanasia, N = 10), five times/week, for 45 min. Control groups (CG) trained on
      the treadmill three times/week only for 5 min (N = 10). In the 8th week, mice
      were anesthetized, submitted to a dorsal full-thickness excisional wound of 1
      cm2, and sacrificed 14 days after wounding. Wound areas were measured 4, 7, and
      14 days after wounding to evaluate contraction (d4, d7 and d14) and re
      epithelialization (d14). Fragments of lesion and adjacent skin were processed and
      submitted to routine histological staining. Immunohistochemistry against alpha
      smooth muscle actin (alpha-SMA) was performed. Moderate-intensity training (M)
      until lesion (M/E lesion) led to better wound closure 7 days after wounding
      compared to controls and M/E euthan (P < 0.05), and both moderate-intensity
      groups showed better re-epithelialization rates than controls (M/E lesion =
      85.9%, M/E euthan = 96.4% and M/CG = 79.9%; P < 0.05). Sections of M/E lesion and
      M/E euthan groups stained with hematoxylin-eosin, Picrosirius red and alpha-SMA
      showed the most mature granulation tissues among all trained groups and controls.
      Thus, moderate-intensity physical training improves skin wound healing.

PMID- 21881809
TI  - New multilocus sequence typing of MRSA in Sao Paulo, Brazil.
AB  - An increased incidence of nosocomial and community-acquired infections caused by
      methicillin-resistant Staphylococcus aureus (MRSA) has been observed worldwide.
      The molecular characterization of MRSA has played an important role in
      demonstrating the existence of internationally disseminated clones. The use of
      molecular biology methods in the surveillance programs has enabled the tracking
      of MRSA spread within and among hospitals. These data are useful to alert
      nosocomial infection control programs about the potential introduction of these
      epidemic clones in their areas. Four MRSA blood culture isolates from patients
      hospitalized at two hospitals in the city of Sao Paulo, Brazil, were analyzed;
      one of them was community acquired. The isolates were characterized as SCCmec,
      mecA and PVL by PCR, pulsed-field gel electrophoresis (PFGE) profile and
      molecular sequence typing (MLST) genotyping. The isolates presented type IV
      SCCmec, and none proved to be positive for PVL. The isolates showed a PFGE
      profile similar to the pediatric clone. MLST genotyping demonstrated that the
      isolates belonged to clonal complex 5 (CC5), showing a new yqiL allele gene,
      resulting in a new sequence typing (ST) (1176). Our results showed that strains
      of MRSA carrying a new ST are emerging in community and nosocomial infections,
      including bacteremia, in Sao Paulo, Brazil.

PMID- 21881808
TI  - A link between sleep loss, glucose metabolism and adipokines.
AB  - The present review evaluates the role of sleep and its alteration in triggering
      problems of glucose metabolism and the possible involvement of adipokines in this
      process. A reduction in the amount of time spent sleeping has become an endemic
      condition in modern society, and a search of the current literature has found
      important associations between sleep loss and alterations of nutritional and
      metabolic contexts. Studies suggest that sleep loss is associated with problems
      in glucose metabolism and a higher risk for the development of insulin resistance
      and type 2 diabetes mellitus. The mechanism involved may be associated with the
      decreased efficacy of regulation of the hypothalamus-pituitary-adrenal axis by
      negative feedback mechanisms in sleep-deprivation conditions. In addition,
      changes in the circadian pattern of growth hormone (GH) secretion might also
      contribute to the alterations in glucose regulation observed during sleep loss.
      On the other hand, sleep deprivation stress affects adipokines - increasing tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) and decreasing leptin
      and adiponectin -, thus establishing a possible association between sleep-debt,
      adipokines and glucose metabolism. Thus, a modified release of adipokines
      resulting from sleep deprivation could lead to a chronic sub-inflammatory state
      that could play a central role in the development of insulin resistance and type
      2 diabetes mellitus. Further studies are necessary to investigate the role of
      sleep loss in adipokine release and its relationship with glucose metabolism.

PMID- 21881810
TI  - Eccentric and concentric cardiac hypertrophy induced by exercise training:
      microRNAs and molecular determinants.
AB  - Among the molecular, biochemical and cellular processes that orchestrate the
      development of the different phenotypes of cardiac hypertrophy in response to
      physiological stimuli or pathological insults, the specific contribution of
      exercise training has recently become appreciated. Physiological cardiac
      hypertrophy involves complex cardiac remodeling that occurs as an adaptive
      response to static or dynamic chronic exercise, but the stimuli and molecular
      mechanisms underlying transduction of the hemodynamic overload into myocardial
      growth are poorly understood. This review summarizes the physiological stimuli
      that induce concentric and eccentric physiological hypertrophy, and discusses the
      molecular mechanisms, sarcomeric organization, and signaling pathway involved,
      also showing that the cardiac markers of pathological hypertrophy (atrial
      natriuretic factor, beta-myosin heavy chain and alpha-skeletal actin) are not
      increased. There is no fibrosis and no cardiac dysfunction in eccentric or
      concentric hypertrophy induced by exercise training. Therefore, the renin
      angiotensin system has been implicated as one of the regulatory mechanisms for
      the control of cardiac function and structure. Here, we show that the angiotensin
      II type 1 (AT1) receptor is locally activated in pathological and physiological
      cardiac hypertrophy, although with exercise training it can be stimulated
      independently of the involvement of angiotensin II. Recently, microRNAs (miRs)
      have been investigated as a possible therapeutic approach since they regulate the
      translation of the target mRNAs involved in cardiac hypertrophy; however, miRs in
      relation to physiological hypertrophy have not been extensively investigated. We
      summarize here profiling studies that have examined miRs in pathological and
      physiological cardiac hypertrophy. An understanding of physiological cardiac
      remodeling may provide a strategy to improve ventricular function in cardiac
      dysfunction.

PMID- 21881811
TI  - Diagnosis of adrenal failure in critically ill patients.
AB  - In the last two decades there was important evolution on the knowledge of the
      function of the hypothalamic-pituitary-adrenal axis. In the last decade, the
      expression "relative adrenal insufficiency" (RAI) was created, and more recently
      "critical illness-related corticosteroid insufficiency" (CIRCI) was used to
      designate those patients in which cortisol production was not sufficiently
      increased in stress situations. Patients with CIRCI have elevated hospital
      morbidity and mortality. Currently, there is a wide discussion about diagnostic
      criteria for this dysfunction. Besides basal cortisol, some publications now
      study the role of other tests, such as cortrosyn test - either in low (1 MUg) or
      high doses (250 MUg); free cortisol, salivary cortisol, metyrapone test and
      others. With this review, we aimed at summarizing the results of the most
      influent papers that intended to define diagnostic criteria for CIRCI. We also
      suggest an approach for CIRCI diagnosis and make it clear that the decision about
      steroid therapy in septic shock patients is matter apart from RAI.

PMID- 21881812
TI  - [Regulation of glucose and fatty acid metabolism in skeletal muscle during
      contraction].
AB  - The glucose-fatty acid cycle explains the preference for fatty acid during
      moderate and long duration physical exercise. In contrast, there is a high
      glucose availability and oxidation rate in response to intense physical exercise.
      The reactive oxygen species (ROS) production during physical exercise suggests
      that the redox balance is important to regulate of lipids/carbohydrate
      metabolism. ROS reduces the activity of the Krebs cycle, and increases the
      activity of mitochondrial uncoupling proteins. The opposite effects happen during
      moderate physical activity. Thus, some issues is highlighted in the present
      review: Why does skeletal muscle prefer lipids in the basal and during moderate
      physical activity? Why does glucose-fatty acid fail to carry out their effects
      during intense physical exercise? How skeletal muscles regulate the lipids and
      carbohydrate metabolism during the contraction-relaxation cycle?

PMID- 21881814
TI  - [Final height (FH) in Turner syndrome (TS): experience of 76 cases followed at
      the Pediatric Endocrinology Unit, Hospital de Clinicas, Federal University of
      Parana].
AB  - OBJECTIVE: To report the final height (FH) of 76 patients with Turner syndrome
      (TS). MATERIALS AND METHODS: Review of the files and calculation of z scores: of
      target height (TH), and FH according to NCHS/CDC/2000 and FH according to Lyon
      and cols. RESULTS: Patients were classified in three groups: A (n = 16),
      treatment with estrogens and progestogens; B (n = 21), treatment with oxandrolone
      (OX); C (n = 39), growth hormone (GH) plus OX. The z score of TH was not
      different among the groups and z score of FH was not different between A e B. Z
      score of FH of group C was greater than the other groups, > 2SDS of Lyon's curve
      and fitted on the 3(rd) percentile of NCHS/CDC. Multiple regression analysis
      showed type of treatment (p < 0.001) and maternal height (p = 0.02) as most
      influencing factors on FH. CONCLUSION: GH plus OX and maternal height contributed
      significantly to enhance FH of TS patients.

PMID- 21881813
TI  - Normocalcemic primary hyperparathyroidism in clinical practice: an indolent
      condition or a silent threat?
AB  - OBJECTIVE: To describe the characteristics of normocalcemic primary
      hyperparathyroidism (NPHPT) in patients seen for osteoporosis evaluation.
      PATIENTS AND METHODS: We examined the records of 156 women who came to the
      hospital to be screened for osteoporosis. Measurements of total calcium, PTH, 25
      hydroxy vitamin D, and beta-C-telopeptide were recorded. Bone mineral density and
      T-scores were evaluated by densitometry of the lumbar spine, femoral neck and
      distal one-third of the radius. The latter was only measured in patients with
      primary hyperparathyroidism. Nephrolithiasis and bone fractures were documented
      by a review of the medical records. RESULTS: We identified 14 patients with
      NPHPT, accounting for 8.9% of the population studied. In the medical records, the
      occurrence of kidney stones was reported in 28.6% of the patients with NPHPT, in
      contrast with only 0.7% of the noncarriers. Regarding the presence of general
      fractures, 21.4% of the patients with NPHPT were affected versus 16.2% of
      noncarriers. CONCLUSION: Data from our study suggest that NPHPT has a diverse
      phenotypic presentation, implying that this may not be an "indolent" disease.

PMID- 21881815
TI  - Frequency of thyroid carcinoma and thyroid autoimmunity in first-degree relatives
      of patients with papillary thyroid carcinoma: a single center experience.
AB  - OBJECTIVE: To evaluate the frequency of thyroid cancer and thyroid dysfunction in
      first-degree relatives of thyroid cancer patients, and to determine if there is a
      difference between familial and sporadic thyroid cancer. SUBJECTS AND METHODS:
      Fifteen first-degree relatives of seven families with at least two family members
      with thyroid cancer (TC) were compared with 128 first-degree relatives of 45
      families with only one family member affected. Laboratory and ultrasound
      evaluation, fine-needle aspiration biopsy and thyroid surgery were used as
      normally done in clinical practice. RESULTS: Thyroid dysfunction was similar
      between the two groups. The frequency of TC and autoimmunity in the group that
      had two relatives with known thyroid cancer was higher, compared with the
      families that had sporadic thyroid cancer among their family members (40% vs. 2%,
      p = 0.0001). CONCLUSION: Frequency of TC increases when more than one member of
      the family is affected. These findings suggest that these relatives should be
      screened more frequently than individuals in families in which only one case of
      TC is observed.

PMID- 21881816
TI  - [Impact of a minimum program of supervised exercises in the cardiometabolic risk
      in patients with morbid obesity].
AB  - OBJECTIVE: The objective aims at evaluating the impact of a minimum program of
      supervised physical exercise on functional capacity and cardiometabolic risk
      (CMR) in patients with morbid obesity. MATERIAL AND METHODS: By studying cases
      with pre and post analyses, we have assessed the variations in weight, functional
      capacity and in CMR, due to the program of supervised aerobic exercise on a
      weekly intensity of 30 minutes during a period of 6 months. RESULTS: We have
      studied 61 subjects, where 34 have only adhered to the intervention. There were
      significant changes in weight (-5.3 +/- 5.3 kg, p < 0.0001), distance in the 6
      minute walking test (69.8 +/- 48.6 m, p < 0.0001), systolic pressure (-23.8 +/-
      27.7 mmHg, p < 0.0001), diastolic pressure (-14.4 +/- 8.9 mmHg, p < 0.0001) and
      Framingham Score Risk (-4.4 +/- 5.1, p < 0.0001) in the adherent patients.
      CONCLUSION: The results show that a supervised exercise program of low intensity
      and frequency might interfere positively on CMR in individuals with morbid
      obesity.

PMID- 21881817
TI  - [Effect of triiodothyronine on the bone proteins expression during osteogenic
      differentiation of mesenchymal stem cells].
AB  - OBJECTIVE: The aim of this study was to evaluate the effect of T3 on the
      expression of osteocalcin, osteopontin and collagen I during osteogenic
      differentiation of mesenchymal stem cells (MSC). MATERIALS AND METHODS: The bone
      marrow cells of Wistar rats with 30 days of age were extracted, cultured and
      separated into five groups: control (undifferentiated), differentiated
      (osteogenic stimulus) and differentiated with T3 (10(-3) nM, 10(-2) nM and 100
      nM). For each group, four samples were cultured and were analyzed by real time RT
      PCR at 7, 14 and 21 days for quantification of gene transcripts for osteocalcin,
      osteopontin and collagen I. RESULTS: All the different groups without T3 or with
      T3 regardless of the concentration, showed the collagen I expression
      significantly lower expression, and osteocalcin and osteopontin expression
      significantly greater than that of undifferentiated MSC. Nevertheless, the group
      T3 100 nM showed higher expression of osteocalcin and a similar expression of the
      osteoblast culture. CONCLUSION: In conclusion, the triiodothyronine does not
      affect the expression of osteopontin and collagen I, but increases ostecalcin
      expression during osteogenic differentiation in vitro of the MSC, and this effect
      is dose-dependent.

PMID- 21881818
TI  - Conservative management of pituitary tumor apoplexy.
AB  - Pituitary tumor apoplexy is a rare neuroendocrine syndrome resulting, in most
      cases, from hemorrhage or infarctation of a pre-existing pituitary adenoma.
      Treatment recommendations vary; some authors advocate urgent surgical
      decompression of the tumor, whereas others suggest that conservative management
      can lead to recovery of neuro-ophthalmologic function. We describe two patients
      with pituitary tumor apoplexy who had clinically non-functioning macroadenomas
      and hypopituitarism, including hypogonadism. They were treated conservatively
      without surgery, and achieved tumor remission.

PMID- 21881819
TI  - First description of pseudohypoparathyroidism with frontal lobe calcification and
      normal serum calcium at the initial manifestation in an otherwise healthy seven
      year-old girl.
AB  - Pseudohypoparathyroidism (PHP) is characterized by resistance to the peripheral
      action of parathyroid hormone. We present a case of a seven-year-old girl who was
      admitted at the service of Instituto Materno Infantil de Pernambuco, IMIP, with
      motor episodes affecting the arms. Her calcium level was normal. Computed
      tomography showed calcifications in frontal lobes and basal ganglia. After six
      years: calcium was 5.5 mg/dL; phosphorus, 8.3 mg/dL and serum parathyroid hormone
      was 1,318 pg/mL. Pseudohypoparathyroidism diagnosis was considered. This is the
      first description of a case of pseudohypoparathyroidism without Albright's
      stigma, with cerebral calcification, and no calcium abnormalities at the initial
      clinical manifestation.

PMID- 21881820
TI  - Metabolic improvement by telmisartan beyond angiotensin receptor blockade: role
      of adipokines.

PMID- 21881821
TI  - Metabolic syndrome: did the creator kill the creature?

PMID- 21881822
TI  - Tcf-1 gene silence suppresses downstream gene expression in CD4(+) T cells from
      bone marrow of aplastic anemia patients.
AB  - CD4(+) T cells play a crucial role in the pathogenesis of acquired aplastic
      anemia (AA). Tcf-1 gene regulates T cell development and function, and it is
      significantly upregulated in the bone marrow CD4(+) T cells from patients with
      acquired AA. To explore the role of Tcf-1 in the pathogenesis of AA, we knocked
      down Tcf-1 gene in CD4(+) T cells of AA patients and studied the effects of Tcf-1
      silencing on its downstream gene expression. Upon transfection of psiRNA into
      marrow CD4(+) T cells from bone marrow of aplastic anemia patients, the
      expression of Tcf-1 was significantly knocked down; consequently, expressions of
      c-Myc and CD44 were also significantly reduced. Our results suggest that Tcf-1
      may contribute to pathogenesis of AA by regulating downstream gene expression
      such as c-myc and CD44.

PMID- 21881823
TI  - Quantification of plasma Epstein-Barr virus DNA for assessing treatment response
      in a patient with plasmablastic lymphoma.

PMID- 21881824
TI  - An imatinib-treated FIL1P1-PDGFRalpha chronic eosinophilic leukemia transforming
      to erythroid blast crisis: a case report.

PMID- 21881825
TI  - 3,4-Diarylmaleimides-a novel class of kinase inhibitors-effectively induce
      apoptosis in FLT3-ITD-dependent cells.
AB  - FLT3 kinase has become an attractive drug target in AML with up to 30% of cases
      harboring internal-tandem-duplication (ITD) mutations. For these, conferring a
      worse prognosis and decreased overall survival, several FLT3 tyrosine kinase
      inhibitors (TKIs) are currently being tested in clinical trials. However, when
      using these drugs as monotherapy, the problem of short duration of remissions and
      high incidence of TKI resistance has emerged. Here, we investigated two members
      of a novel class of tyrosine kinase inhibitors, 3,4-diarylmaleimides, for their
      efficacy on mutated FLT3 kinase. These compounds inhibit FLT3 kinase in an ATP
      competitive manner and effectively inhibit phosphorylation of downstream targets.
      3,4-Diarylmaleimides (DHF125 and 150) induce apoptosis in FLT3-ITD-dependent
      cells lines and patient blasts at low micromolar concentrations. They are
      retained in the cytoplasm of exposed cells for more than 24 h and synergize with
      chemotherapy and midostaurin. Both 3,4-diarylmaleimides show inhbition of FLT3
      ITD-related kinase autophosphorylation at distinct tyrosine residues when
      compared to midostaurin. In conclusion, this novel group of compounds shows
      differential inhibition patterns with regard to FLT3 kinase and displays a
      promising profile for further clinical development. Currently, experiments
      evaluating toxicity in murine models and unraveling the exact binding mechanism
      are under way to facilitate a potential clinical application.

PMID- 21881826
TI  - PSF suppresses tau exon 10 inclusion by interacting with a stem-loop structure
      downstream of exon 10.
AB  - Microtubule binding protein Tau has been implicated in a wide range of
      neurodegenerative disorders collectively classified as tauopathies. Exon 10 of
      the human tau gene, which codes for a microtubule binding repeat region, is
      alternatively spliced to form Tau protein isoforms containing either four or
      three microtubule binding repeats, Tau4R and Tau3R, respectively. The levels of
      different Tau splicing isoforms are fine-tuned by alternative splicing with the
      ratio of Tau4R/Tau3R maintained approximately at one in adult neurons. Mutations
      that disrupt tau exon 10 splicing regulation cause an imbalance of different tau
      splicing isoforms and have been associated with tauopathy. To search for factors
      interacting with tau pre-messenger RNA (pre-mRNA) and regulating tau exon 10
      alternative splicing, we performed a yeast RNA-protein interaction screen and
      identified polypyrimidine tract binding protein associated splicing factor (PSF)
      as a candidate tau exon 10 splicing regulator. UV crosslinking experiments show
      that PSF binds to the stem-loop structure at the 5' splice site downstream of tau
      exon 10. This PSF-interacting RNA element is distinct from known PSF binding
      sites previously identified in other genes. Overexpression of PSF promotes tau
      exon 10 exclusion, whereas down-regulation of the endogenous PSF facilitates exon
      10 inclusion. Immunostaining shows that PSF is expressed in the human brain
      regions affected by tauopathy. Our data reveal a new player in tau exon 10
      alternative splicing regulation and uncover a previously unknown mechanism of PSF
      in regulating tau pre-mRNA splicing.

PMID- 21881827
TI  - Interkinetic nuclear movement in the ventricular zone of the cortex.
AB  - The nuclei of neuroepithelial cells move along the apicobasal axis in
      synchronization with their cell cycle status. This motility is known as
      interkinetic nuclear movement. We discuss here the importance of cytoskeleton
      organization, the centrosome, molecular motors, cell polarity proteins, and their
      regulators in controlling and maintaining this typical behavior. Furthermore, due
      to the tight linkage between cell proliferation, cell cycle, and nuclear
      motility, we speculate that interkinetic nuclear movement is likely to be
      affected in the pathophysiology of microcephaly, where the brain size is markedly
      reduced.

PMID- 21881828
TI  - Circulating extracellular proteasome in the cerebrospinal fluid: a study on
      concentration and proteolytic activity.
AB  - Alterations of the intracellular ubiquitin-proteasome pathway are found in
      neurodegenerative and inflammatory disorders of the central nervous system, as
      well as in its malignancies. Inhibitory substrates of the proteasomes represent
      promising approaches to control autoimmune inflammations and induction of
      apoptosis in cancer cells. Extracellular circulating proteasomes are positively
      correlated to outcome prognosis in hematogenic neoplasias and the outcome in
      critically ill patients. Previously, we reported raised levels of proteolytic
      active 20S proteasomes in the extracellular alveolar space in patients with acute
      respiratory distress syndrome (ARDS). For the cerebrospinal fluid, we assumed
      that extracellular circulating proteasomes with enzymatic activity can be found,
      too. Cerebrospinal fluid (CSF) samples of twenty-six patients (14 females, 12
      males), who underwent diagnostic spinal myelography, were analyzed for leukocyte
      cell count, total protein content, lactate and interleukine-6 (Il-6)
      concentrations. CSF samples were analyzed for concentration and enzymatic
      activity of extracellular 20S proteasomes (fluorescenic substrate cleavage;
      femtokatal). Blood samples were analyzed with respect to concentration of
      extracellular circulating proteasomes. Choroidal plexus was harvested at
      autopsies and examined with immunoelectron microscopy (EM) for identification of
      possible transportation mechanisms. Statistical analysis was performed using SPSS
      (18.0.3). In all patients, extracellular proteasome was found in the CSF. The
      mean concentration was 24.6 ng/ml. Enzymatic activity of the 20S subunits of
      proteasomes was positively identified by the fluorescenic subtrate cleavage at a
      mean of 8.5 fkat/ml. Concentrations of extracellular proteasomes in the CSF,
      total protein content and Il-6 were uncorrelated. Immunoelectron microscopy
      revealed merging vesicles of proteasomes with the outer cell membrane suggestive
      of an exozytic transport mechanism. For the first time, extracellular circulating
      20S proteasome in the CSF of healthy individuals is identified and its enzymatic
      activity detected. A possible exozytic vesicle-bond transportation mechanism is
      suggested by immunoelectron microscopy. The present study raises more questions
      on the function of extracellular proteasome in the CSF and encourages further
      studies on the role of extracellular protesomes in pathological conditions of the
      central nervous system (tumor lesions and inflammatory processes).

PMID- 21881829
TI  - PEMT G523A (V175M) is associated with sporadic Alzheimer's disease in a Chinese
      population.
AB  - There is evidence that increased concentrations of circulating homocysteine are
      associated with Alzheimer's disease (AD). Phosphatidylethanolamine N
      methyltransferase (PEMT) is an important catalyst involved in the production of
      homocysteine. We investigated the association of a functional single nucleotide
      polymorphism (rs7946) in PEMT with sporadic AD risk in a Han Chinese population
      that included 386 AD patients and 366 controls. PEMT G523A was genotyped by
      either sequencing or PCR-restriction fragment length polymorphism analysis. The
      plasma homocysteine concentrations of 210 subjects were determined by high
      performance liquid chromatography. Significant higher frequency of the A allele
      was detected in AD cases than in controls (A vs. G, p = 0.007, OR = 1.482, 95% CI
      1.114-1.972). After adjusting for gender, age/age at onset, and APOE epsilon4
      status, logistic analysis showed rs7946 was associated with AD in a dominant
      model (AA + GA vs. GG, p = 0.007, OR = 1.596, 95% CI 1.138-2.240). When
      stratified by APOE epsilon4 status or gender, the significant difference was only
      observed in the APOE epsilon4 non-carriers and in the female subjects,
      respectively. We did not find a relationship of this polymorphism with plasma
      homocysteine levels. These results suggested that PEMT G523A is associated with
      AD and that the A allele is an APOE epsilon4-independent risk factor for AD among
      Han Chinese women.

PMID- 21881830
TI  - Prognostic value of free DNA quantification in serum and cerebrospinal fluid in
      glioma patients.
AB  - Unlike uniformly truncated DNA released from apoptotic nondiseased cells, free
      DNA released from dead tumor cells varies in size. Free DNA has been considered
      as a candidate biomarker for malignant tumors. We obtained serum samples from 70
      patients with glioma and 22 healthy volunteers as control and cerebrospinal fluid
      (CSF) samples from 20 patients with glioma and eight nonneoplastic controls with
      hydrocephalus or arachnoid cyst and performed preoperative analysis of free DNA
      concentration and integrity by a quantitative polymerase chain reaction. With two
      primers sets amplifying short and long free DNA fragments (ALU115 and ALU247),
      free DNA integrity was determined by ratio of the concentration of ALU247 over
      ALU115 (ALU247/115). Our results indicate that free DNA integrity and the ratio
      of long fragments to short fragments may be a useful diagnostic assay for glioma.
      In summary, the CSF-free DNA concentration and integrity may serve as a new
      marker for the diagnosis of glioma.

PMID- 21881831
TI  - Behavioral variant frontotemporal dementia with corticobasal degeneration
      pathology: phenotypic comparison to bvFTD with Pick's disease.
AB  - Patients with corticobasal degeneration (CBD) pathology present with diverse
      clinical syndromes also associated with other neuropathologies, including
      corticobasal syndrome, progressive nonfluent aphasia, and an Alzheimer's-type
      dementia. Some present with behavioral variant frontotemporal dementia (bvFTD),
      though this subtype still requires more detailed clinical characterization. All
      patients with CBD pathology and clinical assessment were reviewed (N = 17) and
      selected if they initially met criteria for bvFTD [bvFTD(CBD), N = 5]. Available
      bvFTD patients with Pick's [bvFTD(Pick's), N = 5] were selected as controls.
      Patients were also compared to healthy older controls [N = 53] on
      neuropsychological and neuroimaging measures. At initial presentation, bvFTD(CBD)
      showed few neuropsychological or motor differences from bvFTD(Pick's).
      Neuropsychiatrically, they were predominantly apathetic with less florid social
      disinhibition and eating disturbances, and were more anxious than bvFTD(Pick's)
      patients. Voxel-based morphometry revealed similar patterns of predominantly
      frontal atrophy between bvFTD groups, though overall degree of atrophy was less
      severe in bvFTD(CBD), who also showed comparative preservation of the
      frontoinsular rim, with dorsal > ventral frontal atrophy, and sparing of temporal
      and parietal structures relative to bvFTD(Pick's) patients. Despite a remarkable
      overlap between the two patient types, bvFTD patients with underlying CBD
      pathology show subtle clinical features that may distinguish them from patients
      with Pick's disease neuropathology.

PMID- 21881832
TI  - Exploring the role of soluble factors associated with immune regulatory
      properties of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSCs) are characterized as multipotent stromal cells with
      the capacity for both self-renewal and differentiation into mesodermal cell
      lineages. MSCs also have a fibroblast-like phenotype and can be isolated from
      several tissues. In recent years, researchers have found that MSCs secrete
      several soluble factors that exert immunosuppressive effects by modulating both
      innate (macrophages, dendritic and NK cells) and adaptive (B cells and CD4+ and
      CD8+ T cells) immune responses. This review summarizes the principal trophic
      factors that are related to immune regulation and secreted by MSCs under both
      autoimmune and inflammatory conditions. The understanding of mechanisms that
      regulate immunity in MSCs field is important for their future use as a novel
      cellular-based immunotherapy with clinical applications in several diseases.

PMID- 21881834
TI  - Sunitinib and Thrombosis.

PMID- 21881833
TI  - Stable changes in mesenchymal stromal cells from multiple myeloma patients
      revealed through their responses to Toll-like receptor ligands and epidermal
      growth factor.
AB  - In human multiple myeloma (MM), the tumor cells exhibit strict dependence on bone
      marrow (BM) stromal elements. It has been suggested that, in turn, MM cells
      modify multipotent stromal cells (MSCs), diverting them to support the myeloma.
      We investigated MM-derived MSCs by comparing their toll-like receptor (TLR)
      responses to those of MSCs derived from healthy controls. We now report that MM
      derived MSCs manifested intact proliferation responses and IL-6 secretion and
      their adipose and osteogenic differentiation responses to TLR ligands were also
      similar to those of healthy controls, ranging from augmentation to inhibition.
      However, MM-derived MSCs were found to be defective in IL-8 secretion and ERK1/2
      phosphorylation following TLR-2 activation. Moreover, MM-derived MSCs failed to
      respond to EGF by elevation of ERK1/2 phosphorylation. The persistence of these
      changes in extensively cultured MM-derived MSCs, suggests that these cells are
      stably, if not irreversibly modified.

PMID- 21881835
TI  - A case of bilateral Chikungunya neuroretinitis.

PMID- 21881836
TI  - Bariatric surgery: impact on body composition after Roux-en-Y gastric bypass.
AB  - BACKGROUND: The aim of this study was to analyze the impact of bariatric surgery
      on the body composition of patients suffering from class III obesity at different
      postoperative time intervals. METHODS: The body composition of 114 patients
      undergoing Roux-en-Y gastric bypass surgery was measured prior to surgery (T0)
      and then 30 (T30) and 180 (T180) days following surgery. Body composition was
      evaluated using the following parameters: total body mass, body mass index,
      excess weight, percentage of excess weight loss, relative body fat (%F), lean
      body mass (LBM), and fat tissue mass (FTM). To determine these variables,
      validated formulas and equations proper to obese men and women were employed.
      RESULTS: A significant reduction in %F (41.5%), LBM (20.3%), FTM (37.9%) was
      noted at each time interval (p <= 0.01). CONCLUSIONS: Bariatric surgery proved to
      be effective in reducing total body mass and body fat at every time interval.
      However, dietary measures emphasizing adequate protein intake may be implemented
      in order to reduce loss of LBM and, coupled with frequent physical activity, may
      help curtail the impact the surgery has on morphological variables.

PMID- 21881837
TI  - Brain tissue echogenicity--implications for substantia nigra studies in
      parkinsonian patients.
AB  - The aim of the present study was to assess the origin of the substantia nigra
      hyperechogenicity in Parkinson disease patients. The cause of hyperechogenicity
      was tested on an animal model. Fresh porcine brains were injected consecutively
      with ferritin, apoferritin and water. Then, glioma samples were inserted into
      animal model. The echogenicity of the region of interest was assessed before and
      after experimental procedures. We observed the same echogenicity of porcine brain
      before and after injections of iron-loaded ferritin, apoferritin and water.
      Increased echogenicity of glioma samples compared to surrounding porcine brain
      tissue could be clearly seen. We postulate that the relative gliosis might be, at
      least partially, responsible for the increased echogenicity of the substantia
      nigra in Parkinson disease patients. Keeping in mind all limitations and
      inaccuracies of animal model used, it seems that hyperechogenicity of substantia
      nigra is caused rather by structural changes within the brain tissue than by
      increased iron concentration.

PMID- 21881838
TI  - Continuous drug delivery in early- and late-stage Parkinson's disease as a
      strategy for avoiding dyskinesia induction and expression.
AB  - The treatment of the motor symptoms of Parkinson's disease (PD) is dependent on
      the use of dopamine replacement therapy in the form of L: -dopa and dopamine
      agonist drugs. However, the development of dyskinesia (chorea, dystonia,
      athetosis) can become treatment limiting. The initiation of dyskinesia involves a
      priming process dependent on the presence of nigral dopaminergic cell loss
      leading to alterations in basal ganglia function that underlie the expression of
      involuntary movements following the administration of each drug dose. Once
      established, dyskinesia is difficult to control and it is even more difficult to
      reverse the priming process. Dyskinesia is more commonly induced by L: -dopa than
      by dopamine agonist drugs. This has been associated with the short duration of L:
      -dopa causing pulsatile stimulation of postsynaptic dopamine receptors compared
      to the longer acting dopamine agonists that cause more continuous stimulation. As
      a result, the concept of continuous dopaminergic stimulation (CDS) has arisen and
      has come to dominate the strategy for treatment of early PD. However, CDS has
      flaws that have led to the general acceptance that continuous drug delivery (CDD)
      is key to the successful treatment of PD. Studies in both experimental models of
      PD and in clinical trials have shown CDD to improve efficacy, but reduce
      dyskinesia induction, and to reverse established involuntary movements. Two key
      clinical strategies currently address the concept of CDD: (1) in early-, mid- and
      late-stage PD, transdermal administration of rotigotine provides 24 h of drug
      delivery; (2) in late-stage PD, the constant intraduodenal administration of L: 
      dopa is utilized to improve control of motor symptoms and to diminish established
      dyskinesia. This review examines the rationale for CDD and explores the clinical
      benefit of using such a strategy for the treatment of patients with PD.

PMID- 21881840
TI  - Expression of matrix metalloproteinase-1, -9, -13, and tissue inhibitor of
      metalloproteinases-1 in basal cell carcinomas of the eyelid.
AB  - BACKGROUND: Matrix metalloproteinases (MMPs) and tissue inhibitors of
      metalloproteinases (TIMPs) function in the remodelling of the extracellular
      matrix in morphogenesis, angiogenesis, tissue repair, and tumor invasion.
      Elevated levels of distinct MMPs in tumor tissue are related to worse prognosis.
      However, no overall consistent pattern of expression in human cancer has been
      identified. The aim of the present study was to evaluate the expression of MMP-1,
      -9, -13 and TIMP-1 in tumor epithelial cells and surrounding connective tissue in
      primary basal cell carcinomas (BCC) of the eyelid, and to assess their role as
      prognostic markers for tumor recurrence. METHODS: Surgical specimens of 49
      histologically proven primary BBCs of the eyelid of different histological
      subtypes were included. Immunohistological studies were performed using
      antibodies against MMP-1, MMP-9, MMP-13 and TIMP-1, and staining intensity was
      analyzed semi-quantitatively. RESULTS: MMP-1, -9, -13, and TIMP-1 were expressed
      at various intensities in epithelial tumor cells and surrounding stromal cells
      including fibroblasts, inflammatory cells, and vascular endothelial cells in all
      tumor subtypes. Staining was especially prominent at the invading edge of the
      BCC. A statistically significant correlation was seen between increased TIMP-1
      expression in tumor and/or stromal cells with the presence of MMP-13 (p = 0.007
      and p < 0.0001 respectively). Moreover, TIMP-1 expression in tumor and/or stroma
      was significantly associated with relapse (p = 0.012 and p = 0.042 respectively).
      CONCLUSION: MMP-9, MMP-13 and TIMP-1 expression may serve as a prognostic marker
      for early tumor invasiveness. Moreover, up-regulation of TIMP-1 in tumor and/or
      surrounding stromal cells may indicate an increased risk for BCC recurrence.

PMID- 21881841
TI  - Comparison of measurement error of Cirrus HD-OCT and Heidelberg Retina Tomograph
      3 in patients with early glaucomatous visual field defect.
AB  - BACKGROUND: To compare the measurement error of Cirrus HD-OCT and Heidelberg
      Retina Tomograph 3 (HRT3) in patients with early glaucomatous visual field
      defect. METHODS: Thirty-nine consecutive patients (39 eyes) with early
      glaucomatous visual field defect were included. One eye of a patient was examined
      with Cirrus HD-OCT and HRT3 in one session. Each instrument was used by two
      operators, each taking two measurements in turn. We performed measurements of
      average retinal nerve fiber layer (RNFL) thickness and RNFL thickness in four
      quadrants with Cirrus HD-OCT and 13 stereometric parameters of the optic nerve
      head and RNFL with HRT3. RESULTS: Cirrus HD-OCT parameters performed much better
      than HRT3 stereometric parameters. Mean (for both operators) intraoperator within
      subject coefficient of variation of the best Cirrus HD-OCT parameter (average
      RNFL thickness) was 2.6-2.7 times lower than the best HRT3 parameters [mean cup
      depth and rim area (P < 0.001)]. Mean intraoperator variability of RNFL thickness
      in quadrants (except nasal quadrant) was also significantly lower with OCT than
      with HRT. The interoperator within-subject coefficients of variation for both
      average RNFL thickness and RNFL thickness in all quadrants were significantly
      lower than the interoperator variability of best HRT3 parameter [mean cup depth
      (P < 0.001)]. The within-subject coefficient of variation of the average/mean
      RNFL thickness assessed by both instruments was 5.4-7.3 times lower for Cirrus HD
      OCT. Among HRT3 parameters, mean cup depth, rim area and linear cup/disk ratio
      were the least variable, while cup volume, cup area and cup/disc area ratio were
      the most variable parameters. CONCLUSIONS: Cirrus HD-OCT provides excellent
      intrasession intra- and interoperator repeatability of the RNFL measurements,
      especially of the average RNFL thickness in primary open-angle glaucoma (POAG)
      patients and POAG suspects with early glaucomatous visual field defect. The
      measurement error (expressed as within-subject coefficient of variation) of RNFL
      measurements by Cirrus HD-OCT is much lower than the error of HRT3 measurements
      of stereometric parameters of the optic nerve head and RNFL.

PMID- 21881842
TI  - Homozygosity for the +674C>T polymorphism on VEGF gene is associated with age
      related macular degeneration in a Brazilian cohort.
AB  - PURPOSE: To investigate the association between VEGF gene polymorphism and age
      related macular degeneration (AMD) in a Brazilian cohort. METHODS: We examined
      160 affected individuals and 140 sex- and age-matched controls recruited at the
      Vision Institute and the Retina Department, Sao Geraldo Hospital, Minas Gerais
      Federal University, Brazil, between 2007 and 2011. Genotyping for the VEGF
      rs1413711 single nucleotide polymorphism (SNP) (+674C>T) was performed. The
      incidence rate ratios and 95% confidence interval (CI) for AMD for this genotype
      was calculated. The odds ratio (OR) was also assessed by using logistic
      regression, controlling for CFH and LOC387715 risk genotype. RESULTS: We observed
      a prevalence of homozygosity (TT genotype) of 18.1% for rs1413711 among AMD cases
      compared with 5.8% among controls (P < 0.002). The ORs for this polymorphism were
      3.6 (95%CI 1.6-8.2) for homozygous subjects and 1.5 (95%CI 1.1-2.1, P < 0.01) if
      the subject had at least one risk allele. When we studied separately exudative
      and dry AMD groups, this polymorphism was statistically significant for both
      groups. Controlling for CFH and LOC387715 risk genotype the OR was 3.0 for VEGF
      homozygous, and the OR increases if the patient is homozygous for the three
      genes. CONCLUSION: The present data suggests that VEGF TT genotype is associated
      with AMD among Brazilian patients.

PMID- 21881843
TI  - Cryopreservation and long-term culture of transformed murine corneal endothelial
      cells.
AB  - PURPOSE: To characterize the morphology and gene expression of transformed murine
      corneal endothelial cells. METHODS: Primary immortomouse corneal endothelial
      cells were continuously cultured before and after cryopreservation. Morphologic
      assessment, real time-reverse transcriptase polymerase chain reaction ((RT)-PCR)
      and immunofluorescence studies were performed using newly cultured cells, cells
      that had been continuously in culture for 1 year, and cryopreserved cells, to
      assess for structural and functional integrity. The expression of corneal
      endothelial markers zonula occludens-1 (ZO1), NaK-ATPase and collagen VIII
      (alpha2) (COL8A2), and myofibroblast markers Desmin, alpha smooth muscle actin
      (alphaSMA), and Vimentin was assessed and compared by both RT-PCR and
      immunofluorescence. RESULTS: Cells in culture formed a monolayer, and exhibited a
      polygonal shape after reaching confluence. Cells retained this morphology during
      the full observation time of 12 months and when reused after cryopreservation.
      Immunofluorescence experiments exhibited positive staining for NaK-ATPase and
      COL8A2 with low variability between the three groups. In RT-PCR experiments, ZO1,
      COL8A2 and Desmin were increased in fresh and thawed cells, alphaSMA was
      decreased, and NaK-ATPase and Vimentin remained unchanged, compared to 12-month
      old cells. Comparing fresh and thawed cells, COL8A2 was increased in thawed
      cells, while Desmin was increased in fresh cells. CONCLUSIONS: Using the
      immortomouse strain, murine corneal endothelial cells can be propagated over a
      long time period and be used after cryopreservation. Cells retain the expression
      of NaK-ATPase, but show some decline in ZO1 and COL8A2 over time and after
      cryopreservation. The expression of myofibroblast markers suggests an endothelial
      to-mesenchymal transformation process in culture.

PMID- 21881844
TI  - Luminance-modulated adaptation in the global flash mfERG: a preliminary study of
      early retinal functional changes in high-risk glaucoma patients.
AB  - PURPOSE: To investigate the association of the luminance-modulation global flash
      multifocal electroretinogram (mfERG) and other clinical assessments of vision in
      subsets of subjects at high risk of developing glaucomatous damage. METHODS:
      Eighteen subjects (28 eyes) with asymmetric glaucoma and ocular hypertension were
      measured in this longitudinal study of visual field, OCT, and multifocal
      electroretinogram (mfERG). Five ophthalmic examinations were scheduled, once
      every 12 months over a 4-year period. The mfERG was assessed using a luminance
      modulated global flash stimulation paradigm. The adaptive index which we have
      reported previously was calculated. RESULTS: There was a significant thinning of
      the peripapillary retinal nerve fiber layer over the course of the study for eyes
      with ocular hypertension, or for fellow eyes with asymmetric glaucoma which
      initially had an abnormal adaptive index; such eyes showed a thinning rate of 
      3.59 and -3.69 MUm/year, respectively. However, no significant thinning was found
      for eyes which initially had a normal adaptive index. Two subjects were shown to
      have glaucomatous damage, confirmed by abnormal thinning of the retinal nerve
      fiber layer and visual field loss respectively at the last visit. However, these
      patients had shown an abnormal adaptive index in the mfERG measurement at the
      first visit. CONCLUSIONS: The adaptive index calculated from the measurement of
      luminance-modulated global flash mfERG is useful for predicting progression of
      signs related to glaucoma, especially in high-risk groups. The abnormal adaptive
      index reflects the change in fast-adaptive mechanisms in the retina and indicates
      the risk of developing glaucoma.

PMID- 21881845
TI  - GDF-15: a novel serum marker for metastases in uveal melanoma patients.
AB  - BACKGROUND: About 50% of patients with uveal melanoma (UM) develop metastases
      during the course of their disease. We analyzed serum levels of Growth
      Differentiation Factor-15 (GDF-15), with the aim of identifying patients with
      early metastases. METHODS: GDF-15 concentration was measured using an enzyme
      linked immunosorbent assay (ELISA) in serum samples from 188 UM patients (170
      patients without metastases; 18 patients with clinically detectable metastases)
      and 18 healthy control individuals. Data were analyzed with respect to
      differences between patients with and without clinically detectable UM
      metastases. GDF-15 serum levels were further analyzed with regard to significant
      patient and tumor characteristics as revealed by histology and multiplex ligation
      dependent probe amplification (MLPA) to determine chromosome 3 copy number. GDF
      15 expression in UM was investigated by immunohistochemistry. RESULTS: Patients
      with clinically detectable metastases had significantly higher GDF-15 serum
      levels compared to those without clinically detectable metastases as well as to
      healthy individuals (ANOVA; p < 0.001). GDF-15 concentrations in UM patients with
      overt clinically detectable metastases were significantly higher than those in UM
      patients with a second malignancy in remission but without clinically detected UM
      metastases (ANOVA; p < 0.001). No association between serum concentration of GDF
      15 and clinical, pathological, and genetic features was observed. GDF-15 protein
      was only expressed in a minority of UM cells in most tumors. CONCLUSIONS: Our
      data suggest that GDF-15 can be used as a serum marker for the diagnosis of
      metastases in UM patients. Further data collection and analysis are necessary to
      evaluate a possible prognostic role of GDF-15 in predicting early metastases.

PMID- 21881846
TI  - A new locus in chromosome 2q37-qter is associated with posterior polar cataract.
AB  - PURPOSE: To study the genetic basis of autosomal dominant posterior polar
      cataracts in two Chinese pedigrees. MATERIALS AND METHODS: Peripheral blood
      samples were collected and genomic DNA was isolated. A genome-wide scan, using
      microsatellite markers at approximately 10-cm intervals and additional
      microsatellite markers for the positive region, was performed. Haplotype data
      were processed using Cyrillic software (version 2.1) to define the region of the
      disease gene. Mutation analysis was carried out for candidate genes. Sequencing
      data were analyzed with the software Sequence Scanner v1.0. RESULTS: A maximum
      two-point LOD score (Z (max)) of 2.53 and 2.03 was obtained at marker D2S125 with
      recombination theta = 0.00 in the two families. The possible disease genes were
      located at approximately 8.44-cM between the marker D2S125 and the terminal of
      chromosome 2q, namely, 2q37-qter. Candidate genes, such as Gamma-crystallins
      (CRYGA-D), septin 2 (SEPT2), aquaporin 12B (AQP12B), and chemokine orphan
      receptor 7 (CXCR7), were sequenced but no causative mutations were found.
      CONCLUSIONS: Our results suggest that an unidentified gene in chromosome 2q37
      qter is associated with posterior polar cataract, which may have an implication
      in understanding the genetic and molecular mechanisms of cataracts.

PMID- 21881847
TI  - A potential therapeutic strategy for inhibition of ocular neovascularization with
      a new endogenous protein: rhEDI-8t.
AB  - BACKGROUND: Endogenous angiogenesis inhibitors act as natural negative feedback
      in the focal area during the neovascularization process, and have less
      interference on physiological angiogenesis, and thus fewer negative side-effects.
      These inhibitors are potential candidates to combine with or substitutes for
      current popular anti-angiogenesis treatments to have synergistic effect. In this
      study, the effects of recombinant endothelial growth inhibitor protein (rhEDI
      8t), a novel endogenous protein originated from collagen VIII, was investigated
      on ocular neovascularization (NV). Endostatin, a well-identified endogenous
      angiogenesis inhibitor, was compared in parallel and served as a positive
      control. METHODS: The inhibitory effect of rhEDI-8t on vascular endothelial cells
      was evaluated by a human umbilical vascular endothelial cells (HUVEC)
      proliferation test and a bovine aortic endothelial cells (BAEC) migration
      experiment. The effect of rhEDI-8t on ocular NV was further investigated in mice
      with choroidal neovascularization (choroidal NV) induced by laser, ischemic
      retinopathy and transgenic mice with expression of VEGF in photoreceptors
      (rho/VEGF) respectively. RESULTS: RhEDI-8t inhibited the growth of HUVECs and
      migration of BAECs stimulated by basic fibroblast growth factor (bFGF). Mice
      intravitreally treated with rhEDI-8t showed a significant reduction of choroidal
      NV, retinal NV and subretinal NV. CONCLUSION: Endogenous angiogenesis inhibitor
      rhEDI-8t showed a potent anti-angiogenesis effect in both in vitro and in vivo
      experiments. It contributed to the suppression of ocular NV. The study suggested
      that rhEDI-8t could be a subsidiary potent therapeutic medicine in addition to
      anti-VEGF therapy in future clinical anti-angiogenesis treatment.

PMID- 21881849
TI  - Reduction of cerebral infarct size by dronedarone.
AB  - PURPOSE: In the ATHENA trial, dronedarone reduced the incidence of stroke in
      patients with atrial fibrillation. Since smaller cerebral infarcts are sometimes
      asymptomatic, the reduced incidence of stroke might reflect reduction of infarct
      size (IS) by dronedarone. However, no data on this effect of dronedarone are
      available. METHODS: In 60 rats, the middle cerebral artery was occluded (MCAO)
      for 1 h followed by reperfusion. IS was assessed at day 7. Animals were examined
      using a neurological 5 points score. Twelve animals served as controls (group A),
      12 animals received 30 mg/kg (group B) and 100 mg/kg (group C) dronedarone daily
      starting 3 days before MCAO; 12 animals received 30 mg/kg (group D) starting 2 h
      after MCAO. In all groups treatment was maintained until day 7. In 12 additional
      animals (6 controls, 6 pretreated animals) fractional anisotropy (FA) was
      assessed using magnetic resonance imaging (MRI). RESULTS: IS in group A was 151
      +/- 45 mm(3) versus 94 +/- 42 mm(3) in group B, 79 +/- 29 mm(3) in group C, and
      127 +/- 51 mm(3) in group D, respectively (B,C,D P < 0.05 vs. A). Neuroscores and
      weight loss (expressed as percent of initial weight) were less in treatment
      groups: 1.8 +/- 0.6 and 91% in group B, 1.4 +/- 0.5 and 93% in group C, and 2.1
      +/- 0.6 and 89% in group D compared to 2.4 +/- 0.5 and 83% in controls (B,C,D P <
      0.05 vs. A). FA in the ischemic penumbra was significantly higher in treated than
      in control animals (0.44 +/- 0.2 vs. 0.35 +/- 0.17; P < 0.05). CONCLUSIONS:
      Dronedarone administered before and after MCAO reduces IS and improves FA and
      neurological outcome in transient cerebral ischemia.

PMID- 21881848
TI  - Hemodynamic responses to visual stimulation in children with sickle cell anemia.
AB  - Blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF)-based
      functional magnetic resonance imaging (fMRI) were used to measure primary visual
      cortex responses to photic stimulation in 23 children (12.4  +/-  0.7 years old)
      with sickle cell anemia (SCA) and 21 clinical controls (11  +/-  1.0 years old).
      The objectives were to investigate the effect of SCA on detection of brain
      activation with fMRI and to explore the relationship between fMRI responses and
      global cognitive function. The BOLD responses were diminished in children with
      SCA. Clinical indicators of disease severity were greatest in patients without
      detectable visual cortex activation, but blood hemoglobin concentration and
      resting CBF were not predictive of BOLD signal amplitude in the SCA patients.
      Unexpectedly, the BOLD signal amplitude was positively associated (r(s)  >=  0.8,
      p  <=  0.05) with Wechsler Abbreviated Scale of Intelligence scores, suggesting
      that fMRI may help clarify medical, hemodynamic, and neural factors that mediate
      adverse effects of SCA on neurocognitive function.

PMID- 21881839
TI  - Mechanisms underlying the onset and expression of levodopa-induced dyskinesia and
      their pharmacological manipulation.
AB  - A significant proportion of patients with Parkinson's disease (PD) receiving
      dopamine replacement therapy in the form of levodopa develop dyskinesia that
      becomes a major complicating factor in treatment. Dyskinesia can only be
      effectively treated by a reduction in drug dose, which limits efficacy, by co
      administration of the weak NMDA antagonist amantadine or by surgical treatment
      (pallidotomy, DBS). This raises the important question of why dyskinesia occurs
      in PD and how it can be avoided or suppressed by pharmacological treatment. This
      review assesses some of the mechanisms that underlie dyskinesia induction and
      expression from presynaptic changes in dopaminergic neurones to postsynaptic
      alterations in basal ganglia function and examines potential approaches to
      prevention and treatment. These include glutamatergic approaches where agents
      that directly or indirectly alter glutamatergic neurotransmission modify the
      intracellular influx of Ca(2+) and reduce the formation of nitric oxide by
      neuronal nitric oxide synthase that may form an integral component of the complex
      cascade of events leading to dyskinesia. There is increasing evidence for the
      role of serotoninergic neurones in dyskinesia induction related to non
      physiological formation and release of dopamine and serotoninergic agonists can
      modify dyskinesia expression. Similarly, noradrenergic receptors may serve to
      alter dyskinesia intensity and alpha-2-adrenoceptor antagonists alter the
      expression of levodopa-induced dyskinesia in both experimental models of PD and
      in man. Finally, other potential approaches to dyskinesia treatment based on
      manipulation of opiate, cannabinoid, adenosine and histamine receptors are
      considered. The conclusion is that the cause of levodopa-induced dyskinesia
      remains to be fully elucidated and that new approaches to treatment through non
      dopaminergic mechanisms are required to control the onset and expression of
      involuntary movements.

PMID- 21881850
TI  - LOX-1 and obesity.
AB  - Obesity is one of the most common lifestyle-related diseases. Being closely
      associated with insulin resistance, hypertension and dyslipidemia, it is also a
      component of metabolic syndrome and is involved in the development of
      atherosclerosis and cardiovascular and renal ailments. Obesity is also
      accompanied with a state of chronic inflammation. Lectin-like oxidized low
      density lipoprotein receptor-1 (LOX-1), a receptor for oxidized low density
      lipoprotein (ox-LDL), is expressed not only in endothelial cells, but also in
      macrophages, vascular smooth muscle cells, platelets and adipocytes. LOX-1 binds
      multiple ligands, has diverse physiological functions and plays a critical role
      in the signal transduction. It may well turn out to be a key, or very important,
      factor in the development of hypertension, diabetes mellitus and hyperlipidemia,
      the most important risk factors for atherosclerosis. In recent studies, LOX-1
      upregulation appears to be a vital factor in obesity and its complications. This
      review summarizes current knowledge of obesity and the relationship between LOX-1
      and obesity.

PMID- 21881851
TI  - Do atherosclerosis and obesity-associated susceptibility to cancer share
      causative link to oxLDL and LOX-1?

PMID- 21881852
TI  - Shorter telomeres in patients with cerebral autosomal dominant arteriopathy and
      leukoencephalopathy (CADASIL).
AB  - CADASIL is a hereditary systemic vasculopathy which affects mainly small cerebral
      arteries and is caused by mutations in the Notch3 gene. Misfolding of Notch3 is
      linked to endoplasmic reticulum stress and increased reactive oxygen species,
      which may result in dysfunction of endothelial cells, inflammation and ischemia.
      Oxidative stress and inflammation may induce a rapid telomere shortening in
      peripheral blood leukocytes (PBLs). The aim of this study was to assess the
      telomere length in PBLs from 29 patients with a genetic diagnosis of CADASIL by
      using a modified quantitative real-time polymerase chain reaction based assay.
      PBL telomere length was significantly shorter in CADASIL patients (T/S ratio =
      0.17, 95% CI, 0.14-0.20) than in the controls (T/S ratio = 0.31, 95% CI, 0.27
      0.35, t-test p < 0.001). Moreover, patients with functional dependence displayed
      shorter telomeres than those with functional independence (p = 0.039). Our data
      provide the first evidence that PBL telomere length is shortened in CADASIL
      disease, and this may be a systemic oxidative stress indicator in CADASIL
      patients, providing a possible biomarker of disease progression and for future
      therapeutic strategies.

PMID- 21881853
TI  - Si-doped graphene: an ideal sensor for NO- or NO2-detection and metal-free
      catalyst for N2O-reduction.
AB  - Exploring and evaluating the potential applications of two-dimensional graphene
      is an increasingly hot topic in graphene research. In this paper, by studying the
      adsorption of NO, N(2)O, and NO(2) on pristine and silicon (Si)-doped graphene
      with density functional theory methods, we evaluated the possibility of using Si
      doped graphene as a candidate to detect or reduce harmful nitrogen oxides. The
      results indicate that, while adsorption of the three molecules on pristine
      graphene is very weak, Si-doping enhances the interaction of these molecules with
      graphene sheet in various ways: (1) two NO molecules can be adsorbed on Si-doped
      graphene in a paired arrangement, while up to four NO(2) molecules attach to the
      doped graphene with an average adsorption energy of -0.329 eV; (2) the N(2)O
      molecule can be reduced easily to the N(2) molecule, leaving an O-atom on the Si
      doped graphene. Moreover, we find that adsorption of NO and NO(2) leads to large
      changes in the electronic properties of Si-doped graphene. On the basis of these
      results, Si-doped graphene can be expected to be a good sensor for NO and NO(2)
      detection, as well as a metal-free catalyst for N(2)O reduction.

PMID- 21881854
TI  - Management of patients with atherosclerotic carotid occlusion.
AB  - OPINION STATEMENT: * Patients with acute ischemic stroke due to atherosclerotic
      carotid artery occlusion (ACAO) should receive intravenous tissue plasminogen
      activator (alteplase) if they meet eligibility criteria of the National Institute
      of Neurological Disorders and Stroke (NINDS) or the European Cooperative Acute
      Stroke Study III (ECASS III).  * Patients with acute stroke due to ACAO who are
      not eligible for intravenous tissue plasminogen activator should receive aspirin.
      Heparin or heparin-like drugs do not improve outcome and should not be used.  *
      Therapy for prevention of recurrent stroke in patients with ACAO should consist
      of lifestyle modifications, risk factor intervention, and antiplatelet drugs.
      Warfarin is not indicated.  * Extracranial-intracranial bypass surgery provides
      no benefit over medical therapy in preventing recurrent stroke in a general
      population of patients with ACAO or in any subgroups selected by clinical,
      arteriographic, or hemodynamic criteria.  * Other surgical or endovascular
      procedures have no proven value in treating or preventing stroke due to ACAO.  *
      Asymptomatic carotid occlusion has a benign prognosis and requires no specific
      treatment other than lifestyle modification and risk factor intervention.

PMID- 21881855
TI  - A longitudinal examination of serious adolescent offenders' perceptions of
      chances for success and engagement in behaviors accomplishing goals.
AB  - We examined antisocial adolescents' perceptions of the importance of and their
      ability to accomplish positive life outcomes (e.g., employment) and avoid
      negative ones (e.g., arrests) during their transition from adolescence to young
      adulthood. Participants were 1,354 adolescents from the Pathways to Desistance
      project, a multisite longitudinal study of seriously antisocial adolescents.
      Participants' perceptions of the importance and likelihood of accomplishing
      positive adult goals at one age uniquely predicted how often they engaged in
      behaviors that were consistent with these goals the following year. Our findings
      suggest that among serious adolescent offenders aspirations to achieve positive
      goals are related to engaging in behaviors that bring adolescents' current selves
      more in line with their aspired-to future selves. We discuss the implications of
      these findings for prevention and intervention efforts.

PMID- 21881856
TI  - Predictors and outcomes associated with trajectories of revenge goals from fourth
      grade through seventh grade.
AB  - The present study identified longitudinal trajectories of revenge goals in a
      sample of at-risk youth (N = 240; 63.3% male) followed from fourth grade through
      seventh grade. Three revenge goal trajectory groups were identified: a low-stable
      group, an increasing group, and a decreasing group. The increasing and decreasing
      groups were initially more behaviorally and affectively dysregulated and believed
      that aggression would gain them more rewards relative to the low-stable group.
      The increasing group was also more fearfully reactive compared to the decreasing
      group. Revenge goal trajectory groups also predicted trajectories of reactive and
      proactive aggression from 4th through 7th grade. The increasing group was more
      reactively aggressive and depressed and had poorer social skills in 8th grade
      compared to the other groups. Together, results highlight the importance of
      considering revenge motivations as an indicator of risk and a potential focus for
      intervention.

PMID- 21881857
TI  - Rat intermedin1-47 does not improve functional recovery in postischemic hearts.
AB  - Intermedin, a novel member of the calcitonin/calcitonin gene-related peptide
      family identified from vertebrate genomes, may directly affect cardiac function
      but current studies revealed no clear picture. The aims of our study were to
      compare direct contractile effects of intermedin on cardiomyocytes to that on the
      whole organ and to investigate whether intermedin improves postischemic recovery
      independent of an effect on acute reperfusion injury. Isolated adult rat
      ventricular cardiomyocytes were electrically paced and cell shortening was
      monitored as a readout associated to cardiac performance. Calcium transients were
      analyzed by Fura-2AM loading of these cells. Isolated rat hearts were
      investigated by Langendorff perfusion under nonischemic conditions and after 45
      min no-flow ischemia followed up by 30-min reperfusion prior to drug testing.
      Intermedin caused a positive contractile effect on cardiomyocytes that was
      mediated by protein kinase A activation and accompanied by improved calcium
      transients. In contrast, intermedin reduced left ventricular developed pressure
      in Langendorff-perfused rat hearts. This negative inotropic effect was attenuated
      by inhibition of nitric oxide synthesis. In postischemic hearts (impaired nitric
      oxide synthesis), the negative inotropic effect was attenuated but no positive
      inotropic effect occurred. However, intermedin caused robust vasodilation in
      nonischemic and postischemic hearts. Our findings suggest that the peptide binds
      preferentially to vascular cells in the intact organ. The loss of nitric oxide
      induction in postischemic hearts attenuates a negative inotropic effect of
      intermedin but does not improve cardiac performance independent of acute
      reperfusion injury.

PMID- 21881858
TI  - Morphine alters M. bovis infected microglia's ability to activate gammadelta T
      lymphocytes.
AB  - Microglia, the macrophages of the central nervous system (CNS), are both the
      principle target cells for Mycobacterium infection in the CNS and serve a
      critical role in defense of the brain. If microglia's functions are altered due
      to immunosuppressive agents such as opiates, perturbation in defense of the brain
      may occur, including defense against CNS Tuberculosis. This study was designed to
      determine if Mycobacterium infected microglia activate gammadeltaT lymphocytes
      and if the opiate morphine alters the capability of microglia to activate
      gammadeltaT lymphocytes. gammadeltaT lymphocytes proliferated, produced IFN
      gamma, and demonstrated cytolytic response upon exposure to Mycobacterium bovis
      infected microglia. IFN-gamma, and antigen specific cytotoxicity were both
      markedly impaired due to morphine treatment.

PMID- 21881859
TI  - Effect of mycophenolate sodium in scleroderma-related interstitial lung disease.
AB  - This study aims to determine the effectiveness of mycophenolate sodium (MS) in
      patients with scleroderma (SSc)-related interstitial lung disease (ILD). In a
      prospective observational study, we evaluated 14 consecutive SSc-ILD patients who
      were treated with MS for 12 months. The effect of MS on lung function was
      examined by using longitudinal data analytic methods. Wilcoxon rank-sum tests
      were used to examine the forced vital capacity (FVC), forced expiratory volume in
      1 s (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO) by
      pulmonary function testing. As a group, the median values for FVC, FEV1 and DLCO
      did not change significantly after 12 months of MS therapy and fulfilled the
      definition of stable disease by the American Thoracic Society. Individually,
      after 12 months of treatment, 6 out of 14 patients showed a pulmonary improvement
      defined as an increase of more than 10% in FVC, and 5 out of 14 patients remained
      stable. By contrast, the median FVC had declined a non-significant 7.2% from the
      previous 12 months before MS initiation. No significant drug adverse effects were
      registered. These prospective data suggest that MS is a safe and well-tolerated
      therapy for SSc-ILD patients, and it is capable of preventing functional
      pulmonary deterioration.

PMID- 21881860
TI  - Perfluorinated compounds in a coastal industrial area of Tianjin, China.
AB  - Perfluorinated compounds (PFC) in water, sediment, soil, and biota from the
      coastal industrial area of Tianjin, China, were measured to provide baseline
      information and to determine possible sources and potential risk to wildlife.
      Perfluorooctanesulfonate (PFOS) was the predominant PFC with maximum
      concentrations of 10 ng/L in water, and 4.3, 9.4, and 240 ng/g dw in sediment,
      soil, and fish, respectively. Perfluorooctanoate (PFOA) concentration in water
      ranged from 3.0 to 12 ng/L. Perfluoroundecanoate (PFUnA) and Perfluorododecanoate
      (PFDoA) were detected in solid matrices, respectively, at concentrations of <LOQ
      to 1.2 ng/g dw and 0.27-0.81 ng/g dw in sediments, and <LOQ to 1.0 ng/g dw and
      0.26-0.61 ng/g dw in soils. Concentrations of PFOS, PFUnA, and PFDoA in sediment
      and soil from this industrialized and urbanized area were greater than those
      previously reported, while PFOS and PFOA in water and biota were both less than
      reported threshold concentrations for adverse effects in wildlife.

PMID- 21881862
TI  - Retraction note: Groundwater contaminations and health perspectives in developing
      world case study: Gaza Strip.

PMID- 21881861
TI  - Residues of fluoroquinolones in marine aquaculture environment of the Pearl River
      Delta, South China.
AB  - Concentrations and distributions of selected fluoroquinolones (norfloxacin,
      ciprofloxacin and enrofloxacin) in water, sediments and nine kinds of fish
      species collected from 6 sites in two marine aquaculture regions of the Pearl
      River Delta, China, were analyzed by using high-performance liquid chromatography
      with fluorescence detector (HPLC). The results showed that the concentrations of
      ciprofloxacin and enrofloxacin were below the limits of quantification (LOQ) in
      all water samples except for norfloxacin. Norfloxacin and ciprofloxacin
      concentrations ranged from 1.88 to 11.20 ng g(-1) dry wt, 0.76-2.42 ng g(-1) dry
      wt in sediments collected from the Dapeng'ao region (sites 1-3) and ranged from
      2.31 to 4.75 ng g(-1) dry wt, 1.26-1.76 ng g(-1) dry wt in sediments collected
      from the Hailing Island region (sites 4-6), respectively. However, no
      enrofloxacin was found in all sediment samples. The three fluoroquinolones (FQs)
      were detected in all fish samples, and the concentrations were higher in liver
      tissues than those in muscle tissues. The levels of norfloxacin were higher than
      ciprofloxacin and enrofloxacin in both liver and muscle tissues. Among the nine
      marine fish species, Siganus fuscescens from Hailing Island had a significantly
      high level of norfloxacin in liver tissue (254.58 ng g(-1) wet wt), followed by
      Sparus macrocephalus (133.15 ng g(-1) wet wt) from Dapeng'ao, and the lowest
      value was Lutianus argentimaculatus (5.18 ng g(-1) wet wt) from Hailing Island.
      The obtained results of FQs in present study do not represent a risk to the human
      health in Guangdong coastal area, based on the maximum residue limits (MRLs)
      established by Chinese Government and the acceptable daily intake (ADI)
      recommended by the Food and Agriculture Organization and World Health
      Organization (FAO/WHO).

PMID- 21881864
TI  - Osteolysis following resorbable poly-L-lactide-co-D, L-lactide PLIF cage use: a
      review of cases.
AB  - STUDY DESIGN: Report of case series. OBJECTIVE: To report a problem with
      bioabsorbable poly-L-lactide-co-D, L-lactide, PLDLLA, posterior lumbar
      instrumented fusion (PLIF) cage implants. SUMMARY OF BACKGROUND DATA: Synthetic
      bioabsorbable implants have recently been introduced to spinal surgery and their
      indications and applications are still being explored. There is evidence that the
      use of bioabsorbable cages may be of benefit in interbody spinal fusion. METHODS:
      We present a case series of nine patients who have undergone PLIF with
      bioabsorbable cages in the lumbar spine. RESULTS: At follow-up over at least 1
      year, four of these patients were found to have osteolysis around the implant on
      CT scanning. One of these patients underwent an operation to remove the cage and
      histology sent during surgery suggested that the implant had caused the bone loss
      and there was no evidence of infection. Another patient had ongoing pain in
      relation to the lysis, while the other two patients with lysis remained
      asymptomatic. CONCLUSIONS: PLDLLA cage, which has high osteolytic nature, is
      considered not suitable as a fusion cage.

PMID- 21881865
TI  - Reliability and validity of the cross-culturally adapted French version of the
      Core Outcome Measures Index (COMI) in patients with low back pain.
AB  - PURPOSE: To conduct a cross-cultural adaptation of the Core Outcome Measures
      Index (COMI) into French according to established guidelines. METHODS: Seventy
      outpatients with chronic low back pain were recruited from six spine centres in
      Switzerland and France. They completed the newly translated COMI, and the Roland
      Morris disability (RMQ), Dallas Pain (DPQ), adjectival pain rating scale, WHO
      Quality of Life, and EuroQoL-5D questionnaires. After ~14 days RMQ and COMI were
      completed again to assess reproducibility; a transition question (7-point Likert
      scale; "very much worse" through "no change" to "very much better") indicated any
      change in status since the first questionnaire. RESULTS: COMI whole scores
      displayed no floor effects and just 1.5% ceiling effects. The scores for the
      individual COMI items correlated with their corresponding full-length reference
      questionnaire with varying strengths of correlation (0.33-0.84, P < 0.05). COMI
      whole scores showed a very good correlation with the "multidimensional" DPQ
      global score (Rho = 0.71). 55 patients (79%) returned a second questionnaire with
      no/minimal change in their back status. The reproducibility of individual COMI 5
      point items was good, with test-retest differences within one grade ranging from
      89% for 'social/work disability' to 98% for 'symptom-specific well-being'. The
      intraclass correlation coefficient for the COMI whole score was 0.85 (95% CI 0.76
      0.91). CONCLUSIONS: In conclusion, the French version of this short,
      multidimensional questionnaire showed good psychometric properties, comparable to
      those reported for German and Spanish versions. The French COMI represents a
      valuable tool for future multicentre clinical studies and surgical registries
      (e.g. SSE Spine Tango) in French-speaking countries.

PMID- 21881866
TI  - Three-dimensional movements of the lumbar spine facet joints and segmental
      movements: in vivo examinations of normal subjects with a new non-invasive
      method.
AB  - INTRODUCTION: Examination with CT and image registration is a new technique that
      we have previously used to assess 3D segmental motions in the lumbar spine in a
      phantom. Current multi-slice computed tomography (CT) offers highly accurate
      spatial volume resolution without significant distortion and modern CT scanners
      makes it possible to reduce the radiation dose to the patients. Our aim was to
      assess segmental movement in the lumbar spine with the aforementioned method in
      healthy subjects and also to determine rotation accuracy on phantom vertebrae.
      MATERIAL AND METHOD: The subjects were examined in flexion-extension using low
      dose CT. Eleven healthy, asymptomatic subjects participated in the current study.
      The subjects were placed on a custom made jig which could provoke the lumbar
      spine into flexion or extension. CT examination in flexion and extension was
      performed. The image analysis was performed using a 3D volume fusion tool,
      registering one of the vertebrae, and then measuring Euler angles and distances
      in the registered volumes. RESULTS: The mean 3D facet joint translation at L4-L5
      was in the right facet joint 6.1 mm (3.1-8.3), left facet joint 6.9 mm (4.9-9.9),
      at L5-S1: right facet joint 4.5 mm (1.4-6.9), and for the left facet joint 4.8 mm
      (2.0-7.7). In subjects the mean angles at the L4-L5 level were: in the sagittal
      plane 14.3 degrees , coronal plane 0.9 degrees  (-0.6 to 2.8), and in the
      transverse plane 0.6 degrees  (-0.4 to 1.5), in the L5-S1 level the rotation was
      in sagittal plane 10.2 degrees  (2.4-16.1), coronal plane 0 degrees  (-1.2 to
      1.2), and in the transverse plane 0.2 degrees  (-0.7 to 0.3). Repeated analysis
      for 3D facet joint movement was on average 5 mm with a standard error of mean of
      0.6 mm and repeatability of 1.8 mm (CI 95%). For segmental rotation in the
      sagittal plane the mean rotation was 11.5 degrees  and standard error of mean 1
      degrees . The repeatability for rotation was 2.8 degrees  (CI 95%). The accuracy
      for rotation in the phantom was in the sagittal plane 0.7 degrees , coronal plane
      1 degrees , and 0.7 in the transverse plane. CONCLUSION: This method to assess
      movement in the lumbar spine is a truly 3D method with a high precision giving
      both visual and numerical output. We believe that this method for measuring spine
      movement is useful both in research and in clinical settings.

PMID- 21881867
TI  - Expert's comment concerning grand rounds case entitled "a traumatic, high-energy
      and unstable fracture of the C5 vertebra managed with kyphoplasty: a previously
      unreported case" (by Nasir A. Quraishi and Sherief Elsayed).
AB  - Case presentation of a cervical spine fracture treated by kyphoplasty. The review
      of the case, especially the careful re-assessment of the x-rays reveals that the
      treatment goals have not been achieved (motion preservation, functional
      restoration of the vertebral body). The case report is an excellent example of
      our biased viewpoint in assessing our efforts.

PMID- 21881868
TI  - Natural killer (NK) cells: an important role in the immune system's defense
      against viral infections. Introduction.

PMID- 21881869
TI  - Four-year results following treatment of intrabony periodontal defects with an
      enamel matrix derivative alone or combined with a biphasic calcium phosphate.
AB  - The aim of this study was to evaluate the 4-year clinical outcomes following
      regenerative surgery in intrabony defects with either EMD + BCP or EMD. Twenty
      four patients with advanced chronic periodontitis, displaying one-, two-, or
      three-walled intrabony defect with a probing depth of at least 6 mm, were
      randomly treated with either EMD + BCP (test) or EMD alone (control). The
      following clinical parameters were evaluated at baseline, at 1 year and at 4
      years after regenerative surgery: plaque index, gingival index, bleeding on
      probing, probing depth, gingival recession, and clinical attachment level (CAL).
      The primary outcome variable was CAL. No differences in any of the investigated
      parameters were observed at baseline between the two groups. The test group
      demonstrated a mean CAL change from from 10.8 +/- 1.6 mm to 7.4 +/- 1.6 mm (p <
      0.001) and to 7.6 +/- 1.7 mm (p < 0.001) at 1 and 4 years, respectively. In the
      control group, mean CAL changed from 10.4 +/- 1.3 at baseline to 6.9 +/- 1.0 mm
      (p < 0.001) at 1 year and 7.2 +/- 1.2 mm (p < 0.001) at 4 years. At 4 years, two
      defects in the test group and three defects in the control group have lost 1 mm
      of the CAL gained at 1 year. Compared to baseline, at 4 years, a CAL gain of >=3
      mm was measured in 67% of the defects (i.e., in 8 out of 12) in the test group
      and in 75% of the defects (i.e., in 9 out of 12) in the control group. There were
      no statistically significant differences in any of the investigated parameters at
      1 and at 4 years between the two groups. Within their limits, the present results
      indicate that: (a) the clinical improvements obtained with both treatments can be
      maintained over a period of 4 years, and (b) in two- and three-walled intrabony
      defects, the addition of BCP did not additionally improve the outcomes obtained
      with EMD alone. In two- and three-walled intrabony defects, the combination of
      EMD + BCP did not show any advantage over the use of EMD alone.

PMID- 21881870
TI  - Aberrant expression of beta-catenin and its association with DeltaNp63, Notch-1,
      and clinicopathological factors in oral squamous cell carcinoma.
AB  - The present study focuses on the correlation between the expression pattern of
      beta-catenin (component of Wnt signaling), DeltaNp63 (proliferation marker), and
      Notch 1 (transmembrane receptor) in oral squamous cell carcinoma. The study also
      aims to investigate the interaction between beta-catenin and DeltaNp63 in oral
      cancer. Furthermore, we also analyzed the prognostic significance of beta
      catenin, DeltaNp63, and Notch 1 in oral squamous cell carcinoma.
      Immunohistochemical analysis of beta-catenin, DeltaNp63, and Notch 1 were done in
      62 cases of oral squamous cell carcinoma. Co-immunoprecipitation analysis was
      done to study the possible interaction between beta-catenin and DeltaNp63 in oral
      cancer. Kaplan-Meier method was used to estimate overall and disease-free
      survival, and the Log-rank test was used to compare the resulting curves.
      Statistically significant positive correlation was found between the localization
      of beta-catenin and the expression of DeltaNp63 (p = 0.001**, r (s) = 0.427),
      whereas, no significant association was found between the expression pattern of
      beta-catenin and Notch 1. Interestingly, interaction between beta-catenin and
      DeltaNp63 was observed in oral carcinoma. Moreover, beta-catenin and DeltaNp63
      may be related to worst survival in oral carcinoma. Statistically significant
      positive association between localization of beta-catenin and expression of
      DeltaNp63 suggests that they might have dependent roles in maintaining the
      proliferation of oral carcinoma cells. In addition, the downregulated expression
      of Notch 1 was related to invasion and differentiation status of oral carcinoma
      cells. Furthermore, beta-catenin and DeltaNp63 may be used as independent
      prognostic markers of oral carcinoma. On the other hand, interaction of beta
      catenin with DeltaNp63 may be a key event in maintaining the proliferation of
      oral carcinoma cells. The present study indicates that beta-catenin and DeltaNp63
      may be used as independent prognostic markers of oral carcinoma and the
      interaction of beta-catenin with DeltaNp63 may be a crucial event in regulating
      proliferation and differentiation of oral carcinoma cells, which may be used as a
      target for therapeutic implications.

PMID- 21881871
TI  - Ratiometric high-resolution imaging of JC-1 fluorescence reveals the subcellular
      heterogeneity of astrocytic mitochondria.
AB  - Using the mitochondrial potential (DeltaPsi(m)) marker JC-1 (5,5',6,6'
      tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide) and high
      resolution imaging, we functionally analyzed mitochondria in cultured rat
      hippocampal astrocytes. Ratiometric detection of JC-1 fluorescence identified
      mitochondria with high and low DeltaPsi(m). Mitochondrial density was highest in
      the perinuclear region, whereas DeltaPsi(m) tended to be higher in peripheral
      mitochondria. Spontaneous DeltaPsi(m) fluctuations, representing episodes of
      increased energization, appeared in individual mitochondria or synchronized in
      mitochondrial clusters. They continued upon withdrawal of extracellular Ca(2+),
      but were antagonized by dantrolene or 2-aminoethoxydiphenylborate (2-APB). Fluo-3
      imaging revealed local cytosolic Ca(2+) transients with similar kinetics that
      also were depressed by dantrolene and 2-APB. Massive cellular Ca(2+) load or
      metabolic impairment abolished DeltaPsi(m) fluctuations, occasionally evoking
      heterogeneous mitochondrial depolarizations. The detected diversity and
      DeltaPsi(m) heterogeneity of mitochondria confirms that even in less structurally
      polarized cells, such as astrocytes, specialized mitochondrial subpopulations
      coexist. We conclude that DeltaPsi(m) fluctuations are an indication of
      mitochondrial viability and are triggered by local Ca(2+) release from the
      endoplasmic reticulum. This spatially confined organelle crosstalk contributes to
      the functional heterogeneity of mitochondria and may serve to adapt the
      metabolism of glial cells to the activity and metabolic demand of complex
      neuronal networks. The established ratiometric JC-1 imaging-especially combined
      with two-photon microscopy-enables quantitative functional analyses of individual
      mitochondria as well as the comparison of mitochondrial heterogeneity in
      different preparations and/or treatment conditions.

PMID- 21881872
TI  - Attention, impulsivity, and cognitive flexibility in adult male rats exposed to
      ethanol binge during adolescence as measured in the five-choice serial reaction
      time task: the effects of task and ethanol challenges.
AB  - RATIONALE: Alcohol abuse is prevalent in adolescent humans, but the long-term
      behavioral consequences of binge alcohol drinking are unknown. OBJECTIVES: This
      study investigated the long-term effects of adolescent intermittent ethanol (AIE)
      exposure on attention and impulsivity. METHODS: Adolescent male rats were exposed
      to 5 g/kg of 25% (v/w) ethanol every 8 h for 4 days. During adulthood, rats were
      tested in the five-choice serial reaction time task (5-CSRTT) assessing
      attention, impulsivity and cognitive flexibility. RESULTS: There was no metabolic
      tolerance to ethanol in adolescent rats during AIE exposure. In the 5-CSRTT under
      baseline conditions, there were no differences between AIE-exposed and control
      rats in accuracy, omissions, or premature responses, although AIE-exposed rats
      tended to make more timeout responses than control rats. The short-duration
      stimulus challenge decreased accuracy and increased omissions and timeout
      responses in both AIE-exposed and control rats. The long intertrial interval
      challenge increased premature responses in all rats. An ethanol challenge
      decreased correct responses, and increased omissions in control, but not in AIE
      exposed, rats. Control, but not AIE-exposed, rats exhibited decreased premature
      and timeout responses after ethanol administration. Response latencies were not
      affected in AIE-exposed or control rats indicating no sedative effects of ethanol
      challenge. CONCLUSIONS: The results indicate that ethanol binge exposure during
      adolescence has long-lasting neurobehavioral consequences, which persist into
      adulthood and can be revealed after re-exposure to ethanol. AIE-induced
      diminished responses to the disruptive effects of ethanol on attention,
      impulsivity and cognitive flexibility may lead to increased alcohol drinking and
      other maladaptive behaviors in adulthood.

PMID- 21881873
TI  - Regulation of cocaine-induced reinstatement by group II metabotropic glutamate
      receptors in the ventral tegmental area.
AB  - RATIONALE: A high rate of relapse is a daunting challenge facing clinical
      treatment of cocaine addiction. Recent studies have shown that drugs of abuse
      enhance glutamate neurotransmission in dopamine neurons in the ventral tegmental
      area (VTA) and such enhancement may contribute to the risk of relapse.
      OBJECTIVES: Given the important role of group II metabotropic glutamate receptors
      (mGluR2/3s) in regulating glutamate release from the glutamatergic terminals,
      this study aimed to test whether activation of mGluR2/3s in the VTA can inhibit
      cocaine-induced reinstatement of cocaine-seeking behavior, a model of relapse to
      drug-seeking behavior. METHODS: Rats were trained to self-administer intravenous
      cocaine (0.25 mg/infusion) under a modified fixed-ratio 5 schedule. After rats
      reached the training criteria, they went through extinction training to
      extinguish cocaine-seeking behavior. Then the dose-response effects of a
      selective mGluR2/3 agonist LY 379268 microinjected into the VTA on cocaine
      induced reinstatement of cocaine-seeking behavior were assessed. RESULTS: LY
      379268 (0.032-0.1 MUg/side) dose-dependently decreased cocaine-induced
      reinstatement. The effect could not be fully attributed to diffusion of the drug
      to the neighboring substantia nigra or to motor impairment. Interestingly, LY
      379268 has a less potent effect on cocaine-induced reinstatement than on sucrose
      induced reinstatement of sucrose-seeking behavior. CONCLUSIONS: Our data support
      the idea that glutamate release in the VTA is critically involved in cocaine
      induced reinstatement and indicate that loss of mGluR2/3-mediated regulation of
      glutamate release in the VTA may critically contribute to the risk of relapse.

PMID- 21881874
TI  - Availability of dopamine and serotonin transporters in opioid-dependent users--a
      two-isotope SPECT study.
AB  - RATIONALE AND OBJECTIVE: The aims of this study were to examine the differences
      between 32 opioid-dependent users treated with a very low dose of methadone or
      undergoing methadone-free abstinence and 32 controls. METHODS: SPECT analysis
      using [(99m)Tc] TRODAT-1 to assess striatal dopamine transporter (DAT)
      availability and [(123)I] ADAM to assess midbrain serotonin transporter (SERT)
      availability were performed. RESULTS: Lower striatal DAT and midbrain SERT
      availabilities were noted in low-dose methadone users. History of metamphatamine
      use was associated with the lower striatal DAT. The striatal DAT of methadone
      free abstainers was also lower than controls. The midbrain SERT availability
      tended to be higher in the methadone-free abstainers than the low-dose methadone
      users. The severity of depressive symptoms was negatively correlated with
      midbrain SERT availability in the opioid users. CONCLUSION: The availability of
      striatal DAT tended to be, and the availability of midbrain SERT was, lower in
      the opioid users. History of metamphatamine use may confound the difference in
      straital DAT between controls and opioid users, as midbrain SERT and depressive
      symptoms are also associated with opioid use and abstinence.

PMID- 21881875
TI  - Developmental differences in ethanol-induced sensitization using postweanling,
      adolescent, and adult Swiss mice.
AB  - RATIONALE: The maturing adolescent brain has been suggested to be more sensitive
      than the adult brain to ethanol-induced neuroadaptations. In animal studies,
      sensitization to the stimulant effects of ethanol is used to study the
      vulnerability to chronic ethanol-induced neurobehavioral alterations. OBJECTIVES:
      The aim of the present study was to systematically characterize age-dependent
      changes in the development and expression of the sensitization to the stimulant
      effects of a range of ethanol doses in female Swiss mice. Three ages were
      studied: 21-day-old mice (postweanlings), 35-day-old mice (adolescents), and 63
      day-old mice (adults). METHODS: Postweanling, adolescent, and adult mice were
      daily injected with saline or various ethanol doses (1.5 to 4 g/kg) for 7 days.
      They were then tested for acute and sensitized locomotor activity. RESULTS:
      Postweanling and adolescent mice were more sensitive than adult mice to the acute
      stimulant effects of ethanol. In adult mice, daily injections of ethanol at doses
      between 2.5 and 4 g/kg led to significant sensitization. Higher ethanol doses
      (3.5 and 4 g/kg) were required to induce sensitization in postweanling and
      adolescent mice. However, younger mice showed ethanol sensitization of higher
      magnitude. CONCLUSIONS: Young mice develop very strong ethanol sensitization at
      doses that mimic binge drinking in humans. These results might explain why early
      ethanol drinking during adolescence is related to a higher prevalence of
      subsequent alcohol disorders.

PMID- 21881876
TI  - Despite aggressive histopathology survival is not impaired in young patients with
      colorectal cancer : CRC in patients under 50 years of age.
AB  - PURPOSE: Colorectal carcinoma (CRC) is generally a disease of persons older than
      50 years. Concerning younger patients, controversies still exist regarding
      features and prognosis of CRC. We performed this study to characterize CRC in
      young patients (<=50 years) as well as to evaluate outcome in comparison with
      older patients (>50 years) with CRC. METHODS: Clinical and histopathological
      parameters of 244 patients aged 50 years or less were compared with 1,718
      patients aged more than 50 years. RESULTS: Compared with older patients, the
      younger had less adenocarcinomas (82.8% vs. 89.1%; p = 0.004) and less
      postoperative complications (18.4% vs. 28.7%; p = 0.001), and less Union
      Internationale Contre le Cancer stage I colon cancers (22.9% vs. 13.6%, p =
      0.046) but elevated overall 5-year survival rates for M0 colon and rectal cancers
      (p = 0.005; p < 0.001). In young patients, the minority suffered from hereditary
      cancer syndromes (7.4%) and inflammatory bowel diseases (7.0%). Furthermore, up
      to 40% of young patients denied any cancers in their families. Cancer-related
      survival rates were significantly elevated in young patients with M0 rectal
      carcinoma (p = 0.014), whereas in M0 colon cancers, no differences were
      detectable (p = 0.542). In case of the presence of distant metastases, overall
      and cancer-related survival rates were similar in old and young patients.
      CONCLUSION: Although young patients present with more aggressive
      histopathological subtypes and less early stages, cancer-related survival is not
      less favourable compared with older patients.

PMID- 21881877
TI  - Patterns of care and survival for glioblastoma patients in the Veterans
      population.
AB  - Survival outcomes and patterns of care for brain tumor patients in the USA
      Veterans population have not been previously published and the extent of
      variation in outcomes between Veterans and the rest of the USA is currently
      unknown. The Veterans healthcare administration (VA) provides comprehensive care
      to Veterans and their families and maintains the Veterans affairs central cancer
      registry (VACCR). This was a retrospective review of microscopically-confirmed,
      supratentorial glioblastoma multiforme in male Veterans actively followed by the
      VACCR; survival was analyzed and compared to a national cohort from the
      surveillance, epidemiology and end results program. We analyzed 1,219 Veterans
      with glioblastomas diagnosed between 1997 and 2006. Median survival was 6.5
      months and 1, 2, and 5 years survival rates were 26.8, 5.4, and 0.5%,
      respectively. Patients receiving all three treatment modalities (surgical
      resection, radiotherapy, and chemotherapy) did best; these findings remained true
      among patients aged 70 and older such that these patients had an overall survival
      similar to those age <70. A comparable national cohort had longer median survival
      (9.0 months) and greater 1, 2, and 5 years survival rates (37.8, 12.8, and 4.1%)
      than the VA cohort. Survival and patterns of care are presented for the first
      time for Veterans with glioblastoma multiforme. In conclusion, we found that more
      aggressive therapy was associated with better survival, even among elderly
      Veterans and whether compared overall or by age group, VA patients showed
      decreased survival relative to a national cohort. We believe this potential
      disparity warrants further investigation.

PMID- 21881878
TI  - Fall field crickets did not acclimate to simulated seasonal changes in
      temperature.
AB  - In nature, many organisms alter their developmental trajectory in response to
      environmental variation. However, studies of thermal acclimation have
      historically involved stable, unrealistic thermal treatments. In our study, we
      incorporated ecologically relevant treatments to examine the effects of
      environmental stochasticity on the thermal acclimation of the fall field cricket
      (Gryllus pennsylvanicus). We raised crickets for 5 weeks at either a constant
      temperature (25 degrees C) or at one of three thermal regimes mimicking a
      seasonal decline in temperature (from 25 to 12 degrees C). The latter three
      treatments differed in their level of thermal stochasticity: crickets experienced
      either no diel cycle, a predictable diel cycle, or an unpredictable diel cycle.
      Following these treatments, we measured several traits considered relevant to
      survival or reproduction, including growth rate, jumping velocity, feeding rate,
      metabolic rate, and cold tolerance. Contrary to our predictions, the acclimatory
      responses of crickets were unrelated to the magnitude or type of thermal
      variation. Furthermore, acclimation of performance was not ubiquitous among
      traits. We recommend additional studies of acclimation in fluctuating
      environments to assess the generality of these findings.

PMID- 21881879
TI  - Novel therapies in MM: from the aspect of preclinical studies.
AB  - During the last decade, thalidomide, lenalidomide, and bortezomib have been
      approved by the US Food and Drug Administration for the treatment of MM; however,
      MM remains incurable. The development and progression of multiple myeloma (MM) is
      a complex multi-step process involving genetic abnormalities in tumor cells at
      both early and late stages. Moreover, soluble factors and cell-cell contact
      within the tumor bone marrow (BM) microenvironment promotes MM cell growth,
      survival, and drug resistance. A number of novel agents targeting both tumor
      cells and growth factors in the BM milieu have been developed. Currently they are
      under evaluation in preclinical studies, as single agents and/or in combination,
      to improve outcome of MM patients.

PMID- 21881880
TI  - Development and validation of a rapid method for microcystins in fish and
      comparing LC-MS/MS results with ELISA.
AB  - Microcystins (MCs) are the most common cyanotoxins found worldwide in freshwater,
      brackish, and marine environments. The rapid and accurate analysis of MCs and
      nodularin (Nod-R) in fish tissue is important for determining occurrence,
      following trends, and monitoring exposure for risk assessment and other purposes.
      The aim of this study was to develop a streamlined and reliable sample
      preparation method for eight MCs (MC-RR, MC-YR, MC-LR, MC-WR, MC-LA, MC-LY, MC
      LW, and MC-LF) and Nod-R in fish, and conduct a validation of the new method
      using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for analysis and
      compare the results with a commercial enzyme-linked immunosorbent assay (ELISA)
      kit. Different sample preparation methods were compared, and a simple extraction
      protocol with acidified acetonitrile/water (3:1) followed by hexane partitioning
      cleanup was found to be most effective. Thorough validation of the final method
      was conducted, and 90-115% recoveries were achieved for all analytes except for
      MC-RR, which gave 130% average recovery (isotopically labeled internal standards
      were unavailable to correct for possible biases). The use of electrospray
      ionization in the negative mode gave few interferences and minimal matrix effects
      in the LC-MS/MS analysis overall. Precision was typically 10-20% RSD among
      multiple days in experiments, detection limits were <10 ng/g in the fish tissue
      (catfish, basa, and swai filets), and no false-positives or false-negatives
      occurred in blind analyses of many spiked samples. The ELISA was unable to
      distinguish between MCs but was found to correctly assess the presence or absence
      of MCs and Nod-R in the blind-fortified fish tissues. The capability of these
      approaches to measure covalently bound MCs was not assessed.

PMID- 21881881
TI  - Fast DNA and protein microarray tests for the diagnosis of hepatitis C virus
      infection on a single platform.
AB  - Hepatitis C virus (HCV) is a major cause of chronic liver disease and liver
      cancer, and remains a large health care burden to the world. In this study we
      developed a DNA microarray test to detect HCV RNA and a protein microarray to
      detect human anti-HCV antibodies on a single platform. A main focus of this study
      was to evaluate possibilities to reduce the assay time, as a short time-to-result
      (TTR) is a prerequisite for a point-of-care test. Significantly reducing
      hybridisation and washing times did not impair the assay performance. This was
      confirmed first using artificial targets and subsequently using clinical samples
      from an HCV seroconversion panel derived from a HCV-infected patient. We were
      able to reduce the time required for the detection of human anti-HCV antibodies
      to only 14 min, achieving nanomolar sensitivity. The protein microarray exhibited
      an analytical sensitivity comparable to that of commercial systems. Similar
      results were obtained with the DNA microarray using a universal probe which
      covered all different HCV genotypes. It was possible to reduce the assay time
      after PCR from 150 min to 16 min without any loss of sensitivity. Taken together,
      these results constitute a significant step forward in the design of rapid,
      microarray-based diagnostics for human infectious disease, and show that the
      protein microarray is currently the most favourable candidate to fill this role.

PMID- 21881882
TI  - Osteosynthesis of femoral-neck nonunion with angle blade plate and autogenous
      fibular graft.
AB  - PURPOSE: Revision internal fixation for femoral-neck nonunion is a challenging
      procedure. Treatment options are osteotomy, osteosynthesis using various implants
      and grafting techniques (muscle pedicle, vascularised or nonvascularised fibular
      graft) or arthroplasty. The objective of this article is to report the outcome of
      revision internal fixation using an angle blade plate and autogenous fibular
      graft in symptomatic aseptic femoral-neck nonunion. METHODS: Twenty-two patients
      who had been treated previously with cannulated screws or dynamic hip screw for
      femoral-neck fracture and progressed to nonunion were treated with revision
      internal fixation using an angle blade plate and autogenous nonvascularised
      fibular graft. Mean patient age was 38 (range 21-52) years, with average duration
      between injury and revision surgery 11.2m (range 8-16 months). RESULTS: Other
      than one nonunion, we achieved union in all patients (21 patients, 91%) after an
      average period of 4.4 months. The functional outcome after 3.2 years as per
      scoring system given by Nagi et al.. showed excellent results in four, good in
      ten, fair in six and poor in two patients. Patients with poor results included
      one with nonunion and other with avascular necrosis with collapse of the femoral
      head. Average limb shortening was 1.5 cm, and mean femoral-neck-shaft angle was
      116 degrees . There was no instance of fibular graft fracture, slippage or
      implant cut-through. CONCLUSION: Angle blade plate provides rigid stability and
      offloads any shearing force over the fibular graft when used for revision
      internal fixation in aseptic femoral-neck nonunion. Thus, the fibular graft only
      serves the purpose of osteogenesis and stimulates the surrounding host cells to
      promote healing at the nonunion site. We recommend the angle blade plate and
      autogenous fibular graft as a viable option for hip-joint salvage in revision
      internal fixation of aseptic femoral-neck nonunion.

PMID- 21881883
TI  - Pin and plate fixation in complex distal humerus fractures: surgical technique
      and results.
AB  - PURPOSE: Complex distal humerus fractures are difficult to fix by conventional
      methods, especially in comminuted low distal humerus fractures. We propose a
      technique using small diameter K-wires and a plate on the humeral shaft. METHODS:
      Between May 2007 and March 2009, 19 patients with poor bone quality showing
      comminuted or low distal humerus fractures involving the articular surface were
      referred to our institution and were primarily treated by this technique that we
      called "pin and plate fixation". We have reviewed all the cases treated by this
      method. RESULTS: The average age was 46 years. All of the patients were followed
      up for a mean of 12 months and had a good range of motion (the average total arc
      of flexion-extension was 99 degrees ); the average Disabilities of the Arm,
      Shoulder and Hand (DASH) score was 18 points. The Mayo Elbow Performance Index
      was measured and the mean score was 88 in our patients. CONCLUSIONS: In this
      study, a technique has been evaluated for the treatment of complex distal humerus
      fractures. We recommend this technique in comminuted, osteoporotic or low distal
      humerus fractures in which other fixation methods seem difficult or even
      impossible.

PMID- 21881884
TI  - Medium-term results after total clavicle resection in cases of osteitis: a
      consecutive case series of five patients.
AB  - PURPOSE: Claviculectomy is a rare and poorly described event in the surgical
      therapy of diseases of the clavicle. We present a case series and functional
      results of patients who underwent total claviculectomy. METHODS: From 1995 to
      2006 a total of 26 patients diagnosed with osteitis of the clavicle underwent
      surgery in our unit. Of these, five patients (all female) needed a total
      resection of the clavicle in order to ensure permanent healing from infection.
      The data collection was prospective. The data gathered preoperatively and at
      follow-up included clinical examinations, laboratory findings, radiographs and
      the Constant shoulder scores. The mean follow-up period was 7.5 months. RESULTS:
      The surgical concept described was able to eliminate infection in all cases
      studied within an average hospital stay of 13.4 days (8-18 days). Only one
      patient showed complications; suffering from chronic pain syndrome requiring
      surgical revision. After total resection of the clavicle four of five patients
      showed very good functional results. The average Constant score showed a
      significant increase from 82 before surgery to 95 at follow-up. CONCLUSIONS: The
      surgical technique described for total claviculectomy, along with the insertion
      of local antibiotic beads, was able to eliminate infection in every case. Good
      functional results and a low complication rates were observed. For good
      functional results and the permanent elimination of infection, adjacent joints
      have to be addressed, the periosteal tube should be preserved and early
      functional treatment is essential.

PMID- 21881885
TI  - All-polyethylene tibial components in TKA in rheumatoid arthritis: a 25-year
      follow-up study.
AB  - PURPOSE: There is renewed interest in the all-polyethylene tibial component in
      total knee arthroplasty (TKA). Long-term results of this prosthesis in rheumatoid
      arthritis (RA) patients, however, are limited. Therefore, we studied 104 primary
      cemented all-polyethylene tibial TKA in 80 consecutive RA patients for up to 25
      years to determine the long-term survival of all-polyethylene tibial components
      in patients suffering from end stage RA. METHODS: We estimated revision rates
      according the revision rate per 100 observed component years used in national
      joint registries. Kaplan-Meier was used to estimate survival curves. RESULTS:
      During the 25-year follow-up, three revisions for tibial component loosening were
      performed. The mean revision rate of all-polyethylene tibial components with
      revision for aseptic loosening as the endpoint was 0.09 per 100 observed
      component years. This corresponds to a revision rate of 0.9% after ten years and
      2.25% after 25 years. Survivorship according to Kaplan-Meier was 100% at ten
      years and 87.5% at 25 years [95% confidence interval (CI) 64.6-100)]. CONCLUSION:
      This study shows good long-term results of all-polyethylene tibial TKA in
      patients with RA. RA patients with multiple-joint inflammation may be less
      physically active than osteoarthritis patients, resulting in a lower demand on
      the prosthesis, and these patients may, indeed, be good candidates for all
      polyethylene tibial TKA. Our results suggest that all-polyethylene tibial TKA
      could be a successful and cost-saving treatment for end-stage knee arthritis in
      RA patients.

PMID- 21881886
TI  - A systematic review of outcome and failure rate of uncemented Scandinavian total
      ankle replacement.
AB  - PURPOSE: The purpose of this study was to provide cumulative data about the
      intermediate to long-term outcome of Scandinavian total ankle replacement (STAR)
      in the literature and to provide a summary of survival rate, implant failure rate
      and reasons. METHODS: A comprehensive search for all relevant articles published
      in English and German from January 1995 to May 2011 was conducted. Two reviewers
      evaluated each study to determine whether it was eligible for inclusion and, if
      so, collected data of interest. The intermediate to long-term outcomes were
      determined. Evidence-based meta-analytic pooling of results across studies was
      performed to determine survival and failure rates. RESULTS: Sixteen primary
      studies with 2,088 implants were identified. The mean American Orthopaedic Foot
      and Ankle Society (AOFAS) score was 77.8 points, and the mean Kofoed ankle score
      was 76.4 points. The pooled mean five year survival rate was 85.9% [95%
      confidence interval (CI) 80.9-90.3], and the pooled mean ten year survival rate
      was 71.1% (95% CI 60.9-81.5). Pooled failure rate was 11.1% (95% CI 7.6 -14.9),
      with a mean follow-up time of 52 months; 41% failed within one year of initial
      operation. The first three reasons associated with implant failure were aseptic
      loosening (5.2%), malalignment (1.7%) and deep infection (1.0%). CONCLUSIONS: We
      found that STAR prosthesis achieved encouraging results in terms of intermediate
      to long-term outcome. The five and ten year survival rates were acceptable.
      However, the failure rate was still high. The major reasons for implant failure
      were aseptic loosening and malalignment. Maybe the increase of surgeons'
      experience and patient selection could improve outcomes and decrease failure
      rate.

PMID- 21881887
TI  - Evaluation of methods for achieving stable INR in healthy subjects during a
      multiple-dose warfarin study.
AB  - PURPOSE: No consistent method is available for finding stable warfarin
      maintenance doses and fast stabilization of international normalized ratio (INR)
      values among healthy subjects in experimental warfarin interaction studies. Using
      data from an earlier study that targeted a stable INR of 1.5-2.0 to test an
      interaction, we retrospectively evaluated potential dosing algorithms using all
      methods available to us to decrease the time needed for INR stabilization, which
      could be useful for future interaction studies in healthy subjects. METHODS:
      Published pharmacogenetic and clinical dosing algorithms used to initiate
      pharmacotherapy with warfarin were applied, predicted doses and actual doses were
      compared by regression analysis, and concentration-time profiles of S-warfarin
      were simulated using SimCYP(r) software. RESULTS: No demographic variables were
      significantly associated with time to reach a stable, low-intensity INR in this
      population of relatively young, healthy subjects. Predicted and actual doses were
      positively correlated for the pharmacogenetic algorithm, but not for the clinical
      algorithm. INR levels and S-warfarin concentrations were associated with CYP2C9
      and VKORC1 genotypes. CONCLUSIONS: Induction to a pharmacodynamic steady state
      for warfarin for future multiple-dose warfarin drug-interaction studies in
      healthy volunteers may be predicted using a pharmacogenetic-based dosing
      algorithm. Simulations revealed that the desired subtherapeutic INR level may be
      achieved by reducing the predicted dose by approximately 15%. Further study is
      needed to assess the applicability of this approach to decrease attrition rates
      and the time needed to reach INR stabilization.

PMID- 21881889
TI  - Reconstruction and verification of a genome-scale metabolic model for
      Synechocystis sp. PCC6803.
AB  - In terms of generating sustainable energy resources, the prospect of producing
      energy and other useful materials using cyanobacteria has been attracting
      increasing attention since these processes require only carbon dioxide and solar
      energy. To establish production processes with a high productivity, in silico
      models to predict the metabolic activity of cyanobacteria are highly desired. In
      this study, we reconstructed a genome-scale metabolic model of the cyanobacterium
      Synechocystis sp. PCC6803, which included 465 metabolites and 493 metabolic
      reactions. Using this model, we performed constraint-based metabolic simulations
      to obtain metabolic flux profiles under various environmental conditions. We
      evaluated the simulated results by comparing these with experimental results from
      (13)C-tracer metabolic flux analyses, which were obtained under heterotrophic and
      mixotrophic conditions. There was a good agreement of simulation and experimental
      results under both conditions. Furthermore, using our model, we evaluated the
      production of ethanol by Synechocystis sp. PCC6803, which enabled us to estimate
      quantitatively how its productivity depends on the environmental conditions. The
      genome-scale metabolic model provides useful information for the evaluation of
      the metabolic capabilities, and prediction of the metabolic characteristics, of
      Synechocystis sp. PCC6803.

PMID- 21881888
TI  - Antihypertensive effects and safety of eprosartan: a meta-analysis of randomized
      controlled trials.
AB  - PURPOSE: The benefits of reducing blood pressure (BP) have been well established,
      but uncertainty remains about the comparative effects of different BP-lowering
      regimens. We aimed to estimate the efficacy and the tolerability of eprosartan
      compared with other agents as monotherapy. METHODS: PubMed, EMBASE, and Cochrane
      Library were searched for relevant studies. A meta-analysis of randomized
      controlled trials (RCTs) meeting the criteria was performed using Review Manager
      and Stata/SE. RESULTS: Twenty-two articles were ultimately included out of 78
      studies, involving 6,460 patients. Eprosartan had a greater systolic blood
      pressure (SBP) reduction than placebo [weighted mean difference (WMD): 6.55, 95%
      confidence interval (CI) 4.86-8.25] and losartan (WMD: 2.24, 95% CI 0.08-4.40)
      and a greater diastolic blood pressure (DBP) reduction than placebo (WMD 3.95,
      95% CI 2.77-5.13). Therapeutic response rate of BP favored eprosartan [risk ratio
      (RR) 1.13, 95% CI 1.03-1.24] compared with enalapril. There were no statistical
      differences in SBP or DBP reductions comparing eprosartan with enalapril or
      telmisartan. Original RCTs included comparing eprosartan with valsartan and
      nitrendipine reported no differences in BP-lowering efficacy. CONCLUSIONS:
      Eprosartan monotherapy is equivalent to many first-line antihypertensive agents
      and is effective for the treatment of essential hypertension, especially for
      isolated systolic hypertension. The favorable efficacy and tolerability make
      eprosartan worthwhile to be taken into consideration by physicians.

PMID- 21881890
TI  - Temporal and spatial distribution of Bacillus and Clostridium histolyticum in
      swine manure composting by fluorescent in situ hybridization (FISH).
AB  - The temporal and spatial distribution of the genus Bacillus and Clostridium
      histolyticum group in swine manure composting was determined by fluorescent in
      situ hybridization using fluorescently labeled 16S rRNA-targeted oligonucleotide
      probes LGC353b and Chis150, respectively. The temporal distribution of total
      bacteria, Bacillus and C. histolyticum, detected in each layer of the composting
      pile was noticeable in that the number of them detected at the high-temperature
      stage was higher than that of the cooling stage. The number detected at the
      cooling stage was higher than that of the temperature-rising stage. The number of
      the total bacteria distributed in three locations achieved balance at the stage
      of cooling. The spatial distribution of the genus Bacillus cells was that the
      number and the relative abundance of Bacillus cells detected in the middle layer
      of composting pile were the lowest at each stage of composting. However, the
      minimum value of the relative abundance exceeded 8%. Compared with Bacillus spp.,
      the C. histolyticum group displayed higher relative abundance in the same layer
      at different stages of composting except in the top layer at the stage of high
      temperature. However, the characteristic of the spatial distribution was not
      noticeable. The detected limits of the genus Bacillus and C. histolyticum group
      were both found to be the high cell density of 10(6) cells g(-1) (wet weight).
      These results indicated that the genus Bacillus and C. histolyticum group were
      the predominant bacteria in the swine manure composting process and may play
      important role in this complex environment.

PMID- 21881891
TI  - Optimization of fixation methods for observation of bacterial cell morphology and
      surface ultrastructures by atomic force microscopy.
AB  - Fixation ability of five common fixation solutions, including 2.5%
      glutaraldehyde, 10% formalin, 4% paraformaldehyde, methanol/acetone (1:1), and
      ethanol/acetic acid (3:1) were evaluated by using atomic force microscopy in the
      present study. Three model bacteria, i.e., Escherichia coli, Pseudomonas putida,
      and Bacillus subtilis were applied to observe the above fixation methods for the
      morphology preservation of bacterial cells and surface ultrastructures. All the
      fixation methods could effectively preserve cell morphology. However, for
      preserving bacterial surface ultrastructures, the methods applying aldehyde
      fixations performed much better than those using alcohols, since the alcohols
      could detach the surface filaments (i.e., flagella and pili) significantly. Based
      on the quantitative and qualitative assessments, the 2.5% glutaraldehyde was
      proposed as a promising fixation solution both for observing morphology of both
      bacterial cell and surface ultrastructures, while the methonal/acetone mixture
      was the worst fixation solution which may obtain unreliable results.

PMID- 21881892
TI  - Active site analysis of cis-epoxysuccinate hydrolase from Nocardia tartaricans
      using homology modeling and site-directed mutagenesis.
AB  - Cis-epoxysuccinate hydrolase (CESH, EC 3.3.2.3) from Nocardia tartaricans is
      known to catalyze the opening of an epoxide ring of cis-epoxysuccinate (CES),
      thereby converting it to corresponding vicinal diol, L(+)-tartaric acid. An
      attempt has been made to build a 3D homology model of CESH to investigate the
      structure-function relationship, and also to understand the mechanism of the
      enzymatic reaction. Using a combination of molecular-docking simulation and
      multiple sequence alignment, a set of putative residues that are involved in the
      CESH catalysis has been identified. Functional roles of these putative active
      site residues were further evaluated by site-directed mutagenesis. Interestingly,
      the mutants D18A, D18E, Q20E, T22A, R55E, N134D, K164A, H190A, H190N, H190Q,
      D193A, and D193E resulted in complete loss of activity, whereas the mutants Y58F,
      T133A, S189A, and Y192D retained partial enzyme activity. Furthermore, the active
      site residues responsible for the opening of CES were analyzed, and the mechanism
      underlying the catalytic triad involved in L(+)-tartaric acid biosynthesis was
      proposed.

PMID- 21881893
TI  - Acetate scavenging activity in Escherichia coli: interplay of acetyl-CoA
      synthetase and the PEP-glyoxylate cycle in chemostat cultures.
AB  - Impairment of acetate production in Escherichia coli is crucial for the
      performance of many biotechnological processes. Aerobic production of acetate (or
      acetate overflow) results from changes in the expression of central metabolism
      genes. Acetyl-CoA synthetase scavenges extracellular acetate in glucose-limited
      cultures. Once converted to acetyl-CoA, it can be catabolized by the
      tricarboxylic acid cycle or the glyoxylate pathway. In this work, we assessed the
      significance of these pathways on acetate overflow during glucose excess and
      limitation. Gene expression, enzyme activities, and metabolic fluxes were studied
      in E. coli knock-out mutants related to the glyoxylate pathway operon and its
      regulators. The relevance of post-translational regulation by AceK-mediated
      phosphorylation of isocitrate dehydrogenase for pathway functionality was
      underlined. In chemostat cultures performed at increasing dilution rates, acetate
      overflow occurs when growing over a threshold glucose uptake rate. This threshold
      was not affected in a glyoxylate-pathway-deficient strain (lacking isocitrate
      lyase, the first enzyme of the pathway), indicating that it is not relevant for
      acetate overflow. In carbon-limited chemostat cultures, gluconeogenesis (maeB,
      sfcA, and pck), the glyoxylate operon and, especially, acetyl-CoA synthetase are
      upregulated. A mutant in acs (encoding acetyl-CoA synthetase) produced acetate at
      all dilution rates. This work demonstrates that, in E. coli, acetate production
      occurs at all dilution rates and that overflow is the result of unbalanced
      synthesis and scavenging activities. The over-expression of acetyl-CoA synthetase
      by cAMP-CRP-dependent induction limits this phenomenon in cultures consuming
      glucose at low rate, ensuring the recycling of the acetyl-CoA and acetyl
      phosphate pools, although establishing an energy-dissipating substrate cycle.

PMID- 21881894
TI  - CRP evolution pattern in CPAP-treated obstructive sleep apnea patients. Does
      gender play a role?
AB  - BACKGROUND-AIM: C-reactive protein (CRP) is directly implicated in atherogenesis
      and associated cardiovascular morbidity in patients with obstructive sleep apnea
      (OSA). Effective continuous positive airway pressure (CPAP) treatment has been
      shown to gradually decrease CRP levels and thus consequently improve disease
      related cardiovascular morbidity. However, the influence of gender on the CRP
      evolution pattern has never been assessed before. The aim of our study was to
      investigate possible gender differences in CRP evolution in OSA patients 3 and 6
      months after the start of effective CPAP treatment. METHODS: The study population
      consisted of 436 patients (252 males/184 females) with newly diagnosed moderate
      to severe OSA and good CPAP compliance assessed by a thorough follow up. High
      sensitivity C-reactive protein (hs-CRP) was assessed before CPAP initiation and
      at the third and sixth month of the follow-up period. RESULTS: C-reactive protein
      values showed a statistically significant decrease at the third and sixth month
      of CPAP therapy [initial values 0.79 +/- 0.65 mg/dL versus 0.70 +/- 0.52 mg/dL (p
      < 0.05) after 3 months and 0.30 +/- 0.33 mg/dL (p < 0.001) after 6 months of CPAP
      therapy]. When patients were divided into males and females, the above evolution
      pattern was changed. At the third month time point, the CRP values showed a
      statistically significant decrease only in males (from 0.74 +/- 0.53 mg/dL to
      0.61 +/- 0.5 mg/dL, p < 0.01) while females showed only minimal and insignificant
      changes (from 0.87 +/- 0.79 mg/dL to 0.83 +/- 0.51 mg/dL, p > 0.05). After 6
      months' treatment, CRP decreased significantly in both genders (males from 0.74
      +/- 0.53 mg/dL to 0.28 +/- 0.32 mg/dL, p < 0.001 and females from 0.87 +/- 0.79
      mg/dL to 0.34 +/- 0.36 mg/dL, p < 0.001). CONCLUSION: Our results suggest a delay
      in the normalization of CRP levels in females despite effective CPAP treatment. A
      time period of at least 6 months appeared to be required in women in order to
      reduce CRP levels and consequent cardiovascular risk. In contrast, CPAP's
      protective role in males is achieved at an earlier time point. Gender-related
      hormonal and genetic factors may influence the above CRP evolution pattern.

PMID- 21881896
TI  - Spontaneous recovery and ABC renewal from retroactive cue interference.
AB  - Two conditioned suppression experiments with rats were conducted to determine
      whether the spontaneous recovery and renewal that are commonly observed in
      retroactive outcome interference (e.g., extinction) also occur in retroactive cue
      interference. Experiment 1 showed that a long delay between Phase 2 (the
      interfering phase) and testing produces a recovery from the cue interference
      (i.e., the delay enhanced responding to the target cue trained in Phase 1), which
      is analogous to the spontaneous recovery effect observed in extinction and other
      retroactive outcome interference procedures. Experiment 2 showed that, when
      target and interfering cues are trained in separate contexts and testing occurs
      in a different but familiar context, a recovery from the cue interference is also
      observed (i.e., the context shift enhanced responding to the target), which is
      analogous to ABC renewal from extinction. The results are discussed in terms of
      the possibility that similar associative mechanisms underlie cue and outcome
      interference.

PMID- 21881897
TI  - Chemical and micromorphological properties of TSP and PM10 particles: case study
      in Bucharest urban area.
AB  - The purpose of this work was to determine some aspects of micromorphology of
      total suspended particles (TSP) and particulate matter with aerodynamic diameter
      <=10 MUm (PM(10)) and their major elemental components in order to highlight the
      main characteristics of the atmospheric particles from an urban environment,
      having a case study in the urban area of Bucharest. The sampling of PM(10) and
      TSP were conducted in the close vicinity of a high traffic road for 72 h per
      sample and also priority pollutants in air: Pb and Cd were quantified and
      correlations between their concentrations and local wind directions were also
      found. The parameters characterizing the micromorphology of particle-roughness of
      the particle surface and area of particle-were correlated with wind direction.

PMID- 21881898
TI  - Historical changes of sediments and mollusk assemblages in the Gulf of Batabano
      (Caribbean Sea) in the twentieth century.
AB  - The first paleoecological reconstruction of the biogeochemical conditions of the
      Gulf of Batabano, Caribbean Sea was performed from (210)Pb-dated sediment cores.
      Depth profiles of 20 major elements and trace metals, organic compounds, grain
      size, and mollusk assemblage composition were determined from 9 stations
      encompassing unconsolidated sediments in the gulf. Spatial heterogeneity was
      evident for the geochemistry of sediments and for the mollusk assemblage
      composition. Our reconstruction indicates that pollution is not a critical threat
      to the ecosystem, although a slight historical increase of lead enrichment factor
      was detected probably due to long-range atmospheric fallout. Mollusk assemblages
      were composed by 168 species belonging to 59 families and no temporal trends in
      the species diversity or assemblage composition were detected, suggesting no
      depletion of diversity or habitat loss. Other signals of habitat loss such as
      changes in organic budget or increase of fine sediment fraction were absent or
      weak. Nitrogen retained in sediments changed by <1% in the century, indicating no
      historical events of eutrophication or oligotrophication in the gulf. Historical
      decrease of fine sediment fraction in the eastern sector would be linked to
      modifications in sedimentation rate, land use, and/or particle transport from the
      shelf border; this also suggests that both sectors have different sedimentary
      dynamics. Although, on theoretical grounds, historical fishery may have caused
      deleterious ecosystem effects by overexploitation of spiny lobster stocks, no
      evidence of habitat degradation or loss, caused by fisheries, could be detected.

PMID- 21881899
TI  - Ecological assessment of French Atlantic lakes based on phytoplankton,
      phytobenthos and macrophytes.
AB  - Biological elements, including phytoplankton, phytobenthos, macrophytes, benthic
      invertebrates and fish, are employed by the EU Water Framework Directive (WFD)
      2000/60/EC as ecological indicators for the assessment of surface waters. The use
      of primary producers (phytoplankton, phytobenthos and macrophytes) for water
      quality assessment has a long history, and several methods have been developed
      worldwide. In this study, we used these three communities to assess the
      ecological status of five natural lakes located in the Aquitaine region
      (southwest France). Several biological indices used in lakes from other European
      countries or in French rivers were employed and compared among the three
      communities. Each primary producer provided complementary information about the
      ecological status of the lakes, including the invasiveness of exotic taxa.
      Regardless of the producer community used, the response to the environment, as
      reflected by the indices (adequate for each community), was similar: Lakes
      Cazaux, Lacanau and Hourtin showed the best ecological status and Parentis and
      Soustons the worst. Phytoplankton diagnosis reflected and integrated
      unambiguously the water quality of the lakes, as demonstrated by the strong
      relationships between the phytoplankton index and the trophic status criteria.
      This community appeared as the best indicator, especially when macrophytes were
      absent. The methods applied here represent a potential tool for the assessment of
      the ecological status in the context of WFD, but they need to be refined. We
      propose modifications for phytobenthos index initially tailored for running
      waters for adequate use in lentic ecosystems. Indices for the three primary
      producers should be modified to incorporate exotic species which may provide
      information on potential biodiversity losses.

PMID- 21881900
TI  - Characteristics of mining-ecological monitoring of environmental objects changing
      under the influence of toxic waste tailing dump ("Solnechny GOK" Company).
AB  - The article considers the characteristics of mining-ecological monitoring of
      environmental objects changing under the influence of toxic waste tailing dump
      (OAO "Solnechny GOK" Company).

PMID- 21881901
TI  - Bilateral assessment of functional tasks for robot-assisted therapy applications.
AB  - This article presents a novel evaluation system along with methods to evaluate
      bilateral coordination of arm function on activities of daily living tasks before
      and after robot-assisted therapy. An affordable bilateral assessment system
      (BiAS) consisting of two mini-passive measuring units modeled as three degree of
      freedom robots is described. The process for evaluating functional tasks using
      the BiAS is presented and we demonstrate its ability to measure wrist kinematic
      trajectories. Three metrics, phase difference, movement overlap, and task
      completion time, are used to evaluate the BiAS system on a bilateral symmetric
      (bi-drink) and a bilateral asymmetric (bi-pour) functional task. Wrist position
      and velocity trajectories are evaluated using these metrics to provide insight
      into temporal and spatial bilateral deficits after stroke. The BiAS system
      quantified movements of the wrists during functional tasks and detected
      differences in impaired and unimpaired arm movements. Case studies showed that
      stroke patients compared to healthy subjects move slower and are less likely to
      use their arm simultaneously even when the functional task requires simultaneous
      movement. After robot-assisted therapy, interlimb coordination spatial deficits
      moved toward normal coordination on functional tasks.

PMID- 21881902
TI  - Oscillator-based assistance of cyclical movements: model-based and model-free
      approaches.
AB  - In this article, we propose a new method for providing assistance during cyclical
      movements. This method is trajectory-free, in the sense that it provides user
      assistance irrespective of the performed movement, and requires no other sensing
      than the assisting robot's own encoders. The approach is based on adaptive
      oscillators, i.e., mathematical tools that are capable of learning the high level
      features (frequency, envelope, etc.) of a periodic input signal. Here we present
      two experiments that we recently conducted to validate our approach: a simple
      sinusoidal movement of the elbow, that we designed as a proof-of-concept, and a
      walking experiment. In both cases, we collected evidence illustrating that our
      approach indeed assisted healthy subjects during movement execution. Owing to the
      intrinsic periodicity of daily life movements involving the lower-limbs, we
      postulate that our approach holds promise for the design of innovative
      rehabilitation and assistance protocols for the lower-limb, requiring little to
      no user-specific calibration.

PMID- 21881903
TI  - Periparturition alterations to liver ultrasonographic echo-texture and fat
      mobilization parameters in clinically healthy Holstein cows.
AB  - The objective of present study was to record the sequential alterations in liver
      echo-texture through digital analyzing of the B-mode ultrasonography in three
      groups of under-conditioned (UC), moderate-conditioned (MC), and over-conditioned
      (OC) clinically healthy Holstein cows from 30 days to calving until 30 days in
      milk. Furthermore, to compare their changes in association with the changes of
      fat mobilization parameters of non-esterified fatty acids (NEFA),
      betahydroxybutyric acid (BHBA), and body condition score (BCS). Although the cows
      lost significant (P < 0.05) BCS from calving and the NEFA values showed an
      increasing trend near calving and the BHBA values significantly inclined
      postparturition, the mean grey scale histogram (MGSH) of liver images did not
      reveal significant fluctuations unless a significant decrease on calving day (P <
      0.05). The MGSH drop was predicted to be the result of anatomical changes in
      abdominal cavity, related to delivery and liver's blood flow. OC cows had higher
      NEFA on day +20 than UC and MC cows (P < 0.05). UC cows showed higher MGSH values
      on day -30 than MC cows and again on day -10 comparing to MC and OC cows (P <
      0.05). MGSH values correlated with BCS values (rUC = -0.186; rMC = -0.283; rOC = 
      0.158). It was concluded that the studied cows did not show significant
      alterations in textural changes in their liver ultrasound whilst going through
      fat mobilization. As quantitative ultrasonography has shown the potential to
      detect cases of fatty liver, it could gain the attention to become a feasible
      device for liver health monitoring on a herd basis.

PMID- 21881904
TI  - Phospholipid composition of plasma and erythrocyte membranes in animal species by
      31P NMR.
AB  - The aim of this study was to provide basal values of phospholipid (PL)
      composition in different animal species by 31P NMR analysis using detergents.
      This fast and accurate method allowed a quantitative analysis of PLs without any
      previous separation. Plasma and erythrocyte membrane PLs were investigated in
      mammals (pig, cow, horse). Moreover, for the first time, the composition of
      plasma PLs in avian (chicken and ostrich) was performed by 31P NMR. Significant
      qualitative and quantitative interspecies differences in plasma PL levels were
      found. Phosphatidilcholine (PC) and sphingomyelin (SPH) levels were significantly
      higher (P < 0.001) in chicken plasma than all the other species tested. In
      erythrocytes, cow PC and phosphatidylcholine diarachidoyl were significantly
      lower (P < 0.001) than for pigs and horses, whereas pig PC presented intermediate
      values among cows and horses. Inorganic phosphate and 2,3-diphosphoglycerate
      levels were also significantly different between the species under investigation.
      The [SPH/total PLs] molar ratios in erythrocytes confirmed interspecies
      differences in phospholipid composition while the PC/SPH molar ratios could be
      related to a distinct erythrocyte flexibility and aggregability. Diet and
      nutrition may contribute primarily to the interspecies differences in plasma PL
      amounts detected. Significant differences between chicken plasma PC and SPH
      levels and those of the other animal species could be ascribed to a fat
      metabolism specific to egg production.

PMID- 21881905
TI  - Increased variability of motor cortical excitability to transcranial magnetic
      stimulation in migraine: a new clue to an old enigma.
AB  - Increased, decreased or normal excitability to transcranial magnetic stimulation
      (TMS) has been reported in the motor (M1) and visual cortices of patients with
      migraine. Light deprivation (LD) has been reported to modulate M1 excitability in
      control subjects (CS). Still, effects of LD on M1 excitability compared to
      exposure to environmental light exposure (EL) had not been previously described
      in patients with migraine (MP). To further our knowledge about differences
      between CS and MP, regarding M1 excitability and effects of LD on M1
      excitability, we opted for a novel approach by extending measurement conditions.
      We measured motor thresholds (MTs) to TMS, short-interval intracortical
      inhibition, and ratios between motor-evoked potential amplitudes and supramaximal
      M responses in MP and CS on two different days, before and after LD or EL. Motor
      thresholds significantly increased in MP in LD and EL sessions, and remained
      stable in CS. There were no significant between-group differences in other
      measures of TMS. Short-term variation of MTs was greater in MP compared to CS.
      Fluctuation in excitability over hours or days in MP is an issue that, until now,
      has been relatively neglected. The results presented here will help to reconcile
      conflicting observations.

PMID- 21881906
TI  - Toxicity of pentachlorophenol to native aquatic species in the Yangtze River.
AB  - INTRODUCTION: While the literature is replete with studies of the toxic potency
      of pentachlorophenol (PCP), site-specific criteria for native aquatic species
      that can be used in ecological risk assessments has been lacking and application
      of toxicity information for non-native species is controversial. MATERIALS AND
      METHODS: In the present study, acute and chronic toxicities of PCP to six aquatic
      species native to the Yangtze River were determined. The HC5 and HC50 (hazardous
      concentration for 5% and 50% of species) were derived from dose-response curves
      for these native aquatic species and were then compared with those derived for
      non-native species. RESULTS: The acute toxicity values for the native species
      ranged from 8.8 * 10-2 mg l-1 (Plagiognathops microlepis) to 1.1 mg l-1
      (Soirodela polyrhiza), while chronic toxicity values based on no observed effect
      concentrations (NOECs) ranged from 0.01 mg l-1 (Macrobrachium superbum) to 0.25
      mg l-1 (Soirodela polyrhiza). Native aquatic benthos was more sensitive to acute
      PCP exposure than non-native species. There was no significant difference in
      NOECs derived from native fish species and those based on non-native fish
      species. The median acute HC5 and HC50 derived from the toxicity data of native
      taxa were both less than those derived from non-native taxa. There was no
      significant difference between chronic HC5s derived from the two sets of taxa.
      However, the median chronic HC50 derived from native taxa was less than that
      derived from non-native taxa. CONCLUSION: The study upon which we report here
      provides site-specific toxicity information developed for native species which
      can be used for the protection of local aquatic life from a common contaminant,
      PCP.

PMID- 21881907
TI  - Differential inflammatory responses triggered by toxic small molecules.
AB  - PURPOSE: The aim of this study is to determine whether exposure to hazardous
      chemicals alters chemokine or cytokine production in macrophages and link these
      events to changes in intracellular signaling pathways and activation of specific
      gene promoters. METHODS: RAW 264.7 mouse macrophages were treated with selected
      toxic industrial chemicals (TICs) and examined for changes in immune function.
      Luminex multiplex technology was used to assess changes in cytokine/chemokine
      expression and activation of kinase signaling pathways. In addition, a panel of
      macrophage cell lines with promoter-specific luciferase reporter genes were
      generated and treated with the TICs, and transcriptional responses to these
      chemicals were detected by changes in luminescence. RESULTS: Changes in
      expression of cytokines and chemokines were linked to changes in the activation
      state of intracellular signaling pathways. Overall, the findings reveal that
      sublytic levels of TICs can alter the profile of cytokines and chemokines
      expressed by macrophages, with a pattern that suggests immunosuppression. The
      data demonstrate that critical changes in immune function correlate with
      activation of kinase signaling pathways in macrophages. CONCLUSIONS: These data
      provide insight into the effects of sublytic doses of selected TICs on macrophage
      function, with a particular emphasis on identifying changes in expression of
      cytokines and chemokines. These altered patterns in immune function were linked
      to changes in the activation state of intracellular signaling pathways. The data
      strongly suggest that small amounts of TICs can have subtle, yet very critical,
      effects on macrophages.

PMID- 21881908
TI  - Regional, seasonal and interspecific variation in 15N and 13C in sympatric mouse
      lemurs.
AB  - Madagascar provides some of the rare examples where two or more primate species
      of the same genus and with seemingly identical niche requirements occur in
      sympatry. If congeneric primate species co-occur in other parts of the world,
      they differ in size in a way that is consistent with Hutchinson's rule for
      coexisting species, or they occupy different ecological niches. In some areas of
      Madagascar, mouse lemurs do not follow these "rules" and thus seem to violate one
      of the principles of community ecology. In order to understand the mechanisms
      that allow coexistence of sympatric congeneric species without obvious niche
      differentiation, we studied food composition of two identical sized omnivorous
      mouse lemur species, Microcebus griseorufus and M. murinus with the help of
      stable isotope analyses (delta(15)N and delta(13)C). The two species are closely
      related sister species. During the rich season, when food seems abundant, the two
      species do not differ in their nitrogen isotope composition, indicating that the
      two species occupy the same trophic level. But they differ in their delta(13)C
      values, indicating that M. griseorufus feeds more on C(4) and CAM (Crassulacean
      acid-metabolism) plants than M. murinus. During the lean season, M. murinus has
      lower delta(15)N values, indicating that the two species feed at different
      trophic levels during times of food shortage. Hybrids between the two species
      showed intermediate food composition. The results reflect subtle differences in
      foraging or metabolic adaptations that are difficult to quantify by traditional
      observations but that represent possibilities to allow coexistence of species.

PMID- 21881909
TI  - Pelagic crinoids (Roveacrinida, Crinoidea) discovered in the Neogene of Poland.
AB  - Until recently, it has been assumed that pelagic crinoids, the roveacrinids
      (Roveacrinida, Crinoidea), became extinct during the Cretaceous-Paleogene
      boundary event. Recent finds of well-preserved roveacrinidal remains (brachials
      and radials) in the Danian (Early Paleogene) of Poland showed that they survived
      into the earliest Cenozoic. This group was thus characterized as a "dead clade
      walking". Here, we present fossil evidence that these pelagic crinoids survived
      in Poland until at least the Middle Miocene (Badenian, ca. 14 Myr ago)-more than
      50 Myr after their supposed extinction. These Miocene roveacrinids constitute the
      first documented evidence of Roveacrinida in strata of Neogene age, thus
      prolonging the stratigraphic range of pelagic crinoids. This find characterizes
      the order as a "Lazarus taxon" rather than a "dead clade walking" group.

PMID- 21881910
TI  - Scientific production in cancer rehabilitation grows higher: a bibliometric
      analysis.
AB  - PURPOSE: The aim of the study was to evaluate scientific production in the field
      of cancer rehabilitation comparing publication trends and impact factor (IF)
      among countries. METHODS: The PubMed database was searched. Publications numbers
      and IF were evaluated both as absolute values and after standardization by
      population and gross domestic product (GDP). A dedicated software was developed
      to create a relational database containing all information about considered
      publications (Research Management System). RESULTS: Some 1,743 publications were
      retrieved from 1967 to 2008. Cancer rehabilitation publications have grown 11.6
      times, while the whole field of disease rehabilitation has grown 7.8 times.
      Breast neoplasms, squamous cell carcinoma, treatment outcome, endosseous dental
      implantation, follow-up studies, and surgical flaps were the most commonly used
      keywords. From 1994 to 2008, 946 citations were retrieved: 36.8% came from the
      European Union (EU) (Germany, the UK, and the Netherlands ranking at the top) and
      36.9% from the USA. The highest mean IF was reported for the USA (3.384) followed
      by Canada (3.265) and Australia (2.643). The EU has a mean IF of 0.839 with the
      Netherlands ranking first. Canada, Australia, and the USA had the best ratio
      between IF (sum) and resident population or GDP. CONCLUSIONS: Cancer
      rehabilitation is an expanding area with a growing scientific production. The
      rapidly ageing population, the higher number of cancer survivors, and the
      increasing need of resources for the after treatment of cancer patients
      contribute to explain the interest for this field.

PMID- 21881911
TI  - An overview of the European Society of Medical Oncology (ESMO) Symposium on
      Cancer and Nutrition 2009: from cancer prevention to nutrition support to
      alleviating suffering in patients with advanced cancer.

PMID- 21881912
TI  - Aerobic biotransformation of 2,4-dinitroanisole in soil and soil Bacillus sp.
AB  - 2,4-Dinitroanisole (DNAN) is a low sensitive melt-cast chemical being tested by
      the Military Industry as a replacement for 2,4,6-trinitrotoluene (TNT) in
      explosive formulations. Little is known about the fate of DNAN and its
      transformation products in the natural environment. Here we report aerobic
      biotransformation of DNAN in artificially contaminated soil microcosms. DNAN was
      completely transformed in 8 days in soil slurries supplemented with carbon and
      nitrogen sources. DNAN was completely transformed in 34 days in slurries
      supplemented with carbons alone and persisted in unamended microcosms. A strain
      of Bacillus (named 13G) that transformed DNAN by co-metabolism was isolated from
      the soil. HPLC and LC-MS analyses of cell-free and resting cell assays of
      Bacillus 13G with DNAN showed the formation of 2-amino-4-nitroanisole as the
      major end-product via the intermediary formation of the arylnitroso (ArNO) and
      arylhydroxylamino (ArNHOH) derivatives, indicating regioselective reduction of
      the ortho-nitro group. A series of secondary reactions involving ArNO and ArNHOH
      gave the corresponding azoxy- and azo-dimers. Acetylated and demethylated
      products were identified. Overall, this paper provides the evidence of fast DNAN
      transformation by the indigenous microbial populations of an amended soil with no
      history of contamination with explosives and a first insight into the aerobic
      metabolism of DNAN by the soil isolate Bacillus 13G.

PMID- 21881914
TI  - Pipeline embolization device (PED) for neurovascular reconstruction: initial
      experience in the treatment of 101 intracranial aneurysms and dissections.
AB  - INTRODUCTION: The purpose of this study was to evaluate the safety and efficacy
      of the recently available flow diverter "pipeline embolization device" (PED) for
      the treatment of intracranial aneurysms and dissections. METHODS: Eighty-eight
      consecutive patients underwent an endovascular treatment of 101 intracranial
      aneurysms or dissections using the PED between September 2009 and January 2011.
      The targeted vessels include 79 (78%) in the anterior circulation and 22 (22%) in
      the posterior circulation. We treated 96 aneurysms and 5 vessel dissections.
      Multiple devices were implanted in 67 lesions (66%). RESULTS: One technical
      failure of the procedure was encountered. Immediate exclusion of the target
      lesion was not observed. Angiographic follow-up examinations were carried out in
      80 patients (91%) with 90 lesions and revealed complete cure of the target
      lesion(s) in 47 (52%), morphological improvement in 32 lesions (36%), and no
      improvement in 11 lesions (12%). Six major complications were encountered: one
      fatal aneurysm rupture, one acute and one delayed PED thrombosis, and three
      hemorrhages in the dependent brain parenchyma. CONCLUSION: Our experience reveals
      that the PED procedure is technically straightforward for the treatment of
      selected wide-necked saccular aneurysms, fusiform aneurysms, remnants of
      aneurysms, aneurysms with a high likelihood of failure with conventional
      endovascular techniques, and dissected vessels. While vessel reconstruction,
      performed after dissection, is achieved within days, remodeling of aneurysmal
      dilatations may take several months. Dual platelet inhibition is obligatory.
      Parenchymal bleeding into brain areas dependent on the target vessel is uncommon.

PMID- 21881915
TI  - Phase I study of temsirolimus in combination with EKB-569 in patients with
      advanced solid tumors.
AB  - Purpose Activation of EGFR can stimulate proliferative and survival signaling
      through mTOR. Preclinical data demonstrates synergistic activity of combined EGFR
      and mTOR inhibition. We undertook a phase I trial of temsirolimus (T, an mTOR
      inhibitor) and EKB-569 (E, an EGFR inhibitor) to determine the safety and
      tolerability. Methods The primary aim was to determine the maximally tolerated
      dose (MTD) of this combination in adults with solid tumors. Following the dose
      escalation phase, (Cohort A), two subsequent cohorts were used to assess any
      pharmacokinetic (PK) interaction between the agents. Results Forty eight patients
      were enrolled. The MTD of this combination was E, 35 mg daily and T, 30 mg on
      days 1-3 and 15-17 using a 28-day cycle. The most common toxicities were nausea,
      diarrhea, fatigue, anorexia, stomatitis, rash, anemia, neutropenia,
      thrombocytopenia, and hypertriglyceridemia. Sixteen patients (36%) had at least
      one grade 3 toxicity. The most frequent grade 3/4 toxicities were diarrhea,
      dehydration, and nausea and vomiting (19% each). No grade 5 events were seen.
      Four patients had a partial response and 15 had stable disease. Clinical benefit
      was seen across a range of tumor types and in all cohorts. PK analysis revealed
      no significant interaction between E and T. Conclusions This combination of
      agents is associated with tolerable toxicities at doses that induced responses.
      PK studies revealed no interaction between the drugs. Further investigations of
      this targeting strategy may be attractive in renal cell carcinoma, non-small cell
      lung cancer, alveolar sarcoma, and carcinoid tumor.

PMID- 21881916
TI  - Anti-neoplastic agent thymoquinone induces degradation of alpha and beta tubulin
      proteins in human cancer cells without affecting their level in normal human
      fibroblasts.
AB  - The microtubule-targeting agents derived from natural products, such as vinca
      alkaloids and taxanes are an important family of efficient anti-cancer drugs with
      therapeutic benefits in both haematological and solid tumors. These drugs
      interfere with the assembly of microtubules of alpha/beta tubulin heterodimers
      without altering their expression level. The aim of the present study was to
      investigate the effect of thymoquinone (TQ), a natural product present in black
      cumin seed oil known to exhibit putative anti-cancer activities, on alpha/beta
      tubulin expression in human astrocytoma cells (cell line U87, solid tumor model)
      and in Jurkat cells (T lymphoblastic leukaemia cells). TQ induced a concentration
      and time-dependent degradation of alpha/beta tubulin in both cancer cell types.
      This degradation was associated with the up-regulation of the tumor suppressor
      p73 with subsequent induction of apoptosis. Interestingly, TQ had no effect on
      alpha/beta tubulin protein expression in normal human fibroblast cells, which
      were used as a non-cancerous cell model. These data indicate that TQ exerts a
      selective effect towards alpha/beta tubulin in cancer cells. In conclusion, the
      present findings indicate that TQ is a novel anti-microtubule drug which targets
      the level of alpha/beta tubulin proteins in cancer cells. Furthermore, they
      highlight the interest of developing anti-cancer therapies that target directly
      tubulin rather than microtubules dynamics.

PMID- 21881917
TI  - Biological evaluation of MR36, a novel non-polyglutamatable thymidylate synthase
      inhibitor that blocks cell cycle progression in melanoma cell lines.
AB  - Melanoma is one of the most common cancers, and its incidence has continued to
      increase over the past few decades. Chemotherapy resistance and related defects
      in apoptotic signaling are critical for the high mortality of melanoma. Effective
      drugs are lacking because apoptosis regulation in this tumor type is not well
      understood. The folate pathway has been considered an interesting target for
      anticancer therapies, and approaches targeting this pathway have recently been
      extended to melanoma treatment. In this study, the intracellular apoptosis
      signaling pathways of two melanoma cells lines (SK-MEL-2 and SK-MEL-28) were
      investigated after treatment with a new experimental antifolate substance (MR36)
      that targets thymidylate synthase. In both melanoma cell lines, apoptosis
      induction was triggered by a p53-independent mechanism. MR36-induced apoptosis
      was associated with a loss of both mitochondrial membrane potential and caspase-3
      activation. Induction of cell cycle arrest by MR36 was associated with changes in
      the expression of key cell cycle regulators, such as p21 and cyclin D1, and the
      hypophosphorylation of pRb. In addition, Fas signaling was also analyzed. These
      findings suggest that, unlike classical antifolates, MR36 exerted an inhibitory
      effect on both the enzymatic function and expression of thymidylate synthase,
      thereby inducing apoptosis through the activation of the extrinsic and intrinsic
      pathways in the melanoma cell lines. MR36 showed a different mechanism of action
      from the known antifolates (Nolatrexed and Pemetrexed) that resulted in higher
      anticancer activity. Therefore, MR36 should be included as a potential new
      therapeutic treatment in melanoma research.

PMID- 21881919
TI  - Comparison of QuantiFERON-TB Gold and the tuberculin skin test for the detection
      of previous tuberculosis infection evaluated by chest CT findings in Japanese
      rheumatoid arthritis patients.

PMID- 21881918
TI  - Phase I and pharmacokinetic study of dasatinib and cetuximab in patients with
      advanced solid malignancies.
AB  - BACKGROUND: Combined inhibition of epidermal growth factor receptor (EGFR) and
      Src family kinases (SFK) may lead to improved therapeutic effects. We evaluated
      the combination of dasatinib, an inhibitor of SFK and other kinases, and
      cetuximab, an anti-EGFR monoclonal antibody. PATIENTS AND METHODS: Patients with
      advanced solid malignancies received cetuximab intravenously on a standard weekly
      schedule and dasatinib orally, once daily at 3 dose levels: (1) 100 mg, (2) 150
      mg, (3) 200 mg. Pharmacokinetic and pharmacodynamic studies of dasatinib were
      performed prior to starting cetuximab and following 14 days of treatment.
      RESULTS: Twenty-five patients (3 dose level 1; 19 dose level 2; 3 dose level 3)
      were initially treated. Three patients developed dose-limiting toxicities: 1 at
      dose level 2 (headache) and 2 at dose level 3 (headache, nausea). Grade 3-4
      toxicities in more than 2 patients included: dyspnea (4), vomiting (4), nausea
      (3), hypersensitivity reactions (3), headache (3) and anemia (3). Twenty-one
      patients developed headache (8 grade 1; 10 grade 2), which occurred after the
      loading of cetuximab and lasted 1-3 days. Six additional patients were treated
      with dasatinib starting 3 days after the loading dose of cetuximab; none
      developed headache after dasatinib. Dasatinib pharmacokinetics and a transient
      decrease in SFK PY416 levels in peripheral blood mononuclear cells were not
      altered by cetuximab. Patients with higher plasma TGF-alpha levels had worse
      progression-free survival. CONCLUSIONS: Dasatinib 150 mg once daily plus weekly
      cetuximab is recommended for phase II studies. Early-onset headache was
      ameliorated by starting dasatinib after cetuximab.

PMID- 21881920
TI  - High and continuous exposure of laninamivir, an anti-influenza drug, may work
      suppressively to generate low-susceptibility mutants in animals.
AB  - Laninamivir octanoate (Inavir((r)); Daiichi Sankyo, Tokyo, Japan) is an anti
      influenza drug that provides complete treatment by a single inhalation. It works
      as a long-acting neuraminidase (NA) inhibitor by means of high and continuous
      exposure of laninamivir, its active metabolite, in the lungs of mice after
      intranasal administration. Even after 6 days after intranasal administration of
      236 MUg/kg laninamivir octanoate, the concentration of laninamivir in the lungs
      was maintained more than 2-3 orders higher than 50% inhibitory concentrations of
      laninamivir to N1 NAs, about 2 orders higher than N2 NA of seasonal influenza A
      viruses, and more than about 50 times higher than influenza B virus NA. From
      A/H1N1 influenza virus-infected and laninamivir octanoate-treated mice, no low
      susceptibility mutants to laninamivir were obtained. In contrast, four different
      mutants to oseltamivir were obtained from mice administered oseltamivir
      phosphate, which required repeated administration for treatment under the
      experimental condition, showing similar virus load reduction between both
      compounds. This finding suggested the unique characteristics of laninamivir
      octanoate in mice may work suppressively to generate low-susceptibility mutants.

PMID- 21881921
TI  - A 3,387 bp 5'-flanking sequence of the goat alpha-S1-casein gene provides correct
      tissue-specific expression of human granulocyte colony-stimulating factor (hG
      CSF) in the mammary gland of transgenic mice.
AB  - A new expression vector containing the 1,944 bp 5'-flanking regulatory region
      together with exon 1 and intron 1 of the goat alpha-S1-casein gene (CSN1S1), the
      full-sized human granulocyte colony-stimulating factor gene (hGCSF) and the 3'
      flanking sequence of the bovine CSN1S1, was created. The vector DNA was used for
      generation of four mouse transgenic lines. The transgene was integrated into
      chromosomes 8 and 12 of two founders as 2 and 5 copies, respectively. Tissue
      specific secretion of hG-CSF into the milk of transgenic mice was in the range of
      19-40 MUg/ml. RT-PCR analysis of various tissues of the transgenic mice
      demonstrated that expression of hGCSF was detected in only the mammary gland in
      the progeny of all founders. Moreover, cells were shown to be positive for hG-CSF
      by immunofluorescent analysis in the mammary glands but not in any other tissues.
      There were no signs of mosaic expression in the mammary gland. Trace amounts of
      hG-CSF were detected in the serum of females of two transgenic lines during
      lactation only. However, no transgenic mice showed any changes in hematopoiesis
      based on the number of granulocytes in blood. Immunoblotting of hG-CSF in the
      milk of transgenic mice revealed two forms, presumably the glycosylated and non
      glycosylated forms. The hematopoietic activity of hG-CSF in the milk of
      transgenic females is comparable to that of recombinant G-CSF. In general, the
      data obtained in this study show that the new expression vector is able to
      provide correct tissue-specific expression of hG-CSF with high biological
      activity in transgenic mice.

PMID- 21881922
TI  - Muscle-specific gene expression is underscored by differential stressor responses
      and coexpression changes.
AB  - Variations on the transcriptome from one skeletal muscle type to another still
      remain unknown. The reliable identification of stable gene coexpression networks
      is essential to unravel gene functions and define biological processes. The
      differential expression of two distinct muscles, M. flexor digitorum (FD) and M.
      psoas major (PM), was studied using microarrays in cattle to illustrate muscle
      specific transcription patterns and to quantify changes in connectivity regarding
      the expected gene coexpression pattern. A total of 206 genes were differentially
      expressed (DE), 94 upregulated in PM and 112 in FD. The distribution of DE genes
      in pathways and biological functions was explored in the context of system
      biology. Global interactomes for genes of interest were predicted. Fast/slow
      twitch genes, genes coding for extracellular matrix, ribosomal and heat shock
      proteins, and fatty acid uptake centred the specific gene expression patterns per
      muscle. Genes involved in repairing mechanisms, such as ribosomal and heat shock
      proteins, suggested a differential ability of muscles to react to similar
      stressing factors, acting preferentially in slow twitch muscles. Muscle
      attributes do not seem to be completely explained by the muscle fibre
      composition. Changes in connectivity accounted for 24% of significant
      correlations between DE genes. Genes changing their connectivity mostly seem to
      contribute to the main differential attributes that characterize each specific
      muscle type. These results underscore the unique flexibility of skeletal muscle
      where a substantial set of genes are able to change their behavior depending on
      the circumstances.

PMID- 21881923
TI  - Prognostic significance of NBS1 and Snail expression in esophageal squamous cell
      carcinoma.
AB  - BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy, but
      only limited molecular markers can predict its prognosis. Recently, a DNA double
      strand break repair protein Nijmegen breakage syndrome 1 (NBS1) was reported to
      induce Snail expression and predict poor prognosis in head and neck cancers.
      However, the clinicopathologic roles of NBS1 and Snail in ESCC remain unclear.
      METHODS: From January 1995 to September 1999, tissue samples from 153 patients
      with ESCC who underwent esophagectomies at our institutions were collected and
      made into tissue core arrays for study. Expression of NBS1 and Snail was examined
      by immunohistochemical staining. The clinicopathologic data were analyzed, and
      some additional studies were performed to explore the relationship between NBS1
      and Snail. RESULTS: NBS1 overexpression was observed in 28.1% (43/153) of ESCC,
      whereas Snail overexpression was observed in 26.1% (40/153) of ESCC.
      Overexpression of NBS1 correlated inversely with nodal status (P = 0.009) and was
      associated with better overall survival (P = 0.002). On the other hand,
      overexpression of Snail correlated positively with lymphovascular invasion (P =
      0.034) and was associated with worse overall survival (P = 0.036). Meanwhile,
      NBS1 overexpression correlated inversely with Snail overexpression marginally (P
      = 0.084). Using the Cox regression analysis, T status (P = 0.006), M status (P =
      0.008), and NBS1 overexpression (P = 0.007) were the independent factors of
      overall survival. CONCLUSIONS: Our results showed that NBS1 overexpression was an
      independent factor of better survival and Snail overexpression predicted a worse
      survival in ESCC. Combination of NBS1 plus Snail expression status could be used
      as a predictor of prognosis in ESCC.

PMID- 21881924
TI  - 2011 society of surgical oncology heritage award: honoring Kirby I. Bland, MD.

PMID- 21881925
TI  - Dizziness impairs health-related quality of life.
AB  - PURPOSE: Relatively little is known about the level of impairment in patients
      with dizziness. RESEARCH QUESTION: How much does dizziness impair the quality of
      life of patients referred to a multidisciplinary dizziness unit? PATIENTS AND
      METHODS: All 2,252 patients completed the Dutch version of the Dizziness Handicap
      Inventory (DHI-D; score 0-100 with higher scores representing more impairment).
      The results were classified into three categories: mild, moderate, and severe
      impairment. The three domains in the DHI representing physical, functional, and
      emotional aspects of dizziness were compared, as well as DHI scores of men versus
      women, between diagnoses, and the relationship between DHI and age. RESULTS: A
      total of 2,242 patients (64% women, mean age 54 years) completed the DHI with a
      mean score of 40.6. Almost 70% of patients had moderate or severe complaints. The
      handicap perceived by patients was primarily caused by physical and functional
      factors and less by emotional factors. Female patients and patients with
      hyperventilation syndrome and/or anxiety disorder had significantly higher DHI
      scores on all subscales. There was an S-shaped relationship between DHI score and
      age, and older patients reported more impairment. CONCLUSION: Dizziness has
      considerable impact on health-related quality of life of dizzy patients.

PMID- 21881927
TI  - Validation of Tikhonov adaptively regularized gamma variate fitting with 24-h
      plasma clearance in cirrhotic patients with ascites.
AB  - PURPOSE: The aim was to compare late-time extrapolation of plasma clearance (CL)
      from Tikhonov adaptively regularized gamma variate fitting (Tk-GV) and from mono
      exponential (E1) fitting. METHODS: Ten (51)Cr-ethylenediaminetetraacetic acid
      bolus IV studies in adults--8 with ascites--assessed for liver transplantation,
      with 12-16 plasma samples drawn from 5-min to 24-h, were fit with Tk-GV and E1
      models and CL results were compared using Passing-Bablok fitting. RESULTS: The 24
      h CL(Tk-GV) values ranged from 11.4 to 79.7 ml/min. Linear regression of 4-
      versus 24-h CL(Tk-GV) yielded no significant departure from a slope of 1, whereas
      the 4- versus 24-h CL(E1) slope, 1.56, was significantly increased. For CL(Tk-GV
      24-h) versus CL(E1-24-h), there was a biased slope and intercept (0.85, 5.97
      ml/min). Moreover, the quality of fitting of 24-h data was significantly better
      for Tk-GV than for E1, as follows. For 10 logarithm of concentration curves,
      higher r values were obtained for each Tk-GV fit (median 0.998) than for its
      corresponding E1 fit (median 0.965), with p < 0.0001 (paired t-test of z
      statistics from Fisher r-z transformations). The E1 fit quality degraded with
      increasing V/W [volume of distribution (l) per kg body weight, p = 0.003].
      However, Tk-GV fit quality versus V/W was uncorrelated (p = 0.8). CONCLUSION:
      CL(E1) values were dependent on sample time and the quality of fit was poor and
      degraded with increasing ascites, consistent with current opinion that CL(E1) is
      contraindicated in ascitic patients. CL(Tk-GV) was relatively more accurate and
      the good quality of fit was unaffected by ascites. CL(Tk-GV) was the preferred
      method for the accurate calculation of CL and was useful despite liver failure
      and ascites.

PMID- 21881926
TI  - Educational paper: Detection of child abuse and neglect at the emergency room.
AB  - The emergency room (ER) represents the main system entry for crises-based health
      care visits. It is estimated that 2% to 10% of children visiting the ER are
      victims of child abuse and neglect (CAN). Therefore, ER personnel may be the
      first hospital contact and opportunity for CAN victims to be recognised. Early
      diagnosis of CAN is important, as without early identification and intervention,
      about one in three children will suffer subsequent abuse. This educational paper
      provides the reader with an up-to-date and in-depth overview of the current
      screening methods for CAN at the ER. CONCLUSION: We believe that a combined
      approach, using a checklist with risk factors for CAN, a structured clinical
      assessment and inspection of the undressed patient (called 'top-toe' inspection)
      and a system of standard referral of all children from parents who attend the ER
      because of alcohol or drugs intoxication, severe psychiatric disorders or with
      injuries due to intimate partner violence, is the most promising procedure for
      the early diagnosis of CAN in the ER setting.

PMID- 21881928
TI  - [Use of intraosseus infusion in the German air rescue service : nationwide
      analysis in the time period 2005 to 2009].
AB  - BACKGROUND: Intraosseous infusion has become established as a fast and safe
      alternative to conventional vascular access in emergency situations. Originally
      the use of intraosseous access was limited to children up to 6 years of age and
      to adults for cardiopulmonary resuscitation but this limitation has now been
      removed. The aim of this study was to obtain data on mission reality regarding
      the use of intraosseous access in the prehospital setting against the background
      of the expanded recommendations on the use of the intraosseous infusion. METHODS:
      An analysis of rescue missions by all rescue helicopters of the ADAC (German
      Automobile Club) Air Rescue as well as the German Air Rescue Service (58
      helicopter emergency medical service bases) over a 4 year period from January
      2005 to December 2008 was carried out. RESULTS: A total of 247,454 rescue
      missions were carried out during the study period and in 525 patients (0.2% of
      the total study collective) an intraosseous access was established. There was a
      significant increase in the intraosseous infusion rate from 0.1% to 0.4%
      (p<0.05). Furthermore, there was a significant increase in its use in elderly
      patients and in patients with lower National Advisory Committee for Aeronautics
      (NACA) scores (2005 vs. 2008): 92.4% vs. 42.9% of all intraosseous infusions in
      patients  <= 6 years of age (p<0.05) and 74.4% vs. 42.9% of all intraosseous
      infusions in patients with NACA score VI/VII (p<0.05). The proportion of trauma
      patients in the total study collective was 33% and there was no significant
      change in the frequency of trauma cases over the study period but there was a
      remarkable increase of intraosseous infusions in trauma patients in the last year
      of the study period compared to the previous years (38% in 2008 vs. 27-30% in
      2005-2007). Furthermore, there was an increase in the number of different drug
      groups used for intraosseous infusion over the study period. CONCLUSIONS: The
      expanded indication recommendations for the use of intraosseous infusion in the
      prehospital setting enter more and more mission reality in air rescue services in
      Germany.

PMID- 21881929
TI  - [Removal of the laryngeal mask airway in the post-anesthesia care unit. A means
      of process optimization?].
AB  - BACKGROUND: Removal of the laryngeal mask airway in the post-anesthesia care unit
      could potentially contribute to a faster turnover from one operation to the next.
      The aim of this study was, therefore, to obtain an insight into the potential
      time saving and the safety of planned removal of the ProSealTM-LMA (PLMA) in the
      post-anesthesia care unit. METHODS: In this study 120 adult patients with
      American Society of Anesthesiologists (ASA) classification I-II, age range 18-85
      years, undergoing a surgical procedure under general anesthesia in which the PLMA
      was used were randomly assigned to one of two groups. In group I, the PLMA was
      removed in the awake patient in the operating room close to the end of the
      procedure. In group II, the anesthetised but spontaneously breathing patients
      were moved to the recovery room and the PLMA removed when the patient was awake.
      The anesthesia technique was standardized [balanced, sevoflurane, fentanyl,
      bispectral index-guided (BIS) target value=35+/-5] and identical in both groups
      until randomization. Patients were breathing room air during transport to the
      recovery room. Different time intervals as well as the incidence of critical
      incidents were compared between groups. An oxygen saturation (S(p)O(2)) value
      <95% was considered a clinically relevant and S(p)O(2) values <90% as clinically
      critical O(2)-desaturation. RESULTS: Removal of the PLMA took place after an
      average of 4.9+/-5.1 min in group I and after 19.5+/-9.6 min in group II. There
      was no difference in the availability of the anesthetist in the operating room
      for the following procedure between groups (group I: 12+/-5.6 min vs. group II:
      10.7+/-4.2 min, p>0.05) despite the fact that patients of group II left the
      operating room faster (4.9+/-3.9 min) than patients of group I (7.1+/-5.1 min,
      p<0.01). In group II patients were ready for discharge (White score=12) from the
      recovery room later (13.2+/-8.2 min) than in group I (3.6+/-4.8 min, p<0.01).
      There were no significant differences in other process related time intervals
      between group I and group II: duration of the operation (113.2+/-45.9 min vs.
      105.3+/-42.6 min), duration of dressing (5.1+/-3.7 min vs. 4.6+/-2.8 min),
      duration of transport to the recovery room (3.9+/-1.3 min vs. 3.6+/-1.3 min) and
      information at end of surgery by the surgeon (22.5+/-9.3 min vs. 22.4+/-10.5
      min). The incidence of clinically relevant as well as clinically critical O(2)
      desaturation at the time of recovery room arrival (S(p)O(2)<=90%) was increased
      in group II with 33.3% vs. 56.6% and 13.3% vs. 6.7%, p<0.01, respectively.
      CONCLUSION: Planned PLMA removal in the recovery room after BIS-guided balanced
      anesthesia did not enable the anesthetist to be available earlier for induction
      of anesthesia in the following patient. Hence the anesthetist could not
      contribute to a faster turnover of cases. Obviously, with the type of close
      communication between surgeon and anesthetist dictated by the study protocol
      (announcement of expected end of surgery by the surgeon 20 min before end of
      surgery) it is possible for the patient to regain consciousness within a very
      small time window following the end of surgery. Following this kind of protocol,
      postponement of removal of the LMA in the recovery room does not seem to be
      attractive neither from a clinical nor an economic point of view. In contrast,
      removal of LMA in the recovery room should be restricted to occasional cases with
      an abrupt end of the operation or prolonged emergence from anesthesia. The
      obvious risk of hypoxemia necessitates continuous O(2) application and S(p)O(2)
      monitoring during transport to the recovery room.

PMID- 21881930
TI  - [Do sociodemographic factors influence emergency medical missions? : analysis in
      the City of Munster].
AB  - BACKGROUND: Demographic development and changes in healthcare utilization have
      led to a rising number of calls for emergency services. In Germany life
      threatening situations are responded by physician-staffed ambulances in a 2-tier
      system whereas paramedic-staffed ambulances are dispatched in non-life
      threatening emergencies. A nationwide protocol guides dispatchers in triage
      decisions. In the years 1999 to 2009 a continuous rise in the number of calls for
      a physician-staffed ambulance in Munster was recorded. The degree of healthcare
      utilization according to socioeconomic status and age structure was
      retrospectively examined. METHODS: For the year 2006 all emergency calls in the
      City of Munster responded to by physician-staffed ambulances were analyzed. Each
      call was assigned to 1 of the 45 urban districts. The local incidence of
      emergency calls (calls/100 residents/year) was determined and compared to the
      socioeconomic status which was defined as the percentage of welfare and
      unemployment benefit recipients per district. Patient condition was assessed by
      the Munich National Advisory Committee for Aeronautics (M-NACA) score. This
      scoring system allows calls to be allocated to either life-threatening conditions
      or non-life-threatening conditions by objective vital parameters. The age
      structure of the emergency callers was also examined. RESULTS: Urban districts
      with a low socioeconomic status showed a higher incidence of emergency calls
      requiring physician-staffed ambulance responses than districts with a high
      socioeconomic status. Measured by the M-NACA scoring system, the fraction of life
      threatening emergencies among all calls proved to be equal to districts with a
      high socioeconomic status. A correlation between elderly patients and increasing
      numbers of life-threatening emergencies was found. CONCLUSIONS: A low
      socioeconomic status of an urban district will result in more ambulance
      responses. However, the proportion of life-threatening emergencies is equal to
      districts with a high socioeconomic status. Thus, the greater need for physician
      staffed ambulance responses matches clinical needs and legitimates current
      resource use in a 2-tier ambulance system. Indications for the abuse of physician
      staffed ambulances were not found. Considering an aging population the number of
      emergency calls will rise in the future.

PMID- 21881932
TI  - Sevoflurane to alleviate pain on propofol injection.
AB  - PURPOSE: Since the introduction of propofol, several drugs and methods have been
      used to alleviate the pain on its injection. This study was designed to evaluate
      the effect of adding sevoflurane 3% during preoxygenation in alleviation of pain
      on propofol injection. METHODS: In this randomized single-blinded study, 100
      patients were randomly allocated equally into five groups: sevoflurane-lidocaine
      tourniquet (SLT), sevoflurane-lidocaine (SL), lidocaine-tourniquet (LT),
      lidocaine (L), and sevoflurane (S). Approximately 10 min before the induction of
      anesthesia, midazolam 1-2 mg was administered intravenously to all patients. All
      patients received fentanyl 1 ug/kg as pretreatment and a full induction dose of
      propofol. A blinded anesthesia nurse assessed pain and hand movements throughout
      the injection of propofol. RESULTS: In the SLT group, all patients (100%) were
      pain free and had no hand movements. There was no significant difference in pain
      grade or in hand movements between the L and the S groups, or between the SLT and
      the SL groups. However, significant differences were observed in pain grade
      between the SLT and the L groups as well as between the SLT and the S groups. In
      addition, a significant difference in hand movement was observed only between the
      SLT and the S groups. CONCLUSION: The addition of 3% sevoflurane at the time of
      preoxygenation for 1 min along with routine use of lidocaine-tourniquet
      completely prevented pain upon propofol injection, whereas sevoflurane by itself
      provided similar analgesia to premixed lidocaine with propofol.

PMID- 21881933
TI  - Determinants of self medication practices among pregnant women in Ibadan,
      Nigeria.
AB  - OBJECTIVE: To assess the frequency and evaluate the factors underlining self
      medication with orthodox and herbal medicines among pregnant women in Ibadan,
      Nigeria. Setting Antenatal clinics at the major antenatal care facility in
      Ibadan, south-western Nigeria. METHODS: A prospective cross-sectional study with
      a pre-tested 15-item structured questionnaire over a 12 week period among 1,650
      pregnant women who attended antenatal clinics at a major antenatal care facility
      in Ibadan, south-western Nigeria. Data analysis was done with Chi-square,
      multivariate logistic regression and summary statistics. MAIN OUTCOME MEASURE:
      Frequency and major factors associated with self-medication in pregnancy.
      RESULTS: The response and completion rate was 96.6% (1,594) [mean age +/- SD 27
      +/- 5.3 years]. The majority of the respondents were literate (92.6%), self
      employed (61.5%) and in the third trimester (49.5%). A significant majority
      (63.8%) used self-medication (orthodox and herbal medicines) as their first
      response to perceived ill-health (P < 0.001). Self-medication in pregnancy was
      strongly associated with self-employment (OR: 3.8 (2.6-4.7), unemployment (OR:
      2.6 (1.4-4.2) and third trimester of pregnancy (OR: 4.2 (3.1-5.6). The major over
      the-counter medicines and potentially harmful prescription medicines kept at home
      for self-medication were Paracetamol, vitamins and haematinics; and piroxicam,
      dipyrone, chloramphenicol and Diazepam respectively. About one-third of the
      respondents who self-medicated (1,017) used local herbs (31.2%). The most
      frequent source of the medicines purchased during self-medication was patent
      medicine stores (55%). Mothers-in-law and relatives (41.3%) were the most
      frequently cited sources of advice during self-medication. Miscarriage/bleeding
      (44.3%) was the most frequently cited potential adverse effect that could occur
      with the use of certain medicines during pregnancy. Only 32% of respondents could
      identify medicines that are potentially harmful in pregnancy. CONCLUSION: Poorly
      guided self-medication with prescription, over-the-counter and herbal medicines
      is pervasive and significantly associated with gestational age and occupational
      pattern among pregnant women in Ibadan, south-western. A majority lacked the
      knowledge of potential adverse outcomes associated with the use of certain
      medicines, and the potentially harmful medicines to avoid during pregnancy.

PMID- 21881934
TI  - Gemfibrozil hepatotoxicity: a case report.
AB  - CASE DESCRIPTION: A 55-year-old woman was admitted to our hospital for management
      of thoracic trauma and bone fractures. One month after admission she started to
      receive gemfibrozil for hypertriglyceridemia. In the second month of admission,
      the patient complained of nausea and malaise. Laboratory value showed an acute
      hepatitis with raised AST, ALT. The abdominal ultrasound scan was normal, and
      viral serologic tests were negative. Gemfibrozil was discontinued and in a few
      days AST and ALT levels returned to normal. CONCLUSION: Gemfibrozil-induced
      hepatitis is a rare event but should be considered in the differential diagnoses
      of hepatitis in which no other obvious alternative cause is found.

PMID- 21881936
TI  - Rocky Mountain spotted fever: 'starry sky' appearance with diffusion-weighted
      imaging in a child.
AB  - We present a case of Rocky Mountain spotted fever encephalitis in a child imaged
      utilizing diffusion-weighted MRI. Although the imaging and clinical
      manifestations of this entity have been previously described, a review of the
      literature did not reveal any such cases reported in children utilizing diffusion
      weighted imaging. The imaging findings and clinical history are presented as well
      as a brief review of this disease.

PMID- 21881935
TI  - Altered FDG uptake patterns in pediatric lymphoblastic lymphoma patients
      receiving induction chemotherapy that includes very high dose corticosteroids.
AB  - BACKGROUND: Altered FDG uptake patterns were noted in certain lymphoblastic
      lymphoma patients during therapy. OBJECTIVE: To describe these altered FDG uptake
      patterns and their relationship to chemotherapy. MATERIALS AND METHODS: Thirty
      five FDG PET or PET/CT scans obtained in 11 children with lymphoblastic lymphoma
      were retrospectively reviewed. FDG uptake patterns were recorded. SUV
      measurements were performed in liver and facial soft tissues. Results were
      correlated with induction chemotherapy regimens. RESULTS: Six of the children had
      transiently altered FDG uptake with increased uptake in the superficial soft
      tissues, most notably involving the face. Altered uptake was noted approximately
      1 month after initiation of chemotherapy and subsequently resolved. Hepatic
      uptake was transiently reduced on the 1-month scan in all six children with
      increased facial uptake. No significant FDG uptake in lymphoma was seen on five
      of six scans with altered uptake; however, two of these five affected children
      had FDG uptake in lymphoma on the next follow-up examination. Blood glucose
      levels in the affected children were in the normal range. All six children with
      altered FDG uptake received the same induction chemotherapy regimen, which
      included very high doses of corticosteroids. CONCLUSIONS: Children with
      lymphoblastic lymphoma on induction chemotherapy protocols including very high
      doses of corticosteroids transiently demonstrated altered FDG uptake patterns,
      including increased superficial facial uptake and reduced hepatic uptake. The
      facial uptake is probably the FDG PET equivalent of Cushingoid facies. Caution in
      interpreting scans with this altered FDG uptake pattern is suggested, as uptake
      at sites of lymphomatous involvement may potentially be affected.

PMID- 21881937
TI  - Risk of myocardial infarction, stroke, and fracture in a cohort of community
      based breast cancer patients.
AB  - Clinical trials suggest that increased risk of osteoporosis and fracture are the
      only serious side effects of adjuvant aromatase inhibitors (AIs), but little is
      known regarding toxicities of AIs in non-trial populations. We evaluated whether
      use of AIs was associated with myocardial infarction, stroke, and fracture in a
      community-based population. Using data from the HealthCore Integrated Research
      Database, 44,463 women aged >= 50 years with >= 2 breast cancer diagnosis codes
      between 2001 and 2007 were followed through 2008. Of these, 44,026 were matched
      using propensity score methods to women aged >= 50 years with no breast cancer
      codes. We assessed whether treatment with AIs was associated with myocardial
      infarction, stroke, and fracture using Cox proportional hazards models with time
      varying treatment variables. Among breast cancer patients, 68.7% received no
      hormonal therapy, 20.6% received AIs (15.8% received only AIs, 4.8% were also
      treated with tamoxifen), and 10.7% received tamoxifen only. Breast cancer
      patients on AIs had a higher risk of any fracture (AHR = 1.13, 95% CI = 1.02
      1.25) than breast cancer patients not receiving hormonal therapy. Patients on
      tamoxifen had a lower risk of hip fracture (AHR = 0.51, 95% CI = 0.32-0.81) than
      breast cancer patients not receiving hormonal therapy. Rates of myocardial
      infarction and stroke for patients on AIs or tamoxifen did not differ
      significantly from breast cancer patients not on therapy. The side effect profile
      of AIs in this community-based population was similar to that seen in clinical
      trials. These findings provide reassurance that AIs appear to be associated with
      few serious side effects.

PMID- 21881939
TI  - Sequencing of the Tamus red mosaic virus genome: further evidence that it is a
      distinct species of the genus Potexvirus.
AB  - In 1993, a virus causing red mosaic and leaf distortion has been isolated from
      black bryony (Tamus communis) in Italy. Based on particle properties and
      serology, the virus was assigned to the genus Potexvirus and named Tamus red
      mosaic virus (TRMV), pending a genome sequence. The original Italian TRMV isolate
      was submitted to the DSMZ plant virus collection (PV-0397). To confirm the
      taxonomic status of the virus, the entire genome sequence was determined
      comprising 6,495 nucleotides excluding the poly(A)-tail. Five putative open
      reading frames (ORFs) in an arrangement typical for potexviruses were predicted.
      TRMV is closely related to but distinct from Clover yellow mosaic virus and
      Allium virus X. In addition to previous morphological and serological
      characterization, the results presented in this study further reinforce the
      classification of TRMV as a distinct virus species of the genus Potexvirus.

PMID- 21881938
TI  - Histologic findings in normal breast tissues: comparison to reduction mammaplasty
      and benign breast disease tissues.
AB  - Investigations of breast carcinogenesis often rely upon comparisons between
      cancer tissue and nonmalignant breast tissue. It is unclear how well common
      reference sources of nonmalignant breast tissues reflect normal breast tissue.
      Breast tissue samples were evaluated from three sources: (1) normal donor tissues
      in the Susan G. Komen for the Cure Tissue Bank at Indiana University Simon Cancer
      Center (KTB), (2) women who underwent reduction mammaplasty (RM) at Mayo Clinic
      Rochester, and (3) the Mayo Clinic Benign Breast Disease Cohort Study (BBD).
      Samples were examined histologically and assessed for proliferative disease and
      degree of lobular involution. Univariate comparisons were performed among the
      study groups, and multivariate analyses were performed with logistic regression
      to assess the association between study group and the presence of epithelial
      proliferative disease and complete lobular involution. Histologic data were
      collected for 455 KTB samples, 259 RM samples, and 319 BBD samples. Histologic
      findings and the frequency of epithelial proliferation were significantly
      different among the groups. Histologic abnormalities were seen in a minority of
      the KTB samples (35%), whereas an abnormality was present in 88% of RM tissues
      and 97.5% of BBD samples. The presence of proliferative disease (with or without
      atypical hyperplasia) was present in 3.3% of normal donors (3.3%), 17% of RM
      samples, and 34.9% of BBD samples (P < 0.0001 for each comparison). Multivariate
      analyses confirmed that these differences remained significant and also showed
      higher likelihood of complete lobular involution in the normal donor samples
      compared to RM and BBD tissues. Compared to benign breast disease tissues and
      reduction mammaplasty tissues, breast tissue samples from normal donors have
      significantly fewer histologic abnormalities and a higher frequency of more
      complete lobular involution. Breast tissue samples from normal donors represent a
      unique tissue resource with histologic features consistent with lower breast
      cancer risk.

PMID- 21881940
TI  - Genetic variability and evolutionary analyses of the coat protein gene of Tomato
      mosaic virus.
AB  - Tomato mosaic virus (ToMV), a member of the genus Tobamovirus, infects several
      ornamental and horticultural crops worldwide. In this study, the nucleotide
      sequences of the coat protein gene of worldwide ToMV isolates were analyzed to
      estimate the genetic structure and diversity of this virus and the involved
      evolutionary forces. The phylogenetic analysis showed three clades with high
      bootstrap support: Clade I contained three ToMV isolates from Brazil collected
      from pepper, Clade II comprised one Brazilian ToMV isolate from pepper, and Clade
      III was composed of ToMV isolates collected from different plant hosts (pepper,
      tomato, eggplant, lilac, camellia, dogwood, red spruce, etc.) and water (from
      melting ice, lakes and streams) from different countries: USA, Brazil, Korea,
      Germany, Spain, Denmark (Greenland), China, Taiwan, Malaysia, Iran, and
      Kazakhstan. With the exception of Brazil, nucleotide diversity within and between
      different geographic regions was very low, although statistical analyses
      suggested some gene flow between most of these regions. Our analyses also
      suggested a strong negative selection which could have contributed to the genetic
      stability of ToMV.

PMID- 21881941
TI  - The convergent evolution of neural substrates for cognition.
AB  - This review describes a case of convergence in the evolution of brain and
      cognition. Both mammals and birds can organize their behavior flexibly over time
      and evolved similar cognitive skills. The avian forebrain displays no lamination
      that corresponds to the mammalian neocortex; hence, lamination does not seem to
      be a requirement for higher cognitive functions. In mammals, executive functions
      are associated with the prefrontal cortex. The corresponding structure in birds
      is the nidopallium caudolaterale. Anatomic, neurochemical, electrophysiologic and
      behavioral studies show these structures to be highly similar, but not
      homologous. Thus, despite the presence (mammals) or the absence (birds) of a
      laminated forebrain, 'prefrontal' areas in mammals and birds converged over
      evolutionary time into a highly similar neural architecture. The
      neuroarchitectonic degrees of freedom to create different neural architectures
      that generate identical prefrontal functions seem to be very limited.

PMID- 21881942
TI  - Effects of acyl-CoA:diacylglycerol acyl transferase 1 (DGAT1) gene on milk
      production traits in crossbred Holstein dairy cattle.
AB  - The objective of this study was to analyze and investigate the genotype frequency
      and the association between Acyl-CoA:diacylglycerol acyltransferase1 gene, DGAT1
      gene, and milk yield (MY), milk composition, protein yield (PY), fat yield (FY),
      solid not fat yield (SNF), total solid (TS), the content of fat, protein, solid
      not fat, and total solid, (%Fat,%Prot,%SNF,%TS) in two herds of crossbred
      Holstein dairy cattle in Thailand. Two hundred and twenty-seven crossbred
      Holstein cows were used and their blood samples were taken for the study. PCR
      RFLP was used to identify the allele and genotype of DGAT1 gene. A general linear
      model and the least square method were used to estimate the least square mean and
      additive, and the dominant effect of the gene on the traits and the least
      significant differences were used to compare the mean of each trait between
      genotypes. Two alleles (K, A) and three genotypes (AA, KA, KK) were detected, the
      highest allele and genotype frequencies were A and AA, respectively. The least
      mean squares of each genotype were compared and significant differences between
      genotype were detected. Genotype KK has the greatest effect on all milk
      composition content traits, while genotype AA has the greatest effect on yield
      traits. Highly significant additive gene effect was detected. From the results,
      it can be concluded that the DGAT1 gene can be used as a gene marker for assisted
      selection in milk composition traits.

PMID- 21881943
TI  - Culturability and persistence of Francisella noatunensis subsp. orientalis (syn.
      Francisella asiatica) in sea- and freshwater microcosms.
AB  - Francisella noatunensis subsp. orientalis (syn. Francisella asiatica), the
      causative agent of franciselliosis in warm-water fish, is a Gram-negative
      facultative intracellular bacterium. Although it has been characterized as one of
      the most pathogenic bacteria in fish, the water conditions that allow for its
      survival and infectious capacities outside the fish host are not known. Data
      obtained in this project indicate that both temperature and salinity are
      important factors in the culturability and persistence of F. noatunensis subsp.
      orientalis in both sea- and freshwater microcosms. These results indicate that
      culturable F. noatunensis subsp. orientalis persist for longer periods of time
      and at higher numbers in seawater, and its persistence is inversely related to
      water temperature. Moreover, the pathogenic properties of the bacteria suspended
      in water microcosms appear to decrease after only 24 h and become non-infective
      after 2 days in the absence of the fish host.

PMID- 21881944
TI  - A molecular enrichment strategy based on cpn60 for detection of epsilon
      proteobacteria in the dog fecal microbiome.
AB  - Members of the rare microbiome can be important components of complex microbial
      communities. For example, pet dog ownership is a known risk factor for human
      campylobacteriosis, and Campylobacter is commonly detected in dog feces by
      targeted assays. However, these organisms have not been detected by metagenomic
      methods. The goal of this study was to characterize fecal microbiota from healthy
      and diarrheic pet dogs using two different levels of molecular detection. PCR
      amplification and pyrosequencing of the universal cpn60 gene target was used to
      obtain microbial profiles from each dog. To investigate the relatively rare
      epsilon-proteobacteria component of the microbiome, a molecular enrichment was
      carried out using a PCR that first amplified the cpn10-cpn60 region from epsilon
      proteobacteria, followed by universal cpn60 target amplification and
      pyrosequencing. From the non-enriched survey, the major finding was a
      significantly higher proportion of Bacteroidetes, notably Bacteroides vulgatus,
      in healthy dogs compared to diarrheic dogs. Epsilon-proteobacteria from the
      genera Helicobacter and Campylobacter were also detected at a low level in the
      non-enriched profiles of some dogs. Molecular enrichment increased the proportion
      of epsilon-proteobacteria sequences detected from each dog, as well as identified
      novel, presumably rare sequences not seen in the non-enriched profiles. Enriched
      profiles contained known species of Arcobacter, Campylobacter, Flexispira, and
      Helicobacter and identified two possibly novel species. These findings add to our
      understanding of the canine fecal microbiome in general, the epsilon
      proteobacteria component specifically, and present a novel modification to
      traditional metagenomic approaches for study of the rare microbiome.

PMID- 21881945
TI  - Biological activity of selected Lamiaceae and Zingiberaceae plant essential oils
      against the dengue vector Aedes aegypti L. (Diptera: Culicidae).
AB  - The larvicidal activity of hydrodistillate extracts from Mentha piperita L.
      Ocimum basilicum L. Curcuma longa L. and Zingiber officinale L. were investigated
      against the dengue vector Aedes aegypti L. (Diptera: Culicidae).The results
      indicated that the mortality rates at 80, 100, 200 and 400 ppm of M. piperita, Z.
      officinale, C. longa and O. basilicum concentrations were highest amongst all
      concentrations of the crude extracts tested against all the larval instars and
      pupae of A. aegypti. Result of log probit analysis (at 95% confidence level)
      revealed that lethal concentration LC50 and LC90 values were 47.54 and 86.54 ppm
      for M. piperita, 40.5 and 85.53 ppm for Z. officinale, 115.6 and 193.3 ppm for C.
      longa and 148.5 and 325.7 ppm for O. basilicum, respectively. All of the tested
      oils proved to have strong larvicidal activity (doses from 5 to 350 ppm) against
      A. aegypti fourth instars, with the most potent oil being M. piperita extract,
      followed by Z. officinale, C. longa and O. basilicum. In general, early instars
      were more susceptible than the late instars and pupae. The results achieved
      suggest that, in addition to their medicinal activities, Lamiaceae and
      Zingiberaceae plant extracts may also serve as a natural larvicidal agent.

PMID- 21881946
TI  - Comparative studies on animal models for Opisthorchis viverrini infection: host
      interaction through susceptibility and pathology.
AB  - Syrian hamsters and gerbils are animal models for Opisthorchis viverrini
      infection. In both models, the parasites develop into adults with different
      pathologies of the hepatobiliary system. However, no comparative pathological
      studies have yet been completed. We therefore investigated host interaction
      through the susceptibility and pathological changes of Syrian hamsters and
      gerbils infected with 50 O. viverrini metacercariae for 30, 60, and 90 days post
      infection. Animals were sacrificed at each time point for comparative study.
      Susceptibility and infectivity were investigated through worm burden. Parasite
      morphology and reproductive organs were stained with carmine and observed under
      light microscopy. Reproductive organs and eggs per worm were counted to confirm
      worm maturity. Bile acid components of both animal groups were analyzed by thin
      layer chromatography. The results showed that infection in gerbils was of greater
      severity than in Syrian hamsters by observation of bile obstruction, enlargement
      of the gallbladder and common bile duct, and generation of fibrosis and
      cirrhosis. The worm burden of infected gerbils was lower than that observed in
      Syrian hamsters. Infectivity in both Syrian hamsters and gerbils was 100% with
      infection by 50 metacercariae; whereas with 10 metacercariae, the infectivity in
      gerbils was zero to very low, but still 100% in Syrian hamsters. The largest body
      size of worms, and the largest ovary and testes areas, was correlated with eggs
      per gram of feces and eggs per worm. The bile acid components cholic acid and
      chenodeoxycholic acid were undetectable in gerbils. The present study suggests
      that although Syrian hamsters, usually the host selection for an animal model,
      are susceptible to O. viverrini infection, infected gerbils produce worms that
      mature more rapidly, have larger body sizes, and more fully developed
      reproductive organs; this may be caused by the difference in bile acid
      components.

PMID- 21881947
TI  - Biting and bloodsucking lice of dogs--treatment by means of a neem seed extract
      (MiteStop(r), Wash Away Dog).
AB  - Dogs infested with lice belonging either to the group of Mallophaga (hairlings,
      i.e., Trichodectes canis) or Anoplura (bloodsucking lice, e.g., Linognathus
      setosus) were washed with the neem seed preparations MiteStop(r) or Wash Away
      Dog. It was found that a single treatment with one of these products killed both
      motile stages and those developing inside eggs (nits) being glued at the hair. In
      both cases the product had been left for 20 min onto the hair before it was
      washed away just with normal tap water.

PMID- 21881949
TI  - Modulation of dendritic cells and toll-like receptors by marathon running.
AB  - The focus of this study was to assess exercise-induced alterations of circulating
      dendritic cell (DC) subpopulations and toll-like receptor (TLR) expression after
      marathon running. Blood sampling was performed in 15 obese non-elite (ONE), 16
      lean non-elite (LNE) and 16 lean elite (LE) marathon runners pre- and post
      marathon as well as 24 h after the race. Circulating DC-fractions were measured
      by flow-cytometry analyzing myeloid DCs (BDCA-1+) and plasmacytoid DCs (BDCA-2+).
      We further analyzed the (TLR) -2/-4/-7 in peripheral blood mononuclear cells (rt
      PCR/Western Blot) and the cytokines CRP, IL-6, IL-10, TNF-alpha and oxLDL by
      ELISA. After the marathon, BDCA-1 increased significantly in all groups [LE
      (pre/post): 0.35/0.47%; LNE: 0.26/0.50% and ONE: 0.30/0.49%; all p < 0.05]. In
      contrast, we found a significant decrease for BDCA-2 directly after the marathon
      (LE: 0.09/0.01%; LNE: 0.12/0.03% and ONE: 0.10/0.02%; all p < 0.05). Levels of
      TLR-7 mRNA decreased in all groups post-marathon (LE 44%, LNE 67% and ONE 52%;
      all p < 0.01), with a consecutive protein reduction (LE 31%, LNE 52%, ONE 42%;
      all p < 0.05) 24 h later. IL-6 and IL-10 levels increased immediately after the
      run, whereas increases of TNF-alpha and CRP-levels were seen after 24 h. oxLDL
      levels remained unchanged post-marathon. In our study population, we did not find
      any relevant differences regarding training level or body weight. Prolonged
      endurance exercise induces both pro- and anti-inflammatory cytokines. Anti
      inflammatory cytokines, such as IL-10, may help to prevent excessive oxidative
      stress. Marathon running is associated with alterations of DC subsets and TLR
      expression independent of training level or body weight. Myeloid and plasmacytoid
      DCs are differently affected by the excessive physical stress. Immunomodulatory
      mechanisms seem to play a key role in the response and adaptation to acute
      excessive exercise.

PMID- 21881950
TI  - The energetics of ultra-endurance running.
AB  - Our objective was to determine the effects of long-lasting endurance events on
      the energy cost of running (C(r)), and the role of maximal oxygen uptake
      (VO(2max)), its fractional utilisation (F) and C(r) in determining the
      performance. Ten healthy runners (age range 26-59 years) participated in an ultra
      endurance competition consisting of three running laps of 22, 48 and 20 km on
      three consecutive days in the North-East of Italy. Anthropometric characteristics
      and VO(2max) by a graded exercise test on a treadmill were determined 5 days
      before and 5 days after the competition. In addition, C(r) was determined on a
      treadmill before and after each running lap. Heart rate (HR) was recorded
      throughout the three laps. Results revealed that mean C(r) of the individual laps
      did not increase significantly with lap number (P = 0.200), thus ruling out any
      chronic lap effect. Even so, however, at the end of lap 3, C(r) was 18.0% (P <
      0.001) greater than before lap 1. In addition, a statistically significant acute
      lap effect on C(r) was observed at the end of the second and third laps (by 11.4
      and 7.2%, respectively). The main factors determining performance were VO(2max),
      F, as estimated from the average HR, and the average C(r-mean) throughout the
      three laps; the grand average speed over the three laps being described by v (end
      mean) = F * VO(2max) * C(r-mean)(-1). We concluded that (1) the substantial
      increase of C(r-mean) during the competition yields to marked worsening of the
      performance, and (2) the three variables F, VO(2max) and C(r-mean) combined as
      described above explaining 87% of the total competition time variance.

PMID- 21881951
TI  - Diversity of MHC class I haplotypes in cynomolgus macaques.
AB  - Cynomolgus macaques are widely used as a primate model for human diseases
      associated with an immunological process. Because there are individual
      differences in immune responsiveness, which are controlled by the polymorphic
      nature of the major histocompatibility (MHC) locus, it is important to reveal the
      diversity of MHC in the model animal. In this study, we analyzed 26 cynomolgus
      macaques from five families for MHC class I genes. We identified 32 Mafa-A, 46
      Mafa-B, 6 Mafa-I, and 3 Mafa-AG alleles in which 14, 20, 3, and 3 alleles were
      novel. There were 23 MHC class I haplotypes and each haplotype was composed of
      one to three Mafa-A alleles and one to five Mafa-B alleles. Family studies
      revealed that there were two haplotypes which contained two Mafa-A1 alleles.
      These observations demonstrated further the complexity of MHC class I locus in
      the Old World monkey.

PMID- 21881948
TI  - Parasitic infections and myositis.
AB  - Infectious myositis may be caused by a wide variety of bacterial, fungal, viral,
      and parasitic agents. Parasitic myositis is most commonly a result of
      trichinosis, cystericercosis, or toxoplasmosis, but other parasites may be
      involved. A parasitic cause of myositis is suggested by history of residence or
      travel to endemic area and presence of eosinophilia. The diagnosis of parasitic
      myositis is suggested by the clinical picture and radiologic imaging, and the
      etiologic agent is confirmed by parasitologic, serologic, and molecular methods,
      together with histopathologic examination of tissue biopsies. Therapy is based on
      the clinical presentation and the underlying pathogen. Drug resistance should be
      put into consideration in different geographic areas, and it can be avoided
      through the proper use of anti-parasitic drugs.

PMID- 21881952
TI  - Characterisation of MHC haplotypes in a breeding colony of Indonesian cynomolgus
      macaques reveals a high level of diversity.
AB  - Recent reports have revealed that cynomolgus macaques obtained from different
      geographic origins may be more or less suitable for particular studies depending
      on the specific question(s) being addressed, e.g. Mauritian cynomolgus macaques
      are particularly suitable for detailed immunological studies against a limited
      genetic background while less conserved populations may be more appropriate to
      predict breadth of vaccine coverage in the genetically diverse human population.
      We have characterised MHC haplotypes in 90 Indonesian cynomolgus macaques using
      microsatellite and reference strand conformational analysis. Thirty unique
      haplotypes were defined in the cohort, emphasising the high degree of diversity
      in this population of cynomolgus macaques. The majority of haplotypes were
      present at a frequency of <= 6%. Transcription profiles indicated that each
      haplotype was associated with two to eight transcribed class I alleles. The
      results corroborate previous reports of the extensive MHC diversity of Indonesian
      cynomolgus macaques and provide additional data to inform colony management
      decisions. Further, definition of the MHC diversity of the population satisfies
      one of the prerequisites to MHC association studies and detailed immunological
      investigations in this outbred non-human primate species.

PMID- 21881953
TI  - Dengue virus-specific CD4+ and CD8+ T lymphocytes target NS1, NS3 and NS5 in
      infected Indian rhesus macaques.
AB  - Every year, Dengue virus (DENV) infects approximately 100 million people. There
      are currently several vaccines undergoing clinical studies, but most target the
      induction of neutralizing antibodies. Unfortunately, DENV infection can be
      enhanced by subneutralizing levels of antibodies that bind virions and deliver
      them to cells of the myeloid lineage, thereby increasing viral replication
      (termed antibody-dependent enhancement [ADE]). T lymphocyte-based vaccines may
      offer an alternative that avoids ADE. The goal of our study was to describe the
      cellular immune response generated after primary DENV infection in Indian rhesus
      macaques. We infected eight rhesus macaques with 105 plaque-forming units (PFU)
      of DENV serotype 2 (DENV2) New Guinea C (NGC) strain, and monitored viral load
      and the cellular immune response to the virus. Viral replication peaked at day 4
      post-infection and was resolved by day 10. DENV-specific CD4+ and CD8+ T
      lymphocytes targeted nonstructural (NS) 1, NS3 and NS5 proteins after resolution
      of peak viremia. DENV-specific CD4+ cells expressed interferon-gamma (IFN-gamma)
      along with tumor necrosis factor-alpha (TNF-alpha), interleukin-2 (IL-2), and
      macrophage inflammatory protein-1 beta (MIP-1beta). In comparison, DENV-specific
      CD8+ cells expressed IFN-gamma in addition to MIP-1beta and TNF-alpha and were
      positive for the degranulation marker CD107a. Interestingly, a fraction of the
      DENV-specific CD4+ cells also stained for CD107a, suggesting that they might be
      cytotoxic. Our results provide a more complete understanding of the cellular
      immune response during DENV infection in rhesus macaques and contribute to the
      development of rhesus macaques as an animal model for DENV vaccine and
      pathogenicity studies.

PMID- 21881954
TI  - New urea biosensor based on urease enzyme obtained from Helycobacter pylori.
AB  - The urease enzyme of Helicobacter pylori was isolated from biopsy sample obtained
      from antrum big curvature cell extracts. A new urea biosensor was prepared by
      immobilizing urease enzyme isolated from Helicobacter pylori on
      poly(vinylchloride) (PVC) ammonium membrane electrode by using nonactine as an
      ammonium ionophore. The effect of pH, buffer concentration, and temperature for
      the biosensor prepared with urease from H. pylori were obtained as 6.0, 5 mM, and
      25  degrees C, respectively. We also investigated urease concentration, stirring
      rate, and enzyme immobilization procedures in response to urea of the enzyme
      electrode. The linear working range of the biosensor extends from 1 * 10(-5) to 1
      * 10(-2) M and they showed an apparent Nernstian response within this range. Urea
      enzyme electrodes prepared with urease enzymes obtained from H. pylori and Jack
      bean based on PVC membrane ammonium-selective electrode showed very good
      analytical parameters: high sensitivity, dynamic stability over 2 months with
      less decrease of sensitivity, response time 1-2 min. The analytical
      characteristics were investigated and were compared those of the urea biosensor
      prepared with urease enzyme isolated from Jack bean prepared at the same
      conditions. It was observed that rapid determinations of human serum urea amounts
      were also made possible with both biosensors.

PMID- 21881955
TI  - Variation in the internalization of differently sized nanoparticles induces
      different DNA-damaging effects on a macrophage cell line.
AB  - Although researchers have expended considerable effort on studying the
      cytotoxicity of nanomaterials, it is possible that there has been insufficient
      attention paid to their genotoxic potential. Here, we describe a test model that
      we have developed to evaluate the DNA-damaging effects of negatively charged
      nanoparticles of different sizes. We compared the DNA damaging effect induced by
      nanoparticles of various sizes and found that the effect is closely associated
      with the internalization pattern of the particles. Macrophage cell line RAW 264.7
      cells were incubated with carboxylated polystyrene beads (COOH-PBs) ranging in
      size from 30 to 500 nm. Size-dependent DNA damage was detected, and the lesion
      induced by two carboxylated fullerene particles confirmed this observation.
      Confocal microscopy revealed that the entry pathways of these COOH-PBs shifted
      from direct penetration to endocytosis with increasing particle size, followed by
      changes in subcellular localization. Subsequent deposition of 30-nm COOH-PBs in
      the cytosol led to a reduction of Zn2+ and Mg2+ content in the nucleus and an
      increased p53 level in the whole cell rather than in nucleus, while localization
      of 50- and 100-nm COOH-PBs in acidic vesicles induced p53 accumulation in both
      types of extracts. Based on these results, we assume that the damage resulted
      from a disruption of the balance between DNA damage and repair.

PMID- 21881956
TI  - Control of an Acinetobacter [corrected] baumannii outbreak in a neonatal ICU
      without suspension of service: a devastating outbreak in Diyarbakir, Turkey.
AB  - BACKGROUND: A nosocomial outbreak of Acinetobacter baumannii bloodstream
      infections (Ab-BSI) was identified in Diyarbakir Children's Hospital's
      (Diyarbakir, Turkey) 60-bed Neonatal Intensive Care Unit (NICU) in 2006 and 2007.
      METHODS: The investigation and control of the outbreak were based on case-control
      and epidemiological studies as well as multifaceted interventions. Sixty-four
      neonates (case patients) with Ab-BSI and 128 neonates (control patients) free of
      Ab-BSI, who had been hospitalized at the unit during the outbreak period, were
      included in the study. Case and control patients were compared for possible
      predisposing factors (e.g., gender, length of NICU stay, antibiotic use,
      intubation, etc.). An intervention program (cohorting, education, reinforcing
      hand hygiene, antibiotic restriction, improving processes of patient care,
      environmental cleaning, and barrier isolation) was implemented to control the
      outbreak. Surveillance cultures were collected from all possible sources, and the
      epidemiological investigation was supplemented by a pulsed field gel
      electrophoresis (PFGE) study. RESULTS: Fifty-three neonates (82.8%) died in the
      case group and 51 (39.8%) in the control group (P < 0.001). The duration of stay
      at the NICU [odds ratio (OR) 1.15; 95% confidence interval (CI) 1.07-1.23; P <
      0.001] and re-intubation (OR 38.62; CI 12.66-117.87; P < 0.001) were found to be
      significant risk factors for Ab-BSI. Surveillance cultures showed a heavy
      contamination in the NICU, and the outbreak ended after a series multifaceted
      interventions. All A. baumannii isolates, both from the cases and environmental
      samples, had an identical PFGE fingerprint pattern. CONCLUSION: The control of Ab
      BSI requires a multifaceted intervention program and complex efforts and
      implementations, especially if the ICU does not implement any suspension of care
      provision.

PMID- 21881957
TI  - Risk factors associated with disease progression and mortality in chronic kidney
      disease of uncertain etiology: a cohort study in Medawachchiya, Sri Lanka.
AB  - BACKGROUND: The alarming rise in the prevalence of chronic kidney disease of
      uncertain etiology (CKDu) among the low socioeconomic farming community in the
      North Central Province of Sri Lanka has been recognized as an emerging public
      health issue in the country. METHODS: This study sought to determine the possible
      factors associated with the progression and mortality of CKDu. The study utilized
      a single-center cohort registered in 2003 and followed up until 2009 in a
      regional clinic in the endemic region, and used a Cox proportional hazards model.
      RESULTS: We repeatedly found an association between disease progression and
      hypertension. Men were at higher risk of CKDu than women. A significant
      proportion of the patients in this cohort were underweight, which emphasized the
      need for future studies on the nutritional status of these patients. CONCLUSIONS:
      Compared with findings in western countries and other regions of Asia, we
      identified hypertension as a major risk factor for progression of CKDu in this
      cohort.

PMID- 21881958
TI  - Age related variation in male-male relationships in wild spider monkeys (Ateles
      geoffroyi yucatanensis).
AB  - In social organizations characterized by male philopatry, social relationships
      between males are argued to be the strongest. Little is known about the social
      relationships of philopatric male spider monkeys. To address this limitation, we
      investigated social relationships among individually recognized wild adult male
      spider monkeys from two well-habituated communities in the Yucatan Peninsula,
      Mexico, focusing on affiliative behaviors important in regulating male social
      relationships, including grooming, embracing, arm-wrapping, and grappling. We
      examined whether behaviors were reciprocated between male partners and whether
      age was a factor in how the behaviors were distributed or reciprocated, by
      examining differences between younger adult males (<10 years) and older adult
      males (>=14 years). Although we found evidence that affiliative behaviors were
      overall reciprocated between spider monkey adult males, there were pronounced
      differences in the interactions depending on their relative age. Reciprocation in
      grooming and embraces between same-age males suggests their relationships are
      valuable to both partners. Among different-age dyads, younger males gave more
      embraces than they received, were the initiators of grappling and arm-wrapped
      more often than with same-age males, suggesting relationships between younger and
      older males are more risky. This confirms that younger males are attracted to
      older males, probably because they value relationships with older males more than
      the reverse, but they are also at risk.

PMID- 21881959
TI  - Intergroup variation in stable isotope ratios reflects anthropogenic impact on
      the Barbary macaques (Macaca sylvanus) of Gibraltar.
AB  - Interactions with humans impact many aspects of behavior and ecology in nonhuman
      primates. Because of the complexities of the human-nonhuman primate interface,
      methods are needed to quantify the effects of anthropogenic interactions,
      including their intensity and differential impacts between nonhuman primate
      groups. Stable isotopes can be used to quickly and economically assess intergroup
      dietary variation, and provide a framework for the development of specific
      hypotheses about anthropogenic impact. This study uses stable carbon and nitrogen
      isotope analysis to examine intraspecific variation in diet between five groups
      of Barbary macaques, Macaca sylvanus, in the Upper Rock Nature Reserve,
      Gibraltar. Analysis of hair from 135 macaques showed significant differences in
      delta(13)C and delta(15)N values between a group with minimal tourist contact and
      groups that were main tourist attractions. Because we observed no overt
      physiological or substantial behavioral differences between the groups, feeding
      ecology is the most likely cause of any differences in stable isotope ratios.
      Haphazard provisioning by tourists and Gibraltarians is a likely source of
      dietary variation between groups. Stable isotope analysis and observational data
      facilitate a deeper understanding of the feeding ecology of the Barbary macaques
      relevant to the role of an anthropogenic ecology for the species.

PMID- 21881960
TI  - Imaging exocytosis of ATP-containing vesicles with TIRF microscopy in lung
      epithelial A549 cells.
AB  - Nucleotide release constitutes the first step of the purinergic signaling
      cascade, but its underlying mechanisms remain incompletely understood. In
      alveolar A549 cells much of the experimental data is consistent with Ca(2+)
      regulated vesicular exocytosis, but definitive evidence for such a release
      mechanism is missing, and alternative pathways have been proposed. In this study,
      we examined ATP secretion from A549 cells by total internal reflection
      fluorescence microscopy to directly visualize ATP-loaded vesicles and their
      fusion with the plasma membrane. A549 cells were labeled with quinacrine or
      Bodipy-ATP, fluorescent markers of intracellular ATP storage sites, and time
      lapse imaging of vesicles present in the evanescent field was undertaken. Under
      basal conditions, individual vesicles showed occasional quasi-instantaneous loss
      of fluorescence, as expected from spontaneous vesicle fusion with the plasma
      membrane and dispersal of its fluorescent cargo. Hypo-osmotic stress stimulation
      (osmolality reduction from 316 to 160 mOsm) resulted in a transient, several-fold
      increment of exocytotic event frequency. Lowering the temperature from 37 degrees
      C to 20 degrees C dramatically diminished the fraction of vesicles that underwent
      exocytosis during the 2-min stimulation, from ~40% to <=1%, respectively.
      Parallel ATP efflux experiments with luciferase bioluminescence assay revealed
      that pharmacological interference with vesicular transport (brefeldin, monensin),
      or disruption of the cytoskeleton (nocodazole, cytochalasin), significantly
      suppressed ATP release (by up to ~80%), whereas it was completely blocked by N
      ethylmaleimide. Collectively, our data demonstrate that regulated exocytosis of
      ATP-loaded vesicles likely constitutes a major pathway of hypotonic stress
      induced ATP secretion from A549 cells.

PMID- 21881961
TI  - Effects of 3 weeks GMP oral administration on glutamatergic parameters in mice
      neocortex.
AB  - Overstimulation of the glutamatergic system (excitotoxicity) is involved in
      various acute and chronic brain diseases. Several studies support the hypothesis
      that guanosine-5'-monophosphate (GMP) can modulate glutamatergic
      neurotransmission. The aim of this study was to evaluate the effects of
      chronically administered GMP on brain cortical glutamatergic parameters in mice.
      Additionally, we investigated the neuroprotective potential of the GMP treatment
      submitting cortical brain slices to oxygen and glucose deprivation (OGD).
      Moreover, measurements of the cerebrospinal fluid (CSF) purine levels were
      performed after the treatment. Mice received an oral administration of saline or
      GMP during 3 weeks. GMP significantly decreases the cortical brain glutamate
      binding and uptake. Accordingly, GMP reduced the immunocontent of the glutamate
      receptors subunits, NR2A/B and GluR1 (NMDA and AMPA receptors, respectively) and
      glutamate transporters EAAC1 and GLT1. GMP treatment significantly reduced the
      immunocontent of PSD-95 while did not affect the content of Snap 25, GLAST and
      GFAP. Moreover, GMP treatment increased the resistance of neocortex to OGD
      insult. The chronic GMP administration increased the CSF levels of GMP and its
      metabolites. Altogether, these findings suggest a potential modulatory role of
      GMP on neocortex glutamatergic system by promoting functional and plastic changes
      associated to more resistance of mice neocortex against an in vitro
      excitotoxicity event.

PMID- 21881963
TI  - Multivariate, longitudinal analysis of the impact of changes in office work
      environments on surface electromyography measures.
AB  - PURPOSE: To detect impacts of changes in work environment and worker-equipment
      interface variables upon surface electromyography (EMG) measures using
      multivariate, longitudinal analysis. METHODS: For 33 office workers, yearly
      measurements (1999-2001) were taken during normal work. Independent variables
      were related to work environment (expert-observed equipment dimensions, work
      organization on questionnaire) and interface (expert-observed postures, self
      reported workstation-equipment relative fit i.e. inside or outside guidelines
      informed location, and 30 min video-based task analysis). Internal mechanical
      exposure (EMG) was recorded bilaterally from extensor carpi radialis brevis
      (ECRB) and upper trapezius sites, each side, also for 30 min. Dependent variables
      were amplitude probability distribution functions (APDF 50 and 90%) and gaptime
      for entire record EMG (over all tasks) and task-specific EMG (for four separate
      tasks). Multivariate mixed models used independent variables to predict EMG
      measures (4 muscle sites * (1 entire record + 4 task specific) = 20 models
      total). RESULTS: Among EMG measures, 9/16 means and 2/16 variances were
      significantly different across years (p < 0.1). Environment and interface
      variables explained part of the variation in EMG measures in 13/20 models. The
      most consistent predictors included: (1) increased monitor distance predicted
      reduced APDFs and increased gaptimes; (2) wrist extension <20 degrees  predicted
      decreases in left ECRB APDFs; (3) keyboard location within guidelines predicted
      improvements in all right ECRB EMG measures during keyboarding; and (4) longer
      task duration predicted higher APDFs and lower gaptimes. CONCLUSION: Longitudinal
      analysis with multivariate models can detect the impacts of changes in
      environment and interface exposures on EMG measures among office workers.

PMID- 21881965
TI  - Repetitive behavior profiles: Consistency across autism spectrum disorder cohorts
      and divergence from Prader-Willi syndrome.
AB  - Restricted and repetitive behavior (RRB) is a group of heterogeneous maladaptive
      behaviors. RRB is one of the key diagnostic features of autism spectrum disorders
      (ASDs) and also commonly observed in Prader-Willi syndrome (PWS). In this study,
      we assessed RRB using the Repetitive Behavior Scale-Revised (RBS-R) in two ASD
      samples (University of Illinois at Chicago [UIC] and University of Florida [UF])
      and one PWS sample. We compared the RBS-R item endorsements across three ASD
      cohorts (UIC, UF and an ASD sample from Lam, The Repetitive Behavior Scale
      Revised: independent validation and the effect of subject variables, PhD thesis,
      2004), and a PWS sample. We also compared the mean RBS-R subscale/sum scores
      across the UIC, UF and PWS samples; across the combined ASD (UIC + UF), PWS
      deletion and PWS-disomy groups; and across the combined ASD sample, PWS subgroup
      with a Social Communication Questionnaire (SCQ) score >=15, and PWS subgroup with
      a SCQ score <15. Despite the highly heterogeneous nature, the three ASD samples
      (UIC, UF and Lam's) showed a similar pattern of the RBS-R endorsements, and the
      mean RBS-R scores were not different between the UIC and UF samples. However,
      higher RRB was noted in the ASD sample compared with the PWS sample, as well as
      in the PWS subgroup with a SCQ score >=15 compared with the PWS subgroup with a
      SCQ score <15. Study limitations include a small sample size, a wide age range of
      our participants, and not controlling for potential covariates. A future
      replication study using a larger sample and further investigation into the
      genetic bases of overlapping ASD and RRB phenomenology are needed, given the
      higher RRB in the PWS subgroup with a SCQ score >=15.

PMID- 21881964
TI  - A novel clinical entity, IgG4-related disease (IgG4RD): general concept and
      details.
AB  - IgG4-related disease (IgG4RD) is a novel clinical disease entity characterized by
      elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4
      positive plasma cells. IgG4RD may be present in a certain proportion of patients
      with a wide variety of diseases, including Mikulicz's disease, autoimmune
      pancreatitis, hypophysitis, Riedel thyroiditis, interstitial pneumonitis,
      interstitial nephritis, prostatitis, lymphadenopathy, retroperitoneal fibrosis,
      inflammatory aortic aneurysm, and inflammatory pseudotumor. Although IgG4RD forms
      a distinct, clinically independent disease category and is attracting strong
      attention as a new clinical entity, many questions and problems still remain to
      be elucidated, including its pathogenesis, the establishment of diagnostic
      criteria, and the role of IgG4. Here we describe the concept of IgG4RD and up-to
      date information on this emerging disease entity.

PMID- 21881966
TI  - Non-alcoholic fatty liver induces insulin resistance and metabolic disorders with
      development of brain damage and dysfunction.
AB  - In the present study we investigated the effect of the non-alcoholic fatty liver
      disease (NAFLD) on the alterations in the activity of neurotransmitters
      catabolizing enzymes and energy catabolising enzymes, prooxidants, endogenous
      antioxidants and proinflammatory cytokines in brain tissue of NAFLD rats. Rats
      were intraperitonealy injected with CCl4 solution at a dose of (0.021 mole/Kg, 20
      MUL, body weight) three times weekly for four weeks. Acetylcholine esterase
      (AChE), monoamine oxidase (MAO), prooxidant/ antioxidants status, ATPase, lipid
      profile and glucose level were estimated spectrophotometrically while
      inflammatory markers; interleukin 6 and tumor necrosis factor alpha (IL6 and TNF
      alpha) and insulin were assessed by ELISA technique. Our results showed that the
      induced NAFLD and insulin resistance (IR) were accompanied with hyperglycemia and
      hyperlipidemia and lowered brain glucose level with elevated ATPase activity,
      prooxidant status (TBARS level, xanthine oxidase and cytochrome 2E1 activities),
      and inflammatory markers. Through the induction period AChE activity was
      significantly increased compared to control in blood, liver and brain tissues.
      Also, MAO activity was significantly increased in both brain and liver tissue but
      decreased in serum compared with control. These biochemical data were supported
      with pathophysiological analysis that showed severe neurodegeneration, pyknosis
      acuolations and cavitations. These observations warrant the reassessment of the
      conventional concept that the NAFLD with IR progression may induce disturbances
      in activities of neurotransmitters catabolising enzymes and energy production
      accompanied with oxidative stress and metabolic disorders, acting as relative
      risk factors for brain dysfunction and damage with the development of age
      associated neurodegenerative diseases such as Alzheimer's disease.

PMID- 21881967
TI  - Forearm bone mineral density changes during postpartum and the effects of
      breastfeeding, amenorrhea, body mass index and contraceptive use.
AB  - Prospective cohort study performed to evaluate bone mineral density (BMD) changes
      up to 12 months postpartum of healthy women and its association with
      breastfeeding, contraceptive methods, amenorrhea, and body mass index (BMI).
      There is a trend in bone loss during the first 6 months with posterior recovery,
      with evidence of a protective effect of hormonal contraception. INTRODUCTION:
      This study was conducted to evaluate bone mineral density (BMD) changes during
      postpartum period among healthy women and its association with breastfeeding, use
      of contraceptive methods, amenorrhea and body mass index (BMI). METHODS: A
      prospective cohort study including 100 healthy women. Distal BMD was measured 7
      10 days, 3, 6, and 12 months postpartum at the nondominant forearm using dual
      energy X-ray absorptiometry. Data about breastfeeding duration, amenorrhea,
      contraceptive use and BMI were collected. RESULTS: Seventy-eight women had a
      complete set of BMD measurements. The mean duration of exclusive breastfeeding
      was 125.9 (+/-66.6) days, with a median total lactation period of 263.5 days. The
      mean duration of amenorrhea was 164.2 (+/-119.2) days. BMD measurements showed a
      significant decrease in the distal radius, however with no significance in the
      ultradistal radius. When considering only the nonhormonal contraceptive users,
      the difference at 12 months was significant. Multivariate analysis of variance
      showed that both BMI and contraceptive use were significantly correlated with
      BMD. Multiple linear regression analysis showed significant correlation of distal
      radius with baseline BMD at the same site, pregestational BMI, age, years of
      schooling and difference in BMI. For ultradistal radius, there was a significant
      direct correlation with its baseline BMD and pregestational BMI. CONCLUSIONS:
      There was a trend in bone loss during the first 6 months postpartum with
      posterior recovery. Also, hormonal contraceptive methods provided protection of
      bone loss. However, the long duration of breastfeeding and the follow-up were not
      sufficient to draw definitive conclusions on postweaning BMD conditions.

PMID- 21881968
TI  - Geometric indices of hip bone strength in obese, overweight, and normal-weight
      adolescent boys.
AB  - The aim of this study was to compare hip bone strength indices in obese,
      overweight, and normal-weight adolescent boys using hip structure analysis. After
      adjusting for weight, obese boys displayed lower intertrochanteric cross
      sectional moment of inertia and femoral shaft cross-sectional moment of inertia
      and section modulus in comparison to normal-weight and overweight boys. This
      study suggests that in obese adolescent boys, femoral shaft bending strength is
      not adapted to the increased body weight. INTRODUCTION: The influence of being
      obese or overweight on bone strength in adolescents remains controversial. The
      main aim of this study was to compare hip bone strength indices in obese,
      overweight, and normal-weight adolescent boys using hip structure analysis. The
      second aim of this study was to explore the influence of lean mass and fat mass
      on hip bone strength indices in the same population. METHODS: This study included
      70 adolescent boys (25 obese, 25 normal weight, and 20 overweight). The three
      groups (obese, overweight, and normal weight) were matched for maturity (Tanner
      stage) and age. Body composition and bone mineral density (BMD) were assessed by
      dual-energy X-ray absorptiometry (DXA). To evaluate hip bone strength, DXA scans
      were analyzed at the femoral neck (FN), the intertochanteric (IT), and the
      femoral shaft (FS) by the Hip Structure Analysis (HSA) program. Cross-sectional
      area (CSA), an index of axial compression strength, section modulus (Z), an index
      of bending strength, and cross-sectional moment of inertia (CSMI), an index of
      structural rigidity were measured from bone mass profiles. RESULTS: Body weight,
      lean mass, fat mass and BMI were significantly higher in obese and overweight
      boys in comparison to normal-weight boys (P < 0.05). Total hip (TH) BMD and
      femoral neck (FN) BMD were significantly higher in obese and overweight boys in
      comparison to normal-weight boys (P < 0.05). After adjusting for age or
      maturation index, obese and overweight boys displayed significantly higher TH and
      FN BMD, CSA, CSMI, and Z of the three sites (FN, IT, and FS) in comparison to
      normal-weight boys (P < 0.05). However, after adjusting for weight, obese boys
      displayed significantly lower IT CSMI and FS CSMI and Z in comparison to normal
      weight and overweight boys (P < 0.05). CONCLUSIONS: This study suggests that in
      obese adolescent boys, intertrochanteric structural rigidity and femoral shaft
      structural rigidity and bending strength are not adapted to the increased body
      weight.

PMID- 21881971
TI  - Intravenous injection of endogenous microbial components abrogates DSS-induced
      colitis.
AB  - BACKGROUND: The etiology of inflammatory bowel diseases (IBD) is largely unknown,
      but appears to be perpetuated by uncontrolled responses to antigenic components
      of the endogenous flora. Tolerance to antigenic stimulation can be achieved by
      exposure to a given antigen in high amounts (high dose tolerance). Colitis
      induced by feeding of Dextran Sodium Sulfate (DSS) is an often-used animal model
      mimicking clinical and histological features of human IBD. AIMS: We investigated
      whether treatment with high doses of endogenous bacterial components can affect
      the response to these antigenic components and thus impact the course of the
      inflammatory response induced by DSS. METHODS: 129/SvEv mice were injected
      intravenously in the tail vein with lysates prepared from fecal material of
      conventionally-raised mice. Control mice received a solution of bacterial antigen
      free lysates prepared from fecal material of germ-free mice. Seven days later,
      colitis was induced in these mice by introducing DSS (3.5%) in the drinking water
      for 5 days. Onset and course of the inflammatory response was monitored by
      assessment of weight loss. Mice were sacrificed at day 7 post colitis induction
      and tested for histopathologic injury, intestinal cytokine release, and systemic
      response to bacterial antigens. RESULTS: Intravenous injection with fecal lysates
      reduced intestinal and antigen-stimulated systemic pro-inflammatory cytokine
      release and prevented DSS-induced weight loss and intestinal injury. CONCLUSION:
      Pretreatment with high amount of endogenous bacterial components has a profound
      tolerogenic effect on the systemic and mucosal immune responses resulting in
      reduced intestinal inflammation and abrogates colitis-induced weight loss.

PMID- 21881969
TI  - Runx2 promotes both osteoblastogenesis and novel osteoclastogenic signals in ST2
      mesenchymal progenitor cells.
AB  - We profiled the global gene expression of a bone marrow-derived mesenchymal
      pluripotent cell line in response to Runx2 expression. Besides osteoblast
      differentiation, Runx2 promoted the osteoclastogenesis of co-cultured
      splenocytes. This was attributable to the upregulation of many novel
      osteoclastogenic genes and the downregulation of anti-osteoclastogenic genes.
      INTRODUCTION: In addition to being a master regulator for osteoblast
      differentiation, Runx2 controls osteoblast-driven osteoclastogenesis. Previous
      studies profiling gene expression during osteoblast differentiation had limited
      focus on Runx2 or paid little attention to its role in mediating osteoblast
      driven osteoclastogenesis. METHODS: ST2/Rx2(dox), a bone marrow-derived
      mesenchymal pluripotent cell line that expresses Runx2 in response to Doxycycline
      (Dox), was used to profile Runx2-induced gene expression changes. Runx2-induced
      osteoblast differentiation was assessed based on alkaline phosphatase staining
      and expression of classical marker genes. Osteoclastogenic potential was
      evaluated by TRAP staining of osteoclasts that differentiated from primary murine
      splenocytes co-cultured with the ST2/Rx2(dox) cells. The BeadChipTM platform
      (Illumina) was used to interrogate genome-wide expression changes in ST2/Rx2(dox)
      cultures after treatment with Dox or vehicle for 24 or 48 h. Expression of
      selected genes was also measured by RT-qPCR. RESULTS: Dox-mediated Runx2
      induction in ST2 cells stimulated their own differentiation along the osteoblast
      lineage and the differentiation of co-cultured splenocytes into osteoclasts. The
      latter was attributable to the stimulation of osteoclastogenic genes such as
      Sema7a, Ltc4s, Efnb1, Apcdd1, and Tnc as well as the inhibition of anti
      osteoclastogenic genes such as Tnfrsf11b (OPG), Sema3a, Slco2b1, Ogn, Clec2d
      (Ocil), Il1rn, and Rspo2. CONCLUSION: Direct control of osteoblast
      differentiation and concomitant indirect control of osteoclast differentiation,
      both through the activity of Runx2 in pre-osteoblasts, constitute a novel
      mechanism of coordination with a potential crucial role in coupling bone
      formation and resorption.

PMID- 21881973
TI  - High dose lamivudine in HBV-related cirrhotic patients with unsatisfactory
      response after adefovir add-on.
AB  - BACKGROUND: Before tenofovir approval for chronic hepatitis B therapy, the
      clinical management of patients with suboptimal response or virological
      breakthrough during combination treatment with lamivudine and adefovir dipivoxil
      was a difficult clinical challenge. AIMS: In order to improve virologic response
      and reduce the risk of decompensation, we evaluate the efficacy of a high dose of
      lamivudine on chronic HBV patients who have previously presented an
      unsatisfactory response during treatment with lamivudine 100mg/day and adefovir
      10mg/day. METHODS: Six patients with HBV-related liver cirrhosis were
      prospectively enrolled. All were HBeAg-negative and presented a suboptimal
      response or virological breakthrough after "adefovir add-on" because of
      development of clinical breakthrough during Lamivudine treatment. Lamivudine dose
      was increased to 200 or 300 mg, depending on viral load. After 12 months of
      follow-up, virological and biochemical response were evaluated. RESULTS: After 12
      months of high-dose lamivudine, all patients (6/6, 100%) achieved a significant
      decrease of serum HBV DNA (mean reduction 2,62 +/- 1,15 Log10 UI/ml, P = 0.03)
      and normalized ALT. In three patients (3/6, 50%), HBV DNA became undetectable
      within 6 months. No patient developed liver decompensation and no significant
      changes occurred in serum creatinine, serum and urinary electrolytes. No adverse
      events were registered. CONCLUSIONS: In our experience, rescue strategy with high
      dose lamivudine inhibited viral replication leading to undetectability of serum
      HBVDNA. This rescue treatment presented a good safety profile, without adverse
      events during the study period. Customized increase of nucleos(t)ide analogues
      dose in difficult-to-treat patients may be a proficient approach in challenging
      clinical setting.

PMID- 21881972
TI  - Clinicopathologic features and treatment outcomes in Cronkhite-Canada syndrome:
      support for autoimmunity.
AB  - BACKGROUND AND AIMS: Cronkhite-Canada syndrome (CCS) is a noninherited condition,
      associated with high morbidity, and characterized by gastrointestinal
      hamartomatous polyposis, alopecia, onychodystrophy, hyperpigmentation, and
      diarrhea. All features may respond to immunosuppressive therapy, but little is
      known about the etiology. An autoimmune origin has been suggested but not proved.
      From a retrospectively selected cohort, we evaluated clinicopathologic features,
      including immunostaining for IgG4 (an antibody associated with autoimmunity), and
      therapeutic outcomes in a cohort of CCS patients to provide further insights into
      this disease. METHODS: Cases included 14 consecutive CCS patients seen at the
      Mayo Clinic on whom tissue and follow-up were available. All histology was
      reviewed by an expert gastrointestinal pathologist. Immunostaining for IgG4 was
      performed on 42 polyps from CCS cases and on control tissues, including 46
      histologically similar hamartomas [from juvenile polyposis syndrome (JPS)] and 20
      normal mucosae (six stomach, three small bowel, and 11 colon). Clinical features
      and treatment outcomes were descriptive. RESULTS: All CCS cases had both upper
      and lower gastrointestinal polyps; most had typical dermatologic features of
      alopecia, hyperpigmentation, and onychodystrophy; and most had evidence of
      protein-losing enteropathy. Ten patients (71%) had adenomatous polyps and 2 (14%)
      had colorectal cancer. IgG4 immunostaining was positive (>5 cells/HPF) in 52% of
      CCS polyps compared to 12% of JPS polyps (P = 0.001); IgG4 staining was negative
      in all other control tissues. Of 11 CCS patients treated with oral
      corticosteroids, 91% achieved remission. Relapse was common with steroid
      tapering. Five patients who initially responded to corticosteroids were
      maintained in remission on azathioprine (2 mg/kg/day) with no relapse after a
      median of 4.5 years. CONCLUSIONS: Immunostaining for the autoimmune-related IgG4
      antibody is significantly increased in CCS polyps compared to disease and normal
      control tissues. Furthermore, immunosuppression by corticosteroids or long-term
      azathioprine may eradicate or lessen manifestations of CCS. These histologic
      findings and treatment responses are consistent with an autoimmune mechanism
      underlying CCS.

PMID- 21881974
TI  - Impact of calcineurin inhibitors on hepatitis C recurrence after liver
      transplantation.
AB  - BACKGROUND AND AIMS: The aim of this retrospective study is to assess the impact
      of calcineurin inhibitors on hepatitis C virus recurrence following liver
      transplantation. METHODS: A total of 396 patients underwent liver transplantation
      for hepatitis C virus-induced liver disease between 1991 and 2005 at a single
      center. We examined the pre- and post-operative characteristics of patients who
      received either cyclosporine (n = 126) or tacrolimus (n = 270) as maintenance
      immunosuppression. In addition, we compared the postoperative course, including
      patient, graft and hepatitis C virus recurrence-free survival between the two
      groups. RESULTS: There were no significant differences between the two groups in
      either post-operative hepatitis C virus-ribonucleic acid or histological fibrosis
      score (performed within 6 months after transplant per protocol). The graft and
      patient survivals did not differ between the two groups (logrank p = 0.34 and
      0.15, respectively). Histologic hepatitis C virus recurrence-free survival,
      however, was significantly higher in the cyclosporine group than in the
      tacrolimus group (55.4 vs. 30.8% at 1 year, 18.6 vs. 10.3% at 3 years, 16.7 vs.
      8.1% at 5 years, p < 0.001). CONCLUSIONS: Patients transplanted for hepatitis C
      virus and treated with cyclosporine versus tacrolimus may have a higher
      recurrence-free survival.

PMID- 21881975
TI  - Oral nitrate reductase activity and erosive gastro-esophageal reflux disease: a
      nitrate hypothesis for GERD pathogenesis.
AB  - BACKGROUND: Despite the rich literature on GERD, its cause and reason for
      increased prevalence remain obscure. Currently accepted mechanisms leave many
      questions unanswered. Nitrite chemistry at the GEJ is well described for
      carcinogenesis. Recent epidemiological and animal data have linked nitrates to
      GERD. "Nitrate reductase" of oral bacteria converts nitrates to nitrites. We
      hypothesized that nitrate reductase activity is higher in patients with erosive
      GERD, delivering more nitrite at the gastroesophageal-junction for a given
      nitrate intake. AIM: To compare oral nitrate reductase activity of erosive GERD
      patients with controls. METHODS: Patients with erosive GERD and controls without
      GERD were enrolled. After overnight fasting, nitrite of oral cavity contents was
      measured at 1-min intervals for 3 min while incubating a 10-mg nitrate-N/L
      solution in the mouth. Nitrate reductase activity was calculated and compared
      between groups. RESULTS: Eleven cases (ten males, mean age: 42.6 +/- 11.7 year)
      and ten controls (eight males, mean age: 37.6 +/- 9.2 year) were enrolled. Mean
      nitrate reductase activity was 3.23 +/- 0.99 vs. 2.30 +/- 0.83 "MUg nitrite-N
      formed/person/minute" in cases and controls, respectively (p = 0.03).
      CONCLUSIONS: Oral nitrate reductase activity in erosive GERD patients is higher
      than controls. Therefore, any dietary nitrate load generates more nitrite in
      these patients. This excess nitrite at the gastroesophageal junction, may
      potentially contribute to the development of GERD. This is the first report
      linking oral nitrite production to erosive GERD in man. We suggest that a
      "nitrate hypothesis" may answer yet unanswered questions about GERD pathogenesis.
      If confirmed, it may change our understanding of mechanisms of GERD and provide
      novel therapeutic targets.

PMID- 21881976
TI  - BMP signals and the transcriptional repressor BLIMP1 during germline segregation
      in the mammalian embryo.
AB  - Molecular factors and tissue compartments involved in the foundation of the
      mammalian germline have been mainly described in the mouse so far. To find
      mechanisms applicable to mammals in general, we analyzed temporal and spatial
      expression patterns of the transcriptional repressor BLIMP1 (also known as PRDM1)
      and the signaling molecules BMP2 and BMP4 in perigastrulation and early
      neurulation embryos of the rabbit using whole-mount in situ hybridization and
      high-resolution light microscopy. Both BMP2 and BMP4 are expressed in annular
      domains at the boundary of the embryonic disc, which--in contrast to the
      situation in the mouse--partly belong to intraembryonic tissues. While BMP2
      expression begins at (pregastrulation) stage 1 in the hypoblast, BMP4 expression
      commences--distinctly delayed compared to the mouse--diffusely at
      (pregastrulation) stage 2; from stage 3 onwards, BMP4 is expressed peripherally
      in hypoblast and epiblast and in the mesoderm at the posterior pole of the
      embryonic disc. BLIMP1 expression begins throughout the hypoblast at stage 1 and
      emerges in single primordial germ cell (PGC) precursors in the posterior epiblast
      at stage 2 and then in single mesoderm cells at positions identical to those
      identified by PGC-specific antibodies. These expression patterns suggest that
      function and chronology of factors involved in germline segregation are similar
      in mouse and rabbit, but higher temporal and spatial resolution offered by the
      rabbit demonstrates a variable role of bone morphogenetic proteins and makes
      "blimping" a candidate case for lateral inhibition without the need for an
      allantoic germ cell niche.

PMID- 21881979
TI  - Evaluation of cartilage degradation in arthritis using T1rho magnetic resonance
      imaging mapping.
AB  - T1rho magnetic resonance imaging (MRI) can be used to map proteoglycan (PG) loss
      in cartilage. Here, we used T1rho MRI to map cartilage degradation in
      osteoarthritis (OA) and rheumatoid arthritis (RA). Tissue samples were obtained
      from five RA patients and 14 OA patients following total knee arthroplasty (TKA).
      Three parameters were measured: First, macroscopic grading of cartilage sample
      tissues was performed on a 5-grade scale (G0: normal, G1: swelling, G2:
      superficial fibrillation, G3: deep fibrillation, G4: subchondral bone exposure).
      Second, semi-quantitative values of PG were assessed by measuring the optical
      density of Safranin-O-stained paraffin sections that had been digitally
      photographed. Third, cartilage was divided into superficial and deep layers and
      the T1rho values were quantified. T1rho values of OA and RA in the superficial
      layers showed significant differences between groups (G0/1 and G0/2 for OA; G0/2
      and G1/2 for RA). In the deep layers, T1rho values of OA and RA also differed
      significantly between groups. In both the superficial and deep layers, there was
      a significant correlation between the mean T1rho values and macroscopic grading
      (P < 0.01 for OA, P < 0.001 for RA). We found a negative correlation between the
      score of Safranin-O staining and T1rho values (r = -0.61 for OA, r = -0.79 for
      RA). In addition, RA subjects had significantly higher T1rho values than OA
      subjects of similar morphologic grade. In conclusion, T1rho MRI is able to detect
      and map the early stages of cartilage degradation in OA and RA. This method is
      reliable and useful for the evaluation of macromolecular changes in arthritic
      cartilage.

PMID- 21881977
TI  - Endothelin-induced changes in blood flow in STZ-diabetic and non-diabetic rats:
      relation to nitric oxide synthase and cyclooxygenase inhibition.
AB  - In this study, using the microsphere method, the hemodynamic response to
      endothelin-1 (ET-1) in healthy and streptozotocin (STZ)-diabetic rats was
      evaluated as well as the influences of inhibition of nitric oxide (NO)-synthase
      using L-NAME (Nomega-nitro-L: -arginine methyl ester) and the cyclooxygenase
      inhibitor indomethacin. Blood flow (Q) was measured in tissues of interest for
      vascular complications in diabetes such as kidney, eye, brain, heart and skeletal
      muscle with the main focus on ophthalmic circulation. Under resting conditions,
      evidence for renal vasoconstriction was found in diabetic animals. In both
      groups, administration of L-NAME reduced Q in all investigated tissues indicating
      a basal NO influence. In the normal rats, ET-1 induced a significant increase in
      blood pressure and intense vasoconstriction in all tissues except in the choroid
      of the eye and in the brain, where it induced an increased Q. In the STZ-diabetic
      rats, effects of ET-1 were less pronounced. Pretreatment with L-NAME, but not the
      cyclooxygenase inhibitor, abolished the ET-1-induced vasodilation in the choroid
      of both groups. Administration of ET A receptor antagonist BQ-123 reduced the ET
      1-induced vasodilation in the choroid only in diabetic animals. In conclusion,
      evidence for altered vascular endothelial response to ET-1 in STZ-diabetic
      animals was found particularly in the ophthalmic circulation. The findings
      suggest differential involvement of receptors in the response to ET-1 in normal
      and STZ-diabetic animals.

PMID- 21881980
TI  - Drug-induced lupus in anti-TNF-alpha therapy and its treatment with rituximab.
AB  - We report three patients with rheumatoid arthritis (RA) who were treated with
      anti-TNF-alpha agents and who developed drug-induced lupus (DIL). Two of them
      received etanercept and the remainder adalimumab. We also present the favorable
      response observed with the withdrawal of the anti-TNF-alpha agents and the
      introduction of rituximab. Through this intervention, we observed a very good
      control of the activity of both DIL and RA without additional adverse reactions.

PMID- 21881978
TI  - Comprehensive assessment of prognostic factors predicting outcome in Chinese
      patients with chronic lymphocytic leukemia treated with fludarabine and
      cyclophosphamide.
AB  - To determine whether prognostic factors remain relevant to chronic lymphocytic
      leukemia (CLL) patients treated with fludarabine and cyclophosphamide (FC), we
      prospectively evaluated 86 Chinese CLL patients who received FC in first-line
      therapy. Twenty-four patients (27.9%) achieved complete remission (CR), and
      overall response rate was 75.6%. With a median follow-up of 41 months, the median
      progression-free survival (PFS) was 36.0 months and median overall survival (OS)
      has not been reached. The strong correlations of lower CR rate with advanced
      Binet stage, unmutated IGHV, cytogenetic abnormalities of del(17p13) or
      del(11q23), and p53 mutations were observed by univariable analyses. Stepwise
      logistic regression identified that unmutated IGHV and p53 abnormality (p53
      deletion or mutation) were associated with a decreased odds of achieving CR. The
      less cycles of treatment, not achieving CR, advanced Binet stage, and p53
      abnormality significantly correlated with a shortened PFS. Furthermore, in a
      multivariate analysis, p53 abnormality and advanced Binet stage were identified
      as being significant risk factors for early relapse. Not achieving CR, advanced
      Binet stage, ZAP-70-positive, and p53 abnormality were the adverse factors in
      determining OS. Only p53 aberration was independently associated with
      significantly shorter OS by a multivariate analysis. These results suggest that
      patients with p53 abnormality should be considered for alternative therapies.

PMID- 21881981
TI  - Behcet disease and celiac disease: to screen or not?

PMID- 21881982
TI  - Fever is not always present in Kawasaki disease.

PMID- 21881983
TI  - Chorea in primary antiphospholipid syndrome is associated with rheumatic fever.
AB  - The aim of the study is to evaluate the frequency of chorea in a cohort of
      primary antiphospholipid syndrome (PAPS) patients and their possible clinical and
      laboratory associations. The records of 88 PAPS patients, fulfilling Sapporo
      criteria, followed up at the rheumatology outpatient clinic, were analyzed in
      order to determine the frequency of chorea. Risk factors for chorea, clinical
      manifestations, associated comorbidities, serologic features and treatment
      strategies were analyzed. Eighty-eight PAPS patients were evaluated. Mean age was
      40.6 +/- 11.1 years, and 91% of them were Caucasian and 91% women. Four (4.5%)
      patients with chorea were identified: 2 of them (50%) had only one chorea episode
      and 2 (50%) had recurrent chorea. All patients had chorea onset before PAPS
      diagnosis. Mean age, gender and ethnical distribution were comparable in groups
      with or without seizures (P > 0.05). Interestingly, the comparison of the 4 PAPS
      patients with chorea with those without this abnormality (n = 84) demonstrated a
      lower BMI [21.1 (18-24.2) vs. 27.5 (17.5-40.9) kg/m(2), P = 0.049] and frequency
      of venous events (0 vs. 63.1%, P = 0.023) in the first group. A higher frequency
      of rheumatic fever (75% vs. 0, P < 0.001) and thrombocytopenia (75 vs. 21.4%, P =
      0.041) was observed in PAPS individuals with chorea. Both groups were alike
      regarding the other clinical APS manifestations, disease duration, risk factors
      for cerebrovascular diseases, use of drugs and antiphospholipid antibodies (P >
      0.05). This study demonstrated that 4.5% of PAPS patients had chorea,
      predominately before PAPS diagnosis, and this neurological abnormality was
      associated with rheumatic fever and thrombocytopenia. These data reinforce the
      need for RF diagnosis in those PAPS patients with chorea.

PMID- 21881984
TI  - Pulmonary tuberculosis and tuberculous arthritis of knee joint associated with
      rheumatoid arthritis treated with anti-tumor necrosis factor (TNF)-alpha
      medication: a case report.
AB  - Tuberculosis infection (TB) is one of the most important problems for the
      rheumatoid arthritis (RA) patients treated with anti-TNF agents. Pulmonary
      tuberculosis is the most common clinic form of the TB in these patients. However,
      tuberculosis arthritis is very rare. We present here a 72-year-old Caucasian
      woman with seropositive RA, treated with etanercept/adalimumab for the last 2
      years, who presented with resistant knee pain and joint effusion. We believe that
      this treatment caused the tuberculosis in this patient, which is the most worried
      complication. Interestingly, tuberculosis was in the knee joint at this time.

PMID- 21881985
TI  - Low level of seroconversion after a novel influenza A/H1N1/2009 vaccination in
      Japanese patients with rheumatoid arthritis in the 2009 season.
AB  - We examined change in the antibody titre against pandemic influenza A/H1N1/2009
      before and after vaccination in Japanese patients with rheumatoid arthritis. This
      observational study was conducted with the participation of five hospitals in
      Japan. A total of 89 patients with rheumatoid arthritis were included in this
      study. The seroprotection and seroresponse rates to vaccination with the pandemic
      influenza A/H1N1/2009 vaccine were analysed. The seroprotection rates prior to
      the vaccination were 5.6% in the Japanese patients with rheumatoid arthritis. The
      seroprotection rates after subcutaneous vaccination were 55.1%. The seroresponse
      rate after subcutaneous vaccination was 50.6% in the patients with rheumatoid
      arthritis. Both the seroprotection and seroresponse rates obtained after the
      vaccination with the pandemic influenza A/H1N1/2009 vaccine were low in Japanese
      patients with rheumatoid arthritis. We should realise that a vaccination against
      this newly emerged influenza virus may protect only half of the Japanese patients
      with rheumatoid arthritis in a real world.

PMID- 21881986
TI  - Lack of antiphospolipid antibodies in long-term cardiac rheumatic fever.

PMID- 21881987
TI  - Sarcoidosis and sacroiliitis, a case report.
AB  - Sarcoidosis is a multisystem disorder of unknown etiology characterized by the
      presence of non-caseating granulomas in the organs affected. Sarcoid arthropathy
      is a rare manifestation, and sacroiliitis is an unusual first manifestation of
      the disorder.

PMID- 21881988
TI  - Injection-site reactions upon Kineret (anakinra) administration: experiences and
      explanations.
AB  - Anakinra (Kineret), a recombinant form of human interleukin-1 (IL-1) receptor
      antagonist, is approved for the treatment of rheumatoid arthritis (RA) in
      combination with methotrexate. Kineret is self-administered by daily subcutaneous
      injections in patients with active RA. The mechanism of action of anakinra is to
      competitively inhibit the local inflammatory effects of IL-1. Kineret is
      generally safe and well tolerated and the only major treatment-related side
      effects that appear are skin reactions at the injection site. Due to the
      relatively short half-life of anakinra, daily injection of the drug is required.
      This, in combination with the comparably high rates of injection-site reactions
      (ISRs) associated with the drug, can become a problem for the patient. The
      present review summarises published data concerning ISRs associated with Kineret
      and provides some explanations as to their cause. The objective is also to
      present some clinical experiences of how the ISRs can be managed.

PMID- 21881989
TI  - Monoclonal gammopathies in a Moroccan military hospital.
AB  - The aim of this study was to describe biological features and aetiology of
      monoclonal gammopathy diagnosed during a 10-year period in the biochemistry
      department of the Moroccan Military Hospital Mohamed V in Rabat. The study was
      performed from 1 January 2000 to 31 December 2009. The records of 261 patients
      living in the Rabat area in which either serum protein electrophoresis and serum
      and/or urine immunofixation were performed at the biochemistry department of
      Military Instruction Hospital in Rabat were analysed. A cohort of 182 (70%) men
      and 79 (30%) women, the mean +/- SD (range) ages were 60.21 +/- 12.56 years. All
      patients were Caucasian. Electrophoresis found that 211 (80.84%) of the patients
      had a monoclonal gammopathy. Immunofixation confirmed that 251 (96.17%) patients
      had a monoclonal band in serum. In our cohort, MM was the most frequent
      diagnosis, our patients were late diagnosed.

PMID- 21881990
TI  - The effect of different treatment time of millimeter wave on chondrocyte
      apoptosis, caspase-3, caspase-8, and MMP-13 expression in rabbit surgically
      induced model of knee osteoarthritis.
AB  - The aim of this study is to observe the effect of different treatment time of
      millimeter wave (MMW) on chondrocyte apoptosis, caspase-3, caspase-8, and matrix
      metalloproteinase-13 (MMP-13) in rabbit knee osteoarthritis induced by anterior
      cruciate ligament transection (ACLT). Thirty-two New Zealand White rabbits were
      randomly assigned into 4 groups: millimeter wave treatment for 20-min group
      (MWT20); millimeter wave treatment for 40-min group (MWT40); model control group
      (MC) and normal control group (NC). All groups received anterior cruciate
      ligament transection in the right knee except NC group. Six weeks after
      transection, the MWT20 group and MWT40 group were given millimeter wave (MMW) at
      37.5 GHz frequency, 8 mm wavelength, and 10 mW/cm(2) power for 20 and 40 min,
      respectively, for 10 days. Eight weeks after transection, all animals were
      killed. Modified Mankin Score was assessed for histological assessment.
      Chondrocytes apoptosis was tested by the TUNEL assessment, and the expressions of
      related proteins were tested by the immunohistochemistry observation and Western
      blot. The modified Mankin Score, the chondrocyte apoptosis, and the expression of
      caspase-3 and MMP-13 in MWT40 group were significantly lower than those in MC
      group. Only a decreasing trend of modified Mankin Score and caspase-3 and MMP-13
      expression was found in MWT20 group. The caspase-8 expression of the treatment
      groups was lower than model control group and higher than normal control group,
      but no significant difference was found. This study revealed MWT40 had a better
      therapeutic benefit to osteoarthritis cartilage structure, decreased the
      apoptosis of chondrocyte, and caspase-3 and MMP-13 expression compared to MWT20.
      But only a decreasing trend of caspase-8 expression was found.

PMID- 21881991
TI  - Joint laxity in the parents of children with temporary brittle bone disease.
AB  - One controversial cause of unexplained fractures in young children is temporary
      brittle bone disease. Contributory factors for this disorder include the
      following: premature birth, twin pregnancy and diminished foetal movement.
      Heritable factors may also be important. Infants with findings consistent with
      temporary brittle bone disease were identified from clinical and medico-legal
      referrals. The routine evaluation of each family included examination of both
      parents where available for joint laxity using the nine-point Beighton scale. Of
      81 children in whom both parents had been examined personally, 40 had at least
      one parent with a Beighton score of four or more, conventionally regarded as
      indicative of the hypermobility syndrome. We found no significant difference in
      laxity when we compared the whole group of mothers with the controls (P = 0.081).
      The fathers were significantly different from their control group (P = 0.013).
      When we compared the figures for the most flexible parent of each child, there
      were significant differences from control subjects both in the mothers and in the
      fathers (P = 0.042 and P = 0.0065, respectively). We draw attention to the likely
      autosomal dominant inheritance of this risk factor for temporary brittle bone
      disease as well as the potential value of assessing parental joint laxity in
      evaluating children with fractures.

PMID- 21881992
TI  - Severe cartilage damage of the knee joint in two young women with hypermobility.
AB  - The purpose of this pictorial assay is to show the arthroscopic findings of two
      patients with hypermobility syndrome and patellofemoral malalignment. Severe
      chondral damage and recurrent bleeding were common findings in these patients.
      One patient also had a meniscal impingement syndrome. A dynamic assessment of the
      patellofemoral joint as well as the evaluation of the lateral and medial
      retinaculum was performed by arthroscopy. Pictures of damaged area on the
      articular cartilage were obtained through a 5-mm arthroscope using standard
      portals. A lack of the patellae retinaculum involvement was proved
      arthroscopically in both cases. Mechanical complaints and recurrent effusion,
      even without history of trauma, should alert physicians who manage patients with
      hypermobility. In patients with joint hypermobility, the damage of the cartilage
      is real and often a therapeutic challenge.

PMID- 21881993
TI  - Complement components 2 and 7 (C2 and C7) gene polymorphisms are not major risk
      factors for SLE susceptibility in the Malaysian population.
AB  - There have been numerous studies linking complement components and the
      pathogenesis of systemic lupus erythematosus (SLE). This is due to their numerous
      roles in modulating immune responses in the human body. This study examined the
      association of C2 and C7 genetic polymorphisms with the susceptibility to SLE
      based on two separate cohorts of patient and control samples from Malaysia. The
      28-bp deletion in the C2 exon-intron junction and single nucleotide polymorphism
      in the 3'untranslated region in the C7 genes were detected based on direct
      polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism,
      respectively. A total of 150 patient and 150 healthy control samples were
      screened, but there was no association detected between either genes. All
      individuals presented with null deletion in C2 genes, while the C allele and CC
      genotypes were most commonly scored. These overall results suggest a lack of
      strong association with the C2 and C7 gene polymorphisms to the susceptibility of
      SLE in the Malaysian population.

PMID- 21881995
TI  - Response to Van Rompaey Vincent to his accepted article: response to: Prognostic
      indicators of hearing after complete resection of cholesteatoma causing a
      labyrinthine fistula by Stephenson MF and Saliba I.

PMID- 21881997
TI  - On the history of modern tonsillectomy: the contribution of Nikolaos Taptas.
AB  - The earliest reports on removal of the entire tonsil using a method of careful
      dissection came in the early 1900 s by American and British
      otorhinolaryngologists. These descriptions are credited as the first of the so
      called modern tonsillectomy. In this report we present a technique of
      tonsillectomy conceived by Nikolaos Taptas, a Greek physician and citizen of the
      Ottoman Empire, which was introduced at the same period with the ones previously
      mentioned. Taptas practiced his technique in the very early 1900 s. He used his
      own instruments and reported excellent post-operative results with very few
      complications. He should therefore be considered among the pioneers of modern
      tonsillectomy.

PMID- 21881994
TI  - Lower expression of histamine H4 receptor in synovial tissues from patients with
      rheumatoid arthritis compared to those with osteoarthritis.
AB  - The aim of this study is to compare the expression level of histamine H(4)
      receptor (H(4)R) mRNA in synovial tissues of rheumatoid arthritis (RA) and
      osteoarthritis (OA) patients, and to study correlation of results with clinical
      characteristics of patients with RA. Synovial tissues were obtained from 7 RA and
      7 OA patients undergoing artificial arthroplasty. Serum levels of erythrocyte
      sedimentation rate, C-reactive protein, matrix metalloproteinase-3 (MMP-3),
      rheumatoid factors, and cyclic citrullinated peptide antibodies were determined.
      The expression of H(4)R mRNA in synovial tissues was determined by real-time
      polymerase chain reaction. Expression of H(1)R and H(4)R mRNA were significantly
      lower in RA compared with OA patients (P < 0.005), while expression of H(2)R mRNA
      was comparable in both. While a significant negative correlation was found
      between H(4)R expression and serum MMP-3 concentration (r = -0.70, P < 0.05), no
      correlation was found between MMP-3 and H(1)R (r = -0.52) or H(2)R (r = 0.23).
      This study supports the supposition that H(4)R in synovial tissue may play a role
      in cartilage and bone destruction by influencing the secretion of MMP-3 in
      patients with RA.

PMID- 21881998
TI  - Relationship between history, laryngoscopy and esophagogastroduodenoscopy for
      diagnosis of laryngopharyngeal reflux in patients with typical GERD.
AB  - The techniques used in the diagnosis of gastroesophageal reflux disease (GERD)
      have insufficient specificity and sensitivity in diagnosing laryngopharyngeal
      reflux (LPR). The purpose of this study was to evaluate the role of
      esophagogastroduodenoscopy (EGD) and laryngological examination in the diagnosis
      of LPR. A total of 684 diagnosed GERD and suspected LPR patients were
      prospectively scored by the reflux finding score (RFS) which was suggested by
      Koufman. A total of 484 patients with GERD who had RFS >= 7 were accepted as
      having LPR. 248 patients with GERD plus LPR on whom an endoscopic examination was
      performed were evaluated. As a control group, results from 82 patients with GERD
      who had RFS <7 were available for comparison. The GERD symptom score (RSS) was
      counted according to the existence of symptoms (heartburn/regurgitation) and
      frequency, duration, and severity. The reflux symptom index (RSI) suggested by
      Belafsky et al. was also evaluated. The relationship between esophageal
      endoscopic findings, RSS, RFS and RSI was investigated. Mean age was 46 +/- 12
      (19-80). The mean values of RSS, RFS, and RSI were 18.9 +/- 7.7, 10 +/- 2.2, 16.6
      +/- 11.9, respectively. Erosive esophagitis was detected in 75 cases (30%).
      Hiatus hernia was observed in 32 patients (13%). There was no correlation between
      RSS and RFS, RSI. The severity of esophagitis did not correlate with the severity
      of the laryngeal findings. LPR should be suspected when the history and
      laryngoscopy findings are suggestive of the diagnosis. EGD has no role in the
      diagnosis of LPR.

PMID- 21881999
TI  - Regulation of TGF-beta signaling by PKC depends on Tsc-22 inducibility.
AB  - Interactions between various signaling pathways enable a fine control of cellular
      activities. When the cells are subjected to activation of TGF-beta signaling and
      PKC signaling, PKC phosphorylation of Smad3 abrogates binding and transcriptional
      activity of Smad3 leading to suppression of TGF-beta response. We studied this
      interaction between Smads and PKC in different cell types to examine cell
      specificity of the interaction. We found that the outcome of the interaction
      between Smads and PKC depends on cell types and inducibility of a regulatory
      molecule Tsc-22. In this report, we showed that induced Tsc-22 leads to
      enhancement of TGF-beta-dependent signaling and the enhancement was blocked by
      expression of a dominant-negative Tsc-22 mutant. Its effect on cellular
      differentiation was also examined.

PMID- 21882000
TI  - Assessing the risk of phosphorus loss and identifying critical source areas in
      the Chaohu Lake watershed, China.
AB  - Agricultural nonpoint phosphorus (P) pollution is a primary cause of
      eutrophication in many freshwater systems. Identifying areas that are at high
      risk for P loss in a watershed and concentrating management efforts on these
      smaller sections is a more effective method for limiting P loss than implementing
      general strategies over a broad area. A modified P index scheme was used to
      assess the risk of P loss and identify critical source areas in the Chaohu Lake
      watershed on a regional scale. In the new P ranking scheme, soil P sorption index
      (PSI) and degree of P saturation (DPS) were introduced as source factors to
      represent the inherent ability of P transport in the soil-water interface.
      Distance from P sources to Chaohu Lake was also considered as a transport factor
      to take into account P degradation from source to the final receiving water. The
      ranking scheme was modified to use available data on the regional scale. P index
      calculation results showed high spatial variation of P loss risk in the Chaohu
      Lake watershed. The highest risk areas focused on the downstream parts of the
      main rivers that discharge into Chaohu Lake. The induction of new components into
      the P index calculation makes it possible to identify critical source areas of
      nonpoint P loss on a regional scale, thus allowing decision makers to implement
      best management practices (BMPs) in such a manner as to minimize P loss to
      sensitive watercourses.

PMID- 21882001
TI  - Forest ecosystem services and eco-compensation mechanisms in China.
AB  - Forests are a major terrestrial ecosystem providing multiple ecosystem services.
      However, the importance of forests is frequently underestimated from an economic
      perspective because of the externalities and public good properties of these
      services. Forest eco-compensation is a transfer mechanism that serves to
      internalize the externalities of forest ecosystem services by compensating
      individuals or companies for the losses or costs resulting from the provision of
      these services. China's current forest eco-compensation system is centered mainly
      on noncommercial forest. The primary measures associated with ecosystem services
      are (1) a charge on destructive activities, such as indiscriminate logging, and
      (2) compensation for individual or local activities and investments in forest
      conservation. The Compensation Fund System for Forest Ecological Benefits was
      first listed in the Forest Law of the People's Republic of China in 1998. In
      2004, the Central Government Financial Compensation Fund, an important source for
      the Compensation Fund for Forest Ecological Benefits, was formally established.
      To improve the forest eco-compensation system, it is crucial to design and
      establish compensation criteria for noncommercial forests. These criteria should
      take both theoretical and practical concerns into account, and they should be
      based on the quantitative valuation of ecosystem services. Although some initial
      headway has been made on this task, the implementation of an effective forest eco
      compensation system in China still has deficiencies and still faces problems.
      Implementing classification-based and dynamic management for key noncommercial
      forests and establishing an eco-compensation mechanism with multiple funding
      sources in the market economy are the key measures needed to conquer these
      problems and improve the forest eco-compensation system and China's forestry
      development in sequence.

PMID- 21882002
TI  - Clinical and scientific progress related to the interface between cardiology and
      psychology: lessons learned from 35 years of experience at the Thoraxcenter of
      the Erasmus Medical Center in Rotterdam.
AB  - In November 1975, as the first in the Netherlands, a full-time psychologist was
      employed at the Department of Cardiology of the Thoraxcenter of the Erasmus
      Medical Center. This innovative decision was consistent with a view to treat the
      patient as a whole rather than the heart as a single body part in need of repair,
      combined with the understanding that the heart and mind interact to affect
      health. The present selective review addresses the broad range of contributions
      of 35 years of psychology to clinical cardiology and cardiovascular research with
      a focus on research, teaching, psychological screening and patient care. The
      review ends with lessons to be learned and challenges for the future with respect
      to improving the care and management of patients with heart disease in order to
      enhance secondary prevention and the role of behavioural and psychological
      factors in this endeavour.

PMID- 21882003
TI  - RBAC-Matrix-based EMR right management system to improve HIPAA compliance.
AB  - Security control of Electronic Medical Record (EMR) is a mechanism used to manage
      electronic medical records files and protect sensitive medical records document
      from information leakage. Researches proposed the Role-Based Access
      Control(RBAC). However, with the increasing scale of medical institutions, the
      access control behavior is difficult to have a detailed declaration among roles
      in RBAC. Furthermore, with the stringent specifications such as the U.S. HIPAA
      and Canada PIPEDA etc., patients are encouraged to have the right in regulating
      the access control of his EMR. In response to these problems, we propose an EMR
      digital rights management system, which is a RBAC-based extension to a matrix
      organization of medical institutions, known as RBAC-Matrix. With the aim of
      authorizing the EMR among roles in the organization, RBAC-Matrix also allow
      patients to be involved in defining access rights of his records. RBAC-Matrix
      authorizes access control declaration among matrix organizations of medical
      institutions by using XrML file in association with each EMR. It processes XrML
      rights declaration file-based authorization of behavior in the two-stage design,
      called master & servant stage, thus makes the associated EMR to be better
      protected. RBAC-Matrix will also make medical record file and its associated XrML
      declaration to two different EMRA(EMR Authorization)roles, namely, the medical
      records Document Creator (DC) and the medical records Document Right Setting
      (DRS). Access right setting, determined by the DRS, is cosigned by the patient,
      thus make the declaration of rights and the use of EMR to comply with HIPAA
      specifications.

PMID- 21882004
TI  - The effect of artificial neural network model combined with six tumor markers in
      auxiliary diagnosis of lung cancer.
AB  - To evaluate the diagnosis potential of artificial neural network (ANN) model
      combined with six tumor markers in auxiliary diagnosis of lung cancer, to
      differentiate lung cancer from lung benign disease, normal control, and
      gastrointestinal cancers. Serum carcino-embryonic antigen (CEA), gastrin, neurone
      specific enolase (NSE), sialic acid (SA), Cu/Zn, Ca were measured through
      different experimental procedures in 117 lung cancer patients, 93 lung benign
      disease patients, 111 normal control, 47 gastric cancer patients, 50 patients
      with colon cancer and 50 esophagus cancer patients, 19 parameters of basic
      information were surveyed among lung cancer, lung benign disease and normal
      control, then developed and evaluated ANN models to distinguish lung cancer.
      Using the ANN model with the six serum tumor markers and 19 parameters to
      distinguish lung cancer from benign lung disease and healthy people, the
      sensitivity was 98.3%, the specificity was 99.5% and the accuracy was 96.9%.
      Another three ANN models with the six serum tumor markers were employed to
      differentiate lung cancer from three gastrointestinal cancers, the sensitivity,
      specificity and accuracy of distinguishing lung cancer from gastric cancer by the
      ANN model of lung cancer-gastric cancer were 100%, 83.3% and 93.5%, respectively;
      The sensitivity, specificity and accuracy of discriminating lung cancer by lung
      cancer-colon cancer ANN model were 90.0%, 90.0%, and 90.0%; And which were 86.7%,
      84.6%, and 86.0%, respectively, by lung cancer-esophagus cancer ANN model. ANN
      model built with the six serum tumor markers could distinguish lung cancer, not
      only from lung benign disease and normal people, but also from three common
      gastrointestinal cancers. And our evidence indicates the ANN model maybe is an
      excellent and intelligent system to discriminate lung cancer.

PMID- 21882005
TI  - Determination of women iron deficiency anemia using neural networks.
AB  - Iron deficiency anemia (IDA) is a common type of anemia which most often occurs
      in young adult women. Detection of Iron deficiency requires blood tests and
      doctors' decision. Doing so can be costly and difficult especially in undeveloped
      countries. In this study, we developed an application by using Feedforward
      Networks (FFN), Cascade Forward Networks (CFN), Distributed Delay Networks (DDN),
      Time Delay Networks (TDN), Probabilistic Neural Network (PNN), and Learning
      Vector Quantization (LVQ) networks that can diagnose iron deficiency anemia in
      women.

PMID- 21882006
TI  - Brettanomyces as a starter culture in rice-steamed sponge cake: a traditional
      fermented food in China.
AB  - The potential use of Brettanomyces anomalus PSY-001 as an additional starter
      culture for the production of Rice-steamed sponge cake (RSSC), a traditional
      fermented food in China, was investigated. Two productions of RSSC, each
      containing batches of experimental cakes with Brettanomyces added and reference
      cakes with the leavened liquid added were carried out. For both experimental and
      reference cakes, chemical analysis and sensory evaluation were carried out during
      the fermentation period. The results showed that experimental cakes had desirable
      aroma and taste. The observed differences indicate a positive contribution to the
      overall quality of RSSC by B. anomalus PSY-001.

PMID- 21882007
TI  - Polyphosphate deficiency affects the sliding motility and biofilm formation of
      Mycobacterium smegmatis.
AB  - Inorganic polyphosphate (polyP) is a ubiquitous linear polymer of hundreds of
      orthophosphate (Pi) residues linked by ATP-like, high-energy, phosphoanhydride
      bonds. The gene Rv1026 in Mycobacterium tuberculosis encodes a putative
      exopolyphosphatase which progressively hydrolyzes the terminal residues of polyP
      to liberate Pi. Rv1026 was cloned into the expressive plasmid pMV261. The
      resulting plasmid pRv1026 and the plasmid pMV261 were transformed into M.
      smegmatis strain mc(2)155 by electroporation. The recombinant M. smegmatis
      (pRv1026) showed relatively decreased polyP concentration and a phenotype
      different from the M. smegmatis (pMV261) in sliding motility and biofilm
      formation. The surfactant Tween 80 can enhance this effect on the sliding
      motility and biofilm formation of M. smegmatis. There are four different peaks
      between the gas chromatography of cellular wall fatty acid of the M. smegmatis
      (pRv1026) and the M. smegmatis (pMV261). These results indicate that polyP
      deficiency can affect the fatty acid composition of cellular wall and these
      alteration of cell wall might elucidate the reductive ability of strains to slide
      and form biofilm. This investigation provides novel recognition about the role of
      Rv1026, which provides novel clues for further study on the physiological role of
      Rv1026 in M. tuberculosis.

PMID- 21882008
TI  - Prevalence of acanthamoeba from tap water in rio grande do Sul, Brazil.
AB  - A total of 136 samples of tap water were collected from state and municipal
      schools between March and November 2009. The samples were filtered through
      cellulose nitrate membranes that were seeded at non-nutrient agar 1.5% containing
      an overlayer of Escherichia coli suspension. Thirty-one (22.79%) tap water
      samples investigated were found positive for free-living amoebae (FLA). From
      these, 13 presented as FLA that seems to belong to the genus Acanthamoeba. All
      samples of FLA were cloned and identified as belonging to the genus Acanthamoeba
      by the morphology of cysts and trophozoites and by PCR using genus-specific
      primers that amplify the ASA.S1 region of 18S rDNA gene. Physiological tests of
      thermotolerance and osmotolerance were used to evaluate the pathogenicity of the
      isolates. The sequencing analysis by comparing the sequences submitted to
      GenBank, showed genotype distribution into groups T2, T2/T6, T6, and T4. In tests
      of thermotolerance and osmotolerance, 50% of the isolates had a low pathogenic
      potential. The results indicated the presence of Acanthamoeba in tap water in Rio
      Grande do Sul, Brazil, revealing its importance and the need for more
      epidemiological studies to determine their distribution in the environment and
      its pathogenic potential.

PMID- 21882009
TI  - Key issues in the design of pay for performance programs.
AB  - Pay for performance (P4P) is increasingly being used to stimulate healthcare
      providers to improve their performance. However, evidence on P4P effectiveness
      remains inconclusive. Flaws in program design may have contributed to this
      limited success. Based on a synthesis of relevant theoretical and empirical
      literature, this paper discusses key issues in P4P-program design. The analysis
      reveals that designing a fair and effective program is a complex undertaking. The
      following tentative conclusions are made: (1) performance is ideally defined
      broadly, provided that the set of measures remains comprehensible, (2) concerns
      that P4P encourages "selection" and "teaching to the test" should not be
      dismissed, (3) sophisticated risk adjustment is important, especially in outcome
      and resource use measures, (4) involving providers in program design is vital,
      (5) on balance, group incentives are preferred over individual incentives, (6)
      whether to use rewards or penalties is context-dependent, (7) payouts should be
      frequent and low-powered, (8) absolute targets are generally preferred over
      relative targets, (9) multiple targets are preferred over single targets, and
      (10) P4P should be a permanent component of provider compensation and is ideally
      "decoupled" form base payments. However, the design of P4P programs should be
      tailored to the specific setting of implementation, and empirical research is
      needed to confirm the conclusions.

PMID- 21882010
TI  - Can we predict and prevent adverse events related to high-voltage implantable
      cardioverter defibrillator lead failure?
AB  - BACKGROUND: In 2007, great concern arose regarding failure of implantable
      cardioverter defibrillator (ICD) leads from several manufacturers. OBJECTIVE: Of
      this analysis was to evaluate the incidence and predictors of Sprint Fidelis lead
      failure in order to find the best clinical strategy to prevent lead-related
      adverse events. METHODS: Four hundred fourteen patients (357 male, 67 +/- 12
      years) with ICD equipped with right ventricular Sprint Fidelis leads were
      followed up in our institution. RESULTS: Over a median follow-up of 35 months
      (25th-75th percentile = 27-47 months) and a total follow-up of 1,231 patient
      years, lead failures occurred in 40 of 414 (9.7%) patients. The annual rate was
      3.2% per patient-year. Thirty-five (87.5%) failures were caused by pacing-sensing
      connector fracture. The risk of lead fracture was higher in patients younger than
      70 years (odds ratio = 2.31; 95% confidence interval = 1.14-4.68, p = 0.02).
      Among 30 patients with pacing-sensing conductor failure and available device
      diagnostics for failure alerting, the diagnostic parameter which first responded
      to lead failure was the sensing integrity counter in 15 of 30 (50%), pacing
      impedance in 12 of 30 (40%), and non-sustained ventricular tachycardia in 3 of 30
      (10%). The median time (25th-75th percentile) between diagnostics alert and lead
      failure-related adverse events or failure acknowledgment was 2.2 (0.3-13.0) days.
      Twenty-two patients suffered inappropriate shocks due to lead failure. In 50% of
      patients, daily monitoring by device diagnostics would have alerted physicians to
      impending lead failure at least 1 day in advance. CONCLUSIONS: Automatic
      algorithms based on device diagnostics may detect impending lead failure in
      nearly 50% of cases. Remote monitoring may prevent failure-related adverse
      events.

PMID- 21882011
TI  - The relationship of impulsivity-inattention and verbal ability to overt and
      covert antisocial behaviors in children.
AB  - Research has linked many risk factors in childhood and early adolescence to
      antisocial behaviors in later adolescence and early adulthood; however, less
      attention has focused on the interaction among factors in the prediction of
      distinct forms of antisocial behaviors. This study investigated the additive and
      synergistic association of inattention-impulsivity and verbal ability with overt
      and covert antisocial behaviors using a high risk community sample of 270 (49.8%
      female) children. Multiple regression analyses indicated kindergarten inattention
      impulsivity was significantly related to overt and covert antisocial behaviors
      and the interaction of inattention-impulsivity and verbal ability significantly
      predicted covert but not overt antisocial behaviors during kindergarten and first
      grade. Kindergarten verbal ability did not buffer the association of impulsivity
      inattention with covert antisocial behavior; rather higher verbal ability was
      associated with increased risk for covert antisocial behavior in the presence of
      high levels of impulsivity-inattention. The association of inattention
      impulsivity with higher levels of overt and covert antisocial behavior begins
      during childhood, and may set off developmental trajectories associated with the
      acceleration of antisocial behavior in adolescence.

PMID- 21882012
TI  - Blood vessel wall-derived endothelial colony-forming cells enhance fracture
      repair and bone regeneration.
AB  - Endochondral bone formation requires new blood vessel formation, and endothelial
      progenitor cells (EPCs) may play a role in this process. Endothelial colony
      forming cells (ECFCs), one subtype of EPCs, isolated from the microvasculature of
      rat lungs, exhibited cell surface antigen markers and gene products
      characteristic of endothelial cells and displayed high proliferative potential
      and an ability to form vessel-like network structures in vitro. The aim of this
      study was to evaluate whether ECFCs facilitate bone healing during fracture
      repair and stimulate bone regeneration. When type I collagen sponge containing
      ECFCs were surgically wrapped around the fractured femurs of rats, newly formed
      bone mineral at the site of fracture was 13% greater (P = 0.01) and energy to
      failure was 46% greater (P = 0.01) compared to sponge-wrapped fractures without
      ECFCs. When ECFCs in type I collagen sponge were surgically implanted into the
      bone defective area, more new vessels formed locally in comparison with sponge
      alone controls and new bone tissues were seen. Further, co-implantation of ECFCs
      and hydroxyapatite/tricalcium phosphate (HA/TCP) scaffolds at the bone defective
      sites stimulated more new bone tissues than HA/TCP scaffold alone. These results
      show that cell therapy with vessel wall-derived ECFCs can induce new vessel
      formation, stimulate new bone formation, and facilitate bone repair and could be
      a useful approach to treat non-union fractures and bone defects.

PMID- 21882013
TI  - Microalgae as platforms for production of recombinant proteins and valuable
      compounds: progress and prospects.
AB  - Over the last few years microalgae have gained increasing interest as a natural
      source of valuable compounds and as bioreactors for recombinant protein
      production. Natural high-value compounds including pigments, long-chain
      polyunsaturated fatty acids, and polysaccharides, which have a wide range of
      applications in the food, feed, cosmetics, and pharmaceutical industries, are
      currently produced with nontransgenic microalgae. However, transgenic microalgae
      can be used as bioreactors for the production of therapeutic and industrially
      relevant recombinant proteins. This technology shows great promise to simplify
      the production process and significantly decrease the production costs. To date,
      a variety of recombinant proteins have been produced experimentally from the
      nuclear or chloroplast genome of transgenic Chlamydomonas reinhardtii. These
      include monoclonal antibodies, vaccines, hormones, pharmaceutical proteins, and
      others. In this review, we outline recent progress in the production of
      recombinant proteins with transgenic microalgae as bioreactors, methods for
      genetic transformation of microalgae, and strategies for highly efficient
      expression of heterologous genes. In particular, we highlight the importance of
      maximizing the value of transgenic microalgae through producing recombinant
      proteins together with recovery of natural high-value compounds. Finally, we
      outline some important issues that need to be addressed before commercial-scale
      production of high-value recombinant proteins and compounds from transgenic
      microalgae can be realized.

PMID- 21882014
TI  - Biotransformation of puerarin into puerarin-6"-O-phosphate by Bacillus cereus.
AB  - The biotransformation of puerarin catalyzed by Bacillus cereus NT02 was studied.
      A primary screening was carried out using 307 strains of bacteria isolated from
      soil which were able to grow in the presence of puerarin. Strain NT02, identified
      as B. cereus, was able to convert puerarin into puerarin-6"-O-phosphate. Under
      the optimum conditions, resting cells of B. cereus NT02 converted 27% of added
      0.4 g/l puerarin into puerarin-6"-O-phosphate that was characterized by MS, 13C
      NMR, 31P NMR. The activity of puerarin-6"-O-phosphate was 25 times higher than
      that of puerarin in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging
      system. The water solubility of puerarin-6"-O-phosphate was 85.4 times higher
      than that of puerarin.

PMID- 21882015
TI  - Relationship between meiotic spindle characteristics in human oocytes and the
      timing of the first zygotic cleavage after intracytoplasmic sperm injection.
AB  - PURPOSE: To investigate the relationship between meiotic spindle characteristics
      in human oocytes and the timing of the first zygotic cleavage after
      intracytoplasmic sperm injection (ICSI). METHODS: Zygotes that had cleaved to two
      cell stage by 27 h post-ICSI were classified as early cleaving and the remainder
      as late cleaving. Meiotic spindle parameters previously imaged using the PolScope
      were compared between the two groups. RESULTS: Of 384 embryos, 163 were classed
      as early cleaving and 221 as late cleaving. The rate of blastocyst formation or
      pregnancy by Day 2 embryo transfer was significantly higher following early
      cleavage than after late cleavage (52.4% vs. 24.4% or 32.6% vs. 11.4%). Spindle
      areas (108.0 vs. 89.8 MUm(2)), lengths (14.7 vs. 13.4 MUm) and PolScope
      retardance were also significantly greater in the early cleaving group.
      CONCLUSIONS: Meiotic spindle parameters determine the timing of the first zygotic
      cleavage and are strong indicators of human embryo developmental potential.

PMID- 21882016
TI  - ART, birth defects and subfertility--what should prospective patients be told?

PMID- 21882017
TI  - Serum anti-Mullerian hormone and antral follicle count as predictive markers of
      OHSS in ART cycles.
AB  - OBJECTIVE: To evaluate predictive role of day-3 serum anti-Mullerian hormone
      (AMH) levels and antral follicle count (AFC) in ovarian hyperstimulation syndrome
      (OHSS) in patients undergoing IVF/ICSI cycles. MATERIALS AND METHODS: Forty-one
      women with moderate/severe OHSS and 41 age matched women without OHSS were
      compared to evaluate the predictive value of certain risk factors for OHSS. AFC,
      and E(2), FSH, LH, AMH, inhibin-B levels measured on day 3 of the menstrual cycle
      before controlled ovarian hyperstimulation. RESULTS: Mean FSH was significantly
      lower (p < 0.0001); and mean LH, AFC and AMH were significantly higher in women
      with OHSS compared to women without OHSS (p = 0.049, p < 0.0001 and p < 0.0001,
      respectively). There was no significant difference in inhibin B (p = 0.112) and
      estradiol (p = 0.706) between the groups. The ROC area under curve (AUC) for AMH
      presented the largest AUC among the listed risk factors. AMH (AUC = 0.87) and AFC
      (AUC = 0.74) had moderate accuracy for predicting OHSS while Inhibin B (AUC =
      0.58) and LH (AUC = 0.61) had low accuracy. The cut-off value for AMH 3.3 ng/mL
      provided the highest sensitivity (90%) and specificity (71%) for predicting OHSS.
      It's positive (PPV) and negative predictive values (NPV) were 61% and 94%,
      respectively. The cut-off value for AFC was 8 with 78% sensitivity, 65%
      specificity, 52% PPV and 86% NPV. CONCLUSION: Measurement of basal serum AMH and
      AFC can be used to determine the women with high risk for OHSS.

PMID- 21882018
TI  - The impact of hospital utilization on patient readmission rate.
AB  - We investigate the issue of patient readmission at a large academic hospital in
      the U.S. Specifically, we look for evidence that patients discharged when post
      operative unit utilization is high are more likely to be readmitted. After
      examining data from 7,800 surgeries performed in 2007, we conclude that patients
      who are discharged from a highly utilized post-operative unit are more likely to
      be readmitted within 72 h. Each additional bed utilized at time of discharge
      increases the odds of readmission on average by 0.35% (Odds Ratio = 1.008, 95% CI
      [1.003, 1.012]). We propose that this effect is due to an increased discharge
      rate when the unit is highly utilized.

PMID- 21882019
TI  - Components separation technique combined with a double-mesh repair for large
      midline incisional hernia repair.
AB  - BACKGROUND: The surgical treatment of large midline incisional hernias remains a
      challenge. The aim of this report is to present the results of a new technique
      for large midline incisional hernia repair which combines the components
      separation technique with a double-prosthetic-mesh repair. METHODS: The records
      of all consecutive patients who received a double-mesh combined with the
      components-separation technique for ventral hernia repair were reviewed. The
      clinical, surgical, and follow-up data were analyzed. RESULTS: Nine patients [3
      women, 6 men; median age = 62 years (range = 26-77)] were included in the study.
      Median transverse defect size was 20 cm (range = 15-25). The median duration of
      hospital stay was 8 days (range = 5-17). Postoperative complications occurred in
      66% (6/9). Follow-up [median = 13 months (range = 3-49)] showed no recurrent
      hernias, but one patient had a small hernia after a relaparotomy for colon
      carcinoma recurrence. The overall occurrence of wound infections was 44% (4/9).
      There was no mortality. CONCLUSION: The components-separation technique in
      combination with a double-mesh has shown a low recurrence rate in the short-term
      follow-up. However, there is a considerable occurrence of postoperative wound
      infections. Long-term results of the hernia recurrence rate have to be awaited.

PMID- 21882020
TI  - Surgical impact on gastric cancer with locoregional invasion.
AB  - BACKGROUND: The benefit of resection of gastric cancer with locoregional invasion
      is still under debate. This study aimed to investigate the impact of surgery on
      patients with gastric cancer with locoregional invasion. METHODS: From January
      1988 to December 2009, a total of 2,678 patients with gastric cancer underwent
      surgery at the Department of Surgery, Taipei Veterans General Hospital. Among
      these patients, 569 and 295 were diagnosed as T4a (serosa invasion without
      penetration of visceral peritoneum) and T4b (serosa exposure with invasion of
      adjacent structure), respectively. Invasion type and prognosis were analyzed in
      patients with gastric cancer who had either curative or palliative resection.
      RESULTS: Our results showed that patients with T4a gastric cancer had a better 5
      year overall survival than patients with T4b (22.5% vs. 11.5%, P < 0.001).
      Patients with T4b who had curative resection had a better 5-year overall survival
      than those with T4b who had palliative resection (13.8% vs. 7.3%, P = 0.001). The
      prognosis of patients with gastric cancer with pancreas invasion was worse than
      those with mesocolon invasion, as no patients with pancreas invasion survived
      more than 5 years. Univariate and multivariate analyses showed that tumor size (P
      = 0.019), Bormann classification (P < 0.001), stromal reaction (P = 0.001), and
      nodal involvement (P < 0.001) were independent predictors for overall survival in
      patients with T4b gastric cancer. CONCLUSION: Resection of T4b gastric cancer
      could be performed with curative intent. Patients with gastric cancer with
      pancreas invasion had a poorer prognosis than those with mesocolon invasion.

PMID- 21882021
TI  - Renal vein lengthening using gonadal vein reduces surgical difficulty in living
      donor kidney transplantation.
AB  - BACKGROUND: During living-donor kidney transplantation, to maximally decrease
      donor injury, the right kidney with lower glomerular filtration rate often is
      selected as the donor kidney. However, the renal vein of the right kidney is
      relatively short for transplantation. The gonadal vein is essentially useless and
      is easily accessed during the donor nephrectomy. METHODS: Seventeen live kidney
      donors received right kidney nephrectomy for living-donor kidney transplantation.
      Short renal veins were lengthened by circular anastomosis or spiral anastomosis
      of longitudinally cut gonadal veins. The renal function of receivers was
      evaluated using creatinine clearance. RESULTS: The renal veins were extended by
      2.0-2.7 cm with circular anastomosis and 4.1-4.5 cm with spiral anastomosis with
      an average of 2.5 +/- 0.7 cm. Lengthening of renal veins averaged 20.4 +/- 4.2
      min. All surgeries were successful, significantly reducing difficulty of vascular
      anastomosis during transplantation. No poor early graft function occurred. No
      side effects were observed in donors. CONCLUSIONS: When donor renal veins are too
      short for effective kidney transplantation and may affect reliability of vascular
      anastomosis, they can be lengthened by using gonadal veins without increasing
      injury to the donor. Successful extension of donor kidney renal veins expands the
      indication for right donor kidneys.

PMID- 21882022
TI  - Fast-track concepts in major open upper abdominal and thoracoabdominal surgery: a
      review.
AB  - INTRODUCTION: The purpose of this article was to review the research considering
      fast-track concepts in upper abdominal and thoracoabdominal surgery. METHODS: A
      search for clinical studies evaluating the fast-track concept after open major
      upper abdominal or thoracoabdominal surgery was performed. Reference lists of
      identified articles were searched. Trials-written in English-that compared a
      concept and traditional care were evaluated with regard to their internal
      validity. Level of evidence was defined and each outcome was evaluated. RESULTS:
      In total, 15 articles were found, separated into gastric (n = 2), pancreatic (n =
      5), hepatic (n = 2), esophageal (n = 3), and aortic surgery (n = 3). Three were
      randomized, controlled trials. The different trials represented various concepts
      of fast-track surgery, but the majority included specific programs for
      analgesics, avoidance of drainage tubes, early start of oral nutrition, and early
      and active mobilization. There is moderate evidence that fast-track concepts
      result in shorter hospital stay. There is low evidence that fast-track concepts
      shorten need of ventilation, decrease the need of care at the intensive care
      unit, decrease postoperative pain, and reduce total hospital costs. The concepts
      seem to have similar rates of surgical complications, readmission rate, and
      mortality rates as conventional care. No specific adverse events were reported.
      CONCLUSIONS: Although the methodological quality of the articles reviewed was low
      and the trials heterogeneous, all trials concluded that the introduction of fast
      track concepts were safe and feasible, achieved shorter hospital stays, and
      reduced costs. Future randomized, controlled trials are needed to further
      evaluate the effect of these concepts.

PMID- 21882023
TI  - Community-acquired pneumonia during long-term follow-up of patients after radical
      esophagectomy for esophageal cancer: analysis of incidence and associated risk
      factors.
AB  - BACKGROUND: There are no data concerning the occurrence of community-acquired
      pneumonia (CAP) in esophageal cancer patients during long-term follow-up after
      radical esophagectomy. The aims of the present study were to determine the
      incidence of CAP in esophageal cancer patients who underwent radical
      esophagectomy and to identify the risk factors. METHODS: A total of 186
      consecutive patients who underwent radical esophagectomy for thoracic esophageal
      carcinoma in our hospital between 1991 and 2000 were enrolled in this study. Data
      on the occurrence of CAP were retrospectively collected from medical records,
      follow-up files, and telephone interviews with patients. The cumulative incidence
      of CAP was calculated by the Kaplan-Meier method, and the risk factors for CAP
      were determined by univariate and multivariate analyses. The median follow-up
      time was 77 months (range 12-216 months). RESULTS: Sixty patients suffered from
      CAP during the follow-up period. The cumulative incidence was 25.8% at 5 years
      and 38.4% at 10 years. Multivariate analysis revealed the following as the
      significant risk factors for CAP: presence of lymph node metastasis (Hazard ratio
      [HR], 2.64; 95% confidence interval [CI], 1.55-4.50; P < 0.001), colonic
      interposition (HR, 2.87; 95% CI, 1.41-5.82; P = 0.004), obstructive lung disease
      (HR, 1.95; 95% CI, 1.11-3.42; P = 0.021), and preoperative hypoalbuminemia (HR,
      2.08; 95% CI, 1.20-3.60; P = 0.009). CONCLUSIONS: There is a high incidence of
      CAP in esophageal cancer patients after esophagectomy. Positive nodal metastasis,
      colonic interposition, obstructive lung disease, and preoperative hypoalbuminemia
      are risk factors for this long-term postoperative morbidity.

PMID- 21882024
TI  - Large clinical experience of primary angiosarcoma of the breast in a single
      Korean medical institute.
AB  - BACKGROUND: Angiosarcoma of the breast is rare. The purpose of the present study
      was to evaluate the clinicopathologic characteristics and the clinical outcomes
      of patients with primary breast angiosarcoma. METHODS: We analyzed the
      clinicopathologic factors of patients with angiosarcoma of the breast treated
      between 1997 and 2010 at the Samsung Medical Center. We reviewed the related
      demographic data, preoperative imaging studies, method of histologic
      confirmation, tumor size, histologic grades, status of hormonal receptors,
      treatment modality, and survival data. RESULTS: Nine women with angiosarcoma of
      the breast were identified. The median age of patients with primary angiosarcoma
      of the breast at diagnosis was 31 years (range: 19-63 years), and the median
      tumor size was 9.0 cm (range: 3.5-10.7 cm). Seven patients (77.7%) died within a
      median follow-up of 46.7 months (range: 3.9-63.3 months), and all deaths were
      directly attributed to angiosarcoma. Overall, the median time from diagnosis of
      angiosarcoma to death was 46.8 months (range: 8.21-63.3 months). The 5 year
      overall survival with angiosarcoma was 42.9%. CONCLUSIONS: Primary angiosarcoma
      of the breast is a rare malignancy with a poor prognosis, even with complete
      resection. Chemotherapy and radiation therapy have limited value as treatments to
      date. Total mastectomy appears to be the most appropriate and beneficial
      treatment. More aggressive surgical management should be considered, and future
      clinical research should explore the most appropriate adjuvant therapy in the
      treatment of angiosarcoma.

PMID- 21882025
TI  - Comparison between laparoscopy and noninvasive tests for the diagnosis of
      tuberculous peritonitis.
AB  - BACKGROUND: Despite recent progress, the fast and accurate diagnosis of
      tuberculous peritonitis (TBP) continues to be a challenge, mainly because of the
      lack of specific clinical features and the difficulty in isolating the M.
      tuberculosis. The present study aimed to investigate the role of laparoscopy in
      the diagnosis of TBP, compared to noninvasive tests. METHODS: We retrospectively
      studied 60 patients who had diagnostic laparoscopy for suspected TBP between
      January 2002 and June 2010. RESULTS: Forty-one patients were diagnosed with TBP.
      In terms of accuracy and predictive value, the visual diagnosis via laparoscope
      was the most diagnostic test. In the noninvasive tests, both the ascitic
      adenosine deaminase (ADA) level over 30 U/l, and the ascitic lactate
      dehydrogenase (LDH) level over 90 U/l had relatively high positive, as well as
      negative, predictive values. The overall morbidity and mortality rates for
      laparoscopy were 5 and 5%, respectively. CONCLUSIONS: Laparoscopy is a rapid and
      accurate diagnostic test for TBP. However, complications may occur. In older
      patients with associated conditions, a combination of various noninvasive tests
      and empirical treatments is needed prior to laparoscopy.

PMID- 21882026
TI  - Laparoscopy-assisted proximal gastrectomy with sentinel node mapping for early
      gastric cancer.
AB  - BACKGROUND: Laparoscopy-assisted proximal gastrectomy (LAPG) remains a relatively
      uncommon procedure because of certain technical issues, such as curability,
      safety, and retention of postoperative patients' quality of life. The aim of the
      present study was to evaluate the feasibility of a newly developed LAPG procedure
      for early-stage proximal gastric cancer. METHODS: We enrolled 37 consecutive
      patients who were preoperatively diagnosed with cT1N0M0 primary gastric cancer in
      the upper third of the stomach with the primary tumor diameter less than 4 cm.
      Laparoscopy-assisted proximal gastrectomy with sentinel node (SN) mapping and
      esophagogastric anastomosis with a circular stapler and transoral placement of
      the anvil was attempted. RESULTS: The LAPG procedure was completed in 36
      patients. It was converted to laparoscopy-assisted total gastrectomy in one
      patient because one SN detected intraoperatively was positive for metastasis by
      intraoperative pathological diagnosis. There were no severe postoperative
      complications in any patient. Only one patient (3%) complained of mild reflux
      symptoms immediately after operation, which were graded endoscopically as B by
      the Los Angeles Classification of gastroesophageal reflux disease; however, the
      symptoms were controlled well by a proton-pump inhibitor. Sentinel nodes were
      detected successfully in 37 (100%) of our patients. The mean number of dissected
      lymph nodes and identified SNs per case was 29.7 and 5.8, respectively. The
      sensitivity of prediction of nodal metastasis (including isolated tumor cells)
      and diagnostic accuracy based on SN status were 100% (3/3) and 100% (37/37),
      respectively. All patients have been free from recurrence for a median follow-up
      period of 26 months. CONCLUSIONS: This study reveals that our novel LAPG approach
      is curative and represents a feasible minimally invasive surgical procedure with
      minimal morbidity and postoperative reflux esophagitis in patients with upper
      third early-stage gastric cancer.

PMID- 21882027
TI  - Post-pancreaticoduodenectomy hemorrhage. Incidence, diagnosis, and treatment.
AB  - BACKGROUND: Although mortality post-pancreaticoduodenectomy (PD) has decreased,
      morbidity rates continue to be high, ranging from 30% to 50%. Among
      complications, hemorrhage stands out; it is associated with high mortality and
      there is no standard management. The aim of the present study was to analyze the
      incidence, diagnosis, and treatment of hemorrhage post-cephalic PD at our center.
      METHODS: From January 2005 to December 2008, 107 PDs were performed. A
      retrospective review of characteristics of patients with postoperative hemorrhage
      was made from our prospective database. Demographic data, diagnosis, treatment
      (medical, laparotomy, interventional radiology), association with fistula
      (pancreatic or biliary), intra- or extraluminal hemorrhage, bleeding time (early
      or late), severity (moderate/severe), and mortality were analyzed. RESULTS:
      Eighteen patients (18/107; 16.82%) hemorrhaged after PD. Hemorrhage appeared
      early (< 24 h) in 4 of these 18 patients (22.2%), and it was severe in 13/18
      (72%). Hemorrhage-related mortality was 11% (2/18) and hospital mortality was
      22.2% (4/18). Arteriography was performed in 8/18 patients (44.4%) and was
      effective in 6/8 (75%); laparotomy was performed in 8/18 (44.4%). Re-bleeding
      occurred in 5 of these 18 patients after the first treatment (27.8%). An
      association between hemorrhage and fistula was observed. CONCLUSIONS: Hemorrhage
      after pancreatic resection must be considered a complication with relatively high
      mortality. Diagnosis should be established and treatment applied rapidly.
      Pancreatic and/or biliary fistulae were significantly associated with a higher
      risk of postoperative hemorrhage. Interventional radiology is a good therapeutic
      option.

PMID- 21882029
TI  - Evaluation of current devices in single-incision laparoscopic colorectal surgery.

PMID- 21882028
TI  - Outcome of surgery for primary hyperaldosteronism.
AB  - BACKGROUND: Primary hyperaldosteronism (PHA) frequently causes secondary
      hypertension and is a surgically amenable disease if associated with unilateral
      adenoma. Patients who underwent laparoscopic adrenalectomy at the authors'
      department were followed to identify clinical parameters that predict resolution
      of hypertension. METHODS: All patients with PHA and adrenalectomy from 1993 to
      2009 were identified. Charts and follow-up data were reviewed for clinical
      parameters and hormone levels. Univariate and multivariate analysis were
      performed with SPSS 15.0. RESULTS: A cohort of 30 female and 24 male patients
      underwent laparoscopic adrenalectomy. Hypokalemia was observed in 47/54 (87%)
      patients. Twenty patients (37%) were cured without any further need of
      antihypertensive medication, 20 (37%) patients experienced an improvement in
      hypertension, and 14 (26%) patients remain unaffected. Consequently, hypertension
      was resolved or improved in 40/54 (74%) patients. A shorter duration of
      hypertension (<6 years), the number of antihypertensive drugs (<3), and the serum
      creatinine level (<1.3 mmol/l) were independent predictors of resolution of
      hypertension in a multivariate analysis. At final follow-up after a mean of 49 +/
      40 months, resolution of hypertension was observed in 17/30 (57%) patients.
      Interestingly, in 10/17 patients a period longer than 12 months was required
      before a resolution of hypertension was observed. Coexistent hyperplasia, which
      was observed in 30% of patients, did not correlate with outcome. CONCLUSIONS: In
      50% of patients with PHA, hypertension resolves after laparoscopic adrenalectomy,
      but the process may require more than 12 months. Patients with a duration of
      hypertension of more than 6 years, more than 3 antihypertensive drugs, and
      elevated serum creatinine have a higher risk of persistent hypertension after
      surgery. Coexistent hyperplasia in the resected adrenal gland is not associated
      with persistent hypertension.

PMID- 21882030
TI  - Nonsteroidal antiinflammatory medications: efficient and safe treatment following
      video-assisted pleurodesis for spontaneous pneumothorax.
AB  - BACKGROUND: Recurrent spontaneous pneumothorax is widely treated by video
      assisted thoracoscopic (VATS) bullectomy and pleurodesis. Treatment of
      postoperative pain with nonsteroidal antiinflammatory drugs (NSAIDs) is
      controversial as many surgeons believe that it reduces the efficacy of
      pleurodesis and increases the pneumothorax recurrence rate. METHODS: In this
      retrospective study, we reviewed the hospital records for patients following VATS
      pleurodesis for recurrent spontaneous pneumothorax. The patients were divided
      into two groups: (1) NSAID group: patients were treated with NSAIDs for more than
      a week following surgery and (2) control group: patients did not receive NSAIDs.
      Data regarding short- and long-term outcomes were compared. RESULTS: The study
      cohort included 105 patients: 48 in the NSAID group and 57 in the control group.
      During the early postoperative period the average daily requirement of narcotic
      analgesia and the incidence of narcotic-related side effects were lower in the
      NSAIDs group. No difference was found in the long-term recurrence rate: two of 48
      (4%) in the NSAID group and three of 57 (5%) in the control group. There was one
      case of early recurrence in the NSAID group. Both groups had similar length of
      stay with no cases of mortality or major morbidity. CONCLUSIONS: NSAIDs for
      postsurgical pleurodesis pain obviates the need for narcotics without increasing
      the pneumothorax recurrence rate. Prospective randomized controlled studies are
      needed to further investigate this issue.

PMID- 21882032
TI  - Predicting distant metastasis in patients with suspected pancreatic and
      periampullary tumors for selective use of staging laparoscopy.
AB  - BACKGROUND: In patients with pancreatic or periampullary tumor, staging
      laparoscopy (SL) can detect metastases that are occult on computed tomography
      (CT), thereby precluding nontherapeutic laparotomy. Routine SL is not advocated,
      but some studies suggest its selective use. The aim of this study was to identify
      patients at risk for metastasis in whom SL could be beneficial. METHODS: A
      consecutive series of patients who underwent laparotomy for a suspected
      pancreatic or periampullary tumor were analyzed. We included patients with a
      suspected resectable solid lesion and a recent high-quality CT scan. Patients
      with and without an intraoperatively encountered metastasis were compared.
      Regression analysis was performed to examine the association between various
      predictors and metastasis. RESULTS: Data from 385 patients (mean age 63, 41%
      women) were analyzed. Distant metastasis was encountered in 79 patients (21%).
      Logistic regression analysis revealed the following key predictors for
      metastasis: tumor size on CT scan [odds ratio (OR) 1.43, 95% confidence interval
      (CI) 1.16-1.76 per millimeter increase], weight loss (OR 1.28, 95% CI 1.01-1.63
      per doubling the kilograms), and history of jaundice (OR 2.36, 95% CI 0.79-7.06).
      In patients with a tumor >=3 cm and severe weight loss (>=10 kg) and in patients
      with a tumor >=4 cm and moderate weight loss (>=5 kg), the proportion of patients
      with metastasis was >40%. CONCLUSIONS: In patients with a suspected pancreatic or
      periampullary tumor, the tumor size, weight loss, and jaundice are key predictors
      of metastasis at exploration. SL might be beneficial in patients with a tumor >=3
      cm and severe weight loss and in those with a tumor >=4 cm and moderate weight
      loss.

PMID- 21882031
TI  - Ischemic colitis: clinical presentation, localization in relation to risk
      factors, and long-term results.
AB  - BACKGROUND: Ischemic colitis is commonly thought to occur most often in the left
      hemicolon close to the splenic flexure owing to insufficient blood supply near
      Griffith's point. This study investigates the colorectal localization pattern,
      the risk factors, and the long-term outcome of histologically proven ischemic
      colitis. METHODS: Between 1996 and 2004, a total of 49 patients with a median age
      of 69 years (range 26-94 years) with colonoscopically assessed and histologically
      proven ischemic colitis were identified on behalf of the pathology database. Long
      term results of 43 patients were evaluated retrospectively after a median
      interval of 79 months (range 6-163 months). RESULTS: In 27 patients (55%) more
      than one location was affected. We found 98 affected locations in 49 patients.
      The distribution of ischemic colitis in our group shows no significantly
      preferred location. In an exploratory analysis, the cecum, ascending colon, and
      right flexure were affected significantly more often if intake of a nonsteroidal
      antiinflammatory drug (NSAID) is documented. There was no association between the
      location of ischemic colitis and a history of smoking, peripheral artery
      occlusive disease, coronary heart disease, diabetes, or malignant tumor.
      CONCLUSIONS: Ischemic colitis seems not to have a predisposing site of occurrence
      in the colorectum, especially Griffith's point which was not afflicted
      significantly more often than other sites. Frequently, ischemic colitis afflicts
      more than one colonic location. In patients being treated with NSAIDs, ischemic
      colitis was observed significantly more often in the right hemicolon. Recurrence
      of ischemic colitis seems to be rare.

PMID- 21882033
TI  - Catheter fracture of intravenous ports and its management.
AB  - BACKGROUND: Intravenous ports are widely used for oncology patients. However,
      catheter fractures may lead to the need for re-intervention. We aimed to identify
      the risk factors associated with catheter fractures. METHODS: Between January 1
      and December 31, 2006, we retrospectively reviewed the clinical data and plain
      chest films of 1,505 patients implanted with an intravenous port at Chang Gung
      Memorial Hospital. Different vascular sites were compared using the chi-square or
      Fisher's exact test for categorical variables, and the t test was used for
      continuous variables with normal distribution; P < 0.05 was considered
      statistically significant. RESULTS: There were 59 and 1,448 procedures in the
      fracture and non-fracture groups, respectively. Monovariate analysis revealed
      that the risk factors for catheter fracture were as follows: large angle (P <
      0.0001), female gender (P < 0.0008), subclavian route (P < 0.0001), and port type
      Arrow French (Fr.) 8.1 (P < 0.0001). Because these risk factors showed no
      interaction effects, they were all considered independent risk factors. When all
      factors were considered together, all risk factors, except angle and age,
      retained their statistical significance. CONCLUSIONS: Most catheter fractures
      were caused by material weakness. If catheter fracture is confirmed, further
      intervention for port and catheter removal is recommended. Female gender,
      intravenous port implantation via the subclavian route, and the Arrow Fr. 8.1
      port were found to be risk factors. Patients with these risk factors should be
      monitored closely to avoid catheter fractures.

PMID- 21882034
TI  - Intraoperative ultrasound with contrast medium in resective pancreatic surgery: a
      pilot study.
AB  - BACKGROUND: The introduction of contrast-enhanced ultrasound has been a major
      innovation in liver and pancreatic imaging. Previous studies have validated its
      intraoperative use during liver surgery, while there is a lack of data regarding
      its use during pancreatic surgery. The purpose of the present study was to
      prospectively evaluate the possible role of contrast-enhanced intraoperative
      ultrasound (CEIOUS) during resective pancreatic surgery for primary lesion
      characterization and intraoperative staging. MATERIALS AND METHODS: Thirty-four
      patients (70% males, mean age 67.9 years) were selected for pancreatic surgery
      between October 2006 and July 2009. All patients underwent intraoperative
      ultrasound with intravenous injection of 4.8 mL sulfur-hexafluoride microbubbles.
      Location of the primary tumor, relation to the main vessels, contrast medium
      uptake modalities, presence of liver metastases, and multifocal pancreatic
      involvement were evaluated. The majority of operations were
      pancreatoduodenectomies (70.6%) performed for pancreatic ductal adenocarcinoma
      (64.7%). RESULTS: Additional lesions were detected by ultrasound in six patients
      (17.6%: liver metastases in four patients, a hemangioma in one patient, and a
      further pancreatic lesion in one patient). In five of these patients (5/34,
      14.7%) surgical management was modified by these findings. All these new findings
      were diagnosed before injection of contrast medium, except for a metastasis from
      a neuroendocrine tumor; the characterization of the hemangioma was possible only
      after contrast injection. Intraoperative findings regarding location of primary
      tumor, relation to the main vessels, and lesion characterization did not differ
      from those obtained with preoperative imaging. CONCLUSIONS: In our experience
      intraoperative ultrasound is a valid technique for intraoperative staging prior
      to pancreatic resection; it is unclear whether, in pancreatic surgery, the
      addition of contrast enhancement adds any benefit to traditional intraoperative
      ultrasound.

PMID- 21882035
TI  - Management of acute non-cirrhotic and non-malignant portal vein thrombosis: a
      systematic review.
AB  - BACKGROUND: No definitive evidence exists regarding the treatment of acute portal
      vein thrombosis (PVT). Treatment modalities described include conservative
      management, anticoagulation, thrombolysis, and thrombectomy. This review examines
      the impact of such treatment, its outcomes, and the complications resulting from
      the resultant portal hypertension. METHODS: A Medline literature search was
      undertaken using the keywords portal vein thrombosis, anticoagulation,
      thrombolysis, and thrombectomy. The primary end point was portal vein
      recanalization. Secondary outcome measures were morbidity and the development of
      portal hypertension and its sequelae, including variceal bleeding. Data from
      articles relating to PVT in the context of cirrhosis, malignancy, or liver
      transplant were excluded. RESULTS: Early systemic anticoagulation results in
      complete portal vein recanalization in 38.3% of cases and partial recanalization
      in 14.0% of cases. Spontaneous recanalization without treatment can only be
      expected in up to 16.7% of patients. Frequently this is only when associated with
      self-limiting underlying pathology and/or minimal thrombus extension.
      Thrombolysis can be associated with major complications in up to 60% of patients.
      CONCLUSIONS: The natural history of acute PVT is poorly described. Spontaneous
      resolution of acute portal vein thrombosis is uncommon. Early anticoagulation
      results in a satisfactory rate of recanalization with minimal procedure
      associated morbidity. Thrombolysis should be used with caution and only
      considered if the disease is progressive and signs of mesenteric ischemia are
      present. Further well-designed trials with precise outcome reporting are needed
      to improve our understanding of the disease.

PMID- 21882036
TI  - PEP-1-frataxin significantly increases cell proliferation and neuroblast
      differentiation by reducing lipid peroxidation in the mouse dentate gyrus.
AB  - Frataxin plays important roles in the mitochondrial respiratory chain and in the
      differentiation of neurons during early development. In this study, we observed
      the effects of frataxin on cell proliferation and neuroblast differentiation in
      the mouse hippocampal dentate gyrus. For this, we constructed an expression
      vector, PEP-1, that was fused with frataxin to create a PEP-1-frataxin fusion
      protein that easily penetrated frataxin into the blood-brain barrier. Three mg/kg
      PEP-1-frataxin was intraperitoneally administered to mice once a day for 2 weeks.
      The administration of PEP-1 alone did not result in any significant changes in
      the number of Ki67-positive cells and doublecortin (DCX)-immunoreactive
      neuroblasts in the mouse dentate gyrus. However, the administration of PEP-1
      frataxin significantly increased the number of Ki67-positive cells and DCX
      immunoreactive neuroblasts in the mouse dentate gyrus. In addition, PEP-1
      frataxin significantly reduced 4-hydroxynonenal protein levels and
      malondialdehyde formation, while Cu, Zn-superoxide dismutase protein levels were
      maintained. These results suggest that frataxin effectively increased cell
      proliferation and neuroblast differentiation by decreasing lipid peroxidation in
      the dentate gyrus.

PMID- 21882038
TI  - Mitochondrial bioenergetic profile and responses to metabolic inhibition in human
      hepatocarcinoma cell lines with distinct differentiation characteristics.
AB  - The classical view of tumour cell bioenergetics has been recently revised. Then,
      the definition of the mitochondrial profile is considered of fundamental
      importance for the development of anti-cancer therapies, but it still needs to be
      clarified. We investigated two human hepatocellular carcinoma cell lines: the
      partially differentiated HepG2 and the undifferentiated JHH-6. High resolution
      respirometry revealed a marked impairment/uncoupling of OXPHOS in JHH-6 compared
      with HepG2, with the phosphorylation system limiting the capacity for electron
      transport much more in JHH-6. Blocking glycolysis or mitochondrial ATP synthase
      we demonstrated that in JHH-6 ATP synthase functions in reverse and consumes
      glycolytic ATP, thereby sustaining DeltaPsim. A higher expression level of ATP
      synthase Inhibitor Factor 1 (IF1), a higher extent of IF1 bound to ATP synthase
      and a lower ATPase/synthase capacity were documented in JHH-6. Thus, here IF1
      appears to down-regulate the reverse mode of ATPsynthase activity, thereby
      playing a crucial role in controlling energy waste and DeltaPsim. These results,
      while confirming the over-expression of IF1 in cancer cells, are the first to
      indicate an inverse link between cell differentiation status and IF1 (expression
      level and regulatory function).

PMID- 21882040
TI  - Using near real-time morbidity data to identify heat-related illness prevention
      strategies in North Carolina.
AB  - Timely public health interventions reduce heat-related illnesses (HRIs). HRI
      emergency department (ED) visit data provide near real-time morbidity information
      to local and state public health practitioners and may be useful in directing HRI
      prevention efforts. This study examined statewide HRI ED visits in North Carolina
      (NC) from 2008-2010 by age group, month, ED disposition, chief complaint, and
      triage notes. The mean number of HRI ED visits per day was compared to the
      maximum daily temperature. The percentage of HRI ED visits to all ED visits was
      highest in June (0.25%). 15-18 year-olds had the highest percentage of HRI visits
      and were often seen for sports-related heat exposures. Work-related HRI ED visits
      were more common than other causes in 19-45 year-olds. Individuals >=65 years
      were more likely admitted to the hospital than younger individuals. The mean
      daily number of HRI ED visits increased by 1.4 for each 1 degrees F (degree
      Fahrenheit) increase from 90 degrees F to 98 degrees F and by 15.8 for each 1
      degrees F increase from 98 degrees F to 100 degrees F. Results indicate that HRI
      prevention efforts in NC should be emphasized in early summer and targeted to
      adolescents involved in organized sports, young adults with outdoor occupations,
      and seniors. At a maximum daily temperature of 98 degrees F, there was a
      substantial increase in the average daily number of HRI ED visits. ED visit data
      provide timely, sentinel HRI information. Analysis of this near real-time
      morbidity data may assist local and state public health practitioners in
      identification of HRI prevention strategies that are especially relevant to their
      jurisdictions.

PMID- 21882039
TI  - Histologic, immunologic and endocrine biomarkers indicate contaminant effects in
      fishes of the Ashtabula River.
AB  - The use of fish as sentinels of aquatic ecosystem health is a biologically
      relevant approach to environmental monitoring and assessment. We examined the
      health of the Ashtabula River using histologic, immunologic, and endocrine
      biomarkers in brown bullhead (BB; Ameiurus nebulosus) and largemouth bass
      (Micropterus salmoides) and compared fish collected from a reference site
      (Conneaut Creek). Seasonal analysis was necessary to distinguish differences in
      fish between the two rivers. Overall BB from the Ashtabula River had a lower
      condition factor and significantly more macrophage aggregates than those from the
      reference site. Reduced bactericidal and cytotoxic-cell activity was observed in
      anterior kidney leukocytes from both BB and largemouth bass from the Ashtabula
      River. Lower plasma thyroxine and triiodo-L-thyronine in both species in the
      Ashtabula River indicated disruption of the thyroid axis. Differences in
      physiological biomarker responses were supported by body burden chemical
      concentrations when data were analyzed on a seasonal basis. The use of two fish
      species added a level of rigor that demonstrated biological effects were not
      exclusive to a single species. The results provide strong evidence that
      contaminants have affected fish in the Ashtabula River, a Great Lakes Area of
      Concern, and provide a baseline by which to evaluate remediation activities.

PMID- 21882041
TI  - Nitrogen status dependent oxidative stress tolerance conferred by overexpression
      of MnSOD and FeSOD proteins in Anabaena sp. strain PCC7120.
AB  - The heterocystous nitrogen-fixing cyanobacterium, Anabaena sp. strain PCC7120
      displayed two superoxide dismutase (SOD) activities, namely FeSOD and MnSOD.
      Prolonged exposure of Anabaena PCC7120 cells to methyl viologen mediated
      oxidative stress resulted in loss of both SOD activities and induced cell lysis.
      The two SOD proteins were individually overexpressed constitutively in Anabaena
      PCC7120, by genetic manipulation. Under nitrogen-fixing conditions,
      overexpression of MnSOD (sodA) enhanced oxidative stress tolerance, while FeSOD
      (sodB) overexpression was detrimental. Under nitrogen supplemented conditions,
      overexpression of either SOD protein, especially FeSOD, conferred significant
      tolerance against oxidative stress. The results demonstrate a nitrogen status
      dependent protective role of individual superoxide dismutases in Anabaena PCC7120
      during oxidative stress.

PMID- 21882037
TI  - Mammalian NADH:ubiquinone oxidoreductase (Complex I) and nicotinamide nucleotide
      transhydrogenase (Nnt) together regulate the mitochondrial production of H2O2-
      implications for their role in disease, especially cancer.
AB  - Mammalian NADH:ubiquinone oxidoreductase (Complex I) in the mitochondrial inner
      membrane catalyzes the oxidation of NADH in the matrix. Excess NADH reduces nine
      of the ten prosthetic groups of the enzyme in bovine-heart submitochondrial
      particles with a rate of at least 3,300 s-1. This results in an overall NADH->O2
      rate of ca. 150 s-1. It has long been known that the bovine enzyme also has a
      specific reaction site for NADPH. At neutral pH excess NADPH reduces only three
      to four of the prosthetic groups in Complex I with a rate of 40 s-1 at 22 
      degrees C. The reducing equivalents remain essentially locked in the enzyme
      because the overall NADPH->O2 rate (1.4 s-1) is negligible. The physiological
      significance of the reaction with NADPH is still unclear. A number of recent
      developments has revived our thinking about this enigma. We hypothesize that
      Complex I and the Deltap-driven nicotinamide nucleotide transhydrogenase (Nnt) co
      operate in an energy-dependent attenuation of the hydrogen-peroxide generation by
      Complex I. This co-operation is thought to be mediated by the NADPH/NADP+ ratio
      in the vicinity of the NADPH site of Complex I. It is proposed that the specific
      H2O2 production by Complex I, and the attenuation of it, is of importance for
      apoptosis, autophagy and the survival mechanism of a number of cancers.
      Verification of this hypothesis may contribute to a better understanding of the
      regulation of these processes.

PMID- 21882042
TI  - Genome wide gene expression in artificially synthesized amphidiploids of
      Arabidopsis.
AB  - The merging of two different genomes occurs during the formation of
      amphidiploids, and the merged regulatory networks have the potential to generate
      a new gene expression pattern. We examined the genome-wide gene expression of two
      newly synthesized amphidiploids between Arabidopsis thaliana and the related
      species Arabidopsis lyrata subsp. lyrata and Arabidopsis halleri subsp.
      gemmifera. 1,137 (4.7%) and 1,316 (5.4%) of probesets showed differential gene
      expression in A. thaliana-A. halleri and A. thaliana-A. lyrata hybrids
      respectively, compared to the mid parent value and of these, 489 were in common.
      Genes that differed in expression between the parental lines tended to have an
      expression level in both hybrids differing from the mid parent value. In contrast
      to protein coding genes, there is little differential expression of transposons.
      Genes in the categories of chloroplast-targeted and response to stress were
      overrepresented in the non-additively expressed genes in both amphidiploids. As
      these genes have the potential to contribute directly to the plant phenotype, we
      suggest that rapid changes of gene expression in amphidiploids might be important
      for producing greater biomass.

PMID- 21882043
TI  - Kobe earthquake and post-traumatic stress in school-aged children.
AB  - BACKGROUND: The psychological reactions to catastrophic events are not known well
      in children. PURPOSE: The present study was performed to quantify the core
      features of post-traumatic stress reactions in schoolchildren after the Kobe
      earthquake. METHODS: Children's psychological reactions to the Kobe earthquake
      were examined in a total of 8,800 schoolchildren attending the third, fifth, or
      eighth grade in the disaster areas. The control subjects were 1,886
      schoolchildren in the same grades in distant areas minimally affected by the
      earthquake. A self-report questionnaire was developed with reference to the
      Diagnostic and Statistical Manual of Mental Disorders-IV and the post-traumatic
      stress disorder reaction index and was used to score psychological reactions
      rating them from 1 to 4 depending on the frequency of the symptom. The survey was
      conducted four times, from 4 months to 2 years after the earthquake. RESULTS:
      Three factors were consistently extracted by factor analysis on the results of
      each study. Factor 1 was interpreted as relating to direct fear of the disaster
      and general anxiety, factor 2 as relating to depression and physical symptoms,
      and factor 3 as social responsibility such as feelings of sympathy for those who
      are suffering more severely and guilt for surviving. Young schoolchildren
      displayed particularly high scores on these factors. Furthermore, these factors
      were significantly associated with injuries of the children themselves,
      fatalities/injuries of family members, and the experience of being rescued or
      staying in shelters. CONCLUSIONS: Psychological and comprehensive interventions
      should be directed at the most vulnerable populations of young children after
      future earthquakes.

PMID- 21882044
TI  - Nucleotide polymorphisms in the canine Noggin gene and their distribution among
      dog (Canis lupus familiaris) breeds.
AB  - Noggin (NOG) is an important regulator for the signaling of bone morphogenetic
      proteins. In this study, we sequenced the complete coding sequence of the canine
      NOG gene and characterized the nucleotide polymorphisms. The sequence length
      varied from 717 to 729 bp, depending on the number of a 6-bp tandem repeat unit
      (GGCGCG), an insertion that has not been observed in other mammalian NOG genes
      investigated to date. It results in extensions of (Gly-Ala)3-5 in the putative
      NOG protein. To survey the distribution of these tandem repeat polymorphisms, we
      analyzed 126 individuals in seven dog breeds. We identified only three alleles:
      (GGCGCG)3, (GGCGCG)4, and (GGCGCG)5. Although the allele frequencies were
      remarkably different among the breeds, the three alleles were present in all
      seven of the breeds and did not show any deviation from Hardy-Weinberg
      equilibrium.

PMID- 21882045
TI  - Laparoscopic management of impalpable testes: comparison of different techniques.
AB  - PURPOSE: Laparoscopy is an important modality for management of impalpable
      testes. We present long-term outcomes of intra-abdominal testes managed by either
      single stage orchidopexy or two-stage Fowler Stephen's orchidopexy (FSO) over 12
      years. METHODS: Data were prospectively collected and retrospectively analyzed on
      patients who underwent laparoscopy for impalpable testes between 1998 and 2010.
      Demographic data, intra-operative findings, management, histology and follow-up
      findings were collected and analyzed. Fisher's Exact test was used for
      statistical analysis. RESULTS: Laparoscopy was performed for 168 impalpable
      testes (78 left, 58 right and 16 bilateral). Patients were between 8 months and
      15 years of age (median 1 year 10 months). Ninety-three testes were found to have
      cord structures entering the inguinal ring (canalicular), 65 were intra-abdominal
      and 10 had blind ending vas and/or vessel. Fifty-seven (34%) testes were atrophic
      and underwent orchidectomy; 100 (60%) testes underwent orchidopexy: either two
      stage FSO (48) or single stage orchidopexy (52) and 10 (7%) had findings
      consistent with 'vanishing testes'. Histopathologically, the excised remnants
      (34%) showed no viable testicular tissue. The follow-up was a median of 8 months
      (3 months to 6 years). Four patients were lost to follow-up (two each after FSO
      and single stage orchidopexy) while, two FSO are awaiting follow-up. At follow
      up, 36/44 testes (FSO) and 13/13 testes (single stage orchidopexy) are in the
      scrotum and of good size. Eight testes had atrophied after two-staged FSO.
      CONCLUSION: Canalicular testes are often difficult to palpate (55%). Laparoscopy
      allows direct visualization and definitive management. There is no statistically
      significant difference between the results following single stage orchidopexy or
      two-stage FSO for impalpable testes.

PMID- 21882046
TI  - Analysis of the protective potential of antigens released by Leishmania (Viannia)
      shawi promastigotes.
AB  - Leishmania (Viannia) shawi causes cutaneous lesions in humans. Parasite antigens
      conferring significant protection against American tegumentar leishmaniosis (ATL)
      might be important for the development of effective vaccine. Therefore, this work
      evaluates the protective effect of antigenic fractions released by L. shawi.
      Antigens released by promastigotes to culture medium were concentrated and
      isolated by SDS-PAGE. The three main fractions LsPass1 (>75 kDa), LsPass2 (75-50
      kDa) and LsPass3 (<50 kDa) were electro-eluted according with their molecular
      mass. Immunized BALB/c mice were challenged with L. shawi promastigotes and the
      course of infection monitored during 5 weeks. LsPass1-challenged mice showed no
      protection, however, a strong degree of protection associated to smaller lesions
      and high expression of IFN-gamma and TNF-alpha by CD4(+) T, CD8(+) T and double
      negative CD4CD8 cells was achieved in LsPass3-challenged mice. Furthermore,
      LsPass2-challenged mice showed an intermediated degree of protection associated
      to high levels of IFN-gamma, IL-4 and IL-10 mRNA. In spite of increased
      expression of IFN-gamma and TNF-alpha, high amounts of IL-4 and IL-10 mRNA were
      also detected in LsPass3-challenged mice indicating a possible contribution of
      these cytokines for the persistence of a residual number of parasites that may be
      important in inducing long-lasting immunity. Therefore, LsPass3 seems to be an
      interesting alternative that should be considered in the development of an
      effective vaccine against ATL.

PMID- 21882047
TI  - Identification of CD44+CD24+ gastric cancer stem cells.
AB  - OBJECTIVE: Purification and characterization of cancer stem cells (CSCs) can lead
      to the identification of targets for therapeutic interventions of cancer. With
      regard to gastric cancer, studies have not yet defined and characterized CSCs.
      METHODS: The expression of the cell surface markers CD44 and CD24 was examined in
      gastric cell lines AGS and gastric cancer tissues from five patients with
      fluorescence-activated cell sorting analysis (FACS). The tumorigenic properties,
      self-renewal, and differentiated progeny in the two distinct cell populations
      CD44+CD24+ and CD44-CD24- were identified in vivo serial transplantation and in
      vitro culture. Real-time RT-PCR was used to assess the expression of sonic
      hedgehog (SHH), patched 1 (PTCH1), and GLI3 signaling molecules in CD44+CD24+ and
      CD44-CD24- cells. RESULTS: As few as 200 CD44+CD24+ cells injected in NOD-SCID
      mice were able to generate tumors in 50% of mice (6 of 12), while tumors did not
      form in mice until at least 10,000 CD44-CD24- cells were injected, where only one
      of 12 mice formed a tumor, further verifying that CD44+CD24+ gastric cancer cells
      have the capacity to both self-renew and produce differentiated progeny.
      Moreover, SHH, PTCH1, and GLI3 mRNA expression increased significantly in the
      CD44+CD24+ subpopulation when compared with the CD44-CD24- subpopulation.
      CONCLUSIONS: These studies strongly suggest that the CD44+CD24+ subpopulation of
      human gastric cancer cell lines, AGS, is gastric cancer stem cells.

PMID- 21882048
TI  - ID4 is frequently downregulated and partially hypermethylated in prostate cancer.
AB  - PURPOSE: The candidate tumor suppressor ID4 is downregulated in various cancers
      by DNA hypermethylation. We have performed the first systematic analysis of ID4
      expression and methylation in prostate cancer. METHODS: ID4 mRNA expression was
      analyzed by quantitative RT-PCR in 47 carcinoma and 13 benign prostatic tissues
      obtained by prostatectomy. Methylation was analyzed in an extended series of
      samples by methylation-specific MS-PCR and pyrosequencing, controlled by
      bisulfite sequencing. RESULTS: ID4 expression was significantly decreased in
      prostate cancers, especially in cases with adverse clinical and histopathological
      features and earlier recurrence. Hypermethylation in carcinomas was detected by
      MS-PCR and pyrosequencing, but the results of the two techniques were not fully
      concordant. The difference was created by generally partial and heterogeneous
      methylation. Weak methylation was also detected in benign prostatic tissue
      samples. CONCLUSIONS: ID4 downregulation may contribute to prostate cancer
      pathogenesis and is often accompanied by DNA hypermethylation. The case of ID4
      illustrates exemplarily the limits and pitfalls of techniques for the detection
      of methylation changes in prostate cancer tissues.

PMID- 21882049
TI  - Effect of chemical chaperones on glucose-induced lysozyme modifications.
AB  - Nonenzymatic glycation of biomacromolecules occurs due to the diabetes mellitus
      and ageing. A number of small molecules, known as chemical chaperones, stabilize
      protein conformation against thermal and chemically induced denaturation. These
      compounds are including: polyamines (e.g. spermine and spermidine), amino acids
      (e.g. lysine) and polyols (e.g. glycerol). In this study the effect of spermidine
      (Spd), spermine (Spm), and glycerol on glycation, structure and function of
      lysozyme (LZ), as an extra-cellular protein, by different techniques is
      investigated. LZ is incubated with or without glucose (50 or 100 mM) in the
      absence or presence of Spd/Spm/glycerol at 37  degrees C up to 16 weeks. All the
      observed changes of glycated-LZ in comparison with the native protein, including:
      increased fluorescence emission, alteration in the secondary and tertiary
      structure, and reduced electrophoretic mobility- indicate its structural changes
      that are accompanied with its reduced activity. Glucose in the presence or
      absence of Spd induces the protein dimerization, but glucose plus Spm induces its
      trimmerization. In contrast, glycerol inhibits the LZ glycation and prevents the
      large changes on its structure and function. Glucose binds lysine residues,
      decreases the protein positive charges and induces some alterations in its
      structure and activity. Polyamines also directly bind to LZ, increase its
      positive charges and hence induce more glycation; more conformational changes,
      oligomerization and its inactivation in the presence of glucose, but glycerol
      affect the protein environment and preserve protein from these harmful effects.

PMID- 21882050
TI  - CHO proteome alterations induced by reverse transformation.

PMID- 21882051
TI  - Alleviation of salt stress in lemongrass by salicylic acid.
AB  - Soil salinity is one of the key factors adversely affecting the growth, yield,
      and quality of crops. A pot study was conducted to find out whether exogenous
      application of salicylic acid could ameliorate the adverse effect of salinity in
      lemongrass (Cymbopogon flexuosus Steud. Wats.). Two Cymbopogon varieties, Krishna
      and Neema, were used in the study. Three salinity levels, viz, 50, 100, and 150
      mM of NaCl, were applied to 30-day-old plants. Salicylic acid (SA) was applied as
      foliar spray at 10(-5) M concentration. Totally, six SA-sprays were carried out
      at 10-day intervals, following the first spray at 30 days after sowing. The
      growth parameters were progressively reduced with the increase in salinity level;
      however, growth inhibition was significantly reduced by the foliar application of
      SA. With the increase in salt stress, a gradual decrease in the activities of
      carbonic anhydrase and nitrate reductase was observed in both the varieties. SA
      treatment not only ameliorated the adverse effects of NaCl but also showed a
      significant improvement in the activities of these enzymes compared with the
      untreated stressed-plants. The plants supplemented with NaCl exhibited a
      significant increase in electrolyte leakage, proline content, and phosphoenol
      pyruvate carboxylase activity. Content and yield of essential oil was also
      significantly decreased in plants that received salinity levels; however, SA
      overcame the unfavorable effects of salinity stress to a considerable extent.
      Lemongrass variety Krishna was found to be more adapted to salt stress than
      Neema, as indicated by the overall performance of the two varieties under salt
      conditions.

PMID- 21882052
TI  - Is there a role for clinical practice guidelines in multidisciplinary tumor board
      meetings? A descriptive study of knowledge transfer between research and
      practice.
AB  - The aim of this study was to characterize practice patterns and decision-making
      processes of healthcare providers attending weekly neuro-oncology tumor board
      meetings, and to assess their familiarity with clinical practice guidelines
      (CPGs) in neuro-oncology. Members of the Neuro-Oncology Tumor Team at two
      tertiary cancer centers completed a web-based questionnaire assessing
      characteristics of weekly tumor board meetings and perceptions of CPGs. Twenty
      three (66%) tumor team members responded. Diagnostic imaging results and
      interpretation, medical, surgical, and/or radiation treatment planning, and
      pathology results and interpretation were the most commonly identified aspects of
      patient care discussed at tumor board meetings, and almost all respondents
      indicated that these meetings were "very beneficial" to their own practice. When
      deciding on a treatment plan, respondents rely most on the clinical expertise of
      colleagues, medical literature, personal experience, active clinical trial
      protocols, and published CPGs. Opinions of the local CPGs varied considerably,
      and while 56% of respondents supported regular discussion of them during
      meetings, only 32% indicated that they were routinely reviewed. Updating the
      literature more frequently, implementing a formal grading system for the
      evidence, and incorporating clinical care pathways were the most frequently cited
      methods to improve the CPGs. Tumor board meetings are beneficial to the treatment
      planning process for neuro-oncology patients.

PMID- 21882053
TI  - Sociosexuality predicts women's preferences for symmetry in men's faces.
AB  - Although men displaying cues of good physical condition possess traits that are
      desirable in a mate (e.g., good health), these men are also more likely to
      possess antisocial characteristics that are undesirable in a long-term partner
      (e.g., aggression and tendency to infidelity). How women resolve this trade-off
      between the costs and benefits associated with choosing a mate in good physical
      condition may lead to strategic variation in women's mate preferences. Because
      the costs of choosing a mate with antisocial personality characteristics are
      greater in long- than short-term relationships, women's sociosexuality (i.e., the
      extent to which they are interested in uncommitted sexual relationships) may
      predict individual differences in their mate preferences. Here we investigated
      variation in 99 heterosexual women's preferences for facial symmetry, a
      characteristic that is thought to be an important cue of physical condition.
      Symmetry preferences were assessed using pairs of symmetrized and original (i.e.,
      relatively asymmetric) versions of 10 male and 10 female faces. Analyses showed
      that women's sociosexuality, and their sociosexual attitude in particular,
      predicted their preferences for symmetry in men's, but not women's, faces; women
      who reported being more interested in short-term, uncommitted relationships
      demonstrated stronger attraction to symmetric men. Our findings present new
      evidence for potentially adaptive variation in women's symmetry preferences that
      is consistent with trade-off theories of attraction.

PMID- 21882054
TI  - Condom use errors and problems in a national sample of young Croatian adults.
AB  - In this study, we examined the correlates of condom use errors and problems in a
      population-based study conducted in 2010 among young Croatian adults aged 18-25
      years. Out of a total sample of 1,005 participants, 679 reported condom use in
      the preceding year. The analyses focused on four outcomes: condom breakage,
      condom slippage, condom-related erection loss, and delayed condom application.
      Eighteen percent of participants experienced breakage, 13% reported slippage, 17%
      reported erection loss, and 34% applied a condom after intercourse started.
      Multivariate logistic regression analyses were performed to examine the
      correlates of these condom use errors and problems. Condom breakage was less
      likely to be reported by women and older participants. The odds of breakage were
      increased for participants who reported being under the influence of drugs during
      sex and who reported other condom use errors and problems in the past year.
      Condom slippage was more likely to occur among younger participants and those who
      reported condom breakage and delayed condom application. Condom-related erection
      loss was positively associated with a higher number of sexual partners in the
      preceding year, condom breakage, and a higher score on the Anti-Erotic Obstacles
      to Condom Use Scale. Odds of delayed condom application were increased for
      participants who experienced condom breakage and for those who consumed alcohol
      before sex in the past year. Having used a condom at first sex significantly
      reduced the odds of applying a condom after intercourse started. In comparison to
      non-habitual condom users, habitual users were found less likely to report any of
      the assessed condom use errors and problems. Improving condom use skills remains
      an important task in Croatia, which is currently hampered by the absence of
      evidence-based sex education in schools.

PMID- 21882055
TI  - Solastalgia and the gendered nature of climate change: an example from Erub
      Island, Torres Strait.
AB  - This communication focuses on respected older womens' ('Aunties') experiences of
      climate and other environmental change observed on Australia's Erub Island in the
      Torres Strait. By documenting these experiences, we explore the gendered nature
      of climate change, and provide new perspectives on how these environmental
      impacts are experienced, enacted and responded to. The way these adverse changes
      affect people and places is bound up with numerous constructions of difference,
      including gender. The responses of the Aunties interviewed to climate change
      impacts revealed Solastalgia; feelings of sadness, worry, fear and distress,
      along with a declining sense of self, belonging and familiarity.

PMID- 21882056
TI  - Phenytoin, levetiracetam, and pregabalin in the acute management of refractory
      status epilepticus in patients with brain tumors.
AB  - BACKGROUND: There were nearly 700,000 patients in the United States in 2010
      living with brain tumor diagnoses. The incidence of seizures in this population
      is as high as 70% and is historically difficult to control. Approximately 30-40%
      of brain tumors patients who present with status epilepticus (SE) will not
      respond to typical therapy consisting of benzodiazepines and phenytoin (PHT),
      resulting in patients with refractory status epilepticus (RSE). RSE is usually
      treated with anesthetic doses of propofol or midazolam infusions. This therapy
      can have significant risk, particularly in patients with cancer. METHODS: A
      retrospective chart review was performed on 23 patients with primary or
      metastatic brain tumors whose SE was treated with intravenous PHT, levetiracetam
      (LEV), and oral pregabalin (PGB). RESULTS: In all the patients under study, PHT
      or LEV was used as first-line therapy. PGB was typically used as third-line
      treatment. The median daily dose of PGB was 375 mg (usually divided BID or TID),
      and the median daily dose of LEV 3000 mg (usually divided BID). Cessation of SE
      was seen in 16/23 (70%) after administration of PHT, LEV, and PGB. SE was
      aborted, on average, 24 h after addition of the third antiepileptic drug. Only
      one patient in the responder group required intubation. Mortality rate was zero
      in the responder group. No adverse reactions to this medication regimen were
      observed. CONCLUSION: Our study suggests that the administration of PHT, LEV, and
      PGB in brain tumor patients with RSE is safe and highly effective.

PMID- 21882057
TI  - Religious orientation and health among active older adults in the United States.
AB  - This study utilizes a combination of intrinsic and extrinsic Religious
      Orientation Scales to explore the connection between religion and health in a
      sample of physically active, older adults. The revised Religious Orientation
      Scale and the RAND Short Form 36 (SF-36) were adopted to relate religious
      orientation (intrinsic, extrinsic, pro-religious, and non-religious) and self
      rated mental and physical health status. Individuals of pro-religious orientation
      reported significantly worse health for physical functioning, role limitations
      due to physical health, and energy or fatigue when compared with those of all
      other religious orientations; however, no dose-response relationships were found
      between religious orientation and self-rated health. The results of this study
      indicate that deleterious health effects may accompany pro-religious orientation.
      Caution is provided for directors of religious programs for older adults. 

PMID- 21882058
TI  - [Unruptured intracranial aneurysms].
AB  - The incidental discovery of an asymptomatic intracranial arterial aneurysm is no
      longer uncommon. It can change a person's life. Decision-making should be guided
      by a thorough comparison of the risks associated with the natural course and with
      microsurgical or endovascular intervention. At present this comparison will favor
      a conservative approach in the majority of patients, especially in those with
      small aneurysms or who are over 50 years old.

PMID- 21882059
TI  - [Cerebral hemiatrophy without serious psychopathological symptoms].

PMID- 21882060
TI  - [Quality features of German memory clinics: a cross-sectional study].
AB  - BACKGROUND: Although memory clinics have become an established institution for
      diagnosing and treating dementia in Germany over the years, little is known about
      their quality features. Considering the increasing societal relevance of
      dementia, memory clinics will most likely gain in importance in the future.
      MATERIAL AND METHODS: Addresses of German memory clinics were obtained by an
      online search. All institutions were surveyed via questionnaire with items
      regarding structural characteristics (designation, affiliation, services offered,
      funding) and quality features (waiting times, disease severity at diagnosis).
      RESULTS: The results of the inquiry of all institutions (n=153, response: 48%)
      show memory clinics as specialised institutions that have a low degree of
      standardisation, but basically have a high structural quality for diagnostic and
      therapeutic care. CONCLUSION: The development of homogeneous structure and
      process standards could help to establish memory clinics in regular care and to
      establish sustainable funding. In order to achieve this, an even more intensive
      collaboration and consensus building of all German memory clinics would be needed
      as well as a coordinated representation of interests.

PMID- 21882061
TI  - Iterative generation of diagnostic categories through production and practice:
      the case of postpartum depression.
AB  - Examining the process undertaken to name and codify psychiatric illnesses
      provides important insights into how everyday healthcare practices are shaped by
      knowledge production processes. However, studies of illness classification often
      rely on an overly simplified distinction between the production of diagnostic
      categories and the application of those categories in practice. Drawing insight
      from science and technology studies, I argue that psychiatric diagnostic
      categories are iteratively generated through production and practice, even during
      the development of those categories. Through a discursive analysis of interviews,
      archival documents, and psychiatric literature, I identify the practical politics
      that enabled the creation of the postpartum depression (PPD) modifier in the
      Diagnostic and Statistical Manual of Mental Disorders, version four (DSM-IV). In
      addition, I demonstrate how the overarching discourses of evidence-based decision
      making and biomedicine shaped the development of the postpartum modifier, and
      draw together comments made by interview participants regarding the
      administrative value of a PPD-related category in the DSM. These remarks suggest
      that, in their practice, researchers and clinicians also take into consideration
      their own knowledge about DSM production processes, providing further support for
      the argument that diagnostic categories are iteratively generated.

PMID- 21882063
TI  - Care experience-based methodologies: performance improvement roadmap to value
      driven health care.
AB  - BACKGROUND: The literature contains proposals for creating value by creating
      exceptional patient experiences rather than simply improving services. However,
      few articles describe replicable applications focused on the patient experience.
      QUESTIONS/PURPOSES: We (1) describe the refinement and exportation of an approach
      that focuses on the patient and family experience; and (2) report changes in
      patient satisfaction, infection rates, length of stay, mortality rates, clinical
      indicators, staff turnover, and cost. METHODS: The Patient and Family-Centered
      Care Methodology and Practice (PFCC M/P) is a six-step process: (1) selecting a
      care experience needing improvement; (2) establishing a guiding council; (3)
      evaluating the current state; (4) developing a permanent working group; (5)
      creating a shared vision of the ideal experience; and (6) identifying improvement
      projects to address the gap between the current and ideal experience. We assessed
      patient satisfaction, changes in clinical indicators, staff turnover, and cost in
      three clinical programs. RESULTS: In TJA, patient satisfaction is at the 99th
      percentile; length of stay, infection rates, and mortality rates are
      substantially better than the national average. In trauma, patient satisfaction
      increased, time in cervical collars decreased, staff turnover decreased, and the
      incidence of lost patient belongings was eliminated. In orthopaedic spine,
      patient satisfaction is higher than the national average, average time for
      transfer to bed decreased (%), length of stay decreased, and average discharge
      time decreased. Each of these would have a positive impact on cost. CONCLUSIONS:
      PFCC M/P offers a road map for redefining value as what is important to patients
      and families.

PMID- 21882062
TI  - Transcriptomes of the major human pancreatic cell types.
AB  - AIMS/HYPOTHESIS: We sought to determine the mRNA transcriptome of all major human
      pancreatic endocrine and exocrine cell subtypes, including human alpha, beta,
      duct and acinar cells. In addition, we identified the cell type-specific
      distribution of transcription factors, signalling ligands and their receptors.
      METHODS: Islet samples from healthy human donors were enzymatically dispersed to
      single cells and labelled with cell type-specific surface-reactive antibodies.
      Live endocrine and exocrine cell subpopulations were isolated by FACS and gene
      expression analyses were performed using microarray analysis and quantitative RT
      PCR. Computational tools were used to evaluate receptor-ligand representation in
      these populations. RESULTS: Analysis of the transcriptomes of alpha, beta, large
      duct, small duct and acinar cells revealed previously unrecognised gene
      expression patterns in these cell types, including transcriptional regulators
      HOPX and HDAC9 in the human beta cell population. The abundance of some
      regulatory proteins was different from that reported in mouse tissue. For
      example, v-maf musculoaponeurotic fibrosarcoma oncogene homologue B (avian)
      (MAFB) was detected at equal levels in adult human alpha and beta cells, but is
      absent from adult mouse beta cells. Analysis of ligand-receptor interactions
      suggested that EPH receptor-ephrin communication between exocrine and endocrine
      cells contributes to pancreatic function. CONCLUSIONS/INTERPRETATION: This is the
      first comprehensive analysis of the transcriptomes of human exocrine and
      endocrine pancreatic cell types-including beta cells-and provides a useful
      resource for diabetes research. In addition, paracrine signalling pathways within
      the pancreas are shown. These results will help guide efforts to specify human
      beta cell fate by embryonic stem cell or induced pluripotent stem cell
      differentiation or genetic reprogramming.

PMID- 21882064
TI  - Higher expression of myosin heavy chain IIx in wrist flexors in cerebral palsy.
AB  - BACKGROUND: Children with cerebral palsy (CP) use their paretic arm less than
      normal but have a relative overactivity of wrist flexors, causing an impairing
      flexed position of the wrist. Voluntary use of a muscle downregulates myosin
      heavy chain (MyHC) IIx, but it is unclear whether the relative overactivity of
      wrist flexors and extensors in children with CP affects MyHC expression compared
      to normal subjects. QUESTIONS/PURPOSES: We therefore asked whether MyHC
      expression composition differs in wrist flexors compared to extensors in children
      with CP and in controls and whether it is related to clinical findings. METHODS:
      We took muscle biopsies from wrist flexors and extensors during hand surgery in
      children with CP (n = 9) and during open reduction of forearm fractures in
      control children (n = 5). The expression of the MyHC I, IIa, and IIx isoforms
      were determined on silver-stained 6% SDS-PAGE. RESULTS: CP flexors showed a
      higher proportion of MyHC IIx (40%) than control flexors (16%) and CP extensors
      (20%). MyHC IIa isoform proportion was lower in CP flexors (27%) than in control
      flexors (46%) and in CP extensors (45%). MyHC I expression was lower in CP (36%)
      than in controls (46%) for wrist extensors only. CONCLUSIONS: Both the brain
      injury in CP and the different demands on flexors and extensors affect the
      expression of MyHCs. The higher amount of MyHC IIx in CP could be caused by a
      decreased voluntary use of the hemiplegic arm. CLINICAL RELEVANCE: More
      information on the structural difference between flexors and extensors in normal
      and spastic muscle could improve the understanding of strain of wrist extensors
      and possibly the development of flexion contractures in CP.

PMID- 21882066
TI  - Trace elements in fingernails of healthy Chinese centenarians.
AB  - Trace element concentrations in body tissues of healthy centenarians have not
      been widely analyzed, yet they can be used as reference data leading to improved
      assessment of the aging process and monitoring of the micronutrient status of
      this age group. The present study sought to assess trace element concentrations
      and behaviors in the fingernails of healthy Chinese centenarians. The effects of
      gender on element concentrations, which also play an important role in
      determining the lifespan, were also investigated. Trace elements (Ba, Cd, Co, Cr,
      Cu, Fe, Li, Mn, Mo, Ni, Pb, Se, Sr, and Zn) in the fingernails of 78 healthy
      Chinese centenarians were determined by inductively coupled plasma mass
      spectrometry. The overall reference values obtained in milligram per kilogram are
      as follows: Ba, 5.10; Cd, 0.031; Co, 0.101; Cr, 0.82; Cu, 3.71; Fe, 154.35; Li,
      0.31; Mn, 3.09; Mo, 0.040; Ni, 0.95; Pb, 1.86; Se, 0.44; Sr, 6.20; and Zn,
      147.96. Data analysis showed that only Cr and Se concentrations show a normal
      distribution, and no significant difference between male and female groups was
      found for any element except Cr. Result also revealed that sufficient Se, Co, and
      Zn as well as lower or lack of exposure to Cr contribute positively to the
      lifespan of centenarians. The results suggest that regulating in vivo contents of
      trace elements, especially Se, Co, and Zn, is reasonable to intervene with
      geriatric diseases.

PMID- 21882065
TI  - Changes in small intestinal morphology and digestive enzyme activity with oral
      administration of copper-loaded chitosan nanoparticles in rats.
AB  - The experiment was conducted to evaluate the effect of copper-loaded chitosan
      nanoparticles on the small intestinal morphology and activities of digestive
      enzyme and mucosal disaccharase in rats. Forty male Sprague-Dawley rats, with
      average body weight of 82 g, were randomly allotted to five groups (n = 8). All
      rats were received a basal diet (control) or the same basal diet added with 80
      mg/kg BW CuSO(4), 80 mg/kg BW chitosan (CS-I), 80 mg/kg BW copper-loaded chitosan
      nanoparticles (CSN-I), 160 mg/kg BW copper-loaded chitosan nanoparticles (CSN
      II), respectively. The experiment lasted 21 days. The results showed that the
      villus heights of the small intestinal mucosa in groups CSN-I and CSN-II were
      higher than those of the control, group CuSO(4) or CS-I. The crypt depth of
      duodenum and ileum mucosa in group CSN-I or CSN-II was depressed. Compared with
      the control, there were no significant effects of CuSO(4) or CS-I on the villus
      height and crypt depth of small intestinal mucosa. Supplementation with CSN
      improved the activities of trypsin, amylase and lipase in the small intestinal
      contents and maltase, sucrase and lactase of duodenum, jejunum, and ileum mucosa
      while there were no significant effects of CuSO(4) on the digestive enzyme
      activities of the small content compared with the control. The results indicated
      that intestinal morphology, activities of digestive enzyme in digesta and mucosal
      disaccharase were beneficially changed by treatment of copper-loaded chitosan
      nanoparticles.

PMID- 21882067
TI  - Effects of oxidized cooking oil and alpha-lipoic acid on blood antioxidants:
      enzyme activities and lipid peroxidation in rats fed a high-fat diet.
AB  - The effects of administration of oxidized rapeseed oil and alpha-lipoic acid on
      activities of blood antioxidant enzymes and malondialdehyde (MDA) concentration
      were studied in laboratory rats fed a high-fat diet. Addition of oxidized oil
      resulted in increased production of oxygen radicals, evidenced by elevated plasma
      MDA production. Such effect was counteracted by administration of alpha-lipoic
      acid. There was an increase of the activities of superoxide dismutase (total and
      Cu/Zn-SOD) and catalase in rats fed a high-fat diet to which 10% oxidized oil was
      added. Administration of alpha-lipoic acid resulted in a decrease of the
      activities of these enzymes.

PMID- 21882068
TI  - Dietary high vanadium causes oxidative damage-induced renal and hepatic toxicity
      in broilers.
AB  - The purpose of this study was to investigate the renal and hepatic oxidative
      damage and toxicity caused by dietary high vanadium in broilers. A total of 420
      one-day-old avian broilers were divided into six groups and fed on a corn-soybean
      basal diet as control diet (vanadium 0.073 mg/kg), and five high vanadium diets
      (vanadium 5 mg/kg, high vanadium group I; 15 mg/kg, high vanadium group II; 30
      mg/kg, high vanadium group III; 45 mg/kg, high vanadium group IV; and 60 mg/kg,
      high vanadium group V) throughout the experimental period of 42 days. The results
      showed that the renal and hepatic superoxide dismutase (SOD) and glutathione
      peroxidase (GSH-Px) activities, ability to inhibit hydroxy radical, and
      malondialdehyde (MDA), glutathione, and vanadium contents were not significantly
      changed in high vanadium group I and II when compared with those of the control
      groups. However, the SOD and GSH-Px activities, ability to inhibit hydroxy
      radical, and GSH content were significantly decreased, and the MDA and vanadium
      contents were markedly increased in high vanadium groups III, IV, and V. At the
      same time, the lesions were also observed in the kidney and liver of high
      vanadium groups III, IV, and V. The renal tubular epithelial cells showed
      granular degeneration and vacuolar degeneration, and hepatocytes showed granular
      degeneration, vacuolar degeneration, and fatty degeneration. It was concluded
      that dietary vanadium in the range of 30-60 mg/kg could cause oxidative damage
      and vanadium accumulation, which induced renal and hepatic toxicity and lesions.
      The renal and hepatic function was finally impaired in boilers.

PMID- 21882069
TI  - Relationships between respiratory function disorders and serum copper levels in
      copper mineworkers.
AB  - The aim of this study was to investigate the respiratory function disorders that
      could be related to dust exposure during the production of copper mine in copper
      mineworkers (CMWs). The study included 75 male CMWs (mean age, 32.0 +/- 7.1
      years, 58.6% smokers) and 75 male age- and smoking status-matched healthy control
      subjects. Serum Cu level was significantly higher in the CMW group (0.80 +/- 0.62
      MUg/ml) than the control group (0.60 +/- 0.39 MUg/ml) (p = 0.017). Significant
      negative correlations were found between serum Cu level and forced expiratory
      volume in first second (r = -0.600; p < 0.001) and between serum Cu level and
      forced vital capacity (r = -0.593; p = <0.001) in CMWs. Serum Cu level was
      significantly higher in the restrictive type pulmonary function disorders group
      (1.36 +/- 0.62 MUg/ml) than obstructive type (0.90 +/- 0.55 MUg/ml) and normal
      pulmonary function pattern group (0.53 +/- 0.43 MUg/ml) (p < 0.001). Patients
      with radiological parenchymal abnormalities had significantly higher serum copper
      levels than those without abnormalities (1.53 +/- 0.52 vs. 0.71 +/- 0.52 MUg/ml,
      respectively; p = 0.002). In conclusion, result of the study has shown a negative
      association between pulmonary functions disorders and radiological abnormalities
      and serum Cu levels in CMWs.

PMID- 21882070
TI  - Stimulation of fibroblast proliferation by insoluble gadolinium salts.
AB  - The purpose of this study was to assess insoluble salts containing gadolinium
      (Gd(3+)) for effects on human dermal fibroblasts. Responses to insoluble Gd(3+)
      salts were compared to responses seen with Gd(3+) solubilized with organic
      chelators, as in the Gd(3+)-based contrast agents (GBCAs) used for magnetic
      resonance imaging. Insoluble particles of either Gd(3+) phosphate or Gd(3+)
      carbonate rapidly attached to the fibroblast cell surface and stimulated
      proliferation. Growth was observed at Gd(3+) concentrations between 12.5 and 125
      MUM, with toxicity at higher concentrations. Such a narrow window did not
      characterize GBCA stimulation. Proliferation induced by insoluble Gd(3+) salts
      was inhibited in the presence of antagonists of mitogen-activated protein kinase
      and phosphatidylinositol 3-kinase signaling pathways (similar to chelated Gd(3+))
      but was not blocked by an antibody to the platelet-derived growth factor receptor
      (different from chelated Gd(3+)). Finally, high concentrations of the insoluble
      Gd(3+) salts failed to prevent fibroblast lysis under low-Ca(2+) conditions,
      while similar concentrations of chelated Gd(3+) were effective. In conclusion,
      while insoluble Gd(3+) salts are capable of stimulating fibroblast proliferation,
      one should be cautious in assuming that GBCA dechelation must occur in vivo to
      produce the profibrotic changes seen in association with GBCA exposure in the
      subset of renal failure patients that develop nephrogenic systemic fibrosis.

PMID- 21882071
TI  - (+/-)-catechin, a root exudate of the invasive centaurea stoebe lam. (Spotted
      knapweed) exhibits bacteriostatic activity against multiple soil bacterial
      populations.
AB  - Understanding the effects of allelopathic plant chemicals on soil microorganisms
      is critical to understanding their ecological roles and importance in exotic
      plant invasion. Centaurea stoebe Lam. (spotted knapweed), an aggressive invasive
      weed in North America, secretes a racemic mixture of (+/-)-catechin as a root
      exudate. This enantiomeric, polyphenolic compound has been reported to have
      allelopathic effects on surrounding flora and microflora. To better understand
      how catechin affects microbial communities in the root zone of spotted knapweed,
      we assessed its impact on the total culturable bacterial component and numerous
      individual bacterial populations from Romanian (native range) and Montana
      (invaded range) soils. Catechin suppressed total culturable count numbers from
      the bacterial community and inhibited growth of some, but not all, soil bacterial
      populations tested. The native soil bacterial community was significantly more
      resistant to inhibitory effects of catechin than either the invaded or non
      invaded soils. We further show that the inhibitory effect of catechin on nine
      different soil bacterial strains from seven genera was reversible, demonstrating
      that it acts via a bacteriostatic rather than bactericidal mechanism. These
      findings suggest that catechin might affect bacterial community composition and
      activity in the root zone.

PMID- 21882072
TI  - A comparison of the social and sexual networks of crack-using and non-crack using
      African American men who have sex with men.
AB  - The role of crack cocaine in accelerating the HIV epidemic among heterosexual
      populations has been well documented. Little is known about crack use as an HIV
      risk factor among African American men who have sex with men (AA MSM), a group
      disproportionately infected with HIV. We sought to compare the social and sexual
      network characteristics of crack-using and non-crack using AA MSM in Baltimore,
      MD, USA and to examine associations of crack use with sexual risk. Participants
      were recruited using street-based and internet-based outreach, printed
      advertisements, word of mouth. Inclusion criteria were being aged 18 years or
      older, African American or of black race/ethnicity, and have self-reported sex
      with another male in the prior 90 days. Crack use was operationalized as self
      report of crack in the prior 90 days. Logistic regression was used to identify
      variables that were independently associated with crack use. Of 230 enrolled AA
      MSM, 37% (n = 84) reported crack use. The sexual networks of crack-using AA MSM
      were composed of a greater number of HIV-positive sex partners, exchange
      partners, and partners who were both sex and drug partners and fewer networks
      with whom they always use condoms as compared to non-crack using AA MSM. Crack
      use was independently associated with increased odds of bisexual identity and
      networks with a greater number of exchange partners, overlap of drug and sex
      partners, and lesser condom use. Results of this study highlight sexual network
      characteristics of crack-smoking AA MSM that may promote transmission of HIV. HIV
      interventions are needed that are tailored to address the social context of crack
      smoking AA MSM risk behaviors.

PMID- 21882073
TI  - Accelerating microfluidic immunoassays on filter membranes by applying vacuum.
AB  - This paper describes a vacuum-accelerated microfluidic immunoassay (we abbreviate
      it as VAMI) by sandwiching a filter membrane between a two-layer chip. A direct
      assay of IgG demonstrated that VAMI could simultaneously achieve higher
      sensitivity and require less time compared with conventional microfluidic
      immunoassays. We further applied VAMI to carry out a 3-step competitive assay
      (including antigen immobilization, competitive reaction and 2(nd) antibody
      reaction) for detecting the illegal food additive Sudan Red. A total assay time
      of 15 min with a limit of detection (LOD) of 1 ng ml(-1) is achieved.

PMID- 21882075
TI  - Bronchoalveolar lavage total cell count in interstitial lung diseases--does it
      matter?
AB  - Bronchoalveolar lavage (BAL) is a useful technique for differential diagnosis of
      various interstitial lung diseases (ILDs) and is usually realized by analysis of
      the differential cell count. This study was conducted to estimate the value of
      bronchoalveolar lavage fluid (BALF) total cell count (TCC) in the diagnosis of
      ILD. We analyzed 237 BAL samples from patients with ILD: sarcoidosis (SA),
      idiopathic pulmonary fibrosis (IPF), cryptogenic organizing pneumonia (COP),
      hypersensitivity pneumonitis (HP), chronic eosinophilic pneumonia (CEP), and
      smoking-related ILD (sr-ILD). The control group consisted of 30 healthy
      volunteers. The statistical analysis revealed significant differences in the BALF
      TCC between healthy controls and patients with SA, IPF, HP, COP, sr-ILD, and
      eosinophilic disorders (mean values 6.9 vs. 14.5, 22.5, 22.8, 20.7, 64.5, and
      27.3 * 10(6), respectively). Logistic regression revealed a significant relation
      between the TCC and ILD diagnosis. We conclude that the TCC, as well as the value
      of total number of inflammatory cells, should be reported in the description of
      BAL.

PMID- 21882074
TI  - Proteasome inhibition prevents development of experimental dermal fibrosis.
AB  - Scleroderma is a chronic fibrotic disorder. Bortezomib, a proteasome inhibitor,
      is reported to attenuate experimentally induced renal and cardiac fibrosis. This
      study aimed to evaluate the preventive and therapeutic efficacies of bortezomib
      on a bleomycin (BLM)-induced scleroderma model. Dermal fibrosis was induced in
      Balb/c mice by subcutaneous BLM (100 MUg/day) injections. Bortezomib (1.6 mg/kg
      twice/week) was applied intraperitoneally to BLM-injected mice during the first 3
      weeks for preventive interventions and in the second 3 weeks for therapeutic
      interventions. IL-4 and TGF-beta1 serum levels, dermal thicknesses, dermal
      inflammatory cell counts, and alpha-SMA-positive fibroblastic cell counts were
      determined, and type-I collagen, NF-kappaBp65, I-kappaBalpha, and JNK1
      expressions were assessed. BLM applications increased serum IL-4 level, dermal
      inflammatory cell counts, alpha-SMA-positive cell counts, expression of type-I
      collagen, NF-kappaB, and JNK1, and dermal thickness in early stage of fibrosis,
      but serum IL-4 level and dermal inflammatory cell counts showed no increases in
      later stages. As a preventive intervention, bortezomib decreased dermal
      thickness, inflammatory cell infiltrations, fibroblastic activity, and expression
      of type-I collagen, NF-kappaB, and JNK1, but did not decrease fibroblastic
      activity and dermal thickness at later stages of fibrosis. Inflammatory status is
      prominent in the early stage of dermal fibrosis, but declines at later stages. In
      BLM-induced dermal fibrosis, bortezomib has a preventive anti-fibrotic and anti
      inflammatory efficacy, but has no therapeutic anti-fibrotic efficacy in
      preexisting tissue fibrosis. These findings suggest that the effect of proteasome
      inhibition in early stages of dermal fibrosis may be related to its anti
      inflammatory effects.

PMID- 21882076
TI  - Atherosclerosis screening by noninvasive imaging for cardiovascular prevention: a
      systematic review.
AB  - BACKGROUND: Noninvasive imaging of atherosclerosis is being increasingly used in
      clinical practice, with some experts recommending to screen all healthy adults
      for atherosclerosis and some jurisdictions mandating insurance coverage for
      atherosclerosis screening. Data on the impact of such screening have not been
      systematically synthesized. OBJECTIVES: We aimed to assess whether
      atherosclerosis screening improves cardiovascular risk factors (CVRF) and
      clinical outcomes. DESIGN: This study is a systematic review. DATA SOURCES: We
      searched MEDLINE and the Cochrane Clinical Trial Register without language
      restrictions. STUDY ELIGIBILITY CRITERIA: We included studies examining the
      impact of atherosclerosis screening with noninvasive imaging (e.g., carotid
      ultrasound, coronary calcification) on CVRF, cardiovascular events, or mortality
      in adults without cardiovascular disease. RESULTS: We identified four randomized
      controlled trials (RCT, n=709) and eight non-randomized studies comparing
      participants with evidence of atherosclerosis on screening to those without
      (n=2,994). In RCTs, atherosclerosis screening did not improve CVRF, but smoking
      cessation rates increased (18% vs. 6%, p=0.03) in one RCT. Non-randomized studies
      found improvements in several intermediate outcomes, such as increased motivation
      to change lifestyle and increased perception of cardiovascular risk. However,
      such data were conflicting and limited by the lack of a randomized control group.
      No studies examined the impact of screening on cardiovascular events or
      mortality. Heterogeneity in screening methods and studied outcomes did not permit
      pooling of results. CONCLUSION: Available evidence about atherosclerosis
      screening is limited, with mixed results on CVRF control, increased smoking
      cessation in one RCT, and no data on cardiovascular events. Such screening should
      be validated by large clinical trials before widespread use.

PMID- 21882077
TI  - A modified Hai-Murphy model of uterine smooth muscle contraction.
AB  - We extend and analyze the Wang and Politi modified Hai-Murphy model of smooth
      muscle cell contractions to capture uterine muscle cell response to variations in
      intracellular calcium concentrations. This model is used to estimate values of
      unknown parameters in uterine smooth muscle cell cross-bridging. Uterine motility
      is responsible for carrying out important processes throughout all phases of the
      nonpregnant female reproductive cycle, including sperm transport, menstruation,
      and embryo implantation. The modified Hai-Murphy partial differential equation
      model accounts for the displacement of myosin cross-bridge heads relative to
      their binding sites. This model was originally developed for the study of airway
      contractions; we now extended it for use in modeling nonisometric uterine
      contractions. Our extended model incorporates cross-bridge position and
      contractile velocity into the original model, resulting in more accurate modeling
      of the initial stages of contraction and modeling nonisometric contractions.
      Numerical simulations show that the contraction rate in our extended model is
      faster than the original Hai-Murphy model. These simulations provide quantitative
      estimates for the increased level of responsiveness of our extended model to
      intracellular calcium concentrations. The extended model and new parameter
      estimates for the cross-bridging can be coupled with uterine flow models to
      advance our understanding of embryonic motility and intrauterine flow.

PMID- 21882078
TI  - Promoted transfection efficiency of pDNA polyplexes-loaded biodegradable
      microparticles containing acid-labile segments and galactose grafts.
AB  - PURPOSE: Targeting to antigen-presenting cells and efficient intracellular
      delivery of pDNA are essential for development of microsphere formulations of DNA
      vaccine. METHODS: Biodegradable polymers containing acid-labile segments and
      galactose grafts were developed to entrap pDNA polyplexes into microspheres,
      which were proposed to promote transfection efficiency of pDNA. RESULTS: Acid
      labile characteristics were approved by the hemolysis capabilities of red blood
      cells and degradation behaviors of matrix polymers; release of pDNA polyplexes
      from microspheres was significantly accelerated after incubation in acid buffers.
      Presence of galactose moieties enhanced cellular uptake of microspheres and
      increased acid-lability due to hydrophilic grafts on acid-labile segments. There
      was no apparent cytotoxicity of blank microspheres; cytotoxicity of pDNA
      polyplexes was significantly decreased after encapsulation into and sustained
      release from microspheres. High transfection efficiency and a dose-dependent
      transfection were indicated for pDNA polyplex-loaded acid-labile microspheres
      when balancing with cytotoxicity. CONCLUSIONS: Integration of acid-lability,
      targeting effect into full biodegradable backbone represents an exciting approach
      to promote transfection efficiency through modulating release of pDNA polyplexes,
      targeting to antigen-presenting cells and intracellular delivery of pDNA.

PMID- 21882079
TI  - Translational lessons from a case of combined heart and liver transplantation for
      familial hypercholesterolemia 20 years post-operatively.
AB  - We review the lessons from a case of combined heart and liver transplantation
      (CHLT) 20 years post-operatively from the molecular to clinical levels. CHLT
      replaces cardiac function and provides a new source of Low density lipoprotein
      receptors (LDL-R) known to be deficient in Familial Hypercholesterolaemia. Little
      is known of the long-term outcomes of this strategy. We review the lessons from a
      case of CHLT 20 years post-operatively, which illustrate the successful
      transition from the molecular understanding of the pathophysiology to the
      clinical therapy. Most importantly, there is evidence that transplantation of
      multiple organs from a single donor promotes operational tolerance, especially in
      the case of the liver. This lady presented in severe heart failure with advanced
      atherosclerotic disease resulting in coronary artery and aortic valve stenosis.
      The serum LDL-C concentration of 13 mmol/L was refractory to conventional
      therapy. Genetic analysis showed a large deletion on one allele of the LDL-R, and
      a mutant allele that produced a receptor which was delayed in its transport to
      the cell membrane and had 10% of normal receptor activity. The patient had a
      normalised lipid-profile directly after CHLT (2.1 mmol/L), and this has remained
      stable since the time of operation. Apart from a minor episode of cardiac
      rejection at 3 weeks post-CHLT, the patient has had excellent heart and liver
      function throughout. This patient has not experienced any signs of rejection,
      despite only low-dose immunosuppression. We review what we have learnt from this
      case at the molecular and clinical levels.

PMID- 21882080
TI  - Hepatocellular carcinoma complicated by gastroduodenal obstruction: palliative
      treatment with metallic stent placement.
AB  - PURPOSE: To evaluate the clinical effectiveness of self-expandable metallic
      stents in seven patients with malignant gastroduodenal obstruction caused by
      inoperable hepatocellular carcinoma (HCC). METHODS: Seven patients with
      gastroduodenal obstruction caused by advanced HCC underwent metallic stent
      placement from 2003 to 2010. These patients had total dysphagia (n = 5) or were
      able to eat only liquids (n = 2) before stent placement. Patients had Eastern
      Cooperative Oncology Group performance scores of 2 or 3, and Child-Pugh
      classification B or C. RESULTS: Stent placement was technically successful in all
      seven patients (100%) and clinically successful in six (86%). Five patients could
      eat a soft diet, and one patient tolerated regular diet after stent placement.
      Stent-related obstructive jaundice occurred in one patient. One patient had
      hematemesis 11 days after stent placement. Overall mean survival was 51 days
      (range, 10-119 days). Stent patency was preserved in six patients with clinical
      success until death. CONCLUSION: Placement of a covered self-expandable metallic
      stent may offer good palliation in patients with gastroduodenal obstruction due
      to advanced HCC.

PMID- 21882081
TI  - Quality improvement guidelines for percutaneous catheter-directed intra-arterial
      thrombolysis and mechanical thrombectomy for acute lower-limb ischemia.
AB  - Percutaneous catheter-directed intra-arterial thrombolysis is a safe and
      effective method of treating acute and subacute lower limb ischemia, as long as
      accurate patient selection and procedural monitoring are ensured. Although
      larger, controlled trials are needed to establish the role of PTDs in ALI,
      mechanical thrombectomy could currently be applied combined with lytic infusion
      in selected cases where rapid recanalization is required or as a stand-alone
      therapy when the administration of thrombolytic agents is contraindicated.

PMID- 21882083
TI  - Graphical model based multivariate analysis (GAMMA): an open-source, cross
      platform neuroimaging data analysis software package.
AB  - The GAMMA suite is an open-source, cross-platform data-mining software package
      designed to analyze neuroimaging data. Analyzing brain image volumes is a very
      challenging problem, due to undersampling and the potential for multivariate
      nonlinear interactions among variables. The GAMMA suite provides a set of tools
      to facilitate the analysis of neuroimaging data.

PMID- 21882082
TI  - The cardiac magnetic resonance (CMR) approach to assessing myocardial viability.
AB  - Cardiac magnetic resonance (CMR) is a noninvasive imaging method that can
      determine myocardial anatomy, function, perfusion, and viability in a relative
      short examination. In terms of viability assessment, CMR can determine viability
      in a non-contrast enhanced scan using dobutamine stress following protocols
      comparable to those developed for dobutamine echocardiography. CMR can also
      determine viability with late gadolinium enhancement (LGE) methods. The
      gadolinium-based contrast agents used for LGE differentiate viable myocardium
      from scar on the basis of differences in cell membrane integrity for acute
      myocardial infarction. In chronic myocardial infarction, the scarred tissue
      enhances much more than normal myocardium due to increases in extracellular
      volume. LGE is well validated in pre-clinical and clinical studies that now span
      from almost a cellular level in animals to human validations in a large
      international multicenter clinical trial. Beyond infarct size or infarct
      detection, LGE is a strong predictor of mortality and adverse cardiac events. CMR
      can also image microvascular obstruction and intracardiac thrombus. When combined
      with a measure of area at risk like T2-weighted images, CMR can determine infarct
      size, area at risk, and thus estimate myocardial salvage 1-7 days after acute
      myocardial infarction. Thus, CMR is a well validated technique that can assess
      viability by gadolinium-free dobutamine stress testing or late gadolinium
      enhancement.

PMID- 21882084
TI  - New luminescent bioprobes Eu(lll)-phloroglucinol derivatives and their
      spectrofluorimetric, electrochemical interactions with nucleotides and DNA.
AB  - Two new ligands derived from phloroglucinol 2-{[(4-methoxy benzoyl)oxy]} methyl
      benzoic acid[L1] and 2-{[(4-methyl benzoyl)oxy] methyl} benzoic acid[L2] were
      synthesized. The solid complex Eu(III)-L2 has been synthesised and characterized
      by elemental analysis, UV and IR spectra. The reaction of Eu(III) with the two
      synthesized ligands has been investigated in I = 0.1 mol dm(-3) p-toluene
      sulfonate by cyclic voltammetry and square wave voltammetry. The reaction of Eu
      (III)-L1 and Eu (III)-L2 binary complexes with nucleotide 5'-AMP, 5'-ADP, 5'-ATP,
      5'- GMP, 5'-IMP, and 5'-CMP has been investigated using UV, fluorescence and
      electrochemical methods. The experimental conditions were selected such that self
      association of the nucleotides and their complexes was negligibly small, that is,
      the monomeric complexes were studied. The interaction of the Eu(III)-L1 or L2
      solid complexes with calf-thymus DNA has been investigated by fluorescence and
      electrochemical methods including cyclic voltammetery(CV), differential pulse
      polarography (DPP) and square wave voltammetry (SWV) on a glassy carbon
      electrode. The fluorescence intensity of Eu(III)-L2 complex was enhanced with the
      addition of DNA. Under optimal conditions in phosphate buffer pH 7.0 at 25 
      degrees C the linear range is 3-20 MUM for calf thymus DNA (CT-DNA) and the
      corresponding determination limit is 1.8 MUM.

PMID- 21882085
TI  - Treatment duration of febrile urinary tract infections.
AB  - Although febrile urinary tract infections (UTIs) are relatively common in adults,
      data on optimal treatment duration are limited. Randomized controlled trials
      specifically addressing the elderly and patients with comorbidities have not been
      performed. This review highlights current available evidence. Premenopausal, non
      pregnant women without comorbidities can be treated with a 5-7 day regimen of
      fluoroquinolones in countries with low levels of fluoroquinolone resistance, or,
      if proven susceptible, with 14 days of trimethoprim-sulfamethoxazole. Oral beta
      lactams are less effective compared with fluoroquinolones and trimethoprim
      sulfamethoxazole. In men with mild to moderate febrile UTI, a 2-week regimen of
      an oral fluoroquinolone is likely sufficient. Although data are limited, this
      possibly holds even in the elderly patients with comorbidities or bacteremia.

PMID- 21882086
TI  - Gynecologic clostridial toxic shock in women of reproductive age.
AB  - Clostridial toxic shock, caused by Clostridium sordellii or Clostridium
      perfringens, is a rare and largely fatal syndrome among reproductive-aged women
      with genital tract infection, and may occur following various pregnancy outcomes
      or without pregnancy. Clinicians should be aware of common clinical features of
      this very rapidly-progressing syndrome including abdominal pain, tachycardia,
      hypotension, third-space fluid accumulations, hemoconcentration, and marked
      leukemoid response, often with lack of fever. In this review, we summarize known
      cases through mid-2011 and information on clinical presentation, diagnosis,
      treatment, and results of recent investigations regarding pathogenesis, including
      germination, toxins, and host response that may have important implications for
      development of preventive or therapeutic interventions.

PMID- 21882087
TI  - Low-dose contrast protocol using the test bolus technique for 64-detector
      computed tomography coronary angiography.
AB  - PURPOSE: We evaluated low-contrast injection protocols for coronary computed
      tomography angiography (CTA) using a 64-detector scanner and the test bolus
      technique. MATERIALS AND METHODS: We randomly assigned 60 patients undergoing
      coronary CTA to one of two contrast material (CM) injection protocols. For the
      low-contrast dose protocol (P(low)), the patients received injections of iohexol
      350 [0.7 ml/kg body weight (BW)] during 9 s, and the test-bolus technique was
      used. Under the conventional protocol (P(conv)), they received iohexol-350 (1.0
      ml/kg BW) during 15 s, and bolus tracking was used. We compared the protocols for
      attenuation values in the ascending aorta and coronary arteries and for the
      amount of CM required. RESULTS: There was no significant difference in the mean
      CT attenuation of the ascending aorta and coronary arteries between the P(low)
      and P(conv) groups. The amount of CM was significantly less with P(low) than with
      P(conv) [49.7 +/- 6.4 ml (main bolus: 39.7 +/- 6.4 ml) vs. 57.0 +/- 10.1 ml, P <
      0.01]. CONCLUSION: With 64-detector CTA of the heart, the low-dose and short
      injection-duration protocol with the test-injection technique provides vessel
      attenuation comparable to that obtained with the standard-dose protocol with the
      bolus-tracking technique.

PMID- 21882088
TI  - High-resolution magnetic resonance imaging of rotator cuff tears using a
      microscopy coil: noninvasive detection without intraarticular contrast material.
AB  - PURPOSE: The aim of this study was to evaluate the feasibility of high-resolution
      magnetic resonance imaging (MRI) using a microscopy coil for the diagnosis of
      rotator cuff tears by comparing the method to conventional MRI and MRI
      arthrography. MATERIALS AND METHODS: A total of 68 shoulders were prospectively
      studied using a 1.5-T MRI unit. Conventional MRI scans were obtained with a
      surface coil and high-resolution MRI scans with a microscopy coil. MRI
      arthrography was performed in 28 shoulders using a surface coil. MRI evaluation
      of tears of rotator cuff tendons was compared with arthroscopic findings and
      surgical results. RESULTS: The surgery revealed 40 full-thickness tears, 13
      partial-thickness tears, and 15 intact cuffs. In all, 35 (88%) full-thickness
      tears were correctly diagnosed on conventional MRI and 40 (100%) on high
      resolution MRI. MR arthrography delineated 11 of 12 (92%) full-thickness tears.
      Altogether, 5 (38%) of the partial-thickness tears were detected on conventional
      MRI, and 12 (92%) were clearly demonstrated on high-resolution MRI. MRI
      arthrography depicted three (60%) of five partial-thickness tears. High
      resolution MRI showed higher sensitivity than conventional MRI (P < 0.05) and had
      values equivalent to those of MRI arthrography for diagnosing partial-thickness
      tears. CONCLUSION: High-resolution MRI with a microscopy coil is a feasible,
      noninvasive technique for diagnosing rotator cuff tears.

PMID- 21882089
TI  - Imaging features of invasive lobular carcinoma: comparison with invasive ductal
      carcinoma.
AB  - PURPOSE: The aim of this study was to evaluate the imaging findings of invasive
      lobular carcinoma (ILC) compared to those of invasive ductal carcinoma (IDC).
      MATERIALS AND METHODS: The study included ILCs (n = 27) and IDCs (n = 85).
      Imaging findings were retrospectively evaluated, according to the BI-RADS
      lexicon. We compared the imaging findings, multiplicity, and magnetic resonance
      imaging (MRI) detection accuracy of ILC with those of IDC. RESULTS: At
      mammography, normal findings and mass lesions were more frequent with ILCs (14.8%
      and 59.2%, respectively) than with IDCs (1.2% and 44.7%, respectively) (P =
      0.009). With ultrasonography (US), posterior acoustic shadowing was more
      frequently seen in ILCs (59.2%) than in IDCs (15.8%) (P < 0.001). With MRI, both
      ILCs and IDCs most commonly appeared as a heterogeneously enhancing, irregular
      mass with a spiculated border. Multifocality was more frequently associated with
      ILCs (40.7%) than with IDCs (14.1% 1% 0.002). However, multicentricity and
      bilaterality were not different between the two groups. The sensitivity and
      specificity of MRI for the detection of multiplicity were 91.6% and 73.3%,
      respectively, for ILCs and 83.3% and 80.3%, respectively, for IDCs. CONCLUSION:
      Normal findings, mass lesions on mammography, and posterior acoustic shadowing on
      US were more frequently associated with ILCs than with IDCs. Multifocality was
      more prevalent with ILCs than with IDCs.

PMID- 21882090
TI  - Radiology reading-caused fatigue and measurement of eye strain with critical
      flicker fusion frequency.
AB  - PURPOSE: The aim of this study was to investigate eye fatigue that could impair
      diagnostic accuracy by measuring the critical flicker fusion frequency (CFFF)
      before and after reading. MATERIALS AND METHODS: CFFF was measured before and
      after about 4 h of health checkup reading in seven healthy volunteer
      radiologists. A questionnaire was also completed on duration of sleep the night
      before the experiment, average duration of sleep, and subjective fatigue using a
      visual analog scale (corrected to a 0-1 scale, 0 indicating the worst fatigue
      ever experienced). RESULTS: After-reading subjective fatigue was significantly
      greater (before 0.52 +/- 0.15, after 0.42 +/- 0.15), and CFFF was significantly
      lower (before 40.9 +/- 2.4, after 39.9 +/- 2.0). There was no significant
      correlation between subjective fatigue and CFFF, either before or after or
      between before- and after-reading differences in subjective fatigue and CFFF.
      Shorter duration of sleep the night before significantly correlated with lower
      CFFF (Pearson's correlation coefficient): before 0.42, P = 0.0047; after 0.52, P
      = 0.0003. CONCLUSION: CFFF declines after reading and can be considered useful as
      an indicator of fatigue induced by radiology reading. CFFF declines significantly
      when sleep is reduced the day before reading without correlation with subjective
      fatigue, meaning that sleep deprivation can cause an unaware decline in visual
      function.

PMID- 21882091
TI  - Determination of the cutoff level of apparent diffusion coefficient values for
      detection of prostate cancer.
AB  - PURPOSE: The aim of this study was to determine the cutoff level of apparent
      diffusion coefficient (ADC) values for diagnosing prostate cancer. MATERIALS AND
      METHODS: A total of 45 consecutive patients with prostate cancer who underwent
      diffusion-weighted magnetic resonance imaging (MRI) with ADC maps before radical
      prostatectomy were included in this retrospective study. MRI findings were
      correlated retrospectively with histopathological results of surgical specimens.
      Comparisons of ADC values between cancer and noncancer areas were performed with
      the two-tailed unequal variance t-test. The cutoff ADC level was determined in a
      way to achieve the best accuracy for detecting prostate cancer. RESULTS: The mean
      ADC value of all the cancer lesions (n =60) was 1.04 +/- 0.31 (*10(-3) mm(2)/s).
      In the peripheral zone, the mean ADC values of cancer lesions and noncancer areas
      were 1.07 +/- 0.35 and 1.94 +/- 0.31, respectively (P < 0.001). In the transition
      zone, the mean ADC values of cancer lesions and noncancer areas were 1.00 +/-
      0.22 and 1.56 +/- 0.14, respectively (P<0.001). The cutoff level for the ADC
      value was determined to be 1.35*10(-3) mm(2)/s. It provided sensitivity,
      specificity, and accuracy of 88%, 96%, and 93%, respectively. CONCLUSION: The
      cutoff ADC level determined on the basis of the results obtained from radical
      prostatectomy specimens can help differentiate malignant from nonmalignant
      lesions.

PMID- 21882092
TI  - Multidetector-row computed tomography findings of sclerosing mesenteritis with
      associated diseases and its prevalence.
AB  - PURPOSE: Our aim was to report the multidetector-row computed tomography (MDCT)
      findings of sclerosing mesenteritis, which is a rare disease characterized by
      chronic nonspecific inflammation of mesenteric adipose tissue. It has associated
      diseases, and we explored its prevalence. MATERIALS AND METHODS: A total of 2100
      patients were evaluated retrospectively for sclerosing mesenteritis between
      December 2007 and May 2009. Signs and symptoms, associated diseases, laboratory
      data, surgical histories, and related findings of a misty mesentery, which
      corresponds to sclerosing mesenteritis on MDCT, were recorded. RESULTS: Misty
      mesentery findings were seen in 51 (2.43%; 35 men) patients. Their ages ranged
      between 33 and 78 years (mean 56.2 years). The most frequent complaint of
      patients was abdominal pain (n = 19; 37.2%). The most prominent possible
      causative and/or associated factors in our study were malignancy (n = 9; 17.6%),
      previous surgery (n = 17; 33.3%), smoking (n = 20; 39.2%), coronary artery
      disease (n = 9; 17.6%), urolithiasis (n = 10; 19.6%), hypertension (n = 18;
      35.2%), hyperlipidemia (n = 13; 25.5%), and diabetes mellitus (n = 11; 21.5%). On
      MDCT, density values in mesenteric fat (-62.8 +/- 18.6 HU) were significantly
      higher than the values for subcutaneous (-103.9 +/- 5.8 HU) and retroperitoneal (
      105 +/- 6 HU) fatty tissues (both P < 0.0001). A partially hyperdense stripe (n =
      37; 72.6%), well-defined soft tissue nodules (100%), hypodense fatty halo
      enclosing vessels (n = 1; 1.9%), and nodules (n = 12; 23.5%) were demonstrated in
      most of the patients. CONCLUSION: The diagnosis of sclerosing mesenteritis has
      increased with the more frequent use of MDCT and the popularization of the DICOM
      viewer. Defined hallmarks on MDCT can be helpful for differentiating sclerosing
      mesenteritis from other pathologies.

PMID- 21882093
TI  - Investigation of protective effect of hydrogen-rich water against cisplatin
      induced nephrotoxicity in rats using blood oxygenation level-dependent magnetic
      resonance imaging.
AB  - PURPOSE: The aim of this study was to assess the mechanism of the protective
      effect of hydrogen-rich water (HW) against cisplatin (CP)-induced nephrotoxicity
      in rats using blood oxygenation level-dependent (BOLD) magnetic resonance imaging
      (MRI). MATERIALS AND METHODS: Apparent transverse relaxation time-weighted images
      (T2 WI) were acquired in 28 rats. The control group (n = 7) had free access to
      standard water (SW) and no CP injection. The CP group (n = 7) had free access to
      SW and was given a CP injection on day 0. The CP+HW group (n = 7) had free access
      to HW and had a CP injection. The HW group (n = 7) had free access to HW and no
      CP injection. The apparent transverse relaxation rate (R2) was estimated from T2
      WI. RESULTS: In the CP+HW group, the R2 value in the medulla normalized by the
      value of the day 0 was significantly greater than that in the CP group on days 4
      and 7. The creatinine and blood urea nitrogen levels in the CP group were
      significantly higher than those in the control, CP+HW, and HW groups. CONCLUSION:
      BOLD MRI may be useful for demonstrating the change in R2 in CP-induced
      nephrotoxicity in rats. The changes in the CP+HW group were suspected to be due
      to a reduction of cytotoxic oxygen radicals.

PMID- 21882094
TI  - Central nervous system myelomatosis with optic neuropathy and intramedullary
      spinal cord compression responding to radiation therapy.
AB  - Central nervous system (CNS) involvement by multiple myeloma is a rare
      complication that occurs in less than 1% of cases. The purpose of this report is
      to highlight the unique presentation and treatment of a patient with CNS
      myelomatosis. A 58-year-old Caucasian woman with multiple myeloma developed
      subacute vision loss bilaterally and was found to have plasma cells in her
      cerebrospinal fluid. Using a helmet field to 25 Gy in 10 fractions, her vision
      was stabilized with radiotherapy. After developing right upper extremity numbness
      and weakness, magnetic resonance imaging revealed intramedullary spinal cord
      lesions from C5 to C7. She received radiotherapy to 25 Gy in 10 fractions from C4
      to T1, with improvement in upper extremity strength after 15 Gy. Although CNS
      involvement by multiple myeloma is a rare complication, increasing awareness is
      necessary for clinicians to consider meningeal myelomatosis in patients with this
      neoplasm.

PMID- 21882095
TI  - Role of external beam radiotherapy for arteriovenous malformation of the
      pancreas.
AB  - Pancreatic arteriovenous malformation (PAVM) is rare and is mainly reported from
      Asian countries. We incidentally encountered an asymptomatic, early-stage PAVM in
      a patient who presented with portal venous distention, Child B liver cirrhosis,
      and hepatoma. The PAVM had multiple feeding arteries and drainage into the portal
      vein and varices. Because surgery was not indicated, after considering the risks
      and bene-fits the patient chose treatment with 40 Gy of conformal radiotherapy
      for 4 weeks. Computed tomography performed 6 months later revealed reduction in
      the size of the PAVM. Treatment had lasting effects for 18 months without
      significant toxicity. As observed in many reports of radiotherapy for various
      AVMs, the radiotherapy may stall self-augmenting growth of the AVM. Conventional
      fractionated radiotherapy of 40 Gy may be a useful choice for early-stage PAVM.

PMID- 21882096
TI  - Apparition of iodinated contrast agents in twin neonatal gastrointestinal tracts
      after maternal contrast-enhanced computed tomography.
AB  - We describe a case of the appearance of iodinated contrast agents in the same
      locations of twins' neonatal gastrointestinal tracts 1 day after maternal
      contrast-enhanced computed tomography (CT). The CT examination had been performed
      on the expectant mother for suspected deep venous thrombosis on the day previous
      to the twin delivery. At 23 h after the CT examination and after cesarean
      section, iodinated contrast agents appeared in the same place in the twins'
      neonatal gastrointestinal tracts, mainly in the ascending colon, on plain
      abdominal radiographs. Radiologists, obstetricians, and pediatricians should
      understand the mechanism of appearance of iodinated contrast agents in fetal
      gastrointestinal tracts when the expectant mother had been given iodinated
      contrast agents intravenously shortly before delivery.

PMID- 21882097
TI  - Multinodular pseudolymphoma of the liver: computed tomography and magnetic
      resonance imaging findings.
AB  - A 60-year-old woman who had had a history of renal cell carcinoma with
      intraperitoneal recurrence presented with multiple liver masses. Computed
      tomography demonstrated multiple enhancing lesions in the both lobes of the
      liver, and there was an apparent small vessel coursing within one of the lesions.
      On magnetic resonance imaging, masses showed slight T1 and T2 prolongation, and
      restricted diffusion: On the hepatobiliary phase of liver-specific contrast agent
      enhancement, lesions were shown as low signal intensity of varying degree. Liver
      metastases from renal cell carcinoma were suspected, and partial hepatectomy was
      performed for the superficially located nodules to make a definitive diagnosis.
      The final pathological diagnosis was reactive lymphoid hyperplasia or
      pseudolymphoma of the liver.

PMID- 21882098
TI  - Unusual presentation of an anterior sacral meningocele: magnetic resonance
      imaging, multidetector computed tomography, and fistulography findings of
      bacterial meningitis secondary to a rectothecal fistula.
AB  - An anterior sacral meningocele, a rare congenital anomaly, manifested in a
      previously healthy 44-year-old woman with findings of meningitis, including
      headache, vomiting, unconsciousness, and fever. Nontraumatic pneumocephalus,
      tetraventricular hydrocephalus, fluid-fluid level at the lateral ventricles, and
      pial enhancement were observed on multidetector computed tomography. A
      ventricular drainage catheter was placed to decompress the hydrocephalus, and
      drainage was performed urgently. Escherichia coli was isolated from the drainage
      material. Whole-spine magnetic resonance imaging and fistulography were
      undertaken on the third day after admission to evaluate for anal and urinary
      incontinence and pareses of both upper and lower extremities. Spinal
      arachnoiditis, tethered cord, dysgenesis of the sacrum, and a rectothecal fistula
      were demonstrated. Specific antibiotic treatment and surgery for fistula tract
      excision were performed.

PMID- 21882100
TI  - [Specific immunotherapy].

PMID- 21882101
TI  - [Diaper dermatitis].
AB  - Diaper dermatitis is one of the most common skin diseases during infancy and
      childhood. It is a type of irritant contact eczema resulting from a complex
      interaction between urine and feces under occlusive conditions in combination
      with the hyperhydration of the stratum corneum, pressure and friction under the
      diaper. These conditions pave the way for Candida albicans infection, which is
      often associated with diaper dermatitis. The anogenital region can be involved by
      a variety of dermatoses, so a precise skin examination, detailed history and
      sometimes histologic examination are needed for a precise diagnosis.
      Therapeutically, frequent diaper changes and adequate skin care are most
      important.

PMID- 21882105
TI  - Developmental pharmacokinetics.
AB  - The advances in developmental pharmacokinetics during the past decade reside with
      an enhanced understanding of the influence of growth and development on drug
      absorption, distribution, metabolism, and excretion (ADME). However, significant
      information gaps remain with respect to our ability to characterize the impact of
      ontogeny on the activity of important drug metabolizing enzymes, transporters,
      and other targets. The ultimate goal of rational drug therapy in neonates,
      infants, children, and adolescents resides with the ability to individualize it
      based on known developmental differences in drug disposition and action. The
      clinical challenge in achieving this is accounting for the variability in all of
      the contravening factors that influence pharmacokinetics and pharmacodynamics
      (e.g., genetic variants of ADME genes, different disease phenotypes, disease
      progression, and concomitant treatment). Application of novel technologies in the
      fields of pharmacometrics (e.g., in silico simulation of exposure-response
      relationships; disease progression modeling), pharmacogenomics and biomarker
      development (e.g., creation of pharmacodynamic surrogate endpoints suitable for
      pediatric use) are increasingly making integrated approaches for developmentally
      appropriate dose regimen selection possible.

PMID- 21882104
TI  - Basics and dynamics of neonatal and pediatric pharmacology.
AB  - Understanding the role of ontogeny in the disposition and actions of medicines is
      the most fundamental prerequisite for safe and effective pharmacotherapeutics in
      the pediatric population. The maturational process represents a continuum of
      growth, differentiation, and development, which extends from the very small
      preterm newborn infant through childhood, adolescence, and to young adulthood.
      Developmental changes in physiology and, consequently, in pharmacology influence
      the efficacy, toxicity, and dosing regimen of medicines. Relevant periods of
      development are characterized by changes in body composition and proportion,
      developmental changes of physiology with pathophysiology, exposure to unique
      safety hazards, changes in drug disposition by major organs of metabolism and
      elimination, ontogeny of drug targets (e.g., enzymes, transporters, receptors,
      and channels), and environmental influences. These developmental components that
      result in critical windows of development of immature organ systems that may lead
      to permanent effects later in life interact in a complex, nonlinear fashion. The
      ontogeny of these physiologic processes provides the key to understanding the
      added dimension of development that defines the essential differences between
      children and adults. A basic understanding of the developmental dynamics in
      pediatric pharmacology is also essential to delineating the future directions and
      priority areas of pediatric drug research and development.

PMID- 21882106
TI  - Principles of therapeutic drug monitoring.
AB  - Therapeutic drug monitoring (TDM) is central to optimize drug efficacy in
      children, because the pharmacokinetics and pharmacodynamics of most drugs differ
      greatly between children and adults. Many factors should be analyzed to implement
      TDM in the pediatric population, including a validated pharmacological parameter
      and an analytical method adapted to children as limited sampling volumes and high
      sensitivity are required. The use of population approaches, new analytical
      methods such as saliva and dried blood spots, and pharmacodynamic monitoring give
      attractive options to improve TDM, individualize therapy in order to optimize
      efficacy and reduce adverse drug reactions.

PMID- 21882107
TI  - Drug delivery and formulations.
AB  - Paediatric drug delivery is a major challenge in drug development. Because of the
      heterogeneous nature of the patient group, ranging from newborns to adolescents,
      there is a need to use appropriate excipients, drug dosage forms and delivery
      devices for different age groups. So far, there is a lack of suitable and safe
      drug formulations for children, especially for the very young and seriously ill
      patients. The new EU legislation will enforce paediatric clinical trials and drug
      development. Current advances in paediatric drug delivery include interesting new
      concepts such as fast-dissolving drug formulations, including orodispersible
      tablets and oral thin strips (buccal wafers), and multiparticulate dosage forms
      based on mini-tabletting or pelletization technologies. Parenteral administration
      is likely to remain the first choice for children in the neonatal period and for
      emergency cases. Alternative routes of administration include transdermal,
      pulmonary and nasal drug delivery systems. A few products are already available
      on the market, but others still need further investigations and clinical proof of
      concept.

PMID- 21882108
TI  - Development of paediatric medicines: concepts and principles.
AB  - The term "off-label use of drugs in children" is common to current medical
      practice. A look into the historical context helps to elucidate the framework for
      the use of medicines in children. Proper drug labels are relatively new in
      history. They emerged half a century ago when U.S. legislation forced
      manufacturers to prove the safety and efficacy of drugs by adequate clinical
      trials. Today pharmaceutical progress is so obvious and well established that the
      discrepancy between its benefit for adults as compared to children started to be
      perceived by champions in different institutions. There is an increased
      understanding of the child's physiology during developmental growth, of the
      maturation of enzyme systems, of the pharmacokinetics and pharmacodynamics and of
      the differences in disease processes. The involved institutions include
      legislators, government, regulatory authorities, academic scientists,
      pharmaceutical companies, the WHO, to name just the most prominent ones, but
      there are many more. Driving forces for the improvement of medicines for children
      include societal priorities, the involvement of science, the mission of
      regulatory authorities the role of clinical pharmacologists, paediatricians, and
      the characteristics of our market-driven economy with its chaotic, contradictory
      and lively elements. We do not live in an ideal world, but there is progress, and
      children are likely to benefit from it.

PMID- 21882109
TI  - Study design and simulation approach.
AB  - Modeling and simulation techniques are a mainstay of clinical drug development
      and are particularly useful to support clinical trials in children. If a
      pediatrician wants to use these tools most efficiently, a basic understanding of
      the principles and methods of classical and novel techniques of modeling and
      simulation is essential. Key elements comprise the definition and description of
      terms like deterministic simulation, Monte Carlo simulation, classical "top down"
      or novel "bottom up" approach, as well as the term "virtual world simulation."
      The illustrated examples in this chapter from pediatric clinical trials will help
      to understand and demonstrate these key elements. The importance of the
      understanding of developmental physiology and pharmacokinetics will become
      visible when explaining novel "bottom up" approaches like physiologically based
      pharmacokinetic simulations which also bridge to current research tools from
      other areas such as systems biology using mathematical models to describe
      biological systems.

PMID- 21882110
TI  - Efficacy assessment in paediatric studies.
AB  - Even though the regulatory authorities to some extent accept the extrapolation of
      efficacy data from adults to paediatric patients, it is often the case that
      differences in the disease process and the developmental stage of the children
      prevent the extrapolation of efficacy in these populations. Where efficacy
      studies are needed, the development, validation, and employment of different
      endpoints for specific age and developmental subgroups become necessary. Children
      are in continuous development and any measure to assess the efficacy of an
      intervention should take carefully into account how this development affects the
      endpoints, including the performance capacity of the child and differences in the
      condition and symptoms presented. Clinical endpoints that are used in the adult
      trials to evaluate treatment effect may not be suitable in paediatric studies.
      The development of surrogate endpoints for benefit and risk assessment in
      children is necessary. Collaboration between the academic researchers,
      pharmaceutical industry, and regulatory authorities is needed to meet the
      challenges in proper validation of biomarkers and surrogate endpoints in
      paediatric trials.

PMID- 21882112
TI  - Small sample approach, and statistical and epidemiological aspects.
AB  - In this chapter, the design of pharmacokinetic studies and phase III trials in
      children is discussed. Classical approaches and relatively novel approaches,
      which may be more useful in the context of drug research in children, are
      discussed. The burden of repeated blood sampling in pediatric pharmacokinetic
      studies may be overcome by the population pharmacokinetics approach using
      nonlinear mixed effect modeling as the statistical solution to sparse data.
      Indications and contraindications for phase III trials are discussed: only when
      there is true "equipoise" in the medical scientific community, it is ethical to
      conduct a randomized clinical trial. The many reasons why a pediatric trial may
      fail are illustrated with examples. Inadequate sample sizes lead to inconclusive
      results. Twelve classical strategies to minimize sample sizes are discussed
      followed by an introduction to group sequential design, boundaries design, and
      adaptive design. The evidence that these designs reduce sample sized between 35
      and 70% is reviewed. The advantages and disadvantages of the different approaches
      are highlighted to give the reader a broad idea of the design types that can be
      considered. Finally, working with DMCs during the conduct of trials is
      introduced. The evidence regarding DMC activities, interim analysis results, and
      early termination of pediatric trials is presented. So far reporting is
      incomplete and heterogeneous, and users of trial reports may be misled by the
      results. A proposal for a checklist for the reporting of DMC issues, interim
      analyses, and early stopping is presented.

PMID- 21882111
TI  - Safety assessment in pediatric studies.
AB  - It typically takes many years before an association of a drug with a rare,
      serious adverse reaction is established. As related to pediatric drug use,
      evidence is even more erratic, as most drugs are used off labels. To enhance
      child safety, there is an urgent need to develop robust and rapid methods to
      identify such associations in as timely a manner as possible. In this chapter,
      several novel methods, both clinically based pharmacoepidemiological approaches
      and laboratory-based methods, are described.

PMID- 21882113
TI  - Sample collection, biobanking, and analysis.
AB  - Pediatric pharmacokinetic studies require sampling of biofluids from neonates and
      children. Limitations on sampling frequency and sample volume complicate the
      design of these studies. In addition, strict guidelines, designed to guarantee
      patient safety, are in place. This chapter describes the practical implications
      of sample collection and their storage, with special focus on the selection of
      the appropriate type of biofluid and withdrawal technique. In addition, we
      describe appropriate measures for storage of these specimens, for example, in the
      context of biobanking, and the requirements on drug assay methods that they pose.
      Pharmacokinetic studies in children are possible, but they require careful
      selection of an appropriate sampling method, specimen volume, and assay method.
      The checklist provided could help prospective researchers with the design of an
      appropriate study protocol and infrastructure.

PMID- 21882114
TI  - Ethical considerations in conducting pediatric research.
AB  - The critical need for pediatric research on drugs and biological products
      underscores the responsibility to ensure that children are enrolled in clinical
      research that is both scientifically necessary and ethically sound. In this
      chapter, we review key ethical considerations concerning the participation of
      children in clinical research. We propose a basic ethical framework to guide
      pediatric research, and suggest how this framework might be operationalized in
      linking science and ethics. Topics examined include: the status of children as a
      vulnerable population; the appropriate balance of risk and potential benefit in
      research; ethical considerations underlying study design, including clinical
      equipoise, placebo controls, and non-inferiority designs; the use of data
      monitoring committees; compensation; and parental permission and child assent to
      participate in research. We incorporate selected national (USA) and international
      guidelines, as well as regulatory approaches to pediatric studies that have been
      adopted in the USA, Canada, and Europe.

PMID- 21882115
TI  - Pediatric regulatory initiatives.
AB  - A series of government actions have evolved since the 1990s to facilitate the
      development of medicinal products for pediatric use using a combination of
      incentives and mandates. The initiatives have been successful in stimulating
      activity and interest in products developed for pediatric use. The initiatives
      continue to evolve as experience accumulates and regulatory agencies develop
      robust cooperative programs. A multidimensional program is necessary to achieve
      the necessary goal of aligning pediatric therapeutics with adult therapeutics and
      providing children the most favorable opportunity to benefit and minimize risk to
      vulnerable populations.

PMID- 21882117
TI  - Fetal risks of maternal pharmacotherapy: identifying signals.
AB  - Pregnant women may be exposed to a variety of medications that may exert toxic or
      teratogenic effects on the fetus. Since the thalidomide disaster, physicians and
      pregnant women tend to withhold medications during pregnancy, although the risk
      of teratogenic effect from most drugs in therapeutic doses is nonexistent. This
      chapter will review the principles of teratology and the pharmacoepidemiological
      evidence for drug safety/risk in human gestation.

PMID- 21882116
TI  - Fetal medicine and treatment.
AB  - Fetal medicine covers a broad spectrum of conditions that can be diagnosed before
      birth. Different disorders will require different treatment strategies and there
      is often an important ontogenetic aspect on how and when treatment can be
      implemented. Due to the limited availability there is a general lack of knowledge
      on how pharmacotherapy can be provided in the most efficient way. Until recently
      most knowledge about how different drugs are transferred and metabolized in the
      human fetus is based on very limited observational studies on concentrations of
      drugs in fetal blood and other fetal compartments. It might be that the rapid
      development of other non-invasive methods for fetal diagnostics such as isolation
      of fetal DNA and RNA in maternal serum, NMR imaging and other techniques could in
      the future be explored in fetal pharmacotherapy. Introduction of new treatment
      strategies are often based on extrapolation from experience in neonates and
      adults. However some fetal conditions are very specific for this time period in
      life. This especially entails disturbances in development as malformations, early
      growth restriction and several congenital disorders. Here it might be required to
      introduce new treatment strategies without any previous experience in humans.
      Example of this ethical dilemma is gene therapy for lung growth in severe cases
      of diaphragmatic hernia and early growth restriction. The risk-benefit issues
      need to be discussed in all these alternatives. However, it is likely that the
      concept of the human fetus as a potential patient is still in its infancy and
      with an improved understanding about fetal patho-physiology there will be a
      continued need for better knowledge of pharmacotherapy during this crucial time
      period in life.

PMID- 21882118
TI  - Antiepileptic treatment in pregnant women: morphological and behavioural effects.
AB  - It is well established that children exposed to antiepileptic drugs (AEDs) in
      utero have an increased risk of adverse pregnancy outcomes including foetal
      growth retardation, major congenital malformations and impaired postnatal
      cognitive development. However, due to the significant maternal and foetal risks
      associated with uncontrolled epileptic seizures, AED treatment is generally
      maintained during pregnancy in the majority of women with active epilepsy. The
      prevalence of major malformations in children exposed to AEDs has ranged from 4
      to 10%, 2-4 times higher than in the general population. More recent studies
      suggest a smaller increase in malformation rates. Malformation rates have
      consistently been higher in association with exposure to valproate than with
      carbamazepine and lamotrigine. Some prospective cohort studies also indicate
      reduced cognitive outcome in children exposed to valproate compared to
      carbamazepine and possibly lamotrigine. Information on pregnancy outcomes with
      newer generation AEDs other than lamotrigine are still insufficient.

PMID- 21882119
TI  - Preventive medicines: vaccination, prophylaxis of infectious diseases,
      disinfectants.
AB  - Immunizations belong to the most successful interventions in medicine. Like other
      drugs, vaccines undergo long periods of pre-clinical development, followed by
      careful clinical testing through study Phases I, II, and III before they receive
      licensure. A successful candidate vaccine will move on to be an investigational
      vaccine to undergo three phases of pre-licensure clinical trials in a stepwise
      fashion before it can be considered for approval, followed by an optional fourth
      phase of post-marketing assessment. The overall risk-benefit assessment of a
      candidate vaccine is very critical in making the licensure decision for
      regulatory authorities, supported by their scientific committees. It includes
      analyses of immunogenicity, efficacy, reactogenicity or tolerability, and safety
      of the vaccine. Public trust in vaccines is a key to the success of immunization
      programs worldwide. Maintaining this trust requires knowledge of the benefits and
      scientific understanding of real or perceived risks of immunizations. Under
      certain circumstances, pre- or post-exposure passive immunization can be achieved
      by administration of immunoglobulines. In terms of prevention of infectious
      diseases, disinfection can be applied to reduce the risk of transmission of
      pathogens from patient to patient, health-care workers to patients, patients to
      health-care workers, and objects or medical devices to patients.

PMID- 21882120
TI  - Postmarketing surveillance.
AB  - Postmarketing drug surveillance refers to the monitoring of drugs once they reach
      the market after clinical trials. It evaluates drugs taken by individuals under a
      wide range of circumstances over an extended period of time. Such surveillance is
      much more likely to detect previously unrecognized positive or negative effects
      that may be associated with a drug. The majority of postmarketing surveillance
      concern adverse drug reactions (ADRs) monitoring and evaluation. Other important
      postmarketing surveillance components include unapproved or off-label drug use,
      problems with orphan drugs, and lack of paediatric formulations, as well as
      issues concerning international clinical trials in paediatric population. The
      process of evaluating and improving the safety of medicines used in paediatric
      practice is referred to as paediatric pharmacovigilance. It requires special
      attention. Childhood diseases and disorders may be qualitatively and
      quantitatively different from their adult equivalents. This may affect either
      benefit or risk of therapies (or both), with a resulting impact on the
      risk/benefit balance. In addition, chronic conditions may require chronic
      treatment and susceptibility to ADRs may change throughout the patient's lifetime
      according to age and stage of growth and development. Therefore, paediatric
      pharmacovigillance aspects need to be tailored to a number of variables based on
      heterogeneity of paediatric population. This chapter will summarize and discuss
      the key issues.

PMID- 21882121
TI  - Global aspects of drug development.
AB  - About nine million children die every year before they reach the age of 5 years,
      of conditions largely amendable with existing medicines. Lack of medicines is not
      the single most important health problem of children, but work to provide
      children with better access to appropriate medicines is essential for achievement
      of the child health goals set. Taking into consideration the global aspect in the
      development of paediatric medicines the benefits of the regional paediatric
      initiatives can be spread worldwide. This chapter provides insights in the
      challenges and opportunities of developing paediatric medicines for health needs
      of children in the developing world. The Essential Medicines List for children
      first made available in 2008 serves as an example of the many tools available
      from WHO to improve children's access to the medicines they need.

PMID- 21882122
TI  - Calcium supplementation, osteoporosis and cardiovascular disease.
AB  - Adequate intakes of calcium and vitamin D are essential preventive strategies and
      essential parts of any therapeutic regimen for osteoporosis. However, calcium
      supplementation is not without controversy and benefits on skeletal health need
      to be balanced against potential risks on cardiovascular disease. The published
      data so far suggest a potential detrimental effect of calcium supplement on
      cardiovascular health (i.e. myocardial infarction) although further prospective
      studies are needed to clarify the gradient of risk. Since food sources of calcium
      produce similar benefits on bone density as supplements and dietary calcium
      intake does not seem to be related with adverse cardiovascular effects, calcium
      intake from nutritional sources needs to be enforced. In patients with low
      calcium intake supplements are warranted aiming for a total calcium intake of 800
      to 1000 mg/d together with adequate vitamin D replacement. Nevertheless we should
      keep in mind that for significant reduction in fracture risk, pharmacological
      treatment is mandatory in patients at risk of fractures irrespective of calcium
      and vitamin D supplementation.

PMID- 21882123
TI  - Drug-eluting coronary stents in clinical practice: lessons from the "BAsel Stent
      Kosten-Effektivitats Trials" (BASKET). A review of the BASKET trials.
AB  - In this review of the BAsel Stent Kosten-Effektivitats Trial (BASKET) the trials
      and their impact on coronary stenting practice were examined, basing the clinical
      questions of each study on the findings of the previous study. Are the new drug
      eluting stents (DES) cost-effective compared to standard bare-metal stents (BMS)
      if used in all patients? No. Are there specific subgroups of patients with a
      particular benefit? Yes. A "targeted stent use" was proposed for daily practice.
      What is the long-term safety of DES? Unexpected safety problems were observed.
      Was this a chance finding? No. However, with improved stenting techniques, newer
      stents and intensified antiplatelet regimens late problems were minimised as
      shown in the BASKET-PROspective Validation Examination (BASKET-PROVE). Further
      stent developments? Wait and see! - Many additional questions were raised and
      answered or are still under investigation. Obviously, answers were not always
      simple and needed a closer look and this is discussed. The BASKET trials
      proceeded not only from one question to the other, but also in size and
      methodology. From the restricted single-centre "local" BASKET study to
      multicentre international long-term trials, all prospective, randomized and
      investigator-driven. Their relevance was acknowledged by publications in major
      medical journals as well as by their impact on US and European practice
      guidelines and on DES research. These aspects are summarised in the present
      review, highlighting lessons learned from each study and commenting on the
      possibilities and difficulties of performing such clinical research in
      Switzerland.

PMID- 21882124
TI  - Good for patients, good for doctors.
AB  - The medical liability reforms the Texas Medical Association pushed through eight
      years ago are still paying off. Texas has more physicians, thereby increasing
      patients' access to care; liability insurance premiums have been drastically cut;
      and there are fewer lawsuits. But TMA leaders say physicians must remain vigilant
      and protect the noneconomic damage cap and other provisions won through tort
      reform.

PMID- 21882125
TI  - ZPICs.
AB  - The Zone Program Integrity Contractors (ZPICs) program is a government effort to
      eliminate fraud, waste, and abuse in Medicare. ZPICs perform a range of medical
      review, data analysis, and Medicare audits. While the audits share many
      similarities with other Medicare audits, they do differ in one key aspect:
      potential Medicare fraud implications.

PMID- 21882126
TI  - The Texas twist.
AB  - The accountable care organization is becoming the trendy new health care delivery
      model of the decade. Texas physicians may have an alternative, thanks to
      legislation passed in the special session of the legislature that ended in late
      June. Senate Bill 7 authorized physicians, hospitals, and other health care
      providers to create health care collaboratives, similar to ACOs, to allow
      traditional competitors to join forces to improve quality of care and lower
      overall costs.

PMID- 21882127
TI  - Playing it safe.
AB  - Passed by the Texas Legislature, House Bill 2038, also known as Natasha's Law,
      deals with the prevention, treatment, and oversight of concussions affecting
      student athletes. Among other provisions, the new law requires school districts
      to create concussion oversight teams that must include at least one physician and
      to establish return-to-play protocols that involve evaluation of the athlete by a
      physician.

PMID- 21882128
TI  - [Interventional radiology: state of the art].

PMID- 21882129
TI  - [Reading and interpreting meta-analyses of diagnostic accuracy studies].

PMID- 21882130
TI  - [Visceral medicine 2011 - Interdisciplinarily on the road to continuous
      progress].

PMID- 21882132
TI  - [86-year-old patient with vomiting and loss of consciousness: the Mackler Triad].

PMID- 21882131
TI  - [Clinical symptoms, treatment and outcome of EHEC and EHEC-HUS patients treated
      as in-patients].
AB  - BACKGROUND AND OBJECTIVE: From May to June 2011 an outbreak of Shiga-toxin
      producing Escherichia coli (EHEC) infections occurred in northern Germany leading
      to a great number of patients with hemolytic-uremic syndrome (HUS). A monocentric
      case series from Hamburg is described. MATERIAL AND METHODS: All patients at that
      time presenting with acute diarrhoea at the Asklepios Clinic Barmbek in Hamburg
      were proved for EHEC infections. Clinical data of EHEC and EHEC-HUS patients
      treated as in-patients as well as stool analysis and laboratory results were
      documented. RESULTS: In total, 117 patients suspicious to have EHEC infection
      were treated as in-patients. In 68 patients an EHEC infection (n = 36) or HUS (n
      = 32) could be confirmed. Additional infections with other diarrhoea-causative
      organism could be revealed in 23 of these 68 patients (34 %). The median age of
      the HUS patients was 44 years being significantly lower compared to the age of
      EHEC patients without HUS (51 years, p = 0,04). In the group of HUS patients
      there were significantly more women (26/32 vs. 21/36, p = 0.03). 19 patients with
      HUS dialysis was necessary. In total, a number of 248 plasma separations were
      required. 18 patients developed severe neuro-psychiatric symptoms. One patient
      died. CONCLUSION: This monocentric case series describes one of the so far
      largest published series of mostly young and female patients with EHEC and EHEC
      HUS.

PMID- 21882133
TI  - [Acute abdomen in a patient with ANCA-associated vasculitis].
AB  - HISTORY AND FINDINGS: A 49-year-old man complained of increasing pain in the
      lower left abdomen. Three weeks previously joint pain had developed, and in the
      last 7 days the patient had noted a cutaneous rash at the lower legs. Within
      three days after admission a paralytic ileus developed, progressed and culminated
      in a small bowel perforation. In the 60 cm ileum specimen as well as in the skin
      lesions there was marked intra- und perivascular infiltration with neutrophil
      granulocytes and focal necrosis, but no granuloma. DIAGNOSIS, TREATMENT AND
      COURSE: As the proteinase 3 subtype of antineutrophil cytoplasmic antibodies
      (ANCA) was positive ANCA-associated vasculitis with gastrointestinal, cutaneous
      and kidney involvement was diagnosed. After initiation of cytostatic treatment
      with methylprednisolone boli und cyclophosphamide the patient's condition
      improved. The post-operative course was uneventful. CONCLUSION: ANCA-associated
      vasculitis rarely presents with severe gastrointestinal complications. The
      disease represents an interdisciplinary challenge because of its variable
      clinical presentation and the possibly lethal outcome if not adequately treated.

PMID- 21882134
TI  - [Biologicals first-line in chronic inflammatory bowel disease? Yes].

PMID- 21882135
TI  - [Biologicals first-line in chronic inflammatory bowel disease? No].

PMID- 21882137
TI  - [Diagnostic and therapeutic management of Barrett's esophagus].

PMID- 21882136
TI  - [Helicobacter pylori: an infection with local complications and systemic
      effects].

PMID- 21882138
TI  - [Gastrointestinal neuroendocrine neoplasias: novel individualized therapeutic
      strategies].

PMID- 21882139
TI  - [Management of pancreatic cancer: recent advances].
AB  - Pancreatic cancer is still associated with a poor prognosis and remains the
      fourth leading cause of cancer related mortality. Overall, long-term survival is
      about 5 %. However, when pancreatic cancer can be resected, five-year survival
      rates increase to approximately 25 %. Pancreatic surgery is technically
      challenging and has significantly changed over the past decades with regard to
      technical aspects as well as perioperative care. Standardized resections can be
      carried out with low morbidity and a mortality below 5 % in high volume
      institutions. Furthermore, there is growing evidence that also more extended
      resections including multivisceral approaches, vessel reconstructions or surgery
      for tumor recurrence can be carried out safely with favorable outcomes. In
      addition, about 20 percent of all primarily locally irresectable tumors may
      profit from neoadjuvant radiochemotherapy. The impact of adjuvant chemotherapy
      has increased over recent years, leading to improved long-term survival. Thus,
      pancreatic cancer should be treated in an interdisciplinary team at a pancreatic
      cancer center. Cystic pancreatic tumors (e. g. IPMNs) are diagnosed more and more
      frequently over the past decade. Often, these tumors are diagnosed in
      premalignant or early invasive stages. While the outcome of late tumor stages of
      cystic and ductal pancreatic carcinomas is identical to ductal adenocarcinomas,
      the long-term outcome of prophylactic resection of premalignant or resection of
      early tumor stages of cystic tumors is excellent. Thus, early surgical treatment
      must be considered in cystic pancreatic tumors.

PMID- 21882140
TI  - [Peritoneal carcinomatosis of colorectal cancer: cytoreductive surgery and
      hyperthermic intraperitoneal chemotherapy].
AB  - Peritoneal carcinomatosis caused by colorectal carcinoma is still considered as
      the end-stage of disease. A multi-modal therapeutic concept including maximal
      cytoreduction followed by intraperitoneal hyperthermic chemotherapy (HIPEC) has
      the potential to cure selected patients. In case of peritoneal carcinomatosis
      palliative systemic treatment is no longer the state of the art. This article
      addresses aspects of the disease, the rationale behind peritonectomy with HIPEC,
      and the surgical management of peritoneal carcinomatosis.

PMID- 21882141
TI  - SCN1B is not related to benign partial epilepsy in infancy or convulsions with
      gastroenteritis.
AB  - We hypothesized that benign partial epilepsy in infancy (BPEI) and convulsions
      with gastroenteritis (CwG) may have a similar genetic background, because
      previous studies indicate that clinical features overlap between BPEI and CwG. As
      carbamazepine is effective for cessation of clustering seizures in children with
      BPEI and CwG, some genetic mutations regarding sodium channels may be related to
      the development of BPEI and/or CwG. We focused on SCN1B encoding the voltage
      dependent sodium channel beta subunit. We explored SCN1B mutation in 6 children
      with BPEI and 6 children with CwG. Genomic DNAs were extracted from peripheral
      blood samples accumulated from the patients and all 5 exons of SCN1B were
      amplified by standard PCR amplification. There were no SCN1B mutations or
      pathological single nucleotide polymorphisms in any of the patients, although the
      phenotypes of our patients were typical for BPEI or CwG. Our study demonstrated
      that SCN1B may not be related to the occurrence of BPEI or CwG.

PMID- 21882142
TI  - Spinal subdural effusion - an additional sonographic sign of child abuse.
AB  - PURPOSE: To assess the suitability of spinal ultrasound for the detection of
      spinal subdural hematoma in infants with sustained non-accidental trauma.
      MATERIALS AND METHODS: Six infants (mean age +/- SD 3.3 +/- 1.5 months) admitted
      to our hospital because of suspected non-accidental trauma were examined
      radiologically with ultrasound, CT and/or MRI and skeletal radiography. Twelve
      healthy infants (mean age +/- SD 2.5 +/- 1.4 months) in whom an ultrasound of the
      spine was performed to exclude spinal dysraphism served as controls. RESULTS: All
      six patients with non-accidental trauma (NAT) presented with cranial subdural
      hematoma visualized by ultrasound and CT scan or MRI. Spinal ultrasound detected
      echogenic effusions with floating particles that displaced the undulating
      arachnoidea from the dura mater spinalis in all six patients with NAT. The size
      of the spinal subdural hematoma varied and extended from the cervical spine to
      the cauda equina. The anatomic landmarks (dura mater spinalis, arachnoidea
      spinalis) were identified and confirmed the subdural location. All spinal
      subdural hematomas were asymptomatic and detected by diagnostic ultrasound. None
      of the infants had a pre-existing neurological or hemorrhagic disorder. The plain
      X-rays of the spine in these infants showed no osseous lesion. Spinal subdural
      hematoma was not observed in any of the controls. CONCLUSION: The presence of
      spinal subdural hematoma is a valuable sign of sustained non-accidental trauma in
      infants that can be quickly and easily detected using spinal ultrasound without
      the need for sedation or general anesthesia. Thus, spinal ultrasound should be
      part of the imaging examinations performed in infants with suspected abuse.

PMID- 21882143
TI  - Severe skin burn at needle entry point complicating radiofrequency ablation for
      hepatocellular carcinoma.

PMID- 21882144
TI  - [Assessment of musculoskeletal pain].
AB  - The rationale for a successful treatment of musculoskeletal pain is an adequate
      initial assessment. Standardized questionnaires, modern imaging modalities such
      as computed tomography, magnetic resonance imaging and musculoskeletal ultrasound
      or electrophysiology have enriched our armamentarium in the last decades. Pain
      inducing pathologies can often be identified and treated in a targeted way due to
      these procedures. But none of these techniques allows an adequate judgment of the
      acquired findings. Supplementary tests have to be indicated and interpreted in
      the context of the patient's entire history and the clinical findings. These two
      remain to be the cornerstones of the assessment of painful musculoskeletal
      disorders.

PMID- 21882145
TI  - [Diagnosis of neuropathic pain].
AB  - Neuropathic pain arises from damage, or pathological change, in the peripheral or
      central nervous system. As such, the term neuropathic pain represents a varying
      set of symptoms rather than a single diagnosis. There is no diagnostic gold
      standard for neuropathic pain and so making a diagnosis is based on clinical
      judgement. The essential elements of this process are to identify painful
      symptoms and a clinical history that all match a neuro-anatomical or dermatomal
      pattern. Abnormal responses to nerve damage account for many of the clinical
      features of neuropathic pain. Painful symptoms arising in an area of altered
      sensation (numbness or hyper-excitability) is the hallmark of neuropathic pain.
      Cardinal features are spontaneous pains (pain arising without stimulus) and
      abnormal responses to non-painful (allodynia) or painful stimuli. The diagnostic
      work-up includes screening tools such as pain questionnaires and pain drawings as
      well as information on the history of the disease and a detailed clinical
      neurological examination. Bedside examination is straightforward. The aim is to
      identify altered sensation in the painful area and so responses should be
      compared with a non-painful adjacent or contra-lateral area. A combination of
      characteristic painful symptoms in an area of altered sensation on bedside
      testing is usually enough to make a diagnosis of neuropathic pain. When doubt
      arises, more detailed examination using Quantitative Sensory Testing or
      conventional electrophysiology can be helpful.

PMID- 21882146
TI  - [Migraine - diagnostic features, acute therapy and prophylactics].
AB  - Migraine is a chronic. disabling, biologically determined, inherited brain
      disorder rendering life much less tolerable. The International Headache Society
      (IHS) offers guidelines for the classification and diagnosis of migraine
      headaches, in a document called 'The International Classification of Headache
      Disorders, 2nd edition' (ICHD-2). Migraine affects 10-16% of the population world
      wide. For the 20-30% of migraine sufferers who experience migraine with aura,
      this aura comprises focal neurological phenomena that precede or accompany the
      attack. There are three main aspects of treatment: trigger avoidance, acute
      symptomatic control, and pharmacological prevention. Acute medications are more
      effective if used earlier in an attack. The goals of preventive therapy are to
      reduce the frequency, painfulness, and/or duration of migraines, and to increase
      quality of life.

PMID- 21882147
TI  - [Operant and cognitive behavioural treatments in chronic pain].
AB  - In the present review learning procedures as operant and classical conditioning
      on the development of chronic pain as well as the influence of cognitive and
      affective factors will be reported. Characteristics of extinction and its
      applications in operant and cognitive behavioural treatment as well as its
      combination with pharmacological agents will be discussed. Operant and cognitive
      behavioural treatments were shown effective in treating chronic pain.
      Combinations with pharmacological agents have to be examined in future research.

PMID- 21882148
TI  - [Pharmacological treatment of chronic pain].
AB  - The pharmacological treatment of chronic pain differs from acute pain management.
      In chronic non-cancer pain patients pharmacological treatment is only one element
      of an interdisciplinary approach. Not pain reduction only but gain in physical
      and social functioning is mandatory for continuation of therapy. The
      developpement of a strategy is the most important and difficult step toward an
      individual and sustained pharmacological pain treatment. Simple practical
      guidelines can help to find an individual therapeutic straight. Outcome
      parameters have to be determined. Check-ups for discontinuation of the therapy
      have to be done periodically. Exact documentation of effect and side effects
      prevents ungrateful and potential dangerous treatments. The WHO ladder remains
      the cornerstone of pharmacological pain treatment. Further analgesics as
      antidepressants and anticonvulsants are important in treatment of neuropathic or
      mixed pain states. Special considerations have to be done in opioid treatment of
      non-cancer pain regarding the lack of evidence in long term outcome and possible
      side effects and risks.

PMID- 21882149
TI  - [Physiotherapy].
AB  - In this review the therapeutical options of physiotherapy in patients with
      chronic musculoskeletal pain, especially non-specific back pain, are reported.
      The importance of the objective "reduction of pain related disability of
      individual activities of daily living" is reported. Various methods of exercise
      therapy and their application in either a monodisciplinary setting or in an
      interdisciplinary pain management team are discussed.

PMID- 21882150
TI  - [Multidisciplinary rehabilitation programs].
AB  - This is an overview of development, aspects of content, importance and evidence
      of multidisciplinary rehabilitation programs. In subacute and chronic pain, bio
      psycho-social factors act together in a complex manner. The importance of multi
      modal treatment programs will, thus, be focused. However, present study data show
      only few positive effects in this field.

PMID- 21882151
TI  - [Interventional pain management, indications and results].
AB  - When conservative treatment modalities provide inadequate relief, interventional
      techniques play an important role in the management of chronic pain patients.
      They are performed in diagnostic or therapeutic intention (or both) and either
      directly target the pain generating anatomic structure (e.g. intraarticular joint
      injections) or the neural structures which are thought to mediate the experience
      of pain (e.g. facet joint nerve blocks, spinal cord stimulation). In order to
      enhance precision and patient safety, these interventions are performed with
      image guidance; of which fluoroscopy is the most commonly used technique. CT- or
      Ultrasound-guided techniques are also performed. This article is an overview of
      the indications and results of the most commonly performed interventional
      techniques used in chronic pain treatment with focus on spinal interventional
      procedures.

PMID- 21882152
TI  - [Early detection of psychoses- weighing risks and benefits in children and
      adolescents].

PMID- 21882153
TI  - [Early detection of psychosis in children and adolescents - have developmental
      particularities been sufficiently considered?].
AB  - The early detection and treatment of persons at risk for psychosis is currently
      regarded as a promising strategy in fighting the devastating consequences of
      psychotic disorders. The two current favored at-risk approaches, i.e., the "ultra
      high risk" and the "basic symptom" criteria, were developed mainly using adult
      samples. Initial evidence suggests, however, that they cannot simply be applied
      to children and adolescents. For "ultra-high risk" criteria, there is indication
      of some attenuated psychotic symptoms being potentially nonspecific in
      adolescents, and of brief limited intermittent symptoms being difficult to
      clinically classify in children when observable behavioral correlates are
      missing. For basic symptoms, too, only a preliminary indication of their
      usefulness in children and adolescents exists. Since developmental peculiarities
      in the assessment of basic symptoms should be considered, a child and youth
      version of the Schizophrenia Proneness Instrument (SPI-CY) was developed. In
      conclusion, research on the clinical-prognostic validity of the at-risk criteria
      and their potential adaption to the special needs of children and adolescents is
      needed. If a "Prodromal Risk Syndrome for Psychosis" or "Attenuated Psychotic
      Symptoms Syndrome" are included in the upcoming DSM-5, it should be highlighted
      that its suitability for children and adolescents is only insufficiently known.

PMID- 21882154
TI  - [Follow-up support measures as parameters for the effectiveness of day-care
      measures in youth welfare - a comparative study].
AB  - OBJECTIVE: Educational support measures aim at reducing strain on families in
      precarious life situations. In children and adolescents, measures usually focus
      on reducing conduct problems and promoting competencies; parents are supported in
      order to improve their parenting competencies. But youth welfare measures have
      different effects on children, adolescents, and their parents, and a national
      comparison reveals that most families require follow-up support measures
      afterwards. This study compares different courses of youth assistance measures in
      families with or without follow-up support measures. METHODS: A total of 89
      families received day-care educational support for an average period of 2 years.
      Subsequently, 26 families required further support. In order to identify
      predictors for follow-up support measures, we systematically assessed problem
      areas indicating a need for further support prior to and after youth help
      measures, and contrasted them in a pre-post-design. RESULTS: Children in need of
      further support displayed significantly more symptoms of strain and less
      improvement in their competencies after the end of youth help measures. However,
      the most distinctive differences resulted for ineffective parenting. These groups
      differed significantly. CONCLUSIONS: The effectiveness of youth welfare measures
      strongly depends on an improvement of parenting competencies. A lack thereof
      points toward further need for support, even after intensive educational support
      measures.

PMID- 21882155
TI  - [The Essen Trauma-Inventory for children and adolescents (ETI-CA)].
AB  - OBJECTIVE: In light of the clinical and scientific relevance of traumatic events
      and posttraumatic disorders our study aimed to develop and validate the Essen
      Trauma-Inventory for Children and Adolescents (ETI-CA). The new instrument should
      assess various aspects of traumatic events and both posttraumatic disorders,
      namely Posttraumatic Stress Disorder and Acute Stress Disorder according to the
      criteria provided in DSM-IV. METHOD: ETI-CA was administered to a sample
      consisting of 276 children and adolescents aged between 12 and 17 years with
      regard to psychometric properties on clinical and non-clinical groups. RESULTS:
      The ETI-CA subscales as well as the total score proved to have high internal
      consistency. The 4-factorial structure (intrusion, avoidance, hyperarousal,
      dissociation) was in line with the theoretical assumptions. Associations between
      ETI-CA and other trauma instruments as well as instruments for psychological
      distress and protective factors provided empirical evidence for the construct
      validity of ETI-CA. CONCLUSIONS: In German-speaking regions, the ETI-CA
      represents the first economic, reliable and valid screening instrument that
      assesses exposure to a broad range of potential traumatic events as well as
      posttraumatic disorders. The ETI-CA can be recommended for use in research as
      well as in clinical settings.

PMID- 21882156
TI  - [The effect of social and monetary reward on inhibitory control in boys with
      hyperkinetic conduct disorder].
AB  - OBJECTIVE: Social reinforcement can improve inhibitory control in boys with
      attention deficit/hyperactivity disorder (ADHD), suggesting that hyperkinetic
      conduct disorder (ADHD + CD/ODD), a combination of ADHD and conduct disorder
      (CD)/oppositional defiant disorder (ODD), might show similar improvements. This
      study investigated the effects of social and monetary reward on response
      inhibition in boys with ADHD + CD/ODD compared to healthy controls. METHOD: An
      incentive go/no-go task was applied. We hypothesized that the control group (n =
      17) would show greater improvements in inhibitory control in response to social
      reward than the ADHD + CD/ODD group (n = 17), but that both groups would respond
      equally to monetary reward. RESULTS: Both groups showed improved inhibition
      accuracy in the social condition and even greater improvement in the monetary
      condition. Interestingly, the control group altered their response strategy when
      money was at stake, i.e., they slowed down more dramatically in favour of
      stronger inhibitory control and, thus, a potentially greater financial gain.
      CONCLUSIONS: Our findings do not provide evidence for hyporesponsivity to social
      rewards in boys with ADHD + CD/ODD. Rather, our data suggest that both social and
      nonsocial reward procedures can be effective in behavioral interventions, but
      that monetary reinforcers may be more effective.

PMID- 21882157
TI  - Pervasive refusal syndrome. Three German cases provide further illustration.
AB  - Pervasive refusal syndrome (PRS) has been proposed as a new diagnostic entity
      among child and adolescent psychiatric disorders. It is characterized by a
      cluster of life-threatening symptoms including refusal of hood intake, decreased
      or complete lack of mobilization, and lack of communication as well as retreat
      from normal life activities. Active refusal to accept help as well as neglect of
      personal care have been core features of PRS in the limited number of cases
      reported in the last decade. There have, however; been cases with predominantly
      passive resistance, indicating the possibility that there may be a continuum from
      active refusal to passive resistance within PRS. Postulating this continuum
      allows for the integration of "depressive devitalization" -- a refusal syndrome
      mainly characterized by passive resistance -- into the concept of PRS. Here,
      three case vignettes of adolescent patients with PRS are presented. The patients'
      symptomatology can be allocated on this continuum of PRS. PRS and dissociative
      disorders are compared in greater detail and contrasted within this discussion of
      differential diagnoses at the poles of such a continuum. PRS is a useful
      diagnosis for cases involving symptoms of predominating refusal and retreat which
      cannot satisfactorily be classified by existing diagnostic categories, and which
      can mostly clearly be separated from dissociative disorder.

PMID- 21882160
TI  - Oxygen delivery.
AB  - Early recognition of failure of oxygen delivery and knowledge of how medications
      can alter oxygen delivery allow clinicians to institute appropriate therapies in
      a timely manner and can result in improved patient outcomes. Oxygen delivery can
      be estimated and evaluated using a variety of methods, including arterial blood
      gas sampling, blood lactate quantification, echocardiography, and direct cardiac
      output measurement. Delivery can be enhanced by manipulating the components of
      the oxygen delivery formula. Cardiac output, hemoglobin concentration, oxygen
      saturation, and oxygen tension can all be improved through therapeutic or
      pharmacologic intervention.

PMID- 21882161
TI  - Treating navicular syndrome in equine patients.
AB  - Navicular syndrome is a chronic, progressive condition affecting the navicular
      bone and bursa, deep digital flexor tendon (DDFT), and associated soft tissue
      structures composing the navicular apparatus. The treatment options for navicular
      syndrome are as varied as the proposed causes of the condition. The severity of
      clinical signs, intended use and workload of the horse, and owner compliance with
      therapy are important considerations in developing a treatment plan. Nonsurgical
      treatment of navicular syndrome consists of rest, hoof balance and corrective
      trimming/shoeing, and medical therapy, including administration of systemic
      antiinflammatories, hemorheologic medications, and intraarticular medications.
      While surgical therapy can include desmotomy of the collateral (suspensory)
      ligaments of the navicular bone, palmar digital neurectomy is more commonly
      performed when medical therapy is ineffective. Recently, adjunct therapies, such
      as acupuncture and extracorporeal shock wave therapy, have also been used to
      treat horses with navicular syndrome. Because of the wide range of pathologic
      changes and the lack of a definitive cure associated with navicular syndrome,
      treatment is directed toward the individual horse, focusing on the management of
      clinical signs to alleviate stress and retard degenerative changes of the
      navicular bursal and navicular regions.

PMID- 21882163
TI  - Nuclear scintigraphy in horses.
AB  - Nuclear scintigraphy has been used successfully for various applications in
      horses in the past 30 years. Many private practices and most veterinary schools
      have gamma cameras, which are used to image an injected radionuclide in an equine
      patient. Unique exercise-related demands place specific physiologic stressors on
      the musculoskeletal system of horses. Horses are often pushed beyond normal
      physiologic limits because of specific performance stresses; therefore, injury to
      their musculoskeletal system is common. Skeletal scintigraphy is exceedingly
      sensitive but relatively nonspecific for determining a definitive etiology.
      Equine scintigraphy is best suited for detecting acute soft tissue and osseous
      abnormalities because radiopharmaceutical uptake often precedes radiographic
      detection. However, scintigraphy can also be used to locate potential areas of
      abnormal osseous turnover in horses with chronic, vague lameness. This article
      reviews the basic principles of equine scintigraphy, with an emphasis on bone
      scintigraphy and the clinical applications of this technique. Vascular-, soft
      tissue-, and bone-phase acquisition are described along with basic image
      interpretation. Potential pitfalls in image acquisition and interpretation are
      discussed.

PMID- 21882164
TI  - Environmental enrichment for indoor cats.
AB  - Recommendations to cat owners to house their cats indoors confer the
      responsibility to provide conditions that ensure good health and welfare. Cats
      maintain their natural behaviors, such as scratching, chewing, and elimination,
      while living indoors, and they may develop health and behavior problems when
      deprived of appropriate environmental outlets for these behaviors. This article
      divides the environment into five basic "systems" to enable identification of
      features that may benefit from improvement. It also addresses practical means of
      meeting cats' needs in each of these systems.

PMID- 21882165
TI  - Arrhythmogenic right ventricular cardiomyopathy in boxers.
AB  - Arrhythmogenic right ventricular cardiomyopathy, formerly termed boxer
      cardiomyopathy, is a familial primary myocardial disease that is prevalent in
      boxers. Unique histopathologic changes in the myocardium lead to conduction
      abnormalities that typically manifest as ventricular tachyarrhythmias with left
      bundle branch block morphology. Affected dogs can be asymptomatic or may have
      syncope and/or exercise intolerance. Diagnosis can be difficult, and indications
      for antiarrhythmic therapy are not always clear. A small number of dogs present
      with systolic dysfunction and/or congestive heart failure. Screening in
      asymptomatic breeding dogs was difficult until the recent development of genetic
      testing.

PMID- 21882166
TI  - Feline thyroid storm: rapid recognition to improve patient survival.
AB  - In human medicine, thyroid storm is a well-recognized condition of acute
      thyrotoxicosis in which the patient's metabolic, thermoregulatory, and
      cardiovascular mechanisms are overwhelmed by excessive circulating levels of
      thyroid hormone. The etiology is unknown, but multiple precipitating factors have
      been proposed. Hyperthyroid cats presenting in thyrotoxic crisis have clinical
      signs similar to those of human thyroid storm patients; however, thyroid storm
      has not yet been fully characterized in veterinary medicine. Early recognition
      and prompt, appropriate treatment of this life-threatening condition are
      essential to obtaining a favorable outcome.

PMID- 21882167
TI  - Increase the success of weight loss programs by creating an environment for
      change.
AB  - Veterinary professionals frequently recommend weight loss programs for pets, but
      success is often elusive. By learning techniques to assess clients' readiness for
      change, the veterinary team can apply communication tools and strategies to help
      clients overcome obstacles and barriers to sustainable change. With a better
      assessment of a client's ability to change, a weight loss plan can be implemented
      at the right time in the right way to achieve better adherence to the agreed-upon
      plan and improve patient health.

PMID- 21882168
TI  - Canine anterior uveitis.
AB  - Canine anterior uveitis can be a debilitating, painful, vision-threatening
      disease. Several local and systemic diseases can cause anterior uveitis. Because
      the eye is limited in its ability to respond to injury, different diseases
      produce similar clinical signs, making an etiologic diagnosis difficult but
      imperative to improve the likelihood of a successful outcome. A thorough history
      and complete ocular and physical evaluations are necessary to ensure timely and
      accurate diagnosis. This article reviews the pathophysiology, most common causes,
      diagnostic recommendations, current therapeutic options, potential complications,
      and prognosis for canine anterior uveitis.

PMID- 21882169
TI  - Rheumatoid arthritis subgroup with type I interferon signature: comment on the
      article by Thurlings et al.

PMID- 21882170
TI  - Use of Oxyma as pH modulatory agent to be used in the prevention of base-driven
      side reactions and its effect on 2-chlorotrityl chloride resin.
AB  - The presence of low pKa N-hydroxylamines is beneficial in peptide chemistry as
      they reduce some base-mediated side reactions. Here we evaluated the
      applicability and buffering capacity of Ethyl 2-cyano-2-(hydroxyimino) acetate
      (Oxyma) in the prevention of aspartimide/piperidide formation and Pro-based
      overcoupling and compared it with the performance of HOBt and HOAt. In addition,
      the compatibility of these additives with the highly acid-labile 2-chlorotrityl
      chloride resin is examined.

PMID- 21882171
TI  - Review structure of silk by raman spectromicroscopy: from the spinning glands to
      the fibers.
AB  - Raman spectroscopy has long been proved to be a useful tool to study the
      conformation of protein-based materials such as silk. Thanks to recent
      developments, linearly polarized Raman spectromicroscopy has appeared very
      efficient to characterize the molecular structure of native single silk fibers
      and spinning dopes because it can provide information relative to the protein
      secondary structure, molecular orientation, and amino acid composition. This
      review will describe recent advances in the study of the structure of silk by
      Raman spectromicroscopy. A particular emphasis is put on the spider dragline and
      silkworm cocoon threads, other fibers spun by orb-weaving spiders, the spinning
      dope contained in their silk glands and the effect of mechanical deformation.
      Taken together, the results of the literature show that Raman spectromicroscopy
      is particularly efficient to investigate all aspects of silk structure and
      production. The data provided can lead to a better understanding of the structure
      of the silk dope, transformations occurring during the spinning process, and
      structure and mechanical properties of native fibers.

PMID- 21882172
TI  - Spectroscopic investigations to reveal the nature of interactions between the
      haem protein myoglobin and the dye rhodamine 6G.
AB  - In the present investigation, steady-state and time-resolved fluorescence with
      the combination of circular dichroism (CD) spectroscopic techniques were applied
      to study the interactions of the well-known dye rhodamine 6 G (R6G) with the haem
      protein human myoglobin (Mb). From the analysis of the results it appears that
      the static type of fluorescence quenching mechanism is primarily involved, due to
      ground-state interactions. Although considerable overlapping of fluorescence
      emission of the dye R6G with the absorption of Mb in the Q-band region exists,
      the possibility of occurrences of the excitational singlet-singlet non-radiative
      energy transfer process from R6G to Mb appears to be unlikely, according to time
      resolved fluorescence measurements. From the determinations of the thermodynamic
      parameters, it was apparent that the combined effect of van der Waals'
      interactions and hydrogen bonding plays a vital role in Mb-R6G interactions.
      Induced circular dichroism (ICD) studies demonstrate the possibility of
      interactions between R6G and Mb. The binding constants, number of binding sites
      and thermodynamic parameters have been computed. From CD measurements it is
      apparent that the binding of the dye R6G with the haem protein Mb induces
      negligible conformational changes in the protein and Mb retains its secondary
      structure and helicity when it interacts with R6G. The present detailed studies
      on the interactions with Mb should be helpful in further advancement of medical
      diagnostics and biotechnology.

PMID- 21882173
TI  - Critical conditions for ferric chloride-induced flocculation of freshwater algae.
AB  - The effects of algae concentration, ferric chloride dose, and pH on the
      flocculation efficiency of the freshwater algae Chlorella zofingiensis can be
      understood by considering the nature of the electrostatic charges on the algae
      and precipitate surfaces. Two critical conditions are identified which, when met,
      result in flocculation efficiencies in excess of 90% for freshwater algae. First,
      a minimum concentration of ferric chloride is required to overcome the
      electrostatic stabilization of the algae and promote bridging of algae cells by
      hydroxide precipitates. At low algae concentrations, the minimum amount of ferric
      chloride required increases linearly with algae concentration, characteristic of
      flocculation primarily through electrostatic bridging by hydroxide precipitates.
      At higher algae concentrations, the minimum required concentration of ferric
      chloride for flocculation is independent of algae concentration, suggesting a
      change in the primary flocculation mechanism from bridging to sweep flocculation.
      Second, the algae must have a negative surface charge. Experiments and surface
      complexation modeling show that the surface charge of C. zofingiensis is negative
      above a pH of 4.0 +/- 0.3 which agrees well with the minimum pH required for
      effective flocculation. These critical flocculation criteria can be extended to
      other freshwater algae to design effective flocculation systems.

PMID- 21882174
TI  - The N-domain of Escherichia coli phosphoglycerate kinase is a novel fusion
      partner to express aggregation-prone heterologous proteins.
AB  - As a fusion partner to express aggregation-prone heterologous proteins, we
      investigated the efficacy of Escherichia coli phosphoglycerate kinase (ePGK) that
      consists of two functional domains (N- and C-domain) and reportedly has a high
      structural stability. When the full-length ePGK (F-ePGK) was used as a fusion
      partner, the solubility of the heterologous proteins increased, but some of them
      still had a large fraction of insoluble aggregates. Surprisingly, the fusion
      expression using the N-domain of ePGK (N-ePGK) made the insoluble fraction
      significantly reduce to less than 10% for all the heterologous fusion proteins
      tested. Also, we evaluated the efficacy of N-ePGK in making the target proteins
      be expressed with their own native function or structure. It was found that of
      human ferritin light chain, bacterial arginine deiminase, human granulocyte
      colony stimulating factor were synthesized evidently with the self-assembly
      function, L-arginine-degrading activity, and the correct secondary structure,
      respectively, through the fusion expression using N-ePGK. These results indicate
      that N-ePGK is a highly potent fusion partner that can be widely used for the
      synthesis of a variety of heterologous proteins in E. coli.

PMID- 21882176
TI  - Randomized controlled trial of acitretin versus placebo in patients at high-risk
      for basal cell or squamous cell carcinoma of the skin (North Central Cancer
      Treatment Group Study 969251).
AB  - BACKGROUND: Chemoprevention with systemic retinoids has demonstrated promise in
      decreasing the incidence of new primary nonmelanoma skin cancers (NMSCs) in
      immunocompromised post-transplantation recipients. There is limited evidence for
      the use of systemic retinoids in the nontransplantation patient. To the authors'
      knowledge, this is the first randomized controlled trial to assess the efficacy
      of acitretin as a chemopreventive agent in nontransplantation patients at high
      risk for NMSC. METHODS: The study was designed as a prospective, randomized,
      double-blind, placebo-controlled clinical trial. To test the possible skin cancer
      preventing effect of a 2-year treatment with acitretin, 70 nontransplantation
      patients aged >=18 years who had a history of >=2 NMSCs within 5 years of trial
      onset were randomized to receive either placebo or acitretin 25 mg orally 5 days
      per week. The primary outcome measure was the rate of new NMSC development.
      RESULTS: Seventy patients were randomized to receive either acitretin alone (N =
      35) or placebo (N = 35). During the 2-year treatment period, the patients who
      received acitretin did not have a statistically significant reduction in the rate
      of new primary NMSCs (odds ratio, 0.41; 95% confidence interval, 0.15-1.13; 54%
      vs 74%; P = .13). However, using the incidence of new NMSC, the time to new NMSC,
      and total NMSC counts, an umbrella test indicated a significant trend that
      favored the use of acitretin (chi-square statistic, 3.94; P = .047). The patients
      who received acitretin reported significantly more mucositis and skin toxicities
      compared with the patients who received placebo. CONCLUSIONS: Although there was
      not a statistically significant benefit observed with the use of acitretin, this
      may have been the result of low statistical power.

PMID- 21882177
TI  - A combined molecular-pathologic score improves risk stratification of thyroid
      papillary microcarcinoma.
AB  - BACKGROUND: Thyroid papillary microcarcinoma (TPMC) is an incidentally discovered
      papillary carcinoma that measures <=1.0 cm in size. Most TPMCs are indolent,
      whereas some behave aggressively. The objective of the study was to evaluate
      whether the combination of v-raf murine sarcoma viral oncogene homolog B1 (BRAF)
      mutation and specific histopathologic features allows risk stratification of
      TPMC. METHODS: A group aggressive TPMCs was selected based on the presence of
      lymph node metastasis or tumor recurrence. Another group of nonaggressive tumors
      included TPMCs matched with the first group for age, sex, and tumor size, but
      with no extrathyroid spread. A molecular analysis was performed, and histologic
      slides were scored for multiple histopathologic criteria. A separate validation
      cohort of 40 TPMCs was evaluated. RESULTS: BRAF mutations were detected in 77% of
      aggressive TPMCs and in 32% of nonaggressive tumors (P = .001). Several
      histopathologic features differed significantly between the groups. By using
      multivariate regression analysis, a molecular-pathologic (MP) score was developed
      that included BRAF status and 3 histopathologic features: superficial tumor
      location, intraglandular tumor spread/multifocality, and tumor fibrosis. By
      adding the histologic criteria to BRAF status, sensitivity was increased from 77%
      to 96%, and specificity was increased from 68% to 80%. In the independent
      validation cohort, the MP score stratified tumors into low-risk, moderate-risk,
      and high-risk groups with the probability of lymph node metastases or tumor
      recurrence in 0%, 20%, and 60% of patients, respectively. CONCLUSIONS: BRAF
      status together with several histopathologic features allowed clinical risk
      stratification of TPMCs. The combined MP risk stratification model was a better
      predictor of extrathyroid tumor spread than either mutation or histopathologic
      findings alone.

PMID- 21882178
TI  - Prognostic value of MYC rearrangement in cases of B-cell lymphoma,
      unclassifiable, with features intermediate between diffuse large B-cell lymphoma
      and Burkitt lymphoma.
AB  - BACKGROUND: B-cell lymphoma, Unclassifiable with features intermediate between
      diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma, for convenience
      referred to here as unclassifiable B-cell lymphoma, is a category in the 2008
      World Health Organization system used for a group of histologically aggressive
      neoplasms that are difficult to classify definitively. Currently, there is no
      established standard therapy for these neoplasms. METHODS: The authors assessed
      MYC status and correlated it with treatment response and outcome in a group of 52
      patients with unclassifiable B-cell lymphoma treated with either a standard DLBCL
      regimen (R-CHOP [rituximab plus cyclophosphamide, doxorubicin, vincristine, and
      prednisolone-related therapy]) or more intensive regimens, such as R-hyper-CVAD
      (rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and
      dexamethasone alternating with high-dose methotrexate and cytarabine). The
      regimens were selected by the treating clinicians based on the overall clinical
      and pathological findings. RESULTS: Thirty (58%) unclassifiable B-cell lymphomas
      had MYC abnormalities (MYC(+) ) including 27 with rearrangement, 2 with
      amplification, and 1 with both. The MYC(+) and MYC(-) groups were similar in
      their age distribution and International Prognostic Index scores. Progression
      free survival of patients with MYC(+) unclassifiable B-cell lymphoma treated
      initially with R-CHOP was significantly worse than patients treated with R-hyper
      CVAD (P = .0358). In contrast, for the MYC(-) unclassifiable B-cell lymphoma
      group, some patients responded to R-CHOP, and others were refractory to R-hyper
      CVAD. CONCLUSIONS: MYC aberrations are common in unclassifiable B-cell lymphoma.
      The presence of MYC aberrations identifies a patient subset that requires more
      aggressive therapy than R-CHOP. In contrast, MYC(-) unclassifiable B-cell
      lymphoma patients responded variably to either R-CHOP or aggressive therapy, and
      the latter showed no survival advantage.

PMID- 21882179
TI  - Influence of socioeconomic status and hospital type on disparities of lymph node
      evaluation in colon cancer patients.
AB  - BACKGROUND: A minimum of 12 dissected lymph nodes (LNs) has been recommended as a
      consensus guideline for resections in colon cancer patients. This study assessed
      the influence of both socioeconomic status (SES) and hospital type on compliance
      with this colon LN dissection guideline and examined the time trend for >=12 LNs
      dissected. METHODS: Stage I to III incident colon cancer cases diagnosed from
      1996 to 2007 were obtained from the Louisiana Tumor Registry. A composite census
      tract-level SES score was created to serve as a surrogate for individual-level
      SES. Hospitals performing colon resections were categorized into 5 groups
      according to the Commission on Cancer Accreditation Program. Multiple logistic
      regression analyses were used. RESULTS: Of 10,460 colon cancer cases diagnosed
      during the study period, 43.9% had >=12 LNs dissected. Patients residing in less
      affluent SES areas were less likely to receive a dissection of >=12 nodes than
      those residing in more affluent areas. SES was no longer significant after
      adjusting for race, sex, age, stage, grade, anatomic subsite, diagnosis year, and
      hospital type. In contrast, hospital type was significantly associated with the
      number of LNs dissected, even after adjusting for other factors. Patients
      diagnosed from 2002 to 2007 were twice as likely (95% confidence interval, 1.84
      2.17) to have >=12 LNs dissected than those diagnosed from 1996 to 2001 after
      adjustment. CONCLUSIONS: In Louisiana, hospital type is an independent
      significant predictor of adequate LN evaluation for colon cancer. Training and
      education are needed to reduce this disparity in the facilities with consistently
      lower LN yield in their dissections.

PMID- 21882180
TI  - Pretreatment and routine echocardiogram monitoring during chemotherapy for
      anthracycline-induced cardiotoxicity rarely identifies significant cardiac
      dysfunction or alters treatment decisions: a 5-year review at a single pediatric
      oncology center.
AB  - BACKGROUND: The widespread use of anthracycline chemotherapy has contributed to
      improved outcomes in children with cancer. The most feared complication of the
      anthracyclines is cardiotoxicity. Routine echocardiographic monitoring typically
      is used before, during, and after treatment to minimize cardiotoxicity. The ideal
      use of screening before and during chemotherapy remains uncertain. METHODS: This
      was a retrospective review of children who were treated at a single cancer
      treatment center over 5 years. The results of all echocardiograms and related
      clinical decisions were reviewed. RESULTS: In 356 patients who were identified
      for review (age range, 3 months to 22 years; mean age, 10 years; median age, 11
      years), 991 echocardiograms were reviewed (average, 2.78 echocardiograms per
      patient; median, 2 echocardiograms per patient; mode, 1; maximum, 11
      echocardiograms per patient). Nine abnormal echocardiograms were identified (2.5%
      of patients and 0.9% of echocardiograms performed). Four echocardiograms were
      performed during episodes of septic shock, 2 echocardiograms represented false
      positive studies after repeat evaluation, and 1 echocardiogram demonstrated mild
      abnormality of function on the day of surgical resection of a large Wilms tumor.
      None of the 356 pretreatment echocardiograms altered treatment decisions. In 635
      follow-up echocardiograms during treatment, cardiac defects were detected in 2
      patients (0.5%). CONCLUSIONS: The routine use of echocardiograms to screen for
      anthracycline-induced cardiac damage before and during chemotherapy rarely
      identified significant cardiac damage to impact treatment decisions. Improved
      screening techniques with better discrimination and predictability are needed.
      Pediatric Oncology cooperative groups should consider a revision of standard
      monitoring protocols before and during treatment.

PMID- 21882181
TI  - Association of VEGF and VEGFR2 single nucleotide polymorphisms with hypertension
      and clinical outcome in metastatic clear cell renal cell carcinoma patients
      treated with sunitinib.
AB  - PURPOSE: Biomarkers that predict response or toxicity to antiangiogenic therapy
      are sought to favorably inform the risk/benefit ratio. This study evaluated the
      association of vascular endothelial growth factor (VEGF) and VEGF receptor 2
      (VEGFR2) genetic polymorphisms with the development of hypertension (HTN) and
      clinical outcome in metastatic clear cell renal cell carcinoma (MCCRCC) patients
      treated with sunitinib. PATIENT AND METHODS: Sixty-three MCCRCC patients
      receiving sunitinib (50 mg 4/2) with available blood pressure (BP) data and
      germline DNA were retrospectively identified. A panel of candidate VEGF and
      VEGFR2 single nucleotide polymorphisms (SNPs) were evaluated for associations
      with the development of hypertension and clinical outcome. RESULTS: VEGF SNP -634
      genotype was associated with the prevalence and duration of sunitinib-induced
      hypertension (as defined by systolic pressure >=150 mmHg and/or diastolic
      pressure >=90 mmHg) in both univariable analysis (P = .03 and .01, respectively)
      and multivariable analysis, which adjusted for baseline BP and use of
      antihypertension medication (P = .05 and .02, respectively). Patients with the GG
      genotype were estimated to have a greater likelihood of being hypertensive during
      treatment compared with patients with the CC genotype (odds ratio of 13.62, 95%
      confidence interval [CI] 3.71-50.04). No single VEGF or VEGFR SNPs were found to
      correlate with clinical outcome. However, the combination of VEGF SNP 936 and
      VEGFR2 SNP 889 were associated with overall survival after adjustment for
      prognostic risk group (P = .03). CONCLUSIONS: In MCCRCC patients treated with
      sunitinib, VEGF SNP -634 is associated with hypertension and a combination of
      VEGF SNP 936 and VEGFR2 SNP 889 genotypes is associated with overall survival.

PMID- 21882182
TI  - Adjuvant chemotherapy improves survival in patients with American Joint Committee
      on Cancer stage II colon cancer.

PMID- 21882183
TI  - Adult glioblastoma multiforme survival in the temozolomide era: a population
      based analysis of Surveillance, Epidemiology, and End Results registries.
AB  - BACKGROUND: Survival after a glioblastoma multiforme (GBM) diagnosis remained
      static during the several decades before 1999. We hypothesized that the
      progressive increase in temozolomide use for GBM treatment that began in 1999 in
      the United States would be paralleled by a corresponding improvement in survival.
      METHODS: We included 19,674 GBM cases, ages 20 years or greater, diagnosed 1993
      to 2007 in the population-based Surveillance, Epidemiology, and End Results
      Program database. We used proportional hazards models to calculate calendar
      period hazard ratios (HR) and 95% confidence intervals (CI), adjusted for
      demographic covariates. We compared survival across periods using the Kaplan
      Meier method. RESULTS: Starting with cases diagnosed in 1999 to 2001, we observed
      a progressive decrease in HRs compared with cases diagnosed in 1993 to 1995. The
      multivariate-adjusted HR for 2005 to 2007 versus 1993 to 1995 was 0.69 (95% CI,
      0.65-0.72). Age-stratified analyses revealed that this progressive decrease
      occurred in all age groups except 80+ years. Two-year survival increased from 7%
      among cases diagnosed in 1993 to 1995 and 1996 to 1998 to 9% among cases
      diagnosed in 1999 to 2001, 13% in 2002 to 2004, and 17% in 2005 to 2007. The
      disparity in survival between young and old patients increased in the
      temozolomide era, with 2-year survival of 39% among cases diagnosed at ages 20 to
      44 years and 1% among cases diagnosed at 80+ years in 2005 to 2007. CONCLUSIONS:
      We observed a modest, but meaningful, population-based survival improvement for
      GBM patients in the United States. Widespread adoption of temozolomide represents
      the most likely explanation, although other treatment advances, such as increased
      extent of surgical resection, also may have played a role.

PMID- 21882184
TI  - The association of the BRAF(V600E) mutation with prognostic factors and poor
      clinical outcome in papillary thyroid cancer: a meta-analysis.
AB  - BACKGROUND: The effects of the BRAF(V600E) mutation on prognostic factors and
      poor clinical outcomes in papillary thyroid cancer (PTC) have not been fully
      quantified. The authors performed comprehensive meta-analysis to assess the
      strength of associations between these conditions and the BRAF(V600E) mutation.
      METHODS: The authors identified the clinical studies that examined the
      association of the BRAF(V600E) mutation in surgical specimens with
      clinicopathologic outcomes between January 2003 and October 2010 using the
      Medline database. One hundred thirty-one relevant studies were hand-searched. The
      authors selected 27 studies that included 5655 PTC patients. They calculated the
      pooled odds ratios (ORs) or risk ratios with 95% confidence intervals (CIs) for
      each study using a random effect model. RESULTS: The average prevalence rate of
      the BRAF(V600E) mutation was 49.4%. In 26 studies, compared with the patients who
      had the wild-type BRAF genes, the PTC patients with the BRAF(V600E) mutation had
      increased ORs of an extrathyroidal invasion (OR, 2.14; 95% CI, 1.68-2.73), a
      lymph node metastasis (OR, 1.54; 95% CI, 1.21-1.97), and an advanced TNM stage
      (OR, 2.00; 95% CI, 1.61-2.49). In 8 studies, patients with the mutation had 2.14
      fold increased risk of recurrent and persistent disease (95% CI, 1.67-2.74). The
      associations were generally consistent across the different study populations.
      CONCLUSIONS: This meta-analysis demonstrates that the BRAF(V600E) mutation is
      closely related to the high-risk clinicopathological factors and poorer outcome
      of PTC. The results obtained here suggest that the BRAF(V600E) mutation should be
      considered as a poor prognostic marker in PTC and may lead to better management
      for individual patients.

PMID- 21882186
TI  - Radiation field design and regional control in sentinel lymph node-positive
      breast cancer patients with omission of axillary dissection.
AB  - BACKGROUND: Randomized data suggest that axillary clearance is not necessary in
      select, clinically lymph node-negative women with positive sentinel lymph node
      (SLN) biopsies (SLNBs) who undergo breast-conserving surgery or receive whole
      breast radiotherapy and systemic therapy. The additional value of axillary
      radiotherapy in these patients is unknown. METHODS: The authors identified 326
      patients with positive SLNBs who underwent breast-conserving surgery without
      axillary lymph node dissection from 1997 to 2009. SLN tumor deposits measured
      <=0.2 mm in 58% of patients, 0.3 to 2.0 mm in 35% of patients, and >2 mm in 7%
      Patients. Ninety-three percent of patients received adjuvant radiotherapy.
      Radiation fields were categorized as standard tangents, high tangents,
      comprehensive (tangents plus supraclavicular), or partial breast to reflect
      coverage of the axilla. Standard tangents included both prone and supine
      positions. Regional failure was defined as recurrence in the ipsilateral
      supraclavicular, axillary, or internal mammary lymph nodes. RESULTS: The median
      follow-up was 55 months (range, 1-158 months). The 4-year rates of regional
      control, local control, disease-free survival, and overall survival were 99%,
      98%, 95%, and 91%, respectively. Three patients had regional recurrences. Two of
      those patients received adjuvant radiotherapy with standard supine tangents, and
      1 patient did not receive radiotherapy. No regional recurrences occurred among 66
      patients who received radiotherapy in the prone position. CONCLUSIONS: Regional
      control was high (99% at 4 years) in patients who had low-volume SLN disease who
      did not undergo axillary dissection, regardless of whether the axilla was
      irradiated. Whole-breast radiation alone, including in the prone position, is
      sufficient treatment after breast-conserving surgery for select patients with
      tumor-containing SLNs who omit axillary dissection.

PMID- 21882187
TI  - The preTCR-dependent DN3 to DP transition requires Notch signaling, is improved
      by CXCL12 signaling and is inhibited by IL-7 signaling.
AB  - The requirement for Notch signaling during T-cell development has been
      extensively studied. Nevertheless, the developmental stage at which it is
      required and whether additional signaling pathways are needed are still poorly
      understood. By using a stromal-cell-free culture system, we show that sorted
      double-negative 3 (DN3) thymocytes only require a Delta-like-4-induced Notch
      signal to differentiate into double-positive (DP) cells. This differentiation
      process is preTCR-alpha dependent. DN3 cells undergo 4-5 proliferation cycles,
      and the addition of the chemokine CXCL12 improves proliferation. IL-7 blocks the
      differentiation of DN3 cells to DP cells but not the Notch-induced proliferation
      of cultured DN3 cells. The impaired differentiation correlates with an inhibition
      of Rag-2 up-regulation. Overall, the in vitro stromal-cell-free culture system
      presented here also provides a powerful and unique tool for studying the
      mechanisms involved in the positive and negative selection of T cells.

PMID- 21882188
TI  - Cysteine-rich protein 1 is regulated by transforming growth factor-beta1 and
      expressed in lung fibrosis.
AB  - Transforming growth factor-beta (TGF-beta) is a diverse cytokine regulating
      growth, apoptosis, differentiation, adhesion, invasion, and extracellular matrix
      production. Dysregulation of TGF-beta is associated with fibrotic disorders and
      epithelial-mesenchymal transition, and has been linked with idiopathic pulmonary
      fibrosis (IPF). Cysteine-rich protein 1 (CRP1) is a small LIM-domain containing
      protein involved in smooth muscle differentiation. Here, we show that TGF-beta1
      increases the expression of CRP1 protein and that CRP1 levels increase in a
      biphasic fashion. A rapid transient (15-45 min) increase in CRP1 is followed by a
      subsequent, sustained increase in CRP1 a few hours afterwards that lasts several
      days. We find that TGF-beta1 regulates the expression of CRP1 through Smad and
      non-conventional p38 MAPK signaling pathways in a transcription-independent
      manner and that the induction occurs concomitant with an increase in
      myofibroblast differentiation. Using CRP1 silencing by shRNA, we identify CRP1 as
      a novel factor mediating cell contractility. Furthermore, we localize CRP1 to
      fibroblastic foci in IPF lungs and find that CRP1 is significantly more expressed
      in IPF as compared to control lung tissue. The results show that CRP1 is a novel
      TGF-beta1 regulated protein that is expressed in fibrotic lesions and may be
      relevant in the IPF disease.

PMID- 21882189
TI  - CD73-generated adenosine promotes osteoblast differentiation.
AB  - CD731 is a GPI-anchored cell surface protein with ecto-5'-nucleotidase enzyme
      activity that plays a crucial role in adenosine production. While the roles of
      adenosine receptors (AR) on osteoblasts and osteoclasts have been unveiled to
      some extent, the roles of CD73 and CD73-generated adenosine in bone tissue are
      largely unknown. To address this issue, we first analyzed the bone phenotype of
      CD73-deficient (cd73(-/-)) mice. The mutant male mice showed osteopenia, with
      significant decreases of osteoblastic markers. Levels of osteoclastic markers
      were, however, comparable to those of wild-type mice. A series of in vitro
      studies revealed that CD73 deficiency resulted in impairment in osteoblast
      differentiation but not in the number of osteoblast progenitors. In addition,
      over expression of CD73 on MC3T3-E1 cells resulted in enhanced osteoblastic
      differentiation. Moreover, MC3T3-E1 cells expressed adenosine A(2A) receptors
      (A(2A)AR) and A(2B) receptors (A(2B)AR) and expression of these receptors
      increased with osteoblastic differentiation. Enhanced expression of osteocalcin
      (OC) and bone sialoprotein (BSP) observed in MC3T3-E1 cells over expressing CD73
      were suppressed by treatment with an A(2B)AR antagonist but not with an A(2A) AR
      antagonist. Collectively, our results indicate that CD73 generated adenosine
      positively regulates osteoblast differentiation via A(2B)AR signaling.

PMID- 21882190
TI  - High glucose-induced repression of RAR/RXR in cardiomyocytes is mediated through
      oxidative stress/JNK signaling.
AB  - The biological actions of retinoids are mediated by nuclear retinoic acid
      receptors (RARs) and retinoid X receptors (RXRs). We have recently reported that
      decreased expression of RARalpha and RXRalpha has an important role in high
      glucose (HG)-induced cardiomyocyte apoptosis. However, the regulatory mechanisms
      of HG effects on RARalpha and RXRalpha remain unclear. Using neonatal
      cardiomyocytes, we found that ligand-induced promoter activity of RAR and RXR was
      significantly suppressed by HG. HG promoted protein destabilization and serine
      phosphorylation of RARalpha and RXRalpha. Proteasome inhibitor MG132 blocked the
      inhibitory effect of HG on RARalpha and RXRalpha. Inhibition of intracellular
      reactive oxidative species (ROS) abolished the HG effect. In contrast, H(2)O(2)
      stimulation suppressed the expression and ligand-induced promoter activity of
      RARalpha and RXRalpha. HG promoted phosphorylation of ERK1/2, JNK and p38 MAP
      kinases, which was abrogated by an ROS inhibitor. Inhibition of JNK, but not ERK
      and p38 activity, reversed HG effects on RARalpha and RXRalpha. Activation of JNK
      by over expressing MKK7 and MEKK1, resulted in significant downregulation of
      RARalpha and RXRalpha. Ligand-induced promoter activity of RARalpha and RXRalpha
      was also suppressed by overexpression of MEKK1. HG-induced cardiomyocyte
      apoptosis was potentiated by activation of JNK, and prevented by all-trans
      retinoic acid and inhibition of JNK. Silencing the expression of RARalpha and
      RXRalpha activated the JNK pathway. In conclusion, HG-induced oxidative stress
      and activation of the JNK pathway negatively regulated expression/activation of
      RAR and RXR. The impaired RAR/RXR signaling and oxidative stress/JNK pathway
      forms a vicious circle, which significantly contributes to hyperglycemia induced
      cardiomyocyte apoptosis.

PMID- 21882192
TI  - Human keratinocytes respond to direct current stimulation by increasing
      intracellular calcium: preferential response of poorly differentiated cells.
AB  - A direct current (DC) endogenous electric field (EF) is induced in the wound
      following skin injury. It is potentially implicated in the wound healing process
      by attracting cells and altering their phenotypes as indicated by the response to
      an EF of keratinocytes cultured as individual cells. To better define the
      signalization induced by a direct current electric field (DCEF) in human
      keratinocytes, we took advantage of an in vitro model more representative of the
      in vivo situation since it promotes cell-cell interactions and stratification.
      Human keratinocytes were grown into colonies. Their exposure to a DCEF of
      physiological intensity induced an increase of intracellular calcium. This
      variation of intracellular calcium resulted from an extracellular calcium influx
      and was mediated, at least in part, by the L-type voltage-gated calcium channel.
      The increase in intracellular calcium in response to a DCEF was however not
      observed in all the cells composing the colonies. The intracellular calcium
      increase was only detected in keratinocytes that didn't express involucrin, a
      marker of differentiated cells. These results indicate that DCEF is able to
      induce a specific calcium response in poorly differentiated keratinocytes. This
      study brings a new perspective for the understanding of the signaling mechanism
      of endogenous EF in reepithelialization, a critical process during skin wound
      healing.

PMID- 21882191
TI  - Development and characterization of an organotypic model of Barrett's esophagus.
AB  - Understanding the molecular and cellular processes underlying the development,
      maintenance, and progression of Barrett's esophagus (BE) presents an empirical
      challenge because there are no simple animal models and standard 2D cell culture
      can distort cellular processes. Here we describe a three-dimensional (3D) cell
      culture system to study BE. BE cell lines (CP-A, CP-B, CP-C, and CP-D) and
      esophageal squamous keratinocytes (EPC2) were cultured on a matrix consisting of
      esophageal fibroblasts and collagen. Comparison of growth and cytokeratin
      expression in the presence of all-trans retinoic acid or hydrochloric acid was
      made by immunohistochemistry and Alcian Blue staining to determine which
      treatments produced a BE phenotype of columnar cytokeratin expression in 3D
      culture. All-trans retinoic acid differentially affected the growth of BE cell
      lines in 3D culture. Notably, the non-dyplastic metaplasia-derived cell line (CP
      A) expressed reduced squamous cytokeratins and enhanced columnar cytokeratins
      upon ATRA treatment. ATRA altered the EPC2 squamous cytokeratin profile towards a
      more columnar expression pattern. Cell lines derived from patients with high
      grade dysplasia already expressed columnar cytokeratins and therefore did not
      show a systematic shift toward a more columnar phenotype with ATRA treatment.
      ATRA treatment, however, did reduce the squamoid-like multilayer stratification
      observed in all cell lines. As the first study to demonstrate long-term 3D growth
      of BE cell lines, we have determined that BE cells can be cultured for at least 3
      weeks on a fibroblast/collagen matrix and that the use of ATRA causes a general
      reduction in squamous-like multilayered growth and an increase in columnar
      phenotype with the specific effects cell-line dependent.

PMID- 21882193
TI  - Implementation of educational video improves patient understanding of basic
      breast cancer concepts in an undereducated county hospital population.
AB  - BACKGROUND: The purpose of this study was to evaluate the effect of a video on
      patient understanding of basic breast cancer concepts. METHODS: An 11 item tool
      of breast cancer concepts was devised. A previous study obtained baseline
      information on patient knowledge. Subsequently an 8 min video was designed to
      facilitate the understanding of these concepts. The next 40 consecutive patients
      who saw the video were then administered the same 11 item questionnaire. RESULTS:
      Eighty-one women agreed to participate in the study, 41 before and 40 after the
      implementation of the video. Fifty-one percent had less than a high school
      education. The group who saw the video had a higher mean number of questions
      correct (6.7 vs. 8.9, P = 0.0007). Interestingly 90% of all respondents correctly
      answered the question on the value of screening mammography, however, only 37% of
      these patients underwent screening mammograms. A multiple linear regression model
      adjusting for years of education, language, and seeing the video, revealed that
      having seen the video (P = 0.0029) and years of education (P = 0.0002) remained
      significantly associated with higher score. CONCLUSIONS: Implementation of an
      educational video significantly improved understanding of breast cancer concepts
      in an undereducated population.

PMID- 21882194
TI  - Intraperitoneal docetaxel combined with S-1 for advanced gastric cancer with
      peritoneal dissemination.
AB  - BACKGROUND: Our previous phase I study indicated that combination chemotherapy
      with intraperitoneal docetaxel and S-1 was well tolerated by gastric cancer
      patients with peritoneal carcinomatosis (PC). This study evaluated the benefits
      of this combination chemotherapy and subsequent surgery. PATIENTS AND METHODS:
      Neoadjuvant Intra-Peritoneal and Systemic chemotherapy (NIPS) was introduced to
      gastric cancer patients with positive cytology or with PC. Two cycles of
      intraperitoneal chemotherapy with docetaxel combined with S-1, were administrated
      and gastrectomy with lymph node dissection was performed in cases without
      macroscopic PC at post-NIPS staging laparoscopy. RESULTS: Eighteen patients were
      enrolled in this study. Eight patients had measurable lymph node metastases by
      the RECIST criteria and computed tomography (CT) showed that five (62.5%)
      displayed a major response to the treatment. Out of 18 patients, 14 (78%) showed
      negative results on peritoneal cytology and no macroscopic PC, while the
      remaining four were cancer cell positive on peritoneal cytology or showed
      macroscopic PC even after NIPS. The median survival time of the entire group was
      24.6 months. No treatment-related mortality was observed during NIPS and surgery.
      CONCLUSION: This study indicated that the NIPS combined with surgery was highly
      active and well tolerated by advanced gastric cancer patients with PC.

PMID- 21882195
TI  - The impact of recurrent laryngeal neuromonitoring on multi-dimensional voice
      outcomes following thyroid surgery.
AB  - BACKGROUND: Voice changes after thyroidectomy are common but not always related
      to recurrent laryngeal nerve (RLN) injury. We evaluated if RLN neuromonitoring
      correlated with non-RLN injury-related changes in voice after thyroidectomy.
      METHODS: Prospective multi-dimensional voice assessment was conducted on patients
      undergoing thyroidectomy before, 1-4 weeks, and 6 months postoperatively. Voice
      outcome (VO) was determined as normal (NormVO) or negative (NegVO) based upon
      combinations of patient-reported symptoms, videolaryngoscopy, a composite of
      acoustic measurements, and clinician-perceived voice quality. Groups with and
      without neuromonitoring were compared for early and durable differences in VO.
      RESULTS: Ninety-one patients underwent thyroidectomy; 39 with RLN neuromonitoring
      and 52 without. The two study groups were similar with regard to baseline
      characteristics including voice assessment. There was no difference in NegVO
      between neuromonitored and non-monitored patients at 1-4 weeks (n = 89; 32% vs.
      27%; P = 0.81) and 6 months (n = 71, 14% vs. 7%; P = 0.42) after thyroidectomy.
      Neuromonitoring was associated with a 48-min increase in median operative time,
      but this finding was not statistically significant in a multivariate model.
      CONCLUSION: In this study, recurrent laryngeal neuromonitoring did not appear to
      influence non-RLN injury related VO as measured by a comprehensive
      multidimensional voice assessment.

PMID- 21882196
TI  - MiR-142-3p as a potential prognostic biomarker for esophageal squamous cell
      carcinoma.
AB  - BACKGROUND AND OBJECTIVES: microRNAs (miRNAs), small non-coding RNAs, are always
      aberrantly expressed in many diseases including human cancers. The aim of this
      study was to examine and determine the clinical significance of hsa-miR-31, hsa
      miR-142-3p, hsa-miR-338-3p, and hsa-miR-1261 expression in esophageal squamous
      cell carcinoma (ESCC). METHODS: Expression levels of four selected miRNAs,
      initially evaluated by microarray, were validated by qRT-PCR. Various statistical
      methods were used to analyze the relationship between miRNA expression and
      clinicopathologic features and prognosis in 91 patients with ESCC. RESULTS: MiR
      31 and miR-142-3p expression were correlated to histological differentiation in
      ESCC (P < 0.05, Student's t-test); high miR-142-3p expression was associated with
      a poor prognosis in all 91 ESCC patients (P = 0.014, log-rank) and identified as
      an independent prognostic factor in ESCC (P = 0.017, univariate Cox; P = 0.022,
      multivariate Cox). More importantly, stratified analysis indicated that high miR
      142-3p expression was correlated to a poor prognosis within good-prognosis groups
      comprised of ESCC patients with small tumor size, negative lymph node metastasis,
      or early stage (all P < 0.05). CONCLUSION: The main findings suggest that miR-142
      3p is involved in the progression of ESCC and is a potential prognostic biomarker
      for ESCC.

PMID- 21882198
TI  - High rate of solitary sentinel node metastases identification by fluorescence
      guided lymphatic imaging in breast cancer.
AB  - BACKGROUND: The lymph node status was shown to be an important prognostic factor
      for breast cancer, but controversial issues remain. There has been increased
      focus on optimizing the visualization of lymph nodes for an accurate and
      selective approach to axillary lymph nodes. Fluorescence-guided lymphatic imaging
      is a potential candidate for further research on remaining controversies.
      METHODS: Forty-seven patients were subject to injection of indocyanine green for
      navigation to the SLN based on fluorescent dye retention detection. In two
      groups, patients either received intended axillary lymph node dissection (ALND)
      and sentinel lymph node biopsy (SLNB) for superstaging or isolated SLNB for
      minimal-invasive staging. The prospective study was designed to evaluate the
      technical feasibility with focus on solitary positive SLN. RESULTS: Visualization
      of lymphatic vessels with bright fluorescence of the SLN was feasible in 46 of 47
      patients. Eighteen of 19 nodal positive patients were correctly identified with a
      sensitivity of 94.7% in all patients after ALND. After immunohistochemistry, in
      19 of 25 overall nodal positive patients (76%) the SLN was the only positive
      lymph node. CONCLUSION: Fluorescence-guided imaging using fluorescence retention
      detection allows transcutaneous navigation with a high rate of solitary positive
      SLN identification as an alternative technique for further research.

PMID- 21882197
TI  - Six primary cancers in one Lynch syndrome patient with chronic arsenic exposure.

PMID- 21882199
TI  - Is a level III dissection necessary for a positive sentinel lymph node in
      melanoma?
AB  - BACKGROUND: For melanoma patients with a positive axillary SLN, the extent of
      ALND remains controversial, with debate over whether a level III dissection is
      needed. METHODS: We queried our IRB approved prospective database for patients
      with a positive axillary SLN who had a level I/II dissection only, and compared
      recurrence and complication rates to the existing literature. RESULTS: Between
      1998 and 2008, 270 patients had 285 level I/II ALNDs for a positive SLN. Median
      number of SLN removed was 2, while the median number of involved SLN was 1 (range
      1-4). An average of 18.7 nodes/ALND were removed, with 13% having positive non
      SLN. Post-operative complications occurred in 31 patients (11%), primarily
      cellulitis (8%). After a mean follow-up of 44 months, 14 patients had a regional
      recurrence in the axillary basin (5%). CONCLUSIONS: The complication rate and
      regional recurrence rate for patients undergoing a level I/II ALND for a positive
      SLN are either lower than or on par with reported series of ALND for level I, II,
      and III dissections, suggesting that in this setting, the level III dissection
      may be of minimal benefit.

PMID- 21882200
TI  - Gastric cancer: biology and clinical manifestations in Israel.
AB  - BACKGROUND: Gastric cancer (GC) in Israel remains incompletely characterized. The
      aim of this study was to define the clinical and pathological characteristics of
      GC in Israel and to compare them to the general Western population. PATIENTS AND
      METHODS: This is a retrospective analysis of 461 consecutive GC patients treated
      at a single institution between 1995 and 2007. Epidemiological and clinical
      pathological data were retrieved from the patients' medical files and the
      institutional electronic database and analyzed using standard statistical
      methods. RESULTS: Epidemiology, clinical manifestations, histopathological
      findings, clinical course, and prognostic factors for disease outcome were all
      similar to those reported in the Western literature. Findings unique to the
      Israeli population included: (1) rarity of GC-associated risk factors; (2)
      increased GC incidence in Ashkenazi Jews; (3) high incidence of second primary
      malignancy and family history of cancer; and (4) no dominancy of proximal GCs.
      CONCLUSION: There do not appear to be any major differences in the biology or
      clinical manifestations of GC in Israel. Western recommendations for diagnosis
      and treatment of GC may therefore be applied to the Israeli patient population.

PMID- 21882201
TI  - Clinicopathologic variables predicting tumor response to neoadjuvant chemotherapy
      in patients with locally advanced gastric cancer.
AB  - BACKGROUND AND OBJECTIVES: To identify clinicopathologic variables that could
      predict pathologic tumor response to neoadjuvant chemotherapy for patients with
      locally advanced gastric cancer. METHODS: The study enrolled 108 patients who
      underwent neoadjuvant chemotherapy followed by surgery between July 2004 and
      December 2010. Tumor responses to neoadjuvant chemotherapy were assessed in terms
      of tumor regression. Statistical analyses were performed to identify factors
      associated with pathologic tumor response. RESULTS: Tumor regression was found in
      22.2% (24/108) patients, patients with tumor regression observed better overall
      survival as compared to that of patients without tumor regression. Univariate and
      multivariate analyses observed that both tumor differentiation and tumor size
      were independent predictors of tumor regression. CONCLUSIONS: This study suggests
      that both tumor differentiation and tumor size is the most important clinical
      predicator of pathologic tumor response, it may be of benefit in the selection of
      treatment options in locally advanced gastric cancer.

PMID- 21882202
TI  - Clinical significance of pathologic subtype in curatively resected ampulla of
      vater cancer.
AB  - BACKGROUND: Ampullary cancer is considered to have a better prognosis than
      cancers of the distal bile duct and pancreas, and recent publications emphasize
      the prognostic importance of the histologic differentiation of the intestinal and
      pancreatobiliary types of ampullary cancer. The aims of this study were to
      identify those factors that affect recurrence after curative resection and to
      investigate differences between the clinicopathologic features of these two
      pathologic subtypes. PATIENTS AND METHODS: The medical records of patients that
      underwent pancreatoduodenectomy for ampullary carcinoma from February 1995 to
      March 2009 at our institute were retrospectively reviewed. One hundred and four
      patients that underwent curative resection for ampullary carcinoma were enrolled
      in this study. One pathologist reviewed all pathologic reports and
      histopathologic findings. Data on clinicopathologic factors and disease free and
      overall survival were analyzed. RESULTS: The 3- and 5-year disease free survival
      rates of the 104 study subjects were 62.2% and 57.7%, respectively, and overall
      survival rates were 69.4% and 60.1%, respectively. Multivariate analysis showed
      that an advanced T stage (P = 0.049), the presence of lymph node metastasis (P =
      0.003), poor differentiation (P = 0.039), and the pancreatobiliary type (P =
      0.022) significantly increased the risk of recurrence. Furthermore, the
      pancreatobiliary type was found to be more associated with an advanced T stage (P
      = 0.009), regional lymph node metastasis (P = 0.007), and perineural invasion (P
      = 0.026) than the intestinal type. In addition, pathologic subtype analysis
      showed that Carcinoembryonic antigen (CEA) level and lymph node metastasis were
      important predictors of recurrence in patients with the intestinal (P = 0.013)
      and pancreatobiliary types, respectively (P = 0.003). CONCLUSIONS: An advanced T
      stage, nodal metastasis, poor differentiation, and the pancreaticobiliary type
      were found to be independent predictors of recurrence after curative resection of
      ampullary carcinoma by multivariate analysis. In addition, the pancreatobiliary
      type tended to present in a more advanced T stage and more frequently with
      regional lymph node involvement and perineural invasion than the intestinal type.
      Furthermore, CEA level and lymph node metastasis were found to be independent
      predictors of recurrence for the intestinal and pancreatobiliary types,
      respectively.

PMID- 21882203
TI  - Swallowing function after transoral laser microsurgery (TLM) +/- adjuvant therapy
      for advanced-stage oropharyngeal cancer.
AB  - OBJECTIVES/HYPOTHESIS: To perform a longitudinal description of swallowing
      function following transoral laser microsurgery (TLM) +/- adjuvant therapy for
      advanced-stage oropharyngeal cancer (OPC) and identify prognostic factors
      associated with swallowing performance. STUDY DESIGN: Retrospective analysis and
      longitudinal descriptive study of swallowing outcomes. METHODS: Patients treated
      with TLM for AJCC stage III-IV OPC at Washington University from 1996 to 2008
      were included. A search of medical records and direct patient contact were
      performed to obtain swallowing function at multiple time points. Persistently
      poor swallowing at 2 year after surgery was the primary outcome measure. Two year
      swallowing outcomes stratified by tumor site and T stage are presented. RESULTS:
      One hundred eighteen patients met criteria for the study (median follow-up 53.9
      months). There were 44 T1's, 41 T2's, 23 T3's and 10 T4's. Forty seven percent
      received radiotherapy and 41% received chemoradiotherapy. Ninety-eight percent
      underwent neck dissection. Patients tolerated TLM well with 82% enjoying good
      swallowing at 1 month after surgery. During adjuvant therapy, at 3 months, good
      swallowing dropped to 55%. At 1 and 2 years after TLM, 89% and 88% of patients
      had good swallowing function, respectively. At 2 years, 9 patients had
      persistently poor swallowing function. 93% of patients with T1 through T3 enjoyed
      good swallowing at 2 years. T4 base of tongue disease was associated with
      persistently poor swallowing function in multivariate analyses (P = 0.0023), with
      40% having good swallowing at 2 years. Preexisting comorbidities and conversion
      to an open procedure were associated with delayed return of swallowing function,
      but not with persistently poor swallowing. Seven patients developed late-onset
      swallowing dysfunction. CONCLUSIONS: Treatment of advanced stage OPC with TLM +/-
      adjuvant therapy results in excellent swallowing outcomes for patients with
      either T1 to T3 tonsil or T1 to T3 base of tongue resections. A detailed,
      longitudinal swallowing profile is presented to assist in preoperative
      counseling.

PMID- 21882204
TI  - The role of TNF-alpha in inflammatory olfactory loss.
AB  - BACKGROUND: Despite the significant health impact of olfactory loss in chronic
      rhinosinusitis (CRS), the underlying pathophysiology is incompletely understood.
      A transgenic mouse model of olfactory inflammation induced by tumor necrosis
      factor-alpha (TNF-alpha) has provided new insights into the cellular and
      molecular basis of inflammatory olfactory loss. Here, we utilize systemic
      corticosteroids to suppress downstream cytokine expression, in order to study the
      direct role of TNF-alpha in CRS-associated olfactory dysfunction. METHODS:
      Transgenic mice were induced to express TNF-alpha in the olfactory epithelium for
      6 weeks. In a subset of mice, 1 mg/kg prednisolone was administered concurrently
      to inhibit downstream inflammatory responses. The olfactory epithelium (OE) was
      analyzed by histology and electro-olfactogram (EOG) recordings. RESULTS:
      Treatment with prednisolone successfully prevented inflammatory infiltration over
      significant regions of the OE. In areas where significant subepithelial
      inflammation was present, a corresponding loss of olfactory neurons was observed.
      In contrast, areas without major inflammatory changes had normal olfactory neuron
      layers, despite chronic local expression of TNF-alpha. Prednisolone partially
      reversed the complete loss of olfaction in the mouse model, preserving odorant
      responses that were significantly diminished compared to controls, but not
      absent. CONCLUSIONS: The addition of prednisolone to the transgenic model of
      olfactory inflammation isolates the direct effects of induced TNF-alpha
      expression on the OE. The finding that prednisolone treatment prevents neuronal
      loss in some regions of the OE suggests that TNF-alpha does not directly cause
      neuronal apoptosis--rather, that subepithelial inflammation or other downstream
      mediators may be responsible. At the same time, EOG results imply that TNF-alpha
      directly causes physiologic dysfunction of olfactory neurons, independent of the
      inflammatory state. An understanding of the role of TNF-alpha and other
      inflammatory cytokines may suggest novel therapeutic strategies for CRS
      associated olfactory loss.

PMID- 21882205
TI  - Prenatal sonographic features of dyssegmental dysplasia Rolland-Desbuquois type.
AB  - Dyssegmental dysplasia is a rare, lethal, autosomal-recessive disorder
      characterized by severe camptomicromelia and anisospondyly. We describe the
      prenatal sonographic findings in an index case of the Rolland-Desbuquois type,
      with the diagnosis made by neonatal skeletal survey. Recognition of the unique
      vertebral disorganization may be used to prenatally distinguish dyssegmental
      dysplasia from other severe short-limbed conditions.

PMID- 21882206
TI  - Engineered nanostructural materials for application in cancer biology and
      medicine.
AB  - Nanotechnology covers a wide variety of fields of research, including chemistry,
      physics, biology and medicine, with extensive applications in cancer, ranging
      from accurate, early detection of malignant lesions to minimizing metastasis.
      Continued development of cancer-targeted therapy has promising advantages:
      maximizing the effectiveness of anticancer drugs while decreasing the harmful
      systemic effects; tumor destruction via heating that takes advantage of magnetic
      nanoparticles' size, magnetization and biocompatibility; novel drug-delivery
      systems; and gene therapy functions to facilitate controlled drug loading and
      release inside the cytoplasm. These and other nanotechnology applications can
      contribute essential new knowledge in the fight against cancer.

PMID- 21882207
TI  - Simultaneous determination of cypermethrin and fenvalerate residues in tomato by
      gas chromatography and their applications to kinetic studies after field
      treatment.
AB  - In this study simultaneous determination of cypermethrin and fenvalerate residues
      in tomato fruit (Lycopesicon esculentum) grown in Khartoum, Sudan, was carried
      out using gas chromatography with electron capture detector (GC-ECD). The method
      was linear in the ranges of 0.075-0.009 and 0.75-0.037 mg/mL for cypermethrin and
      fenvalerate, respectively. The limits of detection and quantification were found
      to be 0.003 and 0.01 mg/mL and 0.014, 0. 047 mg/mL for cypermethrin and
      fenvalerate, respectively. The recoveries of cypermethrin and fenvalerate spiked
      in tomato were 97 +/- 7.5 and 99.5 +/- 1.8%, respectively. The kinetic study of
      the degradation of both pesticides was performed and the ultimate evaluation of
      the kinetic data revealed a first-order kinetics with respect to the tomato
      fruit; an explanation was put forward to account for the results.

PMID- 21882208
TI  - Identification and quantification of free radical scavengers in the flower buds
      of Lonicera species by online HPLC-DPPH assay coupled with electrospray
      ionization quadrupole time-of-flight tandem mass spectrometry.
AB  - Flos Lonicerae, derived from the flower buds of several medicinal Lonicera
      species, is a commonly used herbal medicine with multiple pharmacological
      activities, one of the major ones being antioxidant activity. In this study, free
      radical scavengers in the flower buds of six Lonicera species were screened,
      identified and quantified by online HPLC-DPPH (1,1-diphenyl-2-picrylhydrazyl)
      assay coupled with LC quadrupole time-of-flight tandem mass spectrometry (Q-TOF
      MS/MS). The antioxidants were firstly screened from the complex plant matrix by
      the online HPLC-DPPH assay. Then the active compounds were identified by LC Q-TOF
      MS/MS, and the possible fragmentation pathways were proposed. The reactivity of
      antioxidants available was investigated using an internal standard method by
      online LC assay. The contents of 12 antioxidants were also determined or
      estimated by HPLC coupled with diode array detector. The total antioxidant
      capability determined by the online method was used as the marker to evaluate the
      quality of Flos Lonicerae. The results were important to clarify the material
      basis and therapeutic mechanism of Flos Lonicerae.

PMID- 21882209
TI  - Development of a sensitive liquid chromatography/tandem mass spectrometry method
      for the determination of fenofibric acid in rat plasma.
AB  - A rapid and sensitive LC-MS/MS method for the quantification of fenofibric acid
      in rat plasma was developed and validated. Plasma samples were prepared by liquid
      liquid extraction with a mixture of N-hexane-dichloromethane-isopropanol
      (100:50:5, v/v/v). Isocratic chromatographic separation was performed on a
      reversed-phase Discovery C(18) column (2.1 * 50 mm, 5 um). The mobile phase was
      methanol-water-formic (75:25:0.25, v/v/v). Detection of fenofibric acid and the
      internal standard (IS) diclofenac acid was achieved by ESI MS/MS in the negative
      ion mode using m/z 317 -> m/z 213 and m/z 294 -> m/z 250 transitions,
      respectively. The method was linear from 0.005 to 1.250 ug/mL when 100 MUL plasma
      was analyzed. The lower limit of quantification was 0.005 ug/mL. The intra- and
      inter-day precision values were below 8.2%, and accuracy ranged from -0.9 to 2.1%
      in all quality control samples. The recovery was 90.3-94.7% and 83.3% for
      fenofibric acid and IS, respectively. Total run time for each sample analysis was
      2.5 min. The validated method was successfully applied to a pharmacokinetic study
      in six rats after oral administration of fenofibrate, the ester prodrug of
      fenofibric acid (equivalent to fenofibric acid 5 mg/kg). The method permits
      laboratory scientists with access to the appropriate instrumentation to perform
      rapid fenofibric acid determination.

PMID- 21882210
TI  - Quantification of leonurine, a novel potential cardiovascular agent, in rat
      plasma by liquid chromatography-tandem mass spectrometry and its application to
      pharmacokinetic study in rats.
AB  - Leonurine (SCM-198), an alkaloid from Herba Leonuri, has been suggested as a
      novel cardiovascular agent by pharmacology studies in preclinical stage. In
      present study, we report a simple, rapid and sensitive high-performance liquid
      chromatography-tandem mass spectrometry method (HPLC-MS/MS) for determination of
      leonurine in rat plasma. Leonurine and its internal standard (IS) n-benzoyl-l
      arginine ethyl ester (BAEE) were extracted from plasma samples by one-step
      protein precipitation with perchloric acid. Chromatographic separation was
      performed on an Agilent Zorbax SB-C18 column (150 * 2.1 mm, 5 um) using an
      isocratic elution with acetonitrile-ammonium acetate buffer (10 mm, pH 4.0;
      25:75, v/v) as mobile phase at a flow rate of 0.2 mL/min. Analytes were detected
      by tandem mass spectrometry in positive electrospray ionization (ESI) mode using
      multiple reaction monitoring (MRM) with the transitions of m/z 312.3 -> 181.1 for
      leonurine and m/z 307.2 -> 104.6 for IS. The calibration curves were linear over
      the range of 4-256 ng/mL with a lower limit of quantitation (LLOQ) of 4 ng/mL.
      The intra- and inter-day assay precision (as relative standard deviation) were
      <15%, except which at LLOQ were <20%, with accuracy in the range 98.73-105.42%.
      The validated HPLC-MS/MS method was successfully applied to the pharmacokinetic
      study in rats following oral administration of leonurine.

PMID- 21882211
TI  - Increased expression of putative cancer stem cell markers in primary prostate
      cancer is associated with progression of bone metastases.
AB  - BACKGROUND: A number of putative stem cell markers have been associated with
      aggressiveness of prostate cancer, including alpha 2 and alpha 6 integrin and c
      met. The study aimed to test the hypothesis that the development of bone
      metastasis correlates with the proportion of prostate cancer stem cell-like cells
      present in the primary tumor. METHODS: Prostate tissue samples were obtained from
      patients with high-risk prostatic adenocarcinoma. Prostate cancer tumor tissue
      samples underwent immunohistochemical staining for alpha 2 and alpha 6 integrin
      and c-met; positive and negative controls were included. Samples were scored as
      positive if >5% of cells within the sample stained positively. Survival and bone
      metastasis-free survival curves on the patient cohort were estimated by the
      actuarial method of Kaplan-Meier. RESULTS: A total of 62 patients were included
      in the study. Bone metastases progression rate was 46% at 105 months with a
      median time of 46 months (95% CI: 1-62.5 months); prostate cancer-specific
      survival was 33% at 122 months with a median survival time of 69.4 months (95%
      CI: 63.5-109.4 months). Survival curves show that c-met-, alpha 2, and alpha 6
      integrin-positive tumors were positively associated with the occurrence of bone
      metastasis-free survival. There was a higher level of significance when at least
      c-met and either alpha 2 or alpha 6 integrin was positive. CONCLUSION: It can be
      concluded that percentage of stem cell-like prostate cancer cells has a
      prognostic impact especially on the risk of metastatic bone progression.

PMID- 21882212
TI  - Refining the orthotopic dog prostate cancer (DPC)-1 model to better bridge the
      gap between rodents and men.
AB  - BACKGROUND: Rodent models are often suboptimal for translational research on
      human prostate cancer (PCa). To better fill the gap with human, we refined the
      previously described orthotopic dog prostate cancer (DPC)-1 model. METHODS:
      Cyclosporine (Cy) A was used for immune suppression at varying doses and time
      periods prior and after orthotopic DPC-1 cell implantation in the dog prostate (n
      = 12). Follow up included digital rectal examination, ultrasound prostate imaging
      and biopsies of hypoechoic areas. At necropsy, the prostate, iliosacral lymph
      nodes (LN), lung nodules, and suspicious bone segments were collected for
      histopathology. RESULTS: 15 mg CyA/kg daily for 10 days was optimal for tumor
      take. Maintaining these conditions post-implantation resulted in a rapid tumor
      development within and beyond the prostate and in iliosacral LNs. To minimize
      tumor burden, 10 times less DPC-1 cells were implanted. A series of dogs was next
      followed for 3-4 months, under continuous immune suppression (n = 3) or with CyA
      interruption at 8.5 weeks (n = 2). In all instances, multifocal tumors were found
      within the prostate. Predominant patterns were micropapillary and cribriform.
      Metastases were present in iliosacral LNs and lungs. Moreover, pelvic bone
      metastases producing a mixed osteoblastic/osteolytic reaction were confirmed in
      two dogs, one per group. Lastly, the release of CyA 1-2 weeks post-implantation
      (n = 3) did not prevent tumor growth and spreading to LNs. CONCLUSIONS: The
      continuing growth of DPC-1 tumors despite the release of CyA and, for the first
      time, spreading to bones renders this refined model closer to the spontaneous
      canine and hormone-refractory phase of human PCa.

PMID- 21882213
TI  - Comment on "Finasteride upregulates expression of androgen receptor in
      hyperplastic prostate and LNCaP cells: implications for chemoprevention of
      prostate cancer" by Hsieh et al.

PMID- 21882214
TI  - Tumor focality is not associated with biochemical outcome after radical
      prostatectomy.
AB  - BACKGROUND: The clinical and prognostic significance of unifocal prostatic
      carcinoma is not clearly understood. In the current study, we sought to
      characterize the clinical and pathologic characteristics of unifocal and
      multifocal prostate cancers and to investigate the effects of tumor focality on
      biochemical outcome after radical prostatectomy. METHODS: Our analysis included
      1,444 radical prostatectomy patients with available information concerning the
      number and location of tumor foci in the specimen. Each patient was assigned to
      one of three groups depending on whether they had unifocal, multifocal, or
      extensive cancer. Clinical and pathological features as well as biochemical
      outcomes were compared between the groups. RESULTS: Two hundred and seventy-two
      mens in the study cohort (18.8%) had unifocal cancer. The rates of unifocal
      cancer did not differ significantly between the three studied time intervals
      (17.3% in 1992-1998, 20.5% in 1999-2004, and 17.8% in 2005-2011). The number of
      positive biopsy cores was slightly lower in the unifocal group, while the overall
      amount of biopsy tissue containing cancer was similar in both groups. The
      patients in the multifocal group had higher pathologic Gleason scores, increased
      incidence of positive surgical margin, and larger tumors. The rate of clinically
      significant Gleason score upgrade was significantly higher in the multifocal
      group compared to the unifocal group (35.7% vs. 21.7%, respectively, P < 0.001).
      The biochemical outcome after radical prostatectomy did not differ between
      patients with unifocal and multifocal cancers both on univariate and multivariate
      analyses. CONCLUSIONS: Tumor focality is not an independent prognostic factor of
      biochemical outcome in radical prostatectomy patients.

PMID- 21882215
TI  - Agricultural injury among rural California public high school students.
AB  - OBJECTIVES: The University of California, Davis Youth Agricultural Injury Study
      characterized the farm work and agricultural injury experience among rural
      California Central Valley public high school students enrolled in an agricultural
      sciences curriculum. METHODS: We conducted a cross-sectional survey of
      agricultural injury among students from 10 California Central Valley high schools
      during the 2001-2005 school years. RESULTS: Of 1,783 subjects, 946 (53.1%)
      reported farm work in the previous year, including 97 (10.3%) reporting at least
      one farm work-related injury in the preceding year. After adjustment for sex,
      ethnicity, and hours spent in farm work, injury risk was associated with large
      animal operations (OR 4.15; 95%CI: 1.18, 14.65), feeding large animals (OR 2.38;
      95%CI: 1.15, 4.96), mixing chemicals (OR 1.86; 95%CI: 1.15, 3.03), welding (OR
      2.09; 95%CI: 1.17, 3.72), non-use of seatbelts, and frequent riding in the back
      of an uncovered pick-up truck. Risky attitudes toward farm safety were
      significantly associated with injury. Girls were more likely to suffer an animal
      related injury and boys to suffer injury related to motor vehicles, machinery, or
      tool use. CONCLUSIONS: Adolescents are at similar risk to adults for agricultural
      injury. Although limitations on hazardous tasks and time spent on farm work are
      likely to be the most efficacious means for reducing injury, education will play
      an important role. Educational measures should include inculcating healthy safety
      related attitudes and focus on hazardous tasks, such as those involving animals
      (for girls) and motor vehicles and machinery (for boys).

PMID- 21882216
TI  - Exposure to tobacco smoke and prevalence of symptoms decreased among Finnish
      restaurant workers after the smoke-free law.
AB  - INTRODUCTION: The impact of tobacco legislation and exposure to environmental
      tobacco smoke (ETS) in bars and restaurants were assessed in a national survey.
      METHODS: Questionnaire surveys among restaurant workers were conducted in 2007
      before the smoking ban, and in 2009. RESULTS: The exposure to ETS decreased
      significantly after the launch of the 2007 smoke-free law. During 2007-2009, the
      prevalence of those restaurant workers with no exposure increased from 54% to 82%
      (P-value < 0.0001), and among bartenders from 10% to 70% (P < 0.0001). Employees
      exposed daily for more than 4 hr decreased from 24% to 4% (P < 0.0001) and from
      67% to 9% among bartenders (P < 0.0001). The prevalence of respiratory symptoms
      decreased from 18% to 4% (P < 0.0001) and of eye symptoms from 23% to 6% (P <
      0.0001). CONCLUSION: The reform of tobacco legislation in 2007, which prohibited
      smoking in restaurants and bars, significantly decreased the exposure to ETS and
      the prevalence of symptoms among restaurant workers.

PMID- 21882217
TI  - A case-control study of asphalt and tar exposure and lung cancer in minorities.
AB  - OBJECTIVES: Considerable controversy surrounds the carcinogenic potential of
      asphalt and tar. Since minority individuals may have had relatively high
      historical exposures, we investigated asphalt and tar exposure and lung cancer
      risk among African Americans and Latino Americans. METHODS: We conducted a case
      control study of lung cancer among African Americans and Latino Americans in the
      San Francisco Bay area (422 cases, 894 controls). A questionnaire was used to
      obtain detailed work histories and exposure information. Self-reported exposure
      to asphalt and tar as well as other factors (e.g., smoking, automobile exhaust,
      and asbestos) were evaluated as predictors of lung cancer risk. Potential effect
      modification by cytochrome P450 (CYP) 1A1 was also explored. RESULTS: Self
      reported duration of exposure to asphalt and tar was associated with a
      statistically significant excess risk of lung cancer in the overall population
      (OR: 1.11, 95% CI: 1.01-1.22), evaluating risk per year of exposure. Years of
      exposure to automobile exhaust (OR: 1.02, 95% CI: 1.00-1.05) and asbestos (OR:
      1.04, 95% CI: 1.02-1.06) were also associated with statistically significant
      elevations in risk. In Latino Americans, the lung cancer risks associated with
      polycyclic aromatic hydrocarbon-related exposures were consistently higher in the
      CYP1A1 wild-type subjects as compared to the variant genotype subjects, and the
      interaction was statistically significant for smoking and the CYP1A1 M2
      polymorphism (P-value(interaction) = 0.02). CONCLUSIONS: These data are
      consistent with the literature suggesting that exposure to asphalt and tar may
      increase risk of lung cancer. However, it was not possible to separate the
      effects and asphalt and tar in this study.

PMID- 21882219
TI  - A Monte Carlo investigation of factors influencing latent class analysis: an
      application to eating disorder research.
AB  - OBJECTIVE: Latent class analysis (LCA) has frequently been used to identify
      qualitatively distinct phenotypes of disordered eating. However, little
      consideration has been given to methodological factors that may influence the
      accuracy of these results. METHOD: Monte Carlo simulations were used to evaluate
      methodological factors that may influence the accuracy of LCA under scenarios
      similar to those seen in previous eating disorder research. RESULTS: Under these
      scenarios, the aBIC provided the best overall performance as an information
      criterion, requiring sample sizes of 300 in both balanced and unbalanced
      structures to achieve accuracy proportions of at least 80%. The BIC and cAIC
      required larger samples to achieve comparable performance, while the AIC
      performed poorly universally in comparison. Accuracy generally was lower with
      unbalanced classes, fewer indicators, greater or nonrandom missing data,
      conditional independence assumption violations, and lower base rates of indicator
      endorsement. DISCUSSION: These results provide critical information for
      interpreting previous LCA research and designing future classification studies.

PMID- 21882218
TI  - Effects of reducing the frequency and duration criteria for binge eating on
      lifetime prevalence of bulimia nervosa and binge eating disorder: implications
      for DSM-5.
AB  - OBJECTIVE: We assessed the impact of reducing the binge eating frequency and
      duration thresholds on the diagnostic criteria for bulimia nervosa (BN) and binge
      eating disorder (BED). METHOD: We estimated the lifetime population prevalence of
      BN and BED in 13,295 female twins from the Swedish Twin study of Adults: Genes
      and Environment employing a range of frequency and duration thresholds. External
      validation (risk to cotwin) was used to investigate empirical evidence for an
      optimal binge eating frequency threshold. RESULTS: The lifetime prevalence
      estimates of BN and BED increased linearly as the frequency criterion decreased.
      As the required duration increased, the prevalence of BED decreased slightly.
      Discontinuity in cotwin risk was observed in BN between at least four times per
      month and at least five times per month. This model could not be fit for BED.
      DISCUSSION: The proposed changes to the DSM-5 binge eating frequency and duration
      criteria would allow for better detection of binge eating pathology without
      resulting in a markedly higher lifetime prevalence of BN or BED.

PMID- 21882220
TI  - Bulimia nervosa presenting as rectal purging and rectal prolapse: case report and
      literature review.
AB  - Rectal prolapse, but not rectal purging (excessive finger evacuation to induce
      defecation), has been formally associated with eating disorders in the medical
      literature. We describe a young woman with bulimia nervosa and irritable bowel
      syndrome who used rectal purging as a method of counteracting the effects of her
      binge eating and who underwent two corrective surgeries for rectal prolapse in a
      15-month interval. Further research into the relationship between eating
      disorders, rectal purging, and gastrointestinal dysfunction is called for.

PMID- 21882221
TI  - Forkhead box A1 (FOXA1) is a key mediator of insulin-like growth factor I (IGF-I)
      activity.
AB  - The insulin-like growth factor receptor (IGF-IR) has been implicated in a number
      of human tumors, including breast cancer. Data from human breast tumors has
      demonstrated that IGF-IR is over-expressed and hyper-phosphorylated.
      Additionally, microarray analysis has shown that IGF-I treatment of MCF7 cells
      leads to a gene signature comprised of induced and repressed genes, which
      correlated with luminal B tumors. FOXA1, a forkhead family transcription factor,
      has been shown to be crucial for mammary ductal morphogenesis, similar to IGF-IR,
      and expressed at high levels in luminal subtype B breast tumors. Here, we
      investigated the relationship between FOXA1 and IGF-I action in breast cancer
      cells. We show that genes regulated by IGF-I are enriched for FOXA1 binding
      sites, and knock down of FOXA1 blocked the ability of IGF-I to regulate gene
      expression. IGF-I treatment of MCF7 cells increased the half-life of FOXA1
      protein and this increase in half-life appeared to be dependent on canonical IGF
      I signal transduction through both MAPK and AKT pathways. Finally, knock down of
      FOXA1 led to a decreased ability of IGF-I to induce proliferation and protect
      against apoptosis. Together, these results demonstrate that IGF-I can increase
      the stability of FOXA1 protein expression and place it as a critical mediator of
      IGF-I regulation of gene expression and IGF-I-mediated biological responses.

PMID- 21882222
TI  - Decreased bone mineral density and reduced bone quality in H(+) /K(+) ATPase beta
      subunit deficient mice.
AB  - Proton pump inhibitors (PPIs) are widely used against gastroesophageal reflux
      disease. Recent epidemiological studies suggest that PPI users have an increased
      risk of fractures, but a causal relationship has been questioned. We have
      therefore investigated the skeletal phenotype in H(+) /K(+) ATPase beta-subunit
      knockout (KO) female mice. Skeletal parameters were determined in 6- and 20-month
      old KO mice and in wild-type controls (WT). Whole body bone mineral density (BMD)
      and bone mineral content (BMC) were measured by dual energy X-ray absorptiometry
      (DXA). Femurs were examined with uCT analyses and break force were examined by a
      three-point bending test. Plasma levels of gastrin, RANKL, OPG, osteocalcin,
      leptin, and PTH were analyzed. KO mice had lower whole body BMC at 6 months (0.53
      vs. 0.59 g, P = 0.035) and at 20 months (0.49 vs. 0.74 g, P < 0.01) compared to
      WT as well as lower BMD at 6 months (0.068 vs. 0.072 g/cm(2) , P = 0.026) and 20
      months (0.067 vs. 0.077 g/cm(2) , P < 0.01). Mechanical strength was lower in KO
      mice at the age of 20 months (6.7 vs. 17.9 N, P < 0.01). Cortical thickness at 20
      months and trabecular bone volume% at 6 months were significantly reduced in KO
      mice. Plasma OPG/RANKL ratio and PTH was increased in KO mice compared to
      controls. H(+) /K(+) ATPase beta subunit KO mice had decreased BMC and BMD,
      reduced cortical thickness and inferior mechanical bone strength. Whereas the
      mechanism is uncertain, these findings suggest a causal relationship between long
      term PPI use and an increased risk of fractures.

PMID- 21882223
TI  - Facilitation of human osteoblast apoptosis by sulindac and indomethacin under
      hypoxic injury.
AB  - Hypoxic-ischemia injury occurs after trauma causes consequential bone necrosis.
      Non-steroid anti-inflammatory drugs (NSAIDs) are frequently used in orthopedic
      clinics for pain relief. However, the underlying mechanism and outcome for usage
      of NSAIDs is poorly understood. To investigate the damage and loss of osteoblast
      function in hypoxia, two hypoxia mimetics, cobalt chloride (CoCl(2)) and
      desferrioxamine (DFO), were used to create an in vitro hypoxic microenvironment.
      The cell damage was observed by decreases of cell viability and increases in
      cyclooxygenase-2 and cleaved poly(ADP-ribose) polymerase (PARP). Cell apoptosis
      was confirmed by WST-1 cytotoxic assays and flow cytometry. The functional
      expression of osteoblast in alkaline phosphatase (ALP) activity was significantly
      decreased by CoCl(2) and inhibited when treated with DFO. To simulate the use of
      NSAID after hypoxic injury, four types of anti-inflammatory drugs, sulindac
      sulfide (SUL), indomethacin (IND), aspirin (Asp), and sodium salicylate (NaS),
      were applied to osteoblasts after 1 h of hypoxia mimetic treatment. SUL and IND
      further enhanced cell death after hypoxia. ALP activity was totally abolished in
      hypoxic osteoblasts under IND treatment. Facilitation of osteoblast apoptosis
      occurred regardless of IND dosage under hypoxic conditions. To investigate
      osteoblast in vivo, local hypoxia was created by fracture of tibia and then
      treated the injured mice with IND by oral feeding. IND-induced osteoblast
      apoptosis was confirmed by positive staining of TUNEL assay in fractured mice.
      Significant delay of fracture healing in bone tissue was also observed with the
      treatment of IND. These results provide information pertaining to choosing
      appropriate anti-inflammatory drugs for orthopedic patients.

PMID- 21882224
TI  - Recovery of DeltaF508-CFTR function by analogs of hyaluronan disaccharide.
AB  - We recently discovered that hyaluronan was exported from fibroblasts by MRP5 and
      from epithelial cells by cystic fibrosis (CF) transmembrane conductance regulator
      (CFTR) that was known as a chloride channel. On this basis we developed membrane
      permeable analogs of hyaluronan disaccharide as new class of compounds to modify
      their efflux. We found substances that activated hyaluronan export from human
      breast cancer cells. The most active compound 2-(2-acetamido-3,5
      dihydroxyphenoxy)-5-aminobenzoic acid (Hylout4) was tested for its influence on
      the activity of epithelial cells. It activated the ion efflux by normal and
      defective DeltaF508-CFTR. It also enhanced the plasma membrane concentration of
      the DeltaF508-CFTR protein and reduced the transepithelial resistance of
      epithelial cells. In human trials of healthy persons, it caused an opening of
      CFTR in the nasal epithelium. Thus compound Hylout4 is a corrector that recovered
      DeltaF508-CFTR from intracellular degradation and activated its export function.

PMID- 21882225
TI  - Interaction between PKR and PACT mediated by LPS-inducible NF-kappaB in human
      gingival cells.
AB  - The double-stranded RNA-dependent protein kinase (PKR) is a serine/threonine
      kinase expressed constitutively in mammalian cells. PKR is activated upon virus
      infection by double-stranded RNA (dsRNA), and plays a critical role in host
      antiviral defense mechanisms. PKR is also known to regulate various biological
      responses, including cell differentiation and apoptosis. However, whether PKR is
      involved in the progress of periodontitis is not clear. The present study
      explained the phosphorylation of PKR by LPS in the human gingival cell line, Sa3.
      Expression of genes encoding LPS receptors was detected in Sa3 cells and
      treatment of cells with 1 ug/mL LPS for 6 h caused PKR phosphorylation. LPS
      elevated the expression of the protein activator of PKR (PACT) mRNA and protein,
      followed by the enhanced association between PACT and PKR within 3 h. In
      addition, LPS treatment induced the translocation of NF-kappaB to the nucleus
      after 30 min, and inhibition of NF-kappaB decreased the PACT-PKR interaction
      induced by LPS. The level of pro-inflammatory cytokine mRNA, including
      interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha), appeared within
      45 min and reached at the maximal levels by 90 min after the addition of LPS.
      This induction of pro-inflammatory cytokines was not affected by RNAi-mediated
      silencing of PKR and a pharmacological inhibitor of PKR, whereas the inhibition
      of NF-kappaB decreased it. These results indicated that LPS induces PKR
      phosphorylation and the PACT-PKR association in Sa3 cells. Our results also
      suggest that NF-kappaB is involved in the PACT-PKR interaction and the production
      of pro-inflammatory cytokines in periodontitis.

PMID- 21882226
TI  - A microRNA "target pools" remains mysterious.

PMID- 21882227
TI  - Experimental hyperprolinemia induces mild oxidative stress, metabolic changes,
      and tissue adaptation in rat liver.
AB  - The present study investigated the effects of chronic hyperprolinemia on
      oxidative and metabolic status in liver and serum of rats. Wistar rats received
      daily subcutaneous injections of proline from their 6th to 28th day of life.
      Twelve hours after the last injection the rats were sacrificed and liver and
      serum were collected. Results showed that hyperprolinemia induced a significant
      reduction in total antioxidant potential and thiobarbituric acid-reactive
      substances. The activities of the antioxidant enzymes catalase and superoxide
      dismutase were significantly increased after chronic proline administration,
      while glutathione (GSH) peroxidase activity, dichlorofluorescin oxidation, GSH,
      sulfhydryl, and carbonyl content remained unaltered. Histological analyses of the
      liver revealed that proline treatment induced changes of the hepatic
      microarchitecture and increased the number of inflammatory cells and the glycogen
      content. Biochemical determination also demonstrated an increase in glycogen
      concentration, as well as a higher synthesis of glycogen in liver of
      hyperprolinemic rats. Regarding to hepatic metabolism, it was observed an
      increase on glucose oxidation and a decrease on lipid synthesis from glucose.
      However, hepatic lipid content and serum glucose levels were not changed. Proline
      administration did not alter the aminotransferases activities and serum markers
      of hepatic injury. Our findings suggest that hyperprolinemia alters the liver
      homeostasis possibly by induction of a mild degree of oxidative stress and
      metabolic changes. The hepatic alterations caused by proline probably do not
      implicate in substantial hepatic tissue damage, but rather demonstrate a process
      of adaptation of this tissue to oxidative stress. However, the biological
      significance of these findings requires additional investigation.

PMID- 21882228
TI  - Identification and characterization of a bactericidal and proapoptotic peptide
      from Cycas revoluta seeds with DNA binding properties.
AB  - Nowadays, novel pharmacies have been screened from plants. Among them are the
      peptides, which show multiple biotechnological activities. In this report, a
      small peptide (Ala-Trp-Lys-Leu-Phe-Asp-Asp-Gly-Val) with a molecular mass of
      1,050 Da was purified from Cycas revoluta seeds by using reversed-phase liquid
      chromatography. This peptide shows clear deleterious effects against human
      epidermoid cancer (Hep2) and colon carcinoma cells (HCT15). It caused inhibition
      of cancer cell proliferation and further disruption of nucleosome structures,
      inducing apoptosis by direct DNA binding. A remarkable antibacterial activity was
      also observed in this same peptide. Nevertheless, no significant lysis of normal
      RBC cells was observed in the presence of peptide. Additionally, an acetylation
      at the N-termini portion is able to reduce both activities. Bioinformatics tools
      were also utilized for construction of a three-dimensional model showing a single
      amphipathic helix. Since in vitro binding studies show that the target of this
      peptide seems to be DNA, theoretical docking studies were also performed to
      better understand the interaction between peptide and nucleic acids and also to
      shed some light on the acetyl group role. Firstly, binding studies showed that
      affinity contacts basically occur due to electrostatic attraction. The complex
      peptide-ssDNA was clearly oriented by residues Ala(1), Lys(3), and Asp(6), which
      form several hydrogen bonds that are able to stabilize the complex. When acetyl
      was added, hydrogen bonds are broken, reducing the peptide affinity. In summary,
      it seems that information here provided could be used to design a novel
      derivative of this peptide which a clear therapeutic potential.

PMID- 21882229
TI  - Apoptosis- and endoplasmic reticulum stress-related genes were regulated by
      estrogen and progesterone in the uteri of calbindin-D(9k)  and -D(28k)  knockout
      mice.
AB  - Calcium (Ca(2+)) is an important regulator of apoptotic signaling. Calbindin
      D(9k) (CaBP-9k) and -D(28k) (CaBP-28k) have a high affinity for Ca(2+) ions.
      Uterine calbindins appear to be involved in the regulation of myometrial activity
      by intracellular Ca(2+). In addition, uterine calbindins are expressed in the
      mouse endometrium and are regulated by steroid hormones during implantation and
      development. The aim of the present study was to evaluate the regulation of
      apoptosis in the uteri of CaBP-9k, CaBP-28k, and CaBP-9k/28k knockout (KO) mice.
      Our findings indicated that Bax protein was enhanced in the uteri of CaBP-28k and
      CaBP-9k/28k KO mice compared to wild-type (WT) and CaBP-9k KO mice, but no
      difference was observed in Bcl-2 protein expression. The expressions of caspase
      3, 6, and 7 proteins were higher in both CaBP-28k and CaBP-9k/28k KO mice than in
      WT and CaBP-9k KO mice. These results suggest that the absence of CaBP-28k
      increases apoptotic signaling. We also investigated the expression of endoplasmic
      reticulum (ER) stress genes by Western blot analysis in calbindin KO mice. C/EBP
      homologous protein and immunoglobulin heavy chain-binding protein protein levels
      were elevated in CaBP-28k KO mice compared to WT mice. When immature mice were
      treated with 17beta-estradiol (E2) or progesterone (P4) for 3 days, we found that
      the expressions of Bax and caspase 3 protein were increased by E2 treatment in WT
      and CaBP-9k KO mice, and by P4 treatment in CaBP-28k KO mice. These results
      indicate that CaBP-28k blocks the up-regulation of apoptosis-related genes and ER
      stress genes, implying that CaBP-28k may decrease the expression of genes
      involved in apoptosis and ER stress in murine uterine tissue.

PMID- 21882230
TI  - The feasibility of using mosquitofish (Gambusia affinis) for detecting endocrine
      disrupting chemicals in the freshwater environment.
AB  - We evaluated the utility of gene-transcriptional responses in the liver of
      mosquitofish (Gambusia affinis), a species introduced to many countries and
      therefore widely available, for detecting endocrine-disrupting activity in water.
      Exposure to beta-naphthoflavone, an aryl hydrocarbon receptor (AhR) agonist,
      significantly increased the transcript of the cytochrome P4501A gene (cyp1a),
      peaking at 24 h, in both sexes at concentrations of 10 ug/L or more. 17beta
      Estradiol (E(2) ) at 500 ng/L increased the number of males showing gene
      transcription of precursors of yolk protein, vitellogenin (Vtga, Vtgb, and Vtgc),
      at 24, 48, and 72 h. Exposure for 48 h to bisphenol A (BPA), an estrogen mimic,
      also increased vtg-positive males at 1 mg/L or more. Leachate from a Japanese
      stable-type landfill significantly increased vtg-positive males after 48 h
      exposure, and the in vitro activity of the leachate against the estrogen receptor
      (ER) was estimated as an E(2) equivalent of 240 ng/L by yeast transfected with
      the ER. Chemical analysis showed that major contributors to the ER activation
      were BPA and 4-tert-octylphenol. This leachate and drainage water from a control
      type landfill had AhR activities, estimated by yeast with the AhR, but had no
      significant effect on cyp1a transcription. These results showed that mosquitofish
      are suitable for detecting in vivo AhR and ER effects, but are insensitive to
      E(2).

PMID- 21882231
TI  - Polybrominated diphenyl ethers in surface soils from e-waste recycling areas and
      industrial areas in South China: concentration levels, congener profile, and
      inventory.
AB  - Polybrominated diphenyl ethers (PBDEs) were determined in 60 surface soils from
      two e-waste recycling sites (Qingyuan and Guiyu, China) and their surrounding
      areas to assess the extent and influence of PBDEs from e-waste recycling sites on
      the surrounding areas. A total of 32 surface soils from industrial areas in South
      China were also investigated for comparison. The mean concentrations of total
      PBDEs in the e-waste recycling sites of Guiyu and Qingyuan were 2,909 and 3,230
      ng/g dry weight, respectively, whereas the PBDE concentrations decreased
      dramatically (1-2 orders of magnitude) with increasing distance from the
      recycling site, suggesting that the e-waste recycling activities were the major
      source of PBDEs in the surrounding areas. Decabromodiphenyl ethers accounted for
      77.0 to 85.8% of total PBDEs in e-waste recycling areas, whereas it accounted for
      90.2% in industrial areas. Principal component analysis showed that the major
      source of PBDEs in e-waste recycling areas were a combination of penta-, octa-,
      and deca-BDE commercial formulations, whereas deca-BDE commercial formulations
      were the major source of PBDE congeners in industrial areas. The inventories of
      PBDEs gave preliminary estimates of 6.22 tons and 13.4 tons for the e-waste
      recycling areas and industrial areas. The results suggested that significantly
      higher PBDEs in the e-waste recycling sites have already affected surrounding
      areas negatively within a relatively large distance. Because of the environmental
      persistence, bioaccumulation, and toxicity of PBDEs, improving the recycling
      techniques employed at such facilities and developing e-waste management policies
      are necessary.

PMID- 21882232
TI  - Therapeutic apheresis instrumentation.
AB  - This article provides a concise overview of therapeutic apheresis medicine
      instrumentation. Three instrument modalities are discussed: (1) centrifugation
      based instruments, (2) extracorporeal photopheresis instruments (a subset of
      centrifugation-based instruments), and (3) column-based instruments.

PMID- 21882233
TI  - Conventional apheresis therapies: a review.
AB  - This article reviews advances in the scientific basis and medical practice of
      plasmapheresis and cytapheresis therapies. Newly-characterized autoantibodies in
      neuromyelitis optica, Guillain-Barre variants, anti-neutrophil cytoplasmic
      antibody (ANCA) vasculitides, etc., exemplify the modern molecular biology which
      now provides a rigorous framework of understanding for the clinical practice of
      plasmapheresis. Clinical trials continue to clarify the appropriate use of
      therapeutic plasmapheresis (TPE) in these and other diseases. Centrifugal (cTPE)
      and membrane filtration (mTPE) types of plasmapheresis are compared, with details
      of the plasmapheresis prescription, anticoagulation choices, replacement fluids
      and other practical considerations. Plasma removal is more efficient with cTPE;
      mTPE systems have a lower plasma extraction ratio, and therefore require higher
      blood flow rates or longer procedure times. Autoantibodies and other pathogenic
      macromolecules targeted for removal by plasmapheresis can be depleted predictably
      when the plasma is discarded, as in conventional TPE. On-line plasma processing
      to regenerate the patient's own plasma avoids the need for replacement albumin
      solutions or plasma transfusion, but is inherently less efficient at removing the
      target molecule, so usually requires a longer procedure. Therapeutic white cell
      reduction (leukapheresis), platelet reduction (thrombocytapheresis) and red cell
      exchange (erythrocytapheresis) require centrifugal apheresis systems.

PMID- 21882234
TI  - Apheresis medicine state of the art in 2010: American Society for Apheresis fifth
      special edition of the Journal of Clinical Apheresis.
AB  - The quality of evidence supporting the use of apheresis in the treatment of
      individual diseases and disorders is often limited. For most diseases and
      disorders, randomized controlled trials of the use of apheresis have not been
      performed and for many, due to rarity of the condition, it is unlikely that they
      will ever be performed. In keeping with its vision, the American Society for
      Apheresis (ASFA) has created and regularly updated guidelines on the use of
      apheresis in the treatment of disease. These guidelines seek to summarize the
      literature on the use of apheresis in treating diseases, provide a critical
      review of this literature, and give practical guidance to apheresis
      practitioners. The most recent ASFA guidelines were published in 2010. This
      article reviews the history of the ASFA guidelines, the changes that were made in
      the 2010 guidelines, and future directions and plans for these guidelines. The
      2010 ASFA guidelines on the use of therapeutic apheresis in clinical practice
      represent the state of the art in apheresis medicine in 2010.

PMID- 21882235
TI  - Introduction to this issue: violent and antisocial behavior in women.

PMID- 21882236
TI  - Effect of cementing technique and cement type on thermal necrosis in hip
      resurfacing arthroplasty--a numerical study.
AB  - Femoral fractures within resurfacing implants have been associated with bone
      necrosis, possibly resulting from heat generated by cement polymerization. The
      amount of heat generated depends on cement mantle volume and type of cement.
      Using finite element analysis, the effect of cement type and volume on thermal
      necrosis was analyzed. Based on CT-data of earlier implantations, two different
      models were created: a thick mantle model, representing a low-viscosity "cement
      filling" technique, and a thin mantle model, representing a high viscosity
      "cement packing" technique. Six cement types were analyzed. The polymerization
      heat generation and its effect on bone necrosis were predicted. In the thin
      cement mantle models, no thermal necrosis was predicted. Thick cement mantle
      models produced thermal necrosis at the cement-bone interface depending on cement
      type. In the worst case, 6% of the bone at the cement-bone interface became
      necrotic, covering almost the entire cross-sectional area. The current findings
      suggest a potential thermal drawback of thick cement mantles, although it is
      unclear whether thermal bone necrosis significantly affects implant fixation or
      increases the fracture risk. Furthermore, our study showed distinct differences
      between the heat generated and resulting thermal damage caused by the various
      cement types.

PMID- 21882237
TI  - Microbiological and pharmacological tests on new antibiotic-loaded PMMA-based
      composites for the treatment of osteomyelitis.
AB  - Local antibiotic diffusion in rabbit femurs from two new PMMA-based and nail
      shaped composites, enriched with beta-tricalcium phosphate (P-TCP) and BaSO(4) or
      only with BaSO(4) (P-BaSO(4) ), and soaked in a solution of gentamicin (G) and
      vancomycin (V) was studied. Nails were implanted into the intramedullary cavity
      of healthy and osteomyelitic femurs to study the resolution of infection and to
      quantify the antibiotic penetration into bone by microbiological,
      pharmacological, and histological tests. A significant progression of
      osteomyelitis was recorded 7 weeks after MRSA inoculation, whereas no bacteria
      were found in animals treated with antibiotic-loaded nails as confirmed by
      microbiology and histology (Smeltzer score). The release of both antibiotics from
      composites was high and prompt both in healthy and infected bone; the amount of V
      was higher than that of G in all bone samples. Antibiotics of both composites
      were still present in bone 3 weeks after nail implantation. The P-BaSO4 composite
      released a lower amount of antibiotics than did P-TCP. The G-V combination in
      vivo exerted a synergistic bactericidal effect, which was confirmed by
      microbiological, histological, and clinical results (no infection). These new
      porous PMMA composites, soaked in G-V solution in the operating room, might be an
      effective and useful drug delivery system for osteomyelitis treatment.

PMID- 21882238
TI  - Mechanically induced calcium signaling in chondrocytes in situ.
AB  - Changes in intracellular calcium (Ca(2+)) concentration, also known as Ca(2+)
      signaling, have been widely studied in articular cartilage chondrocytes to
      investigate pathways of mechanotransduction. Various physical stimuli can
      generate an influx of Ca(2+) into the cell, which in turn is thought to trigger a
      range of metabolic and signaling processes. In contrast to most studies, the
      approach used in this study allows for continuous real time recording of calcium
      signals in chondrocytes in their native environment. Therefore, interactions of
      cells with the extracellular matrix (ECM) are fully accounted for. Calcium
      signaling was quantified for dynamic loading conditions and at different
      temperatures. Peak magnitudes of calcium signals were greater and of shorter
      duration at 37 degrees C than at 21 degrees C. Furthermore, Ca(2+) signals were
      involved in a greater percentage of cells in the dynamic compared to the
      relaxation phases of loading. In contrast to the time-delayed signaling observed
      in isolated chondrocytes seeded in agarose gel, Ca(2+) signaling in situ is
      virtually instantaneous in response to dynamic loading. These differences between
      in situ and in vitro cell signaling responses might provide crucial insight into
      the role of the ECM in providing pathways of mechanotransduction in the intact
      cartilage that are absent in isolated cells seeded in gel constructs.

PMID- 21882239
TI  - Age-related changes in organization and content of the collagen matrix in rabbit
      cortical bone.
AB  - The organization and composition of the collagen matrix of cortical bone changes
      as the bone matures due to growth and mechanical loading. We aimed to investigate
      the composition and organization of the collagen matrix in rabbit cortical bone
      during maturation using Fourier transform infrared (FTIR) microspectroscopy and
      polarized light microscopy (PLM). FTIR and PLM findings were compared to
      biochemical analysis from an earlier study. Mid-diaphyseal samples from left
      femora of female New Zealand White rabbits were used. The animal age ranged from
      newborn to 18-month old (5 age groups, n = 10 per group). The bones had earlier
      been decalcified and evaluated with biochemistry. In this study, collagen
      content, orientation, collagen cross-linking and spatial heterogeneity of all
      parameters was evaluated. Similar results were obtained when collagen content was
      evaluated with FTIR and PLM compared to the collagen content assessed with BA.
      Collagen content, orientation and collagen maturity increased significantly until
      the age of 3 months and remained similar thereafter. Simultaneously, spatial
      heterogeneity of the measured parameters decreased. Based on these findings, it
      seems that the collagen matrix of rabbit bone attains its mature state around 3
      months of age, which is before the overall skeletal maturity is reached.

PMID- 21882240
TI  - Optical requirements on magnification systems for intracranial video
      microsurgery.
AB  - INTRODUCTION: The basic idea of video-microsurgery is the improvement of
      ergonomic conditions in microsurgical procedures by replacing the bulky operating
      microscope with a compact videosystem. OBJECTIVE: To specify optical requirements
      on a videosystem for microsurgical intracranial procedures in neurosurgery.
      METHODS: During 27 microsurgical intracranial procedures (12 cerebellopontine
      angle and 15 supratentorial) zoom factor, focus distance and illumination
      parameters of the operating microscope were continuously recorded. Ergonomic
      aspects were documented as well. RESULTS: The zoom factor ranged from 1.7 to 13.5
      in CPA procedures and from 1.4 to 13.4 in supratentorial procedures. The focus
      distance ranged from 180 mm to 367 mm in CPA procedures and from 188 mm-472 mm in
      supratentorial procedures. CONCLUSION: From an optical point of view current
      operating microscopes meet the requirements of intracranial microneurosurgery.
      However, ergonomically further developments are highly desirable. Video
      microsurgery is a promising field and could hold a solution to this problem.

PMID- 21882241
TI  - No significant association between SIRT1 gene and methamphetamine-induced
      psychosis in the Japanese population.
AB  - OBJECTIVES: We previously showed that the sirtuin 1 gene (SIRT1 gene), one of the
      clock genes, was associated with schizophrenia in a Japanese patient population.
      Because the symptoms of methamphetamine (METH)-induced psychosis are similar to
      those of paranoid type schizophrenia and because not every METH user develops
      psychosis, it is conceivable that METH-induced psychosis and schizophrenia have
      common susceptibility genes. Therefore, we conducted an analysis of the
      association of SIRT1 gene with METH-induced psychosis, hypothesizing a
      significant relationship. METHODS: This paper presents a case-control study of
      the SIRT1 gene in 515 Japanese individuals (197 with METH-induced psychosis and
      318 age-matched and sex-matched controls) with four tagging single nucleotide
      polymorphisms (rs12778366, rs2273773, rs4746720, and rs10997875), selected a
      priori using the HapMap database. RESULTS: rs10997875 (located in the 3' flanking
      region) was associated with METH-induced psychosis (unadjusted p(genotype)  =
      0.0203). However, these results became non-significant after Bonferroni
      correction (corrected p(genotype)  = 0.0812). In the all-marker haplotype
      analysis, the SIRT1 gene was not associated with METH-induced psychosis (p =
      0.146). CONCLUSION: Our findings suggest that SIRT1 gene does not contribute to
      the development of METH-induced psychosis in the Japanese population. However, a
      replication study using larger samples should be conducted to obtain conclusive
      results.

PMID- 21882242
TI  - Engagement in leisure activities and benzodiazepine use in a French community
      dwelling elderly population.
AB  - OBJECTIVE: The prevalence of benzodiazepine use among community-dwelling older
      persons varies between 10% and 30%. The aim of this study was to explore the
      association between leisure activities and the use of benzodiazepine among older
      persons living at home. METHODS: The study population included 4848 persons aged
      65 years and over living in either of two French cities. Information was
      collected from a questionnaire administered to the respondents by trained
      psychologists during face-to-face interviews at home and from a self-administered
      questionnaire. Baseline examination included socio-demographic characteristics,
      drug use and leisure activities. We classified as benzodiazepine users subjects
      who reported use of at least one benzodiazepine during the month preceding the
      interview. The association between the use of benzodiazepine and leisure
      activities was assessed by logistic regression adjusted on known potential
      confounders. RESULTS: More than 18% of participants reported use of at least one
      benzodiazepine. The adjusted odds ratio (OR) of benzodiazepine use associated
      with no or lower participation versus participation in the following activities
      were as follows: OR = 1.31 (95% confidence interval (CI): 1.09 to 1.58) for
      mental activity; OR = 1.50 (CI: 1.12 to 2.03) for physical activity; OR = 1.28
      (CI: 1.05 to 1.55) for productive activity and OR = 0.82 (CI: 0.69 to 0.97) for
      recreational activity. CONCLUSION: Low engagement in stimulating activities and
      high engagement in sedentary activities were associated with recent
      benzodiazepine use.

PMID- 21882243
TI  - Nrf2 deficiency potentiates methamphetamine-induced dopaminergic axonal damage
      and gliosis in the striatum.
AB  - Oxidative stress that correlates with damage to nigrostriatal dopaminergic
      neurons and reactive gliosis in the basal ganglia is a hallmark of
      methamphetamine (METH) toxicity. In this study, we analyzed the protective role
      of the transcription factor Nrf2 (nuclear factor-erythroid 2-related factor 2), a
      master regulator of redox homeostasis, in METH-induced neurotoxicity. We found
      that Nrf2 deficiency exacerbated METH-induced damage to dopamine neurons, shown
      by an increase in loss of tyrosine hydroxylase (TH)- and dopamine transporter
      (DAT)-containing fibers in striatum. Consistent with these effects, Nrf2
      deficiency potentiated glial activation, indicated by increased striatal
      expression of markers for microglia (Mac-1 and Iba-1) and astroglia (GFAP) one
      day after METH administration. At the same time, Nrf2 inactivation dramatically
      potentiated the increase in TNFalpha mRNA and IL-15 protein expression in GFAP+
      cells in the striatum. In sharp contrast to the potentiation of striatal damage,
      Nrf2 deficiency did not affect METH-induced dopaminergic neuron death or
      expression of glial markers or proinflammatory molecules in the substantia nigra.
      This study uncovers a new role for Nrf2 in protection against METH-induced
      inflammatory and oxidative stress and striatal degeneration.

PMID- 21882244
TI  - Reduction in expression of the astrocyte glutamate transporter, GLT1, worsens
      functional and histological outcomes following traumatic spinal cord injury.
AB  - The astrocyte glutamate transporter, GLT1, is responsible for the vast majority
      of glutamate uptake in the adult central nervous system (CNS), thereby regulating
      extracellular glutamate homeostasis and preventing excitotoxicity. Glutamate
      dysregulation plays a central role in outcome following traumatic spinal cord
      injury (SCI). To determine the role of GLT1 in secondary cell loss following SCI,
      mice heterozygous for the GLT1 astrocyte glutamate transporter (GLT1+/-) and wild
      type mice received thoracic crush SCI. Compared with wild-type controls, GLT1+/-
      mice had an attenuated recovery in hindlimb motor function, increased lesion
      size, and decreased tissue sparing. GLT1+/- mice showed a decrease in intraspinal
      GLT1 protein and functional glutamate uptake compared with wild-type mice,
      accompanied by increased apoptosis and neuronal loss following crush injury.
      These results suggest that astrocyte GLT1 plays a role in limiting secondary cell
      death following SCI, and also show that compromise of key astrocyte functions has
      significant effects on outcome following traumatic CNS injury. These findings
      also suggest that increasing intraspinal GLT1 expression may represent a
      therapeutically relevant target for SCI treatment.

PMID- 21882245
TI  - Adolescent exposure to the World Trade Center attacks, PTSD symptomatology, and
      suicidal ideation.
AB  - This study examined the associations between different types of trauma exposure,
      posttraumatic stress disorder (PTSD) symptoms, and suicidal ideation among New
      York City adolescents 1 year after the World Trade Center attacks. A sample of
      817 adolescents, aged 13-18, was drawn from 2 Jewish parochial high schools (97%
      participation rate). We assessed 3 types of trauma exposure, current (within the
      past month) and past (within the past year) suicidal ideation, and current PTSD
      symptoms. Findings indicated that probable PTSD was associated with increased
      risk for suicidal ideation. Exposure to attack-related traumatic events increased
      risk for both suicidal ideation and PTSD. However, specific types of trauma
      exposure differentially predicted suicidal ideation and PTSD: knowing someone who
      was killed increased risk for PTSD, but not for suicidal ideation, and having a
      family member who was hurt but not killed, increased risk for suicidal ideation,
      but not for PTSD. This study extends findings from the adult literature showing
      associations between trauma exposure, PTSD, and increased suicidal ideation in
      adolescents.

PMID- 21882247
TI  - The September 11, 2001 terrorist attacks: ten years after.

PMID- 21882246
TI  - PTSD and alcohol use after the World Trade Center attacks: a longitudinal study.
AB  - Research suggests that posttraumatic stress disorder (PTSD) is associated with
      increased alcohol use, but the findings have not been consistent. We assessed
      alcohol use, binge drinking, and psychotropic medication use longitudinally in
      1,681 New York City adults, representative of the 2000 census, 2 years after the
      World Trade Center attacks. We found that, with the exception of a modified CAGE
      Questionnaire index for alcohol, alcohol use showed a modest increase over time
      and was related to PTSD symptoms, with an increase of about 1 more drink per
      month for those with PTSD, even though overall levels appeared to be within the
      National Institute on Alcohol Abuse and Alcoholism's safe range. Psychotropic
      medication use followed a similar trend; those with PTSD used psychotropics about
      20 more days over the past year than those without. Because the study analyses
      adjusted for key psychosocial variables and confounders, it is not clear if the
      increased alcohol use following trauma exposure is associated with self
      medication of PTSD symptoms, whether increased alcohol use prior to exposure is a
      risk for delayed-onset PTSD, or whether a third unmeasured variable is involved.
      Further research is warranted.

PMID- 21882248
TI  - Predictors of the impact of the September 11th terrorist attacks on victims of
      intimate partner violence.
AB  - This study examined the role of several hypothesized predictors of the impact of
      a potentially traumatic event, the terrorist attacks of September 11, 2001
      (9/11), on a sample of women experiencing intimate partner violence (IPV) and
      related posttraumatic stress symptoms (PTSS). We found that IPV-related PTSS
      mediated the relationship between IPV and 9/11-related PTSS, confirming the
      hypothesis that severity of symptoms related to prior trauma plays a role in the
      development and severity of PTSS related to subsequent potentially traumatic
      events. Media exposure and threat appraisal were significantly positively
      associated with 9/11-related PTSS, whereas social support was significantly
      negatively associated with 9/11-related PTSS, with none of these variables
      serving as moderators of the relationship between IPV-related and 9/11-related
      PTSS. Our results suggest that trauma-related psychiatric history is an important
      factor in the development of PTSS subsequent to an additional potentially
      traumatic event, even after adjusting for relevant variables occurring at the
      time of that event.

PMID- 21882249
TI  - Alterations in affective processing of attack images following September 11,
      2001.
AB  - The events of September 11, 2001 created unprecedented uncertainty about safety
      in the United States and created an aftermath with significant psychological
      impact across the world. This study examined emotional information encoding in 31
      healthy individuals whose stress response symptoms ranged from none to a moderate
      level shortly after the attacks as assessed by the Impact of Event Scale-Revised.
      Participants viewed attack-related, negative (but attack-irrelevant), and neutral
      images while their event-related brain potentials (ERPs) were recorded. Attack
      images elicited enhanced P300 relative to negative and neutral images, and
      emotional images prompted larger slow waves than neutral images did. Total
      symptoms were correlated with altered N2, P300, and slow wave responses during
      valence processing. Specifically, hyperarousal and intrusion symptoms were
      associated with diminished stimulus discrimination between neutral and unpleasant
      images; avoidance symptoms were associated with hypervigilance, as suggested by
      reduced P300 difference between attack and other images and reduced appraisal of
      attack images as indicated by attenuated slow wave. The findings in this
      minimally symptomatic sample are compatible with the alterations in cognition in
      the posttraumatic stress disorder (PTSD) literature and are consistent with a
      dimensional model of PTSD.

PMID- 21882250
TI  - Shared traumatic stress and the long-term impact of 9/11 on Manhattan clinicians.
AB  - A sample of 481 social workers from Manhattan participated in a study of the
      impact of the September 11, 2001 (9/11) World Trade Center (WTC) attacks. A
      variety of risk factors associated with posttraumatic stress and secondary trauma
      were examined in relation to shared traumatic stress (STS), a supraordinate
      construct reflecting the dual nature of exposure to traumatic events. Risk
      factors included attachment style, exposure to potentially traumatic life events,
      and enduring distress attributed to the WTC attacks. It was expected that
      clinicians' resilience would mediate the relationship between these risk factors
      and STS. Using path analytic modeling, the findings support the study's
      hypotheses that insecure attachment, greater exposure to potentially traumatic
      life events in general, and the events of 9/11 in particular are predictive of
      higher levels of STS. Contrary to expectation, enduring distress attributed to
      9/11 was not associated with resilience. Resilience, however, was found to be a
      mediator of the relationships between insecure attachment, exposure to
      potentially traumatic life events, and STS but did not mediate the relationship
      between enduring distress attributed to 9/11 and STS. Implications for theory,
      research, and practice are discussed.

PMID- 21882251
TI  - Media use by children and adolescents from New York City 6 months after the WTC
      attack.
AB  - Six months after the World Trade Center (WTC) attacks of September 11, 2001
      (9/11), a representative sample of New York City students (N = 8,236) in Grades 4
      through 12 reported their use of TV, Web, and combined radio and print media
      regarding the WTC attack. Demographic factors, WTC exposure, other exposure to
      trauma, and probable posttraumatic stress disorder (PTSD) were used to predict
      intensive use of the 3 types of media. Intensive use was associated with direct
      exposure to the WTC attack (with the exception of Web use) and to having reported
      symptoms of PTSD. Stratified analyses indicated that the association between
      probable PTSD and intensive media use was more consistently present among those
      who had no direct or familial exposure to the WTC attack. As well, media,
      particularly TV, was intensively used by children after the WTC attack.
      Variations existed in the factors associated with intensive media use, which
      should be considered when planning postdisaster media coverage and advising
      families.

PMID- 21882252
TI  - Green tea catechin extract in intervention of chronic breast cell carcinogenesis
      induced by environmental carcinogens.
AB  - Sporadic breast cancers are mainly attributable to long-term exposure to
      environmental factors, via a multi-year, multi-step, and multi-path process of
      tumorigenesis involving cumulative genetic and epigenetic alterations in the
      chronic carcinogenesis of breast cells from a non-cancerous stage to precancerous
      and cancerous stages. Epidemiologic and experimental studies have suggested that
      green tea components may be used as preventive agents for breast cancer control.
      In our research, we have developed a cellular model that mimics breast cell
      carcinogenesis chronically induced by cumulative exposures to low doses of
      environmental carcinogens. In this study, we used our chronic carcinogenesis
      model as a target system to investigate the activity of green tea catechin
      extract (GTC) at non-cytotoxic levels in intervention of cellular carcinogenesis
      induced by cumulative exposures to pico-molar 4-(methylnitrosamino)-1-(3-pyridyl)
      1-butanone (NNK) and benzo[a]pyrene (B[a]P). We identified that GTC, at a non
      cytotoxic, physiologically achievable concentration of 2.5 ug/mL, was effective
      in suppressing NNK- and B[a]P-induced cellular carcinogenesis, as measured by
      reduction of the acquired cancer-associated properties of reduced dependence on
      growth factors, anchorage-independent growth, increased cell mobility, and acinar
      conformational disruption. We also detected that intervention of carcinogen
      induced elevation of reactive oxygen species (ROS), increase of cell
      proliferation, activation of the ERK pathway, DNA damage, and changes in gene
      expression may account for the mechanisms of GTC's preventive activity. Thus, GTC
      may be used in dietary and chemoprevention of breast cell carcinogenesis
      associated with long-term exposure to low doses of environmental carcinogens.

PMID- 21882253
TI  - Celecoxib inactivates epithelial-mesenchymal transition stimulated by hypoxia
      and/or epidermal growth factor in colon cancer cells.
AB  - Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been reported to
      exert chemopreventive and antitumor effects on colon cancer, one of the most
      common solid epithelial malignancy worldwide. The aim of this study was to
      elucidate whether celecoxib may be able to affect epithelial-mesenchymal
      transition (EMT), a critical process involved in cancer cell invasiveness and
      metastasis and then proposed to be relevant for cancer progression. Human HT-29
      colon cancer cells were exposed to carefully controlled hypoxic conditions and/or
      epidermal growth factor (EGF) and then investigated for EMT changes and signal
      transduction pathways involved by using morphological, molecular, and cell
      biology techniques. Celecoxib inhibited basal and EGF-stimulated proliferation,
      hypoxia-related HIF-1alpha recruitment/stabilization as well as hypoxia- and EGF
      dependent activation of ERK and PI3K. Interestingly, celecoxib prevented EMT
      related changes, as shown by modifications of beta-catenin intracellular
      localization or vimentin and E-cadherin levels, as well as HT-29 invasiveness
      induced by hypoxia, EGF, or hypoxia plus EGF. Finally, experiments performed on
      SW-480 colon cancer cells (i.e., cells lacking COX-2) exposed to hypoxia, used
      here as a stimulus able to induce EMT and invasiveness, revealed that in these
      cells celecoxib was ineffective. Results of the present study indicate that
      celecoxib has the potential to negatively affect induction of EMT and increased
      invasiveness of colon cancer cells as elicited by different signals originating
      from tumor microenvironment (i.e., hypoxia and EGF). Moreover, these effects are
      likely be related to the pharmacological inhibitory effect exerted on COX-2
      activity.

PMID- 21882254
TI  - PAX3-FOXO1 and FGFR4 in alveolar rhabdomyosarcoma.
AB  - We and others have identified FGFR4 as a direct transcriptional target of the
      alveolar rhabdomyosarcoma (ARMS) specific fusion protein, PAX3-FOXO1. We
      hypothesized fibroblast growth factor receptor 4 (FGFR4) may act as an effector
      of PAX3-FOXO1, contributing to PAX3-FOXO1 tumorigenic phenotypes. However, we
      demonstrate that enhanced expression of FGFR4 does not contribute to inhibited
      differentiation, enhanced proliferation, or transformation downstream of PAX3
      FOXO1 in primary mouse myoblasts. Therefore we were unable to identify any
      contribution of up regulation of wild type FGFR4 to PAX3-FOXO1 driven
      tumorigenesis. Conversely, a constitutively active mutant of FGFR4 can enhance
      primary myoblast proliferation and transformation, indicating activating
      mutations of FGFR4 could contribute to the development and progression of ARMS.
      We sequenced the FGFR4 mRNA from five ARMS cell lines and identified no somatic
      mutations, nor any association with any human single nucleotide polymorphism
      within the FGFR4 coding region.

PMID- 21882255
TI  - Ras inhibition in hepatocarcinoma by S-trans-trans-farnesylthiosalicyclic acid:
      association of its tumor preventive effect with cell proliferation, cell cycle
      events, and angiogenesis.
AB  - Activation of Ras and its downstream signaling pathways, likely contribute to the
      development of hepatocarcinoma. We have previously shown that intraperitoneal
      injections of the Ras inhibitor S-trans, trans-farnesylthiosalicyclic acid (FTS)
      blocks Ras activation and prevents heptocarcinoma development in rats receiving
      weekly injections of the carcinogene diethylnitrosamine (DEN) for 16 wk. Using
      this in vivo model, we evaluated the relationship between the tumor preventive
      effect of Ras inhibition and activation of downstream signaling pathways, cell
      proliferation, cell cycle events, and angiogenesis. Western blotting,
      quantitative PCR, immunohistochemistry, and transcription factor activity assays
      were used. DEN-induced activation of NFkB and Stat3 was abrogated by FTS
      treatment. FTS treatment showed no effect on DEN-induced elevation of TNFalpha,
      interleukin 6 and TLR4, known activators of these transcription factors. FTS
      significantly reduced phosphorylation of the MAPkinase p38 and of the p70S6
      kinase, a surrogate marker for mTor activation, without affecting ERK and AKT
      phosphorylation. These events were associated with reduced c-myc and cyclin D
      expression as well as reduced cell proliferation in transformed, GSTp-positive
      hepatocytes. Moreover, FTS treatment shifted cell proliferation from transformed
      hepatocytes to apparently normal, GSTp negative hepatocytes. FTS treatment did
      not down-regulate expression of angiogenesis markers HIFalpha, VEGF, VEGF
      receptor1, and placenta growth factor. FTS treatment inhibits important signaling
      pathways involved in cellular proliferation leading to strongly reduced
      proliferation of transformed hepatocytes without affecting normal hepatocytes.
      This re-adjustment of the proliferation balance likely contributes to the tumor
      preventive of FTS in the context of Ras inhibition in hepatocarcinogenesis.

PMID- 21882256
TI  - PPP2R1A mutations are common in the serous type of endometrial cancer.
AB  - Recently unbiased sequencing efforts identified PPP2R1A mutations in clear cell
      ovarian cancers (OCC). Similar mutations were also noted with high frequency in
      uterine serous carcinoma. Because the endometrium develops from the same
      developmental precursors we further examined the hypothesis that PPP2R1A
      mutations might also occur in diverse histologic subtypes of uterine cancer. We
      sequenced the PPP2R1A in 22 cell line models of uterine cancer and 10 primary
      cancers. We found no mutations in the cell lines originally derived from
      endometrioid (n = 13), undifferentiated (n = 3), clear cell (n = 1), and
      carcinosarcoma (n = 3) cancers. However, we found a CCC (Pro) to CGC (Arg) codon
      179 mutation in the ACI-158 serous carcinoma cell line, a CCC (Pro) to CTC (Leu)
      in a primary serous carcinoma as well as a CGC (Arg) to CAC (His) codon 258
      mutation in a poorly differentiated endometrioid cancer. We sequenced a large
      panel of endometrial malignancies (n = 181) and found 12 mutants. Importantly, we
      confirmed a high frequency of mutation in 8 of 25 (32%) serous carcinomas a
      subtype with well-recognized poor prognosis. Mutations were infrequent in
      endometrioid cancer and absent in clear cell and carcinosarcoma subtypes. The
      PPP2R1A mutation regions are conserved among species and known to interact with
      the regulatory subunits of the PP2A enzyme. PPP2R1A mutant endometrial cancers
      may represent good candidates for personalized drug therapies particularly for
      women with the lethal serous histologic variant of uterine cancer.

PMID- 21882257
TI  - Silibinin modulates TNF-alpha and IFN-gamma mediated signaling to regulate COX2
      and iNOS expression in tumorigenic mouse lung epithelial LM2 cells.
AB  - Silibinin inhibits mouse lung tumorigenesis in part by targeting tumor
      microenvironment. Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma
      (IFN-gamma) can be pro- or anti-tumorigenic, but in lung cancer cell lines they
      induce pro-inflammatory enzymes cyclooxygenase 2 (COX2) and inducible nitric
      oxide synthase (iNOS). Accordingly, here we examined mechanism of silibinin
      action on TNF-alpha + IFN-gamma (hereafter referred as cytokine mixture) elicited
      signaling in tumor-derived mouse lung epithelial LM2 cells. Both signal
      transducers and activators of the transcription (STAT)3 (tyr705 and ser727) and
      STAT1 (tyr701) were activated within 15 min of cytokine mixture exposure, while
      STAT1 (ser727) activated after 3 h. Cytokine mixture also activated Erk1/2 and
      caused an increase in both COX2 and iNOS levels. Pretreatment of cells with a
      MEK, NF-kappaB, and/or epidermal growth factor receptor (EGFR) inhibitor
      inhibited cytokine mixture-induced activation of Erk1/2, NF-kappaB, or EGFR,
      respectively, and strongly decreased phosphorylation of STAT3 and STAT1 and
      expression of COX2 and iNOS. Also, janus family kinases (JAK)1 and JAK2
      inhibitors specifically decreased cytokine-induced iNOS expression, suggesting
      possible roles of JAK1, JAK2, Erk1/2, NF-kappaB, and EGFR in cytokine mixture
      caused induction of COX2 and iNOS expression via STAT3/STAT1 activation in LM2
      cells. Importantly, silibinin pretreatment inhibited cytokine mixture-induced
      phosphorylation of STAT3, STAT1, and Erk1/2, NF-kappaB-DNA binding, and
      expression of COX2, iNOS, matrix metalloproteinases (MMP)2, and MMP9, which was
      mediated through impairment of STAT3 and STAT1 nuclear localization. Silibinin
      also inhibited cytokine mixture-induced migration of LM2 cells. Together, we
      showed that STAT3 and STAT1 could be valuable chemopreventive and therapeutic
      targets within the lung tumor microenvironment in addition to being targets
      within tumor itself, and that silibinin inhibits their activation as a plausible
      mechanism of its efficacy against lung cancer.

PMID- 21882258
TI  - Loss of Trp53 promotes medulloblastoma development but not skin tumorigenesis in
      Sufu heterozygous mutant mice.
AB  - Basal cell carcinoma of the skin typically carries genetic alterations in
      components of the hedgehog (HH) signaling pathway. Previously, we generated a
      knockout mouse with a loss-of-function mutation in suppressor of fused (Sufu), an
      essential repressor of the pathway downstream of Hh ligand cell surface
      reception. Mice heterozygous for the mutated Sufu allele develop a skin phenotype
      that includes lesions similar to basaloid follicular hamartomas. The purpose of
      the current study was to test the possibility that the simultaneous loss of the
      tumor suppressor gene, transformation related protein 53 (Trp53), would aggravate
      the Sufu skin phenotype since Trp53 loss is known to enhance the growth of other
      Hh-driven tumors. Consistent with previous reports, medulloblastomas and
      rhabdomyosarcomas developed in Sufu(+/-) ;Trp53(-/-) mice. However, the
      characteristic Sufu(+/-) skin phenotype was not altered in the absence of Trp53,
      and showed no changes in latency, multiplicity, cellular phenotype, or
      proliferative capacity of the basaloid lesions. This finding was both novel and
      intriguing and demonstrated a differential, tissue-specific sensitivity to Sufu
      and Trp53 tumor suppressor gene loss, which may be linked to developmental stage
      and the degree of proliferative activity in specific cell types.

PMID- 21882259
TI  - Down-regulation of Connexin43 expression reveals the involvement of caveolin-1
      containing lipid rafts in human U251 glioblastoma cell invasion.
AB  - Glioblastoma cells are characterized by high proliferation and invasive
      capacities. Tumor development has been associated with a decrease of gap
      junctional intercellular communication, but the concrete involvement of gap
      junction proteins, connexins, remains elusive since they are also suspected to
      promote cell invasion. In order to better understand how connexins control the
      glioma cell phenotype, we studied the consequences of inhibiting the intrinsic
      expression of the major astrocytic connexin, Connexin43, in human U251
      glioblastoma cells by the shRNA strategy. The induced down-regulation of Cx43
      expression has various effects on the U251 cells such as increased clonogenicity,
      angiogenesis and decreased adhesion on specific extracellular matrix proteins. We
      demonstrate that the invasion capacity measured in vitro and ex vivo correlates
      with Cx43 expression level. For the first time in a cancer cell context, our work
      demonstrates that Cx43 cofractionates, colocalizes and coimmunoprecipitates with
      a lipid raft marker, caveolin-1 and that this interaction is inversely correlated
      to the level of Cx43. This localization of Cx43 in these lipid raft microdomains
      regulates both homo- and heterocellular gap junctional communications
      (respectively between U251 cells, or between U251 cells and astrocytes).
      Moreover, the adhesive and invasive capacities are not dependent, in our model,
      on Cav-1 expression level. Our results tend to show that heterocellular gap
      junctional communication between cancer and stroma cells may affect the behavior
      of the tumor cells. Altogether, our data demonstrate that Cx43 controls the tumor
      phenotype of glioblastoma U251 cells and in particular, invasion capacity,
      through its localization in lipid rafts containing Cav-1.

PMID- 21882260
TI  - Interleukin-8 derived from local tissue-resident stromal cells promotes tumor
      cell invasion.
AB  - The aim of this study is to evaluate the role of adipose tissue resident stromal
      cells on tumor cell invasion. Our data show that a subpopulation of adipose
      tissue derived stromal cells expressing Nestin, NG2, alpha-smooth muscle actin
      and PDGFR-alpha migrate toward the cancer cells. Microarray analysis revealed the
      upregulation of IL-8 in the migrated cells. We demonstrated that stromal cell
      derived IL-8 promote the invasion and the anchorage-independent growth of cancer
      cells. We conclude that human breast cancer cells attract a subpopulation of
      stromal cells that secrete IL-8 to promote tumor cell invasion in a paracrine
      fashion.

PMID- 21882261
TI  - Cu-Si nanocable arrays as high-rate anode materials for lithium-ion batteries.

PMID- 21882262
TI  - Continuous patterning of nanogratings by nanochannel-guided lithography on liquid
      resists.

PMID- 21882263
TI  - Aptamer-mediated efficient capture and release of T lymphocytes on nanostructured
      surfaces.

PMID- 21882264
TI  - Transfer-free growth of few-layer graphene by self-assembled monolayers.

PMID- 21882265
TI  - Textured fluorine-doped tin dioxide films formed by chemical vapour deposition.
AB  - The use of an aerosol delivery system enabled fluorine-doped tin dioxide films to
      be formed from monobutyltin trichloride methanolic solutions at 350-550  degrees
      C with enhanced functional properties compared with commercial standards. It was
      noted that small aerosol droplets (0.3 MUm) gave films with better figures of
      merit than larger aerosol droplets (45 MUm) or use of a similar precursor set
      using atmospheric pressure chemical vapour deposition (CVD) conditions. Control
      over the surface texturing and physical properties of the thin films were
      investigated by variation in the deposition temperature and dopant concentration.
      Optimum deposition conditions for low-emissivity coatings were found to be at a
      substrate temperature of about 450  degrees C with a dopant concentration of 1.6
      atm% (30 mol% F:Sn in solution), which resulted in films with a low visible light
      haze value (1.74%), a high charge-carrier mobility (25 cm(2) V s(-1)) and a high
      charge-carrier density (5.7*10(20) cm(-3)) resulting in a high transmittance
      across the visible (~80%), a high reflectance in the IR (80% at 2500 nm) and
      plasma-edge onset at 1400 nm. Optimum deposition conditions for coatings with
      applications as top electrodes in thin film photovoltaics were found to be a
      substrate temperature of about 500  degrees C with a dopant concentration of 2.2
      atm% (30 mol% F:Sn in solution), which resulted in films with a low sheet
      resistance (3 Omega sq(-1)), high charge-carrier density (6.4*10(20) cm(-3)), a
      plasma edge onset of 1440 nm and the films also showed pyramidal surface
      texturing on the micrometer scale which corresponded to a high visible light haze
      value (8%) for light scattering and trapping within thin film photovoltaic
      devices.

PMID- 21882266
TI  - Synthesis, structure, and physical properties of a partial pi-stacked phenalenyl
      based neutral radical molecular conductor.
AB  - We report the synthesis, crystallization, and solid-state characterization of the
      3,7-ethoxy-substituted spirobiphenalenyl-boron neutral radical 22. The radical is
      distinguished by its low disproportionation energy and one-dimensional structure.
      We show that our strategy of substitution of OEt group at the active positions of
      the phenalenyl units changes the crystal packing from its previously known OMe
      analogue and the solid-state properties are dictated by the partial pi-stack
      structure and the oxygen atoms at the 3,7-positions and can be best rationalized
      in terms of the resonating valence bond model. Magnetic susceptibility
      measurements show that in the solid state the radical remains paramagnetic but
      there is significant spin-spin interaction between the molecules. Band structure
      calculations reflect efficient overlap between the molecules along the pi stack
      and show evidence of interactions between the spin-bearing oxygen atoms. The room
      temperature electrical conductivity (sigma(RT)=2.0*10(-2) S cm(-1)) of 22 is
      higher than that observed in previously known one-dimensional phenalenyl
      radicals.

PMID- 21882267
TI  - Probing spin density and local structure in the Prussian blue analogues
      CsCd[Fe/Co(CN)6].0.5H2O and Cd3[Fe/Co(CN)6]2.15H2O with solid-state MAS NMR
      spectroscopy.
AB  - Magic-angle spinning (MAS) NMR spectroscopy is used to study the local structure
      and spin delocalisation in Prussian blue analogues (PBAs). We selected two common
      archetypes of PBAs (A(I)M(II)[M(III)(CN)(6)].xH(2)O and
      M(II)(3)[M(III)(CN)(6)](2).xH(2)O, in which A(I) is an alkali ion, and M(II) and
      M(III) are transition-metal ions) that exhibit similar cubic frameworks but
      different microscopic structures. Whereas the first type of PBA contains
      interstitial alkali ions and does not exhibit any [M(III)(CN)(6)](3-) vacancies,
      the second type of PBA exhibits [M(III)(CN)(6)](3-) vacancies, but does not
      contain inserted alkali ions. In this study, we selected Cd(II) as a divalent
      metal in order to use the (113)Cd nuclei (I=1/2) as a probe of the local
      structure. Here, we present a complete MAS NMR study on two series of PBAs of the
      formulas Cd(II)(3)[Fe(III)(x)Co(III)(1-x)(CN)(6)](2).15H(2)O with x=0 (1), 0.25
      (2), 0.5 (3), 0.75 (4) and 1 (5), and CsCd(II)[Fe(III)(x)Co(III)(1
      x)(CN)(6)].0.5H(2)O with x=0 (6), 0.25 (7), 0.5 (8), 0.75 (9) and 1 (10).
      Interestingly, the presence of Fe(III) magnetic centres in the vicinity of the
      cadmium sites has a magnifying-glass effect on the NMR spectrum: it induces a
      striking signal spread such that the resolution is notably improved compared to
      that achieved for the diamagnetic PBAs. By doping the sample with varying amounts
      of diamagnetic Co(III) and comparing the NMR spectra of both types of PBAs, we
      have been able to give a view of the structure which is complementary to that
      usually obtained from X-ray diffraction studies. In particular, this study has
      shown that the vacancies are not randomly distributed in the mesoporous PBAs.
      Moreover the cadmium chemical shift, which is a measure of the hyperfine
      coupling, allows the estimation of the spin density on the cadmium nucleus, and
      consequently, the elucidation of the spin delocalisation mechanism in these
      compounds along with its dependency on structural parameters.

PMID- 21882268
TI  - Tuning of the electronic properties of a cyclopentadienylruthenium catalyst to
      match racemization of electron-rich and electron-deficient alcohols.
AB  - The synthesis of a new series of cyclopentadienylruthenium catalysts with varying
      electronic properties and their application in racemization of secondary alcohols
      are described. These racemizations involve two key steps: 1) beta-hydride
      elimination (dehydrogenation) and 2) re-addition of the hydride to the
      intermediate ketone. The results obtained confirm our previous theory that the
      electronic properties of the substrate determine which of these two steps is rate
      determining. For an electron-deficient alcohol the rate-determining step is the
      beta-hydride elimination (dehydrogenation), whereas for an electron-rich alcohol
      the re-addition of the hydride becomes the rate-determining step. By matching the
      electronic properties of the catalyst with the electronic properties of the
      alcohol, we have now shown that a dramatic increase in racemization rate can be
      obtained. For example, electron-deficient alcohol 15 racemized 30 times faster
      with electron-deficient catalyst 6 than with the unmodified standard catalyst 4.
      The application of these protocols will extend the scope of
      cyclopentadienylruthenium catalysts in racemization and dynamic kinetic
      resolution.

PMID- 21882269
TI  - Noncovalent one-to-one donor-acceptor assembled systems based on porphyrin
      molecular gels for unusually high electron-transfer efficiency.
AB  - A new approach for fabricating donor-acceptor assembled systems is demonstrated,
      based on J-type ordered aggregation of a low-molecular zinc porphyrin derivative
      and subsequent integration of a pyridylated fullerene derivative with
      coordination and orientation onto the porphyrin aggregates. This system achieves
      unusually high efficiencies in fluorescence quenching during one-to-one mixing of
      the donor and acceptor. Moreover, the Stern-Volmer constant (K(SV)) and
      association constant (K) of this system are 2520 and 56 times higher,
      respectively, than those of the corresponding nonassembled system. The quenching
      efficiency is thermotropically switchable, since ordered-to-disordered
      transitions are essential characteristics of noncovalent low molecular
      assemblies.

PMID- 21882270
TI  - Controlled rearrangement of lactam-tethered allenols with brominating reagents: a
      combined experimental and theoretical study on alpha- versus beta-keto lactam
      formation.
AB  - N-Bromosuccinimide (NBS) smoothly promotes the ring expansion of lactam-tethered
      allenols to efficiently afford cyclic alpha- or beta-ketoamides with good yields
      and high chemo-, regio-, and diastereoselectivity, through controlled C-C bond
      cleavage of the beta- or gamma-lactam nucleus. Interestingly, in contrast to the
      rearrangement reactions of 2-azetidinone-tethered allenols, which lead to the
      corresponding tetramic acid derivatives (beta-keto lactam adducts) as the sole
      products, the reactions of 2-indolinone-tethered allenols under similar
      conditions give quinoline-2,3-diones (alpha-keto lactam adducts) as the exclusive
      or major products. To rationalize the experimental observations, theoretical
      studies have been performed.

PMID- 21882271
TI  - Cycloaddition reactions: a controlled approach for carbon nanotube
      functionalization.
AB  - Controlled functionalization of carbon nanotubes (CNTs) through the use of
      cycloaddition reactions is described. By employing various cycloaddition
      reactions, a wide range of molecules could be coupled onto CNTs without
      disruption of the structural integrity as well as with a statistical distribution
      of functional groups onto the surface of the CNTs. The cycloaddition reactions
      represent an effective and tailored approach for preparing CNT-based advanced
      hybrid materials that would be useful for a wide range of applications from
      nanobiotechnology to nanoelectronics.

PMID- 21882273
TI  - Conjugated 4-methoxybipyrrole thiophene azomethines: synthesis, opto-electronic
      properties, and crystallographic characterization.
AB  - In the search of functional materials with improved electrochromic properties,
      thiophenes and asymmetric bipyrroles have been conjugated with azomethine units.
      4-Methoxy-2,2'-bipyrroles 3-6 were first synthesized by a general route from 4
      hydroxyproline and converted subsequently to dialdehydes 8-15, which underwent
      condensations with different aminothiophenes to provide azomethine conjugates 14
      18 and 20-22. The crystallization and X-ray analysis of 20 showed the
      heterocycles and azomethine bonds were all co-planar with the heterocycles
      adopting an anti-parallel arrangement. These configurations result in extended
      conjugation and enhanced opto-electronic properties of the azomethines. Oxidation
      potential (E(pa)) was tailored by modification of the substitution pattern of the
      terminal thiophenes and central pyrroles of the azomethines. The combined low
      E(pa) and extended azomethine degree of conjugation resulted in stark color
      transitions occurring between their neutral and oxidized states. Reversible color
      formation was induced both electrochemically and by doping/de-doping with
      trifluoroacetic acid/triethylamine.

PMID- 21882272
TI  - Biomolecule-assisted route to prepare titania mesoporous hollow structures.
AB  - Amino acids, as a particularly important type of biomolecules, have been used as
      multifunctional templates to intelligently construct mesoporous TiO(2) hollow
      structures through a simple solvothermal reaction. The structure-directing
      behaviors of various amino acids were systematically investigated, and it was
      found that these biomolecules possess the general capability to assist mesoporous
      TiO(2) hollow-sphere formation. At the same time, the nanostructures of the
      obtained TiO(2) are highly dependent on the isoelectric points (pI) of amino
      acids. Their molecular-structure variations can lead to pI differences and
      significantly influence the final TiO(2) morphologies. Higher-pI amino acids
      (e.g., L-lysine and L-arginine) have better structure-directing abilities to
      generate nanosheet-assembled hollow spheres and yolk/shell structures. The
      specific morphologies and mesopore size of these novel hollow structures can also
      be tuned by adjusting the titanium precursor concentration. Heat treatment in air
      and vacuum was further conducted to transform the as-prepared structures to
      porous nanoparticle-assembled hollow TiO(2) and TiO(2)/carbon nanocomposites,
      which may be potentially applied in the fields of photocatalysts, dye-sensitized
      solar cells, and Li batteries. This study provides some enlightenment on the
      design of novel templates by taking advantage of biomolecules.

PMID- 21882274
TI  - In situ phosphine oxide reduction: a catalytic Appel reaction.
AB  - Several important reactions in organic chemistry thrive on stoichiometric
      formation of phosphine oxides from phosphines. To avoid the resulting burden of
      waste and purification, cyclic phosphine oxides were evaluated for new catalytic
      reactions based on in situ regeneration. First, the ease of silane-mediated
      reduction of a range of cyclic phosphine oxides was explored. In addition, the
      compatibility of silanes with electrophilic halogen donors was determined for
      application in a catalytic Appel reaction based on in situ reduction of
      dibenzophosphole oxide. Under optimized conditions, alcohols were effectively
      converted to bromides or chlorides, thereby showing the relevance of new catalyst
      development and paving the way for broader application of organophosphorus
      catalysis by in situ reduction protocols.

PMID- 21882275
TI  - Polystyrene-supported diarylprolinol ethers as highly efficient organocatalysts
      for Michael-type reactions.
AB  - alpha,alpha-Diphenylprolinol methyl- and trimethylsilyl ethers anchored onto a
      polystyrene resin have been prepared by a copper-catalyzed azide-alkyne
      cycloadditions (CuAAC). The catalytic activity and enantioselectivity displayed
      by the O-trimethylsilyl derivative are comparable to those exhibited by the best
      known homogeneous catalysts for the addition of aldehydes to nitroolefins and of
      malonates or nitromethane to alpha,beta-unsaturated aldehydes. The combination of
      the catalytic unit, the triazole linker, and the polymeric matrix provides
      unprecedented substrate selectivity, in favor of linear, short-chain aldehydes,
      when the organocatalyzed reaction proceeds by an enamine mechanism. High
      versatility is noted in reactions that proceed via an iminium ion intermediate.
      The catalytic behavior of polystyrene-supported alpha,alpha-diphenylprolinol
      methyl ether was also evaluated in asymmetric Michael addition reactions. As a
      general trend, the CuAAC immobilization of diarylprolinol ethers onto insoluble
      polystyrene resins offers important operational advantages, such as high
      catalytic activity, easy recovery from the reaction mixture by simple filtration,
      and the possibility of extended reuse.

PMID- 21882276
TI  - Cu(I)/H2/NaOH-catalyzed cross-coupling of two different alcohols for carbon
      carbon bond formation: "borrowing hydrogen"?

PMID- 21882277
TI  - Visible-near-infrared and fluorescent copper sensors based on julolidine
      conjugates: selective detection and fluorescence imaging in living cells.
AB  - We present novel Schiff base ligands julolidine-carbonohydrazone 1 and julolidine
      thiocarbonohydrazone 2 for selective detection of Cu(2+) in aqueous medium. The
      planar julolidine-based ligands can sense Cu(2+) colorimetrically with
      characteristic absorbance in the near-infrared (NIR, 700-1000 nm) region.
      Employing molecular probes 1 and 2 for detection of Cu(2+) not only allowed
      detection by the naked eye, but also detection of varying micromolar
      concentrations of Cu(2+) due to the appearance of distinct coloration. Moreover,
      Cu(2+) selectively quenches the fluorescence of julolidine-thiocarbonohydrazone 2
      among all other metal ions, which increases the sensitivity of the probe.
      Furthermore, quenched fluorescence of the ligand 2 in the presence of Cu(2+) was
      restored by adjusting the complexation ability of the ligand. Hence, by treatment
      with ethylenediaminetetraacetic acid (EDTA), thus enabling reversibility and dual
      check signaling, julolidine-thiocarbonohydrazone (2) can be used as a fluorescent
      molecular probe for the sensitive detection of Cu(2+) in biological systems. The
      ligands 1 and 2 can be utilized to monitor Cu(2+) in aqueous solution over a wide
      pH range. We have investigated the structural, electronic, and optical properties
      of the ligands using ab initio density functional theory (DFT) combined with time
      dependent density functional theory (TDDFT) calculations. The observed absorption
      band in the NIR region is attributed to the formation of a charge-transfer
      complex between Cu(2+) and the ligand. The fluorescence-quenching behavior can be
      accounted for primarily due to the excited-state ligand 2 to metal (Cu(2+))
      charge-transfer (LMCT) processes. Thus, experimentally observed characteristic
      NIR and fluorescence optical responses of the ligands upon binding to Cu(2+) are
      well supported by the theoretical calculations. Subsequently, we have employed
      julolidine-thiocarbonohydrazone 2 for reversible fluorescence sensing of
      intracellular Cu(2+) in cultured HEK293T cells.

PMID- 21882278
TI  - Highly enantioselective rhodium-catalyzed asymmetric 1,4-addition reactions of
      arylboronic acids to acyclic alpha,beta-unsaturated compounds: the formal
      synthesis of (-)-indatraline.

PMID- 21882279
TI  - Heteroscorpionate rare-earth metal zwitterionic complexes: syntheses,
      characterization, and heteroselective catalysis on the ring-opening
      polymerization of rac-lactide.
AB  - Novel neutral phosphine-modified heteroscorpionate ligand (3,5
      Me(2)Pz)(2)CHPPh(2) (1) and its derivatives oxophosphine (2) and iminophosphine
      (3) heteroscorpionates were synthesized for the first time. These neutral
      heteroscorpionate ligands displayed unique chemistry towards rare-earth metal
      tris(alkyl)s [Ln(CH(2)SiMe(3))(3)(thf)(2)] (Ln=Y, Lu, Sc). The reaction between
      compound 1 and [Ln(CH(2)SiMe(3))(3)(thf)(2)] afforded heteroscorpionate rare
      earth metal trialkyl adduct complexes 4a-c. Compounds 2 and 3 were treated with
      [Ln(CH(2)SiMe(3))(3)(thf)(2)] to give the unprecedented zwitterionic
      heteroscorpionate rare-earth metal dialkyls 5 and 6, respectively. In the
      process, the heteroscorpionates transferred to the carbanions by means of methine
      C-H bond cleavage that was attributed to the presence of the electron-withdrawing
      groups. In addition the ligand and central metal showed a concerted effect on
      both the catalytic activity and specific selectivity of complexes 4-6 for the
      ring-opening polymerization (ROP) of rac-lactide (rac-LA). All the adduct
      complexes 4 were nonselective and gave atactic polylactide (PLA), probably due to
      the dissociation of ligand 1 from the active metal center during the
      polymerization. Strikingly, zwitterionic complexes 5 catalyzed rapid ROP of rac
      LA to produce PLAs with heterotacticity up to 0.87. However, the zwitterionic
      complexes 6 were less active and less selective than 5, which might be on account
      of the stronger coordination of the tetradentate ligand. Complexes 5 represent
      rare examples of the selective ROP of rac-LA mediated by rare-earth metal
      complexes supported by non-bisphenolate ligands.

PMID- 21882280
TI  - Enantioselective and regioselective Friedel-Crafts alkylation of pyrroles with
      nitroalkenes catalyzed by a tridentate Schiff base-copper complex.

PMID- 21882282
TI  - Molecular profiling reveals frequent gain of MYCN and anaplasia-specific loss of
      4q and 14q in Wilms tumor.
AB  - Anaplasia in Wilms tumor, a distinctive histology characterized by abnormal
      mitoses, is associated with poor patient outcome. While anaplastic tumors
      frequently harbour TP53 mutations, little is otherwise known about their
      molecular biology. We have used array comparative genomic hybridization (aCGH)
      and cDNA microarray expression profiling to compare anaplastic and favorable
      histology Wilms tumors to determine their common and differentiating features. In
      addition to changes on 17p, consistent with TP53 deletion, recurrent anaplasia
      specific genomic loss and under-expression were noted in several other regions,
      most strikingly 4q and 14q. Further aberrations, including gain of 1q and loss of
      16q were common to both histologies. Focal gain of MYCN, initially detected by
      high resolution aCGH profiling in 6/61 anaplastic samples, was confirmed in a
      significant proportion of both tumor types by a genomic quantitative PCR survey
      of over 400 tumors. Overall, these results are consistent with a model where
      anaplasia, rather than forming an entirely distinct molecular entity, arises from
      the general continuum of Wilms tumor by the acquisition of additional genomic
      changes at multiple loci.

PMID- 21882283
TI  - Microarray-based genomic profiling as a diagnostic tool in acute lymphoblastic
      leukemia.
AB  - In acute lymphoblastic leukemia (ALL) specific genomic abnormalities provide
      important clinical information. In most routine clinical diagnostic laboratories
      conventional karyotyping, in conjunction with targeted screens using e.g.,
      fluorescence in situ hybridization (FISH), is currently considered as the gold
      standard to detect such aberrations. Conventional karyotyping, however, is
      limited in its resolution and yield, thus hampering the genetic diagnosis of ALL.
      We explored whether microarray-based genomic profiling would be feasible as an
      alternative strategy in a routine clinical diagnostic setting. To this end, we
      compared conventional karyotypes with microarray-deduced copy number aberration
      (CNA) karyotypes in 60 ALL cases. Microarray-based genomic profiling resulted in
      a CNA detection rate of 90%, whereas for conventional karyotyping this was 61%.
      In addition, many small (< 5 Mb) genetic lesions were encountered, frequently
      harboring clinically relevant ALL-related genes such as CDKN2A/B, ETV6, PAX5, and
      IKZF1. From our data we conclude that microarray-based genomic profiling serves
      as a robust tool in the genetic diagnosis of ALL, outreaching conventional
      karyotyping in CNA detection both in terms of sensitivity and specificity. We
      also propose a practical workflow for a comprehensive and objective
      interpretation of CNAs obtained through microarray-based genomic profiling,
      thereby facilitating its application in a routine clinical diagnostic setting.

PMID- 21882281
TI  - 13C MRS studies of neuroenergetics and neurotransmitter cycling in humans.
AB  - In the last 25 years, (13)C MRS has been established as the only noninvasive
      method for the measurement of glutamate neurotransmission and cell-specific
      neuroenergetics. Although technically and experimentally challenging, (13)C MRS
      has already provided important new information on the relationship between
      neuroenergetics and neuronal function, the energy cost of brain function, the
      high neuronal activity in the resting brain state and how neuroenergetics and
      neurotransmitter cycling are altered in neurological and psychiatric disease. In
      this article, the current state of (13)C MRS as it is applied to the study of
      neuroenergetics and neurotransmitter cycling in humans is reviewed. The focus is
      predominantly on recent findings in humans regarding metabolic pathways,
      applications to clinical research and the technical status of the method. Results
      from in vivo (13)C MRS studies in animals are discussed from the standpoint of
      the validation of MRS measurements of neuroenergetics and neurotransmitter
      cycling, and where they have helped to identify key questions to address in human
      research. Controversies concerning the relationship between neuroenergetics and
      neurotransmitter cycling and factors having an impact on the accurate
      determination of fluxes through mathematical modeling are addressed. We further
      touch upon different (13)C-labeled substrates used to study brain metabolism,
      before reviewing a number of human brain diseases investigated using (13)C MRS.
      Future technological developments are discussed that will help to overcome the
      limitations of (13)C MRS, with special attention given to recent developments in
      hyperpolarized (13)C MRS.

PMID- 21882284
TI  - Response to regulatory stringency: the case of antipsychotic medication use in
      nursing homes.
AB  - This paper studies the impact of regulatory stringency, as measured by the
      statewide deficiency citation rate over the past year, on the quality of care
      provided in a national sample of nursing homes from 2000 to 2005. The quality
      measure used is the proportion of residents who are using antipsychotic
      medication. Although the changing case-mix of nursing home residents accounts for
      some of the increase in the use of antipsychotics, we find that the use of
      antipsychotics by nursing homes is responsive to state regulatory enforcement in
      a manner consistent with the multitasking incentive problem. Specifically, the
      effect of the regulations is dependent on the degree of complementarity between
      the regulatory deficiency and the use of antipsychotics.

PMID- 21882285
TI  - Accounting for between-study variation in incremental net benefit in value of
      information methodology.
AB  - Previous applications of value of information methods for determining optimal
      sample size in randomized clinical trials have assumed no between-study variation
      in mean incremental net benefit. By adopting a hierarchical model, we provide a
      solution for determining optimal sample size with this assumption relaxed. The
      solution is illustrated with two examples from the literature. Expected net gain
      increases with increasing between-study variation, reflecting the increased
      uncertainty in incremental net benefit and reduced extent to which data are
      borrowed from previous evidence. Hence, a trial can become optimal where current
      evidence is sufficient assuming no between-study variation. However, despite the
      expected net gain increasing, the optimal sample size in the illustrated examples
      is relatively insensitive to the amount of between-study variation. Further
      percentage losses in expected net gain were small even when choosing sample sizes
      that reflected widely different between-study variation.

PMID- 21882286
TI  - Matched and mismatched cognitive appraisals in patients with breast cancer and
      their partners: implications for psychological distress.
AB  - BACKGROUND: The present study sought to identify couples' cognitive appraisals of
      breast cancer and the extent to which matched or mismatched appraisals within a
      couple contribute to distress. METHODS: Women with breast cancer (n = 57) and
      their partners completed the Cognitive Appraisals of Health Scale along with two
      self-report measures of distress, the Profile of Mood States and the Impact of
      Events Scale. Four groups were created based on their cognitive appraisals.
      Couples where both patient and partner scored highest on challenge or benign
      appraisals formed the positive outlook group (P+S+); when both scored highest on
      threat or harm/loss, they formed the negative outlook group (P-S-). In the
      mismatched groups, the patient had a positive outlook, and their partner had a
      negative outlook (P+S-), or vice versa (P-S+). RESULTS: In general, lower
      distress was related to participants' own positive outlook. Higher distress for
      patients was found in the matched group P-S-; for partners, it was found in the
      mismatched group P+S-. CONCLUSIONS: These findings suggest partner effects for
      both patients and partners. When the patient had a negative outlook, a partner
      negative outlook was associated with the highest psychological distress. When the
      partner had a negative outlook, a patient positive outlook was associated with
      the highest psychological distress. There are several possible explanations for
      these findings, each with different implications for clinical practice. Future
      research with different groups of cancer patients and longitudinal, mixed methods
      designs may clarify their meaning.

PMID- 21882287
TI  - Psychological treatment outcomes for cancer patients: what do meta-analyses tell
      us about distress reduction?
AB  - OBJECTIVE: The effectiveness of psychological treatment for distress reduction in
      cancer patients has been frequently studied and reviewed in systematic reviews
      but reviewer conclusions vary considerably. Clear and consistent evidence is
      needed to assist clinicians and administrators with their decision-making. We
      hypothesized that uneven handling of confounding methodological features are at
      least partly the reason for disagreements and reviewed the literature in this
      light. METHOD: A systematic review of 14 published meta-analyses was conducted to
      determine whether due consideration of moderating variables in psycho-oncological
      treatments permits clearer recommendations. Quality of the reviews, treatment
      type, dosage, therapist qualities, outcomes at follow-up, and screening versus
      not screening for elevated distress were examined as moderator variables.
      RESULTS: Treatment effects are consistently positive but also vary greatly in
      magnitude. There is lacking evidence for many important questions, in particular,
      differential treatment effects for different cancer types and stages. Regarding
      moderators of outcome, quality of review had no impact on results for depression
      but including lower quality reviews actually lead to underestimation of treatment
      effects for anxiety. The most potent negative moderator variable, however, is a
      floor effect that arises when patients are recruited for treatment studies
      without being selected for high levels of distress. Such indiscriminate
      recruitment is very frequent in psycho-oncology and leads to small reported
      treatment effects; when, however, patients are first screened for elevated
      distress, the ratio of observed treatment effects sizes is roughly three times
      greater. CONCLUSION: Sweeping judgments about the effectiveness of psycho
      oncological treatments for distress reduction are somewhat misleading and counter
      productive. Among moderator variables, floor effects are particularly pervasive
      and have a large suppressor effect on observed outcomes.

PMID- 21882288
TI  - Differences in depressed oncologic patients' narratives after receiving two
      different therapeutic interventions for depression: a qualitative study.
AB  - BACKGROUND: This study aims to explore differences in personal narratives of the
      experience of illness and treatment in depressed oncologic patients who received
      either combined treatment for depression (psychotherapy plus antidepressants) or
      standard treatment (antidepressants alone). METHODS: We employed a qualitative
      research design based on grounded theory. Data were collected from eight
      videotaped focus groups and semi-structured interviews with a total of 28
      participants. The research team reviewed interview transcripts and categorized
      the participants' responses using the ATLAS.ti (ATLAS.ti Scientific Software
      Development GmbH Hardenbergstr. 7 D-10623, Berlin) software package. RESULTS:
      Compared with patients in the standard treatment group, patients in the combined
      treatment group were better able to relate their experiences of physical and
      emotional discomfort and find meaning in the experience of illness by viewing
      cancer as a transformative experience. In addition, patients in the combined
      treatment group tended to use more active coping strategies based on acceptance
      of their situation and emphasized that psychotherapy had been helpful.
      CONCLUSIONS: Qualitative analysis is an efficient method of examining the meaning
      of quantitative results in depth, particularly patients' perspectives on quality
      of life. Patients undergoing combined treatment consider psychotherapy to be a
      helpful tool and exhibit more personal growth than do patients undergoing
      standard treatment.

PMID- 21882289
TI  - A comparative analysis approach to determining the pathogenicity of mitochondrial
      tRNA mutations.
AB  - Distinguishing pathogenic from polymorphic changes poses significant problems for
      geneticists and despite 30 years of postgenomic experience this remains the case
      in mitochondrial genetics. Base substitutions in mitochondrial tRNA (mt-tRNA)
      genes are particularly difficult, but important, because they are common causes
      of pathology and associated with high rates of transmission. Providing accurate
      genetic advice to patients and their families is of paramount importance in
      disease prevention, and brings into sharp focus the factors used to distinguish
      pathogenic from polymorphic variants. We have reevaluated our pathogenicity
      scoring system for mt-tRNA mutations following a considerable increase in the
      number reported since the system was devised in 2004. This allowed us to address
      notable issues including the underestimation of "definitely pathogenic" mutations
      resulting from insufficient data collection. We illustrate the robustness of our
      revised scoring system using novel pathogenic and previously reported polymorphic
      changes and conclude that while clear evidence from single-fiber and/or trans
      mitochondrial cybrid studies remains the gold standard for assigning
      pathogenicity, our scoring system is valuable for deciding which mt-tRNA
      mutations to investigate further using these labor-intensive techniques.

PMID- 21882291
TI  - Large deletions of the KCNV2 gene are common in patients with cone dystrophy with
      supernormal rod response.
AB  - Cone dystrophy with supernormal rod response (CDSRR) is considered to be a very
      rare autosomal recessive retinal disorder. CDSRR is associated with mutations in
      KCNV2, a gene that encodes a modulatory subunit (Kv8.2) of a voltage-gated
      potassium channel. In this study, we found that KCNV2 mutations are present in a
      substantial fraction (2.2-4.3%) of a sample of 367 independent patients with a
      variety of initial clinical diagnoses of cone malfunction, indicating that CDSRR
      is underdiagnosed and more common than previously thought. In total, we
      identified 20 different KCNV2 mutations; 15 of them are novel. A new finding of
      this study is the substantial proportion of large deletions at the KCNV2 locus
      that accounts for 15.5% of the mutant alleles in our sample. We determined the
      breakpoints and size of all five different deletions, which ranged between 10.9
      and 236.8 kb. Two deletions encompass the entire KCNV2 gene and one also includes
      the adjacent VLDLR gene. Furthermore, we investigated N-terminal amino acid
      substitution mutations for its effect on interaction with Kv2.1 using yeast two
      hybrid technology. We found that these mutations dramatically reduce or abolish
      this interaction suggesting a lack of assembly of heteromeric Kv channels as one
      underlying pathomechanism of CDSRR.

PMID- 21882292
TI  - High frequency of rare copy number variants affecting functionally related genes
      in patients with structural brain malformations.
AB  - During the past years, significant advances have been made in our understanding
      of the development of the human brain, and much of this knowledge comes from
      genetic studies of disorders associated with abnormal brain development. We
      employed array-comparative genomic hybridization (CGH) to investigate copy number
      variants (CNVs) in a cohort of 169 patients with various structural brain
      malformations including lissencephaly, polymicrogyria, focal cortical dysplasia,
      and corpus callosum agenesis. The majority of the patients had intellectual
      disabilities (ID) and suffered from symptomatic epilepsy. We detected at least
      one rare CNV in 38 patients (22.5%). All genes located within the rare CNVs were
      subjected to enrichment analysis for specific Gene Ontology Terms or Kyoto
      Encyclopedia of Genes and Genomes pathways and to protein-protein network
      analysis. Based on these analyses, we propose that genes involved in "axonal
      transport," "cation transmembrane transporter activity," and the "c-Jun N
      terminal kinase (JNK) cascade" play a significant role in the etiology of brain
      malformations. This is to the best of our knowledge the first systematic study of
      CNVs in patients with structural brain malformations and our data show that CNVs
      play an important role in the etiology of these malformations, either as direct
      causes or as genetic risk factors.

PMID- 21882290
TI  - Evidence of association of APOE with age-related macular degeneration: a pooled
      analysis of 15 studies.
AB  - Age-related macular degeneration (AMD) is the most common cause of incurable
      visual impairment in high-income countries. Previous studies report inconsistent
      associations between AMD and apolipoprotein E (APOE), a lipid transport protein
      involved in low-density cholesterol modulation. Potential interaction between
      APOE and sex, and smoking status has been reported. We present a pooled analysis
      (n = 21,160) demonstrating associations between late AMD and APOepsilon4 (odds
      ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65-0.74; P =
      4.41*10(-11) ) and APOepsilon2 (OR = 1.83 for homozygote carriers; CI: 1.04-3.23;
      P = 0.04), following adjustment for age group and sex within each study and
      smoking status. No evidence of interaction between APOE and sex or smoking was
      found. Ever smokers had significant increased risk relative to never smokers for
      both neovascular (OR = 1.54; CI: 1.38-1.72; P = 2.8*10(-15) ) and atrophic (OR =
      1.38; CI: 1.18-1.61; P = 3.37*10(-5) ) AMD but not early AMD (OR = 0.94; CI: 0.86
      1.03; P = 0.16), implicating smoking as a major contributing factor to disease
      progression from early signs to the visually disabling late forms. Extended
      haplotype analysis incorporating rs405509 did not identify additional risks
      beyond epsilon2 and epsilon4 haplotypes. Our expanded analysis substantially
      improves our understanding of the association between the APOE locus and AMD. It
      further provides evidence supporting the role of cholesterol modulation, and low
      density cholesterol specifically, in AMD disease etiology.

PMID- 21882293
TI  - Extending the phenotypes associated with DICER1 mutations.
AB  - DICER1 is crucial for embryogenesis and early development. Forty different
      heterozygous germline DICER1 mutations have been reported worldwide in 42
      probands that developed as children or young adults, pleuropulmonary blastoma
      (PPB), cystic nephroma (CN), ovarian sex cord-stromal tumors (especially Sertoli
      Leydig cell tumor [SLCT]), and/or multinodular goiter (MNG). We report DICER1
      mutations in seven additional families that manifested uterine cervix embryonal
      rhabdomyosarcoma (cERMS, four cases) and primitive neuroectodermal tumor (cPNET,
      one case), Wilms tumor (WT, three cases), pulmonary sequestration (PS, one case),
      and juvenile intestinal polyp (one case). One carrier developed (age 25 years) a
      pleomorphic sarcoma of the thigh; another carrier had transposition of great
      arteries (TGA). These observations show that cERMS, cPNET, WT, PS, and juvenile
      polyps fall within the spectrum of DICER1-related diseases. DICER1 appears to be
      the first gene implicated in the etiology of cERMS, cPNET, and PS. Young
      adulthood sarcomas and perhaps congenital malformations such as TGA may also be
      associated.

PMID- 21882294
TI  - SgD-CNV, a database for common and rare copy number variants in three Asian
      populations.
AB  - Copy number variants (CNVs) extend our understanding of the genetic diversity in
      humans. However, the distribution and characteristics of CNVs in Asian
      populations remain largely unexplored, especially for rare CNVs that have emerged
      as important genetic factors for complex traits. In the present study, we
      performed an in-depth investigation of common and rare CNVs across 8,148
      individuals from the three major Asian ethnic groups: Chinese (n = 1,945), Malays
      (n = 2,399), and Indians (n = 2,217) in Singapore, making this investigation the
      most comprehensive genome-wide survey of CNVs outside the European-ancestry
      populations to date. We detected about 16 CNVs per individual and the ratio of
      loss to gain events is ~2:1. The majority of the CNVs are of low frequency
      (<10%), and 40% are rare (<1%). In each population, ~20% of the CNVs are not
      previously catalogued in the Database of Genomic Variants (DGV). Contrary to
      findings from European studies, the common CNVs (>5%) in our populations are not
      well tagged by SNPs in Illumina 1M and 610K arrays, and most disease-associated
      common CNVs previously reported in Caucasians are rare in our populations. We
      also report noticeable population differentiation in the CNV landscape of these
      Asian populations, with the greatest diversity seen between the Indians and the
      Chinese.

PMID- 21882295
TI  - Integrating theories and concepts: formulation driven CBT for a client with a
      diagnosis of schizo-affective disorder.
AB  - Therapists working with people who have complex problems associated with
      psychosis may find it difficult to apply currently available cognitive
      behavioural therapy (CBT) manuals to client's presenting problems. This can lead
      to activation of negative therapist beliefs about themselves, the client or the
      therapy and subsequent problems maintaining the therapeutic relationship. This
      paper describes the integration of a range of models and concepts derived from
      CBT which were used to assist one such client with complex problems associated
      with psychosis. As such, it is proposed that taking a flexible, formulation
      driven approach to therapy can assist therapists to remain client centred and
      work effectively. The therapy described draws on a number of concepts including
      those taken from schema focussed therapy, mindfulness and compassionate mind
      training. Therapist and client summary letters were used as part of the described
      intervention, but in addition, the client's summary is reproduced in the paper
      aiming to address the issue of the under reporting in the literature of the
      client's perspective on therapy.

PMID- 21882296
TI  - What basic emotions are experienced in bipolar disorder?
AB  - AIMS: The aims of this study were to investigate the basic emotions experienced
      within and between episodes of bipolar disorder and, more specifically, to test
      the predictions made by the Schematic, Propositional, Analogical and Associative
      Representation Systems (SPAARS) model that mania is predominantly characterized
      by the coupling of happiness with anger whereas depression (unipolar and bipolar)
      primarily comprises a coupling between sadness and disgust. DESIGN: A cross
      sectional design was employed to examine the differences within and between the
      bipolar, unipolar and control groups in the emotional profiles. Data were
      analysed using one-way ANOVAs. METHOD: Psychiatric diagnoses in the clinical
      groups were confirmed using the Structured Clinical Interview for DSM-IV (SCID).
      It was not administered in the control group. Current mood state was measured
      using the Beck Depression Inventory-II, the State-Trait Anxiety Inventory and the
      Bech-Rafaelsen Mania Scale. The Basic Emotions Scale was used to explore the
      emotional profiles. RESULTS: The results confirmed the predictions made by the
      SPAARS model about emotions in mania and depression. Outwith these episodes,
      individuals with bipolar disorder experienced elevated levels of disgust.
      DISCUSSION: Evidence was found in support of the proposal of SPAARS that there
      are five basic emotions, which form the basis for both normal emotional
      experience and emotional disorders. Disgust is an important feature of bipolar
      disorder. Strengths and limitations are discussed, and suggestions for future
      research are explored.

PMID- 21882297
TI  - Using plan analysis in psychotherapeutic case formulation of borderline
      personality disorder.
AB  - A comprehensive understanding of the patient's problems is essential for a
      constructive therapeutic behaviour, especially in borderline personality disorder
      (BPD) where difficult interpersonal patterns are persistent. In these
      circumstances, the use of an integrative case formulation approach such as Plan
      Analysis, developed by K. Grawe and F. Caspar, can be of help for therapy
      planning. The focus here is on instrumental relations between behaviours and the
      hypothetical Plans and motives 'behind' those behaviours. The present qualitative
      study aimed at setting a prototypical Plan structure for n = 15 patients
      presenting a Diagnostic and Statistical Manual of Mental Disorders, Fourth
      Edition, diagnosis of BPD using Plan Analysis. The first psychotherapeutic
      session of every outpatient was video-taped and evaluated according to the Plan
      Analysis procedure. Inter-rater reliability was established between two
      independent raters and was considered sufficient. The detailed prototypical Plan
      structure of BPD showed two main tendencies: first, the important presence of
      support-seeking among these patients and second, the will to be in control and to
      protect oneself. This study confirms the existence of several core similarities
      in the functioning of patients with BPD. These findings are in line with earlier
      studies and expand the latter with the aim of contributing to the understanding
      of BPD psychopathology. Clinical implications are discussed.

PMID- 21882298
TI  - Qualitative exploration of empowerment from the perspective of young people with
      psychosis.
AB  - Evidence suggests that empowerment is central to improving the effectiveness and
      quality of mental health care. Empowerment includes increased involvement, choice
      and access to health information for service users. Within the process of
      empowerment, individuals may better understand their health needs and accordingly
      improve their prognoses. Despite the widespread use of the term 'empowerment'
      within mental health, there have been no studies examining how young people with
      psychosis understand and conceptualize the term empowerment or which factors are
      conductive to them developing a sense of empowerment. This study aims to
      qualitatively conceptualize empowerment from the perspective of young people aged
      14-18 years experiencing psychosis. Individual interviews were conducted with
      nine young people with a diagnosis of a psychotic disorder regarding their
      understanding and experience of empowerment. The interviews were audiotaped,
      transcribed verbatim and analysed using interpretative phenomenological analysis.
      Results indicated that young people who have experienced psychosis conceptualized
      empowerment as being listened to, being understood, taking control and making
      decisions for themselves. Young people place high importance on experiencing
      personal empowerment in relation to being users of mental health services and
      regard being empowered as the most important factor for determining their own
      recovery. Results also revealed that young people view mental health workers as
      very variable in their ability and willingness to address and help facilitate
      empowerment. They also identified daily routine, structure and avoidance of
      inactivity as additional means of increasing empowerment. The implications for
      research and practice are discussed. KEY PRACTITIONER MESSAGE: The way
      practitioners interact with young people impacts upon their experience of
      empowerment. Young people with psychosis equate being listened to with being
      empowered. Young people with psychosis, especially when hospitalized, want to
      develop and use their own coping styles. Clinicians who give choices and have a
      sense of humour are valued by young people with psychosis. Clinicians must
      consider whose needs are being met when decisions are made for young people with
      psychosis.

PMID- 21882299
TI  - Role of medial cortical networks for anticipatory processing in obsessive
      compulsive disorder.
AB  - Recurrent anticipation of ominous events is central to obsessions, the core
      symptom of obsessive-compulsive disorder (OCD), yet the neural basis of intrinsic
      anticipatory processing in OCD is unknown. We studied nonmedicated adults with
      OCD and case matched healthy controls in a visual-spatial working memory task
      with distractor. Magnetoencephalography was used to examine the medial cortex
      activity during anticipation of to-be-inhibited distractors and to-be-facilitated
      retrieval stimuli. In OCD anticipatory activation to distractors was abnormally
      reduced within the posterior cingulate and fusiform gyrus compared to prominent
      activation in controls. Conversely, OCD subjects displayed significantly
      increased activation to retrieval stimuli within the anterior cingulate and
      supplementary motor cortex. This previously unreported discordant pattern of
      medial anticipatory activation in OCD was accompanied by normal performance
      accuracy. While increased anterior cortex activation in OCD is commonly viewed as
      failure of inhibition, the current pattern of data implicates the operation of an
      anterior compensatory mechanism amending the posterior medial self-regulatory
      networks disrupted in OCD.

PMID- 21882300
TI  - Evaluating and reducing the impact of white matter lesions on brain volume
      measurements.
AB  - MR-based measurements of brain volumes may be affected by the presence of white
      matter (WM) lesions. Here, we assessed how and to what extent this may happen for
      WM lesions of various sizes and intensities. After inserting WM lesions of
      different sizes and intensities into T1-W brain images of healthy subjects, we
      assessed the effect on two widely used automatic methods for brain volume
      measurement such as SIENAX (segmentation-based) and SIENA (registration-based).
      To explore the relevance of partial volume (PV) estimation, we performed the
      experiments with two different PV models, implemented by the same segmentation
      algorithm (FAST) of SIENAX and SIENA. Finally, we tested potential solutions to
      this issue. The presence of WM lesions did not bias measurements for registration
      based method such as SIENA. By contrast, the presence of WM lesions affected
      segmentation-based brain volume measurements such as SIENAx. The
      misclassification of both gray matter (GM) and WM volumes varied considerably
      with lesion size and intensity, especially when the lesion intensity was similar
      to that of the GM/WM interface. The extent to which the presence of WM lesions
      could affect tissue-class measures was clearly driven by the PV modeling used,
      with the mixel-type PV model giving a lower error in the presence of WM lesions.
      The tissue misclassification due to WM lesions was still present when they were
      masked out. By contrast, refilling the lesions with intensities matching the
      surrounding normal-appearing WM ensured accurate tissue-class measurements and
      thus represents a promising approach for accurate tissue classification and brain
      volume measurements.

PMID- 21882302
TI  - Platinum nanoparticles encapsulated by aminopeptidase: a multifunctional
      bioinorganic nanohybrid catalyst.

PMID- 21882301
TI  - Concomitant therapy with methotrexate and anti-TNF-alpha in pediatric patients
      with refractory crohn's colitis: a case series.
AB  - BACKGROUND: Crohn's colitis refractory to anti-tumor necrosis factor alpha (TNF
      alpha) therapy is commonly seen in tertiary care centers for pediatric
      inflammatory bowel disease (IBD). We report our experience in managing pediatric
      refractory Crohn's colitis with concomitant use of methotrexate and anti-TNF
      alpha therapy. METHODS: We reviewed records from 2007 to 2010 at the Mayo Clinic
      pediatric IBD center. We included all patients with Crohn's disease (CD) failing
      anti-TNF-alpha therapy who then received concomitant methotrexate. The primary
      endpoint was clinical remission, defined as inactive disease in accordance with
      the short pediatric CD activity index (PCDAI). The secondary endpoint was last
      day of follow-up. RESULTS: Fourteen patients with CD received concomitant
      methotrexate and anti-TNF-alpha treatment (age, mean [range], 15.7 [6-20] years;
      standard deviation [SD], 3.4 years). Mean age at diagnosis was 12.5 years (range,
      3-17 years; SD, 3.83 years). The male-to-female ratio was 10:4. All patients had
      moderate to severe disease activity using the short PCDAI and had predominately
      Crohn's colitis. Twelve patients were previously treated with thiopurines
      (85.7%). Seven patients (50%) were in clinical remission within an average of 6
      weeks postmethotrexate induction. Five patients (35.7%) experienced adverse
      events including nausea and headache, yet only one discontinued therapy due to
      adverse events. Infection with Clostridium difficile was common, complicating
      therapy in four patients (28.6%). CONCLUSIONS: Concomitant use of methotrexate
      and anti-TNF-alpha therapy is a promising option for children with refractory
      Crohn's colitis.

PMID- 21882303
TI  - Direct correlation between local pressure and fluorescence output in
      mechanoresponsive polyelectrolyte brushes.

PMID- 21882304
TI  - Mixed-metal lanthanide-iron triple-decker complexes with a cyclo-P5 building
      block.

PMID- 21882305
TI  - Multifunctional nanoprobes for nanoscale chemical imaging and localized chemical
      delivery at surfaces and interfaces.

PMID- 21882307
TI  - Germanium nanotubes prepared by using the Kirkendall effect as anodes for high
      rate lithium batteries.

PMID- 21882306
TI  - Nanoscale phase segregation of mixed thiolates on gold nanoparticles.

PMID- 21882308
TI  - Systems-based analysis of modified tRNA bases.

PMID- 21882309
TI  - Construction of substituted benzene rings by palladium-catalyzed direct cross
      coupling of olefins: a rapid synthetic route to 1,4-naphthoquinone and its
      derivatives.
AB  - Ring the changes: the direct cross-coupling of electron-deficient 1,4
      benzoquinone or its derivatives with electron-rich alkyl vinyl ethers proceeds in
      a tandem manner to produce substituted benzene rings with good selectivity and in
      good to excellent yields. The reaction has the potential for the rapid synthesis
      of diverse substituted benzene rings as it is not limited by substituent effects.

PMID- 21882310
TI  - Impairments in multisensory processing are not universal to the autism spectrum:
      no evidence for crossmodal priming deficits in Asperger syndrome.
AB  - Individuals suffering from autism spectrum disorders (ASD) often show a tendency
      for detail- or feature-based perception (also referred to as "local processing
      bias") instead of more holistic stimulus processing typical for unaffected
      people. This local processing bias has been demonstrated for the visual and
      auditory domains and there is evidence that multisensory processing may also be
      affected in ASD. Most multisensory processing paradigms used social-communicative
      stimuli, such as human speech or faces, probing the processing of simultaneously
      occuring sensory signals. Multisensory processing, however, is not limited to
      simultaneous stimulation. In this study, we investigated whether multisensory
      processing deficits in ASD persist when semantically complex but nonsocial
      stimuli are presented in succession. Fifteen adult individuals with Asperger
      syndrome and 15 control persons participated in a visual-audio priming task,
      which required the classification of sounds that were either primed by
      semantically congruent or incongruent preceding pictures of objects. As expected,
      performance on congruent trials was faster and more accurate compared with
      incongruent trials (crossmodal priming effect). The Asperger group, however, did
      not differ significantly from the control group. Our results do not support a
      general multisensory processing deficit, which is universal to the entire autism
      spectrum.

PMID- 21882311
TI  - Rapid, simple, and high-throughput antimicrobial susceptibility testing and
      antibiotics screening.

PMID- 21882312
TI  - Adjustable electrophilicity by cooperative hydrogen bonds.

PMID- 21882313
TI  - Rapid photoassisted access to N,O,S-polyheterocycles with benzoazocine and
      hydroquinoline cores: intramolecular cycloadditions of photogenerated
      azaxylylenes.

PMID- 21882314
TI  - Cobalt-catalyzed 1,4-hydrobutadienylation of 1-aryl-1,3-dienes with 2,3-dimethyl
      1,3-butadiene.

PMID- 21882315
TI  - Asymmetric allylic monofluoromethylation and methylation of Morita-Baylis-Hillman
      carbonates with FBSM and BSM by cooperative cinchona alkaloid/FeCl2 catalysis.

PMID- 21882316
TI  - Simple proton spectra from complex spin systems: pure shift NMR spectroscopy
      using BIRD.

PMID- 21882317
TI  - Advances with ammonia-borane: improved recycling and use as a precursor to
      atomically thin BN films.

PMID- 21882318
TI  - A highly enantioselective Overman rearrangement through asymmetric counteranion
      directed palladium catalysis.

PMID- 21882319
TI  - Synthesis of 1-aza-2-borabutatriene rhodium complexes by thermal borylene
      transfer from [(OC)5Mo=BN(SiMe3)2].

PMID- 21882320
TI  - Proline-based P,O ligand/iridium complexes as highly selective catalysts:
      asymmetric hydrogenation of trisubstituted alkenes.

PMID- 21882321
TI  - Tuning chemoselectivity in iron-catalyzed Sonogashira-type reactions using a
      bisphosphine ligand with peripheral steric bulk: selective alkynylation of
      nonactivated alkyl halides.

PMID- 21882322
TI  - Hydrogenation of CO at a uranium(III) center.

PMID- 21882323
TI  - Aromatic metal-centered monocyclic boron rings: Co(c)B8- and Ru(c)B9-.

PMID- 21882325
TI  - Direct asymmetric alpha benzoyloxylation of cyclic ketones.

PMID- 21882326
TI  - Aromatic ylide-stabilized carbocyclic silylene.

PMID- 21882324
TI  - A fluorescent probe for fast and quantitative detection of hydrogen sulfide in
      blood.

PMID- 21882327
TI  - Capture of carbon dioxide at the gas-liquid interface elucidated by surface
      science approaches.

PMID- 21882328
TI  - Theoretical chemistry--quo vadis?

PMID- 21882331
TI  - New insight into marine alkaloid metabolic pathways: revisiting oroidin
      biosynthesis.
AB  - Sponge natural product biosynthesis: A highly sensitive in vivo protocol based on
      (14)C radiolabeled precursors and beta-imager autoradiography allowed the
      unraveling of the origin of the pyrrole 2-aminoimidazole-containing key
      biosynthetic intermediate oroidin. Proline and lysine are now proposed as the
      early precursors of the pyrrole and the 2-aminoimidazole moieties of oroidin
      respectively.

PMID- 21882332
TI  - Ultrafast photochemistry of dithizonatophenylmercury(II).
AB  - The initial photochromic reaction of dithizonatophenylmercury(II) in solution was
      investigated by femtosecond transient absorption spectroscopy. Ultrafast
      excitation within less than 100 fs caused a radiationless photoreaction with a
      time constant of 1.5 ps, which is interpreted as C=N isomerization through a
      conical intersection. The orthogonally twisted intermediate state was observed
      through its excited-state absorption. Bifurcation along pathways towards the
      ground states of the orange cis and blue trans configurations occurs below the
      funnel of the conical intersection. The photochromism of the title compound in a
      very polar solvent such as methanol is observed for the first time.

PMID- 21882333
TI  - Comparative study of CeO2 and doped CeO2 with tailored oxygen vacancies for CO
      oxidation.
AB  - We report on the preparation and characterization of CeO(2) nanofibers (CeO(2)
      NFs) and nanocubes (CeO(2)-NCs), as well as Sm- and Gd-doped CeO(2) nanocubes (Sm
      CeO(2)-NCs and Gd-CeO(2)-NCs), synthesized by a simple hydrothermal process for
      CO catalytic oxidation. The samples were characterized by X-ray diffraction
      (XRD), Brunauer-Emmett-Teller (BET), X-ray photoelectron spectroscopy (XPS),
      transmission electron microscopy (TEM), Raman spectroscopy, and photoluminescence
      spectroscopy. Their oxygen-storing capacity (OSC) was examined by means of
      hydrogen temperature-programmed reduction (H(2)-TPR) and oxygen pulse techniques.
      Their catalytic properties for CO catalytic oxidation were comparatively
      investigated. The results showed that the CeO(2)-NFs possessed a higher catalytic
      activity compared to the CeO(2)-NCs because of their smaller size and the greater
      number of oxygen vacancies. The activity of the Sm-CeO(2)-NCs was higher than
      that of the CeO(2)-NCs due to an increase in the number of oxygen vacancies,
      which results from the substitution of Ce(4+) species with Sm(3+) ions. In
      contrast, Gd doping had a negative effect on the CO catalytic oxidation due to
      the special electron configuration of Gd(3+) (4f(7)). Our work demonstrates that
      the oxygen vacancies in pure CeO(2) and the electron configuration of the dopants
      in doped CeO(2) play an important role in CO oxidation.

PMID- 21882335
TI  - Influence of electron doping on the hydrogenation of fullerene C60 : a
      theoretical investigation.
AB  - The influence of electron attachment on the stability of the mono- and
      dihydrogenated buckminsterfullerene C(60) was studied using density functional
      theory and semiempirical molecular orbital techniques. We have also assessed the
      reliability of computationally accessible methods that are important for
      investigating the reactivity of graphenic species and surfaces in general. The
      B3LYP and M06L functionals with the 6-311+G(d,p) basis set and MNDO/c are found
      to be the best methods for describing the electron affinities of C(60) and
      C(60)H(2) . It is shown that simple frontier molecular orbital analyses at both
      the AM1 and B3LYP/6-31G(d) levels are useful for predicting the most favourable
      position of protonation of C(60)H(-) , that is, formation of the kinetically
      controlled product 1,9-dihydro[60]fullerene, which is also the thermodynamically
      controlled product, in agreement with experimental and previous theoretical
      studies. We have shown that reduction of exo- and endo-C(60)H makes them more
      stable in contrast to the reduction of the exo,exo-1,9-C(60)H(2) , reduced forms
      of which decompose more readily, in agreement with experimental electrochemical
      studies. However, most other dihydro[60]fullerenes are stabilized by reduction
      and the regioselectivity of addition is predicted to decrease as the less stable
      isomers are stabilized more by the addition of electrons than the two most stable
      ones (1,9 and 1,7).

PMID- 21882334
TI  - Long-lived states to monitor protein unfolding by proton NMR.
AB  - The relaxation of long-lived states (LLS) corresponds to the slow return to
      statistical thermal equilibrium between symmetric and antisymmetric proton spin
      states. This process is remarkably sensitive to the presence of external spins
      and can be used to obtain information about partial unfolding of proteins. We
      detected the appearance of a destabilized conformer of ubiquitin when urea is
      added to the protein in its native state. This conformer shows increased mobility
      in the C-terminus, which significantly extends the lifetimes of proton LLS
      magnetisation in Ser-65. These changes could not be detected by conventional
      measurements of T(1) and T(2) relaxation times of protons, and would hardly be
      sensed by carbon-13 or nitrogen-15 relaxation measurements. Conformers with
      similar dynamic and structural features, as revealed by LLS relaxation times,
      could be observed, in the absence of urea, in two ubiquitin mutants, L67S and
      L69S.

PMID- 21882336
TI  - The plasmonic ruler goes 3D!

PMID- 21882337
TI  - The fluorescence of Mg-Al-Eu ternary layered hydroxides response to tryptophan.
AB  - We have studied the fluorescence of Mg-Al-Eu ternary layered hydroxides (TLH)
      quenched by tryptophan (Trp). IR spectroscopy was used to evaluate the change of
      Trp structure which was caused by TLH. XRD and TG-DTA results further suggested a
      structural change of Trp after being reacted with TLH. XPS characterization
      confirmed a strong chemical reaction between Trp and TLH. These studies may
      present more direct evidence to explain the interrelation between the structural
      change of Trp and the fluorescent quenching of TLH.

PMID- 21882338
TI  - A novel chemiluminescence system for the determination of daidzein and its
      hydroxyl radical-scavenging capacity.
AB  - A novel chemiluminescence (CL) system was established for the determinations of
      daidzein in pharmaceutical preparations and to assess its ability to scavenge
      hydroxyl radicals. It was shown that a strong CL signal generated when eosin Y
      was mixed with Fenton reagent was decreased significantly when daidzein was added
      to the reaction system due to partial scavenging of the hydroxyl radicals in the
      solution. The extent of decrease in the CL intensity had a good stoichiometric
      relationship with the daidzein concentration. Based on this, we developed a new
      method for the determination of daidzein, using a flow-injection
      chemiluminescence (FI-CL) technique. Under the optimal conditions, the linear
      range of daidzein concentration was 8.0 * 10(-8) -3.0 * 10(-6)  mol/L (R =
      0.9982), with a detection limit of 9.0 * 10(-9)  mol/L (S:N = 3), and the RSD was
      5.8% for 1.0 * 10(-6)  mol/L daidzein (n = 11). This method was successfully used
      in the determination of daidzein in tablets and for evaluation of the hydroxyl
      radical-scavenging capacity of daidzein. The possible reaction mechanism of the
      CL system is discussed.

PMID- 21882339
TI  - What should be said to the lay public regarding ADHD etiology based on unbiased
      systematic quantitative empirical evidence.

PMID- 21882340
TI  - What should be said to the lay public regarding ADHD etiology.

PMID- 21882341
TI  - Novel approach to inhibiting chemokine function.

PMID- 21882342
TI  - Hepcidin and iron-mediated resistance to malaria.

PMID- 21882343
TI  - Silencing of microRNA-21 in vivo ameliorates autoimmune splenomegaly in lupus
      mice.
AB  - MicroRNAs (miRNAs) have been implicated in B cell lineage commitment, regulation
      of T cell differentiation, TCR signalling, regulation of IFN signalling, and
      numerous other immunological processes. However, their function in autoimmunity,
      and specifically in systemic lupus erythematosus (SLE), remains poorly
      understood. B6.Sle123 is a spontaneous genetic mouse model of SLE characterized
      by autoantibody production, lymphosplenomegaly, and glomerulonephritis. We
      identified several differentially regulated miRNAs in B and T lymphocytes of
      B6.Sle123 mice. We found that miR-21 expression in lupus B and T cells is up
      regulated and that in vivo silencing of miR-21 using a tiny seed-targeting LNA
      reversed splenomegaly, one of the cardinal manifestations of autoimmunity in
      B6.Sle123 mice, and de-repressed PDCD4 expression in vivo and in vitro. In
      addition, treatment with anti-miR-21 altered CD4/CD8 T cell ratios and reduced
      Fas receptor-expressing lymphocyte populations. Our study shows that tiny LNAs
      can be used to efficiently antagonize endogenous miRNAs in peripheral lymphocytes
      in vivo and in primary lymphocytes cultured ex vivo and can alter the course of a
      spontaneous genetic disease in mice.

PMID- 21882344
TI  - Neurodegeneration and functional impairments associated with glycogen synthase
      accumulation in a mouse model of Lafora disease.
AB  - Lafora disease (LD) is caused by mutations in either the laforin or malin gene.
      The hallmark of the disease is the accumulation of polyglucosan inclusions called
      Lafora Bodies (LBs). Malin knockout (KO) mice present polyglucosan accumulations
      in several brain areas, as do patients of LD. These structures are abundant in
      the cerebellum and hippocampus. Here, we report a large increase in glycogen
      synthase (GS) in these mice, in which the enzyme accumulates in LBs. Our study
      focused on the hippocampus where, under physiological conditions, astrocytes and
      parvalbumin-positive (PV(+)) interneurons expressed GS and malin. Although LBs
      have been described only in neurons, we found this polyglucosan accumulation in
      the astrocytes of the KO mice. They also had LBs in the soma and some processes
      of PV(+) interneurons. This phenomenon was accompanied by the progressive loss of
      these neuronal cells and, importantly, neurophysiological alterations potentially
      related to impairment of hippocampal function. Our results emphasize the
      relevance of the laforin-malin complex in the control of glycogen metabolism and
      highlight altered glycogen accumulation as a key contributor to neurodegeneration
      in LD.

PMID- 21882347
TI  - Meeting report: 24th International symposium, exhibit and workshops on
      preparative and process chromatography - PREP2011.

PMID- 21882345
TI  - RNA dynamics: perspectives from spin labels.
AB  - Dynamics are important and indispensible physical attributes that play essential
      roles in RNA function. RNA dynamics are complex, spanning vast timescales, and
      encompassing a large number of physical modes. The technique of site-directed
      spin labeling (SDSL), which derives information on local structural and dynamic
      features of a macromolecule by monitoring a chemically stable nitroxide radical
      using electron paramagnetic resonance spectroscopy, has been applied to monitor
      intrinsic dynamics at defined structural states as well as to probe
      conformational transition dynamics of RNAs. The current state of SDSL studies of
      RNA dynamics is summarized here. Further development and application of SDSL
      promise to open up many more opportunities for probing RNA dynamics and
      connecting dynamics to structure and function.

PMID- 21882349
TI  - Z-DNA recognition in B-Z-B sequences by a cationic zinc porphyrin.
AB  - For the first time it has been shown by spectroscopic studies such as circular
      dichroism and UV/Vis that cationic zinc porphyrin serves as a selective
      spectroscopic sensor that is able to recognize short left-handed Z-DNA tracts
      embedded in the B-Z-B sequences.

PMID- 21882348
TI  - Hydrophobic oxime ethers: a versatile class of pDNA and siRNA transfection
      lipids.
AB  - The manipulation of the cationic lipid structures to increase polynucleotide
      binding and delivery properties, while also minimizing associated cytotoxicity,
      has been a principal strategy for developing next-generation transfection agents.
      The polar (DNA binding) and hydrophobic domains of transfection lipids have been
      extensively studied; however, the linking domain comprising the substructure used
      to tether the polar and hydrophobic domains has attracted considerably less
      attention as an optimization variable. Here, we examine the use of an oxime ether
      as the linking domain. Hydrophobic oxime ethers were readily assembled via click
      chemistry by oximation of hydrophobic aldehydes using an aminooxy salt. A facile
      ligation reaction delivered the desired compounds with hydrophobic domain
      asymmetry. Using the MCF-7 breast cancer, H1792 lung cancer and PAR C10 salivary
      epithelial cell lines, our findings show that lipoplexes derived from oxime ether
      lipids transfect in the presence of serum at higher levels than commonly used
      liposome formulations, based on both luciferase and green fluorescent protein
      (GFP) assays. Given the biological compatibility of oxime ethers and their ease
      of formation, this functional group should find significant application as a
      linking domain in future designs of transfection vectors.

PMID- 21882350
TI  - Metal-free 1,5-regioselective azide-alkyne [3+2]-cycloaddition.
AB  - [3+2]-cycloaddition reactions of aromatic azides and silylated alkynes in aqueous
      media yield 1,5-disubstituted-4-(trimethyl-silyl)-1H-1,2,3-triazoles. The
      formation of the 1,5-isomer is highly favored in this metal-free cycloaddition,
      which could be proven by 1D selective NOESY and X-ray investigations.
      Additionally, DFT calculations corroborate the outstanding favoritism regarding
      the 1,5-isomer. The described method provides a simple alternative protocol to
      metal-catalyzed "click chemistry" procedures, widening the scope for
      regioselective heavy-metal-free synthetic applications.

PMID- 21882351
TI  - 10 years of click chemistry: synthesis and applications of ferrocene-derived
      triazoles.
AB  - Click chemistry has played a significant role as a rapid and versatile strategy
      for conjugating two molecular fragments under very mild reaction conditions.
      Introduction of ferrocene-derived triazole systems using click chemistry has
      attracted enormous interest in various fields due to its potential applications
      in electrochemical techniques for detection and sensing. The present discussion
      focuses on the synthesis of ferrocene-triazole and the importance of using a
      CuAAC reaction for such conjugation. Applications of ferrocene-based click
      reactions in conjugate chemistry, asymmetric catalysis, medicinal chemistry, host
      guest interactions, and materials chemistry have been highlighted.

PMID- 21882352
TI  - Imaging the reaction dynamics of O(3P)+CH4->OH+CH3.
AB  - The title reaction was studied in a crossed-beam experiment, in which the ground
      state methyl products were probed using a time-sliced velocity-imaging technique.
      By taking images over the energy range of chemical significance, from the
      threshold to about 15 kcal mol(-1), the reactive excitation function as well as
      the dependences of product angular distributions and of the energy disposal on
      initial collision energies were determined. All experimental data are consistent
      with the picture that the ground-state reaction of O((3)P)+CH(4) proceeds via a
      direct abstraction rebound-type mechanism with a narrow cone of acceptance.
      Deeper insights into the underlying mechanism and the key feature of the
      potential-energy surface are elucidated by comparing the results with the
      corresponding observables in the analogous Cl+CH(4) reaction.

PMID- 21882353
TI  - Plume expansion dynamics of matrix-assisted laser desorption ionization.
AB  - High-resolution angular and velocity distributions for neutral analytes
      (tryptophan and poly-tryptophan) and matrix (2,4,6-trihydroxyacetophenon, THAP)
      are measured by using 355 nm laser desorption. The information suggests that two
      separate mechanisms dominate the angular and velocity distributions at the
      beginning and before the end of desorption. A molecular jet-like isentropic
      expansion dominates the plume expansion at the beginning of desorption. This only
      occurs at high surface temperature, thus resulting in a large velocity normal to
      the surface and a very narrow angular distribution. Most of the analytes are
      produced under these conditions. Before the end of desorption, the surface
      temperature decreases and the mechanism of thermal desorption at low vapor
      pressure takes over. The velocities become small and the angular distribution is
      close to costheta. Only a very small amount of analytes are generated under these
      conditions. Compared to tryptophan, poly-tryptophan has a much narrower angular
      distribution, thereby suggesting that it is only produced at the higher surface
      temperatures.

PMID- 21882354
TI  - Metal-crossing between thiolato-bridged tetragold(I) and tetrasilver(I)
      metallorings.

PMID- 21882355
TI  - Solvent-free, microwave-assisted N-arylation of indolines by using low palladium
      catalyst loadings.
AB  - Indoline-based compounds are abundant in nature, and the indoline skeleton is an
      often-encountered scaffold in a range of biologically active alkaloids,
      pharmaceutically active compounds, and functional molecules (e.g., sensitizers
      for solar cells). The wide range of uses warrants further interest in the
      structural modification of this class of compounds. A series of substituted N
      aryl indolines is prepared by a solvent-free, palladium-catalyzed procedure. The
      procedure requires only low loadings of catalyst, uses microwave irradiation, and
      starts from commercially available substrates. The method proceeds in good yields
      and in short reaction times with aryl bromides, chlorides, and iodides, also on 2
      substituted indolines. The combination of solvent-free methods with microwave
      heating will further increase in importance in the search for more
      environmentally acceptable synthesis methods.

PMID- 21882356
TI  - EGFR mutation testing in nonsmall cell lung cancer patients by using cytology
      specimens: when the tissue is no longer the issue.

PMID- 21882357
TI  - On-site adequacy evaluations performed by cytotechnologists: correlation with
      final interpretations of 5241 image-guided fine-needle aspiration biopsies.
AB  - BACKGROUND: Practice patterns regarding on-site assessment of the adequacy of
      image-guided fine-needle aspiration biopsies (FNABs) vary among laboratories, but
      in many laboratories primary responsibility rests with the cytotechnologists. On
      site evaluation provides feedback on the need for additional passes and
      facilitates triaging of the specimen for time-sensitive ancillary studies. Prior
      studies have suggested that cytotechnologists can assess the initially obtained
      specimens correctly, but they are few in number and limited by small size. The
      purpose of this study was to assess the frequency with which our
      cytotechnologists were able to correctly assess specimens as adequate using a
      large-scale database that included a wide range of image-guided FNABs. METHODS:
      The frequency that on-site adequacy assessments of 5241 image-guided FNABs were
      correct was determined by correlating the cytotechnologists' assessments of
      adequacy with the final cytologic interpretation. An adequacy assessment was
      considered correct if the FNAB was ultimately reported as satisfactory and
      unequivocally benign or malignant. An adequate reading on a case that was
      ultimately reported as unsatisfactory, atypical, or suspicious was deemed
      "incorrect." The effect of imaging modality was also analyzed. RESULTS: Of 5241
      FNABs, 2784 (53%) were interpreted as adequate on site. Of these, 2637 (95%) were
      correctly considered adequate. Of the common biopsy sites sampled, the adequacy
      assessments for liver FNABs demonstrated the highest frequency for being
      correctly considered adequate (97%) and those for kidney FNABs showed the lowest
      (90%). Imaging modality had no effect on accuracy. CONCLUSIONS: Cytotechnologists
      are almost always correct when assessing initial FNAB samples as adequate.

PMID- 21882358
TI  - Cytologic and molecular diagnosis of thyroid cancers: is it time for routine
      reflex testing?
AB  - The Bethesda system for standardized reporting of thyroid fine needle aspiration
      (FNA) cytology has positively affected the clarity of communication of results
      and management of patients evaluated for thyroid nodules. Problematic areas still
      exist in the triage of some of these samples, particularly those in the
      categories of "follicular lesion with atypia of uncertain significance" and
      "follicular lesion." The literature on molecular and genetic abnormalities in
      thyroid lesions is reviewed. Potentially useful markers for distinguishing
      currently problematic categories of FNA cytologic samples, especially
      nondiagnostic samples, atypia of uncertain significance, and follicular lesions,
      are discussed. The predictive value of the respective molecular analyses in these
      settings is examined. Evaluation of FNA samples with negative or suboptimal
      follicular cytology for Ras mutations may be useful in detecting potentially
      significant follicular lesions (carcinomas) but is quite low in overall yield.
      Cytologic samples with atypia of uncertain significance, which may include the
      possibility of papillary carcinomas, may be fruitfully evaluated using a panel of
      molecular tests for BRAF, RET/PTC, PAX8/PPARG1, and Ras. Other markers also have
      potential utility in the workup of thyroid lesions. An era of combined modality
      testing in thyroid cytology is emerging in which classical cytologic findings can
      be coupled with molecular data to increase the predictive power of diagnostic
      interpretations; however, there remains a group of atypical cytologic samples
      negative for known molecular markers in which the risk of malignancy is too high
      to simply follow expectantly.

PMID- 21882359
TI  - Factor analysis of the Parenting Stress Index-Short Form with parents of young
      children with autism spectrum disorders.
AB  - The primary purpose of this study was to examine the underlying factor structure
      of the Parenting Stress Index-Short Form (PSI-SF) in a large cohort of parents of
      young children with autism spectrum disorder (ASD). A secondary goal was to
      examine relationships between PSI-SF factors and autism severity, child behavior
      problems, and parental mental health variables that have been shown to be related
      to parental stress in previous research. A confirmatory factor analysis (CFA) was
      used to examine the three-factor structure described in the PSI-SF manual
      [Abidin, 1995]: parental distress, parent-child dysfunctional interaction, and
      difficult child. Results of the CFA indicated that the three-factor structure was
      unacceptable when applied to the study sample. Thus, an exploratory factor
      analysis was conducted and suggested a six-factor model as the best alternative
      for the PSI-SF index. Spearman's correlations revealed significant positive
      correlations with moderate to large effect sizes between the revised PSI-SF
      factors and autism severity, externalizing and internalizing child behaviors, and
      an index of parent mental health. The revised factors represent more narrowly
      defined aspects of the three original subscales of the PSI-SF and might prove to
      be advantageous in both research and clinical applications. Autism Res 2011,4:336
      346. (c) 2011 International Society for Autism Research, Wiley Periodicals, Inc.

PMID- 21882360
TI  - Brain abnormalities in a Neuroligin3 R451C knockin mouse model associated with
      autism.
AB  - Magnetic resonance imaging (MRI) has been used quite extensively for examining
      morphological changes in human and animal brains. One of the many advantages to
      examining mouse models of human autism is that we are able to examine single gene
      targets, like that of Neuroligin3 R451C knockin (NL3 KI), which has been directly
      implicated in human autism. The NL3 KI mouse model has marked volume differences
      in many different structures in the brain: gray matter structures, such as the
      hippocampus, the striatum, and the thalamus, were all found to be smaller in the
      NL3 KI. Further, many white matter structures were found to be significantly
      smaller, such as the cerebral peduncle, corpus callosum, fornix/fimbria, and
      internal capsule. Fractional anisotropy measurements in these structures were
      also measured, and no differences were found. The volume changes in the white
      matter regions, therefore, are not due to a general breakdown in the
      microstructure of the tissue and seem to be caused by fewer axons or less mature
      axons. A larger radial diffusivity was also found in localized regions of the
      corpus callosum and cerebellum. The corpus callosal changes are particularly
      interesting as the thinning (or reduced volume) of the corpus callosum is a
      consistent finding in autism. This suggests that the NL3 KI model may be useful
      for examining white matter changes associated with autism.

PMID- 21882362
TI  - What is the impact of autism on mother-child interactions within families with a
      child with autism spectrum disorder?
AB  - This within-family study investigated whether mothers differentiate between
      children in their interactive behavior. Mothers were observed during a play and a
      task interaction separately with their child with autism spectrum disorder (ASD)
      (between 46 and 84 months old, M = 68) and with a younger sibling (between 29 and
      67 months old, M = 48). Additionally, the social behavior of the children with
      ASD and their non-ASD siblings was compared. Results show that mothers
      differentiated in their responsiveness but not in their initiatives toward the
      children. Children with ASD and their non-ASD siblings were equally responsive
      but children with ASD were more imperative toward their caregiver. Several
      interpretations of these findings are discussed. Finally, it is concluded that
      family-based interventions will benefit from a better understanding of the effect
      of ASD on mother-child interactions within families with a child with ASD.
      Therefore, between-family studies should be complemented with within-family
      studies. Autism Res 2011,4:358-367. (c) 2011 International Society for Autism
      Research, Wiley Periodicals, Inc.

PMID- 21882363
TI  - Genetically inbred Balb/c mice differ from outbred Swiss Webster mice on discrete
      measures of sociability: relevance to a genetic mouse model of autism spectrum
      disorders.
AB  - The Balb/c mouse is proposed as a model of human disorders with prominent
      deficits of sociability, such as autism spectrum disorders (ASDs) that may
      involve pathophysiological disruption of NMDA receptor-mediated
      neurotransmission. A standard procedure was used to measure sociability in 8-week
      old male genetically inbred Balb/c and outbred Swiss Webster mice. Moreover,
      because impaired sociability may influence the social behavior of stimulus mice,
      we also measured the proportion of total episodes of social approach made by the
      stimulus mouse while test and stimulus mice were allowed to interact freely.
      Three raters with good inter-rater agreement evaluated operationally defined
      measures of sociability chosen because of their descriptive similarity to
      deficits of social behavior reported in persons with ASDs. The data support
      previous reports that the Balb/c mouse is a genetic mouse model of impaired
      sociability. The data also show that the behavior of the social stimulus mouse is
      influenced by the impaired sociability of the Balb/c strain. Interestingly,
      operationally defined measures of sociability did not necessarily correlate with
      each other within mouse strain and the profile of correlated measures differed
      between strains. Finally, "stereotypic" behaviors (i.e. rearing, grooming and
      wall climbing) recorded during the session of free interaction between the test
      and social stimulus mice were more intensely displayed by Swiss Webster than
      Balb/c mice, suggesting that the domains of sociability and "restricted
      repetitive and stereotyped patterns of behavior" are independent of each other in
      the Balb/c strain.

PMID- 21882361
TI  - The autism diagnosis in translation: shared affect in children and mouse models
      of ASD.
AB  - In the absence of molecular biomarkers that can be used to diagnose ASD, current
      diagnostic tools depend upon clinical assessments of behavior. Research efforts
      with human subjects have successfully utilized standardized diagnostic
      instruments, which include clinician interviews with parents and direct
      observation of the children themselves [Risi et al., 2006]. However, because
      clinical instruments are semi-structured and rely heavily on dynamic social
      processes and clinical skill, scores from these measures do not necessarily lend
      themselves directly to experimental investigations into the causes of ASD.
      Studies of the neurobiology of autism require experimental animal models. Mice
      are particularly useful for elucidating genetic and toxicological contributions
      to impairments in social function [Halladay et al., 2009]. Behavioral tests have
      been developed that are relevant to autism [Crawley, 2004, 2007], including
      measures of repetitive behaviors [Lewis, Tanimura, Lee, & Bodfish, 2007; Moy et
      al., 2008], social behavior [Brodkin, 2007; Lijam et al., 1997; Moretti,
      Bouwknecht, Teague, Paylor, & Zoghbi, 2005], and vocal communication [D'Amato et
      al., 2005; Panksepp et al., 2007; Scattoni et al., 2008]. Advances also include
      development of high-throughput measures of mouse sociability that can be used to
      reliably compare inbred mouse strains [Moy et al., 2008; Nadler et al., 2004], as
      well as measures of social reward [Panksepp & Lahvis, 2007] and empathy [Chen,
      Panksepp, & Lahvis, 2009; Langford et al., 2006]. With continued generation of
      mouse gene-targeted mice that are directly relevant to genetic linkages in ASD,
      there remains an urgent need to utilize a full suite of mouse behavioral tests
      that allows for a comprehensive assessment of the spectrum of social difficulties
      relevant to ASD. Using impairments in shared affect as an example, this paper
      explores potential avenues for collaboration between clinical and basic
      scientists, within an amply considered translational framework.

PMID- 21882364
TI  - Are thyroid hormone concentrations at birth associated with subsequent autism
      diagnosis?
AB  - Thyroid hormones substantially influence central nervous system development
      during gestation. We hypothesized that perturbations of early thyroid profiles
      may contribute to the development of autism spectrum disorders (ASD). Thyroid
      pathways could provide a mechanism by which environmental factors that affect the
      thyroid system may impact autism occurrence or phenotypic expression. We
      investigated whether thyroxine (T4) levels at birth are associated with
      subsequent ASD, using two existing California study groups in multivariate
      analysis. One study group included children born in the San Francisco Bay Area in
      1994, with cases identified through the California Department of Developmental
      Services (DDS) and/or the Kaiser Permanente Medical Care Program of Northern
      California (244 cases, 266 controls); the other included children born in
      California in 1995, with cases identified through DDS (310 cases, 518 controls).
      Matched controls were selected from birth certificate records. This exploratory
      analysis suggested that infants with very low T4 (<3rd percentile) may have
      higher ASD risk, although results reached statistical significance only for the
      1995 study group (1995: OR = 2.74 (95% CI 1.30-5.75; 1994: OR = 1.71 (95% CI 0.57
      5.19). A variety of alternate analyses were conducted with available data,
      without further resolution of the difference between the two study groups. The
      results of our study indicate that further studies are warranted to investigate
      whether thyroid hormone perturbations play a role in the development of ASD by
      evaluating additional potential confounders and genotype or phenotype in larger
      studies.

PMID- 21882366
TI  - Something in the air.

PMID- 21882365
TI  - Impact of gene vector design on the control of recombinant monoclonal antibody
      production by Chinese hamster ovary cells.
AB  - In this study, we systematically compare two vector design strategies for
      recombinant monoclonal antibody (Mab) synthesis by Chinese hamster ovary (CHO)
      cells; a dual open reading frame (ORF) expression vector utilizing separate
      cytomegalovirus (CMV) promoters to drive heavy chain (HC) and light chain (LC)
      expression independently, and a single ORF vector design employing a single CMV
      promoter to drive HC and LC polypeptide expression joined by a foot and mouth
      disease virus F2A polypeptide self-cleaving linker sequence. Initial analysis of
      stable transfectants showed that transfectants utilizing the single ORF vector
      designs exhibited significantly reduced Mab production. We employed an empirical
      modeling strategy to quantitatively describe the cellular constraints on
      recombinant Mab synthesis in all stable transfectants. In all transfectants, an
      intracellular molar excess of LC polypeptide over HC polypeptide was observed.
      For CHO cells transfected with the single ORF vectors, model-predicted, and
      empirical intracellular intermediate levels could only be reconciled by inclusion
      of nascent HC polypeptide degradation. Whilst a local sensitivity analysis showed
      that qMab of all transfectants was primarily constrained by recombinant mRNA
      translation rate, our data indicated that all single ORF transfectants exhibited
      a reduced level of recombinant gene transcription and that Mab folding and
      assembly reactions generically exerted greater control over qMab. We infer that
      the productivity of single ORF transfectants is limited by ER
      processing/degradation "capacity" which sets a limit on transcriptional input. We
      conclude that gene vector design for oligomeric recombinant proteins should be
      based on an understanding of protein-specific synthetic kinetics rather than
      polypeptide stoichiometry.

PMID- 21882367
TI  - Conference speaker's allegory  found offensive.

PMID- 21882368
TI  - Protecting horses at the track.

PMID- 21882369
TI  - Low serum bilirubin concentrations are associated with impaired aortic elastic
      properties, but not impaired left ventricular diastolic function.
AB  - Elevated serum bilirubin concentrations protect from atherosclerotic diseases;
      however,it is not clear whether higher serum bilirubin concentrations in
      physiological ranges do the same. To investigate the association of high and low
      serum bilirubin concentrations with left ventricular diastolic function and
      aortic elastic properties.We evaluated left ventricular diastolic function and
      aortic elastic properties of 42 healthy subjects with hypobilirubinemia (total
      bilirubin 0.40 +/- 0.08 mg / dl; mean age 37.0 +/- 3.9) and 40 healthy subjects
      with hyperbilirubinemia (total bilirubin 1.56 +/- 0.49 mg / dl; mean age 36.2 +/-
      6.0) using transthoracic second harmonic Doppler echocardiography. Age, gender,
      body mass index and coronary risk factors were similar between the groups, except
      high-sensitivity C-reactive protein (hsCRP).Left ventricular diastolic parameters
      were similar between the two groups. Aortic distensibility (AoD) was found to be
      significantly lower (11.1 +/- 3.9 vs. 13.2 +/- 4.9,p = 0.03) and aortic stiffness
      index (AoSI) (1.99 +/- 0.30 vs. 1.85 +/- 0.26,p = 0.02) and elastic modulus
      (AoEM) (2.06 +/- 0.83 vs. 1.73 +/- 0.68, p = 0.03;the low and high bilirubin
      groups, respectively) higher in the low bilirubin group.Serum total bilirubin
      concentration correlated with hsCRP levels, AoD, AoSI and AoEM. In conclusion,
      left ventricular systolic and diastolic functions were similar between hypo- and
      hyperbilirubinemic subjects, but aortic elastic properties were impaired in
      subjects with lower serum bilirubin concentrations.

PMID- 21882370
TI  - Retraction. Activation of peroxisome proliferator-activated receptor beta/delta
      (PPARbeta/delta) increases the expression of prostaglandin E2 receptor subtype
      EP4. The roles of phosphatidylinositol 3-kinase and CCAAT/enhancer-binding
      protein beta.

PMID- 21882371
TI  - Sepsis and multiorgan dysfunction. Weimar Sepsis Update 2011- Bridging the Gap.
      Abstracts of the 5th International Congress of the German Sepsis Society.
      September 7-11, 2011. Weimar, Germany.

PMID- 21882372
TI  - The government's changes will only delay the tough decisions.

PMID- 21882373
TI  - Major powers to be focused at centre.

PMID- 21882374
TI  - Commissioning. No deadline set for transferring powers and budgets. Fears raised
      of two-tier system.

PMID- 21882375
TI  - Private sector complains brakes have been put on competition too fiercely.

PMID- 21882376
TI  - Readmissions penalties could cost trusts 600m pounds.

PMID- 21882377
TI  - Why clinicians need to get fiscal.

PMID- 21882378
TI  - On learning from the past. Raid the past for golden nuggets.

PMID- 21882379
TI  - [Long-wavelength infrared imaging of the subcutaneous vascular bed].

PMID- 21882380
TI  - Appeals court blasts mandate. 11th circuit ruling sets up high court showdown.

PMID- 21882381
TI  - Strong performance. Healthcare executives reaped big rewards in 2010, with
      returning hospital CEOs seeing a 58.2% gain in compensation.
AB  - Healthcare CEOs saw their compensation slip relative to other industries but
      still earned big paydays last year. "2010 was a great year for corporate earnings
      and stock performance," says Steve Kaplan, left, a professor of finance and
      entrepreneurship. "Part of the reason for the increase in pay is that the CEOs
      delivered in 2010."

PMID- 21882382
TI  - A swing and a hit. Reimbursement cuts potentially 'toxic,' S&P says.

PMID- 21882383
TI  - Wait and see. Downgrade may affect some more than others.

PMID- 21882384
TI  - On their terms. Providers take own direction with ACOs.

PMID- 21882385
TI  - Move beyond denial. Providers must accept that cuts are coming in government
      healthcare programs.

PMID- 21882386
TI  - Unsatisfactory marks. Hospitals question use of HCAHPS in scoring for value-based
      purchasing.

PMID- 21882387
TI  - Feeling pinched. Hospitals, docs anxious as 'provider payment cuts are pretty
      easy to do'.
AB  - In the aftermath of the debt-ceiling battle, providers are feeling nervous since
      lawmakers need to come up with another $1.5 trillion in cuts by the end of the
      year. "Provider payment cuts are pretty easy to do, relatively speaking. And
      there doesn't seem to be a clear connection in the minds of policymakers that
      equates payment cuts with access problems," says Michael Regier, left, of
      provider alliance VHA.

PMID- 21882388
TI  - Payment boost. But future adjustments concern hospitals.

PMID- 21882389
TI  - Holding steady. Operating margins same, with overall increase.

PMID- 21882390
TI  - Going private again. Blackstone to buy Emdeon for $3 billion.

PMID- 21882392
TI  - Plan shake-up. Cuts to SNF reimbursement causes scramble.

PMID- 21882391
TI  - Cadillac tax revs worries. Employers look for ways to avoid excise tax.

PMID- 21882393
TI  - Head of the pack. Early EHR subsidy recipients may have experience.

PMID- 21882394
TI  - We must provide needed services. Challenge for government, healthcare: helping
      poor without going broke.

PMID- 21882395
TI  - It started with a palm pilot. Ingenious Med chief named Entrepreneur of the Year.

PMID- 21882397
TI  - Retraction. Fibronectin increases matrix metalloproteinase 9 expression through
      activation of c-Fos via extracellular-regulated kinase and phosphatidylinositol 3
      kinase pathways in human lung carcinoma cells.

PMID- 21882398
TI  - Abstracts of the 41st Annual European Society for Dermatological Research (ESDR)
      Meeting. September 7-10, 2011. Barcelona, Spain.

PMID- 21882396
TI  - ESC/EAS Guidelines for the management of dyslipidaemias The Task Force for the
      management of dyslipidaemias of the European Society of Cardiology (ESC) and the
      European Atherosclerosis Society (EAS).

PMID- 21882473
TI  - Reply: describing life to define death: a Cuban perspective.

PMID- 21882474
TI  - Education--the AAE takes it seriously.

PMID- 21882475
TI  - [Survival analysis and prognosis of lung cancer related factors].
AB  - AIM: of non-small cell lung cancer (non a small eelllungeaneer, NSCLC) patients
      with survival analysis and prognostic factors. METHODS: The research I our
      hospital from 2005 to September 2010 on the treatment of 275 cases of clinical
      data of patients with NSCLC, and its age, pathological type, clinical stage,
      lymph node micrometastasis on prognosis and treatment Investigation of influence,
      and to analyze the prognostic factors for patients. RESULTS: The patients in the
      family history, clinical stage and other factors after treatment for patients
      with poor prognostic factors after treatment for patients with poor prognostic
      factors for survival. The treatment of choice for the greatest impact factor.
      This group of patients selected surgery plus chemotherpy, chemotherapy +
      radiotherapy, chemotherapy and symptomatic treatment 4, in the survival rates of
      patients in the four groups was significantly different (P < 0.05). The patients
      age, clinical stage, lymph node micrometastasis in pathological type on the
      prognosis of patients was statistically significant. CONCLUSION: The treatment of
      non-small cell lung cancer is an important prognostic factor.

PMID- 21882476
TI  - [Correlation between TGF- beta1 expression and Treg cell infiltration in glioma].
AB  - AIM: To investigate correlation between the expression of TGF-beta1 and the
      amount of Treg cell in glioma, and evaluate their clinical values in predicting
      the prognosis of glioma. METHODS: Double immunohistochemistry staining was used
      to detect the expression of TGF-beta1, CD4 and Foxp3 in 135 specimens of human
      gliomas (WHO I 18, WHO II 45, WHO III 53, WHO IV 19) and 15 normal brain.
      RESULTS: OF the 135 specimans of glioma, 58 showed low TGF-beta1 expression and
      77 (57.03%) showed high TGF-beta1 expression while ws not expression in normal
      brain tissue. Average Treg cell density in glioma was 2. 031/HP, but there was no
      expression of Treg in normal brain tissue. Expression of TGF-beta1 was positively
      correlated with the mount of Treg in glioma tissues (r = 0.294, P < 0.01).
      Compared with the low grade, The levels of TGF-beta1 and the amount of Treg cells
      with significant higher in high-grade glioma, however the mount of Treg had no
      correlations with Sex, KPS score. The Laplan-Meier analysis showed that there wer
      significant difference in overall survival (OS) between the TGF-beta1 high
      expression and low-expression group (P < 0.001). Cox multivariate analysis showed
      that TGF-beta1 and Treg were not independent prognostic factors (P > 0.05).
      CONCLUSION: Intratumoral of TGF-beta1 may relate to the infiltration of Treg
      cells in glioma tissues. The level of TGF-beta1 was obviously increased in high
      grade. Glioma patients with TGF-beta1 or Trg high expression have poorer
      prognosis, while TGF-beta1 and Treg cannot serve as independent prognostic
      factors of glioma survival time.

PMID- 21882477
TI  - [Changes of MMP-9 and TIMP-1 levels in gingival crevicular fluid during
      orthodontic tooth movement under orthodontic forces].
AB  - AIM: To investigate the dynamic changes of MMP-9 and TIMP-1 levels in gingival
      crevicular fluid during orthodontic tooth movement under orthodontic forces.
      METHODS: select 20 cases which fit experiment condition. The cases divided
      randomly into 2 groups, 1- cases for each group. The distal forces of 100g and
      250 g were exerted to the canine on the one side of two groups separately. The
      GCF were taken before activation and at 1, 2, 3, 4, 5, 6, 7 week respectively
      after initiation of the experiment. The levels of MMP-9 and TIMP-1 in GCF were
      determined by ELISA. RESULTS: The levels of MMP-9 in A group began to increase at
      1 week and reached to its peak value at 3 week after initiation of the
      experiment, but the level returned to baseline at 7 week. The levels of TIMP-1 in
      A group began to increase at 1, 2, 3 week and decreased at 4 week after
      initiation of the experiment, but the level at 6,7 week was higher than that
      before initiation of the experiment. The level of MMP-9 in A group was higher
      than that in B group at all times and the level of TIMP-1 in A group was lower
      than that in B group. CONCLUSION: The level of MMP-9 and TIMP-1 in GCF may play
      an importance role in maintaining the health, the regular remodeling of the
      periodontium and the fast-moving of orthodontic tooth.

PMID- 21882478
TI  - Medical School Hotline: from Kaka'ako to Manila: lessons learned in global
      health.

PMID- 21882480
TI  - Persistent danger from weight loss supplements.

PMID- 21882479
TI  - UH Cancer Center Hotline: addressing cancer care disparities for Filipinos in
      Hawai'i; a unique approach to communicating about cancer treatment.

PMID- 21882481
TI  - [Effect of ciglitazone on THP-1 macrophage CD36 expression and cholesterol
      influx].
AB  - AIM: To investigate the effect of ciglitazone on CD36 expression and cholesterol
      influx in THP-1 macrophage. METHODS: After exposure of the cultured THP-1
      macrophage to ciglitazone for 24 h, [(3)H] labeled Cholesterol influx was
      determined by FJ-2107P typed liquid scintillator. CD36 mRNA and protein level
      were determined by reverse transcription-polymerase chain reaction (RT-PCR) and
      Western blotting respectively. RESULTS: PPARgamma agonist, ciglitazone, elevated
      CD36 in both protein and mRNA levels, and increased cholesterol influx in THP-1
      macrophage. The levels of cholesterol influx were 20. 3%, 28. 6%, 37. 2%, 44. 3%,
      48. 7% respectively. CONCLUSION: Our results indicated that ciglitazone may play
      an important role in cholesterol influx and modulating CD36 expression in THP-1
      macrophage.

PMID- 21882482
TI  - [Expression of IL-18, IL-6 and oxidative stress in rat peritoneal mesothelial
      cells stimulated by lipopolysaccharide].
AB  - AIM: To observe the expression of IL-18, IL-6 and the production of oxidative
      stress Malondialdehyde (MDA) in rat peritoneal mesothelial cells (RPMC)
      stimulated by lipopolysaccharide (LPS). METHODS: RPMC were primordially culture
      and stimulated with different concentrations (1, 10, 100 mg/L) LPS for 6h; RPMC
      were stimulated by 10 mg/L LPS for 3, 6, 12, 24 h. IL-18 mRNA was detected by
      real time-PCR. IL-6 and IL-18 were detected by ELISA in supernatants. MDA was
      measured by thiobarbiuric acid method. RESULTS: Compared with the control group,
      the expression of IL-18, IL-6 and MDA were gradually increased by LPS with
      different concentrations (P < 0.05) ; the expression of targets above were little
      by little increased with stimulated time prolonging. then the peak of IL-18 were
      appeared in 12 h. CONCLUSION: The expression of proinflammatory cytokine IL-6 and
      the production of oxidative stress MDA was increased in the RPMCs stimulated by
      LPS, then leads to the perpetuating amplificated inflammation, aggravate
      peritoneal impairment and hyperfiltration losed.

PMID- 21882483
TI  - [Establishment and primary application of sandwich ELISA method to detect
      tenascin-C].
AB  - AIM: To establish a sandwich method to detect tenascin-c on the basis of
      preparation of monoclonal antibodies (mAbs) against tenascin-C (TN-C). METHODS:
      The ascites of three stains of mAbs (No. 1A8, 3H7 and 4D6) were prepared and
      purified. The mAbs were conjugated with HRP and paired, respectively. The
      recombinant TN-C was taken as standard to analyze the optimal combination between
      mAbs. The sera TN-C concentrations of patients with osteosarocoma and the normal
      persons were evaluated with the sandwich ELISA method. RESULTS: Among these mAbs,
      the sensitivity was obtained when combined the coated 1A8 with HRP-4D6. The sera
      TN-C significantly higher than the normal controls. CONCLUSION: The sandwich
      ELISA method to detect TN-C was established successfully. The sera TN-C
      concentrations of patients with osteosarcoma and the normal persons were found
      distinct with the sandwich method.

PMID- 21882484
TI  - [Effects of different doses of nano silver on vascular endothelial cell
      proliferation in vitro].
AB  - AIM: To explore the effects of different doses of nano silver of proliferation of
      cultured vascular endothelial cells in vitro. METHODS: The hearts of three
      newborn SD rats 5 day old were mechanically minced the enzymatically digested
      with collagenase and trypsin, then vascular endothelial cell were counted, washed
      and resuspended in Dulbecco's minimumes sential medium (DMEM) added with 20% heat
      in activated fetal calf serum, then inoculated d in 2% gelatin coated tissue
      culture flasks. Vascular endothelial cells at passage 3 were used in the
      experiment. Except for the normal control group, the vascular endothelial cells
      were cultured with nano silver in various concentrations (0.5, 0.25, 0.125,
      0.0625, 0.03125 g/l) for 24 hours, and the morphology and the number of the
      cultured endothelial cells were observed. Methly thiazolyl tetrazolium (MTT)
      colorimetry was used to determine the proliferation of the cultured vascular
      endothelial cells. Flow cytometry (FCM) were used to detect the proliferation
      index (PI) of the vascular endothelial cells and the expressions of proliferating
      cell nuclear antigen (PCNA) was detected by immunohistochemical method. RESULTS:
      The cell morphology was normal under the inverted microscoped in each group. The
      number and proliferation activities of vascular endothelial cells were
      significantly decreased by 0.5, 0.25, 0.125, 0.0625, 0.03125 g/l nano silver
      compared with those of the blank control group, especially the 0.25 g/l nao
      silver group, and there were no remarkable changes in with 0.5 g/L, 0.125 g/L,
      0.0625 g/L and 0.03125 g/L nano silver groups compared to each other. The same
      results were seen in the positive rate of PCNA expression and PI. CONCLUSION:
      Nano silver has dose-dependent effects on the proliferation activity of vascular
      endothelial cells. It inhibited the proliferation of vascular endothelial cells.

PMID- 21882485
TI  - [Significance of topographic placement of incision during limited incision
      technique in carpal tunnel release].

PMID- 21882486
TI  - Idiopathic ventricular tachycardia originating from the posteroseptal mitral
      annulus: a case report.
AB  - Idiopathic VT originating from posteroseptal mitral annulus. We describe a 71
      year-old man with a ventricular tachycardia (VT) originating from the mitral
      annulus. A sustained VT was induced by exercise or an isoproterenol
      administration, but not by pacing. Frequent premature ventricular
      contractions(PVCs) with the same QRS as the VT were transiently suppressed by an
      adenosine triphosphate injection,suggesting that it was due to cyclic-AMP
      mediated triggered activity. The PVCs and VT were all abolished by radiofrequency
      catheter ablation guided by the earliest activation and a perfect pace map, which
      was located at the posteroseptal mitral annulus. The patient has been free from
      any symptoms for 2 years.(J Cardiovasc Electrophysiol, Vol. 17, pp. 1375-1377,
      December 2006)

PMID- 21882487
TI  - Real-world challenges of treating osteoporosis.
AB  - Numerous treatments have been shown to significantly reduce the risk of
      osteoporosis-related fracture. Treating patients with osteoporosis therapies
      after an initial osteoporotic fracture can reduce the risk of future fractures
      40% to 60%, resulting in significant cost reductions. But despite the
      availability of effective management strategies, osteoporosis management is still
      suboptimal. Barriers to providing quality care include knowledge, competency, and
      performance on the part of healthcare professionals, and knowledge and adherence
      to therapy on the part of patients. Addressing these barriers and treating
      patients appropriately can help address the potential health and economic
      consequences of osteoporosis.

PMID- 21882488
TI  - [Molecular diagnostics for monitoring and predicting therapeutic effect in
      cancer].

PMID- 21882489
TI  - Myofascial trigger points in subjects presenting with mechanical neck pain: a
      blinded, controlled study.
AB  - The aim of this study was to describe the differences in the presence of
      myofascial trigger points (TrPs) in the upper trapezius,sternocleidomastoid,
      levator scapulae and suboccipital muscles between patients presenting with
      mechanical neck pain and control healthy subjects. Twenty subjects with
      mechanical neck pain and 20 matched healthy controls participated in this study.
      TrPs were identified, by an assessor blinded to the subjects' condition, when
      there was a hypersensible tender spot in a palpable taut band, local twitch
      response elicited by the snapping palpation of the taut band, and reproduction of
      the referred pain typical of each TrP. The mean number of TrPs present on each
      neck pain patient was 4.3 (SD: 0.9), of which 2.5 (SD: 1.3) were latent and 1.8
      (SD: 0.8) were active TrPs. Control subjects also exhibited TrPs (mean: 2; SD:
      0.8). All were latent TrPs. Differences in the number of TrPs between both study
      groups were significant for active TrPs (P < 0.001), but not for latent TrPs (P >
      0.5). Moreover, differences in the distribution of TrPs within the analysed
      cervical muscles were also significant (P < 0.01) for all muscles except for both
      levators capulae. All the examined muscles evoked referred pain patterns
      contributing to patients' symptoms. Active TrPs were more frequent in patients
      presenting with mechanical neck pain than in healthy subjects.

PMID- 21882490
TI  - Cardiac remodeling rather than disturbed myocardial energy metabolism is
      associated with cardiac dysfunction in diabetic rats.
AB  - BACKGROUND: Diabetes mellitus (DM) alters the energy substrate metabolism in the
      heart and the early sign of diabetic cardiomyopathy is the diastolic dysfunction.
      Although it is known that the extracellular matrix must be altered in the
      presence of diabetes, its local regulation has not been fully elucidated. Our aim
      was to evaluate in vivo left ventricular (LV) structure; function and
      bioenergetics in streptozotocin (STZ) induced diabetes mellitus. METHODS: Cardiac
      function was evaluated using echocardiography in anesthetized Sprague-Dawley rats
      12 weeks after injection of STZ and in age-matched control rats before and after
      atrial pacing. In vivo 31P magnetic resonance spectroscopy was done to measure
      the phosphocreatine (PCr) to ATP ratio. Myocardial protein expression of
      metalloproteinases MMP-2, -9, tissue inhibitor TIMP-1, -2 and collagen was
      measured using Western blot. RESULTS: Bodyweight (BW) was decreased in diabetic
      rats. Heart weight/BW and LV mass/BW ratios were higher in diabetic animals
      compared to controls (2.3 +/- 08 vs 2.1 +/- 08 mg/g p <0.05). Heart rate was
      lower in diabetic rats (293 +/- 20 vs 394 +/- 36 bpm p <0.05). The velocity of
      circumferential shortening and peak aortic velocity were lower in diabetic
      animals and were more pronounced during atrial pacing. The basal PCr/ATP ratio
      was not different in the two groups. Total collagen was higher in diabetic rats
      (3.8 +/- 0.3 vs 2.9 +/- 01 mg/g, p <0.05). Protein expression of MMP-2 was
      significantly diminished in diabetic rats by ~ 60%, while MMP-9, TIMP-1 and -2
      were unchanged. CONCLUSION: Streptozotocin induced diabetes led to increased
      LV/bodyweight, increased collagen content, and diminished MMP-2 with no change in
      PCr/ATP. Therefore, remodeling rather than disturbed energetics may underlie
      diabetic cardiomyopathy.

PMID- 21882491
TI  - FPIN's clinical inquiries: hormone therapy for postmenopausal women with urinary
      incontinence.

PMID- 21882492
TI  - A pilot study on the effects of carvedilol on right ventricular remodelling and
      exercise tolerance in patients with systemic right ventricle.
AB  - BACKGROUND: Patients with atrial repair for transposition of the great arteries
      and patients with congenitally corrected transposition have a right ventricle
      (RV) in the systemic position and they may develop RV dysfunction and exercise
      intolerance with advancing age. No data is available on the effect of carvedilol
      in patients with dysfunctional systemic RV. METHODS: We studied with
      cardiovascular magnetic resonance (CMR), cardiopulmonary exercise testing, and
      standard 12-leads electrocardiogram, 8 adults (median age 26 years, range 18-31)
      with chronic stable heart failure and systemic RV dysfunction (6 patients with
      atrial repair and 2 patients with congenitally corrected transposition).
      Assessment was done before and after 12 months of carvedilol administration. The
      initial dose was 3.125 mg twice daily, and the target dose was 25 mg twice a day.
      RESULTS: Carvedilol administration was safe and the target dose was achieved in
      5/8 (62%) patients. Right ventricular end-diastolic (119 +/- 31 vs. 112 +/- 28
      ml/m2, p=0.01) and end-systolic volumes decreased (79 +/- 17 vs. 65 +/- 14 ml/m2,
      p=0.006), and RV ejection fraction improved (34 +/- 6 vs. 42 +/- 7%, p=0.004).
      Left ventricular ejection fraction increased (44 +/- 8 vs. 49 +/- 9%, p=0.01),
      suggesting a positive biventricular remodelling. Peak oxygen uptake did not
      change with carvedilol (26.8 +/- 5.3 vs. 27.3 +/- 5.7 ml O2/Kg/min, p=0.58),
      whereas exercise duration increased (13.4 +/- 2.6 vs. 17.3 +/- 3.1 min, p=0.008).
      CONCLUSIONS: In this small cohort, carvedilol administration was safe and it was
      associated with positive RV remodelling as well as improved exercise duration.

PMID- 21882493
TI  - [A 84-year-old man with apraxia and parkinsonism on his left side,who became
      bedridden for 6 years].

PMID- 21882494
TI  - [One hundred books which built up neurology (56)--Moritz Heinrich Romberg:
      "Klinische Ergebnisse. Gesammelt in dem Koniglichen poliklinischen Institut der
      Universitat" (1846)].

PMID- 21882495
TI  - MSD's patient-centered medical home pilot.

PMID- 21882496
TI  - Drug overdose with refractory bradycardia and hypotension.
AB  - BACKGROUND: In the emergency department physicians are often called upon to make
      decisions with limited information. Often the correct diagnosis and treatment
      hinge on one piece of information, which may be the key to the entire
      presentation. OBJECTIVE: We present a case report of a patient who presented with
      refractory bradycardia and hypotension who had over-dosed on calcium channel
      blockers as well as beta blockers. The underlying cause however was myxedema.
      Were it not for the presence of hypothermia, the correct diagnosis of myxedema
      secondary to severe hypothyroidism could have been missed. We also briefly review
      the pathophysiology and treatment of myxedema. CONCLUSION: We present a case of
      refractory bradycardia and hypotension in a patient who had overdosed on calcium
      channel blockers as well as beta blockers. Paying close attention to all the
      details of the case eventually uncovered the underlying severe hypothyroidism and
      myxedema. In the emergency department we are always called upon to make decisions
      with limited information. It is also paying close attention to all of the
      information presented that allows one to not miss any key pieces central to the
      final diagnosis.

PMID- 21882497
TI  - What is the best operative practice for small benign parotid pleomorphic adenoma?
AB  - Most surgeons will reduce the risk of recurrence and permanent facial nerve
      dysfunction with PSP for PPA with dissection and control of the facial nerve.
      High volume, very experienced parotid surgeons can offer ECD with the expectation
      of less transient facial nerve dysfunction, Frey's syndrome, and numbness. Long
      term recurrence rates await further reports.

PMID- 21882498
TI  - The "casual" patient is still your patient.

PMID- 21882499
TI  - [Projection of dentists in films].

PMID- 21882500
TI  - [Rotting children's dentition].

PMID- 21882501
TI  - [A part time job in dentistry is good to have for dental students. Yes].

PMID- 21882502
TI  - [A part time job in dentistry is good to have for dental students. No].

PMID- 21882503
TI  - [Caries: diagnostics, monitoring and guidance in good oral health behaviour. A
      reorientation].
AB  - Caries is a dynamic process which can develop either progressively or
      regressively under the all-determining influence of oral health behaviour.
      Management of caries therefore involves first of all: diagnostics, monitoring and
      preventive care and treatment which result in good oral health behaviour. The
      oral care provider should recognize all phases ofprogression of the caries
      process, and should be able to differentiate the symptoms which indicate an
      active or inactive process. A well maintained patient dossier is necessary to
      monitor this process over time. Following this procedure, the oral care provider
      is in a position to guide the patient with relevant information in order to
      achieve the final objective, good oral health.

PMID- 21882504
TI  - [Joseph Lister, pioneer of asepsis].

PMID- 21882505
TI  - [A patient with hypoaesthesia of the mandible].
AB  - In a patient with hypoaesthesia of the central region of the mandible, no oral
      cause could be found which could explain his complaint. Further examination by a
      neurologist and a specialist in internal medicine revealed the numb chin
      syndrome. The syndrome was caused by meningeal localisation of a high-grade B
      cell lymphoma stade IV. After intensive chemotherapy and radiotherapy of the
      skull, the complaints disappeared.

PMID- 21882506
TI  - [Work related health risks among dentist's assistants in Flanders, Belgium].
AB  - The aim of this research project was to learn more about work-related health
      risks among dental assistants in Flanders, Belgium. Forty-seven dental assistants
      completed an extensive questionnaire concerning ionized radiation, protection
      against infection and exposure to chemicals such as mercury, disinfectants and
      acrylates. Collective and personal means of protection, musculoskeletal disorders
      and work-related stress were also evaluated. Pain in the lower back, neck pain
      and shoulder pain were reported by, respectively, 15%, 17% and 22% of the
      respondents. Eczema resulting from skin irritation or contact-allergy was
      reported by 13%. Twenty-three percent of the assistants did not consistently make
      use ofa radiation badge; 80% wore a mouth mask and 33% wore protective glasses;
      and 82% was vaccinated against hepatitis B. Almost 10% reported verbal or
      physical aggression by patients. The mean stress score was 3.95 on a scale from 0
      to 10. The results may contribute to the formulation of a number of
      recommendations for the improvement of the health of dental assistants.

PMID- 21882507
TI  - [Oral surgery as the patient's immediate cause of death].
AB  - The purpose of this study was to determine how often patients have died after
      treatment by an oral surgeon in the Netherlands. A review of the literature
      showed that this kind of complication has rarely been described in international
      literature. Subsequently, a small questionnaire was sent to 274 Dutch oral
      surgeons; 140 questionnaires were returned (51% response). The oral surgeons
      participating in the survey had had, on average, 21 years of work experience and
      4.3% were women. Forty percent of the respondents confirmed that they had
      experienced the death of a patient after oral surgery. Most (18 patients) died
      after a dental extraction. The most important causes of death were post-operative
      spreading of an infection (15 patients), failing to survive oncology treatment (9
      patients) and as the third cause of death, heart and/or lung failure was named (6
      patients).

PMID- 21882508
TI  - [Placing of oral implants in patients using bisphosphonates].
AB  - Dentists are with increasing frequency confronted with patients who are being
      treated with bisphosphonates for certain bone diseases, hypercalcaemia, and bone
      metastases of solid malignancies. A side effect of the use of bisphosphonates is
      osteonecrosis of the jaw. Bisphosphonate-induced osteonecrosis of the jaw occurs
      mainly after treatment with intravenous bisphosphonates and to a much lesser
      extent after oral administration of bisphosphonates. The question remains whether
      oral implants can be safely placed in patients using bisphosphonates. A survey of
      the literature shows that the risk ofosteonecrosis of the jaw and loss of oral
      implants is not increased when the implants are placed within 3 years after
      starting treatment with oral bisphosphonates. After this period there is the
      possibility of a slightly increased risk of complications. The possibility of
      complications is higher in patients receiving the intravenous bisphosphonates,
      and, therefore, elective surgical treatments is not advocated.

PMID- 21882510
TI  - The CDT 2011-2012 changes.

PMID- 21882509
TI  - [Permanent molar crypts in the human mandible].
AB  - A few decades ago, relatively little was known concerning the pre-eruptive
      spatial development of permanent molars. The material that formed the basis for
      this study consisted of 114 dry human mandibles of young children and
      adolescents. Measurements were made on radiographs of the bony crypts in which
      the tooth germs had existed ante mortem and the pattern of spatial development
      was studied macroscopically and histologically. The findings revealed a
      consistent developmental pattern, in which the means of expansion of the crypts
      of the second and third molars, prior to crown-calcification, displayed strong
      similarities. The displacements as they were indicated by the measurements on the
      radiographs were confirmed by the macro- and micro-morphological study of the
      bone surfaces. The mesio-distal relationship of adjacent crypts appeared to be
      influenced by morphological characteristics of the mandible early on in their
      development. New insights have not been achieved subsequently, up to the present
      day, because little follow-up research into the spatial development of the bony
      crypts has been undertaken.

PMID- 21882511
TI  - The power of the pack can be insurmountable.

PMID- 21882512
TI  - Working to ensure patients have the quality of care they deserve.

PMID- 21882513
TI  - IOM issues its first report on Medicare's GPCIs-IMS' quest for GPCI equity
      continues.

PMID- 21882514
TI  - Changing environment, student interest curriculum.

PMID- 21882515
TI  - A year of independence.

PMID- 21882516
TI  - Reconfiguration. Talking services into shape.

PMID- 21882517
TI  - Legal. Foundation trusts face the future of boom and bust.

PMID- 21882518
TI  - Patient involvement. Loud and clear: nine shouts for the Health Bill.

PMID- 21882519
TI  - [Research progress of new antibacterial drugs that target bacterial quorum
      sensing systems].
AB  - In recent years, antibiotic resistance of bacteria has become a global health
      crisis. Especially, the new class of "superbug" was found in South Asia, which is
      resistant to almost known antibiotics and causes worldwide alarm. Through the
      underlying mechanisms of bacterial pathogenecity, the expression of many pathogen
      virulence factors is regulated by the process of quorum sensing. Screening
      efficient quorum sensing inhibitors is an especially compelling approach to the
      future treatment of bacterial infections and antibiotic resistance. This article
      focuses on bacterial quorum sensing system, quorum sensing screening model for in
      vitro and evaluation of animal models in vivo, recent research of quorum sensing
      inhibitors and so on.

PMID- 21882520
TI  - [Advances in the structure-activity relationship study of natural flavonoids and
      its derivatives].
AB  - Flavonoids are a large class of compounds widely distributed in nature. Many
      pharmacological activities of flavonoids have been reported such as anti-cancer,
      antioxidant, anti-inflammatory, hepatoprotective, antithrombotic, vasodilator,
      antiviral, antibacterial, antiallergic, and so on. In recent years, domestic and
      foreign research groups choose natural flavonoids and optimize their chemical
      structures in order to develop a number of new derivatives with stronger
      pharmacological activities. As part of the mechanisms are not clear, we need to
      strengthen in-depth research in the SAR (structure-activity relationship) study
      for targeted and efficient structure optimization. This paper systematically
      summarize current researches in the SAR studies of flavonoids and their
      derivatives, which can serve as a reference for synthesizing new flavonoid
      derivatives.

PMID- 21882521
TI  - [Progress of the hydrokinetic chromatography and its application in the
      characterization of particulate drug delivery systems].
AB  - In the present paper, the basic principles, the device and the analytical method
      of the hydrodynamic chromatography (HDC) were summarized, which is most widely
      used in hydrokinetic chromatography. The application of the hydrodynamic
      chromatography in the determination of the particle size and size distribution of
      the particulate drug delivery system was also reviewed. The method can determine
      the particle size of nano- and micron-scale particulate drug delivery systems
      rapidly. And this method also has the advantages of economic, convenient and no
      damage to the samples. In summary, there will be a good prospect for the
      application of HDC in the determination of particle size distribution features of
      particulate drug delivery systems.

PMID- 21882522
TI  - [Research progress of enhancing quantitative sensitivity by using LC-MS(n) with
      derivatization method in bio-matrices].
AB  - Liquid chromatography/mass spectrometry (LC-MS(n)) has been essential to a large
      number of quantitative analytical applications in drug research, and especially
      in the drug PK/PD research, due to its high sensitivity and high specificity. But
      following the appearance of drugs with high activity and low dosage and the
      especial structural compounds, a number of limitations of LC-MS(n) have been
      noted. Derivatization changes the structure of drugs and therefore changes their
      physical and chemical properties, resulting in high ionization efficiency, low
      matrix effect and low disturbance by inorganic salts and endogenous compounds in
      LC-MS(n). In this article, recent progress in the research of the chemical
      derivatization strategy with LC-MS(n) is reviewed on breakthrough of some LC
      MS(n) limitations, in particular focusing on the applications involving some
      drugs in bio-matrices.

PMID- 21882523
TI  - [Effect of pinocembrin on brain mitochondrial respiratory function].
AB  - There are growing evidences that pinocembrin has better neuroprotective effect.
      In the present study, the effect of pinocembrin on mitochondrial respiratory
      function was evaluated in global brain ischemia/ reperfusion (4-vessel occlusion,
      4-VO) rats. The results showed that pinocembrin improved the respiratory activity
      of 4-VO brain mitochondria, through increasing ADP/O, state 3 respiration state
      (V3), respiration control rate index (RCI) and oxidative phosphorylation rate
      (OPR). And then, the effect of pinocembrin on brain mitochondria was verified in
      vitro. The results showed that pinocembrin increased ADP/O, state 3 respiration
      state, respiration control rate index, oxidative phosphorylation rate in
      NADH/FADH2 dependent respiratory chain and decreased state 4 respiration state
      (V4) in NADH dependent respiratory chain. Pinocembrin improved ATP content in
      brain mitochondria in vitro and in SH-SY5Y cells.

PMID- 21882524
TI  - [Effects of yin qiaojiedu soft capsule on influenza virus load and M1 expression
      in mice].
AB  - This study is to investigate the treatment of YinQiaojiedu soft capsule for
      influenza virus A/PR8/34 (H1N1) infection. The model of pneumonia was established
      by dropping influenza virus into the nose of normal mice, and the lung index and
      death rate were observed. Real time RT-PCR and Western blotting technique were
      used to detect the virus load and the relative expression of M1 protein in lungs
      of mice on the 1st, 3rd, 5th and 7th day after infection. The results showed that
      YinQiaojiedu soft capsule in 1 g x kg(-1) and 0.5 g x kg(-1) dose groups can
      decrease the lung index significantly on the 3rd, 5th and 7th day after being
      infected (P < 0.05, P < 0.01), and the number of death in the two groups of
      animals decreased significantly. YinQiaojiedu soft capsule in 1 g x kg(-1) dose
      group can decreased virus load at each time point, and lower it in 0.5 g x kg(-1)
      dose group at the 3rd, 5th and 7th day (P < 0.05, P < 0.01). YinQiaojiedu soft
      capsule can decrease the relative expression of M1 protein in lungs of mice, 1 g
      x kg(-1) and 0.5 g x kg(-1) dose groups are significantly lower in expression of
      M1 protein compared with model group at the 3rd and 7th day (P < 0.05, P < 0.01).
      It can be concluded that YinQiaojiedu soft capsule exerts antiviral effects
      against influenza virus by downregulating expression of virus load and M1
      protein.

PMID- 21882525
TI  - Effects of bicyclol on the activity and expression of CYP450 enzymes of rats
      after partial hepatectomy.
AB  - The present study was performed to investigate the effect of bicyclol on hepatic
      microsomal cytochrome P450 (CYP) activity, as well as gene and protein
      expressions in rats after partial hepatectomy (PH). Bicyclol (300 mg x kg(-1))
      was given to rats subjected to 70% hepatectomy three times before operation. At 6
      and 48 h after PH, blood and liver tissue samples were collected for the
      measurement of serum alanine aminotransferase (ALT), hepatic microsomal
      malondialdehyde (MDA) and total hepatic CYP content. The activities of four CYP
      isozymes were detected with liquid chromatography-mass spectrometry (LC-MS) and
      the gene and protein expressions were determined by RT-PCR and Western blotting
      assay. As a result, bicyclol pretreatment markedly inhibited the elevation of
      serum ALT and hepatic microsomal MDA, and prevented the decrease of total hepatic
      CYP content in PH rats. In addition, bicyclol significantly attenuated the
      reduction of CYP2C6 activity and mRNA expression, as well as the reduction of
      CYP2C11 activity in PH rats. Bicyclol can inhibit the decrease of CYP3A1/2
      activity, and up-regulate the mRNA and protein expressions of CYP3A1 and CYP2E1.
      These results showed that bicyclol pretreatment might ameliorate abnormality in
      CYP450 isoforms during liver regeneration after PH, and this protective effect
      was likely due to its anti-oxidative property and enzyme induction.

PMID- 21882526
TI  - [The semi-quantitative method for evaluating lipid accumulation in pancreas of
      diabetic mice].
AB  - To investigate the semi-quantitative method for evaluating the lipid accumulation
      in pancreas, the KKAy mice, a classical type 2 diabetes mellitus model mice, were
      used and treated with rosiglitazone (Rosi); and the age-matched C57BL/6J mice
      were used as normal control. Pancreas was fixed quickly for histological
      examination with HE staining. For the estimation of the lipid accumulation in
      pancreas, semi-quantitative method was designed: the number and the size of
      islet, lipid accumulation in islet and in exocrine gland were observed and the
      integrative score calculated under the microscope, separately. In KKAy mice, the
      characteristics of the increased amount of islet, the enlarged area of islet, an
      abundance of large vacuolations, lipid droplets, and fat proliferation were
      exposed frequently, and the integrative score increased 2.1 folds compared with
      that in C57BL/6J mice. Meanwhile, the levels of serum glucose, insulin, and
      triglyceride (TG) were 1.7, 18.0, and 9.0 times as those in C57BL/6J mice,
      respectively. With the rosiglitazone (10 mg x kg(-1)) treatment, compared with
      that in KKAy mice, the pancreatic pathological changes were ameliorated
      significantly, and the integrative score in KKAy + Rosi mice decreased by 28.9%;
      and the levels of serum glucose, insulin, and triglyceride decreased by 48.3%,
      81.3% and 64.1%, respectively. It showed there is a correlation between the
      pancreatic pathological semi-quantitative score and the values of serum
      parameters. In conclusion, this semi-quantitative scoring method is simple and
      objective for the evaluation of lipid accumulation in pancreas of mice.

PMID- 21882527
TI  - Lipid-lowering effect of cordycepin (3'-deoxyadenosine) from Cordyceps militaris
      on hyperlipidemic hamsters and rats.
AB  - 3'-Deoxyadenosine, so-called cordycepin, is a bioactive component of the fungus
      Cordyceps militaris. It has been known to exhibit multiple-biological effects
      including: modulation of immune response, inhibition of tumor growth, hypotensive
      and vasorelaxation activities, and promoting secretion of adrenal hormone. To
      investigate its lipid-lowering effect, hyperlipidemic hamsters and rats fed by
      high-fat diet were both administered orally with cordycepin extracted from
      Cordyceps militaris for four weeks. The levels of lipids in hamsters and rats
      were measured enzymatically before and after the administration of cordycepin
      (12.5, 25 and 50 mg x kg(-1)). The results suggested that levels of serum total
      cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C)
      and very low density lipoprotein cholesterol (VLDL-C) increased markedly in the
      two animal models by feeding high-fat diet. Meanwhile, cordycepin reduced levels
      of serum TC, TG, LDL-C, VLDL-C as well as LDL-C/HDL-C (high density lipoprotein
      cholesterol) and TC/HDL-C ratios. In concert with these effects, an increase in
      lipoprotein lipase (LPL) and hepatic lipase (HL) activity afforded by cordycepin
      was considered to contribute to the regulation on lipid profiles. Furthermore, no
      toxicity of cordycepin was observed by intragastric administration at the maximal
      tolerant dose in ICR mice for 14 days. The exact lipid-lowering effect of
      cordycepin needs further investigation.

PMID- 21882528
TI  - [The interaction between genistein and beta-glucosidase].
AB  - The interaction between genistein and beta-glucosidase was studied using
      fluorescence quenching method and synchronous fluorimetry. The binding reaction
      was simultaneously studied by the AutoDock 4.2 molecular docking model. Data from
      fluorescence spectroscopy indicated that these interactions resulted in the
      endogenous fluorescence quenching of beta-glucosidase, which belongs to a static
      quenching mechanism. The calculated binding constants were 3.69 x 10(4), 3.06 x
      10(4) and 2.36 x 10(4) L x mol(-1) at 17, 27 and 37 degrees C, respectively. The
      evidences from synchronous fluorescence showed the effect of genistein on the
      microenvironment around beta-glucosidase in aqueous solution. The inhibition test
      showed that the activity of beta-glucosidase could be inhibited by genistein. The
      determined bimolecular rate constant (k(i)) was 1.2 x 10(3) (mol x L(-1)(-1) x
      min(-1). Molecular docking was performed to reveal the possible binding mode or
      mechanism and suggested that genistein could bind strongly to beta-glucosidase.
      The results revealed that genistein tended to bind with beta-glucosidase mainly
      by hydrogen bond and hydrophobic interaction as well as electrostatic forces.

PMID- 21882529
TI  - [Synthesis and antiviral activities of geldanamycin analog TC-GM in vitro].
AB  - In order to find antiviral compounds with novel structures, geldanamycin and
      lamivudine with different antiviral mechanisms were conjunctively synthesized to
      acquire a new compound TC-GM, and the antiviral activity of TC-GM was measured.
      The antiviral activity against HIV-1 was examined by p24 antigen ELISA kit. The
      activity against HBV was examined by dotblot. The activity against HSV and CoxB
      virus was examined by CPE. TC-GM exhibited broad-spectrum antiviral activities
      similarly like geldanamycin. TC-GM inhibited the replication of different
      viruses, including HIV-1, HBV, HSV 1 and 2, CoxB6. TC-GM showed more potent
      inhibitory activity against HIV-1 and HBV than other detected virus.

PMID- 21882530
TI  - [Design, synthesis and evaluation of novel 2H-1, 4-benzodiazepine-2-ones as
      inhibitors of HIV-1 transcription].
AB  - HIV-1 trans-activator of transcription (Tat) plays a critical role in HIV-1
      transcription. Based on the beta-turn motif present in HIV-1 Tat, a series of
      novel benzodiazepine analogs were designed as beta-turn mimetics and prepared
      from p-chloro-nitrobenzene/2-phenylacetonitrile, p-toluidine/benzoyl chloride, or
      (Z)-7-nitro-5-phenyl-1H-benzo[e][1, 4]diazepin-2(3H)-one (nitrazepam) through
      different synthetic routes. Preliminary biological evaluation indicated that
      compound 30 exhibited inhibitory activity on HIV-1 tat-mediated LTR transcription
      with EC50 of 25.0 micromol x L(-1) and showed no obvious cytotoxic effects on TZM
      BI cells under the concentration of 100 micromol x L(-1).

PMID- 21882531
TI  - [Effect of OATP1B1 521T --> C heterogenesis on pharmacokinetic characterstics of
      rosuvastatin in Chinese volunteers].
AB  - This study is to report the effect of OATP1B1 gene mutation in the 521T --> C in
      Chinese human on the pharmacokinetics of rosuvastatin and guide the reasonable
      clinical application of rosuvastatin by the feature of genetic polymorphism of
      OATP1B1. Plasma samples were determined with LC-MS: the analyte and internal
      standard pitavastatin were both analyzed by MS in the ESI, m/z was 480.0 for
      rosuvastatin and 420.0 for the IS, separately. Genotyping of OATP1B1 was
      determined with the method of polymerase chain reaction--amplification refractory
      mutation system targeted at 40 healthy volunteers and showed that there were 7
      subjects with 521T --> C mutant, accounting to 17.5% of total and wild type
      homozygote accounted to 82.5%. It was found that there were significant
      differences between OATP1B1 mutation in the 521T --> C and wild type homozygote
      for rosuvastatin pharmacokinetic process in Chinese human. In contrast to OATP1B1
      wild type group, OATP1B1 mutation group's absorption degree increased,
      elimination process decreased. The OATP1B1 mutation should be noted for guiding
      the reasonable application of rosuvastatin during its clinical use.

PMID- 21882532
TI  - [Tissue distribution of arsenic of liushen pills and realgar].
AB  - This study is to report the tissue distribution of arsenic after giving different
      doses of realgar and Liushen pills to Beagle dogs, in order to provide basis for
      the safety evaluation of Liushen pills. ICP-MS was used to measure arsenic
      concentration, and HPLC-ICP-MS was used to analyze arsenic speciation. The
      concentration of total arsenic and As(III) + DMA (arsenite + dimethylarsenic
      acid) increased with dosing of realgar. Total arsenic concentration in most
      tissues and As(III) + DMA concentration in all tissues of Liushen pills group are
      lower than that of realgar group, but AsB concentration in liver, spleen and
      kidney of Liushen pills group increased. The concentration of total arsenic
      showed a dose-dependent manner with dosage administered. It was indicated that
      components in Liushen pills can reduce solubility of arsenic in realgar, which
      may decrease toxicity of realgar.

PMID- 21882533
TI  - [Microcosmic mechanisms of amorphous indomethacin crystallization and the
      influence of nano-coating on crystallization].
AB  - Amorphous drugs have higher solubility, better oral bioavailability and are
      easier to be absorbed than their crystalline counterparts. However, the amorphous
      drugs, with weak stability, are so easy to crystallize that they will lose the
      original advantages. Polarization microscope, scanning electron microscope,
      differential scanning calorimetry, X-ray diffractomer and Raman spectroscopy were
      used to study the microcosmic crystallization mechanisms of amorphous indometacin
      and the performance of the drug crystals. The results showed that the growth rate
      of amorphous indometacin crystals at the free surface was markedly faster than
      that through the bulk, and that the crystal growth rate decreased observably
      after spraying an ultrathin melting gold (10 nm) at the free surface of the drug.
      These results indicated that the high growth rates of amorphous drugs crystals at
      the free surface were the key to their stability and that an ultrathin coating
      could be applied to enhance the stability of amorphous drugs.

PMID- 21882534
TI  - In vitro study of transdermal penetration and iontophoresis of hepatitis B
      vaccines through rat skin.
AB  - In vitro percutaneous delivery of hepatitis B vaccines was investigated in order
      to assess the penetration of vaccine under passive diffusion and iontophoresis
      conditions. The study was carried out using Franz vertical diffusion cell through
      the hairless abdominal skin of Sprague-Dawley (SD) rats. Enzyme-linked
      immunosorbent assay (ELISA) was used to determine the cumulative amount of
      permeation and the retention amount of drug in skin. Passive diffusion alone
      resulted in less skin permeation and retention of hepatitis B vaccines, only (2.1
      +/- 0.1) ng x cm(-2) and (2.3 +/- 0.1) ng x cm(-2) after 24 h when the initial
      concentration of vaccine in the donor compartment was 23 microg x mL(-1) and 46
      microg x mL(-1), respectively. After removing the stratum corneum, the permeation
      and retention amount of hepatitis B vaccines increased to (383.7 +/- 86.2) ng x
      cm(-2) and (16.8 +/- 4.6) ng x cm(-2), respectively, 171.6-folds and 2.1-folds
      more than that from its intact skin with the drug loaded at 46 microg x mL(-1).
      Iontophoresis induced a significant increase of cumulative and retention amount
      of hepatitis B vaccines through the skin (P < 0.05). Application of iontophoresis
      significantly enhanced the permeation of hepatitis B vaccines (P < 0.05) by 2.7
      folds and 6.6-folds for the intact skin, and by 1.6-folds and 1.8-folds for the
      tape-stripped skin with initial drug loading of 23 microg x mL(-1) and 46 microg
      x mL(-1), respectively. Iontophoresis also significantly increased the amount of
      drug retained in the skin. After applying iontophoresis for 6 h, the amount of
      skin retention was nearly the same as passive diffusion for 24 h both from intact
      skin [(16.8 +/- 4.6) ng x cm(-2) vs (13.3 +/- 5.4) ng x cm(-2)] (P > 0.05) and
      tape-stripped skin [(36.7 +/- 14.1) ng x cm(-2) vs (26.8 +/- 11.2) ng x cm(-2)]
      (P > 0.05). Overall, these findings revealed that the transportation efficiency
      of bioactive substance like hepatitis B vaccines may be improved by
      iontophoresis, which can be potentially used in the field of transcutaneous
      immunization.

PMID- 21882535
TI  - [Water in oil microemulsions containing NaCl for transdermal delivery of
      fluorouracil].
AB  - This study is to prepare the W/O microemulsion containing NaCl and fluorouracil
      (5-Fu) as a model drug to investigate the transdermal characteristics and skin
      irritation of the microemulsion in vitro. Isopropylmyristate (IPM) acting as oil
      phase, Aerosol-OT (AOT) as surfactant, Tween 85 as cosurfactant, NaCl solution
      was added dropwise to the oil phase to prepare W/O microemulsion at room
      temperature using magnetic stirring, and then 5-Fu powder was added. According to
      the area of microemulsion based on the pseudo-tertiary phase diagrams, the
      optimum formulation was screened initially. And the permeation flux of
      fluorouracil across excised mice skin was determined in vitro using Franz
      diffusion cells to study the influence of the amount of water and the drug
      loading capacity and optimize the formulation further. Refer to 5-Fu cream, the
      irritation of microemulsion on the rat skin was studied. The optimum formulation
      was composed of 0.7% (w/v) 5-Fu, 50% NaCl solution (0.05 mol x L(-1)), 20% mix
      surfactant (AOT/Tween 85, K(m) = 2) and 29.3% oil (IPM). The cumulative amount of
      fluorouracil permeated in 12 h was (2 013.4 +/- 41.6) microg x cm(-2), 20.23
      folds and 10.38 folds more than 0.7% fluorouracil aqueous solution and 2.5% (w/w)
      fluorouracil cream, respectively. Microemulsion exhibited some irritation, but
      could be reversed after drug withdrawal. The addition of NaCl significantly
      increased the content of water and the drug loading in microemulsion systems. The
      NaCl/AOT-Tween 85/IPM microemulsion system promoted the permeation of
      fluorouracil greatly, which may be a promising vehicle for the transdermal
      delivery of fluorouracil and other hydrophilic drug.

PMID- 21882536
TI  - [Thermosensitive in situ gel of boanmycin hydrochloride for injection].
AB  - Poloxamer F127, poloxamer F68 and hydroxypropyl methylcellulose K4M were used to
      prepare the thermosensitive in situ gel of boanmycin hydrochloride for injection.
      Its gelation temperature, rheological behavior, texture characteristics, scanning
      electron microscopy, in vitro and in vivo drug release were evaluated. These
      results showed that the formulation was a fluid solution at room temperature,
      which could become semisolid at the temperature of 37 degrees C, and the
      thermally induced sol-gel transition allowed to be injectable and in situ
      setting. The formulation was constructed into a tridimensional network at
      gelation temperature. The drug release was controlled by the diffusion of the
      drug and the erosion of the gelmatrix. The pharmacokinetics indicated that the
      drug could be released slowly for up to 48 hours after subcutaneous
      administration in rats.

PMID- 21882537
TI  - Microbial glycosylation of cardamonin by Mucor spinosus.
AB  - Microbial transformation of cardamonin by Mucor spinosus (CGMCC 3.3450) in
      preparative scale resulted in the isolation of two new products. Their structures
      were elucidated unambiguously by ESI-MS, 1H NMR, 13C NMR and 2D NMR spectra
      analyses as 4-O-beta-D-glucopyranosyl-6-hydroxy-2-methoxychalcone (1, 4-GluC) and
      6-O-beta-D-glucopyranosyl-4-hydroxy-2-methoxychalcone (2, 6-GluC), respectively.
      The time-course of biotransformation by M. spinosus showed that both 4-GluC and 6
      GluC appeared on the 2nd day. The optimal biotransformation temperature was 28
      degrees C, the optimal biotransformation time was 72 h and the optimal
      concentration for cardamonin was 40 mg x mL(-1). This is the first time for
      successful microbial glycosylation of cardamonin in present research.

PMID- 21882538
TI  - [Effects of puerarin on proliferation and differentiation of umbilical cord
      mesenchymal stem cells into osteoblasts in vitro].
AB  - This study is to investigate the effects of puerarin on the proliferation and
      differentiation of umbilical cord mesenchymal stem cells (MSCs) into osteoblasts.
      Umbilical cord MSCs were cultured by tissue adherence and the third passage of
      cells was used in the experiment. The effect of puerarin on proliferation of
      umbilical cord MSCs was measured with MTT. The effects of puerarin on umbilical
      cord MSCs were evaluated by ALP immunohistochemisty and von kossa staining. The
      OD value decreased with the increase of puerarin concentration. On 7th day, ALP
      expression of puerarin group was higher than that of control group. On 14th day,
      ALP staining showed that the positive rate of puerarin group was higher than that
      of control group. Von kossa staining showed the quantity of calcium nodules was
      higher in puerarin group than that of control group. Puerarin can promote the
      umbilical cord MSCs to differentiate into osteoblasts and has an effect on the
      proliferation of umbilical cord MSCs.

PMID- 21882539
TI  - [Sedative, hypnotic and anticonvulsive effects of an adenosine analogue
      WS090501].
AB  - This study is to examine the sedative, hypnotic and anticonvulsive effects of an
      adenosine analogue, WS090501. The spontaneous locomotor activity was recorded by
      open field equipment, and the EEG of rats was recorded by polyphysiograph.
      Pentylenetetrazol (PTZ)-induced seizure model was used. The spontaneous locomotor
      activity was decreased by WS090501 at various doses (0.06, 0.13, and 0.25 mg x
      kg(-1)), and the decreasing rate was 28.4%, 47.1% and 61.2% respectively.
      Furthermore, the effect of WS090501 on spontaneous locomotor activity of mice can
      be antagonized by DPCPX, a selective adenosine A1R antagonist, but cannot be
      antagonized by SCH58261, a selective adenosine A2AR antagonist. The NREM sleep
      was significantly increased by WS090501 (0.05 and 0.2 mg x kg(-1)), and the
      increasing rate was 27.6% and 102.8%, respectively, at 6th hour after
      administration. The REM sleep decreased significantly at the higher dose. PTZ
      induced serious convulsion in mice. The latency of convulsion was prolonged, and
      the number of seizure and mortality decreased after administration of WS090501.
      These results show that WS090501 has potent sedative, hypnotic and anticonvulsive
      effects, which may be mediated through adenosine A1R.

PMID- 21882540
TI  - [Visual presentation of psychiatric clinical decision-making by "graphic
      assessment sheet for diagnoses and treatments"].
AB  - Psychiatrists often have to treat patients even when the clinical information is
      insufficient to make a definite diagnosis. This is the case especially when we
      are treating first-visit outpatients or inpatients who have just been admitted.
      One of the causes of information insufficiency is a delay in obtaining clinical
      information on the patient, and another is a lack of characteristic
      manifestations of the disease because of an immature developmental stage. Even in
      such situations, however, clinicians have to make reasonable judgements using the
      information that is available at that time. The framework for making judgements
      on such occasions, or "the framework of decision-making under imperfect
      information conditions", is becoming more and more important in psychiatric
      clinical practice in Japan for the following reasons. First, team members in
      charge of a patient became very heterogeneous in terms of their career and
      motivation after the start of the new post-graduate clinical training system in
      Japan several years ago, resulting in a higher risk of miscommunication.
      Secondly, the need for precise explanation to patients and their families has
      become crucial in recent years as the result of various social changes. Ota T,
      one of the authors, once put forward the framework of decision-making under
      imperfect-information conditions on the basis of Bayesian statistics. In the
      present paper, in consideration of the above background, we devised a sheet for
      visualizing the above framework so that relevant staff could share the clinical
      decision-making process. Specifically, we visually arranged on a sheet of paper
      the components and variables of the framework, so that the staff could
      communicate with each other explicitly and precisely about the estimated
      probability of each possible disease, merits and demerits of each treatment
      option, etc. We employed the sheet on treating patients in our acute psychiatric
      ward, 2 of whom are presented in the paper. Discussions were made on the
      usefulness, limitations, and remaining problems.

PMID- 21882541
TI  - [Molecular pathophysiology of schizophrenia and preventive strategy in pubertal
      period].
AB  - A novel frameshift mutation in glyoxalase 1 (GLO1) gene was detected in a patient
      with schizophrenia of a pedigree with multiple affected individuals. The patient
      carrying the mutation showed decreased enzymatic activity by 50%, 3.7 times high
      level of advanced glycation end products (AGEs) that is substrate of GLO1 and 20%
      of serum vitamin B6 compared to controls. Case-control study of GLO1 gene
      suggested that Ala allele of Glu111Ala was associated with schizophrenia. In
      vitro study using COS-7 cells transfected with cDNA of GLO1 yielded that
      enzymatic activity is lower in GLO1 with Ala111 than that of Glu111. The
      homozygotes of Ala111 showed 16% decreased GLO1 activities in RBC as compared
      with that of Glu111/Ala111 and Glu111/Glu111. Plasma AGEs levels were
      significantly high and serum vitamin B6 was significantly low in 45
      schizophrenics than that of 61 control subjects. Supplementation of vitamin B6 to
      cases with the genetic defect of GLO1 before onset of psychosis is suggested to
      be possible strategy for prevention of schizophrenia until pubertal stage since
      such mutation carriers could have been exposed by high level of AGEs for a long
      time before disease onset.

PMID- 21882542
TI  - [Integrative studies for early psychosis: toward realizing youth mental health].
AB  - The editorial of the new-year issue of Nature 2010 features "A decade for
      psychiatric disorders". The DALY estimation clearly shows that psychiatric
      disorders are the top source for burden of diseases to the individual life and
      society. Schizophrenia is a most devastating psychiatric disorder in which the
      onset is usually at youth and the cognitive dysfunction persists for life-long in
      some patients. Schizophrenia is associated with neurodevelopmental abnormalities.
      It has been unknown whether post-onset progressive pathology is also present in
      schizophrenia until the recent sophistication of in vivo neuroimaging techniques.
      Longitudinal neuroimaging studies on first-episode schizophrenia have shown a
      progressive deterioration of structure and function of neocortical regions in the
      early stage of the disorder. Insult to dendritic spines through glutamatergic
      dysfunction may underlie this process, which may in turn be a promising molecular
      target for intervention to improve the functional outcome of schizophrenia. More
      recently, the question of whether early intervention can be targeted at prodromal
      stage of schizophrenia has called special attention in psychiatry. In University
      of Tokyo, the integrative neuroimaging studies for schizophrenia targeting early
      intervention and prevention (IN-STEP) is ongoing. Through these efforts, we would
      like to contribute to the establishment of "youth mental health", where every
      youth in the community can know, prevent, and have easy access to needs- and
      value-based services, and pursue mental well-being and recovery.

PMID- 21882543
TI  - [On the case management of youth with early psychosis].
AB  - Case management lies at the foundation of clinical activities for youth with
      early psychosis. While introducing the systems and skills accumulated in Anglo
      American countries, the author affirms tasks associated with care management in
      Japan. The characteristics of case management for youths with early psychosis are
      as follows: 1) a primary therapeutic model, 2) emphasizing engagement by means of
      outreach, 3) limiting caseloads for the sake of fostering collaborative
      relationships, 4) adopting a method of active brokerage, and 5) establishing time
      limits of two or three years. The author calls for the establishment of a new
      training system for implementing these activities in Japan, due to the existence
      of significant misunderstandings of care management in that country.

PMID- 21882544
TI  - [Childhood-onset schizophrenia and schizophrenia spectrum disorder].
AB  - The concept, diagnosis and clinical picture of childhood-onset schizophrenia were
      presented. The cases with childhood-onset schizophrenia were classified into 4
      groups according to their process of growth and development. Furthermore, it has
      been suggested that the progression of childhood-onset schizophrenia developed on
      the basis of neuro-developmenal hypothesis might contribute to the understanding
      of adult onset schizophrenia and early diagnosis and intervention of
      schizophrenia.

PMID- 21882545
TI  - [The neurotic disorders].
AB  - The clinical practice of child and adolescent psychiatry includes encounters with
      disorders not particular to childhood and adolescence, but seen in adulthood as
      well. For example, among the neurotic disorders, obsessive-compulsive disorder
      can be seen from around 3 years of age, with rapid rise in prevalence from around
      age 10. Increase is also seen in cases of anorexia nervosa from around age 11.
      This report examines the association between disorders in childhood and
      adolescence, in comparison to that in adulthood, with focus on obsessive
      compulsive disorder. To start with, the characteristics of childhood onset cases
      with onset under age 7 were reviewed, revealing a relatively large proportion of
      subjects with experience of separation anxiety. Analyses revealed the possibility
      of anticipating obsessional tendencies in the parents of such subjects. Further
      clarification of the features of such early onset cases is hoped for in future.
      Next, we conducted a literature review comparing the characteristics of child and
      adolescent obsessive-compulsive disorder with that in adulthood. It has been
      determined that obsessive-compulsive symptoms in childhood and adolescence have a
      relatively unyielding 4-factor construct that persists through life, namely: 1)
      symmetry factor, 2) forbidden thoughts factor, 3) cleaning factor, and 4)
      hoarding factor. Of these, children with primary symptoms of hoarding are said to
      have poorer long-term diagnoses than children with other symptoms. Another point
      of note is the presence of large disparity regarding the prognosis of cases with
      concomitant tics. While the prognosis of childhood-obsessive compulsive disorder
      is generally favorable in many reports, the need for caution has also been noted
      regarding the possibility of transition on to schizophrenia in more than just a
      few cases.

PMID- 21882546
TI  - Modelling the energy demands of aerobic and anaerobic membrane bioreactors for
      wastewater treatment.
AB  - A modelling study has been developed in which the energy requirements of aerobic
      and anaerobic membrane bioreactors (MBRs) are assessed in order to compare these
      two wastewater treatment technologies. The model took into consideration the
      aeration required for biological oxidation in aerobic MBRs (AeMBRs), the energy
      recovery from methane production in anaerobic MBRs (AnMBRs) and the energy
      demands of operating submerged and sidestream membrane configurations. Aeration
      and membrane energy demands were estimated based on previously developed
      modelling studies populated with operational data from the literature. Given the
      difference in sludge production between aerobic and anaerobic systems, the model
      was benchmarked by assuming high sludge retention times or complete retention of
      solids in both AeMBRs and AnMBRs. Analysis of biogas production in AnMBRs
      revealed that the heat required to achieve mesophilic temperatures (35 degrees C)
      in the reactor was only possible with influent wastewater strengths above 4-5 g
      COD L(-1). The general trend of the submerged configuration, which is less energy
      intensive than the sidestream configuration in aerobic systems, was not observed
      in AnMBRs, mainly due to the wide variation in gas demand utilized in anaerobic
      systems. Compared to AeMBRs, for which the energy requirements were estimated to
      approach 2 kWh m(-3) (influent up to 1 g COD L(-1)), the energy demands
      associated with fouling control in AnMBRs were lower (0.80 kWh m(-3) for influent
      of 1.14 g COD L(-1)), although due to the low fluxes reported in the literature
      capital costs associated with membrane material would be three times higher than
      this.

PMID- 21882547
TI  - The role of external and internal mass transfer in the process of Cu2+ removal by
      natural mineral sorbents.
AB  - The kinetics of Cu2+ sorption on to zeolite, clay and diatomite was investigated
      as a function of initial metal concentrations. For consideration of the mass
      transfer phenomena, single resistance models based on both film and intraparticle
      diffusion were tested and compared. The obtained results suggested that the rate
      limiting step in Cu2+ sorption strongly depended on the sorbent type, as well as
      on initial cation concentration. The decrease in external mass transfer
      coefficients with the increase in initial metal concentrations was in excellent
      agreement with expressions based on Sherwood and Schmidt dimensionless numbers.
      The internal diffusivities through zeolite particles were in the range 1.0 x 10(
      11) to 1.0 x 10(-13) m2/min, depending on the Cu2+ concentration and the applied
      theoretical model.

PMID- 21882548
TI  - A comparative study of UV-fenton, UV-H2O2 and fenton reaction treatment of
      landfill leachate.
AB  - In this study, laboratory experiments were conducted to compare the efficacy of
      several H2O2-based advanced oxidation processes (AOPs): UV-Fenton, UV-H2O2, and
      Fenton reagent, to treat landfill leachate with the objective of removing COD and
      improving the leachate's overall biodegradability (evaluated in terms of BOD5/COD
      ratio). The results indicated that, at optimized experimental conditions of 25
      degrees C, pH 4.0, 4000 mg L(-1) H2O2, 30 mg L(-1) Fe(II) (for UV-Fenton and
      Fenton) and 60 min reaction time, the UV-Fenton system showed the highest COD
      removal. The COD removal rate in the H2O2-based AOPs was strongly dependent on
      the concentration of H2O2 and the pH value. Temperature had little effect on
      overall COD removal rate in the Fenton and Fenton-like systems. All three systems
      would result in a significant increase in the ratio of BOD5/COD, from 0.17 to
      about 0.60, at the applied H2O2 dosage of 4000 mg L(-1). The increase in
      biodegradability of the AOP leachate indicates that these AOPs would be
      beneficial for the subsequent biological treatment process. The UV-Fenton process
      was found to be the most effective approach of these H2O2-based AOPs to enhance
      the biodegradability and eliminate the colour of the leachate.

PMID- 21882549
TI  - Performance evaluation of an on-site volume reduction system with synthetic urine
      using a water transport model.
AB  - The parameters of a model of the transport of water from a wet cloth sheet to the
      air, developed for deionized water, to establish design procedures of an on-site
      volume reduction system, were identified for high salt concentrations present in
      synthetic urine. The results showed that the water penetration was affected
      neither by the salts, urea or creatinine present in the synthetic urine nor by
      the salts accumulated on the surface of the vertical gauze sheet. However, the
      saturated vapour pressure decreased, leading to reduction in the evaporation
      rate, which occurred as a result of the salts accumulating on the surface of the
      vertical gauze sheet. Furthermore, a steady-state evaporation condition was
      established, illustrating salts falling back to the tank from the vertical gauze
      sheet. Accordingly, the existing design procedure was amended by incorporating
      the calculation procedure for the saturated vapour pressure using Raoult's law.
      Subsequently, the effective evaporation area of the vertical gauze sheet was
      estimated using the amended deign procedures to assess feasibility. This
      estimation showed that the arid, tropical, temperate and cold climates are
      suitable for the operation of this system, which require requires a small place
      at household level for 80% volume reduction of 10 L of urine per day for 12
      hours' operation in the daytime.

PMID- 21882550
TI  - A preliminary study on Jatropha curcas as coagulant in wastewater treatment.
AB  - Many coagulants, mainly inorganic, are widely used in conventional water and
      wastewater treatment. Recent studies reported the occurrence of some chronic
      diseases associated with residual coagulant in treated wastewater. The use of
      alternative coagulants which are biodegradable and environmentally friendly could
      alleviate the problem associated with these diseases. This work investigates the
      capability of Jatropha curcas seed and presscake (the residue left after oil
      extraction) to reduce the turbidity of wastewater through coagulation. The
      coagulant was prepared by dissolving Jatropha curcas seed and presscake powder
      into solution. Then jar tests were conducted on kaolin solution as the model
      wastewater. The Jatropha seed was found to be an effective coagulant with more
      than 96% of turbidity removal at pH 1-3 and pH 11-12. The highest turbidity
      removal was recorded at pH 3 using a dosage of 120 mg/L. The flocs formed using
      Jatropha were observed to be bigger and to sediment faster when compared with
      flocs formed using alum. The turbidity removal was high (>98%) at all turbidities
      (100 NTU to 8000 NTU), suggesting its suitability for a wide range of industrial
      wastewater. The performance of Jatropha presscake after extraction of oil was
      also comparable to the fresh seed and alum at highly acidic and highly alkaline
      conditions. The addition of Jatropha did not significantly affect the pH of the
      kaolin samples after treatment and the sludge volume produced was less in
      comparison to alum. These results strongly support the use of Jatropha curcas
      seed and presscake as a potential coagulant agent.

PMID- 21882551
TI  - Ecological risk assessment of heavy metals from the surficial sediments of a
      shallow coastal lagoon, Egypt.
AB  - Sediment quality of Lake Maryout (one of the four Nile Delta shallow brackish
      water lakes on the south-eastern coast of the Mediterranean Sea) is of concern as
      this lake is used for land reclamation and aquaculture and is an important
      fishing source. The magnitude and ecological relevance of metal pollution in Lake
      Maryout Main Basin was investigated by applying different sediment quality
      assessment approaches. The aim of this study was to estimate ecological risk of
      trace elements (Cd, Ni, Pb, Cr, Cu and Zn) in the surficial sediments (<63 jtm
      fraction) of Lake Maryout. Heavily contaminated sediments were evaluated by the
      Sediment Quality Guideline (SQG) of the US Environmental Protection Agency. The
      degree of contamination (Cd) was estimated as very high for each site. Two sets
      of SQGs effect range-low/effect range-median values and threshold effect
      concentration (TEC) and probable effect concentration (PEC) values were used in
      this study. Sediments from each site were judged toxic when more of the PEC
      values exceeded EPA guidelines. Based on the geoaccumulation index (Ieo) of
      target trace elements, the Main Basin of Lake Maryout has to be considered as
      extremely polluted with Cd (Igeo > or =5), strongly polluted with Zn (2 < or =
      Igeo < or =3), moderately polluted with Cu (1 < or = Igeo < or = 2), unpolluted
      to moderately polluted with Cr and Pb (0 < or = Igeo < or = 1 for each) and
      unpolluted with Ni (Igeo < or = 0). Lake Maryout sediments had heavy
      accumulations of Cd, which apparently come from drains that include industrial
      and raw domestic wastes. Therefore, a sequential extraction technique was applied
      to assess the five fractions (exchangeable, metals bound to carbonate, acid
      reducible, oxidizable-organic and residual) of Cd in surface sediments. The Cd
      concentration in most sampling stations was dominated by the non-resistant
      fraction (anthropogenic). The result showed that those stations located in the
      vicinity of municipal and mixed waste drains posed a high potential risk to fauna
      and flora of Maryout Lake.

PMID- 21882552
TI  - Removal of phosphorus from water using active barriers: Al2O3 immobilized on to
      polyolefins.
AB  - Phosphorus is known to contribute to eutrophication of fresh water systems, as
      generally it is the limiting nutrient controlling algae growth. Laboratory
      studies were conducted to develop and test active barriers composed of aluminium
      oxide immobilized on to polyolefins to remove phosphorus from water. For this
      purpose, flat plates of polyethylene and polyethylene grafted with maleic
      anhydride were prepared and tested. The adsorption mechanism of phosphorus on to
      aluminium oxide was described by the Freundlich isotherm. The optimum pH interval
      for phosphorus removal was between 5.2 and 7.8, which includes the pH of natural
      waters. The maximum phosphorus removal capacity was around 11.1 microg/cm2 for
      both active barriers. Both barriers removed more than 90% of phosphorus from a
      100 mirog/L solution in a static batch experiment carried out for 90 d. The in
      situ implementation of the active barriers developed in the present study might
      be a valuable strategy to sequester phosphate and thus to control eutrophication
      in natural ecosystems, though further work is required to evaluate possible
      interferences coming from other substances present in the water.

PMID- 21882553
TI  - Distribution of the concentration of heavy metals associated with the sediment
      particles accumulated on road surfaces.
AB  - The heavy metal pollution caused by road run-off water constitutes a problem in
      urban areas. The metallic load associated with road sediment must be determined
      in order to study its impact in drainage systems and receiving waters, and to
      perfect the design of prevention systems. This paper presents data regarding the
      sediment collected on road surfaces in the city of Torrelavega (northern Spain)
      during a period of 65 days (132 samples). Two sample types were collected: vacuum
      dried samples and those swept up following vacuuming. The sediment loading (g m(
      2)), particle size distribution (63-2800 microm) and heavy metal concentrations
      were determined. The data showed that the concentration of heavy metals tends to
      increase with the reduction in the particle diameter (exponential tendency). The
      concentrations ofPb, Zn, Cu, Cr, Ni, Cd, Fe, Mn and Co in the size fraction <63
      microm were 350, 630, 124, 57, 56, 38, 3231, 374 and 51 mg kg(-1), respectively
      (average traffic density: 3800 vehicles day(-1)). By increasing the residence
      time of the sediment, the concentration increases, whereas the ratio of the
      concentration between the different size fractions decreases. The concentration
      across the road diminishes when the distance between the roadway and the sampling
      siteincreases; when the distance increases, the ratio between size fractions for
      heavy metal concentrations increases. Finally, the main sources of heavy metals
      are the particles detached by braking (brake pads) and tyre wear (rubber), and
      are associated with particle sizes <125 microm.

PMID- 21882554
TI  - Effects of nitrate reduction on the eutrophication of an urban man-made lake
      (Palacio de Cristal, Porto, Portugal).
AB  - The monitoring of phytoplankton is an important component of water quality
      assessment in artificial and natural lakes. The evolution of eutrophication in an
      urban man-made lake (Palacio de Cristal, Porto, Portugal) was followed after
      remediation measures were applied. Nutrients as well as the phytoplankton
      community were monitored and the results compared with those of a previous study.
      Sampling was done in four sites of the lake so as to assess the efficiency of NO3
      removal by the phytoplankton. The data of this study showed a reduction in NO3
      levels in the underground source water, which caused a reduction in the
      phytoplankton abundance. The nitrate removal by the phytoplankton in the lake was
      on average 51% and was much lower compared with previous studies of the same
      lake. The dominant cyanobacteria species were Pseudanabaena spp., probably due to
      the low water residence time. Monitoring of potentially toxic cyanobacteria, by
      molecular methods based on the use of toxin gene primers, will be an efficient
      early warning method. This will allow the application of corrective management
      measures before an intense toxic bloom occurs.

PMID- 21882555
TI  - Study of the scaling formation mechanism in recycling water.
AB  - To better understand the phenomenon of scaling of water that occurs in the
      cooling systems of nuclear power plants and thus to propose effective measures
      against scaling, the analysis of the scaling capacity of Salvetat mineral water
      and Seine river water was carried out in this study by the method of rapid
      controlled precipitation (RCP), which was used to estimate the scaling power of
      natural waters and to characterize the scaling formation mechanisms. The results
      showed that RCP allowed the establishment of thermodynamic conditions where the
      scaling was formed with a degree of oversaturation that much less than 40 in
      relation to a real-life scaling phenomenon. Some factors, such as the water
      composition, temperature, and initial presence or absence of calcium carbonate
      (CaCO3) nucleus, promoted or inhibited the precipitation of (CaCO3). In the water
      with a higher scaling potential, deposition on a copper surface did not occur or
      remained negligible because of the electrochemical reactions between the copper
      ions and water. The electrostatic treatment was quite good for delaying
      precipitation because it could affect the water's composition in an infinitesimal
      way.

PMID- 21882556
TI  - Advanced oxidation processes for treatment of effluents from a detergent
      industry.
AB  - Ozonation, catalytic ozonation, Fenton's and heterogeneous Fenton-like processes
      were investigated as possible pretreatments of a low biodegradable and highly
      toxic wastewater produced by a detergent industry. The presence of a Mn-Ce-O
      catalyst in ozonation enhances the biodegradability and improves the degradation
      at low pH values. However, a high content of carbonyl compounds adsorbed on the
      recovered solid indicates some limitations for real-scale application. A
      commercial Fe2O3-MnOx catalyst shows higher activity as well as higher stability
      concerning carbon adsorption, but the leaching of metals is larger than for Mn-Ce
      O. Regarding the heterogeneous Fenton-like route with an Fe-Ce-O catalyst, even
      though a high activity and stability are attained, the intermediates are less
      biodegradable than the original compounds, indicating that the resulting effluent
      cannot be conducted to an activated sludge post-treatment. The highest
      enhancement of effluent biodegradability is obtained with the classic homogeneous
      Fenton's process, with the BOD5/COD ratio increasing from 0.32 to 0.80. This
      process was scaled up and the treated effluent is now safely directed to a
      municipal wastewater treatment plant.

PMID- 21882557
TI  - Biodegradation of polyether-polyol-based polyurethane elastomeric films:
      influence of partial replacement of polyether polyol by biopolymers of renewable
      origin.
AB  - In this work we investigated the degradation process ofpolyether-polyol-based
      polyurethane (PUR) elastomeric films in the presence of a mixed thermophilic
      culture as a model of a natural bacterial consortium. The presence of PUR
      material in cultivation medium resulted in delayed but intensive growth of the
      bacterial culture. The unusually long lag phase was caused by the release of
      unreacted polyether polyol and tin catalyst from the material. The lag phase was
      significantly shortened and the biodegradability of PUR materials was enhanced by
      partial replacement (10%) of polyether polyol with biopolymers (carboxymethyl
      cellulose, hydroxyethyl cellulose, acetyl cellulose and actylated starch). The
      process of material degradation consisted of two steps. First, the materials were
      mechanically disrupted and, second, the bacterial culture was able to utilize
      abiotic degradation products, which resulted in supported bacterial growth.
      Direct utilization of PUR by the bacterial culture was observed as well, but the
      bacterial culture contributed only slightly to the total mass losses. The only
      exception was PUR material modified by acetyl cellulose. In this case, direct
      biodegradation represented the major mechanism of material decomposition.
      Moreover, PUR material modified by acetyl cellulose did not tend to undergo
      abiotic degradation. In conclusion, the modification of PUR by proper biopolymers
      is a promising strategy for reducing potential negative effects of waste PUR
      materials on the environment and enhancing their biodegradability.

PMID- 21882558
TI  - Chemical techniques for pretreating and regenerating active slag filters for
      improved phosphorus removal.
AB  - Active slag filters are an emerging technology for removing phosphorus (P) from
      wastewaters. Recent research revealed that adsorption onto Fe
      oxides/oxyhydroxides at near-neutral pH and oxidizing Eh is the key mechanism of
      P removal by melter slag filters. Currently, filter lifespan is limited by
      available adsorption sites. This study examined whether the performance and
      longevity of active filters could be improved via chemical treatment to create
      additional reactive sites as well as regenerate exhausted ones. Fresh original
      melter slag as well as slag from an exhausted full-scale filter was tested.
      Chemical reagents that could manipulate the pH/Eh of the slag granule surfaces
      and potentially activate them for further P removal were used, namely
      hydrochloric acid (HCI), sodium hydroxide (NaOH) and sodium dithionite (Na2S2O4).
      Waste stabilization pond effluent was then applied to the treated slag to assess
      the effectiveness of the treatments at improving P removal. Fresh slag treated
      with Na2S204 and HCl, respectively, retained 1.9 and 1.4 times more P from the
      effluent than the untreated fresh slag. These reagents were even more effective
      at regenerating the exhausted slag, increasing total retained P by a factor of 13
      and six, respectively, compared with untreated slag. Sodium hydroxide was
      ineffective at increasing P removal. The higher P retention by the 'treated
      exhausted slag' compared with the 'treated fresh media' indicates that adsorption
      sites on melter slag filters become increasingly reactive with time. This
      research is the first study to provide evidence that P retention by active slag
      filters can be increased by both (1) chemical pre treatment and (2) chemical post
      treatment once their P removal is exhausted, thereby potentially transforming
      them from a single use system to a more viable, reusable treatment technology.

PMID- 21882559
TI  - UV and VUV photolysis vs. UV/H2O2 and VUV/H2O2, treatment for removal of
      clofibric acid from aqueous solution.
AB  - Clofibric acid (CA), a metabolite of lipid regulators, was investigated in ultra
      pure water and sewage treatment plant (STP) effluent at 10 degrees C under UV,
      vacuum UV (VUV), UV/H2O2 and VUV/H2O2 processes. The influences of NO3-, HCO3-
      and humic acid (HA) on CA photolysis in all processes were examined. The results
      showed that all the experimental data well fitted the pseudo-first-order kinetic
      model, and the apparent rate constant (k(ap)) and half-life time (t(1/2)) were
      calculated accordingly. Direct photolysis of CA through UV irradiation was the
      main process, compared with the indirect oxidation of CA due to the slight
      generation of hydroxyl radicals dissociated from water molecules under UV
      irradiation below 200 nm monochromatic wavelength emission. In contrast, indirect
      oxidation was the main CA degradation mechanism in UV/H2O2 and VUV/H2O2, and
      VUV/H2O2 was the most effective process for CA degradation. The addition of 20 mg
      L(-1) HA could significantly inhibit CA degradation, whereas, except for UV
      irradiation, the inhibitive effects of NO3- and HCO3- (1.0 x 10(-3) and 0.1 mol
      L(-1), respectively) on CA degradation were observed in all processes, and their
      adverse effects were more significant in UV/H2O2 and VUV/H2O2 processes,
      particularly at the high NO3- and HCO3- concentrations. The degradation rate
      decreased 1.8-4.9-fold when these processes were applied to a real STP effluent
      owing to the presence of complex constituents. Of the four processes, VUV/H2O2
      was the most effective, and the CA removal efficiency reached over 99% after 40
      min in contrast to 80 min in both the UV/H2O2 and VUV processes and 240 min in
      the UV process.

PMID- 21882560
TI  - Use of Raphanus sativus L. press cake, a solid residue from biodiesel processing,
      in the production of adsorbents by microwave activation.
AB  - The objective of this study was to evaluate the performance of an adsorbent,
      based on a solid residue arising from biodiesel production, for the removal of
      cationic dyes from wastewaters. The adsorbent was produced by microwave thermal
      activation. The Freundlich model provided the best fit for equilibrium data,
      indicating heterogeneous adsorption. The adsorption capacity increased in
      comparison to the adsorbent obtained by thermal processing of the same residue in
      a conventional oven, showing that microwave processing is an attractive
      alternative for adsorbent production, given the significant reduction in
      processing time (decreased from 60 min to 3 min). Both the removal efficiency and
      the removal capacity decreased with an increase in temperature, pointing towards
      the exothermic nature of the removal process.

PMID- 21882561
TI  - Aerobic pretreatment of olive oil mill wastewater using Ralstonia eutropha.
AB  - Olive oil mill wastewater (OMW) has a high polluting power, with total phenolics
      (TP) around 2.5 g l(-1) and chemical oxygen demand (COD) 85 g l(-1). Biological
      systems offer advantages in treating this type of agro-industrial wastewater. The
      performance of phenol-adapted Ralstonia eutropha for aerobic biotreatment of OMW
      has been studied, and a TP concentration of 250 mg l(-1) found to be fully
      degraded within 24 h. This simple procedure may be adopted as a pretreatment
      prior to the normal aerobic or anaerobic techniques used for treating OMW. The
      biodegradative capability of this non-pathogenic gram-negative bacterium towards
      the TP and COD content of OMW has been evaluated. The adapted free cells were
      found able to decrease TP and COD in the undiluted OMW by 56% and 42%,
      respectively. The Monod equation was found suitable to describe the capacity of
      the cells for growing on undiluted OMW, giving micromax 0.083 per day and Ks =
      1846 mg l(-1). Using a packed-bed reactor the performance of loofa-immobilized R.
      eutropha was assessed and the reduction in TP and COD shown to be 73% and 64%,
      respectively.

PMID- 21882562
TI  - Comparison of two online flocculation monitoring techniques for predicting
      turbidity removal by granular media filtration.
AB  - Particulate matter removal in drinking water treatment via direct granular
      filtration requires specific flocculation conditions (a process typically termed
      'high energy flocculation'). Predicting filtered water turbidity based on
      flocculated water characteristics remains difficult. This study has sought to
      establish a relationship between filtered water turbidity and the flocculated
      water characteristics. Flocculation oflow-turbidity raw water was evaluated
      online using a Photometric Dispersion Analyser (PDA) and a Dynamic Particle
      Analyser in a modified jar test followed by a bench-scale anthracite filter.
      Coagulants used were alum, PASS100 and ferric sulphate, in addition to a
      polydiallyldimethylammonium chloride (polyDADMAC) cationic polymer. They were
      dosed in warm and cold waters, and flocculated with intensities (G) from 0 to 100
      s(-1). Of the two instruments selected to analyse flocculation performance, the
      Dynamic Particle Analyser was shown to be the most sensitive, detecting small
      changes in floc growth kinetics and even floc growth under low flocculation
      conditions which remained undetected by the PDA. Floc size was shown to be
      insufficient in predicting particulate matter removal by direct granular
      filtration as measured by turbidity, although a threshold d(v) value (50 microm)
      could be identified for the test conditions evaluated in this project, above
      which turbidity was systematically lower than 0.2 NTU.

PMID- 21882563
TI  - Abiotic and biotic dynamics during the initial stages of high solids switchgrass
      degradation.
AB  - An understanding of the underlying dynamics of how biotic variables drive changes
      in abiotic parameters in the early stages of biomass biodegradation is essential
      for better control of the process. Probe hybridization was used to quantitatively
      study the growth of bacteria, yeast and fungi for three levels of initial
      moisture content (60, 65 and 75% MC) over a period of 64 h. Changes in abiotic
      parameters were also documented. By 64 h, samples were significantly
      differentiated both in temporal and spatial dimension, proving that considerable
      changes had occurred in these initial stages. Maximum carbon (C) conversion
      occurred in the 75% MC reactor at a peak value of 49%, with 40% and 37% in the 65
      and 60% MC reactors, respectively. Higher temperature, higher pH, higher rates of
      O2 consumption and CO2 evolution were also observed in the highest moisture
      reactor; suggesting that of the three MCs studied, 75% MC was the optimal one for
      the process. MC during the process also proved to be important because it greatly
      influenced variation in the spatial dimension, further underscoring the
      importance of characterizing changes with bed height. Most importantly, we were
      able to positively correlate the rate of substrate degradation with bacterial
      biomass levels and highlight the critical role of bacteria in biological
      decomposition.

PMID- 21882564
TI  - Sequencing batch biofilm reactor: from support design to reactor operation.
AB  - The aim of this work was to improve the overall understanding of sequencing batch
      biofilm reactors (SBBRs) from support selection (biofilm formation) to reactor
      operation (carbon and nitrogen removal). Supports manufactured with different
      materials and geometries were tested in 2.5 L SBBRs and it was observed that
      biofilm accumulation was favoured on the supports that presented a higher
      internal surface area. The geometry of the supports and the hydrodynamic
      conditions established in the SBBRs seemed to play a more important role in
      biofilm formation than the thermodynamic interaction, expressed as free energy of
      adhesion (deltaG), between the support material and the biomass. The support that
      presented the highest biofilm accumulation per unit of surface area (DupUM) was
      used in a 28 L SBBR and it was observed that, along a typical SBBR cycle, time
      profiles of nitrogen compounds showed the typical behaviour of nitrification and
      denitrification reactions. During the fill phase (without aeration) acetate was
      simultaneously consumed in biomass growth and denitrification. Immediately after
      the beginning of the aeration phase (without influent addition), acetate was
      depleted from the liquid phase and stored as poly-beta-hydroxybutyrate that was
      later on used in the growth of biomass, owing to the high oxygen concentration in
      the reactor.

PMID- 21882565
TI  - Annual and nycthemeral studies of the survival and circulation of indicator
      bacteria in a schist aquifer.
AB  - Escherichia coli and Enterococci are widely used as indicators of faecal
      contamination of groundwater while total coliforms, which are of environmental
      but also of faecal origin, are indicators of the overall quality of the water.
      The survival of bacteria in groundwater is dependent on many factors including
      temperature, competition with indigenous bacteria and entrapment in aquifer
      material. Previous studies showed two sources of faecal contamination of a schist
      aquifer: infiltration into the ground from nearby septic tank effluents and
      seepage of landfill leachate. Water samples for bacterial analysis were collected
      from a piezometer on a monthly basis (15 months) and every six hours over two non
      consecutive days. The intermittent sampling showed relatively stable
      concentrations of bacteria over time after the removal of stagnant water.
      Therefore, a continuous bacterial contamination without significant daily
      variation exists. The ratio of E. coli densities to total coliforms densities
      (EC/TC) allowed differentiation between the sources of faecal pollution in
      groundwater by comparing the populations of faecal bacteria with those of
      environmental bacteria. Enumeration indicated that the densities of bacteria were
      much higher in this schist aquifer than those in alluvial aquifers contaminated
      by a septic tank reported in the literature.

PMID- 21882566
TI  - Characterization of atmospheric deposition and runoff water in a small suburban
      catchment.
AB  - A study has been carried out as part of the mission assigned to IRSTV (Research
      Institute of Urban Sciences and Techniques), a federative research network
      supported by the Loire Valley Region, with the objective of characterizing
      atmospheric deposition, roof runoff and street runoff in a small (31 ha) suburban
      catchment in Nantes equipped with a separate sewer system. Trace metals,
      polycyclic aromatic hydrocarbons (PAHs) and pesticides were investigated. The
      characterization of atmospheric deposition reveals a high variability of trace
      metal concentrations, which could not be explained by rainfall characteristics.
      The relative abundance order of the metals was as follows: Zn > Cu > Cr
      approximately Ni > Cd. Organic pollutants, i.e., PAHs and pesticides, were only
      rarely detected in the atmospheric deposition. Zn and Pb appear to be the major
      contaminants in runoff water, whereas the concentrations of Ni, Cu, Cr, Cd, PAHs
      and pesticides tend to remain low. On the whole, concentrations were similar to
      the lowest range reported in the literature. According to statutory thresholds,
      runoff water quality is poor because of the high Pb and Zn concentrations. Based
      on scanning electron microscopy observations, atmospheric particles do not
      apparently differ from runoff particles, with a predominance of pollen, bacteria
      and particles resulting from soil erosion. Spherical organic particles produced
      during fuel combustion have also been observed.

PMID- 21882567
TI  - Pollution profile and biodegradation characteristics of fur-suede processing
      effluents.
AB  - This study investigated the effect of stream segregation on the biodegradation
      characteristics of wastewaters generated by fur-suede processing. It was
      conducted on a plant located in an organized industrial district in Turkey. A
      detailed in-plant analysis of the process profile and the resulting pollution
      profile in terms of significant parameters indicated the characteristics of a
      strong wastewater with a maximum total COD of 4285 mg L(-1), despite the
      excessive wastewater generation of 205 m3 (ton skin)(-1). Respirometric analysis
      by model calibration yielded slow biodegradation kinetics and showed that around
      50% of the particulate organics were utilized at a rate similar to that of
      endogenous respiration. A similar analysis on the segregated wastewater streams
      suggested that biodegradation of the plant effluent is controlled largely by the
      initial washing/pickling operations. The effect of other effluent streams was not
      significant due to their relatively low contribution to the overall organic load.
      The respirometric tests showed that the biodegradation kinetics of the joint
      treatment plant influent of the district were substantially improved and
      exhibited typical levels reported for tannery wastewater, so that the inhibitory
      impact was suppressed to a great extent by dilution and mixing with effluents of
      the other plants. The chemical treatment step in the joint treatment plant
      removed the majority of the particulate organics so that 80% of the available COD
      was utilized in the oxygen uptake rate (OUR) test, a ratio quite compatible with
      the biodegradable COD fractions of tannery wastewater. Consequently, process
      kinetics and especially the hydrolysis rate appeared to be significantly
      improved.

PMID- 21882568
TI  - Contamination and chemical fractionation of heavy metals in street dust from the
      metropolitan area of Monterrey, Mexico.
AB  - The prevalence of heavy metal pollution and mobility of both Pb and Cd was
      investigated in street dust samples from the Metropolitan Area of Monterrey (MAM)
      in northern Mexico. Street dust samples from 30 selected sites were analysed for
      their content of Zn, Cd, Pb, Cr and Ni after digestion according to U.S. EPA
      Method 3051. Multivariate analysis including correlation coefficient analysis,
      Principal Component Analysis and Cluster Analysis was used to analyse the data
      and identify possible sources of these heavy metals. Compared with background
      values, elevated concentrations of Pb (300 mg kg(-1)), Cd (7.6 mg kg(-1)) and Cr
      (78 mg kg(-1)) were observed in street dust of MAM. Based on multivariate
      statistical approaches, the studied elements were classified in three main
      sources: (1) Cr, Ni and Zn mainly derived from industrial activities; (2) Cd
      originating from traffic-related activities; and (3) Pb associated with vehicular
      emissions. A sequential extraction procedure using the Tessier method was applied
      to evaluate the mobility of Pb and Cd in street dust. The majority of Pb was
      associated with the residual fraction followed by the carbonate fraction. The
      majority of Cd was associated with the residual fraction. These results indicated
      that the mobility was higher in Pb (26%) compared with Cd (11%), posing a
      potential risk to the environment.

PMID- 21882569
TI  - Intelligent failure leads to personal and professional growth.

PMID- 21882570
TI  - Politics: a natural next step for nurses.

PMID- 21882572
TI  - IOM future of nursing report recommendations are in: now what? Implications for
      nursing.

PMID- 21882571
TI  - POLST is coming to New Jersey.

PMID- 21882573
TI  - Mandated aggression management training.

PMID- 21882574
TI  - Medication error: could this be a crime?

PMID- 21882575
TI  - Indigenous health: taking the next step.

PMID- 21882576
TI  - What do you say when the end of life is close? A nurse's voice.

PMID- 21882577
TI  - Enhancing nursing practice potential: breast free flap reconstruction following
      mastectomy.
AB  - BACKGROUND: Breast cancer is the most common cancer for women in both the
      developed and the developing world, comprising nearly one quarter of all female
      cancers. The most advanced forms of treatment, including mastectomy, may produce
      a five-year survival rate of 75% or more for certain types of cancer. For women
      experiencing breast cancer, breast reconstruction is often a positive option that
      can enhance quality of life and plays a significant role in a woman's recovery
      from breast cancer. AIM: The aim of this article is to present some different
      cases of women who have undergone autologous breast reconstruction free flaps and
      discuss advanced and intensive nursing care practice. IMPLICATIONS FOR PRACTICE:
      Nurses need to not only be proficient in the postoperative physical care of
      patients who undergo mastectomy but also demonstrate advanced skills related to
      the educational needs of patients and their families and to ensure care is
      delivered in a manner that is patient centred and individualised. Nurses require
      advanced skills to meet the social and psychological care needs of the patient
      and their family during this major life event.

PMID- 21882578
TI  - Making wound care real.

PMID- 21882579
TI  - The benefits of a nurse practitioner wound outreach service.

PMID- 21882580
TI  - Electronic online infection prevention and control modules for health care
      workers.

PMID- 21882581
TI  - Copper surfaces cut hospital infection risk.

PMID- 21882582
TI  - Problem or puzzle the choice is yours.

PMID- 21882583
TI  - [The pros and cons of intravitreal drug injection].

PMID- 21882584
TI  - [Long-term outcome of radiation therapy for exudative age-related macular
      degeneration in Japan].
AB  - PURPOSE: To evaluate the long-term outcome of radiation therapy in eyes with
      exudative age-related macular degeneration (AMD). METHODS: Eighty eyes of 80
      patients (54 men and 26 women) with exudative AMD, which underwent radiation
      therapy with a photon beam of 20 Gy (2 Gy per day for 10 days) between 1998 and
      2003, were retrospectively reviewed. Average age was 69 +/- 8.1 and follow-up
      period was 66 months. Best-corrected visual acuity (BCVA), additional therapies
      and complications were assessed. RESULTS: Mean duration till the best value of
      postoperative BCVA could be reached was 10 months. The best BCVA was improved in
      20 eyes (25.0%), stabilized in 56 eyes (70.0%), and deteriorated in 4 eyes
      (5.0%). On the final visit visual improvement was observed in 9 (11.3%),
      stabilization in 25 (31.3%), and deterioration in 46 eyes (57.5%). Additional
      therapies for exudative AMD were performed in 24 eyes (30.0%). Severe subretinal
      hemorrhage was observed in 9 eyes (11.3%), which resulted in severe vision loss
      despite additional vitrectomy. CONCLUSIONS: Low-dose radiation therapy for
      exudative AMD achieved short-term efficacy but seemed less effective in the long
      term.

PMID- 21882585
TI  - [Correlation between visual field index values and mean deviation values of
      Humphrey field analyzer].
AB  - PURPOSE: We examined the correlation between the visual field index (VFI) and
      mean deviation (MD), as well as the correlation on VFI slope and MD slope.
      METHODS: This retrospective study was performed on 105 eyes of 60 patients. All
      eyes underwent examination by the Humphrey visual field analyzer. The correlation
      of the (i) VFI and MD, (ii) VFI slope and MD slope were analyzed in all eyes and
      the eyes were classified by visual field patterns (paracentral, peripheral, mixed
      and normal defect type). (iii) The agreement degree between the VFI slope and MD
      slope was examined. A generalized-estimating-equation(GEE) model and kappa
      statistic were used for analysis. RESULT: A significant correlation between MD
      and VFI was shown in all eyes, including eyes classified of visual field defect.
      The correlation between the VFI slope and MD slope was significant in all eyes.
      However, these correlations were not evident in paracentral type of defect but in
      the other types. K statistic evaluated a moderate agreement between the VFI slope
      and MD slope. CONCLUSION: A significant correlation was shown between the VFI and
      MD, VFI slope and MD slope in all eyes. However, no correlation between the VFI
      slope and MD slope existed in the paracentral area. It seems that the evaluation
      of progression of visual field defect in the central area needs to be considered
      carefully.

PMID- 21882586
TI  - [Eyelid surgery for refractory filamentary keratitis].
AB  - PURPOSE: Cases of filamentary keratitis that are unresponsive to conventional
      medical treatment methods are often encountered in the clinical setting. Here we
      report on cases of filamentary keratitis that showed no recurrence for long
      periods after performing eyelid surgery. SUBJECTS AND METHODS: Enrolled were 17
      eyes of 13 patients with filamentary keratitis who had eyelid surgery (4 men and
      9 women ranging in age from 54-89 years; mean age: 73.6 years). Ptosis operations
      were performed with blepharoptosis (14 eyes of 11 patients) and entropion
      operations were performed on cases with filamentary keratitis but without
      entropion (3 eyes of 2 patients). RESULTS: Following blepharoptosis, the
      filamentary keratitis disappeared in all cases except in one which experienced a
      recurrence of filamentary keratitis probably due to the recurrence of ptosis.
      However, the filamentary keratitis in that case also disappeared following
      reoperation for the blepharoptosis. After entropion surgery, the keratitis
      disappeared in all cases with eye drops. CONCLUSION: The satisfactory, long-term
      postoperative results obtained in this study suggest that eyelid surgery is an
      effective treatment for filamentary keratitis unresponsive to conventional
      medical treatment methods.

PMID- 21882587
TI  - [A case report of Kimura's disease causing visual dysfunction with remarkable
      eyelid swelling].
AB  - PURPOSE: We report a case of Kimura's disease involving the eyelids, presenting
      with bilateral eyelid swelling so severe that the eyelids could not be opened.
      CASE: A 37-year-old man presented with eyelid swelling and was unable to open
      both eyelids. He noted swelling and mass of bilateral eyelids since a year
      previously, and the masses enlarged gradually impairing eye-opening. Hard soft
      elastic tumors were palpated in both eyelids. Blood examination revealed marked
      peripheral blood eosinophilia and an increased serum IgE level. On T 1-weighted
      MR images, the tumors were observed as isointense masses compared to the
      extraocular muscles. On T 2-weighted images, the tumors showed hypointense
      signals while some parts were hyperintense compared to the extraocular muscles.
      On Gd-enhanced T 1-weighted images, the tumors demonstrated marked enhancement.
      The tumors in both eyelids were extirpated en bloc. Histopathology of the tumors
      demonstrated many lymphoid follicles and infiltration of large numbers of
      eosinophils and lymphocytes. Eosinophilic abscess and proliferation of blood
      capillaries were observed between the lymphoid follicles. These findings led to a
      diagnosis of Kimura's disease. PCR revealed clonal rearrangement of the T cell
      receptor gene. CONCLUSION: Kimura's disease may cause remarkable eyelid swelling
      and lead to visual dysfunction. Since recurrence of Kimura's disease is known to
      be associated with clonal rearrangement of T cell receptor genes, similar cases
      should be followed carefully for recurrence.

PMID- 21882588
TI  - [Six cases of sterile endophthalmitis developed consecutively after intravitreal
      injection of bevacizumab].
AB  - PURPOSE: To report a series of 6 cases of sterile endophthalmitis that developed
      consecutively after an intravitreal injection of bevacizumab (IVB). PATIENTS AND
      METHODS: On April 13 and 14, 2009, we performed IVB for consecutive 12 eyes of 12
      patients in a sterile condition. Within two days after injection, blurred vision
      without ocular pain, anterior chamber inflammation, and vitreous opacity were
      developed in 6 of the eyes of 6 patients. Hypopyon was not observed in any
      patient. Anterior chamber fluid from each eye and all syringes of bevacizumab
      that have been separated from the same bottle of same lot number were sent for
      bacterial culture examination. RESULTS: No bacterial colony was developed from
      the anterior chamber fluid of any of the patients nor from any of the syringes.
      Antibiotic treatment of all 6 patients was unsuccessful. The symptoms improved in
      all cases following treatment with topical corticosteroid within several days.
      CONCLUSIONS: Both the clinical course and the results of bacterial culture, lead
      to the possibility that our patients developed sterile endophthalmitis rather
      than infectious endophthalmitis. The exact causes of the endophthalmitis were not
      identified in our cases, but similar events are reported by several institutions,
      endophthalmitis following IVB needs to be considered a possibility.

PMID- 21882589
TI  - [A case of button battery-induced corneal and conjunctive burn injury and
      experimental findings of local damage].
AB  - PURPOSE: To report a case of button battery-induced alkaline burn injury of the
      cornea and conjunctiva, with experimental findings of local damage. CASE: A three
      year-old girl had a hard and polished white opacity on the nasal lower cornea and
      conjunctival injection, caused by a button battery remaining in the conjunctival
      sac for several hours. The ocular surface was washed carefully with distilled
      water. The opacity improved gradually over several months and scarring was
      replaced by secondary pterygium. EXPERIMENT: A button battery was placed on an
      eyeball of a pig, with the cathode directed toward the cornea. Corneal opacity
      developed in five minutes and increased thereafter. Another battery was sanded
      with saline-soaked gauze and the gauze near the cathode turned dark brown. This
      change intensified when the gauze was in contact with the side of the battery.
      CONCLUSIONS: The cornea and conjunctiva of the patient were damaged by continuous
      exposure to alkaline solution (concentrated NaOH) after the button battery had
      entered the lacrimal sac causing fixation by chemosis. The recent development of
      smaller batteries increases the risk of similar accidents. Button battery-induced
      burn injuries may be severe and require immediate correct diagnosis and
      treatment, especially in small children who may be difficult to examine.

PMID- 21882590
TI  - The influence of hair bleach on the ultrastructure of human hair with special
      reference to hair damage.
AB  - The influence of human hair bleaching agents with different bleaching strength on
      the ultrastructure of human hair was studied using a transmission electron
      microscope (TEM) and an energy dispersive X-ray spectrometer equipped with TEM
      (EDS-TEM). Two kinds of bleaching agents were used: a lightener agent with a weak
      bleaching effect and a powder-bleach with a stronger bleaching effect. From the
      comparison of the bleaching properties obtained by the electronic staining of
      black and white hair samples, it was suggested that the permeability of hair was
      increased by bleaching, and there was an increase of the stainability of hair
      subjected to electronic staining. The bleaching action provoked the decomposition
      of melanin granules and the flow out of granular contents into the
      intermacrofibrillar matrix. Some metal elements were detected in the melanin
      granular matrix by EDS-TEM. As a result, the diffusion of metal elements into the
      intermacrofibrillar matrix promoted further damage to the hair by catalytic
      action with the hydrogen peroxide in the bleaching agents outside the melanin
      granules. Further study will lead us to the edge of the development of a new
      bleaching agent, which reacts only with melanin granules and causes the minimum
      of damage to outside the melanin granules.

PMID- 21882591
TI  - EFTEM cytochemistry and sexual dimorphism of secretory granules in male and
      female hamster submandibular glands.
AB  - After glutaraldehyde fixation followed by osmium tetroxide postfixing, the
      secretory granules of acinar cells in male hamster submandibular glands (SGs)
      exhibit a characteristic bipartite substructure, with an electron-lucid rim and a
      more electron-dense central core. In female hamsters, the reverse is seen, with
      the larger portion of the granules forming an electron-lucid core and an outer
      electron-dense crescent rim. In the present study of endogenous peroxidase (PO)
      activity of male and female hamster SGs, secretory granules in the acinar cells
      were studied by DAB cytochemical technique. Individual granules showed bipartite
      substructure with the PO activity in a positive center core and unreacted lucid
      rim in both the male and the female acinar cells. Through isolation of granular
      fractions, the male and the female granules exhibited the same bipartite
      structure. We also examined the relation between the PO activity and
      counterstained areas in male and female hamster SGs, and the secretory granules
      of acinar cells by using EFTEM. In the male SG, the secretory granules exhibited
      the characteristic bipartite substructure to carry out parallel-EELS, nitrogen
      reflecting the presence of DAB moieties and uranium from counterstaing the
      presence the central core but not in the rim. On the other hand, the female
      bipartite secretory granules of the SG, exhibit the nitrogen reflecting the
      presence in the central core and uranium in the rim.

PMID- 21882592
TI  - Scanning electron microscopic study of the tongue in the rainbow lorikeet
      (Trichoglossus haematodus).
AB  - The dorsal lingual surfaces of rainbow lorikeet (Trichoglossus haematodus) were
      examined by scanning electron microscopy. Macroscopically, the tongue of the
      rainbow lorikeet has a finger-like shape. Three parts are distinguished in the
      dorsal surface of the tongue: the apex, body, and root of the tongue. The apex of
      the tongue has numerous processes inclined toward medial side from lateral side.
      These processes are rod-like structure and smooth surfaces. Many grooves are
      observed in both lateral sides of the lingual body. A large opening of the
      lingual gland exists in central part of the lingual root and some large openings
      of the lingual glands exist in both lateral sides of the lingual root.

PMID- 21882593
TI  - Morphology of the lingual papillae in the sitatunga.
AB  - We examined the dorsal lingual surfaces of an adult sitatunga (Tragelaphus
      spekei) by scanning electron microscopy. Filiform, fungiform and vallate papillae
      were observed. The filiform papillae consisted of a larger main papilla and
      smaller secondary papillae. The filiform papilla contained connective tissue core
      consisting of several processes. The fungiform papillae were round in shape. The
      connective tissue core of the fungiform papilla was flower-bud shaped. Lenticular
      papillae were limited on the torus lingua. The connective tissue core of the
      lenticular papilla consisted of numerous small spines, or these spines and rod
      shaped processes. The vallate papillae were flattened-oval shaped and the
      papillae were surrounded by a circular trench. The connective tissue core of the
      vallate papilla was covered with numerous small spines. These findings indicate
      that the tongue of the sitatunga is similar to that of the blackbuck and Barbary
      sheep.

PMID- 21882594
TI  - Relationship between light and dark period activity cycles and oral condition in
      senescence-accelerated mice.
AB  - We investigated the effect of tooth absence and masticatory abnormalities due to
      powdered food feeding starting during the juvenile period on light and dark
      period activity cycles in senescence-accelerated mice (SAMP1). SAMP1 were divided
      into 5 groups: Group 1, maxillo-mandibular molar tooth extraction; Group 2,
      maxillary molar tooth extraction; Group 3, mandibular molar tooth extraction;
      Group 4, powdered food; and Group 5, sham-operated control. Senescence was
      observed earliest in the powdered food group. Total 24-hour activity was higher
      in the control group than in the four other groups. In the powdered food group,
      the dark period activity decreased to less than 60% of the total activity in the
      36th week. In the tooth extraction groups (Groups 1-3), dark period activity
      decreased to less than 60% of the total activity in the 40th week. The control
      group dark period activity remained above 60% for the entire experimental period.
      Thus, the distinction between the light and dark periods disappeared earlier in
      the four experimental groups compared with the control group. Significant
      correlations were noted among total activity, degree of senescence, and percent
      dark period activity in each experimental group. Functional masticatory
      insufficiency promoted dementia and behavioral abnormalities in SAMP1.

PMID- 21882595
TI  - Double superior vena cava and anomaly of cardiovascular system with a review of
      the literature.
AB  - In a student course of gross anatomy dissection at Kanagawa Dental College in
      2008, we found an extremely rare case of the double superior vena cava that has a
      shunt between the right and left atria of a 81-year-old Japanese male cadaver.
      The left superior vena cava passed through the space between the left cardiac
      auricle and the left pulmonary vein and entered the coronary sulcus. Then it
      opened near the opening of the inferior vena cava as the coronary venous sinus to
      the right atrium. The upper edge of the interatrial septum was located at the
      site where the right superior vena cava opened to the right atrium. Accordingly,
      the right atrium connected with left atrium through this site. We discuss the
      anatomy and etiology of these anomalous structures with a brief review of the
      literature.

PMID- 21882596
TI  - [Current concepts of prognostic factors for colorectal cancer].

PMID- 21882597
TI  - [Matrix metalloproteinases: features, role in leukogenesis and prognostic
      significance].

PMID- 21882598
TI  - [Molecular markers of lymphatic and blood vessels, tumorigenesis and targets for
      blocking metastatic spreading].

PMID- 21882599
TI  - [Assay of methylated gene RARbeta2 in circulating DNA of blood from patients with
      lung cancer as a potential prognostic marker].
AB  - Blood-based methylated DNA gene RARbeta2 in circulating plasma (cir DNA) and one
      associated with blood cell surface were assayed in patients with non small cell
      lung cancer before and after combined treatment. The levels in both appeared to
      be significantly higher than in healthy subjects. Enhanced levels prior to
      treatment were associated with greater advancement of the disease and unfavorable
      prognosis (overall survival). After two courses of neoadjuvant therapy plus
      surgery methylation indices fell down to match those in healthy subjects. Our
      data may be instrumental in working out additional criteria to be used in
      diagnosis, prognosis and follow-up of patients with non small cell lung cancer.

PMID- 21882600
TI  - [Surgical and combined treatment for primary carcinoma of the trachea].
AB  - Our study was conducted in patients with primary squamous cell carcinoma of the
      trachea and adenoid cystic carcinoma (191) (radical surgery--90; combined
      treatment--101). The former pathology was relatively more aggressive. Combined
      treatment proved more effective as compared with surgery alone (5- and 10-year
      survival after surgery was 79 and 64%; combined treatment--92 and 79%,
      respectively).

PMID- 21882601
TI  - [Influence of intraoperative sodium adenosine triphosphate infusion on leukocyte
      dynamics following colonic resection in cancer patients].
AB  - The paper evaluates effects of different methods of systemic intraoperative
      anesthesia on the dynamics of leukocytes following colonic resection in tumor
      patients. Lymphocytes levels rose on day 2 after operation in patients receiving
      non-selective purine receptor agonists (sodium adenosine triphosphate) as an
      intraoperative analgesic and were significantly higher than in controls treated
      with conventional drugs (p<or=0.05).

PMID- 21882602
TI  - [Human papilloma virus and lymphatic metastasis in squamous cell carcinoma of the
      cervix].
AB  - Our study included 112 patients with squamous cell cervical carcinoma la-lib
      stages (FIGO). All of them were restaged on the basis of histological evidence
      after surgical treatment. Ninety-eight were staged at final analysis. Human
      papilloma virus (HPV) was detected in endocervical smears and paraffin blocks of
      lymph nodes by PCR and real-time PCR. Oncogenic HPV in primary tumor was detected
      in 86 (87.8%); two or more genotypes--65 (75.58%): still more--21 (24.4%). In the
      latter group, the frequency of regional lymph node metastases was significantly
      higher. HPV DNA was identified in iliac lymph nodes in 29 (26.6%); 27 of them had
      metastases to those nodes. HPV in DNA which was significantly more frequent in
      involved lymphocytes may be used as marker. Since our method for early detection
      of metastases to regional lymph nodes is highly specific, it may be recommended
      as a diagnostic procedure.

PMID- 21882603
TI  - [Value of HPV (hybrid capture 2) testing for assessing the effectiveness of
      conservative surgical treatment in CIN2-3/carcinoma in situ and microinvasive
      cervical cancer].
AB  - The prospective study in 525 patients with CIN2-3/CIS and microinvasive cervical
      cancer showed the association of epithelial lesions with HPV HR in almost all
      cases. This allowed using HPV-testing for conservative surgical treatment
      (ablation, LEEP/ LLETZ, conization) efficacy assessment and patient follow-up.
      The value of HPV-testing for residual disease and recurrence detection was higher
      that of cytology and colposcopy. HPV-testing showed 100% sensitivity and negative
      predictive value. Hybrid Capture 2 test was more useful for residual disease and
      recurrence detection than PCR, showed higher specificity (96% vs. 79,2%) and
      positive predictive value (44.8% vs. 13.4%). After conservative surgical
      treatment of CIN2-3/carcinoma in situ and microinvasive cervical cancer Hybride
      Capture 2 is to become negative thus confirming the adequacy of neoplastic tissue
      excision.

PMID- 21882604
TI  - [On ultrasound follow-up of patients after pelvic lymphadenectomy].
AB  - Ultrasound examination of the peritoneal cavity, small pelvis, iliac lymph nodes
      and femoral blood vessels (downstream of the blood flow) was performed in 346
      patients who had undergone pelvic lymphadenectomy. Post-operative lymphocele
      developed in 302 (7.2%). However, treatment was required in 98 (28.3%) only. Our
      strategy of follow-up after pelvic lymphadenectomy facilitated diagnosis and
      effective excision of lymphocele without resorting to laparotomy due to an
      improved procedure of ultrasound monitoring.

PMID- 21882605
TI  - [Potential of PET in the diagnosis and the assessment of treatment effectiveness
      in progressive malignant glioma].
AB  - Examination including MRI (CT), PET with sodium 11C-butyrate (11C-SB) and
      18fluorodeoxyglucose (18F-FDG) was carried out in 59 patients with continuing
      growth of malignant glioma. It was established that 11C-SB-PET is characterized
      by high sensitivity (94.1%) in detecting continuing growth as well as to
      differentiating it from necrosis. Our data were instrumental in prognosis and
      assaying metabolic levels in tumor (T/NT ratios) which are regarded as indices of
      accumulation (IA) of 18F-FDG-PET (FDG-IA) prior to conservative treatment. There
      were a direct correlation between metabolic activity of neoplasms and an inverse
      one with FDG-IA (r=-0.24).

PMID- 21882606
TI  - [Cancer risk in women: a possible connection with geographic and certain economic
      and social factors].
AB  - The paper deals with mulivariate regression analysis of effects of latitude,
      economic environment and electricity consumption on breast cancer morbidity in 35
      countries (1985-2007). Our data are compared with the influence of the same
      factors on incidence rates for ovarian carcinoma, endometrial and cervical cancer
      as well as those of the stomach, liver, colon and lung. It was found that rates
      of morbidity for breast, endometrial, colonic and lung cancer tend to increase
      north of the equator while cervical, gastric and hepatic cancer incidence is
      relatively higher in circumequatorial populations. In 1985, geographic factors
      made a dramatic contribution to hormone-dependent tumors incidence while economic
      ones--to that of gastrointestinal neoplasms. In the 2000-ies, climate-related
      risks of hormone-dependent tumors have gradually slumped down while those of
      economic and social factors have increased.

PMID- 21882607
TI  - [Antileukemic activity and development of resistance to cisplatin (CPT) and
      platinum (IV)-nitroxyl complex VS118].
AB  - Treatment with low doses (1/10 of LD50) of cisplatin and platinum (IV)-nitroxyl
      complex VS118 [e-ammin-d-(4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl)-a,f-bi
      s(acetate)-b,c-dichlorplatinum (IV)] was followed by a synergistic therapeutic
      effect (a 100% cure of animals) as compared with monotherapy with either drug.
      There was no synergistic increase in toxicity. The rates of resistance
      development decreased in the following order: P388/cPt+VS118, P388/cPt,
      P388/VS118. Resistant strains P388/cPt+VS18 and P388/VS118 were highly sensitive
      to doxorubicin, etoposide and cyclophoshamide. Further research in cPt+VS 118
      combinations should be continued.

PMID- 21882608
TI  - [Radical radiotherapy of primary cancer of the trachea].
AB  - The paper deals with the importance of treatment of primary cancer of the trachea
      and, in particular, the experience of the Center in using radical therapy for
      inoperable squamous cell tumors and adenoid cystic carcinoma. An original system
      of tumor staging developed at the Center draws on international classifications
      (TNIVI) and methods of radiotherapy depending on tumor localization. It is shown
      that tracheal malignancies, especially adenoid cystic carcinomas, are
      characterized by relatively high radiosensitivity.

PMID- 21882609
TI  - [Use of dicarbamin in platinum-containing chemotherapy of lung cancer].

PMID- 21882610
TI  - [Characteristics of tumor growth in patients with locally-advanced gastric
      cancer].
AB  - Locally-advanced gastric cancer features predominance of prognostically
      unfavorable histological patterns (infiltrative growth--in 87.9%, tumor grades II
      IV--69.5%). Tumor invasion into two adjacent organs or more frequently occurs in
      totally-involved stomach (65.2+/-9.7%), poorly-differentiated (grade Ill) tumors
      (44.9+/-4.5%) under-differentiated ones (grade IV) (45.9+/-8.2%). Invasion into
      one adjacent organ is significantly predominant (p<or=0.05) in tumor localized in
      the upper third of the stomach (66.2+/-5.4%); exophytic tumor growth (Borrmann I)
      (100%) and well- differentiated (grade I)--(66.7+/-21.3%).

PMID- 21882611
TI  - [Effectiveness of neoadjuvant chemoradiotherapy of locally advanced rectal cancer
      in conjunction with local hyperthermia and metronidazole].
AB  - Our study included 36 patients with hard fixed rectal tumors (T3, T4) who had
      received combined treatment at the Center's Clinics. On irrigoscopic evidence,
      lesions were more than 10 cm long. Radiotherapy was conducted thrice a week, STD
      of 4 Gy--TTD of 40 Gy; capecitabine, per os, 650 mg/m2 twice a day, days 1-22;
      oxaliplatin, 50 mg/m2, intravenously, days 3, 10 and 17; metronidazole in polymer
      composition, intrarectally, 10 mg/m2, twice, days 12 and 17 of radiotherapy;
      local hyperthermia (the <<Yakhta-4>> installation), 460 mHz, 41-45 deg. C, 60
      min, days 8, 12, 15 and 17. Diarrhea (stage III) was reported in 3 (8.3%); no
      toxicity (grade IV). Radical surgery was carried out in 35 (97.2%); sphincter
      saving operation--20 (55.5%). Therapy-related pathomorphism (grade III-IV) was
      detected in 15 (42.8%). Combined neoadjuvant chemoradiotherapy plus
      polyradiomodification featured low toxicity and good tolerability and immediate
      effect.

PMID- 21882612
TI  - [Long-term follow-up of a case of thyroid medullary carcinoma spreading to lung
      and liver].

PMID- 21882614
TI  - [Comparison of the structure of the wall of arachnoid cysts with the clinical
      course in children].

PMID- 21882613
TI  - [Influence of lighting on formation of carcinogenic N-nitrocompounds].

PMID- 21882615
TI  - [Surgical treatment of peripheral lung cancer in patients over 70 years of age:
      lobectomy or wedge resection?].

PMID- 21882616
TI  - ["Florence is dead, Agnes is dead, and we overwork as well].

PMID- 21882617
TI  - [The difficult relationship of industry and science. Money versus research].

PMID- 21882618
TI  - [Intercultural initiative "dignified life in aging". Orthodox Christians look
      forward to their own living quarters].

PMID- 21882619
TI  - [Requirements for culture sensitivity geriatric nursing. Explaining the issue as
      chief priority].

PMID- 21882620
TI  - [Culture sensitive geriatric nursing of immigrants with dementia. The heart does
      not forget].

PMID- 21882621
TI  - [Violence - (not) a topic in health care facilities, 2. Escalating spiral? -
      without me!].

PMID- 21882622
TI  - [Qualitative research: nursing diagnoses in general practice. Better quality -
      more satisfaction].

PMID- 21882623
TI  - [Klinikum am Urban organizes an interdisciplinary migration group. Multicultural
      in psychiatry].

PMID- 21882624
TI  - [Restrictive measures in long-term care. Which interventions reduce or prevent
      them?].

PMID- 21882625
TI  - [Continuous patient survey as an instrument to improve patient satisfaction: the
      relevance of nurses within the process of quality judgement].
AB  - The satisfaction of patients with their hospital stay as well as their
      willingness to recommend the clinic to friends and relatives are important
      parameters for a hospital's success. To achieve ascertained indications for
      necessary improvements concerning the quality of care, HELIOS Hospital Group has
      established a continuous patient survey. Similar to their medical quality
      management system, HELIOS puts high emphasize on transparency and benchmarks in
      order to initiate improvement processes. A critical analysis and close look
      especially on bad feedbacks of patients regarding their hospital stay allows each
      hospital, department or ward to monthly identify major drivers for critical
      responses and suggests opportunities for improvement. In the first six months of
      2009 64.741 questionaries were returned. Having analyzed them the patient survey
      showed, that nurses and medical doctors had a special influence on the patient's
      satisfaction and dissatisfaction with the hospital.

PMID- 21882626
TI  - [Sense of connection of cultural minorities: effect on leadership styles and
      acculturation pressure].

PMID- 21882627
TI  - [When MDK stands outside the door... Of errors, pitfalls and facts].

PMID- 21882628
TI  - [Practical nursing education. The future tolerates no delay].

PMID- 21882629
TI  - [The role of nursing science and research in education - a news blog facilitates
      gathering information by interested persons. "Should I now do research as
      well"?].

PMID- 21882630
TI  - [Demonstration regarding West German nursing shortage status 1989. "Florence is
      dead, Agnes is dead, and we are overworked as well].

PMID- 21882631
TI  - [Illness, accident, work disability - overview of rights and responsibilities.
      Sometimes only legal action is left].

PMID- 21882632
TI  - [Migration and nursing: in the family circle].

PMID- 21882633
TI  - [Influence of genetic mutations on clinical presentation of subretinal
      neovascularization. Report 1: The impact of CFH and IL-8 genes polymorphism].
AB  - Genetic analysis was performed in patients with subretinal neovascularization
      (CNV). The results showed significant association of CFH (compliment factor H)
      gene polymorphism with increase (rs1061170, rs514943 and rs380390) or decrease
      (rs529825, rs7524776, rs1831281, rs2274700, rs1576340, rs12144939, rs7540032) of
      CNV development risk. The incidence of IL-8 gene mutation was significantly (p =
      0.008) higher in patients after chorioretinitis. Apparently -125 > A polymorphism
      in patients with chorioretinitis increases risk of CNV development, thus
      promoting raise of proangiogenic factors concentration in eyes with inflammatory
      background. The clinical presentation in patients with AMD and myopic disease
      associated with (-125) A mutation of promoter region of IL-8 gene was similar to
      that of patients with chorioretinitis. The features are the following: focal
      pattern, no drusen and RPE detachment, predominantly classic form of CNV (without
      occult pattern), formation of well-organized newly developed vessels.

PMID- 21882634
TI  - [Influence of genetic mutations on clinical presentation of subretinal
      neovascularization. Report 2: The impact of HTRA and VEGF genes polymorphism].
AB  - A detailed analysis of influence of HTRA (serine peptidase) and VEGF (vascular
      endothelial growth factor) genes mutations is presented. The presence of one gene
      copy with allele of A- polymorphism rs1120638 of HTRA1 gen, T- polymorphism
      rs10490924 and de11443in54 of ARMS2 gene increases the risk of CNV in patients
      with AMD. The feature of clinical presentation in patients with CNV associated
      with (-625) A mutation of promoter region of HTRA1 gene in two chromosomes was
      fulminant course of the disease from exudative to scarring processes with fibrous
      tissue formation not just with sub-, but also intra- and preretinal localization.
      Genetic screening showed that combination of studied mutations (402H, (-625) A
      and (-251) A in both gene copies of CFH, HTRA and IL-8) results in the most
      severe and rapidly progressing form of the disease. Two new mutations were
      revealed in promoter region of VEGF gene: G > A replacement in position of (-72)
      nucleotide from transcription start and G > A replacement in 5'-nontranslated
      region of the 1st gene exon in position of (+31) nucleotide from transcription
      start.

PMID- 21882635
TI  - [Normal and pathological structural features of lacrimal gland based on spatial
      ultrasound digital examination].
AB  - For the first time vital morphological structure of lacrimal gland was
      investigated based on spatial ultrasound digital examination. Structural
      characteristics of lacrimal gland are described considering anatomic topography
      and blood supply. These characteristics are analyzed based on planar and
      volumetric sonography depending on the patient age and pattern of changes. Their
      correlation is studied. The results of lacrimal gland examination allowed us to
      analyze a number of ultrasound diagnostic signs and compare them with changes in
      acute dacryoadenitis, MALT-lymphoma, Sjogren disease, sarcoidosis and thyroid eye
      disease. Revealed features may be useful for understanding of nature of clinical
      presentation. The results of the study may help to interpret diagnostic signs and
      follow up their evolution in a clinical course of a disease.

PMID- 21882636
TI  - [Complex ultrasound examination children with persisting hyperplastic primary
      vitreous].
AB  - Complex ultrasound examination was performed in 108 children with unilateral
      congenital cataract (UCC) and persisting hyperplastic primary vitreous syndrome
      (PHPVS) to reveal indications and contraindications for surgery. The presence of
      functioning vessels with linear blood flow velocity (LBFV) measurement was
      performed in fibrovascular band and retrolenticular membrane (RLM) in different
      stages of PHPVS using color Doppler and energetic mapping. The echographic
      density of fibrovascular band and RLM was estimated using echodensitometry. The
      results of the study showed correlation of PHPVS severity and fibrovascular band
      diameter, LBFV in the vessels of the band and echographic density of the band,
      RLM and their thickness as well.

PMID- 21882637
TI  - [Potential of ultrasound biomicroscopy in diagnosis of ocular trauma with
      intraocular metallic foreign bodies].
AB  - A detailed analysis of ultrasound biomicroscopy (UBM) scanogramms of 4 patients
      with a history of trauma and signs of metallosis is performed. In all cases
      foreign body was found and its precise localization in relation to anterior
      segment structures was identified. The following changes were revealed and
      described: pathological changes of cornea, lens and its fibers, uveal tract in
      silent zone, zone of retinal periphery and secondary vitreous changes due to
      trauma itself and chemically active foreign body invasion and long persistence.
      UBM is recommended to be the part of examination algorithm in patients with
      penetrating ocular trauma and screening of latent metallosis.

PMID- 21882638
TI  - [Potential of ultrasound biomicroscopy of retinal periphery in cataract of
      different etiology].
AB  - Presence and pattern of peripheral retinal changes were studied using ultrasound
      biomicroscopy (UBM) in patients with cataract of different etiology. UBM was
      performed in 85 eyes of 65 patients. Mean age was 65, 75+8, 19 years old. UBM was
      performed using "Sonomed" equipment (USA). Morphology of revealed by means of UBM
      peripheral retinal changes was made in 5 eyes with uveal melanoma. The signs of
      retinoschisis were found in 82 eyes (96.5%) using UBM. The initial UBM signs
      represent inclusions in the inner retinal layers. With the progressing of schisis
      cystic splitting of retina was found. Confluence of distinct cysts into one
      schisis zone was characteristic for further progressing. Thus peripheral
      retinoschisis has acoustic stages, that are confirmed morphologicaly and can be
      revealed by means of UBM in the majority of old patients with cataract of
      different etiology.

PMID- 21882639
TI  - [Digital X-ray examination in diagnosis of lacrimal pathways disorders].
AB  - Digital radiological images of normal and patients with lacrimal pathways
      disorders were analyzed. Potentials of digital X-ray in diagnosis of lacrimal
      pathways disorders are demonstrated.

PMID- 21882640
TI  - [Efficacy of valve drainage devices in secondary glaucoma in patients with
      artificial iridolenticular diaphragm].
AB  - Results of 5 Akhmed valve implantations in patients with secondary glaucoma
      various time after artificial iridolenticular diaphragm implantation after
      concomitant iris and lens trauma were analyzed. Surgery allowed to achieve
      reliable IOP decrease when severe scar deformation of drainage zone of the
      anterior chamber prevents traditional hipotensive procedures because of their
      ineffectiveness. Besides visual acuity stabilization a safe performance of
      subsequent reconstructive procedures can become possible as well.

PMID- 21882641
TI  - [The value of anterior stromal puncture in the treatment of bullous keratopathy].
AB  - Results of anterior stromal puncture (ASP) in treatment of painful bullous
      keratopathy (PBK) are presented and its mechanism of action is hypothesized. ASP
      is an effective, simple, safe and low-cost procedure for symptomatic relief in
      patients with PBK.

PMID- 21882642
TI  - [Comparative experimental morphological study of efficacy and safety of near
      infrared and visible wave-length laser iridoplasty].
AB  - The features of interaction of laser radiation with iris tissue were determined
      in experimental morphological study. The potential of laser irradiation with
      different spectral characteristics for pupil ectopia correction is estimated. The
      results of morphometry showed effectiveness of near-infrared diode laser
      radiation, that presents as an iris contraction in coagulation region with
      minimal tissue trauma. This fact allows us to propose a near-infrared diode laser
      radiation as a treatment option for correction of pupil form and location.
      Alternatively visible wave-length laser showed to be less effective and more
      traumatic.

PMID- 21882643
TI  - [Possible complications of orthokeratology in myopia correction].
AB  - Clinical cases representing complications (refractive, infectious and trophic) of
      orthokeratologic lenses (OKL) use are described. These clinical cases show that
      complications of OKL use can be both similar to those of routine contact
      correction and caused by features of mechanism of corneal refraction change as a
      result of OKL wear. In our opinion efficacy and safety of this option is directly
      depends on the correct lens fitting, patient's compliance and regular monitoring
      of corneal changes.

PMID- 21882644
TI  - [An experience of dried cornea transplantation].
AB  - Sometimes an urgent lamellar keratoplasty remains the only treatment option for
      corneal defect closure. When fresh donor tissue is absent as it is regular in
      recent years dried cornea transplantation becomes reasonable. In recent years in
      ocular trauma department 320 transplantations of dried on silicagel cornea were
      performed. Analysis of results allows to conclude that use of dried cornea is a
      promising surgical procedure to preserve the globe and in some cases to prepare
      the eye with severe trauma for subsequent optic surgery.

PMID- 21882645
TI  - [Options for intraocular pressure measurement in patients with corneal
      disorders].
AB  - Intraocular pressure was estimated in patients with corneal disorders and
      secondary glaucoma. 25 patients (29 eyes) with complicated corneal opacities and
      secondary glaucoma were included into the study. In these patients the most
      reliable results were revealed using bidirectional corneal applanation (ORA) with
      contact lens on a cornea. If ORA is not available tonometer TGDc01-diaton should
      be used.

PMID- 21882646
TI  - Supplemental UV-B radiation induced changes in growth, pigments and antioxidant
      pool of bean (Dolichos lablab) under field conditions.
AB  - Present study is conducted to evaluate the response of bean (Dolichos lablabcv .
      pusa early prolific) plants to supplemental UV-B (sUV-B: 280-315 nm: 7.2 kJ m(-2)
      d(-1)) radiation. UV-B caused alteration in biomass translocation pattern with
      more retention of biomass in below ground parts leading to an increment in root
      shoot ratio. Specific leaf area (SLA) which is the measure of leaf thinness,
      increased in plants under sUV-B exposure by 95.7 and 82.3% after 15 and 30 days
      after germination. Photosynthetic machinery of bean plants was the potential
      target of UV-B as photosynthetic rate was decreased by 88.6% at 30 days after
      germination. sUV-B lead to the formation of reactive oxygen species thus
      generating oxidative stress. Stimulation of antioxidant defense system (enzymatic
      and non-enzymatic) was observed due to sUV-B radiation. Phenolic content
      decreased (34.7 and 18.6%) but protein showed varied response, increased
      initially (34%) thereafter declined (10.2%) under sUV-B radiation.

PMID- 21882647
TI  - Life history of a free-living marine nematode Daptonema normandicum reared in
      laboratory.
AB  - Life history of a free-living meiobenthic nematode Daptonema normandicum (DeMan,
      1890) was studied in the laboratory. Live specimens were primarily collected from
      the sewage outlet site near the mouth of the Mandovi estuary, Goa This species
      was the most dominant (> 67%) among the meiobenthic nematodes. Vertically,
      nematode abundance was highest at the surface sediment and correlated with the
      organic carbon and sediment chlorophyll-a. Considering their dominance in the
      meiofauna, attempts were made to rear D. normandicum in laboratory. Salinity of
      the culture medium was maintained at 14 to 17 PSU (same as the collection site).
      All the culture experiments were conducted in semisolid nutrient agar media at 27
      +/- 2 degrees C temperature for 12 hr dark: 12 hr light conditions. The food
      consists primarily of an unidentified bacterium and mixed algae, but diatom and
      ciliates were also observed in culture. Females produced first batch of eggs at
      the age of 23 days. Gravid female normally carry 8-10 eggs. Embryonic development
      is completed in -72 hr and entire life cycle (egg to adult) was completed in 22
      24 days. Average size of juveniles at the hatching was 0.189 mm. Young
      individuals attains a maximum size of 1.23 mm (male) and 1.04 mm (female) in -21
      23 days. Growth, in terms of length was augmented upto 23rd day and ceased
      thereafter. The daily growth increment for the first 5 days was 0.01-0.04 mm
      which increased upto 0.05-0.08 mm d(-1) during the maturation (10-18 days). Male
      : female ratio was 1:2. In this laboratory study, we provided information on the
      embryonic development, the life cycle and ecology Our results demonstrated that
      D. normandicum can be reared successfully under the controlled conditions,
      suggesting possible use of this species in toxicological and aquaculture studies.
      The culture method described is very handy and can be applicable for rearing
      other meiobenthic species particularly the nematodes with comparable feeding
      habits.

PMID- 21882648
TI  - Seasonal variations in abundance of nitrifying bacteria in fish pond ecosystem.
AB  - Seasonal changes in abundance of nitrifiers (ammonia-oxidizing and nitrite
      oxidizing bacteria) in surface and bottom water of freshwater ponds were examined
      with respect to temperature, DO, pH as well as concentration of ammonia and
      nitrite. The most probable number (MPN) of ammonia-oxidizers in different ponds
      varied from 1297 +/- 3.6 to 1673.23 +/- 0.36 ml(-1) in bottom and 720.5 +/- 8.1
      to 955.3 +/- 10.8 ml(-1) in surface water during the rainy season while the MPN
      ranged from 1074 +/- 1.07 to 1372.17 +/- 4.6 ml(-1) in bottom and 515 +/- 10.1 to
      678 +/- 11.8 ml(-1) in surface water in winter. However, the MPN were greatly
      reduced in summer and ranged from 435.05 +/- 15.7 to 547.54 +/- 2.12 ml(-1) in
      bottom and 218.7 +/- 7.3 to 368.4 +/- 9.32 ml(-1) in surface water. Similar
      seasonal trends were also observed in MPN of nitrite-oxidizers. Among all the
      physico-chemical parameters, abundance of nitrifiers was more positively
      correlated with ammonia and nitrite concentration in all the seasons. The
      abundance of nitrifiers in surface and bottom water was highest in rainy season
      followed by winter and modest in summer. The potential nitrification activities
      and oxidation rates were shown to be linear and activity of ammonia-oxidizing and
      nitrite-oxidizing bacteria was highest during rainy season.

PMID- 21882649
TI  - Lytic bacteriophages specific to Flavobacterium columnare rescue catfish, Clarias
      batrachus (Linn.) from columnaris disease.
AB  - This investigation was aimed to find out appropriate strategy against antibiotic
      resistant bacterial fish pathogen, F. columnare. This pathogen was found
      persistently associated with fishes causing columnaris disease and ensuing mass
      mortality in hatchery and culture system of Sub - Himalayan region. Nine lytic F.
      columnare phages (FCP1 - FCP9) specific to its fifteen isolates were isolated
      from the water and bottom sediments of various geo-climatic regions of North
      India. The F. columnare phage FCP1 (made of hexagonal head and non contractile
      long tail belonging to family Podovariedae, a member of DNA virus) exhibited
      broader host range to lyse 9 out of 15 isolates of F. columnare. Therapeutic
      ability of FCP1 phage was assessed in C. batrachus inoculated intramuscularly
      (im) with virulent bacterial isolate FC8 and post inoculated (PI) with FCP1 phage
      (@ 10(8) : 10(6):: cfu : pfu) through intramuscular (im), immersion (bath) and
      oral (phage impregnated feed) treatment. Significant (p < 0.001) reduction (less
      than 10(-3) cfu ml(-1)) in host bacterium in the sera, gill, liver and kidney of
      challenged fishes was noted after 6 hr of phage treatment. Quantum of phage
      played a significant role in bringing down bacterial population as in the sera of
      dose 1 (@ 4.55 x 10(6) pfu ml(-1)) and dose 2 (@ 9.15 x 10(6) pfu ml(-1)) treated
      fishes mean log10 cfu value reduced by 3 logs (58.39%) and 5 logs (73.77%) at 96
      hr, respectively. Phage treatment led to disappearance of gross symptoms,
      negative bacteriological test, detectable phage and 100% survival in
      experimentally infected C. batrachus. Result of this study provides evidence of
      profound lytic impact of FCP1 phage and represents its interesting therapeutic
      importance against antibiotic resistant F. columnare.

PMID- 21882650
TI  - Methane emission from rice fields in relation to management of irrigation water.
AB  - A field experiment was conducted for two years to find out best water management
      practice to mitigate methane emission from the rice-fields. Continuously flooded
      conditions yielded two major flushes of methane emission and on an average
      resulted in relatively higher rate of methane emission (2.20 and 1.30 mg m(-2)
      hr(-1), respectively in 2005 and 2006) during the kharif season. The methane flux
      was reduced to half (1.02 and 0.47 mg m(-2) hr(-1), respectively in 2005 and
      2006) when rice fields were irrigated 2-3 days after infiltration of flood water
      into the soil. Irrigating the field at 0.15 bar matric potential reduced seasonal
      methane flux by 60% (0.99 and 0.41 mg m(-2) hr(-1), respectively in 2005 and
      2006) as compared to completely flooded conditions, without any decline in grain
      yield (60 q ha(-1)).

PMID- 21882651
TI  - Drought induced changes in growth, leaf gas exchange and biomass production in
      Albizia lebbeck and Cassia siamea seedlings.
AB  - Diurnal trends in net photosynthesis rate (P(N)), stomatal conductance (g(s)),
      water use efficiency (WUE) and biomass were compared in six-month-old seedlings
      of Albizia lebbeck and Cassia siamea, under different levels of drought stress.
      The potted plants were subjected to four varying drought treatment by withholding
      watering for 7 (D1), 14(D2) and 25 (D3) days. The fourth group (C) was watered
      daily and treated as unstressed (control). Species differed significantly (p <
      0.001) in their physiological performance under varying stress conditions. Higher
      P(N) of 11.6 +/- 0.05 in control followed by 4.35 +/- 0.4 in D1 and 2.83 +/- 0.18
      micromol m(-2) s(-1) in D2 was observed in A. lebbeck. A significant (p < 0.001)
      reduction in P(N) was observed in C. siamea (C 7.65 +/- 0.5 micromol m(-2) s(-1),
      D1, 2.56 +/- 0.33 micromol m(-2) s(-1) and D2, 1.4 +/- 0.01 micromol m(-2) s(-1))
      at 9 hr. A positive correlation was seen between P(N) and g(s) (A. lebbeck, r2 =
      0.84; C. siamea, r2 = 0.82). Higher WUE was observed in C. siamea (D2, 7.1 +/-
      0.18 micromol m(-2) s(-1); D3, 8.39 +/- 0.11 micromol m(-2) s(-1)) than A.
      lebbeck, (control, 7.58 +/- 0.3 micromol m(-2) s(-1) and D3, 8.12 +/- 0.15
      micromol m(-2) s(-1)). The chlorophyll and relative water content (RWC) was more
      in A. lebbeck than C. siamea. Maximum biomass was produced by A. lebbeckthan C.
      siamea. From the study, one could conclude that A. lebbeckis better than C.
      siamea in adopting suitable resource management strategy and be best suited for
      the plantation programs in the semi-arid dry lands.

PMID- 21882652
TI  - Effect of caffeine, norfloxacin and nimesulide on heartbeat and VEGF expression
      of zebrafish larvae.
AB  - The use of pharmaceuticals during pregnancy may causes abnormalities to the
      embryo. Sometime the drug also effect to the new born if the drug transferred
      through lactation. We have used zebrafish model to see the effect of some
      pharmaceuticals on embryos and larvae. Three drugs, caffeine, norfloxacin and
      nimesulide, were used for this study to see the effect mainly the hatching rate
      of eggs, heart beat rate and the vascular endothelial growth factor (VEGF)
      expression of the larvae. VEGF is an important signaling protein that involved
      generating the new blood vessels during embryonic development. We have used 10,
      20, 50, 100 microg ml(-1) concentrations of all the drugs to see the effect. No
      significant mortality or malformations were observed in zebrafish embryos.
      Hatching was stared from 60 hr. In control group, 91% hatching rate was observed.
      Lowest hatching rate was observed using highest concentration of norfloxacin (100
      microg ml(-1)) and nimesulide (100 microg ml(-1)) i.e. 55 and 56% respectively.
      In control group, 110 to 115 heart beat rate was counted per minute.
      Significantly higher heart beat was observed in caffeine treated group which is
      125 to 140 min(-1) Lower heart beat was noted in nimesulide treated group which
      is 100 min(-1). We have tried to observe the possible effect of VEGF of the
      larvae by these three drugs. Expression of VEGF was very low in caffeine treated
      group. Almost no VGF expression was observe in 100 microg ml(-1) caffeine treated
      group. These studies suggest that there is a possibility that high dosage of
      caffeine can harm the unborn baby or new born babies, if the mothers use
      caffeine.

PMID- 21882653
TI  - Impact of paper mill effluent on growth and development of certain agricultural
      crops.
AB  - The physico-chemical characteristics of paper mill industry effluent were
      measured and some were found to be above the permissible limits prescribed by
      Indian irrigation water standard. A study was conducted in pots to investigate
      the effects of different concentrations (10, 20, 30, 40, 50, 60, 70, 80 and 100%)
      of paper mill effluent on growth and production of rice, mustard and peafor three
      years. The study reveals that the paper mill effluent has deleterious effect on
      the growth of crop at higher concentrations. However, at lower concentration
      (viz. 10 to 40% in rice, 10 to 50% in mustard and 10 to 60% in pea) of effluent,
      beneficial impact on general welfare of the crops was noticed. Growth and
      development was increased with increasing the concentration of the effluent up to
      30% in rice, 40% in mustard and 50% in pea. Investigation showed that the growth
      and production of rice, mustard and pea was found maximum at a concentration of
      30, 40 and 50% effluent respectively.

PMID- 21882654
TI  - Comparative studies on morphological and biochemical characters of chickpea
      genotypes under chilling stress.
AB  - Comparison of chickpea (Cicer arietinum L.) genotypes for morphological and
      biochemical attributes was done. Morphological characters viz. Plant height,
      number of branches and number of leaves were recorded highest in chilling
      tolerant genotypes at early stages of development (30 and 60 DAS) whereas at
      later stages (90 and 120 DAS) these characters were recorded highest in chilling
      sensitive genotypes. Pollen viability percentage at 5 and 10 degrees C
      temperatures were recorded highest in chilling tolerant genotypes as compared to
      sensitive genotypes. Biochemical characters viz. electrolyte leakage (%), total
      soluble sugars and total free amino acids were recorded highest in chilling
      tolerant genotypes as compared to sensitive genotypes.

PMID- 21882655
TI  - Determination of atmospheric heavy metals using two lichen species in Katni and
      Rewa cities, India.
AB  - A biomonitoring study was conducted to assess the levels of atmospheric heavy
      metal pollution in Katni and Rewa cities of Madhya Pradesh, state in central
      India. The Pyxine cocoes and Phaeophyscia hispidula, two epiphytic foliose lichen
      were used as bioindicators in the present study and seven metals (As, Al, Cd, Cr,
      Fe, Zn, Pb) were analyzed in naturally growing thallus. The concentrations of
      these metals was observed to be in higher range as maximum values of Al, Cd, Cr
      and Zn were reported from the lichen samples from Rewa city which was 561.8 +/-
      2.4, 6.8 +/- 0.8, 35.2 +/- 1.4, 214.6 +/- 2.0 microg g(-1) dry weight
      respectively. Whereas As, Fe and Pb were reported maximum in the lichen samples
      collected from Katni city areas with 33.4 +/- 0.05, 689.4 +/- 2.6, 13.3 +/- 0.5
      microg g(-1) dry weight respectively. However the accumulation of Cd and Pb from
      both the cities are more or less similar in concentration. The selectivity
      sequence of metals were Fe>Al>Zn>As>Cr>Pb>Cd in Katni city, and
      Al>Fe>Zn>Cr>As>Pb>Cd in Rewa city. The findings of this study indicates that
      extent of heavy metal pollution in the atmosphere of the two cities which may
      lead to adverse health affects.

PMID- 21882656
TI  - Diversity and community structure of butterfly of Arignar Anna Zoological Park,
      Chennai, Tamil Nadu.
AB  - Investigation was carried out on the diversity of butterfly fauna in selected
      localities of conservation and breeding center of Arignar Anna Zoological Park
      (AAZP), Chennai, Tamil Nadu. Atotal of 56 species were recorded, 15 of them
      belonged to Pieridae, 12 Nymphalidae, 9 Satyridae, 8 Papilionidae, 7 Danaidae, 3
      Lycaenidae and 1 species each belonged to the families Acraeidae and Hesperidae.
      Qualitatively and quantitatively Pieridae family were comparatively dominant than
      that of other families. The notable addition to the 25 more species listed during
      this observation were compared to previous field survey. Comparison of butterfly
      species distribution between the different localities revealed that butterfly
      species richness was higher at mountain region with 52 species and lowest of 25
      species at public visiting areas. Visitor's activities may be that reason for
      effects on butterfly distribution and lack of vegetation. Each five endemic and
      protected species (i.e. endangered) listed under the Wildlife (Protection)Act
      were highlighted greater conservation importances of the AAZP. It is suggest that
      butterfly species diversity generally increase with increase in vegetation and
      declines with the increase in disturbance.

PMID- 21882657
TI  - Effect of marble dust on plants around Vishwakarma Industrial Area (VKIA) in
      Jaipur, India.
AB  - The paper describes the effect of marble dust on plants in and around Vishwakarma
      Industrial Area (VKIA) Jaipur, Rajasthan (India). Trees species growing in and
      around VKIA area were selected and various morphological characteristics were
      studied such as leaf area dry weight ratio (LADWR), Dust retaining capacity (DRC)
      and Chlorophyll content. In the study the effects of marble dust on selected tree
      species was observed. LADWR was recorded maximunm 217.90 cm2 g(-1) dry wt. in
      Polyalthia longifolia in VKIA and minimum 98.74 cm2 g(-1) dry wt. in Ficus
      religiosa in Nindar whereas The DRC was observed maximum 178.51 mg cm(-2) in
      Azadirachta indica in VKIA as well as minimum recorded 66.41 mg cm(-2) in
      Thevetie pervvianain in Vidyadher Nagar. However the Total Chlorophyll Content
      was also determined and it was found maximum in Bougainvillea i.e. 2.949 mg g(-1)
      (fresh wt.) in VKIA whereas minimum for Nindar i.e. 0.784 mg g(-1) (fresh wt.) in
      Ficus religiosa.

PMID- 21882658
TI  - Marine ecological habitat: a case study on projected thermal power plant around
      Dharamtar Creek, India.
AB  - Estuaries and tidal creeks, harboring mangroves particularly, face tremendous
      anthropogenic pressures. Expansion of mega cities and the thermal power plants
      are generally proposed in the vicinity of estuaries and creek, due to the
      feasibility of intake and discharge of water for cooling. Discharges from such
      developments remain constant threat of increasing thermal pollution and affecting
      the quality of environment. The baseline information on prevailing quality of
      aquatic environment comes handy for understanding alterations due to such
      activities. Principle component analysis (PCA) revealed that temperature, pH,
      salinity, suspended solids, DO, BOD and phaeophytins are major parameters
      influencing the creek system. Heated effluents may have direct and adverse
      impacts on these parameters, altering biotic constituents. Hence, periodic and
      detailed observations are necessary to estimate exact response of biotic
      communities to changing environment. The present paper is based on case study,
      projecting a power plant in the vicinity of major mangrove habitats of Dharamtar
      creek.

PMID- 21882659
TI  - Selection of facility location under environmental damage priority and using
      ELECTRE method.
AB  - In the recent years, the environmental problems have reached to a vital extent,
      which is pushing the boundaries and far beyond daily evaluations. Industrial
      plants, the energy sources and uncontrolled release of pollutant gases (SO2, CO2
      etc.) in the production stage have the greatest share in the occurrence of
      unfavorable environmental conditions. For this reason, the dimension of the
      problems that may arise in the production stage of industrial plants is directly
      related to the selection of facility location. In this study, geographical
      regions (a total of 7 regions) of our country have been analyzed in terms of
      environmental values based on their basins and the unfavorable environmental
      problems that are currently being experienced. Considered as such, with the
      directives of an expert group composed of nature scientists, the criteria and
      alternative areas are determined using the data gathered on ecosystem, basin
      characteristics, and land types. Since the primary goal is to keep the
      environmental damages at the minimum level, comprehensive definition of the
      problem is constructed by consultation of the expert group and the criteria are
      determined. Considering the fact that it will prevent the drawbacks generated by
      making decisions depending on certain stereotypes toa great extent, ELECTRE
      (Elimination and Choice Translating Reality English - Elimination Et Choix
      Traduisant la Realite) method is used to determine in which geographic region our
      country's industrial plants should be located.

PMID- 21882660
TI  - Shift in nutrient and plankton community in eutrophic lake following introduction
      of a freshwater bivalve.
AB  - The impact of the freshwater bivalve Corbicula leana on plankton community
      dynamics was examined during a cyanobacterial bloom period. Nutrient and
      chlorophyll concentrations, primary productivity, and phytoplankton and
      zooplankton communities in the experimental enclosures were measured at 2-3 day
      intervals. The introduction of mussels reduced net primary productivity and
      phytoplankton and chlorophyll. Chlorophyll decreased immediately following
      addition of 100 mussels and then increased over time. After 600 mussels were
      added, chlorophyll decreased continuously from 87to 25 microg l(-1), approaching
      that in the mussel-free enclosure. Simultaneously, water transparency increased
      and concentrations of suspended solids and total phosphorus decreased. Mussel
      addition caused short-term increases in nutrient concentrations, especially
      following high-density treatment: phytoplankton density decreased, while cell
      density in the mussel-free enclosure increased. Zooplankton densities in the two
      enclosures were similar; however, carbon biomass in the mussel enclosure
      increased, associated with an increase in large zooplankton. The trophic
      relationship between phytoplankton and zooplankton was positive in the mussel
      free enclosure and negative in the mussel-treatment enclosure, possibly
      reflecting effects of mussels on both consumer and resource control in the
      plankton community. Thus, filter feeding by Corbicula affects nutrient recycling
      and plankton community structure in a freshwater ecosystem through direct feeding
      and competition for food resources.

PMID- 21882661
TI  - Combined effect of iron and zinc on micronutrient levels in wheat (Triticum
      aestivum L.).
AB  - A nutrient solution experiment was conducted to investigate the effect of Fe and
      Zn supply on Fe, Zn, Cu, and Mn concentrations in wheat plants. The experiment
      used a factorial combination of two Fe levels (0 and 5 mg l(-1)) and three Zn
      levels (0, 0.1 and 10 mg I(-1)). The supply of Fe (5 mg l(-1)) and Zn (0.1 mg l(
      1)) increased plant dry weight and leaf chlorophyll content compared to the Fe or
      Zn deficient (0 mg 11) treatments. However, excess Zn supply (10 mg l(-1))
      reduced plant dry weights and leaf chlorophyll content. Iron supply (5 mg l(-1))
      reduced wheat Zn concentrations by 49%, Cu concentrations by 34%, and Mn by 56%
      respectively. Zinc supply (10 mg l(-1)) reduced wheat Fe concentrations by an
      average of 8%, but had no significant effect on Cu and Mn concentrations.
      Stepwise regression analyses indicated that Zn, Cu, and Mn concentrations were
      negatively correlated with root- and leaf-Fe concentrations, but positively
      correlated with stem-Fe concentrations. Leaf-Mn concentrations were negatively
      correlated with root-, stem- and leaf-Zn concentrations.

PMID- 21882663
TI  - Studies on antimicrobial activities of solvent extracts of different spices.
AB  - The antimicrobial activities of the ethyl acetate, acetone and methanol extract
      of 12 plant species were studied. The extract of Capsicum annuum (red pepper)
      (fruit) Zingiber officinale (ginger) (root), Cuminum cyminum (cumin), Alpinia
      ficinarum (galingale), Coriandrum sativum (coriander), Cinnamomun zeylanicum Nees
      (cinnamomun), Origanum onites L. (thyme), Folium sennae (senna), Eugenia
      caryophyllata (cloves), Flos tiliae (lime), Folium menthae crispae (peppermint)
      and Piper nigrum (blackpepper) were tested in vitro against 2 fungi and 8
      bacterial species by the disc diffusion method. Klebsiella pneumonia 13883,
      Bacillus megaterium NRS, Pseudomonas aeroginosa ATCC 27859, Staphylococcus aureus
      6538 P, Escherichia coil ATCC 8739, Enterobacter cloaca ATCC 13047,
      Corynebacterium xerosis UC 9165, Streptococcus faecalis DC 74, Kluyveromyces
      marxianus, Rhodotorula rubra were used in this investigation. The results
      indicated that extracts of different spices has shown antibacterial activity in
      the range of 7-24 mm 30 microl(-1) inhibition zone Eugenia caryophyllata (clove),
      7-20 mm 30microl(-1) inhibition zone Capsicum annum (red pepper) and Cinnamomun
      zeylanicum (cinnamon) bark, 7-18 mm 30microl(-1) inhibition zone Folium sennae
      (senna) leaves, 7-16 mm 30 microl(-1) inhibition zone Zingiber officinale
      (ginger) root, 7-15 mm 30microl(-1) inhibition zone Cuminum cyminum (cumin) seed,
      7-14 mm 30 microl(-1) inhibition zone Folium menthae crispae (peppermint),
      Origanum onites (thyme) leaves and Alpinia ficinarum (galingale) root, 7-12 mm 30
      microl(-1) inhibiton zone Piper nigrum (blackpepper), 7-11 mm 30microl(-1)
      inhibition zone Flos tiliae (lime) leaves, 7-8 mm 30microl(-1) inhibition zone
      Coriandrum sativum (coriander) to the microorganisms tested.

PMID- 21882662
TI  - Characterization in the archaeological excavation site of heterotrophic bacteria
      and fungi of deteriorated wall painting of Herculaneum in Italy.
AB  - Microbiological characterization of frescos in four different locations (Collegio
      degli Augustali, Casa del Colonnato Tuscanico, Casa dello Scheletro and Casa del
      Gran Portale) of excavation sites of Herculaneum was carried out. The use of
      infrared thermography allowed detecting sample points on frescos with greatest
      moisture not visible to the naked eye, resulting in structural damage. The
      microclimatic conditions provided perfect habitat for bacteria and fungi,
      particularly of spore forming and mould. In fact, heterotrophic bacteria were
      prevalent in all wall paintings monitored (ranging from 18 +/- 2 CFU 100 cm(-2)
      to 68 +/- 4 CFU 100 cm(-2)), whereas fungi were also detected but at lower levels
      (ranging from 9 +/- 2 CFU 100 cm(-2) to 45 +/- 3 CFU 100 cm(-2)). Cultural-based
      method allow us to identify by 16S and 26S rRNA partial sequence analysis
      heterotrophic microorganisms belonging to different genera of Bacillus and
      Aspergillus, Penicillium and Fusarium together with the unusual genera as
      Microascus and Coprinus. By using this approach, Bacillus-related species (B.
      cereus/B. thuringiensis group, B. simplex/B. muralis group, B. megaterium and B.
      subtilis) were isolated in all sample points analysed with the exception of the
      Casa dello Scheletro in which Micrococcus luteus/Arthrobactersp. group and
      Streptomyces fragilis were found. DGGE analysis of PCR amplified V3 region of
      rDNA from DNA directly recovered from frescos samples, enabled identification of
      bacterial species not identified using culturable technology asthose closest
      related to Microbacterium group, often associated with Brevibacterium,
      Streptomyces and Stenotrophomonas. Combination of culture-dependent and
      independent methods provided better microbiology characterization of
      heterotrophic microbiota present on the surface of ancient frescos of this
      important archaeological site.

PMID- 21882664
TI  - Phytoremediation potential of indigenous plants from Thai Nguyen province,
      Vietnam.
AB  - This study was focused on determining Arsenic (As), Lead (Pb), Cadmium (Cd) and
      Zinc (Zn) in 33 indigenous plants and 12 soil in-situ plant samples in Thai
      Nguyen Province, Vietnam. The results showed that the soils of surveyed mining
      areas contained 181.2- 6754.3 mg kg(-1) As, 235.5-4337.2 mg kg(-1) Pb, 0.8- 419
      mg kg(-1) Cd and 361.8-17565.1 mg kg(-1) Zn depending on the characteristics of
      each mining site. These values are much higher than those typical for normal
      soil. The heavy metal uptake into shoots and roots of 33 indigenous plant species
      was also determined. Two species of the plants investigated, Pteris vittata L.
      and Pityrogramma calomelanos L. were As hyperaccumulators, containing more than
      0.1% heavy metals in their shoots. Eleusine indica L., Cynodon dactylon L.,
      Cyperus rotundus L. and Equisetum ramosissimum (Vauch) accumulate very high Pb
      (0.15-0.65%) and Zn (0.22-1.56%) concentration in their roots. Additional
      experiments to clarify the potential of six these plants as good candidates for
      phytoremediation of heavy metal pollution soil are being carried out in our
      laboratory.

PMID- 21882665
TI  - Predicting case conviction and domestic violence recidivism: measuring the
      deterrent effects of conviction and protection order violations.
AB  - Previous research offered little guidance on sentencing outcomes for protection
      order (PO) violations in cases of domestic assault and whether PO violation
      charges affected offender recidivism rates. Using data from local court records,
      this study examined the effect of PO violation charges on the odds of case
      conviction relative to dismissal, and whether case conviction or a PO violation
      charge results in lower domestic violence rearrest rates compared to offenders
      not receiving these sanctions. The models indicate that PO violation charges has
      no significant effect on the odds of conviction or recidivism rates, and these
      trends were not significantly different for convicted versus dismissed offenders.
      Findings are discussed in relation to previous research with recommendations for
      future areas of study.

PMID- 21882666
TI  - College students' electronic victimization in friendships and dating
      relationships: anticipated distress and associations with risky behaviors.
AB  - This study investigated college students' reports of electronic victimization in
      friendships and dating relationships. We examined 22 items representing four
      categories of electronic victimization: hostility, humiliation, exclusion, and
      intrusiveness. Nearly all participants (92%) reported some electronic
      victimization in the past year, with males reporting more victimization and
      females anticipating more distress. Both females and males anticipated more
      distress from electronic victimization in dating relationships than friendships.
      More actual experience with electronic victimization related to lower anticipated
      distress. Electronic victimization was associated with females' alcohol use, even
      after controlling for other victimization experiences. Discussion focuses on the
      contextualized nature of electronic victimization, and on the importance of
      understanding what makes electronic victimization highly distressing for some
      individuals.

PMID- 21882667
TI  - Facilitators and barriers to disclosing abuse among women with disabilities.
AB  - An anonymous audio computer-assisted self-interview (A-CASI) designed to increase
      awareness of abuse was completed by 305 women with diverse disabilities. Data
      were also collected about lifetime and past year abuse; perpetrator risk
      characteristics; facilitators and barriers to disclosing abuse; abuse disclosure
      to a health provider, case manager, or police officer; and whether a health
      provider had ever discussed abuse or personal safety. A total of 276 (90%) women
      reported abuse, 208 (68%) reported abuse within the past year. Women who reported
      the most abuse experiences in the past year and the most dangerous perpetrators
      endorsed fewer facilitators and more barriers, but were also more likely to have
      ever disclosed abuse. Only 15% reported that a health provider had ever discussed
      abuse and personal safety.

PMID- 21882668
TI  - Profiles of distress in sheltered battered women: implications for intervention.
AB  - Heterogeneity in patterns of distress and psychological functioning was
      investigated using a person-oriented approach to data analysis in two diverse
      samples of battered women in shelters. In order to provide some empirically
      derived guidance to clinicians, scores on measures of depressive symptoms as well
      as state and trait anxiety were cluster analyzed. A four-cluster solution
      provided the best fit for both samples of women, and despite the demographic
      differences in the women, generally similar clusters were found in both samples.
      One cluster contained women with minimal distress; another, those who were mildly
      anxious; in a third cluster, the women were moderately to highly depressed and
      anxious; and in a fourth cluster, the women were reporting severe levels of
      distress. Implications for treatment include the importance of providing
      individually tailored interventions for the women, based on differential
      combinations of depression and anxiety, especially for women whose distress
      levels are in the high and severe ranges of distress.

PMID- 21882669
TI  - Posttraumatic symptoms following a campus shooting: the role of psychosocial
      resource loss.
AB  - Conservation of resources (COR) theory has proven a useful framework for
      understanding posttrauma adjustment. A key tenet of this theory is the centrality
      of resource loss in determining adjustment. However, COR theory research has
      often been limited by retrospective research design, a focus on material loss
      (e.g., one's home), and a lack of attention to other adjustment predictors. This
      study examined whether psychosocial resource loss prospectively predicted PTSD
      symptomatology both immediately and 8 months following a campus shooting in a
      sample of college women (n = 691). Results supported that resource loss predicted
      symptomatology, even after controlling for other predictors, including prior
      trauma, psychological distress, initial PTSD symptomatology, and shooting
      exposure. Implications of the results for research and intervention following
      mass trauma are discussed.

PMID- 21882670
TI  - Cumulative victimization, psychological distress, and high-risk behavior among
      substance-involved women.
AB  - This research addressed two questions: (a) What is the relationship between
      different patterns of cumulative victimization and psychological distress? And
      (b) How does the pattern of cumulative victimization and psychological distress
      influence women's engagement in substance- and sex-related risk behavior? Data
      were analyzed from interviews with 149 sexually active, crack-using women who
      completed a follow-up interview after participating in the Kentucky National
      Institute on Drug Abuse (NIDA) AIDS Cooperative Agreement. Findings from the
      multivariate analyses indicated that victimization accounted for 5% and 39% of
      the variance in psychological distress and high-risk behavior, respectively;
      cumulative victimization and psychological distress accounted for 6% to 11% of
      the variance in the high-risk behaviors. Results highlight the affects of
      childhood and adult victimization on psychological distress and the associations
      between different types of psychological distress and risk behavior.

PMID- 21882671
TI  - The relation of violence exposure and ethnicity to intelligence and verbal
      performance discrepancies in incarcerated male adolescents.
AB  - Incarcerated populations have an estimated incidence of intellectual disabilities
      (IDs) far higher than national norms, ranging as high as 10%. In the present
      study, the relation between ID and violence exposure in 115 incarcerated
      adolescents was examined. Interpersonal violence exposure (IPV-E) predicted an
      average decrease in full scale IQ of 4.5 points, explaining approximately 5% of
      the difference in IQ. Child maltreatment increased the odds of having a verbal
      disability by three folds and explained 17% of the variance in verbal disability.
      Hierarchical regression was used to examine the relative contribution of
      ethnicity, poverty, and violence exposure to intellectual functioning. The
      literature on racial bias in incarceration and the implications for the present
      study are discussed.

PMID- 21882672
TI  - The victimization experiences of women in the workforce: moving beyond single
      categories of work or violence.
AB  - The examination of the co-occurrence of different types of victimization in the
      lives of women in the workforce appears infrequently in the literature. We
      examine multiple types of victimization in women's lives across a range of
      employment and income levels. Our research indicates that more than two-thirds of
      women in the workplace experienced at least one type of violence against women
      (VAW). These women hold positions at various workforce levels, indicating that
      victims of VAW are not limited to the lower employment rungs. This research is a
      step toward highlighting the scope, prevalence, and interconnectedness of
      different forms of VAW in the lives of women in the workforce.

PMID- 21882673
TI  - Application of commercial software to the classification of suicide cases: a
      brief report.
AB  - Mosaic Profiler software was used to classify suicide and open verdict cases
      during 1996 to 1998 in England and within England, for the London and the North
      West regions. The classification system was based on the socioeconomic
      characteristics of the last place of residence of the cases at the level of
      postcode. The results highlighted that deprived areas and areas that contain
      elderly population or those areas that suffer from lack of social cohesion are
      overrepresented, whereas affluent areas are underrepresented. All of these,
      although in the larger scale, seem to support the results of other studies.
      Nevertheless, more studies would be required before one can fully evaluate the
      application of the Mosaic Profiler in the field of spatial epidemiology.

PMID- 21882674
TI  - Chemical ecology and management of Lobesia botrana (Lepidoptera: Tortricidae).
AB  - The moth Lobesia botrana (Denis & Schiffermuller) (Lepidoptera: Tortricidae)
      feeds on grapes (Vitis vinifera L.), reducing yield and increasing susceptibility
      to fungal infections. L. botrana is among the most economically important insects
      in Europe and has recently been found in vineyards in Chile, Argentina, and
      California. Here, we review L. botrana biology and behavior in relation to its
      larval host (the grapevine) and its natural enemies. We also discuss current and
      future control strategies in light of our knowledge of chemical ecology, with an
      emphasis on the use of the sex pheromone-based strategies as an environmentally
      safe management approach. Pheromone-mediated mating disruption is the most
      promising technique available on grapes and is currently implemented on
      approximately 140,000 ha in Europe. Experience from several growing areas
      confirms the importance of collaboration between research, extension, growers,
      and pheromone-supply companies for the successful implementation of the mating
      disruption technique. In the vineyards where mating disruption has been
      successfully applied as an areawide strategy, the reduction in insecticide use
      has improved the quality of life for growers, consumers, as well as the public
      living near wine-growing areas and has thereby reduced the conflict between
      agricultural and urban communities.

PMID- 21882675
TI  - A decision-support tool to predict spray deposition of insecticides in commercial
      potato fields and its implications for their performance.
AB  - Approximately US $1.3 billion is spent each year on insecticide applications in
      major row crops. Despite this significant economic importance, there are
      currently no widely established decision-support tools available to assess
      suitability of spray application conditions or of the predicted quality or
      performance of a given commercial insecticide applications. We conducted a field
      study, involving 14 commercial spray applications with either fixed wing airplane
      (N=8) or ground rig (N=6), and we used environmental variables as regression fits
      to obtained spray deposition (coverage in percentage). We showed that (1) ground
      rig applications provided higher spray deposition than aerial applications, (2)
      spray deposition was lowest in the bottom portion of the canopy, (3) increase in
      plant height reduced spray deposition, (4) wind speed increased spray deposition,
      and (5) higher ambient temperatures and dew point increased spray deposition.
      Potato psyllid, Bactericera cockerelli (Sulc) (Hemiptera: Triozidae), mortality
      increased asymptotically to approximately 60% in response to abamectin spray
      depositions exceeding around 20%, whereas mortality of psyllid adults reached an
      asymptotic response approximately 40% when lambda-cyhalothrin/thiamethoxam spray
      deposition exceeded 30%. A spray deposition support tool was developed
      (http://pilcc.tamu.edu/) that may be used to make decisions regarding (1) when is
      the best time of day to conduct spray applications and (2) selecting which
      insecticide to spray based on expected spray deposition. The main conclusion from
      this analysis is that optimization of insecticide spray deposition should be
      considered a fundamental pillar of successful integrated pest management programs
      to increase efficiency of sprays (and therefore reduce production costs) and to
      reduce risk of resistance development in target pest populations.

PMID- 21882676
TI  - Asynchronous development of honey bee host and Varroa destructor (Mesostigmata:
      Varroidae) influences reproductive potential of mites.
AB  - A high proportion of nonreproductive (NR) Varroa destructor Anderson & Trueman
      (Mesostigmata: Varroidae), is commonly observed in honey bee colonies displaying
      the varroa sensitive hygienic trait (VSH). This study was conducted to determine
      the influence of brood removal and subsequent host reinvasion of varroa mites on
      mite reproduction. We collected foundress mites from stages of brood (newly
      sealed larvae, prepupae, white-eyed pupae, and pink-eyed pupae) and phoretic
      mites from adult bees. We then inoculated these mites into cells containing newly
      sealed larvae. Successful reproduction (foundress laid both a mature male and
      female) was low (13%) but most common in mites coming from sealed larvae.
      Unsuccessful reproductive attempts (foundress failed to produce both a mature
      male and female) were most common in mites from sealed larvae (22%) and prepupae
      (61%). Lack of any progeny was most common for mites from white-eyed (83%) and
      pink-eyed pupae (92%). We also collected foundress mites from sealed larvae and
      transferred them to cells containing newly sealed larvae, prepupae, white-eyed
      pupae, or pink-eyed pupae. Successful reproduction only occurred in the transfers
      to sealed larvae (26%). Unsuccessful reproductive attempts were most common in
      transfers to newly sealed larvae (40%) and to prepupae (25%). Unsuccessful
      attempts involved the production of immature progeny (60%), the production of
      only mature daughters (26%) or the production of only a mature male (14%).
      Generally, lack of progeny was not associated with mites having a lack of stored
      sperm. Our results suggest that mites exposed to the removal of prepupae or older
      brood due to hygiene are unlikely to produce viable mites if they invade new
      hosts soon after brood removal. Asynchrony between the reproductive status of
      reinvading mites and the developmental stage of their reinvasion hosts may be a
      primary cause of NR mites in hygienic colonies. Even if reinvading mites use
      hosts having the proper age for infestation, only a minority of them will
      reproduce.

PMID- 21882677
TI  - Performance of Apis mellifera, Bombus impatiens, and Peponapis pruinosa
      (Hymenoptera: Apidae) as pollinators of pumpkin.
AB  - Pollination services of pumpkin, Cucurbita pepo L., provided by the European
      honey bee, Apis mellifera L., were compared with two native bee species, the
      common eastern bumble bee, Bombus impatiens (Cresson), and Peponapis pruinosa
      Say, in New York from 2008 to 2010. Performance of each species was determined by
      comparing single-visit pollen deposition, percentage of visits that contacted the
      stigma, flower-handling time, fruit and seed set, and fruit weight per number of
      visits. Fruit yield from small fields (0.6 ha) supplemented with commercial B.
      impatiens colonies was compared with yield from those not supplemented. A.
      mellifera spent nearly 2 and 3 times longer foraging on each pistillate flower
      compared with B. impatiens and P. pruinosa, respectively. A. mellifera also
      visited pistillate flowers 10-20 times more frequently than B. impatiens and P.
      pruinosa, respectively. Yet, B. impatiens deposited 3 times more pollen grains
      per stigma and contacted stigmas significantly more often than either A.
      mellifera or P. pruinosa. Fruit set and weight from flowers visited four to eight
      times by B. impatiens were similar to those from open-pollinated flowers, whereas
      flowers pollinated by A. mellifera and P. pruinosa produced fewer fruit and
      smaller fruit compared with those from open-pollinated flowers. Fields
      supplemented with B. impatiens produced significantly more pumpkins per plant
      than nonsupplemented fields. B. impatiens was a better pollinator of pumpkin than
      P. pruinosa and should be considered as a promising alternative to A. mellifera
      for pollinating this crop.

PMID- 21882678
TI  - A fluctuating thermal regime improves survival of cold-mediated delayed emergence
      in developing Megachile rotundata (Hymenoptera: Megachilidae).
AB  - A significant concern in the commercial application of the alfalfa leafcutting
      bee, Megachile rotundata (F.) (Hymenoptera: Megachilidae), for pollination is
      synchronizing bee emergence and activity with peak crop bloom. Previous studies
      have demonstrated that the commercial spring incubation of this species can be
      successfully interrupted by low temperature incubation, thereby slowing
      development and giving producers flexibility in timing emergence to weather
      conditions or crop bloom. In this study, we demonstrate that the implementation
      of a fluctuating thermal regime, during which bees are given a daily one hour
      pulse of high temperature, markedly increases the "shelf-life" of individuals of
      this species. Although constant temperatures can be used to store bees for up to
      1 wk with no decrease in survival, properly staged bees can be stored for up to 6
      wk without a significant decrease in percentage of emergence. Hence, we expect
      fluctuating thermal regime protocols to become a valuable tool for M. rotundata
      managers, especially when timing nesting activity with peak bloom to maximize
      effectiveness.

PMID- 21882679
TI  - Species composition of aphid vectors (Hemiptera: Aphididae) of barley yellow
      dwarf virus and cereal yellow dwarf virus in Alabama and western Florida.
AB  - Yellow dwarf is a major disease problem of wheat, Triticum aestivum L., in
      Alabama and is estimated to cause yield loss of 21-42 bu/acre. The disease is
      caused by a complex of viruses comprising several virus species, including Barley
      yellow dwarf virus-PAV and Cereal yellow dwarf virus-RPV. Several other strains
      have not yet been classified into a specific species. The viruses are transmitted
      exclusively by aphids (Hemiptera:Aphididae). Between the 2005 and 2008 winter
      wheat seasons, aphids were surveyed in the beginning of each planting season in
      several wheat plots in Alabama and western Florida Collected aphids were
      identified and bioassayed for their yellow dwarf virus infectivity. This survey
      program was designed to identify the aphid species that serve as fall vectors of
      yellow dwarf virus into winter wheat plantings. From 2005 to 2008, bird cherry
      oat aphid, Rhopalosiphum padi (L.); rice root aphid, Rhopalosiphum rufiabdominale
      (Sasaki); and greenbug, Schizaphis graminum (Rondani), were found consistently
      between October and December. The species of aphids and their timing of
      appearance in wheat plots were consistent with flight data collected in North
      Alabama between 1996 and 1999. Both R. padi and R. rufiabdominale were found to
      carry and transmit Barley yellow dwarf virus-PAV and Cereal yellow dwarf virus
      RPV. The number of collected aphids and proportion of viruliferous aphids were
      low. Although this study has shown that both aphids are involved with
      introduction of yellow dwarf virus to winter wheat in Alabama and western
      Florida, no conclusions can be made as to which species may be the most important
      vector of yellow dwarf virus in the region.

PMID- 21882680
TI  - Cold treatment of Ceratitis capitata (Diptera: Tephritidae) in oranges using a
      larval endpoint.
AB  - South Africa currently exports fresh citrus (Citrus spp.) fruit to Japan using an
      in-transit cold treatment protocol of 14 d or 12 d at temperatures <0 degrees C
      for treatment of Ceratitis capitata (Wiedemann) (Diptera: Tephritidae) in
      'Clementine' mandarins (Citrus reticulata Blanco) and other citrus types,
      respectively. To reduce the risk of chilling injury with this treatment, research
      was conducted with temperatures >0 degrees C. Earlier South African research had
      shown that young (6-d-old) larvae were slightly more tolerant of cold treatment
      and that there were no significant differences between cold tolerance of these
      larvae in different citrus types [oranges, Citrus sinensis (L.) Osbeck;
      grapefruits, Citrus paradisi Macfad.; lemons, Citrus limon (L.) Burm.f.; and
      mandarins). Due to their ready availability, 'Valencia' oranges were used in this
      study. When 62,492 larvae in total were treated in three replicates at a mean
      temperature of 1.5 degrees C for 16 d, there were three larval survivors. The
      trial was therefore repeated with oranges using a 16-d period at a mean
      temperature of 1.0 degrees C and a mean of 1.4 degrees C for the hourly maximum
      probe readings. Three replicates were again conducted and the resultant mean
      mortality in the control was 8.1% of 21,801 larvae, whereas the cold treatment
      mortality was 100% of 71,756 larvae. This treatment at a mean temperature of 1
      degree C exceeded the Japanese confidence level requirement and also exceeded the
      Probit-9 mortality level, but not at a confidence level of 95%. These data
      support the establishment of a treatment protocol of 16 d at temperatures <1.4
      degrees C, commencing once all fruit pulp probes reach a temperature of 1 degree
      C or lower.

PMID- 21882681
TI  - Cold susceptibility and disinfestation of Bactrocera invadens (Diptera:
      Tephritidae) in oranges.
AB  - To develop a cold disinfestation treatment for the fruit fly Bactrocera invadens
      Drew, Tsuruta & White (Diptera: Tephritidae) that is rapidly spreading across
      Africa, research was conducted in Nairobi, Kenya, using flies from a laboratory
      culture and 'Valencia' orange (Citrus sinensis L. Osbeck) as the host. The
      developmental rate of B. invadens in Valencia oranges was determined at 28
      degrees C, and the third instar was found to be the least susceptible of the egg
      and larval life stages to cold treatment at 1.1 degrees C in oranges. When 22,449
      B. invadens third instars were exposed in oranges to a cold treatment with an
      approximate midpoint of 1.1 +/- 0.5 degrees C, the results suggested that a
      period of 16 d would be worthwhile verifying on a larger scale in oranges.
      Results from the first replicate of 16,617 larvae showed no survivors, but the
      second replicate of 23,536 larvae had three survivors. Because a longer cold
      treatment based on a mean temperature of 1.1 degrees C would create logistical
      difficulties for some export markets, further replicates were conducted at an
      approximate midpoint of 0.5 degrees C and at mean hourly maximum of 0.9 +/- 0.5
      degrees C, for 16 d. After three replicates, in which 65,752 B. invadens third
      instars in total were treated with no survivors, the Japanese requirement of
      99.99% mortality at the 95% confidence level was surpassed. The following
      treatment protocol for B. invadens larvae in oranges can therefore be
      recommended: fruit pulp to be maintained at temperatures of 0.9 degrees C or
      lower for 16 consecutive days.

PMID- 21882682
TI  - Evidence of female-produced sex pheromone of Adelphocoris suturalis (Hemiptera:
      Miridae): effect of age and time of day.
AB  - After the reduction in the use of broad-spectrum insecticides, Adelphocoris
      suturalis (Hemiptera: Miridae) has become an important pest of transgenic cotton,
      Gossypium hirsutum L., in China. A. suturalis is a highly mobile insect, moving
      rapidly in and out of crop fields, and traps baited with sex pheromones may be
      useful in monitoring and controlling its numbers. However, little is currently
      known regarding the chemical communication based on sex pheromones by this
      species. To use the synthesized sex pheromone effectively as part of the
      integrated pest management, some fundamental biological parameters under which
      the pheromone is produced must be understood. In this study, attractiveness of
      adult females or males of A. suturalis to conspecific individuals was examined by
      Y-tube bioassay; we also investigated the female sexually mature age and
      circadian rhythm of male attraction to females of A. suturalis in the field in
      2008 and 2010. Y-tube bioassay results indicated that only males were attracted
      to odors from sexually mature virgin females. Two-year field trapping experiments
      showed that 4-18-d-old virgin females effectively attracted males, and males were
      attracted to virgin females during the scotophase, with a peak between 1900 and
      2300 hours. These results improve our understanding of the sexual communication
      behavior of A. suturalis and provide evidence of female-produced sex pheromone in
      this species.

PMID- 21882683
TI  - A novel attractant for Anastrepha ludens (Diptera: Tephritidae) from a Concord
      grape product.
AB  - An attractant for Mexican fruit fly, Anastrepha ludens (Loew) (Diptera:
      Tephritidae), was developed from a commercial product called Sabor Uva containing
      processed Concord grape juice. The principal volatile components of Sabor Uva
      aroma were identified and an aqueous mixture of 15 components that was gas
      chromatographically similar to Sabor Uva was prepared. This mixture was
      equivalent to Sabor Uva in attractiveness by using wind-tunnel bioassays. After
      deleting chemicals that did not contribute to attractiveness, and increasing the
      concentrations of the remaining chemicals, the final attractant contained
      propylene glycol (90,000 ppm, vol/vol), acetic acid (4500), methyl anthranilate
      (1800), ethyl 2-methylpropionate (670), and one or both of the esters ethyl 3
      methylbutyrate (44) and 2-methylbutyl propionate (44), in aqueous solution. This
      mixture was approximately 1.8X as attractive as Sabor Uva by indirect comparison.
      Deletion of propylene glycol, acetic acid, methyl anthranilate, or ethyl 2
      methylpropionate from the mixture significantly decreased attractiveness.
      Deletion of either of the other two esters seemed to diminish attractiveness
      although effects were not statistically significant. Deletion of water from the
      mixture significantly decreased attractiveness. We conclude that propylene
      glycol, acetic acid, methyl anthranilate, water, and at least one or as many as
      all three of the methyl-branched esters are essential for complete
      attractiveness.

PMID- 21882684
TI  - Anastrepha ludens and Anastrepha serpentina (Diptera: Tephritidae) do not infest
      Psidium guajava (Myrtaceae), but Anastrepha obliqua occasionally shares this
      resource with Anastrepha striata in nature.
AB  - This study examined whether economically important fruit fly species Anastrepha
      ludens (Loew), Anastrepha serpentina (Wiedemann), and Anastrepha obliqua
      (Macquart) (Diptera: Tephritidae) may opportunistically exploit guavas, Psidium
      guajava L. (Myrtaceae), growing near preferred natural hosts. We collected 3,459
      kg of guavas and 895 kg of other known host species [sour orange, Citrus
      aurantium L.; grapefruit, Citrus paradisi Macfadyen; mango, Mangifera indica L.;
      white sapote, Casimiroa edulis La Llave and Lex.; sapote, Pouteria sapota
      (Jacq.); sapodilla, Manilkara zapota L.; and wild plum, Spondias purpurea L. and
      Spondias mombin L.] along an altitudinal gradient over a 4-yr period (2006-2009).
      Plants were growing in sympatry in 23 localities where the guavas are usually
      infested in the state of Veracruz, M6xico. The guava samples yielded 20,341
      Anastrepha spp. pupae in total (overall mean, 5.88 pupae per kg of fruit).
      Confirming previous reports, Anastrepha fraterculus (Wiedemann) and Anastrepha
      striata (Schiner) were found heavily infesting guavas in Veracruz. Importantly,
      although we did not find evidence that A. ludens and A. serpentina are able to
      attack this valuable commodity, we document for the first time in the
      agriculturally important state of Veracruz that P. guajava is an alternative
      natural host plant of A. obliqua. We recovered two fruit in the mango-growing
      locality of la Vibora, Tlalixcoyan, that harbored larvae of A. striata and A.
      obliqua. This finding has important practical implications for management of A.
      obliqua. Over the entire altitudinal gradient, when individual fruit infestation
      was examined, a dynamic pattern of species dominance was unveiled with guavas
      growing below 800 m above sea level mainly attacked by A. striata and a
      progressive replacement with increasing altitude by A. fraterculus.
      Interestingly, most individual fruit examined (97%) harbored a single species of
      fruit fly, a finding that may be taken as evidence of competitive displacement
      among sympatric species of fruit flies. Based on this study and previously
      published work by us on this topic, we conclude that literature reports
      indicating that A. ludens and A. serpentina infest guavas under field conditions
      should be questioned.

PMID- 21882685
TI  - Chemical composition and fumigant toxicity of some essential oils against
      Ephestia kuehniella.
AB  - The chemical constituents of some essential oils extracted from aromatic plants
      (savory, Satureja thymbra L.; Turkish oregano, Origanum onites L.; myrtle, Myrtus
      communis L.; marjoram, Origanum majorana L.; laurel, Laurus nobilis L.; lemon,
      Citrus limon L.; sticky goosefoot, Chenopodium botrys L.; and tansy, Tanecetum
      armenum [DC.] Suchultz Bip.) were analyzed by gas chromatography-mass
      spectrometry. Fumigant toxicity of volatile compounds was tested against
      Mediterranean flour moth, Ephestia kuehniella (Zeller) (Lepidoptera: Pyralidae),
      eggs and adults. Percentage of mortality and longevity of E. kuehniella adults
      were estimated after essential oil treatments. LC50 and LC99 values were
      determined for each exposure time for each essential oil. Marjoram and lemon oils
      were the most effective of all the essential oils tested. The major components
      were linalool, 1.8-cineole, citral, 2-(4a.8-dimethyl-1.2.3.4.4a.5.6.7-octahydro
      naphthalen-2-yl)-prop-2-en-l-ol, and p-cymene for marjoram, laurel, lemon,
      goosefoot, and tansy, respectively. The LC50 and LC99 values were estimated as
      3.27 and 5.13 microl liter(-1) air for marjoram and 4.05 and 5.57 microl liter(
      1) air for lemon essential oils at the longest exposure time. Decreasing
      longevity effect of marjoram and lemon was more prominent compared with other
      essential oils. We suggest that essential oils obtained from certain aromatic
      plants have potential as fumigants for stored product pests.

PMID- 21882686
TI  - Chemical composition and acaricidal properties of Deverra scoparia essential oil
      (Araliales: Apiaceae) and blends of its major constituents against Tetranychus
      urticae (Acari: Tetranychidae).
AB  - The essential oil of Deverra scoparia Coss. & Durieu was investigated for its
      acaricidal activity against the worldwide pest twospotted spider mite,
      Tetranychus urticae Koch (Acari: Tetranychidae). The essential oil was analyzed
      by fast gas chromatography (GC) and GC-mass spectrometry. The activities of its
      individual and blended constituents were determined. Our study showed that female
      mortality increased with increasing D. scoparia oil concentrations, with LD50 and
      LD90 values at 1.79 and 3.2 mg liter(-1), respectively. A reduction in fecundity
      had already been observed for concentrations of 0.064, 0.08, and 0.26 mg liter(
      1) D. scoparia essential oil. Ten major components, comprising 98.52% of the
      total weight, were identified; a-pinene was the most abundant constituent
      (31.95%) followed by sabinene (17.24%) and delta3-carene (16.85%). The 10 major
      constituents of D. scoparia oil were individually tested against T. urticae
      females. The most potent toxicity was found with alpha-pinene, delta3-carene, and
      terpinen-4-ol. The presence of all constituents together in the artificial
      mixture caused a significant decrease in the number of eggs laid by females, at
      0.26 mg liter(-1) (11 eggs), compared with the control (50 eggs). The toxicity of
      blends of selected constituents indicated that the presence of all constituents
      was necessary to reproduce the toxicity level of the natural oil.

PMID- 21882687
TI  - Long-term effects of methoxyfenozide on the adult reproductive processes and
      longevity of Spodoptera exigua (Lepidoptera: Noctuidae).
AB  - The long-term effects of methoxyfenozide on the longevity and reproductive
      processes of beet armyworm, Spodoptera exigua (Hubner) (Lepidoptera: Noctuidae),
      adults were assessed after exposure by ingestion. Methoxyfenozide significantly
      reduced adult male longevity compared with females by 1.1 and 1.5 d at 75 and 150
      mg (AI)/liter, respectively. Fecundity decreased by >60% with both concentrations
      at 72 and 96 h after treatment, but at 48 h, no significant effect was observed.
      The carbohydrate, protein, and lipid content in the eggs were determined as
      representatives of the biochemical effects of methoxyfenozide associated with the
      disruption of reproductive processes. The content of carbohydrates in the eggs
      laid 48 h at treatment was similar to that of controls, but it increased by
      approximately 1.5 and 2-fold in eggs laid after 72 and 96 h, respectively,
      compared with controls (15 microg per egg). Protein content was reduced
      approximately 2.5 and approximately 3-fold for each treatment concentration,
      respectively, compared with the controls (25 and 23 microg per egg for 75 and 150
      mg [AI]/liter, respectively) in eggs collected 72 and 96 h after treatment. Lipid
      content significantly decreased by approximately 1.6-fold in both treatment
      concentrations in eggs collected at 48 and 96 h after treatment compared with the
      controls (24 and 21 microg per egg for 48 and 96, respectively), but it was
      similar to controls (approximately 19 microg per egg) at 72 h (approximately 15
      microg per egg) for both concentrations. The biochemical effects of
      methoxyfenozide on S. exigua egg formation detected in this work are consistent
      with the reduction in fertility observed, as reported previously.

PMID- 21882688
TI  - Impact of planting dates on a seed maggot, Neotephritis finalis (Diptera:
      Tephritidae), and sunflower bud moth (Lepidoptera: Tortricidae) damage in
      cultivated sunflower.
AB  - Neotephritisfinalis (Loew) (Diptera: Tephritidae), and sunflower bud moth,
      Suleima helianthana (Riley) (Lepidoptera: Tortricidae) are major head-infesting
      insect pests of cultivated sunflower (Helianthus annuus L.). Planting date was
      evaluated as a cultural pest management strategy for control of N. finalis and S.
      helianthana in several production regions of North Dakota during 2009 and 2010.
      Results of the nine site-year study revealed that late planting date (early to
      mid-June) reduced damage ratings and percentage of damaged heads for N. finalis
      compared with early planting dates (mid- to late May). Visual observations of
      adult N. finalis found that the majority of flies were found in the early planted
      sunflower (78.2%) compared with the late planted sunflower (21.8%). Late planting
      date also reduced the percentage of S. helianthana damaged heads compared with
      early planting dates. Yield losses were reduced with late planting date when
      populations of N. finalis and S. helianthana were high enough to cause damage.
      Results of this study showed that delayed planting is an effective integrated
      pest management strategy that can reduce head damage caused by N. finalis and S.
      helianthana and mitigate yield losses.

PMID- 21882689
TI  - Bark beetle pheromones and pine volatiles: attractant kairomone lure blend for
      longhorn beetles (Cerambycidae) in pine stands of the southeastern United States.
AB  - In 2006, we examined the flight responses of 43 species of longhorn beetles
      (Coleoptera: Cerambycidae) to multiple-funnel traps baited with binary lure
      blends of (1) ipsenol + ipsdienol, (2) ethanol + alpha-pinene, and a quaternary
      lure blend of (3) ipsenol + ipsdienol + ethanol + alpha-pinene in the
      southeastern United States. In addition, we monitored responses of Buprestidae,
      Elateridae, and Curculionidae commonly associated with pine longhorn beetles.
      Field trials were conducted in mature pine (Pinus pp.) stands in Florida,
      Georgia, Louisiana, and Virginia. The following species preferred traps baited
      with the quaternary blend over those baited with ethanol + alpha-pinene:
      Acanthocinus nodosus (F.), Acanthocinus obsoletus (Olivier), Astylopsis arcuata
      (LeConte), Astylopsis sexguttata (Say), Monochamus scutellatus (Say), Monochamus
      titillator (F.) complex, Rhagium inquisitor (L.) (Cerambycidae), Buprestis
      consularis Gory, Buprestis lineata F. (Buprestidae), Ips avulsus (Eichhoff), Ips
      calligraphus (Germar), Ips grandicollis (Eichhoff), Orthotomicus caelatus
      (Eichhoff), and Gnathotrichus materiarus (Fitch) (Curculionidae). The addition
      ofipsenol and ipsdienol had no effect on catches of 17 other species of bark and
      wood boring beetles in traps baited with ethanol and a-pinene. Ethanol + alpha
      pinene interrupted the attraction of Ips avulsus, I. grandicollis, and
      Pityophthorus Eichhoff spp. (but not I. calligraphus) (Curculionidae) to traps
      baited with ipsenol + ipsdienol. Our results support the use of traps baited with
      a quaternary blend of ipsenol + ipsdienol + ethanol + alpha-pinene for common
      saproxylic beetles in pine forests of the southeastern United States.

PMID- 21882690
TI  - Effect of aerosol surface lubricants on the abundance and richness of selected
      forest insects captured in multiple-funnel and panel traps.
AB  - Survey and detection programs for native and exotic forest insects frequently
      rely on traps baited with odorants, which mediate the orientation of target taxa
      (e.g., the southern pine beetle, Dendroctonusfrontalis Zimmermann) toward a
      resource (e.g., host material, mates). The influence of trap design on the
      capture efficiency of baited traps has received far less empirical attention than
      odorants, despite concerns that intercept traps currently used operationally have
      poor capture efficiencies for some target taxa (e.g., large woodborers). Several
      studies have recently demonstrated that treating traps with a surface lubricant
      to make them "slippery" can increase their capture efficiency; however,
      previously tested products can be expensive and their application time-consuming.
      The purpose of this study was to evaluate the effect of alternate, easier to
      apply aerosol lubricants on trap capture efficiency of selected forest insects.
      Aerosol formulations of Teflon and silicone lubricants increased both panel and
      multiple-funnel trap capture efficiencies. Multiple-funnel traps treated with
      either aerosol lubricant captured significantly more Monochamus spp. and
      Acanthocinus obsoletus (Olivier) than untreated traps. Similarly, treated panel
      traps captured significantly more Xylotrechus sagittatus (Germar), Ips
      calligraphus (Germar), Pissodes nemorensis (Germar), Monochamus spp., A.
      obsoletus, Thanasimus dubius (F.), and Ibalia leucospoides (Hochenwarth) than
      untreated traps. This study demonstrates that treating multiple-funnel and panel
      traps with an aerosol dry film lubricant can increase their capture efficiencies
      for large woodborers (e.g., Cerambycidae) as well as bark beetles, a weevil, a
      woodwasp parasitoid and a bark beetle natural enemy (Coleoptera: Cleridae).

PMID- 21882691
TI  - Field evaluation of effect of temperature on release of disparlure from a
      pheromone-baited trapping system used to monitor gypsy moth (Lepidoptera:
      Lymantriidae).
AB  - Traps baited with disparlure, the synthetic form of the gypsy moth, Lymantria
      dispar (L.) (Lepidoptera: Lymantriidae), sex pheromone are used to detect newly
      founded populations and estimate population density across the United States. The
      lures used in trapping devices are exposed to field conditions with varying
      climates, which can affect the rate of disparlure release. We evaluated the
      release rate of disparlure from delta traps baited with disparlure string
      dispenser from 1 to 3 yr across a broad geographic gradient, from northern
      Minnesota to southern North Carolina. Traps were deployed over approximately 12
      wk that coincided with the period of male moth flight and the deployment schedule
      of traps under gypsy moth management programs. We measured a uniform rate of
      release across all locations when considered over the accumulation of degree
      days; however, due to differences in degree-day accumulation across locations,
      there were significant differences in release rates over time among locations.
      The initial lure load seemed to be sufficient regardless of climate, although
      rapid release of the pheromone in warmer climates could affect trap efficacy in
      late season. Daily rates of release in colder climates, such as Minnesota and
      northern Wisconsin, may not be optimal in detection efforts. This work highlights
      the importance of local temperatures when deploying pheromone-baited traps for
      monitoring a species across a large and climatically diverse landscape.

PMID- 21882692
TI  - Use of systemic fipronil and imidacloprid to control regeneration pests of
      loblolly pine.
AB  - Regeneration pests of loblolly pine (Pinus taeda L.) threaten growth and survival
      in intensively managed loblolly pine plantations throughout the southeastern
      United States. The Nantucket pine tip moth, Rhyacionia frustrana (Comstock), in
      particular, often reduces growth of loblolly pine but has been difficult to
      control with traditional insecticides due to multiple annual generations and
      multi-year infestations which are difficult to predict in timing and location.
      Relatively new systemic insecticide products offer a solution in that their
      efficacy persists through multiple generations and years after a single
      application. Efficacy of systemic imidacloprid and fipronil were evaluated side
      by side across multiple sites in Virginia. Significant reductions in Nantucket
      pine tip moth damage were noted in trees treated with either the imidacloprid or
      fipronil product compared with check trees. After 2 yr, growth improvement of
      treated trees relative to controls was modest and not significant at all sites,
      but per acre volume indices were significantly greater in treated blocks as a
      result of higher tree survival. Reduced seedling mortality was attributed
      primarily to prevention of damage by pales weevil, Hylobius pales Herbst
      (Coleoptera: Curculionidae), by both insecticide treatments. Control of pales
      weevil in addition to pine tip moth suggests that systemic insecticide products
      with a long window of efficacy might control additional nontargeted pests.

PMID- 21882693
TI  - Application of molecular techniques to identification of three plusiine species,
      Autographa nigrisigna, Macdunnoughia confusa, and Thysanoplusia intermixta
      (Lepidoptera: Noctuidae), found in integrated pest management lettuce fields in
      Japan.
AB  - Three plusiine species, Autographa nigrisigna, Macdunnoughia confusa, and
      Thysanoplusia intermixta (Lepidoptera: Noctuidae), are commonly found together in
      lettuce, Lactuca sativa L., fields in Japan. Given the marked morphological
      similarities between these species and the difficulty associated with
      discriminating between them using only visual cues, we used multiplex polymerase
      chain reaction (PCR) assay to distinguish between the three target species.
      Multiplex PCR uses four primers to simultaneously amplify a specific region of
      the mitochondrial DNA and produce species-specific banding patterns. The
      stringency of the method was tested using specimens of different sex, location,
      and developmental stage, and consistent results were obtained for all samples.
      Indeed, our method has the potential to clarify the species structure of plusiine
      species in lettuce fields.

PMID- 21882694
TI  - Temperature thresholds and degree-day model for Marmara gulosa (Lepidoptera:
      Gracillariidae).
AB  - The developmental thresholds for Marmara gulosa Guillen & Davis (Lepidoptera:
      Gracillariidae) were investigated in the laboratory by using 17, 21, 25, 29, and
      33 degrees C. The lowest mortality occurred in cohorts exposed to 25 and 29
      degrees C. Other temperatures caused >10% mortality primarily in egg and first
      and second instar sap-feeding larvae. Linear regression analysis approximated the
      lower developmental threshold at 12.2 degrees C. High mortality and slow
      developmental rate at 33 degrees C indicate the upper developmental threshold is
      near this temperature. The degree-day (DD) model indicated that a generation
      requires an accumulation of 322 DD for development from egg to adult emergence.
      Average daily temperatures in the San Joaquin Valley could produce up to seven
      generations of M. gulosa per year. Field studies documented two, five, and three
      overlapping generations of M. gulosa in walnuts (Juglans regia L.; Juglandaceae),
      pummelos (Citrus maxima (Burm.) Merr.; Rutaceae), and oranges (Citrus sinensis
      (L.) Osbeck; Rutaceae), for a total of seven observed peelminer generations.
      Degree-day units between generations averaged 375 DD for larvae infesting walnut
      twigs; however, availability of green wood probably affected timing of
      infestations. Degree-day units between larval generations averaged 322 for
      pummelos and 309 for oranges, confirming the laboratory estimation. First
      infestation of citrus occurred in June in pummelo fruit and August in orange
      fruit when fruit neared 60 mm in diameter. Fruit size and degree-day units could
      be used as management tools to more precisely time insecticide treatments to
      target the egg stage and prevent rind damage to citrus. Degree-day units also
      could be used to more precisely time natural enemy releases to target larval
      instars that are preferred for oviposition.

PMID- 21882695
TI  - Evaluation of cucurbitacin-based gustatory stimulant to facilitate cucumber
      beetle (Coleoptera: Chrysomelidae) management with foliar insecticides in melons.
AB  - The bitter plant-derived compounds cucurbitacins are known to stimulate feeding
      of adult cucumber beetles (Coleoptera: Chrysomelidae). A cucurbitacin-based
      gustatory stimulant applied as a flowable bait combined with either spinosad or
      carbaryl was compared with foliar sprays of spinosad and carbaryl for controlling
      two cucumber beetle species (Diabrotica undecimpunctata undecimpunctata
      Mannerheim and Acalymma trivittatum Mannerheim) in honeydew melons (Cucumis melo
      L.). Field studies were conducted on the University of California-Davis plant
      pathology farm in 2008 and 2009. Beetle densities after applications and fruit
      damage from beetle feeding were compared among treatments. In addition, beetle
      survival was compared within field cages placed over the treated foliage infested
      with beetles. Using all three measures of efficacy, we determined that the
      addition of cucurbitacin bait had no effect on the level of cucumber beetle
      control with carbaryl in either 2008 or 2009. In both years, spinosad did not
      significantly reduce cucumber beetle densities in either field cages or field
      plots and did not reduce fruit damage relative to the untreated control. The
      addition of the bait to spinosad did not improve its efficacy. A laboratory
      bioassay of the spinosad formulation used in the field showed it had significant
      lethal effects on adults of both cucumber beetle species. Results indicated that
      the bait formulation used did not improve cucumber beetle control but may benefit
      from the addition of floral attractants or using a different type of
      cucurbitacin.

PMID- 21882696
TI  - Comparative fitness of irradiated light brown apple moths (Lepidoptera:
      Tortricidae) in a wind tunnel, hedgerow, and vineyard.
AB  - Light brown apple moth, Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae),
      is the target of the sterile insect technique, but reduced moth fitness from
      irradiation lowers the effective overflooding ratio of sterile to wild moths. New
      measures of insect quality are being sought to improve field performance of
      irradiated insects, thus improving the cost effectiveness of this technique. Male
      pupae were irradiated at intervals between 0 and 300 Gy, and adult flight success
      was assessed in a wind tunnel equipped with flight track recording software. A
      dose response was evident with reduced successful search behaviors at higher
      irradiation doses. Irradiation at 250 Gy reduced arrival success to 49% of
      untreated controls, during 2-min assays. Mark-release-recapture of males
      irradiated at 250 Gy indicated reduced male moth recapture in hedgerows (75% of
      control values of 7.22% +/- 1.20 [SEM] males recaptured) and in vineyards (78% of
      control values 10.5% +/- 1.66% [SEM] recaptured). Males dispersed similar
      distances in both habitats, and overflooding ratios dropped off rapidly from the
      release point in both landscapes. Transects of traps with central releases proved
      to be an efficient method for measuring the quality of released males. Relative
      field performance of moths was greater than suggested by wind tunnel performance,
      which could be due to time differences between the two assays, two-minute wind
      tunnel tests compared with days in the field treatments. Release strategies
      involving ground releases should consider the effect of limited postrelease
      dispersal. Aerial release could solve this problem and warrants investigation.

PMID- 21882697
TI  - Microencapsulated pear ester enhances insecticide efficacy in walnuts for codling
      moth (Lepidoptera: Tortricidae) and navel orangeworm (Lepidoptera: Pyralidae).
AB  - The efficacy of combining insecticides with a microencapsulated formulation of
      ethyl (2E,4Z) -2,4-decadienoate (pear ester, PE-MEC) was evaluated in walnuts,
      Juglans regia L., for codling moth, Cydia pomonella (L.) (Lepidoptera:
      Tortricidae), and navel orangeworm, Amyelois transitella Walker (Lepidoptera,
      Pyralidae). Two types of studies were conducted to compare the use of
      insecticides with and without PE-MEC. In the first study, PE-MEC in combination
      with reduced rates of insecticides, including chlorpyrifos, phosmet,
      methoxyfenozide, and codling moth granulovirus were evaluated in single tree
      replicates. PE-MEC was tested at one to three rates (0.6, 1.8, and 4.4 g active
      ingredient ha(-1)) with each insecticide. In the second study, seasonal programs
      including sprays of esfenvalerate, chlorpyrifos, and ethyl parathion at full
      rates were evaluated in replicated two ha blocks. Significant reductions in nut
      injury occurred in the single-tree trial with treatments of PE-MEC plus
      insecticide compared with the insecticides used alone against both pest species;
      except with methoxyfenozide for navel orangeworm. Similarly, nut injury in the
      large plots was significantly reduced with the addition of PE-MEC, except for
      navel orangeworm in one of the two studies. These results suggest that adding
      pear ester as a microencapsulated spray can improve the efficacy of a range of
      insecticides for two key pests and foster the development of integrated pest
      management tactics with reduced insecticide use in walnut.

PMID- 21882698
TI  - Host suitability and gas exchange response of grapevines to potato leafhopper
      (Hemiptera: Cicadellidae).
AB  - Although potato leafhopper, Empoasca fabae (Harris) (Hemiptera: Cicadellidae), is
      highly polyphagous, classic host studies do not recognize grapevines (Vitis
      spp.), as suitable hosts. Recently, injury has been reported and reproduction
      documented within grape vineyards, suggesting a host expansion for the
      leafhopper. To document this apparent expansion in host use, we determined
      whether grape plants were suitable hosts for potato leafhopper reproduction,
      measured the consequence of feeding injury on gas exchange rates of grape leaves,
      and compared the susceptibility to feeding injury among cultivars. We found that
      potato leafhopper adults survived equally well on grape (Vitis vinifera L.),
      alfalfa (Medicago sativa L.), and fava bean (Vicia faba L.). The total number of
      offspring was greater on fava bean but did not differ between alfalfa and grape.
      Injury to grapevines was assessed by measuring gas exchange responses of leaves
      in field cages and in greenhouse tests. We found marginally significant declines
      in photosynthesis and transpiration rates in the field (9.6 and 13.2%,
      respectively), and much stronger effects in greenhouse tests (ranging between 22
      and 52%). Our results verify that Vitis is a suitable host, and that potato
      leafhopper is capable of injuring its gas exchange physiology. We discuss
      possible explanations for the host expansion, and its potential to damage
      commercial grapevines.

PMID- 21882699
TI  - Accuracy, precision, and economic efficiency for three methods of thrips
      (Thysanoptera: Thripidae) population density assessment.
AB  - Western flower thrips, Frankliniella occidentalis (Pergande) (Thysanoptera:
      Thripidae), is a major horticultural pest and an important vector of plant
      viruses in many parts of the world. Methods for assessing thrips population
      density for pest management decision support are often inaccurate or imprecise
      due to thrips' positive thigmotaxis, small size, and naturally aggregated
      populations. Two established methods, flower tapping and an alcohol wash, were
      compared with a novel method, plant desiccation coupled with passive trapping,
      using accuracy, precision and economic efficiency as comparative variables.
      Observed accuracy was statistically similar and low (37.8-53.6%) for all three
      methods. Flower tapping was the least expensive method, in terms of person-hours,
      whereas the alcohol wash method was the most expensive. Precision, expressed by
      relative variation, depended on location within the greenhouse, location on
      greenhouse benches, and the sampling week, but it was generally highest for the
      flower tapping and desiccation methods. Economic efficiency, expressed by
      relative net precision, was highest for the flower tapping method and lowest for
      the alcohol wash method. Advantages and disadvantages are discussed for all three
      methods used. If relative density assessment methods such as these can all be
      assumed to accurately estimate a constant proportion of absolute density, then
      high precision becomes the methodological goal in terms of measuring insect
      population density, decision making for pest management, and pesticide efficacy
      assessments.

PMID- 21882700
TI  - Ecology and management of the woolly whitefly (Hemiptera: Aleyrodidae), a new
      invasive citrus pest in Ethiopia.
AB  - Distribution and importance of woolly whitefly (Aleurothrixus floccosus)
      (Maskell) (Hemiptera: Aleyrodidae), was studied in Ethiopia with an evaluation of
      treatments against it. Results showed that the pest is distributed in most citrus
      growing parts of the country equally infesting all types of citrus crops. Only
      one pupal parasitoid, Amitus sp., was recorded at Melkaoba. During 2006-2007,
      eight treatments gave better control of woolly whitefly compared with the
      control: endod (Phytolacca dodecandra L'Herit) berry extract, white oil 80%, neem
      oil, omo detergent soap, band application of gasoline, cyhalothrin (karate) 5%
      EC, selecron (profenofos) 500 EC, and rimon (novaluron) 10 EC. Treatments were
      applied on 6-8 yr-old orange trees at Melkaoba and Nazareth. At Melkaoba,
      application of cyhalothrin, selecron, white oil, and Neem gave better control of
      woolly whitefly compared with the control. All the treatments resulted in a lower
      number of ants than the control. Ants disrupt biocontrol agents of honeydew
      secreting pests, including woolly whiteflies. Mean infestation score was higher
      in the control than the rest of the treatments. Similarly, at Nazareth, woolly
      whitefly numbers were lower recorded on cyhalothrin-treated plants. However, the
      numbers of eggs were significantly higher in endod extract-sprayed plants than
      the control. All treatments controlled ants better than the control except endod.
      Infestation scores were lower on endod- and cyhalothrin-treated plants than the
      control. Mean number of adult woolly whiteflies and eggs were significantly
      higher on newly grown leaves than older leaves. In general, the number of live
      adult woolly whiteflies showed a decreasing trend at both sites after treatment
      applications compared with the control.

PMID- 21882701
TI  - Effectiveness of commercial and experimental termite monitors for the desert
      subterranean termite Heterotermes aureus (Isoptera: Rhinotermitidae) in southern
      Arizona.
AB  - In Arizona, the subterranean termite Heterotermes aureus (Snyder) (Isoptera:
      Rhinotermitidae) is the most economically important termite pest. We report here
      the evaluation of several commercial and experimental monitoring stations to
      capture and monitor H. aureus. In total, 12 monitoring stations were evaluated
      over two study periods. In 2001-2002, the commercial monitors Firstline and
      Termicon did not capture any H. aureus, whereas Termitrol did not capture
      significantly more termites than these two monitors. In contrast, three
      experimental Arizona Research Monitoring Stations (ARMS)--ARMS-PINE, ARMS-ASH,
      and ARMS-BBT--captured significantly more termites than Firstline and Termicon,
      and ARMS-BBT captured termites significantly more frequently than the commercial
      monitors. Similarly in 2003, the commercial monitors Firstline and Defender did
      not capture any H. aureus, whereas Extera did not capture significantly more
      termites than these two monitors. However, four monitor designs including the
      three most successful ARMS in 2001-2002 captured significantly more termites than
      Firstline and Defender, and ARMS-ASH captured termites significantly more often
      than the commercial monitors. On-ground ARMS monitors in general captured
      significantly more termites than commercial in-ground stations.

PMID- 21882702
TI  - Generating susceptible strain and resistance status of field populations of
      Spodoptera exigua (Lepidoptera: Noctuidae) against some conventional and new
      chemistry insecticides in Pakistan.
AB  - Two field populations of Spodoptera exigua (Hubner) (Lepidoptera: Noctuidae) from
      Dera Ghazi Khan (D. G. Khan) and Multan, Pakistan, were tested for resistance to
      the 10 most commonly used insecticides in Pakistan by using a standard leaf disc
      bioassay on the F1 progeny. For comparison, a susceptible strain was generated
      from the Multan strain, which displayed lower LC50 values for most of the
      insecticides, by either mass rearing without exposure to insecticides or single
      pair crosses against selected insecticides. The single-pair crosses generated a
      more susceptible strain than mass rearing. The D. G. Khan field strain was highly
      resistant to cypermethrin, profenofos, spinosad, abamectin, and chlorpyrifos and
      moderately resistant to deltamethrin, indoxacarb, and methoxyfenozide compared
      with susceptible lab strain. The Multan strain was highly resistant to profenofos
      and indoxacarb. Both field populations were susceptible to emamectin benzoate and
      lufenuron. Rotating these two insecticides with others that show very low, low,
      or moderate levels of resistance and have different modes of action may be useful
      for the effective management of this pest.

PMID- 21882703
TI  - Cross-resistance to insecticides in a malathion-resistant strain of Ceratitis
      capitata (Diptera: Tephritidae).
AB  - Resistance to malathion has been reported in field populations of the
      Mediterranean fruit fly, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae),
      in areas of Spain where an intensive use of this insecticide was maintained for
      several years. The main goal of this study was to determine whether resistance to
      malathion confers cross-resistance to different types of insecticides.
      Susceptibility bioassays showed that the malathion-resistant W-4Km strain (176
      fold more resistant to malathion than the susceptible C strain) has moderate
      levels of cross-resistance (three- to 16-fold) to other organophosphates
      (trichlorphon, diazinon, phosmet and methyl-chlorpyrifos), the carbamate
      carbaryl, the pyrethroid lambda-cyhalothrin, and the benzoylphenylurea derivative
      lufenuron, whereas cross-resistance to spinosad was below two-fold. The W-4Km
      strain was selected with lambda-cyhalothrin to establish the lambda-cyhalothrin
      resistant W-1Klamda strain (35-fold resistant to lambda-cyhalothrin). The
      synergistic activity of the esterase inhibitor DEF with lambda-cyhalothrin and
      the increase in esterase activity in the W-1Klamda strain suggests that esterases
      may be involved in the development of resistance to this insecticide. Our results
      showed that resistance to malathion may confer some degree of cross-resistance to
      insecticides currently approved for the control of Mediterranean fruit fly in
      citrus crops (lambda-cyhalothrin, lufenuron, and methyl-chlorpyrifos). Especially
      relevant is the case of lambda-cyhalothrin, because we have shown that resistance
      to this insecticide can rapidly evolve to levels that may compromise its
      effectiveness in the field.

PMID- 21882704
TI  - An aphid-dip bioassay to evaluate susceptibility of soybean aphid (Hemiptera:
      Aphididae) to pyrethroid, organophosphate, and neonicotinoid insecticides.
AB  - Since the discovery of the soybean aphid, Aphis glycines Matsumura (Hemiptera:
      Aphididae), in North America in 2000, chemical control has been the most
      effective method to manage aphid outbreaks. Increased insecticide use in soybean
      raises the possibility of developing insecticide resistance in soybean aphid, and
      monitoring insecticide susceptibility is essential to maintain pesticide tools.
      We developed a simple and reliable aphid-dip bioassay by using a tea strainer
      that resulted in -90% survival in controls. Using this technique, we tested
      susceptibility of a greenhouse strain of soybean aphid that has never been
      exposed to insecticides, and field-collected aphid strains from two counties in
      Michigan. Aphid susceptibility was tested for five insecticides by dipping groups
      of five aphids in each insecticide dose for 10 s. After 48 h, aphids were
      classified as dead or alive, and counted. Aphids from all strains were highly
      susceptible to chlorpyrifos, lambda-cyhalothrin, esfenvalerate, and dimethoate,
      with LC50 and LC90 values well below the recommended application rates. However,
      aphids showed less susceptibility after 48 h to neonicotinoid imidacloprid, with
      higher LC90s and wider fiducial limits. This illustrated the potential limitation
      of using a 48-h assay to evaluate insecticides with longer-term, sublethal
      impacts. Nevertheless, this study made use of a simple aphid-dip method to test
      and compare insecticide susceptibility of soybean aphid. In the event of a field
      failure, the aphid populations involved can be tested in comparison to a
      susceptible greenhouse strain to determine the extent of resistance development.

PMID- 21882705
TI  - Differential resistance and cross-resistance to three phenylpyrazole insecticides
      in the planthopper Nilaparvata lugens (Hemiptera: Delphacidae).
AB  - Cross-resistance to two fipronil analogs, butene-fipronil and ethiprole, was
      detected in fipronil-resistant field populations and a resistant laboratory
      strain of the planthopper Nilaparvata lugens (Stal) (Hemiptera: Delphacidae),
      although the two analogs have not been used widely in rice-growing areas in
      China. The results showed that six field populations with 23.8-43.3-fold
      resistance to fipronil had reached a higher level of cross-resistance to
      ethiprole (resistance ratio [RR] = 47.1-100.9-fold) and had a minor level of
      cross-resistance (RR = 3.4- 8.1-fold) to butene-fipronil. After 10 generations of
      selection, the RR to fipronil increased from 7.3-fold to 41.3-fold. At the same
      time, the insect increased cross-RR to ethiprole from 16.3-fold to 65.6-fold,
      whereas it had only minor increase in cross-resistance to butene-fipronil from
      2.8-fold to 4.0-fold. These results confirmed that fipronil-resistant N. lugens
      could develop a higher level of cross-resistance to ethiprole, although it still
      maintained a lower level cross-resistance to butene-fipronil. Our data suggest
      that ethiprole is not a suitable alternative for controlling N. lugens, once the
      insect has developed a high level resistance to fipronil. Further investigation
      is necessary to understand the cross-resistance mechanisms in N. lugens.

PMID- 21882706
TI  - Behavioral responses and bioefficacy of some aromatic amides against Aedes
      aegypti.
AB  - A series of substituted aromatic amides by varying the chain length, substitution
      of methyl, methoxy, chloro, and fluoro groups at ortho-, meta-, and para
      positions of the phenyl ring of N,N-diethyl-2-phenylacetamide were synthesized.
      Laboratory studies were carried out to observe the behavioral responses and
      repellent activity of these newly synthesized aromatic amides against Aedes
      aegypti (L.) mosquitoes. The deterrent activity of these synthetic amides against
      any vectors has not been reported previously. These aromatic amides were tested
      for their behavioral responses and compared with the well known insect
      repellents, namely, N,N-diethyl toluamide; N,N-diethyl phenylacetamide; and N,N
      diethylbenzamide. Out of the 14 compounds synthesized, seven compounds were
      selected on the basis of those showing >75% of repellent response for the
      bioefficacy test on human volunteers. The potential use of lead compounds in
      personal protection management is discussed.

PMID- 21882707
TI  - Effect of vermicompost and cucumber cultivar on population growth attributes of
      the melon aphid (Hemiptera: Aphididae).
AB  - Worldwide, the developing industry of cucumbers (Cucumis sativus L.) grown in
      greenhouses is threatened by damage from sucking pests, especially aphids. Among
      these, the melon aphid, Aphis gossypii Glover (Hemiptera: Aphididae), is the most
      serious. We tested the effect of two cucumber cultivars ('Royal' and'Storm') and
      three vermicompost concentrations (0 [control], 20, and 30%) in field soil on the
      development and fecundity rates of A. gossypii, by using a randomized complete
      block design with four replicates as a factorial experiment. The developmental
      times of nymphs reared on plants grown into the three vermicompost concentrations
      ranged from 5.5 (0%) to 8.7 (30%) d (on Storm) and from 4.3 (0%) to 7 (30%) d (on
      Royal). The developmental time of melon aphid's nymphs was greatest on plants
      grown in the culture medium with 30% vermicompost rate and least on plants reared
      in the soil without vermicompost. The intrinsic rate of natural increase (r,,) of
      A. gossypii ranged from 0.204 d(-1) on plants grown in the soil amended with 30%
      vermicompost rate (on Storm seedlings) to 0.458 d(-1) on plants grown in the soil
      without vermicompost (on Royal seedlings). Accordingly, our findings confirm that
      a combination of a low level of vermicompost and a partially resistant cucumber
      cultivar might play an important role in managing this aphid on cucumbers in
      greenhouses.

PMID- 21882708
TI  - Changes in phytohormones and fatty acids in wheat and rice seedlings in response
      to Hessian fly (Diptera: Cecidomyiidae) infestation.
AB  - Phytohormones and fatty acids (FAs) play important roles in plant resistance to
      insects and pathogens. In this study, we investigated the similarities and
      differences in the accumulations of phytohormones and FAs in the resistant wheat
      (Triticum aestivum L.) 'Molly' and the nonhost rice (Oryza sativa L.) 'Niponbare'
      in responses to Hessian fly, Mayetiola destructor (Say) (Diptera: Cecidomyiidae),
      larval attacks. Using chemical ionization-gas-chromatography/mass spectrometry,
      we analyzed the concentrations of 13 phytohomones and FAs at the attack site of
      wheat and rice plants at 1, 6, 24, or 48 h after the initial attack. Hessian fly
      attack resulted in increases of salicylic acid (SA), 12-oxo-phytodienoic acid
      (OPDA), palmitic acid (FA16:0), but a decrease of abscisic acid in both wheat and
      rice plants. In addition, the accumulation of jasmonic acid (JA) increased,
      whereas the accumulation of cinnamic acid (CA) decreased in wheat plants, but no
      changes were observed in the accumulation of JA, and the accumulation of CA
      increased in rice plants after Hessian fly attack. However, the accumulations of
      benzoic acid, strearic acid (FA18:0), and oleic acid (FA18:1) increased in rice
      plants, but no changes were observed in wheat plants after Hessian fly attack.
      Hessian fly-induced changes were more rapid in wheat plants in comparison with
      those in rice plants. Our study suggests that SA and OPDA may be involved in
      resistance of wheat and rice plants to Hessian fly and that the R gene-mediated
      resistance responses are more rapid than nonhost resistance responses.

PMID- 21882709
TI  - No fitness cost for wheat's H gene-mediated resistance to Hessian fly (Diptera:
      Cecidomyiidae).
AB  - Resistance (R) genes have a proven record for protecting plants against biotic
      stress. A problem is parasite adaptation via Avirulence (Avr) mutations, which
      allows the parasite to colonize the R gene plant. Scientists hope to make R genes
      more durable by stacking them in a single cultivar. However, stacking assumes
      that R gene-mediated resistance has no fitness cost for the plant. We tested this
      assumption for wheat's resistance to Hessian fly, Mayetiola destructor (Say)
      (Diptera: Cecidomyiidae). Our study included ten plant fitness measures and four
      wheat genotypes, one susceptible, and three expressing either the H6, H9, or H13
      resistance gene. Because R gene-mediated resistance has two components, we
      measured two types of costs: the cost of the constitutively-expressed H gene,
      which functions in plant surveillance, and the cost of the downstream induced
      responses, which were triggered by Hessian fly larvae rather than a chemical
      elicitor. For the constitutively expressed Hgene, some measures indicated costs,
      but a greater number of measures indicated benefits of simply expressing the H
      gene. For the induced resistance, instead of costs, resistant plants showed
      benefits of being attacked. Resistant plants were more likely to survive attack
      than susceptible plants, and surviving resistant plants produced higher yield and
      quality. We discuss why resistance to the Hessian fly has little or no cost and
      propose that tolerance is important, with compensatory growth occurring after H
      gene-mediated resistance kills the larva. We end with a caution: Given that
      plants were given good growing conditions, fitness costs may be found under
      conditions of greater biotic or abiotic stress.

PMID- 21882710
TI  - Wheat curl mite resistance: interactions of mite feeding with wheat streak mosaic
      virus infection.
AB  - The majority of plant viruses are dependent on arthropod vectors for spread
      between plants. Wheat streak mosaic virus (family Potyviridae, genus
      Tritimovirus, WSMV) is transmitted by the wheat curl mite, Aceria tosichella
      Keifer, and this virus and vector cause extensive yield losses in most major
      wheat (Triticum aestivum L.)-growing regions of the world. Many cultivars in use
      are susceptible to this vector-virus complex, and yield losses of 10-99% have
      been documented. wheat curl mite resistance genes have been identified in goat
      grass, Aegilops tauschii (Coss) Schmal., and transferred to hexaploid wheat, but
      very few varieties contain effectively wheat curl mite resistance, due to
      virulent wheat curl mite populations. However, wheat curl mite resistance remains
      an effective strategy to reduce losses due to WSMV. The goal of our project was
      to identify the most effective, reproducible, and rapid method for assessing
      wheat curl mite resistance. We also wanted to determine whether mite resistance
      is affected by WSMV infection, because the pathogen and pest commonly occur
      together. Single and group wheat curl mite infestations produced similar amounts
      of leaf rolling and folding on wheat curl mite-susceptible wheat varieties that
      were independent of initial wheat curl mite infestation. This finding will allow
      accurate, efficient, large-scale screening of wheat germplasm for wheat curl mite
      resistance by infesting plants with sections of wheat leaf tissue containing
      mixed stages of wheat curl mite. The wheat curl mite-resistant breeding line
      'OK05312' displayed antibiosis (reduced wheat curl mite population development).
      The effect of WSMV infection on wheat curl mite reproduction was genotype
      dependent. Mite populations increased on infected wheat curl mite- and WSMV
      susceptible plants compared with uninfected plants, but WSMV infection had no
      significant effect on wheat curl mite populations on resistant plants. OK05312 is
      a strong source of wheat curl mite resistance for wheat breeding programs.

PMID- 21882711
TI  - Efficacy of heat treatment for disinfestation of concrete grain silos.
AB  - Field experiments were conducted in 2007 and 2008 to evaluate heat treatment for
      disinfestations of empty concrete elevator silos. A Mobile Heat Treatment Unit
      was used to introduce heat into silos to attain target conditions of 50 degrees C
      for at least 6 h. Ventilated plastic containers with a capacity of 100 g of
      wheat, Triticum aestivum L., held Rhyzopertha dominica (F.) (Coleoptera:
      Bostrichidae) and Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae).
      Polyvinyl chloride containers with a capacity of 300 g of wheat held adults of
      Liposcelis corrodens (Heymons) (Psocoptera: Liposcelididae) and Liposcelis
      decolor (Pearman), which were contained in 35-mm Petri dishes within the grain.
      Containers were fastened to a rope suspended from the top of the silo at depths
      of 0 m (just under the top manhole), 10 m, 20 m, and 30 m (silo floor). When the
      highest temperature achieved was approximately 50 degrees C for 6 h, parental
      mortality ofR. dominica and T. castaneum, and both psocid species was 98-100%.
      Progeny production of R. dominica occurred when there was parental survival, but
      in general R. dominica seemed less impacted by the heat treatment than T.
      castaneum. There was 100% mortality of L. corrodens at all depths in the heat
      treatments but only 92.5% mortality for L. decolor, with most survivors located
      in the bioassay containers at the top of the silo. Results show wheat kernels may
      have an insulating effect and heat treatment might be more effective when used in
      conjunction with sanitation and cleaning procedures.

PMID- 21882712
TI  - Freeze mortality characteristics of the mold mite Tyrophagus putrescentiae, a
      significant pest of stored products.
AB  - The mold mite Tyrophagus putrescentiae (Shrank) is a common pest of stored food
      products. Until recently, commodity and facility treatments have relied on
      acaricides and fumigants to control this mite. However, T. putrescentiae will
      cause infestations in areas where acaricide or fumigant use may be restricted,
      prohibited, or highly impractical. Because temperature is an essential factor
      that limits the survival of arthropod species, extreme temperatures can be
      exploited as an effective method of control. Making low-temperature treatments
      reliable requires better temperature-time mortality estimates for different
      stages of this mite. This was accomplished by exposing a representative culture
      (eggs, nymphs, and adults) of noncold-acclimated T. putrescentiae to subfreezing
      temperatures to determine their supercooling points (SCPs), lower lethal
      temperatures (LLTs) and lethal times (LTimes) at set temperatures. The results
      indicate that the adult and nymphal stages of T. putrescentiae are freeze
      intolerant; based on 95% CIs, the adult LLT90 of -22.5 degrees C is not
      significantly different from the SCP of -24.2 degrees C and the nymphal LLT90 of 
      28.7 degrees C is not significantly different from the SCP of -26.5 degrees C.
      The egg stage seems to be freeze tolerant, with an LLT90 of -48.1 degrees C,
      significantly colder by approximately 13.5 degrees C than its SCP of -35.6
      degrees C. The LTime demonstrates that 90% of all mite stages of T. putrescentiae
      can be controlled within commodity or packaged product by freezing to -18 degrees
      C for 5 h. By achieving the recommended time and temperature exposures, freezing
      conditions can be an effective way of controlling mites and reducing chronic
      infestations.

PMID- 21882713
TI  - Evaluating light attraction to increase trap efficiency for Tribolium castaneum
      (Coleoptera: Tenebrionidae).
AB  - The red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae),
      is a major coleopteran pest in flour mills and storage facilities. An aggregation
      pheromone has been identified for this pest; however, the pheromone is of limited
      value for population monitoring. To develop more efficient methods to monitor
      this pest, experiments were conducted to determine whether light functioned as an
      attractant for the red flour beetle. Light-emitting diodes (LEDs) of various
      wavelengths were examined as light sources because they produce bright, narrow
      light spectra. A comparison of responses to light spectra across the visible and
      UV regions of the electromagnetic spectrum indicated that the beetle was most
      attracted to near UV LED at a 390 nm dominant wavelength. The use of LEDs in
      competitive laboratory experiments resulted in a 20% capture of released beetles,
      compared with a 1% capture with the aggregation pheromone alone. Even more
      beetles were captured with a combination of LEDs and commercially available
      chemical lures in traps. LEDs can easily be added onto existing trap designs or
      new traps can be designed to take full advantage of positive phototaxis.

PMID- 21882714
TI  - Development, survival, and reproduction of the psocid Liposcelis yunnaniensis
      (Psocoptera: Liposcelididae) at constant temperatures.
AB  - We investigated the effects often constant temperatures (20.0, 22.5, 25.0, 27.5,
      30.0, 32.5, 35.0, 37.5, 39.0, and 41.0 degrees C) on the development, survival,
      and reproduction of the psocid Liposcelis yunnaniensis Li & Li (Psocoptera:
      Liposcelididae). At 39.0 and 41.0 degrees C, none of individuals could develop
      successfully or reproduce. From 20 to 37.5 degrees C, the development period from
      egg to adult ranged from 64.3 d at 20 degrees C to 16.1 d at 35 degrees C. The
      lower developmental threshold for egg, nymph, and combined immature stages were
      estimated at 15.08, 15.13, and 14.77 degrees C, respectively. After emergence the
      females went through a preoviposition period that ranged from 18.5 d at 22.5
      degrees C to 3.11 d at 35 degrees C, whereas it was 16.3 d at 20 degrees C.
      Liposcelis yunnaniensis produced most eggs at 35 degrees C and the fewest at 22.5
      degrees C. The population reared at 35 degrees C had the highest intrinsic rate
      of increase, shorter mean generation time, and shortest population doubling time
      compared with other temperatures. According to Weibull frequency distribution, L.
      yunnaniensis reared at all the temperatures had type III survivorship curves (c <
      1.0). Based on life-table parameter estimations, we suggest that optimum range of
      temperatures for this species is from 25 to 37.5 degrees C. These data give us
      useful information on population biology of L. yunnaniensis and can be used to
      better manage this species.

PMID- 21882715
TI  - Contact toxicity, feeding reduction, and repellency of essential oils from three
      plants from the ginger family (Zingiberaceae) and their major components against
      Sitophilus zeamais and Tribolium castaneum.
AB  - The essential oils from rhizomes of Alpinia conchigera Griff, Zingiber zerumbet
      Smitt, Curcuma zedoaria (Berg.) Roscoe; their major compounds (camphene, camphor,
      1,8-cineole, alpha-humulene, isoborneol, alpha-pinene, beta-pinene and terpinen-4
      ol); and synthetic essential oils comprised of mixtures of major pure compounds
      in the same ratios as the extracted essential oils were tested for contact,
      feeding reduction, and repellency against Sitophilus zeamais Motschulsky and
      Tribolium castaneum (Herbst) adults. Via topical applications, the three
      extracted oils had similar toxicity against S. zeamais (LD50 fiducial limits: 18
      24 microg oil/mg insect). T. castaneum had similar sensitivity to all three oils
      (35-58 microg/mg), and it was less sensitive than S. zeamais. The LD50 values of
      synthetic A. conchigera and synthetic Z. zerumbet oils were similar to those of
      their corresponding extracted essential oils. The synthetic C. zedoaria oils
      showed lower contact toxicity than the extracted C. zedoaria oils to both
      insects. Sitophilus zeamais and T. castaneum were sensitive to terpinen-4-ol and
      isoborneol in contact toxicity tests. In antifeedant tests, the three extracted
      oils were able to decrease the consumption of flour disks, especially Z. zerumbet
      oils, whereas both insect species could feed on the flour disks treated with
      three synthetic essential oils. Only terpinen-4-ol deterred feeding in both
      insects. In repellency tests, A. conchigera oils at highest concentration
      repelled S. zeamais and T. castaneum. None of the synthetic essential oils
      repelled S. zeamais (315 microl/cm2) and T. castaneum (31 microl/cm2) Only
      terpinen-4-ol showed repellent activity against both insects.

PMID- 21882716
TI  - Perception as interacting psychophysical functions. Could the configuring of
      features replace a specialised receptor?
AB  - This paper illustrates how perception is achieved through interactions among the
      psychophysical functions of judged features of an object. The theory is that the
      perceiver places processed features in a multidimensional space of discriminal
      processes. Each dimension is scaled in units of discrimination performance. The
      zero coordinate of each feature is its level in an internal standard (norm)
      established by previous experience of that category of object in context.
      Experiments are reported which show that one, two, or three concurrent single
      featured objects matched the multiple features of another object in two ways.
      Either stimulation from the two objects had discrimination distances from norm
      that added, or the stimulation by one object was processed through a concept
      describing stimulation by the other object. It follows that, in this case,
      perception via a receptor for the multi-featured object can be replaced by a
      point of balance among receptors for each single feature. The object with its own
      receptor is the gustatory stimulant L-glutamic acid as its monosodium salt. The
      features that stimulate diverse gustatory receptors of their own are sodium
      chloride, citric acid, sucrose, and caffeine. A more complex approach to
      dimensional coding was developed earlier for photoreceptors in colour judgments.
      The present approach is modality independent, mathematically simple, and
      economical in experimental data.

PMID- 21882717
TI  - Action-specific effects underwater.
AB  - Action-specific effects on perception are apparent in terrestrial environments.
      For example, targets that require more effort to walk, jump, or throw to look
      farther away than when the targets require less effort. Here, we examined whether
      action-specific effects would generalize to an underwater environment. Instead,
      perception might be geometrically precise, rather than action-specific, in an
      environment that is novel from an evolutionary perspective. We manipulated ease
      to swim by giving participants swimming flippers or taking them away. Those who
      estimated distance while wearing the flippers judged underwater targets to be
      closer than did participants who had taken them off. In addition, participants
      with better swimming ability judged the targets to be closer than did those with
      worse swimming ability. These results suggest perceived distance underwater is a
      function of the perceiver's ability to swim to the targets.

PMID- 21882718
TI  - Object-position binding in visual short-term memory for sequentially presented
      unfamiliar stimuli.
AB  - The effect of spatial position on visual short-term memory (VSTM) for
      sequentially presented objects has been investigated relatively little, despite
      the fact that vision in natural environments is characterised by frequent changes
      in object position and gaze location. We investigated the effect of reusing
      previously examined spatial positions on VSTM for object appearance. Observers
      performed a yes-no recognition task following a memory display comprising briefly
      presented 1/f noise discs (ie possessing spectral properties akin to natural
      images) shown sequentially at random coordinates. At test, single stimuli were
      presented either at original spatial positions, new positions, or at a fixed
      central position. Results, interpreted in terms of appearance and position
      preview effects, indicate that, where original spatial positions were reused at
      test, memory performance was elevated by more than 25%, despite that spatial
      position was task-irrelevant (in the sense that it could not be used to
      facilitate a correct response per se). This study generalises object-spatial
      position binding theory to a sequential display scenario in which the influences
      of extrafoveal processing, spatial context cues, and long-term memory support
      were minimised, thereby eliminating the hypothesis that object priming is the
      principal cause of the 'same-position advantage' in VSTM.

PMID- 21882719
TI  - Different signals of personality and health from the two sides of the face.
AB  - Previous studies demonstrate that people with different personality traits have
      different-looking faces. We investigated whether personality and health
      information are differently signalled by the two hemifaces. Using composite
      images created from women with high and low scores on health and personality
      dimensions, we investigated discrimination accuracy with original and mirrored
      hemifaces. By comparing discrimination accuracy for particular types of hemiface,
      we address issues regarding both the location of information signals and how
      these signals are conveyed. From the hemiface stimuli, participants could
      accurately identify three of the Big Five traits, along with health. We found
      differences in which hemiface could be more accurately identified, depending on
      the expressed trait. Emotional stability and health were more accurately
      discriminated from the right hemiface, while extraversion showed higher accuracy
      from the left hemiface. We found evidence for differences between hemifaces
      related to both directional asymmetries and to other information content.
      Finally, our results also address ongoing debate about which side of the face is
      more attractive, as we found attractiveness differences between hemifaces
      depended upon the personality trait most clearly expressed.

PMID- 21882721
TI  - Haptic object recognition: how important are depth cues and plane orientation?
AB  - Raised-line drawings of familiar objects are very difficult to identify with
      active touch only. In contrast, haptically explored real 3-D objects are usually
      recognised efficiently, albeit slower and less accurately than with vision. Real
      3-D objects have more depth information than outline drawings, but also extra
      information about identity (eg texture, hardness, temperature). Previous studies
      have not manipulated the availability of depth information in haptic object
      recognition whilst controlling for other information sources, so the importance
      of depth cues has not been assessed. In the present experiments, people named
      plastic small-scale models of familiar objects. Five versions of bilaterally
      symmetrical objects were produced. Versions varied only in the amount of depth
      information: minimal for cookie-cutter and filled-in outlines, partial for
      squashed and half objects, and full for 3-D models. Recognition was faster and
      much more accurate when more depth information was available, whether exploration
      was with both hands or just one finger. Novices found it almost impossible to
      recognise objects explored with two hand-held probes whereas experts succeeded
      using probes regardless of the amount of depth information. Surprisingly, plane
      misorientation did not impair recognition. Unlike with vision, depth information,
      but not object orientation, is extremely important for haptic object recognition.

PMID- 21882720
TI  - Gaze patterns during identity and emotion judgments in hearing adults and deaf
      users of American Sign Language.
AB  - Deaf individuals rely on facial expressions for emotional, social, and linguistic
      cues. In order to test the hypothesis that specialized experience with faces can
      alter typically observed gaze patterns, twelve hearing adults and twelve deaf,
      early-users of American Sign Language judged the emotion and identity of
      expressive faces (including whole faces, and isolated top and bottom halves),
      while accuracy and fixations were recorded. Both groups recognized individuals
      more accurately from top than bottom halves, and emotional expressions from
      bottom than top halves. Hearing adults directed the majority of fixations to the
      top halves of faces in both tasks, but fixated the bottom half slightly more
      often when judging emotion than identity. In contrast, deaf adults often split
      fixations evenly between the top and bottom halves regardless of task demands.
      These results suggest that deaf adults have habitual fixation patterns that may
      maximize their ability to gather information from expressive faces.

PMID- 21882722
TI  - Labeling, identification, and recognition of wine-relevant odorants in expert
      sommeliers, intermediates, and untrained wine drinkers.
AB  - In this study we examined the development of wine expertise. We asked four groups
      -untrained wine drinkers, second- and third-level trainee sommeliers, and
      professional sommeliers--to engage in a range of olfactory tasks to assess
      perceptual and semantic aspects of expertise. These tasks included
      identification, recognition, and description of a range of domain-specific and
      common odour stimuli, including wines. Trainee sommeliers were significantly
      poorer at identification of wine-relevant odours than untrained wine drinkers and
      professional sommeliers. Trainee and professional sommeliers were, however,
      significantly better than untrained wine drinkers in a delayed matching-to-sample
      wine-recognition task, but not in the case of other odorous stimuli. The wine
      description task demonstrated a degree of skill, in terms of specificity and
      quantity of wine-relevant descriptors, as a function of expertise. These results,
      of one of the first studies of examining wine expertise by a cross-sectional
      developmental approach, indicate that perceptual aspects of expertise are
      probably rapidly acquired, being present even in the second- and third-level
      trainees, while semantic expertise is slower to develop, and may incur time for
      the identification of wine-specific odorants during training.

PMID- 21882723
TI  - Increment of the extinction illusion by long stimulation.
AB  - We quantitatively examined the effect of stimulus duration on the extinction
      illusion. A white disc was presented or not presented at an intersection of a
      grey grid (intersection configuration) or on a homogeneous background (background
      configuration). The extinction illusion was quantified as the subtraction of no
      disc responses in the background configuration (ie baseline) from no-disc
      responses in the intersection configuration, when the disc was presented.
      Experiment 1 showed a temporal effect: the extinction illusion increased as
      stimulus duration increased; this temporal effect was observed when the disc was
      presented at 9 deg from the fixation point and when the stimulus duration was
      1000-6000 ms. Experiment 2 showed a visual field anisotropy: the extinction
      illusion occurred more frequently in the upper visual field than in the lower
      visual field, when the stimulus duration was 200 ms; the anisotropy was not
      observed when the stimulus duration was 6000 ms. Experiment 3 showed an alley
      length effect: when the grid alley was long, the extinction illusion occurred
      more frequently in the 6000 ms condition than in the 200 ms condition; the
      temporal effect was not observed when the grid alley was short. These results
      suggest that the temporal effect of the extinction illusion might be due to
      perceptual filling-in of luminance information of the grid alley.

PMID- 21882724
TI  - Relative influences of lightness and facial morphology on perceived race.
AB  - In a recent study (Brooks and Gwinn, 2010 Perception 39 1142-1145), the lightness
      contrast illusion was employed to study the influences of skin tone and facial
      morphology on race perception. The findings were rather counterintuitive: they
      suggested that skin tone does not play a major role in racial categorisation. To
      investigate this further, we used a parametric paradigm including five lightness
      levels, five morphing levels, and two face orientations. In accordance with
      Brooks and Gwinn, we found that race categorisation of African-American and
      Caucasian faces by Caucasian participants relied mainly on morphological cues.
      However, the relative influence of lightness increased when morphological
      information was ambiguous and when the faces were upside down. Overall, the
      results point to a flexible multicue-based mechanism underlying race perception.

PMID- 21882725
TI  - Me, myself, and I: different recognition rates for three photo-IDs of the same
      person.
AB  - In all contemporary societies, photo-identity documents are used routinely for
      person identification, but this process is surprisingly fallible. Here we show
      that this problem is not limited to the identification of specific photographs of
      a person, but transcends three identity cards of the same person with different
      images. These identity cards varied substantially from each other in how well
      they could be recognised but identification rates were generally poor. We also
      present a potential solution to this problem by demonstrating that person
      identification can be improved when several photographs of the same person are
      made available.

PMID- 21882726
TI  - Flashed face distortion effect: grotesque faces from relative spaces.
AB  - We describe a novel face distortion effect resulting from the fast-paced
      presentation of eye-aligned faces. When cycling through the faces on a computer
      screen, each face seems to become a caricature of itself and some faces appear
      highly deformed, even grotesque. The degree of distortion is greatest for faces
      that deviate from the others in the set on a particular dimension (eg if a person
      has a large forehead, it looks particularly large). This new method of image
      presentation, based on alignment and speed, could provide a useful tool for
      investigating contrastive distortion effects and face adaptation.

PMID- 21882727
TI  - Waiting can be so hard.

PMID- 21882728
TI  - Marion's message. Working internationally: how to identify (and avoid) cultural
      imperialism.

PMID- 21882729
TI  - Allowing birth to be birth: re-mystifying second stage.

PMID- 21882730
TI  - Midwifing second stage.

PMID- 21882731
TI  - Prenatal vitamins: helpful or harmful?

PMID- 21882733
TI  - An exploration of unusally long second stage: redefining normal.

PMID- 21882732
TI  - Birth from baby's view.

PMID- 21882734
TI  - Understanding stages of labour after the paradigm shift.

PMID- 21882735
TI  - A VBAC in the kitchen.

PMID- 21882736
TI  - Second stage evolution.

PMID- 21882737
TI  - Getting pushy.

PMID- 21882738
TI  - Vitamin K; did nature get it right?

PMID- 21882739
TI  - Labor pattern and management during a prolonged second stage.

PMID- 21882740
TI  - Getting to second stage.

PMID- 21882741
TI  - Why wait until second stage?

PMID- 21882742
TI  - An overview of upright positions during second stage labor.

PMID- 21882743
TI  - How to support the autonomy of motherbaby in second stage of waterbirth.

PMID- 21882744
TI  - Father's day surprise.

PMID- 21882746
TI  - New birth paradigm.

PMID- 21882745
TI  - Birth and freedom.

PMID- 21882747
TI  - Policy changes in the UK.

PMID- 21882748
TI  - Transitional phase of a new childbirth paradigm: Slovenia on the crossroad.

PMID- 21882749
TI  - In search of hope for Rita.

PMID- 21882750
TI  - Three stories, two continents, one birth journey.

PMID- 21882751
TI  - Planned homebirth in Brazil with nurse-midwife assistance: perceptions of women
      and companions.

PMID- 21882752
TI  - Due for change?

PMID- 21882753
TI  - The story of Bridget Shevlane: a labor of love.

PMID- 21882754
TI  - More meaning for meaningful use?

PMID- 21882755
TI  - Reshaping healthcare at the clinical boratory level.

PMID- 21882756
TI  - LC-MS/MS in the clinical lab: strengths, applications, challenges.

PMID- 21882757
TI  - Full micro-lab automation mass spectroscopy: fast and reliable microorganism
      identification within reach.

PMID- 21882758
TI  - The 'pneu' in pneumatic tube systems.

PMID- 21882759
TI  - Take steps to prevent spoliation when using electronic records.

PMID- 21882760
TI  - Molecular detection of toxigenic cdifficile: toxin A or B gene?

PMID- 21882761
TI  - Always be ready: biohazard or pandemic, preparation is key.

PMID- 21882762
TI  - Bacterial biofilms and HAIs.

PMID- 21882763
TI  - A new reflex testing algorithm for syphilis screening.
AB  - The laboratory diagnosis of syphilis is made possible through using a combination
      of non-treponemal and treponemal tests. The use of only one type of test when
      positive, without a confirmatory test being performed, is not sufficient for
      diagnosis because of false-positive results due to different medical conditions.
      All test results must be interpreted carefully, together with the patient's
      clinical history and symptoms, to arrive at a clinical diagnosis of syphilis.

PMID- 21882764
TI  - Biocare Medical CEO touts multiplex solution to solve complex cases.

PMID- 21882765
TI  - MAJOR milestone. Project brings two operations together under one roof.

PMID- 21882766
TI  - Baby watch. Ensuring proper operation of electronic infant-protection systems.

PMID- 21882767
TI  - Never again. The role of design in preventing 'never events'.

PMID- 21882768
TI  - Future directions. Vendors roll out the next generation of health care signage.

PMID- 21882769
TI  - Outpatient options. A look at the changing ambulatory care facility.

PMID- 21882770
TI  - Silent menace. C. difficile and its threat to health care facilities.

PMID- 21882771
TI  - A new paradigm for military humanitarian medical operations: mission-generic
      metrics.
AB  - OBJECTIVE: We report the history of military humanitarian medical operations,
      define the current science of process and outcome evaluation, and propose a set
      of generic metrics for monitoring and evaluation in military humanitarian
      operations. METHODS: We comprehensively reviewed the unclassified literature and
      used our own experiences in military humanitarian activities. RESULTS: Our
      literature review shows that efforts to evaluate the relative quality or cost
      effectiveness of military humanitarian missions have been largely unsuccessful.
      In response to this finding, the authors propose a monitoring and evaluation
      checklist system with generic metrics, which are broadly applicable but also can
      be customized specifically for the user. CONCLUSIONS: Military humanitarian
      operations can provide substantial security value to their many different
      stakeholders. Refinement of our proposed mission-generic metrics list is one
      method to measure performance and relative quality. Better assessment of outcomes
      can clarify decisions about the utilization of limited military medical
      humanitarian funds and personnel.

PMID- 21882772
TI  - The supply of pharmaceuticals in humanitarian assistance missions: implications
      for military operations.
AB  - In this article, we provide an overview of key international guidelines governing
      the supply of pharmaceuticals during disasters and complex emergencies. We review
      the World Health Organization's guidelines on pharmaceutical supply chain
      management and highlight their relevance for military humanitarian assistance
      missions. Given the important role of pharmaceuticals in addressing population
      health needs during humanitarian emergencies, a good understanding of how
      pharmaceuticals are supplied at the local level in different countries can help
      military health personnel identify the most appropriate supply options.
      Familiarity with international guidelines involved in cross-border movement of
      pharmaceuticals can improve the ability of military personnel to communicate more
      effectively with other actors involved in humanitarian and development spheres.
      Enhancing the knowledge base available to military personnel in terms of existing
      supply models and funding procedures can improve the effectiveness of
      humanitarian military operations and invite policy changes necessary to establish
      more flexible acquisition and funding regulations.

PMID- 21882773
TI  - Finally "deliberate by design": milestones in the delivery of health care for
      U.S. military family members.
AB  - The development of medical care for U.S. military families and retirees was
      serendipitous, a fortunate accident. The formal development of military family
      medical care required the evolution of three factors: the emergence of a standing
      army, frontiers to guard, and a peace to defend. These factors were first
      realized in the late 19th Century, and beginning at that point in U.S. history,
      seven key years highlight major milestones in the history of military family
      member medical care. At the same time, these years exemplify changing ideas of
      disease and of health care and how the physical design of clinics and hospitals
      reflects and impacts these ideas. The Fort Belvoir Community Hospital, which
      opens in 2011, exemplifies the Nation's best example of green hospital
      construction, patient and family centered care, and evidence-based design in a
      Culture of Excellence that demonstrates that military family medical care is
      finally "deliberate by design."

PMID- 21882774
TI  - Deployment-related testing and treatment for latent tuberculosis infection, Part
      I.
AB  - Current Topics in Military Tropical Medicine is a Continuing Medical Education
      series, which updates military medical personnel on questions related to clinical
      practice while deployed. This issue is Part I of a two-part series on the
      approach to decision to test, testing and management of latent tuberculosis
      infection. A representative case is explored in both parts to highlight how to
      approach service members and their units with regards to latent tuberculosis
      infection screening and intervention.

PMID- 21882775
TI  - Bringing in the Bystander in-person prevention program to a U.S. military
      installation: results from a pilot study.
AB  - OBJECTIVES: This pilot study describes an evaluation of the Bringing in the
      Bystander (BITB) in-person program conducted with United States Army Europe
      personnel. METHODS: The sample was comprised of 394 soldiers (29% participated in
      and 71% had not participated in the BITB program). Data were analyzed 4V2 months
      after the program was presented. RESULTS: Compared to the soldiers who did not
      participate in the program, soldiers who participated in the program were
      significantly more likely to report that they had engaged in one or more of the
      117 behaviors, that they had helped an acquaintance or a stranger, and that they
      had taken action when they saw sexual assault or stalking occurring, about to
      occur or after it had occurred. CONCLUSIONS: The results indicate that with
      thoughtful and appropriate modifications, the BITB in-person prevention program,
      initially developed for a college audience, can be transferred to a military
      audience.

PMID- 21882776
TI  - Complex regional pain syndrome in an 8-year-old female with emotional stress
      during deployment of a family member.
AB  - INTRODUCTION: This pediatric case of complex regional pain syndrome (CRPS)
      illustrates the need to expand the typical age range and raise awareness of the
      psychological impact military deployment may have on its development. CASE: An
      emotional 8-year-old female, with a recently deployed father, presented with left
      foot pain. Over an 11-week-period, she developed symptoms, signs, and radiologic
      findings consistent with CRPS. DISCUSSION: Pediatric CRPS is characterized by
      ecchymosis, edema, allodynia, mottling, and abnormal hair growth in the region of
      pain after minor trauma. It occurs predominately in adolescent females, mainly
      affects the lower limbs, and is associated with psychological stressors. This
      patient with CRPS presents several years younger than what is commonly described
      in the literature in the stressful setting of a deployed parent. CONCLUSION: CRPS
      can occur in younger than expected age ranges of children who experience the
      unique emotional stressor of a deployed family member.

PMID- 21882777
TI  - Sleep disruptions among returning combat veterans from Iraq and Afghanistan.
AB  - BACKGROUND: Post-traumatic stress disorder (PTSD) and traumatic brain injury
      (TBI) are common injuries among returning combat veterans from the wars in Iraq
      and Afghanistan. Although these combat injuries have been associated with
      increased sleep disruption, little is known about the nature and specificity of
      sleep problems within these common injury categories. METHOD: A retrospective
      chart review of 69 consecutive referrals to the Waiter Reed Army Medical Center
      sleep clinic was conducted. All cases were active duty soldiers who had recently
      returned from combat deployment in Iraq or Afghanistan. Data from
      polysomnographically (PSG) recorded sleep stages, sleepiness scales, and
      documented medical diagnoses were extracted from medical records. Sleep data were
      compared across diagnoses of PTSD, TBI, and other clinical conditions. RESULTS:
      As expected, clinical sleep disturbances, including rates of obstructive sleep
      apnea, excessive awakenings, daytime sleepiness, and hypoxia, were high for the
      sample as a whole. However, no differences across diagnostic groups were found.
      Differences were observed, however, on PSG measures of sleep quality, suggesting
      more frequent arousals from sleep among patients with PTSD and greater slow wave
      sleep among those with TBI. Except for REM latency, medication status had
      virtually no effect on sleep variables. CONCLUSIONS: Among recently redeployed
      combat veterans, clinically significant sleep disturbances and problems with
      sleep-disordered breathing are common but nonspecific findings across primary
      diagnoses of PTSD, TBI, major depression, and anxiety disorder, whereas more
      subtle differences in sleep architecture and arousals as measured by overnight
      PSG recordings were modestly, but significantly, effective at distinguishing
      among the diagnostic groups.

PMID- 21882778
TI  - Anaphylaxis: assessment of a disease-based military medical standard.
AB  - Although widespread, the use of disease-based employment medical standards is
      poorly understood or researched. A probabilistic model and threshold value are
      developed and applied to a military (Canadian Forces [CF]) medical standard for
      anaphylaxis. Frequency estimates of prevalence, occurrence, and impairing
      reactions are determined from the literature for military applicants and from
      medical chart review of military members identified by prescriptions for self
      administered epinephrine. The prevalence of prescriptions is 1.13% (CI 1.05,
      1.22) and 0.86% (CI 0.72, 1.00) in the CF Regular Force and applicant
      populations, respectively. The proposed model predicts the annual risk of an
      impairing allergic reaction in the CF population ranges from 0.1% to 0.16%/year,
      well below the proposed threshold of 0.5%. The majority of this risk arises from
      new cases and not recurrences. Requirement for care increases with recurrence.
      This model allows a useful method of disease-based medical standard review.

PMID- 21882780
TI  - Diagnoses and mechanisms of musculoskeletal injuries in an infantry brigade
      combat team deployed to Afghanistan evaluated by the brigade physical therapist.
AB  - Musculoskeletal injuries are the most common cause for disability in deployed
      environments. Current research is limited to body region affected by the injury.
      OBJECTIVE: To determine the prevalence of musculoskeletal diagnoses and
      mechanisms of injury (MOI) as well as associations to specific Military
      Occupational Specialties (MOS) in a deployed Brigade Combat Team (BCT). METHODS:
      Data collected on 3,066 patient encounters by the Brigade Combat Team physical
      therapist over 15 months were analyzed using descriptive statistics and X2 tests.
      RESULTS: Mechanical low back pain was the most common diagnosis (19%), whereas
      overuse was the most prevalent MOI (22%). The Infantry MOS was significantly
      associated with meniscal tears and pre-existing injuries, the Maintenance MOS
      with contusions, Signal and Transportation MOSs with weight lifting injuries, and
      the Administrative MOS with running injuries. CONCLUSION: Different MOSs are
      preferentially susceptible to different diagnoses and MOIs. Therefore, different
      injury prevention strategies may be needed across occupations.

PMID- 21882779
TI  - The relationship between Gulf War illness, brain N-acetylaspartate, and post
      traumatic stress disorder.
AB  - A previous study (Haley RW, Marshall WW, McDonald GG, Daugherty MA, Petty F,
      Fleckenstein JL: Brain abnormalities in Gulf War syndrome: evaluation with 1H MR
      spectroscopy. Radiology 2000; 215: 807-817) suggested that individuals with Gulf
      War Illness (GWI) had reduced quantities of the neuronal marker N-acetylaspartate
      (NAA) in the basal ganglia and pons. This study aimed to determine whether NAA is
      reduced in these regions and to investigate correlations with other possible
      causes of GWI, such as psychological response to stress in a large cohort of Gulf
      War veterans. Individuals underwent tests to determine their physical and
      psychological health and to identify veterans with (n=81) and without (n=97) GWI.
      When concentrations of NAA and ratios of NAA to creatine- and choline-containing
      metabolites were measured in the basal ganglia and pons, no significant
      differences were found between veterans with or without GWI, suggesting that GWI
      is not associated with reduced NAA in these regions. Veterans with GWI had
      significantly higher rates of post-traumatic stress disorder, supporting the idea
      that GWI symptoms are stress related.

PMID- 21882781
TI  - Association between barracks type and acute respiratory infection in a gender
      integrated Army basic combat training population.
AB  - BACKGROUND: Acute respiratory infections (ARIs) are the leading cause of acute
      morbidity and lost work time in the United States. Few studies have looked at
      building design and transmission of ARIs. OBJECTIVES: This study explores the
      association of ventilation design, room occupancy numbers, and training week with
      ARI rates in Army Basic Combat Training barracks. METHODS: This observational
      study captured the overall incidence of ARI in a cohort of 16,258 individuals
      attending basic combat training at Fort Jackson, South Carolina. RESULTS: ARI
      risk was higher among trainees living in the 60-person room barracks compared
      with those living in 8-person rooms, which increased rapidly for the first few
      weeks of training and then declined to baseline. CONCLUSIONS: Findings support
      direct contact as primary ARI transmission mode in this study population based on
      observed lower ARI risk in smaller room barracks and similar risk in large room
      barracks despite heating, ventilation, and air conditioning system variability.

PMID- 21882782
TI  - Assessment of changes in mental health conditions among sailors and marines
      during postdeployment phase.
AB  - Previous research regarding the mental health ramifications of military
      deployments focused on the U.S. Army population. As part of its deployment health
      surveillance mission, Navy and Marine Corps Public Health Center conducted a
      study of the Department of Navy population to identify reported mental health
      effects associated with Operation Iraqi Freedom, describe mental health care
      utilization by returning service members previously deployed in support of
      Operation Iraqi Freedom, and examine the relationships between self-identified
      risks and provider referral practices. Despite a considerable number of self
      reported mental health concerns, referral for mental health consultations and
      health care utilization were rare. The psychological well-being of service
      members is essential to the military's optimum functionality and operational
      readiness; therefore, continued research in this area has significant bearing on
      future force health protection efforts. Additionally, this study highlights the
      need for further research on deployment-related mental health concerns.

PMID- 21882783
TI  - Self-reported physical activity and preaccession fitness testing in U.S. Army
      applicants.
AB  - The Assessment of Recruit Motivation and Strength (ARMS) study evaluated a
      physical fitness screening test for Army applicants before basic training. This
      report examines applicants' self-reported physical activity as a predictor of
      objective fitness measured by ARMS. In 2006, the ARMS study administered a
      fitness test and physical activity survey to Army applicants during their medical
      evaluation, using multiple logistic regression for comparison. Among both men and
      women, "qualified" and "exceeds-body-fat" subjects who met American College of
      Sports Medicine adult physical activity guidelines were more likely to pass the
      fitness test. Overall, subjects who met physical activity recommendations,
      watched less television, and played on sports teams had a higher odds of passing
      the ARMS test after adjustment for age, race, and smoking status. This study
      demonstrates that self-reported physical activity was associated with physical
      fitness and may be used to identify those at risk of failing a preaccession
      fitness test.

PMID- 21882784
TI  - Pregnant soldiers' participation in physical training: a descriptive study.
AB  - This study identifies factors that influence U.S. Army soldiers' participation in
      the Pregnant Soldiers Wellness Program (PSWP), an exercise and wellness education
      program for soldiers who are either pregnant or in the postpartum period. A
      retrospective survey was administered prior to initial postpartum hospital
      discharge. Seventy-four soldiers who delivered babies at Womack Army Medical
      Center participated in this study. Of those surveyed, 66.2% of respondents
      participated in the PSWP, 59.5% were encouraged to participate by their provider.
      Few participants stated that the overall safety, structure, and quality of the
      PSWP were important factors contributing to their participation. Additionally,
      less than 20% reported that instructor's knowledge influenced their decision to
      participate in the PSWP. Most soldiers participated in the program for the health
      of their fetus and to quickly return to required Army weight standards. This
      study offers insights that will potentially increase the overall soldier
      participation rate in the PSWP, thus promoting greater health benefits for the
      pregnant soldier and increasing sustainment of force readiness.

PMID- 21882785
TI  - The introduction of extracorporeal membrane oxygenation to aeromedical
      evacuation.
AB  - OBJECTIVE: To review the principles of extracorporeal membrane oxygenation (ECMO)
      and to describe the recent advancements in ECMO technology that permit use of
      this rescue therapy for severe lung injury in combat casualties. METHODS/RESULTS:
      Lung protective ventilation has defined the state-of-the-art treatment for acute
      lung injury for more than a decade. Despite the benefits provided by a low tidal
      volume strategy, lung injury patients may experience deterioration in gas
      exchange to the point that other rescue interventions are needed or the patient
      succumbs to progressive respiratory failure. When this occurs in combat
      casualties, management of the patient in an austere environment and movement to
      definitive care become problematic. Recent advances in ECMO technology permit
      long-range transport of these critically ill casualties with greater physiologic
      reserve and potentially less mortality. CONCLUSIONS: Advances in ECMO technology
      now enable the stabilization and aeromedical evacuation of even the most
      critically ill combat casualties with severe lung injury.

PMID- 21882786
TI  - Retrospective case series of five nontraumatic deaths among U.S. Air Force basic
      military trainees (1997-2007).
AB  - INTRODUCTION: Basic military training is both physically and mentally demanding.
      New recruits represent a young and relatively healthy subpopulation of
      individuals, and premature mortality is rare. The purpose of this retrospective
      case series is to discuss the causes of nontraumatic deaths among U.S. Air Force
      Basic Military Trainees (BMTs) at Lackland Air Force Base in San Antonio, Texas.
      STUDY OBJECTIVE: The study objective is to describe the demographic,
      environmental, and clinical factors associated with nontraumatic deaths among
      BMTs. METHODS: Data were extracted from medical records and autopsy reports.
      RESULTS: During the time period of 1997 to 2007, there were 5 nontraumatic
      deaths. CONCLUSION: Implementation of new policies or revisions to existing
      policies has reduced the number of nontraumatic deaths in the U.S. Air Force BMT
      population.

PMID- 21882787
TI  - A rare case of anaphylaxis to bowel prep: a case report and review of the
      literature.
AB  - Polyethylene glycols (PEGs) are commonly utilized as a bowel prep prior to
      colonoscopy. They are generally well-tolerated, and reports of allergic reactions
      are rare. A recent search of the literature reveals only 4 prior reported cases
      of allergic reactions and only 1 other case of anaphylaxis. We report a second
      case of anaphylaxis following the ingestion of PEG solution, making this the
      fifth reported case of an allergic reaction to PEG bowel prep.

PMID- 21882788
TI  - Brugada syndrome unmasked by fever.
AB  - Brugada syndrome (BS) is a cardiac rhythm disturbance that predisposes patients
      to sudden cardiac death. Brugada is classically described with specific
      electrocardiographic (EKG) findings of ST elevation and right bundle branch block
      in precordial leads and is an often unrecognized contributor to sudden cardiac
      death. We present a case of BS with cyclic EKG findings in a febrile 20-year-old
      active duty, Vietnamese male who presented following a witnessed syncopal event.
      His classic findings of Brugada pattern on EKG demonstrated reversibility with
      clinical defervescence. In patients with a suggestive history, a normal EKG
      cannot definitively rule out BS as the Brugada pattern can be unmasked by stress,
      which in this case was represented by a pneumonia-induced fever.

PMID- 21882789
TI  - Performance of military tasks after clavicle plating.
AB  - Management of displaced midshaft clavicle fractures in the military, a largely
      shoulder-bearing population, is controversial. We aimed to report the military
      relevant functional outcomes after plate fixation. We performed a nested cross
      sectional analysis of active duty service members enrolled in an ongoing
      multicenter, randomized trial on clavicle plating. For this analysis, we included
      subjects with 26 months follow-up. Outcome measures included radiographic
      appearance, physical examination, a military-specific questionnaire, and
      validated shoulder surveys. Mean follow-up for 28 clavicle fractures was 13
      months. Union rate by 12 weeks was 93% (26/28). There was one case of soft tissue
      irritation requiring hardware removal. At latest follow-up, 75% of patients were
      satisfied; 68% had mild/no pain; 79% had full range of motion; 75% could perform
      push-ups; and 21% have deployed. For the majority of active duty personnel, rapid
      healing, return to military-specific tasks, and satisfaction with outcome are
      possible after plate fixation of clavicle fractures. However, approximately 25%
      report some functional limitations at 1 year.

PMID- 21882790
TI  - Prevalence of short partial thromboplastin times in a military treatment
      facility.
AB  - BACKGROUND: It was recently noted that a shortened activated partial
      thromboplastin time (aPTT) is associated with increased venous thromboembolic
      events. The prevalence of aPTT shortening remains unknown. METHODS: We conducted
      a retrospective analysis of aPTT results over a 2-month period. These results
      were not associated with patient clinical information. RESULTS: We obtained 3,376
      aPTT samples, which were analyzed in groups: <25.0, 25.0-35.0, and >35.0 seconds
      (two standard deviations from our laboratory's normal values). Eighty-six samples
      had aPTT<25 (8.5%), 2,026 samples between 25.0-35.0 (60.0%), and 1,064
      samples>35.0 (31.5%). Using chi-square goodness-of-fit, we found a clinically
      significant greater-than-expected prevalence of low aPTT levels (p<0.001).
      CONCLUSIONS: Although elevated aPTT samples could be explained by anticoagulation
      therapy, the reason for our findings of an increased number of low-aPTT studies
      remains unexplained. Further studies are required to investigate the clinical
      correlation of low aPTT levels and the incidence of venous thromboembolic events
      (VTEs) in our population.

PMID- 21882791
TI  - Heat strain during explosive ordnance disposal.
AB  - Bomb technicians perform their work while encapsulated in explosive ordnance
      disposal suits. Designed primarily for safety, these suits have an unintended
      consequence of impairing the body's natural mechanisms for heat dissipation.
      Consequently, bomb technicians are known to experience symptoms of heat illness
      while performing their work. This research provides the first field based
      analysis of heat strain in bomb technicians. Six participants undertook simulated
      operational tasks across 2 days of variable climate. All subjects demonstrated
      high levels of heat strain as evidenced by elevated heart rate, core body
      temperature, and physiological strain index. Participants also reported signs and
      symptoms associated with heat illness. These results were exacerbated by more
      intense physical activity despite being undertaken in a cooler environment. The
      universal experience of heat strain in this sample has significant implications
      for the health of bomb technicians and additional research examining methods to
      improve temperature regulation and performance is warranted.

PMID- 21882792
TI  - Negative-pressure pulmonary edema following a lateral internal sphincterotomy.
AB  - Negative-pressure pulmonary edema (NPPE) is an infrequent but known postoperative
      complication following endotracheal intubation and general anesthesia. We report
      a case of a healthy 24-year-old man requiring intensive care unit management for
      NPPE following a routine surgical procedure. This article discusses how rare but
      serious the complication of NPPE can be; it also describes the diagnosis,
      evaluation, and treatment from one institution's experience.

PMID- 21882793
TI  - Quality: the impact of rehabilitation nurses on patient outcomes.

PMID- 21882794
TI  - Communication: the key to effective interdisciplinary collaboration in the care
      of a child with complex rehabilitation needs.
AB  - Healthcare providers have the unique opportunity to provide care and treatment to
      patients with complex medical needs. They learn early in their careers that the
      care they provide doesn't just include the patient. Communication is essential
      across the continuum and involves multiple providers and the family. An
      interdisciplinary team facilitates a comprehensive plan for recovery and
      treatment. This case study centers on the interdisciplinary approach to the
      rehabilitation continuum of care across the spectrum and its effects on patient
      outcomes.

PMID- 21882795
TI  - Introduction of rehabilitation nursing concepts in Cambodia.
AB  - Cambodia is a poor country in Southeast Asia; 80% of its 14.1 million people are
      sustenance farmers (Central Intelligence Agency, 2006). Health Volunteers
      Overseas, based in Washington, DC, and Sihanouk Hospital of Hope in Phnom Penh,
      Cambodia, collaborate to recruit master's-prepared nurse educators to participate
      in volunteer teaching trips to enhance the knowledge and skill set of Cambodian
      staff nurses. A methodical series of steps were taken to develop a basic lecture
      series regarding the care of patients with brain and spinal cord injuries, taking
      into consideration Cambodian healthcare beliefs and health system resources. This
      article describes the processes used to develop the lectures and the realities of
      teaching on the other side of the world.

PMID- 21882796
TI  - Invest in the future: become a volunteer in your professional nursing
      organization.
AB  - In this article, volunteer activity in professional organizations is explored.
      Volunteerism is defined as the giving of a person's time, energy, and talent to
      organizations without monetary compensation. A combination of other-serving or
      altruistic and self-serving or instrumental factors motivates people to
      volunteer. Examples of these motivations include wanting to help others,
      contributing to an important cause, encouraging an action, belonging to a
      community that promotes a positive sense of self believing in a professional
      commitment to serve others, and being passionate about the things an organization
      brings to a profession. Challenges surrounding volunteerism are discussed in this
      article, and activities and opportunities for volunteer involvement in
      professional organizations are illustrated. Personal examples related to the
      Association of Rehabilitation Nurses (ARN) that detail the ways in which members
      can get involved also are highlighted.

PMID- 21882797
TI  - Nurses' experiences with bed exit alarms may lead to ambivalence about their
      effectiveness.
AB  - The literature reports conflicting evidence regarding the effectiveness of any
      single intervention, including bed exit alarms, in preventing falls. Yet bed exit
      alarms are widely used in healthcare settings as part of comprehensive fall
      prevention programs even though no large-scale randomized controlled trials have
      demonstrated their effectiveness. As a part of a quality improvement project, bed
      alarms were piloted on two nursing units in a Level I trauma center. Nurses'
      patterns of use, their experiences and beliefs about bed alarms, and the
      literature regarding bed exit alarms were explored. Alarms were used with
      confused and agitated patients who did not fall. Nurses said that bed alarms may
      have helped prevent falls, but, even with bed alarms in use, nurses still needed
      to monitor their patients hourly. The conflicting experiences of nurses using the
      alarms, combined with nurses' comments and literature both supporting and not
      supporting bed alarms, shed light on the dilemma nurses face when prioritizing
      safe patient care and the ambivalence some nurses experience regarding bed
      alarms.

PMID- 21882798
TI  - Therapeutic music and nursing in poststroke rehabilitation.
AB  - Individuals who experience stroke undergo a critical rehabilitation process with
      the aid of professionals including physical, occupational, and speech therapists,
      as well as primary care from nursing staff. However, the extent of the role that
      music can play in facilitating the rehabilitation process is unknown. Board
      certified music therapists are employed in several capacities within the
      rehabilitation environment. There is a need for nursing professionals in this
      area to better understand the role a music therapist may play and how they can
      assist clients in using music in a therapeutically beneficial way. The purpose of
      this article is to educate nurses about music therapy and provide evidence for
      the therapeutic use of music in the rehabilitation setting for victims of stroke.

PMID- 21882799
TI  - Case management in care of Turkish rheumatoid arthritis patients.
AB  - This study examined the effectiveness of a case management (CM) intervention in
      the care of patients with rheumatoid arthritis (RA) as a pilot study in a
      teaching hospital in Turkey. Two groups were compared with respect to disability,
      quality of life, cost, and patient satisfaction: RA patients who received CM plus
      usual nursing care and RA patients who received usual nursing care alone. All
      patients underwent follow-up interviews at 3 and 6 months after being discharged
      from the hospital. Disability scores were significantly better in the RA group
      receiving CM, but there were no significant differences between the two groups
      with regard to quality of life, patient satisfaction, and total healthcare costs.
      Using CM in the care of patients with RA may favorably affect disease-related
      outcomes.

PMID- 21882800
TI  - Delirium: a critical diagnosis for every member of the rehabilitation team.

PMID- 21882801
TI  - Urinary tract infections in patients admitted to rehabilitation from acute care
      settings: a descriptive research study.
AB  - The use of an indwelling urinary catheter comes with associated risks. At a
      hospital in southern California, nurses on the acute rehabilitation unit
      suspected their patients were arriving from acute care with undiagnosed urinary
      tract infections (UTIs). This descriptive research study quantified the incidence
      of UTI on admission to a rehabilitation unit and correlations with catheter use.
      During the study period, 132 patients were admitted to acute rehabilitation from
      an acute care setting, and 123 met criteria to participate in the study. Among
      participants, 12% had a UTI upon admission. Questionnaires examined nursing
      attitudes toward appropriate urinary catheter use and proactive catheter removal.
      The data revealed that nurses want to be involved in decisions about urinary
      catheter use and that medical/surgical and rehabilitation nurses agree strongly
      about advocating for patients with indwelling urinary catheters.

PMID- 21882802
TI  - Study of influential factors on oligosaccharide formation by fructosyltransferase
      activity during stachyose hydrolysis by Pectinex ultra SP-L.
AB  - The influence of reaction conditions for oligosaccharide synthesis from stachyose
      using a commercial enzymatic preparation from  Aspergillus aculeatus  (Pectinex
      Ultra SP-L) was studied. Oligosaccharides were analyzed by gas chromatography
      with flame ionization detection (GC-FID) and matrix-assisted laser
      desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS). Galactosyl
      melibiose (DP(3)) was synthesized as a result of fructosidase activity, whereas
      fructosyl-stachyose (DP(5)) and difructosyl-stachyose (DP(6)) were formed as a
      consequence of the fructosyltransferase activity of Pectinex Ultra SP-L. The
      optimal reaction conditions for the synthesis of penta- and hexasaccharides were
      60  degrees C, pH 5.5, 600 mg/mL stachyose, and 34 U/mL enzyme. Reaction time
      played an important role in oligosaccharide mixture composition constituted by
      20% DP(5), 0.7% DP(6), 55% stachyose, 21% galactosyl-melibiose, and 1%
      monosaccharides after 1 h and 16% DP(5), 4% DP(6), 27% stachyose, 44% galactosyl
      melibiose, and 2% monosaccharides after 3 h. In conclusion, stachyose could be
      used as a substrate for the enzymatic synthesis of new oligosaccharides that may
      open new opportunities in the development of future prebiotics.

PMID- 21882803
TI  - Mechanisms controlling the cellular accumulation of copper
      bis(thiosemicarbazonato) complexes.
AB  - Copper (Cu) bis(thiosemicarbazonato) metal complexes [Cu(II)(btsc)s] have unique
      tumor-imaging and treatment properties and more recently have revealed potent
      neuroprotective actions in animal and cell models of neurodegeneration. However,
      despite the continued development of Cu(II)(btsc)s as potential therapeutics or
      diagnostic agents, little is known of the mechanisms involved in cell uptake,
      subcellular trafficking, and efflux of this family of compounds. Because of their
      high lipophilicity, it has been assumed that cellular accumulation is through
      passive diffusion, although this has not been analyzed in detail. The role of
      efflux pathways in cell homeostasis of the complexes is also largely unknown. In
      the present study, we investigated the cellular accumulation of the Cu(II)(btsc)
      complexes Cu(II)(gtsm) and Cu(II)(atsm) in human neuronal (M17) and glial (U87MG)
      cell lines under a range of conditions. Collectively, the data strongly suggested
      that Cu(II)(gtsm) and Cu(II)(atsm) may be taken into these cells by combined
      passive and facilitated (protein-carrier-mediated) mechanisms. This was supported
      by strong temperature-dependent changes to the uptake of the complexes and the
      influence of the cell surface protein on Cu accumulation. We found no evidence to
      support a role for copper-transporter 1 in accumulation of the compounds.
      Importantly, our findings also demonstrated that Cu from both Cu(II)(gtsm) and
      Cu(II)(atsm) was rapidly effluxed from the cells through active mechanisms.
      Whether this was in the form of released ionic Cu or as an intact metal complex
      is not known. However, this finding highlighted the difficulty of trying to
      determine the uptake mechanism of metal complexes when efflux is occurring
      concomitantly. These findings are the first detailed exploration of the cellular
      accumulation mechanisms of Cu(II)(btsc)s. The study delineates strategies to
      investigate the uptake and efflux mechanisms of metal complexes in cells, while
      highlighting specific difficulties and challenges that need to be considered
      before drawing definitive conclusions.

PMID- 21882804
TI  - Probing the structure of the crystalline core of field-aligned, monodisperse,
      cylindrical polyisoprene-block-polyferrocenylsilane micelles in solution using
      synchrotron small- and wide-angle X-ray scattering.
AB  - The self-assembly of block copolymers in selective solvents represents a powerful
      approach to functional core-shell nanoparticles. Crystallization of the core can
      play a critical role in directing self-assembly toward desirable, nonspherical
      morphologies with low mean interfacial curvature. Moreover, epitaxial growth
      processes have been implicated in recent advances that permit access to
      monodisperse cylinders, cylindrical block comicelles with segmented cores and/or
      coronas, and complex hierarchical architectures. However, how the core-forming
      block crystallizes in an inherently curved nanoscopic environment has not been
      resolved. Herein we report the results of synchrotron small-angle X-ray
      scattering (SAXS) and wide-angle X-ray scattering (WAXS) studies of well-defined,
      monodisperse crystalline-coil polyisoprene-block-polyferrocenylsilane cylindrical
      micelles aligned in an electric field. WAXS studies of the aligned cylinders have
      provided key structural information on the nature of the PFS micelle core
      together with insight into the role of polymer crystallinity in the self-assembly
      of these and potentially related crystalline-coil block copolymers.

PMID- 21882805
TI  - Current-driven dynamics in molecular junctions: endohedral fullerenes.
AB  - We introduce a new paradigm for single molecule devices based on electronic
      actuation of the internal atom/cluster motion within a fullerene cage. By
      combining electronic structure calculations with dynamical simulations, we
      explore current-triggered dynamics in endohedrally doped fullerene molecular
      junctions. Inelastic electron tunneling through a Li atom localized resonance in
      the Au-Li@C(60)-Au junction initiates fascinating, strongly coupled 2D dynamics,
      wherein the Li atom exhibits large amplitude oscillation with respect to the
      fullerene wall and the fullerene cage bounces between the gold electrodes,
      slightly perturbed by the embedded atom motion. Implications to the fields of
      single molecule electronics and nanoelectromechanical systems are discussed.

PMID- 21882806
TI  - A new structural model of Abeta40 fibrils.
AB  - The amyloid fibrils of beta-amyloid (Abeta) peptides play important roles in the
      pathology of Alzheimer's disease. Comprehensive solid-state NMR (SSNMR)
      structural studies on uniformly isotope-labeled Abeta assemblies have been
      hampered for a long time by sample heterogeneity and low spectral resolution. In
      this work, SSNMR studies on well-ordered fibril samples of Abeta(40) with an
      additional N-terminal methionine provide high-resolution spectra which lead to an
      accurate structural model. The fibrils studied here carry distinct structural
      features compared to previous reports. The inter-beta-strand contacts within the
      U-shaped beta-strand-turn-beta-strand motif are shifted, the N-terminal region
      adopts a beta-conformation, and new inter-monomer contacts occur at the
      protofilament interface. The revealed structural diversity in Abeta fibrils
      points to a complex picture of Abeta fibrillation.

PMID- 21882807
TI  - Magnetically induced decrease in droplet contact angle on nanostructured
      surfaces.
AB  - We report a magnetic technique for altering the apparent contact angle of aqueous
      droplets deposited on a nanostructured surface. Polymeric tubes with embedded
      superparamagnetic magnetite (Fe(3)O(4)) nanoparticles were prepared via layer-by
      layer deposition in the 800 nm diameter pores of polycarbonate track-etched
      (PCTE) membranes. Etching away the original membrane yields a superparamagnetic
      film composed of mostly vertical tubes attached to a rigid substrate. We
      demonstrate that the apparent contact angle of pure water droplets deposited on
      the nanostructured film is highly sensitive to the ante situm strength of an
      applied magnetic field, decreasing linearly from 117 +/- 1.3 degrees  at no
      applied field to 105 +/- 0.4 degrees  at an applied field of approximately 500 G.
      Importantly, this decrease in contact angle did not require an inordinately
      strong magnetic field: a 15 degrees  decrease in contact angle was observed even
      with a standard alnico bar magnet. We interpret the observed contact angle
      behavior in terms of magnetically induced conformation changes in the film
      nanostructure, and we discuss the implications for reversibly switching
      substrates from hydrophilic to hydrophobic via externally tunable magnetic
      fields.

PMID- 21882808
TI  - Butterfly-shaped conjugated oligoelectrolyte/graphene oxide integrated assay for
      light-up visual detection of heparin.
AB  - A water-soluble pyrene-based butterfly shaped conjugated oligoelectrolyte (TFP)
      is synthesized and integrated with graphene oxide (GO) to form a label-free assay
      for heparin detection. Efficient fluorescence quenching occurs between TFP and GO
      because of strong electrostatic and pi-pi interactions, leading to nearly dark
      emission in the absence of analytes. Addition of heparin into TFP solution
      significantly minimizes the fluorescence quenching of GO toward TFP, which is
      less effective for the heparin analogues, such as hyaluronic acid and chondroitin
      4-sulfate. As a consequence, the solution emits strong yellow fluorescence only
      in the presence of heparin, which allows for light-up visual discrimination of
      heparin from its analogues. Moreover, the linear light-up response of the TFP/GO
      integrated assay enables heparin quantification in the range of 0-1.76 U/mL with
      a limit of detection of 0.046 U/mL, which is practical for heparin monitoring
      during postoperative and long-term care. This study thus demonstrates a new
      synthetic strategy to develop GO-based chemical and biological sensing without
      the employment of dye-labeled biomolecules.

PMID- 21882809
TI  - Quantum chemistry behind bioimaging: insights from ab initio studies of
      fluorescent proteins and their chromophores.
AB  - The unique properties of green fluorescent protein (GFP) have been harnessed in a
      variety of bioimaging techniques, revolutionizing many areas of the life
      sciences. Molecular-level understanding of the underlying photophysics provides
      an advantage in the design of new fluorescent proteins (FPs) with improved
      properties; however, because of its complexity, many aspects of the GFP
      photocycle remain unknown. In this Account, we discuss computational studies of
      FPs and their chromophores that provide qualitative insights into mechanistic
      details of their photocycle and the structural basis for their optical
      properties. In a reductionist framework, studies of well-defined model systems
      (such as isolated chromophores) help to understand their intrinsic properties,
      while calculations including protein matrix and/or solvent demonstrate, on the
      atomic level, how these properties are modulated by the environment. An
      interesting feature of several anionic FP chromophores in the gas phase is their
      low electron detachment energy. For example, the bright excited pipi* state of
      the model GFP chromophore (2.6 eV) lies above the electron detachment continuum
      (2.5 eV). Thus, the excited state is metastable with respect to electron
      detachment. This autoionizing character needs to be taken into account in
      interpreting gas-phase measurements and is very difficult to describe
      computationally. Solvation (and even microsolvation by a single water molecule)
      stabilizes the anionic states enough such that the resonance excited state
      becomes bound. However, even in stabilizing environments (such as protein or
      solution), the anionic chromophores have relatively low oxidation potentials and
      can act as light-induced electron donors. Protein appears to affect excitation
      energies very little (<0.1 eV), but alters ionization or electron detachment
      energies by several electron volts. Solvents (especially polar ones) have a
      pronounced effect on the chromophore's electronic states; for example, the
      absorption wavelength changes considerably, the ground-state barrier for cis
      trans isomerization is reduced, and fluorescence quantum yield drops
      dramatically. Calculations reveal that these effects can be explained in terms of
      electrostatic interactions and polarization, as well as specific interactions
      such as hydrogen bonding. The availability of efficient computer implementations
      of predictive electronic structure methods is essential. Important challenges
      include developing faster codes (to enable better equilibrium sampling and
      excited-state dynamics modeling), creating algorithms for properties calculations
      (such as nonlinear optical properties), extending standard excited-state methods
      to autoionizing (resonance) states, and developing accurate QM/MM schemes. The
      results of sophisticated first-principle calculations can be interpreted in terms
      of simpler, qualitative molecular orbital models to explain general trends. In
      particular, an essential feature of the anionic GFP chromophore is an almost
      perfect resonance (mesomeric) interaction between two Lewis structures, giving
      rise to charge delocalization, bond-order scrambling, and, most importantly,
      allylic frontier molecular orbitals spanning the methine bridge. We demonstrate
      that a three-center Huckel-like model provides a useful framework for
      understanding properties of FPs. It can explain changes in absorption wavelength
      upon protonation or other structural modifications of the chromophore, the
      magnitude of transition dipole moment, barriers to isomerization, and even non
      Condon effects in one- and two-photon absorption.

PMID- 21882810
TI  - Group 14 hydrides with low valent elements for activation of small molecules.
AB  - Transition metal compounds are well known as activators of small molecules, and
      they serve as efficient catalysts for a variety of homogeneous and heterogeneous
      transformations. In contrast, there is a general feeling that main group
      compounds cannot act as efficient catalysts because of their inability to
      activate small molecules. Traditionally, the activation of small molecules is
      considered one of the key steps during a catalytic cycle with transition metals.
      As a consequence, researchers have long neglected the full range of possibilities
      in harnessing main group elements for the design of efficient catalysts.  Recent
      developments, however, have made it possible to synthesize main group compounds
      with low-valent elements capable of activating small molecules. In particular,
      the judicious use of sterically appropriate ligands has been successful in
      preparing and stabilizing a variety of Group 14 hydrides with low-valent
      elements. In this Account, we discuss recent advances in the synthesis of Group
      14 hydrides with low-valent elements and assess their potential as small-molecule
      activators.  Group 14, which comprises the nonmetal C, the semimetals Si and Ge,
      and the metals Sn and Pb, was for years a source of hydrides with the Group 14
      element almost exclusively in tetravalent form. Synthetic difficulties and the
      low stability of Group 14 hydrides in lower oxidation states were difficult to
      overcome. But in 2000, a divalent Sn(II) hydride was prepared as a stable
      compound through the incorporation of sterically encumbered aromatic ligands.
      More recently, the stabilization of GeH(2) and SnH(2) complexes using an N
      heterocyclic carbene (NHC) as a donor and BH(3) or a metal carbonyl complex as an
      acceptor was reported. A similar strategy was also employed to synthesize the
      Si(II) hydride. This class of hydrides may be considered coordinatively
      saturated, with the lone pair of electrons on the Group 14 elements taking part
      in coordination.  We discuss the large-scale synthesis of hydrides of the form
      LMH (where M is Ge or Sn, L is CH(N(Ar)(CMe))(2), and Ar is 2,6-iPr(2)C(6)H(3)),
      which has made it possible to test their reactivity in the activation of small
      molecules. Unlike the tetravalent Group 14 hydrides, the Ge(II) and Sn(II)
      hydrides were found to be able to activate a number of small molecules in the
      absence of any externally added catalyst. For example, the Ge(II) hydride and
      Sn(II) hydride can activate CO(2), and the reaction results in the formation of
      Ge(II) and Sn(II) esters of formic acid. This product represents a prototype of a
      new class of compounds of Group 14 elements. Moreover, we examined the activation
      of carbonyl compounds, alkynes, diazo and azo compounds, azides, and compounds
      containing the C?N bond. These Group 14 hydrides with low-valent elements are
      shown to be able to activate a number of important small molecules with C=C, C?O,
      N?N, and C?N bonds.  The activation of small molecules is an important step
      forward in the realization of main group catalyst development. Although it is not
      yet customary to assay the potential of newly synthesized main group compounds
      for small-molecule activation, our results offer good reason to do so.

PMID- 21882811
TI  - Trafficking of platelet-activating factor acetylhydrolase type II in response to
      oxidative stress.
AB  - Platelet-activating factor acetylhydrolase type II (PAFAH-II) is an intracellular
      phospholipase A(2) enzyme that hydrolyzes platelet-activating factor and
      oxidatively fragmented phospholipids. This N-terminally myristoylated protein
      becomes associated with cytoplasm-facing cell membranes under oxidative stress.
      The structural requirements for binding of PAFAH-II to membranes in response to
      oxidative stress are unknown. To begin elucidating the mechanism of trafficking
      and stress response, we constructed a homology model of PAFAH-II. From the
      predicted membrane orientation of PAFAH-II, the N-terminal myristoyl group and a
      hydrophobic patch are hypothesized to be involved in membrane binding.
      Localization studies of human PAFAH-II in HEK293 cells indicated that an
      unmyristoylated mutant remained cytoplasmic under stressed and unstressed
      conditions. The myristoylated wild-type enzyme was partially localized to the
      cytoplasmic membranes prior to stress and became more localized to these
      membranes upon stress. A triple mutation of three hydrophobic patch residues of
      the membrane binding region likewise did not localize to membranes following
      stress. These results indicate that both the myristoyl group and the hydrophobic
      patch are essential for proper trafficking of the enzyme to the membranes
      following oxidative stress. Additionally, colocalization studies using organelle
      specific proteins demonstrate that PAFAH-II is transported to the membranes of
      both the endoplasmic reticulum and Golgi apparatus.

PMID- 21882812
TI  - Regioselective copper-mediated synthesis of thieno[2,3-c]pyrane-7-one, indolo[2,3
      c]pyrane-1-one, and indolo[3,2-c]pyrane-1-one.
AB  - In the presence of copper(I) iodide, heteroaromatic beta-iodo-alpha,beta
      unsaturated carboxylic acid systems opposed to terminal alkyne afford selectively
      6-endo-dig cyclization products via a tandem coupling oxacyclization reaction.

PMID- 21882814
TI  - A practical, one-pot synthesis of highly substituted thiophenes and
      benzo[b]thiophenes from bromoenynes and o-alkynylbromobenzenes.
AB  - An efficient synthesis of thiophenes and benzo[b]thiophenes has been developed
      from easily available bromoenynes and o-alkynylbromobenzene derivatives. This
      novel one-pot procedure involves a Pd-catalyzed C-S bond formation using a
      hydrogen sulfide surrogate followed by a heterocyclization reaction. Moreover, in
      situ functionalization with selected electrophiles further expands the potential
      of this methodology to the preparation of the corresponding highly substituted
      sulfur heterocycles.

PMID- 21882816
TI  - Therapeutic and cytotoxic effects of the novel antipsoriasis codrug, naproxyl
      dithranol, on HaCaT cells.
AB  - A novel topical codrug, naproxyl-dithranol (Nap-DTH), in which dithranol and
      naproxen are linked via an ester in a 1:1 ratio to form a single chemical entity,
      was synthesized. The antiproliferative, anti-inflammatory and toxic effects of
      Nap-DTH were assessed, at the cellular level, using various in vitro methods.
      Cultured HaCaT keratinocytes were treated with Nap-DTH, and the cellular effects
      were compared with those of the parent compounds, individually and as a 1:1
      mixture of naproxen:dithranol to mimic 1:1 in situ liberation from Nap-DTH. The
      results demonstrate that Nap-DTH did not modify proliferation and only exhibited
      slight toxic effects after 24 h at concentrations >21 MUM. At a lower
      concentration (3.4 MUM), Nap-DTH did not alter cell proliferation or
      inflammation, which suggests that the codrug is therapeutically inert. Relating
      to this, the 1:1 mixture of naproxen:dithranol exhibited the lowest toxic effect
      and the highest antiproliferative effect on HaCaT keratinocytes compared to
      dithranol at the same concentration. Moreover, the 1:1 mixture exhibited a
      reduced inflammatory effect compared to dithranol alone, as reflected by the
      upregulation of cyclooxygenase-2 by 45% and 136%, respectively. In spite of the
      1:1 mixture showing a greater downregulation of Ki-67 and a 2-fold reduction of
      proliferating cell nuclear antigen (both cellular markers of proliferation) than
      dithranol, dithranol showed a much greater induction of cleaved caspase-3 protein
      expression (upregulated by 287%, compared to 85% for the 1:1 mixture). This
      suggests that when dithranol was administered with naproxen, inhibition of cell
      growth plays a more important role in the antiproliferation effects than the
      induction of apoptotic cell death. These results confirm that the codrug would
      lead to a better therapeutic profile and fewer adverse effects compared to its
      parent compounds.

PMID- 21882817
TI  - Gas phase synthesis of Au clusters deposited on titanium oxide clusters and their
      reactivity with CO molecules.
AB  - Titanium oxide clusters were formed in the gas phase by the laser ablation of a
      Ti rod in the presence of oxygen in a He gas. Not only stoichiometric but also
      nonstoichiometric titanium oxide clusters, Ti(n)O(2n+x)(+) (n = 1-22 and x = -1
      3), were formed. The content of oxygen atoms depends strongly on a partial
      pressure of oxygen. Gold clusters, Au(m) (m = 1-4), were generated by the laser
      ablation, which were then deposited on Ti(n)O(2n+x) clusters. The formation of
      Au(m)Ti(n)O(2n+x)(+) follows electron transfer from Au(m) to Ti(n)O(2n+x)(+). The
      reactivity of Au(m)Ti(n)O(2n+x)(+) cluster ions with CO was examined for
      different m, n, and x by the mass spectrometry. It was found that Au(m) on
      Ti(n)O(2n-1)(+) are less reactive than those on the other Ti(n)O(2n+x)(+) (x = 0
      and 1). In addition, the reactivity is highest when Au(m) (m = 1 and 3) is on the
      stoichiometric titanium oxide (x = 0), whereas the reactivity is also high when
      Au(2) is on the oxygen-rich titanium oxide (x = 1). The reactivity was found to
      relate to geometrical structures of Au(m)Ti(n)O(2n+x)(+), which were studied by
      density functional calculations.

PMID- 21882818
TI  - A compound that inhibits the HOP-Hsp90 complex formation and has unique killing
      effects in breast cancer cell lines.
AB  - The chaperone Hsp90 is required for the correct folding and maturation of certain
      "client proteins" within all cells. Hsp90-mediated folding is particularly
      important in cancer cells, because upregulated or mutant oncogenic proteins are
      often Hsp90 clients. Hsp90 inhibitors thus represent a route to anticancer agents
      that have the potential to be active against several different types of cancer.
      Currently, various Hsp90 inhibitors that bind to Hsp90 at its ATP-binding site
      are in preclinical and clinical trials. Some of the most promising Hsp90 ATP
      binding site inhibitors are the well characterized geldanamycin derivative 17-AAG
      and the recently described compounds PU-H71 and NVP-AUY922. An undesirable
      characteristic of these compounds is the transcriptional upregulation of Hsp70
      that has prosurvival effects. Here we characterize the activity of a new type of
      chaperone inhibitor, 1,6-dimethyl-3-propylpyrimido[5,4-e][1,2,4]triazine-5,7
      dione (named C9 for simplicity). Using purified protein components in vitro, C9
      prevents Hsp90 from interacting with the cochaperone HOP and is thus expected to
      impair the Hsp90-dependent folding pathway in vivo. We show that this compound is
      effective in killing various breast cancer cell lines including the highly
      metastatic MDA-MB-231. An important property of this compound is that it does not
      induce the transcriptional upregulation of Hsp70. Moreover, when cells are
      treated with a combination of C9 and either 17-AAG or NVP-AUY922, the
      overexpression of Hsp70 is counteracted considerably and C9's lethal-IC50
      decreases compared to its value when added alone.

PMID- 21882819
TI  - Plasmonic green nanolaser based on a metal-oxide-semiconductor structure.
AB  - Realization of smaller and faster coherent light sources is critically important
      for the emerging applications in nanophotonics and information technology.
      Semiconductor lasers are arguably the most suitable candidate for such purposes.
      However, the minimum size of conventional semiconductor lasers utilizing
      dielectric optical cavities for sustaining laser oscillation is ultimately
      governed by the diffraction limit (~(lambda/2n)(3) for three-dimensional (3D)
      cavities, where lambda is the free-space wavelength and n is the refractive
      index). Here, we demonstrate the 3D subdiffraction-limited laser operation in the
      green spectral region based on a metal-oxide-semiconductor (MOS) structure,
      comprising a bundle of green-emitting InGaN/GaN nanorods strongly coupled to a
      gold plate through a SiO(2) dielectric nanogap layer. In this plasmonic
      nanocavity structure, the analogue of MOS-type "nanocapacitor" in nanoelectronics
      leads to the confinement of the plasmonic field into a 3D mode volume of 8.0 *
      10(-4) MUm(3) (~0.14(lambda/2n)(3)).

PMID- 21882820
TI  - Small molecule receptor protein tyrosine phosphatase gamma (RPTPgamma) ligands
      that inhibit phosphatase activity via perturbation of the tryptophan-proline
      aspartate (WPD) loop.
AB  - Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of tyrosine
      residues, a process that involves a conserved tryptophan-proline-aspartate (WPD)
      loop in catalysis. In previously determined structures of PTPs, the WPD-loop has
      been observed in either an "open" conformation or a "closed" conformation. In the
      current work, X-ray structures of the catalytic domain of receptor-like protein
      tyrosine phosphatase gamma (RPTPgamma) revealed a ligand-induced "superopen"
      conformation not previously reported for PTPs. In the superopen conformation, the
      ligand acts as an apparent competitive inhibitor and binds in a small hydrophobic
      pocket adjacent to, but distinct from, the active site. In the open and closed
      WPD-loop conformations of RPTPgamma, the side chain of Trp1026 partially occupies
      this pocket. In the superopen conformation, Trp1026 is displaced allowing a 3,4
      dichlorobenzyl substituent to occupy this site. The bound ligand prevents closure
      of the WPD-loop over the active site and disrupts the catalytic cycle of the
      enzyme.

PMID- 21882821
TI  - Neptunium thiophosphate chemistry: intermediate behavior between uranium and
      plutonium.
AB  - Black crystals of Np(PS(4)), Np(P(2)S(6))(2), K(11)Np(7)(PS(4))(13), and
      Rb(11)Np(7)(PS(4))(13) have been synthesized by the reactions of Np, P(2)S(5),
      and S at 1173 and 973 K; Np, K(2)S, P, and S at 773 K; and Np, Rb(2)S(3), P, and
      S at 823 K, respectively. The structures of these compounds have been
      characterized by single-crystal X-ray diffraction methods. Np(PS(4)) adopts a
      three-dimensional structure with Np atoms coordinated to eight S atoms from four
      bidentate PS(4)(3-) ligands in a distorted square antiprismatic arrangement.
      Np(PS(4)) is isostructural to Ln(PS(4)) (Ln = La-Nd, Sm, Gd-Er). The structure of
      Np(P(2)S(6))(2) is constructed from three interpenetrating diamond-type
      frameworks with Np atoms coordinated to eight S atoms from four bidentate
      P(2)S(6)(2-) ligands in a distorted square antiprismatic geometry. The
      centrosymmetric P(2)S(6)(2-) anion comprises two PS(2) groups connected by two
      bridging S centers. Np(P(2)S(6))(2) is isostructural to U(P(2)S(6))(2).
      A(11)Np(7)(PS(4))(13) (A = K, Rb) adopts a three-dimensional channel structure
      built from interlocking [Np(7)(PS(4))(13)](11-)-screw helices with A cations
      residing in the channels. The structure of A(11)Np(7)(PS(4))(13) includes four
      crystallographically independent Np atoms. Three are connected to eight S atoms
      in bicapped trigonal prisms. The other Np atom is connected to nine S atoms in a
      tricapped trigonal prism. A(11)Np(7)(PS(4))(13) is isostructural to
      A(11)U(7)(PS(4))(13). From Np-S bond distances and charge-balance, we infer that
      Np is trivalent in Np(PS(4)) and tetravalent in Np(P(2)S(6))(2) and
      A(11)Np(7)(PS(4))(13). Np exhibits a behavior intermediate between U and Pu in
      its thiophosphate chemistry.

PMID- 21882822
TI  - Theoretical investigation for the cycle reaction of N2O (x1?+) with CO (1?+)
      catalyzed by IrO(n)+ (n = 1, 2) and utilizing the energy span model to study its
      kinetic information.
AB  - The mechanisms of the reactions between N(2)O and CO catalyzed by IrO(n)(+) (n =
      1, 2) have been investigated using B3LYP and CCSD(T) levels of theory. Spin
      inversion among three reaction profiles corresponding to the quintet, triplet,
      and singlet multiplicities was discussed by using spin-orbit coupling (SOC)
      calculations. The probability of electron hopping in the vicinity of the (MECP)
      has been calculated by the Landau-Zener-type model. The single P(1)(ISC) and
      double P(2)(ISC) passes estimated at MECP1(#) (SOC = 198.61 cm(-1)) are
      approximately 0.11 and 0.20, respectively. Important analysis and explanations
      were done using molecular orbital theory and natural bonding orbital (NBO). The
      energetic span (deltaE) model coined by Kozuch was applied in this cycle. The
      turnover frequency (TOF)-determining transition state (TDTS) and TDI (TOF
      determining intermediate) were confirmed. Finally, TOF(IrO(+))/TOF(IrO(2)(+)) =
      0.38 at 298 K.

PMID- 21882823
TI  - Preparation of cystamine core dendrimer and antibody-dendrimer conjugates for MRI
      angiography.
AB  - Herein we report the preparation along with the in vivo and in vitro MRI
      characterization of two generation four and five cystamine core dendrimers loaded
      with thirty and fifty-eight derivatized Gd-DOTA (G4SS30, G5SS58) respectively.
      Likewise the development and characterization of two half-dendrimers conjugated
      to the F(ab')(2) fragment of the monoclonal antibody (mAb) panitumumab
      functionalized with a maleimide conjugation functional group site (Ab-(G4S15)(4),
      Ab-(G5S29)(4)) are also described. The in vitro molar relaxivity of the Ab
      (G4S15)(4) conjugate, measured at pH 7.4, 22  degrees C, and 3T showed a moderate
      increase in relaxivity as compared to Magnevist (6.7 vs 4.0 mM(-1) s(-1)) while
      the Ab-(G5S29)(4) conjugate was 2-fold higher (9.1 vs 4.0 mM(-1) s(-1)). The data
      showed that only a high injection dose (0.050 mmol Gd(3+)/kg) produced a
      detectable contrast enhanced contrast for the Ab-(G4S15)(4) conjugate while a
      lower dose (0.035 mmol Gd(3+)/kg) was sufficient for the Ab-(G5S29)(4) conjugate.
      The antibody-SMCC conjugate was purified by a Sephadex G-100 column, and the
      antibody-dendrimer-based agents were purified by spin filtration using a
      Centricon filter (50,000 MCO). The protein assay coupled with cysteine and
      Ellman's assay indicated an antibody to dendrimer ratio of 1:4. The in vivo blood
      clearance half-lives of the four agents measured at the jugular vein were ~12-22
      min.

PMID- 21882824
TI  - Ar solvation shells in K(+)-HFBz: from cluster rearrangement to solvation
      dynamics.
AB  - The effect of some leading intermolecular interaction components on specific
      features of weakly bound clusters involving an aromatic molecule, a closed shell
      ion, and Ar atoms is analyzed by performing molecular dynamics simulations on
      potential energy surfaces properly formulated in a consistent way. In particular,
      our investigation focuses on the three-dimensional Ar distributions around the
      K(+)-hexafluorobenzene (K(+)-HFBz) dimer, in K(+)-HFBz-Ar(n) aggregates (n <=
      15), and on the gradual evolution from cluster rearrangement to solvation
      dynamics when ensembles of 50, 100, 200, and 500 Ar atoms are taken into account.
      Results indicate that the Ar atoms compete to be placed in such a way to favor an
      attractive interaction with both K(+) and HFBz, occupying positions above and
      below the aromatic plane but close to the cation. When these positions are
      already occupied, the Ar atoms tend to be placed behind the cation, at larger
      distances from the center of mass of HFBz. Accordingly, three different groups of
      Ar atoms are observed when increasing n, with two of them surrounding K(+), thus,
      disrupting the K(+)-HFBz equilibrium geometry and favoring the dissociation of
      the solvated cation when the temperature increases. The selective role of the
      leading intermolecular interaction components directly depending on the ion size
      repulsion is discussed in detail by analyzing similarities and differences on the
      behavior of the Ar-solvated K(+)-HFBz and Cl(-)-Bz aggregates.

PMID- 21882825
TI  - Mannose-functionalized "pathogen-like" polyanhydride nanoparticles target C-type
      lectin receptors on dendritic cells.
AB  - Targeting pathogen recognition receptors on dendritic cells (DCs) offers the
      advantage of triggering specific signaling pathways to induce a tailored and
      robust immune response. In this work, we describe a novel approach to targeted
      antigen delivery by decorating the surface of polyanhydride nanoparticles with
      specific carbohydrates to provide "pathogen-like" properties that ensure
      nanoparticles engage C-type lectin receptors on DCs. The surface of polyanhydride
      nanoparticles was functionalized by covalent linkage of dimannose and lactose
      residues using an amine-carboxylic acid coupling reaction. Coculture of
      functionalized nanoparticles with bone marrow-derived DCs significantly increased
      cell surface expression of MHC II, the T cell costimulatory molecules CD86 and
      CD40, the C-type lectin receptor CIRE and the mannose receptor CD206 over the
      nonfunctionalized nanoparticles. Both nonfunctionalized and functionalized
      nanoparticles were efficiently internalized by DCs, indicating that
      internalization of functionalized nanoparticles was necessary but not sufficient
      to activate DCs. Blocking the mannose and CIRE receptors prior to the addition of
      functionalized nanoparticles to the culture inhibited the increased surface
      expression of MHC II, CD40 and CD86. Together, these data indicate that
      engagement of CIRE and the mannose receptor is a key mechanism by which
      functionalized nanoparticles activate DCs. These studies provide valuable
      insights into the rational design of targeted nanovaccine platforms to induce
      robust immune responses and improve vaccine efficacy.

PMID- 21882826
TI  - Functional regulation of an immobilized redox protein on an oriented metal
      coordinated peptide monolayer as an electron mediator.
AB  - We fabricated a vertically and unidirectionally oriented metal coordinated alpha
      helical peptide monolayer, Leu(2)Ala(Pyri)(Co(II))Leu(6)Ala(4
      Pyri)(Co(II))Leu(6), by stepwise polymerization on a mixed self-assembled
      monolayer consisting of amino-alkanethiol, dialkyl disulfide, and ferrocenyl
      alkanethiol acted as a photoresponsive electron donor. Redox-active protein,
      nitrate reductase (NR), was fixed on the surface of the peptide monolayer. By
      contrast, we fixed NR on the mixed self-assembled monolayer directly. Upon
      photoirradiation, electron flow occurred from the excited ferrocenyl group on the
      substrate to the electron acceptor, NR, on the surface of the molecular layers.
      The activated NR on the molecular layers reduced the nitrate to nitrite. The
      amount of the bioelectrocatalytic product, nitrite, generated by the immobilized
      NR on the peptide monolayer was larger than that produced by the immobilized NR
      on the mixed self-assembled monolayer directly. That is to say, the NR on the
      peptide monolayer has been more activated rather than that on the peptide absent
      monolayer by photoirradiation. The effective activation of the NR on the peptide
      monolayer can be explained in terms of enhancement of the vectorial electron flow
      along the macro-dipole moment of the alpha-helical peptide that arranged
      unidirectionally. It suggested that the ordered metal coordinated alpha-helical
      peptide monolayer acted as an efficient electron mediator to achieve a
      communication between the electron donor and the redox-active moiety. Such a
      hybrid molecular system looks promising for novel nanodevices, such as nano
      photoreactors.

PMID- 21882828
TI  - Supramolecular polymers in aqueous medium: rational design based on directional
      hydrophobic interactions.
AB  - Self-assembly in aqueous medium is of primary importance and widely employs
      hydrophobic interactions. Yet, unlike directional hydrogen bonds, hydrophobic
      interactions lack directionality, making difficult rational self-assembly design.
      Directional hydrophobic motif would significantly enhance rational design in
      aqueous self-assembly, yet general approaches to such interactions are currently
      lacking. Here, we show that pairwise directional hydrophobic/pi-stacking
      interactions can be designed using well-defined sterics and supramolecular
      multivalency. Our system utilizes a hexasubstituted benzene scaffold decorated
      with 3 (compound 1) or 6 (compound 2) amphiphilc perylene diimides. It imposes a
      pairwise self-assembly mode, leading to well-defined supramolecular polymers in
      aqueous medium. the assemblies were characterized using cryogenic electron
      microscopy, small-angle X-ray scattering, optical spectroscopy, and EPR.
      Supramolecular polymerization studies in the case of 2 revealed association
      constants in 10(8) M(-1) range, and significant enthalpic contribution to the
      polymerization free energy. The pairwise PDI motif enables exciton confinement
      and localized emission in the polymers based on 1 and 2's unique photonic
      behavior, untypical of the extended pi-stacked systems. Directional pairwise
      hydrophobic interactions introduce a novel strategy for rational design of
      noncovalent assemblies in aqueous medium, and bring about a unique photofunction.

PMID- 21882829
TI  - Total synthesis of echinopines A and B: exploiting a bioinspired late-stage
      intramolecular cyclopropanation.
AB  - Total synthesis of echinopine A and B have been accomplished, based on a strategy
      that involved two transition-metal-mediated ene-yne cycloisomerizations. A
      modified Pd-catalyzed enyne cycloisomerization/intramolecular Diels-Alder cascade
      rendered a more streamlined synthesis of tricyclic ketone 15, and a Ru-catalyzed
      ene-yne cycloisomerization/cyclopropanation resembled the late-stage [5/7] ->
      [3/5/5/7] ring-forming sequence in the proposed biosynthetic pathway.

PMID- 21882827
TI  - The development of N-alpha-(2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-l
      ornithine amide (o-F-amidine) and N-alpha-(2-carboxyl)benzoyl-N(5)-(2-chloro-1
      iminoethyl)-l-ornithine amide (o-Cl-amidine) as second generation protein
      arginine deiminase (PAD) inhibitors.
AB  - Protein arginine deiminase (PAD) activity is upregulated in a number of human
      diseases, including rheumatoid arthritis, ulcerative colitis, and cancer. These
      enzymes, there are five in humans (PADs 1-4 and 6), regulate gene transcription,
      cellular differentiation, and the innate immune response. Building on our
      successful generation of F- and Cl-amidine, which irreversibly inhibit all of the
      PADs, a structure-activity relationship was performed to develop second
      generation compounds with improved potency and selectivity. Incorporation of a
      carboxylate ortho to the backbone amide resulted in the identification of N-alpha
      (2-carboxyl)benzoyl-N(5)-(2-fluoro-1-iminoethyl)-l-ornithine amide (o-F-amidine)
      and N-alpha-(2-carboxyl)benzoyl-N(5)-(2-chloro-1-iminoethyl)-l-ornithine amide (o
      Cl-amidine), as PAD inactivators with improved potency (up to 65-fold) and
      selectivity (up to 25-fold). Relative to F- and Cl-amidine, the compounds also
      show enhanced potency in cellulo. As such, these compounds will be versatile
      chemical probes of PAD function.

PMID- 21882830
TI  - From HCOOH to CO at Pd electrodes: a surface-enhanced infrared spectroscopy
      study.
AB  - The decomposition of HCOOH on Pd surfaces over a potential range of practical
      relevance to hydrogen production and fuel cell anode operation was probed by
      combining high-sensitivity in situ surface-enhanced IR spectroscopy with
      attenuated total reflection and thin-layer flow cell configurations. For the
      first time, concrete spectral evidence of CO(ad) formation has been obtained, and
      a new main pathway from HCOOH to CO(ad) involving the reduction of the
      dehydrogenation product of HCOOH (i.e., CO(2)) is proposed.

PMID- 21882832
TI  - Synthesis and biological evaluation of novel analogues of the pan class I
      phosphatidylinositol 3-kinase (PI3K) inhibitor 2-(difluoromethyl)-1-[4,6-di(4
      morpholinyl)-1,3,5-triazin-2-yl]-1H-benzimidazole (ZSTK474).
AB  - A structure-activity relationship (SAR) study of the pan class I PI 3-kinase
      inhibitor 2-(difluoromethyl)-1-[4,6-di(4-morpholinyl)-1,3,5-triazin-2-yl]-1H
      benzimidazole (ZSTK474) identified substitution at the 4 and 6 positions of the
      benzimidazole ring as having significant effects on the potency of substituted
      derivatives. The 6-amino-4-methoxy analogue displayed a greater than 1000-fold
      potency enhancement over the corresponding 6-aza-4-methoxy analogue against all
      three class Ia PI 3-kinase enzymes (p110alpha, p110beta, and p110delta) and also
      displayed significant potency against two mutant forms of the p110alpha isoform
      (H1047R and E545K). This compound was also evaluated in vivo against a U87MG
      human glioblastoma tumor xenograft model in Rag1(-/-) mice, and at a dose of 50
      mg/kg given by ip injection at a qd * 10 dosing schedule it dramatically reduced
      cancer growth by 81% compared to untreated controls.

PMID- 21882833
TI  - Silica shell/gold core nanoparticles: correlating shell thickness with the
      plasmonic red shift upon aggregation.
AB  - Differences in the wavelengths of the surface plasmon band of gold nanoparticles
      (AuNP)--before and after particle aggregation--are widely used in bioanalytical
      assays. However, the gold surfaces in such bioassays can suffer from exchange and
      desorption of noncovalently bound ligands and from nonspecific adsorption of
      biomolecules. Silica shells on the surfaces of the gold can extend the available
      surface chemistries for bioconjugation and potentially avoid these issues.
      Therefore, silica was grown on gold surfaces using either hydrolysis/condensation
      of tetraethyl orthosilicate 1 under basic conditions or diglyceroxysilane 2 at
      neutral pH. The former precursor permitted slow, controlled growth of shells from
      about 1.7 to 4.3 nm thickness. By contrast, 3-4 nm thick silica shells formed
      within an hour using diglyceroxysilane; thinner or thicker shells were not
      readily available. Within the range of shell thicknesses synthesized, the
      presence of a silica shell on the gold nanoparticle did not significantly affect
      the absorbance maximum (~5 nm) of unaggregated particles. However, the change in
      absorbance wavelength upon aggregation of the particles was highly dependent on
      the thickness of the shell. With silica shells coating the AuNP, there was a
      significant decrease in the absorbance maximum of the aggregated particles, from
      ~578 to ~536 nm, as the shell thicknesses increased from ~1.7 to ~4.3 nm, because
      of increased distance between adjacent gold cores. These studies provide guidance
      for the development of colorimetric assays using silica-coated AuNP.

PMID- 21882831
TI  - Discovery of novel alkylated (bis)urea and (bis)thiourea polyamine analogues with
      potent antimalarial activities.
AB  - A series of alkylated (bis)urea and (bis)thiourea polyamine analogues were
      synthesized and screened for antimalarial activity against chloroquine-sensitive
      and -resistant strains of  Plasmodium falciparum  in vitro. All analogues showed
      growth inhibitory activity against P. falciparum at less than 3 MUM, with the
      majority having effective IC(50) values in the 100-650 nM range. Analogues
      arrested parasitic growth within 24 h of exposure due to a block in nuclear
      division and therefore asexual development. Moreover, this effect appears to be
      cytotoxic and highly selective to malaria parasites (>7000-fold lower IC(50)
      against P. falciparum) and is not reversible by the exogenous addition of
      polyamines. With this first report of potent antimalarial activity of polyamine
      analogues containing 3-7-3 or 3-6-3 carbon backbones and substituted terminal
      urea- or thiourea moieties, we propose that these compounds represent a
      structurally novel class of antimalarial agents.

PMID- 21882834
TI  - Shape and eccentricity effects in adhesive contacts of rodlike particles.
AB  - The effects of shape and eccentricity on adhesion and detachment behavior of
      long, rodlike particles in contact with a half-space are analyzed using contact
      mechanics. The particles are considered to have cross sections that are squarish,
      oblate, or prolate rather than circular. Such cross sections are represented very
      generally by using superellipses. The contact mechanics model allows deduction of
      closed-form expressions for the contact pressure, load-contact size relation,
      detachment load, and detachment contact size. It is found that even relatively
      small deviations in shape from a cylinder have a significant influence on the
      detachment load. Eccentricity also affects the adhesive behavior, but to a lesser
      extent, with oblate shapes requiring larger separation loads than prolate shapes.
      The load-contact size solution reduces to that for a right-circular, cylindrical
      rod when the appropriate limit is taken. The detachment behavior of right
      circular cylinders is also found to be mimicked by an entire family of rod shapes
      with different cross sections.

PMID- 21882835
TI  - Fractionation of stable zinc isotopes in the zinc hyperaccumulator Arabidopsis
      halleri and nonaccumulator Arabidopsis petraea.
AB  - Zn isotope fractionation may provide new insights into Zn uptake, transport and
      storage mechanisms in plants. It was investigated here in the Zn hyperaccumulator
      Arabidopsis halleri and the nonaccumulator A. petraea. Plant growth on hydroponic
      solution allowed us to measure the isotope fractionation between source Zn (with
      Zn(2+) as dominant form), shoot and root. Zn isotope mass balance yields mean
      isotope fractionation between plant and source Zn Delta(66)Zn(in-source) of -0.19
      +/- 0.200/00 in the nonaccumulator and of -0.05 +/- 0.120/00 in the
      hyperaccumulator. The isotope fractionation between shoot Zn and bulk Zn
      incorporated (Delta(66)Zn(shoot-in)) differs between the nonaccumulator and the
      hyperaccumulator and is function of root-shoot translocation (as given by mass
      ratio between shoot Zn and bulk plant Zn). The large isotope fractionation
      associated with sequestration in the root (0.370/00) points to the binding of
      Zn(2+) with a high affinity ligand in the root cell. We conclude that Zn stable
      isotopes may help to estimate underground and aerial Zn storage in plants and be
      useful in studying extracellular and cellular mechanisms of sequestration in the
      root.

PMID- 21882836
TI  - Optimizing sensitization processes in dinuclear luminescent lanthanide oligomers:
      selection of rigid aromatic spacers.
AB  - This work illustrates a simple approach for optimizing the lanthanide
      luminescence in molecular dinuclear lanthanide complexes and identifies a
      particular multidentate europium complex as the best candidate for further
      incorporation into polymeric materials. The central phenyl ring in the bis
      tridentate model ligands L3-L5, which are substituted with neutral (X = H, L3),
      electron-withdrawing (X = F, L4), or electron-donating (X = OCH3, L5) groups,
      separates the 2,6-bis(benzimidazol-2-yl)pyridine binding units of linear
      oligomeric multi-tridentate ligand strands that are designed for the complexation
      of luminescent trivalent lanthanides, Ln(III). Reactions of L3-L5 with
      [Ln(hfac)3(diglyme)] (hfac- is the hexafluoroacetylacetonate anion) produce
      saturated single-stranded dumbbell-shaped complexes [Ln2(Lk)(hfac)6] (k = 3-5),
      in which the lanthanide ions of the two nine-coordinate neutral [N3Ln(hfac)3]
      units are separated by 12-14 A. The thermodynamic affinities of [Ln(hfac)3] for
      the tridentate binding sites in L3-L5 are average (6.6 <= log(beta(2,1)(Y,Lk)) <=
      8.4) but still result in 15-30% dissociation at millimolar concentrations in
      acetonitrile. In addition to the empirical solubility trend found in organic
      solvents (L4 > L3 >> L5), which suggests that the 1,4-difluorophenyl spacer in L4
      is preferable, we have developed a novel tool for deciphering the photophysical
      sensitization processes operating in [Eu2(Lk)(hfac)6]. A simple interpretation of
      the complete set of rate constants characterizing the energy migration mechanisms
      provides straightforward objective criteria for the selection of [Eu2(L4)(hfac)6]
      as the most promising building block.

PMID- 21882837
TI  - Evaluation of HPbetaCD-PEG microparticles for salmon calcitonin administration
      via pulmonary delivery.
AB  - For therapeutic peptides, the lung represents an attractive, noninvasive route
      into the bloodstream. To achieve optimal bioavailability and control their fast
      rate of absorption, peptides can be protected by coprocessing with polymers such
      as polyethylene glycol (PEG). Here, we formulated and characterized salmon
      calcitonin (sCT)-loaded microparticles using linear or branched PEG (L-PEG or B
      PEG) and hydroxypropyl-beta-cyclodextrin (HPbetaCD) for pulmonary administration.
      Mixtures of sCT, L-PEG or B-PEG and HPbetaCD were co-spray dried. Based on the
      particle properties, the best PEG:HPbetaCD ratio was 1:1 w:w for both PEGs. In
      the sCT-loaded particles, the L-PEG was more crystalline than B-PEG. Thus, L-PEG
      based particles had lower surface free energy and better aerodynamic behavior
      than B-PEG-based particles. However, B-PEG-based particles provided better
      protection against chemical degradation of sCT. A decrease in sCT permeability,
      measured across Calu-3 bronchial epithelial monolayers, occurred when the PEG and
      HPbetaCD concentrations were both 1.6 wt %. This was attributed to an increase in
      buffer viscosity, caused by the two excipients. sCT pharmacokinetic profiles in
      Wistar rats were evaluated using a 2-compartment model after iv injection or lung
      insufflation. The maximal sCT plasma concentration was reached within 3 min
      following nebulization of sCT solution. L-PEG and B-PEG-based microparticles were
      able to increase T(max) to 20 +/- 1 min and 18 +/- 8 min, respectively.
      Furthermore, sCT absolute bioavailability after L-PEG-based microparticle
      aerosolization at 100 MUg/kg was 2.3 times greater than for the nebulized sCT
      solution.

PMID- 21882838
TI  - In situ raman spectral mapping study on the microscale fibers in blue coral
      (Heliopora coerulea) skeletons.
AB  - The presence and localization of organic matrix associated with the aragonite
      phase in the fibers of blue coral Heliopora coerulea skeletons were studied by in
      situ microRaman mapping spectra, with a spatial resolution of ~0.3 MUm. Spatial
      variations in the amounts and chemical compositions of the fibers were imaged.
      The results showed that the amide I and the alpha-helix of amide III were
      perpendicular to the c-axis of fibers' growth, whereas the beta-turns/sheet of
      amide III was in the parallel conformation. Visible S-S and C-S bonds were
      consistent with the XANES results, which indicated the existence of organic
      sulfur in coral skeletons. Regular cyclic changes between aragonite and organic
      matrix refined a stepping growth mode of the fibers' biomineralization. An
      inorganic PO(4) bond was detected and exhibited the same concentration variation
      trends as the v(4) aragonite bands. Instead of providing an ocean P proxy on the
      subseasonal to centennial scale by LA-ICPMS, the possibility was raised of
      producing high resolution surface ocean phosphorus records on daily environmental
      variation via P/Ca variation cycles determined from Raman mapping data.

PMID- 21882839
TI  - Planar multipole ion trap/time-of-flight mass spectrometer.
AB  - We present a novel, hybrid ion trap/time-of-flight mass spectrometer that is
      based on a planar multipole design. Compared with Paul trap/time-of-flight
      instruments, this design possesses the principal advantages of higher injection
      efficiency and more homogeneous extraction fields. We demonstrate the viability
      of the concept and describe the characterization of a first prototype. Ions can
      be injected into the trap with little mass discrimination and stored for several
      minutes. A resolution of over 1300 is achieved in reflectron mode, and the
      influence of the RF amplitude and pressure on the resolution is analyzed. We
      suggest several applications in which this new instrument could offer advantages
      over existing technology.

PMID- 21882840
TI  - Composites of aminodextran-coated Fe3O4 nanoparticles and graphene oxide for
      cellular magnetic resonance imaging.
AB  - Formation of composites of dextran-coated Fe(3)O(4) nanoparticles (NPs) and
      graphene oxide (Fe(3)O(4)-GO) and their application as T(2)-weighted contrast
      agent for efficient cellular magnetic resonance imaging (MRI) are reported.
      Aminodextran (AMD) was first synthesized by coupling reaction of
      carboxymethyldextran with butanediamine, which was then chemically conjugated to
      meso-2,3-dimercaptosuccinnic acid-modified Fe(3)O(4) NPs. Next, the AMD-coated
      Fe(3)O(4) NPs were anchored onto GO sheets via formation of amide bond in the
      presence of 1-ethyl-3-(3-dimethyaminopropyl) carbodiimide (EDC). It is found that
      the Fe(3)O(4)-GO composites possess good physiological stability and low
      cytotoxicity. Prussian Blue staining analysis indicates that the Fe(3)O(4)-GO
      nanocomposites can be internalized efficiently by HeLa cells, depending on the
      concentration of the composites incubated with the cells. Furthermore, compared
      with the isolated Fe(3)O(4) NPs, the Fe(3)O(4)-GO composites show significantly
      enhanced cellular MRI, being capable of detecting cells at the iron concentration
      of 5 MUg mL(-1) with cell density of 2 * 10(5) cells mL(-1), and at the iron
      concentration of 20 MUg mL(-1) with cell density of 1000 cells mL(-1).

PMID- 21882841
TI  - Tailoring homochirality at surfaces: going beyond molecular handedness.
AB  - Chirality can be bestowed upon a surface by the adsorption of molecules and is
      usually discussed in terms of the molecular handedness. However, the adsorption
      process often leads to a new manifestation of chirality in the form of the
      adsorption footprint, which can also be chiral and generate mirror-images in 2-D.
      Therefore, in describing the chirality of the interface, one must consider both
      the handedness and the adsorption 'footedness' of the system. Specifically, the
      creation of a truly homochiral surface must ensure that a single chirality is
      expressed for each aspect, and requires not only the control of molecule
      handedness but also direct control over footedness. Here, we demonstrate the
      ability to engineer homochiral footedness by a structural modification of
      enantiopure (S)-proline, which normally creates a (4 * 2) organization on a
      Cu(110) surface with heterochiral footedness. This modification of proline via
      the addition of a double bond within the pyrrolidine ring, yielding 3-pyrroline-2
      carboxylic acid (PCA), is sufficient to drive the footprints of the entire (4 *
      2) assembly from heterochiral to homochiral, leading to the creation of a truly
      homochiral interface The effects of modifications upon the footprint arrangements
      were characterized at the single-molecule level by scanning tunnelling
      microscopy, reflection absorption infrared spectroscopy and periodic density
      functional theory calculations. The control of adsorption footprints is not only
      pivotal to tailoring chirality at surfaces but also plays a key role in dictating
      the organization, the outward facing functionalities and the response of the
      organic-inorganic interface.

PMID- 21882842
TI  - Computational high-frequency overtone spectra of the water-ammonia complex.
AB  - We have computed vibrational high-frequency overtone spectra of the water-ammonia
      complex, H(2)O-NH(3), and its isotopomers. The complex has been modeled as two
      independently vibrating monomer units. The internal coordinate Hamiltonians for
      each monomer unit have been constructed using exact gas phase kinetic energy
      operators. The potential energy and dipole moment surfaces have been calculated
      with the explicitly correlated coupled cluster method CCSD(T)-F12A and the
      valence triple-zeta VTZ-F12 basis around the equilibrium geometry of the complex.
      The vibrational eigenvalues have been calculated variationally and the
      eigenfunctions obtained have been used to compute the intensities of the
      absorption transitions. In H(2)O-NH(3), the water molecule acts as the proton
      donor and its symmetry is broken. The hydrogen-bonded OH bond oscillator
      undergoes a large redshift and intensity enhancement compared to the free
      hydrogen bond. Broken degeneracy of the asymmetric vibrations, quenched inversion
      splittings, and blueshift of the symmetric bending mode are the most visible
      changes in the ammonia unit.

PMID- 21882843
TI  - New silicon architectures by gold-assisted chemical etching.
AB  - Silicon nanowires (SiNWs) were produced by nanosphere lithography and metal
      assisted chemical etching. The combination of these methods allows the morphology
      and organization control of Si NWs on a large area. From the investigation of
      major parameters affecting the etching such as doping type, doping concentration
      of the substrate, we demonstrate the formation of new Si architectures consisting
      of organized Si NW arrays formed on a micro/mesoporous silicon layer with
      different thickness. These investigations will allow us to better understand the
      mechanism of Si etching to enable a wide range of applications such as molecular
      sensing, and for thermoelectric and photovoltaic devices.

PMID- 21882844
TI  - Evaluation of the boron tolerant grass, Puccinellia distans, as an initial
      vegetative cover for the Phytorestoration of a boron-contaminated mining site in
      Southern California.
AB  - Land damaged by boron (B) mining should be restored to its natural state with a
      zero net impact on biodiversity. In an earlier study (Environ. Sci.
      Technol.2010,44, 7089-7095), we characterized a Turkish ecotype of the grass,
      Puccinellia distans, which exhibited extreme tolerance to B. Here we evaluated
      the use of a US ecotype of P. distans as an initial vegetative cover for the
      phytorestoration of a B mine in southern California. Hydroponic studies revealed
      that this P. distans ecotype tolerated B concentrations >100 mg B/L and could be
      germinated and grown in B-contaminated soils taken from the sites to be restored.
      P. distans grew well in moderately B-contaminated soil (~88 mg B/L saturated
      extract) amended with added organic matter (peat moss); other soil treatments
      such as gypsum addition or pH correction were not needed. P. distans also grew in
      severely B-contaminated soil (~1506 mg B/L) provided that toxic levels of soil B
      were diluted by the addition of sand and/or organic matter. Our results provide
      evidence in support of the concept of using the US ecotype of P. distans as an
      initial vegetative cover for the phytorestoration of B-contaminated soil.

PMID- 21882845
TI  - Self-organization of 1-methylnaphthalene on the surface of artificial snow
      grains: a combined experimental-computational approach.
AB  - A combined experimental-computational approach was used to study the self
      organization and microenvironment of 1-methylnaphthalene (1MN) deposited on the
      surface of artificial snow grains from vapors at 238 K. The specific surface area
      of this snow (1.1 * 10(4) cm(2) g(-1)), produced by spraying very fine droplets
      of pure water from a nebulizer into liquid nitrogen, was determined using
      valerophenone photochemistry to estimate the surface coverage by 1MN.
      Fluorescence spectroscopy at 77 K, in combination with molecular dynamics
      simulations, and density functional theory (DFT) and second-order coupled cluster
      (CC2) calculations, provided evidence for the occurrence of ground- and excited
      state complexes (excimers) and other associates of 1MN on the snow grains'
      surface. Only weak excimer fluorescence was observed for a loading of 5 * 10(-6)
      mol kg(-1), which is ~2-3 orders of magnitude below monolayer coverage. However,
      the results indicate that the formation of excimers is favored at higher surface
      loadings (>5 * 10(-5) mol kg(-1)), albeit still being below monolayer coverage.
      The calculations of excited states of monomer and associated moieties suggested
      that a parallel-displaced arrangement is responsible for the excimer emission
      observed experimentally, although some other associations, such as T-shape dimer
      structures, which do not provide excimer emission, can still be relatively
      abundant at this surface concentration. The hydrophobic 1MN molecules, deposited
      on the ice surface, which is covered by a relatively flexible quasi-liquid layer
      at 238 K, are then assumed to be capable of dynamic motion resulting in the
      formation of energetically preferred associations to some extent. The
      environmental implications of organic compounds' deposition on snow grains and
      ice are discussed.

PMID- 21882846
TI  - Group additivity values for estimating the enthalpy of formation of organic
      compounds: an update and reappraisal. 1. C, H, and O.
AB  - This study examines critically the present state and utility of the Benson
      additivity schemes for estimating the enthalpy of formation of organic compounds.
      Old and new group additivity values (GAV) for a wide variety of compounds
      containing C, H and O are described and are revised where appropriate. When new
      terms are proposed, or old ones significantly altered, the rationale for so doing
      is provided. Corrections for such items as cis-isomer effects, gauche
      interactions, ring strain energies, double-bond position, conjugation effects,
      steric hindrance in aromatic molecules, etc. are included and discussed. Also
      provided are the thermochemical consequences of functional group replacements, in
      which one group in a molecule is substituted by another, thus providing quick
      short cuts to estimating new Delta(f)H(0) values. Results derived from the new
      additivity terms are consistent with those produced by computational chemistry
      methods in general use.

PMID- 21882847
TI  - Exploration of the topology of chemical spaces with network measures.
AB  - Discontinuous changes in molecular structure (resulting from continuous
      transformations of molecular coordinates) lead to changes in chemical properties
      and biological activities that chemists attempt to describe through structure
      activity or structure-property relationships (QSAR/QSPR). Such relationships are
      commonly envisioned in a continuous high-dimensional space of numerical
      descriptors, referred to as chemistry space. The choice of descriptors defining
      coordinates within chemistry space and the choice of similarity metrics thus
      influence the partitioning of this space into regions corresponding to local
      structural similarity. These are the regions (known as domains of applicability)
      most likely to be successfully modeled by a structure-activity relationship. In
      this work the network topology and scaling relationships of chemistry spaces are
      first investigated independent of a specific biological activity. Chemistry
      spaces studied include the ZINC data set, a qHTS PubChem bioassay, as well as the
      space of protein binding sites from the PDB. The characteristics of these
      networks are compared and contrasted with those of the bioassay SALI subnetwork,
      which maps discontinuities or cliffs in the structure-activity landscape. Mapping
      the locations of activity cliffs and comparing the global characteristics of SALI
      subnetworks with those of the underlying chemistry space networks generated using
      different representations, can guide the choice of a better representation. A
      higher local density of SALI edges with a particular representation indicates a
      more challenging structure-activity relationship using that fingerprint in that
      region of chemistry space.

PMID- 21882848
TI  - Annual variation of natural 15N abundance in tea leaves and its practicality as
      an organic tea indicator.
AB  - To obtain basic knowledge about the relationship between the application of
      organic fertilizers and the delta15N values of leaves of organically grown tea
      plants, annual variations in the delta15N values of the tea leaves were
      investigated. Although variations did not immediately arise after the application
      of organic fertilizers, differences in the delta15N values between organic and
      conventional cultivations appeared basically after three years from the beginning
      of the organic cultivation except when an organic fertilizer with a low delta15N
      value was applied, and the variation depended on the delta15N values of the
      fertilizers. In addition, the effectiveness of the delta15N values as a practical
      indicator of organic teas was examined. The tea leaves collected from organic
      farms did not always have higher delta15N values than the commercially available
      nonorganic teas. This result demonstrates that it is not easy to discriminate
      organic teas from nonorganic teas simply by their delta15N values.

PMID- 21882849
TI  - Restructuring of hydrophobic surfaces created by surfactant adsorption to mica
      surfaces.
AB  - Hydrophobic surfaces created by the adsorption of a monolayer of surfactants,
      such as CTAB or DODAB, to mica display long-range mutual attraction when placed
      in water. Initially, this attraction was considered to be due to hydrophobic
      interaction, but more careful measurements using AFM showed that the surfactant
      monolayer undergoes rearrangements to produce charged patches on the surface;
      therefore, the nature of the long-range interaction is due to the electrostatic
      interaction between patches. The monolayer rearrangement depends on the nature of
      the surfactant and its counterion. To study possible monolayer rearrangements in
      molecular detail, we performed detailed molecular dynamics computer simulations
      on systems containing a monolayer of surfactants RN(CH(3))(3)(+)Cl(-) (R
      indicates a saturated hydrocarbon chain) adsorbed on a mica surface and immersed
      in water. We observe that when chain R is 18 carbons long the monolayer
      rearranges into a micelle but it remains a monolayer when the chain contains 24
      carbons.

PMID- 21882850
TI  - Designed hybridization properties of DNA-gold nanoparticle conjugates for the
      ultraselective detection of a single-base mutation in the breast cancer gene
      BRCA1.
AB  - We have investigated the hybridization properties of DNA-gold nanoparticle
      conjugates and have discovered that the hybridization properties are dramatically
      affected by controlling various synthetic and environmental conditions. We have
      further demonstrated that moderate DNA loading instead of high loading per
      nanoparticle significantly enhances the hybridization rates of DNA-gold
      nanoparticle conjugates, which allows one to precisely design their hybridization
      properties to distinguish a single-nucleotide polymorphism (SNP). A diagnostic
      application for the colorimetric detection of an SNP associated with a mutation
      in the breast cancer gene BRCA1 has been carefully designed and demonstrated.

PMID- 21882851
TI  - Genomic profiling of microRNAs and proteomics reveals an early molecular
      alteration associated with tumorigenesis induced by MC-LR in mice.
AB  - Studies have demonstrated that microcystins (MCs) can act as potential
      carcinogens and have caused serious risk to public environmental health. The
      molecular mechanisms of MC-induced susceptibility to carcinogenesis are largely
      unknown. In this study, we performed for the first time a comprehensive analysis
      of changes in microRNAs (miRNAs) and proteins expression in livers of mice
      treated with MC-LR. Utilizing microarray and two-dimensional gel electrophoresis
      (2-DE) analysis, we identified 37 miRNAs and 42 proteins significantly altered.
      Many aberrantly expressed miRNAs were related to various cancers (e.g., miR-125b,
      hepatocellular carcinoma; miR-21, leukemia; miR-16, chronic lymphocytic leukemia;
      miR-192, pituitary adenomas; miR-199a-3p, ovarian cancer; miR-34a, pancreatic
      cancer). Several miRNAs (e.g., miR-34a, miR-21) and proteins (e.g., TGM2, NDRG2)
      that play crucial roles in liver tumorigenesis were first found to be affected by
      MC-LR in mouse liver. MC-LR also altered the expression of a number of miRNAs and
      proteins involved in several pathways related to tumorigenesis, such as
      glutathione metabolism, VEGF signaling, and MAPK signaling pathway. Integration
      of post-transcriptomics, proteomics, and transcriptomics reveals that the
      networks miRNAs and their potential target genes and proteins involved in had a
      close association with carcinogenesis. These results provide an early molecular
      mechanism for liver tumorigenesis induced by MCs.

PMID- 21882852
TI  - Structural changes of carotenoid astaxanthin in a single algal cell monitored in
      situ by Raman spectroscopy.
AB  - The changes of structure of astaxanthin (AXT), a superpotent antioxidant, upon
      thermal stress were investigated in unicellular microalgae Haematococcus
      pluvialis by measuring Raman spectra in situ and analyzing obtained results with
      DFT calculations. Although no visual changes are observed in the Haematococcus
      cells upon heating, discernible changes in Raman spectra occur from -100  degrees
      C systematically up to 150  degrees C. The exponential increase of the Raman
      shift of the nu C?C band at ca. 1520 cm(-1) along with the change of the
      intensity ratio of bands at 1190 and 1160 cm(-1) is observed, that correlates
      with the changes predicted by calculations for astaxanthin conformers ordered by
      decreasing energy. It is assumed that AXT molecules, initially in the form of H
      aggregates with the trans conformations of the end-rings, interconvert toward
      more stable gauche forms upon thermal stress of the algae. The applied approach
      enables one to follow structural changes of the carotenoid upon temperature
      stress both in a single algal cell and in a multicellular sample in situ.
      Obtained information might be of use to improve the industrial process of
      extraction of AXT in its most bioavailable form.

PMID- 21882853
TI  - Measurement of heterogeneous reaction rates: three strategies for controlling
      mass transport and their application to indium-mediated allylations.
AB  - We describe three new strategies for determining heterogeneous reaction rates
      using photomicroscopy to measure the rate of retreat of metal surfaces: (i)
      spheres in a stirred solution, (ii) microscopic powder in an unstirred solution,
      and (iii) spheres on a rotating shaft. The strategies are applied to indium
      mediated allylation (IMA), which is a powerful tool for synthetic chemists
      because of its stereoselectivity, broad applicability, and high yields. The rate
      limiting step of IMA, reaction of allyl halides at indium metal surfaces, is
      shown to be fast, with a minimum value of the heterogeneous rate constant of 1 *
      10(-2) cm/s, an order of magnitude faster than the previously determined minimum
      value. The strategies described here can be applied to any reaction in which the
      surface is retreating or advancing, thereby broadening the applicability of
      photomicroscopy to measuring heterogeneous reaction kinetics.

PMID- 21882854
TI  - High dynamic range bio-molecular ion microscopy with the Timepix detector.
AB  - Highly parallel, active pixel detectors enable novel detection capabilities for
      large biomolecules in time-of-flight (TOF) based mass spectrometry imaging (MSI).
      In this work, a 512 * 512 pixel, bare Timepix assembly combined with chevron
      microchannel plates (MCP) captures time-resolved images of several m/z species in
      a single measurement. Mass-resolved ion images from Timepix measurements of
      peptide and protein standards demonstrate the capability to return both mass
      spectral and localization information of biologically relevant analytes from
      matrix-assisted laser desorption ionization (MALDI) on a commercial ion
      microscope. The use of a MCP-Timepix assembly delivers an increased dynamic range
      of several orders of magnitude. The Timepix returns defined mass spectra already
      at subsaturation MCP gains, which prolongs the MCP lifetime and allows the gain
      to be optimized for image quality. The Timepix peak resolution is only limited by
      the resolution of the in-pixel measurement clock. Oligomers of the protein
      ubiquitin were measured up to 78 kDa.

PMID- 21882855
TI  - Gold(III)-catalyzed direct acetoxylation of arenes with iodobenzene diacetate.
AB  - AuCl(3)-catalyzed direct acetoxylation of electron-rich aromatic compounds has
      been achieved with iodobenzene diacetate as the acetoxylation reagent.

PMID- 21882857
TI  - Cathode composites for Li-S batteries via the use of oxygenated porous
      architectures.
AB  - Li-S rechargeable batteries are attractive for electric transportation because of
      their low cost, environmentally friendliness, and superior energy density.
      However, the Li-S system has yet to conquer the marketplace, owing to its
      drawbacks, namely, soluble polysulfide formation. To tackle this issue, we
      present here a strategy based on the use of a mesoporous chromium trimesate metal
      organic framework (MOF) named MIL-100(Cr) as host material for sulfur
      impregnation. Electrodes containing sulfur impregnated within the pores of the
      MOF were found to show a marked increase in the capacity retention of Li-S
      cathodes. Complementary transmission electron microscopy and X-ray photoelectron
      spectroscopy measurements demonstrated the reversible capture and release of the
      polysulfides by the pores of MOF during cycling and evidenced a weak binding
      between the polysulphides and the oxygenated framework. Such an approach was
      generalized to other mesoporous oxide structures, such as mesoporous silica, for
      instance SBA-15, having the same positive effect as the MOF on the capacity
      retention of Li-S cells. Besides pore sizes, the surface activity of the
      mesoporous additives, as observed for the MOF, appears to also have a pronounced
      effect on enhancing the cycle performance. Increased knowledge about the
      interface between polysulfide species and oxide surfaces could lead to novel
      approaches in the design and fabrication of long cycle life S electrodes.

PMID- 21882858
TI  - Universally applicable model for the quantitative determination of lake sediment
      composition using fourier transform infrared spectroscopy.
AB  - Fourier transform infrared spectroscopy (FTIRS) can provide detailed information
      on organic and minerogenic constituents of sediment records. Based on a large
      number of sediment samples of varying age (0-340,000 yrs) and from very diverse
      lake settings in Antarctica, Argentina, Canada, Macedonia/Albania, Siberia, and
      Sweden, we have developed universally applicable calibration models for the
      quantitative determination of biogenic silica (BSi; n = 816), total inorganic
      carbon (TIC; n = 879), and total organic carbon (TOC; n = 3164) using FTIRS.
      These models are based on the differential absorbance of infrared radiation at
      specific wavelengths with varying concentrations of individual parameters, due to
      molecular vibrations associated with each parameter. The calibration models have
      low prediction errors and the predicted values are highly correlated with
      conventionally measured values (R = 0.94-0.99). Robustness tests indicate the
      accuracy of the newly developed FTIRS calibration models is similar to that of
      conventional geochemical analyses. Consequently FTIRS offers a useful and rapid
      alternative to conventional analyses for the quantitative determination of BSi,
      TIC, and TOC. The rapidity, cost-effectiveness, and small sample size required
      enables FTIRS determination of geochemical properties to be undertaken at higher
      resolutions than would otherwise be possible with the same resource allocation,
      thus providing crucial sedimentological information for climatic and
      environmental reconstructions.

PMID- 21882859
TI  - Reactive molecular dynamics study on the first steps of DNA damage by free
      hydroxyl radicals.
AB  - We employ a large scale molecular simulation based on bond-order ReaxFF to
      simulate the chemical reaction and study the damage to a large fragment of DNA
      molecule in the solution by ionizing radiation. We illustrate that the randomly
      distributed clusters of diatomic OH radicals that are primary products of
      megavoltage ionizing radiation in water-based systems are the main source of
      hydrogen abstraction as well as formation of carbonyl and hydroxyl groups in the
      sugar moiety that create holes in the sugar rings. These holes grow up slowly
      between DNA bases and DNA backbone, and the damage collectively propagates to a
      DNA single and double strand break.

PMID- 21882860
TI  - Thermoelectricity in fullerene-metal heterojunctions.
AB  - Thermoelectricty in heterojunctions, where a single-molecule is trapped between
      metal electrodes, has been used to understand transport properties at organic
      inorganic interfaces. (1)  The transport in these systems is highly dependent on
      the energy level alignment between the molecular orbitals and the Fermi level (or
      work function) of the metal contacts. To date, the majority of single-molecule
      measurements have focused on simple small molecules where transport is dominated
      through the highest occupied molecular orbital. (2, 3)  In these systems, energy
      level alignment is limited by the absence of electrode materials with low Fermi
      levels (i.e., large work functions). Alternatively, more controllable alignment
      between molecular orbitals and the Fermi level can be achieved with molecules
      whose transport is dominated by the lowest unoccupied molecular orbital (LUMO)
      because of readily available metals with lower work functions. Herein, we report
      molecular junction thermoelectric measurements of fullerene molecules (i.e.,
      C(60), PCBM, and C(70)) trapped between metallic electrodes (i.e., Pt, Au, Ag).
      Fullerene junctions demonstrate the first strongly n-type molecular thermopower
      corresponding to transport through the LUMO, and the highest measured magnitude
      of molecular thermopower to date. While the electronic conductance of fullerenes
      is highly variable, due to fullerene's variable bonding geometries with the
      electrodes, the thermopower shows predictable trends based on the alignment of
      the LUMO with the work function of the electrodes. Both the magnitude and trend
      of the thermopower suggest that heterostructuring organic and inorganic materials
      at the nanoscale can further enhance thermoelectric performance, therein
      providing a new pathway for designing thermoelectric materials.

PMID- 21882861
TI  - New electrophilic addition of alpha-diazoesters with ketones for enantioselective
      C-N bond formation.
AB  - alpha-Diazoesters were discovered to be good electrophiles in a catalytic
      asymmetric alpha-functionalization of ketones for the first time. This reaction
      also provided a direct and efficient method for C-N bond formation with excellent
      yields (up to 98%) and enantioselectivities (up to 99% ee) under mild conditions.
      The application of the electrophilicity of alpha-diazoesters opens up a novel way
      to access the diversity of diazo chemistry.

PMID- 21882863
TI  - Bonding and magnetic response properties of several toroid structures. Insights
      of the role of Ni2S2 as a building block from relativistic density functional
      theory calculations.
AB  - Relativistic density functional calculations were carried out on several nickel
      toroid mercaptides of the general formula [Ni(MU-SR)(2)](n), with the aim to
      characterize and analyze their stability and magnetic response properties, in
      order to gain more insights into their stabilization and size-dependent behavior.
      The Ni-ligand interaction has been studied by means projected density of states
      and energy decomposition analysis, which denotes its stabilizing character. The
      graphical representation of the response to an external magnetic field is applied
      for the very first time taking into account the spin-orbit term. This map allows
      one to clearly characterize the magnetic behavior inside and in the closeness of
      the toroid structure showing the prescence of paratropic ring currents inside the
      Ni(n) ring, and by contrast, diatropic currents confined in each Ni(2)S(2) motif
      denoting an aromatic behavior (in terms of magnetic criteria). The calculated
      data suggests that the Ni(2)S(2) moiety can be regarded as a stable constructing
      block, which can afford several toroid structures of different nuclearities in
      agreement with that reported in the experimental literature. In addition, the
      effects of the relativistic treatment over the magnetic response properties on
      these lighter compounds are denoted by comparing nonrelativistic, scalar
      relativistic, and scalar plus spin-orbit relativistic treatments, showing their
      acting, although nonpronunced, role.

PMID- 21882862
TI  - Analysis of hemoglobin adducts from acrylamide, glycidamide, and ethylene oxide
      in paired mother/cord blood samples from Denmark.
AB  - The knowledge about fetal exposure to acrylamide/glycidamide from the maternal
      exposure through food is limited. Acrylamide, glycidamide, and ethylene oxide are
      electrophiles and form adducts with hemoglobin (Hb), which could be used for in
      vivo dose measurement. In this study, a method for analysis of Hb adducts by
      liquid chromatography-mass spectrometry, the adduct FIRE procedure, was applied
      to measurements of adducts from these compounds in maternal blood samples (n =
      87) and umbilical cord blood samples (n = 219). The adduct levels from the three
      compounds, acrylamide, glycidamide, and ethylene oxide, were increased in tobacco
      smokers. Highly significant correlations were found between cord and maternal
      blood with regard to measured adduct levels of the three compounds. The mean
      cord/maternal hemoglobin adduct level ratios were 0.48 (range 0.27-0.86) for
      acrylamide, 0.38 (range 0.20-0.73) for glycidamide, and 0.43 (range 0.17-1.34)
      for ethylene oxide. In vitro studies with acrylamide and glycidamide showed a
      lower (0.38-0.48) rate of adduct formation with Hb in cord blood than with Hb in
      maternal blood, which is compatible with the structural differences in fetal and
      adult Hb. Together, these results indicate a similar life span of fetal and
      maternal erythrocytes. The results showed that the in vivo dose in fetal and
      maternal blood is about the same and that the placenta gives negligible
      protection of the fetus to exposure from the investigated compounds. A trend of
      higher levels of the measured adducts in cord blood with gestational age was
      observed, which may reflect the gestational age-related change of the cord blood
      Hb composition toward a higher content of adult Hb. The results suggest that the
      Hb adduct levels measured in cord blood reflect the exposure to the fetus during
      the third trimester. The evaluation of the new analytical method showed that it
      is suitable for monitoring of background exposures of the investigated
      electrophilic compounds in large population studies.

PMID- 21882864
TI  - Atomistic molecular dynamics simulations of the interactions of oleic and 2
      hydroxyoleic acids with phosphatidylcholine bilayers.
AB  - Fatty oleic acid (OA) and, recently, its derivative 2-hydroxyoleic acid (2OHOA)
      have been reported to display an important therapeutic activity. To understand
      better these therapeutic effects at the molecular and cellular levels, in this
      work we have carried out molecular dynamics simulations to elucidate the
      structural and dynamical changes taking place in model 1,2-dimyristoyl-sn-glycero
      3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)
      bilayers upon insertion of rising concentrations of these two fatty acids. The
      simulations are performed using a united-atoms model to describe both the
      phospholipids and the fatty acids. The process of insertion of the fatty acids
      from the aqueous phase into the bilayers is simulated first, showing that it is
      feasible and may lead to some degree of phase separation within the bilayer. The
      interactions of the embedded homogeneously dispersed fatty acids with the
      phospholipid chains of the bilayers are then simulated at different
      concentrations of the fatty acids. The results from these simulations show that
      accumulation of OA and 2OHOA up to high concentrations induces only small
      structural changes in the bilayers. An increase of the mobility of the lipid and
      fatty acid chains at rising fatty acid concentrations is also observed, which is
      more marked for the fatty acid chains, along with an enhancement of the
      permeability of the bilayers to the hydrophobic penetrant.

PMID- 21882865
TI  - Enantiomer fractions of chiral Perfluorooctanesulfonate (PFOS) in human sera.
AB  - Perfluorooctane sulfonate (PFOS) is the most prominent perfluoroalkyl contaminant
      in humans and wildlife, but there is great uncertainty in exposure pathways,
      particularly with respect to the importance of PFOS-precursors (PreFOS). We
      explored the hypothesis that nonracemic proportions of chiral PFOS in serum are
      qualitative and semiquantitative biomarkers of human PreFOS exposure. A new
      chiral HPLC-MS/MS method was developed for alpha-perfluoromethyl branched PFOS
      (1m-PFOS, typically 2-3% of total PFOS) and applied to enantiomer fraction (EF)
      analysis in biological samples. In blood and tissues of rodents exposed
      subchronically to electrochemical PFOS, 1m-PFOS was racemic (EF = 0.485-0.511)
      and no evidence for enantioselective excretion was found in this model mammal. 1m
      PFOS in serum of pregnant women, from Edmonton, was significantly nonracemic,
      with a mean EF (+/-standard deviation) of 0.432 +/- 0.009, similar to pooled
      North American serum. In a highly exposed Edmonton family (mother, father, and 5
      children) living in a house where ScotchGard had been applied repeatedly to
      carpet and upholstery, EFs ranged from 0.35 to 0.43, significantly more
      nonracemic than in pregnant women. Semiquantitative estimates of % serum 1m-PFOS
      coming from 1m-PreFOS biotransformation in both subpopulations were in reasonable
      agreement with model predictions of human exposure to PFOS from PreFOS. The data
      were overall suggestive that the measured nonracemic EFs were influenced by the
      relative extent of exposure to PreFOS. The possibility of using 1m-PFOS EFs for
      assessing the relative contribution of 1m-PreFOS (or PreFOS in general) in
      biological samples requires further application before being fully validated, but
      could be a powerful tool for probing general sources of PFOS in environments
      where the importance of PreFOS is unknown.

PMID- 21882866
TI  - Thermodynamic analysis of self-assembly in coiled-coil biomaterials.
AB  - Coiled-coil protein structural motifs have proven amenable to the design of
      structurally well-defined biomaterials. Mesoscale structural properties can be
      fairly well predicted based on rules governing the chemical interactions between
      the helices that define this structural motif. We explore the role of the
      hydrophobic core residues on the self-assembly of a coiled-coil polymer through a
      mutational analysis coupled with a salting-out procedure. Because the resultant
      polymers remain in solution, a thermodynamic approach is applied to characterize
      the polymer assembly using conventional equations from polymer theory to extract
      nucleation and elongation parameters. The stabilities and lengths of the polymers
      are measured using circular dichroism spectropolarimetry, sizing methods
      including dynamic light scattering and analytical ultracentrifugation, and atomic
      force microscopy to assess mesoscale morphology. Upon mutating isoleucines at two
      core positions to serines, we find that polymer stability is decreased while the
      degree of polymerization is about the same. Differences in results from circular
      dichroism and dynamic light scattering experiments suggest the presence of a
      stable intermediate state, and a scheme is proposed for how this intermediate
      might relate to the monomer and polymer states.

PMID- 21882867
TI  - Counter anion effect on the self-aggregation of dimethyl-di-N-octylammonium
      cation: a dual behavior between hydrotropes and surfactants.
AB  - Self-aggregation of eight dimethyl-di-N-octylammonium salts ([DiC(8)]) has been
      investigated as a function of the nature of the counteranion. Tensiometry,
      conductimetry, and [DiC(8)]-selective electrode measurements highlighted three
      different behaviors and led to a rationalization of the aggregation process
      depending on the counteranion: "hydrophilic" anions (MoO(4)(2-), WO(4)(2-),
      SO(4)(2-), F(-)) give only unimers and micelles, whereas less hydrated anions
      form unimers, dimers, and either one micelle-like structure (NO(3)(-), Br(-)) or
      two micelle-like structures (CH(3)SO(3)(-), Cl(-)). Small-angle neutron and
      dynamic light scattering confirms the unusual behavior of [DiC(8)][Cl], which
      forms two types of aggregates: (i) disk or vesicles between 10 and 30 mM and (ii)
      ellipsoidal micelles above 30 mM. For [DiC(8)][MoO(4)(2-)], the formation of
      ellipsoidal micelles is supported between 10 and 300 mM. Finally, shapes and
      sizes of the aggregates are confirmed by molecular dynamic experiments.

PMID- 21882869
TI  - Increasing the thermal storage capacity of a phase change material by
      encapsulation: preparation and application in natural rubber.
AB  - Existing encapsulated organic phase change materials (PCM) usually contain a
      shell material that possesses a poor heat storage capacity and so results in a
      lowered latent heat storage density of the encapsulated PCM compared to
      unencapsulated PCM. Here, we demonstrate the use of a novel microencapsulation
      process to encapsulate n-eicosane (C20) into a 2:1 (w/w) ratio blend of ethyl
      cellulose (EC):methyl cellulose (MC) to give C20-loaded EC/MC microspheres with
      an increased heat storage capacity compared to the unencapsulated C20. Up to a 29
      and 24% increase in the absolute enthalpy value during crystallization and
      melting were observed for the encap-C20/EC/MC microparticles with a 9% (w/w)
      EC/MC polymer content. The mechanism that leads to the increased latent heat
      storage capacity is discussed. The blending of the water-dispersible C20-loaded
      EC/MC microspheres into natural rubber latex showed excellent compatibility, and
      the obtained rubber composite showed not only an obvious thermoregulation
      property but also an improved mechanical property.

PMID- 21882868
TI  - Bacterial self-resistance to the natural proteasome inhibitor salinosporamide A.
AB  - Proteasome inhibitors have recently emerged as a therapeutic strategy in cancer
      chemotherapy, but susceptibility to drug resistance limits their efficacy. The
      marine actinobacterium Salinispora tropica produces salinosporamide A (NPI-0052,
      marizomib), a potent proteasome inhibitor and promising clinical agent in the
      treatment of multiple myeloma. Actinobacteria also possess 20S proteasome
      machinery, raising the question of self-resistance. We identified a redundant
      proteasome beta-subunit, SalI, encoded within the salinosporamide biosynthetic
      gene cluster and biochemically characterized the SalI proteasome complex. The
      SalI beta-subunit has an altered substrate specificity profile, 30-fold
      resistance to salinosporamide A, and cross-resistance to the FDA-approved
      proteasome inhibitor bortezomib. An A49V mutation in SalI correlates to clinical
      bortezomib resistance from a human proteasome beta5-subunit A49T mutation,
      suggesting that intrinsic resistance to natural proteasome inhibitors may predict
      clinical outcomes.

PMID- 21882870
TI  - Toxicity and reductions in intracellular calcium levels following uptake of a
      tetracycline antibiotic in Arabidopsis.
AB  - Plant responses to natural stresses have been the focus of numerous studies;
      however less is known about plant responses to artificial (i.e., man-made)
      stress. Chlortetracycline (CTC) is widely used in agriculture and becomes an
      environmental contaminant when introduced into soil from manure used as
      fertilizer. We show here that in the model plant Arabidopsis (Arabidopsis
      thaliana), root uptake of CTC leads to toxicity, with growth reductions and other
      effects. Analysis of protein accumulation and in vivo synthesis revealed numerous
      changes in soluble and membrane-associated proteins in leaves and roots. Many
      representative proteins associated with different cellular processes and
      compartments showed little or no change in response to CTC. However, differences
      in accumulation and synthesis of NAD-malic enzyme in leaves versus roots suggest
      potential CTC-associated effects on metabolic respiration may vary in different
      tissues. Fluorescence resonance energy transfer (FRET) analysis indicated reduced
      levels of intracellular calcium are associated with CTC uptake and toxicity.
      These findings support a model in which CTC uptake through roots leads to
      reductions in levels of intracellular calcium due to chelation. In turn, changes
      in overall patterns and levels of protein synthesis and accumulation due to
      reduced calcium ultimately lead to growth reductions and other toxicity effects.

PMID- 21882871
TI  - Electrically induced colloidal clusters for generating shear mixing and
      visualizing flow in microchannels.
AB  - When aqueous suspensions of 1 MUm, negatively charged polystyrene particles are
      subject to a 1 kHz alternating electric field of strength greater than 7 kV(rms)
      m(-1), dynamic elliptical clusters of particles spontaneously form. With
      potential applications in microchannel fluidics in mind, we characterize how
      cluster formation and particle circulation, driven by induced dipole-dipole
      interactions, is critically dependent on time, field strength, electrolyte
      concentration, and cell thickness. Logarithmic growth of cluster size is
      observed, and particle velocity within the clusters is found to be proportional
      to cluster length. Increasing cell thickness from 10 to 60 MUm increases the
      projected cluster area but decreases cluster aspect ratio as the result of
      changing particle dispersal rates. Clusters are shown to generate significant
      fluid shear suitable for microchannel mixing applications. These clusters are
      observed to distort under transverse fluid flow and, above a critical flow rate,
      to undergo a transition to form regularly spaced particle streams, which may be
      suitable for two-dimensional visualization of fluid flow.

PMID- 21882872
TI  - Compositionally tunable Cu2ZnSn(S(1-x)Se(x))4 nanocrystals: probing the effect of
      Se-inclusion in mixed chalcogenide thin films.
AB  - Nanocrystals of multicomponent chalcogenides, such as Cu(2)ZnSnS(4) (CZTS), are
      potential building blocks for low-cost thin-film photovoltaics (PVs). CZTS PV
      devices with modest efficiencies have been realized through postdeposition
      annealing at high temperatures in Se vapor. However, little is known about the
      precise role of Se in the CZTS system. We report the direct solution-phase
      synthesis and characterization of Cu(2)ZnSn(S(1-x)Se(x))(4) nanocrystals (0 <= x
      <= 1) with the aim of probing the role of Se incorporation into CZTS. Our results
      indicate that increasing the amount of Se increases the lattice parameters,
      slightly decreases the band gap, and most importantly increases the electrical
      conductivity of the nanocrystals without a need for annealing.

PMID- 21882873
TI  - Electrochemical mechanism of ion-ionophore recognition at plasticized polymer
      membrane/water interfaces.
AB  - Here, we report on the first electrochemical study that reveals the kinetics and
      molecular level mechanism of heterogeneous ion-ionophore recognition at
      plasticized polymer membrane/water interfaces. The new kinetic data provide
      greater understanding of this important ion-transfer (IT) process, which
      determines various dynamic characteristics of the current technologies that
      enable highly selective ion sensing and separation. The theoretical assessment of
      the reliable voltammetric data confirms that the dynamics of the ionophore
      facilitated IT follows the one-step electrochemical (E) mechanism controlled by
      ion-ionophore complexation at the very interface in contrast to the
      thermodynamically equivalent two-step electrochemical-chemical (EC) mechanism
      based on the simple transfer of an aqueous ion followed by its complexation in
      the bulk membrane. Specifically, cyclic voltammograms of Ag(+), K(+), Ca(2+),
      Ba(2+), and Pb(2+) transfers facilitated by highly selective ionophores are
      measured and analyzed numerically using the E mechanism to obtain standard IT
      rate constants in the range of 10(-2) to 10(-3) cm/s at both plasticized
      poly(vinyl chloride) membrane/water and 1,2-dichloroethane/water interfaces. We
      demonstrate that these strongly facilitated IT processes are too fast to be
      ascribed to the EC mechanism. Moreover, the little effect of the viscosity of
      nonaqueous media on the IT kinetics excludes the EC mechanism, where the kinetics
      of simple IT is viscosity-dependent. Finally, we employ molecular level models
      for the E mechanism to propose three-dimensional ion-ionophore complexation at
      the two-dimensional interface as the unique kinetic requirement for the
      thermodynamically facilitated IT.

PMID- 21882874
TI  - Synthesis, properties, and applications of oligonucleotides containing an RNA
      dinucleotide phosphorothiolate linkage.
AB  - RNA represents a prominent class of biomolecules. Present in all living systems,
      RNA plays many essential roles in gene expression, regulation, and development.
      Accordingly, many biological processes depend on the accurate enzymatic
      processing, modification, and cleavage of RNA. Understanding the catalytic
      mechanisms of these enzymes therefore represents an important goal in defining
      living systems at the molecular level.  In this context, RNA molecules bearing 3'
      or 5'-S-phosphorothiolate linkages comprise what are arguably among the most
      incisive mechanistic probes available. They have been instrumental in showing
      that RNA splicing systems are metalloenzymes and in mapping the ligands that
      reside within RNA active sites. The resulting models have in turn verified the
      functional relevance of crystal structures. In other cases, phosphorothiolates
      have offered an experimental strategy to circumvent the classic problem of
      kinetic ambiguity; mechanistic enzymologists have used this tool to assign
      precise roles to catalytic groups as general acids or bases. These insights into
      macromolecular function are enabled by the synthesis of nucleic acids bearing
      phosphorothiolate linkages and the unique chemical properties they impart. In
      this Account, we review the synthesis, properties, and applications of
      oligonucleotides and oligodeoxynucleotides containing an RNA dinucleotide
      phosphorothiolate linkage.  Phosphorothioate linkages are structurally very
      similar to phosphorothiolate linkages, as reflected in the single letter of
      difference in nomenclature. Phosphorothioate substitutions, in which sulfur
      replaces one or both nonbridging oxygens within a phosphodiester linkage, are now
      widely available and are used routinely in numerous biochemical and medicinal
      applications. Indeed, synthetic phosphorothioate linkages can be introduced
      readily via a sulfurization step programmed into automated solid-phase
      oligonucleotide synthesizers.  In contrast, phosphorothiolate oligonucleotides,
      in which sulfur replaces a specific 3'- or 5'-bridging oxygen, have presented a
      more difficult synthetic challenge, requiring chemical alterations to the
      attached sugar moiety. Here we begin by outlining the synthetic strategies used
      to access these phosphorothiolate RNA analogues. The Arbuzov reaction and
      phosphoramidite chemistry are often brought to bear in creating either 3'- or 5'
      S-phosphorothiolate dinucleotides. We then summarize the responses of the
      phosphorothiolate derivatives to chemical and enzymatic cleavage agents, as well
      as mechanistic insights their use has engendered. They demonstrate particular
      utility as probes of metal-ion-dependent phosphotransesterification, general acid
      base-catalyzed phosphotransesterification, and rate-limiting chemistry. The 3'-
      and 5'-S-phosphorothiolates have proven invaluable in elucidating the mechanisms
      of enzymatic and nonenzymatic phosphoryl transfer reactions. Considering that RNA
      cleavage represents a fundamental step in the maturation, degradation, and
      regulation of this important macromolecule, the significant synthetic challenges
      that remain offer rich research opportunities.

PMID- 21882875
TI  - One product, two pathways: initially divergent radical reactions reconverge to
      form a single product in high yield.
AB  - The paper describes examples of net diastereotopic-group-selective radical
      processes having the unusual feature that a single product is formed even though
      the key reaction of the two diastereotopic radical precursors is nonselective.
      For example, reaction of (R)-N-(cyclohex-2-en-1-yl)-N-(2,6-diiodo-4
      methylphenyl)acetamide with tributyltin hydride produces 1-((4aR,9aR)-6-methyl
      2,3,4,4a-tetrahydro-1H-carbazol-9(9aH)-yl)ethanone with high product selectivity
      and in high yield. Analysis of the concentration profiles of the closed-shell
      intermediates at the halfway point of the reaction shows that nonselective
      abstraction of diastereotopic iodides by tin radicals occurs, leading to
      diastereomeric aryl radicals. These isomeric intermediates evolve via two
      nonintersecting reaction pathways, cyclization and bimolecular trapping or vice
      versa, into the same final product. Origins of the selectivity are suggested on
      the basis of conformational analysis of the products using both X-ray
      crystallography and density functional theory calculations.

PMID- 21882876
TI  - A powerful approach for the selection of 2-aminopurine substitution sites to
      investigate RNA folding.
AB  - A precise tertiary structure must be adopted to allow the function of many RNAs
      in cells. Accordingly, increasing resources have been devoted to the elucidation
      of RNA structures and the folding of RNAs. 2-Aminopurine (2AP), a fluorescent
      nucleobase analogue, can be substituted in strategic positions of DNA or RNA
      molecules to act as site-specific probe to monitor folding and folding dynamics
      of nucleic acids. Recent studies further demonstrated the potential of 2AP
      modifications in the assessment of folding kinetics during ligand-induced
      secondary and tertiary RNA structure rearrangements. However, an efficient way to
      unambiguously identify reliable positions for 2AP sensors is as yet unavailable
      and would represent a major asset, especially in the absence of crystallographic
      or NMR structural data for a target molecule. We report evidence of a novel and
      direct correlation between the 2'-OH flexibility of nucleotides, observed by
      selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) probing and
      the fluorescence response following nucleotide substitutions by 2AP. This
      correlation leads to a straightforward method, using SHAPE probing with benzoyl
      cyanide, to select appropriate nucleotide sites for 2AP substitution. This clear
      correlation is presented for three model RNAs of biological significance: the SAM
      II, adenine (addA), and preQ(1) class II (preQ(1)cII) riboswitches.

PMID- 21882877
TI  - Binary mixtures of cationic and anionic microgels.
AB  - Colloidal behaviors of binary mixtures composed of cationic and anionic microgels
      are reported. Both microgels were synthesized by aqueous free radical
      precipitation polymerization using N-isopropylacrylamide and N,N'
      methylenebisacrylamide but using different types of water-soluble initiators and
      comonomer. Effects of temperature and salt concentration on phase behaviors of
      binary mixtures of cationic and anionic microgels were investigated as well as
      single-species microgels by UV-vis spectroscopy. We found that the presence of a
      small amount of NaCl altered the dispersing behavior of the binary mixtures of
      cationic and anionic microgels when they were in hydrated and swollen states. In
      particular, scanning electron microscope observation clarified that the binary
      mixtures containing a small amount of NaCl were not flocculated, and microgels
      showed non-close-packed structures on a planar substrate in the dry state.
      Furthermore, flocculations formed when both microgels were in the swollen states
      could be redispersed by adding a small amount of NaCl and gently stirring. These
      tunable properties have not been observed in mixtures of hard particles, and are
      due to the coexistence of electrostatic interactions and steric hindrance of
      highly hydrated soft particles.

PMID- 21882878
TI  - Bifunctional nanoparticles with fluorescence and magnetism via surface-initiated
      AGET ATRP mediated by an iron catalyst.
AB  - Fluorescent/magnetic nanoparticles are of interest in many applications in
      biotechnology and nanomedicine for its living detection. In this study, a novel
      method of surface modification of nanoparticles was first used to modify a
      fluorescent monomer on the surfaces of magnetic nanoparticles directly. This was
      achieved via iron(III)-mediated atom-transfer radical polymerization with
      activators generated by electron transfer (AGET ATRP). Fluorescent monomer 9-(4
      vinylbenzyl)-9H-carbazole (VBK) was synthesized and was grafted from magnetic
      nanoparticles (ferroferric oxide) via AGET ATRP using FeCl(3).6H(2)O as the
      catalyst, tris(3,6-dioxaheptyl)amine (TDA-1) as the ligand, and ascorbic acid
      (AsAc) as the reducing agent. The initiator for ATRP was modified on magnetic
      nanoparticles with the reported method: ligand exchange with 3
      aminopropyltriethoxysilane (APTES) and then esterification with 2-bromoisobutyryl
      bromide. After polymerization, a well-defined nanocomposite (Fe(3)O(4)@PVBK) was
      yielded with a magnetic core and a fluorescent shell (PVBK). Subsequently, well
      dispersed bifunctional nanoparticles (Fe(3)O(4)@PVBK-b-P(PEGMA)) in water were
      obtained via consecutive AGET ATRP of hydrophilic monomer poly(ethylene glycol)
      methyl ether methacrylate (PEGMA). The chemical composition of the magnetic
      nanoparticles' surface at different surface modification stages was investigated
      with Fourier transform infrared (FT-IR) spectra. The magnetic and fluorescent
      properties were validated with a vibrating sample magnetometer (VSM) and a
      fluorophotometer. The Fe(3)O(4)@PVBK-b-P(PEGMA) nanoparticles showed an effective
      imaging ability in enhancing the negative contrast in magnetic resonance imaging
      (MRI).

PMID- 21882879
TI  - Potential-dependent adsorption and transfer of poly(diallyldialkylammonium) ions
      at the nitrobenzene|water interface.
AB  - Electrochemically driven adsorption and partition of a series of
      poly(diallyldialkylammonium) ions (PDADAA(+): alkyl = methyl, ethyl, propyl, and
      butyl) at the nitrobenzene (NB)|water (W) interface have been studied using
      voltammetry and electrocapillary measurements. When the phase-boundary potential,
      Deltaphi, that is, the inner potential of the W phase referred to that of the NB
      phase, is negative, poly(diallyldimethylammonium) (PDADMA(+)) shows little
      surface activity. The scanning of Deltaphi in the positive direction induces,
      first, the adsorption of PDADMA(+) at the interface and, then, the desorption of
      adsorbed PDADMA(+) ions into the NB phase, followed by the diffusion-limited
      transfer of PDADMA(+) from W to NB. The elongation of the dialkyl chains gives
      the stronger surface activity of PDADAA(+) even when Deltaphi < 0. The PDADAA(+)
      polyions studied are only slightly more hydrophilic than the corresponding
      monomers. However, the polycationic character of PDADAA(+) renders the
      adsorption, desorption, and ion transfer strongly dependent on Deltaphi and gives
      rise to unusual, M-shaped electrocapillary curves. The interplay of adsorption
      desorption and ion transfer of PDADAA(+) ions induces the electrochemical
      instability of the interface and the emulsion formation on the NB side of the
      interface.

PMID- 21882880
TI  - Temperature-triggered micellization of block copolymers on an ionic liquid
      surface.
AB  - In situ neutron reflectivity was used to study thermally induced structural
      changes of the lamellae-forming polystyrene-block-poly(2-vinylpyridine) (PS-b
      P2VP) block copolymer thin films floating on the surface of an ionic liquid (IL).
      The IL, 1-butyl-3-methylimidazolium trifluoromethanesulfonate, is a nonsolvent
      for PS and a temperature-tunable solvent for P2VP, and, as such, micellization
      can be induced at the air-IL interface by changing the temperature. Transmission
      electron microscopy and scanning force microscopy were used to investigate the
      resultant morphologies of the micellar films. It was found that highly ordered
      nanostructures consisting of spherical micelles with a PS core surrounded by a
      P2VP corona were produced. In addition, bilayer films of PS homopolymer on top of
      a PS-b-P2VP layer also underwent micellization with increasing temperature but
      the micellization was strongly dependent on the thickness of the PS and PS-b-P2VP
      layers.

PMID- 21882882
TI  - Charge delocalization in self-assembled mixed-valence aromatic cation radicals.
AB  - The spontaneous assembly of aromatic cation radicals (D(+*)) with their neutral
      counterpart (D) affords dimer cation radicals (D(2)(+*)). The intermolecular
      dimeric cation radicals are readily characterized by the appearance of an
      intervalence charge-resonance transition in the NIR region of their electronic
      spectra and by ESR spectroscopy. The X-ray crystal structure analysis and DFT
      calculations of a representative dimer cation radical (i.e., the
      octamethylbiphenylene dimer cation radical) have established that a hole (or
      single positive charge) is completely delocalized over both aromatic moieties.
      The energetics and the geometrical considerations for the formation of dimer
      cation radicals is deliberated with the aid of a series of cyclophane-like
      bichromophoric donors with drastically varied interplanar angles between the
      cofacially arranged aryl moieties. X-ray crystallography of a number of mixed
      valence cation radicals derived from monochromophoric benzenoid donors
      established that they generally assemble in 1D stacks in the solid state.
      However, the use of polychromophoric intervalence cation radicals, where a single
      charge is effectively delocalized among all of the chromophores, can lead to
      higher-order assemblies with potential applications in long-range charge
      transport. As a proof of concept, we show that a single charge in the cation
      radical of a triptycene derivative is evenly distributed on all three benzenoid
      rings and this triptycene cation radical forms a 2D electronically coupled
      assembly, as established by X-ray crystallography.

PMID- 21882881
TI  - The influence of long-term copper contaminated agricultural soil at different pH
      levels on microbial communities and springtail transcriptional regulation.
AB  - Copper has long been applied for agricultural practises. Like other metals,
      copper is highly persistent in the environment and biologically active long after
      its use has ceased. Here we present a unique study on the long-term effects (27
      years) of copper and pH on soil microbial communities and on the springtail
      Folsomia candida an important representative of the soil macrofauna, in an
      experiment with a full factorial, random block design. Bacterial communities were
      mostly affected by pH. These effects were prominent in Acidobacteria, while
      Actinobacteria and Gammaroteobacteria communities were affected by original and
      bioavailable copper. Reproduction and survival of the collembolan F. candida was
      not affected by the studied copper concentrations. However, the transcriptomic
      responses to copper reflected a mechanism of copper transport and detoxification,
      while pH exerted effects on nucleotide and protein metabolism and (acute)
      inflammatory response. We conclude that microbial community structure reflected
      the history of copper contamination, while gene expression analysis of F. candida
      is associated with the current level of bioavailable copper. The study is a first
      step in the development of a molecular strategy aiming at a more comprehensive
      assessment of various aspects of soil quality and ecotoxicology.

PMID- 21882883
TI  - Two-photon 3D FIONA of individual quantum dots in an aqueous environment.
AB  - We report the first two-photon (2P) microscopy of individual quantum dots (QDs)
      in an aqueous environment with both widefield and point-scan excitations at
      nanometer accuracy. Thiol-containing reductants suppress QD blinking and enable
      measurement of the 36 nm step size of individual Myosin V motors in vitro. We
      localize QDs with an accuracy of 2-3 nm in all three dimensions by using a 9 * 9
      matrix excitation hologram and an array detector, which also increases the 3D
      scan imaging rate by 80-fold. With this 3D microscopy we validate the LamB
      receptor distribution on E. coli and the endocytosis of EGF-receptors in breast
      cancer cells.

PMID- 21882884
TI  - A novel method using a silicone diffusion membrane for continuous 222Rn
      measurements for the quantification of groundwater discharge to streams and
      rivers.
AB  - 222Rn is a natural radionuclide that is commonly used as tracer to quantify
      groundwater discharge to streams, rivers, lakes, and coastal environments. The
      use of sporadic point measurements provides little information about short- to
      medium-term processes (hours to weeks) at the groundwater-surface water
      interface. Here we present a novel method for high-resolution autonomous, and
      continuous, measurement of 222Rn in rivers and streams using a silicone diffusion
      membrane system coupled to a solid-state radon-in-air detector (RAD7). In this
      system water is pumped through a silicone diffusion tube placed inside an outer
      air circuit tube that is connected to the detector. 222Rn diffuses from the water
      into the air loop, and the 222Rn activity in the air is measured. By optimizing
      the membrane tube length, wall thickness, and water flow rates through the
      membrane, it was possible to quantify radon variations over times scales of about
      3 h. The detection limit for the entire system with 20 min counting was 18 Bq m-3
      at the 3sigma level. Deployment of the system on a small urban stream showed that
      groundwater discharge is dynamic, with changes in 222Rn activity doubling on the
      scale of hours in response to increased stream flow.

PMID- 21882886
TI  - Acetylation of chicken feathers for thermoplastic applications.
AB  - Poultry feathers are renewable resources, inexpensive and abundantly available,
      but have limited applications. Although keratin extracted from feathers has been
      chemically modified, there are no reports on the chemical modification or
      development of thermoplastics from poultry feathers. Acetylation is an
      inexpensive and environmentally friendly approach to make biopolymers
      thermoplastic. Several biopolymers have been acetylated and used to produce
      fibers, films, and extrudates. In this research, chicken feathers were
      acetylated, and the structure and properties of the acetylated feathers were
      studied. Acetylation conditions such as concentration of chemicals and catalyst
      and time and temperature of acetylation were optimized. Acetylation of feathers
      was confirmed using Fourier transform infrared (FTIR) and pyrolysis-gas
      chromatography-mass spectrometry (P-GC-MS). The acetylated feathers were analyzed
      using thermogravimetric analysis (TGA) and differential scanning calorimetry
      (DSC) to understand their thermal behavior. Acetylated feathers were
      thermoplastic and could be compression molded to form transparent films despite
      the relatively low percentage of acetyl content.

PMID- 21882885
TI  - Effects of a protecting osmolyte on the ion atmosphere surrounding DNA duplexes.
AB  - Osmolytes are small, chemically diverse, organic solutes that function as an
      essential component of cellular stress response. Protecting osmolytes enhance
      protein stability via preferential exclusion, and nonprotecting osmolytes, such
      as urea, destabilize protein structures. Although much is known about osmolyte
      effects on proteins, less is understood about osmolyte effects on nucleic acids
      and their counterion atmospheres. Nonprotecting osmolytes destabilize nucleic
      acid structures, but effects of protecting osmolytes depend on numerous factors
      including the type of nucleic acid and the complexity of the functional fold. To
      begin quantifying protecting osmolyte effects on nucleic acid interactions, we
      used small-angle X-ray scattering (SAXS) techniques to monitor DNA duplexes in
      the presence of sucrose. This protecting osmolyte is a commonly used contrast
      matching agent in SAXS studies of protein-nucleic acid complexes; thus, it is
      important to characterize interaction changes induced by sucrose. Measurements of
      interactions between duplexes showed no dependence on the presence of up to 30%
      sucrose, except under high Mg(2+) conditions where stacking interactions were
      disfavored. The number of excess ions associated with DNA duplexes, reported by
      anomalous small-angle X-ray scattering (ASAXS) experiments, was sucrose
      independent. Although protecting osmolytes can destabilize secondary structures,
      our results suggest that ion atmospheres of individual duplexes remain
      unperturbed by sucrose.

PMID- 21882887
TI  - pH-induced intramolecular folding dynamics of i-motif DNA.
AB  - Using the combination of fluorescence resonance energy transfer (FRET) and
      fluorescence correlation spectroscopy (FCS) technique, we investigate the
      mechanism and dynamics of the pH-induced conformational change of i-motif DNA in
      the bulk phases and at the single-molecule level. Despite numerous studies on i
      motif that is formed from cytosine (C)-rich strand at slightly acidic pH, its
      detailed conformational dynamics have been rarely reported. Using the FRET
      technique to provide valuable information on the structure of biomolecules such
      as a protein and DNA, we clearly show that the partially folded species as well
      as the single-stranded structure coexist at neutral pH, supporting that the
      partially folded species may exist substantially in vivo and play an important
      role in a process of gene expression. By measuring the FCS curves of i-motif, we
      observed the gradual decrease of the diffusion coefficient of i-motif with
      increasing pH. The quantitative analysis of FCS curves supports that the gradual
      decrease of diffusion coefficient (D) associated with the conformational change
      of i-motif is not only due to the change in the intermolecular interaction
      between i-motif and solvent accompanied by the increase of pH but also due to the
      change of the shape of DNA. Furthermore, FCS analysis showed that the intrachain
      contact formation and dissociation for i-motif are 5-10 times faster than that
      for the open form. The fast dynamics of i-motif with a compact tetraplex is due
      to the intrinsic conformational changes at the fluorescent site including the
      motion of alkyl chain connecting the dye to DNA, whereas the slow intrachain
      contact formation observed from the open form is due to the DNA motion
      corresponding to an early stage interaction in the folding process of the
      unstructured open form.

PMID- 21882888
TI  - Effect of buckwheat extract on the antioxidant activity of lipid in mouse brain
      and its structural change during in vitro human digestion.
AB  - This study was conducted to investigate the effects of buckwheat ( Fagopyrum
      esculentum  Moench cv. Yangjul No. 2) extract on the antioxidant activity of
      lipids in mouse brain and the structural change during in vitro human digestion.
      Buckwheat was collected from a wild farm and extracted with water. The buckwheat
      extracts were then passed through an in vitro human digestion model that
      simulated the composition of the mouth, stomach, and small intestine juice. The
      results confirmed that the main phenolics of buckwheat extract were rutin,
      quercitrin, and quercetin. The rutin content increased with digestion of the
      buckwheat (from 48.82 to 96.34 MUg/g) and rutin standard samples (from 92.76 to
      556.56 MUg/g). Antioxidant activity was more strongly influenced by in vitro
      human digestion of both buckwheat and rutin standard. After digestion by the
      small intestine, the antioxidant activity values were dramatically increased
      (from 5.06 to 87.82%), whereas the antioxidant activity was not influenced by
      digestion in the stomach for both buckwheat extract and rutin standard.
      Inhibition of lipid oxidation of buckwheat in mouse brain lipids increased after
      digestion in the stomach for both buckwheat extract and the rutin standard. The
      major finding of this study was that in vitro human digestion may be an important
      modulator of the antioxidant capacity of buckwheat and that this may be because
      in vitro human digestion increased the antioxidative activity via an increase in
      antioxidants such as rutin and quercetin.

PMID- 21882889
TI  - Use of mid-upper arm circumference in determining undernutrition and illness in
      rural adult Oraon men of Gumla District, Jharkhand, India.
AB  - INTRODUCTION: Body mass index (BMI) is widely accepted as one of the best
      indicators of nutritional status in adults. Mid-upper arm circumference (MUAC) is
      another anthropometric measure that has also been used to evaluate adult
      nutritional status. The objective of this study was to evaluate the use of MUAC
      as a simpler and reliable alternative to BMI. A suitable cut-off value was also
      proposed for identification of chronic energy deficiency (CED) in relation to
      self-reported illness among the adult Oraon males of Jharkhand state in India.
      METHODS: The study was based on a cross-sectional survey involving 205 rural
      adult men belonging to the Oraon tribal group of Jharkand State in India. Height
      and weight were measured for each participant. The BMI was calculated as kg/m2.
      The internationally accepted cut-off points of BMI and MUAC were utilised to
      determine nutritional status. An episode of illness was recorded for each subject
      if any working day was lost. Receiver operating characteristic curve analyses
      were undertaken to discover the most suitable values of MUAC both for CED and
      illness. RESULTS: The MUAC values of 243 and 239 mm were identified as the best
      cut offs to identify CED (BMI<18.5) and illness, respectively. There were marked
      increases in both CED and illness prevalence rates at a MUAC level lower than 240
      mm. Therefore, a MUAC value of close to 240 mm seemed appropriate as a simple and
      efficient cut-off point for the determination of undernutrition and higher rates
      of illness and loss of working days in adult Oraon males. CONCLUSION: Because
      MUAC is a much simpler measure than BMI, the use of MUAC 240 mm as a cut-off
      point is predicted to have considerable public health implications, especially
      with respect to primary health care related to CED and morbidity.

PMID- 21882895
TI  - Neurite outgrowth in fibrin gels is regulated by substrate stiffness.
AB  - Fibrin is a promising matrix for use in promoting nerve repair given its natural
      occurrence in peripheral nerve injuries, and the biophysical properties of this
      matrix can be regulated to modulate tissue regeneration. In this study, we
      examined the effect of physical and mechanical properties of fibrin gels on
      dorsal root ganglia (DRG) neurite extension. Increases in fibrinogen
      concentration increased the number of fibrin strands, resulting in decreased pore
      size and increased stiffness. Neurite extension was reduced when DRG explants
      were cultured within fibrin gels of increasing fibrinogen concentrations (from
      9.5 to 141 mg/mL). The addition of NaCl also increased the number of fibrin
      strands, reducing fiber diameter and porosity, while increasing mechanical
      strength, and reductions in neurite extension correlated with increases in NaCl
      content. We determined that neurite extension within fibrin gels is dependent on
      fibrinolysis and is mediated by the secretion of serine proteases and matrix
      metalloproteinases by entrapped DRGs, as confirmed by culturing cells in the
      presence of inhibitors against these enzymes and real-time-polymerase chain
      reaction. Taken together, the results of this study provide new insight into the
      effect of fibrin gel biophysical properties on neurite extension and suggest new
      opportunities to improve the efficacy of these materials when used as nerve
      guidance conduits.

PMID- 21882896
TI  - Enzymatic crosslinking and degradation of gelatin as a switch for bone
      morphogenetic protein-2 activity.
AB  - Current therapies for tissue regeneration rely on the presence or direct delivery
      of growth factors to sites of repair. Bone morphogenetic protein-2 (BMP-2),
      combined with a carrier (usually collagen), is clinically proven to induce new
      bone formation during spinal fusion and nonunion repair. However, due to BMP-2's
      short half-life and its diffusive properties, orders of magnitude above
      physiological levels are required to ensure effectiveness. In addition, a high
      dose of this multifunctional growth factor is known to induce adverse effects in
      patients. To circumvent these challenges, we proposed and tested a new approach
      for BMP-2 delivery, by controlling BMP activity via carrier binding and localized
      proteolysis. BMP-2 was covalently bound to gelatin through site-specific
      enzymatic crosslinking using a microbial transglutaminase. Binding of BMP-2 to
      gelatin can completely switch off BMP-2 activity, as evidenced by loss of its
      transdifferentiating ability toward C2C12 promyoblasts. When gelatin sequestered
      BMP-2 is incubated with either microbial collagenase or tissue-derived matrix
      metalloproteinases, BMP-2 activity is fully restored. The activity of released
      BMP-2 correlates with the protease activity in a dose- and time-dependent manner.
      This observation suggests a novel way of delivering BMP-2 and controlling its
      activity. This improved delivery method, which relies on a physiological
      feedback, should enhance the known potential of this and other growth factors for
      tissue repair and regeneration.

PMID- 21882897
TI  - The detection of food soils on stainless steel using energy dispersive X-ray and
      Fourier transform infrared spectroscopy.
AB  - Organic soiling is a major issue in the food processing industries, causing a
      range of biofouling and microbiological problems. Energy dispersive X-ray (EDX)
      and Fourier transform infra red spectroscopy (FT-IR) were used to quantify and
      determine the biochemical groups of food soils on stainless steel surfaces. EDX
      quantified organic material on surfaces where oily based residues predominated,
      but was limited in its usefulness since other food soils were difficult to
      detect. FT-IR provided spectral 'fingerprints' for each of the soils tested. Key
      soiling components were associated with specific peaks, viz. oils at 3025 cm(-1)
      3011 cm(-1), proteins at 1698 cm(-1)-1636 cm(-1) and carbohydrates at 1658 cm(-1)
      1596 cm(-1), 783 cm(-1)-742 cm(-1). High concentrations of some soils (10%) were
      needed for detection by both EDX and FT-IR. The two techniques may be of use for
      quantifying and identifying specific recalcitrant soils on surfaces to improve
      cleaning and hygiene regimes.

PMID- 21882899
TI  - Engineered antifouling microtopographies: kinetic analysis of the attachment of
      zoospores of the green alga Ulva to silicone elastomers.
AB  - Microtopography has been demonstrated as an effective deterrent to biofouling.
      The majority of published studies are fixed-time assays that raise questions
      regarding the kinetics of the attachment process. This study investigated the
      time-dependent attachment density of zoospores of Ulva, in a laboratory assay, on
      a micropatterned and smooth silicone elastomer. The attachment density of
      zoospores was reduced on average 70-80% by the microtopography relative to smooth
      surfaces over a 4 h exposure. Mapping the zoospore locations on the topography
      revealed that they settled preferentially in specific, recessed areas of the
      pattern. The kinetic data fit, with high correlation (r(2) > 0.9), models
      commonly used to describe the adhesion of bacteria to surfaces. The grouping of
      spores on the microtopography indicated that the pattern inhibited the ability of
      attached spores to recruit neighbors. This study demonstrates that the
      antifouling mechanism of topographies may involve disruption of the cooperative
      effects exhibited by fouling organisms such as Ulva.

PMID- 21882900
TI  - MCF-7 cells as a three-dimensional model for the study of human breast cancer.
AB  - The increasing use of three-dimensional (3D) cell culture is because it
      reproduces in vitro results similar to in vivo results. Multicellular tumor
      spheroids generated in vitro exhibit important characteristics of avascular
      tumors, mainly with respect to tumor physiology and microenvironment. The
      interaction among cells in a tridimensional culture environment enhances cell
      differentiation and leads to luminal formation in some breast-derived cell
      cultures. The present work describes a method that permits luminal formation in
      breast adenocarcinoma cell (MCF-7)-derived spheroids in a 3D environment. In the
      proposed model, several relevant parameters, such as cell survival, apoptosis,
      autophagy, and E-cadherin expression, were analyzed to understand the
      organization of MCF-7 cells during different culture phases, including luminal
      and bud formation.

PMID- 21882898
TI  - Inhibition of marine biofouling by bacterial quorum sensing inhibitors.
AB  - Seventy eight natural products from chemical libraries containing compounds from
      marine organisms (sponges, algae, fungi, tunicates and cyanobacteria) and
      terrestrial plants, were screened for the inhibition of bacterial quorum sensing
      (QS) using a reporter strain Chromobacterium violaceum CV017. About half of the
      natural products did not show any QS inhibition. Twenty four percent of the
      tested compounds inhibited QS of the reporter without causing toxicity. The QS
      inhibitory activities of the most potent and abundant compounds were further
      investigated using the LuxR-based reporter E. coli pSB401 and the LasR-based
      reporter E. coli pSB1075. Midpacamide and tenuazonic acid were toxic to the
      tested reporters. QS-dependent luminescence of the LasR-based reporter, which is
      normally induced by N-3-oxo-dodecanoyl-L-homoserine lactone, was reduced by
      demethoxy encecalin and hymenialdisin at concentrations >6.6 MUM and 15 MUM,
      respectively. Hymenialdisin, demethoxy encecalin, microcolins A and B and kojic
      acid inhibited responses of the LuxR-based reporter induced by N-3-oxo-hexanoyl-L
      homoserine lactone at concentrations >0.2 MUM, 2.2 MUM, 1.5 MUM, 15 MUM and 36
      MUM, respectively. The ability to prevent microfouling by one of the compounds
      screened in this study (kojic acid; final concentrations 330 MUM and 1 mM) was
      tested in a controlled mesocosm experiment. Kojic acid inhibited formation of
      microbial communities on glass slides, decreasing the densities of bacteria and
      diatoms in comparison with the control lacking kojic acid. The study suggests
      that natural products with QS inhibitory properties can be used for controlling
      biofouling communities.

PMID- 21882901
TI  - Is pacemaker deactivation at the end of life unique? A case study and ethical
      analysis.
AB  - Although there has been considerable controversy regarding the deactivation of
      pacemakers near the end of life, clinicians can expect to face more requests for
      pacemaker withdrawal as the number of implants grows. Despite a clear ethical and
      legal precedent, these requests may elicit significant psychological and moral
      distress on the part of the clinical team. We illustrate some of the difficulties
      clinicians may face by describing the case of a patient with end-stage heart
      failure who asked to have her pacemaker turned off near the end of life. We
      discuss the challenges in determining pacemaker dependency, differing attitudes
      toward deactivating pacemakers versus other cardiac devices, and how the issues
      of perceived burden and timing of death may contribute to a clinician's sense of
      moral distress.

PMID- 21882902
TI  - Metformin as a geroprotector.
AB  - Abstract   Geroprotectors are drugs that decrease the rate of aging and therefore
      extend life span. Metformin has been described as a geroprotector, and several
      studies have shown that metformin can slow down the rate of aging. The mechanisms
      behind the geroprotective effect of metformin are less established. The goal of
      this review is to investigate the evidence for the geroprotective effect of
      metformin and to describe the possible mechanisms behind it.

PMID- 21882903
TI  - Inferring mechanisms of compensation from E-MAP and SGA data using local search
      algorithms for max cut.
AB  - A new method based on a mathematically natural local search framework for max cut
      is developed to uncover functionally coherent module and BPM motifs in high
      throughput genetic interaction data. Unlike previous methods, which also consider
      physical protein-protein interaction data, our method utilizes genetic
      interaction data only; this becomes increasingly important as high-throughput
      genetic interaction data is becoming available in settings where less is known
      about physical interaction data. We compare modules and BPMs obtained to previous
      methods and across different datasets. Despite needing no physical interaction
      information, the BPMs produced by our method are competitive with previous
      methods. Biological findings include a suggested global role for the prefoldin
      complex and a SWR subcomplex in pathway buffering in the budding yeast
      interactome.

PMID- 21882904
TI  - Pain, health related quality of life and healthcare resource utilization in
      Spain.
AB  - OBJECTIVES: The aim of this paper is to consider the relationship between the
      experience of pain, health related quality of life (HRQoL) and healthcare
      resource utilization in Spain. METHODS: The analysis contrasts the contribution
      of pain severity and frequency of pain reported against respondents reporting no
      pain in the previous month. Data are from the 2010 National Health and Wellness
      Survey (NHWS) for Spain. Single equation generalized linear regression models are
      used to evaluate the association of pain with the physical and mental component
      scores of the SF-12 questionnaire as well as health utilities generated from the
      SF-6D. In addition, the role of pain is assessed in its association with self
      reported healthcare provider visits, emergency room visits and hospitalizations
      in the previous 6 months. RESULTS: The results indicate that the experience of
      pain, notably severe and frequent pain, is substantial and is significantly
      associated with the SF-12 physical component scores, health utilities and all
      aspects of healthcare resource utilization, which far outweighs the role of
      demographic and socioeconomic variables, health risk factors (in particular body
      mass index) and the presence of comorbidities. In the case of severe daily pain,
      the marginal contribution of the SF-12 physical component score is a deficit of 
      17.86 compared to those reporting no pain (population average score 46.49), while
      persons who are morbidly obese report a deficit of only -6.63 compared to those
      who are normal weight. The corresponding association with health utilities is
      equally dramatic with a severe daily pain deficit of -0.186 compared to those
      reporting no pain (average population utility 0.71). The impact of pain on
      healthcare resource utilization is marked. Severe daily pain increases
      traditional provider visits by 208.8%, emergency room visits by 373.0% and
      hospitalizations by 348.5%. LIMITATIONS: As an internet-based survey there is the
      possibility of bias towards those with internet access, although telephone
      sampling is used to supplement responses. Respondents are asked to describe their
      experience of pain; there is no independent check on the accuracy of responses.
      Finally, while certain acute pain categories are omitted, the study focuses on
      pain in the last month and not on pain chronicity. CONCLUSIONS: The societal
      burden of severe and frequent pain in Spain is substantial. Although not reported
      on before, at a national level, the deficit impact of the experience of pain far
      outweighs the contribution of more traditional explanations of HRQoL deficits as
      well as being the primary factor associated with increased provider visits,
      emergency room visits and hospitalizations.

PMID- 21882906
TI  - Familial Chiari malformation: case series.
AB  - Chiari malformations (Types I-IV) are abnormalities of the posterior fossa that
      affect the cerebellum, brainstem, and the spinal cord with prevalence rates of
      0.1%-0.5%. Case reports of familial aggregation of Chiari malformation, twin
      studies, cosegregation of Chiari malformation with known genetic conditions, and
      recent gene and genome-wide association studies provide strong evidence of the
      genetic underpinnings of familial Chiari malformation. The authors report on a
      series of 3 family pairs with Chiari malformation Type I: 2 mother-daughter pairs
      and 1 father-daughter pair. The specific genetic causes of familial Chiari
      malformation have yet to be fully elucidated. The authors review the literature
      and discuss several candidate genes. Recent advances in the understanding of the
      genetic influences and pathogenesis of familial Chiari malformation are expected
      to improve management of affected patients and monitoring of at-risk family
      members.

PMID- 21882907
TI  - Chiari malformation associated with craniosynostosis.
AB  - OBJECT: Chiari malformation (CM) Type I is frequently associated with
      craniosynostosis. Optimal management of CM in patients with craniosynostosis is
      not well-established. The goal of this study was to report on a series of
      pediatric patients with both craniosynostosis and CM and discuss their
      management. METHODS: The authors searched the medical records of 383 consecutive
      patients treated for craniosynostosis at a single institution over a 15-year
      period to identify those with CM. They recorded demographic data as well as
      surgical treatment and outcomes for these patients. When MR imaging was
      performed, cerebellar tonsillar descent was recorded and any other associated
      findings, such as hydrocephalus or spinal syringes, were noted. RESULTS: A total
      of 29 patients with both CM and craniosynostosis were identified. Of these cases,
      28% had associated occipital venous abnormalities, 45% were syndromic, and 52%
      also had hydrocephalus. Chiari malformation was more likely to be present in
      those patients with isolated lambdoid synostosis (55%), multisuture synostosis
      (35%), and pansynostosis (80%), compared with patients with coronal synostosis
      (6%) or sagittal synostosis (3%). All patients underwent surgical repair of
      craniosynostosis: 16 had craniosynostosis repair as well as CM decompression, and
      13 patients did not undergo CM decompression. Of the 7 patients in whom
      craniosynostosis repair alone was performed, 5 had decreased tonsillar ectopia
      postoperatively and 5 had improved CSF flow studies postoperatively. Both
      patients with a spinal syrinx had imaging-documented syrinx regression after
      craniosynostosis repair. In 12 patients in whom CM was diagnosed after primary
      craniosynostosis repair, 5 had multiple cranial vault expansions and evidence of
      elevated intracranial pressure. In 5 cases, de novo CM development was documented
      following craniosynostosis repair at a mean of 3.5 years after surgery.
      CONCLUSIONS: Chiari malformation is frequently seen in patients with both multi-
      and single-suture lambdoid craniosynostosis. Chiari malformation, and even a
      spinal cord syrinx, will occasionally resolve following craniofacial repair. De
      novo development of CM after craniosynostosis repair is not unusual.

PMID- 21882908
TI  - Associated disorders of Chiari Type I malformations: a review.
AB  - A single pathophysiological mechanism of Chiari Type I malformations (CM-I) has
      been a topic of debate. To help better understand CM-I, the authors review
      disorders known to be associated with CM-I. The primary methodology found among
      most of them is deformation of the posterior cranial fossa, usually with
      subsequent decrease in volume. Other mechanisms exist as well, which can be
      categorized as either congenital or acquired. In understanding the relationship
      of such disorders with CM-I, we may gain further insight into the process by
      which cerebellar tonsillar herniation occurs. Some of these pathologies appear to
      be true associations, but many appear to be spurious.

PMID- 21882909
TI  - Volumetric analysis of syringomyelia following hindbrain decompression for Chiari
      malformation Type I: syringomyelia resolution follows exponential kinetics.
AB  - OBJECT: Resolution of syringomyelia is common following hindbrain decompression
      for Chiari malformation, yet little is known about the kinetics governing this
      process. The authors sought to establish the volumetric rate of syringomyelia
      resolution. METHODS: A retrospective cohort of patients undergoing hindbrain
      decompression for a Chiari malformation Type I with preoperative cervical or
      thoracic syringomyelia was identified. Patients were included in the study if
      they had at least 3 neuroimaging studies that detailed the entirety of their
      preoperative syringomyelia over a minimum of 6 months postoperatively. The
      authors reconstructed the MR images in 3 dimensions and calculated the volume of
      the syringomyelia. They plotted the syringomyelia volume over time and
      constructed regression models using the method of least squares. The Akaike
      information criterion and Bayesian information criterion were used to calculate
      the relative goodness of fit. The coefficients of determination R(2) (unadjusted
      and adjusted) were calculated to describe the proportion of variability in each
      individual data set accounted for by the statistical model. RESULTS: Two patients
      were identified as meeting inclusion criteria. Plots of the least-squares best
      fit were identified as 4.01459e(-0.0180804)(x) and 13.2556e(-0.00615859)(x).
      Decay of the syringomyelia followed an exponential model in both patients (R(2) =
      0.989582 and 0.948864). CONCLUSIONS: Three-dimensional analysis of syringomyelia
      resolution over time enables the kinetics to be estimated. This technique is yet
      to be validated in a large cohort. Because syringomyelia is the final common
      pathway for a number of different pathological processes, it is possible that
      this exponential only applies to syringomyelia related to treatment of Chiari
      malformation Type I.

PMID- 21882910
TI  - Standard and cardiac-gated phase-contrast magnetic resonance imaging in the
      clinical course of patients with Chiari malformation Type I.
AB  - OBJECT: The causal treatment of Chiari malformation Type I (CM-I) consists of
      removing the obstruction of CSF flow at the level of the foramen magnum.
      Cerebrospinal fluid flow can be visualized using dynamic phase-contrast MR
      imaging. Because there is only a paucity of studies evaluating CSF dynamics in
      the region of the spinal canal on the basis of preoperative and postoperative
      measurements, the authors investigated the clinical usefulness of cardiacgated
      phase-contrast MR imaging in patients with CM-I. METHODS: Ninety patients with CM
      I underwent preoperative MR imaging of CSF pulsation. Syringomyelia was present
      in 59 patients and absent in 31 patients. Phase-contrast MR imaging of the entire
      CNS was used to investigate 22 patients with CM-I before surgery and after a mean
      postoperative period of 12 months (median 12 months, range 3-33 months). In
      addition to the dynamic studies, absolute flow velocities, the extension of the
      syrinx, and tonsillar descent were also measured. RESULTS: The changes in
      pulsation were highly significant in the region of the (enlarged) cistern (p =
      0.0005). Maximum and minimum velocities (the pulsation amplitude) increased
      considerably in the region where the syrinx was largest in diameter. The changes
      of pulsation in these patients were significant in the subarachnoid space in all
      spinal segments but not in the syrinx itself and in the central canal.
      CONCLUSIONS: The demonstration of CSF flow pulsation can contribute to
      assessments of surgical outcomes. The results presented here, however, raise
      doubts about current theories on the pathogenesis of syringomyelia.

PMID- 21882911
TI  - Chiari malformation.

PMID- 21882912
TI  - Developmental anatomy of the atlas and axis in childhood by computed tomography.
AB  - OBJECT: The CT modality plays a central role in the diagnosis of cervical spine
      fractures. In childhood, radiolucent synchondroses between ossification centers
      can resemble fractures, and they can be the sites of fractures as well.
      Recognition of cervical spine fractures in children requires familiarity with
      normal developmental anatomy and common variants as they appear on CT scans.
      METHODS: A convenience sample of 932 CT scans of the cervical spine accessible on
      the picture archiving and communications system (known as PACS) at a single
      children's hospital was examined. Scans were excluded from further analysis if
      they did not include the atlantoaxial region or were otherwise technically
      unsatisfactory; if the patient carried the diagnosis of a skeletal dysplasia; or
      if there were developmental lesions noted at other levels of the spine. No more
      than 1 scan per patient was analyzed. Synchondroses were graded as radiolucent,
      not totally radiolucent but still visible, or no longer visible. Their locations
      and symmetries were noted. The presence or absence of the tubercles of the
      transverse ligament was noted as well. RESULTS: After exclusions, 841 studies of
      the atlas and 835 studies of the axis were analyzed. The 3 common ossification
      centers of the atlas arose in the paired neural arches and the anterior arch, but
      in as many as 20% of cases the anterior arch developed from paired symmetrical
      ossification centers. The 5 common ossification centers of the axis arose in the
      paired neural arches, in the basal center, in the dentate center (from which most
      of the dentate process develops), and in the very apex of the dentate process.
      The appearance of each synchondrosis was noted at sequential ages. The tubercles
      for the transverse ligament generally did not appear until the ossification of
      the synchondroses of the atlas was far advanced. Anomalies of the atlas included
      anterior and posterior spina bifida, absence of sectors of the posterior arch,
      and anomalous ossification centers and synchondroses. Anomalies of the axis were
      much less common. What appeared possibly to be chronic, incompletely healed
      fractures of the atlas were discovered on review for this analysis in 6 cases. No
      fractures of the axis were discovered. CONCLUSIONS: There is substantial
      variation in the time course and pattern of development of the atlas, and
      anomalies are common. Some fractures of the atlas may escape recognition without
      manifest sequelae. Variation in the time course of the development of the axis is
      notable as well, but anomalies seem much less common.

PMID- 21882913
TI  - Repeat surgery for residual ependymoma.

PMID- 21882914
TI  - Second-look surgery for ependymoma: the Italian experience.
AB  - OBJECT: Complete ependymoma resection ensures a better prognosis for children
      with this tumor, but the complete excision of infratentorial ependymomas involves
      serious risks. Second-look surgery for tumor remnants may be less harmful and
      enable complete removal. There is a potential, although still unclear, role for
      neoadjuvant chemotherapy in preparation for further surgery. METHODS: Since 1994,
      the authors have adopted two successive protocols for intracranial ependymoma,
      both including a phase of adjuvant chemotherapy for children with surgical tumor
      remnants with a plan for potential second-look surgery before radiotherapy.
      RESULTS: In the first protocol, 9 of 63 children underwent further surgery, and 6
      became tumor free with no additional sequelae. Their prognosis for progression
      free survival and freedom from local relapse was comparable to that of children
      who were operated on only once. In the second protocol, efforts were made to
      achieve complete resection and 29 of 110 patients underwent reoperations: 9 after
      the first surgery, 17 after chemotherapy, and 3 soon after radiotherapy. Fourteen
      of the 29 patients became tumor free, 1 of them with worsening neurological
      symptoms. The outcome of the 66 patients who became tumor free after 1 operation
      was compared with that of the 14 who became tumor free after reoperation. The 3
      year progression-free survival of the 66 patients compared with the 14 other
      patients was 71.4% +/- 6.9% and 90% +/- 9.5%, respectively; the 3-year freedom
      from local relapse was 84.7% +/- 5.9% and 90% +/- 9.5%, respectively; and the 3
      year overall survival was 85.9% +/- 5.4% and 87.5% +/- 11.7%, respectively.
      CONCLUSIONS: Second-look surgery proved feasible with no major morbidity, and
      results improved with time. Local tumor control was comparable in patients
      undergoing 1 or more resections.

PMID- 21882915
TI  - Resection of infantile brain tumors after neoadjuvant chemotherapy: the St. Jude
      experience.
AB  - OBJECT: Brain tumors in infants are often large, high grade, and vascular, making
      complete resection difficult and placing children at risk for neurological
      complications and excessive blood loss. Neoadjuvant chemotherapy may reduce tumor
      vascularity and volume, which can facilitate resection. The authors evaluated how
      an ongoing institutional prospective chemotherapy trial would affect patients who
      did not have a gross-total resection (GTR) immediately and who therefore required
      further surgical intervention to achieve definitive tumor resection. METHODS:
      Thirteen infants (4 girls and 9 boys) who were enrolled in an institutional
      protocol in which they were treated with multiagent chemotherapy (methotrexate,
      vincristine, cisplatin, and cyclophosphamide with vinblastine for high-risk
      patients) subsequently underwent second-look surgery. The primary outcome was
      extent of resection achieved in postchemotherapy surgery. Secondary outcomes
      included intraoperative blood loss, radiographic response to the chemotherapy,
      complications during chemotherapy, and survival. RESULTS: Three infants underwent
      biopsy, 9 underwent subtotal resection, and 1 patient did not undergo surgery
      prior to chemotherapy. On subsequent second-look surgery, 11 of 13 patients had a
      GTR, 1 had a near-total resection, and 1 had a subtotal resection. In each case,
      a marked reduction in tumor vascularity was observed intraoperatively. The
      average blood loss was 19% of estimated blood volume, and 6 (46%) of 13 patients
      required a blood transfusion. Radiographically, chemotherapy induced a reduction
      in tumor volume in 9 (69%) of 13 patients. Emergency surgery was required in 2
      patients during chemotherapy, 1 for intratumoral hemorrhage and 1 for worsening
      peritumoral edema. The average follow-up period for this cohort was 16.5 months,
      and at last follow-up, 4 patients (31%) had died, 1 patient had progressive
      metastatic spinal disease, and the rest had either no evidence of disease or
      stable disease. CONCLUSIONS: A GTR of pediatric brain tumors is one of the most
      important predictors of outcome. The application of the authors' neoadjuvant
      induction chemotherapy protocol in a variety of tumor types resulted in
      devascularization of all tumors and volume regression in the majority, and
      subsequently facilitated resection, with acceptable intraoperative blood loss.
      Intracranial complications may occur during chemotherapy, ranging from incidental
      and asymptomatic to life threatening, necessitating close monitoring of these
      children.

PMID- 21882916
TI  - Pooling data on antibiotic-impregnated shunts.

PMID- 21882917
TI  - Cerebrospinal shunt infection in patients receiving antibiotic-impregnated versus
      standard shunts.
AB  - OBJECT: Cerebrospinal fluid shunt infections are associated with significant
      morbidity and mortality in the treatment of adult and pediatric hydrocephalus.
      Antibiotic-impregnated shunt (AIS) catheters have been used with the aim of
      reducing shunt infection. While many studies have demonstrated a reduction in
      shunt infection with AIS, this reported efficacy has varied within the
      literature. METHODS: The authors performed a systematic literature review to
      identify all published articles comparing the incidence of CSF shunt infection in
      AIS versus non-AIS catheters. The incidence of infection for AIS versus non-AIS
      catheters was calculated using the Mantel-Haenszel common odds ratio, and
      baseline demographics were compared between AIS and non-AIS cohorts. RESULTS:
      Twelve AIS versus non-AIS cohort comparisons were identified in the literature (5
      pediatric hydrocephalus, 3 adult hydrocephalus, and 4 mixed populations). In a
      total of 5613 reported shunt procedures (2664 AISs vs 2949 non-AISs), AISs were
      associated with a reduction in shunt infection (3.3% vs 7.2%; OR 0.439, p <
      0.0001). In 787 shunt procedures for adult hydrocephalus (427 AIS vs 360 non
      AIS), AISs were associated with reduction in shunt infection (0.9% vs 5.8%; OR
      0.153, p < 0.0001). In 1649 shunt procedures for pediatric hydrocephalus (854 AIS
      vs 795 non-AIS), AISs were associated with reduction in shunt infection (5.0% vs
      11.2%; OR 0.421, p < 0.0001). CONCLUSIONS: The authors' systematic review of the
      literature demonstrates that AIS catheters are associated with a significant
      reduction over non-AIS catheters in the reported incidence of CSF shunt infection
      in adult and pediatric populations. The AIS catheters do not appear to be
      associated with an increased incidence of antibiotic-resistant microorganisms.
      Prospective, randomized trials are needed to firmly assess and confirm this
      apparent difference in infection incidence.

PMID- 21882918
TI  - Invasive monitoring.

PMID- 21882919
TI  - Outcome of no resection after long-term subdural electroencephalography
      evaluation in children with epilepsy.
AB  - OBJECT: The aim of this study was to identify the reasons for and predictors of
      no resection of the epileptogenic zone in children with epilepsy who had
      undergone long-term invasive subdural grid electroencephalography (SDG-EEG)
      evaluation. METHODS: The authors retrospectively reviewed the consecutive medical
      records of children (< 19 years of age) who had undergone SDG-EEG evaluation over
      a 7-year period (1997-2004). To determine the predictors of no resection, the
      authors obtained the clinical characteristics and imaging and EEG findings of
      children who had no resection after long-term invasive SDG-EEG evaluation and
      compared these data with those in a group of children who did undergo resection.
      They describe the indications for SDG-EEG evaluation and the reasons for no
      resection in these patients. RESULTS: Of 66 children who underwent SDG-EEG
      evaluation, 9 (13.6%) did not undergo subsequent resection (no-resection group; 6
      males). Of these 9 patients, 6 (66.7%) had normal neurological examinations and 5
      (55.6%) had normal findings on brain MR imaging. Scalp video EEG localized
      epilepsy to the left hemisphere in 6 of the 9 patients and to the right
      hemisphere in 2; it was nonlocalizable in 1 of the 9 patients. Indications for
      SDG-EEG in the no-resection group were ictal onset zone (IOZ) localization (9 of
      9 patients), motor cortex localization (5 of 9 patients), and language area
      localization (4 of 9 patients). Reasons for no resection after SDG-EEG evaluation
      were the lack of a well-defined IOZ in 5 of 9 patients (4 multifocal IOZs and 1
      nonlocalizable IOZ) and anticipated new permanent postoperative neurological
      deficits in 7 of 9 patients (3 motor, 2 language, and 2 motor and language
      deficits). Comparison with the resection group (57 patients) demonstrated that
      postictal Todd paralysis in the dominant hand was the only variable seen more
      commonly (chi(2) = 4.781, p = 0.029) in the no-resection group (2 [22.2%] of 9 vs
      2 [3.5%] of 57 patients). The no-resection group had a larger number of SDG
      electrode contacts (mean 126. 5 +/- 26.98) as compared with the resection group
      (100.56 +/- 25.52; p = 0.010). There were no significant differences in the
      demographic data, seizure characteristics, scalp and invasive EEG findings, and
      imaging variables between the resection and no-resection groups. CONCLUSIONS:
      Children who did not undergo resection of the epileptogenic zone after SDG-EEG
      evaluation were likely to have normal neurological examinations without
      preexisting neurological deficits, a high probability of a new unacceptable
      permanent neurological deficit following resection, or multifocal or
      nonlocalizable IOZs. In comparison with the group that underwent resection after
      SDG-EEG, a history of Todd paralysis in the dominant hand and arm was the only
      predictor of no resection following SDG-EEG evaluation. Data in this study will
      help to better select pediatric patients for SDG-EEG and to counsel families
      prior to epilepsy surgery.

PMID- 21882920
TI  - Combined intraoperative magnetic resonance imaging and navigated neuroendoscopy
      in children with multicompartmental hydrocephalus and complex cysts: a
      feasibility study.
AB  - OBJECT: The rationale for using endoscopy to treat complex cysts and
      multiloculated hydrocephalus is to combine several CSF compartments into a
      minimum number, establish a connection to functioning CSF compartments (that is,
      ventricles), and decrease shunt dependency. The aim is to decrease the number of
      proximal shunt catheters, the number of shunt revisions, and in selected cases
      even to avoid a shunt. In cases of distorted anatomy and multiloculated cysts,
      endoscopy may be problematic because of orientation issues. Standard navigation
      becomes useless soon after CSF loss due to brain shift. Therefore, the concept of
      "real-time" navigation and intraoperative imaging in combination with endoscopic
      surgery has been previously suggested. The goal of the present study was to
      assess the feasibility and efficacy of combining intraoperative MR (iMR) imaging
      and navigated neuroendoscopy in infants. METHODS: The authors report their
      experience in treating 5 infants (aged 6-14 months), who underwent surgery for
      multicystic hydrocephalus presenting with shunt malfunction (4 patients) and a
      quadrigeminal fetal arachnoid cyst (1 patient). In all infants, a low-field
      portable iMR imaging system (0.12-T PoleStar N-10/0.15-Tesla PoleStar N-20) was
      used in conjunction with navigated endoscopy. The authors used e-steady, T1
      weighted, and T2-weighted sequences (acquisition time 24 seconds to 3.5 minutes).
      RESULTS: The iMR imaging system provided clear images that correlated with the
      endoscopic appearance of the cystic membranes in all patients, and the images
      were helpful in determining trajectories and redefining targets. The iMR images
      documented brain shift and changes in CSF spaces during surgery. There were no
      intraoperative complications or technical difficulties of visualization. No
      infection or any other immediate postoperative complication occurred. Patients
      were followed up for 9 months to 7 years. The infant presenting with the
      quadrigeminal cyst remains shunt free since surgery, and the patients with
      multicystic hydrocephalus have 1-2 shunts each. Following endoscopic, iMR imaging
      guided surgery, shunt catheter positioning was found to be optimal and as planned
      according to the postoperative imaging. CONCLUSIONS: Navigated neuroendoscopy and
      iMR imaging may complement each other, offering an advantage over other
      modalities in complicated cases of hydrocephalus. Whenever targets and
      trajectories need to be redefined, the iMR images provided an updated navigation
      data set, allowing accurate navigation of the endoscope and minimizing the number
      of CSF compartments. Direct vision through the endoscope provides microanatomical
      details for the optimization of fenestration and catheter positioning. The
      combined usage of the two modalities may transform a conventional procedure into
      a visually controlled real-time navigated process.

PMID- 21882921
TI  - Hydrocephalus status in spina bifida: an evaluation of variations in
      neuropsychological outcomes.
AB  - OBJECT: The effect of hydrocephalus status on neuropsychological outcomes in
      children with spina bifida (SB) has not been carefully evaluated. The authors
      hypothesized a stepwise progression of outcomes related to hydrocephalus status
      (shunt-treated, arrested, or no hydrocephalus) and that motor, spatial, and
      executive function tasks would be more sensitive to hydrocephalus status than
      vocabulary and reading tasks. METHODS: Two hundred eight children (mean age 11.2
      years) with SB were grouped according to hydrocephalus status: shunt-treated
      hydrocephalus (166 children), arrested hydrocephalus (18 children), and no
      hydrocephalus (24 children). Sixty-one typically developing children were
      included as a control group (mean age 12.05 years). All children were tested
      across neuropsychological content domains, including verbal and nonverbal IQ,
      reading and mathematical achievement, explicit memory, visuospatial function,
      executive function, and motor skills. RESULTS: There was a stepwise progression
      of outcomes. Averaging across tasks, performance scores of children with SB and
      no hydrocephalus (mean standard score 92.60) were higher than those of children
      with SB and arrested hydrocephalus (mean standard score 86.86), and scores of
      children in the latter group were higher than those of children with SB and shunt
      treated hydrocephalus (mean standard score 82.30). All 3 groups scored lower than
      the control group (mean standard score 105.94). Fine motor tasks best
      differentiated the arrested-hydrocephalus and shunt-treated groups. Verbal and
      executive function tasks, often associated with socioeconomic status, best
      differentiated the group of children with SB and no hydrocephalus from the
      control group. CONCLUSIONS: With the exception of fine motor skills and small
      differences in memory and spatial domains, children with SB and arrested or shunt
      treated hydrocephalus have similar neuropsychological profiles. Performance of
      all 3 groups of children with SB was below that of the control group, which also
      reflects the lower socioeconomic status of the children with SB.

PMID- 21882922
TI  - A sacral arachnoid cyst causing holocord syringomyelia.
AB  - Spinal extradural arachnoid cysts (ACs) have an infrequent predilection for the
      sacrum. As with their counterparts in other regions of the spine, cysts in this
      location are mostly asymptomatic. Common presentations in symptomatic cases
      include pain in the low back or perineum, radiculopathy, and sphincteric
      dysfunction. The authors report a hitherto undescribed presentation in which the
      predominant symptoms are those related to an associated holocord syrinx. This 15
      year-old boy presented with fluctuating, spastic paraparesis and a dissociated
      sensory loss in the trunk. Admission MR imaging of the spine showed an extradural
      AC from S-2 to S-4 and a holocord, nonenhancing syrinx. The patient underwent S-2
      laminectomy, fenestration of the cyst, and partial excision of its wall.
      Intradural exploration revealed a normal-looking filum terminale and the absence
      of any dural communication with the cyst. At a follow-up visit 6 months after
      surgery, his motor and sensory deficits had resolved. Follow-up MR imaging showed
      complete resolution of the syrinx in the absence of the sacral AC. This is the
      first report of a sacral extradural AC causing holocord syringomyelia. Because
      conventional theories of syrinx formation were not helpful in elucidating this
      case, a hypothesis is postulated to explain the clinicoradiological oddity.

PMID- 21882923
TI  - Long-term social outcome in children with moyamoya disease who have reached
      adulthood.
AB  - OBJECT: Although the reported surgical outcome is favorable, there is little
      information regarding the long-term quality of life in pediatric patients with
      moyamoya disease (MMD) when they grow to adulthood. The authors conducted a
      survey to provide details of social adaptation and satisfaction in adults who
      underwent revascularization surgery for MMD during childhood. METHODS: One
      hundred twenty-three patients with MMD who had undergone surgery during childhood
      and were older than 18 years of age were recruited for this study. The authors
      mailed self-administered questionnaires regarding each patient's education,
      employment, marriage, driver's license, physical condition, and satisfaction.
      Sixty-five patients (53%) responded. RESULTS: Compared with the general
      population, the patients showed a similar rate of attaining a higher education.
      Forty-nine (80%) of 61 patients who were not currently high school students had
      entered college or university. However, the presence of neurological deficits on
      preoperative examination was a negative predictor of entrance into a college or
      university, as well as employment. Some patients had difficulty in planning
      marriage because of physical handicaps, and the rate of acquiring a driver's
      license and actual driving were relatively low. Approximately 80% of the
      responders were satisfied with their treatment outcomes, but more than one-half
      reported subjectively assessed neurological problems. CONCLUSIONS: In this study,
      pediatric patients with MMD showed favorable social adaptation in adulthood. The
      findings also indicated that early diagnosis and intervention before the
      establishment of neurological deficits are essential to children with MMD in
      becoming better socially adapted. Further, more thorough clinical examinations
      are required during follow-up in patients with MMD.

PMID- 21882924
TI  - Severely impaired cerebrovascular reserve in patients with cerebral proliferative
      angiopathy.
AB  - OBJECT: Cerebral proliferative angiopathy (CPA) has been morphologically
      distinguished from classically appearing brain arteriovenous malformations (AVMs)
      by exhibition of functional brain parenchyma that is intermingled with abnormal
      vascular channels. The presence of oligemia in this intralesional brain tissue
      may suggest ischemia, which is not detected in classic brain AVMs. The authors
      hypothesized that patients with CPA would exhibit a greater impairment of
      cerebrovascular reserve in neuronal tissue surrounding the true nidus compared
      with those with brain AVMs. METHODS: Four patients with CPA, 10 patients with
      brain AVMs and seizures, and 12 young healthy individuals were studied. The 4
      patients with CPA underwent blood oxygen level-dependent MR imaging examinations
      while applying normoxic step changes in end-tidal CO(2) to obtain quantitative
      cerebrovascular reactivity measurements. RESULTS: Patients with a CPA lesion
      exhibited severely impaired perilesional cerebrovascular reserve in comparison
      with patients with brain AVMs and seizures (0.10 +/- 0.03 vs 0.16 +/- 0.03,
      respectively; p < 0.05), and young healthy individuals (0.10 +/- 0.03 vs 0.21 +/-
      0.06, respectively; p < 0.01). CONCLUSIONS: This study demonstrated severely
      impaired cerebrovascular reserve in the perilesional brain tissue surrounding the
      abnormal vessels of patients with CPA. This finding may provide an additional
      means to distinguish CPA from classic brain AVMs.

PMID- 21882925
TI  - Encephalocraniocutaneous lipomatosis: a review of its clinical pathology and
      neurosurgical indications.
AB  - Encephalocraniocutaneous lipomatosis (ECCL) is a rare neurocutaneous syndrome
      whose hallmark lesions are benign lipomas of the brain and spinal cord. The
      authors present a case of a male infant with ECCL who had extensive brainstem and
      spinal cord lipomas. The management of this patient's hydrocephalus,
      cervicomedullary compression, tethered cord, and scoliosis over the course of his
      first 2 years of life is described. This case report and review of the literature
      is presented to provide a synopsis of the problems likely to be encountered by
      neurosurgeons who treat patients with this syndrome.

PMID- 21882926
TI  - Growing mammary choristoma masquerading as a lumbosacral lipomyelomeningocele in
      a pubertal girl.
AB  - The authors report, to the best of their knowledge, the first case of lumbosacral
      choristoma of breast origin, presenting in a young girl with lumbosacral
      lipomyelomeningocele. Although choristomas are considered to be benign, the
      regrowth of this mass when the patient was 15 and 16 years of age, and its
      involvement in the conus medullaris and cauda equina, warranted 2 additional
      resections with spinal cordotomy resulting in cessation of any further growth.
      The authors describe the case and provide a review of pertinent literature and a
      discussion of the mechanisms involving the development and growth of this lesion.

PMID- 21882927
TI  - Amenorrhea complicating endoscopic third ventriculostomy in the pediatric age
      group.
AB  - Endoscopic third ventriculostomy (ETV) is an accepted option in the treatment of
      obstructive hydrocephalus in children and is considered by many pediatric
      neurosurgeons to be the treatment of choice in this population. The procedure
      involves perforation of the floor of the third ventricle, specifically, the tuber
      cinereum, which is part of the hypothalamic-pituitary axis of cerebral endocrine
      regulation. Endocrine dysfunction, such as amenorrhea, weight gain, and
      precocious puberty, which are recognized only months to years after the
      procedure, may be underreported because patients and physicians may not relate
      the endocrine sequelae to the ETV. Few detailed reports of endocrine-related
      complications following ETV exist to better understand these issues. In this
      study, the authors add to the literature with case descriptions of and
      correlative laboratory findings in 2 adolescent girls who underwent ETV for
      obstructive hydrocephalus and in whom amenorrhea subsequently developed.

PMID- 21882928
TI  - Are ultrasonography measurements of optic nerve sheath diameter an alternative to
      funduscopy in children with syndromic craniosynostosis?
AB  - OBJECT: Children with syndromic or complex craniosynostosis are evaluated for
      increased intracranial pressure (ICP) using funduscopy to detect papilledema.
      However, papilledema is a late sign of increased ICP. Because papilledema might
      be preceded by an increase in optic nerve sheath (ONS) diameter, the authors
      conducted a prospective study to establish the validity and applicability of
      measuring the ONS using ultrasonography. METHODS: From January 2007 to December
      2009, 175 bilateral ultrasonography ONS measurements were performed in 128
      patients with syndromic or complex craniosynostosis during the daytime. The
      measurements were correlated with ONS diameter assessed on CT and simultaneous
      funduscopy, when available. Furthermore, results were compared by using
      thresholds for ONS diameters on ultrasonography that are available in the
      literature. RESULTS: The mean ONS diameter on ultrasonography was 3.1 +/- 0.5 mm.
      The CT measurement was significantly correlated with the ultrasonography
      measurement (r = 0.41, p < 0.001). The mean ONS diameter in 38 eyes with
      papilledema was 3.3 +/- 0.5 mm, compared with 3.1 +/- 0.5 mm in the eyes of
      patients without papilledema (p = 0.039). Relative to the age-related thresholds,
      the ONS diameter was too large in 11 eyes (3%), particularly in patients with
      Crouzon syndrome. Compared with funduscopy, ultrasonography sensitivity was 11%,
      specificity was 97%, and positive and negative predictive values were 40% and
      86%, respectively. CONCLUSIONS: Ultrasonography is a valid and easy way of
      quantifying the ONS. Although the ONS diameter is larger in children with
      papilledema, it cannot be used as a daytime screening tool instead of funduscopy.
      The ONS diameter is possibly a more real-time indicator of ICP.

PMID- 21882929
TI  - Cerebellopontine angle cyst.

PMID- 21882930
TI  - Validity of the Psycho-Oncology Screening Tool (POST).
AB  - Identifying cancer patients who are experiencing psychosocial challenges during
      the early phase of oncology treatment can prevent escalating patient distress.
      Standardized screening methods allow the medical team to identify those at high
      risk for poor adjustment. The purpose of this study was to provide preliminary
      psychometric evidence for a brief, self-administered screening instrument, the
      Psycho-Oncology Screening Tool (POST), designed to evaluate emotional and
      physical distress, depressive symptoms, and social concerns. Participants
      included 944 radiation oncology patients who completed the POST prior to their
      treatment appointment and a subgroup of 516 patients who completed the POST and
      one of six concurrent validity measures. Psychometric analysis included construct
      validity evidence provided through confirmatory factor analysis (CFA), internal
      reliability estimates, and concurrent validity estimates assessed with bivariate
      correlations between POST subscales scores and conceptually similar established
      measures. A three-factor CFA model was found to produce acceptable model fit,
      supporting the three domain structure of the POST. Furthermore, the three
      subscales--emotional and physical distress, depressive symptoms and social
      concerns--were found to produce acceptable internal reliability estimates (alpha
      = .73-.88). Concurrent validity evidence was observed with significant, moderate
      to large correlations between the POST subscales and all relevant measures (i.e.,
      Profile of Mood States, Hospital Anxiety and Depression Scale, Functional
      Assessment of Cancer Therapy Fatigue, Beck Depression Inventory, Pain Disability
      Index, and the Interpersonal Support Evaluation List) with correlations ranged
      from 0.42 to 0.83, p < 0.01. Patients and clinic staff reported no problems
      administering or completing the POST. Results of this study support the
      psychometric soundness as well as the feasibility and acceptability of the POST
      as a brief screening tool for oncology patients receiving outpatient services.

PMID- 21882931
TI  - Analysis of memory deficits following chemotherapy in breast cancer survivors:
      evidence from the doors and people test.
AB  - Studies of cognitive effects of chemotherapy among breast cancer patients show
      that not all women who are exposed to chemotherapy develop cognitive dysfunction
      and that the observed declines in cognitive functioning may be quite subtle. The
      use of measures that are sensitive to subtle cognitive decline are recommended
      yet rarely used among clinical populations. The purpose of this study is to
      specify the types of memory changes observed among breast cancer survivors
      treated with chemotherapy and tamoxifen, by using an analytic test of memory, the
      Doors and People test, which uses age-adjusted norms. The participants were 40
      women who were survivors of breast cancer, 20 of whom had completed chemotherapy
      treatment and 20 women who were treated only with tamoxifen. There were no
      significant differences between the two groups in overall scores and in all four
      subtests: visual memory, verbal memory, recall, and recognition measured by age
      adjusted scores. Forty percent of patients in both of the groups were classified
      as having mild impairment in episodic memory. No between-group differences were
      found in the frequency of subjective, cognitive complaints. Subjective complaints
      were reported by 69% of patients but were unrelated to objective performance.
      Memory deficits were observed in breast cancer patients who receive either
      chemotherapy or tamoxifen alone compared to age-adjusted norms. The Doors and
      People Test is a sensitive measure of memory deficits that is feasible for use
      with clinical populations of breast cancer patients in order to monitor changes
      in cognitive function.

PMID- 21882932
TI  - Psychosocial adjustment among low-income Latina cervical cancer patients.
AB  - Cancer-related coping strategies and social support, life stress, and optimism
      were tested in regression analyses as predictors of depression, affect, and
      quality of life among 54 low-income, immigrant Latina cervical cancer patients.
      Sixty-seven percent of the patients endorsed symptoms similar to diagnosable
      depression. Predictors significantly accounted for 35% to 54% of the variance in
      outcomes. Cancer-related coping strategies were found to mediate several of the
      relations between life stress, social support, and optimism and outcomes.
      Findings emphasize the need to consider the context within which patients live
      when assessing adjustment to cancer and developing culturally-sensitive
      interventions.

PMID- 21882933
TI  - Gynecological cancer survivors: assessment of psychological distress and unmet
      supportive care needs.
AB  - This study highlights psychosocial needs of gynecological cancer survivors,
      contributing to evaluation of the Cancer Survivors Unmet Needs measure. Of the 45
      participants, 28.9% reported clinical anxiety, 20.0% mild-to-severe depression,
      and 15.6% had probable posttraumatic stress disorder. Strength of unmet needs was
      associated with anxiety, depression, posttraumatic stress, poorer quality of
      life, younger age, and greater time since diagnosis. Linear regressions showed
      clinical measures, quality of life, optimism, and self-blaming coping style
      explained 56.4% of strength of unmet needs. Anxiety, functional well-being,
      posttraumatic stress, and emotional well-being accounted for 40.7% of variance in
      fear of recurrence, with emotional well-being the strongest predictor.

PMID- 21882934
TI  - Stage of disease progression moderates the association between social support and
      depression in prostate cancer survivors.
AB  - This study was designed to test the association between social support and
      depression at different stages of disease progression in men with prostate
      cancer.Seventy-one men with prostate cancer completed measures of social support
      and depression three times: T1 (at baseline), T2 (T1 + 2 months), and at T3 (T1 +
      4 months). Stage of disease progression was significantly associated with
      increasing symptoms of depression. Stage of disease progression also moderated
      the association between social support and depression. Social support was
      associated with a subsequent worsening of depression for men with early-stage
      disease. For men with more advanced prostate cancer, social support was
      associated with improvements in subsequent depression. Social support has
      different prognostic value for psychological distress among men with prostate
      cancer depending upon the stage of their disease.

PMID- 21882935
TI  - Posttraumatic growth in women one year after diagnosis for gynecologic cancer or
      benign conditions.
AB  - The authors sought to examine levels and predictors of posttraumatic growth over
      one year after surgery in women diagnosed with gynecologic cancer or benign
      conditions necessitating surgical intervention. Women with advanced-stage cancer
      (n = 16), early-stage cancer (n = 18), benign gynecologic disease (n = 21), and
      no disease (n = 14; postannual pelvic exam) completed questionnaires (Perceived
      Threat, PTSD Checklist [PCL]) 1 week prior to surgery and completed the
      Posttraumatic Growth Inventory (PTGI) 16 months postsurgery. The four groups'
      scores varied significantly on the PTGI. The three disease groups reported higher
      levels of posttraumatic growth than the no disease group. Higher PCL score
      presurgery and greater disease severity were positively related to posttraumatic
      growth, and higher income level was negatively related to posttraumatic growth.
      Women with gynecologic cancer, regardless of stage, and women with benign
      gynecologic conditions experience posttraumatic growth.

PMID- 21882936
TI  - I am proud and hopeful: age-based comparisons in positive coping affect among
      women who use online peer-support.
AB  - How do women who seek psychosocial support on the Internet by participating in
      cancer peer support groups respond to the process of coping with cancer? The
      current study examines whether older women with cancer have different perceptions
      about and are influenced to a different extent by online peer support than
      younger women. The study also explores age-based variations in outlook on coping
      with cancer as a result of using online support. Separate multivariate regression
      models estimated the effects of covariates on (1) positive coping affect (PCA)
      (2) positive coping affect-hopeful (PCA-H), and (3) positive coping affect-proud
      (PCA-P). A stratified analysis examined variations within age-based subsamples
      (>=51 and <=50). Positive coping affect includes feeling proud about coping with
      cancer from a position of strength and empowerment rather than being a victim and
      being hopeful for a healthier future postdiagnosis. Online support was found to
      increase PCA significantly. This finding is consistent across age groups but was
      more pronounced for older patients. The only exception is that younger women
      perceive more benefit from using online support in terms of feeling proud. As
      severity of the symptoms increased, though the younger women increased the amount
      of time they were online, the older women increased the number of groups they
      participated in. The study concludes that the Internet might be particularly
      helpful for older adults who feel helpless to cope with cancer in old age. Online
      peer support services may help improve the patients' outlook on fighting with
      cancer and help them to feel more in control of their health.

PMID- 21882937
TI  - Ethical issues related to clinical trials outside the International Conference on
      Harmonization regions.

PMID- 21882939
TI  - Cambridge Healthtech Institute Drug Discovery Chemistry. San Diego, CA, USA, 12
      14 April, 2011.

PMID- 21882940
TI  - The role of solvent selection at exploratory and production stages in the
      pharmaceutical industry.

PMID- 21882942
TI  - Conformational adaptation in drug-target interactions and residence time.
AB  - Although drug-target interactions are commonly illustrated in terms of
      structurally static binding and dissociation events, such descriptions are
      inadequate to explain the impact of conformational dynamics on these processes.
      For high-affinity interactions, both the association and dissociation of drug
      molecules to and from their targets are often controlled by conformational
      changes of the target. Conformational adaptation can greatly influence the
      residence time of a drug on its target (i.e., the lifetime of the binary drug
      target complex); long residence time can lead to sustained pharmacology and may
      also mitigate off-target toxicity. In this perspective, the kinetics of drug
      target association and dissociation reactions are explored, with particular
      emphasis on the impact of conformational adaptation on drug-target residence
      time.

PMID- 21882941
TI  - Marine natural products: a new wave of drugs?
AB  - The largely unexplored marine world that presumably harbors the most biodiversity
      may be the vastest resource to discover novel 'validated' structures with novel
      modes of action that cover biologically relevant chemical space. Several
      challenges, including the supply problem and target identification, need to be
      met for successful drug development of these often complex molecules; however,
      approaches are available to overcome the hurdles. Advances in technologies such
      as sampling strategies, nanoscale NMR for structure determination, total chemical
      synthesis, fermentation and biotechnology are all crucial to the success of
      marine natural products as drug leads. We illustrate the high degree of
      innovation in the field of marine natural products, which in our view will lead
      to a new wave of drugs that flow into the market and pharmacies in the future.

PMID- 21882943
TI  - Predicting in vivo safety characteristics using physiochemical properties and in
      vitro assays.
AB  - There is increasing pressure on the pharmaceutical industry to deliver safer and
      more effective medicines while constraining research and development costs. In
      order to meet these demands, the industry is looking for basic design principles
      in terms of physicochemical properties as well as the use of higher throughput in
      vitro assays to select and evaluate new molecular entities for further
      development. Recent advances in understanding the relationships between a
      chemical's properties and its propensity for adverse events, as well as the
      development of new in vitro screening technologies, have enhanced our ability to
      potentially select molecules more likely to succeed in becoming drugs. However,
      these approaches are still limited by the availability of data and our lack of
      understanding of the mechanisms by which compounds can cause toxicity.

PMID- 21882944
TI  - Iminosugars as therapeutic agents: recent advances and promising trends.
AB  - For the purpose of this article, iminosugars are polyhydroxylated secondary and
      tertiary amines in which the molecules resemble monosaccharide sugars in which
      the ring oxygen is replaced by the nitrogen. The bicyclic structures may
      biologically resemble disaccharides. Very few iminosugars have been available up
      to now for evaluation of their pharmaceutical applications. The early compounds
      were discovered and selected for study due to glycosidase inhibition, which is
      now known to not be necessary for pharmacological activity and may cause off
      target effects. Glyset(r) and Zavesca(r), derived from the glucosidase-inhibiting
      natural product 1-deoxynojirimycin, are the first two examples of iminosugar
      drugs. Since the discovery of this first generation, many new natural products
      have been identified with a wide range of biological activities but few are
      widely available. Among the biological properties of these compounds are good
      oral bioavailability and very specific immune modulatory and chaperoning
      activity. Although the natural products from plants and microorganisms can have
      good specificity, modifications of the template natural products have been very
      successful recently in producing bioactive compounds with good profiles. The
      field of iminosugars continues to open up exciting new opportunities for
      therapeutic agent discovery and offers many new tools for precisely modifying
      carbohydrate structures and modulating glycosidase activity in vivo. Current
      efforts are directed towards a greater range of structures and a wider range of
      biochemical targets.

PMID- 21882946
TI  - Discovering small molecules to control stem cell fate.
AB  - Pluripotent stem cells promise to revolutionize drug discovery and offer new
      modes of therapy. The ease with which they can be grown in bulk and their
      differentiation controlled in vitro is of importance for their widespread
      adoption by industry and their clinical efficacy. Small molecules have already
      had a positive impact on several areas of stem cell biology, from maintenance of
      pluripotency, the promotion of single cell survival and steering differentiation
      to involvement in reprogramming somatic cells. High-throughput technology has
      played an important role in identifying novel compounds, however to date there
      are few published examples of medicinal chemistry input in this area. This review
      discusses the potential of pluripotent stem cells, the successful uses of small
      molecules and future prospects.

PMID- 21882947
TI  - Cyclin-dependent kinases: bridging their structure and function through
      computations.
AB  - Cyclin-dependent kinases (CDKs) are one of the most promising target families for
      drug discovery for several diseases, such as cancer and neurodegenerative
      disorders. Over the years, structural insights on CDKs have demonstrated high
      protein plasticity, with several cases where two or more structures of the same
      protein adopt different conformations. This has generated a great deal of
      interest in understanding the relationship between CDK structure and function.
      Here, we highlight how computer simulations have recently contributed in
      characterizing some key rare and transient events in CDKs, such as the reaction
      transition state and activation loop movement. Although not yet fully defined, we
      can now portray the enzymatic mechanism and plasticity of CDKs at high spatial
      and temporal resolution. These theoretical studies bridge with experiments and
      highlight structural determinants that could help in designing specific CDK
      inhibitors.

PMID- 21882950
TI  - Attempt to develop taste bud models in three-dimensional culture.
AB  - Taste buds are the end organs of taste located in the gustatory papillae, which
      occur on the surface of the oral cavity. The goal of the present study was to
      establish a culture model mimicking the lingual taste bud of the mouse. To this
      end, three cell lines were employed: taste bud-derived cell lines (TBD cell
      lines), a lingual epithelial cell-derived cell line (20A cell line), and a
      mesenchymal cell-derived cell line (TMD cell line). TBD cells embedded in
      collagen gel formed three-dimensional clusters, which had an internal cavity
      equipped with a tight junction-like structure, a microvilluslike structure, and a
      laminin-positive layer surrounding the cluster. The cells with this
      epitheliumlike morphology expressed marker proteins of taste cells: gustducin and
      NCAM. TBD cells formed a monolayer on collagen gel when they were co-cultured
      with TMD cells. TBD, 20A, and TMD cell lines were maintained in a triple cell co
      culture, in which TBD cells were pre-seeded as aggregates or in suspension on the
      collagen gel containing TMD cells, and 20A cells were laid over the TBD cells.
      TBD cells in the triple cell co-culture expressed NCAM. This result suggests that
      co-cultured TBD cells exhibited a characteristic of Type III taste cells. The
      culture model would be useful to study morphogenesis and functions of the
      gustatory organ.

PMID- 21882951
TI  - Exposure to external environment of low ion concentrations is the trigger for
      rapid wound closure in Xenopus laevis embryos.
AB  - Wounds in Xenopus laevis embryos close rapidly, as previously described. In this
      study, we examined the dependence on extracellular Na(+) and/or Cl(-) ion
      concentrations of the closure of wounds in Xenopus embryos inflicted by thermal
      injury. Wound closure did not occur in normal amphibian medium (100% NAM), while
      wound areas remarkably decreased either in 10-50% NAM or in 100% NAM lacking
      Na(+) or Cl(-). Similarly, wound areas did not change in a set of Na(+) and Cl(-)
      ion concentrations equivalent to those of the humoral fluids of intact Xenopus
      embryos, but rapid wound closure was induced by decreasing the concentration of
      either of the two ions. A tangential accumulation of actin cytoskeleton along the
      wound edge was associated with wound closure. However, a similar actin alignment
      formed even under the 100% NAM condition, in which wounds did not close, as
      stated above. The epidermis around the wound edge exhibited ellipse-shaped
      hypertrophy, and the marginal cells centripetally elongated during wound closure.
      On the other hand, no distinct morphological changes occurred in 100% NAM,
      although the epidermis was somewhat thickened. Thus, the morphological changes in
      the epidermis specific to the low ionic environment most likely play active roles
      in the wound closure of Xenopus laevis embryos, whereas the tangential actin
      alignment alone may be insufficient. Taken together, we propose that the wound
      closure in Xenopus embryos is triggered by a decline in either the extracellular
      Na(+) or Cl(-) ion concentration, and that this process is required for the
      abovementioned changes in the shape of the marginal cells.

PMID- 21882952
TI  - Population structure in the endangered cyprinid fish Pararasbora moltrechti in
      Taiwan, based on mitochondrial and microsatellite DNAs.
AB  - The genetic structure of four populations of Pararasbora moltrechti, an endemic
      species of the Cyprinidae in Taiwan, was investigated based on the genetic
      variation of mtDNA Cyt b gene and five microsatellite loci. High haplotype
      diversity (h = 0.92) but low nucleotide diversity (0.004) in mtDNA was detected
      in this endangered species. In total, 33 haplotypes and four clusters were
      identified in its mtDNA. Nevertheless, low correspondence was found between
      geographical division and mtDNA clusters. In contrast, Bayesian cluster analysis
      of the microsatellite data identified four genetic groups and revealed highly
      structured populations. Significantly negative Tajima's D statistics and mismatch
      distribution analyses suggest that P. moltrechti populations may have experienced
      a demographic expansion. In light of the results of a nested clade analysis of
      mtDNA haplotypes, we conclude that recent population fluctuations and restricted
      gene flow played major roles in shaping the spatial genetic structure of P.
      moltrechti populations.

PMID- 21882945
TI  - Molecular chaperones and regulation of tau quality control: strategies for drug
      discovery in tauopathies.
AB  - Tau is a microtubule-associated protein that accumulates in at least 15 different
      neurodegenerative disorders, which are collectively referred to as tauopathies.
      In these diseases, tau is often hyperphosphorylated and found in aggregates,
      including paired helical filaments, neurofibrillary tangles and other abnormal
      oligomers. Tau aggregates are associated with neuron loss and cognitive decline,
      which suggests that this protein can somehow evade normal quality control
      allowing it to aberrantly accumulate and become proteotoxic. Consistent with this
      idea, recent studies have shown that molecular chaperones, such as heat shock
      protein 70 and heat shock protein 90, counteract tau accumulation and
      neurodegeneration in disease models. These molecular chaperones are major
      components of the protein quality control systems and they are specifically
      involved in the decision to retain or degrade many proteins, including tau and
      its modified variants. Thus, one potential way to treat tauopathies might be to
      either accelerate interactions of abnormal tau with these quality control factors
      or tip the balance of triage towards tau degradation. In this review, we
      summarize recent findings and suggest models for therapeutic intervention.

PMID- 21882953
TI  - Phylogeography of Japanese population of Phelotrupes auratus (Coleoptera,
      Geotrupidae) inferred from mitochondrial DNA sequences.
AB  - A partial sequence of the mitochondrial cytochrome c oxidase subunit I (COI) gene
      (745 bp) was determined for 57 specimens of a geotrupid beetle (Phelotrupes
      auratus) from throughout the Japanese archipelago. Of the 57 beetles examined, 42
      haplotypes were identified. Phylogenetic trees inferred using maximum parsimony,
      neighbor joining, and Bayesian inference methods were highly congruent.
      Reconstructed phylogenetic relationships indicated that P. auratus from the
      Japanese archipelago was separated into two distinct lineages: Group A, which
      consisted of 35 haplotypes from Honshu, Shikoku, and Hokkaido Islands, and Group
      B, which consisted of seven haplotypes from Kyushu and Yakushima Islands. In
      addition, two sublineages were also recognized within Group A: Subgroup A-1,
      which consisted of 11 haplotypes from eastern Honshu and Hokkaido, and Subgroup A
      2, which consisted of 10 haplotypes from western Honshu and Shikoku. Average
      genetic distances within Group A were positively correlated to geographic
      distance between sampling localities. Phylogenetic relationships among haplotypes
      did not correspond to subspecies classification.

PMID- 21882954
TI  - Male aggressive behavior and exaggerated hindlegs of the bean bug Riptortus
      pedestris.
AB  - Males of the bean bug species Riptortus pedestris possess larger hindlegs than
      females. Observations of male-male interactions showed that the enlarged hindlegs
      are used as weapons in male fights, and that males with larger hindlegs win
      fights more frequently. Morphological analysis based on the positive allometry
      test showed that the femora of larger males are relatively bigger than those of
      smaller males, but femora of larger females are not relatively larger than those
      of smaller females. These results suggest that sexual selection in R. pedestris
      favors larger hindlegs for male fighting. In addition, the thorax and abdomen
      lengths were larger in the male than in the female. The males often lift their
      abdomen with their back to the opponent for displays against an opponent. As a
      result, abdominal size may be under stronger selection in the male than in the
      female, as for the exaggerated hindlegs.

PMID- 21882955
TI  - Localization of water channels in the skin of two species of desert toads,
      Anaxyrus (Bufo) punctatus and Incilius (Bufo) alvarius.
AB  - Anuran amphibians obtain water by osmosis across their ventral skin. A
      specialized region in the pelvic skin of semiterrestrial species, termed the seat
      patch, contains aquaporins (AQPs) that become inserted into the apical plasma
      membrane of the epidermis following stimulation by arginine vasotocin (AVT) to
      facilitate rehydration. Two AVT-stimulated AQPs, AQP-h2 and AQP-h3, have been
      identified in the epidermis of seat patch skin of the Japanese tree frog, Hyla
      japonica, and show a high degree of homology with those of bufonid species. We
      used antibodies raised against AQP-h2 and AQP-h3 to characterize the expression
      of homologous AQPs in the skin of two species of toads that inhabit arid desert
      regions of southwestern North America. Western blot analysis of proteins gave
      positive results for AQP-h2-like proteins in the pelvic skin and also the urinary
      bladder of Anaxyrus (Bufo) punctatus while AQP-h3-like proteins were found in
      extracts from the pelvic skin and the more anterior ventral skin, but not the
      urinary bladder. Immunohistochemical observations showed both AQP-h2- and AQP-h3
      like proteins were present in the apical membrane of skin from the pelvic skin of
      hydrated and dehydrated A. punctatus. Further stimulation by AVT or isoproterenol
      treatment of living toads was not evident. In contrast, skin from hydrated
      Incilius (Bufo) alvarius showed very weak labeling of AQP-h2- and AQP-h3-like
      proteins and labeling turned intense following stimulation by AVT. These results
      are similar to those of tree frogs and toads that occupy mesic habitats and
      suggest this pattern of AQP expression is the result of phylogenetic factors
      shared by hylid and bufonid anurans.

PMID- 21882956
TI  - Molecular characterization of alternative transcripts of the horse BMAL1 gene.
AB  - The horse BMAL1 gene encodes the brain and muscle Arnt-like protein 1, which is a
      key regulator of circadian rhythmic systems in most organs and cells. The first
      exon of the horse-specific BMAL1 gene is produced by an exonization event of
      LINE3 (CR1) and SINE (MIR) was detected by bioinformatic analysis. Alternative
      variants generated by cassette exon event in various horse tissues were also
      detected by RT-PCR amplification and sequencing. The cDNA sequences of the horse
      transcripts (BMAL1a, BMAL1b) contain additional 21 bp and 71 bp fragments
      relative to horse BMAL1. Quantitative real-time RT-PCR was performed to compare
      the expression patterns between transcript variants in various horse tissues. The
      results of these experiments showed splice variants that were widely expressed in
      most tissues. Furthermore, they were highly expressed in cerebellum, heart, and
      kidney.

PMID- 21882957
TI  - Allometric comparison of skulls from two closely related weasels, Mustela itatsi
      and M. sibirica.
AB  - We conducted an interspecific comparison of skulls from two closely related but
      differently sized mustelid species, Mustela itatsi and M. sibirica (Mammalia,
      Carnivora, Mustelidae); a sexual comparison within the latter species showed
      remarkable size dimorphism. We clarified several differences in skull proportion
      related to size using allometric analyses and qualitative comparisons. Allometric
      analysis revealed that the skulls of male M. itatsi (the smaller species) have a
      relatively long palate; a slender viscerocranium and postorbital constriction; a
      broad, short, and low neurocranium; small carnassials; and a short mandible with
      a thin body and small ramus compared to the skulls of male M. sibirica (the
      larger species). Similar results were obtained when male M. itatsi were compared
      to female M. sibirica, although the male M. itatsi had a broader viscerocranium
      than female M. sibirica. A sexual comparison in M. sibirica revealed a larger
      skull size among the males with a relatively wide viscerocranium; wide
      postorbital constriction; a slender, long, and high neurocranium; short and wide
      auditory bullae; short carnassials; and a long and high mandible compared to
      females. Qualitative comparisons revealed changes in a few characters depending
      on skull size or with respect to some cranial components in each species. The
      interspecific differences observed were clearly larger than the intraspecific
      differences for three qualitative characters. The allometric and qualitative
      differences detected between these species suggest that each species is not
      simply the dwarf and/or giant morph of the other, and complicated differences
      were clarified.

PMID- 21882958
TI  - Spermiophagy in the male reproductive tract of some passerine birds.
AB  - In order to elucidate the locus and means of spermiophagy in passerine birds, we
      examined histologically the entire male reproductive tract of sexually mature
      birds of three passerine species with different forms of sperm competition,
      namely, the alpine accentor (Prunella collaris), the redflanked bush robin
      (Tarsiger cyanurus), and the Bengalese finch (Lonchura striata var. domestica).
      Spermiophagy occurred consistently and frequently in the epithelial layer of the
      seminal glomera and ejaculatory duct in each species, which were regularly
      identified by non-ciliated epithelial cells. The epithelial spermiophagy was
      occasional or infrequent in other portions of the seminal tract, and spermiophagy
      by macrophages was uncommon throughout the tract. Quantitative data in the
      seminal glomera and ejaculatory duct gave no clear answer concerning a possible
      relationship between the epithelial spermiophagy and different levels of sperm
      competition among these passerine species. In conclusion, the epithelial lining
      of the terminal region of the seminal tract is the main site for spermiophagy in
      the male reproductive tract of these passerine species, which activity serves to
      maintain the quality of semen by eliminating infertile spermatozoa as well as
      sperm remaining at the end of the breeding season.

PMID- 21882959
TI  - Immunocytochemical localization of calcium-binding proteins, calbindin D28K-,
      calretinin-, and parvalbumin-containing neurons in the dog visual cortex.
AB  - Although the dog is widely used to analyze the function of the brain, it is not
      known whether the distribution of calcium-binding proteins reflects a specific
      pattern in the visual cortex. The distribution of neurons containing calcium
      binding proteins, calbindin D28K, calretinin, and parvalbumin in adult dog visual
      cortex were studied using immunocytochemistry. We also compared this labeling to
      that of gamma-aminobutyric acid (GABA). Calbindin D28K-immunoreactive (IR)
      neurons were predominantly located in layer II/III. Calretinin- and parvalbumin
      IR neurons were located throughout the layers with the highest density in layers
      II/III and IV. The large majority of calbindin D28K-IR neurons were multipolar
      stellate cells. The majority of the calretinin-IR neurons were vertical fusiform
      cells with long processes traveling perpendicular to the pial surface. And the
      large majority of parvalbumin-IR neurons were multipolar stellate and round/oval
      cells. More than 90% of the calretinin- and parvalbumin-IR neurons were double
      labeled with GABA, while approximately 66% of the calbindin D28K-IR neurons
      contained GABA. This study elucidates the neurochemical structure of calcium
      binding proteins. These data will be informative in appreciating the functional
      significance of different laminar distributions of calcium-binding proteins
      between species and the differential vulnerability of calcium-binding proteins
      containing neurons, with regard to calcium-dependent excitotoxic procedures.

PMID- 21882966
TI  - Interagency Biological Restoration Demonstration (IBRD): a collaborative approach
      to biological incident recovery.
AB  - Following the terrorist attacks in 2001, much time and effort has been put toward
      improving catastrophic incident response. But recovery--the period following
      initial response that focuses on the long-term viability of the affected area-
      has received less attention. Recognizing the importance of being able to recover
      an area following a catastrophic incident, the Department of Defense, through its
      Defense Threat Reduction Agency (DTRA), and the Department of Homeland Security,
      through its Science and Technology Directorate (DHS S&T), created the Interagency
      Biological Restoration Demonstration (IBRD) program. IBRD was a 4-year program
      jointly managed and funded by DTRA and DHS S&T, the goal of which was to reduce
      the time and resources necessary to recover a wide urban area from an intentional
      release of Bacillus anthracis. Specific program objectives included understanding
      the social, economic, and operational interdependencies that affect recovery;
      establishing long-term coordination between the Departments of Defense and
      Homeland Security; developing strategic recovery/restoration plans; identifying
      and demonstrating technologies that support recovery; and exercising recovery
      activities and technology solutions. IBRD has made important first steps toward
      improving national preparedness in the area biological incident recovery.
      Specifically, IBRD has helped enhance the efficacy and efficiency of recovering
      large urban areas by developing consequence management guidance; identifying key
      S&T capabilities and integrating them with planning and guidance documents; and
      establishing key relationships across the federal interagency, federal-to
      regional, civilian-to-military, and public-to-private stakeholders. Upon
      completion of IBRD in fall 2010, both DTRA and DHS S&T planned follow-on
      programs.

PMID- 21882964
TI  - Rapidly progressive, fatal, inhalation anthrax-like infection in a human: case
      report, pathogen genome sequencing, pathology, and coordinated response.
AB  - CONTEXT: Ten years ago a bioterrorism event involving Bacillus anthracis spores
      captured the nation's interest, stimulated extensive new research on this
      pathogen, and heightened concern about illegitimate release of infectious agents.
      Sporadic reports have described rare, fulminant, and sometimes fatal cases of
      pneumonia in humans and nonhuman primates caused by strains of Bacillus cereus ,
      a species closely related to Bacillus anthracis. OBJECTIVES: To describe and
      investigate a case of rapidly progressive, fatal, anthrax-like pneumonia and the
      overwhelming infection caused by a Bacillus species of uncertain provenance in a
      patient residing in rural Texas. DESIGN: We characterized the genome of the
      causative strain within days of its recovery from antemortem cultures using next
      generation sequencing and performed immunohistochemistry on tissues obtained at
      autopsy with antibodies directed against virulence proteins of B anthracis and B
      cereus. RESULTS: We discovered that the infection was caused by a previously
      unknown strain of B cereus that was closely related to, but genetically distinct
      from, B anthracis . The strain contains a plasmid similar to pXO1, a genetic
      element encoding anthrax toxin and other known virulence factors.
      Immunohistochemistry demonstrated that several homologs of B anthracis virulence
      proteins were made in infected tissues, likely contributing to the patient's
      death. CONCLUSIONS: Rapid genome sequence analysis permitted us to genetically
      define this strain, rule out the likelihood of bioterrorism, and contribute
      effectively to the institutional response to this event. Our experience strongly
      reinforced the critical value of deploying a well-integrated, anatomic, clinical,
      and genomic strategy to respond rapidly to a potential emerging, infectious
      threat to public health.

PMID- 21882967
TI  - The challenge of determining the need for remediation following a wide-area
      biological release.
AB  - Recovering from a biological attack is a complex process requiring the successful
      resolution of numerous challenges. The Interagency Biological Restoration
      Demonstration program is one of the first multiagency efforts to develop
      strategies and tools that could be effective following a wide-area release of B.
      anthracis spores. Nevertheless, several key policy issues and associated science
      and technology issues still need to be addressed. For example, more refined risk
      assessment and management approaches are needed to help evaluate "true" public
      health risk. Once the risk is understood, that information can be considered
      along with the types of characterization activities deemed necessary to determine
      whether the cost and time of decontamination are actually warranted. This
      commentary offers 5 recommendations associated with decision making regarding
      decontamination and clearance options that should accompany a comprehensive risk
      analysis leading to more effective risk management decisions. It summarizes some
      of the most important technological gaps that still need to be addressed to help
      decision makers in their objective of reducing health risks to an acceptable
      level. The risk management approach described should enable decision makers to
      improve credibility and gain public acceptance, especially when an adequate
      science and technology base is available to support the required decisions.

PMID- 21882968
TI  - The national framework and consequence management guidance following a biological
      attack.
AB  - Consequence management following a release of aerosolized Bacillus anthracis
      spores requires a high level of technical understanding and direction. National
      policies and regulations address the topics of preparedness goals and
      organizational structure, but they do not tell responders how to perform
      remediation. Essential considerations include determining what must be cleaned,
      evaluating health risks, ascertaining the priority of cleanup, and selecting
      appropriate decontamination technologies to meet consensus and risk-derived
      clearance goals. This article highlights key features of a national-level
      framework that has been developed to guide a risk-based decision process and
      inform technical personnel of the best practices to follow during each activity
      leading to the restoration of functions at affected facilities or areas. The
      framework and associated guidance follows the scheme of 6 phases for response and
      recovery arrived at through interagency consensus and approval. Each phase is
      elaborated in a series of detailed decision flowcharts identifying key questions
      that must be addressed and answered from the time that first indications of a
      credible biological attack are received to final reoccupancy of affected areas
      and a return to normal daily functions.

PMID- 21882969
TI  - Developing a regional recovery framework.
AB  - A biological attack would present an unprecedented challenge for local, state,
      and federal agencies, the military, the private sector, and individuals on many
      fronts, ranging from vaccination and treatment to prioritization of cleanup
      actions to waste disposal. To prepare for recovery from this type of incident,
      the Seattle Urban Area Security Initiative (UASI) partners collaborated with
      military and federal agencies to develop a regional recovery framework. The goal
      was to identify key information that will assist policymakers and emergency
      managers in shortening the timeline for recovery and minimizing the economic and
      public health impacts of a catastrophic anthrax attack. Based on discussions in
      workshops, tabletop exercises, and interviews with local, state, federal,
      military, and private sector entities responsible for recovery, the authors
      identified goals, assumptions, and concepts of operation for various areas to
      address critical issues the region will face as recovery progresses. Although the
      framework is specific to a catastrophic, wide-area biological attack using
      anthrax, it was designed to be flexible and scalable so it could also serve as
      the recovery framework for an all-hazards approach in other regions and
      jurisdictions. Benefits from this process include enhanced coordination and
      collaboration across agencies, a more thorough understanding of the anthrax
      threat, an opportunity to proactively consider long-term recovery, and a better
      understanding of the specific policy questions requiring resolution.

PMID- 21882970
TI  - Transport of Bacillus thuringiensis var. kurstaki via fomites.
AB  - The intentional and controlled release of an aerosolized bacterium provides an
      opportunity to investigate the implications of a biological attack. Since 2006,
      Los Alamos National Laboratory has worked with several urban areas, including
      Fairfax County, VA, to design experiments to evaluate biodefense concepts of
      operations using routine spraying of Bacillus thuringiensis var. kurstaki (Btk).
      Btk is dispersed in large quantities as a slurry to control the gypsy moth,
      Lymantria dispar. Understanding whether personnel and equipment pick up residual
      contamination during sampling activities and transport it to other areas is
      critical for the formulation of appropriate response and recovery plans. While
      there is a growing body of literature surrounding the transmission of viral
      diseases via fomites, there is limited information on the transport of Bacillus
      species via this route. In 2008, LANL investigated whether field sampling
      activities conducted near sprayed areas, post-spray, resulted in measurable cross
      contamination of sampling personnel, equipment, vehicles, and hotel rooms. Viable
      Btk was detected in all sample types, indicating transport of the agent occurred
      via fomites.

PMID- 21882971
TI  - A biological decontamination process for small, privately owned buildings.
AB  - An urban wide-area recovery and restoration effort following a large-scale
      biological release will require extensive resources and tax the capabilities of
      government authorities. Further, the number of private decontamination
      contractors available may not be sufficient to respond to the needs. These
      resource limitations could create the need for decontamination by the building
      owner/occupant. This article provides owners/occupants with a simple method to
      decontaminate a building or area following a wide-area release of Bacillus
      anthracis using liquid sporicidal decontamination materials, such as pH-amended
      bleach or activated peroxide; simple application devices; and high-efficiency
      particulate air-filtered vacuums. Owner/occupant decontamination would be
      recommended only after those charged with overseeing decontamination-the Unified
      Command/Incident Command-identify buildings and areas appropriate for
      owner/occupant decontamination based on modeling and environmental sampling and
      conduct health and safety training for cleanup workers.

PMID- 21882972
TI  - Challenges in disposing of anthrax waste.
AB  - Disasters often create large amounts of waste that must be managed as part of
      both immediate response and long-term recovery. While many federal, state, and
      local agencies have debris management plans, these plans often do not address
      chemical, biological, and radiological contamination. The Interagency Biological
      Restoration Demonstration's (IBRD) purpose was to holistically assess all aspects
      of an anthrax incident and assist in the development of a plan for long-term
      recovery. In the case of wide-area anthrax contamination and the follow-on
      response and recovery activities, a significant amount of material would require
      decontamination and disposal. Accordingly, IBRD facilitated the development of
      debris management plans to address contaminated waste through a series of
      interviews and workshops with local, state, and federal representatives. The
      outcome of these discussions was the identification of 3 primary topical areas
      that must be addressed: planning, unresolved research questions, and resolving
      regulatory issues.

PMID- 21882973
TI  - Parasite assemblages of Australian species of Pseudomys (Rodentia: Muridae:
      Murinae).
AB  - The parasite fauna of many Australian rodents is poorly known. The ectoparasite
      and helminth faunas of Pseudomys delicatulus, Pseudomys desertor, Pseudomys
      gracilicaudatus, and Pseudomys hermannsburgensis were determined and compared. In
      total, 12 species of arthropods, 2 cestodes, and 13 nematodes were found. Species
      richness of parasites was highest in P. hermannsburgensis and lowest in P.
      desertor. Despite the sampling effort, the number of parasite species discovered
      did not reach an asymptote for any of the host species, indicating that the full
      parasite fauna was not examined. Helminth species richness was highest in the
      insectivorous P. hermannsburgensis and lower in the obligate herbivores. The
      structure of parasite component communities was influenced by the social
      structure of the host species, not surprisingly, with the most highly social
      species having the highest richness of parasites. Habitat preferences also
      provided contrast between the helminth component communities, with heligmonellid
      nematodes occurring in damp woodlands and dominating the parasite fauna of P.
      gracilicaudatus. Oxyurid nematodes dominated the component communities of the 3
      other species, all of which inhabit drier habitats.

PMID- 21882974
TI  - Direct evidence for Toxoplasma gondii infection in a wild serow (Capricornis
      crispus) from mainland Japan.
AB  - Toxoplasma gondii infection was studied in 41 Japanese serows ( Capricornis
      crispus ), a goat-antelope in mainland Japan. Blood and muscle specimens were
      collected from 41 subjects between 2006 and 2010. Presence of antibodies to T.
      gondii in the sera was examined by using the latex agglutination test (cutoff
      titer 1:32); 10 of 41 (24.4%) were seropositive. Toxoplasma gondii DNA was
      detected in muscle tissue of 1 seropositive serow using a semi-nested PCR assay
      for the B1 gene. A partial nucleotide sequence (220 bp) corresponding to the B1
      gene of T. gondii was obtained by direct sequencing; the sequence was 99.1%
      identical to that of the RH strain. This study is the first report to show direct
      evidence for the T. gondii infection in Japanese serows.

PMID- 21882975
TI  - Three new genera and six new species of lecanicephalideans (Cestoda) from eagle
      rays of the genus Aetomylaeus (Myliobatiformes: Myliobatidae) from northern
      Australia and Borneo.
AB  - New lecanicephalidean cestodes inhabiting the spiral intestine were investigated
      in 4 of the 6 known species of eagle rays of the genus Aetomylaeus Garman. Hosts
      examined consisted of 5 specimens of Aetomylaeus vespertilio from northern
      Australia, 5 of Aetomylaeus maculatus from Borneo, 10 of Aetomylaeus nichofii
      sensu stricto from Borneo, and 7 of Aetomylaeus cf. nichofii 2 from northern
      Australia. As a result of these new collections, 3 new genera and 6 new species
      of lecanicephalideans are formally described. Aetomylaeus vespertilio hosted the
      new genera and species Collicocephalus baggioi n. gen., n. sp. and Rexapex nanus
      n. gen., n. sp., as well as Aberrapex weipaensis n. sp. Aetomylaeus maculatus and
      A. nichofii sensu stricto hosted 3 new species of the novel genus Elicilacunosus
      , with the former eagle ray hosting Elicilacunosus sarawakensis n. sp. and the
      latter hosting both Elicilacunosus dharmadii n. sp. and Elicilacunosus fahmii n.
      sp. No new lecanicephalideans were described from A. cf. nichofii 2.
      Collicocephalus n. gen. is conspicuously unique among the genera of its order in
      possessing a large, retractable apical organ that, in cross-section, is
      transversely oblong, rather than round. Rexapex n. gen. is distinctive in its
      possession of an apical organ that bears 18 papilliform projections around its
      perimeter, and Elicilacunosus n. gen. is unlike any other known
      lecanicephalidean, or eucestode, in its possession of a region of musculo
      glandular tissue along the midline of the dorsal and ventral surfaces of its
      proglottids, manifested externally as a tandem series of depressions. Among other
      features, A. weipaensis n. sp. differs from its congeners in its lack of post
      ovarian vitelline follicles. All 6 new species were each restricted to a single
      species of Aetomylaeus . These records formally establish species of Aetomylaeus
      as hosts of lecanicephalideans. A summary of cestodes of myliobatid rays is
      presented.

PMID- 21882976
TI  - Human and mouse induced pluripotent stem cells are differentially reprogrammed in
      response to kinase inhibitors.
AB  - Conventional human induced pluripotent stem cells (hiPSCs), reprogrammed from
      somatic cells by induced expression of Oct4, Sox2, Klf4, and c-Myc, are
      phenotypically different from mouse embryonic stem cells (ESCs). In mice, culture
      in N2B27 serum-free 2i media (mitogen-activated protein kinase/extracellular
      signal-regulated kinase and glycogen synthase kinase 3 inhibitors; PD0325901 and
      CHIR99021) plus leukemia inhibitory factor (LIF) (2i+LIF medium) enriches for
      germline competent ESCs. Here, we demonstrate that flat-shaped hiPSC colonies can
      be reprogrammed into bowl-shaped multi-potent stem cells (2i-hiPSCs) by using
      2i+LIF medium. Mechanical dissociation of 2i-hiPSC colonies enables stable
      maintenance for >20 passages. Importantly, gene expression profiling demonstrated
      that 2i-hiPSCs more closely resemble primitive neural stem cells (PNSCs).
      Notably, this 2i-induced phenotype was generated from conventional hiPSCs, but
      not human ESCs (hESCs), thus correlating with the observation of neuroectodermal
      SOX1-positive colonies in conventional hiPSCs, but not hESCs in 2i+LIF medium.
      Thus, 2i-hiPSCs, which are nonteratoma forming PNSCs, may represent a safe source
      of cells for neural research and regenerative medicine.

PMID- 21882977
TI  - Anxiety disorders: differential diagnosis and their relationship to chronic pain.
AB  - Anxiety disorders are the most prevalent type of mental disorder, and they
      frequently co-occur with various medical conditions, including chronic pain.
      Anxiety disorders are associated with higher health care costs, and comorbid
      chronic pain and anxiety disorder leads to worse outcomes. Despite their
      prevalence, anxiety disorders often go unrecognized in pain care facilities,
      compromising clinical benefit of pain treatment. Differential diagnosis among the
      anxiety disorders can be very difficult, and the high comorbidity with mood
      disorders, unexplained physical symptoms, and medical disorder makes the precise
      assessment complicated. Nevertheless, a better understanding of the research and
      theory that has accumulated can help clinicians accurately diagnose,
      conceptualize, and treat the patient's symptomatology. In this paper, the authors
      provide comprehensive review of the diagnostic criteria, epidemiology,
      differential diagnosis, and relation to chronic pain.

PMID- 21882978
TI  - Ensuring patient access to essential medicines while minimizing harmful use: a
      revised World Health Organization tool to improve national drug control policy.
AB  - In 2011, the World Health Organization (WHO) published a series of 21 guidelines
      to assist governments in improving their national drug control laws, regulations,
      and administrative procedures to promote the availability of controlled medicines
      for pain relief and for a variety of acute and chronic diseases and conditions.
      These guidelines ultimately are designed to encourage the development of policies
      designed to fulfill a country's dual obligation concerning these medicines: to
      prevent their abuse, diversion and trafficking while ensuring access for medical
      and scientific purposes. This article summarizes each guideline and outlines the
      constituents who can actively participate in making controlled medicines
      available to the patients who need them. It is hoped that representatives of
      governments and medical institutions, as well as health care professionals, will
      commonly and effectively use the revised WHO guidelines as a policy change tool.

PMID- 21882979
TI  - Breakthrough cancer pain: mending the break in the continuum of care.
AB  - On February 23, 2010, the American Pain Foundation (APF), a nonprofit
      organization that promotes pain research and increased investments in pain
      research, hosted a roundtable discussion at Beth Israel Medical Center on cancer
      related pain, with a specific focus on breakthrough cancer pain. This report
      summarizes discussions from that meeting, including recommendations and areas of
      consensus.

PMID- 21882980
TI  - Methodological challenges of comparative effectiveness research in pain:
      implications for investigators, clinicians, and policy makers.
AB  - The prevalence and costs of pain in the United States and throughout the world
      are high. This demonstrates the importance and need for comparative effectiveness
      research in pain. Comparative effectiveness research has been defined by the
      Institute of Medicine as evidence that compares the benefits and harms of
      treatment alternatives. Decision makers and consumers alike need comparative
      effectiveness data to aid in the decision making process. However, comparative
      effectiveness research presents many challenges and, in pain, has primarily been
      conducted in randomized controlled trials. These trials have some limitations
      that may prevent the application to the general population. Real world studies
      complement the information from randomized trials, but contain their own
      challenges and limitations. The International Society of Pharmacoeconomics and
      Outcomes Research has provided guidelines for the use of real world studies in
      comparative effectiveness research. The purpose of this article is to describe
      and address some the key methodological challenges of comparative effectiveness
      research, especially in pain.

PMID- 21882983
TI  - FDA acts to reduce harm from opioid drugs.

PMID- 21882985
TI  - The latest ASA mandate: CO(2) monitoring for moderate and deep sedation.

PMID- 21882986
TI  - Analysis of oxygen saturations recorded during dental intravenous sedations: a
      retrospective quality assurance of 3500 cases.
AB  - The death of a patient under sedation in New South Wales, Australia, in 2002 has
      again raised the question of the safety of dental sedation. This study sought
      answers to 2 questions: Can safe oxygen saturation levels (>= 94%) be
      consistently maintained by a single operator/sedationist? Does the additional use
      of propofol, in subanesthetic doses, increase the risk of exposure to hypoxemia?
      Three thousand five hundred cases generated between 1996 and 2006 were randomly
      examined and divided into 2 subcohorts: 1750 patients were sedated with midazolam
      and fentanyl, and 1750 patients received propofol, in subanesthetic increments,
      in addition to midazolam and fentanyl. Initial sedation was established using
      midazolam and fentanyl in both subcohorts. The second subcohort received propofol
      during times of noxious stimulation. Patient exposure to 2 or more oxygen
      desaturations below 94% was uncommon. The variables that were significantly
      associated with low saturations were age, gender, and weight. Neither the dose of
      midazolam nor the additional use of propofol was a significant risk factor. ASA
      classification (I or II) was not a determinant of risk. The data, within the
      limitations of the study, showed that a single operator/sedationist, supported by
      a well-trained team of nurses, can consistently maintain safe oxygen saturation
      levels. The additional use of propofol did not increase exposure to hypoxemia.

PMID- 21882987
TI  - Nasal foreign body: an unexpected discovery.
AB  - Abstract Nasal foreign bodies may result from the abundant availability of tiny
      objects in our society and a curious child exploring his or her nasal cavities.
      An inserted object that is not witnessed or retrieved can remain relatively
      asymptomatic or cause local tissue damage and potentially yield more serious
      consequences. An unusual case of a young child who presented for dental
      rehabilitation under general anesthesia is described. Immediately prior to the
      nasotracheal intubation, an unanticipated foreign body was detected and safely
      removed before any injury occurred. This case report discusses the presentation
      and pathophysiology of nasal foreign bodies. Moreover, applicable suggestions are
      provided to aid in the prevention and management of the unexpected discovery of a
      nasal foreign body after the induction of general anesthesia.

PMID- 21882988
TI  - Modified i-gel airway for oral surgery.

PMID- 21882989
TI  - Recognition and management of complications during moderate and deep sedation.
      Part 2: cardiovascular considerations.
AB  - The risk for cardiovascular complications while providing any level of sedation
      or general anesthesia is greatest when caring for patients already medically
      compromised. It is reassuring that significant untoward events can generally be
      prevented by careful preoperative assessment, along with attentive intraoperative
      monitoring and support. Nevertheless, providers must be prepared to manage
      untoward events should they arise. This continuing education article will review
      cardiovascular complications and address their appropriate management.

PMID- 21882992
TI  - Affinity chromatography: a valuable strategy to isolate substrates of methionine
      sulfoxide reductases?
AB  - Reactive oxygen species fulfill key roles in development and signaling, but lead
      at high concentration to damage in macromolecules. In proteins, methionine (Met)
      is particularly prone to oxidative modification and can be oxidized into Met
      sulfoxide (MetO). MetO reduction is catalyzed by specialized enzymes, termed
      methionine sulfoxide reductases (MSRs), involved in senescence and protection
      against diseases and environmental constraints. The precise physiological
      functions of MSRs remain often elusive because of very poor knowledge of their
      substrates. In this study, affinity chromatography was used to isolate partners
      of Arabidopsis thaliana plastidial methionine sulfoxide reductase B1 (MSRB1).
      Twenty-four proteins involved in photosynthesis, translation, and protection
      against oxidative stress, as well as in metabolism of sugars and amino acids,
      were identified. Statistical analysis shows that the abundance of MSRB1 partners
      in chromatography affinity samples is proportional to Met content. All proteins,
      for which structural modeling was feasible, display surface-exposed Met and are
      thus potentially susceptible to oxidation. Biochemical analyses demonstrated that
      H(2)O(2) treatment actually converts several MSRB1-interacting proteins into MSRB
      substrates. In consequence, we propose that affinity chromatography constitutes
      an efficient tool to isolate physiological targets of MSRs.

PMID- 21882993
TI  - Single-incision laparoscopy: training, techniques, and safe introduction to
      clinical practice.
AB  - BACKGROUND: Single-incision laparoscopy is an emerging technique that brings new
      challenges to laparoscopy and introduces new skills that a surgeon must learn.
      The learning needs for single-incision skills acquisition are unknown and no
      current guidelines exist for training or for its safe adoption. METHODS: We
      developed an approach to adoption of new surgical techniques and applied it to
      single-incision laparoscopy. It is based on the following principles: a defined
      training algorithm, dry and wet-laboratory practice, a graded clinical
      introduction, and careful review of early outcomes. We analyzed its impact in our
      initial 40 patients. RESULTS: Our training paradigm consisted of the following:
      attending a formal course, developing a simulation model, and animal laboratory
      training, followed by graduated clinical adoption. A 20% conversion rate to
      standard laparoscopy or open surgery occurred. CONCLUSION: Introducing a new
      surgical technique may not only offer potential advantages but also present
      significant risks. We developed a thoughtful approach to adoption that includes
      simulation-based training, progressive clinical adoption, and early review of
      outcomes. This approach may be applied to various new clinical applications.

PMID- 21882994
TI  - Pectus excavatum repair according to Nuss: is it safe to place a retrosternal bar
      by a transpleural approach, under thoracoscopic vision?
AB  - We present a new case of cardiac perforation during retrosternal dissection
      beginning a Nuss procedure for pectus excavatum repair in an 18-year-old boy. The
      true incidence of life-threatening complications, such as heart injuries during
      Nuss bar placement for pectus excavatum repair, as well as cardiac lacerations
      during removal of the bar, remains unknown. Many papers suggest measures to
      prevent these complications: approaching the retrosternal space through an
      additional subxiphoid short incision, lifting the sternum during bar placement,
      or placing the bar extrapleuraly. Nuss procedure is gaining more and more
      popularity due to its apparent simplicity; however, its operational complications
      should be well known and discussed to be avoided later on.

PMID- 21882995
TI  - Domestic and peer violence in secondary school among adolescents: can
      telemedicine help?
AB  - Domestic and peer violence in Macedonia is similar to other developed nations. It
      is present among adolescents and their families. A study was conducted on 664
      secondary school students throughout Macedonia. The results indicated that 11.2%
      male and 16.54% female students often face different kinds of family violence.
      Peer violence of different forms is marked as "often" in 8.04% male respondents
      and 5.63% female respondents. One of possibilities in preventing this negative
      phenomenon is the application of telemedicine. There is a growing body of
      evidence that the use of telemedicine offers a good tool for mental healthcare in
      underserved communities, and that these services are as effective as face-to-face
      work with adolescents. By building an effective telemedicine network in
      Macedonia, both victims (adolescents) and their parents could be given a chance
      to contact proper institutions for help with more confidence and less stress.

PMID- 21882996
TI  - Assessing swallowing disorders online: a pilot telerehabilitation study.
AB  - OBJECTIVE: Dysphagia (a swallowing disorder) is known to occur in numerous
      clinical populations, but unfortunately because of issues accessing speech
      pathology services, not all patients are able to receive dysphagia intervention
      and rehabilitation services in a timely manner. Existing research supports the
      use of telehealth technology for providing various aspects of speech pathology
      service; however, to date there is limited evidence to support the utilization of
      telerehabilitation in the assessment and management of dysphagia. The aim of this
      research was to provide pilot information on the basic feasibility and validity
      of conducting dysphagia assessments via telerehabilitation. MATERIALS AND
      METHODS: Ten simulated patients, actors portraying patients with a range of
      swallowing difficulties, were used rather than actual patients to minimize any
      potential patient risk from unidentified aspiration. Dysphagia was assessed
      simultaneously by a face-to-face (FTF) and telerehabilitation speech pathologist
      (T-SP). Each simulated patient was assessed using a Clinical Swallowing
      Examination (CSE) protocol that was modified to suit a telerehabilitation
      environment. The CSE was administered with the support of an assistant via an
      Internet-based videoconferencing telerehabilitation system using a bandwidth of
      128 kilobits per second. RESULTS: Results revealed high to excellent levels of
      agreement between the T-SP and the FTF-SP across all parameters of the CSE.
      Agreement for aspiration risk was excellent. CONCLUSION: The pilot data indicate
      that the current model of administering a CSE via telerehabilitation has
      potential to be a feasible and valid method for the remote assessment of
      swallowing disorders.

PMID- 21882997
TI  - The accuracy of weight reported in a web-based obesity treatment program.
AB  - OBJECTIVE: The overall goal of the study was to understand the accuracy of self
      reported weight over a 6-month Web-based obesity program. MATERIALS AND METHODS:
      As part of a larger study, subjects (n=323; 93% female; 28% African American)
      were randomized to a 6-month Internet-based behavioral weight loss program with
      weekly group meetings delivered either: (1) entirely by online synchronous chats
      or (2) by a combination of online chats plus monthly in-person group sessions.
      Observed weights were obtained at 0 and 6 months for all participants. Self
      reported weights were submitted weekly to the study Web site. Differences in
      Observed and Reported weights were examined by gender, race, and condition.
      RESULTS: Observed and Reported weight were significantly correlated at 0 and 6
      months (r=0.996 and 0.996, ps <0.001 respectively). However, Reported weight
      underestimated Observed weight by 0.86 kg (p<0.001) at 6 months. Further, there
      was a significant weight loss effect (p<0.001) with those losing more weight more
      accurately estimating their Reported weight at 6 months. Additionally, 6-month
      Reported weight change differed from Observed weight change (difference=0.72 kg,
      p<0.001), with weight change using Reported weights estimating a slightly larger
      weight loss than Observed weights. CONCLUSIONS: In general, the accuracy of self
      reported weight is high for individuals participating in an Internet-based weight
      loss treatment program. Accuracy differed slightly by amount of weight lost and
      was not improved with periodic in-person assessment. Importantly, weight change
      by self-report was comparable to observed, suggesting that it is suitable for Web
      based obesity treatment.

PMID- 21882998
TI  - One-year efficacy and safety of the telehealth system in poorly controlled type 2
      diabetic patients receiving insulin therapy.
AB  - OBJECTIVE: To evaluate the functionality of the telehealth system in poorly
      controlled type 2 diabetic (T2D) patients receiving insulin injections. MATERIALS
      AND METHODS: Sixty-four patients with glycosylated hemoglobin (HbA(1c)) values >
      7% for more than 1 year were included. All patients underwent an intensive
      diabetes management program, including titration of insulin, blood glucose-self
      monitoring, and nutritional review, and 32 participated in the telehealth system.
      The major outcome was to evaluate the change of the HbA(1c) and body weight, the
      incidence of hospitalization, and hypoglycemic events. RESULTS: After 1-year
      management, patients receiving telehealth care had significantly improved HbA(1c)
      levels (9.5% +/- 1.8% to 8.1% +/- 1.2%; p < 0.01) without significant body weight
      gain. In contrast, the control group patients had no significant improvement in
      HbA(1c) levels but showed significant increase in body weight (66.8 +/- 9.8 to
      67.3 +/- 10.0 kg; p < 0.01). No patient in the telehealth group was hospitalized
      during the follow-up period, but six patients in the control group were.
      Intergroup differences in hypoglycemic events were absent. CONCLUSION: The
      intensive diabetes management program with the telehealth system is a useful
      education method to improve blood sugar control and prevent hospitalization in
      poorly controlled T2D patients receiving insulin injections.

PMID- 21882999
TI  - Effects of modafinil on sleep-wake cycles in larval zebrafish.
AB  - We describe, for the first time, the effects of the wakefulness-promoting drug
      modafinil on sleep and wakefulness in larval zebrafish. Modafinil is currently
      used to treat narcolepsy, hypersomnia, and shift-work disorder by increasing
      wakefulness. Tolerance and dependence are limited with modafinil use,
      differentiating it from common stimulants; however, the neural mechanisms of
      action of modafinil are still unknown. Zebrafish, a low-cost, prolific, and
      genetically tractable animal model, have recently become a key model in sleep
      research. Zebrafish express circadian rhythms, sleep homeostasis, and sleep
      pressure, and, in addition, respond to common hypnotics and stimulants in a
      manner similar to mammals. Therefore, in the current experiment we characterize
      the effects of modafinil on sleep-wake cycles in larval zebrafish as a first step
      to gaining further insight into the neural mechanisms underlying the effects of
      modafinil. We show that modafinil modulates sleep-wake activity in larval
      zebrafish in a manner consistent with what would be predicted from mammalian
      data. Modafinil increases wakefulness by lengthening wake-bouts, an effect that
      likely restricted to the night (lights-off). These results validate the use of
      zebrafish as an animal model for the study of sleep and provide a means for
      dissecting the neural mechanisms of modafinil, and, more broadly, sleep
      disorders.

PMID- 21883001
TI  - Protective effects of Haematococcus astaxanthin on oxidative stress in healthy
      smokers.
AB  - Free radicals induced by cigarette smoking have been strongly linked to increased
      oxidative stress in vivo, contributing to the pathobiology of various diseases.
      This study was performed to investigate the effects of Haematococcus astaxanthin
      (ASX), which has been known to be a potent antioxidant, on oxidative stress in
      smokers. Thirty-nine heavy smokers (>=20 cigarettes/day) and 39 non-smokers were
      enrolled in this study. Smokers were randomly divided into three dosage groups to
      receive ASX at doses of 5, 20, or 40 mg (n=13, each) once daily for 3 weeks.
      Oxidative stress biomarkers such as malondialdehyde, isoprostane, superoxide
      dismutase, and total antioxidant capacity, and ASX levels in plasma were measured
      at baseline and after 1, 2, and 3 weeks of treatment. Compared with baseline, the
      plasma malondialdehyde and isoprostane levels decreased, whereas superoxide
      dismutase level and total antioxidant capacity increased in all ASX intervention
      groups over the 3-week period. In particular, isoprostane levels showed a
      significant dose-dependent decrease after ASX intake. The results suggest that
      ASX supplementation might prevent oxidative damage in smokers by suppressing
      lipid peroxidation and stimulating the activity of the antioxidant system in
      smokers.

PMID- 21883000
TI  - Production of F1 offspring with vitrified sperm from a live-bearing fish, the
      green swordtail Xiphophorus hellerii.
AB  - This study reports the first production of offspring with vitrified sperm from a
      live-bearing fish Xiphophorus hellerii. The overall goal of this study was to
      develop streamlined protocols for integration into a standardized approach for
      vitrification of aquatic species germplasm. The objectives were to (1) estimate
      acute toxicity of cryoprotectants, (2) evaluate vitrification solutions, (3)
      compare different thawing methods, (4) evaluate membrane integrity of post-thaw
      sperm vitrified in different cryoprotectants, and (5) evaluate the fertility of
      vitrified sperm. Nine cryoprotectants and two commercial vitrification additives
      were tested for acute toxicity and glass forming ability, alone and in
      combination. Two vitrification solutions, 40% glycerol (Gly) and 20% Gly+20%
      ethylene glycol (EG) in 500 mOsmol/kg Hanks' balanced salt solution (HBSS), were
      selected for vitrification of 10 MUL sperm samples using inoculating loops
      plunged into liquid nitrogen. Samples were thawed at 24 degrees C (one loop in 5
      MUL of HBSS or three loops in 500 MUL of HBSS). Samples thawed in 500 MUL were
      concentrated by centrifugation (1000 g for 5 min at 4 degrees C) into 5 MUL for
      artificial insemination. Offspring were produced from virgin females inseminated
      with sperm vitrified with 20% Gly+20% EG and concentrated by centrifugation.

PMID- 21883002
TI  - Citrus grandis peel increases the bioavailability of cyclosporine and tacrolimus,
      two important immunosuppressants, in rats.
AB  - Citrus grandis peel (CGP) is a beverage ingredient and a medicinal herb in
      Oriental countries. Cyclosporine and tacrolimus, important immunosuppressants
      with narrow therapeutic windows, are widely used in transplant patients. This
      study investigated the effects of co-administering CGP on the bioavailability of
      cyclosporine and tacrolimus. Male Sprague-Dawley rats were orally administered
      tacrolimus or cyclosporine with and without CGP. The concentrations of
      cyclosporine and tacrolimus in blood were assayed by monoclonal fluorescence
      polarization immunoassay and microparticle enzyme immunoassay, respectively. P
      glycoprotein- and cytochrome P 450 3A4 (CYP3A4)-associated mechanisms were
      investigated by using everted rat intestinal sac and recombinant CYP3A4 isozyme.
      The results showed that CGP significantly increased the bioavailability of
      cyclosporine and tacrolimus by 100.0% and 234.7%, respectively. Ex vivo studies
      indicated that the interaction was mediated by the inhibition of CYP3A4. We
      suggest that CGP is contraindicated for transplant patients treated with
      cyclosporine or tacrolimus to minimize the risk of intoxication.

PMID- 21883003
TI  - (-)-epigallocatechin-3-O-gallate augments pentobarbital-induced sleeping
      behaviors through Cl- channel activation.
AB  - This experiment investigated whether (-)-epigallocatechin-3-O-gallate (EGCG) (5
      20 mg/kg, p.o.) has hypnotic effects and/or enhances pentobarbital-induced
      sleeping behaviors and whether these effects are mediated by gamma-aminobutyric
      acid (GABA) receptors. EGCG prolonged sleeping time induced by pentobarbital (42
      mg/kg, i.p.) and reduced sleeping latency induced by pentobarbital similarly to
      muscimol (0.2 mg/kg, i.p.), a GABA(A) receptor agonist in mice. EGCG also
      increased sleeping rate and sleeping time when co-administered with pentobarbital
      (28 mg/kg, i.p.) at a subhypnotic dosage. In addition, EGCG and pentobarbital
      increased chloride (Cl(-)) influx in primary cultured cerebellar cells. EGCG and
      pentobarbital decreased GABA(A) receptors alpha-subunit expression and had no
      effect on the expression of beta- and gamma-subunits and of glutamic acid
      decarboxylase in the hippocampus of rats. In conclusion, the EGCG enhancement of
      Cl(-) influx may play an important role in pentobarbital-induced sleeping
      behaviors.

PMID- 21883004
TI  - Caffeine increases sweating sensitivity via changes in sudomotor activity during
      physical loading.
AB  - We assessed the effect of caffeine on sudomotor activity and sweating sensitivity
      during physical loading. Both physiological responses could occur due to energy
      expenditure. Subjects were 13 athletically trained males (22.1 +/- 3.7 years old,
      174.2 +/- 5.4 cm tall, and weighing 70.9 +/- 4.6 kg, with maximal oxygen
      consumption [VO(2)max] of 53.6 +/- 4.4 mL/kg/minute). The study involved a within
      subject, random, crossover design. Tests were performed following the ingestion
      of 3 mg/kg caffeine. The physical loading involved running for 30 minutes at 60%
      VO(2)max (24.0 +/- 0.5 degrees C, 40 +/- 3.0% relative humidity). Tympanic
      temperature (TYMP) was significantly higher in the caffeine-consuming group
      (Caffe-I) at pre-exercise (40 minutes after caffeine intake and immediately
      before running) (P<.05). Mean body temperature (mT(b)) was significantly higher
      in the Caffe-I group at pre- and post-exercise (30 min after start of running)
      (P<.05). Onset time of localized sweating was significantly shorter in the Caffe
      I group (P<.01), but localized sweat volume and active sweat gland output (per
      single gland) was significantly higher in the Caffe-I group (P<.001). Activated
      sweat gland density was significantly increased in the Caffe-I group on the
      abdomen and thigh (P<.01). In conclusion, caffeine ingestion caused not only
      increases in TYMP and mT(b) through thermogenesis, but also an increased sweating
      sensitivity via changes in sudomotor activity.

PMID- 21883005
TI  - Characterization of bla(CMY)-encoding plasmids among Salmonella isolated in the
      United States in 2007.
AB  - Salmonella enterica is one of the most common bacterial causes of foodborne
      illness, and nontyphoidal Salmonella is estimated to cause ~1.2 million illnesses
      in the United States each year. Plasmids are mobile genetic elements that play a
      critical role in the dissemination of antimicrobial resistance determinants. AmpC
      type CMY beta-lactamases (bla(CMY)) confer resistance to extended-spectrum
      cephalosporins and beta-lactam/beta-lactamase inhibitor combinations and are
      commonly plasmid-encoded. A variety of plasmids have been shown to encode CMY
      beta-lactamases and certain plasmids may be associated with particular Salmonella
      serotypes or environmental sources. In this study, we characterized bla(CMY) beta
      lactamase-encoding plasmids among Salmonella isolates. Isolates of Salmonella
      from specimens collected from humans in 2007 were submitted to the Centers for
      Disease Control and Prevention National Antimicrobial Resistance Monitoring
      System laboratory for susceptibility testing. Three percent (65/2161) of
      Salmonella isolates displayed resistance to ceftriaxone (minimum inhibitory
      concentration [MIC] >=4 mg/L) and amoxicillin/clavulanic acid (MIC >=32 mg/L), a
      combination associated with the presence of a bla(CMY) mechanism of resistance.
      Sixty-four (98.5%) isolates were polymerase chain reaction-positive for bla(CMY)
      genes. Transformation and conjugation studies showed that 95% (61/64) of the
      bla(CMY) genes were plasmid-encoded. Most of the bla(CMY)-positive isolates were
      serotype Typhimurium, Newport, Heidelberg, and Agona. Forty-three plasmids were
      replicon type IncA/C, 15 IncI1, 2 contained multiple replicon loci, and 1 was
      untypeable. IncI1 plasmids conferred only the bla(CMY)-associated resistance
      phenotype, whereas IncA/C plasmids conferred additional multi-drug resistance
      (MDR) phenotypes to drugs such as chloramphenicol, sulfisoxazole, and
      tetracycline. Most of the IncI1 plasmids (12/15) were sequence type 12 by plasmid
      multi-locus sequence typing. CMY beta-lactamase-encoding plasmids among human
      isolates of Salmonella in the United States tended to be large MDR IncA/C
      plasmids or single resistance determinant IncI1 plasmids. In general, IncI1
      plasmids were identified among serotypes commonly associated with poultry,
      whereas IncA/C plasmids were more likely to be identified among cattle/beef
      associated serotypes.

PMID- 21883006
TI  - Vibrio parahaemolyticus isolates from southeastern Chinese coast are genetically
      diverse with circulation of clonal complex 3 strains since 2002.
AB  - Multilocus sequence typing (MLST) was used to examine the clonal relationship and
      genetic diversity of 71 Vibrio parahaemolyticus isolates from clinical and
      seafood-related sources in southeastern Chinese coast between 2002 and 2009. The
      tested isolates fell into 61 sequence types (STs). Of 17 clinical isolates, 7
      belonged to ST3 of the pandemic clonal complex 3, with 3 strains isolated in
      2002. Although there was no apparent clonal relationship found between clinical
      strains and those from seafood-related sources positive with pathogenic markers,
      there were clonal relationships between clinical strains from this study and
      those from environmental sources in other parts of China. Phylogenetic analysis
      showed that strains of 112 STs (61 STs from this study and 51 retrieved from
      PUBMLST database covering different continents) could be divided into four
      branches. The vast majority of our isolates and those from other countries were
      genetically diverse and clustered into two major branches of mixed distribution
      (of geographic origins and sample sources), whereas five STs representing six
      isolates split as two minor branches because of divergence of their recA genes,
      which had 80%-82% nucleotide identity to typical V. parahaemolyticus strains and
      73.3%-76.9% identity to the CDS24 of a Vibrio sp. plasmid p23023, indicating that
      the recA gene might have recombined by lateral gene transfer. This was further
      supported by a high ratio of recombination to mutation (3.038) for recA. In
      conclusion, MLST with fully extractable database is a powerful system for
      analysis of clonal relationship for strains of a particular region in a national
      or global scale as well as between clinical and environmental or food-related
      strains.

PMID- 21883007
TI  - Association between antimicrobial resistance in Escherichia coli isolates from
      food animals and blood stream isolates from humans in Europe: an ecological
      study.
AB  - BACKGROUND: In addition to medical antimicrobial usage, the use of antimicrobials
      in food animals contributes to the occurrence of resistance among some bacterial
      species isolated from infections in humans. Recently, several studies have
      indicated that a large proportion of Escherichia coli causing infections in
      humans, especially those resistant to antimicrobials, have an animal origin.
      METHODS: We analyzed the correlation between the prevalence of antimicrobial
      resistance in E. coli isolates from blood stream infections in humans and in E.
      coli isolates from poultry, pigs, and cattle between 2005 and 2008 for 11
      countries, using available surveillance data. We also assessed the correlation
      between human antimicrobial usage and the occurrence of resistance in E. coli
      isolates from blood stream infections. RESULTS: Strong and significant
      correlations between prevalences of resistance to ampicillin (r=0.94),
      aminoglycosides (r=0.72), third-generation cephalosporins (r=0.76), and
      fluoroquinolones (r=0.68) were observed for human and poultry E. coli isolates.
      Similar significant correlations were observed for ampicillin (r=0.91),
      aminoglycosides (r=0.73), and fluoroquinolone resistance (r=0.74) in pig and
      human isolates. In cattle isolates, only ampicillin resistance (r=0.72) was
      significantly correlated to human isolates. When usage of antimicrobials in
      humans was analyzed with antimicrobial resistance among human isolates, only
      correlations between fluoroquinolones (r=0.90) and third-generation
      cephalosporins (r=0.75) were significant. CONCLUSIONS: Resistance in E. coli
      isolates from food animals (especially poultry and pigs) was highly correlated
      with resistance in isolates from humans. This supports the hypothesis that a
      large proportion of resistant E. coli isolates causing blood stream infections in
      people may be derived from food sources.

PMID- 21883008
TI  - A retrospective analysis of primary diagnosis, comorbidities, anticholinergic
      load, and other factors on treatment for noisy respiratory secretions at the end
      of life.
AB  - BACKGROUND: Noisy respiratory secretions (NRS) at the end of life have been
      described in 23%-92% of deaths in palliative care units. Despite limited evidence
      to support the efficacy of the antisecretory medications, hyoscine hydrobromide
      and glycopyrrolate, administration of these medications remains standard
      palliation. Predicting those at risk of NRS could allow early and targeted
      intervention. METHODS: A retrospective analysis of 199 deaths in a palliative
      care unit was undertaken to identify if any patient, disease, or treatment
      related factors might be predictive or protective of the symptom. RESULTS: In the
      last 72 hours of life, 60% received antisecretory medication (mean, 2; range, 0
      16 doses). Significant unadjusted associations were found between administration
      of antisecretory medications and survival as well as the anticholinergic drug
      load from other medications. Results obtained from logistic regressions revealed
      patients with a higher anticholinergic load from prescribed medications were more
      likely to require treatment for NRS (odds ratio [OR]=2.9, 95% confidence interval
      [CI]=1.4-5.7). There were no other factors significantly associated with
      developing the symptom. CONCLUSION: A high anticholinergic load from medications
      was not protective and instead predicted the need for treatment for NRS at the
      end of life.

PMID- 21883010
TI  - Urolithiasis location and size and the association with microhematuria and stone
      related symptoms.
AB  - PURPOSE: To conduct a study to assess the association between calculus location
      and size and the incidence of both microhematuria and symptoms of urolithiasis in
      a urology office environment. PATIENTS AND METHODS: After Institutional Review
      Board approval, a prospective study was conducted with data from 100 consecutive
      patients who presented to our office with documented urolithiasis. The location
      (caliceal, pelvic, or ureteral) and size (<or >= 8 mm) of each calculus was
      determined from available diagnostic radiographs. The incidence of microhematuria
      was ascertained via a urine dipstick and microscopic examination. The presence of
      any symptoms associated with urolithiasis, including pain, subjective fever or
      chills, or urinary urgency, was recorded. RESULTS: A total of 111 stones were
      found in the study population resulting in a 45.9% incidence of microhematuria.
      In patients with renal pelvic and ureteral stones, 67.6% demonstrated
      microhematuria vs 36.4% with caliceal stones, P=0.0035. For stones >= 8 mm, 62.5%
      were positive for microhematuria vs 29.1% of stones <8 mm, P=0.0006. Ureteral or
      renal pelvic stones caused the most symptoms (70.6%) compared with caliceal
      stones (16.9%), P=0.0001. In those patients who reported pain associated with
      urolithiasis, 65.6% had concomitant microhematuria vs 36.8% in those without
      pain, P=0.0097. CONCLUSIONS: Urinary calculus location and size are associated
      with the incidence of microhematuria and stone-related symptoms. Pain related to
      urolithiasis may be a positive predictor for the presence of microhematuria.

PMID- 21883009
TI  - Plasma citrate levels as a potential biomarker for glaucoma.
AB  - PURPOSE: To determine the possibility of plasma citrate as a biomarker in
      patients with glaucoma. METHODS: Twenty-one consecutive Caucasian patients with
      glaucoma and 21 sex- and age-matched controls were investigated. Plasma citrate,
      plasma creatinine, urine citrate, and urine creatinine were analyzed by ion
      chromatography. Mean (+/-standard deviation) concentrations and the calculated
      fractional citrate excretions were compared using the Mann-Whitney test.
      Sensitivity and specificity to detect glaucoma using plasma citrate levels were
      calculated. RESULTS: The mean plasma citrate (104.8+/-23.2 vs. 128.2+/-31.1
      MUmol/L; P=0.01) concentrations were significantly lower among the patients with
      glaucoma, whereas the mean urine citrate concentrations (1.7+/-0.9 vs. 2.8+/-1.9
      MUmol/L; P=0.07) were slightly lower. Mean plasma and mean urine creatinine
      concentrations showed no significant differences (plasma creatinine: 63.0+/-16.7
      vs. 63.4+/-15.5 MUmol/L; P=0.72; urine creatinine: 9.6+/-5.1 vs. 11.5+/-8.4
      MUmol/L; P=0.67). The calculated fractional citrate excretions were also not
      different with 12.1% versus 13.6% (P=0.37). Setting the cut-off limit at 110
      MUmol/L, the plasma citrate level evaluation would have a sensitivity of 66.7%
      and a specificity of 71.4% to detect glaucoma. CONCLUSION: In this masked study,
      plasma citrate levels were significantly decreased in Caucasian patients with
      glaucoma giving the possibility to use them eventually as a biomarker. The kidney
      function was normal in both groups, leaving the etiology of this hypocitraemia
      yet unexplained.

PMID- 21883011
TI  - Correlation between stress and kidney stone disease.
AB  - BACKGROUND AND PURPOSE: Prevalence of kidney stone disease is increasing
      worldwide, and several factors may be involved. We aimed to establish a
      correlation between stress and kidney stones. PATIENTS AND METHODS: We
      prospectively evaluated 200 patients with a diagnosis of kidney stone disease
      having them self-respond to a validated questionnaire to measure stress
      (Perceived Stress Scale-10 [PSS-10]). Stone-related characteristics and potential
      stressing factors were assessed. Variables that were significant on the
      univariate analysis were used to construct a model that was able to explain the
      variability in PSS-10 score in our patients. RESULTS: Mean PSS-10 score was 15.3
      +/- 1.1. Female sex (P=0.014), occurrence of death or serious illness of a family
      member or close friend within the last 6 months of the interview (P=0.044),
      occurrence of other psychological trauma (P<0.0001) all proved to be significant
      factors. Stone-related aspects associated with stress were presence of symptoms
      at the time of the interview (P=0.012) and passage of two or more stones per year
      (P=0.022). We were able to construct a model that explains 34% of the variability
      of the PSS-10 between subjects. Employment status was the only significant
      variable, but sex, age, and presence of symptoms at the time of questionnaire
      administration had to be kept in to achieve a model that explains the largest
      variability. CONCLUSIONS: Passage of two or more stones per year and presence of
      symptoms proved to be factors related to elevated stress in patients with a
      diagnosis of kidney stone disease. Female sex, age, and unemployment may also
      contribute to a stressed state in this population.

PMID- 21883012
TI  - Continuous-wave laser stimulation of the rat prostate cavernous nerves using a
      compact and inexpensive all single mode optical fiber system.
AB  - BACKGROUND AND PURPOSE: Laser stimulation of the rat cavernous nerve (CN)
      recently has been demonstrated as an alternative to electrical stimulation for
      potential application in nerve mapping during nerve-sparing radical
      prostatectomy. Advantages include noncontact stimulation and improved spatial
      selectivity. Previous studies, however, have used large and/or expensive laser
      sources for stimulation. This study demonstrates the feasibility of optical
      stimulation of the rat CN, in vivo, using a compact, inexpensive all-single-mode
      fiberoptic system. MATERIALS AND METHODS: A 1455-nm wavelength infrared diode
      laser beam was coupled into a 9-MUm-core single-mode fiber for delivery through a
      10F laparoscopic probe and used for laser stimulation of the CN in a total of
      eight rats, in vivo. RESULTS: Laser stimulation of the CN was observed at
      threshold temperatures of 41 degrees C, with intracavernous pressure response
      times as short as 4 s, and magnitudes up to 50 mm Hg, compared with baselines of
      10 mm Hg. CONCLUSION: This novel, all-single-mode-fiber laser nerve stimulation
      system introduces several advantages including: (1) lower cost laser; (2) more
      robust fiberoptic design, eliminating alignment and cleaning of bulk optical
      components; and (3) improved Gaussian spatial beam profile for simplified
      alignment of the laser beam with the nerve. With further development, laser nerve
      stimulation may be useful for identification and preservation of the CN during
      prostate cancer surgery.

PMID- 21883013
TI  - [99mTc]demotensin VI: biodistribution and initial clinical results in tumor
      patients of a pilot/phase I study.
AB  - PURPOSE: Neurotensin subtype 1 receptor overexpression is found in a variety of
      human tumors. The aim of this pilot/phase I study was to assess the safety
      profile, pharmacokinetics, and imaging characteristics of (99m)Tc-Demotensin VI
      in tumor patients. METHODS: Scintigraphy with (99m)Tc-Demotensin VI was performed
      in 14 patients (2 female and 12 male) with advanced tumor stages. The diagnoses
      were pancreatic adenocarcinoma (n=4), small cell lung cancer (SCLC) (n=4), non
      small cell lung cancer (NSCLC) (n=4), and colon carcinoma (n=2). Patients were
      injected with 500-550 MBq (99m)Tc-Demotensin VI. Blood samples were taken at
      various time points and urine was also collected up to 24 hours post-injection
      (p.i.) Planar images were acquired at 15-30 minutes, 1-2 hours, 4 hours, and 24
      hours p.i. with additional SPECT imaging at 4 hours. RESULTS: Radiochemical
      purity always exceeded 95% up to 4 hours. Urinary and blood excretion was rapid
      with 5.05% ID (mean: n=5) in plasma after 4 hours. No side effects were observed
      after injection of (99m)Tc-Demotensin VI. Focal tracer accumulation was observed
      in 3 patients with brain metastases due to NSCLC, although specificity of this
      uptake could not be proven. Further, no tumor-related findings were observed.
      Although stability tests in human plasma revealed that (99m)Tc-Demotensin VI
      remained intact up to 2 hours incubation, ex vivo urine analysis indicated rapid
      metabolism. CONCLUSION: (99m)Tc-Demotensin VI was well tolerated by patients and
      showed favorable pharmacokinetics; however, tumor targeting was limited to brain
      metastases. Further studies on stability issues and receptor characterization in
      tumors are warranted to introduce neurotensin receptors (NTSR) imaging into the
      clinic.

PMID- 21883014
TI  - Synthesis and preliminary bioevaluation of 99mTc(CO)3-17alpha-triazolylandrost-4
      ene-3-one derivative prepared via click chemistry route.
AB  - Azolyl steroids are known to manifest antiprostate cancer and antiandrogenic
      activities. These azolyl steroids have been shown to express affinity toward
      androgen receptors (ARs) overexpressed on LNCaP (human prostate adenocarcinoma)
      cell line. Hence, suitably derivatized azolyl steroids can be envisaged as
      potential vectors for targeting overexpression of ARs in prostate cancer. In the
      present study, testosterone has been derivatized to 17alpha-azidoandrost-4-ene-3
      one using microwave-mediated azidation of the mesylate. Subsequently, a facile
      one-pot Cu(I)-catalyzed Click reaction was carried out to synthesize
      (99m)Tc(CO)(3)-labeled 17alpha-triazolylandrost-4-ene-3-one, which was
      characterized by HPLC. The chemical characterization of (99m)Tc(CO)(3)-17alpha
      triazolylandrost-4-ene-3-one was carried out by preparing its corresponding
      rhenium complex using [NEt(4)](2)[Re(CO)(3)Br(3)] precursor. The radiolabeled
      complex could be prepared in >95% radiochemical yield as determined by HPLC. In
      vitro studies of (99m)Tc(CO)(3)-17alpha-triazolylandrost-4-ene-3-one complex in
      LNCaP cell lines overexpressing ARs showed binding of 4.95%+/-1.2%, with
      inhibition of 8%+/-0.9%. In vivo biodistribution studies in male Wistar rats have
      shown uptake in the prostate to the extent of 0.48%+/-0.19% injected dose/g at 1
      hpi and retention therein till 3 hpi. The present study demonstrates a novel and
      facile one-pot reaction for preparation of (99m)Tc-labeled 17alpha
      triazolylandrost-4-ene-3-one complex using Click chemistry. The corresponding Re
      analog has been prepared for purpose of comparative characterization with the
      (99m)Tc-labeled complex. The radiosynthetic strategy described in this article
      can be further extended toward preparation of radiolabeled complexes of other
      triazolyl steroidal derivatives.

PMID- 21883015
TI  - Role of inhibitor of apoptosis protein Livin in radiation resistance in nonsmall
      cell lung cancer.
AB  - OBJECTIVE: The objective of the present study was to explore the role of the
      inhibitor of apoptosis protein (IAP) Livin in radioresistance in nonsmall cell
      lung cancer (NSCLC). METHODS: Lung adenocarcinoma cell lines A549 and SPC-A1 were
      used for this study. Using the technique of molecular cloning and gene
      transfection, two Livin isoforms, Livinalpha and beta, respectively, were
      expressed in A549 cells with the purpose of exploring the role of Livin in
      radiation resistance of A549 cells. Moreover, a Livin-specific gene-silencing
      system was developed using SPC-A1 cell line with the purpose of increasing
      radiosensitivity of SPC-A1 cells. RESULTS: A549 cells were induced by radiation
      to express Livin isoforms, Livinalpha and beta. A549 cells expressed Livin
      isoforms stably after gene transfection and the transfected cells demonstrated
      characteristics of antiradiation. However, Livin gene-silenced SPC-A1 cells
      exhibited remarkably enhanced radiation sensitivity. CONCLUSION: The IAP Livin is
      an important molecule in antiradiotherapy of NSCLC. Livin-specific gene silencing
      is likely to be an effective means to enhance radiation sensitivity of lung
      cancer.

PMID- 21883016
TI  - Hair follicle regeneration in skin grafts: current concepts and future
      perspectives.
AB  - The repair and management of full-thickness skin defects resulting from burns and
      chronic wounds remain a significant unmet clinical challenge. For those skin
      defects exceeding 50%-60% of total body surface area, it is impractical to treat
      with autologous skin transplants because of the shortage of donor sites. The
      possibility of using tissue-engineered skin grafts for full-thickness wound
      repair is a promising approach. The primary goal of tissue-engineered skin grafts
      is to restore lost barrier function, but regeneration of appendages, such as hair
      follicles, has to be yet achieved. The successful regeneration of hair follicles
      in immunodeficient mice suggests that creating human hair follicles in tissue
      engineered skin grafts is feasible. However, many limitations still need to be
      explored, particularly enriching isolated cells with trichogenic capacity,
      maintaining this ability during processing, and providing the cells with proper
      environmental cues. Current advances in hair follicle regeneration, in vitro and
      in vivo, are concisely summarized in this report, and key requirements to
      bioengineer a hair follicle are proposed, with emphasis on a three-dimensional
      approach.

PMID- 21883017
TI  - Yukmijihwang-tang inhibits receptor activator for nuclear Factor-kappaB ligand
      induced osteoclast differentiation.
AB  - Yukmijihwang-tang (YMT) is a traditional herbal medicine known to enhance memory
      in brain injury models. The aims of this study were to evaluate the inhibitory
      effect of YMT on osteoclast differentiation and to determine its molecular
      mechanism of action. YMT dose-dependently inhibited receptor activator for
      nuclear factor-kappaB (NF-kappaB) ligand (RANKL)-induced tartrate-resistant acid
      phosphatase (TRAP) activity and the formation of multinucleated osteoclasts in
      RAW264.7 cells. In addition, quantitative reverse transcription-polymerase chain
      reaction showed that YMT significantly decreased RANKL-induced expression of
      osteoclast differentiation-specific genes (TRAP, matrix metalloproteinase-9,
      cathepsin K, and the d2 isoform of vacuolar ATPase V(0) domain). Furthermore, YMT
      inhibited RANKL-induced phosphorylation of mitogen-activated protein kinases
      (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38),
      phosphorylation of I-kappaBalpha, phosphorylation of NF-kappaB p65, and the
      expression of transcription factors Fra-2 and nuclear factor of activated T
      cells, cytoplasmic 1. Furthermore, YMT inhibited the bone-resorptive activity of
      differentiated osteoclasts, suggesting that YMT inhibits osteoclast
      differentiation by suppressing RANKL-induced signaling molecules and
      transcription factors that affect the regulation of genes for osteoclast
      differentiation. As such, YMT may have therapeutic potential in bone diseases.

PMID- 21883019
TI  - The Edward H. Angle research prize.

PMID- 21883021
TI  - Re: Clinical outcomes for patients finished with the Sure Smile TM method
      compared with conventional fixed orthodontic therapy. Angle Orthod. 2011;81:383
      388). By Timothy J. Alford, W. Eugene Roberts, James K.Hartsfield Jr, George J.
      Eckert, Ronald J. Snyder.

PMID- 21883022
TI  - Decreasing the adverse effects of cancer therapy: an NCI Workshop on the
      preclinical development of radiation injury mitigators/protectors.

PMID- 21883023
TI  - Orthodontic movement of a maxillary incisor through the midpalatal suture: a case
      report.
AB  - Orthodontic space closure is a treatment alternative when a maxillary central
      incisor is missing. The objective of this report was to present an unusual
      treatment in which a right maxillary central incisor was moved through the
      midpalatal suture to replace the absent contralateral tooth. The biologic aspects
      and clinical appearance of the recontoured lateral and central incisors were
      analyzed. The position of the examined teeth and the appearance of the
      surrounding soft tissues were satisfactory; however, the upper midline frenulum
      deviated to the left. The incisor was successfully moved with no obvious
      detrimental effects as observed on the final radiographs. In the radiographic and
      tomographic examinations, the midline suture seemed to have followed the tooth
      movement. The patient expressed satisfaction with the results. It was concluded
      that orthodontic movement of the central incisor to replace a missing
      contralateral tooth is a valid treatment option, and the achievement of an
      esthetic result requires an interdisciplinary approach, including restorative
      dentistry and periodontics.

PMID- 21883018
TI  - Inference of subgenomic origin of BACs in an interspecific hybrid sugarcane
      cultivar by overlapping oligonucleotide hybridizations.
AB  - Sugarcane (Saccharum spp.) breeders in the early 20th century made remarkable
      progress in increasing yield and disease resistance by crossing Saccharum
      spontaneum L., a wild relative, to Saccharum officinarum L., a traditional
      cultivar. Modern sugarcane cultivars have approximately 71%-83% of their
      chromosomes originating from S. officinarum, approximately 10%-21% from S.
      spontaneum, and approximately 2%-13% recombinant or translocated chromosomes. In
      the present work, C(0)t-based cloning and sequencing (CBCS) was implemented to
      further explore highly repetitive DNA and to seek species-specific repeated DNA
      in both S. officinarum and S. spontaneum. For putatively species-specific
      sequences, overlappping oligonucleotide probes (overgos) were designed and
      hybridized to BAC filters from the interspecific hybrid sugarcane cultivar 'R570'
      to try to deduce parental origins of BAC clones. We inferred that 12 967 BACs
      putatively originated from S. officinarum and 5117 BACs from S. spontaneum.
      Another 1103 BACs were hybridized by both species-specific overgos, too many to
      account for by conventional recombination, thus suggesting ectopic recombination
      and (or) translocation of DNA elements. Constructing a low C(0)t library is
      useful to collect highly repeated DNA sequences and to search for potentially
      species-specific molecular markers, especially among recently diverged species.
      Even in the absence of repeat families that are species-specific in their
      entirety, the identification of localized variations within consensus sequences,
      coupled with the site specificity of short synthetic overgos, permits researchers
      to monitor species-specific or species-enriched variants.

PMID- 21883025
TI  - Metabolic alterations and chronic hepatitis C: treatment strategies.
AB  - INTRODUCTION: Chronic hepatitis C (HCV) infection is considered a metabolic
      disease. It is associated with a specific metabolic syndrome, HCV-associated
      dysmetabolic syndrome (HCADS), consisting of steatosis, hypocholesterolemia and
      insulin resistance/diabetes. These metabolic derangements contribute to a
      decrease in sustained virological response (SVR) to pegylated-interferon-alpha
      ribavirin as standard of care (SOC), and are associated with progression of liver
      fibrosis. AREAS COVERED: The review, highlighting the impact of HCADS and
      metabolic syndrome components of HCV disease progression and SOC, discusses
      current knowledge and perspectives on metabolic therapeutic strategies aimed at
      improving SVR rate of SOC for chronic hepatitis C. EXPERT OPINION: HCV, features
      of HCADS and of metabolic syndrome may coexist in the same patient, thus all
      components of the metabolic syndrome must be assessed to individualize treatment.
      The results of therapeutic trials evaluating metabolic strategies combined with
      current SOC indicate that weight loss is a critical part of treatment which will
      improve both disease outcome and therapeutic response to SOC. Similarly, statins
      seem to improve response rate to SOC representing, once confirmed to be safe, an
      important therapeutic tool for HCV-infected patients. Findings from studies using
      insulin sensitizers combined with SOC are not conclusive and do not justify the
      use of this class of drugs in clinical practice.

PMID- 21883026
TI  - Influence of light on aryl hydrocarbon receptor signaling and consequences in
      drug metabolism, physiology and disease.
AB  - INTRODUCTION: A key to understanding the biological function(s) of the aryl
      hydrocarbon receptor (AHR) - a xenobiotic-activated receptor - is to identify its
      endogenous ligand(s). The discovery of a tryptophan photoproduct 6
      formylindolo[3,2-b]carbazole (FICZ) as an endogenous, high affinity agonist of
      AHR filled this knowledge gap in the context of skin physiology and pathology in
      response to light and opened several new directions for research on AHR. AREA
      COVERED: This paper reviews major developments in the study of light-elicited AHR
      signaling and its impact on drug metabolism, skin physiology and disease with a
      focus on the identification of AHR ligands from Trp photoproducts and the AHR
      mediated UV response. This review consists of material obtained from Medline and
      PubMed literature searches up to May 2011. EXPERT OPINION: The recognition of
      FICZ as a potent, endogenous ligand of AHR provided a molecular link between
      light exposure and AHR signaling and function. The uncovering of the bifurcated
      signaling pathway of AHR in the mammalian UV response - that is, activation of
      the cytoplasmic AHR by light via FICZ leads to: i) AHR/AH response element
      dependent transcription to induce CYP1A1 and ii) activation of the AHR-pp60(src)
      EGFR pathway to induce Cox-2 - put forward a working model for the multiple roles
      of AHR in skin function and disease that include drug metabolism, circadian
      oscillation, melanogenesis, inflammation, immunosuppression and cancer. Such
      findings suggest AHR as a therapeutic target for cancer, autoimmune dysfunction,
      inflammatory disease and stem cell therapy.

PMID- 21883027
TI  - Pupillometry and 123I-DaTSCAN imaging in Parkinson's disease: a comparison study.
AB  - The purpose of this study was the evaluation of pupil light reflex (PLR) in
      patients with Parkinson's disease (PD) by using a modern pupillometry system and
      the investigation of its potential relationship with dopamine transporter imaging
      (DaTSCAN), which is an objective method for the evaluation of presynaptic
      dopaminergic system. PLR was evaluated using pupillometry in 35 patients with PD
      without clinical evidence of autonomic dysfunction and 44 healthy matched
      controls. PLR was elicited using a fully automated pupillometry system and six
      parameters were measured. Dopamine transporter imaging was performed using
      radioactive ioflupane (123)I-FP-CIT [(123)I-N-omega-fluoropropyl-2beta
      carbomethoxy-3beta-(4-iodophenyl)-nortropane]. A significant increase in latency
      and a significant decrease in amplitude, maximum constriction velocity, as well
      as maximum acceleration were observed in PD patients. There was no significant
      difference in initial radius and minimum radius values. Investigating the
      relationship between pupillometry parameters and (123)I-FP-CIT binding values, we
      correlated values from the semiquantitative analysis of radioligand uptake with
      pupillometry parameters, but we found no significant correlation. This study
      demonstrates PLR impairment in patients with PD without overt autonomic
      dysfunction. This impairment does not seem to correspond to the reduction of
      radioligand binding in the striatum as the result of presynaptic dopaminergic
      dysfunction, suggesting a different deterioration rate of these systems.

PMID- 21883024
TI  - Cytomegalovirus antivirals and development of improved animal models.
AB  - INTRODUCTION: Cytomegalovirus (CMV) is a ubiquitous pathogen that establishes a
      lifelong asymptomatic infection in healthy individuals. Infection of
      immunesuppressed individuals causes serious illness. Transplant and AIDS patients
      are highly susceptible to CMV leading to life-threatening end-organ disease.
      Another vulnerable population is the developing fetus in utero, where congenital
      infection can result in surviving newborns with long-term developmental problems.
      There is no vaccine licensed for CMV and current antivirals suffer from
      complications associated with prolonged treatment. These include drug toxicity
      and emergence of resistant strains. There is an obvious need for new antivirals.
      Candidate intervention strategies are tested in controlled preclinical animal
      models but species specificity of human CMV precludes the direct study of the
      virus in an animal model. AREAS COVERED: This review explores the current status
      of CMV antivirals and development of new drugs. This includes the use of animal
      models and the development of new improved models such as humanized animal CMV
      and bioluminescent imaging of virus in animals in real time. EXPERT OPINION:
      Various new CMV antivirals are in development, some with greater spectrum of
      activity against other viruses. Although the greatest need is in the setting of
      transplant patients, there remains an unmet need for a safe antiviral strategy
      against congenital CMV. This is especially important as an effective CMV vaccine
      remains an elusive goal. In this regard, greater emphasis should be placed on
      suitable preclinical animal models and greater collaboration between industry and
      academia.

PMID- 21883028
TI  - Pretransplant serum ferritin has a prognostic influence on allogeneic transplant
      regardless of disease risk.
AB  - A multicenter retrospective analysis of the influence of pretransplant serum
      ferritin (SF) was performed in 261 adult recipients of allogeneic hematopoietic
      stem cell transplant (allo-HSCT), including 159 patients with acute myeloid
      leukemia (AML), 66 with acute lymphoid leukemia (ALL) and 36 with myelodysplastic
      syndrome (MDS). Patients were divided into subgroups according to the
      pretransplant SF level [< 1000 ng/mL (low) vs. >= 1000 ng/mL (high)] and disease
      status at transplant. A high SF level was significantly associated with high
      disease risk (p = 0.041), but pretransplant SF and disease risk were independent
      significant prognostic factors for overall survival (OS), disease-free survival
      (DFS) and non-relapse mortality rate (NRM) on multivariate analysis. The high-SF
      group showed a worse outcome than the low-SF group among both standard-risk
      patients (OS: 54% vs. 64%, p = 0.043; DFS: 46% vs. 57%, p = 0.031) and high-risk
      patients (OS: 16% vs. 35%, p = 0.001; DFS: 15% vs. 34%, p = 0.001). In
      conclusion, a high SF at transplant adversely influences the outcome of allo-HSCT
      regardless of disease risk in patients with acute leukemia and MDS.

PMID- 21883029
TI  - Association between quality of life and clinical parameters in patients with
      myeloproliferative neoplasms.
AB  - The Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) is a validated
      quality of life (QoL) instrument. In our Swedish cohort of 114 patients the
      symptomatic burden was found to be severe, with fatigue reported in 88% of the
      patients and reduced QoL in the majority of patients. Patients with primary
      myelofibrosis had the highest scores, low QoL, for most MPN-SAF items, compared
      to patients with polycythemia vera and essential thrombocythemia. Higher age
      showed significant associations with the BFI (Brief Fatigue Inventory) score,
      early satiety, concentration problems, dizziness, insomnia, cough and weight
      loss. Blood values, disease duration and myelosuppressive treatment did not
      significantly associate with any of the MPN-SAF items, with the exception of
      higher hemoglobin, which correlated with sad mood. Male patients with MPN scored
      significantly higher as regards sexual problems and weight loss compared to
      female patients. Overall, the MPN-SAF was found to be a valid instrument for
      assessing symptomatic burden among this population.

PMID- 21883030
TI  - Induction treatment of light chain deposition disease with bortezomib: rapid
      hematological response with persistence of renal involvement.

PMID- 21883031
TI  - Trafermin for stroke recovery: is it time for another randomized clinical trial?
AB  - INTRODUCTION: Basic fibroblast growth factor (bFGF) has been shown to reduce
      volume in acute ischemic stroke models, and to promote functional recovery as
      well as new synapse formation when given to animals with completed cerebral
      infarction. A recombinant native form of human bFGF, trafermin, has been tested
      in Phase III clinical trials in patients with stroke. AREAS COVERED: The role of
      trafermin in stroke. Data were identified by searching PubMed for single or
      combined terms including: trafermin, basic fibroblast growth factors,
      neuroprotection, neuroprotective drugs, stroke therapy, stroke rehabilitation and
      acute stroke. Original research papers, clinical series and reviews are included.
      Our research covered all relevant data up until 1 April 2011. EXPERT OPINION: To
      date, all Phase III trials have failed to demonstrate the superiority of
      trafermin over placebo when given within 6 h from stroke onset because trafermin
      causes a dose-dependent hypotension and an increased mortality rate in treated
      patients. However, a 24-h intravenous infusion seems to be safe for stroke
      patients and may result in an improved outcome when given 5 - 6 h after infarct.
      This finding may open renewed interest in restorative treatment for stroke, which
      could enhance recovery mechanisms rather than immediate neuroprotection. Studies
      suggest that growth factors can produce improvement in animal models of stroke,
      even when administered at postischemic intervals from many hours to days, when
      conventional neuroprotective approaches are typically ineffective. Because of the
      number of side effects and increased mortality reported in the first clinical
      studies with high dose of FGF, further experimental studies are necessary to
      asses whether it is possible to achieve a pharmacologically significant
      therapeutic level in the brain, by minimizing peripheral side effects. Another
      randomized clinical trial is needed to test trafermin in stroke patients but to
      enhance functional recovery.

PMID- 21883032
TI  - Safety of hymenoptera venom immunotherapy: a systematic review.
AB  - INTRODUCTION: The efficacy of venom immunotherapy (VIT) in patients with insect
      sting allergy is not questioned. However, its safety, especially when honeybee is
      used, is a matter of concern. AREAS COVERED: A systematic review of the
      literature on VIT was done, with both aqueous and depot extracts, to compare the
      frequency of systemic reactions to honeybee and vespid venoms. A Medline search
      was performed using the keywords 'venom immunotherapy', 'safety' and
      'tolerability'. The articles obtained were analyzed regarding the total number of
      patients treated with either honeybee or vespid VIT, the number and severity of
      systemic reactions during therapy, the type of extract used (aqueous or depot)
      and the administration regimen. EXPERT OPINION: The incidence of systemic
      reactions to VIT was 25.1% for honeybee venom and 5.8% for vespid venom (p <
      0.0001), while it was similar with aqueous and depot extracts in the whole
      population of patients. This confirms that during VIT systemic reactions are
      significantly more frequent with honeybee venom compared with vespid venom, while
      there are no significant overall differences in systemic reactions between
      aqueous and depot extracts.

PMID- 21883033
TI  - Pharmacokinetic evaluation of fluconazole in critically ill patients.
AB  - INTRODUCTION: Invasive candidiasis has emerged over the last few decades as an
      increasingly important nosocomial problem for the critically ill, affecting
      around 2% of intensive care unit patients. Although poor outcomes associated with
      invasive candidiasis among critically ill patients may relate to severe
      underlying disease processes and delayed institution of antifungal therapy,
      inadequate dosing of antifungal agents may also contribute. AREAS COVERED: This
      drug evaluation provides a critical appraisal of the published literature
      pertaining to the pharmacokinetics of fluconazole in critically ill, obese or
      severely burned patients, including those receiving acute renal replacement
      therapy. The pharmacodynamics of fluconazole is also covered, as well as the
      likely clinical implications for optimal dosing and the toxicity of fluconazole.
      Last, variations in fluconazole susceptibility patterns of Candida spp. are also
      discussed. EXPERT OPINION: Recently, there has been an increased but
      geographically variable prevalence of non-albicans Candida spp., causing invasive
      candidiasis and an overall trend towards reduced fluconazole susceptibility. The
      pathophysiological changes of critical illness, coupled with a lack of dose
      finding studies, support the use of local susceptibility patterns to guide
      fluconazole dosing until such time as pharmacokinetic-pharmacodynamic information
      to guide optimal fluconazole dosing strategies and pharmacodynamic targets
      becomes available.

PMID- 21883034
TI  - Linagliptin for the treatment of type 2 diabetes.
AB  - Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of antidiabetic agents
      that have been rapidly adopted since their introduction in 2006. There are now
      five agents in global use, with three approved for treatment of patients with
      type 2 diabetes (T2D) in the USA. The results of Phase III clinical trials for
      linagliptin, a new addition to this class of inhibitors (approved by the FDA on 2
      May 2011), have now been published. We reported on a 24-week Phase III trial of
      linagliptin administered as monotherapy in patients with T2D. This agent is
      characterized by a pharmacokinetic and metabolic profile that may have important
      implications for the choice of treatment in certain patient populations.

PMID- 21883035
TI  - Evaluation of respiratory viral pathogens in acute asthma exacerbations during
      childhood.
AB  - OBJECTIVE: Common upper respiratory tract viruses are the most frequent and
      important causes of asthma exacerbations in both children and adults. Prospective
      epidemiologic studies report that up to 80% of childhood exacerbations are
      associated with viral upper respiratory tract infections. MATERIALS AND METHODS:
      The study group consisted of 104 children with asthma aged 3-17 years who
      received treatment for asthma exacerbations in our clinic between September 2009
      and 2010. Nasopharyngeal and nasal swabs were obtained from all patients during
      an acute attack, and from the control group (31 subjects). These specimens were
      investigated for the presence of viral respiratory pathogens using a real-time
      multiplex PCR method. The patients were compared for the presence of respiratory
      pathogens and factors related to the severity of the asthma exacerbation.
      RESULTS: A pathogenic respiratory virus was detected in 53.8% of patients in the
      acute exacerbation group. The most commonly encountered viral agent was
      Rhinovirus (35.6%). Patients who had an acute exacerbation with or without a
      detectable viral pathogen were compared according to the severity of the
      exacerbation, the need for systemic steroids, and hospitalization rates. No
      statistically significant difference was found. CONCLUSION: Although viral upper
      respiratory tract infections are the most common cause of asthma exacerbations,
      the severity level of the exacerbation seems to be independent of whether a
      respiratory virus has been detected.

PMID- 21883036
TI  - An assessment of dose accuracy and injection force of a novel prefilled insulin
      pen: comparison with a widely used prefilled insulin pen.
AB  - OBJECTIVE: FlexTouch(r) (FT) (Novo Nordisk A/S, Bagsvaerd, Denmark) is a new
      prefilled insulin pen with a novel injection mechanism encompassing no push
      button extension at any dose-setting. This study assessed the dose accuracy and
      injection force of FT compared with the established Next Generation FlexPen(r)
      (NGFP) (Novo Nordisk A/S Bagsvaerd, Denmark). RESEARCH DESIGN AND METHODS: Dose
      accuracy was measured at the minimum, medium and maximum doses (FT, 1, 40 and 80
      international units (IU) and NGFP, 1, 30 and 60 IU). Injection force was measured
      during the injection of the maximum dose (FT, 80 IU; NGFP, 60 IU). MAIN OUTCOMES:
      FT and NGFP delivered insulin accurately and consistently at all doses (mean +/-
      s.d., FT at 1 IU, 0.98 +/- 0.07; 40 IU, 39.86 +/- 0.33; 80 IU, 79.76 +/- 0.64;
      NGFP at 1 IU, 1.02 +/- 0.08; 30 IU, 29.69 +/- 0.30; 60 IU, 59.50 +/- 0.51). FT
      had a significantly (p < 0.0001) lower injection force than NGFP. CONCLUSIONS:
      The study demonstrated that FT and NGFP deliver insulin accurately and
      consistently at low, medium and high doses. The novel torque spring injection
      mechanism of FT results in a significantly lower injection force than NGFP and a
      pen requiring less thumb-pressure to inject insulin may be welcomed by many
      people with diabetes.

PMID- 21883037
TI  - Apoptotic, antioxidant and antiradical effects of majdine and isomajdine from
      Vinca herbacea Waldst. and kit.
AB  - In the present study, apoptotic, antioxidant and antiradical effects of majdine
      and isomajdine from Vinca herbacea Waldst. and Kit were studied. For testing the
      possible apoptotic effects of majdine and isomajdine from V. herbacea, DNA
      fragmentation assay was conducted on the rat brain cortical tissue homogenates,
      in vitro. Also their possible effects on mitochondrial activity were tested by
      using the same tissue samples of rats. In addition, the antioxidant activity of
      isomajdine and majdine was determined using various in vitro antioxidant assays,
      including 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS(*+))
      radical scavenging and N,N-dimethyl-p-phenylenediamine (DMPD(*+)) radical
      scavenging, ferric ions (Fe(3+)) and cupric ions (Cu(2+)) reducing abilities and
      ferrous ions (Fe(2+)) chelating activity. On the other hand, butylated
      hydroxyanisole (BHA), butylated hydroxytoluene (BHT), alpha-tocopherol and trolox
      (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) were used as reference
      antioxidants.

PMID- 21883038
TI  - Anti-cancer characteristics of mevinolin against three different solid tumor cell
      lines was not solely p53-dependent.
AB  - Mevinolin (MVN) has been used clinically for the treatment of
      hypercholesterolemia with very good tolerance by patients. Based on
      epidemiological evidences, MVN was suggested strongly for the treatment of
      neoplasia. Early experimental trials suggested the mixed apoptotic/necrotic cell
      death pathway was activated in response to MVN exposure. Herein, the cytotoxic
      profile of MVN was evaluated, compared to the robust and frequently used anti
      cancer drug doxorubicin (DOX), against breast (MCF-7), cervical (HeLa) and liver
      (HepG(2)) transformed cell lines. MVN was showed comparable results in cytotoxic
      profile with DOX in all tested solid tumor cell lines. In addition, the MVN
      induced cytotoxicity was inferred to be multi-factorial and not solely dependent
      on p53 expression. It was concluded that molecular and genetic assessment of MVN
      induced cell death would be useful for developing cancer therapeutic treatments.

PMID- 21883039
TI  - Antiproliferative activity of some 1,4-dimethylcarbazoles on cells that express
      estrogen receptors: part I.
AB  - Several 9H-carbazole derivatives are used for various pharmacological
      applications. Many of these compounds demonstrated cytotoxic and anticancer
      activities. In this work, we have investigated the cytotoxic activity of some
      substituted carbazoles against cancer cell lines (MCF-7, and ISK). The derivative
      2a showed the highest inhibitory activity against both cell lines.

PMID- 21883040
TI  - Using C60 fullerenes for photodynamic inactivation of mosquito iridescent
      viruses.
AB  - This article describes the photodynamic inactivation of mosquito iridescent virus
      (MIV) Aedes flavescens in the presence of water-soluble C(60) fullerenes. It has
      been observed that the photodynamic inactivation of MIV for about 1 h reduces the
      infectious titre of the virus in large wax-moth larvae Galleria mellonella to 4.5
      lg ID(50)/mL. The influence of the C(60) concentration on its anti-viral activity
      was tested in the concentration range from 1 to 0.001 mg/mL. It has been found
      that C(60) is able to inactivate the iridovirus even in low concentrations.
      Consequently, the findings of this work suggest that photoexcited C(60)
      fullerenes can be successfully used for the inactivation of iridoviruses in
      biological systems.

PMID- 21883041
TI  - Effects of some metals on paraoxonase activity from shark Scyliorhinus canicula.
AB  - Paraoxonase (PON) is an organophosphate hydrolyser enzyme which also has
      antioxidant properties in metabolism. Due to its crucial functions, the
      inhibition of the enzyme is undesirable and very dangerous. PON enzyme activity
      should not be altered in any case. Inhibitory investigations of this enzyme are
      therefore important and useful. Metal toxicology of enzymes has become popular in
      the recent years. Here, we report the in vitro inhibitory effects of some metal
      ions, including Ni(2+), Cd(2+), Cu(2+) and Hg(2+), on the activity of shark serum
      PON (SPON). For this purpose, we first purified the enzyme from shark
      Scyliorhinus canicula (LINNAEUS, 1758) serum and analysed the alterations in the
      enzyme activity in the presence of metal ions. The K(M) and V(max) is 0.227 mM
      and 454.545 U/mL, respectively. The results show that metal ions exhibit
      inhibitory effects on SPON1 at low concentrations with IC(50) values ranging from
      0.29 to 2.00 mM. Copper was determined to be the most effective inhibitor with
      IC(50) of 0.29 mM.

PMID- 21883044
TI  - Redox eustress: roles for redox-active metabolites in bacterial signaling and
      behavior.
AB  - SIGNIFICANCE: Plant biologists and microbiologists have long discussed and
      debated the physiological roles of so-called "redox-active metabolites." These
      are natural products with unusually high redox activity that are not directly
      required for active growth. Generally, the biological roles of these compounds
      have been ascribed to interspecies competition and virulence, and they have been
      considered important sources of distress. RECENT ADVANCES: In this review, we
      discuss two examples of redox-active metabolites: nitric oxide and phenazines.
      Both are known for their toxic effects in some organisms and conditions but have
      recently been shown to provide benefits for some organisms under other
      conditions. CRITICAL ISSUES: Biologists are identifying new roles for redox
      active metabolites that are not directly related to their toxicity. These roles
      prompt us to suggest a dismissal of the paradigm that all biological stress is
      negative (i.e., distress). FUTURE DIRECTIONS: A more accurate view of redox
      couples requires characterization of their specific biological effects in a
      condition-dependent manner. The responses to these compounds can be termed
      "distress" or "eustress," depending on whether they inhibit survival, provide
      protection from a compound that would otherwise inhibit survival, or promote
      survival.

PMID- 21883045
TI  - Fortification of maternal milk for preterm infants.
AB  - During the last few decades, neonatal survival rates for preterm infants have
      markedly been improved. The American Academy of Pediatrics recommended that
      preterm neonates should receive sufficient nutrients to enable them to grow at a
      rate similar to that of fetuses of the same gestational age. Although human milk
      is the recommended nutritional source for newborn infants for at least the first
      six months of postnatal life, unfortified human breast milk may not meet the
      recommended nutritional needs of growing preterm infants. Human milk must
      therefore be supplemented (fortified) with the nutrients in short supply. The
      fortification of human milk can be implemented in two different forms: standard
      and individualized. The new concepts and recommendations for optimization of
      human milk fortification is the "individualized fortification". Actually, two
      methods have been proposed for individualization: the "targeted/tailored
      fortification" and the "adjustable fortification". In summary, the use of
      fortified human milk produces adequate growth in premature infants and satisfies
      the specific nutritional requirements of these infants. The use of individualized
      fortification is recommended.

PMID- 21883043
TI  - Warburg meets autophagy: cancer-associated fibroblasts accelerate tumor growth
      and metastasis via oxidative stress, mitophagy, and aerobic glycolysis.
AB  - SIGNIFICANCE: Here, we review certain recent advances in oxidative stress and
      tumor metabolism, which are related to understanding the contributions of the
      microenvironment in promoting tumor growth and metastasis. In the early 1920s,
      Otto Warburg, a Nobel Laureate, formulated a hypothesis to explain the
      "fundamental basis" of cancer, based on his observations that tumors displayed a
      metabolic shift toward glycolysis. In 1963, Christian de Duve, another Nobel
      Laureate, first coined the phrase auto-phagy, derived from the Greek words "auto"
      and "phagy," meaning "self" and "eating." RECENT ADVANCES: Now, we see that these
      two ideas (autophagy and aerobic glycolysis) physically converge in the tumor
      stroma. First, cancer cells secrete hydrogen peroxide. Then, as a consequence,
      oxidative stress in cancer-associated fibroblasts drives autophagy, mitophagy,
      and aerobic glycolysis. CRITICAL ISSUES: This "parasitic" metabolic coupling
      converts the stroma into a "factory" for the local production of recycled and
      high-energy nutrients (such as L-lactate)-to fuel oxidative mitochondrial
      metabolism in cancer cells. We believe that Warburg and de Duve would be pleased
      with this new two-compartment model for understanding tumor metabolism. It adds a
      novel stromal twist to two very well-established cancer paradigms: aerobic
      glycolysis and autophagy. FUTURE DIRECTIONS: Undoubtedly, these new metabolic
      models will foster the development of novel biomarkers, and corresponding
      therapies, to achieve the goal of personalized cancer medicine. Given the central
      role that oxidative stress plays in this process, new powerful antioxidants
      should be developed in the fight against cancer.

PMID- 21883046
TI  - Assessment of physiological redox state with novel FRET protein probes.
AB  - SIGNIFICANCE: Development of redox-sensing fluorescent proteins (redox probe
      proteins) have enabled live imaging of the physiological redox state within a
      cell, generating new strategies for detecting changes in the redox state during
      developmental, pathogenic, and aging processes. Several of the probe proteins
      utilize their characteristic redox-sensing segments as linkers in between two
      fluorophores, where structural alternations of the segments lead to changes in
      FRET efficiencies across the fluorophores. In this review we summarize two types
      of novel FRET-based redox probe proteins, namely redox linker (RL)-derived probes
      and Redoxfluor. RECENT ADVANCES: After these FRET-based redox probe proteins were
      generated, their responsiveness toward redox-related compounds as well as toward
      reactive oxygen species or reducing stimuli was investigated in vitro. Notably,
      both the RL-derived probe and Redoxfluor were found to directly respond to the
      redox state of glutathione, a main redox-formulating compound, showing a
      promising property for their use in subsequent in vivo analyses. Redoxfluor was
      not only used for redox sensing in the cytoplasm, but also utilized for assessing
      the redox state within peroxisomes. CRITICAL ISSUES: In contrast to "one
      fluorophore" redox probes such as roGFP and rxYFP proteins, whose usage has been
      established and widely expanded to various experimental systems, FRET-based redox
      probes were invented very recently and their applications to in vivo studies are
      still in their infancy. FUTURE DIRECTIONS: FRET-based redox probes provide novel
      approaches for redox sensing that are complementary to other methodologies.

PMID- 21883047
TI  - Decellularized porcine brain matrix for cell culture and tissue engineering
      scaffolds.
AB  - The extracellular matrix (ECM) plays important roles in influencing cellular
      behavior such as attachment, differentiation, and proliferation. However, in
      conventional culture and tissue engineering strategies, single proteins are
      frequently utilized, which do not mimic the complex extracellular
      microenvironment seen in vivo. In this study we report a method to decellularize
      brain tissue using detergents. This decellularized brain matrix is rich in
      glycosaminoglycans and contains collagen I, collagen III, collagen IV, collagen
      V, collagen VI, perlecan, and laminin. By further processing the material into a
      liquid form, the brain matrix can be used as a cell culture coating. Neurons
      derived from human induced pluripotent stem cells plated on the brain matrix
      express neuronal markers and assume neuronal morphology. Additionally, the same
      material can potentially be used as a scaffold for tissue engineering as it
      reassembles upon injection in vivo to form a gel. Thus, our work demonstrates the
      ability to use decellularized brain ECM for cell culture and tissue engineering
      applications.

PMID- 21883049
TI  - Comparison of articulating and static spacers regarding infection with resistant
      organisms in total knee arthroplasty.
AB  - INTRODUCTION: The result of treatment of infections involving antibiotic
      resistant organisms in total knee arthroplasty (TKA) is often poor. We evaluated
      the efficacy of 2-stage revision in TKAs infected with resistant organisms and
      compared the clinical outcomes with articulating and conventional static spacers,
      in terms of both infection control and function. METHODS: In a prospective
      manner, from June 2003 to January 2007 selected patients with a TKA infected with
      resistant organisms were enrolled and treated with 2-stage re-implantation. The
      45 patients were divided into 2 groups: group A (23 patients) implanted with the
      articulating spacers and group S (22 patients) implanted with static spacers. All
      patients followed the same antibiotic protocols and had the same re-implantation
      criteria. The efficacy of infection control was evaluated using re-implantation
      rate, recurrence rate, and overall success rate. The functional and radiographic
      results were interpreted with the Hospital of Special Surgery (HSS) knee score
      and the Insall-Salvati ratio. RESULTS: With mean 40 (24-61) months of follow-up,
      22 of 23 knees were re-implanted in group A and 21 of 22 were re-implanted in
      group S. Of these re-implanted prostheses, 1 re-infection occurred in group A and
      2 occurred in group S. Range of motion after re-implantation, the final
      functional scores, and the satisfaction rate were better in group A. One third of
      the patients in group S, and none in group A, had a patella baja. INTERPRETATION:
      After 2-stage re-implantation of TKAs originally infected with resistant
      organisms, the clinical outcome was satisfactory-and similar to that reported
      after treatment of TKAs infected with low-virulence strains. Treatment with an
      articulating spacer resulted in better functional outcome and lower incidence of
      patella baja.

PMID- 21883050
TI  - Epidemiology and treatment of distal radius fractures in Reykjavik, Iceland, in
      2004. Comparison with an Icelandic study from 1985.
AB  - BACKGROUND AND PURPOSE: Recent literature suggests that the incidence and
      treatment modalities of distal radius fractures have been changing over the past
      2 decades in the developed world. We examined the epidemiology of adult distal
      radius fractures in Iceland in 2004 and compared it with an Icelandic study from
      1985 and other studies. METHODS: A retrospective study of the epidemiology,
      classification, and treatment of distal radius fractures in Reykjavik residents
      aged 16 and older in 2004 was conducted by analysis of medical records and re
      evaluation of all radiographic examinations. RESULTS: The 228 fractures included
      in our material yielded an overall annual incidence of 17/10(4) in men and
      37/10(4) in women. Age-specific incidence rose steadily with age in both sexes.
      One third of the fractures were intraarticular, and working-age men accounted for
      a large proportion of them. 95% of fractures were treated nonoperatively.
      INTERPRETATION: The annual incidence of distal radius fractures was similar in
      1985 and 2004. However, age-specific incidence in younger postmenopausal women
      decreased sharply. This trend has also been observed in recent Scandinavian
      studies. Most fractures were treated nonoperatively in Iceland in 2004.

PMID- 21883051
TI  - Sequence context for transcription and translation of the Arabidopsis RPL23aA and
      RPL23aB paralogs.
AB  - The 80S cytoplasmic ribosome is responsible for translating the transcriptome
      into the proteome. Demand for ribosome production depends on growth rate, and
      both the ribosomal RNA (rRNA) and ribosomal protein (RP) components must respond
      coordinately and rapidly to positive and negative growth stimuli to prevent
      deleterious effects of excess or insufficient subunits. The 81 RPs of the
      Arabidopsis 80S ribosome are encoded by multigene families that often exhibit
      overlapping patterns of transcript accumulation; however, only one isoform of
      each RP family (with the exception of a small number of acidic RPs) assembles
      into a single ribosome. Here we dissected the regulatory regions (RRs) of both
      members of the RPL23a family (RPL23aA and RPL23aB) to identify salient cis-acting
      elements involved in transcriptional, posttranscriptional, and translational
      regulation of expression. Full length and truncated RRs of RPL23a paralogs were
      cloned upstream of a GUS reporter gene and expressed in Arabidopsis transgenic
      plants. High level expression in mitotically active tissues, driven by RPL23aA
      and RPL23aB RRs, required TATA-box, telo-box, and site II motif elements. First
      and second introns were found to play a minor role in posttranscriptional
      regulation of paralogs, and conserved transcript features (e.g., UTR base
      composition) may be involved in enhancing translational efficiency. Overall, our
      results indicate that RPL23a expression is governed by a complex network of
      multiple regulatory layers.

PMID- 21883053
TI  - Connected Community and Household Food-Based Strategy (CCH-FBS): its importance
      for health, food safety, sustainability and security in diverse localities.
AB  - In this article, I argue that Connected Community and Household Food-Based
      Strategy (CCH-FBS) could contribute to the resolution of outstanding
      nutritionally-related health problems. The 1995 Food-Based Dietary Guidelines
      (FBDGs) have been customized in regions and nations, encouraging integrated food
      systems and culturally-sensitive food-health relationships with economic
      development. Climate change and diminishing fuel and food affordability have made
      their role in promoting food security critical. Localities with their eco
      systems, communities and households, could apply FBDGs to correct mismatches
      between food systems, individual health needs, and environmental integrity.
      Improved infrastructure should allow communities and households to be usefully
      connected and operate with CCH-FBSs.

PMID- 21883052
TI  - Children's autonomous food acquisition in Mexican shantytowns.
AB  - Children's independent food-acquisition behaviors have been rarely studied
      outside of hunter-gatherer contexts, yet millions of children worldwide search,
      work, trade, or beg for food. This study uses observational, anthropometric,
      dietary, and ethnographic data to understand preliminarily the nutritive and
      possible social contexts of autonomous middle childhood food-gaining behaviors in
      Mexican shantytowns. While we find children forage, work for, and share
      considerable amounts of food outside the household, this is not associated with
      significant variation in their anthropometric status or dietary quality; some
      possible social benefits of food-getting are, however, evident.

PMID- 21883054
TI  - Potential contribution of mangoes to reduction of vitamin A deficiency in Kenya.
AB  - The beta-carotene content of fresh and dried mangoes commonly consumed in Kenya
      was evaluated and converted to retinol equivalent (RE). Mango fruits of varieties
      Ngowe, Apple, and Tommy Atkins were harvested at mature green, partially ripe,
      and ripe stages and their beta-carotene content analyzed. The stability of beta
      carotene in sun dried mangoes was also studied over 6 months under usual
      marketing conditions used in Kenya. The effect of using simple pretreatment
      methods prior to drying of mango slices on retention of beta-carotene was as well
      evaluated. In amounts acceptable to children and women, fresh and dried mangoes
      can supply 50% or more of the daily required retinol equivalent for children and
      women. Stage of ripeness, variety, postharvest holding temperature, method of
      drying, and storage time of dried mango slices affected beta-carotene content and
      consequently vitamin A value of the fruits. Apple variety grown in Machakos had
      the highest beta-carotene. It exceeded the daily RE requirements by 11.8% and
      21.5% for women and children respectively. Fresh or dried mangoes are a
      significant provitamin A source and should be included in food-based approaches
      aiming to reduce vitamin A deficiency.

PMID- 21883055
TI  - Wild edible plants used by the people of Manang district, Central Nepal.
AB  - Plant diversity plays an important role in maintaining the world's foods demands.
      Even today in Manang, a remote, mountainous district within the Annapurna
      Conservation Area, Nepal, local people gather substantial amounts of wild plants
      to meet their daily nutritional needs, with several species also used for trade.
      There has been little documented regarding the use of these wild foods, which
      play a part in both daily nutrition, and survival during times of famine.
      Moreover, planning for development, land use, economic growth and biodiversity
      conservation has not taken them into account. Information about edible wild plant
      use was gathered by interviewing knowledgeable villagers over a period of five
      years (2002-2006). In total, 41 plant species were used as sources of fruits,
      juice, vegetables, and achar (local relish or pickle). Several wild food plants
      that need intensive processing before consumption were documented, including the
      calcium oxalate containing Arisaema species. The traditional knowledge of use of
      wild food plants is decreasing in many parts of the world with the introduction
      of modern packed food items and Manang is not the exception. The results of this
      research will help to play a catalytic role to encourage dialogue among the
      people of Manang, and national and international scientific communities regarding
      long term bioprospecting research, and shape the creation of a rural livelihood
      strategy. Analysis of the nutritive and health values of some of these edible
      plant species may encourage the scientific community to build partnerships with
      local community to work towards long term sustainable utilization and
      conservation.

PMID- 21883056
TI  - Effect of a nutrition education program and diet modification in Beninese
      adolescent girls suffering from mild iron deficiency anemia.
AB  - A 26-week nutrition intervention, including 4 weeks of nutrition education,
      combined with an increase in the content and bioavailability of dietary iron for
      22 weeks was carried out in 34 intervention and 34 control adolescent girls
      suffering from mild iron deficiency anemia (IDA). In post-intervention,
      hemoglobin and serum ferritin were significantly higher in the intervention
      group, whereas the incidence of IDA was significantly lower in the intervention
      group compared to the control group. Nutrition knowledge scores were
      significantly higher in intervention girls compared to control girls. Dietary
      changes to improve available dietary iron can reduce iron deficiency anemia.

PMID- 21883057
TI  - Formative research for a healthy diet intervention among inner-city adolescents:
      the importance of family, school and neighborhood environment.
AB  - OBJECTIVES: To understand influences on diet among low-income African-American
      adolescents in East Baltimore. METHODS: Formative research was conducted for a
      food store-centered healthy diet intervention targeted to inner-city youth.
      Family, school and neighborhood influences on eating habits and health concepts
      were explored. RESULTS: Family structure, economic resources and past experiences
      influence what food means to adolescents. Healthy food in school and local stores
      is limited. Terminology to categorize foods was identified, including the term
      "home foods". CONCLUSIONS: Suggested adolescent nutritional interventions include
      promotion of home-based eating, improving availability of healthy foods in school
      and neighborhood stores, and targeted educational materials.

PMID- 21883058
TI  - Arsenic in Mexican children exposed to contaminated well water.
AB  - This cross-sectional study measures the arsenic level in school children exposed
      to contaminated well water in a rural area in Mexico. Arsenic was measured in
      hair by hydride generation atomic absorption spectrophotometry. Overall, 110
      children were included (average 10 years-old). Among 55 exposed children, mean
      arsenic level on hair was 1.3 mg/kg (range <0.006-5.9). All unexposed children
      had undetectable arsenic levels. The high level of arsenic in water was
      associated to the level in hair. However, exposed children drank less well water
      at school or at home than unexposed children, suggesting that the use of
      contaminated water to cook beans, broths or soups may be the source of arsenic
      exposure.

PMID- 21883059
TI  - Level of adherence to the Mediterranean diet among elderly individuals living in
      Mediterranean islands: nutritional report from the Medis Study.
AB  - The aim of this work was to evaluate the level of adherence to the traditional
      Mediterranean diet among 1190 elderly adults living in the Greek islands and
      Cyprus. METHODOLOGY: The retrieved information included demographic, bio-clinical
      and dietary characteristics. RESULTS: The level of adherence to this dietary
      pattern was 61% in both men and women. People in rural areas had slightly higher
      level of adherence compared to those living in urban areas (62% vs. 60%).
      CONCLUSION: The level of adherence to the traditional Mediterranean diet was
      moderate. People living in rural areas seem to better hold these traditional
      dietary habits.

PMID- 21883060
TI  - Dietary adequacy of Indian children residing in an urban slum--analysis of
      proximal and distal determinants.
AB  - The influences of proximal and distal determinants of dietary adequacy of
      children from an urban slum in India were analyzed. Children numbering 271 (5-14
      years) and their mothers were enrolled for the study. Intake of all nutrients
      except protein was inadequate in the dietaries of children. Among distal
      determinants, associations were found between (i) calorie intake and maternal
      nutritional status; (ii) protein, iron and B-complex intakes and economic status,
      and (iii) retinol, calcium and fat intakes and family size. Literacy status was
      not associated with dietary adequacy. Age of children and economic status of
      family were important determinants of dietary adequacy of children from slum
      area.

PMID- 21883061
TI  - Cultivar effect on Moringa oleifera glucosinolate content and taste: a pilot
      study.
AB  - Leaves of the tropical tree Moringa oleifera are widely promoted in areas of
      chronic malnutrition as nutritional supplements for weaning infants and nursing
      mothers. Adoption, in these circumstances may hinge upon taste, which can vary
      greatly amongst cultivars. It is widely assumed that this taste variation is
      primarily germplasm-dependent, and results from the breakdown of glucosinolates
      to isothiocyanates. Leaves of 30 accessions, grown at a single field plot, were
      sampled 3 times over the course of a year. Taste, assessed in a masked protocol,
      was not related to glucosinolate content of the leaves.

PMID- 21883063
TI  - Beliefs about infant feeding in China and the United States: implications for
      breastfeeding promotion.
AB  - This study investigates cultural differences in mothers' views regarding infant
      feeding and socialization. The majority of mothers reported breastfeeding as one
      of their methods of infant feeding, although more than half reported using both
      breast and bottle. Mothers in China expressed concerns that breastfeeding is not
      compatible with work outside of the home. American mothers were more likely to
      believe that breastfeeding is difficult to establish. "Happiness" was ranked the
      most important socialization goal by both groups. Public health initiatives must
      be culturally relevant and reflect an understanding of parenting values and
      beliefs.

PMID- 21883062
TI  - Trends of overweight and obesity among children in Tijuana, Mexico.
AB  - The objectives of this study were to compare the trends of obesity from 2001-02
      to 2006-07 in school children of Tijuana, Mexico and to investigate the
      relationship with the child's gender and type of school attended. Bietapic random
      sample was selected by cluster of schools and groups. Results of the 1684
      children from 6-14 years of age assessed showed an overall prevalence of obesity
      (> 95(th)) of 28%. An overall increase of overweight and obesity of 7-percentage
      points (p=0.0003), from 41 to 48%, being higher among boys and younger girls.
      Prevalence of obesity was higher among boys and children from private schools.

PMID- 21883064
TI  - Intergenerational participatory discussion groups foster knowledge exchange to
      improve child nutrition and food security in northern Malawi.
AB  - This article assesses the effectiveness of a participatory, intergenerational,
      dialogue approach in addressing gender and generational conflicts related to both
      child nutrition and agriculture. Analysis of 46 interviews and 3 focus groups
      with smallholder farmers in rural agrarian communities with high rates of child
      malnutrition in northern Malawi suggested that participatory discussion can lead
      to positive change, including increasing child feeding frequency and dietary
      diversity. An intergenerational, transformative, and holistic approach to
      nutrition education which integrates agricultural and gender issues can
      effectively address sensitive conflicts within households and communities that
      affect child nutrition, and come up with local solutions.

PMID- 21883065
TI  - Egg contribution towards the diet of pregnant Latinas.
AB  - Proper nutrition during gestation is important to prevent adverse pregnancy
      outcomes. Eggs contain many important nutrients necessary for fetal development
      and human survival. Three focus groups were conducted with Latina women living in
      Connecticut to identify cultural beliefs toward egg consumption during pregnancy,
      traditional egg dishes, and methods of preparation. A cross-sectional study was
      then carried out with a sample of predominately Puerto Rican pregnant Latinas (N
      = 241) to identify the frequency of consumption of eggs and egg-containing dishes
      as well as methods of preparation using a tailored food frequency questionnaire
      modified for this population. Paired sample t-tests were used to examine if there
      were differences in weekly mean egg intake patterns between the year prior to the
      pregnancy and during pregnancy based on a Food Frequency Questionnaire. Women
      were categorized into eggs consumers and non-consumers if they consumed or did
      not consume eggs during the previous day based on 24-hour recall data.
      Independent-sample t-test and chi-square cross-tabulation analyses were conducted
      to examine the association between egg consumption and nutrient intake
      categories. Results showed that eggs and egg-containing traditional dishes are
      consumed by Latinas before and during pregnancy. Egg consumers had higher intakes
      of protein, fat, vitamin K, vitamin E, selenium, beta carotene, lutein and
      zeaxanthin, cholesterol, total polyunsaturated fatty acids, and docosahexaenoic
      acid. Eggs contribute significantly to the diet of pregnant Latinas.

PMID- 21883066
TI  - Changes in food habits of south Indian Hindu Brahmin immigrants in State College,
      PA.
AB  - This study was conducted to understand the factors influencing changes in the
      food habits of south Indian Brahmin immigrants in State College, PA. Data was
      collected from participants (n = 28) using a semi-structured interview based on
      the PRECEDE framework, and participant observations. Analysis of the data used
      grounded theory generated themes highlighting their food acculturation
      experience. Adjusting in State College was described as a "delicate balance" that
      meant maintaining their south Indian traditions while at the same time adapting
      to the cultural milieu of a town that favored north Indian cuisine, and "blending
      in" with the larger American society.

PMID- 21883068
TI  - Global food terror in Japan: media shaping risk perception, the nation, and
      women.
AB  - This article traces the Japanese media's response to Chinese poison pot-stickers
      (gyoza) in Japan's food system as they debate and guide consumer-citizens'
      feelings of increasing vulnerability as individuals in the global market, the
      nation, and families. Global food becomes a key metaphor for threats to national
      borders and the need for national food, yet simultaneously for inevitable risk to
      globally attuned stomachs that can be controlled only by alert housewives and
      education of the young. Food terror effectively signals citizens' lack of
      protection in risk society, but leaves unsaid important differences among
      consumer-citizens to save themselves with scarce Japanese-made food.

PMID- 21883069
TI  - Moving beyond hunger and nutrition: a systematic review of the evidence linking
      food insecurity and mental health in developing countries.
AB  - Food insecurity is a significant problem in the developing world, and one that is
      likely to increase given the current global food crisis spurred by rising oil
      prices, conversion of food to biofuels, and reduced harvests in the wake of
      natural disasters. The impacts of food insecurity on nutrition status, growth,
      and development are well substantiated; less is known about the non-nutritional
      impacts of food insecurity, such as its effects on mental health. This systematic
      review assesses current findings regarding the impacts of food insecurity on
      mental health in developing countries. Both qualitative and quantitative studies
      are considered. The results of the search reveal that little work has examined
      these issues directly, and serious methodological flaws are present in many of
      the existing studies. Gaps in the literature, implications, and research
      priorities are discussed.

PMID- 21883070
TI  - Intracultural diversity in food knowledge in southern Brazil.
AB  - This research explores the social distribution of food knowledge in Ribeirao
      Preto, a city in the state of Sao Paulo, Brazil. Through an analysis of the
      distribution of individual expertise in regard to the cultural model of food
      along the dimensions of healthfulness, practicality, and prestige, this research
      demonstrates that knowledge of the cultural model of food is most strongly shared
      in the upper class of the city. Qualitative and quantitative ethnographic
      research suggests that the social patterning of health-related food knowledge in
      Ribeirao Preto may serve to maintain class distinction.

PMID- 21883071
TI  - Ethnobotany of food plants in the high river Ter valley (Pyrenees, Catalonia,
      Iberian Peninsula): non-crop food vascular plants and crop food plants with
      medicinal properties.
AB  - The present study reports a part of the findings of an ethnobotanical research
      project conducted in the Catalan region of the high river Ter valley (Iberian
      Peninsula), concerning the use of wild vascular plants as food and the medicinal
      uses of both wild and cultivated food plants. We have detected 100 species which
      are or have been consumed in this region, 83 of which are treated here (the
      remaining are the cultivated food plants without additional medicinal uses). Some
      of them, such as Achillea ptarmica subsp. pyrenaica, Convolvulus arvensis,
      Leontodon hispidus, Molopospermum peloponnesiacum and Taraxacum dissectum, have
      not been previously reported, or have only very rarely been cited or indicated as
      plant foods in very restricted geographical areas. Several of these edible wild
      plants have a therapeutic use attributed to them by local people, making them a
      kind of functional food. They are usually eaten raw, dressed in salads or cooked;
      the elaboration of products from these species such as liquors or marmalades is a
      common practice in the region. The consumption of these resources is still fairly
      alive in popular practice, as is the existence of homegardens, where many of
      these plants are cultivated for private consumption.

PMID- 21883072
TI  - What changes when we move? A transnational exploration of dietary acculturation.
AB  - This study aimed to explore Mexican dietary acculturation patterns among
      immigrants using a unique transnational photographic assessment. Participants (N
      = 10) were Latino mother and child pairs living in Mexico (1 pair) and in the
      United States (4 pairs). Data were collected in 2 phases: 1) participant
      observation and photography in Mexico, and 2) in-depth interviewing using
      photographic guides in North Carolina. Environment, daily activity patterns,
      shopping, and dietary patterns in Mexico were all documented. Acculturation
      resulted in poor dietary intake due to decreased availability, food displacement,
      and cost. Decreases in physical activity due to environmental and social barriers
      were also reported.

PMID- 21883073
TI  - Evaluation of self-care practices and emotional distress among people with Type 2
      diabetes mellitus in Dar es Salaam, Tanzania.
AB  - This study was conducted to determine self-care practices and diabetes related
      emotional distress among people with Type 2 diabetes mellitus in Dar es Salaam,
      Tanzania. A cross sectional survey-involving 121 Types 2 diabetics was conducted
      in 4 diabetic clinics located in Dar es Salaam. Anthropometric and biomedical
      measurements namely weight, height, waist, hip, mid-upper arm circumference,
      blood pressure and fasting blood glucose were measured. Self-care practices and
      diabetic related emotion distress were evaluated by using validated instruments.
      Results revealed that, the average fasting plasma glucose was 11.2 +/- 5.5
      mmol/l, blood pressure was 134.7/86.1 mm/Hg and the mean BMI for males and
      females were 25.0 +/- 4.3 and 27.0 +/- 5.1 kg/m(2), respectively. Subject's self
      care score for general diet, specific diet, physical exercise, foot-care and
      medication were 4.6 +/- 2.4, 3.7 +/- 1.5, 3.4 +/- 1.8, 3.6 +/- 2.8 and 5.5 +/-
      2.8 days per week, respectively. Self-monitoring of blood glucose was irregular
      and only 46.3% of the subjects tested their levels of blood glucose at least once
      in between the appointments (90 days). Low income was the major limitation for
      complying with the self-care practices related to diet, blood glucose testing and
      medication. It is recommended that, the Government of Tanzania should in the
      short run subsidize the prices of diabetes drugs, remove all taxes on the glucose
      test kits and establish a national diabetes program that would coordinate and
      oversee provision of the basic services such as screening, glucose testing,
      medication, counseling and management of the condition. In the long run, the
      government should establish a preventive public health program in order to
      curtail the escalation of diabetes. Further research should be conducted to
      determine how factors such as socio-cultural and demographic, self-care, and
      psychosocial distress interact to determine biomedical outcomes such as blood
      pressure, blood glucose and body mass index.

PMID- 21883074
TI  - Nutritive composition of Tarag, the traditional naturally-fermented goat milk in
      China.
AB  - Nutritive compositions were analyzed in 10 batches of samples of Tarag (the
      traditional naturally-fermented goat milk), which were collected in the Mongolian
      community in China. Results showed that Tarag had richer nutrients than yoghurt.
      Tarag-2 (from Zang goats) had better chemical nutrient density than Tarag-1 (from
      Chaidamu goats). Tarag was rich in casein, lactoferrin, serum albumin, beta
      lactoglobulin, alpha-lactalbumin, and 3 unknown fractions in certain samples.
      Microbiological enumeration revealed that Tarag contained large lactic acid
      bacteria and yeast. Tarag was judged nutritious and indicated the latent value
      for people's health.

PMID- 21883075
TI  - Is air temperature at birth associated with body mass index in 9-10 year-old
      children?
AB  - Several studies suggest that temperature (season) at birth affects body weight
      and obesity years later. This study related air temperature at birth to body mass
      index in Liverpool primary school children (n = 11,084). No association was found
      between body mass index categories and month or season of birth and only weak
      correlations with month of birth and air temperature at birth. These correlations
      disappeared when controlled for precise age and an index of deprivation but girls
      in the third quintile for deprivation had a higher body mass index if born in
      colder weather.

PMID- 21883076
TI  - National food control systems: lessons from Mauritius.
AB  - Food control systems are being established or revamped in many countries because
      of problems occurring along the food chain and the obligations of governments
      towards the World Trade Organization. The main components of an ideal food
      control system are food legislation, administration, enforcement and supporting
      bodies like analytical services and consumer organizations. Mauritius introduced
      modern legal instruments in 1998 in an attempt to reinvigorate food control. This
      article describes the components of the Mauritian Food Control System (MFCS). An
      appraisal of these components is then made. The methodology comprised a
      literature review and in-depth interviews with key informants and stakeholders of
      the local food control system. Although much progress was made with the
      introduction of new food legislation in 1998, other components of the local
      system like enforcement and various supporting bodies did not receive appropriate
      support. Other countries could use the lessons drawn from the Mauritian
      experience while setting up or upgrading their food control systems.

PMID- 21883078
TI  - The importance of baobab (Adansonia digitata L.) in rural West African
      subsistence--suggestion of a cautionary approach to international market export
      of baobab fruits.
AB  - The European Commission recently authorized the import of baobab (Adansonia
      digitata L.) fruit pulp as a novel food. In rural West Africa the multipurpose
      baobab is used extensively for subsistence. Three hundred traditional uses of the
      baobab were documented in Benin, Mali, and Senegal across 11 ethnic groups and 4
      agroecological zones. Baobab fruits and leaves are consumed throughout the year.
      The export of baobab fruits could negatively influence livelihoods, including
      reduced nutritional intake, change of power relations, and access rights.
      Capacity building and certification could encourage a sustainable and ethical
      trade of baobab fruits without neglecting baobab use in subsistence.

PMID- 21883079
TI  - Eating from the wild: Turumbu indigenous knowledge on noncultivated edible
      plants, Tshopo District, DRCongo.
AB  - Documenting and revalorizing the rapidly disappearing indigenous knowledge on
      wild edible plants is essential to promote health and preserve diversity. Focus
      group discussions were organized within three Turumbu villages to document wild
      foods known, availability, preparation methods, and uses. Preferences in taste
      and commercial, nutritional, and cultural value were discussed during
      participatory ranking exercises. Results show 85 species within 70 genera and 44
      families. Fruits of Anonidium manni and Landolphia owariensis, and (unfolded)
      leaves of Megaphrynium macrostachyum and Talinum triangulare are most
      appreciated. Inventories and preference rankings should be completed with
      nutritional analyses and market studies to set priorities for participatory
      domestication.

PMID- 21883080
TI  - Availability, preference, and consumption of indigenous forest foods in the
      Eastern Arc Mountains, Tanzania.
AB  - We investigated the availability, preference, and consumption of indigenous
      forest foods in Uluguru North (UNM) and West Usambara Mountains (WUM) of
      Tanzania. Data collection techniques involved focus group discussion, structured
      questionnaires, and botanical identification. Results revealed (1) there were 114
      indigenous forest food plant species representing 57 families used by communities
      living adjacent to the two mountains; (2) sixty-seven species supplied edible
      fruits, nuts and seeds: 24 and 14 species came from WUM and UNM, respectively,
      while 29 came from both study areas; (3) of the 57 identified vegetable species,
      22 were found in WUM only, 13 in UNM only, and 12 in both areas; (4) there were
      three species of edible mushrooms and five species of roots and tubers; (5)
      unlike the indigenous roots and tubers, the preference and consumption of
      indigenous vegetables, nuts, and seeds/oils was higher than exotic species in
      both study areas; and (6) UNM had more indigenous fruits compared to WUM,
      although preference and consumption was higher in WUM. We recommend increased
      research attention on forest foods to quantify their contribution to household
      food security and ensure their sustainability.

PMID- 21883081
TI  - Consumer attitudes towards vegetable attributes: potential buyers of pesticide
      free vegetables in Accra and Kumasi, Ghana.
AB  - Considering the inappropriate use of synthetic pesticides on vegetables in West
      Africa, the rationale behind this research was to assess the extent to which
      consumers can function as demanders of risk reduced vegetables and hence act as
      innovators towards vegetable safety. Using the cases of Kumasi and Accra in
      Ghana, the study examined possible consumer responses to product certification
      that communicates freedom from pesticides (e.g., organic certification).
      Generally, search attributes such as the fresh and healthy appearance of a
      vegetable were found to be central to consumer choice. While consumers stress the
      importance of health value, they are mostly unaware of agro-chemical risks
      related to vegetable consumption.

PMID- 21883082
TI  - Trying versus liking fruits and vegetables: correspondence between mothers and
      preschoolers.
AB  - Extensive research indicates that a diet rich in fruits and vegetables (F&V)
      protects against numerous illnesses in adulthood, but that most individuals,
      including children, consume far fewer F&V per day than is recommended. Since
      evidence suggests that eating habits in childhood track into adulthood, more
      research is necessary to learn about how parental F&V intake and opportunities
      influence child F&V consumption. The purpose of this study was to examine the
      relationship between mothers' F&V preferences and those of their preschool-age
      children to determine if greater maternal "liking" of fruits and vegetables was
      associated with their reports of their children's "trying" more fruits and
      vegetables. Eighty-three mothers completed a questionnaire that assessed whether
      they and their preschoolers had tried or liked a variety of F&V. Mothers liked
      86% of the fruits they tried, girls 76%, and boys 69%. Mothers liked 81% of the
      vegetables they tried; boys and girls liked 55%. Mothers' likes correlated with
      F&V that their children tried, but mothers' likes also limited the number of F&V
      that their children tried. Mothers reported preferences for F&V are associated
      with estimates of their preschoolers' preferences for F&V. Relative to girls,
      boys may need additional opportunities for F&V exposure.

PMID- 21883083
TI  - Evaluation of soy hulls as a potential ingredient of functional foods for the
      prevention of obesity.
AB  - The prevalence of obesity and its associated health problems is rising to
      epidemic proportions throughout the world. Soy hulls, an industrial waste from
      oil extraction, contain a high proportion of fiber--soluble and insoluble--and
      may be a potential ingredient of functional foods for the prevention of obesity.
      However, crude soybeans, as do all legumes, present challenges to their use
      because of intensive antitrypsin and antichimotrypsin activity that impairs
      normal growth in humans and other mammals, requiring inactivation. To evaluate
      possible antinutritional effects of soybean hulls, diets with 10 percent fiber
      from soybean hulls or cellulose were offered to weanling IIMb/Beta obese rats
      during their prepubertal timeframe. The fact that no significant differences were
      found in growth, blood parameters nor in fat depots' weight and lipid content
      plus the proven beneficial effects on obese adult rats suggest that soy hulls may
      be a useful ingredient of functional foods for the prevention and treatment of
      human obesity.

PMID- 21883084
TI  - Prevalence of sarcopenia among older community-dwelling people with normal health
      and nutritional state.
AB  - This study analyzed whether sarcopenia, a risk factor for disability in the aged,
      also occurs in healthy community-dwelling elders with normal nutritional state.
      As indicators, body cell mass (BCM) and lean body mass (LBM) were determined in
      110 Germans (ages 60-83) using bioimpedance analysis. Nutritional status, muscle
      function, anthropometry, and physical activity level were investigated.
      Sarcopenia was already present in well nourished healthy elders. Its prevalence
      depended on the measure of muscle mass used (BCM percent, 22 percent males, 20
      percent females; LBM percent, 4 percent males, 11 percent females). In
      conclusion, screening for presence of sarcopenia is needed in healthy, well
      nourished elderly populations requiring an international standardization.

PMID- 21883085
TI  - Sorghum malt and traditional beer (dolo) quality assessment in Burkina Faso.
AB  - Sorghum malt and dolo quality evaluation criteria and parameters affecting
      quality were surveyed in six cities in Burkina Faso through questionnaires
      addressed to malt processors, dolo processors, retailers, and consumers. The
      major quality criteria for malt quality assessment were perceived to be taste and
      presence/absence of roots in the malt. Taste, alcohol content, and wort
      sufficiently cooked were perceived as major criteria for the dolo quality
      assessment. The major parameters affecting malt quality were perceived to be malt
      production period, proportions of grain and the amount of water entering malting,
      presence of pesticide residues in the malting grains, and age of grain.
      Processing method, yeast source, proportions of the components (crushed grain,
      water, mucilage, yeast) entering dolo production, malt quality, wort temperature
      at time of inoculation, amount of energy available for cooking, wort and sediment
      boiling time, quality of mucilage, malt with non-sweet taste, presence/absence of
      roots in the malt, and ease of filtering crushed malt were perceived as major
      parameters affecting the dolo quality. These results will be used in the
      improvement of the dolo supply chain in Burkina Faso by providing more reliable
      information for training programs for efficient dolo brewing processes,
      development of best cropping practices to improve grain quality, and providing
      better selection criteria for sorghum breeding programs.

PMID- 21883087
TI  - Nutritional counseling in midwifery and obstetric practice.
AB  - It is generally acknowledged that pregnant women require healthy diets. However,
      the cultural idea of "eating for two" and what constitutes an "appropriate" diet
      during pregnancy have been contested grounds of research as guidelines have
      changed over the decades. Using a grounded theory approach, we examine how
      research on pregnancy nutrition is incorporated into practice and translated to
      patients by obstetricians and 2 categories of midwives--certified nurse midwives
      (CNMs) and direct-entry midwives (DEMs). Five themes emerged from interviews: (1)
      food and exercise as "two sides of the same coin"; (2) "good food" and "food that
      harms" dichotomies; (3) nutrition as holistic prevention; (4) institutionalized
      barriers to nutritional counseling; and (5) food and the obesity epidemic. An
      exploration of the conceptual connections between these themes by provider type
      suggests mechanisms that we argue may be functioning to produce, reproduce, and
      perpetuate midwifery and medical models of care and associated provider-effects
      on nutrition-related complications.

PMID- 21883088
TI  - Toward a sustainability label for food products: an analysis of experts' and
      consumers' acceptance.
AB  - The recent proliferation of standards and labels for organic, fair-trade, locally
      produced, and healthy food products risks creating confusion among consumers.
      This study presents a standardized approach to developing a comprehensive
      sustainability label that incorporates ecological, economic, and social values.
      The methodology is based on an extension of modular life-cycle assessment to non
      environmental sustainability criteria. Interviews with a wide range of experts
      (n=65) and a consumer survey (n=233) were conducted to analyze the feasibility
      and potential effectiveness of the approach. Responses indicated that a
      comprehensive sustainability label could considerably influence consumption
      patterns and facilitate cross-product comparisons.

PMID- 21883089
TI  - The modernization of cooking techniques in two rural Mayan communities of
      Yucatan: the case of lard frying.
AB  - The objective of this article is to provide information on cooking techniques
      used by two rural communities of Yucatan. We used a 24-hour recall method with
      275 participants consuming 763 dishes. Dishes were classified according to
      cooking technique: 205 were lard-fried (27%), 169 oil-fried (22%), and 389
      boiled/grilled (51%). The smaller more secluded community (San Rafael) consumed
      more fried dishes than the larger community (Uci) (54% versus 45%) and used more
      lard-frying than Uci (65% versus 46%). The more extensive use of lard in the
      smaller community appears to be due to fewer modernizing influences such as the
      availability and use of industrialized vegetable oils.

PMID- 21883090
TI  - An indigenous plant food used by lactating mothers in west Africa: the nutrient
      composition of the leaves of Kigelia africana in Ghana.
AB  - Although the leaves of Kigelia africana are used to make a palm-nut soup which is
      consumed mainly by lactating women in many parts of sub-Saharan Africa, little is
      known about the nutrient qualities of this underutilized and underappreciated
      plant food. Leaves of Kigelia africana, called "sausage tree" in English and
      "nufuten" in the Twi language of Ghana, were collected in Kumasi and analyzed for
      their content of nutritionally important fatty acids, amino acids, minerals, and
      trace elements. The dried leaves contained 1.62% fatty acids, of which alpha
      linolenic acid and linolenic acid accounted for 44% and 20%, respectively, of the
      total. Protein accounted for 12.6% of the dry weight and, except for lysine, its
      overall essential amino acid profile compared favorably to a World Health
      Organization protein standard for school children. Kigelia leaf contained
      considerable amounts of many essential elements, including calcium (7,620 MUg/g),
      iron (161 MUg/g), magnesium (2,310 MUg/g), manganese (14.6 MUg/g), zinc (39.9
      MUg/g), and chromium (0.83 MUg/g); selenium, however, was not detected. These
      data indicate that Kigelia africana leaf compares favorably with many other
      commonly-consumed green leafy vegetables such as spinach and provides a rational
      basis for promoting the conservation and propagation of the plant and encouraging
      its wider use in the diets of populations in sub-Saharan Africa.

PMID- 21883092
TI  - Effect of serum concentration on the cytotoxicity of clay particles.
AB  - Nanoparticle cytotoxicity testing based on in vitro methods frequently lack
      consistency. Even the inclusion of the commonly employed growth supplement, FCS
      (fetal calf serum), generates variable results. Thus, our object was to
      investigate the effect of FCS concentration on the cytotoxic behaviour of the
      unmodified nanoclay, Cloisite(r) Na(+). Human monocytic U937 cells in medium
      supplemented with 5% FCS, 2.5% FCS or serum-free medium were treated with 1 mg/ml
      Cloisite Na(+). Cell growth in 2.5% FCS was significantly inhibited by Cloisite
      Na(+) within 48 h, whereas little effect was seen with a supplement of 5% FCS.
      Without serum, cell growth was inhibited and Cloisite Na(+) had a detrimental
      effect on these cells. In media supplemented with FCS, the nanoclays agglomerated
      together to form large bundles, whereas they were evenly dispersed throughout the
      medium in the absence of serum. Clay particles, therefore, have cytotoxic
      properties that may be linked to their dispersion pattern. These adverse effects
      seem to be masked by 5% FCS. Serum supplementation is an important consideration
      in the toxicological assessments of nanomaterials on cells, which needs to be
      addressed in the standardization of in vitro testing methods.

PMID- 21883093
TI  - Critical roles of RNA helicase DDX3 and its interactions with eIF4E/PABP1 in
      stress granule assembly and stress response.
AB  - Upon environmental insults, SGs (stress granules) aid cell survival by serving as
      sites of translational silencing. RNA helicase DDX3 was reported to associate
      with SGs. However, its role in SG physiology remains undefined. We have
      demonstrated previously that DDX3 acts as an eIF4E (eukaryotic initiation factor
      4E)-inhibitory protein to suppress translation. In the present study, we
      indentified the SG marker PABP1 [poly(A)-binding protein 1] as another direct
      interaction partner of DDX3. We established various stimuli as novel stressors
      that direct DDX3 with eIF4E and PABP1 into SGs, but not to processing bodies.
      Interestingly, down-regulation of DDX3 interfered with SG assembly, led to
      nuclear accumulation of PABP1 and reduced cell viability following stress.
      Conversely, supplementation with a shRNA (short hairpin RNA)-resistant DDX3
      restored SG formation, the translocation of PABP1 into SGs and cell survival.
      Notably, the SG-inducing capacity of DDX3 is independent of its ATPase and
      helicase activities, but mapped to the eIF4E-binding region. Moreover, the eIF4E
      binding-defective mutant DDX3 was impaired in its SG-inducing ability and
      protective effect on cell survival under adverse conditions. All together, the
      present study has characterized DDX3 as a pivotal SG-nucleating factor and
      illustrates co-ordinative roles for DDX3, eIF4E and PABP1 in integrating
      environmental stress with translational regulation.

PMID- 21883094
TI  - PTEN interacts with metal-responsive transcription factor 1 and stimulates its
      transcriptional activity.
AB  - MTF-1 (metal-responsive transcription factor 1) is an essential mammalian protein
      for embryonic development and modulates the expression of genes involving in zinc
      homoeostasis and responding to oxidative stress. We report in the present paper
      that PTEN (phosphatase and tensin homologue deleted on chromosome 10) associates
      with MTF-1 in the cells. These two proteins interact via the acidic domain of MTF
      1 and the phosphatase/C2 domain of PTEN. Depletion of PTEN reduced MT
      (metallothionein) gene expression and increased cellular sensitivity to cadmium
      toxicity. PTEN did not alter the nuclear translocation, protein stability or DNA
      binding activity of MTF-1. Zinc increased MTF-1-PTEN interaction in a dose
      dependent manner. The interaction elevated within 2 h of zinc addition and
      declined afterwards in the cells. The enhanced binding activity occurred mainly
      in the cytoplasm and reduced after translocating the MTF-1 into the nucleus.
      Blocking signalling through the PI3K (phosphoinositide 3-kinase) pathway did not
      alter the zinc-induced MT expression. Analysis of enzymatically inactive PTEN
      mutants demonstrated that protein but not lipid phosphatase activity of PTEN was
      involved in the regulation of MTF-1 activity. The same regulatory role of PTEN
      was also noted in the regulation of ZnT1 (zinc transporter 1), another target
      gene of MTF-1.

PMID- 21883095
TI  - Reproducibility of cardiac power output and other cardiopulmonary exercise
      indices in patients with chronic heart failure.
AB  - Cardiac power output is a direct measure of overall cardiac function that
      integrates both flow- and pressure-generating capacities of the heart. The
      present study assessed the reproducibility of cardiac power output and other more
      commonly reported cardiopulmonary exercise variables in patients with chronic
      heart failure. Metabolic, ventilatory and non-invasive (inert gas re-breathing)
      central haemodynamic measurements were undertaken at rest and near-maximal
      exercise of the modified Bruce protocol in 19 patients with stable chronic heart
      failure. The same procedure was repeated 7 days later to assess reproducibility.
      Cardiac power output was calculated as the product of cardiac output and mean
      arterial pressure. Resting central haemodynamic variables demonstrate low CV
      (coefficient of variation) (ranging from 3.4% for cardiac output and 5.6% for
      heart rate). The CV for resting metabolic and ventilatory measurements ranged
      from 8.2% for respiratory exchange ratio and 14.2% for absolute values of oxygen
      consumption. The CV of anaerobic threshold, peak oxygen consumption, carbon
      dioxide production and respiratory exchange ratio ranged from 3.8% (for anaerobic
      threshold) to 6.4% (for relative peak oxygen consumption), with minute
      ventilation having a CV of 11.1%. Near-maximal exercise cardiac power output and
      cardiac output had CVs of 4.1 and 2.2%, respectively. Cardiac power output
      demonstrates good reproducibility suggesting that there is no need for performing
      more than one cardiopulmonary exercise test. As a direct measure of cardiac
      function (dysfunction) and an excellent prognostic marker, it is strongly advised
      in the assessment of patients with chronic heart failure undergoing
      cardiopulmonary exercise testing.

PMID- 21883096
TI  - Expression patterns of natural killer receptor genes in inflamed joints and
      peripheral blood of patients with psoriatic arthritis.

PMID- 21883098
TI  - MRI and visual-evoked potentials in partners of multiple sclerosis patients.
AB  - OBJECTIVE: Some epidemiological evidence, particularly concerning the role of
      Epstein Barr Virus implies that multiple sclerosis (MS) may be transmissible and
      if correct, this might be revealed by increased prevalence of MS in cohabiting
      partners. METHODS: We addressed this problem by neurological assessment, visual
      evoked potentials (VEP) and magnetic resonance imaging (MRI) in 112 partners of
      patients with MS in comparison to a control group of 93 individuals with
      clinically non-significant head or neck pain and in comparison to UK prevalence.
      RESULTS: We found one instance of conjugal definite MS. Including this case, VEP
      were abnormal in five instances with either significant delay (n = 3) or
      increased interocular latency difference (IOLD) (n = 2) in partners of MS
      patients thus raising the possibility of subclinical optic nerve demyelination.
      The mean absolute value of IOLD in partners was greater than the value in
      controls (P = 0.033). There were no significant differences in MRI findings
      between the two groups. CONCLUSION: The finding of one conjugal pair and abnormal
      VEP in a further four MS partners could have several explanations. It is
      compatible with the concept of a transmissible agent, although our observations
      could be due to several biases as well as the play of chance alone.

PMID- 21883097
TI  - Tolerability and safety of perampanel: two randomized dose-escalation studies.
AB  - OBJECTIVES: To evaluate, for the first time in patients with epilepsy, the
      tolerability and safety of escalating doses of oral perampanel, a novel,
      selective, non-competitive AMPA antagonist, as adjunctive therapy for refractory
      partial-onset seizures. MATERIALS AND METHODS: Two consecutive, randomized,
      double-blind, dose-escalation studies recruited adults (18-70 years) with
      uncontrolled partial-onset seizures receiving one to three concomitant
      antiepileptic drugs. In study 206, patients were treated for 12 weeks (8-week
      dose-titration, 4-week dose-maintenance) with placebo or perampanel (up to 4
      mg/day, dosed once- or twice-daily). In study 208, patients received placebo or
      perampanel once-daily (up to 12 mg) for 16 weeks (12-week titration, 4-week
      maintenance). RESULTS: Overall, 153 patients were randomized into study 206
      (perampanel twice-daily, n = 51; perampanel once-daily, n = 51; placebo, n = 51).
      Study 208 included 48 patients (perampanel once-daily, n = 38; placebo, n = 10).
      The highest dose in study 206 - 4 mg/day - was well tolerated, with similar
      proportions of patients tolerating once-daily (82.4%) and twice-daily (82.4%)
      perampanel and placebo (82.4%) treatments. In study 208 most patients tolerated
      doses of >= 6 mg perampanel once-daily in a Kaplan-Meier analysis. In both
      studies, the most common adverse events were CNS-related; most were of
      mild/moderate severity. CONCLUSIONS: Perampanel was well tolerated across doses
      of 4-12 mg/day. The studies showed preliminary evidence of efficacy and
      identified doses to be evaluated in larger clinical studies.

PMID- 21883100
TI  - Value of neuropsychological tests, neuroimaging, and biomarkers for diagnosing
      Alzheimer's disease in younger and older age cohorts.
AB  - OBJECTIVES: To examine the influence of age on the value of four techniques for
      diagnosing Alzheimer's disease (AD). DESIGN: Observational cohort study. SETTING:
      Alzheimer's Disease Neuroimaging Initiative. PARTICIPANTS: Individuals with mild
      cognitive impairment (MCI; n = 179), individuals with AD (n = 91), and normal
      controls (n = 105). MEASUREMENTS: Neuropsychological tests, structural magnetic
      resonance imaging (MRI), amyloid-beta and tau in cerebrospinal fluid (CSF), and
      [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) for the diagnosis
      of MCI or AD. MCI was defined according to subjective memory complaints
      corroborated by an informant and an abnormal score on the delayed paragraph
      recall subtest of the Wechsler Memory Scale-Revised, a Mini-Mental State
      Examination score greater than 23, and a Clinical Dementia Rating score of 0.5.
      Participants with AD satisfied National Institute of Neurological and
      Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders
      Association criteria of probable AD. RESULTS: Neuropsychological tests and MRI
      were the most informative techniques, with 84% and 82% correct classifications,
      respectively, and areas under the receiver operating characteristic curve (AUCs)
      of 0.93 (90% confidence interval (CI) = 0.91-0.95) and 0.88 (90% CI = 0.85-0.91).
      FDG-PET and CSF assessments had 76% and 73% correct classifications,
      respectively, (AUC = 0.77, 90% CI = 0.71-0.83; AUC = 0.77, 90% CI = 0.73-0.82).
      These figures increased slightly when the techniques were combined. All analyses
      were repeated for the younger (<75) and older (>= 75) halves of the sample. FDG
      PET and CSF assessment were substantially less informative in the older cohort,
      and they did not add diagnostic information when all techniques were combined.
      CONCLUSIONS: Structural MRI and neuropsychological assessment are diagnostic
      methods of first choice if AD is suspected. CSF and FDG-PET add little to these
      diagnostic techniques, especially in older adults.

PMID- 21883099
TI  - Cannabis use and age at onset of symptoms in subjects at clinical high risk for
      psychosis.
AB  - OBJECTIVE: Numerous studies have found a robust association between cannabis use
      and the onset of psychosis. Nevertheless, the relationship between cannabis use
      and the onset of early (or, in retrospect, prodromal) symptoms of psychosis
      remains unclear. The study focused on investigating the relationship between
      cannabis use and early and high-risk symptoms in subjects at clinical high risk
      for psychosis. METHOD: Prospective multicenter, naturalistic field study with an
      18-month follow-up period in 245 help-seeking individuals clinically at high
      risk. The Composite International Diagnostic Interview was used to assess their
      cannabis use. Age at onset of high risk or certain early symptoms was assessed
      retrospectively with the Interview for the Retrospective Assessment of the Onset
      of Schizophrenia. RESULTS: Younger age at onset of cannabis use or a cannabis use
      disorder was significantly related to younger age at onset of six symptoms (0.33
      < r(s) < 0.83, 0.004 < P < 0.001). Onset of cannabis use preceded symptoms in
      most participants. CONCLUSION: Our results provide support that cannabis use
      plays an important role in the development of psychosis in vulnerable
      individuals. Cannabis use in early adolescence should be discouraged.

PMID- 21883101
TI  - Age differences in primary prevention implantable cardioverter-defibrillator use
      in U.S. individuals.
AB  - OBJECTIVES: To estimate the potentially inappropriate use of implantable
      cardioverter-defibrillator ICDs in older U.S. adults. DESIGN: Retrospective
      study. SETTING: The National Cardiovascular Data ICD Registry. PARTICIPANTS:
      Forty-four thousand eight hundred five individuals in the National Cardiovascular
      Data's ICD Registry(TM) who had received ICDs for primary prevention from January
      2006 to December 2008. Individuals with a prior myocardial infarction and
      ejection fraction less than 30% were included. MEASUREMENTS: Mortality risk was
      categorized using the Multicenter Automatic Defibrillator Implantation (MADIT) II
      risk-stratification system. Low-risk and very-high-risk individuals were
      considered potentially inappropriate recipients. RESULTS: Of 44,805 individuals,
      67% (n = 29,893) were aged 65 and older, of whom 51% were aged 75 and older. A
      significant proportion of ICD recipients had a low risk of death (16%, n = 6,969)
      or very high risk of nonarrhythmic death (8%, n = 3,693). Potentially
      inappropriate ICD use was 10% in those aged 75 and older, much less than in
      younger groups (40%, <65; 21%, 65-74, P < .001). Although age was associated with
      a high risk of nonarrhythmic death, its influence was markedly attenuated after
      adjusting for comorbidities and timing of ICD implantation (odds ratio = 1.02,
      95% confidence interval = 1.02-1.03, P < .001). CONCLUSION: Potentially
      inappropriate ICD use appears significantly less--and at modest rates--in older
      Americans than in younger age groups. Overall, almost one-quarter of individuals
      may have received ICDs inappropriately based on their risk of death. Physicians
      appear to be conservatively referring older adults and wisely deferring those
      with high comorbid burden.

PMID- 21883102
TI  - Proton pump inhibitor discontinuation in long-term care.
AB  - OBJECTIVES: To determine factors associated with proton pump inhibitor (PPI)
      discontinuation in long-term care. DESIGN: Retrospective cohort analysis.
      SETTING: Veterans Affairs (VA) long-term care facilities. PARTICIPANTS: Veterans
      admitted for nonhospice care in 2005 with a length of stay of 7 days or more who
      were prescribed a PPI within 7 days of admission (N = 10,371). MEASUREMENTS:
      Prescribed medications and comorbidities were determined from VA pharmacy and
      administrative databases and functional status from Minimum Data Set records.
      Associations between participant characteristics and PPI discontinuation were
      determined using Cox proportional hazard ratios (HRs), censoring at death,
      discharge, or 180 days after admission. RESULTS: Participants were predominantly
      male (97%) and had a median age of 73 (interquartile range 60-81). There were
      2,749 (27%) PPI discontinuations; 43% of these occurred within 28 days of
      admission. Hospitalizations (HR = 1.22, 95% confidence interval (CI) = 1.01
      1.46), preadmission PPI use (HR = 1.35, 95% CI = 1.16-1.56), and lowest
      functional status (HR = 1.22, 95% CI = 1.03-1.45) were associated with early PPI
      discontinuation in adjusted models. Participants with gastric acid-related
      disease (HR = 0.53, 95% CI 0.46-0.61), diabetes mellitus (HR = 0.82, 95% CI 0.72
      0.94), and those who were prescribed six or more medications (6-7 medications, HR
      = 0.78, 95% CI = 0.66-0.92; 8-10 medications, HR = 0.64, 95% CI = 0.54-0.76; >=
      11 medications 0.51, 95% CI = 0.42-0.62) were less likely to have early
      discontinuation. No PPI discontinuer had PPIs resumed during the study, and few
      (9%) had histamine-2 receptor antagonist substitutions. CONCLUSION: Although
      there may be clinical uncertainty regarding PPI discontinuation, more than one
      quarter of participants prescribed a PPI upon admission to long-term care had it
      discontinued within 180 days. Targeting individuals prescribed PPIs for
      medication appropriateness review may reduce prescribing of potentially
      nonindicated medications.

PMID- 21883103
TI  - A 2-year follow-up of a lifestyle physical activity versus a structured exercise
      intervention in older adults.
AB  - OBJECTIVES: To evaluate the long-term effects of a lifestyle intervention and a
      structured exercise intervention on physical fitness and cardiovascular risk
      factors in older adults. DESIGN: Controlled trial with randomization between the
      intervention groups. SETTING: Belgium, Vlaams-Brabant. PARTICIPANTS: One hundred
      eighty-six sedentary but healthy men and women aged 60 to 83. INTERVENTIONS:
      Participants in the lifestyle intervention were stimulated to integrate physical
      activity into their daily routines and received an individualized home-based
      program supported by telephone calls. The structured intervention consisted of
      three weekly supervised sessions in a fitness center. Both interventions lasted
      11 months and focused on endurance, strength, flexibility, and postural and
      balance exercises. MEASUREMENTS: Cardiorespiratory fitness, muscular strength,
      functional performance, blood pressure, and body composition were measured before
      (pretest), at the end (11 months, posttest), and 1 year after the end (23 months,
      follow-up) of the interventions. RESULTS: The results from pretest to posttest
      have already been published. The current study analyzed the results from posttest
      to follow-up. There was a decrease in cardiorespiratory fitness, muscular
      fitness, and functional performance from posttest to follow-up in the structured
      intervention group but not in the control group or the lifestyle intervention
      group. At 23 months, participants in both groups still showed improvements in
      cardiorespiratory fitness. In addition, the structured group showed long-term
      improvements in muscular fitness, whereas the lifestyle group showed long-term
      improvements in functional performance. No long-term effects were found for blood
      pressure or body composition. CONCLUSION: These results highlight the potential
      of a structured fitness center-based intervention and a home-based lifestyle
      intervention in the battle against inactivity in older adults. Lifestyle programs
      are especially valuable because they require fewer resources and less time from
      health institutions and health practitioners.

PMID- 21883104
TI  - Improving internal medicine residents' falls assessment and evaluation: an
      interdisciplinary, multistrategy program.
AB  - Falls are a major problem in older adults, and physicians receive inadequate
      training in falls evaluation. A multicomponent program (lecture, academic
      detailing, and case studies) was implemented to enhance medical residents'
      knowledge, skills, decisions, and interventions made about falls as part of a
      larger project to improve assessment and care of older adults. Electronic medical
      record (EMR) template modifications provided cues and reminders, decision
      support, and documentation into the visit note. Nursing staff and the EMR
      prompted residents to evaluate patients with a history of falls. Knowledge and
      confidence were assessed using a pre- and postintervention questionnaire, and an
      attending physician assessed skills by direct observation of the Timed Up and Go
      Test (TUG). Effect on clinical actions was assessed using the EMR database.
      Participation in training of faculty and staff was high. Over the 3-month
      intervention period, an attending physician reviewed the detailing sheet
      outlining important points of the training with 86% of residents, and 64%
      demonstrated a TUG to an attending physician. Of 895 older adults seen, 15% (134)
      had a positive screen for falls, of whom 92% (123) had an EMR falls template
      completed, and 42% (56) had a TUG performed. Of the patients evaluated with the
      TUG, 53% (29) failed. A review of charts for patients who failed the screen or
      TUG revealed that the majority had special circumstances limiting their
      participation, even after a physical therapy evaluation. Education and system
      changes facilitated improvements in resident knowledge, skill, self-efficacy, and
      clinical action in screening, evaluating, and managing falls in older adults.

PMID- 21883105
TI  - Avoidability of hospital transfers of nursing home residents: perspectives of
      frontline staff.
AB  - OBJECTIVES: To describe nursing home (NH) staff perceptions of avoidability of
      hospital transfers of NH residents. DESIGN: Mixed methods qualitative and
      quantitative analysis of 1,347 quality improvement (QI) review tools completed by
      staff at 26 NHs and transcripts of conference calls. SETTING: Twenty-six NHs in
      three states participating in the Interventions to Reduce Acute Care Transfers
      (INTERACT II) QI project. PARTICIPANTS: Site coordinators and staff who
      participated in project orientation and conference calls and completed QI tools.
      MEASUREMENTS: NH and hospitalization data collected for the INTERACT II project.
      An interprofessional team coded and quantified reasons for hospital transfer on
      1,347 QI review tools. RESULTS: Staff rated 76% of the transfers in the QI review
      tools as not avoidable. Common reasons for transfers rated as unavoidable were
      acute change in resident status, family insistence, and physician order for
      transfer. These same reasons were given for transfers rated as avoidable.
      Avoidable ratings were associated with a broader set of reasons and
      recommendations for improvement, including earlier identification and management
      of changes in clinical status, earlier discussion with family members about
      advance directives, and more-comprehensive communication with physicians. NHs
      that were more actively engaged in the INTERACT II interventions rated more
      transfers as avoidable. Percentage of transfers rated avoidable was not
      correlated with change in hospitalization rates. CONCLUSION: NH staff rated fewer
      hospital transfers as avoidable than published estimates. Greater attention to
      the complex array of reasons that staff provide for hospital transfer should be
      considered in strategies to reduce avoidable hospitalizations of NH residents.

PMID- 21883106
TI  - Measurement of organ structure and function enhances understanding of the
      physiological basis of frailty: the Cardiovascular Health Study.
AB  - OBJECTIVES: To determine whether disease burden is associated with frailty
      independent of diagnosed chronic disease and whether physiological measurements
      provide greater understanding of the etiology of frailty. DESIGN: Cross
      sectional. SETTING: Community. PARTICIPANTS: Two thousand four hundred thirty
      seven participants in the Cardiovascular Health Study, 1992/93 examination (mean
      age 74.8 +/- 4.8, 43.4% male, 95.8% white). MEASUREMENTS: Disease burden and
      frailty were tabulated using 10-point scales (0 = healthy, 10 = unhealthy).
      Disease burden was the sum of measurements characterizing the vasculature, brain,
      kidneys, lungs, and glucose metabolism. Frailty was assessed using the frailty
      index reported by Fried. Multivariate linear models were used to determine the
      association between disease burden (predictor) and frailty (outcome). RESULTS:
      Unadjusted, 1-point-higher disease burden was associated with a 0.28-point-higher
      frailty score (P < .001). White matter grade, forced vital capacity, and cystatin
      C were particularly strongly and significantly associated with frailty. Disease
      burden attenuated the association between frailty and age by 29%, and disease
      burden and age had similar associations with frailty. Disease burden attenuated
      the association between frailty and fibrinogen, Factor VIII, and C-reactive
      protein by 32%, 56%, and 83%, respectively. Frailty was associated with diagnosed
      depression, stroke, cognitive impairment, arthritis, and pulmonary disease but
      not coronary heart disease, diabetes mellitus, or kidney disease in the presence
      of a summary of disease burden. In the adjusted model, disease burden remained
      significantly associated with frailty (beta = 0.11, P < .001). CONCLUSION:
      Disease burden was independently and significantly associated with frailty. These
      results emphasize that typically unrecognized physiological changes may
      contribute significantly to frailty.

PMID- 21883107
TI  - Plasma klotho and cardiovascular disease in adults.
AB  - OBJECTIVES: To determine whether plasma klotho, a recently discovered hormone
      that has been implicated in atherosclerosis, is related to prevalent
      cardiovascular disease (CVD) in adults. DESIGN: Cross-sectional. SETTING:
      Population-based sample of adults residing in Tuscany, Italy. PARTICIPANTS: One
      thousand twenty-three men and women aged 24 to 102 participating in the
      Invecchiare in Chianti (InCHIANTI) study. MEASUREMENTS: Anthropometric measures,
      plasma klotho, fasting plasma total, high-density lipoprotein cholesterol (HDL
      C), triglycerides, glucose, creatinine, C-reactive protein (CRP). Clinical
      measures: medical assessment, diabetes mellitus, hypertension, coronary heart
      disease, heart failure, stroke, peripheral artery disease, cancer, chronic kidney
      disease. Logistic regression models were used to examine the relationship between
      plasma klotho and prevalent CVD. RESULTS: Of 1,023 participants, 259 (25.3%) had
      CVD. Median (25th, 75th percentile) plasma klotho concentrations were 676 pg/mL
      (530, 819 pg/mL). Plasma klotho was correlated with age (correlation coefficient
      (r) = -0.14, P < .001), HDL-C (r = 0.11, P<.001), and CRP (r = -0.10, P < .001)
      but not systolic blood pressure, fasting plasma glucose, or renal function.
      Plasma klotho age-adjusted geometric means were 626 pg/mL (95% confidence
      interval (CI) = 601-658 pg/mL) in participants with CVD and 671 pg/mL (95% CI =
      652-692 pg/mL) in those without CVD (P = .001). Adjusting for traditional
      cardiovascular risk factors (age, sex, smoking, total cholesterol, HDL-C,
      systolic blood pressure, and diabetes mellitus), log plasma klotho was associated
      with prevalent CVD (odds ratio per 1 standard deviation increase = 0.85, 95% CI =
      0.72-0.99). CONCLUSION: In community-dwelling adults, higher plasma klotho
      concentrations are independently associated with a lower likelihood of having
      CVD.

PMID- 21883108
TI  - Trends in use of high-risk medications for older veterans: 2004 to 2006.
AB  - OBJECTIVES: To examine the change in use of high-risk medications for the elderly
      (HRME), as defined by the National Committee on Quality Assurance's Healthcare
      Effectiveness Data and Information Set (HEDIS) quality measure (HEDIS HRME), by
      older outpatient veterans over a 3-year period and to identify risk factors for
      HEDIS HRME exposure overall and for the most commonly used drug classes. DESIGN:
      Longitudinal retrospective database analysis. SETTING: Outpatient clinics within
      the Department of Veterans Affairs (VA). PARTICIPANTS: Veterans aged 65 by
      October 1, 2003, and who received VA care at least once each year until September
      30, 2006. MEASUREMENTS: Rates of use of HEDIS HRME overall and according to
      specific drug classes each year from fiscal year 2004 (FY04) to FY06. RESULTS: In
      a cohort of 1,567,467, high-risk medication exposure fell from 13.1% to 12.3%
      between FY04 and FY06 (P<.001). High-risk antihistamines (e.g., diphenhydramine),
      opioid analgesics (e.g., propoxyphene), skeletal muscle relaxants (e.g.,
      cyclobenzaprine), psychotropics (e.g., long half-life benzodiazepines), endocrine
      (e.g., estrogen), and cardiac medications (e.g., short-acting nifedipine) had
      modest but statistically significant (P<.001) reductions (range -3.8% to -16.0%);
      nitrofurantoin demonstrated a statistically significant increase (+36.5%;
      P<.001). Overall HEDIS HRME exposure was more likely for men, Hispanics, those
      receiving more medications, those with psychiatric comorbidity, and those without
      prior geriatric care. Exposure was lower for individuals exempt from copayment.
      Similar associations were seen between ethnicity, polypharmacy, psychiatric
      comorbidity, access-to-care factors, and use of individual HEDIS HRME classes.
      CONCLUSION: HEDIS HRME drug exposure decreased slightly in an integrated
      healthcare system. Risk factors for exposure were not consistent across drug
      groups. Future studies should examine whether interventions to further reduce
      HEDIS HRME use improve health outcomes.

PMID- 21883109
TI  - Meaningful improvement in gait speed in hip fracture recovery.
AB  - OBJECTIVES: To estimate meaningful improvements in gait speed observed during
      recovery from hip fracture and to evaluate the sensitivity and specificity of
      gait speed changes in detecting change in self-reported mobility. DESIGN:
      Secondary longitudinal data analysis from two randomized controlled trials
      SETTING: Twelve hospitals in the Baltimore, Maryland, area. PARTICIPANTS: Two
      hundred seventeen women admitted with hip fracture. MEASUREMENTS: Usual gait
      speed and self-reported mobility (ability to walk 1 block and climb 1 flight of
      stairs) measured 2 and 12 months after fracture. RESULTS: Effect size-based
      estimates of meaningful differences were 0.03 for small differences and 0.09 for
      substantial differences. Depending on the anchor (stairs vs walking) and method
      (mean difference vs regression), anchor-based estimates ranged from 0.10 to 0.17
      m/s for small meaningful improvements and 0.17 to 0.26 m/s for substantial
      meaningful improvement. Optimal gait speed cutpoints yielded low sensitivity
      (0.39-0.62) and specificity (0.57-0.76) for improvements in self-reported
      mobility. CONCLUSION: Results from this sample of women recovering from hip
      fracture provide only limited support for the 0.10-m/s cut point for substantial
      meaningful change previously identified in community-dwelling older adults
      experiencing declines in walking abilities. Anchor-based estimates and cut points
      derived from receiver operating characteristic curve analysis suggest that
      greater improvements in gait speed may be required for substantial perceived
      mobility improvement in female hip fracture patients. Furthermore, gait speed
      change performed poorly in discriminating change in self-reported mobility.
      Estimates of meaningful change in gait speed may differ based on the direction of
      change (improvement vs decline) or between patient populations.

PMID- 21883110
TI  - Psychoactive medications and crash involvement requiring hospitalization for
      older drivers: a population-based study.
AB  - OBJECTIVES: To determine the association between psychoactive medications and
      crash risk in drivers aged 60 and older. DESIGN: Retrospective population-based
      case-crossover study. SETTING: A database study that linked the Western
      Australian Hospital Morbidity Data System and the Pharmaceutical Benefits Scheme.
      PARTICIPANTS: Six hundred sixteen individuals aged 60 and older who were
      hospitalized as the result of a motor vehicle crash between 2002 and 2008 in
      Western Australia. MEASUREMENTS: Hospitalization after a motor vehicle crash.
      RESULTS: Greater risk for a hospitalization crash was found for older drivers
      prescribed benzodiazepines (odds ratio (OR)=5.3, 95% confidence interval (CI)=3.6
      7.8, P<.001), antidepressants (OR=1.8, 95% CI=1.0-3.3, P=.04), and opioid
      analgesics (OR=1.5, 95% CI=1.0-2.3, P=.05). Crash risk was significantly greater
      in men prescribed a benzodiazepine (OR=6.2, 95% CI=3.2-12.2, P<.001) or an
      antidepressant (OR=2.7, 95% CI=1.1-6.9, P=.03). Women prescribed benzodiazepines
      (OR=4.9, 95% CI=3.1-7.8, P<.001) or opioid analgesics (OR=1.8, 95% CI=1.1-3.0,
      P=.03) also had a significantly greater crash risk. Subgroup analyses further
      suggested that drivers with (OR=4.0, 95% CI=2.9-8.1, P<.001) and without (OR=6.0,
      95% CI=3.8-9.5, P<.001) a chronic condition who were prescribed benzodiazepines
      were at greater crash risk. Drivers with a chronic condition taking
      antidepressants (OR=3.4, 95% CI=1.3-8.5, P=.01) also had a greater crash risk.
      CONCLUSION: Psychoactive medication usage was associated with greater risk of a
      motor vehicle crash requiring hospitalization in older drivers.

PMID- 21883111
TI  - Impaired frontal executive function and predialytic chronic kidney disease.
AB  - OBJECTIVES: To investigate the nature of frontal dysfunction associated with
      chronic kidney disease (CKD) in people without stroke or depressive disorders.
      DESIGN: Cross-sectional. SETTING: Community based. PARTICIPANTS: Five hundred
      twenty-nine community-dwelling participants. MEASUREMENTS: Participants with CKD
      were classified into one of three diagnostic groups based on their estimated
      glomerular filtration rate (eGFR): normal (>= 60.0 mL/min per 1.73 m(2)), mild
      CKD (45.0-59.9 mL/min per 1.73 m(2)), or moderate to severe CKD (<45.0 mL/min per
      1.73 m(2)). Cognitive function was assessed using the Korean version of the
      Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological
      Assessment Battery, lexical fluency, digit span test, and the 64-card Wisconsin
      Card Sorting Test. RESULTS: Perseverative responses and perseverative errors were
      significantly more prevalent in the group with moderate to severe CKD than in
      those without CKD and those with mild CKD. The mean number of perseverative
      responses was 28.6 +/- 16.9 in participants with moderate to severe CKD, 19.0 +/-
      11.4 in those with mild CKD, and 17.1 +/- 10.6 in those without CKD (P < .001,
      ANCOVA). The mean number of perseverative errors was 23.1 +/- 12.3 in
      participants with moderate to severe CKD, 16.2 +/- 8.3 in those with mild CKD,
      and 14.8 +/- 7.8 in those without CKD (P < .001, analysis of covariance). The
      odds ratios in the fully adjusted model for the presence of moderate to severe
      CKD for perseverative responses and perseverative errors were 4.82 (95%
      confidence interval (CI) = 2.14-10.85, P < .001) and 5.01 (95% CI = 2.22-11.28,
      P<.001), respectively. CONCLUSION: Frontal dysfunction, particularly
      perseverative errors and responses, was associated with moderate to severe CKD in
      the population studied.

PMID- 21883112
TI  - Aging and left ventricular mass and function in people with end-stage renal
      disease.
AB  - OBJECTIVES: To identify the main age-related factors responsible for
      cardiomyopathy in people with end-stage renal disease (ESRD). DESIGN: Cross
      sectional. SETTING: Dialysis unit. PARTICIPANTS: Two hundred fifty-four
      individuals undergoing chronic dialysis. MEASUREMENTS: Left ventricular (LV)
      systolic function (assessed according to midwall fractional shortening (mwFS))
      and LV mass index (LVMI). RESULTS: At echocardiography, 196 (77%) participants
      displayed LV hypertrophy (LVH) and 123 (48%) had LV systolic dysfunction. On
      univariate analysis, age was related directly to LVMI (correlation coefficient
      (r)=0.33, P<.001) and inversely to mwFS (r=-0.23, P<.001) and a 10-year increase
      in age was associated with 4.2-g/m(2.7) greater LVMI and 0.5% lower mwFS.
      Albumin, pulse pressure, cardiovascular comorbidities, and C-reactive protein
      were age-related risk factors for LVMI and mwFS, whereas hemoglobin was an age
      dependent risk factor only for LVMI and heart rate and diabetes mellitus only for
      mwFS. After adjusting for age-related risk factors, the predictive value of age
      for cardiomyopathy was substantially less (-67%) and the age-dependent
      variability in LVMI and mwFS was much attenuated (-61%), and neither was
      significant. CONCLUSION: This study suggests that in people with ESRD, the
      relationship between age and cardiomyopathy is largely dependent on age-related
      risk factors and that interventions focused on modifiable risk factors linked to
      age (e.g., malnutrition and inflammation) could attenuate the detrimental effect
      of aging on cardiovascular risk in the dialysis population.

PMID- 21883114
TI  - Association between insomnia symptoms and weight change in older women: caregiver
      -study of osteoporotic fractures study.
AB  - OBJECTIVES: To determine whether self-reported insomnia symptoms were associated
      with weight change in older women and whether caregiving, comorbidities, sleep
      medication, or stress modified this association. DESIGN: One-year prospective
      study conducted in four communities from 1999 to 2003 nested within a larger
      cohort study. SETTING: Home-based interviews. PARTICIPANTS: Nine hundred eighty
      eight participants (354 caregivers and 634 noncaregivers) from the Caregiver-
      Study of Osteoporotic Fractures. MEASUREMENTS: Self-reported insomnia symptoms in
      the previous month: trouble falling asleep, trouble staying asleep, and waking
      early and having trouble getting back to sleep. Weight was measured at baseline
      and 12 months. RESULTS: The average weight change was -1.9 +/- 7.8 pounds.
      Trouble staying asleep was significantly associated with an average weight loss
      of 1.3 pounds (P = .03) in multivariable analyses. Neither of the other insomnia
      symptoms was associated with weight change. Use of sleep medications modified the
      association between trouble falling asleep (interaction term P = .03) and weight
      change. Insomnia symptoms were associated with weight loss only in women not
      taking sleep medications. Neither caregiving status, presence of multiple
      comorbidities, nor stress modified the association. CONCLUSION: Trouble staying
      asleep was associated with weight loss over 12 months in older women.
      Practitioners should inquire about sleep habits of patients presenting with
      weight loss, because this may identify a marker of declining health and may be a
      factor that can be modified.

PMID- 21883113
TI  - Inappropriate medication use in older adults undergoing surgery: a national
      study.
AB  - OBJECTIVES: To determine the prevalence and factors associated with use of
      potentially inappropriate medications (PIMs) in older adults undergoing surgery.
      DESIGN: Retrospective cohort study. SETTING: Three hundred seventy-nine acute
      care hospitals participating in the nationally representative Perspective
      database (2006-2008). PARTICIPANTS: Individuals aged 65 and older undergoing
      major inpatient gastrointestinal, gynecological, urological, and orthopedic
      surgery (N=272,351). MEASUREMENTS: Medications were classified as PIMs using
      previously published criteria defining 33 medications deemed potentially
      inappropriate in people aged 65 and older. Information about participant and
      provider characteristics and administration of PIMs was obtained from hospital
      discharge file data. Logistic regression techniques were used to examine factors
      associated with use of PIMs in the perioperative period. RESULTS: One-quarter of
      participants received at least one PIM during their surgical admission.
      Meperidine was the most frequently prescribed PIM (37,855, 14% of participants).
      In adjusted analysis, PIM use was less likely as age advanced (adjusted odds
      ratio (AOR)=0.98 per year of age, 95% confidence interval (CI)=0.97-0.98) and in
      men (AOR=0.83, 95% CI=0.81-0.85). PIMs were more likely to be prescribed to
      participants cared for by orthopedic surgeons than for those cared for by general
      surgeons (AOR=1.22, 95% CI=1.08-1.40). Participants undergoing surgery in the
      West (AOR=1.79, 95% CI=1.02-3.16) and South (AOR=2.24, 95% CI=1.38-3.64) were
      more likely to receive a PIM than those in the Northeast. CONCLUSION: Receipt of
      PIMs in older adults undergoing surgery is common and varies widely between
      providers and geographic regions and according to participant characteristics.
      Interventions aimed at reducing the use of PIMs in the perioperative period
      should be considered in quality improvement efforts.

PMID- 21883115
TI  - Interleukin-6, C-reactive protein, and tumor necrosis factor-alpha as predictors
      of mortality in frail, community-living elderly individuals.
AB  - To investigate whether interleukin-6 (IL-6), C-reactive protein (CRP) and tumor
      necrosis factor-alpha (TNF-alpha) protein levels predict all-cause mortality in
      older persons living in the community. DESIGN: Prospective cohort study. SETTING:
      Data were from the Aging and Longevity Study in the Sirente Geographic Area, a
      prospective cohort study. PARTICIPANTS: Individuals aged 80 and older living in
      an Italian mountain community (N = 362). MEASUREMENTS: Participants were
      classified according to the median value of the three inflammation markers (IL-6,
      2.08 pg/mL; TNF-alpha, 1.43 pg/mL; CRP, 3.08 mg/L). A composite summary score of
      inflammation was also created. The main outcome was risk of death after 4 years
      of follow-up. RESULTS: One hundred fifty deaths occurred during 4 years of follow
      up. In the unadjusted model, high levels of each of the three markers were
      associated with greater mortality. After adjusting for potential confounders,
      high levels of IL-6 (hazard ratio (HR) = 2.18, 95% confidence interval (CI) =
      1.29-3.69) and CRP (HR = 2.58, 95% CI = 1.52-4.40) were associated with a
      significantly greater risk of death, whereas the association between TNF-alpha
      protein levels and mortality was no longer significant (HR = 1.26, 95% CI = 0.74
      2.15). The composite summary score of inflammation was strongly associated with
      mortality, with the highest risk estimated for individuals with all three
      inflammatory markers above the median. CONCLUSION: Low levels of inflammatory
      markers are associated with better survival in older adults, independent of age
      and other clinical and functional variables.

PMID- 21883116
TI  - Cost-effectiveness of oral bisphosphonates for osteoporosis at different ages and
      levels of life expectancy.
AB  - OBJECTIVES: To evaluate the cost-effectiveness of oral bisphosphonate therapy for
      osteoporosis in women at different ages and life expectancies. DESIGN: A Markov
      model was used to analyze oral bisphosphonate treatment for 5 years compared to
      no intervention. Women at each age were divided into life expectancy quartiles:
      the lowest 1% to 25% (sickest group), the two middle 26% to 75% (average health
      group), and the highest 76% to 100% of life expectancy (healthiest group).
      Simulations were performed for hypothetical cohorts at 5-year intervals with
      starting ages between 50 and 90 and for each life expectancy group and followed
      for up to 100 years or until death. Data sources included published fracture
      rates, costs, utility values, and mortality risks. SETTING: Computer simulation
      using a societal perspective. PARTICIPANTS: Hypothetical cohort of women with
      various life expectancies beginning osteoporosis treatment between the age of 50
      and 90 years. MEASUREMENTS: Cost per quality-adjusted life years (QALY) gained
      for 5 years of bisphosphonate therapy compared to no treatment. Cost
      effectiveness was defined at a willingness-to-pay of $50,000. RESULTS: In the
      healthiest group, all costs were less than $18,000 per QALY. In the median
      quartiles of life expectancy, lifetime costs per QALY were less than $27,000 for
      patients at all ages; treatment became cost-saving at a starting age of 75 and
      remained so through a starting age of 85. Even in the sickest group, although
      osteoporosis treatment was not cost-saving, it remained cost-effective through a
      starting age of 90 with lifetime costs of less than $43,000 per QALY. CONCLUSION:
      Treatment with an oral bisphosphonate for 5 years was cost-effective for all
      women, regardless of quartile of life expectancy. Advanced age should not prevent
      consideration of osteoporosis treatment based on cost effectiveness, and
      strategies to improve care, such as nurse-led screening programs or electronic
      medical record tools, are needed.

PMID- 21883117
TI  - Physician follow-up visits after acute care hospitalization for elderly Medicare
      beneficiaries discharged to noninstitutional settings.
AB  - The purpose of this study was to assess the effect of posthospital physician
      follow-up on readmissions in older adults. Physician follow-up visits after
      discharge have been promoted as a way to improve outcomes and reduce
      readmissions, but the evidence base for this recommendation is limited. A
      retrospective analysis of data from the Medicare Current Beneficiary Survey
      (MCBS) was conducted for 2001 to 2003. Data were extracted on elderly Medicare
      beneficiaries with an index hospitalization in 2002, and physician follow-up
      visits and readmissions within 90 days of discharge were identified. Analysis was
      conducted with multivariable logistic regression modeling to assess the
      independent effect on 90-day readmission of any physician follow-up, timing of
      physician follow-up, and follow-up with only primary care physicians. A
      generalized linear model was used to assess the effect of physician follow-up on
      total health expenditures. The analytical sample included 326 beneficiaries; 79%
      had a physician follow-up visit within 90 days, and 28% were readmitted within 90
      days. In multivariable modeling, physician follow-up was negatively associated
      with 90-day readmissions (odds ratio=0.23, 95% confidence interval=0.13-0.43).
      Follow-up visits were protective against readmissions regardless of timing of
      visit and when restricted to those by primary care physicians. Having a follow-up
      visit was associated with approximately $10,000 lower annual health expenditures.
      In conclusion, physician follow-up protects against readmission after adjusting
      for important covariates and is associated with significantly lower expenditures.
      Future efforts should ensure that patients have adequate physician follow-up.

PMID- 21883118
TI  - Contribution of multiple chronic conditions to universal health outcomes.
AB  - OBJECTIVES: To determine the relative effect of five chronic conditions on four
      representative universal health outcomes. DESIGN: Cross-sectional. SETTING:
      Cardiovascular Health Study. PARTICIPANTS: Five thousand two hundred and ninety
      eight community-living participants aged 65 and older. MEASUREMENTS: Multiple
      regression and Cox models were used to determine the effect of heart failure
      (HF), chronic obstructive pulmonary disease (COPD), osteoarthritis, depression,
      and cognitive impairment on self-rated health, 12 basic and instrumental
      activities of daily living (ADLs and IADLs), six-item symptom burden scale, and
      death. RESULTS: Each condition adversely affected self-rated health (P < .001)
      and ADLs and IADLs (P < .001). For example, persons with HF performed 0.70 +/-
      0.08 fewer ADLs and IADLs than those without; persons with depression and persons
      with cognitive impairment performed 0.59 +/- 0.04 and 0.58 +/- 0.06 fewer
      activities, respectively, than those without these conditions. Depression, HF,
      COPD, and osteoarthritis were associated with 1.18 +/- 0.04, 0.40 +/- 0.08, 0.40
      +/- 0.05, and 0.57 +/- 0.03 more symptoms, respectively, in individuals with
      these conditions than in those without. HF (hazard ratio (HR) = 2.84, 95%
      confidence interval (CI) = 1.97-4.10), COPD (2.62, 95% CI = 1.94-3.53), cognitive
      impairment (2.05, 95% CI = 1.47-2.85), and depression (1.47, 95% CI = 1.08-2.01)
      were each associated with death within 2 years. Several paired combinations of
      conditions had synergistic effects on ADLs and IADLs. For example, individuals
      with HF plus depression performed 2.0 fewer activities than persons with neither
      condition, versus the 1.3 fewer activities expected from adding the effects of
      the two conditions together. CONCLUSION: Universal health outcomes may provide a
      common metric for measuring the effects of multiple conditions and their
      treatments. The varying effects of the conditions across universal outcomes could
      inform care priorities.

PMID- 21883119
TI  - Cortisol, insulin, and glucose and the risk of delirium in older adults with hip
      fracture.
AB  - OBJECTIVES: To determine the relationship between perioperative delirium and
      cortisol, glucose, and insulin in older adults acutely admitted for hip fracture.
      DESIGN: Prospective cohort study. SETTING: Tertiary university center.
      PARTICIPANTS: Consecutive individuals aged 65 and older acutely admitted for hip
      fracture were invited to participate. MEASUREMENTS: All participants were
      repeatedly examined to determine presence and severity of delirium. Blood samples
      for cortisol, glucose, and insulin were drawn at 11:00 a.m. Differences in
      characteristics of participants with and without delirium were evaluated using t
      tests and Mann-Whitney tests. A logistic regression analysis was performed to
      correct for other important risk factors for delirium. RESULTS: One hundred forty
      three participants, 70 (49%) with delirium and 73 (51%) without, were included.
      In univariate analyses, there was a trend toward higher cortisol levels (odds
      ratio = 1.003 (95% confidence interval = 1.001-1.004, P = .004), but this
      association was not statistically significant after multivariable analysis and
      may reflect an association between high cortisol and preexisting cognitive and
      functional impairment, and there was no association with insulin or glucose
      levels. Adjusting for sex and prefracture cognitive and functional impairment
      made the trend with cortisol and delirium statistically nonsignificant.
      CONCLUSION: Delirium in older adults acutely admitted for hip fracture may be
      linked with higher cortisol concentrations, but it may be that this association
      reflects an association between higher cortisol and preexisting cognitive and
      functional impairment.

PMID- 21883121
TI  - Effect of ethnicity and body mass index on the distance from skin to lumbar
      epidural space in parturients.
AB  - With the current prevalence of obesity and trends in ethnic diversity amongst
      parturients in UK maternity units, we performed a prospective, observational
      study to establish the effect of ethnicity and body mass index on the distance
      from skin to epidural space in parturients. A total of 1210 parturients
      participated in this study. The mean (SD) distance from skin to lumbar epidural
      space was 5.4 (1.1) cm. When tested in a multiple regression model, both body
      mass index and ethnicity significantly influenced the distance from skin to
      lumbar epidural space in parturients. The distance from skin to lumbar epidural
      space amongst ethnic groups differed at any given body mass index. It was
      significantly greater in Black/British Black and White parturients compared with
      their Asian and Chinese counterparts. You can respond to this article at
      http://www.anaesthesiacorrespondence.com.

PMID- 21883122
TI  - Insertion of six different supraglottic airway devices whilst wearing chemical,
      biological, radiation, nuclear-personal protective equipment: a manikin study.
AB  - Six different supraglottic airway devices: CombitubeTM, laryngeal mask airway,
      intubating laryngeal mask airway (FastrachTM), i-gelTM, Laryngeal TubeTM and Pro
      SealTM laryngeal mask airway were assessed by 58 paramedic students for speed and
      ease of insertion in a manikin, whilst wearing either chemical, biological,
      radiation, nuclear-personal protective equipment (CBRN-PPE) or a standard
      uniform. All devices took significantly longer to insert when wearing CBRN-PPE
      compared with standard uniform (p < 0.001). In standard uniform, insertion time
      was shorter than 45 s in 90% of attempts for all devices except the Combitube,
      for which 90% of attempts were completed by 53 s. Whilst wearing CBRN-PPE the i
      gel was the fastest device to insert with a mean (SD (95% CI)) insertion time of
      19 (8 (17-21))s, p < 0.001, with the Combitube the slowest with mean (65 (23 (59
      71))s. Wearing of CBRN-PPE has a negative impact on supraglottic airway insertion
      time.

PMID- 21883120
TI  - Effect of chronic disease-related symptoms and impairments on universal health
      outcomes in older adults.
AB  - OBJECTIVES: To determine the extent to which disease-related symptoms and
      impairments, which constitute measures of disease severity or targets of therapy,
      account for the associations between chronic diseases and universal health
      outcomes. DESIGN: Cross-sectional. SETTING: The Cardiovascular Health Study (CHS)
      and the Health, Aging and Body Composition Study (Health ABC). PARTICIPANTS: Five
      thousand six hundred fifty-four CHS members and 2,706 Health ABC members.
      MEASUREMENTS: Diseases included heart failure (HF), chronic obstructive pulmonary
      disease (COPD), osteoarthritis, and cognitive impairment. The universal health
      outcomes included self-rated health, basic and instrumental activities of daily
      living (ADLs and IADLs), and death. Disease-related symptoms and impairments
      included HF symptoms and ejection fraction (EF) for HF, Dyspnea Scale and forced
      expiratory volume in 1 second for COPD, joint pain for osteoarthritis, and
      executive function for cognitive impairment. RESULTS: The diseases were
      associated with the universal health outcomes (P<.001) except osteoarthritis with
      death (both cohorts) and cognitive impairment with self-rated health (Health
      ABC). Symptoms and impairments accounted for 30% or more of each disease's effect
      on the universal health outcomes. In CHS, for example, HF was associated with one
      fewer (0.918) ADL and IADL performed without difficulty than no HF; HF symptoms
      accounted for 27% of this effect and EF for only 5%. The hazard ratio for death
      with HF was 6.5 (95% confidence interval=4.7-8.9) with EF accounting for 40% and
      HF symptoms for only 14%. CONCLUSION: Disease-related symptoms and impairments
      accounted for much of the significant associations between the four chronic
      diseases and the universal health outcomes. Results support considering universal
      health outcomes as common metrics across diseases in clinical decision-making,
      perhaps by targeting the disease-related symptoms and impairments that contribute
      most strongly to the effect of the disease on the universal health outcomes.

PMID- 21883123
TI  - Postoperative respiratory and analgesic effects of dexmedetomidine or morphine
      for adenotonsillectomy in children with obstructive sleep apnoea.
AB  - The postoperative respiratory and analgesic effects of dexmedetomidine and
      morphine have not been compared in children with sleep apnoea having
      adenotonsillectomy. In a randomised double-blind study we recruited 60 children,
      aged 2-13 years, who received either intravenous dexmedetomidine 1 MUg.kg(-1) or
      morphine 100 MUg.kg(-1) on anaesthetic induction. End-tidal carbon dioxide,
      Children's Hospital of Eastern Ontario Pain Scale score and supplementary
      morphine administration were recorded every 15 min for 60 min postoperatively.
      Over 60 min, mean (SD) end-tidal carbon dioxide was consistently lower with
      dexmedetomidine compared with morphine (5.4 (0.7) kPa vs 6.0 (0.6) kPa,
      respectively; p = 0.001). Mean (SD) pain scores were higher with dexmedetomidine
      (8.1 (2.0) immediately postoperatively and 6.7 (1.0) at 60 min vs 7.6 (1.8) and
      6.3 (0.7), respectively, with morphine (p = 0.023)). More patients required
      supplementary morphine with dexmedetomidine (13/30 (43%) vs 21/30 (70%); p =
      0.037). Postoperatively, dexmedetomidine produced less respiratory depression
      than morphine, but less effective analgesia.

PMID- 21883124
TI  - Low-dose desmopressin improves hypothermia-induced impairment of primary
      haemostasis in healthy volunteers.
AB  - Mild hypothermia (34-35  degrees C) increases peri-operative blood loss. We have
      previously demonstrated the beneficial effect of in vitro desmopressin on
      impairment of primary haemostasis associated with hypothermia. This study
      evaluated subcutaneous desmopressin in 52 healthy volunteers, randomly assigned
      to receive either normal saline or desmopressin 1.5, 5 or 15 MUg (with 13 in each
      group). Blood samples were collected before and 2 h after drug administration and
      incubated at 32 and 37  degrees C. Platelet function analyser PFA-100((r))
      closure times were measured. Hypothermia at 32  degrees C prolonged mean (95% CI)
      closure times (for adenosine diphosphate/collagen by 11.3% (7.5-15.2%) and for
      adrenaline/collagen by 16.2% (11.3-21.2%); these changes were reversed by
      desmopressin. A very small dose was found to be effective (1.5 MUg); this dose
      did not significantly change closure times at 37  degrees C, but fully prevented
      its prolongation at 32  degrees C. Subcutaneous desmopressin prevents the
      development of hypothermia-induced impairment of primary haemostasis.

PMID- 21883125
TI  - A randomised controlled trial of two analgesic techniques for paediatric
      tonsillectomy*.
AB  - Investigators from Bristol described a fentanyl- and diclofenac-based analgesic
      technique for tonsillectomy with low postoperative nausea and vomiting rates and
      low pain scores. This study compared the effectiveness of a modified Bristol
      technique with a codeine-based regimen with respect to PONV and analgesia. Sixty
      five children, ASA 1-2, were randomly assigned to either the Bristol group
      (fentanyl 1-2 MUg.kg(-1) and diclofenac 1-2 mg.kg(-1)) or codeine group (codeine
      1.5 mg.kg(-1)). All children received paracetamol 15 mg.kg(-1) and dexamethasone
      0.1 mg.kg(-1) . Postoperative nausea and vomiting and pain scores were recorded
      hourly, and fitness for discharge was assessed at 4 h. The overall incidence of
      postoperative nausea and vomiting was 21% with no difference between groups
      (Bristol group 8/30, codeine group 5/32, p = 0.29). Children in the Bristol group
      required analgesia earlier than those in the codeine group (p < 0.005), but
      maximum pain scores were not different (Bristol group median (IQR [range) 4.5 (3
      5 [0-5]), codeine group 4.0 (2-5 [1-5]), p = 0.15). Twenty-three per cent of
      children were assessed as not fit for discharge at 4 h. The codeine-based regimen
      may have a small advantage over the Bristol regimen, but neither technique seems
      ideally suited for a day-case service without a longer period of observation. You
      can respond to this article at http://www.anaesthesiacorrespondence.com.

PMID- 21883126
TI  - Communications during epidural catheter placement for labour analgesia.
AB  - Evidence suggests that anaesthetists' communication can affect patient
      experience. There is a lack of guidance for anaesthetists as to the optimal
      verbal communication to use during insertion of epidurals on the labour ward. We
      recorded the verbal communication used by 14 anaesthetists during the siting of
      epidural catheters in women on the labour ward; a classification of the language
      used was subsequently devised. We found that commands and information statements
      were the most common types of communication used. Individual anaesthetists
      differed markedly in their use of positive and negative verbal language. This
      classification of verbal communication that we produced may be of value in future
      training and research of verbal communication used by anaesthetists on the labour
      ward.

PMID- 21883127
TI  - Ability of patients to retain and recall new information in the post-anaesthetic
      recovery period: a prospective clinical study in day surgery.
AB  - Patients are frequently told new information in the early postoperative period
      and may retain little of it. Two hundred patients undergoing general anaesthesia
      for day surgery procedures were randomly allocated into two equal groups, 'Early'
      and 'Late'. Both groups were asked to undertake a simple memory test either in
      the early or late postoperative phase of their recovery. A list of five objects
      was verbally presented and recall of these five objects was tested after 30 min.
      A control group of 100 patients performed the same test. Patients in the control
      group received no sedative medications. Statistically significant differences (p
      < 0.001) in recall ability were demonstrable between each of the three groups.
      Twenty-three percent of patients in the 'Early' group had total amnesia of any
      test information given. Only 1% of the 'Late' group were unable to remember any
      information; a mean interval of 40 min separated the two groups. We recommend
      that verbal information given postoperatively be delayed until a recovery
      interval of at least 40 in, and should be supported with written material.

PMID- 21883128
TI  - A quality assurance programme for cell salvage in cardiac surgery.
AB  - At the same time as cell salvage was introduced into our institution for all
      patients undergoing cardiac surgery with cardiopulmonary bypass, we established a
      supporting programme of quality assurance to reassure clinicians regarding safety
      and efficacy. Data collected in patients operated on between 2001 and 2007
      included pre- and post-wash heparin concentration, haemoglobin concentration and
      free haemoglobin concentration. Cell salvage was used in 6826 out of a total of
      7243 patients (94%). Post-wash heparin concentration was consistently low (always
      < 0.4 IU.ml(-1)). There was a significant decrease in post-wash haemoglobin
      concentration in 2003 compared to 2001, from a median (IQR [range]) of 19.6 (16.7
      22.2 [12.9-25.5]) g.dl(-1) to 17.5 (13.6-20.8 [12.6-23.7]) g.dl(-1) (p < 0.015).
      In addition, there was a significant increase in free plasma haemoglobin in 2006
      compared to 2001, from 0.5 (0.3-0.8 [0.1-2.6]) g.l(-1) to 0.8 (0.3-1.4 [0.3-5.2])
      g.l(-1) (p < 0.001). This programme led to the detection of a change in operator
      behaviour in 2003 and progressive machine deterioration resulting in appropriate
      fleet replacement in 2006. You can respond to this article at
      http://www.anaesthesiacorrespondence.com.

PMID- 21883130
TI  - Airtraq laryngoscope versus conventional Macintosh laryngoscope: a systematic
      review and meta-analysis.
AB  - The Airtraq laryngoscope is a single-use laryngoscope designed to facilitate
      tracheal intubation in patients with either normal or difficult airways. The aim
      of this systematic review and meta-analysis was to compare the Airtraq with the
      conventional Macintosh laryngoscope. Data were retrieved from Medline, Embase,
      the Cochrane register of controlled trials, and by a manual search of
      bibliographies. Twelve randomised controlled trials (published between 2006 and
      2011) including 1061 patients met the inclusion criteria. The Airtraq reduced
      intubation time significantly (mean difference -15 s; 95% CI -25 to -4 s, p <
      0.00001) used by both experienced anaesthetists and novices, and it increased the
      first attempt success rate only in novices (relative risk 1.25; 95% CI 1.05-1.49,
      p = 0.07). The incidence of oesophageal intubation (relative risk 0.12; 95% CI
      0.03-0.48, p < 0.05) was significantly reduced by the Airtraq. We conclude that
      the Airtraq laryngoscope facilitates a more rapid and accurate intubation,
      especially when used by novices.

PMID- 21883131
TI  - Performance of the C-MAC video laryngoscope in patients after a limited glottic
      view using Macintosh laryngoscopy.
AB  - We applied the C-MAC videolaryngoscope in 52 consecutive patients who were found
      to have an unexpected Cormack and Lehane grade-3 (n = 49) and grade-4 (n = 3)
      laryngeal view with the Macintosh laryngoscope. The glottic view improved in 49
      (94%) patients using the C-MAC. Tracheal intubation was successful in 49 of 52
      patients (94%). In one patient, tracheal intubation failed using the C-MAC
      despite the presence of a Cormack and Lehane grade-2. These results suggest that
      the C-MAC videolaryngoscope has a role as a rescue device in cases of an
      initially difficult laryngeal view.

PMID- 21883132
TI  - A cohort evaluation of the paediatric i-gel(TM) airway during anaesthesia in 120
      children.
AB  - We studied the i-gelTM in 120 anaesthetised children (92 boys, 28 girls; median
      (IQR [range]) age (3 -7 [0.4 -13]) years and weight 19 (15-26 [7-35]) kg) to
      assess efficacy and usability. Insertion was successful on the first/second/third
      attempt in 110/8/1 children and failed in one child. Median (IQR [range])
      insertion time was 14 (9-16 [6-200]) s. Manual ventilation was possible in all
      cases, although excess leak precluded a tidal volume above 7 ml.kg(-1) in three
      children. Fibreoptic inspection through the i-gel revealed a clear view of the
      vocal cords in 40 out of 46 cases (87%). Median (IQR [range]) leak pressure was
      20 (16-26 [8-30]) cmH(2) O. During maintenance of anaesthesia, 16 manipulations
      were required in 11 children to improve the airway. One child regurgitated
      without aspirating. Other complications and side effects were infrequent. The i
      gel was inserted without complications, establishing a clear airway and enabling
      spontaneous and controlled ventilation, in 113 (94%) children.

PMID- 21883133
TI  - Using penalised logistic regression to fine map HLA variants for rheumatoid
      arthritis.
AB  - Rheumatoid arthritis (RA) is strongly associated with the human leukocyte antigen
      (HLA) genomic region, most notably with a group of HLA-DRB1 alleles termed the
      shared epitope (SE). There is also substantial evidence of other risk loci in the
      HLA region, but refinement has been hampered by extensive linkage disequilibrium
      (LD). Using genotype imputation, we analysed 6575 RA cases and controls with
      genotypes at 6180 HLA SNPs; about half the subjects had four-digit DRB1
      genotypes. Single-SNP tests revealed hundreds of strong associations across the
      HLA region, even after adjusting for DRB1. We implemented penalised logistic
      regression in a multi-SNP association analysis using the double-exponential (DE)
      penalty term on the regression coefficients and the normal-exponential-gamma
      (NEG). The penalised approaches identified sparse sets of SNPs that could
      collectively explain most of the association with RA over the whole HLA region.
      The HLA-DPB1 SNP rs3117225, was consistently identified in our analyses and was
      confirmed by results from the North American Rheumatoid Arthritis Consortium
      study (NARAC). We conclude that SNP selection using penalised regression shows a
      substantial benefit over single-SNP analyses in identifying risk loci in regions
      of high LD, and the flexibility of the NEG conveys additional advantages.

PMID- 21883134
TI  - Diagnosis and treatment of hypertension 21 years after a hypertensive disorder of
      pregnancy.
AB  - BACKGROUND: Women with a history of hypertensive disorders of pregnancy (HDP) are
      known to be at increased risk of subsequent hypertension and cardiovascular
      disease. AIMS: In this study, we aimed to assess whether the long-term follow-up,
      diagnosis and treatment of hypertension in these women is adequate. METHODS:
      Prospective study of 2112 women who were part of a Birth Cohort Study - The Mater
      University of Queensland Study of Pregnancy, who received antenatal care at a
      major public hospital in Brisbane between 1981 and 1983 and were followed up at
      21 years. RESULTS: Of the 191 women who had HDP, 62 (32.46%) were hypertensive
      (29 adequately treated, 33 inadequately identified or managed). Of the 1921 women
      without HDP, 280 (14.58%) were hypertensive (113 adequately treated, 167
      inadequately identified or managed). Women with HDP were at higher risk of
      hypertension (OR 4.09, 95% CI 2.76, 6.07). Women with a history of HDP were more
      likely to have hypertension that was inadequately identified or managed (OR 3.56,
      95% CI 2.06, 5.97). CONCLUSION: Women with HDP are at increased risk of
      undiagnosed or undertreated hypertension. Attention needs to be given to
      appropriate follow-up of women who have a pregnancy complicated by hypertensive
      disorders.

PMID- 21883135
TI  - Urinary placental growth factor differentiates the hypertensive disorders of
      pregnancy.
AB  - AIMS:   To evaluate the discriminating capacity of urinary placental growth
      factor (uPlGF) for different hypertensive diseases of pregnancy during the third
      trimester. METHODS:   A prospective descriptive case-control study conducted in
      an urban tertiary referral hospital and district general hospital, Sydney South
      West Area Health Service, Australia. Inpatients and outpatients with and without
      hypertension in the third trimester were recruited. Eligible patients provided a
      urine sample for protein, creatinine and a uPlGF level by ELISA. Patients were
      categorised into clinical hypertensive groups based on the diagnostic criteria of
      SOMANZ. RESULTS:   Eighty-eight women were evaluated; 41 had hypertension (15 pre
      eclampsia; 13 gestational hypertension; eight chronic hypertension; five pre
      eclampsia superimposed on chronic hypertension) and 47 women without hypertension
      as the control group. There was a significant difference in uPlGF levels between
      the pre-eclamptic group (median 2.56 IQR 1.12-4.51) and the normotensive controls
      (median 13.18 IQR 5.95-31.39) (P < 0.0001); the gestational hypertensive group
      (median 3.74 IQR 2.49-4.91) and the normotensive group (median 13.18 IQR 5.95
      31.39) (P=0.002) and for a subgroup comparison of placental-mediated hypertension
      (median 2.75 IQR 1.38-4.82) versus non-placental-mediated hypertensives (median
      6.96 IQR 3.87-12.54) (P=0.007). CONCLUSIONS:   Urinary placental growth factor is
      a simple non-invasive test, which is discriminatory for pre-eclampsia in the
      third trimester of pregnancy. Results from this study indicate that it may be
      discriminatory for hypertension related to placental dysfunction (pre-eclampsia
      and gestational hypertension) when compared with hypertension unrelated to
      placental function. Further work is required to assess the ability to detect
      hypertensive diseases before they are clinically apparent.

PMID- 21883136
TI  - Septic shock following cervical cerclage for advanced cervical dilatation.

PMID- 21883139
TI  - Chronic lymphocytic leukaemia responsive to vitamin D administration.

PMID- 21883140
TI  - Genomic analysis of non-splenic marginal zone lymphomas (MZL) indicates
      similarities between nodal and extranodal MZL and supports their derivation from
      memory B-cells.
AB  - Three distinct categories of marginal zone lymphomas (MZLs) are currently
      recognized, principally based on their site of occurrence. They are thought to
      represent unique entities, but the relationship of one subtype with another is
      poorly understood. We investigated 17 non-splenic MZLs (seven nodal, 10
      extranodal) by gene expression profiling to distinguish between subtypes and
      determine their cell of origin. Our findings suggest biological inter-relatedness
      of these entities despite occurrence at different locations and associations with
      possibly different aetiologies. Furthermore, the expression profiles of non
      splenic MZL were similar to memory B cells.

PMID- 21883137
TI  - Lack of evidence for a protective effect of prolonged breastfeeding on childhood
      eczema: lessons from the International Study of Asthma and Allergies in Childhood
      (ISAAC) Phase Two.
AB  - BACKGROUND: Exclusive breastfeeding for at least 4 months is recommended by many
      governments and allergy organizations to prevent allergic disease. OBJECTIVES: To
      investigate whether exclusive breastfeeding protects against childhood eczema.
      METHODS: Study subjects comprised 51,119 randomly selected 8- to 12-year-old
      schoolchildren in 21 countries. Information on eczema and breastfeeding was
      gathered by parental questionnaire. Children were also examined for flexural
      eczema and underwent skin prick testing. Odds ratios (ORs) were calculated for
      each study centre and then pooled across populations. RESULTS: There was a small
      increase in the risk of reported 'eczema ever' in association with 'breastfeeding
      ever' and breastfeeding < 6 months [pooled adjusted OR 1.11, 95% confidence
      interval (CI) 1.00-1.22 and OR 1.10, 95% CI 1.02-1.20, respectively]. There was
      no significant association between reported 'eczema ever' and breastfeeding > 6
      months (pooled adjusted OR 1.09, 95% CI 0.94-1.26). Risk estimates were very
      similar for exclusive breastfeeding < 2 months, 2-4 months and > 4 months and for
      eczema symptoms in the past 12 months and eczema on skin examination. As for more
      severe eczema, breastfeeding per se conveyed a risk reduction on sleep disturbed
      eczema (pooled adjusted OR 0.71, 95% CI 0.53-0.96), but this effect was lost
      where children had been exclusively breastfed for > 4 months (pooled adjusted OR
      1.02, 95% CI 0.67-1.54). Allergic sensitization and a history of maternal
      allergic disease did not modify any of these findings. CONCLUSIONS: Although
      there was a protective effect of ever having been breastfed on more severe
      disease, we found no evidence that exclusive breastfeeding for 4 months or longer
      protects against eczema. Our results are consistent with findings from a recent
      systematic review of prospective studies. The U.K. breastfeeding guidelines with
      regard to eczema should be reviewed. Intervention studies are now required to
      explore how and when solids should be introduced alongside breastfeeding to aid
      protection against eczema and other allergic diseases.

PMID- 21883141
TI  - Combination chemotherapy with clofarabine, cyclophosphamide, and etoposide in
      children with refractory or relapsed haematological malignancies.

PMID- 21883144
TI  - Activation of transient receptor potential A1 by a non-pungent capsaicin-like
      compound, capsiate.
AB  - BACKGROUND AND PURPOSE: Capsiate is produced by 'CH-19 Sweet' (Capsicum annuun
      L.), a non-pungent cultivar of red pepper. Like capsaicin, capsiate is thought to
      enhance energy metabolism by activating the sympathetic nervous system and
      suppressing inflammation, but the underlying mechanisms for this are uncertain.
      We previously reported that capsiate could activate transient receptor potential
      vanilloid 1 (TRPV1), a capsaicin receptor. The purpose of the present study is to
      investigate whether capsinoids activate other TRP channels. EXPERIMENTAL
      APPROACH: Using Ca(2+) imaging and whole-cell patch-clamp methods, we analysed
      the response of TRP channels to three kinds of capsinoids, capsiate,
      dihydrocapsiate and nordihydrocapsiate, in HEK293T cells expressing TRP channels
      or in primary cultures of mouse dorsal root ganglion neurons. KEY RESULTS: We
      found that in both cell types TRP ankyrin 1 (TRPA1) had a slightly weaker
      response to capsinoids compared with TRPV1, with the capsiate EC(50) for TRPA1
      activation being more than that for TRPV1 activation, and that the capsinoid
      evoked action was blocked by a specific TRPA1 antagonist. TRPA1 was activated by
      capsinoids, but not by their degradation products. Amino acids known to
      participate in TRPA1 activation following cysteine covalent modification or zinc
      treatment were not involved in the activation of TRPA1 by capsinoid. CONCLUSIONS
      AND IMPLICATIONS: Taken together, these results indicate that capsinoids activate
      TRPA1 by an as yet unknown mechanism, and TRPA1 could be involved in
      physiological phenomena associated with capsinoid treatment.

PMID- 21883143
TI  - Insights into mechanisms of corticotropin-releasing hormone receptor signal
      transduction.
AB  - During evolution, mammals have developed remarkably similar molecular mechanisms
      to respond to external challenges and maintain survival. Critical regulators of
      these mechanisms are the family of 'stress'-peptides that consists of the
      corticotropin-releasing hormone (CRH) and urocortins (Ucns). These neuropeptides
      'fine-tune' integration of an intricate series of physiological responses
      involving the autonomic, endocrine, immune, cardiovascular and reproductive
      systems, which induce a spectrum of behavioural and homeostatic changes. CRH and
      Ucns exert their actions by activating two types of CRH receptors (CRH-R), CRH-R1
      and CRH-R2, which belong to the class-B1 family of GPCRs. The CRH-Rs exhibit
      signalling promiscuity facilitated by their ability to couple to multiple G
      proteins and regulate diverse intracellular networks that involve intracellular
      effectors such as cAMP and an array of PKs in an agonist and tissue-specific
      manner, a property that allows them to exert unique roles in the integration of
      homeostatic mechanisms. We only now begin to unravel the plethora of CRH-R
      biological actions and the transcriptional and post-translational mechanisms such
      as alternative mRNA splicing or phosphorylation-mediated desensitization
      developed to tightly control CRH-Rs biological activity and regulate their
      physiological actions. This review summarizes the current understanding of CRH-R
      signalling complexity and regulatory mechanisms that underpin cellular responses
      to CRH and Ucns.

PMID- 21883145
TI  - Ketamine-induced ventricular structural, sympathetic and electrophysiological
      remodelling: pathological consequences and protective effects of metoprolol.
AB  - BACKGROUND AND PURPOSE: Growing evidence suggests that long-term abuse of
      ketamine does harm the heart and increases the risk of sudden death. The present
      study was performed to explore the cardiotoxicity of ketamine and the protective
      effects of metoprolol. EXPERIMENTAL APPROACH: Rats and rabbits were divided into
      control, ketamine, metoprolol alone and ketamine plus metoprolol groups. Ketamine
      (40 mg.kg(-1) .day(-1), i.p.) and metoprolol (20 mg.kg(-1) .day(-1), p.o.) were
      administered continuously for 12 weeks in rats and 8 weeks in rabbits. Cardiac
      function, electrophysiological disturbances, cardiac collagen, cardiomyocte
      apoptosis and the remodelling-related proteins were evaluated. KEY RESULTS:
      Rabbits treated with ketamine showed decreased left ventricular ejection
      fraction, slowed ventricular conduction velocity and increased susceptibility to
      ventricular arrhythmia. Metoprolol prevented these pathophysiological
      alterations. In ketamine-treated rats, cardiac collagen volume fraction and
      apoptotic cell number were higher than those of control animals; these effects
      were prevented by co-administration of metoprolol. Consistently, the expressions
      of poly (ADP-ribose) polymerases-1, apoptosis-inducing factor and NF-kappaB-light
      chain-enhancer of activated B cells were all increased after ketamine treatment
      and sharply reduced after metoprolol administration. Moreover, ketamine enhanced
      sympathetic sprouting, manifested as increased growth-associated protein 43 and
      tyrosine TH expression. These effects of ketamine were prevented by metoprolol.
      CONCLUSIONS AND IMPLICATIONS: Chronic treatment with ketamine caused significant
      ventricular myocardial apoptosis, fibrosis and sympathetic sprouting, which
      altered the electrophysiological properties of the heart and increased its
      susceptibility to malignant arrhythmia that may lead to sudden cardiac death.
      Metoprolol prevented the cardiotoxicity of ketamine, indicating a promising new
      therapeutic strategy.

PMID- 21883142
TI  - Evolving insights in the pathogenesis and therapy of cutaneous T-cell lymphoma
      (mycosis fungoides and Sezary syndrome).
AB  - Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of malignancies
      derived from skin-homing T cells. The most common forms of CTCL are Mycosis
      Fungoides (MF) and Sezary Syndrome (SS). Accurate diagnosis remains a challenge
      due to the heterogeneity of presentation and the lack of highly characteristic
      immunophenotypical and genetic markers. Over the past decade molecular studies
      have improved our understanding of the biology of CTCL. The identification of
      gene expression differences between normal and malignant T-cells has led to
      promising new diagnostic and prognostic biomarkers that now need validation to be
      incorporated into clinical practice. These biomarkers may also provide insight
      into the mechanism of development of CTCL. Additionally, treatment options have
      expanded with the approval of new agents, such as histone deacetylase inhibitors.
      A better understanding of the cell biology, immunology and genetics underlying
      the development and progression of CTCL will allow the design of more rational
      treatment strategies for these malignancies. This review summarizes the clinical
      epidemiology, staging and natural history of MF and SS; discusses the
      immunopathogenesis of MF and the functional role of the malignant T-cells; and
      reviews the latest advances in MF and SS treatment.

PMID- 21883146
TI  - Slow receptor dissociation is not a key factor in the duration of action of
      inhaled long-acting beta2-adrenoceptor agonists.
AB  - BACKGROUND AND PURPOSE: beta(2) -Adrenoceptor agonists are important
      bronchodilators used for the treatment of chronic obstructive pulmonary disease
      and asthma. Clinical data on beta(2) -adrenoceptor agonists show a range of onset
      and duration of action. We have investigated whether the receptor binding
      kinetics of beta(2) -adrenoceptor agonists can explain their observed onset of
      action and duration of effect in the clinic. EXPERIMENTAL APPROACH: [(3) H]-DHA
      was used to label beta(2) -adrenoceptors expressed in CHO-cell membranes (K(d) of
      0.084 nM). Competition kinetic experiments were performed in the presence of
      unlabelled beta(2) agonists at 37 degrees C in HBSS containing GTP. To determine
      the kinetic parameters, three concentrations (10, 3 and 1 *K(i) ) of the
      unlabelled compound were employed against a fixed concentration of [(3) H]-DHA
      (0.6 nM). KEY RESULTS: The clinically used beta(2) -adrenoceptor agonists
      exhibited a range of association and dissociation rates. The kinetic K(d) and the
      competition K(i) values of the eight beta(2) -adrenoceptor agonists examined were
      strongly correlated, suggesting that the method had produced accurate k(off) and
      k(on) rates. The kinetic on-rate was highly correlated with equilibrium binding
      affinity. CONCLUSIONS AND IMPLICATIONS: Although the beta(2) -adrenoceptor
      agonists displayed a range of kinetic rate parameters, simulations at relevant
      drug concentrations suggest that receptor kinetics do not play an important role
      in determining onset of action in the clinic. In addition, it is unlikely that
      receptor kinetics exert an important influence on the duration of action of these
      agonists, as indacaterol (once daily dosing) had a shorter residency time at the
      receptor than salmeterol (twice daily dosing).

PMID- 21883147
TI  - Inhibiting fatty acid amide hydrolase normalizes endotoxin-induced enhanced
      gastrointestinal motility in mice.
AB  - BACKGROUND AND PURPOSE: Gastrointestinal (GI) motility is regulated in part by
      fatty acid ethanolamides (FAEs), including the endocannabinoid (EC) anandamide
      (AEA). The actions of FAEs are terminated by fatty acid amide hydrolase (FAAH).
      We investigated the actions of the novel FAAH inhibitor AM3506 on normal and
      enhanced GI motility. EXPERIMENTAL APPROACH: We examined the effect of AM3506 on
      electrically-evoked contractility in vitro and GI transit and colonic faecal
      output in vivo, in normal and FAAH-deficient mice treated with saline or LPS (100
      ug.kg(-1), i.p.), in the presence and absence of cannabinoid (CB) receptor
      antagonists. mRNA expression was measured by quantitative real time-PCR, EC
      levels by liquid chromatography-MS and FAAH activity by the conversion of [(3)H]
      AEA to [(3)H]-ethanolamine in intestinal extracts. FAAH expression was examined
      by immunohistochemistry. KEY RESULTS: FAAH was dominantly expressed in the
      enteric nervous system; its mRNA levels were higher in the ileum than the colon.
      LPS enhanced ileal contractility in the absence of overt inflammation. AM3506
      reversed the enhanced electrically-evoked contractions of the ileum through CB(1)
      and CB(2) receptors. LPS increased the rate of upper GI transit and faecal
      output. AM3506 normalized the enhanced GI transit through CB(1) and CB(2)
      receptors and faecal output through CB(1) receptors. LPS did not increase GI
      transit in FAAH-deficient mice. CONCLUSIONS AND IMPLICATIONS: Inhibiting FAAH
      normalizes various parameters of GI dysmotility in intestinal pathophysiology.
      Inhibition of FAAH represents a new approach to the treatment of disordered
      intestinal motility.

PMID- 21883148
TI  - Structure-activity relationships of vanilloid receptor agonists for arteriolar
      TRPV1.
AB  - BACKGROUND AND PURPOSE: The transient receptor potential vanilloid 1 (TRPV1)
      plays a role in the activation of sensory neurons by various painful stimuli and
      is a therapeutic target. However, functional TRPV1 that affect microvascular
      diameter are also expressed in peripheral arteries and we attempted to
      characterize this receptor. EXPERIMENTAL APPROACH: Sensory TRPV1 activation was
      measured in rats by use of an eye wiping assay. Arteriolar TRPV1-mediated smooth
      muscle specific responses (arteriolar diameter, changes in intracellular Ca(2+))
      were determined in isolated, pressurized skeletal muscle arterioles obtained from
      the rat and wild-type or TRPV1(-/-) mice and in canine isolated smooth muscle
      cells. The vascular pharmacology of the TRPV1 agonists (potency, efficacy,
      kinetics of action and receptor desensitization) was determined in rat isolated
      skeletal muscle arteries. KEY RESULTS: Capsaicin evoked a constrictor response in
      isolated arteries similar to that mediated by noradrenaline, this was absent in
      arteries from TRPV1 knockout mice and competitively inhibited by TRPV1 antagonist
      AMG9810. Capsaicin increased intracellular Ca(2+) in the arteriolar wall and in
      isolated smooth muscle cells. The TRPV1 agonists evoked similar vascular
      constrictions (MSK-195 and JYL-79) or were without effect (resiniferatoxin and
      JYL-273), although all increased the number of responses (sensory activation) in
      the eye wiping assay. Maximal doses of all agonists induced complete
      desensitization (tachyphylaxis) of arteriolar TRPV1 (with the exception of
      capsaicin). Responses to the partial agonist JYL-1511 suggested 10% TRPV1
      activation is sufficient to evoke vascular tachyphylaxis without sensory
      activation. CONCLUSIONS AND IMPLICATIONS: Arteriolar TRPV1 have different
      pharmacological properties from those located on sensory neurons in the rat.

PMID- 21883149
TI  - A beta-amyloid oligomer directly modulates P/Q-type calcium currents in Xenopus
      oocytes.
AB  - BACKGROUND AND PURPOSE: beta-amyloid (Abeta) oligomers have been implicated in
      the early pathophysiology of Alzheimer's disease (AD). While the precise nature
      of the molecular target has not been fully revealed, a number of studies have
      indicated that Abeta oligomers modulate neuron-specific ion channels. We recently
      provided evidence that Abeta oligomers suppress isolated P/Q-type calcium
      currents in cultured nerve cells. Using a heterologous expression system, we
      aimed to prove a direct effect on the membrane channel mediating such current.
      EXPERIMENTAL APPROACH: The effects of a synthetically generated Abeta oligomer,
      Abeta globulomer, were investigated on P/Q-type currents recorded from Xenopus
      laevis oocytes expressing the full P/Q-type calcium channel or the pore-forming
      subunit only. We also examined the effects of Abeta globulomer on recombinant
      NMDA receptor currents. Finally, we compared the modulation by Abeta globulomer
      with that induced by a synthetic monomeric Abeta. KEY RESULTS: Abeta globulomer
      directly and dose-dependently modulated P/Q-type calcium channels. A leftward
      shift of the current-voltage curve indicated that the threshold for channel
      opening was reduced. The effect of Abeta globulomer was also present when only
      the alpha1A subunit of the normally tripartite channel was expressed. In
      contrast, the monomeric Abeta had no effect on P/Q current. Also globulomer Abeta
      had no effect on glutamate-induced NMDA currents. CONCLUSIONS AND IMPLICATIONS:
      The alpha1A subunit of the P/Q-type calcium channel is directly modulated by
      oligomeric Abeta. Threshold reduction as well as an increase in current at
      synaptic terminals may facilitate vesicle release and could trigger excitotoxic
      events in the brains of patients with AD.

PMID- 21883150
TI  - beta(2)-Adrenoceptors increase translocation of GLUT4 via GPCR kinase sites in
      the receptor C-terminal tail.
AB  - BACKGROUND AND PURPOSE: beta-Adrenoceptor stimulation induces glucose uptake in
      several insulin-sensitive tissues by poorly understood mechanisms. EXPERIMENTAL
      APPROACH: We used a model system in CHO-K1 cells expressing the human beta(2)
      adrenoceptor and glucose transporter 4 (GLUT4) to investigate the signalling
      mechanisms involved. KEY RESULTS: In CHO-K1 cells, there was no response to beta
      adrenoceptor agonists. The introduction of beta(2)-adrenoceptors and GLUT4 into
      these cells caused increased glucose uptake in response to beta-adrenoceptor
      agonists. GLUT4 translocation occurred in response to insulin and beta(2)
      adrenoceptor stimulation, although the key insulin signalling intermediate PKB
      was not phosphorylated in response to beta(2)-adrenoceptor stimulation.
      Truncation of the C-terminus of the beta(2)-adrenoceptor at position 349 to
      remove known phosphorylation sites for GPCR kinases (GRKs) or at position 344 to
      remove an additional PKA site together with the GRK phosphorylation sites did not
      significantly affect cAMP accumulation but decreased beta(2)-adrenoceptor
      stimulated glucose uptake. Furthermore, inhibition of GRK by transfection of the
      betaARKct construct inhibited beta(2)-adrenoceptor-mediated glucose uptake and
      GLUT4 translocation, and overexpression of a kinase-dead GRK2 mutant (GRK2 K220R)
      also inhibited GLUT4 translocation. Introducing beta(2)-adrenoceptors lacking
      phosphorylation sites for GRK or PKA demonstrated that the GRK sites, but not the
      PKA sites, were necessary for GLUT4 translocation. CONCLUSIONS AND IMPLICATIONS:
      Glucose uptake in response to activation of beta(2)-adrenoceptors involves
      translocation of GLUT4 in this model system. The mechanism is dependent on the C
      terminus of the beta(2)-adrenoceptor, requires GRK phosphorylation sites, and
      involves a signalling pathway distinct from that stimulated by insulin.

PMID- 21883151
TI  - Pharmacological characterization of a small-molecule agonist for the chemokine
      receptor CXCR3.
AB  - BACKGROUND AND PURPOSE: The chemokine receptor CXCR3 is a GPCR found
      predominantly on activated T cells. CXCR3 is activated by three endogenous
      peptides; CXCL9, CXCL10 and CXCL11. Recently, a small-molecule agonist, VUF10661,
      has been reported in the literature and synthesized in our laboratory. The aim of
      the present study was to provide a detailed pharmacological characterization of
      VUF10661 by comparing its effects with those of CXCL11. EXPERIMENTAL APPROACH:
      Agonistic properties of VUF10661 were assessed in a chemotaxis assay with murine
      L1.2 cells transiently transfected with cDNA encoding the human CXCR3 receptor
      and in binding studies, with [(125)I]-CXCL10 and [(125)I]-CXCL11, on membrane
      preparations from HEK293 cells stably expressing CXCR3. [(35)S]-GTPgammaS binding
      was used to determine its potency to induce CXCR3-mediated G protein activation
      and BRET-based assays to investigate its effects on intracellular cAMP levels and
      beta-arrestin recruitment. KEY RESULTS: VUF10661 acted as a partial agonist in
      CXCR3-mediated chemotaxis, bound to CXCR3 in an allosteric fashion in ligand
      binding assays and activated G(i) proteins with the same efficacy as CXCL11 in
      the [(35)S]-GTPgammaS binding and cAMP assay, while it recruited more beta
      arrestin1 and beta-arrestin2 to CXCR3 receptors than the chemokine. CONCLUSIONS
      AND IMPLICATIONS: VUF10661, like CXCL11, activates both G protein-dependent and 
      independent signalling via the CXCR3 receptor, but probably exerts its effects
      from an allosteric binding site that is different from that for CXCL11. It could
      stabilize different receptor and/or beta-arrestin conformations leading to
      differences in functional output. Such ligand-biased signalling might offer
      interesting options for the therapeutic use of CXCR3 agonists.

PMID- 21883152
TI  - Ethnic stigma, academic anxiety, and intrinsic motivation in middle childhood.
AB  - Previous research addressing the dynamics of stigma and academics has focused on
      African American adolescents and adults. The present study examined stigma
      awareness, academic anxiety, and intrinsic motivation among 451 young (ages 6-11)
      and diverse (African American, Chinese, Dominican, Russian, and European
      American) students. Results indicated that ethnic-minority children reported
      higher stigma awareness than European American children. For all children, stigma
      awareness was associated with higher academic anxiety and lower intrinsic
      motivation. Despite these associations, ethnic-minority children reported higher
      levels of intrinsic motivation than their European American peers. A significant
      portion of the higher intrinsic motivation among Dominican students was
      associated with their higher levels of school belonging, suggesting that
      supportive school environments may be important sources of intrinsic motivation
      among some ethnic-minority children.

PMID- 21883153
TI  - Antecedents and outcomes of joint trajectories of mother-son conflict and warmth
      during middle childhood and adolescence.
AB  - This study investigated the development of mother-son relationship quality from
      ages 5 to 15 in a sample of 265 low-income families. Nonparametric random effects
      modeling was utilized to uncover distinct and homogeneous developmental
      trajectories of conflict and warmth; antecedents and outcomes of the trajectory
      groups also were examined. Four conflict trajectory groups and 3 warmth
      trajectory groups were identified. Difficult temperament in early childhood
      discriminated both conflict and warmth trajectory group membership (TGM), and
      adult relationship quality in early childhood was related to warmth trajectories.
      In addition, conflict TGM differentiated youth antisocial behavior during
      adolescence, and warmth trajectories predicted adolescent peer relationship
      quality and youth moral disengagement. Implications for socialization processes
      are discussed.

PMID- 21883154
TI  - Developing relationships, being cool, and not looking like a loser: social goal
      orientation predicts children's responses to peer aggression.
AB  - This research explored the contribution of social goal orientation, specifically,
      development (improving social skills and relationships), demonstration-approach
      (gaining positive judgments), and demonstration-avoidance (minimizing negative
      judgments). Children (N = 373; M age = 7.97, SD = .34) were followed from 2nd to
      3rd grades. Validity of the social goal orientation construct was established
      through correlations with situation-specific goals and social adjustment.
      Development goals predicted adaptive responses (more effortful engagement,
      problem solving, advice seeking; fewer involuntary responses); demonstration
      goals predicted maladaptive responses (less effortful engagement, problem
      solving; more disengagement, retaliation). This study contributes to theoretical
      understanding of the process of peer aggression and interventions to promote
      optimal social health.

PMID- 21883155
TI  - Characterizing and comparing the friendships of anxious-solitary and unsociable
      preadolescents.
AB  - Friendships matter for withdrawn youth because the consequences of peer isolation
      are severe. From a normative sample of 2,437 fifth graders (1,245 females; M age
      = 10.25), a subset (n = 1,364; 638 female) was classified into 3 groups (anxious
      solitary, unsociable, comparison) and followed across a school year. Findings
      indicated that it was more common for unsociable than anxious-solitary children
      to have friends, be stably friended, and participate in multiple friendships. For
      withdrawn as well as nonwithdrawn children, peer rejection predicted
      friendlessness, but this relation was strongest for anxious-solitary children.
      The friends of unsociable youth were more accepted by peers than those of anxious
      solitary youth. The premise that friendship inhibits peer victimization was
      substantiated for withdrawn as well as nonwithdrawn youth.

PMID- 21883156
TI  - Developmental continuity in theory of mind: speed and accuracy of belief-desire
      reasoning in children and adults.
AB  - On belief-desire reasoning tasks, children first pass tasks involving true belief
      before those involving false belief, and tasks involving positive desire before
      those involving negative desire. The current study examined belief-desire
      reasoning in participants old enough to pass all such tasks. Eighty-three 6- to
      11-year-olds and 20 adult participants completed simple, computer-based tests of
      belief-desire reasoning, which recorded response times as well as error rates.
      Both measures suggested that, like young children, older children and adults find
      it more difficult to reason about false belief and negative desires than true
      beliefs and positive desires. It is argued that this developmental continuity is
      most consistent with either executive competence or executive performance
      accounts of the development of belief-desire reasoning.

PMID- 21883158
TI  - Social groups and children's intergroup attitudes: can school norms moderate the
      effects of social group norms?
AB  - The effects of social group norms (inclusion vs. exclusion vs. exclusion-plus
      relational aggression) and school norms (inclusion vs. no norm) on 7- and 10-year
      old children's intergroup attitudes were examined. Children (n = 383) were
      randomly assigned to a group with an inclusion or exclusion norm, and to 1 of the
      school norm conditions. Findings indicated that children's out-group attitudes
      reflected their group's norm but, with increasing age, they liked their in-group
      less, and the out-group more, if the group had an exclusion norm. The school
      inclusion norm instigated more positive attitudes toward out-group members, but
      it did not moderate or extinguish contrary group norms. The use of school norms
      to counteract the effects of children's social group norms is discussed.

PMID- 21883157
TI  - The effect of narrative cues on infants' imitation from television and picture
      books.
AB  - Infants can imitate a novel action sequence from television and picture books,
      yet there has been no direct comparison of infants' imitation from the 2 types of
      media. Varying the narrative cues available during the demonstration and test,
      the current experiments measured 18- and 24-month-olds' imitation from television
      and picture books. Infants imitated from both media types when full narrative
      cues (Experiment 1; N = 76) or empty, meaningless narration (Experiment 2; N =
      135) accompanied the demonstrations, but they imitated more from television than
      books. In Experiment 3 (N = 27), infants imitated from a book based on narration
      alone, without the presence of pictures. These results are discussed in relation
      to age-related changes in cognitive flexibility and infants' emerging symbolic
      understanding.

PMID- 21883159
TI  - Newborn irritability moderates the association between infant attachment security
      and toddler exploration and sociability.
AB  - This longitudinal investigation of 84 infants examined whether the effect of 12
      month attachment on 18- and 24-month exploration and sociability with unfamiliar
      adults varied as a function of newborn irritability. As expected, results
      revealed an interaction between attachment (secure vs. insecure) and irritability
      (highly irritable vs. moderately irritable) in predicting both exploration and
      sociability with unfamiliar adults. For exploration, results supported a dual
      risk model; that is, toddlers who had been both highly irritable and insecurely
      attached were less exploratory than other toddlers. For sociability, results
      supported the differential-susceptibility hypothesis; that is, highly irritable
      infants, compared to moderately irritable infants, were both less sociable as
      toddlers when they had been insecurely attached and more sociable when they had
      been securely attached.

PMID- 21883160
TI  - Trajectories of parenting and child negative emotionality during infancy and
      toddlerhood: a longitudinal analysis.
AB  - The current longitudinal study examined trajectories of child negative
      emotionality, parenting efficacy, and overreactive parenting among 382 adoptive
      families during infancy and toddlerhood. Data were collected from adoptive
      parents when the children were 9-, 18-, and 27-month-old. Latent growth curve
      modeling indicated age-related increases in child negative emotionality and
      overreactive parenting for adoptive fathers and adoptive mothers (AM), and
      decreases in parent efficacy among AM. Increases in child negative emotionality
      were also associated with increases in parent overreactivity and decreases in
      maternal efficacy. Mothers' and fathers' developmental patterns were linked
      within but not across parenting domains. Limitations and directions for future
      research are discussed.

PMID- 21883163
TI  - Developmental changes in item and source memory: evidence from an ERP recognition
      memory study with children, adolescents, and adults.
AB  - Event-related potential (ERP) correlates of item and source memory were assessed
      in 18 children (7-8 years), 20 adolescents (13-14 years), and 20 adults (20-29
      years) performing a continuous recognition memory task with object and nonobject
      stimuli. Memory performance increased with age and was particularly low for
      source memory in children. The ERP difference between first presentations of
      objects and nonobjects, reflecting generic novelty processing, showed only small
      developmental changes. Regarding item memory, adults showed the putative ERP
      correlates of familiarity and recollection, whereas ERP effects in children and
      adolescents suggested a strong reliance on recollection. ERP correlates of source
      memory refined with age, suggesting maturation of strategic recollection between
      childhood and adolescence and the development of postretrieval control until
      adulthood.

PMID- 21883161
TI  - Differential susceptibility to adolescent externalizing trajectories: examining
      the interplay between CHRM2 and peer group antisocial behavior.
AB  - The present study characterized prototypical patterns of development in self
      reported externalizing behavior, between 12 and 22 years of age, within a
      community sample of 452 genotyped individuals. A Caucasian subset (n = 378) was
      then examined to determine whether their probabilities of displaying discrete
      trajectories were differentially associated with CHRM2, a gene implicated in self
      regulatory processes across a range of externalizing behaviors, and if
      affiliating with antisocial peers moderated these associations. Findings indicate
      that relative to a normative "lower risk" externalizing trajectory, likelihood of
      membership in two "higher risk" trajectories increased with each additional copy
      of the minor allelic variant at CHRM2, and that this association was exacerbated
      among those exposed to higher levels of peer group antisocial behavior.

PMID- 21883164
TI  - The accuracy of risks for cancer in Lynch syndrome.

PMID- 21883162
TI  - Epigenetic vestiges of early developmental adversity: childhood stress exposure
      and DNA methylation in adolescence.
AB  - Fifteen-year-old adolescents (N = 109) in a longitudinal study of child
      development were recruited to examine differences in DNA methylation in relation
      to parent reports of adversity during the adolescents' infancy and preschool
      periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide
      sites within DNA derived from buccal epithelial cells showed differential
      methylation among adolescents whose parents reported high levels of stress during
      their children's early lives. Maternal stressors in infancy and paternal
      stressors in the preschool years were most strongly predictive of differential
      methylation, and the patterning of such epigenetic marks varied by children's
      gender. To the authors' knowledge, this is the first report of prospective
      associations between adversities in early childhood and the epigenetic
      conformation of adolescents' genomic DNA.

PMID- 21883165
TI  - Looping the link between Gaucher and Parkinson's disease.

PMID- 21883166
TI  - Skipping along: an exon skipping therapy shows promise for Duchenne muscular
      dystrophy.

PMID- 21883168
TI  - Analysis of phenotype and genotype information for the diagnosis of Marfan
      syndrome.
AB  - Marfan syndrome is considered a clinical diagnosis. Three diagnostic
      classifications comprising first, Marfan genotype with a causative FBN1 gene
      mutation; second, Marfan phenotype with clinical criteria of the original Ghent
      nosology (Ghent-1); and third, phenotype with clinical criteria of its current
      revision (Ghent-2) in 300 consecutive persons referred for confirmation or
      exclusion of Marfan syndrome (150 men, 150 women aged 35 +/- 13 years) were used.
      Sequencing of TGBR1/2 genes was performed in 128 persons without FBN1 mutation.
      Marfan genotype was present in 140, Ghent-1 phenotype in 139, and Ghent-2
      phenotype in 124 of 300 study patients. Marfan syndrome was confirmed in 94 and
      excluded in 129 persons consistently by all classifications, but classifications
      were discordant in 77 persons. With combined genotype and phenotype information
      confirmation of Marfan syndrome was finally achieved in 126 persons by Ghent-1
      and in 125 persons by Ghent-2 among 140 persons with Marfan genotype, and
      exclusion was accomplished in 139 persons by Ghent-1 and in 141 persons by Ghent
      2 among 160 persons without Marfan genotype. In total, genotype information
      changed final diagnoses in 22 persons with Ghent-1, and in 32 persons with Ghent
      2. It is concluded that genotype information is essential for diagnosis or
      exclusion of Marfan syndrome.

PMID- 21883167
TI  - Development and validation of an instrument to measure the impact of genetic
      testing on self-concept in Lynch syndrome.
AB  - A positive genetic test result may impact on a person's self-concept and affect
      quality of life. The purpose of the study was to develop a self-concept scale to
      measure such impact for individuals carrying mutations for a heritable colorectal
      cancer Lynch syndrome (LS). Two distinct phases were involved: Phase 1 generated
      specific colorectal self-concept candidate scale items from interviews with eight
      LS carriers and five genetic counselors, which were added to a previously
      developed self-concept scale for BRCA1/2 mutation carriers, Phase II had 115 LS
      carriers complete the candidate scale and a battery of validating measures. A 20
      item scale was developed with two dimensions identified through factor analysis:
      stigma/vulnerability and bowel symptom-related anxiety. The scale showed
      excellent reliability (Cronbach's alpha = 0.93), good convergent validity by a
      high correlation with impact of event scale (r(102) = 0.55, p < 0.001) and
      Rosenberg self-esteem scale (r(108) = -0.59, p < 0.001), and a low correlation
      with the Fear questionnaire (r(108) = 0.37, p < 0.001). The scale's performance
      was stable across participant characteristics. This new scale for measuring self
      concept has potential to be used as a clinical tool and as a measure for future
      studies.

PMID- 21883169
TI  - Identification of a yolk sac cell population with hematopoietic activity in view
      of CD45/c-Kit expression.
AB  - During murine embryonic development, primitive hematopoiesis occurs in the yolk
      sac (YS). Recent studies have shown that the YS also harbors definitive
      hematopoietic activity. However, the population of YS cells contributing to
      definitive hematopoiesis has not been identified. In this study, we characterized
      the hematopoietic cell populations in the YS of mouse embryos from E9.5 to E14.5
      in view of the expression profiles of CD45 and c-Kit. The YS cells from E9.5 to
      E11.5 could be divided into six populations: CD45(-) c-Kit(-) , CD45(-) c
      Kit(low) , CD45(-) c-Kit(high) , CD45(low) c-Kit(high) , CD45(high) c-Kit(high)
      and CD45(high) c-Kit(very low) . Among these populations, CD45(low) c-Kit(high)
      cells showed the highest multilineage hematopoietic colony-forming activity.
      Later in development, the YS cells from E12.5 to E14.5 lost the second and fourth
      populations (i.e., they retained CD45(-) c-Kit(-) , CD45(-) c-Kit(high) ,
      CD45(high) c-Kit(high) and CD45(high) c-Kit(very low) cells), and concurrently
      with the disappearance of the CD45(low) c-Kit(high) population, no significant
      hematopoietic activity was found in any of the populations on and after E12.5.
      CD45(low) c-Kit(high) YS cells, which had a round morphology with a large
      nucleus, possessed the ability to differentiate into myeloid and B lymphoid cells
      when cultured with stromal cells. These findings suggest that CD45(low) c
      Kit(high) YS cells include more undifferentiated cells than the other YS cell
      populations and possess in vitro potency to differentiate into multilineage
      hematopoietic cells. Furthermore, this cell population disappears from the YS at
      around E12.5, when the site of hematopoiesis has already shifted to the fetal
      liver and the placenta.

PMID- 21883170
TI  - Wearable wrist activity monitor as an indicator of functional hand use in
      children with cerebral palsy.
AB  - AIM: New tools that capture hand function in everyday activities and contexts are
      needed for assessing children with hemiplegic cerebral palsy. This study
      evaluates a wearable wrist monitor and tests the hypothesis that wrist extension
      frequency (FreqE) is an appropriate indicator of functional hand use. METHOD:
      Fifteen children (four females, 11 males; age range 6-12y; mean age 10y [SD 2y])
      with hemiplegia (seven at level I and eight at level II on the Manual Ability
      Classification System) participated in the Assisting Hand Assessment (AHA) while
      wearing the wrist monitor. FreqEs were captured via the wrist monitor and
      validated using video analysis. Correlations between FreqE and AHA scores were
      calculated and a multivariate linear regression was conducted to explore other
      measures of wrist activity. RESULTS: Wrist extensions observed in video analyses
      were reliably detected by the wrist monitor (intraclass correlation coefficient,
      r=0.88; p<0.001) and were strongly correlated with the AHA scores (r=0.93;
      p<0.001). AHA scores were significantly correlated with FreqE (r=0.80; p=0.001)
      and the range of wrist extensions/flexions (r=0.70; p=0.008). The multivariate
      linear regression combining the FreqE and range of wrist extensions/flexions
      yielded a strong correlation with AHA scores (r=0.84; p=0.0043). INTERPRETATION:
      The wearable wrist monitor may offer a convenient, valid alternative to observer
      reports for functional assessments of the hemiplegic hand in everyday contexts.

PMID- 21883171
TI  - Postural adaptations to a suprapostural memory task among children with and
      without developmental coordination disorder.
AB  - AIM: The present study investigated the effects of varying the cognitive demands
      of a memory task (a suprapostural task) while recording postural motion on two
      groups of children, one diagnosed with developmental coordination disorder (DCD)
      and an age-matched group of typically developing children. METHOD: Two groups,
      each comprising 38 child volunteers (21 males, 17 females) aged 9 to 10 years,
      participated in the study. Each child performed a digital memory task at two
      levels of difficulty, low and high. Positional variability (standard deviation of
      position) of the head and torso were recorded as the biomechanical responses to
      the variation in task difficulty. RESULTS: Both groups significantly reduced
      postural motion when engaged in the high-difficulty condition (p<0.05) compared
      with the low-difficulty condition. Children with DCD exhibited significantly
      higher levels of postural motion (p<0.05) than the typically developing children.
      The typically developing children significantly reduced their postural motion in
      the high-difficulty condition (p<0.05) compared with the low-difficulty
      condition, whereas children with DCD did not. INTERPRETATION: Our results suggest
      that the postural responses of children with DCD differ from those of typically
      developing children while engaging in a memory task with various levels of
      difficulty.

PMID- 21883172
TI  - Wearable wrist activity monitor as an indicator of functional hand use in
      children with cerebral palsy.

PMID- 21883173
TI  - Immune-mediated steroid-responsive epileptic spasms and epileptic encephalopathy
      associated with VGKC-complex antibodies.
AB  - Autoantibodies that bind to voltage-gated potassium-channel complex proteins
      (VGKC-complex antibodies) occur frequently in adults with limbic encephalitis
      presenting with cognitive impairment and seizures. Recently, VGKC-complex
      antibodies have been described in a few children with limbic encephalitis, and
      children with unexplained encephalitis presenting with status epilepticus. We
      report a case of infantile-onset epileptic spasms and developmental delay
      compatible with epileptic encephalopathy. Our patient was a female infant, aged 4
      months at presentation. She had evidence of immune activation in the central
      nervous system with elevated cerebrospinal fluid neopterin and mirrored
      oligoclonal bands, which prompted testing for autoantibodies. VGKC-complex
      antibodies were elevated (201 pmol/L, normal<100), but extended antibody testing,
      including leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated
      protein 2 (CASPR2), was negative. The patient showed a partial response to
      steroid treatment, which was started late in the disease course. On review at 13
      months of age, her development was consistent with an age of 5 to 6 months. These
      results suggest that VGKC-complex antibodies might represent a marker of immune
      therapy responsiveness in a subgroup of patients with infantile epileptic
      encephalopathy.

PMID- 21883174
TI  - Autonomic effects of refractory epilepsy on heart rate variability in children:
      influence of intermittent vagus nerve stimulation.
AB  - AIM: Vagus nerve stimulation (VNS) is a therapeutic option for individuals with
      refractory epilepsy. Individuals with refractory epilepsy are prone to
      dysfunction of the autonomic nervous system. Reduced heart rate variability is a
      marker of dysfunction of the autonomic nervous system. Our goal was to study
      heart rate variability in children with refractory epilepsy and the influence of
      VNS on this parameter. METHODS: In 17 children (13 male; four female; mean age 7
      y 6 mo; age range 3-16 y) with refractory epilepsy, electroencephalographic and
      electrocardiographic data were obtained before and after implantation of VNS
      during stage 2 and slow-wave sleep. Time and frequency domain parameters were
      calculated and the results were compared with an age- and sex-matched group of
      individuals without refractory epilepsy. RESULTS: Our results show that autonomic
      cardiac control is affected in individuals with refractory epilepsy. There is a
      striking reduction in vagal tone during slow-wave sleep and modulation capacity
      is smaller than in individuals without refractory epilepsy. Implantation of VNS
      induces a shift in sympathovagal balance towards sympathetic predominance and an
      improvement in autonomic modulation. INTERPRETATION: Heart rate variability is
      affected in children with refractory epilepsy, and changes after implantation of
      VNS. The observed changes could be of importance in the cardiac complications of
      individuals with epilepsy and should be explored in more detail.

PMID- 21883175
TI  - Comprehensive analysis of candidate genes for photosensitivity using a
      complementary bioinformatic and experimental approach.
AB  - Photoparoxysmal response (PPR) is a highly heritable electroencephalographic
      trait characterized by an increased sensitivity to photic stimulation. It may
      serve as an endophenotype for idiopathic generalized epilepsy. Family linkage
      studies identified susceptibility loci for PPR on chromosomes 5q35.3, 8q21.13,
      and 16p13.3. This study aimed to identify key candidate genes within these loci.
      We used bioinformatics tools for gene prioritization integrating information on
      biologic function, sequence data, gene expression, and others. The prime
      candidate gene from this analysis was sequenced in 48 photopositive probands.
      Presumed functional implications of identified polymorphisms were investigated
      using bioinformatics methods. The glutamate receptor subunit gene GRIN2A was
      identified as a prime candidate gene. Sequence analysis revealed various new
      polymorphisms. None of the identified variants was predicted to be functionally
      relevant. We objectified the selection of candidate genes for PPR without an a
      priori hypothesis. Particularly among the various ion channel genes in the
      linkage regions, GRIN2A was identified as the prime candidate gene. GRIN2A
      mutations have recently been identified in various epilepsies. Even though our
      mutation analysis failed to demonstrate direct involvement of GRIN2A in
      photosensitivity, in silico gene prioritization may provide a useful tool for the
      identification of candidate genes within large genomic regions.

PMID- 21883176
TI  - Theory of mind in frontal and temporal lobe epilepsy: cognitive and neural
      aspects.
AB  - PURPOSE: Theory of mind (ToM) is an important prerequisite to social behavior.
      This study evaluated ToM in patients with temporal (TLE) or frontal lobe epilepsy
      (FLE) aiming to determine the cognitive aspects, severity, and pathophysiologic
      mechanisms of ToM impairment in focal epilepsy. METHODS: One hundred thirty-eight
      patients with TLE (n = 109) or FLE (n = 29) and 69 healthy subjects underwent the
      Faux Pas task (FPT), which evaluates the recognition and comprehension of others'
      mental states, and neuropsychological tests for other cognitive functions. KEY
      FINDINGS: Factor analysis of all test scores yielded two ToM factors (Recognizing
      faux pas, FP; Excluding nonexistent FP) distinct from the Control, Language,
      Matching, and Praxis factors. With respect to healthy subjects, both TLE and FLE
      patients showed correct exclusion of nonexistent FPs but significantly lower
      recognition and comprehension of real FPs. FLE patients were also impaired with
      respect to TLE patients. In the whole patient group, schooling and group
      membership predicted ToM impairment. In FLE patients, the comprehension of mental
      states was predicted by disease duration, whereas TLE patients' comprehension of
      affects and intentions was associated with early age of seizure onset and medial
      temporal lobe sclerosis (MTLS). SIGNIFICANCE: Focal epilepsy impairs advanced ToM
      abilities. FLE may affect online performances owing to long-lasting dysfunctions
      of the prefrontal areas. MTLS may provoke selective ToM deficits due to medial
      temporal damage, prefrontal dysfunctions, or early interference with cognitive
      development. Future studies are needed to determine the implications of ToM
      impairment on behavior and quality of life.

PMID- 21883177
TI  - Predictors of health-related quality of life and costs in adults with epilepsy: a
      systematic review.
AB  - PURPOSE: Given the high burden of epilepsy on both health-related quality of life
      (HRQoL) and costs, identification of factors that are predictive of either
      reduced HRQoL or increased expenditure is central to the better future targeting
      and optimization of existing and emerging interventions and management strategies
      for epilepsy. METHODS: Searches of Medline, Embase, and Cochrane Library (up to
      July 2010) to identify studies examining the association between demographic,
      psychosocial, and condition-related factors and HRQoL, resource utilization or
      costs in adults with epilepsy. For each study, predictor factor associations were
      summarized on the basis of statistical significance and direction; the results
      were then combined across studies. KEY FINDINGS: Ninety-three HRQoL and 16
      resource utilization/cost studies were included. Increases in seizure frequency,
      seizure severity, level of depression, and level of anxiety and presence of
      comorbidity were strongly associated with reduced HRQoL. The majority of studies
      were cross-sectional in design and had an overall methodologic quality that was
      judged to be "moderate" for HRQoL studies and "poor" for health care resource or
      costs studies. In the 53 multivariate studies, age, gender, marital status, type
      of seizure, age at diagnosis, and duration of epilepsy did not appear to be
      associated with HRQoL, whereas the predictive influence of educational and
      employment status, number of antiepileptic drugs (AEDs) and AED side effects was
      unclear. The association between predictive factors and HRQoL appeared to be
      consistent across individuals whether refractory or seizures controlled or
      managed by AEDs. There were insufficient multivariate studies (five) to reliably
      comment on the predictors of resource utilization or cost in epilepsy.
      SIGNIFICANCE: In addition to seizure control, effective epilepsy management
      requires the early detection of those most at risk of psychological dysfunction
      and comorbidity, and the targeting of appropriate interventions. There is need
      for more rigorous studies with appropriate multivariate statistical methods that
      prospectively investigate the predictors of HRQoL, resource utilization, and
      costs in epilepsy.

PMID- 21883178
TI  - Incidence of kidney stones with topiramate treatment in pediatric patients.
AB  - PURPOSE: We ran this study to assess the incidence of nephrolithiasis in a group
      of children on topiramate (TPM) therapy for at least 1 year. METHODS: In this
      retrospective observational surveillance study, we reviewed the medical charts of
      children on TPM for at least 1 year seen at the pediatric neurology department
      during the period from 2005 to 2010 at King Fahad Medical City. Children with a
      normal baseline ultrasound report were included. Follow-up ultrasound reports
      after at least 1 year were collected. However, patients with any evidence of
      chronic illness or medications that may affect the kidney functions in addition
      to those who are not compliant with the prescribed dose were excluded. Family
      history of renal stones, symptoms suggestive of urologic disorders, and
      comorbidities were recorded. KEY FINDINGS: Medical charts of 96 children on TPM
      with a mean age of 6.9 (+/-3.8) years were reviewed; 52 (54.2%) of the children
      were male. The follow-up ultrasound showed that five children (5.2%) had
      developed kidney stones. The occurrence of kidney stones was found in four female
      patients (80%) versus one male (20%) (p > 0.05). SIGNIFICANCE: Long-term use of
      TPM may result in increased incidence of asymptomatic kidney stones in the
      pediatric population. Hence, routine baseline and follow-up ultrasound of the
      urinary system should be recommended during the use of TPM in children.

PMID- 21883179
TI  - Altered layer-specific gene expression in cortical samples from patients with
      temporal lobe epilepsy.
AB  - PURPOSE: Neuropathologic investigations frequently reveal the presence of
      architectural cortical dysplasia in patients with temporal lobe epilepsy (TLE),
      sometimes as an isolated finding but more commonly associated with hippocampal
      sclerosis (HS) and white matter abnormalities. The histologic pattern and the
      developmental origin of these alterations are not clear, and their diagnostic
      criteria are poorly defined. The aim of this study was to investigate the
      expression patterns of layer-specific genes in cortical specimens from patients
      with TLE presenting different subtypes of cortical malformations in order to
      elucidate the disorganization of the laminar architecture of such epileptogenic
      abnormalities and provide evidence to enable a more objective neuropathologic
      diagnosis. METHODS: We analyzed the expression patterns of CUX2, RORBETA, ER81,
      NURR1, and CTGF genes, respectively specific markers of layers II-III, IV, V, VI,
      and VIb, in surgical samples by means of in situ hybridization and compared them
      with those observed in control cortices. The pathologic samples included typical
      architectural dysplasia (group 1); temporal lobe sclerosis, a variant of
      architectural dysplasia (group 2); and white matter heterotopic neuronal
      aggregates, namely small lentiform nodules (group 3). These abnormalities may
      have been associated or not with HS. KEY FINDINGS: All of the genes had a laminar
      expression pattern in normal cortices, whereas groups 1 and 2 showed alterations
      mainly involving layers V and VI, and highlighted by the altered distribution of
      ER81- and NURR1-positive cells. The expression of ER81 and NURR1 genes was
      different among the groups, and atypical coexpression of NURR1 and CUX2 mRNA was
      detected in the neurons making up the small lentiform nodules. SIGNIFICANCE:
      These findings indicate that defects in cortical organization involving the
      deeper cortical neurons may be a common etiopathogenic mechanism in group 1 and 2
      cortical dysplasia, whether isolated or associated with HS, and that
      developmental disorders may also be present in the white matter (group 3). They
      also provide evidence that the layer-specific genes can be usefully used to
      investigate the neuropathology of human cortical dysplasia.

PMID- 21883181
TI  - Spike-triggered reaction-time EEG as a possible assessment tool for driving
      ability.
AB  - The impact of interictal epileptic activity (IEA) on driving is a rarely
      investigated issue. We analyzed the impact of IEA on reaction time in a pilot
      study. Reactions to simple visual stimuli (light flash) in the Flash test or
      complex visual stimuli (obstacle on a road) in a modified car driving computer
      game, the Steer Clear, were measured during IEA bursts and unremarkable
      electroencephalography (EEG) periods. Individual epilepsy patients showed slower
      reaction times (RTs) during generalized IEA compared to RTs during unremarkable
      EEG periods. RT differences were approximately 300 ms (p < 0.001) in the Flash
      test and approximately 200 ms (p < 0.001) in the Steer Clear. Prior work
      suggested that RT differences >100 ms may become clinically relevant. This
      occurred in 40% of patients in the Flash test and in up to 50% in the Steer
      Clear. When RT were pooled, mean RT differences were 157 ms in the Flash test (p
      < 0.0001) and 116 ms in the Steer Clear (p < 0.0001). Generalized IEA of short
      duration seems to impair brain function, that is, the ability to react. The
      reaction-time EEG could be used routinely to assess driving ability.

PMID- 21883180
TI  - Febrile infection-related epilepsy syndrome (FIRES): pathogenesis, treatment, and
      outcome: a multicenter study on 77 children.
AB  - PURPOSE: To explore the correlations between treatment modalities and selected
      disease parameters with outcome in febrile infection-related epilepsy syndrome
      (FIRES), a catastrophic epileptic encephalopathy with a yet undefined etiology.
      METHODS: We conducted a retrospective multicenter study on children who had been
      included in eight studies published between November 2001 and July 2010.
      Additional data were retrieved from six of the eight participating centers. KEY
      FINDINGS: The 77 enrolled patients presented with prolonged refractory status
      epilepticus. A preceding febrile infection had been reported in 96% of them.
      Treatment modalities included antiepileptic drugs (a median of six), intravenous
      immunoglobulin (IVIG, 30 patients), steroids (29 patients), burst-suppression
      coma (BSC, 46 patients), and other less conventional agents. There was no
      evidence of efficacy for those treatment modalities except for IVIG (two
      patients), a ketogenic diet (one patient), and a prolonged cycle of barbiturate
      anesthesia coma (one patient). Nine patients (11.7%) died during the acute phase
      of FIRES. Only 12 of the 68 surviving patients (18%) retained normal cognitive
      level, but most of them had learning disabilities. Sixty-three patients (93%) had
      refractory epilepsy at follow-up. Cognitive levels at follow-up were
      significantly associated with duration of BSC (p = 0.005) and younger age at
      FIRES onset (p = 0.02). SIGNIFICANCE: The outcome of FIRES is poor. No
      therapeutic agent was efficacious in shortening the acute phase, with the
      possible exception of a ketogenic diet. Treatment by inducing a prolonged BSC was
      associated with a worse cognitive outcome.

PMID- 21883183
TI  - Insular-opercular seizures manifesting with sleep-related paroxysmal motor
      behaviors: a stereo-EEG study.
AB  - PURPOSE: Sleep-related complex motor seizures are a common feature of nocturnal
      frontal lobe epilepsy. Nevertheless, recent studies also suggest that sleep
      related hypermotor seizures can originate in the insula. The present study
      describes the electroclinical features of eight drug-resistant epileptic patients
      with insular-opercular seizures manifesting with nocturnal complex motor
      seizures. METHODS: Patients underwent a comprehensive presurgical evaluation,
      which included history, interictal electroencephalography (EEG), scalp video-EEG
      monitoring, high-resolution magnetic resonance imaging (MRI), and intracerebral
      recording by stereo-EEG. KEY FINDINGS: Almost all patients reported an initial
      sensation consisting of viscerosensitive or somatosensory symptoms. Ictal
      clinical signs were represented by tonic-dystonic asymmetric posturing and/or
      hyperkinetic automatisms, including bimanual/bipedal activity and ballistic
      movements. Some patients exhibited dysarthric speech, hypersalivation, and apnea.
      Interictal and ictal EEG provided lateralizing information in the majority of
      patients. In three patients, MRI showed a focal anatomical abnormality in the
      insular-opercular region. Stereo-EEG ictal recordings demonstrated that the
      epileptic discharge involved simultaneously the insular cortex and the opercular
      region. Complex motor manifestations appeared when the ictal discharge showed an
      extrainsular spreading to frontomesial regions (cingulum, superior frontal gyrus,
      and supplementary motor area) and/or to internal and neocortical temporal lobe
      structures. Six patients received an insular-opercular cortical resection; three
      of them are seizure free (minimum follow-up 24 months) and in one a marked
      reduction in seizure frequency was obtained. Two patients have been operated on
      recently. Histology revealed a focal cortical dysplasia in three patients. One
      patient excluded from surgery died for sudden unexpected death in epilepsy during
      sleep. SIGNIFICANCE: Our data strengthen the concept that sleep-related complex
      motor attacks can originate in the insula, and provide useful electroclinical
      information to differentiate this localization from those with similar clinical
      characteristics. Furthermore, this study indicates that in these drug-resistant
      patients, surgical treatment represents a highly effective treatment option.

PMID- 21883182
TI  - Rapamycin suppresses axon sprouting by somatostatin interneurons in a mouse model
      of temporal lobe epilepsy.
AB  - PURPOSE: In temporal lobe epilepsy many somatostatin interneurons in the dentate
      gyrus die. However, some survive and sprout axon collaterals that form new
      synapses with granule cells. The functional consequences of gamma-aminobutyric
      acid (GABA)ergic synaptic reorganization are unclear. Development of new methods
      to suppress epilepsy-related interneuron axon sprouting might be useful
      experimentally. METHODS: Status epilepticus was induced by systemic pilocarpine
      treatment in green fluorescent protein (GFP)-expressing inhibitory nerurons (GIN)
      mice in which a subset of somatostatin interneurons expresses GFP. Beginning 24 h
      later, mice were treated with vehicle or rapamycin (3 mg/kg intraperitoneally)
      every day for 2 months. Stereologic methods were then used to estimate numbers of
      GFP-positive hilar neurons per dentate gyrus and total length of GFP-positive
      axon in the molecular layer plus granule cell layer. GFP-positive axon density
      was calculated. The number of GFP-positive axon crossings of the granule cell
      layer was measured. Regression analyses were performed to test for correlations
      between GFP-positive axon length versus number of granule cells and dentate gyrus
      volume. KEY FINDINGS: After pilocarpine-induced status epilepticus, rapamycin-
      and vehicle-treated mice had approximately half as many GFP-positive hilar
      neurons as did control animals. Despite neuron loss, vehicle-treated mice had
      over twice the GFP-positive axon length per dentate gyrus as controls, consistent
      with GABAergic axon sprouting. In contrast, total GFP-positive axon length was
      similar in rapamycin-treated mice and controls. GFP-positive axon length
      correlated most closely with dentate gyrus volume. SIGNIFICANCE: These findings
      suggest that rapamycin suppressed axon sprouting by surviving somatostatin/GFP
      positive interneurons after pilocarpine-induced status epilepticus in GIN mice.
      It is unclear whether the effect of rapamycin on axon length was on interneurons
      directly or secondary, for example, by suppressing growth of granule cell
      dendrites, which are synaptic targets of interneuron axons. The mammalian target
      of rapamycin (mTOR) signaling pathway might be a useful drug target for
      influencing GABAergic synaptic reorganization after epileptogenic treatments, but
      additional side effects of rapamycin treatment must be considered carefully.

PMID- 21883184
TI  - Polymorphisms of the UCP2 gene are associated with body fat distribution and risk
      of abdominal obesity in Spanish population.
AB  - BACKGROUND: Increased accumulation of fat results from an imbalance between
      energy expenditure and intake, being modulated by different environmental and
      genetic factors. Uncoupling proteins (UCPs) are mitochondrial carrier proteins
      able to spend energy generating heat. Therefore, variations in these genes are
      good candidates as potential modulators of body fat accumulation. Our aim was to
      investigate the possible association of genetic variations of the gene codifying
      the UCP2 protein with obesity and fat distribution. DESIGN: We performed a cross
      sectional study in 2367 individuals from two population-based studies from
      different regions of Spain. The Hortega Study included 1436 individuals (693
      women) 21-85 years old, and the Pizarra Study included 931 individuals (584
      women) 18-65 years old. We evaluated three polymorphisms of the UCP2 gene.
      RESULTS: The TT genotype of the rs660339 polymorphism and the AA genotype of the
      rs659366 polymorphism of the UCP2 gene were significantly associated with higher
      waist circumference in the Hortega Study. Furthermore, subjects carrying both
      genotypes (TT+AA) also showed higher central adiposity compared with other
      genotypes. This association was also present in the Pizarra Study. Moreover, in
      the pooled population, we found a stronger association with waist circumference.
      Even, we found association with BMI. Furthermore, rs659366 polymorphism was
      associated with the risk of abdominal obesity (P= 0.04: OR = 1.3; CI = 1.01
      1.67). CONCLUSIONS: Polymorphisms of the UCP2 gene (rs660339 and rs659366) were
      associated with central obesity. This study shows association between the UCP2
      gene and the susceptibility to obesity and body fat distribution in a south
      European population.

PMID- 21883185
TI  - Pattern of adrenal morphology and function in patients with acromegaly.
AB  - BACKGROUND: Acromegaly is well known to induce hypertrophic and hyperplastic
      changes in various organs and is commonly accompanied by arterial hypertension.
      In our study, we assess the adrenal morphology and function in a series of
      patients with acromegaly and possible associations with the activity of the
      disease and arterial hypertension. MATERIALS AND METHODS: Sixty patients with
      acromegaly, admitted to two endocrinology departments in the time period 2005
      2010, were studied prospectively. Basal IGF-1 and growth hormone levels after
      oral glucose tolerance test were used to assess the disease activity. All
      subjects underwent adrenal CT scan, basal adrenal hormonal investigation and
      evaluation with 24-h urinary free cortisol and cortisol levels following low-dose
      dexamethasone suppression test. In 33 acromegalics, the 'modified' saline
      infusion test (MSI), i.e. saline infusion after dexamethasone administration, was
      performed to identify autonomous aldosterone (ALD) secretion. RESULTS: Abnormal
      adrenal morphology was present in 48% of our patients, and a significant
      association was found between the presence of arterial hypertension and adrenal
      morphology. Among patients with adrenal morphological changes, 55% exhibited no
      adrenal secretory hyperactivity, 34% autonomous cortisol, 7% ALD and 4% combined
      autonomous cortisol and ALD secretion, when applying recently proposed modified
      cut-off levels compared to widely used criteria. An increased prevalence of
      autonomous ALD secretion was shown among the subgroup of patients with acromegaly
      tested with MSI. CONCLUSIONS: This study provides evidence of an increased
      prevalence of anatomic and functional adrenal alterations in patients with
      acromegaly; further studies will clarify the importance of evaluating these
      subjects with baseline hormonal investigation along with dynamic testing and
      modified cut-offs.

PMID- 21883186
TI  - Endotoxemia affects citrulline, arginine and glutamine bioavailability.
AB  - BACKGROUND: Sepsis considerably alters the intestinal barrier functions, which in
      turn modify the absorption and bioavailability of nutrients. However, the effects
      of septic shock on aminoacid (AAs) bioavailability are poorly documented. The aim
      of this study was to compare the bioavailability of citrulline, arginine and
      glutamine during endotoxemia. MATERIALS AND METHODS: Thirty-six rats were
      randomised into two groups: control and lipopolysaccharides (LPS). The LPS group
      received an intraperitoneal injection of endotoxins (7.5 mg/kg). After 12 h, each
      group was again randomised into three subgroups, each of which received an oral
      bolus of citrulline, arginine or glutamine (5.7 mmol/kg). Blood samples were
      collected at various times from 0 to 600 min after AA administration. The
      concentrations of citrulline, arginine, glutamine and their metabolites arginine
      and ornithine were measured to determine pharmacokinetic parameters Area Under
      Curve (AUC), C(max) and T(max). RESULTS: The AUC values of citrulline decreased
      in LPS rats [citrulline, control: 761 +/- 67 and LPS: 508 +/- 72 MUmol min/mL (P
      = 0.02)]. Maximum concentrations of citrulline were also significantly decreased
      by endotoxemia (P = 0.01). The pharmacokinetic parameters of arginine and
      glutamine were not significantly modified by endotoxemia. The AUC value of
      arginine from citrulline conversion was diminished in endotoxemic rats. The other
      pharmacokinetic parameters of arginine were not significantly modified after
      arginine or citrulline supply in either group (control or LPS). CONCLUSION:
      Endotoxemia affects the bioavailability of AAs differently according to the amino
      acid considered. This feature may be important for nutritional strategy in ICU
      patients.

PMID- 21883187
TI  - Finite layer method for flow in layered radial two-zone aquifer systems.
AB  - A new finite layer method (FLM) is presented in this paper for transient flow
      analysis in layered radial two-zone aquifer systems. A radial two-zone system is
      an aquifer configuration in which a circular aquifer with finite radius is
      surrounded by a matrix possessing different permeability and storage properties.
      The aquifers can be pumped from fully or partially penetrating wells of
      infinitesimal radius. The trial function for drawdown is obtained through the use
      of piecewise linear correction functions in the present method. The trial
      function can satisfy the continuity conditions of flow and possess an appropriate
      continuity of C(0)  at the two-zone interface. On the basis of Galerkin's method
      and the continuity condition of flow, the finite layer formulation is derived.
      The proposed method can cope with the anisotropy and layered heterogeneity in
      radial two-zone aquifer systems. Several numerical examples are presented to
      verify the validity of the present method through comparison with the analytical
      solution and the numerical results based on the finite difference method, in
      which a test of three-dimensional (3D) flow to a partially penetrating well in
      anisotropic two-zone aquifers is included. Furthermore, an additional application
      in simulating the two-zone flow in aquitard-aquifer systems is presented to
      demonstrate the applicability of FLM in modeling flow in more complex aquifer
      systems.

PMID- 21883188
TI  - Evaluation of vertical variations in hydraulic conductivity in unconsolidated
      sediments.
AB  - Detailed information on vertical variations in hydraulic conductivity (K) is
      essential to describe the dynamics of groundwater movement at contaminated sites
      or as input data used for modeling. K values in high vertical resolution should
      be determined because K tends to be more continuous in the horizontal than in the
      vertical direction. To determine K in shallow unconsolidated sediments and in the
      vertical direction, the recently developed direct-push injection logger can be
      used. The information obtained by this method serves as a proxy for K and has to
      be calibrated to obtain quantitative K values of measured vertical profiles. In
      this study, we performed direct-push soil sampling, sieve analyses and direct
      push slug tests to obtain K values in vertical high resolution. Using the results
      of direct-push slug tests, quantitative K values obtained by the direct-push
      injection logger could be determined successfully. The results of sieve analyses
      provided lower accordance with the logs due to the inherent limitations of the
      sieving method.

PMID- 21883189
TI  - Regional flow simulation in fractured aquifers using stress-dependent parameters.
AB  - A model function relating effective stress to fracture permeability is developed
      from Hooke's law, implemented in the tensorial form of Darcy's law, and used to
      evaluate discharge rates and pressure distributions at regional scales. The model
      takes into account elastic and statistical fracture parameters, and is able to
      simulate real stress-dependent permeabilities from laboratory to field studies.
      This modeling approach gains in phenomenology in comparison to the classical ones
      because the permeability tensors may vary in both strength and principal
      directions according to effective stresses. Moreover this method allows
      evaluation of the fracture porosity changes, which are then translated into
      consolidation of the medium.

PMID- 21883190
TI  - Slug test in confined aquifers, the over-damped case: quasi-steady flow analysis.
AB  - In the great majority of slug tests performed in wells fully penetrating confined
      geologic formations, and for over-damped conditions, the response data are
      evaluated with the transient-flow model of Cooper et al. (1967) when the radial
      hydraulic conductivity K(r)  and the coefficient of specific storage S(s)  are to
      be estimated. That particular analytical solution, however, is computationally
      involved and awkward to use. Thus, groundwater professionals often use a few pre
      prepared type-curves to fit the data by a rough matching procedure, visually or
      computationally. On the other hand, the method of Hvorslev (1951), which assumes
      the flow to be quasi-steady, is much simpler but yields only K(r)  estimates. In
      this work, we develop a complete quasi-steady flow model that includes a storage
      balance inside the aquifer and allows estimating K(r)  and S(s)  simultaneously,
      through matching of the well response data to a type-curve. The new model
      approximates the model of Cooper et al. closely and has the practical advantage
      that its solution type-curves are generated easily using an electronic
      spreadsheet, so that the optimal fit of data by a type-curve can be readily
      automated.

PMID- 21883191
TI  - Estimation of streambed groundwater fluxes associated with coaster brook trout
      spawning habitat.
AB  - We hypothesized that the spatial distribution of groundwater inflows through
      river bottom sediments is a critical factor associated with the distribution of
      coaster brook trout (a life history variant of Salvelinus fontinalis) spawning
      redds. An 80-m reach of the Salmon Trout River, in the Huron Mountains of the
      upper peninsula of Michigan, was selected to test the hypothesis based on long
      term documentation of coaster brook trout spawning at this site. A monitoring
      well system consisting of 22 wells was installed in the riverbed to measure
      surface and subsurface temperatures over a 13-month period. The array of
      monitoring wells was positioned to span areas where spawning has and has not been
      observed. Over 200,000 total temperature measurements were collected from five
      depths within each monitoring well. Temperatures in the substrate beneath the
      spawning area were generally less variable than river temperatures, whereas
      temperatures under the nonspawning area were generally more variable and closely
      tracked temporal variations in river temperatures. Temperature data were inverted
      to obtain subsurface groundwater velocities using a numerical approximation of
      the heat transfer equation. Approximately 45,000 estimates of groundwater
      velocities were obtained. Estimated groundwater velocities in the spawning area
      were primarily in the upward direction and were generally greater in magnitude
      than velocities in the nonspawning area. Both the temperature and velocity
      results confirm the hypothesis that spawning sites correspond to areas of
      significant groundwater flux into the river bed.

PMID- 21883193
TI  - Analytical models of steady-state plumes undergoing sequential first-order
      degradation.
AB  - An exact, closed-form analytical solution is derived for one-dimensional (1D),
      coupled, steady-state advection-dispersion equations with sequential first-order
      degradation of three dissolved species in groundwater. Dimensionless and
      mathematical analyses are used to examine the sensitivity of longitudinal
      dispersivity in the parent and daughter analytical solutions. The results
      indicate that the relative error decreases to less than 15% for the 1D advection
      dominated and advection-dispersion analytical solutions of the parent and
      daughter when the Damkohler number of the parent decreases to less than 1 (slow
      degradation rate) and the Peclet number increases to greater than 6 (advection
      dominated). To estimate first-order daughter product rate constants in advection
      dominated zones, 1D, two-dimensional (2D), and three-dimensional (3D) steady
      state analytical solutions with zero longitudinal dispersivity are also derived
      for three first-order sequentially degrading compounds. The closed form of these
      exact analytical solutions has the advantage of having (1) no numerical
      integration or evaluation of complex-valued error function arguments, (2)
      computational efficiency compared to problems with long times to reach steady
      state, and (3) minimal effort for incorporation into spreadsheets. These
      multispecies analytical solutions indicate that BIOCHLOR produces accurate
      results for 1D steady-state, applications with longitudinal dispersion. Although
      BIOCHLOR is inaccurate in multidimensional applications with longitudinal
      dispersion, these multidimensional multispecies analytical solutions indicate
      that BIOCHLOR produces accurate steady-state results when the longitudinal
      dispersion is zero. As an application, the 1D advection-dominated analytical
      solution is applied to estimate field-scale rate constants of 0.81, 0.74, and
      0.69/year for trichloroethene, cis-1,2-dichloroethene, and vinyl chloride,
      respectively, at the Harris Palm Bay, FL, CERCLA site.

PMID- 21883192
TI  - Natural attenuation of septic system nitrogen by anammox.
AB  - On-site disposal of sewage in septic systems can lead to groundwater plumes with
      NO(3)(-)-N concentrations exceeding the common drinking water limit of 10 mg/L.
      Currently, denitrification is considered as the principal natural attenuation
      process. However, at a large seasonal-use septic system in Ontario (256
      campsites), a suboxic zone exists where nitrogen removal of up to 80% occurs
      including removal of NH(4)(+)-N. This zone has both NO(3)(-)-N and NH(4)(+)-N at
      >5 mg/L each. In the distal NH(4)(+)-rich zone, NH(4)(+)-N concentrations (8.1 +/
      8.0 mg/L) are lower than in the proximal zone (48 +/- 36 mg/L) and NH(4)(+)-N is
      isotopically enriched (concentration-weighted mean delta(15)N of +15.70/00)
      compared to the proximal zone (+7.80/00). Furthermore, delta(15)N-NH(4)(+)
      isotopic enrichment increases with depth in the distal zone, which is opposite to
      what would result if nitrification along the water table zone was the mechanism
      causing NH(4)(+) depletion. Bacterial community composition was assessed with
      molecular (DNA-based) analysis and demonstrated that groundwater bacterial
      populations were predominantly composed of bacteria from two Candidatus genera of
      the Planctomycetales (Brocadia and Jettenia). Together, these data provide strong
      evidence that anaerobic ammonium oxidation (anammox) plays an important role in
      nitrogen attenuation at this site.

PMID- 21883194
TI  - Comparison of approaches for predicting solute transport: sandbox experiments.
AB  - The main purpose of this paper was to compare three approaches for predicting
      solute transport. The approaches include: (1) an effective
      parameter/macrodispersion approach (Gelhar and Axness 1983); (2) a heterogeneous
      approach using ordinary kriging based on core samples; and (3) a heterogeneous
      approach based on hydraulic tomography. We conducted our comparison in a
      heterogeneous sandbox aquifer. The aquifer was first characterized by taking 48
      core samples to obtain local-scale hydraulic conductivity (K). The spatial
      statistics of these K values were then used to calculate the effective
      parameters. These K values and their statistics were also used for kriging to
      obtain a heterogeneous K field. In parallel, we performed a hydraulic tomography
      survey using hydraulic tests conducted in a dipole fashion with the drawdown data
      analyzed using the sequential successive linear estimator code (Yeh and Liu 2000)
      to obtain a K distribution (or K tomogram). The effective parameters and the
      heterogeneous K fields from kriging and hydraulic tomography were used in forward
      simulations of a dipole conservative tracer test. The simulated and observed
      breakthrough curves and their temporal moments were compared. Results show an
      improvement in predictions of drawdown behavior and tracer transport when the K
      tomogram from hydraulic tomography was used. This suggests that the high
      resolution prediction of solute transport is possible without collecting a large
      number of small-scale samples to estimate flow and transport properties that are
      costly to obtain at the field scale.

PMID- 21883195
TI  - Modeling fresh water lens damage and recovery on atolls after storm-wave
      washover.
AB  - The principal natural source of fresh water on scattered coral atolls throughout
      the tropical Pacific Ocean is thin unconfined groundwater lenses within islet
      substrates. Although there are many threats to the viability of atoll fresh water
      lenses, salinization caused by large storm waves washing over individual atoll
      islets is poorly understood. In this study, a mathematical modeling approach is
      used to examine the immediate responses, longer-term behavior, and subsequent
      (partial) recovery of a Pacific atoll fresh water lens after saline damage caused
      by cyclone-generated wave washover under different scenarios. Important findings
      include: (1) the saline plume formed by a washover event mostly migrates downward
      first through the top coral sand and gravel substrate, but then exits the aquifer
      to the ocean laterally through the more permeable basement limestone; (2) a lower
      water table position before the washover event, rather than a longer duration of
      storm washover, causes more severe damage to the fresh water lens; (3) relatively
      fresher water can possibly be found as a preserved horizon in the deeper part of
      an aquifer after disturbance, especially if the fresh water lens extends into the
      limestone under normal conditions; (4) post-cyclone accumulation of sea water in
      the central depression (swamp) of an atoll islet prolongs the later stage of
      fresh water lens recovery.

PMID- 21883196
TI  - Migraine misdiagnosed as idiopathic intracranial hypertension.
AB  - This article describes a single case of migraine headaches misdiagnosed as
      idiopathic intracranial hypertension in a young woman. The implications of such a
      diagnosis are discussed. Literature regarding normal intracranial pressure is
      reviewed.

PMID- 21883197
TI  - OnabotulinumtoxinA for treatment of chronic migraine: pooled analyses of the 56
      week PREEMPT clinical program.
AB  - OBJECTIVE: To evaluate safety and efficacy of onabotulinumtoxinA (BOTOX((r)) ) as
      headache prophylaxis in adults with chronic migraine. BACKGROUND: Chronic
      migraine is a prevalent, disabling, and undertreated neurological disorder.
      OnabotulinumtoxinA is the only approved prophylactic therapy in this highly
      disabled patient population. DESIGN AND METHODS: Two phase III, 24-week, double
      blind, parallel-group, placebo-controlled studies, followed by a 32-week, open
      label, single-treatment, onabotulinumtoxinA phase, were conducted (January 23,
      2006 to August 11, 2008). Qualified subjects were randomized (1:1) to injections
      of onabotulinumtoxinA (155-195 U) or placebo every 12 weeks for 5 cycles (double
      blind: 2, open-label: 3). The pooled primary variable was mean change from
      baseline in frequency of headache days. Secondary variables included proportion
      of patients with severe Headache Impact Test-6 score (>= 60) and mean changes
      from baseline in frequencies of migraine days, moderate/severe headache days, and
      migraine episodes; cumulative hours of headache on headache days; and acute
      headache medication intakes. The primary time point was week 24. Assessments for
      the open-label phase (all patients treated with onabotulinumtoxinA) compared
      double-blind treatment groups (onabotulinumtoxinA/onabotulinumtoxinA vs
      placebo/onabotulinumtoxinA) and are summarized to give a descriptive view of
      consistent study results, with inferences regarding statistical significance only
      examined for week 56. RESULTS: A total of 1384 patients were randomized to
      onabotulinumtoxinA (n = 688) or placebo (n = 696) in the double-blind phase; 607
      (88.2%) onabotulinumtoxinA/onabotulinumtoxinA and 629 (90.4%)
      placebo/onabotulinumtoxinA patients continued into the open-label phase.
      OnabotulinumtoxinA/onabotulinumtoxinA treatment statistically significantly
      reduced headache-day frequency vs placebo/onabotulinumtoxinA in patients with
      chronic migraine at week 56 (-11.7 onabotulinumtoxinA/onabotulinumtoxinA, -10.8
      placebo/onabotulinumtoxinA; P = .019). Statistically significant reductions also
      favored onabotulinumtoxinA/onabotulinumtoxinA for several secondary efficacy
      variables at week 56, including frequencies of migraine days (-11.2
      onabotulinumtoxinA/onabotulinumtoxinA, -10.3 placebo/onabotulinumtoxinA; P =
      .018) and moderate/severe headache days (-10.7
      onabotulinumtoxinA/onabotulinumtoxinA, -9.9 placebo/onabotulinumtoxinA; P = .027)
      and cumulative headache hours on headache days (-169.1
      onabotulinumtoxinA/onabotulinumtoxinA, -145.7 placebo/onabotulinumtoxinA; P =
      .018). After the open-label phase (all treated with onabotulinumtoxinA),
      statistically significant within-group changes from baseline were observed for
      all efficacy variables. Most patients (72.6%) completed the open-label phase; few
      discontinued because of adverse events. No new safety or tolerability issues
      emerged. CONCLUSIONS: Repeated treatment with <= 5 cycles of onabotulinumtoxinA
      was effective, safe, and well tolerated in adults with chronic migraine.

PMID- 21883198
TI  - Aspirin is first-line treatment for migraine and episodic tension-type headache
      regardless of headache intensity.
AB  - OBJECTIVES: (1) To establish whether pre-treatment headache intensity in migraine
      or episodic tension-type headache (ETTH) predicts success or failure of treatment
      with aspirin; and (2) to reflect, accordingly, on the place of aspirin in the
      management of these disorders. BACKGROUND: Stepped care in migraine management
      uses symptomatic treatments as first-line, reserving triptans for those in whom
      this proves ineffective. Stratified care chooses between symptomatic therapy and
      triptans as first-line on an individual basis according to perceived illness
      severity. We questioned the 2 assumptions underpinning stratified care in
      migraine that greater illness severity: (1) reflects greater need; and (2) is a
      risk factor for failure of symptomatic treatment but not of triptans. METHODS:
      With regard to the first assumption, we developed a rhetorical argument that need
      for treatment is underpinned by expectation of benefit, not by illness severity.
      To address the second, we reviewed individual patient data from 6 clinical trials
      of aspirin 1000 mg in migraine (N = 2079; 1165 moderate headache, 914 severe) and
      one of aspirin 500 and 1000 mg in ETTH (N = 325; 180 moderate, 145 severe),
      relating outcome to pre-treatment headache intensity. RESULTS: In migraine, for
      headache relief at 2 hours, a small (4.7%) and non-significant risk difference
      (RD) in therapeutic gain favored moderate pain; for pain freedom at 2 hours,
      therapeutic gains were almost identical (RD: -0.2%). In ETTH, for headache relief
      at 2 hours, RDs for both aspirin 500 mg (-4.2%) and aspirin 1000 mg (-9.7%)
      favored severe pain, although neither significantly; for pain freedom at 2 hours,
      RDs (-14.2 and -3.6) again favored severe pain. CONCLUSION: In neither migraine
      nor ETTH does pre-treatment headache intensity predict success or failure of
      aspirin. This is not an arguable basis for stratified care in migraine. In both
      disorders, aspirin is first-line treatment regardless of headache intensity.

PMID- 21883199
TI  - Nighttime blood pressure in cluster headache.
AB  - BACKGROUND: It has been proposed that desaturation of oxygen during an apnea
      event is the trigger for cluster headache. Obstructive sleep apnea has been
      associated with a higher than normal cardiovascular morbidity and mortality. Some
      obstructive sleep apnea syndrome patients lack the sleep-related, nocturnal
      decrease, or "dip" in blood pressure, which is seen in normal individuals.
      OBJECTIVE: The aim of this study is to assess whether this non-dipper pattern is
      present in cluster headache patients. DESIGN AND METHODS: A total of 30
      normotensive cluster headache patients underwent an ambulatory blood pressure
      monitoring. "Non dippers" were defined as patients with a nighttime mean blood
      pressure fall <10%. RESULTS: Fifteen cluster headache patients (50%) were non
      dippers, a frequency higher than expected. The pattern of nocturnal non-dipping
      is associated with a higher body mass index. Non-dipper patients displayed higher
      mean nighttime systolic and diastolic blood pressure. No significant difference
      was observed in the mean 24-hour and daytime blood pressure. CONCLUSIONS: The
      high incidence (50%) of non-dipper pattern in both processes, cluster headache
      and obstructive sleep apnea syndrome, provides support for the hypothesis of a
      relationship between theses 2 disorders.

PMID- 21883200
TI  - Sumatriptan-naproxen migraine efficacy in allodynic patients: early intervention.
AB  - OBJECTIVE: This study evaluated the effectiveness of a single fixed-dose tablet
      of sumatriptan 85 mg/naproxen sodium 500 mg (sumatriptan-naproxen) using a very
      early treatment paradigm in migraine patients whose attacks were historically
      accompanied by cutaneous allodynia. BACKGROUND: Evidence suggests that allodynic
      migraineurs may demonstrate a better response when treated prior to developing
      central sensitization, and that these patients are treated more effectively with
      a compound of sumatriptan and naproxen sodium than either drug alone. This study
      targeted patients who have accompanying allodynia using a very early treatment
      paradigm where treatment was initiated while symptoms were still mild. METHODS:
      This was an open-label prospective, outpatient study of adult migraineurs who had
      screened positive for cutaneous allodynia and typically experienced moderate to
      severe pain preceded by an identifiable mild pain phase. Patients were treated
      with sumatriptan-naproxen using a very early intervention paradigm in 4 test
      migraines over 12 weeks where dosage occurred within 30 minutes of symptom onset.
      Data from diaries and questionnaires were used to evaluate the primary endpoints
      of sustained pain-free response at 24 hours post dose (using no second dose of
      study drug and no other rescue drugs), and overall satisfaction with sumatriptan
      naproxen. RESULTS: Forty allodynic migraineurs enrolled in this study and
      reported a total of 160 migraines. Of these migraines, 78 (49%) achieved
      sustained pain-free at 24 hours and 94 (59%) were reported as pain-free at 2
      hours. The number of patients who rated their Overall Satisfaction following
      treatment with sumatriptan-naproxen as "Satisfied" (satisfied or very satisfied)
      was 32 (80%) after the first migraine and 25 (63%) after 3 or more migraines.
      CONCLUSIONS: In this open-label study, allodynic patients reported that their
      migraine attacks responded well and they achieved a high degree of satisfaction
      following treatment with a fixed-dose tablet of sumatriptan 85 mg/naproxen sodium
      500 mg administered in a very early treatment paradigm.

PMID- 21883202
TI  - Bayesian inference on age-specific survival for censored and truncated data.
AB  - 1. Traditional estimation of age-specific survival and mortality rates in
      vertebrates is limited to individuals with known age. Although this subject has
      been studied extensively using effective capture-recapture and capture-recovery
      models, inference remains challenging because of large numbers of incomplete
      records (i.e. unknown age of many individuals) and because of the inadequate
      duration of the studies. 2. Here, we present a hierarchical model for capture
      recapture/recovery (CRR) data sets with large proportions of unknown times of
      birth and death. The model uses a Bayesian framework to draw inference on
      population-level age-specific demographic rates using parametric survival
      functions and applies this information to reconstruct times of birth and death
      for individuals with unknown age. 3. We simulated a set of CRR data sets with
      varying study span and proportions of individuals with known age, and varying
      recapture and recovery probabilities. We used these data sets to compare our
      method to a traditional CRR model, which requires knowledge of individual ages.
      Subsequently, we applied our method to a subset of a long-term CRR data set on
      Soay sheep. 4. Our results show that this method performs better than the common
      CRR model when sample sizes are low. Still, our model is sensitive to the choice
      of priors with low recapture probability and short studies. In such cases, priors
      that overestimate survival perform better than those that underestimate it. Also,
      the model was able to estimate accurately ages at death for Soay sheep, with an
      average error of 0.94 years and to identify differences in mortality rate between
      sexes. 5. Although many of the problems in the estimation of age-specific
      survival can be reduced through more efficient sampling schemes, most ecological
      data sets are still sparse and with a large proportion of missing records. Thus,
      improved sampling needs still to be combined with statistical models capable of
      overcoming the unavoidable limitations of any fieldwork. We show that our
      approach provides reliable estimates of parameters and unknown times of birth and
      death even with the most incomplete data sets while being flexible enough to
      accommodate multiple recapture probabilities and covariates.

PMID- 21883201
TI  - A quantitative analysis of transcriptionally active syncytiotrophoblast nuclei
      across human gestation.
AB  - The syncytiotrophoblast (STB) epithelial covering of the human placenta is a
      unique terminally differentiated, multi-nucleated syncytium. No mitotic bodies
      are observed in the STB, which is sustained by continuous fusion of underlying
      cytotrophoblast cells (CTB). As a result, STB nuclei are of different ages.
      Morphologically, they display varying degrees of chromatin compaction, suggesting
      progressive maturational changes. Until recently, it was thought that STB nuclei
      were transcriptionally inactive, with all the mRNAs required by the syncytium
      being incorporated upon fusion of CTB. However, recent research has shown the
      presence of the active form of RNA polymerase II (RNA Pol II) in some STB nuclei.
      In this study, we confirm the presence of transcriptional activity in STB nuclei
      by demonstrating immunoreactivity for a transcription factor and an RNA
      polymerase I (RNA Pol I) co-factor, phospho-cAMP response element-binding protein
      and phospho-upstream binding factor, respectively. We also show, through immunoco
      localisation studies, that a proportion of STB nuclei are both RNA Pol I and II
      transcriptionally active. Finally, we quantify the numerical densities of nuclei
      immunopositive and immunonegative for RNA Pol II in the STB of normal placentas
      of 11-39 weeks gestational age using an unbiased stereological counting tool, the
      physical disector. These data were combined with estimates of the volume of
      trophoblast to calculate total numbers of both types of nuclei at each
      gestational age. We found no correlation between gestational age and the
      numerical density of RNA Pol II-positive nuclei in the villous trophoblast (r =
      0.39, P > 0.05). As the number of STB nuclei increases exponentially during
      gestation, we conclude that the number of transcriptionally active nuclei
      increases in proportion to trophoblast volume. The ratio of active to inactive
      nuclei remains constant at 3.9:1. These findings confirm that the majority of STB
      nuclei have intrinsic transcriptional activity, and that the STB is not dependent
      on CTB fusion for the provision of transcripts.

PMID- 21883203
TI  - Trophic links between functional groups of arable plants and beetles are stable
      at a national scale.
AB  - 1. There is an urgent need to accurately model how environmental change affects
      the wide-scale functioning of ecosystems, but advances are hindered by a lack of
      knowledge of how trophic levels are linked across space. It is unclear which
      theoretical approach to take to improve modelling of such interactions, but
      evidence is gathering that linking species responses to their functional traits
      can increase understanding of ecosystem dynamics. Currently, there are no
      quantitative studies testing how this approach might improve models of multiple,
      trophically interacting species, at wide spatial scales. 2. Arable weeds play a
      foundational role in linking food webs, providing resources for many taxa,
      including carabid beetles that feed on their seeds and weed-associated
      invertebrate prey. Here, we model associations between weeds and carabids across
      farmland in Great Britain (GB), to test the hypothesis that wide-scale trophic
      links between these groups are structured by their species functional traits. 3.
      A network of c. 250 arable fields, covering four crops and most lowland areas of
      GB, was sampled for weed, carabid and invertebrate taxa over 3 years. Data sets
      of these groups were closely matched in time and space, and each contained
      numerous species with a range of eco-physiological traits. The consistency of
      trophic linkages between multiple taxa sharing functional traits was tested
      within multivariate and log-linear models. 4. Robust links were established
      between the functional traits of taxa and their trophic interactions. Autumn
      germinating, small-seeded weeds were associated with smaller, spring-breeding
      carabids, more specialised in seed feeding, whereas spring-germinating, large
      seeded weeds were associated with a range of larger, autumn-breeding omnivorous
      carabids. These relationships were strong and dynamic, being independent of
      changes in invertebrate food resources and consistent across sample dates, crops
      and regions of GB. 5. We conclude that, in at least one system of interacting
      taxa, functional traits can be used to predict consistent, wide-scale trophic
      links. This conceptual approach is useful for assessing how perturbations
      affecting lower trophic levels are ramified throughout ecosystems and could be
      used to assess how environmental change affects a wider range of secondary
      consumers.

PMID- 21883204
TI  - A randomized controlled trial of preschool-based joint attention intervention for
      children with autism.
AB  - BACKGROUND: Deficits in joint attention (JA) and joint engagement (JE) represent
      a core problem in young children with autism as these affect language and social
      development. Studies of parent-mediated and specialist-mediated JA-intervention
      suggest that such intervention may be effective. However, there is little
      knowledge about the success of the intervention when done in preschools. AIM:
      Assess the effects of a preschool-based JA-intervention. METHODS: 61 children (48
      males) with autistic disorder (29-60 months) were randomized to either 8 weeks of
      JA-intervention, in addition to their preschool programs (n = 34), or to
      preschool programs only (n = 27). The intervention was done by preschool teachers
      with weekly supervision by trained counselors from Child and Adolescent Mental
      Health Clinics (CAMHC). Changes in JA and JE were measured by blinded independent
      testers using Early Social Communication Scale (ESCS) and video taped preschool
      teacher-child and mother-child play at baseline and post-intervention. CLINICAL
      TRIALS REGISTRATION: Clinicaltrials.gov: NCT00378157. RESULTS: Intention-to-treat
      analysis showed significant difference between the intervention and the control
      group, with the intervention group yielding more JA initiation during interaction
      with the preschool teachers. The effect generalized to significantly longer
      duration of JE with the mothers. CONCLUSIONS: This is the first randomized study
      to show positive and generalized effects of preschool-based JA-intervention.

PMID- 21883206
TI  - Persisting mental health problems among AIDS-orphaned children in South Africa.
AB  - BACKGROUND:   By 2008, 12 million children in sub-Saharan Africa were orphaned by
      AIDS. Cross-sectional studies show psychological problems for AIDS-orphaned
      children, but until now no longitudinal study has explored enduring psychological
      effects of AIDS-orphanhood in the developing world. METHODS:   A 4-year
      longitudinal follow-up of AIDS-orphaned children with control groups of other
      orphans and non-orphans. 1021 children (M = 13.4 years, 50% female, 98% isiXhosa
      speaking) were interviewed in 2005 and followed up in 2009 with 71% retention
      (49% female, M = 16.9 years), in poor urban South African settlements. Children
      were interviewed using sociodemographic questionnaires and well-validated
      standardised scales for assessing depression, anxiety, and post-traumatic stress.
      Data were analysed using mixed-design ANOVA and backward-stepping regression.
      RESULTS:   AIDS-orphaned children showed higher depression, anxiety, and post
      traumatic stress disorder (PTSD) scores in both 2005 and 2009 when compared with
      other-orphans and non-orphans. Backward-stepping regression, controlling for
      baseline mental health, and sociodemographic cofactors such as age, gender, and
      type of bereavement, revealed that being AIDS-orphaned in 2005 was associated
      with depression, anxiety, and PTSD scores in 2009. This was not the case for
      other-orphaned or non-orphaned children. Age interacted with orphan status, such
      that there was a steep rise in psychological distress in the AIDS-orphaned group,
      but no rise with age amongst other-orphans and non-orphans. CONCLUSIONS:  
      Negative mental health outcomes amongst AIDS-orphaned children are maintained and
      worsen over a 4-year period. It is important that psychosocial support programmes
      are sustained, and focus on youth as well as young children.

PMID- 21883207
TI  - Quantification of human mitochondrial DNA using synthesized DNA standards.
AB  - Successful mitochondrial DNA (mtDNA) forensic analysis depends on sufficient
      quantity and quality of mtDNA. A real-time quantitative PCR assay was developed
      to assess such characteristics in a DNA sample, which utilizes a duplex,
      synthetic DNA to ensure optimal quality assurance and quality control. The
      assay's 105-base pair target sequence facilitates amplification of degraded DNA
      and is minimally homologous to nonhuman mtDNA. The primers and probe hybridize to
      a region that has relatively few sequence polymorphisms. The assay can also
      identify the presence of PCR inhibitors and thus indicate the need for sample
      repurification. The results show that the assay provides information down to 10
      copies and provides a dynamic range spanning seven orders of magnitude.
      Additional experiments demonstrated that as few as 300 mtDNA copies resulted in
      successful hypervariable region amplification, information that permits sample
      conservation and optimized downstream PCR testing. The assay described is rapid,
      reliable, and robust.

PMID- 21883205
TI  - Combining information from multiple sources for the diagnosis of autism spectrum
      disorders for toddlers and young preschoolers from 12 to 47 months of age.
AB  - BACKGROUND: Purpose of this study was to systematically examine combined use of
      the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation
      Schedule (ADOS) for children under age 4 using newly developed and revised
      diagnostic algorithms. METHODS: Single and combined use of the ADI-R and ADOS
      algorithms were compared to clinical best estimate diagnoses for 435 children
      with autism spectrum disorders (ASD), 113 children with nonspectrum disorders,
      and 47 children with typical development from 12 to 47 months of age. Sequential
      strategies to reach a diagnostic decision by prioritizing administrations of
      instruments were also evaluated. RESULTS: Well-balanced sensitivities and
      specificities above 80% were obtained for ASD diagnoses using both instruments.
      Specificities significantly improved when both instruments were used compared to
      one. Scores that can be used to systematically prioritize administrations of
      instruments were identified. CONCLUSIONS: The ADI-R and ADOS make independent,
      additive contributions to more accurate diagnostic decisions for clinicians
      evaluating toddlers and young preschoolers with ASD. Sequential assessment
      strategies using the scores identified may be appropriate for some children.

PMID- 21883208
TI  - Autofluorescence imaging, an excellent tool for comparative morphology.
AB  - Here we present a set of methods for documenting (exo-)morphology by applying
      autofluorescence imaging. For arthropods, but also for other taxa,
      autofluorescence imaging combined with composite imaging is a fast documentation
      method with high-resolution capacities. Compared to conventional micro- and
      macrophotography, the illumination is much more homogenous, and structures are
      often better contrasted. Applying different wavelengths to the same object can
      additionally be used to enhance distinct structures. Autofluorescence imaging can
      be applied to dried and embedded specimens, but also directly on specimens within
      their storage liquid. This has an enormous potential for the documentation of
      rare specimens and especially type specimens without the need of preparation.
      Also for various fossils, autofluorescence can be used to enhance the contrast
      between the fossil and the matrix significantly, making even smallest details
      visible. 'Life-colour' fluorescence especially is identified as a technique with
      great potential. It provides additional information for which otherwise more
      complex methods would have to be applied. The complete range of differences and
      variations between fluorescence macrophotography and different types of
      fluorescence microscopy techniques are here explored and evaluated in detail.
      Also future improvements are suggested. In summary, autofluorescence imaging is a
      powerful, easy and fast-to-apply tool for morphological studies.

PMID- 21883209
TI  - Analysis and discrimination of electrical tapes: part II. Backings.
AB  - The backings of 90 black electrical tapes were analyzed to evaluate the chemical
      components of these films, the ability of individual techniques to discriminate
      samples, and the ability of the techniques combined to distinguish samples. The
      techniques utilized and their respective discrimination results were
      stereomicroscopy and physical measurements, to include observation of surface
      features of the backing, width, and thickness measurements (c. 64%); Fourier
      transform infrared spectroscopy (FTIR) using a microscope accessory (c. 83%);
      pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS; c. 81%); and scanning
      electron microscopy/energy-dispersive spectroscopy (SEM/EDS; c. 87%). Ninety-four
      percent of the backings were discriminated through this combination of analytical
      methods. Finally, evaluating these results in conjunction with previously
      published data on the analysis of the adhesives from the same set of electrical
      tapes provided an overall discrimination of nearly 96%.

PMID- 21883210
TI  - Identifying threading dislocations in GaN films and substrates by electron
      channelling.
AB  - Electron channelling contrast imaging of threading dislocations in GaN (0002)
      substrates and epitaxial films has been demonstrated using a conventional
      polepiece-mounted backscatter detector in a commercial scanning electron
      microscope. The influence of accelerating voltage and diffraction vector on
      contrast features denoting specific threading dislocation types has been studied.
      As confirmed by coordinated transmission electron microscopy analysis, electron
      channelling contrast imaging contrast features for edge-type threading
      dislocations are spatially smaller than mixed-type threading dislocations in GaN.
      This ability to delineate GaN edge threading dislocations from mixed type was
      also confirmed by defect-selective etch processing using molten MgO/KOH. This
      study validates electron channelling contrast imaging as a nondestructive and
      widely accessible method for spatially mapping and identifying dislocations in
      GaN with wider applicability for other single-crystal materials.

PMID- 21883211
TI  - A steroid modulatory domain in NR2A collaborates with NR1 exon-5 to control NMDAR
      modulation by pregnenolone sulfate and protons.
AB  - NMDA receptor (NMDAR)-mediated excitatory synaptic transmission plays a critical
      role in synaptic plasticity and memory formation, whereas its dysfunction may
      underlie neuropsychiatric and neurodegenerative diseases. The neuroactive steroid
      pregnenolone sulfate (PS) acts as a cognitive enhancer in impaired animals,
      augments LTP in hippocampal slices by enhancing NMDAR activity, and may
      participate in the reduction of schizophrenia's negative symptoms by systemic
      pregnenolone. We report that the effects of PS on NMDAR function are diverse,
      varying with subunit composition and NR1 splice variant. While PS potentiates NR1
      1a/NR2B receptors through a critical steroid modulatory domain in NR2B that also
      modulates tonic proton inhibition, potentiation of the NMDA response is not
      dependent upon relief of such inhibition, a finding that distinguishes it from
      spermine. In contrast, the presence of an NR2A subunit confers enhanced PS
      potentiation at reduced pH, suggesting that it may indeed act like spermine does
      at NR2B-containing receptors. Additional tuning of the NMDAR response by PS comes
      via the N-terminal exon-5 splicing insert of NR1-1b, which regulates the
      magnitude of proton-dependent PS potentiation. For NR2C- and NR2D-containing
      receptors, negative modulation at NR2C receptors is pH-independent (like NR2B)
      while negative modulation at NR2D receptors is pH-dependent (like NR2A). Taken
      together, PS displays a rich modulatory repertoire that takes advantage of the
      structural diversity of NMDARs in the CNS. The differential pH sensitivity of
      NMDAR isoforms to PS modulation may be especially important given the emerging
      role of proton sensors to both learning and memory, as well as brain injury.

PMID- 21883213
TI  - Targeted disruption of neuronal 19S proteasome subunits induces the formation of
      ubiquitinated inclusions in the absence of cell death.
AB  - Proteasome-mediated proteolysis is a major protein degradation mechanism in cells
      and its dysfunction has been implicated in the pathogenesis of several
      neurodegenerative diseases, each with the common features of neuronal death and
      formation of ubiquitinated inclusions found within neurites, the cell body, or
      nucleus. Previous models of proteasome dysfunction have employed pharmacological
      inhibition of the catalytic subunits of the 20S proteasome core, or the genetic
      manipulation of specific subunits resulting in altered proteasome assembly. In
      this study, we report the use of dominant negative subunits of the 19S regulatory
      proteasome complex that mediate the recognition of ubiquitinated substrates as
      well as the removal of the poly-ubiquitin chain. Interestingly, while each mutant
      subunit-induced inclusion formation, like that seen with pharmacological
      inhibition of the 20S proteasome, none was able to induce apoptotic death, or
      trigger activation of macroautophagy, in either dopaminergic cell lines or
      primary cortical neurons. This finding highlights the dissociation between the
      mechanisms of neuronal inclusion formation and the induction of cell death, and
      represents a novel cellular model for Lewy body-like inclusion formation in
      neurons.

PMID- 21883212
TI  - Genetic tracing of the gustatory neural pathway originating from Pkd1l3
      expressing type III taste cells in circumvallate and foliate papillae.
AB  - Polycystic kidney disease 1-like 3 (Pkd1l3) is expressed specifically in sour
      sensing type III taste cells that have synaptic contacts with afferent nerve
      fibers in circumvallate (CvP) and foliate papillae (FoP) located in the posterior
      region of the tongue, although not in fungiform papillae (FuP) or the palate. To
      visualize the gustatory neural pathways that originate from type III taste cells
      in CvP and FoP, we established transgenic mouse lines that express the
      transneuronal tracer wheat germ agglutinin (WGA) under the control of the mouse
      Pkd1l3 gene promoter/enhancer. The WGA transgene was accurately expressed in
      Pkd1l3-expressing type III taste cells in CvP and FoP. Punctate WGA protein
      signals appeared to be detected specifically in type III taste cells but not in
      other types of taste cells. WGA protein was transferred primarily to a subset of
      neurons located in close proximity to the glossopharyngeal (GL) nerve bundles in
      the nodose/petrosal ganglion (NPG). WGA signals were also observed in a small
      population of neurons in the geniculate ganglion (GG). This result demonstrates
      the anatomical connection between taste receptor cells (TRCs) in the FoP and the
      chorda tympani (CT) nerves. WGA protein was further conveyed to neurons in a
      rostro-central subdivision of the nucleus of the solitary tract (NST). These
      findings demonstrate that the approximately 10 kb 5'-flanking region of the mouse
      Pkd1l3 gene functions as a type III taste cell-specific promoter/enhancer. In
      addition, experiments using the pkd1l3-WGA transgenic mice reveal a sour
      gustatory pathway that originates from TRCs in the posterior region of the
      tongue.

PMID- 21883214
TI  - The in vivo neurochemistry of the brain during general anesthesia.
AB  - Anesthesia describes a complex state composed of immobility, amnesia, hypnosis
      (sleep or loss of consciousness), analgesia, and muscle relaxation. Bottom-up
      approaches explain anesthesia by an interaction of the anesthetic with receptor
      proteins in the brain, whereas top-down approaches consider predominantly
      cortical and thalamic network activity and connectivity. Both approaches have a
      number of explanatory gaps and as yet no unifying view has emerged. In addition
      to a direct interaction with primary target receptor proteins, general
      anesthetics have massive effects on neurotransmitter activity in the brain. They
      can change basal transmitter levels by interacting with neuronal activity,
      transmitter synthesis, release, reuptake and metabolism. By that way, they can
      affect a great number of neurotransmitter systems and receptors. Here, we review
      how different general anesthetics affect extracellular activity of
      neurotransmitters in the brain during induction, maintenance, and emergence from
      anesthesia and which functional consequences this may have. Commonalities and
      differences between different groups of anesthetics in their action on
      neurotransmitter activity are discussed. We also review how general anesthetics
      affect the response dynamics of the neurotransmitter systems after sensory
      stimulation. More than 30 years of research have now yielded a complex picture of
      the effects of general anesthetics on brain neurotransmitter basal activity and
      response dynamics. It is suggested that analyzing the effects on neurotransmitter
      activity is the logical next step after protein interactions in a bottom-up
      analysis of anesthetic action in the brain on the way to a unifying view of
      anesthesia.

PMID- 21883215
TI  - Blocking epidermal growth factor receptor attenuates reactive astrogliosis
      through inhibiting cell cycle progression and protects against ischemic brain
      injury in rats.
AB  - Excessive astrogliosis is a major impediment to axonal regeneration in CNS
      disorders. Overcoming this inhibitory barrier of reactive astrocytes might be
      crucial for CNS repair. Up-regulation and activation of epidermal growth factor
      receptor (EGFR) has been shown to trigger quiescent astrocytes into reactive
      astrocytes in response to several neural injuries. In this study, we investigated
      the effects of EGFR blockade in cultured astrocytes exposure to oxygen-glucose
      deprivation/reoxygenation (OGD/R) and in the rat middle cerebral artery occlusion
      (MCAO) model. Astrocytes in primary culture were used for OGD/R model and adult
      male Sprague-Dawley rats were used for MCAO model. Cell cycle progression of
      astrocytes in vitro was studied by flow cytometric analysis. Expression of
      phosphorylated epidermal growth factor receptor (p-EGFR), glial fibrillary acidic
      protein (GFAP), and cell proliferation-related molecules in vitro and in vivo
      were evaluated by immunostaining and western blot analysis. Neuronal apoptosis
      after MCAO was determined by terminal deoxynucleotidyl transferase dUTP nick end
      labeling (TUNEL) method. Neurologic scores and infarct volumes post-ischemia were
      assessed in the rat MCAO model. Astrocytes became activated in the cultured
      astrocytes exposure to OGD/R and in the rat brain after MCAO, accompanied with
      phosphorylation of EGFR. EGFR blockade significantly decreased expression of p
      EGFR, inhibited cell cycle progression of astrocytes, and reduced reactive
      astrogliosis in vitro and in vivo. EGFR inhibition also reduced infarct volumes
      and improved neurologic scores of rats after MCAO. Our findings indicated that
      blocking EGFR pathway might attenuate reactive astrogliosis through inhibiting
      cell cycle progression and protect against ischemic brain injury in rats.

PMID- 21883217
TI  - Dexamethasone-induced up-regulation of the human norepinephrine transporter
      involves the glucocorticoid receptor and increased binding of C/EBP-beta to the
      proximal promoter of norepinephrine transporter.
AB  - Previously, we have found glucocorticoids up-regulate norepinephrine (NE)
      transporter (NET) expression in vitro. However, the underlying transcriptional
      mechanism is poorly understood. In this study, the role of glucocorticoids on the
      transcriptional regulation of NET was investigated. Exposure of neuroblastoma SK
      N-BE(2)M17 cells to dexamethasone (Dex) significantly increased NET mRNA and
      protein levels in a time- and dose-dependent manner. This effect was attenuated
      by glucocorticoid receptor (GR) antagonist mifepristone, suggesting that up
      regulation of NET by Dex was mediated by the GR. In reporter gene assays,
      exposure of cells to Dex resulted in dose-dependent increases of luciferase
      activity that were also prevented by mifepristone. Serial deletions of the NET
      promoter delineated Dex-responsiveness to a -301 to -148 bp region containing a
      CCAAT/enhancer binding protein-beta (C/EBP-beta) response element. Co
      immunoprecipitation experiments demonstrated that Dex treatment caused the
      interaction of the GR with C/EBP-beta. Chromatin immunoprecipitation (ChIP) assay
      revealed that Dex exposure resulted in binding of both GR and C/EBP-beta to the
      NET promoter. Further experiments showed that mutation of the C/EBP-beta response
      element abrogated C/EBP-beta- and GR-mediated transactivation of NET. These
      findings demonstrate that Dex-induced increase in NET expression is mediated by
      the GR via a non-conventional transcriptional mechanism involving interaction of
      C/EBP-beta with a C/EBP-beta response element.

PMID- 21883216
TI  - Dysregulated phosphorylation of Ca(2+) /calmodulin-dependent protein kinase II
      alpha in the hippocampus of subjects with mild cognitive impairment and
      Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive, neurodegenerative disorder and the
      most prevalent senile dementia. The early symptom of memory dysfunction involves
      synaptic loss, thought to be mediated by soluble amyloid-beta (Abeta) oligomers.
      These aggregate species target excitatory synapses and their levels correlate
      with disease severity. Studies in cell culture and rodents have shown that
      oligomers increase intracellular calcium (Ca(2+)), impairing synaptic plasticity.
      Yet, the molecular mechanism mediating Abeta oligomers' toxicity in the aged
      brain remains unclear. Here, we apply quantitative immunofluorescence in human
      brain tissue from clinically diagnosed mild cognitive impaired (MCI) and AD
      patients to investigate the distribution of phosphorylated (active) Ca(2+)
      /calmodulin-dependent protein kinase-alpha (p(Thr286)CaMKII), a critical enzyme
      for activity-dependent synaptic remodeling associated with cognitive function. We
      show that p(Thr286)CaMKII immunoreactivity is redistributed from dendritic
      arborizations to neural perikarya of both MCI and AD hippocampi. This finding
      correlates with cognitive assessment scores, suggesting that it may be a
      molecular read-out of the functional deficits in early AD. Treatment with
      oligomeric Abeta replicated the observed phenotype in mice and resulted in a loss
      of p(Thr286)CaMKII from synaptic spines of primary hippocampal neurons. Both
      outcomes were prevented by inhibiting the phosphatase calcineurin (CaN).
      Collectively, our results support a model in which the synaptotoxicity of Abeta
      oligomers in human brain involves the CaN-dependent subcellular redistribution of
      p(Thr286)CaMKII. Therapies designed to normalize the homeostatic imbalance of
      neuronal phosphatases and downstream dephosphorylation of synaptic
      p(Thr286)CaMKII should be considered to prevent and treat early AD.

PMID- 21883218
TI  - Dual neuroprotective pathways of a pro-electrophilic compound via HSF-1-activated
      heat-shock proteins and Nrf2-activated phase 2 antioxidant response enzymes.
AB  - Activation of the Keap1/nuclear factor erythroid 2-related factor 2 (Nrf2)
      pathway and consequent induction of phase 2 antioxidant enzymes is known to
      afford neuroprotection. Here, we present a series of novel electrophilic
      compounds that protect neurons via this pathway. Natural products, such as
      carnosic acid (CA), are present in high amounts in the herbs rosemary and sage as
      ortho-dihydroquinones, and have attracted particular attention because they are
      converted by oxidative stress to their active form (ortho-quinone species) that
      stimulate the Keap1/Nrf2 transcriptional pathway. Once activated, this pathway
      leads to the production of a series of antioxidant phase 2 enzymes. Thus, such
      dihydroquinones function as redox-activated 'pro-electrophiles'. Here, we
      explored the concept that related para-dihydroquinones represent even more
      effective bioactive pro-electrophiles for the induction of phase 2 enzymes
      without producing toxic side effects. We synthesized several novel para
      hydroquinone-type pro-electrophilic compounds (designated D1 and D2) to analyze
      their protective mechanism. DNA microarray, PCR, and western blot analyses showed
      that compound D1 induced expression of heat-shock proteins (HSPs), including
      HSP70, HSP27, and DnaJ, in addition to phase 2 enzymes such as hemeoxygenase-1
      (HO-1), NADP(H) quinine-oxidoreductase1, and the Na(+)-independent
      cystine/glutamate exchanger (xCT). Treatment with D1 resulted in activation of
      Nrf2 and heat-shock transcription factor-1 (HSF-1) transcriptional elements, thus
      inducing phase 2 enzymes and HSPs, respectively. In this manner, D1 protected
      neuronal cells from both oxidative and endoplasmic reticulum (ER)-related stress.
      Additionally, D1 suppressed induction of 78 kDa glucose-regulated protein
      (GRP78), an ER chaperone protein, and inhibited hyperoxidation of peroxiredoxin 2
      (PRX2), a molecule that is in its reduced state can protect from oxidative
      stress. These results suggest that D1 is a novel pro-electrophilic compound that
      activates both the Nrf2 and HSF-1 pathways, and may thus offer protection from
      oxidative and ER stress.

PMID- 21883219
TI  - Reduced levels of the tyrosine phosphatase STEP block beta amyloid-mediated
      GluA1/GluA2 receptor internalization.
AB  - Striatal-Enriched protein tyrosine Phosphatase of MW 61 kDa (STEP(61)) is a
      protein tyrosine phosphatase recently implicated in the pathophysiology of
      Alzheimer's disease (AD). STEP(61) is elevated in human AD prefrontal cortex and
      in the cortex of several AD mouse models. The elevated levels of active STEP(61)
      down-regulate surface expression of GluN1/GluN2B (formerly NR1/NR2B) receptor
      complexes, while genetically reducing STEP levels rescues both the biochemical
      and cognitive deficits in a triple transgenic AD mouse model (3xTg-AD). Here, we
      show that increased STEP(61) also plays a role in beta amyloid (Abeta)-mediated
      internalization of the alpha-amino-3-hydroxy-5-methyl-4-(AMPA) receptor (AMPAR)
      subunits GluA1/GluA2 (formerly GluR1/GluR2). We purified Abeta oligomers and
      determined that oligomers, but not monomers, lead to endocytosis of GluA1/GluA2
      receptors in cortical cultures. The decrease in GluA1/GluA2 receptors is reversed
      in the progeny of STEP knock-out (KO) mice crossed with Tg2576 mice, despite
      elevated levels of Abeta. These results provide strong support for the hypothesis
      that STEP(61) is required for Abeta-mediated internalization of GluA1/GluA2
      receptors.

PMID- 21883220
TI  - Diabetic neuropathy enhances voltage-activated Ca2+ channel activity and its
      control by M4 muscarinic receptors in primary sensory neurons.
AB  - Painful neuropathy is one of the most serious complications of diabetes and
      remains difficult to treat. The muscarinic acetylcholine receptor (mAChR)
      agonists have a profound analgesic effect on painful diabetic neuropathy. Here we
      determined changes in T-type and high voltage-activated Ca(2+) channels (HVACCs)
      and their regulation by mAChRs in dorsal root ganglion (DRG) neurons in a rat
      model of diabetic neuropathy. The HVACC currents in large neurons, T-type
      currents in medium and large neurons, the percentage of small DRG neurons with T
      type currents, and the Cav3.2 mRNA level were significantly increased in diabetic
      rats compared with those in control rats. The mAChR agonist oxotremorine-M
      significantly inhibited HVACCs in a greater proportion of DRG neurons with and
      without T-type currents in diabetic than in control rats. In contrast,
      oxotremorine-M had no effect on HVACCs in small and large neurons with T-type
      currents and in most medium neurons with T-type currents from control rats. The
      M(2) and M(4) antagonist himbacine abolished the effect of oxotremorine-M on
      HVACCs in both groups. The selective M(4) antagonist muscarinic toxin-3 caused a
      greater attenuation of the effect of oxotremorine-M on HVACCs in small and medium
      DRG neurons in diabetic than in control rats. Additionally, the mRNA and protein
      levels of M(4), but not M(2), in the DRG were significantly greater in diabetic
      than in control rats. Our findings suggest that diabetic neuropathy potentiates
      the activity of T-type and HVACCs in primary sensory neurons. M(4) mAChRs are up
      regulated in DRG neurons and probably account for increased muscarinic analgesic
      effects in diabetic neuropathic pain.

PMID- 21883222
TI  - 'Clinical trials in Alzheimer's disease': immunotherapy approaches.
AB  - Recent advances in the understanding of Alzheimer's disease pathogenesis have led
      to the development of numerous compounds that might modify the disease process.
      Amyloid beta (Abeta) peptide represents an important molecular target for
      intervention in Alzheimer's disease. Several types of Abeta peptide immunotherapy
      for Alzheimer's disease are under investigation, direct immunization with
      synthetic intact Abeta(42) , active immunization involving the administration of
      synthetic fragments of Abeta peptide conjugated to a carrier protein and passive
      administration with monoclonal antibodies directed against Abeta peptide. Pre
      clinical studies showed that immunization against Abeta peptide can provide
      protection and reversal of the pathology of Alzheimer's disease in animal models.
      Indeed, several adverse events have been described like meningoencephalitis with
      AN1792, vasogenic edema and microhemorrhages with bapineuzumab. Although
      immunotherapy approaches resulted in clearance of amyloid plaques in patients
      with Alzheimer's disease, this clearance did not show significant cognitive
      effect for the moment. Currently, several Abeta peptide immunotherapy approaches
      are under investigation but also against tau pathology.

PMID- 21883221
TI  - Knockout of G protein beta5 impairs brain development and causes multiple
      neurologic abnormalities in mice.
AB  - Gbeta5 is a divergent member of the signal-transducing G protein beta subunit
      family encoded by GNB5 and expressed principally in brain and neuronal tissue.
      Among heterotrimeric Gbeta isoforms, Gbeta5 is unique in its ability to
      heterodimerize with members of the R7 subfamily of the regulator of G protein
      signaling proteins that contain G protein-gamma like domains. Previous studies
      employing Gnb5 knockout (KO) mice have shown that Gbeta5 is an essential
      stabilizer of such regulator of G protein signaling proteins and regulates the
      deactivation of retinal phototransduction and the proper functioning of retinal
      bipolar cells. However, little is known of the function of Gbeta5 in the brain
      outside the visual system. We show here that mice lacking Gbeta5 have a markedly
      abnormal neurologic phenotype that includes impaired development, tiptoe-walking,
      motor learning and coordination deficiencies, and hyperactivity. We further show
      that Gbeta5-deficient mice have abnormalities of neuronal development in
      cerebellum and hippocampus. We find that the expression of both mRNA and protein
      from multiple neuronal genes is dysregulated in Gnb5 KO mice. Taken together with
      previous observations from Gnb5 KO mice, our findings suggest a model in which
      Gbeta5 regulates dendritic arborization and/or synapse formation during
      development, in part by effects on gene expression.

PMID- 21883223
TI  - Activation of alpha-secretase cleavage.
AB  - Alpha-secretase-mediated cleavage of the amyloid precursor protein (APP) releases
      the neuroprotective APP fragment salphaAPP and prevents amyloid beta peptide
      (Abeta) generation. Moreover, alpha-secretase-like cleavage of the Abeta
      transporter 'receptor for advanced glycation end products' counteracts the import
      of blood Abeta into the brain. Assuming that Abeta is responsible for the
      development of Alzheimer's disease (AD), activation of alpha-secretase should be
      preventive. alpha-Secretase-mediated APP cleavage can be activated via several G
      protein-coupled receptors and receptor tyrosine kinases. Protein kinase C,
      mitogen-activated protein kinases, phosphatidylinositol 3-kinase, cAMP and
      calcium are activators of receptor-induced alpha-secretase cleavage. Selective
      targeting of receptor subtypes expressed in brain regions affected by AD appears
      reasonable. Therefore, the PACAP receptor PAC1 and possibly the serotonin 5-HT(6)
      receptor subtype are promising targets. Activation of APP alpha-secretase
      cleavage also occurs upon blockade of cholesterol synthesis by statins or
      zaragozic acid A. Under physiological statin concentrations, the brain
      cholesterol content is not influenced. Statins likely inhibit Abeta production in
      the blood by alpha-secretase activation which is possibly sufficient to inhibit
      AD development. A disintegrin and metalloproteinase 10 (ADAM10) acts as alpha
      secretase on APP. By targeting the nuclear retinoic acid receptor beta, the
      expression of ADAM10 and non-amyloidogenic APP processing can be enhanced.
      Excessive activation of ADAM10 should be avoided because ADAM10 and also ADAM17
      are not APP-specific. Both ADAM proteins cleave various substrates, and therefore
      have been associated with tumorigenesis and tumor progression.

PMID- 21883224
TI  - alpha-Synuclein promotes clathrin-mediated NMDA receptor endocytosis and
      attenuates NMDA-induced dopaminergic cell death.
AB  - Abnormalities of alpha-synuclein (alpha-syn) and NMDA receptors (NMDARs) are
      implicated in the pathogenesis of Parkinson's disease. However, how these
      proteins interact with each other has not been elucidated. Here, the effect of
      alpha-syn on NMDARs was investigated by examining the alterations of surface
      NMDAR NR1 subunits in MES23.5 dopaminergic cells transfected with the human alpha
      syn gene as well as in cells treated with extracellularly added human alpha-syn.
      As demonstrated previously that alpha-syn can enter cells in a non-endocytic
      manner without being degraded by the cellular proteolytic systems, the
      extracellularly added alpha-syn entered the cytoplasm of MES23.5 cells in a
      concentration-dependent manner. Both the alpha-syn-transfected cells and alpha
      syn-treated cells exhibited increased intracellular alpha-syn levels and reduced
      surface NR1 without altering the total NR1. The alpha-syn-induced surface NR1
      reduction was accompanied by suppression of NMDA-elicited intracellular Ca(2+)
      elevation and reductions of NMDA-induced caspase 3 activation and cell death,
      which was abolished by hypotonic shock and K(+) depletion, a procedure that
      blocks clathrin-mediated endocytosis, and by suppression of RAB5B expression with
      anti-RAB5B oligonucleotides. The data obtained provide evidence for the first
      time that alpha-syn may promote clathrin-mediated NMDAR endocytosis.

PMID- 21883225
TI  - Amyotrophic lateral sclerosis-immunoglobulins selectively interact with
      neuromuscular junctions expressing P/Q-type calcium channels.
AB  - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease
      characterized by a gradual loss of motoneurons. The majority of ALS cases are
      associated with a sporadic form whose etiology is unknown. Several pieces of
      evidence favor autoimmunity as a potential contributor to sporadic ALS pathology.
      To gain understanding concerning possible antigens interacting with IgGs from
      sporadic ALS patients (ALS-IgGs), we studied immunoreactivity against
      neuromuscular junction (NMJ), spinal cord and cerebellum of mice with and without
      the Ca(V) 2.1 pore-forming subunit of the P/Q-type voltage-gated calcium (Ca(2+))
      channel. ALS-IgGs showed a strong reactivity against NMJs of wild-type
      diaphragms. ALS-IgGs also increased muscle miniature end-plate potential
      frequency, suggesting a functional role for ALS-IgGs on synaptic signaling. In
      support, in mice lacking the Ca(V) 2.1 subunit ALS-IgGs showed significantly
      reduced NMJ immunoreactivity and did not alter spontaneous acetylcholine release.
      This difference in reactivity was absent when comparing N-type Ca(2+) channel
      wild-type or null mice. These results are particularly relevant because
      motoneurons are known to be early pathogenic targets in ALS. Our findings add
      further evidence supporting autoimmunity as one of the possible mechanisms
      contributing to ALS pathology. They also suggest that serum autoantibodies in a
      subset of ALS patients would interact with NMJ proteins down-regulated when P/Q
      type channels are absent.

PMID- 21883226
TI  - Highly conserved tyrosine 37 stabilizes desensitized states and restricts calcium
      permeability of ATP-gated P2X3 receptor.
AB  - Tyrosine 37 in the first transmembrane (TM1) domain is highly conserved in ATP
      gated P2X receptors suggesting its fundamental role. We tested whether Y37
      contributes to the desensitization of P2X3 receptors, which is currently not well
      understood. By combining electrophysiological, imaging and modeling approaches,
      we studied desensitization of various Y37 P2X3 mutants and potential partners of
      Y37. Unlike the membrane current of the WT receptor, which desensitized in
      seconds, Y37A mutant current did not fully desensitize even after minutes-long
      applications of beta,gamma-meATP, alpha,beta-meATP, ATP or 2MeS-ATP. The
      fractional calcium current was enhanced in the Y37A mutant. Y37F did not rescue
      the native P2X3 phenotype indicating a role for the hydroxyl group of Y37 for the
      WT receptor. Homology modeling indicated I318 or I319 in TM2 as potential
      partners for Y37 in the receptor closed state. We tested this hypothesis by
      creating a permanent interaction between the two residues via disulfide bond.
      Whereas single Y37C, I318C and I319C mutants were functional, the double mutants
      Y37C-I318C and Y37C-I319C were non-functional. Using a cyclic model of receptor
      operation, we suggest that the conserved tyrosine 37 links TM1 to TM2 of adjacent
      subunit to stabilize desensitized states and restricts calcium permeability
      through the ion channel.

PMID- 21883227
TI  - Chloroquine inhibits glutamate-induced death of a neuronal cell line by reducing
      reactive oxygen species through sigma-1 receptor.
AB  - Chloroquine, a widely used anti-malarial and anti-rheumatoid agent, has been
      reported to induce apoptotic and non-apoptotic cell death. Accumulating evidence
      now suggests that chloroquine can sensitize cancer cells to cell death and
      augment chemotherapy-induced apoptosis by inhibiting autophagy. However,
      chloroquine is reported to induce GM1 ganglioside accumulation in cultured cells
      at low MUM concentrations and prevent damage to the blood brain barrier in mice.
      It remains unknown whether chloroquine has neuroprotective properties at
      concentrations below its reported ability to inhibit lysosomal enzymes and
      autophagy. In the present study, we demonstrated that chloroquine protected mouse
      hippocampal HT22 cells from glutamate-induced oxidative stress by attenuating
      production of excess reactive oxygen species. The concentration of chloroquine
      required to rescue HT22 cells from oxidative stress was much lower than that
      sufficient enough to induce cell death and inhibit autophagy. Chloroquine
      increased GM1 level in HT22 cells at low MUM concentrations but glutamate-induced
      cell death occurred before GM1 accumulation, suggesting that GM1 induction is not
      related to the protective effect of chloroquine against glutamate-induced cell
      death. Interestingly, BD1047 and NE-100, sigma-1 receptor antagonists, abrogated
      the protective effect of chloroquine against glutamate-induced cell death and
      reactive oxygen species production. In addition, cutamesine (SA4503), a sigma-1
      receptor agonist, prevented both glutamate-induced cell death and reactive oxygen
      species production. These findings indicate that chloroquine at concentrations
      below its ability to inhibit autophagy and induce cell death is able to rescue
      HT22 cells from glutamate-induced cell death by reducing excessive production of
      reactive oxygen species through sigma-1 receptors. These results suggest
      potential use of chloroquine, an established anti-malarial agent, as a
      neuroprotectant against oxidative stress, which occurs in a variety of
      neurodegenerative diseases.

PMID- 21883228
TI  - Ifenprodil restores GDNF-evoked Ca(2+) signalling and Na(+)/K(+) -ATPase
      expression in inflammation-pretreated astrocytes.
AB  - Glial cell line-derived neurotrophic factor (GDNF) plays an important role in
      neuroinflammatory and neuropathic pain conditions. Astrocytes produce and secrete
      GDNF, which interacts with its receptors to induce Ca(2+) transients. This study
      aimed first to assess intracellular Ca(2+) responses of astrocytes in primary
      culture when exposed to the neuroprotective and anti-inflammatory peptide GDNF.
      Furthermore, incubation with the inflammatory inducers lipopolysaccharide (LPS),
      NMDA, or interleukin 1-beta (IL-1beta) attenuated the GDNF-induced Ca(2+)
      transients. The next aim was to try to restore the suppressed GDNF responses
      induced by inflammatory changes in the astrocytes with an anti-inflammatory
      substance. Ifenprodil, an NMDA receptor antagonist at the NR2B subunit, was
      tested. It was shown to restore the GDNF-evoked Ca(2+) transients and increased
      the Na(+)/K(+) -ATPase expression. Ifenprodil seems to be a potent anti
      inflammatory substance for astrocytes which have been pre-activated by
      inflammatory stimuli.

PMID- 21883229
TI  - A novel gene required for natural competence in Aggregatibacter
      actinomycetemcomitans.
AB  - BACKGROUND AND OBJECTIVE: Natural competence is the ability of bacteria to take
      up extracellular DNA and incorporate it into their genomes. Some strains of
      Aggregatibacter actinomycetemcomitans, a critical periodontal pathogen, are
      naturally competent for transformation. However, information on natural
      competence genes is limited for this species. The aim of this study was to
      confirm the involvement of a novel gene identified near the fimbriae gene cluster
      in natural competence. MATERIAL AND METHODS: The functions of putative open
      reading frames (ORFs), designated AA00863-AA00865, in the Oralgen project
      database for A. actinomycetemcomitans strain HK1651, have not been determined.
      Using naturally transformable A. actinomycetemcomitans strains D7S-1 and
      ATCC29523, we created deletion mutants of homologous genes of these ORFs. Natural
      competence in the study strains was determined using an agar-based transformation
      frequency assay. RESULTS: Mutation of the AA00865 homolog, which we named urpA in
      A. actinomycetemcomitans strain D7S-1, resulted in the loss of natural
      competence, whereas mutations of the AA00864 and AA00863 homologs, located
      downstream of urpA gene, did not. Similar results were also observed in the
      mutants of A. actinomycetemcomitans ATCC29523. Complementation of the deleted
      sequence in the urpA mutant restored natural competence. CONCLUSION: The urpA
      gene is a novel gene required for natural competence in A. actinomycetemcomitans
      and does not exhibit significant homology with any natural competence genes
      previously identified in other bacterial species.

PMID- 21883230
TI  - Molecular events associated with ciclosporin A-induced gingival overgrowth are
      attenuated by Smad7 overexpression in fibroblasts.
AB  - BACKGROUND AND OBJECTIVE: Ciclosporin A (CsA)-induced gingival overgrowth is
      attributed to an exaggerated accumulation of extracellular matrix, which is
      mainly due to an increased expression of transforming growth factor-beta1 (TGF
      beta1). Herein, the in vitro investigation of effects of overexpression of Smad7,
      a TGF-beta1 signaling inhibitor, in the events associated with CsA-induced
      extracellular matrix accumulation was performed. MATERIAL AND METHODS: The
      effects of Smad7 were assessed by stable overexpression of Smad7 in fibroblasts
      from normal gingiva. Smad7-overexpressing cells and control cells were incubated
      with CsA, and synthesis of type I collagen, production and activity of MMP-2 and
      cellular proliferation were evaluated by ELISA, zymography, growth curve,
      bromodeoxyuridine incorporation assay and cell cycle analysis. The effects of CsA
      on cell viability and apoptosis of fibroblasts from normal gingiva were also
      evaluated. Western blot and immunofluorescence for phospho-Smad2 were performed
      to measure the activation of TGF-beta1 signaling. RESULTS: Although the treatment
      with CsA stimulated TGF-beta1 production in both control and Smad7-overexpressing
      fibroblasts, its signaling was markedly inhibited in Smad7-overexpressing cells,
      as revealed by low levels of phospho-Smad2. In Smad7-overexpressing cells, the
      effects of CsA on proliferation, synthesis of type I collagen and the production
      and activity of MMP-2 were significantly blocked. Smad7 overexpression blocked
      CsA-induced fibroblast proliferation via p27 regulation. Neither CsA nor Smad7
      overexpression induced cell death. CONCLUSION: The data presented here confirm
      that TGF-beta1 expression is related to the molecular events associated with CsA
      induced gingival overgrowth and suggest that Smad7 overexpression is effective in
      blocking these events, including proliferation, type I collagen synthesis and MMP
      2 activity.

PMID- 21883231
TI  - Ectomycorrhizal fungal diversity and community structure on three co-occurring
      leguminous canopy tree species in a Neotropical rainforest.
AB  - * The ectomycorrhizal (ECM) symbiosis was historically considered restricted to
      the temperate zones, but recent studies have shown the importance of this
      symbiosis across the tropics. We examined ECM fungal diversity, host plant
      phylogeny and ECM host preferences in a rainforest dominated by the leguminous
      host plants Dicymbe corymbosa, Dicymbe altsonii and Aldina insignis. *
      Ectomycorrhizal fungi were identified by internal transcribed spacer rDNA
      sequencing and host species were verified with chloroplast trnL sequencing. To
      test whether Dicymbe and Aldina represent independent gains of the ECM symbiosis,
      we constructed a Fabaceae phylogeny using MatK and trnL. We identified four
      independent ECM lineages within the Fabaceae. * We detected a diverse community
      of 118 ECM species dominated by the /clavulina, /russula-lactarius, /boletus, and
      /tomentella-thelephora lineages. Ectomycorrhizal species in Agaricales,
      Atheliales and Polyporales may represent previously unrecognized tropical-endemic
      ECM lineages. Previous studies suggested that ECM fungi did not diversify in the
      tropics, but the /clavulina lineage appears to have a center of diversity in
      tropical South America. * Dicymbe and Aldina represent independent gains of the
      ECM symbiosis in Fabaceae but their fungal symbionts showed no host preferences.
      Spatial factors are more important than hosts in structuring the ECM fungal
      community in this ecosystem.

PMID- 21883232
TI  - New Rice for Africa (NERICA) cultivars exhibit different levels of post
      attachment resistance against the parasitic weeds Striga hermonthica and Striga
      asiatica.
AB  - Striga hermonthica and S. asiatica are root parasitic weeds that infect the major
      cereal crops of sub-Saharan Africa causing severe losses in yield. The
      interspecific upland NEw RICe for Africa (NERICA) cultivars are popular amongst
      subsistence farmers, but little is known about their post-attachment resistance
      against Striga. Here, we evaluate the post-attachment resistance levels of the
      NERICA cultivars and their parents against ecotypes of S. hermonthica and
      S.asiatica, characterize the phenotype of the resistance mechanisms and determine
      the effect of Striga on host biomass. Some NERICA cultivars showed good broad
      spectrum resistance against several Striga ecotypes, whereas others showed
      intermediate resistance or were very susceptible. The phenotype of a resistant
      interaction was often characterized by an inability of the parasite to penetrate
      the endodermis. Moreover, some parasites formed only a few connections to the
      host xylem, grew slowly and remained small. The most resistant NERICA cultivars
      were least damaged by Striga, although even a small number of parasites caused a
      reduction in above-ground host biomass. The elucidation of the molecular genetic
      basis of the resistance mechanisms and tolerance would allow the development of
      cultivars with multiple, durable resistance for use in farmers' fields.

PMID- 21883233
TI  - Pre-attachment Striga hermonthica resistance of New Rice for Africa (NERICA)
      cultivars based on low strigolactone production.
AB  - Striga hermonthica (Striga) is an obligate hemiparasitic weed, causing severe
      yield losses in cereals, including rice, throughout sub-Saharan Africa. Striga
      germination depends on strigolactones (germination stimulants) exuded by the host
      roots. The interspecific New Rice for Africa (NERICA) cultivars offer a
      potentially interesting gene pool for a screen for low germination-inducing rice
      cultivars. Exudates were collected from all NERICA cultivars and their parents
      (Oryza sativa and Oryza glaberrima) for the analysis of strigolactones. In vitro
      and in situ Striga germination, attachment and emergence rates were recorded for
      each cultivar. NERICA 1 and CG14 produced significantly less strigolactones and
      showed less Striga infection than the other cultivars. NERICAs 7, 8, 11 and 14
      produced the largest amounts of strigolactones and showed the most severe Striga
      infection. Across all the cultivars and parents, there was a positive
      relationship between the amount of strigolactones in the exudate and Striga
      germination, attachment and emergence rates. This study shows that there is
      genetic variation in Striga pre-attachment resistance in NERICA rice. Cultivars
      combining this pre-attachment resistance with post-attachment resistance (already
      identified) can provide a key component for durable integrated management of this
      noxious weed in cereal production systems in sub-Saharan Africa.

PMID- 21883234
TI  - Disruption of the ceramide synthase LOH1 causes spontaneous cell death in
      Arabidopsis thaliana.
AB  - The bioactive lipid ceramide is produced by the enzyme ceramide synthase, which
      exists in several isoforms in most eukaryotic organisms. Here, we investigated
      functional differences between the three ceramide synthase isoforms in
      Arabidopsis thaliana. The biochemical properties of the three ceramide synthases
      were investigated by comparing lipid profiles of yeast strains expressing LOH1,
      LOH2 or LOH3 with those of wild-type and loh1, loh2 and loh3 knockout plants.
      Expression profiles of the ceramide synthases and of the pathogenesis-related
      gene PR-1 were investigated by real-time PCR. Each ceramide synthase isoform
      showed a characteristic preference regarding acyl-CoA chain length as well as
      sphingoid base hydroxylation, which matches the pattern of ceramide and
      glucosylceramide species found in leaves. After extended culture under short-day
      conditions, loh1 plants showed spontaneous cell death accompanied by enhanced
      expression of PR-1. The levels of free trihydroxy sphingoid bases as well as
      ceramide and glucosylceramide species with C(16) fatty acid were significantly
      elevated while species with C(20) -C(28) fatty acids were reduced. These data
      suggest that spontaneous cell death in the loh1 line is triggered either by the
      accumulation of free trihydroxy sphingoid bases or ceramide species with C(16)
      fatty acid.

PMID- 21883235
TI  - Direction and extent of organelle DNA introgression between two spruce species in
      the Qinghai-Tibetan Plateau.
AB  - A recent model has shown that, during range expansion of one species in a
      territory already occupied by a related species, introgression should take place
      preferentially from the resident species towards the invading species and genome
      components experiencing low rates of gene flow should introgress more readily
      than those experiencing high rates of gene flow. Here, we use molecular markers
      from two organelle genomes with contrasted rates of gene flow to test these
      predictions by examining genetic exchanges between two morphologically distinct
      spruce Picea species growing in the Qinghai-Tibetan Plateau. The haplotypes from
      both mitochondrial (mt) DNA and chloroplast (cp) DNA cluster into two distinct
      lineages that differentiate allopatric populations of the two species. By
      contrast, in sympatry, the species share the same haplotypes, suggesting
      interspecific genetic exchanges. As predicted by the neutral model, all sympatric
      populations of the expanding species had received their maternally inherited
      mtDNA from the resident species, whereas for paternally inherited cpDNA
      introgression is more limited and not strictly unidirectional. Our results
      underscore cryptic introgressions of organelle DNAs in plants and the importance
      of considering rates of gene flow and range shifts to predict direction and
      extent of interspecific genetic exchanges.

PMID- 21883236
TI  - Molecular features of secondary vascular tissue regeneration after bark girdling
      in Populus.
AB  - Regeneration is a common strategy for plants to repair damage to their tissue
      after attacks from other organisms or physical assaults. However, how
      differentiating cells acquire regenerative competence and rebuild the pattern of
      new tissues remains largely unknown. Using anatomical observation and microarray
      analysis, we investigated the morphological process and molecular features of
      secondary vascular tissue regeneration after bark girdling in trees. After bark
      girdling, new phloem and cambium regenerate from differentiating xylem cells and
      rebuild secondary vascular tissue pattern within 1 month. Differentiating xylem
      cells acquire regenerative competence through epigenetic regulation and cell
      cycle re-entry. The xylem developmental program was blocked, whereas the phloem
      or cambium program was activated, resulting in the secondary vascular tissue
      pattern re-establishment. Phytohormones play important roles in vascular tissue
      regeneration. We propose a model describing the molecular features of secondary
      vascular tissue regeneration after bark girdling in trees. It provides
      information for understanding mechanisms of tissue regeneration and pattern
      formation of the secondary vascular tissues in plants.

PMID- 21883237
TI  - PpASCL, a moss ortholog of anther-specific chalcone synthase-like enzymes, is a
      hydroxyalkylpyrone synthase involved in an evolutionarily conserved sporopollenin
      biosynthesis pathway.
AB  - Sporopollenin is the main constituent of the exine layer of spore and pollen
      walls. Recently, several Arabidopsis genes, including polyketide synthase A
      (PKSA), which encodes an anther-specific chalcone synthase-like enzyme (ASCL),
      have been shown to be involved in sporopollenin biosynthesis. The genome of the
      moss Physcomitrella patens contains putative orthologs of the Arabidopsis
      sporopollenin biosynthesis genes. We analyzed available P.patens expressed
      sequence tag (EST) data for putative moss orthologs of the Arabidopsis genes of
      sporopollenin biosynthesis and studied the enzymatic properties and reaction
      mechanism of recombinant PpASCL, the P.patens ortholog of Arabidopsis PKSA. We
      also generated structure models of PpASCL and Arabidopsis PKSA to study their
      substrate specificity. Physcomitrella patens orthologs of Arabidopsis genes for
      sporopollenin biosynthesis were found to be expressed in the sporophyte
      generation. Similarly to Arabidopsis PKSA, PpASCL condenses hydroxy fatty acyl
      CoA esters with malonyl-CoA and produces hydroxyalkyl alpha-pyrones that probably
      serve as building blocks of sporopollenin. The ASCL-specific set of Gly-Gly-Ala
      residues predicted by the models to be located at the floor of the putative
      active site is proposed to serve as the opening of an acyl-binding tunnel in
      ASCL. These results suggest that ASCL functions together with other sporophyte
      specific enzymes to provide polyhydroxylated precursors of sporopollenin in a
      pathway common to land plants.

PMID- 21883238
TI  - One hundred important questions facing plant science research.

PMID- 21883239
TI  - Phylogeographically concordant chloroplast DNA divergence in sympatric Nothofagus
      s.s. How deep can it be?
AB  - * Here, we performed phylogenetic analyses and estimated the divergence times on
      mostly sympatric populations of five species within subgenus Nothofagus. We aimed
      to investigate whether phylogenetic relationships by nuclear internal transcribed
      spacer (ITS) and phylogeographic patterns by chloroplast DNA (cpDNA) mirror an
      ancient evolutionary history that was not erased by glacial eras. Extant species
      are restricted to Patagonia and share a pollen type that was formerly widespread
      in all southern land masses. Weak reproductive barriers exist among them. *
      Fifteen cpDNA haplotypes resulted from the analysis of three noncoding regions on
      330 individuals with a total alignment of 1794 bp. Nuclear ITS data consisted of
      822 bp. We found a deep cpDNA divergence dated 32 Ma at mid-latitudes of
      Patagonia that predates the phylogenetic divergence of extant taxa. Other more
      recent breaks by cpDNA occurred towards the north. * Complex paleogeographic
      features explain the genetic discontinuities. Long-lasting paleobasins and marine
      ingressions have impeded transoceanic dispersal during range expansion towards
      lower latitudes under cooler trends since the Oligocene. * Cycles of
      hybridization-introgression among extant and extinct taxa have resulted in
      widespread chloroplast capture events. Our data suggest that Nothofagus
      biogeography will be resolved only if thorough phylogeographic analyses and
      molecular dating methods are applied using distinct genetic markers.

PMID- 21883241
TI  - Light-activated antibacterial surfaces comprise photosensitizers.
AB  - Antibacterial surfaces were prepared using a base polyethylene sheet topped with
      a layer containing a mixed powder of poly (vinylidene fluoride) and
      photosensitizers (PSs). A crimpled stamp was placed on the mixed powder, and then
      it was passed through a heating and pressing device. The three chosen PSs were
      rose bengal, toluidine blue O and methylene blue. Scanning electron microscope
      analysis showed that the PS surface texture was coarse and highly developed.
      Measurement of the apparent contact angles of the droplets deposited on the PS
      surfaces using goniometry showed that all three surfaces were hydrophobic.
      Photodynamic analysis of the surfaces into which the PSs were incorporated
      indicated significant reactive oxygen species formation after illumination with
      light fluency rate of 1.46 mW cm(-2) for 30 min. Photodynamic inactivation assays
      performed in nutrient broth demonstrated more than 4 log reduction of the
      attached Escherichia coli after illumination (1.46 mW cm(-2)) for 24 h when the
      inoculum was 10(3) CFU mL(-1). However, more than 4 log reduction of
      Staphylococcus aureus occurred even when the cultures were illuminated for only 6
      h. Our results provide an inexpensive, simple, state-of-the-art method for
      preparing antibacterial surfaces that may help prevent infections in hospital
      surroundings and in some medical devices.

PMID- 21883242
TI  - Alleviation of adverse effects of drought stress on growth and some potential
      physiological attributes in maize (Zea mays L.) by seed electromagnetic
      treatment.
AB  - Effects of varying preseed magnetic treatments on growth, chlorophyll pigments,
      photosynthesis, water relation attributes, fluorescence and levels of
      osmoprotectants in maize plants were tested under normal and drought stress
      conditions. Seeds of two maize cultivars were treated with different (T0 [0 mT],
      T1 [100 mT for 5 min], T2 [100 mT for 10 min], T3 [150 mT for 5 min] and T4 [150
      mT for 10 min]) electromagnetic treatments. Drought stress considerably
      suppressed growth, chlorophyll a and b pigments, leaf water potential,
      photosynthetic rate (A), stomatal conductance (g(s)) and substomatal CO(2)
      concentration (C(i)), while it increased leaf glycinebetaine and proline
      accumulation in both maize cultivars. However, pretreated seeds with different
      magnetic treatments significantly alleviated the drought-induced adverse effects
      on growth by improving chlorophyll a, A, E, g(s), C(i) and photochemical
      quenching and nonphotochemical quenching, while it had no significant effect on
      other attributes. However, different magnetic treatments negatively affected the
      g(s) and C(i) particularly in cv. Agaiti-2002 under drought stress conditions. Of
      all magnetic treatments, 100 and 150 mT for 10 min were most effective in
      alleviating the drought-induced adverse effects. Overall, preseed electromagnetic
      treatments could be used to minimize the drought-induced adverse effects on
      different crop plants.

PMID- 21883243
TI  - Effect of laser dose and treatment schedule on excision wound healing in diabetic
      mice.
AB  - The present study was undertaken to evaluate a He-Ne laser (632.8 nm; 7 mW; 4.02
      mW cm(-2); 15 mm spot size) dose and the treatment schedule on diabetic wound
      healing in a mouse model. Circular wounds of 15 mm diameter were created on
      streptozotocin induced diabetic Swiss albino mice, and were uniformly illuminated
      with the single exposure of various He-Ne laser doses of 1, 2, 3, 4 and 5 J cm(
      2) respectively. Further, the treatment schedule was also optimized by exposing
      the wounds with 3 J cm(-2) at 0, 24 h, 48 h postwounding. Contraction kinetics,
      mean area under the curve and the mean healing time of the wounds were computed
      along with the collagen and the glucosamine levels in the wound ground tissues at
      various postwounding treatment schedules. Results of this study indicated that
      the single exposure of 3 J cm(-2) laser dose applied immediately after the
      wounding caused a significant reduction in the mean area under the curve and the
      mean healing time along with the elevated levels of collagen and glucosamine
      contents in the tissue compared to the controls. In conclusion, He-Ne laser dose
      of 3 J cm(-2) applied immediately after the wounding has demonstrated optimum
      wound healing compared to the other doses and treatment schedules.

PMID- 21883245
TI  - Photosensitization reactions in vitro and in vivo.
AB  - This review of Photochemistry and Photobiology summarizes articles published in
      2010, and highlights progress in the area of photosensitization. The synthesis of
      conjugated photosensitizers is an area of interest where increasing water
      solubility has been a goal. Targeting infrared sensitizer absorption has been
      another goal, and relates to the practical need of deep tissue absorption of
      light. Photodynamic techniques for inactivating microbes and destroying tumors
      have been particularly successful. Biologically, singlet oxygen
      [(1)O(2)((1)Delta(g))] is an integral species in many of these reactions,
      although photosensitized oxidations tuned to electron and hydrogen transfer (Type
      I) give rise to other reactive species, such as superoxide and hydrogen peroxide.
      How photoprotection against yellowing, oxygenation and degradation occurs was
      also an area of topical interest.

PMID- 21883244
TI  - Cell-type selective phototoxicity achieved with chlorophyll-a derived
      photosensitizers in a co-culture system of primary human tumor and normal lung
      cells.
AB  - The ATP-dependent transporter ABCG2 exports certain photosensitizers (PS) from
      cells, implying that the enhanced expression of ABCG2 by cancer cells may confer
      resistance to photodynamic therapy (PDT) mediated by those PS. In 35 patient
      derived primary cultures of lung epithelial and stromal cells, PS with different
      subcellular localization and affinity for ABCG2 displayed cell-type specific
      retention both independent and dependent on ABCG2. In the majority of cases, the
      ABCG2 substrate 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH) was lost
      from fibroblastic cells more rapidly than from their epithelial counterparts,
      even in the absence of detectable ABCG2 expression, facilitating selective
      eradication by PDT of epithelial over fibroblastic cells in tumor/stroma co
      cultures. Pairwise comparison of normal and transformed epithelial cells also
      identified tumor cells with elevated or reduced retention of HPPH, depending on
      ABCG2. Enhanced ABCG2 expression led to the selective PDT survival of tumor cells
      in tumor/stroma co-cultures. This survival pattern was reversible through HPPH
      derivatives that are not ABCG2 substrates or the ABCG2 inhibitor imatinib
      mesylate. PS retention, not differences in subcellular distribution or cell
      signaling responses, was determining cell type selective death by PDT. These data
      suggest that up-front knowledge of tumor characteristics, specifically ABCG2
      status, could be helpful in individualized PDT treatment design.

PMID- 21883246
TI  - Photooxidation of alkaloids: considerable quantum yield enhancement by rose
      bengal-sensitized singlet molecular oxygen generation.
AB  - The photooxidation of sanguinarine, coralyne and berberine was studied in
      oxygenated alkaline methanol solutions. Rose bengal as photosensitizer
      significantly accelerates the process, indicating the importance of singlet
      molecular oxygen in the reaction mechanism. The quantum yield of sensitized
      oxidation was found to increase significantly with pH and reaches 0.4 for
      berberine at pH 13.8. The direct oxidation of alkaloids is less efficient, the
      quantum yield does not exceed 0.01 even in oxygen-saturated solutions. The
      photoinduced electron ejection does not play a role in the oxidation. The
      uncharged pseudobase forms, which are present in alkaline medium, are oxidized
      much more easily than the alkaloid cations.

PMID- 21883247
TI  - gammaH2Ax: biomarker of damage or functional participant in DNA repair "all that
      glitters is not gold!".
AB  - The phosphorylation of H2Ax on its S139 site, gammaH2Ax, is important for the
      assembly of repair complexes at DNA double strand breaks (DSBs). The formation
      and functional role of gammaH2Ax after other kinds of DNA damage, especially UV
      light, where DSBs are rare, is less clear. Following UV light in the UVB and UVC
      ranges, complex distributions of gammaH2Ax can be identified, quite unlike the
      discrete enumerable foci seen after ionizing radiation. Several distinct
      distributions of gammaH2Ax occur: a low level nuclear-wide distribution of
      gammaH2Ax occurs during nucleotide excision repair; irregular focal distributions
      occur at arrested replication forks; high intensity nuclear-wide gammaH2Ax occurs
      in association with S-phase apoptosis. The intensity and distributions of
      gammaH2Ax vary according to the activity of excision repair, bypass polymerase
      and apoptotic caspases. The frequency of DSBs at arrested replication forks is
      low but highly variable in different cell types, and probably caused by enzymatic
      action. Despite the prominence of S139 phosphorylation following UV damage,
      mutation of this site has no influence on the UV damage response indicating that
      gammaH2Ax is a biomarker but not a participant in the UV-DNA damage response.

PMID- 21883248
TI  - Enhancing the scopolamine production in transgenic plants of Atropa belladonna by
      overexpressing pmt and h6h genes.
AB  - Atropa belladonna is officially deemed as the commercial plant to produce
      scopolamine in China. In this study we report the simultaneous overexpression of
      two functional genes involved in biosynthesis of scopolamine, which encode the
      upstream key enzyme putrescine N-methyltransferase (PMT) and the downstream key
      enzyme hyoscyamine 6beta-hydroxylase (H6H), respectively, in transgenic herbal
      plants Atropa belladonna. Analysis of gene expression profile indicated that both
      pmt and h6h were expressed at a higher level in transgenic lines, which would be
      favorable for biosynthesis of scopolamine. High-performance liquid chromatography
      result suggested that transgenic lines could produce higher accumulation of
      scopolamine at different levels compared with wild-type lines. Scopolamine
      content increased to 7.3-fold in transgenic line D9 compared with control lines.
      This study not only confirms that co-overexpression of pmt and h6h is an ideal
      method to improve the biosynthetic capacity of scopolamine but also successfully
      cultivates the transgenic line D9, which significantly enhanced the scopolamine
      accumulation. Our research can serve as an alternative choice to provide
      scopolamine resources for relative industry, which is more competitive than
      conventional market.

PMID- 21883249
TI  - gamma-Tocopherol methyltransferase from the green alga Chlamydomonas reinhardtii:
      functional characterization and expression analysis.
AB  - gamma-Tocopherol methyltransferase (gamma-TMT) (EC 2.1.1.95) is a very important
      enzyme in tocopherol biosynthesis in all photosynthetic organisms. In this paper,
      we present the functional characterization and expression analysis of gamma-TMT
      from the unicellular green alga Chlamydomonas reinhardtii. Recombinant TMT1
      enzyme was purified and characterized. The size of TMT1 subunit was estimated as
      37 kDa by sodium dodecylsulphate polyacrylamide gel electrophoresis (SDS-PAGE),
      in accordance with the predicted molecular size after TMT1 cDNA sequence.
      Recombinant TMT1 also showed an apparent molecular mass of 37 kDa in its native
      conformation, suggesting that native TMT1 has a monomeric structure similar to
      the plant TMTs already characterized. pH and temperature dependence of TMT1
      activity were also similar to plant TMTs. Substrate specificity studies showed
      that Chlamydomonas TMT1 is responsible for the conversion of gamma- and delta
      tocopherol to alpha- and beta-tocopherol, respectively. The kinetic properties of
      Chlamydomonas recombinant gamma-TMT activity were studied and gamma-TMT1 has a
      similar affinity for gamma- and delta-tocopherol. Promoter sequence analysis and
      expression analysis by northern blot revealed that tmt1 expression is strongly
      upregulated by high light and downregulated by low temperature. This regulatory
      pattern of tmt1 expression supports the idea that gamma- and alpha-tocopherol
      play specific roles in the adaptation to growth under low temperature and high
      light stress conditions.

PMID- 21883250
TI  - Exophiala sp. LHL08 reprograms Cucumis sativus to higher growth under abiotic
      stresses.
AB  - Endophytic fungi are potential sources of secondary metabolites; however, they
      are little known for phytohormones secretion and amelioration of plant growth
      under abiotic stresses. We isolated a novel endophyte from the roots of Cucumis
      sativus and identified it as a strain of Exophiala sp. by sequencing internal
      transcribed spacer/large subunit rDNA and phylogenetic analysis. Prior to
      identification, culture filtrate (CF) of Exophiala sp. has shown significant
      growth promotion of Waito-C [a gibberellins (GAs)-deficient mutant cultivar] and
      Dongjin-byeo (normal GAs biosynthesis cultivar) rice seedlings. CF analysis of
      Exophiala sp. showed the presence of physiologically active GAs (GA1, GA3, GA4
      and GA7) and inactive GAs (GA5, GA8, GA9, GA12 and GA20). Exophiala sp. had
      higher GAs in its CF than wild-type strain of Gibberella fujikuroi except GA3.
      Influence of Exophiala sp. was assessed on cucumber plant's growth and endogenous
      abscisic acid (ABA), salicylic acid (SA) and bioactive GAs under salinity and
      drought stresses. Exophiala sp.-treated plants have shown significantly higher
      growth and rescued the host plants from stress promulgated water deficit, osmotic
      and cellular damage. The altered levels of stress-responsive ABA showed low level
      of stress confined to endophyte-applied plants than control. Elevated levels of
      SA and bioactive GAs (GA3 and GA4) in endophyte-associated plants suggest stress
      modulating response toward salinity and drought. In conclusion, symbiotic
      relations between Exophiala and cucumber have reprogrammed the host plant growth
      under abiotic stresses, thus indicating a possible threshold role of endophytic
      fungi in stress alleviation. This study could be extended for improving
      agricultural productivity under extreme environmental conditions.

PMID- 21883251
TI  - Involvement of the abscisic acid catabolic gene CYP707A2 in the glucose-induced
      delay in seed germination and post-germination growth of Arabidopsis.
AB  - Earlier studies showed that sugars as signaling molecules play pivotal roles in
      the regulation of seed germination. ABA biosynthesis upregulation is suggested as
      one of the possible mechanisms mediating the glucose-induced delay in seed
      germination. In this study, the role of ABA catabolism in glucose-induced
      inhibition was investigated. Using Arabidopsis thaliana seeds, the results show
      that the repression of ABA catabolism by diniconazole aggravated the glucose
      induced delay in seed germination. The transcript and protein profiles of
      CYP707A2, a key gene encoding ABA 8'-hydroxylase in ABA catabolism in
      Arabidopsis, were significantly decreased by exogenous glucose treatment.
      Transgenic experiments confirmed that the over-expression of the CYP707A2 gene
      alleviated the glucose-induced inhibition effect, whereas the cyp707a2 mutant
      seeds displayed a hypersensitivity to glucose during imbibition. Exogenous
      glucose also arrested the early seedling development of Arabidopsis. The CYP707A2
      over-expression seedlings exhibited lower ABA levels and seemed less sensitive to
      exogenous glucose compared with wild type seedlings. In summary, the glucose
      induced delay in seed germination and seedling development is directly related to
      the suppression of ABA catabolism through the repression of the CYP707A2
      expression.

PMID- 21883252
TI  - Temporal variation in epidermal flavonoids due to altered solar UV radiation is
      moderated by the leaf position in Betula pendula.
AB  - The physiological mechanisms controlling plant responses to dynamic changes in
      ambient solar ultraviolet (UV) radiation are not fully understood: this
      information is important to further comprehend plant adaptation to their natural
      habitats. We used the fluorimeter Dualex to estimate in vivo the epidermal
      flavonoid contents by measuring epidermal UV absorbance (A(375) ) in Betula
      pendula Roth (silver birch) leaves of different ages under altered UV. Seedlings
      were grown in a greenhouse for 15 days without UV and transferred outdoors under
      three UV treatments (UV-0, UV-A and UV-A+B) created by three types of plastic
      film. After 7 and 13 days, Dualex measurements were taken at adaxial and abaxial
      epidermis of the first three leaves (L1, L2 and L3) of the seedlings. After 14
      days, some of the seedlings were reciprocally swapped amongst the treatments to
      study the accumulation of epidermal flavonoids in the youngest unfolded leaves
      (L3) during leaf expansion under changing solar UV environments. A(375)  of the
      leaves responded differently to the UV treatment depending on their position. UV
      B increased the A(375)  in the leaves independently of leaf position. L3 quickly
      adjusted A(375)  in their epidermis according to the UV they received and these
      adjustments were affected by previous UV exposure. The initial absence of UV-A+B
      or UV-A, followed by exposure to UV-A+B, particularly enhanced leaf A(375) .
      Silver birch leaves modulate their protective pigments in response to changes in
      the UV environment during their expansion, and their previous UV exposure history
      affects the epidermal-absorbance achieved during later UV exposure.

PMID- 21883253
TI  - Characterization of upregulated genes associated with high phosphorus
      accumulation in cucumber.
AB  - Excessive application of phosphorus (P)-rich manures to agricultural lands often
      results in P-accumulation in soils leading to water pollution through runoffs and
      leaching. Use of suitable plant species that can extract and sequester excess P
      from soil into their biomass is an effective method of remediation of P
      contaminated soils. Knowledge on the molecular responses of plants to high P
      accumulation and tolerance is lacking. Therefore, a suppression subtractive
      hybridization (SSH) strategy was employed to identify and elucidate the pattern
      of gene expression related to P-tolerance and accumulation in cucumber (Cucumis
      sativus L.), a P-accumulator plant. RNA isolated from cucumber grown in high P
      was used for 'tester' cDNA synthesis and SSH library preparation. A total of 63
      cDNAs were identified as showing upregulated expression in this plant in response
      to high P. No putative function could be assigned to 7 (11%) of the 63
      upregulated high P-modulated genes and 11 expressed sequence tags (ESTs) (17%)
      did not match database entries. The remaining 45 ESTs were grouped into five
      functional classes. The majority of these ESTs belonged to three groups:
      'metabolism', 'protein synthesis/degradation and signaling' and 'cell
      structure/cell wall'. Only six 'stress/defense'-related ESTs were identified from
      this library. The results of reverse northern blot analysis was further confirmed
      and validated through semi-quantitative RT-PCR carried out with representative
      ESTs identified in this study. The research reported here may contribute to a
      preliminary understanding of the high P-related gene expression in this P
      accumulating plant.

PMID- 21883254
TI  - The effects of phenotypic plasticity on photosynthetic performance in winter rye,
      winter wheat and Brassica napus.
AB  - The contributions of phenotypic plasticity to photosynthetic performance in
      winter (cv Musketeer, cv Norstar) and spring (cv SR4A, cv Katepwa) rye (Secale
      cereale) and wheat (Triticum aestivum) cultivars grown at either 20 degrees C
      [non-acclimated (NA)] or 5 degrees C [cold acclimated (CA)] were assessed. The 22
      40% increase in light-saturated rates of CO2 assimilation in CA vs NA winter
      cereals were accounted for by phenotypic plasticity as indicated by the dwarf
      phenotype and increased specific leaf weight. However, phenotypic plasticity
      could not account for (1) the differential temperature sensitivity of CO2
      assimilation and photosynthetic electron transport, (2) the increased efficiency
      and light-saturated rates of photosynthetic electron transport or (3) the
      decreased light sensitivity of excitation pressure and non-photochemical
      quenching between NA and NA winter cultivars. Cold acclimation decreased
      photosynthetic performance of spring relative to winter cultivars. However, the
      differences in photosynthetic performances between CA winter and spring cultivars
      were dependent upon the basis on which photosynthetic performance was expressed.
      Overexpression of BNCBF17 in Brassica napus generally decreased the low
      temperature sensitivity (Q10) of CO2 assimilation and photosynthetic electron
      transport even though the latter had not been exposed to low temperature.
      Photosynthetic performance in wild type compared to the BNCBF17-overexpressing
      transgenic B. napus indicated that CBFs/DREBs regulate not only freezing
      tolerance but also govern plant architecture, leaf anatomy and photosynthetic
      performance. The apparent positive and negative effects of cold acclimation on
      photosynthetic performance are discussed in terms of the apparent costs and
      benefits of phenotypic plasticity, winter survival and reproductive fitness.

PMID- 21883255
TI  - Mitochondrial alternative oxidase pathway protects plants against photoinhibition
      by alleviating inhibition of the repair of photodamaged PSII through preventing
      formation of reactive oxygen species in Rumex K-1 leaves.
AB  - The purpose of this study was to explore how the mitochondrial AOX (alternative
      oxidase) pathway alleviates photoinhibition in Rumex K-1 leaves. Inhibition of
      the AOX pathway decreased the initial activity of NADP-malate dehydrogenase (EC
      1.1.1.82, NADP-MDH) and the pool size of photosynthetic end electron acceptors,
      resulting in an over-reduction of the photosystem I (PSI) acceptor side. The over
      reduction of the PSI acceptor side further inhibited electron transport from the
      photosystem II (PSII) reaction centers to the PSII acceptor side as indicated by
      an increase in V(J)  (the relative variable fluorescence at J-step), causing an
      imbalance between photosynthetic light absorption and energy utilization per
      active reaction center (RC) under high light, which led to the over-excitation of
      the PSII reaction centers. The over-reduction of the PSI acceptor side and the
      over-excitation of the PSII reaction centers enhanced the accumulation of
      reactive oxygen species (ROS), which inhibited the repair of the photodamaged
      PSII. However, the inhibition of the AOX pathway did not change the level of
      photoinhibition under high light in the presence of the chloroplast D1 protein
      synthesis inhibitor chloramphenicol, indicating that the inhibition of the AOX
      pathway did not accelerate the photodamage to PSII directly. All these results
      suggest that the AOX pathway plays an important role in the protection of plants
      against photoinhibition by minimizing the inhibition of the repair of the
      photodamaged PSII through preventing the over-production of ROS.

PMID- 21883256
TI  - Evaluation of the Norwegian version of the Adolescent Stress Questionnaire (ASQ
      N): factorial validity across samples.
AB  - In spite of the potential significance of stressors, the past decades have
      yielded only limited and incremental progress in the field of the development of
      valid and reliable stress inventories for adolescents. The Adolescent Stress
      Questionnaire (ASQ-N) was developed to address the domain of stressors specific
      to adolescent experience. The present study reports an evaluation of factorial
      validity, as well as the construct validity of the Norwegian version of the
      Adolescent Stress Questionnaire (ASQ-N) across two samples, with the use of
      confirmatory factor analysis (CFA). Gender and age differences on the ASQ-N sub
      dimensions are also evaluated. The CFA supported a seven-factor structure, where
      all sub-dimensions showed adequate internal consistency. The sub-dimensions were
      correlated positively with measures of depression and anxiety, and were
      correlated negatively with self-esteem, supporting the construct validity of the
      ASQ-N. Significant gender differences in self-reported adolescent stress were
      found in five of the seven scales, where girls had higher mean scores than boys.
      The correlation between each stress scale and age was weak, with significant
      correlations found in four of the seven scales. It is suggested that the ASQ-N is
      a measure of adolescent stress that is adequate for the research context, as well
      as for clinical investigation.

PMID- 21883257
TI  - Are modern health worries associated with somatosensory amplification,
      environmental attribution style, and commitment to complementary and alternative
      medicine?
AB  - Relationship among modern health worries (MHWs), somatosensory amplification
      (SSA), and attributional styles was investigated in a cross-sectional
      questionnaire study. A total of 99 university students, 104 patients visiting
      their General Practitioners, and 102 future alternative therapists completed
      questionnaires assessing MHWs, SSA, negative affect (NA), and psychological,
      somatic and normalizing (environmental) attribution styles. Significant
      correlation between SSA and MHWs was found in all three samples. MHWs and
      psychological attribution style were significantly associated with Complementary
      and Alternative Medicine (CAM)-orientation in the regression equation even after
      controlling for SSA, NA, and sociodemographic variables. MHWs were independent
      from any attribution styles in the student and patient samples, while significant
      correlations with all three styles were found in the CAM group. Previously
      described association between MHWs and SSA was replicated in three different
      samples. The connection between MHWs and CAM preference seems to be independent
      from SSA, NA or any particular attribution style.

PMID- 21883258
TI  - Performances on Rey Auditory Verbal Learning Test and Rey Complex Figure Test in
      a healthy, elderly Danish sample--reference data and validity issues.
AB  - This study presents Danish data for Rey Auditory Verbal Learning Test (RAVLT) and
      Rey Complex Figure Test (RCFT) from 100 subjects aged 60-87 years. Education and
      estimated verbal intelligence (DART score) had a significant impact on the RAVLT
      trial 1-5 score but not on other RAVLT measures. The RCFT copy score was
      significantly related to age and the DART score. On RCFT recall a highly
      significant difference was found between persons who could make a faultless copy
      and persons with incomplete copy performance. Thus, this study presents separate
      data for RCFT recall scores according to the subjects' copying performance (in
      separate tables for age and education groups). For all measures on both RAVLT and
      RCFT wide distributions of scores were found and the impact of this broad score
      range on the tests' discriminative validity is discussed. RAVLT performances for
      elderly were similar to previous published meta-norms, but the included sample of
      elderly Danes performed better on RCFT (copy and recall) than elderly from the
      United States.

PMID- 21883259
TI  - The goal to be accepted by friends as underlying function of overt aggressive
      behaviour in immigrant adolescents.
AB  - This study investigated (1) to what extent the goal to be accepted by friends is
      an underlying function of overt aggressive behavior in adolescents, and (2)
      whether this function is more predictive than reactive aggression for overt
      aggressive behavior in first and second generation immigrants compared with
      natives. The sample comprised 339 native Austrians (51.6% girls), 126 first
      generation immigrants (48.4% girls), and 175 second generation immigrants (54.3%
      girls) aged 14 to 19 (M = 15.61). Data were collected via self-assessments.
      Multiple group latent means and covariance structures (MACS) models revealed that
      the goal to be accepted by friends was a stronger predictor than reactive
      aggression for overt aggressive behavior in first generation immigrants compared
      with second generation immigrants and natives. Furthermore, gender moderated
      these associations. The goal to be accepted by friends was a very strong
      predictor of overt aggressive behavior in first generation immigrant boys, but
      not in first generation immigrant girls. Results are discussed regarding the
      process of acculturation in first generation immigrant youth.

PMID- 21883260
TI  - British men's hair color preferences: an assessment of courtship solicitation and
      stimulus ratings.
AB  - Two studies examined the influence of women's hair color on approach behavior by
      British men and on ratings of physical attractiveness and personality. In Study
      1, a female confederate whose hair color was dyed blonde, brunette, or red was
      instructed to sit in several nightclubs. It was found that she was approached
      significantly more frequently by men in the blonde condition. In Study 2, images
      of the same confederate were rated by 126 men. Results showed that the brunette
      stimulus was rated as more physically attractive, intelligent, approachable,
      competent, and arrogant, whereas the blonde stimulus was rated as more needy.
      These results are discussed in relation to the literature on hair color and
      attractiveness, but also in terms of women's own perceptions of their hair color.

PMID- 21883261
TI  - Comprehensive analysis of RHD alleles in Argentineans with variant D phenotypes.
AB  - BACKGROUND: The serologic assignment of the RhD status may be hindered in
      patients with weak D expression. A comprehensive study of RHD alleles occurring
      in the mixed population of Argentina is necessary to evaluate the most suitable
      DNA typing strategy. STUDY DESIGN AND METHODS: A total of 18,379 patients from
      two stratified groups, Group 1 (G1; public hospital) and Group 2 (G2; private
      laboratory), were RhD phenotyped, and 88 samples with reduced D expression
      underwent molecular characterization. RESULTS: The frequencies of D+, D-, and
      variant D phenotypes differed significantly (p < 0.001) between G1 and G2 (94.49%
      vs. 87.66%, 5.15% vs. 11.58%, and 0.36% vs. 0.75%, respectively). Eleven alleles
      were responsible for the weak D expression. Approximately 60% of the variant D
      phenotypes from G1 and G2 were weak D Types 1 through 4.0/4.2 and 25% were DVII.
      RHD alleles associated with African ancestry were encountered in G1. A new 
      282G>A mutation within the promoter region of DAU-4 and DOL alleles was
      identified. Three weak D Type 1 samples on R(0) haplotypes were found in G1.
      CONCLUSIONS: The D phenotype distribution in G2 resembles that in Europeans while
      the frequencies in G1 account for the Amerindian and African genetic
      contribution. The genotyping strategy described here is suitable to study D
      variants in the overall population and could allow a better use of the few
      available D- units and a rational administration of anti-D immunoprophylaxis. The
      results also show that weak D Type 1 alleles do not exclusively segregate with a
      Ce allele, as assumed until present.

PMID- 21883262
TI  - Changes in coagulation factor activity and content of di(2-ethylhexyl)phthalate
      in frozen plasma units during refrigerated storage for up to five days after
      thawing.
AB  - BACKGROUND: Thawed plasma is typically transfused to supply coagulation factors
      but factor activity declines during refrigerated storage. Refrigerating thawed
      plasma for longer than 24 hours could reduce plasma wastage and make plasma more
      readily available for emergency transfusions. We measured coagulation factor
      activity and di(2-ethylhexyl)phthalate (DEHP) concentration in frozen plasma (FP)
      thawed and stored at 1 to 6 degrees C for up to 5 days. STUDY DESIGN AND METHODS:
      FP units prepared using "top-and-bottom" collection sets were thawed,
      refrigerated, and sampled aseptically at 0, 24, 72, and 120 hours after thawing
      (n = 54). Clotting factor activities and prothrombin times (PTs) were measured
      using an automated coagulation factor analyzer. DEHP was measured by high
      performance liquid chromatography after hexane extraction (n = 11). Unit
      sterility was confirmed using an automated microbial detection system. RESULTS:
      Factor (F)V and FVIII, but not FVII, declined significantly within 24 hours. By
      Day 5, mean losses were 20, 14, and 41%, in FV, FVII, and FVIII, respectively;
      fibrinogen activity did not change. PT values were prolonged by 9% on Day 5. Mean
      DEHP levels increased from 22 ppm at thaw to 66 ppm on Day 5. CONCLUSIONS: The
      bulk of coagulation factor activity losses during storage occurred in the first
      24 hours. Coagulation factor activities remaining in FP after 5 days did not
      differ from those previously reported in similar products frozen within 24 hours
      of phlebotomy. While DEHP levels in 5-day-thawed FP are not of concern for adult
      patients, for infants, DEHP levels can be minimized by using FP refrigerated for
      no more than 24 hours.

PMID- 21883263
TI  - Implication of transfected cell lines for the detection of alloantibodies against
      human neutrophil antigen-3.
AB  - BACKGROUND: Alloantibodies against human neutrophil antigen-3 (HNA-3) are
      responsible for the fatalities reported in transfusion-related acute lung injury.
      Consequently, reliable detection of these alloantibodies is mandatory to improve
      blood transfusion safety. In this study, we developed stable cell lines for the
      detection of HNA-3 antibodies. STUDY DESIGN AND METHODS: HEK293T were transfected
      with HNA-3a or HNA-3b constructs and sorted by flow cytometry according to high
      surface expression. Transfected cells were tested with sera containing HNA-3
      antibodies in flow cytometry and antibody capture assay (ACA). The results were
      compared with granulocyte agglutination test and granulocyte immunofluorescence
      test. RESULTS: In flow cytometry, 12 of 14 HNA-3a sera reacted specifically with
      HNA-3aa cells. One serum sample showed positive reaction with HNA-3bb cells. All
      HNA-3b sera recognized HNA-3bb cells. No reaction was observed with broad
      reactive antibodies against HLA Class I. In ACA, all HNA-3a sera (12/12) showed
      positive reactivity with HNA-3aa cells with no cross-reactivity with HNA-3bb
      cells. Again, all HNA-3b sera reacted with HNA-3bb cells only. Furthermore,
      genotyping of 249 individuals detected a new HNA-3 allele caused by a nucleotide
      substitution C>T at Position 457 leading to L(153)F mutation in choline
      transporter-like protein-2. This mutation impairs polymerase chain reaction with
      sequence-specific primers based HNA-3a typing. However, analysis with cells
      expressing F(153) isoform showed that this mutation did not alter the binding of
      HNA-3 antibodies. CONCLUSIONS: This study demonstrated that HEK293T cells
      expressing stable recombinant HNA-3 are suitable for the detection of HNA-3
      alloantibodies allowing reliable screening of blood products.

PMID- 21883264
TI  - Flow cytometry assessment of apoptotic CD34+ cells by annexin V labeling may
      improve prediction of cord blood potency for engraftment.
AB  - BACKGROUND: Nonviable CD34+ cells are commonly assessed by standard flow
      cytometry using the nuclear stain 7-aminoactinomycin D (7AAD). 7AAD, however,
      only detects necrotic and late apoptotic cells, not earlier apoptosis, which
      engraft poorly in animal models of cord blood (cord) transplantation. The
      standard method, therefore, may overestimate engraftment potency of cord units
      under certain conditions. STUDY DESIGN AND METHODS: To detect apoptotic events,
      costaining with 7AAD and annexin V (AnnV), in parallel with the quantitative,
      standard enumeration, was used. Cord units were assessed before and after
      cryopreservation using both staining methods and colony-forming units (CFU) to
      determine if graft potency can be predicted using a "functional flow cytometry"
      approach. RESULTS: Significant numbers of CD34+ AnnV+ events were found within
      the 7AAD-gated population. Nonapoptotic cell dose (CD34+ AnnV-) correlated well
      with CFUs in both a small-scale (n = 10) and a large-scale banking study (n =
      107). Finally, following samples postthaw with time showed increasing numbers of
      apoptotic CD34+ cells and consequently the AnnV assessed dose was better at
      predicting the CFU compared with just the standard enumeration. CONCLUSION:
      Defining the apoptotic population of CD34+ cells improved the prediction of CFU,
      making this method a rapid test of potency for assessment of cord units for
      clinical use.

PMID- 21883265
TI  - Detection of bacterial contamination in prestorage culture-negative apheresis
      platelets on day of issue with the Pan Genera Detection test.
AB  - BACKGROUND: Bacterial contamination is currently the most important infectious
      risk associated with transfusion of platelet (PLT) products. Prestorage culture
      has reduced but not eliminated this problem. STUDY DESIGN AND METHODS: Eighteen
      hospitals studied the Pan Genera Detection (PGD) test, a rapid, lateral-flow
      immunoassay for the detection of Gram-positive and Gram-negative bacteria. The
      PGD test was performed on day of issue on apheresis PLTs released by collection
      centers as culture negative. Confirmatory bacterial culture was performed when
      PGD tests were repeatedly reactive, with three sites performing culture on all
      doses studied. RESULTS: PGD tests on nine of 27,620 (1:3069, 95% confidence
      interval [CI] 1:6711 to 1:1617; or 326 per million, 95% CI 149-618 per million)
      apheresis PLT doses were repeatedly reactive and verified as bacterially
      contaminated by confirmatory culture. Bacterial species isolated included
      coagulase-negative staphylococci (n = 6), Bacillus sp. (n = 2), and Enterococcus
      faecalis (n = 1). The ages of these contaminated doses were Day 3 (n = 4), Day 4
      (n = 2), and Day 5 (n = 3). Two contaminated doses with nonreactive PGD tests
      were detected among 10,424 doses at hospitals where concurrent culture was
      performed, and one other was identified via a transfusion reaction investigation.
      There were 142 PGD false positives (0.51%). CONCLUSIONS: The PGD test detected
      bacterial contamination in 1:3069 (9 of 27,620) doses released as negative by
      prestorage culture in PLTs as young as 3 days old. Three contaminated doses, two
      clinically insignificant, had nonreactive PGD tests, while 0.51% of tests were
      false positives. Application of this test on day of issue can interdict
      contaminated units and prevent transfusion reactions.

PMID- 21883266
TI  - Long-term follow-up among Danish transfusion recipients identified in the
      national hepatitis C lookback.
AB  - BACKGROUND: In 1996, a national lookback study was performed in Denmark
      identifying 1018 patients exposed to hepatitis C virus (HCV) by transfusion
      before 1991. The objective of this study was to describe morbidity and mortality
      during extended follow-up among patients in the Danish HCV lookback cohort alive
      in 1996. STUDY DESIGN AND METHODS: In a retrospective cohort study of 230
      patients exposed to HCV by blood transfusion and alive in 1996 we extracted data
      from national registers and compared these with a matched group of unexposed
      transfusion recipients. RESULTS: Among 230 HCV-exposed recipients alive in 1996,
      124 (53.9%) had chronic hepatitis C, 43 (18.7%) were not infected, and 63 (27.4%)
      had incomplete HCV data. In 2009, 121 (52.6%) were still alive a median of 21.8
      years after transfusion. The mortality rate among the HCV-exposed recipients
      followed from 1996 was 4.9 per 100 person-years (PY). The incidence of liver
      cirrhosis and decompensated cirrhosis was 1.0 per 100 PY and 0.4 per 100 PY,
      respectively; 16.5% had cirrhosis at death. Among HCV-exposed recipients, no
      difference in all-cause or liver-related mortality was observed between HCV
      infected and HCV-uninfected recipients. Further, there was no difference in
      mortality between HCV-exposed and -unexposed transfusion recipients (mortality
      rate ratio [MRR], 1.06; 95% confidence interval [CI], 0.96-1.17; p = 0.47), but
      liver-related mortality was significantly higher among HCV-exposed patients (MRR,
      10.0; 95% CI, 7.20-17.7; p < 0.001). CONCLUSION: Two decades after exposure to
      blood products from HCV-infected donors, only 121(11.8%) of 1018 recipients
      remained alive. For HCV-exposed recipients no excess all-cause mortality was
      observed, but liver-related mortality was significantly increased.

PMID- 21883268
TI  - Bacterial screening of outdated buffy coat platelet pools using a culture system
      and a rapid immunoassay.
AB  - BACKGROUND: Canadian Blood Services performs bacterial screening of buffy coat
      platelet pools (BCPs) using aerobic BacT/ALERT cultures. This study aimed to
      determine the rate of detection failures during initial platelet (PLT) screening
      and evaluate the introduction of anaerobic cultures and immunoassay testing to
      assess the safety of extending PLT storage beyond 5 days. STUDY DESIGN AND
      METHODS: Outdated (7- to 10-day-old) BCPs that tested negative during initial
      screening were assayed with BacT/ALERT and the Verax PLT Pan Genera detection
      (PGD) test, an immunoassay that detects Gram-positive (GP) and Gram-negative (GN)
      bacteria. BacT/ALERT aerobic and anaerobic culture bottles were inoculated with 8
      to 10 mL of BCP and incubated for up to 6 days. The PGD test was performed
      following manufacturer's instructions. Positive results were confirmed using the
      BacT/ALERT and PGD tests, blood agar culture, and Gram staining. Invalid PGD
      results were investigated. RESULTS: A total of 4002 BCPs were tested with one
      (0.025%) true positive (Staphylococcus epidermidis) found by both the BacT/ALERT
      and the PGD assays. Fifty-four (1.35%) false-positive BacT/ALERT cultures were
      obtained mainly due to instrument errors involving anaerobic cultures. Eleven
      (0.27%) false-positive PGD tests were observed in the GP window of the strip.
      Forty-nine (1.2%) invalid PGD results were obtained mostly before implementation
      of a humidity chamber. CONCLUSION: Testing of outdated BCPs suggests that
      introducing anaerobic cultures would result in significant PLT wastage due to a
      high rate of false positives. Contaminated BCPs still escape detection during
      initial testing; therefore, extension of PLT storage may be possible if repeat
      screening is performed before transfusion.

PMID- 21883267
TI  - Allergic agonists in apheresis platelet products are associated with allergic
      transfusion reactions.
AB  - BACKGROUND: The mechanisms that underlie allergic transfusion reactions (ATRs)
      are not well characterized, but likely involve recipient, donor, and product
      factors. To assess product factors associated with ATRs, we investigated
      candidate mediators in apheresis platelet (PLT) products associated with ATRs and
      controls. STUDY DESIGN AND METHODS: Using bead-based and standard enzyme-linked
      immunosorbent assays, we tested supernatants from 20 consecutive apheresis PLT
      transfusions associated with ATRs and 30 control products for concentrations of
      mediators in three categories: acute inflammatory mediators, direct agonists of
      basophils and mast cells, and growth and/or priming factors of basophils and mast
      cells. RESULTS: Median concentrations of the direct allergic agonists C5a, brain
      derived neurotrophic factor (BDNF), and CCL5 (RANTES) were 16.6, 41.8, and 13.9%
      higher, respectively, in the supernatant of apheresis PLT products that were most
      strongly associated with ATRs (p < 0.05 for each mediator). Other direct agonists
      (macrophage inflammatory protein-1alpha, monocyte chemotactic protein-1, eotaxin
      1, interleukin-8) were similar between groups. Concentrations of acute
      inflammatory mediators and basophil growth and/or priming factors were also
      similar between groups (p > 0.2 for all associations). CONCLUSION: The allergic
      agonists C5a, BDNF, and CCL5 may be mediators of ATRs in apheresis PLT products.
      Acute inflammatory proteins and basophil and/or mast cell growth and priming
      factors do not appear to be associated with apheresis PLT products that cause
      ATRs.

PMID- 21883269
TI  - Red blood cell transfusions and tissue oxygenation in anemic hematology
      outpatients.
AB  - BACKGROUND: There is little clinical evidence that red blood cell (RBC)
      transfusions improve oxygen availability at the microcirculatory level. We tested
      the hypotheses that anemia in chronically anemic patients with relatively healthy
      microcirculation would be associated with low tissue hemoglobin (Hb) and tissue
      oxygenation levels and that these conditions would be improved after RBC
      transfusions. STUDY DESIGN AND METHODS: Near-infrared spectroscopy (NIRS) was
      used to determine tissue oxygen saturation (StO(2)) and tissue Hb index (THI; an
      index of the amount of Hb in the NIRS measurement volume) in the thenar eminence
      and sublingual tissue before and 30 minutes after RBC transfusions in 20
      chronically anemic hematology outpatients. Data are presented as median (25%
      75%). RESULTS: The patients received three (two to three) bags of RBCs in saline
      adenine-glucose-mannitol with an age of 21 (7-21) days, which was infused
      intravenously at the rate of 0.7 bag/hr. RBC transfusions significantly increased
      hematocrit level from 26% (24%-28%) to 32% (30%-34%; p < 0.0001), Hb level from
      8.2 (7.6-8.9) g/dL to 11.0 (9.9-11.8) g/dL (p < 0.0001), whole blood viscosity
      from 3.4 (3.1-3.5) mPa/sec to 4.2 (4.0-4.5) mPa/sec (p < 0.0001), thenar StO(2)
      from 81% (80%-84%) to 86% (81%-89%; p = 0.002), thenar THI from 11.2 (9.3-13.3)
      AU to 13.7 (9.7-15.3) AU (p = 0.024), sublingual StO(2) from 86% (81%-89%) to 91%
      (86%-92%; p < 0.0001), and sublingual THI from 15.2 (13.0-17.4) AU to 17.2 (13.5
      19.7) AU (p = 0.040). CONCLUSION: Although anemia in chronically anemic
      hematology outpatients was not associated with low StO(2) and THI levels, RBC
      transfusions were successful in improving these variables.

PMID- 21883270
TI  - Effects of granulocyte-colony-stimulating factor on Monosomy 7 aneuploidy in
      healthy hematopoietic stem cell and granulocyte donors.
AB  - BACKGROUND: Reports of Monosomy 7 in patients receiving granulocyte-colony
      stimulating factor (G-CSF) have raised concerns that this cytokine may promote
      genomic instability. However, there are no studies addressing whether repeated
      administration of G-CSF produces Monosomy 7 aneuploidy in healthy donors. STUDY
      DESIGN AND METHODS: We examined Chromosomes 7 and 8 by fluorescent in situ
      hybridization (FISH) in CD34+ cells from 35 healthy hematopoietic stem cell
      transplant (HSCT) donors after G-CSF administration for 5 days and by spectral
      karyotyping analysis (SKY) in four individuals to assess chromosomal integrity.
      We also studied 38 granulocyte donors who received up to 42 doses of G-CSF and
      dexamethasone (Dex) using FISH for Chromosomes 7 and 8. RESULTS: We found no
      abnormalities in Chromosomes 7 and 8 in G-CSF-mobilized CD34+ cells when assessed
      by FISH or SKY, nor did we detect aneuploidy in G-CSF- and Dex-treated donors.
      CONCLUSION: G-CSF does not promote clinically detectable Monosomy 7 or Trisomy 8
      aneuploidy in HSCT or granulocyte donors. These findings should be reassuring to
      healthy HSCT and granulocyte donors.

PMID- 21883271
TI  - A standardized immunofluorescence test method with human neutrophil antigen
      expressing cell lines to enhance antibody detection.
AB  - There is an international need for a large-scale human neutrophils antigen (HNA)
      antibody screening platform to minimize the risk of antibody-mediated transfusion
      related acute lung injury. However, sourcing a substantial, reliable source of
      HNA, as well as the scarcity of well-characterized HNA antisera for validating
      new screening platforms, remain as major obstacles. This short communication
      presents an improved protocol for the effective use of HNA-expressing KY cells as
      a screening platform using eight well-characterized HNA antisera of a single
      defined specificity.

PMID- 21883272
TI  - Expression of the Rh/RhAG complex is reduced in Mi.III erythrocytes.
AB  - BACKGROUND AND OBJECTIVES: Miltenberger blood group antigen subtype III (Mi.III)
      is characterized by expression of a glycophorin B-A-B hybrid (Gp.Mur) on the
      erythrocyte surface. The two alleles of glycophorin B are substituted with the B
      A-B hybrid alleles in homozygous Mi.III (Mi.III(+/+)), and thus, Mi.III(+/+)
      erythrocytes lack glycophorin B (GPB) and express Gp.Mur only. Because GPB is a
      major component of the Rh complex on RBCs, in this study, we explored how the
      absence of GPB might affect Rh expression in Mi.III RBCs. MATERIALS AND METHODS:
      (1) Mi.III+ RBCs were serologically identified and further differentiated their
      homozygosity or heterozygosity by immunoblot or direct sequencing. (2) RhD and
      RhCcEe mRNA was cloned, and their sequences analysed. (3) The expression levels
      of Rh antigen, Rh-associated glycoprotein (RhAG) and the U antigen in MI.III vs.
      non-Mi.III RBCs were assessed by flow cytometry and Western blot. RESULTS:
      Compared with the non-Mi.III samples, the surface expression of the Rh antigen
      was reduced to 76.4% in Mi.III(+/+) RBCs and 93.6% in Mi.III(+/-). RhAG
      expression was also significantly reduced in Mi.III(+/+), but not in Mi.III(+/-).
      The U antigen expression in Mi.III(+/-) was only 14.9% relative to the control
      RBCs, while GPB was half the level of the controls. The mRNA sequences of Rh
      polypeptides from Mi.III+ samples were identical to the NCBI reference sequences.
      CONCLUSION: Substitution of GPB with Gp.Mur significantly reduced the expression
      of Rh antigen and RhAG on the Mi.III(+/+) erythrocyte membrane. The Mi.III
      phenotype is predicted to induce considerable structural variations within the
      band 3/Rh-associated macrocomplexes.

PMID- 21883273
TI  - Infectivity of pre-seroconversion donations: an analysis of lookback exercises in
      The Netherlands, 2000-2006.
AB  - BACKGROUND AND OBJECTIVES: Blood can be infectious if it is donated shortly
      before infection with hepatitis B virus (HBV), hepatitis C virus (HCV) or human
      immunodeficiency virus (HIV) becomes detectable. Lookback exercises may detect
      infection in recipients of pre-seroconversion donations. This study provides an
      analysis of the Dutch lookback exercises in the years 2000 through 2006.
      MATERIALS AND METHODS: All lookback procedures, triggered by 50 repeat donors
      seroconverting for HBV (n=32), HCV (n=3), HIV (n=14) and HBV + HIV (n=1), were
      analysed. Recipients and archived samples of the 96 implicated donations were
      tested. RESULTS: For 76 donations, a stored sample was available for HBV, HCV, or
      HIV PCR testing, revealing two HBV-DNA-positive pre-seroconversion donations.
      Ninety-three lookback procedures were initiated, to which 91 of 93 hospitals
      responded. In 87 of 91 cases, the implicated blood product had been administered.
      In 39 of 87 cases, the recipient was tested, revealing one HIV and two HBV
      infections. The HIV infection was considered pre-existent. The two HBV-positive
      patients received components from the donation of which the repository sample
      tested positive for HBV-DNA. Components of the second HBV-positive pre
      seroconversion donation had not been administered. CONCLUSION: Among 39
      recipients of pre-seroconversion donations, 2 (5%) were found HBV infected by
      transfusion. The labour-intensive lookback procedures did not reveal any
      conclusive transmissions additional to the infections detected by PCR testing of
      repository pre-seroconversion samples.

PMID- 21883274
TI  - Toward an interdisciplinary science of consumption.
AB  - Scientific perspectives on the drive to consume were presented in Ann Arbor,
      Michigan, at the conference entitled "The Interdisciplinary Science of
      Consumption: Mechanisms of Allocating Resources Across Disciplines." The meeting,
      which took place May 12-15, 2010 and was sponsored by Rackham Graduate School and
      the Department of Psychology at the University of Michigan, included
      presentations on human, primate, and rodent models and spanned multiple domains
      of consumption, including reward seeking, delay discounting, food-sharing
      reciprocity, and the consumption and display of material possessions across the
      life span.

PMID- 21883275
TI  - Combining H1-antihistamines and nasal corticosteroids to treat allergic rhinitis
      in general practice.

PMID- 21883276
TI  - Pulpitis as clinical presentation of photoallergic contact dermatitis due to
      chlorpromazine.

PMID- 21883277
TI  - PTGDR gene in asthma: a functional, genetic, and epigenetic study.
AB  - BACKGROUND: Asthma affects more than 300 million individuals in the world.
      Several studies have demonstrated the importance of the genetic component. The
      aim of this study is to develop a holistic approach, including genetic,
      epigenetic, and expression analysis to study the Prostaglandin D2 receptor gene
      (PTGDR) in asthmatic patients. METHODS: In this study, 637 Caucasian individuals
      were included. Genetic variants were characterized by sequencing, and haplotype
      and diplotype combinations were established. Electrophoretic mobility shift
      assays (EMSAs) were performed with different promoter variants. An epigenetic
      analysis of PTGDR was for the first time developed by MassArray assays, and gene
      expression was determined by real-time polymerase chain reaction. RESULTS: The 
      197T > C (Fisher's P = 0.028) and -613C > T (Fisher's P < 0.001) polymorphisms
      were found to be significantly associated with allergic asthma and allergy to
      pollen and mites, respectively. In addition, several haplotype and diplotype
      combinations were associated with different allergy and asthma phenotypes. The
      presence of the -613C > T SNP determined variations in the EMSAs. Moreover,
      consistent differences in the methylation and expression patterns were observed
      between asthmatic patients and controls determining a 2.34-fold increase of PTGDR
      gene expression in asthmatic patients. CONCLUSIONS: Genetic combinations
      described have functional implications in the PTGDR promoter activity by changing
      the transcription factors affinity that will help characterize different risk
      groups. The differences observed in the transcription factors affinity and in the
      methylation pattern bring insight into different transcription regulation in
      these patients. To the best of our knowledge, this is the first work in which the
      implication of genetic and epigenetic factors of PTGDR has been characterized
      pointing to putative therapeutic targets.

PMID- 21883278
TI  - Computationally predicted IgE epitopes of walnut allergens contribute to cross
      reactivity with peanuts.
AB  - BACKGROUND: Cross-reactivity between peanuts and tree nuts implies that similar
      immunoglobulin E (IgE) epitopes are present in their proteins. OBJECTIVE: To
      determine whether walnut sequences similar to known peanut IgE-binding sequences,
      according to the property distance (PD) scale implemented in the Structural
      Database of Allergenic Proteins, react with IgE from sera of patients with
      allergy to walnut and/or peanut. METHODS:   Patient sera were characterized by
      western blotting for IgE binding to nut protein extracts and to peptides from
      walnut and peanut allergens, similar to known peanut epitopes as defined by low
      PD values, synthesized on membranes. Competitive enzyme-linked immunosorbent
      assay (ELISA) was used to show that peanut and predicted walnut epitope sequences
      compete with purified Ara h 2 for binding to IgE in serum from a cross-reactive
      patient. RESULTS: Sequences from the vicilin walnut allergen Jug r 2, which had
      low PD values to epitopes of the peanut allergen Ara h 2, a 2S albumin, bound to
      IgE in sera from five patients who reacted to either walnut or peanut or both. A
      walnut epitope recognized by sera from six patients mapped to a surface-exposed
      region on a model of the N-terminal pro-region of Jug r 2. This predicted walnut
      epitope competed for IgE binding to Ara h 2 in serum as well as the known IgE
      epitope from Ara h 2. CONCLUSIONS: Sequences with low PD value (< 8.5) to known
      IgE epitopes could contribute to cross-reactivity between allergens. This further
      validates the PD scoring method for predicting cross-reactive epitopes in
      allergens.

PMID- 21883279
TI  - Changes in basophil activation during grass-pollen sublingual immunotherapy do
      not correlate with clinical efficacy.
AB  - BACKGROUND: Biomarkers predicting the safety and efficacy of sublingual
      immunotherapy (SLIT) remain to be established. METHODS: Eighty-nine patients with
      allergic rhinoconjunctivitis to grass pollen received either a placebo or five
      grass-pollen daily tablet sublingually for 4 months. Following exposure in an
      allergen challenge chamber, clinical responders and nonresponders were identified
      individually by evaluating their rhinoconjunctivitis total symptom score (RTSS).
      Activation of peripheral blood basophils was measured by cytofluorometry before
      and after 2 or 4 months of immunotherapy, based on CD203c surface expression
      following allergen stimulation. RESULTS: Patients receiving the grass-pollen
      tablet had a relative mean improvement of 29.3% vs placebo in the average RTSS
      after 4 months of SLIT (P < 0.0003). No significant changes in basophil
      activation were noticed after 2 or 4 months of SLIT despite induction of specific
      IgGs. Among individual clinical responders, basophil activation was either
      decreased, increased, or unmodified during SLIT. Levels of basophil activation
      prior to immunotherapy were not predictive of local adverse reactions associated
      with immunotherapy. A moderate association was found between basophil activation
      and allergen-specific IgE levels, skin reactivity, or RTSS, suggesting that the
      former is, to some extent, indicative of disease severity. As such, patients with
      the highest level of basophil activation before treatment were more likely to
      benefit clinically from SLIT. CONCLUSIONS: Allergen reactivity of peripheral
      blood basophils is not a biomarker for adverse events or early onset of clinical
      responses to SLIT.

PMID- 21883280
TI  - Clonal expansion of T cells in patients with eosinophilic lung disease.

PMID- 21883282
TI  - In vitro cultivation of shrimp Taura syndrome virus (TSV) in a C6/36 mosquito
      cell line.

PMID- 21883281
TI  - Risk factors for developing pain in normospermic patients with varicocoele.
AB  - To assess the possible risk factors for developing pain in normospermic adult
      varicocoele patients, 42 adult patients with left painful varicocoele (group 1)
      and 35 age-matched patients with left painless varicocoele (group 2) were
      recruited to this study. All the patients had normal semen quality (spermatozoa
      density, motility and morphology). Pain score on a 10-cm visual analogue scale
      was used to assess the scrotal pain as a result of varicocoele. The severity of
      pain was defined as follows: mild pain (1-3 cm), moderate pain (4-6 cm) and
      severe pain (7-10 cm). The parameters for comparison included body mass index
      (BMI), the distance from the renal hilum to scrotum (DRS), semen quality and pH
      value, serum concentration of follicle-stimulating hormone (FSH), luteinizing
      hormone (LH), prolactin, testosterone, alkaline phosphatase (Alk-p), lactate
      dehydrogenase (LDH), testicular volume and discrepancy (%), grade of varicocoele
      and peak retrograde flow (PRF) and spontaneous venous reflux (SVR) by colour
      Doppler ultrasound and scrotal temperature (ST). The mean ages were 27.8 and 27.1
      years old in groups 1 and 2, respectively. By multivariate analysis, patients in
      group 1 had significantly higher PRF, ST, DRS and rate of SVR, and lower BMI than
      those in group 2. Furthermore, there were significant differences in PRF, DRS and
      BMI among patients in group 1 with different degrees of pain. Conclusively,
      normospermic adult patients with left painful varicocoele had significantly
      higher peak retrograde flow, ST, distance from the renal hilum to scrotum, and
      rate of spontaneous venous reflux and lower BMI than those with left painless
      varicocoele. Furthermore, varicocoele patients with severe pain had significantly
      higher peak retrograde flow and distance from the renal hilum to scrotum, and
      lower BMI than those with moderate and mild pain.

PMID- 21883283
TI  - Expression pattern of heat-shock cognate 70 gene of humphead snapper, Lutjanus
      sanguineus (Cuvier), infected by Vibrio harveyi.
AB  - The heat-shock cognate 70 (HSC70) gene of humphead snapper, Lutjanus sanguineus,
      designated as ByHSC70, was cloned by rapid amplification of cDNA ends (RACE) with
      the primers designed from the known expressed sequence tag (EST) identified from
      the subtracted cDNA library of the head kidney of humphead snapper. The full
      length cDNA of ByHSC70 is 2313 bp, containing a 5' terminal untranslated region
      (UTR) of 96 bp, a 3' terminal UTR of 267 bp, and an open reading frame (ORF) of
      1950 bp encoding a polypeptide of 650 amino acids with a theoretical molecular
      weight of 71.21 kDa and an estimated isoelectric point (pI) of 5.08. ByHSC70
      contained three classical HSP70 family signatures. BLAST analysis showed that the
      amino acid sequence of ByHSC70 had the highest similarity of 99% when compared
      with other HSC70s. Fluorescent real-time quantitative RT-PCR was used to examine
      the expression of ByHSC70 gene in eight kinds of tissues/organs of humphead
      snapper after challenge with Vibrio harveyi. There was a clear time-dependent
      expression pattern of ByHSC70 in head kidney, spleen and thymus after bacterial
      challenge, and the expression of mRNA reached a maximum level at 9, 6 and 24 h
      post-infection and then returned to control levels after 15, 24 and 36 h,
      respectively. Our results suggest that HSC70 is an important component in the
      immune system of humphead snapper, its their rapid transcriptional upregulation
      in response to V. harveyi infection might be important for survival of humphead
      snapper.

PMID- 21883284
TI  - Pharmacokinetics of oral meloxicam in ruminant and preruminant calves.
AB  - The pharmacokinetics of oral meloxicam has been studied in ruminant, but not
      preruminant calves. Oral meloxicam was administered at 0.5 mg/kg to six ruminant
      calves via gavage (RG); to six preruminant calves via gavage (PRG); and to six
      preruminant calves via suckling in milk replacer (PRF). Plasma drug
      concentrations, determined over 120-h postadministration, were analyzed by
      compartmental and noncompartmental methods. The rate of drug absorption was
      faster (P<0.01) in PRF (0.237+/-0.0478/h) than RG calves (0.0815+/-0.0188/h),
      while absorption in PRG calves (0.153+/-0.128/h) was not different from other
      groups. C(max) was lower (P=0.03) in PRF (1.27+/-0.430 MUg/mL) than in PRG calves
      (2.20+/-0.467 MUg/mL), while C(max) of RG calves (1.95+/-0.955 MUg/mL) was not
      different from other groups. V/F was higher in PRF calves (365+/-57 mL/kg) than
      either PRG (177+/-63 mL/kg, P<0.01) or RG (232+/-83 mL/kg, P=0.01) calves. These
      observations were likely due to differences in bioavailability, physiological
      maturity, and timing of the drug delivery into different compartments of the
      ruminant gastrointestinal tract. Results suggest that an adjustment in meloxicam
      dose may be necessary when administered with milk replacer.

PMID- 21883285
TI  - Pharmacokinetics of tramadol and its major metabolites in alpacas following
      intravenous and oral administration.
AB  - Tramadol, a centrally acting opioid analgesic with monamine reuptake inhibition,
      was administered to six alpacas (43-71 kg) randomly assigned to two treatment
      groups, using an open, single-dose, two-period, randomized cross-over design at a
      dose of 3.4-4.4 mg/kg intravenously (i.v.) and, after a washout period, 11 mg/kg
      orally. Serum samples were collected and stored at -80 degrees C until assayed by
      HPLC. Pharmacokinetic parameters were calculated. The mean half-lives (t(1/2))
      i.v. were 0.85+/-0.463 and 0.520+/-0.256 h orally. The Cp(0) i.v. was 2467+/-540
      ng/mL, and the C(max) was 1202+/-1319 ng/mL orally. T(max) occurred at 0.111+/
      0.068 h orally. The area under the curve (AUC(0-infinity)) i.v. was 895+/-189 and
      373+/-217 ng*h/mL orally. The volume of distribution (V(d[area])) i.v. was 5.50+/
      2.66 L/kg. Total body clearance (Cl) i.v. was 4.62+/-1.09 h; Cl/F for oral
      administration was 39.5+/-23 L/h/kg. The i.v. mean residence time (MRT) was
      0.720+/-0.264. Oral adsorption (F) was low (5.9-19.1%) at almost three times the
      i.v. dosage with a large inter-subject variation. This may be due to binding with
      the rumen contents or enzymatic destruction. Assuming linear nonsaturable
      pharmacokinetics and absorption processes, a dosage of 6.7 times orally would be
      needed to achieve the same i.v. serum concentration of tramadol. The t(1/2) of
      all three metabolites was longer than the parent drug; however, O-DMT, N-DMT, and
      Di-DMT metabolites were not detectable in all of the alpacas. Because of the poor
      bioavailability and adverse effects noted in this study, the oral administration
      of tramadol in alpacas cannot be recommended without further research.

PMID- 21883287
TI  - Active ROP2 GTPase inhibits ABA- and CO2-induced stomatal closure.
AB  - ROP GTPases function as molecular switches in diverse cellular processes.
      Previously, we showed that ROP2 GTPase is activated upon light irradiation, and
      thereby negatively regulates light-induced stomatal opening. Here we studied the
      role of ROP2 during stomatal closure. The expression of a constitutively active
      form of ROP2 (CA-rop2) in Arabidopsis thaliana and Vicia faba resulted in slower
      and reduced stomatal closure in response to abscisic acid (ABA) and CO(2) . In
      contrast, the expression of a dominant-negative form of ROP2 (DN-rop2) and the
      knockout mutation of ROP2 (rop2 KO) promoted ABA-induced stomatal closure in
      Arabidopsis. As early as 10 min after ABA treatment, ROP2 was inactivated and
      translocated to the cytoplasm of the stomatal guard cells. To elucidate the
      mechanism by which active ROP2 suppresses stomatal closure, we monitored
      endocytotic membrane trafficking, which is regulated by Rho GTPases in animal
      cells. We found that the endocytosis of plasma membrane (PM), as tracked by FM4
      64, was lower in CA-rop2-expressing guard cells than in those of wild-type
      plants, which suggests that active ROP2 suppresses the endocytotic
      internalization of PM, a process required for stomatal closure. Together, our
      results suggest that ROP2 is inactivated by ABA, and that this inactivation is
      required for the timely stomatal closure.

PMID- 21883286
TI  - JA-Ile signalling in Solanum nigrum is not required for defence responses in
      nature.
AB  - Jasmonate signalling plays a central role in activating the plethora of responses
      that are elicited by herbivory. Solanum nigrum plants silenced in the expression
      of genes involved in jasmonic acid biosynthesis (irlox3), conjugation (irjar4)
      and perception (ircoi1) were used to study the function of these genes in the
      field and in the regulation of transcriptional and metabolic responses. In the
      field, damage from Noctuidea larvae was four- to fivefold higher on irlox3 and
      ircoi1 than on wild-type (WT) plants, whereas damage to irjar4 plants was similar
      to WT levels. Damage rates reflected plant survival rates; fewer irlox3 (78%) and
      ircoi1 (22%) plants survived compared with irjar4 and WT plants of which all
      plants survived. Gene expression profiling in leaves 3 h after simulated
      herbivory revealed differential regulation of ~700 genes in irlox3 and ircoi1
      plants but of only six genes in irjar4 compared with WT plants. Surprisingly,
      transcriptional responses were not reflected in metabolomic responses; 48 h after
      simulated herbivory, irjar4 plants showed a 50% overlap in their metabolic
      profile with ircoi1 plants. Together, these results reveal that SnJAR4 does not
      play a direct role in herbivore defence, but suggests that SnJAR4 is involved in
      responses other than those to herbivory.

PMID- 21883288
TI  - Using a biochemical C4 photosynthesis model and combined gas exchange and
      chlorophyll fluorescence measurements to estimate bundle-sheath conductance of
      maize leaves differing in age and nitrogen content.
AB  - Bundle-sheath conductance (g(bs) ) affects CO(2) leakiness, and, therefore, the
      efficiency of the CO(2) -concentrating mechanism (CCM) in C(4) photosynthesis.
      Whether and how g(bs) varies with leaf age and nitrogen status is virtually
      unknown. We used a C(4) -photosynthesis model to estimate g(bs) , based on
      combined measurements of gas exchange and chlorophyll fluorescence on fully
      expanded leaves of three different ages of maize (Zea mays L.) plants grown under
      two contrasting nitrogen levels. Nitrogen was replenished weekly to maintain leaf
      nitrogen content (LNC) at a similar level across the three leaf ages. The
      estimated g(bs) values on leaf-area basis ranged from 1.4 to 10.3 mmol m(-2) s(
      1) and were affected more by LNC than by leaf age, although g(bs) tended to
      decrease as leaves became older. When converted to resistance (r(bs) = 1/g(bs)),
      r(bs) decreased monotonically with LNC. The correlation was presumably associated
      with nitrogen effects on leaf anatomy such as on wall thickness of bundle-sheath
      cells. Despite higher g(bs), meaning less efficient CCM, the calculated loss due
      to photorespiration was still low for high-nitrogen leaves. Under the condition
      of ambient CO(2) and saturating irradiance, photorespiratory loss accounted for 3
      5% of fixed carbon for the high-nitrogen, versus 1-2% for the low-nitrogen,
      leaves.

PMID- 21883289
TI  - Whole organ, venation and epidermal cell morphological variations are correlated
      in the leaves of Arabidopsis mutants.
AB  - Despite the large number of genes known to affect leaf shape or size, we still
      have a relatively poor understanding of how leaf morphology is established. For
      example, little is known about how cell division and cell expansion are
      controlled and coordinated within a growing leaf to eventually develop into a
      laminar organ of a definite size. To obtain a global perspective of the cellular
      basis of variations in leaf morphology at the organ, tissue and cell levels, we
      studied a collection of 111 non-allelic mutants with abnormally shaped and/or
      sized leaves, which broadly represent the mutational variations in Arabidopsis
      thaliana leaf morphology not associated with lethality. We used image-processing
      techniques on these mutants to quantify morphological parameters running the
      gamut from the palisade mesophyll and epidermal cells to the venation, whole leaf
      and rosette levels. We found positive correlations between epidermal cell size
      and leaf area, which is consistent with long-standing Avery's hypothesis that the
      epidermis drives leaf growth. In addition, venation parameters were positively
      correlated with leaf area, suggesting that leaf growth and vein patterning share
      some genetic controls. Positional cloning of the genes affected by the studied
      mutations will eventually establish functional links between genotypes, molecular
      functions, cellular parameters and leaf phenotypes.

PMID- 21883290
TI  - Immune responses elicited by co-immunization of Plasmodium vivax and P.
      falciparum MSP-1 using prime-boost immunization strategies.
AB  - Carboxy-terminus of merozoite surface protein-1 (MSP-1(19) ) is the major protein
      on the surface of the plasmodial merozoite that acts as one of the most important
      blood-stage vaccine candidates. The present investigation was designed to
      evaluate the immune responses when either two recombinant antigens (rPvMSP-1(19)
      + rPfMSP-1(19)) or two plasmid constructs (pcDNA3.1 hygro-PvMSP-1(19) + pcDNA3.1
      hygro-PfMSP-1(19)) were administered in combination at a single site in mice by
      using different immunization strategies (protein/protein, DNA/DNA and
      DNA/protein) at weeks 0, 5 and 8. All mice were monitored for the level of MSP
      1(19) -specific antibody for up to 40 weeks. The inclusion of both recombinant
      antigens in a vaccine mixture could not inhibit induction of antibodies to the
      other antigen when the two recombinant antigens were combined in immunization
      formulation. Interestingly, antisera from immunized mice with either recombinant
      antigen failed to cross-react with heterologous antigen. Moreover, the results of
      this study showed that co-immunization with both antigens at a single site
      generated a substantial PvMSP-1(19) - and PfMSP-1(19) -specific antibody
      responses and also IFN-gamma cytokine production (Th1 response) in DNA/protein
      prime-boost immunization strategies. The increased humoral response to PvMSP
      1(19) and PfMSP-1(19) lasted nearly a year after immunization. Therefore, the
      results of this study are encouraging for the development of multi-species
      malaria vaccine based on MSP-1(19) antigen.

PMID- 21883291
TI  - The clinician-scientist: professional dynamics in clinical stem cell research.
AB  - Clinical applications of biomedical research rely on specialist knowledge
      provided by professionals who straddle research and therapy, and possess both
      medical and scientific expertise. To date, this professional group remains under
      explored in sociology. Our article presents a case study of clinician-scientists
      working in stem cell research for heart repair in the UK and Germany who are
      engaged in double-blind randomised clinical trials using patients' own stem
      cells. The analysis draws on sociological and medical literature, interviews and
      ethnographic fieldwork to analyse the experiences and self-rationalisations of a
      small number of clinician-scientists and the ways in which these professionals
      portray, explain and justify their role in the wider clinical research
      environment. We examine our participants' views on the clinical trials they
      conduct, the challenges they encounter and the ways through which they negotiate
      a complex disciplinary terrain, and argue that the recent clinical implementation
      of stem cell research brings clinician-scientists to the fore and provides a
      renewed platform for their professional legitimisation. The article helps
      increase our understanding of how randomised clinical trials are involved in
      consolidating the individual status of actors and the collective standing of
      clinician-scientists as leaders of change in translational medicine.

PMID- 21883292
TI  - The injured and diseased farmer: occupational health, embodiment and technologies
      of harm and care.
AB  - Occupational health in agriculture is a significant public health issue in
      industrialised agricultural nations. This article reports on 26 in-depth
      interviews with farmers throughout New Zealand. Farmers are exposed to a range of
      technologies which place them at risk of injury and disease and/or prevent injury
      and disease. In this article these technologies are respectively conceptualised
      as technologies of harm and technologies of care. Despite being vulnerable to
      high rates of injury, fatality and occupationally related diseases the uptake of
      technologies of care amongst farmers in New Zealand is poor. The analysis draws
      on body theory to explore the meaning attached to injury and disease and to
      examine the socio-cultural field of agriculture. It is argued that the key
      features of subjective embodiment and social, cultural and symbolic capital can
      undermine the uptake of technologies of care, ensuring poor occupational health
      outcomes on New Zealand farms.

PMID- 21883293
TI  - From contact angle titration to chemical force microscopy: a new route to assess
      the pH-dependent character of the stratum corneum.
AB  - Despite of its complex multicomponent organization and its compact architecture,
      the Stratum corneum (SC) is not completely impermeable to substances directly
      applied on the skin surface. A huge number of works have been dedicated to the
      understanding of the mechanisms involved in substance permeation by exploring
      deeper layers than the SC itself. Surprisingly, there is a poor interest in
      studies relating to interactions which may occur in the near-surface region (i.e.
      approximately 1 nm depth) of the SC. In this work, equilibrium proton-transfer
      reactions have been used as probes to define in a fundamental point of view the
      nature of the SC interactions with its environment. Such titration curves are
      investigated on 'in vitro' SC (isolated SC from abdominal skin tissue) and on 'in
      vivo' volar forearm (a sebum poor area). The results are discussed in term of
      work of adhesion and surface pKa values. Because SC can 'reconstruct' under
      heating, influence of the temperature on titration curves is investigated and the
      role of the different components is discussed. Different sigmoidal transitions
      were observed. Two common pKa values (pKa(1) = 4 and pKa(2) = 11.5) were clearly
      identified in both cases and associated to an acid-base character. By playing
      with the temperature of 'in vitro' SC, the 'accessibility' of polar functions was
      increased, thus refining the results by revealing an amphoteric character with an
      acid-to-base transition at pH 3.5 and two acid transitions at pH = 6.5 and pH =
      11.5. Adhesion forces between an Atomic Force Microscopy (AFM) tip and a single
      isolated corneocyte through buffered liquid media were also investigated to
      better understand the role of the individual corneocytes.

PMID- 21883294
TI  - Identification of an emulsifier and conditions for preparing stable nanoemulsions
      containing the antioxidant astaxanthin.
AB  - In this study, oil-in-water nanoemulsions of astaxanthin were prepared by high
      pressure homogenization. The influence of emulsifying conditions including
      emulsifier type, concentration, passing time, astaxanthin concentration and
      coantioxidants were optimized. The stabilities of nanoemulsions were measured
      using zetasizer, FF-SEM, TEM, colorimeter and particle size analyzer. The mean
      diameter of the dispersed particles containing astaxanthin ranged from 160 to 190
      nm. The size distribution was unimodal and extended from 100 to 200 nm. The
      nanoemulsions prepared with glyceryl citrate/lactate/linoleate/oleate (glyceryl
      ester) had smaller particle size and narrower size distribution than the emulsion
      prepared with hydrogenated lecithin. Stable incorporation of astaxanthin in
      nanoemulsion was performed and checked using HPLC, FF-SEM and TEM. The
      nanoemulsion was not significantly affected during storage under light and
      thermal condition for one month indicating that the nanoemulsion had a zeta
      potential of less than -41 mV, indicating a stable colloid.

PMID- 21883296
TI  - Inferior alveolar nerve injury resulting from overextension of an endodontic
      sealer: non-surgical management using the GABA analogue pregabalin.
AB  - AIM:   To describe a case of endodontic sealer (AH Plus) penetration within the
      mandibular canal after root canal treatment with resolution of pain and
      paraesthesia after a non-surgical approach, including treatment with prednisone
      and pregabalin. SUMMARY:   A 37-year-old woman underwent root canal treatment of
      the left mandibular second molar tooth. Postoperative periapical radiographs
      revealed the presence of radiopaque canal sealer in the mandibular canal. The day
      after, the patient reported severe pain in the tooth and paraesthesia/anaesthesia
      in the region innervated by the left inferior alveolar and mental nerve.
      Diagnosis of injury to the inferior alveolar nerve because of extrusion of AH
      Plus was established. The non-surgical management included 1 mg kg(-1) per day
      prednisone, two times per day, in a regimen on a daily basis, and 150 mg per day
      pregabalin, two doses per day, monitoring the progress with periodic follow-up
      visits. One month after the incident, the signs and symptoms were gone. KEY
      LEARNING POINTS: This case illustrates the care required when performing root
      canal treatment, especially when the root apices are in close proximity to the
      inferior alveolar nerve canal. The complete resolution of paraesthesia and the
      control of pain achieved in the present case suggests that a non-surgical
      approach combining prednisone and pregabalin is a good option in the management
      of the inferior alveolar when it is contacted by extruded root filling material.

PMID- 21883295
TI  - Bacterial killing by several root filling materials and methods in an ex vivo
      infected root canal model.
AB  - AIM: To evaluate the ability of two root canal sealers (Epoxy resin-based AH Plus
      or polydimethylsiloxane-based GuttaFlow) and five root filling techniques
      (continuous wave of condensation, Thermafil, lateral condensation, matched taper
      single gutta-percha point, laterally condensed-matched taper gutta-percha point)
      to kill bacteria in experimentally infected dentinal tubules. METHODOLOGY: An
      infected dentine block model was used. One hundred and twenty extracted, single
      rooted human teeth were randomly divided into 10 test (n = 10) and 2 control (n =
      10) groups. The roots, except negative controls, were infected with Enterococcus
      faecalis for 21 days. The root canals were then filled using the test materials
      and methods. Positive controls were not filled. Sterile roots were used as
      negative controls. Dentine powder was obtained from all root canals using gates
      glidden drills using a standard method. The dentine powder was diluted and
      inoculated into bacterial growth media. Total colony-forming units (CFU) were
      calculated for each sample. Statistical analysis was performed using the Kruskal
      Wallis and Mann-Whitney U test. RESULTS: The epoxy resin-based sealer was
      effective in killing E. faecalis except when using Thermafil (P < 0.05), but the
      polydimethylsiloxane-based sealer was not effective in killing this microorganism
      except in the continuous wave group (P < 0.05). CONCLUSIONS: In the test model,
      AH Plus killed bacteria in infected dentine more effectively than GuttaFlow. The
      filling method was less important than the sealer material.

PMID- 21883297
TI  - The attitudinal consequences of thought suppression: a focus on thinness
      thoughts.
AB  - Four studies examined whether thought suppression could enhance attitude
      accessibility and whether behaviours that are consistent with the more accessible
      attitudes would follow. Thinness was examined as the attitude object. Experiments
      1 and 2 showed that suppression of positive thoughts about thinness increased the
      accessibility of the positive attitudes associated with thinness. Experiments 3
      and 4 showed that suppression of positive thinness thoughts also elicited more
      health-promoting behaviours. The implications of the findings for attitude
      accessibility and the practical consequences of thought suppression are
      discussed.

PMID- 21883298
TI  - Collective symbolic coping with disease threat and othering: a case study of
      avian influenza.
AB  - Much research studies how individuals cope with disease threat by blaming out
      groups and protecting the in-group. The model of collective symbolic coping (CSC)
      describes four stages by which representations of a threatening event are
      elaborated in the mass media: awareness, divergence, convergence, and
      normalization. We used the CSC model to predict when symbolic in-group protection
      (othering) would occur in the case of the avian influenza (AI) outbreak. Two
      studies documented CSC stages and showed that othering occurred during the
      divergence stage, characterized by an uncertain symbolic environment. Study 1
      analysed media coverage of AI over time, documenting CSC stages of awareness and
      divergence. In Study 2, a two-wave repeated cross-sectional survey was conducted
      just after the divergence stage and a year later. Othering was measured by the
      number of foreign countries erroneously ticked by participants as having human
      victims. Individual differences in germ aversion and social dominance orientation
      interacted to predict othering during the divergence stage but not a year later.
      Implications for research on CSC and symbolic in-group protection strategies
      resulting from disease threat are discussed.

PMID- 21883299
TI  - The fast and the dangerous: the speed of events influences risk judgements.
AB  - A risk-as-feelings approach suggests that factors irrelevant to the potential
      risk can influence risk perception. This investigation focused on the speed of
      events as one such factor. Negative events that occur relatively quickly were
      judged as more likely to occur than events that occur more slowly. Speed
      influenced risk perception when it was salient and differences in risk perception
      were reduced when it was not salient. Further, the likelihood of a negative
      outcome was judged to be more likely when the same event was described as
      occurring relatively quickly compared to slowly. Even when only the speed at
      which information was presented changed, faster events were judged to be riskier
      than slower events. Theoretically, these findings suggest that speed of an event
      contributes to risk judgements and suggest speed may be the reason people fear
      fast but low incidence events and fail to fear slower but higher incidence
      events.

PMID- 21883300
TI  - Friendship trumps ethnicity (but not sexual orientation): comfort and discomfort
      in inter-group interactions.
AB  - An experience sampling study tested the degree to which interactions with out
      group members evoked negative affect and behavioural inhibition after controlling
      for level of friendship between partners. When friendship level was statistically
      controlled, neither White nor Black participants reported feeling more discomfort
      interacting with ethnic out-group members compared to ethnic in-group members.
      When partners differed in sexual orientation, friendship level had a less
      palliating effect. Controlling for friendship, both gay and straight men - but
      not women - felt more behaviourally inhibited when interacting with someone who
      differed in sexual orientation, and heterosexual participants of both genders
      continued to report more negative affect with gay and lesbian interaction
      partners. However, gay and lesbian participants reported similar levels of
      negative affect interacting with in-group (homosexual) and out-group
      (heterosexual) members after friendship level was controlled. Results suggest
      that much of the discomfort observed in inter-ethnic interactions may be
      attributable to lower levels of friendship with out-group partners. The
      discomfort generated by differences in sexual orientation, however, remains a
      more stubborn barrier to comfortable inter-group interactions.

PMID- 21883301
TI  - Backbiting and bloodshed in books: short-term effects of reading physical and
      relational aggression in literature.
AB  - The current research consisted of two studies examining the effects of reading
      physical and relational aggression in literature. In both studies, participants
      read one of two stories (containing physical or relational aggression), and then
      participated in one of two tasks to measure aggression. In Study 1, participants
      who read the physical aggression story were subsequently more physically
      aggressive than those who read the relational aggression story. Conversely, in
      Study 2, participants who read the relational aggression story were subsequently
      more relationally aggressive than those who read the physical aggression story.
      Combined, these results show evidence for specific effects of reading aggressive
      content in literature.

PMID- 21883302
TI  - Upward and downward comparison in the intermediate-status group: the role of
      social stratification stability.
AB  - This work analyses intergroup comparison choices made by intermediate-status
      group members. Seventy-six psychology students were categorized in an
      intermediate position with respect to other faculties. Stability was manipulated
      at three levels: stable, upwardly unstable, and downwardly unstable. Data on
      strength of comparison, comparison for enhancing, comparison for evaluation, and
      ingroup identification were collected. Results revealed that in the stable
      condition, participants were equally engaged in both upward and downward
      comparison. In the upwardly unstable condition, participants were more likely to
      compare themselves with the high-status group, whereas in the downwardly unstable
      condition, they were more likely to choose a downward comparison. In this latter
      condition, both downward comparison for enhancement and in-group identification
      were lower than in other conditions.

PMID- 21883303
TI  - To the Editor:

PMID- 21883305
TI  - To the Editor:

PMID- 21883306
TI  - To the Editor:

PMID- 21883307
TI  - To the Editor:

PMID- 21883308
TI  - Arrhythmia detection after atrial fibrillation ablation: value of incremental
      monitoring time.
AB  - BACKGROUND: After pulmonary vein isolation (PVI), patients need to be followed to
      analyze the effect of the treatment. We evaluated the influence of the duration
      of Holter monitoring on the detection of arrhythmia recurrences after a single
      PVI at 12 months. METHODS: Consecutive patients with paroxysmal atrial
      fibrillation (AF) underwent successful PVI with phased radiofrequency and
      pulmonary vein ablation catheter. Follow-up was performed with electrocardiogram
      at 3, 6, and 12 months and 7-day Holter at 12 months. Symptomatic patients
      received additional event recording. The 7-day Holters at 12 months were
      evaluated for documented left atrial tachyarrhythmia recurrences, and each
      individual day with AF was categorized. RESULTS: At 12 months after the
      procedure, 21 of the 96 (22%) patients had AF on their 7-day Holter. In the
      patients with AF recurrence, there was an increase in sensitivity from 53% of a 1
      day Holter up to 88% with 4-day Holter, and 100% of a 7-day Holter. Monitoring
      with duration of less than 4 days resulted in significantly less detection of
      patients with AF compared to 7-day Holter. CONCLUSIONS: A 4-day Holter at 12
      months has an 88% sensitivity for arrhythmia detection, and appears to provide a
      sufficient monitoring time. Prolonging the monitoring time to 7 days does not
      significantly increase the yield.

PMID- 21883309
TI  - Alternating bundle branch block.

PMID- 21883310
TI  - Overcoming artifacts and fears: electrophysiology study and radiofrequency
      ablation in a Parkinsonian patient with supraventricular tachycardia and a brain
      neurostimulator.
AB  - With the ageing of the population and expanding use of deep brain stimulation in
      the treatment of various neurological and neuropsychiatric conditions, there will
      be an increasing number of patients with these devices who present with cardiac
      conditions necessitating electrophysiology studies (EPS). However,
      neurostimulator devices have been shown to cause significant artifacts on
      electrocardiography recordings. We present the case of a 53-year-old Parkinsonian
      woman with a brain neurostimulator device who underwent a successful EPS with
      radiofrequency ablation.

PMID- 21883311
TI  - Learning without burning: emerging knowledge of the autonomic innervation of the
      heart.

PMID- 21883312
TI  - Eccentric retrograde atrial activation in a patient with typical atrial flutter.

PMID- 21883313
TI  - Inappropriate therapy delivered by a CRT-D for tachycardia with simultaneous
      atrial and ventricular activation: what is the tachycardia?

PMID- 21883314
TI  - "Pseudo PJRT"--fast-slow AV nodal reentrant tachycardia presenting with
      tachycardia-induced cardiomyopathy.
AB  - A 52-year-old woman presented with left ventricular (LV) dysfunction and
      incessant narrow complex tachycardia. Electrocardiogram and clinical picture were
      suggestive of a permanent form of junctional reciprocating tachycardia, but
      electrophysiology study showed the tachycardia to be a fast-slow form of
      atrioventricular nodal reentrant tachycardia (AVNRT). Slow pathway ablation
      terminated the tachycardia and the LV dysfunction resolved completely at follow
      up. Fast-slow AVNRT has not been reported to present in incessant form, and the
      mechanism in this patient was absent retrograde fast pathway conduction resulting
      in easy initiation and maintenance of tachycardia.

PMID- 21883315
TI  - The impact of pharmacologic sympathetic and parasympathetic blockade on atrial
      electrogram characteristics in patients with atrial fibrillation.
AB  - BACKGROUND: Ablation of atrial autonomic inputs exerts antifibrillatory effects.
      However, because ablation destroys both myocardium and nerve cells, the effect of
      autonomic withdrawal alone remains unclear. We therefore examined the effects of
      pharmacologic autonomic blockade (PAB) on frequency and fractionation in patients
      with atrial fibrillation (AF). METHODS: Esmolol and atropine were administered
      and electrograms were recorded simultaneously from both atria and the coronary
      sinus. In 17 patients, AF was recorded for 5 minutes and dominant frequency (DF)
      and continuous activity (CA) were compared before and during PAB. RESULTS:
      Examination of the pooled data (537 sites, 17 patients) revealed a statistically
      significant decrease in mean DF (5.61-5.43Hz, P < 0.001) during PAB. Site-by-site
      analysis showed that 67% of sites slowed (0.45 +/- 0.59 Hz), whereas 32%
      accelerated (0.49 +/- 0.59Hz). Fractionation was reduced: median CA decreased
      from 31% to 26% (P < 0.001). In patient-by-patient analysis, mean DF/median CA
      decreased in 13 of 17 patients and increased in four. The spatial heterogeneity
      of DF decreased in nine of 17 patients (spatial coefficient of variation of DF at
      "nondriver sites" decreased by a mean of 2%). CONCLUSION: PAB decreases DF and CA
      in the majority of sites. Given the complexity of interactions between atrial
      cells during AF, the effects of PAB on DF and fractionation are more
      heterogeneous than the effects of PAB on isolated cells.

PMID- 21883317
TI  - Intraaortic balloon pump timing discrepancies in adult patients.
AB  - The objective of this clinical study was to quantify the incidence and magnitude
      of intraaortic balloon pump (IABP) inflation and deflation landmark discrepancies
      associated with the IABP catheter arterial pressure waveform. Cardiac surgery
      patients with an IABP inserted prior to surgery were recruited. Following cardiac
      exposure, a high-fidelity pressure catheter was inserted into the aortic root for
      digital recording. The radial artery pressure signal was simultaneously recorded
      from the patient monitor along with the arterial pressure and electrocardiogram
      waveforms from the IABP console while operating at 1:1 and 1:2 synchronization.
      In selected patients, recordings were obtained with the IABP timed to the high
      fidelity aortic root waveform. In all 11 patients, inflation and deflation
      landmark delays were observed when comparing the aortic root waveforms to the
      IABP arterial pressure waveforms (inflation delay = 74 +/- 29 [23-117] ms;
      deflation delay = 71 +/- 37 [24-141] ms, mean +/- standard deviation [min-max]).
      Delays were greater when compared to the radial artery waveform (inflation delay
      = 175 +/- 50 [100-233] ms; deflation delay = 168 +/- 52 [100-274] ms). In all
      cases, the landmark delays were statistically different from zero (P < 0.001).
      Diastolic augmentation and afterload reduction varied with waveform source.
      Conflicting indications of afterload reduction occurred in four patients. Timing
      to the aortic root waveform resulted in greater diastolic pressure augmentation
      and afterload reduction but mixed changes in stroke volume. Delay and distortion
      of the arterial waveform was consistently found when measured through the IABP
      catheter lumen. These delays can alter IABP efficacy and may be eliminated by
      using high-fidelity sensing of aortic pressure.

PMID- 21883316
TI  - Impact of scar, viable myocardium, and epicardial fat on substrate identification
      of ventricular tachycardia in a case with nonischemic cardiomyopathy.
AB  - A 56-year-old man with nonischemic cardiomyopathy underwent orthotopic cardiac
      transplantation after endocardial and epicardial radiofrequency catheter ablation
      for pleomorphic ventricular tachycardia. The myocardial substrate and epicardial
      fat were comprehensively analyzed with three-dimensional electroanatomic maps,
      late gadolinium enhanced ex-vivo cardiac magnetic resonance, and histological
      examination. The association of scar, viable myocardium, and epicardial fat with
      endocardial and epicardial electrogram voltage and duration was quantitatively
      defined. This case provides a unique opportunity to explore the reliability of
      electrical surrogates of scar in nonischemic cardiomyopathy.

PMID- 21883318
TI  - Pseudomonas aeruginosa in a hydropathic facility: diversity, susceptibility and
      imipenem resistance mutation.
AB  - AIMS: To detect Pseudomonas aeruginosa in water and treatment equipment biofilms
      of a thermae hydropathic facility and to study antibiotic susceptibility and
      genetic diversity. METHODS AND RESULTS: One hundred and fifty-four planktonic
      isolates were obtained from 2220 water samples during 4 years. Seventy-two
      biofilm isolates were obtained from 23 samples of inner parts of three inhalation
      equipments. Antibiotic susceptibility was determined by disc diffusion. All
      isolates were susceptible to tested antimicrobials, except two biofilm isolates
      and one planktonic isolate. Twenty-one resistant mutants were observed (nine from
      biofilms), mostly with imipenem (IP) resistance (81%), by diminished expression
      of OprD porin, as it was observed by sodium dodecyl sulfate-polyacrylamide gel
      electrophoresis (SDS-PAGE). Random amplification polymorphic DNA showed a
      genetically heterogeneous population that is spread through the entire system and
      persistent in time. IP resistance mutation ability was spread through the
      population. CONCLUSIONS: The permanent assessment of Ps. aeruginosa is necessary
      not only in water, as expressed in official programmes, but also in equipments
      where biofilms are evident. Ps. aeruginosa was more prevalent in biofilm
      populations and presented higher ability to adapt to antibiotic pressure.
      SIGNIFICANCE AND IMPACT OF THE STUDY: Twenty-one million people use thermae in
      Europe. Official microbiological quality control programmes only consider water
      surveillance. Present study proves the need of a review on current official
      programmes.

PMID- 21883319
TI  - Evolution-based strategy to generate non-genetically modified organisms
      Saccharomyces cerevisiae strains impaired in sulfate assimilation pathway.
AB  - AIMS: An evolution-based strategy was designed to screen novel yeast strains
      impaired in sulfate assimilation. Specifically, molybdate and chromate resistance
      was used as selectable phenotype to select sulfate permease-deficient variants
      that unable to produce sulfites and hydrogen sulfide (H(2) S). METHODS AND
      RESULTS: Four Saccharomyces cerevisiae parent strains were induced to sporulate.
      After tetrad digestion, spore suspensions were observed under the microscope to
      monitor the conjugation of gametes. Then, the cell suspension was inoculated in
      tubes containing YPD medium supplemented with ammonium molybdate or potassium
      chromate. Forty-four resistant strains were obtained and then tested in
      microvinifications. Three strains with a low sulfite production (SO2 < 10 mg l(
      1)) and with an impaired H2S production in grape must without added sulfites were
      selected. CONCLUSIONS: Our strategy enabled the selection of improved yeasts with
      desired oenological characteristics. Particularly, resistance to toxic analogues
      of sulfate allowed us to detect strains that unable to assimilate sulfates.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This strategy that combines the sexual
      recombination of spores and application of a specific selective pressure provides
      a rapid screening method to generate genetic variants and select improved wine
      yeast strains with an impaired metabolism regarding the production of sulfites
      and H2S.

PMID- 21883320
TI  - Comparison of loop-mediated isothermal amplification and real-time PCR for the
      diagnosis of tuberculous pleurisy.
AB  - AIMS: Tuberculous pleurisy is an important cause of pleural effusions in areas
      with a high incidence of tuberculosis. In this study, we developed an IS1081
      based LAMP for the detection of Mycobacterium tuberculosis complex and
      investigated its usefulness in the diagnosis of tuberculous pleurisy. METHODS AND
      RESULTS: Investigation of pleural effusion samples from patients with tuberculous
      pleurisy, majority of them smear-/culture-negative, and control individuals with
      non-TB diseases showed that the LAMP assay with incubation time of 60 min has
      much higher specificity and the LAMP assay with incubation time of 90 min has
      significantly higher sensitivity in the diagnosis of tuberculous pleurisy, as
      compared with fluorescent real-time PCR. CONCLUSIONS: The MTBC-LAMP is a useful
      assay for the diagnosis of tuberculous pleurisy, especially in pleural effusion
      smear-/culture-negative patients. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Tuberculous pleural effusion usually contains low number of mycobacteria, which
      leads to low diagnostic sensitivity of acid-fast staining and mycobacterial
      culture methods. In this study, we developed a simple and sensitive LAMP assay
      for the diagnosis of tuberculous pleurisy. This assay should have broad
      application in resource-limited settings.

PMID- 21883321
TI  - Microbial contamination of food products consumed by infants and babies in Korea.
AB  - AIMS: The objectives of this study were to investigate the microbiological safety
      of various foods intended for consumption by infants and babies. METHODS AND
      RESULTS: The incidence of Cronobacter spp. and Enterobacteriaceae from powdered
      infant formula (PIF, n = 75) and baby soy milk (n = 10) was examined.
      Additionally, aerobic plate count, coliforms and the prevalence of foodborne
      pathogens were investigated in 230 samples from a variety of infant and baby
      foods, including cereal-based follow-up formulas (FUF), liquid FUF and other
      infant foods. High APCs were observed in nutrient supplements and cereal-based
      FUF. Coliforms were found in 6 (2.6%) products, and Cronobacter spp. was isolated
      in 10 (4.4%) samples, including four PIF and six cereal-based FUF. Bacillus
      cereus was detected in 48 (20.9%) samples: cereal-based FUF items (23.0%), rice
      soups (20.6%), honey samples (40.0%), biscuits (40.0%) and liquid FUF (7.4%).
      CONCLUSIONS: New safety criteria, along with hygienic control measures and
      consumer education strategies, are essential to improve the microbiological
      safety of infant or baby foods. SIGNIFICANCE AND IMPACT OF THE STUDY: This study
      provides comprehensive information about the prevalence and level of
      contamination of infant and baby food products by Cronobacter spp. and other
      major foodborne pathogens.

PMID- 21883322
TI  - Randomised clinical trial: the safety and efficacy of AST-120 in non-constipating
      irritable bowel syndrome - a double-blind, placebo-controlled study.
AB  - BACKGROUND: There is a need for safe and effective treatment options for
      irritable bowel syndrome (IBS). AST-120 (spherical carbon adsorbent) is a non
      absorbed, carbon-based adsorbent with extensive adsorbing capability for
      histamine, serotonin and other substances implicated in IBS pathogenesis. AIM: To
      evaluate the efficacy and safety of AST-120 in non-constipating forms of IBS.
      METHODS: This randomised, double-blind, placebo-controlled trial conducted in the
      US and Belgium enrolled 115 male and female patients fulfilling Rome III criteria
      for IBS; individuals with predominantly constipation symptoms were excluded.
      Subjects were randomised to AST-120 2 g tds or placebo for an 8-week double-blind
      treatment period, followed by a 2-week single-blind placebo washout and 8-week
      single-blind active treatment. The primary efficacy endpoint was the proportion
      of subjects achieving at least a 50% reduction in the number of days with
      abdominal pain compared with baseline. RESULTS: At Week 4, 26.8% of subjects
      treated with AST-120 responded on the primary endpoint vs. 10.2% in the placebo
      arm (P=0.029); at Week 8 response rates were 32.1 and 25.4% respectively (NS).
      More AST-120 treated subjects experienced improvement in bloating and stool
      consistency. These benefits abated when AST-120 was replaced by placebo, and
      resumed once AST-120 was restarted. The frequency of adverse events with AST-120
      were less than or equal to placebo. CONCLUSIONS: AST-120 is safe and well
      tolerated and reduces pain and bloating in non-constipating IBS, although
      beneficial effects may be limited in duration. AST-120 represents a locally
      acting, non-absorbed, novel treatment for IBS and warrants further studies.

PMID- 21883323
TI  - Meta-analysis: ursodeoxycholic acid for primary sclerosing cholangitis.
AB  - BACKGROUND: There is no satisfactory medical treatment for patients with primary
      sclerosing cholangitis. There are conflicting data regarding the clinical benefit
      of high doses of ursodeoxycholic acid (UDCA) in primary sclerosing cholangitis.
      AIM: To evaluate using meta-analysis, if UDCA (standard or high-dose) is useful
      in primary sclerosing cholangitis. METHODS: We searched MEDLINE using the
      textwords 'PSC', 'treatment', 'UDCA' and retrieved all abstracts from the major
      Gastroenterology and Liver meetings. We included randomised clinical trials
      comparing standard or high-dose of UDCA (>15 mg/kg body weight per day) vs.
      placebo or no intervention. End-points: mortality or liver transplantation,
      pruritus, fatigue, cholangiocarcinoma and histological progression. RESULTS: We
      identified eight randomised clinical trials comprising 567 patients. Five used
      standard doses and three high doses of UDCA. There was no significant difference
      in mortality [OR, 0.6 (95% CI, 0.4-1.4)], in pruritus [OR, 1.5 (95% CI, 0.3
      7.2)], in fatigue [OR, 0.0 (95% CI, 0.1-7.7)], in cholangiocarcinoma [OR, 1.7
      (95% CI, 0.6-5.1)] and in histology stage progression [OR, 0.9 (95% CI, 0.34
      2.44)]. No differences were found in the subgroup analyses. CONCLUSION: Neither
      standard nor high-dose UDCA influence favourably the progression of primary
      sclerosing cholangitis.

PMID- 21883324
TI  - Prognostic factors in patients with advanced hepatocellular carcinoma treated
      with sorafenib.
AB  - BACKGROUND: Sorafenib is the new reference standard for patients with advanced
      hepatocellular carcinoma (HCC). AIM: To identify prognostic factors in sorafenib
      treated HCC patients and to evaluate outcomes with respect to liver function.
      METHODS: In this retrospective study, 148 HCC patients received sorafenib 400 mg
      b.d. across 11 Austrian institutions. Seventy-eight HCC patients who received
      best supportive care (BSC) in the pre-sorafenib era served as a control. RESULTS:
      In sorafenib-treated patients, low baseline alpha-fetoprotein, low Child-Pugh
      (CP) score, compensated cirrhosis, and low baseline aspartate aminotransferase
      (AST) were associated with significantly longer overall survival (OS) on
      univariate analysis. CP score and baseline AST remained independent prognostic
      factors on multivariate analysis. In patients with Barcelona Clinic liver Cancer
      (BCLC) stage B or C HCC (sorafenib: n = 139; BSC: n = 39), CP-A patients had a
      median OS of 11.3 (sorafenib [n = 76]) vs. 6.4 (BSC [n = 17]) months (P = 0.010),
      and CP-B patients had a median OS of 5.5 (sorafenib [n = 55]) vs. 1.9 (BSC [n =
      22]) months (P = 0.021). In the sorafenib group, median OS according to baseline
      AST was 11.8 (<100 U/L [n = 58]) vs. 3.9 (>=100 U/L [n = 15]) months for CP-A
      patients (P = 0.127), and 6.5 (<100 U/L [n = 33]) vs. 2.1 (>=100 U/L [n = 21])
      months for CP-B patients (P = 0.011). There was no survival difference between
      sorafenib and BSC in patients with BCLC stage D HCC (1.5 vs. 1.4 months; P =
      0.116). CONCLUSIONS: Sorafenib was associated with improved survival in both CP-A
      and CP-B patients. In CP-B patients, baseline AST may be helpful in determining
      which patients are most likely to benefit from sorafenib.

PMID- 21883325
TI  - Cycled enteral antibiotics reduce sepsis rates in paediatric patients on long
      term parenteral nutrition for intestinal failure.
AB  - BACKGROUND: Long-term parenteral nutrition has transformed the prognosis for
      children suffering from intestinal failure. However, parenteral nutrition itself
      is associated with considerable morbidity and mortality including that caused by
      sepsis. AIM: To examine a strategy of cycled enteral antibiotics in reducing the
      incidence of sepsis in paediatric intestinal failure patients. METHODS:
      Retrospective analysis of the incidence of sepsis rates of patients on long-term
      parenteral nutrition, at a tertiary paediatric hospital. Patients were separated
      into those who received cycled enteral antibiotics and a control group. Sepsis
      rates before and during cycled enteral antibiotics were compared with comparable
      timeframes between the cycled enteral antibiotics and control groups. Central
      venous catheter removal rates were also compared. RESULTS: Fifteen patients
      (eight cycled enteral antibiotics, & seven controls) received 9512 parenteral
      nutrition days, with a total of 132 sepsis episodes. All eight patients of the
      treatment group demonstrated a decrease in the frequency of episodes of sepsis
      following the introduction of cycled enteral antibiotics. The cycled enteral
      antibiotics group had a significant reduction in infection rate during the
      treatment period (from 2.14 to 1.06 per 100 parenteral nutrition days, P = 0.014:
      median effect size -1.04 CI 95%-1.93, -0.22), whereas the controls had no
      significant change (1.91 - 2.36 per 100 parenteral nutrition days P = 0.402:
      median effect size 0.92 CI 95%-1.96, 4.17). The central venous catheter survival
      rates increased in the cycled enteral antibiotics group from 0.44 central venous
      catheter removals per 100 parenteral nutrition days to 0.27 central venous
      catheter removals per 100 parenteral nutrition days, although this was not
      statistically significant. CONCLUSIONS: Cycled enteral antibiotics significantly
      reduced the rate of sepsis in a small group of paediatric intestinal failure
      patients. Larger well-designed prospective studies are warranted to further
      explore this finding.

PMID- 21883326
TI  - Early clinical remission and normalisation of CRP are the strongest predictors of
      efficacy, mucosal healing and dose escalation during the first year of adalimumab
      therapy in Crohn's disease.
AB  - BACKGROUND: Adalimumab is a fully human monoclonal antibody targeting tumour
      necrosis factor with proven efficacy in the treatment of Crohn's disease (CD).
      AIM: To investigate the predictors of medium-term clinical efficacy and mucosal
      healing during adalimumab therapy, in patients with CD, in specialised centres
      approved for biological therapy in Hungary. METHODS: Data capture of the 201 CD
      patients was standardised and prospective (male/female: 112/89, median age: 33.0
      years, duration: 8 years). Previous infliximab therapy had been administered in
      48% of patients, concomitant steroids in 41%, azathioprine in 69% and combined
      therapy in 27% of patients. RESULTS: Overall clinical response and remission
      rates at 24 weeks were 78% and 52%, respectively; at 52 weeks were 69% and 44%,
      respectively. Endoscopic improvement and healing were achieved in 43% and 24% of
      patients. In a logistic regression model, clinical efficacy and CRP at week 12,
      need for combined immunosuppression at induction, shorter disease duration and
      smoking were identified as independent predictors for 12-month clinical outcome,
      whereas CRP at week 12, clinical remission at week 24, inflammatory parameters
      and nonsmoking were associated to endoscopic improvement/healing. Intensification
      to weekly dosing was needed in 16% of patients. Parallel azathioprine therapy and
      clinical remission at week 12 were inversely associated with dose escalation.
      CONCLUSIONS: Clinical efficacy and normalised CRP at week 12 (early deep clinical
      remission) are associated with medium-term clinical efficacy and mucosal healing
      during adalimumab therapy, whereas need for combined immunosuppression at
      induction and smoking status are predictors for non-response. Parallel
      azathioprine therapy may decrease the probability for dose escalation.

PMID- 21883327
TI  - Management options for lamivudine-resistant chronic hepatitis B patients with
      suboptimal virological suppression by adefovir.
AB  - BACKGROUND: In chronic hepatitis B (CHB) patients, adefovir is commonly used as a
      rescue therapy for lamivudine resistance, but often results in incomplete
      virological suppression. AIM: To study the factors predicting response to
      adefovir rescue, and the treatment response of tenofovir and entecavir in
      suboptimal responders to adefovir in CHB patients. METHODS: Chronic hepatitis B
      patients who took adefovir for at least 6 months for lamivudine resistance were
      studied. Early virological response was defined as undetectable HBV DNA at month
      6. Maintained virological response was defined as undetectable HBV DNA till the
      last follow-up. RESULTS: Among 136 patients on adefovir for 39 (5-117) months, 30
      (22%) had early virological response. The 3-year cumulative probability of
      maintained virological response was similar between patients on adefovir
      monotherapy (n = 53, 57.9%) and those on combination of lamivudine and adefovir
      treatment (n = 83, 56.5%). The month 6 HBV DNA was the only independent factor
      associated with maintained virological response (adjusted hazard ratio 0.49, 95%
      confidence interval 0.37-0.65, P < 0.001). Twenty-six of 30 (87%) early
      responders and 36 of 106 (34%) non-early responders had maintained virological
      response on adefovir (P < 0.001). Among 106 non-early responders, 18 and 11 were
      switched to tenofovir and entecavir, respectively. The 1-year cumulative
      probability of maintained virological response was higher in patients switched to
      tenofovir (87.5%) than those switched to entecavir (37.5%; P = 0.048) or
      continued with adefovir (8.7%; P < 0.001). CONCLUSIONS: In adefovir rescue for
      lamivudine resistance, month 6 HBV DNA predicts maintained virological response
      in CHB patients. Switching to tenofovir achieved best viral suppression among
      suboptimal responders to adefovir.

PMID- 21883328
TI  - Irrational use of antibiotics and role of the pharmacist: an insight from a
      qualitative study in New Delhi, India.
AB  - WHAT IS KNOWN AND OBJECTIVE: The overall volume of antibiotic consumption in the
      community is one of the foremost causes of antimicrobial resistance. In
      developing countries like India, pharmacists often dispense 'prescription-only'
      drugs, like antibiotics, to patients who do not have a prescription. Not much
      data is available regarding detailed information on behaviour of antibiotic use
      by community pharmacists which is of particular significance to develop a
      suitable and sustainable intervention programme to promote rational use of
      antibiotics. A qualitative study was conducted to understand the dispensing
      practices and behaviour of community pharmacists to develop policy interventions
      that would improve the use of antibiotics at the community level. METHODS: Focus
      group discussions (FGDs) were held for five municipal wards of Delhi with retail
      pharmacists, public sector pharmacists and the office bearers of pharmacists'
      associations. Data on antibiotic use and resistance were collected earlier from
      these five wards. FGDs (n = 3 with 40 pharmacists) were analysed through grounded
      theory. RESULTS AND DISCUSSION: Four broad themes identified were as follows:
      prescribing and dispensing behaviour; commercial interests; advisory role; and
      intervention strategies for rational use of antibiotics. FGDs with pharmacists
      working in the public sector revealed that, besides the factors listed above,
      overstock and near-expiry, and under-supply of antibiotics promoted antibiotic
      misuse. Suggestions for interventions from pharmacists were the following: (i)
      education to increase awareness of rational use and resistance to antibiotics;
      (ii) involving pharmacists as partners for creating awareness among communities
      for rational use and resistance to antibiotics; (iii) developing an easy return
      policy for near-expiry antibiotics in public sector facilities; and (iv)
      motivating and showing appreciation for community pharmacists who participate in
      intervention programmes. WHAT IS NEW AND CONCLUSIONS: Inappropriate antibiotic
      dispensing and use owing to commercial interests and lack of knowledge about the
      rational use of antibiotics and antibiotic resistance were the main findings of
      this in-depth qualitative study. Community pharmacists were willing to
      participate in educational programme aimed at improving use of antibiotics. Such
      programmes should be initiated within a multidisciplinary framework including
      doctors, pharmacists, social scientists, government agencies and non-profit
      organizations.

PMID- 21883329
TI  - Population pharmacokinetics of steady-state carbamazepine in Egyptian epilepsy
      patients.
AB  - WHAT IS KNOWN AND OBJECTIVE: Individualization of carbamazepine (CBZ) dosage
      regimen in patients with epilepsy based on based on therapeutic drug monitoring
      (TDM) followed by estimation of pharmacokinetic (PK) parameters can help in
      better control of epilepsy. Our objective was to establish a population (POP) PK
      model of CBZ for Egyptian adult and pediatric patients with epilepsy. METHOD:
      Single steady-state (SS) trough plasma concentrations of CBZ were available for
      302 patients with epilepsy (55.6% men and 44.4% women) who were categorized as
      children (n = 118) and adults (n = 184) with mean age (years) +/- SD of 10.6 +/-
      4.8 and 29.4 +/- 9.9, respectively. Carbamazepine was given as an oral suspension
      (n = 19) or controlled release tablet (n = 283) with average dose of 15.0 +/- 7.8
      mg/kg per day. A one-compartment model with first-order absorption and
      elimination for SS conditions (ADVAN2, SS2, TRANS2) was applied using NONMEM 6.2.
      Separate absorption rate constants were modelled for the two formulations. The
      mean POP CL, its intersubject variability (ISV), as well as residual error of CBZ
      concentration were estimated. RESULTS AND DISCUSSION: The POP estimate for CL was
      3.5 L/h with coefficient of variation value of 2.6%, which was consistent with
      literature data. The ISV on CL was 44.5%. The POP PK model was validated by
      bootstrap re-sampling, and the individual estimates were within the 95% CI of the
      bootstrap results. Different covariates that might affect CBZ CL have been
      evaluated but the limited number of samples per individual prevented precise
      covariate analysis. WHAT IS NEW AND CONCLUSION: The POP PK model we have
      developed for CBZ shows good predictive performance in Egyptian adult and
      pediatric patients with epilepsy. Another PK study to better define the effect of
      different covariates would improve on the model for dosage individualization.

PMID- 21883330
TI  - Population pharmacokinetics of fluconazole after administration of fosfluconazole
      and fluconazole in critically ill patients.
AB  - WHAT IS KNOWN AND OBJECTIVE: Fluconazole is an antifungal agent that is commonly
      used to treat patients with serious systemic fungal infections in intensive care
      units. Fosfluconazole is a phosphate prodrug of fluconazole, which was developed
      to reduce the volume of fluid required to administer fluconazole by intravenous
      injection. The objective of this study was to characterize the pharmacokinetics
      of the antifungal fluconazole after the intravenous administration of the prodrug
      fosfluconazole or fluconazole in critically ill patients with serious systemic
      fungal infections, by population pharmacokinetic analysis using the nonmem
      software package. METHODS: Clinical biochemical data including serum fluconazole
      levels were obtained from 57 patients treated in the intensive care unit along
      with two naive pooled patients gleaned from previous reports. The pharmacokinetic
      model of fluconazole was estimated using a one-compartment model. The probability
      that the area under the concentration-time curve is higher than 800 MUg h/mL was
      determined by simulation. RESULTS: It was assumed that all the administered
      fosfluconazole was converted to fluconazole with an estimated fosfluconazole
      fluconazole conversion rate constant of 2.05/h. The significant covariates for
      clearance for fluconazole (CL) and volume of distribution for fluconazole (Vd)
      were resulted in creatinine clearance (CLcr) and body weight (BW), respectively,
      in the final pharmacokinetic model equations: CL (L/h) = 0.799 * [CLcr
      (mL/min)/92.7](0.685) and Vd (L) = 48.1 * [BW (kg)/65](1.40) , where the
      interpatient variabilities in CL and Vd and the intrapatient variability were
      44.8%, 79.7% and 19.8%, respectively. On the basis of the results of the Monte
      Carlo simulation, the probabilities of target attainment were 60%, 26% and 11%
      for 400 mg/day administration as fluconazole equivalent at CLcr values of 40, 70
      and 100 mL/min, respectively. WHAT IS NEW AND CONCLUSION: The present population
      pharmacokinetic analysis strongly indicates that fosfluconazole (and fluconazole)
      dosage should be optimized in terms of CLcr in critically ill patients.

PMID- 21883331
TI  - Does fairness matter in the context of anger about nuclear energy decision
      making?
AB  - Several recent studies have questioned whether nonoutcome forms of fairness
      matter in decision-making situations where individuals feel strongly engaged by
      the issue at hand. This survey-based study focuses on perceptions about a
      decision-making process related to a proposal to expand a nuclear power plant in
      the U.S. Southeast. It finds that anger moderates the impacts of outcome and
      procedural fairness on willingness to accept a decision process as satisfactory
      and legitimate. The more anger a person said he or she would feel if a decision
      were to contradict that person's point of view, the more perceived outcome and
      procedural fairness mattered. The study also finds that interpersonal fairness is
      also moderated by anger, but in the opposite direction. Interpersonal fairness
      had less of an impact on willingness to accept a decision for those who said they
      would feel angry if the decision did not go their preferred way.

PMID- 21883332
TI  - The semantic distinction between "risk" and "danger": a linguistic analysis.
AB  - The analysis combines frame semantic and corpus linguistic approaches in
      analyzing the role of agency and decision making in the semantics of the words
      "risk" and "danger" (both nominal and verbal uses). In frame semantics, the
      meanings of "risk" and of related words, such as "danger," are analyzed against
      the background of a specific cognitive-semantic structure (a frame) comprising
      frame elements such as Protagonist, Bad Outcome, Decision, Possession, and
      Source. Empirical data derive from the British National Corpus (100 million
      words). Results indicate both similarities and differences in use. First, both
      "risk" and "danger" are commonly used to represent situations having potential
      negative consequences as the result of agency. Second, "risk" and "danger,"
      especially their verbal uses (to risk, to endanger), differ in agent-victim
      structure, i.e., "risk" is used to express that a person affected by an action is
      also the agent of the action, while "endanger" is used to express that the one
      affected is not the agent. Third, "risk," but not "danger," tends to be used to
      represent rational and goal-directed action. The results therefore to some extent
      confirm the analysis of "risk" and "danger" suggested by German sociologist
      Niklas Luhmann. As a point of discussion, the present findings arguably have
      implications for risk communication.

PMID- 21883333
TI  - Experience with urban air pollution in Paterson, New Jersey and implications for
      air pollution communication.
AB  - Communication about air pollution can help reduce health risks, but a scattered,
      largely qualitative literature on air pollution beliefs, attitudes, and behaviors
      raises questions about its effectiveness. A telephone survey of Paterson, New
      Jersey (USA) residents tested four hypotheses aimed toward integrating these
      findings. Self-reported sheltering indoors during high pollution, the recommended
      strategy, was predicted by perceived air quality and self-reported "sensitivity"
      to air pollution. Nearly a quarter of the sample reported mandatory outdoor
      activity (e.g., work) that might increase their exposures, but this factor did
      not significantly affect self-reported sheltering. Perceptions of air quality did
      not correlate strongly with official monitoring data (U.S. Air Quality Index
      (AQI)); even people who regularly sought AQI data relied upon sensory cues to
      high pollution, and secondarily upon health cues. Use of sensory and health cues,
      definitions of what makes someone sensitive to air pollution, and (less strongly)
      definitions of vulnerability to air pollution varied widely. The minority aware
      of the AQI were more likely to seek it if they had illnesses or saw themselves in
      the targeted AQI audience, yet less likely if they believed themselves sensitive
      to pollution. However, their sense of the AQI's match to their own experience was
      driven by whether they used sensory (yes) or health (no) cues, not by illness
      status. Some urban residents might not have access to AQI data, but this barrier
      seems outweighed by need to bridge interpretive gaps over definitions of air
      pollution, sensory perception, vulnerability, and health consequences.

PMID- 21883334
TI  - Risk assessment of major hazards and its application in urban planning: a case
      study.
AB  - With the rapid development of industry in China, the number of establishments
      that are proposed or under construction is increasing year by year, and many are
      industries that handle flammable, explosive, toxic, harmful, and dangerous
      substances. Accidents such as fire, explosion, and toxic diffusion inevitably
      happen. Accidents resulting from these major hazards in cities cause a large
      number of casualties and property losses. It is increasingly important to analyze
      the risk of major hazards in cities realistically and to suitably plan and
      utilize the surrounding land based on the risk analysis results, thereby reducing
      the hazards. A theoretical system for risk assessment of major hazards in cities
      is proposed in this article, and the major hazard risk for the entire city is
      analyzed quantitatively. Risks of various major accidents are considered
      together, superposition effect is analyzed, individual risk contours of the
      entire city are drawn out, and the level of risk in the city is assessed using
      "as low as reasonably practicable" guidelines. After the entire city's individual
      risk distribution is obtained, risk zones are divided according to corresponding
      individual risk value of HSE, and land-use planning suggestions are proposed.
      Finally, a city in China is used as an example to illustrate the risk assessment
      process of the city's major hazard and its application in urban land-use
      planning. The proposed method has a certain theoretical and practical
      significance in establishing and improving risk analysis of major hazard and
      urban land-use planning. On the one hand, major urban public risk is avoided;
      further, the land is utilized in the best possible way in order to obtain the
      maximum benefit from its use.

PMID- 21883335
TI  - Meta-analysis of mass-balance studies of soil ingestion in children.
AB  - Ingestion of soil by young children may be an important source of exposure to
      environmental contaminants. Estimates of soil ingestion have been made by several
      studies using trace elements in a mass-balance approach, but differ substantially
      between studies and trace elements. We conduct a meta-analysis of four major mass
      balance soil ingestion studies conducted on children between one and seven in the
      summer/fall in the northern United States. The analysis takes advantage of
      primary data from all studies, and provides a more complete description of soil
      ingestion among children. The meta-analysis uses data based on the two most
      reliable trace elements, Al and Si, that have passed a screening to identify and
      exclude measures with a high likelihood of bias. Details are described in a
      companion paper. The best linear unbiased predictor is used in a mixed model to
      estimate soil ingestion for study subjects. Overall, 11% of subject-periods are
      identified as outliers and excluded from the analysis. An analysis on 216
      children based on Al and Si as tracer elements indicates that the mean (median)
      soil ingestion is 26 mg/day (33 mg/day), with the 95th percentile estimated as 79
      mg/day. This systematic approach provides more reliable estimates than individual
      study results. There is some evidence that soil ingestion increases with a
      child's age, but insufficient data to distinguish soil ingestion by gender.

PMID- 21883336
TI  - Fairness and nanotechnology concern.
AB  - Research suggests that fairness perceptions matter to people who are asked to
      evaluate the acceptability of risks or risk management. Two separate national
      random surveys (n = 305 and n = 529) addressed Americans' concerns about and
      acceptance of nanotechnology risk management in the context of the degree to
      which they view scientists and risk managers as fair. The first survey
      investigated general views about scientists across four proposed dimensions of
      fairness (distributional, procedural, interpersonal, and informational). The
      results show that respondents who believe that the outcomes of scientific
      research tend to result in unequal benefits (distributional fairness) and that
      the procedures meant to protect the public from scientific research are biased
      (procedural fairness) were more concerned about nanotechnology. Believing
      scientists would treat them with respect (interpersonal fairness) and ensure
      access to information (informational fairness) were not significant predictors of
      concern. The second study also looked at these four dimensions of fairness but
      focused on perceptions of risk managers working for government, universities, and
      major companies. In addition to concern, it also examined acceptance of
      nanotechnology risk management. Study 2 results were similar to those of study 1
      for concern; however, only perceived informational fairness consistently
      predicted acceptance of nanotechnology risk management. Overall, the study points
      to the value of considering fairness perceptions in the study of public
      perceptions of nanotechnology.

PMID- 21883337
TI  - Risk management in a developing country context: improving decisions about point
      of-use water treatment among the rural poor in Africa.
AB  - More than 1 billion people, the vast majority of which live in the developing
      world, lack basic access to clean water for domestic use. For this reason,
      finding and promoting effective and sustainable solutions for the provision of
      reliable clean water in developing nations has become a focus of several public
      health and international development efforts. Even though several means of
      providing centrally located sources of clean water in developing communities
      exist, the severity and widespread nature of the water problem has led most
      development agencies and sanitation experts to strongly advocate the use of point
      of-use treatment systems alongside whatever source of water people regularly use.
      In doing so, however, development practitioners have been careful to point out
      that any interventions or infrastructure regarding water safety and human health
      must also adhere to one of the central principles of international development:
      to facilitate more democratic and participatory models of decision making and
      governance. To this end, the research reported here focused on the development of
      a deliberative risk management framework for involving affected stakeholders in
      decisions about POU water treatment systems. This research, which was grounded in
      previous studies of structured decision making, took place in two rural villages
      in the East African nation of Tanzania.

PMID- 21883338
TI  - Aperture referral in heterocentric astigmatic systems.
AB  - BACKGROUND: Retinal blur patch, effective corneal patch, projective field, field
      of view and other concepts are usually regarded as disjoint concepts to be
      treated separately. However they have in common the fact that an aperture, often
      the pupil of the eye, has its effect at some other longitudinal position. Here
      the effect is termed aperture referral. PURPOSE: To develop a complete and
      general theory of aperture referral under which many ostensibly-distinct aperture
      dependent concepts become unified and of which these concepts become particular
      applications. The theory allows for apertures to be elliptical and decentred and
      refracting surfaces in an eye or any other optical system to be astigmatic,
      heterocentric and tilted. METHODS: The optical model used is linear optics, a
      three-dimensional generalization of Gaussian optics. Positional and inclinational
      invariants are defined along a ray through an arbitrary optical system. A pencil
      of rays through a system is defined by an object or image point and an aperture
      defines a subset of the pencil called a restricted pencil. RESULTS: Invariants
      are derived for four cases: an object and an image point at finite and at
      infinite distances. Formulae are obtained for the generalized magnification and
      transverse translation and for the geometry and location of an aperture referred
      to any other transverse plane. CONCLUSIONS: A restricted pencil is defined by an
      aperture and an object or image point. The intersection of the restricted pencil
      with a transverse plane is the aperture referred to that transverse plane. Many
      concepts, including effective corneal patch, retinal blur patch, projective field
      and visual field, can now be treated routinely as special cases of the general
      theory: having identified the aperture, the referred aperture and the referring
      point one applies the general formulae directly. The formulae are exact in linear
      optics, explicit and give insight into relationships.

PMID- 21883340
TI  - Implementing nutritional guidelines -- the effect of systematic training for
      nurse nutrition practitioners.
AB  - INTRODUCTION: Approximately 40% of patients admitted to hospitals are
      undernourished. Implementing nutritional guidelines might reduce the incidence of
      malnutrition, and it requires education and training for the hospital staff. AIM:
      It was hypothesised that a training programme focusing on the staff behaviour
      would increase the identification of eating difficulties, improve patients'
      knowledge about appropriate food choices and increase the number of snacks eaten
      between meals and thereby to reduce the risk of undernutrition. METHODS: A pre-
      and post-test design was used to evaluate the effect of the training programme
      for nurses. The training was conducted in five modules over 1 year and combined
      nutritional issues with issues on implementation and theories of planned change.
      The programme was based on experimental learning theories and the steps of look,
      think and act. The effect on the patients was measured by a patient
      questionnaire. RESULTS: After implementing the guidelines, more patients
      discussed their eating difficulties with the staff, received relevant assistance
      during the meal and were served the type of food they had ordered and could chew.
      The patients' knowledge of appropriate food choices from the menu increased,
      suggesting that the nutritional intake of the patients had improved. CONCLUSION:
      Our findings suggest that a strategy based on the principles of experimental
      learning theory and the phases in the look, think and act model facilitated the
      implementation of nutritional guidelines in a hospital setting.

PMID- 21883341
TI  - Organizational differences in early child health care -- mothers' and nurses'
      experiences of the services.
AB  - AIM: The aim of this study was to evaluate parents' and nurses' perceptions of
      the child health services (CHS) in relation to whether the nurse worked
      exclusively with children (focused-child health centre, CHC) vs. with people of
      all ages (mixed-CHC). METHOD: Information about parents' perceptions about the
      CHS was acquired by a questionnaire intended for the mothers of 18-month-old
      children. One thousand thirty-nine answered in the baseline 2002-2003 and 996 in
      the follow-up 2004-2005. The nurses answered a special questionnaire aimed to
      obtain knowledge about their satisfaction with their work. Eighteen CHCs were
      chosen from the county of Uppsala and eighteen from other Swedish counties. The
      CHCs were chosen from areas with poor psycho-social status. The data were
      collected by questionnaires to mothers and nurses, and the analysis used the chi
      square test, t-test and logistic regression. The study was approved by the
      Research Ethics Committees of the universities involved. RESULTS: Mothers were
      more satisfied, and the nurses found their work tasks easier, at CHCs where the
      child health nurse worked exclusively with children, compared with mothers and
      nurses belonging to CHCs where the nurses provided care to people of all ages.
      CONCLUSION: The findings indicated that nurses working exclusively with children,
      being able to concentrate their time and knowledge on a specialized field,
      develop a more solid child health competence. There are strong reasons to
      consider introducing 'exclusive' CHCs in psycho-socially vulnerable areas, which
      would probably make the services more effective. However, intensified education
      may modify the drawbacks of mixed-CHCs.

PMID- 21883342
TI  - The process, logistics and challenges of implementing clinical supervision in a
      generalist tertiary referral hospital.
AB  - Clinical supervision (CS) has been identified within nursing as a process for
      improving clinical practice and reducing the emotional burden of nursing
      practice. Little is known about its implementation across large tertiary referral
      hospitals. The purpose of this study is to evaluate the implementation of
      clinical supervision across several different nursing specialities at a teaching
      hospital in Sydney, Australia. Using a model of nursing implementation science, a
      process was developed at the study site that facilitated the development,
      implementation and evaluation of the project. After a 6-month study period, the
      CS groups were postevaluated using a survey tool developed for the project. A
      total of nine CS groups were in operation over the 6-month study period. A
      predominant focus within the sessions was one of the collegial support and
      developing standards of practice. The process was able to achieve wide hospital
      based support for the role of CS from the senior nurse executives to junior
      nurses. Whilst there was overall positive support for the CS groups, logistical
      and resource challenges remain, in the effective roll out of CS to large numbers
      of nurses.

PMID- 21883343
TI  - Life experiences of Taiwanese oral cancer patients during the postoperative
      period.
AB  - The incidence of oral cancer has rapidly increased in Taiwan. Oral cancer and its
      surgical treatment may also cause physical and psychological problems for
      patients. During the postoperative period, patients face adjustments in their
      disease, treatment and lives. However, research on these relevant issues is
      scant. A qualitative study was conducted with the purpose of exploring the life
      experiences of surgically treated Taiwanese oral cancer patients during the
      postoperative period. Thirteen patients with oral cancer were recruited from the
      otolaryngology head and neck surgery wards of a medical centre in northern
      Taiwan. Semi-structured interviews were conducted and tape recorded after
      informed consent had been obtained. Data were analysed using the content analysis
      method. Results show that the life experiences of the patients with oral cancer
      were related to the impact of threatening symptoms, concerns about survival,
      restriction of interpersonal relationships, self-restructuring and constructing a
      support network. The results of this study can provide healthcare professionals
      with a reference for implementing care plans to address the unique needs of
      patients with oral cancer.

PMID- 21883344
TI  - Self-care ability among home-dwelling older people in rural areas in southern
      Norway.
AB  - INTRODUCTION: The growing number of older people is assumed to represent many
      challenges in the future. Self-care ability is a crucial health resource in older
      people and may be a decisive factor for older people managing daily life in their
      own homes. Studies have shown that self-care ability is closely related to
      perceived health, sense of coherence and nutritional risk. AIM: The aim of this
      study was to describe self-care ability among home-dwelling older individuals
      living in rural areas in southern Norway and to relate the results to general
      living conditions, sense of coherence, screened nutritional state, perceived
      health, mental health and perceived life situation. METHODS: A cross-sectional
      survey was carried out in rural areas in five counties in 2010. A mailed
      questionnaire, containing background variables, health-related questions and five
      instruments, was sent to a randomly selected sample of 3017 older people (65+
      years), and 1050 respondents were included in the study. Data were analysed with
      statistical methods. RESULTS: A total of 780 persons were found to have higher
      self-care ability and 240 to have lower self-care ability using the Self-care
      Ability Scale for the Elderly. Self-care ability was found to be closely related
      to health-related issues, self-care agency, sense of coherence, nutritional state
      and mental health, former profession, and type of dwelling. Predictors for high
      self-care ability were to have higher self-care agency, not receiving family
      help, having low risk for undernutrition, not perceiving helplessness, being able
      to prepare food, being active and having lower age. CONCLUSIONS: When self-care
      ability is reduced in older people, caregivers have to be aware about how this
      can be expressed and also be aware of their responsibility for identifying and
      mapping needs for appropriate support and help, and preventing unnecessary and
      unwanted dependency.

PMID- 21883345
TI  - Abuse in health care: a concept analysis.
AB  - AIMS AND OBJECTIVES: To analyse the concept of abuse in health care. This
      analysis also covers how abuse in health care is different from the related
      concepts of medical error, patient satisfaction and personal identity threat.
      BACKGROUND: Abuse in health care is an emerging concept in need of a clear
      analysis and definition. At the same time, boundaries to the related concepts are
      not demarcated. DESIGN: Concept analysis as developed by Walker and Avant.
      METHOD: The databases Cumulative Index to Nursing and Allied Health Literature,
      Medline, and Google Scholar were used to obtain articles published between 1997
      and 2009. A total of eleven articles are referred to on abuse in health care,
      four on medical error, six on patient satisfaction and three on personal identity
      threat. RESULTS: Abuse in health care is defined by patients' subjective
      experiences of encounters with the health care system, characterized by devoid of
      care, where patients suffer and feel they lose their value as human beings. The
      events are most often unintended. We also found differences with the
      aforementioned related concepts: medical error does not share the patients'
      perspective, and patient satisfaction does not offer room for patients' abusive
      experiences. The concept of personal identity threat shares all attributes with
      abuse in health care, but it lacks an antecedent that signifies the social
      structures underlying the phenomenon. CONCLUSIONS: Abuse in health care covers a
      phenomenon that has severe consequences but is invisible if seen from a medical
      error or patient satisfaction perspective.

PMID- 21883346
TI  - Histological and molecular features of lipomatous and nonlipomatous adipose
      tissue in familial partial lipodystrophy caused by LMNA mutations.
AB  - OBJECTIVES: Type 2 familial partial lipodystrophy (FPLD2) is a rare adipose
      tissue (AT) disease caused by mutations in LMNA, in which lipomas appear
      occasionally. In this study, we aimed to histologically characterize FPLD2
      associated lipomatosis and study the expression of genes and proteins involved in
      cell cycle control, mitochondrial function, inflammation and adipogenesis. DESIGN
      AND PATIENTS: One lipoma and perilipoma fat from each of four subjects with FPLD2
      and 10 control subjects were analysed by optical microscopy. The presence of
      inflammatory cells was evaluated by immunohistochemistry. Real-time RT-PCR and
      Western blot were used to evaluate gene and protein levels. RESULTS: Adipocytes
      from lipodystrophic patients were significantly larger than those of controls, in
      both the lipomas and perilipoma fat. Lipodystrophic AT exhibited CD68(+)
      macrophages and CD3(+) lymphocytes infiltration. TP53 expression was reduced in
      all types of lipomas. At protein level, C/EBPbeta, p53 and pRb were severely
      disturbed in both lipodystrophic lipomas and perilipoma fat coming from
      lipoatrophic areas, whereas the expression of CEBPalpha was normal. Mitochondrial
      function genes were less expressed in lipoatrophic fat. In both lipomas and
      perilipoma fat from lipoatrophic areas, the expression of adipogenes was lower
      than controls. CONCLUSIONS: Even in lipomas, the adipogenic machinery is impaired
      in lipodystrophic fat coming from lipoatrophic regions in FPLD2, although the
      histological phenotype is near-normal, exhibiting low-grade inflammatory
      features. Our results suggest that the p53 pathway and some adipogenic proteins,
      such as CEBPalpha, could contribute to the maintenance of this near normal
      phenotype in the remnant AT present in these patients.

PMID- 21883347
TI  - Functional and structural evaluation of hearing in acromegaly.
AB  - CONTEXT: The impact of acromegaly on the auditory system remains unknown.
      OBJECTIVE: This study aimed to examine audiological symptoms and the structure
      and function of the auditory system in patients with acromegaly. DESIGN/SETTING
      AND PATIENTS:  The study included 44 patients with acromegaly. Pure tone
      audiometry, speech audiometry, tympanometry, otoacoustic emissions testing,
      computerized tomography of the temporal bone and magnetic resonance imaging of
      the ear were performed in all patients. The study also included 36 age- and sex
      matched healthy controls. The patients with acromegaly were divided into three
      subgroups, as follows: controlled disease (n=13); partially controlled disease
      (n=16); uncontrolled disease (n = 15). RESULTS:   In all, 43% of the patients
      with acromegaly had hearing loss, and 20% had had an episode of otitis in at
      least one ear. Median pure tone average (PTA) in the patients with acromegaly was
      12.5 dB (range: 2-72 dB), vs 8.3 dB (range: 0-20 dB) in the control group (P <
      0.001). PTA did not differ significantly between the three patient subgroups.
      Audiometric tests showed various degrees of hearing loss in at least one ear in
      21 patients (48%). Conductive, sensorineural and mixed type hearing loss in at
      least one ear was noted in 9%, 30% and 18% of the patients, respectively.
      Auditory imaging showed that 50% of the patients had temporomandibular joint
      degeneration (TMJD). CONCLUSIONS:   Hearing loss is quite common in patients with
      acromegaly. Contrary to common belief, in this study, conductive hearing loss did
      not occur more frequently than other types. Based on PTA findings in the controls
      and patients with acromegaly, acromegaly caused hearing loss, but the level of
      disease activity had no effect on hearing. Middle ear pressure problems might be
      caused by increased perilymph because of growth hormone (GH)-related volume
      overload.

PMID- 21883348
TI  - Impaired gallbladder motility and the effect of metformin therapy in patients
      with polycystic ovary syndrome.
AB  - OBJECTIVE:   Impaired gallbladder (GB) emptying is a well-documented contributor
      to gallstone formation. The aim of this study was to evaluate GB motility in
      patients with polycystic ovary syndrome (PCOS). METHODS:   The study population
      consisted of 36 PCOS patients and 20 healthy controls. GB volume was calculated
      using the ellipsoid formula (pi/6 * L * D * W) after three-dimensional
      measurements were made by ultrasound [length (L), width (W) and depth (D)].
      Following the determination of fasting GB volume (V0), patients were given a
      standard liquid meal. GB volume measurement was then repeated after 10, 20, 30,
      40, 50, 60, 75 and 90 min. Gallbladder ejection fraction (GBEF) was calculated
      after each measurement. PCOS patients were re-evaluated after a 12-week course of
      metformin therapy at a dose of 1000 mg/day. RESULTS:   Mean baseline GB volume
      (V0) was significantly higher in the patient group compared to the control group
      (27.2 +/- 12.5 cm(3) vs 13.3 +/- 7.0 cm(3) , P < 0.001). While baseline GBEF
      values were similar between groups, increases in GBEF were significantly lower in
      the PCOS group starting from 20 min after consumption of a standard test meal. A
      12-week course of metformin therapy resulted in significant improvements in GB
      volume and GBEF values with a reversal of metabolic and hormonal abnormalities.
      CONCLUSION:   For the first time in the literature, we managed to demonstrate
      impaired GB motility in patients with PCOS. Metformin therapy not only improves
      the metabolic and hormonal imbalances associated with PCOS but also has a
      positive influence on GB motility.

PMID- 21883349
TI  - Drug interactions with mitotane by induction of CYP3A4 metabolism in the clinical
      management of adrenocortical carcinoma.
AB  - Mitotane [1-(2-chlorophenyl)-1-(4-chlorophenyl)-2,2-dichloroethane, (o,p'-DDD)]
      is the only drug approved for the treatment for adrenocortical carcinoma (ACC)
      and has also been used for various forms of glucocorticoid excess. Through still
      largely unknown mechanisms, mitotane inhibits adrenal steroid synthesis and
      adrenocortical cell proliferation. Mitotane increases hepatic metabolism of
      cortisol, and an increased replacement dose of glucocorticoids is standard of
      care during mitotane treatment. Recently, sunitinib, a multityrosine kinase
      inhibitor (TKI), has been found to be rapidly metabolized by CYP3A4 during
      mitotane treatment, indicating clinically relevant drug interactions with
      mitotane. We here summarize the current evidence concerning mitotane-induced
      changes in hepatic monooxygenase expression, list drugs potentially affected by
      mitotane-related CYP3A4 induction and suggest alternatives. For example, using
      standard doses of macrolide antibiotics is unlikely to reach sufficient plasma
      levels, making fluoroquinolones in many cases a superior choice. Similarly,
      statins such as simvastatin are metabolized by CYP3A4, whereas others like
      pravastatin are not. Importantly, in the past, several clinical trials using
      cytotoxic drugs but also targeted therapies in ACC yielded disappointing results.
      This lack of antineoplastic activity may be explained in part by insufficient
      drug exposure owing to enhanced drug metabolism induced by mitotane. Thus,
      induction of CYP3A4 by mitotane needs to be considered in the design of future
      clinical trials in ACC.

PMID- 21883350
TI  - Mother to child transfer of IgG and IgA antibodies against Dermatophagoides
      pteronyssinus.
AB  - There is strong evidence from animal models that placental and/or breast milk
      mediated transfer of maternal allergen-specific IgG prevents allergic immune
      responses in the progeny. Both human and animal data also point to IgA as having
      an important regulatory role. In contrast, little is known about maternal
      transfer of IgG and IgA specific for respiratory allergens in humans.
      Dermatophagoides pteronyssinus (Der p) is an indoor allergen that is a major
      cause of asthma worldwide. We analysed maternal to child Der p-specific IgG and
      IgA transfer in a cohort of 77 paired maternal and child samples. We found Der p
      specific IgG and its IgG1, IgG2 and IgG4 subclasses in all cord blood samples.
      Except for IgG1, cord levels were higher in newborns from atopic mothers (n = 29)
      compared to non-atopic mothers (n = 48). Der p-specific IgA was found in all
      colostrum samples and levels were independent of maternal atopic status. Notably,
      anti-Der p IgG was also found in colostrum and levels were higher in atopic
      mothers. We believe that our work is a critical first step in the identification
      of early factors that may impact asthma development and should guide the
      development of clinical studies that assess whether Der p-specific IgG and IgA
      protect children from allergy as demonstrated in animal models.

PMID- 21883351
TI  - Promoter -817C>T variant of B lymphocyte stimulator gene (BLyS) and
      susceptibility to endometriosis-related infertility and idiopathic infertility in
      Brazilian population.
AB  - Many theories have been proposed to explain the development of endometriosis, and
      recently, autoimmune aetiology has been suggested. Besides, it is well known that
      endometriosis, especially the advanced disease, may impair fertility. B
      lymphocyte stimulator (BLyS) is a cytokine produced by macrophages and is
      necessary for normal B cell development. One of the most studied polymorphisms is
      the -817C/T in the promoter region of the gene. We aimed to assess the
      association between endometriosis-related infertility and idiopathic infertility
      and the BLyS -817C/T polymorphism in a Brazilian population. We performed a case
      control study comprising 165 infertile women with endometriosis, 83 with
      idiopathic infertility and 145 fertile and assessed the association with BLys 
      817C/T polymorphism. BLyS -817C/T polymorphism was detected using TaqMan PCR. The
      results were analysed statistically, and a P-value < 0.05 was considered
      significant. The results disclosed similar genotype and allelic frequencies
      between endometriosis-related infertility (P = 0.225) and control group,
      regardless of the disease stage (P = 0.213 and P = 0.462, respectively). However,
      a statistically significant difference was observed regarding idiopathic
      infertile group (P = 0.048) compared with controls. Considering the dominant and
      recessive inheritance models, no significant differences in both endometriosis
      and idiopathic infertility group were found. The genotype frequencies were in
      Hardy-Weinberg equilibrium in all studied groups. The results point to a possible
      association between BLyS -817C/T polymorphism and idiopathic infertility in
      Brazilian population.

PMID- 21883352
TI  - Establishment of recombinant hybrid-IgG/IgA immunoglobulin specific for Shiga
      toxin.
AB  - Shiga toxin 1 produced by enterohaemorrhagic Escherichia coli is an AB(5)  toxin
      that is involved in the life-threatening haemolytic-uraemic syndrome. The B
      subunits (Stx1B) are cell-binding subunits. We previously established mouse
      hybridoma cell line producing IgA and IgG monoclonal antibodies (mAbs) against
      Stx1B. Here, we cloned cDNAs encoding each of the heavy, light and joining (J)
      chains from the hybridoma cell lines by means of the 5' rapid amplification of
      cDNA ends (RACE) PCR method. Upon assignment of the variable regions of the heavy
      and light chains to known germline sequences, we found substantial somatic
      hypermutation in the complementarity-determining regions in both the IgA and IgG
      mAbs. We also established a hybrid-IgG/IgA heavy chain having variable regions of
      the IgG mAb by means of recombinant PCR methods. Upon transient expression of the
      hybrid-IgG/IgA heavy, IgG-associated light and J chains in COS-1 cells, the
      translated dimeric hybrid-IgG/IgA bound to immobilized Stx1B, as revealed on
      ELISA. The production of dimeric hybrid-IgG/IgA was revealed on immunoblot
      analysis. The dimeric hybrid-IgG/IgA inhibited the binding of digoxigenin
      conjugated Stx1B to natural ligands (CD77) displayed on Burkitt's lymphoma cell
      line Ramos. These results indicate that the replacement of variable regions
      resulted in the production of more useful recombinant dimeric IgA against Stx1B.

PMID- 21883353
TI  - The mild inflammatory response in febrile neutropenic lymphoma patients with low
      risk of complications is more pronounced in patients receiving tobramycin once
      daily compared with three times daily.
AB  - We evaluated inflammatory markers in febrile neutropenic lymphoma patients
      undergoing high-dose chemotherapy with autologous stem cell support. Based on
      MASCC scores, our patients had a low risk of serious complications and a
      perspective of a benign initial clinical course of the febrile neutropenia. We
      also studied the impact of tobramycin given once versus three times daily on
      these immune markers. Sixty-one patients participating in a Norwegian multicentre
      prospective randomized clinical trial, comparing tobramycin once daily versus
      three times daily, given with penicillin G to febrile neutropenic patients,
      constituted a clinically homogenous group. Four patients had bacteraemia, all
      isolates being Gram-positive. Thirty-two patients received tobramycin once daily,
      and 29 patients received tobramycin three times daily. Blood samples were taken
      at the onset of febrile neutropenia and 1-2 days later. All samples were frozen
      at -70  degrees C and analysed at the end of the clinical trial for C-reactive
      protein (CRP), procalcitonin (PCT), complement activation products, mannose
      binding lectin (MBL) and 17 cytokines. We found a mild proinflammatory response
      in this series of patients. CRP was non-specifically elevated. Ten patients with
      decreased MBL levels showed the same mild clinical and proinflammatory response.
      Patients receiving tobramycin once daily showed a more pronounced proinflammatory
      response compared with patients receiving tobramycin three times daily. Overall,
      febrile neutropenic cancer patients with a benign clinical course show a mild
      proinflammatory immune response.

PMID- 21883354
TI  - The influence of dental attendance on change in oral health-related quality of
      life.
AB  - BACKGROUND: Few longitudinal studies have investigated the association between
      dental attendance and oral health-related quality of life (OHRQoL). These studies
      were limited to older adults, or to study participants with an oral disadvantage
      and did not assess if dental attendance had a different effect on OHRQoL for
      different people. OBJECTIVE: This project was designed to test whether routine
      dental attendance improved the OHRQoL of survey participants and whether any
      patient factors influenced the effect of dental attendance on change in OHRQoL.
      METHODS: Collection instruments of a service use log book and a 12 month follow
      up mail self-complete questionnaire were added to the Tasmanian component of the
      National Survey of Adult Oral Health 2004/06. The dependent variable was change
      in OHIP-14 severity and the independent variable was dental attendance. Many
      putative confounders/effect modifiers were analysed in bivariate, stratified and
      three-model multivariate analyses. These included indicators of treatment need,
      sociodemographic characteristics, socioeconomic status, pattern of dental
      attendance and access to dental care. RESULTS: None of the putative confounders
      were associated with both dental attendance and the change in mean OHIP-14
      severity. The only statistically significant interaction for change in OHIP-14
      severity was observed for dental attendance by residential location (P < 0.01).
      In multivariate analysis, there was a statistically significant association of
      dental attendance with change in mean OHIP-14 severity. It also showed that the
      difference in association of attendance between Hobart, the capital city of
      Tasmania, and other places was statistically significant based on the interaction
      between residential location and attendance (P < 0.05). CONCLUSION: The effect of
      dental attendance on OHRQoL was influenced by a patient's residential location.

PMID- 21883355
TI  - Impact of clinical status and salivary conditions on xerostomia and oral health
      related quality of life of adolescents with type 1 diabetes mellitus.
AB  - OBJECTIVES: To investigate the influence of clinical status and salivary
      conditions on the presence of xerostomia on adolescents with and without type 1
      diabetes mellitus (DM1), and further to investigate the influence of clinical
      status, salivary conditions and xerostomia on oral health-related quality of life
      (OHQoL) of those with DM1. METHODS: A cross-sectional study was performed on 102
      adolescents, 51 with DM1 and 51 nondiabetics. Xerostomia was detected by asking a
      question about the sensation of having 'dry mouth', and Oral Health Impact
      Profile-14 was used to measure the impact of xerostomia on OHQoL. The clinical
      status was assessed by using decayed, missing or filled and Community Periodontal
      indices, and by evaluating oral manifestations; and the following salivary
      conditions were evaluated: stimulated salivary flow, pH, buffer capacity, total
      protein, amylase, urea, calcium, and glucose salivary concentrations. Multiple
      logistic regression analysis was used to evaluate the influence of clinical
      status and salivary conditions on xerostomia and the impact of xerostomia on the
      OHQoL of adolescents with DM1. RESULTS: Clinical status and salivary conditions
      was shown to have no influence on the presence of xerostomia. Bivariate (P =
      0.00) and logistic regression (P = 0.01) analysis showed a significant
      association between DM1 and xerostomia. Logistic regression analysis showed
      association between xerostomia (P = 0.00) and OHQoL, and caries experience (P =
      0.03) and OHQoL. CONCLUSIONS: DM1 showed to be predictive of a high prevalence of
      xerostomia in adolescents. Caries experience and xerostomia showed to have a
      negative impact on the OHQoL of adolescents with DM1.

PMID- 21883356
TI  - The association between depression and anxiety and use of oral health services
      and tooth loss.
AB  - OBJECTIVE: The purpose of this study is to examine the associations among
      depression, anxiety, use of oral health services, and tooth loss. METHODS: Data
      were analysed for 80 486 noninstitutionalized adults in 16 states who
      participated in the 2008 Behavioral Risk Factor Surveillance System. Binomial and
      multinomial logistic regression analyses were used to estimate predicted
      marginals, adjusted prevalence ratios, adjusted odds ratios (AOR) and their 95%
      confidence intervals (CI). RESULTS: The unadjusted prevalence for use of oral
      health services in the past year was 73.1% [standard error (SE), 0.3%]. The
      unadjusted prevalence by level of tooth loss was 56.1% (SE, 0.4%) for no tooth
      loss, 29.6% (SE, 0.3%) for 1-5 missing teeth, 9.7% (SE, 0.2%) for 6-31 missing
      teeth and 4.6% (SE, 0.1%) for total tooth loss. Adults with current depression
      had a significantly higher prevalence of nonuse of oral health services in the
      past year than those without this disorder (P < 0.001), after adjustment for age,
      sex, race/ethnicity, education, marital status, employment status, adverse health
      behaviours, chronic conditions, body mass index, assistive technology use and
      perceived social support. In logistic regression analyses employing tooth loss as
      a dichotomous outcome (0 versus >=1) and as a nominal outcome (0 versus 1-5, 6
      31, or all), adults with depression and anxiety were more likely to have tooth
      loss. Adults with current depression, lifetime diagnosed depression and lifetime
      diagnosed anxiety were significantly more likely to have had at least one tooth
      removed than those without each of these disorders (P < 0.001 for all), after
      fully adjusting for evaluated confounders (including use of oral health
      services). The adjusted odds of being in the 1-5 teeth removed, 6-31 teeth
      removed, or all teeth removed categories versus 0 teeth removed category were
      increased for adults with current depression versus those without (AOR = 1.35;
      95% CI = 1.14-1.59; AOR = 1.83; 95% CI = 1.51-2.22; and AOR = 1.44; 95% CI = 1.11
      1.86, respectively). The adjusted odds of being in the 1-5 teeth removed and 6-31
      teeth removed categories versus 0 teeth removed category were also increased for
      adults with lifetime diagnosed depression or anxiety versus those without each of
      these disorders. CONCLUSIONS: Use of oral health services and tooth loss was
      associated with depression and anxiety after controlling for multiple
      confounders.

PMID- 21883357
TI  - Racial disparities in being recommended to surgery for oral and oropharyngeal
      cancer in the United States.
AB  - OBJECTIVES: To investigate the impact of race on the likelihood of patients being
      recommended for surgery after a diagnosis of oral and oropharyngeal cancer.
      METHODS: A total of 68,445 cases of oral and oropharyngeal cancer were extracted
      from the 1988 to 2005 Surveillance, Epidemiology, and End Results (SEER)
      database. County-level rurality data and income data were merged using the US
      Department of Agriculture Rural-Urban Continuum Codes dataset and US Census
      Bureau Small Area Income & Poverty Estimates dataset. We used logistic regression
      analyses to investigate the impact of race on being recommended to surgery for
      oral and oropharyngeal cancer, adjusting for demographic, socioeconomic, and
      clinical factors. Stratified analyses were further conducted by tumor site and
      rural/urban status. RESULTS: Recommendation to surgery varied significantly by
      race, with black patients less likely than white patients to be recommended to
      surgery for their oral and oropharyngeal cancer. The racial difference in
      recommendation to surgery varied significantly by age, geography, and tumor
      subsite. Racial disparities are most evident in lip and buccal cancer from rural
      areas (OR, 4.4; 95% CI, 2.6-7.5); and least evident in oropharyngeal cancer from
      urban areas (OR, 1.2; 95% CI, 1.1-1.3). The magnitude of the racial disparity is
      attenuated with increasing age. CONCLUSIONS: We observed substantial racial
      disparities in surgery recommendation for oral and oropharyngeal cancer in the
      United States. Our results suggest the need to improve accessibility to better
      health care in racial minority groups, particularly in rural areas, and call for
      individual and institutional efforts to avoid physician bias related to the
      patient's sociodemographic characteristics in healthcare service.

PMID- 21883358
TI  - Surgical therapy of advanced ligature-induced peri-implantitis defects: cone-beam
      computed tomographic and histological analysis.
AB  - OBJECTIVES: To evaluate radiological bone level (RBL) (i.e. cone-beam computed
      tomography) and histological bone levels (HBL) as well as re-osseointegration
      [bone-to-implant contact (BIC)] after surgical resective (i.e. implantoplasty)
      and/or regenerative therapy of advanced ligature-induced peri-implantitis in
      dogs. MATERIAL AND METHODS: At all defect sites (n=6 dogs, n=48 implants), the
      intrabony component was filled with a particulate bovine-derived natural bone
      mineral (NBM). The supracrestal component was treated by either the application
      of an equine bone block (EB) or implantoplasty. In a split-mouth design, NBM and
      EB were soak-loaded with recombinant human bone morphogenetic protein (rhBMP)-2
      or sterile saline. All sites were covered by a native collagen membrane and left
      to heal in a submerged position for 12 weeks. RESULTS: A premature wound exposure
      was observed at nine defect sites. Mean RBL and HBL values were lowest in the
      P+rhBMP-2 group, reaching statistical significance when compared with the EB
      group. Mean BIC values were comparable in all groups. Within-group comparisons
      commonly revealed a close correlation between RBL and HBL values. CONCLUSIONS: It
      was concluded that (i) in all groups the investigations failed to predictably
      obtain complete defect resolution, (ii) the surgical procedure was associated
      with high exposure rates, and (iii) RBL was closely correlated with HBL.

PMID- 21883359
TI  - IL-23-producing CD68(+) macrophage-like cells predominate within an IL-17
      polarized infiltrate in chronic periodontitis lesions.
AB  - AIM: To analyse antigen-presenting cells (APCs), such as dendritic cells (DCs),
      macrophages (Mo) or B cells depending on the regional site of chronic
      periodontitis (CP), and to investigate their relation to Th17 cells. MATERIAL AND
      METHODS: Biopsies from oral mucosa as well as the coronal and bottom regions of
      CP were analysed by immunhistochemistry, immunofluorescence, flow cytometry and
      real-time PCR. RESULTS: A predominance of CD68(+) Mo-like cells and CD20(+) B
      cells and strong Th17 infiltration was observed in the bottom region of CP
      lesions, while CD1a(+) DCs were only detected in the coronal regions, where Th17
      infiltration was low. Furthermore, CD68(+) Mo-like cells displayed CD163
      expression as a typical Mo-marker, but expressed in parallel typical DCs markers,
      such as CD11c or CD209 and TLR4. Interestingly, Th17-inducing cytokine IL-23p19
      was produced by CD68(+) Mo-like cells, but not CD20(+) B cells. Moreover, the
      stimulation of in vitro generated CD68(+) Mo-like cells by Porphyromonas
      gingivalis-derived (Pg) lipopolysaccharide resulted in the upregulation of their
      IL-23p19 mRNA expression, which was inhibited by the blockage of TLR4.
      CONCLUSIONS: In view of these data, a picture emerges that IL-17-producing cells
      in CP could be in part directed by CD68(+) Mo-like cells, which produce IL-23p19
      upon TLR4 activation by Pg.

PMID- 21883360
TI  - Oxidative and inflammatory status in Type 2 diabetes patients with periodontitis.
AB  - AIM: To determine the impact of periodontitis on oxidative/inflammatory status
      and diabetes control in Type 2 diabetes. MATERIALS AND METHODS: A comparative
      study of 20 Type 2 diabetes patients with periodontitis [body mass index (BMI)
      31+5], 20-age/gender-matched, non-periodontitis Type 2 diabetes controls (BMI
      29+6) and 20 non-diabetes periodontitis controls (BMI 25+4) had periodontal
      examinations and fasting blood samples collected. Oxidative stress was determined
      by plasma small molecule antioxidant capacity (pSMAC) and protein carbonyl
      levels; inflammatory status by total/differential leucocytes, fibrinogen and high
      sensitivity C-reactive protein (hsCRP); diabetes status by fasting glucose,
      HbA1c, lipid profile, insulin resistance and secretion. Statistical analysis was
      performed using SPSS. RESULTS: pSMAC was lower (p=0.03) and protein carbonyls
      higher (p=0.007) in Type 2 diabetes patients with periodontitis compared with
      those without periodontitis. Periodontitis was associated with significantly
      higher HbA1c (p=0.002) and fasting glucose levels (p=0.04) and with lower beta
      cell function (HOMA-beta; p=0.01) in diabetes patients. Periodontitis had little
      effect on inflammatory markers or lipid profiles, but Type 2 diabetes patients
      with periodontitis had higher levels of hsCRP than those without diabetes
      (p=0.004) and the lowest levels of HDL-cholesterol of all groups. CONCLUSION:
      Periodontitis is associated with increased oxidative stress and compromised
      glycaemic control in Type 2 diabetes patients.

PMID- 21883361
TI  - Cyclosporine-induced gingival overgrowth correlates with NFAT-regulated gene
      expression: a pilot study.
AB  - OBJECTIVE: To determine whether incidence and severity of cyclosporine A (CsA)
      induced gingival overgrowth (GO) is related to expression nuclear factor of
      activated T cells-regulated genes (NFAT-regulated genes). MATERIAL AND METHODS:
      Expression of NFAT-regulated genes was determined in 36 transplant patients
      medicated with CsA by real-time PCR before and 2 h after drug intake and residual
      NFAT activity was estimated as ratio of both measurements. Demographic,
      periodontal and pharmacologic parameters were recorded and GO assessed from
      models. Subjects were divided into two groups according to the degree of GO
      (responders: GO score>=10%). Groups were compared using parametric and non
      parametric tests. The association of various CsA-specific and periodontal
      parameters on incidence and extent of GO were determined using regression
      analysis. RESULTS: Responders had a more than twofold lower residual NFAT
      activity than non-responders (7.9% and 18.1%, respectively; p<0.001). Multiple
      regression analysis revealed gingival inflammation, salivary CsA concentration,
      and residual NFAT activity to be significant factors influencing the expression
      of GO. Seventy-seven percent of the variability of GO could be explained by these
      parameters. CONCLUSIONS: This study showed that pharmacodynamic parameters such
      as residual NFAT activity may be promising prognostic indicators to identify
      patients with increased risk for GO.

PMID- 21883362
TI  - Rapid onset of argyria induced by a silver-containing dietary supplement.
AB  - We describe a 53-year-old man in good general health who presented with an 8
      month history of progressive gray hyperpigmentation of the face. He denied using
      any prescription medications; however, he admitted to taking a herbal supplement.
      Clinically, the differential diagnosis included hemochromatosis, Wilson's disease
      and hyperpigmentation secondary to supplement use. Punch biopsies from the left
      forehead and preauricular region showed heavily sun-damaged skin with a minimal
      inflammatory infiltrate. Closer inspection, however, revealed minute scattered
      black/brown particles distributed in the basement membrane zone of eccrine and
      sebaceous glands. Similar particles were also present in hair follicles, blood
      vessels and arrector pili muscles. The particles did not stain with Gomori
      methenamine silver, Fontana-Masson or iron stains. Electron microscopy with
      energy-dispersive x-ray analysis showed numerous particles, less than 1 um in
      greatest dimension, which showed peaks for silver and sulfur. This analytical
      result confirmed the impression of argyria. Further history revealed that the
      patient had indeed been taking a silver supplement for several months under the
      premise that it would boost his immune system. This case is unique in that the
      patient's hyperpigmentation developed in a short period of time as compared with
      other reports in the medical literature.

PMID- 21883363
TI  - Cutaneous involvement by colonic extranodal NK/T-cell lymphoma mimicking mycosis
      fungoides: a case report*.
AB  - We report a 51-year-old woman with cutaneous involvement by extranodal NK/T-cell
      lymphoma (TCL) of the colon that microscopically mimicked mycosis fungoides (MF).
      She had a history of fever of unknown origin for 2 months and then developed
      multiple erythematous papules on her trunk and extremities. A skin biopsy
      revealed superficial infiltration by atypical small to medium-sized lymphocytes
      with epidermotropism and Pautrier collections. Immunohistochemical studies showed
      expression of CD3 and TIA-1 with lack of expression (double negative) of CD4 and
      CD8. Initially, we reported the diagnosis as MF, cytotoxic variant. Thereafter,
      computerized tomography scan incidentally identified a colonic mass. A colonic
      biopsy revealed infiltration of atypical lymphoid cells with the same morphology
      and immunophenotype as those found in the skin. Additionally, CD56 and Epstein
      Barr virus-encoded RNA in situ hybridization in both skin and colonic biopsies
      were diffusely positive. Thus, extranodal NK/TCL was diagnosed. Delta T-cell
      receptor (TCR) gene rearrangement was documented in the skin biopsy by
      polyacrylamide gel electrophoresis and fluorescence capillary gel electrophoresis
      methods. There was no TCR gene rearrangement detected in the colonic biopsy.
      Unfortunately, the patient died within 2 months of diagnosis.

PMID- 21883364
TI  - An isolated Merkel cell carcinoma metastasis at a distant cutaneous site
      presenting as a second 'primary' tumor.
AB  - Merkel cell carcinoma (MCC) is an aggressive neuroendocrine carcinoma of the
      skin. Disease progression usually occurs via lymphatic spread to regional
      lymphatic draining basins, followed by distant metastasis. We report the clinical
      course, histopathology and genetic analysis of a 69-year-old woman with likely
      hematogenous spread of cutaneous neuroendocrine carcinoma manifesting as a single
      metastatic lesion to a distant cutaneous site. Although the possibility of two
      cutaneous primary MCCs was considered, array comparative genomic hybridization
      (aCGH) identified identical distal amplification of a region of chromosome 12p,
      and synchronous loss of chromosomes 8p and 17p, effectively ruling out the
      possibility of independent primaries. We propose that this represents a primary
      cheek MCC with rapid, isolated cutaneous metastasis to the contralateral ankle
      via hematogenous spread. The distinction between a second primary MCC and a
      distant cutaneous metastasis clearly has important implications with regard to
      staging, treatment and prognosis. To our knowledge, this represents the first
      report of the use of aCGH to clarify the relationship of multiple synchronous
      cutaneous MCCs and the first report of a single distant cutaneous focus of
      hematogenous spread. Our data calls into question prior reports alleging multiple
      cutaneous primaries of this very rare tumor.

PMID- 21883365
TI  - Erythema elevatum diutinum - a chronic leukocytoclastic vasculitis
      microscopically indistinguishable from granuloma faciale?
AB  - BACKGROUND: As the sequential inflammatory changes are the same in erythema
      elevatum diutinum (EED) and granuloma faciale (GF), histopathologic distinction
      may be difficult. METHODS: All available cases from 1998 to 2009 with the
      diagnosis of EED and GF were collected and reviewed, both clinically and
      histopathologically. Nine cases of EED and 41 cases of GF were reviewed in a
      blinded fashion using a checklist of 26 histopathologic criteria. RESULTS: Only
      four of the evaluated criteria showed differences between GF and EED. High
      density of the infiltrate was noted in 97% of cases of GF but only in 56% of
      cases of EED. Eosinophils were the predominant cell type in 59% of cases of GF
      but in none of the cases of EED. Plasma cells were more frequent in GF (64%) than
      in EED (22%), and granulomas were never found in GF but in 22% of EED. A zone of
      perijunctional sparing (Grenz zone) was observed in about three quarters of the
      cases in both the groups. CONCLUSIONS: The histopathology of GF and EED is very
      similar and overlapping. The presence of a Grenz zone and patterned fibrosis does
      not distinguish the two diseases. However, granulomatous nodules are only seen in
      EED, and a predominance of eosinophils in the infiltrate favors a diagnosis of
      GF.

PMID- 21883367
TI  - Human polyomaviruses 6 and 7 are not detectable in Merkel cell polyomavirus
      negative Merkel cell carcinoma.
AB  - BACKGROUND: Merkel cell carcinoma (MCC) has a high degree of association with
      Merkel cell polyomavirus (MCPyV). However, no reliable microscopic, clinical,
      phenotypic or molecular differences have been identified that distinguish MCPyV
      positive from MCPyV-negative MCC, raising the possibility that a related
      polyomavirus may be present in MCPyV-negative cases. Recently, two additional
      human polyomaviruses, human polyomaviruses 6 and 7 (HPyV6 and HPyV7), were shown
      to be present in normal skin of healthy subjects along with MCPyV. Consequently,
      we sought to determine if the presence of HPyV6 of HPyV7 could account for MCPyV
      negative MCC. METHODS: DNA was extracted from formalin-fixed, paraffin-embedded
      tissue blocks of 28 previously characterized MCC cases that included 22 MCPyV
      positive and 6 MCPyV-negative samples. Real-time polymerase chain reaction
      targeting three viral regions was used to detect HPyV6 and HPyV7. RESULTS: None
      of the 28 MCC cases, which included both MCPyV-positive and negative cases,
      showed amplifiable HPyV6 or HPyV7 DNA. CONCLUSIONS: While MCPyV, HPyV6, and HPyV7
      are part of normal skin flora and show a high degree of sequence similarity,
      there is no evidence of an association between HPyV6 and HPyV7 and MCC in this
      case series. This result argues against a role for HPyV6 and HPyV7 in the
      pathogenesis of MCPyV-negative MCC.

PMID- 21883366
TI  - A quantitative proteomic analysis of FFPE melanoma.

PMID- 21883368
TI  - The role of CD10 in distinguishing atypical fibroxanthoma from sarcomatoid
      (spindle cell) squamous cell carcinoma.
AB  - BACKGROUND: The role of CD10 needs clarification in a broader immunohistochemical
      battery for distinguishing atypical fibroxanthoma (AFX) from spindle cell
      squamous cell carcinoma (sSCC). METHODS: We retrospectively reviewed 23 cutaneous
      spindle cell tumors previously classified as AFX (n = 11) or as sSCC (n = 12).
      Each tumor was stained with CD10, S-100, p63 and two or more cytokeratin stains.
      Defining AFX as a diagnosis of exclusion based on multiple negative cytokeratin
      stains and negative p63 staining, we reclassified four squamous cell carcinomas
      (SCCs) as AFX. CD10 staining was reviewed and graded in all tumors. RESULTS:
      Fifteen tumors were classified as AFX. Strongly positive CD10 staining was
      observed in all 15 AFXs, as well as four (50%) of the eight SCCs. Expression of
      p63 was seen in six sSCCs (75%). CONCLUSIONS: CD10 is consistently expressed by
      AFX. However, CD10 is also often strongly expressed by sSCC. Positive staining
      with p63 favors a diagnosis of sSCC. An immunohistochemical battery useful for
      distinguishing AFX from sSCC may include CD10, p63 and two cytokeratin markers.
      However, CD10 alone should not be relied upon in the distinction of these
      entities.

PMID- 21883369
TI  - Histiocytic sarcoma transdifferentiated from follicular lymphoma presenting as a
      cutaneous tumor.
AB  - Histiocytic sarcoma represents a rare and poorly understood tumor of
      histiocytic/dendritic cell lineage that can rarely present in the skin.
      Previously reported cases of histiocytic sarcoma after follicular lymphoma
      suggested that follicular lymphoma can transdifferentiate into histiocytic
      sarcoma. We describe another case involving a 40-year old male who developed
      histiocytic sarcoma in his right thigh 4 years after the diagnosis of grade 1
      follicular lymphoma in the left neck. The two neoplasms were morphologically and
      immunophenotypically different but had identical immunoglobulin heavy chain gene
      and bcl-2 gene rearrangements, as demonstrated by polymerase chain gene reaction
      analysis, and the presence of t(14;18)(q32;q21) translocation was confirmed via
      fluorescence in situ hybridization (FISH) analysis. Because of spindle cell
      morphology and focal S-100 positivity, malignant peripheral nerve sheath tumor
      and melanoma diagnoses were made initially and extensive workup was required to
      discover the correct diagnosis. Lineage transdifferentiation can occur in mature
      lymphoid neoplasms and awareness of this phenomenon and appropriate workup is
      crucial for correct diagnosis, as different treatment protocols and prognosis may
      vary.

PMID- 21883370
TI  - Atypical fibroxanthoma with T-cytotoxic inflammatory infiltrate and aberrant
      expression of cytokeratin.

PMID- 21883371
TI  - Cutaneous accumulation of plasmacytoid dendritic cells associated with acute
      myeloid leukemia: a rare condition distinct from blastic plasmacytoid dendritic
      cell neoplasm.
AB  - A cutaneous infiltrate composed of plasmacytoid dendritic cells may occasionally
      occur in a patient suffering from a myeloid neoplasm. To date, the clinical and
      pathological features associated with this event remains poorly characterized.
      Herein, we report a patient with acute myeloid leukemia who developed pruritic
      papules or erythematous plaques scattered on the skin. Microscopic examination
      showed a dermal infiltrate rich in plasmacytoid dendritic cells expressing CD4,
      CD43, CD68, granzyme B, CD123, CD303 [blood dendritic cell antigen 2 (BDCA-2)],
      CD2-associated protein (CD2AP) and T-cell leukemia/lymphoma oncogene 1 (TCL1).
      Our observation illustrates further that cutaneous lesions associated with some
      myeloid neoplasms, especially those featuring a monocytic component, may be
      composed of plasmacytoid dendritic cells. Because of differences in clinical,
      pathological and genetic features, this rare condition should be distinguished
      from blastic plasmacytoid dendritic cell neoplasm.

PMID- 21883372
TI  - Melanoma and melanocytic nevi in decorative tattoos: three case reports.
AB  - BACKGROUND: In response to the demands of style and fashion, the number of
      decorative tattoos has been increasing worldwide. This has been paralleled by a
      rising incidence of melanocytic proliferations, including melanoma. The
      coincidence of various dermatological diseases and skin tumors with tattoos has
      been documented with some frequency, but reports of melanoma associated with
      tattoos are exceedingly rare. To date, only 13 cases have been documented in the
      English language literature. The possibility of an association between
      melanocytic proliferations and tattoos remains an area for further study.
      OBSERVATIONS: This report presents two cases of melanocytic nevi and one of
      melanoma occurring in association with a decorative tattoos. CONCLUSIONS: At
      present, the pathogenesis of melanoma developing in a tattoo is unknown. Mere
      coincidence cannot be ruled out. However, trauma, ultraviolet light exposure, a
      photoallergic effect, or an inflammatory reaction may promote malignant
      transformation. Clinicians and histopathologists should be aware of the clinical
      and pathological features if they are to make a correct diagnosis.

PMID- 21883373
TI  - Lack of Jun-N-terminal kinase 3 (JNK3) does not protect against neurodegeneration
      induced by 3-nitropropionic acid.
AB  - AIMS: 3-Nitropropionic acid (3-NP) is a toxin that replicates most of the
      clinical and pathophysiological symptoms of Huntington's disease, inducing
      neurodegeneration in the striatum due to the inhibition of mitochondrial
      succinate dehydrogenase. Different pathways have been implicated in the cell
      death induced by 3-NP in rodents. One of them is the Jun-N-terminal kinase (JNK)
      pathway, which may play a role in the neurodegenerative process in different
      diseases. Moreover, the lack of one isoform of JNK (JNK3) has been associated
      with neuroprotection in different experimental models of neurodegeneration.
      Therefore, in the present study the role of JNK3 in the experimental Huntington's
      model induced by 3-NP administration was evaluated. METHODS: 3-NP was
      intraperitoneally administered once a day for 3 days to wild-type and Jnk3-null
      mice. Coronal brain sections were used to determine cell death and astrogliosis
      in striatum. Western blots were performed to determine the involvement of
      different pathways in both wild-type and Jnk3-null mice. RESULTS: Although JNK
      activation was observed following 3-NP administration, the results indicate that
      the lack of JNK3 does not confer neuroprotection against 3-NP toxicity. Thus,
      other pathways must be involved in the neurodegeneration induced in this model.
      One of the possible pathways towards 3-NP-induced apoptosis could involve the
      calpains, as their activity was increased in wild-type and Jnk3-null mice.
      CONCLUSION: Although JNK3 is a key protein involved in cell death in different
      neurodegenerative diseases, the present study demonstrates that the lack of JNK3
      does not confer neuroprotection against 3-NP-induced neuronal death.

PMID- 21883375
TI  - Atypical tauopathy in a patient with LRRK2-G2019S mutation and tremor-dominant
      Parkinsonism.

PMID- 21883376
TI  - FUS immunoreactivity of neuronal and glial intranuclear inclusions in
      intranuclear inclusion body disease.
AB  - AIMS: Recent studies have shown that fused-in-sarcoma (FUS) protein is a
      component of 'neuronal' intranuclear inclusion bodies (INIBs) in the brains of
      patients with intranuclear inclusion body disease (INIBD). However, the extent
      and frequency of FUS-immunoreactive structures in INIBD are uncertain. METHODS:
      We immunohistochemically examined the brain, spinal cord and peripheral ganglia
      from five patients with INIBD and five control subjects, using anti-FUS
      antibodies. RESULTS: In controls, the nuclei of both neurones and glial cells
      were intensely immunolabelled with anti-FUS and neuronal cytoplasm was weakly
      positive for FUS. In INIBD, neuronal and glial INIBs in the brain and spinal cord
      were positive for FUS. FUS-positive INIBs were also found in the peripheral
      ganglia. The proportion of FUS-positive neuronal INIBs relative to the total
      number of inclusion-bearing neurones ranged from 55.6% to 83.3% (average 73.2%)
      and that of FUS-positive glial INIBs ranged from 45.9% to 85.7% (average 62.7%).
      The nucleus and cytoplasm of inclusion-bearing neurones and glial cells showed no
      FUS immunoreactivity. CONCLUSIONS: These findings suggest that FUS is
      incorporated into INIBs in both neurones and glial cells and that loss of normal
      FUS immunoreactivity may result from reduced protein expression and/or
      sequestration within inclusions.

PMID- 21883374
TI  - Activation status of integrated stress response pathways in neurones and
      astrocytes of HIV-associated neurocognitive disorders (HAND) cortex.
AB  - AIMS: Combined anti-retroviral therapy (cART) has led to a reduction in the
      incidence of HIV-associated dementia (HAD), a severe motor/cognitive disorder
      afflicting HIV(+) patients. However, the prevalence of subtler forms of
      neurocognitive dysfunction, which together with HAD are termed HIV-associated
      neurocognitive disorders (HAND), continues to escalate in the post-cART era. The
      microgliosis, astrogliosis, dendritic damage, and synaptic and neuronal loss
      observed in autopsy cases suggest an underlying neuroinflammatory process, due to
      the neurotoxic factors released by HIV-infected/activated macrophages/microglia
      in the brain, might underlie the pathogenesis of HAND in the post-cART era. These
      factors are known to induce the integrated stress response (ISR) in several
      neurodegenerative diseases; we have previously shown that BiP, an indicator of
      general ISR activation, is upregulated in cortical autopsy tissue from HIV
      infected patients. The ISR is composed of three pathways, each with its own
      initiator protein: PERK, IRE1alpha and ATF6. METHODS: To further elucidate the
      specific ISR pathways activated in the central nervous system of HAND patients,
      we examined the protein levels of several ISR proteins, including ATF6,
      peIF2alpha and ATF4, in cortical tissue from HIV-infected patients. RESULTS: The
      ISR does not respond in an all-or-none fashion in HAND, but rather demonstrates a
      nuanced activation pattern. Specifically, our studies implicate the ATF6 pathway
      of the ISR as a more likely candidate than the PERK pathway for increases in BiP
      levels in astrocytes. CONCLUSION: These findings begin to characterize the nature
      of the ISR response in HAND and provide potential targets for therapeutic
      intervention in this disease.

PMID- 21883377
TI  - Distemper virus encephalitis exerts detrimental effects on hippocampal
      neurogenesis.
AB  - AIMS: Despite knowledge about the impact of brain inflammation on hippocampal
      neurogenesis, data on the influence of virus encephalitis on dentate granule cell
      neurogenesis are so far limited. Canine distemper is considered an interesting
      model of virus encephalitis, which can be associated with a chronic progressing
      disease course and can cause symptomatic seizures. METHODS: To determine the
      impact of canine distemper virus (CDV) infection on hippocampal neurogenesis, we
      compared post-mortem tissue from dogs with infection with and without seizures,
      from epileptic dogs with non-viral aetiology and from dogs without central
      nervous system diseases. RESULTS: The majority of animals with infection and with
      epilepsy of non-viral aetiology exhibited neuronal progenitor numbers below the
      age average in controls. Virus infection with and without seizures significantly
      decreased the mean number of neuronal progenitor cells by 43% and 76% as compared
      to age-matched controls. Ki-67 labelling demonstrated that hippocampal cell
      proliferation was neither affected by infection nor by epilepsy of non-viral
      aetiology. Analysis of CDV infection in cells expressing caspase-3, doublecortin
      or Ki-67 indicated that infection of neuronal progenitor cells is extremely rare
      and suggests that infection might damage non-differentiated progenitor cells,
      hamper neuronal differentiation and promote glial differentiation. A high inter
      individual variance in the number of lectin-reactive microglial cells was evident
      in dogs with distemper infection. Statistical analyses did not reveal a
      correlation between the number of lectin-reactive microglia cells and neuronal
      progenitor cells. CONCLUSIONS: Our data demonstrate that virus encephalitis with
      and without seizures can exert detrimental effects on hippocampal neurogenesis,
      which might contribute to long-term consequences of the disease. The lack of a
      significant impact of distemper virus on Ki-67-labelled cells indicates that the
      infection affected neuronal differentiation and survival of newborn cells rather
      than hippocampal cell proliferation.

PMID- 21883378
TI  - Cell biology of Smad2/3 linker region phosphorylation in vascular smooth muscle.
AB  - The transforming growth factor (TGF)-beta superfamily of ligands regulates a
      diverse set of cellular functions. Transforming growth factor-beta induces its
      biological effects through Type I and Type II transmembrane receptors that have
      serine/threonine kinase activities and weak tyrosine kinase activity. In vascular
      smooth muscle, TGF-beta binds to the TGF-beta Type II receptor (TbetaRII) at the
      cell surface, recruiting the Type I receptor (TbetaRI) to form a heterocomplex.
      Consequently, after phosphorylation and activation of TbetaRI, the transcription
      factors receptor activated (R-) Smad2 and Smad3 are recruited and activated
      through phosphorylation of C terminal residues. Overall, Smad2/3 and co-Smad4
      have similar structures consisting of three regions an N-terminal MH1 domain, a C
      terminal MH2 domain and a central linker region. Phosphorylation of the Smad
      linker region appears to have an important role in the regulation of Smad
      activity and function. The mitogen-activated protein kinase (MAPK) family, CDK2,
      CDK4 and calcium-calmodulin dependent kinase are the main kinases that
      phosphorylate sites in the linker region. The role of the linker region includes
      enabling the formation of Smad homo-oligomers and provision of phosphorylation
      sites for MAPK and other kinases. In some instances, linker region
      phosphorylation regulates the inhibition of the nuclear translocation of Smads.
      In the present review, we describe TGF-beta signalling through Smad2/3 and the
      importance of the linker region in the regulation and expression of genes induced
      by TGF-beta superfamily ligands in the context of vascular smooth muscle.

PMID- 21883379
TI  - Linkage between Twist1 and Bmi1: molecular mechanism of cancer
      metastasis/stemness and clinical implications.
AB  - Cancer metastasis is the major cause of cancer-related death despite significant
      improvements in multimodal cancer therapy. Epithelial-mesenchymal transition
      (EMT), a major mechanism of cancer metastasis, is a process that generates cells
      with stem cell-like properties (cancer stemness). Cancer stemness is a concept
      that describes a minor population of cells (cancer stem cells) residing within a
      tumour that are able to self-renew and are resistant to conventional therapy. The
      mechanisms delineating the generation of cancer stemness and its connection to
      cancer metastasis remain largely unknown. Twist1 is an EMT regulator and
      increased Twist1 expression, which has prognostic significance in various human
      cancers, has been widely reported. Bmi1 is a critical component of polycomb
      repressive complex (PRC) 1, which maintains self-renewal and stemness. Bmi1 is
      frequently overexpressed in different types of human cancers and can induce drug
      resistance (Table 2). Recent studies have shown that Twist1 directly activates
      Bmi1 expression and that these two molecules function together to mediate cancer
      stemness and EMT. These results present a unique mechanism of EMT-induced cancer
      metastasis and stemness. Further investigation of the mechanisms of EMT-mediated
      cancer metastasis and stemness will contribute to the management and treatment of
      metastatic cancers.

PMID- 21883380
TI  - Dalteparin dose-dependently increases ROTEM((r)) thrombelastography parameters
      only at supratherapeutic anti-factor Xa levels: an in vitro study.
AB  - 1. The low molecular weight heparin (LMWH) dalteparin is used, for example, to
      prevent primary venous thromboembolism in patients undergoing surgery or in
      medically ill patients. The anticoagulant activity of dalteparin can be monitored
      by measuring anti-factor Xa levels and activated partial thromboplastin time
      (aPTT); however, aPTT is an unreliable parameter in this case. The aim of the
      present in vitro study was to evaluate the thrombelastograph ROTEM((r)) (Tem
      International, Munich, Germany) with respect to determining the anticoagulant
      activity of dalteparin at therapeutic and supratherapeutic plasma concentrations.
      2. The ROTEM((r)) parameters, namely coagulation time (CT), clot formation time
      (CFT) and maximum clot firmness (MCF), were measured using the reagents EXTEM and
      INTEM (Pentapharm, Munich, Germany) at increasing concentrations of dalteparin
      (0.01-10 MUg/mL, which corresponded to anti-factor Xa levels of 1-1000 U/mL,
      respectively). 3. The mean CT measured using EXTEM was found to increase from
      65.4 +/- 27.9 s at baseline to 173.3 +/- 112.2 s and 332.2 +/- 200.7 s at drug
      concentrations of 1 and 10 MUg/mL, respectively (P < 0.0001 for both). Moreover,
      the mean CFT value (EXTEM) increased from 97.7 +/- 21.5 s at baseline to 187.6 +/
      115.2 s (P = 0.0001) at a drug concentration of 10 MUg/mL, which is greater than
      the therapeutic anti-factor Xa concentrations for LMWH. The results obtained when
      INTEM was used as the reagent were similar to those obtained using EXTEM. 4. In
      conclusion, the results indicate that the thrombelastograph ROTEM((r)) can detect
      the anticoagulant effects of dalteparin only at supratherapeutic levels of anti
      factor Xa.

PMID- 21883382
TI  - Mechanism of alcohol-induced impairment in renal development: Could it be reduced
      by retinoic acid?
AB  - 1. Prenatal alcohol exposure impairs kidney development, resulting in a reduced
      nephron number. However, the mechanism through which alcohol acts to disrupt
      renal development is largely unknown. Retinoic acid (RA) is critically involved
      in kidney development and it has been proposed that a diminished concentration of
      RA is a contributing factor to fetal alcohol syndrome. 2. In the present study we
      proposed that the ethanol-induced inhibition of ureteric branching morphogenesis
      and glomerular development in the cultured rat kidney would be ameliorated by
      coculture with exogenous RA and that examining the expression profile of key
      genes involved in the development of the kidney would provide insights into the
      potential molecular pathways involved. 3. Whole rat metanephroi cultured in the
      presence of exogenous RA (10-20 nmol/L) without ethanol appeared larger and had
      significantly more ureteric branch points, tips and glomeruli than metanephroi
      cultured in control media. Those cultured in the presence of ethanol alone (0.2%)
      had 20% fewer ureteric branch points, tips and glomeruli, which was ameliorated
      by coculture with retinoic acid. 4. Gene expression analysis identified changes
      in the expression of enzymes involved in the metabolism of alcohol in conjunction
      with changes in key regulators of kidney development, including cRET. 5. These
      results demonstrate that the teratogenic effects of alcohol in vitro on kidney
      development resulting in reduced ureteric branching morphogenesis and glomerular
      development can be ameliorated through coculture with RA. These results provide
      the foundation for future research into the mechanism through which alcohol acts
      to disrupt kidney development.

PMID- 21883383
TI  - Introduction: Adipokines and cardiovascular disease.

PMID- 21883381
TI  - Regulation of stem cell differentiation in adipose tissue by chronic
      inflammation.
AB  - 1. Recent studies suggest that a local hypoxic response leads to chronic
      inflammation in the adipose tissue of obese individuals. The adipose tissue
      hypoxia may reflect a compensatory failure in the local vasculature system in
      response to obesity. 2. Studies suggest that inflammation stimulates angiogenesis
      and inhibits adipocyte activities in a feedback manner within the obese adipose
      tissue. Adipose-derived stem cells (ASC) are able to differentiate into multiple
      lineages of progenitor cells for adipocytes, endothelial cells, fibroblasts and
      pericytes. Differentiation of ASC into those progenitors is regulated by the
      adipose tissue microenvironment. 3. As a major factor in the microenvironment,
      inflammation may favour ASC differentiation into endothelial cells through the
      induction of angiogenic factors. At the same time, inflammation inhibits ASC
      differentiation into adipocytes by suppressing peroxisome proliferator-activated
      receptor gamma activity and the insulin signalling pathway. In this context,
      inflammation may serve as a signal mediating the competition between adipocytes
      and endothelial cells for the limited source of ASC. 4. It is a new concept that
      inflammation mediates signals in the competition between adipocytes and
      endothelial cells for the limited ASC in obesity. There is a lot of evidence that
      inflammation promotes endothelial cell differentiation. However, this activity of
      inflammation remains to be established in adipose tissue. The present article
      reviews the literature in support of this conclusion.

PMID- 21883384
TI  - Population pharmacokinetics and pharmacodynamics of escitalopram in overdose and
      the effect of activated charcoal.
AB  - AIMS: To describe the pharmacokinetics and pharmacodynamics (PKPD) of
      escitalopram in overdose and its effect on QT prolongation, including the
      effectiveness of single dose activated charcoal (SDAC). METHODS: The data set
      included 78 escitalopram overdose events (median dose, 140mg [10-560mg]). SDAC
      was administered 1.0 to 2.6 h after 12 overdoses (15%). A fully Bayesian analysis
      was undertaken in WinBUGS 1.4.3, first for a population pharmacokinetic (PK)
      analysis followed by a PKPD analysis. The developed PKPD model was used to
      predict the probability of having an abnormal QT as a surrogate for torsade de
      pointes. RESULTS: A one compartment model with first order input and first-order
      elimination described the PK data, including uncertainty in dose and a baseline
      concentration for patients taking escitalopram therapeutically. SDAC reduced the
      fraction absorbed by 31% and reduced the individual predicted area under the
      curve adjusted for dose (AUC(i) /dose). The absolute QT interval was related to
      the observed heart rate with an estimated individual heart rate correction factor
      (alpha= 0.35). The heart rate corrected QT interval (QT(c) ) was linearly
      dependent on predicted escitalopram concentration [slope = 87ms/(mgl(-1) )],
      using a hypothetical effect-compartment (half-life of effect-delay, 1.0h).
      Administration of SDAC significantly reduced QT prolongation and was shown to
      reduce the risk of having an abnormal QT by approximately 35% for escitalopram
      doses above 200mg. CONCLUSIONS: There was a dose-related lengthening of the QT
      interval that lagged the increase in drug concentration. SDAC resulted in a
      moderate reduction in fraction of escitalopram absorbed and reduced the risk of
      the QT interval being abnormal.

PMID- 21883385
TI  - Pre-hypertension: how low to go and do drugs have a role?
AB  - People with pre-hypertension (high blood pressure but below the conventional
      threshold for intervention with antihypertensive drugs) undoubtedly have
      increased risk of cardiovascular and other complications. However, the vast
      majority has low absolute risk and whether treatment would be beneficial is
      uncertain. While pharmacotherapy has attractions from a public health
      perspective, clinicians and crucially those with pre-hypertension require robust
      evidence that drug treatment will lead to short term as well as long term gains.
      Any changes in recommendations should await adequately powered outcome studies
      which provide solid evidence of the magnitude of absolute risk reduction in
      treating pre-hypertension and assessment of the cost-effectiveness.

PMID- 21883386
TI  - Pharmacokinetic interaction between domperidone and ketoconazole leads to QT
      prolongation in healthy volunteers: a randomized, placebo-controlled, double
      blind, crossover study.
AB  - AIMS: To assess the steady-state pharmacokinetic and QT(c) effects of domperidone
      and ketoconazole, given alone and together. METHODS: A randomized, placebo
      controlled, double-blind, crossover study was carried out. Healthy subjects (14
      men, 10 women; age 18-39 years; mean weight 73.5kg, range 53.8-98.8kg; 23
      Europid, 1 Afro-Caribbean) received orally, for 7 days each, placebo, domperidone
      10mg, four doses daily, at 4h intervals, ketoconazole 200mg 12-hourly and
      domperidone and ketoconazole together. The washout period was 15 days.
      Pharmacokinetics and serial 12-lead ECGs were assessed on day 7, and serial ECGs
      on day -1 and at follow-up. Two subjects withdrew before the third treatment
      period, so data were available for 22-24 subjects. RESULTS Ketoconazole tripled
      domperidone concentrations at steady-state. Domperidone, ketoconazole and their
      combination significantly increased QT(c) F in men. Overall adjusted mean
      differences from placebo were 4.20 (95% CI 0.77, 7.63), 9.24 (95% CI 5.85, 12.63)
      and 15.90 (95% CI 12.47, 19.33) ms, respectively. In women, QT(c) F was not
      significantly different from placebo on either domperidone or ketoconazole alone,
      or in combination. However, QT(c) was positively correlated with plasma drug
      concentrations, in both men and women. DeltaQT(c) F increased by about 2ms per
      10ngml(-1) rise in domperidone concentration, and per 1ugml(-1) rise in
      ketoconazole concentration. CONCLUSIONS: Ketoconazole tripled the plasma
      concentrations of domperidone. Domperidone and ketoconazole increased QT(c) F in
      men, whether given together or separately. The effect of domperidone alone was
      below the level of clinical importance. The negative result in women is
      unexplained.

PMID- 21883387
TI  - Impact of genetic factors (VKORC1, CYP2C9, CYP4F2 and EPHX1) on the
      anticoagulation response to fluindione.
AB  - AIM: Genetic variants of the enzyme that metabolizes warfarin, cytochrome P-450
      2C9 (CYP2C9) and of a key pharmacologic target of vitamin K antagonists, vitamin
      K epoxide reductase (VKORC1), contribute to differences in patients' responses to
      coumarin derivatives. The role of these variants in fluindione response is
      unknown. Our aim was to assess whether genetic factors contribute to the
      variability in the response to fluindione. METHODS: Four hundred sixty-five
      patients with a venous thromboembolic event treated by fluindione for at least 3
      months with a target international normalized ratio (INR) of 2.0 to 3.0 were
      studied. VKORC1, CYP2C9, CYP4F2 and EPHX1 genotypes were assessed. INR checks,
      fluindione doses and bleeding events were collected. RESULTS: VKORC1 genotype had
      a significant impact on early anticoagulation (INR value >=2 after the first two
      intakes) (P < 0.0001), on the time required to reach a first INR within the
      therapeutic range (P < 0.0001) and on the time to obtain a first INR value > 4
      (P= 0.0002). The average daily dose of fluindione during the first period of
      stability was significantly associated with the VKORC1 genotype: 19.8 mg (+/-5.5)
      for VKORC1 CC, 14.7mg (+/-6.2) for VKORC1 CT and 8.2mg (+/-2.5) for VKORC1 TT (P
      < 0.0001). CYP2C9, CYP4F2 and EPHX1 genotypes did not significantly influence the
      response to fluindione. CONCLUSIONS: VKORC1 genotype strongly affected
      anticoagulation induced by fluindione whereas CYP2C9, CYP4F2 and EPHX1 genotypes
      seemed less determining.

PMID- 21883388
TI  - Subcutaneous ossifying lipoma with infiltration of transforming growth factor
      beta-producing cells.

PMID- 21883389
TI  - Coexistent granulomatous vasculitis and leukaemia cutis in a patient with
      resolving herpes zoster.
AB  - An 80-year-old man presented with a 6-month history of indurated tender purple
      papules. These had coalesced to form plaques with some central scarring and a
      dermatomal distribution on the left arm, immediately following herpes zoster (HZ)
      infection at this site. The patient had a 5-year history of small lymphocytic
      lymphoma (SLL), which was being managed conservatively under a 'watch and wait'
      protocol. On histological examination of a skin biopsy, marked interstitial
      granulomas and prominent granulomatous vasculitis were seen, supporting the
      clinical impression of a post-HZ granulomatous reaction. In addition, there was a
      dense monoclonal small B-cell lymphocytic infiltrate indicating koebnerization by
      SLL (a finding that has not been reported previously with concurrent postherpetic
      granulomatous vasculitis). Although benign pseudolymphomas occur in postherpetic
      cases, this case shows that even in association with benign vasculitic features
      true lymphomas can occur. Furthermore, this case highlights the importance of
      immunocytochemistry, molecular studies and clinicopathological correlation.

PMID- 21883390
TI  - Primary cutaneous nocardiosis due to Nocardia vinacea: first case in an
      immunocompetent patient.

PMID- 21883391
TI  - Resolving actinic keratoses: an expected side-effect of capecitabine therapy.

PMID- 21883392
TI  - Digging for gold in a dermatology clinic.

PMID- 21883393
TI  - The nuclear factor kappa B p50 subunit and cortactin as markers to distinguish
      between keratoacanthoma and well-differentiated squamous cell carcinoma.
AB  - BACKGROUND: Distinguishing keratoacanthoma (KA) from well-differentiated squamous
      cell carcinoma (SCC) is sometimes difficult. Recent evidence indicates that the
      nuclear factor kappa B p50 subunit (p50) and cortactin might be useful to
      distinguish between these two conditions. AIM: To verify whether p50 and
      cortactin are useful differentiation markers to distinguish between subungual KA
      and well-differentiated SCC. METHODS: Immunohistochemistry using p50, cortactin
      and Ki-67 was performed on 20 patients with KA and 20 patients with facial well
      differentiated SC. Ki-67 staining was also evaluated and scored. RESULTS: Both
      p50 and cortactin had higher levels of expression in KA than in SCC. Both were
      localized to the basal-cell layer of KA, whereas they were scattered without
      polarity throughout the SCC lesions. Although the Ki-67 index was not
      significantly different between KA and SCC, the staining pattern also showed loss
      of polarity in SCC. CONCLUSION: p50 and cortactin might be useful makers to
      distinguish between KA and well-differentiated SCC.

PMID- 21883394
TI  - Hair shedding in women.

PMID- 21883395
TI  - Ultraviolet B radiation to the eye induces pigmentation in the epidermis via the
      activation of the subunit gp91 phox of reduced nicotinamide adenine dinucleotide
      phosphate oxidase.
AB  - Irradiation by ultraviolet (UV)B is known to increase the number of dopamine
      (Dopa)-positive melanocytes in the skin. In this study, a 2.5-kJ/m(2)  dose of
      UVB radiation was delivered by a sunlamp to the ear or the eye of wild-type
      C57BL/6j mice and of gp91 phox(-/-)  C57BL/6j mice that had a knockout mutation
      of the gp91 phox subunit of reduced nicotinamide adenine dinucleotide phosphate
      oxidase (NADPH). The degree of change in the Dopa-positive melanocyte expression
      in was reduced in gp91 phox(-/-)  mice given UVB irradiation to the eye, but not
      in those given irradiation to the ear. The plasma level of alpha-melanocyte
      stimulating hormone (alpha-MSH) in the blood increased in the C57BL/6j mice after
      irradiation to either the eye or the ear, but it did not increase in the gp91
      phox(-/-)  mice given UVB irradiation to the eye. Both gp91 phox and alpha-MSH in
      the central nervous system seem to contribute to pigmentation after UVB
      irradiation of the eye in mice.

PMID- 21883396
TI  - Intratumoral injection of OK-432 suppresses metastatic squamous cell carcinoma
      lesion inducing interferon-gamma and tumour necrosis factor-alpha.

PMID- 21883397
TI  - Antioxidant status in patients with lichen planus.
AB  - BACKGROUND: Lichen planus (LP) is an autoimmune inflammatory disease of the
      mucocutaneous tissue, whose exact pathological course is not yet understood. Many
      studies have implicated the role of reactive oxygen species (ROS) and the
      protective role of antioxidants in several autoimmune skin disorders. In this
      study, serum levels of antioxidants in patients with LP were determined and
      compared with those of healthy controls. METHODS: In total, 30 patients with LP
      (mean +/- SD age 41.63 +/- 13.03), who had never received treatment for their
      disease, were enrolled; 30 healthy people (aged 41.17 +/- 13.24) were recruited
      as the control group. Serum levels of glutathione peroxidase (GPX), vitamin C,
      selenium, bilirubin and uric acid were determined. RESULTS: The mean plasma level
      of vitamin C was significantly lower (P < 0.001) in patients compared with
      controls. A significant positive correlation was found between selenium and GPX
      in both patients (Spearman rho = 0.99, P < 0.001) and controls (rho = 0.10, P <
      0.001). CONCLUSIONS: Lower serum levels of vitamin C in patients with LP
      indicates that free radicals and the resulting oxidative damage may be important
      in the pathogenesis of LP lesions.

PMID- 21883398
TI  - Analysis of ATP2C1 gene mutations in Chinese patients with Hailey-Hailey disease.

PMID- 21883399
TI  - Analysis of the differentially expressed genes in Microsporum canis in inducing
      smooth skin and scalp tissue conditions.
AB  - Microsporum canis is a common zoophilic dermatophyte, which causes a range of
      infections. To explore the pathogenic mechanism of tinea capitis, we used the
      suppression subtractive hybridization (SSH) technique to investigate the
      differences in gene expression between different cultures of Microsporum canis
      incubated on three different types of mineral media containing child glabrous
      skin, child scalp tissue and adult scalp tissue. Using dot-blot hybridization and
      real-time PCR technique, we successfully screened and identified a pair of genes
      that had expression levels 44.6 and 117 times higher in culture 1 (M. canis
      cultured in mineral medium with child scalp tissue) than in culture 2 (M. canis
      cultured in mineral medium with glabrous skin tissue), and another pair of genes
      with expression levels 78.2 and 9.8 times higher in culture 1 than in culture 3
      (M. canis cultured in mineral medium with adult scalp tissue). These four genes
      were found to have 41%, 53%, 40% and 94% homology to those encoding a
      hypothetical protein [family of serine hydrolases 1; (FSH1)], PQ loop repeat
      protein (PQ-LRP), a predicted protein [porphyrin galactose 4; (P-GAL4)] and NADH
      dehydrogenase subunit (NADH)1, respectively. The upregulation of the FSH1, PQ
      LRP, P-GAL4 and NADH1 genes in cultures of child scalp tissue indicates that they
      are essential in the pathogenesis of tinea capitis caused by M. canis.

PMID- 21883400
TI  - Circulating miR-142-3p levels in patients with systemic sclerosis.
AB  - BACKGROUND: Recently, increased evidence has shown that serum micro (mi)RNA
      levels are a useful biomarker for the diagnosis, prognosis and therapeutic value
      of various diseases. However, serum miRNA has not been investigated in patients
      with systemic sclerosis (SSc), to our knowledge. AIM: To investigate the
      possibility that serum levels of Homo sapiens miR-142 stem-loop (hsa-miR-142-3p),
      one of the miRNAs regulating the expression of integrin alphaV, could be a
      specific disease marker for SSc. METHODS: Serum samples were obtained from 61
      patients with SSc and 20 healthy controls. Patients with systemic lupus
      erythematosus (SLE), dermatomyositis (DM) and scleroderma spectrum disorder
      (SSD), who did not fulfil American College of Rheumatology criteria for SSc but
      might develop SSc in the future, were included as disease controls in this study.
      miRNAs were purified from serum, and miR-142-3p levels were measured with a
      quantitative real-time PCR assay. RESULTS: Serum miR-142-3p levels in patients
      with SSc were significantly higher than in patients with SSD, SLE or DM, and
      healthy control groups. Patients with increased miR-142-3p levels tended to have
      a short sublingual frenulum. CONCLUSIONS: Our data indicate that serum levels of
      miR-142-3p may be elevated specifically in patients with SSc, correlating with
      the severity of this disease, and may be useful diagnostic markers for the
      presence of SSc and for the differentiation of SSc from SSD.

PMID- 21883401
TI  - Granulysin-producing cytotoxic T cells in the mucocutaneous lesions of Behcet
      disease: a distinct inflammatory response from erythema nodosum.
AB  - BACKGROUND: Cytotoxic T lymphocytes (CTLs) have been recognized as an important
      effector cell in Behcet disease (BD). Granulysin is a cytolytic granule protein
      expressed by CTLs and natural killer cells. AIM: To evaluate the involvement of
      granulysin-producing T cells in the pathogenesis of BD. METHODS: Using
      immunohistochemistry, lymphocyte subsets expressing granulysin were investigated
      in mucocutaneous lesions of BD. Serum granulysin levels were assayed by ELISA.
      RESULTS: Granulysin-positive cells were seen in specimens from oral ulcers,
      genital ulcers and acne-like eruptions, but not erythema nodosum-like lesions.
      Both CD4+ and CD8+ T cells expressed granulysin. Serum granulysin levels did not
      correlate with disease activity in BD. CONCLUSION: Immune reactions mediated by
      granulysin-positive CTLs may play an important role in the pathogenesis of acne
      like eruptions, oral ulcers and genital ulcers in BD.

PMID- 21883402
TI  - Epidermotropic CD8+ cytotoxic T-cell lymphoma exhibiting a transition from the
      indolent to the aggressive phase, accompanied by emergence of CD7+ cells and
      formation of neutrophilic pustules.
AB  - A 47-year-old-man presented with rashes on his trunk and limbs, and a diagnosis
      of parapsoriasis was made. Ten years later, the rashes had progressed gradually
      to form plaques and tumours. Gene rearrangement studies revealed monoclonality of
      the T-cell receptor beta-chain (TCR-Jbeta)1 gene, and results of flow cytometry
      and immunohistochemical examination confirmed a diagnosis of epidermotropic CD8+
      cytotoxic T-cell lymphoma. The clinical course of the disease remained indolent
      for some time, but about 2 years later, neutrophilic pustules formed on the
      surface of the skin lesions, and tumours developed in the patient's testes. Using
      flow cytometry, emergence of CD7+ cells was found. The patient died the following
      year of respiratory failure due to brain herniation. On postmortem examination,
      CD8+ tumour cells were found in the brain. This case demonstrates an unusually
      protracted indolent phase in a patient with cutaneous aggressive epidermotropic
      CD8+ cytotoxic T-cell lymphoma; its transition into the aggressive phase was
      accompanied by emergence of CD7+ cells and formation of neutrophilic pustules.

PMID- 21883403
TI  - Academic dismissal policy for medical students: effect on study progress and help
      seeking behaviour.
AB  - CONTEXT: Medical students often fail to finish medical school within the
      designated time. An academic dismissal (AD) policy aims to enforce satisfactory
      progress and to enable early identification and timely support or referral of
      struggling students. In this study, we assessed whether the implementation of an
      AD policy improved study progress in the first 2 years of medical school.
      Additionally, we analysed its effect on the help-seeking behaviour of struggling
      students. METHODS: We compared two AD cohorts (entering in 2005 and 2006,
      respectively) and two non-AD cohorts (entering in 2003 and 2004, respectively) on
      dropout rates, Year 1 curriculum completion rates and the percentage of students
      with an optimal study rate (i.e. all modules completed) at 1 and 2 years after
      enrolment. We also measured the effect on study progress of attending the support
      meetings offered. RESULTS: The AD (n = 809) and non-AD cohorts (n = 809) did not
      differ significantly in dropout rate at 5 months, in Year 1 completion rate at 2
      years and in the percentage of optimally performing students at 1 year after
      enrolment. At 2 years after enrolment, more students from the AD cohorts had left
      and more non-AD students demonstrated optimal performance, but effect sizes (ESs)
      for these differences were small. Voluntary support at 4 months was attended by
      AD students more often than by non-AD students (68.9% versus 39.8%; chi(2) ((1))
      = 43.95, p < 0.001, ES = 0.29). The AD students who attended the support meetings
      completed the Year 1 curriculum more often than those who did not (73.4% versus
      52.5%; chi(2) ((1)) = 10.92, p < 0.001, ES = 0.20). Attending the obligatory
      support meeting at 7 months had a similar effect (70.5% versus 33.3%; chi(2)
      ((1)) = 13.60, p < 0.001, ES = 0.23). CONCLUSIONS: The presence of an AD policy
      did not lead to earlier dropout, higher completion rates or an improved study
      rate during the first 2 years at medical school. However, uptake of the support
      offered increased to almost 70%. Although support participants finished the Year
      1 curriculum more often than non-participants, the current support system was not
      sufficient to improve overall study progress.

PMID- 21883404
TI  - Medical students' experiences of shame in professional enculturation.
AB  - CONTEXT: Despite the intentions of caregivers not to harm, medical encounters may
      involve intimidation and induce emotions of shame. Reflection is a critical part
      of professional learning and training. However, the role of shame in medical
      education has scarcely been studied. The aim of this study was to explore medical
      students' reflections on shame-related experiences in clinical situations and to
      examine how they tackled these experiences. METHODS: A 24-credit course in
      Professional Development is held at the Medical School of Umea University,
      Sweden. A 1-day seminar on the theme of shame, which involves individual
      reflections and group discussions, is held in term 9. Medical students were
      invited to individually consider and write down their memories of situations in
      which they had experienced shame in clinical encounters. Of a total of 133
      students, 75 were willing to share their written reflections anonymously. Their
      essays were transcribed to computer text and analysed by means of qualitative
      content analysis. RESULTS: Three themes emerged. These included: Difficulties in
      disclosing shame; Shame-inducing circumstances, and Avoiding or addressing shame.
      Initially, students experienced problems in recalling shameful incidents, but
      successively described various situations which related to being taken by
      surprise, being exposed, and being associated with staff imprudence. Students
      disclosed shame avoidance behaviours, but also gave examples of how addressing
      shame provided them with new insights and restored their dignity. CONCLUSIONS:
      Students' reflections on shameful experiences elucidated the importance of
      attitudes, manners, standards and hierarchies in clinical situations. These are
      important issues to highlight in the professional enculturation of medical
      students; our emphasising of them may encourage medical teachers elsewhere to
      organise similar activities. Opportunities for mentoring medical students in
      tackling shame and adverse feelings, and in resolving conflict, are needed in
      medical curricula.

PMID- 21883405
TI  - Selected medical students achieve better than lottery-admitted students during
      clerkships.
AB  - OBJECTIVES: A recent controlled study by our group showed that the dropout rate
      in the first 2 years of study of medical students selected for entry by the
      assessment of a combination of non-cognitive and cognitive abilities was 2.6
      times lower than that of a control group of students admitted by lottery. The aim
      of the present study was to compare the performance of these two groups in the
      clinical phase. METHODS: A prospective cohort study was performed to compare the
      performance of 389 medical students admitted by selection with that of 938
      students admitted by weighted lottery between 2001 and 2004. Follow-up of these
      cohorts lasted 5.5-8.5 years. The main outcome measures were the mean grade
      obtained on the first five discipline-specific clerkships by all cohorts and the
      mean grade achieved on all 10 clerkships by the cohorts of 2001 and 2002.
      RESULTS: Selected students obtained a significantly higher mean grade during
      their first five clerkships than lottery-admitted students (mean +/- standard
      error [SE] 7.95 +/- 0.03, 95% confidence interval [CI] 7.90-8.00 versus mean +/-
      SE 7.84 +/- 0.02, 95% CI 7.81-7.87; p < 0.001). This difference reflected the
      fact that selected students achieved a grade of >= 8.0 1.5 times more often than
      lottery-admitted students. An analysis of all mean grades awarded on 10
      clerkships revealed the same results. Moreover, the longer follow-up period over
      the clerkships showed that the relative risk for dropout was twice as low in the
      selected student group as in the lottery-admitted student group. CONCLUSIONS: The
      selected group received significantly higher mean grades on their first five
      clerkships, which could not be attributed to factors other than the selection
      procedure. Although the risk for dropout before the clinical phase increased
      somewhat in both groups, the actual dropout rate proved to be twice as low in the
      selected group.

PMID- 21883406
TI  - A triadic interplay between academics, practitioners and students in the nursing
      theory and practice dialectic.
AB  - AIM:   This article is a report of a descriptive study of the effectiveness of
      classroom teaching by clinical nurse specialists on students' transfer of theory
      into practice. BACKGROUND:   Ongoing concern about a theory-practice merger in
      nursing has led to collaborative initiatives between academics and practitioners
      globally. There are different forms of collaborative efforts, but information on
      their evaluation is scarce and inconclusive. Integration of theory and practice
      is important for an outcome-based approach, which emphasizes students' clinical
      competence as the measure of success. The limited nursing discussion on theory
      and practice collaboration in education was our impetus for the study. METHODS:  
      Between 2007 and 2008, focus group interviews were held, first with 75 and then
      with 35 from the same group of first-year students, regarding their learning
      experience from the lectures of the two clinical nurse specialists in diabetes
      and colostomy care, respectively, prior to and after their clinical placements.
      Six of their clinical instructors and the two clinical nurse specialists were
      also interviewed. The audiotaped interviews were transcribed verbatim and
      analysed using content analysis. FINDINGS:   Three themes were identified: impact
      of students' vicarious learning from clinical nurse specialists' stories of
      experience; improving the collaboration between clinical nurse specialists and
      subject lecturers for junior students' learning experience; continuity in the
      clinical integration of theory-practice as dialectic through an interplay between
      academics, practitioners and students. CONCLUSION:   The theory and practice
      issue is best addressed as a triadic paradigm in a community of practice with the
      collaboration among academics, practitioners and students.

PMID- 21883407
TI  - A comparison of patient and family caregiver prospective control over lung
      cancer.
AB  - AIM:   This paper is a report of our secondary analysis of patient and family
      caregiver prospective control in lung cancer. BACKGROUND:   Control beliefs
      underlie self-care in sickness and health. Self-care often involves 'shared'
      activities between the afflicted individual and caregiving family and friends.
      However, depending on how control is perceived, conflicts can occur in decision
      making thus jeopardizing optimal self-care. We need to comprehend how control
      beliefs compare between patients and caregivers and how their control beliefs are
      linked with dealing with serious illness. METHODS:   Based on questionnaire data
      collected in our larger study between September 2005 and February 2009, we
      conducted exploratory comparative analyses of 304 patients' and caregivers'
      control beliefs in managing lung cancer. Eight 5-point response items captured
      prospective control. Exploratory factor analysis with promax rotation was
      conducted to compare dyadic perceptions on the dimensionality of prospective
      control. We also conducted exploratory correlations between control beliefs and
      smoking cessation, attributional reactions, caregiver helping and symptom
      reports. RESULTS:   Principal component analysis identified the same factors for
      patients and caregivers: factor 1, Fate control and factor 2, Team control.
      Patient and caregiver 'Fate' and 'Team' control sub-scales were respectively
      associated with hope, caregiver helping and patient smoking cessation.
      CONCLUSION:   Clinicians need to support, adapt or develop a philosophy of cancer
      care that is inclusive of partnerships, drawing on beliefs of patients and
      caregivers that controlling lung cancer is a team effort which in turn is
      tentatively linked to patient smoking cessation, positive emotions and caregiver
      helping.

PMID- 21883408
TI  - The relationship between in-hospital mortality, readmission into the intensive
      care nursing unit and/or operating theatre and nurse staffing levels.
AB  - AIM:   The aim of this article was to assess the relationship between (1) in
      hospital mortality and/or (2) unplanned readmission to intensive care units or
      operating theatre and nurse staffing variables. BACKGROUND:   Adverse events are
      used as surrogates for patient safety in nurse staffing and patient safety
      research. A single adverse event cannot adequately capture the multi-dimensional
      attributes of patient safety; hence, there is a need to consider composite
      measures. Unplanned readmission into the postoperative Intensive Care nursing
      unit and/or operating Theatre and in-hospital mortality can be viewed as measures
      that incorporate the effects of several adverse events. METHODS:   We conducted a
      Bayesian multilevel analysis on a subset of the 2003 Belgian Hospital Discharge
      and Nursing Minimum Data sets. The sample included 9054 patients who underwent
      coronary artery bypass surgery or heart valve procedures from 28 Belgian acute
      hospitals. Two proxies of patient safety were considered, namely postoperative in
      hospital mortality in the first postoperative intensive care unit and unplanned
      readmission into the intensive care and/or operating theatre (including mortality
      beyond the first postoperative intensive care unit) after the first-operative
      intensive care nursing unit. RESULTS:   There is an association between in
      hospital mortality and/or unplanned readmissions and nurse staffing levels, but
      the relationship is moderated by volume and severity of illness respectively. In
      addition, the relationship differs between the two endpoints. CONCLUSION:  
      Higher nurse staffing levels on postoperative general nursing cardiac surgery
      units protected patients from unplanned readmission to intensive care units or
      operating theatre and in-hospital mortality.

PMID- 21883410
TI  - History of military service and the risk of suicidal ideation: findings from the
      2008 national survey on drug use and health.
AB  - Studies of completed suicide by history of military service have produced
      inconsistent findings; no representative population-based study has compared the
      risk of nonfatal suicidal behavior among veterans with risk among nonveterans.
      The objective of this study was to examine whether male veterans of the U.S.
      military are at heightened risk of suicidal ideation, compared with males who
      never served in the U.S. military. A total of 17,641 adult men completed the 2008
      National Survey on Drug Use and Health (NSDUH). Subjects provided information
      about history of ever having served in the U.S. armed forces, past suicidal
      ideation, alcohol and drug abuse and dependence, measures of psychological
      distress, and sociodemographic data. Overall, men who had ever served in the
      armed forces were no more likely than men who had never served to report having
      seriously considered suicide over the prior 12 months. Military status was not
      differentially associated with other known suicide risk factors assessed by
      NSDUH, including psychiatric disorders. Our findings suggest that evidence-based
      suicide prevention strategies applicable to the general population should be
      employed to reduce suicide risk among the veteran population as well.

PMID- 21883409
TI  - Alcohol-related problems and risk of suicide among college students: the
      mediating roles of belongingness and burdensomeness.
AB  - The relationship among alcohol-related problems, perceived burdensomeness,
      thwarted belongingness, and suicide proneness in undergraduate college students
      (N=996) was examined. As hypothesized, alcohol-related problems, perceived
      burdensomeness, and thwarted belongingness were all significantly and positively
      correlated with suicide proneness. The relation between experiencing alcohol
      related problems and suicide proneness was, in part, accounted for by perceived
      burdensomeness and thwarted belongingness. Additionally, the mediation via
      perceived burdensomeness was significantly stronger than the mediation via
      thwarted belongingness. Results suggest that it would be advisable for clinicians
      to be aware of students' experiences with alcohol-related problems in conjunction
      with their levels of burdensomeness and belongingness when assessing for suicide
      risk.

PMID- 21883411
TI  - Elevated suicide rates at high altitude: sociodemographic and health issues may
      be to blame.
AB  - Suicide rates are higher at high altitudes; some hypothesize that hypoxia is the
      cause. We examined 8,871 suicides recorded in 2006 in 15 states by the National
      Violent Death Reporting System, with the victim's home county altitude determined
      from the National Elevation Dataset through FIPS code matching. We grouped cases
      by altitude (low<1000m; middle=1000-1999m; high>=2000m). Of reported suicides, 5%
      were at high and 83% at low altitude, but unadjusted suicide rates per 100,000
      population were higher at high (17.7) than at low (5.7) altitude. High and low
      altitude victims differed with respect to race, ethnicity, rural residence,
      intoxication, depressed mood preceding the suicide, firearm use and recent
      financial, job, legal, or interpersonal problems. Even after multivariate
      adjustment, there were significant differences in personal, mental health, and
      suicide characteristics among altitude groups. Compared to low altitude victims,
      high altitude victims had higher odds of having family or friends report of a
      depressed mood preceding the suicide (OR 1.78; 95%CI:1.46-2.17) and having a
      crisis within 2weeks before death (OR 2.00; 95%CI:1.63-1.46). Suicide victims at
      high and low altitudes differ significantly by multiple demographic, psychiatric,
      and suicide characteristics; these factors, rather than hypoxia or altitude
      itself, may explain increased suicide rates at high altitude.

PMID- 21883412
TI  - Analysis of dermatomyositis-specific autoantibodies and clinical characteristics
      in Japanese patients.
AB  - Dermatomyositis (DM) is an idiopathic systemic inflammatory disease that is often
      accompanied by interstitial lung disease (ILD) or internal malignancy. New
      autoantibodies, anti-clinically amyopathic dermatomyositis 140 (anti-CADM-140)
      antibody (Ab) and anti-155/140 Ab, as well as anti-aminoacyl-tRNA synthetase
      (anti-ARS) Ab and anti-Mi-2 Ab, have been discovered and their utility indicated.
      However, the association between these autoantibodies and the clinical
      characteristics of DM is not fully understood, and it is unclear whether anti
      155/140 Ab is "specific" to DM patients with internal malignancy. Therefore, we
      analyzed 55 DM patients and 18 non-DM patients with malignancy to evaluate the
      clinical characteristics, especially skin manifestations, in association with DM
      specific autoantibodies detected by immunoprecipitation. Six patients (11%) had
      anti-CADM-140 Ab, nine (16%) had anti-155/140 Ab, eight (15%) had anti-ARS Ab and
      six (11%) had anti-Mi-2 Ab. The frequency of DM patients positive for any type of
      autoantibody was 53%. Among the 20 DM patients with ILD, three (15%) had both
      anti-CADM-140 Ab and rapidly progressive ILD, and required intensive therapy (P <
      0.05). ILD found in anti-ARS Ab-positive patients did not progress rapidly. The
      prevalence of muscle involvement in patients with anti-CADM-140 Ab was 83%. Among
      the 18 DM patients with internal malignancy, four (22%) had anti-155/140 Ab, and
      internal malignancy was found in four cases (44%) of nine anti-155/140 Ab
      positive patients. None of the non-DM patients with malignancy were positive for
      anti-155/140 Ab. In conclusion, the results of the present study indicate that
      anti-155/140 Ab is specific to DM patients with internal malignancy and that we
      may be able to predict prognosis of ILD and the presence of malignancy to some
      extent, suggesting that examination of autoantibodies in DM patients is
      clinically very useful. However, further investigation is needed because several
      findings differ from those of previous reports.

PMID- 21883413
TI  - Inhibition of motility in isolated horse small intestine is mediated by kappa but
      not u opioid receptors.
AB  - The effects of preferential u (morphine), selective u (fentanyl), selective kappa
      (compound U69593) opioid receptor agonists, and nonselective (naloxone) and
      selective u (naloxonazine) antagonists on equine small intestinal motility were
      evaluated in vitro. Samples of circular muscle from equine jejunum were placed in
      isolated organ baths and drug-induced modifications of both spontaneous and
      electrically evoked contractile activity were measured. None of the opioid
      agonists induced a significant change in spontaneous contractions. Fentanyl and
      U69593 reduced electrically induced contractions, whereas morphine reduced them
      only slightly. Naloxone competitively antagonised U69593, but both naloxone and
      naloxonazine were unable to counteract the inhibition of contractions induced by
      fentanyl. The inhibition of contractions shown by fentanyl is therefore probably
      not mediated by opioid receptors, but due to an anticholinergic activity of this
      drug. In summary, these data showed an inhibitory effect exerted by kappa
      receptors on equine small intestinal motility, whereas the role of u receptors
      seemed marginal and would need further characterisation.

PMID- 21883414
TI  - Catastrophic scapular fractures in Californian racehorses: pathology, morphometry
      and bone density.
AB  - REASONS FOR PERFORMING STUDY: To enhance understanding of the nature and
      pathogenesis of scapular fractures in racehorses. HYPOTHESIS: Scapular fractures
      in racehorses have a consistent configuration related to sites of pre-existing
      stress modelling and remodelling. METHODS: Fractured and intact scapulae
      collected post mortem were examined visually and with computed tomography (CT).
      Scapular fracture configuration, bone modelling changes and standardised CT
      morphometry and density measurements were recorded. Statistical comparisons were
      made between fractured, nonfractured contralateral and control scapulae. RESULTS:
      Thirty-nine scapulae from 10 Thoroughbred (TB) and 10 Quarter Horse (QH)
      racehorses were obtained. All 14 fractured scapulae (from 12 horses) had a
      consistent comminuted fracture configuration. A complete fracture coursed
      transversely through the neck of the scapula at the level of the distal aspect of
      the spine (8.9 +/- 0.9 cm proximal to the lateral articular margin of the glenoid
      cavity). The distal fragment of 13 fractured scapulae was split into 2 major
      fragments by a fracture in the frontal plane that entered the glenoid cavity (2.8
      +/- 0.4 cm caudal to the cranial articular margin). Focal areas of periosteal
      proliferation and/or radiolucency were present in the distal aspect of the
      scapular spine of all fractured and intact contralateral scapulae, but less
      commonly (P<0.01) in intact scapula from horses without a scapular fracture.
      Fractured scapulae had 7-10% lower mean density and 46-104% greater density
      heterogeneity in the spine adjacent to the transverse fracture compared to
      control scapulae (P<0.03). CONCLUSIONS AND CLINICAL RELEVANCE: Thoroughbred and
      QH racehorses have a characteristic scapular fracture configuration that is
      associated with pre-existing pathology of the distal aspect of the spine. This
      location is consistent with scapular stress fractures diagnosed in lame TB
      racehorses. Catastrophic fracture is the acute manifestation of a more chronic
      process. Consequently, there are opportunities for early detection and prevention
      of fatalities.

PMID- 21883415
TI  - The in vitro effects of antibiotics on cell viability and gene expression of
      equine bone marrow-derived mesenchymal stromal cells.
AB  - OBJECTIVES: To investigate the effects of commonly used antibiotics on cell
      viability and gene expression of equine bone marrow-derived mesenchymal stromal
      cells (MSC) in vitro. MATERIALS AND METHODS: Bone marrow-derived MSC were
      cultured in media containing gentamicin, amikacin, penicillin, enrofloxacin or
      ceftiofur at concentrations of 50, 100, 200 and 500 ug/ml. The alamarBlue
      fluorescence assay was used to assess cell viability over 48 h. After 5 days the
      cells were released and lysed prior to RNA extraction and reverse transcription.
      RNA levels were assessed using spectrophotometry and quantitative PCR was used to
      analyse gene expression of COL1A2, COL5A1, TNC, TNFalpha, CASP3, BCl2 and
      TGFbetaR2 relative to the reference gene GAPDH. RESULTS: Enrofloxacin produced a
      significant concentration-dependent reduction in cell viability at 200 ug/ml and
      higher concentrations (P = 0.009). Amikacin significantly reduced cell viability
      at 500 ug/ml (P = 0.002). Penicillin had no effect on cell viability at the
      concentrations tested (P = 0.18). Gentamicin and ceftiofur showed some
      interaction with the assay but had no overall effect on cell viability. At 500
      ug/ml gentamicin (P<0.001), amikacin (P = 0.03), enrofloxacin (P<0.001) and
      ceftiofur (P<0.001) caused significant reductions in RNA levels. At 50 ug/ml
      gentamicin (P<0.001) and amikacin (P = 0.019) reduced BCl2 expression.
      Enrofloxacin produced a significant increase in COL1A2 expression (P<0.001).
      CONCLUSIONS: Enrofloxacin reduced MSC viability in vitro and may require cautious
      use in clinical situations. Penicillin has minimal detrimental effects on MSC in
      vitro and its use in conjunction with MSC at implantation appears safe. Further
      work is needed to fully investigate the effects of gentamicin, amikacin and
      ceftiofur. POTENTIAL RELEVANCE: Clinicians using local antibiotic administration
      should consider the potential for local toxicity as well as the need for
      effective concentrations of the antibiotic.

PMID- 21883416
TI  - Management of hindlimb proximal suspensory desmopathy by neurectomy of the deep
      branch of the lateral plantar nerve and plantar fasciotomy: 155 horses (2003
      2008).
AB  - REASONS FOR PERFORMING STUDY: Neurectomy of the deep branch of the lateral
      plantar nerve and plantar fasciotomy have become accepted as methods of treatment
      of proximal suspensory desmopathy (PSD), but there are limited long-term studies
      documenting the outcome. OBJECTIVES: To describe long-term follow-up in horses
      with PSD alone or with other injuries contributing to lameness and poor
      performance, including complications, following neurectomy and fasciotomy.
      METHODS: Follow-up information was acquired for 155 horses that had undergone
      neurectomy and fasciotomy for treatment of PSD between 2003 and 2008. Success was
      classified as a horse having been in full work for >1 year post operatively.
      Horses were divided into 3 groups on the basis of the results of clinical
      assessment and diagnostic analgesia. Horses in Group 1 had primary PSD and no
      other musculoskeletal problem. Horses in Group 2 had primary PSD in association
      with straight hock conformation and/or hyperextension of the metatarsophalangeal
      joint. Horses in Group 3 had PSD and other problems contributing to lameness or
      poor performance. RESULTS: In Group 1, 70 of 90 horses (77.8%) had a successful
      outcome, whereas in Group 3, 23 of 52 horses (44.2%) returned to full function
      for >1 year. Complications included iatrogenic damage to the plantar aspect of
      the suspensory ligament, seroma formation, residual curb-like swellings and the
      development of white hairs. All horses in Group 2 remained lame. CONCLUSIONS AND
      CLINICAL RELEVANCE: There is a role for neurectomy of the deep branch of the
      lateral plantar nerve and plantar fasciotomy for long-term management of hindlimb
      PSD, but a prerequisite for successful management requires recognition of risk
      factors for poor outcome including conformation features of straight hock or
      fetlock hyperextension.

PMID- 21883417
TI  - An evaluation of the Abaxis VSPro for the measurement of equine plasma fibrinogen
      concentrations.
AB  - REASONS FOR PERFORMING STUDY: Accurate measurement of plasma fibrinogen
      concentrations is an important tool for assessment of horses with inflammatory
      diseases. OBJECTIVES: To determine the precision and accuracy of a benchtop
      instrument using both fresh and frozen equine plasma by comparing the plasma
      fibrinogen concentration measured by a benchtop instrument to 2 separate
      laboratory standard methods (ACL 100 and STA Compact) for fibrinogen measurement.
      METHODS: Accuracy and precision of the VSPro was evaluated using both human
      fibrinogen standards and samples from horses. Fifty frozen samples from horses
      with gastrointestinal disease had the fibrinogen concentration measured using the
      ACL 1000 and the VSPro. Fifty fresh samples were collected from hospitalised
      horses and fibrinogen concentration was measured using the STA Compact
      coagulation machine and the VSPro. Correlations for measurements were performed,
      as well as Bland-Altman analysis. RESULTS: Coefficients of variability for the
      VSPro ranged from 7% to 15%. The VSPro fibrinogen values were well correlated to
      both the ACL 1000 (r = 0.94, P<0.001) and the STA Compact measurements (r =
      0.926, P<0.001). Bland-Altman analysis showed a mean bias of -0.83 g/l (95%
      confidence interval -2.03-0.324 g/l) for the ACL 1000 and a mean bias of -0.024
      g/l (95% confidence interval -1.434-1.386 g/l) for the STA Compact. CONCLUSIONS:
      The VSPro appears to have adequate accuracy and precision for clinical
      measurement of plasma fibrinogen concentrations. POTENTIAL RELEVANCE: The VSPro
      provides a measurement of equine plasma fibrinogen concentration using a benchtop
      instrument with a rapid test time that has comparable accuracy to the fibrinogen
      concentration obtained from reference laboratories.

PMID- 21883418
TI  - A randomised, double-blinded, placebo-controlled study on the efficacy of a
      unique extract of green-lipped mussel (Perna canaliculus) in horses with chronic
      fetlock lameness attributed to osteoarthritis.
AB  - REASONS FOR PERFORMING STUDY: Lyophilised products from green-lipped mussel
      (Perna canaliculus[LPPC]) are used to orally treat horses with osteoarthritis
      (OA). However, no randomised, controlled or double-blinded studies on the
      efficacy of this treatment in horses have been reported to date. OBJECTIVE: To
      investigate the effects of a unique LPPC (Biolane)(1) in improving clinical signs
      of OA in the fetlock. METHODS: Data were analysed from 26 horses with primary
      fetlock lameness in a controlled, randomised and double-blinded, multi-centre
      clinical trial. The study design was a partial crossover with a washout period
      and consisted of 19 horses treated with LPPC and 20 with a placebo. Horses were
      dosed orally with 25 mg/kg bwt/day LPPC or placebo for 56 days. Efficacy was
      evaluated by clinical assessment of lameness, passive flexion, pain, swelling and
      heat in the affected joint. Relationships between variables were analysed using
      an ordinal logistic model with random effects for horse and horse x treatment
      according to a modified intention-to-treat analysis. RESULTS: Clinical evaluation
      of horses with a fetlock lameness treated with LPPC showed a significant
      reduction in severity of lameness (P<0.001), improved response to the joint
      flexion test (P<0.001) and reduced joint pain (P = 0.014) when compared with
      horses treated with placebo. CONCLUSIONS: The LPPC significantly alleviated the
      severity of lameness and joint pain and improved response to joint flexion in
      horses with lameness attributable to OA in the fetlock.

PMID- 21883419
TI  - A clinico-demographic analysis of maxillofacial trauma in the elderly.
AB  - INTRODUCTION: The elderly represent an increasing proportion of society.
      Management of maxillofacial trauma in this population may be complicated by
      coexisting medical conditions, requiring multi-disciplinary care. METHODS: This
      retrospective audit assesses the incidence and pattern of maxillofacial trauma in
      elderly patients (>=60 years) presented to the Merseyside Regional Maxillofacial
      Unit. Over the time period of 2003, 2004 and 2005, 7905 trauma patients presented
      to the accident and emergency department, of whom 757 were elderly (10%).
      RESULTS: Results indicated that the male to female ratio was 1:1.4. The commonest
      cause of injury was a fall (83%) followed by an assault (6%); the majority of
      falls occurring in the home. CONCLUSION: Management of maxillofacial injuries in
      this population should focus on targeted prevention programmes, which address
      known risk factors for falling. We believe that this is a public health issue.
      Members of the maxillofacial team should be aware of common risk factors of falls
      in elderly. Better collaboration with the Medicine for Elderly team should be
      considered at an early stage on managing these patients.

PMID- 21883420
TI  - Knowledge and attitudes of dentists regarding ageing and the elderly.
AB  - OBJECTIVE: This study was aimed to identify the knowledge and attitudes of
      dentists regarding ageing and the elderly. BACKGROUND: As the population ages,
      there is a greater demand for differentiated care from health professionals.
      However, the treatment needs of the elderly population are not sufficiently
      addressed, particularly in developing countries. MATERIALS AND METHODS: An
      official list of all dentists registered in the city of Belo Horizonte, Brazil,
      was obtained from the Regional Dentistry Council. A questionnaire was delivered
      to 276 randomly selected dentists; the survey contained questions designed to
      characterise the sample and identify dentists' conduct towards elderly patients.
      A Likert scale was used to identify knowledge regarding care for the elderly and
      attitudes towards ageing. RESULTS: Women demonstrated more positive attitudes
      towards the elderly. Graduates who worked in the public sector demonstrated a
      greater knowledge of geriatric dentistry (p < 0.05). Attending specific
      continuing education courses had no influence over the dentists' willingness to
      treat the elderly population. Significant associations were not found between
      attitudes and knowledge regarding the elderly. CONCLUSION: Dentists who worked in
      the public sector demonstrated a greater knowledge regarding the elderly. This
      knowledge did not influence attitudes towards ageing. Women demonstrated a more
      positive attitude regarding ageing and dental care.

PMID- 21883421
TI  - Management of a post-radiotherapy xerostomic patient--a case report.
AB  - OBJECTIVE: The objective of the study was to fabricate complete denture with
      palatal reservoir filled with artificial saliva for a post radiotherapy
      edentulous patient. BACKGROUND: Xerostomia is a subjective complaint rather than
      a disease. It is caused by irradiation, medication, Sjogren's syndrome &
      neurological factors such as stress. Radiotherapeutic treatment of head and neck
      cancer patients often causes long term dysfunction involving their salivary
      function, swallowing capabilities & taste. All three of these domains are
      affected by radiation- induced damage to the salivary glands. This in turn
      results in poor retention of complete denture, frequent trauma to alveolar ridge
      & other oral infections. All these events drastically affects quality of life of
      ageing patients. MATERIAL AND METHOD: A complete denture in heat cure acrylic
      resin was fabricated in which a palatal reservoir was made on the palatal side.
      RESULTS: Problems arising due to xerostomia were reduced to a great extent.
      CONCLUSION: Prosthodontic management of Xerostomic patient include several
      techniques. This paper presents a case report of post radiotherapy edentulous
      patient in which complete denture with palatal reservoir filled with artificial
      saliva was fabricated.

PMID- 21883422
TI  - Impact of tooth loss on the quality of life.
AB  - INTRODUCTION: There is scientific evidence that shows health contributes to the
      quality of life. These measurements have not been well guided towards the free
      response of oral health in people's lives. OBJECTIVE: This study aimed to
      investigate the impact of tooth loss on the quality of life of elderly people.
      MATERIAL AND METHODS: Qualitative investigation with descriptive features - which
      used a random sample out of the total edentulous elderly people, who lived in an
      institution in Fortaleza, Brazil - was carried out. From 250 residents screened,
      72 completely edentulous elderly, with ages from 60 to 79 years were selected. A
      semi-structured questionnaire was used with closed and opened questions in which
      the last one was used for the free flow of the interviewee's responses. The
      content was analysed and codified according to Bardin. RESULTS: In total, 84.7%
      had attended the dentist to have exodontia. Of them, 81.9% reported difficulties
      after losing their teeth. Physical dimensions, characterised by the difficulties
      in eating and social dimensions, because of interference in communication with
      other people were obtained. CONCLUSION: Tooth loss causes disorder in the
      individual's quality of life, mainly when it affects their well-being and
      appearance.

PMID- 21883423
TI  - Association between oral health, cognitive impairment and oral health-related
      quality of life.
AB  - OBJECTIVE: Investigating oral health-related quality of life's (OH-QoL)
      relationship with cognitive state. BACKGROUND: Oral health affects OH-QoL and is
      poor in institutionalised and cognitively impaired people. MATERIAL AND METHODS:
      This was a cross-sectional study involving 215 institutionalised elderly (82.9
      mean age), who were interviewed, examined and cognitively screened using the
      Pfeiffer test. RESULTS: Mean GOHAI score was 53.1; only 43.7% of the participants
      reported having a good OH-QoL. Needing help with dressing or washing (OR 2.14; p
      = 0.004), having one to nine teeth (OR 4.65; p >= 0.001), eight or less occluding
      pairs (OR 2.74; p = 0.002), one to three caries (OR 1.85; p = 0.005) and being
      cognitive impaired (OR 0.54; p = 0.034) were significantly associated with
      altered OH-QoL in bi-variate analysis. Being edentulous (OR 3.18; p = 0.0046),
      having 1-9 teeth (OR 2.62; p = 0.056) and presenting mild cognitive impairment
      (MCI) (OR 0.32; p = 0.016) appeared as predictive variables in logistic
      regression for having an altered OH-QoL. CONCLUSIONS: Participants having MCI had
      significantly better GOHAI score than cognitively normal residents. Performing
      cognitive screening parallel to applying any OH-QoL instrument would make the
      results more reliable and would benefit cognitively impaired people.

PMID- 21883424
TI  - The efficacy of a topical gel with triester glycerol oxide in denture-related
      mucosal injuries.
AB  - OBJECTIVE: The efficacy of a topical gel with triester glycerol oxide for
      treating ulcerations related to new complete dentures was studied and compared
      with a placebo gel. MATERIALS AND METHODS: Fifty edentulous patients were
      enrolled in this double-blind clinical study. All subjects received new maxillary
      and mandibular complete dentures and were recalled 1, 3 and 7 days after denture
      placement. Twenty-five subjects received topical gel with triester glycerol oxide
      (TGO), and 25 subjects received topical gel without TGO. At each visit, pain and
      discomfort with the new dentures was assessed, and at the last visit, healing of
      ulcerations was also graded by a clinician. Subjects also graded the gel's taste,
      smell and ease of use. RESULTS: Specifically, there was no statistically
      significant difference in ulcer healing (p > 0.05), ratings of smell, taste and
      ease of use (p > 0.05) or pain and discomfort scores (p > 0.05). However, within
      group differences were observed in pain and discomfort scores between follow-up
      sessions (p = 0.01 for all comparisons). CONCLUSION: Clinically, TGO gel is not
      effective in the treatment of mucosal injuries occurring following placement of
      complete dentures.

PMID- 21883425
TI  - Complete denture wearing and fractures among edentulous patients treated in
      university clinics.
AB  - OBJECTIVE: The prevalence of wearing and fracture of complete dentures was
      evaluated among edentulous patients treated in two dental schools in Brazil.
      BACKGROUND: Acceptance and wearing of complete dentures are related to adaptive
      behaviour of edentulous patients. However, one reason that could interfere with
      the wearing dentures is their potential to fracture, which is still a common
      complication in denture rehabilitation practice. MATERIAL AND METHODS: Two
      hundred and twenty-four edentulous patients rehabilitated with complete dentures
      from 2000 to 2005 in Aracatuba and Araraquara Dental School, University of State
      of Sao Paulo, were assessed in 2006 and 2007 to answer a questionnaire about
      wearing and fracture of their dentures. Statistical analysis were performed using
      Epi Info software and chi-squared test to compare maxillary and mandibular data
      (alpha = 0.05). RESULTS: Almost 26% of the patients did not wear their dentures,
      and among the remainder, the majority wore the maxillary denture. About 30% of
      the dentures were fractured, with higher prevalence in the maxillary arch (p =
      0.003). CONCLUSIONS: Discontinuation of wearing dentures was quite high,
      especially considering the treatment which was carried out in university clinics.
      Prevalence of fractures was also high, greater for the maxillary denture, and was
      one of the main reasons for non-wearing of complete dentures.

PMID- 21883426
TI  - Analysis of current therapy and clinical outcome in childhood pemphigus vulgaris.
AB  - Pemphigus vulgaris (PV) is a rare, potentially fatal chronic autoimmune disease
      of the skin and mucous membrane. The objective of this study was to analyze the
      clinical outcomes and side effects associated with treatment of childhood PV
      (CPV). A retrospective review of the English language literature was conducted
      through PUBMED using the words childhood pemphigus vulgaris, and treatment or
      clinical outcome. Only patients under 12 years of age were included. Thirty-three
      cases were found in 29 reports. Mean age at onset was 8.3 years (range 1.5-12
      yrs). Mucosal involvement (97.0%) was more common than cutaneous involvement
      (84.8%). Oral mucosa was the most common site of mucosal involvement (93.9%),
      followed by genital (20.6%), ocular (11.8%), and nasal mucosa (2.9%). Mean
      duration of therapy was 4.5 years (range 0.6-14.5 yrs), and mean duration of
      follow-up was 5.2 years (range 0.6-16 yrs). Complete recovery with no further
      therapy was achieved in 18.2% and partial recovery with minor relapses while on
      maintenance therapy in 78.8%. One patient died due to infection (3.0%). Serious
      side effects were present in 60.6%. The most common were cushingoid features
      (65.0%), growth retardation (50.0%), and infection (50.0%). Two patients who were
      refractory to systemic corticosteroids and immunosuppressive agents (ISA) had a
      favorable clinical response to Rituximab. Current therapy for CPV involving the
      use of long-term systemic corticosteroids in conjunction with ISA results in
      prolonged immunosuppression, causing systemic infections and growth retardation.
      Safer and more effective therapies need to be explored.

PMID- 21883428
TI  - Miscoding, misclassification and misdiagnosis of diabetes in primary care.
AB  - AIMS: To determine the effectiveness of self-audit tools designed to detect
      miscoding, misclassification and misdiagnosis of diabetes in primary care.
      METHODS: We developed six searches to identify people with diabetes with
      potential classification errors. The search results were automatically ranked
      from most to least likely to have an underlying problem. Eight practices with a
      combined population of 72,000 and diabetes prevalence 2.9% (n = 2340) completed
      audit forms to verify whether additional information within the patients' medical
      record confirmed or refuted the problems identified. RESULTS: The searches
      identified 347 records, mean 42 per practice. Pre-audit 20% (n = 69) had Type 1
      diabetes, 70% (n = 241) had Type 2 diabetes, 9% (n = 30) had vague codes that
      were hard to classify, 2% (n = 6) were not coded and one person was labelled as
      having gestational diabetes. Of records, 39.2% (n = 136) had important errors:
      10% (n = 35) had coding errors; 12.1% (42) were misclassified; and 17.0% (59)
      misdiagnosed as having diabetes. Thirty-two per cent (n = 22) of people with Type
      2 diabetes (n = 69) were misclassified as having Type 1 diabetes; 20% (n = 48) of
      people with Type 2 diabetes (n = 241) did not have diabetes; of the 30 patients
      with vague diagnostic terms, 50% had Type 2 diabetes, 20% had Type 1 diabetes and
      20% did not have diabetes. Examples of misdiagnosis were found in all practices,
      misclassification in seven and miscoding in six. CONCLUSIONS: Volunteer practices
      successfully used these self-audit tools. Approximately 40% of patients
      identified by computer searches (5.8% of people with diabetes) had errors;
      misdiagnosis is commonest, misclassification may affect treatment options and
      miscoding in omission from disease registers and the potential for reduced
      quality of care.

PMID- 21883427
TI  - A case of unicommissural unicuspid aortic valve stenosis diagnosed by real time
      three-dimensional transesophageal echocardiography.

PMID- 21883429
TI  - Impaired fasting glucose, ancestry and waist-to-height ratio: main predictors of
      incident diagnosed diabetes in the Canary Islands.
AB  - AIMS: To estimate the incidence rate and risk factors for diabetes in the Canary
      Islands. METHODS: A total of 5521 adults without diabetes were followed for a
      median of 3.5 years. Incident cases of diabetes were self-declared and validated
      in medical records. The following factors were assessed by Cox regression to
      estimate the hazard ratios for diabetes: impaired fasting glucose (5.6 mmol/l <=
      fasting glucose <= 6.9 mmol/l), BMI, waist-to-height ratio (>= 0.55), insulin
      resistance (defined as triglycerides/HDL cholesterol >= 3), familial antecedents
      of diabetes, Canarian ancestry, smoking, alcohol intake, sedentary lifestyle,
      Mediterranean diet, social class and the metabolic syndrome. RESULTS: The
      incidence rate was 7.5/10(3) person-years (95% CI 6.4-8.8). The greatest risks
      were obtained for impaired fasting glucose (hazard ratio 2.6; 95% CI 1.8-3.8),
      Canarian ancestry (hazard ratio 1.9; 95% CI 1.0-3.4), waist-to-height ratio
      (hazard ratio 1.7; 95% CI 1.1-2.5), insulin resistance (hazard ratio 1.5; 95% CI
      1.0-2.2) and paternal history of diabetes (hazard ratio 1.5; 95% CI 1.0-2.3). The
      metabolic syndrome (hazard ratio 1.9; 95% CI 1.3-2.8) and BMI >= 30 kg/m(2)
      (hazard ratio 1.7; 95% CI 1.0-2.7) were significant only when their effects were
      not adjusted for impaired fasting glucose and waist-to-height ratio,
      respectively. CONCLUSIONS: The incidence of diabetes in the Canary Islands is 1.5
      fold higher than that in continental Spain and 1.7-fold higher than in the UK.
      The main predictors of diabetes were impaired fasting glucose, Canarian ancestry,
      waist-to-height ratio and insulin resistance. The metabolic syndrome predicted
      diabetes only when its effect was not adjusted for impaired fasting glucose. In
      individuals with Canarian ancestry, genetic susceptibility studies may be
      advisable. In order to propose preventive strategies, impaired fasting glucose,
      waist-to-height ratio and triglyceride/HDL cholesterol should be used to identify
      subjects with an increased risk of developing diabetes.

PMID- 21883430
TI  - Diabetes medication patient safety incident reports to the National Reporting and
      Learning Service: the care home setting.
AB  - AIMS: To analyse adverse drug events in older people with diabetes in the care
      home setting via incident reports obtained from the National Reporting and
      Learning Service. METHODS: A Freedom of Information request was made to the
      National Reporting and Learning Service via the National Patient Safety Agency.
      Within the National Reporting and Learning Service, reports on diabetes within
      the category of 'medication' using the location limiter of 'hospice or nursing
      home or residential home' were searched. We requested information about the
      number and nature of adverse drug event reports that had been received in
      relation to diabetes. The data were subdivided into reports (1) relating to
      insulin therapy and (2) oral glucose-lowering agents. RESULTS: Data were
      collected between 1 January 2005 and 31 December 2009. There were 684 reports
      related to insulin and 84 incidents related to oral glucose-lowering agents. The
      most common error category with both types of drug therapy was wrong or unclear
      dose: 173 reports for insulin, including one death, and 20 reports for oral
      therapy. CONCLUSIONS: Residents with diabetes in care homes are potentially at
      risk of harm from adverse drug events pertaining to insulin and oral glucose
      lowering agents. Because of under-reporting, our data most likely represent only
      a fraction of events.

PMID- 21883431
TI  - Prevalence, awareness and treatment of type 2 diabetes mellitus in Switzerland:
      the CoLaus study.
AB  - AIMS: To assess the prevalence, awareness and treatment levels of Type 2 diabetes
      in a Swiss city. METHODS: Population-based cross-sectional study of 6181 subjects
      (3246 women) aged 35-75 years living in Lausanne, Switzerland. Type 2 diabetes
      was defined as fasting plasma glucose >= 7 mmol/l and/or oral hypoglycaemic
      treatment and/or insulin. RESULTS: Total prevalence of Type 2 diabetes was 6.3%
      (95% confidence interval: 5.7-7.0%), higher in men (9.1%) than in women (3.8%, P
      < 0.001) and increased with age. Two-thirds (65.3%; 60.4-70.0%) of participants
      with Type 2 diabetes were aware of their status and among those aware 86.0% (81.5
      90.3%) were treated. Treatment was more frequent in men (91.3%) than in women
      (75.9%, P < 0.001). Two-thirds of those treated for Type 2 diabetes were on
      monotherapy. Biguanides were prescribed in 65.0% of Type 2 diabetes patients and
      represented 48% of all antidiabetic drugs. Multivariable analysis showed male
      gender, increasing age, waist or BMI to be positively associated with prevalence
      of Type 2 diabetes, while leisure-time physical activity and alcohol consumption
      were negatively associated. Among participants presenting with Type 2 diabetes,
      increasing age was positively associated with awareness of Type 2 diabetes. Among
      subjects diagnosed with Type 2 diabetes, male gender and increasing age were
      positively associated with treatment. CONCLUSION: Prevalence of Type 2 diabetes
      in Switzerland is estimated to be between 5.7% and 7.0%. Two-thirds of patients
      with Type 2 diabetes are aware of their status, and over three quarters of those
      aware are treated.

PMID- 21883433
TI  - Clark et al. Nurse-led interventions used to improve control of high blood
      pressure in people with diabetes: a systematic review and meta analysis.

PMID- 21883434
TI  - Time trends in absolute and modifiable coronary heart disease risk in patients
      with Type 2 diabetes in the Swedish National Diabetes Register (NDR) 2003-2008.
AB  - AIMS: The aim was to evaluate treatment goal achievements early in the course of
      Type 2 diabetes, and their effect on 10-year risk of coronary heart disease in
      patients receiving usual care. METHODS: Assessment of risk factor control 3 years
      after diagnosis in patients with Type 2 diabetes with no previous coronary heart
      disease included from the Swedish National Diabetes Register; a total of 19,382
      patients (mean age 58 years) in cross-sectional surveys from 2003 to 2008, and a
      subgroup of 4293 patients followed individually from year of diagnosis to follow
      up after a mean 2.6 years. Estimation of absolute 10-year risk of coronary heart
      disease using the U.K. Prospective Diabetes Study risk engine, and modifiable 10
      year risk defined as percentage excess risk above patients with 'normal' risk
      factor values. RESULTS: Treatment goals for HbA1c , blood pressure, total and LDL
      cholesterol were achieved in 78.4, 65.5, 55.6% and 61.0%, respectively, in the
      cross-sectional survey in 2008, following a trend of generally improved control.
      In the individually followed patients in the subgroup, mean absolute 10-year
      coronary heart disease risk increased from 13.7% (men/women 16.9/9.5%) to 14.2
      (men/women 17.6/9.6%) (P < 0.001) from year of diagnosis to follow-up after 2.6
      years, while mean modifiable risk decreased from 37.7% (men/women 28.6/49.9%) to
      19.1% (13.2/26.9%) (P < 0.001 in all). CONCLUSIONS: A high achievement of
      treatment goals and a low mean modifiable 10-year coronary heart disease risk was
      found at the 3-year follow-up, both in the cross-sectional survey in 2008 and in
      patients individually followed since diagnosis. This indicates the feasibility
      and significance of early multifactorial risk factor treatment.

PMID- 21883435
TI  - Patient satisfaction and barriers to initiating real-time continuous glucose
      monitoring in early pregnancy in women with diabetes.
AB  - AIM: To evaluate self-reported satisfaction and barriers to initiating real-time
      continuous glucose monitoring in early pregnancy among women with pregestational
      diabetes. METHODS: Fifty-four women with Type 1 diabetes and 14 women with Type 2
      diabetes were offered continuous glucose monitoring for 6 days at median 9 (range
      6-14) gestational weeks and were asked to answer a semi-structured questionnaire
      on patient satisfaction. RESULTS: Median HbA1c was 49 (range 34-86) mmol/mol)
      [6.6 (5.3-10.0) %] and duration of diabetes was 12 (0.5-37) years. Continuous
      glucose monitoring was used for 6 (0.5-7) days, with 43 (65%) women using
      continuous glucose monitoring for at least 5 days. The women experienced 2.7 (0
      12) alarms per 24 h, of which approximately one third was technical alarms and
      one third disturbed their sleep. Sixteen women (24%) reported discomfort with
      continuous glucose monitoring during daytime and twelve (18%) during sleep. Many
      women reported improved diabetes understanding (52%) and would recommend
      continuous glucose monitoring to others (83%). Twenty-four patients (36%) had
      continuous glucose monitoring removed earlier than planned ( before the intended
      6 days of initial monitoring). Ten women (15%) did not wish to use continuous
      glucose monitoring again in pregnancy. Main causes behind early removal of
      continuous glucose monitoring were self-reported skin irritation, technical
      problems and continuous glucose monitoring inaccuracy. No differences were found
      in continuous glucose monitoring use, inconvenience or compliance with respect to
      diabetes type. CONCLUSIONS: The majority of pregnant women with diabetes found
      real-time continuous glucose monitoring useful and the intervention was equally
      tolerated regardless of diabetes type. Nevertheless, continuous glucose
      monitoring was frequently removed earlier than planned, primarily because of skin
      irritation, technical problems and inaccuracy.

PMID- 21883436
TI  - Increased prevalence of chronic kidney disease in patients with Type 1 diabetes
      and non-alcoholic fatty liver.
AB  - AIMS: We determined whether non-alcoholic fatty liver is associated with an
      increased prevalence of chronic kidney disease in Type 1 diabetes. METHODS: We
      studied 343 patients with Type 1 diabetes, who had no history of excessive
      alcohol consumption or other secondary causes of chronic liver disease. Non
      alcoholic fatty liver was diagnosed by ultrasonography. Chronic kidney disease
      was defined as presence of either abnormal albuminuria (i.e., urinary
      albumin/creatinine ratio >= 30 mg/g) or estimated glomerular filtration rate of
      less than 60 ml min(-1)  1.73 m(-2) . RESULTS: Compared with those without
      steatosis, patients with non-alcoholic fatty liver (n = 182) had significantly
      lower estimated GFR (83.0 +/- 27 vs. 93.3 +/- 29 ml min(-1)  1.73 m(-2) , P <
      0.001) and a greater prevalence of abnormal albuminuria (50.0 vs. 20.5%, P <
      0.0001) and chronic kidney disease (54.4 vs. 24.2%, P < 0.0001). Multivariable
      logistic regression analysis revealed that non-alcoholic fatty liver was
      associated with an increased risk of either abnormal albuminuria (adjusted odds
      ratio 2.21, 95% CI 1.2-4.1, P = 0.01) or chronic kidney disease (adjusted odds
      ratio 1.93, 95% CI 1.1-3.6, P = 0.02), independently of age, gender, smoking
      status, physical activity, diabetes duration, HbA(1c) , BMI, systolic blood
      pressure, plasma lipids and use of anti-hypertensive and lipid-lowering
      medications. CONCLUSIONS: Our findings demonstrate that ultrasound-diagnosed non
      alcoholic fatty liver is associated with a higher prevalence of chronic kidney
      disease in patients with Type 1 diabetes, independently of several risk factors,
      including the components of the metabolic syndrome.

PMID- 21883437
TI  - Validation of a single-sample urinary C-peptide creatinine ratio as a
      reproducible alternative to serum C-peptide in patients with Type 2 diabetes.
AB  - AIMS: Serum C-peptide can be used in Type 2 diabetes as a measure of endogenous
      insulin secretion, but practicalities of collection limit its routine clinical
      use. Urine C-peptide creatinine ratio is a non-invasive alternative that is
      stable for at least 3 days at room temperature in boric acid preservative. We
      aimed to assess the utility of urine C-peptide creatinine ratio in individuals
      with Type 2 diabetes as an alternative to serum C-peptide. METHODS: We assessed,
      in 77 individuals with Type 2 diabetes, the reproducibility of, and correlations
      between, fasting and postprandial urine C-peptide creatinine ratio and serum C
      peptide, and the impact of renal impairment (estimated glomerular filtration rate
      < 60 ml min(-1) 1.73 m(-2)) on these correlations. RESULTS: Urine C-peptide
      creatinine ratio was at least as reproducible as serum C-peptide [fasting
      coefficient of variation mean (95% CI): 28 (21-35)% vs. 38 (26-59)% and 2-h post
      meal 26 (18-33)% vs. 27 (20-34)%. Urine C-peptide creatinine ratio 2 h post-meal
      was correlated with stimulated serum C-peptide, both the 2-h value (r = 0.64, P <
      0.001) and the 2-h area under the C-peptide curve (r = 0.63, P < 0.001). The
      association seen was similar in patients with and without moderate renal
      impairment (P = 0.6). CONCLUSIONS: In patients with Type 2 diabetes, a single
      urine C-peptide creatinine ratio is a stable, reproducible measure that is well
      correlated with serum C-peptide following meal stimulation, even if there is
      moderate renal impairment. Urine C-peptide creatinine ratio therefore has
      potential for use in clinical practice in the assessment of Type 2 diabetes.

PMID- 21883438
TI  - Cost-utility analysis of liraglutide compared with sulphonylurea or sitagliptin,
      all as add-on to metformin monotherapy in Type 2 diabetes mellitus.
AB  - AIM: To investigate the cost-effectiveness of liraglutide as add-on to metformin
      vs. glimepiride or sitagliptin in patients with Type 2 diabetes uncontrolled with
      first-line metformin. METHODS: Data were sourced from a clinical trial comparing
      liraglutide vs. glimepiride, both in combination with metformin, and a clinical
      trial comparing liraglutide vs. sitagliptin, both as add-on to metformin. Only
      the subgroup of patients in whom liraglutide was added to metformin monotherapy
      was included in the cost-utility analysis. The CORE Diabetes Model was used to
      simulate outcomes and costs with liraglutide 1.2 and 1.8 mg vs. glimepiride and
      vs. sitagliptin over patients' lifetimes. Treatment effects were taken directly
      from the trials. Costs and outcomes were discounted at 3.5% per annum and costs
      were accounted from a third-party payer (UK National Health System) perspective.
      RESULTS: Treatment with liraglutide 1.2 and 1.8 mg resulted, respectively, in
      mean increases in quality-adjusted life expectancy of 0.32 +/- 0.15 and 0.28 +/-
      0.14 quality-adjusted life years vs. glimepiride, and 0.19 +/- 0.15 and 0.31 +/-
      0.15 quality-adjusted life years vs. sitagliptin, and was associated with higher
      costs of L 3003 +/- L 678 and L 4688 +/- L 639 vs. glimepiride, and L 1842 +/- L
      751 and L 3224 +/- L 683 vs. sitagliptin, over a patient's lifetime. Both
      liraglutide doses were cost-effective, with incremental cost-effectiveness ratios
      of L 9449 and L 16,501 per quality-adjusted life year gained vs. glimepiride, and
      L 9851 and L 10,465 per quality-adjusted life year gained vs. sitagliptin,
      respectively. CONCLUSIONS: Liraglutide, added to metformin monotherapy, is a cost
      effective option for the treatment of Type 2 diabetes in a UK setting.

PMID- 21883439
TI  - Oral contraception enhances growth hormone responsiveness to hyper- and
      hypoglycaemia.
AB  - AIMS: Plasma glucose levels influence growth hormone concentrations. Oral
      contraceptives are known to affect circulating growth hormone levels and glucose
      metabolism. While growth hormone plays an important role in hypoglycaemia counter
      regulation, it has been shown that oral contraceptives increase growth hormone
      concentrations. In this context, we tested if serum growth hormone concentrations
      display a differential response on glycaemic variations in healthy women using
      oral contraceptives and those not using contraceptives. METHODS: Fifteen healthy
      women with oral contraceptive treatment and 10 without participated in a stepwise
      hyper- and hypoglycaemic glucose clamp procedure. Serum growth hormone
      concentrations were measured at euglycaemic baseline and subsequently at plasma
      glucose plateaus of 8.8, 6.8, 4.8 and 2.8 mmol/l. RESULTS: Growth hormone values
      were significantly higher in women using oral contraceptives throughout the
      experiments (P = 0.001). Hyperglycaemia decreased growth hormone concentrations
      in women using oral contraceptives (P = 0.009), but not in those who were not
      using oral contraceptives (P = 0.241). Hypoglycaemia significantly elevated
      growth hormone concentrations in women using oral contraceptives (P = 0.009), but
      not in those not using oral contraceptives (P = 0.094). Maximum growth hormone
      values were reached at the end of the hypoglycaemic plateau, with significantly
      higher concentrations in the group using oral contraceptives than in the group
      not using oral contraceptives (P = 0.016). CONCLUSION: Healthy women on oral
      contraceptive treatment display an increased responsiveness of growth hormone to
      hypoglycaemic, as well as hyperglycaemic conditions and generally higher serum
      growth hormone concentrations than women without oral contraceptives. Given the
      known boosting effects of growth hormone on hypoglycaemic hormonal counter
      regulation, oral contraceptives may thus be a pharmacological candidate
      contributing to combat hypoglycaemia unawareness in women with diabetes in the
      future.

PMID- 21883440
TI  - Effect of psychological stress on glucose control in patients with Type 2
      diabetes.
AB  - AIM: To investigate the effect of acute psychological stress on glucose
      concentrations in patients with Type 2 diabetes, in the fasting state as well as
      in the postprandial state. METHODS: Thirty patients (12 female) with Type 2
      diabetes were included. Mean +/- SD age was 60 +/- 12 years, BMI 28.8 +/- 4.2
      kg/m(2), diabetes duration 8.9 +/- 6.7 years and HbA(1c) 51 +/- 9 mmol/mol (6.8
      +/- 0.8%). Using a non-randomized approach, all participants were exposed to
      moderate psychological stress by means of the Trier Social Stress Test: 10
      participants in the fasting state and 20 participants 75 min after intake of a
      standard meal. Blood pressure, heart rate and salivary cortisol were monitored on
      the control day and the stress-test day. Glucose concentrations were assessed
      using a continuous glucose monitoring system. RESULTS: On the stress-test day,
      blood pressure rose from 117/73 +/- 13/12 to 155/92 +/- 22/14 mmHg, heart rate
      from 77 +/- 11 to 91 +/- 25 b min(-1) and salivary cortisol concentrations from
      8.5 +/- 3.7 to 26.4 +/- 12.1 nmol/l (P < 0.001); these measurements remained
      unchanged on the control day. On the stress-test day, when the Trier Social
      Stress Test was applied 75 min after the intake of a standard meal, the glucose
      concentrations were significantly higher compared with the control day (mean
      difference 1.5 mmol/l, 95% CI 0.5-2.4, P = 0.003). In the fasting state, glucose
      concentrations slightly decreased during the control day but remained stable on
      the stress-test day (mean difference compared with the control day 0.7 mmol/l,
      95% CI -0.7 to 2.0, P = 0.31). CONCLUSIONS: When stress is experienced in the
      postprandial period, acute psychological stress significantly increases glucose
      concentrations in patients with Type 2 diabetes.

PMID- 21883441
TI  - Assessment of the under-reporting of diabetes in hospital admission data: a study
      from the Scottish Diabetes Research Network Epidemiology Group.
AB  - AIMS: Good quality data are required to plan and evaluate diabetes services and
      to assess progress against targets for reducing hospital admissions and bed days.
      The aim of this study was to assess the completeness of recording of diabetes in
      hospital admissions using recent national data for Scotland. METHODS: Data
      derived from linkage of the Scottish National Diabetes Register and hospital
      admissions data were analysed to assess the completeness of coding of diabetes in
      hospital inpatient admissions between 2000 and 2007 for patients identified with
      diabetes prior to hospital admission. RESULTS: In 2007, only 59% of hospital
      inpatient admissions for people previously diagnosed with diabetes mentioned
      diabetes, whereas over 99% of people with a mention of diabetes on hospital
      records were included in the diabetes register. The completeness of diabetes
      recording varied from 44 to 82% among mainland National Health Service Boards and
      from 34 to 89% among large general hospitals. Completeness of recording of
      diabetes as a co-morbidity also varied by primary diagnosis: 70 and 41% of
      admissions with coronary heart disease and cancer as the primary diagnosis
      mentioned co-existing diabetes, respectively. CONCLUSIONS: There is wide
      variation in the completeness of recording of diabetes in hospital admission
      data. Hospital data alone considerably underestimate the number of admissions and
      bed days but overestimate length of stay for people with diabetes. Linkage of
      diabetes register data to hospital admissions data provides a more accurate
      source for measuring hospital admissions among people diagnosed with diabetes
      than hospital admissions data.

PMID- 21883442
TI  - Stem cell-based treatments for Type 1 diabetes mellitus: bone marrow, embryonic,
      hepatic, pancreatic and induced pluripotent stem cells.
AB  - Type 1 diabetes mellitus--characterized by the permanent destruction of insulin
      secreting beta-cells--is responsive to cell-based treatments that replace lost
      beta-cell populations. The current gold standard of pancreas transplantation
      provides only temporary independence from exogenous insulin and is fraught with
      complications, including increased mortality. Stem cells offer a number of
      theoretical advantages over current therapies. Our review will focus on the
      development of treatments involving tissue stem cells from bone marrow, liver and
      pancreatic cells, as well as the potential use of embryonic and induced
      pluripotent stem cells for Type 1 diabetes therapy. While the body of research
      involving stem cells is at once promising and inconsistent, bone marrow-derived
      mesenchymal stem cell transplantation seems to offer the most compelling evidence
      of efficacy. These cells have been demonstrated to increase endogenous insulin
      production, while partially mitigating the autoimmune destruction of newly formed
      beta-cells. However, recently successful experiments involving induced
      pluripotent stem cells could quickly move them into the foreground of therapeutic
      research. We address the limitations encountered by present research and look
      toward the future of stem cell treatments for Type 1 diabetes.

PMID- 21883443
TI  - Re-examining a measure of diabetes-related burden in parents of young people with
      Type 1 diabetes: the Problem Areas in Diabetes Survey - Parent Revised version
      (PAID-PR).
AB  - AIMS: In a pediatric patients, the burden of diabetes lies within the family. In
      the current era of intensive insulin therapy, perceived parental burden may
      affect the family's efforts at effective diabetes management. The aims of this
      study were to re-examine and revise a measure of perceived parental burden
      associated with caring for a child with diabetes in the current era. METHODS: A
      geographically diverse population of young people (N = 376) with Type 1 diabetes
      and their parents included participants in the Juvenile Diabetes Research
      Foundation continuous glucose monitoring study and patients from the Joslin
      Diabetes Center. Participants provided data on demographics, diabetes management,
      diabetes-specific family conflict, and quality of life at baseline and after 6
      months of follow-up. RESULTS: Young people were 12.9 +/- 2.7 years old with
      diabetes duration of 6.3 +/- 3.5 years. Mean HbA(1C) was 8.0 +/- 1.2%(64
      mmol/mol), 58% received insulin pump therapy, and young people monitored blood
      glucose 5.2 +/- 2.3 times/day. Factor analysis yielded two factors, 'Immediate
      Burden' and 'Theoretical Burden'. The Problem Areas in Diabetes Survey - Parent
      Revised version (PAID-PR) demonstrated excellent internal consistency (Cronbach's
      alpha = 0.87; factor 1 alpha = 0.78; factor 2 alpha = 0.83). Greater parental
      burden was associated with more frequent blood glucose monitoring, higher HbA(1C)
      levels, greater diabetes-specific family conflict, and lower quality of life.
      Test-retest analysis was acceptable (r = 0.62). CONCLUSIONS: The PAID-PR
      demonstrated excellent internal consistency, good test-retest reliability, and
      associations with diabetes-specific family conflict and quality of life. This
      brief measure may have both clinical and research utility in the management of
      young people with Type 1 diabetes.

PMID- 21883444
TI  - Melatonin protects against rotenone-induced cell injury via inhibition of Omi and
      Bax-mediated autophagy in Hela cells.
AB  - Parkinson's disease is the second most common neurodegenerative disease, and
      environmental toxins such as rotenone play an important role in causing
      degeneration of dopaminergic neurons. Melatonin, a major secretory product of
      pineal, is recently reported to protect against rotenone-induced cell death in
      animal models. Yet, the mechanism involved in this protection needs to be
      elucidated. Here, we report that rotenone treatment (0-100 MUM) decreased cell
      survival of Hela cells in a dose-dependent manner. At concentrations ranging from
      0.1 to 100 MUM, rotenone induced a dose-dependent increase in the expression of
      microtubule-associated protein 1 light chain 3 (LC3)-II, a protein associated
      with the autophagosomal membrane. Knockdown of Bax or Omi using shRNA inhibited 1
      MUM rotenone-induced autophagy. To determine whether melatonin would protect
      cells against rotenone-induced cell death and autophagy, we pretreated Hela cells
      with 250 MUM melatonin for 24 hr in the presence of rotenone. Melatonin inhibited
      Bax expression and the release of the omi/HtrA2 into the cytoplasm induced by 1
      MUM rotenone. Melatonin 250 MUM treatment also suppressed cell death induced by
      0.1-100 MUM rotenone and protected against the formation of LC3-II in cells
      exposed to 1 MUM rotenone. This work demonstrates a novel role for melatonin as a
      neuroprotective agent against rotenone.

PMID- 21883445
TI  - Melatonin improves glucose homeostasis in young Zucker diabetic fatty rats.
AB  - The aim of this study was to investigate the effects of melatonin on glucose
      homeostasis in young male Zucker diabetic fatty (ZDF) rats, an experimental model
      of metabolic syndrome and type 2 diabetes mellitus (T2DM). ZDF rats (n=30) and
      lean littermates (ZL) (n=30) were used. At 6wk of age, both lean and fatty
      animals were subdivided into three groups, each composed of ten rats: naive (N),
      vehicle treated (V), and melatonin treated (M) (10mg/kg/day) for 6wk. Vehicle and
      melatonin were added to the drinking water. ZDF rats developed DM (fasting
      hyperglycemia, 460+/-39.8mg/dL; HbA(1) c 8.3+/-0.5%) with both insulin resistance
      (HOMA-IR 9.28+/-0.9 versus 1.2+/-0.1 in ZL) and decreased beta-cell function
      (HOMA1-%B) by 75%, compared with ZL rats. Melatonin reduced fasting hyperglycemia
      by 18.6% (P<0.05) and HbA(1) c by 11% (P<0.05) in ZDF rats. Also, melatonin
      lowered insulinemia by 15.9% (P<0.05) and HOMA-IR by 31% (P<0.01) and increased
      HOMA1-%B by 14.4% (P<0.05). In addition, melatonin decreased hyperleptinemia by
      34% (P<0.001) and raised hypoadiponectinemia by 40% (P<0.001) in ZDF rats.
      Moreover, melatonin reduced serum free fatty acid levels by 13.5% (P<0.05). These
      data demonstrate that oral melatonin administration ameliorates glucose
      homeostasis in young ZDF rats by improving both insulin action and beta-cell
      function. These observations have implications on melatonin's possible use as a
      new pharmacologic therapy for improving glucose homeostasis and of obesity
      related T2DM, in young subjects.

PMID- 21883446
TI  - Biomarkers and special features of oxidative stress in the anterior segment of
      the eye linked to lens cataract and the trabecular meshwork injury in primary
      open-angle glaucoma: challenges of dual combination therapy with N
      acetylcarnosine lubricant eye drops and oral formulation of nonhydrolyzed
      carnosine.
AB  - The implication of oxidative stress associated with increased oxidant production
      in mammalian and human cells characterized by the release of free radicals,
      resulting in cellular degeneration, is involved in many ocular diseases, such as
      age-related macular degeneration, retinopathy of prematurity, retinal light
      damage, primary open-angle glaucoma (POAG), and cataract. Cataract is the leading
      cause of blindness, accounting for 50% of blindness worldwide. Glaucoma, the
      leading cause of irreversible blindness, is considered as a progressive optic
      neuropathy often caused by elevated intraocular pressure (IOP) consequent to
      abnormally high resistance to aqueous humor (AH) drainage via the trabecular
      meshwork (TM) and Schlemm's canal. Morphological and biochemical analyses of the
      TM of patients with POAG revealed the loss of cells, increased accumulation of
      extracellular matrix proteins (ECM), changes in the cytoskeleton, cellular
      senescence, and the process of subclinical inflammation. The TM is the target
      tissue of glaucoma in the anterior chamber, and the development and progression
      of glaucoma are accompanied by the accumulation of oxidative damage in this
      tissue. The separate studies were conducted to comparatively evaluate the
      sensitivity to oxidative stress and lipid peroxidation (LPO) of anterior chamber
      tissues including TM. Accumulation of the primary, secondary, and end products of
      LPO (diene and triene conjugates, Schiff's bases) was noted in the studied
      extracts. Significant differences in the levels of all mentioned LPO products in
      comparison with the control were observed. The data may be considered as an
      evidence of LPO participation in the destruction of the trabecule and Schlemm's
      canal in POAG. Treatment of TM cells with oxidative stress induced POAG-typical
      changes such as ECM accumulation, cell death, disarrangement of the cytoskeleton,
      advanced senescence, and the release of inflammatory markers. By pretreatment
      with antioxidants, prostaglandin analogs, beta-blockers, or local carbonic
      anhydrase inhibitors, these effects were markedly reduced. Oxidative stress can
      induce characteristic glaucomatous TM changes, and these oxidative stress-induced
      TM changes can be minimized by the use of antioxidants and IOP-lowering
      substances. It is tempting to speculate that the prevention of oxidative stress
      exposure to the TM may help to reduce the progression of POAG. The author's
      laboratory has developed and patented the dual combination therapy with N
      acetylcarnosine lubricant eye drops and oral formulation of nonhydrolyzed
      carnosine in ripe cataracts and POAG. The specific regimen for the treatment in
      each stage of age-related ophthalmic disease has been taken up. In the treatment
      of POAG, this dual therapy can be combined with conventional antiglaucoma therapy
      with beta-blocking and/or adrenergic agonist medicines providing the significant
      IOP-lowering effect and significant increase in outflow facility. The developed
      therapy is a prominent management care of the glaucomatous neurodegeneration.

PMID- 21883447
TI  - New anticoagulants for the prevention of stroke in atrial fibrillation.
AB  - Oral anticoagulation in atrial fibrillation is obligatory to lower the risk of
      spontaneous cerebrovascular and systemic thromboembolism. For this purpose,
      vitamin K antagonists (coumarins) have been recommended as the most effective
      drugs for a long time. However, problems with the practical use of these agents,
      e.g. the need for frequent and regular coagulation controls, the inter-individual
      differences in maintaining a stable therapeutic range, as well as drug or food
      interactions, have led to the search and investigation of alternative compounds
      characterized by a more simple use (e.g. without regular controls of therapeutic
      levels), high efficacy, as well as low risk of bleeding. The direct thrombin
      inhibitor dabigatran and the direct factor Xa inhibitors rivaroxaban and apixaban
      have recently been investigated to prove whether they fulfill the high expectancy
      of an ideal anticoagulant with respect to a more favorable efficacy/safety
      profile and without the need for coagulation controls, thereby improving quality
      of life. Dabigatran (RE-LY) achieved an impressive reduction in stroke and non
      central nervous system (non-CNS) embolism (110 mg: 1.5%/year; 150 mg: 1.1%/year)
      in contrast to warfarin (1.7%/year; P = 0.34 and P < 0.001) with a favorable
      action on bleeding hazards. The results of rivaroxaban which were obtained in the
      ROCKET AF study (on treatment analysis: stroke and non-CNS embolism: 1.7%/year
      vs. 2.15%/year with warfarin; P = 0.015; primary safety endpoint major and minor
      bleeding: 14.91 vs. 14.52%; P = 0.442) point in the same direction. And finally,
      compared to aspirin, apixaban reduced the combined primary efficacy endpoint by
      52% with comparable rates of bleeding (AVERROES). This review gives a summary of
      the current knowledge about these agents and their potential future importance.

PMID- 21883448
TI  - Management of Group B streptococcal sepsis risk in well, term newborns.
AB  - AIM: To investigate how clinically well, term newborns at risk of early-onset
      Group B streptococcal (EOGBS) disease are currently managed in the United Kingdom
      (UK). METHODS: Review of guidelines of UK neonatal units. RESULTS: One hundred
      and twenty-five guidelines covering 157 neonatal units were received (71% of UK
      units), three of which were excluded from the review. We found great variation in
      every aspect for the management of EOGBS disease risk including the following:
      definition of risk factors; management of at-risk newborns; choice of
      antibiotics. CONCLUSION: Our findings highlight the need for national consensus
      guidelines and clinical trials into the management of risk babies at risk of
      EOGBS disease.

PMID- 21883449
TI  - The association of childhood iron deficiency anaemia with severe dental caries.

PMID- 21883451
TI  - Build our youth for the future in paediatrics and beyond.

PMID- 21883450
TI  - Development of smooth pursuit eye movements in very preterm born infants: 3.
      Association with perinatal risk factors.
AB  - AIM: To investigate the association between perinatal risk factors and neonatal
      complications and early oculo-motor development in very preterm infants. METHODS:
      Perinatal risk factors were identified, and the potential association with early
      oculo-motor development was evaluated by measuring smooth pursuit eye movements
      (SP) at 2 and 4 months' corrected age (CA) in a population of very preterm
      infants born in Uppsala County 2004-2007 (n = 113). RESULTS: Among the 15 tested
      factors, eight showed significant association in univariate analysis with lower
      levels of SP at 4 months' CA, namely administration of prenatal corticosteroids,
      gestational age, birthweight, bronchopulmonary dysplasia, retinopathy of
      prematurity, periventricular leukomalacia, intraventricular haemorrhage >grade 2,
      and persistent ductus arteriosus. At 2 months' CA, only retinopathy of
      prematurity >stage 2 was associated with lower levels of SP. When all factors
      significant in the univariate tests were included in multiple regressions aimed
      to assess each factor's independent relation to SP, periventricular leukomalacia
      was the only significant independent factor. When adding 2-5 of the significant
      factors using multiple regression analysis, the levels of SP became lower.
      CONCLUSION: Perinatal risk factors were associated with lower levels of SP. This
      could be interpreted as delayed or disturbed development of normal oculomotor
      ability.

PMID- 21883452
TI  - Paradigm shift in consciousness research: the child's self-awareness and
      abnormalities in autism, ADHD and schizophrenia.
AB  - Self-awareness is a pivotal component of any conscious experience and conscious
      self-regulation of behaviour. A paralimbic network is active, specific and causal
      in self-awareness. Its regions interact by gamma synchrony. Gamma synchrony
      develops throughout infancy, childhood and adolescence into adulthood and is
      regulated by dopamine and other neurotransmitters via GABA interneurons. Major
      derailments of this network and self-awareness occur in developmental disorders
      of conscious self-regulation like autism, attention deficit hyperactivity
      disorder (ADHD) and schizophrenia. CONCLUSION: Recent research on conscious
      experience is no longer limited to the study of neural 'correlations' but is
      increasingly lending itself to the study of causality. This paradigm shift opens
      new perspectives for understanding the neural mechanisms of the developing self
      and the causal effects of their disturbance in developmental disorders.

PMID- 21883453
TI  - Serum screening for detection of high-risk group for early-stage diffuse type
      gastric cancer in Japanese.
AB  - BACKGROUND AND AIM: Serum screening systems are beneficial for gastric cancer
      mass surveys; however, the marker for diffuse type gastric cancer (DGC) is not
      defined. We attempted to define the high-risk group for DGC by using serum
      markers of anti-Helicobacter pylori antibody and pepsinogens (PG). METHODS: Forty
      two patients in the early stage of DGC and 511 controls were enrolled. Fasting
      serum samples were collected, and anti-H. pylori antibody and PG were evaluated.
      The risk for DGC was calculated. RESULTS: The prevalence of DGC was higher in H.
      pylori-positive patients (odds ratio [OR] = 4.3 in men, 9.6 in women). DGC
      prevalence was significantly higher in the PG1+ group in women (OR = 10.7);
      however, it was lower in the PG3+ group in both men and women. Patients with PG
      II >= 30 revealed a significantly higher risk for DGC. By combining factors,
      higher OR (OR = 12.5 in men, 42.7 in women) were obtained when we defined the
      risk group as H. pylori-positive, PG-negative, and having PG II >= 30.
      CONCLUSION: The risk group for DGC can be defined by evaluating ordinary serum
      gastritis markers.

PMID- 21883454
TI  - Transitional features of histologic type of non-alcoholic fatty liver disease in
      Korean young men.
AB  - BACKGROUND AND AIM: The prevalence of non-alcoholic fatty liver disease (NAFLD)
      is increasing in Korea as the dietary pattern and lifestyle become more
      Westernized and the obese population increases. The spectrum of NAFLD ranges from
      asymptomatic steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis.
      Schwimmer et al. divided NASH into three types according to the histological
      characteristics, such as adult type, pediatric type and overlap type. We
      investigated clinical and histologic features of NAFLD patients in Korean young
      men. METHODS: A total of 64 male patients under age 30 years, diagnosed as NAFLD
      by a liver biopsy, were reviewed retrospectively. NASH was diagnosed by NAFLD
      activity score (NAS), and NASH patients were classified with Schwimmer's
      histological classification. RESULTS: Pathological features of liver biopsy
      revealed NASH in most cases (59 cases, 92.2%) including 29 cases (45.3%) of
      borderline NASH and 30 cases (46.9%) of definite NASH. The definite NASH group
      showed significantly high aspartate aminotransferase/alanine aminotransferase
      levels compared to the borderline NASH group. There were four cases (6.8%) of
      pediatric type, 17 cases (28.8%) of adult type, and 38 cases (64.4%) of overlap
      type in the NASH group. NAS was 3.75 +/- 0.05 in the pediatric type, 4.29 +/-
      1.16 in the adult type and 4.87 +/- 1.21 in the overlap type, and the overlap
      type showed a higher NAS than the pediatric type. The fibrosis stage was
      significantly higher in the overlap type than the other types. CONCLUSION: Most
      Korean young men with NAFLD turned out to have borderline or definite NASH. More
      than half of the NASH cases showed overlap type in Korean young men.

PMID- 21883455
TI  - DR-70 immunoassay for the surveillance of hepatocellular carcinoma.
AB  - BACKGROUND AND AIM: Although alpha-fetoprotein (AFP) is a widely used serological
      marker for hepatocellular carcinoma (HCC), its utility is limited due to its
      unsatisfactory sensitivity. Meanwhile, a newly developed immunoassay-DR-70-has
      been reported to have a good sensitivity for HCC in a small-scale study. The aim
      of this study was to determine the clinical value of DR-70 for the surveillance
      of HCC. METHODS: Serum levels of DR-70 and AFP were measured in 103 patients with
      HCC, 50 healthy volunteers, and 33 patients with chronic liver disease. In
      addition, we investigated the prognostic value of DR-70 in patients with HCC
      correlating with the clinical staging-Cancer of the Liver Italian Program (CLIP)
      score and Barcelona Clinic Liver Cancer (BCLC) classification. RESULTS: Based on
      the receiver operating characteristic curve with area under the curve of 0.836,
      the DR-70 cut-off value for detecting HCC was determined to be 0.75 ug/mL. DR-70
      provided a sensitivity of 81.6% and a specificity of 77.1%, and correlated well
      with the CLIP score and BCLC classification. The combination of DR-70 and AFP
      increased the sensitivity to 91.2%. The prognosis for patients with HCC with DR
      70 level > 0.75 ug/mL was worse than that for those with DR-70 <= 0.75 ug/mL.
      Among the patients with early stage HCC (CLIP score 0-2), DR-70 > 0.75 ug/mL
      independently predicted a poor survival. CONCLUSIONS: DR-70 immunoassay is
      complementary to AFP for the detection of HCC and has a good correlation with
      clinical staging and prognosis.

PMID- 21883456
TI  - Giant intrapericardial lipoma.

PMID- 21883457
TI  - The transseptal approach to the mitral valve during multivalvular surgery.
AB  - AIM: We investigated the short and mid-term outcome of the transseptal approach
      to the mitral valve during multivalvular surgery. METHODS: Within a three-year
      period ending in May 2010, we used the transseptal approach in performing mitral
      valve surgery in 62 patients. Procedures performed were: mitral valve replacement
      and tricuspid annuloplasty in 40 patients, both aortic and mitral valve
      replacement with tricuspid annuloplasty in 13 patients, mitral valve and
      tricuspid valve replacement in eight patients and mitral valve repair and
      tricuspid annuloplasty in addition to coronary artery bypass surgery in one
      patient. RESULTS: There were no complications associated with the transseptal
      approach. There were no conduction abnormalities, nor were there any procedure
      related deaths. CONCLUSION: We conclude that use of the transseptal approach for
      mitral valve operations is simple and safe in patients necessitating right
      atriotomy for concomitant procedures. 

PMID- 21883458
TI  - Comparison of the tear film clinical parameters at two different times of the
      day.
AB  - PURPOSE: The aim of the present study was to analyse the quality and quantity of
      the tear film in a young, healthy and non-contact lens-wearing population with
      measurements taken in the morning and in the afternoon to establish if changes
      exist in these parameters. METHODS: In a controlled laboratory setting, morning
      and afternoon clinical parameters of tear film were assessed. Schirmer test, tear
      meniscus height, break-up time and non-invasive break-up time were measured in 51
      normal subjects on the same day for each individual. RESULTS: Tear volume showed
      no significant changes during the day but tear film stability was significantly
      reduced at the end of the day (p < 0.001), demonstrating that tear film stability
      is affected by the time of day. CONCLUSION: Researchers and clinicians might wish
      to consider these differences when comparisons are made between studies and
      populations and also when the same patient is observed over periods. Fluorescein
      instillation can affect the measurements of tear stability in subjects with poor
      quality tear film.

PMID- 21883459
TI  - The Alfieri stitch: the advantages for mitral valve repair in difficult
      circumstances.
AB  - In certain complex cases, where there is severe calcification of the mitral
      annulus but significant mitral regurgitation or systolic anterior motion (SAM),
      or in high-risk cases where prolonged bypass is to be avoided, the Alfieri-stitch
      repair of the mitral valve may be the most appropriate option available,
      particularly as it can be performed quickly through the aortic valve. We describe
      three cases undergoing aortic valve replacement, in which this technique was
      successfully applied in patients in whom more conventional repair techniques or
      valve replacement would have been hazardous, due to annular calcification and
      patient frailty. 

PMID- 21883460
TI  - Repair of left atrial-esophageal fistula following percutaneous radiofrequency
      ablation for atrial fibrillation.
AB  - Atrial-esophageal fistula is a rare but often fatal complication of percutaneous
      radiofrequency ablation for atrial fibrillation. We present a patient who was
      diagnosed with this complication in a delayed fashion and successfully treated
      with primary repair via left thoracotomy. The details of the surgical approach
      are discussed. 

PMID- 21883461
TI  - Repair of pulmonary artery aneurysms.
AB  - BACKGROUND AND AIM OF THE STUDY: We have presented the results of pulmonary
      arterial aneurysm repairs performed over eight years. METHODS: From 2002 to
      December 2010, we performed nine operations for pulmonary artery aneurysms in our
      department. The mean age of the patients was 37.8 +/- 17.1 years and four were
      females. Five patients had pulmonic valve stenosis, three patients had
      concomitant pathologies on the aortic or mitral valves, and two had isolated
      pulmonary arterial aneurysm. Aneurysm repairs were performed by plication in
      eight patients and with Dacron patch repair in one patient. RESULTS: There were
      no postoperative deaths. Three patients required inotropic support
      postoperatively. One patient had pulmonary morbidity. The results of the
      pathology revealed intimal hyalinization, edema, and elastic fiber degeneration
      in the media, fibrosis in the adventitia, and increased vascularity. All patients
      were in New York Heart Association Class I or II except for one patient who had a
      prolonged intensive care stay. The mean duration of follow-up was 48.6 +/- 33.2
      months (range, 2 to 107) adding up to a total of 36.4 patient/years. The mean
      diameter of the pulmonary artery in the recent imaging was 3.6 +/- 0.4 cm.
      CONCLUSION: Pulmonary artery aneurysms are rare entities which are usually
      associated with other congenital defects. While surgery is the preferred
      treatment for symptomatic aneurysms, controversy exists as to the indications for
      repair in asymptomatic patients. 

PMID- 21883462
TI  - Scimitar syndrome: a complex form of anomalous pulmonary venous return.
AB  - Scimitar syndrome, or pulmonary venolobar syndrome, is a rare congenital anomaly,
      in which all the right pulmonary veins drain into the inferior vena cava. In this
      study, we review the diagnostic features, clinical management, and surgical
      strategy in the Scimitar syndrome and discuss the significance of new generation
      diagnostic imaging methods for this rare anomaly. 

PMID- 21883463
TI  - Mechanical circulatory support as a bridge to transplant candidacy.
AB  - INTRODUCTION: The use of mechanical circulatory support (MCS) in nontransplant
      eligible candidates remains controversial. Our decision to offer MCS for
      nontransplant candidates has led to their reevaluation after a period of left
      ventricular assist device (LVAD) support. METHODS: From 2001 to September 2009,
      we had 37 patients who received an implantable LVAD, 22 (59%) were not deemed to
      be transplant eligible at the time of LVAD insertion (bridge to candidacy, BTC
      group). RESULTS: Fifteen (41%) patients were considered transplant eligible
      (bridge to transplant, BTT group) at the time of device insertion and received a
      HeartMate XVE (n = 7), HeartMate 2 (n = 7), or a Novacor LVAS (n = 1). In the BTC
      group, patients received the HeartMate XVE device (n = 11), HeartMate 2 (n = 5),
      or the Novacor LVAS (n = 6). The primary criterion for transplant ineligibility
      was refractory pulmonary hypertension (PH) in 18 patients, 3 patients did not
      meet our body mass index criteria (>35 kg/m(2)), and 2 patients were dialysis
      dependent. Six (27%) BTC patients died on support. Overall, 16/22 patients (73%)
      were subsequently listed for transplantation, with one listed for combined heart
      lung due to refractory PH. Twelve patients (75%) underwent successful heart
      transplantation. Three patients died during their transplant. Overall
      posttransplant survival at one year shows lower survival in the BTC group
      compared to the BTT group (67% vs. 100%, p = 0.05). At two years and three years
      the survival was lower, but not statistically different (BTC vs. BTT: 67% vs. 90%
      and 64% vs. 87%, respectively, p = NS). CONCLUSIONS: MCS can successfully convert
      a large proportion of transplant-ineligible patients into acceptable candidates. 

PMID- 21883464
TI  - Aneurysmal circumflex aortic arch.
AB  - Circumflex aortic arch aneurysm is a rare condition. We report a 9-year-old
      female with this anomaly who underwent resection of the aneurysmal segment and
      reconstruction of aortic arch anterior to trachea under cardiopulmonary bypass
      and deep hypothermic circulatory arrest. The patient was completely relieved of
      dysphagia and recovered without any cardiac or neurological sequelae. 

PMID- 21883465
TI  - Predictors of occupancy trend across spatial scale.
AB  - Many explorations of extinction probability have had a global focus, yet it is
      unclear whether variables that explain the probability of extinction at large
      spatial extents are the same as those at small spatial extents. Thus, we used
      nearly annual presence-absence records for the most recent 40 years of a 110-year
      data set from Palenque, Mexico, an area with ongoing deforestation, to explore
      which of >200 species of birds have probabilities of extirpation that are likely
      to increase. We assessed associations between long-term trends in species
      presence (i.e., detection in a given year) and body size, geographic range size,
      diet, dependence on forest cover, taxonomy, and ecological specialization. Our
      response variable was the estimated slope of a weighted logistic regression for
      each species. We assessed the relative strength of each predictor by means of a
      model ranking scheme. Several variables associated with high extinction
      probability at global extents, such as large body size or small geographic range
      size, were not associated with occurrence of birds over time at our site. Body
      size was associated with species loss at Palenque, but occurrence trends of both
      very large and very small species, particularly the latter, have declined, or the
      species have been extirpated. We found no association between declining
      occurrence trend and geographic range size, yet decline correlated with whether a
      species depends on forest (mean occupancy trend =-0.0380, 0.0263, and 0.0186 for,
      respectively, species with high, intermediate, or low dependence on forest) and
      with complex combinations of diet and foraging strata (e.g., occurrence of canopy
      insectivores and terrestrial omnivores has increased, whereas occurrence of mid
      level frugivores and terrestrial granivores has decreased). Our findings
      emphasize that analyses of local areas are necessary to explicate extirpation
      risk at various spatial extents.

PMID- 21883466
TI  - Thrombectomy of prosthetic dialysis grafts using mechanical plus "no-wait lysis"
      approach requires less procedure time and radiation exposure.
AB  - In spite of the existence of various strategies, dialysis graft thrombectomy
      remains time-consuming and requires substantial radiation exposure. The authors
      report a new approach for graft thrombectomy, "no-wait lysis", with the objective
      to examine its effect on procedure time and radiation exposure. Based on the use
      of tissue plasminogen activator (tPA), the 88 retrospectively reviewed graft
      thrombectomies were divided into "no-tPA" group (n = 35) and "no-wait lysis"
      group (n = 53). Fogarty thrombectomy and balloon angioplasty were used similarly
      in both groups. In the "no-wait lysis" group, small-dose tPA was added directly
      into the graft during the procedure. Comparing the "no-wait lysis" group with the
      "no-tPA" group, the procedure time was reduced: 27.2 +/- 10.2 vs. 55.5 +/- 19.9
      minutes (p < 0.0001), and the radiation exposure time was decreased
      correspondingly: 159.4 +/- 61.6 vs. 243.9 +/- 101.9 seconds (p < 0.0001).
      Multivariate regression analysis revealed that the use of "no-wait lysis"
      approach was the major significant predictor for shorter procedure time and
      radiation exposure time. In conclusion, our data support that the use of "no-wait
      lysis" approach for dialysis graft thrombectomy substantially reduces procedure
      time and radiation exposure, and it may serve as an efficient and economical
      alternative to other existing approaches.

PMID- 21883467
TI  - Vascular access.

PMID- 21883468
TI  - Blood pressure management.

PMID- 21883469
TI  - Decolonization to prevent infections with Staphylococcus aureus in patients
      undergoing hemodialysis: a review of current evidence.
AB  - Staphylococcus aureus infections remain common in patients undergoing
      hemodialysis, and the consequences of these infections are potentially severe.
      Although a number of evidence-based practices have been shown to decrease the
      healthcare-associated infections that this organism can cause, many questions
      remain about the utility of decolonization as a mechanism to prevent these
      infections. This brief review describes the current epidemiology of S.aureus
      infections in patients undergoing hemodialysis and reviews the evidence
      surrounding decolonization as an infection prevention strategy.

PMID- 21883470
TI  - The predictive value and evolution of N-terminal pro-B-type natriuretic peptide
      levels following transcutaneous aortic valve implantation.
AB  - AIMS: We sought to define the predictive value and evolution of N-terminal pro-B
      type natriuretic peptide (NT-proBNP) levels following transcutaneous aortic valve
      implantation (TAVI). METHODS AND RESULTS: We investigated 91 consecutive patients
      who underwent TAVI (59 transfemoral [TF], 32 transapical [TA]) in our
      institution. The balloon-expandable valve was implanted in 75 and the self
      expanding in 16 patients. The baseline (within 48 hours prior to procedure),
      early (24-74 hours), and late (3-12 months) postprocedural NT-proBNP levels were
      determined. The mortality status of all patients was ascertained as of September
      2010. The 30-day and 1.3(mean)-year mortality was 3% and 12% (2%, 9% in the TF
      and 6%, 19% in the TA group). Increased baseline (chi(2) = 5.9, P = 0.016) and
      early (chi(2) = 4.9, P = 0.028) NT-proBNP levels were predictive of mortality.
      All decrements of the NT-proBNP levels in the TF patients were significant
      (baseline 4,984 +/- 8,106 vs. early 3,912 +/- 6,551 pg/mL, P = 0.016; late 633 +/
      606 pg/mL, P = 0.003). In contrast, there was a trend for the early levels to
      increase in the TA patients (6,423 +/- 8,897 vs. 8,100 +/- 10,178 pg/mL, P =
      0.090), and a significant decline in the late levels as compared to baseline
      (1,704 +/- 3,417 pg/mL, P = 0.005). CONCLUSION: NT-proBNP levels are predictive
      of mortality following TAVI. There is a differential early evolution of their
      levels between the TF and TA patients and a significant decline later in both
      groups. 

PMID- 21883471
TI  - External side-compression of radial artery: a simple technique for successful
      advancement of guidewires through the radial approach.
AB  - BACKGROUND: The transradial approach has several pitfalls that include problems
      regarding the radial puncture and difficulties with the catheter technique. We
      evaluated whether external side-compression of radial artery was helpful to yield
      the success rate for advancement of guidewires under the presence of side
      branches or arterial tortuosity. METHODS AND RESULTS: The study population
      consisted of 11 patients with unsuccessful advancement of guidewires into the
      brachial artery. In 7 patients, the J-tip hydrophilic guidewire was not advanced
      into the brachial artery because it always directed into the side branch. During
      external side-compression of radial artery at the culprit site with a finger of
      the second operator, the guidewire was successfully advanced into the brachial
      artery in all patients. In 4 patients, the guidewire was not advanced into the
      brachial artery because the radial artery was tortuous. During external side
      compression of radial artery at the culprit site, the guidewire was successfully
      advanced into the brachial artery in 2 patients. In the remaining 2 patients in
      whom this attempt was unsuccessful, coronary angiography was performed through
      the right brachial artery. Overall success rate of this technique was 82%.
      CONCLUSION: External side-compression of radial artery is an easy and feasible
      technique for difficulties in the advancement of guidewires due to the presence
      of side branches or arterial tortuosity.

PMID- 21883472
TI  - A novel mortality risk score for female patients undergoing endovascular
      interventions.
AB  - BACKGROUND: Peripheral arterial disease (PAD) has been described as a rising
      epidemic in recent years. The majority of subjects studied in PAD literature have
      been male, leaving female patients an underrepresented population with regard to
      revascularization outcomes. The goal of our study was to determine the death rate
      and predictors of mortality in female patients undergoing endovascular
      intervention (EI) for symptomatic PAD. METHODS AND RESULTS: This study was
      conducted as a single-center retrospective chart review of 292 female patients
      who underwent EI for symptomatic PAD. Patient variables including demographics
      and procedural data were analyzed for statistical significance with regard to
      mortality. Age, history of congestive heart failure (CHF), and chronic kidney
      disease (CKD) were found to be significant predictors of mortality on
      multivariable analysis. A death risk score was formulated based on the above
      variables, risk stratifying patients into low, medium, or high risk groups for
      mortality after EI. Overall, 76 patients (26%) fell into the low risk category
      with a mortality of 5.3%, 102 patients (35%) fell into the moderate risk with a
      mortality of 15.7%, and 112 patients (39%) fell into the high-risk group with a
      mortality of 45.5% (P < 0.0001). CONCLUSIONS: Our study is the first of its kind
      to specify predictors of mortality in female patients with symptomatic PAD. This
      study also provides a tool to identify female PAD patients at high risk for death
      after EI. Finally, it highlights the effect of CKD, age, and CHF on mortality of
      patients with PAD. 

PMID- 21883473
TI  - Initial experience with a magnetic navigation system for invasive treatment in
      patients with non-ST-segment elevation acute coronary syndromes.
AB  - BACKGROUND: Magnetic navigation system (MNS) assisted percutaneous coronary
      intervention (MPCI) has been demonstrated an advantage over conventional PCI
      (CPCI) in complex lesions and tortuous vessels. However, the benefits of MNS in
      clinical unstable and vulnerable lesions were little studied. The aim of this
      study is to evaluate the feasibility and benefits of MPCI versus CPCI in patients
      with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS:
      Thirty-seven consecutive patients with NSTE-ACS undergoing MPCI were compared
      with 37 matched CPCI patients selected from the same concurrent database. Time to
      cross lesion, fluoroscopy time, and contrast usage to cross lesion were used as
      primary end-points. RESULTS: Of the 37 culprit lesions in MPCI, 36 were crossed
      successfully giving a success rate of 97.3%. The procedure and the fluoroscopy
      time to cross the lesion were similar between the magnetic and conventional PCI
      groups (82.0 +/- 67.9 seconds vs. 85.8 +/- 59.2 seconds, P = 0.692, and 62.6 +/-
      57.6 seconds vs. 65.4 +/- 49.5 seconds, P = 0.738, respectively). In Type A/B1
      lesions, there seemed no difference in contrast use (2.7 +/- 0.7 mL vs. 3.3 +/-
      0.9 mL, P = 0.284). But as lesion complexity increased from type B2 to C,
      significantly less contrast was needed in type B2 (5.1 +/- 2.6 mL vs. 7.9 +/- 4.0
      mL, P = 0.019) and type C (9.8 +/- 5.7 mL vs. 14.7 +/- 7.4 mL, P = 0.030). No
      major adverse cardiac events were observed in either the MPCI or CPCI group.
      CONCLUSIONS: MNS assisted technique appears to be feasible and effective in NSTE
      ACS patients with more complex lesions; however, it probably offers little
      benefit in simple lesions like ACC/AHA type A/B1. 

PMID- 21883474
TI  - Three-year clinical outcome with the EndeavorTM zotarolimus-eluting stent in
      primary percutaneous coronary intervention for ST elevation myocardial
      infarction: the EndeavorTM primary PCI study (E-PPCI).
AB  - Primary percutaneous coronary intervention (PPCI) is superior to thrombolysis in
      STEMI (ST segment elevation myocardial infarction) patients. Data on late stent
      thrombosis (ST) have raised concerns regarding the use of drug-eluting stents
      during PPCI. We report the first 3-year clinical evaluation of the zotarolimus
      eluting stent (ZES) in patients undergoing PPCI for STEMI, a single-center,
      prospective cohort study of consecutive patients admitted with STEMI. All
      underwent PPCI within 12 hours of symptoms; each received one or more ZES in one
      or more target lesions. All patients received aspirin 300 mg, clopidogrel 600 mg,
      abciximab, and unfractionated heparin. A total of 102 STEMI patients (76 male,
      mean 62 years) received 162 ZES (mean 1.6 stents/patient). Median call-to-balloon
      time was 123 (102-152) minutes. Thirty-day combined major adverse cardiovascular
      event (MACE) rate was 3.9% (n = 4). Subacute ST occurred in 2 patients (1.96%).
      Combined MACE rates at 12 months and 3 years were 7.8% (n = 8) and 13.7% (n =
      14). Late ST occurred in 1 patient (1%) with no occurrence of very late ST. This
      is the first 3-year report of the use of the ZES in an unselected, consecutive
      PPCI population. Overall 3-year incidence of MACE and target lesion
      revascularization (5.9%) was low, and was comparable to that seen with sirolimus-
      and paclitaxel-eluting stents in randomized controlled trials. At 3 years there
      was no occurrence of very late ST.

PMID- 21883475
TI  - Hydration status of patients with end-stage renal disease after kidney
      transplantation.
AB  - BACKGROUND: This study was carried out to estimate the modification of hydration
      status within the first three months of renal transplantation. SUBJECTS AND
      METHODS: Fifty patients who underwent a first kidney allograft were prospectively
      followed for three months after renal transplantation to assess hydration status
      by bioimpedance spectroscopy. RESULTS: Two hours before the transplant procedure,
      10/42 (23.8%) patients were overhydrated. Two days after surgery, 32/40 (80.0%)
      patients were overhydrated and at three months, 14/27 (51.9%) patients remained
      fluid-overloaded. Peritoneal dialysis (PD) patients had a lower hydration status
      (-0.60 L) than hemodialysis (HD) patients (0.70 L; p < 0.05) and better residual
      diuresis (41.7 vs. 8.3 mL/h for HD patients, p < 0.01). Compared with patients
      who had a delayed graft function (DGF) or a slow graft function (SGF), the
      immediate graft function (IGF) group had a better hydration status before
      transplantation (p = 0.031). At three months, 12/14 of the overhydrated patients
      had a creatinine clearance between 30 and 60 mL/min/1.73 m(2) . CONCLUSION:
      Patients receiving a first kidney transplant frequently have a hydration
      disorder. Transplantation is associated with increased hydration status, which
      seems to persist if DGF or SGF occurs.

PMID- 21883476
TI  - Genetic variations in multiple myeloma II: association with effect of treatment.
AB  - Association studies on genetic variation to treatment effect may serve as a
      predictive marker for effect of treatment and can also uncover biological
      pathways behind drug effect. Single-nucleotide polymorphisms (SNPs) have been
      studied in relation to high-dose treatment (HDT), thalidomide- and bortezomib
      based therapy, maintenance treatment with interferon-alpha and in relation to
      therapy-related adverse effects caused by treatment. Candidate genes for
      prediction of effect of HDT include DNA repair genes, CYP genes and genes
      involved in inflammation and apoptosis such as IL1B and RAI. In thalidomide- and
      bortezomid-based therapy, candidate genes include TNFA and genes involved in the
      nuclear factor kappa B pathway (NFKB2 and TRAF3), respectively. In maintenance
      treatment with interferon-alpha, a polymorphism in gene NFKB1 is a candidate gene
      for prediction for effect. Adverse effect includes infection, osteonecrosis of
      the jaw (ONJ), venous thrombotic events (VTE) and peripheral neuropathy (PN). A
      SNP in MBL2 and MPO gene was associated with septicemia and a SNP in the gene
      CYP2C8 was strongly associated with ONJ. Several SNPs in genes encoding DNA
      repair, apoptosis, inflammation and genes involved in function of the nervous
      system have been associated with VTE induced by thalidomide and with PN induced
      by bortezomib. SNP analysis is simple and can be performed, e.g., on blood and
      buccal cells. Further analysis of SNPs in clinical trials is needed, and
      collaboration between scientific groups will be an advantage because SNP analysis
      required large number of patients.

PMID- 21883477
TI  - Survival benefits from reduced-intensity conditioning in allogeneic stem cell
      transplantation for young lower-risk MDS patients without significant
      comorbidities.
AB  - OBJECTIVE: The aim of this study was to determine the optimum conditioning
      intensity for allogeneic stem cell transplantation (SCT) in young (age <=50),
      lower-risk (INT-1 by IPSS) Myelodysplastic syndrome (MDS) patients without
      significant comorbidities (hematopoietic cell transplantation-comorbidity index
      score <=3). METHODS: Transplant outcomes from 46 consecutive patients were
      retrospectively analyzed according to the conditioning intensity: reduced
      intensity conditioning (RIC; n = 14), intensified RIC by adding low-dose total
      body irradiation (iRIC; n = 15), and myeloablative conditioning (MAC; n = 17).
      RESULTS: After a median follow-up of 73.7 months, RIC had a better 4-yr overall
      survival (OS) (92.9%) compared with the iRIC (64.2%) or MAC (70.6%). Multivariate
      analysis showed that RIC was associated with improved OS compared with the MAC
      [relative risk (RR) of 0.08, P = 0.022] because of a lower transplant-related
      mortality (TRM) (RR, 0.08, P = 0.035). iRIC failed to show survival benefits over
      the MAC (RR of 0.77, P = 0.689) because of similarly high TRM (RR of 0.41, P =
      0.480). Cumulative incidence of acute and chronic graft-versus-host disease
      (GVHD) after RIC was higher, but GVHD-specific survival was significantly better
      (RIC 100% vs. iRIC 45.7% vs. MAC, P = 0.018). Relapse rate was not different
      among the three groups, but in the RIC group, azacitidine was available and
      useful for inducing remission in two patients. CONCLUSION: This study shows that
      RIC improved OS by directly lowering TRM and indirectly giving an additional
      chance for relapsed MDS in the era of hypomethylating treatment. RIC-SCT should
      be considered for relative healthy lower-risk MDS patients.

PMID- 21883478
TI  - Expression of CD66 in non-Hodgkin lymphomas and multiple myeloma.

PMID- 21883479
TI  - Reply to the letter to the editor by Guinn et al.

PMID- 21883480
TI  - Genetic variations in multiple myeloma I: effect on risk of multiple myeloma.
AB  - Few risk factors have been established for the plasma cell disorder multiple
      myeloma, but some of these like African American ethnicity and a family history
      of B-cell lymphoproliferative diseases suggest a genetic component for the
      disease. Genetic variation represents the genetic basis of variability in a
      population. The complex interplay between environment and genes for the
      development of cancer may therefore be influenced by genetic variations. A
      genetic variation may change the function of the gene, and if the genetic
      variation is associated with the risk of disease, that particular gene may be
      involved in the pathogenesis of disease. Genes of interest are genes involved in
      the normal development and function of the plasma cell and genes that protect us
      against exposures from the environment, for example, genes involved in the
      metabolism of xenobiotics, metabolism of folate and methionine, as well as genes
      involved in inflammation and DNA repair. Identification of genes with potential
      influence on cancer risk may help us to establish relevant laboratory studies on
      exposure and dose-response assessment and may help us to test the hypothesis in
      epidemiological studies. Knowledge of individual at high risk of cancer may offer
      promising insight for the prevention of cancer.

PMID- 21883481
TI  - Treatment of paroxysmal nocturnal hemoglobinuria in the era of eculizumab.
AB  - Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening and
      debilitating clonal blood disorder caused by an acquired mutation in the
      phosphatidylinositol glycan (PIG)-A gene. In pluripotent hematopoietic stem
      cells, this leads to a deficiency of glycosylphosphatidylinositol (GPI)-anchors
      and GPI-anchored proteins, including the complement regulators CD55 and CD59, on
      the surface of affected blood cells. PNH red blood cells are highly vulnerable to
      activation of complement and the formation of the membrane attack complex (MAC).
      The resulting chronic intravascular hemolysis is the underlying cause of PNH
      morbidities and mortality. Until recently, the treatment of PNH has been largely
      empirical and symptomatic with blood transfusions, anticoagulation, and
      supplementation with folic acid or iron. The only potentially curative treatment
      is allogeneic stem cell transplantation, but this has severe complications and
      high mortality and morbidity rates. A new targeted and disease-modifying
      treatment strategy is the inhibition of the terminal complement cascade with the
      humanized monoclonal anti-C5 antibody, eculizumab. This effectively inhibits MAC
      formation and intravascular hemolysis. Eculizumab has shown significant efficacy
      in controlled studies, with a marked decrease in anemia, fatigue, transfusion
      requirements, renal impairment, pulmonary hypertension, and risk of severe
      thromboembolic events, ultimately resulting in improving quality of life and
      survival.

PMID- 21883482
TI  - Low incidence and severity of graft-versus-host disease after outpatient
      allogeneic peripheral blood stem cell transplantation employing a reduced
      intensity conditioning.
AB  - BACKGROUND: The prevalence and features of graft-versus-host disease (GVHD) in
      patients receiving allografts using peripheral blood stem cells (PBSCs) after a
      reduced-intensity conditioning (RIC) regimen are not well known. Several features
      of GVHD in patients at two institutions using RIC were assessed. METHODS: We
      analysed the overall survival (OS) and prevalence of GVHD in patients who
      underwent outpatient allogeneic PBSC transplantation after RIC between October
      1998 and July 2008. RESULTS: We included 301 patients with a median age of 30 yrs
      (range, 1-71 yrs). In 37 cases, allogeneic peripheral blood stem cell
      transplantation was indicated for non-malignant disease, and in 264 for malignant
      disease. The median OS was 35 months. The estimated 3-yr OS was 48%. A total of
      154 patients developed GVHD: there were 64 acute, 50 chronic and 40 cases that
      progressed from acute to chronic. Of the 104 patients with acute GVHD (aGVHD),
      40% had grade I and 60% had grades II-IV. Of the 90 patients with chronic GVHD
      (cGVHD), 67% had limited and 33% had extensive forms. A total of 160 patients
      died, 40 as a result of GVHD (24 from aGVHD and 16 from cGVHD), 50 as a result of
      progressive disease and 70 from diverse causes. CONCLUSIONS: The incidence of
      GVHD was lower than in other series using conventional myeloablative preparative
      regimens. Most importantly, the severity of GVHD did not significantly affect the
      long-term survival.

PMID- 21883483
TI  - Cytoreductive treatment with clofarabine/ara-C combined with reduced-intensity
      conditioning and allogeneic stem cell transplantation in patients with high-risk,
      relapsed, or refractory acute myeloid leukemia and advanced myelodysplastic
      syndrome.
AB  - The combination of cytoreductive chemotherapy with reduced-intensity conditioning
      (RIC) is a highly effective antileukemic therapy. Purpose of this retrospective
      analysis was to evaluate the antileukemic efficacy and toxicity of clofarabine
      based chemotherapy followed by RIC and allogeneic stem cell transplantation (SCT)
      for high-risk, relapsed, or refractory acute myeloid leukemia (AML) or
      myelodysplastic syndromes (MDS). From May 2007 until October 2009, a total of 27
      patients underwent allogeneic SCT after treatment with clofarabine and ara-C for
      5d and RIC (4Gy TBI/cyclophosphamide/ATG). Prophylaxis of graft-versus-host
      disease (GvHD) consisted of cyclosporine and mycophenolate mofetil. Unmanipulated
      G-CSF mobilized PBSC (n=26) or bone marrow cells (n=1) were transplanted from
      unrelated (n=21) or matched related (n=6) donors. Non-hematological toxicities of
      this regimen mainly affected liver and skin and were all reversible. Seven
      patients relapsed within a median time of 5.7 months. The overall survival (OS)
      and relapse-free survival rates were 56% and 52% at 2 yr, respectively. In this
      cohort of patients, cytoreduction with clofarabine/ara-C (ClAraC) followed by RIC
      allogeneic SCT was well tolerated and showed good antileukemic efficacy even in
      patients with high-risk AML or MDS, with engraftment and GvHD-incidence
      comparable to other RIC regimens.

PMID- 21883484
TI  - Antifungal management and resource use in patients with acute myeloid leukaemia
      after chemotherapy--retrospective analysis of changes over 3 yr in a German
      hospital.
AB  - OBJECTIVES: To describe changes in costs of managing hospitalised patients with
      acute myeloid leukaemia (AML) after chemotherapy in Germany over 3 yr, with a
      special focus on prophylaxis and treatment patterns as well as resource use
      related to invasive fungal infections (IFI). METHODS: The study was conducted as
      a retrospective, single-centre chart review in patients with AML hospitalised for
      chemotherapy, neutropenia and infections after myelosuppressive chemotherapy from
      January 2004 to December 2006 in Germany. The following resource utilisation data
      were collected: inpatient stay, mechanical ventilation, parenteral feeding,
      diagnostics, systemic antifungal medication and cost-intensive concomitant
      medication. Direct medical costs were calculated from hospital provider
      perspective. RESULTS: A total of 471 episodes in 212 patients were included in
      the analysis. Occurrence of IFI decreased from 5.9% in 2004 to 1.9% in 2006. Mean
      (+/- standard deviation) hospital stay decreased from 28.7 +/- 17.9 d in 2004 to
      22.4 +/- 11.8 d in 2006. From 2004 to 2006, the use of a single antifungal drug
      increased from 30.4% to 46.9%, whereas the use of multiple antifungal drugs
      decreased from 24.4% to 13.1%. The use of liposomal amphotericin B declined
      between 2004 and 2006 (21.4% vs. 3.8%) and caspofungin between 2005 and 2006
      (19.3% vs. 8.1%). Total costs per episode declined from ?19051 +/- 19024 in 2004
      to ?13531 +/- 9260 in 2006; major reductions were observed in the use of
      antimycotics and blood products as well as length of hospital stay. CONCLUSION:
      Analysis of real-life data from one single centre in Germany demonstrated a
      change in antifungal management of patients with AML between 2004/2005 and 2006,
      accompanied by a decline in total costs.

PMID- 21883485
TI  - Fine-needle aspiration cytology: a reliable tool in the diagnosis of salivary
      gland lesions.
AB  - BACKGROUND: Fine-needle aspiration cytology (FNAC) is used as the main initial
      diagnostic investigation for lumps in the head and neck region. Major salivary
      glands and some minor salivary glands are easily accessible; therefore, they are
      optimal targets for FNAC. The aim of this study was to discuss the advantages and
      pitfalls of FNAC as compared to histopathology in the salivary gland lesions.
      MATERIAL AND METHODS: A total of 127 FNAC were carried out on salivary gland
      lesions from January 2006 to December 2010--a 5-year period. Histopathological
      follow-up data were obtained in 56 cases. The study was conducted to examine the
      sensitivity, specificity, and accuracy of FNAC for salivary gland swellings in
      comparison with histopathology. RESULTS: The male-to-female ratio was 2.4:1.
      Parotid gland was involved in 51.1%, submandibular gland in 37%, sublingual gland
      in 4.7%, and minor salivary glands in 7% of patients. There were 55.9% cases of
      non-neoplastic lesions and 44.1% cases of neoplastic lesions on biopsy.
      Sensitivity, specificity, positive predictive value, and negative predictive
      value of FNAC for malignant neoplastic lesions were 84.61%, 86.48%, 68.75%, and
      94.11%, respectively, whereas for benign neoplastic lesions, they were 84.61%,
      91.66%, 91.6%, and 85%, respectively. CONCLUSION: Fine-needle aspiration cytology
      is found to be a good sensitive and specific technique for the diagnosis of most
      of the salivary gland lesions. FNAC should be adopted as an initial investigation
      for all salivary gland swellings in conjunction with other investigations where
      appropriate.

PMID- 21883486
TI  - Evaluation of immunohistochemical expression of p53, p21, p27, cyclin D1, and
      Ki67 in oral and oropharyngeal squamous cell carcinoma.
AB  - BACKGROUND: The purpose of this study was to evaluate whether the
      immunohistochemical expression of p53, p21, p27, cyclin D1, and Ki67 can predict
      therapy response and survival in patients with oral and oropharyngeal squamous
      cell carcinoma treated with preoperative chemoradiation. METHODS: Biomarker
      expression was evaluated by immunohistochemistry in formalin-fixed, paraffin
      embedded pretreatment biopsies of 111 homogenously treated patients. We assessed
      the association between clinicopathological variables including response to
      neoadjuvant chemoradiotherapy as well as the survival of the patients and the
      expression of the biomarkers as both dichotomized (positive vs. negative) and
      continuous variables. RESULTS: Biomarker overexpression on the basis of pre
      selected cutoff points was seen in 66 of 111 (59%) cases for p53, in 77 (69%) for
      p21, in 48 (43%) for p27, in 81 (73%) for cyclin D1, and in 54 (49%) cases for
      Ki67, respectively. None of the examined biomarkers was able to predict response
      to neoadjuvant chemoradiotherapy or was associated with survival outcome. Post
      treatment pathologic TNM stage (P < 0.001), pathologic response (P < 0.001), and
      perineural invasion (P < 0.001) were the only factors having a significant effect
      on recurrence-free survival. Post-treatment pathologic N stage (P = 0.005), post
      treatment pathologic TNM stage (P < 0.001), pathologic response (P < 0.001), and
      perineural invasion (P = 0.001) had a significant impact on overall survival.
      CONCLUSIONS: Our results suggest that the biomarkers p53, p21, p27, cyclin D1,
      and Ki67 have no impact on treatment response and survival in patients with oral
      and oropharyngeal cancer treated with preoperative chemoradiation.

PMID- 21883487
TI  - Evaluation of oral mucosal diseases: inter- and intra-observer analyses.
AB  - BACKGROUND: Essential to the diagnosis and management of oral mucosal diseases
      are visual evaluation and monitoring of the oral cavity. Digital photography has
      recently become an important clinical tool. The aims of this study were to (i)
      evaluate inter- and intra-observer differences between oral medicine and other
      dental specialists when assessing changes in oral mucosal pathology and (ii)
      assess the influence of calibration labels incorporated into the clinical images
      on the reliability and consistency of evaluation. METHODS: Ten oral medicine
      specialists (OM) and 10 other dental specialists (DS) participated in the study.
      Pairs of images captured with an intraoral camera at two time points from 17
      cases of mucosal diseases were presented to the participants. Each pair of
      photographs was presented with a calibration label (showing length and white to
      black hues) and again without one. The participants were asked to respond to a
      questionnaire evaluating changes in size, color, location, and severity for each
      image pair. RESULTS: Oral medicine specialists had better absolute agreement and
      consistency than DS when evaluating the changes in the images; however, these
      parameters did not exceed 52% in either group. The incorporation of a calibration
      label in the images increased agreement and consistency of evaluations in both
      groups. CONCLUSIONS: Follow-up evaluations of oral mucosal lesions are performed
      better by oral medicine practitioners compared to other dental specialists. The
      incorporation of a calibration label in the clinical images seems to enhance
      evaluation.

PMID- 21883488
TI  - The prevalence of dysplasia and malignant lip lesions in transplant patients.
AB  - BACKGROUND: Solid organ transplant patients are at an increased risk of
      developing lip malignancies. The role of HLA mismatch as a risk factor for such
      changes has only been described in skin. METHODS: Lip lesions were evaluated in
      403 solid organ transplant patients (immunosuppressed for at least 3 months) and
      findings compared to age and sex matched, otherwise healthy patients who acted as
      controls. HLA typing was provided for the transplant patients. All patients
      provided details of smoking history, alcohol consumption, skin type, as assessed
      by ease of burning to sunlight, and exposure to sunlight or other forms of
      ultraviolet radiation. RESULTS: Lip lesions were identified in 36 transplant
      patients and 29 were biopsied. Fourteen of the biopsies confirmed dysplastic or
      malignant changes. For the control patients, one lesion was identified as
      dysplastic. The prevalence of dysplastic and malignant lip lesions was
      significantly higher (P = 0.006) in the transplant patients when compared to
      controls. Risk factors for dysplastic/malignant changes in the transplant group
      included age (P = 0.01), smoking (P = 0.033) and HLA-B mismatch (P = 0.001). Lip
      covering provided a significant reduction (P = 0.045) in the development of lip
      changes. CONCLUSION: All transplant patients should be regularly screened for lip
      malignancies and consulted on smoking and sunlight exposure. HLA-B mismatch does
      appear to make these patients more susceptible to dysplastic/malignant changes.

PMID- 21883489
TI  - Head and neck amyloidosis: clinicopathological features and immunohistochemical
      analysis of 14 cases.
AB  - BACKGROUND: Amyloidosis is associated with or caused by amyloid deposition. These
      fibrillar proteins may be deposited extracellularly causing tissue damage or
      impairment. OBJECTIVES: The aim of the study was to retrospectively review
      pathology archives in two oral diagnostic centers for cases fulfilling criteria
      of amyloidosis and to differentiate AA and AL types of amyloidosis. METHODS: The
      clinicopathological features, alkaline Congo red staining, with and without
      pretreatment with potassium permanganate, and immunohistochemical (IHC) staining
      with anti-AA, anti-kappa (kappa), and anti-lambda (lambda) light chain antibodies
      were carried out and analyzed. RESULTS: The search identified 14 cases. Ten
      patients were women and four were men, with a mean age of 58 years. Eleven
      patients had systemic involvement by amyloidosis (associated either with multiple
      myeloma or plasma cell dyscrasia/monoclonal gammopathies), while three presented
      the localized type, one of them associated with plasmacytoma. All cases showed
      positivity for kappa or lambda light chains (AL-amyloid) and presented resistance
      to the potassium permanganate pretreatment. CONCLUSIONS: Our results show that
      the head and neck region is preferentially affected by systemic AL-amyloidosis,
      usually associated with plasma cell dyscrasia. Interestingly, two cases affected
      by inflammatory rheumatic diseases presented AL-amyloid deposition. Moreover,
      even after pretreatment with potassium permanganate, which was helpful in
      highlighting the presence of AL-amyloid, in agreement with the IHC findings,
      clinical classifications should be carefully made in systemic amyloidosis.

PMID- 21883490
TI  - Characterizing ultrafine particles and other air pollutants at five schools in
      South Texas.
AB  - This study examined five schools with different ventilation systems in both urban
      and rural areas in South Texas. Total particle number concentration, ultrafine
      particle (UFP, diameter < 100 nm) size distribution, PM(2.5) , and CO(2) were
      measured simultaneously inside and outside of various school microenvironments.
      Human activities, ventilation settings, and occupancy were recorded. The study
      found a greater variation of indoor particle number concentration (0.6 * 10(3) 
      29.3 * 10(3) #/cm(3) ) than of outdoor (1.6 * 10(3) -16.0 * 10(3) #/cm(3) ). The
      most important factors affecting indoor UFP levels were related to various indoor
      sources. Gas fan heaters increased the indoor-to-outdoor ratio (I/O ratio) of
      total particle number concentrations to 30.0. Food-related activities, cleaning,
      and painting also contributed to the increased indoor particle number
      concentration with I/O ratios larger than 1.0. Without indoor sources, the I/O
      ratios for total particles varied from 0.12 to 0.66 for the five ventilation
      systems studied. The I/O ratio decreased when the outdoor total particle number
      concentration increased. Particles with diameters <60 nm were less likely to
      penetrate and stay airborne in indoor environments than larger particles and were
      measured with smaller I/O ratios. PRACTICAL IMPLICATIONS: From an exposure
      assessment perspective, schools are important and little-studied
      microenvironments where students congregate and spend a large proportion of their
      active time. This study provides information for indoor and outdoor ultrafine
      particle concentrations at different types of school microenvironments. These
      data may allow future epidemiological studies to better estimate exposure and
      assess ultrafine particles health effects among students.

PMID- 21883491
TI  - Importance of urinary flow studies after hypospadias repair: a systematic review.
AB  - A systematic review was performed of publications relating to the results of
      urinary flow studies after hypospadias repair dating back to 1978, when what
      appears to be the first publication on this topic was found. The literature
      search was performed using the key words "hypospadias" combined with "urinary
      flow", "urine flow", "uroflow", "uroflowmetry", and "long-term". We also reviewed
      the abstracts and full-length articles cited in the reference list of selected
      articles. Criteria for inclusion in the present systematic review included
      descriptions of patient selection, surgical technique, the severity of disease
      (proximal vs distal), and the method used to determine uroflow, as well as a
      definition of urethral obstruction. In all, 339 article titles were found. Of
      these, 25 abstracts appeared relevant and the full text of these articles were
      reviewed, with 22 of the papers included in this review. Sixteen reports had
      appeared in the literature since 2001, compared with six between 1978 and 2000,
      suggesting an increasing interest in this topic. On the basis of the results of
      the present systematic review, we recommend that asymptomatic children operated
      on for hypospadias in infancy should have one flow study after toilet training,
      with that study repeated if the results are abnormal. It appears that early
      abnormal flows improve spontaneously, so that children operated on after toilet
      training who are asymptomatic should undergo their first uroflow measurement 1
      year after surgery. Children with obstructed flow parameters or borderline flows
      should be followed until adulthood, until long-term follow up studies clarify the
      significance of abnormal flow parameters. Given the present findings, we
      anticipate that in the next two decades urologists will need to treat a number of
      men with strictures resulting from hypospadias repairs performed in childhood.

PMID- 21883492
TI  - Does testosterone deficiency exaggerate the clinical symptoms of Peyronie's
      disease?
AB  - Serum testosterone (T) influences wound healing and levels are decreased in the
      age group at risk of Peyronie's disease (PD). The aim of the present study was to
      evaluate the severity of penile deformity in men with PD in relation to T levels.
      One-hundred and six patients with PD and T deficiency (serum T <3.5 ng/mL; Group
      1) and those with normal T levels (Group 2) were compared according to the
      duration of PD, the size and location of the plaques, penile curvature, pain on
      erection, and the severity of erectile dysfunction. The mean degree of penile
      curvature in Group 1 was significantly greater than in Group 2 (32.0 +/- 15.9
      degrees  vs 21.8 +/- 15.4 degrees , respectively). The mean Group 1 score on the
      International Index of Erectile Function (IIEF)-5 was lower than the score for
      Group 2 (7.4 +/- 3.7 vs 10.8 +/- 4.8, respectively). The percentage of patients
      who complained of pain on erection did not differ between the two groups. Plaque
      size in Group 1 was larger than in Group 2 (3.0 +/- 1.2 vs 2.0 +/- 1.2 cm,
      respectively), whereas there was no significant difference in plaque location.
      Although there was a lower percentage of responders to medical treatment in Group
      1, there were no differences in surgical outcomes between the two groups. These
      findings suggest that the presence of T deficiency in patients with PD
      exaggerates the severity of PD by affecting penile deformity, plaque size, and
      erectile dysfunction. Further studies are needed to confirm this relationship.

PMID- 21883493
TI  - Editorial comment from Dr Ishidoya to increased expression of CYP17 and CYP11B1
      in subclinical Cushing's syndrome due to adrenal adenomas.

PMID- 21883494
TI  - Editorial comment from Dr Fang to increased expression of CYP17 and CYP11B1 in
      subclinical Cushing's syndrome due to adrenal adenomas.

PMID- 21883495
TI  - Serological screening for autoimmune polyendocrine syndromes in patients with
      vitiligo.

PMID- 21883496
TI  - Interaction of zearalenone and soybean isoflavone in diets on the growth
      performance, organ development and serum parameters in prepubertal gilts.
AB  - The aim of the present research was to determine the interactive effect of
      zearalenone (ZEA) and soybean isoflavone (ISO) on the growth performance,
      development of organs and serum parameters in prepubertal gilts. Ninety 75-day
      old female pigs (Duroc * Landrace * Yorkshire, 26.5 +/- 0.60 kg) were randomly
      allocated to nine diet treatments during the 21-day study. The experiment
      employed a 3 * 3 factorial design using a non-soybean meal diet with the addition
      of 0, 0.5 or 2.0 mg/kg ZEA and 0, 300 or 600 mg/kg ISO. The results indicated
      that simultaneous addition of ZEA and ISO had no significant influence on the
      growth performance in prepubertal gilts. Zearalenone with 2 mg/kg increased (p <
      0.05) the relative weight of the reproductive organs (including uterus and
      vagina) but had no obvious effects (p > 0.05) on the relative weight of the
      heart, liver, lung, kidney and spleen. Isoflavone at 600 mg/kg could offset the
      increased weight of the reproductive organs induced by ZEA. Simultaneous addition
      of ZEA and ISO to prepubertal gilts increased the level of alanine
      aminotransferase, aspartate aminotransferase and alkaline phosphatase in the
      serum (p < 0.05) at day 14 but their levels decreased (p < 0.05) over time.
      Zearalenone increased the level of malondialdehyde and decreased the
      concentrations of superoxide dismutase and glutathione peroxidase (p < 0.05) in
      the serum. The results suggested that ISO added to diets at 600 mg/kg could
      reduce the increase in the relative weight of reproductive organs and relieve the
      oxidative stress induced by ZEA added at 2 mg/kg during the growth phase in
      prepubertal gilts.

PMID- 21883497
TI  - Impact of dietary manganese concentration on status criteria to determine
      manganese requirement in piglets.
AB  - The Mn requirement for pigs is not well established. This study aimed to find
      criteria for assessing growing piglet supply status for Mn and to determine
      whether the current Mn recommendations meet the requirements for piglets. Thirty
      six weaned male castrated 27-day-old piglets (7.24 +/- 0.69 kg) were randomized
      into six groups of six piglets each and housed individually in stainless steel
      metabolic cages for 42 days. The piglets were fed a diet based on skimmed milk
      powder and corn starch with increasing Mn concentrations (0.24; 2; 4; 8; 16; or
      32 mg Mn/kg diet as-fed). In week 6, Mn0.24 led to reduced feed intake (p <
      0.05). Manganese concentrations in blood, liver, kidney, lung, heart, phalanx
      proximalis, pancreas and skeletal muscle were influenced by the dietary Mn supply
      (p < 0.05). The activity of the Mn-containing superoxide dismutase in the heart
      as well as relative arginase activity in the liver were lower in groups Mn0.24,
      Mn2 and Mn4 compared with the higher supplemented groups (p < 0.05). The relative
      arginase activity increased clearly with enhanced dietary Mn up to 16 mg/kg and
      correlated with Mn concentration in the liver. Manganese concentrations in the
      liver, kidney and phalanx proximalis seem to be suitable biomarkers for Mn
      status. A 4 mg/kg dietary Mn concentration recommended by NRC (1998, Nutrient
      Requirements of Swine. National Academy Press, Washington DC.) did not fulfil
      piglet requirements. Under the conditions investigated, 16 mg Mn/kg diet were
      necessary to reach a plateau in specific enzyme activity and Mn concentration in
      organs.

PMID- 21883498
TI  - Cats during gestation and lactation fed with canned food ad libitum: energy and
      protein intake, development of body weight and body composition.
AB  - The NRC recommendations for cats for energy and protein supply during gestation
      and lactation are based on limited data. This study aimed to answer the question:
      Can the energy requirement be met with canned food or is the volume restrictive?
      Therefore, balance trials were conducted in 10 queens before mating, during the
      4th and 7th week of gestation and during the 2nd and 6th week of lactation. The
      cats were fed with canned food ad libitum. Additionally, the body composition of
      the queens was measured by dual-energy X-ray absorptiometry (Dexa) before mating,
      after parturition and after weaning. Eight of 10 cats presented increased body
      fat content and lean body mass during gestation. The weight loss during lactation
      led to a loss of lean body mass, but only six cats lost body fat of widely
      differing amounts. It was evident that the queens' dry matter intake was
      consistent with that of queens fed ad libitum with dry food. The cats lost lean
      body mass during lactation and had negative protein balances in the 2nd week of
      lactation. This seems to be physiological in early lactation. Nevertheless, the
      protein recommendations for lactation seem to be too low.

PMID- 21883499
TI  - Effect of alternate day feeding strategy of sub-optimal protein level on haemato
      biochemical responses in Labeo rohita (Hamilton) juveniles.
AB  - A feeding trial was conducted for 60 days to delineate the effect of alternate
      day feeding strategy of sub-optimal protein level on haematological parameters,
      serum parameters and phagocyte respiratory burst activity (NBT) in Labeo rohita
      juveniles. One hundred and thirty-five fingerlings (1.87 +/- 0.01-2.26 +/- 0.05
      g) were distributed in triplicate groups of each treatment, and fish were fed at
      5% body weight daily. Three experimental isocaloric (401.32-410.28 kcal/100 g)
      diets of 30%, 25%, and 20% crude protein designated as diet A, diet B, and diet C
      respectively, were prepared, using locally available feed ingredients. Three
      different feeding schedules of normal protein diet continuously (diet A-30%),
      alternate feeding of 1-day diet A followed by 1-day diet B (1A/1B) and alternate
      feeding of 1-day diet A followed by 1-day diet C (1A/1C) were tested. The total
      erythrocyte count and haemoglobin content was significantly (p < 0.05) enhanced
      in the group T1 fed (1A/1B), and the lowest count was recorded in the group T2
      fed (1A/1C). Total leucocyte counts, total serum protein, and serum globulin were
      higher in the group T1 fed (1A/1B) and lower in the group T2 fed (1A/1C) as
      compare to control. The respiratory burst activity (NBT) of blood phagocytes and
      serum A-to-G ratio was recorded significantly difference in among the treatment
      groups. Based on the results of the present study, it is concluded that alternate
      feeding of 1-day diet A followed by 1-day diet B (1A/1B) is equally effective and
      promote the immunity in Labeo rohita juveniles.

PMID- 21883500
TI  - Fish oil supplementation improved liver phospholipids fatty acid composition and
      parameters of oxidative stress in male Wistar rats.
AB  - In the present study, we examined the effects of fish oil supplementation in 3
      months old male Wistar rats on changes in plasma and liver lipid metabolism and
      oxidative stress parameters. Twenty Wistar rats were randomly divided into two
      groups of ten animals: control group and intervention group, treated for 6 weeks
      with fish oil capsules containing 45 mg eicosapentanoic acid and 30 mg
      docosahexanoic acid. After intervention, biochemical parameters in plasma
      [triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein
      (HDL) and total cholesterol, urea, creatinine and uric acid], fatty acid (FAs)
      profile of liver phospholipids and parameters of oxidative stress in liver
      [activity of catalase, superoxide dismutase and paraoxonase (PON1), concentration
      of nitrites, lipid peroxidation (LPO), free thiol (SH) groups and lactate
      dehydrogenase (LDH) izoenzymes were determined. Treatment with fish oil improved
      FAs profile of liver phospholipids, increasing n-3 FAs and decreasing n-6/n-3
      ratio. Significant decrease in plasma TG and LDL concentration, and increase in
      the level of HDL and uric acid were found in intervention group at the end of the
      study. Catalase activity, LPO, and nitrites concentration in liver were
      significantly decreased, after the supplementation, together with elevated PON1
      activity. Applied treatment significantly improved plasma lipid profile, liver
      FAs composition and parameters of oxidative stress in male Wistar rats.

PMID- 21883501
TI  - Predicted metabolizable energy density and amino acid profile of the crop
      contents of free-living scarlet macaw chicks (Ara macao).
AB  - Hand rearing of neonates is a common practice for the propagation of psittacines.
      However, nutritional requirements for their growth and development are not well
      understood, and malnutrition is common. We analysed the amino acid (AA) profile
      of the crop contents of 19 free-living scarlet macaw (Ara macao) chicks, 19-59
      days old. Predicted metabolizable energy (PME) density was 16.9 MJ/kg DM and true
      protein (total AA protein) 8.3 g/MJ PME. Crude protein (CP) was 10.0 g/MJ PME,
      lower than the requirements of 0- to 12-week-old leghorn chicks but not different
      than the requirements of growing budgerigars (Melopsittacus undulatus) and
      lovebirds (Agapornis spp.). The mean concentrations of leucine, isoleucine,
      threonine, lysine (Lys) and methionine on a PME basis were below the minimum
      requirements of 0- to 12-week-old leghorn-type chicks. The calculated PME density
      of the samples did not vary with age. However, there was a significant negative
      correlation between the average age of the chicks and the Lys concentration. We
      conclude that the lower CP and AA densities compared with poultry could result
      from a combination of (i) differences in the essential AA composition of the body
      tissues, (ii) adaptations that allow the birds to grow on low-protein food
      sources and (iii) suboptimal nutrition of these free-ranging chicks.

PMID- 21883502
TI  - Colonisation in adult patients with nosocomial candidemia.
AB  - The aim of this prospective study was to investigate the association between
      Candida spp. isolated from blood culture and the colonisation of different
      anatomical sites of patients with candidemia, and to evaluate the colonisation
      dynamics and Pittet's index. Cultures were collected from the different
      anatomical sites of all the patients within 24 h of diagnosis of candidemia.
      Molecular similarities between identical species colonised with Candida species
      were evaluated via karyotyping. The colonisation index, as developed by Pittet et
      al. was calculated using screening culture results from patients. Among the 40
      patients screened for colonisation, 35 (87.5%) had colonisation of at least one
      anatomical site. Twenty-six (74.3%) of the 35 patients with colonisation in any
      of the three anatomical sites (respiratory, rectum and urinary sites) were shown
      to be colonised with the same species that caused candidemia. When the anatomical
      sites were compared with each other, no significant difference was observed at
      the species level in terms of colonisation index. The colonisation index (>= 0.5)
      positivity rate was 74% in patients with candidemia. The investigation of Candida
      colonisation of at least three anatomical (respiratory, rectum and urinary) sites
      could help in the selection of empirical antifungal therapy when nosocomial
      candidemia is suspected.

PMID- 21883503
TI  - Liver transplantation in patients with liver cirrhosis and active pneumonia: an
      observational study.
AB  - Patients with chronic liver disease are at high risk for severe infection because
      of increased bacterial translocation and immune suppression associated with liver
      dysfunction. Patients presenting with severe pneumonia and acute decompensation
      of cirrhosis are generally not considered for liver transplantation because it is
      unknown if these patients can recover from infection while under
      immunosuppression. We performed an observational study where patients with
      cirrhosis of the liver remained on the waiting list, although suffering from
      active pneumonia. Nine patients were included, but only six patients improved
      under goal-directed therapy and subsequently underwent liver transplantation. All
      six patients recovered quickly from infection; five patients recovered without
      sequelae and one patient died because of late complications. We propose that in
      patients with chronic liver disease and active pneumonia transplantation is a
      treatment option that should not hastily be abandoned.

PMID- 21883504
TI  - Single shot of alemtuzumab as induction therapy after kidney transplantation is
      sufficient.
AB  - In an earlier study, we were able to show that Tac monotherapy following 2 * 20
      mg alemtuzumab induction is at least as effective as Tac-based triple-drug
      immunosuppression in cadaveric renal transplantation. We were interested to learn
      whether 1 * 30 mg of alemtuzumab is as effective as 2 * 20 mg. Patients of the
      initial study group (group A) received 20 mg alemtuzumab on days 0 and 2, and tac
      monotherapy from day 2 on. This group acted as control group for the new arm
      (group C), where patients were given only 1 * 30 mg alemtuzumab on day 0 followed
      by Tac monotherapy from day 2 on with the same target levels as in the control
      group. Frequency of rejection at 6 months was 15% in the control group compared
      to 6% in the study group and 20% at 12 months in group A versus 6% in group C (P
      = 0.034). Time to rejection was 4.9 months in group A and 0.8 in group C. One
      year patient survival was 98.5% in both groups, graft survival 96.9% in group A,
      and 98.5% in group C. Safety profile was similar in both groups apart from more
      viral and bacterial infections in group C. Single shot alemtuzumab induction of
      30 mg is as effective as 2 * 20 mg in cadaveric renal transplantation.

PMID- 21883505
TI  - Accumulation of elderly ESRD patients with blood group O on the waiting list.

PMID- 21883506
TI  - Iron and acetaminophen a fatal combination?
AB  - Intentional iron overdose in adults is uncommon. Clinical consequences are
      variable and depend on the quantity of iron ingested and the delay to treatment.
      Severe iron overdose can lead to multi-organ failure and acute hepatic necrosis.
      Here, we report three cases of polypharmacy overdose including iron resulting in
      acute liver failure. Despite maximum supportive care including liver
      transplantation in two cases, all patients died. Iron poisoning may have an
      additive toxic effect in drug-induced acute liver failure and worsen outcome.

PMID- 21883507
TI  - Intravaginal progesterone devices in synchronization protocols for artificial
      insemination in beef heifers.
AB  - Two experiments were designed to investigate the administration of intravaginal
      progesterone in protocols for oestrus and ovulation synchronization in beef
      heifers. In Experiment 1, cyclic Black Angus heifers (n = 20) received an Ovsynch
      protocol and were randomly assigned to receive (CIDR-Ovsynch) or not (Ovsynch) a
      progesterone device between Days 0 and 7. Treatment with a controlled internal
      drug release (CIDR) device significantly increased the size of the dominant
      follicle prior to ovulation (12.8 +/- 0.4 CIDR-Ovsynch vs 11.4 +/- 0.4 Ovsynch)
      (p < 0.02). Plasma progesterone concentrations throughout the experiment were
      affected by the interaction between group and day effects (p < 0.004). In
      Experiment 2, cyclic Polled Hereford heifers (n = 382) were randomly assigned to
      one of the six treatment groups (3 * 2 factorial design) to receive a CIDR, a
      used bovine intravaginal device (DIB), or a medroxiprogesterone acetate (MAP)
      sponge and GnRH analogues (lecirelin or buserelin). All heifers received
      oestradiol benzoate plus one of the devices on Day 0 and PGF on Day 7 pm (device
      withdrawal). Heifers were detected in oestrus 36 h after PGF and inseminated 8-12
      h later, while the remainder received GnRH 48 h after PGF and were inseminated on
      Day 10 (60 h). The number of heifers detected in oestrus on Day 8 and conception
      rate to AI on Day 9 were higher (p < 0.01) in the used-DIB than in the CIDR or
      MAP groups, while the opposite occurred with the pregnancy rate to FTAI on Day 10
      (p < 0.01). There was no effect of progesterone source, GnRH analogue or their
      interaction on overall pregnancy rates (64.9%). Progesterone treatment of heifers
      during an Ovsynch protocol resulted in a larger pre-ovulatory follicle in beef
      heifers. Progesterone content of intravaginal devices in synchronization
      protocols is important for the timing of AI, as the use of low-progesterone
      devices can shorten the interval to oestrus.

PMID- 21883508
TI  - Progesterone production in mares and echographic evaluation of the corpora lutea
      formed after follicular aspiration.
AB  - Ultrasound-guided follicular aspiration was performed in 26 Criollo crossbred
      mares, followed by the evaluation of ultrasonographic images of the Corpus luteum
      (CL) that was formed after puncture of follicles of different diameters (Group 25
      29 mm; Group 30-35 mm and Group >35 mm). Serum progesterone (P(4) )
      concentrations were measured to determine CL function. The size of the CL was
      measured and the CL was classified based on the following echoscore: 1- anechoic
      tissue; 2- poorly defined luteal structure with low echogenicity; 3- echogenicity
      analogous to a luteal structure. The proportion of aspirated follicles that
      formed a functional CL (based on P(4) concentration) 8 days after aspiration was
      57.1% (4/7; CL size 25-29 mm), 75.0% (6/8; CL size 30-35 mm) and 72.7% (8/11; CL
      size >35 mm), respectively (p > 0.05). The echographic scores of aspirated
      follicles (indicating the presence or absence of a CL) were consistent with serum
      P(4) concentrations (p < 0.0001). Of 26 aspirations, 18 resulted in luteal
      function confirmed by increased progesterone concentrations ([P(4) ] > 1.0
      ng/ml); 17 of these mares (94.4%) had an echoscore (2-3) compatible with
      luteinization (p = 0.0372). Eight days after aspiration, serum [P(4) ] > 2.0
      ng/ml was associated with high (p = 0.0056) CL echoscore (3) in 15 of 17 mares
      (88.2%). The echoscore used in this study was valuable as a screening test to
      detect the presence of a functional CL after aspiration. An echoscore of 3 served
      as a practical and efficient method to confirm luteinization.

PMID- 21883509
TI  - Effect of different egg yolk-based extenders on the quality of ovine cauda
      epididymal spermatozoa during storage at 4 degrees C.
AB  - Cauda epididymal spermatozoa were obtained from testicles collected from
      abattoir(s). The pooled sperm samples were divided into four aliquots. Each
      aliquot was washed separately with the buffer of respective extender and finally
      extended with the four extenders viz. egg yolk-citrate (EYC), egg yolk-citrate
      fructose (EYCF), Tris-citric acid-egg yolk-fructose (TCEYF) and egg yolk
      Mcillvaine glucose (EYMG) and preserved at 4 degrees C. The per cent sperm
      motility for EYC, EYCF, TCEYF and EYMG at 0 h was 50.83%, 56.67%, 75.00% and
      31.67%, respectively, and at 72 h was 24.17% (EYC), 30.83% (EYCF), 51.67% (TCEYF)
      and 7.50% (EYMG). The corresponding figures for live sperm count at 0 h was
      83.17%, 86.33%, 90.42% and 81.75% and at 72 h was 64.75%, 73.92%, 76.00% and
      57.67%. The corresponding figures for mean per cent intact acrosome at 0 h was
      95.33%, 95.50%, 90.92% and 97.25% and at 72 h was 86.17%, 83.92%, 77.58% and
      86.33%. The sperm motility was significantly (p < 0.05) higher for TCEYF at
      different h of preservation from 0 h through 72 h. The sperm motility, live sperm
      count and per cent intact acrosome declined significantly (p < 0.05) with the
      advancement of storage time in all the four extenders. Our study concluded that
      TCEYF was best out of the extenders studied for preservation of cauda epididymal
      spermatozoa after double centrifugation and extension at 4 degrees C up to 72 h
      of preservation. However, EYCF also has better potential for the preservation of
      cauda epididymal spermatozoa as viability was in close proximity and acrosomal
      integrity was higher compared with TCEYF extender.

PMID- 21883510
TI  - Luteal function and follicular growth following follicular aspiration during the
      peri-luteolysis period in Bos indicus and crossbred cattle.
AB  - Follicular estradiol triggers luteolysis in cattle. Therefore, the control of
      follicle growth and steroidogenesis is expected to modulate luteal function and
      might be used as an anti-luteolytic strategy to improve embryo survival.
      Objectives were to evaluate follicular dynamics, plasma concentrations of
      estradiol and luteal lifespan in Bos indicus and crossbred cows subjected to
      sequential follicular aspirations. From D13 to D25 of a synchronized cycle
      (ovulation = D1), Nelore or crossbred, non-pregnant and non-lactating cows were
      submitted to daily ultrasound-guided aspiration of follicles >6 mm (n = 10) or to
      sham aspirations (n = 8). Diameter of the largest follicle on the day of
      luteolysis (7.4 +/- 1.0 vs 9.7 +/- 1.0 mm; mean +/- SEM), number of days in which
      follicles >6 mm were present (2.3 +/- 0.4 vs 4.6 +/- 0.5 days) and daily mean
      diameter of the largest follicle between D15 and D19 (6.4 +/- 0.2 vs 8.5 +/- 0.3
      mm) were smaller (p < 0.01) in the aspirated group compared with the control
      group, respectively. Aspiration tended to reduce (p < 0.10) plasma estradiol
      concentrations between D18 and D20 (2.95 +/- 0.54 vs 4.30 +/- 0.55 pg/ml). The
      luteal lifespan was similar (p > 0.10) between the groups (19.6 +/- 0.4 days),
      whereas the oestrous cycle was longer (p < 0.01) in the aspirated group (31.4 +/-
      1.2 vs 21.2 +/- 1.3 days). Hyperechogenic structures were present at the sites of
      aspiration and were associated with increase in concentration of progesterone
      between luteolysis and oestrus. It is concluded that follicular aspiration
      extended the oestrous cycle and decreased the average follicular diameter on the
      peri-luteolysis period but failed to delay luteolysis.

PMID- 21883511
TI  - DGAT1, GH, GHR, PRL and PRLR polymorphism in water buffalo (Bubalus bubalis).
AB  - The polymorphism of several genes has been shown to affect the milk composition
      traits in dairy cattle, including DGAT1-exon8 K232A, GH-intron3 MspI, GH-exon5
      AluI, GHR-exon8 F279Y, PRL-exon3 RsaI and PRLR-exon3 S18N. However, the
      polymorphism and effects of these genes on the milk traits of water buffalo are
      still unclear. In this study, four DNA pooling samples from Murrah, Nili-ravi,
      Murrah-Nili-Swamp crossbreed and Chinese swamp buffalo were constructed,
      respectively, and polymorphism of these sites was investigated using PCR-Single
      strand conformation polymorphism and sequencing. Twenty-eight inter-specific
      single-nucleotide polymorphism (SNPs) were found in these six assayed gene
      fragments between buffalo and dairy cattle, including nine intra-specific SNPs
      among buffalo groups. All buffalo fixed a K allele genotype in DGAT1-exon8,
      MspI(+)  restriction site(c nucleotide) and AluI(+)  site(c nucleotide) at
      intron3 and exon5 of GH gene, F allele genotype of F279Y mutation in GHR gene,
      RsaI(-)  restriction site at PRL-exon3/exon4 and N allele genotype of S18N
      mutation at PRLR-exon3. It provides an indirect evidence that water buffalo have
      fixed alleles with genotypes reported in dairy cattle, which is thought to be
      responsible for high milk fat, high protein content and low milk yield. Moreover,
      three new intra-specific SNPs were found including 275th bp (c/t) in DGAT1 of
      Murrah buffalo, 109th bp (t/a) in PRL-exon3/exon4 and 43rd bp (c/t) in PRLR-exon3
      of Chinese swamp buffalo. Information provided in this study will be useful in
      further studies to improve buffalo breeding for better lactation performances.

PMID- 21883512
TI  - Alternative treatment of ovarian cysts with Tribulus terrestris extract: a rat
      model.
AB  - Tribulus terrestris has long been used in traditional medicine to treat impotency
      and improve sexual functions in man. The aim of this study was to evaluate the
      efficiency of T. terrestris extract in the treatment of polycystic ovary (PCO) in
      Wistar rat. Estradiol valerate was injected to 15 mature Wistar rats to induce
      PCO. Rats were randomly divided into three groups (control, low-dose and high
      dose groups) of five each and received 0, 5 and 10 mg of T. terrestris extract,
      respectively.Treatments began on days 50 and 61 after estradiol injection; at the
      same time, vaginal smear was prepared. The ovaries were removed on day 62, and
      histological sections were prepared accordingly. The number and diameter of
      corpora lutea, thickness of the theca interna layer and the number of all
      follicles were evaluated in both ovaries. In comparison with the control group,
      the number of corpora lutea and primary and secondary follicles significantly
      increased following T. terrestris treatment; however, the number of ovarian cysts
      significantly decreased. It can be concluded that T. terrestris have a
      luteinizing effect on ovarian cysts, which may relate to its gonadotropin-like
      activity; also, a high dose of the extract can efficiently remove ovarian cysts
      and resume ovarian activity.

PMID- 21883513
TI  - Follicle formation in the canine ovary after autografting to a peripheral site.
AB  - This study reports about follicular development on the surface of canine ovarian
      tissue after autografting under the fascia of the thoracolumbar muscle and about
      meiotic resumption of follicle-derived oocyte after maturation culture. After
      ovarian excision from a bitch, each ovary of the pairs was cut approximately into
      half. The hemi-ovaries were transplanted into the bitch of origin at three
      different body sites (under the fascia of the quadriceps femoris muscle and the
      thoracolumbar muscle, and in the deltoid muscle in the scapular region). All
      grafted ovaries were recovered from the bitch at 35 days post-transplantation. A
      visible antral follicle was observed on the surface of the ovary grafted under
      the thoracolumbar fascia. Histological examination revealed viable follicles at
      different stages of development irrespective of graft site. Most granulosa cells
      in the follicles at different stages of development expressed proliferating cell
      nuclear antigen (PCNA). A total of three oocytes were collected from an ovary
      grafted under the fascia of the thoracolumbar muscle, wherein an oocyte reached
      metaphase I after maturation culture. This is the first report to demonstrate
      follicular development and meiotic resumption of oocytes recovered from
      autografted canine ovarian tissues.

PMID- 21883514
TI  - The effect of LIF in the absence or presence of FSH on the in vitro development
      of isolated caprine preantral follicles.
AB  - We investigated the effect of the leukaemia inhibitory factor (LIF) alone or in
      association with FSH on the in vitro culture (IVC) of caprine preantral
      follicles. Preantral follicles >200 MUm in size were isolated and cultured for 18
      days in basic medium either alone (control) or supplemented with LIF (10 or 50
      ng/ml) in the absence or presence of FSH. Every 6 days, follicular survival,
      growth and antrum formation were evaluated. At the end of the culture period, the
      oocytes underwent in vitro maturation (IVM), and their viability and chromatin
      configuration were assessed. Follicles of the control group and those cultured in
      10 ng/ml LIF maintained the structural integrity (particularly the preservation
      of the basement membrane) when compared to the oocytes cultured in 50 ng/ml LIF,
      regardless the presence of FSH. In the absence of FSH, the percentage of antrum
      formation after 18 days of culture in the 50 ng/ml LIF group was significantly
      lower than in either the control group or the 10 ng/ml LIF group. However, this
      effect was not observed in the presence of FSH. The rate of resumption of meiosis
      was significantly higher in the 50 ng/ml LIF group in the absence of FSH in
      comparison with the control and 10 ng/ml LIF groups. Metaphase II was observed
      only when follicles were cultured in a combination of FSH and 50 ng/ml LIF. In
      conclusion, LIF alone does not interfere with antral formation and oocyte growth,
      but at concentration of 50 ng/ml and combined with FSH, it promotes oocyte
      maturation.

PMID- 21883515
TI  - Reproductive technologies relevant to the genome resource bank in Carnivora.
AB  - Carnivora is one of the most species-rich order of Mammalia. Some species, e.g.
      domestic cats, dogs and ferrets, are among the most popular pets; others, such as
      minks and farmed foxes, have economic value for the fur breeding industry. Still
      others, such as tigers, bears and other top predators, have great impact on the
      health of natural ecosystems. Most if not all Carnivora species have great
      cultural and aesthetic importance for man. There are enormous differences between
      mammalian species in reproductive physiology, and it is not surprising that
      reproductive technologies can be used with high efficiency with some animal
      groups, e.g. most farm animals and laboratory rodents, but are very laborious
      when used with Carnivora species, which often possess unique reproductive traits.
      The efficiency of assisted reproductive technology (ART) applied to semi
      domestic, non-domestic and especially to endangered species of Carnivora remains
      extremely low in most cases, and often the first positive result reported is the
      only instance when ART has been successful with that species. Although there are
      approximately 270 species in the Carnivora order, to the best of our knowledge,
      successful published attempts to apply ART have been reported for only four
      families: Mustelidae, Felidae, Canidae and Ursidae. The main achievements in ART,
      embryo technology in particular, for these families of Carnivora, together with
      challenges and problems, are reviewed in the relevant sections.

PMID- 21883516
TI  - Effects of seasons on some semen parameters and bacterial contamination of Awassi
      ram semen.
AB  - The objectives of the present study were to determine the effects of season on
      some semen parameters and bacterial contamination of Awassi ram semen. Semen
      samples from six mature Awassi rams were used in this study. Semen collection was
      performed with artificial vagina every week, from September 2009 to October 2010.
      Volume, sperm concentration, mass motility, individual motility, percentage live
      sperm and sperm abnormalities were evaluated. Moreover, determination of viable
      bacterial count of the rams was also recorded weekly. Higher (p < 0.05) semen
      volume in the hot summer and spring months was observed of August (1.55 +/- 0.08
      ml) and March (1.27 +/- 0.15 ml). Sperm concentration was highest (p < 0.05) in
      the breeding season (late summer to early autumn) of September (4.21 +/- 0.86 *
      10(9) sperm/ml). Sperm individual motility and percent of live sperm observed in
      August (summer) and May (end of spring) when the environmental temperature
      started to increase were recorded highest values and differed significantly (p <
      0.05) from December and January (winter). The highest value of the mean sperm
      acrosomal defects (13.33 +/- 0.63%) was recorded in December. The highest value
      of the mean viable bacterial count (138.3 +/- 21.6) was recorded in July
      (summer). A significant decrease (p < 0.01) in the mean viable bacterial count
      was observed from the middle of winter towards the end of spring. The lowest
      bacterial count was noted in January (60.5 +/- 2.98). It could be concluded from
      the results of the present study that there is an effect of season on ram semen
      quality, and summer high temperature in northern Iraq has no effect on Awassi ram
      semen. There is a significant effect of season on bacterial count on Awassi ram
      semen.

PMID- 21883517
TI  - Ultrasonography and progesterone concentration at a single time point for the
      detection of puberty in dairy heifers.
AB  - Data were available from 1657 heifers across 48 dairy farms which were visited
      once, on average 9 days (+/- 5.2) prior to the mating start date (23 April, +/-
      12.6). Blood samples were collected via coccygeal venepuncture for progesterone
      (P4) analysis, and animals were scanned for the presence or absence of corpora
      lutea (CL), to determine the luteal status. A comparison of luteal status between
      ultrasound (CL identified) and P4 (>= 1 ng/ml), based on a single measurement
      point, showed poor agreement (K = 0.32). The majority of animals were classified
      as luteal (76%) using both ultrasonography and P4. There was excellent agreement
      between luteal status detected by ultrasonography alone and luteal status
      assigned by a combination of ultrasonography and P4 (K = 0.93). The agreement
      between luteal status assigned by P4 and luteal status assigned by the
      combination of ultrasonography and P4 was poor (K = 0.37). These results indicate
      that at a single examination, ultrasonography is the preferred modality to
      determine the luteal status of maiden heifers.

PMID- 21883518
TI  - Influence of the length of progestagen treatment and the time of oestradiol
      benzoate application on the ovulatory follicle size and ovulation time in
      anoestrous and cyclic beef cows.
AB  - Previous research from our laboratory in beef cattle suggests that the pre
      ovulatory follicle size, maturity and subsequent susceptibility to gonadotropin
      are influenced by the length of progestagen treatment in artificial insemination
      programme in beef cows. To test this hypothesis, two experiments were conducted.
      In experiment 1, 35 anoestrous beef cows received an intravaginal sponge
      containing 200 mg of medroxyprogesterone acetate. The treatment lasted for 7 (n =
      12), 8 (n = 11) or 9 (n = 12) days. Half of the animals in each group were
      injected with 0.7 mg of oestradiol benzoate (EB) at device removal (0 h) and the
      other half 24 h later. In experiment 2, 38 cycling beef cows were treated with
      the same protocols as in experiment 1. Ultrasound examinations were performed to
      determine the follicular diameter at device removal (dominant follicle), interval
      to ovulation and ovulatory follicle diameter. The dominant follicle of anoestrous
      cows with progestagen for 7 days (8.4 +/- 1.6 mm) resulted smaller (p < 0.05)
      than the cows treated for 8 (10.5 +/- 1.6 mm) and 9 days (10.6 +/- 1.2 mm).
      However, regardless of the length of the treatments, ovulation time after device
      removal was longer (p < 0.05) when EB was injected 24 h after withdrawal than at
      0 h in anoestrous cows (EB0 = 52.7 +/- 4.0 h; EB24 = 70.8 +/- 6.2 h) and in
      cyclic cows (EB0 = 50.0 +/- 21.0 h; EB24 = 73.0 +/- 20.0 h). In anoestrous cows,
      the treatment with progestagen for 9 days and EB at 24 h increased the diameter
      of the ovarian follicle (p = 0.033) but did not affect the diameter of the
      ovulatory follicle in cyclic cows. In conclusion, increasing the length of
      progestagen treatment for 8 or 9 days compared to 7 days increased the diameter
      of the dominant follicle, in anoestrous and cyclic beef cows. Oestradiol benzoate
      administered at device removal resulted in a shorter interval from device removal
      to ovulation compared with EB injection 24 h after the end of a progestagen
      treatment.

PMID- 21883520
TI  - RepC protein of the octopine-type Ti plasmid binds to the probable origin of
      replication within repC and functions only in cis.
AB  - Vegetative replication and partitioning of many plasmids and some chromosomes of
      alphaproteobacteria are directed by their repABC operons. RepA and RepB proteins
      direct the partitioning of replicons to daughter cells, while RepC proteins are
      replication initiators, although they do not resemble any characterized
      replication initiation protein. Here we show that the replication origin of an
      Agrobacterium tumefaciens Ti plasmid resides fully within its repC gene. Purified
      RepC bound to a site within repC with moderate affinity, high specificity and
      with twofold cooperativity. The binding site was localized to an AT-rich region
      that contains a large number of GANTC sites, which have been implicated in
      replication regulation in related organisms. A fragment of RepC containing
      residues 26-158 was sufficient to bind DNA, although with limited sequence
      specificity. This portion of RepC is predicted to have structural homology to
      members of the MarR family of transcription factors. Overexpression of RepC in A.
      tumefaciens caused large increases in copy number in cis but did not change the
      copy number of plasmids containing the same oriV sequence in trans, confirming
      other observations that RepC functions only in cis.

PMID- 21883521
TI  - Strict regulation of morphological differentiation and secondary metabolism by a
      positive feedback loop between two global regulators AdpA and BldA in
      Streptomyces griseus.
AB  - AdpA is a global transcriptional regulator that is induced by the microbial
      hormone A-factor and activates many genes required for morphological
      differentiation and secondary metabolism in Streptomyces griseus. We confirmed
      that the regulatory tRNA gene bldA was required for translation of TTA-containing
      adpA. We also demonstrated that AdpA bound two sites upstream of the bldA
      promoter and activated transcription of bldA. Thus, we revealed a unique positive
      feedback loop between AdpA and BldA in S. griseus. Forced expression of bldA in
      an A-factor-deficient mutant resulted in the partial restoration of aerial
      mycelium formation and streptomycin production, suggesting that the positive
      feedback loop could prevent premature transcriptional activation of the AdpA
      target genes in the wild-type strain. We revealed that the morphological defect
      of the bldA mutant could be attributed mainly to the TTA codons of only two
      genes: adpA and amfR. amfR encodes a transcriptional activator essential for
      aerial mycelium formation and is a member of the AdpA regulon. Thus, amfR is
      regulated by a feedforward mechanism involving AdpA and BldA. We concluded that
      the central regulatory unit composed of AdpA and BldA plays important roles in
      the initiation of morphological differentiation and secondary metabolism
      triggered by A-factor.

PMID- 21883519
TI  - The MAP kinase MpkA controls cell wall integrity, oxidative stress response,
      gliotoxin production and iron adaptation in Aspergillus fumigatus.
AB  - The saprophytic fungus Aspergillus fumigatus is the most important air-borne
      fungal pathogen. The cell wall of A. fumigatus has been studied intensively as a
      potential target for development of effective antifungal agents. A major role in
      maintaining cell wall integrity is played by the mitogen-activated protein kinase
      (MAPK) MpkA. To gain a comprehensive insight into this central signal
      transduction pathway, we performed a transcriptome analysis of the DeltampkA
      mutant under standard and cell wall stress conditions. Besides genes involved in
      cell wall remodelling, protection against ROS and secondary metabolism such as
      gliotoxin, pyomelanin and pseurotin A, also genes involved in siderophore
      biosynthesis were regulated by MpkA. Consistently, northern and western blot
      analyses indicated that iron starvation triggers phosphorylation and thus
      activation of MpkA. Furthermore, localization studies indicated that MpkA
      accumulates in the nucleus under iron depletion. Hence, we report the first
      connection between a MAPK pathway and siderophore biosynthesis. The measurement
      of amino acid pools and of the pools of polyamines indicated that arginine was
      continuously converted into ornithine to fuel the siderophore pool in the
      DeltampkA mutant strain. Based on our data, we propose that MpkA fine-tunes the
      balance between stress response and energy consuming cellular processes.

PMID- 21883522
TI  - Termination of Vibrio cholerae virulence gene expression is mediated by
      proteolysis of the major virulence activator, ToxT.
AB  - Vibrio cholerae is the causative agent of cholera, a severe diarrhoeal illness.
      V. cholerae produces two major virulence factors: the cholera toxin, which
      directly causes diarrhoea, and the toxin-coregulated pilus, which is required for
      intestinal colonization. Production of these virulence factors is dependent on
      the major virulence regulator, ToxT. Under virulence-inducing growth conditions,
      transcription factors ToxR and TcpP initially activate transcription of toxT.
      However, once ToxT has been expressed, it produces more of itself independent of
      ToxR and TcpP by activating transcription of the long tcpA operon, within which
      toxT is located. It is known that V. cholerae terminates virulence gene
      expression prior to escape from the host, but it is unknown how this ToxT
      positive feedback loop is broken, an essential step in terminating virulence gene
      expression. To better understand how ToxT protein activity is regulated, we
      monitored ToxT accumulation and activity under virulence-inducing and -repressing
      growth conditions. Our results suggest that ToxT protein undergoes proteolytic
      degradation to terminate virulence gene expression. This directed degradation of
      ToxT supports a model for terminating V. cholerae virulence gene expression late
      in infection, with both ToxT and TcpP undergoing proteolysis prior to escape from
      the host.

PMID- 21883523
TI  - Chlamydia trachomatis Slc1 is a type III secretion chaperone that enhances the
      translocation of its invasion effector substrate TARP.
AB  - Bacterial type III secretion system (T3SS) chaperones pilot substrates to the
      export apparatus in a secretion-competent state, and are consequently central to
      the translocation of effectors into target cells. Chlamydia trachomatis is a
      genetically intractable obligate intracellular pathogen that utilizes T3SS
      effectors to trigger its entry into mammalian cells. The only well-characterized
      T3SS effector is TARP (translocated actin recruitment protein), but its chaperone
      is unknown. Here we exploited a known structural signature to screen for putative
      type III secretion chaperones encoded within the C. trachomatis genome. Using
      bacterial two-hybrid, co-precipitation, cross-linking and size exclusion
      chromatography we show that Slc1 (SycE-like chaperone 1; CT043) specifically
      interacts with a 200-amino-acid residue N-terminal region of TARP (TARP1-200).
      Slc1 formed homodimers in vitro, as shown in cross-linking and gel filtration
      experiments. Biochemical analysis of an isolated Slc1-TARP1-200 complex was
      consistent with a characteristic 2:1 chaperone-effector stoichiometry.
      Furthermore, Slc1 was co-immunoprecipitated with TARP from C. trachomatis
      elementary bodies. Also, coexpression of Slc1 specifically enhanced host cell
      translocation of TARP by a heterologous Yersinia enterocolitica T3SS. Taken
      together, we propose Slc1 as a chaperone of the C. trachomatis T3SS effector
      TARP.

PMID- 21883524
TI  - The evolution of a superbug: how Staphylococcus aureus overcomes its unique
      susceptibility to polyamines.
AB  - Polyamines are ubiquitous compounds thought to be synthesized by and required for
      all life. The manuscript published in this issue by Joshi and colleagues upsets
      this dogma by identifying several bacterial species that do not make polyamines,
      and in some cases do not require polyamines for growth. One such species is the
      significant human pathogen Staphylococcus aureus, which is shown to be uniquely
      sensitive to polyamines. By unravelling the mechanisms of staphylococcal
      polyamine toxicity and tolerance, Joshi et al. (2011) provide insights into how
      the most virulent strains of S. aureus have evolved to be more fit during
      infection.

PMID- 21883525
TI  - A novel role of 'pseudo'gamma-butyrolactone receptors in controlling gamma
      butyrolactone biosynthesis in Streptomyces.
AB  - In streptomycetes, a quorum-sensing mechanism mediated by gamma-butyrolactones
      (GBLs) and their cognate receptors was known to trigger secondary metabolism and
      morphological differentiation. However, many aspects on the control of GBL signal
      production are not understood. In this work, we report that ScbR2, the pseudo GBL
      receptor in Streptomyces coelicolor, negatively controls the biosynthesis of
      gamma-butyrolactone (SCB1) by directly repressing the transcription of scbA,
      which encodes the key enzyme for SCB1 biosynthesis. Similarly, the pseudo GBL
      receptor JadR2 in Streptomyces venezuelae was shown to repress the expression of
      jadW1, which also encodes the putative GBL synthase. These regulatory
      relationships were verified in Escherichia coli using lux-based reporter
      constructs. Additionally, the temporal expression profiles of scbA, scbR2 and
      scbR (receptor gene for SCB1) were examined in Streptomyces coelicolor, which
      showed the sequential expression of ScbR/R2 regulators in the control of SCB1
      production. Overall, our results clearly demonstrated that pseudo GBL receptors
      play a novel role in controlling GBL biosynthesis in streptomycetes. As ScbR/R2
      homologues and their binding sites upstream of GBL synthase genes are commonly
      found in Streptomyces species, and ScbR2 homologues cross-recognize each other's
      target promoters, the ScbA/R/R2 quorum-sensing regulatory system appears to
      represent an evolutionarily conserved signal control mechanism.

PMID- 21883526
TI  - Atypical DNA recognition mechanism used by the EspR virulence regulator of
      Mycobacterium tuberculosis.
AB  - The human pathogen Mycobacterium tuberculosis requires the ESX-1 secretion system
      for full virulence. EspR plays a key role in ESX-1 regulation via direct binding
      and transcriptional activation of the espACD operon. Here, we describe the
      crystal structures of EspR, a C-terminally truncated form, EspRDelta10, as well
      as an EspR-DNA complex. EspR forms a dimer with each monomer containing an N
      terminal helix-turn-helix DNA binding motif and an atypical C-terminal
      dimerization domain. Structural studies combined with footprinting experiments,
      atomic force microscopy and molecular dynamic simulations allow us to propose a
      model in which a dimer of EspR dimers is the minimal functional unit with two
      subunits binding two consecutive major grooves. The other two DNA binding domains
      are thus free to form higher-order oligomers and to bridge distant DNA sites in a
      cooperative way. These features are reminiscent of nucleoid-associated proteins
      and suggest a more general regulatory role for EspR than was previously
      suspected.

PMID- 21883527
TI  - The CRP/FNR family protein Bcam1349 is a c-di-GMP effector that regulates biofilm
      formation in the respiratory pathogen Burkholderia cenocepacia.
AB  - Burkholderia cenocepacia is an opportunistic respiratory pathogen that can cause
      severe infections in immune-compromised individuals and is associated with poor
      prognosis for patients suffering from cystic fibrosis. The second messenger
      cyclic diguanosine monophosphate (c-di-GMP) has been shown to control a wide
      range of functions in bacteria, but little is known about these regulatory
      mechanisms in B. cenocepacia. Here we investigated the role that c-di-GMP plays
      in the regulation of biofilm formation and virulence in B. cenocepacia. Elevated
      intracellular levels of c-di-GMP promoted wrinkly colony, pellicle and biofilm
      formation in B. cenocepacia. A screen for transposon mutants unable to respond to
      elevated levels of c-di-GMP led to the identification of the mutant bcam1349 that
      did not display increased biofilm and pellicle formation with excessive c-di-GMP
      levels, and displayed a biofilm defect with physiological c-di-GMP levels. The
      bcam1349 gene is predicted to encode a transcriptional regulator of the CRP/FNR
      superfamily. Analyses of purified Bcam1349 protein and truncations demonstrated
      that it binds c-di-GMP in vitro. The Bcam1349 protein was shown to regulate the
      production of a number of components, including cellulose and fimbriae. It was
      demonstrated that the Bcam1349 protein binds to the promoter region of the
      cellulose synthase genes, and that this binding is enhanced by the presence of c
      di-GMP. The bcam1349 mutant showed reduced virulence in a Galleria mellonella wax
      moth larvae infection model. Taken together, these findings suggest that the
      Bcam1349 protein is a transcriptional regulator that binds c-di-GMP and regulates
      biofilm formation and virulence in B. cenocepacia in response to the level of c
      di-GMP.

PMID- 21883529
TI  - Novel roles of LeuO in transcription regulation of E. coli genome: antagonistic
      interplay with the universal silencer H-NS.
AB  - LeuO, the regulator of leucine biosynthesis operon of Escherichia coli, is
      involved in the regulation of as yet unspecified genes affecting the stress
      response and pathogenesis expression. To get insights into the regulatory role(s)
      of LeuO, Genomic SELEX screening has been performed to identify the whole set of
      its regulation targets. A total of 140 LeuO-binding sites were identified on the
      E. coli genome, of which as many as 133 (95%) were found to contain the binding
      sites of H-NS, the universal silencer of stress-response genes, supporting the
      concept that LeuO plays an antagonistic role with anti-silencing activity.
      Western blot analysis indicated that H-NS predominates in growing phase; however,
      after prolonged culture for 1 week, H-NS decreased instead LeuO increased,
      supporting the anti-silencing role of LeuO. In concert with this model, a set of
      stress-response genes including cryptic chaperone/usher-type fimbriae operons are
      under the control of antagonistic interplay between LeuO and H-NS. Confocal laser
      scanning microscopic observation in flow-chambers showed that the mutants lacking
      leuO and some fimbriae genes are defective in biofilm formation or form altered
      biofilm architecture. Taken together we propose that LeuO is a major player in
      antagonistic interplay against the universal silencer H-NS.

PMID- 21883528
TI  - MamK, a bacterial actin, forms dynamic filaments in vivo that are regulated by
      the acidic proteins MamJ and LimJ.
AB  - Bacterial actins, in contrast to their eukaryotic counterparts, are highly
      divergent proteins whose wide-ranging functions are thought to correlate with
      their evolutionary diversity. One clade, represented by the MamK protein of
      magnetotactic bacteria, is required for the subcellular organization of
      magnetosomes, membrane-bound organelles that aid in navigation along the earth's
      magnetic field. Using a fluorescence recovery after photobleaching assay in
      Magnetospirillum magneticum AMB-1, we find that, like traditional actins, MamK
      forms dynamic filaments that require an intact NTPase motif for their turnover in
      vivo. We also uncover two proteins, MamJ and LimJ, which perform a redundant
      function to promote the dynamic behaviour of MamK filaments in wild-type cells.
      The absence of both MamJ and LimJ leads to static filaments, a disrupted
      magnetosome chain, and an anomalous build-up of cytoskeletal filaments between
      magnetosomes. Our results suggest that MamK filaments, like eukaryotic actins,
      are intrinsically stable and rely on regulators for their dynamic behaviour, a
      feature that stands in contrast to some classes of bacterial actins characterized
      to date.

PMID- 21883530
TI  - The effect of the addition of daily fruit and nut bars to diet on weight, and
      cardiac risk profile, in overweight adults.
AB  - BACKGROUND: The frequency of unhealthful snacking has increased dramatically over
      the last three decades. Fruits and nuts have been shown to have positive health
      effects. No study has investigated the aggregate effects of various fruits
      combined with nuts in the form of snack bars on cardiovascular risk factors. The
      aim of this randomised trial was to investigate the effects of a fruit and nut
      snack bar on anthropomorphic measures, lipid panel and blood pressure in
      overweight adults. METHODS: Ninety-four overweight adults (body mass index > 25
      kg m(-2)) were randomly assigned to add two fruit and nut bars totalling 1421.9
      kJ (340 kcal) to their ad libitum diet (intervention group) or to continue with
      their ad libitum diet (control group). Subjects underwent assessment for weight
      (primary outcome measure), as well as waist circumference, lipid panel and blood
      pressure (secondary outcome measures), before and at the end of the 8-week
      treatment. RESULTS: Weight did not change from baseline after snack bar addition
      compared to controls (P = 0.44). Waist circumference (P = 0.69), blood pressure
      (systolic, P = 0.83; diastolic, P = 0.79) and blood lipid panel (total
      cholesterol, P = 0.72; high-density lipoprotein, P = 0.11; total cholesterol/high
      density lipoprotein, P = 0.37; triglycerides, P = 0.89; low-density lipoprotein,
      P = 0.81) also did not change from baseline compared to controls. CONCLUSIONS:
      Two daily fruit and nut bars, totalling 1421.9 kJ (340 kcal), did not cause
      weight gain. The role of habitual snacking on nutrient dense and satiating foods
      on both weight over time, and diet quality, warrants further study. Satiating
      snacks rich in fibre may provide a means to weight stabilisation.

PMID- 21883531
TI  - Effects of the alpha-2 adrenoceptor agonist guanfacine on attention and working
      memory in aged non-human primates.
AB  - Alpha-2 adrenergic receptors are potential targets for ameliorating cognitive
      deficits associated with aging as well as certain pathologies such as attention
      deficit disorder, schizophrenia and Parkinson's disease. Although the alpha-2
      agonist guanfacine has been reported to improve working memory in aged primates,
      it has been difficult to assess the extent to which these improvements may be
      related to drug effects on attention and/or memory processes involved in task
      performance. The present study investigated effects of guanfacine on specific
      attention and memory tasks in aged monkeys. Four Rhesus monkeys (18-21 years old)
      performed a sustained attention (continuous performance) task and spatial working
      memory task (self-ordered spatial search) that has minimal demands on attention.
      Effects of a low (0.0015 mg/kg) and high (0.5 mg/kg) dose of gunafacine were
      examined. Low-dose guanfacine improved performance on the attention task [i.e.
      decreased omission errors by 50.8 +/- 4.3% (P = 0.001) without an effect on
      commission errors] but failed to improve performance on the spatial working
      memory task. The high dose of guanfacine had no effects on either task.
      Guanfacine may have a preferential effect on some aspects of attention in normal
      aged monkeys and in doing so may also improve performance on other tasks,
      including some working memory tasks that have relatively high attention demands.

PMID- 21883532
TI  - Fast food and take-away food consumption are associated with different lifestyle
      characteristics.
AB  - BACKGROUND: One of the most prominent characteristics of fast food and take-away
      food is that it is convenient, meaning that it saves time, it reduces the
      required effort for food provisioning and culinary skills are transferred.
      Studies that investigate the unique effect of these factors on dietary behaviours
      are lacking. Therefore, the present study aimed to examine the associations of
      time, effort, time spent cooking and cooking skills with fast food and take-away
      food consumption. METHODS: Between May and June 2009, a random postal survey was
      sent out to 2323 Swiss households. The response rate was 44% (n = 1017). Spearman
      rank correlations and logistic regression analysis were used to determine the
      multiple relationships of fast food and take-away food intake with gender, age,
      educational level, income, mental effort, physical effort, working status,
      cooking skills and time spent cooking. RESULTS: Fast food consumption was found
      to be associated with gender (males) [odds ratio (OR) = 1.61, P < 0.05], age (40
      59 years) (OR = 0.41, P < 0.001), age (>=60 years) (OR = 0.13, P < 0.001), time
      spent cooking (OR = 0.99; P < 0.01) and cooking skills (OR = 0.81, P < 0.05).
      Take-away food consumption was found to be associated with gender (males) (OR =
      1.86, P < 0.01), age (40-59 years) (OR = 0.58, P < 0.01), age (>=60 years) (OR =
      0.28, P < 0.001), income (OR = 1.11, P <0.01), education (middle) (OR = 0.65, P <
      0.05) and mental effort (OR = 1.25, P < 0.05). CONCLUSIONS: Take-away and fast
      food consumption are behaviours that share the same demographic determinants of
      age and gender, although they are influenced by different life style
      determinants. It is very likely that motivations related to time, effort and
      cooking are of increasing importance for food decisions in our society.

PMID- 21883533
TI  - Responses to corticotrophin-releasing hormone and dexamethasone in a large series
      of human adrenocorticotrophic hormone-secreting pituitary adenomas in vitro
      reveal manifold corticotroph tumoural phenotypes.
AB  - Patients with Cushing's disease are known to present a variable secretory
      response to stimulatory and inhibitory challenges. Evaluation of the secretory
      behaviour of pituitary adrenocorticotrophic hormone (ACTH)-secreting adenomas in
      vitro aids in the comprehension of its behaviour in vivo; however, given the
      small size of these tumours and the consequent paucity of material available to
      in vitro studies, a comprehensive study on the secretory behaviour of human
      corticotroph tumours has not yet been performed. The present study aimed to
      assess the spectrum of responses to the two main corticotroph modulators,
      corticotrophin-releasing hormone (CRH) and dexamethasone, in a large series of
      human ACTH-secreting pituitary tumours. Seventy-two ACTH-secreting pituitary
      tumours were collected during surgery and established in culture. Specimens were
      incubated with 10 nm CRH and/or 10 nm dexamethasone for 4 h and 24 h. Secretion
      in unstimulated, control wells was set at 100% and changes in ACTH concentrations
      by at least 20% were considered as responses. Parallel experiments in 12 rat
      anterior pituitary primary cultures were evaluated. A marked ACTH increase was
      observed during incubation with CRH in 70% of tumoural specimens at 4 h (range
      124-3500% of control wells) and in 57% at 24 h (range 122-3323%). Dexamethasone
      reduced ACTH secretion in almost 50% of tumours (range 78-2% of control at 4 h;
      76-3% at 24 h), whereas it did not affect ACTH medium levels in 30% of specimens
      and induced a paradoxical ACTH increase in 20% of tumours (range 130-327% of
      control at 4 h; 156-348% at 24 h). By comparison, CRH uniformly increased ACTH
      levels in rat anterior pituitary primary cultures (mean 745 +/- 84% at 4 h; 347
      +/- 25% at 24 h), whereas dexamethasone decreased ACTH levels by 40-50% in all
      experiments. In conclusion, the present study of a large series of human ACTH
      secreting pituitary tumours in vitro revealed a considerable variability in the
      responses to CRH and dexamethasone. This finding indicates the existence of
      multiple corticotroph tumoural phenotypes and may account for the different
      responses to physiological and pharmacological modulators in vivo.

PMID- 21883534
TI  - Adipose zinc-alpha2-glycoprotein is a catabolic marker in cancer and noncancerous
      states.
AB  - OBJECTIVE: Zinc-alpha2-glycoprotein (ZAG) has been proposed as a tumour-derived
      cancer cachexia factor. However, ZAG is produced by some normal tissues,
      including white adipose tissue (WAT), and high serum ZAG levels are present in
      nonmalignant conditions. We determined whether human WAT contributes to serum ZAG
      levels and how serum and WAT-secreted ZAG levels correlate with catabolism in
      patients with cancer and in obese subjects undergoing a very low-calorie diet
      (VLCD) for 11 days. DESIGN/SUBJECTS: ZAG levels in serum and in conditioned
      medium from WAT/adipocytes were determined by enzyme-linked immunosorbent assay.
      ZAG release from WAT in vivo was determined in 10 healthy subjects. The
      correlation between ZAG and cachexia was studied in 34 patients with newly
      diagnosed gastrointestinal cancer. The impact of a VLCD on ZAG release and serum
      levels was assessed in 10 obese women. RESULTS: ZAG was released from abdominal
      WAT and adipocytes in vitro. However, the arteriovenous differences in vivo
      showed that there was no significant contribution of WAT to the circulating
      levels. WAT-secreted but not serum ZAG correlated positively with poor
      nutritional status but not with fat mass (or body mass index) in patients with
      gastrointestinal cancer. In obese subjects on a VLCD, ZAG secretion from WAT
      increased significantly whereas serum levels remained unaltered. CONCLUSIONS: 
      ZAG is released from human WAT, but this tissue does not contribute significantly
      to the circulating levels. WAT-secreted ZAG correlates with nutritional status
      but not with fat mass in both cancer and nonmalignant conditions. Adipose ZAG is
      therefore a local factor activated primarily by the catabolic state per se.

PMID- 21883536
TI  - Inflammatory and haemostatic markers in idiopathic intracranial hypertension.

PMID- 21883537
TI  - beta2 -adrenergic receptor Thr164IIe polymorphism, blood pressure and ischaemic
      heart disease in 66 750 individuals.
AB  - OBJECTIVES: The beta(2) -adrenergic receptor (ADRB2) is located on smooth muscle
      cells and is an important regulator of smooth muscle tone. The Thr164Ile
      polymorphism (rs1800888) in the ADRB2 gene is rare but has profound functional
      consequences on receptor function and could cause lifelong elevated smooth muscle
      tone. We tested the hypothesis that Thr164Ile is associated with increased blood
      pressure, increased frequency of hypertension and increased risk of
      cardiovascular disease (CVD). SUBJECTS: A total of 66 750 individuals from two
      large Danish general population studies were genotyped, and 1943 Thr164Ile
      heterozygotes and 16 homozygotes were identified. RESULTS: Thr164Ile genotype was
      associated with increased systolic and diastolic blood pressure in women (trend:
      P = 0.04 and 0.02): systolic and diastolic blood pressure increased by 5% and 2%,
      respectively, in female homozygotes compared with female noncarriers. All female
      Thr164Ile homozygotes had hypertension compared with 58% of female heterozygotes
      and 54% of female noncarriers (chi-square: P = 0.001). Female Thr164Ile
      homozygotes and heterozygotes had odds ratios for ischaemic heart disease (IHD)
      of 2.93 (0.56-15.5) and 1.28 (1.03-1.61), respectively, compared with female
      noncarriers (trend: P = 0.007). These differences were not observed in men.
      Furthermore, Gly16Arg (rs1042713) and Gln27Glu (rs1042714) in the ADRB2 gene were
      not associated with blood pressure, hypertension or CVD either in the population
      overall or in women and men separately. CONCLUSIONS: ADRB2 Thr164Ile is
      associated with increased blood pressure, increased frequency of hypertension and
      increased risk of IHD amongst women in the general population. These findings,
      particularly for homozygotes, are novel.

PMID- 21883539
TI  - Fine needle aspiration cytology in ovarian lesions: an institutional experience
      of 584 cases.
AB  - OBJECTIVE: To assess the diagnostic value of fine needle aspiration cytology
      (FNAC) in ovarian lesions. METHODS: This was a retrospective study of ultrasound
      guided (US) FNAC of 584 ovarian lesions from January 1998 to July 2010. The
      lesions were categorized into non-neoplastic lesions, neoplastic lesions and
      inadequate aspirates. The results were compared with the corresponding
      histopathology whenever available. RESULTS:  Of the 584 lesions, 180 (30.8%) were
      reported as non-neoplastic (48 non-specific inflammation, 11 tuberculosis, 63
      functional cysts and 58 endometriotic cysts), 249 (42.6%) as neoplastic (81
      benign lesions/tumours and 168 malignant) and 155 (26.5%) as inadequate. Based on
      the subsequent histopathology, which was available in 121 (20.7%), the cases were
      divided into those that were concordant and discordant. Concordant cases
      comprised 92/121 (76%), including 28 non-neoplastic lesions (seven non-specific
      inflammation, nine functional cysts and 12 endometriotic cysts), 42 surface
      epithelial tumours (13 benign and 29 malignant), 10 germ cell tumours (five
      mature cystic teratomas and five mixed germ cell tumours), seven sex-cord stromal
      tumours (three granulosa cell tumours, one sclerosing stromal tumour, one strumal
      leutoma, one Sertoli Leydig cell tumour and one malignant Sertoli cell tumour)
      and five miscellaneous lesions (one plasma cell tumour, two leiomyosarcomas and
      two cases of necrosis). Discordant cases comprised 29/121 (24%) (21were
      inconclusive or inadequate on cytology), including four endometriotic cysts, 14
      surface epithelial tumours (one cystadenofibroma, one borderline mucinous tumour
      and 12 carcinomas), five germ cell tumours (two immature teratomas and three
      mature cystic teratomas), two thecomas, one fibroma, one sclerosing stromal
      tumour, one fibrosarcoma and one myxoma. FNAC sensitivity for a diagnosis of
      malignancy was 85.7%, specificity 98.0%, positive predictive value 97.7%,
      negative predictive value 87.7% and accuracy 92.0%, if 21 inconclusive/inadequate
      FNACs were excluded; with the latter taken as false negatives, sensitivity was
      73.7% and accuracy 76.0%. CONCLUSION:   FNAC has a high specificity for diagnosis
      of ovarian/adnexal lesions but greater experience is required for the accurate
      subtyping of neoplasms and sensitivity is limited by inconclusive/inadequate
      results.

PMID- 21883538
TI  - Desensitization regimens for drug allergy: state of the art in the 21st century.
AB  - Adverse reactions to drugs are increasingly being recognized as important
      contributions to disease in their own right as well as impediments to the best
      treatment of various conditions, including infectious, autoimmune, and neoplastic
      maladies. Rapid drug desensitization (RDD) is an effective mechanism for safely
      administering important medications while minimizing or entirely circumventing
      such adverse reactions in sensitized patients. We reviewed the literature on RDD
      in the last 10 years, including our experience from the Brigham and Women's
      Hospital Desensitization Program with hundreds of patients desensitized to a
      broad variety of drugs. RDD in our programme has been uniformly successful in
      patients with hypersensitivity reactions to antibiotics, chemotherapeutics, and
      monoclonal antibodies. Any reactions that occur during desensitization are
      generally much less severe than the initial hypersensitivity reaction to the
      drug, and patients have received the full dose of the desired medication 99.9% of
      the time out of (796) desensitizations. To date, there have been no fatalities.
      RDD is a safe and highly effective method for treating sensitized patients with
      the optimal pharmacologic agents. Its use should be expanded, but because patient
      safety is paramount, protocols must be created, reviewed, and overseen by
      allergist-immunologists with special training and experience in modern techniques
      of desensitization.

PMID- 21883535
TI  - Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance
      and fatty liver in a nondiabetic healthy population.
AB  - OBJECTIVES: Insulin resistance is associated with increased CD36 expression in a
      number of tissues. Moreover, excess macrophage CD36 may initiate atherosclerotic
      lesions. The aim of this study was to determine whether plasma soluble CD36
      (sCD36) was associated with insulin resistance, fatty liver and carotid
      atherosclerosis in nondiabetic subjects. METHODS: In 1296 healthy subjects
      without diabetes or hypertension recruited from 19 centres in 14 European
      countries (RISC study), we determined the levels of sCD36, adiponectin, lipids
      and liver enzymes, insulin sensitivity (M/I) by euglycaemic-hyperinsulinaemic
      clamp, carotid atherosclerosis as intima-media thickness (IMT) and two estimates
      of fatty liver, the fatty liver index (FLI) and liver fat percentage (LF%).
      RESULTS: IMT, FLI, LF%, presence of the metabolic syndrome, impaired glucose
      regulation, insulin and triglycerides increased across sCD36 quartiles (Q2-Q4),
      whereas adiponectin and M/I decreased (P <= 0.01). sCD36 was lower in women than
      in men (P = 0.045). Log sCD36 showed a bimodal distribution, and amongst subjects
      with sCD36 within the log-normal distribution (log-normal population, n = 1029),
      sCD36 was increased in subjects with impaired glucose regulation (P = 0.045),
      metabolic syndrome (P = 0.006) or increased likelihood of fatty liver (P <
      0.001). sCD36 correlated significantly with insulin, triglycerides, M/I and FLI
      (P < 0.05) after adjustment for study centre, gender, age, glucose tolerance
      status, smoking habits and alcohol consumption. In the log-normal population,
      these relationships were stronger than in the total study population and,
      additionally, sCD36 was significantly associated with LF% and IMT (P < 0.05).
      CONCLUSIONS: In this cross-sectional study of nondiabetic subjects, sCD36 was
      significantly associated with indices of insulin resistance, carotid
      atherosclerosis and fatty liver. Prospective studies are needed to further
      evaluate the role of sCD36 in the inter-relationship between atherosclerosis,
      fatty liver and insulin resistance.

PMID- 21883540
TI  - Reactive tubal epithelium mimicking Mullerian serous carcinoma: pitfalls in the
      evaluation of pelvic wash specimens.

PMID- 21883541
TI  - Fine needle aspiration cytology of a granular cell tumour arising in the thyroid
      gland.

PMID- 21883542
TI  - Fine needle aspiration cytology of metastatic polymorphous low-grade
      adenocarcinoma of the palate in a cervical lymph node.

PMID- 21883543
TI  - Humoral immunomodulatory effect of influenza vaccine in potential blood donors:
      implications for transfusion safety.
AB  - BACKGROUND: Generalised immune stimulation may follow vaccination causing
      increased antibody titres of nonvaccine-related antibodies or bystander
      antibodies, including those to human leukocyte antigens (HLA) and ABO blood group
      antigens. HLA antibodies may lead to transfusion-related acute lung injury. High
      titre ABO antibodies may cause acute haemolytic transfusion reactions after
      plasma-incompatible platelet transfusion. It is unknown if these antibodies can
      be stimulated by vaccination in otherwise normal subjects. METHODS: Blood samples
      of healthy volunteers who received the 2009 influenza vaccine were analysed for
      HLA and ABO antibodies before and 14 days after vaccination (n = 86). Age, gender
      and history of exposure to foreign tissue, through pregnancy, blood transfusion
      or tissue transplant were collected. Results were analysed with descriptive
      statistics, paired t-test and chi(2) test. RESULTS: There was no increase in HLA
      or ABO antibody levels after vaccination (P = not significant). Forty per cent of
      subjects (n = 35) had previously formed HLA antibody and 16% (7 males and 7
      females) had HLA sensitisation but did not report foreign tissue exposure. The
      average panel reactive antibody of the HLA sensitised but nonexposed subjects was
      lower in males than females (3.4 and 28.6%, respectively, P = 0.015, t-test),
      suggesting that some females may have had unrecognised pregnancy. CONCLUSIONS:
      HLA or ABO antibodies did not appear to be stimulated by the 2009 influenza
      vaccine. Female blood donors with putatively unrecognised pregnancies may have
      higher risk for HLA sensitisation than previously thought. Further study using
      different vaccine formulations may lead to better understanding of the risks of
      bystander antibodies in the blood donor population.

PMID- 21883544
TI  - A case of a canine pigmented plaque associated with the presence of a Chi
      papillomavirus.
AB  - The seven fully described canine papillomaviruses (CPVs) have been allocated by
      sequence comparison and other genetic features into three phylogenetic clades.
      This largely reflects clinical findings, so each sequence of a newly discovered
      CPV in combination with clinical and pathological details is a valuable piece of
      evidence. We hypothesize that the genomic sequence of a new CPV can help to
      predict clinical features and progression, and that this can be tested in
      subsequent cases. In this case, a 2-year-old female dachshund-mix presented with
      papillomatosis clinically and histologically characterized as pigmented viral
      plaques. PCRs using primers evaluated for CPVs successfully amplified
      papillomavirus (PV) DNA. Sequencing of the products revealed an unknown PV
      putatively belonging to the PV genus Chi. Rolling circle amplification was used
      to amplify the entire viral genome. Sequencing revealed a novel PV, designated as
      CPV8, which was most closely related (63% homology) to the recently discovered
      CPV4. CPV4 is associated with benign pigmented plaques in pugs. Phylogenetic
      analysis based on the nucleotide sequences of four viral genes showed that the
      novel virus was closest to CPV3, CPV4 and CPV5. The presence of viral DNA was
      confirmed in the lesions by in situ hybridization using specific probes. CPV8 may
      consequently be regarded as the fourth member of the Chi-papillomavirus genus.
      All viruses belonging to this genus induce pigmented plaques in dogs. These
      findings support the hypothesis that genomic sequences can be useful in
      predicting the clinical features of CPV infection.

PMID- 21883545
TI  - A case of xanthoma in a Saanen goat.
AB  - This report describes a case of a subcutaneous xanthoma of the sacral region in a
      2-year-old female Saanen goat. The tan-coloured mass was 8.5 cm * 4.0 cm * 0.5 cm
      in size. Yellow-white areas were present across the cut surface.
      Histopathologically, the mass was composed of foamy macrophages, numerous giant
      cells, abundant lipid material and cholesterol clefts. The structure consisted of
      lobular areas surrounded by a stroma. Tissue sections were negative for bacteria,
      fungi and mycobacteria. Frozen tissue from the mass stained positively with Oil
      Red O, confirming lipid accumulation in both the extracellular spaces and the
      large foamy macrophages. Immunohistochemically, the mass was positive for
      vimentin, proliferating cell nuclear antigen and CD68, but negative for smooth
      muscle actin, glial fibrillary acidic protein and S100 protein antibodies. As the
      animal was presented dead, it was not possible to analyse blood lipid levels. To
      the authors' knowledge, this is the first report of a xanthoma in a goat.

PMID- 21883546
TI  - Self-harm and attempted suicide among therapeutic community admissions.
AB  - INTRODUCTION AND AIMS: The study aimed to determine the histories of self-harm
      and attempted suicide among therapeutic community entrants by primary presenting
      substance problem, and to determine predictors of these behaviours. DESIGN AND
      METHODS: One hundred and eighty-eight consecutive new treatment admissions to We
      Help Ourselves drug-free treatment services were administered a structured
      interview. RESULTS: Lifetime histories of self-harm were reported by 34% (9%
      within the preceding year), and 20% had done so on multiple occasions. Just over
      one-third reported a lifetime history of attempted suicide (15% within the
      preceding year), and 17% reported multiple attempts. There were no significant
      bivariate associations between primary drug and either behaviour. Multivariate
      analyses indicated that the alcohol and opioid groups were significantly more
      likely than the cannabis group to have a history of self-harm, but did not differ
      from each other or the psychostimulant group. Other independent correlates of
      self-harm were female gender, lifetime PTSD diagnosis, younger age at first
      intoxication and a history of attempted suicide. In multivariate analyses, the
      alcohol and opioid groups were significantly less likely than the cannabis group
      to have a history of attempted suicide, but did not differ from each other or the
      psychostimulant group. Other significant correlates of attempted suicide were
      female gender and a history of self-harm. DISCUSSION AND CONCLUSIONS: Both self
      harm and suicide attempts were highly prevalent, and strongly associated with
      each other. Moreover, there were few differences between primary drug problems.
      All entrants should be screened for these behaviours, and appropriate responses
      implemented.

PMID- 21883547
TI  - The pyruvate, orthophosphate dikinase regulatory proteins of Arabidopsis are both
      bifunctional and interact with the catalytic and nucleotide-binding domains of
      pyruvate, orthophosphate dikinase.
AB  - Pyruvate orthophosphate dikinase (PPDK) is a key enzyme in C(4)  photosynthesis
      and is also found in C(3)  plants. It is post-translationally modified by the
      PPDK regulatory protein (RP) that possesses both kinase and phosphotransferase
      activities. Phosphorylation and dephosphorylation of PPDK lead to inactivation
      and activation respectively. Arabidopsis thaliana contains two genes that encode
      chloroplastic (RP1) and cytosolic (RP2) isoforms of RP, and although RP1 has both
      kinase and phosphotransferase activities, to date RP2 has only been shown to act
      as a kinase. Here we demonstrate that RP2 is able to catalyse the
      dephosphorylation of PPDK, although at a slower rate than RP1 under the
      conditions of our assay. From yeast two-hybrid analysis we propose that RP1 binds
      to the central catalytic domain of PPDK, and that additional regions towards the
      carboxy and amino termini are required for a stable interaction between RP2 and
      PPDK. For 21 highly conserved amino acids in RP1, mutation of 15 of these reduced
      kinase and phosphotransferase activity, while mutation of six residues had no
      impact on either activity. We found no mutant in which only one activity was
      abolished. However, in some chimaeric fusions that comprised the amino and
      carboxy termini of RP1 and RP2 respectively, the kinase reaction was severely
      compromised but phosphotransferase activity remained unaffected. These findings
      are consistent with the findings that both RP1 and RP2 modulate reversibly the
      activity of PPDK, and possess one bifunctional active site or two separate sites
      in close proximity.

PMID- 21883548
TI  - Cellulose synthesis via the FEI2 RLK/SOS5 pathway and cellulose synthase 5 is
      required for the structure of seed coat mucilage in Arabidopsis.
AB  - The seeds of Arabidopsis thaliana and many other plants are surrounded by a
      pectinaceous mucilage that aids in seed hydration and germination. Mucilage is
      synthesized during seed development within maternally derived seed coat mucilage
      secretory cells (MSCs), and is released to surround the seed upon imbibition. The
      FEI1/FEI2 receptor-like kinases and the SOS5 extracellular GPI-anchored protein
      were shown previously to act on a pathway that regulates the synthesis of
      cellulose in Arabidopsis roots. Here, we demonstrate that both FEI2 and SOS5 also
      play a role in the synthesis of seed mucilage. Disruption of FEI2 or SOS5 leads
      to a reduction in the rays of cellulose observed across the seed mucilage inner
      layer, which alters the structure of the mucilage in response to hydration.
      Mutations in CESA5, which disrupts an isoform of cellulose synthase involved in
      primary cell wall synthesis, result in a similar seed mucilage phenotype. The
      data indicate that CESA5-derived cellulose plays an important role in the
      synthesis and structure of seed coat mucilage and that the FEI2/SOS5 pathway
      plays a role in the regulation of cellulose synthesis in MSCs. Moreover, these
      results establish a novel structural role for cellulose in anchoring the pectic
      component of seed coat mucilage to the seed surface.

PMID- 21883549
TI  - Overexpression of Arabidopsis thaliana PTEN caused accumulation of autophagic
      bodies in pollen tubes by disrupting phosphatidylinositol 3-phosphate dynamics.
AB  - Autophagy is a pathway in eukaryotes by which nutrient remobilization occurs
      through bulk protein and organelle turnover. Autophagy not only aides cells in
      coping with harsh environments but also plays a key role in many physiological
      processes that include pollen germination and tube growth. Most autophagic
      components are conserved among eukaryotes, but phylum-specific molecular
      components also exist. We show here that Arabidopsis thaliana PTEN, a protein and
      lipid dual phosphatase homologous to animal PTENs (phosphatase and tensin
      homologs deleted on chromosome 10), regulates autophagy in pollen tubes by
      disrupting the dynamics of phosphatidylinositol 3-phosphate (PI3P). The pollen
      specific PTEN bound PI3P in vitro and was localized at PI3P-positive vesicles.
      Overexpression of PTEN caused accumulation of autophagic bodies and resulted in
      gametophytic male sterility. Such an overexpression effect was dependent upon its
      lipid phosphatase activity and was inhibited by exogenous PI3P or by expression
      of a class III phosphatidylinositol 3-kinase (PI3K) that produced PI3P.
      Overexpression of PTEN disrupted the dynamics of autophagosomes and a
      subpopulation of endosomes, as shown by altered localization patterns of
      respective fluorescent markers. Treatment with wortmannin, an inhibitor of class
      III PI3K, mimicked the effects by PTEN overexpression, which implied a critical
      role for PI3P dynamics in these processes. Despite sharing evolutionarily
      conserved catalytic domains, plant PTENs contain regulatory sequences that are
      distinct from those of animal PTENs, which might underlie their differing
      membrane association and thereby function. Our results show that PTEN regulates
      autophagy through phylum-specific molecular mechanisms.

PMID- 21883550
TI  - Chromosomal rearrangements between tomato and Solanum chilense hamper mapping and
      breeding of the TYLCV resistance gene Ty-1.
AB  - Tomato yellow leaf curl disease, a devastating disease of Solanum lycopersicum
      (tomato), is caused by a complex of begomoviruses generally referred to as Tomato
      yellow leaf curl virus (TYLCV). Almost all breeding for TYLCV resistance has been
      based on the introgression of the Ty-1 resistance locus derived from Solanum
      chilense LA1969. Knowledge about the exact location of Ty-1 on tomato chromosome
      6 will help in understanding the genomic organization of the Ty-1 locus. In this
      study, we analyze the chromosomal rearrangement and recombination behavior of the
      chromosomal region where Ty-1 is introgressed. Nineteen markers on tomato
      chromosome 6 were used in F(2) populations obtained from two commercial hybrids,
      and showed the presence of a large introgression in both. Fluorescence in situ
      hybridization (FISH) analysis revealed two chromosomal rearrangements between S.
      lycopersicum and S. chilense LA1969 in the Ty-1 introgression. Furthermore, a
      large-scale recombinant screening in the two F(2) populations was performed, and
      30 recombinants in the Ty-1 introgression were identified. All recombination
      events were located on the long arm beyond the inversions, showing that
      recombination in the inverted region was absent. Disease tests on progenies of
      informative recombinants with TYLCV mapped Ty-1 to the long arm between markers
      MSc05732-4 and MSc05732-14, an interval overlapping with the reported Ty-3
      region, which led to the indication that Ty-1 and Ty-3 may be allelic. With this
      study we prove that FISH can be used as a diagnostic tool to aid in the accurate
      mapping of genes that were introgressed from wild species into cultivated tomato.

PMID- 21883551
TI  - NAC domain function and transcriptional control of a secondary cell wall master
      switch.
AB  - NAC domain transcription factors act as master switches for secondary cell wall
      thickening, but how they exert their function and how their expression is
      regulated remains unclear. Here we identify a loss-of-function point mutation in
      the NST1 gene of Medicago truncatula. The nst1-3 mutant shows no lignification in
      interfascicular fibers, as previously seen in tnt1 transposon insertion alleles.
      However, the C->A transversion, which causes a T94K mutation in the NST1 protein,
      leads to increased NST1 expression. Introduction of the same mutation into the
      Arabidopsis homolog SND1 causes both protein mislocalization and loss of target
      DNA binding, with a resultant inability to trans-activate downstream secondary
      wall synthesis genes. Furthermore, trans-activation assays show that the
      expression of SND1 operates under positive feedback control from itself, and SND1
      was shown to bind directly to a conserved motif in its own promoter, located
      within a recently described 19-bp secondary wall NAC binding element. Three MYB
      transcription factors downstream of SND1, one of which is directly regulated by
      SND1, exert negative regulation on SND1 promoter activity. Our results identify a
      conserved amino acid critical for NST1/SND1 function, and show that the
      expression of the NAC master switch itself is under both positive
      (autoregulatory) and negative control.

PMID- 21883552
TI  - Arabidopsis DRB4 protein in antiviral defense against Turnip yellow mosaic virus
      infection.
AB  - RNA silencing is an important antiviral mechanism in diverse eukaryotic
      organisms. In Arabidopsis DICER-LIKE 4 (DCL4) is the primary antiviral Dicer,
      required for the production of viral small RNAs from positive-strand RNA viruses.
      Here, we showed that DCL4 and its interacting partner dsRNA-binding protein 4
      (DRB4) participate in the antiviral response to Turnip yellow mosaic virus
      (TYMV), and that both proteins are required for TYMV-derived small RNA
      production. In addition, our results indicate that DRB4 has a negative effect on
      viral coat protein accumulation. Upon infection DRB4 expression was induced and
      DRB4 protein was recruited from the nucleus to the cytoplasm, where replication
      and translation of viral RNA occur. DRB4 was associated with viral RNA in vivo
      and directly interacted in vitro with a TYMV RNA translational enhancer, raising
      the possibility that DRB4 might repress viral RNA translation. In plants the role
      of RNA silencing in viral RNA degradation is well established, but its potential
      function in the regulation of viral protein levels has not yet been explored. We
      observed that severe infection symptoms are not necessarily correlated with
      enhanced viral RNA levels, but might be caused by elevated accumulation of viral
      proteins. Our findings suggest that the control of viral protein as well as RNA
      levels might be important for mounting an efficient antiviral response.

PMID- 21883553
TI  - A rice calcium-dependent protein kinase OsCPK12 oppositely modulates salt-stress
      tolerance and blast disease resistance.
AB  - Calcium-dependent protein kinases (CDPKs) regulate the downstream components in
      calcium signaling pathways. We investigated the effects of overexpression and
      disruption of an Oryza sativa (rice) CDPK (OsCPK12) on the plant's response to
      abiotic and biotic stresses. OsCPK12-overexpressing (OsCPK12-OX) plants exhibited
      increased tolerance to salt stress. The accumulation of hydrogen peroxide (H(2)
      O(2) ) in the leaves was less in OsCPK12-OX plants than in wild-type (WT) plants.
      Genes encoding reactive oxygen species (ROS) scavenging enzymes (OsAPx2 and
      OsAPx8) were more highly expressed in OsCPK12-OX plants than in WT plants,
      whereas the expression of the NADPH oxidase gene, OsrbohI, was decreased in
      OsCPK12-OX plants compared with WT plants. Conversely, a retrotransposon (Tos17)
      insertion mutant, oscpk12, and plants transformed with an OsCPK12 RNA
      interference (RNAi) construct were more sensitive to high salinity than were WT
      plants. The level of H(2) O(2)  accumulation was greater in oscpk12 and OsCPK12
      RNAi plants than in the WT. These results suggest that OsCPK12 promotes tolerance
      to salt stress by reducing the accumulation of ROS. We also observed that OsCPK12
      OX seedlings had increased sensitivity to abscisic acid (ABA) and increased
      susceptibility to blast fungus, probably resulting from the repression of ROS
      production and/or the involvement of OsCPK12 in the ABA signaling pathway.
      Collectively, our results suggest that OsCPK12 functions in multiple signaling
      pathways, positively regulating salt tolerance and negatively modulating blast
      resistance.

PMID- 21883554
TI  - Specific delivery of AtBT1 to mitochondria complements the aberrant growth and
      sterility phenotype of homozygous Atbt1 Arabidopsis mutants.
AB  - It has been shown that homozygous AtBT1::T-DNA Arabidopsis mutants display an
      aberrant growth and sterility phenotype, and that AtBT1 is a carrier that is
      exclusively localized to the inner plastidial envelope and is required for export
      of newly synthesized adenylates into the cytosol. However, a recent demonstration
      that AtBT1 is localized to both plastids and mitochondria suggested that
      plastidic AtBT1 is not necessary for normal growth and fertility of Arabidopsis.
      To test this hypothesis, we produced and characterized homozygous AtBT1::T-DNA
      mutants stably expressing either dually localized AtBT1 or AtBT1 specifically
      localized to the mitochondrial compartment. These analyses revealed that the
      aberrant growth and sterility phenotype of homozygous AtBT1::T-DNA mutants was
      complemented when expressing both the dual-targeted AtBT1 and AtBT1 specifically
      delivered to mitochondria. These data confirm that (i) plastidic AtBT1 is not
      strictly required for normal growth and fertility of the plant, and (ii) specific
      delivery of AtBT1 to mitochondria is enough to complement the aberrant growth and
      sterility phenotype of homozygous AtBT1::T-DNA mutants. Furthermore, data
      presented here question the idea that the requirement for AtBT1 is due to its
      involvement in transport of newly synthesized adenylates from the plastid to the
      cytosol, and suggest that the protein may play as yet unidentified functions in
      plastids and mitochondria.

PMID- 21883555
TI  - Arabidopsis glabra2 mutant seeds deficient in mucilage biosynthesis produce more
      oil.
AB  - Seed oil, one of the major seed storage compounds in plants, is of great economic
      importance for human consumption, as an industrial raw material and as a source
      of biofuels. Thus, improving the seed oil yield in crops is an important
      objective. The GLABRA2 (GL2) gene in Arabidopsis thaliana encodes a transcription
      factor that is required for the proper differentiation of several epidermal cell
      types. GL2 has also been shown to regulate seed oil levels, as a loss-of-function
      mutation in the GL2 gene results in plants with a higher seed oil content than
      wild-type. We have extended this observation by showing that loss-of-function
      mutations in several positive regulators of GL2 also result in a high seed oil
      phenotype. The GL2 gene is expressed in both the seed coat and embryo, but the
      embryo is the main site of seed oil accumulation. Surprisingly, our results
      indicate that it is loss of GL2 activity in the seed coat, not the embryo, that
      contributes to the high seed oil phenotype. One target of GL2 in the seed coat is
      the gene MUCILAGE MODIFIED 4 (MUM4), which encodes a rhamnose synthase that is
      required for seed mucilage biosynthesis. We found that mum4 mutant seeds, like
      those of gl2 mutants, have an increased seed oil content in comparison with wild
      type. Therefore, GL2 regulates seed oil production at least partly through its
      influence on MUM4 expression in the seed coat. We propose that gl2 mutant seeds
      produce more oil due to increased carbon allocation to the embryo in the absence
      of seed coat mucilage biosynthesis.

PMID- 21883556
TI  - Multiple Arabidopsis genes primed for recruitment into C4 photosynthesis.
AB  - C(4)  photosynthesis occurs in the most productive crops and vegetation on the
      planet, and has become widespread because it allows increased rates of
      photosynthesis compared with the ancestral C(3)  pathway. Leaves of C(4)  plants
      typically possess complicated alterations to photosynthesis, such that its
      reactions are compartmented between mesophyll and bundle sheath cells. Despite
      its complexity, the C(4)  pathway has arisen independently in 62 separate
      lineages of land plants, and so represents one of the most striking examples of
      convergent evolution known. We demonstrate that elements in untranslated regions
      (UTRs) of multiple genes important for C(4)  photosynthesis contribute to the
      metabolic compartmentalization characteristic of a C(4)  leaf. Either the 5' or
      the 3' UTR is sufficient for cell specificity, indicating that functional
      redundancy underlies this key aspect of C(4)  gene expression. Furthermore, we
      show that orthologous PPDK and CA genes from the C(3)  plant Arabidopsis thaliana
      are primed for recruitment into the C(4)  pathway. Elements sufficient for M-cell
      specificity in C(4)  leaves are also present in both the 5' and 3' UTRs of these
      C(3) A. thaliana genes. These data indicate functional latency within the UTRs of
      genes from C(3)  species that have been recruited into the C(4)  pathway. The
      repeated recruitment of pre-existing cis-elements in C(3)  genes may have
      facilitated the evolution of C(4)  photosynthesis. These data also highlight the
      importance of alterations in trans in producing a functional C(4)  leaf, and so
      provide insight into both the evolution and molecular basis of this important
      type of photosynthesis.

PMID- 21883557
TI  - Removing allosteric feedback inhibition of tomato 4-coumarate:CoA ligase by
      directed evolution.
AB  - Plant secondary metabolites, such as those derived from the phenylpropanoid
      pathway, have a beneficial effect on human health. Manipulation of metabolic flux
      in the phenylpropanoid pathway is important for achieving enhanced production of
      compounds such as anthocyanins, flavonoids and isoflavonoids. Here, we describe
      the development of a high-throughput molecular evolution approach that can be
      used for catalytic improvement of at least four key phenylpropanoid pathway
      enzymes, within the context of the metabolic pathway. This method uses yeast
      cells that express plant phenylpropanoid pathway enzymes, leading to formation of
      a colored intermediate that can be used as a readout in high-throughput
      screening. Here we report the identification of improved tomato peel 4
      coumarate:CoA ligase variants using this approach. We found that the wild-type
      enzyme is strongly allosterically inhibited by naringenin, a downstream product
      of the pathway. Surprisingly, at least two of the improved variants are
      completely insensitive to feedback inhibition by naringenin. We suggest that this
      inhibition is exerted through a unique and previously unrecognized allosteric
      domain.

PMID- 21883558
TI  - Prevalence of molar-incisor hypomineralisation observed using transillumination
      in a group of children from Barcelona (Spain).
AB  - OBJECTIVES: The objectives were to investigate the prevalence of the condition,
      by using transillumination, in a group of children. Analysed the prevalence with
      regard to gender, jaw affected, and the teeth that exhibited dysplasia most
      commonly. METHODS: A sample of 550 children aged 6 to 14 years was selected at
      the Department of Paediatric Dentistry at the Universitat Internacional de
      Catalunya, but among those selected only 505 children were eligible for inclusion
      in the study. The gender and age of the child, number of permanent teeth, number
      of teeth affected by MIH and their position were registered. RESULTS: Ninety
      patients (17.85%) had MIH. Of these, 45 were girls (50%) and 45 were boys (50%).
      A total of 8062 permanent teeth were observed. Of these, 344 (4.2%) were affected
      by MIH. Of the teeth affected, 198 (57.7%) were located in the maxilla and 146
      (42.4%) in the mandible. This result was statistically significant (P = 0.003).
      CONCLUSIONS: The population studied showed a prevalence of MIH of 17.8%. The
      presence of the defect did not differ according to sex in this population.
      Defects were more common among teeth in the maxilla.

PMID- 21883559
TI  - Effect of a calcium hydroxide/chlorhexidine paste as intracanal dressing in human
      primary teeth with necrotic pulp against Porphyromonas gingivalis and
      Enterococcus faecalis.
AB  - BACKGROUND: Intracanal medication is important for endodontic treatment success
      as it eliminates microorganisms that persist after biomechanical preparation.
      Aim.  To evaluate the effect of two intracanal medications against Porphyromonas
      gingivalis and Enterococcus faecalis in the root canals of human primary teeth
      with necrotic pulp with and without furcal/periapical lesion, using quantitative
      real-time polymerase chain reaction (qRT-PCR). DESIGN: Thirty-two teeth with
      necrotic pulp were used. Twelve teeth did not present lesion, and 20 teeth
      presented radiographically visible furca/periapical lesion. Microbiological
      samples were collected after coronal access and biomechanical preparation. The
      teeth were medicated with calcium hydroxide pastes prepared with either
      polyethylene glycol or chlorhexidine. After 30days, the medication was removed
      and a third collection was performed. Microbiological samples were processed
      using qRT-PCR. Data were analysed by Wilcoxon and Mann-Whitney tests
      (alpha=0.05). RESULTS: There was no significant difference in the microbiota
      present in the primary teeth with and without furcal/periapical lesion.
      Biomechanical preparation was effective in reducing the number of microorganisms
      (P<0.05). The intracanal medications had similar antibacterial activity.
      CONCLUSION: The association of chlorhexidine with calcium hydroxide did not
      increase the antibacterial activity of the intracanal medication in the treatment
      of primary teeth with necrotic pulp with and without furcal/periapical lesion.

PMID- 21883560
TI  - Effect of mode of delivery and feeding practices on acquisition of oral
      Streptococcus mutans in infants.
AB  - OBJECTIVE: It is a well-established fact that colonization of S. mutans occurs
      early in life. The purpose of this study is to determine the correlation between
      mode of delivery and other associating factors with colonization of oral S.
      mutans in the infants. METHODS: The newborns were divided into two groups
      according to the mode of delivery: Infants who were delivered by either caesarean
      section (Group-C) or vaginally (Group-V). A total number of 60 mother-infant
      pairs were included and followed for 1 year. The swab samples were collected for
      the detection of S. mutans. RESULTS: Analysis of data demonstrated the possible
      influence of prolonged bottle feeding (P = 0.007), socioeconomic status (P =
      0.00030) and tasting of food by the mothers (P = 0.0065) on the initial
      acquisition of S. mutans in the oral cavity of infants. CONCLUSION: The causes
      for initial acquisition of oral S. mutans in infants were postnatal factors like
      feeding and oral hygiene practices.

PMID- 21883561
TI  - The role of school-based dental programme on dental caries experience in
      Yogyakarta Province, Indonesia.
AB  - OBJECTIVES: To assess the effectiveness of a school-based dental programme (SBDP)
      in controlling caries by measuring the relationship between the SBDP performance
      and caries experience in children aged 12 in Yogyakarta Province, Indonesia, by
      taking into account influencing factors. METHODS: A cross-sectional survey was
      undertaken of 1906 children participating in SBDPs. Four SBDPs were chosen by
      good and poor performances in urban and rural areas. Caries was assessed using
      WHO criteria whereas behaviour and socio-demographic factors were collected using
      a questionnaire administered to the children. RESULTS: The decayed, missed, and
      filled teeth (DMFT) of children in good SBDPs (2.8 +/- 2.4) was lower than that
      of the counterparts (3.8 +/- 3.4). From path analysis using a structural equation
      model (SEM), place of residence (OR = 4.0) was shown to have a strongest direct
      relationship to caries experience, whereas SBDP performance showed no direct
      relationship. At the same time, SBDP performance was significantly related to
      frequencies of dental visits (OR = 0.3), sugar consumption (OR = 0.8), and tooth
      brushing (OR = 3.2), which in turn are interrelated with place of residence,
      gender, and mother's education. CONCLUSIONS: The study suggests that the
      differences in DMFT of children in good and poor performance SBDPs were caused by
      relation to social factors rather than by relation to oral health service
      activities.

PMID- 21883562
TI  - Knowledge of medical hospital emergency physicians about the first-aid management
      of traumatic tooth avulsion.
AB  - OBJECTIVE: The aim of this study was to evaluate the knowledge of emergency
      medical physicians employed in hospital emergency rooms as to their potential
      role in the treatment for traumatic teeth avulsion injuries (TTAI). METHODS: A 15
      item questionnaire was distributed to the emergency rooms of one university and
      10 public hospitals. The questionnaire gathered data on the respondents'
      professional profiles and self-assessed perceived knowledge and actual knowledge
      of the emergency management of TTAIs. RESULTS: The study was implemented with 69
      emergency physicians present at their workplaces during the time of data
      collection. Of these, 55 (79.7%) were employed at public hospitals and 14 (20.3%)
      at a university hospital. The professional profiles indicated that 47 (68.1%) of
      the participants were general practitioners and the remaining 22 (31.9%) were
      distributed among various other medical specialties. Overall, 28 respondents
      (40.6%) assessed their knowledge regarding medical treatment for TTAI as
      insufficient, and the majority (78.3%) stated that they would like further
      education. Importantly, a large majority of practitioners could not provide
      correct answers to questions related to the emergency management of TTAI.
      CONCLUSION: There is a need to improve the knowledge of emergency medical
      physicians regarding the emergency treatment for TTAI.

PMID- 21883563
TI  - Incurable, invisible and inconclusive: watchful waiting for chronic lymphocytic
      leukaemia and implications for doctor-patient communication.
AB  - Patients with chronic lymphocytic leukaemia (CLL) find it hard to accept a
      diagnosis of an incurable cancer for which no treatment is recommended and which
      may not cause symptoms for many years. We used qualitative interviews with 12
      people with CLL managed by watchful waiting, drawn from a maximum variation
      sample of 39 adults with leukaemia, to explore accounts of watchful waiting and
      implications for clinical management. Patients with CLL recalled being given
      little information about the condition and wanted to know more about how it might
      affect them in the future. The invisibility of CLL meant that some chose not to
      disclose the diagnosis to others. Check-ups sometimes felt cursory, causing
      dissatisfaction. As symptoms increased, lifestyle adaptations became essential,
      well before treatment was warranted. Patients with CLL on watchful waiting
      experience levels of depression, anxiety and quality of life similar to those in
      active treatment; our qualitative approach has illuminated some of the reasons
      for the negative psychological impacts. We relate our findings to perceptions of
      the illness state, doctor-patient communication, and work pressure. We recommend
      that specialists could better support patients by acknowledging psychological
      impacts of CLL, actively listening to patients' concerns, and meeting their needs
      for information.

PMID- 21883564
TI  - Need for psychological follow-up among young adult survivors of childhood cancer.
AB  - Follow-up is recommended for survivors of childhood cancer. Decisions about care
      tend to be made in terms of physical health, but psychological late effects
      including post-traumatic stress disorder (PTSD) and symptoms (PTSS) are
      prevalent. We report prevalence of PTSD/PTSS in a UK cohort, self-care and
      implications for organisation of follow-up. Eligible survivors (n= 218) under
      regular follow-up were invited to complete measures of PTSD, late effects and
      self-efficacy. Information about late effects was also taken from medical notes.
      A total of 118 survivors responded (54.1%) and 108 (49.5%) completed
      questionnaires. Prevalence of clinical PTSD (13.9%) was comparable with US
      findings. Female subjects and those who reported more late effects reported more
      PTSD. In regression analyses, number of survivor-reported late effects (but not
      number-recorded in medical notes) and PTSS predicted self-efficacy. Significant
      numbers of survivors report PTSS but this is unrelated to diagnosis or treatment.
      Female subjects and those who reported more physical late effects also reported
      more PTSS. Decisions to discharge survivors from routine care must consider
      psychological well-being as well as physical late effects. We recommend routine
      psychological screening for all survivors of childhood cancer and suggest this
      can be acceptable to survivors and feasible in clinic.

PMID- 21883565
TI  - Younger and older women's concerns about menopause after breast cancer.
AB  - A number of treatments for breast cancer induce menopause. This study's aim was
      to explore women's perceptions and beliefs about menopausal symptoms and their
      management following breast cancer, and to compare younger and older women's
      experiences. Data were collected via semi-structured focus groups from women who
      had undergone treatment for breast cancer, and who were currently experiencing
      menopausal symptoms. Data were interpreted by way of simple inductive thematic
      analysis. The women experienced a range of menopausal symptoms that they were not
      prepared for and found difficult to manage. The central themes related to their
      lack of knowledge of how to manage menopausal symptoms, and the distress and
      helplessness that arose from this. Women who were diagnosed prior to 40 years of
      age reported additional menopausal issues than women who were older at diagnosis.
      The women in this study expressed a thirst for information related to menopause
      after breast cancer. The women identified that their needs with regard to
      menopause after breast cancer were not being met, either through their own lack
      of knowledge or via conflicting or absent support and management. The importance
      of enabling women to deal with menopausal symptoms was a central theme to emerge
      from the data.

PMID- 21883566
TI  - High risk of urinary tract infections in post-operative gynaecology patients: a
      retrospective case analysis.
AB  - This study was undertaken to determine the incidence and risk factors related to
      the occurrence of urinary tract infections (UTIs), post surgery, in women being
      treated for a gynaecological cancer. A retrospective case analysis of 215 women
      was conducted using data collected via case review with domains covering known
      risk factors for the occurrence of urinary infections. Bacteriuria was defined as
      greater than 10(5) colony-forming units per millilitre. A total of 30.7% of women
      had a UTI post-operatively. Among these, 75.7% infections were Escherichia coli.
      Having a catheter in situ for <=3 days was found to be slightly significant in
      the formation of a UTI post-operatively (U= 3878, P < 0.05). Having a catheter in
      situ for >=7 days was found to be highly significant (chi(2) (1) = 6.602, P <
      0.01), with an odds ratio of 2.44. A positive correlation was found between the
      duration of the catheter in situ and type of UTI (tau= .251, P < 0.01). Although
      urinary catheterisation is known to be related to hospital-acquired infection, a
      shorter duration of catheterisation may reduce the risk of possible infection
      post surgery. Oncology teams need to be more aware of this risk, identify women
      more likely to be catheterised for longer and use preventative strategies for
      managing infection, such as silver nitrite-lined catheters.

PMID- 21883567
TI  - Use of high-dose cisplatin with aprepitant in an outpatient setting.
AB  - Chemotherapy-induced nausea and vomiting (CINV) and nephrotoxicity are adverse
      events induced by cisplatin administration. These effects can be reduced by
      treatment regimens with low-dose cisplatin, but high-dose cisplatin is still
      used. In Japan, high-dose cisplatin is usually administered in an inpatient
      setting to permit management of CINV. However, with use of new-generation
      antiemetic agents such as aprepitant, CINV and nephrotoxicity are controllable in
      an outpatient setting. Here, we discuss issues related to the management of high
      dose cisplatin administration in outpatients. Grade 2 or worse CINV induced by
      high-dose cisplatin occurs in more than 40% of patients without treatment with
      aprepitant, but is controllable by administration of a 5-HT3 receptor antagonist,
      steroids and aprepitant. Moreover, prevention of CINV using these drugs is cost
      effective, since outpatient settings have advantages with regard to health
      economics and patient quality of life. These findings suggest that shifting high
      dose cisplatin administration to the outpatient setting may be achieved with co
      administration of aprepitant. Available facilities and the status of the patient
      should be considered when selecting whether an outpatient setting is suitable for
      administration of cisplatin, but the use of aprepitant and adequate oral
      hydration should allow use of cisplatin in this setting.

PMID- 21883568
TI  - Controlling the cost of breast cancer.
AB  - Breast cancer management is an important part of the health-care system. In the
      current harsh economic climate, these costs have to be controlled, and achieving
      this without compromising quality of care is a daunting challenge. This article
      discusses the need to find effective and well-targeted chemotherapeutic regimens,
      which, when combined with appropriate implementation of novel strategies, will
      provide the optimum treatment for patients while maintaining economic viability.

PMID- 21883569
TI  - Effectiveness of multimedia interactive patient education on knowledge,
      uncertainty and decision-making in patients with end-stage renal disease.
AB  - AIM: This study tested the efficacy of a multimedia interactive DVD as an
      education tool for patients with end-stage renal disease in terms of enhancing
      patient knowledge and decision-making skills and decreasing uncertainty.
      BACKGROUND: End-stage renal case numbers in Taiwan are growing by approximately
      6000 new patients per year. Helping patients choose an optimal treatment method
      to maximise quality of life is an important healthcare issue for this patient
      population. DESIGN: This study adopted a quasi-experimental design and focused on
      subjects being treated at one medical centre in southern Taiwan. The study
      divided subjects into experimental and control groups. METHODS: The experimental
      group received three multimedia interactive DVD nursing-guided interventions. The
      control group received only normal hospital health education. The study gathered
      data using several scales addressing knowledge, uncertainty perception and
      decision regret. Scales were implemented immediately before and after the
      multimedia interactive DVD nursing guidance intervention and at four and eight
      weeks postintervention. This study used an independent t-test, chi-square test
      and repeated measures analysis of variance. RESULTS: This study found significant
      improvements in the experimental group in terms of knowledge, pre-dialysis
      uncertainty and decision regret. Experimental group subjects scored particularly
      less in terms of decision regret than those in the control group. RELEVANCE TO
      CLINICAL PRACTICE: This study demonstrated the efficacy of the developed
      multimedia interactive DVD in significantly improving end-stage renal patient
      knowledge and reducing patient uncertainties and postdecision regret. Study
      findings can be used as a reference guide for clinical nursing education efforts
      in hospital and other healthcare settings.

PMID- 21883571
TI  - The presence of post-traumatic stress disorder symptoms in adolescents three
      months after an 8.0 magnitude earthquake in southwest China.
AB  - AIMS AND OBJECTIVES: The aims of the study were to describe the post-traumatic
      stress disorder symptoms in adolescent survivors three months after Wenchuan 5.12
      Earthquake and to explore its contributing or preventing factors. BACKGROUND:
      Adolescents are more vulnerable to be affected by natural disasters because of
      their special growth stage. Post-traumatic stress disorder symptoms are common
      responses in adolescents after disasters, and its occurrence is related to some
      psychosocial factors. DESIGN: The study used a cross-sectional design in a large
      sample. METHODS: A total of 1976 subjects aged 12-20 were evaluated at three
      months after the earthquake by using the Post-traumatic stress disorder Checklist
      Civilian Version. The Internality, Powerful others and Chance scale and the
      Coping Styles Scale were also administered to the subjects at the same time.
      RESULTS: The mean total score of Post-traumatic Stress Disorder Checklist
      Civilian Chinese Version was 33.64 (SD 11.15; range of score 17-85). The boys
      with a higher level of initial exposure to the earthquake had lower symptoms
      scores than girls with a lower level of initial exposure. Chance locus of control
      and power other locus of control were the powerful risk factors of post-traumatic
      stress disorder symptoms, while the protective factors included withdrawing
      skill, internality locus of control, junior high grade and social supports.
      CONCLUSIONS: Post-traumatic stress disorder symptoms are prevalent psychiatric
      reactions in adolescents after earthquakes. Locus of control and coping strategy
      could play an important role in its occurrence and severity besides demographic
      factors, exposure characteristics and social support factors. RELEVANCE TO
      CLINICAL PRACTICE: This study reveals that adolescents are the vulnerable group
      for suffering psychological stress responses to catastrophic events. Healthcare
      professionals, especially school nurses, should pay more attention to adolescents
      after trauma. Prompt and effective intervention should be carried out to mitigate
      the impact of initial exposure and reduce the occurrence of post-traumatic stress
      disorder symptoms.

PMID- 21883570
TI  - The influence of heart failure on longitudinal changes in cognition among
      individuals 80 years of age and older.
AB  - AIM: The aim of this study was to examine the relationship between heart failure
      and specific cognitive abilities in octogenarians with regard to level and change
      over time. BACKGROUND: Cognitive impairment is influenced by many factors, and
      the impact of heart failure is debated. Intact cognitive ability is crucial for
      successful self-care in patients with heart failure. Middle-aged patients with
      heart failure seem to have an increased risk of cognitive impairment. No studies
      have examined the association between heart failure and longitudinal cognitive
      changes in octogenarians (individuals 80 years and older). DESIGN: A prospective
      longitudinal design. METHODS: Cognitive tests were carried out five times (1991
      2002) in 702 octogenarians from the Swedish Twin Registry, including same-sex
      twin pairs. The test battery included the measurement of processing speed,
      visuospatial ability, short-term, episodic and semantic memory. Latent growth
      curve modelling was employed to measure change and performance over time and
      compares the group diagnosed with heart failure to individuals without a heart
      failure diagnosis. Results.  At baseline, the participants' mean age was 83.5
      years, 67% were women and 13% suffered from heart failure. Individuals diagnosed
      with heart failure scored significantly lower in spatial abilities and episodic
      memory than participants not diagnosed with heart failure. Moreover, measures of
      episodic memory declined more over time in individuals diagnosed with heart
      failure. There were no significant differences between the groups in other
      cognitive tests. CONCLUSION: Spatial problems and episodic memory have
      implications for everyday life. This might contribute to decreased adherence to
      prescribed therapy and self-care management and lead to socio-behavioural
      problems because of an impaired capacity to drive, read and write. RELEVANCE TO
      CLINICAL PRACTICE: Nurses should take into account in their assessment that
      cognitive impairment may restrain elderly heart failure patient's ability to make
      decisions and perform self-care actions. Patient education strategies should also
      be adapted to cognitive ability.

PMID- 21883572
TI  - Fathers of children with disabilities: encounters with health professionals in a
      Chinese context.
AB  - AIMS: The aim of this study was to examine the experiences of fathers of
      developmentally disabled children during interactions with health professionals
      in Taiwan. BACKGROUND: The role of Chinese fathers in raising a disabled child
      has been neglected because most studies on the impact of parenting a child with
      disabilities in this culture have primarily focused on mothers. DESIGN: A
      hermeneutic phenomenological approach was undertaken to recover and interpret
      fathers' experiences. METHOD: Sixteen fathers living with their disabled child (0
      18 years old) were purposively recruited from a teaching hospital in central
      Taiwan. Data were collected using in-depth interviews and journal notes. All
      participants were interviewed twice. Interviews lasted from 50-100 minutes, and
      all were recorded. RESULTS: Three shared meanings were attributed to fathers'
      interactions with health professionals: (1) experiencing no supportive
      communication, (2) missing the critical time for disability management and (3)
      being excluded from medical decision making. CONCLUSIONS: Fathers in Taiwan
      commonly rely on health professionals to solve their child's health problems
      owing to their perceived power to cure and their professional authority in
      Chinese society. However, fathers felt powerless and hopeless when they received
      unclear information and incorrect diagnoses, which delayed appropriate treatment.
      Expressions of dissatisfaction and possessing a sense of futility were common
      experiences related to exclusion in a paternalistic healthcare system. RELEVANCE
      TO CLINICAL PRACTICE: Taiwanese clinicians' attitudes and parental-professional
      relationships challenge an exploration of ethics and standards of medical care
      shaped by Chinese culture. Ways of promoting parental inclusion in decision
      making and care, in particular father's inclusion, need to be explored.
      Recognition of the Chinese mother and father and their differing parental
      healthcare experiences are important to understand to ensure improvement in
      encounters with health professionals and the maximisation of positive health
      outcomes.

PMID- 21883573
TI  - Life is back to normal and yet not - partners' and patient's experiences of life
      of the first year after colorectal cancer surgery.
AB  - AIM: To describe the experience of life the first year after surgery from the
      perspective of persons treated for colorectal cancer and their partners.
      BACKGROUND: Colorectal cancer is a common cancer form, and treatment can cause
      unpleasant side effects such as sexual dysfunction and bowel problems. Partners
      struggle to keep family life normal and provide support. Little is known about
      couples' experiences a year after treatment for colorectal cancer. DESIGN:
      Qualitative descriptive. METHODS: Individual semi-structured interviews with 13
      persons treated for colorectal cancer and their partners, a total of 26
      participants. RESULTS: One theme was identified in the study; 'Life is back to
      normal and yet not': participants described living a normal but different life
      than before. Three subthemes were identified; 'Life has a shadow of death', 'The
      treated body sets the rules' and 'To share or not share the illness'.
      CONCLUSIONS: Findings showed that both the patients' and their partners' lives
      were influenced by uncertainty and the condition of the patient. Attitudes varied
      towards sharing the illness. It was found that information needs varied both
      within and between couples. A future challenge to healthcare personnel is the
      obligation to meet the needs of both patients and their partners on the illness
      trajectory and recovery after treatment for colorectal cancer. RELEVANCE TO
      CLINICAL PRACTICE: Findings enhance the understanding of the impact of colorectal
      cancer on both patients and partners. Healthcare personnel need to assess both
      the patient's and partner's need for information, support and assistance. Support
      groups could be an effective tool for providing information, communication and
      support. Future studies are needed to evaluate such groups.

PMID- 21883574
TI  - A randomised trial on pubertal development and health in China.
AB  - BACKGROUND: Puberty signifies noticeable physical, psychosocial and sexual
      development. It is crucial to help adolescents reach an understanding about
      puberty and related health issues. Considering the sexually conservative culture
      in some areas, to explore appropriate ways to address sexuality and health
      related concerns during puberty is of interest to all stakeholders. AIMS: This
      study aimed to examine the effectiveness of the ecological approach to improve
      adolescents' understanding about puberty and related health risks. DESIGN:
      Modified Solomon four group design. METHODS: Two Grade7 classes were randomly
      selected to form experiment and control group, respectively. A two-hour seminar
      and a brochure about health and development during puberty were provided, and
      some students, parents and instructors in the experimental group commented on the
      intervention. Pre- and post-tests were conducted to measure students' pubertal
      development status and their knowledge, attitudes and behaviours related to
      puberty. RESULTS: Students (n = 228) were aged 13.0 years (SD 0.45). The majority
      was categorised at the stage of mid-puberty or later, and approximately 11.2% of
      116 girls and 22.3% of 112 boys were classified as overweight or obese according
      to body mass index. No significant changes were identified within or between
      groups about knowledge, attitudes and behaviours related to puberty and health
      before and after the intervention. The invention was considered helpful, and an
      enriched delivery was required. CONCLUSIONS: Although the overall feedback was
      positive, this ecological approach to adolescent health and development targeting
      at Grade7 students failed to generate significant effects on students' knowledge,
      attitudes and behaviours surrounding puberty and health. RELEVANCE TO CLINICAL
      PRACTICE: This study reveals that sexuality, particularly romantic relationships
      during puberty, may be perceived negatively in the local society. There is a need
      for school nurses to help all relevant people to understand and respond to
      sexuality-related concerns in a cultural appropriate way.

PMID- 21883575
TI  - School nurses' perspectives on managing mental health problems in children and
      young people.
AB  - AIMS AND OBJECTIVES: To explore the views of school nurses regarding mental
      health problems in young people and their potential for engaging in mental health
      work with this client group. BACKGROUND: Mental health problems in children and
      young people are an important public health issue. Universal children's services
      play a key role in identifying and managing these problems and, while school
      nurses have an important function in this work, little is known about their views
      on this aspect of their role. DESIGN: A qualitative research design employing
      focus group methodology. METHOD: School nurses (n = 33) were purposively sampled
      from four school nursing teams in two English cities for a series of focus
      groups. The focus group data were audio-recorded, transcribed and subsequently
      analysed using 'framework'. RESULTS: Four principal themes emerged from the data.
      In these themes, school nurses were found to value their involvement with the
      mental health of young people, recognising this as an important area of practice.
      Several obstacles to their work in this area were identified: heavy workloads,
      professional rivalries, a lack of confidence and limited education and training
      opportunities. The importance of support from local specialist mental health
      teams was emphasised. CONCLUSIONS: School nurses can be engaged in mental health
      work though, as public health specialists, their role should focus on health
      promotion, assessment, signposting and early intervention activities. To
      facilitate mental health work, school nurses are able to draw on established
      interpersonal skills and supportive networks; however, workload and a lack of
      confidence need to be managed and it is important that they are supported by
      constructive relationships with local specialist mental health teams. RELEVANCE
      TO CLINICAL PRACTICE: This study has implications for nurses and healthcare
      practitioners interested in enhancing the mental health of children and young
      people in school settings.

PMID- 21883576
TI  - Female nurses' sensitivity to male genitalia-related care in mainland China.
AB  - AIMS: To discover the latent psychosocial construct of female nurses' sensitivity
      to male genitalia-related care in the context of sexual conservativeness.
      BACKGROUND: Many nursing activities involve direct exposure or contact with male
      external genitalia. In the sexually conservative culture and the predominance of
      female nurses, this area is the subject of continuing interest and investigation.
      DESIGN: Methodological research design. METHODS: An item pool related to male
      genitalia-related care was generated through a panel of experts and then reduced
      to a short form questionnaire, the Female Nurses' Sensitivity to Male Genitalia
      Related Care scale. Using data from a purposive sample of 588 female nurses, the
      structure of the questionnaire was examined using structural equation modelling.
      The validity was examined against existing scales. RESULTS: The 13-item Female
      Nurses' Sensitivity to Male Genitalia Related Care scale has a two-factor
      structure with high internal consistency (alpha = 0.87) and test-retest
      reliability of 0.90. Nearly all model fit measures reach the criteria of being an
      acceptable model fit except chi-squared statistics. Scores on Female Nurses'
      Sensitivity to Male Genitalia Related Care can be best predicted by that of brief
      Fear of Negative Evaluation Scale, Embarrassability Scale and Situational
      Susceptibility to Embarrassment Scale. CONCLUSIONS: The anxiety of projecting a
      positive image and the pursuit of sexual propriety may underpin female nurses'
      sensitivity to male genitalia-related care. This trait can be measured by the 13
      item female nurses' sensitivity-male genitalia-related care scale with
      satisfactory psychometric properties including internal consistency, reliability,
      content validity and construct validity. RELEVANCE TO CLINICAL PRACTICE:
      Particular attention shall be paid to the negative effects of social rules or
      norms including sexual propriety rules over (female) nurses' perceptions,
      attitudes and behaviours. Strengthening nursing education in this regard is
      important to overcome negative effects on female nurses of male genitalia-related
      care.

PMID- 21883577
TI  - Item response theory: how Mokken scaling can be used in clinical practice.
AB  - AIMS: To demonstrate the principles and application of Mokken scaling.
      BACKGROUND: The history and development of Mokken scaling is described, some
      examples of applications are given, and some recent development of the method are
      summarised. DESIGN: Secondary analysis of data obtained by cross-sectional survey
      methods, including self-report and observation. METHODS: Data from the Edinburgh
      Feeding Evaluation in Dementia scale and the Townsend Functional Ability Scale
      were analysed using the Mokken scaling procedure within the 'R' statistical
      package. Specifically, invariant item ordering (the extent to which the order of
      the items in terms of difficulty was the same for all respondents whatever their
      total scale score) was studied. RESULTS: The Edinburgh Feeding Evaluation in
      Dementia scale and the Townsend Functional Ability Scale showed no violations of
      invariant item ordering, although only the Townsend Functional Ability Scale
      showed a medium accuracy. CONCLUSION: Mokken scaling is an established method for
      item response theory analysis with wide application in the social sciences. It
      provides psychometricians with an additional tool in the development of
      questionnaires and in the study of individuals and their responses to latent
      traits. Specifically, with regard to the analyses conducted in this study, the
      Edinburgh Feeding Evaluation in Dementia scale requires further development and
      study across different levels of severity of dementia and feeding difficulty.
      RELEVANCE TO CLINICAL PRACTICE: Good scales are required for assessment in
      clinical practice and the present paper shows how a relatively recently developed
      method for analysing Mokken scales can contribute to this. The two scales used as
      examples for analysis are highly clinically relevant.

PMID- 21883578
TI  - Kin selection in Columbian ground squirrels: direct and indirect fitness
      benefits.
AB  - Empirical and theoretical studies have supported kin selection by demonstrating
      nepotism or modelling its conditions and consequences. As an alternative, we
      previously found that female Columbian ground squirrels had greater direct
      fitness when more close kin were present. Extending those results, we used
      population matrix methods to calculate minimum estimates of individual fitness,
      estimated direct and indirect components of fitness, estimated inclusive fitness
      by adding the direct fitness (stripped of estimated influences of the social
      environment) and indirect fitness components together, and finally looked for
      inclusive fitness benefits of associations with close kin who seem to be 'genial
      neighbours'. We examined the estimated fitness of a sample of 35 females for
      which complete lifetimes were known for themselves, their mothers and their
      littermate sisters. Six of these females had no cosurviving adult close kin, and
      their direct fitness was significantly lower than 29 females with such kin
      (lambda = 0.66 vs. lambda = 1.23). The net fitness benefit of the presence of
      close kin was thus 0.57. The estimated indirect component of fitness through
      benefits to the direct fitness of close kin was 0.43. Thus, estimated inclusive
      fitness for females with cosurviving close kin (lambda = 1.09) was significantly
      greater than that for females without surviving close kin (viz., lambda = 0.66).
      The presence of closely related and philopatric female kin appeared to result in
      considerable fitness benefits for female ground squirrels, perhaps through the
      behavioural mechanisms of lowered aggression and other forms of behavioural
      cooperation.

PMID- 21883580
TI  - Philopatry and within-colony movements in Columbian ground squirrels.
AB  - Philopatry and dispersal result in selection of habitat locations that may differ
      in resources and social environment and thus should influence fitness components
      like survival and reproduction. We examined short-distance movements of young and
      adult females from natal or previous nesting sites within a colony of Columbian
      ground squirrels (Urocitellus columbianus) in the Rocky Mountains of Alberta,
      Canada, over a 17-year period. Females of all ages were strongly philopatric, yet
      a few (10-15%) exhibited movements that took them to new home ranges. We tested
      three hypotheses to explain the pattern of female natal and breeding movements:
      (1) that movements of philopatric females promote proximity to close kin; (2)
      that range shifts favour close kin via bequeathal of territory and (3) that
      dispersers move to lower density areas where competition for resources is lower.
      Tests of these three hypotheses revealed that: (1) philopatry and movements of
      young and older philopatric females led to proximity to mothers and local
      presence of close kin; (2) breeding dispersal did not result in bequeathal of
      home range to daughters, but movements of philopatric females suggested that they
      shared space with close kin and (3) adult females moved to new ranges with lower
      local densities, though dispersing females also left ranges where local density
      was significantly lower than for philopatric females. Natal and breeding
      movements among years produced two opportunities for territorial females: close
      spatial proximity to close kin via short philopatric movements, and habitats with
      fewer competitors via longer dispersal movements.

PMID- 21883579
TI  - A combined genetic-morphometric analysis unravels the complex biogeographical
      history of Polyommatus icarus and Polyommatus celina common blue butterflies.
AB  - Widespread species have the potential to reveal large-scale biogeographical
      patterns, as well as responses to environmental changes possibly unique to
      habitat generalists. This study presents a continental-scale phylogeographical
      analysis of Polyommatus icarus, one of the most common Palaearctic butterflies,
      and the morphologically and ecologically similar Polyommatus celina, a recently
      discovered cryptic species. By combining data from mitochondrial [cytochrome c
      oxidase subunit I (COI)] and nuclear [internal transcribed spacer (ITS2)]
      molecular markers with geometric morphometrics, we document a complex
      phylogeographical history for the two species. Despite morphological
      similarities, the genetic divergence between these two species is high (more than
      5% at COI) and they are not sister species. For the first time, we show that P.
      celina occurs not only in North Africa but also in Europe, where it inhabits
      several west Mediterranean islands, as well as large parts of Iberia, where it
      occurs in parapatry with P. icarus. The two species appear to completely exclude
      each other on islands, but we provide morphological and molecular evidence that
      introgression occurred in the Iberian Peninsula. We discovered strongly diverged
      lineages that seem to represent relict populations produced by past range
      expansions and contractions: Crete and Iberian isolates for P. icarus, Balearics
      Sardinia and Sicily-Lipari for P. celina. This study shows that a combined
      genetic-morphometric approach can shed light on cryptic diversity while providing
      the necessary resolution to reconstruct a fine-scale phylogeographical history of
      species at both spatial and temporal levels.

PMID- 21883581
TI  - Back from the brink: potential for genetic rescue in a critically endangered
      tree.
AB  - Rare plant species are vulnerable to genetic erosion and inbreeding associated
      with small population size and isolation due to increasing habitat fragmentation.
      The degree to which these problems undermine population viability remains
      debated. We explore genetic and reproductive processes in the critically
      endangered long-lived tropical tree Medusagyne oppositifolia, an endemic to the
      Seychelles with a naturally patchy distribution. This species is failing to
      recruit in three of its four populations. We evaluate whether recruitment failure
      is linked to genetic problems associated with fragmentation, and if genetic
      rescue can mitigate such problems. Medusagyne oppositifolia comprises 90 extant
      trees in four populations, with only the largest (78 trees) having successful
      recruitment. Using 10 microsatellite loci, we demonstrated that genetic diversity
      is high (H(E) : 0.48-0.63; H(O) : 0.56-0.78) in three populations, with only the
      smallest population having relatively low diversity (H(E) : 0.26 and H(O) :
      0.30). All populations have unique alleles, high genetic differentiation, and
      significant within population structure. Pollen and seed dispersal distances were
      mostly less than 100 m. Individuals in small populations were more related than
      individuals in the large population, thus inbreeding might explain recruitment
      failure in small populations. Indeed, inter-population pollination crosses from
      the large donor population to a small recipient population resulted in higher
      reproductive success relative to within-population crosses. Our study highlights
      the importance of maintaining gene flow between populations even in species that
      have naturally patchy distributions. We demonstrate the potential for genetic and
      ecological rescue to support conservation of plant species with limited gene
      flow.

PMID- 21883582
TI  - The evolution of social philopatry and dispersal in female mammals.
AB  - In most social mammals, some females disperse from their natal group while others
      remain and breed there throughout their lives but, in a few, females typically
      disperse after adolescence and few individuals remain and breed in their natal
      group. These contrasts in philopatry and dispersal have an important consequence
      on the kinship structure of groups which, in turn, affects forms of social
      relationships between females. As yet, there is still widespread disagreement
      over the reasons for the evolution of habitual female dispersal, partly as a
      result of contrasting definitions of dispersal. This paper reviews variation in
      the frequency with which females leave their natal group or range (social
      dispersal) and argues that both the avoidance of local competition for resources
      and breeding opportunities and the need to find unrelated partners play an
      important role in contrasts between and within species.

PMID- 21883583
TI  - Causes and consequences of living in closed societies: lessons from a long-term
      socio-genetic study on Bechstein's bats.
AB  - Understanding the ecological, behavioural and genetic factors influencing animal
      social systems is crucial to investigating the evolution of sociality. Despite
      the recent advances in population genetic methods and the analysis of social
      interactions, long-term studies exploring the causes and consequences of social
      systems in wild mammals are rare. Here, we provide a synthesis of 15 years of
      data on the Bechstein's bat (Myotis bechsteinii), a species that raises its young
      in closed societies of 10-45 females living together for their entire lives and
      where immigration is virtually absent. We discuss the potential causes and
      consequences of living in closed societies, based on the available data on
      Bechstein's bat and other species with similar social systems. Using a
      combination of observational and genetic data on the bats together with genetic
      data on an ecto-parasite, we suggest that closed societies in Bechstein's bats
      are likely caused by a combination of benefits from cooperation with familiar
      colony members and parasite pressure. Consequences of this peculiar social system
      include increased sensitivity to demographic fluctuations and limits to dispersal
      during colony foundation, which have broad implications for conservation. We also
      hope to illustrate by synthesizing the results of this long-term study the
      diversity of tools that can be applied to hypothesize about the factors
      influencing a species' social system. We are convinced that with the expansion of
      the number of social mammals for which comparably detailed socio-genetic long
      term data are available, future comparative studies will provide deeper insights
      into the evolution of closed societies.

PMID- 21883584
TI  - Mechanisms of kin discrimination inferred from pedigrees and the spatial
      distribution of mates.
AB  - Where animals avoid inbreeding, different mechanisms of kin discrimination can
      leave different 'signatures' in the patterns of observed mate relationship. For
      example, consider a species with no paternal care. If a female avoids mating with
      familiar individuals, one would expect a deficit of offspring whose parents are
      maternal half-siblings, but paternal half-siblings would be unfamiliar with each
      other and thus have offspring at the frequency expected by chance. If spatial
      cues are used to avoid inbreeding, a female would be expected to produce few
      offspring with males (even unrelated males) living near her birth site. We
      searched for these and other signatures with data from a long-term study of
      banner-tailed kangaroo rats, Dipodomys spectabilis, in Arizona, USA, using a
      combination of intensive censusing, mapping of available dens, microsatellite
      based parentage determination, and a randomization routine that determines the
      numbers of offspring expected if females in the population mate indiscriminately
      among the males available to them. The data are consistent with the hypothesis
      that kangaroo rats discriminate kin by familiarity developed via association
      early in life, rather than by using spatial cues or self-referential phenotype
      matching. Our approach should be widely applicable as a means of assessing the
      degree to which kin discrimination exists (in contexts like nepotism as well as
      inbreeding avoidance) and in inferring what cues animals use to assess categories
      of relationship.

PMID- 21883585
TI  - A fuzzy-set-theory-based approach to analyse species membership in DNA barcoding.
AB  - Reliable assignment of an unknown query sequence to its correct species remains a
      methodological problem for the growing field of DNA barcoding. While great
      advances have been achieved recently, species identification from barcodes can
      still be unreliable if the relevant biodiversity has been insufficiently sampled.
      We here propose a new notion of species membership for DNA barcoding-fuzzy
      membership, based on fuzzy set theory-and illustrate its successful application
      to four real data sets (bats, fishes, butterflies and flies) with more than 5000
      random simulations. Two of the data sets comprise especially dense
      species/population-level samples. In comparison with current DNA barcoding
      methods, the newly proposed minimum distance (MD) plus fuzzy set approach, and
      another computationally simple method, 'best close match', outperform two
      computationally sophisticated Bayesian and BootstrapNJ methods. The new method
      proposed here has great power in reducing false-positive species identification
      compared with other methods when conspecifics of the query are absent from the
      reference database.

PMID- 21883586
TI  - Microgeographic socio-genetic structure of an African cooperative breeding
      passerine revealed: integrating behavioural and genetic data.
AB  - Dispersal can be motivated by multiple factors including sociality. Dispersal
      behaviour affects population genetic structure that in turn reinforces social
      organization. We combined observational information with individual-based genetic
      data in the Karoo scrub-robin, a facultative cooperatively breeding bird, to
      understand how social bonds within familial groups affect mating patterns, cause
      sex asymmetry in dispersal behaviour and ultimately influence the evolution of
      dispersal. Our results revealed that males and females do not have symmetrical
      roles in structuring the population. Males are extremely philopatric and tend to
      delay dispersal until they gain a breeding position within a radius of two
      territories around the natal site. By contrast, females dispersed over larger
      distances, as soon as they reach independence. This resulted in male
      neighbourhoods characterized by high genetic relatedness. The long-distance
      dispersal strategy of females ensured that Karoo scrub-robins do not pair with
      relatives thereby compensating for male philopatry caused by cooperation. The
      observed female-biased strategy seems to be the most prominent mechanism to
      reduce the risk of inbreeding that characterizes social breeding system. This
      study demonstrates that tying together ecological data, such as breeding status,
      determining social relationships with genetic data, such as kinship, provides
      valuable insights into the proximate causes of dispersal, which are central to
      any evolutionary interpretation.

PMID- 21883587
TI  - ABGD, Automatic Barcode Gap Discovery for primary species delimitation.
AB  - Within uncharacterized groups, DNA barcodes, short DNA sequences that are present
      in a wide range of species, can be used to assign organisms into species. We
      propose an automatic procedure that sorts the sequences into hypothetical species
      based on the barcode gap, which can be observed whenever the divergence among
      organisms belonging to the same species is smaller than divergence among
      organisms from different species. We use a range of prior intraspecific
      divergence to infer from the data a model-based one-sided confidence limit for
      intraspecific divergence. The method, called Automatic Barcode Gap Discovery
      (ABGD), then detects the barcode gap as the first significant gap beyond this
      limit and uses it to partition the data. Inference of the limit and gap detection
      are then recursively applied to previously obtained groups to get finer
      partitions until there is no further partitioning. Using six published data sets
      of metazoans, we show that ABGD is computationally efficient and performs well
      for standard prior maximum intraspecific divergences (a few per cent of
      divergence for the five data sets), except for one data set where less than three
      sequences per species were sampled. We further explore the theoretical
      limitations of ABGD through simulation of explicit speciation and population
      genetics scenarios. Our results emphasize in particular the sensitivity of the
      method to the presence of recent speciation events, via (unrealistically) high
      rates of speciation or large numbers of species. In conclusion, ABGD is fast,
      simple method to split a sequence alignment data set into candidate species that
      should be complemented with other evidence in an integrative taxonomic approach.

PMID- 21883588
TI  - Climate effects on life cycle variation and population genetic architecture of
      the black bean aphid, Aphis fabae.
AB  - Aphid species may exhibit different reproductive modes ranging from cyclical to
      obligate parthenogenesis. The distribution of life cycle variation in aphids is
      generally determined by ecological forces, mainly climate, because only sexually
      produced diapausing eggs can survive harsh winters or periods of absence of
      suitable host plants. Aphids are thus interesting models to investigate intrinsic
      and environmental factors shaping the competition among sexual and asexual
      lineages. We conducted a Europe-wide sampling of black bean aphids, Aphis fabae,
      and combined population genetic analyses based on microsatellite data with an
      experimental determination of life cycle strategies. Aphids were collected from
      broad beans (Vicia faba) as well as some Chenopodiaceae, but we detected no
      genetic differentiation between aphids from different host plants. Consistent
      with model predictions, life cycle variation was related to climate, with aphids
      from areas with cold winters investing more in sexual reproduction than aphids
      from areas with mild winters. Accordingly, only populations from mild areas
      exhibited a clear genetic signature of clonal reproduction. These differences
      arise despite substantial gene flow over large distances, which was evident from
      a very low geographic population structure and a lack of isolation-by-distance
      among 18 sites across distances of more than 1000 km. There was virtually no
      genetic differentiation between aphids with different reproductive modes,
      suggesting that new asexual lineages are formed continuously. Indeed, a
      surprising number of A. fabae genotypes even from colder climates produced some
      parthenogenetic offspring under simulated winter conditions. From this we predict
      that a shift to predominantly asexual reproduction could take place rapidly under
      climate warming.

PMID- 21883589
TI  - Using a genetic network to parameterize a landscape resistance surface for
      fishers, Martes pennanti.
AB  - Knowledge of dispersal-related gene flow is important for addressing many basic
      and applied questions in ecology and evolution. We used landscape genetics to
      understand the recovery of a recently expanded population of fishers (Martes
      pennanti) in Ontario, Canada. An important focus of landscape genetics is
      modelling the effects of landscape features on gene flow. Most often resistance
      surfaces in landscape genetic studies are built a priori based upon nongenetic
      field data or expert opinion. The resistance surface that best fits genetic data
      is then selected and interpreted. Given inherent biases in using expert opinion
      or movement data to model gene flow, we sought an alternative approach. We used
      estimates of conditional genetic distance derived from a network of genetic
      connectivity to parameterize landscape resistance and build a final resistance
      surface based upon information-theoretic model selection and multi-model
      averaging. We sampled 657 fishers from 31 landscapes, genotyped them at 16
      microsatellite loci, and modelled the effects of snow depth, road density, river
      density, and coniferous forest on gene flow. Our final model suggested that road
      density, river density, and snow depth impeded gene flow during the fisher
      population expansion demonstrating that both human impacts and seasonal habitat
      variation affect gene flow for fishers. Our approach to building landscape
      genetic resistance surfaces mitigates many of the problems and caveats associated
      with using either nongenetic field data or expert opinion to derive resistance
      surfaces.

PMID- 21883590
TI  - Expression of olfactory receptors in different life stages and life histories of
      wild Atlantic salmon (Salmo salar).
AB  - It has been hypothesized that salmonids use olfactory cues to return to their
      natal rivers and streams. However, the key components of the molecular pathway
      involved in imprinting and homing are still unknown. If odorants are involved in
      salmon homing migration, then olfactory receptors should play a critical role in
      the dissipation of information from the environment to the fish. Therefore, we
      examined the expression profiles of a suite of genes encoding olfactory receptors
      and other olfactory-related genes in the olfactory rosettes of different life
      stages in two anadromous and one non-anadromous wild Atlantic salmon populations
      from Newfoundland, Canada. We identified seven differentially expressed OlfC
      genes in juvenile anadromous salmon compared to returning adults in both
      populations of anadromous Atlantic salmon. The salmon from the Campbellton River
      had an additional 10 genes that were differentially expressed in juveniles
      compared to returning adults. There was no statistically significant difference
      in gene expression of any of the genes in the non-anadromous population (P <
      0.01). The function of the OlfC gene products is not clear, but they are
      predicted to be amino acid receptors. Other studies have suggested that salmon
      use amino acids for imprinting and homing. This study, the first to examine the
      expression of olfactory-related genes in wild North American Atlantic salmon, has
      identified seven OlfC genes that may be involved in the imprinting and homeward
      migration of anadromous Atlantic salmon.

PMID- 21883591
TI  - Social flexibility and social evolution in mammals: a case study of the African
      striped mouse (Rhabdomys pumilio).
AB  - Environmental change poses challenges to many organisms. The resilience of a
      species to such change depends on its ability to respond adaptively. Social
      flexibility is such an adaptive response, whereby individuals of both sexes
      change their reproductive tactics facultatively in response to fluctuating
      environmental conditions, leading to changes in the social system. Social
      flexibility focuses on individual flexibility, and provides a unique opportunity
      to study both the ultimate and proximate causes of sociality by comparing between
      solitary and group-living individuals of the same population: why do animals form
      groups and how is group-living regulated by the environment and the neuro
      endocrine system? These key questions have been studied for the past ten years in
      the striped mouse Rhabdomys pumilio. High population density favours philopatry
      and group-living, while reproductive competition favours dispersal and solitary
      living. Studies of genetic parentage reveal that relative fitness of alternative
      reproductive tactics depends on the prevailing environment. Tactics have
      different fitness under constrained ecological conditions, when competitive
      ability is important. Under conditions with relaxed ecological constraints,
      alternative tactics can yield equal fitness. Both male and female striped mice
      display alternative reproductive tactics based on a single strategy, i.e. all
      individuals follow the same decision rules. These changes are regulated by
      endocrine mechanisms. Social flexibility is regarded as an adaptation to
      unpredictably changing environments, selecting for high phenotypic flexibility
      based on a broad reaction norm, not on genetic polymorphism for specific tactics.

PMID- 21883592
TI  - High-amplitude theta wave bursts during REM sleep and cataplexy in hypocretin
      deficient narcoleptic mice.
AB  - Neurons that release hypocretin (HCRT; orexin) peptides control wake-sleep states
      and autonomic functions, and are lost in patients with narcolepsy with cataplexy.
      Bursts of high-amplitude electroencephalographic (EEG) activity have been
      reported during behavioural arrests and rapid eye movement sleep (REMS) episodes
      at sleep onset in HCRT-deficient narcoleptic mice. Quantitative information on
      these EEG phenomena is lacking. We aimed to quantify EEG frequency, occurrence
      rate, daily rhythm and cardiovascular correlates of high-amplitude EEG bursts
      during REMS and cataplexy. Twenty HCRT-deficient mice and 15 congenic wild-type
      controls were instrumented with electrodes for sleep recordings and a telemetric
      blood pressure transducer. Short (1-2 s) high-amplitude bursts of pointed theta
      waves (7 Hz) occurred during either REMS or cataplexy in 80% of HCRT-deficient
      mice without any significant accompanying modification in systolic blood pressure
      or heart period. Theta bursts were significantly more likely to occur during the
      dark period and in the last third of REMS episodes. Similar EEG events were
      detected in a significantly lower fraction (27%) of wild-type mice and with a
      significantly lower occurrence rate (0.8 versus 5 per hour of REMS). These data
      demonstrate that occurrence of high-amplitude theta bursts is facilitated during
      REMS and cataplexy in narcoleptic mice. Analysis of EEG frequency and daily and
      intra-episode patterns of event occurrence do not support interpretation of theta
      bursts as temporally displaced pre-REMS spindles. Facilitation of high-amplitude
      theta bursts may thus represent a novel neurophysiological abnormality associated
      with chronic HCRT deficiency.

PMID- 21883593
TI  - Acute intermittent hypoxia induces phrenic long-term facilitation which is
      modulated by 5-HT1A receptor in the caudal raphe region of the rat.
AB  - Obstructive sleep apnoea (OSA) is characterized by periods of upper airway
      collapse accompanied by repeated episodes of hypoxia. In experimental animals
      repeated bouts of hypoxia may evoke sustained augmentation of phrenic nerve
      activity, known as phrenic long-term facilitation (pLTF). This form of
      physiological compensation might contribute to stable breathing, minimizing the
      occurrence of apnoeas and/or hypopnoeas during sleep in patients with OSA.
      Serotonin (5-HT) has been shown to modulate respiratory neuronal activity,
      possibly via projections originating in the raphe nuclei. Our model focuses on
      the effects of 5-HT1A receptors blockade by selective antagonist WAY-100635 into
      the caudal raphe region on phrenic long-term facilitation after exposure to acute
      intermittent hypoxia (AIH) episodes. Adult, male, urethane-anaesthetized,
      vagotomized, paralyzed and mechanically ventilated Sprague-Dawley rats were
      exposed to AIH protocol. Experimental group received microinjection of WAY-100635
      into the caudal raphe nucleus, whereas the control group received saline into the
      same site. Peak phrenic nerve activity and respiratory rhythm parameters were
      analysed during five hypoxic episodes, as well as at 15, 30 and 60 min after the
      end of hypoxias. In the control group, 1 h post-hypoxia pLTF was developed.
      Microinjections of selective 5-HT1A receptor antagonist WAY-100635 into the raphe
      nuclei prior to the AIH protocol prevented induction of pLTF. These results
      suggest that 5-HT1A receptor activation at supraspinal level is important for
      induction of pLTF, which is suggested to be an important respiratory
      neuroplasticity model in animal studies that possibly correlates with OSA in
      humans.

PMID- 21883594
TI  - Reversal of handedness effects on bimanual coordination in adults with Down
      syndrome.
AB  - BACKGROUND: Research on unimanual tasks suggested that motor asymmetries between
      hands may be reduced in people with Down syndrome. Our study examined handedness
      (as assessed by hand performance) and perceptual-motor integration effects on
      bimanual coordination. METHODS: Adults with Down syndrome (13 non-right-handed,
      22 right-handed), along with comparison groups of adults (16 non-right-handed, 21
      right-handed) and children (15 non-right-handed, 22 right-handed) without Down
      syndrome, drummed with auditory, verbal and visual instructions. RESULTS: In
      contrast to handedness effects in the children and adults without Down syndrome,
      right-handed participants with Down syndrome led more with the left hand, and had
      lower coordination stability than non-right-handed participants with Down
      syndrome. CONCLUSIONS: The reversed handedness effect during bimanual
      coordination suggests a complex relationship between handedness and task
      requirements in adults with Down syndrome.

PMID- 21883595
TI  - Family quality of life of Australian families with a member with an
      intellectual/developmental disability.
AB  - BACKGROUND: Family quality of life (FQOL) is a recent concept in
      intellectual/developmental disability research. Outcomes for the family are
      important to the provision of services because families, rather than
      institutions, are increasingly considered the primary support unit. This article
      presents Australian findings using the international Family Quality of Life
      Survey: Main Caregivers of People with Intellectual or Developmental Disabilities
      (FQOLS-2006). METHOD: Forty-two South Australian main caregivers of people with
      an intellectual/developmental disability were interviewed using the FQOLS-2006.
      The FQOL domains assessed were Health of the Family, Financial Well-being, Family
      Relationships, Support from Other People, Support from Disability-Related
      Services, Influence of Values, Careers, Leisure and Recreation, and Community
      Interaction. Domains were measured in terms of Importance, Opportunities,
      Attainment, Initiative, Stability and Satisfaction. The FQOLS-2006 asked about
      the family's practical and emotional Support from Other People together, whereas
      the current study separated the constructs of practical and emotional support.
      Questions pertaining to FQOL in the past were also added, in order to gain a
      broader picture of present FQOL. RESULTS: Results indicated that families
      considered all the FQOL domains to be important. However, Health, Family
      Relationships and Financial Well-being were regarded as slightly more important
      than Practical and Emotional Support from Others. The attainment of Family
      Relationships, Health, Values, and Leisure and Recreation were rated as quite a
      bit, but Practical Support from Other People was only rated as a little. Families
      were generally satisfied with all FQOL domains, but they were satisfied with
      their Family Relationships and they were neither satisfied or dissatisfied with
      their Financial Well-being. Results also indicated that there was a need to
      distinguish between the provision of practical and emotional support from others,
      because the attainment of emotional support was rated at a slightly higher level
      than practical support. CONCLUSIONS: The FQOLS-2006 provided a comprehensive
      measure of FQOL, which, with some additional modifications, could be used to
      better inform service provisions and ultimately enhance the quality of life of
      people with intellectual/developmental disabilities and their families.

PMID- 21883596
TI  - The quantitative measurement of family quality of life: a review of available
      instruments.
AB  - BACKGROUND: Family quality of life (FQOL) has emerged as an important outcome of
      service delivery for individuals with disabilities and their families. The
      purpose of this review was to explore the disparity of scale development
      approaches between families with children with disabilities and families from
      other populations and identify strengths to serve as a source of recommendations
      to improve the measurements of FQOL in the disability field. METHOD: We conducted
      a keyword search of 25 databases. Sixteen measurement tools on FQOL, family well
      being and family satisfaction currently used in the disability field, healthcare
      field and general family studies published in journals from 1980 to 2009 were
      included in the analysis. RESULTS: Three themes emerged from the detailed
      analysis and comparisons of the instruments: (1) description of the primary
      purpose and theoretical basis; (2) identification of the tool's respondents,
      domains, response formats and scoring strategies to assess family systems; and
      (3) summarisation of available psychometric information. CONCLUSIONS: As family
      researchers continue their mission to conceptualise and theorise about FQOL, they
      should also promote the refinement of FQOL measurements and consider the
      implications from family instruments used in the healthcare and general family
      fields from the following aspects: (1) domains of FQOL; (2) units of analysis;
      (3) response format; (4) scoring choice; and (5) psychometric evaluation.

PMID- 21883597
TI  - Relationship between individual quality of life and family quality of life for
      people with intellectual disability living in Italy.
AB  - BACKGROUND: There is substantial literature investigating quality of life (QoL)
      of individuals with intellectual disability (ID). QoL of families of people with
      ID is emerging as an important field of research. Despite this, there is a lack
      of studies regarding their relationship. AIM: The present paper aimed to study
      the relationship between QoL scores of individuals with ID and members of their
      families. METHODS: Twenty-seven parents or relatives of 27 adults with ID were
      recruited by four different research centres across Tuscany (Italy) to be
      interviewed through the Italian adaptation of the Family Quality of Life Survey -
      2006 (FQoLS-2006), a tool developed for use in a multiple-country study on family
      QoL. The FQoLS-2006 was translated and adapted to Italian through three
      revisions. The last was submitted to the authors of the original version, who
      also maintain an electronic data file and data archive for statistical
      evaluations in various countries. QoL of persons with ID was assessed through the
      administration of the Quality of Life - Instrument Package. QoL scores were
      analysed to describe population characteristics and to examine the relationships
      among measures of individual and family QoL using correlations (Pearson and
      Spearman). RESULTS: Findings showed that family ratings of QoL were generally
      low. Families interviewed reported a low level of QoL in 'Support from Others'
      and 'Community Interaction', while 'Family Relationships' and 'Health of the
      Family' rated higher. For individual QoL, individuals had the lowest scores in
      the area of 'Spiritual being' and higher scores in the area of 'Physical being'.
      Correlations examining possible relationships among Importance, Satisfaction and
      Opportunities found some statistically significant correlation coefficients
      between some aspects of the three main areas of individual QoL (Being, Belonging
      and Becoming) and the nine family domains. Most of these correlations regarded
      family 'Financial Well-Being', 'Family Relationships, 'Support from Service' and
      'Support from Others' areas. CONCLUSIONS: The results of this study suggest that
      QoL is perceived somewhat differently by individuals with ID and by members of
      their families. This difference could negatively impact QoL of people with ID, if
      their views are not taken into account when planning for family support. The
      relationships between individual and family QoL appear to be quite complex, and
      such complexity needs to be clarified in future research.

PMID- 21883598
TI  - Autism spectrum disorder in Down syndrome: cluster analysis of Aberrant Behaviour
      Checklist data supports diagnosis.
AB  - BACKGROUND: The diagnostic validity of autism spectrum disorder (ASD) based on
      Diagnostic and Statistical Manual of Mental Disorders (DSM) has been challenged
      in Down syndrome (DS), because of the high prevalence of cognitive impairments in
      this population. Therefore, we attempted to validate DSM-based diagnoses via an
      unbiased categorisation of participants with a DSM-independent behavioural
      instrument. METHODS: Based on scores on the Aberrant Behaviour Checklist -
      Community, we performed sequential factor (four DS-relevant factors: Autism-Like
      Behaviour, Disruptive Behaviour, Hyperactivity, Self-Injury) and cluster analyses
      on a 293-participant paediatric DS clinic cohort. The four resulting clusters
      were compared with DSM-delineated groups: DS + ASD, DS + None (no DSM diagnosis),
      DS + DBD (disruptive behaviour disorder) and DS + SMD (stereotypic movement
      disorder), the latter two as comparison groups. RESULTS: Two clusters were
      identified with DS + ASD: Cluster 1 (35.1%) with higher disruptive behaviour and
      Cluster 4 (48.2%) with more severe autistic behaviour and higher percentage of
      late onset ASD. The majority of participants in DS + None (71.9%) and DS + DBD
      (87.5%) were classified into Cluster 2 and 3, respectively, while participants in
      DS + SMD were relatively evenly distributed throughout the four clusters.
      CONCLUSIONS: Our unbiased, DSM-independent analyses, using a rating scale
      specifically designed for individuals with severe intellectual disability,
      demonstrated that DSM-based criteria of ASD are applicable to DS individuals
      despite their cognitive impairments. Two DS + ASD clusters were identified and
      supported the existence of at least two subtypes of ASD in DS, which deserve
      further characterisation. Despite the prominence of stereotypic behaviour in DS,
      the SMD diagnosis was not identified by cluster analysis, suggesting that high
      level stereotypy is distributed throughout DS. Further supporting DSM diagnoses,
      typically behaving DS participants were easily distinguished as a group from
      those with maladaptive behaviours.

PMID- 21883599
TI  - Ethnic factors in mental health service utilisation among people with
      intellectual disability in high-income countries: systematic review.
AB  - BACKGROUND: An emerging literature suggests that ethnic and cultural factors
      influence service utilisation among people with intellectual disability (ID), but
      this has not previously been reviewed. AIMS: To investigate possible ethnic
      variation in uptake of mental health services in children, adolescents and adults
      with ID in high-income countries. METHOD: A systematic review using main
      databases of studies that consider ethnic influences on mental health utilisation
      of people with ID. Methodological quality of studies was assessed. RESULTS: Nine
      studies that reached selection criteria were identified. Six studies that
      compared two or more ethnic groups found a variation in levels of mental health
      service utilisation. The most consistent finding was that South Asian children,
      adolescents and adults with ID in the UK had lower use of mental health services
      than White British comparison groups. CONCLUSION: Ethnic influences on mental
      health service utilisation were identified. Understanding their significance and
      potential negative consequences requires further investigation.

PMID- 21883600
TI  - The overweight: obesity and plasma lipids in adults with intellectual disability
      and mental illness.
AB  - BACKGROUND: Previous studies in adults with intellectual disabilities (ID) have
      reported a higher prevalence of obesity than in the general population, and a
      trend to an increase in the prevalence of excess weight. However, little
      information is available on body weight status and lipids levels of adults with
      ID and co-existing mental illness. The aim of this study was to address this
      information gap, by conducting a stepwise multiple regression analysis to predict
      BMI, thereby allowing the investigation of (semi-)partial correlations, which
      assess the extent to which a particular predictor variable is associated with BMI
      over and above the other predictors. METHODS: A study of the patients with ID and
      psychiatric illness registered in the service. Collected data included body mass
      index (BMI), age, gender, the presence of additional physical conditions,
      residential status, mental illness and use the psychotropic medication. We
      analysed the lipid profile including serum cholesterol together with low-density
      lipoprotein, high-density lipoprotein (HDL), triglycerides and the serum
      cholesterol/HDL ratio. Data for these variables were entered into a stepwise
      multiple linear regression to predict BMI. RESULTS: 28% of the participants were
      overweight and 41% obese. Most of the obese patients were men with mild ID (P =
      0.039). Level of ID (P = 0.003), gender (P = 0.001) and serum triglycerides (P =
      0.026) had significant predictive value in the regression model. There were no
      significant differences in either the mean serum cholesterol levels or the mean
      triglyceride levels between those taking and those not taking first-generation
      antipsychotics, second-generation antipsychotics or anti-epileptic medication.
      CONCLUSIONS: The rate of obesity in our sample was higher than in previous
      studies. The most predictive combination of predictors to predict BMI was ID
      level, gender and serum triglyceride levels. Serum triglyceride and cholesterol
      levels did not appear to be unduly affected by first- or second-generation
      antipsychotic medication or by antiepileptic medication.

PMID- 21883601
TI  - Social skills and associated psychopathology in children with chromosome 22q11.2
      deletion syndrome: implications for interventions.
AB  - BACKGROUND: Although distinctive neuropsychological impairments have been
      delineated in children with chromosome 22q11 deletion syndrome (22q11DS), social
      skills and social cognition remain less well-characterised. OBJECTIVE: To examine
      social skills and social cognition and their relationship with neuropsychological
      function/behaviour and psychiatric diagnoses in children with 22q11DS. METHODS:
      Sixty-six children with 22q11DS and 54 control participants underwent
      neuropsychological testing and were administered the Diagnostic Analysis of Non
      Verbal Accuracy (DANVA) for face and auditory emotion recognition, a measure of
      social cognition: their parents/guardians were administered the Social Skills
      Rating System (SSRS) - parent version, Child Behavior Checklist (CBCL) - parent
      version and the Computerised Diagnostic Interview Schedule for Children (C-DISC).
      RESULTS: The 22q11DS group exhibited significantly lower social skills total
      score and more problem social behaviours, lower neurocognitive functioning,
      higher rates of anxiety disorders and more internalising symptoms than the
      control group. Participants with 22q11DS also exhibited significant deficits in
      their ability to read facial expressions compared with the control group, but
      performed no differently than the control participants in the processing of
      emotions by tone of voice. Within the 22q11DS group, higher social competency was
      correlated with higher global assessment of functioning and parental socio
      economic status. Social competency was worse in those with anxiety disorders,
      attention deficit hyperactivity disorder, more than two psychiatric diagnoses on
      the C-DISC and higher internalising symptoms. No significant correlations of SSRS
      scores were seen with IQ, executive functions, attention, or verbal learning and
      memory. No correlations were found between social cognition and social skill
      scores. CONCLUSION: Our results indicate that social skills in children with
      22q11DS are associated with behaviour/emotional functioning and not with
      neurocognition. Thus, treating the behaviour or emotional problems such as
      attention deficit hyperactivity disorder and anxiety disorders may provide a
      pathway for improving social skills in these children.

PMID- 21883602
TI  - Cost-effectiveness of tobacco control policies in Vietnam: the case of personal
      smoking cessation support.
AB  - AIMS: To examine the cost-effectiveness of personal smoking cessation support in
      Vietnam. DESIGN, SETTING AND PARTICIPANTS: We followed-up the population aged 15
      years and over in 2006 to model the costs and health gains associated with five
      interventions: physician brief advice; nicotine replacement therapy (patch and
      gum); bupropion; and varenicline. Threshold analysis was undertaken to determine
      the price levels of pharmaceuticals for the interventions to be cost-effective. A
      multi-state life table model was constructed such that the interventions affect
      the smoking cessation behaviour of the age cohorts, and the resulting smoking
      prevalence defines their health outcomes. A health-care perspective was employed.
      MEASUREMENTS: Cost-effectiveness is measured in 2006 Vietnamese Dong (VND) per
      disability-adjusted life year (DALY) averted. We adopted the World Health
      Organization thresholds of being 'cost-effective' if less than three times gross
      domestic product (GDP) per capita (VND 34,600,000) and 'very cost-effective' if
      less than GDP per capita (VND 11,500,000). FINDINGS: The cost-effectiveness
      result of physician brief advice was VND 1,742,000 per DALY averted
      (international dollars 543), which was 'very cost-effective'. Varenicline
      dominated bupropion and nicotine-replacement therapies, although it did not fall
      within the range of being 'cost-effective' under different scenarios. The
      threshold analysis revealed that prices of pharmaceuticals must be substantially
      lower than the levels from other countries if pharmacological therapies are to be
      cost-effective in Vietnam. CONCLUSIONS: Physician brief advice is a cost
      effective intervention and should be included in the priority list of tobacco
      control policy in Vietnam. Pharmacological therapies are not cost-effective, and
      so they are not recommended in Vietnam at this time unless pharmaceuticals could
      be produced locally at substantially lower costs in the future.

PMID- 21883603
TI  - The effect of methadone on emotional reactivity.
AB  - AIMS: Opioids have been implicated in emotion regulation. Opioid users report
      decreased negative emotional response, but there has been no formal study on the
      effect of opioid administration on emotional reactivity. The aim of this study
      was to investigate the effect of methadone on emotional reactivity in methadone
      maintained patients. DESIGN: Velten's mood induction procedures were used to
      induce elative and depressive emotional reactions in the subjects. Each group was
      administered both induction procedures at 0 hour and 3 hours (corresponding with
      trough and peak plasma methadone concentrations in methadone subjects). SETTING:
      A drug treatment clinic with an out-patient methadone maintenance treatment
      programme. PARTICIPANTS: Twenty-one subjects currently on methadone maintenance
      treatment and 21 controls with no history of opioid dependence. MEASUREMENTS:
      Emotional reactivity was measured using mood visual analogue scales. FINDINGS: At
      0 hour, methadone and control subjects showed similar elation (methadone 13.2 +/-
      3.1 mean +/- standard error of the mean [SEM], control 14.4 +/- 3.7) and
      depression reactivity (methadone 23.6 +/- 5.0, control 25.1 +/- 5.0). However, at
      3 hours repeated measures showed that methadone subjects had significantly
      decreased depression reactivity (methadone 18.5 +/- 4.6, control 36.7 +/- 5.7; P
      = 0.021) and elation reactivity (methadone 4.4 +/- 1.9, control 19.0 +/- 2.4)
      compared to controls. CONCLUSIONS: Opioid addicts on methadone maintenance appear
      to be less reactive to mood induction at times of peak plasma methadone
      concentration than non-addict controls; this suggests that methadone blunts both
      elative and depressive emotional reactivity.

PMID- 21883604
TI  - Transition from first illicit drug use to first injection drug use among rural
      Appalachian drug users: a cross-sectional comparison and retrospective survival
      analysis.
AB  - AIM: The study's objectives were to characterize initiation of injection drug
      use, examine the independent association of specific substance use with injection
      drug use and determine factors associated with rates of transition from first
      illicit drug use to first injection among a sample of rural Appalachian drug
      users. DESIGN: Interview-administered questionnaires were administered to a
      sample of drug users recruited via respondent-driven sampling. SETTING:
      Appalachian Kentucky. PARTICIPANTS: Injection drug users (IDUs) (n = 394) and non
      IDUs (n = 109). MEASUREMENTS: Data were collected on substance use and years from
      age at initiation of illicit substance use to 'event' (initiation of injection or
      date of baseline interview for non-IDUs). Logistic regression and Cox regression
      were used to identify factors associated with life-time injection drug use and
      transition time to injection, respectively. FINDINGS: OxyContin((r)) was involved
      in nearly as many initiations to injection (48%), as were stimulants, other
      prescription opioids and heroin combined; for participants who initiated with
      OxyContin((r)), the median time from which they began OxyContin((r)) use to their
      first injection of OxyContin((r)) was 3 years. Adjusting for demographics, five
      prescription drugs (benzodiazepines, illicit methadone, oxycodone, OxyContin((r))
      and other opiates) were associated with an increased hazard for transitioning
      from first illicit drug use to first injection drug use (each at P < 0.01).
      CONCLUSIONS: In Appalachia, in the United States, the prescription opioid
      OxyContin((r)) is widely used non-medically and appears to show a particularly
      high risk of rapid transition to injection compared with the use of other illicit
      drugs.

PMID- 21883605
TI  - Cessation assistance reported by smokers in 15 countries participating in the
      International Tobacco Control (ITC) policy evaluation surveys.
AB  - AIMS: To describe some of the variability across the world in levels of quit
      smoking attempts and use of various forms of cessation support. DESIGN: Use of
      the International Tobacco Control Policy Evaluation Project surveys of smokers,
      using the 2007 survey wave (or later, where necessary). SETTINGS: Australia,
      Canada, China, France, Germany, Ireland, Malaysia, Mexico, the Netherlands, New
      Zealand, South Korea, Thailand, United Kingdom, Uruguay and United States.
      PARTICIPANTS: Samples of smokers from 15 countries. MEASUREMENTS: Self-report on
      use of cessation aids and on visits to health professionals and provision of
      cessation advice during the visits. FINDINGS: Prevalence of quit attempts in the
      last year varied from less than 20% to more than 50% across countries. Similarly,
      smokers varied greatly in reporting visiting health professionals in the last
      year (<20% to over 70%), and among those who did, provision of advice to quit
      also varied greatly. There was also marked variability in the levels and types of
      help reported. Use of medication was generally more common than use of
      behavioural support, except where medications are not readily available.
      CONCLUSIONS: There is wide variation across countries in rates of attempts to
      stop smoking and use of assistance with higher overall use of medication than
      behavioural support. There is also wide variation in the provision of brief
      advice to stop by health professionals.

PMID- 21883606
TI  - Engagement with opioid maintenance treatment and reductions in crime: a
      longitudinal national cohort study.
AB  - AIMS: This study investigates changes in criminal involvement among patients in
      opioid maintenance treatment (OMT) over a 7-year period prior to, during and
      after treatment, particularly in relation to differences in treatment engagement.
      DESIGN, SETTING AND PARTICIPANTS: Treatment data on all patients who started OMT
      in Norway between 1997 and 2003 (n = 3221) were cross-linked with national
      criminal records. The period of observation was divided into four phases; pre
      treatment, in-treatment, between treatments and post-treatment. FINDINGS: During
      OMT, rates of criminal convictions for the cohort were reduced to fewer than half
      of waiting-list levels [incidence rate (IR) 0.63 versus 1.57]. Patients in
      continuous treatment had the fewest convictions (IR 0.47) during treatment. The
      highest rates were found among patients out of treatment after several treatment
      episodes (IR 1.52). All groups had significantly fewer criminal convictions
      during treatment compared to before treatment. Staying in OMT for 2 years or more
      was associated with significantly reduced rates of convictions during treatment.
      Younger age and pre-treatment criminal convictions were associated with
      significantly (P < 0.001) more convictions during treatment. Those who left
      treatment, permanently or temporarily, relapsed into high levels of convictions
      outside treatment. CONCLUSIONS: Criminal activity appears to be reduced in Norway
      during opiate maintenance treatment. Younger age and prior history of criminal
      activity are important risk factors for continued criminal activity during
      treatment.

PMID- 21883608
TI  - Adolescent drinking, academic achievement and leisure time use by secondary
      education students in a rural area of Crete.
AB  - This study investigated the alcohol consumption of secondary education students
      and their relationship to school life and leisure time use with peers. A cross
      sectional survey was conducted in March 2007, and the study population consisted
      of 14- to 19-year-old students living in an agricultural area of Crete. The final
      sample consisted of 117 individuals (response rate 90.0%). A short previously
      validated self-completion questionnaire was used collecting information on:
      personal and family characteristics; school progress; leisure time activities and
      relations with other adolescents; and alcohol consumption. Alcohol consumption
      differed significantly between male (75.5%) and female (25.8%) students (P <
      0.001). Almost half of the participants (48.3%) reported alcohol consumption
      during nights out with friends. The mean grade for the previous year for students
      consuming alcohol was lower compared with those who did not, but the difference
      was not statistically significant (P = 0.066). Statistical evidence supported the
      hypothesis that students who consumed alcohol had more absences and this
      association was stronger for male students. The frequency of alcohol consumption
      was found to relate to the number of absences for both sexes. Male students who
      had been suspended from school were more likely to drink alcohol than those who
      had not been suspended. Statistical evidence also supported the hypotheses that
      students who spent their free time in cafeterias, bars or billiard halls were
      more likely to drink alcohol and also consume alcohol at higher frequencies than
      those that did not spend their free time this way (P = 0.002 and P < 0.001,
      respectively). More health education programmes and actions are needed at the
      national and local level to help students, families, schools, communities and the
      state better understand the real dimensions of the problem.

PMID- 21883609
TI  - A scoping review on the experiences and preferences in accessing diabetes-related
      healthcare information and services by British Bangladeshis.
AB  - Diabetes is a chronic condition requiring lifelong self-management. Patients are
      encouraged to access appropriate services to facilitate optimum management of
      diabetes. Although equitable access to healthcare in the United Kingdom is a
      legal right, not all groups and individuals in the community experience equity.
      Despite various equality laws and numerous efforts to minimise health
      inequalities related to access, particular community groups are more likely to
      experience inequitable access than others. The Bangladeshi community are one such
      community who experience some of the worst diabetes-related health outcomes in
      the United Kingdom. Little is known about their experiences and preferences in
      accessing diabetes healthcare information and services. Consequently, we
      undertook a scoping review of the literature by following the York Scoping
      Reviews Framework to identify the experiences and preferences of Bangladeshi
      patients and carers when gaining access to diabetes-related healthcare
      information and services. We identified eight articles and reported our results
      in relation to four domains of access: health service availability, health
      service utilisation, health service outcomes and the notion of equity. The review
      identified that language and literacy issues were the most common barriers
      hindering access to information and services. Patient knowledge regarding
      diabetes and its management was generally low, and friends and family were
      frequently being used as information sources and as informal interpreters.
      Additionally, there were feelings of isolation from mainstream information and
      services possibly resulting in the high prevalence of depression in the
      Bangladeshi community with women more affected than men. Social networks combined
      with religious and cultural beliefs as well as wider societal duties played a
      crucial role in accessing information and services for this population, and the
      identification of these issues merit further research and are possible avenues
      towards improved access to healthcare information and services for the
      Bangladeshi population.

PMID- 21883607
TI  - Psychiatric comorbidity and the persistence of drug use disorders in the United
      States.
AB  - AIMS: DSM-IV drug use disorders, a major public health problem, are highly
      comorbid with other psychiatric disorders, but little is known about the role of
      this comorbidity when studied prospectively in the general population. Our aims
      were to determine the role of comorbid psychopathology in the 3-year persistence
      of drug use disorders. DESIGN AND SETTING: Secondary data analysis using waves 1
      (2001-02) and 2 (2005-05) of the National Epidemiologic Survey on Alcohol and
      Related Conditions. PARTICIPANTS: Respondents with current DSM-IV drug use
      disorder at wave 1 who participated in wave 2 (n = 613). MEASUREMENTS: Alcohol
      Use Disorders and Associated Disabilities Interview Schedule IV (AUDADIS-IV)
      obtained DSM-IV Axis I and II diagnoses. Persistent drug use disorder was defined
      as meeting full criteria for any drug use disorder between waves 1 and 2.
      FINDINGS: Drug use disorders persisted in 30.9% of respondents. No Axis I
      disorders predicted persistence. Antisocial [odds ratio (OR) = 2.75; 95%
      confidence interval (CI): 1.27-5.99], borderline (OR = 1.91; 95% CI: 1.06-3.45)
      and schizotypal (OR = 2.77; 95% CI: 1.42-5.39) personality disorders were
      significant predictors of persistent drug use disorders, controlling for
      demographics, psychiatric comorbidity, family history, treatment and number of
      drug use disorders. Deceitfulness and lack of remorse were the strongest
      antisocial criteria predictors of drug use disorder persistence, identity
      disturbance and self-damaging impulsivity were the strongest borderline criteria
      predictors, and ideas of reference and social anxiety were the strongest
      schizotypal criteria predictors. CONCLUSIONS: Antisocial, borderline and
      schizotypal personality disorders are specific predictors of drug use disorder
      persistence over a 3-year period.

PMID- 21883610
TI  - Adaptive speciation and sexual dimorphism contribute to diversity in form and
      function in the adaptive radiation of Lake Matano's sympatric roundfin sailfin
      silversides.
AB  - The utility of traits involved in resource exploitation is a central criterion
      for the adaptive character of radiations. Here, we test for differentiation in
      morphology, jaw mechanics and nutrition among species and sexes of Lake Matano's
      sympatric 'roundfin' sailfin silversides. The three incipient fish species differ
      significant in several candidate traits for adaptation following ecological
      selection pressure, corresponding to contrasting jaw mechanics and distinct
      patterns in food resource use. These findings are consistent with functional
      adaptation and suggest divergence following alternative modes of feeding
      specialization. Further, intersexual resource partitioning and corresponding
      adaptation in jaw mechanics is evident in two of the three incipient species,
      demonstrating that sexual dimorphism contributes to the ecomorphological and
      trophic diversity of the emerging radiation. This is, to the best of our
      knowledge, the first study reporting interspecific as well as intersexual
      adaptation by alternative modes of form and function in an evolving fish species
      flock.

PMID- 21883611
TI  - Complex selection associated with Hox genes in a natural population of lizards.
AB  - Hox genes are recognized for their explanatory power of bilateral development.
      However, relatively little is known about natural variation in, and the
      evolutionary dynamics of, Hox genes within wild populations. Utilizing a natural
      population of sand lizards (Lacerta agilis), we screened HoxA13 for genetic
      variation and an association with incidence of offspring malformations. We found
      significant effects of parental genetic similarity and offspring sex, and their
      interaction, on risk of hatching malformed as an offspring. We also found within
      population genetic variation in HoxA13, and identified a significant effect of a
      three-way interaction among Hox genotype, parental genetic similarity, and
      offspring sex on the risk of hatching malformation. Since malformed offspring in
      this population do not survive to maturity, this study reveals complex and
      ongoing selection associated with Hox genes in a wild reptile population.
      Importantly, this demonstrates the utility of natural populations in unveiling
      microevolutionary processes shaping variation in highly conserved genes.

PMID- 21883613
TI  - Evolutionary reduction of developmental plasticity in desert spadefoot toads.
AB  - Organisms vary their rates of growth and development in response to environmental
      inputs. Such developmental plasticity may be adaptive and positively correlate
      with environmental heterogeneity. However, the evolution of developmental
      plasticity among closely related taxa is not well understood. To determine the
      evolutionary pattern of plasticity, we compared plasticity in time to and size at
      metamorphosis in response to water desiccation in tadpoles among spadefoot
      species that differ in breeding pond and larval period durations. Like most
      tadpoles, spadefoot tadpoles possess the remarkable ability to accelerate
      development in response to pond drying to avoid desiccation. Here, we hypothesize
      that desert spadefoot tadpoles have evolved reduced plasticity to avoid
      desiccation in ephemeral desert pools compared to their nondesert relatives that
      breed in long-duration ponds. We recorded time to and size at metamorphosis
      following experimental manipulation of water levels and found that desert-adapted
      species had much less plasticity in larval period and size at metamorphosis than
      nondesert species, which retain the hypothetical ancestral state of plasticity.
      Furthermore, we observed a correlation between degree of plasticity and fat body
      content that may provide mechanistic insights into the evolution of developmental
      plasticity in amphibians.

PMID- 21883612
TI  - The fitness of drug-resistant malaria parasites in a rodent model: multiplicity
      of infection.
AB  - Malaria infections normally consist of more than one clonally replicating
      lineage. Within-host interactions between sensitive and resistant parasites can
      have profound effects on the evolution of drug resistance. Here, using the
      Plasmodium chabaudi mouse malaria model, we ask whether the costs and benefits of
      resistance are affected by the number of co-infecting strains competing with a
      resistant clone. We found strong competitive suppression of resistant parasites
      in untreated infections and marked competitive release following treatment. The
      magnitude of competitive suppression depended on competitor identity. However,
      there was no overall effect of the diversity of susceptible parasites on the
      extent of competitive suppression or release. If these findings generalize, then
      transmission intensity will impact on resistance evolution because of its effect
      on the frequency of mixed infections, not because of its effect on the
      distribution of clones per host. This would greatly simplify the computational
      problems of adequately capturing within-host ecology in models of drug resistance
      evolution in malaria.

PMID- 21883614
TI  - Intraspecific variation in behaviour: effects of evolutionary history,
      ontogenetic experience and sex.
AB  - Geographical variation in behaviour within species is common. However, how
      behavioural plasticity varies between and within locally adapted populations is
      less studied. Here, we studied behavioural plasticity induced by perceived
      predation risk and food availability in pond (low predation - high competition)
      vs. coastal marine (high predation - low competition) nine-spined sticklebacks
      (Pungitius pungitius) reared in a common garden experiment. Pond sticklebacks
      were more active feeders, more risk-taking, aggressive and explorative than
      marine sticklebacks. Perceived predation risk decreased aggression and risk
      taking of all fish. Food restriction increased feeding activity and risk-taking.
      Pond sticklebacks became more risk-taking than marine sticklebacks under food
      shortage, whereas well-fed fish behaved similarly. Among poorly fed fish, males
      showed higher drive to feed, whereas among well-fed fish, females did. Apart from
      showing how evolutionary history, ontogenetic experience and sex influence
      behaviour, the results provide evidence for habitat-dependent expression of
      adaptive phenotypic plasticity.

PMID- 21883615
TI  - Head shape evolution in Gymnophthalmidae: does habitat use constrain the
      evolution of cranial design in fossorial lizards?
AB  - Habitat usage comprises interactions between ecological parameters and organismal
      capacities, and the selective pressures that ultimately determine the outcome of
      such processes in an evolutionary scale may be conflicting when the same
      morphological structure is recruited for different activities. Here, we
      investigate the roles of diet and locomotion in the evolution of cranial design
      in gymnophthalmid lizards and test the hypothesis that microhabitat use drives
      head shape evolution, particularly in head-first burrowers. Morphological factors
      were analysed in relation to continuous ecological indexes (prey hardness and
      substrate compactness) using conventional and phylogenetic approaches. Results
      suggest that the evolution of head morphology in Gymnophthalmidae was shaped
      under the influence of microhabitat use rather than diet: burrowers have shorter
      heads with lower rostral angulation, independently of the prey consumed. Food
      preferences appear to be relatively conserved throughout the phylogeny of the
      group, which may have permitted the extensive radiation of gymnophthalmids into
      fossorial microhabitats.

PMID- 21883616
TI  - Human papillomavirus in adolescents: lessons learned from decades of evaluation.
AB  - Knowledge regarding the natural history of human papillomavirus (HPV) infection
      and its clinical sequelae in adolescents has increased significantly over the
      last decade; as a result, there have been world-wide recommendations for less
      aggressive Pap screening and management of cervical dysplasias in young women. It
      is important that adolescent health providers understand these issues, as
      knowledge of HPV and its sequelae in the Australian community is limited, despite
      the introduction of a national immunisation programme. Parents and young women
      have expressed a desire for further information to make informed choices. This
      paper reviews the natural history of HPV infection in adolescents and the
      evidence behind new conservative guidelines for cervical screening, plus
      prophylactic vaccination in young women.

PMID- 21883617
TI  - Ectoplacental cone induces resistance to apoptosis in high doses of interferon
      (IFN)-gamma-treated decidual cells.
AB  - PROBLEM In this study, we explored the relationship between decidual cells (DC)
      and interferon (IFN)-gamma, in the presence or absence of ectoplacental cone (EC)
      using a coculture system. METHOD OF STUDY  Decidual cells and EC were isolated
      from pregnant mice on gestation day 7.5. DCs were cultured for 48 hr and then
      treated with fresh EC. After characterization, they were treated with IFN-gamma,
      and cell death was evaluated. RESULTS  Interferon-gamma drastically increased
      decidual apoptosis, which was partially reverted by the addition of EC to the IFN
      gamma-treated decidual culture. Moreover, the addition of EC to non-treated DC
      cultures was also capable of attenuating death rates. CONCLUSION Resistance to
      apoptosis may be induced in DC by the EC. This suggests that EC may participate
      in the inhibition of IFN-gamma-dependent apoptosis and, therefore, play important
      role for DC survival in a cytokine-enriched placental environment.

PMID- 21883618
TI  - Blood exposures ignored in racial disparities in HIV prevalence.

PMID- 21883619
TI  - Modulation of hepatocyte growth factor secretion in human female reproductive
      tract stromal fibroblasts by poly (I:C) and estradiol.
AB  - PROBLEM: Hepatocyte Growth Factor (HGF) secretion facilitates epithelial cell
      growth and development in the female reproductive tract (FRT) and may contribute
      to pathological conditions such as cancer and endometriosis. We hypothesized that
      estradiol and poly (I:C), a synthetic RNA mimic, may have a regulatory effect on
      HGF secretion by stromal fibroblasts from FRT tissues. METHOD OF STUDY: Following
      hysterectomies, normal tissue from the uterus, endocervix, and ectocervix were
      dispersed into stromal cell fractions by enzymatic digestion and differential
      filtering. Stromal fibroblasts were cultured and treated with estradiol and/or
      poly (I:C), and conditioned media were analyzed for HGF via enzyme-linked
      immunosorbent assay. RESULTS: Treating uterine fibroblasts with estradiol or poly
      (I:C) significantly increased HGF secretion. When uterine fibroblasts were co
      treated with estradiol and poly (I:C), the effect on HGF secretion was additive.
      In contrast, stromal fibroblasts from endo- and ecto-cervix were unresponsive to
      estradiol, but were stimulated to secrete HGF by poly (I:C). CONCLUSION: HGF
      secretion is uniquely regulated in the uterus, but not in ecto- and endo-cervix,
      by estradiol. Moreover, potential viral pathogens further induce HGF. These
      findings have potential applications in understanding both hormonal regulation of
      normal tissue as well as the role of HGF in tumorogenesis, endometriosis, and
      human immunodeficiency virus infection.

PMID- 21883620
TI  - Expression of TLR 2, TLR 4 and iNOS in cervical monocytes of Chlamydia
      trachomatis-infected women and their role in host immune response.
AB  - PROBLEM: To study the innate immune response -TLR2 TLR 4 and iNOS expression in
      female genital Chlamydia trachomatis infection. METHOD: TLR 2, TLR 4, and iNOS
      expression was evaluated by real-time PCR in C. trachomatis-infected
      asymptomatic, mucopurulent cervicitis (MPC), and fertility disorders (FD) women.
      Expression of TLR signaling pathway genes was checked in vivo in C. trachomatis
      infected cervical monocytes. Further, inos gene expression and nitric oxide
      release was assessed in vitro in THP-1 cell line upon chlamydial infection.
      RESULTS: TLR2, TLR4, and iNOS expression was significantly (P < 0.05) higher in
      C. trachomatis-positive women with FD, MPC, and asymptomatic women, respectively,
      than in control. Chlamydial infection significantly upregulates CD86, TLR4,
      MyD88, IRAK2, nF-kappaB, IL-1,beta and IL-12 genes. Expression of iNOS gene was
      found to be significantly (P < 0.05) high 12 hrs post-infection. CONCLUSIONS:
      Chlamydia trachomatis stimulates innate immune cells by activation of TLR2/TLR 4.
      Overall data indicate that recognition by TLR4 helps in initiation of immune
      response while recognition by TLR2 leads to secretion of inflammatory cytokines
      while iNOS-induced nitric oxide production helps in clearing Chlamydia. These
      results are first to provide initial insights into how innate immune response
      operates in human cervical monocytes upon chlamydial infection.

PMID- 21883621
TI  - Intra-arterial tenecteplase for treatment of acute ischemic stroke: feasibility
      and comparative outcomes.
AB  - OBJECTIVE: Tenecteplase (TNK) is a third-generation thrombolytic agent. We
      evaluated the safety and feasibility of intra-arterial (IA) administration of TNK
      in patients with acute ischemic stroke. METHODS: Patients who received
      endovascular treatment for acute ischemic stroke were identified from
      prospectively collected databases at three university hospitals. We compared
      clinical and radiological outcomes of patients treated with TNK to those treated
      with other IA thrombolytics or mechanical thrombectomy alone. Primary outcome
      measures were favorable functional outcome at 30 days (modified Rankin Scale
      score of 0-2), and rate of intracranial hemorrhage (ICH). Early neurological
      improvement, angiographic recanalization, time to recanalization, and mortality
      at 30 days were additional outcome measures. RESULTS: We identified 114 patients
      (mean age 67 +/- 15 years, 54 were women). Thirty-three patients received IA TNK,
      48 received alteplase (n = 11) or reteplase (n = 37), and 33 patients had
      mechanical thrombectomy alone. Stroke severity was similar among the three
      groups. No difference between the groups was found in the secondary outcome
      measures and ICH. Borderline statistical significance was seen toward favorable
      functional outcome at 1 month in the TNK-treated patients [odds ratio (OR) = 2.8;
      95% confidence interval (CI) .96-8.1, P = .063 vs. other thrombolytics, and OR =
      3.0, 95% CI .97-9.5, P = .06 vs. mechanical thrombectomy alone]. CONCLUSION: Our
      study demonstrates that administration of IA TNK in acute stroke is safe and
      results in rates of favorable outcomes that are comparable to those observed with
      currently used drugs. Additional studies are needed to further determine the
      safety and efficacy of IA TNK in acute stroke treatment.

PMID- 21883622
TI  - Preliminary MRI quality assessment and device acceptance guidelines for a
      multicenter bioclinical study: the GO Glioblastoma Project.
AB  - It is a major challenge to guarantee homogeneous acquisition during a prospective
      multicenter magnetic resonance imaging (MRI) study that makes use of different
      devices. The goal of the multicenter Grand Ouest Glioblastoma Project (GOGP) was
      to correlate MRI quantitative parameters with biological markers extracted from
      image-guided biopsies. Therefore, it was essential to ensure spatial coherence of
      the parameters as well as the signal intensity and homogeneity. The project
      included the same MRI protocol implemented on six devices from different
      manufacturers. The key point was the initial acceptance of the imaging devices
      and protocol sequences. For this purpose, and to allow comparison of quantitative
      patient data, we propose a specific method for quality assessment. A common
      quality control based on 10 parameters was established. Three pulse sequences of
      the clinical project protocol were applied using three test-objects. A fourth
      test-object was used to assess T1 accuracy. Although geometry-related parameters,
      signal-to-noise ratio, uniformity, and T1 measurements varied slightly depending
      on the different devices, they nevertheless remained within the recommendations
      and expectations of the multicenter project. This kind of quality control
      procedure should be undertaken as a prerequisite to any multicenter clinical
      project involving quantitative MRI and comparison of data acquisitions with
      quantitative biological image-guided biopsies.

PMID- 21883625
TI  - Gliosarcoma metastatic to the leptomeninges and dura.
AB  - We describe a rare case of a patient with left frontotemporal gliosarcoma, which
      metastasized through the cerebrospinal fluid (CSF) to the leptomeninges and
      pachymeninges. Pathologically confirmed, magnetic resonance imaging-visible
      leptomeningeal spread of gliosarcoma via the CSF has not been previously
      reported.

PMID- 21883624
TI  - Sonographic assessment of the optic nerve sheath and transorbital monitoring of
      treatment effects in a patient with spontaneous intracranial hypotension: case
      report.
AB  - OBJECTIVE: To investigate the potential of the ultrasound-based evaluation of the
      optic nerve sheath in a patient with spontaneous intracranial hypotension due to
      cervical cerebrospinal fluid (CSF) leakage. METHODS: Repeated measurements of the
      optic nerve sheath diameter (ONSD) using B-mode sonography were performed before
      treatment initiation, during medical treatment, and during a course of repeated
      placement of epidural blood patches. RESULTS: On admission, transorbital
      sonography revealed a decreased ONSD of 4.1 mm on the right and 4.3 mm on the
      left side. After 8 months of treatment with caffeine and computed tomography
      guided epidural blood patches a gradual distension of the ONSD into the normal
      range was bilaterally observed (right: 5.2 mm; left: 5.3 mm). CONCLUSIONS: The
      ultrasound-based evaluation of the optic nerve sheath may be helpful in detecting
      CSF hypovolemia and for determination of treatment effects. This report should be
      seen as a basis for future investigations on the sonographic assessment of the
      optic nerve sheath in diagnosis and treatment of intracranial hypotension.

PMID- 21883626
TI  - Endovascular cerebral protection and revascularization of innominate artery
      stenosis through single-site access, with device entrapment and rescue: technical
      case report.
AB  - We describe a novel technique for cerebral embolic device placement with
      inadvertent entrapment and subsequent rescue in the endovascular treatment of
      innominate artery stenosis. A 62-year-old female presented with symptomatic right
      sided subclavian steal syndrome. Single-site access for revascularization of
      critical innominate artery stenosis with simultaneous cerebral embolic protection
      performed for this diagnosis has not been previously reported. Initial nontarget
      self-expanding stent deployment within the right subclavian artery resulted in
      entrapment of the embolic protection device. The device was retrieved through
      snare fixation and resheathing within a 6-French guide catheter navigated through
      common femoral artery access. Innominate artery balloon-mounted stent angioplasty
      was performed preceded by the embolic device retrieval, with complete resolution
      of symptoms. Endovascular distal protection device placement for prevention of
      cerebral atherothromboembolism during innominate artery stent angioplasty is not
      without risk and utilization needs to be carefully considered. 

PMID- 21883627
TI  - The correlation between Spurling test and imaging studies in detecting cervical
      radiculopathy.
AB  - BACKGROUND: Cervical spine symptoms are a major cause of visits to general or
      spinal orthopedic surgeons or even primary care physicians. Although in this era
      the imaging studies can precisely rule out or diagnose pathologies in the spine,
      all of these studies have limitations. Computerized tomography (CT) scan consists
      of radiation exposure to the patients and it should be done with caution.
      Magnetic resonance imaging (MRI) is a highly effective imaging tool, but in many
      countries it is still costly. The goal of our study was to determine whether a
      simple clinical test can help the clinician to identify the patients who need to
      be sent for these imaging studies. METHODS: Two hundred fifty-seven patients with
      clinical cervical radiculopathy underwent complete physical examination that also
      included the Spurling test. After that, all patients were sent to imaging studies
      of the cervical spine (CT and/or MRI). Correlation between the physical
      examination using the Spurling test to the imaging studies was done. RESULTS:
      Sensitivity of the Spurling test to nerve root pathology was 95% and specificity
      was 94%. CONCLUSION: This paper demonstrate that patients with positive Spurling
      test have probable nerve root pressure and should be sent for further imaging
      studies. In patients with negative Spurling test, the possibility of nerve root
      pressure is less likely.

PMID- 21883628
TI  - Determination of language dominance: Wada test and fMRI compared using a novel
      sentence task.
AB  - BACKGROUND AND PURPOSE: This study aimed to develop a new linguistic based
      functional magnetic resonance imaging (fMRI)-sentence decision task that reliably
      detects hemispheric language dominance. METHODS: FMRI was performed in 13 healthy
      right-handed controls and 20 patients at 1.5 T prior to neurosurgery. The main
      components of language were assessed with different paradigms (rhyme, synonym,
      and sentence). In controls, activations were quantified by a volume of interest
      analysis. Four neuroimagers tested a visual rating score in the patients group.
      Interrater agreement and concordance between fMRI and Wada test were calculated.
      RESULTS: In healthy controls, the frontal language area was activated by the
      sentence and synonym task in 100% and in 73% by the rhyme task. The temporal
      language area was activated in 100% by the sentence-, in 64% by the synonym, and
      in 55% by the rhyme task. In the patients group, interrater agreement was .90 for
      activations in the inferior frontal and .97 in the superior temporal gyrus.
      Correlation between the WADA test and fMRI was .86 for the sentence, and .89 for
      the synonym task. CONCLUSIONS: The sentence task provides robust activations in
      putative essential language areas and can be used for visual analysis of
      predefined areas to facilitate interpretation of clinical fMRI.

PMID- 21883629
TI  - Program director perceived factors for an enhanced advanced education program in
      prosthodontics recall system.
AB  - PURPOSE: A survey study of program directors in Advanced Education Programs in
      Prosthodontics (AEPPs) was conducted to determine the barriers to and factors
      that can lead to an enhanced patient-centered recall system. MATERIAL AND
      METHODS: Surveys were sent to AEPP directors across the United States to assess
      their program's recall protocol. This survey first identified whether an active
      recall program existed. Based on the existence of recall, the survey then delved
      into benefits of recall systems for patients and residents, barriers to the
      formation of a successful recall system, and factors that can be improved upon
      for an enhanced recall system. RESULTS: Thirty-two of the 45 programs responded;
      however, only 28 of the surveys were completed entirely, giving a response rate
      of 62%. Of these 32 programs, 19 (59.4%) reported having a recall system. A
      majority of the AEPPs with recall (87.5%) indicated that their system can be
      further improved. Almost all of the programs without recall (91.7%) indicated
      that if solutions to the most common barriers to recall were found, they would
      like to implement one within their program. Some hindrances faced by all programs
      included budget for initiating and maintaining a recall system, personnel to
      perform hygiene, a patient tracking system, patient education, and time
      allocation in the residents' curriculum. Mann-Whitney analyses indicated no
      statistically significant difference in each factor between programs with and
      without a recall system. Power analysis suggested that differences in perceived
      barriers between programs with and without recall systems may have been found if
      the response rate was 71% or greater. Necessary budget and facilities for
      initiating or maintaining a recall system may be the greatest difference in
      barrier importance between programs with and without recall. CONCLUSIONS:
      Prosthodontic program directors perceived their program's recall system could be
      improved. If solutions to the most common hindrances were found, almost all
      program directors desired to establish a recall system within their AEPP.
      Therefore, a pilot recall system could be valuable in identifying these solutions
      in establishing an effective recall system for prosthodontic programs within the
      context of patient health promotion, program curriculum, and financial
      ramifications.

PMID- 21883630
TI  - Bisphosphonate therapy for skeletal malignancies and metastases: impact on jaw
      bones and prosthodontic concerns.
AB  - Healthy jawbones ensure better tooth anchorage and the ability to masticate and
      maintain metabolism. This is achieved by a delicate balance between bone
      formation and resorption in response to functional demands. An imbalance in the
      expression of receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL)
      and osteoprotegerin (OPG) or osteoclastogenesis inhibitory factor (OCIF) is
      believed to be the underlying mechanism of osteolysis in metastases, multiple
      myelomas, and cancer therapy-induced bone loss in patients. Considered mainly as
      bone-specific agents to treat postmenopausal osteoporosis, bisphosphonates, in
      combination with certain chemotherapeutic agents have proved to be effective in
      prevention of tumor formation and metastatic osteolysis in bone tissue.
      Osteonecrosis of the jaws associated with them has, however, been of grave
      concern to the prosthodontist, as it predisposes patients to a bone-deficient
      basal seat for dental prostheses. This manuscript reviews available information
      over the past 13 years on possible mechanisms of bone loss, bisphosphonate
      induced osteonecrosis of jaw bones, and prosthodontic concerns.

PMID- 21883631
TI  - Pre-prosthetic orthodontic treatment using personalized elastic separators for
      optimization of emergence profile in esthetic crowns: a clinical report.
AB  - Restoring a misaligned tooth with an inadequate contact point is a challenge to
      the practitioner. In some instances, teeth that could be repositioned and
      adequately restored are extracted. Thus, the aim of this article was to describe
      a treatment using orthodontic and prosthetic techniques to restore esthetics and
      function in a patient with a distally drifted maxillary lateral incisor. The
      patient's functional and esthetic expectations were successfully met with the
      outlined treatment.

PMID- 21883632
TI  - A technique for repairing a loosening abutment screw for a cement-retained
      implant prosthesis.
AB  - Prostheses may be attached to implants or implant abutments using screw retention
      or cementation. With the increased use of cement-retained, implant-supported
      restorations for the replacement of missing teeth, clinicians may choose to use a
      definitive cement to lute the definitive restoration. Loosening of an abutment
      screw is a challenging complication of cement-retained, implant-supported
      prosthetic restorations. Often, the abutment screw becomes loose from the implant
      body, whereas the crown remains cemented to the abutment. In such situations,
      separating the cemented crown from the underlying abutment or locating the
      abutment-screw access for removal of the restoration is a difficult task. The
      purpose of this report is to describe a simple technique for locating the
      abutment-screw access in the event of its loosening. The advantage of this
      technique is that it can facilitate easy location of the abutment screw, thus
      minimizing damage to the existing restoration and allowing it to be reused.

PMID- 21883633
TI  - High-resolution electron microscopical study of cyst walls of Entamoeba spp.
AB  - Knowledge of the fine structural organization, molecular composition and
      permeability properties of the cell surface of intestinal protozoan cysts is
      important to understand the biologic basis of their resistance. Recent studies on
      the biology of the cyst walls of Entamoeba histolytica and Entamoeba invadens
      have considerably advanced knowledge on the cellular processes involved in the
      transport and surface deposition of the main cyst wall components. Using
      transmission electron microscopy, cytochemistry, scanning electron microscopy and
      freeze-fracture techniques, we have obtained new information. In mature cysts the
      permeability of Entamoeba cysts is limited to small molecules not by the cyst
      wall, but by the plasma membrane, as demonstrated with the use of ruthenium red
      as an electron-dense tracer. Cell walls of E. histolytica cysts are made up of
      five to seven layers of unordered fibrils 7-8 nm thick. Alcian blue stains a
      regular mesh of fibrils approximately 4 nm thick, running perpendicularly to the
      cyst wall. In addition, abundant ionogenic groups are seen in cyst walls treated
      with cationized ferritin. In the mature cysts of E. histolytica and E. invadens
      small cytoplasmic vesicles with granular material were in close contact with the
      plasma membrane, suggesting a process of fusion and deposition of granular
      material to the cell wall. The plasma membrane of mature cysts is devoid of
      intramembrane particles when analyzed with the freeze-fracture technique. When
      viewed with scanning electron microscopy the surface of E. histolytica cysts
      clearly differs from that of Entamoeba coli and E. invadens.

PMID- 21883634
TI  - Guidelines for the naming of genes, gene products, and mutants in the
      opportunistic protists.
AB  - The opportunistic protists encompass a wide diversity of organisms including
      Pneumocystis, Toxoplasma, cryptosporidia, microsporidia, and related genera.
      Recent advances in the molecular biology and cellular biochemistry of these
      organisms have led to the identification of an ever growing numbers of key genes
      and their cognate proteins. Until now, these molecules have not been designated
      using any consistent nomenclature system, leading to considerable confusion. The
      participants of the 11th International Workshop on Opportunistic Protists met on
      August 3, 2010 to reach consensus of a nomenclature system for genes, gene
      products, and mutants in the opportunistic protists. The following summary
      reports the consensus agreement to move toward a unified nomenclature system for
      these organisms. The system is adapted from that used for Saccharomyces
      cerevisiae.

PMID- 21883635
TI  - A prospective comparison of procedural sedation and ultrasound-guided
      interscalene nerve block for shoulder reduction in the emergency department.
AB  - OBJECTIVES: Emergency physicians (EPs) are beginning to use ultrasound (US)
      guidance to perform regional nerve blocks. The primary objective of this study
      was to compare length of stay (LOS) in patients randomized to US-guided
      interscalene block or procedural sedation to facilitate reduction of shoulder
      dislocation in the emergency department (ED). The secondary objectives were to
      compare one-on-one health care provider time, pain experienced by the patient
      during reduction, and patient satisfaction between the two groups. METHODS: This
      was a prospective, randomized study of patients presenting to the ED with
      shoulder dislocation. The study was conducted at an academic Level I trauma
      center ED with an annual census of approximately 80,000. Patients were eligible
      for the study if they were at least 18 years of age and required reduction of a
      shoulder dislocation. A convenience sample of patients was randomized to either
      traditional procedural sedation or US-guided interscalene nerve block. Procedural
      sedation was performed with etomidate as the sole agent. Interscalene blocks were
      performed by hospital-credentialed EPs using sterile technique and a SonoSite
      MicroMaxx US machine with a high-frequency linear array transducer. Categorical
      variables were evaluated using Fisher's exact test, and continuous variables were
      analyzed using the Wilcoxon rank sum test. RESULTS: Forty-two patients were
      enrolled, with 21 patients randomized to each group. The groups were not
      significantly different with respect to sex or age. The mean (+/-SD) LOS in the
      ED was significantly higher in the procedural sedation group (177.3 +/- 37.9 min)
      than in the US-guided interscalene block group (100.3 +/- 28.2 minutes; p <
      0.0001). The mean (+/-SD) one-on-one health care provider time was 47.1 (+/-9.8)
      minutes for the sedation group and 5 (+/-0.7) minutes for the US-guided
      interscalene block group (p < 0.0001). There was no statistically significant
      difference between the two groups in patient satisfaction or pain experienced
      during the procedure. There were no significant differences between groups with
      respect to complications such as hypoxia or hypotension (p = 0.49). CONCLUSIONS:
      In this study, patients undergoing shoulder dislocation reduction using US-guided
      interscalene block spent less time in the ED and required less one-on-one health
      care provider time compared to those receiving procedural sedation. There was no
      difference in pain level or satisfaction when compared to procedural sedation
      patients.

PMID- 21883636
TI  - The academic chair in emergency medicine: current demographics and survey results
      identifying the skills and characteristics desired for the role.
AB  - OBJECTIVES: Due to the rapid growth in academic emergency departments over the
      past 20 years, recent significant changes in leadership have occurred. To prepare
      for future transitions, leaders in academic emergency medicine (EM) should
      identify those skills and characteristics desired in future academic chairs. The
      authors sought to determine which skills and characteristics are more important
      than others to help guide the development of EM-specific leadership courses.
      METHODS: A survey of the current academic chairs in EM included questions
      pertaining to demographics, career time course, expected career longevity, and
      ratings of skills and characteristics deemed necessary for academic chairs.
      Chairs were asked to rate the qualities twice, to identify qualities that must be
      obtained prior to becoming chair, and those that may be obtained during chair
      tenure. RESULTS: Ninety-seven percent of the membership of the Association of
      Academic Chairs in Emergency Medicine (AACEM) completed the survey. Most chairs
      have been in practice for over 15 years, and a minority, for less than 10 years.
      One-third predict less than 6 more years in their current position, and almost
      50% predict their careers as chair will continue an additional 6-10 years. The
      highest-rated formal training was an administrative or leadership training course
      or certification. Chairs noted that academic experience (including scholarly
      productivity, peer-reviewed publication, faculty development, and graduate
      medical education) was the most important skill set to obtain prior to becoming a
      chair, while hospital governance and cross-departmental collaboration skills can
      be obtained once in the role. Managerial skills were also felt to be of
      importance. Personal characteristics were overall rated highly. No differences
      were found between responses from early chairs and those later in their careers.
      CONCLUSIONS: Leadership courses for aspiring chairs in EM should foster the
      development of academic experience and managerial skills. Advanced degrees in
      leadership or administration are highly desirable in future chairs.

PMID- 21883637
TI  - Arriving by emergency medical services improves time to treatment endpoints for
      patients with severe sepsis or septic shock.
AB  - OBJECTIVES: The objective was to evaluate the effect of arrival to the emergency
      department (ED) by emergency medical services (EMS) on time to initiation of
      antibiotics, time to initiation of intravenous fluids (IVF), and in-hospital
      mortality in patients with severe sepsis and septic shock. METHODS: The authors
      performed an evaluation of prospectively collected registry data of patients with
      a diagnosis of severe sepsis or septic shock who presented to an urban academic
      ED during a 2-year period from January 1, 2005, to December 31, 2006. Descriptive
      and multivariate analytic methods were used to analyze the data. Using unadjusted
      and adjusted models, out-of-hospital patients who presented to the ED by
      ambulance (EMS) were compared to control patients who arrived by alternative
      means (non-EMS). Primary outcomes measured were ED time to initiation of
      antibiotics, ED time to initiation of IVF, and in-hospital mortality. RESULTS: A
      total of 963 severe sepsis patients were enrolled in the registry. Median time to
      antibiotics was 116 minutes for EMS (interquartile range [IQR] = 66 to 199) vs.
      152 minutes for non-EMS (IQR = 92 to 252, p <= 0.001). Median time to initiation
      of IVF was 34 minutes for EMS (IQR = 10 to 88) and 68 minutes for non-EMS (IQR =
      25 to 121, p <= 0.001). After adjustment for the Acute Physiology and Chronic
      Health Evaluation II (APACHE II) score, age, and initial serum lactate level, no
      significant differences in hospital mortality were seen (adjusted relative risk
      [aRR] for EMS vs. non EMS = 1.24, 95% confidence interval [CI] = 0.92 to 1.66, p
      = 0.16). The Cox proportional hazard ratio (HR) comparing EMS to non-EMS care
      after similar adjustment was HR = 1.27 for IVF (95% CI = 1.10 to 1.47, p = 0.004)
      and HR = 1.25 for antibiotics (95% CI = 1.08 to 1.44, p = 0.003). CONCLUSIONS:
      Out-of-hospital care was associated with improved in-hospital processes for the
      care of critically ill patients. Despite shortened ED treatment times for septic
      patients who arrive by EMS, a mortality benefit could not be demonstrated.

PMID- 21883638
TI  - National study of emergency department observation services.
AB  - OBJECTIVES: The objective was to describe patient and facility characteristics of
      emergency department (ED) observation services in the United States. METHODS: The
      authors analyzed the 2007 National Hospital Ambulatory Medical Care Survey
      (NHAMCS). Characteristics of EDs with observation units (OUs) were compared to
      those without, and patients with a disposition of ED observation were compared to
      those with a "short-stay" (<48 hour) hospital admission. Results are descriptive
      and without formal statistical comparisons for this observational analysis.
      RESULTS: An estimated 1,746 U.S. EDs (36%) reported having OUs, of which 56% are
      administratively managed by ED staff. Fifty-two percent of hospitals with ED
      managed OUs are in an urban location, and 89% report ED boarding, compared to 29
      and 65% of those that do not have an OU. The admission rate is 38% at those with
      ED-managed OUs and 15% at those without OUs. Of the 15.1% of all ED patients who
      are kept in the hospital following an ED visit, one-quarter are kept for either a
      short-stay admission (1.8%) or an ED observation admission (2.1%). Most (82%) ED
      observation patients were discharged from the ED. ED observation patients were
      similar to short-stay admission patients in terms of age (median = 52 years for
      both, interquartile range = 36 to 70 years), self-pay (12% vs. 10%), ambulance
      arrival (37% vs. 36%), urgent/emergent triage acuity (77% vs. 74%), use of >=1 ED
      medication (64% vs.76%), and the most common primary chief complaints and primary
      diagnoses. CONCLUSIONS: Over one-third of U.S. EDs have an OU. Short-stay
      admission patients have similar characteristics as ED observation patients and
      may represent an opportunity for the growth of OUs.

PMID- 21883639
TI  - Clinicopathological conference: a deadly cause of seizures in a 67-year-old
      alcoholic.

PMID- 21883640
TI  - Non-invasive assessment of skin microvascular function in humans: an insight into
      methods.
AB  - For more than two decades, methods for the non-invasive exploration of cutaneous
      microcirculation have been mainly based on optical microscopy and laser Doppler
      techniques. In this review, we discuss the advantages and drawbacks of these
      techniques. Although optical microscopy-derived techniques, such as nailfold
      videocapillaroscopy, have found clinical applications, they mainly provide
      morphological information about the microvessels. Laser Doppler techniques
      coupled with reactivity tests are widespread in the field of microvascular
      function research, but many technical issues need to be taken into account when
      performing these tests. Post-occlusive reactive hyperemia and local thermal
      hyperemia have been shown to be reliable tests, although their underlying
      mechanisms are not yet fully understood. Acetylcholine and sodium nitroprusside
      iontophoresis, despite their wide use as specific tests of endothelium-dependent
      and -independent function, respectively, show limitations. The influence of the
      skin site, recording conditions, and the way of expressing data are also
      reviewed. Finally, we focus on promising tools such as laser speckle contrast
      imaging.

PMID- 21883641
TI  - Male breast cancer: management and follow-up recommendations.
AB  - National Comprehensive Cancer Network (NCCN) guidelines for female breast cancer
      treatment and surveillance are well established, but similar guidelines on male
      breast cancers are less recognized. As an NCCN institution, our objective was to
      examine practice patterns and follow-up for male breast cancer compared to
      established guidelines for female patients. After Institutional Review Board
      approval, a prospective breast database from 1990 to 2009 was queried for male
      patients. Medical records were examined for clinico-pathological factors and
      follow-up. The 5-year survival rates with 95% confidence intervals were estimated
      using Kaplan-Meier method and Greenwood formula. Of the 19,084 patients in the
      database, 73 (0.4%) were male patients; 62 had complete data. One patient had
      bilateral synchronous breast cancer. The median age was 68.8 years (range 29-85
      years). The mean/median invasive tumor size was 2.2/1.6 cm (range 0.0-10.0 cm).
      All cases had mastectomy (29 with axillary node dissection, 23 with sentinel
      lymph node biopsy only, 11 with sentinel node biopsy followed by completion
      axillary dissection). Lymph node involvement occurred in 25/63 (39.7%). Based on
      NCCN guidelines, chemotherapy, hormonal therapy, and radiation are indicated in
      34 cases, 62 cases, and 14 cases, respectively. Only 20/34 (59%) received
      chemotherapy, 51/62 (82%) received hormonal therapy, and 10/14 (71%) received
      post-mastectomy radiation. Median follow-up was 26.2 months (range: 1.6-230.9
      months). The 5-year survival estimates for node positive and negative diseases
      were 68.5% and 87.5%, respectively (p = 0.3). Despite the rarity of male breast
      cancer, treatment options based on current female breast tumors produce
      comparable results to female breast cancer. Increased awareness and a national
      registry for patients could help improve outcomes and tailor treatment
      recommendations to the male variant.

PMID- 21883642
TI  - Microvascular dysfunction: a potential mechanism in the pathogenesis of obesity
      associated insulin resistance and hypertension.
AB  - The intertwined epidemics of obesity and related disorders such as hypertension,
      insulin resistance, type 2 diabetes, and subsequent cardiovascular disease pose a
      major public health challenge. To meet this challenge, we must understand the
      interplay between adipose tissue and the vasculature. Microvascular dysfunction
      is important not only in the development of obesity-related target-organ damage
      but also in the development of cardiovascular risk factors such as hypertension
      and insulin resistance. The present review examines the role of microvascular
      dysfunction as an explanation for the associations among obesity, hypertension,
      and impaired insulin-mediated glucose disposal. We also discuss communicative
      pathways from adipose tissue to the microcirculation.

PMID- 21883643
TI  - Cold-induced urticaria after fractional carbon dioxide laser resurfacing of the
      face.

PMID- 21883644
TI  - Enhanced effect of platelet-rich plasma containing a new carrier on hair growth.
AB  - BACKGROUND: Treatments for alopecia are in high demand, but not all are safe and
      reliable. Dalteparin and protamine microparticles (D/P MPs) can effectively carry
      growth factors (GFs) in platelet-rich plasma (PRP). OBJECTIVE: To identify the
      effects of PRP-containing D/P MPs (PRP&D/P MPs) on hair growth. METHODS &
      MATERIALS: Participants were 26 volunteers with thin hair who received five local
      treatments of 3 mL of PRP&D/P MPs (13 participants) or PRP and saline (control,
      13 participants) at 2- to 3-week intervals and were evaluated for 12 weeks.
      Injected areas comprised frontal or parietal sites with lanugo-like hair.
      Experimental and control areas were photographed. Consenting participants
      underwent biopsies for histologic examination. RESULTS: D/P MPs bind to various
      GFs contained in PRP. Significant differences were seen in hair cross-section but
      not in hair numbers in PRP and PRP&D/P MP injections. The addition of D/P MPs to
      PRP resulted in significant stimulation in hair cross-section. Microscopic
      findings showed thickened epithelium, proliferation of collagen fibers and
      fibroblasts, and increased vessels around follicles. CONCLUSION: PRP&D/P MPs and
      PRP facilitated hair growth but D/P MPs provided additional hair growth. The
      authors have indicated no significant interest with commercial supporters.

PMID- 21883645
TI  - Z-plasty innovations in vertical lip reconstructions.
AB  - BACKGROUND: Although the Z-plasty has been used on the lips in various
      applications, its novel utility in improving classic vertical (radial) lip
      reconstruction has not been described previously. OBJECTIVE: To demonstrate the
      advantages of Z-plasties in vertical lip reconstruction, to explore six distinct
      causes of lip deformities that arise during reconstructive surgery and how those
      complications can be avoided by employing traditional Z-plasties or a new
      modification we term the "sliding Z-plasty," and to provide an entirely original
      first-time analysis of the geometry and physical dynamics of lip reconstruction.
      MATERIALS AND METHODS: We explored the planning and execution of lip
      reconstruction using traditional Z-plasties and a new sliding Z-plasty
      modification. This analysis uses case reports, original illustrations, and an in
      depth discussion of the spatial dynamics of lip reconstruction. CONCLUSION:
      Traditional or sliding Z-plasties can improve the final outcome of vertical lip
      reconstruction while avoiding or mitigating six distinct potential complications
      associated with classic repairs.

PMID- 21883646
TI  - Prevention of thyroidectomy scars in Asian adults using a 532-nm potassium
      titanyl phosphate laser.
AB  - BACKGROUND: Prediction of whether postoperative wound healing will result in a
      hypertrophic scar or keloid is difficult. Diverse treatment options have been
      developed in an effort to prevent excessive scar formation. OBJECTIVE: To
      evaluate the efficacy and safety of a 532-nm potassium titanyl phosphate (KTP)
      laser in the prevention of scar formation after total thyroidectomy. MATERIALS
      AND METHODS: Twenty-eight individuals with Fitzpatrick skin types IV and V and
      linear surgical suture lines after total thyroidectomy by the same surgeon were
      enrolled. Twenty participants were treated using a 532-nm KTP laser two times at
      2-week intervals. Eight participants were assigned to the control group. The
      Vancouver Scar Scale (VSS), global assessment score (GAS), and participants'
      subjective satisfaction were used to determine the effect of scar prevention.
      These results were compared with those of the control group. RESULTS: The average
      VSS score was remarkably lower in the KTP laser treatment group. Average GASs
      indicated better cosmetic outcomes in the treatment group. Participant
      satisfaction was also higher in the treatment group. No significant side effects
      were observed during follow-up. CONCLUSION: A 532-nm KTP laser can be used safely
      and efficiently on Asian skin to reduce scar formation after thyroidectomy. The
      authors have indicated no significant interest with commercial supporters.

PMID- 21883647
TI  - Twenty years of clinical experience with a new modality of vascular-targeted
      photodynamic therapy for port wine stains.
AB  - BACKGROUND: Port wine stains (PWS) are congenital capillary malformations of the
      skin and are difficult to treat without scarring. Since January 1991, our group
      has performed a new modality of vascular-targeted photodynamic therapy (PDT) for
      PWS treatment. OBJECTIVE: To summarize our clinical experiences with vascular
      targeted PDT for PWS at Chinese PLA General Hospital. METHODS AND MATERIALS: Our
      group has collected and reviewed retrospective clinical research data of vascular
      targeted PDT for treating PWS since January 1991. RESULTS: Clinical studies
      showed that vascular-targeted PDT is an effective treatment for all types of PWS.
      Repetitive treatment sessions were usually needed to obtain a better cosmetic
      effect. No recurrence was seen in patients followed up for longer than 19 years.
      There were no significant side effects or adverse reactions. CONCLUSION: This new
      PDT is an effective, safe, and noninvasive modality with no recurrence for PWS,
      although the protocol for PDT requires further optimization.

PMID- 21883648
TI  - A double-blind, randomized study comparing pure chromated glycerin with chromated
      glycerin with 1% lidocaine and epinephrine for sclerotherapy of telangiectasias
      and reticular veins.
AB  - BACKGROUND: Chromated glycerin (CG) is an effective, although painful, sclerosing
      agent for telangiectasias and reticular leg veins treatment. OBJECTIVE: To
      determine pain level and relative efficacy of pure or one-third lidocaine
      epinephrine 1% mixed chromated glycerin in a prospective randomized double-blind
      trial. METHOD: Patients presenting with telangiectasias and reticular leg veins
      on the lateral aspect of the thigh (C(1A) or (S) E(P) A(S) P(N1) ) were
      randomized to receive pure CG or CG mixed with one-third lidocaine-epinephrine 1%
      (CGX) treatment. Lower limb photographs were taken before and after treatment and
      analyzed by blinded expert reviewers for efficacy assessment (visual vein
      disappearance). Patients' pain and satisfaction were assessed using visual
      analogue scales. RESULTS: Data from 102 of 110 randomized patients could be
      evaluated. Patient pain scores were significantly higher when pure CG was used
      than with CGX (p<.001). Patient satisfaction with treatment outcome was similar
      in the two groups. Objective visual assessment of vessel disappearance revealed
      no significant difference between the two agents (p=.07). CONCLUSION: Addition of
      lidocaine-epinephrine 1% to CG, in a ratio of one-third, significantly reduces
      sclerotherapy pain without affecting efficacy when treating telangiectasias and
      reticular leg veins.

PMID- 21883649
TI  - Endovenous 808-nm diode laser occlusion of perforating veins and varicose
      collaterals: a prospective study of 482 limbs.
AB  - BACKGROUND: Endovenous laser ablation (EVLA) was performed in the treatment of
      great and small saphenous veins (GSVs, SSVs), perforating veins (PVs), and
      varicose collaterals (VCs). OBJECTIVE To verify the outcome in PVs and VCs.
      MATERIALS AND METHODS: Four hundred eighty-two limbs of 306 patients were
      studied. EVLA was performed on 167 GSVs, 52 SSVs, and 534 PVs of 303 limbs and on
      VCs of 467 limbs; 133 GSVs were stripped, 300 of saphenofemoral junctions (SFJs)
      and 45 saphenopopliteal junctions (SPJs) were interrupted. Limbs were selected
      using duplex ultrasound examination and photographs; PVs-VCs diameter (<4 mm) and
      VC length were measured. EVLA was performed using a 808-nm diode laser, 0.6-mm
      fibers, continuous emission, 4 to 10 W, and 10 to 20 J/cm. Follow-up on 467 limbs
      occurred over a mean 27.5 months (range 3 months to 6 years); 98 limbs were
      followed up for longer than 4 years. RESULTS: Operating time range from 10 to 30
      minutes per limb. Blood vaporization, thrombosis, fibrosis, and atrophy prevailed
      in PVs and in the large VCs (>4 mm) and massive coagulation in the smaller (<4
      mm). High rate of occlusion was seen, with different rates of patent PV-VC mainly
      in diameter >6 mm. Thirty-nine out of 511 patent PVs (7.6%) and 96 out of 778 VCs
      (12-13%) were re-treated using EVLA or foam sclerotherapy. Minor complications
      occurred in 88 of the 778 (11%). CONCLUSIONS: EVLA of PVs and VCs is effective
      and faster than surgery in 2- to 6-mm PVs and VCs using an 808-nm diode laser.

PMID- 21883650
TI  - Fractional rejuvenation using a novel bipolar radiofrequency system in Asian
      skin.
AB  - BACKGROUND: Fractional photothermolysis (FP) constitutes an effective modality of
      skin resurfacing by delivering thermal energy into multiple arrays of microscopic
      treatment zones. Radiofrequency (RF) can induce volumetric heating of dermis
      depending on electrical properties of target tissue. OBJECTIVES: To evaluate the
      efficacy and safety of a novel bipolar RF-based fractional device for the
      treatment of photoaged Asian faces. METHODS: Twenty-six Korean women (mean age
      56, skin phototype III-IV) received three consecutive fractional RF treatments at
      4- to 6-week intervals. Outcome assessments included standardized photography
      physician evaluation of fine lines, pores, smoothness and tightness, brightness,
      and overall appearance; degree of elastosis; subjective improvement scale; and
      patient satisfaction. RESULTS: Fractional RF treatments produced moderate (26
      50%) and incremental improvements in each category of physician evaluation. In
      particular, degree of smoothness and tightness, brightness, and overall
      appearance improved significantly 6 weeks after the third session from before the
      third session. The degree of elastosis was 5.46 at baseline, which decreased
      significantly to 4.05 at 6-week follow-up. Patient self-assessment paralleled the
      physician assessment. Adverse events were limited to mild erythema, swelling, and
      scabs, which usually shed 3.9 days after treatment. CONCLUSION: Fractional
      bipolar RF treatment is an effective treatment for facial photodamage in Asians,
      with a favorable safety profile.

PMID- 21883654
TI  - Bone tissue in esophagus: an osteogenic metastasis.

PMID- 21883655
TI  - Thoracic endovascular aortic repair for aortic complications after esophagectomy
      for cancer: report of three cases.
AB  - Aortic complications after esophageal cancer surgery are rare and usually fatal.
      Here, we report three patients who underwent thoracic endovascular aortic repair
      (TEVAR) for aortic complications after esophagectomy for cancer. In the first
      case, aortic rupture was caused by pyothorax due to residual tumor after
      esophagectomy. In the second case, aortic rupture was caused by pyothorax due to
      anastomotic leakage. In the third case, a pseudoaneurysm was caused by surgical
      injury during esophagectomy. TEVAR was safe and effective for severe aortic
      complications when graft infection was avoided. The first case died of sepsis on
      the 84th postoperative day, and the other two cases have survived 4 years and 2
      years to date.

PMID- 21883656
TI  - Randomized clinical trial of laparoscopic anterior 180 degrees  partial versus
      360 degrees  Nissen fundoplication: 5-year results.
AB  - Anterior partial fundoplication (AF) has been popularized by a lower risk of
      mechanical side effects. The question then emerges whether anterior partial wrap
      has a similar antireflux effect with Nissen fundoplication (NF). We therefore
      conducted a randomized study to compare the long-term outcome of anterior
      fundoplication with NF. One hundred patients who enrolled in the trial from May
      2003 to March 2005 were randomized to laparoscopic AF or laparoscopic NF.
      Endoscopy, pH monitoring, manometry, a detailed questionnaire, and a visual
      analog symptom score were completed preoperative at 6, 12, 24, and 60 months
      after surgical procedures. The postoperative adverse effects such as dysphagia
      and flatulence were compared between the two groups. Revision surgery or
      maintenance proton pump inhibitor therapy was defined as failure. Fifty
      procedures were performed in each group. The outcome at 5 years follow-up was
      determined for 96 patients (96%; 49 patients in the AF group and 47 in the NF
      group). Three patients (3%) died of unrelated causes during follow-up, and one
      patient changed address. Both fundoplications were found to provide good control
      of reflux-related symptoms in most of the patients. For 96 patients followed up
      more than 5 years, gastroesophageal reflux symptoms were well controlled in 81
      patients (84.38%); the mean DeMeester scores in the AF group decreased from
      106.89 +/- 14.12 to 12.67 +/- 3.14 and in the NF group from 109.51 +/- 17.98 to
      10.81 +/- 2.65, and the esophagitis was ameliorated visibly. Moreover, there were
      significantly fewer patients in the AF group who complained of flatulence.
      Compared with NF, anterior 180 degrees  partial fundoplication is an effective
      treatment of gastroesophageal reflux and associates with fewer postoperative
      adverse effects.

PMID- 21883657
TI  - Programmed cell death 4 nuclear loss and miR-21 or activated Akt overexpression
      in esophageal squamous cell carcinogenesis.
AB  - The programmed cell death 4 (PDCD4) tumor suppressor is down-regulated in several
      malignancies, and the (subcellular) expression of its protein product is
      modulated by both oncomiR miR-21 and protein kinase B (Akt). PDCD4 and activated
      Akt (phosphorylated Akt [pAkt]) expression were assessed immunohistochemically in
      53 tissue samples obtained from 25 endoscopic esophageal mucosal resections
      performed for squamous intraepithelial neoplasia (IEN) or squamous intramucosal
      carcinoma (IM-SSC). In total, 33 IEN (low-grade = 15; high-grade = 15) and 20 IM
      SSC specimens were considered; 50 additional tissue samples of histologically
      proven normal esophageal mucosa were considered as normal controls. To further
      validate the results achieved, miR-21 expression (as assessed by quantitative
      real-time polymerase chain reaction and in situ hybridization) was tested in
      another series of 15 normal esophageal tissue samples, 15 high-grade IEN, and 15
      IM-SCCs. Normal suprabasal squamous epithelial layers consistently featured
      strong PDCD4 nuclear immunostaining, which was significantly lower (P < 0.001) in
      IEN (both low-and high-grade) and in IM-SSC. Conversely, pAkt and miR-21
      expression was significantly up-regulated in the whole spectrum of
      preneoplastic/neoplastic lesions considered. PDCD4 down-regulation, as assessed
      by immunohistochemistry, is a reliable biomarker of early-stage squamous cell
      esophageal neoplasia, providing additional information in the histological
      assessment of these lesions.

PMID- 21883658
TI  - Fluid overload deteriorate chylothorax: evaluation in a canine model.
AB  - No conservative treatments for chylothorax have yet been established, and
      surgical ligation of the thoracic duct is required in many cases. In the present
      study, we investigated the management of body fluid in a canine chylothorax
      model. Twelve beagle dogs were divided evenly into three groups: A, B, and C.
      Under general anesthesia, the thoracic duct was cut and opened, and the amount of
      lymph fluid leakage was measured. Intravenous extracellular fluid infusion was
      started at 5mL/kg/h for the first 2h, and then between 2 and 4h, the infusion
      rate was increased to 10 mL/kg/h in group A and to 20mL/kg/h in group B. During
      the first 2h after cutting the thoracic duct, the mean lymph fluid leakage rates
      in groups A, B, and C were 0.466, 0.635, and 0.575 mL/kg/h, respectively. The
      rates of leakage did not differ significantly among the groups. Between 2 and 4h,
      the mean rates of leakage were 0.750, 1.43, and 0.544mL/kg/h, respectively, being
      significantly higher in groups A and B than in group C. The amount of lymph fluid
      ascending the thoracic duct correlates with the amount of intravenous fluid
      infusion. For the management of chylothorax, it is important to avoid fluid
      overload.

PMID- 21883659
TI  - Resuscitation strategies from bupivacaine-induced cardiac arrest.
AB  - OBJECTIVES: Local anesthetic (LA) intoxication with cardiovascular arrest is a
      potential fatal complication of regional anesthesia. Lipid resuscitation has been
      recommended for the treatment of LA-induced cardiac arrest. Aim of the study was
      to compare four different rescue regimens using epinephrine and/or lipid emulsion
      and vasopressin to treat cardiac arrest caused by bupivacaine intoxication.
      METHODS: Twenty-eight piglets were randomized into four groups (4 * 7),
      anesthetized with sevoflurane, intubated, and ventilated. Bupivacaine was infused
      with a syringe driver via central venous catheter at a rate of 1 mg.kg(-1).min(
      1) until circulatory arrest. Bupivacaine infusion and sevoflurane were then
      stopped, chest compression was started, and the pigs were ventilated with 100%
      oxygen. After 1 min, epinephrine 10 MUg.kg(-1) (group 1), Intralipid((r)) 20% 4
      ml.kg(-1) (group 2), epinephrine 10 MUg.kg(-1) + Intralipid((r)) 4 ml.kg(-1)
      (group 3) or 2 IU vasopressin + Intralipid((r)) 4 ml.kg(-1) (group 4) were
      administered. Secondary epinephrine doses were given after 5 min if required.
      RESULTS: Survival was 71%, 29%, 86%, and 57% in groups 1, 2, 3, and 4. Return of
      spontaneous circulation was regained only by initial administration of
      epinephrine alone or in combination with Intralipid((r)). Piglets receiving the
      combination therapy survived without further epinephrine support. In contrast, in
      groups 2 and 4, return of spontaneous circulation was only achieved after
      secondary epinephrine rescue. CONCLUSIONS: In cardiac arrest caused by
      bupivacaine intoxication, first-line rescue with epinephrine and epinephrine +
      Intralipid((r)) was more effective with regard to survival than Intralipid((r))
      alone and vasopressin + Intralipid((r)) in this pig model.

PMID- 21883660
TI  - Streptococcus pneumoniae exposure is associated with human metapneumovirus
      seroconversion and increased susceptibility to in vitro HMPV infection.
AB  - It remains largely unknown which factors determine the clinical outcome of human
      metapneumovirus (HMPV) infections. The aim of the present study was to analyse
      whether exposure to bacterial pathogens can influence HMPV infections. From 57
      children, serum samples and colonization data for Haemophilus influenzae,
      Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pneumoniae were
      collected at 1.5, 6, 14 and 24 months of age. Seroconversion rates to HMPV were
      determined and related to bacterial carriage. Frequent nasopharyngeal carriage
      (>=2 times in the first 2 years of life) of S. pneumoniae, but not of the other
      three pathogens, was associated with increased seroconversion rates of infants to
      HMPV at the age of 2 years (frequently vs. less exposed, 93% vs. 59%; p <0.05).
      Subsequently, the susceptibility of well-differentiated normal human bronchial
      epithelial cells (wd-NHBE) pre-incubated with bacterial pathogens to in vitro
      HMPV infection was evaluated. Pre-incubation of wd-NHBE with S. pneumoniae
      resulted in increased susceptibility to infection with HMPV-enhanced green
      fluorescent protein (EGFP), as determined by enumeration of EGFP-positive cells.
      This was not the case for cells pre-incubated with H. influenzae, M. catarrhalis
      on S. aureus. We conclude that exposure to S. pneumoniae can modulate HMPV
      infection.

PMID- 21883661
TI  - Phage lysin as a substitute for antibiotics to detect Mycobacterium tuberculosis
      from sputum samples with the BACTEC MGIT 960 system.
AB  - Phage lysin was evaluated as a substitute for antibiotics in sputum samples
      processed by a modified Petroff's method for the detection of Mycobacterium
      tuberculosis with the MGIT 960 system. One hundred and fifty sputum samples were
      processed, inoculated onto two slopes of Lowenstein-Jensen medium, and divided in
      to two aliquots of 0.5 mL each. One aliquot was added to 7 mL of MGIT medium
      containing polymyxin B, amphotericin B, nalidixic acid, trimethoprim and
      azlocillin (PANTA) (MGIT-PANTA) and the other was added to 7 mL of MGIT medium
      containing 0.8 mL of lysin (MGIT-Lysin). The samples were randomized and
      incubated at 37 degrees C in the MGIT 960 system. The sensitivity and specificity
      of MGIT-Lysin were 97% and 88%, respectively, as compared with MGIT-PANTA. The
      average times to detection with MGIT-Lysin and MGIT-PANTA were 9.3 and 8.6 days,
      respectively. The rate of contamination with MGIT-PANTA and MGIT-Lysin were 16%
      and 7.3%, respectively. Phage lysin can be substituted for antibiotics in
      processed sputum samples for the detection of M. tuberculosis.

PMID- 21883662
TI  - Species identification of Aspergillus, Fusarium and Mucorales with direct surface
      analysis by matrix-assisted laser desorption ionization time-of-flight mass
      spectrometry.
AB  - Accurate species discrimination of filamentous fungi is essential, because some
      species have specific antifungal susceptibility patterns, and misidentification
      may result in inappropriate therapy. We evaluated matrix-assisted laser
      desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) for species
      identification through direct surface analysis of the fungal culture. By use of
      culture collection strains representing 55 species of Aspergillus, Fusarium and
      Mucorales, a reference database was established for MALDI-TOF MS-based species
      identification according to the manufacturer's recommendations for microflex
      measurements and MALDI BioTyper 2.0 software. The profiles of young and mature
      colonies were analysed for each of the reference strains, and species-specific
      spectral fingerprints were obtained. To evaluate the database, 103 blind-coded
      fungal isolates collected in the routine clinical microbiology laboratory were
      tested. As a reference method for species designation, multilocus sequencing was
      used. Eighty-five isolates were unequivocally identified to the species level
      (>=99% sequence similarity); 18 isolates producing ambiguous results at this
      threshold were initially rated as identified to the genus level only. Further
      molecular analysis definitively assigned these isolates to the species
      Aspergillus oryzae (17 isolates) and Aspergillus flavus (one isolate), concordant
      with the MALDI-TOF MS results. Excluding nine isolates that belong to the fungal
      species not included in our reference database, 91 (96.8%) of 94 isolates were
      identified by MALDI-TOF MS to the species level, in agreement with the results of
      the reference method; three isolates were identified to the genus level. In
      conclusion, MALDI-TOF MS is suitable for the routine identification of
      filamentous fungi in a medical microbiology laboratory.

PMID- 21883663
TI  - Membrane permeability, a pivotal function involved in antibiotic resistance and
      virulence in Enterobacter aerogenes clinical isolates.
AB  - Imipenem-susceptible E. aerogenes isolates exhibiting extended spectrum beta
      lactamases, target mutations and a basal efflux expression, were identified in
      five patients. After imipenem treatment, imipenem-intermediate susceptible (IMI
      I) or resistant (IMI-R) isolates emerged in these patients. Alteration in porin
      synthesis and increase in efflux expression were observed in the IMI-I isolates
      whereas complete loss of the porins, LPS alteration and efflux overexpression
      were observed in the IMI-R isolates. Bacterial virulence of the strains was
      investigated by the Caenorhabditis elegans model. The IMI-R isolates were shown
      to be significantly less virulent than the IMI-susceptible or IMI-I isolates. The
      pleiotropic membrane alteration and its associated fitness burden exhibited by E.
      aerogenes isolates influence their antibiotic resistance and their virulence
      behaviour. These findings highlight the balance between the low permeability
      related resistance and virulence and their relationships with the treatment of
      resistant pathogens.

PMID- 21883664
TI  - Value of (1-3)-beta-d-glucan, Candida mannan and Candida DNA detection in the
      diagnosis of candidaemia.
AB  - This study determined the value of (1,3)-beta-d-glucan (BDG), Candida mannan (MN)
      and Candida species-specific DNA as surrogates for diagnosis of candidaemia.
      Thirty-nine patients yielding Candida species in blood cultures were investigated
      for presence of BDG, MN and Candida species-specific DNA in serum samples. The
      Candida spp. bloodstream isolates included C. albicans (n = 16), C. tropicalis (n
      = 10), C. parapsilosis (n = 7), C. glabrata (n = 3) and C. dubliniensis (n = 3).
      Positivity of the three markers was as follows: Candida DNA for corresponding
      Candida species, 100%; BDG, 87%; MN, 59%. Despite varying sensitivities of these
      biomarkers, they provided a useful adjunct to the diagnosis of candidaemia.

PMID- 21883665
TI  - Malaria vaccines and the new malaria agenda.
AB  - The development of an effective malaria vaccine has taken many decades, but there
      is now a good chance that the first malaria vaccine will be licensed within the
      next few years. However, this vaccine (RTS,S) will not be fully effective, and
      more efficacious, second-generation vaccines will be needed. Good progress is
      being made in the development of potential vaccines directed at each of the three
      main stages of the parasite's life cycle, with a variety of different approaches,
      but many challenges remain, e.g. overcoming the problem of polymorphism in many
      key parasite antigens. It is likely vaccines that are effective enough to block
      transmission, and thus contribute to increasing drives towards malaria
      elimination, will need to contain antigens from different stages of the
      parasite's life cycle.

PMID- 21883666
TI  - Characteristics and prognosis in patients with prosthetic vascular graft
      infection: a prospective observational cohort study.
AB  - Prosthetic vascular graft infection (PVGI) is a devastating complication, with a
      mortality rate of up to 75%, which is especially caused by aortic graft
      infection. The purpose of this study was to evaluate factors associated with in
      hospital mortality of patients with definite graft infection, and with long-term
      outcome. We reviewed medical records of 85 patients treated for PVGIs defined by
      positive bacterial culture of intraoperative specimens or blood samples, and/or
      clinical, biological and radiological signs of infection. In-hospital patient
      mortality was defined as any death occurring during the initial treatment of the
      graft infection. Cure was defined as the absence of evidence of relapsing
      infection during long-term follow-up (>=1 year). Eighty-five patients (54 aortic
      and 31 limb graft infections) treated by surgical debridement and removal of the
      infected prosthesis (n=41), surgical debridement without removal of prosthesis
      (n=34) or antimicrobial treatment without surgery (n=10) were studied. The only
      microbiological difference observed between patients with early (occurring within
      4 months after surgery) vs. late PVGI and between those with aortic vs. limb PVGI
      was the incidence of PVGI caused by Staphylococcus aureus, which was greater in
      patients with limb PVGI. Overall cure was observed in 93.2% of 59 patients with a
      follow-up of a minimum of 1 year. Overall in-hospital mortality was 16.5% (n=14).
      Two variables were independently associated with mortality: age >70 years (OR
      9.1, 95% CI 1.83-45.43, p 0.007) and aortic graft infection (OR 5.6, 95% CI 1.1
      28.7, p 0.037).

PMID- 21883667
TI  - Genetic diversity of carbapenem-hydrolysing beta-lactamases in Acinetobacter
      baumannii from Romanian hospitals.
AB  - Thirteen carbapenem-resistant Acinetobacter baumannii isolates, collected in
      Romania during 2009-2010, were investigated to identify the mechanism(s)
      responsible for carbapenem resistance. Genotyping was performed by pulsed-field
      gel electrophoresis, multiplex PCR sequence typing and multilocus sequence
      typing. Eleven non-clonally related isolates harboured the bla(OXA-23) gene on
      their chromosome within a Tn2008 transposon structure. The two remaining isolates
      harboured a bla(OXA-58) gene that was either plasmid or chromosome borne. Two
      isolates co-expressed OXA-23 together with the extended-spectrum beta-lactamase
      PER-1. This study constitutes the first report of OXA-58 and OXA-23-producing A.
      baumannii isolates in Romania.

PMID- 21883668
TI  - Borrelia hispanica in Ornithodoros erraticus, Portugal.
AB  - Tick-borne relapsing fever (TBRF) is a spirochetal infection caused by the genus
      Borrelia. The disease is distributed in the Old and New World with many different
      species reported. In Europe, TBRF is caused by B. hispanica transmitted to man by
      Ornithodoros erraticus, a soft tick usually found in old premises to shelter pig
      herds. In Portugal, the first human case of TBRF was reported in 1942 but since
      the beginning of the 1960s, the disease has rarely been described and seems to
      either have disappeared or have been undiagnosed. Therefore, in 2009 a survey was
      undertaken to evaluate the presence of the tick in this type of premises and to
      evaluate its role as a reservoir of Borrelia. The work was carried out where the
      ticks were previously reported in the Alentejo and Algarve regions. Of 63 pigpens
      surveyed, O. erraticus was collected from 19% (n = 12) of these pigpens using
      CO(2) traps. To evaluate potential Borrelia hosts, both pigs (n = 25) and small
      rodents (n = 10) inhabiting these pigpens were surveyed for Borrelia presence, by
      whole blood PCR and/or tissue culture, respectively. All results for pigs and
      rodents were negative for the presence of B. hispanica. PCR assays targeting the
      16S rRNA gene and intergenic spacer region of Borrelia were used. Sequence
      analysis of the positive samples confirmed the presence of B. hispanica in 2.2%
      (n = 5) of ticks from a pigpen in Alentejo. These results confirm natural, but
      albeit low, persistence of this agent in Portugal.

PMID- 21883669
TI  - Invasive group A streptococcal infections in adults, France (2006-2010).
AB  - Severe invasive group A streptococcal diseases have re-emerged during the past 10
      20 years. In order to provide a better insight into the current epidemiological
      situation in France, we analysed the questionnaires regarding all invasive
      strains received at the National Reference Center for Streptococci (CNR-Strep)
      between 2006 and 2010 from patients aged >= 18 and characterized them by emm
      typing, spe gene detection and antibiotic resistance. Among the 1542 invasive GAS
      strains studied, 78% (n=1206) were from blood cultures, and a streptococcal toxic
      shock syndrome (STSS) was described in 22% (n=340) of cases, mainly associated
      with necrotizing fasciitis (NF) and pleuro-pulmonary infections (p<0.001). The in
      hospital fatality rate was 15%. A total of 83 different emm types were recovered
      but the three predominant emm types, representing almost 60% of the isolates,
      were emm1 (24%), emm28 (17%) and emm89 (15%). The preponderance of each emm type
      varied according to the year, with a significant constant increase of emm28
      strains, whereas emm1 strains, representing approximately 32% of GAS invasive
      isolates in 2007 and 2008, dropped to <15% in 2010 (p<0.001). The distribution of
      phage-associated superantigen genes (speA, speC and ssa) was linked to certain
      emm types. Between 2006 and 2010, the percentage that was macrolide-resistant
      decreased from 11% to 5%, confirming the trend observed in 2007. Fortunately,
      emm1 strains associated with the most life-threatening clinical manifestations
      remain susceptible to all anti-streptococcal antibiotics.

PMID- 21883670
TI  - Initial Pseudomonas aeruginosa infection in patients with cystic fibrosis:
      characteristics of eradicated and persistent isolates.
AB  - Despite intensive eradication therapy, some CF patients with early Pseudomonas
      aeruginosa infection rapidly develop a chronic infection. To elucidate factors
      associated with this persistence, bacterial characteristics of early P.
      aeruginosa isolates were analysed that were either eradicated rapidly or
      persisted despite multiple antimicrobial treatments. Eighty-six early infection
      episodes were studied. First P. aeruginosa isolates from patients with
      eradication (36) or persistent infection (16) were included; isolates from
      patients with intermittent infection (34) were omitted from the study. Virulence
      assays, antimicrobial resistance, cytotoxicity and mutation frequencies were
      analysed in vitro. P. aeruginosa was genotyped by SNP-array. Transcriptomic
      profiles of two eradicated and two persistent strains were compared. Nineteen per
      cent of patients developed persistent infection; 42% achieved eradication.
      Secretion of virulence factors and mutation frequencies were highly variable
      among both eradicated and persistent isolates and were not different between the
      groups. Cytotoxicity was present in 57% of eradicated vs. 100% of persistent
      isolates (p <0.01). None of the isolates were resistant to antibiotics. The
      isolates were genotypically highly diverse. Multivariate analysis showed that in
      vitro determined bacterial characteristics could not predict persistence after
      first P. aeruginosa infection. Preliminary transcriptomic data showed increased
      expression of some genes related to a metabolic pathway. The early onset of
      chronic infection was not associated with (in vitro determined) bacterial
      characteristics only. Although the persistent isolates were more often cytotoxic,
      for the individual patient it was not possible to predict the risk of persistence
      based on bacterial characteristics. Unknown factors such as host-pathogen and
      pathogen-pathogen interactions should be further explored.

PMID- 21883671
TI  - Invasive group B streptococcal infections in adults, France (2007-2010).
AB  - Group B streptococcus (GBS) has emerged as an important cause of invasive
      infection in adults. Here, we report the clinical and microbiological
      characteristics of 401 non-redundant GBS strains causing adult invasive
      infections collected during a 4-year period (2007-2010). Bacteraemia without
      focus (43.4%) and bone and joint infections (18.7%) were the main clinical
      manifestations. The distribution of capsular polysaccharide (CPS) type showed
      that types Ia, III, and V accounted for 71.8% of all strains. Resistance to
      erythromycin increased from 20.2% in 2007 to 35.3% in 2010, and was mainly
      associated with CPS type V harbouring the erm(B) resistant determinant.

PMID- 21883672
TI  - Assessment of markers of glycaemic control in diabetic patients with chronic
      kidney disease using continuous glucose monitoring.
AB  - AIM: Due to altered red blood cell survival and erythropoietin therapy glycated
      haemoglobin (HbA1c) may not accurately reflect long-term glycaemic control in
      patients with diabetes and chronic kidney disease (CKD). Glycated albumin (GA)
      and fructosamine are alternative markers of glycaemia. The aim of this study was
      to investigate the accuracy of HbA1c, GA and fructosamine as indicators of
      glycaemic control using continuous glucose monitoring. METHODS: HbA1c, GA and
      fructosamine concentrations were measured in 25 subjects with diabetic
      nephropathy (CKD stages 4 and 5 (estimated glomerular filtration rate <30 mL/min
      per 1.73 m(2) )) matched with 25 subjects with diabetes and no evidence of
      nephropathy. Simultaneous real-time glucose concentrations were monitored by
      continuous glucose monitoring over 48 h. RESULTS: GA correlated significantly to
      mean glucose concentrations in patients with and without CKD (r = 0.54 vs 0.49, P
      < 0.05). A similar relationship was observed with fructosamine relative to
      glucose. A poor correlation between HbA1c and glucose was observed with CKD (r =
      0.38, P = ns) but was significant in the non-CKD group (r = 0.66, P < 0.001). The
      GA/HbA1c ratio was significantly higher in diabetic patients with CKD compared
      with controls (2.5 +/- 0.4 vs 2.2 +/- 0.4, P < 0.05). HbA1c values were
      significantly lower in CKD patients, relative to non-CKD patients at comparable
      mean glucose concentrations. CONCLUSION: HbA1c significantly underestimates
      glycaemic control in patients with diabetes and CKD stages 4 and 5. In severe
      CKD, GA more accurately reflects glycaemic control compared with fructosamine and
      HbA1c and should be the preferred marker of glycaemic control.

PMID- 21883673
TI  - Blind peritoneal catheter placement with a Tenckhoff trocar by nephrologists: a
      single-center experience.
AB  - AIM: Blind peritoneal dialysis (PD) catheter instrumentation with a Tenckhoff
      trocar is performed without direct visualization of the peritoneum. This method
      requires the least equipment, it is safe and it can be performed mainly by
      nephrologists. We report here on our long-term experience with this method as
      performed by nephrologists. METHODS: We reviewed the medical records at Yeungnam
      University Hospital in Korea and identified all the patients who had undergone
      blind PD catheter instrumentation with a Tenckhoff trocar by nephrologists. Four
      hundred and three patients were enrolled. RESULTS: Early complications occurred
      in 7.7% (four patients with pericatheter bleeding, one patient with pleural
      leakage, two patients with migration, two patients with omental wrapping, three
      patients with exit site/tunnel infection and 19 patients with peritonitis). The
      late mechanical complications included eight cases of hernia, three cases of
      catheter extrusion, five cases of leakage, four cases of migration and five cases
      of omental wrapping. Exit site/tunnel infection and peritonitis occurred at a
      rate of 0.067 and 0.40 episodes/year, respectively. The intervention free
      survival rate was 84.5% at one year and 63.3% at 5 years. The catheter survival
      rate was 96.5% at one year and 83.6% at 5 years. CONCLUSION: This study provides
      evidence that blind PD catheter placement with a Tenckhoff trocar requires the
      least equipments, and it is easy to perform. Therefore, if the general anesthesia
      is impossible or equipment, such as fluoroscopy and laparoscopy, were not
      available, this method may be an alternative choice for PD catheter placement.

PMID- 21883674
TI  - Discrimination between COPD patients with and without alpha 1-antitrypsin
      deficiency using an electronic nose.
AB  - BACKGROUND AND OBJECTIVE: To compare the volatile organic compound patterns of
      patients with COPD with and without alpha 1-antitrypsin (AAT) deficiency using
      electronic nose technology. METHODS: Exhaled breath condensate and pure exhaled
      breath of patients with COPD with (n=10) and without (n=23) AAT deficiency and
      healthy controls (n=10) were analysed. The effect of human recombinant AAT on the
      volatile organic compound profile of 11 AAT-deficient patients was also examined.
      Exhaled breath condensate and pure exhaled breath were measured using the
      Cyranose 320. Smell prints were analysed by linear discriminant analysis (LDA)
      using Mahalanobis distance (MD) and cross-validation values (CVVs). RESULTS:
      Smell prints of patients with AAT-deficiency were different from those with COPD
      in exhaled breath condensate (LDA: P<0.0001, sensitivity of 1.00, specificity of
      1.00, CVV 82.0%, MD 2.37) and in pure exhaled breath (LDA: P<0.0001, sensitivity
      of 1.00, specificity of 1.00, CVV 58.3%, MD 2.27). Smell prints of AAT-deficient
      patients before and after human recombinant AAT augmentation were different (LDA:
      P=0.001, sensitivity of 1.00, specificity of 1.00, CVV 53.3%, MD 1.79).
      CONCLUSIONS: An electronic nose can detect differences in smell prints of COPD
      patients with and without AAT deficiency. Augmentation therapy changes the
      volatile organic compound pattern. The electronic nose may be helpful in the
      diagnosis of AAT deficiency.

PMID- 21883675
TI  - Weakness of expiratory muscles and pulmonary complications in malnourished
      patients undergoing upper abdominal surgery.
AB  - BACKGROUND AND OBJECTIVE: Malnutrition is prevalent in hospitalized patients and
      causes systemic damage including effects on the respiratory and immune systems,
      as well as predisposing to infection and increasing postoperative complications
      and mortality. This study aimed to assess the impact of malnutrition on the rate
      of postoperative pulmonary complications, respiratory muscle strength and chest
      wall expansion in patients undergoing elective upper abdominal surgery. METHODS:
      Seventy-five consecutive candidates for upper abdominal surgery (39 in the
      malnourished group (MNG) and 36 in the control group (CG)) were enrolled in this
      prospective controlled cohort study. All patients were evaluated for nutritional
      status, respiratory muscle strength, chest wall expansion and lung function
      before surgery. Postoperative pulmonary complications (pneumonia,
      tracheobronchitis, atelectasis and acute respiratory failure) before discharge
      from hospital were also evaluated. RESULTS: The MNG showed expiratory muscle
      weakness (MNG 65 +/- 24 vs CG 82 +/- 22 cm H(2) O; P < 0.001) and decreased chest
      wall expansion (P < 0.001), whereas inspiratory muscle strength and lung function
      were preserved (P > 0.05). The MNG also had a higher incidence of postoperative
      pulmonary complications compared with the CG (31% and 11%, respectively; P =
      0.05). In addition, expiratory muscle weakness was correlated with BMI in the MNG
      (r = 0.43; P < 0.01). The association between malnutrition and expiratory muscle
      weakness increased the likelihood of postoperative pulmonary complications after
      upper abdominal surgery (P = 0.02). CONCLUSIONS: These results show that
      malnutrition is associated with weakness of the expiratory muscles, decreased
      chest wall expansion and increased incidence of pulmonary complications in
      patients undergoing elective upper abdominal surgery.

PMID- 21883676
TI  - Changes in lung composition and regional perfusion and tissue distribution in
      patients with ARDS.
AB  - BACKGROUND AND OBJECTIVE: ARDS is characterized by bilateral pulmonary
      infiltrates and refractory hypoxemia attributed to V/Q mismatch. We used dynamic
      CT to characterize changes in lung composition, regional perfusion and tissue
      distribution in patients with ARDS in comparison with healthy subjects. METHODS:
      The Fick principle was applied to serial attenuation measurements constructed
      from sequential CT images acquired during the passage of a bolus of iodinated
      contrast medium in healthy subjects (n=3) and patients with ARDS (n=11).
      Perfusion was calculated by the Mullani-Gould method and mapped throughout both
      lungs. Gradients of perfusion and tissue density against vertical height were
      constructed. RESULTS: In comparison with normal individuals, the tissue component
      of lungs from patients with ARDS was significantly increased (P<0.05). Blood
      fraction was unchanged. There was a discernable gradient in tissue density from
      non dependent to dependent regions in the patients with ARDS that was
      significantly different from controls. The proportion of perfusion applied to
      consolidated areas (i.e. shunt) correlated significantly (P<0.05) with the
      severity of hypoxaemia. CONCLUSIONS: In patients with ARDS there are changes in
      both lung composition and the distribution of tissue and perfusion that may
      account in part for the physiological changes that define the syndrome.

PMID- 21883677
TI  - ATP-binding cassette B1 gene polymorphisms, mRNA expression and chemosensitivity
      to paclitaxel in non-small cell lung cancer cells.
AB  - BACKGROUND AND OBJECTIVE: The adenosine triphosphate (ATP)-binding cassette, sub
      family B, member 1 (ABCB1) gene encodes P-glycoprotein (Pgp), which plays an
      important role in drug disposition by limiting intracellular uptake of
      paclitaxel. ABCB1 gene polymorphisms may alter the expression and function of
      Pgp, thereby influencing the response to chemotherapy. A panel of 17 non-small
      cell lung cancer (NSCLC) cell lines was used to investigate whether alterations
      in the ABCB1 gene or its mRNA expression correlated with in vitro
      chemosensitivity to paclitaxel. METHODS: Polymorphisms in the ABCB1 gene were
      evaluated by direct sequencing. mRNA expression levels were assessed by
      quantitative real-time reverse transcription PCR. In vitro chemosensitivity to
      paclitaxel was expressed as half-maximal inhibitory concentration values, using a
      tetrazolium (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-based
      colorimetric assay. RESULTS: The variant allele frequencies for four ABCB1 gene
      polymorphisms were 14.71% for 2677G>T/A, 32.35% for 2734T>C, 23.53% for 3396C>T
      and 76.47% for 3435C>T. There was a significant positive correlation between
      ABCB1 mRNA expression and half-maximal inhibitory concentration values for
      paclitaxel (r=0.5322, P=0.0279). None of the four ABCB1 gene polymorphisms were
      associated with paclitaxel chemosensitivity or ABCB1 mRNA expression in the 17
      cell lines. CONCLUSIONS: These in vitro results suggest that high ABCB1 mRNA
      expression may be a predictive biomarker for poor chemosensitivity to paclitaxel.
      The panel of NSCLC cell lines may provide clues and indications for establishing
      clinically useful relationships between a given polymorphism or level of gene
      expression and chemosensitivity to an anti-cancer agent.

PMID- 21883678
TI  - Potential benefits of early continuous positive pressure ventilation in patients
      with rapidly progressive interstitial pneumonia.
AB  - BACKGROUND AND OBJECTIVE: Rapidly progressive interstitial pneumonia (RPIP),
      including acute exacerbations of interstitial pneumonia, is associated with high
      rates of mortality. The present study was performed to examine the effects of
      respiratory management using non-invasive ventilation (NIV) in patients with RPIP
      and to assess the prognostic factors for survival. METHODS: BiPAP Vision was used
      for NIV. Clinical data and information on NIV were retrospectively obtained from
      patient records. Survival at 30 days was evaluated, and biomarkers were measured
      after initiation of NIV. RESULTS: Thirty-eight patients who had been admitted
      with RPIP and treated by NIV were included in the study. The ratio of PaO(2) to
      fraction of inspired oxygen at initiation of NIV was higher in survivors than in
      non-survivors (P = 0.0054). The mean duration to initiation of NIV after
      admission was significantly shorter in survivors than in non-survivors (P =
      0.0006). Serum Krebs von den Lungen-6 (KL-6) and LDH levels at the start of NIV
      were higher in non-survivors than in survivors (KL-6, P = 0.022; LDH, P = 0.044).
      Bivariate logistic regression analysis showed that early intervention with NIV
      was a significant predictor of survival at 30 days. In addition, the ratio of
      PaO(2) to fraction of inspired oxygen and both LDH and KL-6 levels at initiation
      of NIV were significant predictors of survival. CONCLUSIONS: Early intervention
      with NIV, mainly continuous positive pressure ventilation, is beneficial for the
      management of patients with RPIP. A randomized controlled study in a large
      population is needed to confirm the value of early NIV.

PMID- 21883679
TI  - Airway dimensions and pulmonary function in chronic obstructive pulmonary disease
      and bronchial asthma.
AB  - BACKGROUND AND OBJECTIVE: COPD and bronchial asthma are chronic airway diseases
      with a different pathogenesis. Comparisons of differences in airway calibre by
      bronchial generation between these diseases and their importance to pulmonary
      function have not been fully studied. We investigated airway calibre and wall
      thickness in relation to pulmonary function in patients with asthma, COPD, asthma
      plus emphysema and normal subjects using CT. METHODS: Sixty-three asthmatic
      patients, 46 COPD, 23 patients with asthma plus emphysema and 61 control subjects
      were studied cross-sectionally. We used a software with curved multiplanar
      reconstruction to measure airway dimensions from 3rd- to 6th-generation bronchi
      of the right lower posterior bronchus. RESULTS: Patients with COPD had increased
      wall thickness, but the airway was not narrow from the 3rd-(subsegmental) to 6th
      generation bronchi. Mean bronchial inner diameter (Di) of 3rd- to 6th-generation
      bronchi in patients with asthma or asthma plus emphysema was smaller than that of
      COPD patients and normal subjects. Airway luminal area (Ai) of 5th-generation
      bronchi most closely correlated with pulmonary function in patients with stable
      asthma. Although Di was similar in patients with asthma and asthma plus
      emphysema, the Ai of 6th-generation bronchi correlated significantly with
      pulmonary function in patients with asthma plus emphysema. CONCLUSIONS: Airway
      calibre in asthma may be smaller than in COPD. Airflow limitations correlated
      more closely with peripheral Ai in patients with asthma plus emphysema than in
      patients with asthma alone.

PMID- 21883680
TI  - When pleural potassium exceeds 5.0 mEq/L, high pleural adenosine deaminase levels
      do not necessarily indicate tuberculous pleuritis.
AB  - BACKGROUND AND OBJECTIVE: The aim of this study was to determine whether high
      levels of pleural adenosine deaminase (pADA) are predictive for tuberculosis when
      pleural effusions do not satisfy the criteria for lymphocytic effusions or show
      neutrophil predominance. METHODS: This was a retrospective observational study of
      147 consecutive patients with exudative pleural effusions that were diagnosed by
      analysis of fluid samples during a 3-year period from 1 April 2007 to 31 March
      2010. Multiple linear correlation tests were used to assess clinical variables as
      possible predictors of high pADA levels. RESULTS: High pleural LDH (pLDH) and
      pleural potassium (pK) levels were associated with high pADA levels (P < 0.0001).
      Although there was a linear correlation between pLDH and pADA levels in patients
      with parapneumonic effusions (PPE) (n = 75), tubercular effusions (n = 21),
      malignant effusions (n = 41) and miscellaneous effusions (n = 10), a significant
      linear correlation between pK and pADA levels was observed only in patients with
      PPE (rho = 0.525, P < 0.0001). When the cut-off value for pK was set at 5.0
      mEq/L, pADA levels were >50 IU/L and pK levels were >5.0 mEq/L in only one
      patient (5%) in the tuberculosis group (n = 21) and 15 patients (12%, all with
      PPE) in the non-tuberculosis group (n = 126). CONCLUSIONS: When pK levels exceed
      5.0 mEq/L, high pADA levels do not necessarily indicate the presence of
      tuberculous pleuritis.

PMID- 21883681
TI  - The role of non-invasive home mechanical ventilation in patients with chronic
      obstructive pulmonary disease requiring prolonged weaning.
AB  - BACKGROUND AND OBJECTIVE: Patients with COPD who require prolonged weaning from
      invasive mechanical ventilation show poor long-term survival. Whether non
      invasive home mechanical ventilation (HMV) has a beneficial effect after
      prolonged weaning has not yet been clearly determined. METHODS: Patients with
      COPD who required prolonged weaning and were admitted to a specialized weaning
      centre between January 2002 and February 2008 were enrolled in the study. Long
      term survival and prognostic factors, including the role of non-invasive HMV,
      were evaluated. RESULTS: Of 117 patients (87 men, 30 women; mean age 69.5+/-9.5
      years) included in the study, weaning from invasive ventilation was achieved in
      82 patients (70.1%). Successful weaning was associated with better survival 1
      year after discharge from hospital (hazard ratio (HR) 2.24, 95% CI: 1.16-4.31;
      P=0.016). Among the 82 patients who were successfully weaned, non-invasive HMV
      was initiated in 39 (47.6%) due to persistent chronic ventilatory failure.
      Initiation of HMV was associated with a higher rate of survival to 1 year as
      compared with patients who did not receive ventilatory support (84.2% vs 54.3%;
      HR 3.68, 95% CI: 1.43-9.43; P=0.007). In addition, younger age and higher PaO2,
      haemoglobin concentration and haematocrit at discharge were associated with
      better survival. In an adjusted multivariate analysis, initiation of non-invasive
      HMV after successful weaning remained an independent prognostic factor for
      survival to 1 year (HR 3.63, 95% CI: 1.23-10.75; P=0.019). CONCLUSIONS: These
      findings suggest that based on the potential for improvement in long-term
      survival, non-invasive HMV should be considered in patients with severe COPD and
      persistent chronic hypercapnic respiratory failure after prolonged weaning.

PMID- 21883682
TI  - Short of breath, short of benefit: important considerations for the
      rehabilitation of IPF patients.

PMID- 21883684
TI  - Does fever phobia cross borders? The case of Japan.
AB  - BACKGROUND: Undue parental fear of fever in children was termed "fever phobia" by
      Schmitt following a survey in the USA in 1980. In 2000, Crocetti et al. conducted
      the same survey and concluded that fever phobia existed even 20 years later. In
      this study, we explore differences in fever phobia between these two US
      populations and a Japanese sample, and determine whether parents of a single
      child or those whose child was previously hospitalized or had a febrile seizure
      report greater anxiety about fever. METHODS: A questionnaire was distributed to
      parents of children who visited a pediatric outpatient clinic in Juntendo
      University Nerima Hospital between 19 and 30 November 2007. RESULTS: Data was
      obtained from 211 parents who agreed to participate in the study. Compared with
      much smaller proportions reported in the two previous studies, 62% of caregivers
      considered a temperature below 37.8 degrees C to be a fever, although less than
      half of parents reported that they were "very worried" about fever. Over 90%
      identified doctors and nurses as their primary information source. In contrast to
      7% of parents in the US studies, almost no parents reported that temperatures
      could rise to or above 43.3 degrees C if fever was left untreated; however, 63%
      of parents stated that they would visit a hospital. CONCLUSIONS: Fever phobia
      exists on both sides of the border, and while caregivers in Japan appear to have
      a more accurate understanding of fever, they are more likely to rely on health
      care professionals to manage the condition.

PMID- 21883683
TI  - Vitamin B12 treatment reduces mononuclear DNA damage.
AB  - BACKGROUND: DNA damage effects of vitamin B(12) deficiency were performed in
      vitro and in adults. METHODS: The study group included 32 children (13 girls, 19
      boys) with vitamin B(12) deficiency (mean age 44 +/- 58 months) and their 27
      mothers (mean age 30.4 +/- 5.3 years). The control group contained 30 healthy
      children and 25 mothers. DNA strand breaks in peripheral blood mononuclear
      leukocytes were assayed by single-cell alkaline gel electrophoresis (comet assay)
      before and 8 days after the first injection of vitamin B(12). RESULTS: Mean DNA
      damage scores in children with vitamin B(12) deficiency and their mothers were
      significantly higher before treatment than those after treatment. The DNA damage
      scores of children after treatment were still significantly higher than controls.
      There were significant negative correlations between the children and their
      mothers in terms of vitamin B(12) levels and DNA damage scores (r = 0.3, P= 0.02;
      r = 0.58, P= 0.002, respectively). There were correlations between the children's
      and their mothers' DNA damage and the severity of vitamin B(12) deficiency,
      suggesting that the children and their mothers may play a role in the scarcity of
      nutritional vitamin B(12). CONCLUSION: DNA damage is increased in children with
      vitamin B(12) deficiency and in their mothers. DNA damage scores were
      significantly improved through vitamin B(12) therapy 8 days after the first
      injection, however, they were still significantly higher than those of controls.

PMID- 21883685
TI  - Congenital heart disease in a Chinese hospital: pre- and postnatal detection,
      incidence, clinical characteristics and outcomes.
AB  - BACKGROUND: The pre- and postnatal detection rate, incidence, clinical
      characteristics and outcomes of congenital heart disease (CHD) have been studied
      in developed countries for many years, but rarely have large-scale studies been
      reported in Chinese populations. The aim of the present study was to investigate
      the pre- and postnatal detection rates, incidence, clinical characteristics and
      outcomes of CHD in a Chinese hospital in order to improve the future screening
      and treatment of CHD. METHODS: Fetuses without risk factors for CHD were screened
      using basic cardiac ultrasound examination (BCUE). Fetuses with suspected cardiac
      malformation revealed by BCUE and fetuses with risk factors were screened using
      extended cardiac ultrasound examination. Outcomes recorded from fetal, neonatal
      and postmortem records over 4 years (2006-2009) included: therapeutic termination
      of pregnancy, spontaneous abortions or stillbirths, deaths at birth or in the
      neonatal period (before 28 days of age), and rate of birth and clinical
      characteristics of newborns. RESULTS: A total of 34,071 fetuses were screened for
      CHD during a period of 4 years, of which 173 fetuses were screened for CHD using
      BCUE and 301 fetuses were screened using extended cardiac ultrasound examination.
      The incidence of fetal CHD increased from 1.1% in 2006 to 2.4% in 2009 (P <
      0.05), yielding an overall incidence of 1.5% (523/34,071). Of the fetuses with
      CHD, 48.2% (252/523) died before 28 days of age (including intra-uterine death
      and termination of pregnancy), 51.8% (271/523) lived more than 28 days and the
      incidence of live newborns with CHD was 0.80% (271/34071). CONCLUSIONS: The
      prevalence of CHD was quite common in this Chinese hospital. Detailed profiles of
      CHD suggest that, while training programs in obstetric screening at this hospital
      were beneficial, prenatal intervention, treatment and care of fetal CHD were
      inefficient and should be strengthened in China.

PMID- 21883687
TI  - Ictal electrocardiographic changes in children presenting with seizures.
AB  - BACKGROUND: The aim of this study was to determine electrocardiographic changes
      in children during seizures. METHODS: We assessed heart rate changes, RR
      intervals and QT changes during 47 seizures in children. Consecutive QT and RR
      intervals were measured for 60 s before the seizures, during the seizures and 60
      s after the seizures during video electroencephalography monitoring. RESULTS:
      There were 47 seizures in 18 patients. Five patients had generalized seizures and
      13 patients had focal seizures. Twelve patients were male. The mean age during
      monitoring was 10.1 years (range 4 months-19 years). Ictal tachycardia was seen
      in every seizure. No ictal bradycardia was noted. There was only one dropped beat
      in a patient. The mean ictal heart-rate-corrected QT (QTc) interval was
      significantly higher than the postictal measurements (P= 0.005). Mean ictal QTc
      variation tended to increase during seizures and then decreased below the pre
      ictal measurements in the postictal period. However these changes were
      statistically insignificant (P > 0.05). RR variance was significantly decreased
      during seizures compared to the postictal period and the standard deviation of
      the RR intervals was significantly decreased in the ictal period compared to the
      pre-ictal period (P= 0.014 and P= 0.001, respectively). CONCLUSION: Tachycardia
      is the main finding in seizures in children. Ictal bradycardia and cardiac
      arrhythmias are very rare despite being more frequent in adults with seizures.

PMID- 21883686
TI  - Individualized long-term enzyme therapy for Gaucher disease type 1 in Slovenia.
AB  - BACKGROUND: Gaucher disease type 1 (GD1) was the first lysosomal storage disorder
      for which an effective enzyme replacement therapy was developed. We describe the
      management of eight GD1 patients in Slovenia who were diagnosed between the ages
      of 2 and 15 years. METHODS: Patients were individually assessed to establish
      initial enzyme doses and monitored frequently to determine the effects of long
      term enzyme dose regimens. Outcomes up to 10 years after long-term treatment are
      described by changes in the Zimran severity score index, chitotriosidase and acid
      phosphatase levels, and after 2001, bone parameters (DEXA bone mineral density
      scores and the MRI bone marrow burden score). RESULTS: Following the initiation
      of enzyme therapy with individualized dose regimens (range 25-56 U/kg/14 days)
      and followed by a gradual reduction of doses (range 12-35 U/kg/14 days) during
      long-term maintenance, disease status improved in all patients as measured by the
      Zimran severity score index (from a mean of 11.25 [median 11.5] before therapy to
      a mean of 4.12 [median 3.5] at last report). Anemia and leucopenia resolved in
      all patients, chitotriosidase and acid phosphatase levels decreased in all
      patients (and by over 75% in six patients) within 1 year of treatment. Bone
      marrow burden scores improved in all monitored patients and DXA scores improved
      in six of seven monitored patients. CONCLUSIONS: We conclude that enzyme therapy
      with relatively low, individualized dose regimens is well-tolerated and effective
      in children and young adults with GD1 disease, who are regularly monitored for
      changes in disease status.

PMID- 21883688
TI  - Serum and cerebrospinal fluid S100B, neuron-specific enolase, and total tau
      protein in acute encephalopathy with biphasic seizures and late reduced
      diffusion: a diagnostic validity.
AB  - BACKGROUND: Acute encephalopathy with biphasic seizures and late reduced
      diffusion (AESD) is characterized clinically by biphasic seizures and late
      magnetic resonance imaging abnormalities, such as reduced subcortical diffusion
      from day 3 onwards, often accompanied with some neurological sequelae. In the
      early stages of the disease, AESD closely resembles its far more prevalent and
      relatively benign counterpart, febrile seizure (FS). METHODS: We measured and
      compared the serum or cerebrospinal fluid (CSF) levels of S100B, neuron-specific
      enolase (NSE), and total tau protein in 43 patients with FS and 18 patients with
      AESD, at any point during the disease. To assess early diagnostic validity, we
      compared these biomarkers in 43 FS and eight AESD patients, with whom the day 0-2
      samples were available. We used the receiver-operator characteristic curve to
      evaluate the diagnostic values of these markers. RESULTS: The levels of all
      biomarkers were significantly higher in AESD than FS patients. When only day 0-2
      samples from AESD patients were used, the levels of all the measured biomarkers,
      except serum NSE, were still significantly higher in patients with AESD than in
      FS, suggesting that AESD could damage astrocytes, neurons, and axons, even in the
      early stages of the disease. According to the receiver-operator characteristic
      curve analyses, CSF S100B (cut-off value, 100 pg/mL) and CSF total tau protein
      (cut-off value, 100 pg/mL) were better predictors of AESD than other biomarkers.
      CONCLUSION: The combination of CSF S100B and CSF total tau protein resulted in a
      positive predictive value of AESD 83.3%, which could be helpful for early
      diagnosis, facilitating early therapeutic interventions.

PMID- 21883689
TI  - Quality of life in mothers of children with obstetrical brachial plexus palsy.
AB  - BACKGROUND: The aim of this study was to explore impairment in quality of life
      (QOL) of the mothers who were primarily responsible for taking care of children
      with obstetrical brachial plexus palsy (OBPP) and to state its association with
      the age, sex and functional status of the child with OBPP. METHODS: Ninety-three
      mothers of children with OBPP and 88 mothers of children without any health
      problems were included in the study. Children's demographic characteristics were
      recorded and the functional status of the upper extremity was determined with the
      active movement scale. The QOL of the mothers was assessed with the Turkish
      version of the Nottingham Health Profile (NHP). RESULTS: There were significant
      differences between mothers of children with OBPP and the control group in total,
      physical activity, energy expenditure, and pain score of the NHP. A decrease in
      energy expenditure and physical activity levels were found to be related to
      children's active movement scale results in elbow flexion and extension, and
      forearm supination. A statistically meaningful difference was found between
      mothers of children aged 0-2 and mothers of children aged 2-7 years in emotional
      reaction, social isolation and total score of NHP. CONCLUSIONS: The results of
      this study revealed that mothers of children with OBPP have poor QOL compared
      with mothers of healthy children. The limitation in elbow joint movements was
      found to be important for the mothers. The strongest impact of the illness is on
      the emotional reactions and social isolation of the mothers. Professionals
      involved in the care of children with OBPP should also help parents to cope with
      the burden of caregiving.

PMID- 21883690
TI  - Is bilirubin/albumin ratio correlated with unbound bilirubin concentration?
AB  - BACKGROUND: The American Academy of Pediatrics guidelines recommend that the
      total bilirubin (TB)/albumin (Alb) ratio (B/A ratio), instead of serum
      concentration of unbound bilirubin (UB), can be used with TB for determining
      treatment modality for jaundiced newborns >= 35 weeks of gestation. It is
      unknown, however, whether the B/A ratio is actually correlated with serum UB.
      METHODS: Four hundred and ninety-seven serum samples were obtained from 209
      newborns >= 35 weeks of gestation, who were admitted to Kobe University Hospital.
      Serum UB concentration was measured using the glucose oxidase-peroxidase method.
      Serum TB and Alb concentrations were measured on spectrophotometry. B/A ratios
      were calculated and were linearly compared with serum UB. Furthermore, the
      accuracy of the B/A ratio was evaluated. RESULTS: The B/A ratio was significantly
      correlated with serum UB concentration. A serum UB concentration of 0.6 ug/dL was
      in agreement with a B/A ratio of 0.5. For comparison of the number of newborns
      who had serum UB concentrations >= or <0.6 ug/dL and B/A ratios >= or <0.5, we
      found the following characteristics: the concordance rate between serum UB
      concentrations and the B/A ratio was 94%, sensitivity was 51%, and specificity
      was 99%. CONCLUSIONS: The B/A ratio is significantly correlated with serum UB
      concentration in newborns >= 35 weeks of gestation. The B/A ratio, however, is
      underestimated when serum UB concentrations are >0.6 ug/dL.

PMID- 21883691
TI  - Use of cefoperazone/sulbactam in neonates.
AB  - BACKGROUND: Neonates are at high risk for nosocomial infections due to multidrug
      resistant pathogens. The use of beta-lactamase inhibitors in combination with
      beta-lactam antibiotics broadens the antimicrobial spectrum.
      Cefoperazone/sulbactam is used in children but there are limited data on its
      usage in neonates. The purpose of the present study was therefore to evaluate the
      use of cefoperazone/sulbactam in the treatment of neonatal infections caused by
      multidrug-resistant pathogens. METHODS: The records of neonates who were
      hospitalized and who received cefoperazone/sulbactam were reviewed. RESULTS:
      There were 90 infants who received cefoperazone/sulbactam. A pathogen could be
      isolated in 41 (45.6%) of the infants. In total, 17.1% of isolated pathogens were
      resistant to cefoperazone/sulbactam. Side-effects were seen in four of the
      infants. Two infants had cholestasis, one infant had neutropenia and one had
      superinfection with candida. CONCLUSION: Cefoperazone/sulbactam can be used in
      the treatment of nosocomial infections caused by multidrug-resistant pathogens in
      neonates.

PMID- 21883692
TI  - Antitumor activity of type III interferon alone or in combination with type I
      interferon against human non-small cell lung cancer.
AB  - The antitumor activities of type III interferon (IFN) (interleukin [IL]-28 and IL
      29) and the combination of type III IFN and type I IFN (IFN-alpha) were evaluated
      using human non-small cell lung cancer (NSCLC). The expression of type III and
      type I receptor complexes was detected in NSCLC lines. IL-29 significantly
      inhibited the in vitro growth of a wide range of NSCLC lines in a dose-dependent
      fashion. To a lesser degree, IL-28A also displayed growth inhibitory activity.
      Antitumor activity of type III IFN is associated with cell cycle arrest at the G1
      phase and apoptosis. IL-29 upregulated cyclin-dependent kinase inhibitor
      p21Waf1/Cip1 in cells sensitive, but not insensitive, to antiproliferative
      activity, and knockdown of p21 with small interfering RNA largely attenuated the
      antiproliferative effect. Intratumoral and systemic administration of IL-29
      inhibited OBA-LK1 and LK-1, but not A549, tumor growth in severe combined
      immunodeficiency mice. Immunohistochemical analyses demonstrated marked
      upregulated p21 and downregulated Ki-67 expression in tumors treated with IL-29.
      The interferon combination of IL-29 and IFN-alpha displayed a more effective
      antiproliferative effect and a more intense p21 expression than each reagent
      alone in vitro. Furthermore, interferon combination therapy suppressed in vivo
      NSCLC growth more effectively than interferon monotherapy. These findings
      demonstrate that type III IFN can mediate direct antitumor activities via
      increased p21 expression and induction of apoptosis and cooperate with type I IFN
      to elicit more efficient direct antitumor activities, and suggest the possibility
      that type III IFN might improve the efficacy and reduce the side-effects of type
      I IFN cancer therapy.

PMID- 21883693
TI  - Body iron stores and breast cancer risk in female atomic bomb survivors.
AB  - Iron can be a potent pro-oxidant and, on this basis, elevated body iron may
      increase the risk of cancer. Although epidemiological evidence is mixed, there is
      overall support for this possibility. In addition, because of this same oxidative
      capacity, body iron levels may alter radiation sensitivity. In the present study,
      a nested case-control study of breast cancer was conducted in Japanese atomic
      bomb survivors. Stored serum samples from the Adult Health Study cohort were
      assayed for ferritin levels and joint statistical analyses were conducted of
      ferritin and radiation dose on the risk of breast cancer. Serum ferritin is the
      best feasible indicator of body iron levels in otherwise healthy people. A total
      of 107 cases and 212 controls were available for analysis. The relative risk (RR)
      of breast cancer for a 1 log unit increase in ferritin was 1.4 (95% confidence
      interval 1.1-1.8). This translates to an RR of 1.64 comparing high and low values
      of the interquartile range among controls (58 and 13.2 ng/mL, respectively). The
      results support the hypothesis that elevated body iron stores increase the risk
      of breast cancer. However, the study was inconclusive regarding the question of
      whether body iron alters radiation-induced breast cancer risk.

PMID- 21883694
TI  - miR-92 is a key oncogenic component of the miR-17-92 cluster in colon cancer.
AB  - MicroRNAs (miRNAs) belong to a class of endogenously expressed non-coding small
      RNAs that function primarily as gene regulators. Growing evidence suggests that
      miRNAs play a significant role in tumor development, making them potential
      biomarkers for cancer diagnosis and prognosis. The miR-17-92 cluster has emerged
      as an important locus, being highly overexpressed in several cancers in
      association with cancer development and progression. The miR-17-92 miRNA cluster
      generates a single polycistronic primary transcript that yields six mature
      miRNAs: miR-17, miR-18a, miR-19a, miR-20a, miR-19b, and miR-92a. In colon cancer
      development, the pathophysiologic roles of these transcripts and their targets
      are largely unknown. In the present study, we performed copy number analyses of
      the six miRNAs transcribed from the miR-17-92 cluster in colon tumor tissues. We
      determined that miR-92a was transcribed at higher levels than the other five
      miRNAs in both adenomas and carcinoma. In addition, miR-92a directly targeted the
      anti-apoptotic molecule BCL-2-interacting mediator of cell death (BIM) in colon
      cancer tissues. An anti-miR-92a antagomir induced apoptosis of colon cancer
      derived cell lines. These data indicate that miR-92a plays a pivotal role in the
      development of colorectal carcinoma.

PMID- 21883695
TI  - Antitumor effects of alpha-bisabolol against pancreatic cancer.
AB  - In the present study, we investigated whether alpha-bisabolol, a sesquiterpene
      alcohol present in essential oils derived from a variety of plants, has antitumor
      effects against pancreatic cancer. alpha-Bisabolol induced a decrease in cell
      proliferation and viability in pancreatic cancer cell lines (KLM1, KP4, Panc1,
      MIA Paca2), but not in pancreatic epithelial cells (ACBRI515). alpha-Bisabolol
      treatment induced apoptosis and suppressed Akt activation in pancreatic cancer
      cell lines. Furthermore, alpha-bisabolol treatment induced the overexpression of
      early growth response-1 (EGR1), whereas EGR1 siRNA decreased the alpha-bisabolol
      induced cell death of KLM1 cells. Tumor growth in both subcutaneous and
      peritoneal xenograft nude mouse models was significantly inhibited by
      intragastric administration of 1000 mg/kg of alpha-bisabolol, once a week for
      three weeks. The results indicate that alpha-bisabolol could be a novel
      therapeutic option for the treatment of pancreatic cancer.

PMID- 21883696
TI  - Identification of a claudin-4 and E-cadherin score to predict prognosis in breast
      cancer.
AB  - The elevated expression of claudins (CLDN) and E-cadherin (CDH-1) was found to
      correlate with poor prognostic features. Our aim was to perform a comprehensive
      analysis to assess their potential to predict prognosis in breast cancer. The
      expression of CLDN-1, -3-5, -7, -8, -10, -15, -18, and E-cadherin at the mRNA
      level was evaluated in correlation with survival in datasets containing
      expression measurements of 1809 breast cancer patients. The breast cancer tissues
      of 197 patients were evaluated with tissue microarray technique and
      immunohistochemical method for CLDN-1-5, -7, and E-cadherin protein expression.
      An additional validation set of 387 patients was used to test the accuracy of the
      resulting prognostic score. Based on the bioinformatic screening of publicly
      available datasets, the metagene of CLDN-3, -4, -7, and E-cadherin was shown to
      have the most powerful predictive power in the survival analyses. An
      immunohistochemical protein profile consisting of CLDN-2, -4, and E-cadherin was
      able to predict outcome in the most effective manner in the training set.
      Combining the overlapping members of the above two methods resulted in the
      claudin-4 and E-cadherin score (CURIO), which was able to accurately predict
      relapse-free survival in the validation cohort (P = 0.029). The multivariate
      analysis, including clinicopathological variables and the CURIO, showed that the
      latter kept its predictive power (P = 0.040). Furthermore, the CURIO was able to
      further refine prognosis, separating good versus poor prognosis subgroups in
      luminal A, luminal B, and triple-negative breast cancer intrinsic subtypes. In
      breast cancer, the CURIO provides additional prognostic information besides the
      routinely utilized diagnostic approaches and factors.

PMID- 21883697
TI  - Infection of human enteroendocrine cells with Chlamydia trachomatis: a possible
      model for pathogenesis in irritable bowel syndrome.
AB  - BACKGROUND: Irritable bowel syndrome (IBS) is a widespread gastrointestinal
      disorder of unknown etiology. Recently, our group detected chlamydial antigens in
      enteroendocrine cells (EEC) of jejunum biopsies from patients with IBS.
      Impairment of EEC secretion upon Chlamydia infection might lead to disturbances
      of gut functions. We have therefore studied the interaction between Chlamydia and
      EEC in vitro. METHODS: Two different human enteroendocrine cell lines were
      studied: LCC-18 from a neuroendocrine colonic tumour and CNDT2 from a small
      intestinal carcinoid. Cell lines were infected with C. trachomatis serovar LGV II
      strain 434. We used Penicillin G for inducing persistent infection. The
      ultrastructure of infected cells was studied using transmission electron
      microscopy and immunofluorescence and we used RT-PCR analysis for studying
      changes in gene expression at different stages of infection. KEY RESULTS: We
      found that both cell lines could be infected with C. trachomatis yielding
      productive infections and persistence could be induced using penicillin G.
      Immunofluorescence showed different cellular distributions of serotonin and
      chromogranin A in non-infected (cytoplasmatic distribution) compared with
      infected cells (serotonin and chromogranin mostly in chlamydial inclusions). In
      line with the microscopical findings, we found a significant down-regulation of
      the gene coding for the vesicular monoamine transporter (VMAT1) in infected
      compared with non-infected EEC (P<0.05). CONCLUSIONS & INFERENCES: Altered
      protein distributions together with down-regulation of VMAT1 suggest that
      chlamydial infection may influence vesicular transport. It is therefore possible
      that such an infection in vivo could lead to disturbances in the regulation of
      gut functions.

PMID- 21883698
TI  - A placebo-controlled trial of an oral capsaicin load in patients with functional
      dyspepsia.
AB  - BACKGROUND: The pathophysiology of functional dyspepsia is poorly understood.
      Visceral hypersensitivity may play a key role. We studied a previously validated
      test to assess chemical hypersensitivity in functional dyspepsia by applying an
      oral capsaicin load. METHODS: A total of 116 outpatients with upper
      gastrointestinal (GI) symptoms participated in this double-blind, placebo
      controlled trial of which 73 patients received a final diagnosis of functional
      dyspepsia. Patients swallowed a capsule containing 0.75 mg capsaicin or placebo.
      A graded questionnaire evaluated the severity of nine upper GI symptoms before
      and after capsule ingestion and an aggregate symptom score was calculated. A
      final score of >9 was considered as a positive test. KEY RESULTS: In functional
      dyspepsia, median perception scores were 10.8 (interquartile range: 4.5-18.8)
      after ingestion of capsaicin and 0.5 (0.0-2.5) after placebo (P < 0.001). Thirty
      seven functional dyspepsia patients (54%) had a positive test after capsaicin
      ingestion, whereas only four (11%) patients with upper GI symptoms but without
      functional dyspepsia were capsaicin positive [median perception score: 1.5 (0.0
      5.0)]. After placebo, symptom scores were low and not significantly different
      among patient groups (P > 0.05). Clinical characteristics, age, and gender
      distribution was similar in capsaicin positive and capsaicin negative functional
      dyspepsia patients (P > 0.05). The value of patient blinding was good.
      CONCLUSIONS & INFERENCES: Half of functional dyspepsia patients had chemical
      hypersensitivity, determined with an oral capsaicin load. Placebo response was
      negligible. The results of the capsaicin test were not associated with specific
      dyspepsia symptoms or Rome subgroups.

PMID- 21883699
TI  - Acid inhibits TRPV4-mediated Ca2+ influx in mouse esophageal epithelial cells.
AB  - BACKGROUND: The transient receptor potential vanilloid 4 (TRPV4), a thermo
      sensitive stretch-activated cation channel, is expressed in the skin stratified
      squamous epithelium, contributing to the acquisition of barrier function.
      Similarly, functional TRPV4 may be located in the stratified squamous epithelial
      lining of the esophagus, being involved in the pathogenesis of gastroesophageal
      reflux disease (GERD). Here we investigated the expression of TRPV4 in the mouse
      esophageal epithelium. METHODS: TRPV4 expression at the mRNA and protein levels
      was examined by reverse transcription-polymerase chain reaction (RT-PCR), in situ
      hybridization, and immunohistochemistry. A calcium imaging technique and ATP
      assay were used to evaluate the functionality of TRPV4 in freshly isolated
      esophageal epithelial cells. KEY RESULTS: Transcripts and proteins encoding TRPV4
      were colocalized in the basal and intermediate layers of the esophageal
      epithelium. Both 4alpha-phorbol 12,13- didecanoate (4alpha-PDD), a selective
      agonist for TRPV4, and hypo-osmolar solution (160 mOsm) elevated the
      intracellular calcium concentration ([Ca(2+) ](i) ) in a subset of the isolated
      cells (70%). These [Ca(2+) ](i) increases were potently inhibited by ruthenium
      red (RuR), a TRPV4 channel antagonist, and were suppressed by extracellular
      protons (pH 5.0). Finally, application of 4alpha-PDD evoked ATP release in
      primary esophageal epithelial cells. CONCLUSIONS & INFERENCES: Acid-sensitive
      TRPV4 channels were mainly expressed in the esophageal epithelial cells of the
      basal and intermediate layers. Direct exposure of TRPV4-expressing cells to
      gastric acid, as would occur in cases of GERD, could influence their cellular
      functions, possibly aggravating the disease state.

PMID- 21883700
TI  - Preferential activation of the vagal nodose nociceptive subtype by TRPA1 agonists
      in the guinea pig esophagus.
AB  - BACKGROUND: The TRPA1 receptor is directly activated by a wide range of chemicals
      including many endogenous molecules relevant for esophageal pathophysiology. We
      addressed the hypothesis that the TRPA1 agonists differentially activate
      esophageal nociceptive subtypes depending on their embryological source (neural
      crest or epibranchial placodes). METHODS: Single cell RT-PCR and whole cell patch
      clamp recordings were performed on the vagal neurons retrogradely labeled from
      the guinea pig esophagus. Extracellular recordings were made in the isolated
      innervated esophagus preparation ex vivo. KEY RESULTS: Single cell RT-PCR
      revealed that the majority of the nodose (placodes-derived) and jugular (neural
      crest-derived) TRPV1-positive esophageal nociceptors express TRPA1. Single fiber
      recording showed that the TRPA1 agonists allyl-isothiocyanate (AITC) and
      cinnamaldehyde were effective in inducing robust action potential discharge in
      the nerve terminals of nodose nociceptors, but had far less effect in jugular
      nociceptors (approximately fivefold less). Higher efficacy of the TRPA1 agonists
      to activate nodose nociceptors was confirmed in the isolated esophagus-labeled
      vagal neurons in the whole cell patch clamp studies. Similarly to neural crest
      derived vagal jugular nociceptors, the spinal DRG nociceptors that are also
      neural crest-derived were only modestly activated by allyl-isothiocyanate.
      CONCLUSIONS & INFERENCES: We conclude that the TRPA1 agonists are substantially
      more effective activators of the placodes-derived than the neural crest-derived
      esophageal nociceptors. Our data predict that in esophageal diseases the presence
      of endogenous TRPA1 activators will be preferentially signaled by the vagal
      nodose nociceptors.

PMID- 21883701
TI  - Regulation of basal LC20 phosphorylation by MYPT1 and CPI-17 in murine gastric
      antrum, gastric fundus, and proximal colon smooth muscles.
AB  - BACKGROUND: Myosin light chain kinase (MLCK) and myosin light chain phosphatase
      (MLCP) govern myosin light chain (LC20) phosphorylation and smooth muscle
      contraction. Rho kinase (ROK) inhibits MLCP, resulting in greater LC20
      phosphorylation and force generation at a given [Ca(2+) ](i) . Here, we
      investigate the role of ROK in regulating LC20 phosphorylation and spontaneous
      contractions of gastric fundus, gastric antrum, and proximal colon smooth
      muscles. METHODS: Protein and phosphorylation levels were determined by western
      blotting. The effects of Y27632, nicardipine, and GF109203X on phosphorylation
      levels and contraction were measured. KEY RESULTS: gamma-Actin expression is
      similar in all three smooth muscles. LC20 and pS19 are highest, but ROK1 and ROK2
      are lowest, in antrum and proximal colon smooth muscles. LZ +/- myosin
      phosphatase targeting subunit 1 (MYPT1), CPI-17, and pT696, pT853, and pT38 are
      highest in fundus and proximal colon smooth muscles. Myosin phosphatase-rho
      interacting protein (M-RIP) expression is lowest in fundus, and highest in antrum
      and proximal colon smooth muscles. Y27632 reduced pT853 in each smooth muscle,
      but reduced pT696 only in fundus smooth muscles. Nicardipine had no effect on
      pT38 in each smooth muscle, while GF109203X reduced pT38 in proximal colon and
      fundus smooth muscles. Y27632 or nicardipine reduced pS19 in proximal colon and
      fundus smooth muscles. Y27632 or nicardipine inhibited antrum and proximal colon
      smooth muscle spontaneous contractions, but only Y27632 reduced fundus smooth
      muscle tone. Zero external Ca(2+) relaxed each smooth muscle and abolished LC20
      phosphorylation. CONCLUSIONS & INFERENCES: Organ-specific mechanisms involving
      the MLCP interacting proteins LZ +/- MYPT1, M-RIP, and CPI-17 are critical to
      regulating basal LC20 phosphorylation in gastrointestinal smooth muscles.

PMID- 21883702
TI  - Association of bile acid receptor TGR5 variation and transit in health and lower
      functional gastrointestinal disorders.
AB  - BACKGROUND: The membrane bound bile acid (BA) receptor, TGR5, is located on
      myenteric, cholinergic and nitrergic neurons in colon and proximal small
      intestine. Our aim was to assess the association of genetic variation in TGR5 and
      small bowel transit (SBT) and colonic transit. METHODS: In 230 healthy controls
      and 414 patients with lower functional GI disorders [FGID: irritable bowel
      syndrome (IBS)-alternators (Alt) 84, IBS-constipation (IBS-C) 157, IBS-diarrhea
      (IBS-D) 173], we tested the association between TGR5 SNP rs11554825 (minor allele
      frequency 41%) with symptom phenotype (total cohort) and intermediate phenotype
      (SBT or colonic transit by radioscintigraphy) which was available in 213 people
      in this cohort. The association with symptom phenotype was assessed using
      logistic regression, while the association with colonic filling at 6 h (CF6), and
      colonic transit [geometric center (GC) at 24 h] was assessed using ancova, in
      each instance assuming a dominant genetic model. KEY RESULTS: There was no
      significant association with symptom phenotype. We observed a potential
      association of SNP rs11554825 with overall transit: CF6 (P = 0.061) and GC24 (P =
      0.083). The association of the SNP with CF6 in the IBS-D subgroup (P = 0.017)
      indicated the TC/CC subgroup had an average 50% faster SBT compared with the TT
      subgroup. In IBS-D patients, GC24 was not significantly associated with
      rs11554825 (TC/CC vs TT). CONCLUSIONS & INFERENCES: Variation in TGR5 may
      contribute to altered SBT and colonic transit in lower FGID. Further studies are
      required to characterize the potential role of BA receptor, TGR5, in the
      mechanism and treatment of bowel dysfunction in lower FGID.

PMID- 21883703
TI  - Postinfectious irritable bowel syndrome: follow-up of a patient cohort of
      confirmed cases of bacterial infection with Salmonella or Campylobacter.
AB  - BACKGROUND: Gastrointestinal infections have been proposed to predict subsequent
      irritable bowel syndrome (IBS) but large-scale infectious events are rare and
      long-term data are missing. METHODS: We identified 576 individuals with a
      Salmonella or Campylobacter infection between 2000 and 2009 that were followed by
      a short postal questionnaire asking for the presence of current symptoms in 2010.
      In case of agreement (n = 90), an extended postinfectious (PI)-IBS questionnaire
      was mailed including the Hospital Anxiety Depression Scale and the Patient Health
      Questionnaire. KEY RESULTS: A total of 189 patients reported back (36%); 98 had a
      Salmonella and 91 had a Campylobacter infection, of which 56 reported persistent
      symptoms (9.7% of the initial sample). Fifty-one patients returned the PI-IBS
      questionnaire. Of 48 patients with complete data, 15 reported no or mild symptoms
      of abdominal pain or discomfort while 17 had moderate and 16 severe symptoms.
      Twenty-two met Rome IBS criteria, 14 (29%) reported GI symptoms before the
      infection. Patients with moderate and/or severe PI-IBS symptoms were
      significantly more often females, were more often infected by Salmonella than by
      Campylobacter, had more severe symptoms during the initial infection, and had
      more often GI symptoms prior to the infection. They reported higher anxiety,
      depression, and somatisation scores, but were not different with respect to acute
      stool habits. CONCLUSIONS & INFERENCES: Nearly 10% of patients with an intestinal
      bacterial infection report postinfectious symptoms up to 10 years after the
      infectious event. They represent a clinically important population with high
      psychiatric comorbidity and somatic symptom burden.

PMID- 21883704
TI  - Retrospective analysis of differences in annual factor VIII utilization among
      haemophilia A patients.
AB  - Finding differences in drug utilization patterns within rare patient populations
      is challenging without access to a large sample. Our objective was to identify
      patient and treatment-related factors associated with differences in annual
      recombinant factor VIII (rFVIII) utilization in a large cohort of haemophilia A
      patients. This retrospective analysis utilized a large, US specialty pharmacy
      dispensing database from January 2006 to September 2009. Differences in median
      annual FVIII utilization (IU kg(-1) year(-1)) by age, severity, treatment
      regimen, rFVIII product type and health insurance plan were tested using non
      parametric statistics and regression analysis. A total of 1011 haemophilia A
      patients were included in the overall analysis. Severe haemophilia patients had
      higher median annual FVIII utilization than mild/moderate patients (P < 0.0001).
      Median annual FVIII utilization was also significantly different between
      treatment regimens (episodic = 1429 IU kg(-1) year(-1) vs. prophylaxis = 3993 IU
      kg(-1) year(-1) for severe patients, P < 0.0001). Children (0-12 years old),
      adolescents (13-18 years old) and adults (19+ years old) with severe haemophilia
      A receiving prophylaxis utilized 4588, 4082 and 3223 IU kg(-1) year(-1) (P <
      0.0001). After controlling for age, severity, treatment regimen and insurance
      type, regression analysis revealed B domain-deleted recombinant FVIII (BDD
      rFVIII) was associated with 33% higher FVIII consumption compared with full
      length recombinant FVIII (FL-rFVIII) (P = 0.0172). Similar results were also seen
      when matching BDD-rFVIII and FL-rFVIII patients. Health insurance type was not
      associated with annual FVIII utilization. As expected, age, severity and
      treatment regimen were significantly associated with FVIII utilization. After
      controlling for confounders, patients receiving FL-rFVIII prophylactically were
      associated with lower annual FVIII utilization compared with patients receiving
      BDD-rFVIII prophylactically.

PMID- 21883705
TI  - Computational and molecular approaches for predicting unreported causal missense
      mutations in Belgian patients with haemophilia A.
AB  - Haemophilia A (HA) is caused by widespread mutations in the factor VIII gene. The
      high spontaneous mutation rate of this gene means that roughly 40% of HA
      mutations are private. This study aimed to describe the approaches used to
      confirm private disease-causing mutations in a cohort of Belgian HA patients. We
      studied 148 unrelated HA families for the presence of intron 22 and intron 1
      inversion by Southern blotting and polymerase chain reaction (PCR). Multiplex
      ligation-dependent probe amplification (MLPA) assay was used to detect large
      genomic rearrangements. Detection of point mutations was performed by DNA
      sequencing. Predicting the causal impact of new non-synonymous changes was
      studied by two general strategies: (i) molecular approaches such as family
      cosegregation, evaluation of the implicated codon based on phylogenic separated
      species and absence of the mutation in the general Belgian population, and (ii)
      bioinformatics approaches to analyse the potential functional consequences of
      missense mutations. Among the 148 HA patients, in addition to common intron 22
      and intron 1 inversions as well as large deletions or duplications, 67 different
      point mutations were identified, of which 42 had been reported in the HAMSTeRS
      database, and 25 were novel including 10 null variants for which RNA analyses
      confirmed the causal effect of mutations located in a splice site consensus and
      15 missense mutations whose causality was demonstrated by molecular approaches
      and bioinformatics. This article reports several strategies to evaluate the
      deleterious consequences of unreported F8 substitutions in a large cohort of HA
      patients.

PMID- 21883706
TI  - Heterotopic ossification in quadratus femoris muscle in a haemophilic patient.

PMID- 21883707
TI  - MCP-1 and CCR2 gene variants in oral squamous cell carcinoma.
AB  - AIM: We aimed to investigate a possible association of the MCP-1 and CCR2
      polymorphisms with the risk of developing oral squamous cell carcinoma (OSCC).
      METHODS: MCP-1 A2518G and CCR2 V64I gene polymorphisms were performed by
      polymerase chain reaction and restriction fragment length polymorphism, in 129
      patients with OSCC and 140 healthy control subjects. RESULTS: Individuals who had
      G allele and GG genotype of MCP-1, and 64I allele and wt/64I genotype of CCR2 had
      increased risk for OSCC (P<0.05.) In contrast, individuals with CCR2 wt/wt
      genotype seem to be protected from OSCC (P < 0.01). Haplotype analysis revealed
      that MCP-1G: CCR2 64I haplotype frequencies were significantly higher in patients
      than those of controls (P = 0.001). CONCLUSIONS: We can suggest that the G allele
      of MCP-1 and 64I allele of CCR2 may be risk factors for OSCC.

PMID- 21883708
TI  - Myeloid-derived suppressor cells contribute to oral cancer progression in 4NQO
      treated mice.
AB  - OBJECTIVE: Abnormal myelopoiesis especially the expansion of myeloid-derived
      suppressor cells (MDSCs) is increasingly recognized as an important reason for
      the escape of tumor from immune surveillance. This study aims to investigate the
      role of this specific population of cells in oral cancer progression. MATERIALS
      AND METHODS: 4-Nitroquinoline 1-oxide (4NQO) was used to induce oral cancer in
      C57BL/6 mice. The tongue mucosa was examined by hematoxylin and eosin staining.
      The distribution of MDSCs in the spleen and peripheral blood and T cell subsets
      in the spleen was analyzed by flow cytometry. The expression of MDSCs in the
      tongue tissues was investigated by immunohistochemical staining, and the
      expression of arginase-1 (ARG-1) and NOS-2 in the tongue tissues was detected by
      real-time PCR. RESULTS:   We found that during tumor progression, significantly
      increased frequency of MDSCs was observed in the spleens and peripheral blood of
      4NQO-treated mice, and the frequency of MDSCs in the spleens was positively
      correlated with systemic CD3(+) CD8(+) T cells. Moreover, 4NQO-treated mice
      showed significantly higher MDSCs infiltration and ARG-1 mRNA level in the tumor
      site. CONCLUSIONS: Myeloid-derived suppressor cells contribute to oral tumor
      progression and represent a potential target for immunotherapy of oral cancer.

PMID- 21883709
TI  - Oral clefts and behavioral health of young children.
AB  - OBJECTIVES: This study examined the behavioral health of young children with oral
      clefts, and effects of satisfaction with facial appearance, cleft team care,
      number of cleft-related surgeries, and socioeconomic status (SES). SUBJECTS AND
      METHODS: The study included a population-based sample of 104 children aged 2-12
      years with isolated oral clefts from the state of Iowa. Behavior was evaluated
      with the Child Behavior Checklist or the Pediatric Behavior Scale 30, depending
      on age, compared with normative samples. RESULTS: Risks of behavioral problems
      were not significantly different from normative samples except for higher
      inattention/hyperactivity risks at age 6-12 years. Low satisfaction with facial
      appearance was associated with behavioral problems in all domains, except
      aggression. Team-care effects were not associated with behavioral problems.
      Number of cleft-related surgeries was associated with increased
      anxiety/depression and somatic symptom risks. Higher SES was associated with
      reduced inattention/hyperactivity, aggressive/oppositional behavior, and somatic
      symptoms. CONCLUSIONS: Most children with oral clefts may have similar behavioral
      health outcomes to unaffected children, except for increased
      inattention/hyperactivity risks at older ages. However, low satisfaction with
      facial appearance, increased exposure to surgeries, and lower SES may
      significantly increase behavioral problems. Also, the findings emphasize the need
      to study the representation of behavioral health professionals on cleft teams and
      access to behavioral health care.

PMID- 21883711
TI  - Observation of health technologies after their introduction into clinical
      practice: a systematic review on data collection instruments.
AB  - RATIONALE, AIMS AND OBJECTIVES: Early assessment of health technologies after
      they are covered by the health system is deemed crucial to promptly identify and
      analyse unforeseen problems that may arise when these are used in real world
      settings. This paper aims to describe the various instruments which could be used
      for collecting information intended for prospective observation of health
      technologies, so as to choose the specific instrument best suited to each
      context. METHODS: Systematic review of the medical literature aimed at retrieving
      general reference documents on data collection instruments for post-introduction
      observation of health technologies. A purpose-designed systematic bibliographic
      search was elaborated for the main three data collection instruments identified.
      RESULTS: The three instruments are briefly described along with the main results
      of the studies retrieved, in terms of the advantages, drawbacks and
      considerations to be borne in mind when it comes to use these tools in post
      introduction observation of new technologies. CONCLUSIONS: At present, the most
      appropriate data collection method for conducting post-introduction observation
      of new technologies is the use of prospective clinical registries. Electronic
      clinical records may replace clinical registries in the near future, but
      currently there are still many doubts as to the quality of the information
      retrieved.

PMID- 21883712
TI  - Cost analysis of adding pregabalin or gabapentin to the management of community
      treated patients with peripheral neuropathic pain.
AB  - OBJECTIVE: To compare the cost of adding either pregabalin or gabapentin to the
      management of community-treated patients with peripheral neuropathic pain (PNP).
      METHODS: A retrospective observational study was conducted using medical records
      from a Spanish health care provider claims database. Patients receiving health
      care for PNP, above 18 years and for which either pregabalin or gabapentin was
      initiated between 2006 and 2008 were included. Economic evaluation included
      health care resource utilization costs and costs due to sick leave. RESULTS: A
      total of 1163 patients with PNP were eligible for analysis: 764 were prescribed
      pregabalin and 399 gabapentin in addition to current pain therapy. Mean age was
      59.2 years and 62.2% were female. Concomitant use of analgesics was higher in the
      gabapentin cohort (3.2 vs. 2.7; P = 0.003), mainly due to non-steroidal anti
      inflammatory drugs (74.9% vs. 69.5%; P = 0.018) and opioids (27.7% vs. 17.9%; P =
      0.031). Adjusted total costs per patient was lower in pregabalin-treated patients
      (?2514 vs. ?3241; P = 0.003), due to less sick leave (?1067 vs. ?1633; P = 0.018)
      and lower health care costs (?1447 vs. ?1609; P = 0.004). The higher acquisition
      cost of pregabalin (?351 vs. ?191; P < 0.001) was largely compensated with lower
      costs in medical visits, physiotherapy, hospital stays and concomitant
      analgesics. CONCLUSIONS: In community-treated patients with PNP, total costs were
      considerably less for those patients initiated with pregabalin therapy than for
      those patients starting gabapentin add-on therapy. The relatively higher
      treatment acquisition cost of pregabalin was largely compensated by the overall
      lower costs for the other components of health care resources and sick leave,
      thus reducing the economic impact on the health care provider's budget and
      society.

PMID- 21883710
TI  - Antibiotic effects on bacterial profile in osteonecrosis of the jaw.
AB  - OBJECTIVE: Oral infection is considered to play a critical role in the
      pathogenesis of bisphosphonate-related osteonecrosis of the jaw (BRONJ), and
      antibiotic therapy has become a mainstay of BRONJ therapy. This study was aimed
      to investigate the effect of antibiotics on bacterial diversity in BRONJ tissues.
      MATERIALS AND METHODS: The bacterial profile from soft tissues associated with
      the BRONJ lesion was determined using 16S rRNA-based denaturing gradient gel
      electrophoresis (DGGE) and sequencing. Twenty BRONJ subjects classified as stage
      0-2 were enrolled in this study, and patient groups were divided into an
      antibiotic cohort (n=10) treated with systemic antibiotic and a non-antibiotic
      cohort (n=10) with no prior antibiotic therapy. RESULTS: The DGGE fingerprints
      indicated no significant differences in bacterial diversity of BRONJ tissue
      samples. Patients on antibiotics had higher relative abundance of phylum
      Firmicutes with bacterial species, Streptococcus intermedius, Lactobacillus
      gasseri, Mogibacterium timidum, and Solobacterium moorei, whereas patients
      without antibiotics had greater amounts of Parvimonas micra and Streptococcus
      anginosus. Thirty percent of bacterial populations were uncultured (yet-to be
      cultured) phylotypes. CONCLUSION: This study using limited sample size indicated
      that oral antibiotic therapy may have a limited efficacy on the bacterial
      population associated with BRONJ lesions.

PMID- 21883713
TI  - Effects of increased payment for ventilation tube insertion on decision making
      for paediatric otitis media with effusion.
AB  - OBJECTIVE: The National Health Insurance (NHI) in Taiwan raised the physician fee
      for myringotomy with ventilation tube insertion (VTI) from $61.5 to $117.6 in
      July 2004. This study aimed to evaluate if the increased payment affected the
      decision making of physicians. METHODS: This study is a retrospective analysis by
      using NHI databank in Taiwan. All children less than 12 years old who underwent
      VTI from 1 July 2003 to 30 June 2006 were included. Waiting time and case numbers
      before and after the increased VTI payment were compared. The waiting time
      between public and private hospitals was also examined. RESULTS: From the 7408
      cases evaluated, there was no difference in waiting time before and after the
      raise of VTI payment, and no difference within each year group. The case number
      of VTI increased significantly after the increase in VTI payment (P < 0.05). The
      waiting time of VTI performed in private hospitals was shorter than that in
      public hospitals (P = 0.0001). CONCLUSION: The waiting time of VTI for children
      with otitis media with effusion (OME) has not been shortened after the increase
      in VTI payment. Waiting time in private hospitals is shorter than that in public
      hospitals. Increased payment for VTI has no effect on the physicians' decision
      making regarding to waiting time for children with OME in Taiwan.

PMID- 21883714
TI  - Satisfaction after the transition between electronic health record systems at six
      ambulatory practices.
AB  - RATIONALE, AIMS AND OBJECTIVES: Early adopters of electronic health records
      (EHRs) are transitioning from older to newer EHRs to satisfy meaningful use
      requirements. Facilitators and barriers to satisfaction after transitioning are
      important to understand as provider satisfaction is linked with improvement in
      health care. METHOD: We conducted a cross-sectional survey of providers who
      transitioned from an older to a newer EHR at six academic, urban ambulatory
      medical practices. A novel survey was developed to assess: (1) satisfaction with
      the EHR implementation; (2) patterns of information technology use; (3) work
      perceptions; (4) methods for completing clinical tasks; and (5) demographic
      characteristics. We analysed the results using bivariate and multivariate
      analyses. RESULTS: The response rate was 64% (n = 197). A small majority were
      satisfied with the new EHR (64%, n = 120). Providers who reported satisfaction
      with overall quality of work life, their workload and the transition were more
      likely to be satisfied with the new EHR (P < 0.01). Providers who reported using
      the Internet at least daily were also more likely to be satisfied with the new
      EHR (P < 0.05). In a multivariate model, satisfaction with the transition was a
      strong predictor of satisfaction with the new EHR (P < 0.01). Barriers to
      satisfaction include dissatisfaction with: maintaining problem and medication
      lists, tracking health maintenance information, referring to clinical practice
      guidelines and ordering laboratory and radiology tests (P < 0.01). CONCLUSION:
      This study provides groundwork for understanding the facilitators and barriers to
      provider satisfaction after the transition between EHRs and provides insight into
      areas requiring attention by entities undergoing similar transitions.

PMID- 21883715
TI  - Marginal structural models: much ado about (almost) nothing.
AB  - Marginal structural models were developed to account for a so-called time
      dependent confounder and to estimate the presumed effect of 'treatment regime'
      (treatment over time). We present a set of causal axioms, according to which the
      problem of time-dependent confounding does not exist, and 'treatment regime'
      affects nothing. Per our axiomatization, marginal structural models do not
      introduce a new idea of deconfounding, but simply estimate a weighted average of
      effects. Whenever a weighted average and the weighting scheme can both be
      rationalized, the models are acceptable. Whenever a weighted average does not
      estimate an effect (e.g. important effect modification is ignored), or the
      weights are senseless - the models should not be fit.

PMID- 21883716
TI  - Comparison of tools for the assessment of inappropriate prescribing in
      hospitalized older people.
AB  - RATIONAL, AIMS AND OBJECTIVE: The aim of the present study was to compare the
      ease of use and the capability of four approaches [Medication Appropriateness
      Index (MAI), the Beers' criteria 2003, the Improved Prescribing in the Elderly
      Tool (IPET) and Health Plan Employer Data and Information Set (HEDIS)] in
      assessing changes in medication appropriateness in elderly patients over a period
      of hospitalization. METHODS: A retrospective observational study in two hospitals
      in Northern Ireland using the four measures was undertaken, involving a cohort of
      192 patients (aged > 65 years). Medication appropriateness assessments were made
      at three stages during the patients' hospital 'journey', that is, at admission,
      during their inpatient stay and at discharge. The identifying rates of
      inappropriate prescribing in elderly patients in hospital used validated
      screening tools: MAI, the Beers' criteria 2003, the IPET and HEDIS. RESULTS: The
      MAI was the most comprehensive approach but was also the most time consuming to
      apply. Data derived using the MAI indicated clearly that there was improved
      medication appropriateness over the three hospital stay stages (P < 0.001).
      Although this trend was also significant for the Beers' criteria 2003 (P < 0.05)
      and the IPET (P < 0.05) approaches, the HEDIS was unable to differentiate changes
      in appropriateness over time. There was a good correlation between data derived
      using the MAI and the Beers' criteria 2003 and the IPET approaches; this
      correlation was not evident for the HEDIS. CONCLUSIONS: The MAI is the most
      convincing tool in evaluating medication appropriateness, but is very time
      consuming to apply. Beers' criteria 2003 and the IPET perform to an acceptable
      standard within the clinical setting and are more practical in their application.
      The HEDIS, although simplest to apply, does not have the sensitivity to measure
      change in appropriateness over time.

PMID- 21883717
TI  - Important variations in the content of care pathway documents for total knee
      arthroplasty may lead to quality and patient safety problems.
AB  - AIM: Reducing variations by standardizing the key interventions in clinical
      processes is an effective tool to minimize the probability of medical errors.
      Thus, we determined whether variations exist in the key interventions included in
      care pathway documents (CPDs) of different organizations and in the timing of
      these interventions during the care process. METHODS: We invited members of the
      Belgian Dutch Clinical Pathway Network to send their CPDs for external review. We
      analysed 19 CPDs for total knee arthroplasty. International guidelines were
      consulted for definition of key interventions. Documentation of these
      interventions in the pathway documents was checked. RESULTS: From the 19 CPDs
      analysed, we retrieved 18 key interventions. Nine of these key interventions
      appeared in at least 80% of the care pathways. Only two key interventions
      appeared in all pathway documents. Nine out of 12 interventions that appeared in
      at least 80% of the pathway documents showed a variation of 1 day in the timing
      of care from the median timing. CONCLUSION: We conclude that important variation
      exists in the included interventions and in their timing. The results of this
      study suggest that, before use in daily patient care, CPDs should be reviewed by
      peers and checked to ensure that all evidence-based key interventions are
      included and properly planned. Only in this way can pathways documents be used
      interprofessionally during the entire perioperative period in the search for
      optimal quality and patient safety.

PMID- 21883718
TI  - A tailored educational intervention improves doctor's performance in managing
      depression: a randomized controlled trial.
AB  - RATIONAL AND OBJECTIVES: To assess the effects of a tailored and activating
      educational intervention, based on a three-stage modified Prochaska model of
      readiness-to-change, on the performance of general physicians in primary care
      (GPs) regarding management of depressive disorders. METHODS: Parallel group,
      randomized control trial. Primary hypothesis was that performance would improve
      by 20 percentage units in the intervention arm. The setting was primary care in
      southern Tehran. The participants were 192 GPs stratified on stage of readiness
      to-change, sex, age and work experience. The intervention was a 2-day interactive
      workshop for a small group of GPs' at a higher stage of readiness-to-change
      ('intention') and a 2-day interactive large group meeting for those with lower
      propensity to change ('attitude') at the pre-assessment. GPs in the control arm
      participated in a standard educational programme on the same topic. The main
      outcome measures were validated tools to assess GPs' performance by unannounced
      standardized patients, regarding diagnosis and treatment of depressive disorders.
      The assessments were made 2 months before and 2 months after the intervention.
      RESULTS: GPs in the intervention arm significantly improved their overall mean
      scores for performance regarding both diagnosis, with an intervention effect of
      14 percentage units (P = 0.007), and treatment and referral, with an intervention
      effect of 20 percentage units (P < 0.0001). The largest improvement after the
      intervention appeared in the small group: 30 percentage units for diagnosis (P =
      0.027) and 29 percentage units for treatment and referral (P < 0.0001).
      CONCLUSIONS: Activating learning methods, tailored according to the participants'
      readiness to change, improved clinical performance of GPs in continuing medical
      education and can be recommended for continuing professional development.

PMID- 21883719
TI  - A naive Bayes classifier for planning transfusion requirements in heart surgery.
AB  - RATIONALE, AIMS AND OBJECTIVES: Transfusion of allogeneic blood products is a key
      issue in cardiac surgery. Although blood conservation and standard transfusion
      guidelines have been published by different medical groups, actual transfusion
      practices after cardiac surgery vary widely among institutions. Models can be a
      useful support for decision making and may reduce the total cost of care. The
      objective of this study was to propose and evaluate a procedure to develop a
      simple locally customized decision-support system. METHODS: We analysed 3182
      consecutive patients undergoing cardiac surgery at the University Hospital of
      Siena, Italy. Univariate statistical tests were performed to identify a set of
      preoperative and intraoperative variables as likely independent features for
      planning transfusion quantities. These features were utilized to design a naive
      Bayes classifier. Model performance was evaluated using the leave-one-out cross
      validation approach. All computations were done using spss and matlab code.
      RESULTS: The overall correct classification percentage was not particularly high
      if several classes of patients were to be identified. Model performance improved
      appreciably when the patient sample was divided into two classes (transfused and
      non-transfused patients). In this case the naive Bayes model correctly classified
      about three quarters of patients with 71.2% sensitivity and 78.4% specificity,
      thus providing useful information for recognizing patients with transfusion
      requirements in the specific scenario considered. CONCLUSIONS: Although the
      classifier is customized to a particular setting and cannot be generalized to
      other scenarios, the simplicity of its development and the results obtained make
      it a promising approach for designing a simple model for different heart surgery
      centres needing a customized decision-support system for planning transfusion
      requirements in intensive care unit.

PMID- 21883720
TI  - Evaluating self-efficacy for managing chronic disease: psychometric properties of
      the six-item Self-Efficacy Scale in Germany.
AB  - OBJECTIVE: Self-efficacy - the confidence to carry out certain behaviour in order
      to achieve a specific goal - has increasingly been recognized as an essential
      prerequisite of effective self-management of chronic diseases. Therefore, valid
      and reliable measures are needed to evaluate self-efficacy in both research and
      clinical practice. This study explored the psychometric properties of the German
      version of the Self-Efficacy for Managing Chronic Disease 6-Item Scale (SES6G).
      METHODS: We performed standardized translation and cultural adaptation of the
      SES6G into German. The SES6G was externally validated with the German General
      Self-Efficacy Scale (SWE). Cronbach's alpha, descriptive statistics and principal
      component analysis were used to assess psychometric properties of the SES6G. We
      assessed the effect of the number of co-occurring chronic diseases on SES6G
      scores using linear regression modelling by controlling for age, gender and
      education level. RESULTS: We analysed data of 244 primary care patients in
      Germany. The SES6G showed good convergent construct validity to the SWE (spearman
      rank correlation 0.578, P < 0.001) and high internal consistency (Cronbach's
      alpha 0.930). Principal component analysis underlined the one-dimensional
      structure of the instrument. Adjusted for age and gender, increasing numbers of
      co-occurring chronic diseases were associated with lower SES6G scores
      (standardized beta-value -0.27, P < 0.001). Education level showed no significant
      effect. CONCLUSIONS: The SES6G is a reliable and valid instrument to assess
      patients' self-efficacy for managing chronic diseases. It may enhance further
      research in German-speaking countries and appears to be a valuable measure for
      clinical practice.

PMID- 21883721
TI  - How doctors practice evidence-based medicine.
AB  - RATIONALE AND AIMS: Evidence-based medicine (EBM) has gained worldwide attention.
      Many studies have used questionnaires to discuss factors obstructing the practice
      of EBM. However, no large-scale data analysis has focused on who has practised
      EBM and when they practised it. This retrospective study aims to fill the
      research gap by applying nationally representative data to analyse EBM practice
      after the provision of new evidence regarding the prescription of rosiglitazone
      which has been shown to increase the risk of myocardial infarction. METHODS: We
      used the National Health Insurance Database in Taiwan to analyse the variations
      in rosiglitazone prescription among physicians. The study period was from the
      second quarter of 2007 to the fourth quarter of 2008. A total of 2536 physicians
      who prescribed rosiglitazone at least once were included in this study. We
      applied multivariate logistic analyses to predict the probability of physicians
      ceasing to prescribe rosiglitazone. RESULTS: We observed a significant
      improvement in EBM practice among specialists and experienced physicians.
      Endocrinologists were four times more likely to change rosiglitazone prescription
      habits than other specialists (odds ratio 4.129, 95% confidence interval 2.484
      6.863). Doctors with more than 10 years of specialist experience performed better
      in EBM practice. Moreover, a prominent time lag with more than 6 months between
      EBM emergence and EBM practice was noticed. CONCLUSIONS: Our study suggested that
      EBM was still not well practised, using rosiglitazone prescription as a study
      case. Further education and encouragement to strengthen physicians' EBM practice
      remain urgently needed within the medical community.

PMID- 21883722
TI  - Comparison of two POLQ mutants reveals that a polymerase-inactive POLQ retains
      significant function in tolerance to etoposide and gamma-irradiation in mouse B
      cells.
AB  - DNA polymerase theta (POLQ) is a family A polymerase that contains an intrinsic
      helicase domain. POLQ has been implicated in tolerance to DNA damage but whether
      this depends solely on its polymerase domain remains unknown. In this study, we
      generated POLQ-null CH12F3 B cells by gene targeting and compared their
      sensitivity to DNA-damaging agents with previously established POLQ-inactive
      CH12F3 cells in which only the polymerase core domain was deleted. Compared with
      WT cells, POLQ-null and POLQ-inactive cells exhibited similarly increased
      sensitivity to mitomycin C, cisplatin, and ultraviolet radiation, suggesting that
      tolerance to these DNA-damaging agents depends largely on POLQ polymerase
      activity. Intriguingly, POLQ-null cells exhibited higher sensitivity than did
      POLQ-inactive cells to etoposide and gamma-irradiation, both of which induce
      double-strand breaks (DSBs). This observation indicates that the polymerase
      deleted POLQ, expressed in POLQ-inactive cells, retains significant function in
      tolerance to these agents. Class switch recombination of immunoglobulin genes,
      which involves repair of activation-induced cytidine deaminase (AID)-triggered
      DSBs, however, was unaffected in both POLQ-null and POLQ-inactive cells. These
      results suggest that the polymerase and other functional domains of POLQ both
      play important roles in tolerance to etoposide and gamma-irradiation but are
      dispensable for AID-mediated class switch recombination.

PMID- 21883723
TI  - Review: indications for ultrasound use in low- and middle-income countries.
AB  - OBJECTIVE: To determine the indications for using ultrasound, in low- and middle
      income countries (LMICs) and to assess whether its use alters clinical
      management. METHODS: Literature review. We conducted a Pubmed search on the
      clinical use of ultrasound in LMIC for articles published between January 2000
      and December 2010, recording country of origin, speciality and whether ultrasound
      use led to a change in management. RESULTS: Fifty-eight articles were identified
      from 32 countries and represented nine specialties. Ultrasound was most commonly
      used for assisting with the diagnosis of obstetrical conditions, followed by
      intra-abdominal conditions such as liver abscesses and intussusceptions. Clinical
      management was altered in >30% of cases. CONCLUSION: Ultrasound is a highly
      valuable diagnostic tool in LMICs and its use should be considered essential for
      all district medical facilities. The use could be applied more widely, eg., for
      tropical and non-communicable diseases. Additional research is needed to further
      characterize the impact of task shifting on ultrasound use in LMICs.

PMID- 21883724
TI  - Total lymphocyte count is a good marker for HIV-related mortality and can be used
      as a tool for starting HIV treatment in a resource-limited setting.
AB  - OBJECTIVES: Total lymphocyte counts (TLC) may be used as an alternative for CD4
      cell counts to monitor HIV infection in resource-limited settings, where CD4 cell
      counts are too expensive or not available. METHODS: We used prospectively
      collected patient data from an urban HIV clinic in Indonesia. Predictors of
      mortality were identified via Cox regression, and the relation between TLC and
      CD4 cell counts was calculated by linear regression. Receiver operating
      characteristics (ROC) curves were used to choose the cut-off values of TLC
      corresponding with CD4 cell counts <200 and <=350 cells/MUl. Based on these
      analyses, we designed TLC-based treatment algorithms. RESULTS: Of 889
      antiretroviral treatment (ART)-naive subjects included, 66% had CD4 cell counts
      <200 and 81% had 350 <= cells/MUl at baseline. TLC and CD4 cell count were
      equally strong predictors of mortality in our population, where ART was started
      based on CD4 cell count criteria. The correlation coefficient (R) between TLC and
      ?CD4 was 0.70. Optimal cut-off values for TLC to identify patients with CD4 cell
      counts <200 and <=350 cells/MUl were 1500 and 1700 cells/MUl, respectively.
      Treatment algorithms based on a combination of TLC, gender, oral thrush, anaemia
      and body mass index performed better in terms of predictive value than WHO
      staging or TLC alone. In our cohort, such an algorithm would on average have
      saved $14.05 per patient. CONCLUSION: Total lymphocyte counts is a good marker
      for HIV-associated mortality. Simple algorithms including TLC can prioritize
      patients for HIV treatment in a resource-limited setting, until affordable CD4
      cell counts will be universally available.

PMID- 21883726
TI  - Benefit of viral load testing for confirmation of immunological failure in HIV
      patients treated in rural Malawi.
AB  - OBJECTIVE: Viral load testing is used in the HIV programme of Chiradzulu, Malawi,
      to confirm the diagnosis of immunological failure to prevent unnecessary
      switching to second-line therapy. Our objective was to quantify the benefit of
      this strategy for management of treatment failure in a large decentralized HIV
      programme in Africa. METHODS: Retrospective analysis of monitoring data from
      adults treated with first-line antiretroviral regimens for >1 year and meeting
      the WHO immunological failure criteria in an HIV programme in rural Malawi. The
      positive predictive value of using immunological failure criteria to diagnose
      virological failure (viral load >5000 copies/ml) was estimated. RESULTS: Of the
      227 patients with immunological failure (185 confirmed with a repeat CD4
      measurement), 155 (68.2%) had confirmatory viral load testing. Forty-four (28.4%)
      had viral load >5000 copies/ml and 57 (36.8%) >1000 copies/ml. Positive
      predictive value was 28.4% (95% CI 21.4-36.2%). Repeat CD4 count testing showed
      that 41% of patients initially diagnosed with immunological failure did no longer
      meet failure criteria. CONCLUSIONS: Our results support the need for confirming
      all cases of immunological failure with viral load testing before switching to
      second-line ART to optimize the use of resources in developing countries.

PMID- 21883725
TI  - Failure to test children of HIV-infected mothers in South Africa: implications
      for HIV testing strategies for preschool children.
AB  - OBJECTIVES: To assess the uptake of HIV testing among preschool children with HIV
      positive mothers in a peri-urban population-based study in KwaZulu-Natal, South
      Africa, an area of high HIV prevalence. METHODS: All children 4-6 years old and
      their primary caregivers from the area were invited to participate. All
      participants were asked about prior HIV testing and were offered counselling and
      voluntary HIV testing irrespective of previous testing. Twenty-seven HIV-infected
      mothers were interviewed to identify barriers to testing their children. RESULTS:
      One thousand five hundred and eighty-three children (88% of eligible children)
      and their caregivers participated. Of the biological mothers, 86% were previously
      tested for HIV (27% tested positive). Among the surviving 244 children born to an
      infected mother, only 41% had been tested for HIV (23% tested positive).
      Subsequently, 90% of previously untested children of infected mothers underwent
      HIV testing (9.3% were positive). Overall seroprevalence among study children was
      4.9%. All infected mothers interviewed endorsed the belief that children of HIV
      infected women should be tested for HIV. Women who missed opportunities for
      antenatal HIV testing reported no systematic testing of their children at later
      ages. CONCLUSIONS: In this community with high HIV prevalence, HIV testing of
      children is infrequent despite high testing coverage among caregivers. The low
      proportion of children tested for HIV, particularly those of infected mothers, is
      of great concern as they are at high risk for morbidity and mortality associated
      with untreated childhood HIV infection. HIV testing programs should strengthen
      protocols to include children, especially for those who missed PMTCT
      opportunities in infancy.

PMID- 21883727
TI  - Ownership and use of insecticide-treated nets in Oromia and Amhara regional
      states of Ethiopia two years after a nationwide campaign.
AB  - OBJECTIVE: To evaluate the ownership and use of insecticide-treated nets (ITNs)
      by the local community 2 years after a free distribution campaign in Ethiopia.
      METHODS: This is a population-based survey using a two-stage cluster sample
      design in 115 randomly selected clusters in Oromia and Amhara regional states of
      Ethiopia, performed in June 2009. Data on the possession and use of ITNs were
      collected using structured and pre-tested questionnaires through house-to-house
      visits. Bivariate and multivariate logistic regression analyses were performed to
      examine the effect of participant's malaria knowledge, location and ITN
      characteristics on the use of ITNs. RESULTS: A total of 2874 households
      participated in the study, and 90.6% of the study population was knowledgeable
      about ITNs. About 49.1% of households reported at least one ITN; 28.4% owned two
      or more. ITN coverage was significantly lower in Oromia (34.9%) than in Amhara
      (76.8%, P<0.001). The average number of ITNs per ITN-owning household was 1.8. In
      all surveyed households, only 21.8% of all family members, 29.4% of all children
      under the age of 5 years and 23.2% of all pregnant women had slept under an ITN
      the night preceding the survey. Among ITN-owning households, 63.0% of all
      children under the age of 5 years and 52.1% of pregnant women had slept under an
      ITN the night before the survey. Using multivariate analysis, factors
      significantly associated with ITN use were number of ITNs in the household,
      number of ITNs hung over the bed in the household, women's knowledge of ITNs and
      women's lack of problem in using ITNs, whereas region, area of residence and ITN
      status were not. CONCLUSIONS: Household ITN ownership and use remain below the
      current Roll Back Malaria targets of universal coverage. A replacement strategy
      is urgently needed to scale-up coverage and use of ITNs.

PMID- 21883728
TI  - Francisella halioticida sp. nov., a pathogen of farmed giant abalone (Haliotis
      gigantea) in Japan.
AB  - AIMS: In 2005, a Francisella sp. was isolated from diseased cultured giant
      abalone (Haliotis gigantea) in Japan. The aim of this study was to clarify the
      taxonomic status of this Francisella sp. Shimane-1 isolate in relation to the
      four described Francisella species. METHODS AND RESULTS: The 16S rRNA gene and
      several housekeeping genes of the Shimane-1 were compared to isolates of the four
      recognized species within the Francisella genus. DNA-DNA hybridization (DDH) and
      biochemical profile comparison were performed with the two phylogenetically
      closely related species, Francisella philomiragia and Francisella noatunensis.
      Results show that the Shimane-1 is genetically different from all described
      Francisella species and differs phenotypically from F. philomiragia and F.
      noatunensis. The average DDH similarity of Francisella sp. Shimane-1 to F.
      noatunensis ssp. noatunensis (NCIMB14265(T)) and to F. philomiragia (DSM7535(T))
      was 49.2 and 61%, respectably, clearly supporting the establishment of Shimane-1
      as a new species within the Francisella genus. CONCLUSIONS: The phenotypic and
      genetic results presented in this study suggest the establishment of Shimane-1 as
      a novel species, for which the name Francisella halioticida sp. nov.
      (=LMG26062(T), =DSM23729(T)) is proposed. SIGNIFICANCE AND IMPACT OF THE STUDY:
      This study clarifies the taxonomic position and characteristics of a novel
      mollusc pathogenic Francisella species.

PMID- 21883729
TI  - Modelling the effect of water activity and temperature on growth rate and
      aflatoxin production by two isolates of Aspergillus flavus on paddy.
AB  - AIMS: This study was conducted to characterize the growth of and aflatoxin
      production by Aspergillus flavus on paddy and to develop kinetic models
      describing the growth rate as a function of water activity (a(w)) and
      temperature. METHODS AND RESULTS: The growth of A. flavus on paddy and aflatoxin
      production were studied following a full factorial design with seven a(w) levels
      within the range of 0.82-0.99 and seven temperatures between 10 and 43 degrees C.
      The growth of the fungi, expressed as colony diameter (mm), was measured daily,
      and the aflatoxins were analysed using HPLC with a fluorescence detector. The
      maximum colony growth rates of both isolates were estimated by fitting the
      primary model of Baranyi to growth data. Three potentially suitable secondary
      models, Rosso, polynomial and Davey, were assessed for their ability to describe
      the radial growth rate as a function of temperature and a(w). Both strains failed
      to grow at the marginal temperatures (10 and 43 degrees C), regardless of the
      a(w) studied, and at the a(w) level of 0.82, regardless of temperature. Despite
      that the predictions of all studied models showed good agreement with the
      observed growth rates, Davey model proved to be the best predictor of the
      experimental data. The cardinal parameters as estimated by Rosso model were
      comparable to those reported in previous studies. Toxins were detected in the
      range of 0.86-0.99 a(w) with optimal a(w) of 0.98 and optimal temperature in the
      range of 25-30 degrees C. CONCLUSIONS: The influences of a(w) and temperature on
      the growth of A. flavus and aflatoxin production were successfully characterized,
      and the models developed were found to be capable of providing good, related
      estimates of the growth rates. SIGNIFICANCE AND IMPACT OF THE STUDY: The results
      of this study could be effectively implemented in minimizing the risk of
      aflatoxin contamination of the paddy at postharvest.

PMID- 21883730
TI  - Analysis of the germination of individual Clostridium perfringens spores and its
      heterogeneity.
AB  - AIMS: To analyse the germination and its heterogeneity of individual spores of
      Clostridium perfringens. METHODS AND RESULTS: Germination of individual wild-type
      Cl. perfringens spores was followed by monitoring Ca-dipicolinic acid (CaDPA)
      release and by differential interference contrast (DIC) microscopy. Following the
      addition of KCl that acts via germinant receptors (GRs), there was a long
      variable lag period (T(lag)) with slow release of c. 25% of CaDPA, then rapid
      release of remaining CaDPA in c. 2 min (DeltaT(release)) and a parallel decrease
      in DIC image intensity, and a final decrease of c. 25% in DIC image intensity
      during spore cortex hydrolysis. Spores lacking the essential cortex-lytic enzyme
      (CLE) (sleC spores) exhibited the same features during GR-dependent germination,
      but with longer average T(lag) values, and no decrease in DIC image intensity
      because of cortex hydrolysis after full CaDPA release. The T(lag) of wild-type
      spores in KCl germination was increased significantly by lower germinant
      concentrations and suboptimal heat activation. Wild-type and sleC spores had
      identical average T(lag) and DeltaT(release) values in dodecylamine germination
      that does not utilize GRs. CONCLUSIONS: Most of these results were essentially
      identical to those reported for the germination of individual spores of Bacillus
      species. However, individual sleC Cl. perfringens spores germinated inefficiently
      with either KCl or exogenous CaDPA, in contrast to CLE-deficient Bacillus spores,
      indicating that germination of these species' spores is not completely identical.
      SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides information on the
      kinetic germination and its heterogeneity of individual spores of Cl.
      perfringens.

PMID- 21883731
TI  - Biosynthesis of cyclodextrin glucosyltransferase by the free and immobilized
      cells of Bacillus cereus NRC7 in batch and continuous cultures.
AB  - AIMS: The objective of this study was to enhance the production of cyclodextrin
      glucanotransferase (CGTase) produced by a local isolate Bacillus cereus NRC7.
      METHODS AND RESULTS: In batch culture, maximal CGTase activity (69.0 U ml(-1))
      was reached after 24-h incubation period. In continuous production of CGTase by
      the free cells of B. cereus NRC7, maximal reactor productivity (11.76 KU l(-1) h(
      1)), with enzyme concentration of 49.0 U ml(-1) and specific productivity of
      904.6 U per g wet cells per h, was attained at dilution rate of 0.24 h(-1), over
      a period of 640 h. Bacillus cereus NRC7 cells were immobilized on chitosan. The
      immobilization conditions with respect to matrix concentration and maximal cell
      loading were optimized for maximal CGTase production. In repeated batch
      operation, the activity of the immobilized cells was stable during ten cycles and
      the activity remained between 51 and 55 U ml(-1). In packed-bed reactor, the
      immobilized cells showed maximal productivity (27.18 KU l(-1) h(-1)) with enzyme
      concentration of 54.63 U ml(-1) and specific productivity of 151.89 U per g wet
      cells per h at dilution rate of 0.5 h(-1). The half-life of the immobilized cells
      was higher than 20 days. CONCLUSIONS: Continuous fermentation by the immobilized
      cells in packed-bed reactor is an appropriate potential technique for B. cereus
      NRC7 CGTase production that gave maximum productivity (27.18 KU l(-1) h(-1)),
      which was 9.47-, 2.31-, 12.24- and 12.94-fold higher than the free cells in
      batch, free cells in continuous, immobilized cells in batch and repeated batch
      cultures, respectively. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first
      study that evaluates CGTase productivity, in different fermentation modes, in
      terms of specific productivity (U per gram cells per h). In continuous
      fermentation by immobilized cells, maximal levels of CGTase productivity are
      higher than the previously reported values.

PMID- 21883732
TI  - Use of ceramic-based cell immobilization to produce 1,3-propanediol from
      biodiesel-derived waste glycerol with Klebsiella pneumoniae.
AB  - AIMS: The feasibility of the continuous production of a valuable bioplastic raw
      material, namely 1,3-propanediol (1,3-PDO) from biodiesel by-product glycerol,
      using immobilized cells was investigated. In addition, the effect of hydraulic
      retention time (HRT) was also analysed. METHODS AND RESULTS: Ceramic balls and
      ceramic rings were used for the immobilization of a locally isolated strain;
      Klebsiella pneumoniae (GenBank no. 27F HM063413). HRT of 1 h is the best one in
      terms of volumetric production rate (g 1,3-PDO l(-1) h(-1)). The results
      indicated that ceramic-based cell immobilization achieved a 2-fold higher
      production rate (10 g 1,3-PDO l(-1) h(-1)) in comparison with suspended cell
      system (4.9 g 1,3-PDO l(-1) h(-1)). CONCLUSIONS: Continuous cultures with
      immobilized cells revealed that 1,3-PDO production was more effective and more
      stable than suspended culture systems. Furthermore, cell immobilization had also
      obvious benefits especially for resistance of the production for extreme
      conditions (high organic loading rates, cell washouts). The results were
      important for understanding the significance of continuous immobilization process
      among other well-known 1,3-PDO fermentation processes. SIGNIFICANCE AND IMPACT OF
      THE STUDY: This work is a promising process for further studies, as the
      immobilized micro-organism was able to reach high volumetric production rates at
      short HRT, it has an important role in tolerating and converting glycerol during
      fermentation. Therefore, HRT is a very significant operational parameter (P value
      <0.05) directly affecting the bioreactor performance and production rate.

PMID- 21883733
TI  - An in vitro model for the growth and analysis of chronic wound MRSA biofilms.
AB  - AIMS: To develop an in vitro model (Colony/drip-flow reactor - C/DFR) for the
      growth and analysis of methicillin-resistant Staphylococcus aureus (MRSA)
      biofilms. METHODS AND RESULTS: Using the C/DFR model, biofilms were grown on the
      top of polycarbonate filter membranes inoculated with a clinical isolate of MRSA,
      placed on absorbent pads in the DFR and harvested after 72 h. The biofilms varied
      from 256 to 308 MUm in thickness with a repeatability standard deviation of 0.22.
      Testing of antimicrobial agents was also performed where C/DFR biofilms were
      grown in parallel with conventional colony biofilms. A saline solution (control),
      1% silver sulfadiazine solution, and 0.25% Dakin's solution were used to treat
      the biofilms for 15 min. Microscopic evaluation of biofilm morphology and
      thickness was conducted. The Dakins solution in both models produced
      statistically significantly higher log reductions than silver sulfadiazine
      treatment. CONCLUSIONS: The C/DFR biofilms were thick and repeatable and
      exhibited higher resistance to Dakins solution than the treated colony biofilms.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The C/DFR can be used as a tool for
      examining complex biofilm physiology as well as for performing comparative
      experiments that test wound care products and novel antimicrobials.

PMID- 21883734
TI  - Bovine recto-anal junction squamous epithelial (RSE) cell adhesion assay for
      studying Escherichia coli O157 adherence.
AB  - AIM: To develop a new adherence assay, using cattle recto-anal junction squamous
      epithelial (RSE) cells, for evaluating bacterial adherence to cells of bovine
      origin. METHODS AND RESULTS: Proof of concept was demonstrated using the human
      gastrointestinal pathogen Escherichia coli O157:H7, for which cattle are
      reservoirs. Adherence assays were conducted using both RSE and HEp-2 cells, in
      the presence and absence of D+Mannose. E. coli O157 specifically adhered in a
      type I fimbriae-independent manner to RSE cells in significantly higher numbers
      and also bound significantly higher numbers of RSE cells than diverse laboratory
      strains of nonpathogenic E. coli. CONCLUSION: The RSE cell adhesion assay output
      highly reproducible and interpretable results that compared very well with those
      obtained using the more extensively used HEp-2 cell adherence assay. SIGNIFICANCE
      AND IMPACT OF THE STUDY: The RSE cell adhesion assay provides a convenient means
      of directly defining and evaluating pathogen factors operating at the bovine
      recto-anal junction. The RSE cell adhesion assay further has the potential for
      extrapolation to diverse bacteria, including food-borne pathogens that colonize
      cattle via adherence to this particular anatomical site.

PMID- 21883735
TI  - Enhancement of phenol degradation by soil bioaugmentation with Pseudomonas sp.
      JS150.
AB  - AIMS: To test whether bioaugmentation with genetically modified Pseudomonas sp.
      JS150 strain could be used to enhance phenol degradation in contaminated soils.
      METHODS AND RESULTS: The efficiency of phenol removal, content of humic carbon,
      survival of inoculant, number of total culturable autochthonous bacteria and
      changes in fatty acid methyl esters (FAME) profiling obtained directly from soils
      were examined. Bioaugmentation significantly accelerated phenol biodegradation
      rate in tested soils. Phenol applied at the highest concentration (5.0 mg g(-1)
      soil) was completely degraded in clay soil (FC) within 65 days, whereas in sand
      soil (FS) within 72 days. In comparison, phenol biodegradation proceeded for 68
      and 96 days in nonbioaugmented FC and FS soils, respectively. The content of
      humic carbon remained at the same level at the beginning and the end of
      incubation time in all soil treatments. The number of introduced bacteria (2.50 *
      10(9) g(-1) soil) markedly decreased during the first 4 or 8 days depending on
      contamination level and type of soil; however, inoculant survived over the
      experimental period of time. Analysis of FAME patterns indicated that changes in
      the percentages of cyclopropane fatty acids 17:0 cy and 19:0 cyomega10c and
      branched fatty acids might be useful markers for monitoring the progress of
      phenol removal from soil. CONCLUSIONS: It was confirmed that soil bioaugmentation
      with Pseudomonas sp. JS150 significantly enhanced soil activity towards phenol
      degradation. Cyclopropane and branched fatty acids were sensitive probes for
      degree of phenol utilization. SIGNIFICANCE AND IMPACT OF THE STUDY: In future,
      genetically modified Pseudomonas sp. JS150 strain could be of use in the
      bioaugmentation of phenol-contaminated areas.

PMID- 21883736
TI  - Four-year follow-up of two chronic hepatitis B recipients of hepatitis B surface
      antigen-positive cadaveric liver grafts from asymptomatic carriers.
AB  - AIM:   Only seven cases of liver transplantation (OLT) with positive serum
      hepatitis B surface antigen (HBsAg) grafts have been reported in the world till
      now. Here we report the 4-year follow-up results and clinical pathologic
      characteristics of two recipients of chronic hepatitis B transplanted with HBsAg
      positive cadaveric liver grafts from asymptomatic carriers. METHODS:   Lamivudine
      combined with hepatitis B immune globulin were used for the control of hepatitis
      B virus (HBV) infection in both of the recipients post-OLT. The liver functions,
      virus status and pathologic characteristics of two recipients were followed up
      according to the rounte protocol of Liver Transplantation Center of West China
      Hospital. RESULTS:   The serum HBV deoxyribonucleic acid (DNA) turned negative
      within 30 days post-OLT, but HBsAg remained positive for both of the recipients
      during follow up. HBV breakthrough occurred in one recipient at the month 12 post
      OLT, with detectable serum HBV-DNA (740 copies/mL) and tyrosine-methionine
      aspartate-aspartate motif mutation (rtM204I and rtM204V). After the replacement
      of lamivudine by adefovir dipivoxil 10 mg daily for 2 months, serum HBV-DNA of
      this recipient became undetectable again and maintained undetectable during
      follow up. Both of the recipients have survived for more than 4 years post-OLT,
      with stable liver function and mild hepatitis. CONCLUSION:   Due to extreme
      scarcity of liver graft, we think that HBsAg-positive liver graft without active
      HBV-DNA replication and severe pathological manifestation from asymptomatic
      carriers may deserve consideration when no other graft is available in a bearable
      waiting time.

PMID- 21883737
TI  - Development rate of chronic kidney disease in hepatitis C virus patients with
      advanced fibrosis after interferon therapy.
AB  - AIM:   The aim of this retrospective cohort study is to assess the development
      incidence and predictive factors for chronic kidney disease (CKD) after the
      termination of interferon therapy in hepatitis C virus (HCV) positive Japanese
      patients with liver cirrhosis. METHODS:   A total of 650 HCV positive, liver
      cirrhotic patients who were treated with interferon and showed an estimated
      glomerular filtration rate (eGFR) of >=60 mL/min per 1.73 m(2)  after the
      termination of interferon therapy were enrolled. CKD was defined as an eGFR of
      <60 mL/min per 1.73 m(2) . End-stage-CKD was defined as an eGFR of <15
      mL/min/1.73 m(2) . The primary goal is the new development of CKD and end-stage
      CKD. RESULTS:   Eighty-five patients developed CKD, and six patients progressed
      to end-stage-CKD. The development rate of CKD was 5.2% at the 5th year, 14.5% at
      the 10th year and 30.6% at the 15th year. Multivariate Cox proportional hazards
      analysis showed that CKD occurred when patients had age increments of 10 years
      (hazard ratio: 2.32; 95% confidence interval [CI] 1.61-3.35; P < 0.001), eGFR
      decrements of 10 mL/min per 1.73 m(2)  (hazard ratio: 1.66; 95% CI 1.27-2.16; P <
      0.001), hypertension (hazard ratio: 2.00; 95% CI 1.13-3.53; P = 0.017), diabetes
      (hazard ratio: 1.79; 95% CI 1.02-3.14; P = 0.042), and non-clearance of HCV
      (hazard ratio: 2.67; 95% CI 1.34-5.32; P = 0.005). The development rate of end
      stage-CKD was 0.4% at the 5th year, 1.6% at the 10th year and 2.8% at the 15th
      year. CONCLUSIONS:   The annual incidence for CKD among cirrhotic patients with
      HCV was determined to be about 1.0-1.5%. In addition, the annual incidence for
      end-stage-CKD is one order of magnitude lower than that of CKD.

PMID- 21883738
TI  - Primary biliary cirrhosis - Autoimmune hepatitis overlap syndrome: A rationale
      for corticosteroids use based on a nation-wide retrospective study in Japan.
AB  - AIMS:   Primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH) may
      simultaneously coexist in some patients, designated as PBC-AIH overlap syndrome.
      Previous studies suggest that combination therapy of ursodeoxycholic acid (UDCA)
      and corticosteroids may be effective. In the current study, we aimed to describe
      clinical features of these cases and to propose a rationale for combination
      treatment in PBC-AIH overlap. METHODS:   We enrolled patients with PBC-AIH
      overlap from eight referral centers for liver diseases in Japan, and clinical,
      biochemical and immunological features were examined. Liver histology of all
      patients at diagnosis were analyzed altogether in detail. Eighty-nine and 44
      patients with PBC and AIH alone were included and served as controls. RESULTS:  
      We identified 33 patients with PBC-AIH overlap. The mean follow-up period was 6.1
      years. On liver histology, the HA (hepatitis activity) score was significantly
      higher than the CA (cholangitis activity) score (P < 0.001). At the end of the
      follow-up period, corticosteroids were used in 23 patients (72%), and neither
      liver-related death nor liver transplantation had been noted. The sensitivity and
      specificity of the simplified AIH scoring system for prediction of patients who
      required corticosteroids during clinical course was 92% and 75% in the training
      set (n = 17), and 91% and 80% in the validation set (n = 16) of overlap. Only 3%
      of PBC patients were diagnosed as having indication for corticosteroid use.
      CONCLUSION:   In PBC-AIH overlap, AIH-like features are dominant in liver
      histology. The simplified AIH scoring system could predict patients who needed
      corticosteroids with a higher specificity.

PMID- 21883739
TI  - Liver stiffness measured by transient elastography is a predictor of
      hepatocellular carcinoma development in viral hepatitis.
AB  - AIM:   To investigate the value of liver stiffness in diagnosing hepatocellular
      carcinoma (HCC) among patients with viral hepatitis, and to prospectively
      investigate relationships between liver stiffness and HCC development. METHODS:  
      Liver stiffness was measured by transient elastography for 157 patients with
      viral hepatitis, along with various other parameters potentially associated with
      HCC. HCC was initially present in 41 patients and absent in 116 patients, of whom
      106 patients were followed prospectively for HCC development. Diagnostic
      performances of liver stiffness and other clinical parameters in predicting
      presence of HCC were evaluated using receiver operating characteristic (ROC)
      curves and area under the ROC curve (AUROC). RESULTS:   Liver stiffness was
      significantly higher in patients with HCC (24.9 +/- 19.5 kPa) than in patients
      without HCC (10.9 +/- 8.4 kPa; P < 0.0001). Age (P < 0.0001), platelet cell count
      (P = 0.0001), prothrombin activity (P = 0.0009), alpha fetoprotein (P = 0.0091),
      and des-gamma-carboxy prothrombin (DCP) (P = 0.0099) also differed significantly
      between patients with and without HCC. The largest AUROC was for liver stiffness.
      Differences between liver stiffness and age, platelet cell count, prothrombin
      activity, and DCP were not significant, but the AUROC of liver stiffness was
      superior to that of alpha fetoprotein (P = 0.03850). Using a cut-off liver
      stiffness of 12.5 kPa, development of HCC was identified in 10 of the 106
      patients followed. Multivariate analysis identified liver stiffness >=12.5 kPa,
      age >=60 years, and serum total bilirubin >=1.0 mg/dL as significantly correlated
      with development of HCC. CONCLUSIONS:   Liver stiffness as measured by transient
      elastography is a predictor of HCC development in viral hepatitis.

PMID- 21883740
TI  - Characterization of hepatocellular adenoma based on the phenotypic
      classification: The Kanazawa experience.
AB  - AIM:   Hepatocellular adenoma (HCA) represents a heterogeneous entity, and
      recently four major subgroups were identified based on genotype and phenotype
      classification from Europe. HCA is rare in Asian countries including Japan and
      there has been no study regarding the subgroups of HCA in Japan. METHODS:   We
      took advantage of the reported genotype/phenotype classification to analyze 14
      HCA (seven women) in Japan. RESULTS:   We identified one hepatocyte nuclear
      factor (HNF)1alpha-inactivated HCA (one woman), two beta-catenin-activated HCA
      (one woman), seven inflammatory HCA (IHCA, two women); four additional cases
      (three women) had no known phenotypic marker (unclassified HCA). The use of oral
      contraceptives was found only in two unclassified HCA (29%) cases. Fatty change
      of the background liver was seen in one beta-catenin-activated HCA cases, four
      IHCA (57%) and two unclassified HCA (50%). Hepatic fibrosis was seen in five IHCA
      (71%) and two unclassified HCA (50%) cases. Four IHCA patients (one woman) were
      alcohol drinkers and one had alcoholic steatofibrosis and three had alcoholic
      cirrhosis. Eight HCA (57%) were multiple; one HNF1alpha-inactivated HCA (100%),
      four IHCA (57%) and three unclassified HCA (75%). The tumor was significantly
      larger in beta-catenin-activated HCA than in other subgroups. The association of
      hepatocellular carcinoma was seen only in one case of unclassified HCA.
      CONCLUSION:   This study suggests that IHCA arising in men with alcoholic liver
      disease may be a major subtype of HCA in Japan.

PMID- 21883741
TI  - Highly sensitive AFP-L3% assay is useful for predicting recurrence of
      hepatocellular carcinoma after curative treatment pre- and postoperatively.
AB  - AIM:   The micro-total analysis system (uTAS), a fully automated immunoassay
      system using microchip capillary electrophoresis, is highly sensitive and able to
      quickly assay the AFP-L3%. The clinical usefulness of this system was studied.
      METHODS:   We retrospectively enrolled 250 patients who underwent curative
      treatment for primary hepatocellular carcinoma (HCC) (93 patients underwent
      hepatic resection and 157, radiofrequency ablation [RFA]). RESULTS:   The
      sensitivity for uTAS AFP-L3% was 40.3% at the cutoff value of 5% in a range of
      AFP less than 20 ng/mL where the conventional method was unable to determine AFP
      L3%. The sensitivity for AFP-L3% remained high even at stage I and at tumor size
      less than 2 cm (42.5% and 46.0%, respectively). Recurrence rate of patients with
      AFP-L3% greater than 5% was significantly higher than that of patients with less
      than 5% (P = 0.001). Furthermore, in resected patients, the postoperative AFP-L3%
      remained elevated with value greater than 5% was related to HCC recurrence (P =
      0.001). Multivariate analysis revealed that multiple tumors (P = 0.004),
      preoperative AFP-L3% greater than 5% (P = 0.003), albumin less than 3.5 g/dL (P =
      0.008), and RFA (P = 0.003) were significant prognostic factors of recurrence.
      CONCLUSIONS:   The uTAS was found to be a highly sensitive assay for AFP-L3% in
      patients with curative treatment of HCC. A cutoff value of 5% was useful for
      predicting recurrence after the curative treatment and detecting small tumors and
      early stage HCC. Additionally, postoperative AFP-L3% was found to be a prognostic
      factor of HCC recurrence.

PMID- 21883742
TI  - Easy-to-use phylogenetic analysis system for hepatitis B virus infection.
AB  - AIM:   The molecular phylogenetic analysis has been broadly applied to clinical
      and virological study. However, the appropriate settings and application of
      calculation parameters are difficult for non-specialists of molecular genetics.
      In the present study, the phylogenetic analysis tool was developed for the easy
      determination of genotypes and transmission route. METHODS:   A total of 23
      patients of 10 families infected with hepatitis B virus (HBV) were enrolled and
      expected to undergo intrafamilial transmission. The extracted HBV DNA were
      amplified and sequenced in a region of the S gene. RESULTS:   The software to
      automatically classify query sequence was constructed and installed on the
      Hepatitis Virus Database (HVDB). Reference sequences were retrieved from HVDB,
      which contained major genotypes from A to H. Multiple-alignments using CLUSTAL W
      were performed before the genetic distance matrix was calculated with the six
      parameter method. The phylogenetic tree was output by the neighbor-joining
      method. User interface using WWW-browser was also developed for intuitive
      control. This system was named as the easy-to-use phylogenetic analysis system (E
      PAS). Twenty-three sera of 10 families were analyzed to evaluate E-PAS. The
      queries obtained from nine families were genotype C and were located in one
      cluster per family. However, one patient of a family was classified into the
      cluster different from her family, suggesting that E-PAS detected the sample
      distinct from that of her family on the transmission route. CONCLUSIONS:   The E
      PAS to output phylogenetic tree was developed since requisite material was
      sequence data only. E-PAS could expand to determine HBV genotypes as well as
      transmission routes.

PMID- 21883743
TI  - DNA repair gene XRCC7 polymorphisms (rs#7003908 and rs#10109984) and
      hepatocellular carcinoma related to AFB1 exposure among Guangxi population,
      China.
AB  - AIM:   The X-ray repair cross-complementing group 7 (XRCC7) plays an important
      role in the repair of DNA double-strand breaks by nonhomologous end-joining
      repair (NEJR) pathway. However, the role of XRCC7 polymorphisms (rs#7003908 and
      rs#10109984) possibly influencing NEJR capacity in hepatocellular carcinoma (HCC)
      induced by aflatoxin B1 (AFB1) has not been well elaborated. METHODS:   This
      hospital-based case-control study, including 348 patients with newly diagnosed
      HCC and 597 controls without any evidence of liver diseases, was conducted to
      elucidate the association between these two polymorphisms and the risk of HCC
      related to AFB1 exposure among a Guangxi population from a high AFB1-exposure
      area by means of TaqMAN-polymerase chain reaction technique. RESULTS:   We
      observed that HCC patients featured higher AFB1 exposure than control group (odds
      ratios [OR] = 6.49 and 6.75 for exposure years and exposure levels,
      respectively). Furthermore, these individuals with the genotypes of XRCC7
      rs#7003908 G alleles (namely XRCC7-TG or -GG), compared the homozygote of XRCC7
      rs#7003908 T alleles (XRCC7-TT), faced increasing risk of HCC (OR, 3.45 and 5.04;
      95% confidence intervals [CIs], 2.40-4.94 and 3.28-7.76, respectively). We also
      found some evidence that this polymorphism interacted with AFB1-expousure years
      or levels in the process of HCC carcinogenesis. Additionally, XRCC7 rs#7003908
      polymorphism was correlated with the levels of AFB1-DNA adducts (r = 0.142, P <
      0.001). XRCC7 rs#10109984 polymorphism, however, did not modify the risk of HCC
      related to AFB1 exposure (P > 0.05). CONCLUSION:   These data suggest that XRCC7
      rs#7003908 polymorphism may be one of the genetic modifiers for AFB1-related HCC
      among Guangxi population.

PMID- 21883744
TI  - Renal function in children with heart transplantation after switching to CNI-free
      immunosuppression with everolimus.
AB  - Renal impairment because of CNI contributes to long-term morbidity. Therefore,
      CNI avoiding or sparing treatment strategies are important. In this article, we
      describe the results of a CNI-free treatment protocol with regard to recovery of
      renal function. Twenty-eight patients with heart transplantation were switched
      from CNI regimen to everolimus and mycophenolate, when cGFR was <75 mL/min/1.73
      m(2). In all patients, CNI was stopped, when everolimus trough levels of 5-8 ng/L
      were achieved. Serum creatinine and cGFR were determined before and after 6 and
      12 months. Median serum creatinine decreased from 1.2 mg/dL (range 0.7-3.7)
      before everolimus to 1.0 (range 0.6-1.8) and 1.0 (range 0.5-1.9) mg/dL after 6
      and 12 months. Median cGFR was 47.81 (range 18.3-72.6) mL/min/1.73 m(2) before
      everolimus and 63.1 (range 37.8-108.7) mL/min/1.73 m(2) at six months and 64.8
      (range 37.7-106.6) mL/min/1.73 m(2) after 12 months. All changes from baseline to
      six and 12 months were statistically significant (p < 0.05). Adverse events were
      infections (n = 3) and rejections (n = 3). Therapy was discontinued in four
      patients. Conversion to CNI-free immunosuppression resulted in significant
      improvements of renal function within six months of CNI withdrawal. Side effects
      are common. However, more studies are required to demonstrate the effectiveness
      in children.

PMID- 21883745
TI  - Severe calcification of the aorta (porcelain aorta) associated with sarcoidosis
      in a pediatric heart transplant recipient.
AB  - We report a unique case of severe calcification of the aorta, bilateral coronary
      ostial stenoses and calcification of the mitral valve and left ventricle due to
      sarcoidosis. The patient underwent neonatal orthotopic heart transplantation
      secondary to hypoplastic left heart syndrome and developed hypercalcemia with
      other features of sarcoidosis at 10 yr of age. The mechanism for severe extra
      renal calcification localized to the allograft is poorly understood, but may
      involve discordant local immune modulation and/or calcification-regulation
      between graft and host tissues.

PMID- 21883746
TI  - Is there a role for oral human immunoglobulin in the treatment for norovirus
      enteritis in immunocompromised patients?
AB  - No treatment for NVE is available. Immunocompromised patients with NVE treated
      with OHIG (12 cases) were retrospectively identified and matched 1:1 by age and
      gender with immunocompromised patients with NVE not treated with OHIG (12
      controls). Chi-squared test, t-test, bivariate conditional linear regression
      analyses, and Kaplan-Meier curve were performed. A total of 58.3% patients were
      small bowel transplant (SBT) recipients. Although not statistically significant,
      cases compared with controls were more likely to have had induction therapy (p =
      0.25, OR = 65.3), higher peak tacrolimus levels (p = 0.43, OR = 1.04), SBT (p =
      0.30, OR = 65.3), prior NVE (p = 0.42, OR = 2.0), TPN support (p = 0.42 OR =
      2.0), and decrease in immunosuppression (p = 0.14, OR = 5.0). Treatment with OHIG
      favored resolution of diarrhea (p = 0.078, OR = 65.3) and decreased stool output
      seven days after treatment compared with controls (mean difference 11.95
      mL/kg/day, p = 0.09). OHIG did not impact total time to resolution of diarrhea
      (mean 12.08 vs. 11.91 days; p = 0.63), length of hospital stay (p = 0.31, OR =
      1.05), or cost of hospitalization (p = 0.32, OR = 1.0). We show a potential role
      of OHIG treatment for NVE. Resolution of diarrhea and decreased stool output were
      observed at seven days; no benefit was found for length of hospital stay or
      hospital cost.

PMID- 21883747
TI  - A clinically significant interaction between tacrolimus and multiple proton pump
      inhibitors in a kidney transplant recipient.
AB  - The shared metabolism of PPIs and tacrolimus through the CYP enzyme system has
      been associated with clinically significant drug interactions, especially in
      patients who are classified as CYP 2C19 PMs. However, existing data are
      conflicting, indicating that a single mechanism does not account for all
      interactions. A drug interaction between tacrolimus and omeprazole, esomeprazole,
      but not lansoprazole, occurred in an 18-yr-old female kidney transplant recipient
      classified as a CYP 2C19 extensive (normal) metabolizer. This case suggests that
      further research is needed to establish the definitive mechanism of this
      potentially serious drug-drug interaction. Physicians prescribing PPIs in organ
      transplant recipients with tacrolimus immunosuppression should consider close
      pharmacokinetic monitoring of tacrolimus when starting or switching a PPI.

PMID- 21883748
TI  - Severe hyperinsulinemia, decreased GLUT3 and GLUT4 expression, and increased
      retinol binding protein 4 in a patient with chronic graft-versus-host disease
      post bone marrow transplantation.
AB  - Hyperinsulinemia with or without DM2 is a frequent long-term sequela of BMT,
      especially following cGvHD. In this report, an extensive evaluation of a patient
      with cGvHD is described: glucose and insulin during OGTT, markers of
      inflammation, adiponectin and RBP4, body composition analysis, and the kinetics
      of GLUT3 and GLUT4 in circulating monocytes were evaluated. Hyperinsulinemia,
      associated with partial lipodystrophy, elevated RBP4, low adiponectin levels, and
      decreased expression of GLUT3 and GLUT4 were detected. The defects disclosed in
      this particular patient possibly explain, at least in part, the mechanisms
      underlying insulin resistance in patients undergoing BMT. It is not clear whether
      insulin resistance was caused by the drugs, the process itself, or the residual
      damage to the muscles and/or adipose tissue.

PMID- 21883750
TI  - Impact of donor cardiopulmonary resuscitation on pediatric heart transplant
      outcome.
AB  - Mortality is the highest of any solid organ in pediatric patients awaiting heart
      transplantation. Strategies to increase the donor pool are needed if survival to
      transplant is to improve. There can be reluctance to accept pediatric hearts for
      transplantation if the donor has received cardiopulmonary resuscitation (CPR).
      This study asked if donor CPR impacts the survival of pediatric heart transplant
      recipients. Analysis of the UNOS database was performed for all cardiac
      transplants performed in patients aged 0-18 yr, with donors classified as to
      whether they received CPR (CPR+) or not (CPR-). We compared overall survival and
      survival at 30 days, one yr, and five yr between groups. Within the CPR+ group,
      the impact of duration of CPR on survival was compared. The need for inotropic
      support and ejection fraction was compared between donor groups as a measure of
      organ function. Overall survival and survival at 30 days, one yr, and five yr did
      not differ in the CPR+ compared to the CPR- group. Within the CPR+ group,
      duration of CPR was unrelated to post-transplant survival. The need for inotropic
      support at procurement was similar, and ejection fraction did not differ between
      the CPR+ and CPR- groups. Donor CPR does not have a negative impact on pediatric
      heart transplant survival.

PMID- 21883749
TI  - Genotype, phenotype, and outcomes of nine patients with T-B+NK+ SCID.
AB  - There are few reports of clinical presentation, genotype, and HCT outcomes for
      patients with T-B+NK+ SCID. Between 1981 and 2007, eight of 84 patients with SCID
      who received and/or were followed after HCT at UCSF had the T-B+NK+ phenotype.
      One additional patient with T-B+NK+ SCID was identified as the sibling of a
      patient treated at UCSF. Chart reviews were performed. Molecular analyses of
      IL7R, IL2RG, JAK3, and the genes encoding the CD3 T-cell receptor components
      delta (CD3D), epsilon (CD3E), and zeta (CD3Z) were carried out. IL7R mutations
      were documented in four patients and CD3D mutations in two others. Three patients
      had no defects found. Only two of nine patients had an HLA-matched related HCT
      donor. Both survived, and neither developed GVHD. Five of seven recipients of
      haploidentical grafts survived. Although the majority of reported cases of T
      B+NK+ SCID are caused by defects in IL7R, CD3 complex defects were also found in
      this series and should be considered when evaluating patients with T-B+NK+ SCID.
      Additional genes, mutations in which account for T-B+NK+ SCID, remain to be
      found. Better approaches to early diagnosis and HCT treatment are needed for
      patients lacking an HLA-matched related donor.

PMID- 21883751
TI  - Calcineurin inhibitor minimization using sirolimus leads to improved renal
      function in pediatric heart transplant recipients.
AB  - The introduction of cyclosporine revolutionized the practice of immunosuppression
      for solid organ transplant recipients, and has resulted in a significant increase
      in survival. While CNI use has been the mainstay of immunosuppressive therapy in
      pediatric heart transplantation, CNIs have been associated with an increased risk
      of nephropathy leading to significant morbidity and mortality. We evaluated the
      effect on renal function of a CNI minimization protocol using SRL in pediatric
      heart transplant patients with CNI induced renal insufficiency. An IRB approved
      retrospective chart review and case control study was performed. There were 20
      patients identified with renal insufficiency who had been converted to SRL
      (target 5-8 ng/mL) and cyclosporine (target 50-75 vs. 125-150 ng/mL). Renal
      insufficiency was defined as isotopic (Indium 111 DTPA) GFR <60 mL/min per 1.73
      m(2) or sCr >1 mg/dL. Outcome variables evaluated were GFR and sCr at time of
      conversion and at two yr post conversion. Comparison was made with case control
      subjects matched for age at Tx, time from Tx to conversion, and initial GFR. The
      median age at Tx = 81 days (S.D. +/-26), median time of conversion after Tx = 10
      yrs (s.d. +/-0.65). Self-limited/treatable side effects included
      hypercholesterolemia (10), neutropenia (6), aphthous ulcer (3), edema (2), anemia
      (2), and tremor (1). One patient rejected in the two yr prior to conversion, and
      one patient had two rejection episodes following conversion. GFR at conversion
      for study group was 51 +/- 14 vs. 60 +/- 2 at two yr, p = 0.018. GFR at inclusion
      for control group was 56 +/- 20 vs. 53 +/- 21, p = 0.253. This report
      demonstrates that minimizing CNI exposure by addition of SRL to the
      immunosuppressant regimen in pediatric heart transplant recipients result in
      improved renal function in comparison to historically managed patients.
      Furthermore, immunotherapy with SRL and lower-dose CNI can effectively prevent
      rejection with an acceptable side-effect profile.

PMID- 21883752
TI  - The impact of age at transfer from pediatric to adult-oriented care on renal
      allograft survival.
AB  - Immaturity among individuals transferred from pediatric to adult-oriented care at
      a young age may leave them vulnerable to higher graft failure risks than in
      individuals transferred older. We sought to determine the impact of age at
      transfer on renal allograft failure rates. We evaluated graft failure rates among
      440 kidney recipients recorded in the UNOS database (1987-2007), who had been
      transferred from pediatric to adult care. Transfers were identified using the
      center codes recorded at yearly data collection. Failure rates for those
      transferred early (<21 yr old) were compared with rates for those transferred
      late (>=21 yr old); time-dependent Cox models were used to estimate the
      additional risk of graft failure associated with early vs. late transfer. The age
      standardized failure rate was 12.9 per 100 person-years among those transferred
      early, and 8.7 per 100 person-years among those transferred late. Compared with
      individuals the same age who had transferred late, graft failure rates were 58%
      higher ([95% confidence interval: 7%, 134%], p = 0.02) among those who had
      transferred early. Younger age at transfer to adult care is associated with
      higher graft failure rates. Transfer to adult-oriented care at <21 yr of age
      should be undertaken with caution.

PMID- 21883753
TI  - Intraindividual variability of the modified Schwartz and novel CKiD GFR equations
      in pediatric renal transplant patients.
AB  - GFR in children can be obtained from a formula using SCr and height or various
      formulas including serum CysC. Recently, two new GFR formulas have been
      developed: (i) height and SCr-mSchwartz GFR and (ii) height, SCr, CysC, and serum
      urea (CKiD GFR). While these formulas proved to be accurate when compared to the
      gold standard, their use in children post-kidney Tx is yet to be assessed. A
      total of 1174 blood samples (urea, SCr and CysC) were analyzed from the post-Tx
      period in 24 Tx children (12 boys, median age = 8.6 yr) currently followed at our
      institution. CKiD GFR and mSchwartz GFR were compared using Bland-Altman analysis
      and the CV. The mSchwartz GFR overestimated the CKiD GFR (mean bias = 1.09 +/-
      0.14; 95% limits of agreements from 0.82 to 1.36). Median CV of CKiD GFR (10.3%)
      was significantly lower than that of mSchwartz GFR (15.0%), p = 0.04, and
      negatively correlated with the slope of GFR (r(2) = 0.34, p = 0.0026). In
      conclusion, CKiD GFR has a significantly lower intraindividual variation than
      mSchwartz GFR and may be better suited for longitudinal follow-up of patients
      post-Tx.

PMID- 21883754
TI  - Colocolonic intussusception in a four-yr-old with a heart transplant: a case
      report and review of the literature.
AB  - A rare case of a colocolonic intussusception in a pediatric cardiac transplant
      patient is reported along with a review of colocolonic intussusception in
      pediatric patients after organ transplantation. A four-yr-old girl with a history
      of heart transplantation shortly after birth presented with a 12-hour history of
      abdominal pain, vomiting, and bloody stools. Initial abdominal x-ray showed
      rectal edema. A rectal examination revealed a palpable intussusceptum that
      prompted a therapeutic contrast enema, which failed to reduce the
      intussusception. Surgical exploration was performed with reduction of the
      intussusception and resection of the terminal ileum and cecum. A pathologic lead
      point was not identified.

PMID- 21883755
TI  - Lethal human herpesvirus-6 encephalitis after cord blood transplant.
AB  - Clinical, biological, pathological, and imaging findings were all suggestive of
      lethal human herpesvirus-6-associated encephalitis in a 61-year-old man who had
      undergone a cord blood transplant. The neuropathological findings of this unusual
      autopsy case and the pathogenesis of this infection in immunocompromised patients
      are discussed.

PMID- 21883756
TI  - Epididymal and prostatic histoplasmosis in a renal transplant recipient from
      southern India.
AB  - An unusual case of epididymal and prostatic histoplasmosis is reported from
      Karnataka State of southern India, in a 37-year-old male renal transplant
      recipient, who had presented with gastrointestinal histoplasmosis a year before
      the second presentation and had responded successfully to 9 months' treatment
      with itraconazole. The patient presented a second time with high-grade fever and
      pain in the scrotum and the lower abdomen. Ultrasound of the abdomen revealed a
      retrotrigonal abscess, which was confirmed on computed tomography scan of the
      pelvis. Pus was drained via transrectal route and biopsy specimens were taken
      from the epididymis and the prostate. Histopathology revealed the picture
      suggestive of histoplasmosis, and the pus on culture confirmed the infection with
      Histoplasma capsulatum. To our knowledge, only 5 cases of epididymal
      histoplasmosis have been reported in the literature, our case being the second
      report from India and sixth in the world; prostatic histoplasmosis is also a rare
      occurrence.

PMID- 21883757
TI  - The association between cytomegalovirus immune globulin and long-term recipient
      and graft survival following liver transplantation.
AB  - The association between cytomegalovirus (CMV) immune globulin (CMVIG) and long
      term clinical outcomes has not been well defined. We examined the association
      between CMVIG and long-term recipient and graft survival in liver transplant
      recipients. Data were from the Scientific Registry of Transplant Recipients and
      included recipients transplanted between January 1995 and October 2008; follow-up
      was through March 2009. All recipients<=80 years of age with primary, single
      organ liver transplants, given CMVIG with (n=2350) or without antivirals (n=455),
      antivirals without CMVIG (n = 32,939), or no CMV prophylaxis (n=28,508) before
      discharge were included. Kaplan-Meier analysis was used to examine rates of acute
      rejection (AR), graft loss, and death, over 7 years post transplantation. The
      adjusted risk of AR, graft loss, and death associated with CMVIG with and without
      antivirals vs. no prophylaxis was estimated using the Cox proportional hazards
      regression. In the univariate analysis, CMVIG, with and without antivirals, was
      associated with increased AR rates, but decreased mortality; CMVIG with
      antivirals was also associated with decreased graft loss compared with no
      prophylaxis. From the multivariable model, CMVIG with antivirals was associated
      with increased risk for AR, but decreased risk for graft loss and death; after
      adjustment, the association between CMVIG alone and mortality was not
      significant. CMVIG with antivirals is associated with increased risk of AR but
      greater long-term patient and graft survival after liver transplantation.

PMID- 21883758
TI  - Immune response after rabies vaccine in a kidney transplant recipient.
AB  - A 48-year-old male kidney-transplant recipient was bitten by a rabid dog. His
      immunosuppressive treatment consisted of cyclosporine 60 mg b.i.d., mycophenolate
      mofetil (MMF) 250 mg t.i.d., and prednisone 5 mg. After wound care, he received 5
      doses of purified vero cell rabies vaccine on days 0, 3, 7, 14, and 28, and human
      rabies immunoglobulin, according to international guidelines. Adequate levels of
      rabies virus neutralizing antibodies were observed after the administration of
      the third vaccine dose. However, a decrease of antibody titer was detected by day
      28. Immunosuppressive medication was minimized, withdrawing MMF and reducing the
      dose of cyclosporine. Booster doses of the same vaccine were administered on days
      38, 41, 45, 52, and 66. Adequate neutralizing antibody response was recovered
      during the ensuing 12 months, under reduced immunosuppression. Nineteen months
      after the incident, the patient remains with good graft function and is
      asymptomatic for rabies. It remains to be determined whether the attained immune
      response was either the result of the booster vaccinations or the reduction of
      immunosuppression alone. Nevertheless, such an outcome would have been possible
      only with the combined management strategy implemented.

PMID- 21883759
TI  - Use of the QuantiFERON-TB Gold interferon-gamma release assay for screening
      transplant candidates: a single-center retrospective study.
AB  - BACKGROUND: Tuberculosis (TB) reactivation is a rare but significant complication
      of organ transplantation, and screening of all transplant candidates for latent
      infection is recommended with either an interferon-gamma release assay (IGRA) or
      tuberculin skin test (TST). METHODS: After institutional review board approval,
      we retrospectively collected data to describe the yield of transplant candidate
      screening using the QuantiFERON-TB Gold (QFT) and QuantiFERON-TB Gold In-Tube
      (QFT-IT) assays since the institution of TB screening in 2008 and the
      epidemiology of all cases of post-transplant TB in our institution since 2004.
      RESULTS: A total of 2392 patients were screened with either the QFT or QFT-IT
      assay through October 2009; 245 (10.2%) tested positive and 206 (8.6%) were
      indeterminate. Of those with positive results, 107 (43.7%) were foreign born and
      most of the remainder had prior TB exposures. Of the tests performed at a
      reference lab, 29% were indeterminate, whereas 14% were indeterminate using our
      in-house lab. The majority of indeterminate results were seen in liver transplant
      candidates (40.6% vs. 11.8% in non-liver candidates). Three of 694 (0.43%)
      screened patients who underwent transplantation developed TB post transplant.
      CONCLUSIONS: Post-transplant TB occurs at a low rate with universal IGRA-based
      candidate screening, which is comparable to studies using TST screening.

PMID- 21883760
TI  - Pseudomonas aeruginosa endocarditis in renal transplant recipients.
AB  - Infective endocarditis (IE) is a serious and life-threatening disease. Transplant
      recipients are at increased risk of acquiring serious infections. The most common
      organisms causing IE in solid organ transplant recipients are reported to be gram
      positive. IE due to Gram-negative organism has rarely been reported. We report 2
      cases of renal transplant recipients who met the Duke's criteria for IE due to
      Pseudomonas aeruginosa.

PMID- 21883761
TI  - Spatial guidance of cell asymmetry: septin GTPases show the way.
AB  - Eukaryotic cells develop asymmetric shapes suited for specific physiological
      functions. Morphogenesis of polarized domains and structures requires the
      amplification of molecular asymmetries by scaffold proteins and regulatory
      feedback loops. Small monomeric GTPases signal polarity, but how their downstream
      effectors and targets are spatially co-ordinated to break cell symmetry is poorly
      understood. Septins comprise a novel family of GTPases that polymerize into non
      polar filamentous structures which scaffold and restrict protein localization.
      Recent studies show that septins demarcate distinct plasma membrane domains and
      cytoskeletal tracks, enabling the formation of intracellular asymmetries. Here,
      we review these findings and discuss emerging mechanisms by which septins promote
      cell asymmetry in fungi and animals.

PMID- 21883762
TI  - Ubiquitination of substrates by esterification.
AB  - Post-translational modification by ubiquitination determines intracellular
      location and fate of numerous proteins, thus impacting a diverse array of
      physiologic functions. Past dogma has been that ubiquitin was only coupled to
      substrates by isopeptide bonds to internal lysine residues or less frequently
      peptide bonds to the N-terminus. Enigmatically, however, several proteins lacking
      lysines had been reported to retain ubiquitin-dependent fates. Resolution of this
      paradox was afforded by recent observations that ubiquitination of substrates can
      also occur on cysteine or serine and threonine residues by thio- or oxy-ester
      bond formation, respectively (collectively called esterification). Although
      chemically possible, these bonds were considered too labile to be of
      physiological relevance. In this review we discuss recent evidence for the
      ubiquitination of protein substrates by esterification and speculate on its
      mechanism and its physiological importance.

PMID- 21883763
TI  - Aminopeptidase-resistant peptides are targeted to lysosomes and subsequently
      degraded.
AB  - Most cytoplasmic and nuclear proteins are degraded via the ubiquitin-proteasome
      system into peptides, which are subsequently hydrolyzed by downstream
      aminopeptidases. Inefficient degradation can lead to accumulation of protein
      fragments, and subsequent aggregation and toxicity. Whereas the role of the
      proteasome and the effect of its impairment on aggregation have been intensively
      studied, little is known about how cells deal with peptides that show resistance
      to degradation by aminopeptidases. Here, we introduced peptidase-resistant
      peptides into living cells and show that these peptides rapidly and irreversibly
      accumulate into puncta in the perinuclear region of the cell. Accumulation
      appears to be independent of peptide sequence but is less efficient for longer
      peptides. The puncta colocalize with autophagosomal and lysosomal markers,
      suggesting that these peptides end up within lysosomes via macroautophagy.
      Surprisingly, the peptides still accumulate within lysosomes when macroautophagy
      is impaired, suggesting a trafficking route independent of macroautophagy. Upon
      lysosomal uptake, peptides are degraded, suggesting that cells can clear
      peptidase-resistant proteasomal products by an alternative pathway, which targets
      them to lysosomes.

PMID- 21883764
TI  - Phagocytosis of IgG-coated polystyrene beads by macrophages induces and requires
      high membrane order.
AB  - The biochemical composition and biophysical properties of cell membranes are
      hypothesized to affect cellular processes such as phagocytosis. Here, we examined
      the plasma membranes of murine macrophage cell lines during the early stages of
      uptake of immunoglobulin G (IgG)-coated polystyrene particles. We found that the
      plasma membrane undergoes rapid actin-independent condensation to form highly
      ordered phagosomal membranes, the biophysical hallmark of lipid rafts.
      Surprisingly, these membranes are depleted of cholesterol and enriched in
      sphingomyelin and ceramide. Inhibition of sphingomyelinase activity impairs
      membrane condensation, F-actin accumulation at phagocytic cups and particle
      uptake. Switching phagosomal membranes to a cholesterol-rich environment had no
      effect on membrane condensation and the rate of phagocytosis. In contrast,
      preventing membrane condensation with the oxysterol 7-ketocholesterol, even in
      the presence of ceramide, blocked F-actin dissociation from nascent phagosomes
      and particle uptake. In conclusion, our results suggest that ordered membranes
      function to co-ordinate F-actin remodelling and that the biophysical properties
      of phagosomal membranes are essential for phagocytosis.

PMID- 21883765
TI  - Hotspots organize clathrin-mediated endocytosis by efficient recruitment and
      retention of nucleating resources.
AB  - The formation of clathrin-coated pits (CCPs) at the plasma membrane has been
      reported to sometimes occur repeatedly at predefined sites. However, defining
      such CCP 'hotspots' structurally and mechanistically has been difficult due to
      the dynamic and heterogeneous nature of CCPs. Here, we explore the molecular
      requirements for hotspots using a global assay of CCP dynamics. Our data
      confirmed that a subset of CCPs is nucleated at spatially distinct sites. The
      degree of clustering of nucleation events at these sites is dependent on the
      integrity of cortical actin, and the availability of certain resources, including
      the adaptor protein AP-2 and the phospholipid PI(4,5)P(2) . We observe that
      modulation in the expression level of FCHo1 and 2, which have been reported to
      initiate CCPs, affects only the number of nucleations. Modulation in the
      expression levels of other accessory proteins, such as SNX9, affects the spatial
      clustering of CCPs but not the number of nucleations. On the basis of these
      findings, we distinguish two classes of accessory proteins in clathrin-mediated
      endocytosis (CME): nucleation factors and nucleation organizers. Finally, we
      observe that clustering of transferrin receptors spatially randomizes pit
      nucleation and thus reduces the role of hotspots. On the basis of these data, we
      propose that hotspots are specialized cortical actin patches that organize CCP
      nucleations from within the cell by more efficient recruitment and/or retention
      of the resources required for CCP nucleation partially due to the action of
      nucleation organizers.

PMID- 21883766
TI  - Rac1 and calmodulin interactions modulate dynamics of ARF6-dependent endocytosis.
AB  - The main cellular Ca(2+)  sensor, calmodulin (CaM), interacts with and regulates
      several small GTPases, including Rac1. The present study revealed high binding
      affinity of Rac1 for CaM and uncovered two new essential binding domains in Rac1:
      the polybasic region, important for phosphatidylinositol-4-phosphate 5-kinase
      (PIP5K) interaction, and the adjacent prenyl group. CaM inhibition increased Rac1
      binding to PIP5K and induced an extensive phosphatidylinositol 4,5-bisphosphate
      (PI4,5P(2) )-positive tubular membrane network. Immunofluorescence demonstrated
      that the tubules were plasma membrane invaginations resulting from an ADP
      ribosylation factor 6 (ARF6)-dependent and clathrin-independent pathway. The role
      of Rac1 in this endocytic route was analyzed by expressing constitutively active
      and inactive mutants. While active Rac1 impaired tubulation, the inactive mutant
      enhanced it. Intriguingly, inactive mutant expression elicited tubulation by
      recruiting PIP5K and inhibiting Rac1 at the plasma membrane. Accordingly, CaM
      inhibition inactivated Rac1 and increased Rac1/PIP5K interaction. Therefore, our
      findings highlight an important new role for Rac1 and CaM in controlling clathrin
      independent endocytosis.

PMID- 21883767
TI  - Development of the Brief Bedside Dysphagia Screening Test in the Czech Republic.
AB  - In patients who are prone to impaired swallowing, dysphagia screening has been
      advocated. However, most dysphagia screening tests are lacking gold-standard
      validation and nurse screeners. The purpose of this study was to develop a
      nursing dysphagia screening test to determine the penetration or aspiration risk
      in patients with neurological and ear, nose, and throat conditions. Eighty-seven
      Czech patients underwent a bedside assessment by nurse screeners. A comparison of
      the results to the gold standard, flexible endoscopic examination of swallowing,
      identified eight "important" or "marginal" assessment items, which were combined
      into one test, called the Brief Bedside Dysphagia Screening Test: "ability to
      clench the teeth"; "symmetry/strength of the tongue"; "symmetry/strength of the
      facial muscles"; "symmetry/strength of the shoulder shrug"; "dysarthria"; "thick
      liquid: choking"; "thick liquid: dripping from the mouth"; and "thick liquid:
      cough". The sensitivity, specificity, and negative predictive value of the Brief
      Bedside Dysphagia Screening Test were: 87.1%, 30.4%, and 81%, respectively, in
      all patients; 95.2%, 27.5%, and 93.3%, respectively, in patients with
      neurological conditions; and 60%, 60%, and 42.9%, respectively, in patients with
      ear, nose, and throat conditions. The test is more suitable for patients with
      neurological conditions than for more heterogeneous patient populations.

PMID- 21883768
TI  - Patients' understandings and feelings of safety during hospitalization in Iran: a
      qualitative study.
AB  - The purpose of this study was to explore patients' understandings and feelings of
      safety during hospitalization. A qualitative design using a thematic analysis
      approach was used to gather and analyze the understandings of 19 patients (11
      male and 8 female) hospitalized in medical and surgical wards of a teaching
      hospital in an urban area of Iran. After employing purposive sampling for the
      selection of participants, semistructured interviews were held for data
      collection. Three main themes emerged from the data analysis: from attention to
      recovery, becoming hopeful of life, and maintaining life routines. The second
      theme consisted of two subthemes: not to be forgotten and becoming optimistic
      toward health-care settings. Supporting mechanisms designed to improve the
      feeling of safety in hospitalized patients should consider the patient as a whole
      and emphasize the humanistic aspect of patient care. In addition we conclude that
      nurses need to learn to assume a leadership role in patient safety.

PMID- 21883769
TI  - Development of the Holistic Nursing Competence Scale.
AB  - This study developed a scale to measure the nursing competence of Japanese
      registered nurses and to test its psychometric properties. Following the
      derivation of scale items and pilot testing, the final version of the scale was
      administered to 331 nurses to establish its internal consistency, as well as its
      construct and criterion-related validity. Using an exploratory and a confirmatory
      factor analysis, 36 items with a five-factor structure were retained to form the
      Holistic Nursing Competence Scale. These factors illustrate nurses' general
      aptitude and their competencies in staff education and management, ethical
      practice, the provision of nursing care, and professional development. The Scale
      has a positive correlation with the length of clinical experience. A Cronbach's
      alpha coefficient was 0.967. The Scale is a reliable and valid measure, helping
      both nurses and organizations to correctly evaluate nurses' competence and
      identify their needs for professional development.

PMID- 21883770
TI  - Biocompatibility and retinal support of a foldable capsular vitreous body
      injected with saline or silicone oil implanted in rabbit eyes.
AB  - INTRODUCTION: The aim of this study was to evaluate over a 180-day period the
      biocompatibility and retinal support of a foldable capsular vitreous body
      injected with either saline or silicone oil implanted in rabbit eyes. METHODS: A
      standard three-port pars plana vitrectomy was performed, and foldable capsular
      vitreous bodies were implanted into the vitreous cavity of rabbit eyes (n = 18).
      Silicone oil tamponade was used as the control group (n = 5). Of the foldable
      capsular vitreous body-implanted eyes, either saline (n = 9) or silicone oil (n =
      9) was injected into the foldable capsular vitreous body to support the retina.
      The treated eyes were examined using a slit lamp with a non-contact slit-lamp
      lens, a tonopen, a non-contact specular microscope and a B-scan ultrasound during
      the 180-day implantation period. A histological examination was performed at 90
      and 180 days. RESULTS: During the 180-day implantation period, no significant
      corneal keratopathy or intraocular inflammation was noted, and the intraocular
      pressure (IOP) and corneal endothelial numbers remained steady among the three
      groups. B-scan ultrasonography showed a smoothly increased echogenicity in front
      of the retina in group of foldable capsular vitreous bodies injected with saline.
      Gross examination showed that the foldable capsular vitreous bodies injected with
      saline or silicone oil smoothly supported the retina. The saline or silicone oil
      inside the foldable capsular vitreous body was homogeneous, transparent and
      filled the foldable capsular vitreous body. Histological examination showed no
      obvious abnormality of the cornea, ciliary body or retina in the foldable
      capsular vitreous body-implanted eyes. CONCLUSIONS: These results suggest that
      foldable capsular vitreous bodies injected with either saline or silicone oil
      showed good biocompatibility and retinal support in rabbit eyes over a 180-day
      implantation time.

PMID- 21883771
TI  - Differential effect of long versus short wavelength light exposure on pupillary
      re-dilation in patients with outer retinal disease.
AB  - BACKGROUND: In patients with outer retinal degeneration, a differential pupil
      response to long wavelength (red) versus short wavelength (blue) light
      stimulation has been previously observed. The goal of this study was to quantify
      differences in the pupillary re-dilation following exposure to red versus blue
      light in patients with outer retinal disease and compare them with patients with
      optic neuropathy and with healthy subjects. DESIGN: Prospective comparative
      cohort study. PARTICIPANTS: Twenty-three patients with outer retinal disease, 13
      patients with optic neuropathy and 14 normal subjects. METHODS: Subjects were
      tested using continuous red and blue light stimulation at three intensities (1,
      10 and 100 cd/m2) for 13 s per intensity. Pupillary re-dilation dynamics
      following the brightest intensity was analysed and compared between the three
      groups. MAIN OUTCOME MEASURES: The parameters of pupil re-dilation used in this
      study were: time to recover 90% of baseline size; mean pupil size at early and
      late phases of re-dilation; and differential re-dilation time for blue versus red
      light. RESULTS: Patients with outer retinal disease showed a pupil that tended to
      stay smaller after light termination and thus had a longer time to recovery. The
      differential re-dilation time was significantly greater in patients with outer
      retinal disease (median = 28.0 s, P < 0.0001) compared with controls and patients
      with optic neuropathy. CONCLUSIONS: A differential response of pupil re-dilation
      following red versus blue light stimulation is present in patients with outer
      retinal disease but is not found in normal eyes or among patients with visual
      loss from optic neuropathy.

PMID- 21883772
TI  - Does unintentional macular translocation after retinal detachment repair
      influence visual outcome?
AB  - BACKGROUND: To document the occurrence of postoperative macular translocation
      after retinal detachment repair and discuss its influence on visual outcome.
      DESIGN: Retrospective case series in a tertiary care setting. PARTICIPANTS: Five
      eyes of five patients presenting to our clinic with macula-off rhegmatogenous
      retinal detachment. METHODS: All patients underwent surgical repair of the
      retinal detachment, with regular postoperative follow-up, including macular
      optical coherence tomography and fundus autofluorescence. MAIN OUTCOME MEASURES:
      Visual acuity and subjective visual symptoms in patients with anatomically
      successful retinal detachment repair, in whom inadvertent macular translocation
      was noted. RESULTS: Our series demonstrates the presence of unintentional macular
      translocation after retinal detachment repair, detected by fundus
      autofluorescence imaging. In contrast to previous reports, we document
      inadvertent macular translocation in one patient after scleral buckling surgery.
      In each case, the retina was fully reattached postoperatively and no other
      complications were identified. There was variability in the symptoms and
      objective visual outcomes after surgery. CONCLUSIONS: Inadvertent macular
      translocation can occur following repair of macula-off retinal detachment, and
      may be a significant contributor to poorer visual outcome after retinal
      detachment, despite objective surgical success.

PMID- 21883773
TI  - Small interfering RNA targeting for infected-cell polypeptide 4 inhibits herpes
      simplex virus type 1 replication in retinal pigment epithelial cells.
AB  - BACKGROUND: This study sought to inhibit herpes simplex virus type 1 replication
      using small interfering RNA which targeting infected-cell polypeptide 4 genes to
      mediate transcription of early and late viral genes in herpes simplex virus type
      1 lytic (productive) infection in retina epithelial cells. METHODS: After pre- or
      post-infecting with herpes simplex virus type 1, small interfering RNAs were
      transfected into retina epithelial cells. The antiviral effects of small
      interfering RNA were evaluated by Western blot, plaque assays, indirect
      immunofluorescence and reverse transcription polymerase chain reaction. The viral
      titre was detected by the 50% tissue culture infective dose method. RESULTS:
      Small interfering RNA decreased infected-cell polypeptide 4 expression in retina
      epithelial cells that were infected with herpes simplex virus type 1 before or
      after small interfering RNA transfection. Compared with herpes simplex virus type
      1 infection alone or transfection with negative control small interfering RNA,
      the viral titre and the retina epithelial cell cytopathic effect were
      significantly decreased in retina epithelial cells transfected with infected-cell
      polypeptide 4-targeting small interfering RNA (50 and 100nM) (P<0.05). The small
      interfering RNA effectively silenced herpes simplex virus type 1 infected-cell
      polypeptide 4 expression on both mRNA and the protein levels (P<0.05). The
      inhibition of infected-cell polypeptide 4-targeting small interfering RNA on
      infected-cell polypeptide 4 protein expression was also verified by Western blot
      in herpes simplex virus type 1 infected human cornea epithelial cell, human
      trabecular meshwork cells and Vero cells. CONCLUSIONS:   Infected-cell
      polypeptide 4-targeting small interfering RNA can inhibit herpes simplex virus
      type 1 replication in retina epithelial cells, providing a foundation for
      development of RNA interference as an antiviral therapy.

PMID- 21883774
TI  - Comparison of intraocular pressure measurement between rebound, non-contact and
      Goldmann applanation tonometry in treated glaucoma patients.
AB  - BACKGROUND: To compare the intraocular pressure readings obtained with the iCare
      rebound tonometer and the 7CR non-contact tonometer with those measured by
      Goldmann applanation tonometry in treated glaucoma patients. DESIGN: A
      prospective, cross-sectional study was conducted in a private tertiary glaucoma
      clinic. PARTICIPANTS OR SAMPLES: One hundred nine (54 males : 55 females)
      patients including only eyes under medical treatment for glaucoma. METHODS:
      Measurement by Goldmann applanation tonometry, iCare rebound tonometry and 7CR
      non-contact tonometry. MAIN OUTCOME MEASURES: Intraocular pressure. RESULTS:
      There were strong correlations between the intraocular pressure measurements
      obtained with Goldmann and both the rebound and non-contact tonometers (Spearman
      r-values >= 0.79, P < 0.001). However, there were small, statistically
      significant differences between the average readings for each tonometer. For the
      rebound tonometer, the mean intraocular pressure was slightly higher compared
      with the Goldmann applanation tonometer in the right eyes (P = 0.02), and similar
      in the left eyes (P = 0.93); however, these differences did not reach statistical
      significance. The Goldmann correlated measurements from the non-contact tonometer
      were lower than the average Goldmann reading for both right (P < 0.001) and left
      (P > 0.01) eyes. The corneal compensated measurements from the non-contact
      tonometer were significantly higher compared with the other tonometers (P <=
      0.001). CONCLUSIONS: The iCare rebound tonometer and the 7CR non-contact
      tonometer measure intraocular pressure in fundamentally different ways to the
      Goldmann applanation tonometer. The resulting intraocular pressure values vary
      between the instruments and will need to be considered when comparing clinical
      versus home acquired measurements.

PMID- 21883775
TI  - Prospective analysis of visual outcomes using apodized, diffractive multifocal
      intraocular lenses following phacoemulsification for cataract or clear lens
      extraction.
AB  - BACKGROUND: To evaluate efficacy, safety and predictability of apodized,
      diffractive multifocal intraocular lenses. DESIGN: Prospective, observational
      study. PARTICIPANTS OR SAMPLE: Two hundred three patients (363 eyes) underwent
      surgery for cataract (54.8%) or clear lens extraction (45.2%). METHODS: A study
      of consecutive patients undergoing lens extraction with insertion of the AcrySof
      Natural ReSTOR intraocular lens (SN60D3). Assessment included: refraction,
      corneal topography, biometry, monocular and binocular uncorrected and best
      spectacle corrected distance and near visual acuity. MAIN OUTCOME MEASURES:
      Visual acuity, spectacle dependence. RESULTS: Mean preoperative best corrected
      visual acuity was 6/12 (cataract) and 6/6 (clear lens extraction). One hundred
      sixty-one (98.2%) of the clear lens extraction group were hyperopic and
      presbyopic (mean spherical equivalent +4.25+/-3.5D). Postoperatively uncorrected
      visual acuity was >=6/12 in 96.5% of eyes (51.9% >=6/6) and >= N5 in 95% of eyes.
      At 6 months, 182 eyes (91.4%) (cataract) and 137 eyes (83.5%) (clear lens
      extraction) were <=0.50 D of target spherical equivalent. Spectacle independence
      was reported in 81.9% (n=168). Minor halos or other visual phenomena were
      reported in 10.2%. No subjects required intraocular lens exchange. Safety index
      at 6 months was 2.5 and 1.17 for cataract and clear lens extraction,
      respectively. CONCLUSIONS: The apodized, diffractive multifocal intraocular lens
      predictably provided excellent near uncorrected visual acuity and good distance
      uncorrected visual acuity following cataract and clear lens extraction surgery
      with a high rate of spectacle independence. A minority of subjects note halos and
      other visual phenomena that may be related to intraocular lens design.

PMID- 21883776
TI  - Prevalence of trachoma in a single community, 1975-2007.
AB  - BACKGROUND: To determine the change in the prevalence in active trachoma in
      children in a remote Aboriginal community over a 32-year period. DESIGN:   Data
      used from two cross-sectional studies repeated in the same community 32 years
      apart. PARTICIPANTS OR SAMPLES: Children aged 5-13 years living in the community.
      METHODS: Thirty-five mm photographs of the everted upper lid taken in 1975 and
      digital photographs taken in 2007 were graded using a fine trachoma-grading
      scheme. MAIN OUTCOME MEASURE: The age-specific prevalence and severity of
      trachoma was compared at the two time points. RESULTS: Images were available from
      82 children in 1975 and from 92 children in 2007. The overall prevalence of
      active trachoma (trachomatous inflammation follicular and or trachomatous
      inflammation intense) was 59% in 1975 and in 2007 was significantly lower at 23%
      (P<0.001). The overall severity grades of active trachoma had also decreased
      significantly for each sign from 1975 to 2007 (all P values from the rank-sum
      test were less than 0.001). However, in 2007, there were still some children with
      severe active trachoma and severe scarring still occurred. CONCLUSION: Although
      the prevalence and severity of active trachoma in children have decreased
      significantly over the last 30 years in this community, trachoma still remains a
      significant public health problem. One third of the children have active
      trachoma, a figure in excess of the threshold set as a public health problem by
      the World Health Organization.

PMID- 21883777
TI  - Tight orbit syndrome resulting from large globe with high myopia: intractable
      glaucoma treated by orbital decompression.

PMID- 21883778
TI  - Referral of diabetic macular oedema by Australian optometrists: comment.

PMID- 21883779
TI  - Perioperative management of the hypothalamic-pituitary-adrenal axis in patients
      with pituitary adenomas: an Australasian survey.
AB  - BACKGROUND: There is limited consensus regarding optimal glucocorticoid
      administration for pituitary surgery to prevent a potential adrenal crisis. AIM:
      To assess the investigation and management of the hypothalamic-pituitary-adrenal
      (HPA) axis in patients undergoing trans-sphenoidal hypophysectomy in Australasia.
      METHODS: A questionnaire was sent to one endocrinologist at each of 18 centres
      performing pituitary surgery in Australasia. Using hypothetical case vignettes,
      respondents were asked to describe their investigation and management of the HPA
      axis for a patient with a: non-functioning macroadenoma and intact HPA axis, non
      functioning macroadenoma and HPA deficiency and growth hormone secreting
      microadenoma undergoing trans-sphenoidal hypophysectomy. RESULTS: Responses were
      received from all 18 centres. Seventeen centres assess the HPA axis
      preoperatively by measuring early morning cortisol or a short synacthen test.
      Preoperative evaluation of the HPA status influenced glucocorticoid prescription
      by 10 centres, including 2/18 who would not prescribe perioperative
      glucocorticoids for a patient with a macroadenoma and an intact HPA axis. Tumour
      size influenced glucocorticoid prescribing patterns at 7/18 centres who prescribe
      a lower dose or no glucocorticoids for a patient with a microadenoma. Choice of
      investigations for definitive postoperative assessment of the HPA axis varied
      with eight centres requesting an insulin tolerance test, four centres a 250 ug
      short synacthen test and six centres requesting other tests. CONCLUSIONS: There
      is wide variability in the investigation and management of perioperative
      glucocorticoid requirements for patients undergoing pituitary surgery in
      Australasia. This may reflect limited evidence to define optimal management and
      that further well-designed studies are needed.

PMID- 21883780
TI  - Patterns of inflammatory activation associated with precipitants of acute
      coronary syndromes: a case-crossover study.
AB  - AIMS: We sought to assess a broad array of possible precipitants of acute
      coronary syndromes (ACS) and evaluate their association with detectable
      inflammatory activation. METHODS AND RESULTS: Within a case-crossover design,
      using a standardised questionnaire, interviews among 348 ST-elevation myocardial
      infarction (44%) or high-risk non-ST-elevation ACS patients (56%), explored
      potential precipitants, including: infection (INF)-temperature >38 degrees C
      and/or respiratory tract, urinary or skin infection; inflammation (INFL)
      exacerbation of inflammatory conditions; exercise (EX)-moderate to heavy
      exercise; fast food (FF)-consumption of a meal purchased from a fast food
      company. Risk and control periods were: weekly over 8 weeks for INF and INFL; 24
      hourly over 4 days for FF and 4 hourly over 48 h for EX. C-reactive protein (CRP)
      levels were assessed at admission. These precipitants were identified in 203/348
      (58.3%) patients. An increased temporal risk was observed for: INF (0-7 days vs 7
      8 weeks odds ratio (OR): 7.5, confidence interval (CI): 1.7-67.6, P = 0.002);
      INFL (0-7 days vs 7-8 weeks OR: 14.0, CI: 2.13-591.9, P = 0.001); EX (0-4 h vs 24
      28 h OR: 2.2, CI: 1.3-3.5, P = 0.001) and FF (0-24 h vs 72-96 h OR: 5.67, CI: 1.6
      30.2, P = 0.003). CRP levels were significantly elevated among patients reporting
      infective and inflammatory potential precipitants, but not among those reporting
      fast food consumption and unaccustomed moderate-heavy exercise. CONCLUSION:
      Infection, inflammatory conditions, moderate-heavy exercise and potentially fast
      food consumption appear to precipitate high-risk ACS. Increased inflammation as
      measured by CRP was not consistently detected despite the identification of an
      ACS precipitant. Strategies that target improved overall health may also lead to
      fewer ACS events through a reduction in triggers.

PMID- 21883781
TI  - Angiotensin-converting enzyme gene insertion/deletion polymorphism and essential
      hypertension in the Chinese population: a meta-analysis including 21,058
      participants.
AB  - BACKGROUND: The angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D)
      polymorphism has been suggested to influence susceptibility to essential
      hypertension (EH), but the results of many individual studies are conflicting.
      AIM AND METHODS: To explore the relationship between the ACE gene I/D
      polymorphism and EH in the Chinese population, 67 separated studies were analyzed
      in a meta-analysis including 21,058 participants. The electronic databases
      PubMed, Embase, Web of Science, China Biological Medicine Database and China
      National Knowledge Infrastructure were searched. The pooled odds ratio (ORs) and
      its corresponding 95% confidence interval were calculated by the random effects
      model. RESULTS: In this ACE I/D gene polymorphism meta-analysis, the distribution
      of the D allele frequency was 0.45 for the EH group and 0.40 for the control
      group. The summary OR for the distribution frequency of D allele was 1.27 (5%
      confidence interval 1.17-1.37). The heterogeneity among the 67 studies was also
      significant (P < 0.00001, I(2) = 71.4%). There was a significant association
      between distribution frequency of the D allele and EH risk in Han, Kazakh,
      Tibetan, Zhuang and unclassified nationalities (P < 0.05). In contrast, in the
      national minorities, such as Mongolian, Uigur, Yi, Dongxiang, Yugu, Korean and
      Gamel, the association between distribution frequency of the D allele and EH risk
      was not significant (P > 0.05). CONCLUSIONS: In the whole Chinese population, the
      D allele was significantly linked with EH susceptibility. However, the relation
      between the I/D polymorphism and EH is still inconclusive in some national
      minorities and must await larger scale studies.

PMID- 21883782
TI  - Preliminary analysis of the cost-effectiveness of the National Bowel Cancer
      Screening Program: demonstrating the potential value of comprehensive real world
      data.
AB  - BACKGROUND/AIM: The complexity and cost of treating cancer patients is escalating
      rapidly and increasingly difficult decisions are being made regarding which
      interventions provide value for money. BioGrid Australia supports collection and
      analysis of comprehensive treatment and outcome data across multiple sites. Here,
      we use preliminary data regarding the National Bowel Cancer Screening Program
      (NBCSP) and stage-specific treatment costs for colorectal cancer (CRC) to
      demonstrate the potential value of real world data for cost-effectiveness
      analyses (CEA). METHODS: Data regarding the impact of NBCSP on stage at diagnosis
      were combined with stage-specific CRC treatment costs and existing literature. An
      incremental CEA was undertaken from a government healthcare perspective,
      comparing NBCSP with no screening. The 2008 invited population (n= 681,915) was
      modelled in both scenarios. Effectiveness was expressed as CRC-related life years
      saved (LYS). Costs and benefits were discounted at 3% per annum. RESULTS: Over
      the lifetime and relative to no screening, NBCSP was predicted to save 1265 life
      years, prevent 225 CRC cases and cost an additional $48.3 million, equivalent to
      a cost-effectiveness ratio of $38,217 per LYS. A scenario analysis assuming full
      participation improved this to $23,395. CONCLUSIONS: This preliminary CEA based
      largely on contemporary real world data suggests population-based faecal occult
      blood test screening for CRC is attractive. Planned ongoing data collection will
      enable repeated analyses over time, using the same methodology in the same
      patient populations, permitting an accurate analysis of the impact of new
      therapies and changing practice. Similar CEA using real world data related to
      other disease types and interventions appears desirable.

PMID- 21883783
TI  - General practitioners' knowledge of and attitudes to inflammatory bowel disease.
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a chronic disease requiring long
      term management. General practitioners (GPs) are often the first point of contact
      for initial symptoms and flares. Thus we assessed GPs' attitudes to and knowledge
      of IBD. METHODS: A state-wide postal survey of GPs was performed collecting
      demographic details, practice and attitudes in IBD-specific management and
      knowledge. RESULTS: Of 1800 GPs surveyed in South Australia, 409 responded; 58%
      were male, 80% Australian trained and 73% practised in metropolitan areas. Most
      GPs (92%) reported seeing zero to five IBD patients per month. Overall, 37% of
      the GPs reported being generally 'uncomfortable' with IBD management.
      Specifically, they were only somewhat comfortable in providing/using maintenance
      therapy, steroid therapy or unspecified therapy for an acute flare. They were
      uncomfortable with the use of immunomodulators and biologicals (71 and 91%
      respectively). No GP reported never referring, referring sometimes (12%), often
      (34%) or always (55%). Most (87%) GPs rated their communication with private
      specialists positively; while only 32% were satisfied with support from public
      hospitals. Of concern, most (70%) monitored patients on immunosuppression on a
      case-by-case basis rather than by protocol. In multivariable analyses, GPs' IBD
      specific knowledge did not influence comfort with overall management, nor did
      knowledge influence GP comfort with any particular therapy. CONCLUSION:
      Individual GPs care for few IBD patients and have variable attitudes in their
      practice. Whether improvement can realistically be achieved given individual GP's
      paucity of patients is questionable. These data support the provision of better
      support and specific action plans for IBD patients.

PMID- 21883784
TI  - Homozygous FCGR3A-158V alleles predispose to late onset neutropenia after CHOP-R
      for diffuse large B-cell lymphoma.
AB  - BACKGROUND: Recent reports suggest genetic polymorphisms influence susceptibility
      to rituximab-induced late-onset neutropenia (LON), which in turn may be a
      predictor of good outcome in B-cell lymphoma. AIMS: We report the largest study
      to date assessing FCGR3A-V158F polymorphisms in diffuse large B-cell lymphoma
      (DLBCL) treated with cyclophosphamide/hydroxydaunorubicin/Oncovin
      (vincristine)/prednisone/rituximab (CHOP-R). The influence of C1qA-A276G
      polymorphisms in DLBCL, and the impact of both polymorphisms on susceptibility to
      LON and outcome were also examined. METHODS: 115 DLBCL patients treated with CHOP
      R were compared with 105 healthy White people controls with regards to FCGR3A
      V158F and C1qA-A276G polymorphisms. LON incidence and event-free and overall
      survival (EFS and OS) were analysed for linkage to either polymorphism. RESULTS:
      The FCGR3A-V158F but not the C1qA-A276G polymorphism influenced the risk of
      developing LON. 50% of FCGR3A-158V/V patients experienced LON. In contrast, only
      7% V/F and 2% F/F experienced LON. The FCGR3A-158V/V genotype was associated with
      LON compared with V/F (P = 0.028) and F/F genotypes (P = 0.005). Although no
      patients with either LON or FCGR3A-158V homozygosity relapsed compared with 33%
      FCGR3A-158F/F and 21% non-LON, this did not translate into improved EFS or OS.
      CONCLUSIONS: Polymorphic analysis may be a predictive tool to identify those at
      high risk of LON. Prospective studies are required to establish definitively if
      LON or FCGR3A-158V/V genotype influences outcome.

PMID- 21883785
TI  - Encouraging results in older patients receiving chemotherapy: a retrospective
      analysis of treatment guideline adherence in daily practice.
AB  - OBJECTIVE: A retrospective study was performed to determine whether patients over
      60 years old who received chemotherapy were treated according to the existing
      treatment guidelines and to investigate the reasons for dose reductions or
      treatment delay. MATERIAL AND METHODS: Three hundred and seven patients aged over
      60 years old and diagnosed with colon, breast or lung cancer between 1998 and
      2008 who were treated with chemotherapy in the Radboud University Medical Center
      were included. From the medical records we recorded the number of and the reasons
      for dose reductions and delays. We calculated the relative dose intensity (RDI)
      received. RESULTS: RDI did not decrease significantly with age. However patients
      over 65 years of age had a higher probability of receiving a suboptimal dose
      intensity, even when treated with curative intent. There was no correlation
      between toxicity and age, however the comorbidity score increased with age. The
      average received RDI was higher in patients diagnosed more recently. CONCLUSION:
      Despite increased comorbidity, older patients receiving chemotherapy were
      generally treated according to protocol without high incidence of severe
      toxicity. We saw improvement of RDI over the time period investigated. The
      participation of geriatricians in multidisciplinary oncology teams could help to
      optimize therapy decisions for patients with comorbidity.

PMID- 21883786
TI  - Associations of muscle stiffness and thickness with muscle strength and muscle
      power in elderly women.
AB  - AIM: The aims of this study were to investigate the influence of age on muscle
      stiffness and to examine the relationships among muscle stiffness, muscle
      thickness, subcutaneous fat thickness, muscle strength and muscle power in
      elderly women. METHODS: The subjects were 16 young (mean age 20.3 years) and 34
      elderly (mean age 84.2 years) women. Muscle stiffness of the right quadriceps
      femoris muscle was measured at rest and during a maximal voluntary isometric
      muscle contraction using a myotonometer, a computerized, electronic tissue
      compliance meter. Thicknesses of the rectus femoris and the vastus intermedius
      muscles and the overlying subcutaneous fat were measured using ultrasound.
      Quadriceps strength and the chair stand test were used to represent muscle
      strength and muscle power, respectively. RESULTS: There were significant
      differences in muscle stiffness between rest and contraction conditions among the
      young but not the elderly women. Muscle stiffness during contraction, the rate of
      change in muscle stiffness during contraction, and muscle thickness were
      significantly greater in young than in elderly subjects. Pearson correlation
      coefficient analyses showed that muscle stiffness was significantly associated
      with muscle power, but not with muscle strength. CONCLUSION: This study suggests
      that the increase in muscle stiffness during voluntary muscle contraction is
      limited in elderly women compared with young women, and that muscle stiffness may
      be related to muscle power rather than muscle strength in elderly persons.

PMID- 21883787
TI  - Arabinoxylans and inulin differentially modulate the mucosal and luminal gut
      microbiota and mucin-degradation in humanized rats.
AB  - The endogenous gut microbiota affects the host in many ways. Prebiotics should
      favour beneficial intestinal microbes and thus improve host health. In this
      study, we investigated how a novel class of potential prebiotic long-chain
      arabinoxylans (LC-AX) and the well-established prebiotic inulin (IN) modulate the
      gut microbiota of humanized rats. Six weeks after axenic rats were inoculated
      with a human faecal microbiota, their colonic microbiota was similar to this
      inoculum (~ 70%), whereas their caecal microbiota was enriched with
      Verrucomicrobia and Firmicutes concomitant with lower abundance of Bacteroidetes.
      Moreover, different Bifidobacterium species colonized the lumen (B. adolescentis)
      and mucus (B. longum and B. bifidum). Both LC-AX and IN increased SCFA levels and
      induced a shift from acetate towards health-promoting propionate and butyrate
      respectively. By applying a high-resolution phylogenetic micro-array (HITChip) at
      the site of fermentation (caecum), IN and LC-AX were shown to stimulate bacterial
      groups with known butyrate-producers (Roseburia intestinalis, Eubacterium
      rectale, Anaerostipes caccae) and bifidobacteria (B. longum) respectively.
      Prebiotic administration also resulted in lower caecal abundances of the mucin
      degrading Akkermansia muciniphila and potentially more mucin production by the
      host. Both factors might explain the increased caecal mucin levels for LC-AX
      (threefold) and IN (sixfold). These mucins were degraded along the colon,
      resulting in high faecal abundances of Akkermansia muciniphila for LC-AX and
      especially IN-treated rats. Finally, the microbial changes caused an adaptation
      period for the host with less weight gain, after which the host fine-tuned the
      interaction with this altered microbiota. Our results demonstrate that next to
      IN, LC-AX are promising prebiotic compounds by stimulating production of health
      promoting metabolites by specific microbes in the proximal regions. Further,
      prebiotic supplementation shifted mucin degradation to distal regions, where
      mucin-degraders may produce beneficial metabolites (e.g. propionate by
      Akkermansia muciniphila), so that prebiotics may potentially improve gut health
      along the entire length of the intestine.

PMID- 21883788
TI  - Comparison of biosurfactant detection methods reveals hydrophobic surfactants and
      contact-regulated production.
AB  - Biosurfactants are diverse molecules with numerous biological functions and
      industrial applications. A variety of environments were examined for
      biosurfactant-producing bacteria including soil, water and leaf surfaces.
      Biosurfactant production was assessed with an atomized oil assay for a large
      number of bacterial isolates and compared with a commonly used drop collapse
      assay from broth and plate cultures. The atomized oil assay detected every strain
      that produced a biosurfactant detectable by the drop collapse test, and also
      identified additional strains that were not detected with the drop collapse assay
      because they produced low levels of surfactant or hydrophobic (low water
      solubility) surfactants such as pumilacidins. Not all strains that produced a
      biosurfactant detectable by the drop collapse when cultured on agar surfaces
      produced surfactants detectable by drop collapse when cultured in broth, and vice
      versa. Many bacterial strains exhibited preferential production of surfactants
      when grown on an agar surface compared with broth cultures, and such surface
      enhancement of production could also be stimulated by increasing the viscosity of
      liquid culture media. Surface induction of surfactant production in the epiphyte
      Pseudomonas syringae was regulated at the transcriptional level.

PMID- 21883789
TI  - Assimilation of acetate by the putative atmospheric methane oxidizers belonging
      to the USCalpha clade.
AB  - Forest soils are a major biological sink for atmospheric methane, yet the
      identity and physiology of the microorganisms responsible for this process remain
      unclear. Although members of the upland soil cluster alpha (USCalpha) are assumed
      to represent methanotrophic bacteria adapted to the oxidation of the trace level
      of methane in the atmosphere and to be an important sink of this greenhouse gas,
      so far they have resisted isolation. In particular, the question of whether the
      atmospheric methane oxidizers are able to obtain all their energy and carbon
      solely from atmospheric methane still waits to be answered. In this study, we
      performed stable-isotope probing (SIP) of RNA and DNA to investigate the
      assimilation of (13) C-methane and (13) C-acetate by USCalpha in an acidic forest
      soil. RNA-SIP showed that pmoA mRNA of USCalpha was not labelled by (13) C of
      supplemented (13) C methane, although catalysed reporter deposition -
      fluorescence in situ hybridization (CARD-FISH) targeting pmoA mRNA of USCalpha
      detected its expression in the incubated soil. In contrast, incorporation of (13)
      C-acetate into USCalphapmoA mRNA was observed. USCalphapmoA genes were not
      labelled, indicating that they had not grown during the incubation. Our results
      indicate that the contribution of alternative carbon sources, such as acetate, to
      the metabolism of the putative atmospheric methane oxidizers in upland forest
      soils might be substantial.

PMID- 21883790
TI  - Engineering multiple genomic deletions in Gram-negative bacteria: analysis of the
      multi-resistant antibiotic profile of Pseudomonas putida KT2440.
AB  - The genome of the soil bacterium Pseudomonas putida strain KT2440 has been erased
      of various determinants of resistance to antibiotics encoded in its extant
      chromosome. To this end, we employed a coherent genetic platform that allowed the
      precise deletion of multiple genomic segments in a large variety of Gram-negative
      bacteria including (but not limited to) P. putida. The method is based on the
      obligatory recombination between free-ended homologous DNA sequences that are
      released as linear fragments generated upon the cleavage of the chromosome with
      unique I-SceI sites, added to the segment of interest by the vector system.
      Despite the potential for a SOS response brought about by the appearance of
      double stranded DNA breaks during the process, fluctuation experiments revealed
      that the procedure did not increase mutation rates - perhaps due to the
      protection exerted by I-SceI bound to the otherwise naked DNA termini. With this
      tool in hand we made sequential deletions of genes mexC, mexE, ttgA and ampC in
      the genome of the target bacterium, orthologues of which are known to determine
      various degrees of antibiotic resistance in diverse microorganisms. Inspection of
      the corresponding phenotypes demonstrated that the efflux pump encoded by ttgA
      sufficed to endow P. putida with a high-level of tolerance to beta-lactams,
      chloramphenicol and quinolones, but had little effect on, e.g. aminoglycosides.
      Analysis of the mutants revealed also a considerable diversity in the
      manifestation of the resistance phenotype within the population and suggested a
      degree of synergism between different pumps. The directed edition of the P.
      putida chromosome shown here not only enhances the amenability of this bacterium
      to deep genomic engineering, but also validates the corresponding approach for
      similar handlings of a large variety of Gram-negative microorganisms.

PMID- 21883791
TI  - Iron transporters in marine prokaryotic genomes and metagenomes.
AB  - In the pelagic environment, iron is a scarce but essential micronutrient. The
      iron acquisition capabilities of selected marine bacteria have been investigated,
      but the recent proliferation of marine prokaryotic genomes and metagenomes offers
      a more comprehensive picture of microbial iron uptake pathways in the ocean.
      Searching these data sets, we were able to identify uptake mechanisms for Fe(3+),
      Fe(2+) and iron chelates (e.g. siderophore and haem iron complexes). Transport of
      iron chelates is accomplished by TonB-dependent transporters (TBDTs). After
      clustering the TBDTs from marine prokaryotic genomes, we identified TBDT clusters
      for the transport of hydroxamate and catecholate siderophore iron complexes and
      haem using gene neighbourhood analysis and co-clustering of TBDTs of known
      function. The genomes also contained two classes of siderophore biosynthesis
      genes: NRPS (non-ribosomal peptide synthase) genes and NIS (NRPS Independent
      Siderophore) genes. The most common iron transporters, in both the genomes and
      metagenomes, were Fe(3+) ABC transporters. Iron uptake-related TBDTs and
      siderophore biosynthesis genes were less common in pelagic marine metagenomes
      relative to the genomic data set, in part because Pelagibacter ubique and
      Prochlorococcus species, which almost entirely lacked these Fe uptake systems,
      dominate the metagenomes. Our results are largely consistent with current
      knowledge of iron speciation in the ocean, but suggest that in certain niches the
      ability to acquire siderophores and/or haem iron chelates is beneficial.

PMID- 21883792
TI  - Distribution and growth of aerobic anoxygenic phototrophs in the Mediterranean
      Sea.
AB  - The distribution of aerobic anoxygenic phototrophs (AAPs) was surveyed in various
      regions of the Mediterranean Sea in spring and summer. These phototrophic
      bacteria were present within the euphotic layer at all sampled stations. The AAP
      abundances increased with increasing trophic status ranging from 2.5 * 10(3)
      cells per ml in oligotrophic Eastern Mediterranean up to 90 * 10(3) cells per ml
      in the Bay of Villefranche. Aerobic anoxygenic phototrophs made up on average 1
      4% of total prokaryotes in low nutrient areas, whereas in coastal and more
      productive stations these organisms represented 3-11% of total prokaryotes. Diel
      bacteriochlorophyll a decay measurements showed that AAP community in the Western
      Mediterranean grew rapidly, at rates from 1.13 to 1.42 day(-1). The lower AAP
      abundances registered in the most oligotrophic waters suggest that they are
      relatively poor competitors under nutrient limiting conditions. Instead, AAPs
      appear to be metabolically active organisms, which thrive better in more
      eutrophic environments providing the necessary substrates to maintain high growth
      rates.

PMID- 21883793
TI  - Prevalence of season-specific Escherichia coli strains in the Yeongsan River
      Basin of South Korea.
AB  - Seasonal and spatial variation in the genotypic richness of 3480 Escherichia coli
      isolates obtained from the Yeongsan River basin in South Korea was investigated
      by using the horizontal fluorophore-enhanced rep-PCR (HFERP) DNA fingerprinting
      technique. The relationship between 60 E. coli isolates from each of 58
      freshwater samples was determined by using multidimensional scaling (MDS)
      analysis and self-organized maps (SOMs). The MDS analysis, done based on HFERP
      DNA fingerprints, showed that E. coli isolates obtained in October through
      December clustered tightly, while those obtained in other sampling periods were
      more genetically diverse. However, site-specific E. coli genotypes were not
      observed. SOMs analysis, done using the 10 most frequently isolated E. coli
      genotypes, showed the occurrence of season-specific E. coli genotypes and the
      main SOMs clusters were most influenced by temperature, strain diversity and
      biochemical oxygen demand. Diversity among E. coli genotypes tended to decrease
      as water temperature decreased, and the numbers of E. coli genotypes observed in
      urban area were greater, more diverse and less dependent on water temperature
      than those obtained from agricultural areas. Taken together, our findings
      indicate that that an ecological approach needs to be considered in order to
      obtain a better understanding of E. coli community dynamics in the environment
      and that SOMs analysis is useful to visualize the multidimensional dependent
      variables that are influencing the types and dynamics of specific E. coli
      genotypes in the environment.

PMID- 21883794
TI  - Identification and analysis of the gene cluster involved in biosynthesis of
      paenibactin, a catecholate siderophore produced by Paenibacillus elgii B69.
AB  - Bacteria belonging to the genus Paenibacillus are recognized as rich sources of
      bioactive natural products. To date, there are few characterized siderophores
      from this genus. Here, through genome analysis, we identified a non-ribosomal
      peptide biosynthetic gene cluster (pae) responsible for siderophore assembly in
      Paenibacillus elgii B69. The 12.8 kb gene cluster comprises six open reading
      frames encoding proteins similar to the components of the bacillibactin
      biosynthetic machinery and bacillibactin esterase. To examine the product of the
      pae gene cluster, we cultured P. elgii B69 in iron-deficient medium for
      siderophore expression. A novel siderophore structurally similar to
      bacillibactin, designated paenibactin, was purified and characterized. Its
      structure was determined as a cyclic trimeric lactone of 2,3-dihydroxybenzoyl
      alanine-threonine. The involvement of the pae gene cluster in paenibactin
      biosynthesis was confirmed by the biochemical assay of adenylation domain
      specificity. Furthermore, we demonstrated that the pae gene cluster evolves from
      an ancestral bacillibactin biosynthetic gene cluster via sequence and
      phylogenetic analyses. The structural difference between paenibactin and
      bacillibactin may stem from a mutation-induced change in the adenylation domain
      specificity. Based on these findings and published models for bacillibactin, we
      proposed models for paenibactin biosynthesis, ferric-paenibactin uptake and
      paenibactin-bounded iron release.

PMID- 21883795
TI  - Resistance, resilience and recovery: aquatic bacterial dynamics after water
      column disturbance.
AB  - For lake microbes, water column mixing acts as a disturbance because it
      homogenizes thermal and chemical gradients known to define the distributions of
      microbial taxa. Our first objective was to isolate hypothesized drivers of lake
      bacterial response to water column mixing. To accomplish this, we designed an
      enclosure experiment with three treatments to independently test key
      biogeochemical changes induced by mixing: oxygen addition to the hypolimnion,
      nutrient addition to the epilimnion, and full water column mixing. We used
      molecular fingerprinting to observe bacterial community dynamics in the treatment
      and control enclosures, and in ambient lake water. We found that oxygen and
      nutrient amendments simulated the physical-chemical water column environment
      following mixing and resulted in similar bacterial communities to the mixing
      treatment, affirming that these were important drivers of community change. These
      results demonstrate that specific environmental changes can replicate broad
      disturbance effects on microbial communities. Our second objective was to
      characterize bacterial community stability by quantifying community resistance,
      recovery and resilience to an episodic disturbance. The communities in the
      nutrient and oxygen amendments changed quickly (had low resistance), but
      generally matched the control composition by the 10th day after treatment,
      exhibiting resilience. These results imply that aquatic bacterial assemblages are
      generally stable in the face of disturbance.

PMID- 21883797
TI  - Differential decay of human faecal Bacteroides in marine and freshwater.
AB  - Genetic markers from Bacteroides and other faecal bacteria are being tested for
      inclusion in regulations to quantify aquatic faecal contamination and estimate
      public health risk. For the method to be used quantitatively across environments,
      persistence and decay of markers must be understood. We measured concentrations
      of contaminant molecular markers targeting Enterococcus and Bacteroides spp. in
      marine and freshwater microcosms spiked with human sewage and exposed to either
      sunlight or dark treatments. We used Bayesian statistics with a delayed Chick
      Watson model to estimate kinetic parameters for target decay. DNA- and RNA-based
      targets decayed at approximately the same rate. Molecular markers persisted
      (could be detected) longer in marine water. Sunlight increased the decay rates of
      cultured indicators more than those of molecular markers; sunlight also limited
      persistence of molecular markers. Within each treatment, Bacteroides markers had
      similar decay profiles, but some Bacteroides markers significantly differed in
      decay rates. The role of extracellular DNA in persistence appeared unimportant in
      the microcosms. Because conditions were controlled, microcosms allowed the
      effects of specific environmental variables on marker persistence and decay to be
      measured. While marker decay profiles in more complex environments would be
      expected to vary from those observed here, the differences we measured suggest
      that water matrix is an important factor affecting quantitative source tracking
      and microbial risk assessment applications.

PMID- 21883798
TI  - Colonization of cucumber seeds by bacteria during germination.
AB  - Detailed analysis revealed fundamental differences between bacterial association
      with cucumber (Cucumis sativus) seeds and seedlings roots. Seed colonization by
      bacteria seems to result from passive encounter between bacteria, conveyed by
      imbibed soil solution, and the germinating seed. In accordance, the seed
      associated bacterial community composition directly reflected that of the
      germination medium and was characterized by low dominance. Transition from seed
      to root was marked by a shift in bacterial community composition and in an
      increase in dominance values. Furthermore, settlement of bacteria on roots was
      tightly controlled by the specific properties of each root segment. Size and
      richness of the seed-associated bacterial community were clearly determinate by
      the community in the germination medium. In contrast, for fully developed and
      active roots, the medium effect on these parameters was negligible. Perturbation
      of the seed environment by a pathogen (Pythium aphanidermatum) had major
      consequences on the seed bacterial community. However, those were mostly related
      to direct pathogen-bacteria rather than seed-bacteria interactions. In
      conclusion, simple, even passive processes may determine the initial stage of
      plant-microbe association during seed germination, prior to extension of the
      primary root. Therefore, seed germination is a unique phase in the plant life
      cycle, with respect to its interaction with the below-ground microbiome.

PMID- 21883799
TI  - Microbial rhodopsins on leaf surfaces of terrestrial plants.
AB  - The above-ground surfaces of terrestrial plants, the phyllosphere, comprise the
      main interface between the terrestrial biosphere and solar radiation. It is
      estimated to host up to 10(26)  microbial cells that may intercept part of the
      photon flux impinging on the leaves. Based on 454-pyrosequencing-generated
      metagenome data, we report on the existence of diverse microbial rhodopsins in
      five distinct phyllospheres from tamarisk (Tamarix nilotica), soybean (Glycine
      max), Arabidopsis (Arabidopsis thaliana), clover (Trifolium repens) and rice
      (Oryza sativa). Our findings, for the first time describing microbial rhodopsins
      from non-aquatic habitats, point towards the potential coexistence of microbial
      rhodopsin-based phototrophy and plant chlorophyll-based photosynthesis, with the
      different pigments absorbing non-overlapping fractions of the light spectrum.

PMID- 21883800
TI  - New roles for bacterial siderophores in metal transport and tolerance.
AB  - Siderophores are chelators with extremely strong affinity for ferric iron and are
      best known for their capacity to feed microorganisms with this metal. Despite
      their preference for iron, they can also chelate numerous other metals with
      variable affinities. There is also increasing evidence that metals other than
      iron can activate the production of siderophores by bacteria, thereby implicating
      siderophores in the homeostasis of metals other than iron and especially heavy
      metal tolerance. This article considers this new concept that siderophores play a
      role in protecting bacteria against metal toxicity and discusses the possible
      contribution of these chelators to the transport of biological relevant metals in
      addition to iron.

PMID- 21883796
TI  - Responses of soil cellulolytic fungal communities to elevated atmospheric CO2 are
      complex and variable across five ecosystems.
AB  - Elevated atmospheric CO(2) generally increases plant productivity and
      subsequently increases the availability of cellulose in soil to microbial
      decomposers. As key cellulose degraders, soil fungi are likely to be one of the
      most impacted and responsive microbial groups to elevated atmospheric CO(2). To
      investigate the impacts of ecosystem type and elevated atmospheric CO(2) on
      cellulolytic fungal communities, we sequenced 10,677 cbhI gene fragments encoding
      the catalytic subunit of cellobiohydrolase I, across five distinct terrestrial
      ecosystem experiments after a decade of exposure to elevated CO(2). The cbhI
      composition of each ecosystem was distinct, as supported by weighted Unifrac
      analyses (all P-values; < 0.001), with few operational taxonomic units (OTUs)
      being shared across ecosystems. Using a 114-member cbhI sequence database
      compiled from known fungi, less than 1% of the environmental sequences could be
      classified at the family level indicating that cellulolytic fungi in situ are
      likely dominated by novel fungi or known fungi that are not yet recognized as
      cellulose degraders. Shifts in fungal cbhI composition and richness that were
      correlated with elevated CO(2) exposure varied across the ecosystems. In aspen
      plantation and desert creosote bush soils, cbhI gene richness was significantly
      higher after exposure to elevated CO(2) (550 umol mol(-1)) than under ambient
      CO(2) (360 umol mol(-1) CO(2)). In contrast, while the richness was not altered,
      the relative abundance of dominant OTUs in desert soil crusts was significantly
      shifted. This suggests that responses are complex, vary across different
      ecosystems and, in at least one case, are OTU-specific. Collectively, our results
      document the complexity of cellulolytic fungal communities in multiple
      terrestrial ecosystems and the variability of their responses to long-term
      exposure to elevated atmospheric CO(2).

PMID- 21883801
TI  - The haem-uptake gene cluster in Vibrio fischeri is regulated by Fur and
      contributes to symbiotic colonization.
AB  - Although it is accepted that bacteria-colonizing host tissues are commonly faced
      with iron-limiting conditions and that pathogenic bacteria often utilize iron
      from host-derived haem-based compounds, the mechanisms of iron acquisition by
      beneficial symbiotic bacteria are less clear. The bacterium Vibrio fischeri
      mutualistically colonizes the light organ of the squid Euprymna scolopes. Genome
      sequence analysis of V. fischeri revealed a putative haem-uptake gene cluster,
      and through mutant analysis we confirmed this cluster is important for haemin use
      by V. fischeri in culture. LacZ reporter assays demonstrated Fur-dependent
      transcriptional regulation of cluster promoter activity in culture. GFP-based
      reporter assays revealed that gene cluster promoter activity is induced in
      symbiotic V. fischeri as early as 14 h post inoculation, although colonization
      assays with the haem uptake mutant suggested an inability to uptake haem does not
      begin to limit colonization until later stages of the symbiosis. Our data
      indicate that the squid light organ is a low iron environment and that haem-based
      sources of iron are used by symbiotic V. fischeri cells. These findings provide
      important additional information on the availability of iron during symbiotic
      colonization of E. scolopes by V. fischeri, as well as the role of haem uptake in
      non-pathogenic host-microbe interactions.

PMID- 21883802
TI  - Biologically threatened dolphins and whales.
AB  - Among the several threats to which free-ranging cetaceans are exposed, a number
      of biological noxae are believed to represent a serious hazard to their health
      and conservation on a global scale, with special emphasis on the Mediterranean
      Sea. These pathogens include viral agents such as Morbillivirus, which during the
      last 25 years have caused dramatic epidemics and die-offs among several aquatic
      mammal species and populations worldwide, as well as Herpesvirus, protozoan
      agents such as Toxoplasma gondii and bacterial pathogens such as Brucella spp.

PMID- 21883804
TI  - Intranasal administration of insulin to the brain impacts cognitive function and
      peripheral metabolism.
AB  - In recent years, the central nervous system (CNS) has emerged as a principal site
      of insulin action. This notion is supported by studies in animals relying on
      intracerebroventricular insulin infusion and by experiments in humans that make
      use of the intranasal pathway of insulin administration to the brain. Employing
      neurobehavioural and metabolic measurements as well as functional imaging
      techniques, these studies have provided insight into a broad range of central and
      peripheral effects of brain insulin. The present review focuses on CNS effects of
      insulin administered via the intranasal route on cognition, in particular memory
      function, and whole-body energy homeostasis including glucose metabolism.
      Furthermore, evidence is reviewed that suggests a pathophysiological role of
      impaired brain insulin signaling in obesity and type 2 diabetes, which are
      hallmarked by peripheral and possibly central nervous insulin resistance, as well
      as in conditions such as Alzheimer's disease where CNS insulin resistance might
      contribute to cognitive dysfunction.

PMID- 21883803
TI  - Elevated AIM2-mediated pyroptosis triggered by hypercytotoxic Francisella mutant
      strains is attributed to increased intracellular bacteriolysis.
AB  - Intracellular bacterial pathogens Francisella novicida and the Live Vaccine
      Strain (LVS) are recognized in the macrophage cytosol by the AIM2 inflammasome,
      which leads to the activation of caspase-1 and the processing and secretion of
      active IL-1beta, IL-18 and pyroptosis. Previous studies have reported that F.
      novicida and LVS mutants in specific genes (e.g. FTT0584, mviN and ripA) induce
      elevated inflammasome activation and hypercytotoxicity in host cells, leading to
      the proposal that F. novicida and LVS may have proteins that actively modulate
      inflammasome activation. However, there has been no direct evidence of such
      inflammasome evasion mechanisms. Here, we demonstrate for the first time that the
      above mutants, along with a wide range of F. novicida hypercytotoxic mutants that
      are deficient for membrane-associated proteins (DeltaFTT0584, DeltamviN,
      DeltaripA, DeltafopA and DeltaFTN1217) or deficient for genes involved in O
      antigen or LPS biosynthesis (DeltawbtA and DeltalpxH) lyse more intracellularly,
      thus activating increased levels of AIM2-dependent pyroptosis and other innate
      immune signalling pathways. This suggests that an inflammasome-specific evasion
      mechanism may not be present in F. novicida and LVS. Furthermore, future studies
      may need to consider increased bacterial lysis as a possible cause of elevated
      stimulation of multiple innate immune pathways when the protein composition or
      surface carbohydrates of the bacterial membrane is altered.

PMID- 21883805
TI  - Do antidiabetic medications play a specific role in differentiated thyroid cancer
      compared to other cancer types?
AB  - The risk for differentiated thyroid cancer, like for many other types of cancer,
      is increased in obese individuals and people with intermediate hyperglycaemia.
      The incidence of all cancers, with the exception of thyroid cancer, is also
      increased in type 2 diabetes mellitus patients. The review compares the
      prevalence of thyroid carcinoma and other cancers in obese, people with
      intermediate hyperglycaemia and patients with diabetes and summarizes mode of
      action and anti-tumourigenic effect of common antidiabetic medications. The over
      expression of dipeptidyl peptidase IV in the tumours, not seen in the other
      cancer types, is suggested as a potential reason for the unique situation in
      thyroid cancer.

PMID- 21883806
TI  - Achieving a clinically relevant composite outcome of an HbA1c of <7% without
      weight gain or hypoglycaemia in type 2 diabetes: a meta-analysis of the
      liraglutide clinical trial programme.
AB  - AIM: Effective type 2 diabetes management requires a multifactorial approach
      extending beyond glycaemic control. Clinical practice guidelines suggest targets
      for HbA1c, blood pressure and lipids, and emphasize weight reduction and avoiding
      hypoglycaemia. The phase 3 clinical trial programme for liraglutide, a human
      glucagon-like peptide 1 analogue, showed significant improvements in HbA1c and
      weight with a low risk of hypoglycaemia compared to other diabetes therapies. In
      this context, we performed a meta-analysis of data from these trials evaluating
      the proportion of patients achieving a clinically relevant composite measure of
      diabetes control consisting of an HbA1c <7% without weight gain or hypoglycaemia.
      METHODS: A prespecified meta-analysis was performed on 26-week patient-level data
      from seven trials (N = 4625) evaluating liraglutide with commonly used therapies
      for type 2 diabetes: glimepiride, rosiglitazone, glargine, exenatide, sitagliptin
      or placebo, adjusting for baseline HbA1c and weight, for a composite outcome of
      HbA1c <7.0%, no weight gain and no hypoglycaemic events. RESULTS: At 26 weeks,
      40% of the liraglutide 1.8 mg group, 32% of the liraglutide 1.2 mg group and 6
      25% of comparators (6% rosiglitazone, 8% glimepiride, 15% glargine, 25%
      exenatide, 11% sitagliptin, 8% placebo) achieved this composite outcome. Odds
      ratios favoured liraglutide 1.8 mg by 2.0- to 10.5-fold over comparators.
      CONCLUSIONS: As assessed by the composite outcome of HbA1c <7%, no hypoglycaemia
      and no weight gain, liraglutide was clearly superior to the other commonly used
      therapies. However, the long-term clinical impact of this observation remains to
      be shown.

PMID- 21883807
TI  - Your patient information website: how good is it?
AB  - AIM: The study was designed to evaluate the accessibility, reliability and
      readability of information on familial adenomatous polyposis (FAP) on the Web.
      METHOD: We searched for the keywords 'familial adenomatous polyposis' using the
      three most popular search engines (GoogleTM YahooTM, MSNTM) and looked at the
      first 50 websites. The LIDA tool (an online validation instrument for healthcare
      websites) was used to assess their accessibility, usability and reliability. The
      readability of each document was assessed using the Flesch Reading Ease (FRE)
      score. We also checked whether each site was certified by the Health on the Net
      Foundation Code of Conduct (HONcode)--the oldest and most trustworthy code for
      medical and health-related information available on the Internet. RESULTS: Of the
      150 possible sites, only 48 were analysed because of repetitions (52), irrelevant
      content (21) or inaccessible links (29). Nineteen were HONcode-certified. The
      mean LIDA and FRE scores for all websites were 62.59% (SD=10) and 32.9 (SD=16)
      respectively. HONcode-certified websites have slightly higher reliability scores
      than HONcode-uncertified websites (38.5%vs 36.2%). CONCLUSION: Good quality
      information on patients with FAP is difficult to obtain on the Internet. The
      websites analysed have alarmingly low reliability scores. The readability of
      their content is poor and they often do not appear among the top search results.
      There is a need to develop a clear, easily accessible and authoritative resource
      for patients with FAP.

PMID- 21883808
TI  - Distal intestinal obstruction syndrome in an adult with cystic fibrosis.

PMID- 21883809
TI  - Life threatening haemorrhage after electrode removal: a severe complication
      following sacral nerve stimulation procedure for the treatment of faecal
      incontinence.

PMID- 21883810
TI  - Dome-type colorectal carcinoma: a case report and review of the literature.

PMID- 21883811
TI  - Effect of the laxative magnesium oxide on gastrointestinal functional recovery in
      fast-track colonic resection: a double-blind, placebo-controlled randomized
      study.
AB  - AIM: A double-blind randomized controlled study was conducted to compare the
      effect of magnesium oxide (1 g 12-h) with placebo given within an evidence-based
      multimodal rehabilitation programme on gastrointestinal recovery, pain,
      mobilization and hospital stay after open colonic resection. METHOD: Of 62
      potentially eligible patients, 13 were excluded, leaving 22 in the magnesium
      oxide group and 27 in the placebo group. The main outcome measure was time to
      normalization of bowel function. Secondary outcome measures included
      postoperative nausea, vomiting, pain, fatigue, mobilization and length of
      postoperative hospital stay. RESULTS: The median times to first flatus and
      defaecation in the laxative and placebo groups were 18.0 vs 14.0 h and 42 vs 50 h
      (P > 0.15). Early intake of liquids, protein drinks and solid food, nausea and
      vomiting, pain, fatigue and mobilization were similar in the groups (P > 0.3).
      The median postoperative hospital stay was 3 days in both groups (P > 0.65).
      CONCLUSION: Magnesium oxide does not enhance the recovery of gastrointestinal
      function within the context of an evidence-based multimodal rehabilitation
      programme after open colonic surgery.

PMID- 21883812
TI  - Rectal irrigation: a useful tool in the armamentarium for functional bowel
      disorders.
AB  - AIM: The efficacy of rectal irrigation (RI) was assessed in patients with various
      functional bowel disorders. METHOD: A prospective analysis was carried out of
      patients presenting to our functional bowel clinic from 2005 to 2009. The
      Cleveland Clinic Constipation and Incontinence Scores were used to assess
      outcomes following rectal irrigation. Patients were asked if they were satisfied
      with RI and would recommend it to a friend. RESULTS: Ninety-one patients (80
      female, median age 51 (17-78) years had undergone rectal irrigation for the
      following indications: chronic constipation (n = 32), slow transit constipation
      (n = 18), obstructed defaecation (n = 10), and faecal incontinence (n = 31). Of
      the 60 patients with constipation, 50 (83%) were available for follow up. Mean
      constipation scores improved from 18.72 to 11.45 following rectal irrigation (P =
      0.001). Twenty-five patients experienced failure of RI to control symptoms, 10 of
      whom were offered surgery. Of the patients with incontinence, 20 (67%) were
      available for follow up. Mean incontinence scores improved from 16.2 to 10.8 with
      rectal irrigation (P = 0.005). Twelve patients discontinued RI, the commonest
      reason being lack of improvement in symptoms. Seven of these patients were
      offered surgery. The only complication was in one patient with constipation who
      had minor rectal bleeding following irrigation, which was stopped. CONCLUSION:
      Rectal irrigation can be a useful tool in the management of functional bowel
      disorders and should be tried prior to the consideration of any surgery. However,
      further work is needed to define the precise indications and patient selection
      criteria.

PMID- 21883813
TI  - Risk factors for surgical site infection after elective resection for rectal
      cancer. A multivariate analysis on 2131 patients.
AB  - AIM: Surgical site infection (SSI) is the most common cause of morbidity after
      colorectal surgery. The aim of this study was to analyze risk factors for SSI in
      patients who had undergone surgery for rectal cancer. METHOD: A multicentre
      observational study was carried out on 2131 patients operated on for rectal
      cancer between May 2006 and May 2009. Twenty-nine centres were involved. SSI
      included wound infection and organ space infection within 30 days after the
      operation. Univariate and multivariate analyses were carried out to study
      possible risk factors for SSI. RESULTS: Wound infection and organ space infection
      were diagnosed in 8.9% and 10%, respectively, of patients. The anastomotic
      leakage rate was 8%. Multivariate analysis showed that wound infection was
      related to tumour stage, a converted laparoscopic procedure and open surgery.
      Organ space infection was related to Stage IV tumour, a tumour < 11 cm from the
      anal verge, low anterior resection and Hartmann's procedure. CONCLUSION: Rectal
      surgery for malignant disease is associated with a considerable rate of SSI.
      Wound infection and organ space infection are related to different factors and
      therefore should be evaluated separately.

PMID- 21883814
TI  - Functional results and patient satisfaction with sacral nerve stimulation for
      idiopathic faecal incontinence.
AB  - AIM: Sacral nerve stimulation (SNS) is an established treatment for faecal
      incontinence (FI) when conservative modalities have failed to restore continence.
      This two-centre study aimed to document functional outcome and its relationship
      to patient satisfaction. METHOD: Patients treated with SNS for idiopathic FI in
      Aarhus (Denmark) and Maastricht (The Netherlands) were included. At the most
      recent follow-up appointment, 127 patients (80%) were identified as receiving
      active SNS therapy. A questionnaire considering bowel habits, quality of life,
      and self-reported satisfaction and a 3-week bowel-habit diary were mailed to
      these patients, and 85% responded. RESULTS: Patient satisfaction was clearly
      related to the number of FI episodes. Patients experiencing full continence were
      all satisfied, and although the satisfaction rate decreased as the number of FI
      episodes increased, 46% of the patients with more FI episodes at follow-up than
      at baseline were still satisfied. Per-protocol analysis resulted in a
      satisfaction rate of 57.3%. In total, 74.7% of the patients receiving active SNS
      therapy reported a reduction of >= 50% in FI episodes, 10.3% of whom were
      dissatisfied after a median of 46 months of follow-up. CONCLUSION: There is a
      clear relationship between patient satisfaction and improved continence. A total
      of 57.3% of the patients offered SNS therapy were satisfied at follow-up.
      However, 46% of the patients with more FI episodes at follow-up than at baseline
      were also satisfied. Therefore, functional outcome of SNS therapy cannot be based
      only on bowel-habit diaries and bowel scores.

PMID- 21883815
TI  - Demonstration of erectile management techniques to men scheduled for radical
      prostatectomy reduces long-term regret: a comparative cohort study.
AB  - OBJECTIVE: To determine whether preoperative demonstrations of intracavernosal
      and vacuum therapies for erectile dysfunction (ED) influence the decision of
      treatment choice, reducing long-term regret. PATIENTS AND METHODS: In all, 82
      consecutive men with localized prostate cancer, scheduled for radical
      prostatectomy and reporting an International Index of Erectile Function score of
      >21, were prospectively enrolled at a single cancer centre. Following standard
      preoperative counselling, half of the men were invited to attend a further
      consultation for intracavernosal and vacuum therapy demonstrations. All patients
      were evaluated pretreatment and then 3 monthly using the five-point International
      Index of Erectile Function score and the 14-item Hospital Anxiety and Depression
      scale. At 12 months treatment choice changes were recorded and patients were
      assessed for treatment choice regret using Clark's validated two-item regret
      questionnaire. Statistical analysis was performed using the Mann-Whitney and
      Fisher's exact tests. Results were compared with a control population of 41 men
      who did not undergo additional ED counselling. RESULTS: In all, 8/41 men (19%)
      changed their treatment choice, opting for brachytherapy rather than radical
      prostatectomy. Only 1/41 in the control population changed their decision before
      surgery. At 1 year, one patient (2%) in the intervention group expressed regret
      at his treatment choice (radical prostatectomy) compared with eight (20%) in the
      control group (P= 0.03, two-sided Fisher's exact test); ED was identified as the
      major cause of this regret. CONCLUSION: Preoperative demonstrations of ED
      therapies can optimize decision making in prostate cancer and help reduce long
      term regret.

PMID- 21883817
TI  - The burden of bladder cancer in men and women: analysis of the years of life
      lost.
AB  - OBJECTIVE: To estimate the average loss in life expectancy (LE) due to bladder
      cancer (BC) in men and women in the USA. PATIENTS AND METHODS: Cancer records for
      51,528 patients diagnosed with BC during 1988-1997 were obtained from the
      Surveillance, Epidemiology, and End Results database. Potential follow-up ranged
      from 10 to 20 years (median 14 years). Loss in median LE at BC diagnosis was
      computed as the difference between expected median survival and observed median
      survival. Expected survival was calculated using two methods: method 1 used age,
      sex, and race-specific LE in the general population, method 2 used the hazard of
      death from non-BC causes in patients with BC (to account for past exposures and
      treatment-related toxicities not present in the general population). RESULTS:
      During the study period, BC death occurred in 17% of men and 23% of women and non
      BC death occurred in 53% of men and 47% of women. Using LE in the general
      population as the reference (method 1), loss in median LE at BC diagnosis was 3.9
      years for men (33% of their potential remaining years of life) and 6.5 years for
      women (47% of their potential remaining years of life). Using non-BC-specific
      hazard as the reference (method 2), loss in median LE was 2.7 years for men (26%
      of their potential remaining years of life) and 4.1 years for women (36% of their
      potential remaining years of life). CONCLUSION: Compared with men, women loose
      more years of life and a greater fraction of their life expectancy to BC.

PMID- 21883816
TI  - Robot-assisted partial nephrectomy for sporadic ipsilateral multifocal renal
      tumours.
AB  - OBJECTIVE: To report our short-term results of robot-assisted partial nephrectomy
      for treating sporadic multiple ipsilateral renal tumours. METHODS: Over a 3-year
      period, eight patients with two or more ipsilateral renal masses underwent nine
      robotic partial nephrectomies in our institution. We evaluated the PADUA and
      R.E.N.A.L. nephrometry scores, intraoperative outcomes, histopathological
      characteristics, complications according to Clavien classification and renal
      function outcomes. RESULTS: In total, 19 tumours were removed from eight patients
      in nine procedures. Mean operative time was 199 +/- 47 min (median 200; range 150
      300). Mean size of the dominant lesion was 3.0 +/- 1.1 cm (2.7; 1.6-4.8) and
      overall mean tumour size was 2.2 +/- 1.2 cm (1.9; 0.4-4.8). Mean number of
      tumours removed per patient was 2.4. Median PADUA and R.E.N.A.L. scores were 7
      and 6 (with the predominance of an anterior, non-hilar position), respectively.
      Excluding the six off-clamp resected tumours, the mean warm ischaemia time was 21
      +/- 9.2 min (21; 10-35). Mean estimated blood loss was 250 +/- 154 mL (200; 100
      500) and no patient required transfusion. There were no intraoperative
      complications or conversion to open surgery. One patient had atrial fibrillation,
      resolved with anti-arrhythmic drugs. Mean length of stay was 4.2 +/- 0.97 days.
      Sixteen of the nineteen tumours were malignant, most of papillary type and
      Fuhrman grade II. The mean decrease in glomerular filtration rate was 4%, with a
      mean follow-up of 14 months. CONCLUSIONS: Robotic partial nephrectomy for
      sporadic ipsilateral multifocal renal tumours is feasible and safe. Off-clamp
      resection of multiple tumours can also be safely performed in carefully selected
      lesions.

PMID- 21883818
TI  - The role of a standardized 36 core template-assisted transperineal prostate
      biopsy technique in patients with previously negative transrectal ultrasonography
      guided prostate biopsies.
AB  - OBJECTIVE: To determine the efficacy and safety of a standardized 36 core
      template-assisted transperineal biopsy technique for detecting prostate cancer in
      patients with previously negative transrectal ultrasonography-guided prostate
      biopsies and elevated prostate-specific antigen (PSA) levels. PATIENTS AND
      METHODS: Between April 2008 to September 2010, a total of 40 patients with a mean
      (range) age of 63 (49-73) years, a mean (range) elevated PSA level of 21.9 (4.7
      87) ng/mL and two previous sets of negative TRUS-guided prostate biopsies
      underwent standardized 36 core template-assisted transperineal prostate biopsies
      under general anaesthetic as a day case procedure. The cancer detection rate and
      complications for all cases were evaluated. RESULTS: In total, 27 of 40 (68%)
      patients were found to have adenocarcinoma of the prostate, two patients (5.0%)
      had atypical small acinar proliferation, one had high-grade prostatic
      intraepithelial neoplasia (2.5%), four (10%) had chronic active inflammation and
      six (15%) had benign histology. Gleason scores were in the range 6-9, with a
      median Gleason score of 7. There were no cases of urosepsis, urinary tract
      infections or haematuria. A single patient experienced acute urinary retention,
      with a subsequent succesful trial without a catheter, and haematospermia was
      common, although minor. CONCLUSIONS: Our standardized 36 core template-assisted
      transperineal prostate biopsy technique is safe and associated with a high
      detection rate of prostate cancer. This technique should be considered in
      patients with elevated PSA levels and previously negative TRUS-guided prostate
      biopsies.

PMID- 21883819
TI  - Time trends in prostate cancer surgery: data from an Internet-based multicentre
      database.
AB  - OBJECTIVES: To report our experience with an Internet-based multicentre database
      that enables tumour documentation, as well as the collection of quality-related
      parameters and follow-up data, in surgically treated patients with prostate
      cancer. The system was used to assess the quality of prostate cancer surgery and
      to analyze possible time-dependent trends in the quality of care. PATIENTS AND
      METHODS: An Internet-based database system enabled a standardized collection of
      treatment data and clinical findings from the participating urological centres
      for the years 2005-2009. An analysis was performed aiming to evaluate relevant
      patient characteristics (age, pathological tumour stage, preoperative
      International Index of Erectile Function-5 score), intra-operative parameters
      (operating time, percentage of nerve-sparing operations, complication rate,
      transfusion rate, number of resected lymph nodes) and postoperative parameters
      (hospitalization time, re-operation rate, catheter indwelling time). Mean values
      were calculated and compared for each annual cohort from 2005 to 2008. The
      overall survival rate was also calculated for a subgroup of the Berlin patients.
      RESULTS: A total of 914, 1120, 1434 and 1750 patients submitted to radical
      prostatectomy in 2005, 2006, 2007 and 2008 were documented in the database. The
      mean age at the time of surgery remained constant (66 years) during the study
      period. More than half the patients already had erectile dysfunction before
      surgery (median International Index of Erectile Function-5 score of 19-20).
      During the observation period, there was a decrease in the percentage of pT2
      tumours (1% in 2005; 64% in 2008) and a slight increase in the percentage of
      patients with lymph node metastases (8% in 2005; 10% in 2008). No time trend was
      found for the operating time (142-155 min) or the percentage of nerve-sparing
      operations (72-78% in patients without erectile dysfunction). A decreasing
      frequency was observed for the parameters: blood transfusions (1.9% in 2005; 0.5%
      in 2008), postoperative bleeding (2.6%; 1.2%) and re-operations (4.5%; 2.8%). The
      mean hospitalization time decreased accordingly (10 days in 2005; 8 days in
      2008). The examined subcohort had an overall mortality of 1.5% (median follow-up
      of 3 years). CONCLUSIONS: An Internet-based database system for tumour
      documentation in patients with prostate cancer enables the collection and
      assessment of important parameters for the quality of care and outcomes. The
      participating centres show an improvement in the quality of surgical management,
      including a reduction of the complication rate.

PMID- 21883820
TI  - Long-term results of a randomized trial comparing holmium laser enucleation of
      the prostate and transurethral resection of the prostate: results at 7 years.
AB  - OBJECTIVE: To assess the durability of holmium laser enucleation of prostate in
      comparison to transurethral resection of the prostate (TURP). PATIENTS AND
      METHODS: Patients were enrolled in the present study between June 1997 and
      December 2000 and followed per protocol. All patients were urodynamically
      obstructed with a prostate volume of between 40 and 200 mL. At long-term follow
      up, variables assessed included Benign Prostatic Hyperplasia Impact Index
      (BPHII), International Continence Society Short Form Male questionnaire (ICSmale
      SF) and the International Index of Erectile Function (IIEF). Adverse events,
      including the need for retreatment, were specifically assessed. RESULTS: Thirty
      one (14 holmium laser enucleation of the prostate [HoLEP] and 17 TURP) of the
      initial 61 patients were available, with 12 deceased and 18 lost to follow-up.
      The mean (range) follow-up was 7.6 (5.9-10.0) years and the mean (+/-sd) age at
      follow-up was 79.8 (+/-6.2) years. The mean (+/-sd) values (HoLEP vs TURP) were
      as follows: maximum urinary flow rate (Q(max)), 22.09 +/- 15.47 vs 17.83 +/- 8.61
      mL/s; American Urological Association (AUA) symptom score, 8.0 +/- 5.2 vs 10.3 +/
      7.42; quality of life (QOL) score 1.47 +/- 1.31 vs 1.31 +/- 0.85; BPHII, 1.53 +/
      2.9 vs 0.58 +/- 0.79; IIEF-EF (erectile function), 11.6 +/- 7.46 vs 9.21 +/-
      7.17; ICSmale Voiding Score (VS), 4.2 +/- 3.76 vs 3.0 +/- 2.41; ICSmale
      Incontinence Score (IS), 3.07 +/- 3.3 vs 1.17 +/- 1.4. There were no significant
      differences in any variable between the two groups beyond the first year. Of the
      assessable patients, none required re-operation for recurrent BPH in the HoLEP
      arm and three (of 17) required re-operation in the TURP arm . CONCLUSION: The
      results of this randomized trial confirm that HoLEP is at least equivalent to
      TURP in the long term with fewer re-operations being necessary.

PMID- 21883821
TI  - Clinical elicitation of the penilo-cavernosus reflex in circumcised men.
AB  - OBJECTIVE: * To test clinical observations that the penilo-cavernosus reflex is
      much more difficult to elicit in circumcised men. PATIENTS AND METHODS: * Men
      consecutively referred for uro-neurological or uro-neurophysiological examination
      were prospectively included. * Those with possible sacral neuropathic lesions
      were excluded. * A history was obtained, and a clinical neurological examination
      was performed. * The penilo-cavernosus reflex was tested clinically and
      neurophysiologically using electrical and mechanical stimulation. * Reflex
      elicitability scores in groups of circumcised men, men with foreskin retraction
      and a control group of uncircumcised men were compared using the Mann-Whitney U
      test. RESULTS: * The reflex was clinically non-elicitable in 73%, 64% and 8% of
      30 circumcised men, 15 men with foreskin retraction, and 29 control men,
      respectively. * The scored reflex elicitability was significantly (P < 0.001)
      higher in control men than in the other two groups clinically, but not
      neurophysiologically. CONCLUSION: * The study confirmed the lower clinical and
      similar neurophysiological elicitability of the penilo-cavernosus reflex in
      circumcised men and in men with foreskin retraction. This finding needs to be
      taken into account by urologists and other clinicians in daily clinical practice.

PMID- 21883822
TI  - The relationship between Prostate CAncer gene 3 (PCA3) and prostate cancer
      significance.
AB  - OBJECTIVE: To evaluate the relationship between Prostate CAncer gene 3 (PCA3) and
      prostate cancer significance. PATIENTS AND METHODS: Clinical data from two multi
      centre European open-label, prospective studies evaluating the clinical utility
      of the PCA3 assay in guiding initial and repeat biopsy decisions were analysed.
      First-catch urine was collected after digital rectal examination (three strokes
      per lobe) and the PCA3 score was determined using the PROGENSA((r)) PCA3 assay.
      Transrectal ultrasound-guided biopsy (>=8 cores) and radical prostatectomy (RP)
      specimens were analysed by the local pathologist. The relationship between biopsy
      and RP outcomes with the PCA3 score was assessed. RESULTS: Of the 1009 men
      enrolled, 348 (34%) had a positive biopsy. The median and mean PCA3 scores were
      statistically significantly lower in men with biopsy Gleason score <7 vs >=7,
      with clinical stage T1c vs T2a-T2c, T3a cancers, with <=33% vs >33% positive
      biopsy cores and with 'biopsy indolent' vs 'biopsy significant' prostate cancer
      (indolent prostate cancer defined by biopsy Epstein criteria). In all, 175 men
      with a positive biopsy had a RP: median and mean PCA3 scores were statistically
      significantly lower in men with pathological Gleason score <7 vs >=7, and with
      pathological stage T2a-T2c vs T3a-T3b cancers. CONCLUSIONS: The PCA3 score may
      combined with traditional tools aid in identifying men with clinically
      insignificant prostate cancer, as shown by biopsy and RP pathological features
      including biopsy Epstein criteria, who could be candidates for active
      surveillance. Treatment selection should be based on a combination of clinical
      and pathological variables. If one wants to use a threshold point to guide
      treatment decisions in clinical practice, a PCA3 score threshold of 20 may have
      the highest utility for selecting men with clinically insignificant prostate
      cancer in whom active surveillance may be appropriate; a PCA3 score threshold of
      50 may be used to identify men at high risk of harbouring significant prostate
      cancer who are candidates for RP. Although the association between the PCA3 score
      and prostate cancer aggressiveness needs further evaluation, the inclusion of the
      PCA3 score into patient management strategies may provide clinicians with another
      tool to more accurately determine the course of treatment.

PMID- 21883824
TI  - In the era of micro-dissection sperm retrieval (m-TESE) is an isolated testicular
      biopsy necessary in the management of men with non-obstructive azoospermia?
AB  - OBJECTIVES: To assess the outcome of sperm retrieval using micro-dissection-TESE
      (m-TESE) and simultaneous diagnostic biopsy in NOA to determine if the final
      definitive histology correlated with the outcome of sperm retrieval by m-TESE in
      men with NOA. To determine if there was a correlation between FSH levels and
      positive sperm retrieval rates and assessed the success rate of m-TESE as either
      a primary or a salvage procedure after previous negative sperm retrieval. The EAU
      guidelines (2010) recommend that in men with non obstructive azoospermia 'a
      testicular biopsy is the best procedure to define the histological diagnosis and
      the possibility of finding sperm'. However, these guidelines do not identify
      which patients should have a diagnostic biopsy and if this biopsy should be
      performed as an isolated procedure or synchronously with sperm retrieval. It is
      also suggested that there is a correlation between the histological diagnosis and
      possibility of finding sperm on testis biopsy. PATIENTS AND METHODS: 100 men with
      NOA underwent a m-TESE sperm retrieval between 2005 and 2010 at a single centre.
      All patients underwent hormonal analysis (serum FSH, Testosterone and LH levels)
      and genetic analyses after full counselling including; Y-deletion, CF-gene
      analysis and karyotype. Thirty five men had previously undergone unsuccessful
      TESA/TESE or diagnostic biopsy at other centres. All patients underwent
      synchronous sperm retrieval and biopsy of the testis, which was sent for
      histopathological examination on the day of an ICSI cycle or as an isolated
      procedure. RESULTS: Mean age of patients was 37.25 (range 29-56 years). The mean
      serum FSH levels in the Sertoli cell only, maturation arrest and
      hypospermatogenesis groups were 21.3 IU/L (2.8-75), 16.18 (1.6-67) and 14.17 IU/L
      (0.8-42.3) respectively. SR rates in the respective groups were 42.85%, 26.6% and
      75.86% (P= 0.023). There were no post-operative complications. In the 35 men who
      had previously undergone unsuccessful procedures elsewhere, the SR rates were
      57.1%. The overall sperm retrieval rate was 50%. There was no correlation between
      SR and FSH levels (P= 0.28). CONCLUSION: M-TESE should be considered the gold
      standard for retrieval of testicular sperm in NOA, even in cases where there has
      been previously unsuccessful attempts. FSH levels and histology cannot be used to
      predict the success of sperm retrieval. An isolated diagnostic testicular biopsy
      is not recommended in men with NOA, as a significant proportion of men undergoing
      m-TESE will have successful a sperm retrieval irrespective of previous histology
      or previous unsuccessful surgery.

PMID- 21883823
TI  - Pelvic floor disorders: linking genetic risk factors to biochemical changes.
AB  - Pelvic floor disorders (PFDs) such as stress urinary incontinence (SUI) and
      pelvic organ prolapse (POP) may share a common pathophysiological process related
      to pelvic floor tissue laxity and loss of support. We reviewed recent literature
      on observed biochemical changes in women with SUI and POP, linking them to
      genetic predisposition. We found that studies of pelvic tissues showed
      differences between control subjects and women with POP and SUI in collagen and
      elastin structure at a molecular and fibrillar level. Studies were heterogeneous
      but showed a trend towards decreased collagen and elastin content. The
      contribution of matrix metalloproteinases to increased collagenolysis can be
      related to genetic polymorphisms present in higher frequency in women with PFD.
      Extracellular matrix (ECM) protein turnover plays a role in the development of
      POP and SUI, but much remains to be understood of this complex dynamic interplay
      of enzymes, proteins and molecules. Genotyping of candidate genes participating
      in ECM formation will elucidate the missing link between the manifestation of the
      disease and the biochemical changes observed systematically, in addition to those
      in the pelvic floor.

PMID- 21883826
TI  - Prostatic intraepithelial neoplasia: its morphological and molecular diagnosis
      and clinical significance.
AB  - The aim of the present paper was to review the morphological spectrum of
      prostatic intraepithelial neoplasia (PIN), its relationship to carcinoma of the
      prostate (PCa) and its clinical significance. We reviewed the literature on
      premalignant lesions of the prostate, with an emphasis on high grade prostatic
      intraepithelial neoplasia (HGPIN). HGPIN is the most likely precursor of PCa,
      according to almost all available evidence. HGPIN is characterized by cellular
      proliferations within pre-existing ducts and acini, with nuclear and nucleolar
      enlargement similar to PCa. The clinical importance of recognizing HGPIN is based
      on its association with PCa. In recent years, a significant decline from 36% to
      22% in the predictive value of cancer after an initial diagnosis of HGPIN. A
      major factor contributing to the decreased incidence of cancer after a diagnosis
      of HGPIN on needle biopsy in the contemporary era is related to increased needle
      biopsy core sampling, which detects many associated cancers on initial biopsy.
      Some recent studies have suggested that molecular findings associated with HGPIN
      might be able to predict which men are more likely to have cancer on re-biopsy.

PMID- 21883825
TI  - Vitamin D(3)  cryosensitization increases prostate cancer susceptibility to
      cryoablation via mitochondrial-mediated apoptosis and necrosis.
AB  - OBJECTIVES: To investigate the effect and molecular mechanisms of action of
      Vitamin D(3) (VD(3) ) as a neo-adjunctive agent before cryosurgery in an effort
      to increase treatment efficacy for prostate cancer (CaP). To eliminate the
      potential for disease recurrence that exists at the periphery of the freeze
      lesion, where temperatures may be insufficient to destroy both androgen-sensitive
      (AS) and androgen-insensitive (AI) CaP. METHODS: Human CaP cells, LNCaP, were
      each genetically altered to express the AS and AI phenotypes and subjected to
      VD(3) treatment and freezing in an in vitro and tissue-engineered model. Cell
      viability, caspase inhibitor and western blot studies were used to determine the
      basis of the different responses of AI and AS cells to VD(3) cryosensitization.
      RESULTS: VD(3) was found to be a highly effective cryosensitizer, resulting in a
      >50% overall increase in cell death after -15  degrees C freezing. Fluorescence
      microscopy, western blot analysis and caspase protease assays confirmed that the
      increased activation of apoptosis was modulated through a mitochondrial-mediated
      pathway. Caspase inhibition studies showed that apoptosis played an integral role
      in cell death, with VD(3) cryosensitivation-induced apoptotic events responsible
      for >30% of the overall cell death after -15  degrees C freezing. CONCLUSIONS:
      The present study suggests that the use of VD(3) as a cryosensitizer increases
      cryoablation efficacy through the increased activity of apoptosis as well as
      through necrosis. The data show that through VD(3) treatment the overall level of
      AI CaP cell tolerance to freezing is reduced to a level similar to that of AS
      CaP. VD(3) pre-treatment in conjunction with cryoablation may increase treatment
      efficacy and reduce disease recurrence for CaP patients.

PMID- 21883827
TI  - Complications and postoperative events after cryosurgery for prostate cancer.
AB  - OBJECTIVES: There has been a call in the urological literature for standardized
      reporting of complications. To use strict criteria aiming to report our
      complications and other postoperative events in a cohort of men undergoing third
      generation prostate cryosurgery. PATIENTS AND METHODS: Demographic, clinical and
      pathological data were collected on men undergoing primary cryosurgery from 2002
      2010, excluding those who had received neoadjuvant or adjuvant radiotherapy.
      Complications and events were broadly defined as any deviation from the expected
      postoperative course and any subjective complaint expressed during a follow-up
      visit. Descriptive statistics were generated and compared between groups using
      chi-squared and rank sum tests as appropriate. Logistic regression analyses were
      performed to assess the potential predictors of any complication or event.
      RESULTS: In total, 106 consecutive patients were identified.   There were no
      intra-operative complications or instances of equipment failure. We observed 42
      early complications, with 48 delayed and 10 late postoperative events. A total of
      five (4.7%) patients had persistent urge and/or stress incontinence. Thirty-one
      patients had International Prostate Symptom Score (IPSS) and bother index scores
      available before and after surgery; median scores decreased from 7 and 2 to 6 and
      1, for IPSS and bother index, respectively. Twenty-four patients had Sexual
      Health Inventory for Men scores available before surgery and at 2-year follow-up;
      median scores decreased from 11 to 2. On multivariate analysis, there were no
      significant associations. CONCLUSIONS: Modern cryosurgery is safe, and most of
      the complications and postoperative events are transient. Erectile function,
      however, has marked deterioration. We were unable to identify significant risk
      factors for complications or postoperative events.

PMID- 21883828
TI  - Incidence of second malignancies after external beam radiotherapy for clinical
      stage I testicular seminoma.
AB  - OBJECTIVES: * To determine the use of adjuvant external beam radiotherapy (EBRT)
      for patients with clinical stage I testicular seminoma in the USA. * To quantify
      the risk of specific second primary malignancies (SPMs) associated with radiation
      exposure in these patients. PATIENTS AND METHODS: * We used the Surveillance,
      Epidemiology and End Results database to identify patients diagnosed with
      clinical stage I testicular seminoma between 1973 and 2000. * We evaluated the
      use of EBRT in these patients. * We calculated standardized incidence ratios of
      specific SPMs in these patients. * We stratified the incidence of SPMs based on
      age at seminoma diagnosis and time to SPM from initial seminoma diagnosis.
      RESULTS: * Adjuvant EBRT use declined from the first decade of the study period
      to the last decade of the study period (80.6% vs 70.2%). * Overall, there was a
      19% increase in SPMs in patients exposed to EBRT (observed/expected, O/E, 1.51;
      95% CI, 1.08-1.31) compared to the general population. * Specifically,
      significantly increased risks were observed for thyroid cancer (O/E, 2.32; 95%
      CI, 1.16-4.16), pancreatic cancer (O/E, 2.38; 95% CI, 1.43-3.72), non-bladder
      urothelial malignancies (O/E, 4.27; 95% CI, 1.57-9.29), bladder cancer (O/E,
      1.47; 95% CI, 1.01-2.28), all haematological malignancies (O/E, 1.44; 95% CI,
      1.08-1.89) and non-Hodgkin's lymphoma (O/E, 1.77; 95% CI, 1.22-2.48). * Patients
      had a persistently elevated risk of SPMs 15 years from the time of initial
      clinical stage I testicular seminoma diagnosis (O/E, 1.29; 95% CI, 1.10-1.49).
      CONCLUSIONS: * We confirmed the increased risk of SPMs after EBRT for seminoma,
      and we identified the specific types of SPMs that develop. * The risk of EBRT
      associated SPM persists for years after the initial seminoma diagnosis, and
      patients should be informed about these long-term risks.

PMID- 21883829
TI  - Elective partial nephrectomy is equivalent to radical nephrectomy in patients
      with clinical T1 renal cell carcinoma: results of a retrospective, comparative,
      multi-institutional study.
AB  - OBJECTIVE: To compare the oncological outcomes of patients who underwent elective
      partial nephrectomy (PN) or radical nephrectomy (RN) for clinically organ
      confined renal masses <=7 cm in size (cT1). PATIENTS AND METHODS: The records of
      3480 patients with cT1N0M0 disease were extracted from a multi-institutional
      database and analyzed retrospectively. RESULTS: In patients who underwent PN, the
      risk of clinical understaging was 3.2% in cT1a cases and 10.6% in cT1b cases.
      With regard to the cT1a patients, the 5- and 10-year cancer-specific survival
      (CSS) estimates were 94.7% and 90.4%, respectively, after RN and 96.1% and 94.9%,
      respectively, after PN (log-rank test: P = 0.01). With regard to cT1b patients,
      the 5-year CSS probabilities were 92.6% after RN and 90% after PN, respectively
      (log-rank test: P = 0.89). Surgical treatment failed to be an independent
      predictor of CSS on multivariable analysis, both for cT1a and cT1b patients.
      Interestingly, PN was oncologically equivalent to RN also in patients with pT3a
      tumours (log-rank test: P = 0.91). CONCLUSIONS: Elective PN is not associated
      with an increased risk of recurrence and cancer-specific mortality in both cT1a
      and cT1b tumours. Data from the present study strongly support the use of partial
      nephrectomy in patients with clinically T1 tumours, according to the current
      recommendations of the international guidelines.

PMID- 21883830
TI  - Cost-effectiveness analysis of degarelix for advanced hormone-dependent prostate
      cancer.
AB  - OBJECTIVE: To evaluate the cost-effectiveness of degarelix vs luteinizing hormone
      releasing hormone analogue (triptorelin) plus short-term antiandrogen treatment
      for advanced prostate cancer. METHODS: We developed a decision analytic model
      based on a clinical trial and literature review. The two interventions evaluated
      were: (i) monthly injection of degarelix and (ii) 3-monthly triptorelin therapy
      plus short-term flutamide, cyproterone or bicalutamide treatment. The model
      consisted of a decision tree monitoring a hypothetical cohort of patients aged 70
      years from the start of hormonal treatment to the end of the first month, and a
      Markov model monitoring patients from the end of month 1 for a time horizon of 10
      years (i.e. when 96% of patients are assumed to have died). The base-case
      analysis assumed patients present with asymptomatic metastatic prostate cancer.
      Costs and outcomes were collected over the model time horizon. Outcome measures
      were quality-adjusted life years (QALYs), lifetime costs and incremental cost
      effectiveness ratios. Sensitivity analyses (one-way and multi-way) and
      probabilistic sensitivity analyses were conducted to explore the uncertainties
      around the assumptions. RESULTS: In the base-case analysis, the incremental cost
      effectiveness ratio (ICER) for degarelix vs triptorelin plus antiandrogen was
      L59,000 per QALY gained. The model was most sensitive to the rate of significant
      adverse events in the triptorelin plus antiandrogen group. The model was also
      sensitive to the assumed survival of patients with metastatic prostate cancer and
      the price of degarelix. The results of the probabilistic sensitivity analyses
      suggested that there was a low probability (9.6%) of degarelix being the most
      cost-effective treatment option when a willingness-to-pay threshold of L30,000
      per QALY gained is assumed. CONCLUSION: Degarelix is unlikely to be cost
      effective compared to triptorelin plus short-term antiandrogen in the management
      of advanced prostate cancer with respect to the usual thresholds of cost
      effectiveness used in the UK: L20,000-30,000 per QALY gained (used by the
      National Institute for Health and Clinical Excellence).

PMID- 21883831
TI  - Role of Rho-kinase and protein kinase C during contraction of hypertrophic
      detrusor in mice with partial urinary bladder outlet obstruction.
AB  - OBJECTIVE: To study muscarinic/purinergic receptor activation and Rho
      kinase/protein kinase C (PKC) signalling during smooth muscle contraction in
      normal and hypertrophic mouse urinary bladders. METHODS: Partial urinary outflow
      obstruction was induced in adult female (10-12 weeks) C57Bl/6 mice and
      comparisons were made with sham-operated controls. Bladder preparations were
      examined in vitro. Expression of signalling proteins was examined using Western
      blot analysis. RESULTS: Obstructed bladders increased more than threefold in
      weight and were found to have enhanced muscarinic and attenuated purinergic
      components during nerve-induced contractions. The contractile response to
      carbachol was shifted towards lower concentrations of carbachol for the peak
      response and had a markedly enhanced sustained component. The amplitude of the
      alpha,beta-methylene ATP-induced responses was lowered. Rho-kinase inhibitor
      Y27632 (10 uM) inhibited peak and sustained contractile responses to carbachol in
      control bladders (peak by 38%; plateau 57%) and obstructed bladders (peak 37%
      plateau 47%). PKC inhibitor GF109203X (1 uM) inhibited carbachol contractions in
      controls (peak by 29%; plateau 29%) and obstructed bladders (peak 17%; plateau
      12%). Inhibition by a similar extent was observed after nerve stimulation.
      Sensitivity to Ca(2+) in high-K(+) depolarized intact tissues increased in
      obstructed bladders. This increased receptor-independent Ca(2+)-sensitivity was
      abolished by Y27632. Tissue contents of the myosin-binding phosphatase subunit
      MYPT-1 and catalytic phosphatase subunit PP1beta, were decreased and the contents
      of RhoGDI, RhoA and CPI-17 increased. A decrease in the Rho-kinase isoform ROCK-1
      was observed. CONCLUSION: Based on these results, one can speculate that Rho
      kinase inhibition would preferentially target the pathological phasic activity in
      the urinary bladder rather than inhibit the physiological receptor-mediated
      bladder emptying.

PMID- 21883832
TI  - Prevalence of hesitancy in 30-80-year-old Finnish men: Tampere Ageing Male
      Urological Study (TAMUS).
AB  - Study Type--Therapy (symptom prevalence). Level of Evidence 2a. What's known on
      the subject? and What does the study add? In several population-based studies the
      prevalence of hesitancy has varied from 20% to 52%. Studies concern mostly older
      men >=50-years-old. Knowledge of troublesomeness that hesitancy causes is very
      scarce. This is a large population-based study on hesitancy in men with a wide
      age range. This study reports the prevalence of hesitancy from 30-year-old men to
      80-year-old men. The bother of hesitancy is reported and this is also presented
      in different age groups. OBJECTIVE: * To estimate the prevalence and bother of
      hesitancy by age group. MATERIALS AND METHODS: * In this population-based study,
      the target population was 30- to 80-year-old men from Pirkanmaa County, Finland.
      * Information was collected by means of a mailed self-administered questionnaire
      in 2004. The overall participation proportion was 58.7% (4384 men out of 7470). *
      The Danish Prostatic Symptom Score (DAN-PSS-1) questionnaire was used to evaluate
      urinary symptoms, particularly hesitancy. Logistic regression was used for
      multivariate analysis. RESULTS: * Almost half of the men (46.8%, 95% CI 45.3
      48.3%) reported hesitancy at least occasionally, but only 0.5% (95% CI 0.3-0.7%)
      had hesitancy every time they urinated. The prevalence of any hesitancy was 42.3%
      at 30 years and 50.5% at 80 years of age (trend P < 0.001). Only a few men
      reported hesitancy often or always, prevalence increasing with age from 2.6% to
      11.4% (trend P < 0.001). * Hesitancy caused a small problem for 18.3% of the men
      and a moderate or major problem for 0.9-5.3%. Only 3% of the men with infrequent
      hesitancy reported more than a small problem, whereas 59% of the men with
      hesitancy often or always reported a small problem and 32% reported a moderate or
      major problem. * Two other voiding symptoms, straining and weak stream, were
      strongly associated with hesitancy (with odds ratios exceeding 80). CONCLUSIONS:
      * Mild hesitancy is very common in men of all ages. * Severe cases are rare, but
      the prevalence increases with age. * Hesitancy is a well-tolerated urinary
      symptom.

PMID- 21883833
TI  - Sentinel node detection in renal cell carcinoma. A feasibility study for
      detection of tumour-draining lymph nodes.
AB  - OBJECTIVE: To evaluate the feasibility of performing sentinel node detection in
      patients with renal cell carcinoma (RCC). MATERIALS AND METHODS: An open series
      of 13 arbitrarily selected patients with T1b-T3b RCC scheduled for radical
      nephrectomy at a single Tertiary Academic Centre were examined with different
      modalities of sentinel node detection. Preoperative ultrasonography-guided
      injection of radioactive isotope, lymphoscintigram and single photon emission
      computed tomography/computed tomography, followed by intraoperative gamma-probe
      detection and Patent Blue detection, as well as postoperative scintigram of the
      main specimen were the planned interventions. These investigations were performed
      in conjunction with intended open radical nephrectomy. RESULTS: In 10 of the 13
      patients sentinel node detection was achieved with 32 sentinel nodes displayed.
      Radio-guided surgery using an intraoperative gamma-probe resulted in the highest
      realtive detection rate with detection of sentinel nodes in nine patients. In
      total, nine metastatic sentinel nodes were detected in three patients. One
      patient, preoperatively staged as N+, was restaged after sentinel node detection
      and histopathology as pN0. CONCLUSIONS: Sentinel node detection in renal tumours
      is feasible although evaluation of different modes of detection needs further
      refinement and standardization. All nodes preoperatively detected by routine
      computed tomography as suspicious metastatic lesions were confirmed as sentinel
      nodes, including two nodes considered as metastatic by preoperative routine
      imaging but ultimately staged as non-metastatic sentinel nodes.

PMID- 21883834
TI  - Assessment of lower urinary tract symptoms in men by international prostate
      symptom score and core lower urinary tract symptom score.
AB  - Study Type - Therapy (symptom prevalence). Level of Evidence 2a. What's known on
      the subject? and What does the study add? The International Prostate Symptom
      Score (IPSS) has been most commonly used for the symptom assessment of men with
      lower urinary tract symptoms (LUTS). However, LUTS in men are so variable that
      they may not be fully captured by the IPSS questionnaire alone. This study has
      demonstrated that the Core Lower Urinary Tract Symptom Score (CLSS)
      questionnaire, which addresses 10 important symptoms, is an appropriate initial
      assessment tool for LUTS in men with various diseases/conditions. OBJECTIVE:
      International Prostate Symptom Score (IPSS) has been commonly used to assess
      lower urinary tract symptoms (LUTS). We have recently developed Core Lower
      Urinary Tract Symptom Score (CLSS). The aim of this study is to compare IPSS and
      CLSS for assessing LUTS in men. PATIENTS AND METHODS:  Consecutive 515 men
      fulfilled IPSS and CLSS questionnaires. IPSS QOL Index was used as the QOL
      surrogate. The clinical diagnoses were BPH (n = 116), BPH with OAB wet (n =80),
      prostate cancer (n = 128), prostatitis (n = 68), underactive bladder (n = 8),
      others (n = 72), and controls (e.g., occult blood) (n = 42). Simple statistics
      and predictability of poor QOL (QOL Index 4 or greater) were examined. RESULTS:
      All symptom scores were significantly increased in symptomatic men compared with
      controls. Scores of corresponding symptoms of two questionnaires were
      significantly correlated (r = 0.58-0.85, all P < 0.0001). A multivariate
      regression model to predict poor QOL indicated nine symptoms (daytime frequency,
      nocturia, urgency, urgency incontinence, slow stream, straining, incomplete
      emptying, bladder pain and urethral pain) as independent factors. The hazard
      ratios for bladder pain (2.2) and urgency incontinence (2.0) were among the
      highest. All the nine symptoms are addressed in CLSS, while three symptoms
      (urgency incontinence, bladder, and urethral pain) are dismissed in IPSS.
      CONCLUSION: CLSS questionnaire is more comprehensive than IPSS questionnaire for
      symptom assessment of men with various diseases/conditions, although both
      questionnaires can capture LUTS with possible negative impact on QOL.

PMID- 21883835
TI  - Diffusion-weighted magnetic resonance imaging in patients selected for radical
      cystectomy: detection rate of pelvic lymph node metastases.
AB  - OBJECTIVE: To evaluate whether DW-MRI improves the detection of pelvic lymph
      nodes metastates in patients with bladder cancer undergoing radical cystectomy.
      PATIENTS AND METHODS: 36 patients with CT scan negative for nodal metastates
      underwent DW-MRI before surgery. Diagnostic accuracy of DW-MRI was compared with
      histopathological findings. RESULTS: Mean ADC value was 0.85 * 10(-3) mm(3)/s in
      the nodal metastatic group and 1 * 10(-3) mm(3)/s in the nodal non-metastatic
      group (P = 0.02). The ADC cut-off value, obtained by the ROC curve was 0.86 * 10(
      3) mm(3)/s. Patient-based sensitivity, specificity and positive and negative
      predictive values were 76.4%, 89.4%, 26.6%, and 71.4%, respectively. CONCLUSION:
      DW-MRI may be used to differentiate metastatic from non-metastatic lymph nodes in
      patients with high-grade bladder cancer.

PMID- 21883836
TI  - Hormone therapy for prostate cancer and the risk of stroke: a 5-year follow-up
      study.
AB  - OBJECTIVE: To examine the 5-year risk of stroke among patients with prostate
      cancer (PC) receiving androgen deprivation therapy (ADT) in Taiwan, using a
      population-based dataset. PATIENTS AND METHODS: This prospective case-control
      study used data sourced from the Longitudinal Health Insurance Database. The
      study included 365 patients with PC; 64 (17.6%) received ADT for more than 1
      month. Cox proportional hazards regression was used to evaluate the association
      between ADT and the risk of stroke during the subsequent 5-year follow-up period,
      after adjusting for sociodemographic characteristics and hypertension, diabetes,
      coronary heart disease, heart failure, atrial fibrillation and hyperlipidaemia.
      RESULTS: In the total sample of 365 patients with PC, 68 (18.6%) patients had
      strokes during the 5-year follow-up period. These included 11 patients with PC
      who received ADT (17.2% of all patients who received ADT) and 57 patients who did
      not receive ADT (18.9% of patients who did not receive ADT). After adjusting for
      potential confounders, no significant difference in the hazard of stroke was
      found between patients with PC who did and did not receive ADT (hazard ratio,
      1.09; 95% confidence interval, 0.80-1.50). CONCLUSION: There was no significant
      difference in the risk of stroke between ethnic Chinese patients with PC who did
      and did not receive ADT, after adjusting for potential confounders.

PMID- 21883837
TI  - Upper urinary tract transitional cell carcinoma: location is not correlated with
      prognosis.
AB  - OBJECTIVE: To identify the impact of tumour location on the disease recurrence
      and survival of patients who were treated surgically for upper urinary tract
      transitional cell carcinoma (UUT-TCC). PATIENTS AND METHODS: A single-centre
      series of 189 consecutive patients who were treated surgically for UUT-TCC
      between January 1999 and December 2009 was evaluated. Patients who had previously
      undergone radical cystectomy, preoperative chemotherapy or contralateral UUT-TCC
      were excluded. In all, 133 patients were available for evaluation. Tumour
      location was categorized as renal pelvis or ureter based on the location of the
      dominant tumour. Recurrence-free probabilities and cancer-specific survival were
      estimated using the Kaplan-Meier method and Cox regression analyses. RESULTS: The
      5-year recurrence-free and cancer-specific survival estimates for the cohort in
      the present study were 66% and 62%, respectively. The 5-year bladder-only
      recurrence-free probability was 76%. Using multivariate analysis, only pT
      classification (hazard ratio, HR, 2.46; P = 0.04) and demographic characteristics
      (HR, 2.86 for areas of Balkan endemic nephropathy, vs non-Balkan endemic
      nephropathy areas; 95% confidence interval, 1.37-5.98; P = 0.005) were associated
      with disease recurrence. Tumour location was not associated with disease
      recurrence in any of the analyses. There was no difference in cancer-specific
      survival between renal pelvis and ureteral tumours (P = 0.476). Using
      multivariate analysis, pT classification (HR, 8.04; P = 0.001) and lymph node
      status (HR, 4.73; P = 0.01) were the only independent predictors associated with
      a worse cancer-specific survival. CONCLUSION: Tumour location is unable to
      predict outcomes in a single-centre series of consecutive patients who were
      treated with radical nephroureterectomy for UUT-TCC.

PMID- 21883838
TI  - Prognostic factors and outcome in patients with T1 high-grade bladder cancer: can
      we identify patients for early cystectomy?
AB  - OBJECTIVE: To assess outcome in patients with T1 high-grade (T1HG) bladder cancer
      treated at a single academic institution and to determine the prognostic factors
      that can help in counselling patients towards early cystectomy. PATIENTS AND
      METHODS: Records of 2570 patients with bladder cancer treated from 1995 to 2005
      were reviewed. Only patients diagnosed with T1HG disease were included in the
      analysis. Collected variables included various clinicopathological parameters,
      use of statins, smoking, as well as dates of recurrence, progression, radical
      cystectomy and death. Recurrence-free survival (RFS) and worsening-free survival
      (WFS) were analyzed. Multivariate Cox proportional regression analysis was
      employed to verify the prognostic significance of various variables. RESULTS: In
      total, 278 (10.8%) patients were identified as having T1HG disease on
      transurethral resection. 66% of patients who recurred, and 36.3% developed stage
      progression after a median (range) follow-up of 3 (0.1-15.4) years. 30% patients
      who underwent radical cystectomy, and 9% were dead of disease. The 5-year RFS and
      WFS rates were 26.6% and 49.4%, respectively. On multivariate analysis, only non
      trigonal tumour location, restaging transurethral resection, history of previous
      carcinoma not invading bladder muscle and adjuvant bacille Calmette-Guerin (BCG)
      therapy were significantly associated with prolonged RFS, whereas papillary
      tumour architecture, history of previous carcinoma not invading bladder muscle
      and adjuvant BCG therapy were significantly associated with prolonged WFS.
      CONCLUSIONS: Patients with T1HG bladder cancer are at a significant risk of
      progression and death from disease. Primary tumours, sessile architecture and
      trigonal location are factors associated with a worse outcome and may be used to
      counsel patients towards early cystectomy.

PMID- 21883839
TI  - Tubeless vs standard percutaneous nephrolithotomy: a meta-analysis.
AB  - OBJECTIVE: To systematically review and compare tubeless percutaneous
      nephrolithotomy (PCNL) with standard PCNL. MATERIALS AND METHODS: We conducted a
      review of the English language literature on studies involving randomized
      controlled trials for PCNL. The studies chosen to be included in our review
      compared tubeless PCNL with standard PCNL and described the advantages of each in
      the outcomes. Two reviewers independently screened the studies for eligibility,
      evaluated their quality and extracted the data from the eligible studies, with
      confirmation by cross-checking. Data were processed using RevMan 5.0. RESULTS:
      Seven studies involving 1365 cases met the inclusion criteria, and these were
      included in the meta-analysis. The patients' baseline characteristics were
      comparable in all the studies. By comparing the four common characteristics, we
      found no difference in efficacy between the two surgical approaches in terms of
      mean operation duration and postoperative haematocrit change (P > 0.05). We found
      that the mean analgesic requirement and number of days in hospital were lower for
      tubeless PCNL (P < 0.05). CONCLUSIONS: Our results show that tubeless PCNL is a
      good option in non-complicated cases, with the advantages of reduced hospital
      stay and little need for postoperative analgesia. There was no difference between
      the two approaches in operation duration, or haematocrit change after surgery. As
      only few studies with small study populations were available, more high quality
      larger trials with longer follow-up are recommended.

PMID- 21883840
TI  - Chemotherapy for advanced adrenal cancer: improvement from a molecular approach?
AB  - Advanced adrenal carcinoma remains a significant therapeutic challenge, with
      conventional approaches to systemic therapy having failed to achieve sustained
      objective remissions or major survival benefit in most instances. Several
      systemic therapies, including mitotane, suramin and gossypol, as well as
      cytotoxic agents, such as cisplatin and etoposide, have produced responses of ~15
      30%, with median survival figures of ~6-15 months, depending on case selection
      bias, with only <10% 5-year survival rates. Recent preclinical and pathological
      studies have indicated a range of potential targets for drugs, including WNT/beta
      catenin, epidermal growth factor receptor, RAF and k-RAS; similar applications in
      melanoma and renal carcinoma have achieved significant gains, and these targets
      are worthy of further, structured investigation. Advanced adrenal carcinoma
      constitutes an orphan disease, with a high mortality rate, and merits investment
      in clinical trials.

PMID- 21883841
TI  - Assessment of lower urinary tract symptoms in men by international prostate
      symptom score and core lower urinary tract symptom score.

PMID- 21883842
TI  - Association of prolactin-induced protein with preputial development of
      hypospadias.
AB  - OBJECTIVE: To investigate the molecular aetiology of hypospadias during a
      critical developmental period by identifying differentially regulated genes in
      the tissues of individuals with hypospadias and comparing these genes with
      similar genes in the tissues of control individuals. MATERIALS AND METHODS:
      Pregnant Sprague-Dawley rats were administered flutamide (7.5 mg) on gestational
      days 15-17 to produce hypospadiac pups. Dams were killed on gestational day 17,
      and the genital tubercles (GTs) of male pups were harvested. Gene expression of
      RNA isolated from the GTs was analysed using an oligonucleotide microarray
      containing 20,500 genes. The results of microarray analysis were confirmed using
      quantitative real-time PCR (qPCR). Protein expression levels were studied using
      Western blot analysis. The distribution of genes associated with GT development
      in rats was histologically examined. Prepuces harvested from patients with
      hypospadias and phimosis were immunohistochemically examined for gene
      distribution. RESULTS: Of the 20, 500 genes, 23 annotated genes, including
      prolactin-induced protein (Pip), in the GTs of the hypospadiac rats were
      expressed at levels less than half of that of similar genes in the GTs of the
      control rats. Findings from qPCR and Western blot analysis revealed significantly
      lower Pip/PIP expression in the GTs of the hypospadiac rats than in those of the
      control rats. Immunohistochemical analysis revealed PIP expression in the
      prepuces of the GTs of the control and hypospadiac rats. PIP was expressed in the
      human prepuces of the patients with hypospadias and phimosis. CONCLUSIONS:
      Pip/PIP, expressed at low levels in the GTs of hypospadiac rats, may be
      associated with preputial development. This model can be useful to elucidate the
      molecular mechanisms underlying penile and urethral development as well as
      preputial development. Further studies should provide detailed information
      regarding the molecular aetiology of hypospadias.

PMID- 21883843
TI  - Is joint hypermobility associated with vesico-ureteral reflux? An assessment of
      50 patients.
AB  - OBJECTIVE: To assess whether there is an increased prevalence of joint
      hypermobility in patients with vesico-ureteric reflux (VUR). MATERIALS AND
      METHODS: We studied 50 patients with primary VUR and matched controls drawn from
      a reference population. Joint mobility was assessed using the Bulbena
      hypermobility score. RESULTS: We identified significantly more patients with VUR
      with generalized joint hypermobility than controls (24% vs 6.7%, P= 0.007).
      CONCLUSION: Our findings confirm our clinical observation of an increased rate of
      joint hypermobility in patients with VUR. We speculate that an altered
      composition of the connective tissue may contribute to the severity of the (pre
      existing) VUR phenotype.

PMID- 21883844
TI  - Prospective multi-centre study of adjustable single-incision mini-sling
      (Ajust((r)) ) in the management of stress urinary incontinence in women: 1-year
      follow-up study.
AB  - OBJECTIVES: To determine whether an adjustable single-incision mini-sling (SIMS,
      Ajust((r)) ) is safe and effective in the management of female stress urinary
      incontinence (SUI) at 12 months follow-up. To determine whether it is feasible to
      be performed under local anesthesia (LA). MATERIALS AND METHODS: The present
      study is a multicentre prospective cohort study in which 90 female patients
      underwent SIMS-Ajust((r)) using a standardized insertion technique. The last 45
      women were offered the procedure under LA. All patients completed their 12-month
      follow-up. RESULTS: The patient-reported success rate, using Patient Global
      Impression of Improvement (PGI-I), was 80% at 12 months follow-up and a further
      6% (n= 5) reported themselves to be 'improved'. In all, 32/45 (71%) patients
      agreed to undergo the procedure under LA while one patient required conversion to
      general anaesthetic. There was no organ damage or requirement for blood
      transfusion. Significantly lower rates of blood loss (P= 0.025) and postoperative
      voiding difficulties (P= 0.026) were seen in the LA group. The re-operation rate
      for SUI was 6% at 12 months. CONCLUSIONS: SIMS (Ajust) appears to be a safe
      procedure, which is feasible under LA. SIMS (Ajust) have an 80% patient-reported
      success rate at 12 months follow-up.

PMID- 21883845
TI  - Information needs of men on androgen deprivation therapy.
AB  - Study Type - Needs assessment survey Level of Evidence 2b. What's known on the
      subject? and What does the study add? Although androgen deprivation therapy (ADT)
      is widely used to treat men with prostate cancer, little is known about the
      information needs of patients on ADT. We found that patients are generally very
      satisfied with using ADT and expressed minimal decisional regret with its use up
      to four years later. For men receiving ADT in the adjuvant setting, their
      survival estimates with the addition of ADT were quite reasonable when compared
      to findings in randomized trails. A key area to enhance patient education appears
      to be side effects, especially around hot flashes and fatigue, which were also
      the most bothersome treatment sequelae for patients. OBJECTIVE: To evaluate
      information needs of men receiving androgen deprivation therapy (ADT). PATIENTS
      AND METHODS:   A cross-sectional survey was distributed to English-speaking
      prostate cancer patients receiving ADT adjuvant to radical therapy or for
      biochemical relapse. Three cohorts were recruited based on duration of ADT use:
      <6 months (cohort 1), 6-18 months (cohort 2) and 18 months to 4 years (cohort 3).
      Several validated questionnaires were used, including the Control Preferences
      Scale (CPS), Satisfaction with Treatment Decision Scale (SWD) and Decisional
      Regret Scale (DRS). Patients on adjuvant ADT were asked to estimate their overall
      survival with and without ADT. RESULTS: Eighty-five men were recruited, of whom
      91.8% were receiving a gonadotrophin-releasing hormone agonist, 4.7% were
      receiving anti-androgen monotherapy and 3.5% were receiving combined androgen
      blockade. Patients preferred the following decision-making roles: 23.5% active,
      50.6% collaborative, 27.0% passive. Mean patient satisfaction for ADT use was
      high at 24.0/30 and decisional regret was low at 7.9/25. There was a perceived
      overall survival benefit of 3.9-6.9% at 5 years, 3.6-17.8% at 10 years and 5.7
      18.1% at 15 years with the addition of adjuvant ADT.   Hot flushes and fatigue
      were reported as the most common theoretical adverse effects as well as those
      experienced most commonly by patients. CONCLUSIONS:   Patients on ADT were
      generally satisfied with their decisions to start ADT and expressed minimal
      decisional regret up to 4 years later. A key area to enhance patient education
      appears to be adverse effects, especially around hot flushes and fatigue.

PMID- 21883846
TI  - Partial nephrectomy in two patients with known T3a tumours involving the renal
      vein.
AB  - Study Type--Therapy (case series). Level of Evidence 4. What's known on the
      subject? And what does the study add? Although nephron-sparing surgery (NSS) has
      became accepted therapy for T1 tumours, radical nephrectony is considered the
      best therapy for T3a tumours involving the renal vein. NSS can be considered in
      T3a or greater tumours if imperative indications exist, such as bilateral disease
      or solitary kidney. However, there is little published data on the
      characteristics of these patients, the impact of surgery on their renal function,
      and long-term oncologic outcomes. This study profiles single-institution
      experience with nephron-sparing surgery for known T3a tumours involving the renal
      vein, including patient characteristics, tumour characteristics, preoperative and
      follow-up imaging, preoperative and follow-up estimated glomerular filtration
      rate, length of temporary postoperative haemodialysis, and oncologic outcome.
      Additionally, we compare this to other published data on nephron-sparing surgery
      for similar tumors. OBJECTIVE: * To present two patients with T3a tumours
      involving the renal vein who underwent nephron-sparing surgery (NSS) for
      imperative reasons. PATIENTS AND METHODS: * Retrospective chart review of
      patients who underwent NSS for renal cell carcinoma (RCC) with known renal vein
      tumour thrombus (RVTT). * Both patients underwent open partial nephrectomy and
      renal vein thrombectomy of a solitary kidney. * Primary outcomes of the study
      include radiographic evidence of recurrence, haemodialysis requirement and
      estimated glomerular filtration rate (eGFR) before and after surgery. RESULTS: *
      Patient 1 is 24 months from NSS and has no evidence of recurrence based on CT
      scan. His final pathology revealed a 9-cm, T3a, clear cell, Fuhrman grade II
      carcinoma. He spent 42 days on haemodialysis and is now off all dialysis. His
      preoperative and most recent eGFR are 48 and 23 mL/min/1.73 m(2) based on the
      Modification of Diet in Renal Disease (MDRD) equation and 69.4 and 29.8 mL/min by
      the Cockcroft-Gault equation. * Patient 2 is 9 months from NSS and has no
      evidence of recurrence based on CT scan. Her final pathology revealed a 6-cm,
      T3a, clear cell, Fuhrman grade II-III carcinoma. She spent 30 days on
      haemodialysis and is now off all dialysis. Her preoperative and most recent eGFR
      are 58 and 30 mL/min/1.73 m(2) based on the MDRD equation and 62.2 and 32.8
      mL/min by the Cockcroft-Gault equation. CONCLUSION: * Based on our review,
      preservation of renal function and favourable oncological outcome can be
      accomplished with NSS in patients with known stage T3a RCC with RVTT and should
      be considered in carefully selected patients.

PMID- 21883847
TI  - Prognostic role of ECOG performance status in patients with urothelial carcinoma
      of the upper urinary tract: an international study.
AB  - OBJECTIVE: To evaluate the prognostic role of ECOG Performance status (ECOG-PS)
      in a large multi-institutional international cohort of patients treated with
      radical nephroureterectomy for upper tract urothelial carcinoma. MATERIALS AND
      METHODS: Data of 427 patients treated with radical nephroureterectomy at five
      international institutions in Asia, Europe and Northern America were collected
      retrospectively from 1987 to 2008. Logistic and Cox regression models were used
      for univariable and multivariable analyses. RESULTS: ECOG-PS was 0 in 272 of 427
      (64%) patients. The median follow-up of the whole cohort was 32 months. The five
      year recurrence-free (RFS), cancer-specific (CSS) and overall (OS) survival
      estimates were 71.7%, 74.9% and 68.5%, respectively, in patients with ECOG-PS 0
      compared with 60.1%, 67.8%, and 51.4% respectively, in patients with ECOG-PS >=1
      (P value 0.08 for RFS, 0.43 for CSS, and <0.001 for OS, respectively). On
      multivariable Cox regression analyses, ECOG-PS was not an independent predictor
      of either RFS (hazard ratio 1.4; P = 0.107) or CSS (hazard ratio 1.2; P = 0.426)
      but was an independent predictor of OS (hazard ratio 1.5; P = 0.03). CONCLUSIONS:
      In this large multicentre international study, ECOG-PS was not significantly
      associated with RFS and CSS. Conversely we find a strong association with
      survival 1-month after surgery and OS. Further research is needed to ascertain
      the additive prognostic role of ECOG-PS in well-designed prospective multicentre
      studies.

PMID- 21883848
TI  - Symptom profile variability of interstitial cystitis/painful bladder syndrome by
      age.
AB  - Study Type--Diagnostic (symptom prevalence). Level of Evidence 2b. What's known
      on the subject? And what does the study add? Symptom variability is profound in
      the population of patients diagnosed with interstitial cystitis and painful
      bladder syndrome because these diagnoses represent a very heterogeneous patient
      population. Recently, younger patients are being diagnosed with these pain
      syndromes, without any specific investigation into the symptoms they experience.
      We identified that patients diagnosed with interstitial cystitis and painful
      bladder syndrome have variable clinical symptom profiles depending on the age at
      the time of their diagnosis. Dyspareunia, external genitalia pain, urgency,
      frequency and dysuria were more common in younger patients whereas nocturia,
      urinary incontinence and the presence of Hunner's ulcers were more common in
      older patients. Better defining symptom profiles for patients at the time of
      evaluation may potentially aid in more accurate and expedited diagnosis of these
      conditions, particularly in the youngest patient population which is being
      recognized more commonly in recent times. OBJECTIVE: * To investigate the
      clinical profile differences among patients with interstitial cystitis/painful
      bladder syndrome (IC/PBS) based upon age at the time of diagnosis from childhood
      into the geriatric age group. METHODS: * An analysis of 268 patients with IC/PBS
      seen between 1990 and 2008 was performed. * Three age cohorts were analysed: <30
      years, >=30 years but <60 years, and >=60 years of age at time of diagnosis. *
      Patient demographics, disease characteristics and IC/PBS-associated symptoms were
      compared across the three groups. RESULTS: * Of the 268 patients, 60 were <30
      years of age at the time of IC diagnosis (median 22, range 11-29), 105 were >=30
      but <60 years (median 48, range 30-59) and 103 patients were >=60 years of age
      (median 69, range 60-88). * Of the patients in the youngest, middle and oldest
      age cohorts: 12.0, 42.0 and 39.8% had Hunner's ulcers, respectively (P<0.001). *
      Dyspareunia and external genitalia pain were more common in the youngest age
      cohort, P<0.001 and P=0.001, respectively. * Urinary urgency (P=0.033), frequency
      (P=0.006) and dysuria (P<0.001) were also more common in patients diagnosed
      before 30 years of age. * The reported rate of nocturia and urinary incontinence
      increased with age, P=0.002 and P<0.001, respectively. CONCLUSIONS: * Patients
      with IC/PBS analysed across a wide spectrum of ages at time of diagnosis
      portrayed a unique symptom profile pattern. * Patients diagnosed at the youngest
      ages experienced significantly more urinary urgency, frequency, dysuria,
      dyspareunia and pain in their external genitalia. * Older patients had higher
      rates of nocturia, urinary incontinence and Hunner's ulcer disease.

PMID- 21883849
TI  - Stage-specific impact of pelvic lymph node dissection on survival in patients
      with non-metastatic bladder cancer treated with radical cystectomy.
AB  - OBJECTIVE: To examine the effect of stage-specific pelvic lymph node dissection
      (PLND) on cancer-specific (CSM) and overall mortality (OM) rates at radical
      cystectomy (RC) for bladder cancer. METHODS: Overall, 11,183 patients were
      treated with RC within the Surveillance, Epidemiology, and End Results database.
      Univariable and multivariable Cox regression analyses tested the effect of PLND
      on CSM and OM rates, after stratifying according to pathological tumour stage.
      RESULTS: Overall, PLND was omitted in 25% of patients, and in 50, 35, 27, 16 and
      23% of patients with respectively pTa/is, pT1, pT2, pT3 and pT4 disease (P <
      0.001). For the same stages, the 10-year CSM-free rates for patients undergoing
      PLND compared with those with no PLND were, respectively, 80 vs 71.9% (P = 0.02),
      81.7 vs 70.0% (P < 0.001), 71.5 vs 56.1% (P = 0.001), 43.7 vs 38.8% (P = 0.006),
      and 35.1 vs 32.0% (P = 0.1). In multivariable analyses, PLND omission was
      associated with a higher CSM in patients with pTa/is, pT1 and pT2 disease (all P
      <= 0.01), but failed to achieve independent predictor status in patients with pT3
      and pT4 disease (both P >= 0.05). Omitting PLND predisposed to a higher OM across
      all tumour stages (all P <= 0.03). CONCLUSIONS: Our results indicate that PLND
      was more frequently omitted in patients with organ-confined disease. The
      beneficial effect of PLND on cancer control outcomes was more evident in these
      patients than in those with pT3 or pT4 disease. PLND at RC should always be
      considered, regardless of tumour stage.

PMID- 21883850
TI  - Subcapsular renal haematoma after holmium:yttrium-aluminum-garnet laser
      ureterolithotripsy.
AB  - OBJECTIVE: To report the incidence, risk factors, and outcomes of subcapsular
      renal haematoma (SRH) after ureteroscopic lithotripsy (URSL) using
      holmium:yttrium-aluminum-garnet (Ho:YAG) laser to treat ureteric stones. PATIENTS
      AND METHODS: Prospective data from 2848 URSLs performed between January 2003 and
      September 2010 were retrospectively analysed. In all 11 patients were identified
      as having a SRH after URSL if they had persistent severe ipsilateral flank pain
      or a palpable mass within a day of surgery, or presented with radiographic
      evidence of a SRH. Risk factors for the development and course of the SRH were
      reported. RESULTS: Of the 2848 consecutive patients treated with URSL using
      Ho:YAG laser, 11 (0.4%) developed a SRH after surgery. Patients who developed a
      SRH had larger stones (1.4 vs 0.9 cm, P < 0.001), more severe ipsilateral
      hydronephrosis (P < 0.001), longer operation duration (41 vs 33 min, P < 0.001),
      and higher perfusion pressure of hydraulic irrigation (176.8 vs 170.2 mmHg, P <
      0.001) than patients who did not develop a SRH. Patient age, sex, body mass
      index, presence of diabetes mellitus, history of urolithiasis and hypertension,
      presence of multiple stones, stone location and flow rate of hydraulic irrigation
      were not statistically different in patients who did or did not develop a SRH.
      Most patients were managed conservatively, with no further intervention or with a
      flank drain, until the SRH resolved. Overall, in three patients the SRH resolved
      with no further intervention, six patients were treated with a drain only, and
      two patients had open surgery within a day of presenting with SRH. CONCLUSIONS:
      The rate of development of SRH after URSL is very low. Most patients who present
      with a SRH after URSL, can be treated conservatively with no intervention or with
      a drain only.

PMID- 21883851
TI  - Trends in urological stone disease.
AB  - OBJECTIVE: To summarize the changes in prevalence and treatment of upper urinary
      tract stone disease in the UK over the last 10 years. METHODS: Data from the
      Hospital Episode Statistics (HES) website (http://www.hesonline.nhs.uk) were
      extracted, summarized and presented. RESULTS: The number of upper urinary tract
      stone hospital episodes increased by 63% to 83,050 in the 10-year period. The use
      of shock wave lithotripsy (SWL) for treating all upper tract stones increased
      from 14,491 cases in 2000-2001 to 22,402 cases in 2010 (a 55% increase) with a
      69% increase in lithotripsy for renal stones. There was a 127% increase in the
      number of ureteroscopic stone treatments from 6,283 to 14,242 cases over the 10
      year period with a 49% increase from 2007/2008 to 2009/2010. There was a decline
      in open surgery for upper tract stones from 278 cases in 2000/2001 to 47 cases in
      2009/2010 (an 83% reduction). Treatment for stone disease has increased
      substantially in comparison with other urological activity. In 2009/2010, SWL was
      performed almost as frequently as transurethral resection of the prostate or
      transurethral resection of bladder tumour, ureteroscopy for stones was performed
      more frequently than nephrectomy, radical prostatectomy and cystectomy combined,
      and percutaneous nephrolithotomy was performed more frequently than cystectomy.
      CONCLUSIONS: The present study highlights the increase in prevalence and
      treatment of stone disease in the UK over the last 10 years. If this trend
      continues it has important implications for workforce planning, training, service
      delivery and research in the field of urolithiasis.

PMID- 21883852
TI  - Association between smoking cessation and sexual health in men.
AB  - OBJECTIVE: To provide the first empirical investigation of the association
      between smoking cessation and indices of physiological and subjective sexual
      health in men. SUBJECTS AND METHODS: Male smokers, irrespective of erectile
      dysfunction status, who were motivated to stop smoking ('quitters'), were
      enrolled in an 8-week smoking cessation programme involving a nicotine
      transdermal patch treatment and adjunctive counselling. Participants were
      assessed at baseline (while smoking regularly), at mid-treatment (while using a
      high-dose nicotine transdermal patch), and at a 4-week post-cessation follow-up.
      Physiological (circumferential change via penile plethysmography) and subjective
      sexual arousal indices (continuous self-report), as well as self-reported sexual
      functioning were assessed at each visit. RESULTS: Intent-to-treat analyses
      indicated that, at follow-up, successful quitters (n= 20), compared with those
      who relapsed (n= 45), showed enhanced erectile tumescence responses, and faster
      onset to reach maximum subjective sexual arousal. Although successful quitters
      displayed across-session enhancements in sexual function, they did not show a
      differential improvement compared with unsuccessful quitters. CONCLUSIONS:
      Smoking cessation significantly enhances both physiological and self-reported
      indices of sexual health in long-term male smokers, irrespective of baseline
      erectile impairment. It is hoped that these results may serve as a novel means to
      motivate men to stop smoking.

PMID- 21883853
TI  - Factors associated with ejaculatory and orgasmic dysfunction in men with erectile
      dysfunction: analysis of clinical trials involving the phosphodiesterase type 5
      inhibitor tadalafil.
AB  - OBJECTIVE: To determine frequencies of, and risk factors for, ejaculatory
      dysfunction (EjD) and orgasmic dysfunction (OD) in men with different degrees of
      erectile dysfunction (ED). PATIENTS AND METHODS: Baseline data from 28 ED trials
      were integrated and analysed. The International Index of Erectile Function
      Question 9 (IIEF-Q9; 'When you had sexual stimulation or intercourse, how often
      did you ejaculate?') and IIEF-Q10 ('How often did you have the feeling of orgasm
      with or without ejaculation?') were used to evaluate ejaculatory and orgasmic
      functions. Responses of 'almost never or never' or 'a few times (much less than
      half the time)' were taken as evidence of EjD or OD, respectively, whereas
      responses of 'almost always or always' or 'most times (much more than half the
      time)' were taken as evidence of normal function. Estimates of the relative risks
      (RRs) of EjD or OD were determined for multiple patient characteristics. RESULTS:
      Among 12,130 study participants with available data, only 5117 (42.2%) reported
      normal ejaculatory function, and 4321 (35.6%) normal orgasm, regardless of ED
      severity. Among subjects with poor ejaculatory function, 16.7% had mild ED, and
      among subjects with poor sensation of orgasm, 21.9% had mild ED. Frequencies of
      EjD and OD increased with increasing ED severity. Of the 5117 individuals with
      normal ejaculatory function, 796 (15.6%) had poor sensation of orgasm. Of the
      4321 subjects with normal orgasm, 226 (5.2%) had poor ejaculatory function. Men
      with (vs without) EjD or OD tended to be younger: 53.7 vs 56.9 years and 54.2 vs
      56.2 years, respectively. Factors associated with increased RRs of EjD and OD
      included cardiomyopathy (RR for EjD 1.74; RR for OD 1.59); cardiac failure (RR
      1.40; 1.22); and baseline use (or history of use) of antipsychotics (RR 1.45;
      1.30), selective serotonin reuptake inhibitors (RR 1.31; 1.27), and tricyclic
      antidepressants (RR 1.34; 1.28). CONCLUSIONS: EjD and OD occurred at baseline in
      more than one in three men enrolled in tadalafil trials. Even men with mild ED
      reported EjD or OD. Further studies are warranted to better understand the
      impacts of EjD and OD on male sexuality and quality of life.

PMID- 21883854
TI  - Use of a mixture of lignocaine and bupivacaine vs lignocaine alone for male
      circumcision under local anaesthesia in Rakai, Uganda.
AB  - OBJECTIVE: To assess self-reported pain control during and after surgery with a
      mixture of lignocaine and bupivacaine compared with lignocaine alone among male
      circumcision (MC) service recipients in Rakai, Uganda. PATIENTS AND METHODS: The
      two formulations of local anaesthesia for MC were used alternatively at weekly
      intervals in 360 patients; 179 received lignocaine alone and 181 received the
      lignocaine and bupivacaine mixture (LBmix). The proportions of men reporting pain
      during or after surgery, and the need for additional anaesthesia during surgery
      were determined for the LBmix vs lignocaine using Poisson adjusted rate ratios
      (RRs). Characteristics including age, weight, surgeon (medical officer vs
      clinical officer), surgical method and duration of surgery were compared between
      the arms using two-sample t-tests and chi-square tests. RESULTS: Patient and
      provider characteristics were comparable between the two anaesthetic groups. A
      higher proportion of patients reported pain during surgery in the lignocaine
      group (adjusted RR 11.6, 95% confidence interval [CI] 3.5-37.9, P < 0.001),
      required additional anaesthesia (adjusted RR 4.8, 95% CI 1.4-17.1, P = 0.015),
      and were more likely to report pain during the immediate postoperative period
      (adjusted RR 3.4, 95% CI 2.3-5.0, P < 0.001). These differences were particularly
      marked among patients with MC times longer than the median (adjusted RR 13.4, 95%
      CI 3.1-57.0, P < 0.001). CONCLUSION: The LBmix significantly reduced pain
      associated with MC and the need for additional anaesthesia during MC.

PMID- 21883855
TI  - Systematic review of surgical treatments for benign prostatic hyperplasia and
      presentation of an approach to investigate therapeutic equivalence (non
      inferiority).
AB  - OBJECTIVE: * To assess the potential additional benefit of non-standard vs
      standard surgical treatments for benign prostatic hyperplasia (BPH) and to
      present a new methodological approach to investigate therapeutic equivalence (non
      inferiority) regarding symptom reduction. PATIENTS AND METHODS: * We conducted a
      systematic review and searched MEDLINE, Embase and the Cochrane Library (last
      search: 10/2009) for randomized controlled trials (RCTs) and non-randomized
      controlled clinical trials (CCTs). * Eligible studies were those that included
      patients with symptomatic BPH requiring surgical treatment and which compared non
      standard procedures (e.g. minimally invasive technologies) with standard ones
      (e.g. transurethral resection of the prostate, TURP). In addition, only studies
      analysing patient-relevant outcomes were considered (e.g. irritative and
      obstructive symptoms, length of hospital stay, quality of life and adverse
      events). * The main outcome of interest for the present analysis was superiority
      or non-inferiority for symptom reduction. * As no trial investigated non
      inferiority, we defined a non-inferiority threshold (0.25 standard deviation) on
      the basis of published literature. If a non-standard procedure showed non
      inferiority for symptom reduction, additional outcomes were assessed. Meta
      analyses were conducted if feasible and meaningful. RESULTS: * In all, 43 mainly
      low-quality trials (RCTs only) compared nine non-standard surgical treatments
      with standard ones. * Mean follow-up ranged from 6 to 84 months. * No non
      standard procedure was superior for symptom reduction. Non-inferiority for
      symptom reduction was shown in patients who had undergone holmium laser resection
      of the prostate (HoLRP) or thulium laser resection of the prostate (TmLRP). * As
      procedural advantages (e.g. no occurrence of transurethral resection syndrome)
      and other advantages (e.g. shortened hospital stay) were found, an indication of
      an additional benefit of HoLRP and TmLRP was determined. CONCLUSIONS: * No proof
      of superiority for symptom reduction has been shown for non-standard surgical
      treatments in patients with BPH. * There is a lack of high-quality RCTs and
      trials designed to investigate non-inferiority. * Future studies should define a
      non-inferiority threshold (ideally, uniform) a priori, so that results of
      individual studies are interpretable and comparable, and future systematic
      reviews should consider this issue.

PMID- 21883856
TI  - Incidence and outcomes of ductal carcinoma of the prostate in the USA: analysis
      of data from the Surveillance, Epidemiology, and End Results program.
AB  - OBJECTIVE: To use the national Surveillance, Epidemiology, and End Results (SEER)
      cancer registry to describe the natural history, national incidence and treatment
      patterns for ductal prostate cancer (PCa) over the last 20 years, as the
      available literature on ductal PCa is limited to small case series because of few
      patient numbers. PATIENTS AND METHODS: From the SEER registry, 693 men with
      ductal PCa were identified from 1970. The demographics, clinical features and
      cause of death data were collected from men with ductal and acinar histological
      types. RESULTS: The incidence of ductal PCa has increased over each decade, but
      the overall percentage of ductal relative to acinar PCa has remained stable. Men
      with ductal PCa were more likely to present with advanced disease (30% T3 with
      ductal PCa, compared with 7% with acinar PCa). Men with ductal PCa underwent
      similar rates of radical surgery, lower rates of radiotherapy but a higher
      frequency of outlet (transurethral resection) procedures. Men with ductal PCa had
      a significantly greater rate of death from PCa (12% vs 4%) than men with acinar
      PCa. Comparing PCa-specific mortality, men with ductal PCa had similar rates of
      death to men with Gleason 4 + 4 grade acinar PCa. CONCLUSIONS: Despite a stable
      incidence, ductal PCa remains an aggressive PCa usually presenting with advanced
      clinical stage and resulting in a high rate of PCa-specific mortality similar to
      Gleason 4 + 4 acinar PCa. Patients would probably benefit from combined
      modalities including radical surgery, radiotherapy and palliative outlet
      procedures.

PMID- 21883857
TI  - Survival of patients with small cell carcinoma of the prostate during 1973-2003:
      a population-based study.
AB  - OBJECTIVE: To describe the survival of patients with primary small cell carcinoma
      (SCC) of the prostate and assess prognostic factors based on a large population
      sample. PATIENTS AND METHODS: A total of 241 cases of SCC of the prostate were
      reported to the Surveillance, Epidemiology, and End Results (SEER) registries
      from 1973 to 2003 of which 191 cases were included in our study. We used the
      Kaplan-Meier method for estimating survival, and Cox proportional hazard
      regression modelling to evaluate prognostic variables. RESULTS: The overall age
      adjusted incidence rate was 0.278 per 1,000,000 (95% confidence interval, 0.239
      0.323). In all, 60.5% presented as metastatic disease compared with 39.5% who
      presented as local/regional disease (P= 0.012). The 12, 24, 36, 48 and 60 months
      observed survival rates were 47.9%, 27.5%, 19%, 17% and 14.3% respectively. On
      univariate analyses, age <60, concomitant low-grade prostatic adenocarcinoma,
      absence of metastasis, prostatectomy and radiation therapy were favourable
      prognostic factors. In multivariate regression modelling, age, pathology and
      stage were strong predictors of survival. CONCLUSIONS: Using the SEER database,
      we present the largest study describing the epidemiology of primary SCC of the
      prostate. We found age, concomitant low-grade prostatic adenocarcinoma, and stage
      of the disease to be the strongest predictors of survival for patients with
      prostatic SCC. Future studies evaluating a broader range of clinical and
      molecular markers are needed to refine the prognostic model of this relatively
      rare disease.

PMID- 21883858
TI  - Early comparison of nephrectomy options in children (open, transperitoneal
      laparoscopic, laparo-endoscopic single site (LESS), and robotic surgery).
AB  - OBJECTIVE: To compare the perioperative parameters of paediatric patients who
      underwent nephrectomy via laparo-endoscopic single site (LESS) surgery (also
      known as single incision laparoscopic surgery or SILS) with those who underwent
      nephrectomy via conventional laparoscopy (LAP), robotic-assisted laparoscopy
      (RALN), and open surgery (OPEN). PATIENTS AND METHODS: The medical records of 69
      paediatric patients at a single institution who underwent nephrectomies for non
      functioning kidneys in 72 renal units (39 OPEN, 11 LAP, 11 RALN and 11 LESS) were
      reviewed for patient demographics and perioperative clinical parameters. RESULTS:
      The minimally invasive modalities in children, including LESS nephrectomy, were
      associated with shorter lengths of hospital stay (P < 0.001) and decreased
      postoperative pain medication usage (P < 0.001) than with open surgery. Similar
      surgical times were noted with LESS and the other minimally invasive modalities
      (LAP and RALN) (P= 0.056). However, the minimally invasive modalities (LESS, LAP
      and RALN) were associated with slightly longer surgical times when compared with
      open surgery (P < 0.001), which may, in part, be secondary to learning curve
      factors. No differences were noted among the minimally invasive modalities for
      postoperative pain medication usage (P= 0.354) and length of hospital stay (P=
      0.86). CONCLUSIONS: The minimally invasive modalities for nephrectomy in
      children, including LESS nephrectomy, are associated with shorter lengths of
      hospital stay and decreased postoperative pain medication use when compared with
      open surgery. LESS nephrectomy in children is associated with similar surgical
      times, lengths of hospital stay and postoperative pain medication use as the
      other minimally invasive modalities (LAP and RALN). Slightly longer surgical
      times are noted with the minimally invasive modalities, including LESS
      nephrectomy, when compared with open surgery, which may, in part, be secondary to
      learning curve factors.

PMID- 21883859
TI  - Photoselective vaporization of the prostate: pursuing good indications based on
      the results of 400 Japanese patients.
AB  - OBJECTIVE: To investigate good indications of photoselective vaporization of the
      prostate (PVP) by retrospective evaluation of its efficacy in relation to
      prostate volume. PATIENTS AND METHODS: A cohort of 400 patients had International
      Prostate Symptoms Score (IPSS), Quality of Life (QoL) score, urinary peak flow
      (Q(max) ), and prostate volume (P(vol) ), assessed before and after surgery.
      Changes of outcome variables were compared among four groups classified according
      to preoperative prostate volume: <30 mL (group A), >=30 and <50 mL (group B),
      >=50 and <70 mL (group C), and >70 mL (group D). RESULTS: Operating times and
      amounts of energy applied were 44.2 min and 159 kJ, 67.7 min and 268 kJ, 111 min
      and 409 kJ, and 171 min and 604 kJ in groups A, B, C, and D, respectively. All
      variables improved significantly and immediately, and remained for more than 12
      months. Investigation of groups classified by prostate size demonstrated that
      IPSS and QoL score decreased and improvement rate of Q(max) rose as prostate
      volume increased. Changes of P(vol) were from 24.5 mL to 13.2 mL (-46.1%), from
      39.8 mL to 22.9 mL (-42.4%), from 58.4 mL to 32.8 mL (-43.8%), and from 92.1 mL
      to 53.8 mL (-41.5%) in groups A, B, C, and D, respectively. Overall the P(vol)
      reduction rate was 43.2%, and no significant differences were observed in
      reduction ratios among the groups. Complications were minimal, but bladder neck
      contracture arose in 16 cases with a smaller prostate. CONCLUSION: Whilst the
      percentage reduction in volume was similar across the groups, the larger absolute
      volume reduction in patients with larger prostates was associated with greater
      improvement in objective urinary function variables, and with symptom score
      reduction.

PMID- 21883860
TI  - Bilateral pudendal afferent stimulation improves bladder emptying in rats with
      urinary retention.
AB  - OBJECTIVE: To determine whether bilateral electrical stimulation (BiES) of the
      transected pudendal sensory nerves could further enhance the voiding efficiency
      beyond that produced by unilateral electrical stimulation (UniES) of transected
      pudendal afferents in rats with urinary retention. MATERIALS AND METHODS: The
      efficiency of bladder emptying with either UniES or BiES of pudendal nerve
      afferents was measured after acute bilateral transection of the sensory branch of
      the pudendal nerve. The effects of UniES and BiES on voiding in a partially
      denervated bladder and acute spinal transection, respectively, were determined.
      RESULTS: The voiding efficiency (VE) was reduced from 69 to 22% after bilateral
      transection of the sensory branch of the pudendal nerve. UniES or BiES increased
      the VE to 49-62%. Although in most instances BiES consistently generated more
      efficient bladder emptying than did UniES, these differences were not
      significant. Both UniES and BiES increased VE after unilateral pelvic nerve
      transection, demonstrating efficacy in a partially denervated bladder. The
      enhancement of VE by either UniES or BiES was preserved after acute T(9)-T(10),
      demonstrating the spinal origin of this augmenting reflex. CONCLUSIONS: The
      results of the present study are consistent with an essential role for pudendal
      sensory feedback in efficient bladder emptying, and unilateral and bilateral
      electrical activation of pudendal nerve afferents are equally efficient in
      improving bladder emptying in an animal model of urinary retention. This could
      provide an approach to improve bladder emptying in patients with non-obstructive
      urinary retention.

PMID- 21883861
TI  - The changing pattern of antimicrobial resistance within 42,033 Escherichia coli
      isolates from nosocomial, community and urology patient-specific urinary tract
      infections, Dublin, 1999-2009.
AB  - OBJECTIVE: To investigate the changing pattern of antimicrobial resistance in
      Escherichia coli urinary tract infection over an eleven year period, and to
      determine whether E. coli antibiotic resistance rates vary depending on whether
      the UTI represents a nosocomial, community acquired or urology patient specific
      infection. PATIENT AND METHODS: A retrospective analysis of the 42,033 E. coli
      urine isolates from the 11-year period 1999-2009 in a single Dublin teaching
      hospital was performed. WHONET(TM) software was used to analyse the changing
      pattern of sensitivity and resistance of E. coli to commonly used antibiotics
      over the study period. The origins of the urine samples were stratified into
      three groups: inpatients with nosocomial UTIs; urine originating from the
      emergency department and general practice (community UTIs); and UTIs in urology
      patients. RESULTS: Urinary tract infections in the urology patient population
      demonstrate higher antibiotic resistance rates than nosocomial or community UTIs.
      There were significant trends of increasing resistance over the 11-year period
      for ampicillin, trimethoprim, gentamicin and ciprofloxacin, and significant
      differences in co-amoxyclav, gentamicin, nitrofurantion and ciprofloxacin
      resistance rates depending on the sample origin. Ampicillin and trimethoprim were
      the least active agents against E. coli, with total 11-year resistance rates of
      58.3 and 33.8%, respectively. The overall gentamicin resistance rate was 3.4% and
      is climbing at a rate of 0.7% per year (P < 0.001). Within the urology patient
      population the resistance rate was 6.4%. Ciprofloxacin resistance approaches 20%
      in the nosocomial UTI population and approaches 30% in the urology population;
      however, it remains a reasonable empirical antibiotic choice in this community,
      with an 11-year resistance rate of 10.6%. CONCLUSIONS: E. coli remains the
      commonest infecting uropathogen in the community and hospital setting with its
      incidence climbing from 50 to 60% of UTIs over the 11-year period. Neither
      penicillins nor trimethoprim represent suitable empirical antimicrobials for UTI
      and ciprofloxacin resistance in this Dublin-based study renders it unsuitable
      empirical therapy for nosocomial UTIs and UTIs in the urology population. The
      dramatic 11-year rate increase in gentamicin resistance is of paramount concern.

PMID- 21883862
TI  - The effect of intracrystalline and surface-bound osteopontin on the attachment of
      calcium oxalate dihydrate crystals to Madin-Darby canine kidney (MDCK) cells in
      ultrafiltered human urine.
AB  - OBJECTIVE: To determine the effects of intracrystalline (IC), surface-bound (SB)
      and combined IC + SB osteopontin (OPN) on the binding of urinary calcium oxalate
      dihydrate (COD) crystals to Madin-Darby canine kidney (MDCK-II) cells in
      ultrafiltered (UF) human urine. MATERIALS AND METHODS: (14)C-oxalic acid-labelled
      urinary COD crystals containing IC OPN were generated in pooled UF human urine
      containing human milk OPN at concentrations of 0, 1.0 and 5.0 mg/L. Additional
      labelled crystals were nucleated from a separate sample of the same pooled UF
      urine, to which were later added the same amounts of protein to produce crystals
      with SB OPN. COD crystals with IC+SB OPN were prepared using a combination of
      both techniques. Control crystals were prepared in the absence of OPN. Crystals
      were incubated with MDCK-II cells for up to 180 min in UF urine adjusted to 8 mm
      Ca(2+). Binding values for individual concentrations at specific time points and
      overall differences between binding curves were compared using the Mann-Whitney U
      test. Crystal morphology and attachment to the cells were confirmed using field
      emission scanning electron microscopy (FESEM). RESULTS: The sizes of crystals
      precipitated from UF urine in the presence of 0, 1 and 5 mg/L OPN were 21.9 um,
      19.3 um and 16.5 um, indicating that OPN had inhibited crystal growth in a dose
      dependent fashion. Binding curves for control crystals were smooth, while those
      of the IC and IC+SB COD crystals associated with 1 and 5 mg/L OPN were bimodal,
      as were those of the 1 mg/L SB crystals. This suggests that OPN induces or
      potentiates a transient response that enables MDCK-II cells to release COD
      crystals after they have attached. Although OPN generally reduced the binding of
      urinary COD crystals to MDCK-II cells, at times it also appeared to mediate
      adhesion. It is possible therefore that OPN can reduce or increase crystal
      binding, and that our data represent the net effect of its opposing inhibitory or
      promotory properties. CONCLUSIONS: In UF urine, OPN inhibits the growth of COD
      crystals and reduces the binding of urinary COD crystals to MDCK-II cells,
      regardless of whether it is IC, SB, or IC+SB. Future studies aimed at clarifying
      the effects of OPN, or indeed any urinary component, on crystal-cell interaction,
      should use crystals precipitated from urine and be performed under urinary
      conditions.

PMID- 21883863
TI  - Prognostic significance of preoperative kidney volume for predicting renal
      function in renal cell carcinoma patients receiving a radical or partial
      nephrectomy.
AB  - Study Type - Prognosis (case series) Level of Evidence 4 What's known on the
      subject? and What does the study add? At present, many studies have been executed
      to identify predictors for chronic kidney disease or renal insufficiency after
      radical nephrectomy or partial nephrectomy. We examined whether preoperative
      kidney volume is a predictor for renal function after radical or partial
      nephrectomies in RCC patients. To our knowledge, this is the first study to
      report on the relationship between preoperative kidney volume and changes in
      renal function in RCC patients who underwent radical nephrectomy or partial
      nephrectomy performed by one surgeon. OBJECTIVE: To investigate whether
      preoperative kidney volume is a prognostic factor for predicting the
      postoperative glomerular filtration rate (GFR) in renal cell carcinoma (RCC)
      patients. PATIENTS AND METHODS:   We included 133 patients who underwent radical
      (n= 83) or partial (n= 50) nephrectomy for RCC. Kidney parenchymal volume was
      measured using personal computer-based software and GFR was estimated before and
      after surgery at 6 and 12 months. We evaluated the change in kidney volume after
      radical and partial nephrectomy and used regression analysis to identify
      predictors of lower post-surgical GFR at 12 months. RESULTS: The mean volume of
      the normal side kidney for the radical nephrectomy group increased from 142.4 mL
      to 166.0 mL (17.2%) and 171.5 mL (21.2%) after surgery at 6 and 12 months,
      respectively. In the partial nephrectomy group, the volume of the normal side
      kidney increased from 127.2 mL to 138.8 mL (9.1%) and 140.6 mL (10.9%) after
      surgery at 6 and 12 months, respectively. The volume of the operated side kidney
      decreased from 128.5 mL to 102.3 mL (20.1%) and 101.8 (20.6%) after surgery at 6
      and 12 months, respectively. In the radical nephrectomy group, older age (P <
      0.001), preoperative volume of the normal kidney (P= 0.022) and preoperative GFR
      for the normal side kidney (P= 0.045) were significant predictors of lower post
      surgical GFR at 12 months. In the partial nephrectomy group, older age (P= 0.001)
      and preoperative volume for both kidneys (P= 0.037) were significant predictors
      of lower post-surgical GFR at 12 months. CONCLUSION: Preoperative kidney volume
      is an independent predictor of GFR in RCC patients who underwent radical or
      partial nephrectomy.

PMID- 21883864
TI  - Clinical efficacy and prognostic factors for overall survival in Japanese
      patients with metastatic renal cell cancer treated with sunitinib.
AB  - Study Type--Therapy (case series). Level of Evidence 4. What's known on the
      subject? and What does the study add? A randomized prospective phase III clinical
      trial for systemic treatment-naive metastatic renal cell cancer (RCC) patients
      demonstrated the superiority of sunitinib over interferon with an acceptable
      safety profile. However, a commonly asked question is whether patients with RCC
      in clinical trials are representative of those with this disease being seen in
      ordinary clinical practice. To our knowledge, this is the first report of
      sunitinib for the Japanese patients with metastatic RCC in ordinary clinical
      practice. The estimated median PFS and OS in this study were 9.3 and 32.2 months,
      respectively. The application of the MSKCC model distinctly separated OS curves
      (P<0.001), suggesting that MSKCC prognostic factors might be still valid to
      predict survival in metastatic RCC in the era of molecular targeted therapy.
      OBJECTIVES: * To report the treatment efficacy and safety profile of sunitinib
      for patients with metastatic renal cell carcinoma (RCC) in ordinary clinical
      practice. * In addition, to investigate the prognostic clinicopathological
      factors in these patients. PATIENTS AND METHODS: * The present study consisted of
      native Japanese patients with metastatic RCC, comprising 29 pretreated and 34
      systemic treatment-naive patients. * Univariate and multivariate analyses were
      performed by the log-rank test and the Cox proportional hazards model,
      respectively. RESULTS: * Estimated median progression-free survival and overall
      survival (OS) were 9.3 months (95% confidence interval, CI, 5.0-13.7) and 32.2
      months (95% CI, 24.4-40.0), respectively. * Among the patients pretreated before
      sunitinib, two patients were treated with initialized systemic therapy with
      sorafenib and the remaining 27 were initialized with interferon-alpha. * The OS
      from the initial systemic therapy of the patients in pretreated groups was 79.6
      months (95% CI, 14.6-144.5). * The application of the Memorial Sloan-Kettering
      Cancer Center model distinctly separated the OS curves (P < 0.001). * The most
      common grade 3 adverse events were fatigue (53%), thrombocytopaenia (48%), hand
      foot syndrome (16%), anaemia (20%), hypertension (10%) and leucopaenia (9%),
      although these events were manageable and reversible. CONCLUSIONS: * Sunitinib
      has a favourable efficacy/safety profile for Japanese metastatic RCC patients in
      clinical practice. * The estimated median OS was >2 years with acceptable
      tolerability. * The median OS from the initial systemic therapy of the pretreated
      patients was >6 years. * Memorial Sloan-Kettering Cancer Center prognostic
      factors still appear to be valid for predicting survival in metastatic RCC in the
      era of molecular targeted therapy.

PMID- 21883865
TI  - Early comparison of nephrectomy options in children (open, transperitoneal
      laparoscopic, laparo-endoscopic single site (LESS), and robotic surgery).

PMID- 21883867
TI  - Components of oviduct physiology in eutherian mammals.
AB  - Recalling the evolutionary sequence of development first of gonad and
      subsequently of oviducts, ovarian endocrine regulation of all known components of
      oviduct physiology is reviewed. Ovaries not only influence oviducts via the
      systemic blood circulation, but also locally by counter-current transfer of
      relatively high concentrations of steroid hormones and prostaglandins between the
      ovarian vein and oviduct branch of the ovarian artery. The efficiency and impact
      of such counter-current transfer is greatest around the time of ovulation, the
      transfer process receiving further inputs from hormones present in peritoneal
      fluid. Classical oviduct physiology is summarised, and the potential molecular
      consequences of temperature gradients within the duct lumen examined. At
      ovulation, an oocyte-cumulus complex is displaced in minutes from the follicular
      surface to the site of fertilisation at the ampullary-isthmic junction of the
      oviduct. This rapid initial phase is contrasted with the subsequent slow
      progression of embryos to the uterus in days, still encompassed within a zona
      pellucida. Regarding transport of spermatozoa, the formation of a pre-ovulatory
      reservoir in the caudal portion of the oviduct isthmus is noted, with suppression
      of motility and sperm-head binding to epithelial organelles acting to maintain
      fertilising ability. Completion of capacitation is prompted shortly before
      ovulation, predominantly by Ca(2+)  influx into bound spermatozoa. A controlled
      release of spermatozoa coupled with their hyperactivation results in initial
      sperm:egg ratios at the site of fertilisation close to unity, thereby avoiding
      the pathological condition of polyspermy. Both the oviduct milieu and embryonic
      development are influenced by paracrine activity of follicular granulosa cells
      released at ovulation and remaining in suspension in the vicinity of the oocyte
      or embryo. These cells may amplify early pregnancy signals from a zygote to the
      endosalpinx. Beneficial effects of the oviduct on domestic animal embryos are
      contrasted with anomalies arising as a consequence of in vitro culture. Primate
      embryos do not require exposure to an oviduct for normal development, perhaps due
      to overlapping compositions of endosalpingeal and endometrial secretions.
      Additionally, primate endometrial secretions may be modified by viable gametes or
      an embryo in the presence of a cumulus cell suspension.

PMID- 21883866
TI  - Characterization of polygenic resistance to powdery mildew in tomato at
      cytological, biochemical and gene expression level.
AB  - Extensive research in the area of plant innate immunity has increased
      considerably our understanding of the molecular mechanisms associated with
      resistance controlled by a dominant resistance gene. In contrast, little is known
      about the molecular basis underlying the resistance conferred by quantitative
      trait loci (QTLs). In this study, using the interaction of tomato (Solanum
      lycopersicum) with Oidium neolycopersici, we compared the cytological,
      biochemical and molecular mechanisms involved in both monogenic and polygenic
      resistances conferred by a dominant gene (Ol-1) and three QTLs (Ol-qtls),
      respectively. Our results showed that the three Ol-qtls jointly confer a very
      high level of broad-spectrum resistance and that the resistance is associated
      with both the hypersensitive response and papillae formation, with the
      hypersensitive response being prevalent. Both H(2)O(2) and callose accumulation,
      which are coupled with Ol-1-mediated resistance, are also associated with the
      resistance conferred by Ol-qtls. Further, we analysed the pathogen-induced
      transcript profiles of near-isogenic lines carrying the three Ol-qtls and the Ol
      1 gene. Transcript profiles obtained by cDNA-amplified fragment length
      polymorphism analysis showed that, on fungal challenge, about 70% of the
      transcript-derived fragments are up-regulated in both susceptible and resistant
      genotypes. Most of the sequenced transcript-derived fragments showed homology to
      genes with functions in defence responses, suggesting that defence-responsive
      genes responsible for basal defence are involved in both monogenic and polygenic
      resistances conferred by Ol-1 and Ol-qtls, respectively. Although about 18% of
      the identified transcript-derived fragments are specific for either monogenic or
      polygenic resistance, their expression patterns need to be further verified by
      quantitative reverse transcriptase-polymerase chain reaction.

PMID- 21883868
TI  - Robust production of virus-like particles and monoclonal antibodies with
      geminiviral replicon vectors in lettuce.
AB  - Pharmaceutical protein production in plants has been greatly promoted by the
      development of viral-based vectors and transient expression systems. Tobacco and
      related Nicotiana species are currently the most common host plants for the
      generation of plant-made pharmaceutical proteins (PMPs). Downstream processing of
      target PMPs from these plants, however, is hindered by potential technical and
      regulatory difficulties owing to the presence of high levels of phenolics and
      toxic alkaloids. Here, we explored the use of lettuce, which grows quickly yet
      produces low levels of secondary metabolites and viral vector-based transient
      expression systems to develop a robust PMP production platform. Our results
      showed that a geminiviral replicon system based on the bean yellow dwarf virus
      permits high-level expression in lettuce of virus-like particles (VLP) derived
      from the Norwalk virus capsid protein and therapeutic monoclonal antibodies
      (mAbs) against Ebola and West Nile viruses. These vaccine and therapeutic
      candidates can be readily purified from lettuce leaves with scalable processing
      methods while fully retaining functional activity. Furthermore, this study also
      demonstrated the feasibility of using commercially produced lettuce for high
      level PMP production. This allows our production system to have access to
      unlimited quantities of inexpensive plant material for large-scale production.
      These results establish a new production platform for biological pharmaceutical
      agents that are effective, safe, low cost, and amenable to large-scale
      manufacturing.

PMID- 21883870
TI  - Systematic review on the financial return of worksite health promotion programmes
      aimed at improving nutrition and/or increasing physical activity.
AB  - This systematic review summarizes the current evidence on the financial return of
      worksite health promotion programmes aimed at improving nutrition and/or
      increasing physical activity. Data on study characteristics and results were
      extracted from 18 studies published up to 14 January 2011. Two reviewers
      independently assessed the risk of bias of included studies. Three metrics were
      (re-)calculated per study: the net benefits, benefit cost ratio (BCR) and return
      on investment (ROI). Metrics were averaged, and a post hoc subgroup analysis was
      performed to compare financial return estimates between study designs. Four
      randomized controlled trials (RCTs), 13 non-randomized studies (NRSs) and one
      modelling study were included. Average financial return estimates in terms of
      absenteeism benefits (NRS: ROI 325%, BCR 4.25; RCT: ROI -49%, BCR 0.51), medical
      benefits (NRS: ROI 95%, BCR 1.95; RCT: ROI -112%, BCR -0.12) or both (NRS: ROI
      387%, BCR 4.87; RCT: ROI -92%, BCR 0.08) were positive in NRSs, but negative in
      RCTs. Worksite health promotion programmes aimed at improving nutrition and/or
      increasing physical activity generate financial savings in terms of reduced
      absenteeism costs, medical costs or both according to NRSs, whereas they do not
      according to RCTs. Since these programmes are associated with additional types of
      benefits, conclusions about their overall profitability cannot be made.

PMID- 21883869
TI  - Lightening the load? A systematic review of community pharmacy-based weight
      management interventions.
AB  - The extent to which community pharmacies can increase capacity for weight
      management is unknown. Thus, the objective of the present paper was to evaluate
      the effectiveness and cost-effectiveness of community pharmacy weight management
      interventions. This paper used a design of systematic review and narrative
      synthesis. Electronic databases (1999-2009) were searched, including Medline,
      EMBASE, CINAHL and Pharm-line. Weight management studies in community pharmacies
      were eligible for the inclusion criteria. All languages and study designs were
      considered. Outcome measures included body weight or anthropometry (at baseline
      and at least one follow-up time point). Data were extracted through independent,
      duplicate data extraction and quality assessment. As a result, 10 studies were
      included, totalling 2,583 service users and 582 pharmacies from the USA, the UK,
      Switzerland, Spain and Denmark. One was a randomized controlled trial of a meal
      replacement versus a reduced calorie diet. A non-randomized controlled before and
      after study compared community pharmacist treatment using Orlistat with usual
      care. Eight studies were uncontrolled. Five studies described behaviour change
      techniques. Long-term (12 months) mean weight loss measured in three studies
      ranged from 1.1 to 4.1 kg. Four uncontrolled studies reported statistically
      significant weight loss. No study reported economic evaluations. Currently, there
      is insufficient evidence for the effectiveness and cost-effectiveness of
      community pharmacy-based weight management initiatives to support investment in
      their provision.

PMID- 21883871
TI  - The benefits of bariatric surgery in obese patients with hip and knee
      osteoarthritis: a systematic review.
AB  - Osteoarthritis is a common progressive disease leading to joint pain and severe
      disability. It is a complex multifactorial disease leading to damage of
      cartilage, deposition of subchondral bone matrix and release of pro-inflammatory
      cytokines. Obesity is an emerging epidemic and also an important risk factor for
      osteoarthritis. Weight loss has been shown to improve pain and function in hip
      and knee joints with osteoarthritis. Bariatric surgery currently is the only
      evidence-based approach to marked weight loss in obese individuals. However,
      there is currently limited literature to evaluate the role of bariatric surgery
      in hip and knee osteoarthritis. The objective of the present study was to
      systematically review the literature regarding the effectiveness of bariatric
      surgery in obese adult patients in improving large weight-bearing joint (hip and
      knee) osteoarthritis. Published English-language manuscripts were considered for
      review inclusion. A comprehensive search of electronic databases using broad
      search terms was completed. From a total of 400 articles, eight articles were
      identified. A total of six studies were included for qualitative analysis. A
      general trend was identified indicating improved hip and knee osteoarthritis
      following marked weight loss secondary to bariatric surgery. This systematic
      review demonstrates that bariatric surgery may benefit obese patients with hip or
      knee osteoarthritis. However, this review identifies the need for randomized
      controlled trials to clarify the role and indications for bariatric surgery.

PMID- 21883872
TI  - Perinatal morbidity associated with late preterm deliveries compared with
      deliveries between 37 and 40 weeks of gestation.
AB  - OBJECTIVE: To estimate the risk of short-term complications in neonates born
      between 34 and 36 weeks of gestation. DESIGN: This is a retrospective cohort
      study. SETTING: Deliveries in 2005 in the USA. POPULATION: Singleton live births
      between 34 and 40 weeks of gestation. METHODS: Gestational age was subgrouped
      into 34, 35, 36 and 37-40 completed weeks of gestation. Statistical comparisons
      were performed using chi-square test and multivariable logistic regression
      models, with 37-40 weeks of gestation designated as referent. MAIN OUTCOME
      MEASURES: Perinatal morbidities, including 5-minute Apgar scores, hyaline
      membrane disease, neonatal sepsis/antibiotics use, and admission to the intensive
      care unit. RESULTS: In all, 175,112 neonates were born between 34 and 36 weeks in
      2005. Compared with neonates born between 37 and 40 weeks, neonates born at 34
      weeks had higher odds of 5-minute Apgar <7 (adjusted odds ratio [aOR] 5.51, 95%
      CI 5.16-5.88), hyaline membrane disease (aOR 10.2, 95% CI 9.44-10.9), mechanical
      ventilation use >6 hours (aOR 9.78, 95% CI 8.99-10.6) and antibiotic use (aOR
      9.00, 95% CI 8.43-9.60). Neonates born at 35 weeks were similarly at risk of
      morbidity, with higher odds of 5-minute Apgar <7 (aOR 3.42, 95% CI 3.23-3.63),
      surfactant use (aOR 3.74, 95% CI 3.21-4.22), ventilation use >6 hours (aOR 5.53,
      95% CI 5.11-5.99) and neonatal intensive-care unit admission (aOR 11.3, 95% CI
      11.0-11.7). Neonates born at 36 weeks remain at higher risk of morbidity compared
      with deliveries at 37-40 weeks of gestation. CONCLUSIONS: Although the risk of
      undesirable neonatal outcomes decreases with increasing gestational age, the risk
      of neonatal complications in late preterm births remains higher compared with
      infants delivered at 37-40 weeks of gestation.

PMID- 21883873
TI  - Clinical characteristics of well women seeking labial reduction surgery: a
      prospective study.
AB  - OBJECTIVE: To assess clinical characteristics and expectations in well women
      requesting elective labial reduction surgery. DESIGN: Prospective study of women
      attending an outpatient gynaecology clinic. SETTING: General gynaecology clinic
      at a Central London teaching hospital. SAMPLE: Women requesting labial reduction
      surgery and referred by their general practitioner. METHODS: The labia minora
      width and length were measured for all participants for comparison with published
      normal values. The presenting complaint was recorded, along with demographic
      details, expectations of surgery and sources of information regarding appearance
      of the labia. MAIN OUTCOME MEASURES: Labial measurements, reported symptoms and
      expectations of surgery. RESULTS: The labia of all participants were within
      normal published limits, with a mean (SD) of 26.9 (12.8) mm (right labia), and
      24.8 (13.1) mm (left labia). The majority of complaints were regarding appearance
      or discomfort. Expectations were to alter the appearance with surgery.
      CONCLUSIONS: All women seeking surgery had normal-sized labia minora. Clear
      guidance is needed for clinicians on how best to care for the worried well woman
      seeking surgery.

PMID- 21883874
TI  - Randomized double-blind sham-controlled crossover study of short-term effect of
      percutaneous electrical nerve stimulation in neuropathic pain.
AB  - BACKGROUND: Percutaneous electrical nerve stimulation (PENS) is an electrical
      neuromodulation technique that has shown its therapeutic potential in various
      chronic pain conditions over the past few years, but well-blinded controlled
      studies are lacking. PATIENTS AND METHODS: A randomized double-blind sham
      controlled crossover trial on 31 patients with chronic pain with surface
      hyperalgesia to investigate the efficacy of PENS. RESULTS: For the active PENS
      therapies, the median numerical rating scale (NRS) for pain changed from 7.5
      (standard deviation [SD] +/- 1) (range 6-10) before therapy to 0.5 (range 0-8.5)
      after therapy (Z = -4.206, P < 0.0005 [two-tailed]). The mean pain pressure
      threshold (PPT) measured with the von Frey aesthesiometer changed from 202 gm (SD
      +/- 137 gm) (range 55-800 gm) before therapy to 626 gm (SD +/- 228 gm) (range 45
      800 gm) after therapy (Z = -4.373, P < 0.0005 [two-tailed]). There was a
      statistically significant difference between the changes in NRS for the active
      (3.9 [+/-3.2][0-8]) compared with the sham (0.1 [+/-0.4][0-1.5]) therapies, U =
      40, Z = -3.484, P < 0.0001 (two-tailed). There was a statistically significant
      difference between the changes in PPT for the active (310 gm [+/-267 gm][0-670
      gm]) compared with the sham (8 gm [+/-4 gm][0-15 gm]) therapies, U = 48.5, Z = 
      2.699, P = 0.007 (two-tailed). CONCLUSION: PENS therapy appears to be effective
      in providing short-term pain relief in chronic pain conditions. Studies,
      involving larger sample sizes and longer follow-up are recommended.

PMID- 21883875
TI  - Brazilian Portuguese validation of the Leeds Assessment of Neuropathic Symptoms
      and Signs for patients with chronic pain.
AB  - BACKGROUND: Neuropathic pain (NP) is a very frequent and unrecognized condition
      in clinical practice. Therefore, it is important to have a reliable instrument to
      assess pain subtypes in various cultures. The Leeds Assessment of Neuropathic
      Symptoms and Signs (LANSS) has been widely used and validated in many countries.
      Up to now, there has been no reliability study of this instrument in Brazil.
      METHODS: The scores of the Brazilian Portuguese version of the LANSS were studied
      in a sample of 90 chronic pain outpatients from southern Brazil. LANSS was
      translated into Portuguese and then back translated to English. Intraclass
      correlation coefficient (ICC) and internal consistency (IC) were estimated. The
      intensity of pain complaints, other demographic data, and LANSS scores
      distribution according to pain subtypes (nociceptive, neuropathic, and mixed)
      were also evaluated. RESULTS: The Brazilian Portuguese version of the LANSS
      showed good ICC (r = 0.97) and IC (Cronbach's alpha = 0.67 for total LANSS
      score). Patients with NP provided significant higher LANSS scores (19.1 +/- 3.3)
      in comparison with those with nociceptive (7.3 +/- 4.5) and mixed (13.9 +/- 3.7)
      types of pain. CONCLUSIONS: This LANSS version was found to be a reliable
      instrument for the evaluation of pain complaints due to a variety of causes. The
      profile of pain scores was similar to that observed in other countries.

PMID- 21883876
TI  - Measuring the pain impact in adults with a chronic pain condition: adaptation and
      validation of the Pain Impact Questionnaire (PIQ-6) to the Portuguese culture.
AB  - OBJECTIVE: The aim of this study was to validate the Pain Impact Questionnaire
      (PIQ-6) for Portuguese adults with a chronic pain condition. DESIGN: The
      Portuguese version was developed through forward-backward translations and a
      cognitive debriefing with chronic pain patients. A subsequent sample of patients
      was selected to test the validity and the obtained Portuguese measure. PATIENTS
      AND SETTING: Patients are comprised of a sample of 104 physical therapy patients
      with chronic pain from four outpatient clinics. OUTCOMES MEASURES: Reliability
      and validity were tested by administering the PIQ-6, the Medical Outcomes Study
      12-Item Short Form (SF-12) questionnaire, a numerical rating pain scale, and a
      form to collect some of the characteristics of the patients. RESULTS: After
      obtaining the semantic and content equivalence, the Portuguese version of PIQ-6
      showed good levels of reproducibility (intraclass correlation coefficient between
      0.82 and 0.94) and good levels of internal consistency, with Cronbach's alpha of
      0.92. The factor analysis confirmed the unidimensionality of the measure (initial
      eigen-value = 4.29, 71.6%). Construct validity was supported by the correlations
      obtained with a numerical rating pain scale (rho = 0.705), SF-12 subscales (r = 
      0.723 and -0.656), and the age of the patients (r = 0.274). CONCLUSION: The PIQ-6
      proved to be equivalent in both cultures (American/Portuguese), and is useful,
      reliable, and valid for use in Portugal.

PMID- 21883877
TI  - Comparison of 'time within therapeutic INR range' with 'percentage INR within
      therapeutic range' for assessing long-term anticoagulation control in children: a
      rebuttal.

PMID- 21883878
TI  - Fondaparinux treatment of acute heparin-induced thrombocytopenia confirmed by the
      serotonin-release assay: a 30-month, 16-patient case series.
AB  - BACKGROUND: Fondaparinux is theoretically an attractive agent for the treatment
      of immune heparin-induced thrombocytopenia (HIT), a prothrombotic disorder caused
      by platelet-activating anti-platelet factor 4/heparin antibodies. Although
      reports of the use of fondaparinux for this indication have thus far been
      favorable, the diagnosis of HIT in most cases was not based on definitive
      laboratory confirmation of heparin-dependent, platelet-activating antibodies.
      OBJECTIVES: To report thrombotic and major bleeding outcomes with fondaparinux in
      patients with a high likelihood of having acute HIT based on clinical features
      and a positive result in the confirmatory platelet serotonin-release assay (SRA),
      a sensitive and specific test for platelet-activating HIT antibodies.
      METHODS/PATIENTS: We reviewed consecutive eligible patients with SRA-positive HIT
      (mean peak serotonin release, 91% [normal, < 20%]; mean IgG-specific PF4/heparin
      enzyme immunoassay result, 2.53 optical density units [normal, < 0.45 units]) in
      one medical center over a 30-month period who received fondaparinux for
      anticoagulation during acute HIT (platelet count, < 150 * 10(9) L(-1)). Where
      available, plasma samples were used to measure thrombin-antithrombin (TAT)
      complex levels. RESULTS: Sixteen patients with SRA-positive HIT received
      fondaparinux: 14 surgical (11 after cardiac surgery; three after vascular
      surgery) and two medical (acute stroke). Fifty-six per cent of patients had HIT
      associated thrombosis at the time of diagnosis. No patient developed new,
      recurrent or progressive thrombosis; one patient developed a major bleed (calf
      hematoma). One patient judged to have irreversible tissue necrosis before
      receiving fondaparinux therapy ultimately required limb amputation. TAT complex
      levels were reduced within 24 h of starting fondaparinux, and 13 of 13 patients
      were successfully switched to warfarin. CONCLUSION: Fondaparinux shows promise
      for the treatment of patients with SRA-positive acute HIT.

PMID- 21883880
TI  - Differential contributions of monocyte- and platelet-derived microparticles
      towards thrombin generation and fibrin formation and stability.
AB  - BACKGROUND: Microparticles (MPs) are sub-micron vesicles shed by activated or
      apoptotic cells, including platelets and monocytes. Increased circulating MPs are
      associated with thrombosis; however, their role in thrombogenesis is poorly
      understood. OBJECTIVE: To determine how MPs promote thrombin generation and
      modulate fibrin density and stability. METHODS: Platelets and monocytes were
      isolated from healthy donors. Platelets were stimulated with calcium ionophore,
      thrombin receptor agonist peptide (TRAP) or TRAP/convulxin. Monocytes and human
      monocytic THP-1 cells were stimulated with lipopolysaccharide (LPS). MPs were
      isolated, washed by high-speed centrifugation and assessed using the following:
      transmission electron microscopy (TEM), Nanoparticle Tracking Analysis (NTA),
      flow cytometry, tissue factor (TF) activity, prothrombinase activity, thrombin
      generation, and clot formation, density and stability. RESULTS: MPs from
      monocytes (M-MPs) and platelets (PMPs) had similar shapes and diameters (100-300
      nm). M-MPs had TF activity (16.7 +/- 2.4 pm TF per 10(6) MP), supported
      prothrombinase activity and triggered shorter thrombin generation lag times than
      buffer controls (5.4 +/- 0.5 vs. 84.2 +/- 4.8 min, respectively). Compared with
      controls, M-MPs supported faster fibrin formation (0.24 +/- 0.24 vs. 76.7 +/-
      15.1 mOD min(-1) , respectively), 38% higher fibrin network density and higher
      clot stability (3.8-fold higher turbidity in the presence of tissue plasminogen
      activator). In contrast, PMPs did not have TF activity and supported 2.8-fold
      lower prothrombinase activity than M-MPs. PMPs supported contact-dependent
      thrombin generation, but did not independently increase fibrin network density or
      stability. Interestingly, PMPs increased rates of thrombin generation and fibrin
      formation (1.7- and 1.3-fold, respectively) when mixed with THP-1-derived MPs.
      CONCLUSION: MPs from platelets and monocytes differentially modulate clot
      formation, structure and stability, suggesting unique contributions to
      thrombosis.

PMID- 21883881
TI  - Fondaparinux in acute heparin-induced thrombocytopenia: a case series.

PMID- 21883882
TI  - The effects of cause of death classification on prognostic assessment of patients
      with pulmonary embolism.
AB  - BACKGROUND: Although previous studies have provided evidence that the majority of
      deaths following an acute pulmonary embolism (PE) directly relate to the PE, more
      recent registries and cohort studies suggest otherwise. METHODS: We assessed the
      cause of death during the first 30 days after the diagnosis of acute symptomatic
      PE in a consecutive series of patients. We also assessed the prognostic
      characteristics of the simplified Pulmonary Embolism Severity Index (sPESI) and
      cardiac troponin I (cTnI) obtained at the time of PE diagnosis. RESULTS: During
      the first 30 days after diagnosis, 127 of the 1291 patients died (9.8%; 95%
      confidence interval [CI], 8.2-11.5). Sixty patients (4.6%; 95% CI, 3.5-5.8) died
      from definite or possible PE, and 67 (5.2%; 95% CI, 4.0-6.4) died from other
      causes (cancer 25, infection 18, hemorrhage 7, heart failure 7, chronic
      obstructive pulmonary disease 5, renal failure 1, seizures 1, unknown 3). The
      sPESI predicted all-cause (odds ratio [OR], 5.97; 95% CI, 1.74-20.54; P < 0.01)
      and PE-associated mortality (OR, 8.79; 95% CI, 1.12-68.79; P = 0.04). cTnI only
      predicted PE-associated mortality (adjusted OR, 2.39; 95% CI, 1.25-4.57; P <
      0.01). For all-cause mortality, the sPESI low-risk strata had a negative
      predictive value of 98.8% (95% CI, 97.4-100) in comparison with 91.3% (95% CI,
      88.9-93.6) for the cTnI. CONCLUSIONS: Within the first 30 days after the
      diagnosis of acute symptomatic PE, death due to PE and death due to other causes
      occur in a similar proportion of patients. As cTnI only predicted PE-associated
      mortality, low-risk sPESI had a higher negative predictive value for all-cause
      mortality compared with cTnI.

PMID- 21883883
TI  - Muscle-directed gene therapy for hemophilia B with more efficient and less
      immunogenic AAV vectors.
AB  - BACKGROUND: Adeno-associated viral vector (AAV)-mediated and muscle-directed gene
      therapy is a safe and non-invasive approach to treatment of hemophilia B and
      other genetic diseases. However, low efficiency of transduction, inhibitor
      formation and high prevalence of pre-existing immunity to the AAV capsid in
      humans remain as main challenges for AAV2-based vectors using this strategy.
      Vectors packaged with AAV7, 8 and 9 serotypes have improved gene transfer
      efficiencies and may provide potential alternatives to overcome these problems.
      OBJECTIVE: To compare the long-term expression of canine factor IX (cFIX) levels
      and anti-cFIX antibody responses following intramuscular injection of vectors
      packaged with AAV1, 2, 5, 7, 8 and 9 capsid in immunocompetent hemophilia B mice.
      RESULTS: Highest expression was detected in mice injected with AAV2/8 vector (28%
      of normal), followed by AAV2/9 (15%) and AAV2/7 (10%). cFIX expression by AAV2/1
      only ranged from 0 to 5% of normal levels. High incidences of anti-cFIX inhibitor
      (IgG) were detected in mice injected with AAV2 and 2/5 vectors, followed by
      AAV2/1. None of the mice treated with AAV2/7, 2/8 and 2/9 developed inhibitors or
      capsid T cells. CONCLUSIONS: AAV7, 8 and 9 are more efficient and safer vectors
      for muscle-directed gene therapy with high levels of transgene expression and
      absence of inhibitor formation. The absence of antibody response to transgene by
      AAV7, 8 and 9 is independent of vector dose but may be due to the fact that these
      three serotypes are associated with high level distribution to, and transduction
      of, hepatocytes following i.m. injection.

PMID- 21883884
TI  - The use of a single von Willebrand factor-containing, plasma-derived FVIII
      product in hemophilia A immune tolerance induction: the US experience.
AB  - BACKGROUND: Inhibitors are a serious complication for patients with severe
      hemophilia A. Immune tolerance induction (ITI) is the primary method for
      eradicating these inhibitors. The role of type of concentrate and in particular
      the use of von Willebrand factor-containing, plasma-derived factor VIII (VWF/pd
      FVIII) concentrate in primary or rescue ITI remains unclear. OBJECTIVES: To
      report retrospective collection of data on the use of a single VWF/pd-FVIII
      concentrate in primary and rescue ITI. METHODS: Retrospective chart review of
      hemophilia A inhibitor patients at 11 US institutions who received VWF/pd-FVIII
      concentrate in primary or rescue ITI. RESULTS: Primary ITI was carried out in
      eight inhibitor patients with a 75% complete and partial success. Secondary ITI
      was carried out in 25 inhibitor patients, with 52% attaining complete or partial
      success. CONCLUSIONS: This report represents the largest group of primarily
      pediatric, high-titer inhibitor patients treated with a single VWF/pd-FVIII
      concentrate. It adds retrospective data to the use of VWF-containing plasma
      derived factor VIII concentrate in primary and rescue ITI, particularly in those
      patients with characteristics of poor response to ITI.

PMID- 21883885
TI  - A functional variant in the thrombospondin-1 gene and the risk of small for
      gestational age infants.
AB  - INTRODUCTION: Thrombospondin-1 (TSP-1) is a prothrombotic and anti-angiogenic
      glycoprotein expressed in the placenta. A functional single nucleotide
      polymorphism in the TSP-1 gene (TSP-1 A2210G) is a risk factor for familial
      premature myocardial infarction. Small for gestational age (SGA) infants are at
      increased risk of coronary artery disease in adult life and common genetic
      factors may underlie both conditions. We investigated the association of TSP-1
      A2210G in SGA infants and their parents. METHOD: The 3234 nulliparous pregnant
      women, their partners and babies were recruited in Adelaide and Auckland to a
      prospective multicenter cohort study. Amongst 2123 Caucasian women, 216 (10.2%)
      delivered an SGA infant, defined as birth weight < 10th customized centile
      adjusted for maternal height, weight, parity and ethnicity, as well as
      gestational age at delivery and infant sex. Uncomplicated pregnancies served as
      controls (n = 1185). DNA extracted from peripheral/cord blood or buccal swabs was
      genotyped using Sequenom MassARRAY. Multivariable logistic regression was used to
      compare the odds of SGA between the genotype groups adjusting for potential
      confounders. RESULTS: Paternal (adjOR, 1.4; 95% CI 1.0-2.0) and neonatal (adjOR,
      1.8; 95% CI, 1.1-2.7) TSP-1 A2210G associates with SGA. The maternal polymorphism
      approaches significance for an association with SGA (adjOR, 1.3; 95% CI, 0.9
      1.9). Maternal TSP-1 A2210G associates with a reduced maternal birth weight
      adjusted for gestational age at delivery (P = 0.03). CONCLUSION: The TSP-1 A2210G
      polymorphism, which is a risk factor for myocardial infarction, is associated
      with SGA pregnancies, suggesting that this polymorphism may associate with the
      risk of vascular disorders across the life course.

PMID- 21883886
TI  - TAFIa inhibiting nanobodies as profibrinolytic tools and discovery of a new TAFIa
      conformation.
AB  - BACKGROUND: Because activated thrombin activatable fibrinolysis inhibitor (TAFIa)
      has very powerful antifibrinolytic properties, co-administration of t-PA and a
      TAFIa inhibitor enhances t-PA treatment. OBJECTIVE: We aimed to generate
      nanobodies specifically inhibiting the TAFIa activity and to test their effect on
      t-PA induced clot lysis. RESULTS: Five nanobodies, raised towards an activated
      more stable TAFIa mutant (TAFIa A(147) -C(305) -I(325) -I(329) -Y(333) -Q(335) ),
      are described. These nanobodies inhibit specifically TAFIa activity, resulting in
      an inhibition of up to 99% at a 16-fold molar excess of nanobody over TAFIa,
      IC(50) 's range between 0.38- and > 16-fold molar excess. In vitro clot lysis
      experiments in the absence of thrombomodulin (TM) demonstrate that the nanobodies
      exhibit profibrinolytic effects. However, in the presence of TM, one nanobody
      exhibits an antifibrinolytic effect whereas the other nanobodies show a slight
      antifibrinolytic effect at low concentrations and a pronounced profibrinolytic
      effect at higher concentrations. This biphasic pattern was highly dependent on TM
      and t-PA concentration. The nanobodies were found to bind in the active-site
      region of TAFIa and their time-dependent differential binding behavior during
      TAFIa inactivation revealed the occurrence of a yet unknown intermediate
      conformational transition. CONCLUSION: These nanobodies are very potent TAFIa
      inhibitors and constitute useful tools to accelerate fibrinolysis. Our data also
      demonstrate that the profibrinolytic effect of TAFIa inhibition may be reversed
      by the presence of TM. The identification of a new conformational transition
      provides new insights into the conformational inactivation of the unstable TAFIa.

PMID- 21883887
TI  - Altered distribution of interstitial cells and innervation in the rat urinary
      bladder following spinal cord injury.
AB  - Changes in the distribution of interstitial cells (IC) are reportedly associated
      with dysfunctional bladder. This study investigated whether spinal cord injury
      (SCI) resulted in changes to IC subpopulations (vimentin-positive with the
      ultrastructural profile of IC), smooth muscle and nerves within the bladder wall
      and correlated cellular remodelling with functional properties. Bladders from SCI
      (T8/9 transection) and sham-operated rats 5 weeks post-injury were used for ex
      vivo pressure-volume experiments or processed for morphological analysis with
      transmission electron microscopy (TEM) and light/confocal microscopy. Pressure
      volume relationships revealed low-pressure, hypercompliance in SCI bladders
      indicative of decompensation. Extensive networks of vimentin-positive IC were
      typical in sham lamina propria and detrusor but were markedly reduced post-SCI;
      semi-quantitative analysis showed significant reduction. Nerves labelled with
      anti-neurofilament and anti-vAChT were notably decreased post-SCI. TEM revealed
      lamina propria IC and detrusor IC which formed close synaptic-like contacts with
      vesicle-containing nerve varicosities in shams. Lamina propria and detrusor IC
      were ultrastructurally damaged post-SCI with retracted/lost cell processes and
      were adjacent to areas of cellular debris and neuronal degradation. Smooth muscle
      hypertrophy was common to SCI tissues. In conclusion, IC populations in bladder
      wall were decreased 5 weeks post-SCI, accompanied with reduced innervation,
      smooth muscle hypertrophy and increased compliance. These novel findings indicate
      that bladder wall remodelling post-SCI affects the integrity of interactions
      between smooth muscle, nerves and IC, with compromised IC populations.
      Correlation between IC reduction and a hypercompliant phenotype suggests that
      disruption to bladder IC contribute to pathophysiological processes underpinning
      the dysfunctional SCI bladder.

PMID- 21883888
TI  - Cardiomyocytes derived from human embryonic and induced pluripotent stem cells:
      comparative ultrastructure.
AB  - Induced pluripotent stem cells (iPSC) are generated from fully differentiated
      somatic cells that were reprogrammed into a pluripotent state. Human iPSC which
      can be obtained from various types of somatic cells such as fibroblasts or
      keratinocytes can differentiate into cardiomyocytes (iPSC-CM), which exhibit
      cardiac-like transmembrane action potentials, intracellular Ca(2+) transients and
      contractions. While major features of the excitation-contraction coupling of iPSC
      CM have been well-described, very little is known on the ultrastructure of these
      cardiomyocytes. The ultrastructural features of 31-day-old (post-plating) iPSC-CM
      generated from human hair follicle keratinocytes (HFKT-iPSC-CM) were analysed by
      electron microscopy, and compared with those of human embryonic stem-cell-derived
      cardiomyocytes (hESC-CM). The comparison showed that cardiomyocytes from the two
      sources share similar proprieties. Specifically, HFKT-iPSC-CM and hESC-CM,
      displayed ultrastructural features of early and immature phenotype: myofibrils
      with sarcomeric pattern, large glycogen deposits, lipid droplets, long and
      slender mitochondria, free ribosomes, rough endoplasmic reticulum, sarcoplasmic
      reticulum and caveolae. Noteworthy, the SR is less developed in HFKT-iPSC-CM. We
      also found in both cell types: (1) 'Ca(2+)-release units', which connect the
      peripheral sarcoplasmic reticulum with plasmalemma; and (2) intercellular
      junctions, which mimic intercalated disks (desmosomes and fascia adherens). In
      conclusion, iPSC and hESC differentiate into cardiomyocytes of comparable
      ultrastructure, thus supporting the notion that iPSC offer a viable option for an
      autologous cell source for cardiac regenerative therapy.

PMID- 21883889
TI  - Selection of disease-specific biomarkers by integrating inflammatory mediators
      with clinical informatics in AECOPD patients: a preliminary study.
AB  - Systemic inflammation is a major factor influencing the outcome and quality of
      patient with chronic obstructive pulmonary disease (COPD) and acute exacerbations
      (AECOPD). Because of the inflammatory complexity, a great challenge is still
      confronted to optimize the identification and validation of disease-specific
      biomarkers. This study aimed at developing a new protocol of specific biomarker
      evaluation by integrating proteomic profiles of inflammatory mediators with
      clinical informatics in AECOPD patients, understand better their function and
      signal networks. Plasma samples were collected from healthy non-smokers or
      patients with stable COPD (sCOPD) or AECOPD on days 1 and 3 of the admission and
      discharging day (day 7-10). Forty chemokines were measured using a chemokine
      multiplex antibody array. Clinical informatics was achieved by a Digital
      Evaluation Score System (DESS) for assessing severity of patients. Chemokine data
      was compared among different groups and its correlation with DESS scores was
      performed by SPSS software. Of 40 chemokines, 30 showed significant difference
      between sCOPD patients and healthy controls, 16 between AECOPD patients and
      controls and 13 between AECOPD patients and both sCOPD and controls, including
      BTC, IL-9, IL-18Bpa, CCL22,CCL23, CCL25, CCL28, CTACK, LIGHT, MSPa, MCP-3, MCP-4
      and OPN. Of them, some had significant correlation with DESS scores. There is a
      disease-specific profile of inflammatory mediators in COPD and AECOPD patients
      which may have a potential diagnostics together with clinical informatics of
      patients. Our preliminary study suggested that integration of proteomics with
      clinical informatics can be a new way to validate and optimize disease-special
      biomarkers.

PMID- 21883890
TI  - Bone marrow mesenchymal stem cells can differentiate and assume corneal
      keratocyte phenotype.
AB  - It remains elusive as to what bone marrow (BM) cell types infiltrate into injured
      and/or diseased tissues and subsequently differentiate to assume the phenotype of
      residential cells, for example, neurons, cardiac myocytes, keratocytes, etc., to
      repair damaged tissue. Here, we examined the possibility of whether BM cell
      invasion via circulation into uninjured and injured corneas could assume a
      keratocyte phenotype, using chimeric mice generated by transplantation of
      enhanced green fluorescent protein (EGFP)(+) BM cells into keratocan null (Kera(
      /-)) and lumican null (Lum(-/-)) mice. EGFP(+) BM cells assumed dendritic cell
      morphology, but failed to synthesize corneal-specific keratan sulfate
      proteoglycans, that is KS-lumican and KS-keratocan. In contrast, some EGFP(+) BM
      cells introduced by intrastromal transplantation assumed keratocyte phenotypes.
      Furthermore, BM cells were isolated from Kera-Cre/ZEG mice, a double transgenic
      mouse line in which cells expressing keratocan become EGFP(+) due to the
      synthesis of Cre driven by keratocan promoter. Three days after corneal and
      conjunctival transplantations of such BM cells into Kera(-/-) mice, green
      keratocan positive cells were found in the cornea, but not in conjunctiva. It is
      worthy to note that transplanted BM cells were rejected in 4 weeks. MSC isolated
      from BM were used to examine if BM mesenchymal stem cells (BM-MSC) could assume
      keratocyte phenotype. When BM-MSC were intrastromal-transplanted into Kera(-/-)
      mice, they survived in the cornea without any immune and inflammatory responses
      and expressed keratocan in Kera(-/-) mice. These observations suggest that
      corneal intrastromal transplantation of BM-MSC may be an effective treatment
      regimen for corneal diseases involving dysfunction of keratocytes.

PMID- 21883879
TI  - The timing, extent, progression and regression of deep vein thrombosis in
      immobile stroke patients: observational data from the CLOTS multicenter
      randomized trials.
AB  - BACKGROUND: Deep vein thrombosis (DVT) is an important complication of stroke,
      but the evidence to support commonly used prophylactic strategies is conflicting.
      OBJECTIVES: To describe the incidence, extent, associated clinical features and
      evolution of DVT after stroke. PATIENTS/METHODS: The CLOTS trials 1 and 2
      together randomized 5632 immobile stroke patients in 135 hospitals in nine
      countries. We screened patients for asymptomatic DVT with compression duplex
      ultrasound (CDU) at about 7-10 days and again at about 25-30 days after
      enrollment. RESULTS: Six hundred and forty-one (11.4%) of 5632 patients had DVT
      detected on the first CDU scan at a median of 8 days (interquartile range [IQR] 7
      10 days) after enrollment, and an additional 176 (3.1%) had a DVT on the second
      CDU scan at a median of 28 days (IQR 26-30 days). Of the 817 with DVTs, 289 (35%)
      were symptomatic and 39 (5%) had pulmonary embolism (PE) confirmed by imaging.
      Six hundred and seventy-six (83%) were unilateral, 141 (17%) were bilateral, 322
      (39%) were limited to calf veins, 172 (21%) were popliteal, and 323 (40%) were
      femoral. Among the 542 patients with DVT and a weak leg, the DVT affected the
      weaker leg in 396 (73%), the stronger leg in 59 (11%), and was bilateral in 87
      (16%). Among the 318 patients with a DVT detected on the first CDU scan who had a
      second scan, the DVT regressed in 148 (47%), stayed the same in 140 (44%), and
      progressed in only 30 (9%). CONCLUSIONS: Although most DVTs develop within the
      first week, some develop later, and some early DVTs progress. Any prophylaxis
      needs to be started early but ideally continued for at least 4 weeks.

PMID- 21883891
TI  - aV integrins and TGF-beta-induced EMT: a circle of regulation.
AB  - Transforming growth factor-beta (TGF-beta) has roles in embryonic development,
      the prevention of inappropriate inflammation and tumour suppression. However, TGF
      beta signalling also regulates pathological epithelial-to-mesenchymal transition
      (EMT), inducing or progressing a number of diseases ranging from inflammatory
      disorders, to fibrosis and cancer. However, TGF-beta signalling does not proceed
      linearly but rather induces a complex network of cascades that mutually influence
      each other and cross-talk with other pathways to successfully induce EMT.
      Particularly, there is substantial evidence for cross-talk between alphaV
      integrins and TGF-beta during EMT, and anti-integrin therapeutics are under
      development as treatments for TGF-beta-related disorders. However, TGF-beta's
      complex signalling network makes the development of therapeutics to block TGF
      beta-mediated pathology challenging. Moreover, despite our current understanding
      of integrins and TGF-beta function during EMT, the precise mechanism of their
      role during physiological versus pathological EMT is not fully understood. This
      review focuses on the circle of regulation between alphaV integrin and TGF-beta
      signalling during TGF-beta induced EMT, which pose as a significant driver to
      many known TGF-beta-mediated disorders.

PMID- 21883893
TI  - Lysophosphatidylcholine inhibits membrane-associated SNARE complex disassembly.
AB  - In cells, N-ethylmaleimide-sensitive factor (NSF) attachment protein receptors
      called SNAREs are involved in membrane fusion. In neurons, for example, target
      membrane proteins SNAP-25 and syntaxin called t-SNAREs present at the pre
      synaptic membrane, and a synaptic vesicle-associated membrane protein (VAMP) or v
      SNARE, is part of the conserved protein complex involved in neurotransmission.
      Cholesterol and LPC (L-alpha-lysophosphatidylcholine) are known to contribute to
      the negative and positive curvature respectively of membranes. In this study,
      using purified recombinant neuronal membrane-associated SNAREs, we demonstrate
      for the first time that membrane-curvature-influencing lipids profoundly
      influence SNARE complex disassembly. Exposure of cholesterol-associated t-SNARE
      and v-SNARE liposome mixtures to NSF-ATP results in dissociated vesicles. In
      contrast, exposure of LPC-associated t-SNARE and v-SNARE liposome mixtures to NSF
      ATP, results in inhibition of t-/v-SNARE disassembly and the consequent
      accumulation of clustered vesicles. Similarly, exposure of isolated rat brain
      slices and pancreas to cholesterol or LPC, also demonstrates LPC-induced
      inhibition of SNARE complex disassembly. Earlier studies demonstrate a strong
      correlation between altered plasma LPC levels and cancer. The altered plasma LPC
      levels observed in various cancers may in part contribute to defects in SNARE
      assembly-disassembly and membrane fusion, consequently affecting protein
      maturation and secretion in cancer cells.

PMID- 21883892
TI  - Trichostatin A induces 5-lipoxygenase promoter activity and mRNA expression via
      inhibition of histone deacetylase 2 and 3.
AB  - The 5-lipoxygenase (5-LO) is the key enzyme in the formation of leukotrienes. We
      have previously shown that the histone deacetylase (HDAC) inhibitor trichostatin
      A (TSA) activates 5-LO transcription via recruitment of Sp1, Sp3 and RNA
      polymerase II to the proximal promoter. To identify the HDACs involved in the
      regulation of 5-LO promoter activity isoform-specific HDAC inhibitors were
      applied. 5-LO promoter activity and mRNA expression were up-regulated by the
      class I HDAC inhibitors apicidin and MS-275 but not by class II inhibitors.
      Knockdown of HDAC 1, 2 and 3 revealed that HDAC2 and HDAC3 but not HDAC1 is
      involved in the up-regulation of 5-LO mRNA expression. To analyse the chromatin
      modifications at the 5-LO promoter associated with HDAC inhibition, the time
      course of 5-LO mRNA induction by trichostatin A was investigated and the
      concomitant changes in histone modifications at the 5-LO promoter in HL-60, U937
      and Mono Mac6 cells were determined. Chromatin immunoprecipitation analysis
      revealed that trichostatin A increases acetylation of histones H3 and H4 at the 5
      LO core promoter in HL-60 and U937 cells whereas no significant changes were
      observed in Mono Mac6 cells. The appearance of H3 and H4 acetylation preceded the
      5-LO mRNA induction whereas in all three cell lines, induction of 5-LO mRNA
      expression correlated with histone H3 lysine 4 trimethylation (H3K4me3), a marker
      for transcriptional activity of gene promoters.

PMID- 21883894
TI  - Endocytosis and intracellular processing of platelet microparticles by brain
      endothelial cells.
AB  - Platelet-derived microparticles (PMP) bind and modify the phenotype of many cell
      types including endothelial cells. Recently, we showed that PMP were internalized
      by human brain endothelial cells (HBEC). Here we intend to better characterize
      the internalization mechanisms of PMP and their intracellular fate. Confocal
      microscopy analysis of PKH67-labelled PMP distribution in HBEC showed PMP in
      early endosome antigen 1 positive endosomes and in LysoTracker-labelled
      lysosomes, confirming a role for endocytosis in PMP internalization. No fusion of
      calcein-loaded PMP with HBEC membranes was observed. Quantification of PMP
      endocytosis using flow cytometry revealed that it was partially inhibited by
      trypsin digestion of PMP surface proteins and by extracellular Ca(2+) chelation
      by EDTA, suggesting a partial role for receptor-mediated endocytosis in PMP
      uptake. This endocytosis was independent of endothelial receptors such as
      intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 and was
      not increased by tumour necrosis factor stimulation of HBEC. Platelet-derived
      microparticle internalization was dramatically increased in the presence of
      decomplemented serum, suggesting a role for PMP opsonin-dependent phagocytosis.
      Platelet-derived microparticle uptake was greatly diminished by treatment of HBEC
      with cytochalasin D, an inhibitor of microfilament formation required for both
      phagocytosis and macropinocytosis, with methyl-beta-cyclodextrin that depletes
      membrane cholesterol needed for macropinocytosis and with amiloride that inhibits
      the Na(+)/H(+) exchanger involved in macropinocytosis. In conclusion, PMP are
      taken up by active endocytosis in HBEC, involving mechanisms consistent with both
      phagocytosis and macropinocytosis. These findings identify new processes by which
      PMP could modify endothelial cell phenotype and functions.

PMID- 21883895
TI  - Identification of new cancer biomarkers based on aberrant mucin glycoforms by in
      situ proximity ligation.
AB  - Mucin glycoproteins are major secreted or membrane-bound molecules that, in
      cancer, show modifications in both the mucin proteins expression and in the O
      glycosylation profile, generating some of the most relevant tumour markers in
      clinical use for decades. Thus far, the identification of these biomarkers has
      been based on the detection of either the protein or the O-glycan modifications.
      We therefore aimed to identify the combined mucin and O-glycan features, that is,
      specific glycoforms, in an attempt to increase specificity of these cancer
      biomarkers. Using in situ proximity ligation assays (PLA) based on existing
      monoclonal antibodies directed to MUC1, MUC2, MUC5AC and MUC6 mucins and to
      cancer-associated carbohydrate antigens Tn, Sialyl-Tn (STn), T, Sialyl-Le(a)
      (SLe(a)) and Sialyl-Le(x) (SLe(x)) we screened a series of 28 mucinous
      adenocarcinomas from different locations (stomach, ampulla of Vater, colon, lung,
      breast and ovary) to detect specific mucin glycoforms. We detected
      Tn/STn/SLe(a)/SLe(x)-MUC1 and STn/SLe(a)/SLe(x)-MUC2 glycoforms in >=50% of the
      cases, with a variable distribution among organs. Some new glycoforms-T/SLe(a)
      MUC2, STn/T/SLe(a) SLe(x)-MUC5AC and STn/T/SLe(a)/SLe(x)-MUC6-were identified for
      the first time in the present study in a variable percentage of cases from
      different organs. In conclusion, application of the PLA technique allowed
      sensitive detection of specific aberrant mucin glycoforms in cancer, increasing
      specificity to the use of antibodies either to the mucin protein backbone or to
      the O-glycan haptens alone.

PMID- 21883896
TI  - Everolimus is an active agent in medullary thyroid cancer: a clinical and in
      vitro study.
AB  - Everolimus, an mTOR inhibitor, which has been demonstrated to induce anti-tumour
      effects in different types of neuroendocrine tumours, has never been evaluated in
      patients with medullary thyroid cancer (MTC). The aim of this study was to
      evaluate the in vitro and in vivo effects of everolimus in combination with
      octreotide in MTC. Two patients with progressive metastatic MTC and high
      calcitonin levels were treated with everolimus 5-10 mg/day. Both patients were
      under treatment with octreotide LAR at the study entry. An in vitro study was
      also performed to assess everolimus effects on MTC cell lines (TT and MZ-CRC-1
      cells). A tumour response was observed in both patients. Serum calcitonin
      decreased by 86% in patient 1 and by 42% in patient 2. In TT and MZ-CRC-1 cells,
      everolimus induced a significant dose-dependent inhibition in cell proliferation.
      This effect seems to be related to a cell cycle arrest in G(0) /G(1)  phase in
      both cell lines and to the induction of cellular senescence in TT cells.
      Everolimus in combination with octreotide may be active as anti-tumour therapy in
      patients with progressive metastatic MTC, suggesting to further evaluate this
      agent in MTC patients in a large prospective study.

PMID- 21883897
TI  - Analysis of microdissected neurons by 18O mass spectrometry reveals altered
      protein expression in Alzheimer's disease.
AB  - It is evident that the symptoms of Alzheimer's disease (AD) are derived from
      severe neuronal damage, and especially pyramidal neurons in the hippocampus are
      affected pathologically. Here, we analysed the proteome of hippocampal neurons,
      isolated from post-mortem brains by laser capture microdissection. By using (18)O
      labelling and mass spectrometry, the relative expression levels of 150 proteins
      in AD and controls were estimated. Many of the identified proteins are involved
      in transcription and nucleotide binding, glycolysis, heat-shock response,
      microtubule stabilization, axonal transport or inflammation. The proteins showing
      the most altered expression in AD were selected for immunohistochemical analysis.
      These analyses confirmed the altered expression levels, and showed in many AD
      cases a pathological pattern. For comparison, we also analysed hippocampal
      sections by Western blot. The expression levels found by this method showed poor
      correlation with the neuron-specific analysis. Hence, we conclude that cell
      specific proteome analysis reveals differences in the proteome that cannot be
      detected by bulk analysis.

PMID- 21883898
TI  - Basement membrane collagen type IV expression by human mesenchymal stem cells
      during adipogenic differentiation.
AB  - During adipogenic differentiation human mesenchymal stem cells (hMSC) produce
      collagen type IV. In immunofluorescence staining differentiating hMSCs started to
      express collagen type IV when Oil Red O-positive fat droplets appeared
      intracellularly. Quantitative real time-polymerase chain reaction confirmed
      progressive increase of collagen type IV alpha1 and alpha2 mRNA levels over time,
      18.6- and 12.2-fold by day 28, respectively, whereas the copy numbers of alpha3
      alpha6 mRNAs remained rather stable and low. Type IV collagen was in confocal
      laser scanning microscopy seen around adipocytes, where also laminins and nidogen
      were found, suggesting pericellular deposition of all key components of the fully
      developed basement membrane. Immunofluorescence staining of matrix
      metalloproteinase-2 (MMP-2, 72 kD type IV collagenase, gelatinase A) and MMP-9
      (92 kD type IV collagenase, gelatinase B) disclosed only faint staining of MSCs,
      but MMP-9 was strongly induced during adipogenesis, whereas MSC supernatants
      disclosed in zymography pro-MMP-2 and faint pro-MMP-9 bands, which increased over
      time, with partial conversion of pro-MMP-2 to its active 62 kD form.
      Differentiation was associated with increasing membrane type 1-MMP/MMP-14 and
      tissue inhibitor of metalloproteinase-2 (TIMP-2) staining, which may enable
      participation of type IV collagenases in basement membrane remodelling via
      ternary MT1-MMP/TIMP-2/MMP-2 or -9 complexes, focalizing the fully active enzyme
      to the cell surface. MMP-9, which increased more in immunofluorescence staining,
      was perhaps preferentially bound to cell surface and/or remodelling adipocyte
      basement membrane. These results suggest that upon MSC-adipocyte differentiation
      collagen type IV synthesis and remodelling become necessary when intracellular
      accumulation of fat necessitates a dynamically supporting and instructive, partly
      denatured adipogenic pericellular type IV collagen scaffold.

PMID- 21883899
TI  - A retrospective evaluation of iatrogenic dental root damage with predrilled vs
      drill-free bone anchor screws for intermaxillary fixation.
AB  - AIMS: The aim of this study was to retrospectively evaluate iatrogenic dental
      root damage, caused by two different techniques that utilized bone anchor screws,
      for intermaxillary fixation (IMF) in orofacial trauma. MATERIALS AND METHODS: The
      techniques used included either predrilled or drill-free bone anchor screws. A
      total of 123 patients who required IMF were evaluated (97 men and 26 women).
      Sixty-four patients were treated in the predrilled group, and 59 patients were
      treated in the drill-free group. The data were collected over an 8-year period
      and were analyzed using crosstabs and Fisher's exact test. RESULTS: Injuries to
      dental roots were found only in the predrilled group. Twenty-nine patients
      (45.3%) were injured at the time of surgery. One year after surgery, 10 patients
      (15.6%) had permanently injured dental roots. There was a significant difference
      in injury rates between the predrilled and drill-free groups 1 year after surgery
      (P < 0.001). CONCLUSION: There is an increased potential risk of iatrogenic
      injury and permanent damage to the dental roots when a technique that involves
      predrilled holes for bone anchor screws is used.

PMID- 21883900
TI  - Successful organ donation from brain dead donors in a Chinese organ
      transplantation center.
AB  - Solid organ transplantation is an effective treatment for patients with end-stage
      organ failure. Donation after brain death (DBD) is a means of addressing the
      inadequate supply of acceptable donor organs but has only gradually begun to be
      accepted in mainland China. A major barrier has been the absence of brain death
      and organ transplant legislation. This paper describes our initial experience
      with organ transplantation using organs from brain dead donors and discusses
      strategies for encouraging organ transplantation and brain death legislation in
      China. Six patients underwent renal transplantation and two patients underwent
      liver transplantation with organs procured from three brain dead donors at the
      Organ Transplantation Center, the 181st Hospital. All patients are alive with
      excellent graft function. DBD is an important means of increasing the number of
      organs available for transplantation and its widespread implementation in China
      should be encouraged. Brain death and organ transplantation legislation is
      necessary to ensure the rights and obligations of donors, recipients and medical
      institutions.

PMID- 21883901
TI  - Systematic review: kidney transplantation compared with dialysis in clinically
      relevant outcomes.
AB  - Individual studies indicate that kidney transplantation is associated with lower
      mortality and improved quality of life compared with chronic dialysis treatment.
      We did a systematic review to summarize the benefits of transplantation, aiming
      to identify characteristics associated with especially large or small relative
      benefit. Results were not pooled because of expected diversity inherent to
      observational studies. Risk of bias was assessed using the Downs and Black
      checklist and items related to time-to-event analysis techniques. MEDLINE and
      EMBASE were searched up to February 2010. Cohort studies comparing adult chronic
      dialysis patients with kidney transplantation recipients for clinical outcomes
      were selected. We identified 110 eligible studies with a total of 1 922 300
      participants. Most studies found significantly lower mortality associated with
      transplantation, and the relative magnitude of the benefit seemed to increase
      over time (p < 0.001). Most studies also found that the risk of cardiovascular
      events was significantly reduced among transplant recipients. Quality of life was
      significantly and substantially better among transplant recipients. Despite
      increases in the age and comorbidity of contemporary transplant recipients, the
      relative benefits of transplantation seem to be increasing over time. These
      findings validate current attempts to increase the number of people worldwide
      that benefit from kidney transplantation.

PMID- 21883902
TI  - Long-term impact of subclinical inflammation diagnosed by protocol biopsy one
      year after renal transplantation.
AB  - The long-term impact of subclinical acute rejection (SCAR) on renal graft
      function remains poorly understood. Furthermore, the interpretation of borderline
      lesions is difficult and their incidence is variable. The aim of this study was
      to analyze the characteristics of subclinical inflammation (SCI) in protocol
      biopsies performed 1-year after renal transplantation. SCI was defined as the
      presence of borderline lesions or SCAR according to the Banff 2005
      classification. The patients included were a subpopulation of the CONCEPT study
      in which patients were randomized 3 months after transplantation to receive
      either sirolimus (SRL) or cyclosporine A (CsA) in combination with mycophenolate
      mofetil. At 1 year, we observed SCI in 37 of the 121 patients observed with an
      evaluable biopsy. The incidence was more frequent in the SRL group (SRL 45.2% vs.
      CsA 15.3%). At 30 months , SCI was associated with a significantly lower level of
      estimated glomerular filtration rate (mean MDRD 50.8 [+/-13.3] vs. 57.7 [+/-16.3]
      mL/min/1.73 m(2) , p = 0.035). In conclusion, SCI at 1-year posttransplantation
      is associated with worsening renal function and is more frequent in SRL-treated
      patients. Therefore, evaluation of SCI may be a valuable tool to allow the
      optimization of immunosuppressive regimens.

PMID- 21883904
TI  - Reverse chimerism: stem cells going the other way.

PMID- 21883903
TI  - Mobilization of host stem cells enables long-term liver transplant acceptance in
      a strongly rejecting rat strain combination.
AB  - Careful examination of liver, kidney and heart transplants in human recipients
      has revealed small numbers of host bone marrow derived stem cells in the graft.
      If the limited recipient repopulation of a donor graft that is currently observed
      could be facilitated, it is possible that conversion to a predominantly host
      phenotype would permit long-term graft function without immunosuppression. We
      proposed to "engineer" repopulation after transplant in a strain combination
      (dark agouti [DA] to Lewis green fluorescent protein+[LEW GFP+]) which rejects
      liver grafts strongly, a model that more closely resembles the situation in
      humans. Treatment on days 0, 1, 2, 3 and 7 after transplantation with low-dose
      (0.1 mg/kg) tacrolimus (T) designed to blunt rejection combined with plerixafor
      (P) to mobilize host stem cells resulted in greater than 180 days graft survival
      with extensive albeit spotty conversion of a small (50%) DA graft to the
      recipient LEW GFP+ genotype. Subsequent skin grafting revealed donor-specific
      graft prolongation. The T plus P treatment resulted in higher levels of Lin
      Thy1+CD34+CD133+ stem cells and Foxp3+ regulatory T cells in the blood and liver
      at day 7. Thus, pharmacological mobilization of host stem cells sustains liver
      allografts by two mechanisms: repopulation of injured donor cells and regulation
      of the immune response.

PMID- 21883906
TI  - Former smoking is a risk factor for chronic kidney disease after lung
      transplantation.
AB  - Chronic kidney disease (CKD) is a common complication after lung transplantation
      (LTx). Smoking is a risk factor for many diseases, including CKD. Smoking
      cessation for >6 months is required for LTx enlistment. However, the impact of
      smoking history on CKD development after LTx remains unclear. We investigated the
      effect of former smoking on CKD and mortality after LTx. CKD was based on
      glomerular filtration rate (GFR) ((125) I-iothalamate measurements). GFR was
      measured before and repeatedly after LTx. One hundred thirty-four patients never
      smoked and 192 patients previously smoked for a median of 17.5 pack years. At 5
      years after LTx, overall cumulative incidences of CKD-III, CKD-IV and death were
      68.5%, 16.3% and 34.6%, respectively. Compared to never smokers, former smokers
      had a higher risk for CKD-III (hazard ratio [HR] 95% confidence interval [95%CI]=
      1.69 [1.27-2.24]) and IV (HR = 1.90 [1.11-3.27]), but not for mortality (HR =
      0.99 [0.71-1.38]). Adjustment for potential confounders did not change results.
      Thus, despite cessation, smoking history remained a risk factor for CKD in LTx
      recipients. Considering the increasing acceptance for LTx of older recipients
      with lower baseline renal function and an extensive smoking history, our data
      suggest that the problem of post-LTx CKD may increase in the future.

PMID- 21883905
TI  - Sotrastaurin, a protein kinase C inhibitor, ameliorates ischemia and reperfusion
      injury in rat orthotopic liver transplantation.
AB  - Sotraustaurin (STN), a small molecule, targeted protein kinase C (PKC) inhibitor
      that prevents T-lymphocyte activation via a calcineurin-independent pathway, is
      currently being tested in Phase II renal and liver transplantation clinical
      trials. We have documented the key role of activated T cells in the inflammation
      cascade leading to liver ischemia/reperfusion injury (IRI). This study explores
      putative cytoprotective functions of STN in a clinically relevant rat model of
      hepatic cold ischemia followed by orthotopic liver transplantation (OLT). Livers
      from Sprague-Dawley rats were stored for 30 h at 4 degrees C in UW solution, and
      then transplanted to syngeneic recipients. STN treatment of liver
      donors/recipients or recipients only prolonged OLT survival to >90% (vs. 40% in
      controls), decreased hepatocellular damage and improved histological features of
      IRI. STN treatment decreased activation of T cells, and diminished
      macrophage/neutrophil accumulation in OLTs. These beneficial effects were
      accompanied by diminished apoptosis, NF-kappaB/ERK signaling, depressed
      proapoptotic cleaved caspase-3, yet upregulated antiapoptotic Bcl-2/Bcl-xl and
      hepatic cell proliferation. In vitro, STN decreased PKCtheta/IkappaBalpha
      activation and IL-2/IFN-gamma production in ConA-stimulated spleen T cells, and
      diminished TNF-alpha/IL-1beta in macrophage-T cell cocultures. This study
      documents positive effects of STN on liver IRI in OLT rat model that may
      translate as an additional benefit of STN in clinical liver transplantation.

PMID- 21883907
TI  - Elevated plasma long pentraxin-3 levels and primary graft dysfunction after lung
      transplantation for idiopathic pulmonary fibrosis.
AB  - Primary graft dysfunction (PGD) after lung transplantation may result from
      ischemia reperfusion injury (IRI). The innate immune response to IRI may be
      mediated by Toll-like receptor and IL-1-induced long pentraxin-3 (PTX3) release.
      We hypothesized that elevated PTX3 levels were associated with PGD. We performed
      a nested case control study of lung transplant recipients with idiopathic
      pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) from the
      Lung Transplant Outcomes Group cohort. PTX3 levels were measured pretransplant,
      and 6 and 24 h postreperfusion. Cases were subjects with grade 3 PGD within 72 h
      of transplantation and controls were those without grade 3 PGD. Generalized
      estimating equations and multivariable logistic regression were used for
      analysis. We selected 40 PGD cases and 79 non-PGD controls. Plasma PTX3 level was
      associated with PGD in IPF but not COPD recipients (p for interaction < 0.03).
      Among patients with IPF, PTX3 levels at 6 and 24 h were associated with PGD (OR =
      1.6, p = 0.02 at 6 h; OR = 1.4, p = 0.008 at 24 h). Elevated PTX3 levels were
      associated with the development of PGD after lung transplantation in IPF
      patients. Future studies evaluating the role of innate immune activation in IPF
      and PGD are warranted.

PMID- 21883908
TI  - Impact of MELD-based allocation on end-stage renal disease after liver
      transplantation.
AB  - The proportion of patients undergoing liver transplantation (LT), with
      concomitant renal dysfunction, markedly increased after allocation by the model
      for end-stage liver disease (MELD) score was introduced. We examined the
      incidence of subsequent post-LT end-stage renal disease (ESRD) before and after
      the policy was implemented. Data on all adult deceased donor LT recipients
      between April 27, 1995 and December 31, 2008 (n = 59 242), from the Scientific
      Registry of Transplant Recipients, were linked with Centers for Medicare &
      Medicaid Services' ESRD data. Cox regression was used to (i) compare pre-MELD and
      MELD eras with respect to post-LT ESRD incidence, (ii) determine the risk factors
      for post-LT ESRD and (iii) quantify the association between ESRD incidence and
      mortality. Crude rates of post-LT ESRD were 12.8 and 14.5 per 1000 patient-years
      in the pre-MELD and MELD eras, respectively. Covariate-adjusted post-LT ESRD risk
      was higher in the MELD era (hazard ratio [HR]= 1.15; p = 0.0049). African
      American race, hepatitis C, pre-LT diabetes, higher creatinine, lower albumin,
      lower bilirubin and sodium >141 mmol/L at LT were also significant predictors of
      post-LT ESRD. Post-LT ESRD was associated with higher post-LT mortality (HR =
      3.32; p < 0.0001). The risk of post-LT ESRD, a strong predictor of post-LT
      mortality, is 15% higher in the MELD era. This study identified potentially
      modifiable risk factors of post-LT ESRD. Early intervention and modification of
      these risk factors may reduce the burden of post-LT ESRD.

PMID- 21883909
TI  - Time trends in risk and risk determinants of non-Hodgkin lymphoma in solid organ
      transplant recipients.
AB  - Organ transplantation increases risk of non-Hodgkin lymphoma (NHL), but long-term
      risk and time trends have seldom been evaluated. Immunosuppressive drug load is
      an important risk determinant, but the details are unclear. We studied NHL risk
      in a nationwide Swedish cohort of 11 081 graft recipients transplanted 1970-2008.
      Relative risks (RRs) were estimated within the cohort and versus the general
      population by age, sex, follow-up time and calendar period. NHL risk was also
      assessed by cumulative and average doses of immunosuppressive treatments in a
      nested case-control design throughout 1997 using conditional logistic regression.
      We observed 153 NHL cases during 97 853 years of follow-up. Compared with the
      general population, NHL risk was eightfold increased (RR 7.9; 95% confidence
      interval [CI] 6.6-9.4), and increased risks persisted after >=15 years of follow
      up among kidney (6.1; 95% CI 3.5-10) and nonkidney recipients (44; 14-103). Among
      nonkidney recipients, NHL risk was lower in the 2000s compared with the 1990s
      (0.5; 95% CI 0.3-1.0; p = 0.04). A high average dose of antithymocyte
      immunoglobulin (ATG) conferred an eightfold increased risk of NHL (OR 8.5; 95% CI
      1.9-38). To conclude, posttransplant NHL risk decreased during the last decade
      among nonkidney recipients, possibly because of a more careful use of ATG, the
      introduction of new drugs, or both.

PMID- 21883910
TI  - Blood transfusions in organ transplant patients: mechanisms of sensitization and
      implications for prevention.
AB  - Sensitization by previous pregnancies or transplants is considered unavoidable,
      but it is transfusions given to these patients that leads most often to broad
      sensitization. Both leukocytes and red cells carry a significant HLA antigen
      load, and residual leukocytes and/or red cell HLA may explain why leukocyte
      reduced units are unable to prevent sensitization to any significant degree.
      Prevention of sensitization will require a more active effort to avoid blood
      transfusions, whenever possible. When transfusions are required, there is
      evidence that the use of HLA-matched blood or immunosuppression in selected
      situations may reduce sensitization, even in patients previously exposed to
      alloantigens. These additional measures are not logistically straightforward or
      devoid of risks and need to be confirmed by rigorous studies. However, remaining
      as passive observers when patients become broadly sensitized should no longer be
      considered an acceptable alternative for potential transplant recipients.

PMID- 21883911
TI  - A renal transplantation model for developing countries.
AB  - The estimated incidence of end-stage renal disease (ESRD) in Pakistan is 100 per
      million population. Paucity and high costs of renal replacement therapy allows
      only 10% to get dialysis and 4-5% transplants. Our center, a government
      organization, started a dialysis and transplant program in 1980s where all
      services were provided free of charge to all patients. It was based on the
      concept of community government partnership funded by both partners. The guiding
      principles were equity, transparency, accountability and development of all
      facilities under one roof. This partnership has sustained itself for 30 years
      with an annual budget of $25 million in 2009. Daily 600 patients are dialyzed and
      weekly 10-12 receive transplants. One- and 5-year graft survival of 3000
      transplants is 92% and 85%, respectively. The institute became a focus of
      transplantation in Pakistan and played a vital role in the campaign against
      transplant tourism and in promulgation of transplant law of 2007, and also helped
      to increase altruistic transplants in the country. This model emphasizes that in
      developing countries specialized centers in government sector are necessary for
      transplantation to progress and community support can make it available to the
      common man.

PMID- 21883912
TI  - Chronic illness management as an innovative pathway for enhancing long-term
      survival in transplantation.

PMID- 21883913
TI  - Pregnancy after transplantation: milestones and assessments of risk.

PMID- 21883914
TI  - Portal vein thrombosis is a potentially preventable complication in clinical
      islet transplantation.
AB  - Percutaneous transhepatic portal access avoids surgery but is rarely associated
      with bleeding or portal venous thrombosis (PVT). We herein report our large,
      single-center experience of percutaneous islet implantation and evaluate risk
      factors of PVT and graft function. Prospective data were collected on 268
      intraportal islet transplants (122 subjects). A portal venous Doppler ultrasound
      was obtained on Days 1 and 7 posttransplant. Therapeutic heparinization, complete
      ablation of the portal catheter tract with Avitene paste and limiting packed cell
      volume (PCV) to <5 mL completely prevented any portal thrombosis in the most
      recent 101 islet transplant procedures over the past 5 years. In the previous
      cumulative experience, partial thrombosis did not affect islet function. Standard
      liver volume correlated negatively (r =-0.257, p < 0.001) and PCV correlated
      positively with portal pressure rise (r = 0.463, p < 0.001). Overall, partial
      portal thrombosis occurred after 10 procedures (overall incidence 3.7%, most
      recent 101 patient incidence 0%). There were no cases of complete thrombosis and
      no patient developed sequelae of portal hypertension. In conclusion, portal
      thrombosis is a preventable complication in clinical islet transplantation,
      provided therapeutic anticoagulation is maintained and PCV is limited to <5 mL.

PMID- 21883915
TI  - Specificity of histological markers of long-term CNI nephrotoxicity in kidney
      transplant recipients under low-dose cyclosporine therapy.
AB  - The specificity of chronic histological lesions induced by calcineurin inhibitors
      (CNI) is often questioned, but few studies have directly compared long-term
      lesions in renal-transplant patients who received this treatment and those who
      did not. We therefore conducted a retrospective study of 141 kidney-transplant
      recipients treated with (n = 48) or without (n = 93) cyclosporine (CsA) to
      compare the histological lesions observed at 3-month, 24-month and 10-year
      protocol biopsies. All of the chronic elementary lesions (glomerulosclerosis,
      interstitial fibrosis, tubular atrophy, arteriolar hyalinosis, fibrointimal
      thickening) progressed in frequency and severity in both groups, although
      significantly more in the CsA group. Ten-year biopsy results showed that 92% of
      patients in the CsA-treated group and 65% in the control group had arteriolar
      hyalinosis lesions. When we focused on muscular arteriolar hyaline deposits more
      specific to CsA arteriolopathy, we observed these lesions in 68% of CsA patients
      and 28% of patients who had never received CsA. CsA was not the sole factor
      involved in the development of arteriolar hyalinosis and was independently
      associated with an increased risk of graft loss. In summary, we observed that
      histological lesions commonly attributed to CsA nephrotoxicity were not
      sufficiently specific to definitively diagnose CNI nephrotoxicity.

PMID- 21883916
TI  - Histological characteristics of calcineurin inhibitor toxicity--there is no such
      thing as specificity!

PMID- 21883917
TI  - Islet xenotransplantation using gal-deficient neonatal donors improves
      engraftment and function.
AB  - Significant deficiencies in understanding of xenospecific immunity have impeded
      the success of preclinical trials in xenoislet transplantation. Although
      galactose-alpha1,3-galactose, the gal epitope, has emerged as the principal
      target of rejection in pig-to-primate models of solid organ transplant, the
      importance of gal-specific immunity in islet xenotransplant models has yet to be
      clearly demonstrated. Here, we directly compare the immunogenicity, survival and
      function of neonatal porcine islets (NPIs) from gal-expressing wild-type (WT) or
      gal-deficient galactosyl transferase knockout (GTKO) donors. Paired diabetic
      rhesus macaques were transplanted with either WT (n = 5) or GTKO (n = 5) NPIs.
      Recipient blood glucose, transaminase and serum xenoantibody levels were used to
      monitor response to transplant. Four of five GTKO versus one of five WT
      recipients achieved insulin-independent normoglycemia; transplantation of WT
      islets resulted in significantly greater transaminitis. The WT NPIs were more
      susceptible to antibody and complement binding and destruction in vitro. Our
      results confirm that gal is an important variable in xenoislet transplantation.
      The GTKO NPI recipients have improved rates of normoglycemia, likely due to
      decreased susceptibility of xenografts to innate immunity mediated by complement
      and preformed xenoantibody. Therefore, the use of GTKO donors is an important
      step toward improved consistency and interpretability of results in future
      xenoislet studies.

PMID- 21883918
TI  - Bilateral native ureteral ligation without nephrectomy in the management of
      kidney transplant recipients with native proteinuria.
AB  - The aim of this study was to assess the safety of bilateral native ureteral
      ligation (BNUL) without nephrectomy in the management of native proteinuria in
      kidney transplant (KTx) recipients. We retrospectively studied 17 patients who
      underwent BNUL between 2002 and 2010 with a median preoperative 24 h protein
      concentration of 2140 (range 1020-25 000) mg/L. Fifteen of the 17 patients had
      focal segmental glomerulosclerosis as their primary renal disease and ligation
      was employed to facilitate the diagnosis of early recurrence. The BNUL was
      performed simultaneously with KTx in 14 patients. Surgical techniques were: open
      (n = 5), pure laparoscopic (n = 1) and a hybrid of hand-assisted laparoscopic
      surgical/open approach (n = 12) used at the time of transplantation via the
      transplant incision. At a median follow-up of 46 months (range 1-59), no patient
      had a complication related to BNUL and none required interventions associated
      with their native kidneys. BNUL without nephrectomy seems to be a safe technique
      to manage native proteinuria in renal transplant candidates.

PMID- 21883919
TI  - Induction of antiviral cytotoxic T cells by plasmacytoid dendritic cells for
      adoptive immunotherapy of posttransplant diseases.
AB  - Virus-associated hematologic malignancies (EBV lymphoproliferative disease) and
      opportunistic infections (CMV) represent a major cause of hematopoietic stem cell
      and solid organ transplantation failure. Adoptive transfer of antigen-specific T
      lymphocytes appears to be a major and successful immunotherapeutic strategy, but
      improvements are needed to reliably produce high numbers of virus-specific T
      cells with appropriate requirements for adoptive immunotherapy that would allow
      extensive clinical use. Since plasmacytoid dendritic cells (pDCs) are crucial in
      launching antiviral responses, we investigated their capacity to elicit
      functional antiviral T-cell responses for adoptive cellular immunotherapy using a
      unique pDC line and antigens derived from Influenza, CMV and EBV viruses.
      Stimulation of peripheral blood mononuclear cells from HLA-A*0201(+) donors by
      HLA-A0201 matched pDCs pulsed with viral-derived peptides triggered high levels
      of multi-specific and functional cytotoxic T-cell responses (up to 99%
      tetramer(+) CD8 T cells) in vitro. Furthermore, the central/effector memory
      cytotoxic T cells elicited by the pDCs strongly display antiviral activity upon
      adoptive transfer into a humanized mouse model that mimics a virus-induced
      malignancy. We provide a simple and potent method to generate virus-specific CTL
      with the required properties for adoptive cellular immunotherapy of post
      transplant diseases.

PMID- 21883920
TI  - Trends in wait-list mortality in children listed for heart transplantation in the
      United States: era effect across racial/ethnic groups.
AB  - We sought to evaluate trends in overall and race-specific pediatric heart
      transplant (HT) wait-list mortality in the United States (US) during the last 20
      years. We identified all children <18 years old listed for primary HT in the US
      during 1989-2009 (N = 8096, 62% White, 19% Black, 13% Hispanic and 6% Other)
      using the Organ Procurement and Transplant Network database. Wait-list mortality
      was assessed in four successive eras (1989-1994, 1995-1999, 2000-2004 and 2005
      2009). Overall wait-list mortality declined in successive eras (26%, 23%, 18% and
      13%, respectively). The decline across eras remained significant in adjusted
      analysis (hazard ratio [HR] 0.70 in successive eras, 95% confidence interval
      [CI], 0.67-0.74) and was 67% lower for children listed during 2005-2009 versus
      those listed during 1989-1994 (HR 0.33; CI, 0.28-0.39). In models stratified by
      race, wait-list mortality decreased in all racial groups in successive eras. In
      models stratified by era, minority children were not at higher risk of wait-list
      mortality in the most recent era. We conclude that the risk of wait-list
      mortality among US children listed for HT has decreased by two-thirds during the
      last 20 years. Racial gaps in wait-list mortality present variably in the past
      are not present in the current era.

PMID- 21883921
TI  - Nanoparticle delivery of mycophenolic acid upregulates PD-L1 on dendritic cells
      to prolong murine allograft survival.
AB  - Conventional immunosuppressive drug delivery requires high systemic drug levels
      to provide therapeutic benefit, but frequently results in toxic side effects.
      Novel drug delivery methods, such as FDA-approved poly(lactic-co-glycolic acid)
      (PLGA) nanoparticles (NPs), are promising drug delivery platforms to reduce drug
      doses and minimize toxicity. Using murine models of skin transplantation, we
      investigated whether PLGA NPs would effectively deliver mycophenolic acid (MPA),
      a common clinical immunosuppressant, and avoid the toxicity of conventional drug
      delivery. We found that intermittent treatment with NPs encapsulated with MPA (NP
      MPA) resulted in a significant extension of allograft survival than intermittent
      conventional MPA treatment even though the concentration of MPA within NP-MPA was
      a 1000-fold lower than conventional drug. Importantly, recipients who were
      administered NP-MPA intermittently avoided drug toxicity, whereas those treated
      with daily conventional drug manifested cytopenias. Dendritic cells (DCs)
      endocytosed NP-MPA to upregulate programmed death ligand-1 (PD-L1) and displayed
      a decreased ability to prime alloreactive T cells. Importantly, the ability of NP
      MPA to promote allograft survival was partly PD-L1 dependent. Collectively, this
      study indicates that NPs are potent drug delivery tools that extend allograft
      survival without drug toxicity.

PMID- 21883922
TI  - Association of BDNF and COMT genotypes with cognitive processing of anti-smoking
      PSAs.
AB  - Anti-smoking public service announcements (PSAs) often use persuasive arguments
      to attempt to influence attitudes about smoking. The persuasiveness of a PSA has
      previously been associated with factors that influence the cognitive processing
      of its message. Genetic factors that influence cognitive processing might thus
      affect individuals' responses to the persuasive arguments presented in PSAs. In
      the present study, we examined polymorphisms in the genes encoding brain-derived
      neurotrophic factor (BDNF Val66Met) and catechol-O-methyltransferase (COMT
      Val158Met), which affect cognitive processing in the prefrontal cortex, to
      identify genetic factors associated with self-reported outcomes of message
      processing, perceived effectiveness and quitting intentions among smokers viewing
      PSAs. A total of 120 smokers viewed sets of four PSAs that varied with respect to
      features of argument strength (AS) and message sensation value. We observed
      significant associations of BDNF genotype with central processing, narrative
      processing, perceived effectiveness of the anti-smoking PSAs and participant
      quitting intentions; the BDNF Met allele was associated with lower scores on all
      these measures. Central processing acted as a mediator of the association of
      genotype with quitting intentions and perceived effectiveness. There was a
      significant interaction of COMT genotype by AS in the model of narrative
      processing, such that individuals homozygous for the COMT Val allele reported
      higher narrative processing in the high-AS condition but not in the low-AS
      condition. To our knowledge, this is the first study to identify genetic factors
      associated with cognitive processing of anti-smoking PSAs.

PMID- 21883923
TI  - Mutation of the dyslexia-associated gene Dcdc2 impairs LTM and visuo-spatial
      performance in mice.
AB  - Developmental reading disorder (RD) affects 5-10% of school aged children, with a
      heritability of approximately 60%. Genetic association studies have identified
      several candidate RD susceptibility genes, including DCDC2; however, a direct
      connection between the function of these genes and cognitive or learning
      impairments remains unclear. Variants in DCDC2, a member of the doublecortin
      family of genes, have been associated in humans with RD and ADHD and Dcdc2 may
      play a role in neuronal migration in rats. In this study, we examined the effect
      of Dcdc2 mutation on cognitive abilities in mice using a visual attention and
      visuo-spatial learning and memory task. We show that both heterozygous and
      homozygous mutations of Dcdc2 result in persistent visuo-spatial memory deficits,
      as well as visual discrimination and long-term memory deficits. These behavioral
      deficits occur in the absence of neuronal migration disruption in the mutant
      mice, and may be comorbid with an anxiety phenotype. These are the first results
      to suggest a direct relationship between induced mutation in Dcdc2 and changes in
      behavioral measures. Dcdc2 mutant mice should prove useful in future studies
      designed to further dissect the underlying neural mechanisms that are impaired
      following Dcdc2 mutation.

PMID- 21883924
TI  - Genetic variants in the choline acetyltransferase (ChAT) gene are modestly
      associated with normal cognitive function in the elderly.
AB  - Genetic variants in the choline acetyltransferase (ChAT) gene have been suggested
      as risk factors for neurodegenerative Alzheimer's disease (AD). Here we tested
      the importance of genetic variants in the ChAT gene in normal cognitive function
      of elderly in a study sample of Danish twins and singletons (N = 2070). The ChAT
      rs3810950 A allele, which has been associated with increased risk for AD, was
      found to be associated with a decrease cognitive status evaluated by a five
      component cognitive composite score [P = 0.03, regression coefficient -0.30, 95%
      confidence interval (CI) -0.57 to -0.02], and the rs3810950 and rs8178990
      ancestral GC haplotype was also associated with better cross-sectional cognitive
      composite score (P = 0.04, regression coefficient 0.59, 95% CI 0.03 to 1.16).
      Growth curve model analyses applied to up to 10 years of follow-up data showed
      that the rs3810950 A allele was associated with a lower cognitive composite score
      and Mini Mental State Examination at the lowest age (73 years of age), and was
      lower in the whole interval 73-82 although the absolute difference became smaller
      with age. Stratification by the presence of the APOE epsilon4 allele showed that
      rs3810950 AG/non-APOE epsilon4 carriers and rs3810950 AA/APOE epsilon4 carriers
      were associated with a lower cognitive composite score in younger elderly 73-83
      years of age, similar to previous reports of association with AD.

PMID- 21883925
TI  - Complete clearance of calciphylaxis following combined treatment with cinacalcet
      and sodium thiosulfate.

PMID- 21883926
TI  - Lichen planus of nails - successful treatment with Alitretinoin.

PMID- 21883927
TI  - Special issue: Protein structure and proteomics: introduction.

PMID- 21883928
TI  - Multiple NF-Y-binding CCAAT boxes are essential for transcriptional regulation of
      the human C7orf24 gene, a novel tumor-associated gene.
AB  - Human chromosome 7 ORF 24 (C7orf24) has been identified as a tumor-related
      protein, and shown to be a gamma-glutamyl cyclotransferase. In the current study,
      we characterized the promoter region of the human C7orf24 gene to explore the
      transcriptional regulation of the gene. We revealed that the human C7orf24
      promoter is a TATA-less promoter, containing five CCAAT boxes aligned in a
      forward orientation. By performing a luciferase reporter assay with 5'-deleted
      and site-directed mutated constructs in HeLa, MCF-7 and IMR-90 cells, we found
      that three proximal CCAAT boxes are important for basal transcription.
      Electrophoretic mobility gel shift assay and chromatin immunoprecipitation assay
      demonstrated that NF-Y specifically bound to all three CCAAT boxes. In addition,
      the mRNA and protein expression levels of C7orf24 were significantly reduced in
      HeLa cells depleted of NF-YB, a subunit of NF-Y. These results suggested that NF
      Ys bound to the three proximal CCAAT boxes play a central role in the
      transcription of the gene. Furthermore, as in the case of other genes transcribed
      under the control of multiple NF-Ys, such as human E2f1 and cyclin b1, the
      C7orf24 gene expression profile oscillated during the cell cycle, implying that
      C7orf24 is a novel cell cycle-associated gene.

PMID- 21883929
TI  - The AMPK/SNF1/SnRK1 fuel gauge and energy regulator: structure, function and
      regulation.
AB  - All life forms on earth require a continuous input and monitoring of carbon and
      energy supplies. The AMP-activated kinase (AMPK)/sucrose non-fermenting1
      (SNF1)/Snf1-related kinase1 (SnRK1) protein kinases are evolutionarily conserved
      metabolic sensors found in all eukaryotic organisms from simple unicellular fungi
      (yeast SNF1) to animals (AMPK) and plants (SnRK1). Activated by starvation and
      energy-depleting stress conditions, they enable energy homeostasis and survival
      by up-regulating energy-conserving and energy-producing catabolic processes, and
      by limiting energy-consuming anabolic metabolism. In addition, they control
      normal growth and development as well as metabolic homeostasis at the organismal
      level. As such, the AMPK/SNF1/SnRK1 kinases act in concert with other central
      signaling components to control carbohydrate uptake and metabolism, fatty acid
      and lipid biosynthesis and the storage of carbon energy reserves. Moreover, they
      have a tremendous impact on developmental processes that are triggered by
      environmental changes such as nutrient depletion or stress. Although intensive
      research by many groups has partly unveiled the factors that regulate
      AMPK/SNF1/SnRK1 kinase activity as well as the pathways and substrates they
      control, several fundamental issues still await to be clarified. In this review,
      we will highlight these issues and focus on the structure, function and
      regulation of the AMPK/SNF1/SnRK1 kinases.

PMID- 21883930
TI  - Biological characteristics of two lysines on human serum albumin in the high
      affinity binding of 4Z,15Z-bilirubin-IXalpha revealed by phage display.
AB  - 4Z,15Z-bilirubin-IXalpha (4Z,15Z-BR), an endogenous compound that is sparingly
      soluble in water, binds human serum albumin (HSA) with high affinity in a
      flexible manner. A phage library displaying recombinant HSA domain II was
      constructed, after three rounds of panning against immobilized 4Z,15Z-BR, and
      eight clones with high affinity for the pigment were found to contain conserved
      basic residues, such as lysine or arginine, at positions 195 and 199. The wild
      type and two mutants, K195A and K199A, of whole HSA as well as stand-alone domain
      II were expressed in Pichia pastoris for ligand-binding studies. The binding of
      4Z,15Z-BR to the K195A and K199A mutants was decreased in both whole HSA and the
      domain II proteins. The P-helicity conformer (P-form) of 4Z,15Z-BR was found to
      preferentially bind to the wild types and the K195A mutants, whereas the M-form
      bound to the K199A mutants. Photoconversion experiments showed that the P-form of
      4Z,15Z-BR was transformed into highly water-soluble isomers at a much faster rate
      than the M-form. In addition, the M-form of 4Z,15Z-BR showed higher affinity for
      domain I than for domain II. The present findings suggest that, whereas both
      Lys195 and Lys199 in subdomain IIA are important for the high-affinity binding of
      4Z,15Z-BR, Lys199 plays a more prominent role in the elimination of 4Z,15Z-BR.

PMID- 21883931
TI  - Circadian expression of steroidogenic cytochromes P450 in the mouse adrenal gland
      -involvement of cAMP-responsive element modulator in epigenetic regulation of
      Cyp17a1.
AB  - The cytochrome P450 (CYP) genes Cyp51, Cyp11a1, Cyp17a1, Cyb11b1, Cyp11b2 and
      Cyp21a1 are involved in the adrenal production of corticosteroids, whose
      circulating levels are circadian. cAMP signaling plays an important role in
      adrenal steroidogenesis. By using cAMP responsive element modulator (Crem)
      knockout mice, we show that CREM isoforms contribute to circadian expression of
      steroidogenic CYPs in the mouse adrenal gland. Most striking was the CREM
      dependent hypomethylation of the Cyp17a1 promoter at zeitgeber time 12, which
      resulted in higher Cyp17a1 mRNA and protein expression in the knockout adrenal
      glands. The data indicate that products of the Crem gene control the epigenetic
      repression of Cyp17 in mouse adrenal glands.

PMID- 21883932
TI  - Early use of negative pressure therapy in combination with silver dressings in a
      difficult breast abscess.
AB  - Combining silver-based dressings with negative pressure therapy after radical
      excision of chronically infected breast disease is a novel application of two
      technologies. One patient with complex, chronic, infected breast disease
      underwent radical excision of the affected area and was treated early with a
      combination of silver-based dressings and topical negative pressure therapy. The
      wound was then assessed sequentially using clinical measurements of wound area
      and depth, pain severity scores and level of exudation. It is possible to combine
      accepted techniques with modern dressing technologies that result in a positive
      outcome. In this case, the combination of a silver-based dressing with negative
      pressure therapy following radical excision proved safe and was well tolerated by
      the patient. Full epithelisation of the wound was achieved and there was no
      recurrence of the infection for the duration of the treatment.

PMID- 21883933
TI  - Necrotising fasciitis due to Absidia corymbifera in wounds dressed with non
      sterile bandages.
AB  - We present three cases of Absidia corymbifera necrotising fasciitis presenting to
      our centre within 1 month of each other. All patients had wound dressings with
      non sterile crepe bandages at peripheral centres. One patient was lost to follow
      up, another improved on timely antifungal therapy, while the last patient
      succumbed to disseminated infection. We propose that traumatic and deep wounds be
      dressed with sterile roller bandages to prevent outbreaks of wound zygomycosis.

PMID- 21883934
TI  - In vitro and in vivo studies on matrix metalloproteinases interacting with small
      intestine submucosa wound matrix.
AB  - Small intestine submucosa (SIS), a bioactive extracellular matrix (ECM)
      containing critical components of the ECM including collagens, proteoglycans, and
      glycosaminoglycans, has been widely used for wound healing. The purpose of this
      study was to investigate the interaction between SIS and matrix
      metalloproteinases (MMPs). MMP-1, MMP-2, and MMP-9 displayed different binding
      affinities, indicated by a loss in activity in solution upon incubation with SIS
      at 53.8%, 85.9%, and 36.9% over 24 hours, respectively. A cell migration study
      was conducted to evaluate the effects of MMPs and SIS on keratinocytes. The
      results indicated that MMPs inhibit keratinocyte migration in vitro, and that the
      inhibition can be significantly reduced by pre-incubating the MMP solution with
      SIS. To evaluate activity in vivo a diabetic mouse wound healing study was
      conducted. Biopsy samples were collected on different days for analysis of MMP
      levels by gelatin zymography. MMP activity was found to be attenuated by SIS
      treatment on day 3 after wounding. On day 7, the attenuation became less
      significant indicating that the MMP binding ability of SIS had become saturated.
      SIS was able to reduce MMP activity immediately, and may reduce the inhibitory
      effects of MMPs on keratinocyte migration.

PMID- 21883935
TI  - Skin necrosis of scrotum due to endovascular embolisation: a case report.
AB  - The aim of our case report was to analyse the results obtained with the
      Matriderm(r) system and autologous skin grafting for the surgical treatment of
      skin necrosis of scrotum as a result of endovascular embolisation. We recruited
      one patient with scrotum skin necrosis as a result of endovascular embolisation
      admitted at the department of Plastic and Reconstructive Surgery, University of
      Rome 'Tor Vergata'. The patient underwent Matriderm(r) system and autologous skin
      grafting for skin necrosis treatment. After a single treatment, reduction of the
      skin necrosis was obtained, after 30 days from the surgical treatment. Patient
      experienced a reduction in pain and a complete restoration of the loss in volume
      and quality of skin was noticed. Matriderm(r) system and autologous skin grafting
      is a simple, safe and feasible technique. When comparing this treatment with
      others, Matriderm(r) is a simpler, more economic and less time-consuming method,
      and does not require sophisticated laboratory facilities.

PMID- 21883937
TI  - Diabetic foot infections: microbiological aspects, current and future antibiotic
      therapy focusing on methicillin-resistant Staphylococcus aureus.
AB  - Diabetic patients are at increased risk of complicated skin, skin structure and
      bone infections including infections of diabetic foot ulcerations (DFU). Analyses
      of epidemiology and microbial pathogenicity show that staphylococci seem to be
      predestined to induce such infections. In addition, multidrug resistance
      particularly due to an increasing prevalence of methicillin-resistant
      Staphylococcus aureus (MRSA) seems to be the challenge for effective antibiotic
      therapy. With regard to infections with MRSA, classical agents like vancomycin,
      linezolid, fosfomycin or trimethroprim-sulphametoxazol might be agents of choice
      in DFU. New-generation drugs including broad-spectrum tetracyclines like
      tigecycline, first and second generation of cyclic lipopeptides, anti-MRSA beta
      lactams including ceftobiprole and anti-MRSA antibodies are developed or in
      progress and the hope for the future.

PMID- 21883936
TI  - Acceleration of wound repair by curcumin in the excision wound of mice exposed to
      different doses of fractionated gamma radiation.
AB  - Fractionated irradiation (IR) before or after surgery of malignant tumours causes
      a high frequency of wound healing complications. Our aim was to investigate the
      effect of curcumin (CUM) on the healing of deep excision wound of mice exposed to
      fractionated IR by mimicking clinical conditions. A full-thickness dermal
      excision wound was created on the shaved dorsum of mice that were orally
      administered or not with 100 mg of CUM per kilogram body weight before partial
      body exposure to 10, 20 or 40 Gy given as 2 Gy/day for 5, 10 or 20 days. The
      wound contraction was determined periodically by capturing video images of the
      wound from day 1 until complete healing of wounds. Fractionated IR caused a dose
      dependent delay in the wound contraction and prolonged wound healing time,
      whereas CUM administration before fractionated IR caused a significant elevation
      in the wound contraction and reduced mean wound healing time. Fractionated IR
      reduced the synthesis of collagen, deoxyribonucleic acid (DNA) and nitric oxide
      (NO) at different post-IR times and treatment of mice with CUM before IR elevated
      the synthesis of collagen, DNA and NO significantly. Histological examination
      showed a reduction in the collagen deposition, fibroblast and vascular densities
      after fractionated IR, whereas CUM pre-treatment inhibited this decline
      significantly. Our study shows that CUM pre-treatment accelerated healing of
      irradiated wound and could be a substantial therapeutic strategy in the
      management of irradiated wounds.

PMID- 21883938
TI  - Investigation of mechanisms involved in (-)-borneol-induced vasorelaxant response
      on rat thoracic aorta.
AB  - The monoterpene (-)-borneol is present in essential oils of several medicinal
      plants. The aim of this study was to evaluate (-)-borneol effects on rat thoracic
      aorta artery rings. The cumulative addition of (-)-borneol (10(-9) -3 * 10(-4) 
      M) on a phenylephrine-induced pre-contraction (10(-6)  M) promoted a vasorelaxant
      effect in a concentration-dependent manner and independent of vascular
      endothelium. A similar effect was obtained on KCl-induced pre-contractions (80
      mM). (-)-Borneol (10(-5) -3 * 10(-4 ) M) inhibited contractions induced by
      cumulative addition of CaCl2 (10(-6) -3 * 10(-2)  M) in depolarizing medium
      without Ca(2+) in a concentration-dependent manner. On S-(-) Bay K 8644-induced
      pre-contractions (10(-7)  M), (-)-borneol did not induce significant changes
      compared with KCl-induced pre-contractions. In a Ca(2+) -free medium, (-)-borneol
      (10(-5) , 10(-4) or 10(-3)  M) interfered in calcium mobilization from
      phenylephrine (10(-6)  M)- or caffeine (20 mM)-sensitive intracellular stores.
      The involvement of K(+) channels was evaluated by tetraethylammonium (3 mM), 4
      aminopyridine (1 mM) and glibenclamide (10(-5)  M) pre-treatment, and (-)-borneol
      induced vasorelaxation was markedly attenuated. Thus, this vasorelaxant effect
      can probably be attributed to calcium influx blockade through voltage-operated
      calcium channels (CaV L), calcium mobilization from intracellular stores and
      potassium channels activation. 

PMID- 21883939
TI  - Reactive oxygen species and endothelial function--role of nitric oxide synthase
      uncoupling and Nox family nicotinamide adenine dinucleotide phosphate oxidases.
AB  - The healthy endothelium prevents platelet aggregation and leucocyte adhesion,
      controls permeability to plasma components and maintains vascular integrity.
      Damage to the endothelium promotes endothelial dysfunction characterized by:
      altered endothelium-mediated vasodilation, increased vascular reactivity,
      platelet aggregation, thrombus formation, increased permeability, leucocyte
      adhesion and monocyte migration. Molecular processes contributing to these
      phenomena include increased expression of adhesion molecules, synthesis of pro
      inflammatory and pro-thrombotic factors and increased endothelin-1 secretion.
      Decreased nitric oxide bioavailability and increased generation of reactive
      oxygen species (ROS) are among the major molecular changes associated with
      endothelial dysfunction. A critical source of endothelial ROS is a family of non
      phagocytic nicotinamide adenine dinucleotide phosphate (NADPH) oxidases,
      including the prototypic Nox2-based NADPH oxidases, Nox1, Nox4 and Nox5. Other
      possible sources include mitochondrial electron transport enzymes, xanthine
      oxidase, cyclooxygenase, lipoxygenase and uncoupled nitric oxide synthase (NOS).
      Cross-talk between ROS-generating enzymes, such as mitochondrial oxidases and
      Noxs, is increasingly implicated in cellular ROS production. The present review
      discusses the importance of endothelial ROS in health and disease and focuses on
      the major ROS-generating systems in the endothelium, namely uncoupled endothelial
      nitric oxide synthase and NADPH oxidases.

PMID- 21883940
TI  - Structural alterations in small resistance arteries in obesity.
AB  - In cardiovascular and metabolic diseases, small resistance arteries may show the
      presence of structural alterations. In particular, in essential hypertension, an
      increased media-to-lumen ratio of subcutaneous small arteries with no change in
      the total amount of vascular wall tissue (eutrophic remodelling) has already been
      described several years ago. Similar alterations have been demonstrated also in
      patients with diabetes mellitus and obesity; in this case, however, a more
      evident contribution of vascular smooth muscle cell growth (hypertrophic
      remodelling) is present. This review addresses the effects of obesity on small
      resistance artery structure. Similar to diabetic patients, obese patients show an
      increased media-to-lumen ratio of subcutaneous small arteries, which appears
      associated with hypertrophic remodelling, as demonstrated by an increase in media
      cross-sectional area. Endothelial dysfunction evaluated as vasodilator response
      to acetylcholine has also been observed. Several studies have shown that
      increased media-to-lumen ratio of subcutaneous small resistance arteries
      possesses a prognostic significance in relation to cardiovascular outcome.
      Appropriate antihypertensive treatment may improve microvascular alterations both
      in essential hypertension and in type 2 diabetes mellitus. In obesity, a
      pronounced weight loss may improve microvascular structure. However, further
      studies are needed to elucidate the effects of other pharmacological and non
      pharmacological interventions in obesity.

PMID- 21883941
TI  - Sexual behaviors and situational characteristics of most recent male-partnered
      sexual event among gay and bisexually identified men in the United States.
AB  - INTRODUCTION: Recent nationally representative studies documenting event-level
      sexual behavior have included samples that are predominantly heterosexual,
      resulting in limited information on the sexual repertoire of gay and bisexually
      identified men. AIM: This study sought to document the sexual behaviors that gay
      and bisexually identified men report during their most recent male-partnered
      sexual event and to describe the situational characteristics and participants'
      evaluation of these events. METHODS: Via an internet-based survey, data were
      collected from 24,787 gay and bisexually identified men (ages 18-87 years) from
      50 US states and the District of Columbia. MAIN OUTCOME MEASURES: Measures
      included items related to sociodemographics, recent sexual behavior history,
      situational characteristics, orgasm, and ratings of arousal and pleasure.
      RESULTS: Participants' mean age was 39.2 years; ethnicities included white
      (84.6%), Latino (6.4%), and African American (3.6%); and most men (79.9%)
      identified as homosexual. The most commonly reported behavior was kissing a
      partner on the mouth (74.5%), followed by oral sex (72.7%), and partnered
      masturbation (68.4%). Anal intercourse occurred among less than half of
      participants (37.2%) and was most common among men ages 18-24 (42.7%). Sex was
      most likely to occur in the participant's home (46.8%), with less frequently
      reported locations including hotels (7.4%) and public spaces (3.1%). The number
      of behaviors engaged in during last sexual event varied with most (63.2%)
      including 5-9 different sexual behaviors. CONCLUSIONS: These data provide one of
      the first examinations of sexual behaviors during the most recent male-partnered
      sexual event among gay and bisexually identified men in the United States.
      Findings from this study suggest that gay and bisexually identified men have a
      diverse sexual repertoire and that partnered sexual behaviors are not limited
      solely to acts of penile insertion.

PMID- 21883942
TI  - Potential risks of chronic sildenafil use for priapism in sickle cell disease.
AB  - INTRODUCTION: Priapism is a common concern in sickle cell disease. With a high
      frequency of recurrences and serious long-term sequela, a preventative, rather
      than traditionally reactive approach, needs to be taken in these patients.
      Reports have shown successful use of sildenafil as a prophylactic treatment but
      have failed to address adverse outcomes, including vasoocclusive pain crises, of
      chronic sildenafil therapy in sickle cell patients. AIMS: We wish to draw
      attention to the potential adverse outcomes of this therapy on the overall state
      of the patient's disease for consideration in future studies. METHODS: We used
      sildenafil in a patient suffering from almost daily attacks of priapism. RESULTS:
      Sildenafil was successful in decreasing the frequency of priapism; however, our
      patient experienced an increased frequency of vasoocclusive crises, something not
      previously addressed. CONCLUSION: Future studies of sildenafil use in sickle cell
      disease need to assess the global state of the disease, not just the frequency of
      priapism.

PMID- 21883943
TI  - The importance of sexual self-disclosure to sexual satisfaction and functioning
      in committed relationships.
AB  - INTRODUCTION: Past research indicates that sexual self-disclosure, or the degree
      to which an individual is open with his or her partner about sexual preferences,
      is a key aspect of sexual satisfaction and that partner's lack of knowledge about
      one's sexual preferences is associated with persistent sexual dysfunction. AIMS:
      To replicate and extend past research by examining (i) how one's own levels of
      sexual self-disclosure are related to one's own sexual health (after controlling
      for partner's levels of sexual self-disclosure); (ii) how one's partner's levels
      of sexual self-disclosure are associated with one's own sexual health (after
      controlling for one's own levels of sexual self-disclosure); and (iii) whether
      gender moderates the associations between sexual self-disclosure and sexual
      health. MAIN OUTCOME MEASURES: Scores from the Golombok Rust Inventory of Sexual
      Satisfaction and the Sexual Communication Satisfaction Scale. METHODS: A cross
      sectional dyadic study using a convenience sample of 91 heterosexual couples in
      long-term committed relationships. Data were analyzed using the Actor-Partner
      Interdependence Model. RESULTS: One's own level of sexual self-disclosure is
      positively associated with one's own sexual satisfaction, beta = -0.24, t(172.85)
      = -3.50, P < 0.001. Furthermore, partner's level of sexual self-disclosure is
      associated with men's sexual satisfaction but not with women's sexual
      satisfaction, beta = -0.45, t(86.81) = -4.06, P < 0.001 and beta = 0.02, t(87.00)
      = 0.20, ns, respectively. The association between own self-disclosure and sexual
      problems is stronger for women as compared with men, beta = -0.72, t(87.00) = 
      6.31, P < 0.001 and beta = -0.24, t(86.27) = -3.04, P < 0.01, respectively.
      CONCLUSIONS: Our results demonstrate that sexual self-disclosure is significantly
      associated with sexual satisfaction and functioning for both men and women,
      albeit in different ways. Our findings underscore the importance of sexual self
      disclosure and highlight the importance of the interpersonal level of analysis in
      understanding human sexuality.

PMID- 21883944
TI  - Outcomes with the "V" implantation technique vs. standard technique for
      testosterone pellet therapy.
AB  - INTRODUCTION: Standard technique (ST) for implantation of testosterone pellets
      involves making a single linear track in the subcutaneous tissue of the buttock
      from the incision. After our initial experience with this modality, we modified
      this surgical technique to our current "V" technique (VT). This involves two
      tracks both caudally directed and emanating from the same skin incision but
      angulated approximately 10-15 degrees apart. While this allows additional pellets
      to be inserted more easily, and increased space to place those pellets further
      from the skin incision, it minimally increases the surgical procedure. AIM: We
      sought to examine the impact of this technical modification on therapeutic
      efficacy and surgical complication rates. METHODS: Retrospective chart review of
      all patients treated with testosterone pellets at our institution. MAIN OUTCOME
      MEASURE: Complication rates for infection, extrusion, hematoma, and pain.
      RESULTS: One hundred sixty-eight patients underwent 281 implantation procedures
      (40 via ST and 241 via VT). The mode number of pellets used with ST was 8 (range
      6-8) and with VT was 10 (range 10-13). Incidence of pellet extrusion was 7.5%
      with ST and 0.8% with VT. Infection complicated ST in 5% of cases but only 1.2%
      with VT. No cases of hematoma were seen with ST but 1.2% of VT cases. Pain
      prompting discontinuation of therapy was seen in 7.5% with ST and 1.7% with VT.
      Significant pain without discontinuation was seen in 5% with ST and 1.2% with VT.
      Only in 1 of the 3 cases of hematoma was the individual on blood thinners. Fifty
      eight other insertions were performed on blood thinners without significant
      hematoma. None of the individuals who developed infection or bleeding required
      additional surgical therapy. CONCLUSIONS: VT allows successful placement of
      larger number of pellets, with low rates of complications, especially extrusion,
      even in men on anticoagulants.

PMID- 21883945
TI  - Exercise training improves the defective centrally mediated erectile responses in
      rats with type I diabetes.
AB  - INTRODUCTION: Erectile dysfunction is a serious and common complication of
      diabetes mellitus. Apart from the peripheral actions, central mechanisms are also
      responsible for the penile erection. AIM: The goal of the present study was to
      determine the impact of exercise training (ExT) on the centrally mediated
      erectile dysfunction in streptozotocin (STZ)-induced type I diabetic (T1D) rats.
      METHODS: Male Sprague-Dawley rats were injected with STZ to induce diabetes
      mellitus. Three weeks after STZ or vehicle injections, rats were assigned to
      either ExT (treadmill running for 3-4 weeks) or sedentary groups to produce four
      experimental groups: control + sedentary, T1D + sedentary, control + ExT, and T1D
      + ExT. MAIN OUTCOME MEASURE: After 3-4 weeks ExT, central N-methyl-D-aspartic
      acid (NMDA) or sodium nitroprusside (SNP)-induced penile erectile responses were
      measured. Neuronal nitric oxide synthase (nNOS) expression in the paraventricular
      nucleus (PVN) of the hypothalamus was measured by using histochemistry, real time
      polymerase chain reaction (PCR) and Western blot approaches. RESULTS: In rats
      with T1D, ExT significantly improved the blunted erectile response, and the
      intracavernous pressure changes to NMDA (50 ng) microinjection within the PVN
      (T1D + ExT: 3.0 +/- 0.6 penile erection/rat; T1D + sedentary: 0.5 +/- 0.3 penile
      erection/rat within 20 minutes, P < 0.05). ExT improved erectile dysfunction
      induced by central administration of exogenous nitric oxide (NO) donor, SNP in
      T1D rats. Other behavior responses including yawning and stretching, induced by
      central NMDA and SNP microinjection were also significantly increased in T1D rats
      after ExT. Furthermore, we found that ExT restored the nNOS mRNA and protein
      expression in the PVN in T1D rats. CONCLUSIONS: These results suggest that ExT
      may have beneficial effects on the erectile dysfunction in diabetes through
      improvement of NO bioavailability within the PVN. Thus, ExT may be used as
      therapeutic modality to up-regulate nNOS within the PVN and improve the central
      component of the erectile dysfunction in diabetes mellitus.

PMID- 21883946
TI  - Sex hormone levels, genetic androgen receptor polymorphism, and anxiety in >=50
      year-old males.
AB  - INTRODUCTION: While associations between somatic changes and sex hormone levels
      in aging men have been explored in many studies, the association of testosterone
      and estradiol with psychic symptoms other than depression and the role of the
      genetically determined CAG repeat (CAGn) polymorphism of the androgen receptor
      (AR) have received much less attention. AIM: The purpose of this article is to
      investigate the associations between general anxiety, phobic anxiety and panic
      with sex hormone levels and the genetic androgen receptor polymorphism in aging
      males. METHODS: This cross-sectional study of males aged >=50 years included 120
      consecutive patients of the Department of Psychosomatics and Psychotherapy, 76
      consecutive patients of the Andrology Clinic, and 100 participants from the
      general population; all of them completed the Brief Symptom Inventory (BSI), the
      Aging Males' Symptoms (AMS) Scale, and the Patient Health Questionnaire (PHQ-9).
      Morning blood samples were analyzed for total and free testosterone, estradiol,
      sex hormone-binding globulin (SHBG), and the CAGn AR polymorphism. Psychosomatic
      patients also underwent psychiatric assessment. MAIN OUTCOME MEASURES: Scores on
      the Anxiety subscales of the BSI and PHQ, Anxiety disorders according to
      International Classification of Diseases, 10th revision (ICD-10). RESULTS: The
      two clinical samples had significantly longer CAGn of the AR and higher anxiety
      levels compared to the population sample. Anxiety scores were positively
      correlated with CAGn in psychosomatic patients and in andrological patients, in
      the latter also with estradiol levels, while the population sample showed no
      significant correlations between anxiety scores, CAGn and sex hormones. Anxiety
      cases according to BSI, PHQ, and ICD-10 had significantly longer CAGn of the AR
      when compared to the other participants, but there were no significant
      differences in testosterone or free testosterone levels. CONCLUSIONS: Our results
      indicate that genetically determined long CAGn of the AR is an independent risk
      factor for higher anxiety, panic and phobic anxiety levels.

PMID- 21883947
TI  - Vaginal orgasm is related to better mental health and is relevant to evolutionary
      psychology: a response to Zietsch et al.

PMID- 21883948
TI  - The effect of major depression on sexual function in women.
AB  - INTRODUCTION: Eleven hundred eighty-four depressed women were entered into five
      short-term (8 weeks) studies of gepirone-extended release (ER) vs. placebo for
      treatment of major depressive disorder (MDD) (134001, 134002, and 134017), or
      atypical depressive disorder (ADD) (134004 and 134006). The effect of depression
      on sexual function was examined prior to treatment. AIM: To determine the effect
      of depression on the prevalence of Diagnostic and Statistical Manual Fourth
      Edition (DSM-IV) sexual dysfunction diagnoses and the Derogatis Inventory of
      Sexual Function (DISF) total score and domain scores and to measure the effect of
      severity of depression. MAIN OUTCOME MEASURES: Hamilton Depression Rating Scale
      (HAMD-17), DSM-IV diagnoses, and DISF total and domain scores. METHODS: DSM-IV
      diagnoses--hypoactive sexual desire disorder (HSDD), sexual aversion disorder
      (SAD), female arousal disorder (FAD), and female orgasmic disorder (FOD)--were
      made by a trained psychiatrist. The HAMD-17 measured antidepressant efficacy. The
      DISF or its self-report version measured sexual function. To access the effect of
      severity of depression, baseline HAMD-17 scores were stratified as mild (<18),
      moderate (19-22), severe (23-25), or extreme (26-33). All measures were taken at
      baseline. RESULTS: In this depressed female population, prevalence rates were
      HSDD 17.7%, SAD 3.4%, FAD 5.8%, and FOD 7.7%. These rates for females are within
      the reported normal (nondepressed) values. However, DISF scores are one or more
      standard deviations below population norms for total score. DISF domains are not
      equally affected: orgasm is most impaired, while sexual desire and sexual arousal
      are somewhat preserved. Higher HAMD scores result in lower DISF scores (greater
      sexual dysfunction). CONCLUSIONS: In women, depression affects DISF scores more
      than DSM-IV diagnoses for sexual dysfunction. With increasing severity of
      depression (increased HAMD scores), sexual dysfunction becomes greater (lower
      DISF scores). For equal HAMD scores, DISF scores for MDD and ADD are the same.

PMID- 21883949
TI  - Satisfying sexual events as outcome measures in clinical trial of female sexual
      dysfunction.
AB  - INTRODUCTION: Assessing the sexual response in women with female sexual
      dysfunctions (FSDs) in clinical trials remains difficult. Part of the challenge
      is the development of meaningful and valid end points that capture the complexity
      of women's sexual response. AIM: The purpose of this review is to highlight the
      shortcomings of daily diaries and the limitations of satisfying sexual events
      (SSEs) as primary end points in clinical trials of women with hypoactive sexual
      desire disorder (HSDD) as recommended by the Food and Drug Administration (FDA)
      in their draft guidance on standards for clinical trials in women with FSD.
      METHODS: Clinical trials in women with HSDD using SSEs as primary end points were
      reviewed. MAIN OUTCOME MEASURES: The agreement between three outcome measures
      (SSEs, desire, and distress) was assessed to illustrate to what degree
      improvements in SSEs were in agreement with improvements in sexual desire and/or
      personal distress. RESULTS: Nine placebo-controlled randomized trials in women
      with HSDD were reviewed: seven with transdermal testosterone and two with
      flibanserin. In four trials, all using transdermal testosterone 300 ug/day had
      agreement between changes in SSEs, desire, and distress. In five studies
      (testosterone 300 ug/day, n = 2; testosterone 150 ug/day, n = 1; flibanserin n =
      2), changes in SSEs did not correlate with changes in desire and/or distress and
      vice versa. It should be noted that in the flibanserin trials, SSEs did correlate
      with desire assessed using the Female Sexual Function Index but not when it was
      assessed using the eDiary. CONCLUSIONS: Findings in the literature do not
      uniformly support the recommendations from the FDA draft guidance to use diary
      measures in clinical trials of HSDD as primary end points. Patient-reported
      outcomes appear to be better suited to capture the multidimensional and more
      subjective information collected in trials of FSD.

PMID- 21883950
TI  - Simultaneous penile-vaginal orgasm is associated with sexual satisfaction.

PMID- 21883951
TI  - Neural activation toward erotic stimuli in homosexual and heterosexual males.
AB  - INTRODUCTION: Studies investigating sexual arousal exist, yet there are diverging
      findings on the underlying neural mechanisms with regard to sexual orientation.
      Moreover, sexual arousal effects have often been confounded with general arousal
      effects. Hence, it is still unclear which structures underlie the sexual arousal
      response in homosexual and heterosexual men. AIM: Neural activity and subjective
      responses were investigated in order to disentangle sexual from general arousal.
      Considering sexual orientation, differential and conjoint neural activations were
      of interest. METHODS: The functional magnetic resonance imaging (fMRI) study
      focused on the neural networks involved in the processing of sexual stimuli in 21
      male participants (11 homosexual, 10 heterosexual). Both groups viewed pictures
      with erotic content as well as aversive and neutral stimuli. The erotic pictures
      were subdivided into three categories (most sexually arousing, least sexually
      arousing, and rest) based on the individual subjective ratings of each
      participant. MAIN OUTCOME MEASURES: Blood oxygen level-dependent responses
      measured by fMRI and subjective ratings. RESULTS: A conjunction analysis revealed
      conjoint neural activation related to sexual arousal in thalamus, hypothalamus,
      occipital cortex, and nucleus accumbens. Increased insula, amygdala, and anterior
      cingulate gyrus activation could be linked to general arousal. Group differences
      emerged neither when viewing the most sexually arousing pictures compared with
      highly arousing aversive pictures nor compared with neutral pictures. CONCLUSION:
      Results suggest that a widespread neural network is activated by highly sexually
      arousing visual stimuli. A partly distinct network of structures underlies sexual
      and general arousal effects. The processing of preferred, highly sexually
      arousing stimuli recruited similar structures in homosexual and heterosexual
      males.

PMID- 21883952
TI  - Use of pelvic floor ultrasound to assess pelvic floor muscle function in
      Urological Chronic Pelvic Pain Syndrome in men.
AB  - INTRODUCTION: An important cause or maintaining factor for pain in Urological
      Chronic Pelvic Pain Syndrome (UCPPS) may be pelvic floor muscle (PFM)
      dysfunction, which may also be implicated in sexual dysfunction and influenced by
      psychosocial factors. Pelvic floor ultrasound is a noninvasive, reliable, and
      relatively simple method to assess PFM morphology and function and can be
      assessed by the anorectal angle (ARA) and levator plate angle (LPA). AIMS: The
      aim of the present study was to examine PFM morphology in men with UCPPS as
      compared with controls and to examine the correlation with pain and psychosocial
      measures. METHODS: Our participants were 24 men with UCPPS and 26 controls. A GE
      Voluson E8 ultrasound probe was placed on the perineum, and three-dimensional
      images were taken at rest and during PFM contraction. MAIN OUTCOME MEASURES: The
      main outcomes were ARA and LPA at rest and contraction. Participants also
      completed the National Institute of Health (NIH) Chronic Prostatitis Symptom
      Index, Male Sexual Health Questionnaire, State Anxiety Inventory, and Pain
      Catastrophizing Scale. RESULTS: Men with UCPPS had more acute ARAs than controls
      both at rest and during contraction. The two groups did not differ in LPA at
      rest; however, men with UCPPS had significantly more acute angles during
      contraction and LP excursion. Acute ARAs were positively correlated with greater
      pain report and sexual dysfunction. Anxiety was correlated with more acute ARAs
      and more obtuse LPAs. CONCLUSIONS: Three implications can be drawn from the
      findings. First, ARA at rest and during contraction as well as LP angle during
      contraction and LPA excursion separates men with UCPPS from controls. Second, ARA
      at rest and during contraction was correlated with pain and sexual dysfunction,
      while LPA at rest was related to anxiety. Third, pelvic floor ultrasound has the
      potential to be a useful and objective method of assessing PFM morphology in
      UCPPS.

PMID- 21883953
TI  - Characterization of erectile function in elastin haploinsufficicent mice.
AB  - INTRODUCTION: Elastin fibers confer passive recoil to many tissues including the
      lung, skin, and arteries. In the penis, elastin is present in sinusoids,
      arterioles, and in the tunica albuginea. Although decreased penile elastin has
      been reported in men with erectile dysfunction, the exact role of elastin in
      physiologic processes integral to erection remains speculative. AIM: The aim of
      this study was to characterize erectile function in elastin-deficient mice.
      METHODS: Elastin haploinsufficient mice (Eln(+/-) ) and aged match Eln(+/+) (Wt)
      mice were used. Cavernosum was removed from some mice for quantification of
      elastin, collagen, and smooth muscle actin. Ex vivo assessment of contractile
      force generation was performed by myography. In vivo assessment of intracorporal
      pressure normalized to mean arterial pressure in response to electrical
      stimulation of the cavernosal nerve was measured. Veno-occlusive function was
      determined by cavernosography. MAIN OUTCOME MEASURES: The main outcome measures
      of this study were the in vitro and in vivo assessment of cavernosal
      vasoreactivity, veno-occlusive function and erection in mice deficient in
      elastin. RESULTS: Eln (+/-) mice exhibited ~33% less penile elastin than Wt mice,
      with no change in collagen. Cavernosal tissue from Eln(+/-) mice has a
      significantly heightened contractile response, explained in part by increased
      smooth muscle cell content. Veno-occlusive function was significantly altered in
      Eln(+/-) mice. Interestingly, erectile function was impaired only at submaximal
      voltage (1 V) stimulation (there was no impairment during the higher 2-V
      stimulus). CONCLUSIONS: Eln (+/-) mice display a cavernosal phenotype consistent
      with developmental changes attributable to the loss of elastin. These alterations
      confer a degree of altered erectile function that is able to be overridden by
      maximal stimulatory input. Altogether, these data suggest that elastin is
      important for erectile function.

PMID- 21883954
TI  - Time to onset of action of vardenafil: a retrospective analysis of the pivotal
      trials for the orodispersible and film-coated tablet formulations.
AB  - INTRODUCTION: Patients and physicians consider a rapid onset of action to be an
      important attribute of oral pharmacotherapy for erectile dysfunction. AIM: To
      investigate the time to onset of action of a new orodispersible tablet (ODT)
      formulation of vardenafil. METHODS: A post hoc integrated analysis was performed
      on data from two 12-week, double-blind, multicenter, randomized, parallel-group,
      placebo-controlled phase III trials of 10 mg vardenafil ODT. Data for the
      vardenafil film-coated tablet were generated from a retrospective integrated
      analysis at week 12 of four double-blind, multicenter, randomized, parallel
      group, fixed-dose, placebo-controlled phase III trials. Time intervals (in 15-,
      30-, and 60-minute increments, up to >=6 hours after study medication intake)
      were determined for the period between dosing and start of sexual activity (with
      the intention of intercourse). MAIN OUTCOME MEASURES: The total number of sexual
      intercourse attempts and Sexual Encounter Profile question 3 (SEP3) success rates
      were calculated per time interval. RESULTS: Within 15 minutes postdosing, mean
      per-patient SEP3 success rates were 62.5% (vardenafil ODT) vs. 29.4% (placebo),
      with corresponding overall SEP3 success rates of 59.8% and 38.2%. In this time
      interval, 5.3% vs. 2.8% of all sexual activity attempts were initiated by
      subjects taking vardenafil ODT (n = 89) or placebo (n = 62), respectively. At 16
      30 minutes postdosing, SEP3 success rates were 65.3% and 32.6% (mean per-patient)
      and 70.2% and 51.0% (overall) for vardenafil ODT vs. placebo, respectively, with
      a corresponding 10.4% and 8.7% of all sexual activity attempts being made by
      subjects taking vardenafil ODT (n = 170) or placebo (n = 118). Comparable results
      were observed for vardenafil 10 and 20 mg film-coated tablet at corresponding
      time intervals. CONCLUSIONS: Vardenafil ODT shows a rapid onset of action
      comparable with that of vardenafil film-coated tablet. In those men who begin
      sexual activity within 30 minutes after dosing, the majority of sexual attempts
      lead to successful intercourse.

PMID- 21883955
TI  - Synthesis and comparison of antioxidant properties of indole-based melatonin
      analogue indole amino Acid derivatives.
AB  - Increased levels of reactive oxygen species attributed to oxidative stress have
      been found to be responsible for the development of some vital diseases such as
      cardiovascular, neurodegenerative and autoimmune diseases. Recently, it was
      observed that melatonin is a highly important antioxidant, and melatonin
      analogues are under investigation to find out improved antioxidant activity. In
      this study, 14 melatonin -based analogue indole amino acid and N-protected amino
      acid derivatives were synthesized and elucidated spectrometrically. To
      investigate the antioxidant activity of the synthesized compounds and to compare
      with melatonin, butylhydroxytoluene and vitamin E, lipid peroxidation inhibition
      and 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activities were tested. The
      results indicated that the synthesized new indole amino acid derivatives have
      similar activities to melatonin in 2,2-diphenyl-1-picrylhydrazyl radical
      scavenging activity assay but more potent activities in lipid peroxidation
      inhibition assay.

PMID- 21883957
TI  - Synthesis and antibacterial activity of aromatic and heteroaromatic amino
      alcohols.
AB  - Two series of aromatic and heteroaromatic amino alcohols were synthesized from
      alcohols and aldehydes and evaluated for their antibacterial activities. All the
      octylated compounds displayed a better activity against the four bacteria tested
      when evaluated by the agar diffusion method and were selected for the evaluation
      of minimal inhibitory concentration. The best results were obtained for p
      octyloxybenzyl derivatives against Staphylococcus epidermidis (minimal inhibitory
      concentrations = 32 MUm).

PMID- 21883956
TI  - X-ray crystal structure of bone marrow kinase in the x chromosome: a Tec family
      kinase.
AB  - Bone marrow kinase in the X chromosome, a member of the Tec family of tyrosine
      kinases, plays a role in both monocyte/macrophage trafficking as well as cytokine
      secretion. Although the structures of Tec family kinases Bruton's tyrosine kinase
      and IL-2-inducible T-cell kinase are known, the crystal structures of other Tec
      family kinases have remained elusive. We report the X-ray crystal structures of
      bone marrow kinase in the X chromosome in complex with dasatinib at 2.4 A
      resolution and PP2 at 1.9 A resolution. The bone marrow kinase in the X
      chromosome structures reveal a typical kinase protein fold; with well-ordered
      protein conformation that includes an open/extended activation loop and a
      stabilized DFG-motif rendering the kinase in an inactive conformation. Dasatinib
      and PP2 bind to bone marrow kinase in the X chromosome in the ATP binding pocket
      and display similar binding modes to that observed in other Tec and Src protein
      kinases. The bone marrow kinase in the X chromosome structures identify
      conformational elements of the DFG-motif that could potentially be utilized to
      design potent and/or selective bone marrow kinase in the X chromosome inhibitors.

PMID- 21883958
TI  - Effects of hyperoxic ventilation on 6-h survival at the critical haemoglobin
      concentration aggravated by experimentally induced tachycardia in anaesthetized
      pigs.
AB  - AIM: Administration of 100% oxygen [hyperoxic ventilation (HV)] has been proven
      to ameliorate oxygen transport, tissue oxygenation and survival in different
      models of extreme normovolemic and hypovolemic anaemia. However, up to date, it
      is unknown whether HV is also able to improve outcome of extreme anaemia if
      myocardial oxygen consumption is contemporaneously increased by tachycardia.
      Therefore, we investigated the influence of HV on the 6-h survival rate during
      extreme anaemia and aggravated by experimentally induced tachycardia in a
      prospective, randomized study in a pig model of critical anaemia. METHODS: After
      government approval, 14 anesthetized pigs mechanically ventilated on room air
      were haemodiluted by replacing a certain amount of whole blood with hydroxethyl
      starch 6% (200.000/0.5) until their individual critical haemoglobin concentration
      (Hb(crit)) was achieved. At Hb(crit), tachycardia (180 bpm) was induced in all
      animals by atrial pacing. Thereafter, animals were observed for the next 6 h
      either at room air (FiO(2) 0.21; group NOX) or during HV (FiO(2) 1.0; group HOX)
      without further intervention. As primary outcome parameter of this study, the 6-h
      survival rate was selected. RESULTS: Hyperoxic ventilation increased the 6-h
      survival rate from 14 to 100%. In contrast to the NOX group, macrohaemodynamics
      and oxygen transport improved in the HOX group during the observation period
      without apparent adverse effects of HV. CONCLUSIONS: Hyperoxic ventilation can be
      considered a safe and effective measure for the optimization of oxygen supply
      during extreme anaemia and despite concomitant tachycardia within 6 h. Whether HV
      can also be recommended beyond this period warrants further studies.

PMID- 21883959
TI  - Detecting sweet and umami tastes in the gastrointestinal tract.
AB  - Information about nutrients is a critical part of food selection in living
      creatures. Each animal species has developed its own way to safely seek and
      obtain the foods necessary for them to survive and propagate. Necessarily, humans
      and other vertebrates have developed special chemosensory organs such as taste
      and olfactory organs. Much attention, recently, has been given to the
      gastrointestinal (GI) tract as another chemosensory organ. Although the GI tract
      had been considered to be solely for digestion and absorption of foods and
      nutrients, researchers have recently found taste-signalling elements, including
      receptors, in this tissue. Further studies have revealed that taste cells in the
      oral cavity and taste-like cells in the GI tract appear to share common
      characteristics. Major receptors to detect umami, sweet and bitter are found in
      the GI tract, and it is now proposed that taste-like cells reside in the GI tract
      to sense nutrients and help maintain homeostasis. In this review, we summarize
      recent findings of chemoreception especially through sweet and umami sensors in
      the GI tract. In addition, the possibility of purinergic transmission from taste
      like cells in the GI tract to vagus nerves is discussed.

PMID- 21883960
TI  - The effect of continuous and interval exercise on PGC-1alpha and PDK4 mRNA in
      type I and type II fibres of human skeletal muscle.
AB  - AIM: Differences in fibre-type recruitment during exercise may induce a
      heterogenic response in fibre-type gene expression. We have investigated the
      effect of two different exercise protocols on the fibre-type-specific expression
      of master genes involved in oxidative metabolism [proliferator-activated receptor
      gamma coactivator-1alpha (PGC-1alpha) and Pyruvate dehydrogenase kinase 4
      (PDK4)]. METHODS: Untrained subjects (n = 7) completed 90-min cycling either at a
      constant intensity [continuous exercise (CE): approximately 60% of VO(2max) ] or
      as interval exercise (IE: approximately 120/20% VO(2max) , duty cycle 12/18s).
      Muscle samples were taken before (pre) and 3 h after (post) exercise. Single
      fibres were isolated from freeze-dried muscle and characterized as type I or type
      II. The cDNA from two fibres of the same type was pooled and mRNA analysed with
      reverse transcription quantitative real-time PCR. RESULTS: Continuous exercise
      and IE elicited a small increase in blood lactate (<2.5 mM) and moderate glycogen
      depletion (<40%) without difference between exercise modes. The mRNA of PGC
      1alpha and PDK4 increased 5- to 8-fold in both fibre types after exercise, and
      the relative increase was negatively correlated with the basal level. However,
      the mRNA of PGC-1alpha and PDK4 was not different between type I and II fibres
      neither pre nor post, and there was no difference in the exercise-induced
      response between fibre types or exercise modes. CONCLUSION: We conclude that the
      mRNA of PGC-1alpha and PDK4 increases markedly in both fibre types after
      prolonged exercise without difference between CE and IE. The similar response
      between fibre types may relate to that subjects were sedentary and that the
      metabolic stress was low.

PMID- 21883961
TI  - The importance of an extended preoperative trial of BAHA in unilateral
      sensorineural hearing loss: a prospective cohort study.
AB  - OBJECTIVES: The influence of an extended preoperative trial of bone-anchored
      hearing aid (BAHA) and headband on the decision to proceed with surgery in cases
      of unilateral sensorineural hearing loss is studied. DESIGN: In this prospective
      study, the headband was introduced after assessment confirmed suitable candidacy.
      Those who had an initially favourable response to the headband trial were
      encouraged to complete a 2-week home trial of device and headband. Patients were
      asked to pay special attention to situations where they perceived high demands on
      their hearing, e.g. at the dinner table, in the car, walking outside etc.
      Counselling regarding the BAHA placement, the need for daily care of the implant
      site and the financial implications of acquiring the device was also given.
      SETTING: Tertiary university hospital. PARTICIPANTS: Patients with unilateral
      sensorineural hearing loss, fulfilling criteria for BAHA surgery, with favourable
      response to initial 'office trial' of headband. MAIN OUTCOME MEASURES: After 2
      week home trial, BAHA and headband were returned with a statement of the
      patient's intentions. RESULTS: Sixteen of 50 (32%) patients who expressed
      definite interest in BAHA surgery after a positive introduction to the headband
      in the office did not wish to proceed to surgery having completed a more thorough
      2-week trial of device at home. Most patients cited a failure of the device to
      meet their hearing requirements. Subsequently, we found further attrition with
      nine more patients (18%) deciding at a still later date, not to proceed with
      surgery. Ultimately, just 25 of 50 (50%) of our initially enthusiastic group
      chose not to proceed to surgery. In the group who did proceed, there were no non
      users. CONCLUSIONS: We propose the importance of an extended preoperative trial
      where BAHA is considered in the rehabilitation of unilateral sensorineural
      hearing loss. The trial may foster more realistic expectations of device
      performance in this challenging group. A 'cooling-off' period before surgery also
      appears to lead to further attrition with the ultimate reward of no non-users in
      those proceeding to surgery.

PMID- 21883962
TI  - Influenza disease burden in adults by subtypes following the initial epidemic of
      pandemic H1N1 in Singapore.
AB  - Peaks of influenza activity in July 2009 and January 2010 were >90% pandemic H1N1
      (pH1N1), but by May 2010, H3N2 predominated in hospital attendances (46.5%,
      versus 38.9% pH1N1); H3N2 hospital attendances were older (72.9% aged >=60 years
      versus 13.5% for pH1N1), but the age-stratified proportions admitted for
      pneumonia ]were similar. As at the end of the third epidemic wave in Singapore,
      pH1N1 cases in hospital attendances were still markedly younger than cases of
      H3N2 or influenza B, with little evidence for any changes in severity.

PMID- 21883963
TI  - Contribution of murine innate serum inhibitors toward interference within
      influenza virus immune assays.
AB  - BACKGROUND: Prior to detection of an antibody response toward influenza viruses
      using the hemagglutination inhibition assay (HAI), sera are routinely treated to
      inactivate innate inhibitors using both heat inactivation (56 degrees C) and
      recombinant neuraminidase [receptor-destroying enzyme (RDE)]. OBJECTIVES: We
      revisited the contributions of innate serum inhibitors toward interference with
      influenza viruses in immune assays, using murine sera, with emphasis on the
      interactions with influenza A viruses of the H3N2 subtype. METHODS: We used
      individual serum treatments: 56 degrees C alone, RDE alone, or RDE + 56 degrees
      C, to treat sera prior to evaluation within HAI, microneutralization, and
      macrophage uptake assays. RESULTS: Our data demonstrate that inhibitors present
      within untreated murine sera interfere with the HAI assay in a manner that is
      different from that seen for the microneutralization assay. Specifically, the
      gamma class inhibitor alpha(2) -Macroglobulin (A2-M) can inhibit H3N2 viruses
      within the HAI assay, but not in the microneutralization assay. Based on these
      findings, we used a macrophage uptake assay to demonstrate that these inhibitors
      can increase uptake by macrophages when the influenza viruses express an HA from
      a 1968 H3N2 virus isolate, but not a 1997 H3N2 isolate. CONCLUSIONS: The practice
      of treating sera to inactivate innate inhibitors of influenza viruses prior to
      evaluation within immune assays has allowed us to effectively detect influenza
      virus-specific antibodies for decades. However, this practice has yielded an
      under-appreciation for the contribution of innate serum inhibitors toward host
      immune responses against these viruses, including contributions toward
      neutralization and macrophage uptake.

PMID- 21883965
TI  - A novel test tube method of screening for hemoglobin E.
AB  - INTRODUCTION: Hemoglobin (Hb) E is a beta-structural variant common worldwide.
      This Hb disorder can form a compound heterozygous state with the beta-thalassemia
      gene, leading to life-threatening hereditary hemolytic anemia, HbE/beta
      thalassemia. Screening of HbE has proven to be a challenging practice in
      prevention and control of the HbE/beta-thalassemia. METHODS: A novel test tube
      method for HbE screening using diethyl aminoethyl (DEAE)-cellulose resin was
      described. With the developed system, HbE/A(2) did not bind to the resin and
      remained dissolved in the supernatant, whereas other Hbs completely bound to the
      resin. The red color of the supernatant observed in the test tube indicated the
      presence of HbE. Colorless or markedly pale color of the supernatant indicates
      the absence of HbE. RESULTS: Accuracy and efficiency of the established method in
      detecting HbE was comparable with the standard cellulose acetate electrophoresis
      method. The developed method is cheap and simple with no requirement of
      sophisticated equipment. The reagent could be stored at 4  degrees C for up to 5
      months. Hemolysate samples aged up to 5 months were still suitable for this test.
      CONCLUSION: The described novel test tube method could be an alternative method
      of mass population screening for HbE, particularly in small health care
      facilities.

PMID- 21883964
TI  - Performance of rapid influenza H1N1 diagnostic tests: a meta-analysis.
AB  - BACKGROUND: Following the outbreaks of 2009 pandemic H1N1 infection, rapid
      influenza diagnostic tests have been used to detect H1N1 infection. However, no
      meta-analysis has been undertaken to assess the diagnostic accuracy when this
      manuscript was drafted. METHODS: The literature was systematically searched to
      identify studies that reported the performance of rapid tests. Random effects
      meta-analyses were conducted to summarize the overall performance. RESULTS:
      Seventeen studies were selected with 1879 cases and 3477 non-cases. The overall
      sensitivity and specificity estimates of the rapid tests were 0.51 (95%CI: 0.41,
      0.60) and 0.98 (95%CI: 0.94, 0.99). Studies reported heterogeneous sensitivity
      estimates, ranging from 0.11 to 0.88. If the prevalence was 30%, the overall
      positive and negative predictive values were 0.94 (95%CI: 0.85, 0.98) and 0.82
      (95%CI: 0.79, 0.85). The overall specificities from different manufacturers were
      comparable, while there were some differences for the overall sensitivity
      estimates. BinaxNOW had a lower overall sensitivity of 0.39 (95%CI: 0.24, 0.57)
      compared with all the others (P-value <0.001), whereas QuickVue had a higher
      overall sensitivity of 0.57 (95%CI: 0.50, 0.63) compared with all the others (P
      value = 0.005). CONCLUSIONS: Rapid tests have high specificity but low
      sensitivity and thus limited usefulness.

PMID- 21883966
TI  - The role of molecular genetic analysis within the diagnostic haemato-oncology
      laboratory.
AB  - The identification of the molecular genetic basis to many haematological
      malignancies along with the increased use of molecularly targeted therapy has
      heralded an increasing role for molecular genetic-based techniques. Demonstration
      of acquired changes such as the JAK2 V617F mutation within myeloproliferative
      neoplasms has quickly moved from a research setting to the diagnostic laboratory.
      Disease-specific genetic markers, such as the BCR-ABL1 fusion gene in chronic
      myeloid leukaemia, enable sensitive molecular genetic methods to be applied for
      the detection and quantification of low-level residual disease, allowing early
      identification of relapse. Consequently, molecular genetics now plays a crucial
      role in diagnosis, the identification of prognostic markers and monitoring of
      haematological malignancies. The development of high-throughput whole-genome
      approaches offers the potential to rapidly screen newly diagnosed patients for
      all disease-associated molecular genetic changes.

PMID- 21883967
TI  - State of the art in myeloid sarcoma.
AB  - INTRODUCTION: Myeloid sarcomas are extramedullary lesions composed of myeloid
      lineage blasts that typically form tumorous masses and may precede, follow, or
      occur in the absence of systemic acute myeloid leukemia. They most commonly
      involve the skin and soft tissues, lymph nodes, and gastrointestinal tract and
      are particularly challenging to diagnose in patients without an antecedent
      history of acute myeloid leukemia. METHODS: We conducted a search of the English
      language medical literature for recent studies of interest to individuals
      involved in the diagnosis of myeloid sarcoma. RESULTS: The differential diagnosis
      includes non-Hodgkin lymphoma, blastic plasmacytoid dendritic cell neoplasm,
      histiocytic sarcoma, melanoma, carcinoma, and (in children) small round blue cell
      tumors. The sensitivity and specificity of immunohistochemical markers must be
      considered when evaluating a suspected case of myeloid sarcoma. A high percentage
      of tested cases have cytogenetic abnormalities. CONCLUSION: A minimal panel of
      immunohistochemical markers should include anti-CD43 or anti-lysozyme as a lack
      of immunoreactivity for either of these sensitive markers would be inconsistent
      with a diagnosis of myeloid sarcoma. Use of more specific markers of myeloid
      disease, such as CD33, myeloperoxidase, CD34 and CD117 is necessary to establish
      the diagnosis. Other antibodies may be added depending on the differential
      diagnosis. Identification of acute myeloid leukemia-associated genetic lesions
      may be helpful in arriving at the correct diagnosis.

PMID- 21883968
TI  - The use of the white cell count and haemoglobin in combination as an effective
      screen to predict the normality of the full blood count.
AB  - INTRODUCTION: The utility of the full blood count (FBC) is vast with each
      parameter serving as a tool to aid diagnosis and monitor disease progression.
      However, the effectiveness of the test is hampered because of increased workload
      and lack of interpretation. In the effort to redress this issue, the combined use
      of the white blood cell count (WBC) and haemoglobin in predicting the normality
      of the FBC is evaluated. METHOD: FBC data were collated from 2191 patients and
      classified into two groups depending on whether the WBC and the haemoglobin were
      within the reference range. Blood films were examined on the abnormal FBC samples
      in each group and graded on morphology. RESULTS: The FBC was normal in 89.6% of
      cases in the presence of a normal WBC and haemoglobin with subtle abnormalities
      in the remainder; 1+ grading of abnormal morphology in 93%. However, when the WBC
      and/or haemoglobin was abnormal, the remaining FBC was significantly abnormal (P
      < 0.05) and the corresponding blood films were grossly abnormal; 2+/3+ grading in
      96% of cases. CONCLUSION: We concluded that in the presence of a normal WBC and
      haemoglobin, the FBC is normal in almost all cases and measuring these two
      parameters could be used as an effective screen to predict FBC normality.

PMID- 21883969
TI  - Plasma protein oxidation is correlated positively with plasma iron levels and
      negatively with hemolysate zinc levels in sickle-cell anemia patients.
AB  - INTRODUCTION: Sickle-cell anemia (SCA) is a disease of high oxidative stress. The
      oxidative medium of SCA was evaluated by protein oxidation parameters and their
      correlation with lipids and ions were investigated both in the plasma and in the
      erythrocyte. METHODS: Blood samples were obtained from 15 steady-state patients
      with SCA, 10 carriers, and 10 controls. Plasma protein carbonyl, total
      sulfhydryl, total cholesterol, triglyceride, phospholipids, and bilirubin levels
      were determined by spectrophotometric methods. Plasma copper, zinc, and iron
      levels were determined by atomic absorption spectrophotometry. Levels of
      cholesterol, triglyceride, and ions were also determined in the hemolysate lipid
      extract. RESULTS: Patients had increased protein carbonyl and decreased total
      sulfhydryl levels compared with controls. Plasma cholesterol levels were lower
      than controls, and triglyceride levels were higher than carriers in patients with
      SCA. Plasma iron and hemolysate copper were higher in patients than carriers and
      controls. Plasma protein carbonyl levels were found to be correlated with plasma
      iron and hemolysate zinc levels in the patient group. CONCLUSION: Alterations of
      proteins, lipids, and ions in the plasma and erythrocyte of steady-state patients
      with SCA were demonstrated. Some of these alterations are related with each other
      and with the oxidative stress observed in the disease.

PMID- 21883970
TI  - Quantification of hemoglobin Constant Spring in heterozygote and homozygote by a
      capillary electrophoresis method.
AB  - INTRODUCTION: Capillary electrophoresis (CE) is a high-resolution method for
      detection of hemoglobin Constant Spring (Hb CS). METHODS: The levels of Hb CS
      quantified by CE were compared among three groups of samples including
      heterozygote and homozygote of Hb CS as well as Hb H-CS disease classified by DNA
      molecular diagnosis. The mean corpuscular volume (MCV) of red blood cells was
      also analyzed among these three groups. RESULTS: Mean +/- SD of Hb CS level of
      the homozygote was not significantly different from that of the Hb H-CS disease
      (1.9 +/- 1.8 vs. 2.8 +/- 1.3, P = 0.13), but it was significantly higher than
      that of the heterozygote (1.9 +/- 1.8 vs. 0.4 +/- 0.2, P = 0.007). The MCV <70 fL
      was found in Hb H-CS disease only. CONCLUSION: CE is the preferable method for
      screening of heterozygote and homozygote of Hb CS. Moreover, in conjunction with
      a lower MCV (<70 fL), this approach provided a high resolution to identify Hb H
      CS disease.

PMID- 21883971
TI  - Suicidal changes in patients with first episode psychosis: clinical predictors of
      increasing suicidal tendency in the early treatment phase.
AB  - AIM: To identify predictors for developing a higher suicidal tendency during
      treatment of first-episode psychosis. METHODS: In a prospective follow-up study,
      we examined clinical factors collected at treatment initiation as predictors for
      developing a higher suicidal tendency among patients in the first year of
      treatment of psychosis. Patients were grouped and ranked according to their
      highest suicidal tendency in the year before treatment: not suicidal, suicidal
      thoughts, suicidal plans or suicide attempt(s). Predictors for becoming more
      suicidal in the first year of treatment were examined on group level in
      multivariate logistic regression analyses. We assessed patients' suicidal
      tendency and clinical factors using validated interviews and rating scales.
      Analysis included 386 patients. RESULTS: Among patients with some suicidal
      tendency a one-point increase score on hallucinations significantly predicted
      developing a higher suicidal tendency, whereas a one-point increase score on
      delusions was preventive of this. Feeling hopeless was highly associated with
      suicide attempt in those with earlier suicide attempt. CONCLUSION: The risk of
      suicide attempt did not differ between patient groups with suicidal thoughts,
      plans or suicide attempt. In first year of treatment of psychosis, hallucinations
      increased the risk for becoming more suicidal, whereas delusions reduced this
      risk in already suicidal patients.

PMID- 21883972
TI  - Prodromal psychosis screening in adolescent psychiatry clinics.
AB  - BACKGROUND: Research has identified a syndrome conferring ultra-high risk (UHR)
      for psychosis, although UHR interviews require intensive staff training, time and
      patient burden. Previously, we developed the Prodromal Questionnaire (PQ) to
      screen more efficiently for UHR syndromes. AIMS: This study examined the
      concurrent validity of the PQ against UHR status and preliminary predictive
      validity for later psychotic disorder. METHOD: We assessed a consecutive patient
      sample of 408 adolescents who presented to psychiatry clinics in Helsinki,
      Finland, seeking mental health treatment, including 80 participants who completed
      the Structured Interview for Prodromal Syndromes (SIPS). RESULTS: A cut-off score
      of 18 or more positive symptoms on the PQ predicted UHR diagnoses on the SIPS
      with 82% sensitivity and 49% specificity. Three of 14 (21%) participants with
      high PQ scores and SIPS UHR diagnoses developed full psychotic disorders within 1
      year. CONCLUSIONS: Using the PQ and SIPS together can be an efficient two-stage
      screening process for prodromal psychosis in mental health clinics.

PMID- 21883973
TI  - Children's experiences of parental mental illness: a literature review.
AB  - AIM: This paper provides a review of published qualitative research on children's
      experiences of parental mental illness. METHODS: We undertook a comprehensive
      search of Medical Literature Analysis and Retrieval System Online, PsycINFO,
      Cumulative Index to Nursing and Allied Health Literature, Sociological Abstracts
      and Applied Social Sciences Index and Abstracts databases, as well as citation
      searches in Web of Science and manual searches of other relevant journals and
      reference lists of primary papers. RESULTS: Although 20 studies met the search
      criteria, only 10 focused exclusively on children's descriptions of their
      experience--the remainder elicited adults' perspectives on children's experiences
      of parental mental illnesses. Findings are organized under three themes: the
      impact of illness on children's daily life, how children cope with their
      experiences and how children understand mental illness. CONCLUSIONS: Despite
      references to pervasive knowledge gaps in the literature, significant information
      has been accumulated about children's experiences of parental mental illness.
      Considerable variability in research findings and tensions remain unresolved. For
      example, evidence is mixed as to children's knowledge and understanding of mental
      illnesses and how best to deploy resources to help them acquire optimal
      information. Furthermore, children's desire to be recognized as important to
      their parents' well-being conflicted with adults' perceptions that children
      should be protected from too much responsibility. Nevertheless, the cumulative
      evidence remains a key reason for advocating for psychoeducation and peer-support
      group interventions for children, which are endorsed by child and adult study
      participants alike.

PMID- 21883974
TI  - Non-expert clinicians' detection of autistic traits among attenders of a youth
      mental health service.
AB  - AIMS: The aims of this study were to determine the point prevalence of autism
      spectrum disorders and to estimate the prevalence of autistic traits in a youth
      mental health service. METHODS: Following three educational sessions on autism
      spectrum disorders, treating clinicians were interviewed to determine whether the
      clients on their caseloads had (i) a confirmed prior diagnosis of autism spectrum
      disorder; (ii) were felt to exhibit autistic traits; or (iii) were not felt to
      exhibit autistic traits. RESULTS: Information on autism spectrum disorder status
      was obtained for 476 patients. Of the included patients, 3.4% (n = 16) had a
      confirmed diagnosis of autism spectrum disorder and 7.8% (n = 37) were reported
      by treating clinicians to exhibit autistic traits. CONCLUSIONS: The rate of
      autism spectrum disorder was higher in this population than that in community
      samples with twice as many again being identified as having autistic traits by
      their treating clinicians. This has implications for correct diagnosis and
      appropriate management in these settings.

PMID- 21883975
TI  - Growth phase-associated changes in the proteome and transcriptome of
      Lactobacillus rhamnosus GG in industrial-type whey medium.
AB  - The growth phase during which probiotic bacteria are harvested and consumed can
      strongly influence their performance as health-promoting agents. In this study,
      global transcriptomic and proteomic changes were studied in the widely used
      probiotic Lactobacillus rhamnosus GG during growth in industrial-type whey medium
      under strictly defined bioreactor conditions. The expression of 636 genes (P <=
      0.01) and 116 proteins (P < 0.05) changed significantly over time. Of the
      significantly differentially produced proteins, 61 were associated with
      alterations at the transcript level. The most remarkable growth phase-dependent
      changes occurred during the transition from the exponential to the stationary
      growth phase and were associated with the shift from glucose fermentation to
      galactose utilization and the transition from homolactic to mixed acid
      fermentation. Furthermore, several genes encoding proteins proposed to promote
      the survival and persistence of L. rhamnosus GG in the host and proteins that
      directly contribute to human health showed temporal changes in expression. Our
      results suggest that L. rhamnosus GG has a highly flexible and adaptable
      metabolism and that the growth stage during which bacterial cells are harvested
      and consumed should be taken into consideration to gain the maximal benefit from
      probiotic bacteria.

PMID- 21883977
TI  - Intramuscular injection of soluble receptor for advanced glycation endproducts
      expression vector prevents the development of streptozotocin-induced diabetes
      mellitus in rats on high fat diet.
AB  - BACKGROUND: In order to study if advanced glycation endproducts (AGE) in high
      temperature cooked high fat diet could be the cause of type 2 diabetes, a
      expressing vector encoding soluble form of receptor for AGE (sRAGE) was injected
      intramuscularly, and the incidence of streptozotocin (STZ)-induced diabetes
      mellitus in rats on high fat diet were observed. METHODS: Rat sRAGE gene, cloned
      to a pLNCX(2) expression vector (pLNCX(2) -sRAGE), was injected into the hind leg
      muscles of Sprague-Dawley rats. Rats were fed with high fat diet for 8 weeks
      before pLNCX(2) -sRAGE injection (designed as T group), or pLNCX2 (as H group),
      and rats on normal chow (as N group). The diet remained the same until end of the
      study. Serum malondialdehyde (MDA) and superoxide dismutase (SOD) levels were
      studied in one serial of rats (n = 8) under the treatment of different vectors
      without STZ injection. For a second serial of study (n = 20), rats were injected
      with 30 mg/kg STZ intraperitoneally 2 weeks after the second injection of
      vectors, and tail blood glucose was detected 1 week later. RESULTS:
      Malondialdehyde levels were found to be decreased 1 week after injection of sRAGE
      and lasted for at least 3 weeks after each injection. SOD activities were found
      to be increased slowly in the second week after each injection. As determined
      with fasting and random glycemia only two rats were in diabetic level (fasting
      glycemia >=7.0 mmol/L and random glycemia >=11.1 mmol/L) in T group while eight
      mice were in the diabetic level in H group. CONCLUSIONS: Intramuscular injection
      of sRAGE decreases the MDA level and increases SOD activities, and decreases the
      STZ-induced incidence of diabetes in rats in high fat diet.

PMID- 21883978
TI  - Emotional distress is associated with poor self care in type 2 diabetes mellitus.
AB  - BACKGROUND: The aim of the present study was to evaluate possible clinical and
      psychosocial variables that influence diabetes self-care management in patients
      with type 2 diabetes mellitus (T2DM). METHODS: A total of 150 individuals with
      T2DM who had had diabetes for at least 6 months were recruited to this cross
      sectional study. Levels of self-care and psychosocial status were determined
      using the Self-Care Inventory (SCI) and Problem Areas in Diabetes (PAID) scale.
      The PAID scores were calculated using a five-point Likert scale with options
      ranging from 0 (not a problem) to 4 (serious problem). Data were evaluated using
      non-parametric and parametric tests as appropriate. RESULTS: The mean age of the
      study participants was 69.97 +/- 8.68 years. Cronbach's alpha for SCI and PAID
      scores was 0.85 and 0.98, respectively. People with poor glycemic control had
      significantly higher mean (+/-SD) total PAID scores than individuals with good
      glycemic control (29.5 +/- 30.9 vs 16.7 +/- 26.9, respectively; P = 0.012). There
      was a significant relationship between PAID scores and glycemic control (r = 0.2;
      P = 0.012). CONCLUSIONS: The present study demonstrates that psychosocial factors
      directly influence glycemic control and diabetes self-care habits. In addition,
      diabetes-specific distress in study population was unrelated to the duration of
      diabetes, the age of the patients and anthropometric indices.

PMID- 21883976
TI  - Strategies for discovery and improvement of enzyme function: state of the art and
      opportunities.
AB  - Developments in biocatalysis have been largely fuelled by consumer demands for
      new products, industrial attempts to improving existing process and minimizing
      waste, coupled with governmental measures to regulate consumer safety along with
      scientific advancements. One of the major hurdles to application of biocatalysis
      to chemical synthesis is unavailability of the desired enzyme to catalyse the
      reaction to allow for a viable process development. Even when the desired enzyme
      is available it often forces the process engineers to alter process parameters
      due to inadequacies of the enzyme, such as instability, inhibition, low yield or
      selectivity, etc. Developments in the field of enzyme or reaction engineering
      have allowed access to means to achieve the ends, such as directed evolution, de
      novo protein design, use of non-conventional media, using new substrates for old
      enzymes, active-site imprinting, altering temperature, etc. Utilization of enzyme
      discovery and improvement tools therefore provides a feasible means to overcome
      this problem. Judicious employment of these tools has resulted in significant
      advancements that have leveraged the research from laboratory to market thus
      impacting economic growth; however, there are further opportunities that have not
      yet been explored. The present review attempts to highlight some of these
      achievements and potential opportunities.

PMID- 21883979
TI  - DNA barcoding meets molecular scatology: short mtDNA sequences for standardized
      species assignment of carnivore noninvasive samples.
AB  - Although species assignment of scats is important to study carnivore biology,
      there is still no standardized assay for the identification of carnivores
      worldwide, which would allow large-scale routine assessments and reliable cross
      comparison of results. Here, we evaluate the potential of two short mtDNA
      fragments [ATP6 (126 bp) and cytochrome oxidase I gene (COI) (187 bp)] to serve
      as standard markers for the Carnivora. Samples of 66 species were sequenced for
      one or both of these segments. Alignments were complemented with archival
      sequences and analysed with three approaches (tree-based, distance-based and
      character-based). Intraspecific genetic distances were generally lower than
      between-species distances, resulting in diagnosable clusters for 86% (ATP6) and
      85% (COI) of the species. Notable exceptions were recently diverged species, most
      of which could still be identified using diagnostic characters and uniqueness of
      haplotypes or by reducing the geographic scope of the comparison. In silico
      analyses were also performed for a 110-bp cytochrome b (cytb) segment, whose
      identification success was lower (70%), possibly due to the smaller number of
      informative sites and/or the influence of misidentified sequences obtained from
      GenBank. Finally, we performed case studies with faecal samples, which supported
      the suitability of our two focal markers for poor-quality DNA and allowed an
      assessment of prey DNA co-amplification. No evidence of prey DNA contamination
      was found for ATP6, while some cases were observed for COI and subsequently
      eliminated by the design of more specific primers. Overall, our results indicate
      that these segments hold good potential as standard markers for accurate species
      level identification in the Carnivora.

PMID- 21883980
TI  - A new version of PRT software for sibling groups reconstruction with comments
      regarding several issues in the sibling reconstruction problem.
AB  - Pedigree reconstruction using genotypic markers has become an important tool for
      the study of natural populations. The nonstandard nature of the underlying
      statistical problems has led to the necessity of developing specialized
      statistical and computational methods. In this article, a new version of pedigree
      reconstruction tools (PRT 2.0) is presented. The software implements algorithms
      proposed in Almudevar & Field (Journal of Agricultural Biological and
      Environmental Statistics, 4, 1999, 136) and Almudevar (Biometrics, 57, 2001a,
      757) for the reconstruction of single generation sibling groups (SG). A wider
      range of enumeration algorithms is included, permitting improved computational
      performance. In particular, an iterative version of the algorithm designed for
      larger samples is included in a fully automated form. The new version also
      includes expanded simulation utilities, as well as extensive reporting, including
      half-sibling compatibility, parental genotype estimates and flagging of potential
      genotype errors. A number of alternative algorithms are described and
      demonstrated. A comparative discussion of the underlying methodologies is
      presented. Although important aspects of this problem remain open, we argue that
      a number of methodologies including maximum likelihood estimation (COLONY 1.2 and
      2.0) and the set cover formulation (KINALYZER) exhibit undesirable properties in
      the sibling reconstruction problem. There is considerable evidence that large
      sets of individuals not genetically excluded as siblings can be inferred to be a
      true sibling group, but it is also true that unrelated individuals may be
      genetically compatible with a true sibling group by chance. Such individuals may
      be identified on a statistical basis. PRT 2.0, based on these sound statistical
      principles, is able to efficiently match or exceed the highest reported accuracy
      rates, particularly for larger SG. The new version is available at
      http://www.urmc.rochester.edu/biostat/people/faculty/almudevar.cfm.

PMID- 21883981
TI  - Nonspecific PCR amplification by high-fidelity polymerases: implications for next
      generation sequencing of AFLP markers.
AB  - High-fidelity 'proofreading' polymerases are often used in library construction
      for next-generation sequencing projects, in an effort to minimize errors in the
      resulting sequence data. The increased template fidelity of these polymerases can
      come at the cost of reduced template specificity, and library preparation methods
      based on the AFLP technique may be particularly susceptible. Here, we compare
      AFLP profiles generated with standard Taq and two versions of a high-fidelity
      polymerase. We find that Taq produces fewer and brighter peaks than high-fidelity
      polymerase, suggesting that Taq performs better at selectively amplifying
      templates that exactly match the primer sequences. Because the higher accuracy of
      proofreading polymerases remains important for sequencing applications, we
      suggest that it may be more effective to use alternative library preparation
      methods.

PMID- 21883982
TI  - Cellular and clinical report of new Griscelli syndrome type III cases.
AB  - The RAB27A/Melanophilin/Myosin-5a tripartite protein complex is required for
      capturing mature melanosomes in the peripheral actin network of melanocytes for
      subsequent transfer to keratinocytes. Mutations in any one member of this
      tripartite complex cause three forms of Griscelli syndrome (GS), each with
      distinct clinical features but with a similar cellular phenotype. To date, only
      one case of GS type III (GSIII), caused by mutations in the Melanophilin (MLPH)
      gene, has been reported. Here, we report seven new cases of GSIII in three
      distinct Arab pedigrees. All affected individuals carried a homozygous missense
      mutation (c.102C>T; p.R35W), located in the conserved Slp homology domain of
      MLPH, and had hypomelanosis of the skin and hair. We report the first cellular
      studies on GSIII melanocytes, which demonstrated that MLPH(R35W) causes
      perinuclear aggregation of melanosomes in melanocytes, typical for GS.
      Additionally, co-immunoprecipitation assays showed that MLPH(R35W) lost its
      interaction with RAB27A, indicating pathogenicity of the R35W mutation.

PMID- 21883983
TI  - Identification of a melanocyte-specific, microphthalmia-associated transcription
      factor-dependent regulatory element in the intronic duplication causing hair
      greying and melanoma in horses.
AB  - Greying with age in horses is an autosomal dominant trait, characterized by hair
      greying, high incidence of melanoma and vitiligo-like depigmentation. Previous
      studies have revealed that the causative mutation for this phenotype is a 4.6-kb
      intronic duplication in STX17 (Syntaxin 17). By using reporter constructs in
      transgenic zebrafish, we show that a construct containing two copies of the
      duplicated sequence acts as a strong enhancer in neural crest cells and has
      subsequent melanophore-specific activity during zebrafish embryonic development
      whereas a single copy of the duplicated sequence acts as a weak enhancer,
      consistent with the phenotypic manifestation of the mutation in horses. We
      further used luciferase assays to investigate regulatory regions in the
      duplication, to reveal tissue-specific activities of these elements. One region
      upregulated the reporter gene expression in a melanocyte-specific manner and
      contained two microphthalmia-associated transcription factor (MITF) binding
      sites, essential for the activity. Microphthalmia-associated transcription factor
      regulates melanocyte development, and these binding sites are outstanding
      candidates for mediating the melanocyte-specific activity of the element. These
      results provide strong support for the causative nature of the duplication and
      constitute an explanation for the melanocyte-specific effects of the Grey allele.

PMID- 21883984
TI  - Two separate Ni(2+) -sensitive voltage-gated Ca(2+) channels modulate
      transretinal signalling in the isolated murine retina.
AB  - PURPOSE: Light-evoked responses from vertebrate retinas were recorded as an
      electroretinogram (ERG). The b-wave is the most prominent component of the ERG,
      and in the bovine retina its NiCl(2) -sensitive component was attributed to
      reciprocal signalling by pharmacoresistant R-type voltage-gated Ca(2+) channels,
      which similar to other voltage-dependent Ca(2+) channels trigger and control
      neurotransmitter release. The murine retina has the great advantage that the
      effect of gene inactivation for Ni(2+) -sensitive Ca(2+) channels can be analysed
      to prove or disprove that any of these Ca(2+) channels is involved in retinal
      signalling. METHODS: Superfused retinas from different murine genotypes lacking
      either one or both highly Ni(2+) -sensitive voltage-gated Ca(2+) channels were
      used to record their ex vivo ERGs. RESULTS: The isolated retinas from mice
      lacking Ca(v)2.3 R-type or Ca(v)3.2 T-type or both voltage-gated Ca(2+) channels
      were superfused with a NiCl(2) (15 MUm) containing nutrient solution. The change
      in the b-wave amplitude and implicit time, caused by NiCl(2), was calculated as a
      difference spectrum and compared to data from control animals. From the results,
      it can be deduced that Ca(v)2.3 contributes rather to a later component in the b
      wave response, while in the absence of Ca(v)3.2 the gain of Ni(2+) -mediated
      increase in the b-wave amplitude is significantly increased, probably due to a
      loss of reciprocal inhibition to photoreceptors. Thus, each of the Ni(2+)
      sensitive Ca(2+) channels contributes to specific features of the b-wave
      response. CONCLUSION: Both high-affinity Ni(2+)-sensitive Ca(2+) channels
      contribute to transretinal signalling. Based on the results from the double
      knockout mice, additional targets for NiCl(2) must contribute to transretinal
      signalling, which will be most important for the structurally similar
      physiologically more important heavy metal cation Zn(2+).

PMID- 21883985
TI  - Two-year follow-up of a randomized trial of spectacles alone or combined with
      Bangerter filters for treating anisometropic amblyopia.
AB  - PURPOSE: To compare spectacle correction alone to spectacle correction with
      Bangerter filters as treatments for anisometropic amblyopia in children 1 year
      after completion of a 1-year randomized trial. METHODS: In a randomized clinical
      trial, 80 children (mean age, 4.4 years) with anisometropic amblyopia and a best
      median visual acuity (VA) in the amblyopic eye of 0.4 logarithm of the minimum
      angle of resolution (logMAR) were assigned to treatment with either spectacles or
      spectacles in combination with a Bangerter filter for 1 year. After 1 year,
      treatment with spectacles continued. If the VA differed by >= 2 lines, treatment
      with Bangerter filters was continued if originally prescribed. The main outcome
      measure was the median change in VA of the amblyopic eye after 2 years. RESULTS:
      The median change in VA of the amblyopic eye did not differ significantly between
      the groups (0.4 log unit for both groups) at the 2-year visit. At that time, the
      VA in the amblyopic eyes and the fellow eyes was 0.0 median logMAR in both
      groups. Between years 1 and 2, the median VA improved in the amblyopic eyes; in
      the spectacles group (p = 0.0181) and in the Bangerter filter group (p = 0.0342).
      The median anisometropia decreased in both groups (p < 0.0001 for both
      comparisons). CONCLUSION: We found stability in the VA improvement in both
      groups. The magnitude of the VA change 2 years after treatment with spectacles
      alone did not differ significantly from that after treatment with spectacles and
      a Bangerter filter for anisometropic amblyopia.

PMID- 21883986
TI  - The post-illumination pupil response of melanopsin-expressing intrinsically
      photosensitive retinal ganglion cells in diabetes.
AB  - PURPOSE: This study investigates the clinical utility of the melanopsin
      expressing intrinsically photosensitive retinal ganglion cell (ipRGC) controlled
      post-illumination pupil response (PIPR) as a novel technique for documenting
      inner retinal function in patients with Type II diabetes without diabetic
      retinopathy. METHODS: The PIPR was measured in seven patients with Type II
      diabetes, normal retinal nerve fibre thickness and no diabetic retinopathy
      compared to healthy age-similar controls. A 488- and 610-nm, 7.15-diameter
      stimulus was presented in Maxwellian view to the right eye and the left
      consensual pupil light reflex was recorded. RESULTS: The group data for the blue
      PIPR (488 nm) identified a trend of reduced ipRGC function in patients with
      diabetes with no retinopathy. The transient pupil constriction was lower on
      average in the diabetic group. The relationship between duration of diabetes and
      the blue PIPR amplitude was linear, suggesting that ipRGC function decreases with
      increasing diabetes duration. CONCLUSION: This is the first report to show that
      the ipRGC-controlled PIPR may have clinical applications as a non-invasive
      technique for determining the progression of inner neuroretinal changes in
      patients with diabetes before they are ophthalmoscopically or anatomically
      evident. The lower transient pupil constriction amplitude indicates that outer
      retinal photoreceptor inputs to the pupil light reflex may also be affected in
      diabetes.

PMID- 21883987
TI  - In vivo evaluation of photoreceptor mosaic in early onset large colloid drusen
      using adaptive optics.

PMID- 21883988
TI  - Prevalence and incidence of ocular trauma in North China: the Beijing Eye Study.
AB  - PURPOSE: To determine the prevalence and incidence of ocular trauma and
      proportion of trauma-related visual impairment in the population of Greater
      Beijing. METHODS: The population-based Beijing Eye Study included 4439 subjects
      in 2001, of whom 3251 subjects returned for follow-up examination in 2006
      (response rate: 73.3%). The subjects underwent a comprehensive ocular evaluation.
      Prospective information on ocular trauma and type of treatment was recorded with
      questionnaires in face-to-face interviews. RESULTS: A history of ocular trauma
      was reported by 72 (1.6 +/- 0.2%) subjects (age-standardized prevalence: 1.7 +/-
      0.01%). Prevalence of ocular trauma history was associated with male gender (p =
      0.02), rural residence (p = 0.04) and alcohol consumption (p = 0.01). Trauma as
      underlying cause for visual impairment (best-corrected visual acuity < 20/60 and
      >= 20/400) was found in 4 (6.6%) eyes and as underlying cause for blindness (best
      corrected visual acuity <20/400) in three eyes (4.2%). In the survey of 2006, 116
      (3.6 +/- 0.3%) participants had a self-reported history of ocular trauma, which
      was associated with male gender (p = 0.002), low income (p = 0.01) and alcohol
      consumption (p = 0.016). The 5-year incidence of ocular trauma was 2.6 +/- 0.3%,
      which was associated with male gender (p = 0.02), younger age (p = 0.037) and
      lower income (p = 0.009). CONCLUSIONS: In the adult population of Greater Beijing
      with an age of 40+ years, the prevalence of ocular trauma was 1.6 +/- 0.2% and
      was associated with male gender, rural residence and alcohol consumption. The age
      standardized ocular trauma prevalence of 1.7 +/- 0.01% was comparable with
      figures from Caucasian populations. The 5-year incidence of ocular trauma of 2.6
      +/- 0.3% was associated with male gender, younger age and lower income.

PMID- 21883989
TI  - Circulating antiretinal antibodies predict the outcome of anti-VEGF therapy in
      patients with exudative age-related macular degeneration.
AB  - PURPOSE: To determine serum antiretinal antibody (ARA) levels in response to
      treatment with intravitreal bevacizumab of exudative age-related macular
      degeneration (AMD). METHODS: The study comprised 22 patients treated with
      intravitreal bevacizumab (Avastin) 1.25mg. In all patients, serum ARA levels were
      assessed by indirect immunofluorescence on normal monkey retina substrate. The
      ophthalmic examination including best corrected visual acuity (BCVA), fundoscopy,
      fluorescein angiography, optical coherence tomography (OCT) and
      immunohistochemical investigations. These were repeated at 4-week intervals
      during a loading phase of antiangiogenic therapy. Sera of 22 sex- and age-matched
      healthy subjects were used as controls for immunohistochemical studies. RESULTS:
      Before bevacizumab therapy, ARAs were detected in the sera of all patients at
      titres ranging from 1:40 to 1:1280. The titres were significantly higher (p <
      0.01) than in controls (1:10-1:40). There was no significant correlation between
      serum ARA titres and neither the type nor the dimensions of choroidal
      neovascularization, as well as central retinal thickness. Following treatment,
      all patients demonstrated significant decrease in ARA levels. This correlated
      with improvement of BCVA, decreased leakage of fluorescein and reduction of
      subretinal fluid on OCT. CONCLUSION: Serum ARA levels demonstrate a dynamic
      change which occurs in parallel with clinical outcomes of antiangiogenic therapy.
      They also may act as markers of the therapeutic benefits of vascular endothelial
      growth factor inhibition.

PMID- 21883990
TI  - Clopidogrel resistance: identifying and overcoming a barrier to effective
      antiplatelet treatment.
AB  - Clopidogrel is an inhibitor of the ADP receptor P2Y12 and platelet aggregation.
      It is widely used for the management of atherothrombotic disease in patients who
      have experienced severe vascular events such as stroke or myocardial infarction
      or with peripheral artery disease. However, some patients show "resistance" to
      clopidogrel, and show impaired inhibition of platelet aggregation. In this
      review, I discuss the clinical evidence of the extent of the problem, potential
      implications for future cardiovascular events and clinical tests to assess
      platelet aggregation. I also discuss the mechanisms that appear responsible for
      clopidogrel resistance. Clopidogrel is administered as a prodrug and the active
      metabolite is generated by the cytochrome P450 system. Therefore, inadequate
      responses to clopidogrel may be caused by polymorphisms in one or more of the
      cytochrome P450 enzymes and interaction/competition with other drugs metabolized
      by the cytochrome P450 system (e.g., statins and proton pump inhibitors).
      Finally, I discuss the therapeutic options available for patients with known or
      suspected clopidogrel resistance, including the use of drugs with alternative
      molecular targets (e.g., cilostazol), metabolized via different pathways (e.g.,
      prasugrel) or administered in an active form (e.g., ticagrelor). Clopidogrel
      resistance is a clinically significant problem with potentially severe
      consequences if it is not identified or managed appropriately. The availability
      of point-of-care assays and novel treatments provide clinicians with an extensive
      array of tools that should aid in the management of atherothrombotic
      diseases/events, and reduce the risk of future severe events in these patients.

PMID- 21883991
TI  - Targeting fibrosis for the treatment of heart failure: a role for transforming
      growth factor-beta.
AB  - Chronic heart failure (CHF) is a growing health problem in developed nations. The
      pathological accumulation of extracellular matrix is a key contributor to CHF in
      both diabetic and nondiabetic states, resulting in progressive stiffening of the
      ventricular walls and loss of contractility. Proinflammatory disease processes,
      including inflammatory cytokine activation, contribute to accumulation of
      extracellular matrix in the heart. Transforming growth factor-beta is a key
      profibrotic cytokine mediating fibrosis. Current therapeutic strategies do not
      directly target the profibrotic inflammatory processes occurring in the heart and
      hence there is a clear unmet clinical need to develop new therapeutic agents
      targeting fibrosis. Accordingly, strategies that inhibit proinflammatory cytokine
      activation and pathological accumulation of extracellular matrix (ECM) provide a
      potential therapeutic target for prevention of heart failure. This review focuses
      on the therapeutic targeting of TGF-beta in the prevention of pathological
      fibrosis in the heart.

PMID- 21883992
TI  - Interventional treatments for hypertrophic cardiomyopathy.
AB  - Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder.
      This autosomal dominant condition is defined by left ventricular hypertrophy and
      associated with functional limitation and premature death. In fact, many
      individuals are asymptomatic and the annual mortality in most modern series is 1%
      or less. However, severe symptoms may develop at any age, and the risk of
      premature death from arrhythmia, stroke, and progressive systolic impairment may
      complicate asymptomatic disease. The clinical management of patients with HCM
      therefore encompasses (1) genetic counseling including discussion of indications
      for genetic testing and cascade family screening, (2) assessment of prognostic
      risk from ventricular arrhythmia, stroke, and heart failure, and (3) symptom
      management. This article describes the interventional treatments in the
      management of severe symptoms associated with left ventricular outflow tract
      obstruction (LVOTO).

PMID- 21883993
TI  - Two coronary "orphan" diseases in search of clinical consideration: coronary
      syndromes x and y.
AB  - We set out to describe the clinical characteristics of patients presenting with
      acute or stable coronary syndromes and no stenosis in epicardial coronaries.
      Although the existence of patients who experience typical angina and who have
      intact epicardial coronaries is well accepted, the pathophysiology of cardiac
      ischemia in this setting remains poorly understood. In typical coronary syndrome
      X, it is believed that at least two components play a role: the first is the
      incapacity of coronary resistance vessels to adapt to situations of increased
      blood demand, resulting in demand ischemia; the second is an inappropriate
      transduction or generation or pain stimuli within the central nervous system.
      These two mechanisms concur to determine episodes of precordial pain and
      electrocardiogram (ECG) evidence of ischemia during exercise. In contrast, the
      coronary slow-flow phenomenon, or syndrome Y, is an angiographic finding that is
      characterized by delayed progression of the contrast medium during coronary
      angiography. Although the mechanism of this phenomenon remains largely unknown,
      it has been proposed that it might depend on the presence of inappropriately high
      resting coronary resistances, causing reduced blood flow and therefore low-flow
      ischemia and unstable angina. Importantly, the prognosis of many of the patients
      presenting with coronary slow-flow does not appear to be favorable, with
      recurrence of acute coronary syndromes and life-threatening arrhythmias. In the
      present article, we revise the current evidence regarding these two phenomena,
      and propose that syndrome Y should be considered a separate clinical entity.

PMID- 21883994
TI  - Patent foramen ovale--assessment and treatment.
AB  - A patent foramen ovale (PFO) is detectable in 20-25% of the population. Some, but
      not all, case control studies have found an increased incidence of PFO in
      patients with cryptogenic stroke. Prospective cohort studies have failed to
      convincingly demonstrate a link between PFO and first stroke, and evidence
      linking PFO to recurrent stroke is far from compelling. The rate of recurrent
      stroke in medically treated patients is low, but the development of devices for
      PFO closure has lead to enthusiasm in some quarters to pursue a strategy of
      device closure. Nonrandomized studies have suggested a lower risk of recurrent
      events with device closure but the data are heterogeneous, and potentially prone
      to bias. Device implantation is associated with a risk of major adverse events of
      between 1.5% and 2.3%, and there is a significant rate of failure to close
      shunts. The results of randomized trials of device closure are keenly awaited.
      Migraine with aura has been linked with PFO. A recent metanalysis suggested an
      association, but the one prospective population study did not. The well
      publicized and controversial MIST Trial is the only randomized trial of device
      closure in migraineurs yet published, and failed to demonstrate a convincing
      benefit from device closure. Other conditions such as platypnea-orthodeoxia
      syndrome and prevention of decompression sickness in divers, may justify device
      closure. Evidence for a role of PFO in the etiology of cryptogenic stroke and
      migraine is contradictory. It is possible that some patients might benefit from
      PFO closure but there is scant evidence of sufficient quality to justify routine
      PFO closure in either group. It is essential that ongoing randomized trials of
      device closure are completed.

PMID- 21883995
TI  - Hyperkalemia associated with use of angiotensin-converting enzyme inhibitors and
      angiotensin receptor blockers.
AB  - The aims of this article are to review the current understanding of hyperkalemia
      associated with angiotensin-converting enzyme inhibitor (ACEi) or angiotensin
      receptor blocker (ARB) therapy. This includes reviewing the pathophysiology of
      how these agents affect potassium handling within the kidney, risk factors for
      developing hyperkalemia, incidence, clinical signs and symptoms, and providing a
      practical approach to treatment of the patient who is either at risk of, or
      experiencing, hyperkalemia. ACEi and ARB are effective therapeutic agents used in
      a variety of clinical scenarios. However, related to their effects on the renin
      angiotensin-aldosterone system, their use can be associated with hyperkalemia,
      particularly in patients who have chronic renal insufficiency. Published
      incidence estimates of hyperkalemia associated with ACEi or ARB vary, but up to
      10% of patients may experience at least mild hyperkalemia. Important
      considerations when initiating ACEi or ARB therapy include obtaining an estimate
      of glomerular filtration rate and a baseline serum potassium concentration, as
      well as assessing whether the patient has excessive potassium intake from diet,
      supplements, or drugs that can also increase serum potassium. Serum potassium
      monitoring shortly after initiation of therapy can assist in preventing
      hyperkalemia. If hyperkalemia does develop, prompt recognition of cardiac
      dysrhythmias and effective treatment to antagonize the cardiac effects of
      potassium, redistribute potassium into cells, and remove excess potassium from
      the body is important.Understanding the mechanism of action of ACEi and ARB
      coupled with judicious drug use and clinical vigilance can minimize the risk to
      the patient of developing hyperkalemia. Should hyperkalemia occur, prompt
      recognition and management can optimize clinical outcome.

PMID- 21883996
TI  - Microembolic signals and aspirin resistance in patients with carotid stenosis.
AB  - INTRODUCTION AND AIMS: Aspirin resistance may be linked to increased risk of
      cardiovascular events. We aimed to evaluate whether it was associated with
      presence of microembolic signals (MES), a readily measurable marker of increased
      stroke risk, in those with internal carotid artery (ICA) disease. METHODS: We
      studied patients with significant ICA disease who were compliant with aspirin
      therapy. We performed monitoring for MES and measured aspirin resistance status,
      using the platelet function analyzer (PFA)-100 and Verify-Now systems. We
      compared frequency of aspirin resistance between patients with and without MES
      and assessed agreement between the different platelet function tests. RESULTS: We
      recruited 62 patients. Most (53, 85.5%) had symptomatic carotid disease and 16
      (25.8%) had MES. The rate of aspirin resistance on at least one test was 25.8%
      (16 patients), with 13 (21%) resistant on PFA-100 testing, 8 (12.9%) using the
      Verify-Now system and 5 (8.1%) resistant on both. Aspirin resistance was more
      common in patients with MES (50% compared to 17.4% without, P= 0.018 on Fisher's
      exact test). Agreement between the platelet function tests was moderate (k=
      0.41). CONCLUSION: Aspirin resistance appears more common in patients with
      carotid disease who have MES compared to those without. Further work should aim
      to establish whether screening for aspirin resistance and subsequent adjustment
      to antiplatelet therapy reduces the rate of MES and stroke risk in those with
      carotid disease.

PMID- 21883997
TI  - Effects of beta-blockade on exercise performance at high altitude: a randomized,
      placebo-controlled trial comparing the efficacy of nebivolol versus carvedilol in
      healthy subjects.
AB  - AIMS: Exposure to high altitude (HA) hypoxia decreases exercise performance in
      healthy subjects. Although beta-blockers are known to affect exercise capacity in
      normoxia, no data are available comparing selective and nonselective beta
      adrenergic blockade on exercise performance in healthy subjects acutely exposed
      to HA hypoxia. We compared the impact of nebivolol and carvedilol on exercise
      capacity in healthy subjects acutely exposed to HA hypobaric hypoxia. METHODS: In
      this double-blind, placebo-controlled trial, 27 healthy untrained sea-level (SL)
      residents (15 males, age 38.3 +/- 12.8 years) were randomized to placebo (n = 9),
      carvedilol 25 mg b.i.d. (n = 9), or nebivolol 5 mg o.d. (n = 9). Primary
      endpoints were measures of exercise performance evaluated by cardiopulmonary
      exercise testing at sea level without treatment, and after at least 3 weeks of
      treatment, both at SL and shortly after arrival at HA (4559 m). RESULTS: HA
      hypoxia significantly decreased resting and peak oxygen saturation, peak
      workload, VO(2) , and heart rate (HR) (P < 0.01). Changes from SL (no treatment)
      differed among treatments: (1) peak VO(2)  was better preserved with nebivolol (
      22.5%) than with carvedilol (-37.6%) (P < 0.01); (2) peak HR decreased with
      carvedilol (-43.9 +/- 11.9 beats/min) more than with nebivolol (-24.8 +/- 13.6
      beats/min) (P < 0.05); (3) peak minute ventilation (VE) decreased with carvedilol
      (-9.3%) and increased with nebivolol (+15.2%) (P= 0.053). Only peak VE changes
      independently predicted changes in peak VO(2)  at multivariate analysis (R= 0.62,
      P < 0.01). CONCLUSIONS: Exercise performance is better preserved with nebivolol
      than with carvedilol under acute exposure to HA hypoxia in healthy subjects.

PMID- 21883998
TI  - Novel platelet ADP P2Y12 inhibitors in the treatment of acute coronary syndrome.
AB  - Inhibition of the platelet P2Y12 receptor plays an important role in the
      prevention of thrombotic complications of acute coronary syndrome and
      percutaneous coronary interventions. Despite clinical benefits with clopidogrel
      therapy in these high risk patients, efficacy of clopidogrel is limited by slow
      onset of action, variability in platelet inhibitory response and potential drug
      drug interactions. Importantly, suboptimal platelet inhibition by clopidogrel is
      associated with worse prognosis. This underscores the need for alternate
      antiplatelet treatment strategies. A number of novel P2Y12 antagonists are
      approved or in advanced development and some have demonstrated superior platelet
      inhibition effect, clinical outcomes, and safety profile than clopidogrel in
      patients with acute coronary syndrome. The aim of this manuscript is to provide
      an overview on the current status in P2Y12 receptor inhibition and to review the
      pharmacology and clinical development of four of these agents: prasugrel,
      cangrelor, ticagrelor, and elinogrel.

PMID- 21884000
TI  - Serum levels of advanced glycation end products (AGEs) are inversely associated
      with the number and migratory activity of circulating endothelial progenitor
      cells in apparently healthy subjects.
AB  - OBJECTIVES: Endothelial progenitor cells (EPCs) have been shown to participate in
      the process of vascular repair, thus playing a protective role against
      cardiovascular disease (CVD). It is known that atherosclerotic risk factors could
      affect EPC number and function. Advanced glycation end products (AGEs) contribute
      to the pathogenesis of atherosclerosis as well. However, as far as we know, there
      is no report to show the relationship between serum AGE levels and circulating
      EPCs in humans. Therefore, in this study, we investigated whether serum level of
      AGEs was associated with EPC number and functions in apparently healthy subjects,
      independent of traditional cardiovascular risk factors. RESEARCH DESIGN AND
      METHODS: Apparently healthy volunteers (34.6 +/- 6.9 years old, 40 males and 8
      females) who were not on any medications underwent a complete history and
      physical examination, determination of blood chemistries, including AGEs, and
      number, differentiation and migratory activity of circulating EPCs. RESULTS:
      Serum AGEs levels were 9.20 +/- 1.85 U/mL. Multiple stepwise regression analysis
      revealed that serum levels of AGEs and smoking were independently correlated with
      reduced number of EPCs. Further, female, AGEs, and reduced HDL-cholesterol levels
      were independently associated with impaired migratory activity of circulating
      EPCs. CONCLUSIONS: This study demonstrated for the first time that the serum
      level of AGEs was one of the independent correlates of decreased cell number and
      impaired migratory activity of circulating EPCs in apparently healthy subjects.
      Our present observations suggest that even in young healthy subjects, serum level
      of AGEs may be a biomarker that could predict the progression of atherosclerosis
      and future cardiovascular events.

PMID- 21883999
TI  - TRITON and beyond: new insights into the profile of prasugrel.
AB  - Prasugrel, a third-generation thienopyridine antiplatelet agent, demonstrated
      superior efficacy to clopidogrel but with an increased risk of bleeding in the
      phase III pivotal registration Trial to Assess Improvement in Therapeutic
      Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in
      Myocardial Infarction (TRITON-TIMI 38). This article reviews and discusses select
      components of a large literature of prasugrel data that has emerged since the
      TRITON-TIMI 38 (TRITON) study primary disclosure.

PMID- 21884001
TI  - Why do homocysteine-lowering B vitamin and antioxidant E vitamin supplementations
      appear to be ineffective in the prevention of cardiovascular diseases?
AB  - Homocysteine has been established as a serious, independent risk factor for
      atherosclerosis. An elevated plasma homocysteine concentration is accompanied by
      increased cardiovascular risk; therefore, it can be assumed that lowering the
      plasma homocysteine level results in a decreased risk. Vitamin B complex (folic
      acid, and vitamins B6 and B12) substitution therapy decreases the plasma
      homocysteine level, inhibits oxidative stress, and ameliorates some biochemical
      and clinical parameters that indicate the progression of atherosclerosis. Vitamin
      E administration may also reduce atherogenesis through its antioxidant effect.
      The effectiveness of B and E vitamin substitution in decreasing cardiovascular
      risk has been suggested by cohort as well as prospective and retrospective
      studies undertaken during the last two decades. On the other hand, recent large,
      randomized clinical trials did not substantiate a beneficial effect of
      homocysteine-lowering B vitamin supplementation or vitamin E antioxidant
      therapies in reducing cardiovascular risk in humans. We analyzed eight B vitamin
      and four E vitamin trials from a critical point of view, and in this article we
      reviewed and commented on their results and focused on the contradictions found
      in them. We showed that the possible factors implicated in the failure of vitamin
      therapies included inappropriate designs. The protocols neglected an essential
      fact: that the impact of some confounding factors, such as concomitant use of
      statins, acetylsalicylic acid, folic acid, and other drugs, might have led to
      bias and an inappropriate interpretation of the data. The cardiovascular
      protective and preventive effects of statins and aspirin might have reduced or
      abolished the possibility of observing a difference in the number of events
      between the vitamin and placebo groups for the clinical endpoints. We concluded
      that the vitamin preventive effect on cardiovascular disease may not be rejected
      in reference to the negative trial evidence.

PMID- 21884002
TI  - Statin myopathy: a lipid clinic experience on the tolerability of statin
      rechallenge.
AB  - INTRODUCTION: Statin myopathy is a generally encountered side effect of statin
      usage. Both muscle symptoms and a raised serum creatine kinase (CK) are used in
      case definition, but these are common manifestations of other conditions, which
      may not be statin related. Statin rechallenge assuming no contraindication in
      selected cases is an option before considering a different class of lipid
      lowering agent. AIMS: We aim to characterize retrospectively the patients
      referred to our Lipid Clinic with a diagnosis of statin myopathy. The
      tolerability of different statins was assessed to determine a strategy for
      rechallenging statins in such patients in the future. RESULTS: Patients with
      statin myopathy constitute 10.2% of our Lipid Clinic workload. They are
      predominantly female (62.0%), Caucasian (63.9%), with a mean age of 58.3 years
      and mean body mass index (BMI) of 29.3 kg/m(2). The serum CK and erythrocyte
      sedimentation rate (ESR) were statistically higher compared to patients with
      statin intolerances with no muscular component or CK elevations. Secondary causes
      of statin myopathy were implicated in 2.7% of cases. Following statin myopathy to
      simvastatin we found no statistical difference between the tolerability rates
      between atorvastatin, rosuvastatin, pravastatin, and fluvastatin. Fibrates,
      cholestyramine, and ezetimibe were statistically better tolerated in these
      patients. CONCLUSIONS: Statin rechallenge is a real treatment option in patients
      with statin myopathy. Detailed history and examination is required to exclude
      muscle diseases unrelated to statin usage. In patients developing statin myopathy
      on simvastatin, we did not find any statistical difference between subsequent
      tolerability rates to rosuvastatin, pravastatin, and fluvastatin.

PMID- 21884003
TI  - Pharmacological properties of the central antihypertensive agent, moxonidine.
AB  - The sympathetic nervous system plays a central role in the pathophysiology not
      only of hypertension and other cardiovascular diseases but also metabolic
      disorders including disturbances of glucose and lipid homeostasis. A centrally
      acting sympathetic agent is therefore attractive not only for lowering blood
      pressure, but also intervening with multiple disease processes. Older agents such
      as clonidine and guanabenz have numerous side effects, including sedation and dry
      mouth that limit their acceptability to patients. Moxonidine and the related
      agent rilmenidine have greatly reduced side effects, because they have reduced
      activity at the alpha(2) -adrenergic receptors that mediate these undesirable
      actions. Instead, moxonidine and rilmenidine act primarily through a novel
      cellular site, termed the I(1) -imidazoline receptor. The molecular biology of
      the I(1) -imidazoline receptor protein has recently been described, and the cell
      signaling pathways linked to this protein have been characterized. Moxonidine has
      unique effects on a number of cell types through this unusual cellular site of
      action. There are multiple therapeutic implications of these cellular actions,
      especially for metabolic syndrome and its associated derangements in glucose and
      lipid metabolism. Finally, the clinical trials that seemed to identify an
      unfavorable outcome in severe heart failure are dissected and critiqued. We
      conclude that moxonidine and future successors to this agent could be of great
      value in treating multiple chronic diseases.

PMID- 21884004
TI  - Imidazoline antihypertensive drugs: selective i(1) -imidazoline receptors
      activation.
AB  - Involvement of imidazoline receptors (IR) in the regulation of vasomotor tone as
      well as in the mechanism of action of some centrally acting antihypertensives has
      received tremendous attention. To date, pharmacological studies have allowed the
      characterization of three main imidazoline receptor classes, the I(1) 
      imidazoline receptor which is involved in central inhibition of sympathetic tone
      to lower blood pressure, the I(2) -imidazoline receptor which is an allosteric
      binding site of monoamine oxidase B (MAO-B), and the I(3) -imidazoline receptor
      which regulates insulin secretion from pancreatic beta-cells. All three
      imidazoline receptors represent important targets for cardiovascular research.
      The hypotensive effect of clonidine-like centrally acting antihypertensives was
      attributed both to alpha(2) -adrenergic receptors and nonadrenergic I(1) 
      imidazoline receptors, whereas their sedative action involves activation of only
      alpha(2) -adrenergic receptors located in the locus coeruleus. Since more
      selective I(1) -imidazoline receptors ligands reduced incidence of typical side
      effects of other centrally acting antihypertensives, there is significant
      interest in developing new agents with higher selectivity and affinity for I(1) 
      imidazoline receptors. The selective imidazoline receptors agents are also more
      effective in regulation of body fat, neuroprotection, inflammation, cell
      proliferation, epilepsy, depression, stress, cell adhesion, and pain. New
      agonists and antagonists with high selectivity for imidazoline receptor subtypes
      have been recently developed. In the present review we provide a brief update to
      the field of imidazoline research, highlighting some of the chemical diversity
      and progress made in the theoretical studies of imidazoline receptor ligands.

PMID- 21884005
TI  - Overexpression of vasostatin-1 protects hypoxia/reoxygenation injuries in
      cardiomyocytes independent of endothelial cells.
AB  - INTRODUCTION: Vasostatin-1 (VS-1) has been suggested in protecting
      hypoxia/reoxygenation (H/R) injuries in isolated hearts. However, the molecular
      mechanisms remained to be elucidated. METHODS: Cardiomyocytes were treated with
      recombinant Ad-VS-1 adenoviral vector before H/R. Cell viability was studied
      using MTT methods and annexin V-FITC flow cytometry. Intracellular oxidative
      stress was measured by superoxide dismutase (SOD) and malondialdehyde (MDA), and
      inflammatory reactions by enzyme-linked immunosorbent assay (ELISA). Measurement
      of myocardial nitrous oxide synthase (NOS) was determined by serum nitric oxide
      (NO) concentrations using nitrite reductase and endothelial nitric oxide synthase
      (eNOS) by Western blotting. Inhibitors of the NOS system, including hemoglobin
      and KT5823, were applied to verify the results. RESULTS: In comparison of the
      blank group, cardiac myocytes overexpressing VS-1 showed significant decrease in
      apoptosis, intracellular oxidative stress, and inflammatory reactions (P < 0.05).
      In addition, serum NO concentrations and expression of eNOS were notably enhanced
      (P < 0.05). These protective effects of VS-1 were suppressed in the presence of
      apoptosis-inducing agents. CONCLUSIONS: Overexpression of VS-1 in cardiomyocytes
      could limit the H/R injuries at molecular levels. The protective effects were
      independent of endothelial cell function, suggestive of a potential therapeutic
      target for patients with myocardial ischemia in the future.

PMID- 21884006
TI  - Ginsenoside Re: pharmacological effects on cardiovascular system.
AB  - Ginsenosides are the bioactive constituents of ginseng, a key herb in traditional
      Chinese medicine. As a single component of ginseng, ginsenoside Re (G-Re) belongs
      to the panaxatriol group. Many reports demonstrated that G-Re possesses the
      multifaceted beneficial pharmacological effects on cardiovascular system. G-Re
      has negative effect on cardiac contractility and autorhythmicity. It causes
      alternations in cardiac electrophysiological properties, which may account for
      its antiarrhythmic effect. In addition, G-Re also exerts antiischemic effect and
      induces angiogenic regeneration. In this review, we first outline the chemistry
      and the pharmacological effects of G-Re on the cardiovascular system.

PMID- 21884007
TI  - Additive effect of homocysteine- and cholesterol-lowering therapy on endothelium
      dependent vasodilation in patients with cardiovascular disease.
AB  - AIM: Endothelial dysfunction is a marker for development and progression of
      atherosclerosis. Statin therapy improves endothelial function in cardiovascular
      patients by reducing LDL-cholesterol and by pleiotropic effects. B-group vitamin
      supplementation restores endothelial function mainly by reducing homocysteine
      induced oxidative stress. Thus, we evaluated the effect of rosuvastatin, B-group
      vitamins and their combination on endothelial function in high-risk
      cardiovascular patients. METHODS: Thirty-six patients with cardiovascular disease
      were randomly, double-blinded assigned to either rosuvastatin 10 mg (group R, n =
      18) or vitamin supplementation consisting of folic acid 1 mg, vitamin B12 0.4 mg,
      and B6 10 mg (group V, n = 18) for 6 weeks. After 6 weeks all patients received
      rosuvastatin and vitamin supplementation in combination for additional 6 weeks.
      Endothelial function was assessed by flow-mediated vasodilation (FMD) at baseline
      and after 6- and 12-week treatment. RESULTS: At baseline, FMD, plasma lipids,
      vitamins, and homocysteine were comparable between both groups. After 6 weeks,
      FMD improved in both groups (from 4.4 +/- 1.6 to 6.9 +/- 1.4% group R, P= 0.0004
      and from 4.9 +/- 1.8 to 6.4 +/- 1.8% group V, P= 0.0002). This improvement in FMD
      was mainly associated with a decrease of plasma lipids in group R and a decrease
      of homocysteine in group V. After 12 weeks, the combined therapy with
      rosuvastatin and vitamins further improved FMD to the normal range in 26/33
      patients compared to 5/36 at baseline (P < 0.0001). CONCLUSIONS: In conclusion,
      both treatments, rosuvastatin and B-group vitamin supplementation, improved
      endothelial function in high-risk cardiovascular patients. The combination of
      both therapies had an additive effect on endothelial function suggesting
      different mechanisms of action.

PMID- 21884008
TI  - Metabolic antianginal agent ranolazine offers good symptom relief in a patient
      with inoperable severe aortic stenosis.
AB  - Severe inoperable aortic stenosis is a challenge for clinicians. Management of
      symptoms with traditional antianginal agents, which exert hemodynamic changes
      often may not be possible in such patient groups. We report the first known case
      of the safe use of ranolazine with good symptomatic relief of angina in an 88
      year-old lady with isolated severe aortic stenosis (without significant coronary
      disease) who was not suitable for surgical or percutaneous valve replacement due
      to medical comorbidity.

PMID- 21884009
TI  - Targeting inflammation in cardiovascular diseases. still a neglected field?
AB  - Prevention and treatment of atherosclerosis is still a clinical challenge in the
      cardiovascular medicine. The classical belief that atherosclerotic lesion
      development solely depends on lipid deposition has been replaced by the current
      concept that activation of immune and inflammatory responses plays a central role
      in plaque initiation and progression. In this review we summarize studies on
      human and genetically modified animals describing a finite number of cellular and
      molecular mechanisms that underlie immunoinflammation in atherosclerotic plaques.
      We focus on the pro- and antiinflammatory mediators activated during
      atherogenesis and the intracellular signaling pathways regulating these events.
      Besides the advances on established pharmacological agents, we propose potential
      strategies for reduction/stabilization of atherosclerotic plaques based on the
      clinical data in inflammatory-associated pathologies and on the encouraging
      studies in experimental models of atherosclerosis. We emphasize the potential of
      such novel inhibitors comprising receptor antagonists, neutralizing antibodies,
      kinase inhibitors, peptide-based technologies, and chemicals as emerging
      antiinflammatory strategies for the treatment of atherosclerotic disease
      complications.

PMID- 21884010
TI  - Trimetazidine reduces endogenous free fatty acid oxidation and improves
      myocardial efficiency in obese humans.
AB  - INTRODUCTION: The metabolic modulator trimetazidine (TMZ) has been suggested to
      induce a metabolic shift from myocardial fatty acid oxidation (FAO) to glucose
      utilization, but this mechanism remains unproven in humans. The oxidation of
      plasma derived FA is commonly measured in humans, whereas the contribution of FA
      from triglycerides stored in the myocardium has been poorly characterized. AIMS:
      To verify the hypothesis that TMZ induces a metabolic shift, we combined positron
      emission tomography (PET) and magnetic resonance spectroscopy ((1)H-MRS) to
      measure myocardial FAO from plasma and intracellular lipids, and myocardial
      glucose metabolism. Nine obese subjects were studied before and after 1 month of
      TMZ treatment. Myocardial glucose and FA metabolism were assessed by PET with
      (18)F-fluorodeoxyglucose and (11)C-palmitate. (1)H-MRS was used to measure
      myocardial lipids, the latter being integrated into the PET data analysis to
      quantify myocardial triglyceride turnover. RESULTS: Myocardial FAO derived from
      intracellular lipids was at least equal to that of plasma FAs (P = NS). BMI and
      cardiac work were positively associated with the oxidation of plasma derived FA
      (P <= 0.01). TMZ halved total and triglyceride-derived myocardial FAO (32.7 +/-
      8.0 to 19.6 +/- 4.0 MUmol/min and 23.7 +/- 7.5 to 10.3 +/- 2.7 MUmol/min,
      respectively; P <= 0.05). These changes were accompanied by increased cardiac
      efficiency since unchanged LV work (1.6 +/- 0.2 to 1.6 +/- 0.1 Watt/g * 10(2),
      NS) was associated with decreased work energy from the intramyocardial
      triglyceride oxidation (1.6 +/- 0.5 to 0.4 +/- 0.1 Watt/g * 10(2), P = 0.036).
      CONCLUSIONS: In obese subjects, we demonstrate that myocardial intracellular
      triglyceride oxidation significantly provides FA-derived energy for mechanical
      work. TMZ reduced the oxidation of triglyceride-derived myocardial FAs improving
      myocardial efficiency.

PMID- 21884011
TI  - Matricellular proteins: new molecular targets to prevent heart failure.
AB  - Matricellular proteins are highly expressed in reparative responses to pressure
      and volume overload, ischemia, oxidative stress after myocardial injury, and
      modulate the inflammatory and fibrotic process in ventricular remodeling, which
      leads to cardiac dysfunction and eventually overt heart failure. Generally,
      matricellular proteins loosen strong adhesion of cardiomyocytes to extracellular
      matrix, which would help cells to move for rearrangement and allow inflammatory
      cells and capillary vessels to spread during tissue remodeling. Among
      matricellular proteins, osteopontin (OPN) and tenascin-C (TN-C) are de-adhesion
      proteins and upregulate the expression and activity of matrix metalloproteinases.
      These matricellular proteins could be key molecules to diagnose cardiac
      remodeling and also might be targets for the prevention of adverse ventricular
      remodeling. This review provides an overview of the role of matricellular
      proteins such as OPN and TN-C in cardiac function and remodeling, as determined
      by both in basic and in clinical studies.

PMID- 21884012
TI  - Sunitinib, a receptor tyrosine kinase inhibitor, increases blood pressure in rats
      without associated changes in cardiac structure and function.
AB  - BACKGROUND: Sunitinib, a multi-tyrosine kinase inhibitor has demonstrated
      clinical activity in advanced renal cell carcinoma and imatinib
      resistant/intolerant gastrointestinal stromal tumor. It has been associated with
      manageable hypertension and other unique toxicities. AIMS: Two nonclinical
      studies were conducted to determine if sunitinib has direct/indirect effects on
      cardiac structure/function that may be related to hypertension at clinically
      relevant exposures. MATERIALS & METHODS: Rats received once-daily vehicle or
      sunitinib 1 or 10 mg/kg/day (n = 10/group) orally for 4 weeks, followed by 2
      weeks off treatment then a 2-week rechallenge. Blood pressure (BP) and heart rate
      (HR) were continuously acquired and echocardiograms were obtained weekly. Effects
      of sunitinib and its metabolite (0.003-0.3 MUM) were also evaluated in guinea pig
      isolated Langendorff-perfused hearts (n = 4-6 hearts/group). RESULTS: Sunitinib
      10 mg/kg/day produced significant (P < 0.05) hemodynamic changes: 24 h average BP
      increased during initial dosing/rechallenge, with rebound hypotension during the
      off-treatment period; 24 h average HR increased during the off-treatment period,
      and decreased during rechallenge; no changes in cardiac structure/function were
      observed. In guinea pig isolated hearts, neither sunitinib nor its metabolite had
      direct effects on contractility, HR or left ventricular pressure. DISCUSSION &
      CONCLUSION: These studies demonstrate that sunitinib/metabolite had no direct
      effects on cardiac function ex vivo, and that therapeutically relevant
      concentrations of sunitinib dosed on a "clinical schedule" increased BP in rats
      without adverse changes in cardiac structure/function.

PMID- 21884014
TI  - Novel treatments for cardiovascular disease prevention.
AB  - The purpose of this review is to describe novel pharmacologic and
      nonpharmacologic preventive therapies, as well as new strategies to improve
      delivery of available therapies. Cardiovascular disease (CVD) is the leading
      cause of death worldwide, and prevention plays a critical role in curbing the
      global epidemic. Despite available treatment for tobacco addiction, platelet
      inhibition, blood pressure, and lipid lowering for reduction of atherosclerotic
      disease, significant gaps in treatment of total CVD remain. We review a range of
      new preventive treatment options, including drugs for tobacco cessation,
      platelet/thrombotic inhibition, lipid- and blood pressure-lowering;
      nonpharmacologic options such as left atrial appendage closure devices and
      caloric restriction; and strategies such as fixed-dose combination drugs,
      laboratory screening for drug tailoring, and community-based prevention programs.
      CVD preventive research continues to evolve and provide clinicians and patients
      with novel pharmacologic and nonpharmacologic therapies, including new preventive
      strategies.

PMID- 21884015
TI  - The future of anticoagulant therapy.

PMID- 21884013
TI  - ARIES-3: ambrisentan therapy in a diverse population of patients with pulmonary
      hypertension.
AB  - INTRODUCTION: Ambrisentan is an oral, once daily, endothelin receptor antagonist
      approved for treatment of pulmonary arterial hypertension (PAH). Previous studies
      of ambrisentan were limited to patients with Group 1 PAH and often excluded
      patients receiving other pulmonary hypertension (PH) therapies. AIMS: ARIES-3 was
      an open-label study evaluating efficacy and safety of ambrisentan in patients
      with various PH etiologies and background PH medications. Patients received 5 mg
      ambrisentan once daily for 24 weeks. The primary endpoint was change from
      baseline in 6-minute walk distance (6MWD) at week 24. RESULTS: A total of 224
      patients with PH due to idiopathic and familial PAH (31%), connective tissue
      disease (18%), chronic hypoxemia (22%), chronic thromboembolic disease (13%), or
      other etiologies (16%) were enrolled and 53% of patients received stable
      background PAH therapies. After 24 weeks of therapy, an increase in 6MWD (+21 m;
      95% CI: 12-29) and a decrease in B-type natriuretic peptide (-26%; 95% CI: -34 to
      -16%) was observed in the overall population compared to baseline; however,
      increases in 6MWD were not observed in several non-Group 1 PH subpopulations.
      Peripheral edema, headache, and dyspnea were the most common adverse events.
      CONCLUSION: This study reconfirms the results of previous placebo-controlled
      studies, which demonstrate that ambrisentan is well tolerated and provides
      benefit in patients with PAH. Definitive conclusions regarding the safety and
      efficacy of ambrisentan in specific non-Group 1 PH etiologies cannot be
      determined and larger, controlled studies will be necessary to determine the
      efficacy and safety of ambrisentan in these populations.

PMID- 21884016
TI  - Evaluation of the effects of urotensin II and soluble epoxide hydrolase inhibitor
      on skin microvessel tone in healthy controls and heart failure patients.
AB  - INTRODUCTION: Urotensin II (UII) is a potent vasoactive peptide that exerts
      differential effects on heart failure (HF) patients compared to health controls.
      However, the mechanism of action remains unclear. The role of soluble epoxide
      hydrolase (sEH) as a mediator of UII in the vasculature has not been explored.
      AIMS: The aim of this study was to examine the effect of UII in the presence and
      absence of sEH inhibitor AUDA on skin microvessel tone in HF patients and healthy
      controls using iontophoresis and laser Doppler velocimetry. UII (10(-7) M) and
      AUDA (10(-10), 10(-7), and 10(-5) M) were administered to the forearm of
      participants by iontophoresis for 30 seconds. Laser Doppler velocimetry was
      performed for 5 minutes to measure flux through the subcutaneous blood vessels.
      Response (flux) was measured for 5 minutes per concentration with 25 continuous
      scans. RESULTS: UII increased flux in healthy controls by 39% (P < 0.05) and
      increased flux in HF patients by 6% (ns). AUDA (10(-10) and 10(-7) M)
      administration further decreased flux by 115% (P < 0.05) and 255% (P < 0.0001),
      respectively in healthy controls. In HF patients, AUDA (10(-10), 10(-7), and 10(
      5) M) further increased flux by 77% (P < 0.05), 67% (P < 0.01), and 100% (P <
      0.05), respectively. AUDA alone at 10(-7) M increased flux in both groups by 31%
      (healthy controls, P < 0.05) and 36% (HF, P < 0.01). CONCLUSION: Taken together,
      the presence of HF appeared to abrogate the vasodilator responsiveness of sEH
      inhibitor. These results suggest an important role for both UII and sEH in
      vascular regulation and that sEH may be involved in mediating UII effects.
      Furthermore, the study highlights the therapeutic potential of sEH inhibitors for
      the treatment of HF.

PMID- 21884017
TI  - Blood pressure and cardiovascular outcomes in patients taking nonsteroidal
      antiinflammatory drugs.
AB  - INTRODUCTION: The increased thrombotic cardiovascular (CV) risk in trials of
      cyclo-oxygenase-2 (COX-2) inhibitors versus placebo, and the apparent similar
      risk with nonsteroidal antiinflammatory drugs (NSAIDs), may be related to their
      potential to elevate blood pressure (BP). AIMS: We evaluated the relationship
      between baseline BP and change in BP on CV events (CVEs) in patients receiving
      NSAIDs or COX-2 inhibitors in the prospective randomized, double-blind,
      Multinational Etoricoxib and Diclofenac Arthritis Long-term Program (N = 34,701)
      comparing etoricoxib 60 or 90 mg or diclofenac 150 mg daily for a mean duration
      of 18 months. The main outcome measure was confirmed thrombotic CVEs. The
      Antiplatelet Trialists' Collaboration endpoint, all-cause mortality,
      CV/congestive heart failure (CHF) mortality, and CHF incidence were similarly
      evaluated. RESULTS: We found that baseline systolic BP (SBP) was associated with
      significantly higher risk of all events (P < 0.001). Baseline diastolic BP (DBP)
      was inversely and significantly associated with risk of all events (P < 0.001 to
      P = 0.016) except CV/CHF mortality (P = 0.054). There was no significant
      differential effect between etoricoxib and diclofenac in relation to CVEs, except
      for confirmed CHF, for which the risk was significantly higher with etoricoxib (P
      = 0.019). Only CHF risk (P = 0.020 for both SBP and DBP change), but not
      thrombotic endpoints, was significantly associated with change in BP from months
      0 to 4. These findings were not meaningfully altered after covariate adjustment
      for baseline CV risk. CONCLUSIONS: Baseline BP, but not change in BP, was
      significantly associated with risk of thrombotic CVEs through 18 months. The CV
      risk of COX-2s and NSAIDs did not appear to be related to the BP-elevating
      effects of these agents, although such analyses, i.e., from randomized controlled
      trials, are unable to definitively exclude such a relationship.

PMID- 21884018
TI  - Efficacy of a new accelerated streptokinase regime in acute myocardial
      infarction: a double blind randomized clinical trial.
AB  - BACKGROUND: Studies of thrombolysis in acute ST-elevation myocardial infarction
      (STEMI) have focused on differences in outcome between groups receiving various
      regimes. Expedited treatment may influence the efficacy of nonfibrin specific
      thrombolytic agents in restoring early patency of the infarct-related artery
      (IRA), which is a major determinant of survival after ST-elevation myocardial
      infarction (STEMI). METHODS: We performed a randomized double blind clinical
      trial comparing an accelerated infusion (1.5 MU/20 min; group A, n = 200) with
      the conventional infusion (1.5 MU/60 min; group B, n = 100) of streptokinase (SK)
      in 300 patients with their first episode of acute STEMI. Demographics, clinical
      reperfusion rates, angiographic study findings, left ventricular ejection
      fraction (LVEF), in-hospital morbidity and mortality and one year mortality were
      compared between two groups. RESULTS: Mean age was 59 +/- 12 years (79% male).
      There were no differences in baseline data between groups. Clinical,
      electrocardiographic and physiologic reperfusion indices revealed significant
      faster and higher reperfusion rates and better preserved LVEF at discharge in
      group A. Sixty-three percent of patients in either group underwent invasive
      coronary angiography at a mean of 5 days with comparable findings. Atrial
      fibrillation, malignant ventricular arrhythmias in the second day, in-hospital
      and late mortalities rates occurred more frequently in group B patients. In
      multivariate analysis, accelerated SK infusion was the only independent predictor
      of higher electrocardiographic reperfusion (OR = 3.2, CI: 1.93-5.3, P < 0.001).
      CONCLUSIONS: The accelerated SK infusion regimen of 1.5 MU in 20 min is safe and
      well tolerated with significantly faster and higher clinical reperfusion rates,
      more preserved LV systolic function, less atrial and ventricular sustained
      arrhythmias, and less in-hospital and 1 year mortality rates in acute STEMI.

PMID- 21884020
TI  - Thiazide-induced hyponatraemia: epidemiology and clues to pathogenesis.
AB  - Thiazide diuretics are one of the most widely used and cost-effective classes of
      antihypertensive agents worldwide. Thiazides however have a significant side
      effect profile and are frequently insufficient to normalize blood pressure alone.
      Thiazide-induced hyponatraemia (TIH) is a major adverse effect, affecting up to
      one in seven patients receiving these drugs. TIH is more common in females, the
      elderly and those of low body weight and may cause symptoms such as confusion,
      falls and seizures. It is a common cause of hospital admission in the elderly.
      Although TIH occurs at least as frequently as hypokalaemia, much less is
      understood about the mechanism by which this occurs. Thiazides lower blood
      pressure by reducing the reabsorption of sodium from the distal nephron by
      inhibition of the NaCl cotransporter. The molecular mechanism by which this
      occurs together with the little known role of thiazides in regulating water
      reabsorbtion from the collecting ducts is discussed and the relevance to TIH
      evaluated. TIH is highly reproducible by thiazide rechallenge suggesting there
      may be a genetic predisposition. Both targeted resequencing of candidate genes
      and genome wide association techniques offer promising strategies by which such
      genetic contributions may be investigated. The rewards for uncovering the
      molecular mechanisms underlying TIH and the regulation of distal nephron sodium
      and water absorption are significant; not only could it inform the design of
      better tolerated, more efficacious thiazide-like antihypertensive agents but it
      may also facilitate the pharmacogenomic profiling of hypertensive patients to
      avoid thiazides in those likely to suffer adverse effects.

PMID- 21884019
TI  - Pilates in heart failure patients: a randomized controlled pilot trial.
AB  - BACKGROUND: Conventional cardiac rehabilitation program consist of 15 min of warm
      up, 30 min of aerobic exercise and followed by 15 min calisthenics exercise. The
      Pilates method has been increasingly applied for its therapeutic benefits,
      however little scientific evidence supports or rebukes its use as a treatment in
      patients with heart failure (HF). PURPOSE: Investigate the effects of Pilates on
      exercise capacity variables in HF. METHODS: Sixteen pts with HF, left ventricular
      ejection fraction 27 +/- 14%, NYHA class I-II were randomly assigned to
      conventional cardiac rehabilitation program (n = 8) or mat Pilates training (n =
      8) for 16 weeks of 30 min of aerobic exercise followed by 20 min of the specific
      program. RESULTS: At 16 weeks, pts in the mat Pilates group and conventional
      group showed significantly increase on exercise time 11.9 +/- 2.5 to 17.8 +/- 4
      and 11.7 +/- 3.9 to 14.2 +/- 4 min, respectively. However, only the Pilates group
      increased significantly the ventilation (from 56 +/- 20 to 69 +/- 17 L/min, P =
      0.02), peak VO(2) (from 20.9 +/- 6 to 24.8 +/- 6 mL/kg/min, P = 0.01), and O(2)
      pulse (from 11.9 +/- 2 to 13.8 +/- 3 mL/bpm, P = 0.003). The Pilates group showed
      significantly increase in peak VO(2) when compared with conventional group (24.8
      +/- 6 vs. 18.3 +/- 4, P = 0.02). CONCLUSIONS: The result suggests that the
      Pilates method may be a beneficial adjunctive treatment that enhances functional
      capacity in patients with HF who are already receiving standard medical therapy.

PMID- 21884021
TI  - Atorvastatin inhibits homocysteine-induced endoplasmic reticulum stress through
      activation of AMP-activated protein kinase.
AB  - AIM: Accumulating evidence suggests that endoplasmic reticulum (ER) stress plays
      a fundamental role in the initiation and development of atherosclerosis.
      Atorvastatin is known to exert pleiotropic effects on cardiovascular system. This
      study was designed to examine the effect of atorvastatin on homocysteine (Hcy)
      induced activation of ER stress and the potential mechanisms regarding AMP
      activated protein kinase (AMPK). METHODS AND RESULTS: Apolipoprotein E-deficient
      (apoE(-/-)) mice were administrated with methionine or atorvastatin and
      sacrificed 2 months later for plasma tests and immunohistochemical analysis. To
      further study the mechanisms, human umbilical vein endothelial cells (HUVECs)
      were incubated with various concentrations of Hcy for 1 h, or 500 MUmol/L Hcy for
      1-24 h. Furthermore, we challenged HUVECs with Hcy in the presence or absence of
      atorvastatin, 5-amino-4-imidazolecarboxamide riboside-l-beta-D-ribofuranoside
      (AICAR), an AMPK agonist, and AMPK-DN that expressed a dominant-negative mutant
      of AMPK. Expression levels of ER stress markers were measured by real-time PCR
      and Western blot analysis. Our data revealed that atorvastatin prevented Hcy
      induced ER stress in the aortic roots of hyperhomocysteinemic mice. In vitro
      study showed atorvastatin suppressed Hcy-induced ER stress in HUVECs as well.
      AICAR is found to have the same effect as that of atorvastatin, which could be
      antagonized by AMPK-DN. CONCLUSIONS: Atorvastatin inhibits Hcy-induced ER stress
      both in vitro and in vivo. The protective effect of atorvastatin against Hcy
      induced vascular injury is mediated by AMPK activation.

PMID- 21884022
TI  - Estrogen receptor beta does not influence ischemic tolerance in the aged female
      rat heart.
AB  - INTRODUCTION: Ischemic heart disease remains the leading cause of morbidity and
      mortality in aged women, with a 2- to 3-fold increase in incidence following
      menopause. Clinical trials have failed to demonstrate cardioprotective benefit
      from chronic estrogen (E(2)) replacement therapy, yet protective effects of E(2)
      have been demonstrated in adult animal models and are mediated by the estrogen
      receptor (ER) subtypes ERalpha and ERbeta. AIMS: The aim of this study was to
      determine the effects of acute ERbeta activation on ischemia/reperfusion (I/R)
      injury in adult, aged, and aged E(2)-deficient female rats. METHODS: Hearts were
      isolated from adult (6 months; n = 9), aged (24 months; n = 13), and aged
      ovariectomized (OVX; n = 14) female Fischer 344 rats and subjected to 47 min of
      global I and 60 min of R. Rats were acutely treated with the ERbeta-agonist
      diarylpropionitrile (DPN; 5 MUg/kg) or vehicle 45 min prior to I/R; ERbeta mRNA
      and protein levels were also assessed. RESULTS: Acute treatment with DPN had no
      effect on functional recovery following I/R injury in adult, aged, or aged OVX
      female rats. Additionally, we were unable to detect ERbeta mRNA or protein in the
      adult or aged female rat myocardium. CONCLUSIONS: Here, for the first time, our
      data suggest that acute ERbeta activation does not impact ischemic tolerance in
      the adult or aged female Fischer 344 rat myocardium and this likely due to a lack
      of detectable ERbeta.

PMID- 21884023
TI  - A meta-analysis of impact of proton pump inhibitors on antiplatelet effect of
      clopidogrel.
AB  - Previous mechanistic studies have suggested a possible interaction between proton
      pump inhibitor (PPIs) and clopidogrel. However, the results of clinical trials
      about the effects of PPIs on safety and efficacy of clopidogrel are
      controversial. The study sought to estimate the impact of PPIs on antiplatelet
      effect of clopidogrel. The study performed a meta-analysis of comparative
      concomitant use of clopidogrel with PPIs versus clopidogrel without PPIs studies
      published or presented to October 2010. Cardiovascular death, readmission for
      myocardial infarction/readmission for acute coronary syndrome, and nonfatal
      stroke were set as clinical endpoints. In randomized control trials (RCTs), the
      clinical endpoints risk ratio for clopidogrel with PPIs versus clopidogrel
      without PPIs was 1.20 (P= 0.34) in the random-effects model and 1.03 (P= 0.63) in
      the fixed-effects model. In observational studies, the risk ratio for the
      clinical endpoints for clopidogrel with PPI versus clopidogrel without PPI was
      1.40 (P < 0.001) in the random-effects model and 1.49 (P < 0.001) in the fixed
      effects model. Different assay methods showed that coadministration of
      clopidogrel with PPIs was associated with attenuation of clopidogrel's
      antiplatelet effect in vitro. This meta-analysis indicated an obvious discrepancy
      between RCTs and observational studies with respect to the interaction between
      PPIs and clopidogrel.

PMID- 21884024
TI  - The role of OATP1B1 and BCRP in pharmacokinetics and DDI of novel statins.
AB  - The aim of this review is to provide useful information not only for studying the
      effect of OATP1B1 and/or BCRP gene mutation on pharmacokinetics of novle statins
      of pitavastatin and rosuvastatin but also for studying drug-drug interactions
      (DDI) between the novle statins and other substrates of OATP1B1 and/or BCRP.
      Intra- and inter-ethnic differences in pharmacokinetic profiles of clinically
      relevant drugs are important issues reported in many papers not only for scenes
      of appropriate drug used in clinical settings but also for those of the drug
      development. Pharmacogenomics is extremely useful for understanding these racial
      differences. Recent pharmacogenetics study have disclosed important roles of drug
      transporters in the pharmacokinetic (PK) profiles of some clinically relevant
      drugs. In this presentation, we introduce single nucleotide polymorphisms (SNPs)
      of OATP1B1 and BCRP and review the contribution of genetic polymorphisms of the
      transporters to the pharmacokinetics of dual substrates as pitavastatin and
      rosuvastatin from recent study. At the same time, the DDIs between pitavastatin
      or rosuvastatin and other drug have been extensively concerned because of
      inhibiting OATP1B1-mediated hepatic uptake or BCRP-mediated hepatic efflux of
      pitavastatin and rosuvastatin. This review summarized the current studies about
      the role of OATP1B1 and BCRP in DDIs between pitavastatin or rosuvastatin and
      other clinically relevant drugs. The role of OATP1B1 and BCRP gene mutation can
      affect the PK profiles of pitavastatin and rosuvastatin. The DDIs between the
      novle statins and other substrates of OATP1B1 or BCRP may occur and cause change
      in the pharmacokinetic of the novle statins.

PMID- 21884025
TI  - Is it cost-effective to increase aspirin use in outpatient settings for primary
      or secondary prevention? Simulation data from the REACH Registry Australian
      Cohort.
AB  - AIMS: To describe aspirin use in primary and secondary prevention and to
      determine the incremental costs-effectiveness ratio (ICER) per life year gain
      (LYG) of aspirin use among subjects with, or at high risk of atherothrombotic
      disease. DESIGN AND SUBJECTS: To project the cost-effectiveness of aspirin over 5
      years of follow-up, a Markov state transition model was developed with yearly
      cycles and the following health states: "Alive" (post-CAD) and "Dead." The model
      compared current coverage observed among 2361 subjects using the prospective
      Australian subset of Reduction of Atherothrombosis for continued Health (REACH)
      registry, and hypothetical situation whereby all subjects assumed to be treated.
      Costs were calculated based on the Australian government reimbursed data for
      2010. MAIN OUTCOME MEASURES: ICER per LYG for increased use of aspirin. RESULTS:
      The use of aspirin in current group varied from 67% to 70%. The base-case
      analysis showed that increasing aspirin use among subjects with existing CAD in
      outpatient settings was cost saving, while increasing use of aspirin in primary
      prevention equated to an ICER of AUD 7126 per LYG. CONCLUSION: Among subjects
      with existing CAD aspirin use was shown to be a dominant choice of treatment.
      However, among patients without existing cardiovascular disease (primary
      prevention), increased uptake of aspirin was cost effective but with uncertain
      benefit, with two hemorrhagic bleeding events occurring for every life saved.

PMID- 21884026
TI  - Combination angiotensin converting enzyme and direct renin inhibition in heart
      failure following experimental myocardial infarction.
AB  - AIMS: Diminishing the activity of the renin-angiotensin system (RAS) plays a
      pivotal role in the treatment of heart failure. In addition to angiotensin
      converting enzyme (ACE) inhibitors and angiotensin-receptor blockers, direct
      renin inhibition has emerged as a potential adjunctive treatment to conventional
      RAS blockade. We sought to determine the effectiveness of this strategy after
      myocardial infarction (MI) in the setting of preexisting hypertension, a common
      premorbid condition in patients with ischemic heart disease. METHODS AND RESULTS:
      Ten-week-old female heterozygous hypertensive (mRen-2)27 transgenic rats (Ren-2),
      were randomized to one of five groups (n = 8 per group); sham, MI, MI +
      aliskiren, MI + lisinopril and MI + combination lisinopril and aliskiren. Cardiac
      function was assessed by echocardiography and in vivo cardiac catheterization.
      Untreated MI animals developed heart failure with hypotension, dilation, reduced
      ejection fraction (EF), and raised left ventricular end-diastolic pressure
      (LVEDP). Treatment with single agent treatment had only modest effect on cardiac
      function though combination therapy was associated with significant improvements
      in EF and LVEDP when compared to untreated MI animals (P < 0.05). Histologic
      analysis demonstrated increase extracellular matrix deposition and cardiomyocyte
      hypertrophy in the noninfarct region of all MI groups when compared with sham
      operated animals (P < 0.05) that was reduced by ACE inhibitor monotherapy and
      combination treatment but not by aliskiren alone. CONCLUSION: In a hypertensive
      rat model that underwent experimental MI, EF, and LVEDP, key functional indices
      of heart failure, were improved by treatment with combination ACE and direct
      renin inhibition when compared with either agent used alone.

PMID- 21884027
TI  - Chronic pretreatment of metformin is associated with the reduction of the no
      reflow phenomenon in patients with diabetes mellitus after primary angioplasty
      for acute myocardial infarction.
AB  - INTRODUCTION: Metformin is one of the most commonly prescribed antihyperglycemic
      agents for the treatment of type 2 diabetes. However, little is known about the
      effect of metformin on no-reflow in diabetic patients. AIM: In this study, we
      investigated retrospectively whether chronic pretreatment with metformin was
      associated with no-reflow in diabetic patients who underwent primary coronary
      intervention for acute myocardial infarction (AMI). RESULTS: A total of 154
      consecutive diabetic patients who underwent primary angioplasty for a first ST
      segment elevation myocardial infarction were studied. No-reflow was defined as a
      final TIMI flow of <=2 or final TIMI flow of 3 with a myocardial blush grade of
      <2. The no-reflow phenomenon was found in 53 of 154 patients. There were no
      significant differences in clinical characteristics between the patients with and
      without metformin pretreatment. However, the 65 patients receiving chronic
      metformin treatment before admission had lower incidence of the no-reflow than
      those without it (4.2 and 14.6%, P < 0.05). Multivariable logistic regression
      analysis revealed that absence of metformin pretreatment was a significant
      predictor of the no-reflow along with high-burden thrombus, ejection fraction on
      admission and anterior AMI. CONCLUSION: These results suggested that chronic
      pretreatment with metformin may be associated with the reduction of the no-reflow
      phenomenon in patients with diabetes mellitus after primary angioplasty for AMI.

PMID- 21884029
TI  - Clopidogrel "resistance": where are we now?
AB  - Antiplatelet therapy with aspirin and clopidogrel in PCI patients, though
      effective, is still associated with thrombotic complications. These are
      multifactorial in origin, but partially attributable to "clopidogrel resistance."
      However, how best to identify and manage "clopidogrel resistance" remains
      unclear. Targeting therapeutic changes specifically at those individuals with
      poor response to clopidogrel is likely to be a solution. A "one size fits all"
      approach to clopidogrel dosing is probably flawed. This review will explore (1)
      the definition and mechanisms of clopidogrel resistance, (2) assessment of
      clopidogrel resistance by (i) platelet function testing and (ii) genetic testing,
      (3) the management of "clopidogrel resistance," and (4) newer antiplatelet
      agents, and evolving stent technology. A pubmed literature review was performed
      using the keywords "clopidogrel", "resistance", "poor response", "adverse
      events", "platelet function tests", and "genetic tests". In looking at new
      agents, keywords "prasugrel", "cangrelor", "ticagrelor""Elinogrel", and "P2Y12
      receptor antagonists" were used. Third, a search was performed looking at "stent
      design", "IVUS", "bioabsorbable stents", and "stent apposition". Whilst new P2Y12
      receptor antagonists and improved stent technology may reduce thrombotic events
      in the future, there is still a need for clopidogrel. There is good evidence that
      poor response to clopidogrel is associated with adverse outcome. Platelet
      function tests probably provide more clinically useful data than genetic tests,
      but the question of how best to identify and manage variability in response to
      clopidogrel demands further research.

PMID- 21884028
TI  - A dosing algorithm for erythropoietin alpha in older adults with heart failure
      and a preserved ejection fraction.
AB  - AIMS: Erythropoietin stimulating agents (ESAs) is an active area of clinical
      investigation in heart failure (HF) but can cause hypertension and higher
      hemoglobin concentrations (Hb) that have been associated with adverse outcomes.
      We evaluated a dosing algorithm and potential confounders' effect on Hb and blood
      pressure (BP) in a clinical trial. METHODS: In an ongoing randomized, placebo
      controlled, single blind clinical trial of ESA (epoetin alfa) in anemic patients
      with HF and a preserved ejection fraction (HFPEF), Hb was measured weekly as was
      BP, weight and concomitant medical therapy. A repeated measure mixed model
      evaluated determinants of weekly changes in Hb and BP. RESULTS: Among 45 subjects
      (78 +/- 11 years, 67% women, EF = 57 +/- 9%) with a total of 780 repeated weekly
      Hb measures, Hb significantly increased over time in those assigned to ESA (beta
      = 0.933, P < 0.0001), compared to placebo. Dose (beta = -0.108, P < 0.0001),
      patient weight (beta = -0.016, P = 0.0037), diuretic use (beta = -0.124, P =
      0.0389), and time (beta = 0.003, P = 0.0331), were all significantly associated
      with Hb change. Increased diuretic dose and weight change were significantly
      inversely associated with changes in Hb. ESA administration and dose were not
      significant determinants of absolute BP or changes in BP from baseline.
      DISCUSSION: In addition to ESA dose and duration of therapy, factors indicative
      of volume status including weight and diuretic use are determinants of hemoglobin
      levels in HF subjects. CONCLUSION: The currently employed dosing algorithm, which
      adjusts the administration of ESA based on the absolute hemoglobin and weekly
      change in hemoglobin increases Hb with relatively a low weekly dose of ESA
      without significant effects on BP.

PMID- 21884031
TI  - Is angiotensin-converting enzyme inhibitor a contraindication for contrast
      induced nephropathy prophylaxis? A review about its paradox.
AB  - Contrast-induced nephropathy (CIN) is reported to be the third leading cause of
      acute renal failure. The role of angiotensin-converting enzyme (ACE) inhibitors
      in CIN is controversial. Some studies pointed out that it was effective in the
      prevention of CIN, while some concluded that it was associated with increased
      risk of CIN, especially for patients with preexisting renal impairment.
      Nevertheless, it is a common practice in many centers to prescribe ACE inhibitors
      before coronary angiography. The most likely mechanisms leading to CIN are
      medullary hypoxia due to decreased renal blood flow (RBF) secondary to renal
      artery vasoconstriction and direct tubular toxicity by contrast medium (CM).
      Furthermore, experimental data suggest that an activated renin-angiotensin
      aldosterone system, increased endothelin-1, and reactive oxygen species play a
      role in the pathogenesis of CIN and these can be inhibited by using ACE
      inhibitors. In this context, we review the medical literatures and discuss the
      pathogenesis, the role of renin-angiotensin-aldosterone system on the development
      of CIN and ACE inhibitors' effect on CIN.

PMID- 21884030
TI  - Effects of the recombinant form of the natural human B-type natriuretic peptide
      and levosimendan on pulmonary hyperventilation and chemosensivity in heart
      failure.
AB  - BACKGROUND: The origin of dyspnea in chronic heart failure (HF) is
      multifactorial, and excessive ventilation is thought to play a role in inducing
      this symptom. Chemosensivity is augmented in HF, correlates with increased
      pulmonary ventilation (VE), and is an adverse prognostic marker. Despite
      increased blood levels of natriuretic peptides in clinical conditions associated
      with dyspnea, their effect on pulmonary VE and chemoreceptor activity remains
      unexplored. METHODS: We tested in a prospective, placebo-controlled, three-way
      cross-over, double-blind randomized study the effects of the recombinant form of
      the natural human B-type natriuretic peptide (R-BNP) in comparison with placebo
      and levosimendan on chemoreflex sensitivity at rest, as well as their effects on
      pulmonary VE, systemic blood pressure, heart rate and sympathetic serum activity
      both at rest and during exercise. RESULTS: Eleven stable chronic HF patients were
      randomized to sessions of 6-min treadmill-walking tests during placebo, or
      levosimendan or R-BNP intravenous infusion in the following conditions: room air,
      hypoxia, and hypercapnia. R-BNP administration determined higher pulmonary
      ventilatory response at rest and during exercise (P < 0.001) consequent to a
      boost of respiratory rate (P < 0.001) under room air and hypoxia conditions.
      Norepinephrine blood levels increased from rest to exercise in all conditions
      without differences among placebo, levosimendan, and R-BNP effects. BNP blood
      levels remained unchanged. CONCLUSIONS: The novelty of the present findings is
      that R-BNP infusion in HF patients can boost pulmonary ventilatory response at
      rest and during exercise.

PMID- 21884033
TI  - A survey of the risk of zoonoses for veterinarians.
AB  - The objectives of this study were to identify factors associated with zoonotic
      infections in veterinarians, the incidence of physician consultation and
      treatment and the incidence of diagnostic and treatment errors. Veterinarians in
      any area of practice were solicited to participate in an online survey through an
      invitation letter sent to the Oregon Veterinary Medical Association. Proportions
      of respondents to various factors were analyzed for differences among gender,
      age, time since graduation and type of practice in which they worked. In all, 216
      complete responses were received. In all, 13.9% of respondents had never been
      vaccinated against rabies, and 20.8% had been exposed to suspect rabid animals,
      mostly (64.4%) a single time. Other zoonoses were reported by 47.2% of
      respondents: mostly diseases transmitted via contact (57.4%) especially ringworm,
      followed by those with oral transmission (21.7%). Most zoonotic infections were
      reportedly acquired by young veterinarians working in primary care veterinary
      practice. Cats were the species most commonly reported as the animal source of a
      zoonotic infection. Veterinarians likely self-diagnosed zoonotic diseases,
      especially those transmitted by contact. Medical care providers were consulted
      for diagnosis of more serious diseases. Diagnosis and treatment errors were
      uncommon. Results of this study emphasize the need to educate future
      veterinarians during their early years in veterinary school about the risks
      associated with their future jobs.

PMID- 21884032
TI  - Seroprevalence and risk factors associated with Escherichia coli O157 in a
      farming population.
AB  - Evidence suggests that frequent and direct exposure to domestic animals has made
      farmers less susceptible to symptomatic Escherichia coli O157 infection than
      other members of the community. We have quantified the seroprevalence of
      antibodies to E. coli O157 lipopolysaccharide (LPS) from a representative cohort
      of farm workers in three geographically distinct regions of the United Kingdom
      during two sampling rounds over a 2-year period. All participants completed a
      questionnaire to determine the range and extent of recent animal contact
      alongside other potential occupational and environmental exposure routes. A total
      of 31/946 (3.3%) serum samples contained antibodies to E. coli O157 LPS (from
      both rounds combined). On the second sampling round, a significant difference in
      seropositivity was apparent between the three regions, with enhanced
      seroprevalence linked to recent contact with beef cattle, having a private water
      supply and contact with a child under 5 years old. Only five seropositive people
      reported symptoms of a gastrointestinal tract infection, although these symptoms
      were mild. These results further support the premise of acquired immunity to E.
      coli O157 associated with prolonged antigenic exposures within the farming
      environment.

PMID- 21884034
TI  - Development of an algorithm for assessing the risk to food safety posed by a new
      animal disease.
AB  - An algorithm was developed as a tool to rapidly assess the potential for a new or
      emerging disease of livestock to adversely affect humans via consumption or
      handling of meat product, so that the risks and uncertainties can be understood
      and appropriate risk management and communication implemented. An algorithm
      describing the sequence of events from occurrence of the disease in livestock,
      release of the causative agent from an infected animal, contamination of fresh
      meat and then possible adverse effects in humans following meat handling and
      consumption was created. A list of questions complements the algorithm to help
      the assessors address the issues of concern at each step of the decision pathway.
      The algorithm was refined and validated through consultation with a panel of
      experts and a review group of animal health and food safety policy advisors via
      five case studies of potential emerging diseases of cattle. Tasks for model
      validation included describing the path taken in the algorithm and stating an
      outcome. Twenty-nine per cent of the 62 experts commented on the model, and one
      third of those responding also completed the tasks required for model validation.
      The feedback from the panel of experts and the review group was used to further
      develop the tool and remove redundancies and ambiguities. There was agreement in
      the pathways and assessments for diseases in which the causative agent was well
      understood (for example, bovine pneumonia due to Mycoplasma bovis). The stated
      pathways and assessments of other diseases (for example, bovine Johne's disease)
      were not as consistent. The framework helps to promote objectivity by requiring
      questions to be answered sequentially and providing the opportunity to record
      consensus or differences of opinion. Areas for discussion and future
      investigation are highlighted by the points of diversion on the pathway taken by
      different assessors.

PMID- 21884037
TI  - Porphyria cutanea tarda, iron, inflammation and diabetes mellitus.

PMID- 21884035
TI  - Outcome of three commercial serum ELISAs and faecal detection of Mycobacterium
      avium subsp. paratuberculosis in consecutive samples from a cattle herd with low
      prevalence of paratuberculosis (Johne's disease).
AB  - Paratuberculosis (Johne's disease) in ruminants is caused by Mycobacterium avium
      subsp. paratuberculosis (MAP). Owing to the lack of accurate laboratory tests,
      diagnosis is challenging in subclinically infected cattle. To evaluate the long
      term performance of serum ELISAs for the detection of paratuberculosis in a dairy
      herd with low MAP-prevalence, three investigations of all the cows and the
      consecutive testing of 33 cows suspected to be infected with MAP and 30 cows
      classified as MAP free were performed over a period of 22 months. Blood samples
      were tested by three commercial serum ELISAs, MAP shedding was detected by
      bacteriological culture and polymerase chain reaction (PCR). The ELISA results
      varied in a wide range in the herd investigations with 1.2% to 18.8% positive
      samples, the faecal samples were positive for MAP between 1.8% and 4.9% in the
      three herd investigations. Over the study period, ELISA-positive serum samples
      varied between 0.0% and 69.7% in MAP-suspicious and 0.0% and 17.6% in MAP
      unsuspicious cows with a poor correlation between ELISAs and faecal shedding. The
      correlation coefficient of the optical density values of the three ELISAs varied
      between 0.348 and 0.61. Evidence of cow specific variations of residuals was
      found in all linear models. The linear mixed models showed relevant contribution
      of cow specific variation in explanation of the residual variances. They also
      showed significant effects of the explanatory ELISA, the group (MAP-suspicious or
      MAP-unsuspicious) and the time of sampling. It can be concluded that the choice
      of the laboratory test significantly influences the outcome of the testing for
      MAP and that none of the three ELISAs can be thoroughly recommended as single
      test for the early diagnosis of paratuberculosis in cattle. Test results should
      always be interpreted with caution to avoid erroneous decisions and the
      disappointment of those engaged in the abatement of paratuberculosis.

PMID- 21884038
TI  - A biased comment on double-blind review.

PMID- 21884039
TI  - Comparison of psoralen plus ultraviolet A therapy and biologics in moderate to
      severe chronic plaque psoriasis.

PMID- 21884040
TI  - Life-style factors and hand eczema.

PMID- 21884041
TI  - Eczema and cancer risk: a critical appraisal and review of the literature.
AB  - AIM: Hwang et al. aimed to evaluate the risk of malignancy among individuals with
      eczema, allergic rhinitis (AR) and asthma, compared with the general Taiwanese
      population. HYPOTHESIS: People with atopic conditions, including eczema, have an
      altered risk of malignancy. SETTING AND DESIGN: This was a prospective nationwide
      cohort study. The authors used the Taiwanese National Health Insurance Research
      Database (NHIRD) to compare the incidence of cancers among people with
      established allergic disease relative to the risk in the general population.
      STUDY EXPOSURE: Exposure was the presence of one or more atopic conditions
      (eczema, AR or asthma). Data were extracted on 997,729 randomly selected people
      registered on the NHIRD at any time point between 1996 and 2008. Eczema was
      identified via ICD-9-CM codes with the diagnosis being made by a dermatologist,
      paediatrician or allergist. Follow-up was until 2008, date of first cancer or
      death. OUTCOMES: The outcome was a new diagnosis of malignancy, identified via
      catastrophic illness insurance certificates, again using ICD-9-CM diagnostic
      codes. PRIMARY OUTCOME MEASURE: Standardized incidence ratios (SIRs) for cancers
      overall and different types of malignancy among patients with eczema, AR or
      asthma were calculated against the expected number of cancer cases in the general
      population, adjusted for age and sex. RESULTS: The number of patients identified
      with eczema, AR and asthma was 34,263, 225,315 and 107,601, respectively. Overall
      cancer rates in patients with these conditions were not significantly different
      from those in the general population [SIR eczema = 0.97 (95% confidence interval
      0.87-1.09), SIR AR = 1.02 (0.98-1.05) and SIR asthma = 1.01 (0.97-1.04)].
      However, when the results for eczema were stratified by age, people aged between
      20 and 39 years appeared to have a 56% increase in risk in relation to 'any
      cancer' [SIR = 1.56 (1.13-2.09)]. Looking at individual cancer types in patients
      with eczema, only the risk of brain cancer was significantly raised [SIR = 2.52
      (1.15-4.79)]. Patients who had had all three allergic conditions had a reduced
      SIR for 'cancers overall' [SIR = 0.59 (0.37-0.88)]. This inverse association was
      less strong for those with eczema and asthma [SIR = 0.73 (0.55-0.97)] or asthma
      and AR [SIR = 0.79 (0.73-0.84)] and statistically only of borderline significance
      for those with eczema and AR [SIR = 0.85 (0.67-1.07)]. CONCLUSIONS: Hwang et al.
      conclude that the relationship between allergic diseases and cancer risk is
      complex and site specific. The risk of malignancy was highest in all atopic
      conditions in the 20-39-year age group. In patients with eczema, the incidence of
      brain cancer was higher than expected, which the authors note is at odds with
      previous studies. However, numbers were too small to allow stratification by
      histological subtypes. The authors warn against deriving conclusions for rarer
      cancers and that borderline SIRs must be interpreted with caution.

PMID- 21884042
TI  - Response to eczema and cancer risk: a critical appraisal and review of the
      literature.

PMID- 21884043
TI  - Commentary: eczema and cancer risk.

PMID- 21884044
TI  - How can we tell if frogs jump further?

PMID- 21884046
TI  - Recombination and hitchhiking of deleterious alleles.
AB  - When new advantageous alleles arise and spread within a population, deleterious
      alleles at neighboring loci can hitchhike alongside them and spread to fixation
      in areas of low recombination, introducing a fixed mutation load. We use
      branching processes and diffusion equations to calculate the probability that a
      deleterious allele hitchhikes and fixes alongside an advantageous mutant. As
      expected, the probability of fixation of a deleterious hitchhiker rises with the
      selective advantage of the sweeping allele and declines with the selective
      disadvantage of the deleterious hitchhiker. We then use computer simulations of a
      genome with an infinite number of loci to investigate the increase in load after
      an advantageous mutant is introduced. We show that the appearance of advantageous
      alleles on genetic backgrounds loaded with deleterious alleles has two potential
      effects: it can fix deleterious alleles, and it can facilitate the persistence of
      recombinant lineages that happen to occur. The latter is expected to reduce the
      signals of selection in the surrounding region. We consider these results in
      light of human genetic data to infer how likely it is that such deleterious
      hitchhikers have occurred in our recent evolutionary past.

PMID- 21884048
TI  - Sperm competition and mate harm unresponsive to male-limited selection in
      Drosophila: an evolving genetic architecture under domestication.
AB  - Earlier research by W.R. Rice showed that experimentally limiting gene expression
      to males in Drosophila melanogaster leads to the rapid evolution of higher
      fitness. Using a similar male-limited (ML) selection protocol, we confirmed that
      result and showed that eliminating intralocus sexual conflict results in a
      comprehensive remodeling of the sexually dimorphic phenotype. However, despite
      starting from laboratory-evolved descendants of the same founder population used
      in earlier work, we found no evidence for the increased performance in sperm
      competition or increased postmating harm to females previously demonstrated. We
      employed females with both ancestral population genotypes and those of the
      special "clone generator" females used in ML selection. Despite strong
      differences in sperm storage or usage patterns between these females, there was
      no detectable adaptation by males to the specific female stock used in the
      selection protocol. The lack of evolution of postcopulatory traits suggests
      either that requisite genetic variation was eliminated by long-term domestication
      of the base population, or that complex male-by-male-by-female interactions made
      these traits unavailable to selection. The different evolutionary outcomes
      produced by two very similar experiments done at different time points
      underscores the potential for cryptic adaptation in the laboratory to
      qualitatively affect inferences made using quantitative genetic methodologies.

PMID- 21884047
TI  - Polyandry and the decrease of a selfish genetic element in a wild house mouse
      population.
AB  - Despite deleterious effects on individuals, the t haplotype is a selfish genetic
      element present in many house mouse populations. By distorting the transmission
      ratio, +/t males transmit the t haplotype to up to 90% of their offspring.
      However, t/t individuals perish in utero. Theoretical models based on these
      properties predict a much higher t frequency than observed, leading to the t
      paradox. Here, we use empirical field data and theoretical approaches to
      investigate whether polyandry is a female counterstrategy against the negative
      fitness consequences of such distorters. We found a significant decrease of the t
      frequency over a period of 5.5 years that cannot be explained by the effect of
      transmission ratio distortion and recessive lethals, despite significantly higher
      life expectancy of +/t females compared to +/+ females. We quantified life
      history data and homozygous and heterozygous fitness effects. Population
      subdivision and inbreeding were excluded as evolutionary forces influencing the t
      system. The possible influence of polyandry on the t system was then investigated
      by applying a stochastic model to this situation. Simulations show that polyandry
      can explain the observed t dynamics, making it a biologically plausible
      explanation for low t frequencies in natural populations in general.

PMID- 21884049
TI  - Assortative mating counteracts the evolution of dispersal polymorphisms.
AB  - Polymorphic dispersal strategies are found in many plant and animal species. An
      important question is how the genetic variation underlying such polymorphisms is
      maintained. Numerous mechanisms have been discussed, including kin competition or
      frequency-dependent selection. In the context of sympatric speciation events,
      genetic and phenotypic variation is often assumed to be preserved by assortative
      mating. Thus, recently, this has been advocated as a possible mechanism leading
      to the evolution of dispersal polymorphisms. Here, we examine the role of
      assortative mating for the evolution of trade-off-driven dispersal polymorphisms
      by modeling univoltine insect species in a metapopulation. We show that
      assortative mating does not favor the evolution of polymorphisms. On the
      contrary, assortative mating favors the evolution of an intermediate dispersal
      type and a uni-modal distribution of traits within populations. As an
      alternative, mechanism dominance may explain the occurrence of two discrete
      morphs.

PMID- 21884050
TI  - Genetic admixture in multidimensional environmental space: asymmetrical niche
      similarity promotes gene flow in armadillos (Dasypus novemcinctus).
AB  - We unite genetic data with a robust test of niche divergence to test the
      hypothesis that patterns of gene flow between two lineages of the nine-banded
      armadillo are influenced by their climatic niches. We collected Geographical
      Information System (GIS) data on climate using locality information from 111
      individuals from two lineages that had associated genetic material. We tested
      whether niches of these lineages were more conserved or divergent than the
      background environments of their geographic ranges and found evidence for niche
      conservatism on two axes and no evidence for divergence on any axis. To address
      the role of niche similarity in gene flow, we genotyped the 111 individuals at
      five microsatellite loci and tested whether admixed individuals tended to be
      located in parts of multidimensional environmental space (E-space) shared between
      the two lineages. We observed an asymmetrical pattern of overlap, in which the
      West lineage's E-space was almost completely included inside East lineage's E
      space. Genetic admixture levels were significantly higher in the West lineage
      and, for both lineages, in shared portions of E-space. This suggests that niche
      similarity can facilitate gene flow among disjunct groups with moderate-to-good
      dispersal capabilities, contrasting with the prevailing view of niche
      conservatism as a diversifying force.

PMID- 21884051
TI  - Effects of founding genetic variation on adaptation to a novel resource.
AB  - Population genetic theory predicts that adaptation in novel environments is
      enhanced by genetic variation for fitness. However, theory also predicts that
      under strong selection, demographic stochasticity can drive populations to
      extinction before they can adapt. We exposed wheat-adapted populations of the
      flour beetle (Tribolium castaneum) to a novel suboptimal corn resource, to test
      the effects of founding genetic variation on population decline and subsequent
      extinction or adaptation. As previously reported, genetically diverse populations
      were less likely to go extinct. Here, we show that among surviving populations,
      genetically diverse groups recovered faster after the initial population decline.
      Within two years, surviving populations significantly increased their fitness on
      corn via increased fecundity, increased egg survival, faster larval development,
      and higher rate of egg cannibalism. However, founding genetic variation only
      enhanced the increase in fecundity, despite existing genetic variation-and
      apparent lack of trade-offs-for egg survival and larval development time. Thus,
      during adaptation to novel habitats the positive impact of genetic variation may
      be restricted to only a few traits, although change in many life-history traits
      may be necessary to avoid extinction. Despite severe initial maladaptation and
      low population size, genetic diversity can thus overcome the predicted high
      extinction risk in new habitats.

PMID- 21884052
TI  - Comparing environmental and genetic variance as adaptive response to fluctuating
      selection.
AB  - Phenotypic variation within populations has two sources: genetic variation and
      environmental variation. Here, we investigate the coevolution of these two
      components under fluctuating selection. Our analysis is based on the lottery
      model in which genetic polymorphism can be maintained by negative frequency
      dependent selection, whereas environmental variation can be favored due to bet
      hedging. In our model, phenotypes are characterized by a quantitative trait under
      stabilizing selection with the optimal phenotype fluctuating in time. Genotypes
      are characterized by their phenotypic offspring distribution, which is assumed to
      be Gaussian with heritable variation for its mean and variance. Polymorphism in
      the mean corresponds to genetic variance while the width of the offspring
      distribution corresponds to environmental variance. We show that increased
      environmental variance is favored whenever fluctuations in the selective optima
      are sufficiently strong. Given the environmental variance has evolved to its
      optimum, genetic polymorphism can still emerge if the distribution of selective
      optima is sufficiently asymmetric or leptokurtic. Polymorphism evolves in a
      diagonal direction in trait space: one type becomes a canalized specialist for
      the more common ecological conditions and the other type a de-canalized bet
      hedger thriving on the less-common conditions. All results are based on
      analytical approximations, complemented by individual-based simulations.

PMID- 21884053
TI  - Population divergence along lines of genetic variance and covariance in the
      invasive plant Lythrum salicaria in eastern North America.
AB  - Evolution during biological invasion may occur over contemporary timescales, but
      the rate of evolutionary change may be inhibited by a lack of standing genetic
      variation for ecologically relevant traits and by fitness trade-offs among them.
      The extent to which these genetic constraints limit the evolution of local
      adaptation during biological invasion has rarely been examined. To investigate
      genetic constraints on life-history traits, we measured standing genetic variance
      and covariance in 20 populations of the invasive plant purple loosestrife
      (Lythrum salicaria) sampled along a latitudinal climatic gradient in eastern
      North America and grown under uniform conditions in a glasshouse. Genetic
      variances within and among populations were significant for all traits; however,
      strong intercorrelations among measurements of seedling growth rate, time to
      reproductive maturity and adult size suggested that fitness trade-offs have
      constrained population divergence. Evidence to support this hypothesis was
      obtained from the genetic variance-covariance matrix (G) and the matrix of
      (co)variance among population means (D), which were 79.8% (95% C.I. 77.7-82.9%)
      similar. These results suggest that population divergence during invasive spread
      of L. salicaria in eastern North America has been constrained by strong genetic
      correlations among life-history traits, despite large amounts of standing genetic
      variation for individual traits.

PMID- 21884054
TI  - Rapid evolution of fire melanism in replicated populations of pygmy grasshoppers.
AB  - Evolutionary theory predicts an interactive process whereby spatiotemporal
      environmental heterogeneity will maintain genetic variation, while genetic and
      phenotypic diversity will buffer populations against stress and allow for fast
      adaptive evolution in rapidly changing environments. Here, we study color
      polymorphism patterns in pygmy grasshoppers (Tetrix subulata) and show that the
      frequency of the melanistic (black) color variant was higher in areas that had
      been ravaged by fires the previous year than in nonburned habitats, that, in
      burned areas, the frequency of melanistic grasshoppers dropped from ca. 50% one
      year after a fire to 30% after four years, and that the variation in frequencies
      of melanistic individuals among and within populations was genetically based on
      and represented evolutionary modifications. Dark coloration may confer a
      selective benefit mediated by enhanced camouflage in recently fire-ravaged areas
      characterized by blackened visual backgrounds before vegetation has recovered.
      These findings provide rare evidence for unusually large, extremely rapid
      adaptive contemporary evolution in replicated natural populations in response to
      divergent and fluctuating selection associated with spatiotemporal environmental
      changes.

PMID- 21884055
TI  - Rapid evolution caused by pollinator loss in Mimulus guttatus.
AB  - Anthropogenic perturbations including habitat loss and emerging disease are
      changing pollinator communities and generating novel selection pressures on plant
      populations. Disruption of plant-pollinator relationships is predicted to cause
      plant mating system evolution, although this process has not been directly
      observed. This study demonstrates the immediate evolutionary effects of
      pollinator loss within experimental populations of a predominately outcrossing
      wildflower. Initially equivalent populations evolved for five generations within
      two pollination treatments: abundant bumblebee pollinators versus no pollinators.
      The populations without pollinators suffered greatly reduced fitness in early
      generations but rebounded as they evolved an improved ability to self-fertilize.
      All populations diverged in floral, developmental, and life-history traits, but
      only a subset of characters showed clear association with pollination treatment.
      Pronounced treatment effects were noted for anther-stigma separation and
      autogamous seed set. Dramatic allele frequency changes at two chromosomal
      polymorphisms occurred in the no pollinator populations, explaining a large
      fraction of divergence in pollen viability. The pattern of phenotypic and genetic
      changes in this experiment favors a sequential model for the evolution of the
      multitrait "selfing syndrome" observed throughout angiosperms.

PMID- 21884056
TI  - Sexual dimorphism and speciation on two ecological coins: patterns from nature
      and theoretical predictions.
AB  - Adaptive divergence of phenotypes, such as sexual dimorphism or adaptive
      speciation, can result from disruptive selection via competition for limited
      resources. Theory indicates that speciation and sexual dimorphism can result from
      identical ecological conditions, but co-occurrence is unlikely because whichever
      evolves first should dissipate the disruptive selection necessary to drive
      evolution of the other. Here, we consider ecological conditions in which
      disruptive selection can act along multiple ecological axes. Speciation in lake
      populations of threespine sticklebacks (Gasterosteus aculeatus) has been
      attributed to disruptive selection due to competition for resources. Head shape
      in sticklebacks is thought to reflect adaptation to different resource
      acquisition strategies. We measure sexual dimorphism and species variation in
      head shape and body size in stickleback populations in two lakes in British
      Columbia, Canada. We find that sexual dimorphism in head shape is greater than
      interspecific differences. Using a numerical simulation model that contains two
      axes of ecological variation, we show that speciation and sexual dimorphism can
      readily co-occur when the effects of loci underlying sexually dimorphic traits
      are orthogonal to those underlying sexually selected traits.

PMID- 21884057
TI  - Contrasting theory with the empirical data of species recognition.
AB  - We tested hypotheses on how animals should respond to heterospecifics encountered
      in the environment. Hypotheses were formulated from models parameterized to
      emphasize four factors that are expected to influence species discrimination:
      mating and territorial interactions; sex differences in resource value;
      environments in which heterospecifics were common or rare; and the type of
      identity cues available for species recognition. We also considered the role of
      phylogeny on contemporary responses to heterospecifics. We tested the extent
      these factors explained variation among taxa in species discrimination using a
      meta-analysis of three decades of species recognition research. A surprising
      outcome was the absence of a general predictor of when species discrimination
      would most likely occur. Instead, species discrimination is dictated by the
      benefits and costs of responding to a conspecific or heterospecific that are
      governed by the specific circumstances of a given species. The phylogeny of
      species recognition provided another unexpected finding: the evolutionary
      relationships among species predicted whether courting males within species-but
      not females-would discriminate against heterospecifcs. This implies that species
      recognition has evolved quite differently in the sexes. Finally, we identify
      common pitfalls in experimental design that seem to have affected some studies
      (e.g., poor statistical power) and provide recommendations for future research.

PMID- 21884058
TI  - Hybridization, species collapse, and species reemergence after disturbance to
      premating mechanisms of reproductive isolation.
AB  - There are now a number of well-studied cases in which hybridization between
      closely related sympatric species has increased, sometimes resulting in the
      replacement of species pairs by hybrid swarms. Many of these cases have been
      linked to anthropogenic environmental change, but the mechanisms leading from
      environmental change to species collapse, and the long-term effects of
      hybridization on species pairs, remain poorly understood. We used an individual
      based stochastic simulation model to explore the conditions under which
      disturbances that weaken premating barriers to reproduction patterns between
      sympatric species might lead to increased hybridization and to species collapse.
      Disturbances often resulted in bouts of hybridization, but in many cases strong
      reproductive isolation spontaneously reemerged. This was sometimes true even
      after hybrid swarms had replaced parental species. The reemergence of species
      pairs was most likely when disturbances were of short duration.
      Counterintuitively, incipient species pairs were more likely to reemerge after
      strong but temporary disturbances than after weaker disturbances of the same
      duration. Even temporary bouts of hybridization often led to substantial
      homogenization of species pairs. This suggests that ecosystem managers may be
      able to refill ecological niches, but in general will not be able to resurrect
      lost species after species collapse.

PMID- 21884059
TI  - Floral isolation is the main reproductive barrier among closely related sexually
      deceptive orchids.
AB  - Floral isolation is an important component of pollinator-driven speciation.
      However, up to now, only a few studies have quantified its strength and relative
      contribution to total reproductive isolation. In this study, we quantified floral
      isolation among three closely related, sympatric orchid species of the genus
      Ophrys by directly tracking pollen flow. Ophrys orchids mimic their pollinators'
      mating signals, and are pollinated by male insects during mating attempts. This
      pollination system, called sexual deception, is usually highly specific. However,
      whether pollinator specialization also conveys floral isolation is currently
      under debate. In this study, we found strong floral isolation: among 46 tracked
      pollen transfers in two flowering seasons, all occurred within species.
      Accounting for observation error rate, we estimated a floral isolation index
      >=0.98 among each pair of species. Hand pollination experiments suggested that
      postpollination barriers were effectively absent among our study species. Genetic
      analysis based on AFLP markers showed a clear species clustering and very few
      F(1) hybrids in natural populations, providing independent evidence that strong
      floral isolation prevents significant interspecies gene flow. Our results provide
      the first direct evidence that floral isolation acts as the main reproductive
      barrier among closely related plant species with specialized pollination.

PMID- 21884061
TI  - The role of different reproductive barriers during phenotypic divergence of
      isopod ecotypes.
AB  - The question of how diverging populations become separate species by restraining
      gene flow is a central issue in evolutionary biology. Assortative mating might
      emerge early during adaptive divergence, but the role of other types of
      reproductive barriers such as migration modification have recently received
      increased attention. We demonstrate that two recently diverged ecotypes of a
      freshwater isopod (Asellus aquaticus) have rapidly developed premating isolation,
      and this isolation barrier has emerged independently and in parallel in two south
      Swedish lakes. This is consistent with ecological speciation theory, which
      predicts that reproductive isolation arises as a byproduct of ecological
      divergence. We also find that in one of these lakes, habitat choice acts as the
      main barrier to gene flow. These observations and experimental results suggest
      that migration modification might be as important as assortative mating in the
      early stages of ecological speciation. Simulations suggest that the joint action
      of these two isolating barriers is likely to greatly facilitate adaptive
      divergence, compared to if each barrier was acting alone.

PMID- 21884060
TI  - Heterozygosity and its unexpected correlations with hybrid sterility.
AB  - In general, heterozygosity is considered to be advantageous, primarily because it
      masks the effects of deleterious recessive alleles. However, there is usually a
      reduction in fitness in individuals that are heterozygous due to the pairing of
      two species (heterospecific). Because the parental alleles arose along separate
      evolutionary paths, they may not function properly when brought together within
      an individual. The formation of these unfit interspecies hybrids is one of the
      mechanisms that maintains species isolation. Interestingly, it has been observed
      that later-generation individuals resulting from a backcross to one parent are
      more often sterile than those resulting from a backcross to the other parent, but
      the mechanism underlying this trend is unknown. Here, I show that one direction
      of backcross produces offspring with more heterospecific genome, and that this is
      correlated with the directionality seen in backcross hybrid sterility. Therefore,
      the directionality in sterility is likely due to the different amounts of
      heterospecific genome present in the two backcrosses. Surprisingly, in spite of
      the potential fitness consequences, I also find that interspecies laboratory
      backcrosses in general yield an excess of heterospecific individuals, and that
      this trend is consistent across multiple taxa.

PMID- 21884062
TI  - Evidence for repeated acquisition and loss of complex body-form characters in an
      insular clade of Southeast Asian semi-fossorial skinks.
AB  - Evolutionary simplification, or loss of complex characters, is a major theme in
      studies of body-form evolution. The apparently infrequent evolutionary
      reacquisition of complex characters has led to the assertion (Dollo's Law) that
      once lost, complex characters may be impossible to re-evolve, at least via the
      exact same evolutionary process. Here, we provide one of the most comprehensive,
      fine-scale analyses of squamate body-form evolution to date, introducing a new
      model system of closely related, morphologically variable, lizards. Our
      phylogenetic results support independent instances of complete limb loss as well
      as multiple instances of digit and external ear opening loss and re-acquisition.
      Even more striking, we find strong statistical support for the re-acquisition of
      a pentadactyl body form from a digit-reduced ancestor. Our study reveals that
      species of the genus Brachymeles exemplify regions of morphospace (body plans)
      previously undocumented in squamates. Our findings have broad, general
      implications for body-form evolution in burrowing vertebrates: whatever
      constraints have shaped trends in morphological evolution among other squamate
      groups (excluding Bipes) have been lost in this one exemplary clade. The results
      of our study join a nascent body of literature showing strong statistical support
      for character loss, followed by evolutionary re-acquisition of complex structures
      associated with a generalized pentadactyl body form.

PMID- 21884063
TI  - Evolution of extreme body size disparity in monitor lizards (Varanus).
AB  - Many features of species' biology, including life history, physiology,
      morphology, and ecology are tightly linked to body size. Investigation into the
      causes of size divergence is therefore critical to understanding the factors
      shaping phenotypic diversity within clades. In this study, we examined size
      evolution in monitor lizards (Varanus), a clade that includes the largest extant
      lizard species, the Komodo dragon (V. komodoensis), as well as diminutive species
      that are nearly four orders of magnitude smaller in adult body mass. We
      demonstrate that the remarkable body size disparity of this clade is a
      consequence of different selective demands imposed by three major habitat use
      patterns-arboreality, terrestriality, and rock-dwelling. We reconstructed
      phylogenetic relationships and ancestral habitat use and applied model selection
      to determine that the best-fitting evolutionary models for species' adult size
      are those that infer oppositely directed adaptive evolution associated with
      terrestriality and rock-dwelling, with terrestrial lineages evolving extremely
      large size and rock-dwellers becoming very small. We also show that habitat use
      affects the evolution of several ecologically important morphological traits
      independently of body size divergence. These results suggest that habitat use
      exerts a strong, multidimensional influence on the evolution of morphological
      size and shape disparity in monitor lizards.

PMID- 21884064
TI  - Collateral damage: rapid exposure-induced evolution of pesticide resistance leads
      to increased susceptibility to parasites.
AB  - Although natural populations may evolve resistance to anthropogenic stressors
      such as pollutants, this evolved resistance may carry costs. Using an
      experimental evolution approach, we exposed different Daphnia magna populations
      in outdoor containers to the carbamate pesticide carbaryl and control conditions,
      and assessed the resulting populations for both their resistance to carbaryl as
      well as their susceptibility to infection by the widespread bacterial
      microparasite Pasteuria ramosa. Our results show that carbaryl selection led to
      rapid evolution of carbaryl resistance with seemingly no cost when assessed in a
      benign environment. However, carbaryl-resistant populations were more susceptible
      to parasite infection than control populations. Exposure to both stressors
      reveals a synergistic effect on sterilization rate by P. ramosa, but this
      synergism did not evolve under pesticide selection. Assessing costs of rapid
      adaptive evolution to anthropogenic stress in a semi-natural context may be
      crucial to avoid too optimistic predictions for the fitness of the evolving
      populations.

PMID- 21884065
TI  - Protection first then facilitation: a manipulative parasite modulates the
      vulnerability to predation of its intermediate host according to its own
      developmental stage.
AB  - Many trophically transmitted parasites with complex life cycles manipulate their
      intermediate host behavior in ways facilitating their transmission to final host
      by predation. This facilitation generally results from lowering host's
      antipredatory defenses when the parasite is infective to the final host. However,
      a recent theoretical model predicts that an optimal parasitic strategy would be
      to protect the intermediate host from predation when noninfective, before
      switching to facilitation when the infective stage is reached. We tested this
      hypothesis in the fish acanthocephalan parasite Pomphorhynchus laevis using the
      amphipod Gammarus pulex as intermediate host. Gammarids parasitized by
      noninfective stage of P. laevis (acanthella) hid significantly more under refuges
      than uninfected ones. In addition, acanthella-infected gammarids were less
      predated upon by trout than uninfected ones. As predicted, a switch toward
      decreased antipredatory behavior of G. pulex and enhanced vulnerability to
      predation was found when P. laevis reached the stage infective to its final host.
      The parasites appear to be able to exploit plasticity in host antipredatory
      responses, and shift the host optimal response toward their own optimal balance.

PMID- 21884066
TI  - No evidence for postcopulatory inbreeding avoidance in Drosophila melanogaster.
AB  - Selection to avoid inbreeding is predicted to vary across species due to
      differences in population structure and reproductive biology. Over the past
      decade, there have been numerous investigations of postcopulatory inbreeding
      avoidance, a phenomenon that first requires discrimination of mate (or sperm)
      relatedness and then requires mechanisms of male ejaculate tailoring and/or
      cryptic female choice to avoid kin. The number of studies that have found a
      negative association between male-female genetic relatedness and competitive
      fertilization success is roughly equal to the number of studies that have not
      found such a relationship. In the former case, the underlying mechanisms are
      largely unknown. The present study was undertaken to verify and expand upon a
      previous report of postcopulatory inbreeding avoidance in D. melanogaster, as
      well as to resolve underlying mechanisms of inbreeding avoidance using transgenic
      flies that express a sperm head-specific fluorescent tag. However, siblings did
      not have a lower fertilization success as compared to unrelated males in either
      the first (P(1) ) or second (P(2) ) mate role in sperm competition with a
      standard unrelated competitor male in our study population of D. melanogaster.
      Analyses of mating latency, copulation duration, egg production rate, and
      remating interval further revealed no evidence for inbreeding avoidance.

PMID- 21884068
TI  - Increased floral divergence in sympatric monkeyflowers.
AB  - Sympatric sister species are predicted to have greater divergence in reproductive
      traits than allopatric sister species, especially if mating system shifts, such
      as the evolution of self-fertilization, are more likely to originate within the
      geographic range of the outcrossing ancestor. We present evidence that supports
      this expectation-sympatric sister species in the monkeyflower genus, Mimulus,
      exhibit greater divergence in flower size than allopatric sister species.
      Additionally, we find that sympatric sister species are more likely to have one
      species with anthers that overtop their stigmas than allopatric sister species,
      suggesting that the evolution of automatic self-pollination may contribute to
      this pattern. Potential mechanisms underlying this pattern include reinforcement
      and a stepping stone model of parapatric speciation.

PMID- 21884069
TI  - Use of exotic hosts by Lepidoptera: widespread species colonize more novel hosts.
AB  - The study of host shifts by herbivorous insects has played an important role in
      evolutionary biology, contributing to research in coevolution, ecological
      speciation, and adaptive radiation. As invasive plants become more abundant in
      many ecosystems, the potential for exotic host use by native insects increases.
      Graves and Shapiro (2003) have documented exotic host use by 34% of Californian
      butterflies, suggesting that the plants and butterflies of California might be an
      important model system for the colonization and utilization of novel resources.
      In this study, we analyze relationships among geographic range, native diet
      breadth, and the use of exotic hosts by Californian butterflies and skippers
      (Lepidoptera). Geographic range and, to a lesser extent, native diet breadth are
      significant predictors of exotic host use, with positive relationships found both
      before and after phylogenetic correction. These results give insight into the
      process of insect host range evolution, as geographically widespread generalists
      have an apparently greater tendency to use novel, exotic hosts than
      geographically constrained specialists. Increasing occurrences of exotic host use
      are expected and those species not capable of shifting to nonnative hosts are
      likely to have higher vulnerability to extirpation and extinction in the future.

PMID- 21884067
TI  - Nonadaptive evolution of mitochondrial genome size.
AB  - Genomes vary greatly in size and complexity, and identifying the evolutionary
      forces that have generated this variation remains a major goal in biology. A
      controversial proposal is that most changes in genome size are initially
      deleterious and therefore are linked to episodes of decrease in effective
      population sizes. Support for this hypothesis comes from large-scale comparative
      analyses, but vanishes when phylogenetic nonindependence is taken into account.
      Another approach to test this hypothesis involves analyzing sequence evolution
      among clades where duplications have recently fixed. Here we show that episodes
      of fixation of duplications in mitochondrial genomes of the gecko Heteronotia
      binoei (two independent clades) and of mantellid frogs (five distinct branches)
      coincide with reductions in the ability of selection to purge slightly
      deleterious mutations. Our results support the idea that genome complexity can
      arise through nonadaptive processes in tetrapods.

PMID- 21884070
TI  - The evolution of Family Process: contexts and transformations(1) ,(2).

PMID- 21884071
TI  - Couple therapy research and the practice of couple therapy: can we talk?
AB  - As has been true in every other realm of psychotherapy, couple therapy research
      generally has had very little impact on the day-to-day practice of couple
      therapists. To a significant degree, this unfortunate disconnection may be
      attributable to an overemphasis by researchers in the field on treatment packages
      and therapeutic methods/techniques. Insufficient attention has been paid to other
      important sources of influence on treatment outcomes, especially the couple
      therapist herself/himself. It is argued that effective couple therapy requires a
      good "fit" between the person of the therapist and her primary theoretical
      orientation, and that couple therapists may be more influenced by research that
      addresses process aspects of the therapeutic approaches to which they have their
      primary theoretical allegiances.

PMID- 21884072
TI  - Integrative problem-centered metaframeworks therapy I: core concepts and
      hypothesizing.
AB  - Over the last 20 years psychotherapy and family therapy have been inundated with
      a plethora of empirically validated treatments for particular disorders. That
      trend will increase. Psychotherapists will increasingly be exhorted and
      ultimately required to integrate empirical data and multicultural competence into
      their practice. Additionally, individual psychotherapy's default dominance of
      psychotherapeutic discourse needs to integrate and come to theoretical and
      clinical terms with the implications of the growing body of research
      demonstrating the validity and value of a multisystemic perspective. This article
      (and its companion article) presents a comprehensive, integrative, multisystemic,
      and empirically informed psychotherapeutic perspective to help therapists and
      psychotherapy trainers successfully address these challenges-Integrative Problem
      Centered Metaframeworks (IPCM) Therapy. This first article presents and
      illustrates IPCM's theoretical foundation, core concepts, and "case formulating"
      components. It delineates a Blueprint for the practice and teaching of 21st
      century psychotherapists who can meld science and art into best practice.

PMID- 21884073
TI  - Integrative problem-centered metaframeworks therapy II: planning, conversing, and
      reading feedback.
AB  - This is the second of 2 articles presenting Integrative Problem Centered
      Metaframeworks (IPCM) Therapy, a multisystemic, integrative, empirically
      informed, and common factor perspective for family, couple, and individual
      psychotherapy. The first article presented IPCM's foundation concepts and
      Blueprint for therapy, focusing on the first Blueprint component-Hypothesizing or
      assessment. This article, focusing on intervention, presents the other 3
      Blueprint components-Planning, Conversing, and Feedback. Articulated through the
      Blueprint, intervention is a clinical experimental process in which therapists
      formulate hypotheses about the set of constraints (the Web) within a client
      system that prevents problem resolution, develop a therapeutic Plan based on
      those hypotheses, implement the Plan through a coconstructed dialogue with the
      clients, and then evaluate the results. If the intervention is not successful,
      the results become feedback to modify the Web, revise the Plan, and intervene
      again. Guided by the therapeutic alliance, this process repeats until the
      presenting problems resolve. IPCM Planning sequentially integrates the major
      empirically and yet-to-be empirically validated therapies and organizes their key
      strategies and techniques as common factors. Conversing and Feedback employ
      empirical STIC((r)) (Systemic Therapy Inventory of Change) data collaboratively
      with clients to formulate hypotheses and evaluate interventions. This article
      emphasizes the art and science of IPCM practice.

PMID- 21884074
TI  - Facilitating relational empowerment in couple therapy.
AB  - Couples in distressed relationships often get caught up in power struggles,
      "Power Over" interactions that are informed by both neurobiology (e.g., the fight
      flight reaction) and by cultural assumptions (e.g., competition, individualism,
      and patriarchy). This article seeks to widen the discourse about power by
      highlighting "Power To" and "Power With." Power To includes the ability to self
      regulate, to read and manage one's own emotions, and to have voice while
      respecting the other's voice. Power With reflects the couple's commitment to
      conurture the relationship through empathy, respect, and generosity. Power To and
      Power With are proposed to constitute relational empowerment, the ability to
      navigate one's inner world and the interpersonal realm. The neurobiology of both
      couples' reactivity and relational empowerment are considered. Techniques are
      offered to facilitate Power To and Power With, interventions that interrupt
      couples' cycles of reactivity and allow them to make more thoughtful choices.
      Emotion regulation and empathy are particularly important skills of relational
      empowerment, and examples are offered to increase these capacities in couple
      therapy. The therapeutic perspective offered in this article challenges cultural
      practices and assumptions that keep intimate partners polarized in power
      struggles, and explores how relational empowerment can foster an egalitarian,
      mutually respectful relationship.

PMID- 21884075
TI  - Heterosexual, lesbian, and gay male relationships: a comparison of couples in
      1975 and 2000.
AB  - This study examined the differences among lesbians, gay men, and heterosexuals at
      two points in time (1975 and 2000) using responses of 6,864 participants from two
      archival data sets. Groups were compared on variables representing equality of
      behaviors between partners in seven realms: traditionally "feminine" housework,
      traditionally "masculine" housework, finances, support, communication,
      requesting/refusing sex, and decision-making. In addition, the current study
      compared monogamy agreements and monogamy behaviors reported by the two cohorts
      of couple types. Overall, the results indicate that on the equality variables,
      there have been many statistically significant behavioral shifts among the
      different sexual orientations across 25 years. In addition, all couple types
      reported substantially greater rates of monogamy in the year 2000 than in 1975.
      The present study has important clinical implications for therapists working with
      couples because it provides new baseline evidence regarding how couples now
      interact with one another (especially about monogamy) and how this has shifted
      over time. In addition, it elucidates the differences that still exist between
      different couple types, which could serve to inform couple therapists as they
      strive to become more culturally competent working with same-sex couples.

PMID- 21884076
TI  - Guidelines for classifying evidence-based treatments in couple and family
      therapy.
AB  - Guidelines for Evidence-Based Treatments in Family Therapy are intended to help
      guide clinicians, researchers, and policy makers in identifying specific clinical
      interventions and treatment programs for couples and families that have
      scientifically based evidence to support their efficacy. In contrast to criteria,
      which simply identify treatments that "work" and have been employed in the
      evaluation of other psychotherapies, these guidelines propose a three-tiered
      levels-of-evidence-based model that moves from "evidence-informed," to "evidence
      based," to "evidence-based and ready for dissemination and transportation within
      diverse community settings." Each level reflects an interaction between the
      specificity of the intervention, the strength and readth of the outcomes, and the
      quality of the studies that form the evidence. These guidelines uniquely promote
      a clinically based "matrix" approach in which the empirical support is evaluated
      according to various dimensions including strength of the outcomes, the
      applicability across cultural contexts, and demonstration of specific change
      mechanisms. The guidelines are offered not only as a basis for understanding the
      evidence for diverse clinical approaches in couple and family therapy within the
      systemic tradition of the field, but also as an alternative aspirational model
      for evaluating all psychotherapies.

PMID- 21884077
TI  - Multiple family groups for adult cancer survivors and their families: a 1-day
      workshop model.
AB  - With marked advances in early detection and aggressive multimodality treatment,
      many adult cancers are now associated with good prognoses for disease-free
      survival. A burgeoning literature examining posttreatment quality-of-life issues
      has highlighted the numerous challenges experienced by patients and families in
      the aftermath of cancer treatment, further underscoring a need for new family
      based psychosocial support interventions for cancer survivors and their families.
      This paper describes the clinical protocol for one such intervention, a 1-day
      "workshop" version of a multiple family group (MFG) for head and neck cancer
      survivors and their families. Data are reported from our experiences in running
      five 1-day workshops. Families uniformly reported that they were highly satisfied
      with their MFG participation, leading us to conclude that the abbreviated 1-day
      MFG model we are advocating is a promising family-focused support intervention
      for cancer survivors and their families.

PMID- 21884079
TI  - Lessons learned from the landmark "a civil action" trial.

PMID- 21884078
TI  - Developing preventive mental health interventions for refugee families in
      resettlement.
AB  - In refugee resettlement, positive psychosocial outcomes for youth and adults
      depend to a great extent on their families. Yet refugee families find few
      empirically based services geared toward them. Preventive mental health
      interventions that aim to stop, lessen, or delay possible negative individual
      mental health and behavioral sequelae through improving family and community
      protective resources in resettled refugee families are needed. This paper
      describes 8 characteristics that preventive mental health interventions should
      address to meet the needs of refugee families, including: Feasibility,
      Acceptability, Culturally Tailored, Multilevel, Time Focused, Prosaicness,
      Effectiveness, and Adaptability. To address these 8 characteristics in the
      complex environment of refugee resettlement requires modifying the process of
      developmental research through incorporating innovative mental health services
      research strategies, including: resilience framework, community collaboration,
      mixed methods with focused ethnography, and the comprehensive dynamic trial. A
      preventive intervention development cycle for refugee families is proposed based
      on a program of research on refugees and migrants using these services research
      strategies. Furthering preventive mental health for refugee families also
      requires new policy directives, multisystemic partnerships, and research
      training.

PMID- 21884080
TI  - Differences in the personality profile of medication-overuse headache sufferers
      and drug addict patients: a comparative study using MMPI-2.
AB  - BACKGROUND: Medication-overuse headache (MOH) refers to headache attributed to
      excessive use of acute medications. The role of personality needs studies to
      explain the shifting from drug use to drug abuse. The main aim of this study is
      to study personality, according to Minnesota Multiphasic Personality Inventory,
      comparing MOH, episodic headache, substance addicts (SA) vs healthy controls.
      METHODS: Eighty-two MOH patients (mean age 44.5; 20 M, 62 F) and 35 episodic
      headache (mean age 40.2; 8 M, 27 F), were compared to 37 SA (mean age 32.5; 29 M,
      8 F) and 37 healthy controls (mean age: 32.49; 20 M, 17 F). International
      Classification of Headache Disorders 2nd Edition criteria were employed. Chi
      square test, Kruskal-Wallis test, and post hoc comparisons were used for
      statistics. RESULTS: MOH patients scored higher on Hypochondriasis, Depression
      (only females), Hysteria (only females) (P < .000). MOH did not show higher
      scores than episodic headache or healthy controls in dependency scales, while SA
      did. CONCLUSION: The data obtained show that MOH and SA do not share common
      personality characteristics linked to dependence. Although further studies are
      needed to understand if such a difference is related to instrumental
      characteristics or to yet undiscovered psychobiological characteristics of MOH
      patients; however, we hypothesize that the detected difference may rely on the
      fact that drug dependence in the 2 groups is promoted by entirely different
      needs: pleasure seeking in the SA group, pain avoidance in the MOH group.

PMID- 21884081
TI  - Delayed diagnosis in pediatric headache: an outpatient Italian survey.
AB  - OBJECTIVE: The aim of this prospective study is to assess the time lapse between
      the onset of recurring headache and the correct diagnosis in a cohort of
      pediatric patients attending an Italian children's headache center for the first
      time. METHODS: One hundred and one patients and parents, referred to the
      Pediatric Headache Centre of San Raffaele Hospital in Milan, Italy, underwent a
      semi-structured interview to ascertain features of headache since onset (clinical
      and family history, presence of childhood periodic syndromes, previously
      undergone instrumental exams and specialists' examinations before the correct
      diagnosis, past and current treatment). All patients were evaluated by expert
      neurologists and their headache was classified according to the International
      Classification of Headache Disorders II (2004). RESULTS: The median time delay
      from the onset of the first episode of recurrent headache to definite diagnosis
      was 20 months (interquartile range 12 to 36 months). A correlation with younger
      age and a more delayed headache diagnosis was found (r Spearman = 0.25; P =
      .039). An association between diagnostic delay and positive family history
      (median 24 months [12 to 48] vs 12 [6 to 24]; P = .014) or female gender (median
      18 months [12 to 42] vs. 12 [5 to 30]; P trend = .070) was also evident. Notably,
      76 out of 101 patients referred to our Center received an appropriate diagnosis
      according to International Classification of Headache Disorders II at the time of
      our visit only. Of note, up to 21% of this group were previously misdiagnosed
      (for epilepsy 43%, sinusitis 38%, or other diseases 19%), a fact that contributed
      to a longer time of clinical assessment (median 39 months) before reaching a
      correct diagnosis. The other group of 80 patients (79%) did not receive a
      specific diagnosis and treatment, and were not studied until their symptom became
      chronic and disabling. CONCLUSION: Pediatric headache is still under-diagnosed
      and not adequately considered as a health problem in the medical community as
      well as social settings. There is a need for educational programs regarding
      headache involving not only general practitioners, pediatricians, and
      neurologists, but also the general population. These are desirable in order to
      raise awareness of such a condition and, accordingly, treat children accurately.

PMID- 21884082
TI  - Headache due to a large parasitic cyst.

PMID- 21884083
TI  - Which patients with headache do not seek medical attention?
AB  - OBJECTIVES: To evaluate why patients do not discuss their headaches with their
      doctors and to compare these patients with those who seek medical assistance for
      headache. METHOD: Cross-sectional study. A total of 200 consecutive patients
      attended by family doctors had their complaints registered. Those with headaches
      were interviewed. A semi-structured questionnaire, Headache Impact Test and
      Hospital Anxiety and Depression Scale were used. RESULTS: Fifty-two percent had
      headaches. Ten percent sought medical assistance for headache, 11% already had
      received some form of medical assistance for headache. There was no association
      between headache disability and seeking a doctor for headache. Patients that did
      not seek a doctor for headache had a higher prevalence of tension-type headache
      (59.6% vs. 22.1%; P < .01), a lower prevalence of migraine with aura (32.3% vs.
      40.5%; P < .01), headache intensity (5.4 vs. 6.8; P = .01) and frequency (4.2 *
      7.4 days/month; P < .01). Fifty-two percent of them needed preventive treatment.
      Most of them did not seek a doctor because their headaches were mild or received
      relief from painkillers. CONCLUSIONS: Patients who did not seek medical
      assistance for headache had more tension-type headache, less migraine with aura,
      lower headache intensity and frequency, but the same headache disability. Most of
      them needed preventive treatment and did not seek doctors because their headache
      was mild or received relief from painkillers.

PMID- 21884084
TI  - Headache in 25 consecutive patients with atrial septal defects before and after
      percutaneous closure--a prospective case series.
AB  - In contrast to patent foramen ovale that is highly prevalent in the general
      population, atrial septal defect (ASD) is a rare congenital heart defect. The
      effect of ASD closure on headache and migraine remains a matter of controversy.
      The objectives of our study were (1) to determine headache prevalence in
      consecutive patients with ASD scheduled for percutaneous closure for cardiologic
      indications, using the International Classification of Headache Disorders and (2)
      to compare headache characteristics before and after closure of ASD. In this
      observational case series no a priori power analysis was performed. Twenty-five
      consecutive patients were prospectively included over 27 months. Median duration
      of follow-up was 12 months [interquartile range 0]. Prevalence of active headache
      seemed to be higher compared with the general population: any headaches 88% (95%
      confidence interval 70-96), migraine without aura 28% (14-48), migraine with aura
      16% (6-35). After ASD closure, we observed a slightly lower headache frequency
      (median frequency 1.0 [2.6] vs. 0.3 [1.5] headaches per month; P = .067). In
      patients with ongoing headaches, a significant decrease in headache intensity
      (median VAS 7 [3] vs. 5 [4]; P = .036) was reported. Three patients reporting
      migraine with aura before the intervention noted no migraine with aura attacks at
      follow-up, 2 of them reported ongoing tension-type headache, 1 migraine without
      aura. In summary, this prospective observational study confirms the high
      prevalence of headache, particularly migraine, in ASD patients and suggests a
      possible small beneficial effect of ASD closure.

PMID- 21884087
TI  - Tolerance to the beneficial effects of prophylactic migraine drugs: a systematic
      review of causes and mechanisms.
AB  - Loss of benefit of a previously effective treatment regimen, also known as
      tolerance, can be an important barrier to the successful preventive treatment of
      migraine. We undertook a systematic review of the literature to identify the
      prevalence and possible mechanisms of drug tolerance in migraine prophylaxis.
      Results demonstrate that the frequency of tolerance to prophylactic migraine
      treatment is unknown, but available data support an estimate that it occurs in 1
      8% of patients receiving prophylaxis. Four broad types of tolerance were
      identified that are likely to be relevant to migraine prophylaxis. These are
      pharmacokinetic, pharmacodynamic, behavioral, and cross tolerance. The mechanisms
      that underlie these types of tolerance determine whether their effects can be
      overcome or minimized. For example, certain forms of tolerance may be affected by
      manipulation of environmental cues associated with drug administration, by the
      order in which drugs are used, and by the concomitant use of other medications.
      Many medications used for migraine prophylaxis exert their effects through the
      endogenous opioid system. The implications of this finding are explored,
      particularly the parallels between medication overuse headache and tolerance to
      migraine prophylaxis. Given the many ways in which tolerance to migraine
      medications may develop, in some ways it is not surprising that migraine
      preventive drugs stop working; it is more surprising that in many cases they do
      not.

PMID- 21884088
TI  - Tolerance and loss of beneficial effect during migraine prophylaxis: clinical
      considerations.
AB  - A familiar situation in migraine treatment is the patient with an initial
      positive response to prophylactic drug therapy who later experiences relapse. The
      goals of this paper are to provide a theoretical framework to help doctors think
      about this problem, to evaluate factors and response patterns that may be
      associated with different causes of relapse, and to suggest clinical strategies
      that may aid in its management. Six key explanations for loss of benefit from
      prophylactic therapy are: (1) pharmacokinetic, pharmacodynamic, and behavioral
      drug tolerance; (2) non-specific or placebo effects; (3) natural variability in
      disease activity; (4) disease progression; (5) inaccurate recall of treatment
      effects; and (6) drug delivery problems. Current options for patients who
      experience loss of benefit from prophylactic therapy include traditional
      techniques such as switching, re-trying, rotating, or combining drugs. Selected
      behavioral and environmental treatment techniques might also be useful. We
      describe a practical, structured approach to evaluation and management of relapse
      with migraine prophylaxis.

PMID- 21884089
TI  - Tolerance to headache medications.

PMID- 21884090
TI  - Herbal medicinal treatment options for headache and migraine.

PMID- 21884093
TI  - Chronos in synchronicity: manifestations of the psychoid reality.
AB  - Jung's most obvious time-related concept is synchronicity. Yet, even though
      'time' is embedded in it (chronos) there has been no systematic treatment of the
      time factor. Jung himself avoided dealing explicitly with the concept of time in
      synchronicity, in spite of its temporal assumptions and implications. In this
      paper the role of time in synchronicity is examined afresh, locating it in the
      context of meaning and relating it to the psychoid archetype. Synchronicity is
      viewed as an expression of the psychoid; the vital parameter for the elucidation
      of this link appears to be time. The author argues that the psychoid rests on
      relative time which Jung deemed transcendent. The existence of two different uses
      of the word 'time' in Jung's opus are emphasized: fixed time that dominates
      consciousness and relative time that exists in the psyche at large. Since
      consciousness cannot grasp the psychoid's temporality it de-relativizes time;
      examples of this 'behaviour' of time can be observed in instances of
      synchronicity. It is thus argued that synchronicity demonstrates by analogy the
      nature of the psychoid archetype. Jung's quaternio, as it developed via his
      communication with Pauli, is also examined in light of the above presented 'time
      theory'.

PMID- 21884094
TI  - Synchronicity and the meaning-making psyche.
AB  - This paper contrasts Jung's account of synchronicity as evidence of an objective
      principle of meaning in Nature with a view that emphasizes human meaning-making.
      All synchronicities generate indicative signs but only where this becomes a
      'living symbol' of a transcendent intentionality at work in a living universe
      does synchronicity generate the kind of symbolic meaning that led Jung to posit
      the existence of a Universal Mind. This is regarded as a form of personal,
      experiential knowledge belonging to the 'imaginal world of meaning'
      characteristic of the 'primordial mind', as opposed to the 'rational world of
      knowledge' in which Jung attempted to present his experiences as if they were
      empirically and publicly verifiable. Whereas rational knowledge depends on a form
      of meaning in which causal chains and logical links are paramount, imaginal
      meaning is generated by forms of congruent correspondence-a feature that
      synchronicity shares with metaphor and symbol-and the creation of narratives by
      means of retroactive organization of its constituent elements.

PMID- 21884095
TI  - Un-thought out metaphysics in analytical psychology: a critique of Jung's
      epistemological basis for psychic reality.
AB  - The author investigates the relation of Kant, Schopenhauer and Heidegger to
      Jung's attempts to formulate theory regarding the epistemological conundrum of
      what can and what cannot be known and what must remain uncertain. Jung's
      ambivalent use and misuse of Kant's division of the world into phenomenal and
      noumenal realms is highlighted in discussion of concepts such as the psychoid
      archetype which he called 'esse in anima' and his use of Schopenhauer's concept
      of 'will' to justify a transcendence of the psyche/soma divide in a postulation
      of a 'psychoid' realm. Finally, the author describes Jung's reaction to
      Heidegger's theories via his assertion that Heidegger's 'pre-given world design'
      was an alternate formulation of his concept of the archetypes. An underlying
      theme of the paper is a critique of Jung's foundationalism which perpetuates the
      myth of an isolated mind. This model of understanding subjectivity is briefly
      contrasted with Heidegger's 'fundamental ontology' which focuses on a non
      Cartesian 'understanding' of the 'presencing of being' in everyday social and
      historical contexts.

PMID- 21884096
TI  - Jung's equation of the ground of being with the ground of psyche.
AB  - The paper amplifies Jung's psychology of ground associated with the culmination
      of the alchemical process in the unus mundus. It argues that Jung and Dorn
      identify the experience of the ground with the experience of divinity as the
      common originary source of individual and totality. It notes the monistic and
      pantheistic implications of the experience and goes on to amplify the experience
      through Eckhart's mediaeval mysticism of ground and Paul Tillich's modern
      philosophical/theological understanding of ground. It concludes that the
      Jung/Dorn psychological understanding of ground supersedes monotheistic
      consciousness. Their vision supports the emergence of a societal myth based on
      the identification of the ground as the source of all divinities and faith in
      them. This source currently urges a mythic consciousness that would surpass its
      past and current concretions and so alleviate the threat that monotheistic
      consciousness in any domain now poses to human survival.

PMID- 21884097
TI  - The interiorizing movement of logical life: reflections on Wolfgang Giegerich.
AB  - The following article is an account of my discovery of and subsequent immersion
      in Wolfgang Giegerich's work. A sampling of his voluminous writings on the soul
      is set out to illustrate how he attempts to penetrate thinkingly into
      psychological phenomena and his claim that this inevitably brings out their
      internal dialectic. The article summarizes his critiques of Jung, Hillman, and
      The Red Book: Liber Novus.

PMID- 21884100
TI  - Whole genome duplication: challenges and considerations associated with sequence
      orthology assignment in Salmoninae.
AB  - To illustrate some of the challenges and considerations in assigning correct
      orthology necessary for any comparative genomic investigation among salmonids,
      sequence data from the non-coding regions of different chromosomes in three
      members of the subfamily Salmoninae, rainbow trout Oncorhynchus mykiss, Atlantic
      salmon Salmo salar and Arctic charr Salvelinus alpinus, were compared. By
      analysing c. 55 distinct loci, corresponding to c. 142 kbp sequence information
      per species, 18 duplicated patterns representative of the two sequential rounds
      of teleost-specific whole genome duplications (i.e. 3R and 4R WGD) were
      identified. Sequence similarities between the 4R paralogues were c. 90%, which
      was slightly lower than those of the 4R orthologues and c. 60% for the 3R
      products. Through careful examination of the sequence data, however, only 14 loci
      could reliably be assigned as true orthologues. Locus-specific trees were
      constructed through maximum parsimony, maximum likelihood and neighbour-joining
      methods and were rooted using the information from a close relative, lake
      whitefish Coregonus clupeaformis. All approaches generated congruent trees
      supporting the {Coregonus [Salmo (Oncorhynchus, Salvelinus)]} topology. The
      general phenotypic characteristics of sequences, however, were highly suggestive
      of the basal position of Oncorhynchus, raising the hypothesis of an accelerated
      rate of nucleotide evolution in this species.

PMID- 21884101
TI  - Stressed mothers - troubled offspring: a study of behavioural maternal effects in
      farmed Salmo salar.
AB  - Mature female Atlantic salmon Salmo salar were given intraperitoneal cortisol
      implants 1 week prior to stripping to examine the influence of simulated maternal
      stress on offspring boldness and social dominance. Behavioural tests originally
      designed to investigate stress responsiveness and coping styles in salmonids
      (i.e. feeding in isolation, dominance tests and acute confinement) were carried
      out on the offspring 1.5 years after hatching. In the feeding test, there were no
      differences between the two treatment groups in total feeding score or number of
      pellets eaten, but offspring from the cortisol-implanted females made more
      unsuccessful feeding attempts than offspring from control females. In dominance
      tests, there was no difference between controls and cortisol-treated fish
      regarding propensity to become socially dominant. A higher proportion of
      individuals with bite marks, however, was observed in the cortisol group when
      compared to controls. Cortisol-treated offspring that gained dominant rank in the
      dominance tests performed more aggressive acts after stable dominance-subordinate
      relationships were established compared to control winners. During acute
      confinement stress, offspring from cortisol-implanted females showed a reduction
      in the proportion of time they were moving compared to the controls. These
      results indicate that the maternal endocrine state at spawning affects several
      aspects of progeny behaviour potentially related to subsequent success and
      survival in farmed S. salar.

PMID- 21884102
TI  - Implantation of cocoa butter reduces egg and hatchling size in Salmo trutta.
AB  - This study demonstrated that, irrespective of hormone type or dose, administering
      cocoa butter implants during egg development affected the growth of female brown
      trout Salmo trutta and reduced the size of their offspring. Cortisol treatment
      also increased adult mortality. Caution is urged in the use of implants for
      studies of maternal hormonal influences on adult fishes and their offspring.

PMID- 21884103
TI  - Ontogenetic changes in location and morphology of chloride cells during early
      life stages of the Nile tilapia Oreochromis niloticus adapted to fresh and
      brackish water.
AB  - Ontogenetic changes in the location, size, density and morphology of chloride
      cells in the Nile tilapia Oreochromis niloticus adapted to fresh and brackish
      water are described using Na(+) /K(+) -ATPase immunohistochemistry, light
      microscopy (LM), scanning electron microscopy (SEM) and confocal scanning laser
      microscopy (CSLM). The pattern of chloride cell distribution changed during
      development under both treatments, with chloride cell density decreasing
      significantly from hatch to 7 days post-hatch, but appearing on the inner
      opercular area at 3 days post-hatch and increasing significantly thereafter (P <
      0.05). Chloride cells were always denser in fresh- than in brackish-water larvae.
      In both treatments, chloride cells located on the outer operculum and tail showed
      a marked increase in size with age, but cells located on the abdominal epithelium
      of the yolk sac and the inner operculum showed a significant decrease in size (P
      < 0.05). Chloride cells from brackish-water adapted larvae from 1 day post-hatch
      onwards were always significantly larger (P < 0.05) than those from freshwater
      adapted larvae. SEM revealed structural differences in chloride cell apical
      morphology according to environmental conditions. There appears to be clearly
      defined temporal staging of the appearance of adaptive mechanisms that confer an
      ability to cope with varying environmental conditions during early development.

PMID- 21884104
TI  - Reproductive biology and implications for management of the painted sweetlips
      Diagramma pictum in the southern Arabian Gulf.
AB  - The reproductive biology of the painted sweetlips Diagramma pictum was determined
      from 487 individuals collected between January and December 2010 in the southern
      Arabian Gulf. There was no evidence of sex change and the combination of
      histological results with the sex composition of the size and age structures
      indicated a gonochoristic sexual pattern. There were peaks in gonado-somatic
      indices for females in March and October with spawning occurring during two
      seasons (April to May and November). The mean size and age at sexual maturity
      (L(m50) and A(m50) ) were 35.7 cm fork length (L(F) ) and 2.9 years for females
      and 26.7 cm L(F) and 0.5 years for males. The maximum recorded age (11 years) and
      small mean size and young age at sexual maturity for males may be a direct result
      of intensive demersal fishing in the southern Arabian Gulf. There was an
      exponential increase in the cumulative reproductive potential with size and a
      linear increase with age for both sexes. The mean L(F) (L(c50) ) at which D.
      pictum became vulnerable to capture was 33.3 cm, which corresponded to only 3 and
      7% of the cumulative reproductive potential of males and females, respectively.
      Size-specific and age-specific reproductive potential indicated that conventional
      regulations that equate the mean size at first capture to sexual maturation are
      unsuitable for the management of D. pictum.

PMID- 21884105
TI  - Genetic population structure of grey mackerel Scomberomorus semifasciatus in
      northern Australia.
AB  - This study used mtDNA sequence and microsatellite markers to elucidate the
      population structure of Scomberomorus semifasciatus collected from 12 widespread
      sampling locations in Australia. Samples (n = 544) were genotyped with nine
      microsatellite loci, and 353 were sequenced for the control (384 bp) and ATPase
      (800 bp) mtDNA gene regions. Combined interpretation of microsatellite and mtDNA
      data identified four genetic stocks of S. semifasciatus: Western Australia, north
      west coast of the Northern Territory, Gulf of Carpentaria and the eastern coast
      of Queensland. Connectivity among stocks across northern Australia from the
      Northern Territory to the eastern coast of Queensland was high (mean F(ST) =
      0.003 for the microsatellite data and Phi(ST) = 0.033 and 0.009 for control
      region and ATPase, respectively) leading to some uncertainty about stock
      boundaries. In contrast, there was a clear genetic break between the stock in
      Western Australia compared to the rest of northern Australia (mean F(ST) = 0.132
      for the microsatellite data and Phi(ST) = 0.135 and 0.188 for control region and
      ATPase, respectively). This indicates a restriction to gene flow possibly
      associated with suboptimal habitat along the Kimberley coast (north Western
      Australia). The appropriate scale of management for this species corresponds to
      the jurisdictions of the three Australian states, except that authorities in
      Queensland and Northern Territory should co-ordinate the management of the Gulf
      of Carpentaria stock.

PMID- 21884106
TI  - Implications of the divergent use of a suite of estuaries by two exploited marine
      fish species.
AB  - Biological characteristics of the marine species King George whiting Sillaginodes
      punctatus and Australian herring Arripis georgianus in three seasonally open
      estuaries (Broke, Irwin and Wilson Inlets), one permanently open estuary (Oyster
      Harbour) and one normally closed estuary (Wellstead Estuary) on the south coast
      of Western Australia have been determined and compared. Sillaginodes punctatus
      enters the seasonally and permanently open estuaries early in life and reaches
      total lengths (L(T)) >280 mm at which it can be legally retained and thus
      contributes to commercial and recreational fisheries in these systems. This
      sillaginid almost invariably emigrates from these estuaries before reaching its
      typical size at maturity (L(T50)) and does not return after spawning in marine
      waters. In contrast, virtually all female A. georgianus (>= 98%) in the three
      seasonally open estuaries and the majority in the normally closed (89.5%) and
      permanently open estuaries (83%) exceeded the L(T50) of this species at maturity,
      reflecting the fact that the nursery areas of this species are predominantly
      located much further to the east. Although adult females of A. georgianus in
      seasonally open and normally closed estuaries had developed mature ovaries by
      autumn, at which time they were prevented from migrating to the sea by closure of
      the estuary mouths, this species did not spawn in those estuaries. The oocytes in
      their ovaries were undergoing extensive atresia, a process that had been
      incipient prior to oocyte maturation. As the adult females of A. georgianus in
      the permanently open Oyster Harbour at this time all possessed resting gonads,
      i.e. their oocytes were all previtellogenic, the adults that were present in that
      estuary earlier and were destined to spawn in autumn must have emigrated from
      that permanently open estuary to their marine spawning areas prior to the onset
      of gonadal recrudescence. The body masses at length of A. georgianus, which were
      almost invariably higher in summer and autumn than in winter and spring, were
      greater in the very productive environments of the seasonally open and normally
      closed estuaries than in the less productive and essentially marine environment
      of Oyster Harbour and coastal marine waters. In general, the same pattern of
      differences between water bodies was exhibited by the growth of A. georgianus and
      by the more restricted data for body mass at L(T) and growth of S. punctatus.
      Despite an increase in anthropogenic activities in Wilson Inlet over the last two
      decades, the growth of both species was very similar to that recorded 20 years
      earlier. The fisheries implications of the results for the two species are
      discussed.

PMID- 21884107
TI  - Stable-isotope analyses reveal the importance of seagrass beds as feeding areas
      for juveniles of the speckled worm eel Myrophis punctatus (Teleostei:
      Ophichthidae) in Florida.
AB  - The feeding habits and habitats of the speckled worm eel Myrophis punctatus were
      studied on the mangrove edge of the Indian River Lagoon (IRL, Florida) using gut
      content and stable-isotope analyses of carbon (delta(13) C) and nitrogen
      (delta(15) N). Four taxa were identified through analyses of gut contents, and
      the index of relative importance suggested that amphipods, microphytobenthos and
      annelids are the most important food sources in the fish's diet. To assess the
      feeding habits of the fish after their recruitment to the IRL, these food sources
      were collected from mangroves and nearby seagrass beds for isotope analyses.
      Stable isotopes constituted a powerful tool for discriminating fish prey items
      from mangroves (mean +/- s.d.delta(13) C = -20.5 +/- 0.60/00) and those from
      seagrass beds (mean +/- s.d.delta(13) C = -16.9 +/- 0.60/00), thus providing good
      evidence of food source origins. The 56 M. punctatus collected [10.0 < total
      length (L(T) ) < 16.2 cm] had average isotopic signatures of delta(13) C = -16.7
      +/- 0.20/00 and delta(15) N = 8.2 +/- 0.10/00. A significant depletion in (13) C
      was observed for larger juveniles (15.0 < L(T) < 16.2 cm), suggesting that they
      found a portion of their food in mangroves. Estimation of the trophic level from
      stable isotopes (T(Liso)) was similar among different size groups of juvenile
      fish (T(Liso) = 3.2-3.5); therefore, M. punctatus was considered a secondary
      consumer, which is consistent with its zoobenthic diet. The concentration
      dependent mixing Stable Isotope Analysis in R (SIAR) model revealed the
      importance of food sources from seagrass beds as carbon sources for all the fish
      collected, with a significant increase in mangrove prey contributions, such as
      annelids, in the diet of larger juveniles. This study highlights the importance
      of seagrass beds as feeding habitats for juveniles of M. punctatus after their
      recruitment to coastal waters.

PMID- 21884108
TI  - Behavioural and physiological responses of brook trout Salvelinus fontinalis to
      midwinter flow reduction in a small ice-free mountain stream.
AB  - This study presents an experimental analysis of the effects of midwinter flow
      reduction (50-75%, reduction in discharge in 4 h daily pulses) on the physical
      habitat and on behaviour and physiology of overwintering brook trout Salvelinus
      fontinalis in a small mountain stream. Flow reduction did not result in
      significant lowering of temperature or formation of surface or subsurface ice.
      The main findings were (1) daily movement by S. fontinalis increased (c. 2.5
      fold) during flow reduction, but was limited to small-scale relocations (<10 m).
      (2) Undercut banks were the preferred habitat and availability of these habitats
      was reduced during flow reduction. (3) Although both experimental and reference
      fish did lose mass and condition during the experiment, no effects of flow
      reduction on stress indicators (blood cortisol or glucose) or bioenergetics
      (total body fat, water content or mass loss) were detected, probably because
      access to the preferred type of cover remained available. Like other salmonids,
      S. fontinalis moves little and seeks physical cover during winter. Unlike many of
      the more studied salmonids, however, this species overwinters successfully in
      small groundwater-rich streams that often remain ice-free, and this study
      identifies undercut banks as the critical winter habitat rather than substratum
      cover.

PMID- 21884109
TI  - An invasion record for the swimbladder nematode Anguillicoloides crassus in
      European eel Anguilla anguilla in a deep warm-monomictic [corrected] lake, from
      invasion to steady state.
AB  - This study is the first account of the establishment and development of the
      neozoic nematode parasite Anguillicoloides crassus in its host, the European eel
      Anguilla anguilla, in a deep, warm-monomictic [corrected] lake. A 21 year study
      of A. crassus took place in Upper Lake Constance (ULC), Europe's second largest
      pre-alpine lake. The study included two extensive surveys, one in 1991 during the
      initial parasite invasion phase and the second in 2006 when the infection was
      well established. The subtropical swimbladder nematode A. crassus was first
      recorded in A. anguilla in ULC in 1989. Prevalence reached 60% in 1992 and
      remained at this level until 2007. In 2008, prevalence decreased to 48%.
      Infection intensity peaked in 1993 at a mean value of 16 adult parasites per host
      fish. Around 90% of all A. anguilla examined displayed swimbladder lesions, with
      a significant trend to increasing severity over time. Moreover, heavy swimbladder
      lesions were seen in c. 10% of A. anguilla ready to migrate to their spawning
      habitat. Both ruffe Gymnocephalus cernuus and sunfish Lepomis gibbosus serve as
      paratenic hosts for A. crassus in ULC. Gymnocephalus cernuus seems to be the main
      vector, and infection is especially frequent in spring possibly caused by reduced
      immune system efficacy of G. cernuus during winter. In 1991, hypochromic anaemia
      was prevalent in ULC A. anguilla acutely infected with A. crassus, whereas in
      2006 blood values were indicative of chronic infection. The growth and survival
      rates of A. anguilla during their continental phase were not noticeably altered
      in infected fish, but damage to the swimbladder probably impairs migration
      potential and thus the subsequent breeding success of the oceanic phase.

PMID- 21884110
TI  - Molecular cloning, functional characterization and phylogenetic analysis of TRAIL
      in Japanese pufferfish Takifugu rubripes.
AB  - In this study, the complementary DNA (cDNA) of Japanese pufferfish Takifugu
      rubripes tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) was
      cloned by reverse-transcription PCR. The open reading frame of the TRAIL
      consisted of 870 bases. The deduced amino-acid sequence of the TRAIL showed a
      high homology with the sequences of other teleosts. Recombinant soluble TRAIL was
      fused with a small ubiquitin-related modifier gene to enhance the soluble
      expression level in Escherichia coli BL21 (DE3). In vitro, the 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide (MTT) assay indicated that
      the purified soluble TRAIL was able to induce apoptosis of Jurkat and HeLa cells
      in a dose-dependent manner.

PMID- 21884111
TI  - An assessment of the size structure, distribution and behaviour of fish
      populations within a temporarily closed estuary using dual frequency
      identification sonar (DIDSON).
AB  - The fish populations within the East Kleinemonde Estuary, South Africa, were
      studied using Dual frequency IDentification SONar (DIDSON) during March 2010
      which allowed for direct comparisons of the abundance, distribution and behaviour
      of a wide size range of fishes along the length of the system. Small schooling
      fishes <100 mm in total length (L(T) ) were most abundant while larger size
      classes 100-300 and 300-500 mm were less abundant, but evenly distributed
      longitudinally within the estuary. Fishes <100 mm were most abundant within the
      mouth region which may reflect the feeding ecology of species that fall into
      these size classes and the effects of higher turbidities further up the estuary.
      Large fishes >500 mm were similarly most abundant near the mouth, and fishes of
      this size being mostly piscivorous, probably showed these distribution patterns
      due to the location of smaller prey fishes. Differential behaviour was observed
      among the longitudinal sections, with small fishes forming schools in areas of
      low turbidity and particularly in the presence of large predatory fishes. Results
      from this study present a snap-shot of the composition, distribution and
      behaviour of the ichthyofauna within a small temporarily closed estuary, and also
      show that abiotic factors and interactions of various size classes can influence
      their distribution. There is significant potential for DIDSON in future
      ecological research within these systems.

PMID- 21884112
TI  - Shyness and boldness differences across contexts in juvenile three-spined
      stickleback Gasterosteus aculeatus from an anadromous population.
AB  - To examine if a behavioural syndrome is present in juvenile three-spined
      stickleback Gasterosteus aculeatus from anadromous populations, individuals were
      repeatedly exposed to a variety of conditions to assess behavioural consistency
      and determine if a shyness-boldness syndrome occurred. The degree of exploration
      in a novel environment was positively correlated with boldness in all other test
      conditions. Activity level in all contexts, foraging, predator inspection and
      shoaling were found to be repeatable while other behaviours such as latency to
      respond appeared more plastic. Both similarities and differences were found for
      behavioural correlations within and across contexts when compared to prior
      studies on freshwater populations of G. aculeatus. This suggests that selection
      pressures may vary across ontogeny and environments.

PMID- 21884113
TI  - Temperature dependence of cardiac sarcoplasmic reticulum Ca2+-ATPase from rainbow
      trout Oncorhynchus mykiss.
AB  - In this work, the temperature dependence of the sarco-endoplasmic reticulum
      Ca(2+) -ATPase (SERCA2) activity from rainbow trout Oncorhynchus mykiss cardiac
      ventricles was measured and compared with the mammalian SERCA2 isoform. The rate
      of ATP-dependent Ca(2+) transport catalysed by O. mykiss vesicles was totally
      abolished by thapsigargin and the Ca(2+) ionophore A(23187) . At warm
      temperatures (25 and 30 degrees  C), the SERCA2 from O. mykiss ventricles
      displayed the same rate of Ca(2+) uptake. At 35 degrees  C, the activity of the
      O. mykiss enzyme decreased after 20 min of reaction time. The rate of Ca(2+)
      uptake catalysed by the mammalian SERCA2 was temperature dependent exhibiting its
      maximal activity at 35 degrees  C. In contrast to the rate of Ca(2+) uptake, the
      rate of ATP hydrolysis catalysed by O. mykiss SERCA2 was not significantly
      different at 25 and 35 degrees  C, but the rate of ATP hydrolysis catalysed by
      the rat Rattus norvegicus SERCA2 isoform at 35 degrees  C was two-fold higher
      than at 25 degrees  C. At low temperatures (5 to 20 degrees  C), the rate of
      Ca(2+) uptake from O. mykiss SR was less temperature dependent than the R.
      norvegicus isoform, being able to sustain a high activity even at 5 degrees  C.
      The mean +/-s.e. Q(10) values calculated from 25 to 35 degrees  C for ATP
      hydrolysis were 1.112 +/- 0.026 (n = 3) and 2.759 +/- 0.240 (n = 5) for O. mykiss
      and R. norvegicus, respectively. Taken together, the results show that the O.
      mykiss SERCA2 was not temperature dependent over the 10 to 25 degrees  C
      temperature interval commonly experienced by the animal in vivo. The Q(10) value
      of SERCA2 was significantly lower in O. mykiss than R. norvegicus which may be
      key for cardiac function over the wide environmental temperatures experienced in
      this eurythermal fish.

PMID- 21884114
TI  - A quick, least-invasive, inexpensive and reliable method for sampling Gadus
      morhua postlarvae for genetic analysis.
AB  - The present study describes the successful design and testing of a quick, least
      invasive, reliable and inexpensive sampling procedure for Atlantic cod Gadus
      morhua. This protocol can be easily applied to postlarval fish following a simple
      three-step procedure, without availing of commercial DNA extraction kits, while
      ensuring survival of sampled individuals.

PMID- 21884115
TI  - First record and further description of the Cape hagfish Myxine
      capensis(Myxinidae) off Mozambique, western Indian Ocean.
AB  - The first record of the Cape hagfish Myxine capensis in Mozambican waters is
      reported based on a single 356 mm total length specimen taken by bottom trawl off
      Maputo, 25 degrees  52.9' S; 34 degrees  42.7' E - 25 degrees  54.1' S; 34
      degrees  41.0' E, at depths from 557 to 564 m. This account also represents the
      northernmost record of a hagfish in the western Indian Ocean. Morphometric and
      meristic data are provided and compared with those of 27 specimens (including the
      holotype) caught off Namibia and South Africa.

PMID- 21884116
TI  - Non-lethal measurement of pectoral fin aspect ratio in coral-reef fishes.
AB  - This study describes a novel method for measuring pectoral fin aspect ratio (AR)
      on live coral-reef fishes and tests the method against traditional measurements
      taken from a dissected fin. No significant differences were detected among
      repeated fin measurements, which validates the accuracy (intact v. dissected) and
      precision (repeatability over several days) of fin AR measurements on live
      fishes. One exception highlighted issues that may arise when working with species
      prone to fin damage.

PMID- 21884118
TI  - The forensic sciences: international perspectives, global vision.

PMID- 21884119
TI  - Forensic identification science evidence since Daubert: Part I--A quantitative
      analysis of the exclusion of forensic identification science evidence.
AB  - The U.S. Supreme Court decisions in Daubert v. Merrell Dow Pharmaceuticals Inc.
      and Kumho Tire Co. Ltd. v. Carmichael transformed the way scientific expert
      evidence was reviewed in courts across the United States. To gauge the impact of
      these rulings on the admission of forensic identification evidence, the authors
      analyzed 548 judicial opinions from cases where admission of such evidence was
      challenged. Eighty-one cases (15%) involved exclusion or limitation of
      identification evidence, with 50 (65.7%) of these failing to meet the
      "reliability" threshold. This was largely because of a failure to demonstrate a
      sufficient scientific foundation for either the technique (27 cases) or the
      expert's conclusions (17 cases). The incidence of exclusion/limitation because of
      a lack of demonstrable reliability suggests that there is a continuing need for
      the forensic sciences to pursue research validating their underlying theories and
      techniques of identification to ensure their continued acceptance by the courts.

PMID- 21884122
TI  - Letter to the editor--Guns and homicides in the United States.

PMID- 21884120
TI  - Cannabis profiling based on its elemental composition--is it possible?
AB  - Elemental composition of 85 cannabis samples was established using GF AAS and ICP
      OES methods. The robustness of the method was determined by analyzing eight
      independently prepared replicates from a single cannabis plant. The accuracy of
      the method was established by analyzing four plant certified reference material
      samples. The ability of discriminant analysis using elemental compositions to
      distinguish between fiber cannabis samples collected from four different regions
      of Poland was evaluated. Then, a classification model was developed that
      correctly classified selected samples of known origin. Cannabis samples
      confiscated by law enforcement agencies have also been subjected to discriminant
      analysis. A classification model has been developed for four locations in Poland
      (Bialystok, Koscierzyna, the environs of Skarzysko Kamienna, and Bydgoszcz), to
      help determine where samples of unknown origin could have been grown.

PMID- 21884123
TI  - Commentary on the so-called Spontaneous Human Combustion phenomenon.

PMID- 21884125
TI  - Commentary on: Shields LB, Rolf CM, Davis GJ, Hunsaker JC 3rd. Sudden and
      unexpected death in three cases of Ehlers-Danlos syndrome type IV. J Forensic Sci
      2010;55(6):1641-5.

PMID- 21884131
TI  - Effects of dietary macronutrient distribution on vascular integrity in obesity
      and metabolic syndrome.
AB  - Metabolic syndrome is a condition characterized by a clustering of risk factors
      for cardiovascular disease. Emerging data suggest vascular integrity is disrupted
      in metabolic syndrome. Vascular integrity may be determined using several
      measurements, including pulse wave velocity, augmentation index, and flow
      mediated dilation. Arterial stiffness has become an important clinical indicator
      of cardiovascular disease risk. Several circulating inflammatory peptides also
      impact vascular integrity. The present review examines the efficacy of
      nutritional interventions aimed at improving vascular integrity and reducing
      levels of associated inflammatory peptides in individuals with metabolic
      syndrome, with a specific focus on the effect of dietary macronutrient
      redistribution on these factors.

PMID- 21884132
TI  - Prevalence of malnutrition in Parkinson's disease: a systematic review.
AB  - Parkinson's disease (PD) patients may be at higher risk of malnutrition because
      of the symptoms associated with the disease and the side effects of the
      medication used to manage it. A decline in nutritional status is associated with
      many adverse outcomes related to health and quality of life. It is not clear,
      however, to what extent this population is currently affected by malnutrition.
      The objective of this review was to systematically assess the methodology and
      outcomes of studies reporting the prevalence of malnutrition in PD patients.
      Studies that attempted to classify participants with PD into nutritional risk
      and/or malnutrition categories using body mass index, weight change,
      anthropometric measures, and nutritional screening and assessment scores were
      included. The prevalence of malnutrition ranged from 0% to 24% in PD patients,
      while 3-60% of PD patients were reported to be at risk of malnutrition. There was
      a large degree of variation among studies in the methods chosen, the definition
      of malnutrition using those methods, and the detail in which the methodological
      protocols were reported. The true extent of malnutrition in the PD population has
      yet to be accurately quantified. It is important, however, to screen for
      malnutrition at the time of PD diagnosis.

PMID- 21884130
TI  - Balancing the benefits of n-3 polyunsaturated fatty acids and the risks of
      methylmercury exposure from fish consumption.
AB  - Fish and shellfish are widely available foods that provide important nutrients,
      particularly n-3 polyunsaturated fatty acids (n-3 PUFAs), to many populations
      globally. These nutrients, especially docosahexaenoic acid, confer benefits to
      brain and visual system development in infants and reduce risks of certain forms
      of heart disease in adults. However, fish and shellfish can also be a major
      source of methylmercury (MeHg), a known neurotoxicant that is particularly
      harmful to fetal brain development. This review documents the latest knowledge on
      the risks and benefits of seafood consumption for perinatal development of
      infants. It is possible to choose fish species that are both high in n-3 PUFAs
      and low in MeHg. A framework for providing dietary advice for women of
      childbearing age on how to maximize the dietary intake of n-3 PUFAs while
      minimizing MeHg exposures is suggested.

PMID- 21884133
TI  - Economic analysis of nutrition interventions for chronic disease prevention:
      methods, research, and policy.
AB  - Increased interest in the potential societal benefit of incorporating health
      economics as a part of clinical translational science, particularly nutrition
      interventions, led the Office of Dietary Supplements at the National Institutes
      of Health to sponsor a conference to address key questions about the economic
      analysis of nutrition interventions to enhance communication among health
      economic methodologists, researchers, reimbursement policy makers, and
      regulators. Issues discussed included the state of the science, such as what
      health economic methods are currently used to judge the burden of illness,
      interventions, or healthcare policies, and what new research methodologies are
      available or needed to address knowledge and methodological gaps or barriers.
      Research applications included existing evidence-based health economic research
      activities in nutrition that are ongoing or planned at federal agencies.
      International and US regulatory, policy, and clinical practice perspectives
      included a discussion of how research results can help regulators and policy
      makers within government make nutrition policy decisions, and how economics
      affects clinical guideline development.

PMID- 21884134
TI  - Supplemental dietary leucine and the skeletal muscle anabolic response to
      essential amino acids.
AB  - Skeletal muscle protein synthesis (MPS) is regulated by a number of dietary
      factors, to include essential amino acids (EAAs). Leucine, a branched-chain amino
      acid, has been identified as a stimulator of MPS in many cell culture and animal
      studies. However, whether supplemental leucine exerts a unique stimulatory
      effect, as compared to other EAAs, on muscle anabolism in humans has not been
      clearly demonstrated. A recent study found no improvement in resting MPS in
      adults who consumed a 10 g EAA supplement providing added leucine (3.5 g leucine)
      when compared to a control 10 g EAA supplement (1.8 g leucine). These findings
      suggest that added leucine is unnecessary for the stimulation of MPS when
      sufficient EAAs are provided; however, the study of supplemental leucine during
      conditions such as endurance exercise, caloric deprivation, and ageing may be
      warranted.

PMID- 21884135
TI  - Nutrition updates.

PMID- 21884136
TI  - Photochemistry and Photobiology. Editorial.

PMID- 21884137
TI  - Guest editorial.

PMID- 21884138
TI  - The treatment of oral cancer: an overview for dental professionals.
AB  - Oral cancer is a serious life-threatening disease. Dental professionals may be
      the first individuals to identify/suspect these lesions before referring to oral
      and maxillofacial surgeons and oral medicine specialists. Because the general
      dentist will likely follow on with the patient's future oral health, it is
      important that he or she has a basic understanding of the various treatments
      involved in treating oral malignancies and their respective outcomes. The four
      main modalities discussed in this review include surgery alone, radiotherapy
      alone, surgery with radiotherapy, and chemotherapy with or without surgery and
      radiotherapy. Chemotherapy has become an area of great interest with the
      introduction of new 'targeted therapies' demonstrating promising results in
      conjunction with surgery. Despite these results, the toxicities associated with
      chemotherapy regimens are frequent and can be severe, and therefore may not be
      suitable for all patients. Treatment modalities have improved significantly over
      the decades with overall decreases in recurrence rates, improved disease-free and
      overall survival, and an improved quality of life. Prognosis, however, is still
      ultimately dependent on the clinical stage of the tumour at the initial diagnosis
      with respect to size, depth, extent, and metastasis as recurrence rates and
      survival rates plummet with disease progression.

PMID- 21884139
TI  - Oral cancer and oral erythroplakia: an update and implication for clinicians.
AB  - Despite recent advances in therapy and treatment for oral cancer, survival rates
      are still low. It is generally accepted that oral cancer may arise from
      potentially premalignant disorders. Oral erythroplakia has been identified as the
      one with the highest malignant transformation rates. The aim of this review was
      to provide detailed information on oral cancer and oral erythroplakia. Few data
      are available on oral erythroplakia and there is an urgent need for randomized
      controlled trials. Early detection and diagnosis is still the key to survival
      rates. Dentists and physicians may play an important role in the detection of
      premalignant lesions and therefore improve patients' outcome.

PMID- 21884141
TI  - Diving dentistry: a review of the dental implications of scuba diving.
AB  - In light of the overwhelming popularity of self-contained underwater breathing
      apparatus (SCUBA) diving, general dental practitioners should be prepared to
      address complications arising as a result of diving and to provide patients with
      accurate information. The aim of this article was to introduce the concepts of
      diving medicine and dentistry to the dentist, and to supply the dental
      practitioner with some diagnostic tools as well as treatment guidelines. The
      literature was reviewed to address diving barotrauma (pressure-induced injury
      related to an air space) to the head, face and oral regions, as well as scuba
      mouthpiece-related oral conditions. The relevant conditions for dentists who
      treat divers include diving-associated headache (migraine, tension-type
      headache), barosinusitis and barotitis-media (sinus and middle ear barotrauma,
      respectively), neuropathy, trigeminal (CN V) or facial (CN VII) nerve baroparesis
      (pressure-induced palsy), dental barotrauma (barometric-related tooth injury),
      barodontalgia (barometric-related dental pain), mouthpiece-associated herpes
      infection, pharyngeal gag reflex and temporomandibular joint disorder
      (dysfunction). For each condition, a theoretical description is followed by
      practical recommendations for the dental practitioner for the prevention and
      management of the condition.

PMID- 21884140
TI  - Temporomandibular joint surgery: what does it mean to the dental practitioner?
AB  - A poor appreciation of the role of surgery in the management of temporomandibular
      disorders (TMD) may result in some patients being denied access to appropriate
      care. While surgery is often considered as an option of last resort, there are
      instances where surgery is the definitive and sometimes the only treatment
      option. The aim of this paper was to review the role of temporomandibular joint
      (TMJ) surgery and its place in the treatment armamentarium of temporomandibular
      disorders. Indications, rationale for surgery, risks vs. benefits are discussed
      and complemented with examples of clinical cases treated by the author. All
      dental practitioners should be aware of the benefits of TMJ surgery so that
      patients do not suffer unnecessarily from ongoing non-surgical treatments that
      ultimately prove to be ineffective in the management of their condition.

PMID- 21884142
TI  - Self-reported oral health of a metropolitan homeless population in Australia:
      comparisons with population-level data.
AB  - BACKGROUND: There is limited information on self-perceived oral health of
      homeless populations. This study quantified self-reported oral health among a
      metropolitan homeless adult population and compared against a representative
      sample of the metropolitan adult population obtained from the National Survey of
      Adult Oral Health. METHODS: A total of 248 homeless participants (age range 17-78
      years, 79% male) completed a self-report questionnaire. Data for an age-matched,
      representative sample of metropolitan-dwelling adults were obtained from
      Australia's second National Survey of Adult Oral Health. Percentage responses and
      95% confidence intervals were calculated, with non-overlapping 95% confidence
      intervals used to identify statistically significant differences between the two
      groups. RESULTS: Homeless adults reported poorer oral health than their age
      matched general population counterparts. Twice as many homeless adults reported
      visiting a dentist more than a year ago and that their usual reason for dental
      attendance was for a dental problem. The proportion of homeless adults with a
      perceived need for fillings or extractions was also twice that of their age
      matched general population counterparts. Three times as many homeless adults
      rated their oral health as 'fair' or 'poor'. CONCLUSIONS: A significantly greater
      proportion of homeless adults in an Australian metropolitan location reported
      poorer oral health compared with the general metropolitan adult population.

PMID- 21884143
TI  - Dental attendance of oral and oropharyngeal cancer patients in a public hospital
      in Western Australia.
AB  - BACKGROUND: Dentists have recently seen the introduction of devices which aim to
      facilitate early oral cancer detection, sparking interest in opportunistic oral
      cancer screening. However, concerns have been raised about the lack of regular
      dental attendance amongst high risk individuals. The purpose of this study was to
      obtain information pertaining to dental attendance of oral and oropharyngeal
      cancer patients. METHODS: All records of patients referred to the Oral Medicine
      Clinic at the Oral Health Centre of Western Australia, between January 2005 and
      December 2009, from one major teaching hospital were examined. Information
      extracted included age, gender, smoking status, referral date, tumour type,
      tumour site, disease stage (TNM classification), and information on dental
      attendance. Outcomes measured included time (months) since the patient's last
      dental visit and information concerning regularity of dental attendance. RESULTS:
      No association was found between dental attendance and gender, smoking, disease
      stage or age at diagnosis. Most patients had not visited a dentist in the
      preceding 12 months. The mean date of last dental visit was 5.6 years prior.
      CONCLUSIONS: More should be done in Australia to encourage patients at high risk
      of oral cancer to attend the dentist and undergo annual oral soft tissue
      examination.

PMID- 21884144
TI  - Knowledge and perceptions regarding oral and pharyngeal carcinoma among adult
      dental patients.
AB  - BACKGROUND: The aim of this study was to assess awareness and knowledge of oral
      and pharyngeal carcinoma and risk perception for developing the cancer among
      adult patients attending a major dental centre in Perth. Influence of socio
      demographic factors on awareness, knowledge and perception was ascertained.
      METHODS: A random sample of 120 potential participants over the age of 18 who
      attended the Oral Health Centre of Western Australia between 14 and 18 June 2010
      were invited to participate in the survey. A total of 100 participants completed
      a face-to-face interview guided by a questionnaire. RESULTS: Seventy-two per cent
      of the participants had heard of oral and pharyngeal carcinoma. Sixteen per cent
      knew that both smoking and drinking increased the risk of oral and pharyngeal
      carcinoma and 49% knew at least one sign or symptom of the cancer. Language
      spoken at home, education, and employment influenced cancer awareness and
      knowledge. Sixty-two per cent of the participants considered themselves not at
      risk of developing the cancer. CONCLUSIONS: The findings suggest that knowledge
      concerning oral and pharyngeal carcinoma in the community may be limited and
      educational strategies may be required to improve such knowledge.

PMID- 21884145
TI  - Risk factors and symptoms associated with xerostomia: a cross-sectional study.
AB  - BACKGROUND: The aim of this study was to examine the symptoms and risk factors
      associated with self-reported xerostomia. METHODS: Data were collected from 601
      self-administered questionnaires among dental clinic attendees. Logistic
      regression models to estimate odds ratios and 95% confidence intervals were used
      to investigate the association for exposures of interest, such as socio
      demographic characteristics, self-reported symptoms, oral hygiene habits and
      xerostomia. RESULTS: Participants reported having dry mouth in 19.6% of cases.
      Xerostomia was associated with a significant increase in the odds of having dry
      lips, throat, eye, skin and nose. Patients with self-reported xerostomia were
      three times more likely to drink water to swallow food than were patients without
      xerstomia. Older individuals were significantly more likely to report dry mouth,
      and the prevalence of xerostomia increased with advancing age. The prevalence of
      xerostomia in patients taking one or more drugs was significantly higher compared
      to medication-free patients, and increased with increasing numbers of medications
      used. Finally, individuals with a nervous or mental disorder, or who wore
      removable dentures were five times more likely to develop xerostomia than
      patients without disorder or dentures. CONCLUSIONS: Dentists should be familiar
      with the symptoms of xerostomia and be prepared to take an active role in the
      diagnosis, management and treatment of the oral complications.

PMID- 21884146
TI  - Inhaled methoxyflurane (Penthrox) sedation for third molar extraction: a
      comparison to nitrous oxide sedation.
AB  - BACKGROUND: The aim of this study was to evaluate the use of inhaled
      methoxyflurane (Penthrox) in the reduction of dental anxiety in patients
      undergoing mandibular third molar removal in a specialist surgical suite and
      compare it to the conventional nitrous oxide sedation. METHODS: A prospective
      randomized, non-blinded crossover design study of 20 patients receiving two types
      of sedation for their third molar extraction who participated in 40 treatment
      sessions. At first appointment, a patient was randomly assigned to receive either
      nitrous oxide sedation or intermittent Penthrox inhaler sedation, with the
      alternate regimen administered during the second appointment. Peri-procedural
      vital signs (heart rate and blood pressure) were recorded and any deviations from
      20% from the baseline values, as well as any drop in oxygen saturation below 92%
      were documented. The Ramsay Sedation Scale (RSS) score was recorded every five
      minutes. Patient cooperation during the procedure, patients' general opinion
      about the sedation technique, surgeon satisfaction and the occurrence of side
      effects were all recorded. After the second procedure, the patient was also asked
      if he or she had any preference of one sedation technique over the other.
      RESULTS: Levels of sedation were comparable in nitrous oxide and Penthrox
      sedation sessions. However, at 15 minutes of sedation it was significantly
      lighter (p < 0.05) in Penthrox. No patient in both regimens reached a RSS deeper
      than a score of 4. Parameters measured for assessment of sedation (patient
      cooperation, surgeon satisfaction and patient general opinion about sedation
      technique) were all similarly comparable for both nitrous oxide and Penthrox. In
      both sedation sessions, the odour of the inhalational agent was accepted by the
      patients; half of the patients (10 patients) who received methoxyflurane thought
      its odour was pleasant. Patients preferred methoxyflurane (Penthrox) inhalation
      over nitrous oxide sedation (Fisher's Exact test, p < 0.05). Adverse events were
      minimal. No patient was either deeply sedated or agitated. Blood pressure was
      within +/- 20% from the baseline values. No patient had oxygen saturation less
      than 92%. Dizziness was the most frequently encountered side effect in both
      regimens (four patients each). Two patients had bradycardia (HR < 60
      beats/minute) when nitrous oxide was used in comparison to one patient with
      Penthrox sedation. Paraesthesia of fingers and heaviness of the chest was
      encountered only with nitrous oxide sedation (four patients). Mild self-limited
      shivering occurred in one patient with Penthrox sedation. CONCLUSIONS: The
      Penthrox Inhaler can produce a comparable sedation to that of nitrous oxide for
      the surgical extraction of third molars under local anaesthesia.

PMID- 21884147
TI  - The all-ceramic, inlay supported fixed partial denture. Part 2. Fixed partial
      denture design: a finite element analysis.
AB  - The clinical use of all-ceramic crowns and fixed partial dentures has seen
      widespread adoption over the past few years due to their increasing durability
      and longevity. However, the application of inlays as an abutment design has not
      been as readily embraced because of their relatively high failure rates. With the
      use of an idealized inlay preparation design and prosthesis form which better
      distributes the tensile stresses, it is possible to utilize the inlay as support
      for an all-ceramic fixed partial denture. Utilizing a three-dimensional finite
      element analysis, a direct comparison of the inlay supported all-ceramic bridge
      against the traditional full crown supported all-ceramic bridge is made. The
      results demonstrate that peak stresses in the inlay bridge are around 20% higher
      than in the full crown supported bridge with von Mises peaking at about 730 MPa
      when subjected to theoretical average maximum bite force in the molar region of
      700 N, which is similar to the ultimate tensile strengths of current zirconia
      based ceramics.

PMID- 21884148
TI  - Cardiovascular responses to different stages of restorative dental treatment
      unaffected by local anaesthetic type.
AB  - BACKGROUND: The aim of this study was to evaluate the cardiovascular effects of
      maxillary infiltration using 2% lidocaine with 1:100,000 adrenaline, 4% articaine
      with 1:200,000 adrenaline, and 4% articaine with 1:100,000 adrenaline in
      different stages during restorative dental procedures. METHODS: Twenty healthy
      patients randomly received 1.8 mL of the three local anaesthetics. Systolic blood
      pressure, average blood pressure, diastolic blood pressure, and heart rate were
      evaluated by the oscillometric and photoplethysmograph methods in seven stages
      during the appointment. RESULTS: Statistical analysis by ANOVA and Tukey tests of
      cardiovascular parameters did not show significant differences between the
      anaesthetic associations. There were significant differences for the parameters
      among different clinical stages. CONCLUSIONS: The variation of cardiovascular
      parameters was similar for lidocaine and articaine with both adrenaline
      concentrations and showed no advantage of one drug over the other. Cardiovascular
      parameters were influenced by the stages of the dental procedures, which showed
      the effect of anxiety during restorative dental treatment.

PMID- 21884149
TI  - Effect of supplementation of soft drinks with green tea extract on their erosive
      potential against dentine.
AB  - BACKGROUND: Matrix metalloproteinase (MMP) inhibitors reduce dentine erosion.
      This in vitro study evaluated the effect of the supplementation of soft drinks
      with green tea extract, a natural inhibitor of MMPs, on their erosive potential
      against dentine. METHODS: For each drink tested (Coca-Cola, Kuat guarana, Sprite
      and light Coca-Cola), 40 dentine specimens were divided into two subgroups
      differing with respect to supplementation with green tea extract at 1.2% (OM24,
      100%Camellia sinensis leaf extract, containing 30 +/- 3% of catechin; Omnimedica,
      Switzerland) or not (control). Specimens were subjected to four pH cycles,
      alternating de- and remineralization in one day. For each cycle, samples were
      immersed in pure or supplemented drink (10 minutes, 30 mL per block) and in
      artificial saliva (60 minutes, 30 mL per block) at 37  degrees C, under
      agitation. Dentine alterations were determined by profilometry (MUm). Data were
      analysed by two-way ANOVA and Bonferroni's test (p < 0.05). RESULTS: A
      significant difference was observed among the drinks tested with Sprite leading
      to the highest surface loss and light Coca-Cola to the lowest. Supplementation
      with green tea extract reduced the surface loss by 15% to 40% but the difference
      was significant for Coca-Cola only. CONCLUSIONS: Supplementation of soft drinks
      with green tea extract might be a viable alternative to reduce their erosive
      potential against dentine.

PMID- 21884150
TI  - Oral cancer in young non-habitue females: a report of four cases and review of
      the literature.
AB  - BACKGROUND: The aim of this study is to highlight the growing incidence of oral
      cancer in young females without apparent traditional risk factors. METHODS: We
      present a case series of young female patients with histopathologically diagnosed
      squamous cell carcinoma of the tongue and no known exposure to major risk
      factors, reporting to our institution over one year. A review of the literature
      was carried out to find documented studies on oral cancer in young females.
      RESULTS: We found an increase in the number of young female patients presenting
      with squamous cell carcinomas on the lateral border of the tongue who did not
      have any of the traditional risk factors associated with the disease, which is in
      contrast with the number of male patients presenting with the same disease.
      CONCLUSIONS: Our study highlights the increasing incidence of oral cancer in
      young females without apparent traditional risk factors, an area of growing
      concern. Published studies in this particular group are limited. Nevertheless,
      the situation is alarming owing to the seriousness this problem poses for the
      community. More research is required to determine the aetiological and risk
      factors associated with this outcome.

PMID- 21884151
TI  - Oral plasmablastic lymphoma: a case report.
AB  - Oral plasmablastic lymphoma is a rare malignancy that is associated with patients
      with HIV or other immunosuppression. This article describes a case of a patient
      with severe haemophilia A (<1% factor VIII) who had medically acquired HIV and
      hepatitis C, a CD4+ count of 192 cells/MUL and a viral load of 33 200 copies/mL.
      The patient presented with a two-month history of a firm swelling around a lower
      molar. The tooth was removed and the surrounding tissue biopsied. The importance
      of obtaining an early definitive diagnosis and seeking adequate medical treatment
      is discussed.

PMID- 21884152
TI  - Oral health messages for the Australian public. Findings of a national consensus
      workshop.
AB  - The Australian National Oral Health Plan 2004-2013 noted the importance of oral
      health promotion in improving oral health and stated that broad agreement was
      required on a consistent suite of evidence-based oral health promotion messages.
      Consistent messages are needed to avoid confusion among the public and to assist
      the advocacy for oral health being integrated into general health promotion. A
      workshop was held to examine the scientific evidence and develop consensus oral
      health messages for the Australian public which are in line with the general
      health messages recommended by Australian health authorities.

PMID- 21884157
TI  - Introduction to social neuroscience: gene, environment, brain, body.

PMID- 21884155
TI  - Dental implant tourism.

PMID- 21884158
TI  - Sociophysiology 25 years ago: early perspectives of an emerging discipline now
      part of social neuroscience.
AB  - Sociophysiology was a term used early in the history of sociology and then again
      25 years ago to describe interactions between the "social" and the "biological"
      worlds. Social scientists had largely viewed biology and the brain as a "black
      box" that was not an active aspect of their work or theories. A landmark,
      unpublished conference in 1986 brought together social scientists and biologists
      dedicated to the idea that bringing sociological conceptualizations and
      approaches together with those of physiology might create new ways to understand
      human behavior. The umbrella question for sociophysiology was dual: how do social
      processes impact the physiology of the organism, and how does that altered
      physiology affect future social behavior? This paper summarizes that conference
      with the goal of providing a glimpse into the early history of social
      neuroscience and to demonstrate the variety of individuals and interests that
      were present at the emergence of this new field. The late Patricia R. Barchas
      organized and chaired the conference.

PMID- 21884160
TI  - Metabolic syndrome: links to social stress and socioeconomic status.
AB  - Socioeconomic stress associated with financial and psychosocial stress is
      widespread in society. A comprehensive body of research indicates that low
      socioeconomic status and social stress is associated with a broad spectrum of
      health risks. This paper reviews epidemiological evidence demonstrating the
      association between chronic social stress and development of obesity and symptoms
      leading to metabolic syndrome. The cumulative effects of socioeconomic stress on
      health and well being are evident throughout the lifespan, affecting children,
      adolescents, and adults. While the links between stress and metabolic disease are
      documented, the mechanisms remain less well understood. Animal models are well
      established and have provided opportunities to systematically investigate
      contributing mechanisms that may be targeted to develop treatment and prevention
      strategies against metabolic disorders arising from exposure to chronic social
      stress.

PMID- 21884159
TI  - Sleep quality, social well-being, gender, and inflammation: an integrative
      analysis in a national sample.
AB  - Social isolation and poor sleep quality are independent predictors of poor health
      outcomes and increased biological risk for disease. We previously found in a
      small sample of older women that the presence of social ties compensated for poor
      sleep in associations with the inflammatory protein interleukin 6 (IL-6). The
      current study extended those findings to a national sample of middle-aged and
      older men and women. Using both subjective and objective sleep assessments, we
      found that in men, but not in women, social engagement moderated the association
      of subjective sleep complaints with both IL-6 and the soluble adhesion molecule E
      selectin. Social engagement also moderated the link between sleep efficiency
      assessed by actigraphy-and IL-6 levels in men, but not in women. These results
      extend our previous work and bolster the suggestion that positive psychological
      functioning may compensate for other risk factors in predicting advantageous
      profiles of biological risk in aging adults.

PMID- 21884162
TI  - Extreme marginalization: addiction and other mental health disorders, stigma, and
      imprisonment.
AB  - Major well-defined medical problems that are, in part, the unfortunate outcome of
      a negative social environment may include specific addictive diseases and other
      mental health disorders, in particular the affective disorders of anxiety,
      depression, social phobia, and posttraumatic stress syndrome. This overview
      touches on the topic of extreme marginalization associated with addiction and
      other mental health disorders, along with arrest, imprisonment, and parole. All
      of these are characterized by a lasting stigma that hauntingly continues to
      affect each person suffering from any of these problems.

PMID- 21884161
TI  - Blunted diurnal decline of cortisol among older adults with low socioeconomic
      status.
AB  - Low socioeconomic status (SES) is associated with increased risk for adverse
      health outcomes; those with low SES are thought to experience greater
      environmental disadvantage and exposure to chronic stress over the life course.
      The effects of chronic stress on health have been measured by cortisol levels and
      variations in their diurnal pattern. However, the patterns of association between
      SES and cortisol have been equivocal in older adults. This paper examined in 98
      older adults participating in the Brain Health Substudy of the Baltimore
      Experience Corps Trial baseline patterns of diurnal variation in salivary
      cortisol associated with lower versus higher SES using total income and perceived
      SES relative to others. For each measure, participants stratified into lower
      versus higher SES showed a more blunted rate of decline in diurnal salivary
      cortisol over the day in adjusted models (P values <= 0.05). There were no SES
      related differences in awakening cortisol, cortisol-awakening response, or area
      under the curve. These findings confirm prior evidence of a biologic pathway
      through which socioeconomic disadvantage is linked to biologic vulnerability, and
      through which the impact of volunteer service in Experience Corps may be
      measured.

PMID- 21884163
TI  - Intracellular sensors of microbes and danger.

PMID- 21884164
TI  - Intracellular sensors of extracellular bacteria.
AB  - Initial recognition of bacteria by the innate immune system is thought to occur
      primarily by germline-encoded pattern recognition receptors (PRRs). These
      receptors are present in multiple compartments of host cells and are thus capable
      of surveying both the intracellular and extracellular milieu for bacteria. It has
      generally been presumed that the cellular location of these receptors dictates
      what type of bacteria they respond to: extracellular bacteria being recognized by
      cell surface receptors, such as certain Toll-like receptors, and bacteria that
      are capable of breaching the plasma membrane and entering the cytoplasm, being
      sensed by cytoplasmic receptors, including the Nod-like receptors (NLRs).
      Increasingly, it is becoming apparent that this is a false dichotomy and that
      extracellular bacteria can be sensed by cytoplasmic PRRs and this is crucial for
      controlling the levels of these bacteria. In this review, we discuss the role of
      two NLRs, Nod1 and Nod2, in the recognition of and response to extracellular
      bacteria.

PMID- 21884165
TI  - Two signal models in innate immunity.
AB  - Two-signal models have a rich history in immunology. In the classic two-signal
      model of T-cell activation, signal one consists of engagement of the T-cell
      receptor by antigen/major histocompatibility complex, whereas signal two arises
      from costimulatory ligands on antigen-presenting cells. A requirement for two
      independent signals helps to ensure that T-cell responses are initiated only in
      response to bona fide infectious threats. Our studies have led us to conclude
      that initiation of innate immune responses to pathogens also often requires two
      signals: signal one is initiated by a microbe-derived ligand, such as
      lipopolysaccharide (LPS) or flagellin, whereas signal two conveys additional
      contextual information that often accompanies infectious microbes. Although
      signal one alone is sufficient to initiate many innate responses, certain
      responses-particularly ones with the potential for self-damage-require two
      signals for activation. Many of our studies have employed the intracellular
      bacterial pathogen Legionella pneumophila, which has been established as a
      valuable model for understanding innate immune responses. In this review, we
      discuss how the innate immune system integrates multiple signals to generate an
      effective response to L. pneumophila and other bacterial pathogens.

PMID- 21884166
TI  - Peptidoglycan: a critical activator of the mammalian immune system during
      infection and homeostasis.
AB  - Peptidoglycan is a conserved structural component of the bacterial cell wall with
      molecular motifs unique to bacteria. The mammalian immune system takes advantage
      of these properties and has evolved to recognize this microbial associated
      molecular pattern. Mammals have four secreted peptidoglycan recognition proteins,
      PGLYRP-1-4, as well as two intracellular sensors of peptidoglycan, Nod1 and Nod2.
      Recognition of peptidoglycan is important in initiating and shaping the immune
      response under both homeostatic and infection conditions. During infection,
      peptidoglycan recognition drives both cell-autonomous and whole-organism defense
      responses. Here, we examine recent advances in the understanding of how
      peptidoglycan recognition shapes mammalian immune responses in these diverse
      contexts.

PMID- 21884167
TI  - Recognition of nucleic acids by pattern-recognition receptors and its relevance
      in autoimmunity.
AB  - Host cells trigger signals for innate immune responses upon recognition of
      conserved structures in microbial pathogens. Nucleic acids, which are critical
      components for inheriting genetic information in all species including pathogens,
      are key structures sensed by the innate immune system. The corresponding
      receptors for foreign nucleic acids include members of Toll-like receptors, RIG-I
      like receptors, and intracellular DNA sensors. While nucleic acid recognition by
      these receptors is required for host defense against the pathogen, there is a
      potential risk to the host of self-nucleic acids recognition, thus precipitating
      autoimmune and autoinflammatory diseases. In this review, we discuss the roles of
      nucleic acid-sensing receptors in guarding against pathogen invasion,
      discriminating between self and non-self, and contributing to autoimmunity and
      autoinflammatory diseases.

PMID- 21884169
TI  - RIG-I-like receptors: cytoplasmic sensors for non-self RNA.
AB  - Viral infection results in the generation of non-self RNA species in the cells,
      which is recognized by retinoic acid inducible gene-I-like receptors (RLRs), and
      initiates innate antiviral responses, including the production of proinflammatory
      cytokines and type I interferon. In this review, we summarize reports on virus
      specificity of RLRs, structures of non-self RNA patterns, structural biology of
      RLRs, and the signaling adapter molecules involved in antiviral innate immunity.

PMID- 21884170
TI  - Cytoplasmic DNA innate immune pathways.
AB  - The innate immune system is responsible for detecting microbial invasion of the
      cell and for stimulating host defense countermeasures. These anti-pathogen
      procedures include the transcriptional activation of powerful antiviral genes
      such as the type I interferons (IFNs) or the triggering of inflammatory responses
      through interleukin-1 (IL-1) production. Over the past decade, key cellular
      sensors responsible for triggering innate immune signaling pathways and host
      defense have started to be resolved and include the Toll-like receptor (TLR), RIG
      I-like helicase, and the cytoplasmic nucleotide-binding oligermerization domain
      like receptor families. These sensors recognize non-self pathogen-associated
      molecular patterns such as microbial lipopolysaccharides and nucleic acids. For
      example, TLR9 has evolved to detect CpG DNA commonly found in bacteria and
      viruses and to initiate the production of IFN and other cytokines. In contrast,
      AIM2 (absent in melanoma 2) has been shown to be essential for mediating
      inflammatory responses involving IL-1beta following the sensing of microbial DNA.
      Recently, a molecule referred to as STING (stimulator of IFN genes) was
      demonstrated as being vital for recognizing cytoplasmic DNA and for activating
      the production of innate immune genes in response to a variety of DNA pathogens
      and even certain RNA viruses. Comprehending the mechanisms of intracellular DNA
      mediated innate immune signaling may lead to the design of new adjuvant concepts
      that will facilitate vaccine development and may provide important information
      into the origins of autoimmune disease.

PMID- 21884171
TI  - The PYHIN protein family as mediators of host defenses.
AB  - The innate immune response is the first line of defense against infection and
      relies on the ability of immune cells to detect the presence of infection through
      germline-encoded pattern recognition receptors. These include the Toll-like
      receptors, the retinoic acid inducible gene-like receptors, the nucleotide
      oligomerization domain-like receptors, and a number of DNA-sensing molecules.
      Members of the PYHIN protein family have recently emerged as sensors of microbial
      DNA. PYHIN proteins bind microbial DNA and form caspase-1-activating
      inflammasomes (AIM2) or drive type I IFN gene transcription (IFI16). Here, we
      review these discoveries and highlight the emerging role of the PYHIN protein
      family in mammalian host defenses.

PMID- 21884168
TI  - dsRNA sensors and plasmacytoid dendritic cells in host defense and autoimmunity.
AB  - The innate immune system detects viruses through molecular sensors that trigger
      the production of type I interferons (IFN-I) and inflammatory cytokines. As
      viruses vary tremendously in size, structure, genomic composition, and tissue
      tropism, multiple sensors are required to detect their presence in various cell
      types and tissues. In this review, we summarize current knowledge of the
      diversity, specificity, and signaling pathways downstream of viral sensors and
      ask whether two distinct sensors that recognize the same viral component are
      complementary, compensatory, or simply redundant. We also discuss why viral
      sensors are differentially distributed in distinct cell types and whether a
      particular cell type dominates the IFN-I response during viral infection.
      Finally, we review evidence suggesting that inappropriate signaling through viral
      sensors may induce autoimmunity. The picture emerging from these studies is that
      disparate viral sensors in different cell types form a dynamic and integrated
      molecular network that can be exploited for improving vaccination and therapeutic
      strategies for infectious and autoimmune diseases.

PMID- 21884173
TI  - The inflammasome: an integrated view.
AB  - An inflammasome is a multiprotein complex that serves as a platform for caspase-1
      activation and caspase-1-dependent proteolytic maturation and secretion of
      interleukin-1beta (IL-1beta). Though a number of inflammasomes have been
      described, the NLRP3 inflammasome is the most extensively studied but also the
      most elusive. It is unique in that it responds to numerous physically and
      chemically diverse stimuli. The potent proinflammatory and pyrogenic activities
      of IL-1beta necessitate that inflammasome activity is tightly controlled. To this
      end, a priming step is first required to induce the expression of both NLRP3 and
      proIL-1beta. This event renders the cell competent for NLRP3 inflammasome
      activation and IL-1beta secretion, and it is highly regulated by negative
      feedback loops. Despite the wide array of NLRP3 activators, the actual triggering
      of NLRP3 is controlled by integration a comparatively small number of signals
      that are common to nearly all activators. Minimally, these include potassium
      efflux, elevated levels of reactive oxygen species (ROS), and, for certain
      activators, lysosomal destabilization. Further investigation of how these and
      potentially other as yet uncharacterized signals are integrated by the NLRP3
      inflammasome and the relevance of these biochemical events in vivo should provide
      new insight into the mechanisms of host defense and autoinflammatory conditions.

PMID- 21884172
TI  - Intracellular sensing of microbes and danger signals by the inflammasomes.
AB  - The cells of the innate immune system mobilize a coordinated immune response
      towards invading microbes and after disturbances in tissue homeostasis. These
      immune responses typically lead to infection control and tissue repair.
      Exaggerated or uncontrolled immune responses, however, can also induce acute of
      chronic inflammatory pathologies that are characteristic for many common diseases
      such as sepsis, arthritis, atherosclerosis, or Alzheimer's disease. In recent
      years, the concerted efforts of many scientists have uncovered numerous
      mechanisms by which immune cells detect foreign or changed self-substances that
      appear in infections or during tissue damage. These substances stimulate
      signaling receptors, which leads to cellular activation and the induction of
      effector mechanisms. Here, we review the role of inflammasomes, a family of
      signaling molecules that form multi-molecular signaling platforms and activate
      inflammatory caspases and interleukin-1beta cytokines.

PMID- 21884174
TI  - Sensing damage by the NLRP3 inflammasome.
AB  - The NLRP3 inflammasome is activated in response to a variety of signals that are
      indicative of damage to the host including tissue damage, metabolic stress, and
      infection. Upon activation, the NLRP3 inflammasome serves as a platform for
      activation of the cysteine protease caspase-1, which leads to the processing and
      secretion of the proinflammatory cytokines interleukin-1beta (IL-1beta) and IL
      18. Dysregulated NLRP3 inflammasome activation is associated with both heritable
      and acquired inflammatory diseases. Here, we review new insights into the
      mechanism of NLRP3 inflammasome activation and its role in disease pathogenesis.

PMID- 21884175
TI  - Deregulated inflammasome signaling in disease.
AB  - Inflammasomes are multi-protein complexes that sense microbial molecules and
      endogenous danger signals in intracellular compartments. Inflammasome assembly
      results in caspase-1 activation, which in turn drives maturation and secretion of
      the pro-inflammatory cytokines interleukin 1beta (IL-1beta) and IL-18, and
      induces pyroptosis to eliminate the infectious agent. The importance of
      inflammasomes in regulating immune responses was recognized with the discovery of
      polymorphisms in genes encoding inflammasome components and their linkage to
      aberrant production of IL-1beta and IL-18 in autoimmune and hereditary periodic
      fevers syndromes. We review the current knowledge on the role of inflammasomes in
      regulating innate and adaptive immune responses with an emphasis on the role of
      these immune complexes in autoinflammatory disorders and autoimmune diseases such
      as colitis, type I diabetes, multiple sclerosis and vitiligo.

PMID- 21884176
TI  - Molecular mechanisms of inflammasome activation during microbial infections.
AB  - The innate immune system plays a crucial role in the rapid recognition and
      elimination of invading microbes. Detection of microbes relies on germ-line
      encoded pattern recognition receptors (PRRs) that recognize essential bacterial
      molecules, so-called pathogen-associated molecular patterns (PAMPs). A subset of
      PRRs, belonging to the NOD-like receptor (NLR) and the PYHIN protein families,
      detects viral and bacterial pathogens in the cytosol of host cells and induces
      the assembly of a multi-protein signaling platform called the inflammasome. The
      inflammasome serves as an activation platform for the mammalian cysteine protease
      caspase-1, a central mediator of innate immunity. Active caspase-1 promotes the
      maturation and release of interleukin-1beta (IL-1beta) and IL-18 as well as
      protein involved in cytoprotection and tissue repair. In addition, caspase-1
      initiates a novel form of cell death called pyroptosis. Here, we discuss latest
      advances and our insights on inflammasome stimulation by two model intracellular
      pathogens, Francisella tularensis and Salmonella typhimurium. Recent studies on
      these pathogens have significantly shaped our understanding of the molecular
      mechanisms of inflammasome activation and how microbes can evade or manipulate
      inflammasome activity. In addition, we review the role of the inflammasome
      adapter ASC in caspase-1 autoproteolysis and new insights into the structure of
      the inflammasome complex.

PMID- 21884177
TI  - Innate and adaptive immune responses to cell death.
AB  - The immune system plays an essential role in protecting the host against
      infections and to accomplish this task has evolved mechanisms to recognize
      microbes and destroy them. In addition, it monitors the health of cells and
      responds to ones that have been injured and killed, even if this occurs under
      sterile conditions. This process is initiated when dying cells expose
      intracellular molecules that can be recognized by cells of the innate immune
      system. As a consequence of this recognition, dendritic cells are activated in
      ways that help to promote T-cell responses to antigens associated with the dying
      cells. In addition, macrophages are stimulated to produce the cytokine
      interleukin-1 that then acts on radioresistant parenchymal cells in the host in
      ways that drive a robust inflammatory response. In addition to dead cells, a
      number of other sterile particles and altered physiological states can similarly
      stimulate an inflammatory response and do so through common pathways involving
      the inflammasome and interleukin-1. These pathways underlie the pathogenesis of a
      number of diseases.

PMID- 21884178
TI  - Caspase-1-induced pyroptotic cell death.
AB  - Programmed cell death is a necessary part of development and tissue homeostasis
      enabling the removal of unwanted cells. In the setting of infectious disease,
      cells that have been commandeered by microbial pathogens become detrimental to
      the host. When macrophages and dendritic cells are compromised in this way, they
      can be lysed by pyroptosis, a cell death mechanism that is distinct from
      apoptosis and oncosis/necrosis. Pyroptosis is triggered by Caspase-1 after its
      activation by various inflammasomes and results in lysis of the affected cell.
      Both pyroptosis and apoptosis are programmed cell death mechanisms but are
      dependent on different caspases, unlike oncosis. Similar to oncosis and unlike
      apoptosis, pyroptosis results in cellular lysis and release of the cytosolic
      contents to the extracellular space. This event is predicted to be inherently
      inflammatory and coincides with interleukin-1beta (IL-1beta) and IL-18 secretion.
      We discuss the role of distinct inflammasomes, including NLRC4, NLRP3, and AIM2,
      as well as the role of the ASC focus in Caspase-1 signaling. We further review
      the importance of pyroptosis in vivo as a potent mechanism to clear intracellular
      pathogens.

PMID- 21884180
TI  - The machinery of Nod-like receptors: refining the paths to immunity and cell
      death.
AB  - One of the fundamental aspects of the innate immune system is its capacity to
      discriminate between self and non-self or altered self, and to quickly respond by
      eliciting effector mechanisms that act in concert to restore normalcy. This
      capacity is determined by a set of evolutionarily conserved pattern recognition
      receptors (PRRs) that sense the presence of microbial motifs or endogenous danger
      signals, including tissue damage, cellular transformation or metabolic
      perturbation, and orchestrate the nature, duration and intensity of the innate
      immune response. Nod-like receptors (NLRs), a group of intracellular PRRs, are
      particularly essential as evident by the high incidence of genetic variations in
      their genes in various diseases of homeostasis. Here, I overview the signaling
      mechanisms of NLRs and discuss the mounting evidence of evolutionary conservation
      between their pathways and the cell death machinery. I also describe their
      effector functions that link the sensing of danger to the induction of
      inflammation, autophagy or cell death.

PMID- 21884181
TI  - Monsters and dragons and sharks--oh my!

PMID- 21884179
TI  - Mitoxosome: a mitochondrial platform for cross-talk between cellular stress and
      antiviral signaling.
AB  - Evidence is accumulating that the mitochondria form an integral platform from
      which innate signaling takes place. Recent studies revealed that the mitochondria
      are shaping the innate response to intracellular pathogens, and mitochondrial
      function is modulating and being modulated by innate immune signaling. Further,
      cell biologic analyses have uncovered the dynamic relocalization of key
      components involved in cytosolic viral recognition and signaling to the
      mitochondria, as well as the mobilization of mitochondria to the sites of viral
      replication. In this review, we provide an integrated view of how cellular stress
      and signals following cytosolic viral recognition are intimately linked and
      coordinated at the mitochondria. We incorporate recent findings into our current
      understanding of the role of mitochondrial function in antiviral immunity and
      suggest the existence of a 'mitoxosome', a mitochondrial oxidative signalosome
      where multiple pathways of viral recognition and cellular stress converge on the
      surface of the mitochondria to facilitate a coordinated antiviral response.

PMID- 21884182
TI  - Unique urinalysis.

PMID- 21884183
TI  - The need for cytologic/histologic correlation studies to establish a cytologic
      grading system for canine mast cell tumors in veterinary medicine.

PMID- 21884184
TI  - Canine reference intervals for the Sysmex XT-2000iV hematology analyzer.
AB  - BACKGROUND: The laser-based Sysmex XT-2000iV hematology analyzer is increasingly
      used in veterinary clinical pathology laboratories, and instrument-specific
      reference intervals for dogs are not available. OBJECTIVE: The purpose of this
      study was to establish canine hematologic reference intervals according to
      International Federation of Clinical Chemistry and Clinical and Laboratory
      Standards Institute guidelines using the Sysmex XT-2000iV hematology analyzer.
      METHODS: Blood samples from 132 healthy purebred dogs from France, selected to
      represent the most prevalent canine breeds in France, were analyzed. Blood smears
      were scored for platelet (PLT) aggregates. Reference intervals were established
      using the nonparametric method. PLT and RBC counts obtained by impedance and
      optical methods were compared. Effects of sex and age on reference intervals were
      determined. RESULTS: The correlation between impedance (I) and optical (O)
      measurements of RBC and PLT counts was excellent (Pearson r=.99 and .98,
      respectively); however, there were significant differences between the 2 methods
      (Student's paired t-test, P<.0001). Differences between sexes were not
      significant except for HCT, PLT-I, and PLT-O. WBC, lymphocyte, and neutrophil
      counts decreased significantly with age (ANOVA, P<.05). Median eosinophil counts
      were higher in Brittany Spaniels (1.87 * 10(9) /L), Rottweilers (1.41 * 10(9)
      /L), and German Shepherd dogs (1.38 * 10(9) /L) than in the overall population
      (0.9 * 10(9) /L). PLT aggregates were responsible for lower PLT counts by the
      impedance, but not the optical, method. CONCLUSION: Reference intervals for
      hematologic analytes and indices were determined under controlled preanalytical
      and analytical conditions for a well-characterized population of dogs according
      to international recommendations.

PMID- 21884185
TI  - Canine differential leukocyte counting with the CellaVision DM96Vision, Sysmex XT
      2000iV, and Advia 2120 hematology analyzers and a manual method.
AB  - BACKGROUND: For differential leukocyte counts, automated blood smear evaluation
      systems have been too slow or inaccurate to replace or supplement the manual
      differential count. The CellaVision DM96Vision (DM96V), a new instrument, is an
      automated image analysis system that is rapid and accurate enough to be used for
      enumerating human leukocytes and may be useful for analysis of canine blood.
      OBJECTIVES: The aims of this study were to evaluate the performance of the DM96V
      in differential counting of canine leukocytes, to compare its performance with
      that of other methods, and to analyze interoperator variability. METHODS: Four
      methods of determining the leukocyte differential count of 108 canine blood
      samples were compared based on agreement, precision, and errors as well as
      relative performance. Differential counts were obtained using the DM96V, the
      manual method, and automated methods performed by the Advia 2120 and Sysmex XT
      2000iV. RESULTS: All leukocyte types were detected by the DM96V and the manual
      method, and all 4 methods had similar mean and median results in most cases. The
      automated methods were more precise than either the DM96V or manual method when
      comparing identification of a single type of leukocyte, especially neutrophils
      and lymphocytes. However, precision of the automated methods was only fair for
      monocytes, and the Advia and Sysmex failed to identify basophils. The Advia
      reported fewer monocytes and eosinophils than did the other methods.
      Significantly fewer lymphocytes were identified by the manual method than by the
      Sysmex, Advia, and DM96V. The DM96V occasionally presented duplicate images of
      the same neutrophils. CONCLUSIONS: The CellaVision DM96V is a satisfactory system
      for facilitating canine differential leukocyte counting. The DM96V differential
      count was more similar to the manual count than to automated counts, which were
      more precise but had errors and omissions in detecting some types of leukocytes.

PMID- 21884186
TI  - Hematologic and serum biochemical reference values for the wild Spectacled
      Caiman, Caiman crocodilus crocodilus, from the Venezuelan plains.
AB  - BACKGROUND: Commercial farming of Caiman crocodilus crocodilus has had an impact
      on the use of this species for meat consumption and the leather industry.
      Spectacled Caimans comprise part of the South American plains biodiversity.
      Misinterpretation of laboratory data is a risk owing to the limited hematologic
      and serum biochemical values available for this species. OBJECTIVE: The aim of
      this study was to determine hematologic and serum biochemical values for wild
      Spectacled Caimans from the Venezuelan plains. METHODS: Blood samples were
      collected form the caudal tail vein of 100 Spectacled Caimans (40 males and 60
      females) from the plains located in the State of Apure. Values for RBC count,
      PCV, hemoglobin concentration, WBC absolute and differential counts, and
      thrombocyte counts were obtained using manual methods, and RBC indices were
      calculated. Serum biochemical analysis included measurement of alkaline
      phosphatase, alanine aminotransferase, aspartate aminotransferase, and creatine
      kinase activities and concentrations of total protein and albumin. Comparisons
      between sexes were analyzed using the Mann-Whitney test. RESULTS: Reference
      values for wild Spectacled Caimans were determined. Minor differences in
      hematologic values, particularly for RBC counts, were found compared with
      previously published values for this species. Serum biochemical values were
      similar to those available for other crocodilians. There were no significant
      differences between males and females. CONCLUSIONS: Minor differences between the
      values obtained for wild Spectacled Caimans and those previously published for
      this species may be related to differences in methodology and environmental
      conditions. Availability of hematologic and serum biochemical reference values
      will be useful for accurate diagnosis and management of disease in this species.

PMID- 21884187
TI  - What is your diagnosis? Unilateral ovarian mass in a mare.

PMID- 21884188
TI  - What is your diagnosis? Unexpected finding in sedimented urine from a dog.

PMID- 21884190
TI  - What on earth?!: diatomaceous earth as evidence of delusional infestation.

PMID- 21884191
TI  - Provisioning.

PMID- 21884194
TI  - Statistics, probability, significance, likelihood: words mean what we define them
      to mean.

PMID- 21884195
TI  - Roger Cotton Histopathology Prize 2010.

PMID- 21884196
TI  - Loss of dystroglycan function in oesophageal cancer.
AB  - AIMS:  Oesophageal cancer is an increasingly common human malignancy, with its
      incidence in the West rapidly rising. It is associated with a very poor
      prognosis, and its exact pathogenesis is uncertain. Dystroglycan and E-cadherin
      are cell adhesion molecules, the loss of which is often related to tumour
      differentiation, aggressiveness and invasiveness. The aim was therefore to
      evaluate their roles in oesophageal carcinogenesis. METHODS AND RESULTS: mRNA and
      protein levels of dystroglycan and E-cadherin were examined in oesophageal normal
      and tumour tissue samples, and in FLO-1 oesophageal adenocarcinoma cells, using
      immunohistochemistry, western blotting and reverse transcription polymerase chain
      reaction. E-cadherin,alpha-dystroglycan and beta-dystroglycan levels were
      decreased in the oesophageal primary tumour samples, despite the presence of
      normal levels of dystroglycan mRNA. In FLO-1 cells, increasing cell density
      caused a decrease in protein levels of beta-dystroglycan over time, despite the
      persistent presence of dystroglycan mRNA. Re-expression of dystroglycan in FLO-1
      cells reduced the numbers and size of colonies formed in soft agar, indicative of
      a role for dystroglycan in suppressing the tumour phenotype. CONCLUSIONS: The
      adenocarcinoma cells mirrored the in vivo situation with respect to dystroglycan
      function, making this a useful model of oesophageal carcinogenesis; moreover,
      loss of dystroglycan protein, despite the presence of dystroglycan mRNA, points
      to a post-translational mechanism of dystroglycan loss.

PMID- 21884197
TI  - Comparison of gastro-oesophageal junction carcinomas in Chinese versus American
      patients.
AB  - AIMS: To compare the clinical and pathological features of gastro-oesophageal
      junction (GEJ) carcinomas in Chinese and American patients. METHODS AND RESULTS:
      Eighty consecutive patients with a GEJ carcinoma (43 from mainland China, and 37
      from the USA) were evaluated for association with Barrett oesophagus (BO),
      chronic Helicobacter pylori gastritis, intestinal metaplasia, and outcome. GEJ
      carcinomas were defined as tumours that were located within 20 mm of, and
      crossed, the GEJ. Overall, GEJ carcinomas from Chinese patients revealed
      significantly more frequent location in the proximal stomach, higher pathological
      stage, larger size, younger patient age, and association with chronic H. pylori
      gastritis. In contrast, GEJ cancers from American patients showed a strong
      association with distal oesophageal location, BO, and associated intestinal
      metaplasia and dysplasia. Pathologically, GEJ carcinomas from American patients
      were predominantly adenocarcinomas, whereas Chinese patients showed a higher
      proportion of mucinous, adenosquamous, acinar or neuroendocrine tumours. Overall,
      3- and 5-year survival rates were statistically similar between both patient
      groups, but upon multivariate analysis, Chinese patients showed statistically
      better survival rates for stage III tumours. CONCLUSIONS: Most GEJ carcinomas in
      patients from China represent proximal gastric cancers associated with chronic H.
      pylori gastritis, and BO-associated carcinomas are rare among this patient
      population.

PMID- 21884198
TI  - Phospholipase A2 group IIA expression correlates with prolonged survival in
      gastric cancer.
AB  - AIMS:   The secreted phospholipase A2 type IIA (PLA2G2A) gene has been identified
      as a modifier of intestinal adenoma multiplicity in Apc(Min/+) mice. The aim of
      the present study was to analyse the clinical significance of PLA2G2A expression
      in human gastric cancer. METHODS AND RESULTS:   Using immunohistochemistry,
      cytoplasmic immunoreactivity of PLA2G2A was observed in 27% (40 of 149) of
      gastric cancer tissues compared with negative staining in normal mucosa. The
      PLA2G2A expression rate in well-differentiated carcinoma was elevated
      significantly compared with that in poorly differentiated carcinoma (46% versus
      19%, P = 0.001). Statistical analysis also revealed that PLA2G2A expression
      correlated negatively with depth of mural invasion, lymph node metastasis and
      tumour-node-metastasis (TNM) stage (P < 0.05). Patients with positive PLA2G2A
      expression showed higher 5-year overall survival than those with negative
      expression (P = 0.0004). In intestinal metaplasia, PLA2G2A was found to be
      abundant in Paneth cells. The coexistence of PLA2G2A and lysozyme was observed in
      Paneth cell-rich gastric cancer (P < 0.0001). CONCLUSIONS:   PLA2G2A may predict
      survival and might be a potential biomarker for early detection and
      individualized therapy.

PMID- 21884199
TI  - Low expression of Granzyme B in colorectal cancer is associated with signs of
      early metastastic invasion.
AB  - AIMS: Tumour-infiltrating forkhead box P3 (FoxP3+ ) regulatory T cells (T(regs) )
      have stronger prognostic significance than cytotoxic CD8+ T cells in colorectal
      cancer (CRC). Because there is evidence that some tumour-infiltrating CD8+ T
      cells may be inactive, the present study aimed to investigate the prognostic
      significance of Granzyme B, one of the major effector molecules of T cells.
      METHODS AND RESULTS: A tissue microarray containing 963 CRCs was stained
      immunohistochemically for Granzyme B and the level of expression quantified by
      digital image analysis. Granzyme B expression was higher in tumours with
      microsatellite instability (P < 0.0001), a dense lymphocytic infiltrate (P <
      0.0001) and location in the proximal colon (P = 0.009), but lower in tumours with
      vascular invasion (P = 0.007), perineural invasion (P =0.041) and positive nodal
      status (P < 0.001). Elevated expression of Granzyme B was associated with
      improved survival on univariate analysis (hazard ratio = 0.65; 95% confidence
      interval 0.51-0.84; P = 0.001), but not in a multivariate model that included
      stage, vascular invasion and FoxP3+ T(reg) cell density. CONCLUSIONS: Low
      expression of Granzyme B was associated with early signs of metastasis in CRC.
      The stronger prognostic significance of FoxP3+ T(regs) is in keeping with animal
      models that suggest these cells act as gatekeepers for the release of Granzyme B
      from CD8+ T cells.

PMID- 21884200
TI  - Oestrogen receptor-beta CA repeat polymorphism is associated with incidence of
      colorectal cancer among females.
AB  - AIMS: Increasing evidence suggests an association between oestrogens and
      colorectal cancer. Oestrogen receptor beta, ER-beta, putatively plays a
      pathobiological role in colorectal cancer as colorectal epithelial cells
      frequently express ER-beta. The aim was to elucidate the association of the
      dinucleotide (CA) repeat polymorphism of the ER-beta gene (ESR2) with colorectal
      cancer. METHODS AND RESULTS:  Deoxyribonucleic acids extracted from the renal
      cortex of 1488 Japanese autopsies with complete clinical/pathological data were
      studied. CA repeat polymorphism was determined by polymerase chain reaction using
      fluorescein-labelled primers. Patients were divided into three genotype groups
      according to the number of CA repeats of each allele (S < 22, L >= 22); SS (with
      two S alleles), SL (with one each S and L allele) and LL (with two L alleles).
      The presence/absence of colorectal cancers was determined by examining the
      clinical records and autopsy material. The incidence of colorectal cancer was
      significantly different according to the ESR2 CA repeat genotype only among
      females (SS, 37/202 = 18.3%; SL, 19/332 = 5.7%; LL, 5/155 = 3.2%, P < 0.0001).
      Immunohistochemically, cancers in females with the SS genotype, but not the SL
      genotype, frequently expressed the C-terminus portion of ER-beta1 (wild-type ER
      beta). CONCLUSIONS: A role for ESR2 CA repeat polymorphism in the pathogenesis of
      colorectal cancer among females is suggested.

PMID- 21884201
TI  - Keratin 7 expression in colorectal cancer--freak of nature or significant
      finding?
AB  - AIMS:  To assess the prevalence of keratin 7 (K7) expression in colorectal cancer
      and to correlate findings with clinicopathological parameters and patients'
      outcome. METHOD AND RESULTS: A total of 370 patients were evaluated for K7
      expression by immunohistochemistry using a tissue microarray technique. K7
      expression was scored semiquantitatively as either focal (<10%), moderate (10
      50%) or extensive (>50%). In all, 32 (9%) tumours were immunoreactive for K7,
      with five cases showing extensive, four moderate and 23 focal expression,
      respectively. K7 expression was associated with poor tumour differentiation (P =
      0.005) and the extent of tumour budding (P = 0.02). In whole sections, K7
      immunoreactivity prevailed in single cells and small clusters of cells at the
      invasion front. Analysis of serial sections showed that K7-positive cells
      colocalized with keratin 20, whereas they lacked immunoreactivity for E-cadherin,
      MUC2 and MIB-1. Disease progression occurred in 52% of patients with K7-positive
      tumours and 41% with K7-negative tumours (P = 0.19); 48% of patients with K7
      positive tumours but only 33% with K7-negative tumours died of disease (P =
      0.06). CONCLUSIONS: Aberrant expression of K7 in budding cancer cells represents
      a modification of the epithelial phenotype ('epithelial-epithelial transition':
      EET) which may be linked to gains in motility and invasive potential.

PMID- 21884202
TI  - Prognostic value of ABCG2 in moderately and poorly differentiated intrahepatic
      cholangiocarcinoma.
AB  - AIMS:  Intrahepatic cholangiocarcinoma (ICC) is a primary hepatic malignancy
      derived from cholangiocytes. The survival rate of ICC patients is very low, and
      conventional chemotherapy is not effective in prolonging long-term survival.
      Adenosine 5'-triphosphate (ATP)-binding cassette (ABC) transporters mediate the
      transport of various substances in several cellular processes. The expression of
      ABCB1, ABCC1 and ABCG2 has been implicated in multidrug resistance and poor
      prognosis in several types of cancer. The aim of this study was to examine their
      expression in normal cholangiocytes and ICC tissues. METHODS AND RESULTS:  
      Immunohistochemistry was employed to evaluate the expression of these
      transporters in 60 cases of ICC with respect to clinicopathological features and
      patient outcome. The proportions of cases with loss of ABCB1, ABCC1 and ABCG2
      expression were 93.3%, 68.3% and 50%, respectively. Only the loss of ABCG2 was
      related to a worse prognosis (P = 0.031), and was associated with lymph node
      involvement (P = 0.003) and higher tumour grade (P = 0.028). Furthermore,
      multivariate analysis showed that the loss of ABCG2 expression was an independent
      prognostic factor in patients with moderately or poorly differentiated ICC (P =
      0.02). CONCLUSIONS: These results suggest that ABCG2 may be involved in
      cholangiocarcinogenesis; the loss of its expression may enhance tumour
      progression and contribute to aggressive growth of ICC.

PMID- 21884203
TI  - Increased alpha-B-crystallin expression in mammary metaplastic carcinomas.
AB  - AIMS:  Mammary metaplastic carcinoma is a rare breast carcinoma, and may present
      diagnostic difficulty. Alpha-B-crystallin has been recently reported to be
      expressed in basal-like and metaplastic carcinomas. METHODS AND RESULTS:  Thirty
      three metaplastic carcinomas, 44 conventional high-grade carcinomas and 28
      mesenchymal spindle cell neoplasms as controls were assessed for their expression
      of alphaB-crystallin and conventional basal-like phenotypic markers CK5/6, CK14,
      p63, c-kit and epidermal growth factor receptor (EGFR) by immunohistochemistry.
      Alpha-B-crystallin staining was positive in 68% of the metaplastic carcinomas
      with cytoplasmic staining in all tumour cell components. CK5/6, CK14, p63, c-kit
      and EGFR stained 43%, 68%, 45%, 21% and 25% of the metaplastic carcinomas,
      respectively. Combining these markers, 84% of the metaplastic carcinomas
      expressed either alphaB-crystallin or CK14. In comparison, only 14% (six cases)
      of conventional high-grade carcinoma and 7% (two cases) of mesenchymal spindle
      cell neoplasm expressed alphaB-crystallin; all but one of these carcinomas were
      ER/PR/HER2 triple-negative. CONCLUSIONS: Using alphaB-crystallin for diagnosis of
      metaplastic carcinoma gives a 68% sensitivity, 88% specificity, 74% positive
      predictive value, 85% negative predictive value and 78% accuracy. The sensitivity
      is enhanced to 84% with combinations of alphaB-crystallin/CK14. Alpha-B
      crystallin may be used as an adjunct marker in the diagnosis of metaplastic
      carcinoma.

PMID- 21884204
TI  - Angiopoietins 1 and 2 and Tie-2 receptor expression in human ductal breast
      disease.
AB  - AIMS:  This study aimed to identify the involvement of the angiopoietin/Tie-2
      receptor system in breast cancer development, progression, metastasis and
      angiogenesis. METHODS AND RESULTS: We quantified and correlated angiopoietin-1
      (Ang-1), Ang-2 and Tie-2 expression in sections of normal human breast, benign
      and premalignant hyperplastic tissue, pre-invasive and invasive cancer, and
      compared these findings with our previously published data on vascular
      endothelial growth factor (VEGF) and microvessel density (MVD) in the same
      samples. A breast cancer tissue microarray was used to evaluate the prognostic
      value of these factors. Histological analysis revealed a significant decrease in
      Ang-1 expression (P = 0.001) and an inverse correlation with MVD (r = -0.442, P =
      0.008) and VEGF (r = -0.510, P = 0.002) in the non-invasive lesions. In contrast
      Ang-2 expression increased significantly (P = 0.0004) with increasing severity of
      lesion and correlated with MVD (r = 0.570; P = 0.0002), while Tie-2 expression
      remained relatively unchanged. Expression of all three factors was reduced in
      invasive breast cancer and did not correlate with oestrogen receptor (ER),
      progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2),
      lymph node status or tumour grade. CONCLUSIONS: These data suggest that a change
      in the angiopoietin balance in favour of Ang-2 is associated with the angiogenic
      switch at the onset of hyperplasia in the breast. However, angiopoietins and the
      Tie-2 receptor are not related to known prognostic indicators in invasive breast
      cancer.

PMID- 21884205
TI  - Epidermal growth factor receptor gene amplification and protein overexpression in
      basal-like carcinoma of the breast.
AB  - AIMS: Epidermal growth factor receptor (EGFR) is frequently expressed in basal
      like breast cancer (BLBC). The aim of this study was to evaluate their
      correlation as detected by immunohistochemistry (IHC) or fluorescence in-situ
      hybridization (FISH). METHODS AND RESULTS: IHC for oestrogen receptor (ER),
      progesterone receptor (PR), human epidermal growth factor receptor (HER) 2,
      cytokeratin (CK) 5/6 and EGFR, and FISH for EGFR amplification, were performed in
      59 cases of BLBC. EGFR IHC results were scored semiquantitatively, and compared
      with its gene amplification status. ER, PR and HER2 were negative in all cases,
      whereas 35 and 55 cases were positive for CK5/6 and EGFR. For EGFR IHC, 20, 11,
      11 and 17 cases showed a negative, a low, an intermediate or a high staining
      level, respectively, and seven cases showed gene amplification by FISH, with two,
      19, 11 and 20 cases showing balanced monosony, disomy, trisomy, and polysomy
      respectively. Immunohistochemical expression in gene-amplified tumours was
      significantly higher than in those without amplification, including balanced
      polysomy tumours. EGFR immunohistochemical expression also correlated with the
      EGFR/chromosome 7 ratio. High sensitivity (86%) and negative predictive value
      (98%) were achieved with high-level immunohistochemical expression as a cut-off
      to predict gene amplification. CONCLUSIONS: High-level EGFR immunohistochemical
      expression correlated with and predicted EGFR amplification, and may be used as a
      screening method to exclude gene amplification.

PMID- 21884206
TI  - Expression of class 3 semaphorins and their receptors in human breast neoplasia.
AB  - AIMS: This study aimed to identify the involvement of class 3 semaphorins (Sema3)
      and receptors, neuropilins (Np1 and Np2) and plexins (A1-A4) in breast cancer
      development and angiogenesis. METHODS AND RESULTS: We quantified and correlated
      Sema3A, Sema3B, Sema3F and their known receptors and coreceptors Plexin-A1,
      Plexin-A3, Np1 and Np2 in sections of normal human breast, benign and pre
      malignant hyperplastic tissue, pre-invasive and invasive cancer, and compared
      these findings with our previously published data on vascular endothelial growth
      factor (VEGF) and microvessel density (MVD) in the same samples. Histological
      analysis revealed that Sema3B was expressed more strongly and widely than Sema3A
      and 3F in normal breast tissue and all three semaphorins decreased with the
      transition from in situ to invasive cancer (P < 0.014). Plexin-A3 decreased
      significantly with progression towards invasive cancer (P < 0.045), whereas
      Plexin-A1 expression was only significantly reduced once invasion had occurred (P
      = 0.012). Np1 and Np2 were expressed in both endothelial and epithelial/tumour
      cells. Np2 expression did not change, but Np1 expression significantly increased
      in the spectrum from hyperplasia to ductal carcinoma in situ (P < 0.035), but
      decreased with invasive cancer. CONCLUSION:  These data suggest that a decrease
      in class 3 semaphorin and their plexin receptors have some relationship with
      disease progression in ductal breast carcinoma.

PMID- 21884207
TI  - Nuclear translocation of beta-catenin synchronized with loss of E-cadherin in
      oral epithelial dysplasia with a characteristic two-phase appearance.
AB  - AIMS: One of the important histopathological characteristics of oral epithelial
      dysplasia is a two-phase appearance of rete processes, comprising an upper layer
      of keratinized cells and a lower layer of basaloid cells, and thereby creating a
      sharp contrast between these two separate cell populations. The aim of this study
      was to determine the cellular adhesion status of the basaloid cells. METHODS AND
      RESULTS: Immunohistochemistry for beta-catenin, E-cadherin and their related
      molecules was carried out in surgical specimens of two-phase epithelial dysplasia
      of the oral mucosa. The lower-half basaloid cells and the upper keratinized cells
      were microdissected separately, and extracted DNA samples were subjected to
      methylation-specific polymerase chain reaction amplification for E-cadherin. beta
      Catenin was immunolocalized within the nuclei and cytoplasm of Ki67-positive
      lower-half basaloid cells, as well as on the cell membrane of upper parakeratotic
      cells. The basaloid cells of the lower-half were also positive for matrix
      metalloproteinase-7 and cyclin D1, beta-catenin target gene products, alpha
      dystroglycan, tenascin-C, and perlecan, but not for E-cadherin. The promoter
      region of the E-cadherin gene was hypermethylated. CONCLUSIONS: The solid
      proliferation of lower-half E-cadherin-free basaloid cells is enhanced by Wnt
      signalling cascades, as well as by the intraepithelial extracellular matrix or
      its bound growth factors.

PMID- 21884208
TI  - Malignant potential of oral and labial chronic discoid lupus erythematosus: a
      clinicopathological study of 87 cases.
AB  - AIMS:  To investigate clinicopathological features and identify
      clinicopathological risk factors for the malignant transformation of oral and
      labial chronic discoid lupus erythematosus (DLE) in a relatively large number of
      patients from China. METHODS AND RESULTS: A total of 87 patients with clinical
      and histopathological diagnosis of DLE between 1993 and 2009 were reviewed
      retrospectively in our hospital. The average age at diagnosis was 51.7 years,
      with a male:female ratio of 1:1.8. The lower lip was the most common site
      (71.3%). We documented six DLE patients with malignant transformation. On
      univariate analysis, patients with high-risk dysplasia (P = 0.002) or aged >60 (P
      = 0.045) were associated with DLE malignant transformation, but gender, lesion
      site, smoking and alcohol intake were not risk factors. On multivariate analysis,
      high-risk dysplasia was a significant indicator for DLE malignant transformation.
      High-risk dysplasia was associated with a 14.24-fold [95% confidence interval
      (95% CI), 1.97-102.88; P = 0.008] increased risk of malignant transformation,
      compared with non/low-risk dysplasia. CONCLUSIONS: The utilization of high-risk
      dysplasia as a significant indicator for evaluating malignant transformation risk
      in patients with DLE is suggested, which may be helpful to guide treatment
      selection.

PMID- 21884210
TI  - CD34 and microtubule-associated protein 2 expression in dysembryoplastic
      neuroepithelial tumours with an emphasis on dual expression in non-specific
      types.
AB  - AIMS:  Three histological variants of dysembryoplastic neuroepithelial tumour
      (DNT) have been described, namely, simple, complex and non-specific. However, the
      concept of non-specific variants of DNT remains controversial, because they
      cannot be accurately distinguished by histological findings alone from ordinary
      gliomas. The aim was to characterize further the non-specific histological forms
      of DNT. METHODS AND RESULTS: Forty-one DNTs classified as three histological
      forms were investigated with CD34 and microtubule-associated protein 2 (MAP2)
      immunohistochemistry. CD34 immunoreactivity was more frequently observed in non
      specific DNT types (16/18 cases; 88.9%) than in classic types (6/23 cases; 26.1%)
      (P < 0.001). Peritumoral CD34 expression of non-neoplastic cells was
      significantly associated with CD34-positive tumours (20/22 cases; 90.9%) than
      with CD34-negative tumours (3/19 cases; 15.8%) (P < 0.001). MAP2 positivity in
      oligodendroglia-like cells or glial elements was significantly different between
      classic types and non-specific types (P = 0.025). CD34 and MAP2
      immunoreactivities were significantly more frequent in non-specific types (83.3%)
      than in simple (10%) and complex forms (30.8%) (P < 0.001). CONCLUSIONS: Non
      specific DNTs are glioneuronal tumours that have a heterogeneous population of
      cells with more immature neuronal and glial phenotypes. Furthermore, with regard
      to practical implications, combined analysis of CD34 and MAP2 is useful in
      distinguishing DNTs from particularly diagnostically challenging mimics.

PMID- 21884209
TI  - Glycoconjugate expression in adenoid cystic carcinoma of the salivary glands: up
      regulation of L1 predicts fatal prognosis.
AB  - AIMS:  The up-regulation of the cell adhesion molecule L1 has been associated
      with impaired prognosis in several cancers. This study aimed to identify
      potential prognostic markers, including L1, in adenoid cystic carcinoma of the
      salivary glands (ACCs), which might give additional insight into the molecular
      mechanisms underlying malignant progression. METHODS AND RESULTS: The expression
      of L1 was analysed in 34 primary ACCs (nine tubular, 15 cribriform, nine solid,
      one mixed) and correlated with recurrence, metastasis, overall survival and
      clinicopathological parameters. Independent of the histological subtype, intense
      L1 expression in the primary tumours was associated significantly with metastasis
      (P = 0.02) and death (P = 0.044). In the subgroup of cribriform ACCs, 10 of 15
      tumours contained pseudocysts, which were associated with significantly lower
      recurrence rates (P = 0.003), lower metastasis rates (P = 0.009) and a prolonged
      overall survival (P =0.004). CONCLUSIONS: Determination of L1 expression in
      primary ACCs improves risk estimations. As up-regulation of L1 expression
      predicts fatal prognosis, L1 might be involved functionally in growth and spread
      of ACC and might thus present a molecular target for future therapeutic
      strategies.

PMID- 21884211
TI  - No non-sentinel node involvement in melanoma patients with limited Breslow
      thickness and low sentinel node tumour load.
AB  - AIMS:  Most melanoma patients with a positive sentinel node (SN) undergo
      completion lymph node dissection and frequently experience associated morbidity.
      However, only 10-30% of SN-positive patients have further lymph node metastases.
      The aim of the present study was to predict the absence of non-SN metastases in a
      multicentre study of patients with a positive SN based on primary melanoma
      features and SN tumour load. METHODS AND RESULTS: Of 70 SN positive patients, 18
      had non-SN metastases. Penetrative depth of metastatic cells into the SN and SN
      tumour load was assessed by morphometry. None of the 14 patients (20%) with a
      Breslow thickness <2.0 mm and an SN tumour load <0.2 mm2 had non-SN metastases.
      Similarly, none of the 15 patients (21%) with a Breslow thickness <2.0 mm and SN
      penetrative depth <600 MUm had non-SN metastases. Lastly, none of the 14 patients
      (20%) with a Breslow thickness <2.0 mm and a diameter of the largest SN deposit
      <500 MUm had non-SN metastases. CONCLUSIONS: A combination of limited Breslow
      thickness and low SN tumour load predicts absence of non-SN metastases in
      melanoma patients with a positive SN with high accuracy. We propose that this
      subgroup may be spared completion lymph node dissection.

PMID- 21884212
TI  - Injection site pseudosarcoma in piriformis syndrome.
AB  - AIMS: Pseudosarcomatous reactive myofibroblastic proliferations have been
      described following surgery or trauma at a variety of anatomical sites. These
      types of reactions have not been previously described at injection sites. Here we
      evaluated prevalence, morphologic patterns and clinical resolution of such
      lesions. METHODS AND RESULTS: We analyzed 266 surgical resection specimens
      obtained during the definitive treatment of piriformis syndrome. Three cases
      showed exuberant reactive fibroblastic/myofibroblastic intramuscular
      proliferations, mimicking a sarcoma. In all three cases the surgeries were found
      to be preceded by local injections of cortisone and bupivacaine. Clinical follow
      up revealed no uncontrolled growth. CONCLUSIONS: As the clinical history of
      injections is often not provided, it is important to be aware of this pitfall
      when reviewing skeletal muscle resections for entrapment syndromes.

PMID- 21884213
TI  - Observer prediction of HER2 amplification in HercepTest 2+ breast cancers as a
      potential audit instrument.
AB  - AIMS: Correct assignment of human epidermal growth factor receptor 2 (HER2)
      status in breast cancer is important. Indeterminate (2+) HER2
      immunohistochemistry (IHC) is usually resolved by FISH for HER2 gene
      amplification. It was hypothesised that predicting HER2 amplification in IHC 2+
      cases could improve audit of HER2 IHC and its interpretation. METHODS AND
      RESULTS: One observer (J. J. G.) interpreted 4343 assessable HercepTests on
      consecutive breast cancers from the West of Scotland over 45 consecutive months
      during 2007-2010, with 2+ cases classified prospectively as 'probably amplified',
      'possibly amplified' or 'probably not amplified' prior to FISH. A HER2 to
      chromosome 17 FISH ratio >2 was taken to define HER2 amplification. There were
      265 3+ cases (6.1%) and 883 2+ cases (20.3%). Of 187 'probably amplified' 2+
      cases, 166 (88.8%) were amplified, as were 90 (37.8%) of 238 'possibly amplified'
      2+ cases. Of 458 'probably not amplified' but still 2+ cases, 59 (12.8%) were in
      fact amplified (overall chi2 333.89, df 2, P < 0.0001). In total, 580 of 4343
      (13.4%) cancers were HER2-positive (265 3+ by IHC and 315 2+ and HER2 amplified).
      CONCLUSIONS: Breast cancers HER2-indeterminate (2+) by HercepTest IHC can be
      strongly separated into those probably HER2 amplified, a core indeterminate group
      and those probably not HER2 amplified. The percentage of HER2 amplified cases in
      each category is proposed as an instrument for comparison of HER2 IHC and its
      interpretation between laboratories and observers.

PMID- 21884214
TI  - 'Difficult to diagnose' desmoid tumours: a potential role for CTNNB1 mutational
      analysis.
AB  - AIMS: The utility of CTNNB1 (encoding beta-catenin) genotyping for diagnosing
      sporadic desmoid tumours (DT) when traditional clinicopathological parameters
      were inconclusive was evaluated. METHODS AND RESULTS: Cases included were: (i)
      new primary lesions where initial DT diagnosis was inconclusive; and (ii)
      possible recurrent DT versus scar. Formalin-fixed paraffin-embedded (FFPE)
      tissues were obtained via needle biopsy or a surgical excision (57 specimens) as
      part of initial assessment. DNA extraction, CTNNB1 exon 3 amplification and
      sequencing were conducted in a Clinical Laboratory Improvement Amendments of 1988
      (CLIA)-approved molecular diagnostics laboratory. For patients with no previous
      DT history (n = 47) sequencing identified mutations in 30 (64%), substantiating
      DT diagnosis. In biopsies with non-mutated (NM) CTNNB1 (n = 17) the test was
      inconclusive; in seven of these, a diagnosis of DT was strongly favoured in the
      subsequent surgical resection specimen. Ten patients with previously resected DT
      were evaluated; mutation was identified in six cases (60%), indicating DT over
      scar. In two (20%) with primary tumours harbouring CTNNB1 mutation no mutation
      was found, favouring scar over DT; the other two NM-CTNNB1 cases (20%) were
      inconclusive. CONCLUSIONS: CTNNB1 genotyping can be very useful in 'difficult to
      diagnose' lesions when the differential diagnosis includes DT. Recognizing
      inherent test limitations, the presence of CTNNB1 mutation can inform the
      therapeutic approach.

PMID- 21884215
TI  - BackgroundCorrector--a software program for fast and user-friendly improvement of
      digital photomicrographs.

PMID- 21884216
TI  - Multiple intratumoral KRAS mutations can clonally segregate to different lymph
      node metastases in colon cancer.

PMID- 21884217
TI  - Reduced numbers of regulatory T cells in breast carcinoma with medullary
      features.

PMID- 21884218
TI  - Epstein-Barr virus in the germinal centres of adenopathies affected by classic
      Hodgkin lymphoma.

PMID- 21884219
TI  - Synchronous Epstein-Barr virus-positive diffuse large B-cell lymphoma of the
      elderly and Epstein-Barr virus-positive classical Hodgkin lymphoma.

PMID- 21884220
TI  - Solitary bronchial neuroma associated with asthma: chronic irritation
      pathogenesis?

PMID- 21884221
TI  - Cross-cultural similarities and differences in person-body reasoning:
      experimental evidence from the United Kingdom and Brazilian Amazon.
AB  - We report the results of a cross-cultural investigation of person-body reasoning
      in the United Kingdom and northern Brazilian Amazon (Marajo Island). The study
      provides evidence that directly bears upon divergent theoretical claims in
      cognitive psychology and anthropology, respectively, on the cognitive origins and
      cross-cultural incidence of mind-body dualism. In a novel reasoning task, we
      found that participants across the two sample populations parsed a wide range of
      capacities similarly in terms of the capacities' perceived anchoring to bodily
      function. Patterns of reasoning concerning the respective roles of physical and
      biological properties in sustaining various capacities did vary between sample
      populations, however. Further, the data challenge prior ad-hoc categorizations in
      the empirical literature on the developmental origins of and cognitive
      constraints on psycho-physical reasoning (e.g., in afterlife concepts). We
      suggest cross-culturally validated categories of "Body Dependent" and "Body
      Independent" items for future developmental and cross-cultural research in this
      emerging area.

PMID- 21884222
TI  - How linguistic and cultural forces shape conceptions of time: English and
      Mandarin time in 3D.
AB  - In this paper we examine how English and Mandarin speakers think about time, and
      we test how the patterns of thinking in the two groups relate to patterns in
      linguistic and cultural experience. In Mandarin, vertical spatial metaphors are
      used more frequently to talk about time than they are in English; English relies
      primarily on horizontal terms. We present results from two tasks comparing
      English and Mandarin speakers' temporal reasoning. The tasks measure how people
      spatialize time in three-dimensional space, including the sagittal (front/back),
      transverse (left/right), and vertical (up/down) axes. Results of Experiment 1
      show that people automatically create spatial representations in the course of
      temporal reasoning, and these implicit spatializations differ in accordance with
      patterns in language, even in a non-linguistic task. Both groups showed evidence
      of a left-to-right representation of time, in accordance with writing direction,
      but only Mandarin speakers showed a vertical top-to-bottom pattern for time
      (congruent with vertical spatiotemporal metaphors in Mandarin). Results of
      Experiment 2 confirm and extend these findings, showing that bilinguals'
      representations of time depend on both long-term and proximal aspects of language
      experience. Participants who were more proficient in Mandarin were more likely to
      arrange time vertically (an effect of previous language experience). Further,
      bilinguals were more likely to arrange time vertically when they were tested in
      Mandarin than when they were tested in English (an effect of immediate linguistic
      context).

PMID- 21884223
TI  - Case of malignant melanoma associated with a sarcoid reaction.

PMID- 21884224
TI  - Parent-of-origin effect: a hint from vitiligo epidemiology.

PMID- 21884225
TI  - "Gentle cesareans": better in some respects, but fewer cesareans are better
      still.

PMID- 21884226
TI  - United States home births increase 20 percent from 2004 to 2008.
AB  - BACKGROUND: After a gradual decline from 1990 to 2004, the percentage of births
      occurring at home increased from 2004 to 2008 in the United States. The objective
      of this report was to examine the recent increase in home births and the factors
      associated with this increase from 2004 to 2008. METHODS: United States birth
      certificate data on home births were analyzed by maternal demographic and medical
      characteristics. RESULTS: In 2008, there were 28,357 home births in the United
      States. From 2004 to 2008, the percentage of births occurring at home increased
      by 20 percent from 0.56 percent to 0.67 percent of United States births. This
      rise was largely driven by a 28 percent increase in the percentage of home births
      for non-Hispanic white women, for whom more than 1 percent of births occur at
      home. At the same time, the risk profile for home births has been lowered, with
      substantial drops in the percentage of home births of infants who are born
      preterm or at low birthweight, and declines in the percentage of home births that
      occur to teen and unmarried mothers. Twenty-seven states had statistically
      significant increases in the percentage of home births from 2004 to 2008; only
      four states had declines. CONCLUSION: The 20 percent increase in United States
      home births from 2004 to 2008 is a notable development that will be of interest
      to practitioners and policymakers. (BIRTH 38:3 September 2011).

PMID- 21884227
TI  - Mothers' level of education and childbirth interventions: A population-based
      study in Flanders, Northern Belgium.
AB  - BACKGROUND:   Interventions to influence the time and way to be born have been a
      global concern for decades. Yet, limited information is available on what drives
      these interventions and their variation in frequency among countries,
      institutions, and practitioners. The objective of this study was to examine to
      what extent first-time mothers' educational achievement contributes to the
      frequency of childbirth interventions. METHODS:   Childbirth interventions,
      including induction of labor, cesarean section, instrumental delivery, and
      epidural analgesia, registered by the Flemish Study Center for Perinatal
      Epidemiology for Belgian-born nulliparous women from 1999 to 2006, were linked to
      the level of maternal education, recorded by the Belgian civil birth
      registration. Education was divided into four levels based on the highest diploma
      attained and adjusted for marital and occupational status. RESULTS:   Frequencies
      of all interventions were inversely related to the level of maternal education.
      The effect remained after adjustment for birth year, maternal age, marital
      status, occupation, infant birthweight, gestational age, assisted conception, and
      type of hospital. Effect sizes between highest and lowest levels of education
      were relatively small for operative (31% vs 36%) and instrumental vaginal birth
      (20.7% vs 22.3%) compared with "initiated delivery" (defined as labor induction
      and prelabor cesarean section; 30.2% vs 40.3%) and epidural analgesia (66.8% vs
      78.0%). The educational gradient in initiated delivery occurred at all
      gestational ages, contributing to lower gestational age and lower birthweight of
      term infants with decreasing levels of education. CONCLUSIONS:   In an affluent
      society with universal and equitable access to maternity care, the more educated
      women are, the more likely they are to have a spontaneous labor and spontaneous
      birth without intervention. (BIRTH 38:3 September 2011).

PMID- 21884228
TI  - The use of complementary and alternative medicine during pregnancy: a
      longitudinal study of Australian women.
AB  - BACKGROUND: The use of complementary and alternative medicine is increasingly
      prevalent in contemporary Western societies. The objective of this study was to
      explore trends and patterns in complementary and alternative medicine
      practitioner consultations and the use of complementary and alternative medicine
      consumption before, during, and after pregnancy and between pregnancies. METHODS:
      Analysis focused on data from 13,961 women from the younger cohort of the
      Australian Longitudinal Study on Women's Health collected between 1996 and 2006.
      Chi-square tests were employed for the cross-sectional analysis of categorical
      variables and t tests for continuous variables. Generalized estimating equations
      were used to conduct multivariate longitudinal analysis. RESULTS: Complementary
      and alternative medicine use among pregnant and nonpregnant women continued to
      increase over the 10-year period. Although pregnancy status was not predictive of
      the use of alternative treatments, pregnant women employed these therapies or
      modalities for the relief of pregnancy-related complaints and symptoms. Analysis
      also revealed that women used complementary and alternative treatments
      selectively during pregnancy. CONCLUSIONS: This study highlights the need for
      further research that is sensitive to the consumption of specific complementary
      and alternative therapies or modalities and to the wider contexts within which
      women perceive risk associated with their use of complementary and alternative
      treatments.

PMID- 21884229
TI  - The experience of pregnancy and birth with midwives: results from the Canadian
      maternity experiences survey.
AB  - BACKGROUND: In Canada maternity care is publicly funded, and although women may
      choose their care providers, choices may be limited. The purpose of this study
      was to compare perceptions of maternity outcomes and experiences of those who
      received care from midwives with those who received care from other providers.
      METHODS: Based on the 2006 Canadian census, a random sample of women (n = 6,421)
      who had recently given birth in Canada completed a computer-assisted telephone
      interview for the Maternity Experiences Survey. The sample was stratified
      according to province or territory where birth occurred, age, rural or urban
      residence, and presence of other children in the home. Those who were 15 years of
      age and older, gave birth to a singleton baby, and were living with their infant
      were eligible for inclusion. RESULTS: Women whose primary prenatal providers were
      midwives had fewer ultrasounds and were more likely to attend prenatal classes
      and have at least five or more prenatal visits. They were also more likely to
      rate satisfaction with their maternity experience as "very positive" and be
      satisfied with information provided on a variety of pregnancy and birth topics if
      their primary prenatal provider was a midwife. They were almost half as likely to
      experience induction and 7.33 times more likely to experience a medication-free
      delivery. They were more likely to initiate and maintain breastfeeding at 3 and 6
      months. CONCLUSIONS: Evidence shows that midwifery outcomes and levels of
      satisfaction meet or exceed Canadian maternity care standards. Facilitation of
      the continuing integration of midwives as autonomous practitioners throughout
      Canada is recommended. (BIRTH 38:3 September 2011).

PMID- 21884230
TI  - Posttraumatic stress disorder in new mothers: results from a two-stage U.S.
      national survey.
AB  - BACKGROUND: Prevalence rates of women in community samples who screened positive
      for meeting the DSM-IV criteria for posttraumatic stress disorder after
      childbirth range from 1.7 to 9 percent. A positive screen indicates a high
      likelihood of this postpartum anxiety disorder. The objective of this analysis
      was to examine the results that focus on the posttraumatic stress disorder data
      obtained from a two-stage United States national survey conducted by Childbirth
      Connection: Listening to Mothers II (LTM II) and Listening to Mothers II
      Postpartum Survey (LTM II/PP). METHODS: In the LTM II study, 1,373 women
      completed the survey online, and 200 mothers were interviewed by telephone. The
      same mothers were recontacted and asked to complete a second questionnaire 6
      months later and of those, 859 women completed the online survey and 44 a
      telephone interview. Data obtained from three instruments are reported in this
      article: Posttraumatic Stress Disorder Symptom Scale-Self Report (PSS-SR),
      Postpartum Depression Screening Scale (PDSS), and the Patient Health
      Questionnaire-2 (PHQ-2). RESULTS: Nine percent of the sample screened positive
      for meeting the diagnostic criteria of posttraumatic stress disorder after
      childbirth as determined by responses on the PSS-SR. A total of 18 percent of
      women scored above the cutoff score on the PSS-SR, which indicated that they were
      experiencing elevated levels of posttraumatic stress symptoms. The following
      variables were significantly related to elevated posttraumatic stress symptoms
      levels: low partner support, elevated postpartum depressive symptoms, more
      physical problems since birth, and less health-promoting behaviors. In addition,
      eight variables significantly differentiated women who had elevated posttraumatic
      stress symptom levels from those who did not: no private health insurance,
      unplanned pregnancy, pressure to have an induction and epidural analgesia,
      planned cesarean birth, not breastfeeding as long as wanted, not exclusively
      breastfeeding at 1 month, and consulting with a clinician about mental well-being
      since birth. A stepwise multiple regression revealed that two predictor variables
      significantly explained 55 percent of the variance in posttraumatic stress
      symptom scores: depressive symptom scores on the PHQ-2 and total number of
      physical symptoms women were experiencing at the time they completed the LTM
      II/PP survey. CONCLUSION: In this two-stage national survey the high percentage
      of mothers who screened positive for meeting all the DSM-IV criteria for a
      posttraumatic stress disorder diagnosis is a sobering statistic.

PMID- 21884231
TI  - Breastfeeding policies and practices in Canadian hospitals: comparing 1993 with
      2007.
AB  - BACKGROUND: The Baby-Friendly Hospital Initiative (BFHI) promotes the World
      Health Organization International Code of Marketing of Breast-milk Substitutes
      (WHO Code) and the WHO/UNICEF's Ten Steps to Successful Breastfeeding (Ten
      Steps). The purpose of this study is to describe and compare maternity hospitals'
      adherence to the BFHI in 1993 and 2007 for Canada and for each province and
      territory. METHODS: A survey of all Canadian maternity hospitals was conducted in
      1993 and 2007 on routine maternity care practices and policies including infant
      feeding. RESULTS: The overall response rate was 91 percent (n = 523/572
      hospitals) in 1993 and 92 percent (n = 323/353 hospitals) in 2007. Eighty-two
      percent (415/507) of hospitals in 1993 and 68 percent (198/292) in 2007 had
      exclusive contracts with formula companies. Fifty-eight percent (302/517) of
      hospitals in 1993 and 90 percent (289/322) in 2007 never gave breastfeeding
      mothers sample packs containing formula. Fifty-eight percent (296/507) in 1993
      and 85 percent (273/321) in 2007 had written breastfeeding policies (Step 1); 97
      percent (503/518) in 1993 and 99 percent (320/322) in 2007 allowed mothers to
      breastfeed, on cue, whenever the babies indicated an interest 24 hours a day
      (Step 8); 24 percent (126/519) in 1993 and 64 percent (206/321) in 2007 reported
      that they did not provide soothers (Step 9); 58 percent (297/513) in 1993 and 68
      percent (215/316) in 2007 always offered information on breastfeeding support
      groups and/or advice at time of discharge (Step 10). CONCLUSIONS: In the 14 years
      separating the two surveys, Canadian maternity hospitals substantially improved
      their implementation of the WHO Code and their adherence to the WHO/UNICEF Ten
      Steps.

PMID- 21884232
TI  - Impact of baby-friendly hospital practices on breastfeeding in Hong Kong.
AB  - BACKGROUND: The World Health Organization (WHO) developed the Baby-Friendly
      Hospital Initiative to improve hospital maternity care practices that support
      breastfeeding. In Hong Kong, although no hospitals have yet received the Baby
      Friendly status, efforts have been made to improve breastfeeding support. The aim
      of this study was to examine the impact of Baby-Friendly hospital practices on
      breastfeeding duration. METHODS: A sample of 1,242 breastfeeding mother-infant
      pairs was recruited from four public hospitals in Hong Kong and followed up
      prospectively for up to 12 months. The primary outcome variable was defined as
      breastfeeding for 8 weeks or less. Predictor variables included six Baby-Friendly
      practices: breastfeeding initiation within 1 hour of birth, exclusive
      breastfeeding while in hospital, rooming-in, breastfeeding on demand, no
      pacifiers or artificial nipples, and information on breastfeeding support groups
      provided on discharge. RESULTS: Only 46.6 percent of women breastfed for more
      than 8 weeks, and only 4.8 percent of mothers experienced all six Baby-Friendly
      practices. After controlling for all other Baby-Friendly practices and possible
      confounding variables, exclusive breastfeeding while in hospital was protective
      against early breastfeeding cessation (OR: 0.61; 95% CI: 0.42-0.88). Compared
      with mothers who experienced all six Baby-Friendly practices, those who
      experienced one or fewer Baby-Friendly practices were almost three times more
      likely to discontinue breastfeeding (OR: 3.13; 95% CI: 1.41-6.95). CONCLUSIONS:
      Greater exposure to Baby-Friendly practices would substantially increase new
      mothers' chances of breastfeeding beyond 8 weeks postpartum. To further improve
      maternity care practices in hospitals, institutional and administrative support
      are required to ensure all mothers receive adequate breastfeeding support in
      accordance with WHO guidelines.

PMID- 21884233
TI  - Poor health-related quality of life after severe preeclampsia.
AB  - BACKGROUND: Preeclampsia is a major complication of pregnancy associated with
      increased maternal morbidity and mortality, and adverse birth outcomes. The
      objective of this study was to describe changes in all domains of health-related
      quality of life between 6 and 12 weeks postpartum after mild and severe
      preeclampsia; to assess the extent to which it differs after mild and severe
      preeclampsia; and to assess which factors contribute to such differences.
      METHODS: We conducted a prospective multicenter cohort study of 174 postpartum
      women who experienced preeclampsia, and who gave birth between February 2007 and
      June 2009. Health-related quality of life was measured at 6 and 12 weeks
      postpartum by the RAND 36-item Short-Form Health Survey (SF-36). The population
      for analysis comprised women (74%) who obtained scores on the questionnaire at
      both time points. RESULTS:   Women who experienced severe preeclampsia had a
      lower postpartum health-related quality of life than those who had mild
      preeclampsia (all p < 0.05 at 6 wk postpartum). Quality of life improved on
      almost all SF-36 scales from 6 to 12 weeks postpartum (p < 0.05). Compared with
      women who had mild preeclampsia, those who experienced severe preeclampsia had a
      poorer mental quality of life at 12 weeks postpartum (p < 0.05). Neonatal
      intensive care unit admission and perinatal death were contributing factors to
      this poorer mental quality of life. CONCLUSIONS: Obstetric caregivers should be
      aware of poor health-related quality of life, particularly mental health quality
      of life in women who have experienced severe preeclampsia (especially those
      confronted with perinatal death or their child's admission to a neonatal
      intensive care unit), and should consider referral for postpartum psychological
      care.

PMID- 21884234
TI  - Affirming motherhood: validation and invalidation in women's perinatal hospice
      narratives.
AB  - BACKGROUND: Perinatal hospice is an option for women who learn during pregnancy
      that their fetuses are affected by terminal conditions and choose to continue
      their affected pregnancies. These women face emotional pain and the impending
      loss of their fetuses or infants. The aims of this study were to explore the
      experiences of perinatal hospice mothers, to gather knowledge useful to health
      professionals, and to guide future research. METHODS:   Narrative analysis was
      performed using the personal stories of 15 women who continued pregnancies
      affected by lethal fetal anomalies. RESULTS: The participants identified
      themselves as mothers and their fetuses or newborns as babies. Mothers valued
      caring for and interacting with their babies. Health professionals who affirmed
      their status as mothers, the value of their babies, and the significance of their
      losses were perceived as supportive. Invalidating attitudes and behavior caused
      significant distress among mothers. CONCLUSIONS: Optimal care of perinatal
      hospice mothers supports the development of maternal identity and contact between
      mothers and newborns when desired. Professionals who care for perinatal hospice
      mothers can affirm their motherhood through their behavior and attitudes.

PMID- 21884235
TI  - Traveling through time to normal birth.

PMID- 21884236
TI  - Letter from Europe: kick-starting the uterus.

PMID- 21884237
TI  - Pregnancy, childbirth and the newborn: the complete guide.

PMID- 21884239
TI  - When is the best age to have a child?

PMID- 21884243
TI  - No more pilots, a phase III trial of fibrates in primary biliary cirrhosis is
      long overdue!

PMID- 21884244
TI  - Nutritional considerations in end-stage liver disease.

PMID- 21884245
TI  - Interleukin-28B genetic variations and response to interferon-based therapy:
      Asian perspectives.

PMID- 21884246
TI  - Autoimmune pancreatitis.
AB  - The purpose of this review is to provide a concise view of the existing knowledge
      of autoimmune pancreatitis (AIP) for practicing clinicians. AIP is a rare disease
      whose recognition and understanding are evolving. It is a type of chronic
      pancreatitis that often presents as obstructive jaundice, has a distinctive
      histology, and is exquisitely sensitive to steroid therapy. This form of chronic
      pancreatitis has a unique clinical, biochemical, and radiological profile. The
      term "AIP" encompasses two subtypes: types 1 and 2. Type 1 AIP is the pancreatic
      manifestation of a systemic fibro-inflammatory disease called immunoglobulin G4
      associated systemic diseases. Type 2 AIP has been shown to be associated with
      inflammatory bowel disease. Existing criteria are geared towards the diagnosis of
      type 1 AIP. At present, pancreatic histology is a requirement for the definitive
      diagnosis of type 2 AIP. AIP can mimic most other pancreatic diseases in its
      presentation, but in clinical practice, it often has to be differentiated from
      pancreatic cancer. There are established criteria and algorithms not only to
      diagnose AIP, but also to differentiate it from pancreatic cancer. The utility of
      these algorithms and the approach to management are discussed here.

PMID- 21884247
TI  - Suppressive effects of entecavir on hepatitis B virus and hepatocellular
      carcinoma.
AB  - BACKGROUND AND AIM: We investigated the efficacy and effectiveness of entecavir
      in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients.
      METHODS: We enrolled 231 nucleoside-naive chronic hepatitis B (CHB) patients
      primarily treated with entecavir 0.5 mg/day for at least 6 months in our
      institution. Of these, 71 patients had HCC at the start of entecavir treatment
      (HCC group) and 160 did not (non-HCC group). We compared antiviral responses to
      entecavir in the two groups, and evaluated the effects of entecavir on the
      clinical outcomes of curatively-treated HCC patients. RESULTS: The HCC and non
      HCC groups had similar cumulative rates of HBV-DNA negativity, alanine
      aminotransferase normalization, and hepatitis e antigen loss in year 2 (100% vs
      95.4%, 94.7% vs 97.3%, and 40.8% vs 41.8%, respectively; P > 0.05). Entecavir
      treatment for 12 months decreased mean Model for End-Stage Liver Disease scores
      in patients with cirrhosis and HCC (7.2 vs 5.6, P < 0.001). Of the 71 HCC
      patients, 16 underwent curative therapies concurrently with entecavir;
      hepatectomy in six and radiofrequency ablation in 10, and the 55 remaining
      patients received transarterial chemoembolization or conservative treatment. In a
      subgroup of 16 HCC patients receiving curative treatments, patients who became
      serum HBV DNA negative by week 24 had better overall survival (P = 0.039), but
      not recurrence-free survival (P = 0.961), than those who did not. CONCLUSIONS:
      First-line entecavir monotherapy is comparably effective in CHB patients with and
      without HCC, and improves hepatic function in HBV-related HCC patients. An early
      virological response to entecavir is prognostic of improved survival following
      curative therapy against HBV-related HCC.

PMID- 21884248
TI  - Outcomes after curative treatment for cryptogenic cirrhosis-associated
      hepatocellular carcinoma satisfying the Milan criteria.
AB  - BACKGROUND AND AIM: The prognosis of cryptogenic cirrhosis-associated
      hepatocellular carcinoma (CC-HCC) was reported to be poor because many of them
      were discovered at the advanced stage. The aim of this study is to reveal the
      clinical features of early CC-HCC. METHODS: Consecutive 36 curatively treated CC
      HCC patients satisfying the Milan Criteria were compared with corresponding 211
      HCV-associated HCC (HCV-HCC) patients. The clinical background, tumor recurrence
      rate, overall survival rate, and prognostic values of the patients were assessed.
      RESULTS: The size of CC-HCCs was larger than that of HCV-HCCs (P = 0.01). The
      respective tumor recurrence rates at 1, 3, and 5 years were 11%, 32%, and 46% in
      the CC-HCC, and 21%, 59%, and 81% in the HCV-HCC. The respective overall survival
      rates at 1, 3, and 5 years were 94%, 85%, and 80% in the CC-HCC, and 98%, 81%,
      and 61% in the HCV-HCC. CC-HCC patients had a lower tumor recurrence rate and a
      higher survival rate compared to the HCV-HCC patients (P = 0.001 and P = 0.02,
      respectively). Via multivariate analysis, significant factors for high recurrence
      rate were number of HCCs (P = 0.02) and serum alpha fetoprotein levels (P = 0.03)
      in CC-HCC, whereas multiple tumors (P < 0.001), large tumor size (P = 0.01), and
      high alanine aminotransferase (P = 0.04) in HCV-HCC. The factor for survival was
      albumin in both groups. CONCLUSION: The size of CC-HCC was larger than that of
      HCV-HCC even in patients who received curative treatment; however, the risk for
      recurrence and the mortality of the patients with CC-HCC was lower than those
      with HCV-HCC.

PMID- 21884249
TI  - Education and imaging. Gastrointestinal: gallbladder carcinoma and
      cholelithiasis: a radiologic--pathologic correlation.

PMID- 21884250
TI  - Education and imaging. Gastrointestinal: esophageal melanocytosis--the esophagus
      that seemed "off-color".

PMID- 21884251
TI  - Education and imaging. Gastrointestinal: fasciolopsis buski infestation diagnosed
      by upper gastrointestinal endoscopy.

PMID- 21884252
TI  - Education and imaging. Hepatobiliary and pancreatic: traumatic bile duct neuroma.

PMID- 21884253
TI  - Education and imaging. Hepatobiliary and pancreatic: bile duct stricture after
      cholecystectomy.

PMID- 21884255
TI  - Iconography in Bradshaw rock art: breaking the circularity.
AB  - BACKGROUND: Interpreting the symbols found in the rock art of an extinct culture
      is hampered by the fact that such symbols are culturally determined. How does one
      break the circularity inherent in the fact that the knowledge of both the symbols
      and the culture comes from the same source? In this study, the circularity is
      broken for the Bradshaw rock art of the Kimberley by seeking anchors from outside
      the culture. METHODS: Bradshaw rock art in the Kimberley region of Australia and
      Sandawe rock art in the Kolo region of Eastern Tanzania were surveyed in six
      visits on foot, by vehicle, by helicopter and from published or shared images, as
      well as from the published and online images of Khoisan rock art. RESULTS:
      Uniquely shared images between Bradshaw and Sandawe art, such as the 'mushroom
      head' symbol of psilocybin use, link the two cultures and indicate that they were
      shamanistic. Therefore, many mysterious features in the art can be understood in
      terms of trance visualisations. A number of other features uniquely link Bradshaw
      and Sandawe cultures, such as a special affinity for small mammals. There are
      also many references to baobabs in early Bradshaw art but not later. This can be
      explained in the context of the Toba super-volcano, the likely human transport of
      baobabs to the Kimberley and the extraordinary utility of the baobab. CONCLUSION:
      Many more mysterious symbols in Bradshaw rock art might await interpretation
      using the approaches adopted here.

PMID- 21884256
TI  - Influence of corneal astigmatism, corneal curvature and meridional differences on
      corneal hysteresis and corneal resistance factor.
AB  - BACKGROUND: This study investigated the influence of corneal astigmatism, corneal
      curvature and meridional differences on corneal hysteresis (CH) and the corneal
      resistance factor (CRF) in a group of normal Chinese persons. METHODS: Ninety
      five participants were recruited and data from the eye with higher corneal
      astigmatism were analysed. The anterior corneal curvature was measured by corneal
      topography. The Goldmann-correlated intraocular pressure (IOPg), corneal
      compensated intraocular pressure (IOPcc), CH and CRF at different meridians
      (default horizontal position, 10 degrees , 20 degrees  and 30 degrees  along the
      superotemporal and inferonasal meridians) were obtained from an ocular response
      analyser. The corneal powers at these specific meridians also were calculated.
      RESULTS: At the default position, the IOPg and CRF had weak correlations with
      corneal astigmatism, while the IOPcc and CH were not significantly correlated
      with corneal astigmatism. Both the IOPg and IOPcc were measured significantly
      higher at the default position. The CH and CRF were lower at the default position
      but the difference in the CRF from obliquity could not reach statistical
      significance. The CH was not significantly correlated with the corneal power at
      all meridians. The CRF correlated with the corneal power only at 30 degrees 
      superotemporal. CONCLUSION: Corneal astigmatism and head tilt did not have much
      effect on the measurement of CH and the CRF, both of which were lowest along the
      horizontal meridian. Clinically, the difference was small. The influence of
      corneal power on CH and the CRF was minimal.

PMID- 21884257
TI  - The Man from Ironbark: a profile of Professor Jack Pettigrew FRS, flamboyant
      sensory systems researcher and recipient of the H Barry Collin Research Medal.

PMID- 21884259
TI  - Induction of Sca-1 in the duct cells of the mouse submandibular gland by
      obstruction of the main excretory duct.
AB  - The effect of ligation of the main excretory duct (MED) of the mouse
      submandibular gland (SMG) on the expression of Sca-1, a stem cell antigen, was
      examined by Western blotting and immunohistochemistry. By Western blotting, the
      expression of Sca-1 with a molecular weight of 18 kDa was identified in the
      normal gland. At 1 day post-ligation, the expression level of Sca-1 was strongly
      increased in the experimental gland and weakly in the contralateral gland, and
      such expression in both glands decreased at 6 days. By immunohistochemistry, Sca
      1 was detected weakly in the apical membrane of excretory duct (ED) cells of the
      SMG under the normal condition. By duct ligation, Sca-1 became expressed strongly
      in most cells of the two major duct systems, i.e., the striated duct (SD) and
      granular convoluted tubules (GCT), but was not detected in the acinar (Ac) cells.
      By fluorescence-activated cell sorter (FACS) analysis, the number of side
      population (SP) cells in this gland was found to be increased by ligation. These
      results imply that Sca-1-positive cells may have a role in the duct cell
      proliferation in the regeneration step elicited by MED ligation-induced injury.

PMID- 21884261
TI  - Editorial Comment to Risk factors for pelvic lymphoceles post-radical
      prostatectomy.

PMID- 21884266
TI  - VIIth International Conference on Boar Semen Preservation, 14-17 August 2011,
      Bonn, Germany.

PMID- 21884268
TI  - Review on international trade with boar semen.
AB  - For more than 40 years, AI (artificial insemination) has been carried out with
      pigs. In some countries, it constitutes since the 1990 s the dominant procedure
      with piglet production to fertilize the sow. This procedure of insemination with
      fresh semen has become prevalent in all countries on a worldwide basis with an
      important pig meat production, with the exception of China. Meanwhile, up to 90%
      of the sows have been artificially inseminated. The trend is still upwards. As
      the need of pig meat and thus the production continues to increase, one can
      proceed on the assumption that the number of semen doses, which is necessary for
      this procedure, will likewise increase correspondingly. Until now, the trade
      beyond borders has only been marginal. An improvement in the sense of a longer
      shelf life for semen doses is indispensable for the trade over longer distances.

PMID- 21884269
TI  - The current value of frozen-thawed boar semen for commercial companies.
AB  - Opportunities for use of frozen-thawed semen (FTS) must address genetic
      advancement and fertility for developing practical models for use. Concerns about
      slowed genetic gains, lowered fertility and additional costs may limit use of
      FTS. However, FTS is presently used for international exchange among nucleus
      farms to help maintain genetic diversity. Use of FTS beyond several days can
      provide increased flexibility for on-farm use and allow additional time for
      disease tests. There may be potential for use of FTS for short-term banking
      during periods of low demand and while sires await breeding value tests.
      Opportunities exist for FTS use in long-term banking of sire lines, creation of
      semen pools for genetic progress evaluation and for use in emergencies. Advancing
      FTS technology will require the following: (i) more efficient production of
      doses; (ii) improved fertility with single sire or pooled matings; (iii)
      education and training; and (iv) models for FTS use and economics for use under
      various scenarios.

PMID- 21884270
TI  - Capacitation and capacitation-like sperm surface changes induced by handling boar
      semen.
AB  - Since it has been well recognized that reproductive technologies, such as
      cryopreservation and sex-sorting, have a detrimental impact on sperm quality.
      These procedures cause sperm membrane destabilization which resembles that of
      capacitation. The pathways of this complex biochemical event are slowly
      unravelling, including the vital role of coating and decoating factors on the
      sperm surface. Characterization of these factors is leading to the development of
      novel surface manipulation techniques to stabilize the sperm membrane during
      handling. The possible application of these for assisted pig reproduction is
      discussed.

PMID- 21884271
TI  - Colloid centrifugation of boar semen.
AB  - Colloid centrifugation of boar semen has been reported sporadically for at least
      the last two decades, beginning with density gradient centrifugation (DGC) and
      progressing more recently to single layer centrifugation (SLC). Single layer
      centrifugation through a species-specific colloid has been shown to be effective
      in selecting the best spermatozoa (spermatozoa with good motility and normal
      morphology) from boar sperm samples. The method is easier to use and less time
      consuming than DGC and has been scaled-up to allow whole ejaculates from other
      species, e.g. stallions, to be processed in a practical manner. The SLC technique
      is described, and various scale-up versions are presented. The potential
      applications for SLC in boar semen preservation are as follows: to improve sperm
      quality in artificial insemination (AI) doses for 'problem' boars; to increase
      the shelf-life of normal stored sperm samples, either by processing the fresh
      semen before preparing AI doses or by processing the stored semen dose to extract
      the best spermatozoa; to remove pathogens (viruses, bacteria), thus improving
      biosecurity of semen doses and potentially reducing the use of antibiotics; to
      improve cryosurvival by removing dead and dying spermatozoa prior to
      cryopreservation; to select spermatozoa for in vitro fertilization. These
      applications are discussed and practical examples are provided. Finally, a few
      thoughts about the economic value of the technique to the boar semen industry are
      presented.

PMID- 21884272
TI  - Antioxidant mechanisms and their benefit on post-thaw boar sperm quality.
AB  - While being an important component of normal cellular function, excess levels of
      reactive oxygen species (ROS) cause cell damage and death. The ability to protect
      sperm against oxidative damage is of particular importance in the artificial
      reproduction industry because of the increased production of ROS by the sperm
      cell during processing. This review discusses the formation of ROS and the use of
      antioxidants in protecting boar sperm against oxidative damage.

PMID- 21884273
TI  - Plenary contribution to International Conference on Boar Semen Preservation 2011.
      Genetic selection for freezability and its controversy with selection for
      performance.
AB  - Little data are available in the literature regarding freezability of boar sperm
      or its relationship with other traits. Existing data suggest the trait would
      respond favourably to selection, and information is available from other species
      suggesting components that might have changed. Genetic parameters are estimated
      for boar sperm freezability including heritability and correlations with other
      production traits. Sperm freezability is an ideal candidate for marker assisted
      selection or selection for favourable alleles.

PMID- 21884274
TI  - International Conference on Boar Semen Preservation (ICBSP): the first 25 years.
AB  - The International Conference on Boar Semen Preservation (ICBSP) has been in
      existence for 25 years. During that time, six conferences have been held in
      Europe and North America. Each conference has sought to communicate research
      advances in pig semen technology and artificial insemination (AI). Clearly, the
      conference has been a catalyst for the advancement of various improvements in
      semen preservation and AI. In addition, the conference has served to initiate
      collaboration among scientists worldwide. A summary of problems that remain to be
      investigated and solved in swine semen technology is provided.

PMID- 21884275
TI  - Stress and dietary factors modify boar sperm for processing.
AB  - This paper reviews stresses boar sperm undergo during processing and presents
      preliminary results of dietary modification that minimize this damage. Processing
      for artificial insemination (AI) stresses boar sperm by osmotic effects; altering
      cell size, shape and membranes; intracellular ice formation; and production of
      reactive oxygen species (ROS). Sperm response to ROS is concentration-dependent,
      with low levels activating the ERK pathway to stimulate tyrosine phosphorylation
      (Tyr-P) and capacitation, but high concentrations or inappropriately timed onset
      of ROS pathways can harm sperm. Fresh boar sperm exposed to ROS increased
      intracellular hydrogen peroxide (H(2) O(2) ) phospholipase and lipid
      peroxidation, maintained viability but lost motility and underwent acrosome
      reactions (AR). Direct incorporation of lipids +/- the antioxidant Vitamin E
      improves the survival of liquid- and frozen-stored semen. Boars fed dietary
      flaxseed for 8 weeks to increase n-3 fatty acids displayed improved sperm
      morphology (p < 0.05), increased membrane fluidity (p < 0.05) and better
      retention of motility and viability during 5-7 day storage (p < 0.05). Processes
      reducing oxidative damage to stored sperm should be evaluated.

PMID- 21884276
TI  - Assessment of storage effects in liquid preserved boar semen.
AB  - Fertility of extended boar semen declines within the first 72 h of storage in
      vitro. Standard semen assessment, such as motility and membrane integrity, allows
      detection of lethal damage of spermatozoa. However, conventional sperm assessment
      often lacks standardization and does not allow identification of sub-lethal
      changes of sperm quality during the initial 72 h of storage. In the present brief
      review, recent strategies for quality assessment of liquid preserved boar semen
      are discussed and basic implications for experiments designed to detect storage
      effects are given.

PMID- 21884277
TI  - Do CASA systems satisfy consumers demands? A critical analysis.
AB  - Boar studs are often offered new technologies including several CASA (computer
      assisted semen analysis) systems. However, independent information to assist
      their purchase decisions is not available. The systems accuracy and repeatability
      variation because of different factors can be evaluated through duplicate testing
      of semen samples and comparison of the results according to WHO standards for
      humans. This primary analysis and a thorough economic cost benefit evaluation
      will help to decide whether the purchase of a CASA system will be profitable for
      a boar stud. Our experience of implementing several CASA systems in the
      cooperative Dutch Artificial Insemination (AI) centres is used as a base for this
      discussion.

PMID- 21884278
TI  - New aspects of boar sperm encapsulation.
AB  - The study takes into account the main steps and techniques for boar semen
      encapsulation, to optimize the instrumental insemination interventions. The use
      of cheap, biocompatible polymers as alginate can assure a regular, constant
      release of spermatozoa in the sow reproductive system, avoiding the double/triple
      intervention of insemination and reducing the employ of disposable materials. The
      encapsulation/microencapsulation of semen can therefore be the starting point of
      new, innovative systems of pig reproduction management.

PMID- 21884279
TI  - Biological markers of boar fertility.
AB  - The semen evaluation techniques used in most commercial artificial insemination
      centers, which includes sperm motility and morphology measurements, provides a
      very conservative estimate of the relative fertility of individual boars. As
      well, differences in relative boar fertility are masked by the widespread use of
      pooled semen for commercial artificial insemination (AI) in many countries.
      Furthermore, the relatively high sperm numbers used in commercial AI practice
      usually compensate for reduced fertility, as can be seen in some boars when lower
      numbers of sperm are used for AI. The increased efficiency of pork production
      should involve enhanced use of boars with strong reproductive efficiency and the
      highest genetic merit for important production traits. Given that the current
      measures of semen quality are not always indicative of fertility and reproductive
      performance in boars, accurate and predictive genetic and protein markers are
      still needed. Recently, significant efforts have been made to identify reliable
      markers that allow for the identification and exclusion of sires with reduced
      reproductive efficiency. This paper reviews the current status of proteomic and
      genomic markers of fertility in boars in relation to other livestock species.

PMID- 21884280
TI  - Field data analysis of boar semen quality.
AB  - This contribution provides an overview of approaches to correlate sow fertility
      data with boar semen quality characteristics. Large data sets of fertility data
      and ejaculate data are more suitable to analyse effects of semen quality
      characteristics on field fertility. Variation in fertility in sows is large. The
      effect of semen factors is relatively small and therefore impossible to find in
      smaller data sets. Large data sets allow for statistical corrections on both sow-
      and boar-related parameters. Remaining sow fertility variation can then be
      assigned to semen quality parameters, which is of huge interest to AI (artificial
      insemination) companies. Previous studies of Varkens KI Nederland to find the
      contribution to field fertility of (i) the number of sperm cells in an
      insemination dose, (ii) the sperm motility and morphological defects and (iii)
      the age of semen at the moment of insemination are discussed in context of the
      possibility to apply such knowledge to select boars on the basis of their sperm
      parameters for AI purposes.

PMID- 21884281
TI  - The potential risk of infectious disease dissemination via artificial
      insemination in swine.
AB  - Artificial insemination (AI) is one of the most widely used assisted reproductive
      technologies in swine. To maintain a healthy semen trade, it is crucial that
      diligence be given to managing and minimizing the chance of extended semen
      playing an epidemiological role in the transmission of infectious disease. In
      swine, pathogens of primary importance, which may be transmitted through semen
      include Aujeszky's disease, brucellosis, chlamydophilosis, porcine circovirus
      type 2, classical swine fever, Japanese encephalitis, leptospirosis, parvovirus,
      porcine reproductive and respiratory syndrome, rubulavirus, foot-and-mouth
      disease and swine vesicular disease. This paper will summarise the current state
      of knowledge pertaining to these pathogens in relation to swine AI.

PMID- 21884282
TI  - Mechanisms of sperm storage in the female reproductive tract: an interspecies
      comparison.
AB  - Once semen has been collected for artificial insemination, it is diluted into
      extenders designed to prevent its deterioration over the period prior to
      insemination. If the semen is not frozen, the extenders provide protection for a
      period of a few hours to a few days, depending on species. Despite the efforts of
      biotechnologists to increase the duration of storage without compromising
      fertility, there has been relatively little progress for many years. However,
      comparative studies in diverse species have revealed that long-term sperm storage
      (up to months and years) within the female reproductive tract is relatively
      commonplace in reptiles, fishes, birds and amphibians. Even among mammals, some
      species of bat have evolved mechanisms for storing spermatozoa for several months
      in the uterus or oviduct so that they can mate in the autumn but postpone
      fertilization until the spring. We currently know little about the mechanisms
      that support such long-term sperm storage, mainly because evidence from such
      species is either absent or fragmentary. Nevertheless, parallels between
      mammalian and other systems, where spermatozoa are sequestered in sperm storage
      tubules, suggest that the enclosure of spermatozoa within pockets of epithelial
      cells may be sufficient to achieve long-term sperm storage. In addition, recent
      evidence from sperm-storing bats has suggested an alternative, or additional,
      hypothesis that the modulation of apoptosis within epithelial cells is important
      in controlling sperm survival. Despite a lack of direct experimental evidence
      from a wide variety of species, I propose that there is now enough evidence to
      warrant investigation of these hypotheses.

PMID- 21884283
TI  - Maternal communication with gametes and embryo: a personal opinion.
AB  - Maternal communication with gametes and embryo remains to be an important
      research subject in reproductive biology. This is mainly because of the central
      role that events taking place during this period play in establishment of
      pregnancy and creation of an offspring. The benefits of understanding how gametes
      and embryo communicate with maternal tract are not limited to improving
      conception rates or better fertility. It is apparent that gametes and embryo
      interactions form the basis of the periconceptional environment. These events
      play a major role in forming the epigenetic profile of an individual, influencing
      its development and health in adulthood. In this paper, I will describe some
      ideas and opinions on the new strategies and tools needed for further
      understanding of maternal communication with gametes and embryo.

PMID- 21884286
TI  - Oral nutritional support in patients with cancer of the gastrointestinal tract.

PMID- 21884284
TI  - Approaches towards efficient use of boar semen in the pig industry.
AB  - The current cervical artificial insemination (CAI) procedure, involving
      deposition of excessive sperm numbers, is uneconomical for pig industry. The most
      obvious alternative requires uterine deposition in combination with fixed-time
      AI, which would reduce the number of sperm required per pregnant sow, thus
      allowing the best use of valuable boars and, ultimately, the commercial
      integration of frozen-thawed and sexed sperm. This review depicts possible best
      ways to implement an efficient use of liquid-stored, frozen-thawed and sexed
      sperm by the pig industry.

PMID- 21884287
TI  - Sustained benefits of a community dietetics intervention designed to improve oral
      nutritional supplement prescribing practices.
AB  - BACKGROUND: Healthcare professionals working in the community do not always
      prescribe oral nutritional supplements (ONS) according to best practice
      guidelines for the management of malnutrition. The present study aimed to
      determine the impact of a community dietetics intervention on ONS prescribing
      practices and expenditure 1 year later. METHODS: The intervention involved
      general practitioners (GPs), practice nurses, nurses in local nursing homes and
      community nurses. It comprised an education programme together with the provision
      of a new community dietetics service. Changes in health care professionals'
      nutrition care practices were determined by examining community dietetics
      records. ONS prescribing volume and expenditure on ONS were assessed using data
      from the Primary Care Reimbursement Service of the Irish Health Service
      Executive. RESULTS: Seven out of 10 principal GPs participated in the nutrition
      education programme. One year later, screening for malnutrition risk was better,
      dietary advice was provided more often, referral to the community dietetics
      service improved and ONS were prescribed for a greater proportion of patients at
      'high risk' of malnutrition than before (88% versus 37%; P < 0.001). There was a
      trend towards fewer patients being prescribed ONS (18% reduction; P = 0.074) and
      there was no significant change in expenditure on ONS by participating GPs (3%
      reduction; P = 0.499), despite a 28% increase nationally by GPs on ONS.
      CONCLUSIONS: The community dietetics intervention improved ONS prescribing
      practices by GPs and nurses, in accordance with best practice guidelines, without
      increasing expenditure on ONS during the year after intervention.

PMID- 21884288
TI  - Dietetic practice in refeeding syndrome.
AB  - BACKGROUND: The physiology and consequences of refeeding syndrome have long been
      recognised, although its management continues to be debated, despite the
      recommendations made by The National Institute for Health and Clinical Excellence
      (NICE) in their guideline 'Nutrition Support in Adults' (2006). The present study
      aims to assess current dietetic opinion and practice in this area, as well as
      whether the NICE recommendations have been adopted. METHODS: An anonymous, self
      completed Internet survey was designed investigating current practice and
      opinions on the NICE (2006) guidance on this subject. A link to the questionnaire
      was distributed with a covering letter via e-mail to the heads of department of
      National Health Service Trusts in the London region, UK, requesting that it be
      disseminated to all dietitians working with adults. After the closing date, all
      responses were collated and analysed. RESULTS: The survey elicited a 30.8%
      response rate. Some 89.8% of respondents have read the NICE guidance on Nutrition
      Support in Adults (2006) and 66.9% have changed their practice regarding
      refeeding syndrome management as a result. Sixty-two percent do not wait for
      biochemistry to normalise before commencing nutrition. Ninety-two percent of
      respondents completed the mini case studies indicating that current practice is
      inconsistent among dietitians. Neither NICE criteria for recognising patients at
      risk of refeeding, nor the recommended starting rates are universally followed.
      Seventy-five percent continue to supplement electrolytes reactively. CONCLUSIONS:
      Although limited by a small sample size, the findings of the present study
      suggest that dietetic practice regarding refeeding syndrome management remains
      inconsistent with the recommendations made by NICE, although some aspects have
      been adopted.

PMID- 21884290
TI  - Shedding light on the evolution of plasticity in natural populations.
AB  - Plasticity allows for changes in phenotype in response to environmental cues,
      often facilitating local adaptation to seasonal environments. Phenotypic
      plasticity alone, however, may not always be sufficient to ensure adaptation to
      new localities. In particular, changing cues associated with shifting seasonal
      regimes may no longer induce appropriate phenotypic responses in new environments
      (Nicotra et al. 2010). Plastic responses must thus evolve to avoid being
      maladaptive. To date, the extent to which plastic responses can change and the
      genetic mechanisms by which this can happen have remained elusive. In this issue
      of Molecular Ecology, Blackman et al. (2011a) harness natural variation in
      flowering time among populations of the wild sunflower, Helianthus annuus, to
      demonstrate that plasticity has indeed evolved in this species. Remarkably, they
      are able to detect changes in gene expression that are associated with both a
      loss of plasticity and a reversal of the plastic response. These changes occur in
      two separate, but integrated, regulatory pathways controlling the transition to
      flowering, suggesting that complex regulatory networks that incorporate multiple
      environmental and developmental cues may facilitate the evolution of plastic
      responses. This study leverages knowledge from plant genetic models to provide a
      surprising level of insight into the evolution of an adaptive trait in a non
      model species. Through discoveries of the roles of gene duplication and network
      modularity in the evolution of plastic responses, the study raises questions
      about the degree to which species-specific network architectures may act as a
      constraint to the potential of adaptation.

PMID- 21884291
TI  - Evolutionary potential in the wild: more than meets the eye.
AB  - The genus Aquilegia consists of 60-70 perennial plant species widely distributed
      throughout the northern hemisphere. Its flowers have a delicate and ornamental
      appearance that makes them a favourite of gardeners. In this genus, adaptive
      radiations for both floral and vegetative traits have occurred. These adaptive
      radiations, and the key phylogenetic placement of Aquilegia between Arabidopsis
      and rice, make this genus a 'model system' for plant evolution (Kramer 2009). In
      this issue, Castellanos et al. (2011) use a marker-based method to infer
      heritability for floral and vegetative traits in two Aquilegia species. Layered
      on top of this are estimates of the strength of natural selection. This novel
      joint estimation of heritability and selection in the wild showed that vegetative
      traits, compared to floral traits, have the highest evolutionarily potential.
      Evolutionary potential is the most important quantity to measure in wild
      populations. It combines inheritance and strength of selection and predicts the
      potential for populations to adapt to changing environments. The combination of
      molecular techniques with species in natural environments makes this work a model
      for molecular ecological investigations.

PMID- 21884292
TI  - Vertical and horizontal transmission drive bacterial invasion.
AB  - A huge variety of Arthropod species is infected with endosymbiotic Wolbachia
      bacteria that manipulate their host's reproduction to invade populations. In
      addition to vertical transmission from mother to offspring through the egg
      cytoplasm, it has been demonstrated through phylogenetic analyses and natural
      transfer experiments that horizontal transmission of Wolbachia (i.e. contagion)
      can occur between Arthropod hosts. More recently, factors influencing horizontal
      transfer have also been explored. While it is clear that horizontal transmission
      between species plays a major role in the evolutionary history of Wolbachia
      infections among insects, its role in the spread of a new infection through a
      host population, notably through within-species transfers, remained unknown. In
      this issue of Molecular Ecology, Kraaijeveld et al. (2011) present the first
      evidence that horizontal transmission played a key role in the early spread of
      parthenogenesis-inducing Wolbachia through the parasitoid wasp Leptopilina
      clavipes. To support their finding, the authors studied genetic variation in
      three types of markers, including host nuclear DNA, mitochondrial DNA and
      Wolbachia DNA. Specifically, they examined potential associations between their
      diversity patterns. No diversity was detected in Wolbachia genes, indicating that
      a single Wolbachia strain must have infected and spread through L. clavipes. In
      addition, a correlation between substantial variation in mitochondrial and
      nuclear genotypes suggested that horizontal transmission played an important role
      in the current clonal genetic variation in this wasp. Such horizontal
      transmission could be facilitated by a specific host ecology (e.g. parasitoid
      wasps sharing the same host resource) and potentially impact co-evolution between
      host and symbiont.

PMID- 21884293
TI  - Infections and pregnancy: from a dream to a nightmare.

PMID- 21884294
TI  - Intracellular bacteria and adverse pregnancy outcomes.
AB  - This review considers the role of intracellular bacteria in adverse pregnancy
      outcomes, such as miscarriage, stillbirths, and preterm labour. The cause of
      miscarriage, stillbirth and preterm labour often remains unexplained.
      Intracellular bacteria that grow either poorly or not at all on media used
      routinely to detect human pathogens could be the aetiological agents of these
      obstetric conditions. For example, Listeria monocytogenes and Coxiella burnetti
      are intracellular bacteria that have a predilection for the fetomaternal unit and
      may induce fatal disease in the mother and/or fetus. Both are important foodborne
      or zoonotic pathogens in pregnancy. Preventive measures, diagnostic tools and
      treatment will be reviewed. Moreover, we will also address the importance in
      adverse pregnancy outcomes of other intracellular bacteria, including Brucella
      abortus and various members of the order Chlamydiales. Indeed, there is growing
      evidence that Chlamydia trachomatis, Chlamydia abortus and Chlamydia pneumoniae
      infections may also result in adverse pregnancy outcomes in humans and/or
      animals. Moreover, newly discovered Chlamydia-like organisms have recently
      emerged as new pathogens of both animals and humans. For example, Waddlia
      chondrophila, a Chlamydia-related bacterium isolated from aborted bovine fetuses,
      has also been implicated in human miscarriages. Future research should help us to
      better understand the pathophysiology of adverse pregnancy outcomes caused by
      intracellular bacteria and to determine the precise mode of transmission of newly
      identified bacteria, such as Waddlia and Parachlamydia. These emerging pathogens
      may represent the tip of the iceberg of a large number of as yet unknown
      intracellular pathogenic agents.

PMID- 21884295
TI  - Full genomic analyses of human rotavirus G4P[4], G4P[6], G9P[19] and G10P[6]
      strains from North-eastern India: evidence for interspecies transmission and
      complex reassortment events.
AB  - In hospitalized patients with acute gastroenteritis in Manipur, India, four
      rotavirus strains were found to possess VP7 and/or VP4 genes with porcine or
      bovine characteristics. Considering the animal-like nature of these strains, the
      remaining eight gene segments were analysed to decipher their exact origin.
      Analyses of full genome of these strains exhibited their origin from
      porcine/bovine rotaviruses. This study suggests single or multiple events of
      reassortment involving multiple gene segments of more than one host type among
      the strains and emphasizes the significance of complete genetic characterization
      of unusual strains in regions with high incidence and mortality rates.

PMID- 21884297
TI  - Femoral vein as bypass graft for subclavian venous occlusion in a haemodialysis
      patient.

PMID- 21884296
TI  - European expert opinion on the management of invasive candidiasis in adults.
AB  - This report discusses the present status of antifungal therapy and treatment
      options for candidaemia, considered by experts in the field in Europe. A
      conference of 26 experts from 13 European countries was held to discuss
      strategies for the treatment and prevention of invasive candidiasis, with the aim
      of providing a review on optimal management strategies. Published and unpublished
      comparative trials on antifungal therapy were analysed and discussed. Commonly
      asked questions about the management of candidaemia were selected, and possible
      responses to these questions were discussed. Panellists were then asked to
      respond to each question by using a touchpad answering system. After the initial
      conference, the viewpoint document has been reviewed and edited to include new
      insights and developments since the initial meeting. For many situations,
      consensus on treatment could not be reached, and the responses indicate that
      treatment is likely to be modified on a patient-to-patient basis, depending on
      factors such as degree of illness, prior exposure to azole antifungals, and the
      presence of potentially antifungal drug-resistant Candida species.

PMID- 21884298
TI  - A young woman with fever, weight loss and a renal mass.

PMID- 21884299
TI  - Molecular pathology of tumor-initiating cells: lessons from Philadelphia
      chromosome-positive leukemia.
AB  - Recent improvements in cell purification and transplantation techniques have
      contributed to the identification of cell populations known as tumor-initiating
      cells (TIC). This discovery has led to the 'cancer stem cell hierarchy' concept,
      which holds that tumors are organized as a hierarchy of malignant tissues
      sustained by such TIC. However, this concept remains controversial. In this
      review, we examine recent advances in cancer stem cell research that have been
      generated from studies of Philadelphia (Ph) chromosome-positive leukemia. The
      abnormal Ph chromosome, which arises from a translocation creating the BCR-ABL1
      fusion gene, is most commonly associated with chronic myelogenous leukemia (CML)
      and precursor B cell acute lymphoblastic leukemia (B-ALL). Examination of the
      pathophysiology of these diseases has provided interesting insights into not only
      the hierarchy of leukemia stem cells but also their clonal evolution. Both shared
      and unique regulatory mechanisms affecting normal and CML stem cell behavior have
      been identified. On the other hand, genetic diversity in specific clones of Ph(+)
      B-ALL that drive clonal evolution has recently come to light. Our expanding
      knowledge of the biology of TIC contributes to the progress of cancer research,
      and may open the door to new concepts in cancer therapy.

PMID- 21884300
TI  - Variant alveolar lipoproteinosis: a syndrome with distinct clinical and
      pathological features.
AB  - Pulmonary alveolar proteinosis (PAP) is a rare condition in which pulmonary
      macrophages fail to clear surfactant, resulting in the alveolar accumulation of
      lipoproteinaceous debris. The histopathology of PAP is typified by diffuse
      filling of terminal airways with eosinophilic, PAS/diastase (PAS/D)-positive
      acellular material. We present five patients who showed histopathological changes
      in the lungs consistent with mild PAP. However, these cases were notable for the
      abundance of degenerating alveolar macrophages, weak PAS staining of
      lipoproteinaceous material and paucity of lamellated bodies on ultrastructural
      examination. Only one patient showed the CT finding of mosaiform 'crazy-paving'
      and the opalescent bronchoalveolar lavage fluid characteristic of PAP. In one
      case, therapeutic lung lavage based on a presumptive diagnosis of PAP exacerbated
      respiratory distress. Three patients showed partial or near-complete resolution
      of disease in response to high-dose corticosteroid therapy, a treatment approach
      that is generally ineffective in PAP. We conclude that distinguishing 'variant
      alveolar lipoproteinosis' from classical PAP is clinically important. Despite the
      otherwise typical appearance of lipoproteinaceous alveolar material in lung
      biopsies, the presence of degenerating foamy macrophages and atypical
      histochemical, ultrastructural and radiographic features suggest a steroid
      responsive form of proteinosis that is likely pathogenetically distinct and may
      not be amenable to whole-lung lavage.

PMID- 21884301
TI  - Renal thrombotic microangiopathy associated with chronic graft-versus-host
      disease after allogeneic hematopoietic stem cell transplantation.
AB  - Thrombotic microangiopathy (TMA) is a major complication after hematopoietic stem
      cell transplantation (HSCT). In this study, we examined the clinical and
      pathologic features of 2 patients and 5 autopsy cases with HSCT-associated renal
      TMA to clarify the association between graft-versus-host disease (GVHD) and renal
      TMA. The median interval between HSCT and renal biopsy or autopsy was 7 months
      (range 3-42 months). Clinically, acute and chronic GVHD occurred in 7 and 4
      patients, respectively. Clinical evidence for TMA was detected in 2 patients,
      while chronic kidney disease developed in all patients. The main
      histopathological findings were diffuse endothelial injury in glomeruli,
      peritubular capillaries (PTCs), and small arteries. In addition, all cases showed
      glomerulitis, renal tubulitis, and peritubular capillaritis with infiltration of
      CD3+ T cells and TIA-1+ cytotoxic cells, suggesting that GVHD occurred during the
      development of TMA. Diffuse and patchy C4d deposition was noted in glomerular
      capillaries and PTCs, respectively, in 2 biopsy and 2 autopsy cases, suggesting
      the involvement of antibody-mediated renal endothelial injury in more than 50% of
      renal TMA cases. In conclusion, the kidney is a potential target of chronic GVHD
      that may induce the development of HSCT-associated TMA. Importantly, some cases
      are associated with chronic humoral GVHD.

PMID- 21884303
TI  - Solitary fibrous tumor of the prostate: a report of two cases.
AB  - We here report two cases of solitary fibrous tumor (SFT) arising in the prostate.
      Two men, 66 and 69 years old, with urinary tract symptoms were diagnosed with SFT
      on transrectal needle biopsy and transurethral resection of the prostate,
      respectively. The tumors were removed by a low anterior resection including
      tumor, prostate and rectum en bloc and cystoprostatectomy, respectively. Both
      tumors were well-circumscribed but also showed some infiltration of the prostate
      glands. They were composed of storiform bundles of bland spindle cells that
      stained strongly for CD34 and vimentin but negative for muscle markers. Although
      rare, SFT should be considered as differential diagnosis of spindle cell lesions
      on prostate biopsies.

PMID- 21884302
TI  - Macrophage polarization in the maculae of age-related macular degeneration: a
      pilot study.
AB  - Macrophages can be polarized to exhibit either pro-inflammatory M1 or pro
      angiogenic M2 phenotypes, but have high phenotypic plasticity. This pilot study
      investigated macrophage polarization in the macular retina and choroid of age
      related macular degeneration (AMD) and non-AMD subjects, as well as in AMD
      choroidal neovascular membranes (CNVM). All specimens were evaluated for routine
      histopathology. Quantitative real-time polymerase chain reaction for
      representative M1 (CXCL11) and M2 (CCL22) transcripts were performed on macular
      choroidal trephines (MCT) of 19 AMD and nine non-AMD eye bank eyes, on the
      microdissected macular retinal cells from the archived slides of five geographic
      atrophic AMD, five exudative/neovascular AMD, and eight normal autopsied eyes,
      and on microdissected inflammatory cells from two surgically removed CNVM that
      did not respond to anti-vascular endothelial growth factor (VEGF) therapy. High
      M2-chemokine transcript and a low ratio of M1 to M2 chemokine transcript were
      found in aging non-AMD MCT. Advanced AMD maculae had a higher M1 to M2 chemokine
      transcript ratio compared to normal autopsied eyes. Macrophages in the two CNVM
      of patients unresponsive to anti-VEGF therapy were polarized toward either M1 or
      M2 phenotypes. The number of M2 macrophages was increased compared to M1
      macrophages in normal aging eyes. A pathological shift of macrophage polarization
      may play a potential role in AMD pathogenesis.

PMID- 21884304
TI  - Renal carcinoma with (6;11)(p21;q12) translocation: report of an adult case.
AB  - An extremely rare adult example of renal carcinoma with t(6;11)(p21;q12 or q13)
      is presented here. The tumor of a 45-year-old Japanese male, excised under the
      diagnosis of renal cell carcinoma, was a well circumscribed 7 cm mass with light
      brown sectioned surfaces. Histologically, it was composed of a major population
      of large polygonal epithelioid cells in a nested alveolar growth and a
      subpopulation of smaller cells clustering around hyaline basement membrane
      material. The former cells possessed ample, clear to eosinophilic granular
      cytoplasm with well-defined cell borders and the latter was frequently
      accompanied by psammomatous calcification. These tumor cells exhibited
      immunoreactivity for melanoma markers, transcription factor EB and cathepsin K,
      but were not reactive for epithelial markers and transcription factor E3. While
      pulmonary metastatic foci that were noted preoperatively progressed rapidly
      following interferon-based therapy, subsequent sunitinib malate yielded a partial
      response and stabilized the lung metastasis for 6 months after surgery. We could
      trace 20 cases of 6p21 translocation renal carcinoma, among which only four were
      in individuals older than 40 years. Description of a new case like this is
      important since little is known about the prognosis and treatment of adult
      patients with this condition.

PMID- 21884305
TI  - Sarcoidosis with pulmonary hypertension exacerbated by Takayasu-like large vessel
      vasculitis.
AB  - A 72-year-old male visited the hospital with a complaint of dyspnea. Under the
      diagnosis of pulmonary hypertension (PH) due to chronic thrombotic and/or embolic
      disease, this patient received anti-coagulant therapy. Unfortunately, the
      respiratory state deteriorated and died 34 days after admission. At autopsy,
      noncaseating granulomas, which were diagnostic of sarcoidosis, were found in
      bilateral enlarged hilar lymph nodes, lungs, heart, liver, spleen, testis and
      epididymis. In pulmonary vasculature, the following three kinds of lesions were
      observed; (i) sarcoid granulomatous vasculitis at the peripheral arteries and
      veins, (ii) intimal fibrous lesions ubiquitously found in proximal and peripheral
      arteries which were thought to be organized thromboemboli, (iii) Takayasu-like
      large vessel vasculitis with a huge fresh mural thrombus narrowing the lumen of
      most proximal portion of right pulmonary artery. Autopsy findings indicate that
      chronic sustained PH state in this patient was attributable to thrombotic and/or
      thromboembolic disease, and Takayasu-like vasculitis with thrombus played a role
      in the final deterioration of respiratory state through exacerbation of PH. In
      sarcoidosis patients, vasculitic lesions which can be formed in both small and
      large pulmonary arteries must be raised as the differential diagnosis for the
      initial cause of PH as well as the accelerating factor of PH.

PMID- 21884306
TI  - Prostatic intraepithelial pagetoid histiocyte: a potential diagnostic pitfall.

PMID- 21884307
TI  - Chromophobe renal cell carcinoma with neuroendocrine differentiation and
      sarcomatoid change.

PMID- 21884308
TI  - Intravascular large B-cell lymphoma colonizing in senile hemangioma: a case
      report and proposal of possible diagnostic strategy for intravascular lymphoma.

PMID- 21884309
TI  - Maturation of EEG power spectra in early adolescence: a longitudinal study.
AB  - This study investigated the fine-grained development of the EEG power spectra in
      early adolescence, and the extent to which it is reflected in changes in peak
      frequency. It also sought to determine whether sex differences in the EEG power
      spectra reflect differential patterns of maturation. A group of 56 adolescents
      were tested at age 10 years and then at two further time-points approximately 18
      months apart. The EEG was recorded during both eyes-closed and eyes-open
      conditions and Fourier transformed to provide estimates of absolute and relative
      spectral power at 0.5 Hz intervals from 0.5 to 40 Hz. The peak alpha frequency
      for each individual at each time-point was also determined for relative spectral
      power. Partial Least Squares (PLS) analysis was used to determine the combination
      of electrodes and frequencies that showed developmental change, or differed
      between the sexes. As a function of age, absolute delta and theta frequencies
      power decreased, and relative alpha2 and beta frequencies increased, replicating
      the standard findings of a decrease in lower, and increase in higher, frequencies
      with age. A small but significant increase in peak alpha frequency with age was
      detected. Moreover PLS analysis performed with individual alpha frequencies
      aligned to 10 Hz suggested that the age-related increase seen in alpha2 relative
      power was driven by changes in the peak frequency. Although males demonstrated
      higher alpha power than females, there were no sex differences in peak frequency,
      suggesting that there may be more to sex differences in EEG power than simply
      different rates of maturation between the two sexes.

PMID- 21884310
TI  - Indirect goal priming is more powerful than explicit instruction in children.
AB  - This study examined the relative efficacy of explicit instruction and indirect
      priming on young children's behavior in a task that required a series of choices
      between a small immediate reward and a larger delayed reward. One hundread and
      six 4-year-old children were randomly assigned to one of four conditions
      involving one of two goals (maximize rewards or obtain immediate rewards) and one
      of two types of instruction (indirect priming using stories or explicit verbal
      instructions). Children were more likely to make goal-congruent choices as a
      result of indirect priming, but there was no effect of explicit instruction,
      suggesting that indirect approaches to changing young children's behavior may be
      more effective than direct approaches under some circumstances. These results
      have implications for understanding the dynamic interplay between bottom-up and
      top-down influences on self-regulation early in development.

PMID- 21884311
TI  - Rapid reacquisition of native phoneme contrasts after disuse: you do not always
      lose what you do not use.
AB  - Infants attune to their birth language during the second half of infancy.
      However, internationally adopted children are often uniquely required to attune
      to their birth language, and then reattune to their adoptive language. Children
      who were adopted from India into America at ages 6-60 months (N = 8) and had
      minimal further exposure to their birth languages were compared to age-matched
      American non-adopted controls. Without training, neither group could discriminate
      a phonemic contrast that occurs in their birth language but not in English.
      However, after training on the contrast, the adopted group (N = 8) improved
      significantly and discriminated the contrast more accurately than their non
      adopted peers. While English had explicitly replaced the birth language of the
      adopted sample, traces of early exposure conferred privileges on subsequent
      learning. These findings are consistent with behavioral and neurophysiological
      data from animals that have identified some of the mechanisms underlying such a
      'retention without further use' phenomenon.

PMID- 21884312
TI  - The dynamics of development on the Dimensional Change Card Sorting task.
AB  - A widely used paradigm to study cognitive flexibility in preschoolers is the
      Dimensional Change Card Sorting (DCCS) task. The developmental dynamics of DCCS
      performance was studied in a cross-sectional design (N = 93, 3 to 5 years of age)
      using a computerized version of the standard DCCS task. A model-based analysis of
      the data showed that development on the DCCS task is best described as a
      discontinuous change in performance on the post-switch phase of the task. In
      addition to a perseveration group and a switch group, a transitional group that
      showed shifts between perseverating and switching during the post-switch trials
      could be distinguished. Computational models of performance and development on
      the DCCS task cannot, in their current forms, explain these results. We discuss
      how a catastrophe model of the developmental changes in task performance could be
      used to generate specific hypotheses about the variables that control development
      of DCCS performance.

PMID- 21884313
TI  - Infants avoid 'labouring in vain' by attending more to learnable than unlearnable
      linguistic patterns.
AB  - Every environment contains infinite potential features and correlations among
      features, or patterns. Detecting valid and learnable patterns in one environment
      is beneficial for learners because doing so lends predictability to new
      environments where the same or analogous patterns recur. However, some apparent
      correlations among features reflect spurious patterns, and attempting to learn
      the latter costs time and resources with no advantage to the learner. Thus, an
      efficient learner in a complex environment needs to devote more attention to
      input that reflects a real and learnable pattern than to input that reflects a
      spurious or ultimately unlearnable pattern. However, in order to achieve such
      efficiency in the absence of external feedback, learners need to have an implicit
      metric of their own learning progress. Do human infants have such a metric? Data
      from two experiments demonstrate that 17-month-olds attend longer to learnable
      vs. unlearnable linguistic grammars, taking more trials to habituate and more
      overall time to habituate for grammars in which a valid generalization over input
      stimuli can be made. These data provide the first evidence that infants have an
      implicit metric of their own learning progress and preferentially direct their
      attention to learnable aspects of their environment.

PMID- 21884314
TI  - Toddlers with Autism Spectrum Disorder are more successful at visual search than
      typically developing toddlers.
AB  - Plaisted, O'Riordan and colleagues (Plaisted, O'Riordan & Baron-Cohen, 1998;
      O'Riordan, 2004) showed that school-age children and adults with Autism Spectrum
      Disorder (ASD) are faster at finding targets in certain types of visual search
      tasks than typical controls. Currently though, there is very little known about
      the visual search skills of very young children (1-3-year-olds) - either
      typically developing or with ASD. We used an eye-tracker to measure looking
      behavior, providing fine-grained measures of visual search in 2.5-year-old
      toddlers with and without ASD (this representing the age by which many children
      may first receive a diagnosis of ASD). Importantly, our paradigm required no
      verbal instructions or feedback, making the task appropriate for toddlers who are
      pre- or nonverbal. We found that toddlers with ASD were more successful at
      finding the target than typically developing, age-matched controls. Further, our
      paradigm allowed us to estimate the number of items scrutinized per trial,
      revealing that for large set size conjunctive search, toddlers with ASD
      scrutinized as many as twice the number of items as typically developing
      toddlers, in the same amount of time.

PMID- 21884316
TI  - Infant ability to tell voices apart rests on language experience.
AB  - A visual fixation study tested whether 7-month-olds can discriminate between
      different talkers. The infants were first habituated to talkers producing
      sentences in either a familiar or unfamiliar language, then heard test sentences
      from previously unheard speakers, either in the language used for habituation, or
      in another language. When the language at test mismatched that in habituation,
      infants always noticed the change. When language remained constant and only
      talker altered, however, infants detected the change only if the language was the
      native tongue. Adult listeners with a different native tongue from the infants
      did not reproduce the discriminability patterns shown by the infants, and infants
      detected neither voice nor language changes in reversed speech; both these
      results argue against explanation of the native-language voice discrimination in
      terms of acoustic properties of the stimuli. The ability to identify talkers is,
      like many other perceptual abilities, strongly influenced by early life
      experience.

PMID- 21884315
TI  - How does a child solve 7 + 8? Decoding brain activity patterns associated with
      counting and retrieval strategies.
AB  - Cognitive development and learning are characterized by diminished reliance on
      effortful procedures and increased use of memory-based problem solving. Here we
      identify the neural correlates of this strategy shift in 7-9-year-old children at
      an important developmental period for arithmetic skill acquisition. Univariate
      and multivariate approaches were used to contrast brain responses between two
      groups of children who relied primarily on either retrieval or procedural
      counting strategies. Children who used retrieval strategies showed greater
      responses in the left ventrolateral prefrontal cortex; notably, this was the only
      brain region which showed univariate differences in signal intensity between the
      two groups. In contrast, multivariate analysis revealed distinct multivoxel
      activity patterns in bilateral hippocampus, posterior parietal cortex and left
      ventrolateral prefrontal cortex regions between the two groups. These results
      demonstrate that retrieval and counting strategies during early learning are
      characterized by distinct patterns of activity in a distributed network of brain
      regions involved in arithmetic problem solving and controlled retrieval of
      arithmetic facts. Our findings suggest that the reorganization and refinement of
      neural activity patterns in multiple brain regions plays a dominant role in the
      transition to memory-based arithmetic problem solving. Our findings further
      demonstrate how multivariate approaches can provide novel insights into fine
      scale developmental changes in the brain. More generally, our study illustrates
      how brain imaging and developmental research can be integrated to investigate
      fundamental aspects of neurocognitive development.

PMID- 21884317
TI  - The developmental roots of fairness: infants' reactions to equal and unequal
      distributions of resources.
AB  - The problem of how to distribute available resources among members of a group is
      a central aspect of social life. Adults react negatively to inequitable
      distributions and several studies have reported negative reactions to inequity
      also in non-human primates and dogs. We report two experiments on infants'
      reactions to equal and unequal distributions. In two experiments, infants'
      looking times and manual choices provide, for the first time, converging evidence
      suggesting that infants aged 12 to 18 months (mean age 16 months) attend to the
      outcomes of distributive actions to evaluate agents' actions and to reason about
      agents' dispositions. The results provide support for recent theoretical
      proposals on the developmental roots of social evaluation skills and a sense of
      fairness.

PMID- 21884318
TI  - Some types of parent number talk count more than others: relations between
      parents' input and children's cardinal-number knowledge.
AB  - Before they enter preschool, children vary greatly in their numerical and
      mathematical knowledge, and this knowledge predicts their achievement throughout
      elementary school (e.g. Duncan et al., 2007; Ginsburg & Russell, 1981).
      Therefore, it is critical that we look to the home environment for parental
      inputs that may lead to these early variations. Recent work has shown that the
      amount of number talk that parents engage in with their children is robustly
      related to a critical aspect of mathematical development - cardinal-number
      knowledge (e.g. knowing that the word 'three' refers to sets of three entities;
      Levine, Suriyakham, Rowe, Huttenlocher & Gunderson, 2010). The present study
      characterizes the different types of number talk that parents produce and
      investigates which types are most predictive of children's later cardinal-number
      knowledge. We find that parents' number talk involving counting or labeling sets
      of present, visible objects is related to children's later cardinal-number
      knowledge, whereas other types of parent number talk are not. In addition, number
      talk that refers to large sets of present objects (i.e. sets of size 4 to 10 that
      fall outside children's ability to track individual objects) is more robustly
      predictive of children's later cardinal-number knowledge than talk about smaller
      sets. The relation between parents' number talk about large sets of present
      objects and children's cardinal-number knowledge remains significant even when
      controlling for factors such as parents' socioeconomic status and other measures
      of parents' number and non-number talk.

PMID- 21884319
TI  - The contribution of visual and vestibular information to spatial orientation by 6
      to 14-month-old infants and adults.
AB  - Although there is much research on infants' ability to orient in space, little is
      known regarding the information they use to do so. This research uses a rotating
      room to evaluate the relative contribution of visual and vestibular information
      to location of a target following bodily rotation. Adults responded precisely on
      the basis of visual flow information. Seven-month-olds responded mostly on the
      basis of visual flow, whereas 9-month-olds responded mostly on the basis of
      vestibular information, and 12-month-olds responded mostly on the basis of visual
      information. Unlike adults, infants of all ages showed partial influence by both
      modalities. Additionally, 7-month-olds were capable of using vestibular
      information when there was no visual information for movement or stability, and 9
      month-olds still relied on vestibular information when visual information was
      enhanced. These results are discussed in the context of neuroscientific evidence
      regarding visual-vestibular interaction, and in relation to possible changes in
      reliance on visual and vestibular information following acquisition of
      locomotion.

PMID- 21884321
TI  - The association between infants' self-regulatory behavior and MAOA gene
      polymorphism.
AB  - Self-regulatory behavior in early childhood is an important characteristic that
      has considerable implications for the development of adaptive and maladaptive
      functioning. The present study investigated the relations between a functional
      polymorphism in the upstream region of monoamine oxidase A gene (MAOA) and self
      regulatory behavior in a sample of Chinese infants at 6 months of age. Self
      regulation was assessed by observing infants' behavior of orienting visual
      attention away from a threatening event in the laboratory situation. The results
      indicated that regulatory behavior was associated with the functional MAOA gene
      polymorphism in girls, but not boys. Girls with 4/4 genotypes displayed
      significantly higher regulation than girls with 3/3 and 3/4 genotypes. The
      present study provided evidence for gender differences on the role of MAOA gene
      polymorphism in socioemotional functioning in the early years.

PMID- 21884320
TI  - The effects of an afterschool physical activity program on working memory in
      preadolescent children.
AB  - The present study examined the effects of a 9-month randomized control physical
      activity intervention aimed at improving cardiorespiratory fitness on changes in
      working memory performance in preadolescent children relative to a waitlist
      control group. Participants performed a modified Sternberg task, which
      manipulated working memory demands based on encoding set sizes, while task
      performance and the contingent negative variation (CNV) event-related brain
      potential were measured. Analyses revealed that the physical activity
      intervention led to increases in cardiorespiratory fitness and improved Sternberg
      task performance. Further, the beneficial effects of the physical activity
      intervention were greater for a task condition requiring greater working memory
      demands. In addition, the intervention group exhibited larger initial CNV at the
      frontal electrode site, relative to the waitlist group at post-test; an effect
      not observed during the pre-test. These results indicate that increases in
      cardiorespiratory fitness are associated with improvements in the cognitive
      control of working memory in preadolescent children.

PMID- 21884322
TI  - Age differences in visual working memory capacity: not based on encoding
      limitations.
AB  - Why does visual working memory performance increase with age in childhood? One
      recent study (Cowan et al., 2010b) ruled out the possibility that the basic cause
      is a tendency in young children to clutter working memory with less-relevant
      items (within a concurrent array, colored items presented in one of two shapes).
      The age differences in memory performance, however, theoretically could result
      from inadequate encoding of the briefly presented array items by younger
      children. We replicated the key part of the procedure in children 6-8 and 11-13
      years old and college students (total N = 90), but with a much slower, sequential
      presentation of the items to ensure adequate encoding. We also required verbal
      responses during encoding to encourage or discourage labeling of item
      information. Although verbal labeling affected performance, age differences
      persisted across labeling conditions, further supporting the existence of a basic
      growth in capacity.

PMID- 21884324
TI  - Susceptibility to the flash-beep illusion is increased in children compared to
      adults.
AB  - Audio-visual integration was studied in children aged 8-17 (N = 30) and adults (N
      = 22) using the 'flash-beep illusion' paradigm, where the presentation of two
      beeps causes a single flash to be perceived as two flashes (fission illusion),
      and a single beep causes two flashes to be perceived as one flash (fusion
      illusion). Children reported significantly more fission illusions than adults,
      indicating that auditory and visual information was integrated more often, and
      less selectively, than in adults. Within either group, illusion reports did not
      correlate with either age or motor coordination measures. The current results
      show that the form of multisensory integration indexed by the illusion is slow to
      mature in normally developing children.

PMID- 21884323
TI  - Neural correlates of coherent and biological motion perception in autism.
AB  - Recent evidence suggests those with autism may be generally impaired in visual
      motion perception. To examine this, we investigated both coherent and biological
      motion processing in adolescents with autism employing both psychophysical and
      fMRI methods. Those with autism performed as well as matched controls during
      coherent motion perception but had significantly higher thresholds for biological
      motion perception. The autism group showed reduced posterior Superior Temporal
      Sulcus (pSTS), parietal and frontal activity during a biological motion task
      while showing similar levels of activity in MT+/V5 during both coherent and
      biological motion trials. Activity in MT+/V5 was predictive of individual
      coherent motion thresholds in both groups. Activity in dorsolateral prefrontal
      cortex (DLPFC) and pSTS was predictive of biological motion thresholds in control
      participants but not in those with autism. Notably, however, activity in DLPFC
      was negatively related to autism symptom severity. These results suggest that
      impairments in higher-order social or attentional networks may underlie visual
      motion deficits observed in autism.

PMID- 21884325
TI  - On-line statistical segmentation of a non-speech auditory stream in neonates as
      demonstrated by event-related brain potentials.
AB  - The ability to statistically segment a continuous auditory stream is one of the
      most important preparations for initiating language learning. Such ability is
      available to human infants at 8 months of age, as shown by a behavioral
      measurement. However, behavioral study alone cannot determine how early this
      ability is available. A recent study using measurements of event-related
      potential (ERP) revealed that neonates are able to detect statistical boundaries
      within auditory streams of speech syllables. Extending this line of research will
      allow us to better understand the cognitive preparation for language acquisition
      that is available to neonates. The aim of the present study was to examine the
      domain-generality of such statistical segmentation. Neonates were presented with
      nonlinguistic tone sequences composed of four tritone units, each consisting of
      three semitones extracted from one octave, for two 5-minute sessions. Only the
      first tone of each unit evoked a significant positivity in the frontal area
      during the second session, but not in the first session. This result suggests
      that the general ability to distinguish units in an auditory stream by
      statistical information is activated at birth and is probably innately prepared
      in humans.

PMID- 21884326
TI  - Age-related differences in brain electrical activity during extended continuous
      face recognition in younger children, older children and adults.
AB  - To examine the development of recognition memory in primary-school children, 36
      healthy younger children (8-9 years old) and 36 healthy older children (11-12
      years old) participated in an ERP study with an extended continuous face
      recognition task (Study 1). Each face of a series of 30 faces was shown randomly
      six times interspersed with distracter faces. The children were required to make
      old vs. new decisions. Older children responded faster than younger children, but
      younger children exhibited a steeper decrease in latencies across the five
      repetitions. Older children exhibited better accuracy for new faces, but there
      were no age differences in recognition accuracy for repeated faces. For the N2,
      N400 and late positive complex (LPC), we analyzed the old/new effects (repetition
      1 vs. new presentation) and the extended repetition effects (repetitions 1
      through 5). Compared to older children, younger children exhibited larger
      frontocentral N2 and N400 old/new effects. For extended face repetitions,
      negativity of the N2 and N400 decreased in a linear fashion in both age groups.
      For the LPC, an ERP component thought to reflect recollection, no significant
      old/new or extended repetition effects were found. Employing the same face
      recognition paradigm in 20 adults (Study 2), we found a significant N400 old/new
      effect at lateral frontal sites and a significant LPC repetition effect at
      parietal sites, with LPC amplitudes increasing linearly with the number of
      repetitions. This study clearly demonstrates differential developmental courses
      for the N400 and LPC pertaining to recognition memory for faces. It is concluded
      that face recognition in children is mediated by early and probably more
      automatic than conscious recognition processes. In adults, the LPC extended
      repetition effect indicates that adult face recognition memory is related to a
      conscious and graded recollection process rather than to an automatic recognition
      process.

PMID- 21884327
TI  - Does adolescent risk taking imply weak executive function? A prospective study of
      relations between working memory performance, impulsivity, and risk taking in
      early adolescence.
AB  - Studies of brain development suggest that the increase in risk taking observed
      during adolescence may be due to insufficient prefrontal executive function
      compared to a more rapidly developing subcortical motivation system. We examined
      executive function as assessed by working memory ability in a community sample of
      youth (n = 387, ages 10 to 12 at baseline) in three annual assessments to
      determine its relation to two forms of impulsivity (sensation seeking and acting
      without thinking) and a wide range of risk and externalizing behavior. Using
      structural equation modeling, we tested a model in which differential activation
      of the dorsal and ventral striatum produces imbalance in the function of these
      brain regions. For youth high in sensation seeking, both regions were predicted
      to develop with age. However, for youth high in the tendency to act without
      thinking, the ventral striatum was expected to dominate. The model predicted that
      working memory ability would exhibit (1) early weakness in youth high in acting
      without thinking but (2) growing strength in those high in sensation seeking. In
      addition, it predicted that (3) acting without thinking would be more strongly
      related to risk and externalizing behavior than sensation seeking. Finally, it
      predicted that (4) controlling for acting without thinking, sensation seeking
      would predict later increases in risky and externalizing behavior. All four of
      these predictions were confirmed. The results indicate that the rise in sensation
      seeking that occurs during adolescence is not accompanied by a deficit in
      executive function and therefore requires different intervention strategies from
      those for youth whose impulsivity is characterized by early signs of acting
      without thinking.

PMID- 21884328
TI  - One-month-old human infants learn about the social world while they sleep.
AB  - Although infants display preferences for social stimuli early in their lives, we
      know relatively little about the mechanisms of infant learning about the social
      world. In the current set of studies, 1-month-old infants underwent an adapted
      eyeblink conditioning paradigm to examine learning to both 'social' and non
      social cues. While infants were asleep, they were presented with either a
      'social' stimulus (a female voice) or one of two non-social stimuli (tone or
      backward voice) followed by an airpuff presented to the eyelid. Infants in the
      experimental groups displayed increased learning across trials, regardless of
      stimulus type. However, infants conditioned to the 'social' stimulus showed
      increased learning compared to infants conditioned to either of the non-social
      stimuli. These results suggest a mechanism by which learning about the social
      world occurs early in life and the power of ecologically valid cues in
      facilitating that learning.

PMID- 21884329
TI  - Symbolic play connects to language through visual object recognition.
AB  - Object substitutions in play (e.g. using a box as a car) are strongly linked to
      language learning and their absence is a diagnostic marker of language delay.
      Classic accounts posit a symbolic function that underlies both words and object
      substitutions. Here we show that object substitutions depend on developmental
      changes in visual object recognition: 18- to 30-month old children (n = 63)
      substitute objects in play after they have developed the adult-like ability to
      recognize common objects from sparse models of their geometric structure. These
      developmental changes in object recognition are a better predictor of object
      substitutions than language or age. A developmental pathway connecting visual
      object recognition, object name learning, and symbolic play is proposed in which
      object substitutions are like the canary in the coal mine: they are not causally
      related to language delay, but their absence is an easily detected signal of a
      problem in language acquisition.

PMID- 21884330
TI  - Micro-analysis of infant looking in a naturalistic social setting: insights from
      biologically based models of attention.
AB  - A current theory of attention posits that several micro-indices of attentional
      vigilance are dependent on activation of the locus coeruleus, a brainstem nucleus
      that regulates cortical norepinephrine activity (Aston-Jones et al., 1999). This
      theory may account for many findings in the infant literature, while highlighting
      important new areas for research and theory on infant attention. We examined the
      visual behaviors of n = 16 infants (6-7 months) while they attended to multiple
      spatially distributed targets in a naturalistic environment. We coded four
      measures of attentional vigilance, adapted from studies of norepinergic
      modulation of animal attention: rate of fixations, duration of fixations, latency
      to reorientation, and target 'hits'. These measures showed a high degree of
      coherence in individual infants, in parallel with findings from animal studies.
      Results also suggest that less vigilant infants showed greater habituation to the
      trial structure and more attentiveness to less salient stimuli during periods of
      high attentional competition. This pattern of results is predicted by the Aston
      Jones model of attention, but could not be explained by the standard information
      processing model.

PMID- 21884331
TI  - Modeling a cascade of effects: the role of speed and executive functioning in
      preterm/full-term differences in academic achievement.
AB  - This study identified deficits in executive functioning in pre-adolescent
      preterms and modeled their role, along with processing speed, in explaining
      preterm/full-term differences in reading and mathematics. Preterms (< 1750 g)
      showed deficits at 11 years on a battery of tasks tapping the three basic
      executive functions identified by Miyake - updating/working memory, inhibition,
      and shifting. Confirmatory factor analysis showed that these executive functions,
      though correlated, were distinct from one another and from processing speed,
      which later proved to account for much of the intercorrelation among executive
      functions. In the best-fitting structural equation model, the negative effects of
      prematurity on achievement were completely mediated by the three executive
      functions and speed in a cascade of effects: prematurity -> slower processing
      speed -> poorer executive functioning (working memory) -> lower achievement in
      math and reading.

PMID- 21884332
TI  - Developing cultural differences in face processing.
AB  - Perception and eye movements are affected by culture. Adults from Eastern
      societies (e.g. China) display a disposition to process information holistically,
      whereas individuals from Western societies (e.g. Britain) process information
      analytically. Recently, this pattern of cultural differences has been extended to
      face processing. Adults from Eastern cultures fixate centrally towards the nose
      when learning and recognizing faces, whereas adults from Western societies spread
      fixations across the eye and mouth regions. Although light has been shed on how
      adults can fixate different areas yet achieve comparable recognition accuracy,
      the reason why such divergent strategies exist is less certain. Although some
      argue that culture shapes strategies across development, little direct evidence
      exists to support this claim. Additionally, it has long been claimed that face
      recognition in early childhood is largely reliant upon external rather than
      internal face features, yet recent studies have challenged this theory. To
      address these issues, we tested children aged 7-12 years of age from the UK and
      China with an old/new face recognition paradigm while simultaneously recording
      their eye movements. Both populations displayed patterns of fixations that were
      consistent with adults from their respective cultural groups, which
      'strengthened' across development as qualified by a pattern classifier analysis.
      Altogether, these observations suggest that cultural forces may indeed be
      responsible for shaping eye movements from early childhood. Furthermore,
      fixations made by both cultural groups almost exclusively landed on internal face
      regions, suggesting that these features, and not external features, are
      universally used to achieve face recognition in childhood.

PMID- 21884333
TI  - Changing patterns of neuropsychological functioning in children living at high
      altitude above and below 4000 m: a report from the Bolivian Children Living at
      Altitude (BoCLA) study.
AB  - The brain is highly sensitive to environmental hypoxia. Little is known, however,
      about the neuropsychological effects of high altitude residence in the developing
      brain. We recently described only minor changes in processing speed in native
      Bolivian children and adolescents living at approximately 3700 m. However,
      evidence for loss of cerebral autoregulation above this altitude (4000 m)
      suggests a potential threshold of hypoxia severity over which neuropsychological
      functioning may be compromised. We conducted physiological and neuropsychological
      assessments in 62 Bolivian children and adolescents living at La Paz (~3700 m)
      and El Alto (~4100 m) in order to address this issue. Groups were equivalent in
      terms of age, gender, social class, schooling, parental education and genetic
      admixture. Apart from percentage of hemoglobin saturated with oxygen in arterial
      blood (%SpO(2)), participants did not differ in their basal cardiac and
      cerebrovascular performance as explored by heart rate, mean arterial pressure,
      end-tidal carbon dioxide, and cerebral blood flow velocity at the basilar,
      anterior, middle and posterior cerebral arteries. A comprehensive
      neuropsychological assessment was administered, including tests of executive
      functions, attention, memory and psychomotor performance. Participants living at
      extreme altitude showed lower levels of performance in all executive tests (Cohen
      effect size = -0.91), whereas all other domains remained unaffected by altitude
      of residence. These results are compatible with earlier physiological evidence of
      a transitional zone for cerebral autoregulation at an altitude of 4000 m. We now
      show that above this threshold, the developing brain is apparently increasingly
      vulnerable to neuropsychological deficit.

PMID- 21884334
TI  - The powers of noise-fitting: reply to Barth and Paladino.
AB  - Barth and Paladino (2011) argue that changes in numerical representations are
      better modeled by a power function whose exponent gradually rises to 1 than as a
      shift from a logarithmic to a linear representation of numerical magnitude.
      However, the fit of the power function to number line estimation data may simply
      stem from fitting noise generated by averaging over changing proportions of
      logarithmic and linear estimation patterns. To evaluate this possibility, we used
      conventional model fitting techniques with individual as well as group average
      data; simulations that varied the proportion of data generated by different
      functions; comparisons of alternative models' prediction of new data; and
      microgenetic analyses of rates of change in experiments on children's learning.
      Both new data and individual participants' data were predicted less accurately by
      power functions than by logarithmic and linear functions. In microgenetic
      studies, changes in the best fitting power function's exponent occurred abruptly,
      a finding inconsistent with Barth and Paladino's interpretation that development
      of numerical representations reflects a gradual shift in the shape of the power
      function. Overall, the data support the view that change in this area entails
      transitions from logarithmic to linear representations of numerical magnitude.

PMID- 21884336
TI  - Interactions between statistical and semantic information in infant language
      development.
AB  - Infants can use statistical regularities to form rudimentary word categories
      (e.g. noun, verb), and to learn the meanings common to words from those
      categories. Using an artificial language methodology, we probed the mechanisms by
      which two types of statistical cues (distributional and phonological
      regularities) affect word learning. Because linking distributional cues vs.
      phonological information to semantics make different computational demands on
      learners, we also tested whether their use is related to language proficiency. We
      found that 22-month-old infants with smaller vocabularies generalized using
      phonological cues; however, infants with larger vocabularies showed the opposite
      pattern of results, generalizing based on distributional cues. These findings
      suggest that both phonological and distributional cues marking word categories
      promote early word learning. Moreover, while correlations between these cues are
      important to forming word categories, we found infants' weighting of these cues
      in subsequent word-learning tasks changes over the course of early language
      development.

PMID- 21884337
TI  - The development of a greeting signal in wild chimpanzees.
AB  - Adult chimpanzees produce a unique vocal signal, the pant-grunt, when
      encountering higher-ranking group members. The behaviour is typically directed to
      a specific receiver and has thus been interpreted as a 'greeting' signal. The
      alpha male obtains a large share of these calls, followed by the other adult
      males of the group. In this study, we describe the development of pant-grunting
      behaviour from the first grunt-like calls of newborn babies to the fully
      developed pant-grunts in adults. Although babies produce grunts from very early
      on, they are not directed to others until about 2 months of age. Subsequently,
      socially directed grunting steadily increases in frequency to peak around 7
      months of age, but then decreases again to reach a nadir in older infants and
      juveniles, while the specificity in use increases. During adolescence, grunt
      production increases again with grunts given most frequently to socially relevant
      individuals. As young chimpanzees are closely affiliated to their mothers for the
      first decade of their lives, we also compared the grunting patterns of mothers
      and their offspring, which revealed some influences in pant-grunt production. In
      conclusion, the acquisition of pant-grunting behaviour in chimpanzees is a long
      lasting process with distinct developmental phases in which social influences by
      the mother and other group members are likely to play a role.

PMID- 21884338
TI  - Object individuation in 3-day-old chicks: use of property and spatiotemporal
      information.
AB  - Object individuation was investigated in newborn domestic chicks. Chicks'
      spontaneous tendency to approach the larger group of familiar objects was
      exploited in a series of five experiments. In the first experiment newborn chicks
      were reared for 3 days with objects differing in either colour, shape or size. At
      test, each chick was presented with two groups of events: two objects differing
      in one property vs. two presentations of the same object. In both cases, all
      objects involved in the same group of events were sequentially presented and
      eventually concealed in a different spatial location, and the number of events
      taking place at each location was equalized. Chicks spontaneously approached the
      two different objects rather than the single object seen twice. Chicks did not
      just prefer the more varied set as they did not choose it when the two elements
      of each group of events were simultaneously presented (Experiment 2). Chicks
      succeeded when two different objects simultaneously presented were confronted
      with three identical ones simultaneously presented (Experiment 3), though they
      failed with sequential presentation of two different objects vs. one object
      presented three times if they had been familiarized with up to three identical
      objects (Experiment 4). Chicks instead succeeded if they had been familiarized
      with objects that were all different from one another (Experiment 5). These young
      birds thus proved able to use property and spatiotemporal information for object
      individuation.

PMID- 21884340
TI  - Diagnostic criteria of acute liver failure: A report by the Intractable Hepato
      Biliary Diseases Study Group of Japan.
AB  - The diagnostic criteria of fulminant hepatitis in Japan are different from those
      of acute liver failure in Europe and the United States, both in regard to the
      histological features in the liver and the cutoff values of the prothrombin time.
      Thus, the Intractable Hepato-Biliary Disease Study Group established novel
      diagnostic criteria for "acute liver failure" in Japan based on the demographic
      and clinical features of the patients. Patients showing prothrombin time values
      of 40% or less of the standardized values or international normalized ratios of
      1.5 or more caused by severe liver damage within 8 weeks of onset of the symptoms
      are diagnosed as having "acute liver failure", where the liver function prior to
      the current onset of liver damage is estimated to be normal. Acute liver failure
      is classified into "acute liver failure without hepatic coma" and "acute liver
      failure with hepatic coma," depending on the severity of the hepatic
      encephalopathy; the latter is further classified into two types, the "acute type"
      and the "subacute type", in which grade II or more severe hepatic coma develops
      within 10 days and between 11 and 56 days, respectively, after the onset of
      disease symptoms. Patients without histological findings of hepatitis, such as
      those with liver damage caused by drug toxicity, circulatory disturbance or
      metabolic disease, are also included in the disease entity of "acute liver
      failure", while acute-on-chronic liver injuries, such as liver injury caused by
      alcohol, are excluded. A nationwide survey of "acute liver failure" in Japan
      based on the novel criteria is proposed.

PMID- 21884339
TI  - Correlated longitudinal changes across linguistic, achievement, and psychomotor
      domains in early childhood: evidence for a global dimension of development.
AB  - An important question within developmental psychology concerns the extent to
      which the maturational gains that children make across multiple diverse domains
      of functioning can be attributed to global (domain-general) developmental
      processes. The present study investigated this question by examining the extent
      to which individual differences in change across children's development in five
      different domains are correlated. Multivariate growth-curve models were fit to
      longitudinal data on linguistic, mathematics, reading, gross motor, and fine
      motor skills in 8950 children ranging in age from 44 to 86 months (3.7 years to
      7.2 years). All five rates of change were positively intercorrelated. A common
      factor accounted for 42% of the individual differences in change. These results
      suggest that a global dimension underlies substantial proportions of cognitive
      and psychomotor development.

PMID- 21884341
TI  - Early detection of interstitial pneumonia by monitoring KL-6 in a chronic
      hepatitis C patient undergoing pegylated interferon and ribavirin therapy.
AB  - A 58-year-old woman with chronic hepatitis C developed interstitial pneumonia
      (IP) while undergoing pegylated interferon (PEG IFN)-alpha-2a and ribavirin (RBV)
      therapy. Serum levels of sialylated carbohydrate antigen KL-6 (KL-6), a known
      marker of disease activity in fibrosing lung disorders, had been regularly
      measured once a month for early detection of IP, and had begun rising noticeably
      from 12 weeks to 540 U/mL at 33 weeks of treatment. On examination, remarkable
      fine crackles were detected by dorsal auscultation and bilateral ground-glass
      opacities and reticular shadows were depicted by computed tomography. The patient
      successfully recovered from her early-stage pneumonia by immediate
      discontinuation of therapy, which indicates that regular monitoring of serum KL-6
      may be effective for avoidance of IP progression induced by PEG IFN and RBV
      therapy.

PMID- 21884342
TI  - Late-onset graft-versus-host disease after pediatric living-related liver
      transplantation for Langerhans cell histiocytosis.
AB  - GVHD is the most common and well-known cause of morbidity and mortality following
      allogeneic BM transplantation. The GVHD following OLT is an uncommon complication
      but has a high mortality and poses a major diagnostic and therapeutic challenge.
      We herein discussed a 12-month-old girl with multi-system LCH, who developed end
      stage liver disease despite intensive chemotherapy. She underwent ABO-compatible
      liver transplantation at 28 months while in remission from LCH. The donor was her
      26-yr-old father. Post-operative course was uneventful. The GVHD manifested with
      skin rash and BM suppression on post-transplant day 94 and confirmed by both
      microchimerism and skin biopsy. Prednisolone, basiliximab, and ATG were
      administered immediately but the bone marrow suppression was not improved and the
      patient died because of Candida sepsis at six-month post-transplant. GVHD after
      OLT should be keep in mind in patients with rash and BM suppression after liver
      transplantation. In LDLT, a patient who carries risk factors should investigated
      for optimal HLA matching.

PMID- 21884343
TI  - High urgency liver transplantation in ornithine transcarbamylase deficiency
      presenting with acute liver failure.
AB  - OTCD can present with ALF at any age. Under adequate therapy symptoms resolve
      quickly. We report a three-yr-old girl with the manifestation of an OTCD as ALF.
      Despite adequate pharmacotherapy and protein restriction, the patient
      deteriorated and developed hepatic encephalopathy. A high urgency liver
      transplantation was performed and the patient recovered completely. We conclude
      that in patients with ALF urea cycle defects in general and OTCD in particular
      should be considered as differential diagnosis. Patients should be managed in a
      center that has the capacity for an emergency liver transplantation.

PMID- 21884344
TI  - Proteasome inhibitor therapy for antibody-mediated rejection.
AB  - AMR is being recognized with increasing efficiency, but continues to present a
      significant threat to renal allograft survival. Traditional therapies for AMR
      (IVIG, plasmapheresis, rituximab, and antilymphocyte preparations) in general
      have provided inconsistent results and do not deplete the source of antibody
      production, viz., the mature plasma cell. Recently, the first plasma cell
      targeted therapy in humans has been developed using bortezomib (a first in class
      PI) for AMR treatment in kidney transplant recipients. Initial experience with
      bortezomib involved treatment of refractory AMR. Subsequently, the efficacy of
      bortezomib in primary therapy for AMR was demonstrated. In a multicenter
      collaborative effort, the initial results with bortezomib in AMR have been
      confirmed and expanded to pediatric and adult heart transplant recipients. More
      recently, results from a prospective, staged desensitization trial has shown that
      bortezomib alone can substantially reduce anti-HLA antibody levels. These results
      demonstrate the significant potential of proteasome inhibition in addressing
      humoral barriers. However, the major advantage of proteasome inhibition lies in
      the numerous potential strategies for achieving synergy.

PMID- 21884345
TI  - Linear growth in pediatric renal transplant recipients receiving sirolimus.
AB  - SRL is a potent macrolide immunosuppressive agent that can be used as maintenance
      therapy for prevention of rejection and avoidance of CNI nephrotoxicity. However,
      animal studies indicate that SRL may inhibit skeletal and muscle growth. We
      analyzed linear growth in 25 children, age 1-15 yr old, maintained on SRL to
      determine whether SRL is detrimental to linear growth. Height z-scores at
      baseline were compared with those at 24 months. We also compared linear growth in
      children receiving SRL to patients maintained on TAC. Height z-scores over 24
      months did not significantly change in the SRL group as a whole. Z-scores
      improved in 13 of 25 patients (52%). Children with improved z-scores were
      significantly younger than patents who did not display improved growth: 6 +/- 5
      yr vs. 11 +/- 4 yr (p < 0.05). Height z-scores in SRL and TAC-based patients were
      no different initially and at 24 months, and a similar number of patients in each
      group displayed improved height scores. Height z-scores improved in 52% of
      patients on SRL and occurred predominantly in younger patients for the initial 24
      months of treatment. Linear growth in SRL patients was also similar to the
      results in TAC-based patients. Therefore, our data did not identify a significant
      adverse effect of SRL on growth.

PMID- 21884346
TI  - Prognostic significance of recurrent grade 1B rejection in the first year after
      pediatric cardiac transplantation: a case for reinstatement of the 1B rejection
      grade.
AB  - The 2005 ISHLT rejection grading system merged grades 1A, 1B, and 2 into a single
      grade (1R) assuming equivalent prognostic significance. We hypothesized that
      recurrent 1B ACR is associated with adverse outcomes. Data on all heart
      transplant recipients at our center from 1990 to 2007 were reviewed. Patients
      were excluded if they had more than one grade >= 3A/2R biopsy in the first six wk
      or any grade >= 3A/2R biopsies during the first year thereafter. Patients with >=
      2 grade 1B biopsies from six wk to one yr were classified as "recurrent 1B."
      Outcomes were freedom from late (greater than one yr) ACR (grade >= 3A/2R), CAD,
      retransplantation/death, and a composite end-point. Sixty-two patients (53 non
      recurrent 1B, nine recurrent 1B) met inclusion criteria. In univariate analyses,
      recurrent 1B status was associated with decreased freedom from late ACR (p <
      0.001), CAD (p = 0.004), and the composite outcome (p < 0.001). There was no
      difference in freedom from retransplantation/death (p = 0.48). After controlling
      for demographic differences between the groups, recurrent 1B status was
      independently associated with late ACR (HR 5.90; p = 0.002) and the composite
      outcome (HR 4.52; p = 0.002). These data suggest that further study of the impact
      of removal of the 1B classification from the ISHLT grading scheme is warranted.

PMID- 21884347
TI  - The role of interleukin-6, endothelins, and apoptotic genes in small bowel
      transplantation, in a swine model of ischemia and reperfusion injury.
AB  - IRI is closely related to sepsis in ITx setting. Complete understanding of the
      mechanisms involved in IRI development may improve outcomes. Ortothopic ITx
      without immunosuppression was performed in order to characterize IRI-associated
      mucosal damage. Twenty pigs underwent ITx. Two groups were assigned to different
      CI times: G1: 90 min and, G2: 180 min. Euro-Collins was used as preservation
      solution. Jejunal fragments were collected at donor laparotomy, 30 min, and 3
      days after reperfusion. IRI assessment involved: histopathologic analysis,
      quantification of MPO-positive cells through immunohistochemical studies,
      quantification of epithelial apoptotic cells using TUNEL staining, and
      quantification of IL-6, ET-1, Bak, and Bcl-XL genes expression by RT-PCR.
      Neutrophilic infiltration increased in a similar fashion in both groups, but
      lasted longer in G2. Apoptosis detected by TUNEL staining increased and anti
      apoptotic gene Bcl-XL expression decreased significantly in G1, 3 days after
      surgery. Endothelin-1 and IL-6 genes expression increased 30 min after the
      procedure and returned to baseline 3 days after surgery. In conclusion, IL-6 and
      ET-1 are involved precociously in the development of intestinal IRI. Apoptosis
      was more frequently detected in G1 grafts by TUNEL-staining and by RT-PCR.

PMID- 21884348
TI  - Use of annual ABPM, and repeated carotid scan and echocardiography to monitor
      cardiovascular health over nine yr in pediatric and young adult renal transplant
      recipients.
AB  - In adult hypertensive patients, increased cIMT and LVH are independent risk
      factors for cardiovascular events. We have previously observed that in pediatric
      RTRs with tight control of BP, cIMT did not progress over time. This
      investigation is an extension of the aforementioned study aimed at re-examining
      cIMT and also reporting serial echocardiography results. Twenty-two RTRs aged 9.4
      +/- 3.3 yr at their baseline carotid scan underwent two additional vascular
      ultrasounds during a follow-up of 9.1 +/- 0.9 yr. Carotid scan and
      echocardiography examinations were carried out simultaneously with ABPM.
      Antihypertensive therapy was determined according to the recipient's ABPM
      results, which were performed at yearly intervals. Baseline cIMT was
      significantly greater in RTRs than in healthy controls. There was no statistical
      evidence of systematic changes in cIMT over time. At the last examination, 14 of
      17 RTRs with treated hypertension had controlled hypertension (prevalence 82%;
      95% CI, 56.5-96.2), and the overall prevalence of LVH was 4.5% (95% CI, -0.01 to
      23.5). The lack of progression of cIMT over time and the low prevalence of LVH
      might reflect the effect of long-standing BP control.

PMID- 21884349
TI  - Preparing nurses for the 21st century: reflecting on nursing shortages and other
      challenges in practice and education.

PMID- 21884351
TI  - Robotically speaking: Experts consider the current and future state of robotic
      surgery. Interview by Kevin D. Blanchet.

PMID- 21884352
TI  - Reflex anuria.

PMID- 21884353
TI  - 'Challenge' and 'threat' states in surgery: implications for surgical performance
      and training.

PMID- 21884354
TI  - Training in ureteroscopy: a critical appraisal of the literature.
AB  - The aim of the present review was to study factors influencing training and the
      maintenance of skills in performing ureteroscopy (URS). We searched on the
      following keywords in the Medline, Embase and Cochrane databases: renal or
      ureteric stone; ureteroscopy; endourology; educational; training; learning curve;
      expertise; skill; residency; practice; simulator; and robotics. We have defined,
      when possible, levels and grades of evidence, based on 2009 recommendations of
      the Oxford Centre for Evidence-Based Medicine. We found that technological
      advancement and surgeon experience is a predictive factor for success or
      complications of URS. Experience may be related to special endourology training,
      time passed after basic training and the number of procedures performed. Studies
      suggest that a resident must perform a certain amount of cases to gain
      proficiency with URS, but there is still a need for well designed studies for the
      learning curve of URS to be accurately defined. Training models may be useful for
      training in URS and stone disintegration. Stone centres that provide all the
      endoscopic treatment options seem to provide the best conditions to ensure a
      sufficient volume of patients required. Defining minimum requirements for
      training in URS and for maintaining certification is a major challenge, as is
      defining the learning curve in URS. Careful curriculum design in high-volume
      stone centres may be the key to optimizing URS training.

PMID- 21884356
TI  - The economic burden of prostate cancer.
AB  - In the present review we discuss expenditure on prostate cancer diagnosis,
      treatment and follow-up and evaluate the cost of prostate cancer and its
      management in different countries. Prostate cancer costs were identified from
      published data and internet sources. To provide up-to-date comparisons, costs
      were inflated to 2010 levels and the most recent exchange rates were applied. A
      high proportion of the costs are incurred in the first year after diagnosis; in
      2006, this amounted to 106.7-179.0 million euros (?) in the European countries
      where these data were available (UK, Germany, France, Italy, Spain and the
      Netherlands). In the USA, the total estimated expenditure on prostate cancer was
      9.862 billion US dollars ($) in 2006. The mean annual costs per patient in the
      USA were $10,612 in the initial phase after diagnosis, $2134 for continuing care
      and $33,691 in the last year of life. In Canada, hospital and drug expenditure on
      prostate cancer totalled C$103.1 million in 1998. In Australia, annual costs for
      prostate cancer care in 1993-1994 were 101.1 million Australian dollars.
      Variations in costs between countries were attributed to differences in incidence
      and management practices. Per patient costs depend on cancer stage at diagnosis,
      survival and choice of treatment. Despite declining mortality rates, costs are
      expected to rise owing to increased diagnosis, diagnosis at an earlier stage and
      increased survival. Unless new strategies are devised to increase the efficiency
      of healthcare provision, the economic burden of prostate cancer will continue to
      rise.

PMID- 21884357
TI  - What is the role of risk-adjusted funnel plots in the analysis of radical
      cystectomy volume-outcome relationships?
AB  - OBJECTIVE: * To explore whether risk-adjusted funnel plots are a useful adjunct
      to analyse volume-outcome data and to further facilitate our understanding of
      institutional performance data by combining funnel-plot methodology with an
      incremental statistical modelling approach. PATIENTS AND METHODS: * Risk-adjusted
      funnel plots were generated for mortality and re-intervention rates after
      elective radical cystectomy using administrative data from NHS Hospital Trusts
      between 2000/01 and 2006/07. Trusts were divided into volume tertiles based on
      their average annual cystectomy rate. * A funnel plot was produced for each of
      the following four incremental statistical models: model one (no adjustment),
      model two (adjusted for patient case mix variables), model three (case mix and
      'clustering' of patients) and model four (additional adjustment for institutional
      structural and process-of-care variables). RESULTS: * In the final complex model
      (model four), no Trusts had abnormally high mortality or re-intervention rates. *
      Comparison of the funnel plots showed the importance of adjusting for certain
      confounding factors, such as the surgeon, at the institutional level, before they
      could be labelled as having truly outlying performance. CONCLUSION: * Risk
      adjusted funnel plots have a useful role to play as a component of a
      methodological framework for investigating the volume-outcome relationship at the
      institutional level. They can act as a complementary method of validating data by
      displaying disaggregated outcomes at provider level and account for unmeasured
      confounders, so reducing the opportunity for spurious labelling of outliers.

PMID- 21884359
TI  - The dorsal venous complex (DVC): dorsal venous or dorsal vasculature complex?
      Santorini's plexus revisited.

PMID- 21884361
TI  - Preservation potential of ancient plankton DNA in Pleistocene marine sediments.
AB  - Recent studies have shown that ancient plankton DNA can be recovered from
      Holocene lacustrine and marine sediments, including from species that do not
      leave diagnostic microscopic fossils in the sediment record. Therefore, the
      analysis of this so-called fossil plankton DNA is a promising approach for
      refining paleoecological and paleoenvironmental information. However, further
      studies are needed to reveal whether DNA of past plankton is preserved beyond the
      Holocene. Here, we identified past eukaryotic plankton members based on 18S rRNA
      gene profiling in eastern Mediterranean Holocene and Pleistocene sapropels S1 (~9
      ka), S3 (~80 ka), S4 (~105 ka), and S5 (~125 ka). The majority of preserved ~400-
      to 500-bp-long 18S rDNA fragments of microalgae that were studied in detail (i.e.
      from haptophyte algae and dinoflagellates) were found in the youngest sapropel
      S1, whereas their specific lipid biomarkers (long-chain alkenones and dinosterol)
      were also abundant in sediments deposited between 80 and 124 ka BP. The late
      Pleistocene sediments mainly contained eukaryotic DNA of marine fungi and from
      terrestrial plants, which could have been introduced via the river Nile at the
      time of deposition and preserved in pollen grains. A parallel analysis of
      Branched and Isoprenoid Tetraethers (i.e. BIT index) showed that most of the
      organic matter in the eastern Mediterranean sediment record was of marine (e.g.
      pelagic) origin. Therefore, the predominance of terrestrial plant DNA over
      plankton DNA in older sapropels suggests a preferential degradation of marine
      plankton DNA.

PMID- 21884362
TI  - Legacies of recent environmental change in the benthic communities of Lake Joyce,
      a perennially ice-covered Antarctic lake.
AB  - Many Antarctic lakes provide habitat for extensive microbial mats that respond on
      various timescales to environmental change. Lake Joyce contains calcifying
      microbialites and provides a natural laboratory to constrain how environmental
      changes influence microbialite development. In Lake Joyce, depth-specific
      distributions of calcitic microbialites, organic carbon, photosynthetic pigments
      and photosynthetic potential cannot be explained by current growth conditions,
      but are a legacy of a 7-m lake level rise between 1973 and 2009. In the well
      illuminated margins of the lake, photosynthetically active benthic communities
      colonised surfaces submerged for just a few years. However, observed increases in
      accumulated organic material with depth from 5 to 20 m (2-40 mg ash-free dry
      weight cm(-2)) and the presence of decimetre-scale calcite microbialites at 20-22
      m depth, apparently related to in situ photosynthetic growth, are inconsistent
      with the current distributions of irradiance, photosynthetic pigments and mat
      photosynthetic potential (as revealed by pulse-amplitude-modulated fluorometry).
      The microbialites appeared photosynthetically active in 1986 and 1997, but were
      outside the depth zone where significant phototrophic growth was possible and
      were weakly photosynthetically competent in 2009. These complex microbial
      structures have persisted after growth has ceased, demonstrating how fluctuating
      environmental conditions and the hysteresis between environmental change,
      biological response and microbialite development can be important factors to
      consider when interpreting modern, and by inference ancient, microbially mediated
      structures.

PMID- 21884363
TI  - Analysis of growth directions of columnar stromatolites from Walker Lake, western
      Nevada.
AB  - Samples of digitate, branching, columnar stromatolites were collected from the
      steep sides and near horizontal top of four in situ boulders located on the
      southwestern side of Walker Lake, Nevada, to test the widely held assumption that
      stromatolite column formation represents a phototropic response. We would predict
      that the columns on the steeply dipping sides of the boulder would bend upwards
      toward the light during growth if phototropism was significant during
      stromatolite morphogenesis. Angle of growth measurements on >300 stromatolites
      demonstrate that the stromatolites grew nearly normal to their growth surface,
      regardless of the inclination of their growth surface. No significant differences
      in the distribution of growth angles between north-, south-, east-, or west
      facing samples were observed, and stromatolite lamina thickness did not
      systematically vary with position on the boulder. The lack of a strong
      phototropic response does not rule out a biological origin for the Walker Lake
      structures, but it does suggest that phototropic growth was not a dominant factor
      controlling stromatolite morphogenesis in these stromatolites and that column
      formation cannot be uniquely attributed as a phototropic response in
      stromatolites. It is interesting to note that the morphology of the stromatolites
      on the top of the boulder is identical to stromatolites on the steep sides.
      Stromatolite morphogenetic models that predict branching typically require a
      vertically directed sedimentary component, a feature that would have likely
      affected the stromatolites on the tops of the boulders, but not the sides,
      suggesting that other factors may be important in stromatolite morphogenesis.

PMID- 21884364
TI  - Energy sources for chemolithotrophs in an arsenic- and iron-rich shallow-sea
      hydrothermal system.
AB  - The hydrothermally influenced sediments of Tutum Bay, Ambitle Island, Papua New
      Guinea, are ideal for investigating the chemolithotrophic activities of micro
      organisms involved in arsenic cycling because hydrothermal vents there expel
      fluids with arsenite (As(III)) concentrations as high as 950 MUg L(-1) . These
      hot (99  degrees C), slightly acidic (pH ~6), chemically reduced, shallow-sea
      vent fluids mix with colder, oxidized seawater to create steep gradients in
      temperature, pH, and concentrations of As, N, Fe, and S redox species. Near the
      vents, iron oxyhydroxides precipitate with up to 6.2 wt% arsenate (As(V)). Here,
      chemical analyses of sediment porewaters from 10 sites along a 300-m transect
      were combined with standard Gibbs energies to evaluate the energy yields (
      DeltaG(r)) from 19 potential chemolithotrophic metabolisms, including As(V)
      reduction, As(III) oxidation, Fe(III) reduction, and Fe(II) oxidation reactions.
      The 19 reactions yielded 2-94 kJ mol(-1) e(-) , with aerobic oxidation of
      sulphide and arsenite the two most exergonic reactions. Although anaerobic As(V)
      reduction and Fe(III) reduction were among the least exergonic reactions
      investigated, they are still potential net metabolisms. Gibbs energies of the
      arsenic redox reactions generally correlate linearly with pH, increasing with
      increasing pH for As(III) oxidation and decreasing with increasing pH for As(V)
      reduction. The calculated exergonic energy yields suggest that micro-organisms
      could exploit diverse energy sources in Tutum Bay, and examples of micro
      organisms known to use these chemolithotrophic metabolic strategies are
      discussed. Energy modeling of redox reactions can help target sampling sites for
      future microbial collection and cultivation studies.

PMID- 21884365
TI  - Revisiting the dissimilatory sulfate reduction pathway.
AB  - Sulfur isotopes in the geological record integrate a combination of biological
      and diagenetic influences, but a key control on the ratio of sulfur isotopes in
      sedimentary materials is the magnitude of isotope fractionation imparted during
      dissimilatory sulfate reduction. This fractionation is controlled by the flux of
      sulfur through the network of chemical reactions involved in sulfate reduction
      and by the isotope effect associated with each of these chemical reactions.
      Despite its importance, the network of reactions constituting sulfate reduction
      is not fully understood, with two principle networks underpinning most isotope
      models. In this study, we build on biochemical data and recently solved crystal
      structures of enzymes to propose a revised network topology for the flow of
      sulfur through the sulfate reduction metabolism. This network is highly branched
      and under certain conditions produces results consistent with the observations
      that motivated previous sulfate reduction models. Our revised network suggests
      that there are two main paths to sulfide production: one that involves the
      production of thionate intermediates, and one that does not. We suggest that a
      key factor in determining sulfur isotope fractionation associated with sulfate
      reduction is the ratio of the rate at which electrons are supplied to subunits of
      Dsr vs. the rate of sulfite delivery to the active site of Dsr. This reaction
      network may help geochemists to better understand the relationship between the
      physiology of sulfate reduction and the isotopic record it produces.

PMID- 21884366
TI  - The author's authentic voice.

PMID- 21884367
TI  - Integrating genomics into undergraduate nursing education.
AB  - PURPOSE: To prepare the next generation of nurses, faculty are now faced with the
      challenge of incorporating genomics into curricula. Here we discuss how to meet
      this challenge. ORGANIZING CONSTRUCT: Steps to initiate curricular changes to
      include genomics are presented along with a discussion on creating a genomic
      curriculum thread versus a standalone course. Ideas for use of print material and
      technology on genomic topics are also presented. Information is based on review
      of the literature and curriculum change efforts by the authors. CONCLUSIONS: In
      recognition of advances in genomics, the nursing profession is increasing an
      emphasis on the integration of genomics into professional practice and
      educational standards. Incorporating genomics into nurses' practices begins with
      changes in our undergraduate curricula. Information given in didactic courses
      should be reinforced in clinical practica, and Internet-based tools such as
      WebQuest, Second Life, and wikis offer attractive, up-to-date platforms to
      deliver this now crucial content. CLINICAL RELEVANCE: To provide information that
      may assist faculty to prepare the next generation of nurses to practice using
      genomics.

PMID- 21884368
TI  - Strategies to prepare faculty to integrate genomics into nursing education
      programs.
AB  - PURPOSE: Faculty knowledge of genomics, learner competencies, and program
      requirements for nursing education are described to assist educators in
      introducing genomic information into nursing undergraduate, graduate,
      postgraduate, and continuing education programs regardless of geographic
      location. Selected programs in the United States and the United Kingdom are
      described to illustrate successful approaches used by nursing faculty to enhance
      their genomic knowledge in order to increase application of genetic and genomic
      content within nursing education curricula. ORGANIZING CONSTRUCT: Nursing
      education guidelines and nursing competencies provide benchmarks for educators in
      planning genetic and genomic curriculum content and expected learner outcomes.
      METHODS: Elements within competencies from the United States and the United
      Kingdom are reviewed to provide the framework for faculty knowledge. Strategies
      to address development of faculty knowledge and expertise are suggested.
      Continuing education faculty development programs and strategies to develop
      doctorally prepared nurse scientists who will educate future students in the
      profession are described. CONCLUSIONS: Multiple faculty who are prepared to
      implement education on genetic and genomic topics are needed at all levels of
      nursing education. Faculty networking and application of genomic principles to
      nursing are key elements for sustaining nursing education to produce a nursing
      workforce that can apply essential genomic knowledge. CLINICAL RELEVANCE: There
      is an urgent need to offer genomics in accessible and effective education for
      nursing practice to optimize health outcomes regardless of geographic location.

PMID- 21884369
TI  - The meaning of breast cancer risk for African American women.
AB  - PURPOSE: To describe African American women's experience of being at high risk
      for breast cancer. DESIGN: A hermeneutic phenomenological approach was used to
      guide in-depth interviews and analysis. Methods to ensure trustworthiness and
      rigor were included. METHODS: Open interviews were conducted with 20 African
      American women who were at high risk for breast cancer (family history, personal
      history, genetic mutation). They were recruited from a cancer risk clinic and
      community-based settings. Data were transcribed verbatim, and themes were labeled
      among and between all interviews. FINDINGS: Five themes were identified: (a) life
      changing experience; (b) relationships: fears, support, and concerns; (c) the
      healthcare experience; (d) raising awareness; and (e) strong faith. CONCLUSIONS:
      Young women at high risk for breast cancer have unique emotional and support
      needs that are shaped by stage in life, relationships with significant others,
      their faith, and interactions with the healthcare delivery system. CLINICAL
      RELEVANCE: Breast cancer does occur in young women. This highlights the need for
      timely and sensitive approaches to care when young women present with breast
      health concerns or abnormal breast findings.

PMID- 21884370
TI  - Effects of gender on burden among caregivers of Alzheimer's patients.
AB  - PURPOSE: This study was conducted to determine the effects of gender on caregiver
      burden among caregivers of persons with Alzheimer's disease. DESIGN: Comparative
      descriptive study. METHODS: Factors affecting the burden of female and male
      caregivers (age, total duration of caregiving, mean duration of daily caregiving,
      education, income, employment status, age of the patients cared for, and Mini
      Mental State Examination [MMSE] and Neuropsychiatric Inventory [NPI] scores) were
      similar (p > .05). The sample consisted of 120 female and 72 male caregivers of
      patients with Alzheimer's disease. Data were collected from patients by means of
      the MMSE and demographic variables, and data from the Caregiver Burden Inventory
      [CBI] and NPI were obtained from caregivers, as well as from face-to-face
      interviews using a questionnaire. Descriptive statistics and t-tests were used to
      describe and analyze data. FINDINGS: Female caregivers had significantly higher
      scores for caregiver burden than their male counterparts (p= .002). Subscale
      analysis on the CSI revealed that female caregivers had significantly higher
      scores for caregiver burden than male caregivers on time dependence (p= .040),
      developmental (p= .002), physical (p= .001), and social burdens (p= .045). No
      difference was found with respect to emotional burden (p= .718). CONCLUSIONS:
      Results of this study suggest that female caregivers are subjected to a higher
      level of caregiver burden than male caregivers in Turkey. In subscales, female
      caregivers experienced more burden than male caregivers in the time dependence,
      developmental, physical, and social burdens. Emotional burden was similar in both
      genders. CLINICAL RELEVANCE: Although caregiver burden has been a much debated
      issue for many years, it is a relatively new topic in Turkey. In order to provide
      appropriate care for the patient's and family's cultural values and needs, more
      studies are needed to be conducted on family members giving care to Alzheimer's
      patients. It is thought that the findings of the present study will facilitate
      cross-cultural comparisons and culture-oriented care planning.

PMID- 21884371
TI  - Delineation of self-care and associated concepts.
AB  - PURPOSE: The purpose of this paper is to delineate five concepts that are often
      used synonymously in the nursing and related literature: self-care, self
      management, self-monitoring, symptom management, and self-efficacy for self-care.
      METHOD: Concepts were delineated based on a review of literature, identification
      of relationships, and examination of commonalities and differences. FINDINGS:
      More commonalities than differences exist among self-care, self-management, and
      self-monitoring. Symptom management extends beyond the self-care concepts to
      include healthcare provider activities. Self-efficacy can mediate or moderate the
      four other concepts. Relationships among the concepts are depicted in a model.
      CONCLUSIONS: A clearer understanding of the overlap, differences, and
      relationships among the five concepts can provide clarity, direction and
      specificity to nurse researchers, policy makers, and clinicians in addressing
      their goals for health delivery. CLINICAL RELEVANCE: Concept clarity enables
      nurses to use evidence that targets specific interventions to individualize care
      toward achieving the most relevant goals.

PMID- 21884372
TI  - The effect of the odor of breast milk on the time needed for transition from
      gavage to total oral feeding in preterm infants.
AB  - PURPOSE: The aim of this study was to investigate the effect of the application
      of the odor of breast milk in preterm infants during gavage feeding on the period
      of transition to total oral feeding. DESIGN: This prospective experimental study
      was performed on a total of 80 preterm infants: 40 infants in the study group and
      40 in the control group. METHODS: This experimental study was performed in
      eastern Turkey at the Neonatal Intensive Care and Premature Unit of a university
      hospital between September 2007 and December 2008. The demographic data were
      collected via a questionnaire, and an intervention and follow-up table was
      prepared by the researcher based on relevant literature. The study was approved
      by the local institution, and written informed consent was obtained from all
      parents. FINDINGS: The findings of the study indicated that the preterm infants
      who were stimulated by the odor of breast milk during gavage feeding transitioned
      to oral feeding 3 days earlier than control subjects. Moreover, the mean
      hospitalization time of these infants was 4 days shorter. CONCLUSIONS: The
      results show that stimulation with breast milk odor is an effective method for
      decreasing transition of preterm infants from gavage to oral feeding. CLINICAL
      RELEVANCE: Nurses can train mothers to pump their breast milk, stimulate their
      infants with the odor of their breast milk, and feed it to their infants in the
      premature unit. This may lead to a quicker transition to oral feeding.

PMID- 21884373
TI  - Advancing the biobehavioral research of fatigue with genetics and genomics.
AB  - PURPOSE: To examine phenotypic considerations in the study of fatigue and to
      explore significant issues affecting the extension of biobehavioral research of
      fatigue by the inclusion of genetic and genomic markers. THEORETICAL
      ORGANIZATION: Fatigue is a condition that has an adverse effect on quality of
      life that has been a focus of nursing inquiry. Yet, the study of fatigue has been
      stymied by the lack of phenotypic clarity. To expand the biobehavioral inquiry of
      fatigue, phenotypic clarity is needed. In addition, examining genomic factors
      associated with fatigue may help to elucidate the pathophysiology of fatigue and,
      in the future, lead to targeted interventions that address the molecular basis of
      fatigue. CONCLUSIONS: Given that nursing has been at the forefront of the study
      of fatigue, nurse scientists should consider enhancing phenotypic clarity by the
      development of a case-definition and use of a core measure of fatigue, one that
      can be augmented by condition- or population-specific measures as needed.
      Following the establishment of phenotypic clarity, the integration of genomics
      into biobehavioral research offers an opportunity for further clarity of
      phenotypes and for theoretical specification of the pathophysiology of conditions
      such as fatigue. CLINICAL RELEVANCE: The development of targeted interventions
      for fatigue depend on a more precise definition of fatigue and a better
      understanding of the biologic processes that contribute to its development and
      persistence.

PMID- 21884374
TI  - Subjective burden and cultural motives for caregiving in informal caregivers of
      older people.
AB  - PURPOSE: The aims of this study were to investigate variables related to cultural
      caregiving motives (obligation and reciprocity) and to analyze the relationship
      between these cultural caregiving motives and subjective burden in informal
      caregivers of disabled older people. DESIGN AND METHODS: A secondary analysis of
      the last cross-sectional Spanish survey of informal caregivers of older people
      (n= 1,284, probability sample) was performed. Measurements included
      sociodemographic characteristics of caregivers (gender, age, relationship with
      care recipient, primary caregiver status, and duration of caregiving), intensity
      of care (hours per week, type of care, and number of activities of daily living
      [ADL] assisted), cultural motives for caregiving (obligation and balanced
      reciprocity), and caregiver subjective burden. Statistical analyses included
      descriptive (means, percentages, and 95% confidence intervals), bivariate (chi
      square test), and multivariate (binary logistic regression) analyses. FINDINGS:
      Obligation and reciprocity were higher in spouses than in other relatives and in
      nonrelatives and obligation increased with age as well as providing help with
      ADL. Balanced reciprocity was high in men. Obligation was not related with
      subjective burden, whereas balanced reciprocity was positively related.
      CONCLUSIONS: Reciprocity had a protective effect on subjective burden. No
      cultural differences have been found on this issue. Obligation may be a
      multidimensional concept that encompasses personal beliefs and social demands.
      CLINICAL RELEVANCE: Balanced reciprocity is useful for early prevention and early
      intervention of subjective burden and must be included in nursing care plans for
      caregivers. Cultural factors support the comprehension of the caregiving process.

PMID- 21884375
TI  - Comparison of hospital admission medication lists with primary care physician and
      outpatient pharmacy lists.
AB  - PURPOSE: Medication reconciliation is a process to reduce errors and harm
      associated with loss of medication information as the patient enters and moves
      through the healthcare system. This study examines medication list accuracy upon
      hospital admission. DESIGN: This prospective study enrolled 75 English-speaking
      medical and surgical patients (18 years of age or older) who were taking
      prescription medications. The study took place at a rural, tertiary teaching
      hospital in the northeastern United States. Data collection occurred from
      November 2006 to March 2009. METHODS: Nursing admission team medication lists
      were reconciled with primary care physician (PCP) and outpatient pharmacy (OP)
      lists. Outcome measures were accuracy of medication history generated by
      admission nurses (ANs) compared with PCP and OP lists, and identification of
      factors influencing probability of accurate medication list generation by ANs.
      The Generalized Estimating Equations modeling approach was used to compare AN,
      OP, and PCP medication list accuracy. Additionally, sex and age were analyzed as
      covariates and included in the model. FINDINGS: Forty-five males and 30 females
      (N= 75) with a mean age of 60 years (SD 15) participated. Fifty-seven subjects
      (76%) used over-the-counter or herbal medications, but the AN recorded only 31
      (41%) cases. Patients received outpatient care from 1 to 12 providers. Forty
      patients (67%) obtained medications from one pharmacy, 22 (29%) from two, and 3
      (4%) from three pharmacies. OP medication lists were completely accurate more
      often than PCP but not AN lists (19/75 [25%] OP vs. 6/75 [8%] PCP vs. 14/75 [19%]
      AN; 95% confidence interval [CI] of the difference [0.07, 0.50]). No difference
      between AN and PCP list accuracy was found. Completely accurate AN lists were
      more than twice as likely with male and younger patients (95% CI of the
      difference [1.07, 6.22] and [0.94, 0.99], respectively). CONCLUSIONS: Like other
      studies, this study showed admission medication reconciliation lists are often
      inaccurate. Our results suggest that verification of admission medication lists
      with outpatient provider lists may improve accuracy. Patients, with guidance from
      outpatient care providers, should assume accountability for maintaining accurate
      medication lists. A secure, universal, interactive electronic medical record may
      be a future solution for organizing and sharing medication data between
      providers. CLINICAL RELEVANCE: Medication reconciliation upon inpatient admission
      remains a high-volume and high-acuity problem. We found that not only hospital
      medication lists, but source lists, including those maintained by the patient,
      the PCP, and the OP, are vastly inaccurate.

PMID- 21884377
TI  - Successful techniques for using human patient simulation in nursing education.
AB  - PURPOSE: The purpose of this paper was to explore techniques used successfully
      for human simulation exercises in nursing education. DESIGN AND METHODS: An
      integrated review of current literature was completed using the Cumulative Index
      to Nursing and Allied Health Literature (CINAHL) with Full Text and PubMed
      databases to identify studies that used simulation successfully in nursing
      curriculum. FINDINGS AND CONCLUSIONS: Human patient simulation can be used
      successfully as an instructional method in nursing education. While no single
      process was proven to be superior, there are techniques which have been used
      effectively. CLINICAL RELEVANCE: Nursing educators are challenged with
      discovering ways to facilitate the education of their students. Human patient
      simulation can be a valuable tool. More research is needed to fully develop this
      promising educational avenue.

PMID- 21884376
TI  - Quality of care and patient satisfaction in hospitals with high concentrations of
      black patients.
AB  - PURPOSE: To examine the influence of nursing-specifically nurse staffing and the
      nurse work environment-on quality of care and patient satisfaction in hospitals
      with varying concentrations of Black patients. DESIGN: Cross-sectional secondary
      analysis of 2006-2007 nurse survey data collected across four states (Florida,
      Pennsylvania, New Jersey, and California), the Hospital Consumer Assessment of
      Healthcare Providers and Systems survey, and administrative data. Global analysis
      of variance and linear regression models were used to examine the association
      between the concentration of Black patients on quality measures (readiness for
      discharge, patient or family complaints, health care-associated infections) and
      patient satisfaction, before and after accounting for nursing and hospital
      characteristics. RESULTS: Nurses working in hospitals with higher concentrations
      of Blacks reported poorer confidence in patients' readiness for discharge and
      more frequent complaints and infections. Patients treated in hospitals with
      higher concentrations of Blacks were less satisfied with their care. In the fully
      adjusted regression models for quality and patient satisfaction outcomes, the
      effects associated with the concentration of Blacks were explained in part by
      nursing and structural hospital characteristics. CONCLUSIONS: This study
      demonstrates a relationship between nursing, structural hospital characteristics,
      quality of care, and patient satisfaction in hospitals with high concentrations
      of Black patients. CLINICAL RELEVANCE: Consideration of nursing factors, in
      addition to other important hospital characteristics, is critical to
      understanding and improving quality of care and patient satisfaction in minority
      serving hospitals.

PMID- 21884378
TI  - Development and psychometric validation of the general practice nurse
      satisfaction scale.
AB  - PURPOSE: To develop an instrument to assess consumer satisfaction with nursing in
      general practice to provide feedback to nurses about consumers' perceptions of
      their performance. DESIGN: Prospective psychometric instrument validation study.
      METHODS: A literature review was conducted to generate items for an instrument to
      measure consumer satisfaction with nursing in general practice. Face and content
      validity were evaluated by an expert panel, which had extensive experience in
      general practice nursing and research. Included in the questionnaire battery was
      the 27-item General Practice Nurse Satisfaction (GPNS) scale, as well as
      demographic and health status items. This survey was distributed to 739 consumers
      following intervention administered by a practice nurse in 16 general practices
      across metropolitan, rural, and regional Australia. Participants had the option
      of completing the survey online or receiving a hard copy of the survey form at
      the time of their visit. These data were collected between June and August 2009.
      FINDINGS: Satisfaction data from 739 consumers were collected following their
      consultation with a general practice nurse. From the initial 27-item GPNS scale,
      a 21-item instrument was developed. Two factors, "confidence and credibility" and
      "interpersonal and communication" were extracted using principal axis factoring
      and varimax rotation. These two factors explained 71.9% of the variance.
      Cronbach's alpha was 0.97. CONCLUSIONS: The GPNS scale has demonstrated
      acceptable psychometric properties and can be used both in research and clinical
      practice for evaluating consumer satisfaction with general practice nurses.
      RELEVANCE TO CLINICAL PRACTICE: Assessing consumer satisfaction is important for
      developing and evaluating nursing roles. The GPNS scale is a valid and reliable
      tool that can be utilized to assess consumer satisfaction with general practice
      nurses and can assist in performance management and improving the quality of
      nursing services.

PMID- 21884381
TI  - Patterns and correlates of same-sex sexual activity among U.S. teenagers and
      young adults.
AB  - CONTEXT: Little is known about the prevalence and correlates of same-sex sexual
      activity among teenagers and young adults, particularly those who do not identify
      themselves as gay, lesbian or bisexual. Effective interventions to prevent STDs
      require accurate understanding of youths' sexual behavior. METHODS: Descriptive
      and regression analyses of data from the 2002 National Survey of Family Growth
      examined patterns and correlates of same-sex sexual activity among a sample of
      2,688 never-married, noncohabiting men and women aged 15-21. Same-sex behavior
      was assessed separately by gender, as well as by heterosexual experience and
      sexual attraction and identity. RESULTS: Eleven percent of women and 4% of men
      reported same-sex sexual experience. Youth who were attracted only to the
      opposite sex had a decreased likelihood of reporting same-sex activity (rate
      ratio, 0.1 for each gender), while women and men who identified themselves as
      homosexual or bisexual had an elevated likelihood of such activity (5.1 and 5.9,
      respectively). However, among women who were attracted exclusively to men, those
      who had had heterosexual sex were more than four times as likely as those who had
      not to have engaged in same-sex activity. Finally, among youth who reported any
      same-sex attraction, women and men who said they were homosexual or bisexual had
      an elevated likelihood of having engaged in same-sex behavior (4.7 and 5.6,
      respectively). CONCLUSION: A significant proportion of "straight" youth engage in
      same-sex activity, and so information on risks associated with such behavior
      should be included in sex education programs and targeted to all youth.

PMID- 21884382
TI  - The number of recent sex partners among bisexual men in the United States.
AB  - CONTEXT: Little is known regarding bisexual men's number of recent sex partners,
      a risk factor for HIV and other STDs. Furthermore, it is unclear if bisexual men
      have more partners than heterosexual or homosexual men, and whether partner
      number varies by measures of sexual behavior, identity and attraction. METHODS:
      Sexual orientation-defined separately by sexual behavior during the past year,
      identity and attraction-was assessed for 3,875 sexually active men aged 15-44 who
      had participated in the 2002 National Survey of Family Growth. Chi-square and t
      tests examined differences in background characteristics, behavioral risk factors
      and number of past-year sex partners by sexual orientation according to each
      definition. Multivariate ordinary least-squares regression was used to assess
      predictors of the number of partners. RESULTS: When sexual identity and
      attraction were controlled for, behaviorally bisexual men were predicted to have
      had 3.1 more past-year partners than behaviorally heterosexual men and 2.6 more
      than behaviorally homosexual men. After controlling for sexual identity and
      behavior, bisexual-attracted men had had 0.7 fewer partners than homosexual
      attracted men. In a model including background characteristics and behavioral
      risk factors, behaviorally bisexual men were predicted to have had 2.5-2.6 more
      partners than others. Neither bisexual identity nor bisexual attraction
      independently predicted the number of recent partners. CONCLUSION: The way in
      which bisexuality relates to men's number of recent sex partners depends on how
      sexual orientation is measured. Interventions to reduce behaviorally bisexual
      men's number of partners will likely lessen their risk for HIV and other STDs.

PMID- 21884383
TI  - Bacterial STDs and perceived risk among sexual minority young adults.
AB  - CONTEXT: Most sexual health interventions focus on heterosexual sexual risk
      behavior. Health practitioners face a lack of information about the sexual health
      of sexual minority young adults (aged 18-26). METHODS: Three indicators of sexual
      minority status (identity, behavior and romantic attractions) were assessed in
      10,986 young adults who participated in Wave 3 of the National Longitudinal Study
      of Adolescent Health (2001-2002). Logistic regression analyses examined
      associations between these indicators and individuals' perceived risk for STDs
      and actual infection with STDs. Data from the 1,154 respondents who had current
      or recent bacterial STDs were investigated further to determine whether they had
      underestimated their risk. RESULTS: Outcomes varied by sexual minority status
      indicator and by sex. Bisexual females had significantly higher odds of STDs than
      heterosexual females (odds ratios, 1.4), and females attracted to both sexes had
      significantly higher odds of STDs than females attracted only to males (1.8). In
      contrast, none of the sexual minority status indicators predicted STDs for males.
      Among respondents who had an STD, females who reported only same-sex sexual
      relationships were more likely to believe they were at very low risk for STDs
      than were females reporting only opposite-sex sexual relationships (17.2);
      homosexual females had a higher likelihood of this outcome than heterosexual
      females (19.7). CONCLUSIONS: Health practitioners need to assist sexual minority
      young adults, particularly females, in under-standing their risk for STDs and in
      taking safer-sex precautions.

PMID- 21884384
TI  - Reproductive health characteristics of marijuana and cocaine users: results from
      the 2002 National Survey of Family Growth.
AB  - CONTEXT: Illicit drug use is associated with risky sexual behaviors in
      adolescents and young adults. However, few studies have examined these
      associations among drug users of all reproductive ages, using a control group of
      nonusers. METHODS: Associations between marijuana and cocaine use, and outcomes
      related to sexual behaviors and reproductive health, were assessed using data
      from the 2002 National Survey of Family Growth. Overall, 4,928 men and 7,643
      women aged 15-44 were interviewed. Chi-square tests, t tests and multivariable
      logistic regression analyses were used; in supplementary analyses, men and women
      were stratified by age-group (25 or younger, and older than 25), to capture the
      understudied older adults who use drugs. RESULTS: Twenty-seven percent of men and
      16% of women reported use of marijuana or cocaine in the last year. Drug users
      were younger than nonusers at first vaginal sex (mean, 15.2-16.1 vs. 17.3-17.5
      years) and were more likely to have engaged in risky sexual behaviors in the last
      year, including having had sex with a nonmonogamous partner (odds ratios, 3.3-5.2
      for men and 2.9-6.5 for women), while high on alcohol or drugs (10.1-18.0 and 8.1
      24.2), or in exchange for money or drugs (2.7-2.8 and 2.3-9.2). They also were
      more likely to have undergone STD testing or treatment. Drug use was associated
      with risky sexual behaviors in both age-groups. CONCLUSION: Programs aimed at
      reducing sexual risks among drug users should address the behaviors of men and
      women of all reproductive ages.

PMID- 21884385
TI  - Racial and ethnic disparities in contraceptive method choice in California.
AB  - CONTEXT: Unintended pregnancy, an important public health issue,
      disproportionately affects minority populations. Yet, the independent
      associations of race, ethnicity and other characteristics with contraceptive
      choice have not been well studied. METHODS: Racial and ethnic disparities in
      contraceptive use among 3,277 women aged 18-44 and at risk for unintended
      pregnancy were assessed using 2006-2008 data from of the California Women's
      Health Survey. Sequential logistic regression analyses were used to examine the
      independent and cumulative associations of racial, ethnic, demographic and
      socioeconomic characteristics with method choice. RESULTS: Differences in
      contraceptive use persisted in analyses controlling for demographic and
      socioeconomic characteristics. Blacks and foreign-born Asians were less likely
      than whites to use high-efficacy reversible methods-that is, hormonals or IUDs
      (odds ratio, 0.5 for each). No differences by race or ethnicity were found
      specifically for IUD use in the full model. Blacks and U.S.-born Hispanics were
      more likely than whites to choose female sterilization (1.9 and 1.7,
      respectively), while foreign-born Asians had reduced odds of such use (0.4).
      Finally, blacks and foreign-born Asians were less likely than whites to rely on
      male sterilization (0.3 and 0.1, respectively). CONCLUSIONS: Socioeconomic
      factors did not explain the disparities in method choice among racial and ethnic
      groups. Intervention programs that focus on improving contraceptive choice among
      black and, particularly, Asian populations need to be developed, as such programs
      have the potential to reduce the number of unintended pregnancies that occur
      among these high-risk groups.

PMID- 21884386
TI  - Race, ethnicity and differences in contraception among low-income women: methods
      received by Family PACT Clients, California, 2001-2007.
AB  - CONTEXT: The extent to which racial and ethnic differences in method choice are
      associated with financial barriers is unclear. Understanding these associations
      may provide insight into how to address racial and ethnic disparities in
      unintended pregnancy. METHODS: Claims data from the California Family PACT
      program, which provides free family planning services to low-income residents,
      were used to determine the proportions of women receiving each type of
      contraceptive method in 2001-2007. Bivariate and multivariate analyses were
      performed to identify associations between women's race and ethnicity and the
      primary contraceptive method they received in 2007. RESULTS: Compared with white
      women, blacks and Latinas were less likely to receive oral contraceptives (odds
      ratios, 0.4 and 0.6, respectively) and the contraceptive ring (0.7 and 0.5), and
      more likely to receive the injectable (1.6 and 1.4) and the patch (1.6 and 2.3).
      Black women were less likely than whites to receive the IUD (0.5), but more
      likely to receive barrier methods and emergency contraceptive pills (2.6);
      associations were similar, though weaker, for Latinas. Racial and ethnic
      disparities in receipt of effective methods declined between 2001 and 2005,
      largely because receipt of the patch (which was introduced in 2002) was higher
      among minority than white women. CONCLUSION: Although Family PACT eliminates
      financial barriers to method choice, the methods women received differed
      substantially by race and ethnicity in this low-income population. The reduction
      in racial and ethnic disparities following introduction of the patch suggests
      that methods with novel characteristics may increase acceptability of
      contraceptives among minority women.

PMID- 21884387
TI  - Legal abortion worldwide in 2008: levels and recent trends.
AB  - CONTEXT: Periodic assessments of abortion incidence are essential for monitoring
      trends in unintended pregnancy and gaps in contraceptive services and use.
      METHODS: Statistics and estimates of legal induced abortions in 2008 were
      compiled for 64 of the 77 countries in which legal abortion is generally
      available; the 64 are home to 98% of women aged 15-44 who live in the countries
      eligible for inclusion. Data sources included reports or completed questionnaires
      from national statistical offices and nationally representative surveys. The
      completeness of official figures was assessed by in-country and regional experts.
      Trends since 1996 and 2003 were examined. RESULTS: Of the 77 countries with
      liberal abortion laws, 36 are in the developing world. In 2008, abortion rates in
      the 25 countries with complete records-all of which were developed-ranged from
      seven (Germany and Switzerland) to 30 (Estonia) per 1,000 women aged 15-44.
      Abortion rates declined in about half of the 20 countries with consistently
      reliable information on trends between 1996 and 2008; declines were generally
      steeper than increases, although the pace of decline slowed after 2003. The
      highest observed abortion rates were in developing countries with incomplete
      estimates. For most developing countries that had liberal laws, the reported
      abortion rates were incomplete and varied widely. CONCLUSIONS: High abortion
      rates in some countries, and small increases in rates in others, indicate a great
      need for more effective family planning services for these populations. Reliable
      data collection systems, needed to ensure that trends can be effectively
      monitored, are lacking in many countries.

PMID- 21884388
TI  - Working with Dr. Tiller: staff recollections of Women's Health Care Services of
      Wichita.

PMID- 21884396
TI  - Youth gangs: reason for concern.

PMID- 21884398
TI  - Walking a fine line: Forensic mental health practitioners' experience of working
      with correctional officers.
AB  - This paper explores mental health professionals' experiences working with
      correctional staff--one aspect of an interdisciplinary phenomenological study of
      ethical practice in forensic psychiatry. Professionals describe this relationship
      as coexisting within the system, despite their often conflicting roles. In
      correctional officers' overt concern for custody and control, practitioners can
      perceive a "paramilitary mentality" with which they struggle to work. Conversely,
      practitioners can experience conflict with security personnel for appearing "too
      caring" or "too sympathetic" to offenders--being "con-lovers." The balance
      practitioners establish between working with inmates and working alongside
      facility security is one of walking a fine line.

PMID- 21884399
TI  - Really not even a decision any more: Late adolescent narratives of implied sexual
      consent.
AB  - Sexual activity without clear consent, as one aspect of violence against women,
      is a significant global issue, especially during adolescence when young people
      are developing their values and beliefs about sexual activity and sexual norms.
      This narrative inquiry was performed to investigate influences on the sexual
      decision-making of late adolescents. Ten late adolescent females between the ages
      of 18 and 22 comprised the final sample. The results included the main finding
      that in the majority of these adolescents' sexual encounters, sexual consent was
      implied by the situation instead of being clearly stated. Inability to
      communicate with partners and the influence of alcohol were identified as
      contributing factors to implied sexual consent. Additionally, there was a
      pervasive normalization and acceptance of this type of nonconsensual sexual
      activity, and no one labeled these actions as rape or assault. IMPLICATIONS:
      Providers who work with adolescents need to assess sexual behaviors in greater
      detail and recognize that complex social factors and individual characteristics
      may contribute to an environment in which adolescents are at risk for
      nonconsensual sexual activity. Sexual violence education programs need to include
      information on negotiation and communication skills that will help adolescents
      mediate complicated interpersonal situations.

PMID- 21884400
TI  - Accidental deaths occurring in bed: review of cases and proposal of preventive
      strategies.
AB  - The bed is thought to be a safe place, but posses a number of risks that can
      cause deaths. To identify the causes of accidental death in bed and propose
      strategies for the prevention of further accidents, we surveyed and analyzed the
      literature on accidental deaths in bed from Japan and abroad, as well as legal
      cases related to accidental death in bed in Japan. A search of the medical
      literature in Japan (1983-2007), abroad (1976-2007), and Japan's legal cases
      (1989-2007) located 39 cases. The vast majority of accidental deaths in bed occur
      among infants and elderly individuals with neurologic disorders. The main causes
      of death within these two groups are head injuries caused by falls from a bed and
      asphyxia caused by pressure to the neck when wedged against a bed rail. It is
      necessary to focus on prevention of falls from bed and prevention of asphyxia
      caused by bed rails in the case of infants and elderly individuals with
      neurologic disorders. Infants should be placed to sleep in beds designed for
      their ages and placed on their back. Elderly individuals need to sleep in beds
      with properly fitting bed rails to reduce wedging.

PMID- 21884401
TI  - An examination of SANE data: clinical considerations based on victim-assailant
      relationship.
AB  - The current study analyzes adult female sexual assault data, collected by sexual
      assault nurse examiners (SANEs) in New Hampshire, United States, between 1997 and
      2007. The purposes of this study were to (1) explore the relationship between
      patient and assailant, (2) examine patients' physical findings according to
      assailant type, (3) describe characteristics of both the patients and the
      assaults, and (4) make care recommendations. Secondary analysis was conducted on
      data gathered by SANEs from responses to a standardized questionnaire based on
      the medical/forensic examination of each patient over an 11-year period. Of the
      741 women in this study, 53% were sexually assaulted by a nonstranger, 18% were
      assaulted by an intimate partner, and 11% were assaulted by a stranger. The
      relationship between patient and assailant is an important variable that requires
      SANEs to take a closer look at assessing for lethality, and assisting with safety
      planning, intervention, and treatment for victims.

PMID- 21884402
TI  - DNA testing of sexual assault evidence: the laboratory perspective.
AB  - The availability of DNA testing has dramatically changed the way that crimes are
      investigated. DNA results can link offenders to their crimes, exonerate
      wrongfully accused individuals, identify mass fatality victims and more. In the
      case of sexual assault, DNA evidence alone cannot prove that a sexual assault has
      occurred. DNA analysis can only reveal whether a person's DNA is, or is not,
      present. In this paper, the authors provide readers with an overview of the
      advantages and limitations of DNA analysis, the importance of proper evidence
      collection, the technologies available, and the amount of sample needed for
      testing. Through proper evidence collection and quality laboratory services, the
      full value of DNA will be realized.

PMID- 21884403
TI  - Autopsy features of sudden death due to isolated eosinophilic coronary arteritis:
      report of two cases.
AB  - Isolated eosinophilic coronary arteritis (IECA) has been reported as a cause of
      sudden unexpected death and has recently been recognized as a newly emerging
      vasculitic disease. We identified eight case reports and two case series of
      sudden death due to IECA in the medical literature and we present two new cases
      of sudden death due to IECA. Our cases further support the proposition that IECA
      may be a newly emerging distinct vasculitis, which can go undiagnosed and present
      with sudden death. At autopsy IECA presents with isolated non-necrotizing
      predominantly eosinophilic inflammation of the coronary arteries without
      vasculitis in any other organ or blood vessel. The mean age of death of our two
      cases and the previously reported cases of IECA is 47 years, comprising 13
      females and 3 males with a range of 34-64 years. All cases died suddenly and
      unexpectedly. Past medical history of recurrent chest pain was documented in 63%
      of cases. The patho-etiology of IECA may involve an aberrant immune response or
      hypersensitivity reaction. Elucidation of the pathology of IECA may be translated
      into definitive diagnostic, interventional, and preventive modalities, which will
      further reduce the person years of life lost to heart disease.

PMID- 21884405
TI  - Alemtuzumab shows promise as off-label induction therapy.

PMID- 21884408
TI  - Minor antigens on transfused RBCs crossprime CD8 T cells but do not induce full
      effector function.
AB  - HLA-matched bone marrow transplantation (BMT) is a cure for nonmalignant
      hematological disorders; however, rejection rates are high and correlate with the
      number of antecedent transfusions. Recently, using murine models, we reported
      that minor antigens (mHAs) in transfused leukoreduced red blood cell (RBC) or
      platelet units induce rejection of subsequent BMT. To study RBCs as an immunogen,
      we utilized transgenic donors that express a model mHA selectively on RBCs (HOD
      mouse). Transfusion of HOD blood did not induce BMT rejection of marrow that
      shared mHAs with the HOD RBCs. Similarly, no endogenous anti-HOD CD8(+) T-cell
      response was detected with antigen-specific tetramer reagents. Adoptively
      transferred OT-I T cells rapidly expanded after HOD blood transfusion; however,
      only a semi-effector phenotype was observed (tumor necrosis factor-alpha and
      interferon-gamma secretion, but essentially no Granzyme B). After initial
      expansion, OT-I T cells contracted rapidly to very low levels. A similar trend
      was observed by in vivo CTL assay, with only transient lytic activity. Together,
      these data indicate that RBCs may not be the component of RBC units that induces
      BMT rejection, and suggest that contaminating platelets or leukocytes may be
      responsible.

PMID- 21884409
TI  - Emergence of Cryptococcus gattii--Pacific Northwest, 2004-2010.

PMID- 21884410
TI  - [Expert consensus: Histopathological diagnostics of malignant melanoma in
      accordance with the recent AJCC classification 2009: Review of the literature and
      recommendations for general practice].

PMID- 21884413
TI  - Typically atypical: histiocytoid Sweet syndrome, associated with malignancy.
AB  - Sweet syndrome (acute febrile neutrophilic dermatosis) is characterized by a
      dramatic onset of high fever, neutrophilia and typical skin lesions. About 20 %
      of patients have an associated malignancy, most commonly hematologic diseases.
      Chronic and paucisymptomatic manifestations of Sweet syndrome may be misdiagnosed
      or misinterpreted as harmless, resulting in delayed diagnosis. "Atypical"
      manifestations are especially suspicious for associated malignancies. This is
      demonstrated by a 39-year old patient with chronic and afebrile disease who was
      referred to our clinic only after symptoms had persisted for several months. By
      that point, an underlying nodular lymphocyte predominant Hodgkin's lymphoma had
      already reached an advanced stage. Skin biopsies revealed dermal infiltrates of
      histiocytoid cells of myelogenous origin, supporting a diagnosis of histiocytoid
      Sweet syndrome. Specific cutaneous infiltrates associated with myelogenous
      leukemia were ruled out.

PMID- 21884419
TI  - [A liver transplant patient with chronic erosive and scarring lesions on the
      scalp].

PMID- 21884424
TI  - Staying stagnant means falling behind.

PMID- 21884425
TI  - Ectopic reservoir placement--no longer in the space of Retzius.

PMID- 21884427
TI  - 2011 Sandra Leiblum presidential address.

PMID- 21884428
TI  - Women's Initiative on Sexual Health (WISH) position statement.

PMID- 21884431
TI  - Coincidence of GIST and pancreatic endocrine neoplasm in neurofibromatosis.
AB  - Carcinoids of the ampulla of Vater are infrequent tumors of which a quarter of
      cases have been detected in patients with type I neurofibromatosis. This
      hereditary disease is also associated with gastrointestinal stromal tumors
      (GIST). However, the coincidence of these three entities together have only been
      formerly detected in five cases. A 53 year-old female patient, diagnosed with
      type I neurofibromatosis, with a malignant carcinoid of ampulla of Vater and
      multiple gastrointestinal stromal tumors in the duodenum and jejunum, was treated
      with total pancreatectomy and the excision of her intestinal tumors. Five-years
      on, a follow-up showed the patient to be well, and free from tumor recurrence.
      The coexistence of an ampullary carcinoid tumor, GIST and neurofibramatosis is
      very rare. Radical curative surgical resection is a good treatment option, but
      the optimal management of this is not yet well established.

PMID- 21884432
TI  - The role of poly adenosine diphosphate ribose polymerase inhibitors in breast and
      ovarian cancer: current status and future directions.
AB  - Poly adenosine diphosphate ribose polymerase (PARP) inhibitors have demonstrated
      single agent activity in the treatment of patients with recurrent BRCA1-mutated
      and BRCA2-mutated breast and ovarian cancers. They also appear to have a
      potential role as maintenance therapy following chemotherapy in patients with
      platinum sensitive recurrent sporadic and BRCA1/2 related high-grade serous
      ovarian cancers. The concept of BRCAness raises the possibility that PARP
      inhibitors may be active in selected patients with homologous recombination (HR)
      DNA repair-deficient tumors, even if they do not harbor a BRCA1/2 germline
      mutation. Further research will be required to identify the subset of patients
      with sporadic cancers who may benefit from PARP inhibitor therapy. Precise
      details on the mechanisms of action, relative potency and anti-cancer effects of
      different PARP inhibitors remain to be clarified and are being investigated. PARP
      inhibitors are known to inhibit the base excision repair (BER) pathway but in
      addition, recent reports indicate that aberrant activation of the error-prone non
      homologous end-joining (NHEJ) pathway occurs in HR-deficient cells and that cell
      death provoked by PARP inhibition is dependent on NHEJ-induced genomic
      instability. Characterization of the precise molecular mechanisms responsible for
      PARP inhibitor activity should lead to the identification of predictive
      biomarkers of response and help identify which patients should be treated with
      PARP inhibitors. This is a very active field of research and the current status
      and future directions are reviewed.

PMID- 21884433
TI  - Second-line therapy for castrate-resistant prostate cancer: a literature review.
AB  - Despite a survival benefit in the first-line treatment of castrate-resistant
      prostate cancer (CRPC) with docetaxel, the prognosis remains limited. There are
      increasing options available for patients with CRPC in the second-line setting,
      but there is currently little consensus regarding the optimal treatment. There
      have been numerous phase II and retrospective studies examining second-line
      options in CRPC, including retreatment with docetaxel, mitoxantrone,
      cyclophosphamide and carboplatin, which can be associated with meaningful
      responses in a significant minority of patients. In 2010 three randomized trials
      were published or presented which demonstrated a survival benefit in the second
      line setting. These included cabazitaxel compared with mitoxantrone, sipuleucel-T
      (immunotherapy) and abiraterone acetate versus placebo. Ongoing research in the
      second-line setting of CRPC to optimize treatment options, with the objectives of
      survival prolongation, improvement in quality of life and pain management, is
      still needed.

PMID- 21884434
TI  - Targeted therapies in the treatment of gastric cancer.
AB  - Gastric cancer (GC) constitutes a major cause of cancer deaths worldwide. Recent
      improvements in both surgical techniques and adjuvant and neoadjuvant
      radiotherapy and chemotherapy approaches have increased the survival of patients
      with loco-regional disease. However most patients with GC have advanced disease
      either at diagnosis or at follow up. Despite recent advances in the treatment of
      advanced disease, these patients still have poor outcomes. An emerging
      understanding of the molecular pathways that characterize cell growth, cell
      cycle, apoptosis, angiogenesis and invasion has provided novel targets in cancer
      therapy. In this review we describe the current status of targeted therapies in
      the treatment of GC. These therapeutic strategies include epidermal growth factor
      receptor inhibitors, antiangiogenic agents, cell cycle inhibitors, apoptosis,
      promoters and matrix metalloproteinases inhibitors.

PMID- 21884435
TI  - The emerging era of personalized therapy in squamous cell carcinoma of the head
      and neck.
AB  - Over the past three decades there has been a move toward organ preservation
      protocols in the management of locally advanced mucosal head and neck squamous
      cell carcinomas (LAHNSCC) with combinations of radiotherapy (RT), chemotherapy
      and, more recently, biological agents. Current standard chemoradiation strategies
      have reached the upper limits of toxicity. In addition, the traditional one size
      fits all approach of grouping patients according to traditional
      clinicopathological features fails to take into account the vast underlying
      biological heterogeneity of tumors and their host. A number of recent advances
      such as highly conformal RT, molecular profiling and targeted agents, and
      improvements in treatment response assessment have set the scene for a
      fundamental paradigm shift toward greater tailoring of therapy with the aim of
      improving outcomes and reducing the burden of survivorship. This review focuses
      on the recognition of the prognostic value of tumor human papillomavirus (HPV)
      status, the incorporation of biologically targeted therapies and the evolving
      role of molecular imaging in predicting tumor response and prognosis in the
      curative management of LAHNSCC.

PMID- 21884436
TI  - Small cell lung cancer: patterns of care and their influence on survival - 25
      years experience of a single Australian oncology unit.
AB  - AIM: Evidence supporting improved outcomes for small cell lung cancer (SCLC) in
      recent decades is limited. This study aimed to identify patterns of care and
      survival over two time periods; 1 January 1987 to 31 December 1996 (cohort A) and
      1 January 1997 to 31 December 2006 9 (cohort B). METHODS: Patients'
      characteristics, management and outcome data were extracted from the Hospital
      Cancer Registry and clinical records. Survival analysis was determined using the
      Kaplan-Meier method and the log-rank test. Factors influencing survival outcome
      were assessed using Cox proportional hazards regression. RESULTS: The total
      number of patients was 392 (224 in cohort A, 168 in cohort B). Overall 38%
      patients in cohort A and 24% in cohort B had limited stage (LS) disease at
      diagnosis. Combined chemoradiotherapy for LS increased from 5% in cohort A to 65%
      in cohort B. Overall 19% of patients in cohort A and 24% in cohort B received
      symptomatic treatment alone (STA). Median survival for LS in cohort B was
      significantly higher (19.5 months), than in cohort A (11.8 months) (P = 0.03). In
      extensive stage (ES) disease, median survival was 6.2 months in cohort A and 4.3
      months in cohort B (P = 0.7). Variables for poorer outcome were STA, male gender,
      poor performance status, ES and whether the diagnosis was made in the earlier
      time period in cohort A. CONCLUSION: Outcomes for LS SCLC have improved with
      combined chemoradiotherapy, in keeping with worldwide data. The trends may also
      reflect recent improvements in staging and standardization of treatment. The
      outcome for ES-SCLC remains poor.

PMID- 21884437
TI  - Treatment of recurrent hepatocellular carcinoma after liver transplantation.
AB  - AIM: Liver transplantation (LT) is a curative treatment for localized
      hepatocellular carcinoma (HCC), but the recurrence rate after LT is about 10-20%,
      with a dismal prognosis. Little data exist as to the natural history, treatment
      outcome and optimal treatment of recurrent HCC after LT. We reviewed various
      treatment modalities given to patients with recurrent HCC after LT. METHODS:
      Among 132 patients who underwent LT for localized HCC, we retrospectively
      reviewed medical records of 39 of the 132 patients who developed recurrent HCC
      after LT. We analyzed the clinical outcome of various treatment modalities and
      treatment-related adverse events. RESULTS: A total of 39 (29%) of the original
      132 patients had recurrent HCC, most recurrences (82%) having occurred within 1
      year after LT and involved extrahepatic lesions. Only seven patients had
      recurrent disease limited to the liver. The median overall survival from the
      initial treatment of all relapsed patients was 6.9 months. There were various
      initial treatment modalities, namely palliative systemic chemotherapy, trans
      catheter arterial chemo-embolization/infusion (TACE/I), radiation therapy (RT),
      surgical resection and no treatment. The median overall survival was 9.5 months
      for first-line chemotherapy, including those who had prior local therapy, 6.3
      months TACE/I and 6.9 months for RT. CONCLUSION: Various clinical approaches have
      been used to treat patients with recurrent HCC after LT in a clinical setting.
      More effective strategies and clinical guidelines for recurrent HCC following LT
      must be established.

PMID- 21884438
TI  - Clinical analysis of Chinese limb osteosarcoma patients treated by two
      combinations of methotrexate, cisplatin, doxorubicin and ifosfamide.
AB  - AIMS: The objective of this study was to investigate the efficacy and toxic side
      effects of two combinations of methotrexate, cisplatin, doxorubicin and
      ifosfamide on treating Chinese osteosarcoma patients. METHODS: A retrospective
      analysis was conducted of 185 osteosarcoma patients treated with the four drugs
      mentioned above. A total of 93 patients received the Italian therapeutic
      treatment (IOR-OS/N-5: Instituto Ortopedic Rizzoli-Section of
      Osteosacorma/Neoadjuvant chemotherapy-5) and the remaining 92 patients received
      the therapeutic treatment optimized by our department. We compared the efficacy
      and toxic side effects of these two therapies. RESULTS: The limb salvage rates, 3
      year recurrence rates and 3-year metastasis rates of IOR-OS/N-5 and our optimized
      treatment were 52.7 and 58.7%; 20.9 and 11.4% and 44.1 and 27.2%, respectively.
      The 3-year survival rates and the 3-year disease-free survival rates of IOR-OS/N
      5 and our optimized treatments were 62.4 and 78.4%; and 53.6 and 67.8%,
      respectively. Overall survival and disease-free survival rates were significantly
      different between these two treatments (P = 0.032 and 0.024, respectively). Liver
      function with degree III and IV damage accounted for 35.2 and 16.6% of the total
      adverse reactions in the IOR-OS/N-5 and our optimized treatment groups,
      respectively. Degree III-IV neutropenia accounted for 22.6 and 40.0%,
      respectively, in the IOR-OS/N-5 and optimized treatments. CONCLUSION: The
      optimization of MTX, DDP, DOX and IFO based on Chinese patients' physiology
      increased the tolerance and efficacy for the treatment of osteosarcoma.

PMID- 21884439
TI  - Exploratory analysis of cardiac biomarkers in women with normal cardiac function
      receiving trastuzumab for breast cancer.
AB  - AIM: As there is no method to detect trastuzumab-related cardiotoxicity (TRC)
      preclinically, patients are monitored with serial assessments of left ventricular
      ejection fraction (LVEF) with instigation of cardiac therapy and possible
      interruption of trastuzumab therapy if TRC develops. Serum cardiac biomarkers,
      including troponins and natriuretic peptides, represent possible tools to detect
      cardiotoxicity at a preclinical level. METHODS: We sought biochemical evidence of
      cardiac damage or strain in a cohort of women already receiving trastuzumab by
      performing a cross-sectional study of serum cardiac biomarkers. All patients had
      a normal LVEF and no clinical evidence of cardiac failure. Serum troponin I and N
      terminal pro-B type natriuretic peptide (NT pro-BNP) were assayed immediately
      prior to trastuzumab infusion (t0; n = 36) and 24 hours later (t24; n = 31).
      RESULTS: Troponin I was not elevated in any patient at t0 or t24. Overall 14/36
      (39%) patients had at least one NT pro-BNP level above the upper limit of normal
      (ULN) and both levels were above the ULN in 8/31 (26%) patients. There was no
      significant change in NT pro-BNP from t0 to t24. CONCLUSION: NT pro-BNP levels
      are elevated in a significant proportion of patients with normal LVEF receiving
      trastuzumab. Troponin I levels are not raised in this group, perhaps reflecting
      the mechanism of cardiotoxicity. The data provide biochemical evidence of
      subclinical cardiac strain in women receiving trastuzumab. Results are
      exploratory and have informed the design of a larger study examining the
      predictive utility of serial serum NT pro-BNP levels for TRC in the adjuvant
      setting.

PMID- 21884440
TI  - Very high GFR in cancer patients undergoing chemotherapy: prevalence, carboplatin
      dosing patterns and chemotherapy toxicity.
AB  - AIM: Carboplatin dosing depends on accurate glomerular filtration rate (GFR)
      estimation. There is a lack of clinical agreement about carboplatin dosing when
      the GFR measurement is very high (>110 mL/min). METHODS: A retrospective audit of
      pre-chemotherapy 99m technetium (Tc) diethylenetriamene pentaacetate (DTPA)
      radionuclide GFR estimations and patients' chart review were performed from
      January 2006 to May 2009. The primary objective was to determine the prevalence
      of patients with a high GFR and the incidence of myelotoxicity in this group.
      RESULTS: Overall 18 of 148 treated patients (14%) measured GFR >110mL/min. The
      GFR values of six of the 18 patients were capped for dose calculation. In eight
      patients a measured GFR corrected for body surface area was used and in four the
      actual measured GFR was used for dose calculation. In total, 63 cycles of
      chemotherapy were delivered. Grade III or IV myelotoxicity accounted for 37%
      (15/41) of all myelotoxicities. Neutropenia accounted for almost 39% of all
      myelotoxicities (16/41). Two patients (11%) were hospitalized due to febrile
      neutropenia. Eight patients (40%) had dose reduction and four (20%) had treatment
      delays due to myelotoxicity. The frequency of myelotoxicity was high irrespective
      of the GFR used (corrected or uncorrected) in calculating the chemotherapy dose.
      CONCLUSION: High values of GFR, by 99mTc DTPA radionuclide measurement, are a
      common finding in pre-chemotherapy patients irrespective of age. Carboplatin
      dosing patterns in this group of patients vary among treating oncologists and a
      standardized approach is needed.

PMID- 21884441
TI  - Efficacy and tolerability of weekly low-dose cisplatin concurrent with
      radiotherapy in head and neck cancer patients.
AB  - AIMS: In this retrospective analysis, we describe the efficacy and tolerability
      of weekly cisplatin 40 mg/m(2) used in concurrent chemoradiation of head and neck
      cancer at the Townsville Cancer Centre. METHODS: Review of medical records of
      patients who received radical chemoradiotherapy for head and neck cancer at
      Townsville Cancer Centre from 2003 to 2009. RESULTS: In all 102 patients were
      analysed, 62 of whom had definitive chemoradiation and the remainder adjuvant
      chemoradiotherapy. Median follow up was 20.1 months (range 5-86 months). Overall
      68.6% of patients received 5 weeks or more of planned chemotherapy. Radiotherapy
      interruptions occurred in four (6.4%) patients. The rate of grade 3-4 adverse
      events was 51% including neutropenia (18.6%), mucositis (21.8%) and dysphagia
      (12.9%) and 30.7% of patients needed hospital admission to manage toxicities. For
      definitive and adjuvant groups, estimated 3-year survival was 64.5 and 71.5%,
      respectively, and estimated 3-year disease-specific survival rates were 70.3 and
      81.6%, respectively. The 3-year overall survival for patients who received five
      or more cycles of chemotherapy was 75.2%, compared to 52.6% for those receiving
      fewer than five cycles (P = 0.018). CONCLUSION: Despite this is being a small
      retrospective study, survival figures and toxicity profiles of low dose weekly
      cisplatin are comparable to historical controls using high-dose regimens, hence
      justifying our approach. In addition, radiotherapy interruptions are minimized
      and cisplatin is easy to administer in outpatient settings. Future three-arm
      studies could include this regimen as the basis of treatment combined with
      targeted therapies.

PMID- 21884442
TI  - Gastroenteropancreatic neuroendocrine tumors: incidence and treatment outcome in
      a single institution in Korea.
AB  - AIM: We studied to identify the clinicopathological features, treatment outcome,
      and prognostic factors for patients with gastrointestinal and
      hepatopancreaticobiliary neuroendocrine tumor (NET). METHOD: Between February
      2001 and May 2006, a total of 470 patients were diagnosed with NET arising from
      the gastrointestinal tract, pancreas, and hepatobiliary system. The retrospective
      patient cohort was obtained and analyzed. RESULTS: The male to female ratio was
      1.5:1, and the median age was 55 years (range, 16-81). The most common primary
      site was the rectum (55.8%). Overall 29 (6.2%) originated from the hepatobiliary
      system. At initial presentation, 60 patients (12.8%) showed distant metastases.
      Curative surgery or endoscopic resection was performed in 401 patients.
      Histopathological distributions were as follows: well differentiated tumor
      (82.1%), well differentiated carcinoma (10.2%) and poorly differentiated
      carcinoma (7.7%). The frequency of the poorly differentiated type was somewhat
      higher in the hepatobiliary system than in the pancreas and gastrointestinal
      tract (44.8, 15.4 and 2.8%, respectively, P < 0.05). The estimated 5-year overall
      survival rate for all patients was 89.6%. Multivariate analysis showed that
      distant metastases (P = 0.018), origin from the hepatobiliary system (P < 0.001)
      and poorly differentiated neuroendocrine carcinoma (P < 0.001) were independent
      predictors for poor survival outcome. CONCLUSION: Patients with locoregional NET
      had a favorable long-term survival after curative resection. Distant metastases,
      hepatobiliary localization and a poor degree of tumor cell differentiation were
      poor prognostic factors. Further investigational approaches for treatment of
      advanced disease are needed.

PMID- 21884443
TI  - Exploring consent to randomized placebo-controlled clinical trials in oncology.
AB  - AIMS: Randomized placebo-controlled trials are critical for advancing knowledge
      in oncology, yet little is known about optimal communication for informed
      consent. This study aimed to identify patient preferences for and satisfaction
      with three consultation styles (information-focused, emotion-focused and
      collaborative) in simulated discussions of four clinical trial concepts
      (randomization, placebo, tissue analysis and oncologists' recommendation).
      METHODS: In total 75 Australian cancer patients and carers, or both, viewed
      videotaped simulated consultations with a doctor and patient discussing a
      randomized, placebo-controlled trial. Their satisfaction and preferences for both
      consultation style and information were assessed. The patients' characteristics
      and decision-making preferences were also evaluated as potential predictors for
      consultation style preference. RESULTS: Participants preferred a collaborative
      consultation style when discussing randomization (74.6%), placebo (71.4%) and
      oncologist's recommendation (77%). However an emotion-focused consultation style
      was preferred when discussing tissue analysis (81%). The participants represented
      a highly information-seeking group, although most favoured collaborative or
      passive roles in treatment decision-making. Limited variables were identified
      that predict consultation style preference. CONCLUSION: While supporting the
      value of a collaborative approach to clinical trial communications, the study
      finding that tissue analysis requires a more emotion-focused approach highlights
      a new focus for trial communication and confirms the need for doctors to remain
      flexible in their consultation style.

PMID- 21884444
TI  - Predictive factors for detecting malignancy in central and lateral cervical lymph
      nodes in papillary carcinoma of the thyroid.
AB  - AIM: To determine the factors for predicting malignant diagnosis and limitations
      in ultrasonography guided fine-needle aspiration cytology of central and lateral
      cervical lymph nodes in patients with primary differentiated thyroid papillary
      carcinoma. METHODS: Biopsies of cervical lymph nodes were performed in 120
      patients, 31 of whom had subsequent surgical diagnoses. Factors examined were
      patient's age and gender of the patients, location (central and lateral
      compartments), hypoechogenicity with loss of hilum, microcalcification, cystic
      feature, minimum and maximum diameters and index value (minimum/maximum
      diameter). RESULTS: The mean minimum diameter and index value of the lymph nodes
      were 9.9 +/- 4.9 mm and 0.60 +/- 0.19, respectively. Microcalcifications and
      cystic parts were specific findings with rates of 93.9% and 95.1%, respectively.
      Microcalcification, cystic feature, minimum diameter and index value were poor
      predictors of malignancy. The predictors were central location (P = 0.031) and
      hypoechogenicity with loss of hilum in lateral neck (P = 0.019). Central nodes
      led to a major problem for biopsy success due to postoperative changes and
      anatomic position. Nondiagnostic (30%) nodes were therefore mostly central.
      CONCLUSION: The involvement of the central neck should be a major indication of
      lymph node biopsy and pathological diagnosis regardless of the imaging findings.
      In the lateral compartment, hypoechogenicity with loss of hilum,
      microcalcifications, cystic parts and an index value >= 0.51 are indications of a
      lymph node biopsy to rule out malignancy.

PMID- 21884445
TI  - Transient efficacy of cord blood transplantation in acute myeloid leukemia with
      t(16;21)(p11;q22).

PMID- 21884446
TI  - What constitutes a multidisciplinary team meeting?

PMID- 21884448
TI  - Care Pathways as a means to implement evidence in daily practice.

PMID- 21884449
TI  - Nurse-led clinics as an effective service for cardiac patients: results from a
      systematic review.
AB  - AIM: The article summarises results of a systematic review on the effectiveness
      of nurse-led clinics for patients with coronary heart disease. The objective was
      to present the best available evidence related to effective interventions in
      nurse-led cardiac clinics including patient education, risk factor assessment and
      continuity of care. METHODS: Following the principles of the Cochrane
      Collaboration for systematic reviews on effectiveness, this is an update to a
      previously published review. Thirty databases, relevant journals and hand
      searching of reference lists were the basis for a comprehensive literature search
      for the period September 2002 to March 2008. Assessment of methodological
      quality, data extraction and synthesis was undertaken using a systematic review
      management tool (JBI-SUMARI). When possible, data was pooled in a meta-analysis.
      RESULTS: The systematic review is based on seven randomised controlled trials.
      Inconsistencies of interventions executed in nurse-led clinics and various
      effects on the outcomes make a comparison difficult. The major nurse-led
      intervention applied in the clinics consisted of health education, counselling
      behaviour change and promotion of a healthy lifestyle. There were no harmful
      effects on patients with coronary heart disease identified when exposed to a
      nurse-led clinic. A few risk factors were significantly reduced in the short term
      by attending nurse-led clinics, but long-term changes were less apparent. The
      success of modifying behaviour such as smoking cessation and diet adherence was
      limited. However, nurse-led clinics may positively influence perceived quality of
      life and general health status. CONCLUSION: The results indicated that care was
      equivalent to non-nurse-managed clinics, and there was no greater risk of poorer
      outcomes in the nurse-led clinics. The effectiveness of clinics might be
      dependent on the intensity of the nursing support. Before establishing a nurse
      led clinic appropriate qualification and responsibilities, as well as the
      particular structure of the healthcare system and funding possibilities have to
      be considered. The combination of counselling and regular assessment of risk
      factors and health status delivered at nurse-led clinics is supported by the
      available research, and given that outcomes were in general equivalent between
      nurse-led and other clinics, further research should investigate the cost
      effectiveness of the different models of care.

PMID- 21884450
TI  - Anxiety in women with breast cancer undergoing treatment: a systematic review.
AB  - BACKGROUND: Breast cancer is one of the most common cancers worldwide, and
      anxiety is a psychological morbidity that is inevitable. Many researchers have
      investigated the prevalence and detrimental effects of anxiety in breast cancer
      treatment, but little is known about differences in anxiety level among women
      receiving different breast cancer treatments. A systematic review of all
      available literature was needed to attain better understanding of anxiety in
      patients undergoing treatment for breast cancer. AIM: This review aimed to
      determine the best available evidence on the level of anxiety among women with
      breast cancer who were undergoing cancer treatment(s), and the factor(s)
      contributing to anxiety in various treatment modalities. METHODS: The search
      sought to gather data from published and unpublished studies conducted between
      1990 and 2010. An initial search on CINAHL and Medline was done to identify
      relevant search terms. A search strategy was then developed, using MeSH headings
      and key words. The following databases were searched: CINAHL, PubMed,
      ScienceDirect, PsycINFO, Cochrane Database of Systematic Review, Scopus, Wiley
      InterScience and PsycARTICLES. All papers are quantitative papers (randomised
      controlled trials and descriptive studies) that examined anxiety level in women
      with breast cancer of stage 0 to stage IIIA, over and equal to 21 and below 65
      years of age, who were undergoing/had undergone treatment restricted to
      chemotherapy, radiotherapy and/or surgery, and these quantitative papers have
      made correlations between women's anxiety levels and contributing factors. The
      Hospital Anxiety and Depression Scale and State-Trait Anxiety Inventory were the
      two tools most frequently used by these papers to quantify the anxiety level. Two
      reviewers independently assessed the eligibility of the papers for inclusion.
      Eighteen papers were selected based on relevance, and assessed for methodological
      quality using MAStARI. Ten research papers that met our methodological standard
      were included in the review. Both reviewers agreed on the papers to be included
      and excluded. Due to the methodological heterogeneity of the included papers, a
      meta-analysis was not possible. The studies were hence presented in narrative
      summary. RESULTS: Anxiety seems to be ubiquitous, presenting itself in all
      treatment types for breast cancer. Anxiety level in women who underwent
      chemotherapy was highest before the first chemotherapy infusion, mediated by age
      and trait anxiety. Radiotherapy regimes did not affect anxiety level in
      radiotherapy-treated patients, and most research concluded that anxiety level was
      higher among women who underwent mastectomy than those who underwent breast
      conservation therapy. CONCLUSIONS: The prevalence and intensity of anxiety have
      been shown to be pronounced among breast cancer women who were undergoing/had
      undergone one or more of the three treatments. Chemotherapy, as compared to other
      treatments, is shown to be associated with a higher anxiety level. With the
      prevalence, intensity and correlated factors of anxiety identified through this
      review, future research may investigate the interventions that could help
      alleviate anxiety among these patients. Anxiety is prevalent in women with breast
      cancer undergoing treatment, especially those undergoing chemotherapy. Healthcare
      professionals should pay greater attention to identify signs of anxiety in
      patients and design interventions to help alleviate it earlier.

PMID- 21884451
TI  - A systematic review of the effectiveness of primary health education or
      intervention programs in improving rural women's knowledge of heart disease risk
      factors and changing lifestyle behaviours.
AB  - BACKGROUND: Cardiovascular disease is the leading cause of death and disability
      for women in Australia. Women living in rural areas are at greater risk of heart
      disease, because of limited access and availability of healthcare in rural areas.
      Lifestyle is a major determinant to the risk of heart disease. Risk factors such
      as smoking, hypertension, diet, physical activity and alcohol intake can be
      controlled or modified by lifestyle changes. As heart disease develops over many
      years, women need to be following healthy lifestyle practices and reduce their
      chance of a first or recurrent heart attack. AIM: To determine the effectiveness
      of primary health education or intervention programs for cardiac risk reduction
      in healthy women living in rural areas. INCLUSION CRITERIA: Types of
      participants. Women aged 16-65 years, living in rural areas, who participated in
      primary healthcare education programs. Types of interventions. Primary health
      education or intervention programs aimed at improving rural women's knowledge of
      their risk of heart disease, for example group work, videos, telephone,
      workshops, educational material and counselling. Types of outcomes. Primary
      outcomes included: * Knowledge level of heart disease risk factors. * Lifestyle
      modification, for example dietary improvements such as reduced daily salt intake,
      increased intake of fruit and vegetables and decreased intake of fat, increased
      frequency of exercise, decreased levels of smoking, alcohol intake within
      national guidelines. * Health assessment measures, for example blood pressure,
      body weight, cholesterol levels. Types of studies. Any randomised controlled
      trials, other experimental studies, as well as cohort, case-control and cross
      sectional studies were considered for inclusion. Search strategy. A search for
      published and unpublished studies in the English language was undertaken.
      METHODOLOGICAL QUALITY: Each study was appraised independently by two reviewers
      using the standard Joanna Briggs Institute instruments. DATA COLLECTION AND
      ANALYSIS: Information was extracted from studies meeting quality criteria using
      the standard Joanna Briggs Institute tools. Although similar outcomes are
      explored in many of the studies, the variable outcome measures precluded the use
      of meta-analysis. Data are therefore summarised in tables or by using narrative
      analysis. RESULTS: Nine trials were included in the review. Three trials compared
      the effects of interventions on physical activity, one on smoking and five on
      multiple risk factors. Studies following interventions targeting physical
      activity reported that women's physical activity can be increased and that these
      increases can be sustained at 12 months. While there were decreases in blood
      pressure at 6 months, studies with a 5-year follow up found no decreases for both
      systolic and diastolic blood pressure. Overall results of studies into dietary
      modification programs also did not sustain an effect over a longer period of
      time. CONCLUSION: The results of this review suggest that in rural areas,
      lifestyle interventions delivered by primary care providers in primary care
      settings to patients at low risk appeared to be of marginal benefit. Resources
      and time in primary care might be better spent on patients at higher risk of
      cardiovascular disease, such as those with diabetes or existing heart disease.

PMID- 21884452
TI  - Rural and remote Australian general practice nurses' sources of evidence for
      knowledge translation: a cross-sectional survey.
AB  - PURPOSE: This paper explores nurses' sources of knowledge for evidence-based
      practice, comparing rural/remote, urban and regional participants. METHODS: A
      cross-sectional survey of practice nurses in the state of Victoria was conducted
      in 2008. The instrument used was the Developing Evidence-based Practice
      Questionnaire - Au, distributed to a convenience sample of nurses with response
      of 590 (33%). Survey data were stratified by geographical location for this
      exploratory report. RESULTS: The sample was representative of practice nurses,
      with half employed in either regional or rural and remote areas. Rural and remote
      nurses were less qualified in nursing than urban nurses. However, rural, remote
      and regional nurses were significantly less likely to apply experiential
      knowledge as evidence and were more likely to source knowledge from clinical
      nurse specialists or nurse practitioners, local audit reports or articles in
      research and medical journals. Nurses in each work category reported in-service
      training, conferences and information shared by colleagues as important in
      developing their knowledge for practice. According to participants, evidence
      based practice would be promoted by allocation of work time, education and
      training in research skills, and improved access to resources. CONCLUSIONS: Rural
      and remote practice nurses prioritised the development of their skills in
      sourcing and appraising evidence for practice as a strategy to facilitate
      knowledge translation at the point of care.

PMID- 21884453
TI  - Evaluating the role and value of a national office to coordinate Liverpool Care
      Pathway implementation in New Zealand.
AB  - BACKGROUND: New Zealand is one of 20 countries implementing the Liverpool Care
      Pathway for the Dying Patient (LCP) to improve quality care of the dying. The LCP
      is an integrated care pathway that guides healthcare professionals to deliver
      evidence-based, best practice care to dying patients and their families in the
      last days and hours of life, irrespective of diagnosis or care setting. Currently
      the LCP Central Team coordinates LCP implementation and dissemination for all
      international collaborating countries except New Zealand, from its base in
      Liverpool in the UK. With the support of the LCP Central Team, New Zealand is the
      first country to establish a National Office to assume the responsibility for
      promoting the sustainable implementation of the LCP within its own borders and
      context of end-of-life care. AIMS: To evaluate the role and value of a New
      Zealand National LCP Office (NZ LCP Office) from the perspective of key
      stakeholders. METHODS: A mixed methods approach was applied, which intentionally
      combined two different survey methods in sequence. In Phase 1, key stakeholders
      (n = 28) were interviewed to explore their perspectives for the role and value of
      the NZ LCP Office. Findings from Phase 1 informed an online questionnaire
      distributed to a larger group of key stakeholders (n = 36, 62% response rate) in
      Phase 2. RESULTS: When considering the role of the NZ LCP Office, key
      stakeholders identified two core services as highly important, namely the
      promotion of the sustainable implementation of LCP and the provision of a
      national LCP information network. Other key initiatives identified by key
      stakeholders as important included the NZ LCP Office continuing to work in
      consultation and collaboration with the LCP Central Team and to be a voice for
      end-of-life care issues in New Zealand. The value or benefit of the NZ LCP Office
      was endorsed, in that service performance was rated as good or very good by at
      least 90% of the respondents, plus 40% of participants perceived the NZ LCP
      Office had contributed to positive changes in LCP document compliance, program
      integrity and improvement in care of the dying to a moderate extent. CONCLUSION:
      Having a National LCP Office in New Zealand to coordinate sustainable LCP
      implementation and maintain the integrity of the LCP program within the context
      of the country's own healthcare system was seen as crucial by key stakeholders.

PMID- 21884454
TI  - Intra-articular hyaluronic acid preparations for use in the treatment of
      osteoarthritis.
AB  - Intra-articular hyaluronic acid preparations have been available for the
      treatment of osteoarthritis of the knee for over 15 years. Their use has been
      limited by cost, difficulties of administration and conflicting evidence of
      efficacy. Difficulties in conducting adequate clinical trials have resulted in
      the appearance of multiple meta-analyses whose findings are not congruent. The
      appearance of a single injection agent and a better understanding of the
      mechanisms by which this intervention is effective may help to solve this ongoing
      problem in healthcare research.

PMID- 21884455
TI  - Evidence-based medicine: UK doctors' attitudes and understanding.
AB  - The aim of this paper is to understand UK doctors' attitudes towards evidence
      based medicine (EBM) and their self-perceived understanding of specified EBM
      terms. An online questionnaire was emailed to doctor's emails (identified from
      the Internet) and the questionnaire URL was promoted on certain websites and
      electronic newsletters. This article focuses on the EBM questions posed on this
      research instrument. Respondents were generally positive towards the practice of
      EBM; for example, 72.3% of UK doctors agreed that EBM improves patient outcomes.
      Over 85% of respondents were either able to explain (or had some understanding)
      all the specified EBM terms. Respondents who had graduated from medical school
      most recently were more positive towards EBM and had a stronger self-perceived
      understanding of the EBM terms. This research found that doctors were generally
      in favour of EBM and their understanding of specialist terms was higher than
      previous published research.

PMID- 21884467
TI  - Serum TNF-related and weak inducer of apoptosis levels in septic shock patients.
AB  - Capillary permeability is a tightly regulated feature of microcirculation in all
      organ beds. In sepsis, this feature is fundamentally altered. We have previously
      reported elevated levels of angiopoietin-2 in patients with septic shock, and
      have investigated tumor necrosis factor (TNF)-related and weak inducer of
      apoptosis (TWEAK), which mediates both angiogenesis and inflammation, in those
      patients. Enzyme-linked immunoassay was used to measure serum TWEAK levels in 20
      patients with septic shock, all of whom were treated by direct hemoperfusion with
      a polymyxin B-immobilized fiber column (DHP-PMX), and in 20 non-septic controls.
      The TWEAK levels were higher in patients with septic shock (192.8 +/- 230.5
      pg/mL) than in controls (84.1 +/- 28.7 pg/mL, P = 0.043). Between 11 survivors
      and 10 non-survivors, there was no significant difference in the serum TWEAK
      levels before the DHP-PMX therapy. During DHP-PMX therapy, however, the serum
      TWEAK levels were significantly increased in non-survivors (142.2 +/- 88.1 pg/mL
      to 399.0 +/- 307.1 pg/mL, P = 0.022). There was a significant correlation between
      the serum TWEAK levels and white blood cell counts (r = 0.393, P < 0.001),
      platelet counts (r = 0.418, P < 0.001), or serum CRP levels (r = 0.259, P =
      0.029), but there was no correlation between the serum TWEAK levels and blood
      pressure. The serum TWEAK levels were also correlated with the ratio of
      angiopoietin-2 to -1 (r = 0.464, P < 0.001). TWEAK may be a suitable marker of
      disease severity and mortality in septic patients, and TWEAK levels may be
      associated with vascular permeability via angiopoietin balance.

PMID- 21884468
TI  - Angiopoietin balance in septic shock patients with acute lung injury: effect of
      direct hemoperfusion with polymyxin B-immobilized fiber.
AB  - Acute lung injury (ALI) in sepsis is characterized by an increase in
      microvascular permeability, resulting in pulmonary edema. Several studies have
      suggested that angiopoietin-1 and -2 play a contributory role in the pathogenesis
      of ALI. Polymyxin B-immobilized fiber column hemoperfusion is effective for
      sepsis-induced ALI. We investigated the angiopoietin levels before and after
      direct hemoperfusion with polymyxin B-immobilized fiber column (PMX) therapy.
      Enzyme-linked immunoassay was used to measure the serum angiopoietin-1 and -2
      levels in 25 patients with septic shock treated with PMX. Eleven of the 25
      patients were diagnosed with ALI. There was a significant positive correlation
      between the angiopoietin-1 level and the PaO(2) /FiO(2) ratio, but there was a
      significant inverse correlation between the angiopoietin-2 level and the PaO(2)
      /FiO(2) ratio. The mean angiopoietin-1 level before PMX therapy in the ALI group
      was significantly lower and the mean angiopoietin-2 level was significantly
      higher than in the non-ALI group. The mean angiopoietin-1 level of the ALI
      patients in response to PMX therapy was increased during PMX therapy, but that of
      the non-ALI patients with newly occurring ALI showed a decreased angiopoietin-1
      level. On the other hand, the mean angiopoietin-2 level of the responders was
      decreased during PMX therapy, but that of patients with newly occurring ALI
      showed an increased angiopoietin-2 level. This result suggested that each
      angiopoietin-1 and -2 level may play a role in the pathogenesis of ALI and that
      PMX therapy ameliorates the angiopoietin balance in patients with ALI in sepsis.

PMID- 21884469
TI  - Effect of various anticoagulant agents on large-volume leukocytapheresis using
      new Cellsorba CS-180S Filter.
AB  - We conducted a study to evaluate the effect of various anticoagulant agents on
      large-volume leukocytapheresis using the new Cellsorba CS-180S Filter filled with
      a changed solution of sodium pyrosulfite and sodium carbonate. We conducted the
      study on a total of 12 cases of rheumatoid arthritis. As the anticoagulant agents
      we used sodium citrate, nafamostat mesilate and low molecular weight heparin. The
      new Cellsorba CS-180S was safely used with the various blood anticoagulant
      agents. Also, through adjustment of the sodium citrate percentage to the blood
      flow volume, it is hypothesized that it is possible to increase the neutrophil
      removal rate.

PMID- 21884470
TI  - Relevance of the processed blood volume per granulocyte and monocyte apheresis
      session to its clinical efficacy in patients with ulcerative colitis.
AB  - Granulocyte/monocyte adsorption (GMA) has been introduced as an adjunct
      intervention for active ulcerative colitis (UC) patients. The processed blood
      volume (PV) per GMA session is an important factor for its efficacy because
      depletion of elevated/activated myeloid leukocytes is its main action. Hitherto,
      this aspect of GMA has been largely ignored. Thirty-three patients were enrolled
      for remission induction therapy with five weekly GMA sessions at a standard PV of
      1800 mL, regardless of patients' bodyweight (BW). The patients were divided into
      three groups: high (H)BW (>= 65 kg, n = 11), 50 kg <= medium (M)BW < 65 kg (n =
      12), and low (L)BW (<= 50 kg, n = 10). UC clinical activity index (CAI) was
      according to Lichtiger, and the clinical efficacies were evaluated at both one
      week post 3(rd) GMA (Week 4) and one week post 5(th) GMA (Week 6). The average BW
      was 70.9 +/- 6.2 kg in HBW, 55.8 +/- 4.5 kg in MBW, and 46.8 +/- 1.2 kg in LBW,
      indicating the mean PV/BW in the three groups being 25.6 +/- 2.12, 32.5 +/- 2.50,
      and 38.7 +/- 1.0 (mL/kg, P < 0.05), respectively. The LBW group consisted of
      female patients only. Significant improvements of CAI were seen before treatment
      at either Week 4 or Week 6 in all groups. A significantly higher remission rate
      was achieved in the LBW (80.0%) vs. MBW (33.3%) or HBW (27.3%) at Week 6 (P <
      0.03). According to this GMA evaluation, the lower-limit of optimum PV/kg should
      be higher than 38.7 mL/kg for its potential clinical efficacy to be significantly
      greater than the routine GMA method. Additional BW-oriented GMA studies in larger
      and gender controlled cohorts of patients should strengthen our findings.

PMID- 21884471
TI  - Immunoregulatory effects of adsorptive granulocyte and monocyte apheresis in
      patients with drug refractory Crohn's disease.
AB  - In Japan, adsorptive granulocyte/monocyte apheresis (GMA) is an approved
      treatment option in patients with active Crohn's disease (CD). However, there is
      inadequate knowledge regarding the mechanism(s) of therapeutic effects of this
      non-pharmacologic treatment strategy. Further, recently we have been interested
      in the regulatory T-cell (Treg) profile which has an essential immunoregulatory
      function. Thirteen CD patients were treated with a single GMA session. The mean
      CD activity index (CDAI) and duration of CD were 218.5 and 9.8 years,
      respectively. Eight healthy volunteers participated as a control group. From CD
      patients, whole blood was taken immediately before and after the GMA session
      directly from the GMA column inflow and outflow lines. Broad spectrum serum key
      cytokines and chemokines were measured by suspension-array and ELISA. At
      baseline, almost all assayed inflammatory cytokines were significantly elevated
      in CD patients. Treg-associated cytokines including IL-10 (P < 0.02) and
      transforming growth factor (TGF)-beta1 (P < 0.03), were higher in the GMA column
      outflow vs. inflow. In contrast, the Th1/Th2 balance, defined as IFN-gamma/IL-10
      was lower during hemofiltration (P = 0.05), potentially due to an elevated IL-10
      (P < 0.02) because an elevation of pro-inflammatory IFN-gamma (Th1) was not
      observed at the GMA column outflow. A single GMA session had a significant impact
      on the Treg profile. Treg-related cytokines like IL-10 and TGF-beta1 in the blood
      returning to the patients from the GMA column outflow were elevated, while pro
      inflammatory cytokines like IFN-gamma were not. This action of GMA is potentially
      very interesting in patients with immune disorders, like CD patients.

PMID- 21884472
TI  - Generalized pustular psoriasis successfully treated with granulocyte and monocyte
      adsorption apheresis.
AB  - Generalized pustular psoriasis (GPP) is one of the neutrophilic dermatoses mainly
      caused by activated neutrophils and monocytes. Granulocyte and monocyte
      adsorption apheresis (GCAP) is a useful extracorporeal circulation therapy for
      removal of activated granulocytes and monocytes. In this study, GCAP was used to
      treat three patients with different types of GPP; the diagnoses indicated patient
      1 had GPP, patient 2 had GPP developed from psoriasis vulgaris and patient 3 had
      GPP based on psoriatic erythroderma. We performed GCAP on each of these patients
      once a week, for a total of five times. We found that the patients' pustules and
      edema disappeared and their erythema was reduced by GCAP therapy. Moreover, no
      adverse effects were observed. Thus, we conclude GCAP could be effective for
      treating various types of GPP.

PMID- 21884473
TI  - Evaluation of the effect of ulinastatin on the production of macrophage colony
      stimulating factor in vitro for potential combination therapy with leukocyte
      adsorption.
AB  - Macrophage colony-stimulating factor (M-CSF) induces normal intestinal
      macrophages that have anti-inflammatory effects. Thus, M-CSF-rich conditions in
      colonic tissues seem to contribute to the improvement of pathological conditions
      in patients with inflammatory bowel diseases (IBD). However, it has not been
      clarified whether current therapies for IBD, including granulocyte/monocyte
      adsorptive apheresis using an Adacolumn, and ulinastatin, a serine protease
      inhibitor, affect the production of M-CSF. To clarify the effects of these
      therapies on M-CSF production, we investigated whether monocyte adsorption to
      cellulose acetate (CA) beads (carriers for Adacolumn therapy) and ulinastatin
      augmented M-CSF production in in vitro experiments. Peripheral blood was
      incubated with and without CA beads, and then M-CSF production was measured.
      Additionally, peripheral blood containing serial dilutions of ulinastatin was
      incubated with CA beads followed by measurement of M-CSF production. Monocyte
      adsorption to CA beads did not affect M-CSF production. A high concentration of
      ulinastatin augmented M-CSF production without inhibiting monocyte adsorption to
      CA beads, although a low concentration of ulinastatin conversely suppressed M-CSF
      production. The present study found that a high concentration of ulinastatin,
      which was administrated with CA beads, increased the production of M-CSF. Our
      results suggest that a combination of ulinastatin and Adacolumn therapy may
      provide more clinical efficacy for the treatment of IBD in terms of the
      production of M-CSF.

PMID- 21884474
TI  - In vitro evaluation of high mobility group box 1 protein removal with various
      membranes for continuous hemofiltration.
AB  - The high mobility group box 1 protein (HMGB1) is an alarmin that plays an
      important role in sepsis and has been recognized as a promising target with a
      wide therapeutic window; however, no drugs and devices are currently in practical
      use. We hypothesized that hemofilters composed of porous membranes or cytokine
      adsorbing membranes could remove HMGB1 from the blood. We performed experimental
      hemofiltration in vitro using four types of hemofilters composed of different
      membranes specifically designed for continuous hemofiltration. The test solution
      was a 1000-mL substitution fluid containing 100 ug of HMGB1 and 35 g of bovine
      serum albumin. Experimental hemofiltration was conducted for 360 min in a closed
      loop circulation system. Among the four membranes, surface-treated
      polyacrylonitrile (AN69ST) showed the highest capacity to adsorb HMGB1; it
      adsorbed nearly 100 ug of HMGB1 in the initial 60 min and showed a markedly high
      clearance rate (60.8 +/- 5.0 mL/min) at 15 min. The polymethylmethacrylate
      membrane had half of the adsorption capacity of the AN69ST membrane. Although the
      highest sieving coefficient for HMGB1 was obtained with the high cut-off
      polyarylethersulfone membrane, which correlated with a constant filtrate
      clearance rate, albumin loss was observed. However, no such removal of both HMGB1
      and albumin was observed with the polysulfone membrane and tubing. We conclude
      that continuous hemofiltration using the AN69ST membrane is a promising approach
      for HMGB1-related sepsis.

PMID- 21884475
TI  - Comparison of free light chain removal by four blood purification methods.
AB  - Renal failure is a frequent complication in patients with multiple myeloma.
      Immunoglobulin free light chains (FLCs) form casts in the distal tubules,
      resulting in renal obstruction, and are also directly toxic to proximal renal
      tubules. Removal of FLCs contributes to renal recovery. High cut-off (HCO)
      membrane Theralite2100, protein leaking dialyzer PES210Dalpha, plasma separator
      Evacure1A20 and beta(2) microglobulin adsorption column LixelleS-35 were compared
      in their FLC removal rate. Dialysis using Theralite2100 or Evacure1A20,
      diafiltration using PES210Dalpha and adsorption using LixelleS-35 were performed
      in an in vitro circuit. The highest removal rate was obtained by Theralite2100
      dialysis among the four blood purification methods. Albumin loss was also the
      greatest in Theralite2100 dialysis. The removal content of FLCs per 1 g albumin
      loss was better in PES210Dalpha diafiltration. The removal rate of FLCs by
      Evacure EC1A-20 dialysis was the third highest. Adsorption of FLCs by the beta(2)
      microglobulin adsorption column Lixelle S-35 was confirmed. In conclusion,
      Theralite2100 dialysis was the best in removal of FLCs. PES210Dalpha
      diafiltration can remove FLCs with smaller loss of albumin.

PMID- 21884476
TI  - Complete early virological response was highly achieved by double filtration
      plasmapheresis plus IFN-beta induction therapy for HCV-1b patients with relapse
      or no response after previous IFN therapy.
AB  - The efficacy of double filtration plasmapheresis (DFPP) plus interferon (IFN)
      beta induction therapy was preliminarily investigated in re-treated patients with
      chronic genotype 1b hepatitis C and high viral load (patients with relapse or non
      response to previous IFN therapies). In eight patients with chronic hepatitis C,
      DFPP was performed five times over 2 weeks during IFN-beta therapy, and 3 MU of
      IFN-beta was administered twice a day for 2 weeks. Combination therapies with
      ribavirin and pegylated IFN-alpha2b (PEG-IFN-alpha2b) or pegylated IFN-alpha2a
      (PEG-IFN-alpha2a) were subsequently used. After 4 weeks, hepatitis C virus (HCV)
      RNA tended to be more greatly decreased with DFPP combination therapy than with
      previous IFN therapy (4.5 +/- 2.0 log(10) IU/mL vs. 2.9 +/- 1.2 log(10) IU/mL).
      Rates of both rapid virological response and complete early virological response
      were significantly higher with DFPP and IFN-beta induction therapy than with
      previous IFN therapy. DFPP plus IFN-beta induction therapy produced a great
      reduction of viral load during the early stage of treatment and achieved a high
      early virological response, suggesting that this combination therapy may be
      useful as a new treatment modality for chronic hepatitis C patients in difficult
      to-treat states. This combination may contribute to sustained virological
      response (SVR). The effects of DFPP on SVR and its significance remain to be
      clarified.

PMID- 21884477
TI  - Plasma diafiltration therapy in patients with postoperative liver failure.
AB  - Plasma diafiltration (PDF) is a blood purification therapy in which simple plasma
      exchange (PE) is performed using a selective membrane plasma separator while the
      dialysate flows outside of the hollow fibers. A prospective, multicenter study
      was undertaken to evaluate the changes in biochemical examination of blood and
      the 28-day and 90-day survival rates of patients with postoperative liver failure
      (PLF). Eleven patients with PLF were studied with the therapy performed 98 times.
      The Model for End-Stage Liver Disease (MELD) score was categorized into three
      grades: 20-29, 30-39, and 40 or higher. The survival rate was assessed by the
      severity of MELD score. The 28-day survival rate was 45.5% and that at 90 days
      was 27.3%. The levels of total bilirubin, BUN, and creatinine decreased
      significantly after treatment. On the other hand, the levels of total protein
      increased after treatment and those of albumin did not change significantly. PDF
      may be the useful blood purification therapies for use in cases of PLF in terms
      of medical economics and the removal of water-soluble and albumin-bound toxins.

PMID- 21884479
TI  - Posterior reversible encephalopathy syndrome in systemic lupus erythematosus with
      anti-phospholipid antibodies treated by plasma exchange: a case report.

PMID- 21884478
TI  - A study of appropriate flow rate settings for cell-free and concentrated ascites
      reinfusion therapy and change of cytokine concentrations in ascites.
AB  - We examined appropriate flow rates for high collection rates of Total Protein
      (TP) and Albumin (Alb) and a change of IL-6 concentrations in the cell-free and
      concentrated ascites reinfusion therapy (CART) process. No significant changes
      were observed in IL-6 concentration in the ascites storage test and the
      circulatory stimulation test. However, it was confirmed that the quantity of IL-6
      in the ascites decreased by means of filtration and concentration. In some cases,
      it quickly reached high concentration rates at a higher flow rate (200 mL/min)
      setting, but clogging or pressure increase has occurred in the hollow fiber
      filter. Therefore, it was concluded that a low flow rate (50 mL/min) setting was
      best and provides safer conditions for filtration and concentration in order to
      collect TP and Alb effectively and reuse it as autologous protein, which is the
      primary objective of CART.

PMID- 21884480
TI  - A case of tuberculous lymphadenitis in a dialysis patient with a negative
      QuantiFERON-TB Gold test.

PMID- 21884481
TI  - Could iron deficiency also affect platelet-related hemostasis impairment in
      hemodialysis patients?

PMID- 21884484
TI  - Increasing EPO using the normobaric oxygen paradox: a 'not so simple' task.

PMID- 21884485
TI  - Editorial: Advancing the advance care planning process.

PMID- 21884486
TI  - Editorial: Information and dementia: complexity and the obvious.

PMID- 21884487
TI  - Information provision services in dementia care.
AB  - There are currently 25 million people with dementia worldwide, and this number is
      rising. Dementia has been highlighted as a major priority for health care and
      research because of the enormous economical and health burden associated with it.
      Consultations with people with dementia and carers have highlighted that timely
      well-targeted information services are a key priority for enabling them to 'live
      well with dementia'. Despite this, the evidence base for the optimal design and
      delivery of an information provision service is limited. Findings from randomised
      controlled trials and other studies have indicated that information provision
      does confer some benefit in carer outcomes and in the symptoms and well-being of
      people with dementia. However, there is limited understanding of the optimal
      design of such a service because of the variety of approaches that have been
      evaluated, the wide range of settings and locations and the lack of a clear
      conceptual framework. The existing evidence base supports the importance of an
      optimised information provision service and strongly indicates the need for a
      large-scale RCT to identify the most effective and cost-effective design for
      people with dementia and their carers.

PMID- 21884488
TI  - A model for using the VIPS framework for person-centred care for persons with
      dementia in nursing homes: a qualitative evaluative study.
AB  - BACKGROUND: The 'VIPS' framework sums up the elements in Kitwood's philosophy of
      person-centred care (PCC) for persons with dementia as values, individualised
      approach, the perspective of the person living with dementia and social
      environment. There are six indicators for each element. Aim.  To conduct an
      initial evaluation of a model aimed at facilitating the application of the VIPS
      framework. DESIGN: Qualitative evaluative study. METHODS: A model was trialled in
      a 9-week pilot study in two nursing homes and evaluated in four focus groups
      using qualitative content analysis. RESULTS: Five themes emerged: (1) Legitimacy
      of the model was secured when central roles were held by nurses representing the
      majority of the staff; (2) The model facilitated the staff's use of their
      knowledge of PCC; (3) Support to the persons holding the internal facilitating
      roles in the model was needed; (4) The authority of the leading registered nurse
      in the ward was crucial to support the legitimacy of the model and (5) Form of
      organisation seemed to be of importance in how the model was experienced.
      CONCLUSION: The model worked best in wards organised with a leading registered
      nurse who could support an auxiliary nurse holding the facilitating function.

PMID- 21884489
TI  - Information in dementia care: sense making and a public health direction for the
      UK?
AB  - Providing information is a core focus of policy and practice in dementia care.
      Information is a vehicle through which people can be enabled or disabled, so it
      is essential that we ensure that information is available in a way that is
      accessible and relevant for people with dementia and that it enables personal
      aspiration and collective identity to be advanced in a way that is to the benefit
      of those living with dementia. People with dementia need information to support
      autonomy in making decisions and in acting on those decisions. Information must
      be provided in a way that is appropriate to the individual and to achieve that
      requires knowledge of the needs of that individual. However, maintaining autonomy
      includes, but involves much more than, the provision of information - others need
      to listen and hear their views and be prepared to act on them. As professionals,
      we must be aware that the (dementia) information we provide may disrupt the
      biographical narrative that people with dementia value. Thus, a person-centred
      approach encourages the sharing of knowledge and information. The (mis)use of
      information also impacts on the way that society disables, discriminates and
      applies barriers against people with disability.

PMID- 21884490
TI  - Progressive resistance strength training for improving physical function in older
      adults.

PMID- 21884491
TI  - Forty-five isn't old!

PMID- 21884492
TI  - Perinatal depression.

PMID- 21884494
TI  - Caffeine and breast pain: revisiting the connection.

PMID- 21884495
TI  - Understanding the breast crawl: implications for nursing practice.

PMID- 21884496
TI  - Elective cesarean delivery: trends, evidence and implications for women, newborns
      and nurses.

PMID- 21884497
TI  - Approaching menopause (but not there yet!): caring for women in midlife.

PMID- 21884498
TI  - Pertussis: an ounce of prevention.

PMID- 21884499
TI  - Food allergies in the hospital setting: prevention, treatment and patient
      education.

PMID- 21884500
TI  - Have the best of both worlds: professional growth opportunities for bedside
      nurses.

PMID- 21884501
TI  - The partnership for patients: improving care and reducing complications.

PMID- 21884502
TI  - Coalition for quality maternal care: advocating for mothers and newborns.

PMID- 21884503
TI  - Health information technology for the perinatal setting.

PMID- 21884504
TI  - Earning my wings.

PMID- 21884505
TI  - An assessment of three noncommercial DNA extraction methods from dried blood
      spots for beta-thalassaemia mutation identification.
AB  - INTRODUCTION: Dried blood spots (DBS) are currently the recommended sample
      collection method for newborn screening programmes in America. Early diagnosis of
      beta-thalassaemia screening is essential as it provides an added advantage
      especially in sickle cell disease. Beta-thalassaemia frequency is high in many
      poor countries, and the cost of using commercial DNA extraction kits can be
      prohibitive. Our study assessed three methods that use minimal reagents and
      materials to extract DNA from DBS for beta-thalassaemia identification. METHODS:
      The methods assessed in this study were Tris-EDTA (TE) buffer-based method by
      Bereczky et al. (American Journal of Tropical Medicine and Hygiene 72, 2005,
      249), NaCL/NaOH/Sodium dodecyl sulphate (SDS) method by Huang et al. (Human
      Genetics 84, 1990, 129) and NaOH method by Zhou et al. (Analytical Biochemistry
      354, 2006, 159). Extracted DNA was amplified for three common beta-thalassaemia
      mutations in Malaysia. RESULTS: Amplicons derived from TE buffer-based method
      were very faint and almost nonexistent while the NaCl/NaOH/SDS method did not
      produce any visible amplicons. The extraction using NaOH method produced visible
      bands that were comparable to the standard method using extraction kit.
      CONCLUSION: The NaOH method is a simple method that uses minimal equipment and
      reagents that make it labour- and cost-effective. This method could be adopted by
      poorer countries to extract DNA for beta-thalassaemia mutation characterization.

PMID- 21884506
TI  - Scientific publishing in the electronic age.

PMID- 21884507
TI  - Patients as a scientific resource: comments on receiving the Ahrens award.

PMID- 21884508
TI  - The Clinical and Translational Science Awards (CTSAs) are transforming the way
      academic medical institutions approach translational research: the University of
      Michigan Experience.

PMID- 21884509
TI  - Cytosolic phospholipase A(2)alpha protects against ischemia/reperfusion injury in
      the heart.
AB  - Studies with sPLA(2) Group X, and cPLA(2) alpha gene-targeted mice suggest that
      absence of sPLA(2) Group X results in protection from ischemia/reperfusion (I/R)
      injury in the heart, and absence of cPLA(2) alpha Group IV is protective in the
      brain. Although latter studies might suggest a similar deleterious role for
      cPLA(2) alpha in I/R injury in the heart, the pathophysiology of stroke is
      intricately related to excitotoxicity and cannot necessarily be extrapolated to
      the heart. We report here that unlike findings in the brain, cPLA(2) alpha((-/-))
      mice have exaggerated injury following I/R in vivo. In contrast, there is no
      difference in injury induced by simulated ischemia in cardiomyocytes isolated
      from cPLA(2) alpha((-/-)) versus cPLA(2) alpha((+/+)) mice. This suggests that
      cPLA(2) alpha does not have an important cardiomyocyte autonomous effect on
      ischemic injury. Prostaglandin E(2) (PGE(2) ) levels are significantly reduced in
      the hearts of the cPLA(2) alpha((-/-)) mice, and the enhanced injury is
      ameliorated by treatment with the PGE analog, misoprostol. We demonstrate that
      cPLA(2) alpha is cardioprotective in vivo, and this is likely via cPLA(2) alpha
      mediated production of cardioprotective eicosanoids. These studies are the first
      to identify a protective role for cPLA(2) in I/R injury in any organ and raise
      concerns over long-term inhibition of cPLA(2).

PMID- 21884511
TI  - High levels of zinc-protoporphyrin identify iron metabolic abnormalities in
      pulmonary arterial hypertension.
AB  - Iron homeostasis influences the development of pulmonary arterial hypertension
      (PAH) associated with hypoxia or hematologic disorders. To investigate whether
      severity of idiopathic PAH (IPAH) is impacted by alterations in iron metabolism,
      we assessed iron metabolic markers, including levels of zinc-protoporphyrin (Zn
      pp), transferrin receptor, and red blood cell numbers and morphology in IPAH,
      associated PAH and sleep apnea-induced pulmonary hypertension patients in
      comparison to healthy controls and asthmatics. Despite similarly normal measures
      of iron metabolism, Zn-pp levels in IPAH and sleep apnea patients were elevated
      approximately twofold, indicating deficient iron incorporation to form heme and
      levels were closely related to measures of disease severity. Consistent with high
      Zn-pp, PAH patients had increased red cell distribution width (RDW). In an
      expanded cohort including patients with IPAH and familial disease, the RDW was
      validated and related to clinical parameters of severity; including pulmonary
      artery pressures and 6-minute walk distances. These results reveal an increased
      prevalence of subclinical functional iron deficiency in primary forms of PAH that
      is quantitatively related to disease severity. This suggests that altered iron
      homeostasis influences disease progression and demonstrates the importance of
      closely monitoring iron status in PAH patients.

PMID- 21884512
TI  - Partnership-driven Resources to Improve and Enhance Research (PRIMER): a survey
      of community-engaged researchers and creation of an online toolkit.
AB  - OBJECTIVE: This project aimed to develop an open-access website providing
      adaptable resources to facilitate best practices for multisite research from
      initiation to closeout. methods: A web-based assessment was sent to the
      leadership of the Clinical and Translational Science Award (CTSA) Community
      Engagement Key Functions Committee (n= 38) and the CTSA-affiliated Primary Care
      Practice-based Research Networks (PBRN, n= 55). Respondents rated the benefits
      and barriers of multisite research, the utility of available resources, and
      indicated their level of interest in unavailable resources. Then, existing
      research resources were evaluated for relevance to multisite research,
      adaptability to other projects, and source credibility. RESULTS: Fifty-five (59%)
      of invited participants completed the survey. Top perceived benefits of multisite
      research were the ability to conduct community-relevant research through academic
      community partnerships (34%) and accelerating translation of research into
      practice (31%). Top perceived barriers were lack of research infrastructure to
      support PBRNs and community partners (31%) and inadequate funding to support
      multisite collaborations (26%). Over 200 resources were evaluated, of which 120
      unique resources were included in the website. CONCLUSION: The PRIMER Research
      Toolkit (http://www.researchtoolkit.org) provides an array of peer-reviewed
      resources to facilitate translational research for the conduct of multisite
      studies within PBRNs and community-based organizations.

PMID- 21884510
TI  - Fructose-fed rhesus monkeys: a nonhuman primate model of insulin resistance,
      metabolic syndrome, and type 2 diabetes.
AB  - The incidence of insulin resistance has increased dramatically over the past
      several years, and we and others have proposed that this increase may at least in
      part be attributable to increased dietary fructose consumption. However, a major
      limitation to the study of diet-induced insulin resistance is the lack of
      relevant animal models. Numerous studies, mostly in rodents, have demonstrated
      that diets high in fructose induce insulin resistance; however, important
      metabolic differences exist between rodents and primates. Thus, the results of
      metabolic studies performed in primates are substantively more translatable to
      human physiology, underscoring the importance of establishing nonhuman primate
      models of common metabolic conditions. In this report, we demonstrate that a high
      fructose diet in rhesus monkeys produces insulin resistance and many features of
      the metabolic syndrome, including central obesity, dyslipidemia, and inflammation
      within a short period of time; moreover, a subset of monkeys developed type 2
      diabetes. Given the rapidity with which the metabolic changes occur, and the
      ability to control for many factors that cannot be controlled for in humans,
      fructose feeding in rhesus monkeys represents a practical and efficient model
      system in which to investigate the pathogenesis, prevention, and treatment of
      diet-induced insulin resistance and its related comorbidities.

PMID- 21884513
TI  - Streamlining research by using existing tools.
AB  - Over the past two decades, the health research enterprise has matured rapidly,
      and many recognize an urgent need to translate pertinent research results into
      practice, to help improve the quality, accessibility, and affordability of US
      healthcare. Streamlining research operations would speed translation,
      particularly for multisite collaborations. However, the culture of research
      discourages reusing or adapting existing resources or study materials. Too often,
      researchers start studies and multisite collaborations from scratch-reinventing
      the wheel. Our team developed a compendium of resources to address inefficiencies
      and researchers' unmet needs and compiled them in a research toolkit website
      (http://www.ResearchToolkit.org). Through our work, we identified philosophical
      and operational issues related to disseminating the tool kit to the research
      community. We explore these issues here, with implications for the nation's
      investment in biomedical research.

PMID- 21884514
TI  - Prostaglandin E2 and IL-23 plus IL-1beta differentially regulate the Th1/Th17
      immune response of human CD161(+) CD4(+) memory T cells.
AB  - Prostaglandin E2 (PGE2), interleukin (IL)-23, and IL-1beta (beta) propagate
      inflammatory bowel disease (IBD) by enhancing the development and function of IL
      17 producing CD4(+) T helper (Th17) cells. CD4(+) T cells that express the C-type
      lectin-like receptor CD161 have been proposed to be the physiologic pool of
      circulating Th17 cells implicated in IBD. We sought to understand how PGE2, alone
      and in combination with IL-23 and IL-1beta, modulate human peripheral CD161(+)
      CD4(+) memory T cells. We found that CD161(+) cells comprise a significant
      proportion of human peripheral CD4(+) memory T cells. PGE2 and IL-23 plus IL
      1beta synergistically induced early IL-17A secretion from CD161(+) CD4(+) memory
      T cells and the selective enrichment of IL-17A(+) CD161(+) CD4(+) memory T cells
      in culture. Conversely, IL-23 plus IL-1beta partially opposed the PGE2-mediated
      repression of early interferon gamma (IFN-gamma) secretion from CD161(+) cells,
      as well as the PGE2-mediated depletion of IFN-gamma(+) CD161(+) cells. Our
      results suggest that PGE2 and IL-23 plus IL-1beta induce the Th17 immune response
      preferentially in CD161(+) CD4(+) memory T cells, while divergently regulating
      their ability to express IFN-gamma. We hypothesize that Th17-mediated chronic
      inflammation in IBD depends on the net response of CD161(+) CD4(+) memory T cells
      to both PGE2 and IL-23 plus IL-1beta.

PMID- 21884515
TI  - To join or not to join: an investigation of individual facilitators and
      inhibitors of medical faculty participation in interdisciplinary research teams.
AB  - Interdisciplinary research (IDR) teams are an important mechanism for
      facilitating medical breakthroughs. This study investigates the role of
      individual-level predictors of the choice to join a new IDR team at a major
      medical institution. We collected survey data from a sample of 233 faculty
      members who were given the opportunity to participate in IDR teams that had
      recently formed around a wide range of medical topic areas. Our results suggest
      that even under supportive organizational conditions, some medical experts were
      more likely to participate than others. Specifically, basic and translational
      researchers, associate professors, and faculty with distinctive topic area
      expertise and with more experience collaborating across departmental boundaries
      participated at a greater rate than their peers. Our findings have implications
      for research, practice, and policy focused on overcoming the challenges of
      drawing together diverse medical experts into IDR teams with the potential to
      advance knowledge to prevent, cure, and treat complex medical conditions.

PMID- 21884516
TI  - Translating gene transfer: a stalled effort.
AB  - The journey of gene transfer from laboratory to clinic has been slow and fraught
      with many challenges and barriers. Despite the development of the initial
      technology in the early 1970s, a standard clinical treatment involving "gene
      therapy" remains to be seen. Furthermore, much was written about the technology
      in the early 1990s, but since then, not much has been written about the journey
      of gene transfer. The translational path of gene transfer thus far, both pitfalls
      and successes, can serve as a study not only in navigating ethical and safety
      concerns, but also in the importance of scientist-public interactions. Here, we
      examine the translational progress of gene transfer and what can be gleaned from
      its history.

PMID- 21884517
TI  - IL28B genotype does not correlate with HIV control in African Americans.
AB  - BACKGROUND: HIV-1 natural viral suppressors (NVS) are individuals that control
      HIV replication without antiretrovirals (also know as HIV elite controllers). We
      have recently shown that these individuals have an elevated rate of hepatitis C
      virus (HCV) clearance. Given the association of IL28B genotype, specifically the
      rs12979860 single nucleotide polymorphism (SNP) based CC genotype, with HCV
      clearance, we studied its association with HIV control in 172 African American
      HIV subjects and 173 race-matched controls. FINDINGS: The frequency of the CC
      genotype was 12.5% in the NVS, 14.7% in the LVL ("low viral load" cohort with 400
      20,000 HIV-1 RNA copies/mL), 17.8% in the MHVL ("medium/high viral load" cohort
      with >20,000 HIV-1 RNA copies/mL), and 11.6% in an HIV-negative cohort. There was
      no statistical significance in the CC genotype distribution between these cohorts
      (p= 0.48 between the NVS and non-NVS HIV positive controls, p= 0.85 between NVS
      and HIV-negatives). We also did not observe any association between CC genotype
      distribution and HIV RNA viral load, as a continuous measure. CONCLUSIONS: The
      IL28B CC genotype does not account for the noted HIV control in our specific NVS
      cohort. Further studies will be needed to determine if a common genetic factor
      can primarily account for any joint clearance of HCV and control of HIV.

PMID- 21884518
TI  - Beyond the medical model: interdisciplinary programs of community-engaged health
      research.
AB  - This report describes four diverse programs of community-engaged research, all of
      which demonstrated positive health outcomes. Three of the programs were focused
      on communities of people with diabetes, and one program targeted at-risk young
      families raising infants and young children. Brief descriptions of each research
      study and outcomes are presented as well as a discussion of the processes and
      lessons that were learned from each model of successful interdisciplinary
      community-university health research partnerships.

PMID- 21884519
TI  - Homologous recombination in human embryonic stem cells: a tool for advancing cell
      therapy and understanding and treating human disease.
AB  - Human embryonic stem cells (hESCs) hold great promise for ushering in an era of
      novel cell therapies to treat a wide range of rare and common diseases, yet they
      also provide an unprecedented opportunity for basic research to yield clinical
      benefit. HESCs can be used to better understand human development, to model human
      diseases, to understand the contribution of specific mutations to the
      pathogenesis of disease, and to develop human cell-based screening systems to
      identify novel therapeutic agents and evaluate potential toxicity of therapeutic
      agents under development. Such basic research will benefit greatly from efficient
      methods to perform targeted gene modification, an area of hESC investigation that
      is currently in its infancy. Moreover, the reality of hESC-based cellular
      therapies will require improved methods for generating the specific cells of
      interest, and reporter cell lines generated through targeted gene modifications
      are expected to play an important role in developing optimal cell-specific
      differentiation protocols. Herein, we review the current status of homologous
      recombination in hESCs, a gene targeting technique that is sure to continue to
      improve, and to play an important role in realizing the maximal human benefit
      from hESCs.

PMID- 21884521
TI  - Acta Ophthalmologica and EVER - 5 years later.

PMID- 21884523
TI  - Autistic symptoms in childhood arrestees: longitudinal association with
      delinquent behavior.
AB  - BACKGROUND: To compare childhood arrestees with matched comparison groups on
      levels of autistic symptoms and to assess the unique predictive value of autistic
      symptoms for future delinquent behavior in childhood arrestees. METHODS:
      Childhood first-time arrestees (n = 308, baseline age 10.7 +/- 1.5 years) were
      followed up for 2 years. Autistic symptoms, externalizing disorders and
      delinquent behavior were assessed yearly. Childhood arrestees were compared on
      autistic symptoms with matched (age, gender) general population and clinical
      autism spectrum disorder samples. The predictive value of autistic symptoms for
      delinquent behavior was analyzed using generalized estimating equations. RESULTS:
      At each assessment, levels of autistic symptoms in childhood arrestees were in
      between levels found in the general population and autism spectrum disorder
      samples. Autistic symptoms were positively associated with delinquent behavior in
      childhood arrestees, even after adjustment for externalizing disorders: IRR
      (incidence rate ratio) 1.23; 95% CI 1.11-1.36 and IRR 1.29; 95% CI 1.15-1.45 for
      core autistic symptoms and total symptom score, respectively. CONCLUSIONS:
      Autistic symptoms are more prevalent in childhood arrestees compared to the
      general population and are uniquely associated with future delinquent behavior.
      Attention should, therefore, be given to the possible presence of autism related
      symptomatology in these children. Implications for diagnostic assessment and
      intervention need further investigation.

PMID- 21884522
TI  - Gene by environment interactions influencing reading disability and the
      inattentive symptom dimension of attention deficit/hyperactivity disorder.
AB  - BACKGROUND: Reading disability (RD) and attention deficit/hyperactivity disorder
      (ADHD) are comorbid and genetically correlated, especially the inattentive
      dimension of ADHD (ADHD-I). However, previous research indicates that RD and ADHD
      enter into opposite gene by environment (G * E) interactions. METHODS: This study
      used behavioral genetic methods to replicate these opposite G * E interactions in
      a sample of same-sex monozygotic and dizygotic twin pairs from the Colorado
      Learning Disabilities Research Center (CLDRC; DeFries et al., 1997) and to test a
      genetic hypothesis for why these opposite interactions occur. RESULTS: We
      replicated opposite G * E interactions for RD (bioecological) and ADHD-I
      (diathesis-stress) with parental education in the same sample of participants.
      The genetic hypothesis for this opposite pattern of interactions is that only
      genes specific to each disorder enter into these opposite interactions, not the
      shared genes underlying their comorbidity. To test this hypothesis, we used
      single models with an exploratory three-way interaction, in which the G * E
      interactions for each disorder were moderated by comorbidity. Neither three-way
      interaction was significant. The heritability of RD did not vary as a function of
      parental education and ADHD-I. Similarly, the heritability of ADHD-I did not vary
      as a function of parental education and RD. CONCLUSIONS: We documented opposite G
      * E interactions in RD and ADHD-I in the same overall twin sample, but the
      explanation for this apparent paradox remains unclear. Examining specific genes
      and more specific environmental factors may help resolve the paradox.

PMID- 21884524
TI  - alpha7 Nicotinic receptor activation reduces beta-amyloid-induced apoptosis by
      inhibiting caspase-independent death through phosphatidylinositol 3-kinase
      signaling.
AB  - The neurotoxicity of amyloid-beta (Abeta) involves caspase-dependent and 
      independent programmed cell death. The latter is mediated by the nuclear
      translocation of the mitochondrial flavoprotein apoptosis inducing factor (AIF).
      Nicotine has been shown to decrease Abeta neurotoxicity via inhibition of caspase
      dependent apoptosis, but it is unknown if its neuroprotection is mediated through
      caspase-independent pathways. In the present study, pre-treatment with nicotine
      in rat cortical neuronal culture markedly reduced Abeta(1-42) induced neuronal
      death. This effect was accompanied by a significant reduction of mitochondrial
      AIF release and its subsequent nuclear translocation as well as significant
      inhibition of cytochrome c release and caspase 3 activation. Pre-treatment with
      selective alpha7nicotinic acetylcholine receptor(nAChR) antagonist
      (methyllycaconitine), but not the alpha4 nAChR antagonist (dihydro-beta
      erythroidine), could prevent the neuroprotective effect of nicotine on AIF
      release/translocation, suggesting that nicotine inhibits the caspase-independent
      death pathway in a alpha7 nAChR-dependent fashion. Furthermore, the
      neuroprotective action of nicotine on AIF release/translocation was suppressed by
      LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor. Pre-treatment with
      nicotine significantly restored Akt phosphorylation, an effector of PI3K, in
      Abeta(1-42) -treated neurons. These findings indicate that the alpha7 nAChR
      activation and PI3K/Akt transduction signaling contribute to the neuroprotective
      effects of nicotine against Abeta-induced cell death by modulating caspase
      independent death pathways.

PMID- 21884526
TI  - Danger at your door: pathogen signals and programmed cell death in plants.

PMID- 21884525
TI  - Ethanol causes the redistribution of L1 cell adhesion molecule in lipid rafts.
AB  - Fetal alcohol spectrum disorder is estimated to affect 1% of live births. The
      similarities between children with fetal alcohol syndrome and those with
      mutations in the gene encoding L1 cell adhesion molecule (L1) implicates L1 as a
      target of ethanol developmental neurotoxicity. Ethanol specifically inhibits the
      neurite outgrowth promoting function of L1 at pharmacologic concentrations.
      Emerging evidence shows that localized disruption of the lipid rafts reduces L1
      mediated neurite outgrowth. We hypothesize that ethanol impairment of the
      association of L1 with lipid rafts is a mechanism underlying ethanol's inhibition
      of L1-mediated neurite outgrowth. In this study, we examine the effects of
      ethanol on the association of L1 and lipid rafts. We show that, in vitro, L1 but
      not N-cadherin shifts into lipid rafts following treatment with 25 mM ethanol.
      The ethanol concentrations causing this effect are similar to those inhibiting L1
      mediated neurite outgrowth. Increasing chain length of the alcohol demonstrates
      the same cutoff as that previously shown for inhibition of L1-L1 binding. In
      addition, in cerebellar granule neurons in which lipid rafts are disrupted with
      methyl-beta-cyclodextrin, the rate of L1-mediated neurite outgrowth on L1-Fc is
      reduced to background rate and that this background rate is not ethanol
      sensitive. These data indicate that ethanol may inhibit L1-mediated neurite
      outgrowth by retarding L1 trafficking through a lipid raft compartment.

PMID- 21884527
TI  - Timescales and timetrees.

PMID- 21884528
TI  - Placental immunology and maternal alloimmune responses.
AB  - During pregnancy, women are tolerant of their semi-allogeneic fetus whilst not
      being immunosuppressed and indeed readily form alloantibodies. This
      'Immunological Paradox of Pregnancy' may be explained by an understanding of
      placental anatomy and immunology. Trophoblast cells form the interface between
      the fetus and maternal tissues and blood and escape allorecognition because they
      lack classical human leucocyte antigen (HLA) class I and II molecules. Local
      immunoregulation, or tolerance, in the decidua is mediated partly by HLA-G(+) 
      extravillous trophoblasts (EVT) that invade the tissue and prevent killing by
      maternal natural killer cells, cytotoxic T cells and macrophages. Placental
      hormones orchestrate the composition and regulatory function of maternal immune
      cells. In contrast, syncytiotrophoblast cells at the surface of chorionic villi,
      in contact with maternal blood, maintain a state of mild maternal systemic
      immunity via activation of innate immunity and skewing towards humoral immunity.
      This enables maintenance of a healthy immune system in pregnant women and robust
      protective antibody responses to pathogens whilst enabling survival of the fetus.
      However, this has the unfortunate consequence that pregnant women readily form
      alloantibodies to incompatible alloantigens on fetal red cells, platelets and
      leucocytes if fetomaternal haemorrhage (FMH) occurs. The antibodies are initially
      low affinity but after re-immunization with further FMH become functionally
      effective, high-titre IgG.

PMID- 21884530
TI  - Distinct eosinophil cytokine expression patterns in skin diseases - the possible
      existence of functionally different eosinophil subpopulations.
AB  - BACKGROUND: The function of eosinophils has been attributed to host defense,
      immunomodulation, and fibrosis. Although eosinophils are found among infiltrating
      cells in a broad spectrum of skin diseases, their pathogenic role remains
      uncertain. This study aimed to analyze the cytokine expression by eosinophils in
      different skin diseases. METHODS: Skin specimens from different skin diseases
      [allergic/reactive, infectious, autoimmune, and tumors/lymphomas (LY)] were
      stained by antibodies directed to eosinophil cationic protein, cytokines [tumor
      necrosis factor (TNF)-alpha, interleukin (IL)-5, IL-6, IL-10, IL-11, IL-13, IL
      17, IL-25, IL-33, interferon-gamma, transforming growth factor (TGF)-beta, and
      thymic stromal lymphopoietin], eotaxins (CCL11, CCL24, and CCL26),
      metalloproteinase (MMP)-9 as well as extracellular matrix proteins (tenascin-C
      and procollagen-3) and then analyzed by laser scanning microscopy. RESULTS: The
      number of eosinophils varied considerably in and between disease groups and did
      not correlate with the numbers of accompanying inflammatory cells. The expression
      of IL-5, IL-6, IL-11, TGF-beta, CCL24, and MMP-9 by eosinophils significantly
      differed between disease groups. Eosinophils in tumors/LY predominantly expressed
      IL-6, TGF-beta, and CCL24, but not IL-11. On the other hand, in autoimmune
      diseases, eosinophils largely contributed to MMP-9 production. IL-5-generating
      eosinophils were particularly obvious in allergic and infectious diseases.
      CONCLUSION: In skin diseases, eosinophil expresses a broad spectrum of cytokines.
      The different cytokine expression patterns suggest distinct functional roles of
      eosinophils in these diseases that might be related to host defense,
      immunomodulation, fibrosis, and/or tumor development.

PMID- 21884529
TI  - Lack of efficacy of long-term, low-dose azithromycin in chronic rhinosinusitis: a
      randomized controlled trial.
AB  - BACKGROUND: In persistent chronic rhinosinusitis (CRS), conventional treatment is
      often insufficient. Long-term, low-dose administration of macrolides has been
      suggested as a treatment option. The MACS (Macrolides in chronic rhinosinusitis)
      study is a randomized placebo-controlled trial evaluating the efficacy of
      azithromycin (AZM) in CRS. METHODS: We describe a group of patients with
      recalcitrant CRS with and without nasal polyps unresponsive to optimal medical
      and (in 92% also) surgical treatment. Patients were treated with AZM or placebo.
      AZM was given for 3 days at 500 mg during the first week, followed by 500 mg per
      week for the next 11 weeks. Patients were monitored until 3 months post-therapy.
      The assessments included Sino-Nasal Outcome Test-22 (SNOT-22), a Patient Response
      Rating Scale, Visual Analogue Scale (VAS), Short Form-36 (SF-36), rigid nasal
      endoscopy, peak nasal inspiratory flow (PNIF), Sniffin' Sticks smell tests and
      endoscopically guided middle meatus cultures. RESULTS: Sixty patients with a
      median age of 49 years were included. Fifty per cent had asthma and 58% had
      undergone revision sinus surgery. In the SNOT-22, Patient Response Rating Scale,
      VAS scores and SF-36, no significant difference between the AZM and the placebo
      groups was demonstrated. Nasal endoscopic findings, PNIF results, smell tests and
      microbiology showed no relevant significant differences between the groups
      either. CONCLUSION: At the investigated dose of AZM over 3 months, no significant
      benefit was found over placebo. Possible reasons could be disease severity in the
      investigated group, under-dosage of AZM and under-powering of the study.
      Therefore, more research is urgently required.

PMID- 21884531
TI  - Spontaneous resolution of diphtheria-tetanus vaccine hypersensitivity in a
      pediatric population.

PMID- 21884532
TI  - Thunderstorm-related asthma epidemic owing to Olea Europaea pollen sensitization.

PMID- 21884533
TI  - C1 esterase inhibitor concentrate in 1085 Hereditary Angioedema attacks--final
      results of the I.M.P.A.C.T.2 study.
AB  - BACKGROUND: The placebo-controlled study International Multicentre Prospective
      Angioedema C1-INH Trial 1 (I.M.P.A.C.T.1) demonstrated that 20 U/kg C1 esterase
      inhibitor (C1-INH) concentrate (Berinert(r); CSL Behring, Marburg, Germany) is
      effective in treating acute abdominal and facial Hereditary Angioedema (HAE)
      attacks. METHODS: I.M.P.A.C.T.2 was an open-label extension study of
      I.M.P.A.C.T.1 to evaluate the safety and efficacy of long-term treatment with 20
      U/kg C1-INH for successive HAE attacks at any body location. Efficacy outcomes
      included patient-reported time to onset of symptom relief (primary) and time to
      complete resolution of all symptoms (secondary), analysed on a per-patient and
      per-attack basis. Safety assessments included adverse events, vital signs, viral
      safety and anti-C1-INH antibodies. RESULTS: During a median study duration of 24
      months, 1085 attacks were treated in 57 patients (10-53 years of age). In the per
      patient analysis, the median time to onset of symptom relief was 0.46 h and was
      similar for all types of attacks (0.39-0.48 h); the median time to complete
      resolution of symptoms was 15.5 h (shortest for laryngeal attacks: 5.8 h; 12.8
      26.6 h for abdominal, peripheral and facial attacks). Demographic factors, type
      of HAE, intensity of attacks, time to treatment, use of androgens and presence of
      anti-C1-INH antibodies had no clinically relevant effect on the efficacy
      outcomes. There were no treatment-related safety concerns. No inhibitory anti-C1
      INH antibodies were detected in any patient. CONCLUSIONS: A single dose of 20
      U/kg C1-INH concentrate is safe and provides reliable efficacy in the long-term
      treatment of successive HAE attacks at any body location.

PMID- 21884534
TI  - Hematopoietic progenitor cells are innate Th2 cytokine-producing cells.
AB  - Typically, hematopoietic stem/progenitor cells (HSPCs) reside within the bone
      marrow (BM) where they give rise to all hematopoietic populations. However, HSPCs
      also constantly egress from the BM into the blood and circulate through the
      peripheral tissues where upon encounter with inflammatory stimuli and epithelial
      cell-derived cytokines they rapidly release very high levels of Th2
      cytokines/chemokines and differentiate into Th2 effector cells. The novel concept
      of the dual function of HSPCs as hematopoietic precursors and potent Th2 cytokine
      producers has important clinical implications in various inflammatory conditions,
      including allergic diseases.

PMID- 21884536
TI  - The benefits of a critical stance: a reflection on past papers on the theories of
      reasoned action and planned behaviour.
AB  - In this paper, I reflect on past papers published in the British Journal of
      Social Psychology (BJSP) that have played a role in the development of the theory
      of reasoned action (TRA) and the theory of planned behaviour (TPB). I focus on
      seven papers that fall into five categories: (1) those that critique the TRA/TPB
      for taking insufficient account of social factors; (2) those that critique the
      models on the grounds that many social behaviours are 'habitual'; (3) those that
      critically examine the construct of perceived behavioural control; (4) those that
      argue for the importance of affective factors, which appear to be overlooked in
      the TRA/TPB; and (5) those that argue for the importance of studying the role of
      moderating factors and interaction effects in the TRA/TPB. I conclude that BJSP's
      traditional focus on criticism and theory development is one that benefits the
      journal and the field.

PMID- 21884537
TI  - Fifty-odd years of inter-group contact: from hypothesis to integrated theory.
AB  - We review 50-odd years of research on Allport's (1954)'contact hypothesis', to
      assess progress, problems, and prospects. We chart the progress that has been
      made in understanding two distinct forms of contact: direct and indirect. We
      highlight the progress made in understanding the effects of each type of contact,
      as well as both moderating and mediating factors, and emphasize the multiple
      impacts of direct contact, especially. We then consider some of the main
      critiques of inter-group contact, focusing on empirical issues and whether
      contact impedes social change, and provide a research agenda for the coming
      years. We conclude that this body of work no longer merits the modest title of
      'hypothesis', but fully deserves acknowledgement as an integrated and influential
      theory.

PMID- 21884538
TI  - BJSP and the changing face of the group in social psychology.
AB  - I reflect on the contribution that BJSP has made to the conceptualization of the
      group within social psychology by highlighting two cases studies from the social
      identity tradition published in 1990. These illustrate BJSP's distinctive
      strength and openness to theoretical innovation over the last decades.

PMID- 21884539
TI  - Promoting a culture of innovation: BJSP and the emergence of new paradigms in
      social psychology.
AB  - In this paper, I start by describing the role played by British Journal of Social
      Psychology (BJSP) in nurturing two important new paradigms in social psychology -
      the social identity approach and discourse psychology. I then consider the forces
      in contemporary academia, in general, and psychology, in particular, that
      militate against innovation. I conclude by suggesting some ways in which
      individual social psychologists and our journals, particularly BJSP, can
      contribute to the development of an innovative and intellectually dynamic
      discipline.

PMID- 21884540
TI  - The winds of change: some challenges in reconfiguring social psychology for the
      future.
AB  - In this short article, I celebrate the plurality and eclecticism of the British
      Journal of Social Psychology. I argue that this approach offers the best hope for
      an uncertain future. The powerful narrative on which social psychology was once
      based is fragmenting in part due to Research Assessment Exercise (RAE/REF)
      pressures. Social psychological topics and research are migrating outside
      institutional Psychology, and the BJSP needs to follow. Examples of recent social
      research on affect and emotion are used to illustrate the new spreading and reach
      of social psychological topics and issues.

PMID- 21884541
TI  - How social is the social psychology of emotion?
AB  - Two classic studies published 50 years ago showed how other people provide
      information that shapes the activation and interpretation of emotions. The
      present paper traces development of the social psychology of emotions from this
      starting point. Subsequent research into group-based and social appraisal has
      advanced understanding of the impact of social information on emotions and
      suggested new ways of investigating associated phenomena. Although potential
      integrations of interpersonal and group-oriented approaches offer promise for the
      future, the continuing focus on emotions as cognitively mediated effects of
      social factors should broaden to encompass dynamic relational processes.

PMID- 21884542
TI  - Facing social identity change: interactive effects of current and projected
      collective identification on expectations regarding future self-esteem and
      psychological well-being.
AB  - We hypothesized that prospective changes in social identity that involve
      transitioning out of a currently valued group would be associated with negative
      expectations regarding future states, but that this effect would be mitigated
      among individuals who expect to belong to a future in-group of similar
      importance. Consistent with predictions, strongly identified young adults in two
      studies projected significantly lower self-esteem/psychological well-being in old
      age than weakly identified young adults. Critically, however, this effect was
      fully attenuated if they expected to identify with their future aged in-group
      when they were old. Study 2 showed that the capacity for projected identification
      to buffer projected well-being among strongly identified young adults was
      contingent on their membership in the future in-group being highly salient.
      Analyses of participants' written descriptions of old age (Study 1) and a valence
      manipulation (Study 2) indicated that these effects were not attributable to the
      anticipated valence of future selves/states, but rather to the value placed on
      current and future group memberships.

PMID- 21884543
TI  - Cues to deception in context: response latency/gaps in denials and blame
      shifting.
AB  - Over 40 years of work on lying in psychology and communication has investigated
      numerous 'cues to deception'- the subtle signals people show when they are lying.
      One of these cues to deception is 'response latency' or the gap that occurs
      between questions and the lying response. The current investigation uses the
      methodology of conversation analysis to re-consider the question of response
      latency in the context of lying. Drawing on data from two naturalistic sources,
      the television shows COPS and the Jeremy Kyle Show, this investigation analyses
      response latencies in order to show the regular organization of gaps between
      turns in both lies and non-lies. The current investigation demonstrates that in
      blame shifting turns which are lies, any gaps between turns result from a display
      of upcoming 'trouble', rather than being related to lying per se. The
      investigation highlights the need to analyse lies in the contexts in which they
      are told, taking prior and subsequent talk into account.

PMID- 21884544
TI  - Dilemmas of citizenship: young people's conceptions of un/employment rights and
      responsibilities.
AB  - This paper draws on the concept of ideological dilemmas in order to explore how a
      sample of young people constructed potentially contrary themes of liberal
      citizenship in discussions of un/employment. The study took place in the context
      of recent policy developments in the UK which have sought to place a renewed
      emphasis upon notions of responsible citizenship in relation to both welfare and
      education policy. A total of 58 participants were interviewed in 24 semi
      structured group interviews. In response to direct questions on un/employment,
      participants could resolve dilemmas concerning welfare rights and the
      responsibility to contribute to society by emphasizing a criterion of
      effortfulness, thereby adopting a primarily individualistic explanation of
      unemployment. In other contexts however, this could be replaced by an emphasis on
      social explanations of unemployment. In particular, participants could treat
      immigration as a cause of unemployment. These findings are interpreted in terms
      of people's capacity to construct rhetorical strategies based upon different
      ideological themes in particular contexts. They are discussed in relation to
      previous research on social policy discourse and recent debates regarding the
      appropriateness of seeking to identify ideological themes in discourse.

PMID- 21884545
TI  - Blaming, praising, and protecting our humanity: the implications of everyday
      dehumanization for judgments of moral status.
AB  - Being human implies a particular moral status: having moral value, agency, and
      responsibility. However, people are not seen as equally human. Across two
      studies, we examine the consequences that subtle variations in the perceived
      humanness of actors or groups have for their perceived moral status. Drawing on
      Haslam's two-dimensional model of humanness and focusing on three ways people may
      be considered to have moral status - moral patiency (value), agency, or
      responsibility - we demonstrate that subtly denying humanness to others has
      implications for whether they are blamed, praised, or considered worthy of moral
      concern and rehabilitation. Moreover, we show that distinct human characteristics
      are linked to specific judgments of moral status. This work demonstrates that
      everyday judgments of moral status are influenced by perceptions of humanness.

PMID- 21884546
TI  - Is the world a just place? Countering the negative consequences of pervasive
      discrimination by affirming the world as just.
AB  - Two studies (a) explored the role of pervasiveness of discrimination (pervasive
      vs. rare) in determining targets' responses to discrimination, and (b) examined
      the extent to which threats to participants' worldview can account, in part, for
      detrimental effects of pervasive discrimination. As predicted, across both
      studies, pervasiveness of discrimination moderated the relationship between
      attributions to prejudice for failure to obtain a job and psychological well
      being (depressed affect and state self-esteem). When discrimination was presented
      as pervasive, attributions to prejudice related to lower state self-esteem and
      greater depressed affect. When discrimination was portrayed as rare, attributions
      to prejudice were related to higher state self-esteem and unrelated to depressed
      affect. Study 2 further showed that being able to affirm the world as just
      countered the negative consequences of pervasive discrimination, whereas it did
      not influence responses to discrimination that was perceived as rare.

PMID- 21884547
TI  - Prime and prejudice: co-occurrence in the culture as a source of automatic
      stereotype priming.
AB  - It has been argued that stereotype priming (response times are faster for
      stereotypical word pairs, such as black-poor, than for non-stereotypical word
      pairs, such as black-balmy) is partially a function of biases in the belief
      system inherent in the culture. In three priming experiments, we provide direct
      evidence for this position, showing that stereotype priming effects associated
      with race, gender, and age can be very well explained through objectively
      measured associative co-occurrence of prime and target in the culture: (a) once
      objective associative strength between word pairs is taken into account,
      stereotype priming effects disappear; (b) the relationship between response time
      and associative strength is identical for social primes and non-social primes.
      The correlation between associative-value-controlled stereotype priming and self
      report measures of racism, sexism, and ageism is near zero. The
      racist/sexist/ageist in all of us appears to be (at least partially) a reflection
      of the surrounding culture.

PMID- 21884548
TI  - Do sexist organizational cultures create the Queen Bee?
AB  - 'Queen Bees' are senior women in masculine organizational cultures who have
      fulfilled their career aspirations by dissociating themselves from their gender
      while simultaneously contributing to the gender stereotyping of other women. It
      is often assumed that this phenomenon contributes to gender discrimination in
      organizations, and is inherent to the personalities of successful career women.
      We argue for a social identity explanation and examine organizational conditions
      that foster the Queen Bee phenomenon. Participants were 94 women holding senior
      positions in diverse companies in The Netherlands who participated in an on-line
      survey. In line with predictions, indicators of the Queen Bee phenomenon
      (increased gender stereotyping and masculine self-descriptions) were found mostly
      among women who indicated they had started their career with low gender
      identification and who had subsequently experienced a high degree of gender
      discrimination on their way up. By contrast, the experience of gender
      discrimination was unrelated to signs of the Queen Bee phenomenon among women who
      indicated to be highly identified when they started their career. Results are
      discussed in light of social identity theory, interpreting the Queen Bee
      phenomenon as an individual mobility response of low gender identified women to
      the gender discrimination they encounter in their work.

PMID- 21884550
TI  - Tryptamine 5-hydroxylase-deficient Sekiguchi rice induces synthesis of 5
      hydroxytryptophan and N-acetyltryptamine but decreases melatonin biosynthesis
      during senescence process of detached leaves.
AB  - Melatonin biosynthesis was examined in Sekiguchi mutant rice lacking functional
      tryptamine 5-hydroxylase (T5H) activity, which is the terminal enzyme for
      serotonin biosynthesis in rice. During senescence process, the leaves of
      Sekiguchi mutant rice produced more tryptamine and N-acetyltryptamine compared
      with the wild-type Asahi leaves. Even though T5H activity is absent, Sekiguchi
      leaves produce low levels of serotonin derived from 5-hydroxytryptophan, which
      was found to be synthesized during senescence process. Accordingly, both rice
      cultivars exhibited similar levels of N-acetylserotonin until 6 days of
      senescence induction; however, only Asahi leaves continued to accumulate N
      acetylserotonin after 6 days. In contrast, a large amount of N-acetyltryptamine
      was accumulated in Sekiguchi leaves, indicating that tryptamine was efficiently
      utilized as substrate by the rice arylalkylamine N-acetyltransferase enzyme. An
      increase in N-acetyltryptamine in Sekiguchi had an inhibitory effect on synthesis
      of melatonin because little melatonin was produced in Sekiguchi leaves at 6 days
      of senescence induction, even in the presence of equivalent levels of N
      acetylserotonin in both cultivars. The exogenous treatment of 0.1 mmN
      acetyltryptamine during senescence process completely blocked melatonin
      synthesis.

PMID- 21884551
TI  - Extrapineal melatonin: analysis of its subcellular distribution and daily
      fluctuations.
AB  - We studied the subcellular levels of melatonin in cerebral cortex and liver of
      rats under several conditions. The results show that melatonin levels in the cell
      membrane, cytosol, nucleus, and mitochondrion vary over a 24-hr cycle, although
      these variations do not exhibit circadian rhythms. The cell membrane has the
      highest concentration of melatonin followed by mitochondria, nucleus, and
      cytosol. Pinealectomy significantly increased the content of melatonin in all
      subcellular compartments, whereas luzindole treatment had little effect on
      melatonin levels. Administration of 10 mg/kg bw melatonin to sham
      pinealectomized, pinealectomized, or continuous light-exposed rats increased the
      content of melatonin in all subcellular compartments. Melatonin in doses ranging
      from 40 to 200 mg/kg bw increased in a dose-dependent manner the accumulation of
      melatonin on cell membrane and cytosol, although the accumulations were 10 times
      greater in the former than in the latter. Melatonin levels in the nucleus and
      mitochondria reached saturation with a dose of 40 mg/kg bw; higher doses of
      injected melatonin did not further cause additional accumulation of melatonin in
      these organelles. The results suggest some control of extrapineal accumulation or
      extrapineal production of melatonin and support the existence of regulatory
      mechanisms in cellular organelles, which prevent the intracellular equilibration
      of the indolamine. Seemingly, different concentrations of melatonin can be
      maintained in different subcellular compartments. The data also seem to support a
      requirement of high doses of melatonin to obtain therapeutic effects. Together,
      these results add information that assists in explaining the physiology and
      pharmacology of melatonin.

PMID- 21884552
TI  - Donor heparinization is not a contraindication to liver transplantation even in
      recipients with acute heparin-induced thrombocytopenia type II: a case report and
      review of the literature.
AB  - Heparin-induced thrombocytopenia (HIT) type II is caused by an immune-mediated
      side effect of heparin anticoagulation resulting in a clotting disorder. In the
      setting of urgent liver transplantation, the question arises whether a graft from
      a heparinized donor can be safely transplantated in a recipient with even acute
      heparin-induced thrombocytopenia type II. We report on a patient with end-stage
      liver disease and acute HIT II waiting for liver transplantation. Despite the
      risk of life-threatening complications, an organ procured from a heparinized
      donor was accepted. Assuming heparin residuals within the graft, the donor organ
      was flushed backtable with increased amounts of Wisconsin solution. The
      subsequent transplantation and the postoperative course were uneventful; neither
      thromboses nor graft dysfunction occurred. Even in acute episode of HIT II with
      circulating antibodies, a patient may receive an organ from a heparin-treated
      donor, if adequate precautions during organ preparation are observed.

PMID- 21884553
TI  - Cholangiocarcinoma complicating recurrent primary sclerosing cholangitis after
      liver transplantation.
AB  - De novo cholangiocarcinoma associated with recurrent primary sclerosing
      cholangitis in the transplanted liver is rare. This case report reviews the
      literature and highlights the need to consider cholangiocarcinoma in transplanted
      patients with PSC that clinically/biochemically deteriorate.

PMID- 21884554
TI  - Recovery after chronic stress within spatial reference and working memory
      domains: correspondence with hippocampal morphology.
AB  - Chronic stress results in reversible spatial learning impairments in the Morris
      water maze that correspond with hippocampal CA3 dendritic retraction in male
      rats. Whether chronic stress impacts different types of memory domains, and
      whether these can similarly recover, is unknown. This study assessed the effects
      of chronic stress with and without a post-stress delay to evaluate learning and
      memory deficits within two memory domains, reference and working memory, in the
      radial arm water maze (RAWM). Three groups of 5-month-old male Sprague-Dawley
      rats were either not stressed [control (CON)], or restrained (6 h/day for 21
      days) and then tested on the RAWM either on the next day [stress immediate (STR
      IMM)] or following a 21-day delay [stress delay (STR-DEL)]. Although the groups
      learned the RAWM task similarly, groups differed in their 24-h retention trial
      assessment. Specifically, the STR-IMM group made more errors within both the
      spatial reference and working memory domains, and these deficits corresponded
      with a reduction in apical branch points and length of hippocampal CA3 dendrites.
      In contrast, the STR-DEL group showed significantly fewer errors in both the
      reference and working memory domains than the STR-IMM group. Moreover, the STR
      DEL group showed better RAWM performance in the reference memory domain than did
      the CON group, and this corresponded with restored CA3 dendritic complexity,
      revealing long-term enhancing actions of chronic stress. These results indicate
      that chronic stress-induced spatial working and reference memory impairments, and
      CA3 dendritic retraction, are reversible, with chronic stress having lasting
      effects that can benefit spatial reference memory, but with these lasting
      beneficial effects being independent of CA3 dendritic complexity.

PMID- 21884555
TI  - Middle-aged, but not young, rats develop cognitive impairment and cortical
      neurodegeneration following the four-vessel occlusion/internal carotid artery
      model of chronic cerebral hypoperfusion.
AB  - Permanent, stepwise occlusion of the vertebral arteries (VAs) and internal
      carotid arteries (ICAs) following the sequence VA->ICA->ICA, with an interstage
      interval (ISI, ->) of 7 days, has been investigated as a four-vessel occlusion (4
      VO)/ICA model of chronic cerebral hypoperfusion. This model has the advantage of
      not causing retinal damage. In young rats, however, 4-VO/ICA with an ISI of 7
      days fails to cause behavioral sequelae. We hypothesized that such a long ISI
      would allow the brain to efficiently compensate for cerebral hypoperfusion,
      preventing the occurrence of cognitive impairment and neurodegeneration. The
      present study evaluated whether brain neurodegeneration and learning/memory
      deficits can be expressed by reducing the length of the ISI and whether aging
      influences the outcome. Young, male Wistar rats were subjected to 4-VO/ICA with
      different ISIs (5, 4, 3 or 2 days). An ISI of 4 days was used in middle-aged
      rats. Ninety days after 4-VO/ICA, the rats were tested for learning/memory
      impairment in a modified radial maze and then examined for neurodegeneration of
      the hippocampus and cerebral cortex. Regardless of the ISI, young rats were not
      cognitively impaired, although hippocampal damage was evident. Learning/memory
      deficits and hippocampal and cortical neurodegeneration occurred in middle-aged
      rats. The data indicate that 4-VO/ICA has no impact on the capacity of young rats
      to learn the radial maze task, despite 51% hippocampal cell death. Such
      resistance is lost in middle-aged animals, for which the most extensive
      neurodegeneration observed in both the hippocampus and cerebral cortex may be
      responsible.

PMID- 21884556
TI  - Moral distress and ethical climate in a Swedish nursing context: perceptions and
      instrument usability.
AB  - AIMS AND OBJECTIVES: The aim was fivefold: to describe Swedish nurses'
      perceptions of moral distress and determine whether there were differences in
      perceptions depending on demographic characteristics and to describe the
      usability of the Moral Distress Scale in a Swedish context. Further, the aim was
      to describe Swedish nurses' perceptions of ethical climate and the relationship
      between moral distress and ethical climate. BACKGROUND: Moral distress has been
      studied for more than two decades and the Moral Distress Scale is the most widely
      used instrument for measuring it. Moral distress has mainly been studied in
      relation to nurses' characteristics, but increasing attention has been paid to
      contextual aspects, such as ethical climate, that could be associated with moral
      distress. DESIGN: Descriptive, with a quantitative approach. METHODS: The study
      used two questionnaires: the Moral Distress Scale and the Hospital Ethical
      Climate Survey. The study was carried out at two hospitals in Sweden and included
      249 nurses. RESULTS: Both level and frequency of moral distress were low, however
      level of moral distress was high in situations when the patient was not given
      safe and proper care. Generally, the frequency of moral distress was lower than
      the level. Of the situations on the Moral Distress Scale, 13 of the 32 were
      considered irrelevant by 10-50% of the participants. The more positive the
      ethical climate was perceived to be, the less frequently morally distressing
      situations were reported. CONCLUSIONS: Since a positive ethical climate was
      associated with less frequent occurrences of moral distress, it should be
      investigated what contributes to a positive ethical climate. To be used in a
      Swedish context, the Moral Distress Scale needs further revision. RELEVANCE TO
      CLINICAL PRACTICE: Open dialogues at wards are encouraged regarding what
      practices contribute to a positive ethical climate.

PMID- 21884557
TI  - Managing blood glucose during and after exercise in Type 1 diabetes:
      reproducibility of glucose response and a trial of a structured algorithm
      adjusting insulin and carbohydrate intake.
AB  - AIMS AND OBJECTIVES: To enable people with Type 1 diabetes to exercise safely by
      investigating the reproducibility of the glucose response to an algorithm for
      carbohydrate and insulin adjustment during and after exercise compared to their
      self-management strategies. BACKGROUND: Difficulties in managing blood glucose
      levels in Type 1 diabetes whilst exercising is known to deter people from
      exercise. Currently there is a limited evidence base to aid health care
      professionals enable people with diabetes to exercise safely. This study seeks to
      address this gap. DESIGN: A quasi-experimental study was undertaken amongst
      people with Type 1 diabetes. METHODS: Over 14 days, 14 participants undertook
      four exercise sessions (40 minutes at 50%VO2max). Two sessions were undertaken in
      week 1 self-managing their diabetes and two sessions in week 2 using an algorithm
      for carbohydrate and insulin adjustment. RESULTS: The mean reduction of glucose
      levels detected by Continuous Glucose Monitoring during exercise was 3.1 (SD
      2.03) mmol/l. Time spent within the range of 4-9 mmol/l during exercise was not
      significantly different between the self-managed and the algorithm weeks (-3-22.4
      min). The mean reduction of blood glucose for each individual over all four
      exercise sessions ranged between 0.8-5.95 mmol/l. The technical error between
      days one and two was 2.4 mmol/l (CV=33.2%) and between days 3-4 the technical
      error was 2.7 mmol/l (CV=33.7%). CONCLUSIONS: The results provide useful data
      about the reproducibility of the blood glucose response to moderate intensity
      exercise, despite the variability of individual responses 40 minutes of moderate
      intensity exercise decreases Continuous Glucose Monitoring glucose by 3 mmol/l
      with or without a 30% decrease of insulin before exercise. RELEVANCE TO CLINICAL
      PRACTICE: This information provides valuable baseline information for people with
      diabetes and health care professionals who wish to encourage physical activity
      and undertake further research in this area.

PMID- 21884559
TI  - Beliefs about health and illness in Swedish and African-born women with
      gestational diabetes living in Sweden.
AB  - AIMS: This paper is a report on a study exploring beliefs about health and
      illness in women with gestational diabetes born in Sweden and Africa living in
      Sweden. A further aim is to study the influence of beliefs on self-care and care
      seeking. BACKGROUND: Extensive global migration leading to multicultural
      societies implies challenges to health care. Health/illness beliefs are
      culturally related and determine health-related behaviour, including self-care,
      which is crucial in management of gestational diabetes. The risk of developing
      gestational diabetes is increased in migrants, particularly of African origin,
      when residing in Western countries. No previous studies, except one, have been
      found comparing health/illness beliefs in women with gestational diabetes of
      different origin. DESIGN: Exploratory descriptive study. METHODS: Semi-structured
      interviews. Consecutive sample of women diagnosed with gestational diabetes, 13
      born in Sweden and 10 born in Africa, from a diabetes clinic in Sweden.
      Qualitative content analysis of data was applied. RESULTS: Beliefs were mainly
      related to individual and social factors. Health was described as freedom from
      disease and being healthy. Swedish women perceived heredity and hormonal changes
      as causing gestational diabetes, avoided work-related stress, had a healthy
      lifestyle, worried about the baby's health and development of type 2 diabetes,
      sought information, used more medications and health care and were on sick-leave
      more often because of pregnancy-related problems than African women, who did not
      know the cause of gestational diabetes, had a passive self-care attitude and
      followed prescriptions, often reported being told by staff that gestational
      diabetes would disappear after delivery and stated more pregnancy-related
      problems which they treated with rest or watchful waiting. CONCLUSIONS:
      Health/illness beliefs differed and affected self-care and care seeking. Lower
      risk awareness in African-born women was related to limited knowledge about the
      body and gestational diabetes, which was further amplified by healthcare
      professionals informing them about gestational diabetes being transient.
      RELEVANCE TO CLINICAL PRACTICE: Individual beliefs and risk awareness must be
      elicited, and adequate information must be given to prevent negative health
      effects of gestational diabetes.

PMID- 21884558
TI  - Patients' and nurses' perceptions of individualised care: an international
      comparative study.
AB  - AIM: The aim of this study was to compare patients' and nurses' perceptions of
      individualised care in five European countries, the Czech Republic, Cyprus,
      Finland, Greece and Hungary. BACKGROUND: Individualised nursing care has been
      studied from both patients' and nurses' perspectives, but to date, there are no
      studies comparing these perspectives internationally. METHODS: A cross-sectional
      comparative survey design was used. Data were collected from nurses (n = 960;
      response rate, 79%) and patients (n = 1315; response rate, 78%) in 71 surgical
      units from 26 acute hospitals in 2009. Data were collected using two
      Individualised Care Scales (ICS-Nurse and ICS-Patient) and analysed statistically
      using descriptive and inferential statistics. RESULTS: Differences in patients'
      and nurses' assessments of individualised nursing care were found between each
      country. Nurses, compared with patients, assessed that they supported patient
      individuality more often. The Mean(nurses) ranged from 3.61 (SD 0.90, Greece)
      4.31 (SD 0.53, Hungary), and the Mean(patients) ranged from 3.05 (SD 1.09,
      Greece)-3.79 (SD 1.00, Cyprus). To a large extent, the care provided was
      individualised as defined by the Mean(nurses) 3.75 (SD 0.92, Greece)-4.36 (SD
      0.49, Hungary) and the Mean(patients) 3.41 (SD 0.95, Greece)-4.18 (SD 0.79,
      Cyprus). In Cyprus and Finland, patients' assessments of the individuality in
      their care corresponded well with nurses' assessments. Clear between-country
      differences in both patients' and nurses' assessments were found in both
      subscales of the ICS. CONCLUSIONS: An in-depth analysis of the European between
      country differences is required to define the causes of differences that may be
      due to the differing content of education, the organisation of nursing work,
      ideology and values assigned to individualised care and health care systems and
      processes in each country. RELEVANCE TO CLINICAL PRACTICE: Obtaining both
      patients' and nurses' assessments of individualised care may facilitate the
      further development of individualised nursing care and be used to help to
      harmonise European health care processes and nursing care.

PMID- 21884562
TI  - The use of leptin as treatment for type 1 diabetes mellitus: counterpoint.

PMID- 21884563
TI  - Forest species diversity reduces disease risk in a generalist plant pathogen
      invasion.
AB  - Empirical evidence suggests that biodiversity loss can increase disease
      transmission, yet our understanding of the 'diversity-disease hypothesis' for
      generalist pathogens in natural ecosystems is limited. We used a landscape
      epidemiological approach to examine two scenarios regarding diversity effects on
      the emerging plant pathogen Phytophthora ramorum across a broad, heterogeneous
      ecoregion: (1) an amplification effect exists where disease risk is greater in
      areas with higher plant diversity due to the pathogen's wide host range, or (2) a
      dilution effect where risk is reduced with increasing diversity due to lower
      competency of alternative hosts. We found evidence for pathogen dilution, whereby
      disease risk was lower in sites with higher species diversity, after accounting
      for potentially confounding effects of host density and landscape heterogeneity.
      Our results suggest that although nearly all plants in the ecosystem are hosts,
      alternative hosts may dilute disease transmission by competent hosts, thereby
      buffering forest health from infectious disease.

PMID- 21884564
TI  - Malignant pheochromocytoma presenting as incapacitating bony pain.
AB  - Among adrenal incidentalomas, pheochromocytomas are rare. Malignant
      pheochromocytoma is even less common, and it typically presents with classic
      hormonal symptoms, such as palpitations, labile blood pressures, and headaches.
      Bony metastasis usually occurs late in disease, but we report an unusual case of
      incapacitating bony pain as the initial presentation of malignant
      pheochromocytoma. Our patient is a 70-year-old woman with neurofibromatosis type
      1 and a history of primary hyperparathyroidism, who tested negative for the ret
      mutation. She came to medical attention with chest pain and palpitations and was
      incidentally found to have an adrenal mass. Serum and urine testing was
      consistent with pheochromocytoma. Her blood pressure was easily controlled as she
      awaited elective adrenalectomy; however, she quickly developed severe, diffuse
      bony pain. She represented with hypercalcemia, spontaneous fractures, and
      incapacitating pain that required such high doses of pain medications that she
      had to be intubated. Further imaging and bone marrow biopsy confirmed metastatic
      neuroendocrine tumor. She received one round of chemotherapy with no change in
      her bony pain, which was her primary complaint. Unfortunately, her treatment
      options were limited by the heavy sedation required for comfort, and in the end,
      it was her bony pain rather than hormonal symptoms that made her disease
      untreatable.

PMID- 21884565
TI  - Definition of clinical efficacy and safety outcomes for clinical trials in deep
      venous thrombosis and pulmonary embolism in children.

PMID- 21884566
TI  - Towards a recommendation for the standardization of the measurement of platelet
      dependent thrombin generation.

PMID- 21884567
TI  - Towards a standardization of the murine ferric chloride-induced carotid arterial
      thrombosis model.

PMID- 21884568
TI  - Characterization of the PLP-dependent aminotransferase NikK from Streptomyces
      tendae and its putative role in nikkomycin biosynthesis.
AB  - As inhibitors of chitin synthase, nikkomycins have attracted interest as
      potential antibiotics. The biosynthetic pathway to these peptide nucleosides in
      Streptomyces tendae is only partially known. In order to elucidate the last step
      of the biosynthesis of the aminohexuronic building block, we have heterologously
      expressed a predicted aminotransferase encoded by the gene nikK from S. tendae in
      Escherichia coli. The purified protein, which is essential for nikkomycin
      biosynthesis, has a pyridoxal-5'-phosphate cofactor bound as a Schiff base to
      lysine 221. The enzyme possesses aminotransferase activity and uses several
      standard amino acids as amino group donors with a preference for glutamate (Glu >
      Phe > Trp > Ala > His > Met > Leu). Therefore, we propose that NikK catalyses the
      introduction of the amino group into the ketohexuronic acid precursor of
      nikkomycins. At neutral pH, the UV-visible absorbance spectrum of NikK has two
      absorbance maxima at 357 and 425 nm indicative of the presence of the
      deprotonated and protonated aldimine with an estimated pK(a) of 8.3. The rate of
      donor substrate deamination is faster at higher pH, indicating that an alkaline
      environment favours the deamination reaction.

PMID- 21884569
TI  - Microenvironmental genomic alterations reveal signaling networks for head and
      neck squamous cell carcinoma.
AB  - BACKGROUND: Advanced stage head and neck squamous cell carcinoma (HNSCC) is an
      aggressive cancer with low survival rates. Loss-of-heterozygosity/allelic
      imbalance (LOH/AI) analysis has been widely used to identify genomic alterations
      in solid tumors and the tumor microenvironment (stroma). We hypothesize that
      these identified alterations can point to signaling networks functioning in HNSCC
      epithelial-tumor and surrounding stroma (tumor microenvironment). RESULTS: Under
      the assumption that genes in proximity to identified LOH/AI regions are
      correlated with the tumorigenic phenotype, we mined publicly available biological
      information to identify pathway segments (signaling proteins connected to each
      other in a network) and identify the role of tumor microenvironment in HNSCC.
      Across both neoplastic epithelial cells and the surrounding stromal cells,
      genetic alterations in HNSCC were successfully identified, and 75 markers were
      observed to have significantly different LOH/AI frequencies in these compartments
      (p < 0.026). We applied a network identification approach to the genes in
      proximity to these 75 markers in cancer epithelium and stroma in order to
      identify biological networks that can describe functional associations amongst
      these marker-associated genes. CONCLUSIONS: We verified the involvement of T-cell
      receptor signaling pathways in HNSCC as well as associated oncogenes such as LCK
      and PLCB1, and tumor suppressors such as STAT5A, PTPN6, PARK2. We identified
      expression levels of genes within significant LOH/AI regions specific to stroma
      networks that correlate with better outcome in radiation therapy. By integrating
      various levels of high-throughput data, we were able to precisely focus on
      specific proteins and genes that are germane to HNSCC.

PMID- 21884570
TI  - Leveraging a clinical research information system to assist biospecimen data and
      workflow management: a hybrid approach.
AB  - BACKGROUND: Large multi-center clinical studies often involve the collection and
      analysis of biological samples. It is necessary to ensure timely, complete and
      accurate recording of analytical results and associated phenotypic and clinical
      information. The TRIBE-AKI Consortium http://www.yale.edu/tribeaki supports a
      network of multiple related studies and sample biorepository, thus allowing
      researchers to take advantage of a larger specimen collection than they might
      have at an individual institution. DESCRIPTION: We describe a biospecimen data
      management system (BDMS) that supports TRIBE-AKI and is intended for multi-center
      collaborative clinical studies that involve shipment of biospecimens between
      sites. This system works in conjunction with a clinical research information
      system (CRIS) that stores the clinical data associated with the biospecimens,
      along with other patient-related parameters. Inter-operation between the two
      systems is mediated by an interactively invoked suite of Web Services, as well as
      by batch code. We discuss various challenges involved in integration.
      CONCLUSIONS: Our experience indicates that an approach that emphasizes inter
      operability is reasonably optimal in allowing each system to be utilized for the
      tasks for which it is best suited.

PMID- 21884571
TI  - Genomic analysis and temperature-dependent transcriptome profiles of the
      rhizosphere originating strain Pseudomonas aeruginosa M18.
AB  - BACKGROUND: Our previously published reports have described an effective
      biocontrol agent named Pseudomonas sp. M18 as its 16S rDNA sequence and several
      regulator genes share homologous sequences with those of P. aeruginosa, but there
      are several unusual phenotypic features. This study aims to explore its strain
      specific genomic features and gene expression patterns at different temperatures.
      RESULTS: The complete M18 genome is composed of a single chromosome of 6,327,754
      base pairs containing 5684 open reading frames. Seven genomic islands, including
      two novel prophages and five specific non-phage islands were identified besides
      the conserved P. aeruginosa core genome. Each prophage contains a putative
      chitinase coding gene, and the prophage II contains a capB gene encoding a
      putative cold stress protein. The non-phage genomic islands contain genes
      responsible for pyoluteorin biosynthesis, environmental substance degradation and
      type I and III restriction-modification systems. Compared with other P.
      aeruginosa strains, the fewest number (3) of insertion sequences and the most
      number (3) of clustered regularly interspaced short palindromic repeats in M18
      genome may contribute to the relative genome stability. Although the M18 genome
      is most closely related to that of P. aeruginosa strain LESB58, the strain M18 is
      more susceptible to several antimicrobial agents and easier to be erased in a
      mouse acute lung infection model than the strain LESB58. The whole M18
      transcriptomic analysis indicated that 10.6% of the expressed genes are
      temperature-dependent, with 22 genes up-regulated at 28 degrees C in three non
      phage genomic islands and one prophage but none at 37 degrees C. CONCLUSIONS: The
      P. aeruginosa strain M18 has evolved its specific genomic structures and
      temperature dependent expression patterns to meet the requirement of its fitness
      and competitiveness under selective pressures imposed on the strain in
      rhizosphere niche.

PMID- 21884572
TI  - Pegylated interferon-alfa-2a monotherapy in patients infected with HCV genotype 2
      and importance of rapid virological response.
AB  - BACKGROUND: Pegylated (PEG)-interferon (IFN)-alfa-2a plus ribavirin (RBV) therapy
      for 24 weeks is now a standard treatment protocol for patients with hepatitis C
      virus (HCV) genotype 2. As RBV cannot be used in certain situations, we examined
      whether PEG-IFN-alfa-2a monotherapy for 24 weeks or less would be sufficient to
      obtain a sustained virological response (SVR) in patients infected with HCV
      genotype 2. METHODS: Forty-nine consecutive patients with HCV genotype 2 received
      PEG-IFN-alfa-2a (180 MUg/week) subcutaneously without oral RBV for 8-64 weeks.
      HCV RNA level was determined by COBAS AMPLICOR HCV Test, v2.0. RESULTS: HCV RNA
      was equal to or less than 100 KIU/mL (defined as low viral load) in 15 of 49
      patients, and the remaining 34 had HCV RNA above 100 KIU/mL (defined as high
      viral load). All 15 patients with low viral load achieved rapid virological
      response (RVR; HCV RNA negative at week 4), and also achieved SVR with an average
      treatment duration of 17.1 weeks. The 34 patients with high viral load were
      treated for 33.7 weeks on average, and 19 of them (55.9%) achieved RVR. The SVR
      rates of these patients were significantly higher in those with RVR than without
      RVR (16/19 vs. 6/15 p = 0.0074). CONCLUSION: PEG-IFN-alfa-2a monotherapy for 24
      weeks or less might be sufficient to treat selected patients with HCV genotype 2,
      especially those with low viral load and becoming negative for HCV RNA by week 4
      of treatment.

PMID- 21884574
TI  - Dynamic cerebral autoregulation after intracerebral hemorrhage: A case-control
      study.
AB  - BACKGROUND: Dynamic cerebral autoregulation after intracerebral hemorrhage (ICH)
      remains poorly understood. We performed a case-control study to compare dynamic
      autoregulation between ICH patients and healthy controls. METHODS: Twenty-one
      patients (66 +/- 15 years) with early (< 72 hours) lobar or basal ganglia ICH
      were prospectively studied and compared to twenty-three age-matched controls (65
      +/- 9 years). Continuous measures of mean flow velocity (MFV) in the middle
      cerebral artery and mean arterial blood pressure (MAP) were obtained over 5 min.
      Cerebrovascular resistance index (CVRi) was calculated as the ratio of MAP to
      MFV. Dynamic cerebral autoregulation was assessed using transfer function
      analysis of spontaneous MAP and MFV oscillations in the low (0.03-0.15 Hz) and
      high (0.15-0.5 Hz) frequency ranges. RESULTS: The ICH group demonstrated higher
      CVRi compared to controls (ipsilateral: 1.91 +/- 1.01 mmHg.s.cm-1, p = 0.04;
      contralateral: 2.01 +/- 1.24 mmHg.s.cm-1, p = 0.04; vs. control: 1.42 +/- 0.45
      mmHg.s.cm-1). The ICH group had higher gains than controls in the low
      (ipsilateral: 1.33 +/- 0.58%/mmHg, p = 0.0005; contralateral: 1.47 +/-
      0.98%/mmHg, p = 0.004; vs. control: 0.82 +/- 0.30%/mmHg) and high (ipsilateral:
      2.11 +/- 1.31%/mmHg, p < 0.0001; contralateral: 2.14 +/- 1.49%/mmHg, p < 0.0001;
      vs. control: 0.66 +/- 0.26%/mmHg) frequency ranges. The ICH group also had higher
      coherence in the contralateral hemisphere than the control (ICH contralateral:
      0.53 +/- 0.38, p = 0.02; vs. control: 0.38 +/- 0.15) in the high frequency range.
      CONCLUSIONS: Patients with ICH had higher gains in a wide range of frequency
      ranges compared to controls. These findings suggest that dynamic cerebral
      autoregulation may be less effective in the early days after ICH. Further study
      is needed to determine the relationship between hematoma size and severity of
      autoregulation impairment.

PMID- 21884575
TI  - Fulfillment of the brazilian agenda of priorities in health research.
AB  - This commentary describes how the Brazilian Ministry of Health's (MoH) research
      support policy fulfilled the National Agenda of Priorities in Health Research
      (NAPHR). In 2003, the MoH started a democratic process in order to establish a
      priority agenda in health research involving investigators, health managers and
      community leaders. The Agenda was launched in 2004 and is guiding budget
      allocations in an attempt to reduce the gap between scientific knowledge and
      health practice and activities, aiming to contribute to improving Brazilian
      quality of life. Many strategies were developed, for instance: Cooperation
      Agreements between the Ministry of Health and the Ministry of Science and
      Technology; the decentralization of research support at state levels with the
      participation of local Health Secretariats and Science and Technology
      Institutions; Health Technology Assessment; innovation in neglected diseases;
      research networks and multicenter studies in adult, women's and children's
      health; cardiovascular risk in adolescents; clinical research and stem cell
      therapy. The budget allocated by the Ministry of Health and partners was
      expressive: US$419 million to support almost 3,600 projects. The three sub-agenda
      with the higher proportion of resources were "industrial health complex",
      "clinical research" and "communicable diseases", which are considered strategic
      for innovation and national development. The Southeast region conducted 40.5% of
      all projects and detained 59.7% of the resources, attributable to the
      concentration of the most traditional health research institutes and universities
      in the states of Sao Paulo and Rio de Janeiro. The second most granted region was
      the Northeast, which reflects the result of a governmental policy to integrate
      and modernize this densely populated area and the poorest region in the country.
      Although Brazil began the design and implementation of the NAPHR in 2003, it has
      done so in accordance with the 'good practice principles' recently published:
      inclusive process, information gathering, careful planning and funding policy,
      transparency and internal evaluation (an external independent evaluation is
      underway). The effort in guiding the health research policy has achieved and
      legitimated an unprecedented developmental spurt to support strategic health
      research. We believe this experience is valuable and applicable to other
      countries, but different settings and local political circumstances will
      determine the best course of action to follow.

PMID- 21884573
TI  - beta1 integrin mediates an alternative survival pathway in breast cancer cells
      resistant to lapatinib.
AB  - INTRODUCTION: The overexpression of human epidermal growth factor receptor (HER)
      2 in 20% of human breast cancers and its association with aggressive growth has
      led to widespread use of HER2-targeted therapies, such as trastuzumab (T) and
      lapatinib (L). Despite the success of these drugs, their efficacy is limited in
      patients whose tumors demonstrate de novo or acquired resistance to treatment.
      The beta1 integrin resides on the membrane of the breast cancer cell, activating
      several elements of breast tumor progression including proliferation and
      survival. METHODS: We developed a panel of HER2-overexpressing cell lines
      resistant to L, T, and the potent LT combination through long-term exposure and
      validated these models in 3D culture. Parental and L/T/LT-resistant cells were
      subject to HER2 and beta1 integrin inhibitors in 3D and monitored for 12 days,
      followed by quantification of colony number. Parallel experiments were conducted
      where cells were either stained for Ki-67 and Terminal deoxynucleotidyl
      transferase dUTP nick end labeling (TUNEL) or harvested for protein and analyzed
      by immunoblot. Results were subjected to statistical testing using analysis of
      variance and linear contrasts, followed by adjustment with the Sidak method.
      RESULTS: Using multiple cell lines including BT474 and HCC1954, we reveal that in
      L and LT resistance, where phosphorylation of EGFR/HER1, HER2, and HER3 are
      strongly inhibited, kinases downstream of beta1 integrin--including focal
      adhesion kinase (FAK) and Src--are up-regulated. Blockade of beta1 by the
      antibody AIIB2 abrogates this up-regulation and functionally achieves significant
      growth inhibition of L and LT resistant cells in 3D, without dramatically
      affecting the parental cells. SiRNA against beta1 as well as pharmacologic
      inhibition of FAK achieve the same growth inhibitory effect. In contrast,
      trastuzumab-resistant cells, which retain high levels of phosphorylated
      EGFR/HER1, HER2, and HER3, are only modestly growth-inhibited by AIIB2.
      CONCLUSIONS: Our data suggest that HER2 activity, which is suppressed in
      resistance involving L but not T alone, dictates whether beta1 mediates an
      alternative pathway driving resistance. Our findings justify clinical studies
      investigating the inhibition of beta1 or its downstream signaling moieties as
      strategies to overcome acquired L and LT resistance.

PMID- 21884576
TI  - Identification of improved IL28B SNPs and haplotypes for prediction of drug
      response in treatment of hepatitis C using massively parallel sequencing in a
      cross-sectional European cohort.
AB  - BACKGROUND: The hepatitis C virus (HCV) infects nearly 3% of the World's
      population, causing severe liver disease in many. Standard of care therapy is
      currently pegylated interferon alpha and ribavirin (PegIFN/R), which is effective
      in less than half of those infected with the most common viral genotype. Two
      IL28B single nucleotide polymorphisms (SNPs), rs8099917 and rs12979860, predict
      response to (PegIFN/R) therapy in treatment of HCV infection. These SNPs were
      identified in genome wide analyses using Illumina genotyping chips. In people of
      European ancestry, there are 6 common (more than 1%) haplotypes for IL28B, one
      tagged by the rs8099917 minor allele, four tagged by rs12979860. METHODS: We used
      massively parallel sequencing of the IL28B and IL28A gene regions generated by
      polymerase chain reaction (PCR) from pooled DNA samples from 100 responders and
      99 non-responders to therapy, to identify common variants. Variants that had high
      odds ratios and were validated were then genotyped in a cohort of 905 responders
      and non-responders. Their predictive power was assessed, alone and in combination
      with HLA-C. RESULTS: Only SNPs in the IL28B linkage disequilibrium block
      predicted drug response. Eighteen SNPs were identified with evidence for
      association with drug response, and with a high degree of confidence in the
      sequence call. We found that two SNPs, rs4803221 (homozygote minor allele
      positive predictive value (PPV) of 77%) and rs7248668 (PPV 78%), predicted
      failure to respond better than the current best, rs8099917 (PPV 73%) and
      rs12979860 (PPV 68%) in this cross-sectional cohort. The best SNPs tagged a
      single common haplotype, haplotype 2. Genotypes predicted lack of response better
      than alleles. However, combination of IL28B haplotype 2 carrier status with the
      HLA-C C2C2 genotype, which has previously been reported to improve prediction in
      combination with IL28B, provides the highest PPV (80%). The haplotypes present
      alternative putative transcription factor binding and methylation sites.
      CONCLUSIONS: Massively parallel sequencing allowed identification and comparison
      of the best common SNPs for identifying treatment failure in therapy for HCV.
      SNPs tagging a single haplotype have the highest PPV, especially in combination
      with HLA-C. The functional basis for the association may be due to altered
      regulation of the gene. These approaches have utility in improving diagnostic
      testing and identifying causal haplotypes or SNPs.

PMID- 21884577
TI  - Correlates of sunscreen use among high school students: a cross-sectional survey.
AB  - BACKGROUND: Adolescents put themselves at risk of later skin cancer development
      and accelerated photo-aging due to their high rates of ultraviolet radiation
      exposure and low rates of skin protection. The purpose of the current study was
      to determine which of the Integrative Model constructs are most closely
      associated with sunscreen use among high school students. METHODS: The current
      study of 242 high school students involved a survey based on the Integrative
      Model including demographic and individual difference factors, skin protection
      related beliefs and outcome evaluations, normative beliefs, self-efficacy,
      sunscreen cues and availability, intentions, and sunscreen use. Our analyses
      included multiple linear regressions and bootstrapping to test for mediation
      effects. RESULTS: Sunscreen use was significantly associated with female gender,
      greater skin sensitivity, higher perceived sunscreen benefits, higher skin
      protection importance, more favorable sunscreen user prototype, stronger skin
      protection norms, greater perceived skin protection behavioral control, and
      higher sunscreen self-efficacy. Intentions to use sunscreen mediated the
      relationships between most skin protection-related beliefs and sunscreen use.
      CONCLUSIONS: The current study identified specific variables that can be targeted
      in interventions designed to increase sunscreen use among adolescents.

PMID- 21884578
TI  - Anti-depressive effectiveness of olanzapine, quetiapine, risperidone and
      ziprasidone: a pragmatic, randomized trial.
AB  - BACKGROUND: Efficacy studies indicate anti-depressive effects of at least some
      second generation antipsychotics (SGAs). The Bergen Psychosis Project (BPP) is a
      24-month, pragmatic, industry-independent, randomized, head-to-head comparison of
      olanzapine, quetiapine, risperidone and ziprasidone in patients acutely admitted
      with psychosis. The aim of the study is to investigate whether differential anti
      depressive effectiveness exists among SGAs in a clinically relevant sample of
      patients acutely admitted with psychosis. METHODS: Adult patients acutely
      admitted to an emergency ward for psychosis were randomized to olanzapine,
      quetiapine, risperidone or ziprasidone and followed for up to 2 years.
      Participants were assessed repeatedly using the Positive and Negative Syndrome
      Scale-Depression factor (PANSS-D) and the Calgary Depression Scale for
      Schizophrenia (CDSS). RESULTS: A total of 226 patients were included. A
      significant time-effect showing a steady decline in depressive symptoms in all
      medication groups was demonstrated. There were no substantial differences among
      the SGAs in reducing the PANSS-D score or the CDSS sum score. Separate analyses
      of groups with CDSS sum scores > 6 or <=6, respectively, reflecting degree of
      depressive morbidity, revealed essentially identical results to the primary
      analyses. There was a high correlation between the PANSS-D and the CDSS sum score
      (r = 0.77; p < 0.01). CONCLUSIONS: There was no substantial difference in anti
      depressive effectiveness among olanzapine, quetiapine, risperidone or ziprasidone
      in this clinically relevant sample of patients acutely admitted to hospital for
      symptoms of psychosis. Based on our findings we can make no recommendations
      concerning choice of any particular SGA for targeting symptoms of depression in a
      patient acutely admitted with psychosis. TRIAL REGISTRATION: ClinicalTrials.gov
      ID; URL: http://www.clinicaltrials.gov/: NCT00932529.

PMID- 21884579
TI  - Rebranding exercise: closing the gap between values and behavior.
AB  - BACKGROUND: Behavior can only be understood by identifying the goals to which it
      is attached. Superordinate-level goals are linked to individuals' values, and may
      offer insights into how to connect exercise with their core values and increase
      participation in sustainable ways. METHODS: A random sample of healthy midlife
      women (aged 40-60y) was selected to participate in a year-long mixed-method study
      (n = 226). Superordinate goals were measured inductively and analyzed using
      grounded theory analysis. Attainment Value and Exercise Participation were
      quantitatively measured. An ANOVA and pairwise comparisons were conducted to
      investigate the differences between superordinate exercise goals in attainment
      value. This study fit a Linear Mixed Model to the data to investigate the fixed
      effects of superordinate goals on exercise participation, controlling for BMI and
      social support. RESULTS: Participants mainly exercised to achieve Healthy-Aging,
      Quality-of-Life, Current-Health, and Appearance/Weight superordinate goals.
      Despite equally valuing Healthy-Aging, Quality-of-Life, and Current-Health goals,
      participants with Quality-of-Life goals reported participating in more exercise
      than those with Current-Health (p < 0.01), and Healthy-Aging (p = 0.06) goals.
      CONCLUSIONS: Superordinate exercise goals related to health and healthy aging are
      associated with less exercise than those related to enhancing daily quality of
      life, despite being equally valued. While important, pursuing distant benefits
      from exercise such as health promotion, disease prevention, and longevity might
      not be as compelling to busy individuals compared to their other daily priorities
      and responsibilities. By shifting our paradigm from medicine to marketing, we can
      glean insights into how we can better market and "sell" exercise. Because
      immediate payoffs motivate behavior better than distant goals, a more effective
      "hook" for promoting sustainable participation might be to rebrand exercise as a
      primary way individuals can enhance the quality of their daily lives. These
      findings have important implications for how we as a culture, especially those in
      fitness-related businesses, health promotion, health care, and public health,
      prescribe and market exercise on individual and population levels.

PMID- 21884580
TI  - Inhibitory effects of the JAK inhibitor CP690,550 on human CD4(+) T lymphocyte
      cytokine production.
AB  - BACKGROUND: The new JAK3 inhibitor, CP690,550, has shown efficacy in the
      treatment of rheumatoid arthritis. The present study was undertaken to assess the
      effects of CP690,550 on cytokine production and cellular signaling in human
      CD4(+) T cells. RESULTS: CD4(+) T cells produced IL-2, IL-4, IL-17, IL-22 and IFN
      gamma in following stimulation with a CD3 antibody. At the optimal concentration,
      CP690,550 almost completely inhibited the production of IL-4, IL-17, IL-22 and
      IFN-gamma from these activated CD4(+) T cells, but only had marginal effects on
      IL-2 production. Moreover CP690,550 inhibited anti-CD3-induced phosphorylation of
      STAT1, STAT3, STAT4, STAT5, and STAT6, but not the TCR-associated phosphorylation
      of ZAP-70. CONCLUSIONS: Therefore, CP690,550-mediated modification of the
      JAK/STAT pathway may be a new immunosuppressive strategy in the treatment of
      autoimmune diseases.

PMID- 21884581
TI  - A fiber-modified adenoviral vector interacts with immunoevasion molecules of the
      B7 family at the surface of murine leukemia cells derived from dormant tumors.
AB  - Tumor cells can escape the immune system by overexpressing molecules of the B7
      family, e.g. B7-H1 (PD-L1 or CD86), which suppresses the anti-tumor T-cell
      responses through binding to the PD-1 receptor, and similarly for B7.1 (CD80),
      through binding to CTLA-4. Moreover, direct interactions between B7-H1 and B7.1
      molecules are also likely to participate in the immunoevasion mechanism. In this
      study, we used a mouse model of tumor dormancy, DA1-3b leukemia cells. We
      previously showed that a minor population of DA1-3b cells persists in equilibrium
      with the immune system for long periods of time, and that the levels of surface
      expression of B7-H1 and B7.1 molecules correlates with the dormancy time. We
      found that leukemia cells DA1-3b/d365 cells, which derived from long-term dormant
      tumors and overexpressed B7-H1 and B7.1 molecules, were highly permissive to
      Ad5FB4, a human adenovirus serotype 5 (Ad5) vector pseudotyped with chimeric
      human-bovine fibers. Both B7-H1 and B7.1 were required for Ad5FB4-cell binding
      and entry, since (i) siRNA silencing of one or the other B7 gene transcript
      resulted in a net decrease in the cell binding and Ad5FB4-mediated transduction
      of DA1-3b/d365; and (ii) plasmid-directed expression of B7.1 and B7-H1 proteins
      conferred to Ad5FB4-refractory human cells a full permissiveness to this vector.
      Binding data and flow cytometry analysis suggested that B7.1 and B7-H1 molecules
      played different roles in Ad5FB4-mediated transduction of DA1-3b/d365, with B7.1
      involved in cell attachment of Ad5FB4, and B7-H1 in Ad5FB4 internalization. BRET
      analysis showed that B7.1 and B7-H1 formed heterodimeric complexes at the cell
      surface, and that Ad5FB4 penton, the viral capsomere carrying the fiber
      projection, could negatively interfere with the formation of B7.1/B7-H1
      heterodimers, or modify their conformation. As interactors of B7-H1/B7.1
      molecules, Ad5FB4 particles and/or their penton capsomeres represent potential
      therapeutic agents targeting cancer cells that had developed immunoevasion
      mechanisms.

PMID- 21884582
TI  - Application of Celluspots peptide arrays for the analysis of the binding
      specificity of epigenetic reading domains to modified histone tails.
AB  - BACKGROUND: Epigenetic reading domains are involved in the regulation of gene
      expression and chromatin state by interacting with histones in a post
      translational modification specific manner. A detailed knowledge of the target
      modifications of reading domains, including enhancing and inhibiting secondary
      modifications, will lead to a better understanding of the biological signaling
      processes mediated by reading domains. RESULTS: We describe the application of
      Celluspots peptide arrays which contain 384 histone peptides carrying 59 post
      translational modifications in different combinations as an inexpensive, reliable
      and fast method for initial screening for specific interactions of reading
      domains with modified histone peptides. To validate the method, we tested the
      binding specificities of seven known epigenetic reading domains on Celluspots
      peptide arrays, viz. the HP1beta and MPP8 Chromo domains, JMJD2A and 53BP1 Tudor
      domains, Dnmt3a PWWP domain, Rag2 PHD domain and BRD2 Bromo domain. In general,
      the binding results agreed with literature data with respect to the primary
      specificity of the reading domains, but in almost all cases we obtained
      additional new information concerning the influence of secondary modifications
      surrounding the target modification. CONCLUSIONS: We conclude that Celluspots
      peptide arrays are powerful screening tools for studying the specificity of
      putative reading domains binding to modified histone peptides.

PMID- 21884583
TI  - Clustering with position-specific constraints on variance: applying redescending
      M-estimators to label-free LC-MS data analysis.
AB  - BACKGROUND: Clustering is a widely applicable pattern recognition method for
      discovering groups of similar observations in data. While there are a large
      variety of clustering algorithms, very few of these can enforce constraints on
      the variation of attributes for data points included in a given cluster. In
      particular, a clustering algorithm that can limit variation within a cluster
      according to that cluster's position (centroid location) can produce effective
      and optimal results in many important applications ranging from clustering of
      silicon pixels or calorimeter cells in high-energy physics to label-free liquid
      chromatography based mass spectrometry (LC-MS) data analysis in proteomics and
      metabolomics. RESULTS: We present MEDEA (M-Estimator with DEterministic
      Annealing), an M-estimator based, new unsupervised algorithm that is designed to
      enforce position-specific constraints on variance during the clustering process.
      The utility of MEDEA is demonstrated by applying it to the problem of "peak
      matching"--identifying the common LC-MS peaks across multiple samples--in
      proteomic biomarker discovery. Using real-life datasets, we show that MEDEA not
      only outperforms current state-of-the-art model-based clustering methods, but
      also results in an implementation that is significantly more efficient, and hence
      applicable to much larger LC-MS data sets. CONCLUSIONS: MEDEA is an effective and
      efficient solution to the problem of peak matching in label-free LC-MS data. The
      program implementing the MEDEA algorithm, including datasets, clustering results,
      and supplementary information is available from the author website at
      http://www.hephy.at/user/fru/medea/.

PMID- 21884584
TI  - The C242T polymorphism of the p22-phox gene (CYBA) is associated with higher left
      ventricular mass in Brazilian hypertensive patients.
AB  - BACKGROUND: Reactive oxygen species have been implicated in the
      physiopathogenesis of hypertensive end-organ damage. This study investigated the
      impact of the C242T polymorphism of the p22-phox gene (CYBA) on left ventricular
      structure in Brazilian hypertensive subjects. METHODS: We cross-sectionally
      evaluated 561 patients from 2 independent centers [Campinas (n = 441) and Vitoria
      (n = 120)] by clinical history, physical examination, anthropometry, analysis of
      metabolic and echocardiography parameters as well as p22-phox C242T polymorphism
      genotyping. In addition, NADPH-oxidase activity was quantified in peripheral
      mononuclear cells from a subgroup of Campinas sample. RESULTS: Genotype
      frequencies in both samples were consistent with the Hardy- Weinberg equilibrium.
      Subjects with the T allele presented higher left ventricular mass/height2.7 than
      those carrying the CC genotype in Campinas (76.8 +/- 1.6 vs 70.9 +/- 1.4 g/m2.7;
      p = 0.009), and in Vitoria (45.6 +/- 1.9 vs 39.9 +/- 1.4 g/m2.7; p = 0.023)
      samples. These results were confirmed by stepwise regression analyses adjusted
      for age, gender, blood pressure, metabolic variables and use of anti-hypertensive
      medications. In addition, increased NADPH-oxidase activity was detected in
      peripheral mononuclear cells from T allele carriers compared with CC genotype
      carriers (p = 0.03). CONCLUSIONS: The T allele of the p22-phox C242T polymorphism
      is associated with higher left ventricular mass/height 2.7 and increased NADPH
      oxidase activity in Brazilian hypertensive patients. These data suggest that
      genetic variation within NADPH-oxidase components may modulate left ventricular
      remodeling in subjects with systemic hypertension.

PMID- 21884585
TI  - NF-kappaB activation within macrophages leads to an anti-tumor phenotype in a
      mammary tumor lung metastasis model.
AB  - INTRODUCTION: Metastasis from primary tumor to the lungs is a major cause of the
      mortality associated with breast cancer. Both immune and inflammatory responses
      impact whether circulating mammary tumor cells successfully colonize the lungs
      leading to established metastases. Nuclear factor -kappaB (NF-kappaB)
      transcription factors regulate both immune and inflammatory responses mediated in
      part by the activities of macrophages. Therefore, NF-kappaB activity specifically
      within macrophages may be a critical determinant of whether circulating tumor
      cells successfully colonize the lungs. METHODS: To investigate NF-kappaB
      signaling within macrophages during metastasis, we developed novel inducible
      transgenic models which target expression of the reverse tetracycline
      transactivator (rtTA) to macrophages using the cfms promoter in combination with
      inducible transgenics that express either an activator (cIKK2) or an inhibitor
      (IkappaBalpha-DN). Doxycyline treatment led to activation or inhibition of NF
      kappaB within macrophages. We used a tail vein metastasis model with mammary
      tumor cell lines established from MMTV-Polyoma Middle T-Antigen-derived tumors to
      investigate the effects of modulating NF-kappaB in macrophages during different
      temporal windows of the metastatic process. RESULTS: We found that activation of
      NF-kappaB in macrophages during seeding leads to a reduction in lung metastases.
      The mechanism involved expression of inflammatory cytokines and reactive oxygen
      species, leading to apoptosis of tumor cells and preventing seeding in the lung.
      Activation of NF-kappaB within macrophages after the seeding phase has no
      significant impact on establishment of metastases. CONCLUSIONS: Our results have
      identified a brief, defined window in which activation of NF-kappaB has
      significant anti-metastatic effects and inhibition of NF-kappaB results in a
      worse outcome.

PMID- 21884586
TI  - Over-expressing the C(3) photosynthesis cycle enzyme Sedoheptulose-1-7
      Bisphosphatase improves photosynthetic carbon gain and yield under fully open air
      CO(2) fumigation (FACE).
AB  - BACKGROUND: Biochemical models predict that photosynthesis in C(3) plants is most
      frequently limited by the slower of two processes, the maximum capacity of the
      enzyme Rubisco to carboxylate RuBP (V(c,max)), or the regeneration of RuBP via
      electron transport (J). At current atmospheric [CO(2)] levels Rubisco is not
      saturated; consequently, elevating [CO(2)] increases the velocity of
      carboxylation and inhibits the competing oxygenation reaction which is also
      catalyzed by Rubisco. In the future, leaf photosynthesis (A) should be
      increasingly limited by RuBP regeneration, as [CO(2)] is predicted to exceed 550
      ppm by 2050. The C(3) cycle enzyme sedoheptulose-1,7 bisphosphatase (SBPase, EC
      3.1.3.17) has been shown to exert strong metabolic control over RuBP regeneration
      at light saturation. RESULTS: We tested the hypothesis that tobacco transformed
      to overexpressing SBPase will exhibit greater stimulation of A than wild type
      (WT) tobacco when grown under field conditions at elevated [CO(2)] (585 ppm)
      under fully open air fumigation. Growth under elevated [CO(2)] stimulated
      instantaneous A and the diurnal photosynthetic integral (A') more in
      transformants than WT. There was evidence of photosynthetic acclimation to
      elevated [CO(2)] via downregulation of V(c,max) in both WT and transformants.
      Nevertheless, greater carbon assimilation and electron transport rates (J and
      J(max)) for transformants led to greater yield increases than WT at elevated
      [CO(2)] compared to ambient grown plants. CONCLUSION: These results provide proof
      of concept that increasing content and activity of a single photosynthesis enzyme
      can enhance carbon assimilation and yield of C(3) crops grown at [CO(2)] expected
      by the middle of the 21st century.

PMID- 21884587
TI  - Quantitative utilization of prior biological knowledge in the Bayesian network
      modeling of gene expression data.
AB  - BACKGROUND: Bayesian Network (BN) is a powerful approach to reconstructing
      genetic regulatory networks from gene expression data. However, expression data
      by itself suffers from high noise and lack of power. Incorporating prior
      biological knowledge can improve the performance. As each type of prior knowledge
      on its own may be incomplete or limited by quality issues, integrating multiple
      sources of prior knowledge to utilize their consensus is desirable. RESULTS: We
      introduce a new method to incorporate the quantitative information from multiple
      sources of prior knowledge. It first uses the Naive Bayesian classifier to assess
      the likelihood of functional linkage between gene pairs based on prior knowledge.
      In this study we included cocitation in PubMed and schematic similarity in Gene
      Ontology annotation. A candidate network edge reservoir is then created in which
      the copy number of each edge is proportional to the estimated likelihood of
      linkage between the two corresponding genes. In network simulation the Markov
      Chain Monte Carlo sampling algorithm is adopted, and samples from this reservoir
      at each iteration to generate new candidate networks. We evaluated the new
      algorithm using both simulated and real gene expression data including that from
      a yeast cell cycle and a mouse pancreas development/growth study. Incorporating
      prior knowledge led to a ~2 fold increase in the number of known transcription
      regulations recovered, without significant change in false positive rate. In
      contrast, without the prior knowledge BN modeling is not always better than a
      random selection, demonstrating the necessity in network modeling to supplement
      the gene expression data with additional information. CONCLUSION: our new
      development provides a statistical means to utilize the quantitative information
      in prior biological knowledge in the BN modeling of gene expression data, which
      significantly improves the performance.

PMID- 21884588
TI  - Effects of a single intraperitoneal administration of cadmium on femoral bone
      structure in male rats.
AB  - BACKGROUND: Exposure to cadmium (Cd) is considered a risk factor for various bone
      diseases in humans and experimental animals. This study investigated the acute
      effects of Cd on femoral bone structure of adult male rats after a single
      intraperitoneal administration. METHODS: Ten 4-month-old male Wistar rats were
      injected intraperitoneally with a single dose of 2 mg CdCl2/kg body weight and
      killed 36 h after the Cd had been injected. Ten 4-month-old males served as a
      control group. Differences in body weight, femoral weight, femoral length and
      histological structure of the femur were evaluated between the two groups of
      rats. The unpaired Student's t-test was used for establishment of statistical
      significance. RESULTS: A single intraperitoneal administration of Cd had no
      significant effect on the body weight, femoral weight or femoral length. On the
      other hand, histological changes were significant. Rats exposed to Cd had
      significantly higher values of area, perimeter, maximum and minimum diameters of
      the primary osteons' vascular canals and Haversian canals. In contrast, a
      significant decrease in all variables of the secondary osteons was observed in
      these rats. CONCLUSIONS: The results indicate that, as expected, a single
      intraperitoneal administration of 2 mg CdCl2/kg body weight had no impact on
      macroscopic structure of rat's femora; however, it affected the size of vascular
      canals of primary osteons, Haversian canals, and secondary osteons.

PMID- 21884589
TI  - The association between systemic glucocorticoid therapy and the risk of infection
      in patients with rheumatoid arthritis: systematic review and meta-analyses.
AB  - INTRODUCTION: Infection is a major cause of morbidity and mortality in patients
      with rheumatoid arthritis (RA). The objective of this study was to perform a
      systematic review and meta-analysis of the effect of glucocorticoid (GC) therapy
      on the risk of infection in patients with RA. METHODS: A systematic review was
      conducted by using MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of
      Controlled Trials database to January 2010 to identify studies among populations
      of patients with RA that reported a comparison of infection incidence between
      patients treated with GC therapy and patients not exposed to GC therapy. RESULTS:
      In total, 21 randomised controlled trials (RCTs) and 42 observational studies
      were included. In the RCTs, GC therapy was not associated with a risk of
      infection (relative risk (RR), 0.97 (95% CI, 0.69, 1.36)). Small numbers of
      events in the RCTs meant that a clinically important increased or decreased risk
      could not be ruled out. The observational studies generated a RR of 1.67 (1.49,
      1.87), although significant heterogeneity was present. The increased risk (and
      heterogeneity) persisted when analyses were stratified by varying definitions of
      exposure, outcome, and adjustment for confounders. A positive dose-response
      effect was seen. CONCLUSIONS: Whereas observational studies suggested an
      increased risk of infection with GC therapy, RCTs suggested no increased risk.
      Inconsistent reporting of safety outcomes in the RCTs, as well as marked
      heterogeneity, probable residual confounding, and publication bias in the
      observational studies, limits the opportunity for a definitive conclusion.
      Clinicians should remain vigilant for infection in patients with RA treated with
      GC therapy.

PMID- 21884590
TI  - Cord blood calcium, phosphate, magnesium, and alkaline phosphatase gestational
      age-specific reference intervals for preterm infants.
AB  - BACKGROUND: The objective was to determine the influence of gestational age,
      maternal, and neonatal variables on reference intervals for cord blood bone
      minerals (calcium, phosphate, magnesium) and related laboratory tests (alkaline
      phosphatase, and albumin-adjusted calcium), and to develop gestational age
      specific reference intervals based on infants without influential pathological
      conditions. METHODS: Cross-sectional study. 702 babies were identified as
      candidates for this study in a regional referral neonatal unit. After exclusions
      (for anomalies, asphyxia, maternal magnesium sulfate administration, and death),
      relationships were examined between cord blood serum laboratory analytes
      (calcium, phosphate, magnesium, alkaline phosphatase, and albumin-adjusted
      calcium) with gestation age and also with maternal and neonatal variables using
      multiple linear regression. Infants with influential pathological conditions were
      omitted from the development of gestational age specific reference intervals for
      the following categories: 23-27, 28-31, 32-34, 35-36 and > 36 weeks. RESULTS:
      Among the 506 preterm and 54 terms infants included in the sample. Phosphate,
      magnesium, and alkaline phosphatase in cord blood serum decreased with
      gestational age, calcium increased with gestational age. Those who were triplets,
      small for gestational age, and those whose mother had pregnancy-induced
      hypertension were influential for most of the analytes. The reference ranges for
      the preterm infants >= 36 weeks were: phosphate 1.5 to 2.6 mmol/L (4.5 to 8.0
      mg/dL), calcium: 2.1 to 3.1 mmol/L (8.3 to 12.4 mg/dL); albumin-adjusted calcium:
      2.3 to 3.2 mmol/L (9.1 to 12.9 mg/dL); magnesium 0.6 to 1.0 mmol/L (1.4 to 2.3
      mg/dL), and alkaline phosphatase 60 to 301 units/L. CONCLUSIONS: These data
      suggest that gestational age, as well as potentially pathogenic maternal and
      neonatal variables should be considered in the development of reference intervals
      for preterm infants.

PMID- 21884591
TI  - Disjunctive shared information between ontology concepts: application to Gene
      Ontology.
AB  - BACKGROUND: The large-scale effort in developing, maintaining and making
      biomedical ontologies available motivates the application of similarity measures
      to compare ontology concepts or, by extension, the entities described therein. A
      common approach, known as semantic similarity, compares ontology concepts through
      the information content they share in the ontology. However, different
      disjunctive ancestors in the ontology are frequently neglected, or not properly
      explored, by semantic similarity measures. RESULTS: This paper proposes a novel
      method, dubbed DiShIn, that effectively exploits the multiple inheritance
      relationships present in many biomedical ontologies. DiShIn calculates the shared
      information content of two ontology concepts, based on the information content of
      the disjunctive common ancestors of the concepts being compared. DiShIn
      identifies these disjunctive ancestors through the number of distinct paths from
      the concepts to their common ancestors. CONCLUSIONS: DiShIn was applied to Gene
      Ontology and its performance was evaluated against state-of-the-art measures
      using CESSM, a publicly available evaluation platform of protein similarity
      measures. By modifying the way traditional semantic similarity measures calculate
      the shared information content, DiShIn was able to obtain a statistically
      significant higher correlation between semantic and sequence similarity.
      Moreover, the incorporation of DiShIn in existing applications that exploit
      multiple inheritance would reduce their execution time.

PMID- 21884592
TI  - CD23(+)/CD21(hi) B-cell translocation and ipsilateral lymph node collapse is
      associated with asymmetric arthritic flare in TNF-Tg mice.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune disease with
      episodic flares in affected joints. However, how arthritic flare occurs only in
      select joints during a systemic autoimmune disease remains an enigma. To better
      understand these observations, we developed longitudinal imaging outcomes of
      synovitis and lymphatic flow in mouse models of RA, and identified that
      asymmetric knee flare is associated with ipsilateral popliteal lymph node (PLN)
      collapse and the translocation of CD23(+)/CD21(hi) B-cells (B-in) into the
      paracortical sinus space of the node. In order to understand the relationship
      between this B-in translocation and lymph drainage from flaring joints, we tested
      the hypothesis that asymmetric tumor necrosis factor (TNF)-induced knee arthritis
      is associated with ipsilateral PLN and iliac lymph node (ILN) collapse, B-in
      translocation, and decreased afferent lymphatic flow. METHODS: TNF transgenic
      (Tg) mice with asymmetric knee arthritis were identified by contrast-enhanced
      (CE) magnetic resonance imaging (MRI), and PLN were phenotyped as "expanding" or
      "collapsed" using LNcap threshold = 30 (Arbitrary Unit (AU)). Inflammatory
      erosive arthritis was confirmed by histology. Afferent lymphatic flow to PLN and
      ILN was quantified by near infrared imaging of injected indocyanine green (NIR
      ICG). The B-in population in PLN and ILN was assessed by immunohistochemistry
      (IHC) and flow cytometry. Linear regression analyses of ipsilateral knee synovial
      volume and afferent lymphatic flow to PLN and ILN were performed. RESULTS:
      Afferent lymph flow to collapsed nodes was significantly lower (P < 0.05) than
      flow to expanding nodes by NIR-ICG imaging, and this occurred ipsilaterally.
      While both collapsed and expanding PLN and ILN had a significant increase (P <
      0.05) of B-in compared to wild type (WT) and pre-arthritic TNF-Tg nodes, B-in of
      expanding lymph nodes (LN) resided in follicular areas while B-in of collapsed LN
      were present within LYVE-1+ lymphatic vessels. A significant correlation (P <
      0.002) was noted in afferent lymphatic flow between ipsilateral PLN and ILN
      during knee synovitis. CONCLUSIONS: Asymmetric knee arthritis in TNF-Tg mice
      occurs simultaneously with ipsilateral PLN and ILN collapse. This is likely due
      to translocation of the expanded B-in population to the lumen of the lymphatic
      vessels, resulting in a dramatic decrease in afferent lymphatic flow. PLN
      collapse phenotype can serve as a new biomarker of knee flare.

PMID- 21884593
TI  - Characterization of a caleosin expressed during olive (Olea europaea L.) pollen
      ontogeny.
AB  - BACKGROUND: The olive tree is an oil-storing species, with pollen being the
      second most active site in storage lipid biosynthesis. Caleosins are proteins
      involved in storage lipid mobilization during seed germination. Despite the
      existence of different lipidic structures in the anther, there are no data
      regarding the presence of caleosins in this organ to date. The purpose of the
      present work was to characterize a caleosin expressed in the olive anther over
      different key stages of pollen ontogeny, as a first approach to unravel its
      biological function in reproduction. RESULTS: A 30 kDa caleosin was identified in
      the anther tissues by Western blot analysis. Using fluorescence and transmission
      electron microscopic immunolocalization methods, the protein was first localized
      in the tapetal cells at the free microspore stage. Caleosins were released to the
      anther locule and further deposited onto the sculptures of the pollen exine. As
      anthers developed, tapetal cells showed the presence of structures constituted by
      caleosin-containing lipid droplets closely packed and enclosed by ER-derived
      cisternae and vesicles. After tapetal cells lost their integrity, the caleosin
      containing remnants of the tapetum filled the cavities of the mature pollen
      exine, forming the pollen coat. In developing microspores, this caleosin was
      initially detected on the exine sculptures. During pollen maturation, caleosin
      levels progressively increased in the vegetative cell, concurrently with the
      number of oil bodies. The olive pollen caleosin was able to bind calcium in
      vitro. Moreover, PEGylation experiments supported the structural conformation
      model suggested for caleosins from seed oil bodies. CONCLUSIONS: In the olive
      anther, a caleosin is expressed in both the tapetal and germ line cells, with its
      synthesis independently regulated. The pollen oil body-associated caleosin is
      synthesized by the vegetative cell, whereas the protein located on the pollen
      exine and its coating has a sporophytic origin. The biological significance of
      the caleosin in the reproductive process in species possessing lipid-storing
      pollen might depend on its subcellular emplacement. The pollen inner caleosin may
      be involved in OB biogenesis during pollen maturation. The protein located on the
      outside might rather play a function in pollen-stigma interaction during pollen
      hydration and germination.

PMID- 21884595
TI  - Impaired spatial and contextual memory formation in galectin-1 deficient mice.
AB  - Galectins are a 15 member family of carbohydrate-binding proteins that have been
      implicated in cancer, immunity, inflammation and development. While galectins are
      expressed in the central nervous system, little is known about their function in
      the adult brain. Previously we have shown that galectin-1 (gal-1) is expressed in
      the adult hippocampus, and, in particular, in putative neural stem cells in the
      subgranular zone. To evaluate how gal-1 might contribute to hippocampal memory
      function here we studied galectin-1 null mutant (gal-1-/-) mice. Compared to
      their wildtype littermate controls, gal-1-/- mice exhibited impaired spatial
      learning in the water maze and contextual fear learning. Interestingly, tone fear
      conditioning was normal in gal-1-/- mice suggesting that loss of gal-1 might
      especially impact hippocampal learning and memory. Furthermore, gal-1-/- mice
      exhibited normal motor function, emotion and sensory processing in a battery of
      other behavioral tests, suggesting that non-mnemonic performance deficits are
      unlikely to account for the spatial and contextual learning deficits. Together,
      these data reveal a role for galectin-carbohydrate signalling in hippocampal
      memory function.

PMID- 21884596
TI  - Solid-state dye-sensitized solar cells based on ZnO nanoparticle and nanorod
      array hybrid photoanodes.
AB  - The effect of ZnO photoanode morphology on the performance of solid-state dye
      sensitized solar cells (DSSCs) is reported. Four different structures of dye
      loaded ZnO layers have been fabricated in conjunction with poly(3
      hexylthiophene). A significant improvement in device efficiency with ZnO nanorod
      arrays as photoanodes has been achieved by filling the interstitial voids of the
      nanorod arrays with ZnO nanoparticles. The overall power conversion efficiency
      increases from 0.13% for a nanorod-only device to 0.34% for a device with
      combined nanoparticles and nanorod arrays. The higher device efficiency in solid
      state DSSCs with hybrid nanorod/nanoparticle photoanodes is originated from both
      large surface area provided by nanoparticles for dye adsorption and efficient
      charge transport provided by the nanorod arrays to reduce the recombinations of
      photogenerated carriers.

PMID- 21884594
TI  - Retrotransposon-centered analysis of piRNA targeting shows a shift from active to
      passive retrotransposon transcription in developing mouse testes.
AB  - BACKGROUND: Piwi-associated RNAs (piRNAs) bind transcripts from retrotransposable
      elements (RTE) in mouse germline cells and seemingly act as guides for genomic
      methylation, thereby repressing the activity of RTEs. It is currently unknown if
      and how Piwi proteins distinguish RTE transcripts from other cellular RNAs.
      During germline development, the main target of piRNAs switch between different
      types of RTEs. Using the piRNA targeting of RTEs as an indicator of RTE activity,
      and considering the entire population of genomic RTE loci along with their age
      and location, this study aims at further elucidating the dynamics of RTE activity
      during mouse germline development. RESULTS: Due to the inherent sequence
      redundancy between RTE loci, assigning piRNA targeting to specific loci is
      problematic. This limits the analysis, although certain features of piRNA
      targeting of RTE loci are apparent. As expected, young RTEs display a much higher
      level of piRNA targeting than old RTEs. Further, irrespective of age, RTE loci
      near protein-coding coding genes are targeted to a greater extent than RTE loci
      far from genes. During development, a shift in piRNA targeting is observed, with
      a clear increase in the relative piRNA targeting of RTEs residing within
      boundaries of protein-coding gene transcripts. CONCLUSIONS: Reanalyzing published
      piRNA sequences and taking into account the features of individual RTE loci
      provide novel insight into the activity of RTEs during development. The obtained
      results are consistent with some degree of proportionality between what
      transcripts become substrates for Piwi protein complexes and the level by which
      the transcripts are present in the cell. A transition from active transcription
      of RTEs to passive co-transcription of RTE sequences residing within protein
      coding transcripts appears to take place in postnatal development. Hence, the
      previously reported increase in piRNA targeting of SINEs in postnatal testis
      development does not necessitate widespread active transcription of SINEs, but
      may simply be explained by the prevalence of SINEs residing in introns.

PMID- 21884597
TI  - Factors that influence the response of the LysR type transcriptional regulators
      to aromatic compounds.
AB  - BACKGROUND: The transcriptional regulators DntR, NagR and NtdR have a high
      sequence identity and belong to the large family of LysR type transcriptional
      regulators (LTTRs). These three regulators are all involved in regulation of
      genes identified in pathways for degradation of aromatic compounds. They activate
      the transcription of these genes in the presence of an inducer, but the inducer
      specificity profiles are different. RESULTS: The results from this study show
      that NtdR has the broadest inducer specificity, responding to several nitro
      aromatic compounds. Mutational studies of residues that differ between DntR, NagR
      and NtdR suggest that a number of specific residues are involved in the broader
      inducer specificity of NtdR when compared to DntR and NagR. The inducer response
      was also investigated as a function of the experimental conditions and a number
      of parameters such as the growth media, plasmid arrangement of the LTTR-encoding
      genes, promoter and gfp reporter gene, and the presence of a His6-tag were shown
      to affect the inducer response in E.coli DH5alpha. Furthermore, the response upon
      addition of both salicylate and 4-nitrobenzoate to the growth media was larger
      than the sum of responses upon addition of each of the compounds, which suggests
      the presence of a secondary binding site, as previously reported for other LTTRs.
      CONCLUSIONS: Optimization of the growth conditions and gene arrangement resulted
      in improved responses to nitro-aromatic inducers. The data also suggests the
      presence of a previously unknown secondary binding site in DntR, analogous to
      that of BenM.

PMID- 21884598
TI  - Use of an amplatzer vascular plug in embolization of a pulmonary artery aneurysm
      in a case of hughes-stovin syndrome: a case report.
AB  - INTRODUCTION: Hughes-Stovin syndrome is a rare condition characterized by
      peripheral deep venous thrombosis accompanied by single or multiple pulmonary
      arterial aneurysms. The limited number of cases has precluded controlled studies
      of the management of pulmonary artery aneurysms, which usually cause massive
      hemoptysis leading to death. This is the first report of a new endovascular
      treatment of a single large pulmonary arterial aneurysm. CASE PRESENTATION: An 18
      year-old Caucasian man was referred to our department with recurrent severe
      hemoptysis. His medical history included Hughes-Stovin syndrome diagnosed during
      a recent hospital admission. The patient was initially treated with
      corticosteroids. Because of his recurrent hemoptysis, we decided to embolize a
      3.5 cm pulmonary arterial aneurysm using an Amplatzer Vascular Plug. The
      procedure was not complicated, and the patient's post-intervention course was
      uneventful. The patient has remained free from any complications of the
      embolization 36 months after the procedure. CONCLUSION: Percutaneous embolization
      of a single large pulmonary artery aneurysm with an Amplatzer Vascular Plug in a
      patient with Hughes-Stovin syndrome is a less invasive procedure that represents
      the best multidisciplinary approach in treating these patients.

PMID- 21884599
TI  - Frequency of human immunodeficiency virus (HIV) testing in urban vs. rural areas
      of the United States: results from a nationally-representative sample.
AB  - BACKGROUND: Studies in the United States show that rural persons with HIV are
      more likely than their urban counterparts to be diagnosed at a late stage of
      infection, suggesting missed opportunities for HIV testing in rural areas. To
      inform discussion of HIV testing policies in rural areas, we generated nationally
      representative, population-based estimates of HIV testing frequencies in urban
      vs. rural areas of the United States. METHODS: Secondary analysis of 2005 and
      2009 Behavioral Risk Factor Surveillance System (BRFSS) data. Dependent variables
      were self-reported lifetime and past-year HIV testing. Urban vs. rural residence
      was determined using the metropolitan area framework and Urban Influence Codes
      and was categorized as 1) metropolitan, center city (the most urban); 2)
      metropolitan, other; 3) non-metropolitan, adjacent to metropolitan; 4) non
      metropolitan, micropolitan; and 4) remote, non-metropolitan (the most rural).
      RESULTS: The 2005 sample included 257,895 respondents. Lifetime HIV testing
      frequencies ranged from 43.6% among persons residing in the most urban areas to
      32.2% among persons in the most rural areas (P < 0.001). Past-year testing
      frequencies ranged from 13.5% to 7.3% in these groups (P < 0.001). After
      adjusting for demographics (age, sex, race/ethnicity, and region of residence)
      and self-reported HIV risk factors, persons in the most remote rural areas were
      substantially less likely than persons in the most urban areas to report HIV
      testing in the past year (odds ratio 0.65, 95% CI 0.57-0.75). Testing rates in
      urban and rural areas did not change substantively following the 2006 Centers for
      Disease Control and Prevention recommendation for routine, population-based HIV
      testing in healthcare settings. In metropolitan (urban) areas, 11.5% (95% CI 11.2
      11.8) reported past-year HIV testing in 2005 vs. 11.4% (95% CI 11.1%-11.7%) in
      2009 (P = 0.93). In non-metropolitan areas, 8.7% (95% CI 8.2%-9.2%) were tested
      in 2005 vs. 7.7% (95% CI 7.2%-8.2%) in 2009 (P = 0.03). CONCLUSIONS: Rural
      persons are less likely than urban to report prior HIV testing, which may
      contribute to later HIV diagnosis in rural areas. There is need to consider
      strategies to increase HIV testing in rural areas.

PMID- 21884600
TI  - Successful one stage operation for a synchronous, duodenal carcinoma, colonic
      carcinoma and renal oncocytoma in an adult patient.
AB  - We report a rare case of synchronous duodenal carcinoma, colonic carcinoma and
      renal oncocytoma successfully treated using a one-stage surgical approach.
      Potential risk factors for multiple primary malignancies associated with duodenal
      carcinoma are discussed. This case illustrates several practice points for
      consideration: 1. Patients presenting with small intestinal carcinomas have a
      higher than average chance of developing second primary tumors in other organs;
      this should be taken into consideration during staging and follow-up. 2. For full
      staging of patients presenting with small bowel tumors, upper and lower
      gastrointestinal endoscopy and PET scanning should be considered. 3. A one-stage
      surgical procedure can be used safely and successfully for multiple synchronous
      primary tumors.

PMID- 21884601
TI  - Integrated safety in tocilizumab clinical trials.
AB  - INTRODUCTION: The efficacy and safety of tocilizumab in patients with rheumatoid
      arthritis have been evaluated in a comprehensive phase 3 program. Patients from
      these randomized trials could receive tocilizumab treatment in open-label
      extension trials. Here, the long-term safety profile of tocilizumab, using pooled
      data from all of these trials, is reported. METHODS: Cumulative safety data (as
      of February 6, 2009) from five core phase 3 trials, two ongoing extension trials,
      and one clinical pharmacology study were analyzed. Two patient populations were
      evaluated: an all-control population (n = 4,199), which included all patients
      randomly assigned in the placebo-controlled portions of the five core studies,
      and an all-exposed population (n = 4,009), which included patients from any of
      the eight studies who received at least one dose of tocilizumab. RESULTS: Total
      exposure to tocilizumab was 8,580 patient years (PY), and total duration of
      observation was 9,414 PY. Overall adverse event (AE) and serious AE (SAE) rates
      were 278.2/100 PY and 14.4/100 PY, respectively. These events included serious
      infections (4.7/100 PY), opportunistic infections (0.23/100 PY), gastrointestinal
      perforations (0.28/100 PY), malignancy (1.1/100 PY), myocardial infarction
      (0.25/100 PY), and stroke (0.19/100 PY). The rates of SAEs and serious infections
      were stable over time; no increase with prolonged exposure was noted.
      CONCLUSIONS: The longer-term safety profile of tocilizumab (mean treatment
      duration, 2.4 years) is consistent with that observed in the phase 3 studies
      (duration up to 1 year).

PMID- 21884602
TI  - Combination of hydrogel nanoparticles and proteomics to reveal secreted proteins
      associated with decidualization of human uterine stromal cells.
AB  - BACKGROUND: Identification of secreted proteins of low abundance is often limited
      by abundant and high molecular weight (MW) proteins. We have optimised a
      procedure to overcome this limitation. RESULTS: Low MW proteins in the
      conditioned media of cultured cells were first captured using dual-size
      exclusion/affinity hydrogel nanoparticles and their identities were then revealed
      by proteomics. CONCLUSIONS: This technique enables the analysis of secreted
      proteins of cultured cells low MW and low abundance.

PMID- 21884604
TI  - Intensive medical student involvement in short-term surgical trips provides safe
      and effective patient care: a case review.
AB  - BACKGROUND: The hierarchical nature of medical education has been thought
      necessary for the safe care of patients. In this setting, medical students in
      particular have limited opportunities for experiential learning. We report on a
      student-faculty collaboration that has successfully operated an annual, short
      term surgical intervention in Haiti for the last three years. Medical students
      were responsible for logistics and were overseen by faculty members for patient
      care. Substantial planning with local partners ensured that trip activities
      supplemented existing surgical services. A case review was performed
      hypothesizing that such trips could provide effective surgical care while also
      providing a suitable educational experience. FINDINGS: Over three week-long
      trips, 64 cases were performed without any reported complications, and no
      immediate perioperative morbidity or mortality. A plurality of cases were complex
      urological procedures that required surgical skills that were locally unavailable
      (43%). Surgical productivity was twice that of comparable peer institutions in
      the region. Student roles in patient care were greatly expanded in comparison to
      those at U.S. academic medical centers and appropriate supervision was
      maintained. DISCUSSION: This demonstration project suggests that a properly
      designed surgical trip model can effectively balance the surgical needs of the
      community with an opportunity to expose young trainees to a clinical and cross
      cultural experience rarely provided at this early stage of medical education. Few
      formalized programs currently exist although the experience above suggests the
      rewarding potential for broad-based adoption.

PMID- 21884603
TI  - The Sydney playground project: popping the bubblewrap--unleashing the power of
      play: a cluster randomized controlled trial of a primary school playground-based
      intervention aiming to increase children's physical activity and social skills.
AB  - BACKGROUND: In the Westernised world, numerous children are overweight and have
      problems with bullying and mental health. One of the underlying causes for all
      three is postulated to be a decrease in outdoor free play. The aim of the Sydney
      Playground Project is to demonstrate the effectiveness of two simple
      interventions aimed to increase children's physical activity and social skills.
      METHODS/DESIGN: This study protocol describes the design of a 3-year cluster
      randomised controlled trial (CRCT), in which schools are the clusters. The study
      consists of a 13-week intervention and 1 week each of pre-and post-testing. We
      are recruiting 12 schools (6 control; 6 intervention), with 18 randomly chosen
      participants aged 5 to 7 years in each school. The two intervention strategies
      are: (1) Child-based intervention: Unstructured materials with no obvious play
      value introduced to the playground; and (2) Adult-based intervention: Risk
      reframing sessions held with parents and teachers with the aim of exploring the
      benefits of allowing children to engage in activities with uncertain outcomes.
      The primary outcome of the study, physical activity as measured by accelerometer
      counts, is assessed at baseline and post-intervention. Additional assessments
      include social skills and interactions, self-concept, after school time use and
      anthropometric data. Qualitative data (i.e., transcriptions of audio recordings
      from the risk reframing sessions and of interviews with selected teacher and
      parent volunteers) are analysed to understand their perceptions of risk in play.
      The control schools have recess as usual. In addition to outcome evaluation,
      regular process evaluation sessions are held to monitor fidelity to the
      treatment. DISCUSSION: These simple interventions, which could be adopted in
      every primary school, have the potential of initiating a self-sustaining cycle of
      prevention for childhood obesity, bullying and mental ill health. TRIAL
      REGISTRATION: Australian and New Zealand Clinical Trials Registration Number
      ACTRN12611000089932.

PMID- 21884605
TI  - Q&A: The Alzheimer's Disease Neuroimaging Initiative.

PMID- 21884606
TI  - The impact of different doses of vitamin A supplementation on male and female
      mortality. A randomised trial from Guinea-Bissau.
AB  - BACKGROUND: Vitamin A supplementation (VAS) given to children between 6 months
      and 5 years of age is known to reduce mortality in low-income countries. We have
      previously observed that girls benefit more from a lower dose of VAS than the one
      recommended by WHO, the effect being strongest if diphtheria-tetanus-pertussis
      vaccine (DTP) was the most recent vaccination. We aimed to test these
      observations. METHODS: During national immunisations days in Guinea-Bissau, West
      Africa, combining oral polio vaccination and VAS, we randomised 8626 children
      between 6 months and 5 years of age to receive the dose of VAS recommended by WHO
      or half this dose. Mortality rate ratios (MRRs) were assessed after 6 and 12
      month. RESULTS: The overall mortality rate among participants was lower than
      expected. There was no significant difference in mortality at 6 months and 12
      months of follow up between the low dose VAS group and the recommended dose VAS
      group. The MRRs were 1.23 (0.60-2.54) after 6 months and 1.17 (0.73-1.87) after
      12 months. This tendency was similar in boys and girls. The low dose was not
      associated with lower mortality in girls if the most recent vaccine was DTP (MRR
      = 0.60 (0.14-2.50) after 6 months). CONCLUSION: Our sample size does not permit
      firm conclusions since mortality was lower than expected. We could not confirm a
      beneficial effect of a lower dose of VAS on mortality in girls. TRIAL
      REGISTRATION: The study was registered under clinicaltrials.gov, number
      NCT00168636.

PMID- 21884607
TI  - Traditional-medical knowledge and perception of pangolins (Manis sps) among the
      Awori people, Southwestern Nigeria.
AB  - medicines is taken from the wild; hence demand by traditional medicine is a cause
      of over-exploitation of wild animals. Indiscriminate use of endangered species
      portends grievous implications for biodiversity conservation. This study
      investigated the dynamics of the use of pangolin in trado-medicinal preparations
      amongst the Awori people. METHODS: Forty traditional Yorubic-medical
      practitioners (tymps) selected through stratified random-sampling technique were
      interviewed using open-ended questionnaires. Various aspects of the utilisation
      of pangolin in traditional medicinal practices were investigated. Data collected
      were analysed using simple frequencies and percentages. RESULTS: An average of
      1.6 pangolins were utilised per tymp per month. About 43% of respondents
      contracted hunters for deliberate searches for the animals. More than 92%
      believed that pangolins' abundance is steadily decreasing. Above 97% reported a
      continuous decline in the size of pangolin. Pangolin was used in treating 47
      conditions. Situations accommodated included those that can be treated by
      orthodox medicine like rheumatism and venereal diseases as well as some that are
      out of range for orthodox medicine including kleptomania and good luck charms.
      Some substitute animals like gorilla are under a greater conservation threat than
      pangolin. CONCLUSIONS: Utilisation of pangolin in traditional medicine has no
      consideration for sustainability. Awareness should be created on people as
      regards the implications of unsustainable depletion of medicinal resources.
      Efforts should be intensified on ex-situ breeding of pangolin while subjecting
      the scales and other parts to laboratory studies to determine the bioactive
      constituents.

PMID- 21884608
TI  - Interactions between HIV infection and chronic obstructive pulmonary disease:
      Clinical and epidemiological aspects.
AB  - INTRODUCTION: An association between HIV infection and chronic obstructive
      pulmonary disease (COPD) has been observed in several studies. OBJECTIVE AND
      METHODS: we conducted a review of the literature linking HIV infection to COPD,
      focusing on clinical and epidemiological data published before and during
      widespread highly active antiretroviral therapy (HAART). RESULTS: Interactions
      between HIV infection and COPD appear to be influenced by multiple factors. In
      particular, the bronchopulmonary tract can be damaged by HIV infection, the
      immunodeficiency it induces, and the resulting increase in the risk of pulmonary
      infections. In addition, the prevalence of smoking and intravenous drug use is
      higher in HIV-infected populations, also increasing the risk of COPD. Before the
      advent of HAART, respiratory tract infections probably played a major role. Since
      the late 1990s and the widespread use of HAART, the frequency of opportunistic
      infections has fallen but new complications have emerged as life expectancy has
      increased. CONCLUSION: given the high prevalence of smoking among HIV-infected
      patients, COPD may contribute significantly to morbidity and mortality in this
      setting.

PMID- 21884609
TI  - Self-assessment of intercultural communication skills: a survey of physicians and
      medical students in Geneva, Switzerland.
AB  - BACKGROUND: Physicians working with multicultural populations need to know how to
      elicit the patient's understanding of the illness; determine the patient's
      sociocultural context and identify any issues that might affect care; communicate
      effectively across patient-provider social and cultural differences; and
      collaborate effectively with an interpreter. Skills self-assessment can
      contribute to identifying training needs and monitoring skills development in
      these areas. METHODS: As part of a larger study exploring the knowledge,
      attitudes and practices of Geneva physicians and medical students regarding the
      care of immigrant patients, we asked respondents to self-rate their ability to
      perform a range of common yet challenging intercultural communication tasks.
      RESULTS: Overall, respondents rated themselves less competent at intercultural
      tasks than at basic medical skills and less competent at specific intercultural
      communication skills than at general intercultural skills. Qualified doctors (as
      opposed to students), those with greater interest in caring for immigrants, and
      those who rarely encountered difficulties with immigrants rated themselves
      significantly more competent for all clinical tasks. Having a higher percentage
      of immigrant patients and previous cultural competence training predicted greater
      self-rated intercultural communication skills. CONCLUSION: Our self-assessment
      results suggest that students and physicians should be provided with the
      opportunity to practice intercultural skills with immigrant patients as part of
      their cultural competence training. To strengthen the validity of self-assessment
      measures, they should ideally be combined with more objective methods to assess
      actual skills.

PMID- 21884611
TI  - GO-based functional dissimilarity of gene sets.
AB  - BACKGROUND: The Gene Ontology (GO) provides a controlled vocabulary for
      describing the functions of genes and can be used to evaluate the functional
      coherence of gene sets. Many functional coherence measures consider each pair of
      gene functions in a set and produce an output based on all pairwise distances. A
      single gene can encode multiple proteins that may differ in function. For each
      functionality, other proteins that exhibit the same activity may also
      participate. Therefore, an identification of the most common function for all of
      the genes involved in a biological process is important in evaluating the
      functional similarity of groups of genes and a quantification of functional
      coherence can helps to clarify the role of a group of genes working together.
      RESULTS: To implement this approach to functional assessment, we present GFD (GO
      based Functional Dissimilarity), a novel dissimilarity measure for evaluating
      groups of genes based on the most relevant functions of the whole set. The
      measure assigns a numerical value to the gene set for each of the three GO sub
      ontologies. CONCLUSIONS: Results show that GFD performs robustly when applied to
      gene set of known functionality (extracted from KEGG). It performs particularly
      well on randomly generated gene sets. An ROC analysis reveals that the
      performance of GFD in evaluating the functional dissimilarity of gene sets is
      very satisfactory. A comparative analysis against other functional measures, such
      as GS2 and those presented by Resnik and Wang, also demonstrates the robustness
      of GFD.

PMID- 21884610
TI  - Changes in Holstein cow milk and serum proteins during intramammary infection
      with three different strains of Staphylococcus aureus.
AB  - BACKGROUND: Staphylococcus aureus is one of the most prevalent pathogens to cause
      mastitis in dairy cattle. Intramammary infection of dairy cows with S. aureus is
      often subclinical, due to the pathogen's ability to evade the innate defense
      mechanisms, but this can lead to chronic infection. A sub-population of S.
      aureus, known as small colony variant (SCV), displays atypical phenotypic
      characteristics, causes persistent infections, and is more resistant to
      antibiotics than parent strains. Therefore, it was hypothesized that the host
      immune response will be different for SCV than its parental or typical strains of
      S. aureus. In this study, the local and systemic immune protein responses to
      intramammary infection with three strains of S. aureus, including a naturally
      occurring bovine SCV strain (SCV Heba3231), were characterized. Serum and casein
      depleted milk cytokine levels (interleukin-8, interferon-gamma, and transforming
      growth factor-beta1), as well as serum haptoglobin concentrations were monitored
      over time after intramammary infection with each of the three S. aureus strains.
      Furthermore, comparative proteomics was used to evaluate milk proteome profiles
      during acute and chronic phases of S. aureus intramammary infection. RESULTS:
      Serum IL-8, IFN-gamma, and TGF-beta1 responses differed in dairy cows challenged
      with different strains of S. aureus. Changes in overall serum haptoglobin
      concentrations were observed for each S. aureus challenge group, but there were
      no significant differences observed between groups. In casein-depleted milk,
      strain-specific differences in the host IFN-gamma response were observed, but
      inducible IL-8 and TGF-beta1 concentrations were not different between groups.
      Proteomic analysis of the milk following intramammary infection revealed unique
      host protein expression profiles that were dependent on the infecting strain as
      well as phase of infection. Notably, the protein, component-3 of the proteose
      peptone (CPP3), was differentially expressed between the S. aureus treatment
      groups, implicating it as a potential antimicrobial peptide involved in host
      defense against S. aureus intramammary infection. CONCLUSIONS: Intramammary
      infection of dairy cattle with S. aureus causes an up-regulation of serum and
      milk immune-related proteins, and these responses vary depending on the infecting
      strain.

PMID- 21884612
TI  - Metabolic and kinetic analyses of influenza production in perfusion HEK293 cell
      culture.
AB  - BACKGROUND: Cell culture-based production of influenza vaccine remains an
      attractive alternative to egg-based production. Short response time and high
      production yields are the key success factors for the broader adoption of cell
      culture technology for industrial manufacturing of pandemic and seasonal
      influenza vaccines. Recently, HEK293SF cells have been successfully used to
      produce influenza viruses, achieving hemagglutinin (HA) and infectious viral
      particle (IVP) titers in the highest ranges reported to date. In the same study,
      it was suggested that beyond 4 * 10(6) cells/mL, viral production was limited by
      a lack of nutrients or an accumulation of toxic products. RESULTS: To further
      improve viral titers at high cell densities, perfusion culture mode was
      evaluated. Productivities of both perfusion and batch culture modes were compared
      at an infection cell density of 6 * 10(6) cells/mL. The metabolism, including
      glycolysis, glutaminolysis and amino acids utilization as well as physiological
      indicators such as viability and apoptosis were extensively documented for the
      two modes of culture before and after viral infection to identify potential
      metabolic limitations. A 3 L bioreactor with a perfusion rate of 0.5 vol/day
      allowed us to reach maximal titers of 3.3 * 10(11) IVP/mL and 4.0 logHA units/mL,
      corresponding to a total production of 1.0 * 10(15) IVP and 7.8 logHA units after
      3 days post-infection. Overall, perfusion mode titers were higher by almost one
      order of magnitude over the batch culture mode of production. This improvement
      was associated with an activation of the cell metabolism as seen by a 1.5-fold
      and 4-fold higher consumption rates of glucose and glutamine respectively. A
      shift in the viral production kinetics was also observed leading to an
      accumulation of more viable cells with a higher specific production and causing
      an increase in the total volumetric production of infectious influenza particles.
      CONCLUSIONS: These results confirm that the HEK293SF cell is an excellent
      substrate for high yield production of influenza virus. Furthermore, there is
      great potential in further improving the production yields through better control
      of the cell culture environment and viral production kinetics. Once accomplished,
      this cell line can be promoted as an industrial platform for cost-effective
      manufacturing of the influenza seasonal vaccine as well as for periods of peak
      demand during pandemics.

PMID- 21884613
TI  - Spectrum of antihypertensive therapy in South Asians at a tertiary care hospital
      in Pakistan.
AB  - BACKGROUND: Despite available guidelines on hypertension (HTN), use of
      antihypertensives is variable. This study was designed to ascertain frequency of
      patients on monotherapy and > 1 antihypertensive therapy and also to ascertain
      proportion of patients on diuretic therapy. METHODS: It was a crossectional study
      conducted on 1191 adults(age > 18 yrs)hypertensive patients selected by
      computerized International Classification of Diseases -9-coordination and
      maintenance (ICD-9-CM) presenting to a tertiary care hospital in Pakistan. Data
      on demographics, comorbids, type of antihypertensive drug, number of
      antihypertensive drug and mean duration of antihypertensive drug was recorded
      over 1.5 year period (2008-09). Blood pressure was recorded on admission. Primary
      outcome was use of combination therapy and secondary outcome was use of diuretic
      therapy. RESULTS: A total of 1191 participants were included. Mean age(SD) was
      62.55(12.47) years, 45.3%(540) were males. Diabetes was the most common comorbid;
      46.3%(551). Approximately 85% of patients had controlled hypertension. On
      categorization of anti hypertensive use into 3 categories;41.2%(491) were on
      monotherapy,32.2%(384) were on 2 drug therapy,26.5%(316) were on >=3 drug
      therapy. Among those who were on monotherapy for HTN;34%(167) were on calcium
      channel blockers,30.10%(148) were on beta blockers, 22.80%(112) were on
      Angiotensin converting enzyme (ACE) inhibitors,12%(59) were on diuretics and
      2.20%(11) were on Angiotensin receptor blockers(ARB). Use of combination
      antihypertensive therapy was significantly high in patients with ischemic heart
      disease(IHD)(p < 0.001). Use of diuretics was in 31% (369) patients. Use of
      diuretics was significantly less in patients with comorbids of diabetes (p 0.02),
      Chronic kidney disease(CKD)(p 0.003), IHD (p 0.001) respectively CONCLUSION: Most
      patients presenting to our tertiary care center were on combination therapy.
      Calcium channel blocker is the most common anti hypertensive drug used as
      monotherapy and betablockers are used as the most common antihypertensive in
      combination. Only a third of patients were on diuretic as an antihypertensive
      therapy.

PMID- 21884614
TI  - Co-occurrence of diabetes, myocardial infarction, stroke, and cancer: quantifying
      age patterns in the Dutch population using health survey data.
AB  - BACKGROUND: The high prevalence of chronic diseases in Western countries implies
      that the presence of multiple chronic diseases within one person is common.
      Especially at older ages, when the likelihood of having a chronic disease
      increases, the co-occurrence of distinct diseases will be encountered more
      frequently. The aim of this study was to estimate the age-specific prevalence of
      multimorbidity in the general population. In particular, we investigate to what
      extent specific pairs of diseases cluster within people and how this deviates
      from what is to be expected under the assumption of the independent occurrence of
      diseases (i.e., sheer coincidence). METHODS: We used data from a Dutch health
      survey to estimate the prevalence of pairs of chronic diseases specified by age.
      Diseases we focused on were diabetes, myocardial infarction, stroke, and cancer.
      Multinomial P-splines were fitted to the data to model the relation between age
      and disease status (single versus two diseases). To assess to what extent co
      occurrence cannot be explained by independent occurrence, we estimated
      observed/expected co-occurrence ratios using predictions of the fitted regression
      models. RESULTS: Prevalence increased with age for all disease pairs. For all
      disease pairs, prevalence at most ages was much higher than is to be expected on
      the basis of coincidence. Observed/expected ratios of disease combinations
      decreased with age. CONCLUSION: Common chronic diseases co-occur in one
      individual more frequently than is due to chance. In monitoring the occurrence of
      diseases among the population at large, such multimorbidity is insufficiently
      taken into account.

PMID- 21884615
TI  - Characterization of the Rac guanine nucleotide exchange factor P-Rex1 in
      platelets.
AB  - BACKGROUND: Blood platelets undergo a carefully regulated change in shape to
      serve as the primary mediators of hemostasis and thrombosis. These processes
      manifest through platelet spreading and aggregation and are dependent on platelet
      actin cytoskeletal changes orchestrated by the Rho GTPase family member Rac1. To
      elucidate how Rac1 is regulated in platelets, we captured Rac1-interacting
      proteins from platelets and identified Rac1-associated proteins by mass
      spectrometry. FINDINGS: Here, we demonstrate that Rac1 captures the Rac guanine
      nucleotide exchange factor P-Rex1 from platelet lysates. Western blotting
      experiments confirmed that P-Rex1 is expressed in platelets and associated with
      Rac1. To investigate the functional role of platelet P-Rex1, platelets from P
      Rex1-/--deficient mice were treated with platelet agonists or exposed to platelet
      activating surfaces of fibrinogen, collagen and thrombin. Platelets from P-Rex1-/
      mice responded to platelet agonists and activating surfaces similarly to wild
      type platelets. CONCLUSIONS: These findings suggest that P-Rex1 is not required
      for Rac1-mediated platelet activation and that the GEF activities of P-Rex1 may
      be more specific to GPCR chemokine receptor mediated processes in immune cells
      and tumor cells.

PMID- 21884616
TI  - The counseling African Americans to Control Hypertension (CAATCH) Trial: baseline
      demographic, clinical, psychosocial, and behavioral characteristics.
AB  - BACKGROUND: Effectiveness of combined physician and patient-level interventions
      for blood pressure (BP) control in low-income, hypertensive African Americans
      with multiple co-morbid conditions remains largely untested in community-based
      primary care practices. Demographic, clinical, psychosocial, and behavioral
      characteristics of participants in the Counseling African American to Control
      Hypertension (CAATCH) Trial are described. CAATCH evaluates the effectiveness of
      a multi-level, multi-component, evidence-based intervention compared with usual
      care (UC) in improving BP control among poorly controlled hypertensive African
      Americans who receive primary care in Community Health Centers (CHCs). METHODS:
      Participants included 1,039 hypertensive African Americans receiving care in 30
      CHCs in the New York Metropolitan area. Baseline data on participant demographic,
      clinical (e.g., BP, anti-hypertensive medications), psychosocial (e.g.,
      depression, medication adherence, self-efficacy), and behavioral (e.g., exercise,
      diet) characteristics were gathered through direct observation, chart review, and
      interview. RESULTS: The sample was primarily female (71.6%), middle-aged (mean
      age = 56.9 +/- 12.1 years), high school educated (62.4%), low-income (72.4%
      reporting less than $20,000/year income), and received Medicaid (35.9%) or
      Medicare (12.6%). Mean systolic and diastolic BP were 150.7 +/- 16.7 mm Hg and
      91.0 +/- 10.6 mm Hg, respectively. Participants were prescribed an average of 2.5
      +/- 1.9 antihypertensive medications; 54.8% were on a diuretic; 33.8% were on a
      beta blocker; 41.9% were on calcium channel blockers; 64.8% were on angiotensin
      converting enzyme (ACE) inhibitors/angiotensin receptor blockers (ARBs). One
      quarter (25.6%) of the sample had resistant hypertension; one-half (55.7%)
      reported medication non-adherence. Most (79.7%) reported one or more co-morbid
      medical conditions. The majority of the patients had a Charlson Co-morbidity
      score >= 2. Diabetes mellitus was common (35.8%), and moderate/severe depression
      was present in 16% of participants. Participants were sedentary (835.3 +/-
      1,644.2 Kcal burned per week), obese (59.7%), and had poor global physical
      health, poor eating habits, high health literacy, and good overall mental health.
      CONCLUSIONS: A majority of patients in the CAATCH trial exhibited adverse
      lifestyle behaviors, and had significant medical and psychosocial barriers to
      adequate BP control. Trial outcomes will shed light on the effectiveness of
      evidence-based interventions for BP control when implemented in real-world
      medical settings that serve high numbers of low-income hypertensive African
      Americans with multiple co-morbidity and significant barriers to behavior change.

PMID- 21884618
TI  - Systematic review of safety checklists for use by medical care teams in acute
      hospital settings--limited evidence of effectiveness.
AB  - BACKGROUND: Patient safety is a fundamental component of good quality health
      care. Checklists have been proposed as a method of improving patient safety. This
      systematic review, asked "In acute hospital settings, would the use of safety
      checklists applied by medical care teams, compared to not using checklists,
      improve patient safety?" METHODS: We searched the Cochrane Library, MEDLINE,
      CINAHL, and EMBASE for randomised controlled trials published in English before
      September 2009. Studies were selected and appraised by two reviewers
      independently in consultation with colleagues, using inclusion, exclusion and
      appraisal criteria established a priori. RESULTS: Nine cohort studies with
      historical controls studies from four hospital care settings were included
      intensive care unit, emergency department, surgery, and acute care. The studies
      used a variety of designs of safety checklists, and implemented them in different
      ways, however most incorporated an educational component to teach the staff how
      to use the checklist. The studies assessed outcomes occurring a few weeks to a
      maximum of 12 months post-implementation, and these outcomes were diverse.The
      studies were generally of low to moderate quality and of low levels of evidence,
      with all but one of the studies containing a high risk of bias.The results of
      these studies suggest some improvements in patient safety arising from use of
      safety checklists, but these were not consistent across all studies or for all
      outcomes. Some studies showed no difference in outcomes between checklist use and
      standard care without a checklist. Due to the variations in setting, checklist
      design, educational training given, and outcomes measured, it was unfeasible to
      accurately summarise any trends across all studies. CONCLUSIONS: The included
      studies suggest some benefits of using safety checklists to improve protocol
      adherence and patient safety, but due to the risk of bias in these studies, their
      results should be interpreted with caution. More high quality and studies, are
      needed to enable confident conclusions about the effectiveness of safety
      checklists in acute hospital settings.

PMID- 21884617
TI  - Association of COMT genotypes with S-COMT promoter methylation in growth
      discordant monozygotic twins and healthy adults.
AB  - BACKGROUND: Catechol-O-Methyltransferase (COMT) plays a key role in dopamine and
      estrogen metabolism. Recently, COMT haplotypes rather than the single
      polymorphism Val158Met have been reported to underlie differences in protein
      expression by modulating mRNA secondary structure. So far, studies investigating
      the epigenetic variability of the S-COMT (soluble COMT) promoter region mainly
      focused on phenotypical aspects, and results have been controversial. METHODS: We
      assessed S-COMT promoter methylation in saliva and blood derived DNA with regard
      to early pre- and postnatal growth as well as to genotype for polymorphisms
      rs6269, rs4633, and rs4680 (Val158Met) in 20 monozygotic twin pairs (mean age 4
      years), who were discordant for intrauterine development due to severe feto-fetal
      transfusion syndrome. Methylation levels of two previously reported partially
      methylated cytosines were determined by the quantitative SIRPH (SNuPE- IP RP
      HPLC) assay. RESULTS: Overall, we observed a high variability of S-COMT promoter
      methylation, which did not correlate with individual differences in the pre- or
      postnatal growth pattern. Within the twin pairs however we noted a distinct
      similarity that could be linked to underlying COMT genotypes. This association
      was subsequently confirmed in a cohort of 93 unrelated adult controls.
      Interestingly, 158Val-alleles were found at both ends of the epigenotypical
      range, which is in accordance with a recently proposed model of COMT haplotypes
      corresponding to a continuum of phenotypical variability. CONCLUSION: The strong
      heritable component of S-COMT promoter methylation found in our study needs to be
      considered in future approaches that focus on interactions between COMT
      epigenotype and phenotype.

PMID- 21884619
TI  - The effect of housing on the mental health of older people: the impact of
      lifetime housing history in Whitehall II.
AB  - BACKGROUND: This study describes differences in trajectories of self-reported
      mental health in an ageing cohort, according to their housing, while controlling
      for confounders. METHODS: The General Health Questionnaire was measured on six
      occasions as part of Whitehall II cohort study of office-based British civil
      servants (1985-2009); 10,308 men and women aged 35-55 at baseline. RESULTS: Home
      ownership was the predominant tenure at baseline and increased over the life
      course, but the social gradient remained. In the bivariate analysis, by phase
      nine, renters had higher (poorer mental health) GHQ scores (55.48) than owner
      occupiers (51.98). Those who reported difficulty paying bills or problems with
      housing had higher GHQ scores at baseline (financial difficulties 57.70 vs 54.34;
      house problems 58.06 vs 53.99) and this relative difference increased by phase
      nine (financial difficulties 59.64 vs 51.67; house problems 56.68 vs 51.22). In
      multivariate models, the relative differences in GHQ scores by tenure increased
      with age, but were no longer significant after adjusting for confounders. Whereas
      GHQ scores for those with housing problems and financial difficulties were still
      significantly higher as participants grew older. CONCLUSION: The social gradient
      in the effect of home ownership on mental health, which is evident at baseline,
      diminishes as people get older, whereas housing quality and financial problems
      become relatively more important in explaining older people's health.
      Inequalities in housing quality and ability to deal with household financial
      problems will become increasingly important mental health issues as the
      population ages.

PMID- 21884620
TI  - Clinical bioinformatics: a new emerging science.

PMID- 21884621
TI  - RNA interference against polo-like kinase-1 in advanced non-small cell lung
      cancers.
AB  - Worldwide, approximately one and a half million new cases of lung cancer are
      diagnosed each year, and about 85% of lung cancer are non-small cell lung cancer
      (NSCLC). As the molecular pathogenesis underlying NSCLC is understood, new
      molecular targeting agents can be developed. However, current therapies are not
      sufficient to cure or manage the patients with distant metastasis, and novel
      strategies are necessary to be developed to cure the patients with advanced
      NSCLC.RNA interference (RNAi) is a phenomenon of sequence-specific gene silencing
      in mammalian cells and its discovery has lead to its wide application as a
      powerful tool in post-genomic research. Recently, short interfering RNA (siRNA),
      which induces RNAi, has been experimentally introduced as a cancer therapy and is
      expected to be developed as a nucleic acid-based medicine. Recently, several
      clinical trials of RNAi therapies against cancers are ongoing. In this article,
      we discuss the most recent findings concerning the administration of siRNA
      against polo-like kinase-1 (PLK-1) to liver metastatic NSCLC. PLK-1 regulates the
      mitotic process in mammalian cells. These promising results demonstrate that PLK
      1 is a suitable target for advanced NSCLC therapy.

PMID- 21884622
TI  - Bioinformatic-driven search for metabolic biomarkers in disease.
AB  - The search and validation of novel disease biomarkers requires the complementary
      power of professional study planning and execution, modern profiling technologies
      and related bioinformatics tools for data analysis and interpretation. Biomarkers
      have considerable impact on the care of patients and are urgently needed for
      advancing diagnostics, prognostics and treatment of disease. This survey article
      highlights emerging bioinformatics methods for biomarker discovery in clinical
      metabolomics, focusing on the problem of data preprocessing and consolidation,
      the data-driven search, verification, prioritization and biological
      interpretation of putative metabolic candidate biomarkers in disease. In
      particular, data mining tools suitable for the application to omic data gathered
      from most frequently-used type of experimental designs, such as case-control or
      longitudinal biomarker cohort studies, are reviewed and case examples of selected
      discovery steps are delineated in more detail. This review demonstrates that
      clinical bioinformatics has evolved into an essential element of biomarker
      discovery, translating new innovations and successes in profiling technologies
      and bioinformatics to clinical application.

PMID- 21884623
TI  - Virtual screening, identification and experimental testing of novel inhibitors of
      PBEF1/Visfatin/NMPRTase for glioma therapy.
AB  - BACKGROUND: Pre-B-cell colony enhancing factor 1 gene (PBEF1) encodes
      nicotinamide phosphoribosyltransferase (NMPRTase), which catalyses the rate
      limiting step in the salvage pathway of NAD+ metabolism in mammalian cells. PBEF1
      transcript and protein levels have been shown to be elevated in glioblastoma and
      a chemical inhibitor of NMPRTase has been shown to specifically inhibit cancer
      cells. METHODS: Virtual screening using docking was used to screen a library of
      more than 13,000 chemical compounds. A shortlisted set of compounds were tested
      for their inhibition activity in vitro by an NMPRTase enzyme assay. Further, the
      ability of the compounds to inhibit glioma cell proliferation was carried out.
      RESULTS: Virtual screening resulted in short listing of 34 possible ligands, of
      which six were tested experimentally, using the NMPRTase enzyme inhibition assay
      and further with the glioma cell viability assays. Of these, two compounds were
      found to be significantly efficacious in inhibiting the conversion of
      nicotinamide to NAD+, and out of which, one compound, 3-amino-2-benzyl-7-nitro-4
      (2-quinolyl-)-1,2-dihydroisoquinolin-1-one, was found to inhibit the growth of a
      PBEF1 over expressing glioma derived cell line U87 as well. CONCLUSIONS: Thus, a
      novel inhibitor has been identified through a structure based drug discovery
      approach and is further supported by experimental evidence.

PMID- 21884624
TI  - A base-calling algorithm for Tm-shifted melting curve SNP assay.
AB  - BACKGROUND: Tm-shifted melting curve SNP assays are a class of homogeneous, low
      cost genotyping assays. Alleles manifest themselves as signal peaks in the
      neighbourhood of theoretical allele-specific melting temperatures. Base calling
      for these assays has mostly relied on unsupervised algorithm or human visual
      inspection to date. However, a practical clinical test needs to handle one or few
      individual samples at a time. This could pose a challenge for unsupervised
      algorithms which usually require a large number of samples to define alleles
      representing signal clusters on the fly. METHODS: We presented a supervised base
      calling algorithm and software for Tm-shifted melting curve SNP assays. The
      algorithm comprises a peak detection procedure and an ordinal regression model.
      The peak detection procedure is required for building models as well as handling
      new samples. Ordinal regression is proposed because signal intensities of alleles
      AA, AB, and BB usually follow an ordinal pattern with the heterozygous allele lie
      between two distinct homozygous alleles. Coefficients of the ordinal regression
      model are first trained and then used for base calling. RESULTS: A dataset of 12
      SNPs of 44 unrelated persons was used for a demonstration purpose. The call rate
      is 99.6%. Among the base calls, 99.1% are identical to those made by the
      sequencing method. A small fraction of the melting curve signals (0.4%) is
      declared as "no call" for further human inspection. A software was implemented
      using the Java language, providing a graphical user interface for the
      visualization and handling of multiple melting curve signals. CONCLUSIONS: Tm
      shifted melting curve SNP assays, together with the proposed base calling
      algorithm and software, provide a practical solution for genetic tests on a
      clinical setting. The software is available in
      http://www.bioinformatics.org/mcsnp/wiki/Main/HomePage.

PMID- 21884625
TI  - The NFI-Regulome Database: A tool for annotation and analysis of control regions
      of genes regulated by Nuclear Factor I transcription factors.
AB  - BACKGROUND: Genome annotation plays an essential role in the interpretation and
      use of genome sequence information. While great strides have been made in the
      annotation of coding regions of genes, less success has been achieved in the
      annotation of the regulatory regions of genes, including promoters,
      enhancers/silencers, and other regulatory elements. One reason for this disparity
      in annotated information is that coding regions can be assessed using high
      throughput techniques such as EST sequencing, while annotation of regulatory
      regions often requires a gene-by-gene approach. RESULTS: The NFI-Regulome
      database http://nfiregulome.ccr.buffalo.edu was designed to promote easy
      annotation of the regulatory regions of genes that contain binding sites for the
      NFI (Nuclear Factor I) family of transcription factors, using data from the
      published literature. Binding sites are annotated together with the sequence of
      the gene, obtained from the UCSC Genome site, and the locations of all binding
      sites for multiple genes can be displayed in a number of formats designed to
      facilitate inter-gene comparisons. Classes of genes based on expression pattern,
      disease involvement, or types of binding sites present can be readily compared in
      order to assess common "architectural" structures in the regulatory regions.
      CONCLUSIONS: The NFI-Regulome database allows rapid display of the relative
      locations and number of transcription factor binding sites of individual or
      defined sets of genes that contain binding sites for NFI transcription factors.
      This database may in the future be expanded into a distributed database structure
      including other families of transcription factors. Such databases may be useful
      for identifying common regulatory structures in genes essential for organ
      development, tissue-specific gene expression or those genes related to specific
      diseases.

PMID- 21884626
TI  - Moving towards high density clinical signature studies with a human proteome
      catalogue developing multiplexing mass spectrometry assay panels.
AB  - A perspective overview is given describing the current development of multiplex
      mass spectrometry assay technology platforms utilized for high throughput
      clinical sample analysis. The development of targeted therapies with novel
      personalized medicine drugs will require new tools for monitoring efficacy and
      outcome that will rely on both the quantification of disease progression related
      biomarkers as well as the measurement of disease specific pathway/signaling
      proteins.The bioinformatics developments play a key central role in the area of
      clinical proteomics where targeted peptide expressions in health and disease are
      investigated in small-, medium- and large-scaled clinical studies.An outline is
      presented describing applications of the selected reaction monitoring (SRM) mass
      spectrometry assay principle. This assay form enables the simultaneous
      description of multiple protein biomarkers and is an area under a fast and
      progressive development throughout the community. The Human Proteome
      Organization, HUPO, recently launched the Human Proteome Project (HPP) that will
      map the organization of proteins on specific chromosomes, on a chromosome-by
      chromosome basis utilizing the SRM technology platform. Specific examples of an
      SRM-multiplex quantitative assay platform dedicated to the cardiovascular disease
      area, screening Apo A1, Apo A4, Apo B, Apo CI, Apo CII, Apo CIII, Apo D, Apo E,
      Apo H, and CRP biomarkers used in daily diagnosis routines in clinical hospitals
      globally, are presented. We also provide data on prostate cancer studies that
      have identified a variety of PSA isoforms characterized by high-resolution
      separation interfaced to mass spectrometry.

PMID- 21884627
TI  - Roles of XB130, a novel adaptor protein, in cancer.
AB  - Adaptor proteins, with multi-modular structures, can participate in the
      regulation of various cellular functions. During molecular cloning process of
      actin filament associated protein, we have discovered a novel adaptor protein,
      referred to as XB130. The human xb130 gene is localized on chromosome 10q25.3,
      and encodes an 818 amino acid protein. The N-terminal region of XB130 includes
      several tyrosine phosphorylation sites and a proline-rich sequence that might
      interact with Src homology 2 and 3 domain-containing proteins, respectively. Our
      studies have indeed implicated XB130 as a likely substrate and regulator of
      tyrosine kinase-mediated signaling. Down-regulation of endogenous XB130 with
      small interfering RNA reduced c-Src activity, IL-8 production and phosphorylation
      of Akt in human lung epithelial cells. Further, XB130 binds the p85alpha subunit
      of phosphatidyl-inositol-3-kinase and subsequently mediates signaling through
      RET/PTC in thyroid cancer cells. Knockdown of XB130 using small interfering RNA
      inhibited G1-S phase progression, induced spontaneous apoptosis and enhanced
      intrinsic and extrinsic apoptotic stimulus-induced cell death in human lung and
      thyroid cancer cells. Growth of tumors in nude mice formed from XB130 short
      hairpin RNA stably transfected human thyroid cancer cells were significantly
      reduced, with decreased cell proliferation and increased apoptosis. Further,
      XB130 has a high affinity to lamellipodial F-actin meshwork and is involved in
      the motility and invasiveness of cancer cells. Gene expression profiling
      identified 246 genes significantly changed in XB130 short hairpin RNA transfected
      thyroid cancer cells. Among them, 57 genes are related to cell proliferation or
      survival, including many transcription regulators. Pathway analysis showed that
      the top ranked disease related to XB130 is Cancer, and the top molecular and
      cellular functions are Cellular Growth and Proliferation, and Cell Cycle. These
      observations suggest that the expression of XB130 may affect cell proliferation,
      survival, motility and invasion in various cancer cells. A deeper understanding
      of these mechanisms may lead to the discovery of XB130 as an important mediator
      in tumor development and as a novel therapeutic target for cancer.

PMID- 21884628
TI  - A filter-based feature selection approach for identifying potential biomarkers
      for lung cancer.
AB  - BACKGROUND: Lung cancer is the leading cause of death from cancer in the world
      and its treatment is dependant on the type and stage of cancer detected in the
      patient. Molecular biomarkers that can characterize the cancer phenotype are thus
      a key tool in planning a therapeutic response. A common protocol for identifying
      such biomarkers is to employ genomic microarray analysis to find genes that show
      differential expression according to disease state or type. Data-mining
      techniques such as feature selection are often used to isolate, from among a
      large manifold of genes with differential expression, those specific genes whose
      differential expression patterns are of optimal value in phenotypic
      differentiation. One such technique, Biomarker Identifier (BMI), has been
      developed to identify features with the ability to distinguish between two data
      groups of interest, which is thus highly applicable for such studies. RESULTS:
      Microarray data with validated genes was used to evaluate the utility of BMI in
      identifying markers for lung cancer. This data set contains a set of 129 gene
      expression profiles from large-airway epithelial cells (60 samples from smokers
      with lung cancer and 69 from smokers without lung cancer) and 7 genes from this
      data have been confirmed to be differentially expressed by quantitative PCR.
      Using this data set, BMI was compared with various well-known feature selection
      methods and was found to be more successful than other methods in finding useful
      genes to classify cancerous samples. Also it is evident that genes selected by
      BMI (given the same number of genes and classification algorithms) showed better
      discriminative power than those from the original study. After pathway analysis
      on the selected genes by BMI, we have been able to correlate the selected genes
      with well-known cancer-related pathways. CONCLUSIONS: Our results show that BMI
      can be used to analyze microarray data and to find useful genes for classifying
      samples. Pathway analysis suggests that BMI is successful in identifying
      biomarker-quality cancer-related genes from the data.

PMID- 21884630
TI  - BioBanking - The Holy Grail of novel drug and diagnostic developments?
AB  - The ever increasing social cost that society pays for illness and disease are
      currently steadily increasing in many countries in the world today. These changes
      in society becomes a major financial burden that activates politicians and health
      care organizations in order to find new solutions. Biobanks are becoming the new
      powerful modality within the field of modern Life Science, that is expected to be
      important in the proactive awareness of patient health status. Biobanks are also
      expected to promote the developments of targeted treatments with personalized
      indicator assays, for effective use of Personalized Medicine treatments in the
      near future.

PMID- 21884629
TI  - Peripheral blood gene expression profiles in COPD subjects.
AB  - To identify non-invasive gene expression markers for chronic obstructive
      pulmonary disease (COPD), we performed genome-wide expression profiling of
      peripheral blood samples from 12 subjects with significant airflow obstruction
      and an equal number of non-obstructed controls. RNA was isolated from Peripheral
      Blood Mononuclear Cells (PBMCs) and gene expression was assessed using Affymetrix
      U133 Plus 2.0 arrays.Tests for gene expression changes that discriminate between
      COPD cases (FEV1< 70% predicted, FEV1/FVC < 0.7) and controls (FEV1> 80%
      predicted, FEV1/FVC > 0.7) were performed using Significance Analysis of
      Microarrays (SAM) and Bayesian Analysis of Differential Gene Expression (BADGE).
      Using either test at high stringency (SAM median FDR = 0 or BADGE p < 0.01) we
      identified differential expression for 45 known genes. Correlation of gene
      expression with lung function measurements (FEV1 & FEV1/FVC), using both Pearson
      and Spearman correlation coefficients (p < 0.05), identified a set of 86 genes. A
      total of 16 markers showed evidence of significant correlation (p < 0.05) with
      quantitative traits and differential expression between cases and controls. We
      further compared our peripheral gene expression markers with those we previously
      identified from lung tissue of the same cohort. Two genes, RP9and NAPE-PLD, were
      identified as decreased in COPD cases compared to controls in both lung tissue
      and blood. These results contribute to our understanding of gene expression
      changes in the peripheral blood of patients with COPD and may provide insight
      into potential mechanisms involved in the disease.

PMID- 21884631
TI  - Frontiers of oncology: biobanking resources for the 21st century.

PMID- 21884632
TI  - Functional similarity analysis of human virus-encoded miRNAs.
AB  - miRNAs are a class of small RNAs that regulate gene expression via RNA silencing
      machinery. Some viruses also encode miRNAs, contributing to the complex virus
      host interactions. A better understanding of viral miRNA functions would be
      useful in designing new preventive strategies for treating diseases induced by
      viruses. To meet the challenge for how viruses module host gene expression by
      their encoded miRNAs, we measured the functional similarities among human viral
      miRNAs by using a method we reported previously. Higher order functions regulated
      by viral miRNAs were also identified by KEGG pathway analysis on their targets.
      Our study demonstrated the biological processes involved in virus-host
      interactions via viral miRNAs. Phylogenetic analysis suggested that viral miRNAs
      have distinct evolution rates compared with their corresponding genome.

PMID- 21884633
TI  - Quantitative analysis of histone exchange for transcriptionally active chromatin.
AB  - BACKGROUND: Genome-wide studies use techniques, like chromatin
      immunoprecipitation, to purify small chromatin sections so that protein-protein
      and protein-DNA interactions can be analyzed for their roles in modulating gene
      transcription. Histone post-translational modifications (PTMs) are key regulators
      of gene transcription and are therefore prime targets for these types of studies.
      Chromatin purification protocols vary in the amount of chemical cross-linking
      used to preserve in vivo interactions. A balanced level of chemical cross-linking
      is required to preserve the native chromatin state during purification, while
      still allowing for solubility and interaction with affinity reagents. FINDINGS:
      We previously used an isotopic labeling technique combining affinity purification
      and mass spectrometry called transient isotopic differentiation of interactions
      as random or targeted (transient I-DIRT) to identify the amounts of chemical
      cross-linking required to prevent histone exchange during chromatin purification.
      New bioinformatic analyses reported here reveal that histones containing
      transcription activating PTMs exchange more rapidly relative to bulk histones and
      therefore require a higher level of cross-linking to preserve the in vivo
      chromatin structure. CONCLUSIONS: The bioinformatic approach described here is
      widely applicable to other studies requiring the analysis and purification of
      cognate histones and their modifications. Histones containing PTMs correlated to
      active gene transcription exchange more readily than bulk histones; therefore, it
      is necessary to use more rigorous in vivo chemical cross-linking to stabilize
      these marks during chromatin purification.

PMID- 21884634
TI  - Discovering and validating unknown phospho-sites from p38 and HuR protein kinases
      in vitro by Phosphoproteomic and Bioinformatic tools.
AB  - BACKGROUND: The mitogen activated protein kinase (MAPK) pathways are known to be
      deregulated in many human malignancies. Phosphopeptide identification of protein
      kinases and site determination are major challenges in biomedical mass
      spectrometry (MS). P38 and HuR protein kinases have been reported extensively in
      the general principles of signalling pathways modulated by phosphorylation,
      mainly by molecular biology and western blotting techniques. Thus, although it
      has been demonstrated they are phosphorylated in different stress/stimuli
      conditions, the phosphopeptides and specific amino acids in which the phosphate
      groups are located in those protein kinases have not been shown completely.
      METHODS: We have combined different resins: (a) IMAC (Immobilized Metal Affinity
      Capture), (b) TiO2 (Titanium dioxide) and (c) SIMAC (Sequential Elution from
      IMAC) to isolate phosphopeptides from p38 and HuR protein kinases in
      vitro.Different phosphopeptide MS strategies were carried out by the LTQ ion Trap
      mass spectrometer (Thermo): (a) Multistage activation (MSA) and (b) Neutral loss
      MS3 (DDNLMS3).In addition, Molecular Dynamics (MD) bioinformatic simulation has
      been applied in order to simulate, over a period of time, the effects of the
      presence of the extra phosphate group (and the associated negative charge) in the
      overall structure and behaviour of the protein HuR.This study is supported by the
      Declaration of Helsinki and subsequent ethical guidelines. RESULTS: The
      combination of these techniques allowed for:(1) The identification of 6 unknown
      phosphopeptides of these protein kinases. (2) Amino acid site assignments of the
      phosphate groups from each identified phosphopeptide, including manual validation
      by inspection of all the spectra. (3) The analyses of the phosphopeptides
      discovered were carried out in four triplicate experiments to avoid false
      positives getting high reproducibility in all the isolated phosphopeptides
      recovered from both protein kinases. (4) Computer simulation using MD techniques
      allowed us to get functional models of both structure and interactions of the
      previously mentioned phosphorylated kinases and the differences between their
      phosphorylated and un-phosphorylated forms. CONCLUSION: Many research studies are
      necessary to unfold the whole signalling network (human proteome), which is so
      important to advance in clinical research, especially in the cases of malignant
      diseases.

PMID- 21884635
TI  - Data mining of mental health issues of non-bone marrow donor siblings.
AB  - BACKGROUND: Allogenic hematopoietic stem cell transplantation is a curative
      treatment for patients with advanced hematologic malignancies. However, the long
      term mental health issues of siblings who were not selected as donors (non-donor
      siblings, NDS) in the transplantation have not been well assessed. Data mining is
      useful in discovering new findings from a large, multidisciplinary data set and
      the Scenario Map analysis is a novel approach which allows extracting keywords
      linking different conditions/events from text data of interviews even when the
      keywords appeared infrequently. The aim of this study is to assess mental health
      issues on NDSs and to find helpful keywords for the clinical follow-up using a
      Scenario Map analysis. FINDINGS: A 47-year-old woman whose younger sister had
      undergone allogenic hematopoietic stem cell transplantation 20 years earlier was
      interviewed as a NDS. The text data from the interview transcriptions was
      analyzed using Scenario Mapping. Four clusters of words and six keywords were
      identified. Upon review of the word clusters and keywords, both the subject and
      researchers noticed that the subject has had mental health issues since the
      disease onset to date with being a NDS. The issues have been alleviated by her
      family. CONCLUSIONS: This single subject study suggested the advantages of data
      mining in clinical follow-up for mental health issues of patients and/or their
      families.

PMID- 21884637
TI  - Automated generation of massive image knowledge collections using Microsoft Live
      Labs Pivot to promote neuroimaging and translational research.
AB  - BACKGROUND: Massive datasets comprising high-resolution images, generated in
      neuro-imaging studies and in clinical imaging research, are increasingly
      challenging our ability to analyze, share, and filter such images in clinical and
      basic translational research. Pivot collection exploratory analysis provides each
      user the ability to fully interact with the massive amounts of visual data to
      fully facilitate sufficient sorting, flexibility and speed to fluidly access,
      explore or analyze the massive image data sets of high-resolution images and
      their associated meta information, such as neuro-imaging databases from the Allen
      Brain Atlas. It is used in clustering, filtering, data sharing and classifying of
      the visual data into various deep zoom levels and meta information categories to
      detect the underlying hidden pattern within the data set that has been used.
      METHOD: We deployed prototype Pivot collections using the Linux CentOS running on
      the Apache web server. We also tested the prototype Pivot collections on other
      operating systems like Windows (the most common variants) and UNIX, etc. It is
      demonstrated that the approach yields very good results when compared with other
      approaches used by some researchers for generation, creation, and clustering of
      massive image collections such as the coronal and horizontal sections of the
      mouse brain from the Allen Brain Atlas. RESULTS: Pivot visual analytics was used
      to analyze a prototype of dataset Dab2 co-expressed genes from the Allen Brain
      Atlas. The metadata along with high-resolution images were automatically
      extracted using the Allen Brain Atlas API. It is then used to identify the hidden
      information based on the various categories and conditions applied by using
      options generated from automated collection. A metadata category like chromosome,
      as well as data for individual cases like sex, age, and plan attributes of a
      particular gene, is used to filter, sort and to determine if there exist other
      genes with a similar characteristics to Dab2. And online access to the mouse
      brain pivot collection can be viewed using the link http://edtech
      dev.uthsc.edu/CTSI/teeDev1/unittest/PaPa/collection.html (user name: tviangte and
      password: demome) CONCLUSIONS: Our proposed algorithm has automated the creation
      of large image Pivot collections; this will enable investigators of clinical
      research projects to easily and quickly analyse the image collections through a
      perspective that is useful for making critical decisions about the image patterns
      discovered.

PMID- 21884636
TI  - FISH Oracle: a web server for flexible visualization of DNA copy number data in a
      genomic context.
AB  - BACKGROUND: The rapidly growing amount of array CGH data requires improved
      visualization software supporting the process of identifying candidate cancer
      genes. Optimally, such software should work across multiple microarray platforms,
      should be able to cope with data from different sources and should be easy to
      operate. RESULTS: We have developed a web-based software FISH Oracle to visualize
      data from multiple array CGH experiments in a genomic context. Its fast
      visualization engine and advanced web and database technology supports highly
      interactive use. FISH Oracle comes with a convenient data import mechanism,
      powerful search options for genomic elements (e.g. gene names or karyobands),
      quick navigation and zooming into interesting regions, and mechanisms to export
      the visualization into different high quality formats. These features make the
      software especially suitable for the needs of life scientists. CONCLUSIONS: FISH
      Oracle offers a fast and easy to use visualization tool for array CGH and SNP
      array data. It allows for the identification of genomic regions representing
      minimal common changes based on data from one or more experiments. FISH Oracle
      will be instrumental to identify candidate onco and tumor suppressor genes based
      on the frequency and genomic position of DNA copy number changes. The FISH Oracle
      application and an installed demo web server are available at http://www.zbh.uni
      hamburg.de/fishoracle.

PMID- 21884638
TI  - Nothing to do and all day to do it in.

PMID- 21884639
TI  - Building effective critical care teams.
AB  - Critical care is formulated and delivered by a team. Accordingly, behavioral
      scientific principles relevant to teams, namely psychological safety, transactive
      memory and leadership, apply to critical care teams. Two experts in behavioral
      sciences review the impact of psychological safety, transactive memory and
      leadership on medical team outcomes. A clinician then applies those principles to
      two routine critical care paradigms: daily rounds and resuscitations. Since
      critical care is a team endeavor, methods to maximize teamwork should be learned
      and mastered by critical care team members, and especially leaders.

PMID- 21884640
TI  - Vitamin D and breast cancer: interpreting current evidence.
AB  - Preclinical investigations and selected clinical observational studies support an
      association between higher vitamin D intake and 25-hydroxyvitamin D levels with
      lower breast cancer risk. However, the recently updated report from the Institute
      of Medicine concluded that, for cancer and vitamin D, the evidence was
      'inconsistent and insufficient to inform nutritional requirements'. Against this
      background, reports examining vitamin D intake, 25-hydroxyvitamin D levels and
      breast cancer incidence and outcome were reviewed. Current evidence supports the
      pursuit of several research questions but not routine 25-hydroxyvitamin D
      monitoring and vitamin D supplementation to reduce breast cancer incidence or
      improve breast cancer outcome.

PMID- 21884641
TI  - Choosing the right cell line for breast cancer research.
AB  - Breast cancer is a complex and heterogeneous disease. Gene expression profiling
      has contributed significantly to our understanding of this heterogeneity at a
      molecular level, refining taxonomy based on simple measures such as histological
      type, tumour grade, lymph node status and the presence of predictive markers like
      oestrogen receptor and human epidermal growth factor receptor 2 (HER2) to a more
      sophisticated classification comprising luminal A, luminal B, basal-like, HER2
      positive and normal subgroups. In the laboratory, breast cancer is often modelled
      using established cell lines. In the present review we discuss some of the issues
      surrounding the use of breast cancer cell lines as experimental models, in light
      of these revised clinical classifications, and put forward suggestions for
      improving their use in translational breast cancer research.

PMID- 21884642
TI  - Poly(ADP-ribose) polymerase inhibition: a new direction for BRCA and triple
      negative breast cancer?
AB  - Inhibitors of poly(ADP-ribose) polymerase (PARP)-mediated DNA repair have shown
      promise in early clinical studies in the treatment of specific subgroups of
      breast cancer. Notably, phase II trials indicate that olaparib, an oral PARP
      inhibitor, has activity as a single agent in BRCA-related tumours, and that a
      combination of iniparib, an intravenous PARP inhibitor, and chemotherapy offers a
      survival advantage, compared with chemotherapy alone, in triple-negative breast
      cancer. Phase III data on the latter indication are expected in 2011.
      Intriguingly, iniparib does not increase toxicity when used as a chemo
      potentiating agent, suggesting that it differs in its mechanism of action from
      other agents in this class. Overall, PARP inhibitors represent a potentially
      important new class of anti-cancer agents with two potential modes of action, as
      single agents causing synthetic lethality and as chemo-potentiating agents.

PMID- 21884643
TI  - The 'alternative' EMT switch.
AB  - Epithelial to mesenchymal transition (EMT) is an essential process in embryonic
      development and is aberrantly induced in many disease settings. Work carried out
      by Chonghui Cheng's laboratory addressed the involvement of alternative RNA
      splicing in EMT and its link to tumour progression. They describe a switch in
      CD44 expression from variant isoform(s) to the standard isoform and showed, for
      the first time, that this is required for normal epithelial cells to undergo EMT.
      In addition, they link expression of the CD44 standard isoform with high-grade
      breast cancer and to activation of the phosphoinositide 3-kinase/Akt pathway and
      apoptosis resistance in a mouse model of recurrent disease.

PMID- 21884644
TI  - Cannibalism, cell survival, and endocrine resistance in breast cancer.
AB  - Breast cancer cells often respond to an endocrine therapy by altering expression
      of specific estrogen-responsive genes and inducing autophagy, a cannibalistic
      lysosomal pathway. Autophagy eliminates damaged or other organelles, allowing the
      recovery of the energy stored in their macromolecules to attempt restoration of
      metabolic homeostasis. Induction of autophagy can result from activation of the
      unfolded protein response following metabolic stress, the final cell fate often
      being determined by the extent and duration of autophagy. A study by Gonzalez
      Malerva and colleagues builds upon this extensive knowledge, adding HSPB8 to the
      list of altered genes associated with endocrine resistance in breast cancer and
      describing the ability of HSPB8 to regulate autophagy and confer tamoxifen
      resistance.

PMID- 21884645
TI  - Clinical review: Update on hemodynamic monitoring--a consensus of 16.
AB  - Hemodynamic monitoring plays a fundamental role in the management of acutely ill
      patients. With increased concerns about the use of invasive techniques, notably
      the pulmonary artery catheter, to measure cardiac output, recent years have seen
      an influx of new, less-invasive means of measuring hemodynamic variables, leaving
      the clinician somewhat bewildered as to which technique, if any, is best and
      which he/she should use. In this consensus paper, we try to provide some
      clarification, offering an objective review of the available monitoring systems,
      including their specific advantages and limitations, and highlighting some key
      principles underlying hemodynamic monitoring in critically ill patients.

PMID- 21884649
TI  - Genetic risk factors for celiac disease.

PMID- 21884650
TI  - Genetic risk factors for celiac disease.

PMID- 21884646
TI  - Bench-to-bedside review: Ventilation-induced renal injury through systemic
      mediator release--just theory or a causal relationship?
AB  - We review the current literature on the molecular mechanisms involved in the
      pathogenesis of acute kidney injury induced by plasma mediators released by
      mechanical ventilation. A comprehensive literature search in the PubMed database
      was performed and articles were identified that showed increased plasma levels of
      mediators where the increase was solely attributable to mechanical ventilation. A
      subsequent search revealed articles delineating the potential effects of each
      mediator on the kidney or kidney cells. Limited research has focused specifically
      on the relationship between mechanical ventilation and acute kidney injury. Only
      a limited number of plasma mediators has been implicated in mechanical
      ventilation-associated acute kidney injury. The number of mediators released
      during mechanical ventilation is far greater and includes pro- and anti
      inflammatory mediators, but also mediators involved in coagulation, fibrinolysis,
      cell adhesion, apoptosis and cell growth. The potential effects of these
      mediators is pleiotropic and include effects on inflammation, cell recruitment,
      adhesion and infiltration, apoptosis and necrosis, vasoactivity, cell
      proliferation, coagulation and fibrinolysis, transporter regulation, lipid
      metabolism and cell signaling. Most research has focused on inflammatory and
      chemotactic mediators. There is a great disparity of knowledge of potential
      effects on the kidney between different mediators. From a theoretical point of
      view, the systemic release of several mediators induced by mechanical ventilation
      may play an important role in the pathophysiology of acute kidney injury.
      However, evidence supporting a causal relationship is lacking for the studied
      mediators.

PMID- 21884647
TI  - Prevalence of ocular signs and subclinical vitamin A deficiency and its
      determinants among rural pre-school children in India.
AB  - OBJECTIVE: To assess the magnitude and determinants of vitamin A deficiency (VAD)
      and coverage of vitamin A supplementation (VAS) among pre-school children.
      DESIGN: A community-based cross-sectional study was carried out by adopting a
      multistage, stratified, random sampling procedure. SETTING: Rural areas of eight
      states in India. SUBJECTS: Pre-school children and their mothers were covered.
      RESULTS: A total of 71,591 pre-school children were clinically examined for
      ocular signs of VAD. Serum retinol concentrations in dried blood spots were
      assessed in a sub-sample of 3954 children using HPLC. The prevalence of Bitot
      spots was 0.8%. The total ocular signs were significantly higher (P < 0.001)
      among boys (2.6%) compared with girls (1.9%) and in older children (3-4 years)
      compared (P < 0.001) with younger (1-2 years), and were also high in children of
      labourers, scheduled castes and illiterate mothers. The odds of having Bitot
      spots was highest in children of scheduled caste (OR = 3.8; 95% CI 2.9, 5.0),
      labourers (OR = 2.9; 95% CI 2.1, 3.9), illiterate mothers (OR = 2.7; 95% CI 2.2,
      2.3) and households without a sanitary latrine (OR = 5.9; 95% CI 4.0, 8.7).
      Subclinical VAD (serum retinol level <20 MUg/dl) was observed in 62% of children.
      This was also relatively high among scheduled caste and scheduled tribe children.
      The rate of coverage of VAS was 58%. CONCLUSIONS: The study revealed that VAD is
      a major nutritional problem and coverage of VAS was poor. The important
      determinants of VAD were illiteracy, low socio-economic status, occupation and
      poor sanitation. Strengthening the existing VAS programme and focused attention
      on dietary diversification are essential for prevention of VAD.

PMID- 21884651
TI  - Does ultrasonic dental equipment affect cardiovascular implantable electronic
      devices?

PMID- 21884652
TI  - What should I look for when treating an alcoholic patient (current or recovered)
      in my office?

PMID- 21884653
TI  - Oral lesion on dorsum of tongue.

PMID- 21884654
TI  - "Now we got lots to eat and they're telling us not to eat it": understanding
      changes to south-east Labrador Inuit relationships to food.
AB  - OBJECTIVES: Culture, history and social circumstances shape how people understand
      their relationships to food, what foods are eaten, when, how much and how often.
      This ultimately shapes overall health. This study aims to connect research about
      food, culture and health by positioning south-eastern Labrador Inuit
      understandings of food at the forefront of how we begin to address chronic
      disease within southeastern Labrador Inuit communities. STUDY DESIGN: This study
      collected stories about food from 3 generations of men and women who live in the
      south-east Labrador Inuit community of St. Lewis, Newfoundland and Labrador.
      METHODS: Qualitative interviews (n=24) and 1 focus group (n=8) were conducted
      with 3 generations of men and women who were asked to share stories about how
      they experience and understand their relationships to food. RESULTS: Local plants
      and animals have historically been used for shelter, clothing and medicines, and
      their procurement provided opportunities for physical activity, sharing with
      others and passing along generational knowledge. The historical absence of
      government services has meant that stable food supplies were unavailable; local
      sources of food have, until the recent past, been essential for survival. The
      significant change over a short period, from having to ensure that one has enough
      to eat and avoiding nutritional deficiencies, to having both healthy and
      unhealthy food choices constantly available, has required a different "way" of
      understanding food. CONCLUSIONS: It is imperative that nutrition programs and
      resources directed towards improving the health of south-east Labrador Inuit take
      into account how cultural, historical and social circumstances have shaped south
      east Labrador Inuit understandings of food.

PMID- 21884655
TI  - Community-based health research led by the Vuntut Gwitchin First Nation.
AB  - OBJECTIVES: This paper documents an exceptional research partnership developed
      between the Vuntut Gwitchin Government (VGG) in Old Crow, Yukon, with a group of
      scientists to examine northern food security and health as part of a larger,
      multidisciplinary International Polar Year (IPY) research program. We focus on
      the elements that enabled a successful community-researcher relationship. Study
      design. The VGG led the development of the research and acted as Principal
      Investigator on the IPY grant. The multidisciplinary collaboration spanned the
      physical, biological and health sciences, including issues related to food
      security. METHODS: The food security and health component of this research was
      carried out using a series of complementary methods, including focus groups,
      structured interviews, a household questionnaire, an interactive workshop,
      community meetings, transcript analysis and a caribou flesh exposure assessment.
      RESULTS: Results from the food security component are informing local and
      regional adaptation planning. The legacy of the research collaboration includes a
      number of results-based outputs for a range of stakeholders, a community-based
      environmental monitoring program, long-term research relationships and improved
      community capacity. CONCLUSIONS: The type of collaboration described here
      provides a useful model for new types of participatory health research with
      northern communities.

PMID- 21884656
TI  - Identification of risk factors by systematic review and development of risk
      adjusted models for surgical site infection.
AB  - BACKGROUND: Surgical site infections (SSIs) are complications of surgery that
      cause significant postoperative morbidity. SSI has been proposed as a potential
      indicator of the quality of care in the context of clinical governance and
      monitoring of the performance of NHS organisations against targets. OBJECTIVES:
      We aimed to address a number of objectives. Firstly, identify risk factors for
      SSI, criteria for stratifying surgical procedures and evidence about the
      importance of postdischarge surveillance (PDS). Secondly, test the importance of
      risk factors for SSI in surveillance databases and investigate interactions
      between risk factors. Thirdly, investigate and validate different definitions of
      SSI. Lastly, develop models for making risk-adjusted comparisons between
      hospitals. DATA SOURCES: A single hospital surveillance database was used to
      address objectives 2 and 3 and the UK Surgical Site Infection Surveillance
      Service database to address objective 4. STUDY DESIGN: There were four elements
      to the research: (1) systematic reviews of risk factors for SSI (two reviewers
      assessed titles and abstracts of studies identified by the search strategy and
      the quality of studies was assessed using the Newcastle Ottawa Scale); (2)
      assessment of agreement between four SSI definitions; (3) validation of
      definitions of SSI, quantifying their ability to predict clinical outcomes; and
      (4) development of operation-specific risk models for SSI, with hospitals fitted
      as random effects. RESULTS: Reviews of SSI risk factors other than established
      SSI risk indices identified other risk; some were operation specific, but others
      applied to multiple operations. The factor most commonly identified was duration
      of preoperative hospital stay. The review of PDS for SSI confirmed the need for
      PDS if SSIs are to be compared meaningfully over time within an institution.
      There was wide variation in SSI rate (SSI%) using different definitions. Over
      twice as many wounds were classified as infected by one definition only as were
      classified as infected by both. Different SSI definitions also classified
      different wounds as being infected. The two most established SSI definitions had
      broadly similar ability to predict the chosen clinical outcomes. This finding is
      paradoxical given the poor agreement between definitions. Elements of each
      definition not common to both may be important in predicting clinical outcomes or
      outcomes may depend on only a subset of elements which are common to both. Risk
      factors fitted in multivariable models and their effects, including age and
      gender, varied by surgical procedure. Operative duration was an important risk
      factor for all operations, except for hip replacement. Wound class was included
      least often because some wound classes were not applicable to all operations or
      were combined because of small numbers. The American Association of
      Anesthesiologists class was a consistent risk factor for most operations.
      CONCLUSIONS: The research literature does not allow surgery-specific or generic
      risk factors to be defined. SSI definitions varied between surveillance
      programmes and potentially between hospitals. Different definitions do not have
      good agreement, but the definitions have similar ability to predict outcomes
      influenced by SSI. Associations between components of the National Nosocomial
      Infections Surveillance risk index and odds of SSI varied for different surgical
      procedures. There was no evidence for effect modification by hospital. Estimates
      of SSI% should be disseminated within institutions to inform infection control.
      Estimates of SSI% across institutions or countries should be interpreted
      cautiously and should not be assumed to reflect quality of medical care. Future
      research should focus on developing an SSI definition that has satisfactory
      psychometric properties, that can be applied in everyday clinical settings,
      includes PDS and is formulated to detect SSIs that are important to patients or
      health services. FUNDING: The National Institute for Health Research Technology
      Assessment programme.

PMID- 21884657
TI  - [Pregnancy complications].

PMID- 21884658
TI  - [Severe increase in alkaline phosphatase levels during pregnancy].
AB  - In pregnancy the maternal serum alkaline phosphatase (AP) level increases
      twofold. If AP values rise above this level, diseases should be considered. We
      report a case of a 29 year-old pregnant woman with a ninefold increase in the
      serum AP level due to an increase in the placental level. In the last trimester
      she had a deep venous thrombosis and lung emboli, which is, however, not shown to
      correlate to a rise in the AP level. She delivered uncomplicated at term. The aim
      of this case report is to show the increase of the AP level in pregnancy, to show
      that there are different isozymes of AP, and to show the importance of
      investigating a serum AP level, which is increased more than twofold.

PMID- 21884659
TI  - [Blood pressure lowering efficacy of beta-blockers added to monotherapy with a
      thiazid or a calcium antagonist--a survey of a Cochrane review].
AB  - A blood pressure fall of 6-8/4-6 mmHg is seen when a beta-blocker is added to a
      thiazid or a calcium antagonist. Due to less protection against cardiovascular
      complications, most likely explained by an insufficient reduction in the central
      aortic blood pressure profile betablockers, especially atenolol, is no longer
      first choice treatment for hypertension, unless ischaemic heart disease or heart
      failure is present.

PMID- 21884660
TI  - [5-aminosalicylic acid for induction of remission or clinical response in Crohn's
      disease--a survey of a Cochrane review].
AB  - A systematic review to evaluate the efficacy of 5-aminosalicylates for induction
      of remission or clinical response in patients with mild to moderately active
      Crohn's disease is described. The effect of either high (3 to 4.5 g/day) or low
      dose (1 to 2 g/day) 5-aminosalicylic acid was similar to that of placebo.
      Overall, sulfasalazine was not superior to placebo and was inferior to
      glucocorticoids for the treatment of mild to moderately active Crohn's disease.
      Neither published nor unpublished data support any use of 5-aminosalicylates for
      the treatment of Crohn's disease.

PMID- 21884661
TI  - [Restless legs syndrome and depression].
AB  - Epidemiological studies report an odds ratio of 2-4 for major depression among
      patients with restless legs syndrome (RLS) compared with healthy controls. Also a
      high prevalence of RLS in populations of depressed patients is seen. Several
      possible explanations are proposed, such as dopamine dysfunction, sleep
      disturbances, shared diagnostic criteria and adverse effects of antidepressive
      treatment. There is a low degree of evidence for a treatment strategy when
      depression and RLS coexist. Furthermore, it is important to realize, that some
      antidepressants can induce or worsen RLS.

PMID- 21884662
TI  - [Asthma is an epidemic].
AB  - Asthma is a frequent illness in young adults and is characterized by airway hyper
      responsiveness (AHR) and airway inflammation. Asthma is a complex disease and AHR
      as well as inflammation may be limited, although characteristic symptoms are
      present. The clinical experience in asthma treatment is that not all asthmatics
      have a satisfactory effect of the different drugs. Asthma has been found to
      develop from one disease to a multifaceted disease with numerous different
      possibilities. More research is needed in strategic asthma management in the
      search for tailored treatment strategy.

PMID- 21884663
TI  - [Ketamine is used again by both physicians and addicts].
AB  - Ketamine is a unique anaesthetic because it has both hypnotic and analgesic
      effects and also potential hallucinogenic side effects. Lack of cardiopulmonary
      depression makes the drug a popular choice for anaesthesia in the prehospital
      setting. In recent years ketamine has been found to have anti-hyperalgesic and
      opioid saving effects, opening to new ways of managing post-operative and chronic
      pain states. Recreational use of ketamine among night clubbers is increasing and
      makes acute and chronic symptoms of ketamine abuse a new challenge in emergency
      departments.

PMID- 21884664
TI  - [Antibiotics can ameliorate circulatory complications of liver cirrhosis].
AB  - Livercirrhosis can be complicated by a hyperdynamic circulatory syndrome. This is
      due to translocation of bacteria and bacterial product (bacterial DNA and
      endotoxins), which stimulate the splanchnic nitric oxide synthase and leads to
      splanchnic vasodilatation and haemodynamic derangement. This review focuses on
      how broad spectrum antibiotics can ameliorate the haemodynamic consequences of
      bacterial translocation. It is possible that the use of broad spectrum
      antibiotics in the future may be used to prevent other complications of liver
      cirrhosis than spontaneous bacterial peritonitis and infections after
      gastrointestinal bleeding.

PMID- 21884665
TI  - [Presentation of atypical bullous pyoderma gangrenosum].
AB  - Pyoderma gangrenosum (PG) is a rare, ulcerative skin disease. Atypical PG is
      characterized by rapidly evolving painful vesicles and enlarging bullae. Minor
      trauma or surgery is considered the cause in 25-50% of PG lesions. PG often
      mimics necrotizing infection and may therefore be inadequately treated. We
      present a patient with rapidly progressing bullous PG. The lesions were initially
      treated surgically, which led to exacerbation of the ulcers. A decision of
      surgery should be preceded by bacterial culture and microscopy and in case of
      uncertain diagnosis also by histopathologic examination.

PMID- 21884666
TI  - [Topical negative pressure and skin transplantation for the treatment of pyoderma
      gangrenosum].
AB  - Pyoderma gangrenosum (PG) is a rare idiopathic, autoimmune and inflammatory
      disease characterized by the development of ulcerative skin lesions. A 58 year
      old woman, diagnosed with biopsy-verified PG was admitted to the Wound Center at
      Odense University Hospital, with rapid progression of painful, necrotic PG
      lesions on both crura. The lesions were treated, in collaboration with the
      dermatologists, with systemic steroids, topical negative pressure treatments and
      surgical revision in addition to partial skin graft with good results. Following
      the treatment the patient has been pain free and without recurrence for 11
      months.

PMID- 21884667
TI  - [Congenital methaemoglobinaemia--a rare cause of dyspnoea and cyanosis].
AB  - Dyspnoea in young people often leads to the diagnosis of asthma. A young female
      (with related parents) showed symptoms of cyanosis, dyspnoea and fatigue during
      physical activity despite asthma medication. High levels of methaemoglobin were
      measured. Genetic testing showed homozygote type 1b5r-deficiency. Cyanosis and
      lacking effect of asthma treatment should lead to further diagnostic evaluation
      with arterial blood gas analyses, including assessment of methaemoglobin.
      Congenitally inherited methaemoglobinaemia is a rare disease, but its diagnosis
      is important to ensure correct handling and treatment.

PMID- 21884668
TI  - The impact of an implicit manipulation of self-esteem on body dissatisfaction.
AB  - BACKGROUND AND OBJECTIVES: Given the theoretically postulated causal pathway from
      low self-esteem on body dissatisfaction, the aim of the present study was to
      experimentally test this linkage before and after a mirror exposure in body
      dissatisfied females. METHOD: Thirty-six women with high body dissatisfaction
      (HBD) and 39 women with low body dissatisfaction (LBD) received either a positive
      or a negative implicit manipulation of self-esteem and participants' actual body
      dissatisfaction and negative emotions were assessed (T1). Following that, they
      underwent a one minute mirror exposure and actual body dissatisfaction and
      emotions were assessed once more (T2). RESULTS: In the HBD group no effects of
      the self-esteem manipulation were found prior to the mirror exposure. However,
      the negative manipulation of self-esteem led to a significant increase of body
      dissatisfaction over the course of the mirror exposure. The positive manipulation
      of self-esteem did not decrease body dissatisfaction over the course of the
      mirror exposure. No effects of self-esteem on body dissatisfaction were found in
      the LBD group. LIMITATIONS: Formal eating disorder diagnosis in study
      participants was not established. Therefore, the extension of the results to an
      eating disordered population is recommended. CONCLUSIONS: The results yield
      evidence of a close linkage between negative self-esteem and body dissatisfaction
      in individuals high on body dissatisfaction. Consistent with cognitive theories,
      this link is only apparent when shape and weight schemas are activated, e.g. by
      the confrontation with one's own body.

PMID- 21884670
TI  - Dermatological side effects of hepatitis C and its treatment: patient management
      in the era of direct-acting antivirals.
AB  - Dermatological adverse events (AEs) are an existing concern during hepatitis C
      virus (HCV) infection and peginterferon/ribavirin treatment. HCV infection leads
      to dermatological and muco-cutaneous manifestations including small-vessel
      vasculitis as part of the mixed cryoglobulinemic syndrome.
      Peginterferon/ribavirin treatment is associated with well-characterized
      dermatological AEs tending towards a uniform entity of dermatitis. New direct
      acting antivirals have led to significant improvements in sustained virologic
      response rates, but several have led to an increase in dermatological AEs versus
      peginterferon/ribavirin alone. In telaprevir trials, approximately half of
      treated patients had rash. More than 90% of these events were Grade 1 or 2
      (mild/moderate) and in the majority (92%) of cases, progression to a more severe
      grade did not occur. In a small number of cases (6%), rash led to telaprevir
      discontinuation, whereupon symptoms commonly resolved. Dermatological AEs with
      telaprevir-based triple therapy were generally similar to those observed with
      peginterferon/ribavirin (xerosis, pruritus, and eczema). A few cases were
      classified as severe cutaneous adverse reaction (SCAR), also referred to as
      serious skin reactions, a group of rare conditions that are potentially life
      threatening. It is therefore important to distinguish between telaprevir-related
      dermatitis and SCAR. The telaprevir prescribing information does not require
      telaprevir discontinuation for Grade 1 or 2 (mild/moderate) rash, which can be
      treated using emollients/moisturizers and topical corticosteroids. For Grade 3
      rash, the prescribing information mandates immediate telaprevir discontinuation,
      with ribavirin interruption (with or without peginterferon) within 7 days of
      stopping telaprevir if there is no improvement, or sooner if it worsens. In case
      of suspicion or confirmed diagnosis of SCAR, all study medication must be
      discontinued.

PMID- 21884671
TI  - Acoustic radiation force-based shear stiffness and non-invasive panels of tests
      in Japanese patients with nonalcoholic fatty liver disease.

PMID- 21884672
TI  - Transient elevation of serum bile salts after partial hepatectomy is due to
      metabolic overload and not to cholestasis.

PMID- 21884674
TI  - New observations on the "early repolarization syndrome".

PMID- 21884673
TI  - Profile of L-type Ca(2+) current and Na(+)/Ca(2+) exchange current during cardiac
      action potential in ventricular myocytes.
AB  - OBJECTIVE: The L-type Ca(2+) current (I(Ca,L)) and the Na(+)/Ca(2+) exchange
      current (I(NCX)) are major inward currents that shape the cardiac action
      potential (AP). Previously, the profile of these currents during the AP was
      determined from voltage-clamp experiments that used Ca(2+) buffer. In this study,
      we aimed to obtain direct experimental measurement of these currents during
      cardiac AP with Ca(2+) cycling. METHOD: A newly developed AP-clamp sequential
      dissection method was used to record ionic currents in guinea pig ventricular
      myocytes under a triad of conditions: using the cell's own AP as the voltage
      command, using internal and external solutions that mimic the cell's ionic
      composition, and, importantly, not using any exogenous Ca(2+) buffer. RESULTS:
      The nifedipine-sensitive current (I(NIFE)), which is composed of I(Ca,L) and
      I(NCX), revealed hitherto unreported features during the AP with Ca(2+) cycling
      in the cell. We identified 2 peaks in the current profile followed by a long
      residual current extending beyond the AP, coinciding with a residual
      depolarization. The second peak and the residual current become apparent only
      when Ca(2+) is not buffered. Pharmacological dissection of I(NIFE) by using
      SEA0400 shows that I(Ca,L) is dominant during phases 1 and 2 whereas I(NCX)
      contributes significantly to the inward current during phases 3 and 4 of the AP.
      CONCLUSION: These data provide the first direct experimental visualization of
      I(Ca,L) and I(NCX) during cardiac the AP and Ca(2+) cycle. The residual current
      reported here can serve as a potential substrate for afterdepolarizations when
      increased under pathologic conditions.

PMID- 21884675
TI  - Atrial-selective inhibition of sodium-channel current by Wenxin Keli is effective
      in suppressing atrial fibrillation.
AB  - BACKGROUND: Wenxin Keli is a Chinese herb extract reported to be of benefit in
      the treatment of cardiac arrhythmias, cardiac inflammation, and heart failure.
      METHODS AND RESULTS: We evaluated the electrophysiologic effects of Wenxin Keli
      in isolated canine arterially perfused right atrial preparations with a rim of
      right ventricular tissue (n = 11). Transmembrane action potentials and a
      pseudoelectrocardiogram were simultaneously recorded. Acetylcholine (1 MUM) was
      used to induce atrial fibrillation (AF) and to test the anti-AF potential of
      Wenxin Keli (5 g/L). Wenxin Keli produced preferential abbreviation of action
      potential duration measured at 90% repolarization (APD(90)) in atria, but caused
      atrial-selective prolongation of the effective refractory period, due to the
      development of postrepolarization refractoriness. The maximum rate of rise of the
      action potential upstroke was preferentially reduced in atria. The diastolic
      threshold of excitation increased in both atria and ventricles, but much more in
      atria. The duration of the "P wave" (index of atrial conduction time) was
      prolonged to a much greater extent than the duration of the "QRS complex" (index
      of ventricular conduction time). Wenxin Keli significantly reduced I(Na) and
      shifted steady-state inactivation to more negative potentials in HEK293 cells
      stably expressing SCN5A. Wenxin Keli prevented the induction of persistent AF in
      100% atria (6/6) and, in another experimental series, was found to terminate
      persistent acetylcholine-mediated AF in 100% of atria (3/3). CONCLUSION: Wenxin
      Keli produces atrial-selective depression of I(Na)-dependent parameters in canine
      isolated coronary-perfused preparations via a unique mechanism and is effective
      in suppressing AF and preventing its induction, with minimal effects on the
      ventricular electrophysiology.

PMID- 21884676
TI  - Mouse mammary tumor virus in human breast cancer red herring or smoking gun?

PMID- 21884677
TI  - Voltammetric behavior of complexation of salbutamol with calf thymus DNA and its
      analytical application.
AB  - The interaction of salbutamol (Sal), an animal growth promoter, with DNA was
      investigated by differential pulse voltammetry (DPV), cyclic voltammetry (CV),
      and fluorescence spectroscopy. An irreversible reduction was observed from the
      cyclic voltammograms, and the reaction mechanism involved a one-electron change
      irreversible oxidation. In the presence of DNA, the DPV peak current decreased
      and the Sal peak shifted to higher potentials, indicating that Sal interacted
      with DNA to form an intercalation Sal-DNA complex. In addition, reaction binding
      parameters were extracted from the DPV data with the use of the multivariate
      curve resolution-alternating least squares (MCR-ALS) method; the binding constant
      and ratio were found to be (2.0+/-0.5)*10(5) M(-1) and 1:1, respectively.
      Quantitative voltammetric analysis of Sal was performed in the concentration
      range of 3.02*10(-6) to 1.23*10(-4) molL(-1), and it was found that the detection
      limit was 5.11*10(-7) molL(-1) in the presence of 1.00*10(-6) molL(-1) DNA. The
      method was applied for the determination of Sal in spiked urine and human serum
      samples, and the calibration was successfully verified.

PMID- 21884678
TI  - Transmembrane helices can induce domain formation in crowded model membranes.
AB  - We studied compositionally heterogeneous multi-component model membranes
      comprised of saturated lipids, unsaturated lipids, cholesterol, and alpha-helical
      TM protein models using coarse-grained molecular dynamics simulations. Reducing
      the mismatch between the length of the saturated and unsaturated lipid tails
      reduced the driving force for segregation into liquid-ordered (l(o)) and liquid
      disordered (l(d)) lipid domains. Cholesterol depletion had a similar effect, and
      binary lipid mixtures without cholesterol did not undergo large-scale phase
      separation under the simulation conditions. The phase-separating ternary
      dipalmitoyl-phosphatidylcholine (DPPC)/dilinoleoyl-PC (DLiPC)/cholesterol bilayer
      was found to segregate into l(o) and l(d) domains also in the presence of a high
      concentration of TauMU helices. The l(d) domain was highly crowded with TM
      helices (protein-to-lipid ratio ~1:5), slowing down lateral diffusion by a factor
      of 5-10 as compared to the dilute case, with anomalous (sub)-diffusion on the MUs
      time scale. The membrane with the less strongly unsaturated palmitoyl-linoleoyl
      PC instead of DLiPC, which in the absence of TM alpha-helices less strongly
      deviated from ideal mixing, could be brought closer to a miscibility critical
      point by introducing a high concentration of TM helices. Finally, the 7-TM
      protein bacteriorhodopsin was found to partition into the l(d) domains
      irrespective of hydrophobic matching. These results show that it is possible to
      directly study the lateral reorganization of lipids and proteins in
      compositionally heterogeneous and crowded model biomembranes with coarse-grained
      molecular dynamics simulations, a step toward simulations of realistic,
      compositionally complex cellular membranes. This article is part of a Special
      Issue entitled: Protein Folding in Membranes.

PMID- 21884680
TI  - Protective effect of catechin in type I Gaucher disease cells by reducing
      endoplasmic reticulum stress.
AB  - Gaucher disease (GD) is the most common lysosomal storage disorder (LSD) and is
      divided into three phenotypes, I, II, and III. Type I is the most prevalent form
      and has its onset in adulthood. The degree of endoplasmic reticulum (ER) stress
      is one of the factors that determine GD severity. It has recently been reported
      that antioxidants reduce ER stress and apoptosis by scavenging the oxidants that
      cause oxidative stress. For this report, we investigated the possibility that
      catechin can act on type I GD patient cells to alleviate the pathogenic
      conditions of GD. We treated GD cells with catechin and examined the expression
      level of GRP78/BiP (an ER stress marker) by western blots and fluorescence
      microscopy, the proliferation rate of GD cells, and scratch-induced wound healing
      activity. Our results show that catechin reduces the expression level of
      GRP78/BiP, leads to cell proliferation rates of GD cells similar levels to normal
      cells, and improves wound healing activity. We conclude that catechin protects
      against ER stress in GD cells and catechin-mediated reductions in ER stress may
      be associated with enhanced cell survival.

PMID- 21884681
TI  - Sanguinarine is an allosteric activator of AMP-activated protein kinase.
AB  - We found that a natural product, Sanguinarine, directly interacts with AMPK and
      enhances its enzymatic activity. Cell-based assays confirmed that cellular AMPK
      and the downstream acetyl-CoA carboxylase (ACC) were phosphorylated after
      Sanguinarine treatment. Sanguinarine was shown to exclusively activate AMPK
      holoenzymes containing alpha1gamma1 complexes, and it activated both beta1- and
      beta2-containing isotypes of AMPK. Furthermore, a docking study suggested that
      Sanguinarine binds AMPK at the cleft between the beta and gamma domains whereas
      the physiological activator, AMP, binds at the well-characterized gamma domain
      pocket. In summary, we report that Sanguinarine is a novel, direct activator of
      AMPK that binds by a unique allosteric mechanism different from that of the
      natural AMPK ligand, AMP, and other known AMPK activators. These studies have
      direct applications to the pharmacological study of AMPK activation and the
      potential development of new therapeutics.

PMID- 21884679
TI  - Manipulating the genetic code for membrane protein production: what have we
      learnt so far?
AB  - With synthetic gene services, molecular cloning is as easy as ordering a pizza.
      However choosing the right RNA code for efficient protein production is less
      straightforward, more akin to deciding on the pizza toppings. The possibility to
      choose synonymous codons in the gene sequence has ignited a discussion that dates
      back 50 years: Does synonymous codon use matter? Recent studies indicate that
      replacement of particular codons for synonymous codons can improve expression in
      homologous or heterologous hosts, however it is not always successful.
      Furthermore it is increasingly apparent that membrane protein biogenesis can be
      codon-sensitive. Single synonymous codon substitutions can influence mRNA
      stability, mRNA structure, translational initiation, translational elongation and
      even protein folding. Synonymous codon substitutions therefore need to be
      carefully evaluated when membrane proteins are engineered for higher production
      levels and further studies are needed to fully understand how to select the
      codons that are optimal for higher production. This article is part of a Special
      Issue entitled: Protein Folding in Membranes.

PMID- 21884682
TI  - A coronary artery disease-associated gene product, JCAD/KIAA1462, is a novel
      component of endothelial cell-cell junctions.
AB  - Cell-cell junctions play crucial roles in the organization and function of
      epithelial and endothelial cellular sheets. Here, we have identified the protein
      product for KIAA1462 gene, whose single nucleotide polymorphisms (SNPs) have
      recently reported to be associated with coronary artery disease, as a novel
      component of cell-cell junctions. We propose the name of KIAA1462 protein
      junctional protein associated with coronary artery disease (JCAD). JCAD is a ~145
      kDa protein without any known domains but contains a proline-rich region.
      Immunolocalization studies revealed that JCAD is specifically localized at cell
      cell junctions in endothelial cells but not in epithelial cells. The accumulation
      of JCAD at cell-cell junctions in cultured endothelial cells was impaired by RNAi
      mediated suppression of VE-cadherin expression. In cell adhesion-deficient mouse
      L fibroblasts, JCAD was recruited to cell-cell contacts when cadherin-mediated
      cell-cell adhesion was induced. These results indicate that JCAD is a component
      of VE-cadherin-based cell-cell junctions in endothelial cells. This study also
      suggests the implication of endothelial cell-cell adhesion in coronary artery
      disease.

PMID- 21884683
TI  - RNA polymerase II degradation in response to rapamycin is not mediated through
      ubiquitylation.
AB  - In Saccharomyces cerevisiae, the immunosuppressor rapamycin engenders the
      degradation of excessive RNA polymerase II leading to growth arrest but the
      regulation of this process is not known yet. Here, we show that this mechanism is
      dependent on the peptidyl prolyl cis/trans isomerase Rrd1. Strikingly this
      degradation is independent of RNA polymerase II polyubiquitylation and does not
      require the elongation factor Elc1. Our data reveal that there are at least two
      alternative pathways to degrade RNA polymerase II that depend on different type
      of stresses.

PMID- 21884685
TI  - Interference of deferasirox with assays for serum iron and serum unsaturated iron
      binding capacity during iron chelating therapy.
AB  - BACKGROUND: Deferasirox (DFX) is an oral iron chelator that is used worldwide for
      the treatment of iron overload. Although serum ferritin level is usually measured
      as a marker of the efficacy of DFX, we sometimes experienced unexplainable
      changes in other serum markers for iron. We hypothesized that photometric assays
      for serum iron (sFe) and unsaturated iron binding capacity (UIBC) might be
      affected by DFX. METHODS: Measurement of sFe and UIBC was performed using 4
      different assay systems. The samples were prepared by adding 0-300 MUM DFX to
      pooled human serum or 15 randomized human serum samples. In some experiments, DFX
      iron complex (DFX-Fe) was prepared by mixing iron ammonium citrate solution and
      DFX solution. RESULTS: Measurement of sFe was influenced by DFX-Fe, while iron
      free DFX showed no effect on the value of sFe; DFX-Fe was measured as sFe,
      undistinguishable from transferrin-bound iron. On the other hand, measurement of
      serum UIBC was influenced by DFX itself; DFX might have been bound to iron in the
      reagent used for the assay, leading to an increase in UIBC values. CONCLUSIONS:
      DFX affected the sFe and UIBC assay systems. We must be careful in observing
      these markers during iron chelation therapy with DFX.

PMID- 21884686
TI  - Toll-like receptors and macrophage activation in atherosclerosis.
AB  - Atherosclerosis is a multi-factorial inflammatory disease and is the primary
      initiator of coronary artery and cerebrovascular disease. Initially believed to
      be exclusively lipid-driven, recent evidence demonstrates that inflammation is a
      significant driving force of the disease. Cellular components of innate immunity,
      for example monocytes and macrophages, play a predominant role in
      atherosclerosis. Toll-like receptors (TLRs) are the most characterised innate
      immune receptors and recent evidence demonstrates an important role in
      atherogenesis. Engagement of TLRs results in the transcription of pro
      inflammatory cytokines, foam cell formation and activation of adaptive immunity.
      Recently they have also been implicated in protection from vascular disease. In
      this review, we detail the role of the innate immune system, specifically
      macrophages and TLR signalling, in atherosclerosis and acute cardiovascular
      complications, and thereby identify the potential of TLRs to act as therapeutic
      targets.

PMID- 21884684
TI  - Ethanol impairs muscarinic receptor-induced neuritogenesis in rat hippocampal
      slices: Role of astrocytes and extracellular matrix proteins.
AB  - In an in vitro co-culture system of astrocytes and neurons, stimulation of
      cholinergic muscarinic receptors in astrocytes had been shown to cause
      neuritogenesis in hippocampal neurons, and this effect was inhibited by ethanol.
      The present study sought to confirm these earlier findings in a more complex
      system, in vitro rat hippocampal slices in culture. Exposure of hippocampal
      slices to the cholinergic agonist carbachol (1mM for 24h) induced neurite
      outgrowth in hippocampal pyramidal neurons, which was mediated by activation of
      muscarinic M3 receptors. Specifically, carbachol induced a >4-fold increase in
      the length of the longest neurite, and a 4-fold increase in the length of minor
      neurites and in the number of branches. Co-incubation of carbachol with ethanol
      (50mM) resulted in significant inhibition of the effects induced by carbachol on
      all parameters measured. Neurite outgrowth in CNS neurons is dependent on various
      permissive factors that are produced and released by glial cells. In hippocampal
      slices carbachol increased the levels of two extracellular matrix protein,
      fibronectin and laminin-1, by 1.6-fold, as measured by Western blot. Co
      incubation of carbachol with ethanol significantly inhibited these increases.
      Carbachol-induced increases in levels of extracellular matrix proteins were
      antagonized by a M3 muscarinic receptor antagonist. Furthermore, function
      blocking fibronectin or laminin-1 antibodies antagonized the effect of carbachol
      on neurite outgrowth. These results indicate that in hippocampal slices
      stimulation of muscarinic M3 receptors induces neurite outgrowth, which is
      mediated by fibronectin and laminin-1, two extracellular matrix proteins released
      by astrocytes. By decreasing fibronectin and laminin levels ethanol prevents
      carbachol-induced neuritogenesis. These findings highlight the importance of
      glial-neuronal interactions as important targets in the developmental
      neurotoxicity of alcohol.

PMID- 21884687
TI  - Rapid allele-specific PCR method for CDA 79A>C (K27Q) genotyping: a useful
      pharmacogenetic tool and world-wide polymorphism distribution.
AB  - BACKGROUND: The CDA 79A>C (K27Q, rs2072671) functional SNP has recently shown a
      crucial role in the pharmacogenetics of cytidine-based anticancer drugs widely
      administered to different subsets of patients. Current gold standard in screening
      for the CDA rs2072671 is the sequence-based genotyping method. Here we developed
      a novel, rapid Allele-Specific PCR method for CDA rs2072671 genotyping. METHODS:
      DNA was extracted from 324 healthy individuals from two different populations
      (Italian and Han Chinese). CDA rs2072671 genotyping was performed by Allele
      Specific PCR. Sequencing was performed to validate the test results. Results
      obtained from population screening were compared to that already available in
      HapMap and in the literature. RESULTS: Samples analyzed were successfully
      genotyped and the results were confirmed by sequencing. Genotype distribution
      does not differ significantly from that previously reported for each relative
      ethnic group. Also, the world-wide distribution of the CDA rs2072671 SNP is
      reported. A striking difference is present among the main ethnicities
      (p=1.715*10(-77)), with CDA*27Q allele showing the lowest frequency in African
      group (9.7%) and the highest in Caucasians (35.9%). CONCLUSION: This Allele
      Specific PCR method is a useful tool in pharmacogenetics research and a valid and
      reliable alternative for CDA rs2072671 screening where sequencing or Real-Time
      PCR is not available.

PMID- 21884688
TI  - Assessment of two thawing processes of cryopreserved human sperm in pellets.
AB  - In this study, we evaluated the effects of the thawing methodology on sperm
      function after cryopreservation in pellets. We compared the use of two thawing
      procedures: method (1) maintaining pellet for 10 min in air at room temperature,
      then another 10-min period in air at 37 degrees C followed by dilution in a
      thawing medium; and method (2) immersing the pellets directly in thawing medium
      at 37 degrees C for 20 min. This procedure leads to a higher rate of temperature
      increase and a dilution of the glycerol present in the freezing medium. We
      analyzed the effect of the thawing procedure on sperm motility, viability,
      membrane lipid packing disorder, acrosome status, reactive oxygen species (ROS)
      level and sperm chromatin condensation. This study revealed a positive effect of
      the M2 thawing methodology on sperm parameters. The percentage of spermatozoa
      with fast-linear movement is increased (M1: 17.26% vs. M2: 28.05%, p<0.01), with
      higher viability (M1: 37.81% vs. M2: 40.15%, p<0.01) and less acrosome damage
      (M1: 40.44% vs. M2: 35.45%, p=0.02). We also detected an increase in the
      percentage of viable spermatozoa with low membrane lipid disorder (M1: 31.36% vs.
      M2: 33.17%, p=0.03) and a reduction in chromatin condensation (44.62 vs. 46.62
      arbitrary units, p=0.02). Further studies will be necessary to evaluate the
      possible clinical applications.

PMID- 21884689
TI  - Effects of cooling rate, annealing time and biological antifreeze concentration
      on thermal hysteresis reading.
AB  - Thermal hysteresis (TH) readings depend on the cooling rate, annealing time and
      the concentration of the biological antifreeze (AF) (i.e., antifreeze protein or
      antifreeze glycoprotein). Such time- and concentration-dependent TH readings are
      not true (or absolute) values. The true TH should be independent of time and AF
      concentration, and it should be a unique value for a given AF. Only the true TH
      can be used to assess the activity of an AF. A mathematical model is proposed to
      explain the time- and concentration-dependent behavior of AFs. The model assumes
      a reversible Langmuir adsorption mechanism for the AF molecules and the Kelvin
      effect to be applicable. A TH equation that correlates the TH reading with the
      cooling rate, annealing time and AF concentration was derived. The time-dependent
      behavior was attributed to the slow adsorption process of the AF. The theoretical
      calculations were compared with previously published data on the effects of the
      cooling rate, annealing time and AF concentration on TH readings. The calculated
      results agree qualitatively with the literature data. The experimental
      methodology required for obtaining the true TH of an AF is suggested.

PMID- 21884690
TI  - The effects of preservation procedures on amniotic membrane's ability to serve as
      a substrate for cultivation of endothelial cells.
AB  - Amniotic membrane (AM) has been used as a scaffold for the ex vivo expansion of
      different types of cells and a cell delivery matrix in regenerative medicine.
      Since the preservation procedures can influence the AM properties for
      experimental and clinical purposes, this study was established to investigate the
      feasibility of using the AM after different preservation methods to serve as
      substrates for endothelial cell expansion ex vivo. The effects of
      cryopreservation and lyophilization were evaluated on mechanical and histological
      characteristics of the AM, and the results were compared with the fresh AM. The
      ECM components of the basement membrane were well conserved in all groups.
      Although lyophilization resulted in more histological changes and lower level of
      physical variables including thickness, F(max), elongation at break and suture
      retention than the fresh and cryopreserved AM, endothelial cells grown on the
      lyophilized AM were better attached to the basement membrane. Cytotoxicity assay
      by MTT showed that the lyophilized AM is a compatible substrate for endothelial
      cells cultivation. The findings of this study suggest that the lyophilized AM is
      a suitable matrix for cultivation of endothelial cells due to this fact that
      lyophilization led to exposure of basement membrane of the AM.

PMID- 21884691
TI  - Heterologous expression, refolding and functional characterization of two
      antifreeze proteins from Fragilariopsis cylindrus (Bacillariophyceae).
AB  - Antifreeze proteins (AFPs) provide protection for organisms subjected to the
      presence of ice crystals. The psychrophilic diatom Fragilariopsis cylindrus which
      is frequently found in polar sea ice carries a multitude of AFP isoforms. In this
      study we report the heterologous expression of two antifreeze protein isoforms
      from F. cylindrus in Escherichia coli. Refolding from inclusion bodies produced
      proteins functionally active with respect to crystal deformation,
      recrystallization inhibition and thermal hysteresis. We observed a reduction of
      activity in the presence of the pelB leader peptide in comparison with the GS
      linked SUMO-tag. Activity was positively correlated to protein concentration and
      buffer salinity. Thermal hysteresis and crystal deformation habit suggest the
      affiliation of the proteins to the hyperactive group of AFPs. One isoform,
      carrying a signal peptide for secretion, produced a thermal hysteresis up to 1.53
      degrees C+/-0.53 degrees C and ice crystals of hexagonal bipyramidal shape. The
      second isoform, which has a long preceding N-terminal sequence of unknown
      function, produced thermal hysteresis of up to 2.34 degrees C+/-0.25 degrees C.
      Ice crystals grew in form of a hexagonal column in presence of this protein. The
      different sequences preceding the ice binding domain point to distinct
      localizations of the proteins inside or outside the cell. We thus propose that
      AFPs have different functions in vivo, also reflected in their specific TH
      capability.

PMID- 21884692
TI  - Genesis of muscle fiber-type diversity during mouse embryogenesis relies on Six1
      and Six4 gene expression.
AB  - Adult skeletal muscles in vertebrates are composed of different types of
      myofibers endowed with distinct metabolic and contraction speed properties.
      Genesis of this fiber-type heterogeneity during development remains poorly known,
      at least in mammals. Six1 and Six4 homeoproteins of the Six/sine oculis family
      are expressed throughout muscle development in mice, and Six1 protein is enriched
      in the nuclei of adult fast-twitch myofibers. Furthermore, Six1/Six4 proteins are
      known to control the early activation of fast-type muscle genes in myocytes
      present in the mouse somitic myotome. Using double Six1:Six4 mutants (SixdKO) to
      dissect in vivo the genesis of muscle fiber-type heterogeneity, we analyzed here
      the phenotype of the dorsal/epaxial muscles remaining in SixdKO. We show by
      electron microscopy analysis that the absence of these homeoproteins precludes
      normal sarcomeric organization of the myofiber leading to a dystrophic aspect,
      and by immunohistochemistry experiments a deficiency in synaptogenesis.
      Affymetrix transcriptome analysis of the muscles remaining in E18.5 SixdKO
      identifies a major role for these homeoproteins in the control of genes that are
      specifically activated in the adult fast/glycolytic myofibers, particularly those
      controlling Ca(2+) homeostasis. Absence of Six1 and Six4 leads to the development
      of dorsal myofibers lacking expression of fast-type muscle genes, and mainly
      expressing a slow-type muscle program. The absence of restriction of the slow
      type program during the fetal period in SixdKO back muscles is associated with a
      decreased HDAC4 protein level, and subcellular relocalization of the
      transcription repressor Sox6. Six genes thus behave as essential global
      regulators of muscle gene expression, as well as a central switch to drive the
      skeletal muscle fast phenotype during fetal development.

PMID- 21884694
TI  - CYFIP dependent actin remodeling controls specific aspects of Drosophila eye
      morphogenesis.
AB  - Cell rearrangements shape organs and organisms using molecular pathways and
      cellular processes that are still poorly understood. Here we investigate the role
      of the Actin cytoskeleton in the formation of the Drosophila compound eye, which
      requires extensive remodeling and coordination between different cell types. We
      show that CYFIP/Sra-1, a member of the WAVE/SCAR complex and regulator of Actin
      remodeling, controls specific aspects of eye architecture: rhabdomere extension,
      rhabdomere terminal web organization, adherens junctions, retina depth and
      basement membrane integrity. We demonstrate that some phenotypes manifest
      independently, due to defects in different cell types. Mutations in WAVE/SCAR and
      in ARP2/3 complex subunits but not in WASP, another major regulator of Actin
      nucleation, phenocopy CYFIP defects. Thus, the CYFIP-SCAR-ARP2/3 pathway
      orchestrates specific tissue remodeling processes.

PMID- 21884693
TI  - Myo/Nog cell regulation of bone morphogenetic protein signaling in the blastocyst
      is essential for normal morphogenesis and striated muscle lineage specification.
AB  - Cells that express MyoD mRNA, the G8 antigen and the bone morphogenetic protein
      (BMP) inhibitor noggin (Nog) are present in the epiblast before gastrulation.
      Ablation of "Myo/Nog" cells in the blastocyst results in an expansion of
      canonical BMP signaling and prevents the expression of noggin and follistatin
      before and after the onset of gastrulation. Once eliminated in the epiblast, they
      are neither replaced nor compensated for as development progresses. Older embryos
      lacking Myo/Nog cells exhibit severe axial malformations. Although Wnts and Sonic
      hedgehog are expressed in ablated embryos, skeletal muscle progenitors expressing
      Pax3 are missing in the somites. Pax3+ cells do emerge adjacent to Wnt3a+ cells
      in vitro; however, few undergo skeletal myogenesis. Ablation of Myo/Nog cells
      also results in ectopically placed cardiac progenitors and cardiomyocytes in the
      somites. Reintroduction of Myo/Nog cells into the epiblast of ablated embryos
      restores normal patterns of BMP signaling, morphogenesis and skeletal myogenesis,
      and inhibits the expression of cardiac markers in the somites. This study
      demonstrates that Myo/Nog cells are essential regulators of BMP signaling in the
      early epiblast and are indispensable for normal morphogenesis and striated muscle
      lineage specification.

PMID- 21884695
TI  - Quantitative analysis of multiple methylated genes in plasma for the diagnosis
      and prognosis of hepatocellular carcinoma.
AB  - This study was aimed to evaluate the clinical value of plasma methylation
      analysis of a panel of four genes (APC, GSTP1, RASSF1A, and SFRP1), which was
      identified by our previous work, for the noninvasive diagnosis of hepatocellular
      carcinoma (HCC). The methylation status of these four genes in 150 plasma samples
      from 72 patients with HCC, 37 benign live diseases and 41 normal controls was
      detected with methylation-sensitive restriction enzymes-based quantitative PCR
      (MSRE-qPCR) method. The plasma methylation levels of APC, GSTP1, RASSF1A, and
      SFRP1 were significantly higher in HCCs than those in normal or benign controls
      (P<0.05). Although the area under the receiver-operation characteristic curve
      (AUC-ROC) for individual gene was moderate (range, from 0.800 to 0.881), the
      combination analysis of these four genes resulted in an increased AUC of 0.933
      with 92.7% sensitivity, 81.9% specificity, 90.5% positive predictive value (PPV),
      and 87.2% negative predictive value (NPV) in discriminating HCC from normal
      control. The combination analysis also indicated an increased AUC of 0.877 when
      compared with individual gene (from 0.666 to 0.850) in discriminating HCC from
      benign control, and the consultant sensitivity, specificity, PPV, and NPV was
      84.7%, 81.1%, 89.7%, and 73.2%, respectively. Patients with elevated plasma
      methylation levels of APC or RASSF1A showed poorer overall survival than those
      with low levels (P<0.05). Cox multivariate analysis demonstrated methylated
      RASSF1A in plasma to be an independent prognostic factor for overall survival
      (hazard ratio=3.262, 95% CI: 1.476-7.209, P=0.003). These data showed that
      quantitative analysis of multiple methylated genes in plasma may be a promising
      tool for noninvasive diagnosis of HCC; and methylated plasma RASSF1A appears to
      be a prognostic marker of HCC.

PMID- 21884696
TI  - Wnt signaling and colon tumorigenesis--a view from the periphery.
AB  - In this brief overview we discuss the association between Wnt signaling and colon
      cell biology and tumorigenesis. Our current understanding of the role of Apc in
      the beta-catenin destruction complex is compared with potential roles for Apc in
      cell adhesion and migration. The requirement for phosphorylation in the
      proteasomal-mediated degradation of beta-catenin is contrasted with roles for
      phospho-beta-catenin in the activation of transcription, cell adhesion and
      migration. The synergy between Myb and beta-catenin regulation of transcription
      in crypt stem cells during Wnt signaling is discussed. Finally, potential effects
      of growth factor regulatory systems, Apc or truncated-Apc on crypt morphogenesis,
      stem cell localization and crypt fission are considered.

PMID- 21884697
TI  - A micro-advancer device for vitreal injection and retinal recording and
      stimulation.
AB  - A micro-advancer device that positions a narrow-gauge needle within the vitreous
      humor of the rat eye is described. The device is compact, simple and inexpensive
      to manufacture. It consists of an outer guard needle and an inner injection
      needle that is advanced through the guard needle. With the rat held in a
      stereotaxic holder and the globe fixed to a stabilizing ring, the outer 25-gauge
      guard needle is advanced through the sclera using a standard micromanipulator.
      The inner 31-gauge injection needle is then advanced through the guard needle
      with a manually controlled leadscrew and carriage mechanism. The inner injection
      needle is attached to a Hamilton syringe and can be positioned to within microns
      of the retinal surface under visual observation through a microscope. The
      injection needle is fixed to the device by a quick-release clamp on the carriage
      and can be rapidly exchanged while the guard needle remains in place in the
      vitreous. This permits different solutions to be injected sequentially into the
      vitreous humor. Recording electrodes, stimulating electrodes, and optical fibers
      can also be advanced through the guard needle and positioned accurately near the
      retinal surface or within the retina.

PMID- 21884698
TI  - Cortical and subcortical compensatory mechanisms after spinal cord injury in
      monkeys.
AB  - This is a review of our investigations into the neuronal mechanisms of functional
      recovery after spinal cord injury (SCI) in a non-human primate model. In
      primates, the lateral corticospinal tract (l-CST) makes monosynaptic connections
      with spinal motoneurons. The existence of direct cortico-motoneuronal (CM)
      connections has been thought to be the basis of dexterous digit movements, such
      as precision gripping. However, recent studies have shown that after lesion of
      the direct CM connections, by a l-CST lesion at the C4/C5 level, precision
      gripping is initially impaired, but shows remarkable recovery with training
      within several weeks. Plastic changes of the neural circuits underlying the
      recovery occur at various levels of the central nervous system. In the
      subcortical networks, intracellular recordings from the motoneurons in
      anesthetized animals demonstrated that transmission through the disynaptic
      pathways from the CST was enhanced, presumably mediated by the propriospinal
      neurons in the mid-cervical segments. The gamma-band musculo-muscular coherence
      (MMC), with a peak frequency around 30 Hz, appeared over a wide range of forelimb
      muscles and was strengthened in parallel to the recovery of the precision grip.
      Appearance of the gamma-band MMC also paralleled the change in the activation
      pattern of forelimb muscles; muscles which were antagonists before the lesion
      showed co-activation after recovery. Such gamma-band MMC is thought to originate
      in the subcortical network, presumably in the brainstem or spinal cord. In the
      cortical networks, a combination of positron emission tomography and reversible
      inactivation techniques has shown that the bilateral primary motor cortex (M1)
      and ventral premotor cortex (PMv) have different contributions to functional
      recovery depending on the recovery stage; the bilateral M1 plays a major role in
      early stage recovery (<1 month), whereas the contralateral M1 and bilateral PMv
      are the prominent contributors to the later stages (3-4 months). Such changes in
      cortical activity in M1 and PMv have been shown to accompany changes in the
      expressions of plasticity-related genes, such as GAP-43. Changes in the dynamic
      properties of neural circuits, both at the cortical and subcortical levels, are
      time-dependent. Multidisciplinary studies to clarify how the changes in the
      dynamic properties of individual components of the large-scaled networks are
      coordinated during recovery will help to develop effective therapeutic strategies
      to recovery from SCI.

PMID- 21884699
TI  - High-mobility group box-1 impairs memory in mice through both toll-like receptor
      4 and Receptor for Advanced Glycation End Products.
AB  - High-mobility group box-1 (HMGB1) is a nuclear protein with cytokine-type
      functions upon its extracellular release. HMGB1 activates inflammatory pathways
      by stimulating multiple receptors, chiefly toll-like receptor 4 (TLR4) and
      Receptor for Advanced Glycation End Products (RAGE). TLR4 and RAGE activation has
      been implicated in memory impairments, although the endogenous ligand subserving
      these effects is unknown. We examined whether HMGB1 induced memory deficits using
      novel object recognition test, and which of the two receptor pathways was
      involved in these effects. Non-spatial long-term memory was examined in wild
      type, TLR4 knockout, and RAGE knockout mice. Recombinant HMGB1 (10MUg,
      intracerebroventricularly, i.c.v.) disrupted memory encoding equipotently in wild
      type, TLR4 knockout and RAGE knockout animals, but affected neither memory
      consolidation, nor retrieval. Neither TLR4 knockout nor RAGE knockout mice per
      se, exhibited memory deficits. Blockade of TLR4 in RAGE knockout mice using
      Rhodobacter sphaeroides lipopolysaccharide (LPS-Rs; 20 MUg, i.c.v.) prevented the
      detrimental effect of HMGB1 on memory. These data show that elevated brain levels
      of HMGB1 induce memory abnormalities which may be mediated by either TLR4, or
      RAGE. This mechanism may contribute to memory deficits under various neurological
      and psychiatric conditions associated with the increased HMGB1 levels, such as
      epilepsy, Alzheimer's disease and stroke.

PMID- 21884700
TI  - Cystic retroperitoneal swelling occupying the whole abdomen. Diagnosis:
      Schwannoma.

PMID- 21884701
TI  - MMPs 2 and 9 are essential for coronary collateral growth and are prominently
      regulated by p38 MAPK.
AB  - Transient, repetitive ischemia (RI) stimulates coronary collateral growth (CCG)
      in normal, healthy (SD) rats, which requires p38 MAPK activation. In contrast, RI
      does not induce CCG in the metabolic syndrome (JCR) rats, which is associated
      with lack of p38 MAPK activation. The functional consequences of p38 MAPK
      activation in CCG remain unknown. Theoretically, effective collateral growth
      would require extracellular matrix remodeling; however, direct assessment as well
      as identification of proteases responsible for this degradation are lacking. In
      this study, we investigated the role of p38 MAPK in the regulation of matrix
      metalloproteinases 2 and 9 (MMPs 2 and 9) and their requirement for CCG in SD vs.
      JCR rats. The rats underwent the RI protocol (8 LAD occlusions, 40s each, every
      20min, in 8h cycles for 0, 3, 6, or 9days). MMP expression was measured in the
      ischemic, collateral-dependent zone (CZ) and the normal zone (NZ) by Western
      blot, and MMP activity by zymography. Expression and activation of MMP 2 and 9
      were significantly increased (~3.5 fold) on day 3 of RI in the CZ of SD rats. In
      vivo p38 MAPK inhibition completely blocked RI-induced MMP 2 and 9 expression and
      activation. MMP activation correlated with increased degradation of components of
      the basement membrane and the vascular elastic laminae: elastin (~3 fold),
      laminin (~3 fold) and type IV collagen (~2 fold). This was blocked by MMP 2 and 9
      inhibition, which also abolished RI-induced CCG. In contrast, in JCR rats, RI did
      not induce expression or activation of MMP 2 or 9 and there was no associated
      degradation of elastin, laminin or type IV collagen. In conclusion, MMP 2 and 9
      activation is essential for CCG and is mediated, in part, by p38 MAPK.
      Furthermore, compromised CCG in the metabolic syndrome may be partially due to
      the lack of p38 MAPK-dependent activation of MMP 2 and 9 and resultant decreased
      extracellular matrix degradation.

PMID- 21884702
TI  - Syntaxin-1A inhibits KATP channels by interacting with specific conserved motifs
      within sulfonylurea receptor 2A.
AB  - We previously demonstrated that syntaxin (Syn)-1A is present in the sarcolemma of
      rat cardiomyocytes and binds sulfonylurea receptor (SUR) 2A nucleotide binding
      folds (NBFs) to inhibit ATP-sensitive potassium (K(ATP)) channel. Here, we
      examined for the precise domains within the NBFs of SUR2A that may interact with
      Syn-1A. Specifically, we tested truncated NBF protein segments encompassing the
      conserved motifs Walker A (W(A)), signature/Linker (L), and Walker B (W(B)). In
      vitro binding results indicate that the domains encompassing W(A) and L of NBF-1
      and all three conserved motifs of NBF-2 bound Syn-1A. Electrophysiological
      studies, employing inside-out patch-clamp recordings from SUR2A/Kir6.2 expressing
      HEK cells and mouse cardiomyocytes, show that W(B) and L of NBF-1 and all three
      NBF-2 truncated protein segments reduced Syn-1A inhibition of SUR2A/K(ATP)
      channels. Remarkably, these same NBF-1 and -2 truncated proteins could
      independently disrupt the intimate FRET interactions of full length SUR2A (
      mCherry) and Syn-1A (-EGFP). These results taken together indicate that Syn-1A
      possibly maintains inhibition of cardiac ventricular K(ATP) channels by binding
      to large regions of NBF-1 and NBF-2 to stabilize the NBF-1-NBF-2 heterodimer
      formation and prevent ATP-binding and ATP hydrolysis. Since K(ATP) channels are
      closely coupled to metabolic states, we postulate that these very intimate Syn-1A
      SUR2A interactions are critically important for myocardial protection during
      stress, in which profound changes in metabolic factors (pH, ATP) could modulate
      these Syn-1A-SUR2A interactions.

PMID- 21884703
TI  - Atheroprotection via cannabinoid receptor-2 is mediated by circulating and
      vascular cells in vivo.
AB  - Low-dose oral tetrahydrocannabinol (THC) reduces progression of atherosclerosis
      in mice. THC activates central cannabinoid-1 receptors (CB1) with subsequent
      psychoactive effects as well as peripheral cannabinoid-2 receptors (CB2). In
      order to dissect the underlying mechanisms, we performed experiments under
      selective CB2 stimulation as well as after genetic disruption of the CB2
      receptor. Atherosclerosis prone apolipoprotein E-deficient mice were crossed with
      cannabinoid receptor-2 deficient mice to obtain ApoE -/- CB2 -/- double knockout
      mice. After 8weeks of a high-cholesterol diet, immunohistochemical stainings of
      the aortic root revealed that vascular leukocyte infiltration in atherosclerotic
      plaques was accelerated in ApoE -/- CB2 -/- mice compared with ApoE -/- mice.
      This was accompanied by increased release of reactive oxygen species as measured
      using L012-enhanced chemiluminescence, and by decreased endothelial function as
      assessed in isolated aortic rings in organ chamber experiments. ApoE -/- mice
      treated with the selective CB2 agonist JWH 133 during a high-cholesterol diet
      showed decreased atherosclerotic lesion formation, improved endothelial function
      and reduced levels of reactive oxygen species. To assess whether CB2 expression
      in circulating cells influences atherosclerosis, irradiated ApoE -/- mice were
      repopulated with bone marrow-derived cells from ApoE -/- and ApoE -/- CB2 -/-
      mice and were fed a high-cholesterol diet for 8weeks. CB2 deficiency in bone
      marrow-derived cells increased leukocyte infiltration into the vessel wall, but
      had no impact on plaque formation. Cell culture experiments revealed that CB2
      activation diminishes ROS generation in vascular cells. Selective CB2 receptor
      stimulation modulates atherogenesis via impact on both circulating
      proinflammatory and vascular cells.

PMID- 21884705
TI  - Archaeal translation initiation factor aIF2 can substitute for eukaryotic eIF2 in
      ribosomal scanning during mammalian 48S complex formation.
AB  - Heterotrimeric translation initiation factor (IF) a/eIF2 (archaeal/eukaryotic IF
      2) is present in both Eukarya and Archaea. Despite strong structural similarity
      between a/eIF2 orthologs from the two domains of life, their functional
      relationship is obscure. Here, we show that aIF2 from Sulfolobus solfataricus can
      substitute for its mammalian counterpart in the reconstitution of eukaryotic 48S
      initiation complexes from purified components. aIF2 is able to correctly place
      the initiator Met-tRNA(i) into the P-site of the 40S ribosomal subunit and
      accompany the entire set of eukaryotic translation IFs in the process of cap
      dependent scanning and AUG codon selection. However, it seems to be unable to
      participate in the following step of ribosomal subunit joining. In accordance
      with this, aIF2 inhibits rather than stimulates protein synthesis in mammalian
      cell-free system. The ability of recombinant aIF2 protein to direct ribosomal
      scanning suggests that some archaeal mRNAs may utilize this mechanism during
      translation initiation.

PMID- 21884704
TI  - A new structural form in the SAM/metal-dependent o-methyltransferase family: MycE
      from the mycinamicin biosynthetic pathway.
AB  - O-linked methylation of sugar substituents is a common modification in the
      biosynthesis of many natural products and is catalyzed by multiple families of S
      adenosyl-L-methionine (SAM or AdoMet)-dependent methyltransferases (MTs).
      Mycinamicins, potent antibiotics from Micromonospora griseorubida, can be
      methylated at two positions on a 6-deoxyallose substituent. The first methylation
      is catalyzed by MycE, a SAM- and metal-dependent MT. Crystal structures were
      determined for MycE bound to the product S-adenosyl-L-homocysteine (AdoHcy) and
      magnesium, both with and without the natural substrate mycinamicin VI. This
      represents the first structure of a natural product sugar MT in complex with its
      natural substrate. MycE is a tetramer of a two-domain polypeptide, comprising a C
      terminal catalytic MT domain and an N-terminal auxiliary domain, which is
      important for quaternary assembly and for substrate binding. The symmetric MycE
      tetramer has a novel MT organization in which each of the four active sites is
      formed at the junction of three monomers within the tetramer. The active-site
      structure supports a mechanism in which a conserved histidine acts as a general
      base, and the metal ion helps to position the methyl acceptor and to stabilize a
      hydroxylate intermediate. A conserved tyrosine is suggested to support activity
      through interactions with the transferred methyl group from the SAM methyl donor.
      The structure of the free enzyme reveals a dramatic order-disorder transition in
      the active site relative to the S-adenosyl-L-homocysteine complexes, suggesting a
      mechanism for product/substrate exchange through concerted movement of five loops
      and the polypeptide C-terminus.

PMID- 21884706
TI  - Analyses of the functional regions of DEAD-box RNA "helicases" with deletion and
      chimera constructs tested in vivo and in vitro.
AB  - The DEAD-box family of putative RNA helicases is composed of ubiquitous proteins
      that are found in nearly all organisms and that are involved in virtually all
      processes involving RNA. They are characterized by two tandemly linked, RecA-like
      domains that contain 11 conserved motifs and highly variable amino- and carboxy
      terminal flanking sequences. For this reason, they are often considered to be
      modular multi-domain proteins. We tested this by making extensive BLASTs and
      sequence alignments to elucidate the minimal functional unit in nature. We then
      used this information to construct chimeras and deletions of six essential yeast
      proteins that were assayed in vivo. We purified many of the different constructs
      and characterized their biochemical properties in vitro. We found that sequence
      elements can only be switched between closely related proteins and that the
      carboxy-terminal sequences are important for high ATPase and strand displacement
      activities and for high RNA binding affinity. The amino-terminal elements were
      often toxic when overexpressed in vivo, and they may play regulatory roles. Both
      the amino and the carboxyl regions have a high frequency of sequences that are
      predicted to be intrinsically disordered, indicating that the flanking regions do
      not form distinct modular domains but probably assume an ordered structure with
      ligand binding. Finally, the minimal functional unit of the DEAD-box core starts
      two amino acids before the isolated phenylalanine of the Q motif and extends to
      about 35 residues beyond motif VI. These experiments provide evidence for how a
      highly conserved structural domain can be adapted to different cellular needs.

PMID- 21884707
TI  - Deformation and reperfusion damages and their accumulation in subcutaneous
      tissues during loading and unloading: a theoretical modeling of deep tissue
      injuries.
AB  - Deep tissue injuries (DTI) involve damages in the subcutaneous tissues under
      intact skin incurred by prolonged excessive epidermal loadings. This paper
      presents a new theoretical model for the development of DTI, broadly based on the
      experimental evidence in the literatures. The model covers the loading damages
      implicitly inclusive of both the direct mechanical and ischemic injuries, and the
      additional reperfusion damages and the competing healing processes during the
      unloading phase. Given the damage accumulated at the end of the loading period,
      the relative strength of the reperfusion and the healing capacity of the involved
      tissues system, the model provides a description of the subsequent damage
      evolution during unloading. The model is used to study parametrically the
      scenario when reperfusion damage dominates over healing upon unloading and the
      opposite scenario when the loading and subsequent reperfusion damages remain
      small relative to the healing capacity of the tissues system. The theoretical
      model provides an integrated understanding of how tissue damage may further build
      up paradoxically even with unloading, how long it would take for the loading and
      reperfusion damages in the tissues to become fully recovered, and how such
      loading and reperfusion damages, if not given sufficient time for recovery, may
      accumulate over multiple loading and unloading cycles, leading to clinical deep
      tissues ulceration.

PMID- 21884708
TI  - Synaptic glutamate spillover increases NMDA receptor reliability at the
      cerebellar glomerulus.
AB  - Glutamate spillover in the mossy fiber to granule cell cerebellar glomeruli has
      been hypothesized to increase neurotransmission reliability. In this study, we
      evaluate this hypothesis using an experimentally based quantitative model of
      glutamate spillover on the N-methyl-d-aspartate receptors (NMDA-Rs) at the
      cerebellar glomerulus. The transient and steady-state responses of NMDA-Rs were
      examined over a physiological range of firing rates. Examined cases included
      direct glutamate release activation, glutamate spillover activation, and a
      combination of direct and spillover activation. Our results illustrate that the
      effects of spillover alone are equivalent to direct release and, notably,
      combined spillover and direct release effects on NMDA-Rs are not additive. Our
      results show that spillover does in fact provide a high degree of reliability
      given that the synaptic vesicle release rate must fall to approximately 15-25% of
      what is considered the normal baseline level in order to substantially alter
      neurotransmission across the examined range of frequencies. We suggest that the
      high reliability provided by activation due to glutamate spillover could be used
      to conserve energy by reducing the required overall glutamate load at higher
      frequencies.

PMID- 21884709
TI  - In vitro transcriptomic prediction of hepatotoxicity for early drug discovery.
AB  - Liver toxicity (hepatotoxicity) is a critical issue in drug discovery and
      development. Standard preclinical evaluation of drug hepatotoxicity is generally
      performed using in vivo animal systems. However, only a small number of
      preselected compounds can be examined in vivo due to high experimental costs. A
      more efficient yet accurate screening technique that can identify potentially
      hepatotoxic compounds in the early stages of drug development would thus be
      valuable. Here, we develop and apply a novel genomic prediction technique for
      screening hepatotoxic compounds based on in vitro human liver cell tests. Using a
      training set of in vivo rodent experiments for drug hepatotoxicity evaluation, we
      discovered common biomarkers of drug-induced liver toxicity among six
      heterogeneous compounds. This gene set was further triaged to a subset of 32
      genes that can be used as a multi-gene expression signature to predict
      hepatotoxicity. This multi-gene predictor was independently validated and showed
      consistently high prediction performance on five test sets of in vitro human
      liver cell and in vivo animal toxicity experiments. The predictor also
      demonstrated utility in evaluating different degrees of toxicity in response to
      drug concentrations, which may be useful not only for discerning a compound's
      general hepatotoxicity but also for determining its toxic concentration.

PMID- 21884710
TI  - Behavioral sexual dimorphism in models of anxiety and depression due to changes
      in HPA axis activity.
AB  - Anxiety and depression are considered as stress-related disorders, which present
      considerable sex differentiation. In animal models of anxiety and depression sex
      differences have been described and linked to the sexually dimorphic hypothalamus
      pituitary-adrenals (HPA) axis. The present study aimed to adjust corticosterone,
      the main HPA axis stress hormone, in male and female adrenalectomized rats with
      oral (25 MUg/ml) corticosterone replacement (ADXR). Subsequently we investigated
      the behavioral performance of ADXR rats in the open field, light/dark and forced
      swim test (FST). Male ADXR rats showed less anxiety-like behavior when compared
      to sham-operated controls, despite adequate corticosterone replacement. They
      further showed increased swimming and reduced climbing behavior in the FST, while
      immobility duration did not differ from sham-operated males. On the contrary,
      adrenalectomy and corticosterone replacement did not have significant effects on
      the female behavioral response. Females were generally more active and presented
      less anxiety-like behavior than males, while they exhibited higher depressive
      like symptomatology in the FST. ADXR affected behavioral responses predominantly
      in males, which in turn modified sex differences in the behavioral profile.
      Females in proestrous and estrous did not differ from females in diestrous and
      methestrous in any measured behavioral response. Present results suggest that the
      male and not the female behavioral responses in models of anxiety and depression
      were mainly affected by ADXR. These findings may play a significant role in
      explaining the differential coping strategy of the two sexes in response to
      stressful experiences. This article is part of a Special Issue entitled 'Anxiety
      and Depression'.

PMID- 21884711
TI  - On the role of brain 5-HT7 receptor in the mechanism of hypothermia: comparison
      with hypothermia mediated via 5-HT1A and 5-HT3 receptor.
AB  - Intracerebroventricular administration of selective agonist of serotonin 5-HT(7)
      receptor LP44 (4-[2-(methylthio)phenyl]-N-(1,2,3,4-tetrahydro-1-naphthalenyl)-1
      pyperasinehexanamide hydrochloride; 10.3, 20.5 or 41.0 nmol) produced
      considerable hypothermic response in CBA/Lac mice. LP44-induced (20.5 nmol)
      hypothermia was significantly attenuated by the selective 5-HT(7) receptor
      antagonist SB 269970 (16.1 fmol, i.c.v.) pretreatment. At the same time,
      intraperitoneal administration of LP44 in a wide range of doses 1.0, 2.0 or 10.0
      mg/kg (2.0, 4.0, 20.0 MUmol/kg) did not cause considerable hypothermic response.
      These findings indicate the implication of central, rather than peripheral 5
      HT(7) receptors in the regulation of hypothermia. The comparison of LP44-induced
      (20.5 nmol) hypothermic reaction in eight inbred mouse strains (DBA/2J, CBA/Lac,
      C57BL/6, BALB/c, ICR, AKR/J, C3H and Asn) was performed and a significant effect
      of genotype was found. In the same eight mouse strains, functional activity of 5
      HT(1A) and 5-HT(3) receptors was studied. The comparison of hypothermic responses
      produced by 5-HT(7) receptor agonist LP44 (20.5 nmol, i.c.v.) and 5-HT(1A)
      receptor agonist 8-OH-DPAT 1.0 mg/kg, i.p. (3.0 MUmol/kg), 5-HT(3) receptor
      agonist m-CPBG (40.0 nmol, i.c.v.) did not reveal considerable interstrain
      correlations between 5-HT(7) and 5-HT(1A) or 5-HT(3) receptor-induced
      hypothermia. The selective 5-HT(7) receptor antagonist SB 269970 (16.1 fmol,
      i.c.v.) failed to attenuate the hypothermic effect of 8-OH-DPAT 1.0 mg/kg, i.p.
      (3.0 MUmol/kg) and m-CPBG (40.0 nmol, i.c.v.) indicating that the brain 5-HT(7)
      receptor is not involved in the hypothermic effects of 8-OH-DPAT or m-CPBG. The
      obtained results suggest that the central 5-HT(7) receptor plays an essential
      role in the mediation of thermoregulation independent of 5-HT(1A) and 5-HT(3)
      receptors.

PMID- 21884712
TI  - Attentional capture by emotional stimuli is preserved in patients with amygdala
      lesions.
AB  - The importance of cues signaling reward, threat or danger would suggest that they
      receive processing privileges in the neural systems underlying perception and
      attention. Previous research has documented enhanced processing of motivationally
      salient cues, and has pointed to the amygdala as a candidate neural structure
      underlying the enhancements. In the current study, we examined whether the
      amygdala was necessary for this emotional modulation of attention to occur.
      Patients with unilateral amygdala lesions and matched controls completed an
      emotional attentional blink task in which emotional distractors impair the
      perception of subsequent targets. Emotional images proved more distracting across
      all participant groups, including those with right or left amygdala lesions.
      These data argue against a central role for the amygdala in mediating all types
      of attentional capture by emotional stimuli.

PMID- 21884713
TI  - Sex differences in anxiety-like behavior and locomotor activity following
      prenatal and postnatal methamphetamine exposure in adult rats.
AB  - The aim of the present study was to investigate the impact of prenatal and
      postnatal methamphetamine (MA) exposure on behavior and anxiety in adult male and
      female rats. Mothers were daily exposed to injection of MA (5 mg/kg) or saline
      (S): prior to impregnation and throughout gestation and lactation periods. On
      postnatal day 1, pups were cross-fostered so that each mother raised 6 saline
      exposed pups and 6 MA-exposed pups. Based on the prenatal and postnatal exposure
      4 experimental groups (S/S, S/MA, MA/S, MA/MA) were tested in the Open field (OF)
      and in the Elevated plus maze (EPM) in adulthood. Locomotion, exploration,
      immobility and comforting behavior were evaluated in the OF, while anxiety was
      assessed in the EPM. While prenatal MA exposure did not affect behavior and
      anxiety in adulthood, postnatal MA exposure (i.e. MA administration to lactating
      mothers) induced long-term changes. Specifically, adult female rats in diestrus
      and adult males postnatally exposed to MA via breast milk (S/MA and MA/MA) had
      decreased locomotion and exploratory behavior in the OF and showed increased
      anxiety-like behavior in the EPM when compared to female rats in diestrus or
      males postnatally exposed to saline (S/S and MA/S). In adult females in
      proestrus, postnatal exposure to MA affected only exploratory behavior in the OF
      when compared to rats in proestrus postnatally exposed to saline. Thus, the
      present study shows that postnatal exposure to MA via breast milk impairs
      behavior in unfamiliar environment and anxiety-like behavior of adult male and
      female rats more than prenatal MA exposure.

PMID- 21884714
TI  - High HPA-axis activation disrupts the link between liking and wanting with liking
      and wanting related brain signaling.
AB  - BACKGROUND: Eating behavior changes under stress, i.e. during high HPA-axis
      activation. AIM: Assessment of effects of high versus low HPA-axis activation on
      liking and wanting related brain signaling in relevant regions. METHODS: 15
      female subjects (21.5+/-0.4 years, BMI=22.2+/-0.4) completed fMRI scans on 2
      days, in a fasted as well as a satiated condition on each day. The days were
      sorted by HPA-axis activation, resulting in two sufficiently separated HPA-axis
      states which were statistically confirmed (p<.05). During scans, subjects rated
      liking and wanting for food images; wanting indicated food choice for the
      subsequent meal. Energy-intake, hunger and fullness were additionally recorded.
      RESULTS: Hunger changed significantly over the meal (p<.001). Energy intake was
      lower during the second meal (p<.001). Behavioral wanting was lower after
      breakfast (p<.01), behavioral liking did not change. During low HPA-activation,
      liking task related signaling (TRS) pre-meal in the anterior insula predicted
      behavioral liking, wanting TRS in the anterior insula, nucleus accumbens and
      thalamus predicted behavioral wanting. During high HPA-activation, these
      relationships were not present pre-meal, but post-meal behavioral liking was
      predicted in the nucleus accumbens and wanting in the caudate. CONCLUSION: High
      HPA-axis activation disrupted and redirected the connection of behavioral
      liking/wanting with the specifically associated brain signaling in relevant
      regions.

PMID- 21884715
TI  - Survivor's dilemma: Defend the group or flee?
AB  - We consider a survival game of gregarious individuals, in which the aim of the
      players is survival to reproductive age under predator attacks. The survivor's
      dilemma (shortly: SVD) game consists in the following: a group member either
      surely survives alone by fleeing, while its defensive mate may be killed; or
      tries to save its mate's life, risking to get killed. The dilemma is that, in
      every single attack, fleeing ensures maximal survival probability, but if its
      mate survives by fighting both, and they remain together, its risk to be killed
      at the next attack will be lower. We show that, if defense is successful enough,
      then the one-attack game is a prisoner's dilemma (PD), where fleeing is the
      strict ESS. We have additively decomposed the SVD game, according to the survival
      of the group mate of the focal prey, into two games: the aim of the "collective
      game" is survival of the group of prey. Counter-wise, the aim of the "hostile
      game" is survival alone (focal prey survives and its mate is killed by the
      predator). We obtain the following results: if the attack number is large enough,
      the multi-attack SVD game is dominated by the "collective game" in the sense that
      each individual can ensure its own maximal survival probability by maximizing the
      group survival probability in each attack. In the hostile game, the only strict
      ESS is the fleeing strategy. In the collective game there are two different
      cases: either defense is a unique strict ESS, or the collective game is bistable,
      i.e. fleeing and defense are local strict ESS's. If defense is the only strict
      ESS in the collective game, and the attack number is large enough, defense
      replaces fleeing strategy in the multi-attack SVD game. However, in the bistable
      case, defense cannot invade into the fleeing population. It is shown that, if the
      interaction between relatives is frequent enough, than defense can replace
      fleeing strategy, in spite of the fact that in the well-mixed population the
      collective game is bistable.

PMID- 21884716
TI  - Organic anion transporting polypeptides in the hepatic uptake of PBDE congeners
      in mice.
AB  - BDE47, BDE99 and BDE153 are the predominant polybrominated diphenyl ether (PBDE)
      congeners detected in humans and can induce drug metabolizing enzymes in the
      liver. We have previously demonstrated that several human liver organic anion
      transporting polypeptides (humans: OATPs; rodents: Oatps) can transport PBDE
      congeners. Mice are commonly used to study the toxicity of chemicals like the
      PBDE congeners. However, the mechanism of the hepatic PBDE uptake in mice is not
      known. Therefore, the purpose of the current study was to test the hypothesis
      that BDE47, BDE99, and BDE153 are substrates of mouse hepatic Oatps (Oatp1a1,
      Oatp1a4, Oatp1b2, and Oatp2b1). We used Human Embryonic Kidney 293 (HEK293) cells
      transiently expressing individual Oatps and quantified the uptake of BDE47,
      BDE99, and BDE153. Oatp1a4, Oatp1b2, and Oatp2b1 transported all three PBDE
      congeners, whereas Oatp1a1 did transport none. Kinetic studies demonstrated that
      Oatp1a4 and Oatp1b2 transported BDE47 with the greatest affinity, followed by
      BDE99 and BDE153. In contrast, Oatp2b1 transported all three PBDE congeners with
      similar affinities. The importance of hepatic Oatps for the liver accumulation of
      BDE47 was confirmed using Oatp1a4-, and Oatp1b2-null mice.

PMID- 21884717
TI  - Puerarin activates endothelial nitric oxide synthase through estrogen receptor
      dependent PI3-kinase and calcium-dependent AMP-activated protein kinase.
AB  - The cardioprotective properties of puerarin, a natural product, have been
      attributed to the endothelial nitric oxide synthase (eNOS)-mediated production of
      nitric oxide (NO) in EA.hy926 endothelial cells. However, the mechanism by which
      puerarin activates eNOS remains unclear. In this study, we sought to identify the
      intracellular pathways underlying eNOS activation by puerarin. Puerarin induced
      the activating phosphorylation of eNOS on Ser1177 and the production of NO in
      EA.hy926 cells. Puerarin-induced eNOS phosphorylation required estrogen receptor
      (ER)-mediated phosphatidylinositol 3-kinase (PI3K)/Akt signaling and was reversed
      by AMP-activated protein kinase (AMPK) and calcium/calmodulin-dependent kinase II
      (CaMKII) inhibition. Importantly, puerarin inhibited the adhesion of tumor
      necrosis factor (TNF)-alpha-stimulated monocytes to endothelial cells and
      suppressed the TNF-alpha induced expression of intercellular cell adhesion
      molecule-1. Puerarin also inhibited the TNF-alpha-induced nuclear factor-kappaB
      activation, which was attenuated by pretreatment with N(G)-nitro-L-arginine
      methyl ester, a NOS inhibitor. These results indicate that puerarin stimulates
      eNOS phosphorylation and NO production via activation of an estrogen receptor
      mediated PI3K/Akt- and CaMKII/AMPK-dependent pathway. Puerarin may be useful for
      the treatment or prevention of endothelial dysfunction associated with diabetes
      and cardiovascular disease.

PMID- 21884718
TI  - DNA base excision repair gene polymorphisms modulate human cognitive performance
      and decline during normal life span.
AB  - To test the hypothesis that single nucleotide polymorphisms (SNPs) in DNA repair
      genes are associated with cognitive performance during normal aging, the
      relationship between SNPs in selected exons in DNA base excision repair (BER)
      genes and cognitive performance was examined in 712 healthy Norwegian individuals
      aged 20-75 years. SNPs examined included PolB(Pro242Arg), hOGG1(Ser326Cys), MutYH
      (Met22Val), MutYH(His324Gln), APE1(Gln51His), APE1(Glu148Asp), XRCC1(Lys298Asn),
      XRCC1(Arg7Leu), NEIL1(Asp252Asn), and NEIL2(Arg257Leu). XRCC1(Arg7Leu) and
      PolB(Pro242Arg) were characterized by single nucleotide variations (<=0.1%
      homozygote SNPs). hOGG1(Ser326Cys) (Ser/Cys 40.8%/Cys/Cys 5.7%), MutYH(His324Gln)
      (His/Gln37%/Gln/Gln 6.0%) and APE1(Glu148Asp) (Glu/Asp 51.3%/Asp/Asp 23.0%) were
      characterized by higher SNP frequencies. MutYH(Met22Val), APE1(Gln51His) and
      NEIL2(Arg257Leu) occurred at intermediate SNP frequencies of 11.5, 7.6 and 5.3%,
      respectively. Interestingly, hOGG1(Ser326Cys) and APE1(Gln51His) had genotype by
      age interactions with general cognitive function, reasoning, control and speed of
      processing in cross-sectional analysis and a significant effect on longitudinal
      decline. Dispersed association effects involving MutYH(His324Gln),
      MutYH(Met22Val), PolB(Pro242Arg) and NEIL2(Arg257Leu) were also detected when
      APOE or CHRNA4, were included in the statistical model, a result consistent with
      proposed involvement of the latter markers in human cognitive decline and/or
      function. In summary, the results support the notion that polymorphisms in BER
      genes modulate cognitive performance in healthy elderly individuals.

PMID- 21884719
TI  - Increased longevity of some C. elegans mitochondrial mutants explained by
      activation of an alternative energy-producing pathway.
AB  - The Caenorhabditis elegans misc-1 gene encodes a mitochondrial carrier with a
      role in oxidative stress response. The knock-out mutant has no lifespan phenotype
      and fails to upregulate the gei-7-mediated glyoxylate shunt, an extra
      mitochondrial pathway of energy production. We show that gei-7 is required for
      the longevity of the mitochondrial mutant clk-1. Our data suggest that only
      mitochondrial mutants that upregulate gei-7 can achieve longevity.

PMID- 21884720
TI  - Characterizing the subjective and psychomotor effects of carisoprodol in healthy
      volunteers.
AB  - Carisoprodol is a centrally acting drug used to relieve skeletal muscle spasms
      and associated pain in acute musculoskeletal conditions. There is evidence from
      different sources that this oral muscle relaxant is abused and that it is
      associated with impairment leading to arrests for "driving under the influence"
      as well as increased risk of automobile accidents. Its subjective and psychomotor
      effects in healthy volunteers at therapeutic and supratherapeutic doses have not
      been well-characterized, and form the basis of this report. Fifteen healthy
      volunteers (8 males, 7 females) were administered 0, 350, and 700 mg of
      carisoprodol in separate sessions and for 6h afterwards they completed a battery
      of tests at fixed time intervals so as to assess the subjective and psychomotor
      effects of the drug. The supratherapeutic dose, 700 mg, increased visual analog
      scale ratings of terms that were more reflective of sedation (e.g., "sleepy,"
      "heavy, sluggish feeling") than those of abuse liability, and produced impaired
      performance on several psychomotor tests. The therapeutic dose, 350 mg, while
      producing few and mild subjective effects, still produced psychomotor impairment.
      The fact that the therapeutic dose of carisoprodol produced minimal subjective
      effects while adversely affecting performance is of concern in that patients
      prescribed this drug may feel relatively normal and engage in tasks (driving)
      that could put themselves and others at risk.

PMID- 21884721
TI  - Are cultural values and beliefs included in U.S. based HIV interventions?
AB  - OBJECTIVE: To determine the extent to which current United States based human
      immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) prevention
      and risk reduction interventions address and include aspects of cultural beliefs
      in definitions, curricula, measures and related theories that may contradict
      current safer sex messages. METHOD: A comprehensive literature review was
      conducted to determine which published human immunodeficiency virus/acquired
      immune deficiency syndrome (HIV/AIDS) prevention and risk reduction interventions
      incorporated aspects of cultural beliefs. RESULTS: This review of 166 human
      immunodeficiency virus (HIV) prevention and risk reduction interventions,
      published between 1988 and 2010, identified 34 interventions that varied in
      cultural definitions and the integration of cultural concepts. CONCLUSION: human
      immunodeficiency virus (HIV) interventions need to move beyond targeting specific
      populations based upon race/ethnicity, gender, sexual, drug and/or risk behaviors
      and incorporate cultural beliefs and experiences pertinent to an individual's
      risk. Theory based interventions that incorporate cultural beliefs within a
      contextual framework are needed if prevention and risk reduction messages are to
      reach targeted at risk populations. Implications for the lack of uniformity of
      cultural definitions, measures and related theories are discussed and
      recommendations are made to ensure that cultural beliefs are acknowledged for
      their potential conflict with safer sex skills and practices.

PMID- 21884722
TI  - Predicting what will happen when we act. What counts for warrant?
AB  - To what extent do the results of randomized controlled trials inform our
      predictions about the effectiveness of potential policy interventions? This
      crucial question is often overlooked in discussions about evidence-based policy.
      The view I defend is that the arguments that lead from the claim that a program
      works somewhere to a prediction about the effectiveness of this program as it
      will be implemented here rests on many premises, most of which cannot be
      justified by the results of randomized controlled trials. Randomized controlled
      trials only provide indirect evidence for effectiveness, and we need much more
      than just randomized- controlled-trial results to make reliable predictions.

PMID- 21884723
TI  - "If there wasn't the technology then I would probably be out everyday": a
      qualitative study of children's strategies to reduce their screen viewing.
AB  - OBJECTIVE: To explore the views of British 10-11 year old children towards
      reducing their screen-viewing and their screen-viewing reduction strategies.
      METHOD: 10 focus groups were conducted with 55 10-11 year old children (30 girls,
      25 boys) in Bristol (UK) in 2010. Data were transcribed and transcripts were
      analysed using thematic analysis. RESULTS: Three main themes were developed:
      Reaction to Reduction; Reduction: What, when and what else instead?; and
      Strategies to reduce screen-viewing. Participants reacted largely positively to
      reducing their screen-viewing although enjoyment, established routines and
      favourite TV programmes presented barriers. A range of screen-viewing modes were
      put forward as candidates for reduction and participants believed they would
      replace screen-viewing with both physically active and non-screen sedentary
      behaviours. Reduction strategies identified comprised the provision of
      alternative activities, facilities and after school clubs, peer-led educational
      interventions, behavioural strategies such as the use of rewards, charts and time
      limits which involved children's parents and parent-child collaboration.
      Unexpectedly, participants identified the focus group itself as a means of
      encouraging self-reflection and initiating change. CONCLUSION: Children appeared
      open to screen-viewing reduction and identified the strategies that they may
      respond to best. This can inform the development of interventions designed to
      reduce screen-viewing.

PMID- 21884724
TI  - Working with cancer: health and disability disparities among employed cancer
      survivors in the U.S.
AB  - INTRODUCTION: Approximately 40% of Americans annually diagnosed with cancer are
      working-age adults. Using a nationally representative database, we characterized
      differences in health status and occupation of working cancer survivors and
      persons without cancer. METHODS: Cross-sectional data pooled from the 1997-2009
      US National Health Interview Survey for adults with self-reported physician
      diagnosed cancer (n=22,952) and those without (n=358,495), were analyzed.
      Multivariable logistic regression was used to compare the health and disability
      status of employed cancer survivors across occupational sectors relative to
      workers without a cancer history and unemployed cancer survivors. RESULTS:
      Relative to workers with no cancer history, cancer survivors were more likely
      (OR; 95%CI) to be white-collar workers and less likely to be service workers.
      Working cancer survivors were significantly less likely than unemployed
      survivors, but more likely than workers with no cancer history, to report poor
      fair health (0.25; 0.24-0.26) and (2.06; 1.96-2.17) respectively, and >= 2
      functional limitations (0.37; 0.35-0.38) and (1.72; 1.64-1.80) respectively.
      Among employed cancer survivors, blue-collar workers reported worse health
      outcomes, yet they reported fewer workdays missed than white-collar workers.
      CONCLUSION: Blue-collar cancer survivors are working with high levels of poor
      health and disability. These findings support the need for workplace
      accommodations for cancer survivors in all occupational sectors, especially blue
      collar workers.

PMID- 21884725
TI  - Prolactin-induced activation of phagocyte NADPH oxidase in the teleost fish
      gilthead seabream involves the phosphorylation of p47phox by protein kinase C.
AB  - The pituitary hormone prolactin (PRL) is a multifunctional polypeptide which act
      as a key component of the neuroendocrine-immune loop and as a local regulator of
      the macrophage response. The involvement of PRL in regulating monocyte/macrophage
      functions is suggested by the presence of PRL receptors in these cells. Recently,
      we reported that physiological concentrations of native PRL were able to induce
      the expression of the pro-inflammatory cytokines IL-1beta and TNFalpha, and the
      production of reactive oxygen species (ROS) in head kidney leukocytes and
      macrophages from the teleost fish gilthead seabream (Sparus aurata L.). In this
      study, we show that the NADPH oxidase subunit p47phox becomes phosphorylated in
      leukocytes stimulated with PRL, an effect that is blocked when neutralizing
      polyclonal antibodies to PRL are added. Additionally, the pharmacological
      inhibition of either protein kinase C (PKC) with calphostin C or the Jak/Stat
      signaling pathway with AG490 impaired PKC activation, p47phox phosphorylation and
      ROS production in seabream leukocytes activated with PRL. Taken together, our
      results demonstrate for the first time the need for PKC in regulating the PRL
      mediated phosphorylation of p47phox, the activation of NADPH oxidase and the
      production of ROS by macrophages in vertebrates.

PMID- 21884726
TI  - Serratia septicaemia in pregnancy: further evidence of altered immune response to
      severe bacterial infection in pregnancy.

PMID- 21884727
TI  - Automated sleep scoring in rats and mice using the naive Bayes classifier.
AB  - We describe a new simple MATLAB-based method for automated scoring of rat and
      mouse sleep using the naive Bayes classifier. This method is highly sensitive
      resulting in overall auto-rater agreement of 93%, comparable to an inter-rater
      agreement between two human scorers (92%), with high sensitivity and specificity
      values for wake (94% and 96%), NREM sleep (94% and 97%) and REM sleep (89% and
      97%) states. In addition to baseline sleep-wake conditions, the performance of
      the naive Bayes classifier was assessed in sleep deprivation and drug infusion
      experiments, as well as in aged and transgenic animals using multiple EEG
      derivations. 24-h recordings from 30 different animals were used, with
      approximately 5% of the data manually scored as training data for the
      classification algorithm.

PMID- 21884728
TI  - Detection by PCR of human papillomavirus in Colombia: Comparison of GP5+/6+ and
      MY09/11 primer sets.
AB  - The aims of this study were to determine the prevalence of HPV infection and
      evaluate the concordance and performance of two primer sets for detecting single
      and multiple viral infections. A total of 1810 Colombian women were enrolled in
      the study, and molecular, cytological and epidemiological analyses were
      performed. Both concordance and performance of two different PCR amplification
      primer sets (GP5+/6+ and MY09/11) were assessed. The results showed that 60.2% of
      females with positive HPV DNA were infected by more than one viral type. The OR
      for multiple infections was 18.2 when using the MY09/11 primer set and 6.52 with
      the GP5+/6+ primer set. The results also showed an association between GP5+/6+
      positivity and the severity of the disease regarding the cytological findings. It
      was also found that using a single primer set led to underestimating the
      prevalence for HPV infection. The simultaneous use of these primer sets is an
      important tool for the detection of HPV DNA, being equally relevant for
      identifying multiple infections and low viral DNA copies. This study highlights
      the importance of suitable assessment of HPV epidemiological profiles; screening
      programs must also be strengthened to broaden the coverage of the most vulnerable
      populations.

PMID- 21884729
TI  - Assessing aphids potato virus Y-transmission efficiency: A new approach.
AB  - In order to develop an alternative method to optimize the relative efficiency
      factor (REF) assessment, the efficiency of transmission of Potato virus Y (PVY)
      by seven aphid species was examined. In vitro micropropagated potato plantlets
      were used to experiment on phenotypically and genetically homogeneous material.
      Species-specific acquisition access period (AAP) on a PVY-infected plantlet was
      assessed for each aphid species using electrical penetration graph (EPG)
      technique. Aphid probing behaviour determined by EPG showed that Macrosiphum
      euphorbiae and Myzus persicae exhibited the shortest AAPs (15 and 11min,
      respectively) whereas Rhopalosiphum padi, Sitobion avenae, Brevicoryne brassicae
      and Acyrthosiphon pisum exhibited the longest ones (more than 30min). The
      transmission rate obtained for M. persicae (83.3%) was higher than the ones
      reported in the literature. REFs assessment showed that A. pisum and B. brassicae
      were poor efficient vectors while M. euphorbiae and S. avenae seemed to be
      efficient ones even though their respective REF were significantly lower than
      that of M. persicae. The species R. padi and A. fabae did not transmit PVY. The
      hypothesis assessed for M. euphorbiae and S. avenae and consisting in the
      compensation of a weak PVY-transmission efficiency by a higher number of vectors,
      was not supported. The use of this new method for REF evaluation and the need to
      consider aphid behaviour for such an assessment was discussed.

PMID- 21884730
TI  - Behavioural and cellular effects of exogenous amyloid-beta peptides in rodents.
AB  - A better understanding of Alzheimer's disease (AD) and the development of disease
      modifying therapies are some of the biggest challenges of the 21st century. One
      of the core features of AD are amyloid plaques composed of amyloid-beta (Abeta)
      peptides. The first hypothesis proposed that cognitive deficits are linked to
      plaque-development and transgenic mice have been generated to study this link,
      thereby providing a good model to develop new therapeutic approaches. Since later
      it was recognised that in AD patients the cognitive deficit is rather correlated
      to soluble amyloid levels, consequently, a new hypothesis appeared associating
      the earliest amyloid toxicity to these soluble species. The purpose of this
      review is to give a summary of behavioural and cellular data obtained after
      soluble Abeta peptide administration into rodents' brain, thereby showing that
      this model is a valid tool to investigate AD pathology when no plaques are
      present. Additionally, this method offers an excellent, efficient model to test
      compounds which could act at such early stages of the disease.

PMID- 21884731
TI  - A mixture of odorant molecules potentially indicating oestrus in mammals elicits
      penile erections in male rats.
AB  - A common set of odorous molecules may indicate female receptiveness across
      species, as male rats display sexual arousal when exposed to the odour of
      oestrous faeces from rats, vixens and mares. More than 900 different compounds
      were identified by GC-MS analyses performed on faeces samples from di-oestrous
      and oestrous females and from males of the three species. Five carboxylic acids
      were found in lower concentrations in faeces from all oestrous females. We
      subjected 12 sexually trained male rats to a 30 min exposure to different
      dilutions of a mixture of these five molecules in the same proportions as found
      in female oestrous faeces. The behavioural responses of the rats were compared to
      those displayed when exposed to water (negative control) and faeces from oestrous
      female rats (positive control). Frequency of penile erections were found to be
      significantly dependent on mixture dilution, with two intermediate dilutions
      eliciting frequencies of penile erections that did not differ from those obtained
      during exposure to oestrous female rat faeces. Higher and lower dilutions did not
      elicit more penile erections than observed with water. These results support our
      hypothesis that a small set of odorous molecules may indicate sexual
      receptiveness in mammalian females.

PMID- 21884732
TI  - Cortisol awakening response: are sampling delays of 15 minutes acceptable?
AB  - Cortisol awakening responses (CAR) are often blunted or even extinguished when
      saliva samplings are delayed. The literature suggests that delays of 10 or 15 min
      are tolerable. Delays of 15 min were analysed with 510 CARs with the first sample
      taken within 3 min post-awakening followed by 4 samples taken 15, 30, 45, and 60
      min later. Varying delays of up to 30 min were analysed with these and further
      148 CARs where sampling began within 30 min post-awakening. Times of awakening
      and of saliva collection were verified by polysomnography or actimetry and by
      electronic devices respectively. Simulated sampling delays of 15 min revealed
      highly significant deviations from correctly taken CARs. No deviations were found
      for delays of up to 11.5 min suggesting that delays of up to 10 min are
      acceptable but that delays between 10 and 15 min might become critical.

PMID- 21884733
TI  - Improved activity and stability of Rhizopus oryzae lipase via immobilization for
      citronellol ester synthesis in supercritical carbon dioxide.
AB  - In present work, Rhizopus oryzae lipase immobilized on a film prepared using
      blend of hydroxylpropyl methyl cellulose (HPMC) and polyvinyl alcohol (PVA) was
      investigated for synthesis of citronellol esters with supercritical carbon
      dioxide (Sc-CO(2)) as a reaction medium. The transesterification reaction was
      optimized for various reaction parameters like effect of molar ratio, acyl donor,
      time, temperature, enzyme concentration, effect of pressure and co-solvent to
      achieve the maximum yield of desired product. The results obtained signify
      remarkable increment (about eightfold) in the yield of citronellol acetate (91%)
      as compared to that of free lipase (11%) in Sc-CO(2). The developed biocatalytic
      methodology provides a substantial advantage of low biocatalyst loading (1.5%,
      w/v), lower reaction temperature (45 degrees C) and lower pressure (8 MPa) as
      compared to previous reports. The immobilization method has significantly
      enhanced the operational stability of lipase for ester synthesis under Sc-CO(2)
      conditions. The developed methodology was successfully applied for synthesis of
      three different industrially important citronellol esters namely citronellol
      acetate (91%), citronellol butyrate (98%), citronellol laurate (99%) with
      excellent yields using vinyl esters as acyl donor under Sc-CO(2) conditions. In
      addition, the immobilized biocatalyst was effectively recycled for three
      consecutive recycles.

PMID- 21884734
TI  - Inhibition effect of isopropanol on acetyl-CoA synthetase expression level of
      acetoclastic methanogen, Methanosaeta concilii.
AB  - Isopropanol is a widely found solvent in industrial wastewaters, which have
      commonly been treated using anaerobic systems. In this study, inhibitory effect
      of isopropanol on the key microbial group in anaerobic bioreactors, acetoclastic
      methanogens, was investigated. Anaerobic sludges in serum bottles were repeatedly
      fed with acetate and isopropanol; and quantitative real-time PCR was used for
      determining effect of isopropanol on the expression level of a key enzyme in
      acetoclastic methane production, acetyl-CoA synthetase of Methanosaeta concilii.
      Active Methanosaeta spp. cells were also quantified using Fluorescent in situ
      hybridization (FISH). Transcript abundance of acetyl-CoA synthetase was 1.23+/
      0.62*10(6) mRNAs/mL in the uninhibited reactors with 222 mL cumulative methane
      production. First exposure to isopropanol resulted in 71.2%, 84.7%, 89.2% and
      94.6% decrease in mRNA level and 35.0%, 65.0%, 91.5% and 100.0% reduction in
      methane production for isopropanol concentrations of 0.1 M, 0.5 M, 1.0 M and 2.0
      M, respectively. Repeated exposures resulted in higher inhibitions; and at the
      end of test, fluorescent intensities of active Methanosaeta cells were
      significantly decreased due to isopropanol. The overall results indicated that
      isopropanol has an inhibitory effect on acetoclastic methanogenesis; and the
      inhibition can be detected by monitoring level of acetyl-CoA transcripts and rRNA
      level.

PMID- 21884735
TI  - Mechanisms governing the responses to anthracnose pathogen in Juglans spp.
AB  - Juglans nigra and Juglans regia are two highly economically important species for
      wood and fruit production that are susceptible to anthracnose caused by Gnomonia
      leptostyla. The identification of genotypes resistant to anthracnose could
      represent a valid alternative to agronomic and chemical management. In this
      study, we analyzed 72 walnut genotypes that showed a variety of resistance
      phenotypes in response to natural infection. According to the disease severity
      rating and microsatellite fingerprinting analysis, these genotypes were divided
      into three main groups: (40) J. nigra resistant, (1) J. nigra susceptible, and
      (31) J. regia susceptible. Data on leaf emergence rates and analysis of in vivo
      pathogenicity indicated that the incidence of anthracnose disease in the field
      might be partially conditioned by two key factors: the age and/or availability of
      susceptible leaves during the primary infection of fungus (avoidance by late
      flushing) and partial host resistance. NBS profiling approach, based on PCR
      amplification with an adapter primer for an adapter matching a restriction enzyme
      site and a degenerate primer targeting the conserved motifs present in the NBS
      domain of NBS-LRR genes, was applied. The results revealed the presence of a
      candidate marker that correlated to a reduction in anthracnose incidence in 72
      walnut genotypes.

PMID- 21884736
TI  - High level expression of human enteropeptidase light chain in Pichia pastoris.
AB  - Human enterokinase (enteropeptidase, rhEP), a serine protease expressed in the
      proximal part of the small intestine, converts the inactive form of trypsinogen
      to active trypsin by endoproteolytic cleavage. The high specificity of the target
      site makes enterokinase an ideal tool for cleaving fusion proteins at defined
      cleavage sites. The mature active enzyme is comprised of two disulfide-linked
      polypeptide chains. The heavy chain anchors the enzyme in the intestinal brush
      border membrane, whereas the light chain represents the catalytic enzyme subunit.
      The synthetic gene encoding human enteropeptidase light chain with His-tag added
      at the C-terminus to facilitate protein purification was cloned into Pichia
      pastoris expression plasmids under the control of an inducible AOX1 or
      constitutive promoters GAP and AAC. Cultivation media and conditions were
      optimized as well as isolation and purification of the target protein. Up to 4
      mg/L of rhEP was obtained in shake-flask experiments and the expression level of
      about 60-70 mg/L was achieved when cultivating in lab-scale fermentors. The
      constitutively expressing strains proved more efficient and less labor-demanding
      than the inducible ones. The rhEP was immobilized on AV 100 sorbent (Iontosorb)
      to allow repeated use of enterokinase, showing specific activity of 4U/mL of wet
      matrix.

PMID- 21884738
TI  - Pepino mosaic virus capsid protein interacts with a tomato heat shock protein
      cognate 70.
AB  - Plant viral capsid proteins (CP) can be involved in virus movement, replication
      and symptom development as a result of their interaction with host factors. The
      identification of such interactions may thus provide information about viral
      pathogenesis. In this study, Pepino mosaic virus (PepMV) CP was used as bait to
      screen a tomato (Solanum lycopersicum) cDNA library for potential interactors in
      yeast. Of seven independent interacting clones, six were predicted to encode the
      C-termini of the heat shock cognate 70 (Hsc70) proteins. Three full length tomato
      Hsc70s (named Hsc70.1, .2, .3) were used to confirm the interaction in the yeast
      two hybrid assay and bimolecular fluorescent complementation (BiFC) in planta.
      The PepMV CP-Hsc70 interaction was confirmed only in the case of Hsc70.3 for both
      assays. In BiFC, the interaction was visualized in the cytoplasm and nucleus of
      agroinfiltrated Nicotiana benthamiana epidermal cells. During PepMV infection,
      Hsc70.3 mRNA levels were induced and protein accumulation increased at 48 and 72
      h post inoculation. In transmission electron microscopy using immunogold
      labelling techniques, Hsc70 was detected to co-localize with virions in the
      phloem of PepMV-infected tomato leaves. These observations, together with the co
      purification of Hsc70 with PepMV virions further support the notion of a PepMV
      CP/Hsc70 interaction during virus infection.

PMID- 21884737
TI  - Conserved and variable structural elements in the 5' untranslated region of two
      hypoviruses from the filamentous fungus Cryphonectria parasitica.
AB  - Virulence-attenuating viruses (hypoviruses) of the filamentous fungus
      Cryphonectria parasitica, the causative agent of chestnut blight, have become a
      premier model for understanding the molecular biology of mycoviruses. However, a
      major gap exists in current understanding of structure and function of the
      untranslated regions (UTRs) of the hypovirus RNA genome, despite considerable
      evidence that secondary and tertiary UTR structure plays a crucial role in the
      control of translation and genome replication in other systems. In this study we
      have used structure prediction software coupled with RNase digestion studies to
      develop validated structural models for the 5' UTRs of the two best-characterized
      members of the Hypoviridae, CHV1-EP713 and CHV1-Euro7. These two hypovirus
      strains exhibit significant variation in virulence attenuation despite sharing
      >90% sequence identity. Our models reveal highly structured regions in the 5' UTR
      of both strains, with numerous stem-loops suggestive of internal ribosome entry
      sites. However, considerable differences in the size and complexity of structural
      elements exist between the two strains. These data will guide future, mutagenesis
      based studies of the structural requirements for hypovirus genome replication and
      translation.

PMID- 21884739
TI  - Tumour necrosis factor-alpha increases extravasation of virus particles into
      tumour tissue by activating the Rho A/Rho kinase pathway.
AB  - Tumour Necrosis Factor alpha (TNF) is a pleiotropic pro-inflammatory cytokine
      with known vascular permeabilising activity. It is employed during isolated limb
      perfusion to enhance delivery of chemotherapeutic drugs into tumour tissue. The
      use of conditionally-replicating lytic viruses, so called 'oncolytic
      virotherapy', provides a new approach to cancer treatment that is currently
      limited by the low efficiency of extravasation of viral particles into tumours.
      We report here evidence that TNF significantly enhances the delivery of virus
      particles through the endothelial layer to allow access to tumour cells both in
      vitro and in vivo. Intravenous administration of TNF resulted in a 3- to 6-fold
      increase in EL4 tumour uptake of Evans Blue/Albumin, adenovirus and long
      circulating polymer coated adenovirus. Interestingly, endothelial
      permeabilisation could be suppressed in vitro and in vivo by Y-27632, a Rho
      kinase inhibitor, without inhibiting viral infection. These data indicate that
      TNF can enhance the delivery of virus particles into tumours through a Rho A/Rho
      kinase dependent mechanism and may be a valuable strategy for increasing the
      delivery of oncolytic viruses and other therapeutic agents.

PMID- 21884740
TI  - Biophysical properties of chitosan/siRNA polyplexes: profiling the polymer/siRNA
      interactions and bioactivity.
AB  - Chitosans are naturally occurring polymers widely used in life science to mediate
      intracellular uptake of nucleic acids such as siRNA. Four chitosans of fungal
      origin (Agaricus bisporus; molecular weights MW=44, 63, 93 and 143 kDa) were used
      in this study and profiled for size, viscosity and hydrodynamic radius using gel
      permeation chromatography (GPC). Polyplexes made of these chitosans and siRNA
      were developed and optimized for transfection efficacy in vitro. The
      characteristics of these polyplexes were low chitosan:siRNA ratios (4-8; N:P)
      similar positive zeta potential (20-30 mV) and comparable particle sizes (about
      150 nm). Endogenous luciferase reporter gene down-regulation in human epithelial
      H1299 cells at nanomolar concentrations (37.5-150 nM) was significantly stronger
      for the lower molecular weight chitosans. The impact of these low N:P polyplexes
      on the cellular viability was minimal also at 150 nM. To help develop an
      understanding of these differences, an energetic profile of the molecular
      interactions and polyplex formation was established by isothermal titration
      calorimetry (ITC). The four polyplexes exhibited strong binding enthalpies delta
      H(bind)(-84 to -102 kcal/mol) resulting in nanomolar dissociation constants.
      Intracellular trafficking studies using rhodamine labeled siRNA revealed that
      polyplexes made from smaller MW chitosans exhibited faster cellular uptake
      kinetics than their higher MW counterpart. Transmission electron microscopy and
      small angle X-ray scattering studies (SAXS) revealed that the 44 kDa derived
      polyplexes exhibited regular spherical structure, whereas the 143 kDa chitosan
      polyplex was rather irregularly shaped. With regards to adverse effects these low
      N:P chitosan/siRNA formulations represent an interesting alternative to so far
      reported chitosan polyplexes that used vast N:P excess to achieve similar
      bioactivity.

PMID- 21884742
TI  - Structural and biological characterization of mastoparans in the venom of Vespa
      species in Taiwan.
AB  - Mastoparans, a family of small peptides, are isolated from the wasp venom. In
      this study, six mastoparans were identified in the venom of six Vespa species in
      Taiwan. The precursors of these mastoparans are composed of N-terminal signal
      sequence, prosequence, mature mastoparan, and appendix glycine at C-terminus.
      These mature mastoparans all have characteristic features of linear cationic
      peptides rich in hydrophobic and basic amino acids without disulfide bond.
      Therefore, these peptides could be predicted to adopt an amphipathic alpha
      helical secondary structure. In fact, the CD (circular dichroism) spectra of
      these peptides show a high content alpha-helical conformation in the presence of
      8 mM SDS or 40% 2,2,2-trifluoroethanol (TFE). All mastoparans exhibit mast cell
      degranulation activity, antimicrobial activity against both Gram-positive and 
      negative bacteria tested, various degree of hemolytic activity on chicken, human,
      and sheep erythrocytes as well as membrane permeabilization on Escherichia coli
      BL21. Our results also show that the hemolytic activity of mastoparans is
      correlated to mean hydrophobicity and mean hydrophobic moment.

PMID- 21884741
TI  - Parental feeding behaviours and motivations. A qualitative study in mothers of UK
      pre-schoolers.
AB  - Parental feeding behaviours are considered major influences on children's eating
      behaviour. However, many questionnaire studies of feeding neglect subtle
      distinctions between specific feeding strategies and practices in favour of
      eliciting general feeding goals, and do not take account of the context provided
      by parents' motivations. These factors may be critical to understanding child
      outcomes and engaging parents in child obesity prevention. The present study
      obtained interview and diary data on specific feeding behaviours and underlying
      motivations from 22 mothers of predominantly healthy weight 3-5 y olds in the UK.
      Parents described a wide range of efforts to promote or restrict intake that were
      largely motivated by practical and health considerations and only rarely by
      concern about weight. There was also evidence for instrumental feeding, rules
      surrounding meal-time, child involvement, and parental flexibility in relation to
      feeding. Almost all parents described responding to children's appetitive traits,
      consistent with growing evidence for genetically influenced individual
      differences in children's appetite. These findings suggest that in order to
      engage parents of currently healthy weight children, obesity prevention advice
      should aim to satisfy their primary motivations (practicality, health), and be
      framed as helping parents to respond sensitively and appropriately to different
      children's characteristics.

PMID- 21884743
TI  - B-type natriuretic peptide and anthropometric measures in a Brazilian elderly
      population with a high prevalence of Trypanosoma cruzi infection.
AB  - B-type natriuretic peptide (BNP) is a diagnostic and prognostic tool in heart
      failure and also in Chagas disease, which is caused by the protozoan Trypanosoma
      cruzi and has cardiomyopathy as a main feature. BNP lipolytic actions and T.
      cruzi infection in the adipose tissue have been recently described. We aim to
      investigate the relationship between BNP and anthropometric measures and whether
      it is influenced by T. cruzi infection. We measured BNP, body mass index (BMI),
      waist circumference (WC), triceps skin-fold thickness (TSF) and performed
      serological, biochemical and electrocardiographic exams in 1398 subjects (37.5%
      infected with T. cruzi) in a community-dwelling elderly population in Bambui
      city, Brazil. Linear multivariate regression analysis was performed to
      investigate determinants of BNP levels. BNP levels were significantly (p<0.05)
      higher in T. cruzi-infected subjects than in the non-infected group (median=121
      and 64pg/mL, respectively). BMI, WC and TSF in infected subjects were
      significantly lower than those in non-infected subjects (24.3 vs. 25.5kg/m2; 89.2
      vs. 92.4cm; and 14.5 vs. 16.0mm, respectively). There was an inverse relationship
      between BNP levels and BMI (b=-0.018), WC (b=-0.005) and TSF (b=-0.193) levels.
      Infected and non-infected groups showed similar inverse relationships between BNP
      and BMI (b=-0.021 and b=-0.015, respectively). In conclusion, there was an
      inverse relationship between BNP levels and the anthropometric measures. Despite
      the actions in the adipose tissue, T. cruzi infection did not modify the
      associations between BNP and BMI, suggesting that body mass does not modify the
      accuracy of BNP in Chagas disease.

PMID- 21884744
TI  - Expression profiling reveals differential gene induction underlying specific and
      non-specific memory for pheromones in mice.
AB  - Memory for the mating male's pheromones in female mice is thought to require
      synaptic changes in the accessory olfactory bulb (AOB). Induction of this memory
      depends on release of glutamate in response to pheromonal exposure coincident
      with release of norepinephrine (NE) in the AOB following mating. A similar memory
      for pheromones can also be induced artificially by local infusion of the GABA(A)
      receptor antagonist bicuculline into the AOB. The natural memory formed by
      exposure to pheromones during mating is specific to the pheromones sensed by the
      female during mating. In contrast, the artificial memory induced by bicuculline
      is non-specific and results in the female mice recognizing all pheromones as if
      they were from the mating male. Although protein synthesis has been shown to be
      essential for development of pheromone memory, the gene expression cascades
      critical for memory formation are not known. We investigated changes in gene
      expression in the AOB using oligonucleotide microarrays during mating-induced
      pheromone memory (MIPM) as well as bicuculline-induced pheromone memory (BIPM).
      We found the set of genes induced during MIPM and BIPM are largely non
      overlapping and Ingenuity Pathway Analysis revealed that the signaling pathways
      in MIPM and BIPM also differ. The products of genes induced during MIPM are
      associated with synaptic function, indicating the possibility of modification at
      specific synapses, while those induced during BIPM appear to possess neuron-wide
      functions, which would be consistent with global cellular changes. Thus, these
      results begin to provide a mechanistic explanation for specific and non-specific
      memories induced by pheromones and bicuculline infusion respectively.

PMID- 21884745
TI  - Tumor-infiltrating lymphocytes and dendritic cells in human colorectal cancer:
      their relationship to KRAS mutational status and disease recurrence.
AB  - The prognosis of newly diagnosed colorectal cancer patients relies mostly on
      tumor-node metastasis classification. However, analyses of tumor-infiltrating
      lymphocytes and several molecular markers have also shown promising prognostic
      value. Mutations in the proto-oncogene KRAS, which occur early in colorectal
      carcinogenesis, have been demonstrated to be common in human colorectal cancer
      (CRC); however, their prognostic significance remains controversial. We examined
      the correlations between KRAS mutational status and tumor-infiltrating immune
      cells with respect to CRC recurrence. Mutations in KRAS were identified in 45.5%
      of the primary carcinomas in our cohort of patients: 65% in codon 12 and 35% in
      codon 13. Although codon 13 KRAS mutations were associated with disease relapse,
      they were present in both disease-free and relapsed patients. However, disease
      free and relapsed patients differed markedly in their patterns of tumor
      infiltrating immune cells. There was a trend toward decreased density of tumor
      infiltrating lymphocytes (TILs) within the group of relapsed cases. In addition,
      relapsed patients with codon 13 mutations had markedly lower levels of tumor
      infiltrating mature DC-LAMP(+) dendritic cells (DCs) and higher frequency of
      CD1a(+) cells compared with disease-free patients. Our data suggest that CRC
      patients with low levels of TILs, a high CD1a(+)/DC-LAMP(+) tumor-infiltrating DC
      ratio, and a KRAS mutation in codon 13 are at a high risk of disease recurrence.

PMID- 21884746
TI  - Identification of a new protective antigen of Bordetella pertussis.
AB  - Antigenic proteins whose expression is induced under iron starvation, an
      environmental condition that bacterial pathogens have to face during
      colonization, might be potential candidates for improved vaccine. By mean of
      immune proteomics we identified novel antigens of Bordetella pertussis maximally
      expressed under iron limitation. Among them, Bp1152 (named as IRP1-3) showed a
      particularly strong reaction with human IgG purified from pooled sera of
      pertussis-infected individuals. Computer analysis showed IRP1-3 as a dimeric
      membrane protein potentially involved in iron uptake. Experimental data revealed
      the surface-exposure of this protein and showed its increase under iron
      starvation to be independent of bacterial virulence phase. Immunization of mice
      with the recombinant IRP1-3 resulted in a strong antibody response. These
      antibodies not only recognized the native protein on bacterial surface but also
      promote effective bacterial phagocytosis by human PMN, a key protecting activity
      against this pathogen. Accordingly, IRP1-3 proved protective against B. pertussis
      infection in mouse model. Expression of IRP1-3 was found conserved among clinical
      isolates of B. pertussis and positively regulated by iron starvation in these
      strains. Taken together these results suggest that this protein might be an
      interesting novel vaccine candidate.

PMID- 21884747
TI  - Effectiveness of the pandemic H1N1 influenza vaccines against laboratory
      confirmed H1N1 infections: population-based case-control study.
AB  - BACKGROUND: Excellent immune responses following 1 or 2 doses of the monovalent
      inactivated pandemic H1N1 vaccines have been documented, but the effectiveness of
      these vaccines against laboratory-confirmed H1N1 infections in the general
      population is not clear. We evaluated the effectiveness of the pandemic H1N1 and
      seasonal trivalent influenza vaccines (TIV) used during the 2009 mass vaccination
      campaign in Manitoba (Canada) in preventing laboratory-confirmed H1N1 infections.
      METHODS: A population-based case-control study using data from Cadham Provincial
      Laboratory (CPL) and the Manitoba Immunization Monitoring System (MIMS). All
      Manitoba residents >=6 months of age who had a respiratory specimen tested at CPL
      for H1N1 were included in the study. Cases were individuals who tested positive
      for pandemic H1N1 influenza A by reverse transcriptase-PCR (N=1435). Controls
      were individuals who tested negative for both influenza A and B (N=2309).
      Information on receipt of TIV or H1N1 vaccine was obtained by record linkage with
      MIMS, the population-based province-wide immunization registry. RESULTS: Overall,
      the adjuvanted H1N1 vaccine was 86% (95%CI 75-93%) effective in preventing
      laboratory-confirmed H1N1 infections when vaccination occurred >=14 days before
      testing. Effectiveness seemed lower among older (>=50 years) individuals [51% (
      51 to 84%)] and among those with immunocompromising conditions [67% (-13 to
      90%)]. There was also evidence that the H1N1 vaccine might be less effective
      among those who had received the 2009/10 TIV. DISCUSSION: The adjuvanted H1N1
      vaccine used during Manitoba's H1N1 mass vaccination campaign was highly
      effective against laboratory-confirmed pandemic H1N1 infection, especially among
      children and younger adults.

PMID- 21884748
TI  - Antiradical and antioxidant activities of new bio-antioxidants.
AB  - Antioxidants could be promising agents for management of oxidative stress-related
      diseases. New biologically active compounds, belonging to a rare class of natural
      lignans with antiangiogenic, antitumoral and DNA intercalating properties, have
      been recently synthesized. These compounds are benzo[kl]xanthene lignans (1,2)
      and dihydrobenzofuran neolignans (3,4). The radical scavenging and chain-breaking
      antioxidant activities of compounds 1-4 were studied by applying different
      methods: radical scavenging activity by DPPH rapid test, chain-breaking
      antioxidant activity and quantum chemical calculations. All studied compounds
      were found to be active as DPPH scavengers but reaction time with DPPH and
      compounds' concentrations influenced deeply the evaluation. The highest values of
      radical scavenging activity (%RSAmax) and largest rate constants for reaction
      with DPPH were obtained for compounds 2 and 3. Comparison of %RSAmax with that of
      standard antioxidants DL-alpha-tocopherol (TOH), caffeic acid (CA) and butylated
      hydroxyl toluene (BHT) give the following new order of %RSA max: TOH (61.1%) > CA
      (58.6%) > 3 (36.3%) > 2 (28.1%) > 4 (6.7%) > 1 (3.6%) = BHT (3.6%). Chain
      breaking antioxidant activities of individual compounds (0.1-1.0 mM) and of their
      equimolar binary mixtures (0.1 mM) with TOH were determined from the kinetic
      curves of lipid autoxidation at 80  degrees C. On the basis of a comparable
      kinetic analysis with standard antioxidants a new order of the antioxidant
      efficiency (i.e., protection factor, PF) of compounds 1-4 were obtained: 2 (7.2)
      >= TOH (7.0) >= CA (6.7) > 1 (3.1) > 3 (2.2) > ferulic acid FA (1.5) > 4 (0.6);
      and of the antioxidant reactivity (i.e. inhibition degree, ID): 2 (44.0) >> TOH
      (18.7) >> CA (9.3) >> 1 (8.4) > 3 (2.8) > FA (1.0) > 4 (0.9). The important role
      of the catecholic structure in these compounds, which is responsible for the high
      chain-breaking antioxidant activity, is discussed and a reaction mechanism is
      proposed. Higher oxidation stability of the lipid substrate was found in the
      presence of equimolar binary mixtures 2 + TOH, 3 + TOH and 4 + TOH. However, an
      actual synergism was only obtained for the binary mixtures with compounds 3 and
      4. The geometries of compounds and all possible phenoxyl radicals were optimized
      using density functional theory. For description of the scavenging activity bond
      dissociation enthalpies (BDE), HOMO energies and spin densities were employed.
      The best correlation between theoretical and experimental data was obtained for
      compound 2, with the highest activity, and for compound 4 with the lowest
      activity. The BDE is the most important theoretical descriptor, which correlates
      with the experimentally obtained antioxidant activity of the studied
      benzo[kl]xanthene lignans and dihydrobenzofuran neolignans.

PMID- 21884749
TI  - Identifying three-way DNA junction-specific small-molecules.
AB  - Three-way junction DNA (TWJ-DNA, also known as 3WJ-DNA) is an alternative
      secondary DNA structure comprised of three duplex-DNAs that converge towards a
      single point, termed the branch point. This point is characterized by unique
      geometrical properties that make its specific targeting by synthetic small
      molecules possible. Such a targeting has already been demonstrated in the solid
      state but not thoroughly biophysically investigated in solution. Herein, a set of
      simple biophysical assays has been developed to identify TWJ-specific small
      molecule ligands; these assays, inspired by the considerable body of work that
      has been reported to characterize the interactions between small-molecules and
      other higher-order DNA (notably quadruplex-DNA), have been calibrated with a
      known non-specific DNA binder (the porphyrin TMPyP4) and validated via the study
      of a small series of triazacyclononane (TACN) derivatives (metal-free or not) and
      the identification of a fairly-affinic and exquisitely TWJ-selective candidate (a
      TACN-quinoline construct named TACN-Q).

PMID- 21884751
TI  - Mindfulness-based cognitive therapy (MBCT), cognitive style, and the temporal
      dynamics of frontal EEG alpha asymmetry in recurrently depressed patients.
AB  - Mindfulness-based cognitive therapy (MBCT), a meditation-based maintenance
      therapy, reduces the relapse risk in individuals suffering from major depressive
      disorder (MDD). However, only a few studies investigated the psychophysiological
      mechanisms underlying this protective effect. We examined effects of MBCT on
      trait rumination and mindfulness, as indicators of global cognitive style, as
      well as on residual depressive symptoms in a group of recurrently depressed
      patients (n=78) in remission. Additionally, alpha asymmetry in resting-state
      electroencephalogram (EEG) was assessed. Alpha asymmetry has been found to be
      predictive of affective style and a pattern indicative of stronger relative right
      hemispheric anterior cortical activity may represent a trait marker for the
      vulnerability to develop MDD. In line with previous findings, residual depressive
      symptoms and trait rumination decreased, whereas trait mindfulness increased
      following MBCT, while no such changes took place in a wait-list control group.
      Mean values of alpha asymmetry, on the other hand, remained unaffected by
      training, and shifted systematically toward a pattern indicative of stronger
      relative right-hemispheric anterior cortical activity in the whole sample. These
      findings provide further support for the protective effect of MBCT. In the
      examined patients who were at an extremely high risk for relapse, however, this
      effect did not manifest itself on a neurophysiological level in terms of alpha
      asymmetry, where a shift, putatively indicative of increased vulnerability, was
      observed.

PMID- 21884750
TI  - Cortical inhibition in alexithymic patients with borderline personality disorder.
AB  - High levels of alexithymia, a personality trait closely associated with emotion
      dysregulation, have been found in several psychiatric disorders including
      borderline personality disorder (BPD). Both BPD and alexithymia have been related
      to impaired cortical inhibition; however, this relationship has not been tested
      directly. The aim of the present study was, therefore, to investigate whether
      cortical inhibition is modulated by alexithymia in BPD. Fifteen BPD patients with
      Toronto-Alexithymia Scale (TAS-20) scores >=61, 14 BPD patients with TAS-20 <61,
      and 16 healthy controls were examined using different TMS paradigms. High
      alexithymia patients showed a shortened cortical silent period (CSP) compared to
      low-alexithymia patients and controls. Additionally, a significant inverse
      correlation was found between the TAS-20, the left CSP and the left transcallosal
      conduction time. These findings indicate that alexithymia is associated with
      changes in GABAergic neurotransmission and facilitated transcallosal inhibition.
      The results highlight the importance of considering alexithymia in BPD.

PMID- 21884752
TI  - Striatal expression of Homer1a is affected by genotype but not dystonic phenotype
      of tottering mice: a model of spontaneously occurring motor disturbances.
AB  - Tottering (tg) mice carry a missense mutation in the gene coding for P/Q-type
      voltage-dependent Ca(2+) channels (VDCCs). Aberrant functioning of P/Q-type VDCCs
      results in molecular alterations in Ca(2+) currents and in glutamate and dopamine
      systems. As a consequence, tottering mice exhibit mild ataxia, spontaneous
      epilepsy, and paroxysmal dyskinesia. In this study, we evaluated whether the
      tottering mice genotype (homozygous vs. heterozygous) and abnormal movement
      phenotype (mice exhibiting paroxysmal dyskinesia vs. mice not exhibiting
      dyskinesia) may affect the expression of Homer1a. Homer1a is a gene whose
      expression is modulated by glutamate, dopamine and Ca(2+) concentrations. Over
      expression of Homer1a has been described in epilepsy and motor dysfunctions.
      Thereby, changes in Homer1a expression could take place in tottering mice.
      Studying the expression profile of this gene may shed light on the molecular
      events occurring in tottering mice. Moreover, tottering mice may represent a
      valuable animal model for investigating Homer1a involvement in motor disorders.
      Homer1a expression was decreased in all striatal subregions, with the exclusion
      of the dorsolateral caudate-putamen, in heterozygous mice compared to wild-type
      and homozygous mice. Gene expression was decreased in the core of the accumbens
      in mice exhibiting paroxysmal dyskinesia compared to wild-type mice and to mice
      not exhibiting dyskinesia. These results demonstrate that the tottering mouse
      genotype may affect striatal expression of Homer1a, possibly as a result of
      imbalance between Ca(2+) channels subtypes or Ca(2+)-related molecules in
      heterozygous vs. homozygous mice.

PMID- 21884753
TI  - Association between prior alcohol use disorders and decreased prefrontal gray
      matter volumes in bipolar I disorder patients.
AB  - Up to 50% of bipolar disorder (BD) patients present a lifetime diagnosis of
      alcohol use disorders (AUD). BD patients with comorbid AUD, even when in
      remission from the AUD, have a poorer outcome and functional impairment than
      patients with BD alone. The neurobiological abnormalities that potentially
      characterize this severe subgroup of BD patients are unknown. Our goal was to
      investigate gray matter (GM) volume abnormalities in BD I patients with comorbid
      AUD. Twenty-one BD-AUD patients, 21 BD-nonAUD BD patients, and 25 healthy
      controls (HC), matched by age, gender, and handedness were studied. The BD-AUD
      patients were in remission from AUD on average for 6.8 years. 3D SPGR MRIs (TR=25
      ms, TE=5 ms, slice thickness=1.5 mm) were acquired from all subjects using a 1.5
      T GE Signa Imaging System. We used an optimized voxel-based morphometry protocol
      to compare GM volumes among the groups. BD-AUD patients presented smaller GM
      volumes in the left medial frontal and the right anterior cingulate gyri compared
      to BD-nonAUD patients. BDnon-AUD patients did not present GM volume differences
      compared to HC. These findings provide evidence for an effect of comorbid AUD on
      regional brain structure of BD I patients and warrant further research on
      neurobiological aspects of this prevalent and severe comorbidity.

PMID- 21884754
TI  - Impairment of odor recognition and odor-induced emotions in type 1 myotonic
      dystrophy.
AB  - This study aimed to test whether type 1 myotonic dystrophy (DM1) patients who
      have a lower sensitivity to emotional facial expressions have an abnormal
      olfactory threshold or recognition level. We measured DM1 patients' performances
      in an olfactory acuity test and respiratory responses to odor stimuli, and
      compared their results to those of healthy controls (HCs). We found that DM1
      patients exhibited a significantly reduced odor detection sensitivity compared
      with that in HCs. Three out of seven DM1 patients exhibited impaired odor
      recognition, while other four patients had significantly lower odor recognition
      compared with HCs. Even when patients were able to identify the type of odor, the
      levels of pleasantness they reported experiencing in response to a pleasant odor
      were significantly lower than those reported by HCs. These subjective data in DM1
      patients were reflected in the respiratory responses (RRs). In the current study,
      one patient showed impairments in both odor detection and odor recognition.
      Abnormalities of the olfactory limbic areas might have been the cause of the
      olfactory impairments observed in the DM1 patients.

PMID- 21884756
TI  - Dopamine oxidation facilitates rotenone-dependent potentiation of N-methyl-D
      aspartate currents in rat substantia nigra dopamine neurons.
AB  - Rotenone is a mitochondrial poison that causes dopamine cell death and is used as
      a model of Parkinson's disease in rodents. Recently, we showed that rotenone
      augments currents evoked by N-methyl-D-aspartate (NMDA) by relieving voltage
      dependent Mg(2+) block in rat substantia nigra compacta (SNC) dopamine neurons.
      Because rotenone is well known to generate reactive oxygen species (ROS), we
      conducted the present experiments to evaluate the role of ROS in mediating the
      effect of rotenone on NMDA current augmentation. Using patch pipettes to record
      whole-cell currents from SNC neurons in slices of rat brain, we found that the
      ability of rotenone (100 nM) to increase NMDA (3-30 MUM) current was antagonized
      by the antioxidant agent n-acetylcysteine (1 mM). In contrast, mercaptosuccinate
      (1 mM), which blocks glutathione peroxidase and raises tissue levels of H(2)O(2),
      mimicked rotenone by augmenting inward currents evoked by NMDA. Because oxidation
      of dopamine can also generate ROS, we explored the role of dopamine on this
      action of rotenone. We prepared dopamine-depleted midbrain slices from rats that
      had been pretreated with reserpine (5 mg/kg ip) and alpha-methyl-para-tyrosine
      (AMPT, 250 mg/kg ip). Dopamine depletion blocked the ability of rotenone (100 nM)
      to increase inward current evoked by NMDA (30 MUM). Rotenone-dependent
      augmentation of NMDA current was also blocked by the monoamine oxidase inhibitor
      pargyline (100 MUM) in slices prepared from normal rats. In contrast, the
      dopamine precursor levodopa potentiated the action of rotenone on NMDA current.
      These results suggest that ROS and/or dopamine oxidation products mediate the
      ability of rotenone to potentiate NMDA currents. Because excessive NMDA receptor
      stimulation can produce excitotoxicity, our results suggest that oxidative
      metabolism of dopamine might facilitate the neurotoxicity of rotenone.

PMID- 21884755
TI  - The role of calcium and mitochondrial oxidant stress in the loss of substantia
      nigra pars compacta dopaminergic neurons in Parkinson's disease.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disease in
      developed countries. The core motor symptoms are attributable to the degeneration
      of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc). Why
      these neurons succumb in PD is not clear. One potential clue has come from the
      observation that the engagement of L-type Ca2+ channels during autonomous
      pacemaking elevates the sensitivity of SNc DA neurons to mitochondrial toxins
      used to create animal models of PD, suggesting that Ca2+ entry is a factor in
      their selective vulnerability. Recent work has shown that this Ca2+ entry also
      elevates mitochondrial oxidant stress and that this stress is exacerbated by
      deletion of DJ-1, a gene associated with an early onset, recessive form of PD.
      Epidemiological data also support a linkage between L-type Ca2+ channels and the
      risk of developing PD. This review examines the hypothesis that the primary
      factor driving neurodegenerative changes in PD is the metabolic stress created by
      Ca2+ entry, particularly in the face of genetic or environmental factors that
      compromise oxidative defenses or proteostatic competence.

PMID- 21884757
TI  - Slow phasic changes in nucleus accumbens dopamine release during fixed ratio
      acquisition: a microdialysis study.
AB  - Nucleus accumbens dopamine (DA) is a critical component of the brain circuitry
      regulating behavioral output during reinforcement-seeking behavior. Several
      studies have investigated the characteristics of accumbens DA release during the
      performance of well-learned operant behaviors, but relatively few have focused on
      the initial acquisition of particular instrumental behaviors or operant
      schedules. The present experiments focused on the initial acquisition of operant
      performance on a reinforcement schedule by studying the transition from a fixed
      ratio 1 (FR1) schedule to another operant schedule with a higher ratio
      requirement (i.e. fixed ratio 5 [FR5]). Microdialysis sessions were conducted in
      different groups of rats that were tested on either the FR1 schedule; the first,
      second, or third day of FR5 training; or after weeks of FR5 training. Consistent
      with previous studies, well-trained rats performing on the FR5 schedule after
      weeks of training showed significant increases in extracellular DA in both core
      and shell subregions of nucleus accumbens during the behavioral session. On the
      first day of FR5 training, there was a substantial increase in DA release in
      nucleus accumbens shell (i.e. approximately 300% of baseline). In contrast,
      accumbens core DA release was greatest on the second day of FR5 training. In
      parallel experiments, DA release in core and shell subregions did not
      significantly increase during free consumption of the same high carbohydrate food
      pellets that were used in the operant experiments, despite the very high levels
      of food intake in experienced rats. However, in rats exposed to the high
      carbohydrate food for the first time, there was a tendency for extracellular DA
      to show a small increase. These results demonstrate that transient increases in
      accumbens DA release occur during the initial acquisition of ratio performance,
      and suggest that core and shell subregions show different temporal patterns
      during acquisition of instrumental behavior.

PMID- 21884759
TI  - Keeping an eye on imagery: the role of eye movements during motor imagery
      training.
AB  - We recently found that spontaneous eye movements occur during motor imagery of
      hand movements, which are similar to those made during physical execution. In
      physical execution, eye movements have been shown to play an important role
      during training. In motor imagery practice, however, their effect remains
      unclear. Therefore, in the present study, we examined the role of eye movements
      during motor imagery practice with specific interest in the impact of task
      complexity and effector specificity. Thirty-six young healthy participants were
      tested before and after 4 days of visual motor imagery training on a Virtual
      Radial Fitts' task with different indices of difficulty. Training was performed
      with the nondominant hand only. Subjects were divided into a group that trained
      while spontaneous eye movements were allowed, one that kept the eyes fixed during
      training, and a control group. Electro-oculography and electromyography signals
      were monitored to guarantee task compliance during imagery. The results indicated
      that eye movements during imagery did not affect the temporal parameters of the
      trained movement. They did, however, help to achieve maximal gains in movement
      accuracy and efficiency. These positive effects on the spatial parameters were
      most pronounced during conditions with high accuracy demands and were present for
      both the trained and the untrained hand. These findings contribute to guidelines
      for optimizing training protocols based on motor imagery.

PMID- 21884758
TI  - Aging-related alterations in orexin/hypocretin modulation of septo-hippocampal
      amino acid neurotransmission.
AB  - GABAergic neurons of the medial septum of the basal forebrain make up a
      substantial portion of the septo-hippocampal pathway fibers, and are known to
      modulate hippocampal amino acid neurotransmission and support cognitive function.
      Importantly, these neurons are also implicated in age-related cognitive decline.
      Hypothalamic orexin/hypocretin neurons innervate and modulate the activity of
      these basal forebrain neurons and also provide direct inputs to the hippocampus.
      However, the precise role of orexin inputs in modulating hippocampal amino acid
      neurotransmission--as well as how these interactions are altered in aging--has
      not been defined. Here, orexin A (OxA) was administered to CA1 and the medial
      septum of young (3-4 months) and aged (27-29 months) Fisher 344 Brown Norway
      rats, and hippocampal GABA and glutamate efflux was analyzed by in vivo
      microdialysis. Following CA1 infusion of OxA, extracellular GABA and glutamate
      efflux was increased, but the magnitude of orexin-mediated efflux was not altered
      as a function of age. However, medial septum infusion of OxA did not impact
      hippocampal efflux in young rats, while aged rats exhibited a significant
      enhancement in GABA and glutamate efflux compared to young counterparts.
      Furthermore, immunohistochemical characterization of the medial septum revealed a
      significant decrease in parvalbumin (PV)-positive cell bodies in aged animals,
      and a significant reduction in orexin fiber innervation to the remaining
      GABAergic cells within the septum, while orexin innervation to the hippocampus
      was unaltered by the aging process. These findings indicate that: (1) OxA
      directly modulates hippocampal amino acid neurotransmission in young animals, (2)
      Aged animals show enhanced responsivity to exogenous OxA activation of the septo
      hippocampal pathway, and (3) Aged animals undergo an intrinsic reduction in
      medial septum PV-immunoreactivity and a decrease in orexin innervation to
      remaining septal PV neurons. Alterations in orexin regulation of septo
      hippocampal activity may contribute to age-related dysfunctions in arousal,
      learning, and memory.

PMID- 21884760
TI  - Exploring the role of the substantia nigra pars reticulata in eye movements.
AB  - Experiments that demonstrated a role for the substantia nigra in eye movements
      have played an important role in our understanding of the function of the basal
      ganglia in behavior more broadly. In this review we explore more recent
      experiments that extend the role of the substantia nigra pars reticulata from a
      simple gate for eye movements to include a role in cognitive processes for eye
      movements. We review recent evidence suggesting that basal ganglia nuclei beyond
      the substantia nigra may also play a role in eye movements and the cognitive
      events leading up to the production of eye movements. We close by pointing out
      some unresolved questions in our understanding of the relationship of basal
      ganglia nuclei and eye movements.

PMID- 21884761
TI  - Endocannabinoid signaling in the amygdala: anatomy, synaptic signaling, behavior,
      and adaptations to stress.
AB  - The molecular constituents of endocannabinoid (eCB) signaling are abundantly
      expressed within the mammalian amygdaloid complex, consistent with the robust
      role of eCB signaling in the modulation of emotional behavior, learning, and
      stress-response physiology. Here, we detail the anatomical distribution of eCB
      signaling machinery in the amygdala and the role of this system in the modulation
      of excitatory and inhibitory neuroplasticity in this region. We also summarize
      recent findings demonstrating dynamic alternations in eCB signaling that occur in
      response to stress exposure, as well as known behavioral consequences of eCB
      mediated modulation of amygdala function. Finally, we discuss how integrating
      anatomical and physiological data regarding eCB signaling in the amygdala could
      help elucidate common functional motifs of this system in relation to broader
      forebrain function.

PMID- 21884762
TI  - Glutamate and nicotinic receptor interactions in working memory: importance for
      the cognitive impairment of schizophrenia.
AB  - This article reaches across disciplines to correlate results in molecular,
      cellular, behavioral, and clinical research to develop a more complete picture of
      how working memory (WM) functions. It identifies a new idea that deserves further
      investigation. NMDA glutamate receptors (NMDAR) are critical for memory function.
      NMDAR inhibition effectively reproduces principal manifestations of schizophrenia
      (SP), such as WM impairment and GABAergic deficit (mainly reduction of glutamic
      acid decarboxylase 67 (GAD67) and parvalbumin (PV) content). Nicotine and
      selective alpha7 nicotinic acetylcholine receptor (nAChR) agonists reduce WM
      impairments in patients with SP and reverse WM deficits in animals treated with
      NMDAR antagonists. The mechanism of this effect is unknown. Importantly, WM
      recovery occurs even before restoration of NMDAR blockade-induced molecular
      alterations, including reduced GAD67 in interneurons. Our insight into the
      cognitive-enhancing effect of alpha7 nAChR agonists, particularly in the animal
      models of SP, combines reviews of recent findings on glutamate and nicotinic
      receptor expression in the neuronal circuits involved in WM, the properties of
      these receptors, their implication in WM regulation, generation of rhythmic
      neuronal activity, resulting in a proposed hypothesis for further investigations.
      We suggest that (1) cortical/hippocampal interneurons, particularly PV positive,
      play a crucial role in WM and that impairment of these cells in SP could be
      behind the WM deficit; (2) activation of alpha7 nAChRs could restore calcium
      signaling and intrinsic properties of these interneurons, and associated with
      these events, computational capacity, gamma rhythmic activity, and WM would also
      be restored.

PMID- 21884763
TI  - Gap junctions contribute to astrocytic resistance against zinc toxicity.
AB  - Astrocytic gap junctions have been implicated in the regulation of cell
      viability. High amounts of extracellular zinc, which is released during ischemia,
      seizure, and brain trauma, can be cytotoxic to astrocytes. We tested whether gap
      junction coupling between astrocytes plays an important role in modulating zinc
      toxicity in hippocampal astrocytes. Zinc induces cell death in a dose-dependent
      manner in primary cultured hippocampal astrocytes. Two gap junction inhibitors,
      18beta-glycyrrhetinic acid and arachidonic acid, had no effect on zinc-induced
      cell death in low-confluence culture, where physical separation prevents gap
      junctions from forming. However, these inhibitors can potentiate zinc toxicity in
      high-confluence astrocyte cultures. Zinc toxicity was substantially suppressed
      upon connexin 43 overexpression, whereas knockdown caused a significant
      enhancement of the toxicity in high-confluence cultures. These data suggest that
      gap junctions in hippocampal astrocytes provide a protective role against zinc
      toxicity.

PMID- 21884764
TI  - "Anticipated" nucleosome positioning pattern in prokaryotes.
AB  - Linguistic (word count) analysis of prokaryotic genome sequences, by Shannon N
      gram extension, reveals that the dominant hidden motifs in A+T rich genomes are
      T(A)(T)A and G(A)(T)C with uncertain number of repeating A and T. Since
      prokaryotic sequences are largely protein-coding, the motifs would correspond to
      amphipathic alpha-helices with alternating lysine and phenylalanine as
      preferential polar and non-polar residues. The motifs are also known in
      eukaryotes, as nucleosome positioning patterns. Their existence in prokaryotes as
      well may serve for binding of histone-like proteins to DNA. In this case the
      above patterns in prokaryotes may be considered as "anticipated" nucleosome
      positioning patterns which, quite likely, existed in prokaryotic genomes before
      the evolutionary separation between eukaryotes and prokaryotes.

PMID- 21884765
TI  - Synthesis of azoxystrobin transformation products and selection of monoclonal
      antibodies for immunoassay development.
AB  - The use of agrochemicals for crop protection may result in the presence of toxic
      residues in soils and aquatic environments, besides in foodstuffs. Most often
      just the parent compound is included in the definition of pesticide residue, even
      though chemicals resulting from biotransformation and degradation routes might
      also be of toxicological relevance. Azoxystrobin is a broad-spectrum systemic
      fungicide widely used worldwide to combat pathogenic fungi affecting plants. We
      herein report the synthesis and detailed chemical characterization of several of
      the most relevant metabolites and degradates of azoxystrobin. These compounds
      were further employed as ligands for screening a collection of monoclonal
      antibodies to azoxystrobin, which had been previously generated from haptens
      functionalized at different positions of the target chemical. As a result, an
      antibody was identified capable of binding, with subnanomolar affinity, not only
      azoxystrobin but also its main transformation products, such as the so-called
      acid and enol derivatives, as well as the azoxystrobin (Z)-isomer. The selected
      binder was demonstrated as a useful immunoreagent for the development of
      immunochemical assays as novel analytical tools for the qualitative determination
      of azoxystrobin and its metabolites and degradates.

PMID- 21884766
TI  - Rat hyperactivity by bisphenol A, but not by its derivatives, 3-hydroxybisphenol
      A or bisphenol A 3,4-quinone.
AB  - Detoxification in the central nervous system is largely unknown. The mechanism of
      neurotoxicity of bisphenol A, a toxic environmental chemical remains obscure. We
      examined the effects of bisphenol A, and its derivatives, 3-hydroxybisphenol A
      and bisphenol A 3,4-quinone on rat behavior as possible metabolites of bisphenol
      A. A single intracisternal administration of bisphenol A (20 MUg equivalent to 87
      nmol) into 5-day-old male Wistar rats caused significant hyperactivity at 4-5
      weeks of age. It was about 1.3 fold more active in the nocturnal phase than
      control rats. However, neither 3-hydroxybisphenol A nor bisphenol A 3,4-quinone
      at the same amount (87 nmol) increased the spontaneous motor activity. Gas
      chromatographic-mass spectrometric (GC-MS) analyses of the treated brain revealed
      that 7% of the parent chemical resided in the brain at 8 weeks of age, but its
      derivatives were not found. This suggested a difference in metabolic turnover of
      these compounds or a difference in their stabilities. We conclude that bisphenol
      A per se caused hyperactivity in the rat, eliminating the possibility that
      possible metabolic forms of bisphenol A, 3-hydroxybisphenol A and bisphenol A 3,4
      quinone have the ability to elicit rat hyperactivity, probably because of longer
      lasting residence of the parent compound in the brain.

PMID- 21884767
TI  - Enhanced cellular delivery of idarubicin by surface modification of propyl starch
      nanoparticles employing pteroic acid conjugated polyvinyl alcohol.
AB  - Enhanced intracellular internalization of the anti-cancer active idarubicin (IDA)
      was achieved through appropriate surface modification of IDA loaded propyl starch
      nanoparticles. This was conducted by synthesizing pteroic acid modified polyvinyl
      alcohol (ptPVA) and employing this stabilizer for formulating the said
      nanoparticles. Pteroic acid attached at the nanoparticles improved the surface
      protein adsorption of the nanoparticle, a condition which the nanoparticles would
      largely experience in vitro and in vivo and hence improve their cellular
      internalization. Spherical, homogenous IDA nanoparticles (214 +/- 5 nm) with
      surface modified by ptPVA were formulated using the solvent emulsification
      diffusion technique. The encapsulation efficiency and drug loading amounted
      around 85%. In vitro release studies indicated a controlled release of IDA.
      Safety and efficacy of the nanoparticles was confirmed by suitable cellular
      cytotoxicity assays. Protein binding studies indicated a higher adsorption of the
      model protein on nanoparticles formulated with ptPVA as compared to PVA. Cellular
      uptake studies by confocal laser scanning microscopy revealed a higher cellular
      uptake of ptPVA stabilized nanoparticles thus confirming the proposed hypothesis
      of higher protein adsorption being responsible for higher cellular
      internalization.

PMID- 21884768
TI  - Lutein nanocrystals as antioxidant formulation for oral and dermal delivery.
AB  - Lutein is a well known antioxidant and anti-free radical used in cosmetic,
      nutraceutical industry with potential application in pharmaceutics as supportive
      antioxidant in treatments. As lipophilic molecule it is poorly soluble in water
      and has a low bioavailability. Lutein nanosuspension was prepared to enhance
      dissolution velocity, saturation solubility (C(s)), which are major factors
      determining oral bioavailability and penetration into the skin. High pressure
      homogenization (HPH) was used to prepare lutein nanosuspension. Particle size was
      determined by photon correlation spectroscopy (PCS) and laser diffractometry
      (LD). The lowest PCS diameter obtained was about 429 nm, the LD diameter 90% of
      1.2 MUm. The zeta potential was about -40 mV in water and -17 mV in the original
      dispersion medium. The 3 month storage study at different temperatures (4 degrees
      C, 25 degrees C, 40 degrees C) confirmed physical stability despite the low zeta
      potential of -17 mV in original surfactant solution. A pronounced increase in
      saturation solubility by 26.3 fold was obtained for lutein nanocrystals compared
      to coarse powder. The lutein nanosuspension was converted into pellets and filled
      into hard gelatin capsules for nutraceutical use, showed a superior in vitro
      release (factor of 3-4). Lyophilized nanosuspension was prepared for subsequent
      incorporation into creams and gels. The lyophilized nanosuspension was very well
      re-dispersible (435 nm). Using cellulose nitrate membranes as in vitro model,
      permeation through this barrier was 14* higher for lutein nanocrystals compared
      to coarse powder. However, pig ear skin did not allow lutein to permeate but
      supported localization of the lutein in the skin where it should act anti
      oxidatively.

PMID- 21884769
TI  - Process induced transformations during tablet manufacturing: phase transition
      analysis of caffeine using DSC and low frequency micro-Raman spectroscopy.
AB  - The phase transition of a model API, caffeine Form I, was studied during
      tableting process monitored with an instrumented press. The formulation used had
      a plastic flow behavior according to the Heckel model in the compression pressure
      range of 70-170 MPa. The quantitative methods of analysis used were Differential
      Scanning Calorimetry (DSC) and low frequency Micro Raman Spectroscopy (MRS) which
      was used for the first time for the mapping of polymorphs in tablets. They
      brought complementary contributions since MRS is a microscopic spectral analysis
      with a spatial resolution of 5 MUm(3) and DSC takes into account a macroscopic
      fraction (10mg) of the tablet. Phase transitions were present at the surfaces,
      borders and center of the tablets. Whatever the pressure applied during the
      compression process, the transition degree of caffeine Form I toward Form II was
      almost constant. MRS provided higher transition degrees (50-60%) than DSC (20
      35%). MRS revealed that caffeine Form I particles were partially transformed in
      all parts of the tablets at a microscopic scale. Moreover, tablet surfaces showed
      local higher transition degree compared to the other parts.

PMID- 21884770
TI  - Self-nanoemulsifying drug delivery system of persimmon leaf extract: Optimization
      and bioavailability studies.
AB  - In current study, a self-nanoemulsifying drug delivery system (SNEDDS) of
      persimmon (Diospyros kaki) leaf extract (PLE) was developed and characterized to
      compare its in vitro dissolution and relative bioavailability with commercially
      available tablets (Naoxinqing tablets). Pseudo-ternary phase diagrams were
      constructed by phase diagram by micro plate dilution (PDMPD) method, of which the
      evaluation method was improved to use Multiskan Ascent for identifying turbidity.
      The formulation of PLE-loaded SNEDDS was optimized by an extreme vertices
      experimental design. The optimized nanoemulsion formulation, loading with 44.48
      mg/g PLE total flavonoids, consisted of Cremophor EL, Transcutol P, Labrafil M
      1944 CS (56:34:10, w/w), and it remained stable after storing at 40 degrees C, 25
      degrees C, 4 degrees C for at least 6 months. When diluted with water, the SNEDDS
      droplet size was 34.85 nm and the zeta potential was -6.18 mV. Compared with the
      commercial tablets, the AUC of both quercetin and kaempferol, which are
      representative active flavonoids of PLE, was increased by 1.5-fold and 1.6-fold
      respectively following oral administration of PLE-loaded SNEDDS in fasting beagle
      dogs. These results indicate that SNEDDS is a promising drug delivery system for
      increasing the oral bioavailability of PLE.

PMID- 21884771
TI  - Formulation design for poorly water-soluble drugs based on biopharmaceutics
      classification system: basic approaches and practical applications.
AB  - The poor oral bioavailability arising from poor aqueous solubility should make
      drug research and development more difficult. Various approaches have been
      developed with a focus on enhancement of the solubility, dissolution rate, and
      oral bioavailability of poorly water-soluble drugs. To complete development works
      within a limited amount of time, the establishment of a suitable formulation
      strategy should be a key consideration for the pharmaceutical development of
      poorly water-soluble drugs. In this article, viable formulation options are
      reviewed on the basis of the biopharmaceutics classification system of drug
      substances. The article describes the basic approaches for poorly water-soluble
      drugs, such as crystal modification, micronization, amorphization, self
      emulsification, cyclodextrin complexation, and pH modification. Literature-based
      examples of the formulation options for poorly water-soluble compounds and their
      practical application to marketed products are also provided. Classification of
      drug candidates based on their biopharmaceutical properties can provide an
      indication of the difficulty of drug development works. A better understanding of
      the physicochemical and biopharmaceutical properties of drug substances and the
      limitations of each delivery option should lead to efficient formulation
      development for poorly water-soluble drugs.

PMID- 21884772
TI  - Evaluation of the physical and biological properties of hyaluronan and hyaluronan
      fragments.
AB  - Hyaluronan (HA) has been extensively used for various medical applications,
      including osteoarthritis, tissue augmentation and ocular surgery. More recently,
      it has been investigated for use in polymer therapeutics as a carrier for drugs
      and biologically active proteins, thanks to its biodegradability,
      biocompatibility and inherent biological properties. Such biological functions
      are strongly dependent on HA's chain length, yet the molecular weight of HAs used
      in polymer conjugates varies widely and is inconsistent with its intended
      application. Therefore, this study aimed to determine the ideal chain length of
      HA to be used in polymer conjugates for enhanced tissue repair. HA fragments
      (M(w) 45,000-900,000g/mol) were prepared by acid hydrolysis of rooster comb HA
      and their physicochemical and biological properties were characterized. Such HA
      fragments had a highly extended, almost rod-like solution conformation and
      demonstrated chain length- and concentration-dependent viscosity, while exposure
      to HAase caused a rapid reduction in HA viscosity, which was most significant for
      the native HA. Initial HA hydrolysis rate by HAase varied strongly with HA chain
      length and was dependent on the formation of a stable enzyme-substrate complex.
      When normal human dermal fibroblasts were exposed to the different HA fragments
      for 72h, only native (900,000g/mol) HA reduced proliferation at 1000MUg/mL.
      Conversely, only the smallest HA fragment (70,000g/mol) reduced the proliferation
      of chronic wound fibroblasts, at 1000MUg/mL. The 70,000g/mol HA fragment also
      promoted the greatest cell attachment. These observations demonstrate that low
      molecular weight (70,000-120,000g/mol) HA fragments would be best suited for the
      delivery of proteins and peptides with applications in chronic wound healing and
      paves the way for the rationalized development of novel HA conjugates.

PMID- 21884773
TI  - A comparative study on the tissue distributions of rhubarb anthraquinones in
      normal and CCl4-injured rats orally administered rhubarb extract.
AB  - AIM OF THE STUDY: The present study comparatively investigated the tissue
      distributions of rhubarb anthraquinone derivatives (AQs) to examine whether they
      undergo different uptakes in normal or CCl(4)-induced liver-damaged rats, to
      explore possible reasons for the different toxicities of AQs in pathological
      model rats and normal rats at the tissue distribution level. MATERIALS AND
      METHODS: The total rhubarb extract (14.49 g kg(-1) of body weight per day based
      on the quantity of crude material) was administrated orally to normal and model
      rats for 12 weeks. The concentrations of free AQs in tissues were quantitated by
      liquid chromatography-tandem mass spectrometry (LC-MS). After drug withdrawal for
      4 weeks, tissue distributions were again determined. RESULTS: The five free AQs
      aloe-emodin, rhein, emodin, chrysophanol and physcion--were detected in the
      liver, kidney and spleen, while only rhein, aloe-emodin and emodin reached the
      quantitative limit. The tissue distributions of rhein (p < 0.001), aloe-emodin (p
      < 0.001) and emodin (p < 0.05) in normal rats were higher than those in model
      rats with rhein>aloe-emodin>emodin in kidney and spleen tissues and aloe-emodin >
      rhein > emodin in liver tissues. Free AQs were not detected in the tissues after
      drug withdrawal for 4 weeks. CONCLUSIONS: These results suggest that the tissue
      toxicity of AQs in normal animals is higher than that in pathological model
      animals with little accumulative toxicity of rhubarb. The results are concordant
      with the traditional Chinese theory of You Gu Wu Yun recorded first in Su Wen, a
      classical Chinese medical treatise.

PMID- 21884774
TI  - Effects of a Chinese traditional formula Kai Xin San (KXS) on chronic fatigue
      syndrome mice induced by forced wheel running.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: In traditional medicine, Kai Xin San (KXS),
      composed of ginseng (Panax ginseng), hoelen (Wolfiporia cocos), polygala
      (Polygala tenuifolia) and Acorus gramineus, is famous for the treatment of
      emotion-thought disease, such as settling fright, quieting the spirit and
      nourishing the heart. AIM OF THE STUDY: The present study investigated the effect
      of KXS on chronic fatigue syndrome (CFS) mice induced by forced wheel running.
      MATERIALS AND METHODS: Seventy two healthy adult male Kunming mice were randomly
      divided into six groups: home cage control group, CFS group, CFS group with
      Modafinil treatment at 13 mg/kg/d doge, KXS treatment at 175 mg/kg/d, 350 mg/kg/d
      and 700 mg/kg/d doge. CFS mice were induced by forced wheel running with higher
      speed for 4 weeks and then taken an exhausted exercise. The biochemical
      parameters including serum lactate dehydrogenase (LDH), serum urea nitrogen
      (SUN), serum testosterone (T), liver glycogen (LG), muscle glycogen (MG) and
      muscle lactic acid (MLA) were determined by using commercially available kits.
      The splenocytes proliferation from mice was examined by MTT method. The levels of
      interleukin-2 (IL-2) and interleukin-4 (IL-4) secreted by splenocytes were
      determined by ELISA. RESULTS: CFS mice with KXS administration exhibited less
      electric shock time when compared with CFS group without drug treatment. The
      effect of KXS has after demonstrated reduction in SUN, LDH and MLA levels and an
      increase in T, LG and MG levels. CFS mice with KXS could improve the
      proliferation of splenocytes compared with CFS group without drug treatment. The
      cultured splenocytes from CFS mice without KXS supplementation produced more
      interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared with home cage
      control mice. The cultured splenocytes of CFS mice with KXS supplementation
      produced more interleukin-2 (IL-2) but less interleukin-4 (IL-4) when compared
      with CFS group without drug treatment. CONCLUSIONS: The results of this
      preliminary study provide evidence that KXS could ameliorate CFS by affecting the
      physiological markers for fatigue. This study also supported the use of KXS
      against CFS by improving the proliferation of splenocytes from CFS mice and
      modulating the disturbance of cytokines induced by CFS.

PMID- 21884775
TI  - Evaluation of the acute dermal exposure of the ethanolic and hexanic extracts
      from leaves of Schinus molle var. areira L. in rats.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Schinus molle var. areira L. (Anacardiaceae) is
      employed in herbal medicine for many conditions, including respiratory, urinary
      and menstrual disorders, and as a digestive stimulant, diuretic, astringent and
      antidepressant. It is also known for its topical use as wound healer, antiseptic,
      for skin disorders and as repellent and insecticide. In the present work, the
      acute dermal exposure to ethanolic and hexanic extracts from leaves of Schinus
      molle var. areira was studied in rats. MATERIALS AND METHODS: A single dose of
      2000 mg/kg of body weight of ethanolic and hexanic extracts from leaves was
      applied on the shaved skin of male and female rats. After 24h of exposure, the
      patch was removed and any sign of irritation was recorded. Behavioral and
      functional parameters in a functional observational battery and motor activity in
      an open field were assessed after the exposure to the extracts. Then, after 14
      days of observation, animals were retested. Finally, histopathological studies
      were conducted on several organs. RESULTS: Slight signs of erythema and edema
      were observed in the skin site of exposure, but they disappeared after 48 h. The
      exposure to the hexanic extract produced an increase in parameters of activity,
      rearing and arousal assessed in the functional observational battery, which
      reversed after 14 days. On the other hand, the ethanolic extract caused an
      increase in locomotor activity, reflected in a higher number of rearings
      performed in the open field in the evaluation carried out on Day 14. No
      histopathological alterations were detected in the analyzed organs. CONCLUSIONS:
      The results show that the acute dermal exposure of the ethanolic and hexanic
      extracts from leaves of Schinus molle var. areira only causes a slight and
      reversible skin irritation, and a mild stimulatory effect in rats. All these
      indicate that the topical use of these extracts would be safe.

PMID- 21884776
TI  - Acute and subchronic oral toxicity assessment of the herbal formula Kai-Xin-San.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS) is a famous traditional Chinese
      medicine (TCM) formula. It has been used in the treatment of diseases including
      neurasthenia, Alzheimer's disease and neurosis. AIM OF THE STUDY: To provide
      information on the potential toxicity of KXS, we evaluated the acute and
      subchronic toxicity in rodents. MATERIALS AND METHODS: In acute study, a single
      administration of KXS was given orally to mice at doses ranging from 19.67 to
      60.04 g/kg. In the sub-chronic oral toxicity study, KXS was administered to rats
      at 0, 1, 3 and 9 g/kg for 13 weeks. Moreover, 30 days of post treatment
      (withdrawal study) was conducted. Mortalities, clinical signs, body weight
      changes, food and water consumption, haematological and biochemical parameters,
      gross findings and organ weights were monitored during the study period. RESULTS:
      In the sub-chronic study in rats, daily oral administration of KXS at the dose of
      9 g/kg/day result in significant increase in WBC, lymphocyte, alkaline
      phosphatase, blood sugar and significant decrease in bodyweight, serum Cre, CK
      and CHO at the last week of treatment. Recovery except for the body weight was
      observed after 30 days of post treatment. CONCLUSIONS: KXS is relatively safe for
      oral medication. The LD(50) of KXS was over 32.59 g/kg for mice. The no-observed
      adverse-effect-level (NOAEL) was considered to be 19.67 g/kg/day for rats.

PMID- 21884777
TI  - Kaempferia parviflora, a plant used in traditional medicine to enhance sexual
      performance contains large amounts of low affinity PDE5 inhibitors.
AB  - AIM OF THE STUDY: A number of medicinal plants are used in traditional medicine
      to treat erectile dysfunction. Since cyclic nucleotide PDEs inhibitors underlie
      several current treatments for this condition, we sought to show whether these
      plants might contain substantial amounts of PDE5 inhibitors. MATERIALS AND
      METHODS: Forty one plant extracts and eight 7-methoxyflavones from Kaempferia
      parviflora Wall. ex Baker were screened for PDE5 and PDE6 inhibitory activities
      using the two-step radioactive assay. The PDE5 and PDE6 were prepared from mice
      lung and chicken retinas, respectively. All plant extracts were tested at 50
      MUg/ml whereas the pure compounds were tested at 10 MUM. RESULTS: From forty one
      plant extracts tested, four showed the PDE5 inhibitory effect. The chemical
      constituents isolated from rhizomes of Kaempferia parviflora were further
      investigated on inhibitory activity against PDE5 and PDE6. The results showed
      that 7-methoxyflavones from this plant showed inhibition toward both enzymes. The
      most potent PDE5 inhibitor was 5,7-dimethoxyflavone (IC(50) = 10.64 +/- 2.09 MUM,
      selectivity on PDE5 over PDE6 = 3.71). Structure activity relationship showed
      that the methoxyl group at C-5 position of 7-methoxyflavones was necessary for
      PDE5 inhibition. CONCLUSIONS: Kaempferia parviflora rhizome extract and its 7
      methoxyflavone constituents had moderate inhibitory activity against PDE5. This
      finding provides an explanation for enhancing sexual performance in the
      traditional use of Kaempferia parviflora. Moreover, 5,7-dimethoxyflavones should
      make a useful lead compound to further develop clinically efficacious PDE5
      inhibitors.

PMID- 21884778
TI  - ent-kaur-16-en-19-oic Acid, isolated from the roots of Aralia continentalis,
      induces activation of Nrf2.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Excessive inflammation can lead to tissue damage
      and dysfunction of vital organs. Hence, regulating inflammatory response is a
      viable therapeutic approach. In Asian countries, various inflammatory diseases
      have often effectively been treated with herbal remedies including the root
      extract of Aralia continentalis Kitagawa (Araliaceae). Here, we investigated the
      effect of kaurenoic acid (ent-kaur-16-en-19-oic acid: KA), a diterpenoid that is
      extracted from Aralia continentalis Kitagawa root, on inflammation. MATERIALS,
      METHODS, AND RESULTS: Western blot and RT-PCR analyses show that KA induced the
      nuclear localization of Nrf2 as low as 1 nM in concentration and that KA
      treatment induced the expression of Nrf2 dependent genes such as GCLC and HO-1.
      On the other hand, KA did not affect the degradation of cytoplasmic IkappaB
      alpha, the nuclear localization of RelA (p65), and NF-kappaB transcriptional
      activity in RAW264.7 cells treated with endotoxin. Consistent with these data, KA
      treatment failed to suppress gene expression of representative pro-inflammatory
      mediators including COX-2, nitric oxide, IL-1beta, TNF-alpha, and IL-12,
      indicating that KA did not have an important impact on NF-kappaB activation.
      CONCLUSION: Together, these results show that KA was an effective activator of
      Nrf2, and suggest that the beneficial effects of Aralia continentalis Kitagawa
      root extract are, at least in part, mediated by activating Nrf2.

PMID- 21884779
TI  - Terminalia macroptera, its current medicinal use and future perspectives.
AB  - The tree Terminalia macroptera (Combretaceae) is widespread in Western Africa,
      and in this area, different parts have been utilized in the treatment of various
      diseases. In this article, we report on the medicinal use of T. macroptera in
      three different districts in Mali (Siby, Dioila and Dogonland), based on
      interviews with 78 healers in these districts. Roots, root bark, stem bark,
      leaves and fruits have all been employed by healers, as has parasitic Loranthus
      species growing on the tree. Major areas of use comprise treatment of wounds and
      sores, infections, pain, cough, tuberculosis and hepatitis. Some of the medicinal
      uses of T. macroptera appear to be rationally explained by its chemical
      constituents.

PMID- 21884780
TI  - Mitochondria, reactive oxygen species, and chronological aging: a message from
      yeast.
AB  - As a major intracellular source of reactive oxygen species (ROS), mitochondria
      are involved in aging and lifespan regulation. Using the yeast chronological
      aging model, researchers have identified conserved signaling pathways that affect
      lifespan by modulating mitochondrial functions. Caloric restriction and a genetic
      mimetic with reduced target of rapamycin signaling globally upregulate the
      mitochondrial proteome and respiratory functions. Recent discoveries support the
      notion that an altered mitochondrial proteome induces mitohormesis. Mitohormesis
      involves a variety of ROS during several growth stages and extends lifespan in
      yeast and other organisms. Here we recap recent advances in understanding of ROS
      as signals that decelerate chronological aging in yeast. We also discuss
      parallels between yeast and worm hypoxic signaling. In sum, this mini-review
      covers mitochondrial regulation by nutrient-sensing pathways and the complex
      underlying interactions of ROS, metabolic pathways, and chronological aging.

PMID- 21884781
TI  - Changes in healthy elderly women's physical performance: a 3-year follow-up.
AB  - BACKGROUND: Inflammatory states, hypovitaminosis D and secondary
      hyperparathyroidism may have a role in the age-related loss of muscle mass, and
      physical performance in healthy old people. The aim of this study is to
      investigate changes in muscle mass, strength and physical performance in healthy,
      active elderly females over a 3-year follow-up, correlating them with any
      inflammatory states and PTH and 25-hydroxyvitamin D (25-OHD) levels. METHODS: One
      hundred healthy females over 65 years of age routinely attending a twice-weekly
      mild fitness program were eligible for the study. Clinical history, serum
      parameters, body composition by DEXA, handgrip strength, knee extensor
      isometric/isotonic strength and functional performance measured using the Short
      Physical Performance Battery (SPPB) were evaluated at the baseline and after 3
      years. RESULTS: After 3 years, the women had a significant decrease in weight (?:
      0.8+/-3.1 kg; p<0.05) and height (?:-0.4+/-0,6 cm; p<0.001), while their BMI and
      body composition parameters did not change. Only IL-6 (?: 0.6+/-2.0; p<0.01) and
      PTH (?: 30.7+/-29.2 ng/L; p<0.001) increased significantly, while there were no
      changes in 25-OHD levels. There was a significant decrease in all the SPPB
      results and in muscle strength. ? PTH only correlated with the variation in 4
      meter walking speed (r: 0.41; p<0.01). CONCLUSIONS: With advancing age, physical
      performance declines even in healthy, active females despite a spare of muscle
      mass. The increase in PTH seems to have a role in this decline, that could be
      clarified by further investigations.

PMID- 21884782
TI  - From wastewater to bioenergy and biochemicals via two-stage bioconversion
      processes: a future paradigm.
AB  - Recovery of bioenergy and biochemicals from wastewater has attracted growing and
      widespread interests. In this respect, two-stage bioconversion process (TSBP)
      offers an appealing avenue to achieve stepwise and directional substrate
      conversion in separated stages. Such a biosystem not only enables enhanced
      degradation of organics, but also favors a high product yield and quality.
      Various TSBRs have been developed for the production of methane, hydrogen,
      electricity, bioplastics, bioflocculants, biopesticides, biosurfactants and other
      value-added products, demonstrating marked advantages over the conventional one
      stage processes. It represents a promising, and likely the sole viable, paradigm
      for future application. However, there are also many remaining challenges. This
      paper provides an overview of the various TSBPs, introduces the recent advances,
      and discusses the major challenges and the future perspectives for practical
      application.

PMID- 21884783
TI  - High plasma thiocyanate levels in smokers are a key determinant of thiol
      oxidation induced by myeloperoxidase.
AB  - Smokers have an elevated risk of atherosclerosis but the origins of this elevated
      risk are incompletely defined, though evidence supports an accumulation of the
      oxidant-generating enzyme myeloperoxidase (MPO) in the inflamed artery wall. We
      hypothesized that smokers would have a high level of thiocyanate (SCN(-)), a
      preferred substrate for MPO, which in turn would predispose to thiol oxidation,
      an established independent risk factor for atherosclerosis. In this study it is
      shown that on exposure to MPO/H(2)O(2), thiols on plasma proteins from nonsmokers
      were increasingly oxidized with increasing added SCN(-) concentrations. Plasma
      from smokers contained significantly higher endogenous levels of SCN(-) than that
      from nonsmokers (131+/-31 vs 40+/-24 MUM, P<0.0001). When plasma from smokers and
      nonsmokers was exposed to MPO/H(2)O(2)-stimulated oxidation, a strong positive
      correlation (r=0.8139, P<0.0001) between the extent of thiol oxidation and the
      plasma SCN(-) concentrations was observed. Computational calculations indicate a
      changeover from HOCl to HOSCN as the major MPO-generated oxidant in plasma, with
      increasing SCN(-) levels. These data indicate that plasma SCN(-) levels are a key
      determinant of the extent of thiol oxidation on plasma proteins induced by MPO,
      and implicate HOSCN as an important mediator of inflammation-induced oxidative
      damage to proteins in smokers.

PMID- 21884784
TI  - Poly(ADP-ribose) polymerase-1 is a key mediator of cisplatin-induced kidney
      inflammation and injury.
AB  - Cisplatin is a commonly used chemotherapeutic drug, the clinical use of which is
      limited by the development of dose-dependent nephrotoxicity. Enhanced
      inflammatory response, oxidative stress, and cell death have been implicated in
      the development of cisplatin-induced nephropathy; however, the precise mechanisms
      are elusive. Overactivation of the nuclear enzyme poly(ADP-ribose) polymerase-1
      (PARP-1) by oxidative DNA damage under various pathological conditions promotes
      cell death and up-regulation of key proinflammatory pathways. In this study,
      using a well-established model of nephropathy, we have explored the role of PARP
      1 in cisplatin-induced kidney injury. Genetic deletion or pharmacological
      inhibition of PARP-1 markedly attenuated the cisplatin-induced histopathological
      damage, impaired renal function (elevated serum BUN and creatinine levels), and
      enhanced inflammatory response (leukocyte infiltration; TNF-alpha, IL-1beta,
      F4/80, adhesion molecules ICAM-1/VCAM-1 expression) and consequent
      oxidative/nitrative stress (4-HNE, 8-OHdG, and nitrotyrosine content; NOX2/NOX4
      expression). PARP inhibition also facilitated the cisplatin-induced death of
      cancer cells. Thus, PARP activation plays an important role in cisplatin-induced
      kidney injury, and its pharmacological inhibition may represent a promising
      approach to preventing the cisplatin-induced nephropathy. This is particularly
      exciting because several PARP inhibitors alone or in combination with DNA
      damaging anticancer agents show considerable promise in clinical trials for
      treatment of various malignancies (e.g., triple-negative breast cancer).

PMID- 21884785
TI  - School achievement in 14-year-old youths prenatally exposed to marijuana.
AB  - The relation between prenatal marijuana exposure (PME) and school achievement was
      evaluated in a sample of 524 14-year-olds. Women were recruited during pregnancy
      and assessed, along with their offspring, at multiple phases from infancy to
      early adulthood. The sample represents a low-income population. Half of the
      adolescents are male and 55% are African American. School achievement was
      assessed with the Wechsler Individual Achievement Test (WIAT) Screener
      (Psychological Corporation, 1992). A significant negative relation was found
      between PME and 14-year WIAT composite and reading scores. The deficit in school
      achievement was mediated by the effects of PME on intelligence test performance
      at age 6, attention problems and depression symptoms at age 10, and early
      initiation of marijuana use. These findings suggest that the effects of PME on
      adolescent achievement are mediated by the earlier negative effects of PME on
      child characteristics. The negative impact of these characteristics on adolescent
      achievement may presage later problems in early adulthood.

PMID- 21884787
TI  - Study of drug concentration effects on in vitro lipolysis kinetics in medium
      chain triglycerides by considering oil viscosity and surface tension.
AB  - Simple oil formulations are widely used in oral drug delivery and the fate of
      these systems is governed mainly by the dispersion and digestion process. The
      current work aimed to study concentration effects of six poorly water-soluble
      drugs on the in vitro lipolysis rate of medium-chain triglycerides. The results
      were compared with drug effects on oil viscosity and surface tension. First the
      different drugs were characterized by molecular modeling and their influence on
      physical oil properties was assessed. Herein capillary viscosimetry was employed
      as well as dynamic surface tensiometry. Subsequently, an apparent in vitro
      lipolysis rate was determined in biorelevant medium using an automated pH stat
      titrator linked to a thermo-controlled vessel. The different drugs exhibited
      varying effects on oil viscosity and surface tension. However, all drugs
      significantly lowered the apparent lipolysis rate of the oil. This effect was
      very similar among the different compounds with exception of orlistat, which
      practically blocked lipolysis because of a potent direct inhibition. The other
      drugs affected lipolysis kinetics most likely by different mechanism(s). In light
      of the obtained results, a drug effect on oil viscosity or surface tension
      appeared to play a minor role in reducing the lipolysis rate. The lipolysis
      kinetics was further not affected by the drug load, which was deemed advantageous
      from a pharmaceutical viewpoint. Different dose strengths are therefore not
      assumed to alter lipolysis kinetics, which is beneficial for limiting the
      variability of in vivo drug release. Further studies of drug solubility kinetics
      in the evolving digestion phases are, however, needed to finally assess potential
      effects of dosage strength in simple oil formulations.

PMID- 21884786
TI  - Developmental functions for the Caenorhabditis elegans Sp protein SPTF-3.
AB  - Sp factors are important for animal development and the transcriptional
      regulation of a wide variety of genes. How they influence the developmental
      decisions of individual cells within the organism, however, is poorly understood.
      To better understand the developmental functions for Sp transcription factors, we
      have characterized the functions of Caenorhabditis elegans SPTF-3 using RNAi
      knockdown and a non-null, hypomorphic mutant allele. We find that disruption of
      sptf-3 confers a variety of developmental defects, including defects in
      development of the egg-laying system, oocyte production, and embryonic
      morphogenesis. sptf-3 mutants exhibit defects in vulval lineage polarity, a
      phenotype previously only observed in mutants defective in Wnt signaling. We show
      that the embryonic function of sptf-3 is dependent on germline activity, arguing
      that the gene has an important maternal contribution to embryonic development. An
      evaluation of reporter gene expression suggests that SPTF-3 exhibits specificity,
      in that it can influence the expression of a given gene in some cells but not
      others, and that SPTF-3 participates in the maintenance of gene expression states
      in differentiated cells. We propose SPTF-3 provides a good model to study the in
      vivo functions for Sp transcription factors during animal development.

PMID- 21884788
TI  - Preparation and characterization of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)
      (PHBHHX) based nanoparticles for targeted cancer therapy.
AB  - Targeted drug delivery systems are one of the most promising alternatives for the
      cancer therapy. Rapid developments on nanomedicine facilitated the creation of
      novel nanotherapeutics by using different nanomaterials. Especially polymer based
      nanoparticles are convenient for this purpose. In this study; a natural polymer
      (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate), PHBHHX) was used as a base matrix
      for the production of a novel nanotherapeutic including antineoplastic agent,
      Etoposide and attached folic acid as a ligand on the nanoparticles. Modified
      solvent evaporation technique was used for the production of PHBHHX nanoparticles
      and the average size of the obtained PHBHHX nanoparticles were observed in the
      range of 180 nm and 1.5 MUm by the change in experimental conditions (i.e.,
      homogenization rate, surfactant concentration and polymer/solvent ratio). By the
      increase in homogenization rate and surfactant concentration, size of the
      nanoparticles was decreased, while the size was increased by the increase in
      polymer/solvent ratio. Drug loading ratio was also found to be highly affected by
      polymer/drug ratio. Surface charge of the prepared nanoparticles was also
      investigated by zeta potential measurements. In the cytotoxicity tests; Etoposide
      loaded and folic acid attached PHBHHX nanoparticles were observed as more
      effective on HeLa cells than Etoposide loaded PHBHHX nanoparticles without
      attached folic acid. The cytotoxicity of folic acid conjugated PHBHHX
      nanoparticles to cancer cells was found to be much higher than that of normal
      fibroblast cells, demonstrating that the folate conjugated nanoparticles has the
      ability to selectively target to cancer cells. In addition, apoptotic/necrotic
      activities were evaluated for all formulations of the PHBHHX nanoparticles and
      parallel results with cytotoxicity tests were obtained. These studies demonstrate
      that the folic acid attached and Etoposide loaded PHBHHX nanoparticles seem as
      promising for the targeted cancer therapy.

PMID- 21884789
TI  - Investigations on the effect of different cooling rates on the stability of
      amorphous indomethacin.
AB  - Amorphous forms of indomethacin have previously been prepared using various
      preparation techniques and it could be demonstrated that the way the material was
      prepared influenced the physicochemical properties of the amorphous form of the
      drug. The aim of this study was to use one preparation technique (transformation
      via the melt) to prepare amorphous indomethacin and to investigate the influence
      of the cooling rate (as a processing parameter) on the physical stability of the
      resulting amorphous form. The amorphous materials obtained were analysed for
      their structural characteristics using Raman spectroscopy in combination with
      multivariate data analysis. The onset of crystallisation was determined as an
      indicator of the physical stability of the materials using differential scanning
      calorimetry (DSC) and polarising light microscopy. The Johnson-Mehl-Avrami (JMA)
      model and Sestak-Berggren (SB) model were used in this study to describe the non
      isothermal crystallisation behaviour. All differently cooled samples were
      completely X-ray amorphous. Principal component analysis of the Raman spectra of
      the various amorphous forms revealed that the samples clustered in the scores
      plot according to the cooling rate, suggesting structural differences between the
      differently cooled samples. The minimum cooling rate required to obtain amorphous
      indomethacin was 1.2 K min(-1), as assessed from the time-temperature
      transformation (TTT) diagram. The physical stability of the samples was found to
      increase as a function of cooling rate in the order of 30 K min(-1) > 20 K min(
      1) > 10 K min(-1) > 5 K min(-1) > 3 K min(-1) ~ 1.2 K min(-1) and was in
      agreement with calculated descriptors for the glass forming ability (GFA),
      including the reduced glass transition temperature (T(rg)) and the reduced
      temperature (T(red)). The JMA model could not be applied to describe the
      crystallisation process for the differently cooled melts of indomethacin in this
      study. The kinetic exponent M from the autocatalytic SB model however, showed a
      positive correlation with glass stability.

PMID- 21884790
TI  - Hydroxysteroid dehydrogenases (HSDs) in bacteria: a bioinformatic perspective.
AB  - Steroidal compounds including cholesterol, bile acids and steroid hormones play a
      central role in various physiological processes such as cell signaling, growth,
      reproduction, and energy homeostasis. Hydroxysteroid dehydrogenases (HSDs), which
      belong to the superfamily of short-chain dehydrogenases/reductases (SDR) or aldo
      keto reductases (AKR), are important enzymes involved in the steroid hormone
      metabolism. HSDs function as an enzymatic switch that controls the access of
      receptor-active steroids to nuclear hormone receptors and thereby mediate a fine
      tuning of the steroid response. The aim of this study was the identification of
      classified functional HSDs and the bioinformatic annotation of these proteins in
      all complete sequenced bacterial genomes followed by a phylogenetic analysis. For
      the bioinformatic annotation we constructed specific hidden Markov models in an
      iterative approach to provide a reliable identification for the specific
      catalytic groups of HSDs. Here, we show a detailed phylogenetic analysis of
      3alpha-, 7alpha-, 12alpha-HSDs and two further functional related enzymes (3
      ketosteroid-Delta(1)-dehydrogenase, 3-ketosteroid-Delta(4)(5alpha)-dehydrogenase)
      from the superfamily of SDRs. For some bacteria that have been previously
      reported to posses a specific HSD activity, we could annotate the corresponding
      HSD protein. The dominating phyla that were identified to express HSDs were that
      of Actinobacteria, Proteobacteria, and Firmicutes. Moreover, some evolutionarily
      more ancient microorganisms (e.g., Cyanobacteria and Euryachaeota) were found as
      well. A large number of HSD-expressing bacteria constitute the normal human
      gastro-intestinal flora. Another group of bacteria were originally isolated from
      natural habitats like seawater, soil, marine and permafrost sediments. These
      bacteria include polycyclic aromatic hydrocarbons-degrading species such as
      Pseudomonas, Burkholderia and Rhodococcus. In conclusion, HSDs are found in a
      wide variety of microorganisms including bacteria and archaea, suggesting that
      steroid metabolism is an evolutionarily conserved mechanism that might serve
      different functions such as nutrient supply and signaling. Article from a special
      issue on steroids and microorganisms.

PMID- 21884791
TI  - Long term perturbation of endocrine parameters and cholesterol metabolism after
      discontinued abuse of anabolic androgenic steroids.
AB  - AIMS: To study the long-term impact of anabolic androgenic steroid (AAS) abuse on
      the cholesterol profile, and the potential to suppress endocrine activity in men
      working out at gym facilities. To study the relation between urinary biomarkers
      for testosterone and nandrolone abuse and the UGT2B17 genotype and time profile.
      EXPERIMENTAL DESIGN: Subjects (N = 56) were recruited through Anti-Doping Hot
      Line. Serum levels of luteinizing hormone (LH), follicle-stimulating hormone
      (FSH), plasma levels of low density lipoprotein (LDL), high density lipoprotein
      (HDL) and urinary steroid profile were regularly measured for a period of up to
      one year after cessation of intramuscular AAS abuse. RESULTS AND DISCUSSION: A
      sustained suppression of LH, and FSH was observed for several months. The
      nandrolone urinary biomarker 19-NA was detectable several months after the last
      nandrolone intake and was correlated to the levels of LH and FSH. Testosterone
      abuse on the other hand was detectable only for a few weeks, and some of the
      testosterone abusers did not test positive due to a genetic deletion polymorphism
      of the UGT2B17. Significantly increased levels of HDL and decreased levels of LDL
      were observed for 6-months after cessation of AAS abuse. CONCLUSION: Some
      individuals had a sustained suppression of LH and FSH for a period of 1 year
      whereas the cholesterol profile was normalized within 6 month. The long term
      consequences of these findings remain to be established.

PMID- 21884792
TI  - The role of residue C410 on activation of the human vitamin D receptor by various
      ligands.
AB  - Nuclear receptors (NRs) are ligand-activated transcription factors that regulate
      the expression of genes involved in biologically important processes. The human
      vitamin D receptor (hVDR) is a member of the NR superfamily and is responsible
      for maintaining calcium and phosphate homeostasis. This receptor is activated by
      its natural ligand, 1alpha, 25-dihydroxyvitamin D(3) (1alpha, 25(OH)(2)D(3)), as
      well as bile acids such as lithocholic acid (LCA). Disruption of molecular
      interactions between the hVDR and its natural ligand result in adverse diseases,
      such as rickets, making this receptor a good target for drug discovery. Previous
      mutational analyses of the hVDR have mainly focused on residues lining the
      receptor's ligand binding pocket (LBP) and techniques such as alanine scanning
      mutagenesis and site-directed mutagenesis. In this work, a rationally designed
      hVDR library using randomized codons at selected positions provides insight into
      the role of residue C410, particularly on activation of the receptor by various
      ligands. A variant, C410Y, was engineered to bind LCA with increased sensitivity
      (EC(50) value of 3 MUM and a 34-fold activation) in mammalian cell culture
      assays. Furthermore, this variant displayed activation with a novel small
      molecule, cholecalciferol (chole) which does not activate the wild-type receptor,
      with an EC(50) value of 4 MUM and a 25-fold activation. The presence of a bulky
      residue at this position, such as a tyrosine or phenylalanine, may contribute
      towards molecular interactions that allow for the enhanced activation with LCA
      and novel activation with chole. Additional bulk at the same end of the pocket,
      such as in the case of the variant H305F; C410Y enhances the receptor's
      sensitivity for these ligands further, perhaps due to the filling of a cavity.
      The effects of residue C410 on specificity and activation with the different
      ligands studied were unforeseen, as this residue does not line the hVDR's LBP.
      Further investigating of the structure-function relationships between the hVDR
      and its ligands, including the mutational tolerance of residues within as well as
      outside the LBP, is needed for a comprehensive understanding of the functionality
      and interactions of the receptor with these ligands and for development of new
      small molecules as potential therapeutic drugs.

PMID- 21884793
TI  - Combined gene overexpression of neuropeptide Y and its receptor Y5 in the
      hippocampus suppresses seizures.
AB  - We recently demonstrated that recombinant adeno-associated viral vector-induced
      hippocampal overexpression of neuropeptide Y receptor, Y2, exerts a seizure
      suppressant effect in kindling and kainate-induced models of epilepsy in rats.
      Interestingly, additional overexpression of neuropeptide Y in the hippocampus
      strengthened the seizure-suppressant effect of transgene Y2 receptors. Here we
      show for the first time that another neuropeptide Y receptor, Y5, can also be
      overexpressed in the hippocampus. However, unlike Y2 receptor overexpression,
      transgene Y5 receptors in the hippocampus had no effect on kainate-induced motor
      seizures in rats. However, combined overexpression of Y5 receptors and
      neuropeptide Y exerted prominent suppression of seizures. This seizure
      suppressant effect of combination gene therapy with Y5 receptors and neuropeptide
      Y was significantly stronger as compared to neuropeptide Y overexpression alone.
      These results suggest that overexpression of Y5 receptors in combination with
      neuropeptide Y could be an alternative approach for more effective suppression of
      hippocampal seizures.

PMID- 21884794
TI  - IGF-1 delivery to CNS attenuates motor neuron cell death but does not improve
      motor function in type III SMA mice.
AB  - The efficacy of administering a recombinant adeno-associated virus (AAV) vector
      encoding human IGF-1 (AAV2/1-hIGF-1) into the deep cerebellar nucleus (DCN) of a
      type III SMA mouse model was evaluated. High levels of IGF-1 transcripts and
      protein were detected in the spinal cord at 2 months post-injection demonstrating
      that axonal connections between the cerebellum and spinal cord were able to act
      as conduits for the viral vector and protein to the spinal cord. Mice treated
      with AAV2/1-hIGF-1 and analyzed 8 months later showed changes in endogenous Bax
      and Bcl-xl levels in spinal cord motor neurons that were consistent with IGF-1
      mediated anti-apoptotic effects on motor neurons. However, although AAV2/1-hIGF-1
      treatment reduced the extent of motor neuron cell death, the majority of rescued
      motor neurons were non-functional, as they lacked axons that innervated the
      muscles. Furthermore, treated SMA mice exhibited abnormal muscle fibers, aberrant
      neuromuscular junction structure, and impaired performance on motor function
      tests. These data indicate that although CNS-directed expression of IGF-1 could
      reduce motor neuron cell death, this did not translate to improvements in motor
      function in an adult mouse model of type III SMA.

PMID- 21884795
TI  - Long-term methylglyoxal treatment impairs smooth muscle contractility in organ
      cultured rat mesenteric artery.
AB  - Methylglyoxal (MGO), a metabolite of glucose accumulates in vascular tissues of
      hypertensive rats. We recently showed that short-term (30min) treatment with MGO
      inhibits noradrenaline (NA)-induced smooth muscle contraction in rat aorta and
      mesenteric artery. In the present study, long-term effect of MGO was examined
      using organ culture method. The contractility, morphology, and protein expression
      of rat mesenteric artery after organ culture with MGO for 3 days were examined.
      MGO (4 and 42MUM) inhibited NA (0.1nM to 3MUM) or KCl (72.7mM)-induced
      contraction. The inhibitory effect was higher in endothelium-denuded than
      endothelium-intact artery. An anti-oxidant drug, N-acetyl-l-cysteine (NAC; 1mM)
      or an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
      (NOX), gp91ds-tat (0.1MUM) prevented the inhibitory effect of MGO. MGO increased
      superoxide production as detected by lucigenin assay. In the medial layer of the
      arteries cultured with MGO, apoptotic morphological change was observed, and NAC
      or gp91ds-tat prevented it. MGO significantly increased expression of a homolog
      of gp91(phox), NOX1 but not gp91(phox) as determined by Western blotting. An NF
      kappaB inhibitor, pyrrolidine dithiocarbamate prevented the MGO-induced NOX1
      expression. MGO had no effect on protein expression of p22(phox), p67(phox),
      p47(phox), as well as superoxide dismutase (SOD)-1, SOD-2 and SOD-3. Present
      results indicate that long-term MGO treatment has an inhibitory effect on
      contractility of isolated blood vessel, which is likely mediated via increased
      NOX1-derived superoxide production and subsequent apoptosis.

PMID- 21884796
TI  - Minocycline exerts uncoupling and inhibiting effects on mitochondrial respiration
      through adenine nucleotide translocase inhibition.
AB  - The present study was aimed to provide a better understanding of the mitochondria
      targeted actions of minocycline (MC), a second-generation tetracycline which has
      cytoprotective effects. Although the specific mechanisms underlying its activity
      remained elusive, considerable amounts of data indicated mitochondria as the
      primary pharmacological target of MC. Previous reports have shown that MC affects
      the oxygen-uptake rate by isolated mitochondria in different respiratory states.
      Here, we report on the effect of MC, in the range 50-200MUM, on mitochondrial
      respiration. State 3 respiration titration with carboxyatractyloside revealed
      that MC inhibits the adenine nucleotide translocase. Furthermore, we analyze MC
      channel-forming capacity in the lipid membrane bilayer. Our results confirmed the
      crucial role of Deltapsi and showed a dependence on Ca(2+) for MC to have an
      effect on mitochondria. Our data also indicated that outer and inner
      mitochondrial membranes contribute differently to this effect, involving the
      presence of Deltapsi (the inner membrane) and VDAC (the outer membrane). Data
      from three isosmotic media indicate that MC does not increase the permeability of
      the inner membrane to protons or potassium. In addition, by using mitoplasts and
      ruthenium red, we showed that Ca(2+) uptake is not involved in the MC effect,
      suggesting involvement of VDAC in the MC interaction with the outer membrane. Our
      data contribute to unravel the mechanisms behind the mitochondria-targeted
      activity of the cytoprotective drug MC.

PMID- 21884798
TI  - Simultaneous visualization of multiple neuronal properties with single-cell
      resolution in the living rodent brain.
AB  - To understand the fine-scale structures and functional properties of individual
      neurons in vivo, we developed and validated a rapid genetic technique that
      enables simultaneous investigation of multiple neuronal properties with single
      cell resolution in the living rodent brain. Our technique PASME (promoter
      assisted sparse-neuron multiple-gene labeling using in uteroelectroporation)
      targets specific small subsets of sparse pyramidal neurons in layer 2/3, layer 5
      of the cerebral cortex and in the hippocampus with multiple fluorescent reporter
      proteins such as postsynaptic PSD-95-GFP and GFP-gephyrin. The technique is also
      applicable for targeting independently individual neurons and their presynaptic
      inputs derived from surrounding neurons. Targeting sparse layer 2/3 neurons, we
      uncovered a novel subpopulation of layer 2/3 neurons in the mouse cerebral
      cortex. This technique, broadly applicable for probing and manipulating neurons
      with single-cell resolution in vivo, should provide a robust means to uncover the
      basic mechanisms employed by the brain, especially when combined with in vivo two
      photon laser-scanning microscopy and/or optogenetic technologies.

PMID- 21884797
TI  - Ubiquitin-dependent endocytosis, trafficking and turnover of neuronal membrane
      proteins.
AB  - Extracellular signaling between cells is often transduced via receptors that
      reside at the cell membrane. In neurons this receptor-mediated signaling can
      promote a variety of cellular events such as differentiation, axon outgrowth and
      guidance, and synaptic development and function. Endocytic membrane trafficking
      of receptors ensures that the strength and duration of an extracellular signal is
      properly regulated. The covalent modification of membrane proteins by ubiquitin
      is a key biological mechanism controlling receptor internalization and endocytic
      sorting to recycling and degradative pathways in many cell types. In this review
      we highlight recent findings regarding the ubiquitin-dependent trafficking and
      turnover of receptors in neurons and the implications for neuronal development
      and function.

PMID- 21884799
TI  - Tandem repeats in proteins: from sequence to structure.
AB  - The bioinformatics analysis of proteins containing tandem repeats requires
      special computer programs and databases, since the conventional approaches
      predominantly developed for globular domains have limited success. Here, I survey
      bioinformatics tools which have been developed recently for identification and
      proteome-wide analysis of protein repeats. The last few years have also been
      marked by an emergence of new 3D structures of these proteins. Appraisal of the
      known structures and their classification uncovers a straightforward relationship
      between their architecture and the length of the repetitive units. This
      relationship and the repetitive character of structural folds suggest rules for
      better prediction of the 3D structures of such proteins. Furthermore,
      bioinformatics approaches combined with low resolution structural data, from
      biophysical techniques, especially, the recently emerged cryo-electron
      microscopy, lead to reliable prediction of the protein repeat structures and
      their mode of binding with partners within molecular complexes. This hybrid
      approach can actively be used for structural and functional annotations of
      proteomes.

PMID- 21884800
TI  - Multi-scale mineralogical characterization of the hypercalcified sponge
      Petrobiona massiliana (Calcarea, Calcaronea).
AB  - The massive basal skeleton of a few remnant living hypercalcified sponges
      rediscovered since the 1960s are valuable representatives of ancient calcium
      carbonate biomineralization mechanisms in basal Metazoa. A multi-scale
      mineralogical characterization of the easily accessible Mediterranean living
      hypercalcified sponge belonging to Calcarea, Petrobiona massiliana (Vacelet and
      Levi, 1958), was conducted. Oriented observations in light and electron
      microscopy of mature and growing areas of the Mg-calcite basal skeleton were
      combined in order to describe all structural levels from the submicronic to the
      macroscopic scale. The smallest units produced are ca. 50-100nm grains that are
      in a mushy amorphous state before their crystallization. Selected area electron
      diffraction (SAED) further demonstrated that submicronic grains are assembled
      into crystallographically coherent clusters or fibers, the latter are even
      laterally associated into single-crystal bundles. A model of crystallization
      propagation through amorphous submicronic granular units is proposed to explain
      the formation of coherent micron-scale structural units. Finally, XRD and EELS
      analyses highlighted, respectively, inter-individual variation of skeletal Mg
      contents and heterogeneous spatial distribution of Ca ions in skeletal fibers.
      All mineralogical features presented here cannot be explained by classical
      inorganic crystallization principles in super-saturated solutions, but rather
      underlined a highly biologically regulated formation of the basal skeleton. This
      study extending recent observations on corals, mollusk and echinoderms confirms
      that occurrence of submicronic granular units and a possible transient amorphous
      precursor phase in calcium carbonate skeletons is a common biomineralization
      strategy already selected by basal metazoans.

PMID- 21884801
TI  - A novel framework for longitudinal atlas construction with groupwise registration
      of subject image sequences.
AB  - Longitudinal atlas construction plays an important role in medical image
      analysis. Given a set of longitudinal images from different subjects, the task of
      longitudinal atlas construction is to build an atlas sequence which can represent
      the trend of anatomical changes of the population. The major challenge for
      longitudinal atlas construction is how to effectively incorporate both the
      subject-specific information and population information to build the unbiased
      atlases. In this paper, a novel groupwise longitudinal atlas construction
      framework is proposed to address this challenge, and the main contributions of
      the proposed framework lie in the following aspects: (1) The subject-specific
      longitudinal information is captured by building the growth model for each
      subject. (2) The longitudinal atlas sequence is constructed by performing
      groupwise registration among all the subject image sequences, and only one
      transformation is needed to transform each subject's image sequence to the atlas
      space. The constructed longitudinal atlases are unbiased and no explicit template
      is assumed. (3) The proposed method is general, where the number of longitudinal
      images of each subject and the time points at which they are taken can be
      different. The proposed method is extensively evaluated on two longitudinal
      databases, namely the BLSA and ADNI databases, to construct the longitudinal
      atlas sequence. It is also compared with a state-of-the-art longitudinal atlas
      construction algorithm based on kernel regression on the temporal domain.
      Experimental results demonstrate that the proposed method consistently achieves
      higher registration accuracies and more consistent spatial-temporal
      correspondences than the compared method on both databases.

PMID- 21884802
TI  - Not quite PIB-positive, not quite PIB-negative: slight PIB elevations in elderly
      normal control subjects are biologically relevant.
AB  - Researchers employing Pittsburgh Compound B positron emission tomography (PIB
      PET) imaging have consistently indentified old normal control (oNC) subjects with
      elevated tracer uptake, suggesting the presence of beta-amyloid deposition in
      these individuals. However, a consensus regarding the level at which PIB reveals
      a biologically meaningful signal does not exist (ie. an appropriate cutoff value
      for PIB positivity remains unclear). In this exploratory study, we sought to
      investigate the range of PIB distribution volume ratio (DVR) values present in
      our oNC cohort (N=75, age range=58-97). oNC subjects were classified based on
      global PIB index values (average DVR across prefrontal, parietal, lateral
      temporal and cingulate cortices) by employing two approaches: (1) an iterative
      outlier approach that revealed a cutoff value of 1.16 (IO-cutoff) and (2) an
      approach using data from a sample of young normal control subjects (N=11, age
      range=20-30) that yielded a cutoff value of 1.08 (yNC-cutoff). oNC subjects
      falling above the IO-cutoff had values similar to AD subjects ("PIB+", 15%).
      Subjects falling between the 2 cutoffs were considered to have ambiguous PIB
      status ("Ambig", 20%) and the remaining oNC were considered "PIB-" (65%).
      Additional measures capturing focal DVR magnitude and extent of elevated DVR
      values were consistent with the classification scheme using PIB index values, and
      revealed evidence for elevated DVR values in a subset of PIB- oNC subjects.
      Furthermore, there were a greater proportion of ambiguously elevated values
      compared to low values, and these elevated values were present in regions known
      to show amyloid deposition. The analyses presented in this study, in conjunction
      with recently published pathological data, suggest a biological relevance of
      slight PIB elevations in aging.

PMID- 21884803
TI  - Search for patterns of functional specificity in the brain: a nonparametric
      hierarchical Bayesian model for group fMRI data.
AB  - Functional MRI studies have uncovered a number of brain areas that demonstrate
      highly specific functional patterns. In the case of visual object recognition,
      small, focal regions have been characterized with selectivity for visual
      categories such as human faces. In this paper, we develop an algorithm that
      automatically learns patterns of functional specificity from fMRI data in a group
      of subjects. The method does not require spatial alignment of functional images
      from different subjects. The algorithm is based on a generative model that
      comprises two main layers. At the lower level, we express the functional brain
      response to each stimulus as a binary activation variable. At the next level, we
      define a prior over sets of activation variables in all subjects. We use a
      Hierarchical Dirichlet Process as the prior in order to learn the patterns of
      functional specificity shared across the group, which we call functional systems,
      and estimate the number of these systems. Inference based on our model enables
      automatic discovery and characterization of dominant and consistent functional
      systems. We apply the method to data from a visual fMRI study comprised of 69
      distinct stimulus images. The discovered system activation profiles correspond to
      selectivity for a number of image categories such as faces, bodies, and scenes.
      Among systems found by our method, we identify new areas that are deactivated by
      face stimuli. In empirical comparisons with previously proposed exploratory
      methods, our results appear superior in capturing the structure in the space of
      visual categories of stimuli.

PMID- 21884804
TI  - Control processes during selective long-term memory retrieval.
AB  - In our daily life, we often need to selectively remember information related to
      the same retrieval cue in a consecutive manner (e.g., ingredients from a recipe).
      To investigate such selection processes during cued long-term memory (LTM)
      retrieval, we used a paradigm in which the retrieval demands were systematically
      varied from trial to trial and analyzed, by means of behavior and slow cortical
      EEG potentials (SCPs), the retrieval processes in the current trial depending on
      those of the previous trial. We varied whether the retrieval cue, the type of to
      be-retrieved association (feature), or retrieval load was repeated or changed
      from trial to trial. The behavioral data revealed a benefit of feature
      repetition, probably due to trial-by-trial feature priming. SCPs further showed
      an effect of cue change with a mid-frontal maximum, suggesting increased control
      demands when the cue was repeated, as well as a parietal effect of retrieval-load
      change, indicating increased activation of posterior neural resources when
      focusing on a single association after all learned associations had been
      activated previously, compared to staying with single associations across trials.
      These effects suggest the existence of two distinct types of dynamic (trial-by
      trial) control processes during LTM retrieval: (1) medial frontal processes that
      monitor or regulate interference within a set of activated associations, and (2)
      posterior processes regulating attention to LTM representations. The present
      study demonstrates that processes mediating selective LTM retrieval can be
      successfully studied by manipulating the history of processing demands in trial
      sequences.

PMID- 21884805
TI  - Convergence and divergence of thickness correlations with diffusion connections
      across the human cerebral cortex.
AB  - Cortical thickness correlation across individuals has been observed. So far, it
      remains unclear to what extent such a correlation in thickness is a reflection of
      underlying fiber connection. Here we explicitly compared the patterns of cortical
      thickness correlation and diffusion-based fiber connection across the entire
      cerebral cortex, in 95 normal adults. Interregional thickness correlations were
      extracted by using computational neuroanatomy algorithms based on structural MRI,
      and diffusion connections were detected by using diffusion probabilistic
      tractography. Approximately 35-40% of thickness correlations showed convergent
      diffusion connections across the cerebral cortex. Intriguingly, the observed
      convergences between thickness correlation and diffusion connection are mostly
      focused on the positive thickness correlations, while almost all of the negative
      correlations (>90%) did not have a matched diffusion connection, suggesting
      different mechanisms behind the positive and negative thickness correlations, the
      latter not being mediated by a direct fiber pathway. Furthermore, graph theoretic
      analysis reveals that the thickness correlation network has a more randomized
      overall topology, whereas the nodal characteristics of cortical regions in these
      two networks are statistically correlated. These findings indicate that thickness
      correlations partly reflect underlying fiber connections but they contains
      exclusive information, and therefore should not be simply taken as a proxy
      measure for fiber connections.

PMID- 21884806
TI  - Ancient drainages divide cryptic species in Australia's arid zone: morphological
      and multi-gene evidence for four new species of Beaked Geckos (Rhynchoedura).
AB  - Deserts and other arid zones remain among the least studied biomes on Earth.
      Emerging genetic patterns of arid-distributed biota suggest a strong link between
      diversification history and both the onset of aridification and more recent
      cycles of severe aridification. A previous study based on 1 kb of mtDNA of the
      monotypic gecko genus Rhynchoedura identified five allopatric clades across the
      vast Australian arid zone. We supplemented this data with 2.2kb from three
      nuclear loci and additional mtDNA sequences. Phylogenetic relationships estimated
      from the mtDNA data with ML and Bayesian methods were largely concordant with
      relationships estimated with the nDNA data only, and mtDNA and nDNA data
      combined. These analyses, and coalescent-based species-tree inference methods
      implemented with (*)BEAST, largely resolve the relationships among them. We also
      carried out an examination of 19 morphological characters for 268 museum
      specimens from across Australia, including all 197 animals for which we sequenced
      mtDNA. The mtDNA clades differ subtly in a number of morphological features, and
      we describe three of them as new species, raise a fourth from synonymy, and
      redescribe it and the type species, Rhynchoedura ornata. We also describe a
      morphologically distinctive new species from Queensland based on very few
      specimens. The distribution of arid zone clades across what is now relatively
      homogeneous sand deserts seems to be related to a topographic divide between the
      western uplands and eastern lowlands, with species' distributions correlated with
      dryland rivers and major drainage divides. The existence of five cryptic species
      within the formerly monotypic Rhynchoedura points to ancient divergences within
      the arid zone that likely were driven by wet phases as well as dry ones.

PMID- 21884807
TI  - Feasibility of bone density evaluation using plain digital radiography.
AB  - OBJECTIVE: For the radiographic evaluation of subchondral bone changes
      (sclerosis) in osteoarthritis (OA), bone density (BD) is commonly subjectively
      assessed. BD evaluation using plain digital radiography might be influenced by
      acquisition and post-processing (PP) settings. Objective of this study was to
      evaluate the effects of these settings on the measurement of BD using digital
      radiographs. METHODS: A bone density standard (BDS) of hydroxyapatite (HA)
      mimicked a BD range of 1.0-5.75 g/cm(2). Digital radiographs were acquired with
      variation in acquisition settings, and with clinical and minimal PP. An aluminum
      step wedge served as an internal reference to express the gray values of the BDS
      in mm aluminum equivalents (mmAl). The relation (R(2)) between actual BD and BD
      normalized to the reference wedge was evaluated with linear regression analyses
      for radiographs with variations in PP and acquisition settings. Precision of BD
      measurement of the BDS was evaluated for application in clinical practice.
      RESULTS: The correlation between actual BD and BD normalized to the reference was
      improved by changing PP from clinical (R(2)=0.96) to minimal (R(2)=0.98). Higher
      tube voltage [kilovolt (kV)] improved the correlation further. Even for clinical
      PP, average standard deviation (SD) was 0.97 mmAl, much smaller than the change
      of 2.51 mmAl clinically observed in early OA, which implies the feasibility of BD
      measurements on digital radiographs. CONCLUSION: Changing PP and acquisition
      settings in clinical practice can have profound effect on outcome. If done with
      care, accurate BD measurement is feasible using plain digital radiography.

PMID- 21884808
TI  - Chondroitin sulfate effect on induced arthritis in rats.
AB  - OBJECTIVE: Rodent models of osteoarthritis and rheumatoid arthritis are useful
      tools to study these disease processes. Adjuvant arthritis (AAR) is a model of
      polyarthritis widely used for preclinical testing of antiarthritis substances. We
      report the effect of two different doses of highly purified chondroitin sulfate
      (CS) pharmaceutical grade in the AAR animal model after oral administration.
      DESIGN: AAR was induced by a single intradermal injection of heat-inactivated
      Mycobacterium butyricum in incomplete Freund's adjuvant. The experiments included
      healthy animals, untreated arthritic animals, arthritic animals having been
      administered 300 or 900 mg/kg of CS daily, 14 days before AAR induction until the
      end of the experiment (day 28), arthritic animals having been administered 300 or
      900 mg/kg of CS daily, from day 1 until the end of the experiment. RESULTS: CS
      was capable of significantly reducing the severity of arthritis along with
      oxidative stress, a consequence of chronic inflammatory processes occurring in
      AAR. The CS pre-treatment regimen was effective throughout the whole subacute
      phase, while treatment from day 1 proved effective only in the chronic period.
      The effects were confirmed by improved total antioxidant status and gamma
      glutamyltransferase activity. CS administered under a pre-treatment regimen was
      also able to reduce the production of pro-inflammatory cytokines, C-reactive
      protein in plasma, phagocytic activity and the intracellular oxidative burst of
      neutrophils. CONCLUSIONS: CS proved to be effective in slowing down AAR
      development and in reducing disease markers, thus supporting its beneficial
      activity as a drug in humans.

PMID- 21884809
TI  - Contralateral cane use and knee joint load in people with medial knee
      osteoarthritis: the effect of varying body weight support.
AB  - OBJECTIVE: To evaluate the effect of varying body weight support (BWS) with
      contralateral cane use on medial knee load, measured by external knee adduction
      moment (KAM), in medial knee osteoarthritis (OA) participants. Influences of cane
      use technique, pain and malalignment on the cane's load-reducing effects were
      investigated. METHOD: Participants (n=23) underwent three-dimensional gait
      analysis to measure KAM peaks (early and late stance) and impulse. Unaided
      walking was firstly analyzed. Following cane use training, participants placed
      pre-determined magnitudes of BWS through the cane (10%, 15% and 20% in random
      order), with visual feedback provided via a force-instrumented cane and
      projection screen. Contributions of cane use technique (peak BWS magnitude and
      timing, cane impulse (BWS*time) anterior and lateral cane distance from limb) and
      Western Ontario McMaster Universities OA Index (WOMAC) pain and malalignment to
      KAM outcomes were evaluated using linear mixed models. RESULTS: Cane use reduced
      all KAM variables, with a dose-response effect apparent. Cane BWS impulse was
      important in reducing the early stance peak KAM (P<0.001), peak BWS for late
      stance KAM (P<0.001) and both BWS measures for KAM impulse reductions (P<0.001).
      Variables contributing to efficacy of load-reduction differed across outcomes.
      Generally, greater reductions were achieved with longer lateral cane distances,
      peak BWS timing similar to KAM peaks, and shorter anterior cane distances.
      Greater pain and varus alignment improved load-reduction for some outcomes.
      CONCLUSION: Contralateral cane use significantly reduced medial knee load, with a
      dose-response effect. Medial knee OA patients should be encouraged to maintain
      greater BWS across stance, with cane placement more lateral for optimum benefit.

PMID- 21884810
TI  - Relationship between arthroscopic joint evaluation and the levels of Coll2-1,
      Coll2-1NO(2), and myeloperoxidase in the blood and synovial fluid of horses
      affected with osteochondrosis of the tarsocrural joint.
AB  - OBJECTIVE: To evaluate the levels of plasmatic and synovial Coll2-1, Coll2-1NO(2)
      and myeloperoxidase (MPO) in horses with osteochondral lesions of the tarsocrural
      joint and to investigate how these levels relate to arthroscopic findings of
      inflammation and degeneration. MATERIALS AND METHODS: Venous blood and synovial
      fluid samples were collected from 63 horses presented for arthroscopic removal of
      osteochondral fragments in the tarsocrural joint. Prior to removal of the
      osteochondral fragment, an exploration of the joint was performed and an
      inflammatory and degenerative score was determined. The blood and synovial levels
      of Coll2-1, Coll2-1NO(2) and MPO were also measured. The effects of the
      arthroscopic evaluation (inflammatory and degenerative classes) on the blood and
      synovial markers were evaluated using a linear model (GLM procedure), and
      correlations between biochemical markers in the blood and synovial fluid and the
      arthroscopic evaluation (inflammatory and degenerative classes) were established
      (Pearson's correlations). RESULTS: Significantly higher levels of Coll2-1 were
      detected in synovial fluid of higher degenerative classes. There was a
      significant correlation between the degenerative score and the synovial levels of
      Coll2-1 (r=0.27). According to the logistic regression model, there was a
      significant effect of the degenerative class on synovial levels of Coll2-1.
      CONCLUSIONS: Coll2-1 correlates well with the degenerative state of tarsocrural
      joints as evaluated by arthroscopy. This marker can therefore be classified as a
      burden-of-disease marker in the assessment of joint disease in horses.

PMID- 21884811
TI  - History of knee injuries and knee osteoarthritis: a meta-analysis of
      observational studies.
AB  - OBJECTIVES: Although knee injury has been implicated as a risk factor for the
      development of knee osteoarthritis (OA), there is great disparity in the
      magnitude of quantifiable risk. Our aim was to systematically review the
      relationship between history of knee injuries and knee OA. METHODS: Six
      electronic databases were searched between August and October 2010. Relative risk
      estimates or odds ratio (OR) and 95% confidence intervals (95% CI) were extracted
      or calculated from observational studies meeting the inclusion criteria.
      Publication bias was determined using funnel plot and the Egger's test.
      Heterogeneity was examined using Cochran Q test and I(2) statistic. Random
      effects model was used to pool the heterogeneous results and OR was used to
      present the results. Subgroup analyses were performed to examine potential causes
      of heterogeneity. RESULTS: Twenty-four observational studies (20,997 subjects)
      were included in the meta-analysis of which there were seven cohort, five cross
      sectional and 12 case-control studies. The overall pooled OR was 4.20 (95% CI
      3.11-5.66, I(2) = 81.0%). Association between history of knee injuries and knee
      OA was significantly different for specified injuries such as ligament or tendon
      injuries; meniscus damage or meniscectomy; and fracture of femur, knee or lower
      part of the leg (OR = 5.95, 95% 4.57-7.75), compared to unspecified injuries (OR
      = 3.12, 95% 2.17-4.50). CONCLUSION: History of knee injury is a major risk factor
      for the development of knee OA irrespective of study design and definition of
      knee injury. As one of the few modifiable/preventable risk factors, knee injury
      should be part of the future prevention programme in reducing the risk of knee
      OA.

PMID- 21884812
TI  - Association of vitamin D status with knee pain and radiographic knee
      osteoarthritis.
AB  - OBJECTIVE: The objective of the present study was to explore the association of
      serum vitamin D concentration and polymorphism in the vitamin D receptor (VDR),
      with knee pain and radiographic knee osteoarthritis (OA) among men and women in a
      large population-based UK cohort study. METHODS: Seven hundred and eighty-seven
      participants in the Hertfordshire Cohort Study (399 men, 388 women; mean age
      65.6+/-2.7 years) underwent a questionnaire on knee pain and radiographic knee
      examination. This study examined the association of Fok1, Cdx2 and Apa1
      polymorphism in the gene for the VDR and serum 25(OH)D concentration with knee
      pain and radiographic knee OA by a generalized estimating equations population
      averaged logistic regression analysis in the Hertfordshire Cohort Study. RESULTS:
      There were no associations of Fok1, Cdx2 and Apa1 polymorphisms of the VDR with
      knee OA except for Aa for Apa1 compared with AA [Odds ratio (OR) 0.59, 95%
      confidence interval (CI) 0.36-0.95, P=0.031]. While, ff for Fok1 (OR 1.60, 95% CI
      1.07-2.39, P=0.022) and AA for Cdx2 polymorphism (OR 2.21, 95% CI 1.07-4.56,
      P=0.032) was significantly associated with higher prevalence of knee pain
      compared with FF for Fok1 and GG for Cdx2, respectively. None of these are
      statistically significant after adjusting for the three polymorphisms tested.
      25(OH)D level was not significantly associated with radiographic knee OA, while,
      low tertile of 25(OH)D level tended to be associated with knee pain compared with
      high tertile of 25(OH)D level. CONCLUSION: The present cross-sectional study
      using a large-scale population from the Hertfordshire Cohort study indicated that
      vitamin D may be associated with pain rather than radiographic change, but the
      evidence for an association between vitamin D genetic variation and pain in knee
      OA is very weak in the present study. Further replication of our results will be
      required to elucidate the association of vitamin D and knee OA.

PMID- 21884814
TI  - Neuronal polarization and the cytoskeleton.
AB  - Neuronal polarization, the formation of one long axon and several short
      dendrites, is an obligatory process to integrate and propagate information within
      the brain. Axon formation is the key event during neuronal polarization and is
      based on tightly regulated rearrangements of the cytoskeleton. Here, we discuss
      how the cytoskeleton drives neuronal polarization. First, we convey the role of
      the actin cytoskeleton and microtubules during axon formation. Second, we discuss
      different cytoskeletal binding and regulating proteins, which are essential to
      specify the axon. Finally, we outline plus end tracking proteins (+TIPs) as
      important regulators for neuronal polarization by mediating the interaction
      between the actin cytoskeleton and microtubules and compare this function to
      other polarity processes.

PMID- 21884815
TI  - Bioenergetic components of reproductive effort in viviparous snakes: costs of
      vitellogenesis exceed costs of pregnancy.
AB  - Reproductive effort has been defined as the proportion of an organism's energy
      budget that is allocated to reproduction over a biologically meaningful time
      period. Historically, studies of reproductive bioenergetics considered energy
      content of gametes, but not costs of gamete production. Although metabolic costs
      of vitellogenesis (MCV) fundamentally reflect the primary bioenergetic cost of
      reproductive allocation in female reptiles, the few investigations that have
      considered costs of reproductive allocation have focused on metabolic costs of
      pregnancy (MCP) in viviparous species. We define MCP as energetic costs incurred
      by pregnant females, including all costs of maintaining gestation conditions
      necessary for embryogenesis. MCP by our definition do not include fetal costs of
      embryogenesis. We measured metabolic rates in five species of viviparous snakes
      (Agkistrodon contortrix, Boa constrictor, Eryx colubrinus, Nerodia sipedon, and
      Thamnophis sirtalis) during vitellogenesis and pregnancy in order to estimate MCV
      and MCP. Across all species, MCV were responsible for 30% increases in maternal
      metabolism. Phylogenetically-independent contrasts showed that MCV were
      significantly greater in B. constrictor than in other species, likely because B.
      constrictor yolk energy content was greater than that of other species. Estimates
      of MCP were not significantly different from zero in any species. In viviparous
      snakes, MCV appear to represent significant bioenergetic expenditures, while MCP
      do not. We suggest that MCV, together with yolk energy content, represent the
      most significant component of reptilian reproductive effort, and therefore
      deserve greater attention than MCP in studies of reptilian reproductive
      bioenergetics.

PMID- 21884816
TI  - Pharmacogenetics: past, present and future.
AB  - The subject area of pharmacogenetics, also known as pharmacogenomics, has a long
      history. Research in this area has led to fundamental discoveries, which have
      helped our understanding of the reasons why individuals differ in the way they
      handle drugs, and ultimately in the way they respond to drugs, either in terms of
      efficacy or toxicity. However, not much of this knowledge has been translated
      into clinical practice, most drug-gene associations that have some evidence of
      clinical validity have not progressed to clinical settings. Advances in genomics
      since 2000, including the ready availability of data on the variability of the
      human genome, have provided us with unprecedented opportunities to understand
      variability in drug responses, and the opportunity to incorporate this into
      patient care. This is only likely to occur with a systematic approach that
      evaluates and overcomes the different translational gaps in taking a biomarker
      from discovery to clinical practice. In this article, I explore the history of
      pharmacogenetics, appraise the current state of research in this area, and finish
      off with suggestions for progressing in the field in the future.

PMID- 21884813
TI  - 14-3-3 Proteins: diverse functions in cell proliferation and cancer progression.
AB  - The 14-3-3 proteins were the first phosphoserine/phosphothreonine-binding
      proteins to be discovered, a finding that provided the foundation for their
      prominent role in cell signaling. 14-3-3 family members interact with a wide
      spectrum of proteins including transcription factors, biosynthetic enzymes,
      cytoskeletal proteins, signaling molecules, apoptosis factors, and tumor
      suppressors. The interaction with 14-3-3 can have a profound effect on a target
      protein, altering its localization, stability, conformation, phosphorylation
      state, activity, and/or molecular interactions. Thus, by modulating the function
      of a diverse array of binding partners, 14-3-3 proteins have become key
      regulatory components in many vital cellular processes - processes that are
      crucial for normal growth and development and that often become dysregulated in
      human cancer. This review will examine the recent advances that further elucidate
      the role of 14-3-3 proteins in normal growth and cancer signaling with a
      particular emphasis on the signaling pathways that impact cell proliferation,
      cell migration, and epithelial-to-mesenchymal transition.

PMID- 21884817
TI  - Detailed characterization of alterations of chromosomes 7, 9, and 10 in
      glioblastomas as assessed by single-nucleotide polymorphism arrays.
AB  - Glioblastomas are cytogenetically heterogeneous tumors that frequently display
      alterations of chromosomes 7, 9p, and 10q. We used high-density (500K) single
      nucleotide polymorphism arrays to investigate genome-wide copy number alterations
      and loss of heterozygosity in 35 primary glioblastomas. We focused on the
      identification and detailed characterization of alterations involving the most
      frequently altered chromosomes (chromosomes 7, 9, and 10), the identification of
      distinct prognostic subgroups of glioblastomas based on the cytogenetic patterns
      of alteration for these chromosomes, and validation of their prognostic impact in
      a larger series of tumors from public databases. Gains of chromosome 7 (97%),
      with or without epidermal growth factor receptor (EGFR) amplification, and losses
      of chromosomes 9p (83%) and 10 (91%) were the most frequent alterations. Such
      alterations defined five different cytogenetic groups with a significant effect
      on patient survival; notably, EGFR amplification (29%) was associated with a
      better survival among older patients, as confirmed by multivariate analysis of a
      larger series of glioblastomas from the literature. In addition, our results
      provide further evidence about the relevance of other genes (eg, EGFR, CDKN2A/B,
      MTAP) in the pathogenesis of glioblastomas. Altogether, our results confirm the
      cytogenetic heterogeneity of glioblastomas and suggest that their stratification
      based on combined assessment of cytogenetic alterations involving chromosomes 7,
      9, and 10 may contribute to the prognostic evaluation of glioblastomas.

PMID- 21884818
TI  - A novel DHPLC-based procedure for the analysis of COL1A1 and COL1A2 mutations in
      osteogenesis imperfecta.
AB  - Approximately 90% of patients with osteogenesis imperfecta (OI) exhibit dominant
      COL1A1 or COL1A2 mutations; however, molecular analysis is difficult because
      these genes span 51 and 52 exons, respectively. We devised a PCR-denaturing high
      performance liquid chromatography (DHPLC) procedure to analyze the COL1A1 or
      COL1A2 coding regions and validated it using 130 DNA samples from individuals
      without OI, 25 DNA samples from two cells to investigate the procedure's
      potential for preimplantation diagnosis, and DNA samples from 10 patients with
      OI. Three novel intronic variants in vitro were expressed using a minigene assay
      to assess their effects on splicing. The procedure is rapid, inexpensive, and
      reproducible. Analysis of samples from individuals without OI revealed six novel
      and some known polymorphisms useful for linkage diagnosis because of high
      heterozygosity. Analysis of two-cell samples confirmed the known genotype in 24
      of 25 experiments; DNA failed to amplify in only one case. No incidence of allele
      dropout was recorded. DHPLC revealed six novel mutations, three of which were
      intronic, in all patients with OI, and these results were confirmed by means of
      COL1A1 and COL1A2 direct sequencing. Expression of intronic mutations
      demonstrated that variant 804 + 2_804 + 3delTG in intron 11 disrupts normal
      splicing, thereby leading to formation of two alternative products. Variants
      c.3046-4_3046-5dupCT (COL1A1) and c.891 + 77A>T (COL1A2) did not affect splicing.
      The described DHPLC protocol combined with the minigene assay may contribute to
      molecular diagnosis in OI. Moreover, this protocol will aid in counseling about
      prenatal and preimplantation diagnosis.

PMID- 21884819
TI  - Paraffin embedding contributes to RNA aggregation, reduced RNA yield, and low RNA
      quality.
AB  - The RNA isolated from FFPE tissues is of poor quality and quantity. Other studies
      have indicated that formaldehyde fixation or the duration of storage of tissue
      blocks accounted for RNA damage. Herein we report a third source of harm to RNA:
      embedding in warm paraffin. RNA bound to oligo(dT)-conjugated magnetic beads (an
      mRNA model) and total cellular RNA pellets were passed through formalin, graded
      ethanols, xylene, paraffin, and a formaldehyde demodification step. The mRNA
      model yielded at least 1550 bp amplicons at RT-PCR at each step of processing
      except paraffin, which yielded no more than 750 bp amplicons regardless of
      paraffin formulation or transition solvent. Quantitative RT-PCR on paraffinized
      RNA suggested a 1400-fold or more decrease in amplifiable RNA when compared with
      control. Compared with earlier processing steps, formalin-fixed paraffinized
      total cellular RNA produced only high-molecular-weight RNA and insoluble
      aggregates. These species were reproduced by heating RNA in hydrocarbon solvent
      at 60 degrees C for 1 hour. Quantitative RT-PCR on paraffinized RNA suggested an
      at least 10- to 160-fold decrease in amplifiable RNA compared to controls. The
      data implicate paraffin embedding as primarily responsible for the high-molecular
      weight RNA aggregates, reduced yields of RNA, and poor quality of RNA isolated
      from these chemical models of FFPE tissues.

PMID- 21884822
TI  - Neighborhood hash graph kernel for protein-protein interaction extraction.
AB  - Automated extraction of protein-protein interactions (PPIs) from biomedical
      literatures is an important topic of biomedical text mining. In this paper, we
      propose an approach based on neighborhood hash graph kernel for this task. In
      contrast to the existing graph kernel-based approaches for PPI extraction, the
      proposed approach not only has the capability to make use of full dependency
      graphs to represent the sentence structure but also effectively control the
      computational complexity. We evaluate the proposed approach on five publicly
      available PPI corpora and perform detailed comparisons with other approaches. The
      experimental result shows that our approach is comparable to the state-of-the-art
      PPI extraction system and much faster than all-path graph kernel approach on all
      five PPI corpora.

PMID- 21884821
TI  - Computer-based genealogy reconstruction in founder populations.
AB  - This paper describes a software tool that reconstructs entire genealogies from
      data collected from different and heterogeneous sources, including municipal and
      parish records archived over centuries. The tool exploits a record linkage
      algorithm relying on a rule-based data matching approach. It applies a general
      strategy for managing the ambiguities due to missing, imprecise or erroneous
      input data. The process follows an iterative approach that combines automatic
      pedigree reconstruction with software-empowered human data revision to improve
      the quality and the accuracy of the results and to optimize the matching rules.
      The paper discusses the results obtained by reconstructing the entire genealogy
      of the population of the Val Borbera, a geographically isolated valley in
      Northern Italy. The genealogy could be reconstructed from data going back as far
      as the XVI century. The resulting pedigree includes 75,994 trios, 58.9% of which
      belonging to a unique big family, reconstructed over 13 generations.

PMID- 21884820
TI  - Detection of KIAA1549-BRAF fusion transcripts in formalin-fixed paraffin-embedded
      pediatric low-grade gliomas.
AB  - Alterations of BRAF are the most common known genetic aberrations in pediatric
      gliomas. They frequently are found in pilocytic astrocytomas, where genomic
      duplications involving BRAF and the poorly characterized gene KIAA1549 create
      fusion proteins with constitutive B-Raf kinase activity. BRAF V600E point
      mutations are less common and generally occur in nonpilocytic tumors. The
      development of BRAF inhibitors as drugs has created an urgent need for robust
      clinical assays to identify activating lesions in BRAF. KIAA1549-BRAF fusion
      transcripts have been detected in frozen tissue, however, methods for FFPE tissue
      have not been reported. We developed a panel of FFPE-compatible quantitative RT
      PCR assays for the most common KIAA1549-BRAF fusion transcripts. Application of
      these assays to a collection of 51 low-grade pediatric gliomas showed 97%
      sensitivity and 91% specificity compared with fluorescence in situ hybridization
      or array comparative genomic hybridization. In parallel, we assayed samples for
      the presence of the BRAF V600E mutation by PCR pyrosequencing. The data further
      support previous observations that these two alterations of the BRAF, KIAA1549
      fusions and V600E point mutations, are associated primarily with pilocytic
      astrocytomas and nonpilocytic gliomas, respectively. These results show that
      fusion transcripts and mutations can be detected reliably in standard FFPE
      specimens and may be useful for incorporation into future studies of pediatric
      gliomas in basic science or clinical trials.

PMID- 21884823
TI  - Study of the adjuvanticity of lysine lipopeptides; carbamate analogs elicit
      strong Th1 and Th2 response to ovalbumin in mice.
AB  - Bacterial lipoproteins and their synthetic analogs are strong immune modulators
      of the early host responses. In view of the strong adjuvanticity of bacterial
      lipopeptide mimics bearing lysine residues, a focused library of lipidated
      dipeptides and tripeptides has been synthesized with a view to understand the
      pattern of activity vis a vis the site and extent of lipidation. Compounds 4, 5
      and 14 stimulate OVA specific IgG titer, neutralization of antibodies (IgG1 and
      IgG2a), T lymphocyte sub-sets (CD4/CD8) and its production of soluble mediators
      for Th1 (IFN-gamma)/Th2 (IL-4) cytokines and costimulatory molecules (CD80/CD86)
      which are ideal traits of immune adjuvants. The results support lipidated lysine
      dipeptides as potent enhancers of humoral and cell mediated immune responses and
      thus might become promising immune-adjuvants for self adjuvanted vaccines.

PMID- 21884824
TI  - Augmentation of humoral and cell mediated immune responses by Thujone.
AB  - Thujone, a naturally occurring monoterpene, was found to enhance the total WBC
      count, bone marrow cellularity, number of alpha-esterase positive cells, number
      of plaque forming cells in spleen and circulating antibody titer in Balb/c mice
      (1mg/kg body weight, intraperitoneally for 5 days). Thujone treatment enhanced
      proliferation of splenocytes and thymocytes, both in the presence and absence of
      specific mitogens. Administration of Thujone was found to stimulate the cell
      mediated immunological response in normal and tumor bearing Balb/c mice. A
      significant enhancement in natural killer (NK) cell mediated cytotoxicity,
      antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent complement
      mediated cytotoxicity (ACC) in both normal as well as tumor-bearing animals was
      observed after the administration of Thujone. Production of cytokines such as IL
      2 and IFN-gamma was significantly enhanced by the administration of Thujone. The
      stimulatory effect of Thujone on cytotoxic T lymphocyte (CTL) generation was
      determined by Winn's neutralization assay using CTL sensitive EL4 thymoma cells.
      Thujone treatment showed a significant increase in CTL production in both the in
      vivo and in vitro models, as indicated by a significant increase in the life span
      of tumor bearing animals. All these results indicate that administration of
      Thujone could enhance the immune response of mice. There was a significant
      reduction in solid tumor development, mediated by the presence of alert immune
      responses during Thujone administration.

PMID- 21884825
TI  - Toll-like receptors and diseases.

PMID- 21884826
TI  - Chemosensory control by commissural nucleus of the solitary tract in rats.
AB  - The commissural nucleus of the solitary tract (commNTS) is a main area that
      receives afferent signals involved in the cardiovascular and respiratory control
      like those related to chemoreceptor activation, however, the importance of the
      commNTS for the cardiorespiratory responses to chemoreceptor activation is still
      controversial. In the present study, we investigated the cardiorespiratory
      responses to hypoxia or hypercapnia in anesthetized and conscious rats treated
      with injections of the GABA-A agonist muscimol into the caudal portion of the
      commNTS. Male Holtzman rats (280-300 g) were used. In conscious rats that had a
      stainless steel cannula previously implanted into the commNTS, the injection of
      muscimol (2 mM) into the commNTS reduced the pressor response (16+/-2 mmHg, vs.
      saline: 36+/-3 mmHg) and the increase in ventilation (250+/-17 ml/min/kg, vs.
      saline: 641+/-28 ml/min/kg) produced by hypoxia (8-10% O(2)). In urethane
      anesthetized rats, the injection of muscimol into the commNTS eliminated the
      pressor response (5+/-2 mmHg, vs. saline: 26+/-5 mmHg) and the increase in
      phrenic nerve discharge (PND) (20+/-6%, vs. saline: 149+/-15%) and reduced the
      increase in splanchnic sympathetic nerve discharge (sSND) (93+/-15%, vs. saline:
      283+/-19% of baseline) produced by hypoxia. However, muscimol injected into the
      commNTS did not change hypercapnia (8-10% CO(2)) induced pressor response or the
      increase in the sSND or PND in urethane anesthetized rats or the increase in
      ventilation in conscious rats. The present results suggest that the
      cardiorespiratory responses to hypoxia are strongly dependent on the caudal
      portion of the commNTS, however, this area is not involved in the responses to
      hypercapnia.

PMID- 21884827
TI  - PLP-dependent enzymes as potential drug targets for protozoan diseases.
AB  - The chemical properties of the B(6) vitamers are uniquely suited for wide use as
      cofactors in essential reactions, such as decarboxylations and transaminations.
      This review addresses current efforts to explore vitamin B(6) dependent enzymatic
      reactions as drug targets. Several current targets are described that are found
      amongst these enzymes. The focus is set on diseases caused by protozoan
      parasites. Comparison across a range of these organisms allows insight into the
      distribution of potential targets, many of which may be of interest in the
      development of broad range anti-protozoan drugs. This article is part of a
      Special Issue entitled: Pyridoxal Phosphate Enzymology.

PMID- 21884828
TI  - Aggrecan, an unusual polyelectrolyte: review of solution behavior and
      physiological implications.
AB  - Aggrecan is a high-molecular-weight, bottlebrush-shaped, negatively charged
      biopolymer that forms supermolecular complexes with hyaluronic acid. In the
      extracellular matrix of cartilage, aggrecan-hyaluronic acid complexes are
      interspersed in a collagen meshwork and provide the osmotic properties required
      to resist deswelling under compressive load. In this review we compile aggrecan
      solution behavior from different experimental techniques, and discuss them in the
      context of concentration regimes that were identified in osmotic pressure
      experiments. At low concentrations, aggrecan exhibits microgel-like behavior.
      With increasing concentration, the bottlebrushes self-assemble into large
      complexes. In the physiological concentration range (2<c(aggrecan)<8% w/w), the
      physical properties of the solution are dominated by repulsive electrostatic
      interactions between aggrecan complexes. We discuss the consequences of the
      bottlebrush architecture on the polyelectrolyte characteristics of the aggrecan
      molecule, and its implications for cartilage properties and function.

PMID- 21884830
TI  - Modulation of osteogenic activity of BMP-2 by cellulose and chitosan derivatives.
AB  - Polysaccharides with structure and potential bioactivity similar to heparin were
      synthesized based on cellulose which was regioselectively sulfated, carboxylated
      or carboxymethylated, and chitosan that was sulfated only. Osteogenic activity of
      these derivatives was studied in cooperation with BMP-2 using C2C12 myoblast
      cells as a model system measuring alkaline phosphatase (ALP) activity and the
      expression of the genes Osterix, Noggin and Runx-2. It was found that highly
      sulfated chitosan showed the strongest osteogenic activity of all
      polysaccharides, but only at lower concentrations, while higher concentrations
      were inhibitory. By contrast, cellulose with a low or intermediate degree of
      sulfation showed increasing ALP activity and expression of Osterix and Noggin
      with rising concentrations. Lower sulfated cellulose with a high degree of
      carboxylation was less osteogenic, but had a positive effect on cell viability,
      while carboxymethylated cellulose had almost no osteogenic activity. The results
      indicate that regioselectively sulfated as well as carboxylated cellulose and
      chitosan possess an osteogenic activity, which makes them interesting candidates
      for application in tissue engineering of bone.

PMID- 21884829
TI  - Viscoelastic and biological performance of low-modulus, reactive calcium
      phosphate-filled, degradable, polymeric bone adhesives.
AB  - The aim of this study was to investigate the effect of reactive mono- and
      tricalcium phosphate addition on the mechanical, surface free energy, degradation
      and cell compatibility properties of poly(lactide-co-propylene glycol-co-lactide)
      dimethacrylate (PPGLDMA) thin films. Dry composites containing up to 70 wt.%
      filler were in a flexible rubber state at body temperature. Filler addition
      increased the initial strength and Young's modulus and reduced the elastic and
      permanent deformation under load. The polymer had high polar surface free energy,
      which might enable greater spread upon bone. This was significantly reduced by
      filler addition but not by water immersion for 7 days. The samples exhibited
      reduced water sorption and associated bulk degradation when compared with
      previous work with thicker samples. Their cell compatibility was also improved.
      Filler raised water sorption and degradation but improved cell proliferation. The
      materials are promising bone adhesive candidates for low-load-bearing areas.

PMID- 21884831
TI  - Submicron-textured biomaterial surface reduces staphylococcal bacterial adhesion
      and biofilm formation.
AB  - Staphylococci are among the most important pathogens causing bloodstream
      infections associated with implanted medical devices. Control of bacterial
      adhesion to material surfaces is important for prevention of biofilm formation
      and biomaterial-associated infections. In this study, we hypothesized that
      submicron (staphylococcal bacterial dimension) surface textures may reduce the
      bacterial adhesion via a decrease in surface area that bacteria can contact, and
      subsequently inhibit biofilm formation. Poly(urethane urea) films were textured
      with two different sizes of submicron pillars via a two-stage replication
      process. Adhesion of two bacterial strains (Staphylococcus epidermidis RP62A and
      S. aureus Newman) was assessed over a shear stress range of 0-13.2 dyn cm(-2)
      using a rotating disk system in physiological buffer solutions. Significant
      decreases in bacterial adhesion were observed on textured surfaces for both
      strains compared with smooth controls. Biofilm formation was further tested on
      surfaces incubated in solution for either 2 or 5 days and it was found that
      biofilm formation was dramatically inhibited on textured surfaces. The results of
      the approaches used in this work demonstrate that patterned surface texturing of
      biomaterials provides an effective means to reduce staphylococcal adhesion and
      biofilm formation on biomaterial surfaces, and thus to prevent biomaterial
      associated infections.

PMID- 21884832
TI  - A micropatterning and image processing approach to simplify measurement of
      cellular traction forces.
AB  - Quantification of the traction forces that cells apply to their surroundings has
      been critical to the advancement of our understanding of cancer, development and
      basic cell biology. This field was made possible through the development of
      engineered cell culture systems that permit optical measurement of cell-mediated
      displacements and computational algorithms that allow conversion of these
      displacements into stresses and forces. Here, we present a novel advancement of
      traction force microscopy on polyacrylamide (PAA) gels that addresses limitations
      of existing technologies. Through an indirect patterning technique, we generated
      PAA gels with fluorescent 1 MUm dot markers in a regularized array. This improves
      existing traction measurements since (i) multiple fields of view can be measured
      in one experiment without the need for cell removal; (ii) traction vectors are
      modeled as discrete point forces, and not as a continuous field, using an
      extremely simple computational algorithm that we have made available online; and
      (iii) the pattern transfer technique is amenable to any of the published
      techniques for producing patterns on glass. In the future, this technique will be
      used for measuring traction forces on complex patterns with multiple, spatially
      distinct ligands in systems for applying strain to the substrate, and in sandwich
      cultures that generate quasi-three-dimensional environments for cells.

PMID- 21884833
TI  - Influence of the pore generator on the evolution of the mechanical properties and
      the porosity and interconnectivity of a calcium phosphate cement.
AB  - Porosity and interconnectivity are important properties of calcium phosphate
      cements (CPCs) and bone-replacement materials. Porosity of CPCs can be achieved
      by adding polymeric biodegradable pore-generating particles (porogens), which can
      add porosity to the CPC and can also be used as a drug-delivery system. Porosity
      affects the mechanical properties of CPCs, and hence is of relevance for clinical
      application of these cements. The current study focused on the effect of
      combinations of polymeric mesoporous porogens on the properties of a CPC, such as
      specific surface area, porosity and interconnectivity and the development of
      mechanical properties. CPC powder was mixed with different amounts of PLGA
      porogens of various molecular weights and porogen sizes. The major factors
      affecting the properties of the CPC were related to the amount of porogen loaded
      and the porogen size; the molecular weight did not show a significant effect per
      se. A minimal porogen size of 40 MUm in 30 wt.% seems to produce a CPC with
      mechanical properties, porosity and interconnectivity suitable for clinical
      applications. The properties studied here, and induced by the porogen and CPC,
      can be used as a guide to evoke a specific host-response to maintain CPC
      integrity and to generate an explicit bone ingrowth.

PMID- 21884835
TI  - Non-invasive proteomic analysis of human skin keratins: screening of methionine
      oxidation in keratins by mass spectrometry.
AB  - Keratins are the main constituent of human skin and have been identified as major
      oxidative target proteins. However, there has been a lack of studies aimed at
      identifying the oxidation sites of keratins because of the difficulties
      associated with their insolubility and handling. Here, we introduce a mass
      spectrometry (MS)-based proteomic methodology to screen oxidative modifications
      in human skin keratins. Human skin proteins were obtained non-invasively by tape
      stripping and solubilized in SDS buffer, followed by purification and digestion
      using the modified filter-aided sample preparation method. The tryptic peptides
      were then analyzed by MALDI-TOF/MS, LC-ESI/MS, and MS/MS. PMF analyses have
      identified keratins K1 and K10 as the major proteins of human skin. Met(259),
      Met(262), Met(296), and Met(469), located in the alpha-helical rod domain of K1,
      were the most susceptible sites to oxidation induced by hydrogen peroxide in
      vitro and in vivo. Our results indicate a potential use of the identified
      methionine residues as biomarkers of oxidative skin damage. The present
      methodology is the first MS-based approach to detecting oxidative modifications
      in keratins obtained directly from human skin and can be easily applied to the
      monitoring of other keratin modifications in various skin conditions.

PMID- 21884834
TI  - Proteomic analysis of early response lymph node proteins in mice treated with
      titanium dioxide nanoparticles.
AB  - Human exposure to nanoparticles is inevitable from natural and anthropogenic
      sources. Titanium dioxide (TiO2) nanoparticles are increasingly being used in
      pharmaceutical and cosmetic products. Previous studies revealed that TiO2 levels
      were significantly increased in tissues (e.g., lymph nodes) after mice were
      injected with nanosized TiO2. To identify early response lymph node proteins to
      TiO2 nanoparticles, groups of mice were intradermally injected with a low dose of
      DeGussa P25 TiO2 nanoparticles or vehicle alone. The proteomes of lymph nodes at
      24 h were quantitatively analyzed using trypsin-catalyzed 16O/18O labeling in
      conjunction with two-dimensional liquid chromatography separation and tandem mass
      spectrometry (2DLC-MS/MS). A total of 33 proteins were significantly changed
      (over 1.3-fold, p<0.05) in the mice treated with TiO2 nanoparticles, which
      accounted for approximately 1% of the total proteins identified. The
      differentially expressed proteins mainly involve the immune response (e.g.,
      inflammation), lipid and fatty acid metabolism, mRNA processing, and nucleosome
      assembly. Regulation of functionally distinct classes of proteins could be
      mediated by estrogen receptor (ESR1), PPARgamma, and c-Myc signalings, etc. The
      differentially expressed proteins identified in this experiment could represent
      early response proteins to TiO2 nanoparticle treatment in mouse lymph nodes.

PMID- 21884836
TI  - The importance of murine cortical bone microstructure for microcrack initiation
      and propagation.
AB  - In order to better understand bone postyield behavior and consequently bone
      failure behavior, this study aimed first to investigate cortical bone
      microstructure and second, to relate cortical bone microstructure to microdamage
      initiation and propagation in C57BL/6 (B6) and C3H/He (C3H) mice; two murine
      inbred strains known for their differences in bone phenotype. Murine femora of B6
      and C3H were loaded axially under compression in a stepwise manner. For each
      loading step, 3D data sets at a nominal resolution of 700 nm were acquired by
      means of synchrotron radiation-based computed tomography. Cortical bone
      microstructure was divided into three phases: the canal network, the osteocyte
      lacunar system, and microdamage. Canal volume density and canal unit volume both
      correlated highly to crack number density (canal volume density: R(2)=0.64,
      p<0.005 and canal unit volume: R(2)=0.75, p<0.001). Moreover, the large canal
      units in C3H bone were responsible for more microdamage accumulation compared to
      B6 bones. This more pronounced microdamage accumulation due to large
      intracortical bone voids, which eventually leads to a fatal macrocrack
      (fracture), represents a potential contributing factor to the higher incidence of
      bone fractures in the elderly.

PMID- 21884838
TI  - Influencing safe perioperative practice through collaboration.

PMID- 21884837
TI  - TNFalpha inhibits the development of osteoclasts through osteoblast-derived GM
      CSF.
AB  - Inflammatory cytokines such as tumor necrosis factor-alpha (TNFalpha) are potent
      stimulators of osteoclast formation and bone resorption and are frequently
      associated with pathologic bone metabolism. The cytokine exerts specific effects
      on its target cells and constitutes a part of the cellular microenvironment.
      Previously, TNFalpha was demonstrated to inhibit the development of osteoclasts
      in vitro via an osteoblast-mediated pathway. In the present study, the molecular
      mechanisms of the inhibition of osteoclastogenesis were investigated in co
      cultures of osteoblasts and bone marrow cells (BMC) and in cultures of macrophage
      colony stimulating factor (M-CSF) dependent, non-adherent osteoclast progenitor
      cells (OPC) grown with M-CSF and receptor activator of NF-kappaB ligand (RANKL).
      Granulocyte-macrophage colony stimulating factor (GM-CSF), a known inhibitor of
      osteoclastogenesis was found to be induced in osteoblasts treated with TNFalpha
      and the secreted protein accumulated in the supernatant. Dexamethasone (Dex), an
      anti-inflammatory steroid, caused a decrease in GM-CSF expression, leading to
      partial recovery of osteoclast formation. Flow cytometry analysis revealed that
      in cultures of OPC, supplemented with 10% conditioned medium (CM) from
      osteoblasts treated with TNFalpha/1,25(OH)(2)D(3), expression of RANK and CD11c
      was suppressed. The decrease in RANK expression may be explained by the finding,
      that GM-CSF and the CM from wt osteoblasts were found to suppress the expression
      of c-Fos, Fra-1, and Nfatc-1. The failure of OPC to develop into CD11c(+)
      dendritic cells suggests that cell development is not deviated to an alternative
      differentiation pathway, but rather, that the monocytes are maintained in an
      undifferentiated, F4/80(+), state. The data further implies possible interactions
      among inflammatory cytokines. GM-CSF induced by TNFalpha acts on early
      hematopoietic precursors, inhibiting osteoclastogenesis while acting as the
      growth factor for M-CSF independent inflammatory macrophages. These in turn may
      condition a microenvironment enhancing osteoclast differentiation and bone
      resorption upon migration of the OPC from circulation to the bone/bone marrow
      compartment.

PMID- 21884839
TI  - Creating high reliability: a new approach for patient safety.

PMID- 21884840
TI  - Concerns raised about literature review on skin prep agents.

PMID- 21884841
TI  - Concerns raised about literature review on skin prep agents.

PMID- 21884843
TI  - Supply chain optimization for pediatric perioperative departments.
AB  - Economic challenges compel pediatric perioperative departments to reduce nonlabor
      supply costs while maintaining the quality of patient care. Optimization of the
      supply chain introduces a framework for decision making that drives fiscally
      responsible decisions. The cost-effective supply chain is driven by implementing
      a value analysis process for product selection, being mindful of product sourcing
      decisions to reduce supply expense, creating logistical efficiency that will
      eliminate redundant processes, and managing inventory to ensure product
      availability. The value analysis approach is an analytical methodology for
      product selection that involves product evaluation and recommendation based on
      consideration of clinical benefit, overall financial impact, and revenue
      implications.

PMID- 21884844
TI  - Implementation of an informational card to reduce family members' anxiety.
AB  - For surgical patients' family members, the wait during surgery can cause anxiety
      that can be exacerbated if staff members provide inadequate or inconsistent
      information about the patient's status. Educational interventions and other staff
      intensive measures to help reduce family members' anxiety can be time consuming
      for staff members and impractical in a high-volume facility. To improve
      communication with patients' families, nurses at a heart and vascular hospital in
      Dallas, Texas, designed and distributed a card containing estimated procedure
      times, helpful telephone numbers, and other information. A survey of family
      members indicated that receiving the card reduced anxiety in a significant
      proportion of the respondents.

PMID- 21884845
TI  - AORN ergonomic tool 7: pushing, pulling, and moving equipment on wheels.
AB  - Pushing and pulling equipment in and around the OR can place high shear force
      demands on perioperative team members' shoulder and back muscles and joints.
      These high forces may lead to work-related musculoskeletal disorders. AORN
      Ergonomic Tool 7: Pushing, Pulling, and Moving Equipment on Wheels can help
      perioperative team members assess the risk of pushing and pulling tasks in the
      perioperative setting. The tool provides evidence-based suggestions about when
      assistive devices should be used for these tasks and is based on current
      ergonomic safety concepts, scientific evidence, and knowledge of effective
      technology and procedures, including equipment and devices for safe patient
      handling.

PMID- 21884846
TI  - Communication in the perioperative setting.
AB  - Poor communication in the perioperative setting contributes to an unsafe OR
      culture and affects patient safety and employee engagement, decision making,
      productivity, morale, and retention. Communication breakdowns can lead to
      surgical delays, patient inconvenience, and serious errors. Simplification and
      standardization of communication processes and the use of effective communication
      skills (eg, clear verbal communication, awareness of the effects of nonverbal
      communication, use of listening and conflict management skills) are ways to
      improve OR interactions and minimize or prevent errors.

PMID- 21884847
TI  - Deployment to Afghanistan: perioperative nursing outside the comfort zone.
AB  - Multiple missions are assigned to the Bagram Airfield in Afghanistan, including
      providing combat medical and medical support services to US and coalition forces
      and providing resources to strengthen security and build a solid health care
      infrastructure. Craig Joint Theater Hospital located at Bagram Airfield is
      staffed primarily with Air Force personnel serving a six-month tour of duty. The
      three-suite OR is in operation 24 hours a day, seven days a week, as is the rest
      of the hospital. In 2009, health care providers at Craig Joint Theater Hospital
      treated the highest number of casualties in the history of the US involvement in
      the Afghanistan conflict. They assessed and categorized patients using the Injury
      Severity Score to evaluate the number and acuity of patients treated. During one
      nurse's deployment in 2009, practice challenges occurred daily and personnel
      quickly learned how to adapt using the resources available. In addition to
      regular perioperative duties, Bagram Airfield perioperative nurses mentored a
      number of Afghan physicians and nurses.

PMID- 21884848
TI  - Know your netiquette.

PMID- 21884849
TI  - New IAHCSMM loaner instrumentation position paper and policy template.

PMID- 21884850
TI  - Perioperative care of the patient with rheumatoid arthritis.

PMID- 21884851
TI  - Reducing the incidence of retained surgical instrument fragments.

PMID- 21884854
TI  - Are two insulin pumps better than one?

PMID- 21884855
TI  - The need for transformative innovation in hypertension management.
AB  - Despite multiple available effective therapies for hypertension, many patients
      with high blood pressure in the United States are not adequately controlled. This
      inability to effectively manage hypertension can be attributed to patient,
      provider, and system failures. To create an effective model for hypertension
      management, current care delivery systems must be reorganized around the
      following principles: improved patient engagement and patient-provider
      communication, increased use of nonphysician providers, better performance
      monitoring and feedback systems, and better aligned reimbursement models.
      Transformation of care around these principles would lead to marked improvements
      in cost, quality, and access to care.

PMID- 21884856
TI  - Medication adherence: a call for action.
AB  - Poor adherence to efficacious cardiovascular-related medications has led to
      considerable morbidity, mortality, and avoidable health care costs. This article
      provides results of a recent think-tank meeting in which various stakeholder
      groups representing key experts from consumers, community health providers, the
      academic community, decision-making government officials (Food and Drug
      Administration, National Institutes of Health, etc), and industry scientists met
      to evaluate the current status of medication adherence and provide
      recommendations for improving outcomes. Below, we review the magnitude of the
      problem of medication adherence, prevalence, impact, and cost. We then summarize
      proven effective approaches and conclude with a discussion of recommendations to
      address this growing and significant public health issue of medication
      nonadherence.

PMID- 21884857
TI  - Berlin Heart EXCOR Pediatric ventricular assist device Investigational Device
      Exemption study: study design and rationale.
AB  - BACKGROUND: Currently, there are no Food and Drug Administration-approved devices
      available that can provide long-term mechanical circulatory support to smaller
      children with severe heart failure as a bridge to heart transplant (HT). In
      recent years, the Berlin Heart EXCOR Pediatric ventricular assist device (VAD)
      has emerged as a potential treatment option. Systematic data on the safety and
      efficacy of the EXCOR are limited. METHODS: The Investigational Device Exemption
      (IDE) clinical study is designed to evaluate the safety and probable benefit of
      the EXCOR to support regulatory review of the device under the Humanitarian
      Device Exemption regulation. The study design and rationale are reviewed in light
      of the well-described challenges inherent in small population studies. RESULTS:
      The Berlin Heart EXCOR IDE clinical study is a prospective, multicenter, single
      arm, clinical cohort study. Children aged 0 to 16 years with severe heart failure
      (Interagency Registry for Mechanically Assisted Circulatory Support profile 1 or
      2) due to 2-ventricle heart disease and actively listed for HT comprise the
      primary study cohort. The control population is a propensity-matched
      retrospective cohort of children supported with extracorporeal membrane
      oxygenation, the only bridge device available to smaller children before the
      EXCOR. The primary efficacy end point is survival to heart transplantation or
      recovery. The primary safety end point is the incidence of serious adverse events
      as defined by pediatric Interagency Registry for Mechanically Assisted
      Circulatory Support criteria. The study will enroll a total of 48 subjects in 2
      cohorts based on body surface area (cohort 1 <0.7 m(2), cohort 2 0.7-1.5 m(2))
      and is powered to show safety superiority to a prespecified performance goal of
      0.25 serious adverse events per day of support. Children ineligible for the
      primary cohort will still have access to the device in a third compassionate-use
      cohort where adverse event data will be collected for additional safety
      characterization of the device. CONCLUSION: The Berlin Heart IDE clinical study
      will be the first bridge-to-HT VAD study designed exclusively for children. It is
      anticipated that the study will provide important information on the safety and
      efficacy of the Berlin Heart EXCOR Pediatric in children while providing valuable
      lessons into the design and conduct of future VAD studies in children.

PMID- 21884858
TI  - Mode of hospital presentation in patients with non-ST-elevation myocardial
      infarction: implications for strategic management.
AB  - INTRODUCTION: Contemporary non-ST-elevation myocardial infarction-acute coronary
      syndrome guidelines emphasize early-risk stratification and optimizing therapy
      including an invasive strategy in high-risk patients. To assess the feasibility
      of initiating this strategy in the prehospital environment, we examined how such
      patients are transported to hospital, their risk profile, and the proportion
      potentially eligible for such a strategy. METHODS: Consecutive patients with ST
      segment elevation myocardial infarction admitted in Edmonton were studied between
      September and November 2008 and divided according to their mode of transport to
      hospital: emergency medical services (EMS) versus self-presenting. Baseline
      characteristics, GRACE Risk Score, blinded core laboratory electrocardiogram
      analysis, cardiac biomarkers, in-hospital procedures, and outcomes were analyzed.
      RESULTS: Thirty-five percent (93/263) of patients presented via EMS and often to
      percutaneous coronary intervention hospitals, that is, 64.5% versus 44.1% (P =
      .0016). They were older (75 vs 62 years, P < .001), more often female (43% vs
      28.1%, P < .001), diabetic (34.4% vs 22.9%, P = .045), and hypertensive (72.0% vs
      57.1%, P = .017) and had higher GRACE Risk Scores (median 166 vs 130, P < .001).
      Electrocardiogram analysis revealed more baseline Q waves (38.8% vs 25.5%, P =
      .031) and ST depression >=2 mm (P = .027) in EMS-transported patients. Fewer EMS
      patients underwent cardiac catheterization (60.2% vs 88.2%, P < .001), and a
      paradoxical relationship existed between catheterization rates and GRACE Risk
      Score in the total cohort (low-risk: 93.4% vs high-risk: 59.3%, P < .001). The
      composite of death/re-myocardial infarction/congestive heart failure/shock was
      greater in EMS patients (unadjusted odds ratio 3.96, 95% CI 1.80-8.69, P = .001);
      these differences were attenuated after GRACE Risk Score adjustment. CONCLUSION:
      Regional strategies using risk-based triage, early medical therapy, and timely
      triage to percutaneous coronary intervention centers represents an unrealized
      opportunity to enhance ST-segment elevation myocardial infarction care.

PMID- 21884859
TI  - Trends in Q-wave acute myocardial infarction case fatality from 1978 to 2007 and
      analysis of the effectiveness of different treatments.
AB  - BACKGROUND: We sought to analyze the trends in first Q-wave acute myocardial
      infarction (AMI) case fatality from 1978 to 2007 in a population-based hospital
      register, to determine the variables related to these changes, and to assess the
      effectiveness of current AMI management. METHODS: Population-based hospital
      registry included patients with first Q-wave AMI aged 25 to 74 years admitted
      between 1978 and 2007. Sociodemographic and clinical characteristics, treatments,
      and procedures used during hospital stay, and 28-day case fatality were recorded.
      Logistic regression was used for multivariate analysis of six 5-year periods.
      RESULTS: The 30-year study included 3,982 patients. Mean 28-day case fatality was
      8.96%, with a decreasing trend from 16.6% in the first 5-year period to 4.7% in
      the sixth (P for trend < .001). Study period was independently associated with
      case fatality. Case-fatality reduction attributable to pharmacologic treatments
      was 51% overall; in 24-hour survivors, pharmacologic treatments and broad use of
      invasive procedures explained 39% and 38%, respectively, of the difference
      between the observed case fatality in 2003-2007 and 1978-1982. CONCLUSION: A
      dramatic decrease in 28-day case fatality occurred during this 30-year period and
      was mainly related to the use of antiplatelet drugs, beta-blockers, thrombolysis,
      and invasive procedures. These data support the current guidelines for the
      management of acute coronary syndrome.

PMID- 21884860
TI  - Temporal changes in emergency department triage of patients with acute myocardial
      infarction and the effect on outcomes.
AB  - BACKGROUND: All patients who present to an emergency department (ED) are triaged.
      The ED triage score may determine when patients are seen by a physician. Half of
      patients with acute myocardial infarction (AMI) were given a low priority score
      in Ontario in 2000/2001. We assessed the appropriateness of ED triage and its
      association with quality indicators and outcomes in a more recent AMI cohort and
      compared this with previous findings. METHODS: We conducted a retrospective
      cohort study of a population-based cohort of patients with AMI admitted to 96
      hospitals in Ontario, Canada, in 2004/2005. Outcome measures included rate of low
      priority ED triage (score of 3, 4, or 5), compared with an earlier cohort (fiscal
      year 2000) at the same sites, and the adjusted effect of low-priority ED triage
      on door-to-electrocardiogram, door-to-needle, and door-to-balloon time; hospital
      length of stay (LOS); and mortality. RESULTS: Among 6,605 patients with AMI, low
      priority triage was less frequent than in the earlier cohort, at 33.3% versus
      50.3%. In patients with ST-segment elevation myocardial infarction (STEMI), it
      was 25.9%, versus 43.8% previously. Between cohorts, the greatest improvement in
      triage occurred in patients with chest pain, in those seen at higher AMI volume
      EDs, and in ambulatory patients; patients seen at low AMI volume EDs, those with
      diabetes, and the elderly showed the least improvement. Being assigned a low
      priority triage score was associated with an adjusted increase in median door-to
      electrocardiogram and door-to-needle time of 12.2 (P < .001) and 20.7 minutes (P
      < .001), respectively, longer than in the earlier cohort (4.4 and 15.1 minutes).
      It was associated with hospital LOS >75th percentile (odds ratio [OR] 1.25, P <
      .001), and higher 90-day (OR 1.50, P = .02) and 1-year mortality (OR 1.37, P =
      .05) in patients with STEMI. CONCLUSION: Emergency department triage of patients
      with AMI improved substantially over 5 years. For the third of patients with AMI
      who continue to receive a low priority score, including 25% of patients with
      STEMI, the associated delays in diagnosis and therapy were greater than
      previously and were associated with increased hospital LOS and mortality. Given
      the impact of this initial, cursory assessment, hospital systems should consider
      monitoring the quality of their ED triage.

PMID- 21884861
TI  - Does subclinical atherosclerosis burden identify the increased risk of
      cardiovascular disease mortality among United Kingdom Indian Asians? A population
      study.
AB  - BACKGROUND: Indian Asians living in the United Kingdom have a >50% higher risk of
      cardiovascular disease (CVD) death compared with native European whites. The
      mechanisms underlying their excess mortality are not clear, and there are no
      validated tools capable of identifying this increased risk. The burden of
      subclinical atherosclerosis detected in the carotid arteries is an established
      prognosticator for major CVD events. We hypothesized that the increased
      prevalence of CVD among Indian Asians would be reflected by their having a
      greater burden of subclinical carotid artery atherosclerosis compared with
      European whites. METHODS: We studied 2,288 healthy subjects and 148 patients with
      known CVD from the London Life Sciences Prospective Population study who
      underwent carotid ultrasonography for assessment of intima-media thickness (IMT),
      plaque prevalence, and plaque echogenicity. RESULTS: The prevalence of CVD was
      significantly higher among Indian Asians compared with European whites (odds
      ratio 1.72, 95% CI 1.2-2.3). Intima-media thickness was slightly higher in
      European whites compared with that of Indian Asians (0.66 vs 0.65 mm, P = .06),
      reflecting their higher Framingham Risk Score. After adjustment for
      cardiovascular risk factors, there were no significant differences in IMT, plaque
      prevalence, or plaque echogenicity between the 2 ethnic groups regardless of CVD
      status. CONCLUSION: The burden of carotid atherosclerosis does not identify the
      markedly increased risk of CVD among United Kingdom Indian Asians. Other markers
      and mechanisms of disease require investigation in this high-risk group.

PMID- 21884862
TI  - Circulating levels of biomarkers of collagen synthesis and ventricular function
      and dyssynchrony in adolescents and young adults after repair of tetralogy of
      Fallot.
AB  - BACKGROUND: Circulating carboxy-terminal propeptide of type I procollagen (PICP)
      and amino-terminal propeptide of type III procollagen (PIIINP) are biomarkers of
      collagen synthesis. We tested the hypothesis that circulating PICP and PIIINP are
      altered and may correlate with ventricular volume load and function in patients
      with repaired tetralogy of Fallot (TOF). METHODS AND RESULTS: Serum PICP and
      plasma PIIINP levels were determined in 39 patients with repaired TOF aged 17.7
      +/- 4.1 years and 25 healthy controls and correlated with right ventricular (RV)
      and left ventricular (LV) volumes, functional indices, and mechanical
      dyssynchrony as assessed by 3-dimensional and tissue Doppler echocardiography.
      Compared with controls, patients had significantly higher circulating PICP (P =
      .016) and PIIINP (P = .008) levels, worse RV function with intra-RV mechanical
      delay (all P < .001), impaired LV systolic functional indices (all P < .05), and
      greater LV systolic dyssynchrony index (SDI) (P < .001). For the whole cohort,
      circulating PICP and PIIINP levels correlated with age (P = .001 and P < .001,
      respectively), body mass index (P = .033 and P = .012, respectively), LV
      eccentricity (P = .035 and P = .046, respectively), RV end-diastolic volume (P =
      .029 and P = .047, respectively), and LV SDI (both P < .001). In addition, PICP
      levels correlated negatively with RV and LV isovolumic acceleration and RV
      ejection fraction. Multiple linear regression analysis identified LV SDI as a
      significant independent correlate of circulating levels of PICP (beta = .31, P =
      .045) and PIIINP (beta = .37, P = .004). CONCLUSION: Circulating levels of PICP
      and PIIINP correlate positively with LV mechanical dyssynchrony in patients after
      TOF repair, implicating a possible role of increased collagen synthesis in its
      pathogenesis.

PMID- 21884863
TI  - Susceptibility to acute thoracic aortic dissections in patients dying outside the
      hospital: an autopsy study.
AB  - BACKGROUND: The objectives of this study were to identify the incidence and
      predictors of death from acute thoracic aortic dissections (AoDs) and to describe
      their associated clinical findings. METHODS: We analyzed the clinical and
      pathologic data from 141 consecutive autopsies of individuals with sudden death
      due to AoDs in Harris County, TX, from 2003 to 2010, which represented 20%
      (107/534) of all deaths attributed to AoDs during this period by the Texas
      Department of Health. Multivariate Cox regression was used to identify predictors
      of survival adjusting for differences in demographic and clinical
      characteristics. RESULTS: During the study period, 141 of 145 fatal victims of
      acute thoracic dissections underwent a full autopsy and were included in the
      analysis. In 84% of cases, death was caused by pericardial tamponade from
      ascending AoD. The frequency of deaths showed seasonal variation with peak
      incidence in the winter months. Compared with patients presenting to hospitals
      with AoD, individuals dying outside the hospital were more likely to be female,
      African American, younger than 50 years and to have had prior aortic disease. One
      third of subjects with AoD had seen a physician within 1 week of sudden death.
      The most consistent pathologic abnormality was marked ventricular hypertrophy
      (257 g/m(2) on average) out of proportion to expected values for age, gender, and
      body size. Hispanic patients and patients with congenital disorders, such as
      bicuspid aortic valve and Marfan syndrome, were significantly more likely to die
      of AoD at a younger age (38% vs 13%, P < .002). CONCLUSIONS: Our findings
      identify differences between patients hospitalized for AoD versus those who died
      without being hospitalized. Previously unreported vulnerabilities to sudden death
      from AoD in minority populations, specifically Hispanics, were also identified
      that merit follow-up in prospective studies.

PMID- 21884864
TI  - Diabetes, quality of care, and in-hospital outcomes in patients hospitalized with
      heart failure.
AB  - BACKGROUND: Diabetes mellitus is frequently comorbid with heart failure (HF). It
      is unclear if comorbid diabetes is associated with quality of care and in
      hospital mortality. METHODS: We analyzed 133,971 HF admissions from 431 hospitals
      between January 2005 and January 2010 comparing patients with and without
      diabetes. RESULTS: There were 54,352 (41%) patients hospitalized with HF with a
      history or newly diagnosed diabetes. After adjustment, patients with diabetes
      were as likely as patients without diabetes to appropriately receive the
      composite of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker
      and beta-blockers (odds ratio [OR] 0.99, 95% CI 0.94-1.04), angiotensin
      converting enzyme inhibitor/angiotensin receptor blocker (OR 0.98, 95% CI 0.92
      1.05), evidence-based beta-blockers (OR 1.04, 95% CI 0.98-1.1), and
      hydralazine/nitrates (OR 1.09, 95% CI 0.99-1.2). However, patients with diabetes
      were less likely to receive smoking cessation counseling (OR 0.89, 95% CI 0.81
      0.98) and blood pressure control (OR 0.81, 95% CI 0.78-0.84) and to attain the
      all-or-none composite measure (OR 0.96, 95% CI 0.93-0.99). Patients with diabetes
      were more likely to receive an aldosterone antagonist for reduced left
      ventricular ejection fraction (OR 1.05, 95% CI 1.00-1.11), lipid-lowering agent
      (OR 1.33, 95% CI 1.26-1.41), and influenza vaccination (OR 1.05, 95% CI 1.01
      1.09). Diabetes was independently associated with longer hospital stay but not
      within-hospital mortality. CONCLUSIONS: With few exceptions, the application of
      evidence-based care and in-hospital outcomes were similar whether or not diabetes
      was present in this large contemporary cohort of patients hospitalized with HF.

PMID- 21884865
TI  - Prognostic value of renin and prorenin in heart failure patients with decreased
      kidney function.
AB  - BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) plays a key role in
      the progression of heart failure (HF) and concomitant kidney dysfunction. Despite
      the use of RAAS blockade, sustained activation of RAAS has been suggested to link
      with adverse outcome. We aimed to investigate the prognostic value of active
      plasma renin concentration (APRC) and prorenin in patients with HF treated with
      RAAS-blocking agents and its relationship with kidney function parameters.
      METHODS: One hundred clinically stable patients with HF, treated with RAAS
      blocking agents, were studied. Renal function parameters including effective
      renal plasma flow and glomerular filtration rate were measured invasively. The
      combined end point consisted of all-cause mortality, heart transplantation, and
      admission to hospital for HF. RESULTS: Mean age was 58 +/- 12 years, and 76% were
      men. Mean left ventricular ejection fraction was 28 +/- 9, and median APRC levels
      were 24.3 ng/mL per hour. Active plasma renin concentration was most strongly
      associated with mean arterial pressure (r = 0.60, P < .001). In multivariate
      linear regression analysis, age, mean arterial pressure, angiotensin II
      concentration, and use of aldosterone antagonists were significantly related with
      APRC (adjusted R(2) = 0.53). Patients in the highest quartile of APRC had a worse
      prognosis. In multivariate analysis, APRC remained associated with worse
      prognosis: HR 2.87 (95% CI 1.14-7.20), P = .025. Prorenin did not show prognostic
      value. The prognostic value of APRC was strongest in patients with decreased
      kidney function. CONCLUSIONS: Our data indicate that APRC is a strong prognostic
      factor in patients with HF in the presence of RAAS inhibition, especially in
      patients with kidney dysfunction.

PMID- 21884866
TI  - The effect of bivalirudin on costs and outcomes of treatment of ST-segment
      elevation myocardial infarction.
AB  - BACKGROUND: Bivalirudin is commonly used during percutaneous coronary
      intervention (PCI) rather than unfractionated heparin. The higher cost of
      bivalirudin may be offset if it reduces costly bleeding complications and/or
      length of stay. We sought to assess the effect of using bivalirudin on the costs
      of care among patients with ST-segment elevation myocardial infarction (STEMI)
      undergoing PCI. METHODS: We analyzed data from 64,872 patients treated in 1 of
      278 hospitals. The effect of overall hospital use of bivalirudin on clinical and
      economic outcomes was assessed using multivariable regression, based on average
      hospital use of treatments. RESULTS: The use of bivalirudin among patients with
      STEMI treated with PCI varied widely across hospitals, with a median of 6.9%
      (interquartile range 2.3%-18.6%). After controlling for patient and hospital
      characteristics, use of bivalirudin rather than heparin and a glycoprotein
      IIb/IIIa inhibitor reduced bleeding (odds ratio 0.47, P < .001), length of stay (
      0.47 days, P < .03), and hospital costs (-14%, P < .04). CONCLUSIONS: Use of
      bivalirudin among patients with STEMI treated with PCI appears to reduce bleeding
      and overall costs.

PMID- 21884867
TI  - Altered health status and quality of life in South Asians with coronary artery
      disease.
AB  - BACKGROUND: People of South Asian (SA) ancestry are susceptible to coronary
      artery disease (CAD). Although studies suggest that SA with CAD has a worse
      prognosis compared with Europeans, it is unknown whether corresponding
      differences in functional status and quality-of-life (QOL) measures exist.
      Accordingly, we compared symptoms, function, and QOL in SA and European Canadians
      with CAD using the Seattle Angina Questionnaire (SAQ). METHODS: Using the Alberta
      Provincial Project for Outcomes Assessment in Coronary Heart Disease, an outcomes
      registry that captures patients undergoing cardiac catheterization in Alberta,
      Canada, we identified 635 SA and 18,934 European patients with angiographic CAD
      from January 1995 to December 2006 who reported health status outcomes using the
      SAQ at 1 year after the index catheterization. To obtain comparable clinical
      variables among SA and Europeans, we used a propensity score-matching technique.
      RESULTS: One-year adjusted mean (SD) scores were significantly lower in SA
      compared with European Canadians for most SAQ domains: exertional capacity (75
      [23] vs 80 [23], P = .011), anginal stability (77 [28] vs 77 [27], P = .627),
      anginal frequency (86 [23] vs 88 [20], P < .001), treatment satisfaction (86 [19]
      vs 89 [16], P < .001), and SAQ QOL (71 [24] vs 76 [21], P < .001). These results
      could not be accounted for by differences in baseline QOL scores or changes in
      health status from baseline to 1 year. CONCLUSION: South Asian Canadians with
      established CAD have significantly worse health status outcomes at 1 year after
      angiography compared with European Canadians. Further studies are warranted to
      improve functional outcomes in SA with CAD.

PMID- 21884868
TI  - Effects of verbal suggestion on coronary arteries: results of a randomized
      controlled experimental investigation during coronary angiography.
AB  - BACKGROUND: Decrease of chest pain perception under placebo conditions has been
      frequently observed. The aim of this study was to examine whether placebo-induced
      chest pain improvement could be the result of changes in coronary blood flow. We,
      therefore, performed an experiment to investigate whether a verbal suggestion
      (VS) integrated in a cardiologic procedure has an impact on diameters of coronary
      arteries. METHODS: A total of 30 chest pain patients with normal diagnostic
      angiograms were assigned to a VS or a control group (CG). Saline solution was
      administered intracoronarily to both groups. The VS group received a standardized
      VS, implying coronary vasodilation. The CG remained without VS. Coronary end
      points were the changes in percentage diameter stenosis, Minimal lumen diameter
      and reference diameter of the index coronary segment before and 60 seconds after
      the administration of saline. Furthermore, changes in hemodynamics, psychological
      distress, and chest pain perception were recorded. RESULTS: The VS led to
      coronary vasoconstriction in comparison with CG (change in mean percentage
      diameter stenosis +/- SD 3.2% +/- 6.3% vs -1.7% +/- 6.8%, P = .062; change in
      mean minimal lumen diameter +/- SD -0.18 +/- 0.32 mm vs 0.06 +/- 0.23 mm, P =
      .029, no relevant change in the reference diameter). At the same time, the degree
      of chest pain perception was significantly reduced in the VS group (-0.7 +/- 1.3)
      compared with the CG (0.3 +/- 1.3), P = .024. CONCLUSION: The findings of this
      study suggest that a VS results in a biological alteration within coronary
      arteries. Contrary to expectation, the VS led to vasoconstriction, whereas chest
      pain perception decreased.

PMID- 21884869
TI  - Association of health insurance status with presentation and outcomes of coronary
      artery disease among nonelderly adults undergoing percutaneous coronary
      intervention.
AB  - OBJECTIVE: The aim of this study was to determine if insurance status is
      associated with adverse outcomes in patients with coronary artery disease.
      METHODS: A cohort of 13,456 patients who underwent percutaneous coronary
      intervention (PCI) between January 1, 2004, and December 31, 2007, at 4 New York
      State teaching hospitals was retrospectively studied. The primary outcome of
      interest was in-hospital mortality from any cause. RESULTS: Of the 13,456
      patients studied, 11,927 (88.6%) were insured by private carriers, 1,036 (7.7%)
      patients were covered by Medicaid, and 493 (3.7%) were uninsured. Uninsured and
      Medicaid patients tended to be younger and more often nonwhite and Hispanic. They
      had a higher prevalence of congestive heart failure and worse left ventricular
      function. Compared with privately insured patients, uninsured and Medicaid
      patients had increased all-cause mortality (1.2% and 0.9%, respectively, vs 0.3%;
      P < .001). For all patients, lack of insurance (OR 3.02, 95% CI 1.10-8.28) and
      Medicaid (OR 4.39, 95% CI 1.93-9.99) were independently associated with
      mortality. Lack of insurance (OR 5.02, 95% CI 1.58-15.93) and Medicaid (OR 4.55,
      95% CI 1.19-17.45) were also independently associated with increased mortality in
      patients undergoing emergent PCI. CONCLUSION: Lack of insurance and Medicaid
      insurance are both independently associated with an increased risk of in-hospital
      mortality after PCI for coronary artery disease.

PMID- 21884870
TI  - Impact of smoking on antiplatelet effect of clopidogrel and prasugrel after
      loading dose and on maintenance therapy.
AB  - BACKGROUND: Pharmacodynamic studies reported an amplified on-clopidogrel platelet
      inhibition in smokers potentially caused by an increased metabolic drug
      activation via induction of cytochrome P450 1A2. The aims of this analysis were
      to evaluate the impact of smoking on the antiplatelet effect of clopidogrel and
      prasugrel and to test the potential interaction of smoking with the treatment
      effect of these drugs. METHODS: A variety of platelet function results was
      analyzed from 2 large cohorts of patients undergoing coronary intervention after
      loading with clopidogrel 600 mg (n = 2,533 and n = 1,996), a cohort of patients
      undergoing dose adaptation from 75 to 150 mg according to response to clopidogrel
      (n = 117) and a crossover trial comparing clopidogrel 150 mg with prasugrel 10 mg
      (n = 87). Linear regression analyses were used to test the impact of smoking on
      platelet function and to identify independent predictors of on-treatment platelet
      reactivity. The potential interaction of smoking with the clinical effect of
      clopidogrel versus prasugrel was analyzed in the TRITON-TIMI 38 cohort (n =
      13,608). RESULTS: No significant association of smoking with platelet reactivity
      on clopidogrel was seen in unadjusted and adjusted analyses. The variables most
      consistently associated with on-clopidogrel platelet function were age, sex,
      diabetes, and body mass index. There was no significant interaction of smoking
      status at presentation with the clinical efficacy of prasugrel versus clopidogrel
      (P for interaction = .39). CONCLUSIONS: Smoking does not impact on platelet
      reactivity in patients after loading or on different maintenance doses of
      clopidogrel. The clinical treatment effect of clopidogrel versus prasugrel is not
      affected by smoking status at presentation.

PMID- 21884871
TI  - Colchicine prevents early postoperative pericardial and pleural effusions.
AB  - BACKGROUND: No preventive pharmacologic strategies have been proven efficacious
      for the prevention of postoperative effusions after cardiac surgery. Colchicine
      is safe and efficacious for the prevention of pericarditis. On this basis, we
      realized a substudy of the COPPS trial to assess the efficacy and safety of
      colchicine for the prevention of postoperative pericardial and pleural effusions.
      METHODS: The COPPS is a multicenter, double-blind, randomized trial, where 360
      consecutive patients (mean age 65.7 +/- 12.3 years, 66% men), 180 in each
      treatment arm, were randomized on the third postoperative day to receive placebo
      or colchicine for 1 month (1.0 mg twice daily for the first day, followed by a
      maintenance dose of 0.5 mg twice daily in patients >=70 kg, and halved doses for
      patients <70 kg). The incidence of postoperative effusions was evaluated in each
      study group. RESULTS: Despite similar baseline features, colchicine significantly
      reduced the incidence of postoperative pericardial (12.8% vs 22.8%, P = .019,
      relative risk reduction 43.9%, no. of patients needed to treat 10) and pleural
      effusions (12.2% vs 25.6%, P = .002, relative risk reduction 52.3%, no. of
      patients needed to treat 8). The rate of side effects (only gastrointestinal
      intolerance) and drug withdrawal was similar in the study groups with a trend
      toward an increased rate of both events for colchicine. In multivariable
      analysis, female gender (hazard ratio 1.76, 95% CI 1.03-3.03, P = .040) and
      pleura incision (hazard ratio 2.58, 95% CI 1.53-4.53, P < .001) were risk factors
      for postoperative effusions. CONCLUSIONS: Colchicine is safe and efficacious for
      the primary prevention of postoperative effusions after cardiac surgery.

PMID- 21884872
TI  - Funding source and author affiliation in TASER research are strongly associated
      with a conclusion of device safety.
AB  - BACKGROUND: Controversy exists regarding the safety of electrical stun guns
      (TASERs). Much of the research on TASERs is funded by the maker of the device
      and, therefore, could be biased. We sought to determine if funding source or
      author affiliation is associated with TASER research conclusions. METHODS:
      MEDLINE was searched for TASER or electrical stun gun to identify relevant
      studies. All human and animal studies published up to September 01, 2010, were
      included. Reviews, editorials, letters, and case reports were excluded from the
      analysis. Two independent reviewers blinded to this study hypothesis evaluated
      each article with regard to conclusions of TASER safety. RESULTS: Fifty studies
      were reviewed: 32 (64%) were human studies and 18 (36%) were animal studies.
      Twenty-three (46%) studies were funded by TASER International or written by an
      author affiliated with the company. Of these, 22 (96%) concluded that TASERs are
      unlikely harmful (26%) or not harmful (70%). In contrast, of the 22 studies not
      affiliated with TASER, 15 (55%) concluded that TASERs are unlikely harmful (29%)
      or not harmful (26%). A study with any affiliation with TASER International had
      nearly 18 times higher odds to conclude that the TASER is likely safe as compared
      with studies without such affiliation (odds ratio 17.6, 95% CI 2.1-150.1, P =
      .001). CONCLUSIONS: Studies funded by TASER and/or written by an author
      affiliated with the company are substantially more likely to conclude that TASERs
      are safe. Research supported by TASER International may thus be significantly
      biased in favor of TASER safety.

PMID- 21884874
TI  - Clinical significance of late high-degree atrioventricular block in patients with
      left ventricular dysfunction after an acute myocardial infarction--a Cardiac
      Arrhythmias and Risk Stratification After Acute Myocardial Infarction (CARISMA)
      substudy.
AB  - BACKGROUND: High-degree atrioventricular block (HAVB) is a frequent complication
      in the acute stages of a myocardial infarction associated with an increased rate
      of mortality. However, the incidence and clinical significance of HAVB in late
      convalescent phases of an AMI is largely unknown. The aim of this study was to
      assess the incidence and prognostic value of late HAVB documented by continuous
      electrocardiogram (ECG) monitoring in post-AMI patients with reduced left
      ventricular function. METHODS: The study included 286 patients from the CARISMA
      study with AMI and left ventricular ejection fraction of 40% or less. An
      insertable loop recorder was implanted 5 to 21 days after AMI for incessant
      arrhythmia surveillance. Furthermore, ECG documentation was supplemented by a 24
      hour Holter monitoring conducted at week 6 post-AMI. The clinical significance of
      HAVB occurring more than 21 days after AMI was examined with respect to
      development of major heart failure events and major ventricular tachyarrhythmic
      events. RESULTS: During a median follow-up of 1.9 years (interquartile range 0.9
      2.0), late HAVB was documented in 30 patients. The risk of major heart failure
      events (hazard ratio [HR] 4.08 [1.38-12.09], P = .01) and major ventricular
      tachyarrhythmic events (HR = 5.41 [1.88-15.58], P = .002) were significantly
      increased in patients who developed late HAVB. CONCLUSION: High-degree
      atrioventricular block documented by continuous ECG monitoring occurring more
      than 3 weeks after AMI is a frequent complication in post-AMI patients with left
      ventricular dysfunction. Furthermore, HAVB is associated with ominous prognostic
      implications of both potentially lethal arrhythmias and heart failure.

PMID- 21884873
TI  - Vitamin D status is not related to development of atrial fibrillation in the
      community.
AB  - BACKGROUND: Atrial fibrillation (AF) is common and is an important cause of
      cardiovascular morbidity and mortality. Vitamin D is an emerging risk factor in
      cardiovascular disease, and vitamin D status is modifiable. Thus, we sought to
      investigate whether vitamin D status predisposed to the development of AF in a
      community-based sample. METHODS: We evaluated the relation between vitamin D
      status and development of AF in 2,930 participants of the Framingham Heart Study,
      Massachusetts, USA, without prevalent AF. The mean age was 65 +/- 11 years, and
      56% were women. Vitamin D status was assessed by measuring 25-hydroxyvitamin D
      (25[OH]D) concentrations. Multivariable Cox regression models were adjusted for
      AF risk factors and season. RESULTS: During a mean follow-up of 9.9 years, 425
      participants (15%) developed AF. In Cox proportional hazards models, 25(OH)D was
      not associated with development of AF, with a multivariable-adjusted hazard ratio
      of 0.99 per SD increment in 25(OH)D levels (95% CI 0.88-1.10, P = .81). Also, no
      relation was found in models including 25(OH)D as a dichotomous variable (above
      and below the cohort-specific 20th percentile; P = .59). CONCLUSION: In our
      community-based sample, vitamin D status was not related to incident AF. Our data
      suggest that vitamin D deficiency does not promote the development of AF in the
      ambulatory setting.

PMID- 21884875
TI  - Prognostic assessment of estimated glomerular filtration rate by the new Chronic
      Kidney Disease Epidemiology Collaboration equation in comparison with the
      Modification of Diet in Renal Disease Study equation.
AB  - BACKGROUND: Systematic reporting of estimated glomerular filtration rate (eGFR)
      using the Modification of Diet in Renal Disease (MDRD) Study equation is
      recommended for detection of chronic kidney disease and prediction of
      cardiovascular (CV) risk. The Chronic Kidney Disease Epidemiology Collaboration
      (CKD-EPI) equation is a newly developed and validated formula for eGFR that is
      more accurate at normal or near-normal eGFR. We aimed to assess the incremental
      prognostic accuracy of eGFR(CKD-EPI) versus eGFR(MDRD) in subjects at increased
      risk for CV disease. METHODS: We performed a post hoc analysis of the VALIANT
      trial that enrolled 14,527 patients with acute myocardial infarction with signs
      and symptoms of heart failure and/or left ventricular systolic dysfunction. The
      eGFR(MDRD) and eGFR(CKD-EPI) were computed using age, gender, race, and baseline
      creatinine level. Patients were categorized according to their eGFR using each
      equation. To assess the incremental prognostic value of eGFR(CKD-EPI), the net
      reclassification improvement was calculated for the composite end point of CV
      death, recurrent myocardial infarction, heart failure, or stroke. RESULTS: Twenty
      four percent of the subjects were reclassified into a different eGFR category
      using eGFR(CKD-EPI). The composite end point occurred in 33% of the subjects in
      this cohort. Based on eGFR(CKD-EPI), subjects reclassified into a higher eGFR
      experienced fewer events than those reclassified into a lower eGFR (21% vs 43%).
      In unadjusted analyses, the composite end point risk in subjects with eGFR
      between 75 and 90 mL/min per 1.73 m(2) was comparable with the referent group
      (eGFR between 90 and 105) using eGFR(MDRD) (hazard ratio 1.1, 95% CI 0.9-1.2) but
      was significantly higher using eGFR(CKD-EPI) (hazard ratio 1.2, 95% CI 1.1-1.4).
      The net reclassification improvement for eGFR(CKD-EPI) over eGFR(MDRD) was 8.7%.
      CONCLUSION: The CKD-EPI equation provides more accurate risk stratification than
      the MDRD Study equation in patients at high risk for CV disease, including
      identification of increased risk at mildly decreased eGFR.

PMID- 21884876
TI  - The CHADS2 score predicts ischemic stroke in the absence of atrial fibrillation
      among subjects with coronary heart disease: data from the Heart and Soul Study.
AB  - BACKGROUND: We sought to evaluate the prognostic performance of the CHADS(2)
      score for prediction of ischemic stroke/transient ischemic attack (TIA) in
      subjects with coronary heart disease (CHD) without atrial fibrillation (AF).
      METHODS: In 916 nonanticoagulated outpatients with stable CHD and no AF by
      baseline electrocardiogram, we calculated CHADS(2) scores (congestive heart
      failure, hypertension, age >=75 years, diabetes [1 point each], and prior stroke
      or TIA [2 points]). The primary outcome was time to ischemic stroke or TIA over a
      mean follow-up of 6.4 +/- 2.3 years. RESULTS: Over 5,821 person-years of follow
      up, 40 subjects had an ischemic stroke/TIA (rate 0.69/100 person-years, 95% CI
      0.50-0.94). Compared with subjects with low (0-1) CHADS(2) scores, those with
      intermediate (2-3) and high (4-6) CHADS(2) scores had an increased rate of
      stroke/TIA, even after adjustment for age, tobacco, antiplatelet therapy,
      statins, and angiotensin inhibitors (CHADS(2) score 2-3: HR 2.4, 95% CI 1.1-5.3,
      P = .03; CHADS(2) score 4-6: HR 4.0, 95% CI 1.5-10.6, P = .006). Model
      discrimination (c-statistic = 0.65) was comparable with CHADS(2) model fit in
      published AF-only cohorts. CONCLUSIONS: The CHADS(2) score predicts ischemic
      stroke/TIA in subjects with stable CHD and no baseline AF. The event rate in non
      AF subjects with high CHADS(2) scores (5-6) was comparable with published rates
      in AF patients with moderate CHADS(2) scores (1-2), a population known to derive
      benefit from stroke prevention therapies. These findings should inform efforts to
      determine whether stroke prevention therapies or screening for silent AF may
      benefit subjects with stable CHD and high CHADS(2) scores.

PMID- 21884877
TI  - Pulmonary arterial capacitance in children with idiopathic pulmonary arterial
      hypertension and pulmonary arterial hypertension associated with congenital heart
      disease: relation to pulmonary vascular resistance, exercise capacity, and
      survival.
AB  - BACKGROUND: Pediatric pulmonary arterial hypertension (PAH), whether idiopathic
      PAH (iPAH) or PAH associated with congenital heart disease (aPAH), carries high
      morbidity and mortality. Low pulmonary arterial capacitance (PAC), defined as
      right ventricular stroke volume/pulmonary artery pulse pressure, is a risk factor
      for mortality in adults with PAH. However, the relation of PAC to pulmonary
      vascular resistance (PVR), exercise endurance, and survival is poorly defined in
      children. METHODS: Catheterization and clinical data of children with PAH (mean
      pulmonary artery pressure >25 mm Hg) were reviewed. Children with pulmonary
      shunts, stents, collaterals, or pulmonary venous hypertension were excluded.
      Primary outcomes were 6-minute walk distance and freedom from death/lung
      transplant. RESULTS: Forty-seven patients were studied. Nineteen (43%) had iPAH,
      and 28 (57%) had aPAH (7.1 +/- 6.2 vs 8.4 +/- 5.5 years, P = .45). Patients with
      iPAH had higher PVR indexed for body surface area (PVRi), lower indexed PAC
      (PACi), lower exercise tolerance, and lower freedom from death/lung transplant
      than patients with aPAH. Both higher PVRi (P < .0001) and lower PACi (P = .02)
      were associated with shorter 6-minute walk distance. A PACi <0.70 mL/mm Hg per
      square meter or >1.25 mL/mm Hg per square meter and a PVRi >13 Wood units * m(2)
      were associated with decreased freedom from death or lung transplant. The
      relationships between PVRi and PACi and survival were independent of each other
      and not confounded by etiologic group. CONCLUSIONS: Low PACi and high PVRi are
      independently associated with low 6-minute walk distance and survival in children
      with PAH. Therefore, both should be assessed for better prognostication and
      management in this high-risk population.

PMID- 21884879
TI  - Piercing the impact factor and promoting the EigenfactorTM.

PMID- 21884880
TI  - Should we focus on hematocrit or hemoglobin in patients with eisenmenger
      syndrome?

PMID- 21884881
TI  - Initial downward deflection in lead aVR in cyclic antidepressant poisoning-S or Q
      Wave?

PMID- 21884882
TI  - Immortal person time bias in pharmacoepidemiological studies of antihypertensive
      drugs.

PMID- 21884883
TI  - Adherence to medications in revascularized patients.

PMID- 21884886
TI  - Mechanisms of host cell invasion by Trypanosoma cruzi.
AB  - One of the more accepted concepts in our understanding of the biology of early
      Trypanosoma cruzi-host cell interactions is that the mammalian-infective
      trypomastigote forms of the parasite must transit the host cell lysosomal
      compartment in order to establish a productive intracellular infection. The
      acidic environment of the lysosome provides the appropriate conditions for
      parasite-mediated disruption of the parasitophorous vacuole and release of T.
      cruzi into the host cell cytosol, where replication of intracellular amastigotes
      occurs. Recent findings indicate a level of redundancy in the lysosome-targeting
      process where T. cruzi trypomastigotes exploit different cellular pathways to
      access host cell lysosomes in non-professional phagocytic cells. In addition, the
      reversible nature of the host cell penetration process was recently demonstrated
      when conditions for fusion of the nascent parasite vacuole with the host
      endosomal-lysosomal system were not met. Thus, the concept of parasite retention
      as a critical component of the T. cruzi invasion process was introduced. Although
      it is clear that host cell recognition, attachment and signalling are required to
      initiate invasion, integration of this knowledge with our understanding of the
      different routes of parasite entry is largely lacking. In this chapter, we focus
      on current knowledge of the cellular pathways exploited by T. cruzi
      trypomastigotes to invade non-professional phagocytic cells and to gain access to
      the host cell lysosome compartment.

PMID- 21884885
TI  - Bioactive lipids in Trypanosoma cruzi infection.
AB  - Chagas disease is caused by Trypanosoma cruzi, a protozoan parasite. Chagas
      disease remains a serious health problem in large parts of Mexico and Central and
      South America, where it is a major cause of morbidity and mortality. This disease
      is being increasingly recognized in non-endemic regions due to immigration. Heart
      disease develops in 10-30% of infected individuals. It is increasingly clear that
      parasite- and host-derived bioactive lipids potently modulate disease
      progression. Many of the changes that occur during acute and chronic Chagas
      disease can be accounted for by the effects of arachidonic acid (AA)-derived
      lipids such as leukotrienes, lipoxins, H(P)ETEs, prostaglandins (PGs) and
      thromboxane. During the course of infection with T. cruzi, changes in circulating
      levels of AA metabolites are observed. Antagonism of PG synthesis with
      cyclooxygenase (COX) inhibitors has both beneficial and adverse effects.
      Treatment with COX inhibitors during acute infection may result in increased
      parasite load and mortality. However, treatment instituted during chronic
      infection may be beneficial with no increase in mortality and substantial
      improvement with cardiac function. Recently, T. cruzi infection of mice deficient
      in AA biosynthetic enzymes for various pathways has yielded more insightful data
      than pharmacological inhibition and has highlighted the potential deleterious
      effects of inhibitors due to "off-target" actions. Using COX-1 null mice, it was
      observed that parasite biosynthesis is dependent upon host metabolism, that the
      majority of TXA(2) liberated during T. cruzi infection is derived from the
      parasite and that this molecule may act as a quorum sensor to control parasite
      growth/differentiation. Thus, eicosanoids present during acute infection may act
      as immunomodulators aiding the transition to, and maintenance of, the chronic
      stage of the disease. It is also likely that the same mediators that initially
      function to ensure host survival may later contribute to cardiovascular damage.
      Collectively, the eicosanoids represent a new series of targets for therapy in
      Chagas disease with defined potential therapeutic windows in which to apply these
      agents for greatest effect. A deeper understanding of the mechanism of action of
      non-steroidal anti-inflammatory drugs may provide clues to the differences
      between host responses in acute and chronic T. cruzi infection.

PMID- 21884887
TI  - Gap junctions and chagas disease.
AB  - Gap junction channels provide intercellular communication between cells. In the
      heart, these channels coordinate impulse propagation along the conduction system
      and through the contractile musculature, thereby providing synchronous and
      optimal cardiac output. As in other arrhythmogenic cardiac diseases, chagasic
      cardiomyopathy is associated with decreased expression of the gap junction
      protein connexin43 (Cx43) and its gene. Our studies of cardiac myocytes infected
      with Trypanosoma cruzi have revealed that synchronous contraction is greatly
      impaired and gap junction immunoreactivity is lost in infected cells. Such
      changes are not seen for molecules forming tight junctions, another component of
      the intercalated disc in cardiac myocytes. Transcriptomic studies of hearts from
      mouse models of Chagas disease and from acutely infected cardiac myocytes in
      vitro indicate profound remodelling of gene expression patterns involving heart
      rhythm determinant genes, suggesting underlying mechanisms of the functional
      pathology. One curious feature of the altered expression of Cx43 and its gene
      expression is that it is limited in both extent and location, suggesting that the
      more global deterioration in cardiac function may result in part from spread of
      damage signals from more seriously compromised cells to healthier ones.

PMID- 21884889
TI  - Infection-associated vasculopathy in experimental chagas disease pathogenic roles
      of endothelin and kinin pathways.
AB  - Acting at the interface between microcirculation and immunity, Trypanosoma cruzi
      induces modifications in peripheral tissues which translate into mutual benefits
      to host/parasite balance. In this chapter, we will review evidence linking
      infection-associated vasculopathy to the proinflammatory activity of a small
      subset of T. cruzi molecules, namely GPI-linked mucins, cysteine proteases
      (cruzipain), surface glycoproteins of the trans-sialidase family and/or parasite
      derived eicosanoids (thromboxane A(2)). Initial insight into pathogenesis came
      from research in animal models showing that myocardial fibrosis is worsened as
      result of endothelin upregulation by infected cardiovascular cells. Paralleling
      these studies, the kinin system emerged as a proteolytic mechanism that links
      oedematogenic inflammation to immunity. Analyses of the dynamics of inflammation
      revealed that tissue culture trypomastigotes elicit interstitial oedema in
      peripheral sites of infection through synergistic activation of toll-like 2
      receptors (TLR2) and G-protein-coupled bradykinin receptors, respectively,
      engaged by tGPI (TLR2 ligand) and kinin peptides (bradykinin B2 receptors
      (BK(2)R) ligands) proteolytically generated by cruzipain. Further downstream,
      kinins stimulate lymph node dendritic cells via G-protein-coupled BK(2)R, thus
      converting these specialized antigen-presenting cells into T(H)1 inducers.
      Tightly regulated by angiotensin-converting enzyme, the intact kinins (BK(2)R
      agonists) may be processed by carboxypeptidase M/N, generating [des-Arg]-kinins,
      which activates BK(1)R, a subtype of GPCR that is upregulated by cardiovascular
      cells during inflammation. Ongoing studies may clarify if discrepancies between
      proinflammatory phenotypes of T. cruzi strains may be ascribed, at least in part,
      to variable expression of TLR2 ligands and cruzipain isoforms.

PMID- 21884888
TI  - The vasculature in chagas disease.
AB  - The cardiovascular manifestations of Chagas disease are well known. However, the
      contribution of the vasculature and specifically the microvasculature has
      received little attention. This chapter reviews the evidence supporting the
      notion that alterations in the microvasculature especially in the heart
      contribute to the pathogenesis of chagasic cardiomyopathy. These data may also be
      important in understanding the contributions of the microvasculature in the
      aetiologies of other cardiomyopathies. The role of endothelin-1 and of
      thromboxane A(2) vascular spasm and platelet aggregation is also discussed.
      Further, these observations may provide target(s) for intervention.

PMID- 21884890
TI  - Autoimmunity.
AB  - The scarcity of Trypanosoma cruzi in inflammatory lesions of chronic Chagas
      disease led early investigators to suggest that tissue damage had an autoimmune
      nature. In spite of parasite persistence in chronic Chagas disease, several
      reports indicate that inflammatory tissue damage may not be correlated to the
      local presence of T. cruzi. A significant number of reports have described
      autoantibodies and self-reactive T cells, often cross-reactive with T. cruzi
      antigens, both in patients and in animal models. Evidence for a direct
      pathogenetic role of autoimmunity was suggested by the development of lesions
      after immunization with T. cruzi antigens or passive transfer of lymphocytes from
      infected animals, and the amelioration of chronic myocarditis in animals made
      tolerant to myocardial antigens. Autoimmune and T. cruzi-specific innate or
      adaptative responses are not incompatible or mutually exclusive, and it is likely
      that a combination of both is involved in the pathogenesis of chronic Chagas
      disease cardiomyopathy. The association between persistent infection and
      autoimmune diseases-such as multiple sclerosis or diabetes mellitus-suggests that
      post-infectious autoimmunity may be a frequent finding. Here, we critically
      review evidence for autoimmune phenomena and their possible pathogenetic role in
      human Chagas disease and animal models, with a focus on chronic Chagas disease
      cardiomyopathy.

PMID- 21884891
TI  - ROS signalling of inflammatory cytokines during Trypanosoma cruzi infection.
AB  - Inflammation is a host defence activated by exogenous (e.g. pathogen-derived,
      pollutants) or endogenous (e.g. reactive oxygen species-ROS) danger signals.
      Mostly, endogenous molecules (or their derivatives) have well-defined
      intracellular function but become danger signal when released or exposed
      following stress or injury. In this review, we discuss the potential role of ROS
      in chronic evolution of inflammatory cardiovascular diseases, using our
      experiences working on chagasic cardiomyopathy as a focus-point.

PMID- 21884892
TI  - Inflammation and Chagas disease some mechanisms and relevance.
AB  - Chagas cardiomyopathy is caused by infection with flagellated protozoan
      Trypanosoma cruzi. In patients, there is a fine balance between control of the
      replication and the intensity of the inflammatory response so that the host is
      unable to eliminate the parasite resulting in the parasite persisting as a
      lifelong infection in most individuals. However, the parasite persists in such a
      way that it causes no or little disease. This chapter reviews our understanding
      of many of the mediators of inflammation and cells which are involved in the
      inflammatory response of mammals to T. cruzi infection. Particular emphasis is
      given to the role of chemokines, endothelin and lipid mediators. Understanding
      the full range of mediators and cells present and how they interact with each
      other in Chagas disease may shed light on how we modulate disease pathogenesis
      and define new approaches to treat or prevent the disease.

PMID- 21884893
TI  - Neurodegeneration and neuroregeneration in Chagas disease.
AB  - Autonomic dysfunction plays a significant role in the development of chronic
      Chagas disease (CD). Destruction of cardiac parasympathetic ganglia can underlie
      arrhythmia and heart failure, while lesions of enteric neurons in the intestinal
      plexuses are a direct cause of aperistalsis and megasyndromes. Neuropathology is
      generated by acute infection when the parasite, though not directly damaging to
      neuronal cells, elicits immune reactions that can become cytotoxic, inducing
      oxidative stress and neurodegeneration. Anti-neuronal autoimmunity may further
      contribute to neuropathology. Much less clear is the mechanism of subsequent
      neuronal regeneration in patients that survive acute infection. Morphological and
      functional recovery of the peripheral neurons in these patients correlates with
      the absence of CD clinical symptoms, while persistent neuronal deficiency is
      observed for the symptomatic group. The discovery that Trypanosoma cruzi trans
      sialidase can moonlight as a parasite-derived neurotrophic factor (PDNF) suggests
      that the parasite might influence the balance between neuronal degeneration and
      regeneration. PDNF functionally mimics mammalian neurotrophic factors in that it
      binds and activates neurotrophin Trk tyrosine kinase receptors, a mechanism which
      prevents neurodegeneration. PDNF binding to Trk receptors triggers PI3K/Akt/GSK
      3beta and MAPK/Erk/CREB signalling cascades which in neurons translates into
      resistance to oxidative and nutritional stress, and inhibition of apoptosis,
      whereas in the cytoplasm of infected cells, PDNF represents a substrate-activator
      of the host Akt kinase, enhancing host-cell survival until completion of the
      intracellular cycle of the parasite. Such dual activity of PDNF provides
      sustained activation of survival mechanisms which, while prolonging parasite
      persistence in host tissues, can underlie distinct outcomes of CD.

PMID- 21884895
TI  - Editorial comment.

PMID- 21884897
TI  - Fertility concerns for the aging male.
AB  - Because of many societal factors, the number of men over the age of 35 desiring
      to conceive children has increased over the past 40 years. The purpose of this
      review is to identify the mechanisms of aging on male fertility, to evaluate the
      genetic risk for the offspring, and to provide counseling for the older male.
      Most evidence suggests trends that increased paternal age has negative effects on
      fertility and some genetic risk for offspring, but the age at which the risk
      develops and the magnitude of risk are poorly defined.

PMID- 21884894
TI  - Adipose tissue, diabetes and Chagas disease.
AB  - Adipose tissue is the largest endocrine organ in the body and is composed
      primarily of adipocytes (fat cells) but also contains fibroblasts, endothelial
      cells, smooth muscle cells, macrophages and lymphocytes. Adipose tissue and the
      adipocyte are important in the regulation of energy metabolism and of the immune
      response. Adipocytes also synthesize adipokines such as adiponectin which is
      important in the regulation of insulin sensitivity and inflammation. Infection of
      mice with Trypanosoma cruzi results in an upregulation of inflammation in adipose
      tissue that begins during the acute phase of infection and persists into the
      chronic phase. The adipocyte is both a target of infection and a reservoir for
      the parasite during the chronic phase from which recrudescence of the infection
      may occur during periods of immunosuppression.

PMID- 21884898
TI  - Editorial comment.

PMID- 21884900
TI  - Editorial comment.

PMID- 21884902
TI  - Editorial comment.

PMID- 21884904
TI  - Editorial comment.

PMID- 21884906
TI  - Editorial comment.

PMID- 21884908
TI  - Editorial comment.

PMID- 21884909
TI  - Editorial comment.

PMID- 21884912
TI  - Editorial comment.

PMID- 21884913
TI  - Editorial comment.

PMID- 21884914
TI  - Editorial comment.

PMID- 21884917
TI  - Editorial comment.

PMID- 21884918
TI  - Editorial comment.

PMID- 21884920
TI  - Editorial comment.

PMID- 21884923
TI  - Re: Eggert-Kruse et al.: Are chlamydial lipopolysaccharide-directed antibodies in
      seminal plasma or serum clinically significant during investigation of male
      infertility? (Urology 2011;77:1101-1106).

PMID- 21884924
TI  - Re: Miocinovic et al.: Avoiding androgen deprivation therapy in men with high
      risk prostate cancer: the role of radical prostatectomy as initial treatment.
      (Urology 2011;77:946-950).

PMID- 21884926
TI  - A new FOXO pathway required for leukemogenesis.
AB  - In cancer, the FOXO family of transcription factors functions as tumor
      suppressors and is directly inactivated by oncogenic signaling through the
      PI3K/AKT pathway. Now, Skykes et al. (2011) identify a paradoxical requirement
      for FOXOs in the maintenance of leukemia-initiating cells.

PMID- 21884927
TI  - Signaling through chromatin: setting the scene at kinetochores.
AB  - Histone H3 lysine 4 trimethylation needed for transcription is mediated by the
      Set1 methyltransferase and requires prior monoubiquitination of histone H2B. In
      this issue, Latham et al. (2011) report that dimethylation of the yeast
      kinetochore protein Dam1 by Set1 similarly requires H2B monoubiquitination. Thus,
      H2B ubiquitination signals for methylation beyond chromatin.

PMID- 21884928
TI  - When T cells run out of breath: the HIF-1alpha story.
AB  - In this issue, Dang et al. (2011) report a role for the hypoxia-induced
      transcription factor HIF-1alpha in regulating the differentiation of T cell
      subsets that impact both inflammation and its resolution. Their findings
      illustrate how metabolic signals can alter the balance between inflammation and
      tolerance and present a potential therapeutic opportunity for the treatment of
      diseases associated with chronic inflammation.

PMID- 21884929
TI  - Basal synaptic transmission: astrocytes rule!
AB  - In this issue, Panatier et al. (2011) show that astrocytes detect synaptic
      activity induced by single action potentials and upregulate basal synaptic
      transmission through calcium-dependent mechanisms and purinergic signaling. These
      results demonstrate the relevance of astrocyte calcium in neurophysiology and
      confirm that astrocytes are actively involved in synaptic function.

PMID- 21884930
TI  - Niche crosstalk: intercellular signals at the hair follicle.
AB  - A recent series of papers, including Festa et al. (2011) in this issue, has
      revealed unexpected interdependent relationships among cell populations residing
      in and around the hair follicle. These interactions between different lineages of
      stem cells are crucial for hair follicle growth and cycling and point to a
      complex crosstalk in stem cell niches.

PMID- 21884931
TI  - Autophagy and aging.
AB  - Genetic inhibition of autophagy induces degenerative changes in mammalian tissues
      that resemble those associated with aging, and normal and pathological aging are
      often associated with a reduced autophagic potential. Pharmacological or genetic
      manipulations that increase life span in model organisms often stimulate
      autophagy, and its inhibition compromises the longevity-promoting effects of
      caloric restriction, Sirtuin 1 activation, inhibition of insulin/insulin growth
      factor signaling, or the administration of rapamycin, resveratrol, or spermidine.
      Here, we discuss the probable cause and effect relationship between perturbed
      autophagy and aging, as well as possible molecular mechanisms that may mediate
      the anti-aging effects of autophagy.

PMID- 21884932
TI  - AKT/FOXO signaling enforces reversible differentiation blockade in myeloid
      leukemias.
AB  - AKT activation is associated with many malignancies, where AKT acts, in part, by
      inhibiting FOXO tumor suppressors. We show a converse role for AKT/FOXOs in acute
      myeloid leukemia (AML). Rather than decreased FOXO activity, we observed that
      FOXOs are active in ~40% of AML patient samples regardless of genetic subtype. We
      also observe this activity in human MLL-AF9 leukemia allele-induced AML in mice,
      where either activation of Akt or compound deletion of FoxO1/3/4 reduced leukemic
      cell growth, with the latter markedly diminishing leukemia-initiating cell (LIC)
      function in vivo and improving animal survival. FOXO inhibition resulted in
      myeloid maturation and subsequent AML cell death. FOXO activation inversely
      correlated with JNK/c-JUN signaling, and leukemic cells resistant to FOXO
      inhibition responded to JNK inhibition. These data reveal a molecular role for
      AKT/FOXO and JNK/c-JUN in maintaining a differentiation blockade that can be
      targeted to inhibit leukemias with a range of genetic lesions.

PMID- 21884933
TI  - Chromatin signaling to kinetochores: transregulation of Dam1 methylation by
      histone H2B ubiquitination.
AB  - Histone H3K4 trimethylation by the Set1/MLL family of proteins provides a
      hallmark for transcriptional activity from yeast to humans. In S. cerevisiae,
      H3K4 methylation is mediated by the Set1-containing COMPASS complex and is
      regulated in trans by prior ubiquitination of histone H2BK123. All of the events
      that regulate H2BK123ub and H3K4me are thought to occur at gene promoters. Here
      we report that this pathway is indispensable for methylation of the only other
      known substrate of Set1, K233 in Dam1, at kinetochores. Deletion of RAD6, BRE1,
      or Paf1 complex members abolishes Dam1 methylation, as does mutation of H2BK123.
      Our results demonstrate that Set1-mediated methylation is regulated by a general
      pathway regardless of substrate that is composed of transcriptional regulatory
      factors functioning independently of transcription. Moreover, our data identify a
      node of regulatory crosstalk in trans between a histone modification and
      modification on a nonhistone protein, demonstrating that changing chromatin
      states can signal functional changes in other essential cellular proteins and
      machineries.

PMID- 21884934
TI  - Control of embryonic stem cell lineage commitment by core promoter factor, TAF3.
AB  - Deciphering the molecular basis of pluripotency is fundamental to our
      understanding of development and embryonic stem cell function. Here, we report
      that TAF3, a TBP-associated core promoter factor, is highly enriched in ES cells.
      In this context, TAF3 is required for endoderm lineage differentiation and
      prevents premature specification of neuroectoderm and mesoderm. In addition to
      its role in the core promoter recognition complex TFIID, genome-wide binding
      studies reveal that TAF3 localizes to a subset of chromosomal regions bound by
      CTCF/cohesin that are selectively associated with genes upregulated by TAF3.
      Notably, CTCF directly recruits TAF3 to promoter distal sites and TAF3-dependent
      DNA looping is observed between the promoter distal sites and core promoters
      occupied by TAF3/CTCF/cohesin. Together, our findings support a new role of TAF3
      in mediating long-range chromatin regulatory interactions that safeguard the
      finely-balanced transcriptional programs underlying pluripotency.

PMID- 21884935
TI  - A mechanism for tunable autoinhibition in the structure of a human
      Ca2+/calmodulin- dependent kinase II holoenzyme.
AB  - Calcium/calmodulin-dependent kinase II (CaMKII) forms a highly conserved
      dodecameric assembly that is sensitive to the frequency of calcium pulse trains.
      Neither the structure of the dodecameric assembly nor how it regulates CaMKII are
      known. We present the crystal structure of an autoinhibited full-length human
      CaMKII holoenzyme, revealing an unexpected compact arrangement of kinase domains
      docked against a central hub, with the calmodulin-binding sites completely
      inaccessible. We show that this compact docking is important for the
      autoinhibition of the kinase domains and for setting the calcium response of the
      holoenzyme. Comparison of CaMKII isoforms, which differ in the length of the
      linker between the kinase domain and the hub, demonstrates that these
      interactions can be strengthened or weakened by changes in linker length. This
      equilibrium between autoinhibited states provides a simple mechanism for tuning
      the calcium response without changes in either the hub or the kinase domains.

PMID- 21884936
TI  - Rescue of DeltaF508-CFTR trafficking via a GRASP-dependent unconventional
      secretion pathway.
AB  - The most prevalent disease-causing mutation of CFTR is the deletion of Phe508
      (DeltaF508), which leads to defects in conventional Golgi-mediated exocytosis and
      cell surface expression. We report that DeltaF508-CFTR surface expression can be
      rescued in vitro and in vivo by directing it to an unconventional GRASP-dependent
      secretion pathway. An integrated molecular and physiological analysis indicates
      that mechanisms associated with ER stress induce cell surface trafficking of the
      ER core-glycosylated wild-type and DeltaF508-CFTR via the GRASP-dependent
      pathway. Phosphorylation of a specific site of GRASP and the PDZ-based
      interaction between GRASP and CFTR are critical for this unconventional surface
      trafficking. Remarkably, transgenic expression of GRASP in DeltaF508-CFTR mice
      restores CFTR function and rescues mouse survival without apparent toxicity.
      These findings provide insight into how unconventional protein secretion is
      activated, and offer a potential therapeutic strategy for the treatment of cystic
      fibrosis and perhaps diseases stemming from other misfolded proteins.

PMID- 21884937
TI  - Adipocyte lineage cells contribute to the skin stem cell niche to drive hair
      cycling.
AB  - In mammalian skin, multiple types of resident cells are required to create a
      functional tissue and support tissue homeostasis and regeneration. The cells that
      compose the epithelial stem cell niche for skin homeostasis and regeneration are
      not well defined. Here, we identify adipose precursor cells within the skin and
      demonstrate that their dynamic regeneration parallels the activation of skin stem
      cells. Functional analysis of adipocyte lineage cells in mice with defects in
      adipogenesis and in transplantation experiments revealed that intradermal
      adipocyte lineage cells are necessary and sufficient to drive follicular stem
      cell activation. Furthermore, we implicate PDGF expression by immature adipocyte
      cells in the regulation of follicular stem cell activity. These data highlight
      adipogenic cells as skin niche cells that positively regulate skin stem cell
      activity, and suggest that adipocyte lineage cells may alter epithelial stem cell
      function clinically.

PMID- 21884939
TI  - Photoconversion and nuclear trafficking cycles determine phytochrome A's response
      profile to far-red light.
AB  - Phytochrome A (phyA) is the only photoreceptor in plants, initiating responses in
      far-red light and, as such, essential for survival in canopy shade. Although the
      absorption and the ratio of active versus total phyA are maximal in red light,
      far-red light is the most efficient trigger of phyA-dependent responses. Using a
      joint experimental-theoretical approach, we unravel the mechanism underlying this
      shift of the phyA action peak from red to far-red light and show that it relies
      on specific molecular interactions rather than on intrinsic changes to phyA's
      spectral properties. According to our model, the dissociation rate of the phyA
      FHY1/FHL nuclear import complex is a principle determinant of the phyA action
      peak. The findings suggest how higher plants acquired the ability to sense far
      red light from an ancestral photoreceptor tuned to respond to red light.

PMID- 21884938
TI  - Peptidoglycan remodeling and conversion of an inner membrane into an outer
      membrane during sporulation.
AB  - Two hallmarks of the Firmicute phylum, which includes the Bacilli and Clostridia
      classes, are their ability to form endospores and their "Gram-positive" single
      membraned, thick-cell-wall envelope structure. Acetonema longum is part of a
      lesser-known family (the Veillonellaceae) of Clostridia that form endospores but
      that are surprisingly "Gram negative," possessing both an inner and outer
      membrane and a thin cell wall. Here, we present macromolecular resolution, 3D
      electron cryotomographic images of vegetative, sporulating, and germinating A.
      longum cells showing that during the sporulation process, the inner membrane of
      the mother cell is inverted and transformed to become the outer membrane of the
      germinating cell. Peptidoglycan persists throughout, leading to a revised,
      "continuous" model of its role in the process. Coupled with genomic analyses,
      these results point to sporulation as a mechanism by which the bacterial outer
      membrane may have arisen and A. longum as a potential "missing link" between
      single- and double-membraned bacteria.

PMID- 21884941
TI  - SnapShot: Histone readers.

PMID- 21884942
TI  - Radiation-induced heart morbidity after adjuvant radiotherapy of early breast
      cancer - Is it still an issue?

PMID- 21884940
TI  - Global proteomic assessment of the classical protein-tyrosine phosphatome and
      "Redoxome".
AB  - Protein-tyrosine phosphatases (PTPs), along with protein-tyrosine kinases, play
      key roles in cellular signaling. All Class I PTPs contain an essential active
      site cysteinyl residue, which executes a nucleophilic attack on substrate
      phosphotyrosyl residues. The high reactivity of the catalytic cysteine also
      predisposes PTPs to oxidation by reactive oxygen species, such as H(2)O(2).
      Reversible PTP oxidation is emerging as an important cellular regulatory
      mechanism and might contribute to diseases such as cancer. We exploited these
      unique features of PTP enzymology to develop proteomic methods, broadly
      applicable to cell and tissue samples, that enable the comprehensive
      identification and quantification of expressed classical PTPs (PTPome) and the
      oxidized subset of the PTPome (oxPTPome). We find that mouse and human cells and
      tissues, including cancer cells, display distinctive PTPomes and oxPTPomes,
      revealing additional levels of complexity in the regulation of protein-tyrosine
      phosphorylation in normal and malignant cells.

PMID- 21884943
TI  - Percutaneous edge-to-edge mitral valve repair: assessment of immediate post
      procedural treatment effect using color 3-dimensional transesophageal
      echocardiography and cardiac magnetic resonance imaging.

PMID- 21884944
TI  - 10 years of intracoronary and intramyocardial bone marrow stem cell therapy of
      the heart: from the methodological origin to clinical practice.
AB  - Intracoronary and intramyocardial stem cell therapy aim at the repair of
      compromised myocardium thereby--as a causal treatment--preventing ventricular
      remodeling and improving overall performance. Since the first-in-human use of
      bone marrow stem cells (BMCs) after acute myocardial infarction in 2001, a large
      number of clinical studies have demonstrated their clinical benefit: BMC therapy
      can be performed with usual cardiac catheterization techniques in the conscious
      patient as well as also easily during cardiosurgical interventions. New York
      Heart Association severity degree of patients as well as physical activity
      improve in addition to ("on top" of) all other therapeutic regimens. Stem cell
      therapy also represents an ultimate approach in advanced cardiac failure. For
      acute myocardial infarction and chronic ischemia, long-term mortality after 1 and
      5 years, respectively, is significantly reduced. A few studies also indicate
      beneficial effects for chronic dilated cardiomyopathy. The clinical use of
      autologous BMC therapy implies no ethical problems, when unmodified primary cells
      are used. With the use of primary BMCs, there are no major stem cell-related side
      effects, especially no cardiac arrhythmias and inflammation. Various mechanisms
      of the stem cell action in the human heart are discussed, for example, cell
      transdifferentiation, cell fusion, activation of intrinsic cardiac stem cells,
      and cytokine-mediated effects. New techniques allow point-of-care cell
      preparations, for example, within the cardiac intervention or operation theater,
      thereby providing short preparation time, facilitated logistics of cell
      transport, and reasonable cost effectiveness of the whole procedure. The 3 main
      indications are acute infarction, chronic ischemic heart failure, and dilated
      cardiomyopathy. Future studies are desirable to further elucidate the mechanisms
      of stem cell action and to extend the current use of intracoronary and/or
      intramyocardial stem cell therapy by larger and presumably multicenter and
      randomized trials.

PMID- 21884945
TI  - First experience with drug-eluting balloons in infrapopliteal arteries:
      restenosis rate and clinical outcome.
AB  - OBJECTIVES: The purpose of this study was to investigate the efficacy of drug
      eluting balloons (DEBs) in the treatment of long infrapopliteal lesions with
      regard to the short-term restenosis rate and midterm clinical result. BACKGROUND:
      Restenosis rates of long-segment tibial artery disease are very high. Recently, a
      restenosis rate of 69% at 3 months after standard balloon angioplasty was
      demonstrated. METHODS: Infrapopliteal angioplasty was performed with a paclitaxel
      eluting balloon (In.Pact Amphirion, Medtronic, Minneapolis, Minnesota). Clinical
      and angiographic follow-up was performed at 3 months to detect binary restenosis,
      and further clinical assessment was performed over a 12-month period thereafter.
      RESULTS: In 104 patients, 109 limbs were treated for critical limb ischemia
      (82.6%) or severe claudication (17.4%). Mean lesion length of the arteries
      treated was 176 +/- 88 mm. Angiography studied in 84 treated arteries at 3 months
      showed a restenosis in 27.4% (19.1% had restenosis of more than 50%, and 8.3%
      were totally occluded) and usually occurred focally. Only in 9.5% of all
      angiographically followed up arteries was the entire treated segment restenosed
      or reoccluded. During a follow-up period of 378 +/- 65 days, 1 patient was lost
      and 17 died. Of the 91 limbs remaining in the analysis, clinical improvement was
      present in 83 (91.2%). Complete wound healing occurred in 74.2%, whereas major
      amputation occurred in 4 patients, resulting in limb salvage of 95.6% for
      patients with critical limb ischemia. CONCLUSIONS: The early restenosis rate of
      long-segment infrapopliteal disease is significantly lower after treatment with
      DEBs compared with historical data using uncoated balloons. Randomized trials are
      required to show whether this difference will lead to improvement in clinical
      outcomes.

PMID- 21884946
TI  - The breakthrough balloon for critical limb ischemia?

PMID- 21884947
TI  - Clinical and demographic predictors of outcomes in recent onset dilated
      cardiomyopathy: results of the IMAC (Intervention in Myocarditis and Acute
      Cardiomyopathy)-2 study.
AB  - OBJECTIVES: We sought to determine clinical and demographic predictors of
      recovery of left ventricular function for subjects with recent onset
      cardiomyopathy (ROCM). BACKGROUND: Although ROCM is a frequent reason for
      consultation and transplantation referral, its prognosis and natural history on
      contemporary therapy are unknown. METHODS: In the multicenter IMAC (Intervention
      in Myocarditis and Acute Cardiomyopathy)-2 study, subjects with a left
      ventricular ejection fraction (LVEF) of <=0.40, fewer than 6 months of symptom
      duration, and an evaluation consistent with idiopathic dilated cardiomyopathy or
      myocarditis were enrolled. LVEF was reassessed at 6 months, and subjects were
      followed up for 4 years. LVEF and event-free survival were compared by race, sex,
      and clinical phenotype. RESULTS: The cohort of 373 persons was 38% female and 21%
      black, with a mean age of 45 +/- 14 years. At entry, 91% were receiving
      angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and 82%
      were receiving beta-blockers, which increased to 92% and 94% at 6 months. LVEF
      was 0.24 +/- 0.08 at entry and 0.40 +/- 0.12 at 6 months (mean increase: 17 +/-
      13 ejection fraction units). Transplant-free survival at 1, 2, and 4 years was
      94%, 92%, and 88%, respectively; survival free of heart failure hospitalization
      was 88%, 82%, and 78%, respectively. In analyses adjusted for sex, baseline LVEF,
      and blood pressure, LVEF at 6 months was significantly lower in blacks than in
      nonblacks (p = 0.02). Left ventricular end-diastolic diameter at presentation was
      the strongest predictor of LVEF at 6 months (p < 0.0001). CONCLUSIONS: Outcomes
      in ROCM are favorable but differ by race. Left ventricular end-diastolic diameter
      by transthoracic echo at presentation was most predictive of subsequent
      myocardial recovery. (Genetic Modulation of Left Ventricular Recovery in Recent
      Onset Cardiomyopathy; NCT00575211).

PMID- 21884948
TI  - Lipolytic effects of B-type natriuretic peptide 1-32 in adipose tissue of heart
      failure patients compared with healthy controls.
AB  - OBJECTIVES: Our goal was to examine the role of B-type natriuretic peptide (BNP)
      in lipolysis regulation in heart failure (HF) patients. BACKGROUND: Enhanced
      adipose tissue lipolysis can contribute to myocardial lipid overload, insulin
      resistance, and cachexia in advanced HF. Natriuretic peptides were recently
      recognized to stimulate lipolysis in healthy subjects. METHODS: Ten nondiabetic
      HF patients (New York Heart Association functional class III, 50% nonischemic
      etiology) and 13 healthy subjects (control subjects) of similar age, sex, and
      body composition underwent a microdialysis study of subcutaneous abdominal
      adipose tissue. Four microdialysis probes were simultaneously perfused with 0.1
      MUM BNP(1-32,) 10 MUM BNP(1-32), 10 MUM norepinephrine (NE) or Ringer's solution.
      Outgoing dialysate glycerol concentration (DGC) was measured as an index of
      lipolysis. RESULTS: Spontaneous lipolysis was higher in HF patients compared with
      control subjects (DGC: 189 +/- 37 MUmol/l vs. 152 +/- 35 MUmol/l, p < 0.01).
      Response to NE was similar (p = 0.35) in HF patients and control subjects (DGC
      increase of 1.7 +/- 0.2-fold vs. 1.7 +/- 0.4-fold). BNP(1-32) 10 MUM markedly
      increased lipolysis in both HF patients and control subjects (DGC increase of 2.8
      +/- 0.5-fold vs. 3.2 +/- 0.3-fold), whereas the response to 0.1 MUM BNP(1-32) was
      more pronounced in HF patients (p = 0.02). In HF patients, spontaneous lipolysis
      positively correlated with insulin resistance and the response to BNP(1-32)
      negatively correlated with adiposity. CONCLUSIONS: BNP(1-32) exerts strong
      lipolytic effects in humans. Despite marked elevation of plasma immunoreactive
      BNP, the responsiveness of adipose tissue to BNP(1-32) is not attenuated in HF,
      possibly reflecting a deficiency of endogenous bioactive BNP. Lipolytic effects
      of BNP can contribute to excessive fatty acid mobilization in advanced HF.

PMID- 21884949
TI  - Metabolic crosstalk in heart failure new roles for B-type natriuretic peptide.

PMID- 21884950
TI  - Invasive acute hemodynamic response to guide left ventricular lead implantation
      predicts chronic remodeling in patients undergoing cardiac resynchronization
      therapy.
AB  - OBJECTIVES: We evaluated the relationship between acute hemodynamic response
      (AHR) and reverse remodeling (RR) in cardiac resynchronization therapy (CRT).
      BACKGROUND: CRT reduces mortality and morbidity in heart failure patients;
      however, up to 30% of patients do not derive symptomatic benefit. Higher
      proportions do not remodel. Multicenter trials have shown echocardiographic
      techniques are poor at improving response rates. We hypothesized the degree of
      AHR at implant can predict which patients remodel. METHODS: Thirty-three patients
      undergoing CRT (21 dilated and 12 ischemic cardiomyopathy) were studied. Left
      ventricular (LV) volumes were assessed before and after CRT. The AHR (maximum
      rate of left ventricular pressure [LV-dP/dt(max)]) was assessed at implant with a
      pressure wire in the LV cavity. Largest percentage rise in LV-dP/dt(max) from
      baseline (atrial antibradycardia pacing or right ventricular pacing with atrial
      fibrillation) to dual-chamber pacing (DDD)-LV was used to determine optimal
      coronary sinus LV lead position. Reverse remodeling was defined as reduction in
      LV end systolic volume >=15% at 6 months. RESULTS: The LV-dP/dt(max) increased
      significantly from baseline (801 +/- 194 mm Hg/s to 924 +/- 203 mm Hg/s, p <
      0.001) with DDD-LV pacing for the optimal LV lead position. The LV end systolic
      volume decreased from 186 +/- 68 ml to 157 +/- 68 ml (p < 0.001). Eighteen (56%)
      patients exhibited RR. There was a significant relationship between percentage
      rise in LV-dP/dt(max) and RR for DDD-LV pacing (p < 0.001). A similar
      relationship for AHR and RR in dilated cardiomyopathy and ischemic cardiomyopathy
      (p = 0.01 and p = 0.006) was seen. CONCLUSIONS: Acute hemodynamic response to LV
      pacing is useful for predicting which patients are likely to remodel in response
      to CRT both for dilated cardiomyopathy and ischemic cardiomyopathy. Using AHR has
      the potential to guide LV lead positioning and improve response rates.

PMID- 21884951
TI  - Guiding left ventricular lead positioning and refining ability to predict
      response and nonresponse to cardiac resynchronization therapy using dP/dt max:
      killing 3 birds with 1 high-fidelity wire?

PMID- 21884952
TI  - Strain-encoded cardiac magnetic resonance during high-dose dobutamine stress
      testing for the estimation of cardiac outcomes: comparison to clinical parameters
      and conventional wall motion readings.
AB  - OBJECTIVES: The purpose of this study was to determine the prognostic value of
      strain-encoded magnetic resonance imaging (SENC) during high-dose dobutamine
      stress cardiac magnetic resonance imaging (DS-MRI) compared with conventional
      wall motion readings. BACKGROUND: Detection of inducible ischemia by DS-MRI on
      the basis of assessing cine images is subjective and depends on the experience of
      the readers, which may influence not only the diagnostic classification but also
      the risk stratification of patients with ischemic heart disease. METHODS: In all,
      320 consecutive patients with suspected or known coronary artery disease
      underwent DS-MRI, using a standard protocol in a 1.5T MR scanner. Wall motion
      abnormalities (WMA) and myocardial strain were assessed at baseline and during
      stress, and outcome data including cardiac deaths, nonfatal myocardial
      infarctions ("hard events"), and revascularization procedures performed >90 days
      after the MR scans were collected. RESULTS: Thirty-five hard events occurred
      during a 28 +/- 9 month follow-up period, including 10 cardiac deaths and 25
      nonfatal myocardial infarctions, and 32 patients underwent coronary
      revascularization. Using a series of Cox proportional-hazards models, both
      resting and inducible WMA offered incremental information for the assessment of
      hard cardiac events compared to clinical variables (chi-square = 13.0 for
      clinical vs. chi-square = 26.1 by adding resting WMA, p < 0.001, vs. chi-square =
      39.3 by adding inducible WMA, p < 0.001). Adding visual SENC or quantitative
      strain rate reserve to this model further improved the prediction of outcome (chi
      square = 50.7 vs. chi-square = 52.5, p < 0.001 for both). In a subset of patients
      (n = 175) who underwent coronary angiography, SENC yielded significantly higher
      sensitivity for coronary artery disease detection (96% vs. 84%, p < 0.02),
      whereas specificity and accuracy were not significantly different (88% vs. 94%
      and 93% vs. 88%, p = NS for both). CONCLUSIONS: Strain-encoded MRI aids the
      accurate identification of patients at high risk for future cardiac events and
      revascularization procedures, beyond the assessment of conventional atherogenic
      risk factors and resting or inducible WMA on cine images. (Strain-Encoded Cardiac
      Magnetic Resonance Imaging as an Adjunct for Dobutamine Stress Testing;
      NCT00758654).

PMID- 21884953
TI  - Straining for perfection.

PMID- 21884954
TI  - Effects of beta-adrenergic antagonists in patients with chronic kidney disease: a
      systematic review and meta-analysis.
AB  - OBJECTIVES: The aim of this systematic review was to study the benefits and risks
      of beta-adrenergic antagonists (beta-blockers) in patients with chronic kidney
      disease (CKD). BACKGROUND: There is an excess burden of cardiovascular disease
      and death in people with CKD. Despite their potential benefits, the effects of
      beta-blockers in this population are uncertain. METHODS: CENTRAL (Cochrane
      Central Register of Controlled Trials), Medline (Medical Literature Analysis and
      Retrieval System Online), and Embase (Excerpta Medical Database) were searched
      for randomized controlled trials with at least 3 months of follow-up in patients
      with CKD stages 3 to 5 that reported mortality outcomes. Summary estimates of
      effect were obtained using a random effects model. RESULTS: Eight trials met
      criteria for review: 6 placebo-controlled trials involving 5,972 participants
      with chronic systolic heart failure and 2 angiotensin-converting enzyme inhibitor
      comparator trials involving 977 participants not known to have heart failure. In
      CKD patients with heart failure, compared with placebo, beta-blocker treatment
      reduced the risk of all-cause (risk ratio [RR]: 0.72, 95% confidence interval
      [CI]: 0.64 to 0.80) and cardiovascular mortality (RR: 0.66, 95% CI: 0.49 to
      0.89), but increased the risk of bradycardia (RR: 4.92, 95% CI: 3.20 to 7.55) and
      hypotension (RR: 5.08, 95% CI: 3.48 to 7.41). Quantitative meta-analysis was not
      performed for the non-heart failure studies due to substantial clinical diversity
      or lack of informative data. CONCLUSIONS: Treatment with beta-blockers improved
      all-cause mortality in patients with CKD and chronic systolic heart failure.
      There is insufficient evidence to conclude whether people with CKD who are not
      known to have heart failure derive benefit from beta-blockers.

PMID- 21884955
TI  - Chronic kidney disease and cardiovascular therapeutics: time to close the
      evidence gaps.

PMID- 21884956
TI  - Decreasing sleep-time blood pressure determined by ambulatory monitoring reduces
      cardiovascular risk.
AB  - OBJECTIVES: We investigated whether reduced cardiovascular risk is more related
      to the progressive decrease of asleep or awake blood pressure. BACKGROUND:
      Independent studies have concluded that elevated sleep-time blood pressure is a
      better predictor of cardiovascular risk than awake or 24-h blood pressure means.
      However, the impact on cardiovascular risk of changes in these ambulatory blood
      pressure characteristics has not been properly investigated. METHODS: We
      prospectively studied 3,344 subjects (1,718 men and 1,626 women), 52.6 +/- 14.5
      years of age, during a median follow-up of 5.6 years. Those with hypertension at
      baseline were randomized to ingest all their prescribed hypertension medications
      upon awakening or >=1 of them at bedtime. Blood pressure was measured for 48 h at
      baseline and again annually or more frequently (quarterly) if treatment
      adjustment was required. RESULTS: With data collected at baseline, when asleep
      blood pressure was adjusted by awake mean, only the former was a significant
      predictor of outcome in a Cox proportional hazards model also adjusted for sex,
      age, and diabetes. Analyses of changes in ambulatory blood pressure during follow
      up revealed a 17% reduction in cardiovascular risk for each 5-mm Hg decrease in
      asleep systolic blood pressure mean (p < 0.001), independently of changes in any
      other ambulatory blood pressure parameter. CONCLUSIONS: The sleep-time blood
      pressure mean is the most significant prognostic marker of cardiovascular
      morbidity and mortality. Most importantly, the progressive decrease in asleep
      blood pressure, a novel therapeutic target that requires proper patient
      evaluation by ambulatory monitoring, was the most significant predictor of event
      free survival. (Prognostic Value of Ambulatory Blood Pressure Monitoring in the
      Prediction of Cardiovascular Events and Effects of Chronotherapy in Relation to
      Risk [the MAPEC Study]; NCT00295542).

PMID- 21884957
TI  - Sleep-time blood pressure: a validated therapeutic target.

PMID- 21884958
TI  - Cardiorespiratory response to exercise after renal sympathetic denervation in
      patients with resistant hypertension.
AB  - OBJECTIVES: This study sought to investigate the effects of interventional renal
      sympathetic denervation (RD) on cardiorespiratory response to exercise.
      BACKGROUND: RD reduces blood pressure at rest in patients with resistant
      hypertension. METHODS: We enrolled 46 patients with therapy-resistant
      hypertension as extended investigation of the Symplicity HTN-2 (Renal Denervation
      With Uncontrolled Hypertension) trial. Thirty-seven patients underwent bilateral
      RD and 9 patients were assigned to the control group. Cardiopulmonary exercise
      tests were performed at baseline and 3-month follow-up. RESULTS: In the RD group,
      compared with baseline examination, blood pressure at rest and at maximum
      exercise after 3 months was significantly reduced by 31 +/- 13/9 +/- 13 mm Hg (p
      < 0.0001) and by 21 +/- 20/5 +/- 14 mm Hg (p < 0.0001), respectively. Achieved
      work rate increased by 5 +/- 13 W (p = 0.029) whereas peak oxygen uptake remained
      unchanged. Blood pressure 2 min after exercise was significantly reduced by 29 +/
      17/8 +/- 15 mm Hg (p < 0.001 for systolic blood pressure; p = 0.002 for
      diastolic blood pressure). Heart rate at rest decreased after RD (4 +/- 11
      beats/min; p = 0.028), whereas maximum heart rate and heart rate increase during
      exercise were not different. Heart rate recovery improved significantly by 4 +/-
      7 beats/min after renal denervation (p = 0.009). In the control group, there were
      no significant changes in blood pressure, heart rate, maximum work rate, or
      ventilatory parameters after 3 months. CONCLUSIONS: RD reduces blood pressure
      during exercise without compromising chronotropic competence in patients with
      resistant hypertension. Heart rate at rest decreased and heart rate recovery
      improved after the procedure. (Renal Denervation With Uncontrolled Hypertension;
      [Symplicity HTN-2]; NCT00888433).

PMID- 21884959
TI  - Predictors of in-hospital mortality in children after long-term ventricular
      assist device insertion.
AB  - OBJECTIVES: This study aimed to determine the pre-implantation predictors for in
      hospital mortality in children with ventricular assist device (VAD) support.
      BACKGROUND: Candidate selection is of critical importance for improved outcomes
      in patients supported with VAD. However, risk factors for post-VAD survival in
      children are still not clearly understood. METHODS: From June 1996 to December
      2009, 92 children underwent implantation of a long-term VAD at Germany Heart
      Institute Berlin. Data on all these patients were retrospectively analyzed, and
      pre-operative risk factors for in-hospital survival after VAD implantation were
      identified by multivariate logistic regression. RESULTS: Of the 92 subjects, the
      median age at implantation was 7 years (range 12 days to 18 years), and the
      median support time was 35 days (range 1 to 591 days). The overall survival rate
      to transplantation or recovery of ventricular function was 63%. Independent
      predictors of in-hospital mortality in children included congenital etiology
      (odds ratio [OR]: 11.2; 95% confidence interval [CI]: 2.6 to 47.5),
      norepinephrine requirement (OR: 6.9; 95% CI: 1.4 to 31), C-reactive protein level
      >6.3 mg/dl (OR: 4.9; 95% CI: 1.1 to 22.1), and central venous pressure >17 mm Hg
      (OR: 4.6; 95% CI: 1.1 to 20). CONCLUSIONS: Congenital etiology, pre-operative
      norepinephrine requirement, higher serum C-reactive protein, and central venous
      pressure were associated with increased in-hospital mortality in children with
      VAD support. Optimal candidate selection and timing of VAD insertion may be of
      great importance for improved outcomes in children with advanced heart failure.

PMID- 21884960
TI  - Dizziness and pre-syncope: an unusual clinical presentation of a spontaneous
      coronary artery dissection as revealed by optical coherence tomography.

PMID- 21884961
TI  - President's page: holding hands, sweaty palms, and silos.

PMID- 21884963
TI  - Late gadolinium enhancement and higher risk of arrhythmias: fibrosis or increased
      ventricular wall stress?

PMID- 21884964
TI  - Dynamic left ventricular outflow tract obstruction and acute heart failure in
      tako-tsubo cardiomyopathy.

PMID- 21884966
TI  - Molecular mechanisms of polycystic kidney disease.

PMID- 21884967
TI  - A pilot case-cohort study of liver and pancreatic cancers in poultry workers.
AB  - PURPOSE: To test the hypothesis that exposure to poultry oncogenic viruses that
      widely occurs occupationally in poultry workers and in the general population,
      may be associated with increased risks of deaths from liver and pancreatic
      cancers, and to identify new risk factors. METHODS: A pilot case-cohort study of
      both cancers within a combined cohort of 30,411 highly exposed poultry workers
      and 16,408 control subjects was conducted, and risk assessed by logistic
      regression odds ratios (OR) and proportional hazards risk ratios. RESULTS: New
      occupational findings were recorded respectively for pancreatic/liver cancers,
      for slaughtering of poultry (OR = 8.9, 95% confidence interval [CI]: 2.7-29.3)/OR
      = 9.1, 95% CI: 1.9-42.9); catching of live chickens (OR = 3.6, 95% CI: 1.2
      10.9)/OR = 1.0, 95% CI: 0.1-8.5); killing other types of animals for food (OR =
      4.8, 95% CI: 1.5-16.6)/OR = 2.0, 95% CI: 0.2-18.2), and ever worked on a pig
      raising farm (OR = 3.0, 95% CI: 1.0-8.2) for pancreatic cancer only. New non
      occupational findings for liver cancer were for receiving immunization with
      yellow fever vaccine (OR = 8.7, 95% CI: 1.0-76.3); and vaccination with typhoid
      vaccine (OR = 6.3, 95% CI: 1.1-37.4). The study also confirmed previously
      reported risk factors for both diseases. CONCLUSIONS: This study provides
      preliminary evidence that exposure to poultry oncogenic viruses may possibly be
      associated with the occurrence of liver and pancreatic cancers. Case-control
      studies nested within occupational cohorts of highly exposed subjects of
      sufficient statistical power may provide an efficient and valid method of
      investigating/confirming these findings.

PMID- 21884968
TI  - A correction factor for estimating statewide agricultural injuries from ambulance
      reports.
AB  - PURPOSE: Agriculture ranks as one of the most hazardous industries in the nation.
      Agricultural injury surveillance is critical to identifying and reducing major
      injury hazards. Currently, there is no comprehensive system of identifying and
      characterizing fatal and serious non-fatal agricultural injuries. Researchers
      sought to calculate a multiplier for estimating the number of agricultural injury
      cases based on the number of times the farm box indicator was checked on the
      ambulance report. METHODS: Farm injuries from 2007 that used ambulance transport
      were ascertained for 10 New York counties using two methods: (1) ambulance
      reports including hand-entered free text; and (2) community surveillance. The
      resulting multiplier that was developed from contrasting these two methods was
      then applied to the statewide Emergency Medical Services database to estimate the
      total number of agricultural injuries for New York state. RESULTS: There were
      25,735 unique ambulance runs due to injuries in the 10 counties in 2007. Among
      these, the farm box was checked a total of 90 times. Of these 90, 63 (70%) were
      determined to be agricultural. Among injury runs where the farm box was not
      checked, an additional 59 cases were identified from the free text. Among these
      122 cases (63 + 59), four were duplicates. Twenty-four additional unique cases
      were identified from the community surveillance for a total of 142. This yielded
      a multiplier of 142/90 = 1.578 for estimating all agricultural injuries from the
      farm box indicator. Sensitivity and specificity of the ambulance report method
      were 53.4% and 99.9%, respectively. CONCLUSIONS: This method provides a cost
      effective way to estimate the total number of agricultural injuries for the
      state. However, it would not eliminate the more labor intensive methods that are
      required to identify of the actual individual case records. Incorporating an
      independent source of case ascertainment (community surveillance) increased the
      multiplier by 17%.

PMID- 21884969
TI  - The photomorphogenic protein, DE-ETIOLATED 1, is a critical transcriptional
      corepressor in the central loop of the Arabidopsis circadian clock.
AB  - In this issue of Molecular Cell, Lau et al. (2011) demonstrate that DET1, a
      component of the COP10-DET1-DDB1 (CDD) complex, is a transcriptional corepressor
      recruited to the promoters of core clock genes via interaction with two MYB
      transcription factors, CCA1 and LHY.

PMID- 21884970
TI  - A new twist on clock protein phosphorylation: a conformational change leads to
      protein degradation.
AB  - Progressive phosphorylation of circadian clock proteins is a hallmark of time
      keeping. In this issue of Molecular Cell, Querfurth et al. (2011) demonstrate
      that phosphorylation of Neurospora FRQ induces a conformational change, which can
      account for its temporally gated degradation.

PMID- 21884971
TI  - HDAC3 at the fulcrum of an epithelial-mesenchymal balance.
AB  - In this issue of Molecular Cell, Wu et al. (2011) reveal an essential role for a
      chromatin modifier, histone deacetylase 3 (HDAC3), in hypoxia-induced epithelial
      mesenchymal transition (EMT); HIF-activated HDAC3 integrates with WDR5 to impose
      chromatin modifications that culminate in EMT.

PMID- 21884972
TI  - Translating a low-sugar diet into a longer life by maintaining thioredoxin
      peroxidase activity of a peroxiredoxin.
AB  - In this issue of Molecular Cell, Molin et al. (2011) reveal that caloric
      restriction alleviates PKA-dependent inhibition of sulfiredoxin translation,
      maintaining the thioredoxin peroxidase activity of a peroxiredoxin and increasing
      the hydrogen peroxide resistance and replicative life span of Saccharomyces
      cerevisiae.

PMID- 21884974
TI  - Circadian conformational change of the Neurospora clock protein FREQUENCY
      triggered by clustered hyperphosphorylation of a basic domain.
AB  - In the course of a day, the Neurospora clock protein FREQUENCY (FRQ) is
      progressively phosphorylated at up to 113 sites and eventually degraded.
      Phosphorylation and degradation are crucial for circadian time keeping, but it is
      not known how phosphorylation of a large number of sites correlates with
      circadian degradation of FRQ. We show that two amphipathic motifs in FRQ interact
      over a long distance, bringing the positively charged N-terminal portion in
      spatial proximity to the negatively charged middle and C-terminal portion of FRQ.
      The interaction is essential for the recruitment of casein kinase 1a (CK1a) into
      a stable complex with FRQ. FRQ-bound CK1a progressively phosphorylates the
      positively charged N-terminal domain of FRQ at up to 46 nonconsensus sites,
      triggering a conformational change, presumably by electrostatic repulsion, that
      commits the protein for degradation via the PEST1 signal in the negatively
      charged central portion of FRQ.

PMID- 21884973
TI  - Interaction of Arabidopsis DET1 with CCA1 and LHY in mediating transcriptional
      repression in the plant circadian clock.
AB  - The COP10-DET1-DDB1 (CDD) complex is an evolutionarily conserved protein complex
      discovered for its role in the repression of photomorphogenesis in Arabidopsis.
      It is important in many cellular and developmental processes in both plants and
      animals, but its molecular mode of action remains poorly understood. Here, we
      show that the CDD component DET1 possesses transcriptional repression activity
      and physically interacts with two closely related MYB transcription factors, CCA1
      and LHY, which are core components of the plant circadian clock. DET1 associates
      with the promoter of CCA1/LHY target genes, such as TOC1, in a CCA1/LHY-dependent
      manner and is required for their repression, suggesting a recruitment of DET1 by
      the central oscillator components to regulate the clock. Our results reveal DET1
      as a core transcriptional repression factor important for clock progression.
      Overall, the CDD complex may function as a transcriptional corepressor in diverse
      processes through direct interaction with distinct transcription factors.

PMID- 21884975
TI  - Rapid phospho-turnover by receptor tyrosine kinases impacts downstream signaling
      and drug binding.
AB  - Epidermal growth factor receptors (ErbB1-4) are oncogenic receptor tyrosine
      kinases (RTKs) that regulate diverse cellular processes. In this study, we
      combine measurement and mathematical modeling to quantify phospho-turnover at
      ErbB receptors in human cells and to determine the consequences for signaling and
      drug binding. We find that phosphotyrosine residues on ErbB1 have half-lives of a
      few seconds and therefore turn over 100-1000 times in the course of a typical
      immediate-early response to ligand. Rapid phospho-turnover is also observed for
      EGF-activated ErbB2 and ErbB3, unrelated RTKs, and multiple intracellular adaptor
      proteins and signaling kinases. Thus, the complexes formed on the cytoplasmic
      tail of active receptors and the downstream signaling kinases they control are
      highly dynamic and antagonized by potent phosphatases. We develop a kinetic
      scheme for binding of anti-ErbB1 drugs to receptors and show that rapid phospho
      turnover significantly impacts their mechanisms of action.

PMID- 21884976
TI  - Mechanisms underlying the dual-mode regulation of microtubule dynamics by
      Kip3/kinesin-8.
AB  - The kinesin-8 family of microtubule motors plays a critical role in microtubule
      length control in cells. These motors have complex effects on microtubule
      dynamics: they destabilize growing microtubules yet stabilize shrinking
      microtubules. The budding yeast kinesin-8, Kip3, accumulates on plus ends of
      growing but not shrinking microtubules. Here we identify an essential role of the
      tail domain of Kip3 in mediating both its destabilizing and its stabilizing
      activities. The Kip3 tail promotes Kip3's accumulation at the plus ends and
      facilitates the destabilizing effect of Kip3. However, the Kip3 tail also
      inhibits microtubule shrinkage and is required for promoting microtubule rescue
      by Kip3. These effects of the tail domain are likely to be mediated by the
      tubulin- and microtubule-binding activities that we describe. We propose a
      concentration-dependent model for the coordination of the destabilizing and
      stabilizing activities of Kip3 and discuss its relevance to cellular microtubule
      organization.

PMID- 21884977
TI  - A tethering mechanism controls the processivity and kinetochore-microtubule plus
      end enrichment of the kinesin-8 Kif18A.
AB  - Metaphase chromosome positioning depends on Kif18A, a kinesin-8 that accumulates
      at and suppresses the dynamics of K-MT plus ends. By engineering Kif18A mutants
      that suppress MT dynamics but fail to concentrate at K-MT plus ends, we identify
      a mechanism that allows Kif18A to accumulate at K-MT plus ends to a level
      required to suppress chromosome movements. Enrichment of Kif18A at K-MT plus ends
      depends on its C-terminal tail domain, while the ability of Kif18A to suppress MT
      growth is conferred by the N-terminal motor domain. The Kif18A tail contains a
      second MT-binding domain that diffuses along the MT lattice, suggesting that it
      tethers the motor to the MT track. Consistently, the tail enhances Kif18A
      processivity and is crucial for it to accumulate at K-MT plus ends. The
      heightened processivity of Kif18A, conferred by its tail domain, thus promotes
      concentration of Kif18A at K-MT plus ends, where it suppresses their dynamics to
      control chromosome movements.

PMID- 21884978
TI  - Mechanistic analysis of local ori melting and helicase assembly by the
      papillomavirus E1 protein.
AB  - Preparation of DNA templates for replication requires opening of the duplex to
      expose single-stranded (ss) DNA. The locally melted DNA is required for
      replicative DNA helicases to initiate unwinding. How local melting is generated
      in eukaryotic replicons is unknown, but initiator proteins from a handful of
      eukaryotic viruses can perform this function. Here we dissect the local melting
      process carried out by the papillomavirus E1 protein. We characterize the melting
      process kinetically and identify mutations in the E1 helicase and in the ori that
      arrest the local melting process. We show that a subset of these mutants have
      specific defects for melting of the center of the ori containing the binding
      sites for E1 and demonstrate that these mutants fail to untwist the ori DNA. This
      understanding of how E1 generates local melting suggests possible mechanisms for
      local melting in other replicons.

PMID- 21884979
TI  - NBS1 recruits RAD18 via a RAD6-like domain and regulates Pol eta-dependent
      translesion DNA synthesis.
AB  - Translesion DNA synthesis, a process orchestrated by monoubiquitinated PCNA, is
      critical for DNA damage tolerance. While the ubiquitin-conjugating enzyme RAD6
      and ubiquitin ligase RAD18 are known to monoubiquitinate PCNA, how they are
      regulated by DNA damage is not fully understood. We show that NBS1 (mutated in
      Nijmegen breakage syndrome) binds to RAD18 after UV irradiation and mediates the
      recruitment of RAD18 to sites of DNA damage. Disruption of NBS1 abolished RAD18
      dependent PCNA ubiquitination and Poleta focus formation, leading to elevated UV
      sensitivity and mutation. Unexpectedly, the RAD18-interacting domain of NBS1,
      which was mapped to its C terminus, shares structural and functional similarity
      with the RAD18-interacting domain of RAD6. These domains of NBS1 and RAD6 allow
      the two proteins to interact with RAD18 homodimers simultaneously and are crucial
      for Poleta-dependent UV tolerance. Thus, in addition to chromosomal break repair,
      NBS1 plays a key role in translesion DNA synthesis.

PMID- 21884980
TI  - Context-specific regulation of NF-kappaB target gene expression by EZH2 in breast
      cancers.
AB  - Both EZH2 and NF-kappaB contribute to aggressive breast cancer, yet whether the
      two oncogenic factors have functional crosstalk in breast cancer is unknown.
      Here, we uncover an unexpected role of EZH2 in conferring the constitutive
      activation of NF-kappaB target gene expression in ER-negative basal-like breast
      cancer cells. This function of EZH2 is independent of its histone
      methyltransferase activity but requires the physical interaction with RelA/RelB
      to promote the expression of NF-kappaB targets. Intriguingly, EZH2 acts
      oppositely in ER-positive luminal-like breast cancer cells and represses NF
      kappaB target gene expression by interacting with ER and directing repressive
      histone methylation on their promoters. Thus, EZH2 functions as a double-facet
      molecule in breast cancers, either as a transcriptional activator or repressor of
      NF-kappaB targets, depending on the cellular context. These findings reveal an
      additional mechanism by which EZH2 promotes breast cancer progression and
      underscore the need for developing context-specific strategy for therapeutic
      targeting of EZH2 in breast cancers.

PMID- 21884981
TI  - Interplay between HDAC3 and WDR5 is essential for hypoxia-induced epithelial
      mesenchymal transition.
AB  - Epithelial-mesenchymal transition (EMT) is important for organ development,
      metastasis, cancer stemness, and organ fibrosis. Molecular mechanisms to
      coordinately regulate hypoxia-induced EMT remain elusive. Here, we show that HIF
      1alpha-induced histone deacetylase 3 (hdac3) is essential for hypoxia-induced EMT
      and metastatic phenotypes. Change of specific chromatin states is associated with
      hypoxia-induced EMT. Under hypoxia, HDAC3 interacts with hypoxia-induced WDR5,
      recruits the histone methyltransferase (HMT) complex to increase histone H3
      lysine 4 (H3K4)-specific HMT activity, and activates mesenchymal gene expression.
      HDAC3 also serves as an essential corepressor to repress epithelial gene
      expression. Knockdown of WDR5 abolishes mesenchymal gene activation but not
      epithelial gene repression during hypoxia. These results indicate that hypoxia
      induces different chromatin modifiers to coordinately regulate EMT through
      distinct mechanisms.

PMID- 21884982
TI  - Life span extension and H(2)O(2) resistance elicited by caloric restriction
      require the peroxiredoxin Tsa1 in Saccharomyces cerevisiae.
AB  - Caloric restriction (CR) extends the life span of organisms ranging from yeast to
      primates. Here, we show that the thiol-dependent peroxiredoxin Tsa1 and its
      partner sulfiredoxin, Srx1, are required for CR to extend the replicative life
      span of yeast cells. Tsa1 becomes hyperoxidized/inactive during aging, and CR
      mitigates such oxidation by elevating the levels of Srx1, which is required to
      reduce/reactivate hyperoxidized Tsa1. CR, by lowering cAMP-PKA activity, enhances
      Gcn2-dependent SRX1 translation, resulting in increased resistance to H(2)O(2)
      and life span extension. Moreover, an extra copy of the SRX1 gene is sufficient
      to extend the life span of cells grown in high glucose concentrations by 20% in a
      Tsa1-dependent and Sir2-independent manner. The data demonstrate that Tsa1 is
      required to ensure yeast longevity and that CR extends yeast life span, in part,
      by counteracting age-induced hyperoxidation of this peroxiredoxin.

PMID- 21884983
TI  - A biotin switch-based proteomics approach identifies 14-3-3zeta as a target of
      Sirt1 in the metabolic regulation of caspase-2.
AB  - While lysine acetylation in the nucleus is well characterized, comparatively
      little is known about its significance in cytoplasmic signaling. Here we show
      that inhibition of the Sirt1 deacetylase, which is primarily cytoplasmic in
      cancer cell lines, sensitizes these cells to caspase-2-dependent death. To
      identify relevant Sirt1 substrates, we developed a proteomics strategy, enabling
      the identification of a range of putative substrates, including 14-3-3zeta, a
      known direct regulator of caspase-2. We show here that inhibition of Sirtuin
      activity accelerates caspase activation and overrides caspase-2 suppression by
      nutrient abundance. Furthermore, 14-3-3zeta is acetylated prior to caspase
      activation, and supplementation of Xenopus egg extract with glucose-6-phosphate,
      which promotes caspase-2/14-3-3zeta binding, enhances 14-3-3zeta-directed Sirtuin
      activity. Conversely, inhibiting Sirtuin activity promotes14-3-3zeta dissociation
      from caspase-2 in both egg extract and human cultured cells. These data reveal a
      role for Sirt1 in modulating apoptotic sensitivity, in response to metabolic
      changes, by antagonizing 14-3-3zeta acetylation.

PMID- 21884984
TI  - Cross-regulation between an alternative splicing activator and a transcription
      repressor controls neurogenesis.
AB  - Neurogenesis requires the concerted action of numerous genes that are regulated
      at multiple levels. However, how different layers of gene regulation are
      coordinated to promote neurogenesis is not well understood. We show that the
      neural-specific Ser/Arg repeat-related protein of 100 kDa (nSR100/SRRM4)
      negatively regulates REST (NRSF), a transcriptional repressor of genes required
      for neurogenesis. nSR100 directly promotes alternative splicing of REST
      transcripts to produce a REST isoform (REST4) with greatly reduced repressive
      activity, thereby activating expression of REST targets in neural cells.
      Conversely, REST directly represses nSR100 in nonneural cells to prevent the
      activation of neural-specific splicing events. Consistent with a critical role
      for nSR100 in the inhibition of REST activity, blocking nSR100 expression in the
      developing mouse brain impairs neurogenesis. Our results thus reveal a
      fundamental role for direct regulatory interactions between a splicing activator
      and transcription repressor in the control of the multilayered regulatory
      programs required for neurogenesis.

PMID- 21884998
TI  - Current and future strategies for antiangiogenic agents in non-small-cell lung
      cancer.

PMID- 21884999
TI  - Optimizing the dose and schedule of anti-vascular endothelial growth factor
      antibodies in non-small-cell lung cancer.
AB  - Lung cancer is the world's leading cause of cancer death. Most patients with non
      small-cell lung cancer (NSCLC) present with advanced disease. Median survival is
      approximately 8-10 months for patients who receive standard platinum-based
      doublet therapy. In 2006 the FDA approved the anti-vascular endothelial growth
      factor (VEGF) antibody bevacizumab for patients with advanced, non-squamous,
      NSCLC based on the Eastern Cooperative Oncology Group E4599 trial. This trial
      demonstrated a 2-month improvement in overall survival when bevacizumab was added
      to carboplatin/paclitaxel. European investigators presented further data
      supporting improvement in progression-free survival with the use of bevacizumab
      and a cisplatin doublet in the Avastin in Lung Cancer (AVAiL) trial. Bevacizumab
      at doses of 7.5 mg/kg and 15 mg/kg are both effective and safe for patients with
      advanced NSCLC. Fatal hemorrhage has been reported for patients receiving the
      antiangiogenesis antibody. According to a retrospective study, the only
      significant clinical and radiographic variable associated with increased risk of
      pulmonary hemorrhage is the presence of cavitation. Common side effects include
      hypertension, proteinuria and minor mucosal bleeding. Bevacizumab monotherapy
      given every 21 days can be safely continued for patients without evidence of
      progression and for whom side effects of therapy are acceptable. Many questions
      remain, such as the role of the anti-VEGF antibody in early-stage disease, the
      safety of bevacizumab in patients with squamous histology NSCLC, and the benefit
      of combination therapy in elderly patients.

PMID- 21885000
TI  - Treatment of patients excluded from Eastern Cooperative Oncology Group 4599 and
      AVAiL studies: focus on brain metastasis and squamous histology.
AB  - Bevacizumab is the first molecularly targeted agent associated with improved
      outcomes in combination with chemotherapy in previously untreated patients with
      non-small-cell lung cancer (NSCLC). The addition of bevacizumab, a monoclonal
      antibody against vascular endothelial growth factor (VEGF), to carboplatin and
      paclitaxel resulted in a significant improvement in overall survival compared
      with chemotherapy alone; however, bevacizumab is associated with increased risk
      of severe complications, including hemoptysis, neutropenic fever, and
      gastrointestinal perforation. Based on the initial observations that patients
      with squamous cell carcinoma treated with bevacizumab are at high risk for severe
      and fatal hemoptysis, these patients were not included in subsequent phase III
      clinical trials involving this agent. Patients with known brain metastases from
      lung cancer were excluded because of concern for intracranial bleeding.
      Consequently, nearly half the patients with newly diagnosed metastatic NSCLC are
      not treated with bevacizumab because of squamous histology or the presence of
      brain metastasis. This review provides a brief overview of the very limited data
      available regarding the safety and efficacy of bevacizumab and other VEGF
      inhibitors in patients with squamous cell histology or brain metastasis and
      current ongoing research efforts.

PMID- 21885001
TI  - Emerging safety data for bevacizumab in advanced non-small-cell lung cancer.
AB  - Bevacizumab, a monoclonal antibody to vascular endothelial growth factor, confers
      improved clinical outcomes in a range of tumor types when administered in
      combination with chemotherapy. In a pivotal phase III trial (E4599), bevacizumab
      became the first agent to extend overall survival beyond 1 year when combined
      with first-line chemotherapy for advanced, metastatic, or recurrent non-squamous
      non-small-cell lung cancer (NSCLC). In a recent phase III trial (AVAiL; Avastin
      in Lung Cancer), which investigated the safety and efficacy of 2 bevacizumab
      doses in combination with cisplatin/gemcitabine, bevacizumab-based therapy
      significantly delayed disease progression in patients with advanced, metastatic,
      or recurrent non-squamous NSCLC. Based on these positive data, bevacizumab in
      combination with chemotherapy has received US and European Union approval for the
      first-line treatment of unresectable advanced, metastatic, or recurrent
      predominantly non-squamous NSCLC. Bevacizumab-based therapy has a well
      characterized safety profile. Clinically relevant bevacizumab-associated adverse
      events reported in clinical trials to date include bleeding, hypertension,
      proteinuria, thrombotic events, wound-healing complications, and gastrointestinal
      perforations. Emerging safety data for bevacizumab in NSCLC from the recent AVAiL
      trial indicate that, as in clinical trials in other indications, adverse events
      were generally manageable using standard clinical techniques and rarely required
      discontinuation of bevacizumab therapy. In the AVAiL trial, grade >= 3
      hypertension, bleeding, and proteinuria rates were modestly higher in the
      bevacizumab arms than in the placebo arm, although the overall incidence of grade
      >= 3 adverse events was similar in the placebo and bevacizumab arms.
      Recommendations for the monitoring and management of bevacizumab-associated
      adverse events are discussed.

PMID- 21885002
TI  - Ongoing trials with bevacizumab and other antiangiogenic agents in lung cancer.
AB  - The recent approval of bevacizumab, sunitinib, and sorafenib in a number of
      diseases has led to significant interest in expanding the role of antiangiogenic
      therapies in cancer. Specifically, bevacizumab has only received approval for a
      relatively selective population with advanced non-squamous non-small-cell lung
      cancer (NSCLC) with good performance status and without coagulopathy, brain
      metastases, or hemoptysis. This has significantly restricted the potential
      benefit bevacizumab can bring to patients with lung cancer. In order to address
      whether bevacizumab might be beneficial in other settings, a multitude of
      clinical trials are ongoing. These include questions such as the safety of
      bevacizumab in patients with hemoptysis, brain metastases, and squamous cell
      histology. The use of bevacizumab is also being addressed in locally advanced and
      early-stage lung cancer. The results of many of these trials will be available in
      the next 2-3 years. Unfortunately, as in the case of many targeted therapies, we
      lack a specific biomarker to predict response to these agents. In addition,
      although antiangiogenic trials are well under way in NSCLC, this is not the case
      for small-cell lung cancer, a highly angiogenic disease in which the pace of
      research is substantially slower.

PMID- 21885003
TI  - Can we customize chemotherapy? Individualizing cytotoxic regimens in advanced non
      small-cell lung cancer.
AB  - Metastatic non-small-cell lung cancer remains a fatal disease with a median
      survival of < 1 year. A critical challenge is to develop predictive markers for
      customizing platinum-based treatment. The first studies focused on the excision
      repair cross-complementing 1 (ERCC1) gene in this difficult task. Several layers
      of evidence indicate that ERCC1 mRNA expression could be a predictive marker for
      cisplatin alone or in combination with certain drugs such as etoposide,
      gemcitabine, and 5-fluorouracil but not in combination with antimicrotubule
      drugs. Several retrospective studies demonstrated an impressive survival
      advantage for gemcitabine plus cisplatin but not for other combinations in tumors
      with low ERCC1 expression. A customized phase III ERCC1-based trial met the
      primary endpoint of improvement in response but not in survival, leading us to
      hypothesize that docetaxel might not be the most appropriate partner for
      cisplatin in the presence of low ERCC1 levels or for gemcitabine in the presence
      of high ERCC1 levels. A phase II study demonstrated the feasibility of combining
      carboplatin, gemcitabine, docetaxel, and vinorelbine according to ERCC1 and
      ribonucleotide reductase subunit M1 expression levels. These findings highlight
      the importance of continual learning, and decision-making strategies for
      customizing treatment should reflect the limitations of our knowledge.

PMID- 21885010
TI  - [RICIBA (Computerized registry of bariatric surgery ), what do we know about
      bariatric surgery in Spain?].

PMID- 21885011
TI  - A web of imprinting in stem cells.
AB  - Imprinted genes are the prototypical epigenetically regulated genes. On the basis
      of findings in adult lung stem cells, Zacharek et al. (2011) suggest in this
      issue of Cell Stem Cell that epigenetic silencing of imprinted genes is a common
      requirement for maintaining self-renewal in adult stem cell populations.

PMID- 21885012
TI  - Converting human skin cells to neurons: a new tool to study and treat brain
      disorders?
AB  - Recent publications in Cell Stem Cell (Son et al., 2011; Ambasudhan et al.,
      2011), PNAS (Pfisterer et al., 2011), and Nature (Caiazzo et al., 2011; Pang et
      al., 2011; Yoo et al., 2011) report that functional neurons can be directly
      generated from human fibroblast cells without going through the pluripotent
      state.

PMID- 21885013
TI  - FoxO: a new addition to the ESC cartel.
AB  - The forkhead box O (FoxO) family is involved in diverse cellular processes such
      as tumor suppression, stress response, and metabolism. In a recent Nature Cell
      Biology Letter, Zhang et al. (2011) uncover a novel role for FoxO proteins in
      regulating the identity of human ESCs.

PMID- 21885014
TI  - Committing to a hairy fate: epigenetic regulation of hair follicle stem cells.
AB  - Chromatin modifications are important for embryonic stem cell (ESC) pluripotency,
      but their functions in adult stem cells are less clear. In this issue of Cell
      Stem Cell, Lien et al. (2011) delineate histone methylation patterns in hair
      follicle stem cells and show that these marks differ from those of ESCs.

PMID- 21885015
TI  - Leukemia stemness signatures step toward the clinic.
AB  - A recent Nature Medicine study by Eppert et al. (2011) describes analyses of
      functionally defined leukemia stem cell populations that provide new insights on
      the biology of human tumor populations and the potential use of stem cell
      associated gene signatures for prognosis.

PMID- 21885016
TI  - Breaking the cell cycle of HSCs by p57 and friends.
AB  - The cell cycle regulators involved in maintaining the quiescence, and thereby the
      self-renewal capacity, of somatic stem cells have long been elusive. Two new Cell
      Stem Cell articles in this issue (Matsumoto et al., 2011; Zou et al., 2011) now
      show that the CDK inhibitor p57 is a crucial brake for cycling HSCs, and links
      self-renewal activity to cell cycle quiescence.

PMID- 21885017
TI  - TET family proteins and their role in stem cell differentiation and
      transformation.
AB  - One of the main regulators of gene expression during embryogenesis and stem cell
      differentiation is DNA methylation. The recent identification of
      hydroxymethylcytosine (5hmC) as a novel epigenetic mark sparked an intense effort
      to characterize its specialized enzymatic machinery and to understand the
      biological significance of 5hmC. The recent discovery of recurrent deletions and
      somatic mutations in the TET gene family, which includes proteins that can
      hydroxylate methylcytosine (5mC), in a large fraction of myeloid malignancies
      further suggested a key role for dynamic DNA methylation changes in the
      regulation of stem cell differentiation and transformation.

PMID- 21885018
TI  - Genome-wide maps of histone modifications unwind in vivo chromatin states of the
      hair follicle lineage.
AB  - Using mouse skin, where bountiful reservoirs of synchronized hair follicle stem
      cells (HF-SCs) fuel cycles of regeneration, we explore how adult SCs remodel
      chromatin in response to activating cues. By profiling global mRNA and chromatin
      changes in quiescent and activated HF-SCs and their committed, transit-amplifying
      (TA) progeny, we show that polycomb-group (PcG)-mediated H3K27-trimethylation
      features prominently in HF-lineage progression by mechanisms distinct from
      embryonic-SCs. In HF-SCs, PcG represses nonskin lineages and HF differentiation.
      In TA progeny, nonskin regulators remain PcG-repressed, HF-SC regulators acquire
      H3K27me3-marks, and HF-lineage regulators lose them. Interestingly, genes poised
      in embryonic stem cells, active in HF-SCs, and PcG-repressed in TA progeny encode
      not only key transcription factors, but also signaling regulators. We document
      their importance in balancing HF-SC quiescence, underscoring the power of
      chromatin mapping in dissecting SC behavior. Our findings explain how HF-SCs
      cycle through quiescent and activated states without losing stemness and define
      roles for PcG-mediated repression in governing a fate switch irreversibly.

PMID- 21885019
TI  - Regulation of human epidermal stem cell proliferation and senescence requires
      polycomb- dependent and -independent functions of Cbx4.
AB  - Human epidermal stem cells transit from a slow cycling to an actively
      proliferating state to contribute to homeostasis. Both stem cell states differ in
      their cell cycle profiles but must remain guarded from differentiation and
      senescence. Here we show that Cbx4, a Polycomb Repressive Complex 1 (PRC1)
      associated protein, maintains human epidermal stem cells as slow-cycling and
      undifferentiated, while protecting them from senescence. Interestingly,
      abrogating the polycomb activity of Cbx4 impairs its antisenescent function
      without affecting stem cell differentiation, indicating that differentiation and
      senescence are independent processes in human epidermis. Conversely, Cbx4
      inhibits stem cell activation and differentiation through its SUMO ligase
      activity. Global transcriptome and chromatin occupancy analyses indicate that
      Cbx4 regulates modulators of epidermal homeostasis and represses factors such as
      Ezh2, Dnmt1, and Bmi1 to prevent the active stem cell state. Our results suggest
      that distinct Polycomb complexes balance epidermal stem cell dormancy and
      activation, while continually preventing senescence and differentiation.

PMID- 21885020
TI  - p57(Kip2) and p27(Kip1) cooperate to maintain hematopoietic stem cell quiescence
      through interactions with Hsc70.
AB  - Cell cycle regulators play critical roles in the balance between hematopoietic
      stem cell (HSC) dormancy and proliferation. In this study, we report that cell
      cycle entry proceeded normally in HSCs null for cyclin-dependent kinase (CDK)
      inhibitor p57 due to compensatory upregulation of p27. HSCs null for both p57 and
      p27, however, were more proliferative and had reduced capacity to engraft in
      transplantation. We found that heat shock cognate protein 70 (Hsc70) interacts
      with both p57 and p27 and that the subcellular localization of Hsc70 was critical
      to maintain HSC cell cycle kinetics. Combined deficiency of p57 and p27 in HSCs
      resulted in nuclear import of an Hsc70/cyclin D1 complex, concomitant with Rb
      phosphorylation, and elicited severe defects in maintaining HSC quiescence. Taken
      together, these data suggest that regulation of cytoplasmic localization of
      Hsc70/cyclin D1 complex by p57 and p27 is a key intracellular mechanism in
      controlling HSC dormancy.

PMID- 21885021
TI  - p57 is required for quiescence and maintenance of adult hematopoietic stem cells.
AB  - Quiescence is required for the maintenance of hematopoietic stem cells (HSCs).
      Members of the Cip/Kip family of cyclin-dependent kinase (CDK) inhibitors (p21,
      p27, p57) have been implicated in HSC quiescence, but loss of p21 or p27 in mice
      affects HSC quiescence or functionality only under conditions of stress. Although
      p57 is the most abundant family member in quiescent HSCs, its role has remained
      uncharacterized. Here we show a severe defect in the self-renewal capacity of p57
      deficient HSCs and a reduction of the proportion of the cells in G(0) phase.
      Additional ablation of p21 in a p57-null background resulted in a further
      decrease in the colony-forming activity of HSCs. Moreover, the HSC abnormalities
      of p57-deficient mice were corrected by knocking in the p27 gene at the p57
      locus. Our results therefore suggest that, among Cip/Kip family CDK inhibitors,
      p57 plays a predominant role in the quiescence and maintenance of adult HSCs.

PMID- 21885023
TI  - [Splenic marginal zone B-cell lymphoma with epidermotropic skin involvement].
AB  - Marginal zone B-cell lymphoma (MZL) is subclassified into extranodal MZL of
      mucosa-associated lymphoid tissue (including cutaneous lymphomas), splenic MZL,
      and nodal MZL. We report the case of a 68-year-old man with erythematous
      violaceous plaques and nodules. Skin biopsy showed an epidermotropic lymphocytic
      infiltration and cytology and immunohistochemistry were consistent with MZL. The
      workup revealed disease in the peripheral blood and bone marrow and massive
      splenomegaly. Splenectomy confirmed the diagnosis of splenic MZL and led to
      resolution of the skin lesions. Cutaneous recurrence was treated successfully
      with chemotherapy and rituximab but caused fatal hepatitis due to hepatitis B
      virus reactivation. Skin involvement by splenic MZL is uncommon; this form of the
      disease can present epidermotropism, a very rare finding in primary cutaneous
      MZL. Treatment consists of splenectomy, which may be associated with chemotherapy
      and/or rituximab; this treatment may lead to reactivation of latent hepatitis B
      infection and screening for hepatitis should therefore be performed prior to
      starting therapy.

PMID- 21885022
TI  - Lung stem cell self-renewal relies on BMI1-dependent control of expression at
      imprinted loci.
AB  - BMI1 is required for the self-renewal of stem cells in many tissues including the
      lung epithelial stem cells, Bronchioalveolar Stem Cells (BASCs). Imprinted genes,
      which exhibit expression from only the maternally or paternally inherited allele,
      are known to regulate developmental processes, but what their role is in adult
      cells remains a fundamental question. Many imprinted genes were derepressed in
      Bmi1 knockout mice, and knockdown of Cdkn1c (p57) and other imprinted genes
      partially rescued the self-renewal defect of Bmi1 mutant lung cells. Expression
      of p57 and other imprinted genes was required for lung cell self-renewal in
      culture and correlated with repair of lung epithelial cell injury in vivo. Our
      data suggest that BMI1-dependent regulation of expressed alleles at imprinted
      loci, distinct from imprinting per se, is required for control of lung stem
      cells. We anticipate that the regulation and function of imprinted genes is
      crucial for self-renewal in diverse adult tissue-specific stem cells.

PMID- 21885024
TI  - [Unsuspected visceral leishmaniasis infiltrating a squamous cell carcinoma].
AB  - Amastigotes of the genus Leishmania have been observed in biopsies of apparently
      unrelated lesions in patients with AIDS and visceral leishmaniasis. We describe
      the case of a 40-year-old man with human immunodeficiency virus infection and
      severe immunodepression in whom the presence of the parasite was detected as an
      incidental finding on histological study of a perianal squamous cell carcinoma.
      This finding led to the diagnosis and subsequent treatment of previously
      unsuspected visceral leishmaniasis. In a review of the literature we have found
      no previous examples of this association.

PMID- 21885025
TI  - [Localized primary cutaneous nodular amyloidosis in a patient with
      paraproteinemia].

PMID- 21885026
TI  - [Telangiectatic macules in a 90-year-old woman].

PMID- 21885027
TI  - [Mycobacterium chelonae infection in a patient being treated with adalimumab].

PMID- 21885028
TI  - Mutations causing familial biparental hydatidiform mole implicate c6orf221 as a
      possible regulator of genomic imprinting in the human oocyte.
AB  - Familial biparental hydatidiform mole (FBHM) is the only known pure maternal
      effect recessive inherited disorder in humans. Affected women, although
      developmentally normal themselves, suffer repeated pregnancy loss because of the
      development of the conceptus into a complete hydatidiform mole in which
      extraembryonic trophoblastic tissue develops but the embryo itself suffers early
      demise. This developmental phenotype results from a genome-wide failure to
      correctly specify or maintain a maternal epigenotype at imprinted loci. Most
      cases of FBHM result from mutations of NLRP7, but genetic heterogeneity has been
      demonstrated. Here, we report biallelic mutations of C6orf221 in three families
      with FBHM. The previously described biological properties of their respective
      gene families suggest that NLRP7 and C6orf221 may interact as components of an
      oocyte complex that is directly or indirectly required for determination of
      epigenetic status on the oocyte genome.

PMID- 21885029
TI  - A general framework for detecting disease associations with rare variants in
      sequencing studies.
AB  - Biological and empirical evidence suggests that rare variants account for a large
      proportion of the genetic contributions to complex human diseases. Recent
      technological advances in high-throughput sequencing platforms have made it
      possible for researchers to generate comprehensive information on rare variants
      in large samples. We provide a general framework for association testing with
      rare variants by combining mutation information across multiple variant sites
      within a gene and relating the enriched genetic information to disease phenotypes
      through appropriate regression models. Our framework covers all major study
      designs (i.e., case-control, cross-sectional, cohort and family studies) and all
      common phenotypes (e.g., binary, quantitative, and age at onset), and it allows
      arbitrary covariates (e.g., environmental factors and ancestry variables). We
      derive theoretically optimal procedures for combining rare mutations and
      construct suitable test statistics for various biological scenarios. The allele
      frequency threshold can be fixed or variable. The effects of the combined rare
      mutations on the phenotype can be in the same direction or different directions.
      The proposed methods are statistically more powerful and computationally more
      efficient than existing ones. An application to a deep-resequencing study of drug
      targets led to a discovery of rare variants associated with total cholesterol.
      The relevant software is freely available.

PMID- 21885030
TI  - High myopia caused by a mutation in LEPREL1, encoding prolyl 3-hydroxylase 2.
AB  - Autosomal-recessive high-grade axial myopia was diagnosed in Bedouin Israeli
      consanguineous kindred. Some affected individuals also had variable expressivity
      of early-onset cataracts, peripheral vitreo-retinal degeneration, and secondary
      sight loss due to severe retinal detachments. Through genome-wide linkage
      analysis, the disease-associated gene was mapped to ~1.7 Mb on chromosome 3q28
      (the maximum LOD score was 11.5 at theta = 0 for marker D3S1314). Sequencing of
      the entire coding regions and intron-exon boundaries of the six genes within the
      defined locus identified a single mutation (c.1523G>T) in exon 10 of LEPREL1,
      encoding prolyl 3-hydroxylase 2 (P3H2), a 2-oxoglutarate-dependent dioxygenase
      that hydroxylates collagens. The mutation affects a glycine that is conserved
      within P3H isozymes. Analysis of wild-type and p.Gly508Val (c.1523G>T) mutant
      recombinant P3H2 polypeptides expressed in insect cells showed that the mutation
      led to complete inactivation of P3H2.

PMID- 21885031
TI  - [Rheumatoid arthritis: a cardiovascular disease?].
AB  - Mortality in rheumatoid arthritis (RA) is doubled when compared to the general
      population. This excess in mortality can be explained in half of cases by
      cardiovascular (CV) events. The risk of myocardial infarction is increased by
      about 60% in RA. Mortality secondary to cerebrovascular stroke is increased by
      50% even if the incidence of stroke is not increased. Indeed, the risk of fatal
      CV events is increased in RA when compared to the general population. The
      increased CV risk cannot be explained only by traditional CV risk factors, even
      if smoking and changes in lipid profile may be implied. It is mainly related to
      the chronic inflammatory condition that causes many metabolic disturbances. Other
      parameters such as treatments used in RA also play a role. Thus, it is essential
      for proper management of RA patients to be aware of this risk and to treat any
      modifiable CV risk factors.

PMID- 21885032
TI  - PERIOSTIN regulates MMP-2 expression via the alphavbeta3 integrin/ERK pathway in
      human periodontal ligament cells.
AB  - OBJECTIVE: During orthodontic tooth movement, activation of the vascular system
      in the compressed periodontal ligament (PDL), which becomes hypoxic, is essential
      for periodontal tissue remodelling. PERIOSTIN, an extracellular matrix protein,
      is expressed in PDL and its concentration is increased on the compressive side
      during orthodontic tooth movement. PERIOSTIN promotes angiogenesis through
      upregulation of matrix metalloproteinase (MMP)-2, which has been shown to be
      expressed via alphavbeta3 integrin/extracellular signal-related kinase (ERK)
      signalling pathway and vascular endothelial growth factor (VEGF). Therefore, we
      hypothesized that hypoxia-induced PERIOSTIN promotes MMP-2 expression via
      alphavbeta3 integrin/ERK signalling and VEGF in PDL cells. METHODS: Human PDL
      cells were cultured in condition medium containing desferrioxamine (DFO) to mimic
      hypoxia. The total RNA, cell lysates or supernatant were collected, and MMP2 and
      VEGF expression, PERIOSTIN expression and ERK phosphorylation, and MMP-2 activity
      were analysed by real-time RT-PCR, western blot analysis, and zymography,
      respectively. A recombinant human PERIOSTIN or PERIOSTIN siRNA was applied to the
      cells, then the total RNA was extracted to measure MMP-2 and VEGF expression. The
      cells were treated with alphavbeta3 integrin-blocking antibody or ERK inhibitor
      followed by PERIOSTIN stimulation. MMP-2 expression was measured by real-time RT
      PCR. RESULTS: PERIOSTIN was upregulated in a time-dependent manner in human PDL
      cells treated with DFO, a chemical hypoxia mimic. MMP-2 and VEGF expression, and
      MMP-2 activity were increased by DFO or PERIOSTIN treatment, and decreased by
      PERIOSTIN silencing. PERIOSTIN treatment also induced ERK phosphorylation, and
      PERIOSTIN-induced MMP-2 was reduced by alphavbeta3 integrin-blocking antibody or
      ERK inhibitor. CONCLUSION: These data suggest that PERIOSTIN upregulates MMP-2
      expression via the alphavbeta3 integrin/ERK signalling pathway and VEGF
      expression in human PDL cells.

PMID- 21885033
TI  - Salivary beta-galactosidase activity affects physiological oral malodour.
AB  - OBJECTIVES: Previous reports have associated salivary beta-galactosidase activity
      with non-periodontopathic oral malodour. In this study, we investigated the
      localization of beta-galactosidase and elucidated the relationship between its
      enzymatic activity and physiological oral malodour. STUDY DESIGN: Fifty-six
      patients complaining of halitosis were separated into two groups: periodontally
      healthy and periodontitis. Saliva samples from the subjects were separated by
      centrifugation, and the level of beta-galactosidase activity was measured in the
      supernatant, pellet lysate, and whole saliva using the chromogenic substrate o
      nitrophenyl-beta-d-galactopyranoside. The correlation of salivary beta
      galactosidase activity with breath odour and associated parameters was examined.
      RESULTS: Similar levels of beta-galactosidase activity were detected in the
      pellet lysate and whole saliva, but not in the saliva supernatant. Positive
      correlations were observed between the beta-galactosidase activity in whole
      saliva and oral malodour levels in the periodontally healthy group, but not in
      the periodontitis group. In addition, the plaque index and tongue coating score
      were positively correlated with beta-galactosidase activity in the periodontally
      healthy group. Overall, stimulated salivary flow and salivary pH were negatively
      correlated with enzyme activity. The amounts of total bacteria, Fusobacterium
      nucleatum, and Streptococcus salivarius were positively associated with beta
      galactosidase activity in the periodontally healthy group. Furthermore, the
      amounts of total bacteria and S. salivarius were positively associated with the
      amount of volatile sulphur compounds. CONCLUSIONS: Our results indicate that beta
      galactosidase is located on the cell surface of oral bacteria derived from dental
      plaque and tongue coating, and it plays an important role in producing the
      malodour underlying physiological oral malodour.

PMID- 21885034
TI  - Acceptance and values-based action in chronic pain: a three-year follow-up
      analysis of treatment effectiveness and process.
AB  - Recent developments in CBT emphasize the promotion of psychological flexibility
      to improve daily functioning for people with a wide range of health conditions.
      In particular, one of these approaches, Acceptance and Commitment Therapy (ACT),
      has been studied for treatment of chronic pain. While trials have provided good
      support for treatment effectiveness through follow-ups of as long as seven
      months, the longer-term impact is not known. The present study of 108
      participants with chronic pain examined outcomes three years after treatment
      completion and included analyses of two key treatment processes, acceptance of
      pain and values-based action. Overall, results indicated significant improvements
      in emotional and physical functioning relative to the start of treatment, as well
      as good maintenance of treatment gains relative to an earlier follow-up
      assessment. Effect size statistics were generally medium or large. At the three
      year follow-up, 64.8% of patients had reliably improved in at least one key
      domain. Improvements in acceptance of pain and values-based action were
      associated with improvements in outcome measures. A "treatment responder"
      analysis, using variables collected at pre-treatment and shorter term follow-up,
      failed to identify any salient predictors of response. This study adds to the
      growing literature supporting the effectiveness of ACT for chronic pain and
      yields evidence for both statistical and clinical significance of improvements
      over a three-year period.

PMID- 21885036
TI  - Visual acuity in adults with Asperger's syndrome: no evidence for "eagle-eyed"
      vision.
AB  - BACKGROUND: Autism spectrum conditions (ASC) are defined by criteria comprising
      impairments in social interaction and communication. Altered visual perception is
      one possible and often discussed cause of difficulties in social interaction and
      social communication. Recently, Ashwin et al. suggested that enhanced ability in
      local visual processing in ASC was due to superior visual acuity, but that study
      has been the subject of methodological criticism, placing the findings in doubt.
      METHODS: The present study investigated visual acuity thresholds in 24 adults
      with Asperger's syndrome and compared their results with 25 control subjects with
      the 2 Meter 2000 Series Revised ETDRS Chart. RESULTS: The distribution of visual
      acuities within the two groups was highly similar, and none of the participants
      had superior visual acuity. CONCLUSIONS: Superior visual acuity in individuals
      with Asperger's syndrome could not be established, suggesting that differences in
      visual perception in ASC are not explained by this factor. A continued search for
      explanations of superior ability in local visual processing in persons with ASC
      is therefore warranted.

PMID- 21885037
TI  - RACK1 affects morphine reward via BDNF.
AB  - Chronic morphine addiction may trigger functional changes in the mesolimbic
      dopamine system, which is believed to be the neurobiological substrate of opiate
      addiction. Brain derived neurotrophic factor (BDNF) has been implicated in
      addiction-related pathology in animal studies. Our previous studies have shown
      that RACK1 is involved in morphine reward in mice. The recent research indicates
      nuclear RACK1 by localizing at the promoter IV region of the BDNF gene and the
      subsequent chromatin modifications leads to the activation of the promoter and
      transcription of BDNF. The present study was designed to investigate if shRACK1
      (a short hairpin RNA of RACK1) could reverse the mice's behavioral responses to
      morphine and BDNF expression in hippocampus and prefrontal cortex. No significant
      changes were observed in vehicle-infused mice which received no morphine
      treatment (CONC) and shRACK1-infused mice which received no morphine treatment
      (CONR), whereas vehicle-infused mice preceded the morphine injection (MIC) showed
      increased BDNF expression in hippocampus and prefrontal cortex, as compared to
      vehicle-infused mice which received no morphine treatment (CONC).
      Intracerebroventricular shRACK1 treatment reversed these, and in fact, ShRACK1
      infused mice preceded the morphine injection (MIR) showed reduced BDNF expression
      in hippocampus and prefrontal cortex, as compared to MIC. In the conditioned
      place preference (CPP) test, inactivating RACK1 markedly reduces morphine-induced
      conditioned place preference. Non-specific changes in CPP could not account for
      these effects since general CPP of shRACK1- and vehicle-infused animals was not
      different. Combined behavioral and molecular approaches have support the
      possibility that the RACK1-BDNF system plays an important role in the response to
      morphine-induced reward.

PMID- 21885038
TI  - TASK-3 as a potential antidepressant target.
AB  - Modulation of TASK-3 (Kcnk9) potassium channels affect neurotransmitter release
      in thalamocortical centers and other sleep-related nuclei having the capacity to
      regulate arousal cycles and REM sleep changes associated with mood disorders and
      antidepressant action. Circumstantial evidence from this and previous studies
      suggest the potential for TASK-3 to be a novel antidepressant therapeutic target;
      TASK-3 knock-out mice display augmented circadian amplitude and exhibit sleep
      architecture characterized by suppressed REM activity. Detailed analysis of
      locomotor activity indicates that the amplitudes of activity bout duration and
      bout number are augmented in TASK-3 mutants well beyond that seen in wildtypes,
      findings substantiated by amplitude increases in body temperature and EEG
      recordings of sleep stage bouts. Polysomnographic analysis of TASK-3 mutants
      reveals increases in nocturnal active wake and suppressed REM sleep time while
      increased slow wave sleep typifies the inactive phase, findings that have
      implications for the cognitive impact of reduced TASK-3 activity. In direct
      measures of their resistance to despair behavior, TASK-3 knock-outs displayed
      significant decreases in immobility relative to wildtype controls in both tail
      suspension and forced swim tests. Treatment of wildtype animals with the
      antidepressant Fluoxetine markedly reduced REM sleep, while leaving active wake
      and slow wave sleep relatively intact. Remarkably, these effects were absent in
      TASK-3 mutants indicating that TASK-3 is either directly involved in the
      mechanism of this drug's action, or participates in parallel pathways that
      achieve the same effect. Together, these results support the TASK-3 channel to
      act as a therapeutic target for antidepressant action.

PMID- 21885039
TI  - Impact of environmental enrichment on neurogenesis in the dentate gyrus during
      the early postnatal period.
AB  - Accumulating evidence shows that environmental enrichment increases neurogenesis
      in the adult hippocampal dentate gyrus. The goal of the current study was to
      examine the effect of environmental enrichment on hippocampal neurogenesis during
      early life stages. We used as an animal model the guinea pig, a precocious rodent
      that is early independent from maternal care. Animals were assigned to either a
      standard (control) or an enriched environment a few days after birth (P5-P6).
      Between P14 and P17 animals received one daily bromodeoxyuridine (BrdU)
      injection, to label dividing cells, and were sacrificed either on P18, to
      evaluate cell proliferation or on P45, to evaluate cell survival and
      differentiation. In 18-day old enriched animals, there was a larger number of
      BrdU-positive cells compared to that found in controls. At P45, enriched animals
      had more surviving cells and more cells with a neuronal phenotype than controls.
      Unbiased stereology revealed that enriched animals had more granule cells (+37%
      at P18 and +31% at P45). Results show that environmental enrichment in the early
      postnatal period notably increases cell proliferation and survival, with a large
      increase in the number of neurons forming the granule cell layer. The impact of
      environmental enrichment in the early postnatal period emphasizes the relevance
      of extrinsic factors in the modulation of neurogenesis during critical time
      windows of hippocampal development.

PMID- 21885040
TI  - Exploring and targeting saccades dissociated by saccadic adaptation.
AB  - Saccadic adaptation maintains saccade accuracy and has been studied with
      targeting saccades, i.e. saccades that bring the gaze to a target, with the
      classical intra-saccadic step procedure in which the target systematically jumps
      to a new position during saccade execution. Post-saccadic visual feedback about
      the error between target position and the saccade landing position is crucial to
      establish and maintain adaptation. However, recent research focusing on two
      saccade sequences has shown that exploring saccades, i.e. saccades that explore
      an object, resists this classical intra-saccadic step procedure but can be
      adapted by systematically changing the main parameter used for their coding:
      stimulus size. Here, we adapted an exploring saccade and a targeting saccade in
      two separate experiments, using the appropriate adaptation procedure, and we
      tested whether the adaptation induced on one saccade type transferred to the
      other. We showed that whereas classical targeting saccade adaptation does not
      transfer to exploring saccades, the reciprocal transfer (i.e., from exploring to
      targeting saccades) occurred when targeting saccades aimed for a spatially
      extended stimulus, but not when they aimed for an isolated target. These results
      show that, in addition to position errors, size errors can drive adaptation, and
      confirm that exploring vs. targeting a stimulus leads to two different motor
      planning modes.

PMID- 21885041
TI  - A 16 bp upstream sequence from the rat tyrosine hydroxylase promoter supports
      long-term expression from a neurofilament promoter, in a helper virus-free HSV-1
      vector system.
AB  - Helper virus-free Herpes Simplex Virus vector-mediated gene transfer has
      supported studies on neuronal physiology, and may support specific gene
      therapies. Long-term, neuron-specific expression is required for many of these
      applications. A neurofilament heavy gene (NFH) promoter does not support long
      term expression. We previously developed a promoter that supports long-term
      expression by fusing 6.3 kb of upstream sequences from the rat tyrosine
      hydroxylase (TH) promoter to a NFH promoter, and this promoter has supported
      physiological studies. The TH promoter fragment contains an enhancer, as it has
      activity in both orientations and at a distance from the basal promoter.
      Identifying this enhancer may support further improvements in long-term
      expression. A previous deletion analysis identified two ~100 bp fragments that
      each support long-term expression, and are contained within an ~320 bp fragment
      located ~3 kb from the TH promoter transcription start site. As this analysis
      used overlapping fragments, the two ~100 bp fragments contained 44 or 23 bp of
      unique sequence. Here, we used mutagenesis to identify a short sequence that
      supports long-term expression. We studied a 42 bp sequence, centered on the 23 bp
      unique sequence. Analysis of the wt sequence, and five mutations containing
      clustered changes that spanned the sequence, identified two adjacent mutations
      that do not support long-term expression, which together defined a 16 bp maximum
      essential sequence. This 16 bp sequence contains a putative E2F-1/DP-1
      transcription factor binding site, and this transcription factor is expressed in
      many brain areas.

PMID- 21885042
TI  - Antibody-mediated targeted gene transfer of helper virus-free HSV-1 vectors to
      rat neocortical neurons that contain either NMDA receptor 2B or 2A subunits.
AB  - Because of the numerous types of neurons in the brain, and particularly the
      forebrain, neuron type-specific expression will benefit many potential
      applications of direct gene transfer. The two most promising approaches for
      achieving neuron type-specific expression are targeted gene transfer to a
      specific type of neuron and using a neuron type-specific promoter. We previously
      developed antibody-mediated targeted gene transfer with Herpes Simplex Virus (HSV
      1) vectors by modifying glycoprotein C (gC) to replace the heparin binding
      domain, which mediates the initial binding of HSV-1 particles to many cell types,
      with the Staphylococcus A protein ZZ domain, which binds immunoglobulin (Ig) G.
      We showed that a chimeric gC-ZZ protein is incorporated into vector particles and
      binds IgG. As a proof-of-principle for antibody-mediated targeted gene transfer,
      we isolated complexes of these vector particles and an anti-NMDA NR1 subunit
      antibody, and demonstrated targeted gene transfer to neocortical cells that
      contain NR1 subunits. However, because most forebrain neurons contain NR1, we
      obtained only a modest increase in the specificity of gene transfer, and this
      targeting specificity is of limited utility for physiological experiments. Here,
      we report efficient antibody-mediated targeted gene transfer to NMDA NR2B- or
      NR2A-containing cells in rat postrhinal cortex, and a neuron-specific promoter
      further restricted recombinant expression to neurons. Of note, because NR2A
      containing neurons are relatively rare, these results show that antibody-mediated
      targeted gene transfer with HSV-1 vectors containing neuron type-specific
      promoters can restrict recombinant expression to specific types of forebrain
      neurons of physiological significance.

PMID- 21885043
TI  - The gene encoding cyclooxygenase-2 is regulated by IL-1beta and prostaglandins in
      832/13 rat insulinoma cells.
AB  - The pro-inflammatory cytokine IL-1beta leads to losses in functional beta-cell
      mass in part by inducing the expression of genes that produce soluble mediators
      of inflammation, such as cyclooxygenase-2 (COX2). In the current study, we sought
      to understand what factors control the COX2 gene in response to IL-1beta and how
      prostaglandins downstream of COX2 impact pro-inflammatory gene transcription in
      pancreatic beta-cells. We analyzed COX2 gene expression in response to different
      maneuvers impacting NF-kappaB proteins. Also, we report alterations in the
      expression of COX2, EP-3 and EP-4 receptor genes by PGD(2) and PGE(2). Moreover,
      we examined whether PGD(2) and PGE(2) regulated NF-kappaB and interferon-gamma
      activated sequence (GAS) reporter gene activity. IL-1beta-mediated induction of
      the COX2 gene requires the p65 and p50 subunits of NF-kappaB. In addition, PGD(2)
      and PGE(2) coordinately alter COX2 and EP receptor gene expression patterns and
      potentiate the cytokine-mediated transcriptional activity of promoters containing
      NF-kappaB or GAS response elements.

PMID- 21885044
TI  - [III Consensus Meeting of the Spanish Society of Liver Transplantation. Hepatitis
      C, living-donor liver transplantation, quality of liver grafts and of liver
      transplantation programs].
AB  - The constant updating in the field of liver transplant led to the holding of the
      III Consensus Meeting of the Spanish Liver Transplant Association. Three current
      topics of great clinical interest were debated during this meeting; transplant in
      patients with liver cirrhosis due to hepatitis C, live donor liver transplant and
      the evaluation of the quality of liver grafts. A subject of great interest to
      Liver Transplant Units was also discussed: the assessment of their quality.

PMID- 21885045
TI  - [Indications and results of transanal endoscopic microsurgery in the treatment of
      rectal tumours in a consecutive series of 52 patients].
AB  - INTRODUCTION: The abdominal approach for the treatment of rectal tumours is
      associated with considerable morbidity. Transanal endoscopic microsurgery (TEM)
      is a technical alternative, and less invasive than radical surgery, and thus,
      with a lower associated morbidity. Also, with the correct selection of patients,
      TEM shows similar oncological results to radical surgery. The objective of this
      study is to review our results with TEM and discuss its indications in the
      treatment of rectal tumours. PATIENTS AND METHOD: An observational, retrospective
      study with prospective collection of data conducted from June 2008 to January
      2011. TEM indications were: benign rectal tumours non-resectable using
      colonoscopy; early malignant rectal tumours (T(1)N(0)M(0)) with good prognostic
      factors: neoplastic tumours in more advanced stages in selected patients (high
      surgical risk, refused radical surgery or stoma and palliative care). RESULTS: A
      resection was performed using TEM on 52 patients (35 benign and 17 malignant
      tumours). The mean hospital stay was 4.9 days, with an associated morbidity of
      15.3%. The R(0) resection in adenomas and carcinomas was 97.1% and 88.8%
      respectively. During a follow-up of 15 (3-31) months, one recurrence of an
      adenoma was observed which was re-operated on using TEM. CONCLUSIONS: TEM is a
      safe and effective procedure for the treatment of benign and selected early
      malignant rectal tumours, and is associated with a low morbidity. However, it is
      a therapeutic strategy based on a multidisciplinary team, basically with careful
      selection of patients, a validated technique and a strict follow-up protocol.

PMID- 21885046
TI  - The role of ultrasound in the diagnosis and follow-up of early inflammatory
      arthritis.
AB  - The inflammatory arthritides are a group of chronic, often debilitating disorders
      characterized by synovial inflammation and progressive joint destruction. The
      primary diagnostic aim is to recognize the inflammatory arthritis at an early
      stage, such that therapies may be implemented before irreversible joint
      destruction has occurred. The radiologist now plays a pivotal role both in making
      an accurate and early diagnosis of inflammatory arthritis as well as assessing
      treatment response. This article reviews the current literature and presents our
      approach to the sonographic assessment of early inflammatory arthritis.

PMID- 21885047
TI  - Perineural trigeminal nerve abscess secondary to mucor sinusitis: serial
      diffusion-weighted MRI and literature review.

PMID- 21885048
TI  - Impact of histology on prognosis of patients with early-stage cervical cancer
      treated with radical surgery.
AB  - OBJECTIVE: To examine the effect of carcinoma cell type on tumor characteristics,
      tumor spread, tumor recurrence, and survival of patients with early-stage
      cervical cancer who had radical hysterectomy and pelvic lymphadenectomy. METHOD:
      Data from 499 patients with stage IA to IIA cervical carcinoma who received
      primary surgical treatment from 2003 to 2005 at Chiang Mai University were
      retrospectively reviewed with regard to 3 histologic types; squamous cell
      carcinoma (SCC), adenocarcinoma (AC), and adenosquamous carcinoma (AS). RESULTS:
      Among the 499 patients, 71.1% had SCC, 23.4% had AC, and 5.4% had AS. There was
      no significant difference in stage, tumor size, tumor characteristics, or rate of
      loco-regional spread. A higher proportion of women with SCC needed adjuvant
      radiation (P=0.001). Five-year recurrence-free survival (RFS) and overall
      survival (OS) were comparable among the groups. Among patients with pelvic node
      metastasis, 5-year RFS and OS were significantly lower in those with AC than in
      those with SCC (RFS, 66.1% versus 86.4%, P=0.02; OS, 68.2% versus 88.2%, P=0.05).
      CONCLUSION: There was no difference among SCC, AC, and AS in most tumor
      characteristics, spread, recurrence, and survival in patients with early-stage
      cervical cancer. Among patients with pelvic lymph node metastasis, AC was
      associated with less favorable outcomes than SCC.

PMID- 21885049
TI  - New estimates and trends regarding unsafe abortion mortality.
AB  - BACKGROUND: The 1990-2008 estimates for the maternal mortality associated with
      unsafe abortion require a re-examination. OBJECTIVE: To provide the latest
      estimates of the mortality associated with unsafe abortion and to examine trends
      within the framework of new maternal mortality estimates. SEARCH STRATEGY:
      Extensive search of databases and websites for country- and region-specific data
      on unsafe abortion. SELECTION CRITERIA: Reports, papers, and websites with data
      on unsafe abortion incidence and mortality. DATA COLLECTION AND ANALYSIS: Earlier
      published estimates for the unsafe-abortion-related mortality were recalculated
      by country for 1990, 1997, 2000, and 2003 to harmonize with the new maternal
      mortality estimates. The resulting estimates were aggregated to give subregional,
      regional, and global figures, including those recently estimated for 2008. MAIN
      RESULTS: In 2008, unsafe abortions accounted for an estimated 47000 maternal
      deaths, down from 69000 in 1990. Globally, the unsafe-abortion mortality ratio
      has declined from 50 in 1990 to 30 in 2008. The overall burden of unsafe abortion
      mortality continues to be the highest in Africa. CONCLUSIONS: Important gains
      have been made in reducing maternal deaths attributable to unsafe abortion.
      However, 1 in 8 maternal deaths globally and 1 in 5 maternal deaths in Eastern
      Africa continue to be attributable to unsafe abortion. Averting these preventable
      deaths can contribute to achieving Millennium Development Goal number 5 of
      improving maternal health.

PMID- 21885050
TI  - Alcohol consumption and atherosclerotic burden in the proximal thoracic aorta.
AB  - BACKGROUND: The relationship between alcohol consumption and ischemic stroke or
      aortic atherosclerosis is unclear, but a protective effect of moderate
      consumption on stroke risk has been suggested. We conducted a cross-sectional
      analysis in a population-based sample to evaluate the possible association
      between alcohol consumption and aortic atherosclerotic plaque (AAP), which is
      associated with increased stroke risk. METHODS: As part of the NINDS-funded
      Aortic Plaques and Risk of Ischemic Stroke (APRIS) study, 464 subjects over the
      age of 55 were studied (mean age 69.1 +/- 9.0 with 251 males and 213 females),
      including 255 patients with first ischemic stroke and 209 stroke-free controls.
      Transesophageal echocardiogram was performed for the detection of AAP. Alcohol
      consumption was measured in number of drinks per week during the previous year
      using a standardized questionnaire, and categorized as: (1) none or minimal (<1
      drink per month); (2) light to moderate (between 1 drink per month and 2 drinks
      daily); and (3) heavy (>2 daily). Multivariate conditional logistic regression
      analysis was used to calculate the odds ratios (ORs) and 95% confidence interval
      (CI) for alcohol consumption and AAP after adjustment for the potential
      confounding risk factors (age, sex, hypertension, diabetes, dyslipidemia, and
      cigarette smoking). RESULTS: Overall, AAP was detected in 326 subjects (70.4%),
      and 174 subjects (37.6%) had AAP >= 4 mm, which carry higher stroke risk. No or
      minimal alcohol consumption was present in 241 subjects (53.2%), and 177 subjects
      (39.0%) had light to moderate consumption. Prevalence of light to moderate
      alcohol consumption was significantly lower in stroke patients than in controls
      (35.5% vs. 60.3%, p < 0.001) and in subjects who had AAP compared with those
      without it (41.6% vs. 58.8%, p = 0.008). After adjusting for significant
      predictors of atherosclerosis, alcohol consumption of any degree was inversely
      associated with AAP (OR 0.61; 95% CI 0.37-0.98, p = 0.042). The significance of
      the association was borderline for AAP >= 4 mm (OR 0.64, 95% CI 0.41-1.00, p =
      0.054). In the dose-response analysis, only light to moderate alcohol consumption
      was significantly associated with a lower risk of having any AAP (adjusted OR
      0.45; 95% CI 0.29-0.68, p < 0.001) or AAP >= 4 mm (adjusted OR 0.51; 95% CI 0.34
      0.77, p = 0.001). CONCLUSIONS: Our data indicate that light to moderate alcohol
      consumption is associated with lower atherosclerotic burden in the proximal
      aortic arch. This observation may explain at least in part the lower risk of
      ischemic stroke observed in moderate alcohol consumers.

PMID- 21885051
TI  - Maternal smoking during pregnancy and risk factors for cardiovascular disease in
      adulthood.
AB  - OBJECTIVE: This study was aimed at assessing the effect of maternal smoking
      during pregnancy on metabolic cardiovascular risk factors in early adulthood in a
      Brazilian birth cohort, after controlling for possible confounding variables and
      health behaviors in early adulthood. METHODS: In 1982, the maternity hospitals in
      Pelotas, southern Brazil, were visited and all births were identified. Those
      livebirths whose family lived in the urban area of the city were studied
      prospectively. In 2004-2005, we attempted to follow the whole cohort, the
      subjects were interviewed, examined and blood sample was collected. The following
      outcomes were studied: blood pressure; HDL cholesterol; triglycerides; random
      blood glucose and C-reactive protein. To explore the effect of maternal smoking,
      we adjusted the coefficients for the following possible mediators: perinatal
      factors (low birthweight and preterm births); adult behavioral factors (physical
      activity, dietary pattern, intake of fat and fiber, and tobacco smoking) and
      adult anthropometry (body mass index and waist circumference). RESULTS: In 2004
      2005, we interviewed 4297 subjects, with a follow-up rate of 77.4%. The only
      significant finding in the unadjusted analyses was lower HDL cholesterol among
      females. After adjustment for lifestyle variables in early adulthood, birthweight
      and waist circumference, the difference in HDL levels between offspring of
      smokers and non-smokers reduced from -2.10mg/dL (95% confidence interval: -3.39; 
      0.80) to -1.03 mg/dL (-2.35; 0.30). CONCLUSION: Evidence that maternal smoking
      during pregnancy programs offspring metabolic cardiovascular risk factors are
      scarce, and reported associations are likely due to postnatal exposure to
      lifestyle patterns.

PMID- 21885052
TI  - Effect of pH additive and column temperature on kinetic performance of two
      different sub-2 MUm stationary phases for ultrafast separation of charged
      analytes.
AB  - The performance characteristics of separation were studied for small
      pharmaceuticals and larger charged molecules (peptides) in various mobile phase
      conditions on two 5-cm long narrow bore columns packed with 1.7 MUm core-shell
      and totally porous particles respectively. The effect of temperature and pH
      additives (formic acid, trifluoroacetic acid, ammonium formate, ammonium acetate
      and ammonia) on column efficiency was investigated through a kinetic study based
      upon data obtained under gradient elution conditions. Sample peak capacities were
      calculated and compared in all studied conditions for a sample of ten
      representative peptides having masses ranging from 500 to 2000 Da. The elevation
      of temperature was found to be significantly beneficial. The effect of flow-rate
      on peak shape was also investigated. Ammonium acetate at neutral pH led to the
      best results in terms of both efficiency and peak capacity. It was found that
      column performance was strongly dependent on the type of stationary phase,
      especially in acidic medium.

PMID- 21885053
TI  - Polymer-hybridized liposomes anchored with alkyl grafted poly(asparagine).
AB  - Polymer-hybridized liposomes (PHLs) of saturated lecithin were formed by
      association of poly(asparagines) grafted with alkyl chains (PAsn-g-Cn). The
      thermal, physical, and surface properties of the polymer-hybridized liposomes
      were examined with varying polymer concentration, alkyl chain length (C(8),
      C(12), C(18), C(22)), and degree of substitution (DS) in the polymer. The
      inclusion of the polymer raised the membrane fluidity of liposomes. By the
      incorporation of small amount of polymer, the membrane rigidity of liposomes
      dropped sharply and then increased close to the original level as the polymer
      concentrations increased in the cases of PAsn-g-C(18) and PAsn-g-C(22). Also, the
      membrane rigidity and stability of PHLs increased with alkyl chain length at the
      same polymer concentration. The surface charge of PHL associated with PAsn-g
      C(22) was changed by DS of alkyl chains. The polymer bearing long alkyl chains
      (C(12), C(18), C(22)) formed PHLs well at low polymer concentration and the
      number of disk-shaped polymer-lipid mixed micelles increased with polymer
      concentration. The anchored polymers induced shifts in gel-to-liquid crystal
      transition temperature (Tc) of the vesicles and Tc varied with polymer
      concentration, alkyl chain length, and DS of the polymer.

PMID- 21885054
TI  - Solubilisation of different medium chain esters in zwitterionic surfactant
      solutions--effects on phase behaviour and structure.
AB  - We studied the effect of solubilisation of methyl esters with different chains of
      medium length into the binary surfactant system tetradecyldimethylamine
      oxide/water at constant surfactant concentration of 200 mM. As esters we employed
      valeric, capronic, enanthic, and pelargonic methyl ester, thereby decreasing the
      polarity. Always a phase sequence L(1)-L(alpha)-L(1) is observed with increasing
      ester concentration, where the L(alpha)-phase increases in extent and goes to
      much lower temperatures with increasing chain length of the ester. Viscosity
      measurements show a maximum at intermediate concentrations of additive that is
      independent of the type of ester. From SANS measurements detailed information
      about the structural changes occurring during the rod-to-sphere transition in the
      system of the shortest additive is deduced, which proceeds first through a
      pronounced rod growth. Interestingly, for the different esters an almost constant
      value of the volumic solubilisation capacity is observed, in agreement with the
      relatively constant interfacial tension. For the different esters no effect on
      the radius and the area requirement at the amphiphilic interface is observed at
      the solubilisation boundary. The microemulsions present here are spherical
      aggregates where the ester is partitioned between core and shell. From the SANS
      and interfacial tension data the effective bending constants of the surfactant
      monolayers were deduced and they show that the extension of the L(alpha)-phase is
      directly related to a corresponding increase in the bending constants of the
      surfactant/ester monolayers.

PMID- 21885055
TI  - Perceptions of university instructors toward students who stutter: a quantitative
      and qualitative approach.
AB  - Many research studies have focused on perceptions of stuttering by various groups
      of people. However, there is limited research on the perceptions of university
      instructors toward stuttering and people who stutter. Therefore, this study
      explored the perceptions of university instructors toward stuttering and students
      who stutter, and their beliefs about classroom participation. Participants
      included 328 university instructors across a variety of disciplines at two
      Midwestern universities. Each participant completed a 12-item questionnaire
      regarding perceptions related to stuttering, students who stutter, and classroom
      participation. Of the 328 participants, 212 completed an open-ended question
      about their experiences and concerns of working with students who stutter.
      Results indicated that increased knowledge of stuttering is associated with
      positive attitudes toward students who stutter. Moreover, the participants in
      this study expressed a need for more information about stuttering and ways to
      accommodate students who stutter in the classroom. LEARNING OUTCOMES: After
      reading this article, the reader will be able to: (1) discuss the challenges that
      university instructors face when working with students with disabilities; (2)
      provide a rationale for the need to explore the perceptions of university
      instructors toward students who stutter; (3) describe the major themes of
      university instructors' knowledge of stuttering, and beliefs about classroom
      participation for students who stutter; and (4) discuss the need for
      disseminating more knowledge about stuttering to university instructors.

PMID- 21885056
TI  - The effect of time on word learning: an examination of decay of the memory trace
      and vocal rehearsal in children with and without specific language impairment.
AB  - PURPOSE: The purpose of this study was to measure the effect of time to response
      in a fast-mapping word learning task for children with specific language
      impairment (SLI) and children with typically developing language skills (TD).
      Manipulating time to response allows us to examine decay of the memory trace, the
      use of vocal rehearsal, and their effects on word learning. METHOD: Participants
      included 40 school-age children: half with SLI and half with TD. The children
      were asked to expressively and receptively fast-map 24 novel labels for 24 novel
      animated dinosaurs. They were asked to demonstrate learning either immediately
      after presentation of the novel word or after a 10-second delay. Data were
      collected on the use of vocal rehearsal and for recognition and production
      accuracy. RESULTS: Although the SLI group was less accurate overall, there was no
      evidence of decay of the memory trace. Both groups used vocal rehearsal at
      comparable rates, which did not vary when learning was tested immediately or
      after a delay. Use of vocal rehearsal resulted in better accuracy on the
      recognition task, but only for the TD group. CONCLUSIONS: A delay in time to
      response without interference was not an undue burden for either group. Despite
      the fact that children with SLI used a vocal rehearsal strategy as often as
      unimpaired peers, they did not benefit from the strategy in the same way as their
      peers. Possible explanations for these findings and clinical implications will be
      discussed. LEARNING OUTCOMES: Readers will learn about how time to response
      affects word learning in children with specific language impairment and
      unimpaired peers. They will see how this issue fits into a framework of
      phonological working memory. They will also become acquainted with the effect of
      vocal rehearsal on word learning.

PMID- 21885057
TI  - Dog bite prevention: an assessment of child knowledge.
AB  - OBJECTIVES: To determine what children know about preventing dog bites and to
      identify parental desires for dog bite prevention education. STUDY DESIGN: This
      cross-sectional study sampled 5- to 15-year-olds and their parents/guardians
      presenting to a pediatric emergency department with nonurgent complaints or dog
      bites. The parent/guardian-child pairs completed surveys and knowledge-based
      simulated scenario tests developed on the basis of American Academy of Pediatrics
      and Centers for Disease Control and Prevention dog bite prevention
      recommendations. Regression analyses modeled knowledge test scores and
      probability of passing; a passing score was >=11 of 14 questions. RESULTS: Of 300
      parent/guardian-child pairs, 43% of children failed the knowledge test. Older
      children had higher odds of passing the knowledge test than younger children, as
      did children with white parents vs those with nonwhite parents. No associations
      were found between knowledge scores and other sociodemographic or experiential
      factors. More than 70% of children had never received dog bite prevention
      education, although 88% of parents desired it. CONCLUSIONS: Dog bites are
      preventable injures that disproportionately affect children. Dog bite prevention
      knowledge in our sample was poor, particularly among younger children and
      children with nonwhite parents. Formal dog bite prevention education is warranted
      and welcomed by a majority of parents.

PMID- 21885058
TI  - Health care utilization from prevalent medical conditions in normal-weight,
      overweight, and obese children.
AB  - OBJECTIVE: To explore the commonly recorded diagnoses in overweight and obese
      children presenting to a clinical care setting compared with their normal-weight
      peers. STUDY DESIGN: This was a cross-sectional study linking data from 3361
      fifth grade students from the 2003 Children's Lifestyle and School Performance
      Study with Nova Scotia administrative health data over 6 years. RESULTS:
      Overweight and obese children were more likely to have had a diagnosis of
      internalizing disorders, asthma, other respiratory disorders, obesity, otitis
      media, and chronic adenoid/tonsil disorder. Conversely, normal-weight children
      were more likely to have a diagnosis of conduct disorder or other mental
      diseases. Except for internalizing disorders, overweight and obese children also
      had significantly higher health care costs for these conditions. CONCLUSION:
      Overweight and obese children had higher health care utilization across a range
      of diagnoses, further confirming that health care utilization patterns of
      overweight and obese children differ from those of their normal-weight peers.
      Greater attention to the relationship between more common childhood conditions
      and overweight and obesity is needed, given the greater prevalence in overweight
      and obese children and the fact that some of the more established obesity-related
      conditions occur less frequently, particularly in younger children.

PMID- 21885059
TI  - Treatment of upper airway obstruction and feeding problems in Robin-like
      phenotype.

PMID- 21885060
TI  - Congenital cytomegalovirus infection: prevention is better than treatment.

PMID- 21885062
TI  - Low rates of controller medication initiation and outpatient follow-up after
      emergency department visits for asthma.
AB  - OBJECTIVE: To determine what proportion of patients who are seen in an emergency
      department (ED) for asthma receive inhaled corticosteroids or attend follow-up
      appointments. STUDY DESIGN: This was a retrospective cohort study of 2007-2009
      South Carolina Medicaid data. Enrollees aged 2-18 years who had an ED visit for
      asthma were included. Patients admitted for asthma or with an inhaled
      corticosteroid claim in the 2 months before the month of the ED visit were
      excluded. Covariates were sex, race, age, rural residence, and asthma severity.
      Outcome measures were a prescription for an inhaled corticosteroid filled within
      the 2 months after the ED visit and attendance at a follow-up appointment within
      the 2 months after the ED visit. RESULTS: A total of 3435 patients were included.
      Out of the study cohort, 57% were male, 76% were of a minority race/ethnicity,
      69% lived in an urban areas, 18% had inhaled corticosteroid use, and 12%
      completed follow-up. Multivariate analyses demonstrated that patients with severe
      asthma were more likely to receive an inhaled corticosteroid (OR, 2.9; 95% CI,
      2.3-3.7) and attend a follow-up appointment (OR, 2.0; 95% CI, 1.5-2.6). Patients
      aged 2-6 years and those aged >12 years were less likely to attend follow-up (OR,
      0.71; 95% CI, 0.56-0.90 and OR, 0.62; 95% CI, 0.47-0.83, respectively) (all
      models P < .0001). CONCLUSION: Children with asthma seen in the ED have low rates
      of inhaled corticosteroid use and outpatient follow-up. This indicates a need for
      further interventions to increase the use of inhaled corticosteroids in response
      to ED visits.

PMID- 21885064
TI  - Persistence of fetal hemoglobin expression in an older child with trisomy 13.

PMID- 21885063
TI  - Replication of a genome-wide association study of birth weight in preterm
      neonates.
AB  - OBJECTIVE: To examine associations between rs9883204 in ADCY5 and rs900400 near
      LEKR1 and CCNL1 with birth weight in a preterm population. Both markers were
      associated with birth weight in a term population in a recent genome-wide
      association study of Freathy et al. STUDY DESIGN: A meta-analysis of mother and
      infant samples was performed for associations of rs900400 and rs9883204 with
      birth weight in 393 families from the US, 265 families from Argentina, and 735
      mother-infant pairs from Denmark. Z-scores adjusted for infant sex and
      gestational age were generated for each population separately and regressed on
      allele counts. Association evidence was combined across sites by inverse-variance
      weighted meta-analysis. RESULTS: Each additional C allele of rs900400
      (LEKR1/CCNL1) in infants was marginally associated with a 0.069 SD lower birth
      weight (95% CI, -0.159 to 0.022; P = .068). This result was slightly more
      pronounced after adjusting for smoking (P = .036). No significant associations
      were identified with rs9883204 or in maternal samples. CONCLUSIONS: These results
      indicate the potential importance of this marker on birth weight regardless of
      gestational age.

PMID- 21885065
TI  - Prolonged antibiotic therapy for "culture-negative" sepsis in preterm infants:
      it's time to stop!

PMID- 21885066
TI  - The feasibility and safety of laparoscopic splenectomy for massive splenomegaly:
      a comparative study.
AB  - BACKGROUND: Laparoscopic splenectomy used for massive splenomegaly is still
      controversial. The purpose of our current study was to identify the feasibility
      and safety of laparoscopic splenectomy for massive splenomegaly. METHODS: From
      January 2006 to January 2010, laparoscopic splenectomy was performed on 33
      patients with massive splenomegaly in our hospital, compared with 29 patients who
      received open splenectomy (group 2) and 48 patients with normal-size spleens who
      underwent laparoscopic splenectomy (group 3). Perioperative outcomes of these
      patients were compared. RESULTS: Compared with patients in group 2, the patients
      in group 1 required more operative time, less blood transfusion, and a shorter
      postoperative hospital stay; furthermore, patients in group 1 had less estimated
      blood loss and fewer complications. No statistically significant difference was
      found in the patients' spleen volume and spleen weight. Group 1 had statistically
      significant differences in operative time, estimated blood loss, postoperative
      hospital stay, spleen volume, and spleen weight compared with patients in group
      3. No significant differences were found in the conversion, blood transfusion, or
      complication rate. CONCLUSIONS: Laparoscopic splenectomy is a technically
      feasible and safe procedure for splenomegaly.

PMID- 21885067
TI  - Avoiding sternotomy in repeat coronary artery bypass grafting: Feasibility,
      safety, and mid-term outcome of the transabdominal off-pump technique using the
      right gastroepiploic artery.
AB  - OBJECTIVES: Repeat sternotomy is associated with a substantial risk of
      cardiovascular injury. We evaluated the feasibility and clinical outcome of a
      transabdominal approach without sternotomy and without cardiopulmonary bypass in
      repeat coronary artery bypass grafting, using the right gastroepiploic artery to
      graft vessels of the inferior wall of the heart. METHODS: From July 1999 to
      October 2010, 22 patients presenting with only right coronary artery disease
      underwent reoperation using the transabdominal approach and a skeletonized
      gastroepiploic artery graft. In all patients but 1, a patent graft to the
      anterior wall was present. The mean EuroSCORE was 6.4 +/- 2.5. RESULTS: All
      patients had adequate surgical exposure, and no conversion to sternotomy or the
      use of cardiopulmonary bypass was required. There was no in-hospital mortality.
      Hospital morbidity included pneumothorax in 1 patient and atrial fibrillation in
      2 patients. The median hospital stay was 5 days. Follow-up was complete, and the
      median follow-up time was 6 years. There were 2 late deaths. Four patients
      experienced recurrence of angina, of whom three required percutaneous coronary
      intervention. The estimated freedom from major cardiovascular and cerebrovascular
      events rate was 70.2% at 6 years. Fourteen patients underwent an exercise stress
      test at a median interval of 2 years, with all showing no signs of myocardial
      ischemia. CONCLUSIONS: Transabdominal off-pump coronary artery bypass grafting
      using the right gastroepiploic artery is a safe and effective procedure with low
      in-hospital mortality and morbidity and favorable mid-term outcome. In redo
      operations, this technique excludes the risk of cardiovascular injury.

PMID- 21885068
TI  - Gentamicin-collagen sponge reduces sternal wound complications after heart
      surgery: a controlled, prospectively randomized, double-blind study.
AB  - OBJECTIVE: Prophylactic retrosternal placement of a gentamicin-collagen sponge
      has been the subject of several recent clinical studies and is a matter of
      controversy. The present study is the first controlled, prospective, randomized,
      double-blind, single-center study to investigate the efficacy of a retrosternal
      gentamicin-collagen sponge in reducing sternal wound complications after heart
      surgery. METHODS: From June 2009 to June 2010, 720 consecutive patients who
      underwent median sternotomy were assigned to a control placebo group (collagen
      sponge) or an intervention group (gentamicin-collagen sponge). All patients
      received guideline-compliant perioperative antibiotic prophylaxis. The primary
      end point was the occurrence of deep sternal wound infections within 30 days of
      index surgery (follow-up period). Secondary end points were the occurrence of
      superficial sternal wound infections requiring treatment, as well as further
      clinical parameters, including revision, bleeding volume, and need for
      transfusions during the follow-up period. RESULTS: A total of 720 of 994 patients
      (72.4%) were enrolled (control group: n = 367 vs intervention group: n = 353).
      Risk factors for sternal wound infection and demographic variables were
      comparable in the 2 groups. The incidence of deep sternal wound infections was 13
      of 367 (3.52%) in the control group versus 2 of 353 (0.56%) in the intervention
      group (P = .014; adjusted odds ratio, 0.15; 95% confidence interval, 0.02-0.69).
      The numbers needed to treat relation for all sternal wound infections and deep
      sternal wound infections were 26 and 33, respectively. No statistically
      significant differences were demonstrated concerning secondary end points, such
      as postoperative bleeding and transfusion of red cell units, thrombocytes, and
      fresh-frozen plasma. CONCLUSIONS: Routine prophylactic retrosternal use of a
      gentamicin-collagen sponge in patients undergoing cardiac surgery significantly
      reduces deep sternal wound infections.

PMID- 21885069
TI  - A propensity score-matched comparison of deep versus mild hypothermia during
      thoracoabdominal aortic surgery.
AB  - OBJECTIVE: By using deep hypothermic circulatory arrest and non-deep hypothermic
      circulatory arrest approaches, we examined the impact of distal ischemia time and
      temperature on intra-abdominal reversible adverse outcomes and permanent adverse
      outcomes during descending thoracic aortic and thoracoabdominal aortic aneurysm
      operations. METHODS: A retrospective review of all patients who underwent
      descending thoracic aortic and thoracoabdominal aortic aneurysm repair between
      January 2002 and December 2008 was undertaken, including relevant preoperative,
      intraoperative, and postoperative data, and followed by a propensity score
      matched analysis. Of the total of 262 patients, 240 had data complete enough to
      permit analysis, and 90 were suitable for the propensity-matched study.
      Reversible adverse outcomes included renal failure, liver failure, and temporary
      hemodialysis. Permanent adverse outcomes included paraplegia, permanent
      hemodialysis, and 30-day mortality. RESULTS: Thirty-day mortality was 7.1%
      (17/240). Overall, reversible adverse outcomes developed in 40.8% of patients and
      permanent adverse outcomes developed in 10% of patients. The propensity score
      analysis identified statistically significant decreased odds of developing
      reversible adverse outcomes in patients undergoing deep hypothermic circulatory
      arrest (odds ratio, 0.32; confidence interval, 0.12-0.85). Specifically,
      significantly lower rates of acute renal failure (22% vs 46.4%, P = .03) and
      liver failure (17.8% vs 34.3%, P = .04) were observed in the deep hypothermic
      circulatory arrest group compared with the non-deep hypothermic circulatory
      arrest group. In addition, there were decreased odds of reversible adverse
      outcomes (odds ratio, 0.22; confidence interval, 0.06-0.79) developing in
      patients with a stage II elephant trunk procedure. CONCLUSIONS: During descending
      thoracic aortic and thoracoabdominal aortic aneurysm repairs, the use of deep
      hypothermic circulatory arrest results in improved postoperative adverse outcome
      rates compared with non-deep hypothermic circulatory arrest techniques. The
      development of reversible adverse outcomes is strongly associated with the
      development of permanent adverse outcomes.

PMID- 21885070
TI  - Novel biodegradable polydioxanone stents in a rabbit airway model.
AB  - OBJECTIVE: This study was undertaken to evaluate safety and biocompatibility of a
      novel biodegradable polydioxanone stent in a rabbit tracheal model. Metallic and
      silicone stents represent standard therapeutic approaches for hollow organ
      stenosis, although complications have been reported repeatedly. Biodegradable
      stents could reduce the risks associated with this procedure while still
      achieving the purpose of maintaining lumen patency. METHODS: A commercially
      available polydioxanone suture strand with a long safety record was used to
      manufacture the self-expanding stents. The polydioxanone stents were then
      implanted bronchoscopically and under fluoroscopic guidance into the tracheas of
      white rabbits (N = 25). Periodic clinical examination was performed.
      Histopathologic examination concluded the study for the 5 experimental groups at
      3, 4, 5, 10, and 15 weeks after implantation. RESULTS: There were no unexpected
      deaths and no stent displacements during the study. The animals remained in good
      condition, without stent debris expectoration. Macroscopic examination revealed
      that the tracheal lumen stayed open. Histologic examination showed that tracheal
      damage score was highest 5 weeks after stenting, including in-stent necrosis of
      the epithelium. Stent degradation was complete with no remnants after 10 weeks,
      leaving the trachea completely healed at 15 weeks after implantation.
      CONCLUSIONS: This animal airway model has demonstrated acceptable safety and
      biocompatibility of this novel biodegradable polydioxanone stent. We suggest that
      polydioxanone stenting be used for further clinical studies for cases in which
      complete stent degradation after temporary airway treatment is desirable.

PMID- 21885071
TI  - Impaired cardiac autophagy in patients developing postoperative atrial
      fibrillation.
AB  - OBJECTIVES: Postoperative atrial fibrillation (POAF) is a common complication
      after on-pump heart surgery. Several histologic abnormalities, such as
      interstitial fibrosis and vacuolization, have been described in atrial samples
      from patients developing POAF. This ultrastructural remodeling has been
      associated with the establishment of a proarrhythmic substrate. We studied
      whether atrial autophagy is activated in patients who develop POAF. METHODS: A
      total of 170 patients in sinus rhythm who had undergone elective coronary artery
      bypass grafting were included. Systemic inflammatory markers were measured at
      baseline and 72 hours after surgery. During the procedure, samples of the right
      atrial appendages were obtained for evaluation of remodeling by light and
      electron microscopy. Protein ubiquitination and autophagy-related LC3B processing
      were assessed by Western blot. RESULTS: Of these patients, 22% developed POAF.
      The level of high-sensitivity C-reactive protein, fibrosis, inflammation, myxoid
      degeneration, and ubiquitin-aggregates in the atria did not differ between
      patients with and without POAF. Electron microphotographs of those with POAF
      showed a significant accumulation of autophagic vesicles and lipofuscin deposits.
      Total protein ubiquitination was similar in the patients with and without POAF,
      but LC3B processing was markedly reduced in those with POAF, suggesting a
      selective impairment in autophagic flow. CONCLUSIONS: This study provides novel
      evidence that ultrastructural atrial remodeling characterized by an impaired
      cardiac autophagy is present in patients developing POAF after coronary artery
      bypass surgery.

PMID- 21885072
TI  - The influences of various anthropogenic sources of deterioration on meiobenthos
      (Ostracoda) over the last 100 years in Suo-Nada in the Seto Inland Sea, southwest
      Japan.
AB  - This study focuses on the relationships of water and sediment quality with
      meiobenthos (Ostracoda) over the past 100 years, using a sediment core obtained
      from Suo-Nada in the Seto Inland Sea, Japan. We compared high-resolution
      ostracode results with geochemical and sedimentological data obtained from the
      study core as well as with rich environmental monitoring data that are available.
      R-mode cluster analysis revealed two bioassociations (BC, KA). Until the 1960 s,
      assemblages continued to show high diversity. They changed in approximately 1970,
      when excessive nutrients and organic matter began to be supplied, and most
      species decreased in number. All species of bioassociation BC were dominant again
      by the mid-1990 s; however, those of bioassociation KA containing infaunal
      species did not increase and have been absent or rare since the 1970s because
      organic pollution of sediments has continued to date. This study provided robust
      baseline for ostracode-based long-term environmental monitoring in East Asia.

PMID- 21885073
TI  - Barriers of research utilization from the perspective of nurses in Eastern
      Turkey.
AB  - OBJECTIVES: This study was performed to determine the barriers to the
      implementation of nursing research findings, as perceived by the nurses working
      in the Eastern Anatolian Region. METHODS: The study was performed in the Eastern
      Anatolian Region between April and July 2009. A cross-sectional design was used
      in this study. Thirteen hospitals were randomly selected using a cluster sampling
      technique, encompassing general hospitals in all cities of this region. A total
      of 1094 nurses who agreed to participate in the study were included. The data was
      collected with a questionnaire and "Barriers Scale". Average, percentage
      distribution, and parametric statistical tests were used in data analyses.
      CONCLUSION: According to the Barriers Scale, it was determined that the most
      important impediment perceived by the nurses was "insufficient time on the job to
      implement new ideas". The average point of overall scale was found to be 68.38 +/
      14.66.

PMID- 21885074
TI  - Leishmanicidal effects of piperine, its derivatives, and analogues on Leishmania
      amazonensis.
AB  - Leishmaniasis is a tropical disease caused by protozoan parasites of the genus
      Leishmania which affects 12 million people worldwide. The discovery of drugs for
      the treatment of leishmaniasis is a pressing concern in global health programs.
      The aim of this study aim was to evaluate the leishmanicidal effect of piperine
      and its derivatives/analogues on Leishmania amazonensis. Our results showed that
      piperine and phenylamide are active against promastigotes and amastigotes in
      infected macrophages. Both drugs induced mitochondrial swelling, loose
      kinetoplast DNA, and led to loss of mitochondrial membrane potential. The
      promastigote cell cycle was also affected with an increase in the G1 phase cells
      and a decrease in the S-phase cells, respectively, after piperine and phenylamide
      treatment. Lipid analysis of promastigotes showed that piperine reduced
      triglyceride, diacylglycerol, and monoacylglycerol contents, whereas phenylamide
      only reduced diacylglycerol levels. Both drugs were deemed non toxic to
      macrophages at 50 MUM as assessed by XTT (sodium 2,3,-bis(2-methoxy-4-nitro-5
      sulfophenyl)-5-[(phenylamino)-carbonyl]-2H-tetrazolium inner salt), Trypan blue
      exclusion, and phagocytosis assays, whereas low toxicity was noted at
      concentrations higher than 150 MUM. None of the drugs induced nitric oxide (NO)
      production. By contrast, piperine reduced NO production in activated macrophages.
      The isobologram analysis showed that piperine and phenylamide acted
      synergistically on the parasites suggesting that they affect different target
      mechanisms. These results indicate that piperine and its phenylamide analogue are
      candidates for development of drugs for cutaneous leishmaniasis treatment.

PMID- 21885075
TI  - Immunotherapy in human glioblastoma.
AB  - Glioblastoma patients spontaneously develop anti-tumour immune responses.
      However, the tumour itself develops several mechanisms that allow the tumor to
      escape the immune system. Clinical trials using infusion of activated autologous
      immune cells, or active immunotherapy with tumor antigens and dendritic cells
      have successfully induced anti-tumour immunity and some radiological responses.
      More recently, approaches targeting the mechanisms of tolerance have shown
      promising data in melanoma, and are currently under investigations in gliomas.
      However, large randomised trials are still needed to prove the usefulness of
      cancer vaccines in brain tumors.

PMID- 21885076
TI  - Metabolism of glioma and IDH1/IDH2 mutations.
AB  - Many known oncogenic signaling pathways involved in gliomagenesis have strong
      consequences on tumor cell metabolism, and promote the switch from oxidative
      phosphorylation to aerobic glycolysis, for ATP generation. However, the interest
      on metabolism has been recently renewed by the discovery of recurrent mutation of
      IDH1 genes by systematic sequencing of a glioblastoma series. IDH1 encodes the
      cytoplasmic NADP dependent isocitrate dehydrogenase1 that catalyzes the oxidative
      decarboxylation of isocitrate into alpha-ketoglutarate. IDH1, more rarely IDH2,
      is mutated in 40% of gliomas (roughly 70% of low-grade gliomas, 50% of grade III,
      and 5 to 10% of primary glioblastomas). IDH1/IDH2 mutations are associated with
      genomic profile, being present in nearly all the 1p19q codeleted gliomas, and
      virtually absent in gliomas with EGFR amplification. It is a strong and
      independent predictor of survival, whatever grade considered. IDH1/IDH2 mutation
      results in a new enzymatic activity transforming alpha-ketoglutarate into 2
      hydroxyglutarate (2-HG). The oncometabolite 2-HG accumulates in the cell and acts
      as a competitive inhibitor of many alpha-ketoglutarate dependent cellular
      reactions. The cellular consequences of this mutation offer potential targets for
      the development of novel therapeutics.

PMID- 21885077
TI  - Efficacy of single and double doses of albendazole and mebendazole alone and in
      combination in the treatment of Trichuris trichiura in school-age children in
      Uganda.
AB  - A randomised clinical trial was conducted in Kabale District, southwestern
      Uganda, to compare the efficacies of single and double doses of a combination of
      400mg albendazole (ALB) and 500mg mebendazole (MBZ) with those of single and
      double doses of each drug given alone in the treatment of Trichuris trichiura.
      Infected pupils (n=611) were randomised to six treatment groups. Three groups
      received either a single dose of ALB, MBZ or the combination (ALB+MBZ). The other
      three groups received either a double dose of ALB (ALB/ALB), MBZ (MBZ/MBZ) or the
      combination (ALB+MBZ/ALB+MBZ). All double doses were given 8h apart. Children
      were followed-up weekly for 1 month. Cure rates were significantly higher using
      double doses compared with single doses (irrespective of drug; z=-4.02, P<0.0005)
      as well as using the drug combination compared with single drugs (irrespective of
      doses; z=-7.64, P<0.0005). Cure rates measured at Day 7 were significantly higher
      than on Days 14 and 21 after treatment (Day 14, z=9.90, P<0.0005; Day 21, z=7.36,
      P<0.0005). Geometric mean (GM) intensities of positives were significantly lower
      on Day 7 compared with all other subsequent days (P<0.00005), and on Day 28 GM
      intensities reached pre-treatment levels (P=0.096). Whilst there was no
      difference in egg excretion between single and double doses of the same drug or
      drug combination (F((df)(1))=0.28, P=0.60), the combination treatment resulted in
      lower egg excretion than use of single drugs (F((df)(2))=50.90, P<0.00005). All
      the tested regimens of ALB and MBZ had low cure rates against T. trichiura in
      Uganda, but both combination treatments showed satisfactory egg reduction rates 3
      weeks after treatment.

PMID- 21885078
TI  - Oscillations of a statistical scattering in the Rayleigh limit and the Rayleigh
      law violation.
AB  - Oscillations of the Rayleigh wave statistical scattering in the Rayleigh limit
      are theoretically found. These oscillations are violation of the Rayleigh law of
      scattering. They are caused by the diffraction of a new form - the extraordinary
      scattering in the Rayleigh limit, which leads to the different frequency
      dependencies of the scattering coefficient and thus violates the Rayleigh law of
      scattering. The fundamental physical conception that a wave does not sense the
      structure of an irregularity in a long-wavelength scattering, when the wavelength
      is much greater than the character size of the irregularity, i.e. in the Rayleigh
      limit, is violated as well.

PMID- 21885080
TI  - QMRAspot: a tool for Quantitative Microbial Risk Assessment from surface water to
      potable water.
AB  - In the Netherlands, a health based target for microbially safe drinking water is
      set at less than one infection per 10,000 persons per year. For the assessment of
      the microbial safety of drinking water, Dutch drinking water suppliers must
      conduct a Quantitative Microbial Risk Assessment (QMRA) at least every three
      years for the so-called index pathogens enterovirus, Campylobacter,
      Cryptosporidium and Giardia. In order to collect raw data in the proper format
      and to automate the process of QMRA, an interactive user-friendly computational
      tool, QMRAspot, was developed to analyze and conduct QMRA for drinking water
      produced from surface water. This paper gives a description of the raw data
      requirements for QMRA as well as a functional description of the tool. No
      extensive prior knowledge about QMRA modeling is required by the user, because
      QMRAspot provides guidance to the user on the quantity, type and format of raw
      data and performs a complete analysis of the raw data to yield a risk outcome for
      drinking water consumption that can be compared with other production locations,
      a legislative standard or an acceptable health based target. The uniform approach
      promotes proper collection and usage of raw data and, warrants quality of the
      risk assessment as well as enhances efficiency, i.e., less time is required.
      QMRAspot may facilitate QMRA for drinking water suppliers worldwide. The tool
      aids policy makers and other involved parties in formulating mitigation
      strategies, and prioritization and evaluation of effective preventive measures as
      integral part of water safety plans.

PMID- 21885079
TI  - Parainfluenza virus 5-based vaccine vectors expressing vaccinia virus (VACV)
      antigens provide long-term protection in mice from lethal intranasal VACV
      challenge.
AB  - To test the potential for parainfluenza virus 5 (PIV5)-based vectors to provide
      protection from vaccinia virus (VACV) infection, PIV5 was engineered to express
      secreted VACV L1R and B5R proteins, two important antigens for neutralization of
      intracellular mature (IMV) and extracellular enveloped (EEV) virions,
      respectively. Protection of mice from lethal intranasal VACV challenge required
      intranasal immunization with PIV5-L1R/B5R in a prime-boost protocol, and
      correlated with low VACV-induced pathology in the respiratory tract and anti-VACV
      neutralizing antibody. Mice immunized with PIV5-L1R/B5R showed some disease
      symptoms following VACV challenge such as loss of weight and hunching, but these
      symptoms were delayed and less severe than with unimmunized control mice. While
      immunization with PIV5 expressing B5R alone conferred at least some protection,
      the most effective immunization included the PIV5 vector expressing L1R alone or
      in combination with PIV5-B5R. PIV5-L1R/B5R vectors elicited protection from VACV
      challenge even when CD8+ cells were depleted, but not in the case of mice that
      were defective in B cell production. Mice were protected from VACV challenge out
      to at least 1.5 years after immunization with PIV5-L1R/B5R vectors, and showed
      significant levels of anti-VACV neutralizing antibodies. These results
      demonstrate the potential for PIV5-based vectors to provide long lasting
      protection against complex human respiratory pathogens such as VACV, but also
      highlight the need to understand mechanisms for the generation of strong immune
      responses against poorly immunogenic viral proteins.

PMID- 21885081
TI  - Electrochemical sulfide oxidation from domestic wastewater using mixed metal
      coated titanium electrodes.
AB  - Hydrogen sulfide generation is a major issue in sewer management. A novel method
      based on electrochemical sulfide oxidation was recently shown to be highly
      effective for sulfide removal from synthetic and real sewage. Here, we compare
      the performance of five different mixed metal oxide (MMO) coated titanium
      electrode materials for the electrochemical removal of sulfide from domestic
      wastewater. All electrode materials performed similarly in terms of sulfide
      removal, removing 78+/-5%, 77+/-1%, 85+/-4%, 84+/-1%, and 83+/-2% at a current
      density of 10 mA/cm(2) using Ta/Ir, Ru/Ir, Pt/Ir, SnO(2) and PbO(2),
      respectively. Elevated chloride concentrations, often observed in coastal areas,
      did not entail any significant difference in performance. Independent of the
      electrode material used, sulfide oxidation by in situ generated oxygen was the
      predominant reaction mechanism. Passivation of the electrode surface by
      deposition of elemental sulfur did not occur. However, scaling was observed in
      the cathode compartment. This study shows that all the MMO coated titanium
      electrode materials studied are suitable anodic materials for sulfide removal
      from wastewater. Ta/Ir and Pt/Ir coated titanium electrodes seem the most
      suitable electrodes since they possess the lowest overpotential for oxygen
      evolution, are stable at low chloride concentration and are already used in full
      scale applications.

PMID- 21885082
TI  - Nitrate reduction in a simulated free-water surface wetland system.
AB  - The feasibility of using a constructed wetland for treatment of nitrate
      contaminated groundwater resulting from the land application of biosolids was
      investigated for a site in the southeastern United States. Biosolids degradation
      led to the release of ammonia, which upon oxidation resulted in nitrate
      concentrations in the upper aquifer in the range of 65-400 mg N/L. A laboratory
      scale system was constructed in support of a pilot-scale project to investigate
      the effect of temperature, hydraulic retention time (HRT) and nitrate and carbon
      loading on denitrification using soil and groundwater from the biosolids
      application site. The maximum specific reduction rates (MSRR), measured in batch
      assays conducted with an open to the atmosphere reactor at four initial nitrate
      concentrations from 70 to 400 mg N/L, showed that the nitrate reduction rate was
      not affected by the initial nitrate concentration. The MSRR values at 22  degrees
      C for nitrate and nitrite were 1.2 +/- 0.2 and 0.7 +/- 0.1 mg N/mg VSS(COD)-day,
      respectively. MSRR values were also measured at 5, 10, 15 and 22  degrees C and
      the temperature coefficient for nitrate reduction was estimated at 1.13. Based on
      the performance of laboratory-scale continuous-flow reactors and model
      simulations, wetland performance can be maintained at high nitrogen removal
      efficiency (>90%) with an HRT of 3 days or higher and at temperature values as
      low as 5  degrees C, as long as there is sufficient biodegradable carbon
      available to achieve complete denitrification. The results of this study show
      that based on the climate in the southeastern United States, a constructed
      wetland can be used for the treatment of nitrate-contaminated groundwater to low,
      acceptable nitrate levels.

PMID- 21885083
TI  - Speciation of trace inorganic contaminants in corrosion scales and deposits
      formed in drinking water distribution systems.
AB  - Sequential extractions utilizing the modified Tessier scheme (Krishnamurti et
      al., 1995) and measurements of soluble and particulate metal released from
      suspended solids were used in this study to determine the speciation and mobility
      of inorganic contaminants (As, Cr, V, U, Cd, Ni, and Mn) found in corrosion
      scales and particles mobilized during hydraulic flushing events. Arsenic,
      chromium and vanadium are primarily associated with the mobilization-resistant
      fraction that is resistant to all eluents used in this study and also bound in
      highly stable crystalline iron oxides. Very low concentrations of these elements
      were released in resuspension experiments. X-ray absorbance measurements
      demonstrated that arsenic in the sample with the highest As concentration was
      dominated by As(V) bound by iron oxides. Significant fractions of uranium and
      cadmium were associated with carbonate solids. Nickel and manganese were
      determined to be more mobile and significantly associated with organic fractions.
      This may indicate that biofilms and natural organic matter in the drinking water
      distributions systems play an important role in the accumulation and release of
      these inorganic contaminants.

PMID- 21885084
TI  - GIS-based source identification and apportionment of diffuse water pollution:
      perfluorinated compound pollution in the Tokyo Bay basin.
AB  - To efficiently reduce perfluorinated compound (PFC) pollution, it is important to
      have an understanding of PFC sources and their contribution to the pollution. In
      this study, source identification of diffuse water pollution by PFCs was
      conducted using a GIS-based approach. Major components of the source
      identification were collection of the monitoring data and preparation of the
      corresponding geographic information that was extracted from a constructed GIS
      database. The spatially distributed pollution factors were then explored by
      multiple linear regression analysis, after which they were visually expressed
      using GIS. Among the 35 PFC homologues measured in a survey of the Tokyo Bay
      basin, 18 homologues were analyzed. Pollution by perfluorooctane sulfonate (PFOS)
      was explained well by the percentage of arterial traffic area in the basin, and
      the 84% variance of the measured PFOS concentration was explained by two
      geographic variables, arterial traffic area and population. Source apportionment
      between point and nonpoint sources was conducted based on the results of the
      analysis. The contribution of PFOS from nonpoint sources was comparable to that
      from point sources in several major rivers flowing into Tokyo Bay. Source
      identification and apportionment using the GIS-based approach was shown to be
      effective, especially for ubiquitous types of pollution, such as PFC pollution.

PMID- 21885085
TI  - Polybrominated diphenyl ethers in sewage sludge from Shanghai, China: possible
      ecological risk applied to agricultural land.
AB  - Ideally, agricultural use is a treatment for the sewage sludge generated from
      municipal wastewater. However, this treatment probably causes ecological risks
      due to the occurrence of organic contaminants in sludge, which has attracted
      rising concerns recently. To assess the possible ecological risk, in this study,
      sewage sludge samples were collected from 28 wastewater treatment plants (WWTPs)
      in Shanghai, China for exploring the level and profile of polybrominated diphenyl
      ethers (PBDEs). The mean concentration of Sigma18PBDE (sum of all target analytes
      except for BDE-209) was at the low end of global range. However, we found the
      highest reported BDE-209 levels (34,900 ng g(-1) dw) in sewage sludge/biosoilds
      to date. The annual mass loadings of penta-BDE, octa-BDE, and deca-BDE were 3.6,
      0.6, and 763 kg through sludge, respectively. Following sludge application in
      agricultural land, the concentrations of penta-BDE, octa-BDE, and deca-BDE in
      soil were 0.19, 0.03, and 39.5 ng g(-1), respectively. Preliminary results
      indicate that the ecological risk of soil in organisms exposed to PBDEs was
      relatively low. Nevertheless, further studies are needed to explore the fate of
      PBDEs in sewage sludge due to no restriction on the usage and production of PBDEs
      products in China currently.

PMID- 21885086
TI  - Atmospheric fate of non-volatile and ionizable compounds.
AB  - A modified version of the Multimedia Activity Model for Ionics MAMI, including
      two-layered atmosphere, air-water interface partitioning, intermittent rainfall
      and variable cloud coverage was developed to simulate the atmospheric fate of ten
      low volatility or ionizable organic chemicals. Probabilistic simulations
      describing the uncertainty of substance and environmental input properties were
      run to evaluate the impact of atmospheric parameters, ionization and air-water
      (or air-ice) interface enrichment. The rate of degradation and the concentration
      of OH radicals, the duration of dry and wet periods, and the parameters
      describing air-water partitioning (K(AW) and temperature) and ionization (pK(a)
      and pH) are the key parameters determining the potential for long range
      transport. Wet deposition is an important removal process, but its efficiency is
      limited, primarily by the duration of the dry period between precipitation
      events. Given the underlying model assumptions, the presence of clouds
      contributes to the higher persistence in the troposphere because of the capacity
      of cloud water to accumulate and transport non-volatile (e.g. 2,4-D) and surface
      active chemicals (e.g. PFOA). This limits the efficiency of wet deposition from
      the troposphere enhancing long-range transport.

PMID- 21885087
TI  - Cadmium- and calcium-mediated toxicity in rainbow trout (Oncorhynchus mykiss) in
      vivo: interactions on fitness and mitochondrial endpoints.
AB  - Rainbow trout were exposed to sublethal waterborne Cd (5 and 10 MUg L(-1)) and
      dietary Ca (60 mg g(-1)), individually and in combination, for 30 d to elucidate
      the interactive effects and evaluate the toxicological significance of
      mitochondrial responses to these cations in vivo. Indices of fish condition and
      mortality were measured and livers, centers of metabolic homeostasis, were
      harvested to assess mitochondrial function and cation accumulation. All indices
      of condition assessed (body weight, hepatosomatic index and condition factor)
      were reduced in all the treatment groups. Mortality occurred in the Cd-exposed
      groups with dietary Ca partly protecting against and enhancing it in the lower
      and higher Cd exposure, respectively. State 3 mitochondrial respiration was
      inhibited by 30%, 35% and 40% in livers of fish exposed to Ca, Cd and Cd+Ca,
      respectively, suggesting reduced ATP turnover and/or impaired substrate
      oxidation. While the phosphorylation efficiency was unaffected, state 4 and state
      4+ (+ oligomycin) respirations were inhibited by all the exposures. Mitochondrial
      coupling was reduced and transiently restored denoting partially effective
      compensatory mechanisms to counteract Cd/Ca toxicity. The respiratory dysfunction
      was associated with accumulation of both Cd and Ca in the mitochondria. Although
      fish that survived acute effects of Cd and Ca exposure apparently made
      adjustments to energy generation such that liver mitochondria functioned more
      efficiently albeit at reduced capacity, reduced fitness was persistent possibly
      due to increased demands for maintenance and defense against toxicity. Overall,
      interactions between Cd and Ca on condition indices and mitochondrial responses
      were competitive or cooperative depending on exposure concentrations and
      duration.

PMID- 21885088
TI  - Characterisation and fingerprinting of PCBs in flue gas and ash from waste
      incineration and in technical mixtures.
AB  - Congener patterns of mono- to deca-chlorinated biphenyls (PC1-10B) were evaluated
      in (a) waste incineration flue gases collected in the post-combustion zone of a
      laboratory-scale fluidized-bed reactor, (b) ashes from two different MSW
      incineration plants, and (c) published data of eight Aroclor formulations. The
      congener patterns of the flue gases, ashes, and Aroclor mixtures clearly differed
      from each other, likely reflecting differences in formation pathways. The flue
      gas congener patterns were largely dominated by the least chlorinated congeners,
      whereas the ashes displayed more evenly distributed patterns. The most abundant
      congeners indicated a preference for 3,3',4,4'-oriented substitution, which may
      be related to de novo-type formation involving perylene. Principal component
      analysis confirmed that congener patterns differed among the three matrices and
      also distinguished flue gases collected at 200  degrees C from those collected at
      300  degrees C and 450  degrees C. This distinction could be partly explained by
      the degree of chlorination, although the substitution status of the ortho
      position, and substitution in the 3,3',4,4'-positions also seemed to be
      influential. Injecting biphenyl into the post-combustion zone of the reactor did
      not alter the patterns, indicating that availability of the backbone structure is
      not a limiting factor for PCB formation.

PMID- 21885089
TI  - Evaluation of the fish short term reproduction assay for detecting endocrine
      disrupters.
AB  - In a fish testing strategy, positive results of the fish short term reproduction
      assay (FSTR), often trigger a definitive test like the fish sexual development
      test (FSDT) or the fish full life cycle test (FFLC), entailing ethical and
      economic problems. This study analysed 137 studies encompassing 35 chemicals with
      different modes of actions (MOAs). Variability is quantified for MOA endpoints
      vitellogenin (VTG) and secondary sex characteristics (SSCs) as well as for apical
      endpoints. Two MOA endpoints could indicate estrogenic, anti-estrogenic,
      androgenic, anti-androgenic and steroidogenesis activities. Great variability,
      however, has been observed for chemicals with anti-androgenic and steroidogenesis
      activities, suggesting that TG229/230 may not be sensitive enough to detect these
      types of chemicals and may produce false negatives. Changes in apical endpoints
      like fecundity are not limited to endocrine disrupting chemicals (EDCs). Non-EDCs
      could induce the similar effects on these apical endpoints. If elucidating MOA is
      needed, targeted in vitro MOA tests are suggested. Positive in vitro MOA results
      trigger a definitive test, which could be used for confirmation of the MOA in
      vivo and for deriving a no observed effect concentration (NOEC). Based on
      positive MOA results of TG229, a definitive test such as the FSDT or the FFLC is
      still needed, because the current TG229 has limitation on the derivation of a
      NOEC. An extended TG229 with more power to detect reproduction effects, as
      recently proposed in the OECD test guideline program, would improve the
      possibility to derive a NOEC and increase its usefulness in risk assessment.

PMID- 21885090
TI  - Stream water hydrochemistry as an indicator of carbon flow paths in Finnish
      peatland catchments during a spring snowmelt event.
AB  - Extreme hydrological events are known to contribute significantly to total annual
      carbon export, the largest of which in Arctic and boreal catchments is spring
      snowmelt. Whilst previous work has quantified the export of carbon during
      snowmelt, the source of the carbon remains unclear. Here we use cation
      hydrochemistry to trace the primary flowpaths which govern the export of carbon
      during the snowmelt period; specifically we aim to examine the importance of
      snowpack meltwater to catchment carbon export. The study was carried out in two
      forested peatland (drained and undrained) catchments in Eastern Finland. Both
      catchments were characterised by base-poor stream water chemistry, with cation
      concentrations generally decreasing in response to increasing discharge.
      Streamflow during the snowmelt period was best described as a mixture of three
      sources: pre-event water, snowpack meltwater and a third dilute component we
      attribute to the upper snow layer which was chemically similar to recent
      precipitation. Over the study period, pre-event water contributed 32% and 43% of
      the total stream runoff in Valipuro (undrained) and Suopuro (drained),
      respectively. The results also suggest a greater near-surface throughflow
      component in Suopuro, the drained catchment, prior to snowmelt. CO(2) and DOC
      concentrations correlated positively with cation concentrations in both
      catchments indicating a common, peat/groundwater flowpath. CH(4) concentrations
      were significantly higher in the drained catchment and appeared to be transported
      in near-surface throughflow. Meltwater from the snowpack represented an important
      source of stream water CO(2) in both catchments, contributing up to 49% of total
      downstream CO(2) export during the study period. We conclude that the snowpack
      represents a potentially important, and often overlooked, transient carbon store
      in boreal snow-covered catchments.

PMID- 21885091
TI  - Biogeochemical cycling of arsenic in coastal salinized aquifers: Evidence from
      sulfur isotope study.
AB  - Arsenic (As) contamination of groundwater, accompanied by critical salinization,
      occurs in the southwestern coastal area of Taiwan. Statistical analyses and
      geochemical calculations indicate that a possible source of aqueous arsenic is
      the reductive dissolution of As-bearing iron oxyhydroxides. There are few reports
      of the influence of sulfate-sulfide redox cycling on arsenic mobility in brackish
      groundwater. We evaluated the contribution of sulfate reduction and sulfide re
      oxidation on As enrichment using delta(34)S([SO(4)]) and delta(18)O([SO(4)])
      sulfur isotopic analyses of groundwater. Fifty-three groundwater samples were
      divided into groups of high-As content and salinized (Type A), low-As and non
      salinized (Type B), and high-As and non-salinized (Type C) groundwaters, based on
      hydro-geochemical analysis. The relatively high enrichment of (34)S([SO(4)]) and
      (18)O([SO(4)]) present in Type A, caused by microbial-mediated reduction of
      sulfate, and high (18)O enrichment factor (epsilon([SO(4)-H(2)O])), suggests that
      sulfur disproportionation is an important process during the reductive
      dissolution of As-containing iron oxyhydroxides. Limited co-precipitation of ion
      sulfide increased the rate of As liberation under anaerobic conditions. In
      contrast to this, Type B and Type C groundwater samples showed high
      delta(18)O([SO(4)]) and low delta(34)S([SO(4)]) values under mildly reducing
      conditions. Base on (18)O mass balance calculations, the oxide sources of sulfate
      are from infiltrated atmospheric O(2), caused by additional recharge of dissolved
      oxygen and sulfide re-oxidation. The anthropogenic influence of extensive pumping
      also promotes atmospheric oxygen entry into aquifers, altering redox conditions,
      and increasing the rate of As release into groundwater.

PMID- 21885092
TI  - The Nile monitor (Varanus niloticus; Squamata: Varanidae) as a sentinel species
      for lead and cadmium contamination in sub-Saharan wetlands.
AB  - Wetland pollution is a matter of concern in sub-Saharan Africa. Though regularly
      exploited, the Nile monitor (Varanus niloticus), a large amphibious lizard, is
      not threatened. This work aims at assessing the value of this varanid as a
      sentinel species in surveys of environmental contamination by metals. Lead and
      cadmium quantifications were performed by graphite furnace-atomic absorption
      spectrophotometry in bone, intestine, kidney, liver and muscle in 71 monitors
      from three unevenly polluted sites in Mali and Niger, plus a reference site. The
      effects of sex, size and fat reserves as well as factors related to the sampling
      strategy (tissue sampled, sampling site) were studied with a mixed linear model.
      Metal contamination is moderate at the four sites but clear differences
      nevertheless occur. Lead levels are generally maximal in bone, with a gender
      independent median value 320ng.g(-1). Median cadmium concentrations never exceed
      70.2ng.g(-1) in females (kidney) and 57.5ng.g(-1) in males (intestine). Such
      levels should have no detrimental effects on the monitors. Lead and cadmium
      levels in muscles are generally below 200 and 20ng.g(-1), respectively, and
      should provoke no health hazard to occasional consumers of monitor meat. Metal
      organotropisms are consistent with those observed in other studies about
      Squamates: for lead: bone>[kidney, intestine, liver]>muscle in males and [bone,
      kidney]>[intestine, liver]>muscle in females; for cadmium: [liver, intestine,
      kidney]>[bone, muscle] for both genders. Females are more contaminated,
      especially in their kidneys. In this tissue, median values in ng.g(-1) are 129.7
      and 344.0 for lead and 43.0 and 70.2 for cadmium, for males and females,
      respectively. Nile monitors can reveal subtle differences in local pollution by
      metals; moreover, the spatial resolution of the pollution indication that they
      give seems to be very sharp. The practical relevance of this new tool is thus
      validated.

PMID- 21885093
TI  - The risk of occurrence of venous thrombosis: focus on protein Z.
AB  - Protein Z (PZ) is a vitamin K-dependent factor identified in human plasma in 1984
      characterized by an homology with other vitamin K-dependent factors. PZ acts as
      the cofactor of the PZ dependent inhibitor (ZPI), in the inhibition of activated
      factor X bound on phospholipid surface. In humans, PZ is characterized by an
      unusual wide distribution in plasma partly explained by a genetic control.
      Several PZ gene polymorphisms influencing plasma concentration have been
      described. In mice, the disruption of PZ gene is asymptomatic, but in association
      with homozygous FV Leiden produced a severe prothrombotic phenotype. This review
      analyzes the results obtained from different studies so far published in order to
      understand whether PZ deficiency could be considered as a risk factor for venous
      thrombosis. The roles of PZ plasma level and PZ gene polymorphisms remain debated
      with conflicting results. Many of these studies reported low PZ levels in
      association with an increased risk of venous thrombosis. On the other side, some
      studies did not observe an association between low levels of PZ and thrombotic
      events. A relationship between PZ deficiency and pregnancy complications was also
      described but not confirmed by all studies. These discrepancies can be explained
      by the heterogeneity of populations chosen as control, by the PZ interindividual
      variability and by the small size of the cohorts in mainly retrospective studies.
      Large prospective studies remain to be done to investigate its possible role in
      thrombosis.

PMID- 21885094
TI  - Single institution experience comparing double-barreled wet colostomy to ileal
      conduit for urinary and fecal diversion.
AB  - OBJECTIVE: To compare outcomes and feasibility of double-barreled wet colostomy
      and ileal conduit (IC) in patients undergoing total pelvic exenteration (TPE).
      METHODS: Between 2004 and 2010, 54 patients underwent TPE for pelvic
      malignancies. Of those patients, 53 had complete records available for analysis.
      Two groups were identified based on the technique used for urinary diversion,
      either by way of an IC or a double-barreled wet colostomy (DBWC). Demographics,
      comorbidities, complications, length of stay, operative times, morbidity, and
      mortality were compared between the 2 groups. RESULTS: Forty-three patients (81%)
      underwent a DBWC and ten patients (19%) underwent an IC. The 2 groups were
      similar in terms of age, gender, and comorbidities. Eighteen patients underwent
      an R0 resection (39%) and twenty-eight (61%) patients had a non-R0 resection.
      Seven patients (13%) had a complete response to therapy with no evidence of
      malignancy. A majority of the patients (68%) undergoing TPE had colorectal
      histology. Thirty-day morbidity directly related to complications of urinary or
      fecal diversion was 78% in the DBWC group and 58% in the IC group. There was no
      perioperative mortality in either group. CONCLUSION: DBWC is a safe and feasible
      alternative to the traditional IC for urinary diversion. This technique is easy
      to learn and is associated with similar operative times, length of stay,
      morbidity, and mortality compared with IC.

PMID- 21885095
TI  - The eliciting dose of peanut in double-blind, placebo-controlled food challenges
      decreases with increasing age and specific IgE level in children and young
      adults.
AB  - BACKGROUND: Several risk factors for severe anaphylactic reactions to food in
      daily life are known. However, to date, it is not possible to predict the
      severity of allergic reactions to food in the individual patient with accuracy.
      Some studies show that a history of severe reactions is associated with a lower
      eliciting dose in double-blind, placebo-controlled food challenges (DBPCFCs).
      Therefore, in this study, the eliciting dose was used as a measure of clinical
      sensitivity. OBJECTIVES: To study whether risk factors for severe allergic
      reactions to food in daily life such as age, degree of sensitization, and
      coexistent atopic disease influence the eliciting dose in DBPCFCs in children
      allergic to peanut. METHODS: Data from children who had clinical reactions to
      peanut during DBPCFCs at the University Medical Center Groningen (2001-2009) were
      analyzed. A Cox regression model was used to analyze the association of the
      determinants with the eliciting dose. RESULTS: One hundred twenty-six positive
      DBPCFCs with peanut were analyzed. Age older than 10 years, a specific IgE level
      above the lowest tertile (>= 5.6 kU/L), and the absence of atopic dermatitis were
      associated with reactions to lower doses: respective hazard ratios 1.89 (95% CI,
      1.28-2.81; P = .001), 2.03 (95% CI, 1.37-3.00; P < .0001), and 0.45 (95% CI, 0.29
      0.71; P = .001) present versus absent. No significant associations with the
      eliciting dose were found for sex, the presence of asthma and rhinitis, and the
      severity of food reactions by history. CONCLUSIONS: Using the eliciting dose as a
      measure of clinical sensitivity, greater clinical sensitivity in DBPCFCs to
      peanut was found to be associated with increasing age, higher specific IgE level,
      and the absence of atopic dermatitis. This finding may explain why adolescents
      experience severe allergic reactions in daily life to peanut more often than do
      younger children.

PMID- 21885096
TI  - Re-invigorating Japan's commitment to global health: challenges and
      opportunities.
AB  - Over the past 50 years, Japan has successfully developed and maintained an
      increasingly equitable system of universal health coverage in addition to
      achieving the world's highest life expectancy and one of the lowest infant
      mortality rates. Against this backdrop, Japan is potentially in a position to
      become a leading advocate for and supporter of global health. Nevertheless,
      Japan's engagement with global health has not been outstanding relative to its
      substantial potential, in part because of government fragmentation, a weak civil
      society, and lack of transparency and assessment. Japan's development assistance
      for health, from both governmental and non-governmental sectors, has remained low
      and Japanese global health leadership has been weak. New challenges arising from
      changes in governance and global and domestic health needs, including the recent
      Great East Japan Earthquake, now provide Japan with an opportunity to review past
      approaches to health policy and develop a new strategy for addressing global and
      national health. The fragmented functioning of the government with regards to
      global health policy needs to be reconfigured and should be accompanied by
      further financial commitment to global health priorities, innovative non
      governmental sector initiatives, increased research capacity, and investments in
      good leadership development as witnessed at the G8 Hokkaido Toyako Summit. Should
      this strategy development and commitment be achieved, Japan has the potential to
      make substantial contributions to the health of the world as many countries move
      toward universal coverage and as Japan itself faces the challenge of maintaining
      its own health system.

PMID- 21885097
TI  - Human security and universal health insurance.

PMID- 21885098
TI  - Cost containment and quality of care in Japan: is there a trade-off?
AB  - Japan's health indices such as life expectancy at birth are among the best in the
      world. However, at 8.5% the proportion of gross domestic product spent on health
      is 20th among Organisation for Economic Co-operation and Development countries in
      2008 and half as much as that in the USA. Costs have been contained by the
      nationally uniform fee schedule, in which the global revision rate is set first
      and item-by-item revisions are then made. Although the structural and process
      dimensions of quality seem to be poor, the characteristics of the health-care
      system are primarily attributable to how physicians and hospitals have developed
      in the country, and not to the cost-containment policy. However, outcomes such as
      postsurgical mortality rates are as good as those reported for other developed
      countries. Japan's basic policy has been a combination of tight control of the
      conditions of payment, but a laissez-faire approach to how services are
      delivered; this combination has led to a scarcity of professional governance and
      accountability. In view of the structural problems facing the health-care system,
      the balance should be shifted towards increased freedom of payment conditions by
      simplification of reimbursement rules, but tightened control of service delivery
      by strengthening of regional health planning, both of which should be supported
      through public monitoring of providers' performance. Japan's experience of good
      health and low cost suggests that the priority in health policy should initially
      be improvement of access and prevention of impoverishment from health care, after
      which efficiency and quality of services should then be pursued.

PMID- 21885099
TI  - Population ageing and wellbeing: lessons from Japan's long-term care insurance
      policy.
AB  - Japan's population is ageing rapidly because of long life expectancy and a low
      birth rate, while traditional supports for elderly people are eroding. In
      response, the Japanese Government initiated mandatory public long-term care
      insurance (LTCI) in 2000, to help older people to lead more independent lives and
      to relieve the burdens of family carers. LTCI operates on social insurance
      principles, with benefits provided irrespective of income or family situation; it
      is unusually generous in terms of both coverage and benefits. Only services are
      provided, not cash allowances, and recipients can choose their services and
      providers. Analysis of national survey data before and after the programme
      started shows increased use of formal care at lower cost to households, with
      mixed results for the wellbeing of carers. Challenges to the success of the
      system include dissatisfaction with home-based care, provision of necessary
      support for family carers, and fiscal sustainability. Japan's strategy for long
      term care could offer lessons for other nations.

PMID- 21885100
TI  - Future of Japan's system of good health at low cost with equity: beyond universal
      coverage.
AB  - Japan's premier health accomplishment in the past 50 years has been the
      achievement of good population health at low cost and increased equity between
      different population groups. The development of Japan's policies for universal
      coverage are similar to the policy debates that many countries are having in
      their own contexts. The financial sustainability of Japan's universal coverage is
      under threat from demographic, economic, and political factors. Furthermore, a
      series of crises-both natural and nuclear-after the magnitude 9.0 Great East
      Japan Earthquake on March 11, 2011, has shaken up the entire Japanese social
      system that was developed and built after World War 2, and shown existing
      structural problems in the Japanese health system. Here, we propose four major
      reforms to assure the sustainability and equity of Japan's health accomplishments
      in the past 50 years-implement a human-security value-based reform; redefine the
      role of the central and local governments; improve the quality of health care;
      and commit to global health. Now is the time for rebirth of Japan and its health
      system.

PMID- 21885101
TI  - 50 years of pursuing a healthy society in Japan.

PMID- 21885102
TI  - Suicide in Japan.

PMID- 21885103
TI  - Japan: universal health care at 50 years.

PMID- 21885104
TI  - Keizo Takemi: a catalytic charisma.

PMID- 21885105
TI  - What has made the population of Japan healthy?
AB  - People in Japan have the longest life expectancy at birth in the world. Here, we
      compile the best available evidence about population health in Japan to
      investigate what has made the Japanese people healthy in the past 50 years. The
      Japanese population achieved longevity in a fairly short time through a rapid
      reduction in mortality rates for communicable diseases from the 1950s to the
      early 1960s, followed by a large reduction in stroke mortality rates. Japan had
      moderate mortality rates for non-communicable diseases, with the exception of
      stroke, in the 1950s. The improvement in population health continued after the
      mid-1960s through the implementation of primary and secondary preventive
      community public health measures for adult mortality from non-communicable
      diseases and an increased use of advanced medical technologies through the
      universal insurance scheme. Reduction in health inequalities with improved
      average population health was partly attributable to equal educational
      opportunities and financial access to care. With the achievement of success
      during the health transition since World War 2, Japan now needs to tackle major
      health challenges that are emanating from a rapidly ageing population, causes
      that are not amenable to health technologies, and the effects of increasing
      social disparities to sustain the improvement in population health.

PMID- 21885106
TI  - Kenji Shibuya: promoting global health in Japan.

PMID- 21885107
TI  - Japanese universal health coverage: evolution, achievements, and challenges.
AB  - Japan shows the advantages and limitations of pursuing universal health coverage
      by establishment of employee-based and community-based social health insurance.
      On the positive side, almost everyone came to be insured in 1961; the enforcement
      of the same fee schedule for all plans and almost all providers has maintained
      equity and contained costs; and the co-payment rate has become the same for all,
      except for elderly people and children. This equity has been achieved by
      provision of subsidies from general revenues to plans that enrol people with low
      incomes, and enforcement of cross-subsidisation among the plans to finance the
      costs of health care for elderly people. On the negative side, the fragmentation
      of enrolment into 3500 plans has led to a more than a three-times difference in
      the proportion of income paid as premiums, and the emerging issue of the
      uninsured population. We advocate consolidation of all plans within prefectures
      to maintain universal and equitable coverage in view of the ageing society and
      changes in employment patterns. Countries planning to achieve universal coverage
      by social health insurance based on employment and residential status should be
      aware of the limitations of such plans.

PMID- 21885108
TI  - Science and consensus for health policy making in Japan.

PMID- 21885109
TI  - The value of the National Health and Nutrition Survey in Japan.

PMID- 21885110
TI  - Development of a disaster cardiovascular prevention network.

PMID- 21885111
TI  - Education for health professionals in Japan--time to change.

PMID- 21885112
TI  - Why is Japanese life expectancy so high?

PMID- 21885113
TI  - Nanoparticle-mediated gene transfer specific to retinal pigment epithelial cells.
AB  - Previously, we demonstrated that CK30PEG10k-compacted DNA nanoparticles (NPs)
      efficiently target photoreceptor cells and improve visual function in a retinitis
      pigmentosa model. Here, we test the ability of these NPs in driving transgene
      expression in the retinal pigment epithelium (RPE), using an RPE-specific
      reporter vector (VMD2-eGFP). NPs, uncompacted plasmid, or saline were
      subretinally delivered to adult BALB/c mice. NP-based expression was specific to
      RPE cells and caused no deleterious effects on retinal structure and function.
      eGFP expression levels in NP-injected eyes peaked at post-injection day 2 (PI-2),
      stabilized at levels ~3-fold higher than in naked DNA-injected eyes, and remained
      elevated at the latest time-point examined (PI-30). Unlike naked DNA, which only
      transfected cells at the site of injection, NPs were able to transfect cells
      throughout the RPE. Subretinal injections of rhodamine labeled NPs and naked DNA
      showed comparable initial uptake into RPE cells. However, at PI-7 and -30 days
      significantly more fluorescence was detected inside the RPE of NP-injected eyes
      compared to naked DNA, suggesting NPs are stable inside the cell which could
      possibly lead to higher and sustained expression. Overall, our results
      demonstrate that NPs can efficiently deliver genes to the RPE and hold great
      potential for the treatment of RPE-associated diseases.

PMID- 21885115
TI  - Structural contributions of blocked or grafted poly(2-dimethylaminoethyl
      methacrylate) on PEGylated polycaprolactone nanoparticles in siRNA delivery.
AB  - The multiformity in polymer structure and conformation design provides a great
      potential in improving the gene silencing efficiency of siRNA by polymer vectors.
      In order to provide information on the polymer design for siRNA delivery, the
      structural contributions of blocked or grafted poly(2-dimethylaminoethyl
      methacrylate) on PEGylated polycaprolactone nanoparticles (NPs) in siRNA delivery
      were studied. Herein, two kinds of self-assembly nanoparticles (NPs) formed by
      amphiphilic cationic polymers, methoxy poly(ethylene glycol)-block
      polycaprolactone-block-poly(2-dimethylaminoethyl methacrylate) (mPEG-PCL-b
      PDMAEMA, PECbD) and methoxy poly(ethylene glycol)-block-(polycaprolactone-graft
      poly(2-dimethylaminoethyl methacrylate)) (mPEG-PCL-g-PDMAEMA, PECgD), were used
      to deliver siRNA for in vitro and in vivo studies. The physiochemical properties
      including size and zeta potential of PECbD NPs/siRNA and PECgD NPs/siRNA
      complexes were characterized. In vitro cytotoxicity, cellular uptake and siRNA
      knockdown efficiency were evaluated in HeLa-Luc cells. The endosome escape and
      intracellular distribution of PECbD NPs/siRNA and PECgD NPs/siRNA in HeLa-Luc
      cells were also observed. In vivo polymer mediated siRNA delivery and the
      complexes distribution in isolated organs were studied using mice and tumor
      bearing mice. At the same total degree of polymerization (DP) of DMAEMA, PECgD
      NPs/siRNA complexes possessed higher zeta potentials than PECbD NPs/siRNA
      complexes (at the same N/P ratio), which may be the reason that PECgD NPs/siRNA
      complexes can deliver more siRNA into the cytoplasm and lead to higher in vitro
      luciferase and lamin A/C silencing efficiency than PECbD NPs/siRNA complexes. The
      in vivo imaging measurement and histochemical analysis also confirmed that siRNA
      could be delivered to lungs, livers, pancreas and HeLa-Luc tumors more
      efficiently by PECgD NPs than PECbD NPs. Meanwhile, the PDMAEMA chains of PECgD
      could be shortened which provides benefits for clearing. Therefore, PECgD NPs
      have great potential to be used as efficient non-viral carriers for in vivo siRNA
      delivery.

PMID- 21885114
TI  - Characterization of the effects of x-ray irradiation on the hierarchical
      structure and mechanical properties of human cortical bone.
AB  - Bone comprises a complex structure of primarily collagen, hydroxyapatite and
      water, where each hierarchical structural level contributes to its strength,
      ductility and toughness. These properties, however, are degraded by irradiation,
      arising from medical therapy or bone-allograft sterilization. We provide here a
      mechanistic framework for how irradiation affects the nature and properties of
      human cortical bone over a range of characteristic (nano to macro) length-scales,
      following x-ray exposures up to 630 kGy. Macroscopically, bone strength,
      ductility and fracture resistance are seen to be progressively degraded with
      increasing irradiation levels. At the micron-scale, fracture properties,
      evaluated using insitu scanning electron microscopy and synchrotron x-ray
      computed micro-tomography, provide mechanistic information on how cracks interact
      with the bone-matrix structure. At sub-micron scales, strength properties are
      evaluated with insitu tensile tests in the synchrotron using small-/wide-angle x
      ray scattering/diffraction, where strains are simultaneously measured in the
      macroscopic tissue, collagen fibrils and mineral. Compared to healthy bone,
      results show that the fibrillar strain is decreased by ~40% following 70 kGy
      exposures, consistent with significant stiffening and degradation of the
      collagen. We attribute the irradiation-induced deterioration in mechanical
      properties to mechanisms at multiple length-scales, including changes in crack
      paths at micron-scales, loss of plasticity from suppressed fibrillar sliding at
      sub-micron scales, and the loss and damage of collagen at the nano-scales, the
      latter being assessed using Raman and Fourier Transform Infrared spectroscopy and
      a fluorometric assay.

PMID- 21885116
TI  - The use of computational fluid dynamic models for the optimization of cell
      seeding processes.
AB  - The seeding of a porous scaffold with stem cells is a fundamental step in
      engineering sizeable tissue constructs that are clinically viable. However, a key
      problem often encountered is inhomogeneous seeding of the cells particularly when
      the cells are delivered through the thickness of the scaffold. The objective of
      this study was to establish the quantitative relationships between the cell
      seeding efficiency and the initial vacuum pressure in a compact perfusion seeding
      device that uses the effect of differential pressure induced by vacuum to seed
      cells on a porous scaffold. A transient CFD solution of the fluid flow in the
      device was used to optimize the initial vacuum pressure for efficient cell
      seeding. Results indicate that the optimal initial vacuum pressure for homogenous
      cell seeding is approximately -20 kPa for the seeding device. This study presents
      a 3-D computational model that can be employed in designing and optimizing cell
      seeding techniques and corresponding technology.

PMID- 21885117
TI  - Combined chemical and topographical guidance cues for directing cytoarchitectural
      polarization in primary neurons.
AB  - Chemical and topographical cues can be used to guide dissociated neurons into
      user-defined network geometries on artificial substrates, yet control of neuron
      polarity (differentiation into axons and dendrites) remains an elusive goal. We
      developed a dual guidance cue strategy for directing morphological maturity in
      neurons in vitro using combined chemical and topographical guidance cues on glass
      substrates. The surface chemistry provides chemical attraction and repulsion for
      controlling neuron placement and outgrowth, while the topography provides
      additional surface area for neuron attachment. Poly-l-lysine (PLL) was adsorbed
      into etched trenches in glass substrates, and an acetone liftoff process was used
      to produce bifunctional surfaces with a hydrophobic hexamethyldisilazane (HMDS)
      background and trench patterns of PLL. We examined the cytoarchitectural
      polarization of dissociated hippocampal pyramidal neurons on guidance cues
      designed to promote rapid outgrowth of neurites onto continuous line features and
      delayed neurite outgrowth onto interrupted line features. An optimum distance of
      approximately 5 MUm between the cell body attachment node and the first
      interrupted line guidance cue led to specific cytoarchitectural polarization of
      >=60% of neurons by 3 days of culture in vitro.

PMID- 21885118
TI  - Induction of immunotolerance via mPEG grafting to allogeneic leukocytes.
AB  - The induction of anergy or tolerance to prevent allorecognition is of clinical
      interest. To this end, the effects of methoxypoly(ethylene glycol) [mPEG]
      grafting to allogeneic lymphocytes on proliferation and phenotype (Th17 and Treg)
      was examined in vitro and in vivo. Control studies demonstrated that PEGylation
      did not affect cells viability or proliferation (mitogen) potential. Conditioned
      media (1 degrees  MLR) collected at 72 h from resting PBMC demonstrated no
      immunomodulatory effects whereas the control MLR demonstrated significant (p <
      0.001) pro-proliferative potential and significantly increased in IL-2, TNF
      alpha, and INF-gamma. However, 1 degrees  media from either resting mPEG-PBMC or
      the PEGylated MLR resulted in a significant inhibitory effect (p < 0.001) in the
      2 degrees  MLR and no increase in cytokines. PEGylation of donor murine
      splenocytes resulted in significant in vivo immunosuppressive effects in H2
      disparate mice. While unmodified allogeneic splenocytes resulted in a significant
      in vivo decrease in Treg and increased Th17 lymphocytes, PEGylated allogeneic
      splenocytes yielded significantly increased Tregs and baseline levels of Th17
      lymphocytes. This effect was persistent to at least 30 days post challenge and
      was not reversed by unmodified allogeneic cells. These studies demonstrate that
      PEGylation of allogeneic lymphocytes induced an immunoquiescent state both in
      vitro and in vivo.

PMID- 21885119
TI  - The amelioration of cardiac dysfunction after myocardial infarction by the
      injection of keratin biomaterials derived from human hair.
AB  - Cardiac dysfunction following acute myocardial infarction is a major cause of
      advanced cardiomyopathy. Conventional pharmacological therapies rely on prompt
      reperfusion and prevention of repetitive maladaptive pathways. Keratin
      biomaterials can be manufactured in an autologous fashion and are effective in
      various models of tissue regeneration. However, its potential application in
      cardiac regeneration has not been tested. Keratin biomaterials were derived from
      human hair and its structure morphology, carryover of beneficial factors,
      biocompatibility with cardiomyocytes, and in vivo degradation profile were
      characterized. After delivery into infarcted rat hearts, the keratin scaffolds
      were efficiently infiltrated by cardiomyocytes and endothelial cells. Injection
      of keratin biomaterials promotes angiogenesis but does not exacerbate
      inflammation in the post-MI hearts. Compared to control-injected animals, keratin
      biomaterials-injected animals exhibited preservation of cardiac function and
      attenuation of adverse ventricular remodeling over the 8 week following time
      course. Tissue western blot analysis revealed up-regulation of beneficial factors
      (BMP4, NGF, TGF-beta) in the keratin-injected hearts. The salient functional
      benefits, the simplicity of manufacturing and the potentially autologous nature
      of this biomaterial provide impetus for further translation to the clinic.

PMID- 21885120
TI  - Selective antileukemia effect of stabilized nanohybrid vesicles based on
      cholesteryl succinyl silane.
AB  - A nanohybrid vesicle was developed from cholesteryl succinyl silane(CSS) in
      combination of sol-gel process and self-assembly technique. The silicalike
      surface adds CSS vesicles remarkably high stability against destabilization in
      blood or leakage of drug cargos. It was found that CSS vesicles alone exhibited
      selective antiproliferative effects on leukemia cells without destroying normal
      blood cells. In addition, they are able to encapsulate not only hydrophilic guest
      species inside the inner water compartment but also hydrophobic molecules in the
      cholesteryl succinyl bilayer membrane. More importantly, CSS vesicles loaded with
      doxorubicin enhanced the anticancer efficiency of cancer therapeutics greatly
      while minimizing the use of inactive materials and lowering the exposure of
      normal cells to toxic side effects. This makes CSS vesicle a promising carrier
      for the treatment of cancer, especially for leukemia.

PMID- 21885121
TI  - Selective adhesion and growth of vascular endothelial cells on bioactive peptide
      nanofiber functionalized stainless steel surface.
AB  - Metal-based scaffolds such as stents are the most preferred treatment methods for
      coronary artery disease. However, impaired endothelialization on the luminal
      surface of the stents is a major limitation occasionally leading to catastrophic
      consequences in the long term. Coating the stent surface with relevant bioactive
      molecules is considered to aid in recovery of endothelium around the wound site.
      However, this strategy remains challenging due to restrictions in availability of
      proper bioactive signals that will selectively promote growth of endothelium and
      the lack of convenience for immobilization of such signaling molecules on the
      metal surface. In this study, we developed self-assembled peptide nanofibers that
      mimic the native endothelium extracellular matrix and that are securely
      immobilized on stainless steel surface through mussel-inspired adhesion
      mechanism. We synthesized Dopa-conjugated peptide amphiphile and REDV-conjugated
      peptide amphiphile that are self-assembled at physiological pH. We report that
      Dopa conjugation enabled nanofiber coating on stainless steel surface, which is
      the most widely used backbone of the current stents. REDV functionalization
      provided selective growth of endothelial cells on the stainless steel surface.
      Our results revealed that adhesion, spreading, viability and proliferation rate
      of vascular endothelial cells are remarkably enhanced on peptide nanofiber coated
      stainless steel surface compared to uncoated surface. On the other hand, although
      vascular smooth muscle cells exhibited comparable adhesion and spreading profile
      on peptide nanofibers, their viability and proliferation significantly decreased.
      Our design strategy for surface bio-functionalization created a favorable
      microenvironment to promote endothelial cell growth on stainless steel surface,
      thereby providing an efficient platform for bioactive stent development for long
      term treatment of cardiovascular diseases.

PMID- 21885122
TI  - Periodontal regeneration using a bilayered PLGA/calcium phosphate construct.
AB  - The regeneration of tissues affected by periodontal disease is a complex process;
      it encompasses the formation of bone, cementum and periodontal ligament. We
      developed a semi-rigid PLGA (polylactide-co-glycolide acid)/CaP (calcium
      phosphate) bilayered biomaterial construct to promote periodontal regeneration,
      which has a continuous outer barrier membrane and an inner topographically
      complex component. Our experimental model compared periodontal prophylaxis alone
      with prophylaxis and biomaterial implantation in the treatment of class II
      furcation defects in dogs. Clinical evaluation, micro-computed tomography,
      histology and backscattered electron imaging were used for data analysis. Healing
      occurred uneventfully and bone volumetric values, trabecular number and
      trabecular thickness were all significantly greater in the treated group; while
      trabecular separation was significantly greater in the control group. New
      cementum, bone, and periodontal ligament with Sharpey fibre insertions were only
      seen in the treated group. Although periodontal regeneration has been reported
      elsewhere, the advantages of employing our bilayered PLGA + CaP construct are
      twofold: 1)it did not collapse into the defect; and, 2) its inner side was able
      to retain the blood clot throughout the buccal defect. The result was greater
      periodontal regeneration than has previously been reported with traditional
      flexible membranes.

PMID- 21885123
TI  - SIE, SIES, GITMO updated clinical recommendations for the management of chronic
      lymphocytic leukemia.
AB  - By using GRADE system we updated the guidelines for management of CLL issued in
      2006 from SIE, SIES and GITMO group. We recommended fludarabine,
      cyclophosphamide, rituximab (FCR) in younger and selected older patients with a
      good fitness status, no unfavourable genetics (deletion 17p and/or p53
      mutations), and a less toxic treatment in nonfit and elderly patients. In
      patients without unfavourable genetics, relapsed after 24 months the same initial
      treatment including rituximab can be considered. In patients with unfavourable
      genetics, refractory or relapsed within 24 months from a prior fludarabine-based
      treatment, allogeneic SCT or experimental treatments should be given.

PMID- 21885124
TI  - Association of KIR2DS4 gene with susceptibility to leukemia: Chinese-Polish
      discrepancy.

PMID- 21885125
TI  - Towards a scheme of toxic equivalency factors (TEFs) for the acute toxicity of
      PAHs in sediment.
AB  - Toxic equivalency factors/quotients (TEF/TEQs) express the toxicity of complex
      mixtures. For PAHs, TEF values are available for assessing their carcinogenic
      potential and are expressed as benzo[a]pyrene equivalents. This study develops a
      similar approach for their acute toxicity in sediments. Acute toxicity (10 day
      EC50) values were generated using the marine amphipod Corophium volutator
      bioassay for twelve low molecular weight PAHs. The results ranged from 24 to >
      1000 mg/Kg sediment dry weight for 4-methyldibenzothiophene and anthracene,
      respectively. Phenanthrene was used as the reference compound (TEF=1) and so the
      TEQ values derived are expressed as phenanthrene equivalents. In order to
      illustrate the applicability of this approach to the development of marine
      indicators we plotted TEQ values for acute toxicity to UK environmental
      monitoring data. Further work is required to validate the TEF values produced and
      to extend the TEQ approach to include a wider range of low molecular weight PAHs.

PMID- 21885126
TI  - Retrospective analysis of real-world efficacy of angiotensin receptor blockers
      versus other classes of antihypertensive agents in blood pressure management.
AB  - BACKGROUND: Efficacy of blood pressure (BP) lowering may differ between clinical
      trials and what is observed in clinical practice. These differences may
      contribute to poor BP control rates among those at risk. OBJECTIVE: We conducted
      an observational study to determine the BP-lowering efficacy of angiotensin
      receptor blocker (ARB) versus non-ARB-based antihypertensive treatments in a
      large Canadian primary care database. METHODS: We analyzed the South Western
      Ontario database of 170,000 adults (aged >18 years) with hypertension persisting
      with antihypertensive medication for >=9 months. Routine standard of care office
      BP was measured using approved manual aneroid or automated devices. BP <140 mm Hg
      and/or <90 mm Hg <=9 months after treatment initiation, persistence (presence of
      initial antihypertensive prescription at the first, second, third, and fourth
      year anniversary) with antihypertensive therapy, and the presence of a
      cardiovascular (CV) event (ie, myocardial infarction) were studied. RESULTS:
      After 9 months of monotherapy, 28% (978 of 3490) of patients on ARBs achieved
      target BP versus 27% (839 of 3110) on angiotensin-converting enzyme inhibitors
      (ACEIs) (P > 0.05), 26% (265 of 1020) on calcium channel blockers (CCBs) (P >
      0.05), 21% (221 of 1050) on beta-blockers (P = 0.002), and 19% (276 of 1450) on
      diuretics (P = 0.001). Attainment rates were significantly higher with irbesartan
      (38%; 332 of 873) versus losartan (32%; 335 of 1047; P = 0.01), valsartan (19%;
      186 of 977; P = 0.001), and candesartan (25%; 148 of 593; P = 0.001). BP goal
      attainment rates were significantly higher when ARB was compared with non-ARB
      based dual therapy (39%; 1007 of 2584 vs 31%; 1109 of 3576; P = 0.004);
      irbesartan + hydrochlorothiazide (HCTZ) was significantly higher than losartan +
      HCTZ (36%; 500 of 1390 vs 20%; 252 of 1261; P = 0.001). For patients receiving
      dual or tri-therapy, 48% (667 of 1390) of patients receiving irbesartan reached
      target BP versus 41% to 42% for losartan (517 of 1261), valsartan (194 of 462),
      and candesartan (168 of 401) (P = 0.001 for each). After 4 years, persistence
      rates were not statistically different among ARB, CCB, and diuretic
      monotherapies, but appeared somewhat higher with ACEIs and beta-blockers (78%,
      78%, 79%, 91%, and 84%, respectively). Persistence was not significantly
      different between irbesartan and losartan monotherapy (76% for both; P > 0.05),
      but was significantly higher with irbesartan + HCTZ versus losartan + HCTZ (96%
      vs 73%, respectively; P = 0.001). Patients treated with ARBs reported fewer CV
      events than those receiving ACEIs or CCBs (4.3% vs 7.0% and 11.0%, respectively;
      P < 0.001). Within the ARB class, the lowest rate was with irbesartan (3.0% vs
      4.6%-5.0% for other ARBs; P < 0.02). CONCLUSIONS: In this real-world setting,
      hypertensive adults treated with ARBs versus beta-blockers or diuretics were more
      likely to have evidence-based target BP recorded. In addition, patients using
      ARBs versus ACEIs or CCBs had fewer reports of CV events.

PMID- 21885127
TI  - The region of largest beta-zone parapapillary atrophy area predicts the location
      of most rapid visual field progression.
AB  - PURPOSE: To determine if visual field (VF) progression occurs most rapidly in the
      region of largest beta-zone parapapillary atrophy (PPA). DESIGN: Retrospective
      cohort. PARTICIPANTS: One hundred twenty-five patients from the New York Glaucoma
      Progression Study with both beta-zone PPA and VF progression. METHODS: Treated
      open-angle glaucoma patients with 8 or more Swedish Interactive Threshold
      Algorithm Standard 24-2 VFs (Humphrey Field Analyzer II; Carl Zeiss Meditec,
      Inc., Dublin, CA) in either eye were identified. Eyes with optic disc
      photographs, beta-zone PPA, less than 6 diopters myopia, and VF progression were
      studied. Visual field progression was defined using trend analysis as the
      presence of at least 2 adjacent progressing points in the same hemifield using
      standard pointwise linear regression (PLR) criteria. MAIN OUTCOME MEASURES: The
      correlation between beta-zone PPA and location of most rapid future VF
      progression. RESULTS: One hundred twenty-five eyes (125 patients; mean age, 71.9
      +/- 12.3 years; 58% women; 75% European descent) with beta-zone PPA and VF
      progression were enrolled. The mean follow-up was 6.8 +/- 1.7 years and the mean
      number of VFs was 12.5 +/- 3.6. Ninety-three patients (74%) had more beta-zone
      PPA inferiorly and 32 patients (26%) had more beta-zone PPA superiorly. The
      fastest VF progression occurred in the superior hemifield in 77 patients (62%)
      and in the inferior hemifield in 48 (38%) patients. Patients with superior VF
      progression had a superior localized mean rate of progression of -1.57 +/- 1.7
      dB/year, and patients with inferior VF progression had an inferior localized mean
      rate of -0.94 +/- 1.4 dB/year (P = 0.012). The mean number of points reaching the
      predefined PLR end points was 5.6+/-7.5 for the superior VF hemifield and 3.0+/
      4.9 for the inferior hemifield (P = 0.006). The hemifield with more points
      reaching PLR progression end points, with fastest average velocity of
      progression, or both was spatially consistent with the location of largest beta
      zone PPA in 89 (71%) patients (P = 0.0001, Fisher exact test; kappa = 0.35; 95%
      confidence interval, 0.17-0.53). CONCLUSIONS: In treated glaucoma patients with
      beta-zone PPA and VF progression, the location of largest beta-zone PPA typically
      correlates spatially with the region of the most rapid future VF progression.
      FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest
      in any materials discussed in this article.

PMID- 21885128
TI  - Meta-review of depressive subtyping models.
AB  - BACKGROUND: Increasing dissatisfaction with the non-specificity of major
      depression has led many to propose more specific depressive subtyping models. The
      present meta-review seeks to map dominant depressive subtype models, and
      highlight definitions and overlaps. METHODS: A database search in Medline and
      EMBASE of proposed depressive subtypes, and limited to reviews published between
      2000 and 2011, was undertaken. Of the more than four thousand reviews, 754 were
      judged as potentially relevant and provided the base for the present selective
      meta-review. RESULTS: Fifteen subtype models were identified. The subtypes could
      be divided into five molar categories of (1) symptom-based subtypes, such as
      melancholia, psychotic depression, atypical depression and anxious depression,
      (2) aetiologically-based subtypes, exemplified by adjustment disorders, early
      trauma depression, reproductive depression, perinatal depression, organic
      depression and drug-induced depression, (3) time of onset-based subtypes, as
      illustrated by early and late onset depression, as well as seasonal affective
      disorder, (4) gender-based (e.g. female) depression, and (5) treatment resistant
      depression. An overview considering definition, bio-psycho-social correlates and
      the evidence base of treatment options for each subtype is provided. LIMITATIONS:
      Despite the large data base, this meta-review is nevertheless narrative focused.
      CONCLUSIONS: Subtyping depression is a promising attempt to overcome the non
      specificity of many diagnostic constructs such as major depression, both in
      relation to their intrinsic non-specificity and failure to provide treatment
      specific information. If a subtyping model is to be advanced it would need,
      however, to demonstrate differential impacts of causes and treatments.

PMID- 21885129
TI  - Mycobacterium indicus pranii is a potent immunomodulator for a recombinant
      vaccine against human chorionic gonadotropin.
AB  - The objective of this work was to identify a human use-permissible adjuvant to
      enhance significantly the antibody response to a recombinant anti-hCG vaccine.
      Previous Phase II efficacy trials in sexually active women have demonstrated the
      prevention of pregnancy at hCG bioneutralization titers of 50ng/ml or more.
      Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium employed as an
      autoclaved suspension in aqueous buffer, significantly increased antibody titers
      in the FVB strain of mice. Three other genetic strains of mice: SJL, C3H, and
      C57Bl/6 responded with antibody titers several-fold higher than 50 ng/ml, which
      is the protective threshold in women, although there were differences in the peak
      titers attained. In addition, the duration of the antibody response was
      lengthened. The vaccine hCGbeta-LTB, given together with MIP, induces both a Th1
      and Th2 response, which is reflected in the production of not only IgG1, but also
      a high proportion of IgG2a and IgG2b antibodies.

PMID- 21885130
TI  - Psychosis and smoking cessation: difficulties in quitting associated with sex and
      substance abuse.
AB  - No prospective studies of first psychotic episodes have explored sex differences
      in smoking cessation. The aim of this study was to determine the influence of sex
      and substance abuse on smoking cessation during an 8-year follow-up of patients
      after a first psychotic episode. Logistic regression modeling was used to
      identify factors associated with smoking cessation by sex. To examine for sex
      variable interactions, the following two methods were used: 1) for other clinical
      variables, mixed analyses were calculated; and 2) for use of other substances,
      logistic regression models were performed only in the substance users. At
      baseline, 79% of men and 84% of women were current smokers. Lower smoking
      cessation after 8 years was associated with female sex (odds ratio, OR=0.30; 95%
      confidence intervals, CIs=0.12-0.75) and treatment with typical antipsychotics
      (OR=0.30, CIs=0.10-0.93). In a logistic regression model of alcohol users, those
      who used alcohol continuously were less likely to stop smoking (adjusted OR=0.22,
      CI=0.05-1.0). Among patients who continued using cannabis, female sex was
      associated with significant lower smoking cessation (adjusted OR=0.03, CI=0.001
      0.77). Sex may act as a moderator in smoking cessation after a first psychotic
      episode. Smoking cessation interventions in these patients should consider sex
      differences and comorbidity with alcohol and cannabis use.

PMID- 21885131
TI  - Transfer of maternal haptoglobin to suckling piglets.
AB  - The acute phase protein haptoglobin (Hp) exerts immune modulating functions in
      the innate and adaptive immune system. In pigs, serum Hp concentrations are
      linked to impaired growth performance. There is little information on Hp in
      newborn piglets and the onset of endogenous Hp synthesis. In the first experiment
      we analyzed Hp concentrations in colostrum from sows (n=5) and serum from their
      off-spring (n=43) during the first 12h of life. The piglets were divided in a
      colostrum group which was allowed to suckle and a colostrum-deprived group which
      received a Hp-free milk replacer. We were able to show that serum Hp in newborn
      piglets increased 3h after colostrum intake whereas serum Hp remained low in
      colostrum-deprived littermates. The absorption of colostral Hp in the jejunum
      could be shown via immunohistochemistry. In colostrum suckled piglets, endogenous
      Hp synthesis in the liver increased 9h after birth, no increase in Hp mRNA was
      observable during the first 12h of life in colostrum-deprived piglets. From our
      results we concluded that maternal Hp is transferred to newborn pigs via
      colostrum and the stimulus for the increase in Hp synthesis is mediated by
      colostrum. In a second experiment we analyzed Hp in colostrum, milk and serum
      from sows (n=43) and their off-spring (n=442) from birth until weaning.
      Haptoglobin was high in colostrum (1.11 +/- 0.10mg/ml) and declined to lower but
      stable milk levels (0.36 +/- 0.08 mg/ml) until weaning. Colostral Hp and daily
      litter weight gain were negatively correlated (r=-0.5, p<0.01) whereas the
      relationship between piglets serum Hp and daily weight gain was weaker (r=-0.22,
      p<0.05). We therefore speculate that maternal Hp exerts systemic actions in
      piglets.

PMID- 21885132
TI  - Leukotriene synthesis inhibitor decreases vasopressin release in the early phase
      of sepsis.
AB  - The aim was to analyze the effect of leukotriene synthesis inhibitor administered
      intraperitoneally in vasopressin release during sepsis. Male Wistar rats received
      injections of MK-886 (1.0, 2.0 or 4.0 mg/kg) or vehicle (DMSO 5%) 1 h before
      cecal ligation and puncture. There was some variation on the survival rate
      depending on the dose used but the drug did not modify the hematocrit,
      osmolality, serum sodium and nitrate, plasma protein, and neutrophil recruitment,
      in any dose. Nevertheless, vasopressin (AVP) release decreased in a dose-response
      manner in the early phase of sepsis. These results support the suggestion that
      leukotrienes (LTs) are involved in AVP release during sepsis.

PMID- 21885133
TI  - Antihypertensive drug-induced angioedema causing upper airway obstruction in
      children.
AB  - OBJECTIVE: Angioedema is a well-described complication arising from the use of
      antihypertensive agents in the adult population. However, its occurrence and
      potential for upper airway compromise in pediatrics has only been sporadically
      reported in the literature. Our objective is to report and review the occurrence
      of antihypertensive-induced angioedema in the pediatric population and the
      potential for airway compromise. METHODS: Charts of 42 patients admitted to
      Cincinnati Children's Hospital Medical Center with the discharge diagnosis of
      angioedema (ICD-9 code 995.1) from January 2000 to January 2010 were reviewed. Of
      the 42 charts, 3 cases had angioedema induced by antihypertensive drugs and all 3
      resulted in upper airway obstruction. Summary and findings of the data collected
      from the medical chart review included demographics, chief complaint(s), past
      medical history, hospital course, antihypertensive drugs used, diagnostic
      test(s), medical treatment, and time from onset of symptoms to resolution. In
      addition, a PubMed literature search using the terms angioedema and
      antihypertensive drugs was performed to review its occurrence in pediatrics. The
      previous literature case reports were compared to our cases to further
      characterize and emphasize the clinical features of this occurrence in children
      and adolescents. RESULTS: Despite the well-known occurrence of antihypertensive
      drug-induced angioedema causing airway obstruction in adults, only 4 case reports
      have been previously published in children. At our institution, we describe 3
      children who developed acute angioedema with upper airway obstruction after the
      chronic use of antihypertensive medications [2 drugs in the ACE inhibitor class
      (enalapril and lisinopril), and 1 drug in the calcium channel blocker class (CCB;
      amlodipine)]. In all 3 cases, the symptoms resolved within 1 week after the
      antihypertensive agent was discontinued. CONCLUSION: Upper airway obstruction can
      occur at any age when taking antihypertensive drugs. Particular caution should be
      applied to ACE inhibitors and CCBs in this regard. With the increasing use of
      antihypertensive agents in the pediatric population, clinicians should be alert
      to the possibility of angioedema with upper airway obstruction as a potential
      lethal adverse effect.

PMID- 21885134
TI  - ECG findings in comparison to cardiovascular MR imaging in viral myocarditis.
AB  - OBJECTIVES: We sought (1) to assess prevalence and type of ECG abnormalities in
      patients with biopsy proven myocarditis and signs of myocardial damage indicated
      by LGE, and (2) to evaluate whether ECG abnormalities are related to the pattern
      of myocardial damage. BACKGROUND: Prevalence and type of ECG abnormalities in
      patients presenting biopsy proven myocarditis, as well as any relation between
      ECG abnormalities and the in vivo pattern of myocardial damage are unknown.
      METHODS: Eighty-four consecutive patients fulfilled the following criteria: (1)
      newly diagnosed biopsy proven viral myocarditis, and (2) non-ischemic LGE, and
      (3) standard 12-lead-ECG upon admission. RESULTS: Sixty-five patients with biopsy
      proven myocarditis had abnormal ECGs upon admission (77%). In this group, ST
      abnormalities were detected most frequently (69%), followed by bundle-branch
      block in 26%, and Q-waves in 8%. Atrial fibrillation was present in 6%, and AV
      Block in two patients. In patients with septal LGE ST-abnormalities were more
      frequently located in anterolateral leads compared to patients with lateral LGE,
      in whom ST-abnormalities were most frequently observed in inferolateral leads.
      Bundle-branch-block occurred more often in patients with septal LGE (11/17). Four
      of five patients with Q-waves had severe and almost transmural LGE in the lateral
      wall. CONCLUSION: ECG abnormalities can be found in most patients with biopsy
      proven viral myocarditis at initial presentation. However, similar to suspected
      acute myocardial infarction, a normal ECG does not rule out myocarditis. ECG
      findings are related to the amount and area of damage as indicated by LGE, which
      confirms the important clinical role of ECG.

PMID- 21885135
TI  - Toxoplasma gondii in Romanian household cats: evaluation of serological tests,
      epidemiology and risk factors.
AB  - Felines are the key species in the epidemiology of Toxoplasma gondii infection,
      as they are the definitive host of the parasite and are the only species that can
      shed resistant oocysts in the environment. Different assays are in use for the
      detection of antibodies against T. gondii in cats. However, assay validation
      studies are limited. For that reason it was our aim to first evaluate 6
      serological tests (one commercial and 2 in-house ELISAs, ImmunoComb, IFAT and
      MAT) for antibodies (IgG) against T. gondii in cats by Bayesian modeling. Factors
      associated with seropositivity were evaluated by bivariable and multivariable
      methods. The test evaluation indicated the commercial ELISA had the highest
      Youden Index. The estimated sensitivity ranged between 95.7% and 97.1% and the
      specificity between 97.3% and 97.6%. Using this commercial ELISA 111 out of 236
      cats (47%) were positive for T. gondii antibodies. Two peaks in the percentage of
      strong positive samples (S/P>=200) were observed, around 10-months-old and 8
      years-old. In bivariable analysis the seroprevalence was significantly higher in
      adult cats, cats with mixed diet, with outdoor access, in cats from a rural area
      and in cats from centre and north-western Romania. Adult age (adults: OR 6.98;
      95% CI: 2.02-24.14 and geriatrics (cats older than 10-years): OR 12.01; 95% CI:
      1.60-90.15) and outdoor access (OR 6.38; 95% CI: 2.32-17.53) remained significant
      risk factors in the multivariable logistic regression analysis. Our results
      suggest that T. gondii infection is common in household cats in Romania, and
      especially in those with outdoor access.

PMID- 21885136
TI  - Relationship between somatic cell count status and subsequent clinical mastitis
      in Dutch dairy cows.
AB  - High composite somatic cell counts (CSCC) in dairy cows may develop into clinical
      mastitis (CM), suggesting that prevention or intervention of high CSCC may
      prevent CM later in lactation. The objective of this study was to quantify the
      relationship between high CSCC in dairy cows and the first subsequent case of CM
      in the same lactation. Farmer-diagnosed cases of CM and test day CSCC
      measurements during 1 year of 13,917 cows in 196 randomly selected Dutch dairy
      herds were available for analysis. Cows were followed in 1 lactation from the
      first test day postpartum until CM, drying off, culling or end of study. Cox
      proportional hazards models with time-varying CSCC levels were used to estimate
      the effect of high CSCC (>=200,000cells/ml) on the time until the first case of
      CM. A shared frailty effect was included to adjust for clustering of cows within
      herds. The proportion of cows developing CM after a CSCC measurement was 11%.
      Primiparae with a high CSCC had a 4-fold higher hazard for subsequent CM than
      primiparae with a low CSCC; multiparae with a high CSCC had a 2-fold higher
      hazard than multiparae with a low CSCC. Additionally, multiparae with a low CSCC
      had a 2-fold higher hazard for CM occurrence than primiparae with a low CSCC.
      Increasing the threshold for high CSCC showed that the risk for CM increased. If
      the last CSCC before CM was low, CSCC information of 2 preceding test days was
      more predictive than CSCC information from only the last test day. When the last
      CSCC was high, CSCC information of 2 preceding test days did not have added
      predictive value. This study identified that approximately 25% of first
      subsequent CM cases after a CSCC measurement can potentially be prevented when
      cows are prevented to get high CSCC or when high CSCC cows are removed from the
      population. This corresponded with a decrease in the proportion of lactating cows
      with CM after a CSCC measurement from 11% to 7%.

PMID- 21885137
TI  - A nonparametric vs. latent class model of general practitioner utilization:
      evidence from Canada.
AB  - Predicting health care utilization is the foundation of many health economics
      analyses, such as calculating risk-adjustment capitation payments or measuring
      equity in health care utilization. The most common econometric models of
      physician utilization are parametric count data models, since the most common
      metric of physician utilization is the number of physician visits. This paper
      makes two distinct contributions to the literature analyzing GP utilization: (i)
      it is the first to use a nonparametric kernel conditional density estimator to
      model GP utilization and compare the predicted utilization with that from a
      latent class negative binomial model; and (ii) it uses panel data to control for
      the potential endogeneity between self-reported health status and the number of
      GP visits. The goodness-of-fit results show the kernel conditional density
      estimator provides a better fit to the observed distribution of GP visits than
      the latent class negative binomial model. There are some meaningful differences
      in how the predicted conditional mean number of GP visits changes with a change
      in an individual's characteristics, called the incremental effect (IE), between
      the kernel conditional density estimator and the latent class negative binomial
      model. The most notable differences are observed in the right tail of the
      distribution where the IEs from the latent class negative binomial model are up
      to 190 times the magnitude of the IEs from the kernel conditional density
      estimator.

PMID- 21885138
TI  - The impact of Medicaid insurance coverage on dental service use.
AB  - The new comprehensive health reform, beginning in 2014, will require Medicaid to
      expand all elements of coverage to individuals with incomes up to 133 percent of
      the federal poverty line. With millions more individuals gaining eligibility for
      adult Medicaid dental benefits, generating an unbiased estimate of the elasticity
      of demand for dental services is critical. The causal relationship between access
      to adult Medicaid dental benefits and usage of dental services for low-income
      adults is estimated, using difference-in-differences estimation procedures to
      exploit the state-level variation in adult Medicaid dental benefits. Results
      suggest that adult Medicaid dental benefits increase the probability of a dental
      visit within 12 months by 16.4-22 percent. A variety of robustness checks are
      invoked to confirm the finding.

PMID- 21885139
TI  - External beam radiotherapy combined with intraluminal brachytherapy in esophageal
      carcinoma.
AB  - PURPOSE: To assess the effectiveness of definitive radiation therapy in patients
      with potentially curable esophageal cancer and to evaluate the side-effects of
      this treatment. METHODS AND MATERIALS: Sixty-two patients with esophageal cancer,
      who were treated with definitive, curatively intended radiotherapy consisting of
      external radiotherapy (60 Gy in 30 fractions), preceded and followed by LDR or
      HDR intraluminal brachy (12 Gy in 2 fractions) were retrospectively analyzed.
      RESULTS: Recurrences were reported in 38 patients (61%), of which 25 (64%) failed
      locally first. The overall survival rates at 1, 2 and 5 years were 57%, 34% and
      11%, respectively. The median overall survival was 15 months. No prognostic
      factors could be identified. Most frequently reported treatment related
      toxicities were esophagitis, ulcerations, (11%) and strictures (16%). In 10
      patients (16%) severe toxicities, were reported including grade III ulceration (2
      cases), stricture (1 case), radiation pneumonitis (1 case), perforation (1 case),
      esophageal-pleural-tracheal fistula (1 case), and acute esophageal bleeding (4
      cases). A history of gastrectomy was significantly associated with the
      development of severe toxicity. CONCLUSION: Curatively intended radiotherapy
      alone can be offered to esophageal cancer patients, even when surgery and/or
      chemotherapy are not feasible. However, we observed severe toxicity in a
      substantial part of the patients. Given the relatively high rate of severe
      complications and the uncertainties regarding dose escalation, the addition of
      brachytherapy, with consequently high surface doses, should be limited to well
      selected patients.

PMID- 21885140
TI  - Trans-abdominal ultrasound (US) and magnetic resonance imaging (MRI) correlation
      for conformal intracavitary brachytherapy in carcinoma of the uterine cervix.
AB  - PURPOSE: Trans-abdominal ultrasonography (US) is capable of determining size,
      shape, thickness, and diameter of uterus, cervix and disease at cervix or
      parametria. To assess the potential value of US for image-guided cervical cancer
      brachytherapy, we compared US-findings relevant for brachytherapy to the
      corresponding findings obtained from MR imaging. MATERIALS AND METHODS: Twenty
      patients with biopsy proven cervical cancer undergoing definitive radiotherapy
      with/without concomitant Cisplatin chemotherapy and suitable for brachytherapy
      were invited to participate in this study. US and MR were performed in a similar
      reproducible patient positioning after intracavitary application. US mid-sagittal
      and axial image at the level of external cervical os was acquired. Reference
      points D1 to D9 and distances were identified with respect to central tandem and
      flange, to delineate cervix, central disease, and external surface of the uterus.
      RESULTS: Thirty-two applications using CT/MR compatible applicators were
      evaluable. The D1 and D3 reference distances which represent anterior surface had
      a strong correlation with R=0.92 and 0.94 (p<0.01). The D2 and D4 reference
      distances in contrast, which represent the posterior surface had a moderate (D2)
      and a strong (D4) correlation with R=0.63 and 0.82 (p<0.01). Of all, D2 reference
      distance showed the least correlation of MR and US. The D5 reference distance
      representing the fundal thickness from tandem tip had a correlation of 0.98. The
      reference distances for D6, D7, D8, and D9 had a correlation of 0.94, 0.82, 0.96,
      and 0.93, respectively. CONCLUSIONS: Our study evaluating the use of US, suggests
      a reasonably strong correlation with MR in delineating uterus, cervix, and
      central disease for 3D conformal intracavitary brachytherapy planning.

PMID- 21885141
TI  - Expression of Wnt-1, TGF-beta and related cell-cell adhesion components following
      radiotherapy in salivary glands of patients with manifested radiogenic
      xerostomia.
AB  - BACKGROUND: Radiation-induced xerostomia still represents a common symptom
      following radiotherapy of head and neck malignancies, which significantly impairs
      the patient's quality of life. In this cross-sectional study, human salivary
      glands were investigated to assess the role of Wnt/beta-catenin and TGF-beta
      pathways in the pathogenic process of radiogenic impairment of salivary function.
      METHODS: Irradiated human salivary glands were investigated in patients with
      manifested xerostomia. Alteration of Wnt-1 and cell-cell adhesion was evaluated
      immunohistologically as well as changes in the expression of TGF-beta were
      assessed in salivary gland tissue. RESULTS: We assessed two alteration patterns
      in which Wnt-1 expression represents one change along with up-regulation of beta
      catenin and E-cadherin in irradiated but viable acinar cells. Increased
      expression of tenascin-C was observed in sites of epithelial-mesenchymal
      interaction and loss of cell-cell adhesion was assessed in translocated
      epithelial cells in the stroma. CONCLUSION: Increased transdifferentiation and
      remodeling of acinar structures was associated with decrease of viable acinar
      structures. The role of Wnt and TGF signaling may provide a potential therapeutic
      approach to prevent radiation-induced damage to salivary glands during
      radiotherapy for head and neck cancer.

PMID- 21885142
TI  - Repeated cycles of peptide receptor radionuclide therapy (PRRT)--results and side
      effects of the radioisotope 90Y-DOTA TATE, 177Lu-DOTA TATE or 90Y/177Lu-DOTA TATE
      therapy in patients with disseminated NET.
AB  - PURPOSE: PRRT is a known tool in the management of patients with disseminated and
      inoperable NETs. The aim of study was to assess the effectiveness of the repeated
      cycles of PRRT in patients with disseminated and inoperable NETs. MATERIAL AND
      METHODS: Eighty nine patients were included in the PRRT. Among them 16 patients
      (18%) were qualified for a repeated PRRT cycle due to progression of the disease.
      In one of the patients qualified for the repeated cycle, PRRT was used as
      neoadjuvant therapy. The results and side-effects of the repeated cycles of PRRT
      were analyzed. RESULTS: Disease stabilization was observed in 10 patients 6
      months after the repeated PRRT cycle and in 5 patients after 12 and 18 months.
      Ten of the patients who had received repeated PRRT cycles died. In the case of
      neoadjuvant therapy, further reduction of the tumor size was observed, enabling
      qualification for surgery. Clinically significant reduction in the mean values of
      morphological parameters was not observed. Only after 12 and 18 months the mean
      values of creatinine levels were higher than the normal range (only in 2
      patients). CONCLUSIONS: The repeated cycles of PRRT did not cause a clinically
      significant increase of the toxicity of PRRT. The changes in kidney and blood
      morphology parameters were transient. The repeated cycles of PRRT enabled
      stabilization of the disease.

PMID- 21885143
TI  - 18F-FDG-PET imaging in radiotherapy tumor volume delineation in treatment of head
      and neck cancer.
AB  - PURPOSE: To determine the impact of (18)F-fluorodeoxyglucose positron emission
      tomography (PET) in radiotherapy target delineation and patient management for
      head and neck squamous cell carcinoma (HNSCC) compared to computed tomography
      (CT) alone. MATERIALS AND METHODS: Twenty-nine patients with HNSCC were included.
      CT and PET/CT obtained for treatment planning purposes were reviewed respectively
      by a neuroradiologist and a nuclear medicine specialist who were blinded to the
      findings from each other. The attending radiation oncologist together with the
      neuroradiologist initially defined all gross tumor volume of the primary (GTVp)
      and the suspicious lymph nodes (GTVn) on CT. Subsequently, the same radiation
      oncologist and the nuclear medicine specialist defined the GTVp and GTVn on (18)F
      FDG-PET/CT. Upon disagreement between CT and (18)F-FDG-PET on the status of a
      particular lymph node, an ultrasound-guided fine needle aspiration was performed.
      Volumes based on CT and (18)F-FDG-PET were compared with a paired Student's t
      test. RESULTS: For the primary disease, four patients had previous diagnostic
      tonsillectomy and therefore, FDG uptake occurred in 25 patients. For these
      patients, GTVp contoured on (18)F-FDG-PET (GTVp-PET) were smaller than the GTVp
      contoured on CT (GTVp-CT) in 80% of the cases, leading to a statistically
      significant volume difference (p=0.001). Of the 60 lymph nodes suspicious on PET,
      55 were also detected on CT. No volume change was observed (p=0.08). Ten biopsies
      were performed for lymph nodes that were discordant between modalities and all
      were of benign histology. Distant metastases were found in two patients and one
      had a newly diagnosed lung adenocarcinoma. CONCLUSIONS: GTVp-CT was significantly
      larger when compared to GTVp-PET. No such change was observed for the lymph
      nodes. (18)F-FDG-PET modified treatment management in three patients, including
      two for which no curative radiotherapy was attempted. Larger multicenter studies
      are needed to ascertain whether combined (18)F-FDG-PET/CT in target delineation
      can influence the main clinical outcomes.

PMID- 21885144
TI  - Monitoring tumor motion by real time 2D/3D registration during radiotherapy.
AB  - BACKGROUND AND PURPOSE: In this paper, we investigate the possibility to use X
      ray based real time 2D/3D registration for non-invasive tumor motion monitoring
      during radiotherapy. MATERIALS AND METHODS: The 2D/3D registration scheme is
      implemented using general purpose computation on graphics hardware (GPGPU)
      programming techniques and several algorithmic refinements in the registration
      process. Validation is conducted off-line using a phantom and five clinical
      patient data sets. The registration is performed on a region of interest (ROI)
      centered around the planned target volume (PTV). RESULTS: The phantom motion is
      measured with an rms error of 2.56 mm. For the patient data sets, a sinusoidal
      movement that clearly correlates to the breathing cycle is shown. Videos show a
      good match between X-ray and digitally reconstructed radiographs (DRR)
      displacement. Mean registration time is 0.5 s. CONCLUSIONS: We have demonstrated
      that real-time organ motion monitoring using image based markerless registration
      is feasible.

PMID- 21885145
TI  - Serial assessment of FDG-PET FDG uptake and functional volume during radiotherapy
      (RT) in patients with non-small cell lung cancer (NSCLC).
AB  - OBJECTIVES: The objectives were (i) to confirm that diagnostic FDG-PET images
      could be obtained during thoracic radiotherapy, (ii) to verify that significant
      changes in FDG uptake or volume could be measured early enough to adapt the
      radiotherapy plan and (iii) to determine an optimal time window during the
      radiotherapy course to acquire a single FDG-PET examination that would be
      representative of tumour response. METHODS: Ten non-small cell lung carcinoma
      (NSCLC) patients with significant PET/CT-FDG tumour radioactivity uptake (versus
      the background level), candidates for curative radiotherapy (RT, n=4; 60-70 Gy, 2
      Gray per fraction, 5 fractions per week) or RT plus chemotherapy (CT-RT, n=6),
      were prospectively evaluated. Using a Siemens Biograph, 5 or 6 PET/CT scans
      (PET(n), n=0-5) were performed for each patient. Each acquisition included a 15
      min thoracic PET with respiratory gating (RG) 60+/-5 min post-injection of the
      FDG (3.5 MBq/kg), followed by a standard, 5-min non-gated (STD) thoracic PET.
      PET(0) was performed before the first RT fraction. During RT, PET(1-5) were
      performed every 7 fractions, i.e., at 14 Gy total dose increment. FDG uptake was
      measured as the variation of SUV(max,PETn) versus SUV(max,PET0). Each lesions'
      volume was measured by (i) visual delineation by an experienced nuclear
      physician, (ii) 40% SUV(max) fixed threshold and (iii) a semi-automatic adaptive
      threshold method. RESULTS: A total of 53 FDG-PET scans were acquired. Seventeen
      lesions (6 tumours and 11 nodes) were visible on PET(0) in the 10 patients. The
      lesions were located either in or near the mediastinum or in the apex, without
      significant respiratory displacements at visual inspection of the gated images.
      Healthy lung did not cause motion artefacts in the PET images. As measured on 89
      lesions, both the absolute and relative SUV(max) values decreased as the RT dose
      increased. A 50% SUV(max) decrease was obtained around a total dose of 45 Gy. Out
      of the 89 lesions, 75 remained visually identifiable during the entire course of
      treatment. The 40% fixed threshold and adaptive threshold methods failed to
      delineate otherwise visible lesions in 16/33 (48%) and 3/33 (9%) lesions,
      respectively. The failure rate increased with increasing RT doses. Restricting
      the analysis to the manually-defined volumes in 89 visible lesions, the relative
      volumes decreased with increased dose. CONCLUSIONS: FDG-PET images can be
      analysed during thoracic RT, given either alone or with chemotherapy, without
      disturbing radiation-induced artefacts. An average 50% decrease in SUV(max) was
      observed around 40-45 Gy (i.e., during week 5 of RT). The three delineation
      methods yielded consistent volume measurements before RT and during the first
      week of RT, while manual delineation appeared to be more reliable later on during
      RT.

PMID- 21885146
TI  - Modeling germination of fungal spores at constant and fluctuating temperature
      conditions.
AB  - The germination of Penicillium expansum and Aspergillus niger spores was
      monitored microscopically on malt extract agar at isothermal conditions ranging
      from 0 to 33 degrees C and 5 to 41.5 degrees C, respectively. The obtained
      germination data, expressed as percentage of germination (% P) versus time, were
      fitted to the modified Gompertz equation for the estimation of the germination
      kinetic parameters (lag time, lambda(g), and germination rate, MU(g)), which were
      further modeled as a function of temperature via the use of Cardinal Models with
      Inflection (CMI). The effect of temperature on these parameters was similar with
      that previously reported for mycelium growth kinetics of the tested isolates. The
      germination of spores was also studied at various dynamic time-temperature
      conditions including single or sequential temperature shifts. The germination of
      spores at fluctuating temperatures was predicted using the modified Gompertz
      equation in conjunction with the CMI models for lambda(g) and MU(g) and based on
      the assumptions that i) a temperature shift does not result in any additional
      lambda(g) and, thus, the total lag can be calculated by adding relative parts of
      the lag time, and ii) after a temperature shift the germination rate MU(g) adapts
      instantaneously to the new temperature. The comparison between predicted and
      observed data showed that the germination of spores is strongly affected by the
      extent of the temperature shift, the percentage of germinated spores at the time
      of the shift and the fungal species. Apart from the scientific interest in
      understanding the dynamics of spores' germination, the models developed in this
      study can be used as tools in effective quality management systems for fungi
      control in foods.

PMID- 21885147
TI  - Transforming growth factor beta1 T868C gene polymorphism is associated with
      cerebral infarction in Japanese patients with type 2 diabetes.
AB  - It is likely that the C allele of the polymorphism at position 29 of the
      translated sequence of transforming growth factor (TGF)-beta1 gene, which codes a
      pleiotropic cytokine expressed in a variety of cells, is a susceptibility allele
      for cerebral infarction in Japanese type 2 diabetic patients.

PMID- 21885148
TI  - Protein oxidation markers in women with and without gestational diabetes
      mellitus: a possible relation with paraoxonase activity.
AB  - AIMS: To clarify the levels of protein oxidation markers such as protein carbonyl
      (PCO), protein hydroperoxides (P-OOH), advanced oxidation protein products (AOPP)
      and nitrotyrosine (NT), as well as antioxidative enzymes such as paraoxonase (PON
      1) in women with and without gestational diabetes mellitus (GDM). METHODS: The
      study was conducted on 23 women with GDM and 22 women without GDM. The levels of
      the P-OOH, AOPP, and PON-1 were determined by colorimetric methods; whereas NT
      and PCO levels were measured by ELISA. RESULTS: The concentrations of protein
      oxidation markers were significantly increased and PON1 activity was
      significantly decreased in GDM group compared to those of normal pregnant women.
      The control group showed a significant negative correlation between PON-1 and PCO
      (r=-0.451, p=0.027); whereas in GDM group, there was a significant positive
      correlation between P-OOH and HbA1c (r=0.89, p=0.001). There was no significant
      correlation between AOPP, PON-1, P-OOH, PCO, and HbA1c in either group.
      CONCLUSIONS: There is evidence of a possible association between protein
      oxidation and decreased PON1 activity in GDM. The increase in protein oxidation
      parameters in the GDM group leading to decreased PON1 activity might, we think,
      create a predisposition for clinical complications in GDM group.

PMID- 21885149
TI  - Pioneer factors: directing transcriptional regulators within the chromatin
      environment.
AB  - Chromatin is a well-known obstacle to transcription as it controls DNA
      accessibility, which directly impacts the recruitment of the transcriptional
      machinery. The recent burst of functional genomic studies provides new clues as
      to how transcriptional competency is regulated in this context. In this review,
      we discuss how these studies have shed light on a specialized subset of
      transcription factors, defined as pioneer factors, which direct recruitment of
      downstream transcription factors to establish lineage-specific transcriptional
      programs. In particular, we present evidence of an interplay between pioneer
      factors and the epigenome that could be central to this process. Finally, we
      discuss how pioneer factors, whose expression and function are altered in tumors,
      are also being considered for their prognostic value and should therefore be
      regarded as potential therapeutic targets. Thus, pioneer factors emerge as key
      players that connect the epigenome and transcription in health and disease.

PMID- 21885150
TI  - First pilot trial of the STAR-Liege protocol for tight glycemic control in
      critically ill patients.
AB  - Tight glycemic control (TGC) has shown benefits in ICU patients, but been
      difficult to achieve consistently due to inter- and intra- patient variability
      that requires more adaptive, patient-specific solutions. STAR (Stochastic
      TARgeted) is a flexible model-based TGC framework accounting for patient
      variability with a stochastically derived maximum 5% risk of blood glucose (BG)
      below 72 mg/dL. This research describes the first clinical pilot trial of the
      STAR approach and the post-trial analysis of the models and methods that underpin
      the protocol. The STAR framework works with clinically specified targets and
      intervention guidelines. The clinically specified glycemic target was 125 mg/dL.
      Each trial was 24 h with BG measured 1-2 hourly. Two-hourly measurement was used
      when BG was between 110-135 mg/dL for 3 h. In the STAR approach, each
      intervention leads to a predicted BG level and outcome range (5-95th percentile)
      based on a stochastic model of metabolic patient variability. Carbohydrate intake
      (all sources) was monitored, but not changed from clinical settings except to
      prevent BG<100 mg/dL when no insulin was given. Insulin infusion rates were
      limited (6 U/h maximum), with limited increases based on current infusion rate
      (0.5-2.0 U/h), making this use of the STAR framework an insulin-only TGC
      approach. Approval was granted by the Ethics Committee of the Medical Faculty of
      the University of Liege (Liege, Belgium). Nine patient trials were undertaken
      after obtaining informed consent. There were 205 measurements over all 9 trials.
      Median [IQR] per-patient results were: BG: 138.5 [130.6-146.0]mg/dL; carbohydrate
      administered: 2-11 g/h; median insulin:1.3 [0.9-2.4]U/h with a maximum of 6.0
      [4.7-6.0]U/h. Median [IQR] time in the desired 110-140 mg/dL band was: 50.0 [31.2
      54.2]%. Median model prediction errors ranged: 10-18%, with larger errors due to
      small meals and other clinical events. The minimum BG was 63 mg/dL and no other
      measurement was below 72 mg/dL, so only 1 measurement (0.5%) was below the 5%
      guaranteed minimum risk level. Post-trial analysis showed that patients were more
      variable than predicted by the stochastic model used for control, resulting in
      some of the prediction errors seen. Analysis and (validated) virtual trial re
      simulating the clinical trial using stochastic models relevant to the patient's
      particular day of ICU stay were seen to be more accurate in capturing the
      observed variability. This analysis indicated that equivalent control and safety
      could be obtained with similar or lower glycemic variability in control using
      more specific stochastic models. STAR effectively controlled all patients to
      target. Observed patient variability in response to insulin and thus prediction
      errors were higher than expected, likely due to the recent insult of cardiac
      surgery or a major cardiac event, and their immediate recovery. STAR effectively
      managed this variability with no hypoglycemia. Improved stochastic models will be
      used to prospectively test these outcomes in further ongoing clinical pilot
      trials in this and other units.

PMID- 21885151
TI  - Predictive markers in the adjuvant therapy of non-small cell lung cancer.
AB  - Adjuvant chemotherapy increases the 5-year survival rate of patients with
      completely resected non-small cell lung cancer (NSCLC) by absolute 5%. Molecular
      targeted therapies and predictive biomarkers to select those patients who benefit
      hold promise to further improve the outcome. Several biomarkers including ERCC1,
      BRCA1, EGFR, or gene signatures have been characterized in retrospective analyses
      of adjuvant therapy trials. However, differences in trial design and laboratory
      tests might have affected the outcome and might explain discordant results. With
      regard to many biomarkers, laboratory tests for their assessment remain to be
      standardized. After standardization of these tests and further validation
      studies, biomarkers might allow individualizing adjuvant treatment in patients
      with completely resected NSCLC in the future.

PMID- 21885152
TI  - Using constant head step tests to determine hydraulic apertures in fractured
      rock.
AB  - The initial step in the analysis of contaminant transport in fractured rock
      requires the consideration of groundwater velocity. Practical methods for
      estimating the average linear groundwater velocity (v-) in fractured rock require
      determination of hydraulic apertures which are commonly calculated by applying
      the cubic law using transmissivity (T) values and the number of hydraulically
      active fractures in the test interval. High-resolution, constant-head step
      injection testing of cored boreholes in a 100 m thick fractured dolostone aquifer
      was conducted using inflatable packers to isolate specific test intervals from
      the rest of the borehole. The steps in each test interval were gradually
      increased from very low to much higher injection rates. At smaller injection
      rates, the flow rate vs. applied pressure graph projects through the origin and
      indicates Darcian flow; non Darcian flow is evident at higher injection rates.
      Non-Darcian flow results in significantly lower calculated T values, which
      translates to smaller hydraulic aperture values. Further error in the calculated
      hydraulic aperture stems from uncertainty in the number of hydraulically active
      fractures in each test interval. This estimate can be inferred from borehole
      image and core logs, however, all of the fractures identified are not necessarily
      hydraulically active. This study proposes a method based on Reynolds number
      calculations aimed at improving confidence in the selection of the number of
      active fractures in each test interval.

PMID- 21885153
TI  - Defining the anatomical localisation of subsets of the murine mononuclear
      phagocyte system using integrin alpha X (Itgax, CD11c) and colony stimulating
      factor 1 receptor (Csf1r, CD115) expression fails to discriminate dendritic cells
      from macrophages.
AB  - The murine mononuclear phagocyte (MNP) system comprises a diverse population of
      cells, including monocytes, dendritic cells (DC) and macrophages. Derived from
      the myeloid haematopoietic lineage, this group of cells express a variety of well
      characterized surface markers. Expression of the integrin alpha X (Itgax, CD11c)
      is commonly used to identify classical DC, and similarly expression of colony
      stimulating factor 1 receptor (Csf1r, CD115) to identify macrophages. We have
      characterized the expression of these markers using a variety of transgenic mouse
      models. We confirmed previous observations of Itgax expression in anatomically
      defined subsets of MNPs in secondary lymphoid organs, including all MNPs
      identified within the germinal centres. The majority of MNPs in the intestinal
      lamina propria and lung express Itgax. All mucosal Itgax expressing cells also
      express Csf1r suggesting Csf1-dependent haematopoietic derivation. This double
      positive population included germinal centre MNPs. These data reveal that Itgax
      expression alone does not specifically define classical DC. These results suggest
      more cautious interpretation of Itgax-dependent experimentation and direct
      equation with uniquely DC-mediated activities, particularly in the functioning of
      non-lymphoid MNPs within the intestinal lamina propria.

PMID- 21885154
TI  - [Metronidazole: alternative treatment for ocular and cutaneous rosacea in the
      pediatric population].
AB  - OBJECTIVE: To assess the effectiveness and tolerance of systemic metronidazole in
      the treatment of childhood ocular and cutaneous rosacea. METHOD: Single-center
      multidisciplinary retrospective study. PATIENTS: Children aged between 1 and 15,
      with ocular and/or cutaneous rosacea, treated in the pediatric ophthalmology and
      dermatology department of Bordeaux, France, from January 1996 to September 2009.
      RESULTS: Eleven patients out of 20 had ocular and cutaneous rosacea, three had
      ocular symptoms only, and six had cutaneous symptoms only. In 11 patients (55%),
      the ocular symptoms preceded the skin disease. Meibomian cyst and phlyctenular
      conjunctivitis were the main symptoms. Keratitis was seen in four patients and
      lower corneal ulcer in two cases. The papulopustular form was the most frequent
      dermatologic form. All patients with ocular involvement received first-line
      treatment of eyelid hygiene. No topical ophthalmic treatment such as
      corticosteroid or cyclosporine 0.5% or 2% was used. Thirteen patients who showed
      no improvement despite eyelid treatment, the association of ocular and cutaneous
      rosacea, severe ocular involvement with keratitis, and severe recurrent cutaneous
      rosacea were treated orally. Two patients, aged between 12 and 14 years, received
      treatment with an anti-inflammatory dose of doxycycline for 2 to 3 months and
      achieved complete remission. One 22-month-old patient received oral treatment
      with erythromycin at a dose of 250 mg three times daily for 4 months. Ten
      patients, aged 12 to 64 months, were treated with systemic Metronidazole.
      Treatment lasting at least 3 months at a dose between 20 and 30 mg/kg per day was
      necessary to obtain complete and lasting remission. An early cessation of
      treatment, before 3 months, seems associated with partial remission of the
      disease and early recurrence. In cases complicated by ocular keratitis and
      corneal ulcer, prolonged treatment lasting 6 months led to clinical remission.
      The short courses (3-6 months) were preferred to long-term administration to
      prevent neurological toxicity. Maintenance therapy was based on eyelid hygiene.
      No recurrences and no toxic effects were observed at a median of 48 +/- 6 months.
      CONCLUSION: Childhood ocular rosacea is not rare, but is often misdiagnosed. It
      often precedes skin symptoms but it can remain isolated. Metronidazole could be
      alternative treatment for ocular and cutaneous rosacea in the pediatric
      population.

PMID- 21885155
TI  - Results of patch testing in 10 patients with peristomal dermatitis.
AB  - BACKGROUND: Peristomal dermatitis is a common problem in patients with ostomies
      that is a source of considerable morbidity. Irritant contact dermatitis is most
      common, but allergic contact dermatitis can also occur. Because of the lack of
      published reports on patch testing for this indication, we undertook a
      retrospective study of patch testing results in patients with suspected
      peristomal allergic contact dermatitis. OBJECTIVE: We sought to describe our
      patch testing experience with patients referred with peristomal dermatitis.
      METHODS: This was a retrospective review of medical records of patients with
      ostomies and peristomal dermatitis who underwent patch testing in the Mayo Clinic
      Departments of Dermatology in Jacksonville, FL; Rochester, MN; and Scottsdale,
      AZ, during a 10-year period (2000-2010). RESULTS: Ten patients with peristomal
      dermatitis were referred for patch testing (6 in Minnesota, 2 in Florida, and 2
      in Arizona). Patients were patch tested to the materials used in their stoma
      devices, to the standard series, and in some cases to supplemental series. All 10
      had at least one allergic patch test reaction, most commonly to stoma paste (3 of
      10 patients). LIMITATIONS: Retrospective nature of study via chart review is a
      limitation. CONCLUSION: Patch testing is a useful tool for identification of
      allergens in patients with peristomal dermatitis.

PMID- 21885156
TI  - Development of a clinical prediction rule for 30-day cardiac events in emergency
      department patients with chest pain and possible acute coronary syndrome.
AB  - STUDY OBJECTIVE: Evaluation of emergency department (ED) patients with chest pain
      who are at low risk for acute coronary syndrome is resource intensive and may
      lead to false-positive test results and unnecessary downstream procedures. We
      seek to identify patients at low short-term risk for a cardiac event for whom
      additional ED investigations might be unnecessary. METHODS: We prospectively
      enrolled patients older than 24 years and with a primary complaint of chest pain
      from 3 academic EDs. Physicians completed standardized data collection forms
      before diagnostic testing. The primary adjudicated outcome was acute myocardial
      infarction, revascularization, or death of cardiac or unknown cause within 30
      days. We used recursive partitioning to derive the rule and validated the model
      with 5,000 bootstrap replications. RESULTS: Of 2,718 patients enrolled, 336 (12%)
      experienced a cardiac event within 30 days (6% acute myocardial infarction, 10%
      revascularization, 0.2% death). We developed a rule consisting of the absence of
      5 predictors: ischemic ECG changes not known to be old, history of coronary
      artery disease, pain typical for acute coronary syndrome, initial or 6-hour
      troponin level greater than the 99th percentile, and age greater than 50 years.
      Patients aged 40 years or younger required only a single troponin evaluation. The
      rule was 100% sensitive (95% confidence interval 97.2% to 100.0%) and 20.9%
      specific (95% confidence interval 16.9% to 24.9%) for a cardiac event within 30
      days. CONCLUSION: This clinical prediction rule identifies ED chest pain patients
      at very low risk for a cardiac event who may be suitable for discharge. A
      prospective multicenter study is needed to validate the rule and determine its
      effect on practice.

PMID- 21885157
TI  - Epidemiologic surveillance of postoperative endophthalmitis in a specialized
      ophthalmologic center in Sao Paulo, Brazil.
AB  - This article describes a postoperative endophthalmitis (POE) surveillance system
      in place in a specialized ophthalmologic center in Sao Paulo, Brazil. The study
      involved a review of medical records from 2004-2009, during which a total of
      31,999 intraocular surgeries were performed. Nineteen of these cases fulfilled
      the criteria for POE, for an infection rate of 0.06%. The main etiologic agent
      causing POE was Pseudomonas aeruginosa, identified in 42.1% of the cases (8/19).

PMID- 21885158
TI  - Environmental factors associated with nosocomial legionellosis after anti-tumor
      necrosis factor therapy: case study.
AB  - In response to 2 reported cases of nosocomial legionellosis after anti-tumor
      necrosis factor (TNF) treatment, the environmental controls and testing
      facilities in a 221-bed acute care hospital were investigated. This investigation
      led to the implementation of a series of specific preventive measures adapted
      from protocols used to protect immunosuppressed patients. These 2 cases of
      legionellosis might be related to 2 concurrent events: treatment of hospitalized
      patients with anti-TNF drugs and secondary environmental changes related to major
      construction work. Patients undergoing anti-TNF treatment may be at increased
      risk for developing opportunistic infections during construction work,
      renovations, or water supply perturbations and require specific preventive
      measures.

PMID- 21885159
TI  - Severe cutaneous aspergillosis in a premature neonate linked to nonsterile
      disposable glove contamination?
AB  - After having eliminated a dysfunction of the hospital's ventilation system and
      any other possible environmental reservoir, the investigation of a fatal case of
      primary cutaneous aspergillosis in a neonate with extremely low birth weight led
      to the conclusion that nonsterile disposable gloves kept stored in their native
      packages were the likely source of contamination.

PMID- 21885160
TI  - Evaluation of the knowledge-sharing social network of hospital-based infection
      preventionists in Kentucky.
AB  - BACKGROUND: The role of the infection preventionist (IP) has become increasingly
      complex, underscoring the need for rapid mechanisms of knowledge acquisition. One
      mechanism for knowledge acquisition is knowledge-sharing through social networks.
      In a state such as Kentucky with predominantly rural health care facilities, an
      optimal knowledge-sharing network is critical; however, descriptions of these
      networks are absent from the literature. The objective of this study was to
      evaluate the knowledge-sharing networks of hospital-based IPs in Kentucky.
      METHODS: A survey was sent to all hospital-based IPs in Kentucky in November
      2010. Density and component analyses were used to evaluate network cohesion, and
      centrality statistics and key player algorithms were used to identify IPs
      important to the network. RESULTS: A total of 75 (58%) IPs completed the survey.
      The network density was 1.8%. Three components were identified. The median
      (range) centrality measures were as follows: in-degree, 2 (0-11); out-degree, 0.5
      (0-5); betweenness, 0 (0-567); and eigenvector 0.02 (0-0.45). Three key players
      were identified. CONCLUSIONS: Low network statistics indicate that the knowledge
      sharing network of hospital-based IPs might not be adequate for efficient
      knowledge-sharing. Interventions to increase the density of the network and
      reduce the number of components are needed.

PMID- 21885161
TI  - [Endoscopic image of a gastric duplication].

PMID- 21885162
TI  - [Diagnostic performance of colonoscopy in lower gastrointestinal bleeding].
AB  - Lower gastrointestinal bleeding is a common medical emergency that usually has a
      favorable prognosis. However, these events generate high resource use. The
      procedure of choice is colonoscopy with prior colonic preparation due to its high
      diagnostic performance and safety and the possibility of endoscopic therapy.
      Emergency colonoscopy has advantages over elective colonoscopy, showing higher
      diagnostic yield and superior detection of stigmata of recent bleeding,
      increasing the probability of endoscopic treatment. Predictive models of bleeding
      severity and recurrence have been published, allowing resource use to be
      rationalized, mainly by reducing hospital stay in low-risk patients.
      Nevertheless, the optimal timing of emergency colonoscopy has not been
      established and the impact of endoscopic treatment on prognosis is controversial.

PMID- 21885163
TI  - [Relationship between social support and blood glucose control in type 2 diabetes
      mellitus patients].

PMID- 21885164
TI  - [Clinical importance of the clopidogrel - omeprazole interaction: a question to
      solve].

PMID- 21885165
TI  - Anti-cancer activity of a novel palladium(II) complex on human breast cancer
      cells in vitro and in vivo.
AB  - Anti-cancer effects of a newly-synthesized palladium(II) complex,
      [Pd(sac)(terpy)](sac).4H(2)O (sac = saccharinate, and terpy = 2,2':6',2''
      terpyridine), were tested against human breast cancer cell lines, MCF-7 and MDA
      MB-231. The Pd complex had a strong anti-growth effect in a dose- and time
      dependent manner in vitro. This effect was also confirmed by the experiment
      performed on Balb/c mice in vivo. The IC(50) values were 0.09 MUM for MDA-MB-231
      and 3.05 MUM for MCF-7. It was also very effective in disrupting the formation of
      MDA-MB-231 tubules on matrigel, indicative of a putative anti-invasive activity.
      It induced apoptosis via the cell death genes of DR4 and DR5. In conclusion, this
      newly-synthesized Pd (II) complex represents a potentially active novel drug for
      the breast cancer treatment.

PMID- 21885166
TI  - Optically active 1,3,4,4-tetrasubstituted beta-lactams: synthesis and evaluation
      as tumor cell growth inhibitors.
AB  - The in vitro cytotoxicity assays of several enantiopure (3S,4S)- and (3R,4R)
      1,3,4,4-tetrasubstituted beta-lactams derived from amino acids have shown that
      the (3S,4S)-4-benzyl-1-p-methoxybenzyl-3-methyl-4-methoxycarbonyl derivative 2a,
      obtained from Phe, displays significant activity, which is comparable to that of
      the anticancer drug Doxorubicin against HT29 cell lines. Modifications at
      positions 1 and 4 of the beta-lactam ring led to identify the Tyr(2,6-ClBz)
      analogu 26d with similar activity data to those of 2a. The synthesis and SAR of
      all these tetrasubstituted beta-lactams are reported here.

PMID- 21885167
TI  - Novel indole and azaindole (pyrrolopyridine) cannabinoid (CB) receptor agonists:
      design, synthesis, structure-activity relationships, physicochemical properties
      and biological activity.
AB  - The discovery, synthesis and structure-activity relationship (SAR) of a novel
      series of cannabinoid 1 (CB(1)) and cannabinoid 2 (CB(2)) receptor ligands are
      reported. Based on the aminoalkylindole class of cannabinoid receptor agonists, a
      biphenyl moiety was introduced as novel lipophilic indole 3-acyl substituent in
      11-16. Furthermore, the 3-carbonyl tether was replaced with a carboxamide linker
      in 17-20 and the azaindole (pyrrolopyridine) nucleus was designed as indole
      bioisostere with improved physicochemical properties in 21-25. Through these SAR
      efforts, several high affinity CB(1)/CB(2) dual cannabinoid receptor ligands were
      identified. Indole-3-carboxamide 17 displayed single-digit nanomolar affinity and
      ~80 fold selectivity for CB(1) over the CB(2) receptor. The azaindoles displayed
      substantially improved physicochemical properties (lipophilicity; aqueous
      solubility). Azaindole 21 elicited potent cannabinoid activity. Cannabinoid
      receptor agonists 17 and 21 potently modulated excitatory synaptic transmission
      in an acute rat brain slice model of cannabinoid receptor-modulated
      neurotransmission.

PMID- 21885168
TI  - [Lung opacities].

PMID- 21885169
TI  - [Severe alcohol withdrawal syndrome (delirium tremens), at a crossroads between
      somatic and psychiatric components of alcoholic disorder].

PMID- 21885170
TI  - The value of involvement from the perspective of service users and carers engaged
      in practitioner education: not just a cash nexus.
AB  - This paper presents qualitative findings emergent from a participatory action
      research (PAR) study focused on developing service user and carer involvement in
      a university setting. The involvement of these experts by experience in
      practitioner education for health and social care, and nursing in particular, is
      now an international phenomenon. Adhering to the philosophy and practices of PAR,
      the project and the writing of this paper have been collectively produced. Data
      has been organised using simple thematic analysis into three broad themes
      accounting for different ways in which participating service users and carers
      obtain a sense of value from their involvement. We have titled these themes: a
      more positive sense of self; social and relational benefits; altruism in
      activism. Drawing on these participant narratives we develop an understanding of
      the relationship between involvement and reward that does not simply reflect
      value in payment.

PMID- 21885171
TI  - Ivan Illich on medical nemesis.

PMID- 21885172
TI  - Use of the masseter motor nerve in facial animation with free muscle transfer.
AB  - Facial paralysis is either congenital or acquired, and of varying severity, which
      leads to an asymmetrical or absent facial expression. It is an important
      disability both from the aesthetic and functional points of view. Between 2003
      and 2008, at the Department of Maxillofacial Surgery, University of Parma, Italy,
      21 patients with facial paralysis had their faces reanimated with a gracilis
      transplant reinnervated by the masseter motor nerve. All free-muscle transplants
      survived the transfer, and no flap was lost. Facial symmetry at rest and while
      smiling was excellent or good in most cases, and we found an appreciable
      improvement in both speech and oral competence. We consider that the masseter
      motor nerve is a powerful and reliable donor nerve, which allows us to obtain
      movement of the commissure and upper lip similar to those of the normal site for
      degree and direction. There may be a role for the masseter motor nerve in
      innervation of patients with facial paralysis.

PMID- 21885173
TI  - The effect of metal pollution on the population genetic structure of brown trout
      (Salmo trutta L.) residing in the River Hayle, Cornwall, UK.
AB  - The River Hayle in south-west England is impacted with metals and can be divided
      into three regions depending on the copper and zinc concentrations: a low-metal
      upper section; a highly-contaminated middle section and a moderately contaminated
      lower section. Hayle river water is toxic to metal-naive brown trout, but brown
      trout are found in the upper and lower regions. The study aimed to evaluate the
      population genetic structure of River Hayle brown trout and to determine if the
      highly-contaminated section acts as a chemical barrier to migration. Population
      genetic analysis indicated that metals were not a barrier to gene flow within the
      river, but there was a high level of differentiation observed between fish
      sampled at two sites in the upper region, despite being separated by only 1 km.
      The metal tolerance trait exhibited by this brown trout population may represent
      an important component of the species genetic diversity in this region.

PMID- 21885174
TI  - Paricalcitol versus ergocalciferol for secondary hyperparathyroidism in CKD
      stages 3 and 4: a randomized controlled trial.
AB  - BACKGROUND: The efficacy of 25-hydroxyvitamin D (25[OH]D) supplementation versus
      vitamin D receptor activators for the treatment of secondary hyperparathyroidism
      (SHPT) in patients with chronic kidney disease (CKD) stages 3 or 4 and vitamin D
      deficiency is unclear. STUDY DESIGN: Randomized controlled trial. SETTING &
      PARTICIPANTS: 80 patients with CKD stages 3 or 4, 25(OH)D level <30 ng/mL, and
      SHPT in a single medical center. INTERVENTION: Ergocalciferol, 50,000 units,
      titrated to achieve serum levels >=30 ng/mL versus paricalcitol, 1 or 2 MUg/d,
      for 16 weeks. OUTCOMES: The occurrence of 2 consecutive parathyroid hormone (PTH)
      levels decreased by at least 30% from baseline. All analyses were intention to
      treat. RESULTS: Baseline characteristics in the 2 groups were similar. 21
      patients (53%) on paricalcitol and 7 patients (18%) on ergocalciferol treatment
      achieved the primary outcome measure (P = 0.002). After 16 weeks, PTH levels did
      not decrease significantly in patients receiving ergocalciferol, but were
      decreased significantly in those treated with paricalcitol (mean estimate of
      between-group difference over 16 weeks of therapy, 43.9 pg/mL; 95% CI, 11.2-76.6;
      P = 0.009). Serum 25(OH)D levels increased significantly after 16 weeks in only
      the ergocalciferol group, but not the paricalcitol group (mean estimate of
      between-group difference over 16 weeks of therapy, 7.08 ng/mL; 95% CI, 4.32-9.85;
      P < 0.001). Episodes of hyperphosphatemia and hypercalcemia were not
      significantly different between the 2 groups. LIMITATIONS: Lack of blinding and
      use of surrogate end points. CONCLUSIONS: Paricalcitol is more effective than
      ergocalciferol at decreasing PTH levels in patients with CKD stages 3 or 4 with
      vitamin D deficiency and SHPT.

PMID- 21885175
TI  - Place effects for areas defined by administrative boundaries: a life course
      analysis of mortality and cause specific morbidity in Scania, Sweden.
AB  - To understand the origin of disease risk in adulthood, factors in all stages of
      life and on different contextual levels should be considered. Therefore, the aim
      of this study was to investigate the relevance of a person's area of residence
      over their life course with regard to four outcomes: all-cause mortality;
      ischemic heart disease mortality and morbidity; cancer mortality and morbidity;
      and respiratory diseases and related mortality. We applied a cross-classified
      multilevel model for three age groups on a longitudinal data set spanning a 35
      year period in Scania, Sweden. According to our analyses, the proportion of the
      total variance at the district level for all the outcomes studied was below 2%
      for the 65 to 84 age group, below 4.5% for those ages 50-64 years, and below 6.5%
      for those 30-49 years old. Our results suggest that the parish of residence, at
      four different time points during the individual life course, had little
      influence on individual all-cause mortality, or on mortality or morbidity from
      IHD, cancer, and respiratory diseases; i.e., knowing when and where an individual
      resided during their life course gives little indication of future mortality and
      morbidity. Such knowledge is essential in assisting decision makers determine the
      relevant geographical level of intervention (in our case whether to direct
      interventions toward the entire region of Scania or to specific parishes) needed.
      Valuable information for planning public health interventions might be obtained
      by considering measures of variance and clustering from specific contexts before
      implementing strategic programs.

PMID- 21885176
TI  - Attentional disengagement in adults with Williams syndrome.
AB  - Williams syndrome (WS) is a neurodevelopmental disorder characterized by a
      distinctive behavioral and cognitive profile, including widespread problems with
      attention. However, the specific nature of their attentional difficulties, such
      as inappropriate attentional allocation and/or poor attentional disengagement
      abilities, has yet to be elucidated. Furthermore, it is unknown if there is an
      underlying difficulty with the temporal dynamics of attention in WS or if their
      attentional difficulties are task-dependent, because previous studies have
      examined attention in established areas of deficit and atypicality (specifically,
      visuospatial and face processing). In this study, we examined attentional
      processing in 14 adults with WS (20-59 years) and 17 typically developing
      controls (19-39 years) using an attentional blink (AB) paradigm. The AB is the
      decreased ability to detect a second target when it is presented in close
      proximity to an initial target. Overall, adults with WS had an AB that was
      prolonged in duration, but no different in magnitude, compared with typically
      developing control participants. AB performance was not explained by IQ, working
      memory, or processing speed in either group. Thus, results suggest that the
      attention problems in WS are primarily due to general attentional disengagement
      difficulties rather than inappropriate attentional allocation.

PMID- 21885177
TI  - Examining age-related movement representations for sequential (fine-motor) finger
      movements.
AB  - Theory suggests that imagined and executed movement planning relies on internal
      models for action. Using a chronometry paradigm to compare the movement duration
      of imagined and executed movements, we tested children aged 7-11 years and adults
      on their ability to perform sequential finger movements. Underscoring this tactic
      was our desire to gain a better understanding of the age-related ability to
      create internal models for action requiring fine-motor movements. The task
      required number recognition and ordering and was presented in three levels of
      complexity. Results for movement duration indicated that 7-year-olds and adults
      were different from the other groups with no statistical distinction between 9-
      and 11-year-olds. Correlation analysis indicated a significant relationship
      between imagined and executed actions. These results are the first to document
      the increasing convergence between imagined and executed movements in the context
      of fine-motor behavior; a finding that adds to our understanding of action
      representation in children.

PMID- 21885178
TI  - Influence of response prepotency strength, general working memory resources, and
      specific working memory load on the ability to inhibit predominant responses: a
      comparison of young and elderly participants.
AB  - One conception of inhibitory functioning suggests that the ability to
      successfully inhibit a predominant response depends mainly on the strength of
      that response, the general functioning of working memory processes, and the
      working memory demand of the task (Roberts, Hager, & Heron, 1994). The proposal
      that inhibition and functional working memory capacity interact was assessed in
      the present study using two motor inhibition tasks (Go/No-Go and response
      incompatibility) in young and older participants. The strength of prepotency was
      assessed with a short or long training phase for the response to be inhibited.
      The influence of working memory resources was evaluated by administering the
      tasks in full vs. divided attention conditions. The effect of working memory load
      was manipulated by increasing the number of target and distracter items in each
      task. Results showed no effect of prepotency strength, whereas dividing
      attentional resources and increasing working memory load were associated with
      greater inhibitory effects in both groups and for both tasks. This deleterious
      effect was higher for older participants, except in the working memory load
      condition of the Go/No-Go task. These results suggest an interactive link between
      working memory and response inhibition by showing that taxing working memory
      resources increases the difficulty of inhibiting prepotent responses in younger
      and older subjects. The additional detrimental effect of these factors on healthy
      elderly subjects was related to their decreased cognitive resources and to their
      shorter span size.

PMID- 21885179
TI  - [Case report: squamous cell carcinoma, radial forearm flap and Huriez syndrome.
      Focus on a rare pathology].
AB  - Huriez disease is a rare autosomal dominant pathology characterized by the triad
      hypoplastic nail, hyperkeratosis and scleroatrophy of distal extremities. One of
      its most principal complications is the development of an aggressive squamous
      cell carcinoma. We present a case of a 62-year old patient who had an acute two
      hands scleroatrophy associated with recurrent squamous cell carcinoma treated by
      large excision and covered by trophic and thick radial forearm flap. This flap
      allowed us to treat the wound and the sclerosis shrinkage with aim to give back
      the functional benefit to the patient. It also gave the patient an oncological
      treatment despite aggressive management in one step surgery. Furthermore, one
      year later we did not observe cutaneous flap histological modification that could
      have degenerated into cancer. A multidisciplinary approach with dermatologists,
      geneticists and plastic surgeons is essential in addition with close medical
      supervision because of high cancer risks.

PMID- 21885181
TI  - Does azurin bind to the transactivation domain of p53? A Trp phosphorescence
      study.
AB  - The bacterial redox protein azurin has been shown to be able to enter into cancer
      cells and induce apoptosis by stabilizing p53. Although the formation of a
      complex between the two proteins has been demonstrated, little is known about
      their binding features. We investigated the interaction between the transcription
      activation domain of p53 (p53(1-63)) and Pseudomonas aeruginosa azurin using
      fluorescence and phosphorescence spectroscopic techniques. Trp phosphorescence
      lifetime measurements revealed conformational changes in azurin induced by the
      interaction with p53(1-63). Acrylamide quenching of Trp phosphorescence also
      indicated a significant increase in the overall flexibility of azurin upon
      binding to p53(1-63). We show that azurin binds to the N-terminal region of p53
      with a dissociation constant in the 5-10 MUM range. No change in the fluorescence
      and phosphorescence emission of p53(1-63) was detected in the presence of azurin.
      This result indicated that no Trp residue of p53(1-63) is located in the
      interaction site with azurin and therefore suggested that the azurin binding site
      does not overlap that of MDM2, the protein that plays a crucial role in the p53
      regulation. The present results may assist in the design of novel cancer
      treatments based on p53 stabilization by azurin.

PMID- 21885182
TI  - LESS is more ... but needs even more.

PMID- 21885180
TI  - [How beta-blockers are used in Spain? Analysis of limitations in their use in
      internal medicine and cardiology: CARACTER-BETA study].
AB  - INTRODUCTION AND OBJECTIVES: Beta-blocker treatment has a class I indication,
      level of evidence A, in guidelines for the treatment of heart failure, ischemic
      heart disease, and atrial fibrillation. However, beta-blocker use continues to be
      less than optimal. In this study, beta blocker use in Spain is analyzed in
      patients with heart failure, ischemic heart disease, and atrial fibrillation.
      METHODS: Observational, epidemiologic, cross-sectional, multicenter study
      including 1608 patients with heart failure, ischemic heart disease, and/or atrial
      fibrillation, recruited in 150 healthcare centers by cardiologists and internal
      medicine specialists. RESULTS: Cardiologists enrolled 78.6% patients and internal
      medicine specialists 21.4%; 25.8% were recruited at hospital discharge and 74.2%
      at outpatient centers. Men accounted for 77% of the sample, and age was 68 (12)
      years. Of the total, 73% had ischemic heart disease, 42% heart failure, and 36%
      atrial fibrillation (multiresponse variable). Beta blockers were given to 82.8%
      of those consulting in cardiology compared to 71.6% of those treated in internal
      medicine (P<.0001). By pathology, the prescription rate was 85.1% of patients
      with ischemic heart disease, 77.0% of those with heart failure, and 72.4% of
      those with atrial fibrillation. Cardiology prescribed significantly more beta
      blockers for ischemic heart disease and heart failure than did internal medicine.
      Multivariate analysis showed that beta blocker use increased when the patient had
      ischemic heart disease, was treated by a cardiologist, and had dyslipidemia,
      stroke, and/or left ventricular hypertrophy. beta blocker use decreased with age
      and with a history of bronchospasm, asthma, bradycardia, chronic obstructive
      pulmonary disease, and/or intermittent claudication. CONCLUSIONS: There is still
      room for improvement in beta blocker prescription in Spain for patients with
      ischemic heart disease, heart failure, and/or atrial fibrillation.

PMID- 21885183
TI  - Can we apply nomograms derived in the United States to European patients? Yes, we
      can!

PMID- 21885184
TI  - Prostate cancer units: has the time come to discuss this thorny issue and promote
      their establishment in Europe?

PMID- 21885185
TI  - Mixed split cord malformation: are we missing something?
AB  - BACKGROUND: The new classification for split cord malformation, based on the
      unified theory of embryogenesis includes two types Type I and II defined on the
      basis of the nature of the medium septum and the state of the dural tube.
      According to this, these are the only two essential features needed for typing
      and there is never an overlap between the two main forms. We have described two
      cases that defy this theory. CASE REPORT: We present two patients with split cord
      malformation who appear to have a combination of features specific to Type I and
      Type II. Both patients had a partial bony spur within a single dural sac.
      CONCLUSION: An overlap between the two forms of split cord malformation does
      exist. The role of meninx primitiva in the formation of median bony septum is
      debatable.

PMID- 21885186
TI  - Corticospinal tract dysfunction in a patient with acute motor axonal neuropathy
      (AMAN).

PMID- 21885187
TI  - The behavior and long-term fate of metals in simulated landfill bioreactors under
      aerobic and anaerobic conditions.
AB  - The long-term behavior and fate of metals in leachate from four simulated
      bioreactor landfills were explored using lysimeters under both aerobic and
      anaerobic conditions for a maximum of 1650 days. Metal concentrations varied with
      time and stage of landfill activity. The behavior of selected metals (Al, As, Cr,
      Cu, Fe, Pb, and Zn) significantly differed between aerobic and anaerobic
      conditions. Leachate from the aerobic lysimeters contained greater concentrations
      of Al, Cu, and Pb compared to leachate derived from the anaerobic lysimeters
      (average concentrations of Al, Cu and Pb in the aerobic/anaerobic lysimeters were
      8.47/0.78 mg/L, 1.61/0.04 mg/L and 0.10/0.03 mg/L, respectively). In the
      anaerobic lysimeters, As, Fe and Zn leached at greater concentrations (average
      concentrations of As, Fe and Zn in the aerobic/anaerobic lysimeters were
      0.40/1.14 mg/L, 13.5/136 mg/L and 15.3/168 mg/L, respectively). Though no
      significant difference in overall Cr concentrations was observed in leachate
      samples from aerobic and anaerobic lysimeters, during the alkali and methane
      phases approximately 45% of Cr was presented as Cr(VI) under aerobic conditions,
      whereas no Cr(VI) was detected under anaerobic conditions.

PMID- 21885188
TI  - Evidence for shifts in the structure and abundance of the microbial community in
      a long-term PCB-contaminated soil under bioremediation.
AB  - Although the impact of bioremediation of PCB-contaminated sites on the indigenous
      microbial community is a key question for soil restoration, it remains poorly
      understood. Therefore, a small-scale bioremediation assay made of (a) a
      biostimulation treatment with carvone, soya lecithin and xylose and (b) two
      bioaugmentation treatments, one with a TSZ7 mixed culture and another with a
      Rhodococcus sp. Z6 pure strain was set up. Changes in the structure of the global
      soil microbial community and in the abundances of different taxonomic phyla were
      monitored using ribosomal intergenic spacer analysis (RISA) and real-time PCR.
      After an 18-month treatment, the structure of the bacterial community in the
      bioremediated soils was significantly different from that of the native soil. The
      shift observed in the bacterial community structure using RISA analysis was in
      accordance with the monitored changes in the abundances of 11 targeted phyla and
      classes. Actinobacteria, Bacteriodetes and alpha- and gamma-Proteobacteria were
      more abundant under all three bioremediation treatments, with Actinobacteria
      representing the dominant phylum. Altogether, our results indicate that
      bioremediation of PCB-contaminated soil induces significant changes in the
      structure and abundance of the total microbial community, which must be addressed
      to implement bioremediation practices in order to restore soil functions.

PMID- 21885189
TI  - Structural characterisation of Arquad(r) 2HT-75 organobentonites: surface charge
      characteristics and environmental application.
AB  - Organoclays are increasingly being used to remediate both contaminated soils and
      waste water. The present study was attempted to elucidate the structural
      evolution of bentonite based organoclays prepared from a commercially available,
      low-cost alkyl ammonium surfactant Arquad((r)) 2HT-75. XRD, FTIR, SEM and zeta
      potential measurement were used to characterise the organoclays. In particular,
      the relationship between surface charge characteristics of the organoclays and
      their ability to remediate organic contaminants such as phenol and p-nitrophenol
      was investigated. The investigation revealed that the arrangement and
      conformation of surfactant molecules in the bentonite became more regular,
      ordered and solid-like as of Arquad((r)) 2HT-75 loading increased. This also led
      to the formation of a positive zeta potential on the surface of organobentonites
      prepared with 3.57:1 and 4.75:1 surfactant-clay (w/w) ratio. The zeta potential
      values decreased with increasing pH of the suspension. The adsorption data of
      phenol and p-nitrophenol were best fitted to Freundlich isotherm model. The
      adsorption was controlled by multiple mechanisms of partitioning, physico
      sorption and chemisorption. The outcomes of this study are useful for the
      synthesis of low cost organobentonite adsorbents for the remediation of ionisable
      organic contaminants such as phenol and p-nitrophenol from waste water.

PMID- 21885190
TI  - Ecotoxicological impacts of clofibric acid and diclofenac in common carp
      (Cyprinus carpio) fingerlings: hematological, biochemical, ionoregulatory and
      enzymological responses.
AB  - Investigation on the toxic effects of pharmaceutical drugs namely clofibric acid
      (CA) and diclofenac (DCF) were studied in a common carp Cyprinus carpio at
      different concentrations such as 1, 10 and 100 MUg L(-1) for a short-term period
      of 96 h under static bioassay method. At all concentrations, red blood cell
      (RBC), plasma sodium (Na(+)), potassium (K(+)), and glutamate oxaloacetate
      transaminase (GOT) levels were decreased in fish treated with CA and DCF.
      Contrastingly, white blood cell (WBC), plasma glucose, protein, lactate
      dehydrogenase (LDH) and gill Na(+)/K(+)-ATPase level were increased. However, a
      mixed trend was observed in hemoglobin (Hb), hematocrit (Hct), plasma chloride
      (Cl(-)), mean cellular volume (MCV), mean cellular hemoglobin (MCH), mean
      cellular hemoglobin concentration (MCHC) and glutamate pyruvate transaminase
      (GPT) levels. There was a significant (P<0.01 and P<0.05) change in all
      parameters measured in fish exposed to different concentrations of CA and DCF. In
      summary, the alterations in hematological, biochemical, ionoregulatory and
      enzymological parameters can be used as biomarkers in monitoring the toxicity of
      CA and DCF in aquatic environment. However, more detailed studies on using of
      specific biomarkers to monitor the human pharmaceuticals are needed.

PMID- 21885191
TI  - Tantalum (oxy)nitrides: preparation, characterisation and enhancement of photo
      Fenton-like degradation of atrazine under visible light.
AB  - Tantalum (oxy)nitrides were prepared by the nitridation of Ta(2)O(5) and were
      added to a photo-Fenton-like system to enhance Fe(3+) reduction and atrazine
      degradation under visible light. The samples were characterized by XRD, XPS, DRS
      and BET analyses. XPS analysis showed that the nitrogen content of the tantalum
      (oxy)nitride samples increased noticeably with the nitridation temperature and
      nitridation time but slightly with the flow rate of NH(3). XRD results showed
      Ta(2)O(5) was first converted to TaON and then to Ta(3)N(5) when the nitridation
      temperature increased. DRS analysis showed that the sample obtained at 800
      degrees C displayed the strongest absorption of visible light. However, the
      ability of the tantalum (oxy)nitrides to reduce Fe(3+) did not increase
      continuously with the nitrogen content. Sample 7 (700 degrees C, [Formula: see
      text] , 6h) showed the highest level of photocatalytic activity for Fe(3+)
      reduction. This is because the photocatalytic activity of TaON for Fe(3+)
      reduction is higher than that of Ta(3)N(5). And a slight synergetic effect was
      observed between TaON and Ta(3)N(5). With the addition of sample 7, H(2)O(2)
      decomposition and atrazine degradation were significantly accelerated in a photo
      Fenton-like system under visible light. The regenerated tantalum (oxy)nitrides
      catalyst displayed considerably stable performance for atrazine degradation.

PMID- 21885192
TI  - Recycle of electrolytically dissolved struvite as an alternative to enhance
      phosphate and nitrogen recovery from swine wastewater.
AB  - Operational parameters such as electric voltage, NaCl, reaction time (RT) and
      initial struvite amount were optimized for struvite dissolution with a designed
      electrolysis reactor, and the effect of recycling the dissolved solution on the
      performance of struvite crystallization was also assessed. The electrolytic
      reactor was made of plexiglas having titanium plate coated with iridium oxide as
      anode (surface area: 400 cm(2)) and stainless steel plates as cathodes. For
      reutilization of dissolved struvite, four runs were conducted with different
      recycle ratio of the solution. Optimum conditions for the electric voltage, NaCl,
      RT and initial struvite amount were 7 V, 0.06%, 1.5h and 1.25 g/L, respectively.
      At the above optimized conditions, 49.17 mg/L phosphate (PO(4)(3-)-P) was
      dissolved and ammonium-nitrogen (NH(4)-N) got completely removed from the
      solution. When 0.0, 0.5, 1.0 and 2.0 moles of the dissolved struvite with respect
      to PO(4)(3-)-P in swine wastewater were recycled along with 0.5M magnesium
      chloride (MgCl(2)), the PO(4)(3-)-P removal was 63, 69, 71 and 79%, and NH(4)-N
      was 9, 31, 40 and 53%, respectively. Hence, the performance of struvite formation
      process was proportionally increased. It is concluded that struvite can be re
      dissolved by electrolysis and reused as a source of P and Mg.

PMID- 21885193
TI  - The modern paradox of unregulated cooking activities and indoor air quality.
AB  - Pollutant emission from domestic and commercial cooking activities is a
      previously neglected area of concern with respect to human health worldwide. Its
      health effects are relevant to people across the globe, not only those using low
      quality food materials in lesser-developed countries but also to more affluent
      people enjoying higher quality food in developed countries. Based on the
      available database of pollutant emissions derived from fire-based cooking, its
      environmental significance is explored in a number of ways, especially with
      respect to the exposure to hazardous vapors and particulate pollutants.
      Discussion is extended to describe the risk in relation to cooking methods,
      cooking materials, fuels, etc. The observed pollutant levels are also evaluated
      against the current regulations and guidelines established in national and
      international legislation. The limitations and future prospects for the control
      of cooking hazards are discussed.

PMID- 21885194
TI  - Toluene and chlorobenzene dinitration over solid H3PO4/MoO3/SiO2 catalyst.
AB  - A new catalyst, H(3)PO(4)/MoO(3)/SiO(2), was prepared by modification of
      MoO(3)/SiO(2) using phosphoric acid. The characterization of the catalyst was
      performed using Infrared and Raman Spectroscopy, potentiometric titration and
      nitrogen adsorption-desorption methods. Molybdenum oxides were identified along
      with phosphomolybdic acid and polymolybdates on the modified surface. The
      suitability of the catalysts for toluene and chlorobenzene nitration in
      continuous process was examined. Toluene is effectively nitrated to
      dinitrotoluene (DNT) in one-stage process (96 wt.% of DNT in the product) and in
      mild conditions i.e. at room temperature and only with ten-fold excess of nitric
      acid. In chlorobenzene nitration only twelve-fold excess of nitric acid is needed
      to obtain as high yield as 95 wt.%. Most importantly, the novel catalysts we have
      developed, provide the opportunity for sulfuric acid- free nitration of aromatic
      compounds.

PMID- 21885195
TI  - Estimate of the optimum weight ratio in zero-valent iron/pumice granular mixtures
      used in permeable reactive barriers for the remediation of nickel contaminated
      groundwater.
AB  - This paper presents the results of laboratory column tests aimed at defining the
      optimum weight ratio of zero-valent iron (ZVI)/pumice granular mixtures to be
      used in permeable reactive barriers (PRBs) for the removal of nickel from
      contaminated groundwater. The tests were carried out feeding the columns with
      aqueous solutions of nickel nitrate at concentrations of 5 and 50 mg/l using
      three ZVI/pumice granular mixtures at various weight ratios (10/90, 30/70 and
      50/50), for a total of six column tests; two additional tests were carried out
      using ZVI alone. The most successful compromise between reactivity (higher ZVI
      content) and long-term hydraulic performance (higher Pumice content) seems to be
      given by the ZVI/pumice granular mixture with a 30/70 weight ratio.

PMID- 21885196
TI  - Prevalence of Giardia duodenalis assemblages in weaned cattle on cow-calf
      operations in the United States.
AB  - To determine the prevalence of Giardia duodenalis in weaned beef calves on cow
      calf operations in the United States, fecal specimens were collected from 819
      calves (6-18 months of age) from 49 operations. After cleaning and concentration
      procedures to maximize recovery of cysts from feces, DNA was extracted from each
      of the 819 specimens. The presence of G. duodenalis was determined by nested PCR
      of a fragment of the SSU rRNA gene. All positive PCR products were subjected to
      sequence analysis. The overall sample level prevalence of Giardia was 33.5% with
      prevalence ranging from 0 to 100% among operations. The highest within herd
      prevalence of infected beef calves was found in one cow-calf operation from the
      South region (100%), followed by a cow-calf operation from the West region (90%),
      and three cow-calf operations from the Midwest region (87.5, 85, and 85%).
      Giardia was not detected in samples from 7 operations including 5 cow-calf
      operations from the South region, and 1 cow-calf operation each from the Midwest
      and West regions. Molecular analysis of the Giardia-positive samples identified
      assemblage E (or E-like) in 31.7% of all samples (260/819) and assemblage A in
      1.2% (10/819). A mixed infection with assemblages A and E was observed in four
      calves from an operation in Midwest region. The potentially zoonotic assemblage A
      was detected in specimens from four operations in Midwest region. These findings
      indicate that most G. duodenalis found in weaned beef calves was assemblage E
      which represents no known zoonotic threat. However, the presence of assemblage A
      in a small number of animals poses a potential risk of infection to humans.

PMID- 21885197
TI  - Prevalence and characteristics of substance abuse treatment utilization by U.S.
      adolescents: national data from 1987 to 2008.
AB  - OBJECTIVE: Although many adolescents use and abuse illicit drugs, few of those
      who could benefit from substance abuse treatment ever receive these services. The
      present study examines the prevalence of utilization of substance abuse treatment
      in national samples of adolescents over the past 22 years and identifies
      characteristics associated with receipt of these services. METHOD: Monitoring the
      Future data on lifetime utilization of substance abuse treatment was available
      for 12th grade students who reported any lifetime illicit drug use from 1987 to
      2008 (N=25,537). After describing the prevalence of treatment utilization over
      this time period, logistic regression was used to examine potential predictors of
      treatment utilization. RESULTS: The overall prevalence of treatment utilization
      has remained relatively unchanged over the past 22 years. In multivariable
      models, adolescents reporting a greater frequency of lifetime use of marijuana or
      cocaine were more likely to receive substance abuse treatment. Additionally,
      substance abuse treatment utilization was more likely in those who received other
      mental health services. CONCLUSION: Despite increased evidence for the
      effectiveness of substance abuse treatment, utilization of these services by
      adolescents has remained low and relatively stable over the past 22 years.
      Attempts to increase utilization of substance abuse treatment services would
      likely benefit from building on existing connections with mental health
      treatment.

PMID- 21885198
TI  - Flexural-torsional buckling initiates idiopathic scoliosis.
AB  - Initiation of the spinal deformity in idiopathic scoliosis (IS) has been
      attributed to an abnormal pattern of spinal growth during development. However,
      recent findings suggest that the earliest observable event in the pathogenesis of
      IS is a change in the shape of intervertebral discs with alterations in the shape
      of vertebrae being considered a secondary event. Starting from the previous
      description of the spinal deformity in IS as 'buckling' of the spine a new
      hypothesis describing the initial spinal deformity in IS as flexural-torsional
      buckling, a three-dimensional type of failure of axially loaded columns, is
      proposed. According to the new hypothesis the initiating event (the earliest
      observable event) in IS is flexural-torsional buckling developing from the
      flexible parts (intervertebral discs and ligaments) of the affected spinal motion
      segments. Since flexural-torsional buckling occurs in columns with a cross
      section of one axis of symmetry characterised by a much greater in-plane than out
      of-plane bending stiffness the new hypothesis predicts that the initiating
      condition (the condition promoting the initiation) of IS is 'flexibility
      anisotropy' namely significantly higher bending stiffness in lateral bending than
      bending stiffness in flexion-extension of a part of the spine. The parameter of
      'flexibility anisotropy' as a factor for initiation of IS has never been
      suggested or tested before. The present hypothesis has implications in the
      research on the pathogenesis of IS as well as in the development of new methods
      for its treatment.

PMID- 21885199
TI  - Is rheumatoid arthritis a risk factor for oral bisphosphonate-induced
      osteonecrosis of the jaws?
AB  - Bisphosphonate-related osteonecrosis of the jaws is a relevant side-effect of
      these drugs that has been generating a great concern through increasing reports,
      worldwide, of this bone necrosis. Among several BRONJ hypothetical co-factors
      that could play a role in BRONJ pathogenesis, rheumatoid arthritis (RA) has been
      included as a relevant risk factor for BRONJ; however, until now the relationship
      between these diseases has not been fully explained. Thus, the purpose of this
      paper is to establish hypothetical factors that could link these two diseases,
      considering mainly inflammatory components and the organism effects of medicines
      used to treat RA, particularly steroids and methotrexate (MTX).

PMID- 21885200
TI  - Is high frequency yawning: a behavioural event of ethanol withdrawal.

PMID- 21885201
TI  - Secretion of bacterial chondroitinase ABC from bone marrow stromal cells by
      glycosylation site mutation: a promising approach for axon regeneration.
AB  - Growth-inhibitory chondroitin sulfate proteoglycans (CSPGs) contribute a lot to
      failure of axon regeneration. Chondroitinase ABC (ChABC) digests
      glycosaminoglycan chains attached in CSPGs and can thereby promote axonal
      regeneration beyond a lesion site. However, CSPGs expression are up-regulated for
      almost 7 weeks after spinal cord injury (SCI) in vivo, so single dose of
      exogenous ChABC is insufficient for long distance of axon sprout and functional
      recovery. It is considered an ideal strategy to transfect neurons and/or glia at
      the injury site with a vector containing the gene encoding chondroitinase, so
      they can secrete ChABC themselves. Mammalian cells in the current studies,
      however, can not secret ChABC efficiently. It is well established that
      glycosylation is a common obstacle for eukaryotic cells to secret bacterial
      protein. ChABC is a protein heavily glycosylated structurally, and it was
      reported that inhibiting the glycosylation of xylosyltransferase-1 with a DNA
      enzyme could reduce GAG chains in the lesion of spinal cord. So presence of
      glycosylation sites in the bacterial sequence is supposed the barrier that
      preventing ChABC secretion from mammalian cells. We intend to mutate the key N
      glycosylation sites of the bacterial ChABC sequence and transduce it into BMSCs
      by lentivirus vector. The modified BMSCs are expected to promote axon
      regeneration through multiple mechanisms, providing sustained ChABC and
      neurotrophic factors, as well as filling in the cavities formed post-trauma. The
      transduced BMSCs with gene mutated in key glycosylation sites in the present
      hypothesis provide a promising strategy to promote axon regeneration.

PMID- 21885202
TI  - Can rhabdomyolysis be a cause of sudden death in young athletes?

PMID- 21885203
TI  - Early add-on immunoglobulin administration in Rasmussen encephalitis: the
      hypothesis of neuroimmunomodulation.
AB  - Rasmussen encephalitis (RE) is a chronic inflammatory disease leading to
      unilateral hemispheric atrophy, associated with progressive neurological
      dysfunction and intractable seizures. The best approach to RE is hemispherectomy.
      However long-term immunotherapy seems to prevent or slow down hemispheric tissue
      loss and the associated functional decline. We describe a girl with epilepsia
      partialis continua (EPC) and progressive neurological dysfunction compatible with
      RE. The brain MRI showed a lesion that was initially interpreted as focal
      cortical dysplasia. Combined antiepileptic and immunomodulation were administered
      for two years with initial beneficial effects. The follow-up MRI, 4 year later
      showed. atrophic change in right parietal region. The association of
      antiepileptic and immunomodulation therapies may inhibit pathogenetic mechanisms
      responsible for neuronal loss in RE, slowing down the progression of the disease.

PMID- 21885204
TI  - Injectable allogeneic bone mesenchymal stem cells: a potential minimally invasive
      therapy for atrophic nonunion.
AB  - How to enhance atrophic nonunion repairing is a common challenge encountered in
      orthopaedic surgeons. With the increasing popularity of minimally invasive
      techniques, one of the major thrusts in treatment approaches for atrophic
      nonunions is to develop injectable systems that can shorten the surgical
      operation time, reduce the morbidity and costs for patients. Bone mesenchymal
      stem cells (BMSCs) may provide new strategies to treat atrophic nonunion because
      of their prolonged self-renewal capacity and ability to differentiate into
      osteogenic lineage under the proper conditions. However, providing an autologous
      BMSCs in the clinical setting is often limited, because the patient's marrow is
      damaged or the cell yield from healthy marrow is reduced. Due to the limitation
      of autologous BMSCs in clinical application, we turn to consider allogeneic BMSCs
      as seeding cells in atrophic nonunion repair. Allogeneic BMSCs could are isolated
      from one or more donors would have the potential to be expanded and cryopreserved
      for future use. Previous studies have indicated that BMSCs possess immune
      privileged properties, which avoid or actively suppress the immunological
      responses. Here we propose the hypothesis that the application of osteo-induced
      allogeneic BMSCs in fibrin gels for delivery of the cells by means of an
      injectable device would enhance repair of atrophic nonunion without the use of
      immunosuppressive therapy. Furthermore, fibrin gel could be useful as BMSCs
      carrier to deliver cells in vivo, there is no immunogenicity to be expected and
      BMSCs were able to spread and proliferate into the fibrin. Therefore, if the
      hypothesis is proved to be practical, it might represent a novel minimally
      invasive therapeutic approach and enhance atrophic nonunion repairing.

PMID- 21885205
TI  - Accomplishments of the thought disordered person: a case study in psychiatrist
      patient interaction.
AB  - BACKGROUND: The research and clinical literature portrays the thought disordered
      person as incapable of meaningful social interaction. This model views thought
      disorder exclusively as a brain dysfunction, evidenced by dysfunctions in speech.
      AIMS: The study seeks to address this deficit model by investigating the
      interactional accomplishments of thought disordered people in clinical
      interviews. METHOD: An analysis of clinical interview data. RESULTS: We
      investigate (1) what thought disordered people actually accomplish in
      interaction, and (2) how thought disordered people and their psychiatrists
      routinely communicate on matters consequential for treatment. CONCLUSIONS: This
      paper introduces a new perspective on the interactional achievements of people
      with thought disorder. The skills required by both parties during routine
      clinical interviews have not previously been recognised or described.

PMID- 21885206
TI  - Salting, drying and sensory quality of dry-cured hams subjected to different pre
      salting treatments: skin trimming and pressing.
AB  - The effects of skinning in a V-shape and pressing of hams on salting, drying and
      sensory characteristics of dry-cured hams were assessed. Salt and water contents
      and a(w) were determined in the central part of the ham during processing by
      computed tomography. Overall salt and water contents were also chemically
      analysed. Sensory analyses were performed on the final product. Partial skinning
      or pressing increased both salt uptake and final weight loss, but did not reduce
      the intra-batch variability in salt uptake. Moreover, trimmed hams exhibited a
      higher salt content in the inner areas of the hams after resting. Trimmed dry
      cured hams showed less metallic flavour, higher saltiness and more mature flavour
      in the biceps femoris muscle, and lower pastiness and adhesiveness as well as
      higher crumbliness and aged flavour in both the biceps femoris and the
      semimembranosus muscles. Pressing treatment caused less metallic flavour only in
      biceps femoris muscle and higher saltiness.

PMID- 21885207
TI  - Local-regional recurrence with and without radiation therapy after neoadjuvant
      chemotherapy and mastectomy for clinically staged T3N0 breast cancer.
AB  - PURPOSE: The purpose of this study was to determine local-regional recurrence
      (LRR) risk according to whether postmastectomy radiation therapy (PMRT) was used
      to treat breast cancer patients with clinical T3N0 disease who received
      neoadjuvant chemotherapy (NAC) and mastectomy. METHODS AND MATERIALS:
      Clinicopathology data from 162 patients with clinical T3N0 breast cancer who
      received NAC and underwent mastectomy were retrospectively reviewed. A total of
      119 patients received PMRT, and 43 patients did not. The median number of
      axillary lymph nodes (LNs) dissected was 15. Actuarial rates were calculated
      using the Kaplan-Meier method and compared using the log-rank test. RESULTS: At a
      median follow-up of 75 months, 15 of 162 patients developed LRR. For all
      patients, the 5-year LRR rate was 9% (95% confidence interval [CI], 4%-14%). The
      5-year LRR rate for those who received PMRT was 4% (95% CI, 1%-9%) vs. 24% (95%
      CI, 10%-39%) for those who did not receive PMRT (p <0.001). A significantly
      higher proportion of irradiated patients had pathology involved LNs and were <=40
      years old. Among patients who had pathology involved LNs, the LRR rate was lower
      in those who received PMRT (p <0.001). A similar trend was observed for those who
      did not have pathology involved LN disease. Among nonirradiated patients, the
      appearance of pathologic LN disease after NAC was the only clinicopathologic
      factor examined that significantly correlated with the risk of LRR. CONCLUSIONS:
      Breast cancer patients with clinical T3N0 disease treated with NAC and mastectomy
      but without PMRT had a significant risk of LRR, even when there was no pathologic
      evidence of LN involvement present after NAC. PMRT was effective in reducing the
      LRR rate. We suggest PMRT should be considered for patients with clinical T3N0
      disease.

PMID- 21885208
TI  - Ligament contribution to patterns of articular fractures of the distal radius.
AB  - PURPOSE: Intra-articular fractures of the distal radius are common injuries, but
      the correlation between ligament attachments and fracture location is poorly
      understood. The purpose of this study was to assess the location of intra
      articular fractures compared to the known ligament attachments of the distal
      radius. METHODS: The authors retrospectively reviewed computed tomography scans
      of acute intra-articular distal radius fractures performed at 1 institution
      between 2001 and 2008. Of 145 scans, 45 were deemed unsuitable due to poor
      quality or presence of internal fixation in the distal radius, leaving 100
      fractures for review. Fracture line locations of the distal radius were plotted
      to a standardized distal radius template and statistically analyzed for their
      relationship to known ligament attachments. RESULTS: Fracture lines were
      significantly more likely to occur at the intervals between the ligament
      attachments than at the ligament attachments. Common sites of fractures were the
      center of the sigmoid notch, between the short and long radiolunate ligaments,
      and the central and ulnar aspects of the scaphoid fossa dorsally. The sites of
      the ligament attachments to the distal radius were relatively protected. The
      likely site of the impaction of the carpus on the distal radius articular surface
      can often be construed from viewing the computed tomography scans, and the
      subsequent propagation of the fracture can be identified. CONCLUSIONS: Articular
      fractures of the distal radius are statistically more likely to occur between the
      ligament attachments. The ligamentous attachments of the distal radius to the
      volar carpus in an intra-articular distal radius fracture are relatively well
      preserved. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic III.

PMID- 21885209
TI  - [Physical violence during pregnancy in Morocco].
AB  - INTRODUCTION: Physical abuse are a serious social problem and an issue of
      perinatal health. MATERIAL AND METHODS: This article presents the results of a
      survey conducted at the CHU Ibn Rochd of Casablanca (Morocco), over a period of
      one year, in order to determine their frequency, risk factors, maternal diseases
      and obstetric complications. RESULTS: The results of our survey found that women
      who reported physical abuse have a frequency of 12.3% (107 cases). The average
      age of these women is 22.3 years; 65.6% of parturients are illiterate, 45% are
      from a disadvantaged socioeconomic status, 47% originated from a rural county;
      37% are unmarried; half of the abused are multiparous with an average of 3.2
      living children; 23% of the pregnancies are unplanned. Lastly, 37.3% of pregnant
      partners are unemployed and 67% have toxic habits. Obstetric complications are
      fairly frequent and mental effects are not negligible with 3 attempted suicides
      and attempted homicide. CONCLUSION: Early identification of abuse suffered by
      pregnant women and taking measures to prevent them could reduce the occurrence of
      these adverse effects.

PMID- 21885210
TI  - Major depression and treatment response in adolescents with ADHD and substance
      use disorder.
AB  - BACKGROUND: Major depressive disorder (MDD) frequently co-occurs in adolescents
      with substance use disorders (SUDs) and attention deficit hyperactivity disorder
      (ADHD), but the impact of MDD on substance treatment and ADHD outcomes and
      implications for clinical practice are unclear. METHODS: Adolescents (n=303; ages
      13-18) meeting DSM-IV criteria for ADHD and SUD were randomized to osmotic
      release methylphenidate (OROS-MPH) or placebo and 16 weeks of cognitive
      behavioral therapy (CBT). Adolescents with (n=38) and without (n=265) MDD were
      compared on baseline demographic and clinical characteristics as well as non
      nicotine substance use and ADHD treatment outcomes. RESULTS: Adolescents with MDD
      reported more non-nicotine substance use days at baseline and continued using
      more throughout treatment compared to those without MDD (p<0.0001 based on
      timeline followback; p<0.001 based on urine drug screens). There was no
      difference between adolescents with and without MDD in retention or CBT sessions
      attended. ADHD symptom severity (based on DSM-IV ADHD rating scale) followed a
      slightly different course of improvement although with no difference between
      groups in baseline or 16-week symptom severity or 16-week symptom reduction.
      There was no difference in days of substance use or ADHD symptom outcomes over
      time in adolescents with MDD or those without MDD treated with OROS-MPH or
      placebo. Depressed adolescents were more often female, older, and not court
      ordered. CONCLUSIONS: These preliminary findings suggest that compared to non
      depressed adolescents with ADHD and SUD, those with co-occurring MDD have more
      severe substance use at baseline and throughout treatment. Such youth may require
      interventions targeting depression.

PMID- 21885211
TI  - Assessing teen smoking patterns: the weekend phenomenon.
AB  - BACKGROUND: Adolescent cigarette smokers may have more daily variability in their
      smoking patterns than adults. A better understanding of teen smoking patterns can
      inform the development of more effective adolescent smoking cessation
      interventions. METHODS: Teen smokers seeking cessation treatment (N=366) reported
      the number of cigarettes smoked on each day of a typical week. A paired t-test
      was used to examine differences between weekday (Sunday-Thursday) and weekend
      (Friday-Saturday) smoking. Main effects and interactions for race/ethnicity and
      gender were assessed using a 2-way ANOVA for the following variables: typical
      weekly smoking, average weekday smoking, average weekend smoking, and difference
      between weekday and weekend smoking. Scheffe post hoc tests were used to analyze
      any statistically significant differences. RESULTS: There was significantly more
      weekend smoking compared to weekday smoking, p<0.001. The difference in weekday
      versus weekend smoking levels was larger for females than for males, p<0.05.
      Hispanics reported less typical weekly smoking, p<0.001, less weekday smoking,
      p<0.001, and less weekend day smoking, p<0.01, compared to Caucasians and multi
      racial teens. There was no difference in weekend day versus weekday smoking by
      race/ethnic background. CONCLUSIONS: Using a more detailed assessment of smoking
      quantity captures patterns of adolescent smoking that may lead to more effective
      smoking cessation interventions.

PMID- 21885212
TI  - Directly observed antiretroviral therapy eliminates adverse effects of active
      drug use on adherence.
AB  - BACKGROUND: The impact of adherence enhancing interventions on the relationship
      between active drug use and adherence is largely unknown. METHODS: We conducted a
      24-week randomized controlled trial of antiretroviral directly observed therapy
      (DOT) vs. treatment as usual (TAU) among HIV-infected methadone patients. Our
      outcome measure was pill count antiretroviral adherence, and our major
      independent variables were treatment arm (DOT vs. TAU) and active drug use
      (opiates, cocaine, or both opiates and cocaine). We defined any drug use as >= 1
      positive urine toxicology result, and frequent drug use as >= 50% tested urines
      positive. We used mixed-effects linear models to evaluate associations between
      adherence and drug use, and included a treatment arm-by-drug use interaction term
      to evaluate whether DOT moderates associations between drug use and adherence.
      RESULTS: 39 participants were randomized to DOT and 38 to TAU. We observed
      significant associations between adherence and active drug use, but these were
      limited to TAU participants. Adherence was worse in TAU participants with any
      opiate use than in TAU participants without (63% vs. 75%, p<0.01); and worse
      among those with any polysubstance (both opiate and cocaine) use than without
      (60% vs. 73%, p=0.01). We also observed significant decreases in adherence among
      TAU participants with frequent opiate or frequent polysubstance use, compared to
      no drug use. Among DOT participants, active drug use was not associated with
      worse adherence. CONCLUSIONS: Active opiate or polysubstance use decreases
      antiretroviral adherence, but the negative impact of drug use on adherence is
      eliminated by antiretroviral DOT.

PMID- 21885213
TI  - Respondent-driven sampling to recruit young adult non-medical users of
      pharmaceutical opioids: problems and solutions.
AB  - Respondent-driven sampling (RDS) has been promoted as a superior method in
      recruiting hard-to-reach and hidden populations. Although its application has
      expanded enormously, there remains a need for empirical data evaluating the
      performance of RDS in different settings. This study describes the application of
      RDS to recruit a community sample (N=396) of young adults (18-23 years old) into
      a natural history study of non-medical pharmaceutical opioid use. Since
      recruitment targeted non-dependent pharmaceutical opioid users, and applied other
      eligibility restrictions, several modifications had to be made to make RDS work
      with this narrowly defined target population. RDS recruitment was less efficient
      than expected, and produced greater numbers of African American recruits than
      anticipated. Although the sampling quota was met, sample analysis revealed a lack
      of equilibrium in terms of ethnic composition and very strong in-group
      recruitment tendencies among White and African American respondents. This study
      contributes potentially helpful insights into the strengths and limitations of
      using RDS which may benefit future studies.

PMID- 21885214
TI  - The neurobiology of cognitive control in successful cocaine abstinence.
AB  - INTRODUCTION: Extensive evidence demonstrates that current cocaine abusers show
      hypoactivity in anterior cingulate and dorsolateral prefrontal cortex and respond
      poorly relative to drug-naive controls on tests of executive function. Relatively
      little is known about the cognitive sequelae of long-term abstinence in cocaine
      addicts. METHODS: Here, we use a GO-NOGO task in which successful performance
      necessitated withholding a prepotent response to assay cognitive control in short
      and long-term abstinent cocaine users (1-5 weeks and 40-102 weeks,
      respectively). RESULTS: We report significantly greater activity in prefrontal,
      cingulate, cerebellar and inferior frontal gyrii in abstinent cocaine users for
      both successful response inhibitions and errors of commission. Moreover, this
      relative hyperactivity was present in both abstinent groups, which, in the
      presence of comparable behavioral performance, suggests a functional
      compensation. CONCLUSIONS: Differences between the short- and long-abstinence
      groups in the patterns of functional recruitment suggest different cognitive
      control demands at different stages in abstinence. Short-term abstinence showed
      increased inhibition-related dorsolateral and inferior frontal activity
      indicative of the need for increased inhibitory control while long-term
      abstinence showed increased error-related ACC activity indicative of heightened
      behavioral monitoring. The results suggest that the integrity of prefrontal
      systems that underlie cognitive control functions may be an important
      characteristic of successful long-term abstinence.

PMID- 21885216
TI  - Isolation and characterization of influenza A virus (subtype H5N1) that caused
      the first highly pathogenic avian influenza outbreak in chicken in Bhutan.
AB  - We characterized Influenza A/H5N1 virus that caused the first outbreak of highly
      pathogenic avian influenza (HPAI) in chickens in Bhutan in 2010. The virus was
      highly virulent to chicken, killing them within two days of the experimental
      inoculation with an intravenous pathogenicity index (IVPI) of 2.88. For genetic
      and phylogenetic analyses, complete genome sequencing of 4 viral isolates was
      carried out. The isolates revealed multiple basic amino acids at their
      hemagglutinin (HA) cleavage site, similar to other "Qinghai-like" H5N1 isolates.
      The receptor-binding site of HA molecule contained avian-like amino acids ((222)Q
      and (224)G). The isolates also contained amino acid residue K at position 627 of
      the PB2 protein, and other markers in NS 1 and PB1 proteins, highlighting the
      risk to mammals. However, the isolates were sensitive to influenza drugs
      presently available in the market. The sequence analysis indicated that the
      Bhutan viruses shared 99.1-100% nucleotide homology in all the eight genes among
      themselves and 2010 chicken isolate from Bangladesh (A/chicken/Bangladesh/1151
      11/2010) indicating common progenitor virus. The phylogenetic analysis indicated
      that the Bhutan isolates belonged to sub-clade 2.2.3 (EMA 3) and shared common
      progenitor virus with the 2010 Bangladesh virus. Based on the evidence of
      phylogeny and molecular markers, it could be concluded that the outbreaks in
      Bhutan and Bangladesh in 2010 were due to independent introductions of the virus
      probably through migratory birds.

PMID- 21885215
TI  - Access to a running wheel decreases cocaine-primed and cue-induced reinstatement
      in male and female rats.
AB  - BACKGROUND: Relapse to drug use after a period of abstinence is a persistent
      problem in the treatment of cocaine dependence. Physical activity decreases
      cocaine self-administration in laboratory animals and is associated with a
      positive prognosis in human substance-abusing populations. The purpose of this
      study was to examine the effects of long-term access to a running wheel on drug
      primed and cue-induced reinstatement of cocaine-seeking behavior in male and
      female rats. methods: Long-Evans rats were obtained at weaning and assigned to
      sedentary (no wheel) and exercising (access to wheel) groups for the duration of
      the study. After 6 weeks, rats were implanted with intravenous catheters and
      trained to self-administer cocaine for 14 days. After training, saline was
      substituted for cocaine and responding was allowed to extinguish, after which
      cocaine-primed reinstatement was examined in both groups. Following this test,
      cocaine self-administration was re-established in both groups for a 5-day period.
      Next, a second period of abstinence occurred in which both cocaine and the
      cocaine-associated cues were withheld. After 5 days of abstinence, cue-induced
      reinstatement was examined in both groups. RESULTS: Sedentary and exercising rats
      exhibited similar levels of cocaine self-administration, but exercising rats
      responded less than sedentary rats during extinction. In tests of cocaine-primed
      and cue-induced reinstatement, exercising rats responded less than sedentary
      rats, and this effect was apparent in both males and females. CONCLUSIONS: These
      data indicate that long-term access to a running wheel decreases drug-primed and
      cue-induced reinstatement, and that physical activity may be effective at
      preventing relapse in substance-abusing populations.

PMID- 21885217
TI  - Pathogenicity and immunogenicity of three Mycoplasma gallisepticum isolates in
      house finches (Carpodacus mexicanus).
AB  - Mycoplasma gallisepticum (MG) has become a common cause of conjunctivitis in free
      living house finches (Carpodacus mexicanus) since its emergence in the early
      1990s. To date, temporal and spatial genotypic variation in MG has been
      documented, but phenotypic variation in pathogenicity and immunogenicity has not
      been examined. House finches were inoculated with MG isolates Virginia (VA)1994,
      California (CA)2006, or North Carolina (NC)2006, which were cultured from free
      living house finches with conjunctivitis in 1994, 2006, and 2006, respectively.
      Infection with NC2006 resulted in the most severe eye lesions, highest pathogen
      loads, and highest levels of pathogen-specific lachrymal and serum antibodies.
      Infection with CA2006 caused the least severe eye lesions, lowest pathogen load,
      and lowest levels of antibodies. A small number of birds in each group developed
      protracted, severe disease in spite of robust antibody responses, suggesting that
      immunopathology may contribute to the lesions. Immunoblot analyses indicated that
      isolates are antigenically similar; thus, there may be partial cross-protection
      if a house finch encounters two or more strains of MG throughout the course of
      its lifetime. This study provides evidence that MG strains or strain variants
      circulating in house finch populations vary in their ability to cause disease,
      induce antibody responses, and persist in the host.

PMID- 21885218
TI  - Use of ovotransferrin as an antimicrobial in turkeys naturally infected with
      Chlamydia psittaci, avian metapneumovirus and Ornithobacterium rhinotracheale.
AB  - Respiratory pathogens are difficult to control in large-scale turkey production.
      This report describes a clinical trial of antimicrobial ovoTF aerosol on a large
      Belgian turkey farm. ovoTF was administered to reduce Chlamydia psittaci (C.
      psittaci) infections and to study the impact of this action on the occurrence of
      Ornithobacterium rhinotracheale (O. rhinotracheale) and avian metapneumovirus
      (aMPV) infections. Two subsequent broods were included; (i) a control brood
      receiving no ovoTF and (ii) an ovoTF brood receiving ovoTF aerosol (5mg/animal)
      at the age of 2 weeks, continuing daily for 12 days. Twenty-four one-day-old toms
      of the control and ovoTF brood were tagged and monitored for 15 weeks. The
      control brood experienced two periods of respiratory disease, the first (2-3
      weeks of age) due to C. psittaci and the second (8-17 weeks of age) in the
      presence of C. psittaci, O. rhinotracheale and maybe aMPV. Extensive antibiotic
      treatment was needed in 2, 8 and 9 week-old toms. In the ovoTF brood, toms stayed
      healthy until the age of 9 weeks, whereafter respiratory disease occurred in the
      presence of C. psittaci, O rhinotracheale and aMPV. OvoTF administration: (i)
      reduced the amount of C. psittaci in the air as demonstrated by bioaerosol
      monitoring, (ii) prevented respiratory disease during the first half of the brood
      period, (iii) was associated with 46% reduction of mortality, and (iv) reduced
      the antibiotic cost. Our results justify additional clinical trials to explore
      the use of this innovative antimicrobial strategy for poultry.

PMID- 21885219
TI  - Measurement and analysis of diastereomer ratios for forensic characterization of
      brodifacoum.
AB  - The highly toxic anticoagulant rodenticide brodifacoum is an organic compound
      that has two diastereomeric forms. In this paper, we consider the hypothesis that
      the relative population of the diastereomers is a characteristic of forensic
      value for the association or source attribution of specimens of brodifacoum. In
      general, the stereoisomer distribution in an organic compound depends on the
      reagents, conditions, and methods used for synthesis and purification, and may
      vary over time due to differential stabilities of the stereoisomers. The
      stereoisomer distribution may thus serve as an identifier of the production
      methods and history of samples and provide a basis for comparing recovered
      specimens. We refer to this novel approach for signature detection as
      stereoisomer distribution analysis or SDA. If the stereoisomers are
      diastereomers, quantitative determination of the diastereomer ratio in a specimen
      can be performed by a number of techniques, notably gas or liquid chromatography
      or nuclear magnetic resonance (NMR) spectroscopy. This paper describes an NMR
      spectroscopic analysis of ten commercial technical grade brodifacoum samples from
      distinct batches originating from three different sources. The results reveal
      detectable source-to-source and batch-to-batch variations in diastereomer ratios.

PMID- 21885220
TI  - Quantitative assessment of evidential weight for a fingerprint comparison. Part
      II: a generalisation to take account of the general pattern.
AB  - The authors have proposed a quantitative method for assessing weight of evidence
      in the case where a fingermark from a crime scene is compared with a set of
      control prints from the ten fingers of a suspect. The approach is based on the
      notion of calculating a Likelihood Ratio (LR) that addresses a pair of
      propositions relating to the individual who left the crime mark. The current
      method considers only information extracted from minutiae, such as location,
      direction and type. It does not consider other information usually taken into
      account by fingerprint examiners, such as the general pattern of the ridge flow
      on the mark and the control prints. In this paper, we propose an improvement to
      our model that allows a fingerprint examiner to take advantage of pattern
      information when assessing the evidential weight to be assigned to a fingerprint
      comparison. We present an extension of the formal analysis proposed earlier and
      we illustrate our approach with an example.

PMID- 21885221
TI  - The efficiency of Nose Obstruction Symptom Evaluation (NOSE) scale on patients
      with nasal septal deviation.
AB  - OBJECTIVE: The aim in this study was to evaluate the efficiency of Nasal
      Obstruction Symptom Evaluation (NOSE) scale for septoplasty (without turbinate
      reduction) in comparison with other examination methods. METHODS: Prospective
      observational study was undertaken in otolaryngology department of university
      hospital. NOSE scale for quality of life assessment, visual analog scale for
      examination findings, acoustic rhinometry and coronal computed tomography were
      performed before and after septoplasty. The efficiency of NOSE scale to assess
      for septoplasty results and the correlation between NOSE scores and other
      techniques was analyzed. RESULTS: Twenty-seven patients underwent septoplasty;
      there was a very significant improvement in mean NOSE scores of patients (60.2
      versus 11.28, p<0.01). There was no correlation between NOSE scores and acoustic
      rhinometry. Correlation was found between NOSE scores and examination and
      computed tomography findings (p<0.05). CONCLUSION: NOSE scale that is well
      correlated with examination findings and computed tomography, is very useful tool
      to evaluate the effectiveness of pure septoplasty.

PMID- 21885223
TI  - Ultrastructual morphology of juvenile psammomatoid ossifying fibroma.
AB  - We investigated the ultrastructural morphology of the hard tissue in a fibro
      osseous lesion. Bone samples were obtained from a juvenile psammomatoid ossifying
      fibroma and were observed under a scanning electron microscope. The lesion had a
      spongy lamellar structure containing bony tissue. On histological examination,
      resorbing preexisting lamellar bone associated with a large number of cathepsin K
      positive osteoclasts was confirmed. Scanning electron microscopy revealed the
      bony material to have a cribriform structure and to indicate resorption related
      to osteoclasts throughout the tumor. These characteristic findings revealed the
      presence of active bony reconstruction and destruction in this lesion. The spongy
      calcified structure observed by scanning electron microscopy expressed the
      characteristic ground glass appearance in computed tomography of this patient.
      This remarkable activation of osteoclasts may deeply relate to characteristic
      calcified structure in this lesion. Observation of hard tissue structure under a
      scanning electron microscope may shed light on the pathology of fibro-osseous
      lesions in the head and neck.

PMID- 21885222
TI  - Clinical impact of iodine staining for diagnosis of carcinoma in situ in the
      floor of mouth, and decision of adequate surgical margin.
AB  - OBJECTIVE: The use of iodine staining has been recommended for the early
      detection of squamous cell carcinoma (SCC) in the upper aerodigestive tract. The
      purpose was to verify the effectiveness of iodine staining in detecting early
      squamous cell carcinoma in the floor of mouth. METHODS: Between 1995 and 2005,
      otolaryngological examinations including the floor of mouth were performed for
      2278 esophageal cancer patients as a screening program of high-risk patient
      group. Iodine staining was applied to a lightly reddish and/or white patch,
      and/or uneven lesions in the floor of the mouth. Forceps biopsy was performed for
      demarcated unstained or lightly stained lesions. Three patients with the tumors
      in the floor of mouth, which were diagnosed as more over T2 level just by visual
      examination, were excluded from this study. If SCC was found in the specimen,
      mucosal resection was performed with a safety margin of 2mm from the unstained or
      lightly stained lesion. The incidence, rate of carcinoma in situ, and prognosis
      of cancer of the floor of mouth (CFOM) were assessed. RESULTS: Iodine staining
      was performed for 72 of 2278 patients (3.2%) according to the presence of
      suspicious reddish and/or whitish and/or uneven lesions. Of these, unstained or
      lightly stained areas after iodine staining were recognized in 47 patients and
      SCC was revealed in 28 of 47 patients. The diagnosis of other 19 patients
      included inflammatory mucosa (n=11), low grade dysplasia (n=6), and
      hyperkeratosis (n=2). Sensitivity and specificity of iodine staining for
      detecting SCC were 100% and 59.6%, respectively. Pathological diagnosis of the 28
      patients included squamous cell carcinoma in situ (n=12), microinvasive squamous
      cell carcinoma (n=15) disease, and focal invasive squamous cell cancer (n=1).
      Twenty-four of 28 patients were treated with mucosal resection without mandible
      resection. The other 4 patients did not receive the treatment of CFOM due to
      concomitant far advanced esophageal cancer. In 24 patients undergoing mucosal
      resection, no patients developed local recurrence or metastasis to the cervical
      lymph nodes during an average of 74.2 months of follow-up period (from 7 to 156
      months). The 5-year cause-specific survival of these patients was 100%.
      CONCLUSION: The use of iodine staining as a part of otolaryngological
      examinations may be beneficial for the early detection of CFOM, including
      carcinoma in situ and micro-invasive SCC. Moreover, it would be very useful to
      determine an adequate surgical margin for locally mucosal resection.

PMID- 21885224
TI  - Epstein-Barr virus-associated smooth muscle tumor of the tonsil.
AB  - Smooth muscle tumors of the tonsil are rare. Recently, the occurrence of Epstein
      Barr virus-associated smooth muscle tumor (EBV-SMT) has been increasingly
      recognized in immunocompromised patients, mainly post-transplantation and AIDS
      patients. The clinicopathologic features of EBV-SMT are different from
      conventional smooth muscle tumors. To the best of our knowledge, EBV-SMT
      involving the tonsil in an AIDS patient has not been reported. A 27-year-old man
      presented with a 2.2cm right tonsillar mass six months after AIDS diagnosis. The
      tumor was composed of a cellular proliferation of oval to spindle-shaped cells
      with mitotic count up to 10 in 10 high-power fields. The diagnosis of EBV-SMT was
      confirmed by in situ hybridization for EBV-encoded RNA (EBER) transcripts.
      Synchronous lesions were also detected in the liver and peritoneum by an
      abdominal computed tomographic scan. EBV-SMT should be included in the
      differential diagnoses of a mesenchymal tumor in immunocompromised patients, and
      in the differential diagnoses of a smooth muscle tumor occurring in uncommon
      sites including the tonsil.

PMID- 21885225
TI  - Surgical management of large juvenile nasopharyngeal angiofibroma invading the
      infratemporal fossa with intracranial extradural parasellar involvement in an 8
      year-old boy.
AB  - We present a rare case of a large juvenile nasopharyngeal angiofibroma (JNA) in
      an 8-year-old boy. Preoperative imaging revealed that the tumor had widely
      extended to the sphenoid sinus, infratemporal fossa, and cavernous sinus.
      Following embolization of the feeding vessels, the tumor was successfully removed
      by a combination of an orbitozygomatic approach and Le Fort I osteotomy under
      frontolateral craniotomy. An endoscope assisted in the surgery. At 15 months
      follow-up, the patient was free of the disease with no facial palsy, scars, or
      malocclusion. JNA is a benign tumor that typically affects adolescent males and
      is rarely observed during prepuberty. Complete removal of JNA by surgery, the
      initial therapy, is generally required. However, as in the present case, a large
      JNA with wide extension requires extended surgery, and such a surgery is more
      invasive for prepubertal patients. Using an appropriate combination of surgical
      approaches, a large JNA developed during prepuberty can be safely removed with
      reduced morbidity.

PMID- 21885226
TI  - External jugular vein aneurysm: a rare cause of neck swelling. A report of three
      patients.
AB  - Venous aneurysms are a relatively rare pathology, far less common than arterial
      aneurysms. Unrelated to either age or gender, they can affect any vein, including
      cervical, thoracic, visceral, and lower limb veins. Aneurysmal dilatations in
      cervical veins are rare due to low pressure in the vena cava system; they can
      involve any vein but most frequently are observed on the internal and external
      jugular veins. This report of three patients highlights some of the specific
      diagnostic and therapeutic features of this pathology.

PMID- 21885228
TI  - Characterization of seventy polymethoxylated flavonoids (PMFs) in the leaves of
      Murraya paniculata by on-line high-performance liquid chromatography coupled to
      photodiode array detection and electrospray tandem mass spectrometry.
AB  - A sensitive HPLC-DAD-ESI-MS/MS method was established to screen and identify the
      polymethoxylated flavonoids (PMFs) in the leaves of Murraya paniculata (L.) Jack.
      16 PMF standards were first to be analyzed in positive mode by the CID-MS/MS. For
      polymethoxylated flavones, the fragments of [M+H-n*15](+) produced by loss of one
      or more methyl radicals from the protonated molecule, as well as [M+H-16](+),
      [M+H-28](+), [M+H-29](+), [M+H-31](+), [M+H-33](+), [M+H-43](+), [M+H-44](+),
      [M+H-46](+) and [M+H-61](+) fragment ions were detected, which could be taken as
      their diagnostic characters. For polymethoxylated flavanones and chalcones, their
      [M+H](+) ions usually underwent RDA cleavage fragmentation of the C-ring prior to
      the similar loss of diagnostic fragment ions as polymethoxylated flavones, which
      could be adopted as a shortcut to distinguish them from ordinary flavones
      rapidly. For the PMF glycosides, the neutral loss of the similar fragments with
      polymethoxylated flavones from their [aglycone+H](+) could be adopted as a simple
      method to screen them out from complex mixture. Based on these characterizations
      of PMFs and the results of EIC-MS/MS experiment, 70 PMFs including 45 flavones,
      17 flavanones or chalcones and 8 PMFs glycosides were screened out from the
      complex extract of the leaves of M. paniculata. Among them, 16 compounds were
      unambiguously identified by comparison with reference substances. The results
      indicated that the developed analysis method could be employed as a rapid,
      effective technique for structural characterization of PMFs.

PMID- 21885227
TI  - The genus Allochromatium (Chromatiales Chromatiaceae) revisited: a study on its
      intragenic structure based on multilocus sequence analysis (MLSA) and DNA-DNA
      hybridization (DDH).
AB  - In this study, the taxonomic status of anoxygenic photosynthetic bacteria
      belonging to the genus Allochromatium is revisited. The inter- and intraspecies
      relationship of seven Allochromatium strains, including a set of well described
      type strains, were examined by DNA-DNA hybridization (DDH) and multilocus
      sequence analysis (MLSA) using segments of seven protein-coding genes. The re
      sequencing of the 16S rRNA, the internal transcriber spacer (ITS), multi-gene
      analysis and DDH comparison indicated that both type strains Allochromatium
      vinosum DSM 180(T) and Allochromatium minutissimum DSM 1376(T) are closely
      related to each other forming an independent cluster together with the strains A.
      vinosum DSM 183 and DSM 1686. The internal comparison of members of this A.
      vinosum phylogroup showed values of DDH relatedness above 80% and concatenated
      sequence similarities (4744bp) above 98%. In contrast, the MLSA scheme has
      identified A. vinosum strain BH-2 as a separate lineage. Strain BH-2 was first
      classified as a member of the species A. vinosum based on DDH comparison.
      However, this strain showed the lowest similarity values of the 16S rRNA gene and
      concatenated sequences, as well as amino acid identity (AAI) when compared to
      other Allochromatium strains, suggesting that strain BH-2 may represent a new
      species.

PMID- 21885229
TI  - Development of a LC-ESI-MS3 method for determination of nitrendipine in human
      plasma.
AB  - A novel and sensitive method utilizing high performance liquid chromatography
      coupled with electrospray ionization source tandem mass spectrometry (LC-ESI
      MS(3)) was developed for the first time in order to analyze nitrendipine in human
      plasma samples. Human plasma samples were prepared by protein precipitation with
      acetonitrile and well resolved on a 100 mm reversed-phase column in gradient
      elution with 0.05% (v/v) formic acid in acetonitrile as the mobile phase.
      Determination was performed in MS(3) scan mode for nitrendipine and in the
      multiple reaction monitoring (MRM) mode for nimodipine (internal standard). This
      method, having a lower limit of quantification (LLOQ) of 0.05 ng/mL when using a
      100 MUL sample aliquot (5 pg/sample), is acceptable for calibration of the
      linearity and repeatability and is of better sensitivity than the reported
      methods (>0.25 ng/mL). The major advantages of the method are that small sample
      volume (100 MUL) is required, simple sample processing technique, high
      sensitivity and excellent selectivity is guaranteed by the MS(3) detection. The
      proposed validated method has been successfully applied to a clinical study on
      nitrendipine.

PMID- 21885230
TI  - Clinical utility of QuantiFERON-TB GOLD In-Tube and tuberculin skin test in
      patients with tuberculous pleural effusions.
AB  - Interferon gamma release assays are used for diagnosing latent tuberculosis (TB);
      however, their role in diagnosing tuberculous pleural effusion (TPE) is not
      defined. The aim of this study was to evaluate the usefulness of the QuantiFERON
      TB Gold In-Tube assay (QFT-IT) and compare this assay with the tuberculin skin
      test (TST) for diagnosing TPE in settings where tuberculosis is endemic and
      bacillus Calmette-Guerin vaccination is mandatory. The TST and QFT-IT test were
      conducted prospectively with 101 patients presenting with clinically suspected
      TPE. Of the 97 evaluable subjects, 54 had TPE. The sensitivity, specificity,
      positive predictive value, and negative predictive value were, respectively,
      76.9%, 61.1%, 74.1%, and 64.7% for QFT-IT; 72.5%, 71.7%, 77.1%, and 66.7% for
      TST; and 83.7%, 45.7%, 68.3%, and 66.7% for QFT-IT plus TST. Thus, the QFT-IT
      test may be more useful than the TST for diagnosing TPE. Although the combination
      of QFT-IT and TST had higher sensitivity, it had poor specificity owing to the
      high prevalence of latent TB in our setting.

PMID- 21885231
TI  - Characterization of serum-free buffalo granulosa cell culture and analysis of
      genes involved in terminal differentiation from FSH- to LH-responsive phenotype.
AB  - In the present study, buffalo granulosa cells were cultured under serum-free
      conditions and characterized to study the changes in gene expression associated
      with the transition of granulosa cells from estrogen- to progesterone-secreting
      phenotype. The cells were cultured in vitro under completely serum-free
      conditions for 8 d. Gene expression and hormone analysis showed that on day 4
      granulosa cells exhibit FSH responsiveness with preovulatory phenotype having
      highest CYP19 gene expression and 17beta-estradiol production, whereas a
      significant increase in transcript abundance of STAR, CYP11, and HSD3B genes
      accompanied with an increase in progesterone production was observed on day 8.
      Cells treated with LH on day 4 followed by gene expression analysis at 1, 2, 4,
      6, 18, and 24 h showed significant increase in transcripts of LH-responsive
      genes. In conclusion, culture condition used in the present study showed that
      granulosa cells were FSH responsive and attained attributes of granulosa cells of
      dominant follicles at day 4 with highest CYP19 and LHR gene expression beyond
      which they acquired the ability to luteinize and thus were more LH responsive. In
      addition, after LH treatment, analysis of early LH-responsive genes (EGR2, RUNX1,
      and NR4A1) on day 4 showed that granulosa cells at this stage in culture exhibits
      phenotype similar to that of preovulatory follicles before LH surge in vivo and
      corresponds to the in vivo transition of well-orchestrated gene expression
      profile after LH surge. The characterized culture conditions represent a suitable
      in vitro model for analysis of genes involved in terminal differentiation of
      granulosa cells from FSH- to LH-responsive phenotype during folliculogenesis in
      buffalo.

PMID- 21885232
TI  - [Adverse drug reactions of strontium ranelate(Protelos((r)) in France].
AB  - OBJECTIVE: Study of side effects (SE) associated with strontium ranelate required
      by the French Drug agency (Afssaps). METHOD: SE associated with strontium
      ranelate and spontaneously reported until March 2009 to the manufacturer or to
      the French Regional Pharmacovigilance Centers and the periodic safety reports
      have been analyzed. Utilisation and sales data have been obtained from the
      manufacturer. RESULTS: During the 3 years of the study, 844 SE have been reported
      in France in patients treated with strontium ranelate. The 199 severe SE are
      cardiovascular (52%), cutaneous (26%), hepatodigestive (6%), neurological (5%),
      haematological (3%), osteomuscular (3%) and various (3%). Venous thromboembolic
      events (VTEE) are the most frequent cardiovascular SE (93/104) with an incidence
      of 1/31,052 months of treatment. At least one VTEE risk factor is present in 26
      (28%) patients. DRESS syndrome which median delay of advent is 35 days is the
      most frequent cutaneous SE (19/51 SE) with an incidence of 1/13,725 months of
      treatment. The 14 severe hepatodigestive SE are hepatitis (n=5), pancreatitis
      (n=2) and various others SE (n=7). The 10 severe neurological SE are
      confusion/amnesia (n=5), convulsions (n=4) and parenthesis (n=1). The seven
      severe haematological SE are pancytopenia (n=5), erythroblastopenia (n=1) and
      thrombocytopenic purpura (n=1). Among the seven deaths, only three (two pulmonary
      embolisms, one DRESS syndrome) are attributable to strontium ranelate. Apart from
      the severe SE, 685 SE have also been reported because strontium ranelate was the
      only drug with an imputability "suspect". DISCUSSION: Anti-fractural effect of
      strontium ranelate is at least as equal as those of bisphosphonates. Its usual SE
      are benign but two severe risks of strontium ranelate i.e. VTEE and DRESS
      syndrome are confirmed. The profile of tolerability, different from the one of
      bisphosphonates makes strontium ranelate as an alternative when bisphosphonates
      are not recommended or contraindicated (renal insufficiency for example).
      CONCLUSION: If DRESS syndrome is unpredictable, the one of VTEE could be reduced
      by a strontium ranelate contraindication for patients with a history of VTEE and
      by stopping the drug if a new VTEE risk situation happens.

PMID- 21885233
TI  - [Necrobiotic xanthogranuloma revealing an IgA gammapathy].

PMID- 21885234
TI  - Organising pneumonia and mesenteric plasmocytoma: a fortuitous association?

PMID- 21885235
TI  - [Strontium ranelate(Protelos(r)): who really benefits of the doubt?].

PMID- 21885236
TI  - [Premature delivery of an African woman in a febrile context].

PMID- 21885237
TI  - [Measles and pregnancy].
AB  - Because of insufficient vaccine coverage, there is an outbreak of measles since
      2008 in France with an increasing incidence of cases, most of them among children
      less than 1 year old or young adults. When measles occurs during pregnancy,
      maternal and fetal morbidity is increased. Particularly pregnant women are
      exposed to a higher risk of severe respiratory distress that might cause death.
      Measles virus can be detected in the placenta. Placental infection appears to be
      involved in some cases of fetal death. The virus is not responsible for
      congenital defects but can induce histologic damages inside the placenta which
      may lead to fetal death. Major perinatal risks are also miscarriage and
      prematurity. When measles occurs in late pregnancy, congenital infection is
      possible with variable expression and a risk of subacute sclerosing
      panencephalitis. Non immune pregnant women or neonates exposed to measles should
      receive an immunoglobulin prophylaxis within 6 days after contact in order to
      reduce the risk of infection and severe morbidity. In case of declared measles
      infection, symptomatic treatment can be proposed and tocolysis can be used if
      preterm labor is associated. Daily fetal monitoring during the 14 days following
      the beginning of the eruption can be offered when the fetus is viable.
      Vaccination is recommended for the people born in France after 1980 with 2 doses
      of vaccine against measles, rubeola and mumps. Measles vaccine, an attenuated
      living vaccine, should not be administered during pregnancy but must be proposed
      before pregnancy or during the post-partum period.

PMID- 21885238
TI  - [Chronic renal failure: what has changed in the last two decades].

PMID- 21885239
TI  - [How to manage mineral metabolism disorders in renal failure].
AB  - Mineral metabolism abnormalities are frequently observed in patients with chronic
      kidney disease (CKD). The bone and cardiovascular consequences should lead to the
      implementation of some adapted strategies for the prevention and treatment on the
      basis of the physiopathology of the disease and international recommendations.
      Biological bone markers such as serum parathyroid hormone (PTH) and alkaline
      phosphatase (ALP) are necessary to classify bone diseases without the need for
      bone biopsy. Elevated levels of bone markers are detected in cases of secondary
      hyperparathyroidism (SHPT), whereas decreased levels are observed in cases of
      adynamic bone disease (ABD). Bone mineral density, however, is not useful for the
      diagnosis. Vitamin D supplementation and reducing hyperphosphataemia by dietary
      phosphate-intake restriction, phosphate binders, and dialysis, are the main steps
      for the prevention of SHPT. Calcitriol analogs and calcimimetics should be used
      in second line in cases of SHPT. For the treatment of ABD, excess use of calcium
      salts and calcitriol analogs need to be avoided. Managing these therapies
      adequately can help maintain the main biological values (i.e. serum PTH, calcium,
      phosphorus, and ALP) within their recommended ranges.

PMID- 21885240
TI  - Comorbidities and mortality associated with hospitalized heart failure in Canada.
AB  - BACKGROUND: Heart failure (HF) is a leading morbid cause of hospitalization and
      death. HF is often accompanied by comorbid conditions, increasing the health care
      burden. This study describes hospital mortality and identifies comorbid
      conditions associated with HF. METHODS: Acute care hospital separations in 2005
      2006, with a diagnosis of HF I50, I500, I501, I509 (The International Statistical
      Classification of Diseases and Related Health Problems, Tenth Revision, Canada
      [ICD-10-CA]) were identified from all Canadian jurisdictions except Quebec.
      RESULTS: A total of 2,457,527 hospital separations among 1,812,923 individuals,
      identifying 8,212,869 diagnoses were reported. Among those, a total of 33,693
      (1.9%) of all hospitalized individuals had a most responsible diagnosis of HF,
      accounting for 42,399 hospital separations. Further, HF was coded 77,049 times as
      a comorbid diagnosis, altogether occurring in 4.9% of all hospitalizations. The
      most common primary diagnoses associated with comorbid HF were acute myocardial
      infarction (AMI), chronic obstructive pulmonary disease (COPD), and pneumonia.
      Seniors had a much higher hospitalization rate due to HF. Hospitalized
      individuals with a primary diagnosis of HF had an almost 3-fold higher 30-day in
      hospital mortality rate and nearly double the mean hospital stay than that for
      all causes. On average, hospitalizations with a primary diagnosis of HF had 3.9
      comorbidities, most commonly chronic ischemic heart disease (IHD), atrial
      fibrillation and flutter, diabetes, renal failure, etc.; 1.7 times greater for HF
      than for all causes. CONCLUSIONS: HF has a high in-hospital mortality rate
      particularly among the elderly and is associated with many cardiac and noncardiac
      conditions. HF necessitates long hospital stays, which increases the burden on
      the health care system in Canada.

PMID- 21885241
TI  - Delayed immune-mediated thrombocytopenia after re-exposure to abciximab therapy.
AB  - Abciximab is a potent antiplatelet agent that is increasingly being used to
      prevent ischemic complications of percutaneous coronary revascularization.
      Thrombocytopenia, including acute profound thrombocytopenia, has been reported to
      occur with this agent, but usually within 1 to 2 days of exposure. We report the
      case of a woman aged 68 years who presented with profound delayed
      thrombocytopenia 9 days after a second exposure to abciximab. She was treated
      successfully with intravenous immunoglobulin with complete resolution of the
      thrombocytopenia and no subsequent recurrences.

PMID- 21885242
TI  - Palliative care for heart failure: more than is written.

PMID- 21885243
TI  - A modified cement spacer technique for infected total hip arthroplasties with
      significant bone loss.
AB  - Complications related to femoral spacers are common during addressing infected
      total hip arthroplasties by 2-stage revision. We evaluated 11 patients who had 2
      stage revisions with massive bone loss after removal of the infected components
      by a trochanteric osteotomy. All femoral cement spacers were assembled on
      intramedullary nails. Femurs were protected by a plate, whereas acetabuli were
      augmented by a cage or roof ring depending on the remaining bone stock. This
      additional hardware was covered with antibiotic-impregnated cement. Infection was
      eradicated in 10 (90.9%) of 11 patients within 3.5 months in average. None of the
      patients had spacer fracture, periprosthetic fracture, or dislocation.
      Augmentation by hardware covered with antibiotic-impregnated cement is effective
      and may reduce complications until definitive treatment is performed.

PMID- 21885244
TI  - Massive and submassive pulmonary embolism: experience with an algorithm for
      catheter-directed mechanical thrombectomy.
AB  - BACKGROUND: The role of catheter-directed mechanical thrombectomy (CDMT) for the
      treatment of massive pulmonary embolism (MPE) and submassive pulmonary embolism
      (SMPE) is not clearly defined. We report our experience with an algorithm for
      CDMT as a primary treatment in patients with MPE and SMPE. METHODS: We
      retrospectively reviewed our experience in treating MPE and SMPE in consecutive
      patients over a 2-year period (2008-2010). Patients with computed tomography
      angiography evidence of saddle, main branch, or >=2 lobar pulmonary emboli in the
      setting of hypoxia, tachycardia, echocardiographic right heart strain, and/or
      cardiogenic shock underwent AngioJet CDMT, with or without adjunctive
      thrombolytic power-pulse spray. Outcomes, including angiographic success,
      clinical improvement, complications, and survival to discharge, were evaluated.
      RESULTS: Fifteen patients (8 men, 7 women; 14 SMPE, 1 SMPE) with a mean age of 59
      years (range: 35-90 years) were treated for heart strain (100%), tachycardia
      (67%), hypoxia (67%), and cardiogenic shock (7%). Ten patients (67%) also
      received Alteplase power-pulse spray. Resolution of symptoms and improvement in
      heart strain were achieved in all patients. There were no in-hospital
      mortalities. Complications occurred in 3 patients (20%), including 2 patients
      with acute tubular necrosis and 1 patient with an intraoperative cardiac arrest.
      Average hospitalization was 9 days (range: 4-26 days). All patients were
      discharged on full anticoagulation. None required supplemental oxygen at
      discharge. CONCLUSION: CDMT as primary treatment of MPE and SMPE has a high rate
      of technical and clinical success in a high-risk patient population. Experience
      and strict patient selection criteria may improve therapeutic outcomes.

PMID- 21885245
TI  - Bedside hand-carried ultrasound by internal medicine residents versus traditional
      clinical assessment for the identification of systolic dysfunction in patients
      admitted with decompensated heart failure.
AB  - BACKGROUND: The rapid detection of left ventricular systolic dysfunction (LVSD)
      is an important step in the clinical management of patients admitted with acute
      decompensated heart failure, because it allows the initiation of treatment
      specific to LVSD and avoidance of contraindicated therapies. The aim of this
      study was to determine whether internal medicine residents with limited
      ultrasound training could use hand-carried ultrasound (HCU) to identify LVSD.
      METHODS: Fifty patients admitted with acute decompensated heart failure were
      imaged from the parasternal window at the bedside with an HCU device by residents
      blinded to all clinical data, who had undergone limited cardiac ultrasound
      training (20 practice studies). Ejection fraction (EF) on HCU was graded as >40%
      or <40%. HCU EF and a number of physical exam findings and electrocardiographic
      and laboratory variables were compared for their ability to predict to formal
      echocardiographic left ventricular EF. RESULTS: The average formal EF was 32 +/-
      16% (range, 7%-70%), with 66% of patients having EFs < 40%. The residents'
      ability to detect an EF < 40% with HCU was excellent (sensitivity, 94%;
      specificity, 94%; negative predictive value, 88%; positive predictive value,
      97%). Binary logistic regression demonstrated that HCU EF was the most powerful
      predictor of EF < 40%, with minimal additional value from clinical, exam, lab,
      and electrocardiographic variables. The time interval between clinical assessment
      and availability of formal echocardiographic results was 22 +/- 17 hours.
      CONCLUSIONS: Residents with limited training in cardiac ultrasound were able to
      identify LVSD in patients with acute decompensated heart failure with superior
      accuracy compared with clinical, physical exam, lab, and electrocardiographic
      findings and an average of 22 hours before the results of formal echocardiography
      were available.

PMID- 21885246
TI  - Food quality, physical activity, and nutritional follow-up as determinant of
      weight regain after Roux-en-Y gastric bypass.
AB  - OBJECTIVE: Assess the lifestyle habits, including food patterns, of patients who
      underwent Roux-en-Y gastric bypass (RYGB) and to identify predictive factors in
      weight loss and regain. METHODS: Obese patients (100) who underwent RYGB from
      1998 to 2008 were included. Dietary habits were assessed by using 24 h dietary
      recall and the Food Frequency Questionnaire. Rates of weight regain and the
      percentage of excess weight loss (EWL) were calculated. Patients were also asked
      whether they attended nutritional follow-up visits after the operation and about
      the type and regularity of physical activities. RESULTS: The mean age was 45.1 +/
      9.9 y, and the majority of the patients were women (84%). Mean EWL was 59.1 +/-
      20.3%. Weight regain was seen in 56% of the patients with 29% of the patients
      having regained over 10.1% of the minimum weight reached after RYGB. Weight
      regain increased significantly with time after surgery (up to 2 y: 14.7%; from 2
      to 5 y: 69.7%; over 5 y: 84.8%). Poor diet quality characterized by excessive
      intake of calories, snacks, sweets, and fatty foods was statistically higher
      among those who regained weight. Sedentary lifestyle and lack of nutritional
      counseling follow-up were also significantly associated with regaining weight.
      CONCLUSION: Despite satisfactory results of EWL, the patients did not properly
      maintain the lost weight, mainly after 5 y postsurgery. Major factors that
      influenced this weight gain were poor diet quality, sedentary lifestyle, and lack
      of nutritional counseling follow-up.

PMID- 21885247
TI  - Sodium iodoacetate induced osteoarthrosis model in rabbit temporomandibular
      joint: CT and histological study (part I).
AB  - Studies to elucidate the pathophysiology of osteoarthrosis have been hampered by
      the lack of a rapid, reproducible animal model that mimics the histopathology and
      symptoms associated with the disease. The aim of this study is to evaluate the
      radiological, histological and histomorphometrical findings of four different
      concentrations of sodium iodoacetate (MIA) to create osteoarthrosis by using an
      arthrocentesis technique on rabbit temporomandibular joint (TMJ). 12 New Zealand
      white male rabbits received an injection of MIA (50 MUl dose of 1.5, 2, 2.5,
      3mg/ml concentrations) to a single joint of each group by arthrocentesis.
      Computed tomography (CT) images were obtained pre- and post-injections at 2, 4
      and 6 weeks. Early osteoarthritic changes in the rabbit TMJ were found
      histologically at 4 weeks and with a 3mg/ml concentration of MIA. The mean
      subchondral bone volume depended on the concentration of MIA and was 62+/-2.6%,
      63+/-4.1%, 42+/-3.6% and 38+/-3.8%, respectively. A minor abnormality was found
      on CT in six joints at the 4-week follow up. MIA injection and arthrocentesis
      offer a rapid and minimally invasive method of reproducing histologically
      osteoarthrotic lesions in the rabbit TMJ.

PMID- 21885248
TI  - Arthroscopic lysis and lavage in patients with temporomandibular anterior disc
      displacement without reduction.
AB  - The authors prospectively analysed 50 patients with chronic anterior disc
      displacement without reduction, who underwent arthroscopic lysis and lavage of
      the temporomandibular joint (TMJ). Patients with symptoms lasting less than 1
      year were assigned to Group A (n=28) and patients with symptoms lasting more than
      1 year to Group B (n=22). The most common problems were inflammatory changes of
      synovial and retrodiscal tissue (Group A, 71%; Group B, 82%). Fibrous adhesions
      were present in 14% of Group A patients and 45% of Group B patients. Degenerative
      changes of the disc and articular surface were present in 4% of Group A patients
      and 32% of Group B patients. Mouth opening increased 123% from baseline in Group
      A, and 112% in Group B (P<0.05). Pain decreased significantly in both groups
      (Group A, 2.5 points; Group B, 1.68 points; P<0.05). In conclusion, almost all
      patients with chronic anterior disc displacement without reduction benefited from
      arthroscopic lysis and lavage of the TMJ. Patients with a shorter duration of
      symptoms problems benefited more than those with a longer duration. Arthroscopic
      lysis and lavage of the TMJ is safe and beneficial in chronic anterior disc
      displacement without reduction.

PMID- 21885249
TI  - Customized titanium reconstruction of post-traumatic orbital wall defects: a
      review of 22 cases.
AB  - The authors present the clinical results of their method of customized
      reconstruction of orbital wall defects using titanium mesh or sheet. High
      resolution computed tomography (CT) data are imported and processed to create a
      three-dimensional (3D) image which is used to reconstruct the orbital defect.
      Mirror imaging of the air in the contralateral maxillary sinus is used to
      overcome artefact defects in the floor. A stereolithographic model is
      constructed, from which titanium mesh or sheet is shaped and sized to the
      required contours for implantation. Twenty-two patients were treated using this
      technique from 2003 to 2008. Postoperatively 10 patients reported early
      resolution of their diplopia. Six patients noticed significant improvement of
      their symptoms with mild residual diplopia in one direction only and at the
      extremes of gaze at final review. One patient required ocular muscle surgery.
      Enophthalmos resolved in eight of the nine cases. No patients developed
      enophthalmos or diplopia as a postoperative complication. The use of titanium
      mesh for orbital floor reconstruction has been shown to be safe and effective.
      Customized titanium implants accurately reproduce orbital contours thus restoring
      orbital volume. This reduces operative time and improves the functional and
      aesthetic outcomes of post-traumatic orbital reconstruction.

PMID- 21885250
TI  - High-sensitivity cardiac troponin T in essential hypertension.
AB  - BACKGROUND: Myocyte injury might be involved in the progression of essential
      hypertension (EHT) toward heart failure (HF). However, in the absence of high
      sensitivity (hs) assay, cardiac troponin T (TnT) in EHT has not been measurable.
      METHODS AND RESULTS: We studied 236 consecutive ambulatory patients (mean
      age=65.5 years; 110 men) with treated EHT (mean systolic blood pressure=134.3
      mmHg, mean serum N-terminal pro-B-type natriuretic peptide=86.6 pg/ml) for mean
      65.6 months. Patients with a history of HF were excluded. Single and multiple
      variable analyses were performed in search of clinical correlates of elevated hs
      TnT (>=0.003 ng/ml). Serum concentration of hs-TnT was >=0.003 ng/ml (mean=0.008
      ng/ml) in 184 patients. By single variable analysis, age, uric acid, log
      transformed N-terminal pro-B-type natriuretic peptide, brachial-ankle pulse wave
      velocity, Cornell electrocardiographic (ECG) voltage, and number of
      antihypertensive medications were associated with log-transformed hs-TnT, while
      hemoglobin and estimated glomerular filtration rate (eGFR) were inversely
      correlated with log-transformed hs-TnT. By multivariate analysis, age, eGFR and
      Cornell voltage were independent correlates of log-transformed hs-TnT, even after
      adjustment for clinical backgrounds including known prognostic biomarkers of EHT.
      CONCLUSIONS: hs-TnT was >=0.003 ng/ml in 78% of patients presenting with treated
      EHT and independently correlated with age, renal function, and ECG voltage of
      hypertrophy.

PMID- 21885251
TI  - Is the restricted ketogenic diet a viable alternative to the standard of care for
      managing malignant brain cancer?
AB  - Malignant brain cancer persists as a major disease of morbidity and mortality.
      The failure to recognize brain cancer as a disease of energy metabolism has
      contributed in large part to the failure in management. As long as brain tumor
      cells have access to glucose and glutamine, the disease will progress. The
      current standard of care provides brain tumors with access to glucose and
      glutamine. The high fat low carbohydrate ketogenic diet (KD) will target glucose
      availability and possibly that of glutamine when administered in carefully
      restricted amounts to reduce total caloric intake and circulating levels of
      glucose. The restricted KD (RKD) targets major signaling pathways associated with
      glucose and glutamine metabolism including the IGF-1/PI3K/Akt/Hif pathway. The
      RKD is anti-angiogenic, anti-invasive, anti-inflammatory, and pro-apoptotic when
      evaluated in mice with malignant brain cancer. The therapeutic efficacy of the
      restricted KD can be enhanced when combined with drugs that also target glucose
      and glutamine. Therapeutic efficacy of the RKD was also seen against malignant
      gliomas in human case reports. Hence, the RKD can be an effective non-toxic
      therapeutic option to the current standard of care for inhibiting the growth and
      invasive properties of malignant brain cancer.

PMID- 21885252
TI  - Versive seizures in occipital lobe epilepsy: lateralizing value and
      pathophysiology.
AB  - To clarify the value of versive seizures in lateralizing and localizing the
      epileptogenic zone in patients with occipital lobe epilepsy, we studied 13
      occipital lobe epilepsy patients with at least one versive seizure recorded
      during preoperative noninvasive video-EEG monitoring, who underwent occipital
      lobe resection, and were followed postoperatively for more than 2 years with
      Engel's class I outcome. The videotaped versive seizures were analyzed to compare
      the direction of version and the side of surgical resection in each patient.
      Moreover, we examined other motor symptoms (partial somatomotor manifestations
      such as tonic and/or clonic movements of face and/or limbs, automatisms, and
      eyelid blinking) associated with version. Forty-nine versive seizures were
      analyzed. The direction of version was always contralateral to the side of
      resection except in one patient. Among accompanying motor symptoms, partial
      somatomotor manifestations were observed in only five patients. In conclusion,
      versive seizure is a reliable lateralizing sign indicating contralateral
      epileptogenic zone in occipital lobe epilepsy. Since versive seizures were
      accompanied by partial somatomotor manifestations in less than half of the
      patients, it is suggested that the mechanism of version in occipital lobe
      epilepsy is different from that in frontal lobe epilepsy.

PMID- 21885253
TI  - What is the present-day EEG evidence for a preictal state?
AB  - EEG-based seizure prediction has undergone phases of optimism when analyses based
      on limited EEG samples suggested high sensitivity and specificity for several
      algorithms extracting features from raw preictal EEG data. When using long-term
      recordings, a more realistic view emerged which suggests that statistically
      significant predictions might be possible from surface and intracranial EEG, but
      no algorithm has yet demonstrated performance allowing for clinical application.
      Here, progress in EEG recording techniques, EEG analysis, and requirements for
      proper statistical validation of results are reported and discussed as they
      pertain to clinical implementation.

PMID- 21885254
TI  - Diffusion tensor imaging can localize the epileptogenic zone in nonlesional extra
      temporal refractory epilepsies when [(18)F]FDG-PET is not contributive.
AB  - Surgical outcome in patients with nonlesional refractory partial epilepsies could
      be improved by a more precise definition of the epileptogenic zone (EZ). The
      value of interictal FDG-PET hypometabolism, voxel-based-morphometry (VBM) and
      diffusion tensor imaging (DTI) is still debated. We compared the sensitivity and
      specificity of these noninvasive techniques in localizing the EZ with stereo
      electroencephalography (SEEG) results. Twenty patients with nonlesional partial
      epilepsy (13 temporal lobe epilepsy (TLE) and 7 extra-temporal (extra-TLE))
      underwent structural MRI, DTI and FDG-PET. FDG-PET was analyzed visually (vPET)
      blinded and unblinded and by statistical parametric mapping (SPM) (sPET).
      Individual modifications of grey matter volume and mean diffusivity increase were
      compared to a control group with SPM. The best sensitivity was provided by vPET
      unblinded (75%) and the best specificity (60%) by DTI. The sensitivity of vPET
      blinded (55%) was lower and those of sPET (40%) and VBM (35%) were still lower.
      In TLE, vPET analyzed either blinded or unblinded, performed the best and
      additional use of the other tools improved slightly the sensitivity. For extra
      TLE, combining vPET and DTI results increased the number of pertinent
      abnormalities detected especially for circumscribed changes in frontal lobe
      epilepsy (FLE). Combining vPET and DTI was the more efficient strategy for extra
      TLE, allowing the detection of pertinent abnormalities in FLE when FDG-PET alone
      was not contributive. Combining sPET or VBM with vPET was less useful.

PMID- 21885255
TI  - Transcranial direct current stimulation in refractory continuous spikes and waves
      during slow sleep: a controlled study.
AB  - Cathodal transcranial direct current stimulation (tDCS) decreases cortical
      excitability. The purpose of the study was to investigate whether cathodal tDCS
      could interrupt the continuous epileptiform activity. Five patients with focal,
      refractory continuous spikes and waves during slow sleep were recruited. Cathodal
      tDCS and sham stimulation were applied to the epileptic focus, before sleep (1
      mA; 20 min). Cathodal tDCS did not reduce the spike-index in any of the patients.

PMID- 21885256
TI  - Importance of genetic factors in the occurrence of epilepsy syndrome type: a twin
      study.
AB  - Although there is strong evidence that genetic factors contribute to risk for
      epilepsy, their role in the determination of syndrome type is less clear. This
      study was undertaken to address this question. Information related to epilepsy
      was obtained from twins included in 455 monozygotic and 868 dizygotic pairs
      ascertained from population-based twin registries in Denmark, Norway and the
      United States. Syndrome type was determined based on medical record information
      and detailed clinical interviews and classified using the International
      Classification Systems for the Epilepsies and Epileptic Syndromes. Concordance
      rates were significantly increased in monozygotic versus dizygotic pairs for all
      major syndrome groups except localization-related cryptogenic epilepsy. Among
      generalized epilepsies, genetic factors were found to play an important role in
      the determination of childhood absence, juvenile absence, juvenile myoclonic, and
      idiopathic generalized epilepsy; and to a lesser degree for epilepsies with grand
      mal seizures on awakening. Among localization-related epilepsies, genetic factors
      contributed to risk for localization-related idiopathic and symptomatic syndromes
      overall, but did not appear to play an important role in determining risk for
      frontal, occipital or temporal lobe epilepsy. These results suggest that, while
      genetic factors contribute to risk for major syndrome types, determined when
      possible, their contribution to risk for localization-related syndrome sub-types,
      as defined by specific focality, may be modest.

PMID- 21885258
TI  - Comparing the PANSS in Chinese and American inpatients: cross-cultural
      psychiatric analyses of instrument translation and implementation.
AB  - This article compares data from the Positive and Negative Syndrome Scale (PANSS)
      collected from Chinese and American inpatients diagnosed with schizophrenia to
      show how patterned differences in item ratings may reflect cultural attitudes of
      the raters. The Chinese sample (N=553) was based on consecutive admissions to
      four academic hospitals in Changsha, China. Only patients ill for 3 or more years
      were included in the analysis to match the chronically ill sample represented in
      the US CATIE sample. A total of 261 PANSS assessments were completed during a
      month when CATIE subjects had been hospitalized for 15 days or more to optimize
      equivalence of the US and Chinese samples. Controlling for age and gender, the
      total PANSS and the three sub-scores were all significantly lower in the Chinese
      than in the US CATIE sample by 5-8% (all p<.05). However, on 9 items, the Chinese
      sample scored 10-30% higher than the US sample (all p<.05) and on 5 items they
      scored over 20% higher (all p<.0001). These items rated increased hostility,
      poorer attention, lack of judgment and insight, disturbance of volition, and
      poorer impulse control. We ascribe these differences to cultural variations in
      the ways individuals relate to others in their social environment within Chinese
      and American societies.

PMID- 21885259
TI  - Safety analysis of liposomal amphotericin B in adult patients: anaemia,
      thrombocytopenia, nephrotoxicity, hepatotoxicity and hypokalaemia.
AB  - Liposomal amphotericin B (L-AmB), which was developed to reduce side effects, has
      been shown to have a better safety profile than both the deoxycholate and lipid
      complex forms of amphotericin B; however, the frequency of major side effects is
      still unclear. Thus, the aim of the present study was to assess retrospectively
      the frequency of L-AmB-induced anaemia, thrombocytopenia, nephrotoxicity,
      hepatotoxicity and hypokalaemia as well as the relationship between daily dose of
      L-AmB and these side effects. A low red blood cell (RBC) count (post-/pre
      treatment) and anaemia were observed in 7 and 10 of 21 adult patients,
      respectively. Thrombocytopenia was observed in 11 of 19 adult patients. Doses of
      L-AmB that are estimated to cause side effects of a low RBC count, anaemia and
      thrombocytopenia with 50% probability are 4.0, 3.3 and 3.0mg/kg/day,
      respectively. Nephrotoxicity was observed in 6 of 22 patients. Variations of
      total bilirubin, gamma-glutamyl transpeptidase, aspartate aminotransferase and
      alanine aminotransferase used as indices of hepatotoxicity were observed in 6, 7,
      8 and 8 of 22 patients, respectively. Hypokalaemia was observed in 4 of 9
      patients; however, nephrotoxicity, hepatotoxicity and hypokalaemia were not
      caused in a dose-dependent manner. In conclusion, the present analyses showed
      that L-AmB dose-dependently induced anaemia and thrombocytopenia in adult
      patients. It is important to pay attention to causing anaemia and
      thrombocytopenia when patients are receiving L-AmB at doses of >3.3mg/kg/day and
      >3.0mg/kg/day, respectively.

PMID- 21885257
TI  - Diffusion tensor imaging tractography of the optic radiation for epilepsy
      surgical planning: a comparison of two methods.
AB  - The optic radiation is a key white matter structure at risk during epilepsy
      surgery involving the temporal, parietal or occipital lobes. It shows
      considerable anatomical variability, cannot be delineated on clinical MRI
      sequences and damage may cause a disabling visual field deficit. Diffusion tensor
      imaging tractography allows non-invasive mapping of this pathway. Numerous
      methods have been published but direct comparison is difficult as patient,
      acquisition and analysis parameters differ. Two methods for delineating the optic
      radiation were applied to 6 healthy controls and 4 patients with epileptogenic
      lesions near the optic radiation. By comparing methods with the same datasets,
      many of the parameters could be controlled. The first method was previously
      developed to accurately identify Meyer's loop for planning anterior temporal lobe
      resection. The second aimed to address limitations of this method by using a more
      automated technique to reduce operator time and to depict the entire optic
      radiation. Whilst the core of the tract was common to both methods, there was
      significant variability between the methods. Method 1 gave a more consistent
      depiction of Meyer's loop with fewer spurious tracts. Method 2 gave a better
      depiction of the entire optic radiation, particularly in more posterior portions,
      but did not identify Meyer's loop in one patient. These results show that whilst
      tractography is a promising technique, there is significant variability depending
      on the method chosen even when the majority of parameters are fixed. Different
      methods may need to be chosen for surgical planning depending on the individual
      clinical situation.

PMID- 21885261
TI  - Enhanced transdermal delivery of indomethacin-loaded PLGA nanoparticles by
      iontophoresis.
AB  - Nanoparticles effectively deliver therapeutic agent by penetrating into the skin.
      Indomethacin (IM) and coumarin-6 were loaded in PLGA nanoparticles with an
      average diameter of 100 nm. IM and coumarin-6 were chosen as a model drug and as
      a fluorescent marker, respectively. The surfaces of the nanoparticles were
      negatively charged. Permeability of IM-loaded PLGA nanoparticles through rat skin
      was studied. Higher amount of IM was delivered through skin when IM was loaded in
      nanoparticles than IM was free molecules. Also, iontophoresis was applied to
      enhance the permeability of nanoparticles. When iontophoresis with 3 V/cm was
      applied, permeability of IM was much higher than that obtained by simple
      diffusion of nanoparticles through skin. The combination of charged nanoparticle
      system with iontophoresis is useful for effective transdermal delivery of
      therapeutic agents.

PMID- 21885260
TI  - Antibacterial effects of theaflavin and synergy with epicatechin against clinical
      isolates of Acinetobacter baumannii and Stenotrophomonas maltophilia.
AB  - Stenotrophomonas maltophilia and Acinetobacter baumannii are recognised as
      important nosocomial pathogens; however, due to their intrinsic resistance to
      multiple antibiotics, treatment options are limited. Polyphenols from black tea
      have been shown to possess antibacterial action. In this study, the antibacterial
      effects of various concentrations of theaflavin as well as combinations of
      theaflavin and epicatechin were determined using the disk diffusion assay. The
      results showed strong antibacterial activity of theaflavin against eight clinical
      isolates of S. maltophilia and A. baumannii. Significant synergy (P<=0.05) was
      also observed between theaflavin and epicatechin against all isolates. Although
      the mechanisms for this activity and synergy are not well understood, the
      clinical potential is clear and further research is recommended to determine the
      modes of action.

PMID- 21885262
TI  - Studies of the binding mechanism between aptamers and thrombin by circular
      dichroism, surface plasmon resonance and isothermal titration calorimetry.
AB  - Thrombin, a multifunctional serine protease, has both procoagulant and
      anticoagulant functions in human blood. Thrombin has two electropositive
      exosites. One is the fibrinogen-binding site and the other is the heparin-binding
      site. Over the past decade, two thrombin-binding aptamers (15-mer and 29-mer)
      were reported by SELEX technique. Recently, many studies examined the
      interactions between the 15-mer aptamer and thrombin extensively, but the data on
      the difference of these two aptamers binding to thrombin are still lacking and
      worth investigating for fundamental understanding. In the present study, we
      combined conformational data from circular dichroism (CD), kinetics and
      thermodynamics information from surface plasmon resonance (SPR) and isothermal
      titration calorimetry (ITC) to compare the binding mechanism between the two
      aptamers with thrombin. Special attentions were paid to the formation of G
      quadruplex and the effects of ions on the aptamer conformation on the binding and
      the kinetics discrimination between specific and nonspecific interactions of the
      binding. The results indicated reasonably that the 15-mer aptamer bound to
      fibrinogen-binding site of thrombin using a G-quadruplex structure and was
      dominated by electrostatic interactions, while the 29-mer aptamer bound to
      heparin-binding site thrombin using a duplex structure and was driven mainly by
      hydrophobic effects.

PMID- 21885263
TI  - [Neonatal atrial tachycardia: suggestive clinical sign of Costello syndrome].
AB  - Costello syndrome is a rare association of symptoms caused by de novo germline
      mutations of the HRAS oncogene interfering in the RAS/mitogen-activated protein
      kinase (MAPK) signal transduction pathway. Mutations in this pathway are also
      responsible for Noonan syndrome and the related cardiofaciocutaneous syndrome
      (CFC) as well as LEOPARD syndrome. The 4 syndromes share phenotypic resemblances
      concerning patients' morphology but also regarding associated cardiac disease,
      namely hypertrophic cardiomyopathy, pulmonary stenosis, and atrial septal defect.
      The electrocardiogram often shows an upper deviation of the QRS axis. Arrhythmias
      are rare but, if present, are particularly typical of CS. We describe herein two
      newborn infants with Costello syndrome revealed by atrial tachycardia associated
      with characteristic morphological and cardiac features of syndromes related to
      mutations in the RAS/MAPK pathway.

PMID- 21885264
TI  - [Neonatal intoxication with pyrimethamine: risk due to the absence of pediatric
      formulation?].
AB  - Curative treatment of congenital toxoplasmosis is based on the association of
      pyrimethamine and sulfonamide. There is currently no pediatric galenic
      formulation. We report the case of a newborn child affected by asymptomatic
      congenital toxoplasmosis who received an overdose of pyrimethamine. The patient
      received a dose of pyrimethamine 4 times, equal to 100 times the recommended
      dose, due to an error in the prescription. He had partial seizures 48 h after the
      last medicinal absorption. We noted a lack of appetite and vomiting, with a
      favorable progression in 5 days. Blood analysis showed isolated, spontaneously
      regressive moderate cholestasis. We propose a pharmacological clarification on
      the treatment of congenital toxoplasmosis.

PMID- 21885265
TI  - Glucose supplement reverses the fasting-induced suppression of cellular immunity
      in Mongolian gerbils (Meriones unguiculatus).
AB  - Glucose plays an important role in immunity. Three day fasting will decrease
      cellular immunity and blood glucose levels in Mongolian gerbils (Meriones
      unguiculatus). In the present study, we tested the hypothesis that glucose
      supplement can reverse the fasting-induced suppression in cellular immunity in
      gerbils. Twenty-eight male gerbils were selected and randomly divided into fed
      and fasting groups. Half of the gerbils in each group were then provided with
      either 10% glucose water or pure water. After 66 h, each gerbil was injected with
      phytohaemagglutinin (PHA) solution to challenge cellular immunity. Results showed
      that glucose supplement restored blood glucose levels in fasted gerbils to those
      of the fed controls. It also recovered cellular immunity, body fat mass and serum
      leptin levels in fasted gerbils to the values of the fed controls. Blood glucose
      levels were positively correlated with body fat mass, leptin levels and cellular
      immune responses. Thymus and spleen masses, and white blood cells in fasted
      gerbils were not affected by glucose supplement. In general, our data demonstrate
      that glucose supplement could reverse fasting-induced suppression of cellular
      immunity in Mongolian gerbils.

PMID- 21885266
TI  - Lipopolysaccharides induce changes in the visceral pigmentation of Eupemphix
      nattereri (Anura: Leiuperidae).
AB  - Amphibians have an extracutaneous pigmentary system composed of melanin
      containing cells in various tissues and organs. The functional role of these
      pigment cells in visceral organs has not yet been determined, although several
      hypotheses have been proposed. Our aim was to describe the visceral pigmentation
      in the frog Eupemphix nattereri under conditions of endotoxemia induced
      experimentally with lipopolysaccharides (LPS) from Escherichia coli and to
      analyze the pigmentation on the organs' surface. We used 60 adult males of E.
      nattereri and analyzed the visceral pigmentation 2 (LPS 2h), 6 (LPS 6h), 12 (LPS
      12h), 24 (LPS 24h) or 48 h (LPS 48 h) after the LPS inoculation. We observed
      pigmentation on the surface of several abdominal organs. The highest degree of
      pigmentation was found only on the testes of the animals in the LPS 2h, LPS 6h
      and LPS 12h groups. The pigmentation decreased in the animals of the LPS 24h and
      LPS 48 h groups. The LPS administration produced no changes in the pigmentation
      of the cardio-respiratory and digestive systems. Thus, the cells appear to have
      responded to LPS intoxication, producing a rapid increase of pigmentation on the
      surface of the testes and a subsequent decrease in the pigmentation. These
      changes are most likely related to the bactericidal role of melanin, which
      neutralizes the effects of LPS.

PMID- 21885267
TI  - Cloning, expression of a peroxiredoxin gene from Acinetobacter sp. SM04 and
      characterization of its recombinant protein for zearalenone detoxification.
AB  - Zearalenone (ZEN) is a Fusarium mycotoxin, which has been associated with
      hyperestrogenism and other reproductive disorders in farm animals. ZEN
      contaminated grains as well as its by-products had engendered numerous economic
      losses to farm animals' production, so the detoxification of ZEN-contaminated
      grains and its by-products would be necessary and beneficial. In this study, a
      peroxiredoxin (Prx) gene from Acinetobacter sp. SM04 was cloned, and over
      expressed in Escherichia coli BL21 (DE3). The Prx gene of Acinetobacter sp. SM04
      encodes a protein of 187 amino acids residues and NCBI BLAST program analysis of
      deduced amino acids shows high identity with 2-Cys Prx family. Interestingly,
      recombinant Prx show efficient ability to degrade ZEN using H(2)O(2). Results of
      MCF-7 cell proliferation assay also found ZEN were oxidized into little
      estrogenic metabolites by purified recombinant Prx plus H(2)O(2). Further, model
      experiments on decontamination of ZEN-contaminated corn using recombinant Prx
      were performed, and results found nearly 90% of ZEN was degraded when crushed ZEN
      contaminated corn samples (nearly 1,000 MUg ZEN per kg grain) were treated with
      purified recombinant Prx plus 0.09% (m/m) H(2)O(2) for 6h at 30 degrees C. In
      addition, the optimum pH and temperature of purified recombinant Prx for ZEN
      degradation were 9.0 and 70 degrees C respectively.

PMID- 21885268
TI  - cDNA cloning, characterization and expression analysis of a novel antimicrobial
      peptide gene penaeidin-3 (Fi-Pen3) from the haemocytes of Indian white shrimp
      Fenneropenaeus indicus.
AB  - A new member of antimicrobial peptide genes of the penaeidin family, penaeidin 3,
      was cloned from the haemocytes of Indian white shrimp Fenneropeneaus indicus (F.
      indicus), by reverse transcription PCR (RT-PCR) and rapid amplification of cDNA
      end (RACE-PCR) methods. The complete nucleotide sequence of cDNA clone of Indian
      white shrimp F. indicus Penaeidin 3 (Fi-Pen3) was 243bp long and has an open
      reading frame which encodes 80 amino acid peptide. The homology analysis of Fi
      Pen3 sequence with other Penaeidins 3 shows higher similarity with Penaeus
      monodon (92%). The theoretical 3D structure generated through ab initio modelling
      indicated the presence of two-disulphide bridges in the alpha-helix. The signal
      peptide sequence of Fi-Pen3 is almost entirely homologous to that of other
      Penaeidin 3 of crustaceans, while differing relatively in the N-terminal domain
      of the mature peptide. The mature peptide has a predicted molecular weight of
      84.9kDa, and a theoretical pI of 9.38. Phylogenetic analysis of Fi-Pen3 shows
      high resemblance with other Pen-3 from P. monodon, Litopenaeus stylirostris,
      Litopenaeus vannamei and Litopenaeus setiferus. Fi-Pen3 found to be expressed in
      haemocytes, heart, hepatopancreas, muscles, gills, intestine, and eyestalk with
      higher expression in haemocytes. Microbial challenge resulted in mRNA up
      regulation, up to 6h post injection of Vibrio parahemolyticus. The Fi-Pen3 mRNA
      expression of F. indicus in the premolt stage (D(01) and D(02)) was significantly
      up-regulated than the postmolt (A and B) and intermolt stages (C). The findings
      of the present paper underline the involvement of Fi-Pen3 in innate immune system
      of F. indicus.

PMID- 21885269
TI  - Heart arachidonic acid is uniquely sensitive to dietary arachidonic acid and
      docosahexaenoic acid content in domestic piglets.
AB  - This study determined the sensitivity of heart and brain arachidonic acid (ARA)
      and docosahexaenoic acid (DHA) to the dietary ARA level in a dose-response design
      with constant, high DHA in neonatal piglets. On day 3 of age, pigs were assigned
      to 1 of 6 dietary formulas varying in ARA/DHA as follows (% fatty acid, FA/FA):
      (A1) 0.1/1.0; (A2) 0.53/1.0; (A3-D3) 0.69/1.0; (A4) 1.1/1.0; (D2) 0.67/0.62; and
      (D1) 0.66/0.33. At necropsy (day 28) higher levels of dietary ARA were associated
      with increased heart and liver ARA, while brain ARA remained unaffected. Dietary
      ARA had no effect on tissue DHA accretion. Heart was particularly sensitive, with
      pigs in the intermediate groups having different ARA (A2, 18.6+/-0.7%; A3, 19.4+/
      1.0%) and a 0.17% increase in dietary ARA resulted in a 0.84% increase in heart
      ARA. Further investigations are warranted to determine the clinical significance
      of heart ARA status in developing neonates.

PMID- 21885271
TI  - Street-level policing in the Downtown Eastside of Vancouver, Canada, during the
      2010 Winter Olympics.
AB  - BACKGROUND: Police presence within street-based drug scenes has the potential to
      disrupt injection drug users' (IDUs) access to health services and prompt
      increased injection-related risk behaviour. We examined street-level policing in
      the Downtown Eastside (DTES) of Vancouver during the Olympic Winter games, to
      assess the potential impact on access to harm reduction services and injection
      related risk behaviour. METHODS: We analysed data from observational activities
      documenting police and drug user behaviour, unstructured interviews with drug
      users in street settings (n=15), expert interviews with legal and health
      professionals (n=6), as well as utilisation statistics from a local supervised
      injection facility (SIF). RESULTS: Although police presence was elevated within
      the DTES during the Olympics, there was little evidence to suggest that police
      activities influenced IDUs' access to health services or injection-related risk
      behaviour. SIF attendance during the Olympics was consistent with regular monthly
      patterns. CONCLUSION: Police presence during the Olympics did not reduce access
      to health services amongst local IDUs or prompt increased injection-related risk
      behaviour. Increased cooperation between local law enforcement and public health
      bodies likely offset the potential for negative health consequences resulting
      from police activity.

PMID- 21885270
TI  - Orientation and function of the nuclear-centrosomal axis during cell migration.
AB  - A hallmark of polarity in most migrating cells is the orientation of the nuclear
      centrosomal (NC) axis relative to the front-back cellular axis. Here, we review
      'effector functions' associated with the NC axis during cell migration. We
      highlight recent research that has demonstrated that the orientation of the NC
      axis depends upon the coordinated, but separate positioning of the nucleus and
      the centrosome. We stress the importance of environmental factors such as cell
      cell contacts and substrate topology for NC axis orientation. Finally, we
      summarize tests of the significance of this axis for cell migration and disease.

PMID- 21885272
TI  - Thermal decomposition of electronic wastes: mobile phone case and other parts.
AB  - Pyrolysis and combustion runs at 850 degrees C in a horizontal laboratory furnace
      were carried out on different parts of a mobile phone (printed circuit board,
      mobile case and a mixture of both materials). The analyses of the carbon oxides,
      light hydrocarbons, polycyclic aromatic hydrocarbons (PAHs), polychlorodibenzo-p
      dioxin, polychlorodibenzofurans (PCDD/Fs), and dioxin-like PCBs are shown.
      Regarding semivolatile compounds, phenol, styrene, and its derivatives had the
      highest yields. In nearly all the runs the same PAHs were identified, naphthalene
      being the most common component obtained. Combustion of the printed circuit board
      produced the highest emission factor of PCDD/Fs, possibly due to the high copper
      content.

PMID- 21885273
TI  - Design, synthesis and anticancer activity of novel dihydrobenzofuro[4,5
      b][1,8]naphthyridin-6-one derivatives.
AB  - On the basis of the chemical structures of psorospermin with a xanthone template
      and acronycine derivatives with an acridone template, rac-1 and rac-2 constructed
      on an 1,2-dihydrobenzofuro[4,5-b][1,8]naphthyridin-6(11H)-one scaffold were
      designed and synthesized as potential anticancer agents. Their anticancer
      activities were evaluated against five human cancer cell lines. Rac-2 showed
      similar anticancer activity to doxorubicin and rac-1 exhibited even higher
      anticancer activity against LNCaP (IC(50)=0.14 MUM), DU145 (IC(50)=0.15 MUM), PC3
      (IC(50)=0.30 MUM) and MCF-7 (IC(50)=0.26 MUM) cancer lines than doxorubicin and
      rac-2. Also, rac-1 revealed very potent anticancer activity (IC(50)=0.15 MUM)
      against MCF-7/ADR cell (doxorubicin-resistant breast cancer cell) lines and
      induced G2/M phase arrest of the cell cycle in MCF-7/ADR cells.

PMID- 21885274
TI  - Synthesis and antigastric ulcer activity of novel 5-isoproyl-3,8-dimethylazulene
      derivatives.
AB  - 5-Isoproyl-3,8-dimethylazulene derivatives were synthesized and evaluated for
      antigastric ulcer activity in vivo. Some of them possess the best activity
      against gastric ulcer with ulcer index values lower than the drug reference
      (omeprazole). The structure-activity relationship (SAR) shows that the lipophilic
      flat structure contributes to quite potent antigastric ulcer activity.

PMID- 21885275
TI  - Discovery of PF-184563, a potent and selective V1a antagonist for the treatment
      of dysmenorrhoea. The influence of compound flexibility on microsomal stability.
AB  - The V1a receptor has emerged as an attractive target for a range of indications
      including Raynaud's disease and dysmenorrhoea. As part of an effort to discover a
      new class of orally active V1a antagonist, we optimised a highly lipophilic,
      metabolically unstable lead into a range of potent, selective and metabolically
      stable V1a antagonists. In this communication, we demonstrate the series
      dependent effect of limiting the number of rotatable bonds in order to decrease
      Cytochrome P450-mediated metabolism. This effort culminated in the discovery of
      PF-184563, a novel, selective V1a antagonist with excellent in vitro and in vivo
      properties.

PMID- 21885276
TI  - Design, synthesis and structure-activity relationship of novel [3.3.1] bicyclic
      sulfonamide-pyrazoles as potent gamma-secretase inhibitors.
AB  - The structure-activity relationship (SAR) of a novel, potent and metabolically
      stable series of sulfonamide-pyrazoles that attenuate beta-amyloid peptide
      synthesis via gamma-secretase inhibition is detailed herein. Sulfonamide
      pyrazoles that are efficacious in reducing the cortical Abetax-40 levels in FVB
      mice via a single PO dose, as well as sulfonamide-pyrazoles that exhibit
      selectivity for inhibition of APP versus Notch processing by gamma-secretase, are
      highlighted.

PMID- 21885277
TI  - Discovery of a highly potent series of TLR7 agonists.
AB  - The discovery of a series of highly potent and novel TLR7 agonist interferon
      inducers is described. Structure-activity relationships are presented, along with
      pharmacokinetic studies of a lead molecule from this series of N9-pyridylmethyl-8
      oxo-3-deazapurine analogues. A rationale for the very high potency observed is
      offered. An investigation of the clearance mechanism of this class of compounds
      in rat was carried out, resulting in aldehyde oxidase mediated oxidation being
      identified as a key component of the high clearance observed. A possible solution
      to this problem is discussed.

PMID- 21885278
TI  - Synthesis of beta-functionalized temoporfin derivatives for an application in
      photodynamic therapy.
AB  - The synthesis of novel beta-functionalized derivatives of the clinically used
      photosensitizer Temoporfin has been achieved by nucleophilic addition reactions
      to a corresponding diketo chlorin. The beta-substituted dihydroxychlorin products
      exhibit a strong absorption in the red spectral region, a high singlet oxygen
      quantum yield, and were found to be highly effective in in vitro assays against
      HT-29 tumor cells.

PMID- 21885279
TI  - Sulfonamides as selective oestrogen receptor beta agonists.
AB  - A series of p-hydroxybenzenesulphonamides ERbeta receptor agonists were
      discovered and several compounds identified had excellent selectivity over the
      related ERalpha receptor. One of these, compound 11, had an interesting binding
      conformation determined by X-ray and represents an excellent starting point in
      the quest for further selective ERbeta agonists.

PMID- 21885280
TI  - Synthesis and evaluation of 1-(4-[18F]fluoroethyl)-7-(4'-methyl)curcumin with
      improved brain permeability for beta-amyloid plaque imaging.
AB  - Alzheimer's disease is characterized by the accumulation of beta-amyloid (Abeta)
      plaques and neurofibrillary tangles (NFTs) in the brain. We previously developed
      [(18)F]fluoropropylcurcumin ([(18)F]FP-curcumin), which demonstrated excellent
      binding affinity (K(i)=0.07 nM) for Abeta(1-40) aggregates and good
      pharmacokinetics in normal mouse brains. However, its initial brain uptake was
      poor (0.52% ID/g at 2 min post-injection). Therefore, in the present study,
      fluorine-substituted 4,4'-bissubstituted or pegylated curcumin derivatives were
      synthesized and evaluated. Their binding affinities for Abeta(1-42) aggregates
      were measured and 1-(4-fluoroethyl)-7-(4'-methyl)curcumin (1) had the highest
      binding affinity (K(i)=2.12 nM). Fluorescence staining of Tg APP/PS-1 mouse brain
      sections demonstrated high and specific labeling of Abeta plaques by 1 in the
      cortex region, which was confirmed with thioflavin-S staining of the same spots
      in the adjacent brain sections. Radioligand [(18)F]1 was found to have an
      appropriate partition coefficient (logP(o/w)=2.40), and its tissue distribution
      in normal mice demonstrated improved brain permeability (1.44% ID/g at 2 min post
      injection) compared to that of [(18)F]FP-curcumin by a factor of 2.8 and fast
      wash-out from mouse brains (0.45% ID/g at 30 min post-injection). These results
      suggest that [(18)F]1 may hold promise as a PET radioligand for Abeta plaque
      imaging.

PMID- 21885281
TI  - Intraoperative assessment of surgical margins during breast conserving surgery of
      ductal carcinoma in situ by use of radiofrequency spectroscopy.
AB  - Assessment of margins when excising ductal carcinoma in situ (DCIS) of the breast
      is difficult. Frozen section is unreliable and specimen intraoperative
      radiography only provides information regarding the extent of the visualized
      lesion or the microcalcifications. A multi-center, single arm study was conducted
      to evaluate the benefit of a novel device (MarginProbe) in intraoperative margin
      assessment during breast conserving surgery (BCS) of DCIS, and the associated
      reduction of re-excisions. We present results for 22 patients, from those
      enrolled in our institution. The device was used as an adjunctive tool to current
      practice. Based on permanent histology reporting, the rate of successful
      procedures was 86%. The improvement in intraoperative assessment with device use
      was associated with a reduction in re-excision rates, from 38.8 to 18%.

PMID- 21885282
TI  - Kif18A uses a microtubule binding site in the tail for plus-end localization and
      spindle length regulation.
AB  - The mitotic spindle is a macromolecular structure utilized to properly align and
      segregate sister chromatids to two daughter cells. During mitosis, the spindle
      maintains a constant length, even though the spindle microtubules (MTs) are
      constantly undergoing polymerization and depolymerization [1]. Members of the
      kinesin-8 family are important for the regulation of spindle length and for
      chromosome positioning [2-9]. Kinesin-8 proteins are length-specific, plus-end
      directed motors that are proposed to be either MT depolymerases [3, 4, 8, 10, 11]
      or MT capping proteins [12]. How Kif18A uses its destabilization activity to
      control spindle morphology is not known. We found that Kif18A controls spindle
      length independently of its role in chromosome positioning. The ability of Kif18A
      to control spindle length is mediated by an ATP-independent MT binding site at
      the C-terminal end of the Kif18A tail that has a strong affinity for MTs in vitro
      and in cells. We used computational modeling to ask how modulating the motility
      or binding properties of Kif18A would affect its activity. Our modeling predicts
      that both fast motility and a low off rate from the MT end are important for
      Kif18A function. In addition, our studies provide new insight into how
      depolymerizing and capping enzymes can lead to MT destabilization.

PMID- 21885284
TI  - Interhemispheric connections shape subjective experience of bistable motion.
AB  - The right and left visual hemifields are represented in different cerebral
      hemispheres and are bound together by connections through the corpus callosum.
      Much has been learned on the functions of these connections from split-brain
      patients [1-4], but little is known about their contribution to conscious visual
      perception in healthy humans. We used diffusion tensor imaging and functional
      magnetic resonance imaging to investigate which callosal connections contribute
      to the subjective experience of a visual motion stimulus that requires
      interhemispheric integration. The "motion quartet" is an ambiguous version of
      apparent motion that leads to perceptions of either horizontal or vertical motion
      [5]. Interestingly, observers are more likely to perceive vertical than
      horizontal motion when the stimulus is presented centrally in the visual field
      [6]. This asymmetry has been attributed to the fact that, with central fixation,
      perception of horizontal motion requires integration across hemispheres whereas
      perception of vertical motion requires only intrahemispheric processing [7]. We
      are able to show that the microstructure of individually tracked callosal
      segments connecting motion-sensitive areas of the human MT/V5 complex (hMT/V5+;
      [8]) can predict the conscious perception of observers. Neither connections
      between primary visual cortex (V1) nor other surrounding callosal regions exhibit
      a similar relationship.

PMID- 21885283
TI  - Distinct roles for F-BAR proteins Cdc15p and Bzz1p in actin polymerization at
      sites of endocytosis in fission yeast.
AB  - BACKGROUND: Genetic analyses of budding and fission yeast identified >50 proteins
      that assemble at sites of clathrin-mediated endocytosis in structures called
      actin patches. These proteins include clathrin, clathrin-interacting proteins,
      actin binding proteins, and peripheral membrane proteins such as F-BAR proteins.
      Many questions remain regarding the interactions of these proteins, particularly
      the participation of F-BAR proteins in the assembly of actin filaments. RESULTS:
      Our microscopic and genetic interaction experiments on fission yeast show that F
      BAR proteins Cdc15p and Bzz1p accumulate in two distinct zones on invaginating
      membrane tubules and interact with Myo1p and Wsp1p, nucleation-promoting factors
      for Arp2/3 complex. The two F-BAR proteins peak prior to movement of the actin
      patch and their accumulation in actin patches depends on the nucleation-promoting
      factors. At their peak local concentrations, we estimated the stoichiometries of
      the proteins in actin patches to be one Bzz1p per two Wsp1p and one Cdc15p per
      Myo1p. Purified Bzz1p has two SH3 domains that interact with Wsp1p and stimulate
      actin polymerization by Arp2/3 complex. Cells lacking either Cdc15p or Bzz1p
      assemble 3- to 5-fold less actin in patches (in spite of normal levels of Wsp1p,
      Myo1p, and Arp2/3 complex), and patches move shorter distances from the plasma
      membrane. CONCLUSION: We propose that during clathrin-mediated endocytosis, F-BAR
      proteins interact with nucleation-promoting factors to stimulate Arp2/3 complex
      in two different zones along the invaginating tubule. We further propose that
      polymerization of actin filaments in these two zones contributes to membrane
      scission.

PMID- 21885286
TI  - A descriptive study of patient satisfaction and the structural factors of
      Norwegian intensive care nursing.
AB  - PURPOSE: The aim of this study was to describe patient satisfaction with nursing
      care in three different Norwegian Coronary Intensive Care Units and compare the
      results with other structural factors such as nursing competence, skill-mix,
      clinical experience, nurse to patient ratio and number of beds. METHODS: A
      descriptive and comparative design was employed and 150 patients at three
      Coronary Intensive Care Units were included. Patient satisfaction data was
      collected using the Intensive Nursing Care Quality Instrument (59 items). The
      data collected was comprised of two parts: a questionnaire and information on the
      structural factors of the organisational structure. The data was analysed using
      descriptive statistics. RESULTS: Patients expressed overall satisfaction with the
      nursing care. No clear association was found between patient satisfaction and
      nursing competence, skill-mix, clinical experience, nurse to patient ratio and
      number of beds. When comparing results between units, significant differences
      were seen for 17 out of 46 questions. CONCLUSIONS: The results provide insight
      into how critical care staffing and skill-mix affect patient satisfaction and
      guide future nursing research in this subject area.

PMID- 21885285
TI  - Molecular organization of Drosophila neuroendocrine cells by Dimmed.
AB  - BACKGROUND: In Drosophila, the basic-helix-loop-helix protein DIMM coordinates
      the molecular and cellular properties of all major neuroendocrine cells,
      irrespective of the secretory peptides they produce. When expressed by
      nonneuroendocrine neurons, DIMM confers the major properties of the regulated
      secretory pathway and converts such cells away from fast neurotransmission and
      toward a neuroendocrine state. RESULTS: We first identified 134 transcripts
      upregulated by DIMM in embryos and then evaluated them systematically using
      diverse assays (including embryo in situ hybridization, in vivo chromatin
      immunoprecipitation, and cell-based transactivation assays). We conclude that of
      eleven strong candidates, six are strongly and directly controlled by DIMM in
      vivo. The six targets include several large dense-core vesicle (LDCV) proteins,
      but also proteins in non-LDCV compartments such as the RNA-associated protein
      Maelstrom. In addition, a functional in vivo assay, combining transgenic RNA
      interference with MS-based peptidomics, revealed that three DIMM targets are
      especially critical for its action. These include two well-established LDCV
      proteins, the amidation enzyme PHM and the ascorbate-regenerating electron
      transporter cytochrome b(561-1). The third key DIMM target, CAT-4 (CG13248), has
      not previously been associated with peptide neurosecretion-it encodes a putative
      cationic amino acid transporter, closely related to the Slimfast arginine
      transporter. Finally, we compared transcripts upregulated by DIMM with those
      normally enriched in DIMM neurons of the adult brain and found an intersection of
      18 DIMM-regulated genes, which included all six direct DIMM targets. CONCLUSIONS:
      The results provide a rigorous molecular framework with which to describe the
      fundamental regulatory organization of diverse neuroendocrine cells.

PMID- 21885287
TI  - Biochemical characterization of a novel type-II VEGFR2 kinase inhibitor:
      comparison of binding to non-phosphorylated and phosphorylated VEGFR2.
AB  - A pyrrolo[3,2-d]pyrimidine-based type-II vascular endothelial growth factor
      receptor 2 (VEGFR2) kinase inhibitor, compound 20d, displayed time-dependent
      inhibition of the non-phosphorylated catalytic domain of VEGFR2. In contrast, 20d
      did not show time-dependent inhibition of the phosphorylated enzyme. Dissociation
      of 20d from non-phosphorylated VEGFR2 was slow and the half-life of the complex
      was longer than 4h. In contrast, dissociation of 20d from the phosphorylated
      enzyme was very fast (half-life <5min). A fluorescent tracer based displacement
      assay and surface plasmon resonance (SPR) analysis confirmed the slow
      dissociation of 20d from only non-phosphorylated VEGFR2. Thus, activity based and
      binding kinetic analyses both supported slow dissociation of 20d from only non
      phosphorylated VEGFR2. Additionally SPR analysis revealed that association rates
      were rapid and nearly identical for these two phosphorylation forms of VEGFR2.
      From these results, the preferential effect of 20d on non-phosphorylated VEGFR2
      is dominated by its slow dissociation from the enzyme and this characteristically
      long residence time may increase its potency in vivo. The present findings may
      assist in the design of novel type-II kinase inhibitors.

PMID- 21885288
TI  - Design and synthesis of new prostaglandin D2 receptor antagonists.
AB  - To identify new cost-effective prostaglandin D2 (DP) receptor antagonists, a
      series of novel 3-benzoylaminophenylacetic acids were synthesized and
      biologically evaluated. Among those tested, some representative compounds were
      found to be orally available. Receptor selectivity and rat PK profiles were also
      evaluated. The structure-activity relationship (SAR) study is presented.

PMID- 21885289
TI  - Antifungal thiopeptide cyclothiazomycin B1 exhibits growth inhibition
      accompanying morphological changes via binding to fungal cell wall chitin.
AB  - Cyclothiazomycin B1 (CTB1) is an antifungal cyclic thiopeptide isolated from the
      culture broth of Streptomyces sp. HA 125-40. CTB1 inhibited the growth of several
      filamentous fungi including plant pathogens along with swelling of hyphae and
      spores. The antifungal activity of CTB1 was weakened by hyperosmotic conditions,
      and hyphae treated with CTB1 burst under hypoosmotic conditions, indicating
      increased cell wall fragility. CTB1-sensitive fungal species contain high levels
      of cell wall chitin and/or chitosan. Unlike nikkomycin Z, a competitive inhibitor
      of chitin synthase (CHS), CTB1 did not inhibit CHS activity. Although CTB1
      inhibited CHS biosynthesis, the same result was also obtained with a non-specific
      proteins inhibitor, cycloheximide, which did not reduce cell wall rigidity. These
      results indicate that the primary target of CTB1 is not CHS, and we concluded
      that CTB1 antifungal activity was independent of this sole inhibition. We found
      that CTB1 bound to chitin but did not bind to beta-glucan and chitosan. The
      results of the present study suggest that CTB1 induces cell wall fragility by
      binding to chitin, which forms the fungal cell wall. The antifungal activity of
      CTB1 could be explained by this chitin-binding ability.

PMID- 21885290
TI  - Natural daucane sesquiterpenes with antiproliferative and proapoptotic activity
      against human tumor cells.
AB  - Plants of the genera Ferula and Ferulago are known for their complex content in
      bioactive secondary metabolites such as coumarins, phenylpropanoids, and
      sesquiterpenes. We used the ground parts of Ferula communis subsp. communis,
      Ferula glauca subsp. glauca and Ferulago campestris as natural sources for the
      isolation of four coumarins (CU-1 to CU-4), two phenylpropanoids (PE-1 and PE-2),
      one polyacetylene (PA-1) and 16 daucane esters (DE-1 to DE-16). The cytotoxic
      activity of the isolated compounds was evaluated against a panel of seven human
      tumor cell lines. Fourteen of the daucane derivatives showed antiproliferative
      activity at least against one of the human tumor cell lines tested, four
      compounds (DE-5, DE-8, DE-11, and DE-16) were active against all the tested cell
      lines. Among them DE-11 was the most cytotoxic compound against HeLa (4.4 +/- 0.7
      MUM), A549 (2.8 +/- 1.4 MUM), HL-60 (2.6 +/- 0.4 MUM), K562 (26.5 +/- 6.0 MUM) RS
      4;11 (1.7 +/- 0.3 MUM) and SEM (2.4 +/- 0.1 MUM) cell lines, while DE-8 was the
      most active against Jurkat (3.3 +/- 0.8 MUM). Preliminary structure-activity
      relationship suggests that the most active compounds in the daucane series
      present the trans fusion of the penta- and hepta-atomic cycles, and lipophylic
      ester groups linked to position 6. Isomeric derivatives such as DE-8 and DE-9 or
      DE-3, DE-4, and DE-5 exhibited significant differences in their IC(50) supporting
      that the beta orientation for the ester group in the position 2 enhances the
      cytotoxic activity. Furthermore, the pro-apoptotic effect of the most active
      compounds evaluated in Jurkat cell line showed that these compounds are able to
      induce apoptosis in a time and concentration-dependent manner. Our findings
      suggest the potential role of daucane derivatives as models for the development
      of proapoptotic compounds.

PMID- 21885292
TI  - Endoscopically-assisted subcondylar and vertical ramus osteotomies for the
      treatment of symmetrical mandibular prognathism.
AB  - The author describe the endoscopically-assisted intraoral vertical ramus (IVRO)
      and subcondylar (ISCO) osteotomies for the treatment of symmetric mandibular
      prognathism. The use of the saw and the bone chisel under the continuous control
      of the endoscope provides a safer approach since the osteotomy is controlled
      during the whole process. The introduction of the endoscope to provide complete
      visualization of the osteotomy site may overcome the traditional limitations of
      direct visualization in IVRO and ISCO.

PMID- 21885291
TI  - Structure of the adenosine A(2A) receptor in complex with ZM241385 and the
      xanthines XAC and caffeine.
AB  - Methylxanthines, including caffeine and theophylline, are among the most widely
      consumed stimulant drugs in the world. These effects are mediated primarily via
      blockade of adenosine receptors. Xanthine analogs with improved properties have
      been developed as potential treatments for diseases such as Parkinson's disease.
      Here we report the structures of a thermostabilized adenosine A(2A) receptor in
      complex with the xanthines xanthine amine congener and caffeine, as well as the
      A(2A) selective inverse agonist ZM241385. The receptor is crystallized in the
      inactive state conformation as defined by the presence of a salt bridge known as
      the ionic lock. The complete third intracellular loop, responsible for G protein
      coupling, is visible consisting of extended helices 5 and 6. The structures
      provide new insight into the features that define the ligand binding pocket of
      the adenosine receptor for ligands of diverse chemotypes as well as the
      cytoplasmic regions that interact with signal transduction proteins.

PMID- 21885293
TI  - Nimodipine promotes regeneration of peripheral facial nerve function after
      traumatic injury following maxillofacial surgery: an off label pilot-study.
AB  - BACKGROUND: Animal tests, retro- and prospective clinical trials in neurosurgical
      departments have shown a beneficial effect of nimodipine on the preservation and
      recovery of facial and acoustic nerve function following vestibular schwannoma
      surgery. Encouraged by these positive results a pilot-study of nimodipine
      treatment in patients with a peripheral facial nerve (FN) paresis following
      maxillofacial surgery was performed. The rate and time of FN recovery were
      analysed and compared with the results in the literature. METHODS: Thirteen
      patients (n = 13) suffering from a moderate (1/13) up to a severe (12/13)
      peripheral FN paresis after maxillofacial surgery were treated with orally
      administered nimodipine. The anatomical main course of the FN was preserved in
      all patients with a 2nd to 3rd degree of Sunderland-injury (Sunderland, 1951).
      After no evidence of a spontaneous regeneration had shown, oral medication with
      nimodipine was started as an "off-label" use. RESULTS: An improvement of the FN
      function correlated to the start of the vasoactive medication and as a
      consequence a recovery of the FN function up to House-Brackmann (HB) grade I
      degrees -II degrees  was observed in all the patients within a period of 2 months
      after the beginning of treatment (p = 0.00027). CONCLUSIONS: The clinical
      observations in these patients suggest a positive effect of nimodipine on the
      acceleration of peripheral FN regeneration after surgically caused trauma. The
      results of this pilot-study are very promising. A prospective study with a larger
      number of patients is planned to approve the beneficial effect of nimodipine on
      the peripheral FN in maxillofacial or otorhinolaryngological surgery.

PMID- 21885294
TI  - Interleukin-17F affects cartilage matrix turnover by increasing the expression of
      collagenases and stromelysin-1 and by decreasing the expression of their
      inhibitors and extracellular matrix components in chondrocytes.
AB  - Interleukin (IL)-17, a proinflammatory cytokine, is produced primarily by
      activated Th17 cells. IL-17 consists of six ligands that signal through five
      receptors (IL-17Rs); IL-17A and IL-17F share the highest homology in the family.
      Matrix metalloproteinases (MMPs) degrade the extracellular matrix during
      cartilage remodeling whereas tissue inhibitor of metalloproteinases (TIMPs)
      inhibit the action of MMPs. In the present study, we examined the effect of IL
      17F on the degradation and synthesis of the extracellular matrix in cartilage
      using human articular chondrocytes. We examined the effect of IL-17F on the
      expression of IL-17Rs, MMPs, TIMPs, type II collagen, aggrecan, link protein, and
      cyclooxygenases (COXs), as well as on prostaglandin E2 (PGE2) production. We also
      examined the indirect effect of PGE2 on the above IL-17F-induced/reduced
      components using NS-398, a specific inhibitor of COX-2. Cells were cultured with
      or without IL-17F in the presence or absence of either an IL-17R antibody or NS
      398 for up to 28 days. Expression of IL-17Rs, MMPs, TIMPs, type II collagen,
      aggrecan, link protein, and COXs at mRNA and protein levels was determined using
      real-time polymerase chain reaction and enzyme-linked immunosorbent assay
      (ELISA), respectively. PGE2 production was determined by ELISA. The expression of
      all types of IL-17Rs was detected in chondrocytes. However, IL-17RE expression
      was extremely low, compared with other IL-17Rs. The expression of MMP-1, MMP-3,
      MMP-13, and COX-2 as well as PGE2 production were increased by addition of IL
      17F, whereas the expression of IL-17RD, TIMP-2, TIMP-4, type II collagen,
      aggrecan, link protein, and COX-1 was decreased. The expression of IL-17RA, IL
      17RB, IL-17RC, MMP-2, MMP-14, TIMP-1, and TIMP-3 was unaffected by addition of IL
      17F. The IL-17R antibody blocked the stimulating/reducing effect of IL-17F on the
      expression of MMP-1, MMP-3, MMP-13, TIMP-2, TIMP-4, type II collagen, aggrecan,
      and link protein. NS-398 blocked the reducing effect of IL-17F on aggrecan
      expression, whereas it did not completely block the stimulating/reducing effects
      of IL-17F on the expression of MMP-1, MMP-3, MMP-13, TIMP-2, TIMP-4, type II
      collagen, and link protein. Our results suggest that IL-17F stimulates cartilage
      degradation by increasing the expression of collagenases (MMP-1 and -13) and
      stromelysin-1 (MMP-3) and by decreasing expression of their inhibitors (TIMP-2
      and -4), type II collagen, aggrecan, and link protein in chondrocytes.
      Furthermore, our results suggest that the expression of aggrecan, link protein,
      and TIMP-4 decrease through the autocrine action of PGE2 in chondrocytes.

PMID- 21885296
TI  - Implicit and explicit emotional behavior and mindfulness.
AB  - The objective of this study was to examine whether the "step back and watch"
      attitude of mindfulness manifests in less emotional behavior. We hypothesized
      that the "acceptance" facet of mindfulness, but not the "presence" facet, is
      negatively associated with the magnitude of emotional behavior in four tests,
      i.e., (1) rating of words, (2) rating of aversive and neutral pictures, and (3)
      evaluative conditioning (EC). Additionally, we hypothesized that (4) the
      acceptance facet is associated with increased reaction time (RT) in an emotional
      Stroop test, and that the presence facet is associated with decreased RT and
      lower error rate. The sample consisted of N=247 non-clinical adults and was
      tested in a cross-sectional study. The results provide partial evidence that the
      acceptance facet of mindfulness may be associated with less aversive reactions
      towards aversive stimuli. Future studies should substantiate these findings but
      also determine their clinical relevance.

PMID- 21885295
TI  - Venovenous extracorporeal membrane oxygenation for acute lung failure in adults.
AB  - BACKGROUND: Acute lung failure (ALF) is an increasing problem that can be treated
      with venovenous extracorporeal membrane oxygenation (vv-ECMO). This report
      summarizes prospectively collected data of an institutional experience with vv
      ECMO. METHODS: From January 2007 to December 2010, 176 patients (mean age, 48 +/-
      16; range, 14-78 years) with ALF refractory to conventional therapy were
      supported with vv-ECMO. The general indication for vv-ECMO was a partial oxygen
      pressure/fraction of inspired oxygen (Fio(2)) < 80 mm Hg under a Fio(2) of 1.0, a
      positive end-expiratory pressure of 18 cm H(2)O, and refractory respiratory
      acidosis (pH < 7.25), despite optimization of conservative therapy. RESULTS: All
      patients underwent peripheral cannulation. In 59 cases, vv-ECMO was placed in
      another facility with ECMO transport by helicopter or ambulance. The mean vv-ECMO
      support interval was 12 +/- 9.0 days (range, 1-67 days). During ECMO, 12 patients
      (7%) could be extubated and stepwise mobilized. Cannula-related complications
      during long-term support occurred in 14%, which was mostly minor bleeding.
      Overall survival was 56%: 58 patients (33%) died during mechanical support, and
      20 (11%) died after weaning from the system. The best outcome was noted in trauma
      patients. Risk factors were mainly advanced age and multiorgan failure.
      CONCLUSION: Modern vv-ECMO is an excellent treatment in patients with severe ALF
      and should be more liberally used.

PMID- 21885297
TI  - High-resolution 3-Tesla magnetic resonance neurography of musculocutaneous
      neuropathy.

PMID- 21885298
TI  - Serial structural and functional assessments of rotator cuff repairs: do they
      differ at 6 and 19 months postoperatively?
AB  - BACKGROUND: Some studies have shown that rotator cuff tendon (RCT) retears occur
      early after surgery and ultimate failure strength is reached at between 3 and 6
      months. However, few clinical studies have been reported to support their theory.
      The purpose of this study was to determine whether the RCT integrity after repair
      showed any difference at 6 months and at 19 months postoperatively. METHODS:
      Thirty-one patients who underwent complete repair for full-thickness RCT tears
      that were medium-sized tears or larger and had 2 postoperative follow-up magnetic
      resonance imaging (MRI) scans were included in this study. Retear, fatty
      degeneration, and muscle atrophy were evaluated during the first and second MRI
      sessions. Clinical assessment was performed by use of the American Shoulder and
      Elbow Surgeons score, Constant score, and pain visual analog scale preoperatively
      and at the time of the first and second MRI scans. RESULTS: The mean time for the
      two consecutive MRI scans was 5.9 months (range, 3.1-8.3 months) and 19.7 months
      (range, 10.1-24.3 months). On the first MRI scans, 24 patients had no retear, 5
      had partial retears, and 2 had full-thickness retears. In terms of rotator cuff
      retears, the 2 sets of MRI scans showed exactly the same statuses. The only
      statistically significant improvement was a reduction in tendinosis on the second
      MRI scans. In addition, significant improvements in clinical status were observed
      between the 2 periods. CONCLUSION: Our study shows that the structural status of
      RCTs after arthroscopic repair can be assessed at 6 months after surgery.
      Furthermore, although functional status improved with time after 6 months, the
      structural status of repaired cuffs remained unchanged.

PMID- 21885299
TI  - Rotator cuff tears treated with a modified deltoid flap repair technique.
AB  - BACKGROUND: Few options exist in the treatment of irreparable rotator cuff tears,
      especially in younger patients. The purpose of this study was to present our
      experience with deltoid flap repairs combined with acromion elevation osteotomy
      increasing the space for the flap. METHODS: We retrospectively reviewed the
      outcome of 57 patients with a mean age of 60 years who had undergone the modified
      anterolateral deltoid flap technique for the treatment of large and massive
      rotator cuff tears. Follow-up was performed after a mean of 6 years. RESULTS: At
      follow-up, 84% of patients considered the condition of their shoulder as better
      or much better compared with before surgery. The mean Constant score was 88%
      (range, 45-122). Before surgery, all shoulders were significantly painful. At
      latest follow-up, 91% of the patients had no or mild pain. Elevation of the arm
      above 90 degrees  was possible in 38 patients before surgery and in 53 patients
      at latest follow-up. Tears involving 3 tendons were associated with inferior
      results. Retears of the deltoid flap occurred in 8 patients (14%); 1 of them was
      successfully treated with a reverse total shoulder replacement, and 6 had a
      repair of the flap, with only 1 satisfactory outcome. CONCLUSIONS: The modified
      deltoid flap yielded reliable pain relief and a high rate of patient
      satisfaction, as well as satisfactory function in the majority of the patients.
      Especially in younger patients, this technique might be considered a viable
      alternative for the treatment of irreparable rotator cuff tears.

PMID- 21885300
TI  - Varicose veins at the spinoglenoidal notch: an unusual cause of suprascapular
      nerve compression.

PMID- 21885302
TI  - Complex fracture-dislocations of the proximal ulna and radius in adults: a
      comprehensive classification.
AB  - BACKGROUND: Complex fracture-dislocations of the proximal ulna and radius include
      multiple anatomic lesions, the management of which is known to be demanding.
      Although several classifications have been proposed, none appear to be
      exhaustive, and most of them have neither therapeutic nor prognostic value. The
      purpose of this study was to design a comprehensive classification that may
      provide a guide for the operative management of these injuries. MATERIALS AND
      METHODS: The classification is aimed at identifying definite anatomic lesions,
      called the "main lesions," the presence of which can affect the prognosis and
      require peculiar treatments. The main lesions include (1) ulnar fracture
      (including its location with respect to the insertion of collateral ligaments and
      coronoid fracture), (2) radiohumeral dislocation, (3) proximal radioulnar
      dislocation, (4) radial fracture, (5) distal radioulnar joint and interosseous
      membrane lesion, and (6) humeral-ulnar dislocation. Intraobserver and
      interobserver reliability was assessed in 25 complex fracture-dislocations.
      Standard radiographs and computed tomography scans were analyzed by 3 independent
      observers. RESULTS: The main lesions were labeled by an alphanumeric system.
      Numbers 1 through 6 identified the type of ulnar fracture, and letters A through
      E indicated the dislocated joint or presence of a radial fracture. The direction
      of dislocation and the type of radial fracture were identified by Roman numerals,
      from I to III, placed after the letter. A kappa value of 0.873 or greater
      resulted from intraobserver and interobserver evaluation. CONCLUSION: We created
      a comprehensive classification of complex fracture-dislocations of the elbow. The
      classification appeared to be reproducible and may represent a useful tool for
      the management of such difficult injuries.

PMID- 21885301
TI  - The biomechanical role of scaffolds in augmented rotator cuff tendon repairs.
AB  - BACKGROUND: Scaffolds continue to be developed and used for rotator cuff repair
      augmentation; however, the appropriate scaffold material properties and/or
      surgical application techniques for achieving optimal biomechanical performance
      remains unknown. The objectives of the study were to simulate a previously
      validated spring-network model for clinically relevant scenarios to predict: (1)
      the manner in which changes to components of the repair influence the
      biomechanical performance of the repair and (2) the percent load carried by the
      scaffold augmentation component. MATERIALS AND METHODS: The models were
      parametrically varied to simulate clinically relevant scenarios, namely, changes
      in tendon quality, altered surgical technique(s), and different scaffold designs.
      The biomechanical performance of the repair constructs and the percent load
      carried by the scaffold component were evaluated for each of the simulated
      scenarios. RESULTS: The model predicts that the biomechanical performance of a
      rotator cuff repair can be modestly increased by augmenting the repair with a
      scaffold that has tendon-like properties. However, engineering a scaffold with
      supraphysiologic stiffness may not translate into yet stiffer or stronger
      repairs. Importantly, the mechanical properties of a repair construct appear to
      be most influenced by the properties of the tendon-to-bone repair. The model
      suggests that in the clinical setting of a weak tendon-to-bone repair, scaffold
      augmentation may significantly off-load the repair and largely mitigate the poor
      construct properties. CONCLUSIONS: The model suggests that future efforts in the
      field of rotator cuff repair augmentation may be directed toward strategies that
      strengthen the tendon-to-bone repair and/or toward engineering scaffolds with
      tendon-like mechanical properties.

PMID- 21885303
TI  - An anatomic study of coronoid cartilage thickness with special reference to
      fractures.
AB  - BACKGROUND: Current coronoid fracture classification systems are based on
      fragment size and configuration using plain radiographs and/or computed
      tomography (CT). During surgery, coronoid fracture fragments appear much larger
      than anticipated because cartilage is radiolucent and therefore not accounted for
      with preoperative imaging. The purpose of this imaging study was to quantify the
      articular cartilage thickness of the coronoid, with reference to coronoid
      fractures. MATERIALS AND METHODS: Twenty-four cadaveric ulnae were dissected,
      imaged with CT, and analyzed by use of image analysis software. Thirteen
      identifiable landmarks were chosen on the coronoid, olecranon, and proximal
      radioulnar joint to measure articular cartilage thickness. Intraobserver
      reliability and interobserver reliability were determined. RESULTS: Cartilage
      thickness was highest at the coronoid tip, with a mean of 3.0 mm (range, 1.7-4.6
      mm). Cartilage thickness at the tip correlated inversely with age (P < .01) and
      correlated strongly with overall ulnar height and ulnar length (P < .05). All
      measurements had excellent intraobserver and interobserver reliability.
      CONCLUSION: The thickness of cartilage on the coronoid tip is not
      inconsequential. The results of this study indicate that a 2-mm coronoid tip
      fracture on CT scan may actually appear to be a mean of 5 mm thick when viewed at
      the time of surgery. Clinically, this is important because it may alter the
      classification, the decision to treat, or the type of fixation used. Importantly,
      biomechanical cadaveric studies assessing coronoid injuries have incorporated
      cartilage thickness into coronoid size measurements when creating simulated
      fractures; therefore, it is critical that the conclusions of such biomechanical
      studies be scrutinized with regard to their clinical recommendations. Surgeons
      should be aware of these discrepancies.

PMID- 21885304
TI  - Metformin in equine metabolic syndrome: an enigma or a dead duck?

PMID- 21885305
TI  - Introductory comment: Childhood tight filum syndrome.

PMID- 21885306
TI  - Second order gradient ascent pulse engineering.
AB  - We report some improvements to the gradient ascent pulse engineering (GRAPE)
      algorithm for optimal control of spin ensembles and other quantum systems. These
      include more accurate gradients, convergence acceleration using the Broyden
      Fletcher-Goldfarb-Shanno (BFGS) quasi-Newton algorithm as well as faster control
      derivative calculation algorithms. In all test systems, the wall clock time and
      the convergence rates show a considerable improvement over the approximate
      gradient ascent.

PMID- 21885307
TI  - Triple resonance three-dimensional protein NMR: before it became a black box.
AB  - Three-dimensional triple resonance experiments have become an integral part of
      virtually every solution NMR study of proteins. The approach relies on uniform
      isotopic enrichment of proteins with (13)C and (15)N, and establishes the scalar
      connectivity pathway between nuclei through the large (1)J(NH), (1)J(CH)(,
      1)J(CC), and (1)J(CN) couplings. The magnetization transfer process takes place
      through multiple, efficient one-bond magnetization transfer steps, rather than a
      single step through the smaller and variable (3)J(HH) couplings. The relatively
      large size and good uniformity of the one-bond couplings allowed the design of
      efficient magnetization transfer schemes that are effectively uniform across a
      given protein, nearly independent of conformation. Although conceptually
      straightforward, practical implementation of three-dimensional triple resonance
      experiments on proteins originally posed serious challenges. This account
      provides a personal perspective on some of the historical background to this
      work, the problems encountered as well as their solutions, and their evolution
      into today's standard arsenal of experiments.

PMID- 21885308
TI  - Reduction of magnetic field fluctuations in powered magnets for NMR using
      inductive measurements and sampled-data feedback control.
AB  - Resistive and hybrid (resistive/superconducting) magnets provide substantially
      higher magnetic fields than those available in low-temperature superconducting
      magnets, but their relatively low spatial homogeneity and temporal field
      fluctuations are unacceptable for high resolution NMR. While several techniques
      for reducing temporal fluctuations have demonstrated varying degrees of success,
      this paper restricts attention to methods that utilize inductive measurements and
      feedback control to actively cancel the temporal fluctuations. In comparison to
      earlier studies using analog proportional control, this paper shows that shaping
      the controller frequency response results in significantly higher reductions in
      temporal fluctuations. Measurements of temporal fluctuation spectra and the
      frequency response of the instrumentation that cancels the temporal fluctuations
      guide the controller design. In particular, we describe a sampled-data phase-lead
      lag controller that utilizes the internal model principle to selectively
      attenuate magnetic field fluctuations caused by the power supply ripple. We
      present a quantitative comparison of the attenuation in temporal fluctuations
      afforded by the new design and a proportional control design. Metrics for
      comparison include measurements of the temporal fluctuations using Faraday
      induction and observations of the effect that the fluctuations have on nuclear
      resonance measurements.

PMID- 21885309
TI  - NMR studies of protein structure and dynamics - a look backwards and forwards.
AB  - NMR spectroscopy has evolved to become one of the most powerful tools for the
      study of protein structure and dynamics. Advances over the past decade have
      greatly extended the methodology to studies of molecules of ever increasing
      complexity. Herein I provide a short perspective relating the circumstances that
      led to some of the contributions from my laboratory in this area and highlight
      how these original experiments, summarized in a Journal of Magnetic Resonance
      article in 2005 (JMR, 173 193-207), have influenced the current focus of my
      research.

PMID- 21885310
TI  - Evaluation of medetomidine, ketamine and buprenorphine for neutering feral cats.
AB  - A combination of medetomidine (M, 100 MUg/kg), ketamine (K, 10 mg/kg) and
      buprenorphine (B, 10 MUg/kg), administered by intramuscular injection, was
      evaluated for spaying and castration (neutering) of feral cats (n = 101). Eleven
      animals (11%) required supplemental anesthesia (isoflurane by mask) to maintain
      an adequate plane of surgical anesthesia. Atipamezole (A, 125 MUg/kg) was
      administered subcutaneously at the completion of surgery. All cats recovered from
      surgery and were released the following day. A hemoglobin saturation (SpO(2))
      value of < 95% was recorded at least once during anesthesia in all cats. This MKB
      combination can be used in a feral cat sterilization clinic, but isoflurane
      supplementation may be necessary. Further research is indicated to determine the
      clinical significance of the low SpO(2) values associated with this anesthetic
      regimen.

PMID- 21885311
TI  - Detection of protective antibody titers against feline panleukopenia virus,
      feline herpesvirus-1, and feline calicivirus in shelter cats using a point-of
      care ELISA.
AB  - Serum antibody titers are a useful measurement of protection against infection
      (feline panleukopenia virus [FPV]) or clinical disease (feline herpesvirus-1
      [FHV] and feline calicivirus [FCV]), and their determination has been recommended
      as part of disease outbreak management in animal shelters. The objective of this
      study was to determine the sensitivity, specificity, and inter-observer and inter
      assay agreement of two semi-quantitative point-of-care assays for the detection
      of protective antibody titers (PAT) against FPV, FHV and FCV in shelter cats. Low
      sensitivity for FPV antibodies (28%) rendered a canine point-of-care assay
      inappropriate for use in cats. The feline point-of-care assay also had low
      sensitivity (49%) and low negative predictive value (74%) for FPV PAT detection,
      but was highly accurate in the assessment of FHV and FCV PAT. Improvements in
      accuracy and repeatability of FPV PAT determination could make this tool a
      valuable component of a disease outbreak response in animal shelters.

PMID- 21885312
TI  - Biliothorax in a Siamese cat.
AB  - A 2-year-old male neutered cat presented for further investigation of
      biliothorax. The cat was initially treated for pyothorax, including bilateral
      chest drains for lavage of the pleural space. Five days later, the pleural
      effusion turned clear-yellow and had a bilirubin concentration of 427 MUmol/l
      compared to the serum bilirubin concentration of 15 MUmol/l. Exploratory surgery
      revealed a 2mm tear in the diaphragm, with a corresponding 2mm defect in the
      diaphragmatic surface of the gall bladder, creating a fistula between the gall
      bladder and the pleural cavity. The defects were repaired routinely and the cat
      made a full recovery. It was suspected that the tears had been created at the
      time of the thoracostomy tube placement. Biliothorax has not been described
      before in a cat, and appears to be a rare complication following thoracostomy
      tube placement.

PMID- 21885313
TI  - [Reliability of the Nursing Outcome "Knowledge: Health Resources" when used in
      primary and hospital care].
AB  - AIMS: To study the reliability (inter-observer agreement and internal
      consistency) of the Spanish version of the Nursing Outcome "Knowledge: Health
      Resources" and determine the differences in reliability when used by nurses in
      two settings: community care and hospital care. METHOD: Reliability study. 12
      experienced nurses were paired (community and hospital) to use this nursing
      outcome questionnaire to assess health service users. Data were obtained by
      direct interview with 60 patients. Statistical analysis was performed to obtain;
      weighted kappa index, Intraclass Correlation Coefficient (ICC), and internal
      consistency by Cronbach's alpha. RESULTS: The inter-observer agreement on the
      "Knowledge: Health Resources" outcome in Spanish was measured by weighted Kappa
      0.557 (95% CI=0.381-0.733) and Intraclass Correlation Coefficient of 0.561 (95%
      CI=0.361-0.712). The indicators showed values ranging from kappa=0.268 I to
      kappa=0.507. The internal consistency was high (Cronbach's alpha=0.854). There
      were no statistically significant differences in reliability when used in
      different settings: community care and hospital. CONCLUSIONS: The Spanish version
      of this nursing outcome has a moderate reliability. A cultural adaptation of this
      outcome should be made.

PMID- 21885315
TI  - [Impact of the use of CPAP on the quality of life of patients with obstructive
      sleep apnea].

PMID- 21885314
TI  - [Randomised controlled clinical trial to determine the effects of the use of
      birth balls during labour].
AB  - OBJECTIVE: To determine the effects of using birth balls (BB) during the first
      and second stage of labour, perineal integrity, perception of pain intensity, and
      safety. METHOD: Randomised controlled trial. PARTICIPANTS: 18 to 35 years,
      nulliparous, low-risk, at term. INTERVENTION: Performing movements sitting on a
      BB during obstetric labour. MAIN OUTCOMES: Duration of first and second labour
      stages; perineal integrity; pain perception during the postpartum period and pre
      post intervention, type of delivery, cause of dystocia, Apgar, neonatal ICU
      admission. ANALYSIS: Comparison of groups: Student-t for continuous variables and
      chi-squared test for categorical ones. Significance if P <=.05. RESULTS: A total
      of 58 patients (34 experimental and 24 controls) were included. Times of first
      and second stage, and perineal integrity were similar between groups. At 4 cm.
      the experimental group referred less pain than the control group, 6.9 points vs
      8.2 (P=.039). Difference in the perception of pain in the immediate postpartum
      period was 1.48 points higher in the control group (P=.003). The measurement of
      pain in the experimental group before the use of the BB was of 7.45 points, and
      after the intervention of 6.07 points (P<.001). In There were no differences
      between groups as regards safety-related variables. CONCLUSION: The use of a
      Birth Ball decreases obstetric labour pain perception and is safe.

PMID- 21885316
TI  - CD4+ cell counts and HIV-RNA levels do not predict outcomes of community-acquired
      pneumonia in hospitalized HIV-infected patients.
AB  - BACKGROUND: Outcomes of community-acquired pneumonia (CAP) in relation to CD4+
      cell counts have not been established. We examined the correlation of CD4+ cell
      count and HIV-RNA level with the clinical outcomes of CAP in hospitalized HIV
      infected patients. METHODS: This was a retrospective study of 127 adult
      hospitalized patients with HIV infection enrolled with the CAP Organization
      (CAPO), examining the time to clinical stability (TCS), length of hospital stay
      (LOS), and all-cause mortality. RESULTS: Mortality data were available for 117
      HIV-infected patients with CAP. Death within 28 days was reported in 28 patients.
      The risk of mortality at 28 days was not significant when adjusted for CD4+ cell
      count (p=0.123), HIV-RNA <400-1000 copies/ml (p=0.093), HIV-RNA >= 1000-10,000
      copies/ml (p=0.543), and HIV-RNA >= 10,000-100,000 copies/ml (p=0.383). The
      propensity-adjusted Cox proportional hazards regression models did not show any
      statistically significant differences in LOS or TCS for CD4+ cell counts (p=0.590
      and p=0.420, respectively) or HIV-RNA levels (p=0.470 and p=0.080, respectively).
      Multivariable Cox proportional hazards models did not reveal any statistically
      significant relationships between CD4+ cell counts or HIV-RNA levels with LOS or
      TCS. CONCLUSIONS: Our study shows that clinical outcomes of HIV-infected patients
      with CAP are not predicted by CD4+ cell counts or HIV-RNA levels after adjusting
      for confounders. The management of CAP in patients with HIV infection should not
      be based on CD4+ cell counts or HIV-RNA levels of the HIV infection.

PMID- 21885317
TI  - [Induction chemotherapy for head and neck epidermoid carcinomas].
AB  - The standard treatment for head and neck inoperable squamous cell carcinoma is an
      association of radiotherapy and platinum. However, only one patient out of three
      remains alive five years after diagnosis. The interest in induction chemotherapy
      was renewed by the introduction of taxanes combined with cisplatinum and 5-fluoro
      uracile. The triple association taxane-cisplatinum-5-fluoro-uracile yielded
      improved survival when compared to cisplatinum-5-fluoro-uracile. Wider use of
      taxane-cisplatinum-5-fluoro-uracile is limited by its toxicity and the lack of
      randomized comparison with a concomitant chemoradiotherapy scheme including
      optimal doses of platinum. Until the results of new phase III trials are
      published, the choice between induction chemotherapy followed by concomitant
      chemoradiotherapy or concomitant chemoradiotherapy alone has to be made on an
      individualized basis, taking into account the patient's medical condition, the
      ability of the medical team to deal with intensive treatment regimens, and the
      clinical/pathological characteristics of the tumour.

PMID- 21885318
TI  - [Targeted therapies and radiation therapy in non-small cell lung cancer].
AB  - Lung cancer is the leading cause of cancer-related death. Between 80-85% of lung
      cancers are non-small cell lung carcinomas. One third of the patients are
      diagnosed with locally advanced stage. In this condition, concomitant radio
      chemotherapy is the standard treatment for patients with good performance status.
      Despite important improvements in the last years, non-small cell lung carcinoma
      prognosis remains poor, with high rates of both local recurrences and metastases.
      The heterogeneity of molecular characteristics of non-small cell lung carcinoma
      cells and a better knowledge of potential targets offer promising developments
      for new pharmacologic agents. Hereafter we will review the currently most studied
      pathways and the most promising ones for the treatment of locally advanced
      unresectable non-small cell lung carcinoma. Two of the most attractive pathways
      where new agents have been developed and assessed in combination with thoracic
      radiotherapy or radiochemotherapy are the EGFR pathway (either with the use of
      monoclonal antibodies or tyrosine kinase inhibitors) and the angiogenesis
      inhibition. The development of targeted agents could lead to individualized
      therapeutic combinations taking into account the intrinsic characteristics of
      tumor cells. Pharmacological modulation of tumour cells radiosensitivity by
      targeted therapies is only starting, but yet offers promising perspectives.

PMID- 21885319
TI  - [Chemotherapy and rectal cancer].
AB  - Chemotherapy does not increase the survival time of patients treated for rectal
      cancer. Chemotherapy given concomitantly to radiotherapy and combined before or
      after radiation significantly reduces the risk of local recurrence. The
      sterilization of the tumour (complete pathological response) by chemotherapy is a
      favourable prognostic factor. New trials on optimisation of pathological complete
      response rates are based on using drugs effective on metastatic colorectal
      cancer, given prior to chemoradiotherapy and followed by a resection at least 8
      weeks after the end of the radiotherapy. The level of evidence for postoperative
      chemotherapy is low due to lack of specific study. The indication of
      postoperative chemotherapy depends on the disease extent after preoperative
      treatment.

PMID- 21885320
TI  - [Radiation-related heart toxicity].
AB  - The radiotherapy of thoracic cancers exposes the heart to late radiation-induced
      complications. The physiopathological and clinical consequences of heart
      irradiation have been mostly studied in patients with Hodgkin lymphoma and breast
      cancer. The main cause of cardiac morbidity is radiation-induced coronaropathy
      with a relative risk estimated between 2 and 3 in earlier studies. Preexisting
      factors of cardiovascular risk, including chemotherapy, potentalize the
      cardiotoxicity of radiotherapy. Conformational radiotherapy, adapting the
      ballistics and the energy to the delineated volumes while carefully evaluating
      the dose-volume distribution in the organs at risk, allowed a drastic reduction
      in cardiac mortality. This toxicity no longer seems to be significant if the
      cardiac volume has received less than 30 Gy. Nevertheless, the prolonged life
      expectancy of cancer patients and the expanding use of new cardiotoxic anticancer
      drugs underline the persistent need to further reduce the dose delivered to the
      heart. Indeed, 1 Gy added to the mean heart dose would increase the cardiotoxic
      risk by 4% (IC 95%: 2-6%, P=0.0002). A strengthened collaboration between the
      radiation oncologist and the cardiologist aims at detecting and treating long
      term complications after thoracic radiotherapy.

PMID- 21885321
TI  - [Intensity modulated radiotherapy for intrathoracic cancers: a dangerous liaison?
      Our experience in the treatment of Hodgkin lymphoma mediastinal masses].
AB  - IMRT is a seducing treatment option in patients with Hodgkin lymphoma mediastinal
      masses due to the complex form of the tumour masses and their proximity to organs
      at risk such as the heart and the coronary arteries. This treatment delivery
      technique remains risky owing to respiratory movements and heart beats. The
      concomitant use of IMRT and respiratory gating is enticing, but a number of
      theoretical and practical hurdles remain to be resolved before it can be used in
      clinical daily practice.

PMID- 21885322
TI  - Cardiac 123I-meta-iodobenzylguanidine scintigraphy in patients with amyotrophic
      lateral sclerosis and parkinsonism-dementia complex of the Kii peninsula, Japan.

PMID- 21885323
TI  - Selective internal migration. Does it explain Glasgow's worsening mortality
      record?
AB  - The mortality difference between Glasgow and the rest of Scotland has been
      increasing and mortality rates are higher than Glasgow's excess deprivation would
      suggest. One plausible explanation for this excess is selective migration. A
      sample of 137,073 individuals aged 15 to 64 in 1991 from the Scottish
      Longitudinal Study was used to test this explanation. Three geographic areas were
      compared: Glasgow; Aberdeen, Dundee and Edinburgh cities combined and the rest of
      Scotland. The impact of selective migration was assessed by calculating age and
      sex standardised mortality rates for 2001/03 by residence in 2001 and by
      residence in 1991. Glasgow experienced the greatest loss of population (-7.1%)
      between 1991 and 2001 but this was not strongly related to deprivation. It had
      the highest mortality at baseline and the difference between it and the other
      areas increased over the ten years. This pattern was not significantly affected
      by calculating death rates according to area of residence at 1991 or in 2001. Our
      results suggest that the increasing difference in mortality rates between Glasgow
      and the rest of Scotland over this period was probably not caused by selective
      migration.

PMID- 21885324
TI  - Income disparities in perceived neighborhood built and social environment
      attributes.
AB  - The present study explored whether perceived neighborhood environmental
      attributes associated with physical activity differ by neighborhood income.
      Adults aged 20-65 years (n=2199; 48% female; mean age=45 years; 26% ethnic
      minority) were recruited from 32 neighborhoods from the Seattle, WA and
      Baltimore, MD regions that varied in objectively measured walkability and
      neighborhood income. Perceived built and social environment variables were
      assessed with the Neighborhood Environment Walkability Scale. There were
      neighborhood income disparities on 10 of 15 variables. Residents from high-income
      neighborhoods reported more favorable esthetics, pedestrian/biking facilities,
      safety from traffic, safety from crime, and access to recreation facilities than
      residents of low-income areas (all p's <0.001). Low-income neighborhoods may lack
      amenities and safety attributes that can facilitate high levels of physical
      activity for both transportation and recreation purposes.

PMID- 21885325
TI  - Non-contact meibography: keep it simple but effective.
AB  - PURPOSE: Meibography is reported to be important in Meibomian Gland Dysfunction
      (MGD) evaluation. Our purpose was to investigate the usefulness of a standard
      infra-red video security camera in meibography. METHODS: Meibographs were taken
      of the right lower lid of 17 subjects (female 10; age = 44.3 years +/-13.3 SD),
      randomly selected from the patient pool of Horst Riede GmbH, Weinheim, Germany.
      Meibomian glands (MG) were photographed by an near adapted infra-red video
      security camera and extend of MG loss (MGL) was measured by digital image
      analyzes. Lipid-layer and non-invasive break-up time (NIBUT) was measured by
      tearscope, dry eye symptoms were evaluated by the Ocular Surface Disease Index
      (OSDI). Correlations between MGL scores and ocular signs, tearfilm and symptoms
      were analyzed by Pearsons, differences between gender by U-test. The ability of
      MGL to predict dry eye symptoms was evaluated by area under the receiver
      operative characteristic curve (AUC). RESULTS: MGL scores were significantly
      correlated to lipid-layer pattern (r = -0.68, p = 0.001) NIBUT (-0.46, 0.032)
      OSDI (0.89, 0.001) and age (0.61, 0.005). MGL was significantly larger in female
      (p = 0.001). AUC of MGL was 95.8% (p = 0.001; sensitivity = 88.9%; specificity =
      87.5%; threshold = 32.3%). CONCLUSIONS: MGL is a predictive test of dry eye
      symptoms. The analyzed significant correlation between MGL and tearfilm and dry
      eye symptoms indicates the usefulness of the non-contact IR meibograph (PNCM).

PMID- 21885326
TI  - Correlation of central and peripheral corneal thickness in healthy corneas.
AB  - PURPOSE: To study the thickness profile of the normal cornea in order to
      establish any correlation between central and peripheral points. METHODS: Sixty
      seven eyes of 40 patients were subjected to central corneal thickness measurement
      (CCT) with an ultrasound pachymeter (UP) and corneal thickness mapping with the
      Oculus Pentacam. The corneal apex thickness (CAT), pupil centre thickness
      (recorded as CCT and corresponded to CCT of UP) and thickness at the thinnest
      location (CTL) were obtained and compared with each other. Corneal thickness data
      at 3 mm and 7 mm temporally, nasally, superiorly and inferiorly from the corneal
      apex were obtained. The mean corneal thickness values along the 2, 4, 6, 8 and 10
      mm diameter concentric circles, with the CTL as the centre, were also obtained.
      The above data at different points were statistically correlated. RESULTS: There
      was no significant difference between CCT readings measured by UP and Pentacam
      (P=0.721). There was high positive correlation between the CAT values and the
      thickness at 3 mm (R>=0.845, P<0.001) and at 7 mm points (R>=0.654, P<0.001). A
      gradual increase in thickness was noted from the centre to the periphery with a
      high positive correlation between the CTL values and the mean thickness at the
      circles of 2, 4, 6, 8 and 10 mm (R>=0.635, P<0.001). CONCLUSION: The results
      suggest that central corneal thickness can serve as a good guide for predicting
      peripheral thickness. For surgical procedures specifically undertaken at mid
      peripheral and peripheral zones, the actual measurements at the site of surgery
      may confer some advantage.

PMID- 21885327
TI  - A rare case of penetrating ocular injury secondary to a boa constrictor bite.
AB  - Penetrating injuries from non-venomous snakebites are, thankfully, rare. They
      are, however, sight-threatening and the recent trend for using non-venomous
      snakes as props in the entertainment industry is increasing exposure of this
      hazard to people with no animal handling training. We report a case of a
      penetrating corneal injury in a 35 year old woman following a bite from a snake
      she had been given to hold for a photograph opportunity. The injury was repaired
      surgically and she had a good visual outcome, largely due to very good fortune in
      the site and nature of the injury. This case highlights the danger of exposing
      untrained handlers to snakes in the entertainment industry.

PMID- 21885328
TI  - Co-morbidity and treatment outcomes of elderly pharyngeal cancer patients: a
      matched control study.
AB  - Treatment choice in elderly pharyngeal cancer patient is disputed. This study was
      aimed to asses association of co-morbidity, complications and survival in
      different treatment modalities of pharyngeal cancer patients. Retrospective
      analysis of pharyngeal cancer patients, diagnosed between 1997 and 2007 in a
      tertiary referral hospital was performed. Patients 75years and older (n=42), were
      matched with two control patients 64years and younger (n=84). Co-morbidity (ACE
      27), treatment related complications and survival data were assessed and
      analyzed. Frequency of co-morbidity was similar in both age groups, although
      discarding alcohol abuse resulted in higher incidence of co-morbidity in the
      elderly group. Complication rate was not significantly different. In a
      multivariate analysis only stage found to be a significant predictor of
      complications. Survival estimates adjusted to sex, age and birth cohort revealed
      co-morbidity to be a significant predictor for survival in elderly and young
      patients. No evidence has been found to treat elderly pharyngeal cancer patients
      differently than younger ones. Treatment related complications are not predicted
      by co-morbidities in young and elderly patients; however survival is predicted by
      comorbidity. Therefore thorough pre-treatment evaluation and care necessary in
      the elderly population.

PMID- 21885329
TI  - Parvovirus B19-associated purpuric-petechial eruption.
AB  - BACKGROUND: Papular-purpuric gloves-and-socks syndrome, characterized by focal
      acral purpuric eruptions with a symmetrical distribution, is a rare but
      representative purpuric dermatosis closely associated with parvovirus B19 (PVB19)
      infection. However, several atypical presentations such as involvement of other
      sites and generalized involvement have been recently reported in PVB19 infected
      patients. Such multifaceted features can cause considerable confusion when making
      a diagnosis of purpuric eruption associated with PVB19. OBJECTIVES: Describe two
      febrile patients with atypical presentation of papular-purpuric eruptions due to
      PVB19 infection and discuss the distinctive features of purpuric-petechial
      eruptions associated with PVB19 infection. STUDY DESIGN: Case reports and viral
      diagnosis by serologic tests and real-time PCR for PVB19 DNA in the serum.
      RESULTS: One presented with "asymmetrical gloves without socks" distribution of
      papular purpuric eruptions accompanied by asymmetrical intertriginous
      involvement, the other with generalized distribution characterized by prominent
      intertriginous and truncal involvement. Both cases were followed by erythema
      infectiosum. Paired serum antibody analysis and real-time PCR indicated the link
      between the development of papular purpuric eruption and the viremic phase of
      primary PVB19 infection. CONCLUSIONS: PVB19 infection should be considered in any
      patient presenting with a petechial or purpuric eruption of unclear origin, and
      not solely for PPGSS type presentations. Therefore, we propose a simple name
      "PVB19-associated purpuric-petechial eruption" to describe polymorphous purpuric
      petechial eruptions due to PVB19 infection, coinciding with the viremic phase of
      primary infection and infectivity, characterized by a self-limiting course with a
      benign prognosis and common histological findings.

PMID- 21885330
TI  - Molecular characterization and tissue distribution of ferritin M in kelp grouper,
      Epinephelus bruneus.
AB  - This study, reports the identification and analysis of ferritin M chain, from
      kelp grouper, Epinephelus bruneus (EbFerM); it comprises 1004 base pair (bp),
      including 528bp open reading frame (ORF) which encodes 176 amino acid (aa)
      residues; the calculated molecular weight is 20kDa. The 5'-untranslated region
      (UTR) possesses 476bp proceeded by a putative Iron Regulatory Element (IRE). Pair
      wise alignments showed that EbFerM shared 94% identity with that of Larimichthys
      crocea and Sciaenops. It is expressed in abundance in liver, spleen, and kidney
      when challenged with Vibrio anguillarum, lipopolysaccharide (LPS), or poly I:C.

PMID- 21885331
TI  - Narcolepsy and traumatic brain injury: cause or consequence?

PMID- 21885332
TI  - What's next after the exciting discovery and reassuring replications of genome
      wide association studies of restless legs syndrome?

PMID- 21885333
TI  - Health effects of disinfection by-products in chlorinated swimming pools.
AB  - Increased attendance at swimming pools is correlated with higher input of organic
      and minerals pollutants introduced by swimmers in the swimming pool water. In
      most swimming pools, microbiological control is performed by disinfection with
      the addition of chlorine. Chlorine is now well-known to lead to the formation of
      many disinfection by-products (DBPs) including trihalomethanes and chloramines.
      The hypothesis of a link between the presence of eye and skin irritation
      syndromes in swimmers and contact with swimming pool water treated with chlorine
      was initially proposed by Mood (1953). During recent decades many epidemiological
      studies have described the importance of DBPs generated with natural or imported
      organic matter present in water. Many of these DBPs are suspected to be toxic or
      even carcinogenic. Trihalomethanes and haloacetic acid families are the most
      studied but others DBPs, like chloral hydrate, haloacetonitriles, N
      nitrosodimethylamine and the bromate ion, are emerging compounds of interest.
      Epidemiological data about the risk of cancer are still controversial. However,
      numerous publications highlight a toxic risk especially the risk of allergy and
      respiratory symptoms for babies and elite swimmers. The few publications
      dedicated to risk assessment do not suggest increased risk, other than for elite
      swimmers. These publications are likely to underestimate the risk associated with
      DBPs because of the lack of data in the literature precludes the calculation of
      risk associated with certain compounds or certain pathways. Thus for regulations,
      the need to take into account the risks associated with disinfection by-products
      is now important without forgetting the need of the control of microbiological
      hazards in swimming pools.

PMID- 21885334
TI  - Drug residues and endocrine disruptors in drinking water: risk for humans?
AB  - The presence of pharmaceuticals and endocrine disruptors in the environment
      raises many questions about risk to the environment and human health.
      Environmental exposure has been largely studied, providing to date a realistic
      picture of the degree of contamination of the environment by pharmaceuticals and
      hormones. Conversely, little information is available regarding human exposure.
      NSAIDS, carbamazepine, iodinated contrast media, beta-blockers, antibiotics have
      been detected in drinking water, mostly in the range of ng/L. it is questioned if
      such concentrations may affect human health. Currently, no consensus among the
      scientific community exists on what risk, if any, pharmaceuticals and endocrine
      disruptors pose to human health. Future European research will focus, on one
      hand, on genotoxic and cytotoxic anti-cancer drugs and, on the other hand, on the
      induction of genetic resistance by antibiotics. This review does not aim to give
      a comprehensive overview of human health risk of drug residues and endocrine
      disruptors in drinking water but rather highlight important topics of discussion.

PMID- 21885335
TI  - Emerging pollutants in wastewater: a review of the literature.
AB  - For 20 years, many articles report the presence of new compounds, called
      "emerging compounds", in wastewater and aquatic environments. The US EPA (United
      States - Environmental Protection Agency) defines emerging pollutants as new
      chemicals without regulatory status and which impact on environment and human
      health are poorly understood. The objective of this work was to identify data on
      emerging pollutants concentrations in wastewater, in influent and effluent from
      wastewater treatment plants (WWTPs) and to determine the performance of sewage
      disposal. We collected 44 publications in our database. We sought especially for
      data on phthalates, Bisphenol A and pharmaceuticals (including drugs for human
      health and disinfectants). We gathered concentration data and chose 50
      pharmaceutical molecules, six phthalates and Bisphenol A. The concentrations
      measured in the influent ranged from 0.007 to 56.63 MUg per liter and the removal
      rates ranges from 0% (contrast media) to 97% (psychostimulant). Caffeine is the
      molecule whose concentration in influent was highest among the molecules
      investigated (in means 56.63 MUg per liter) with a removal rate around 97%,
      leading to a concentration in the effluent that did not exceed 1.77 MUg per
      liter. The concentrations of ofloxacin were the lowest and varied between 0.007
      and 2.275 MUg per liter in the influent treatment plant and 0.007 and 0.816 MUg
      per liter in the effluent. Among phthalates, DEHP is the most widely used, and
      quantified by the authors in wastewater, and the rate of removal of phthalates is
      greater than 90% for most of the studied compounds. The removal rate for
      antibiotics is about 50% and 71% for Bisphenol A. Analgesics, anti inflammatories
      and beta-blockers are the most resistant to treatment (30-40% of removal rate).
      Some pharmaceutical molecules for which we have not collected many data and which
      concentrations seem high as Tetracycline, Codeine and contrast products deserve
      further research.

PMID- 21885336
TI  - Impact of Warden's procedure on the sinus rhythm: our experience.
AB  - OBJECTIVES: Our experience with the use of Warden's procedure for the repair of
      sinus venosus ASD with anomalous right upper pulmonary venous connection. METHOD:
      Fifty-eight patients had Warden's procedure from September 2008 to May 2011. The
      demographic data, preoperative and postoperative ECG, aortic cross-clamp time,
      cardiopulmonary bypass time, Holter monitoring, complications length of ICU and
      hospital stay were analysed. RESULT: The male to female ratio was 1:1. The median
      age was 10.9 years (range 2-48 years). Preoperatively all patients were in sinus
      rhythm. Twenty-six patients had associated left superior vena cava and two
      patients had also Tucker's procedure at the same time. The mean follow up was 1.2
      years (range 1 months-2.8 years). Postoperative Holter monitoring showed sinus
      rhythm in all the patients. The mean CPB time was 83.6 min (range 54-163 min),
      mean aortic cross-clamp time was 48.0 min (range 22-112 min), mean ICU stay was
      1.26 days (range 1-4 days) and length of hospital was 8.3 days (range 5-13 days)
      Postoperative echocardiography showed less than 1 mm Hg gradient across the SVC
      RA appendage anastomotic site in all the patients. No mortality was recorded.
      CONCLUSION: This is the largest reported series of Warden's procedure in the
      literature till date. It is known from other studies that sinus node dysfunction
      and conversion to junctional nodal rhythm were quite a concern with the
      conventional techniques and Warden's procedure specifically avoids these
      problems.

PMID- 21885337
TI  - Stroke, aortic vegetations and disseminated adenocarcinoma--a case of marantic
      endocarditis.
AB  - Herein we describe a case of marantic endocarditis (non-bacterial thrombotic
      endocarditis) that presented with coronary, cerebral and peripheral emboli,
      fevers and malaise, and negative blood cultures. The 'kissing lesions' on all
      three leaflets of the aortic valve were bulky and friable. After aortic valve
      surgery, an acute abdomen prompted laparoscopy which demonstrated disseminated
      adenocarcinoma. We discuss the clinical presentation of this rare condition and
      the importance of considering marantic endocarditis secondary to malignancy as a
      differential diagnosis for culture negative endocarditis.

PMID- 21885338
TI  - Guidelines for the diagnosis and management of arrhythmogenic right ventricular
      cardiomyopathy.
AB  - BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an uncommon
      inherited myocardial disorder characterised by fibro-fatty inflammation affecting
      the right and left ventricles. It most commonly presents with palpitations or
      syncope but sudden death may occur, especially in young males. METHODS: Diagnosis
      is not possible with a single test and may be difficult. Task Force criteria
      agreed in 1994 comprise major and minor criteria spanning structural
      abnormalities, ECG appearances, arrhythmias, family history of premature death
      and myocardial histology. Modified criteria were introduced in 2010 to improve
      sensitivity. RESULTS: Arrhythmogenic right ventricular cardiomyopathy is a
      desmosomal disease. Mutations have been detected in five desmosomal genes, most
      frequently in plakophilin-2 (PKP2) and multiple mutations are also reported.
      Antiarrhythmic drugs such as sotalol and amiodarone may improve symptoms but are
      unproven to increase survival. An implantable defibrillator is appropriate in
      individuals surviving cardiac arrest or sustained ventricular tachycardia, but
      there is not yet consensus about prophylactic treatment of Task Force positive
      but asymptomatic individuals. CONCLUSIONS: Arrhythmogenic right ventricular
      cardiomyopathy is more common than previously believed. Preliminary evidence
      supports improved sensitivity without loss of specificity using the revised Task
      Force criteria. The genetics of the disease are complex but should ultimately
      advance diagnosis and management.

PMID- 21885339
TI  - Cardiac genetic investigation of young sudden unexplained death and resuscitated
      out of hospital cardiac arrest.
AB  - Nearly 30% of young sudden deaths have negative autopsies and these sudden
      unexplained deaths (SUDs) are presumed to be due to heritable cardiac arrhythmias
      attributed to cardiac ion channel disorders. Comprehensive cardiac and genetic
      testing of families of SUD is helpful in the detection of inherited cardiac
      genetic conditions. It frequently provides a clue to the cause of death in SUD
      victims and allows early diagnosis and opportunities to prevent SUD in other
      family members. Out of Hospital Cardiac Arrest (OHCA) victims and their families
      also require similar assessment, although the role of genetic testing in this
      group should be reserved to patients where a clinical diagnosis is established. A
      team approach with multidisciplinary specialised clinics and increased access to
      genetic analysis is very helpful in achieving these goals.

PMID- 21885340
TI  - Guidelines for the diagnosis and management of familial dilated cardiomyopathy.
AB  - Dilated cardiomyopathy (DCM) is a myocardial disorder that is a major cause of
      heart failure and death. Recent data indicate that genetic factors are important
      in the pathogenesis of DCM and may account for at least one-third of cases of
      "idiopathic" DCM. Apart from a positive family history, there are no specific
      clinical manifestations that reliably distinguish familial from non-familial DCM,
      and phenotypic features may vary between families and within members of a single
      family. Clinical screening with ECG and echocardiography of all first-degree
      relatives of index cases with "idiopathic" DCM is strongly recommended to
      identify familial disease and to determine the number of affected individuals
      within families. Molecular genetics studies have shown that familial DCM is a
      genetically-heterogeneous disorder with nearly 40 chromosomal loci and disease
      genes identified to date. Mutations in the known disease genes occur relatively
      infrequently however. Although commercial genetic testing for selected disease
      genes is available, the cost and low yield have limited its widespread use. The
      development of next-generation sequencing technologies promises to expedite the
      discovery of new DCM disease genes and help to take genetic testing from the
      research laboratory into routine clinical practice. Affected individuals should
      receive standard pharmacological therapy according to the severity of symptoms
      and signs of heart failure. Asymptomatic family members should undergo periodic
      echocardiographic screening to detect early signs of disease. The optimal
      management of asymptomatic individuals with suspected early disease is not yet
      established.

PMID- 21885341
TI  - Breakthroughs in the genetics of orofacial clefting.
AB  - Nonsyndromic orofacial clefts have a multifactorial etiology, involving both
      genetic and environmental factors. Although linkage and candidate gene studies
      have attempted to elucidate the underlying genetic architecture, only the
      interferon regulatory factor 6 (IRF6) gene has been identified as causative. The
      recent introduction of high-throughput genotyping technologies has enabled
      researchers to perform genome-wide association studies (GWAS). Four GWAS of
      nonsyndromic cleft lip with or without cleft palate have been conducted, and
      these have identified five new chromosomal loci. One locus, located in an
      intergenic region of chromosome 8q24, has been implicated in all GWAS and
      constitutes a major susceptibility locus. This review describes the latest
      genetic findings for nonsyndromic orofacial clefts and discusses their biological
      and functional implications.

PMID- 21885342
TI  - Epigenetic mechanisms in systemic lupus erythematosus and other autoimmune
      diseases.
AB  - The pathogenic origin of autoimmune diseases can be traced to both genetic
      susceptibility and epigenetic modifications arising from exposure to the
      environment. Epigenetic modifications influence gene expression and alter
      cellular functions without modifying the genomic sequence. CpG-DNA methylation,
      histone tail modifications and microRNAs (miRNAs) are the main epigenetic
      mechanisms of gene regulation. Understanding the molecular mechanisms that are
      involved in the pathophysiology of autoimmune diseases is essential for the
      introduction of effective, target-directed and tolerated therapies. In this
      review, we summarize recent findings that signify the importance of epigenetic
      modifications in autoimmune disorders while focusing on systemic lupus
      erythematosus. We also discuss future directions in basic research, autoimmune
      diagnostics and applied therapy.

PMID- 21885343
TI  - An eye on RNAi in nematode parasites.
AB  - RNA interference (RNAi) has revolutionised approaches to gene function
      determination. From a parasitology perspective, gene function studies have the
      added dimension of providing validation data, increasingly deemed essential to
      the initial phases of drug target selection, pre-screen development. Notionally
      advantageous to those working on nematode parasites is the fact that
      Caenorhabditis elegans research spawned RNAi discovery and continues to seed our
      understanding of its fundamentals. Unfortunately, RNAi data for nematode
      parasites illustrate variable and inconsistent susceptibilities which undermine
      confidence and exploitation. Now well-ensconced in an era of nematode parasite
      genomics, we can begin to unscramble this variation.

PMID- 21885344
TI  - Effect of body mass index on IVF treatment outcome: an updated systematic review
      and meta-analysis.
AB  - There is conflicting evidence regarding the effect of raised body mass index
      (BMI) on the outcome of assisted reproductive technology. In particular, there is
      insufficient evidence to describe the effect of BMI on live birth rates. We
      carried out a systematic review and meta-analysis of studies to evaluate the
      effect of raised BMI on treatment outcome following IVF/ICSI treatment. Subgroup
      analysis on overweight and obese patients was performed. Literature searches were
      conducted on MEDLINE, EMBASE and the Web of Science from 1966 to 2010. Thirty
      three studies including 47,967 treatment cycles were included. Results indicated
      that women who were overweight or obese (BMI >= 25) had significantly lower
      clinical pregnancy (RR=0.90, P<0.0001) and live birth rates (RR=0.84, P=0.0002)
      and significantly higher miscarriage rate (RR=1.31, P < 0.0001) compared to women
      with a BMI < 25 following treatment. A subgroup analysis of overweight women (BMI
      >= 25-29.9) revealed lower clinical pregnancy (RR=0.91, P=0.0003) and live birth
      rates (RR=0.91, P=0.01) and higher miscarriage rate (RR=1.24, P < 0.00001)
      compared to women with normal weight (BMI < 25). In conclusion, raised BMI is
      associated with adverse pregnancy outcome in women undergoing IVF/ICSI treatment,
      including lower live birth rates. This effect is present in overweight as well as
      obese women.

PMID- 21885345
TI  - Thrombotic microangiopathy.
AB  - Thrombotic microangiopathy (TMA) is a histopathological feature of various
      diseases including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic
      syndrome (HUS). There are many secondary causes of TMA, many of them could mimic
      TTP or HUS. This article presents a short overview on TMA. In conclusion TMA is
      the result of various etiology reasons and pathologic reactions with various
      clinical entities. It is important to focus on a thorough history including
      family history when deciding on a diagnosis. Analysis of ADAMTS 13 and ADAMTS 13
      antibodies may help to decide continued therapy.

PMID- 21885346
TI  - Rare and common LRRK2 exonic variants in Parkinson's disease.

PMID- 21885349
TI  - Mesial temporal seizures may enhance complex reaction time test performance.
AB  - OBJECTIVE: Probing of cognitive functions during seizures is an underdeveloped
      area of clinical epileptology. Transient cognitive impairment occurs sometime
      after electrographic onset in certain localization-related epilepsies, but
      precisely when and what alterations ensue are unknown. Answers to these questions
      were sought in the context of assessment of feasibility of automated seizure
      warning. METHODS: Subjects undergoing evaluation for invasive epilepsy surgery
      were administered a complex reaction time test triggered automatically by the
      detection of seizures. Performance during seizures was compared during randomly
      chosen interictal periods, using the Kolmogorov-Smirnov test. RESULTS:
      Statistically significant improvement in the performance of certain test metrics
      was observed in 3 of 14 subjects during seizures of mesial temporal lobe origin.
      CONCLUSION: Based on these data, it is plausible that activation of central
      noradrenergic and dopaminergic networks by ictal activity originating from mesial
      temporal structures may, under particular conditions, optimize certain complex
      reaction time responses. If reproduced, these findings would a force a revision
      of the binary tenet that seizures either degrade or spare cognitive functions and
      open unsuspected research vistas.

PMID- 21885350
TI  - To evacuate or shelter in place: implications of universal hurricane evacuation
      policies on nursing home residents.
AB  - OBJECTIVE: To examine the differential morbidity/mortality associated with
      evacuation versus sheltering in place for nursing home (NH) residents exposed to
      the 4 most recent Gulf hurricanes. METHODS: Observational study using Medicare
      claims and NH data sources. We compared the differential mortality/morbidity for
      long-stay residents exposed to 4 recent hurricanes (Katrina, Rita, Gustav, and
      Ike) relative to those residing at the same NHs over the same time periods during
      the prior 2 nonhurricane years as a control. Using an instrumental variable
      analysis, we then evaluated the independent effect of evacuation on outcomes at
      90 days. RESULTS: Among 36,389 NH residents exposed to a storm, the 30- and 90
      day mortality/hospitalization rates increased compared with nonhurricane control
      years. There were a cumulative total of 277 extra deaths and 872 extra
      hospitalizations at 30 days. At 90 days, 579 extra deaths and 544 extra
      hospitalizations were observed. Using the instrumental variable analysis,
      evacuation increased the probability of death at 90 days from 2.7% to 5.3% and
      hospitalization by 1.8% to 8.3%, independent of other factors. CONCLUSION: Among
      residents exposed to hurricanes, evacuation significantly exacerbated subsequent
      morbidity/mortality.

PMID- 21885351
TI  - Interactions of visual and cognitive stress.
AB  - BACKGROUND: The objective of this research is to assess the ocular and muscular
      response to long-duration reading under different visual and cognitive difficulty
      levels. METHODS: Thirty-five subjects, with 20/20 vision and without history of
      ocular pathology or cognitive deficits, participated in the study. Subjects read
      under different visual and cognitive difficulty levels for 6 (30-minute)
      conditions. Upper and lower orbicularis oculi, frontalis, and trapezius muscle
      activities were recorded using surface electromyography (EMG). Aperture size,
      pupil diameter, and pulse rate of the subjects were recorded with a video camera,
      pulse meter, and ISCAN eye tracker (ISCAN Inc.), respectively. RESULTS: The
      results show that the texts read with a refractive error caused increased
      orbicularis oculi EMG power and reduced aperture size (P < 0.001). There was no
      statistically significant difference between the conditions for pulse rate, pupil
      diameter, or EMG activity of the frontalis and trapezius muscles with either
      visual or cognitive stress presented in this experiment. CONCLUSION: Visual
      stress experienced due to reading under an induced refractive error is
      potentially mediated by a local mechanism, different from the mechanism
      underlying reading under low contrast or high cognitive demand.

PMID- 21885352
TI  - Outlook for development of high-throughput cryopreservation for small-bodied
      biomedical model fishes.
AB  - With the development of genomic research technologies, comparative genome studies
      among vertebrate species are becoming commonplace for human biomedical research.
      Fish offer unlimited versatility for biomedical research. Extensive studies are
      done using these fish models, yielding tens of thousands of specific strains and
      lines, and the number is increasing every day. Thus, high-throughput sperm
      cryopreservation is urgently needed to preserve these genetic resources. Although
      high-throughput processing has been widely applied for sperm cryopreservation in
      livestock for decades, application in biomedical model fishes is still in the
      concept-development stage because of the limited sample volumes and the
      biological characteristics of fish sperm. High-throughput processing in livestock
      was developed based on advances made in the laboratory and was scaled up for
      increased processing speed, capability for mass production, and uniformity and
      quality assurance. Cryopreserved germplasm combined with high-throughput
      processing constitutes an independent industry encompassing animal breeding,
      preservation of genetic diversity, and medical research. Currently, there is no
      specifically engineered system available for high-throughput of cryopreserved
      germplasm for aquatic species. This review is to discuss the concepts and needs
      for high-throughput technology for model fishes, propose approaches for technical
      development, and overview future directions of this approach.

PMID- 21885353
TI  - A size barrier limits protein diffusion at the cell surface to generate lipid
      rich myelin-membrane sheets.
AB  - The insulating layers of myelin membrane wrapped around axons by oligodendrocytes
      are essential for the rapid conduction of nerve impulses in the central nervous
      system. To fulfill this function as an electrical insulator, myelin requires a
      unique lipid and protein composition. Here we show that oligodendrocytes employ a
      barrier that functions as a physical filter to generate the lipid-rich myelin
      membrane sheets. Myelin basic protein (MBP) forms this molecular sieve and
      restricts the diffusion of proteins with large cytoplasmic domains into myelin.
      The barrier is generated from MBP molecules that line the entire sheet and is,
      thus, intimately intertwined with the biogenesis of the polarized cell surface.
      This system might have evolved in oligodendrocytes in order to generate an
      anisotropic membrane organization that facilitates the assembly of highly
      insulating lipid-rich membranes.

PMID- 21885347
TI  - Association of LRRK2 exonic variants with susceptibility to Parkinson's disease:
      a case-control study.
AB  - BACKGROUND: Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours
      highly penetrant mutations that are linked to familial parkinsonism. However, the
      extent of its polymorphic variability in relation to risk of Parkinson's disease
      (PD) has not been assessed systematically. We therefore assessed the frequency of
      LRRK2 exonic variants in individuals with and without PD, to investigate the role
      of the variants in PD susceptibility. METHODS: LRRK2 was genotyped in patients
      with PD and controls from three series (white, Asian, and Arab-Berber) from sites
      participating in the Genetic Epidemiology of Parkinson's Disease Consortium.
      Genotyping was done for exonic variants of LRRK2 that were identified through
      searches of literature and the personal communications of consortium members.
      Associations with PD were assessed by use of logistic regression models. For
      variants that had a minor allele frequency of 0.5% or greater, single variant
      associations were assessed, whereas for rarer variants information was collapsed
      across variants. FINDINGS: 121 exonic LRRK2 variants were assessed in 15 540
      individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients
      and 962 controls, and 240 Arab-Berber patients and 372 controls. After exclusion
      of carriers of known pathogenic mutations, new independent risk associations were
      identified for polymorphic variants in white individuals (M1646T, odds ratio
      1.43, 95% CI 1.15-1.78; p=0.0012) and Asian individuals (A419V, 2.27, 1.35-3.83;
      p=0.0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency
      greater than 5% in the white and Asian series, with a similar finding in the Arab
      Berber series (combined odds ratio 0.82, 0.72-0.94; p=0.0043). Of the two
      previously reported Asian risk variants, G2385R was associated with disease
      (1.73, 1.20-2.49; p=0.0026), but no association was noted for R1628P (0.62, 0.36
      1.07; p=0.087). In the Arab-Berber series, Y2189C showed potential evidence of
      risk association with PD (4.48, 1.33-15.09; p=0.012). INTERPRETATION: The results
      for LRRK2 show that several rare and common genetic variants in the same gene can
      have independent effects on disease risk. LRRK2, and the pathway in which it
      functions, is important in the cause and pathogenesis of PD in a greater
      proportion of patients with this disease than previously believed. These results
      will help discriminate those patients who will benefit most from therapies
      targeted at LRRK2 pathogenic activity. FUNDING: Michael J Fox Foundation and
      National Institutes of Health.

PMID- 21885354
TI  - The response of mammalian cells to UV-light reveals Rad54-dependent and
      independent pathways of homologous recombination.
AB  - Ultraviolet (UV) radiation-induced DNA lesions can be efficiently repaired by
      nucleotide excision repair (NER). However, NER is less effective during
      replication of UV-damaged chromosomes. In contrast, translesion DNA synthesis
      (TLS) and homologous recombination (HR) are capable of dealing with lesions in
      replicating DNA. The core HR protein in mammalian cells is the strand exchange
      protein RAD51, which is aided by numerous proteins, including RAD54. We used
      RAD54 as a cellular marker for HR to study the response of mammalian embryonic
      stem (ES) cells to UV irradiation. In contrast to yeast, ES cells lacking RAD54
      are not UV sensitive. Here we show that the requirement for mammalian RAD54 is
      masked by active NER. By genetically inactivating NER and HR through disruption
      of the Xpa and Rad54 genes, respectively, we demonstrate the contribution of HR
      to chromosomal integrity upon UV irradiation. We demonstrate using chromosome
      fiber analysis at the individual replication fork level, that HR activity is
      important for the restart of DNA replication after induction of DNA damage by UV
      light in NER-deficient cells. Furthermore, our data reveal RAD54-dependent and 
      independent contributions of HR to the cellular sensitivity to UV-light, and they
      uncover that RAD54 can compensate for the loss of TLS polymerase eta with regard
      to UV-light sensitivity. In conclusion, we show that HR is important for the
      progression of UV-stalled replication forks in ES cells, and that protection of
      the fork is an interplay between HR and TLS.

PMID- 21885355
TI  - Increased hepatitis C viral load and reactivation of liver disease in HCV RNA
      positive patients with onco-haematological disease undergoing chemotherapy.
AB  - AIMS: To evaluate changes in Hepatitis C Virus (HCV) RNA both in plasma and
      Peripheral Blood Mononuclear Cells (PBMC) in onco-haematological patients.
      PATIENTS AND METHODS: 8 consecutive anti-HCV/HCV RNA-positive patients with onco
      haematological diseases (5 with B-cell Non-Hodgkin Lymphoma and 3 with chronic
      lymphocytic leukaemia) were observed during chemotherapy and after its
      discontinuation. All were naive to chemotherapy. HCV RNA was sought by Real Time
      Polymerase Chain Reaction in Light Cycler 1.5 in plasma and PBMC samples
      collected before, during and after chemotherapy. RESULTS: An increase in HCV RNA
      of at least 1.5 log IU/mL in plasma and 1.1 log IU/ml in PBMC was observed in all
      7 patients undergoing Rituximab-based chemotherapy; these patients showed a
      hepatic flare after discontinuation, life-threatening in one with cirrhosis. Also
      the 8th patient had cirrhosis, but was treated with Rituximab-sparing
      chemotherapy and did not show any increase in HCV RNA or a hepatic flare.
      CONCLUSION: Rituximab-based chemotherapy favours an increase in HCV RNA in onco
      haematological patients; this is followed by a hepatic flare, possibly immune
      mediated and life threatening in cirrhotic patients.

PMID- 21885356
TI  - Shift in chicken intestinal gene association networks after infection with
      Salmonella.
AB  - A primary infection of Salmonella enteritidis causes a spatial-temporal dependent
      change in the gene expression patterns in the intestine of chickens (Gallus
      gallus). This is the result of a dynamic intestinal response to adapt to the
      altered environment and to optimize its 'health' and functionality under the new
      circumstances. By inferring gene association networks (GANs), the complexities of
      and changes in biological networks can be uncovered. Within such GANs highly
      interacting (hub) genes can be identified, which are supposed to be high-level
      regulators connected to multiple processes. By exploring the intestinal
      expression of genes differing between control and Salmonella infected chicken in
      a time-dependent manner differences in GANs were found. In control chickens more
      developmental processes were observed, whereas in infected chickens relatively
      more processes were associated to 'defense/pathogen response'. Moreover the
      conserved protein domains of the identified hub genes in controls were nuclear
      associated, whereas hub genes in infected chickens were involved in 'cellular
      communication'. The shift in topology and functionality of the intestinal GANs in
      control and Salmonella infected animals and the identification of GAN-specific
      hubs is a first step to understand the complexity of biological networks and
      processes regulating intestinal health and functionality under normal and
      disturbed conditions.

PMID- 21885357
TI  - Responses of threespine stickleback (Gasterosteus aculeatus, L) transcriptome to
      hypoxia.
AB  - Hypoxia is a naturally occurring phenomenon in aquatic systems. Its occurrence is
      potentiated by eutrophication caused by human actions and it may be made even
      more severe as a result of increasing temperatures due to climate change.
      Threespine stickleback (Gasterosteus aculeatus) has previously been used by
      ecologists and evolutionary biologists, but has great potential also for
      physiological studies. We subjected threespine sticklebacks to hypoxia (air
      saturation 24-28%) or normoxia for 3 and 48 h. To study changes in the
      transcriptome, microarray determinations were carried out for the 48 h treatments
      and complementary real-time quantitative PCR was run on selected transcripts at
      both time points. The microarray results suggest downregulation of genes encoding
      proteins with functions typically inhibited by hypoxia, i.e., cell proliferation,
      DNA replication and repair, and protein degradation, and upregulation of
      transcripts with products having oxygenase and oxidase activities including two 2
      oxoglutarate-deoxygenases. These transcripts encode for JmjC domain containing
      proteins JMJD6 and JMJD2C. JMJD6 transcription has not earlier been characterized
      to change in hypoxia. Cyp1A2 mRNA was also increased in the microarray and the
      upregulation could be confirmed on protein level by measuring ethoxyresorufin-O
      deethlyase (EROD)-activity.

PMID- 21885358
TI  - Histological evolution of chronic wounds under negative pressure therapy.
AB  - BACKGROUND: Negative pressure wound therapy (NPT) has achieved widespread success
      in the treatment of difficult wounds. However, its effects are but partially
      explored, and investigations mostly concentrated at the wound-dressing interface;
      a detailed histological description of the evolution of wounds under NPT is still
      lacking. MATERIALS AND METHODS: Subsequent punch biopsies of NPT-treated chronic
      wounds of human patients were analysed. Phenomena occurring in wounds were
      quantified by analysis of proliferating cells nuclear antigen (PCNA)
      (proliferating nuclei), CD31 (blood vessels), CD68p (macrophages) and CD45
      (lymphocytes) stained slides. RESULTS: Three layers were identified in day-0
      wounds. Over time, under NPT, the layers behaved differently: the most
      superficial (1.5 mm) developed granulation tissue, constant in thickness, with
      high proliferation index, increased in blood vessels density and developed acute
      inflammation. Instead, the two deeper layers decreased in proliferation rate,
      maintained vessels density unchanged, were cleared of chronic inflammation and
      oedema and underwent progression towards stable tissue. DISCUSSION: Indeed, while
      most research has focused on induction of superficial granulation tissue by NPT,
      deeper layers appear to be also affected, with relieving of chronic inflammation
      and tissue stabilisation. This may be an important and under-appreciated effect,
      playing a role in the known positive outcomes of NPT, such as better graft-taking
      rates.

PMID- 21885359
TI  - Clinical outcome in a series of 173 cases of foreign body granuloma: improved
      outcomes with a novel surgical technique.
AB  - BACKGROUND: Soft-tissue filler injections have become popular, and injections of
      even illegal materials are widespread. Complications such as foreign body
      granuloma often occur in such cases, and appropriate treatment is mandatory but
      no optimal treatment has been established. METHODS: We treated 173 patients who
      underwent surgical excision of foreign body granulomas via direct approach to the
      lesion (n = 121) or injection therapies (n = 52) at Kangbuk Samsung Hospital over
      a period of 7 years from April 2004 to February 2011. A retrospective chart
      review found that 104 patients had a history of treatment failure at other
      hospitals. Among these 104 patients, 83 had a history of prior injection therapy
      and 21 patients had a history of prior surgical therapy. Patient satisfaction was
      evaluated at our hospital on a scale of 1-5 using an in-house questionnaire.
      Comparisons between patients receiving injection therapy and patients receiving
      surgical therapy were made using the Mann-Whitney test. RESULTS: Patients who
      underwent surgical therapy via direct approach to the lesion reported
      statistically higher satisfaction scores 4(3-4) than those who underwent
      injection therapy 3(2-3) (p < 0.001). CONCLUSIONS: Our novel surgical technique
      results in better outcomes and patient satisfaction in cases of severe foreign
      body granuloma.

PMID- 21885360
TI  - Craniofacial repercussions in maxillary lateral incisors agenesis.
AB  - OBJECTIVES: Assessment of the influence of maxillary lateral incisor agenesis
      (MLIA) on the facial morphogenesis. METHODS: Evaluation of the skeletal
      dimensions of the upper maxilla and its incisor region. Analysis was performed
      among three groups: individuals with MLIA, its relatives and the normal
      population. Among these a comparison between adults and growing individuals was
      performed. RESULTS: MLIA may interfere with the maxillary length and the
      anterosuperior facial height, negatively conditioning on its potential growth.
      MLIA was not correlated with changes of the palatine plane inclination, maxillary
      height nor with adjustment of the anterior nasal spine dimensions related to the
      Frankfurt plan or to the posterior nasal spine-Frankfurt plan during the observed
      development stage; the backward angle of the incisors in children with bilateral
      agenesis of lateral incisors appear to have been corrected in adulthood.
      CONCLUSIONS: MLIA is associated with an upper maxilla shortening, and appear to
      interfere significantly with the anterior facial height, reducing its potential
      size.

PMID- 21885362
TI  - Automatable full demineralization DNA extraction procedure from degraded skeletal
      remains.
AB  - During the 7 year period from 2002 to 2009 a high volume, silica-binding DNA
      extraction protocol for bone, based on modified QIAGEN's Blood Maxi Kit protocol
      was highly successful permitting the DNA matching of >14,500 missing persons from
      former Yugoslavia. This method, however, requires large amount of bone material
      and large volumes of reagents. The logical evolution was to develop a more
      efficient extraction protocol for bone samples that uses significantly less
      starting material while increasing the success in obtaining DNA results from
      smaller, more challenging samples. In this study we compared the performance of
      ICMP's original protocol against an automatable full demineralization approach.
      In order to provide reliable results and to simulate a wide variety of cases, we
      analyzed 40 bone samples in a comparative study based on DNA concentrations and
      quality of resulting STR profiles. The new protocol results in the dissolution of
      the entire bone powder sample, thus eliminating the possibility that DNA is left
      behind, locked in remaining solid bone matrix. For the majority of samples
      tested, the DNA concentrations obtained from half a gram of fully digested bone
      material were equivalent to or greater than the ones obtained from 2g of
      partially demineralized bone powder. Furthermore, the full demineralization
      process significantly increases the proportion of full profiles reflecting the
      correlation with better DNA quality. This method has been adapted for the QIAcube
      robotic platform. The performance of this automated full demineralization
      protocol is similar to the manual version and increases overall lab throughput.
      It also simplifies the process by eliminating quality control procedures that are
      advisable in manual procedures, and overall reduces the chance of human error.
      Finally we described a simple and efficient post-extraction clean-up method that
      can be applied to DNA extracts obtained from different protocols. This protocol
      has also been adjusted for the QIAcube platform.

PMID- 21885363
TI  - Acute appendicitis and ectopic pregnancy? Which came first?

PMID- 21885364
TI  - Soave procedure.

PMID- 21885365
TI  - Surgical management of sporadic medullary thyroid cancer.
AB  - Inherited and sporadic medullary thyroid cancer (MTC) is a rare carcinoma.
      Sporadic MTCs represent 70% of cases. Diagnosis is currently made with the
      routine use of serum calcitonin (CT) measurements to screen patients with nodular
      thyroid disease. Surgery is the only curative treatment of MTC and since cervical
      lymph nodes metastases are frequent and can occur at an early stage, a
      standardized lymph node dissection should be associated to total thyroidectomy.
      However, the extent of lymphadenectomy remains debated. Prognosis of MTC is
      related to both the stage of the disease and the extent of initial surgery. When
      tumor remnants persist after surgery, there are very few therapeutic
      alternatives, and these are generally of limited curative value.

PMID- 21885366
TI  - Warm reception? Halogenated BPA flame retardants and PPARgamma activation.

PMID- 21885367
TI  - Climate change & infectious disease: is the future here?

PMID- 21885369
TI  - Environmental factors develop different patterns of immune disease.

PMID- 21885371
TI  - Thirdhand smoke in review: research needs and recommendations.

PMID- 21885372
TI  - Testing the dose addition hypothesis: the impact of pyrethroid insecticide
      mixtures on neurons.

PMID- 21885373
TI  - Scorecard rates emission reductions of hybrid vehicles.

PMID- 21885374
TI  - Dietary intervention and DEHP reduction.

PMID- 21885375
TI  - Fields and forests in flames: vegetation smoke & human health.

PMID- 21885376
TI  - In vitro detection of estrogen activity in plastic products using a sensitive
      bioassay: failure to acknowledge limitations.

PMID- 21885377
TI  - Climate change impacts indoor environment.

PMID- 21885381
TI  - Ambient air pollution and infant health: home monitors make cardiorespiratory
      connections.

PMID- 21885380
TI  - Prenatal exposure to BPA and sexually selected traits in male mice.

PMID- 21885382
TI  - Transportation noise and blood pressure in a population-based sample of adults.
AB  - BACKGROUND: There is some evidence for an association between traffic noise and
      ischemic heart disease; however, associations with blood pressure have been
      inconsistent, and little is known about health effects of railway noise.
      OBJECTIVES: We aimed to investigate the effects of railway and traffic noise
      exposure on blood pressure; a secondary aim was to address potentially
      susceptible subpopulations. METHODS: We performed adjusted linear regression
      analyses using data from 6,450 participants of the second survey of the Swiss
      Study on Air Pollution and Lung Disease in Adults (SAPALDIA 2) to estimate the
      associations of daytime and nighttime railway and traffic noise (A-weighted
      decibels) with systolic blood pressure (SBP) and diastolic blood pressure (DBP;
      millimeters of mercury). Noise data were provided by the Federal Office for the
      Environment. Stratified analyses by self-reported hypertension, cardiovascular
      disease (CVD), and diabetes were performed. RESULTS: Mean noise exposure during
      the day and night was 51 dB(A) and 39 dB(A) for traffic noise, respectively, and
      19 dB(A) and 17 dB(A) for railway noise. Adjusted regression models yielded
      significant effect estimates for a 10 dB(A) increase in railway noise during the
      night [SBP beta = 0.84; 95% confidence interval (CI): 0.22, 1.46; DBP beta =
      0.44; 95% CI: 0.06, 0.81] and day (SBP beta = 0.60; 95% CI: 0.07, 1.13).
      Additional adjustment for nitrogen dioxide left effect estimates almost
      unchanged. Stronger associations were estimated for participants with chronic
      disease. Significant associations with traffic noise were seen only among
      participants with diabetes. CONCLUSION: We found evidence of an adverse effect of
      railway noise on blood pressure in this cohort population. Traffic noise was
      associated with higher blood pressure only in diabetics, possibly due to low
      exposure levels. The study results imply more severe health effects by
      transportation noise in vulnerable populations, such as adults with hypertension,
      diabetes, or CVD.

PMID- 21885383
TI  - The impact of heat islands on mortality in Paris during the August 2003 heat
      wave.
AB  - BACKGROUND: Heat waves have a drastic impact on urban populations, which could
      increase with climate change. OBJECTIVES: We evaluated new indicators of elderly
      people's exposure to heat in Paris, from a public health prevention perspective,
      using satellite thermal images. METHODS: We used a time series of 61 images from
      the satellites of the National Oceanic and Atmospheric Administration's (NOAA)
      Advanced Very High Resolution Radiometer (AVHRR) taken from 1 to 13 August 2003
      to produce thermal indicators of minimum, maximum, and mean surface temperatures
      and diurnal temperature amplitude, with different lags between the meteorological
      data and the health impact. Health data came from a case-control study involving
      241 people >= 65 years of age who died in the city of Paris or the nearby
      suburban area of Val-de-Marne during the August 2003 heat wave, and 241 controls
      who were matched to cases on age, sex, and residential zone. For each person, we
      integrated the thermal indicators in a conditional logistic regression model,
      adjusted for age and other potential confounders. We computed odds ratios (ORs)
      comparing the 90th and 50th percentiles of the temperature differences between
      cases and controls for various indicators. RESULTS: Mortality risk was
      significantly associated with exposure for two indicators: minimum temperatures
      averaged for 1-13 August [for a 0.41 degrees C increase, OR = 2.17; 95%
      confidence interval (CI): 1.14, 4.16] and minimum temperature averaged on the day
      of death and the 6 preceding days (for a 0.51 degrees C increase: OR = 2.24; 95%
      CI: 1.03, 4.87). CONCLUSIONS: Our results support the influence of night
      temperatures on the health impact of heat waves in urban areas. Urban heat
      exposure indicators based on satellite imagery have the potential to identify
      areas with higher risk of death, which could inform intervention decisions by key
      stakeholders.

PMID- 21885385
TI  - Pulmonary infections in HIV-infected patients: an update in the 21st century.
AB  - From the first descriptions of HIV/AIDS, the lung has been the site most
      frequently affected by the disease. Most patients develop a pulmonary
      complication during the history of HIV infection, mainly of infectious aetiology.
      Important changes in the epidemiology of HIV-related pulmonary infections have
      occurred. Overall, prescription of Pneumocystis jirovecii prophylaxis and the
      introduction of highly active antiretroviral therapy (HAART) are the main causes.
      Currently, the most frequent diagnosis in developed countries is bacterial
      pneumonia, especially pneumococcal pneumonia, the second most frequent cause is
      Pneumocystis pneumonia and the third is tuberculosis. However, in Africa,
      tuberculosis could be the most common pulmonary complication of HIV. Pulmonary
      infections remain one of the most important causes of morbidity and mortality in
      these patients, and the first cause of hospital admission in the HAART era.
      Achieving an aetiological diagnosis of pulmonary infection in these patients is
      important due to its prognostic consequences.

PMID- 21885384
TI  - Associations of early childhood manganese and lead coexposure with
      neurodevelopment.
AB  - BACKGROUND: Most toxicologic studies focus on a single agent, although this does
      not reflect real-world scenarios in which humans are exposed to multiple
      chemicals. OBJECTIVES: We prospectively studied manganese-lead interactions in
      early childhood to examine whether manganese-lead coexposure is associated with
      neurodevelopmental deficiencies that are more severe than expected based on
      effects of exposure to each metal alone. METHODS: Four hundred fifty-five
      children were enrolled at birth in an longitudinal cohort study in Mexico City,
      provided blood samples, and were followed until 36 months of age. We measured
      lead and manganese at 12 and 24 months and assessed neurodevelopment at 6-month
      intervals from 12 to 36 months of age using Bayley Scales of Infant Development
      II. RESULTS: Mean (+/- SD) blood concentrations at 12 and 24 months were,
      respectively, 24.7 +/- 5.9 MUg/L and 21.5 +/- 7.4 MUg/L for manganese and 5.1 +/-
      2.6 MUg/dL and 5.0 +/- 2.9 MUg/dL for lead. Mixed-effects models, including
      Bayley scores at five time points, showed a significant interaction over time:
      highest manganese quintile * continuous lead; mental development score, beta = 
      1.27 [95% confidence interval (CI): -2.18, -0.37]; psychomotor development score,
      beta = -0.92 (95% CI: -1.76, -0.09). Slopes for the estimated 12-month lead
      effect on 18-month mental development and 24- through 36-month psychomotor
      development scores were steeper for children with high manganese than for
      children with midrange manganese levels. CONCLUSIONS: We observed evidence of
      synergism between lead and manganese, whereby lead toxicity was increased among
      children with high manganese coexposure. Findings highlight the importance of
      understanding health effects of mixed exposures, particularly during potentially
      sensitive developmental stages such as early childhood.

PMID- 21885386
TI  - Titrated oxygen requirement and prognostication in idiopathic pulmonary fibrosis.
AB  - The supplemental oxygen flow rate is a common bedside measure of gas exchange
      impairment. We aimed to determine whether a titrated oxygen requirement (TOR)
      predicted mortality in idiopathic pulmonary fibrosis (IPF). We examined 104
      adults with IPF enrolled in a prospective cohort study and a validation cohort of
      151 adults with a variety of interstitial lung diseases (ILDs). The TOR was
      defined as the lowest oxygen flow rate required to maintain an oxyhaemoglobin
      saturation of 96% while standing. Cox proportional hazards models and time
      dependent receiver operating characteristic curves were used to examine survival
      time. A higher TOR was associated with a greater mortality rate independent of
      forced vital capacity and 6-min walk test results in IPF (adjusted hazard ratio
      (per 1 L.min(-1)) 1.16, 95% CI 1.06-1.27). The TOR was at least as accurate as
      pulmonary function and 6-min walk testing at predicting 1-yr mortality. Findings
      were similar in other ILDs. The TOR is a simple, inexpensive bedside measurement
      that aids prognostication in IPF.

PMID- 21885387
TI  - Chronic infection and inflammation affect exercise capacity in cystic fibrosis.
AB  - Pulmonary function and nutritional status are important determinants of exercise
      capacity in patients with cystic fibrosis (CF). Studies investigating the effects
      of determinants, such as genotype or infection and inflammation, are scarce and
      have never been analysed in a multivariate longitudinal model. A prospective
      longitudinal cohort study was performed to evaluate whether genotype, chronic
      inflammation and infection were associated with changes in exercise capacity.
      Furthermore, we investigated whether exercise capacity can predict clinical
      outcome. 504 exercise tests of 149 adolescents with CF were evaluated. Maximal
      oxygen uptake corrected for body mass % predicted declined 20% during
      adolescence, and was associated with immunoglobulin (Ig)G levels and chronic
      Pseudomonas aeruginosa infection. A lower exercise capacity was associated with a
      higher mortality, steeper decline in pulmonary function and greater increase in
      IgG levels. Since a decline in exercise capacity during adolescence was
      negatively associated with IgG levels and chronic P. aeruginosa infection, these
      data emphasise the importance of prevention and treatment of chronic inflammation
      and infections in patients with CF. Furthermore, a lower exercise capacity was
      associated with a higher mortality rate, steeper decline in pulmonary function
      and higher increase in IgG levels with increasing age in adolescents with CF.
      This stresses the value of regular exercise testing for assessing prognosis in
      adolescents with CF.

PMID- 21885388
TI  - Assessing the Liverpool Respiratory Symptom Questionnaire in children with cystic
      fibrosis.
AB  - Monitoring respiratory status in cystic fibrosis (CF) is challenging,
      particularly in young children. We aimed to test whether the Liverpool
      Respiratory Symptom Questionnaire (LRSQ) could distinguish well, pre-school and
      older children with and without CF, whether it could distinguish well and unwell
      children with CF and, finally, whether LRSQ scores in older children with CF
      correlated with established measures of disease severity. 20 stable pre-school
      children with CF had significantly higher total LRSQ scores than 51 pre-school
      controls, and higher scores in two out of eight domains. Similarly, 21 stable 6-
      to 12-yr-old children with CF had higher total scores than 97 6- to 12-yr-old
      controls, and higher scores in seven out of eight domains. In older children with
      CF, LRSQ scores correlated negatively with Shwachman score and forced expiratory
      volume in 1 s (r = -0.58, p < 0.001, n = 31; and r = -0.46, p < 0.010, n = 34,
      respectively). Within the CF group, patients who cultured Pseudomonas aeruginosa,
      who used more "back-up" antibiotics or whose school attendance was lower also had
      higher LRSQ scores. The LRSQ differentiates well children from those with CF in
      both pre-school and the 6- to 12-yr-old age group, even at a point of stability.
      It also differentiates stable from unwell children with CF, and scores correlate
      with other measures of respiratory disease, highlighting its potential as a
      clinical monitoring tool in paediatric CF.

PMID- 21885389
TI  - Nasal continuous positive airway pressure: influence on digital volume pulse in
      obstructive sleep apnoea patients.
AB  - Obstructive sleep apnoea (OSA) is linked to increased cardiovascular risk. This
      risk can be reduced by nasal continuous positive airway pressure (nCPAP)
      treatment. As OSA is associated with an increase of several vasoconstrictive
      factors, we investigated whether nCPAP influences the digital volume pulse wave.
      We performed digital photoplethysmography during sleep at night in 94 consecutive
      patients who underwent polysomnography and 29 patients treated with nCPAP.
      Digital volume pulse waves were obtained independently of an investigator and
      were quantified using an algorithm for continuous automated analysis. In patients
      with OSA and an apnoea/hypopnoea index (AHI) of >10 events . h(-1), a significant
      vasoconstriction was observed during the night (p<0.0001 by Friedman's test). A
      significant positive correlation existed between vasoconstriction and AHI
      (Spearman correlation, r = 0.27; p<0.01; n = 94) and the arousal index (Spearman
      correlation, r = 0.21; p < 0.05; n = 94). After 6 months of nCPAP treatment, the
      AHI was significantly reduced from 27 +/- 3 events . h(-1) to 4 +/- 2 events . h(
      1) (each n = 29; p<0.001) and vasoconstriction during the night was significantly
      reduced from 10 +/- 3% to 3 +/- 1% (p<0.01). We show changes in the reflective
      index during the night consistent with vasoconstriction in patients with OSA,
      which are significantly reduced after 6 months of nCPAP treatment.

PMID- 21885390
TI  - Intermittent recruitment with high-frequency oscillation/tracheal gas
      insufflation in acute respiratory distress syndrome.
AB  - In acute respiratory distress syndrome (ARDS), recruitment sessions of high
      frequency oscillation (HFO) and tracheal gas insufflation (TGI) with short
      lasting recruitment manoeuvres (RMs) may improve oxygenation and enable reduction
      of subsequent conventional mechanical ventilation (CMV) pressures. We determined
      the effect of adding HFO-TGI sessions to lung-protective CMV on early/severe ARDS
      outcome. We conducted a prospective clinical trial, subdivided into a first
      single-centre period and a second two-centre period. We enrolled 125 (first
      period, n = 54) patients with arterial oxygen tension (P(a,O(2)))/inspiratory
      oxygen fraction (F(I,O(2))) of <150 mmHg for >12 consecutive hours at an end
      expiratory pressure of >= 8 cmH(2)O. Patients were randomly assigned to an HFO
      TGI group (receiving HFO-TGI sessions with RMs, interspersed with lung-protective
      CMV; n = 61) or CMV group (receiving lung-protective CMV and RMs; n = 64). The
      primary outcome was survival to hospital discharge. Pre-enrolment ventilation
      duration was variable. During days 1-10 post-randomisation, P(a,O(2))/F(I,O(2))),
      oxygenation index, plateau pressure and respiratory compliance were improved in
      the HFO-TGI group versus the CMV group (p < 0.001 for group * time). Within days
      1-60, the HFO-TGI group had more ventilator-free days versus the CMV group
      (median (interquartile range) 31.0 (0.0-42.0) versus 0.0 (0.0-23.0) days; p <
      0.001), and more days without respiratory, circulatory, renal, coagulation and
      liver failure (p <= 0.003). Survival to hospital discharge was higher in the HFO
      TGI group versus the CMV group (38 (62.3%) out of 61 versus 23 (35.9%) out of 64
      subjects; p = 0.004). Intermittent recruitment with HFO-TGI and RMs may improve
      survival in early/severe ARDS.

PMID- 21885391
TI  - Respiratory health and endotoxin: associations and modification by CD14/-260
      genotype.
AB  - Exposure to endotoxin has been associated with increased respiratory symptoms and
      decrements in lung function in occupational settings but little is known about
      the health effects of domestic exposure in adults. Here, we describe the
      association of respiratory disease, immunoglobulin (Ig)E sensitisation, bronchial
      reactivity and lung function with mattress endotoxin levels in adults, and
      determine whether these associations are modified by polymorphisms in CD14.
      Endotoxin levels in mattress dust from a population-based sample of 972 adults
      were measured. Associations were examined using generalised linear mixed models,
      adjusting for individual and household confounders. Effect modification of these
      associations by CD14/-260 (rs2569190) was assessed. Mattress endotoxin levels
      varied from 0.1 to 402.6 EU . mg(-1). Although there was no overall association
      of lung function with endotoxin exposure, there was evidence that the association
      of forced expiratory volume in 1 s and forced vital capacity with endotoxin was
      modified by CD14/-260 genotype (p-value for interaction 0.005 and 0.013,
      respectively). There was no evidence that symptoms, IgE sensitisation or
      bronchial reactivity were associated with mattress endotoxin levels. In this
      large epidemiological study of adults, there was no evidence that mattress
      endotoxin level was associated with respiratory symptoms or IgE sensitisation but
      the association of lung function with endotoxin levels may be modified by CD14
      genotype.

PMID- 21885392
TI  - The prognostic impact of follow-up assessments in patients with idiopathic
      pulmonary arterial hypertension.
AB  - Current guidelines for the treatment of patients with idiopathic pulmonary
      arterial hypertension (IPAH) recommend basing therapeutic decision-making on
      haemodynamic, functional and biochemical variables. Most of these parameters have
      been evaluated as risk predictors at the time of diagnosis. The aim of the
      present study was to assess the prognostic impact of changes in these parameters
      after initiation of targeted therapy. A cohort of 109 patients with IPAH who had
      undergone haemodynamic, functional and biochemical assessments at baseline and 3
      12 months after initiation of pulmonary arterial hypertension (PAH)-targeted
      therapy, were followed for a median 38 months in order to determine predictors of
      mortality at baseline and during the course of their disease. Within the
      observation period, 53 (48.6%) patients died and four (3.7%) underwent lung
      transplantation. Kaplan-Meier estimates for transplantation-free survival were
      92%, 67%, and 51% at 1, 3, and 5 yrs, respectively. Among baseline variables, 6
      min walk distance, right atrial pressure, cardiac index, mixed-venous oxygen
      saturation (S(v,O(2))) and N-terminal-pro brain natriuretic peptide (NT-proBNP)
      were independent predictors of survival. During follow-up, changes in World
      Health Organization functional class, cardiac index, S(v,O(2)) and NT-proBNP
      proved significant predictors of outcome. When assigned to prognostic groups,
      improvements as well as deteriorations in these parameters after initiation of
      PAH-targeted therapy had a strong impact on survival. Measurements obtained at
      follow-up had a higher predictive value than variables obtained at baseline.
      Changes in established predictors of outcome during the course of the disease
      provide important prognostic information in patients with IPAH.

PMID- 21885393
TI  - Physiological changes during low- and high-intensity noninvasive ventilation.
AB  - In a physiological randomised cross-over study performed in stable hypercapnic
      chronic obstructive disease patients, we assessed the short-term effects of two
      settings of noninvasive ventilation. One setting was aimed at maximally reducing
      arterial carbon dioxide tension (P(a,CO(2))) (high-intensity (Hi) noninvasive
      positive pressure ventilation (NPPV)): mean +/- SD 27.6 +/- 2.1 cmH(2)O of
      inspiratory positive airway pressure, 4 +/- 0 cmH(2)O of expiratory positive
      airway pressure and respiratory rate of 22 breaths . min(-1). The other was
      performed according to the usual parameters used in earlier studies (low
      intensity (Li)-NPPV): 17.7 +/- 1.6 cmH(2)O of inspiratory positive airway
      pressure, 4 +/- 0 cmH(2)O of expiratory positive airway pressure and respiratory
      rate of 12 breaths . min(-1). Both modes of ventilation significantly improved
      gas exchange compared with spontaneous breathing (SB), but to a greater extent
      using Hi-NPPV (P(a,CO(2)) 59.3 +/- 7.5, 55.2 +/- 6.9 and 49.4 +/- 7.8 mmHg for
      SB, Li-NPPV and Hi-NPPV, respectively). Similarly, Hi-NPPV induced a greater
      reduction in the pressure-time product of the diaphragm per minute from 323 +/-
      149 cmH(2)O . s . min(-1) during SB to 132 +/- 139 cmH(2)O . s . min(-1) during
      Li-NPPV and 40 +/- 69 cmH(2)O . s . min(-1) during Hi-NPPV, while in nine out of
      15 patients, it completely abolished SB activity. Hi-NPPV also induced a marked
      reduction in cardiac output (CO) measured noninvasively with a Finometer PRO
      (Finapres Medical Systems BV, Amsterdam, the Netherlands) compared with Li-NPPV.
      We conclude that while Hi-NPPV is more effective than Li-NPPV in improving gas
      exchange and in reducing inspiratory effort, it induces a marked reduction in CO,
      which needs to be considered when Hi-NPPV is applied to patients with pre
      existing cardiac disease.

PMID- 21885394
TI  - Pulmonary vascular resistances during exercise in normal subjects: a systematic
      review.
AB  - The physiological range of pulmonary vascular resistance (PVR) and total
      pulmonary resistance (TPR), and the impact of exercise, age and posture have been
      a matter of debate for many years. We performed a systematic literature review
      including all right heart catheterisation data where individual PVR and TPR of
      healthy subjects both at rest and exercise were available. Data were stratified
      according to age, exercise level and posture. Supine resting PVR in subjects aged
      <24 yrs, 24-50 yrs, 51-69 yrs and >=70 yrs was 61+/-23, 69+/-28, 86+/-15 and 90+/
      39 dyn.s.cm(-5), respectively. Corresponding TPR was 165+/-50, 164+/-46, 226+/-64
      and 223+/-45 dyn.s.cm(-5), respectively. During moderate exercise in subjects
      aged <=50 yrs, an 85% increase in cardiac output was associated with a 25%
      decrease in TPR (p<0.0001) and a 12% decrease in PVR (p<0.01). At 51-69 yrs of
      age there was no significant decrease in TPR and PVR. In individuals aged >=70
      yrs TPR even increased by 17% (p=0.01), while PVR did not change significantly.
      At higher exercise levels, TPR decreased in all age groups. In the upright
      position, based on a limited number of data, resting TPR and PVR were higher than
      in the supine position and decreased more prominently during exercise, suggesting
      the release of resting pulmonary vasoconstriction. These data may form a basis to
      define normal PVR at rest and exercise.

PMID- 21885396
TI  - Overweight is not a comorbidity factor during childhood asthma: the GrowthOb
      study.
AB  - While being overweight is a risk factor for subsequent asthma in children, the
      importance of body mass index (BMI) as a comorbidity factor remains debated. The
      aim of this study was to assess the relationships between being overweight and
      the characteristics of childhood asthma. The BMI, BMI z-scores and International
      Obesity Task Force (IOTF) grades were evaluated in asthmatic children according
      to atopic status, symptoms during the past 3 months, exercise breathlessness,
      treatment and lung function in 6-15-yr-old children with confirmed asthma. 491
      asthmatic children (mean +/- SD age 10.8 +/- 2.6 yrs; 179 females) were
      prospectively enrolled. There were 78 (15.5%) overweight (IOTF grade 1) and eight
      (1.6%) obese (grade 2) children. The children's BMI z-scores did not differ
      according to atopy, exacerbation, symptom-free days or treatment. The BMI z-score
      correlated positively with forced vital capacity and forced expiratory volume in
      1 s in females, which could be related to earlier puberty in overweight females
      (growth spurt with increased volumes). Compared with normal weight children,
      overweight and obese children had reduced lung volume ratios (functional residual
      capacity/total lung capacity (TLC) and residual volume/TLC), no evidence of
      airflow limitation and similar symptoms. In conclusion, the observed functional
      relationships with BMI are not specific to asthma and being overweight is not
      associated with significant clinical impacts on asthma during childhood.

PMID- 21885397
TI  - Expression of muscarinic receptors by human macrophages.
AB  - Macrophages increase in number and are highly activated in chronic obstructive
      pulmonary disease (COPD). Muscarinic receptor antagonists inhibit acetylcholine
      stimulated release of neutrophilic chemoattractants, suggesting that
      acetylcholine may regulate macrophage responses. Therefore, expression and
      function of components of the non-neuronal cholinergic system in monocyte
      macrophage cells was investigated. RNA was isolated from monocytes, monocyte
      derived macrophages (MDMs), lung and alveolar macrophages from nonsmokers,
      smokers and COPD patients, and expression of the high-affinity choline
      transporter, choline acetyltransferase, vesicular acetylcholine transporter and
      muscarinic receptors (M(1)-M(5)) ascertained using real-time PCR. M(2) and M(3)
      receptor expression was confirmed using immunocytochemistry. Release of
      interleukin (IL)-8, IL-6 and leukotriene (LT)B(4) were measured by ELISA or EIA.
      All monocyte-macrophage cells expressed mRNA for components of the non-neuronal
      cholinergic system. Lung macrophages expressed significantly more M(1) mRNA
      compared with monocytes, and both lung macrophages and alveolar macrophages
      expressed the highest levels of M(3) mRNA. Expression of M(2) and M(3) protein
      was confirmed in MDMs and lung macrophages. Carbachol stimulated release of
      LTB(4) from lung macrophages (buffer 222.3 +/- 75.1 versus carbachol 1,118 +/-
      622.4 pg . mL(-1); n = 15, p<0.05) but not IL-6 or IL-8. LTB(4) release was
      attenuated by the M(3) antagonist, 1,1-dimethyl-4-diphenylacetoxypiperidinium
      iodide (4-DAMP; half maximal effective concentration 5.2 +/- 2.2 nM; n = 9).
      Stimulation of macrophage M(3) receptors promotes release of LTB(4), suggesting
      that anti-muscarinic agents may be anti-inflammatory.

PMID- 21885398
TI  - Sensitive cardiac troponin I predicts poor outcomes in pulmonary arterial
      hypertension.
AB  - Circulating cardiac troponins are markers of myocardial injury. We sought to
      determine whether cardiac troponin I (cTnI), measured by a sensitive assay, is
      associated with disease severity and prognosis in pulmonary arterial hypertension
      (PAH). cTnI was measured in 68 patients with PAH diagnostic category 1 in a
      research-based sensitive immunoanalyser with a lower limit of detection of 0.008
      ng . mL(-1). The associations between cTnI and PAH severity and clinical outcomes
      were assessed using Chi-squared and Wilcoxon rank sum tests, Kaplan-Meier
      analysis and Cox regression models. cTnI was detected in 25% of patients.
      Patients with detectable cTnI had more advanced functional class symptoms, a
      shorter 6-min walk distance, more pericardial effusions, larger right atrial
      area, and higher B-type natriuretic peptide and C-reactive protein levels. 36
      month transplant-free survival was 44% in patients with detectable cTnI versus
      85% in those with undetectable cTnI. cTnI was associated with a 4.7-fold
      increased risk of death related to right ventricular failure or transplant
      (hazard ratio 4.74, 95% CI 1.89-11.89; p<0.001), even when adjusted individually
      for known parameters of PAH severity. Elevated plasma cTnI, even at subclinically
      detectable levels, is associated with more severe disease and worse outcomes in
      patients with PAH.

PMID- 21885395
TI  - Clinical presentation and outcome of venous thromboembolism in COPD.
AB  - Chronic obstructive pulmonary disease (COPD) is a moderate risk factor for venous
      thromboembolism (VTE), but neither the clinical presentation nor the outcome of
      VTE in COPD patients is well known. The clinical presentation of VTE, namely
      pulmonary embolism (PE) or deep venous thrombosis (DVT), and the outcome at 3
      months (death, recurrent VTE or bleeding) were compared between 2,984 COPD
      patients and 25,936 non-COPD patients included in the RIETE (Registro
      Informatizado de la Enfermedad TromboEmbolica) registry. This ongoing
      international, multi-centre registry includes patients with proven symptomatic PE
      or DVT. PE was the more frequent VTE presentation in COPD patients (n = 1,761,
      59%). PE presentation was more significantly associated with COPD patients than
      non-COPD patients (OR 1.64, 95% CI 1.49-1.80). During the 3-month follow-up,
      mortality (10.8% versus 7.6%), minor bleeding (4.5% versus 2.3%) or first VTE
      recurrences as PE (1.5% versus 1.1%) were significantly higher in COPD patients
      than in non-COPD patients. PE was the most common cause of death. COPD patients
      presented more frequently with PE than DVT. It may explain the worse prognosis of
      COPD patients, with a higher risk of death, bleeding or VTE recurrences as PE
      compared with non-COPD patients. Further therapeutic options are needed.

PMID- 21885399
TI  - ASPIRE registry: assessing the Spectrum of Pulmonary hypertension Identified at a
      REferral centre.
AB  - Pulmonary hypertension (PH) is a heterogeneous condition. To date, no registry
      data exists reflecting the spectrum of disease across the five diagnostic groups
      encountered in a specialist referral centre. Data was retrieved for consecutive,
      treatment-naive cases diagnosed between 2001 and 2010 using a catheter-based
      approach. 1,344 patients were enrolled, with a mean follow-up of 2.9 yrs. The 3
      yr survival was 68% for pulmonary arterial hypertension (PAH), 73% for PH
      associated with left heart disease, 44% for PH associated with lung disease (PH
      lung), 71% for chronic thromboembolic PH (CTEPH) and 59% for miscellaneous PH.
      Compared with PAH, survival was inferior in PH-lung and superior in CTEPH
      (p<0.05). Multivariate analysis demonstrated that diagnostic group independently
      predicted survival. Within PAH, Eisenmenger's survival was superior to idiopathic
      PAH, which was superior to PAH associated with systemic sclerosis (p<0.005).
      Within PH-lung, 3-yr survival in sleep disorders/alveolar hypoventilation (90%)
      was superior to PH-lung with chronic obstructive pulmonary disease (41%) and
      interstitial lung disease (16%) (p<0.05). In CTEPH, long-term survival was best
      in patients with surgically accessible disease undergoing pulmonary
      endarterectomy. In this large registry of consecutive, treatment-naive patients
      identified at a specialist PH centre, outcomes and characteristics differed
      between and within PH groups. The current system of classification of PH has
      prognostic value even when adjusted for age and disease severity, emphasising the
      importance of systematic evaluation and precise classification.

PMID- 21885400
TI  - Neutrophil chemotaxis in granulomatosis with polyangiitis (Wegener's) and
      idiopathic pulmonary fibrosis.
AB  - The presence of antineutrophil cytoplasmic antibodies in granulomatosis with
      polyangiitis (Wegener's) (GPA) implicates the neutrophil as a key effector cell.
      Previous studies have reported elevated neutrophil counts in the lung, although
      the determinants of neutrophil chemotaxis in the GPA lung are unknown.
      Bronchoalveolar lavage fluid (BALF) cell counts, myeloperoxidase (MPO) and
      chemokines were measured in 27 patients with GPA, 20 disease controls with
      idiopathic pulmonary fibrosis (IPF) and six healthy controls. CXC chemokine
      ligand (CXCL)8, interleukin (IL)-1beta, epithelial neutrophil-activating protein
      78, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage
      colony-stimulating factor were measured by ELISA. The neutrophil chemotactic
      potential of BALF was investigated using the under-agarose method, and specific
      antibodies were used to examine the role of CXCL8 and IL-1beta. GPA BALF had an
      increased neutrophil percentage, and elevated MPO, CXCL8 and G-CSF concentrations
      compared with healthy controls. Chemotaxis of control neutrophils towards BALF
      from patients with active (p=0.006) and remission (p=0.077) GPA, and IPF
      (p=0.001) patients was increased compared with normal controls. BALF-induced
      chemotaxis correlated with BALF IL-1beta (r=0.761, p=0.001) and CXCL8 (r=0.640,
      p=0.012) in GPA, and was inhibited by anti-CXCL8 (85%; p<0.001) and anti-IL-1beta
      (69%; p<0.001). Our study confirms a neutrophilia and pro-inflammatory alveolar
      milieu that persists in clinical remission. CXCL8 and IL-1beta appear to play
      important roles in the neutrophil chemotactic response to BALF.

PMID- 21885402
TI  - Imaging cardiac arrhythmias.

PMID- 21885403
TI  - Understanding the enemy.
AB  - In this issue of Science Translational Medicine, Tanas and colleagues describe a
      disease-defining genetic alteration for the vascular cancer epithelioid
      hemangioendothelioma (EHE). The resulting EHE-associated fusion gene encodes an
      aberrantly expressed putative transcription factor. This molecular information is
      the latest in a series of genetic discoveries that aid in cancer diagnosis and
      may pave the way to targeted therapeutic agents.

PMID- 21885404
TI  - Identification of a disease-defining gene fusion in epithelioid
      hemangioendothelioma.
AB  - Integrating transcriptomic sequencing with conventional cytogenetics, we
      identified WWTR1 (WW domain-containing transcription regulator 1) (3q25) and
      CAMTA1 (calmodulin-binding transcription activator 1) (1p36) as the two genes
      involved in the t(1;3)(p36;q25) chromosomal translocation that is characteristic
      of epithelioid hemangioendothelioma (EHE), a vascular sarcoma. This WWTR1/CAMTA1
      gene fusion is under the transcriptional control of the WWTR1 promoter and
      encodes a putative chimeric transcription factor that joins the amino terminus of
      WWTR1, a protein that is highly expressed in endothelial cells, in-frame to the
      carboxyl terminus of CAMTA1, a protein that is normally expressed only in brain.
      Thus, CAMTA1 expression is activated inappropriately through a promoter-switch
      mechanism. The gene fusion is present in virtually all EHEs tested but is absent
      from all other vascular neoplasms, demonstrating it to be a disease-defining
      genetic alteration. A sensitive and specific break-apart fluorescence in situ
      hybridization assay was also developed to detect the translocation and will
      assist in the evaluation of this diagnostically challenging neoplasm. The
      chimeric WWTR1/CAMTA1 transcription factor may represent a therapeutic target for
      EHE and offers the opportunity to shed light on the functions of two poorly
      characterized proteins.

PMID- 21885408
TI  - Towards the development of EU/EEA Standards for Tuberculosis Care (ESTC).

PMID- 21885406
TI  - Noninvasive electroanatomic mapping of human ventricular arrhythmias with
      electrocardiographic imaging.
AB  - The rapid heartbeat of ventricular tachycardia (VT) can lead to sudden cardiac
      death and is a major health issue worldwide. Efforts to identify patients at
      risk, determine mechanisms of VT, and effectively prevent and treat VT through a
      mechanism-based approach would all be facilitated by continuous, noninvasive
      imaging of the arrhythmia over the entire heart. Here, we present noninvasive
      real-time images of human ventricular arrhythmias using electrocardiographic
      imaging (ECGI). Our results reveal diverse activation patterns, mechanisms, and
      sites of initiation of human VT. The spatial resolution of ECGI is superior to
      that of the routinely used 12-lead electrocardiogram, which provides only global
      information, and ECGI has distinct advantages over the currently used method of
      mapping with invasive catheter-applied electrodes. The spatial resolution of this
      method and its ability to image electrical activation sequences over the entire
      ventricular surfaces in a single heartbeat allowed us to determine VT initiation
      sites and continuation pathways, as well as VT relationships to ventricular
      substrates, including anatomical scars and abnormal electrophysiological
      substrate. Thus, ECGI can map the VT activation sequence and identify the
      location and depth of VT origin in individual patients, allowing personalized
      treatment of patients with ventricular arrhythmias.

PMID- 21885409
TI  - Sleep HERMES: a European training project for respiratory sleep medicine.

PMID- 21885405
TI  - A computational model to predict the effects of class I anti-arrhythmic drugs on
      ventricular rhythms.
AB  - A long-sought, and thus far elusive, goal has been to develop drugs to manage
      diseases of excitability. One such disease that affects millions each year is
      cardiac arrhythmia, which occurs when electrical impulses in the heart become
      disordered, sometimes causing sudden death. Pharmacological management of cardiac
      arrhythmia has failed because it is not possible to predict how drugs that target
      cardiac ion channels, and have intrinsically complex dynamic interactions with
      ion channels, will alter the emergent electrical behavior generated in the heart.
      Here, we applied a computational model, which was informed and validated by
      experimental data, that defined key measurable parameters necessary to simulate
      the interaction kinetics of the anti-arrhythmic drugs flecainide and lidocaine
      with cardiac sodium channels. We then used the model to predict the effects of
      these drugs on normal human ventricular cellular and tissue electrical activity
      in the setting of a common arrhythmia trigger, spontaneous ventricular ectopy.
      The model forecasts the clinically relevant concentrations at which flecainide
      and lidocaine exacerbate, rather than ameliorate, arrhythmia. Experiments in
      rabbit hearts and simulations in human ventricles based on magnetic resonance
      images validated the model predictions. This computational framework initiates
      the first steps toward development of a virtual drug-screening system that models
      drug-channel interactions and predicts the effects of drugs on emergent
      electrical activity in the heart.

PMID- 21885410
TI  - The European Respiratory Society: future directions in medical education.

PMID- 21885411
TI  - Immune system dysregulation in chronic lung disease.

PMID- 21885412
TI  - Directing the future of lung health: the European Respiratory Roadmap.

PMID- 21885413
TI  - It is time for patients to undergo bronchoscopy without discomfort.

PMID- 21885414
TI  - Whistleblowers.

PMID- 21885415
TI  - Living with pulmonary hypertension: quality not just quantity.

PMID- 21885416
TI  - Rehabilitation in COPD patients: evergreen in pneumology and beyond.

PMID- 21885417
TI  - Mechanisms of dyspnoea relief following radiation treatment in a patient with
      severe COPD.

PMID- 21885419
TI  - A rare pulmonary zygomycosis manifested as chronic mediastinitis and bronchial
      perforation.

PMID- 21885418
TI  - Linezolid safety, tolerability and efficacy to treat multidrug- and extensively
      drug-resistant tuberculosis.

PMID- 21885420
TI  - Pulmonary endarterectomy in sickle cell haemoglobin C disease.

PMID- 21885421
TI  - Cell count and lymphocyte immunophenotyping of bronchoalveolar lavage fluid in
      healthy Brazilian children.

PMID- 21885422
TI  - Clinical relevance of mixed respiratory viral infections in adults with influenza
      A H1N1.

PMID- 21885423
TI  - Does RAGE protect smokers from COPD?

PMID- 21885424
TI  - Can dog allergen alone, if combined with indoor pollution, be responsible for
      asthma in children?

PMID- 21885427
TI  - Interferon-gamma release assays for diagnosis of active pleural tuberculosis: a
      developing world perspective.

PMID- 21885429
TI  - Adipose-selective overexpression of ABHD5/CGI-58 does not increase lipolysis or
      protect against diet-induced obesity.
AB  - Adipose triglyceride lipase (ATGL) catalyzes the first step of triacylglycerol
      hydrolysis in adipocytes. Abhydrolase domain 5 (ABHD5) increases ATGL activity by
      an unknown mechanism. Prior studies have suggested that the expression of ABHD5
      is limiting for lipolysis in adipocytes, as addition of recombinant ABHD5
      increases in vitro TAG hydrolase activity of adipocyte lysates. To test this
      hypothesis in vivo, we generated transgenic mice that express 6-fold higher ABHD5
      in adipose tissue relative to wild-type (WT) mice. In vivo lipolysis increased to
      a similar extent in ABHD5 transgenic and WT mice following an overnight fast or
      injection of either a beta-adrenergic receptor agonist or lipopolysaccharide.
      Similarly, basal and beta-adrenergic-stimulated lipolysis was comparable in
      adipocytes isolated from ABHD5 transgenic and WT mice. Although ABHD5 expression
      was elevated in thioglycolate-elicited macrophages from ABHD5 transgenic mice,
      Toll-like receptor 4 (TLR4) signaling was comparable in macrophages isolated from
      ABHD5 transgenic and WT mice. Overexpression of ABHD5 did not prevent the
      development of obesity in mice fed a high-fat diet, as shown by comparison of
      body weight, body fat percentage, and adipocyte hypertrophy of ABHD5 transgenic
      to WT mice. The expression of ABHD5 in mouse adipose tissue is not limiting for
      either basal or stimulated lipolysis.

PMID- 21885430
TI  - Perilipin 5, a lipid droplet-associated protein, provides physical and metabolic
      linkage to mitochondria.
AB  - Maintaining cellular lipid homeostasis is crucial to oxidative tissues, and it
      becomes compromised in obesity. Lipid droplets (LD) play a central role in lipid
      homeostasis by mediating fatty acid (FA) storage in the form of triglyceride,
      thereby lowering intracellular levels of lipids that mediate cellular
      lipotoxicity. LDs and mitochondria have interconnected functions, and anecdotal
      evidence suggests they physically interact. However, the mechanisms of
      interaction have not been identified. Perilipins are LD-scaffolding proteins and
      potential candidates to play a role in their interaction with mitochondria. We
      examined the contribution of LD perilipin composition to the physical and
      metabolic interactions between LD and mitochondria using multiple techniques:
      confocal imaging, electron microscopy (EM), and lipid storage and utilization
      measurements. Using neonatal cardiomyocytes, reconstituted cell culture models,
      and rodent heart tissues, we found that perilipin 5 (Plin5) recruits mitochondria
      to the LD surface through a C-terminal region. Compared with control cells, Plin5
      expressing cells show decreased LD hydrolysis, decreased palmitate beta
      oxidation, and increased palmitate incorporation into triglycerides in basal
      conditions, whereas in stimulated conditions, LD hydrolysis inhibition is lifted
      and FA released for beta-oxidation. These results suggest that Plin5 regulates
      oxidative LD hydrolysis and controls local FA flux to protect mitochondria
      against excessive exposure to FA during physiological stress.

PMID- 21885432
TI  - Weight loss and melena in an adolescent female.

PMID- 21885433
TI  - Increased documentation and management of pediatric obesity following
      implementation of an EMR upgrade and education.
AB  - BACKGROUND: Overweight children are often not identified or counseled. PURPOSE:
      We assessed the documentation rate and clinical management of overweight children
      before and after an electronic medical record (EMR) upgrade calculating body mass
      index (BMI) percentile for age and gender. METHODS: Family Medicine resident and
      faculty physicians at two sites received an EMR upgrade; Site 1 physicians also
      received BMI training and education. From two years before to one year after the
      upgrade, randomly selected charts were reviewed for all encounters with
      overweight children for documentation of obesity and clinical management.
      RESULTS: After the EMR upgrade, documentation and counseling rates significantly
      improved at both sites but the rate of change was greater for Site 1;
      postintervention documentation was significantly greater for Site 1 vs. Site 2
      (40% vs. 28%, P<0.01). CONCLUSIONS: We found an increase in documentation and
      management of overweight children following an EMR upgrade that calculates BMI
      percentiles for age and gender. Physician education was an important adjunct.

PMID- 21885431
TI  - Electrospray MS/MS reveals extensive and nonspecific oxidation of cholesterol
      esters in human peripheral vascular lesions.
AB  - Although LDL is rendered proatherogenic by various experimental treatments (e.g.,
      acetylation), the exact structural changes that drive LDL transformation in vivo
      remain enigmatic. Among the many hypothesized targets of oxidative modification
      are cholesterol esters (CE). This family of neutral lipids, which carries a
      highly unsaturated pool of fatty acyl groups, is the main component of both LDL
      particles and atherosclerotic plaques. Tandem mass spectrometry (MS/MS) was
      employed to reveal abundant and diverse oxidized CEs (oxCE), including novel
      oxidation products, within human peripheral vascular lesions. These oxCE species
      composed up to 40% of the total CE pool, with cholesteryl linoleate being
      oxidized to the greatest extent. Imaging mass spectrometry studies showed that
      oxCE was entirely confined within the plaque, along with unmodified CE and
      triacylglyceride (TAG). Interestingly, we found no evidence for TAG oxidation,
      although polyunsaturated species were abundant. Enzymatic oxidation of
      cholesteryl linoleate by 15-lipoxygenase (15-LO), an enzyme often invoked in CE
      oxidation, initially results in a regio- and stereospecific product. Analysis of
      intact cholesteryl hydroxyoctadecadienoate isomers in human atheromata revealed
      no regio- or stereospecificity, indicating 15-LO was either not a major source of
      oxCE or nonenzymatic processes had eroded any product specificity.

PMID- 21885434
TI  - The process of treating pediatric appendicitis.
AB  - BACKGROUND: A large service and distant geographical area can make the process of
      diagnosing and treating appendicitis a challenge. METHODS: Hospital records of
      children treated for appendicitis between 2007 and 2009 were retrospectively
      analyzed, including time from emergency (ER) to operating room (OR), diagnostic
      imaging (DI) utilization, preoperative antibiotic usage, operating time, length
      of stay (LOS), and perforation rate. RESULTS: The perforation rate was 34%, with
      longer LOS. Transfer time to the children's hospital between ER inside and
      outside the city was not different. ER to OR time was significantly shorter for
      patients assessed at the children's hospital directly. Ultrasound remained the
      most used DI modality (55%). Preoperative antibiotics were only fully
      administered in 42% of the cases. CONCLUSION: A clinical pathway for pediatric
      appendicitis may address the challenges of the process of pre-ER, ER to OR, and
      OR care to maintain an acceptable perforation rate.

PMID- 21885435
TI  - The association of intrapartum antibiotic exposure with the incidence and
      antibiotic resistance of infantile late-onset serious bacterial infections.
AB  - BACKGROUND: The widespread use of intrapartum antibiotics (IPA) has raised
      concerns regarding the adverse effects on the newborn. OBJECTIVES: To determine
      if IPA is associated with infantile late-onset serious bacterial infections
      (SBIs) and with antibiotic resistance. PATIENTS AND METHODS: From 2005 to 2009,
      data were prospectively collected for all infants born at our center, aged 7 to
      90 days, who were hospitalized for fever. Cases included infants with culture
      proven SBIs, and controls included infants without SBIs. Results. A total of 71
      cases and 124 controls were included. IPA was documented in 11.3% of cases and in
      7.3% of controls (P = .34). Among cases, ampicillin resistance was documented in
      85% of antibiotic-exposed infants and in 63% of nonexposed infants (P = .19).
      Corresponding rates for first-generation cephalosporin resistance in urinary
      tract infection were 75% and 23.5% (P = .04). CONCLUSION: IPA is associated with
      a trend toward increased antibiotic resistance in late-onset SBIs. This should be
      taken into consideration in the selection of empirical therapy for febrile
      infants.

PMID- 21885436
TI  - Vitamin C degradation products and pathways in the human lens.
AB  - Vitamin C and its degradation products participate in chemical modifications of
      proteins in vivo through non-enzymatic glycation (Maillard reaction) and
      formation of different products called advanced glycation end products. Vitamin C
      levels are particularly high in selected tissues, such as lens, brain and adrenal
      gland, and its degradation products can inflict substantial protein damage via
      formation of advanced glycation end products. However, the pathways of in vivo
      vitamin C degradation are poorly understood. Here we have determined the levels
      of vitamin C oxidation and degradation products dehydroascorbic acid, 2,3
      diketogulonic acid, 3-deoxythreosone, xylosone, and threosone in the human lens
      using o-phenylenediamine to trap both free and protein-bound adducts. In the
      protein-free fraction and water-soluble proteins (WSP), all five listed
      degradation products were identified. Dehydroascorbic acid, 2,3-diketogulonic
      acid, and 3-deoxythreosone were the major products in the protein-free fraction,
      whereas in the WSP, 3-deoxythreosone was the most abundant measured dicarbonyl.
      In addition, 3-deoxythreosone in WSP showed positive linear correlation with age
      (p < 0.05). In water-insoluble proteins, only 3-deoxythreosone and threosone were
      detected, whereby the level of 3-deoxythreosone was ~20 times higher than the
      level of threosone. The identification of 3-deoxythreosone as the major
      degradation product bound to human lens proteins provides in vivo evidence for
      the non-oxidative pathway of dehydroascorbate degradation into erythrulose as a
      major pathway for vitamin C degradation in vivo.

PMID- 21885437
TI  - ABIN1 protein cooperates with TAX1BP1 and A20 proteins to inhibit antiviral
      signaling.
AB  - Upon virus infection, the innate immune response provides the first line of
      protection and rapidly induces type I interferons (IFNalpha/beta), which mediate
      potent antiviral effects. To maintain homeostasis and prevent autoimmunity, IFN
      production is tightly regulated; however, the mechanisms of negative regulation
      are poorly understood. Herein, we demonstrate that the A20 binding inhibitor of
      NF-kappaB 1 (ABIN1) is a novel negative regulator of antiviral signaling.
      Overexpression of ABIN1 inhibited IFN-beta promoter activation in response to
      virus infection or poly(I:C) transfection, whereas siRNA-mediated knockdown of
      ABIN1 enhanced IFN-beta production upon virus infection. ABIN1 interacted with
      the A20 regulatory molecule TAX1BP1 and was essential for the recruitment of
      TAX1BP1 and A20 to the noncanonical IkappaB kinases TBK1 and IKKi in response to
      poly(I:C) transfection. ABIN1 and TAX1BP1 together disrupted the interactions
      between the E3 ubiquitin ligase TRAF3 and TBK1/IKKi to attenuate lysine 63-linked
      polyubiquitination of TBK1/IKKi. Finally, an intact ubiquitin binding domain of
      ABIN1 was essential for ABIN1 to interact with TBK1/IKKi and inhibit IFN-beta
      production upon poly(I:C) transfection or virus infection. Together, these
      results suggest that ABIN1 requires its ubiquitin binding domain and cooperates
      with TAX1BP1 and A20 to restrict antiviral signaling.

PMID- 21885438
TI  - Localization of ubiquinone-8 in the Na+-pumping NADH:quinone oxidoreductase from
      Vibrio cholerae.
AB  - Na(+) is the second major coupling ion at membranes after protons, and many
      pathogenic bacteria use the sodium-motive force to their advantage. A prominent
      example is Vibrio cholerae, which relies on the Na(+)-pumping NADH:quinone
      oxidoreductase (Na(+)-NQR) as the first complex in its respiratory chain. The
      Na(+)-NQR is a multisubunit, membrane-embedded NADH dehydrogenase that oxidizes
      NADH and reduces quinone to quinol. Existing models describing redox-driven Na(+)
      translocation by the Na(+)-NQR are based on the assumption that the pump contains
      four flavins and one FeS cluster. Here we show that the large, peripheral NqrA
      subunit of the Na(+)-NQR binds one molecule of ubiquinone-8. Investigations of
      the dynamic interaction of NqrA with quinones by surface plasmon resonance and
      saturation transfer difference NMR reveal a high affinity, which is determined by
      the methoxy groups at the C-2 and C-3 positions of the quinone headgroup. Using
      photoactivatable quinone derivatives, it is demonstrated that ubiquinone-8 bound
      to NqrA occupies a functional site. A novel scheme of electron transfer in Na(+)
      NQR is proposed that is initiated by NADH oxidation on subunit NqrF and leads to
      quinol formation on subunit NqrA.

PMID- 21885439
TI  - Lung tumor-associated osteoblast-derived bone morphogenetic protein-2 increased
      epithelial-to-mesenchymal transition of cancer by Runx2/Snail signaling pathway.
AB  - Bone is a frequent target of lung cancer metastasis and is associated with
      significant morbidity and a dismal prognosis. Interaction between cancer cells
      and the bone microenvironment causes a vicious cycle of tumor progression and
      bone destruction. This study analyzed the soluble factors secreted by lung tumor
      associated osteoblast (TAOB), which are responsible for increasing cancer
      progression. The addition of bone morphogenetic protein-2 (BMP-2), present in
      large amounts in TAOB conditioned medium (TAOB-CM) and lung cancer patient sera,
      mimicked the inductive effect of TAOB-CM on lung cancer migration, invasion, and
      epithelial-to-mesenchymal transition. In contrast, inhibition of BMP by noggin
      decreases the inductive properties of TAOB-CM and lung cancer patient sera on
      cancer progression. Induction of lung cancer migration by BMP-2 is associated
      with increased ERK and p38 activation and the up-regulation of Runx2 and Snail.
      Blocking ERK and p38 by a specific inhibitor significantly decreases cancer cell
      migration by inhibiting Runx2 up-regulation and subsequently attenuating the
      expression of Snail. Enhancement of Runx2 facilitates Rux2 to recruit p300, which
      in turn enhances histone acetylation, increases Snail expression, and decreases E
      cadherin. Furthermore, inhibiting Runx2 by siRNA also suppresses BMP-2-induced
      Snail up-regulation and cell migration. Our findings provide novel evidence that
      inhibition of BMP-2 or BMP-2-mediated MAPK/Runx2/Snail signaling is an attractive
      therapeutic target for osteolytic bone metastases in lung cancer patients.

PMID- 21885441
TI  - 2Bs or not 2Bs: that is the question.

PMID- 21885440
TI  - Oligomerization and pore formation by equinatoxin II inhibit endocytosis and lead
      to plasma membrane reorganization.
AB  - Pore-forming toxins have evolved to induce membrane injury by formation of pores
      in the target cell that alter ion homeostasis and lead to cell death. Many pore
      forming toxins use cholesterol, sphingolipids, or other raft components as
      receptors. However, the role of plasma membrane organization for toxin action is
      not well understood. In this study, we have investigated cellular dynamics during
      the attack of equinatoxin II, a pore-forming toxin from the sea anemone Actinia
      equina, by combining time lapse three-dimensional live cell imaging, fluorescence
      recovery after photobleaching, FRET, and fluorescence cross-correlation
      spectroscopy. Our results show that membrane binding by equinatoxin II is
      accompanied by extensive plasma membrane reorganization into microscopic domains
      that resemble coalesced lipid rafts. Pore formation by the toxin induces Ca(2+)
      entry into the cytosol, which is accompanied by hydrolysis of
      phosphatidylinositol 4,5-bisphosphate, plasma membrane blebbing, actin
      cytoskeleton reorganization, and inhibition of endocytosis. We propose that
      plasma membrane reorganization into stabilized raft domains is part of the
      killing strategy of equinatoxin II.

PMID- 21885443
TI  - GluA4 sustains sensing of sounds through stable, speedy, sumptuous, spineless
      synapses.

PMID- 21885442
TI  - Don't curse the darkness, light a candle: fluorescence studies of axon
      excitability.

PMID- 21885444
TI  - Diet and nerves: the impact of maternal feeding on newborn intestinal
      permeability.

PMID- 21885446
TI  - Molecular mechanisms underlying neurovascular protection in stroke.

PMID- 21885447
TI  - New perspectives on the theory of justice: implications for physical therapy
      ethics and clinical practice.
AB  - Recent revisions of physical therapy codes of ethics have included a new emphasis
      concerning health inequities and social injustice. This emphasis reflects the
      growing evidence regarding the importance of social determinants of health,
      epidemiological trends for health service delivery, and the enhanced
      participation of physical therapists in shaping health care reform in a number of
      international contexts. This perspective article suggests that there is a
      "disconnect" between the societal obligations and aspirations expressed in the
      revised codes and the individualist ethical frameworks that predominantly
      underpin them. Primary health care is an approach to health care arising from an
      understanding of the nexus between health and social disadvantage that considers
      the health needs of patients as expressive of the health needs of the communities
      of which they are members. It is proposed that re-thinking ethical frameworks
      expressed in codes of ethics can both inform and underpin practical strategies
      for working in primary health care. This perspective article provides a new focus
      on the ethical principle of justice: the ethical principle that arguably remains
      the least consensually understood and developed in the ethics literature of
      physical therapy. A relatively recent theory of justice known as the "capability
      approach to justice" is discussed, along with its potential to assist physical
      therapy practitioners to further develop moral agency in order to address
      situations of health inequity and social injustice in clinical practice.

PMID- 21885448
TI  - Moral agency as enacted justice: a clinical and ethical decision-making framework
      for responding to health inequities and social injustice.
AB  - This is the second of 2 companion articles in this issue. The first article
      explored the clinical and ethical implications of new emphases in physical
      therapy codes of conduct reflecting the growing evidence regarding the importance
      of social determinants of health, epidemiological trends for health service
      delivery, and the enhanced participation of physical therapists in shaping health
      care reform in a number of international contexts. The first article was
      theoretically oriented and proposed that a re-thinking of ethical frameworks
      expressed in codes of ethics could both inform and underpin practical strategies
      for working in primary health care. A review of the ethical principle of
      "justice," which, arguably, remains the least consensually understood and
      developed principle in the ethics literature of physical therapy, was provided,
      and a more recent perspective-the capability approach to justice-was discussed.
      The current article proposes a clinical and ethical decision-making framework,
      the ethical reasoning bridge (ER bridge), which can be used to assist physical
      therapy practitioners to: (1) understand and implement the capability approach to
      justice at a clinical level; (2) reflect on and evaluate both the fairness and
      influence of beliefs, perspectives, and context affecting health and disability
      through a process of "wide reflective equilibrium" and assist patients to do this
      as well; and (3) nurture the development of moral agency, in partnership with
      patients, through a transformative learning process manifest in a mutual
      "crossing" and "re-crossing" of the ER bridge. It is proposed that the
      development and exercise of moral agency represent an enacted justice that is the
      result of a shared reasoning and learning experience on the part of both
      therapists and patients.

PMID- 21885450
TI  - In tribute: Steve Haley.

PMID- 21885449
TI  - Impact of elliptical trainer ergonomic modifications on perceptions of safety,
      comfort, workout, and usability for people with physical disabilities and chronic
      conditions.
AB  - BACKGROUND: The popularity of elliptical training has grown in rehabilitation,
      fitness, and home settings as a means for improving fitness and walking, yet many
      people with physical disabilities and chronic conditions experience difficulties
      when trying to use elliptical trainers. OBJECTIVE: The purpose of this study was
      to compare, for people with disabilities and chronic conditions, perceptions of
      safety, comfort, workout, and usability of 4 elliptical trainers before and after
      the development of a set of low-cost adaptations. DESIGN: This study was a quasi
      experimental repeated-measures investigation. METHODS: Twenty adults with diverse
      medical conditions and functional abilities evaluated 4 elliptical trainers for
      safety, comfort, workout, and usability. Barriers to the use of the elliptical
      trainers and solutions to improve the use of the trainers were identified.
      Prototype modifications were designed, and participants reassessed the same
      features after the modifications were made. RESULTS: An integrated system (steps,
      bench, side rails, center rail or handle, deeper foot wells, and 1-handed heart
      rate monitor) was developed. Although at least 25% of participants required
      physical assistance to get on or off the elliptical trainers before modification,
      only one required this after modification. Before modification, only 1
      participant was able to mount each device independently; after modification, 6 to
      8 participants were able to do so. Up to 25% of participants continued to require
      assistance to initiate or sustain pedal movement. Compared with participants'
      ratings of the elliptical trainers before modification, those after modification
      were higher for safety (55% increase in visual analog scale ratings), comfort
      (43% higher), ability to achieve a good workout (23% greater), and usability (24%
      increase). LIMITATIONS: To date, only 4 elliptical trainers have been studied
      with a small sample of convenience. CONCLUSIONS: Elliptical trainers posed access
      challenges to people with disabilities, chronic conditions, or both.
      Implementation of low-cost modifications successfully reduced barriers and the
      need for assistance, enabling greater access for people who could benefit from
      using the devices for functional training and fitness.

PMID- 21885451
TI  - On "An obese body mass increases the adverse effects..." Bauer LO, Wu Z, Wolfson
      LI. Phys Ther. 2011;91:1063-1071.

PMID- 21885452
TI  - A multiparametric approach to monitor the effects of gamma-secretase inhibition
      along the whole intestinal tract.
AB  - gamma-secretase inhibitors (GSIs) have been recently proposed as chemopreventive
      agents in gastrointestinal neoplasia, because they lead, through inhibition of
      the Notch signaling pathway, to goblet cell conversion in some intestinal
      adenomas of the Apc(Min) mice, and halt epithelial cell proliferation. In this
      study, we examine in depth, in normal mice, the effects of a GSI, dibenzazepine
      (DBZ), intraperitoneally administered for 8 days at a non toxic dose, on the gene
      expression pattern of secretory mucin (MUC), goblet cell conversion, organization
      of the crypt structural-proliferative units, stem cell niche and apoptotic
      compartments, along the entire length of the small intestine and colon. We
      demonstrate that DBZ elicits a homogeneous goblet cell conversion all along the
      mouse intestinal tract, associated with an overexpression of the gene Muc2
      without ectopic expression of the gastric genes Muc5ac and Muc6, and with the
      emergence of lysozyme-positive 'intermediate cells' in the colon. Furthermore,
      DBZ treatment induces a heterogeneous reorganization of the crypt structural
      proliferative units along the intestinal tract and of the stem cell niche in the
      colon, without disturbing the apoptotic compartment. These findings point to
      uncoupled effects of a GSI on goblet cell conversion and reorganization of the
      intestinal crypt structural-proliferative units and stem cell niche, and suggest
      caution in the use of GSIs as chemopreventive agents for intestinal neoplasia.

PMID- 21885453
TI  - Effects of systematic oral care in critically ill patients: a multicenter study.
AB  - BACKGROUND: No standard oral assessment tools are available for determining
      frequency of oral care in critical care patients, and the method of providing
      oral care is controversial. OBJECTIVES: To examine the effects of a systematic
      program of oral care on oral assessment scores in critically ill intubated and
      nonintubated, patients. METHODS: Clinical data were collected 3 times during
      critical care admissions before and after institution of a systematic program of
      oral care in 3 different medical centers. The oral care education program
      consisted of instruction from a dentist or dental hygienist and a clear procedure
      outlining systematic oral care. The Beck Oral Assessment Scale and the mucosal
      plaque score were used to assess the oral cavity. Data were analyzed by using
      linear mixed modeling with controls for severity of illness. RESULTS: Scores on
      the Beck Scale differed significantly (F = 4.79, P = .01) in the pattern of
      scores across the 3 days and between the control group (before oral education)
      and the systematic oral care group. Unlike the control group, the treatment group
      had decreasing scores on the Beck Scale from day 1 to day 5. The mucosal-plaque
      score and the Beck Scale scores had strong correlations throughout the study; the
      highest correlation was on day 5 (r = 0.798, P < .001, n = 43). CONCLUSIONS: Oral
      assessment scores improved after nurses implemented a protocol for systematic
      oral care. Use of the Beck Scale and the mucosal-plaque score could standardize
      oral assessment and guide nurses in providing oral interventions.

PMID- 21885454
TI  - Hypoglycemic events in intensive care patients: analysis by insulin
      administration method and sample type.
AB  - BACKGROUND: Intensive insulin treatment is associated with an increased risk of
      hypoglycemia, so strict glycemic monitoring is essential. The best type of sample
      for identifying hypoglycemia remains under debate. OBJECTIVES: To establish the
      number of hypoglycemic events in intensive care patients relative to insulin
      administration method and the method used to collect the blood sample. METHODS:
      Retrospective descriptive study lasting 6 months. Hypoglycemia was defined as a
      blood glucose level less than 80 mg/dL (mild: 50-79 mg/dL, severe: <50 mg/dL),
      measured with a bedside glucometer and blood from the arterial catheter or
      fingerstick, in critically ill patients who require insulin administered
      subcutaneously (with sliding scales) or via continuous intravenous perfusion
      (intense infusion protocol with a nurse-managed insulin therapy algorithm).
      RESULTS: Analysis of the 6636 samples from 144 critically ill patients revealed
      188 mildly hypoglycemic samples (2.8%) and 3 severely hypoglycemic samples
      (0.04%). The prevalence of mild hypoglycemia was greater when insulin was
      administered intravenously (3.2%) rather than subcutaneously (2.3%; P = .04).
      Among patients receiving insulin intravenously, hypoglycemia was found more often
      in arterial (4.5%) than in capillary (2.8%) blood (P = .01). The prevalence of
      hypoglycemia in capillary blood samples did not differ significantly between
      subcutaneous (2.3%) and intravenous (2.8%) insulin therapies (P = .21).
      CONCLUSIONS: With a target blood glucose level of 110 to 140 mg/dL, few
      hypoglycemic events are detected in critically ill patients, regardless of
      whether insulin is administered intravenously or subcutaneously. Analysis of
      solely arterial samples may yield a higher prevalence of hypoglycemia than
      otherwise.

PMID- 21885455
TI  - September 2011: a time to remember and prepare.

PMID- 21885457
TI  - Predictors of pressure ulcers in adult critical care patients.
AB  - BACKGROUND: Pressure ulcers are one of the most underrated conditions in
      critically ill patients. Despite the introduction of clinical practice guidelines
      and advances in medical technology, the prevalence of pressure ulcers in
      hospitalized patients continues to escalate. Currently, consensus is lacking on
      the most important risk factors for pressure ulcers in critically ill patients,
      and no risk assessment scale exclusively for pressure ulcers in these patients is
      available. OBJECTIVE: To determine which risk factors are most predictive of
      pressure ulcers in adult critical care patients. Risk factors investigated
      included total score on the Braden Scale, mobility, activity, sensory perception,
      moisture, friction/shear, nutrition, age, blood pressure, length of stay in the
      intensive care unit, score on the Acute Physiology and Chronic Health Evaluation
      II, vasopressor administration, and comorbid conditions. METHODS: A
      retrospective, correlational design was used to examine 347 patients admitted to
      a medical-surgical intensive care unit from October 2008 through May 2009.
      RESULTS: According to direct logistic regression analyses, age, length of stay,
      mobility, friction/shear, norepinephrine infusion, and cardiovascular disease
      explained a major part of the variance in pressure ulcers. CONCLUSION: Current
      risk assessment scales for development of pressure ulcers may not include risk
      factors common in critically ill adults. Development of a risk assessment model
      for pressure ulcers in these patients is warranted and could be the foundation
      for development of a risk assessment tool.

PMID- 21885458
TI  - Pressure ulcer prevention.

PMID- 21885459
TI  - Patient-related factors associated with hospital discharge to a care facility
      after critical illness.
AB  - BACKGROUND: Many critically ill patients are transferred to other care facilities
      instead of to home at hospital discharge. OBJECTIVE: To identify patient-related
      factors associated with hospital discharge to a care facility after critical
      illness and to estimate the magnitude of risk associated with each factor.
      METHODS: Retrospective cohort study of 548 survivors of critical illness in a
      medical intensive care unit. Multivariable logistic regression was used to
      identify independent risk factors for discharge to a care facility. Only the
      first 72 hours of intensive care were analyzed. RESULTS: Approximately one
      quarter of the survivors of critical illness were discharged to a care facility
      instead of to home. This event occurred more commonly in older patients, even
      after adjustment for severity of illness and comorbid conditions (odds ratio [OR]
      1.8 for patients >= 65 years of age vs patients < 65 years; 95% confidence
      interval [CI], 1.1-3.1; P = .02). The risk was greatest for patients who received
      mechanical ventilation (OR, 3.4; 95% CI, 2.0-5.8; P < .001) or had
      hospitalizations characterized by severe cognitive dysfunction (OR, 8.1; 95% CI,
      1.3-50.6; P = .02) or poor strength and/or mobility (OR, 31.7; 95% CI, 6.4-157.3;
      P < .001). The model showed good discrimination (area under the curve, 0.82; 95%
      CI, 0.77-0.86). CONCLUSION: The model, which did not include baseline function or
      social variables, provided good discrimination between patients discharged to a
      care facility after critical illness and patients discharged to home. These
      results suggest that future research should focus on the debilitating effects of
      respiratory failure and on conditions with cognitive and neuromuscular sequelae.

PMID- 21885460
TI  - Measurement of end-tidal carbon dioxide in spontaneously breathing children after
      cardiac surgery.
AB  - BACKGROUND: Respiratory monitoring is important after surgery to prevent
      pulmonary complications. End-tidal carbon dioxide (Petco(2)) measurement by
      capnometry is an indirect and noninvasive measurement of Pco(2) in blood and is
      accepted and recognized in critical care. OBJECTIVES: To determine the
      correlation and level of agreement between Petco(2) and Paco(2) in spontaneously
      breathing children after cardiac surgery and to determine whether Petco(2)
      measured by using tidal volume (Vt-Petco(2)) or vital capacity (VC-Petco(2))
      shows more or less significant correlation with Paco(2). METHODS: Vt-Petco(2) and
      VC-Petco(2) by capnometry and Paco(2) by blood gas analysis were measured once a
      day after tracheal extubation. The determination coefficient and degree of bias
      between the methods were assessed in children with and without supplemental
      oxygen. RESULTS: A total of 172 Vt-Petco(2), VC-Petco(2), and Paco(2) values from
      48 children were analyzed. The overall coefficients of determination were 0.84 (P
      < .001) for Vt-Petco(2) and Paco(2) and 0.62 (P = .02) for VC-Petco(2) and
      Paco(2). The mean gradient for Paco(2) to Petco(2) in all groups increased with
      the increase in supplemental oxygen; the gradient was significantly larger in the
      groups given 2 to 5 L of oxygen per minute. CONCLUSIONS: In spontaneously
      breathing children, Vt-Petco(2) provided a more accurate estimate of Paco(2) than
      did VC-Petco(2), especially in children given little or no supplemental oxygen.
      The difference between the methods was significantly larger in the groups given 2
      to 5 L of oxygen per minute.

PMID- 21885461
TI  - Factors associated with the level of backrest elevation in a thoracic
      cardiovascular intensive care unit.
AB  - BACKGROUND: Ventilator-associated pneumonia is a complication of mechanical
      ventilation that is associated with increased length of stay, morbidity,
      mortality, and costs. Evidence-based guidelines to reduce the risk of ventilator
      associated pneumonia recommend use of 30o to 45o backrest elevation. Despite
      recommendations, patients continue to be cared for in positions with a lower
      backrest elevation. Hemodynamic stability may be a factor in the lack of
      adherence, yet few data exist to confirm this hypothesis. OBJECTIVE: To determine
      the relationship between backrest elevation and hemodynamic instability among
      patients in a thoracic cardiovascular intensive care unit. METHODS: A sample of
      100 patients was studied. Patients were randomly selected by time of day. A
      protractor was used to measure patients' backrest elevation. Mean blood pressure,
      time of day, and fluid and vasopressor use also were recorded. RESULTS: Lower
      backrest elevation was associated with use of vasopressors (P = .001). Patients
      who received hemodynamic support also had a lower backrest elevation than did
      patients not receiving these therapies (mean, 19o vs 26o ; P = .01). Patients
      with a mean blood pressure of 64 mm Hg or less had a mean backrest elevation of
      17o versus 24o for patients with a mean blood pressure greater than 65 mm Hg (P =
      .01). Back-rest elevations did not differ between shifts. CONCLUSION: That
      backrest elevation is associated with lower mean blood pressure and vasopressor
      use suggests that nurses are not adhering to recommended levels of backrest
      elevation so as to maintain hemodynamic stability. Further studies are needed to
      elucidate reasons for lack of adherence to recommended levels of backrest
      elevation.

PMID- 21885462
TI  - Coronary artery dominance.

PMID- 21885463
TI  - Levels of neutrophil gelatinase-associated lipocalin in 2 patients with crush
      syndrome after a mudslide.
AB  - Neutrophil gelatinase-associated lipocalin is one of the most promising
      biomarkers for the diagnosis of acute kidney injury. An increase in the level of
      neutrophil gelatinase-associated lipocalin is a good predictor of acute kidney
      injury and is associated with an increase in the serum level of creatinine. Two
      victims of a mudslide in Messina, Italy, initially had crush syndrome followed by
      development of acute kidney injury. The development of acute kidney injury is the
      second most common cause of death after large earthquakes and other natural
      disasters, but at the same time, crush-related acute kidney injury is one of the
      few life-threatening complications of crush injuries that can be reversed if
      diagnosed early and treated. In this case, measuring the level of neutrophil
      gelatinase-associated lipocalin enabled early diagnosis of acute kidney injury
      and anticipation of the changes in levels of conventional markers such as
      creatinine.

PMID- 21885464
TI  - NEW EAE/ASE recommendations for the use of echocardiography in new transcatheter
      interventions for valvular heart disease.
AB  - The new full and detailed recommendations later in this issue are summarized here
      by Jose L. Zamorano, MD, FESC, chair EAE writing group.

PMID- 21885465
TI  - EAE/ASE recommendations for the use of echocardiography in new transcatheter
      interventions for valvular heart disease.
AB  - The introduction of devices for transcatheter aortic valve implantation, mitral
      repair, and closure of prosthetic paravalvular leaks has led to a greatly
      expanded armamentarium of catheter-based approaches to patients with regurgitant
      as well as stenotic valvular disease. Echocardiography plays an essential role in
      identifying patients suitable for these interventions and in providing intra
      procedural monitoring. Moreover, echocardiography is the primary modality for
      post-procedure follow-up. The echocardiographic assessment of patients undergoing
      transcatheter interventions places demands on echocardiographers that differ from
      those of the routine evaluation of patients with native or prosthetic valvular
      disease. Consequently, the European Association of Echocardiography in
      partnership with the American Society of Echocardiography has developed the
      recommendations for the use of echocardiography in new transcatheter
      interventions for valvular heart disease. It is intended that this document will
      serve as a reference for echocardiographers participating in any or all stages of
      new transcatheter treatments for patients with valvular heart disease.

PMID- 21885466
TI  - Association of body composition and left ventricular dimensions in elite
      athletes.
AB  - BACKGROUND: Correction for body composition is recommended for appropriate
      interpretation of equivocally altered cardiac dimensions. We sought to
      investigate the impact of body composition on athletes' heart. METHODS: Left
      ventricular mass (LVM), septal wall thickness (SWT) and end-diastolic diameter
      (LVEDD) were measured by echocardiography in 1051 elite athletes (26% female,
      aged 18-40 years) and in 338 sedentary controls matched for age, gender and body
      size. Body fat was determined by skinfold thickness measurements. RESULTS:
      Normative ranges are provided for LVM, LVEDD and SWT scaled to body surface area
      (BSA), height, height(2.7) and fat-free mass (FFM). The strongest correlation was
      found for FFM (r = 0.70; 0.64; 0.49; p < 0.001 each). LVM, LVEDD and SWT differed
      significantly (p < 0.05) between athletes of low, moderate and high dynamic
      disciplines. Correcting LVEDD for height(2.7) eliminated these differences (p >
      0.05), whereas LVM and SWT remained significantly increased in high dynamic
      athletes despite correction for body size. Gender differences were consistently
      eliminated by scaling LVEDD to FFM(0.33) and SWT to BSA, but scaled LVM remained
      significantly increased in male athletes. Compared to sedentary controls,
      significant differences in LVEDD and SWT disappeared after correction for
      height(2.7) and FFM, but LVM again remained significantly higher in athletes.
      CONCLUSIONS: Adaptation of left ventricular dimensions to exercise training is
      closely related to body composition, in particular to FFM. The normative ranges
      for LVEDD, SWT and LVM scaled to body size aid interpretation of equivocal
      alterations in elite athletes. However, the increase of LVM in particular reveals
      exercise-induced adaptations beyond these associations.

PMID- 21885468
TI  - Testing the construct validity of the gambling functional assessment-revised.
AB  - An attempt was made to modify the Gambling Functional Assessment (GFA), which was
      proposed to identify four possible contingencies maintaining the respondent's
      gambling behavior. However, previous research found that it only identified two
      contingencies (i.e., positive vs. negative reinforcement), with some items cross
      loading on both contingencies and one not loading at all. A total of 1,060
      undergraduate students completed a revised version of the GFA containing 22
      items. Exploratory factor analyses conducted on a random selection of half of the
      participants led to a two-factor solution (positive and negative reinforcement)
      for 16 of the items that strongly loaded on the two factors. Confirmatory factor
      analyses conducted using structural equation modeling on the data from the other
      half of the sample confirmed the two-factor model. The GFA-Revised consists of 16
      items, 8 each measuring positive and negative reinforcement contingencies.
      Although this revised measure cleanly parses the two contingencies, the data
      indicate that gambling maintained by positive reinforcement is more frequent than
      gambling maintained by negative reinforcement. This outcome will make directly
      comparing the two contingencies difficult, especially given that evidence
      suggests that gambling maintained by negative reinforcement is more strongly
      associated with pathology than gambling maintained by positive reinforcement.

PMID- 21885469
TI  - Should nonsuicidal self-injury be a putative obsessive-compulsive-related
      condition? A critical appraisal.
AB  - Nonsuicidal self-injury (NSSI) has many behavioral and cognitive features that
      would make it appear to be closely tied to obsessive-compulsive disorder (OCD).
      Obsessive-compulsive-related disorders (OCRDs) have been described in the
      literature as conditions that share a common phenomenology, neurobiology, and
      treatment response. The authors reviewed the literature describing the degree
      that NSSI is similar to, and distinct from, OCRDs based on these hypothesized
      common areas. They conclude with recommendations for conceptualization that draws
      partly from the OCRD literature and from cognitive-behavioral models of
      rumination.

PMID- 21885470
TI  - Adherence to treatment in a behavioral intervention curriculum for parents of
      children with autism spectrum disorder.
AB  - Parents (N = 21) of children with autism spectrum disorders responded to a survey
      on adherence to skills instruction and problem behavior management strategies
      they had previously been observed to master in a standardized training curriculum
      based on the principles of applied behavior analysis. Survey items were guided by
      existing models of and research in treatment adherence. Parents reported
      adherence below observed mastery criteria in five of six skill areas. Three
      independent variables indexing caregiver perception were significantly correlated
      with reported adherence: perceived effectiveness as a behavior change agent,
      confidence in the intervention to produce meaningful change, and acceptance of
      child in family and community. Perceived confidence significantly predicted
      adherence in a regression model (p < .05). Implications of caregiver perception
      in explanatory frameworks for adherence are discussed, and next steps in the
      measurement and study of treatment adherence in behavior analysis are proposed.

PMID- 21885467
TI  - Deciphering the genetic basis of animal domestication.
AB  - Genomic technologies for livestock and companion animal species have
      revolutionized the study of animal domestication, allowing an increasingly
      detailed description of the genetic changes accompanying domestication and breed
      development. This review describes important recent results derived from the
      application of population and quantitative genetic approaches to the study of
      genetic changes in the major domesticated species. These include findings of
      regions of the genome that show between-breed differentiation, evidence of
      selective sweeps within individual genomes and signatures of demographic events.
      Particular attention is focused on the study of the genetics of behavioural
      traits and the implications for domestication. Despite the operation of severe
      bottlenecks, high levels of inbreeding and intensive selection during the history
      of domestication, most domestic animal species are genetically diverse. Possible
      explanations for this phenomenon are discussed. The major insights from the
      surveyed studies are highlighted and directions for future study are suggested.

PMID- 21885471
TI  - Labelled antibody-based one-step time-resolved fluoroimmunoassay for measurement
      of free thyroxine in serum.
AB  - BACKGROUND: Valid assays measuring free thyroxine (FT4) must perform without bias
      despite large variations in the concentrations and affinities of serum thyroxine
      binding proteins in the population. We developed a new, rapid one-step labelled
      antibody time-resolved fluoroimmunoassay (TRFIA) for FT4. METHODS: Based on the
      heterologous combination of anti-T4 monoclonal antibody and triiodothyronine
      immunoglobulin G conjugate, a one-step TRFIA for FT4 detection was established
      and compared with the two-step DELFIA((r)) Free Thyroxine Assay. Matrix
      interference caused by endogenous binders and exogenous non-esterified fatty
      acids (NEFA) was also accessed in the proposed assay. RESULTS: The developed
      method generally took only one hour, had a detection limit of 0.6 pmol/L and a
      large linear range of 2.5-120 pmol/L. The inter- and intra-assay coefficients of
      variation were 3.5-6.6% and 4.4-9.8%, respectively. Results from 110 specimens
      showed apparent agreement with that from the DELFIA((r)) FT4 Assay with the
      square of the correlation coefficient of 0.975. This assay indicated that there
      was no significant dependence on endogenous binders and displayed potential
      interference by exogenous NEFA up to 5 mmol/L. CONCLUSIONS: The proposed one-step
      heterologous TRFIA FT4 assay possesses simplicity, accuracy, high sensitivity and
      exhibits great potential for FT4 measurement. The combination of heterologous
      immunoassay with TRFIA may be advantageous for FT4 immunoassay development.

PMID- 21885472
TI  - Screening for drugs of abuse: which matrix, oral fluid or urine?
AB  - Urine is recognized as the prime matrix for drug test screening with well
      established methods and testing protocols. Its major limitation is with regard to
      the inconvenience of sample collection and lack of integrity due to adulteration,
      dilution, drug spiking or sample exchange. The question is whether oral fluid,
      with its apparent better sample integrity, can replace urine for drug screening.
      This review examines the sample integrity problems and the advantages and
      limitations of oral fluid and urine in drug screening programmes. The variety of
      sample collection devices for oral fluid is shown to be a problem with recovery
      and detection for some drugs. This is examined in relation to the
      pharmacokinetics of drug metabolism and excretion in this matrix. Buccal
      contamination with drugs in oral fluid may also cause problems with
      interpretation. The clinical advantages of oral fluid analysis compared with
      urine testing are highlighted. Parent drugs are often found in oral fluid where
      only their metabolites may be found in urine, for example the benzodiazepines. 6
      Monoacetylmorphine, an indicative marker of heroin, has a high prevalence in oral
      fluid from users of this drug but its detection in urine is limited due to its
      short half-life. Advances in analytical techniques, particularly chromatography
      linked to tandem mass spectrometry, are helping to promote oral fluid analysis.
      However, the lack of concordance studies examining both urine and oral fluid drug
      levels and kinetics in the clinical setting is of some concern.

PMID- 21885473
TI  - A national audit of estimated glomerular filtration rate and proteinuria
      reporting in the UK.
AB  - BACKGROUND: Within the UK there has been a rapid move to include the reporting of
      estimated glomerular filtration rate (eGFR) values to identify patients with
      chronic kidney disease (CKD). Guidance has also changed since its original
      introduction. This national audit aimed to establish how eGFR is reported by
      laboratories within the UK. METHODS: A questionnaire was sent to 164 UK National
      Health Service laboratories, which included questions on the patient groups who
      had eGFR reported, the eGFR thresholds used, adjustments made for ethnicity and
      the means of identifying proteinuria. The audit standards used were based on the
      2008 National Institute for Health and Clinical Excellencec (NICE) CKD guidance.
      RESULTS: One hundred and thirty-one of the 164 laboratories (80%) responded.
      Forty-six percent reported eGFR on all adult requests while 36% limited use to
      general practitioners. Twenty-one percent did not issue eGFR to any inpatient.
      Sixty-two percent and 30% of laboratories had an upper reporting limit of >=90
      and >=60 mL/min/1.73 m(2), respectively; the remainder having higher thresholds.
      Sixty percent cited an ethnicity 'correction factor' on the report, 59% in a
      guideline but 28% in neither. An albumin:creatinine ratio was used by 63% to
      detect non-diabetic proteinuria, while 37% exclusively used a protein:creatinine
      ratio. CONCLUSIONS: There has been rapid implementation of eGFR reporting in the
      UK since 2006. However, there is considerable variation in the way it is
      reported, with few laboratories currently exactly matching existing NICE
      recommendations. A reassessment of biochemical CKD assessment by most
      laboratories following a reiteration and clarification of current recommendations
      seems warranted.

PMID- 21885474
TI  - Endovascular repair of the half aortic arch in pigs with an improved, single
      branched stent graft system for the brachiocephalic trunk.
AB  - The objective of this study was to evaluate the feasibility of endovascular
      repair of half of the aortic arch in pigs using an improved, integrated, single
      branched stent graft for the ascending aorta and brachiocephalic trunk (BCT). We
      designed an improved stent graft in an integrated fashion and deployed the stent
      grafts into the ascending aortas and BCT of eight pigs. The feasibility of the
      stent graft deployments was evaluated three months after the procedures using
      arteriography, computed tomography angiography (CTA) and animal autopsy. The
      stent grafts were successfully deployed in eight pigs. All animals survived for
      at least three months. Arteriography, CTA and animal necropsy revealed good stent
      fixation in eight cases. Their head CT scans found no evidence of cerebral
      infarction. In conclusion, endovascular repair of the half aortic arch with the
      integrated single-branched stent graft system appears to be safe and feasible in
      pigs.

PMID- 21885475
TI  - A rare case of giant popliteal artery aneurysm in a young adult.
AB  - Popliteal artery aneurysms (PAAs) are rare in the general population, but are the
      most common peripheral aneurysms. PAAs are often bilateral and are associated
      with abdominal aortic aneurysms. They usually affect older men with established
      cardiovascular disease caused by atherosclerosis. Whenever they occur in younger
      men, other more unusual etiologies such as trauma, mycotic aneurysm, inflammatory
      arteritis or popliteal entrapment are responsible. The authors report a rare case
      of giant congenital PAA, revealed by acute limb ischemia in a 23-year-old
      patient. The evolution after resection of the popliteal aneurysm and end-to-end
      anastomosis with synthetic graft was favorable.

PMID- 21885476
TI  - Pyoderma gangrenosum: a new complication after groin exposure for attempted
      endovascular aortic stent-graft placement.
AB  - Pyoderma gangrenosum (PG) is an uncommon and frequently misdiagnosed inflammatory
      dermatosis. This neutrophilic inflammation of the dermis has been well described
      in relation to other inflammatory illnesses (i.e. inflammatory bowel disease).
      Although rare, PG is increasingly described in relation to trauma or surgical
      interventions. It is important for vascular surgeons to be aware of the potential
      development of PG at vascular access sites. Although endovascular surgery is a
      minimally invasive form of vascular surgery, it does require cutaneous
      manipulation, which can incite PG. The purpose of this report is to describe a
      case of PG that developed after an attempted endovascular surgery and to
      elucidate this rare dermatologic disorder's diagnosis and treatment.

PMID- 21885477
TI  - A role for the putative cannabinoid receptor GPR55 in the islets of Langerhans.
AB  - The cannabinoid CB1 receptor is a well-known player in energy homeostasis and its
      specific antagonism has been used in clinical practice for the treatment of
      obesity. The G protein-coupled receptor GPR55 has been recently proposed as a new
      cannabinoid receptor and, by contrast, its pharmacology is still enigmatic and
      its physiological role is largely unexplored, with no reports investigating its
      putative role in metabolism. Thus, we aim to investigate in rats the presence,
      distribution and putative physiological role of GPR55 in a key metabolic tissue,
      the endocrine pancreas. We found high Gpr55 mRNA content in pancreatic islets and
      considerable protein distribution in insulin-secreting beta-cells. Activation of
      GPR55 by the agonist O-1602 increased calcium transients (P<0.01) and insulin
      secretion (P<0.001) stimulated by glucose. This latter effect was blunted in
      Gpr55 KO mice suggesting that O-1602 is acting, at least in part, through GPR55.
      Indeed, acute in vivo experiments showed that GPR55 activation increases glucose
      tolerance (P<0.05) and plasma insulin levels (P<0.05), suggesting an in vivo
      physiological relevance of GPR55 systemic stimulation. Taken together, these
      results reveal the expression of GPR55 receptors in the endocrine pancreas as
      well as its function at stimulus-secretion coupling of insulin secretion,
      suggesting a role in glucose homeostasis. In this context, it may also represent
      a new target for consideration in the management of type 2 diabetes and related
      diseases.

PMID- 21885478
TI  - Inflammatory effects of patagonfibrase, a metalloproteinase from Philodryas
      patagoniensis (Patagonia Green Racer; Dipsadidae) venom.
AB  - Patagonfibrase is a P-III class metalloproteinase isolated from the venom of
      Philodryas patagoniensis, a South-American, rear-fanged 'colubrid' snake
      responsible for accidents with clinical significance. Since local inflammatory
      reactions are conspicuous signs of snakebites inflicted by this species and
      taking into consideration that most snake venom metalloproteinases exhibit
      inflammatory activity, this study deals with the proinflammatory effects evoked
      by patagonfibrase. Herein, we demonstrate that patagonfibrase causes a time- and
      dose-dependent hemorrhagic edema when injected into mouse hind paws. The peak of
      edema occurred at 30 min after injection, and the minimum edematogenic dose was
      0.021 MUg. By histological analysis, the presence of moderate to marked edema and
      hemorrhage, and a mild inflammatory infiltrate was observed. When injected
      subcutaneously into the scrotal bag of mice, patagonfibrase induced cell
      recruitment with a significant alteration in physiological parameters of
      leukocyte-endothelium interaction. The presence of 1 mmol/L o-phenanthroline,
      which chelates metal ions, significantly inhibited the proinflammatory effects
      induced by patagonfibrase. Taken together, these results imply that
      patagonfibrase is an important contributor to local inflammation elicited by P.
      patagoniensis envenomation, which may pave the way for novel therapeutic
      strategies to treat this snakebite. Moreover, our findings demonstrate for the
      first time that a venom metalloproteinase from a rear-fanged snake elicits
      proinflammatory effects mainly mediated by its catalytic activity.

PMID- 21885479
TI  - The emerging roles of fatty acid translocase/CD36 and the aryl hydrocarbon
      receptor in fatty liver disease.
AB  - The fatty acid translocase (FAT)/CD36 belongs to the class B scavenger receptor
      family. In addition to the known functions of CD36 in the uptake of oxidized low
      density lipoprotein by macrophages and uptake of fatty acids by adipose tissues,
      skeletal muscle and heart, emerging evidence has pointed to an equally important
      function of CD36 in the uptake of fatty acids in the liver and the pathogenesis
      of fatty liver disease. Recent reports have also suggested CD36 as a shared
      transcriptional target of several ligand-sensing and lipogenic transcriptional
      factors, such as the aryl hydrocarbon receptor, and several nuclear hormone
      receptors, such as pregnane X receptor, liver X receptor and peroxisome
      proliferator activated receptor gamma. Non-alcoholic fatty liver disease is
      common and medically significant, because it is closely related to metabolic
      syndrome and has a potential to progress into the more harmful non-alcoholic
      steatohepatitis. It is hoped that CD36 and their transcriptional regulators can
      represent novel therapeutic targets for the prevention and management of fatty
      liver disease.

PMID- 21885480
TI  - Lentivirus-mediated expression of cDNA and shRNA slows degeneration in retinitis
      pigmentosa.
AB  - Mutations in Pde6b lead to high levels of signaling molecules cyclic guanosine
      monophosphate (cGMP) and Ca(2+), which ultimately result in photoreceptor cell
      death in certain forms of retinitis pigmentosa (RP). The level of cGMP, which is
      controlled by opposing activities of guanylate cyclase (GUCY) and photoreceptor
      phosphodiesterase-6 (PDE6), regulates the opening of cyclic nucleotide-gated ion
      channels [CNG] and thereby controls Ca(2+) influx into the outer segments. Using
      a lentiviral gene therapy approach, we have previously shown that degeneration
      can be temporarily slowed either by introducing wild-type PDE6beta or knocking
      down expression of GUCY2E and CNGA1 in photoreceptors of Pde6b(H620Q), a mouse
      model for RP. Rescue was transient with either approach. Therefore, we tested a
      novel combination therapy using bipartite lentiviral vectors designed to both
      introduce wild-type PDE6beta expression and knockdown GUCY2E or CNGA1. Immunoblot
      analysis shows simultaneous increases in PDE6beta and decreases in GUCY2E or
      CNGA1 in retinas transduced by the vectors, indicating successful transduction.
      In Pde6b(H620Q) mutants, we observe rescue of photoreceptor function and an
      increase in photoreceptor rows as compared with untreated controls. However, no
      evidence of prolonged rescue beyond the limit of the previously tested single
      therapy was observed.

PMID- 21885481
TI  - A unique homologue of the eukaryotic protein-modifier ubiquitin present in the
      bacterium Bacteroides fragilis, a predominant resident of the human
      gastrointestinal tract.
AB  - In the complete genome sequences of Bacteroides fragilis NCTC9343 and 638R, we
      have discovered a gene, ubb, the product of which has 63 % identity to human
      ubiquitin and cross-reacts with antibodies raised against bovine ubiquitin. The
      sequence of ubb is closest in identity (76 %) to the ubiquitin gene from a
      migratory grasshopper entomopoxvirus, suggesting acquisition by inter-kingdom
      horizontal gene transfer. We have screened clinical isolates of B. fragilis from
      diverse geographical regions and found that ubb is present in some, but not all,
      strains. The gene is transcribed and the mRNA is translated in B. fragilis, but
      deletion of ubb did not have a detrimental effect on growth. BfUbb has a
      predicted signal sequence; both full-length and processed forms were detected in
      whole-cell extracts, while the processed form was found in concentrated culture
      supernatants. Purified recombinant BfUbb inhibited in vitro ubiquitination and
      was able to covalently bind the human E1 activating enzyme, suggesting it could
      act as a suicide substrate in vivo. B. fragilis is one of the predominant members
      of the normal human gastrointestinal microbiota with estimates of up to >1011
      cells per g faeces by culture. These data indicate that the gastro-intestinal
      tract of some individuals could contain a significant amount of aberrant
      ubiquitin with the potential to inappropriately activate the host immune system
      and/or interfere with eukaryotic ubiquitin activity. This discovery could have
      profound implications in relation to our understanding of human diseases such as
      inflammatory bowel and autoimmune diseases.

PMID- 21885483
TI  - Serum hepcidin: a direct link between anemia of inflammation and coronary artery
      atherosclerosis in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To investigate the role of hepcidin as an inducer of anemia of
      inflammation in patients with rheumatoid arthritis (RA), and its correlation to
      coronary artery atherosclerosis. METHODS: Our study included 60 patients with RA
      and 20 healthy controls. Anemic RA patients with serum transferrin receptors/log
      ferritin (sTfR-F) index value < 1.5 were classified as having pure anemia of
      chronic disease (ACD), and patients with sTfR-F index value > 1.5 were classified
      as having anemia of chronic disease with coexistent iron deficiency anemia
      (ACD+IDA). Measurements were taken for Disease Activity Score for 28 joints
      (DAS28), Modified Health Assessment Questionnaire (MHAQ), erythrocyte
      sedimentation rate (ESR), high sensitivity C-reactive protein (hsCRP), rheumatoid
      factor (RF), lipid profile, serum interleukin 6 (IL-6), tumor necrosis factor
      alpha, iron studies, and serum hepcidin. Coronary calcium score (CCS) was
      measured using multislice spiral computed tomography as a marker of
      atherosclerosis. RESULTS: Serum hepcidin was found to be higher in anemic
      patients with RA than in controls (p < 0.001), and higher in the pure ACD
      subgroup than in the ACD+IDA subgroup (p < 0.001). Hepcidin concentration was
      positively correlated with disease duration, ESR, hsCRP, RF, DAS28, MHAQ, serum
      ferritin, IL-6, and mean CCS and inversely correlated with hemoglobin, sTfR, and
      the sTfR-F index. CONCLUSION: Hepcidin can be considered a key inducer of anemia
      of inflammation in patients with RA. This inflammation was proved to be directly
      linked to coronary artery atherosclerosis. The correlations between serum
      hepcidin with disease activity and IL-6 raise the possibility of using it as a
      surrogate marker for disease activity.

PMID- 21885482
TI  - Role of sialidase in glycoprotein utilization by Tannerella forsythia.
AB  - The major bacterial pathogens associated with periodontitis include Tannerella
      forsythia. We previously discovered that sialic acid stimulates biofilm growth of
      T. forsythia, and that sialidase activity is key to utilization of sialoconjugate
      sugars and is involved in host-pathogen interactions in vitro. The aim of this
      work was to assess the influence of the NanH sialidase on initial biofilm
      adhesion and growth in experiments where the only source of sialic acid was
      sialoglycoproteins or human oral secretions. After showing that T. forsythia can
      utilize sialoglycoproteins for biofilm growth, we showed that growth and initial
      adhesion with sialylated mucin and fetuin were inhibited two- to threefold by the
      sialidase inhibitor oseltamivir. A similar reduction (three- to fourfold) was
      observed with a nanH mutant compared with the wild-type. Importantly, these data
      were replicated using clinically relevant serum and saliva samples as substrates.
      In addition, the ability of the nanH mutant to form biofilms on glycoprotein
      coated surfaces could be restored by the addition of purified NanH, which we show
      is able to cleave sialic acid from the model glycoprotein fetuin and, much less
      efficiently, 9-O-acetylated bovine submaxillary mucin. These data show for the
      first time that glycoprotein-associated sialic acid is likely to be a key in vivo
      nutrient source for T. forsythia when growing in a biofilm, and suggest that
      sialidase inhibitors might be useful adjuncts in periodontal therapy.

PMID- 21885484
TI  - The association of LRP5 gene polymorphisms with ankylosing spondylitis in a
      Chinese Han population.
AB  - OBJECTIVE: To clarify the association between polymorphisms of low-density
      lipoprotein receptor-related protein 5 (LRP5) with ankylosing spondylitis (AS) in
      a Chinese Han population. METHODS: Sixteen patients with AS were recruited for
      preliminary screening through gene sequencing. Then 14 single-nucleotide
      polymorphisms (SNP) of LRP5 were followed up in 296 patients and 170 controls.
      RESULTS: Sequencing the LRP5 showed 24 SNP including 3 novel SNP [LRP5SNP1 (c.
      1596T > C), LRP5SNP2 (c.3764-30G > A), and LRP5SNP3 (c.4488+74G > A)]. Validation
      of SNP showed that the LRP5SNP3 were associated with AS after multiple testing
      correction (allele P(c) = 0.0087, genotype P(c) = 0.0316, haplotype AGA, P(c) =
      0.0051, OR = 2.54 and haplotype AGG, P(c) = 0.048, OR = 0.63, respectively). The
      SNP rs686921 was associated with male predominance in both patients with AS (p =
      0.032, OR 1.54) and controls (p = 0.014, OR 1.94). CONCLUSION: LRP5 may be
      involved in the pathogenesis of AS. Further study will be required to clarify the
      effect of LRP5 on the pathogenic mechanism of AS.

PMID- 21885485
TI  - Early management of newly diagnosed rheumatoid arthritis by Canadian
      rheumatologists: a national, multicenter, retrospective cohort.
AB  - OBJECTIVE: To describe early rheumatologic management for newly diagnosed
      rheumatoid arthritis (RA) in Canada. METHODS: A retrospective cohort of 339
      randomly selected patients with RA diagnosed from 2001-2003 from 18 rheumatology
      practices was audited between 2005-2007. RESULTS: The most frequent initial
      disease-modifying antirheumatic drugs (DMARD) included hydroxychloroquine (55.5%)
      and methotrexate (40.1%). Initial therapy with multiple DMARD (15.6%) or single
      DMARD and corticosteroid combinations (30.7%) was infrequent. Formal assessment
      measures were noted infrequently, including the Health Assessment Questionnaire
      (34.6%) and Disease Activity Score for 28 joints (8.9%). CONCLUSION: Initial
      pharmacotherapy is consistent with guidelines from the period. The infrequent
      reporting of multiple DMARD combinations and formal assessment measures has
      implications for current clinical management and warrants contemporary
      reassessment.

PMID- 21885486
TI  - Association analysis of polymorphisms in lumican gene and systemic lupus
      erythematosus in a Taiwan Chinese Han population.
AB  - OBJECTIVE: Lumican (LUM) is predominantly localized in areas of pathological
      fibrosis. To determine whether polymorphisms in LUM gene are associated with
      development of systemic lupus erythematosus (SLE), we analyzed 2 single
      nucleotide polymorphisms (SNP) of LUM in a Taiwan Chinese Han population.
      METHODS: Participants included 168 patients with SLE and 192 age-matched controls
      in whom examinations had excluded SLE. Genotyping of -628 A/-(rs17018757) and
      c.1567 T/C polymorphisms in LUM were carried out in each patient and control
      using the polymerase chain reaction-restriction fragment-length polymorphism
      method, and validated by Taqman SNP genotyping assay. Data were correlated with
      the development of SLE and various clinical symptoms by chi-square analysis.
      RESULTS: Frequencies of C/C genotype and the C allele at c.1567 T/C were
      significantly higher in patients than controls. Polymorphism at c.1567 C/T was
      found to be associated with arthritis and photosensitivity in patients with SLE,
      which are both connective tissue-related symptoms. CONCLUSION: The c.1567 T/C
      polymorphism of LUM is related to the development and clinical symptoms of SLE.

PMID- 21885487
TI  - Effectiveness of a third tumor necrosis factor-alpha-blocking agent compared with
      rituximab after failure of 2 TNF-blocking agents in rheumatoid arthritis.
AB  - OBJECTIVE: To compare the effectiveness of a third tumor necrosis factor-alpha
      (TNF-alpha)-blocking agent with rituximab after failure of 2 TNF-blocking agents
      in patients with rheumatoid arthritis (RA) in daily clinical practice. METHODS:
      Patients receiving a third TNF-blocking agent or rituximab after failure of 2 TNF
      blocking agents were selected from a Dutch biologic registry. The primary outcome
      was the results from the Disease Activity Score of 28 joints (DAS28) over the
      first 12 months after start of the third biologic using mixed-model analyses.
      Secondary outcomes included the course of the Health Assessment Questionnaire
      (HAQ) and the separate components of the DAS28 over the first 12 months and the
      change from baseline in DAS28 and HAQ at 3 and 6 months. RESULTS: The overall
      course of the DAS28 over the first 12 months was significantly better for
      rituximab (p = 0.0044), as also observed for the HAQ, although the latter results
      were not statistically significant (p = 0.0537). The erythrocyte sedimentation
      rates, C-reactive protein, and swollen joint counts showed a better course for
      rituximab (p = 0.0008, p = 0.0287, p = 0.0547, respectively), but not the tender
      joint counts or visual analog scale for general health. DAS28 decreased
      significantly in both groups at 3 and 6 months (p <= 0.024), but the change in
      HAQ was significant for rituximab only at 3 months (p = 0.009). CONCLUSION:
      During the first 12 months of therapy, a larger improvement in disease activity
      and a trend toward a larger decrease in functional disability was observed in
      patients receiving rituximab. Switching to a biologic with another mechanism of
      action might be more effective after failure of 2 TNF-blocking agents in RA.

PMID- 21885488
TI  - Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50
      enhances the ability of SLE Responder Index to identify responders in clinical
      trials.
AB  - OBJECTIVE: To evaluate the performance of the Systemic Lupus Erythematosus (SLE)
      Responder Index (SRI) when the SLE Disease Activity Index 2000 (SLEDAI-2K) is
      substituted with SLEDAI-2K Responder Index-50 (SRI-50), a valid and reliable
      index of disease activity improvement. Also, to determine whether the SRI-50 will
      enhance the ability of SRI in detecting responders. METHODS: Our study was
      conducted on patients who attended the Lupus Clinic from September 2009 to
      September 2010. SLEDAI-2K, SRI-50, the British Isles Lupus Assessment Group
      measure, and the Physician's Global Assessment were determined initially and at
      followup. SRI was determined at the followup visit according to its original
      definition using the SLEDAI-2K score and by substituting SLEDAI-2K with SRI-50.
      RESULTS: A total of 117 patients with SLEDAI-2K >= 4 at baseline were studied.
      Patients had 1 followup visit over a 3-month period. Twenty-nine percent of
      patients met the original definition of SRI and 35% of patients met the
      definition of SRI when SLEDAI-2K was substituted with SRI-50. The use of SRI-50
      allowed determination of significant improvement in 7 additional patients. This
      improvement could not be discerned with the use of SLEDAI-2K as a component of
      SRI. At followup visits that showed improvement, SRI-50 scores decreased to a
      greater extent than SLEDAI-2K scores (p < 0.0001). CONCLUSION: SRI-50 enhances
      the ability of SRI to identify patients with clinically important improvement in
      disease activity. SRI-50 was superior to SLEDAI-2K in detecting partial clinical
      improvement, >= 50%, between visits. These properties of the SRI-50 enable it to
      be used as an independent outcome measure of improvement or as a component of SRI
      in clinical trials.

PMID- 21885489
TI  - Effect of Bosentan on systemic sclerosis-associated interstitial lung disease
      ineligible for cyclophosphamide therapy: a prospective open-label study.
AB  - OBJECTIVE: To evaluate the clinical benefits of the endothelin receptor
      antagonist bosentan on interstitial lung disease (ILD) in patients with systemic
      sclerosis (SSc) who are ineligible for cyclophosphamide (CYC) therapy. METHODS:
      In this prospective open-label study, 9 patients with SSc and ILD received
      bosentan for 24 months. The main reasons for avoiding CYC included severely
      impaired lung function, long disease duration, and relapse after CYC treatment.
      Pulmonary function tests and Doppler echocardiograms were evaluated every 6
      months, and high-resolution computed tomography (HRCT) was performed every 12
      months. For an extended survival analysis, 17 historical controls who met the
      inclusion criteria at referral and had not used any immunosuppressive or
      antifibrotic agents thereafter were selected from the SSc database. RESULTS: Two
      patients did not finish the study; one developed vasculitis requiring high-dose
      corticosteroids and another died of bacterial pneumonia. The remaining 7 patients
      tolerated bosentan and completed the study period. There were trends toward
      mildly reduced forced vital capacity, total lung capacity, and diffusing capacity
      for carbon monoxide over time. Two patients developed pulmonary hypertension
      during the 24-month period. HRCT scores for ground-glass opacity, pulmonary
      fibrosis, and honeycomb cysts gradually increased. In the extended study, there
      was no difference in cumulative survival rate between the bosentan-treated and
      historical control groups. CONCLUSION: The gradual worsening of pulmonary
      function and HRCT findings in patients treated with bosentan was consistent with
      the natural course of SSc-associated ILD. This study does not support the use of
      bosentan for SSc-associated ILD even when CYC treatment is inadvisable.

PMID- 21885490
TI  - Effects of bedtime very low dose cyclobenzaprine on symptoms and sleep physiology
      in patients with fibromyalgia syndrome: a double-blind randomized placebo
      controlled study.
AB  - OBJECTIVE: To determine the effects of bedtime very low dose (VLD)
      cyclobenzaprine (CBP) on symptoms and sleep physiology of patients with
      fibromyalgia (FM), unrefreshing sleep, and the alpha-nonREM sleep
      electroencephalographic (EEG) anomaly at screening. METHODS: Of 37 patients with
      FM in the screened population, 36 were randomized and treated in this 8-week,
      double-blind, placebo-controlled, dose-escalating study of VLD CBP 1-4 mg at
      bedtime. We evaluated changes in subjective symptoms including pain, tenderness,
      fatigue, mood [Hospital Anxiety and Depression Scale (HAD)], and objective EEG
      sleep physiology (at screening, baseline, and Weeks 2, 4, and 8). RESULTS: In the
      VLD CBP-treated group (n = 18) over 8 weeks, musculoskeletal pain and fatigue
      decreased, tenderness improved; total HAD score and the HAD depression subscore
      decreased; patient-rated and clinician-rated fatigue improved. In the placebo
      treated group (n = 18), none of these outcome measures changed significantly.
      Compared to placebo at 8 weeks, VLD CBP significantly improved pain, tenderness,
      and the HAD Depression subscore. Analysis of cyclic alternating pattern (CAP)
      sleep EEG revealed that significantly more subjects in the VLD CBP group than the
      placebo group had increased nights of restorative sleep in which
      CAP(A2+A3)/CAP(A1+A2+A3) = CAP(A2+A3(Norm)) <= 33%. For VLD CBP-treated subjects,
      the increase in nights with CAP(A2+A3(Norm)) <= 33% was correlated to
      improvements in fatigue, total HAD score, and HAD depression score. CONCLUSION:
      Bedtime VLD CBP treatment improved core FM symptoms. Nights with CAP(A2+A3(Norm))
      <= 33% may provide a biomarker for assessing treatment effects on nonrestorative
      sleep and associated fatigue and mood symptoms in persons with FM.

PMID- 21885491
TI  - Abatacept plus methotrexate provides incremental clinical benefits versus
      methotrexate alone in methotrexate-naive patients with early rheumatoid arthritis
      who achieve radiographic nonprogression.
AB  - OBJECTIVE: This article reports 1-year clinical outcomes in the subgroup of
      patients with rheumatoid arthritis in the Abatacept study to Gauge Remission and
      joint damage progression in methotrexate-naive patients with Early Erosive
      rheumatoid arthritis (AGREE) who achieved radiographic nonprogression at the end
      of the double-blind phase. METHODS: Patients who achieved radiographic
      nonprogression (change from baseline in total Sharp score <= 0 at 12 months) with
      abatacept plus methotrexate (MTX) or MTX alone were eligible for this analysis.
      Clinical outcomes were remission, defined by 28-joint Disease Activity Score
      (DAS28) using C-reactive protein (CRP), low Disease Activity Score (LDAS),
      American College of Rheumatology (ACR) scores, physical function (Health
      Assessment Questionnaire), and tender and swollen joint counts. Safety was
      assessed at each visit. RESULTS: Patients in the abatacept plus MTX and MTX
      monotherapy groups had similar baseline characteristics and were similar to the
      overall study population. The proportion of patients who achieved DAS28 (CRP)
      remission or LDAS was greater with abatacept plus MTX vs MTX alone [43.2% vs
      22.7% (p < 0.001) and 57.4% vs 40.6% (p = 0.008), respectively]. More patients
      receiving abatacept plus MTX achieved key ACR responses, including major clinical
      response (27.3% vs 11.9%; p < 0.001). Safety profiles were similar in both
      treatment groups. CONCLUSION: More MTX-naive patients with early RA who achieved
      radiographic nonprogression taking abatacept plus MTX also achieved DAS28 (CRP)
      defined remission and LDAS compared with patients who received MTX alone,
      supporting the use of abatacept as a first-line biologic in combination with
      disease-modifying antirheumatic drugs.

PMID- 21885492
TI  - FCRL3 -169C/C genotype is associated with anti-citrullinated protein antibody
      positive rheumatoid arthritis and with radiographic progression.
AB  - OBJECTIVE: Studies of Caucasian populations have shown conflicting results
      concerning the association between a promoter polymorphism -169T>C of the Fc
      receptor-like 3 (FCRL3) gene and rheumatoid arthritis (RA). It is unknown whether
      FCRL3 is associated with autoantibody status and disease severity. We
      investigated associations between FCRL3 -169T>C and autoantibody status and joint
      damage in patients with RA. METHODS: A total of 652 Norwegian patients with RA
      from 2 cohorts and 981 Norwegian controls, previously genotyped for FCRL3 -169T>C
      (rs7528684), were studied. Data on anticitrullinated protein antibodies (ACPA)
      and rheumatoid factor (RF) were available. The EURIDISS cohort (disease duration
      <= 4 yrs at baseline) was followed longitudinally, with assessment of
      radiographic hand damage at baseline and after 10 years (n = 117) according to
      the van der Heijde-modified Sharp score. RESULTS: We found significant
      associations with ACPA-positive RA for both the C allele (OR 1.28, 95% CI 1.08
      1.52, p = 0.004) and the C/C genotype (OR 1.57, 95% CI 1.18-2.10, p = 0.002).
      Similar associations were seen with RF-positive RA. No association was found with
      ACPA-negative or RF-negative RA. The C/C genotype was found to be associated with
      10-year radiographic progression in multivariate linear and logistic regression
      analyses, after adjustment for ACPA, erythrocyte sedimentation rate, age, and
      sex. CONCLUSION: The promoter polymorphism of FCRL3 was associated with
      autoantibody-positive RA. Despite the low number of patients, the C/C genotype of
      the FCRL3 polymorphism consistently and independently predicted radiographic
      progression. These findings suggest that FCRL3 is involved in both disease
      susceptibility and progression.

PMID- 21885494
TI  - Emerging issues in pharmacological management of rheumatoid arthritis: results of
      a national needs assessment survey identifying practice variations for the
      development of Canadian Rheumatology Association clinical practice
      recommendations.
AB  - OBJECTIVE: To describe Canadian clinical practice patterns in the pharmacological
      management of rheumatoid arthritis (RA) and identify practice variations.
      METHODS: A 44-item pre-guideline needs assessment survey was sent to all members
      of the Canadian Rheumatology Association (CRA). Descriptive statistics were used
      to summarize respondent characteristics and practice patterns. RESULTS: Survey
      respondents (n = 164) reported variations in practice regarding assessment
      strategies, treatment with disease-modifying antirheumatic drug monotherapy
      versus combination therapy, methotrexate dosing and escalation, corticosteroid
      strategies, and optimal use of biologics. CONCLUSIONS: Practice variations
      identified in this pre-guideline needs assessment survey were used to formulate
      key treatment questions for the development of CRA recommendations.

PMID- 21885493
TI  - Resistin levels in lupus and associations with disease-specific measures, insulin
      resistance, and coronary calcification.
AB  - OBJECTIVE: To evaluate levels of resistin in female subjects with systemic lupus
      erythematosus (SLE) compared to age and race-matched controls and to determine
      the relationship between resistin and systemic inflammation, disease measures,
      and coronary artery calcification (CAC). METHODS: Resistin levels were measured
      on stored samples from 159 women with SLE and 70 controls as an extension of a
      previous cross-sectional study. Spearman correlations and multivariable
      regressions were used to examine whether resistin levels were associated with
      SLE, disease-specific and inflammatory markers, insulin resistance, and CAC.
      RESULTS: In a multivariable linear regression model, a diagnosis of SLE was
      significantly associated with higher resistin levels independent of age, race,
      renal function, body mass index (BMI), high-sensitivity CRP (hsCRP),
      hypertension, diabetes, and steroid use. In SLE, resistin levels correlated
      positively with Systemic Lupus International Collaborating Clinics Damage Index,
      glomerular filtration rate (GFR), hsCRP, erythrocyte sedimentation rate,
      homocysteine, and disease duration (all p < 0.03). Resistin level did not
      correlate with markers of insulin resistance or body adiposity, including
      homeostatic model assessment or BMI. Resistin levels were significantly elevated
      in SLE cases with CAC compared to cases without CAC (16.58 vs 13.10 ng/ml,
      respectively; p = 0.04). In multivariate logistic regression, the association was
      not present after adjustment for age, race, and GFR. CONCLUSION: SLE was
      independently associated with higher resistin levels. Among subjects with SLE,
      higher resistin level correlated positively with renal dysfunction, inflammatory
      markers, and disease damage but not with insulin resistance or BMI. SLE cases
      with CAC had higher resistin levels than cases without CAC; however, this
      relationship was dependent on other established risk factors.

PMID- 21885495
TI  - Undertreatment of disease activity in systemic lupus erythematosus patients with
      endstage renal failure is associated with increased all-cause mortality.
AB  - OBJECTIVE: In a cohort of systemic lupus erythematosus (SLE) patients with
      endstage renal failure, to evaluate whether continuing rheumatology followup
      visits and immunosuppressive therapy after starting renal replacement were
      associated with increased survival. METHODS: We identified all SLE patients over
      21 years old who started renal replacement therapy between 2005 and 2011 at an
      urban tertiary care center. Mortality data were obtained using in-hospital
      records and the US Social Security Death Index database. RESULTS: We identified
      80 SLE patients undergoing renal replacement therapy. Twenty-two patients (28%)
      were followed in rheumatology clinics frequently (2 or more visits per year)
      after starting renal replacement therapy, and 58 patients (72%) were followed
      infrequently (fewer than 2 visits per year). Survival rates were significantly
      higher in transplant patients compared with dialysis patients. Patients with SLE
      followed frequently after starting dialysis had significantly higher 4-year
      survival rates compared with patients followed infrequently after starting
      dialysis (log-rank p = 0.03). In the Cox proportional hazards model, treatment
      with prednisone alone or with no medication was associated with a hazard ratio
      (HR) of death = 6.1 (95% CI 1.1, 34; p = 0.04) and HR = 13 (95% CI 1.5, 106; p =
      0.02), respectively, compared with patients treated with a combination of
      immunosuppressive therapy with or without prednisone, adjusted for age at SLE
      diagnosis, sex, transplant status, and the frequency of rheumatology visits after
      the development of endstage renal failure. CONCLUSION: Active disease in patients
      with SLE undergoing renal replacement therapy may be underrecognized and
      undertreated, leading to increased mortality.

PMID- 21885496
TI  - Relation of HLA-B27, tumor necrosis factor-alpha promoter gene polymorphisms, and
      T cell cytokine production in ankylosing spondylitis -- a comprehensive genotype
      phenotype analysis from an observational cohort.
AB  - OBJECTIVE: In a pilot study, a distinct T cell cytokine pattern associated with
      HLA-B27 status and a tumor necrosis factor-alpha (TNF-alpha) promoter gene
      polymorphism was found at -308 (TNF-308). The objective of our study was to
      assess these associations in a different cohort of patients with ankylosing
      spondylitis (AS) and to evaluate any effect on clinical measurements. METHODS:
      Peripheral T cell cytokine production of patients with AS (n = 121) from the
      German Spondyloarthritis Inception Cohort was assessed by flow cytometry and
      correlated with HLA-B27, TNF-238, and TNF-308, and with clinical measurements.
      RESULTS: In HLA-B27-positive, anti-TNF-naive patients with AS, the percentages of
      TNF-alpha-producing (5.02%) and interleukin 10-producing (0.31%) CD8+ cells were
      significantly lower in comparison to HLA-B27-negative patients (9.52%, p = 0.048,
      and 0.46%, p = 0.037, respectively). A nonsignificant trend was found for a lower
      production of TNF-alpha by CD4+ and interferon-gamma by both CD4+ and CD8+ T
      cells, as compared to HLA-B27-negative patients with AS (p > 0.05 for all
      comparisons). The A allele at TNF-308 was associated with a lower percentage of
      TNF-alpha-producing CD4+ T cells. No significant correlations were found between
      clinical or radiological measurements and cytokine production or with TNF-alpha
      promoter gene polymorphisms. CONCLUSION: Modulation of T cell cytokines by HLA
      B27 might play a role in AS pathogenesis in B27-positive individuals. No
      conclusive data were obtained for the TNF-308 polymorphism on cytokine
      production, and no effect of cytokines or genetic polymorphisms on clinical
      manifestations was observed.

PMID- 21885497
TI  - High risk of ischemic heart disease in patients with lupus nephritis.
AB  - OBJECTIVE: To investigate the occurrence of ischemic heart disease (IHD) in a
      cohort of 104 Danish patients with biopsy-proven lupus nephritis (LN). METHODS:
      Information on all hospitalizations in Denmark for IHD between 1977 and 2006 was
      obtained from the Danish National Hospital Register. Occurrence of IHD after date
      of first renal biopsy in the LN cohort was compared to the occurrence of IHD in
      the general population by calculation of standardized ratios of observed to
      expected events (O:E ratios) for different manifestations of IHD registered
      during inpatient and outpatient hospital visits. RESULTS: The median duration of
      followup was 14.7 (range 0.1-30.0) years. Thirty-one first-time hospitalizations
      for IHD occurred in the cohort, yielding an overall O:E ratio for IHD of 6.8 (95%
      CI 4.6-9.7). Increased risks were found for angina pectoris (O:E ratio 6.0, 95%
      CI 3.0-11), myocardial infarction (O:E ratio 7.9, 95% CI 3.8-15), and other IHD
      related diagnoses combined (O:E ratio 6.9, 95% CI 3.3-13). A high IHD risk was
      observed for patients aged < 31 years at time of first renal biopsy (O:E ratio
      17.1, 95% CI 9.1-29) and for patients aged 30-39 years during followup (O:E ratio
      42.3, 95% CI 21-76). Patients undergoing chronic renal replacement therapy also
      had a pronounced risk of IHD (O:E ratio 19.4, 95% CI 7.8-40). CONCLUSION: LN is
      associated with markedly increased morbidity from IHD. Our findings indicate that
      patients with early-onset LN have a disturbingly high risk of IHD compared to the
      general population.

PMID- 21885498
TI  - Minimally important difference of Health Assessment Questionnaire in psoriatic
      arthritis: relating thresholds of improvement in functional ability to patient
      rated importance and satisfaction.
AB  - OBJECTIVE: To evaluate changes in function as measured by Health Assessment
      Questionnaire Disability Index (HAQ-DI) and the meaningfulness of the changes, in
      importance and satisfaction, in patients with psoriatic arthritis (PsA). METHODS:
      HAQ-DI was assessed at baseline and at Weeks 4, 12, and 24 in a randomized double
      blind study of 205 patients with active PsA receiving etanercept 25 mg twice
      weekly or placebo. Concurrently, patients rated the importance of and
      satisfaction with their change in function on a 7-point scale (1 = not at all
      important/satisfied; 7 = extremely important/satisfied). Mean HAQ-DI improvement
      corresponding to ratings of minimally (2-3) or very (6-7) important or satisfied
      was determined using a posthoc linear mixed-model analysis. Patient importance
      ratings were used as an anchor to estimate minimally important difference (MID)
      for HAQ-DI; distribution-based estimates were also calculated. RESULTS: A total
      of 161 patients (69 placebo; 92 etanercept) had >= 1 HAQ-DI scores showing
      improvement from baseline and a corresponding importance or satisfaction rating.
      HAQ-DI improvements corresponding to importance scale ratings of 2 or 3 were
      0.335 (95% CI 0.214, 0.455) and 0.360 (95% CI 0.263, 0.456), respectively,
      suggesting an MID of about 0.35. HAQ-DI improvements corresponding to
      satisfaction scale ratings of 2 and 3 were 0.293 (95% CI 0.230, 0.357) and 0.360
      (95% CI 0.307, 0.413). For a given change in HAQ-DI, nearly two-thirds of
      patients indicated a lower rating for satisfaction than for importance. This
      trial was registered in the ClinicalTrials.gov registry (NCT00317499).
      CONCLUSION: Our study suggests the MID for HAQ-DI in PsA is about 0.35. The
      results may also provide insight into patient satisfaction with changes in
      function and expectations for therapy.

PMID- 21885499
TI  - Adalimumab or cyclosporine as monotherapy and in combination in severe psoriatic
      arthritis: results from a prospective 12-month nonrandomized unblinded clinical
      trial.
AB  - OBJECTIVE: To assess the efficacy and safety of adalimumab or cyclosporine (CYC)
      as monotherapy or combination therapy for patients with active psoriatic
      arthritis (PsA), despite methotrexate (MTX) therapy. METHODS: A prospective 12
      month, nonrandomized, unblinded clinical trial of 57, 58, and 55 patients who
      received CYC (2.5-3.75 mg/kg/day), adalimumab (40 mg every other week), or
      combination, respectively. Lowering of concomitant nonsteroidal antiinflammatory
      drugs (NSAID) and corticosteroids and reductions of adalimumab and/or CYC doses
      in responding patients were not restricted. RESULTS: Mean numbers of
      tender/swollen joints at baseline were 9.7/6.7 in CYC-treated, 13.0/7.8 in
      adalimumab-treated, and 14.5/9.4 in combination-treated patients, indicating
      lesser disease severity of patients assigned to the first group. The Psoriatic
      Arthritis Response Criteria at 12 months were met by 65% of CYC-treated (p =
      0.0003 in favor of combination treatment), 85% of adalimumab-treated (p = 0.15 vs
      combination treatment), and 95% of combination-treated patients, while the
      American College of Rheumatology-50 response rates were 36%, 69%, and 87%,
      respectively (p < 0.0001 and p = 0.03 in favor of combination treatment). A
      significantly greater mean improvement in Health Assessment Questionnaire
      Disability Index was achieved by combination treatment (-1.11) vs CYC (-0.41) or
      adalimumab alone (-0.85). Combination therapy significantly improved Psoriasis
      Area and Severity Index-50 response rates beyond adalimumab, but not beyond the
      effect of CYC monotherapy. Doses of NSAID and corticosteroids were reduced in
      combination-treated patients; CYC doses and frequency of adalimumab injections
      were also reduced in 51% and 10% of them, respectively. No new safety signals
      were observed. CONCLUSION: The combination of adalimumab and CYC is safe and
      seemed to produce major improvement in both clinical and serological variables in
      patients with severely active PsA and inadequate response to MTX.

PMID- 21885500
TI  - Levels of serum matrix metalloproteinase-3 correlate with disease activity in the
      enthesitis-related arthritis category of juvenile idiopathic arthritis.
AB  - OBJECTIVE: Serum matrix metalloproteinase-3 (MMP-3) has been shown to reflect
      disease activity in ankylosing spondylitis (AS) and rheumatoid arthritis.
      Elevated levels have been found in juvenile idiopathic arthritis (JIA). In the
      enthesitis-related arthritis category of JIA (JIA-ERA), we studied whether serum
      MMP-3 levels and ratios of MMP-3/tissue inhibitor of metalloproteinase (TIMP-1)
      are correlated with disease activity and whether they are sensitive to change in
      disease activity. METHODS: A total of 54 patients with JIA-ERA (International
      League of Associations for Rheumatology criteria) were enrolled for study.
      Baseline disease activity measures included tender and swollen joint counts,
      Maastricht AS Enthesitis Score, Bath AS Disease Activity Index (BASDAI), Bath AS
      Functional Index (BASFI), patient assessment of pain and global disease activity,
      physician assessment of global disease activity, and erythrocyte sedimentation
      rate (ESR). Serum MMP-3 and TIMP-1 levels were measured using ELISA. A group of
      24 patients were followed up for longitudinal study. RESULTS: The mean age of 54
      patients (48 males) at disease onset was 11.8 +/- 4.19 years and duration of
      disease was 5.2 +/- 4.3 years. Median ESR was 65 mm/h (range 46.5-97) and median
      BASDAI was 3.4 (range 2.5-4.7). Median MMP-3, TIMP-1, and MMP-3/TIMP-1 ratio were
      50.4 ng/ml (IQR 13.0-193.8), 228.9 ng/ml (IQR 108.2-290.4), and 0.3 (IQR 0.07
      1.13), respectively. At inclusion MMP-3 levels correlated directly with various
      disease activity measures: tender joint count (TJC; r = 0.60), swollen joint
      count (SJC; r = 0.45), BASFI (r = 0.29), BASDAI (r = 0.32), ESR (r = 0.49),
      physician global assessment (r = 0.40), patient visual analog scale for pain (r =
      0.28), and patient global assessment (r = 0.38; all p < 0.05). MMP-3/TIMP-1 ratio
      correlated only with TJC (r = 0.51), SJC (r = 0.39), and ESR (r = 0.34; p <
      0.05). At followup, change in MMP-3 correlated with changes in TJC (r = 0.42) and
      SJC (r = 0.44; p < 0.05), while change in ESR did not correlate with change in
      any disease activity measure. CONCLUSION: MMP-3 levels are a good marker for
      disease activity in JIA-ERA.

PMID- 21885501
TI  - Decoy receptor 3 attenuates collagen-induced arthritis by modulating T cell
      activation and B cell expansion.
AB  - OBJECTIVE: To investigate the immune-modulated effects of decoy receptor 3 (DCR3)
      in an experimental model of rheumatoid arthritis (RA). METHODS: We delivered DCR3
      plasmid into collagen-induced arthritis (CIA) mice using the hydrodynamic method
      and evaluated the serum level of DCR3 protein by ELISA. After immunization, we
      assessed disease severity of arthritis incidence, arthritis scores, paw
      thickness, and means of arthritic limbs, and used hematoxylin and eosin staining
      to observe synovial hyperplasia. We analyzed numbers of murine splenocytes and
      inguinal lymphocyte cells, cell populations, and serum proinflammatory cytokines
      by flow cytometry. We investigated B cell proliferation by carboxyfluorescein
      succinimidyl ester assay. We evaluated serum levels of total IgG2a and type II
      collagen-specific IgG and IgG2a using ELISA. RESULTS: DCR3 expression in sera
      significantly attenuated disease severity in CIA mice. We found that DCR3
      inhibited the volume of inguinal lymph nodes, numbers of CD19+ B cells, and
      populations of interferon-gamma, interleukin 4 (IL-4), IL-17A, and Foxp3
      producing CD4+ T cell in vivo. We found that DCR3 inhibited Pam3CSK4 (Toll-like
      receptor 1/2 ligand)-induced B220+ B cell proliferation in vitro. DCR3 treatment
      reduced the serum level of IL-6, total IgG2a, and CII-specific IgG2a antibody.
      CONCLUSION: We postulated that the protective effects of DCR3 in CIA resulted
      from modulation of the immune system by maintaining the B/T cell balance and
      decreasing lymphocyte expansion. We suggest DCR3 as a prophylactic and potential
      therapeutic agent in the treatment of RA.

PMID- 21885502
TI  - Defining the mechanism of action of herbal therapies in rheumatoid arthritis: is
      this the road to clinical development and acceptance?

PMID- 21885503
TI  - Inclusion criteria based on DAS28 score: strength of improvement is less
      dependent on baseline disease activity than expected.

PMID- 21885504
TI  - Generic versus disease-specific measures of health-related quality of life in
      systemic lupus erythematosus.

PMID- 21885505
TI  - The Salpetriere Hospital in Paris and its role in the beginnings of modern
      rheumatology.

PMID- 21885506
TI  - Eosinophilic granuloma of the middle ear.

PMID- 21885507
TI  - Cryptogenic organizing pneumonia mimicking malignancy in a patient with
      rheumatoid arthritis.

PMID- 21885508
TI  - OMERACT 10 Sharp Symposium: important findings in examination of imaging methods
      for measurement of joint damage in rheumatoid arthritis.
AB  - The Sharp Symposium was held at the Outcome Measures in Rheumatology Clinical
      Trials 2010 meeting (OMERACT 10) in honor of the late John Sharp, consummate
      rheumatologist and researcher. The symposium focused on the status of current
      scoring methods in radiography, magnetic resonance imaging (MRI), and ultrasound
      (US) in rheumatoid arthritis (RA), as well as on the use of soluble and tissue
      biomarkers in RA, with the aim of updating recommendations regarding methods for
      enhanced detection, monitoring, and prediction of joint damage in clinical
      trials.

PMID- 21885509
TI  - Patterns of magnetic resonance imaging bone erosion in rheumatoid arthritis-
      which bones are most frequently involved and show the most change?
AB  - OBJECTIVE: To investigate by magnetic resonance imaging (MRI) which bones in
      wrists and metacarpophalangeal (MCP) joints most frequently show bone erosions,
      and which most frequently demonstrate erosive progression, in early and
      established rheumatoid arthritis (RA). METHODS: MRI datasets from 258 RA patients
      [126 with early RA (disease duration < 6 months)] were analyzed, of whom 223,
      including 126 with early RA, had 1-year followup MRI. All patients had MRI of one
      wrist, whereas 86 patients had additional images of 2nd-5th MCP joints, and 46
      patients additional images of the contralateral wrist. MRI were evaluated blinded
      by one reader, according to the OMERACT RA MRI scoring system (RAMRIS) for
      erosions, and presence/absence of erosions was noted in each bone, as was
      presence/absence of erosive progression. RESULTS: The capitate, ulna, lunate,
      triquetrum, and scaphoid were the 5 bones with both most frequent baseline
      erosions and most frequently demonstrated erosive progression. No bones were
      without erosions. Patterns of erosions and progression were similar in early and
      established RA. No major difference between dominant and nondominant wrists was
      detected. In the fingers, the 2nd-3rd MCP joint most frequently displayed
      erosions and erosive progression. CONCLUSION: The distribution and frequency of
      bone erosion and erosive progression as detected by MRI in RA wrists and MCP
      joints were identified. No pattern differences between early versus established
      disease and dominant versus nondominant sides were detected. No bones showed
      erosive progression. Thus, no self-evident simplification of the RAMRIS erosion
      score was identified. Bone involvement patterns may be considered, when joints
      are selected for MRI protocols for clinical trials and practice.

PMID- 21885510
TI  - Damage and progression on radiographs in individual joints: data from pivotal
      randomized controlled trials.
AB  - OBJECTIVE: Radiographic progression is usually assessed by Sharp-based methods
      (van der Heijde-modified Sharp score and the Genant-modified Sharp score). The
      aim of this study was to evaluate, in a range of randomized controlled trials
      (RCT), the presence of erosions and joint space narrowing (JSN) in all individual
      joints, as well as progression in these joints, and to determine if any
      redundancy exists due to infrequently involved joints. METHODS: Four databases of
      rheumatoid arthritis RCT that were all scored according to van der Heijde's
      modification of the Sharp score were included in a descriptive analysis. RESULTS:
      Irrespective of different readers, different patient populations, and different
      disease durations per trial, similar patterns emerged. Both erosions and JSN
      occurred in all sites. Erosions occurred most frequently in the feet,
      preferentially in 5th metatarsophalangeal joint (MTP-5). JSN occurred most
      frequently in the wrist. Change from baseline in erosions and JSN followed the
      pattern of involvement at baseline, so that MTP-5, and to a lesser extent MTP-3
      and MTP-4, preferentially showed progression in erosive damage. Joints in the
      wrist showed highest tendency to worsen over time with respect to JSN.
      CONCLUSION: These data indicate that both erosions and JSN must be assessed for
      damage, and that a more abbreviated joint count cannot be used for radiographic
      scoring.

PMID- 21885511
TI  - Magnetic resonance imaging in rheumatoid arthritis clinical trials: emerging
      patterns based on recent experience.
AB  - OBJECTIVE: The current validated magnetic resonance imaging (MRI) scoring method
      for rheumatoid arthritis (RA) in clinical trials, RA MRI Score (RAMRIS),
      incorporates all metacarpophalangeal (MCP) and wrist joints except MCP-1. The
      experience with radiographic scoring, however, was that excluding certain bones
      in the wrist improved the discriminative power for changes over time. In this
      study, we pool MRI data from randomized controlled clinical trails (RCT) to
      determine which combination of MCP and wrist joints are most sensitive and
      discriminative for structural changes over time. METHODS: MR images from 4
      multicenter RCT, including 522 RA patients, were read by 2 radiologists, using
      the RAMRIS scoring system for erosion, osteitis, and synovitis. In one RCT, joint
      space narrowing (JSN) was assessed cross-sectionally by one radiologist using a
      previously validated method. Baseline frequencies of erosion, JSN, osteitis, and
      synovitis of different bones and joints in the hand and wrist were compared.
      Intraclass correlation coefficients between readers were determined for each
      location. Finally, 7 different combinations of bone/joint locations were compared
      for their ability to discriminate subjects showing increases or decreases from
      baseline greater than or equal to smallest detectable changes (SDC) at Weeks 12
      or 24. RESULTS: Frequency of involvement and reliability for assessing change
      varied by location. As in earlier analyses, excluding certain wrist bones
      increased the percentage of subjects showing changes greater than or equal to
      SDC. CONCLUSION: These findings suggest that excluding wrist bones that do not
      frequently or reliably demonstrate structural changes improves the discriminative
      power of the RAMRIS scoring system.

PMID- 21885512
TI  - Update on research and future directions of the OMERACT MRI inflammatory
      arthritis group.
AB  - The OMERACT Magnetic Resonance Imaging (MRI) Task Force has developed and evolved
      the psoriatic arthritis MRI score (PsAMRIS) over the last few years, and at
      OMERACT 10, presented longitudinal evaluation by multiple readers, using PsA
      datasets obtained from extremity MRI magnets. Further evaluation of this score
      will require more PsA imaging datasets. As well, due to improved image resolution
      since the development of the original rheumatoid arthritis MRI scoring system
      (RAMRIS), the Task Force has worked on semiquantitative assessment of joint space
      narrowing, and developed a reliable method as a potential RAMRIS addendum,
      although responsiveness will need to be evaluated. One of the strengths of MRI is
      the ability to detect subclinical synovitis, so the group worked on obtaining low
      disease activity/clinical remission datasets from a number of international
      centers and presented cross-sectional findings. Subsequent longitudinal
      evaluation of this unique resource will be a major continuing focus for the
      group.

PMID- 21885513
TI  - The OMERACT Psoriatic Arthritis Magnetic Resonance Imaging Score (PsAMRIS) is
      reliable and sensitive to change: results from an OMERACT workshop.
AB  - OBJECTIVE: The aim of this multireader exercise was to assess the reliability and
      sensitivity to change of the psoriatic arthritis magnetic resonance imaging score
      (PsAMRIS) in PsA patients followed for 1 year. METHODS: MRI was acquired from 12
      patients with PsA before initiation of treatment and after 12 months. MR images
      were scored according to PsAMRIS (for synovitis, tenosynovitis, periarticular
      inflammation, bone marrow edema, bone erosion, and bone proliferation) under
      standardized conditions, in unknown chronological order.
      Intraobserver/interobserver reliability was examined by intraclass correlation
      coefficients (ICC) and sensitivity to change by standardized response means
      (SRM). RESULTS: The interobserver reliability of PsAMRIS was high for synovitis,
      tenosynovitis, periarticular inflammation, and bone edema status and change
      scores (interobserver ICC 0.87-0.97). The intraobserver reliability was moderate
      to high (ICC 0.60-0.98) for status and change scores, except for change in
      periarticular inflammation (ICC 0.33). PsAMRIS sensitivity to change was moderate
      for synovitis, tenosynovitis, and periarticular inflammation (SRM 0.5-0.8), while
      poor (SRM 0.1-0.3) for bone marrow edema, erosion, and bone proliferation. Rare
      occurrence and minimal change contributed to poor SRM and change-score ICC for
      bone parameters. CONCLUSION: This multireader exercise, performed under
      standardized conditions, confirmed PsAMRIS to have high interobserver and
      intraobserver reliability for hand PsA. Measures of inflammation were sensitive
      to change, implying that PsAMRIS may be a valuable tool for monitoring change in
      inflammation during PsA clinical trials.

PMID- 21885514
TI  - Synovitis and osteitis are very frequent in rheumatoid arthritis clinical
      remission: results from an MRI study of 294 patients in clinical remission or low
      disease activity state.
AB  - OBJECTIVE: In rheumatoid arthritis (RA), radiographic progression may occur
      despite clinical remission. This may be explained by subclinical inflammation.
      Magnetic resonance imaging (MRI) provides a greater sensitivity than clinical
      examination and radiography for assessing disease activity. Our objective was to
      determine the MRI characteristics of RA patients in clinical remission or low
      disease activity (LDA) state. METHODS: Databases from 6 cohorts were collected
      from 5 international centers. RA patients in clinical remission according to
      Disease Activity Score28-C-reactive protein (DAS28-CRP < 2.6; n = 213) or LDA
      state (2.6 <= DAS28-CRP < 3.2; n = 81) with available MRI data were included. MRI
      were assessed according to the OMERACT RA MRI scoring system (RAMRIS). RESULTS: 
      PATIENT CHARACTERISTICS: 70% women, median age 55 (interquartile range, IQR 43
      63) years, disease duration 2.3 (IQR 0.7-5.1) years, DAS28-CRP 2.2 (IQR 1.8-2.6),
      Simplified Disease Activity Index, SDAI, 3.9 (IQR 1.9-6.5), Clinical Disease
      Activity Index, CDAI, 3.1 (IQR 1.5- 5.8), rheumatoid factor/anti-cyclic
      citrullinated peptide positivity 57%/54%, presence of radiographic erosions: 66%.
      Wrist and metacarpophalangeal MRI (MCP-MRI) data were available for 287 and 241
      patients, respectively. MRI inflammatory activity in wrist and/or MCP joints was
      observed in the majority [synovitis: 95%, bone edema (osteitis): 35%] of
      patients. The median (IQR) RAMRIS score was 6 (3-9) for synovitis and 0 (0-2) for
      osteitis. Synovitis and osteitis were not less frequent in DAS28 clinical
      remission (synovitis/osteitis 96%/35%) than LDA (91/36). A trend towards lower
      frequencies of osteitis in patients in SDAI and CDAI remission was observed.
      CONCLUSION: Subclinical inflammation was identified by MRI in the majority of RA
      patients in clinical remission or LDA state. This may explain structural
      progression in such patients. Further work is required to understand the place of
      modern imaging in future remission criteria.

PMID- 21885515
TI  - Development and preliminary validation of a magnetic resonance imaging joint
      space narrowing score for use in rheumatoid arthritis: potential adjunct to the
      OMERACT RA MRI scoring system.
AB  - OBJECTIVE: To develop and validate a magnetic resonance imaging (MRI) method of
      assessment of joint space narrowing (JSN) in rheumatoid arthritis (RA). METHODS:
      Phase A: JSN was scored 0-4 on MR images of 5 RA patients and 3 controls at 15
      wrist sites and 2nd-5th metacarpophalangeal (MCP) joints by 8 readers (7 once,
      one twice), using a preliminary scoring system. Phase B: Image review,
      discussion, and consensus on JSN definition, and revised scoring system. Phase C:
      MR images of 15 RA patients and 4 controls were scored using revised system by 5
      readers (4 once, one twice), and results compared with radiographs [Sharp-van der
      Heijde (SvdH) method]. RESULTS: Phase A: Intraobserver agreement: intraclass
      correlation coefficient (ICC) = 0.99; smallest detectable difference (SDD, for
      mean of readings) = 2.8 JSN units (4.9% of observed maximal score). Interobserver
      agreement: ICC = 0.93; SDD = 6.4 JSN units (9.9%). Phase B: Agreement was reached
      on JSN definition (reduced joint space width compared to normal, as assessed in a
      slice perpendicular to the joint surface), and revised scoring system (0-4 at 17
      wrist sites and 2nd-5th MCP; 0: none; 1: 1-33%; 2: 34-66%; 3: 67-99%; 4:
      ankylosis). Phase C: Intraobserver agreement: ICC = 0.90; SDD = 6.8 JSN units
      (11.0%). Interobserver agreement: ICC = 0.92 and SDD = 6.2 JSN units (8.7%). The
      correlation (ICC) with the SvdH radiographic JSN score of the wrist/hand was
      0.77. Simplified approaches evaluating fewer joint spaces demonstrated similar
      reliability and correlation with radiographic scores. CONCLUSION: An MRI scoring
      system of JSN in RA wrist and MCP joints was developed and showed construct
      validity and good intra- and interreader agreements. The system may, after
      further validation in longitudinal data sets, be useful as an outcome measure in
      RA.

PMID- 21885516
TI  - OMERACT magnetic resonance imaging initiative on structural and inflammatory
      lesions in ankylosing spondylitis--report of a special interest group at OMERACT
      10 on sacroiliac joint and spine lesions.
AB  - The ASAS/OMERACT MRI group recently described and defined magnetic resonance
      imaging (MRI) findings in sacroiliac joints (SIJ) that are essential for the
      diagnosis of sacroiliitis in patients with axial spondyloarthritis, including
      ankylosing spondylitis (AS). At the Outcome Measures in Rheumatology Clinical
      Trials (OMERACT) 2010 meeting, a special interest group (SIG) was formed to
      design a research agenda for the definition and description of structural lesions
      in the SIJ and the spine in patients with established AS. During the SIG, a
      summary of the previous work of the group was presented to all participants,
      containing: (1) a description of the current definitions of structural SIJ
      changes; (2) available scoring methods for SIJ changes; (3) data from a previous
      pilot MRI exercise on chronic SIJ changes performed by members of the group; and
      (4) a proposal for a research agenda for OMERACT 11. The group agreed on the
      project's scientific merits and the need to evaluate all available scoring
      methods and to have clear definitions for all possible abnormalities that can be
      seen on MRI, prior to the start of the exercise. It was also agreed that the
      exercise should include scoring of both structural and inflammatory lesions, due
      to lack of agreement about the best scoring method for assessing both types of
      lesions in AS. Participants agreed that longitudinal MRI over a certain period
      are needed to learn about the time sequence of pathologic changes and to
      understand the course of the disease. Finally, participants asked the group to
      add the development of a scoring method for structural changes in the spine in a
      subsequent exercise. Further to these objectives, all experts who agreed to
      contribute in the exercise will collaborate to achieve consensus on definitions
      and to organize training in the different scoring systems prior to the start of
      the project, with the aim to finalize the multiple reader exercise by the end of
      2011, in time for OMERACT 11.

PMID- 21885517
TI  - A systematic literature review analysis of ultrasound joint count and scoring
      systems to assess synovitis in rheumatoid arthritis according to the OMERACT
      filter.
AB  - OBJECTIVE: The OMERACT Ultrasound Task Force is currently developing a global
      synovitis score (GLOSS) with the objective of feasibly measuring global disease
      activity in patients with rheumatoid arthritis (RA). In order to determine the
      minimal number of joints to be included in such a scoring system, and to analyze
      the metric properties of proposed global (i.e., patient level) ultrasound (US)
      scoring systems of synovitis in RA, a systematic analysis of the literature was
      performed. METHODS: A systematic literature search of Pubmed and Embase was
      performed (January 1, 1984, to March 31, 2010). Original research reports written
      in English including RA, ultrasound, Doppler, and scoring systems were included.
      The design, subjects, methods, imaging protocols, and performance characteristics
      studied were analyzed, as well as the ultrasound definition of synovitis.
      RESULTS: Of 3004 reports identified, 14 articles were included in the review. We
      found a lack of clear definition of synovitis as well as varying validity data
      with respect to the proposed scores. Scoring systems included a wide range and
      number of joints. All analyzed studies assessed construct validity and
      responsiveness by using clinical examination, laboratory findings, and other
      imaging modalities as comparators. Both construct validity and responsiveness
      varied according to the number and size of joints examined and according to the
      component of synovitis measured [i.e., gray-scale (GS) or power Doppler (PD)
      alone or in combination]. With regard to feasibility, time of evaluation varied
      from 15 to 60 min and increased with the number of joints involved in the
      examination. CONCLUSIONS: Ultrasound can be regarded as a valuable tool for
      globally examining the extent of synovitis in RA. However, it is presently
      difficult to determine a minimal number of joints to be included in a global
      ultrasound score. Further validation of proposed scores is needed.

PMID- 21885518
TI  - The OMERACT ultrasound task force--status and perspectives.
AB  - This article reports the most recent work of the Outcome Measures in Rheumatology
      (OMERACT) Ultrasound Task Force, and highlights the future research priorities
      discussed at the OMERACT 10 meeting. Results of the following studies were
      presented: (1) intra- and interobserver reliability of ultrasound detecting and
      scoring synovitis in different joints of patients with rheumatoid arthritis (RA);
      (2) systematic review of previous ultrasound scoring systems of synovitis in RA;
      (3) enthesitis systematic review and Delphi definition exercise in
      spondyloarthritis enthesitis; (4) enthesitis intra- and interobserver reliability
      exercise; and (5) Delphi definition exercise in hand osteoarthritis, and
      reliability exercises. Study conclusions were discussed, and a future research
      agenda was approved, notably further validation of an OMERACT ultrasound global
      synovitis score (GLOSS) in RA, emphasizing the importance of testing feasibility,
      predictive value, and added value over standard clinical variables. Future
      research areas will include validating scoring systems for enthesitis and
      osteoarthritis, and testing the metric qualities of ultrasound for evaluating
      tenosynovitis and structural damage in RA.

PMID- 21885519
TI  - Synovial tissue analysis for the discovery of diagnostic and prognostic
      biomarkers in patients with early arthritis.
AB  - Rheumatoid arthritis (RA) is a chronic disease of unspecified etiology that is
      manifest by persistent inflammation of the synovium. Considerable efforts have
      been undertaken globally to study the microenvironment of the inflamed synovium,
      with many encouraging and enlightening results that bring us closer to unmasking
      the precise etiologies of RA. Subsequent to these efforts, it has been discovered
      that CD68-positive macrophages present in abundance in the synovial sublining of
      the inflamed synovium rescind with treatments that induce clinical improvement in
      RA. Examination of serial synovial biopsies is now commonly used for screening
      purposes during early drug development, and the number of centers able to perform
      synovial tissue biopsy sampling according to standardized methods is increasing.
      Having implemented the use of serial synovial tissue biopsies to evaluate the
      effects of new treatments on the group level in early proof of principle studies,
      it is the ambition of the OMERACT Synovial Tissue Group to identify synovial
      diagnostic and prognostic biomarkers that could be used in individual patients.
      Therefore, we started a prospective study termed the Synoviomics Project aimed at
      the identification of novel diagnostic and prognostic synovial biomarkers. We
      will use straightforward and powerful technologies to analyze patient material
      and assess clinical parameters to identify such biomarkers. These markers may be
      used in the future to identify patients who are at risk of having persistent and
      destructive disease and to start tailor-made targeted therapies in an early phase
      to prevent autonomous disease progression and irreversible joint damage.

PMID- 21885520
TI  - Subclinical atherosclerosis in ankylosing spondylitis.

PMID- 21885521
TI  - Rheumatoid cachexia: what is it and why is it important?

PMID- 21885522
TI  - The modification of the american college of rheumatology preliminary diagnostic
      criteria for fibromyalgia should be supplemented and revised.

PMID- 21885523
TI  - Prevalence of chronic rheumatic diseases in Mexico.

PMID- 21885524
TI  - Minimal important difference and responsiveness to change of the SF-36 in
      patients with psoriatic arthritis receiving tumor necrosis factor-alpha blockers.

PMID- 21885525
TI  - Effects of iloprost on microvascular structure assessed by nailfold
      videocapillaroscopy: a pilot study.

PMID- 21885526
TI  - Interleukin 6 blockade as steroid-sparing treatment for 2 patients with giant
      cell arteritis.

PMID- 21885527
TI  - Combined pulmonary fibrosis and emphysema syndrome in a patient age 28 years with
      severe systemic sclerosis.

PMID- 21885528
TI  - Marked reduction of sacroiliac joint inflammation on magnetic resonance imaging
      in a patient with ankylosing spondylitis after rituximab treatment.

PMID- 21885531
TI  - Does race influence conflict between nursing home staff and family members of
      residents?
AB  - OBJECTIVES: This study examines the influence of race on perceived similarity and
      conflict between nursing home staff and family members of residents. Despite
      evidence that the caregiving experience varies by race for both family and
      professional caregivers, little is known about how race plays a role in staff
      conflict with residents' family members. METHODS: We used a representative sample
      of Certified Nursing Assistants (CNAs) to test relationships between race,
      treatment from family members, similarity to family members in expectations for
      care by CNAs, and conflicts with family members concerning aspects of resident
      care. RESULTS: Results of structural equation modeling indicated that race was
      not a predictor of staff perception of conflict with family members or of poor
      treatment from residents' families. However, Black nursing assistants were more
      likely to perceive that their own expectations of nursing care are dissimilar
      from those of residents' family members. Dissimilarity predicted reports of poor
      treatment from family members, and poor treatment was a positive predictor of
      perception of conflict. DISCUSSION: The personal long-term nature of nursing home
      care necessitates a high level of connectedness between family caregivers and
      nursing home staff. Results highlight the importance of establishing
      organizational pathways for communication of expectations between nursing staff
      and residents' families.

PMID- 21885532
TI  - Satb2 is required for dendritic arborization and soma spacing in mouse cerebral
      cortex.
AB  - Self-avoidance is a mechanism by which dendrites from the same neuron repel one
      another in order to establish uniform coverage of the dendritic field. The
      importance of self-avoidance for the development of complex arborization patterns
      has been highlighted by studies of Drosophila sensory and mouse retinal neurons.
      However, it is unclear whether branch patterning in the mammalian central nervous
      system is also governed by this strategy. We reduced Satb2 expression in a
      population of layer II/III pyramidal neurons in vivo by RNA interference and
      found that the somas of Satb2-deficient neurons clumped together, and their
      dendrites failed to expand laterally but instead formed fascicles. Furthermore,
      experiments showed that reducing Satb2 caused the adhesion of not only
      neighboring Satb2-deficient neurons but also neighboring wild-type neurons. Our
      results indicate a cell autonomous and non-cell autonomous role for Satb2 in
      regulating the adhesive and/or repulsive properties of cerebral pyramidal
      neurons.

PMID- 21885533
TI  - Website offering orthopaedic second opinions is criticised by surgeons' leaders.

PMID- 21885534
TI  - Brain circuitry model for mental illness will transform management, NIH mental
      health director says.

PMID- 21885535
TI  - Identification of an important site for function of the type 2C protein
      phosphatase ABI2 in abscisic acid signalling in Arabidopsis.
AB  - It is known that the clade A protein phosphatase 2Cs (PP2Cs), including ABI1 and
      ABI2 and other PP2C members, are key players that function directly downstream of
      the PYR/PYL/RCAR abscisic acid (ABA) receptors. Here, identification of a crucial
      site for function of ABI2 protein phosphatase in ABA signalling is reported. It
      was observed that a calcium-dependent protein kinase (CDPK) phosphorylation site
      like motif (CPL) in the ABI2 molecule is required for the interactions of ABI2
      with the two members of the ABA receptors PYL5 and PYL9 and with a downstream
      protein kinase SnRK2.6, and for the catalytic activity of ABI2 in vitro, as well
      as for the response of ABI2 to the ABA receptors PYL5/PYL9 in relation to the ABA
      receptor-induced inhibition of the ABI2 phosphatase activity. Further, genetic
      evidence was provided to demonstrate that this CPL is required for the function
      of ABI2 to mediate ABA signalling. These data reveal that this CPL is an
      important site necessary for both the phosphatase activity of ABI2 and the
      functional interaction between ABI2 and PYL5/9 ABA receptors, providing new
      information to understand primary events of ABA signal transduction.

PMID- 21885537
TI  - Effect of manual lymph drainage in addition to guidelines and exercise therapy on
      arm lymphoedema related to breast cancer: randomised controlled trial.
AB  - OBJECTIVE: To determine the preventive effect of manual lymph drainage on the
      development of lymphoedema related to breast cancer. DESIGN: Randomised single
      blinded controlled trial. SETTING: University Hospitals Leuven, Leuven, Belgium.
      PARTICIPANTS: 160 consecutive patients with breast cancer and unilateral axillary
      lymph node dissection. The randomisation was stratified for body mass index (BMI)
      and axillary irradiation and treatment allocation was concealed. Randomisation
      was done independently from recruitment and treatment. Baseline characteristics
      were comparable between the groups. INTERVENTION: For six months the intervention
      group (n = 79) performed a treatment programme consisting of guidelines about the
      prevention of lymphoedema, exercise therapy, and manual lymph drainage. The
      control group (n = 81) performed the same programme without manual lymph
      drainage. MAIN OUTCOME MEASURES: Cumulative incidence of arm lymphoedema and time
      to develop arm lymphoedema, defined as an increase in arm volume of 200 mL or
      more in the value before surgery. RESULTS: Four patients in the intervention
      group and two in the control group were lost to follow-up. At 12 months after
      surgery, the cumulative incidence rate for arm lymphoedema was comparable between
      the intervention group (24%) and control group (19%) (odds ratio 1.3, 95%
      confidence interval 0.6 to 2.9; P = 0.45). The time to develop arm lymphoedema
      was comparable between the two group during the first year after surgery (hazard
      ratio 1.3, 0.6 to 2.5; P = 0.49). The sample size calculation was based on a
      presumed odds ratio of 0.3, which is not included in the 95% confidence interval.
      This odds ratio was calculated as (presumed cumulative incidence of lymphoedema
      in intervention group/presumed cumulative incidence of no lymphoedema in
      intervention group)*(presumed cumulative incidence of no lymphoedema in control
      group/presumed cumulative incidence of lymphoedema in control group) or
      (10/90)*(70/30). CONCLUSION: Manual lymph drainage in addition to guidelines and
      exercise therapy after axillary lymph node dissection for breast cancer is
      unlikely to have a medium to large effect in reducing the incidence of arm
      lymphoedema in the short term. Trial registration Netherlands Trial Register No
      NTR 1055.

PMID- 21885538
TI  - A comparison of external and internal jugular venous pressures to monitor
      pulmonary artery pressure after superior cavopulmonary anastomosis.
AB  - The internal jugular vein continues to be the preferred site for cannulation to
      monitor central venous pressure despite the reported evidence of the accuracy of
      external jugular venous pressure (EJVP) to reliably predict internal jugular
      venous pressure (IJVP). Internal jugular venous cannulation carries a risk of
      thrombosis that can be life-threatening in children undergoing superior
      cavopulmonary anastomosis and a subsequent Fontan procedure. The present study
      compared IJVP and EJVP in children undergoing superior cavopulmonary anastomosis
      and found no statistical and clinical difference between IJVP and EJVP. Thus,
      external jugular vein cannulation reliably predicts IJVP and pulmonary artery
      pressures in children undergoing superior cavopulmonary anastomosis, and may
      obviate the risk of life-threatening cavopulmonary thrombosis.

PMID- 21885539
TI  - Preserved consciousness in general anesthesia during carotid endarterectomy: a
      six-year experience.
AB  - OBJECTIVES: We prospectively evaluated safety and efficacy from our six-year
      results of general anesthesia (GA) using remifentanil conscious sedation in
      carotid endarterectomy (CEA). METHODS: From January 2005 to December 2010, 625
      consecutive CEAs were performed on 545 patients (male/female 336/209, age 75 +/-
      7 years). After a superficial plexus block with ropavacaine, GA was induced with
      an intravenous infusion of propofol, using local lidocaine during tracheal
      intubation and a high-dose of remifentanil, in all cases reducing and then
      stopping the remifentanil infusion at the clamping time so that the patient would
      be awake and collaborating within a few minutes, as in local anesthesia. Data on
      postoperative morbidity and mortality, neurological complications, shunt
      insertions and the responses to one-day and three-month questionnaires on
      satisfaction were collected for all patients. RESULTS: The 30-day mortality was
      0.32% (two patients). Only one major stroke (0.16%) and two minor strokes (0.32%)
      occurred. A shunt was deployed in 83 cases (13.3%). Eight patients (1.28%)
      reported cranial nerve injuries, and surgical drainage for postoperative hematoma
      was performed in 11 patients (1.8%). Thirty-one patients (4.6%) suffered
      postoperative nausea/vomiting. Almost all patients were satisfied at the 24-h
      (94.6%) and three-month (>98%) follow-up questionnaire. CONCLUSIONS: The six-year
      results for GA using remifentanil conscious sedation were very satisfactory and
      highlighted the advantages of both GA (hemodynamic stability and excellent
      control of ventilation) and local anesthesia (ease of evaluation of neurological
      status) in a calm and relaxed environment for both patient and surgeon.

PMID- 21885540
TI  - Is it safe to stop anticoagulants after successful surgery for atrial
      fibrillation?
AB  - A best evidence topic in cardiothoracic surgery was written according to a
      structured protocol. The question addressed was: is it safe to stop
      anticoagulants after successful surgery for atrial fibrillation? Altogether, 177
      papers were found using the reported search, of which 14 were selected that
      represented the best evidence to answer the clinical question. Selection criteria
      included study relevance, primary outcome, size of study population and length of
      follow-up. The authors, journal, date and country of publication, patient group
      studied, study type, relevant outcomes and results of these papers are tabulated.
      The weight of evidence, including over 10,000 patient-years of follow-up,
      supports the discontinuation of warfarin following atrial fibrillation correction
      procedures as being safe, with an associated annual thromboembolic stroke rate of
      0-3.8% off warfarin, in studies where warfarin was stopped at a mean of 3.6
      months (range 0-8 months) after the procedure. However, the confidence of this
      conclusion suffers from a paucity of high-quality randomized controlled trials in
      the field, with the main body of evidence coming instead from observational non
      randomized studies. The stroke rate also varies with the exact procedure
      performed; pulmonary vein isolation procedures are the most extensively evaluated
      and carry the lowest stroke rate following warfarin discontinuation (0-0.4% per
      annum when performed as an isolated procedure). By contrast, left atrial
      appendage occlusion by insertion of a transcatheter device has an associated
      annual stroke rate of 0-3.8% off warfarin. Thus, discontinuation of warfarin
      following such transcatheter procedures cannot be recommended at this time.
      Concomitant heart surgeries, such as mitral valve repair have been shown to
      increase the thromboembolic rate both unpredictably and dramatically, and this
      review thus identifies concomitant mitral valve surgery as a potentially
      substantial risk factor for late thromboembolic stroke in patients undergoing
      corrective surgeries for atrial fibrillation. This review finds in favour of
      warfarin discontinuation in selected patients at three months post-procedure,
      emphasizing consideration of the patient's individual risk-factor profile as
      paramount. This recommendation is in line with the 2010 guidelines for the
      management of atrial fibrillation produced by the European Society of Cardiology.

PMID- 21885541
TI  - In patients with an enlarged left atrium does left atrial size reduction improve
      maze surgery success?
AB  - A best evidence topic in cardiothoracic surgery was written according to a
      structured protocol. The question addressed was: In [adults undergoing a maze
      procedure for atrial fibrillation (AF)], [does left atrial size reduction]
      compared to [maze surgery alone] improve [maze surgery success]? A total of 58
      papers were found using the reported search, of which eight 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. Four out of eight papers compared a volume
      reduction technique as an adjunct to the maze procedure to a maze procedure alone
      -all four papers reported that atrial volume reduction significantly increased
      restoration of sinus rhythm: 89.3% vs. 67.2%, P<0.001; 85% vs. 68%, P<0.05; 84%
      vs. 68%, P<0.05; 90% vs. 69%, P<0.05. Three out of eight papers had no control
      group but reported good rates of sinus rhythm restoration at last follow-up--90%,
      92% and 89%, respectively--despite the study population including atrial
      enlargement, a risk factor for failure of a maze procedure. One paper reported no
      benefit of an atrial reduction plasty in patients with a left atrium (LA) >70 mm.
      An enlarged LA is a risk factor for failure of a maze procedure, and various
      models of AF suggest that reducing atrial mass and/or diameter may help to
      abolish the re-entry circuits underlying AF. Furthermore, AF is uncommon when
      left atrial diameter is <40 mm, so there is at least some physiological basis for
      atrial reduction surgery in aiding the success of a maze procedure. The evidence
      suggests that patients with an enlarged (>= 55 mm) or giant (>= 75 mm) LA who are
      at risk of failing to obtain sinus conversion after a standard maze procedure may
      derive benefit from concomitant atrial reduction surgery using either a tissue
      excision or a tissue plication technique. However, the evidence is not strong
      since the papers available are not readily comparable owing to substantial
      variations in the populations and procedures involved. We therefore, emphasise
      the need for prospective randomised studies in this area.

PMID- 21885542
TI  - Pulmonary resection after lung transplantation in cystic fibrosis patients.
AB  - Pulmonary resection after lung transplantation in end-stage cystic fibrosis
      presents unique challenges, and scant literature exists to guide physicians. We
      retrospectively reviewed 78 transplants for cystic fibrosis performed between
      2003 and 2008. Fourteen patients underwent posttransplantation pulmonary
      resection. We analyzed the indications, surgical procedures, outcomes, and
      survival. Three pneumonectomies, 4 lobectomies, and 11 wedge resections were
      carried out. We identified 2 groups based on indication: a diagnostic group, and
      a therapeutic group of patients in whom the indications were septic native lung
      in 2, allograft infection in 2, lobar torsion in 2, pulmonary infarction in 2,
      and size mismatch in 4. The mean intensive care unit and hospital stays were 29
      and 50 days, respectively. Four (28.57%) patients died during follow-up,
      including 2 who underwent pneumonectomy; 10 (71.43%) are still alive. Survival
      was 43.43 +/- 8.06 months, and it was not significantly different from that in
      cystic fibrosis patients who had lung transplantation without pulmonary
      resection. Pulmonary resection following lung transplantation in cystic fibrosis
      patients showed acceptable survival and surgical risk, but metachronous
      pneumonectomy was associated with higher mortality.

PMID- 21885543
TI  - Nanofiber-reinforced biological conduit in cardiac surgery: preliminary report.
AB  - Several options are available for right ventricular outflow tract reconstruction,
      including commercially available bovine jugular vein and cryo-preserved
      homografts. Homograft non-availability and the problems of commercially available
      conduits led us to develop indigenously processed bovine jugular vein conduits
      with competent valves. They were made completely acellular and strengthened by
      non-conventional cross-linking without disturbing the extracellular matrix, which
      improved the luminal surface characteristics for hemocompatibility.
      Biocompatibility in vitro and in vivo, along with thermal stability, matrix
      stability, and mechanical strength have been evaluated. Sixty-nine patients
      received these conduits for right ventricular outflow tract reconstruction. Seven
      conduits dilated and 4 required replacement. To counteract dilatation,
      biodegradable polymeric nanofibers in various combinations and in isolation
      (collagen, polycaprolactone, polylactic acid) were characterized and used to
      reinforce the conduit circumferentially. Physical validation by mechanical
      testing, scanning electron microscopy, and in-vitro cytotoxicity was conducted.
      Thermal stability, spectroscopy studies of the polymer, and preclinical studies
      of the coated bovine jugular vein in animals are in progress. The feasibility
      studies have been completed, and the final polymer selection depends on
      evaluation of the functional superiority of the coated bovine jugular vein.

PMID- 21885544
TI  - Sodium thiopental and mean arterial pressure during cardiopulmonary bypass.
AB  - Sodium thiopental is known to have a number of cardiovascular effects, but
      injection into the cardiopulmonary bypass reservoir has not been studied. The
      effect of sodium thiopental on mean arterial blood pressure during
      cardiopulmonary bypass was assessed in 150 patients undergoing elective coronary
      artery bypass grafting. Sodium thiopental 3 mg . kg(-1) was administered via the
      cardiopulmonary bypass reservoir. Mean arterial pressure was recorded just before
      drug administration and at 15-sec intervals up to 120 sec afterwards. Compared to
      the baseline value, mean arterial pressure was significantly higher at 30, 45,
      60, and 75 sec after drug administration, and it was significantly lower at 90,
      105, and 120 sec. Sodium thiopental, in addition to its effects on myocardial
      tissue, acts initially as a potent vasopressor, and shortly after, as a potent
      vasodilator.

PMID- 21885545
TI  - N1 non-small-cell lung cancer. A 20-year surgical experience.
AB  - N1 non-small-cell lung cancer has heterogeneous prognosis in relation to node
      descriptors. There is no agreement on the ideal type of resection. A new
      classification of N1 descriptors was proposed in the 7(th) edition of the TNM
      staging system. A retrospective study was conducted on 384 patients with T1-T3N1
      non-small-cell lung cancer who underwent complete pulmonary resection. The
      prognostic role of N1 descriptors according to the current and new staging
      systems and type of resection was investigated. The 5-year survival rate was 46%.
      Involvement of hilar node stations, multiple stations, and multiple nodes were
      poor prognostic factors (5-year survival, 33%, 21%, and 30%, respectively), as
      well as involvement of the hilar zone and multiple zones (5-year survival, 27%
      and 23%, respectively). Pneumonectomy showed significantly better survival rates
      compared to lobectomy or bilobectomy (5-year survival, 60% vs. 29%). Multivariate
      analysis showed that the number of N1 zones and type of resection were
      independent prognostic factors. Patients with hilar nodal, multiple-level, or
      multiple-zone involvement had poor prognosis. Standard lobectomy remains the
      procedure of choice, but in cases of fixed nodes in the hilar zone, sleeve
      resection or even pneumonectomy should be considered.

PMID- 21885546
TI  - Can invasive thymomas be resected by video-assisted thoracoscopic surgery?
AB  - Although video-assisted thoracic surgery can be used for well-encapsulated
      thymomas, its role in invasive thymomas remains controversial. Between 1998 and
      2009, 77 patients aged 22-76 years underwent thymomectomy by video-assisted
      thoracic surgery. Tumors <5 cm without major invasion on preoperative computed
      tomography were selected. There were 13 invasive thymomas (Masaoka stage III and
      IV). A modified dissection technique was employed to prevent breaching the tumor
      capsule and risking tumor seedling. Limited resection of the phrenic nerve,
      pericardium, perithymic fat, and a wedge of lung was performed en bloc with the
      tumor. The mean duration of surgery was 138 min. Hospital stay was 3.6 days.
      Eleven patients had associated myasthenia gravis. There was 1 case of wound
      infection and no operative mortality. The mean size of the thymomas was 34 mm
      (range, 23-55 mm). All patients had adjuvant radiotherapy. During follow-up of
      4.9 years (range, 1-10 years), there was one local recurrence. With the modified
      video-assisted thoracic surgery technique, selected invasive thymomas detected
      during surgery can be removed safely without resorting to sternotomy.

PMID- 21885547
TI  - Successful management of descending necrotizing mediastinitis.
AB  - Descending necrotizing mediastinitis is a critical infection and the mortality
      rate remains high. Early aggressive surgical drainage and antibiotic therapy are
      essential for treatment. We evaluated the efficiency of transthoracic drainage
      using a minimally invasive technique in 11 cases of descending necrotizing
      mediastinitis between May 2002 and March 2008. We performed a right-side
      minithoracotomy with thoracoscopic assistance, and the mediastinum was thoroughly
      drained. The length of hospitalization ranged from 30 to 117 days. The
      postoperative course was good in all patients, and the outcome was favorable. All
      patients were discharged without major complications. We recommend employing a
      minithoracotomy with thoracoscopic assistance for aggressive treatment of
      descending necrotizing mediastinitis.

PMID- 21885548
TI  - Chordal transfer in rheumatic mitral regurgitation: early experience.
AB  - Chordal transfer and chordal replacement techniques have been quite successful
      for repair of anterior mitral leaflet prolapse in degenerative disease, but
      largely unexplored in rheumatic patients. To extend the scope of valve repair, we
      assessed the chordal transfer technique for correction of anterior mitral leaflet
      prolapse in 57 patients with rheumatic mitral regurgitation, who were treated
      between October 2008 and March 2010. There were 36 women and 21 men with a mean
      age of 25 +/- 7.4 years. Normal chordae and a strip of leaflet tissue were
      transferred from the posterior leaflet to the free edge of the anterior leaflet;
      the posterior leaflet was repaired in the same manner as after quadrangular
      resection. Additional procedures were commissurotomy in 19 patients, aortic valve
      replacement in 1, tricuspid repair in 5, and cryo maze operations in 21. There
      was no hospital mortality. One (1.7%) patient had acute renal failure but
      recovered fully. There was moderate regurgitation in one patient who had
      undergone simultaneous aortic valve replacement. At a mean follow-up of 6.2 +/- 2
      months, 56/57 (98.2%) patients were asymptomatic with no significant mitral
      regurgitation.

PMID- 21885549
TI  - Streptokinase for malignant pleural effusions: a randomized controlled study.
AB  - Effective palliative treatment in malignant pleural effusion can only be carried
      out when the lung is fully expanded after drainage of effusion. We investigated
      the efficacy of intrapleural fibrinolytics for lysing fibrin deposits and
      improving lung reexpansion in patients with malignant pleural effusion. We
      randomly allocated 47 patients with malignant pleural effusion into 2 groups: a
      fibrinolytic group of 24 were given 3 cycles of 250,000 U intrapleural
      streptokinase; the control group of 23 received pleural drainage only.
      Pleurodesis with 5 mg of talc slurry was performed in all patients who had lung
      reexpansion after drainage. Patient characteristics, pleural drainage, lung
      expansion assessed by chest radiography, and pleurodesis outcomes were compared
      between the 2 groups. Patient characteristics were similar in both groups. Lung
      reexpansion was adequate for performing talc pleurodesis in 96% of patients in
      the fibrinolytic group and 74% in the control group. In the fibrinolytic group,
      the mean volume of daily pleural drainage before streptokinase administration was
      425 mL, and it increased significantly to 737 mL after streptokinase infusion.
      Intrapleural administration of streptokinase is advisable for patients with
      malignant pleural effusion.

PMID- 21885551
TI  - Total anomalous pulmonary venous connection beyond infancy.
AB  - Most patients with total anomalous pulmonary venous connection are operated on in
      infancy, with low mortality and morbidity, but in developing countries, we still
      encounter patients beyond infancy. We describe our experience in 26 patients aged
      1-16 years (mean, 5.01 years), with total anomalous pulmonary venous connection,
      who underwent correction between June 2007 and December 2009. Eleven patients
      were >5-years old. Transthoracic echocardiography was diagnostic in all cases.
      Mean intensive care unit stay was 2.3 +/- 0.87 days, and hospital stay was 9.23
      +/- 2.34 days. There were no early deaths and no major postoperative
      complications. Follow-up ranged from 10-40 months. Pulmonary artery pressure, as
      judged by echocardiography, reduced significantly in all patients. Repair of
      total anomalous pulmonary venous connection beyond infancy can be carried out
      safely with acceptable results.

PMID- 21885550
TI  - A high-volume heart transplantation center in an Islamic country.
AB  - Cardiac transplants are performed sporadically or not at all in the majority of
      predominantly Muslim countries in the Middle East. We examined our experience in
      76 patients who underwent heart transplantation between January 2005 and May 2010
      in our center in Saudi Arabia. Excluded were 50 transplants performed between
      1989 and 2004, due to incomplete data. Primary outcomes were complications, 30
      day and late mortality rates, and 1-year survival. The heart transplant activity
      between 2005 and 2010 (15.0 per year) was 4.5-fold higher than that between 1989
      and 2004 (3.3 per year). There were 61 (80%) men and 15 (20%) women, with a mean
      age of 35 years (range, 13-57 years). The mean waiting list time was 64 days
      (range, 1-262 days), and hospital stay was 30 days (range, 12-166 days). Major
      complications were infection (10), low-grade rejection (9), reoperation for
      hemorrhage (8), and sternal dehiscence (2). The 30-day mortality was 7.8% (6/76).
      Actuarial survival was 87.4% at 1 year and 81.5% at 3 years. A hospital in a
      Muslim country can increase cardiac transplant activity with excellent 30-day
      mortality and early survival comparable to that in worldwide counterparts.

PMID- 21885552
TI  - Update on the mitral pulmonary autograft.
AB  - Between July 1997 and August 2004, 92 patients with irreparable mitral valves
      underwent replacement with a pulmonary autograft. This report brings the follow
      up data of these patients up to date. Eighty-eight patients had a successful Ross
      II operation; 4 were lost to follow-up. The mean follow-up period was 94 months.
      Transesophageal echocardiography revealed a successful outcome in all 88 patients
      immediately after the operation. Operative mortality was 4.6%, and late mortality
      definitely related to the operation was 12.5%. At a mean follow-up of 94 months,
      freedom from structural valve deterioration (significant mitral stenosis and/or
      regurgitation) was 93.4%, freedom from reoperation was 92.0%, and freedom from
      all causes of death was 82.9%. Two autografts were explanted because of
      endocarditis. Two patients developed significant pulmonary stenosis, one of whom
      underwent operative repair. These data compare favorably with those of mitral
      valve replacement using modern bioprostheses. This procedure remains an option
      for the relatively young patient when life-long anticoagulation is
      contraindicated or impractical. It is also an option to consider in infants with
      complex irreparable mitral valve disease.

PMID- 21885553
TI  - Epithelioid malignant mesothelioma presenting with features of esophageal tumor.
AB  - Intrathoracic epithelioid mesothelioma commonly presents as a diffuse tumor of
      the pleura. It rarely occurs as a localized tumor that might be surgically
      resectable. We report a case of one such localized mesothelioma in a 72-year-old
      woman, which arose from the wall of the esophagus and had all the presenting
      features of an esophageal tumor.

PMID- 21885554
TI  - Late relapse of non-typhoidal salmonella vascular graft infection after 5 years.
AB  - Salmonella bacteremia can be complicated by mycotic aneurysm with the potential
      for a catastrophic presentation. Treatment involves prompt surgery with
      debridement, extraanatomic bypass, and prolonged antibiotic therapy. Any relapse
      tends to occur within the 1(st) year after surgery. We describe a case of
      Salmonella enteritidis mycotic aneurysm in a 56-year-old man 5 years after the
      initial presentation, emphasizing the importance of aggressive initial therapy
      and long-term surveillance.

PMID- 21885555
TI  - Pseudocoarctation of the aorta complicated by thoracic aortic aneurysm.
AB  - Pseudocoarctation is a rare anomaly involving kinking or buckling of the aorta
      without a pressure gradient across the lesion, considered to be a benign entity
      warranting no specific intervention. An uncommon case of pseudocoarctation
      associated with aortic aneurysm formation in 21-year-old woman is described.
      Pathological findings suggested that the etiology was anomalous development of
      the aorta in association with pseudocoarctation; therefore, careful follow-up of
      patients affected by pseudocoarctation is mandatory.

PMID- 21885556
TI  - Organ procurement: Spanish transplant procurement management.
AB  - Transplantation is an accepted therapeutic option to save or improve the quality
      of life when organ failure occurs or tissue replacements are needed. However, the
      lack of organs is the major limitation. The deceased organ procurement
      organization and professionals provide the solution to this international
      problem. In this review, we identify the elements involved in the organ
      procurement management process to analyze the possibility of implementation of
      deceased organ procurement for a transplantation program. While the donation
      rates are subject to several negative factors including religious, economic,
      cultural, and legal issues, the existence of well-trained professionals may
      considerably increase them. Professional training in organ donation along with
      the establishment of a solid organizational system has been identified as the
      crucial factor in developing efficient organ donation and transplantation
      programs.

PMID- 21885557
TI  - Mitral valve prosthesis implanted in atrial wall over huge calcified annulus.
AB  - We describe an alternative technique for mitral valve replacement in patients
      with severe mitral annular calcification, in whom conventional techniques are not
      feasible. A new annulus that allows supra-annular prosthetic implantation is
      created.

PMID- 21885558
TI  - A tip for keeping the surgical sutures in order during bronchoplasty.
AB  - We describe a device that we use to keep many surgical sutures in order during
      bronchoplasty. This device is torus-shaped with slits at regular intervals
      radially, which encircles the surgical field. We tuck the suture material into
      the slits in the suture runner. Traditionally, they are controlled by the use of
      many mosquito forceps. We believe that this device is useful, and that our method
      is simpler than the traditional method.

PMID- 21885559
TI  - Acute coronary syndrome due to coronary artery-pulmonary artery fistula.

PMID- 21885560
TI  - Cardiac myxoma examined by 320-detector row computed tomography.

PMID- 21885561
TI  - Situs solitus dextrocardia, coarctation, left superior vena cava, sequestration.

PMID- 21885562
TI  - Coronary artery bypass in a patient with complex coronary artery anomaly.

PMID- 21885563
TI  - Should video-assisted surgery be the first-line approach for bronchogenic cysts?

PMID- 21885564
TI  - Chest wall stabilization following mediastinitis.

PMID- 21885565
TI  - Retraction. "A 25-year experience with Carpentier-Edwards Perimount in the mitral
      position".

PMID- 21885566
TI  - The beta-catenin binding protein ICAT modulates androgen receptor activity.
AB  - Androgens have important roles in the development of the prostate gland and in
      prostate cancer. Since the finding that beta-catenin is a cofactor of the
      androgen receptor (AR) and can augment AR signaling, several proteins have been
      found to affect AR signaling through their interaction with beta-catenin. Here,
      we investigated inhibitor of beta-catenin and T-cell factor (ICAT), a beta
      catenin binding protein that inhibits the canonical Wnt/beta-catenin signaling
      pathway, in AR signaling. We demonstrated that expression of ICAT in two AR
      positive prostate cancer cell lines, LNCaP and LAPC4, augments ligand-dependent
      AR-mediated transcription. In contrast, short hairpin RNA knockdown of ICAT and
      beta-catenin specifically blocks enhanced AR-mediated transcription by ICAT.
      Using both stable expression of ICAT and short hairpin RNA knockdown of ICAT
      expression approaches, we further showed that ICAT enhances expression of
      endogenous PSA and KLK2, two androgen response genes, and ligand-induced cell
      growth. In addition, we identified that ICAT and AR can form a ternary complex
      with beta-catenin using in vitro glutathione S-transferase protein pulldown
      assays. Moreover, we detected the endogenous protein complex containing ICAT, AR,
      and beta-catenin in prostate cancer cells using immunoprecipitation assays.
      Recruitment of endogenous ICAT onto the promoter region of the human PSA gene, an
      AR downstream target promoter, was also identified in LNCaP cells. Finally, using
      in vitro protein binding assays, we examined the effect of full-length and
      truncated ICAT on the AR-beta-catenin interaction and observed that addition of
      full-length ICAT retained the interaction between beta-catenin and AR proteins.
      Intriguingly, the truncated ICAT comprising the N-terminal helical domain showed
      a more pronounced effect on beta-catenin binding to AR proteins. Our findings
      suggest a novel molecular mechanism underlying the cross talk between androgen
      and Wnt signaling pathways.

PMID- 21885568
TI  - Challenges in the management of patients with medically unexplained symptoms in
      Poland: a qualitative study.
AB  - BACKGROUND: Patients with medically unexplained symptoms (MUS) are highly
      prevalent in primary care. There are no guidelines for treatment and management
      of this group of patients in the Polish health care system and the establishment
      of a long-term doctor-patient relationship, which is the crux of the therapy, is
      impeded. OBJECTIVE: To establish what challenges Polish GPs encounter while
      dealing with patients with MUS. METHOD: A thematic analysis of 4 focus groups (14
      GPs altogether), using a three-level coding of data. RESULTS: Three main themes
      surfaced in the analysis: negative emotions among the investigated GPs, their
      insufficient training in the management of patients with MUS and the lack of
      guidelines and the influence of the changed health care environment on the
      management of patients with MUS. Four major influences of the changed health care
      environment emerged: GPs' negative image as professionals, barriers to building a
      continuous doctor-patient relationship, limited resources and limited access to
      specialists and lack of a multidisciplinary primary care team. CONCLUSIONS:
      Treatment and management of patients with MUS should make provision for a
      personalized approach to the patient within the Polish primary health care
      system. This can be enhanced by providing additional training in the
      biopsychosocial model during medical education and establishing a GP
      multidisciplinary team. Allocating increased financial resources for primary
      health care and facilitating access to psychologists and psychotherapists could
      also prove beneficial.

PMID- 21885567
TI  - cMyc is a principal upstream driver of beta-cell proliferation in rat insulinoma
      cell lines and is an effective mediator of human beta-cell replication.
AB  - Adult human beta-cells replicate slowly. Also, despite the abundance of rodent
      beta-cell lines, there are no human beta-cell lines for diabetes research or
      therapy. Prior studies in four commonly studied rodent beta-cell lines revealed
      that all four lines displayed an unusual, but strongly reproducible, cell cycle
      signature: an increase in seven G(1)/S molecules, i.e. cyclins A, D3, and E, and
      cdk1, -2, -4, and -6. Here, we explore the upstream mechanism(s) that drive these
      cell cycle changes. Using biochemical, pharmacological and molecular approaches,
      we surveyed potential upstream mitogenic signaling pathways in Ins 1 and RIN
      cells. We used both underexpression and overexpression to assess effects on rat
      and human beta-cell proliferation, survival and cell cycle control. Our results
      indicate that cMyc is: 1) uniquely up-regulated among other candidates; 2)
      principally responsible for the increase in the seven G(1)/S molecules; and, 3)
      largely responsible for proliferation in rat beta-cell lines. Importantly, cMyc
      expression in beta-cell lines, although some 5- to 7-fold higher than normal rat
      beta-cells, is far below the levels (75- to 150-fold) previously associated with
      beta-cell death and dedifferentiation. Notably, modest overexpression of cMyc is
      able to drive proliferation without cell death in normal rat and human beta
      cells. We conclude that cMyc is an important driver of replication in the two
      most commonly employed rat beta-cell lines. These studies reverse the current
      paradigm in which cMyc overexpression is inevitably associated with beta-cell
      death and dedifferentiation. The cMyc pathway provides potential approaches,
      targets, and tools for driving and sustaining human beta-cell replication.

PMID- 21885569
TI  - A qualitative study on patients' and physicians' visions for the future
      management of overweight or obesity.
AB  - BACKGROUND: The management of obesity with its associated morbidity and mortality
      is a growing problem in primary care practices. Despite numerous recommendations
      in response to this challenge, weight management interventions still yield poor
      results. This is partly due to a discrepancy between physicians' and patients'
      understanding of the problem and possible solutions. OBJECTIVE: This study
      analyses patients' and physicians' visions for the future management of obesity.
      METHODS: Qualitative in-depth semi-structured interviews were performed.
      Physicians and patients were asked about their individual needs, experience and
      views regarding the management of obesity. Fifteen GPs and 15 overweight patients
      participated in this study. Interviews were transcribed and submitted to
      qualitative content analysis. RESULTS: The investigation reveals a high level of
      agreement between the two groups with regard to communication requirements for
      successful care. Both groups stressed the need for multimodal care concepts
      inside and outside of GP practices. Both also addressed the current overburdening
      of outpatient care structures in dealing with the management of obesity.
      CONCLUSION: Options should be developed for closer cooperation between GPs and
      support facilities inside and outside practices.

PMID- 21885570
TI  - Acceptability of a guided self-help mental health intervention in general
      practice.
AB  - BACKGROUND: People with subthreshold mental health syndromes are common in
      general practice and represent an important morbidity and disability burden.
      Management options are currently limited. We examined the acceptability of a
      novel ultra-brief guided self-help intervention designed specifically for use in
      this setting. OBJECTIVE: To assess clinician and patient satisfaction with an
      ultra-brief guided self-help intervention to address subthreshold mental health
      syndromes in the primary care setting. METHODS: Consenting patients were given
      the ultra-brief intervention in a series of three 15- to 30-minute coaching
      sessions over a 5-week period. DESIGN: survey interview of clinician and patient
      satisfaction with and acceptability of the intervention. SETTING: general
      practices in Wellington, New Zealand. MAIN OUTCOME MEASURE: clinician and patient
      acceptability of the intervention was assessed by survey questionnaire at 3
      months. Baseline and follow-up mental health status assessments were undertaken
      using the Kessler-10 measure of psychological distress. RESULTS: Six clinicians
      recruited 19 patient participants, 16 of whom completed the intervention. Based
      on questionnaire feedback, clinician and patient satisfaction ratings were very
      positive. However, clinicians expressed a concern that the length of the sessions
      was sometimes inadequate. The psychological well-being of the patients, as
      measured by the Kessler-10, was also significantly improved post-intervention.
      CONCLUSION: The intervention appeared to improve the psychological well-being of
      the patients and was regarded positively by both clinicians and patient
      participants. Further testing of the efficacy of the intervention on a larger
      sample with a randomized controlled trial study design is warranted.

PMID- 21885572
TI  - AFLP fingerprinting shows that a single Prymnesium parvum harmful algal bloom
      consists of multiple clones.
AB  - Due to slow rates of molecular evolution, DNA sequences used to identify and
      build phylogenies of algal species involved in harmful algal blooms (HABs) are
      generally invariant at the intraspecific level. This means that it is unknown
      whether HAB events result from the growth of a single clone, a few dominant
      clones, or multiple clones. This is true despite the fact that several
      physiological and demographic traits, as well as toxicity, are known to vary
      across clones. We generated AFLP fingerprints from a set of 6 clonal isolates,
      taken from a bloom of Prymnesium parvum at a striped bass mariculture facility.
      This new haptophyte bloom was recently implicated in fish kills at several sites
      in the United States. The AFLP fragments were highly reproducible and showed that
      all isolates were distinguishable due to abundant AFLPs unique to single
      isolates. These results demonstrate that blooms can be genetically diverse
      outbreaks and indicate that AFLP can be a powerful molecular tool for
      characterizing and monitoring this diversity.

PMID- 21885571
TI  - Genetic structure and the North American postglacial expansion of the barnacle,
      Semibalanus balanoides.
AB  - Population genetic characteristics are shaped by the life-history traits of
      organisms and the geologic history of their habitat. This study provides a
      neutral framework for understanding the population dynamics and opportunities for
      selection in Semibalanus balanoides, a species that figures prominently in
      ecological and evolutionary studies in the Atlantic intertidal. We used
      mitochondrial DNA (mtDNA) control region (N = 131) and microsatellite markers
      (~40 individuals/site/locus) to survey populations of the broadly dispersing
      acorn barnacle from 8 sites spanning 800 km of North American coast and 1 site in
      Europe. Patterns of mtDNA sequence evolution were consistent with larger
      population sizes in Europe and population expansion at the conclusion of the last
      ice age, approximately 20 000 years ago, in North America. A significant portion
      of mitochondrial diversity was partitioned between the continents (phi(ST) =
      0.281), but there was only weak structure observed from mtDNA within North
      America. Microsatellites showed significant structuring between the continents
      (F(ST) = 0.021) as well as within North America (F(ST) = 0.013). Isolation by
      distance in North America was largely driven by a split between populations south
      of Cape Cod and all others (P < 10(-4)). The glacial events responsible for
      generating allelic diversity at mtDNA and microsatellites may also be responsible
      for generating selectable variation at metabolic enzymes in S. balanoides.

PMID- 21885574
TI  - Substance use and first-episode psychosis.

PMID- 21885573
TI  - Temporal population genetic structure of eastern mosquitofish in a dynamic
      aquatic landscape.
AB  - We analyzed the effect of periodic drying in the Florida Everglades on
      spatiotemporal population genetic structure of eastern mosquitofish (Gambusia
      holbrooki). Severe periodic drying events force individuals from disparate
      sources to mix in dry season relatively deep-water refuges. In 1996 (a wet year)
      and 1999 (a dry year), we sampled mosquitofish at 20 dry-season refuges
      distributed in 3 water management regions and characterized genetic variation for
      10 allozyme and 3 microsatellite loci. In 1996, most of the ecosystem did not
      dry, whereas in 1999, many of our sampling locations were isolated by expanses of
      dried marsh surface. In 1996, most spatial genetic variation was attributed to
      heterogeneity within regions. In 1999, spatial genetic variation within regions
      was not significant. In both years, a small but significant amount of variation
      (less than 1% of the total variation) was partitioned among regions. Variance was
      consistently greater than zero among long-hydroperiod sites within a region, but
      not among short-hydroperiod sites within a region, where hydroperiod was measured
      as time since last marsh surface dry-down forcing fishes into local refuges. In
      1996, all sites were in Hardy-Weinberg equilibrium. In 1999, we observed fewer
      heterozygotes than expected for most loci and sites suggesting a Wahlund effect
      arising from fish leaving areas that dried and mixing in deep-water refuges.

PMID- 21885575
TI  - Best practices: Optimizing care for people with serious mental illness and
      comorbid diabetes.
AB  - Diabetes and obesity among patients with serious mental illness are common. Use
      of second-generation antipsychotics compounds risk, and widely prevalent
      unhealthy behaviors further contribute to negative outcomes. This column
      describes Targeted Training in Illness Management, a group-based psychosocial
      treatment that blends psychoeducation, problem identification, goal setting, and
      behavioral modeling and reinforcement. The intervention has been adapted to the
      primary care setting and is targeted at individuals with serious mental illness
      and diabetes. A key feature of the intervention is the use of peer educators with
      serious mental illness and diabetes to teach and model self-management. Promising
      results from a 16-week trial are reported.

PMID- 21885576
TI  - Public-academic partnerships: a program to improve the quality of antipsychotic
      prescribing in a community mental health system.
AB  - State mental health authorities can use public-academic partnerships to create
      professional roles in which leaders can track trends, identify problems, and
      carry out quality improvement projects to address key issues. Leaders with
      positions in both academic institutions and state mental health authorities
      ensure access to resources, technical expertise, and key relationships to improve
      quality. The authors describe a public-academic partnership in New Hampshire and
      a quality improvement program it carried out. The program encourages providers at
      community mental health centers to adopt prescribing practices that limit the
      cardiometabolic side effects of antipsychotic medicines.

PMID- 21885578
TI  - Career satisfaction of psychiatrists.
AB  - OBJECTIVE: According to recent estimates, there is a shortage of around 45,000
      psychiatrists in the United States. It will be very difficult to address this
      problem without attracting more medical students to psychiatry and motivating the
      current crop of psychiatrists to see more patients and delay retirement. In this
      study the authors sought to identify factors that have a significant impact on
      the career satisfaction of psychiatrists. METHODS: Data were gathered from 314
      psychiatrists who participated in the 2008 Health Tracking Physician Survey
      conducted by the Center for Studying Health System Change. Independent variables
      were grouped as practice-related factors, compensation-related factors, patient
      related factors, and demographic characteristics of psychiatrists. Career
      satisfaction of psychiatrists was the outcome measure of this study. RESULTS:
      Threat of malpractice and the need to consider in treatment decisions out-of
      pocket cost to patients had a significant negative impact on career satisfaction.
      Adequate time with a patient had a significant positive impact on career
      satisfaction. None of the compensation-related factors was significant.
      Psychiatrists who worked in practices that accepted new Medicare patients
      reported significantly higher levels of career dissatisfaction, whereas those who
      worked in practices that accepted new Medicaid patients reported significantly
      higher levels of career satisfaction. Older psychiatrists were more satisfied
      than younger psychiatrists, and white, non-Hispanic psychiatrists were more
      satisfied than African-American or Hispanic psychiatrists. CONCLUSIONS: The
      results of this study highlight the need for policy makers and health care
      administrators to develop specific strategies to increase career satisfaction,
      which in return may help alleviate the shortage of psychiatrists.

PMID- 21885577
TI  - Substance use disorder among people with first-episode psychosis: a systematic
      review of course and treatment.
AB  - OBJECTIVE: People experiencing a first episode of psychosis frequently have co
      occurring substance use disorders, usually involving alcohol and cannabis, which
      put them at risk for prolonged psychosis, psychotic relapse, and other adverse
      outcomes. Yet few studies of first-episode psychosis have addressed the course of
      substance use disorders and the response to specialized substance abuse
      treatments. METHODS: The authors searched MEDLINE, PsycINFO, and other medical
      databases for English-language articles published between 1990 and 2009. Included
      studies addressed two research questions. First, do some clients become abstinent
      after a first episode of psychosis without specialized substance abuse
      treatments? Second, for clients who continue to use substances after a first
      episode of psychosis, does the addition of specialized substance abuse treatment
      enhance outcomes? RESULTS: Nine studies without specialized substance abuse
      treatment and five with specialized substance abuse treatment assessed the course
      of substance use (primarily cannabis and alcohol) after a first episode of
      psychosis. Many clients (approximately half) became abstinent or significantly
      reduced their alcohol and drug use after a first episode of psychosis. The few
      available studies of specialized substance abuse treatments did not find better
      rates of abstinence or reduction. CONCLUSIONS: Experience, education, treatment,
      or other factors led many clients to curtail their substance use disorders after
      a first episode of psychosis. Specialized interventions for others need to be
      developed and tested.

PMID- 21885579
TI  - Racial-ethnic composition of provider practices and disparities in treatment of
      depression and anxiety, 2003-2007.
AB  - OBJECTIVES: This study explored whether racial and ethnic disparities in the
      treatment of depression and anxiety are associated with provider-level factors.
      METHODS: This study analyzed 58,826 office-based adult outpatient visits to
      primary care physicians and psychiatrists. Data were from the National Ambulatory
      Medical Care Survey, 2003-2007. Outcomes included counseling and referral for
      counseling, antidepressant prescription, and any care for depression or anxiety.
      The analyses of treatment outcomes were not limited to visits with a depression
      or anxiety diagnosis. RESULTS: Compared with visits to primary care physicians by
      whites, such visits by blacks and Hispanics were less likely to result in
      antidepressant prescription or in any care for depression or anxiety; primary
      care visits by Hispanics were also less likely to result in counseling. Compared
      with visits to psychiatrists by whites, such visits by blacks were less likely to
      result in an antidepressant prescription. The majority of visits to both primary
      care physicians and psychiatrists by blacks and Hispanics were to practices
      serving a high percentage of nonwhite patients. However, racial and ethnic
      disparities in care that were especially evident in primary care settings
      persisted after the analyses controlled for whether visits were to settings with
      a high or low percentage of nonwhite patients. CONCLUSIONS: Disparities in care
      for depression and anxiety in primary care continue and are not fully accounted
      for by less care being provided in settings that nonwhites frequent. Physician
      bias, resource issues, and patient factors may all play a role in the diagnosis
      and treatment of depression and anxiety.

PMID- 21885580
TI  - Ethnic disparities in antipsychotic drug use in British Columbia: a cross
      sectional retrospective study.
AB  - OBJECTIVE: This study examined ethnic disparities in antipsychotic therapy in a
      population with significant Asian representation. METHODS: Using a cross
      sectional retrospective study design, self-reported ethnicity data pooled from
      three cycles of the Canadian Community Health Survey were linked to 2005
      administrative data on physician, hospital, and pharmaceutical use in British
      Columbia, Canada. Logistic regression was used to model the association between
      ethnicity and the likelihood of filling one or more prescriptions for any
      antipsychotic, with controls for sex, age, residence, immigrant status, income,
      health status, and diagnoses of schizophrenia, bipolar disorder, depression, and
      dementia. RESULTS: Of the 27,658 individuals in the sample, 2.2% filled at least
      one antipsychotic prescription. The proportion varied across ethnic groups:
      Chinese, 1.0%; other Asians, 1.2%; whites, 2.3%; nonwhite non-Asians, 2.8%; and
      mixed ethnicity, 4.3%. After adjustment for patient characteristics and diagnoses
      of schizophrenia and bipolar disorder, the likelihood of filling a prescription
      was found to be lower among Chinese (odds ratio [OR] = .47, 95% confidence
      interval [CI] = .24-.90) and higher among persons of mixed ethnicity (OR = 3.19,
      CI = 1.49-6.83). Further adjustment for depression and dementia diagnoses did not
      significantly change the ORs for the Chinese (OR = .49, CI = .25-.98) and the
      mixed ethnic groups (OR = 2.97, CI = 1.30-6.80). CONCLUSIONS: Consistent with the
      existing literature on ethnic disparities in antipsychotic therapy, the study
      found evidence of persistent disparities in a population that has a significant
      number of Asians. Further studies should be done to identify possible causes of
      these disparities and to identify potential interventions that may reduce or
      eliminate them.

PMID- 21885581
TI  - Adherence, persistence of use, and costs associated with second-generation
      antipsychotics for bipolar disorder.
AB  - OBJECTIVE: A retrospective study using Medicaid claims identified patients with
      bipolar disorder for whom oral second-generation antipsychotics were prescribed
      and compared rates of adherence, persistence of use, and costs across five groups
      of patients taking aripiprazole, olanzapine, quetiapine, risperidone, or
      ziprasidone. METHODS: Medicaid claims data for 2,446 bipolar patients were
      analyzed from eight states. The 18-month observation period included the six
      months before and the 12 months after the index prescription date. Adherence was
      defined as a medication possession ratio >80%. Persistence of use was measured by
      the number of days of medication therapy before a 30-day gap. Mental health
      related prescription costs, total prescription costs, total mental health-related
      costs, and total costs were assessed. Ziprasidone was the comparator. RESULTS:
      Clinically recommended doses of second-generation antipsychotic medications were
      prescribed for 45% of the patients (N = 1,102). Of these, 58% (N = 642 of 1,102)
      were adherent with the prescribed medication, with no significant differences
      between medication groups. Median time to nonpersistence of use averaged 96 days.
      Patients taking olanzapine were about 35% more likely than patients taking
      ziprasidone to discontinue taking their medication (hazard ratio = 1.34, 95%
      confidence interval = 1.02-1.76, p = .04). Mental health-related prescription
      costs and total prescription costs were lower for risperidone than ziprasidone.
      No statistically significant differences were found between the groups for all
      mental health-related costs or total costs. CONCLUSIONS: Among patients in a
      sizeable Medicaid cohort for whom a second-generation antipsychotic medication
      was prescribed, less than half had a clinically recommended dose, and less than
      two-thirds with a clinically recommended dose were adherent to the medication,
      confirming that many patients with bipolar disorder do not receive clinically
      recommended doses of second-generation antipsychotics.

PMID- 21885582
TI  - Characteristics associated with purchasing antidepressant or antianxiety
      medications through primary care in Israel.
AB  - OBJECTIVES: This study analyzed the role of patient and physician characteristics
      associated with the purchase of antidepressant or antianxiety medications in
      Israel, a country that has a universal health care system. METHODS: A national
      sample of 30,000 primary care patients over the age of 22 was randomly drawn from
      the registry of the largest health care fund in Israel. Data concerning
      medication purchase between January and December 2006 were extracted. Physician
      and patient characteristics were merged with Israel's unique identification
      number. Multilevel analysis was conducted to identify patient- and physician
      level predictors of medication purchase. RESULTS: Overall, 19% (N = 4,762) of the
      sample purchased antidepressant or antianxiety medications. Individuals with
      greater general medical and psychiatric comorbidity were more likely to purchase
      antidepressant or antianxiety medications. Older adults, women, those of higher
      socioeconomic status, and immigrants (with the exception of Jews born in Asia or
      Africa) were also more likely to purchase medications. Arabs and Jews born in
      Asia and Africa were less likely to purchase medications even after all other
      variables were accounted for. Physician characteristics were minimally associated
      with the purchase of medications. CONCLUSIONS: The findings demonstrate that
      despite universal health care access, there were variations by population groups.
      Educational efforts should target patients as well as physicians.

PMID- 21885583
TI  - Implementation of collaborative depression management at community-based primary
      care clinics: an evaluation.
AB  - OBJECTIVE: This study evaluated a large demonstration project of collaborative
      care of depression at community health centers by examining the role of clinic
      site on two measures of quality care (early follow-up and appropriate
      pharmacotherapy) and on improvement of symptoms (score on Patient Health
      Questionnaire-9 reduced by 50% or <= 5). METHODS: A quasi-experimental study
      examined data on the treatment of 2,821 patients aged 18 and older with
      depression symptoms between 2006 and 2009 at six community health organizations
      selected in a competitive process to implement a model of collaborative care. The
      model's key elements were use of a Web-based disease registry to track patients,
      care management to support primary care providers and offer proactive follow-up
      of patients, and organized psychiatric consultation. RESULTS: Across all sites, a
      plurality of patients achieved meaningful improvement in depression, and in many
      sites, improvement occurred rapidly. After adjustment for patient
      characteristics, multivariate logistic regression models revealed significant
      differences across clinics in the probability of receiving early follow-up (range
      .34-.88) or appropriate pharmacotherapy (range .27-.69) and in experiencing
      improvement (.36 to .84). Similarly, after adjustment for patient
      characteristics, Cox proportional hazards models revealed that time elapsed
      between first evaluation and the occurrence of improvement differed significantly
      across clinics (p<.001). CONCLUSIONS: Despite receiving similar training and
      resources, organizations exhibited substantial variability in enacting change in
      clinical care systems, as evidenced by both quality indicators and outcomes.
      Sites that performed better on quality indicators had better outcomes, and the
      differences were not attributable to patients' characteristics.

PMID- 21885584
TI  - Perceptions of quality of health care among veterans with psychiatric disorders.
AB  - OBJECTIVE: An estimated 37% to 40% of veterans treated by the U.S. Department of
      Veterans Affairs (VA) have a psychiatric disorder, and many of them have comorbid
      general medical problems. This study examined the impact of demographic and
      clinical characteristics on perceptions of outpatient health care experiences
      among veterans with psychiatric disorders. METHODS: Responses from the Survey of
      Health Care Experiences (SHEP) administered by the Veterans Health Administration
      (VHA) and administrative data from the VA were collected for 55,578 patients aged
      18 and older with a psychiatric disorder surveyed in fiscal year 2005. Bivariate
      and multivariable analyses were used to examine the associations between
      demographic and clinical characteristics and patients' responses about providers'
      attentiveness, collaboration in health care decisions, confidence in providers,
      and overall quality of care. RESULTS: Most veterans with psychiatric disorders
      perceived their health care experiences positively. However, those who were
      younger, were nonwhite, had lower incomes, had a service-connected disability,
      and had been diagnosed as having PTSD or a substance use disorder were less
      likely to perceive their health care experiences positively. CONCLUSIONS: An
      opportunity exists to improve clinical practice and design health care services
      to better serve certain groups of patients at VHA facilities. Areas of
      improvement may include rapport building and developing ways to include patients
      in decisions about their health care.

PMID- 21885585
TI  - Association of involuntary psychiatric examination with probability of arrest of
      people with serious mental illness.
AB  - OBJECTIVE: This study examined the association between the occurrence of an
      involuntary psychiatric examination under Florida civil commitment law and the
      probability of arrest during the next quarter. METHODS: County criminal justice
      records and several statewide and local health and social service data sets were
      used to identify inmates with a serious mental illness who spent at least one day
      in the Pinellas County jail between July 1, 2003, and June 30, 2004. These same
      data sets were combined with statewide arrest and prison records to identify the
      criminal justice and health and social services histories of these individuals
      from July 1, 2002, to June 10, 2006, with the four-year period divided into 16
      periods of 90 days. The main analysis used individual fixed-effects models to
      examine the relationship between involuntary examinations and subsequent
      probability of arrest. RESULTS: There were 3,728 inmates with serious mental
      illness in the sample, with 40% (N = 1,485) having at least one involuntary
      examination during the four-year period. Individuals who experienced an
      involuntary examination during the four years were arrested in 34% (N = 1,038) of
      the quarters after an examination and in 27% (N = 3,786) of the quarters not
      preceded by an involuntary examination. Individual fixed-effects models found a
      significant positive relationship between the receipt of an involuntary
      examination in one period and the likelihood of arrests, felony arrests, and
      misdemeanor arrests in the next period. CONCLUSIONS: Involuntary psychiatric
      examinations were associated with increased risk of arrest. Thus an involuntary
      examination was a significant signal that individuals with serious mental illness
      were at risk for criminal behavior and arrest.

PMID- 21885586
TI  - Service intensity as a predictor of competitive employment in an individual
      placement and support model.
AB  - OBJECTIVES: Previous research on the individual placement and support (IPS) model
      of supported employment has focused on the model's effectiveness and on fidelity
      to the program model. Little is known about service intensity, or the number of
      service contacts received. This study examined several aspects of service
      intensity: average level, association with weeks worked, predictors, and
      modulators of its effect on weeks worked. METHODS: The study used data that were
      collected over two years from 91 persons with severe mental illness who
      participated in one arm of a randomized controlled trial conducted at Thresholds,
      a psychosocial rehabilitation center in Chicago. RESULTS: Services were more
      intense during the initial phase of services, service intensity predicted later
      weeks worked, and few individual demographic and clinical characteristics were
      related to service intensity. Finally, high levels of cognitive symptoms weakened
      the relationship between service intensity and weeks worked. CONCLUSIONS: This
      study suggests increased IPS service intensity may lead to better employment
      outcomes and has implications for service provision and fidelity measurement.

PMID- 21885587
TI  - Direct costs of bipolar disorder versus other chronic conditions: an employer
      based health plan analysis.
AB  - OBJECTIVE: This study was a retrospective data-based analysis of health care
      utilization and costs for patients diagnosed as having bipolar disorder compared
      with patients with diagnoses of depression, diabetes, coronary artery disease, or
      asthma. METHODS: Data were from an employer-based health plan. Consistent
      diagnosis and continuous enrollment from 2004 to 2007 were used to identify the
      study population (total N = 7,511), including those with bipolar disorder (N =
      122), depression (N = 1,290), asthma (N = 2,770), coronary artery disease (N =
      1,759), diabetes (N = 1,418), and diabetes with coronary artery disease (N =
      455). Resource utilization quantified as cost (total, specialty care, psychiatric
      outpatient) and number of visits (specialty care and outpatient psychiatric care)
      was compared across groups. RESULTS: Patients with bipolar disorder had higher
      adjusted mean per member per month (PMPM) costs than any other comparison group
      except for those with both diabetes and coronary artery disease. The cost was
      predominantly related to pharmacy costs and both inpatient and outpatient
      psychiatric care. A subset of 20% of patients with bipolar disorder accounted for
      64% of the total costs. This subgroup of patients was more likely to be female,
      to have frequent hospital stays, and to have a higher number of comorbidities.
      Depressed patients, in contrast to bipolar disorder patients, had higher adjusted
      mean PMPM costs in primary care and nonpsychiatric inpatient costs. CONCLUSIONS:
      Health care costs for bipolar disorder exceeded those for several common chronic
      illnesses. These data provide further evidence for employers, insurers, and
      providers to seek innovative models to deliver effective and efficient care to
      individuals with bipolar illness.

PMID- 21885588
TI  - Adequacy of treatment for patients with schizophrenia spectrum disorders and
      affective disorders in Lombardy, Italy.
AB  - OBJECTIVE: This study assessed whether patients being treated for schizophrenia
      spectrum and affective disorders in Lombardy receive adequate treatment and
      sought predictors of adequate treatment. METHODS: Patients were aged >= 18, were
      residents of Italy's Lombardy region, and were treated in 2007 for schizophrenia
      spectrum and affective disorders (N = 44,462). The patients were assessed as part
      of a retrospective analysis of pharmaceutical and mental health services
      databases. Adequacy of 12-month treatment from the first psychiatric contact in
      2007 was assessed at the patient level. A hierarchical log-binomial regression
      model was fitted to estimate relative risk and 95% confidence intervals for
      association between patients, characteristics of the departments of mental health
      (DMH), and receipt of minimally adequate treatment. RESULTS: About half the
      patients with serious mental disorders did not receive adequate care; 45.5% of
      patients with depressive disorders, 55.7% of those with bipolar disorders, and
      49.3% of those with schizophrenia spectrum disorders received minimally adequate
      treatment. Diagnosis of a schizophrenia spectrum disorder or bipolar disorder and
      male gender predicted adequate treatment, whereas employment and high comorbidity
      predicted inadequate treatment. Patients who received mental health services in
      the past year were significantly more likely to receive adequate treatment
      compared with those who had received services in the past five years or new
      patients. CONCLUSIONS: Minimally adequate treatment is a useful indicator to
      monitor quality of care in Italy's regional mental health system. These data
      should be used at regional and local levels to implement clinical audits, to
      create benchmark measures, and to define new quality-improvement projects to meet
      specific DMH needs.

PMID- 21885589
TI  - Lessons learned from the New York State mental health response to the September
      11, 2001, attacks.
AB  - OBJECTIVE: In the aftermath of the September 11, 2001, attacks on the World Trade
      Center, the public mental health system in New York City mounted the largest
      mental health disaster response in history, called Project Liberty. The successes
      and challenges of Project Liberty are evaluated. METHODS: The development of
      Project Liberty is summarized and analyzed from the perspective of the New York
      State and New York City officials and scientists who led the disaster response.
      Lessons learned that have implications for mental health support in future
      disaster responses are offered. RESULTS: A high level of interagency
      collaboration, engagement of nongovernmental organizations to provide services,
      media education efforts, and ongoing program evaluation all contributed to the
      program's successes. Mental health professionals' limited experiences with
      trauma, options for funding treatment, duration of clinical program, and existing
      needs assessments methodologies all proved challenging. CONCLUSIONS: Project
      Liberty was a massive and invaluable resource during the years of rebuilding in
      New York City in the wake of the attacks. Challenges faced have led to lessons of
      generalizable import for other mental health responses to large-scale events.

PMID- 21885590
TI  - CMHC adherence to National Mental Health Plan standards in Italy: a survey 30
      years after national reform law.
AB  - OBJECTIVE: The PROG-CSM (Progetto Centri di Salute Mentale) survey was conducted
      in all Italian community mental health centers (CMHCs) with the aim of evaluating
      the extent to which these services adhered to the standards defined by the
      Italian National Mental Health Plan 1998-2000. METHODS: The policy
      recommendations of the Italian National Mental Health Plan were translated by a
      multidisciplinary group of experts into key indicators, including continuity of
      care, coordination with other community-based services, accessibility,
      implementation of specific programs, and provision of care. RESULTS: There was
      high adherence to the standards of the National Mental Health Plan in continuity
      of care and coordination with other services, but there were lower levels of
      accessibility and implementation of specific projects. CONCLUSIONS: CMHCs were
      sufficiently developed throughout Italy, and continuity of care and service
      coordination levels were satisfactory; however, adherence to the standards was
      unrelated to the duration of activity of the CMHCs.

PMID- 21885591
TI  - Use of administrative data to identify potential service gaps for individuals
      with serious mental illness.
AB  - OBJECTIVE: The New York City Mental Health Care Monitoring Initiative uses
      Medicaid claims data to identify individuals with serious mental illness who are
      experiencing or at risk for gaps in services. In this study the authors assessed
      whether proposed service use algorithms accurately identified such individuals.
      METHODS: A random sample of 500 individuals with serious mental illness was
      identified. Individuals belonged to specific high-need cohorts and met predefined
      claims-based criteria for potential service gaps. Clinical staff initiated
      reviews with prior service providers for 230 individuals. RESULTS: Over a two
      week period staff completed reviews for 188 cases (88%). In 66 cases (35%) the
      individual was fully engaged in care; 84 (45%) had a recent episode of
      disengagement that was appropriately addressed, and 38 (20%) were not receiving
      adequate services. CONCLUSIONS: The proposed service use algorithms successfully
      identified high-need individuals with serious mental illness at risk for gaps in
      services.

PMID- 21885592
TI  - Medical comorbidity and functional status among adults with major mental illness
      newly admitted to nursing homes.
AB  - OBJECTIVE: This study compared comorbid conditions and functional status among
      elderly and nonelderly individuals with mental illness who were newly admitted to
      nursing homes (N = 286,411). METHODS: Data were drawn from the Centers for
      Medicare & Medicaid Services national registry of nursing home residents from the
      Minimum Data Set in 2008. RESULTS: Among newly admitted individuals with
      schizophrenia, those younger than 65 accounted for a majority (60.3%) of
      admissions and had lower rates of medical illnesses and were more likely to be
      classified as low-care status than individuals who were 65 or older. Most (81%)
      new admissions with depression were 65 or older. Among all nonelderly admissions,
      individuals with depression had the highest rates of medical comorbidity.
      CONCLUSIONS: Many adults younger than 65 with schizophrenia who were newly
      admitted to nursing homes lacked clinical indications for skilled nursing care.
      In contrast, higher rates of medical conditions among nonelderly adults with
      depression underscored the need for integrated psychiatric and medical care in
      nursing homes.

PMID- 21885593
TI  - Sleep problems, psychiatric hospitalization, and emergency department use among
      psychiatric patients with Medicaid.
AB  - OBJECTIVE: This study examined the prevalence of sleep problems and their
      association with the use of inpatient and emergency department services by
      Medicaid recipients with serious mental illness. METHODS: The sample consisted of
      1,560 psychiatric patients with Medicaid coverage who were identified in a ten
      state random survey of psychiatrists. Sleep problems were assessed by clinician
      ratings. RESULTS: Over 75% of the patients experienced a sleep problem, and
      approximately 50% of these patients had problems that were moderate to severe.
      Greater sleep problem severity was associated with an increased risk of
      psychiatric hospitalization and emergency department visits for mental health
      reasons. CONCLUSIONS: Sleep problems were highly prevalent among Medicaid
      patients with serious mental illness and were associated with greater inpatient
      and emergency mental health service use. More careful monitoring and management
      of sleep problems in this patient population could address a common clinical need
      and might help to reduce costly service use.

PMID- 21885595
TI  - Creating barriers to mental health care in the Netherlands.

PMID- 21885596
TI  - A new blood-based diagnostic aid for schizophrenia.

PMID- 21885600
TI  - Cervical carotid artery disease in sickle cell anemia: clinical and radiological
      features.
AB  - Cervical internal carotid artery (cICA) occlusion is a recognized cause of acute
      ischemic stroke (AIS) in sickle cell disease (SCD), but the associated clinical
      and radiologic features are not well described. We reviewed data on cervical
      magnetic resonance angiography (cMRA) performed prospectively in 67 patients (55
      children) for indications including transcranial Doppler (TCD) abnormalities,
      AIS, or previous AIS. cICA lesions were seen in 10 (15%) patients, including 4 of
      7 patients presenting with AIS, and appear to have been missed on first
      presentation in 4 of 10 patients with previous AIS. Radiologic features in 7
      patients were consistent with dissection. In 2 patients, there was strong
      clinical and radiologic evidence for thromboembolic AIS, and this was also
      considered possible in 4 other patients. Three of the 4 AIS patients were
      anticoagulated acutely, and the nontreated patient had recurrent, probably
      thromboembolic, AIS. TCD findings were variable, but in 4 patients there were
      high velocities in the cerebral vessels contralateral to the cICA stenosis. We
      suggest that all patients with AIS should have cMRA during acute evaluation to
      identify cICA occlusions that may require anticoagulation. Routine screening of
      children with SCD should also include evaluation of neck vessels by carotid
      Doppler followed by cMRA if a cervical vascular lesion is suspected.

PMID- 21885599
TI  - Proof of principle for transfusion of in vitro-generated red blood cells.
AB  - In vitro RBC production from stem cells could represent an alternative to classic
      transfusion products. Until now the clinical feasibility of this concept has not
      been demonstrated. We addressed the question of the capacity of cultured RBCs
      (cRBCs) to survive in humans. By using a culture protocol permitting erythroid
      differentiation from peripheral CD34(+) HSC, we generated a homogeneous
      population of cRBC functional in terms of their deformability, enzyme content,
      capacity of their hemoglobin to fix/release oxygen, and expression of blood group
      antigens. We then demonstrated in the nonobese diabetes/severe combined
      immunodeficiency mouse that cRBC encountered in vivo the conditions necessary for
      their complete maturation. These data provided the rationale for injecting into
      one human a homogeneous sample of 10(10) cRBCs generated under good manufacturing
      practice conditions and labeled with (51)Cr. The level of these cells in the
      circulation 26 days after injection was between 41% and 63%, which compares
      favorably with the reported half-life of 28 +/- 2 days for native RBCs. Their
      survival in vivo testifies globally to their quality and functionality. These
      data establish the proof of principle for transfusion of in vitro-generated RBCs
      and path the way toward new developments in transfusion medicine. This study is
      registered at http://www.clinicaltrials.gov as NCT0929266.

PMID- 21885598
TI  - Integrins in cell migration.
AB  - Integrin-based adhesion has served as a model for studying the central role of
      adhesion in migration. In this article, we outline modes of migration, both
      integrin-dependent and -independent in vitro and in vivo. We next discuss the
      roles of adhesion contacts as signaling centers and linkages between the ECM and
      actin that allows adhesions to serve as traction sites. This includes signaling
      complexes that regulate migration and the interplay among adhesion, signaling,
      and pliability of the substratum. Finally, we address mechanisms of adhesion
      assembly and disassembly and the role of adhesion in cellular polarity.

PMID- 21885603
TI  - A stressed niche not Wnted.

PMID- 21885602
TI  - A survey of 90 patients with autoimmune lymphoproliferative syndrome related to
      TNFRSF6 mutation.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) is a genetic disorder
      characterized by early-onset, chronic, nonmalignant lymphoproliferation,
      autoimmune manifestations, and susceptibility to lymphoma. The majority of ALPS
      patients carry heterozygous germline (ALPS-FAS) or somatic mutations (ALPS-sFAS)
      of the TNFRSF6 gene coding for FAS. Although the clinical features of ALPS have
      been described previously, long-term follow-up data on morbidity and mortality
      are scarce. We performed a retrospective analysis of clinical and genetic
      features of 90 ALPS-FAS and ALPS-sFAS patients monitored over a median period of
      20.5 years. Heterozygous germline mutations of TNFRSF6 were identified in 83% of
      probands. Somatic TNFRSF6 mutations were found in 17% of index cases (all located
      within the intracellular domain of FAS). Sixty percent of the ALPS-FAS patients
      with mutations in the extracellular domain had a somatic mutation affecting the
      second allele of TNFRSF6; age at onset was later in these patients. No other
      genotype-phenotype correlations could be found. Long-term analysis confirmed a
      trend toward spontaneous remission of lymphoproliferation in adulthood but mixed
      outcomes for autoimmune manifestations. We observed significant and potentially
      life-threatening disease and treatment-related morbidity, including a high risk
      of sepsis after splenectomy that calls for careful long-term monitoring of ALPS
      patients. We also noted a significantly greater occurrence of disease-related
      symptoms in male than in female patients.

PMID- 21885601
TI  - How I treat autoimmune lymphoproliferative syndrome.
AB  - Autoimmune lymphoproliferative syndrome (ALPS) represents a failure of apoptotic
      mechanisms to maintain lymphocyte homeostasis, permitting accumulation of
      lymphoid mass and persistence of autoreactive cells that often manifest in
      childhood with chronic nonmalignant lymphadenopathy, hepatosplenomegaly, and
      recurring multilineage cytopenias. Cytopenias in these patients can be the result
      of splenic sequestration as well as autoimmune complications manifesting as
      autoimmune hemolytic anemia, immune-mediated thrombocytopenia, and autoimmune
      neutropenia. More than 300 families with hereditary ALPS have now been described;
      nearly 500 patients from these families have been studied and followed worldwide
      over the last 20 years by our colleagues and ourselves. Some of these patients
      with FAS mutations affecting the intracellular portion of the FAS protein also
      have an increased risk of B-cell lymphoma. The best approaches to diagnosis,
      follow-up, and management of ALPS, its associated cytopenias, and other
      complications resulting from infiltrative lymphoproliferation and autoimmunity
      are presented.

PMID- 21885605
TI  - Stress hematopoiesis requires Erg.

PMID- 21885604
TI  - RIC alloSCT in MM: a long way to go.

PMID- 21885606
TI  - Medullary interplay for central tolerance.

PMID- 21885607
TI  - Buzz in the dendritic cell synapse.

PMID- 21885608
TI  - Clots vs bugs: who's ahead?

PMID- 21885609
TI  - FISHing for aneuploidy in HSCT donors.

PMID- 21885610
TI  - Back to the OR?

PMID- 21885611
TI  - Polymorphism in the PAI-1 (SERPINE1) gene and the risk of osteonecrosis in
      children with acute lymphoblastic leukemia.

PMID- 21885612
TI  - Confocal imaging studies cast doubt on nuclear localization of JAK2V617F.

PMID- 21885613
TI  - Factor X binding to endothelial cell protein C receptor: comparison with factor
      VIIa and activated protein C.

PMID- 21885614
TI  - Linking air pollution exposure with thrombosis.

PMID- 21885615
TI  - Prediction of fetal status in fetal/neonatal alloimmune thrombocytopenia (FNAIT)?

PMID- 21885616
TI  - The pathophysiology of FNAIT cannot be deduced from highly selected retrospective
      data.

PMID- 21885617
TI  - Homozygosity mapping and targeted genomic sequencing reveal the gene responsible
      for cerebellar hypoplasia and quadrupedal locomotion in a consanguineous kindred.
AB  - The biological basis for the development of the cerebro-cerebellar structures
      required for posture and gait in humans is poorly understood. We investigated a
      large consanguineous family from Turkey exhibiting an extremely rare phenotype
      associated with quadrupedal locomotion, mental retardation, and cerebro
      cerebellar hypoplasia, linked to a 7.1-Mb region of homozygosity on chromosome
      17p13.1-13.3. Diffusion weighted imaging and fiber tractography of the patients'
      brains revealed morphological abnormalities in the cerebellum and corpus
      callosum, in particular atrophy of superior, middle, and inferior peduncles of
      the cerebellum. Structural magnetic resonance imaging showed additional
      morphometric abnormalities in several cortical areas, including the corpus
      callosum, precentral gyrus, and Brodmann areas BA6, BA44, and BA45. Targeted
      sequencing of the entire homozygous region in three affected individuals and two
      obligate carriers uncovered a private missense mutation, WDR81 p.P856L, which
      cosegregated with the condition in the extended family. The mutation lies in a
      highly conserved region of WDR81, flanked by an N-terminal BEACH domain and C
      terminal WD40 beta-propeller domains. WDR81 is predicted to be a transmembrane
      protein. It is highly expressed in the cerebellum and corpus callosum, in
      particular in the Purkinje cell layer of the cerebellum. WDR81 represents the
      third gene, after VLDLR and CA8, implicated in quadrupedal locomotion in humans.

PMID- 21885618
TI  - Contractions of the mouse prostate elicited by acetylcholine are mediated by M(3)
      muscarinic receptors.
AB  - Increased smooth muscle tone in the human prostate contributes to the symptoms
      associated with benign prostatic hyperplasia. In the mouse prostate gland,
      cholinergic innervation is responsible for a component of the nerve-mediated
      contractile response. This study investigates the muscarinic receptor subtype
      responsible for the cholinergic contractile response in the mouse prostate gland.
      To characterize the muscarinic receptor subtype, mouse prostates taken from wild
      type or M(3) muscarinic receptor knockout mice were mounted in organ baths. The
      isometric force that tissues developed in response to electrical-field
      stimulation or exogenously applied cholinergic agonists in the presence or
      absence of a range of muscarinic receptor antagonists was evaluated. Carbachol
      elicited reproducible and concentration-dependent contractions of the isolated
      mouse prostate, which were antagonized by the presence of muscarinic receptor
      antagonists. Calculation of antagonist affinities (pA(2) values) indicated a rank
      order of antagonist potencies in the mouse prostate of: darifenacin (9.08) =
      atropine (9.07) = 1,1-dimethyl-4-diphenylacetoxypiperidinium iodide (9.02) >
      cyclohexyl-hydroxy-phenyl-(3-piperidin-1-ylpropyl)silane (7.85) > cyclohexyl-(4
      fluorophenyl)-hydroxy-(3-piperidin-1-ylpropyl)silane (7.39) > himbacine (7.19) >
      pirenzipine (6.88) > methoctramine (6.20). Furthermore, genetic deletion of the
      M(3) muscarinic receptor inhibited prostatic contractions to electrical-field
      stimulation or exogenous administration of acetylcholine. In this study we
      identified that the cholinergic component of contraction in the mouse prostate is
      mediated by the M(3) muscarinic receptor subtype. Pharmacological antagonism of
      the M(3) muscarinic receptor may be a beneficial additional target for the
      treatment of benign prostatic hyperplasia in the human prostate gland.

PMID- 21885619
TI  - Indirect sympatholytic actions at beta-adrenoceptors account for the ocular
      hypotensive actions of cannabinoid receptor agonists.
AB  - Intraocular pressure (IOP) is the primary risk factor for glaucoma, a blinding
      eye disease. Cannabinoid agonists have long been known to decrease IOP,
      suggesting they may be useful in glaucoma treatment. However, the specific
      mechanism by which cannabinoids generate this ocular hypotensive effect remains
      unknown. The current evidence suggests the cannabinoids reduce IOP through
      actions at cannabinoid 1 (CB(1)) receptors within the eye, and adrenergic
      receptors (ARs) may also contribute to this action of cannabinoids. Considering
      this, the present study aimed to elucidate the mechanism behind the ocular
      hypotensive properties of cannabinoids through the use of mice genetically
      lacking either cannabinoid receptors or betaARs. Cannabinoid agonists, betaAR
      antagonists, and betaAR agonists decreased IOP in wild-type mice and CB(2)(-/-)
      mice. In contrast, none of these compounds were found to reduce IOP in betaAR(-/
      ) or CB(1)(-/-) mice. Desensitization of the betaARs and depletion of
      catecholamines in wild-type mice also eliminated the ability of the cannabinoid
      agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]
      1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate (WIN 55,212-2) to reduce
      IOP, strongly implicating a role for both betaARs and catecholamines in the
      ocular hypotensive properties of cannabinoids. Finally, CB(1) receptors were
      shown to colocalize with tyrosine hydroxylase, a marker for adrenergic neurons.
      Taken together, these findings suggest that betaARs are required for the ocular
      hypotensive properties of cannabinoids, and cannabinoids reduce IOP by acting as
      indirect sympatholytics and inhibiting norepinephrine release within the eye.

PMID- 21885622
TI  - Preferential hyperacuity perimeter as a functional tool for monitoring exudative
      age-related macular degeneration in patients treated by intravitreal ranibizumab.
AB  - PURPOSE: To analyze the response to anti vascular endothelial growth factor
      (VEGF) treatment for exudative age-related macular degeneration (AMD), with
      respect to changes in the Preferential Hyperacuity Perimeter (PHP), best
      corrected visual acuity (BCVA), and spectral-domain optical coherence tomography
      (SD-OCT), and to investigate whether the PHP score predicts the need for
      reinjection. METHODS: Consecutive patients with newly diagnosed exudative AMD
      underwent the PHP metamorphopsia test, BCVA, and SD-OCT at five time points after
      initiation of ranibizumab therapy (0.05 mL/0.5 mg). At the third and sixth
      months, reevaluation for additional injections was done. The relationships
      between PHP, BCVA, and SD-OCT parameters over time as well as their ability to
      predict the need for reinjection were examined. RESULTS: Analysis included 17
      eyes (17 patients, 70% females; mean age, 83.2 years). The mean PHP
      metamorphopsia test score improved from 25.6 +/- 41 (baseline) to 10.7 +/- 20.1
      (P < 0.05) over 6 months, after a mean of 4.2 (+/-1.0) injections. Mean reduction
      in SD-OCT parameters well reflected the functional improvements as evaluated by
      PHP (Spearman correlation = 0.9, P < 0.05). Mean BCVA did not improve over 6
      months (0.6 vs. 0.58 logMAR), and neither correlated with SD-OCT morphologic
      changes (Spearman correlation = 0.1, P > 0.05) nor with PHP functional changes
      (Spearman correlation = 0.1, P > 0.05). The PHP predicted the need for
      reinjection with an accuracy of 75% (sensitivity, 83 +/- 12%; specificity, 67 +/-
      15%), whereas a combination of all the measurements (PHP, BCVA, and SD-OCT)
      yielded an accuracy of 87% (sensitivity, 83 +/- 12%; specificity, 90 +/- 10%).
      CONCLUSIONS: Improvement in the metamorphopsia test score after intravitreal
      injections of ranibizumab, as well as its ability to predict the need for
      retreatment, suggest that PHP may be used to monitor response to anti-VEGF
      therapy in patients with exudative AMD.

PMID- 21885620
TI  - Investigation of the molecular mechanism of the alpha7 nicotinic acetylcholine
      receptor positive allosteric modulator PNU-120596 provides evidence for two
      distinct desensitized states.
AB  - Although alpha7 nicotinic acetylcholine receptors are considered potentially
      important therapeutic targets, the development of selective agonists has been
      stymied by the alpha7 receptor's intrinsically low probability of opening
      (P(open)) and the concern that an agonist-based therapeutic approach would
      disrupt endogenous cholinergic function. Development of alpha7 positive
      allosteric modulators (PAMs) holds promise of avoiding both issues. N-(5-Chloro
      2,4-dimethoxyphenyl)-N'-(5-methyl-3-isoxazolyl)-urea (PNU-120596) is one of the
      most effective alpha7 PAMs, with a mechanism associated, at least in part, with
      the destabilization of desensitized states. We studied the mechanism of PNU
      120596 potentiation of alpha7 receptors expressed in Xenopus laevis oocytes and
      outside-out patches from BOSC 23 cells. We identify two forms of alpha7
      desensitization: one is destabilized by PNU-120596 (D(s)), and the other is
      induced by strong episodes of activation and is stable in the presence of the PAM
      (D(i)). Our characterization of prolonged bursts of single-channel currents that
      occur with PNU-120596 provide a remarkable contrast to the behavior of the
      channels in the absence of the PAM. Individual channels that avoid the D(i) state
      show a 100,000-fold increase in P(open) compared with receptors in the
      nonpotentiated state. In the presence of PNU-120596, balance between D(s) and
      D(i) is dynamically regulated by both agonist and PAM binding, with maximal ion
      channel activity at intermediate levels of binding to both classes of sites. In
      the presence of high agonist concentrations, competitive antagonists may have the
      effect of shifting the balance in favor of D(s) and increasing ion channel
      currents.

PMID- 21885623
TI  - Direct-to-consumer genetic testing: reliable or risky?

PMID- 21885621
TI  - The ability of bacterial cocaine esterase to hydrolyze cocaine metabolites and
      their simultaneous quantification using high-performance liquid chromatography
      tandem mass spectrometry.
AB  - Cocaine toxicity is a widespread problem in the United States, responsible for
      more than 500,000 emergency department visits a year. There is currently no U.S.
      Food and Drug Administration-approved pharmacotherapy to directly treat cocaine
      toxicity. To this end, we have developed a mutant bacterial cocaine esterase (DM
      CocE), which has been previously shown to rapidly hydrolyze cocaine into inert
      metabolites, preventing and reversing toxicity with limited immunogenic
      potential. Herein we describe the ability of DM-CocE to hydrolyze the active
      cocaine metabolites norcocaine and cocaethylene and its inability to hydrolyze
      benzoylecgonine. DM-CocE hydrolyzes norcocaine and cocaethylene with 58 and 45%
      of its catalytic efficiency for cocaine in vitro as measured by a
      spectrophotometric assay. We have developed a mass spectrometry method to
      simultaneously detect cocaine, benzoylecgonine, norcocaine, and ecgonine methyl
      ester to quantify the effect of DM-CocE on normal cocaine metabolism in vivo. DM
      CocE administered to rats 10 min after a convulsant dose of cocaine alters the
      normal metabolism of cocaine, rapidly decreasing circulating levels of cocaine
      and norcocaine while increasing ecgonine methyl ester formation. Benzoylecgonine
      was not hydrolyzed in vivo, but circulating concentrations were reduced,
      suggesting that DM-CocE may bind and sequester this metabolite. These findings
      suggest that DM-CocE may reduce cocaine toxicity by eliminating active and toxic
      metabolites along with the parent cocaine molecule.

PMID- 21885624
TI  - Evolution of dyspnea during exercise in chronic obstructive pulmonary disease:
      impact of critical volume constraints.
AB  - RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) primarily
      describe their exertional dyspnea using descriptors alluding to increased effort
      or work of breathing and unsatisfied inspiration or inspiratory difficulty.
      OBJECTIVES: The purpose of this study was to examine the impact of changes in
      dynamic respiratory mechanics during incremental (INCR) and high-intensity
      constant work-rate (CWR) cycle exercise on the evolution of dyspnea intensity and
      its major qualitative dimensions in patients with moderate-to-severe COPD.
      METHODS: Sixteen subjects with COPD performed symptom-limited INCR and CWR cycle
      exercise tests. Measurements included dyspnea intensity and qualitative
      descriptors, breathing pattern, operating lung volumes, and esophageal pressure
      (Pes). MEASUREMENTS AND MAIN RESULTS: During both exercise tests, there was an
      inflection in the relation between tidal volume (Vt) and ventilation. This
      inflection occurred significantly earlier in time during CWR versus INCR exercise
      but at a similar ventilation, Vt, and tidal Pes swing. Beyond this inflection,
      there was no further change in Vt despite a continued increase in ventilation and
      tidal Pes. During both tests, "work and effort" was the dominant dyspnea
      descriptor selected up to the inflection point, whereas after this point dyspnea
      intensity and the selection frequency of "unsatisfied inspiration" rose sharply.
      CONCLUSIONS: Regardless of the exercise test protocol, the inflection (or
      plateau) in the Vt response marked the point where dyspnea intensity rose
      abruptly and there was a transition in the dominant qualitative descriptor choice
      from "work and effort" to "unsatisfied inspiration." Intensity and quality of
      dyspnea evolve separately and are strongly influenced by mechanical constraints
      on Vt expansion during exercise in COPD.

PMID- 21885627
TI  - Linking payment to quality: opportunities and challenges for critical care.

PMID- 21885626
TI  - Telomere dysfunction causes sustained inflammation in chronic obstructive
      pulmonary disease.
AB  - RATIONALE: Chronic obstructive pulmonary disease (COPD) is associated with
      chronic inflammation of unknown pathogenesis. OBJECTIVES: To investigate whether
      telomere dysfunction and senescence of pulmonary vascular endothelial cells (P
      ECs) induce inflammation in COPD. METHODS: Prospective comparison of patients
      with COPD and age- and sex-matched control smokers. Investigation of mice null
      for telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc)
      genes. MEASUREMENTS AND MAIN RESULTS: In situ lung specimen studies showed a
      higher percentage of senescent P-ECs stained for p16 and p21 in patients with
      COPD than in control subjects. Cultured P-ECs from patients with COPD exhibited
      early replicative senescence, with decreased cell-population doublings, a higher
      percentage of beta-galactosidase-positive cells, reduced telomerase activity,
      shorter telomeres, and higher p16 and p21 mRNA levels at an early cell passage
      compared with control subjects. Senescent P-ECs released cytokines and mediators:
      the levels of IL-6, IL-8, monocyte chemotactic protein (MCP)-1, Hu-GRO, and
      soluble intercellular adhesion molecule (sICAM)-1 were elevated in the media of P
      ECs from patients compared with control subjects at an early cell passage, in
      proportion to the senescent P-EC increase and telomere shortening. Up-regulation
      of MCP-1 and sICAM-1 led to increased monocyte adherence and migration. The
      elevated MCP-1, IL-8, Hu-GROalpha, and ICAM-1 levels measured in lungs from
      patients compared with control subjects correlated with P-EC senescence criteria
      and telomere length. In Tert(-/-) and/or Terc(-/-) mouse lungs, levels of the
      corresponding cytokines (MCP-1, IL-8, Hu-GROalpha, and ICAM-1) were also altered,
      despite the absence of external stimuli and in proportion to telomere
      dysfunction. CONCLUSIONS: Telomere dysfunction and premature P-EC senescence are
      major processes perpetuating lung inflammation in COPD.

PMID- 21885628
TI  - Clinic practice guidelines: more of the same?

PMID- 21885625
TI  - Impact of race on asthma treatment failures in the asthma clinical research
      network.
AB  - RATIONALE: Recent studies suggest that people with asthma of different racial
      backgrounds may respond differently to various therapies. OBJECTIVES: To use data
      from well-characterized participants in prior Asthma Clinical Research Network
      (ACRN) trials to determine whether racial differences affected asthma treatment
      failures. METHODS: We analyzed baseline phenotypes and treatment failure rates
      (worsening asthma resulting in systemic corticosteroid use, hospitalization,
      emergency department visit, prolonged decrease in peak expiratory flow, increase
      in albuterol use, or safety concerns) in subjects participating in 10 ACRN trials
      (1993-2003). Self-declared race was reported in each trial and treatment failure
      rates were stratified by race. MEASUREMENTS AND MAIN RESULTS: A total of 1,200
      unique subjects (whites = 795 [66%]; African Americans = 233 [19%]; others = 172
      [14%]; mean age = 32) were included in the analyses. At baseline, African
      Americans had fewer asthma symptoms (P < 0.001) and less average daily rescue
      inhaler use (P = 0.007) than whites. There were no differences in baseline FEV(1)
      (% predicted); asthma quality of life; bronchial hyperreactivity; or exhaled
      nitric oxide concentrations. A total of 147 treatment failures were observed; a
      significantly higher proportion of African Americans (19.7%; n = 46) experienced
      a treatment failure compared with whites (12.7%; n = 101) (odds ratio = 1.7; 95%
      confidence interval, 1.2-2.5; P = 0.007). When stratified by treatment, African
      Americans receiving long-acting beta-agonists were twice as likely as whites to
      experience a treatment failure (odds ratio = 2.1; 95% confidence interval, 1.3
      3.6; P = 0.004), even when used with other controller therapies. CONCLUSIONS:
      Despite having fewer asthma symptoms and less rescue beta-agonist use, African
      Americans with asthma have more treatment failures compared with whites,
      especially when taking long-acting beta-agonists.

PMID- 21885629
TI  - FEV1 in the suburbs: choose your research subjects wisely.

PMID- 21885630
TI  - Targeting elastase in bronchopulmonary dysplasia.

PMID- 21885631
TI  - The lung macrophage: a Jack of all trades.

PMID- 21885632
TI  - Will the small airways rise again?

PMID- 21885633
TI  - Caveat emptor? Control of latent tuberculosis infection in the United States.

PMID- 21885634
TI  - Pro: beta-agonists in acute lung injury--the end of the story?

PMID- 21885635
TI  - Con: beta2-adrenergic agonists in ALI/ARDS--not recommended or potentially
      harmful?

PMID- 21885637
TI  - Recommended reading from the university of british columbia respiratory fellows
      and critical care fellows: respiratory fellowship program director: frank ryan;
      critical care fellowship program director: george isac.

PMID- 21885636
TI  - An official ATS clinical practice guideline: interpretation of exhaled nitric
      oxide levels (FENO) for clinical applications.
AB  - BACKGROUND: Measurement of fractional nitric oxide (NO) concentration in exhaled
      breath (Fe(NO)) is a quantitative, noninvasive, simple, and safe method of
      measuring airway inflammation that provides a complementary tool to other ways of
      assessing airways disease, including asthma. While Fe(NO) measurement has been
      standardized, there is currently no reference guideline for practicing health
      care providers to guide them in the appropriate use and interpretation of Fe(NO)
      in clinical practice. PURPOSE: To develop evidence-based guidelines for the
      interpretation of Fe(NO) measurements that incorporate evidence that has
      accumulated over the past decade. METHODS: We created a multidisciplinary
      committee with expertise in the clinical care, clinical science, or basic science
      of airway disease and/or NO. The committee identified important clinical
      questions, synthesized the evidence, and formulated recommendations.
      Recommendations were developed using pragmatic systematic reviews of the
      literature and the GRADE approach. RESULTS: The evidence related to the use of
      Fe(NO) measurements is reviewed and clinical practice recommendations are
      provided. CONCLUSIONS: In the setting of chronic inflammatory airway disease
      including asthma, conventional tests such as FEV(1) reversibility or provocation
      tests are only indirectly associated with airway inflammation. Fe(NO) offers
      added advantages for patient care including, but not limited to (1) detecting of
      eosinophilic airway inflammation, (2) determining the likelihood of
      corticosteroid responsiveness, (3) monitoring of airway inflammation to determine
      the potential need for corticosteroid, and (4) unmasking of otherwise unsuspected
      nonadherence to corticosteroid therapy.

PMID- 21885638
TI  - Pulmonary arteriovenous malformation.

PMID- 21885639
TI  - Diesel motor exhaust and lung cancer: additional perspectives.

PMID- 21885641
TI  - Vitamin C and Community-acquired Pneumonia.

PMID- 21885640
TI  - Shock and pulmonary edema secondary to severe acute hypercapnic acidosis.

PMID- 21885643
TI  - Introduction: Pediatric obesity and the role of children's hospitals.

PMID- 21885644
TI  - Identification and treatment of obesity as a standard of care for all patients in
      children's hospitals.
AB  - Obese children and adolescents have unique needs for specialized medical
      equipment while hospitalized and might require special diets and physical
      activity options as part of their medical treatment. It is important that
      patients with a diagnosis of obesity be identified on admission so that
      appropriate equipment and resources can be provided. We examined what components
      a healthy hospital environment should include and sought to determine if
      children's hospitals provide a healthy hospital environment that offers these
      components. In addition, we sought to determine if children's hospitals have
      policies in place to identify children with obesity so that appropriate resources
      and services can be offered to treat that diagnosis. We surveyed National
      Association of Children's Hospitals and Related Institutions member hospitals via
      a Web-based questionnaire and found that the majority of them do not have
      policies in place to identify patients with obesity. We did find that the
      majority of hospitals reported innovative programs or services to provide a
      healthy hospital environment for their patients, visitors, and staff but
      acknowledged limitations in providing some services. Specifically, children's
      hospitals can and should improve on their identification and management of obese
      pediatric patients.

PMID- 21885645
TI  - Assessment of obese children and adolescents: a survey of pediatric obesity
      management programs.
AB  - This article provides descriptive information on the assessments conducted in
      stage 3 or 4 pediatric obesity-management programs associated with National
      Association of Children's Hospital and Related Institutions hospitals enrolled in
      FOCUS on a Fitter Future. Eighteen institutions completed a survey that
      considered the following assessments: patient/family medical history; physical
      examination; blood pressure; body size and composition; blood chemistry; aerobic
      fitness; resting metabolic rate; muscle strength and flexibility; gross motor
      function; spirometry; sedentary behavior and physical activity; dietary behavior
      and nutrition; and psychological assessments. Frequency distributions were
      determined for each question. Overall, the results indicate that most programs
      that participated in this survey were following 2007 Expert Committee assessment
      recommendations; however, a variety of measurement tools were used. The variation
      in assessment tools, protocols, etc is partially caused by the program diversity
      dictated by personnel, both in terms of number and duties. It also shows the
      challenges in standardizing methodologies across clinics if we hope to establish
      a national registry for pediatric obesity clinics. In addition to providing a
      better understanding of the current assessment practices in pediatric obesity
      management programs, the results provided herein should assist other
      clinics/hospitals that are developing pediatric obesity programs.

PMID- 21885646
TI  - Patient engagement and attrition in pediatric obesity clinics and programs:
      results and recommendations.
AB  - Pediatric tertiary care institutions are well positioned to provide
      multidisciplinary, intensive interventions for pediatric obesity known as stage 3
      treatment. One contributor to the difficulty in administering this treatment is
      the high rate of patient attrition. Little is known about the practices used by
      pediatric weight-management clinics and group-based programs to minimize
      attrition. Hospital members and nonmembers of FOCUS on a Fitter Future were
      surveyed on the methods used to engage and retain obese children in their clinics
      and programs. Shortly thereafter, a benchmarking activity that centered on rates
      of patient nonattendance at initial and follow-up clinic visits was initiated
      among FOCUS-group-participating hospitals. Clinic- and group-based program
      results were contrasted. Staff from group-based programs reported that the
      majority of patients did not complete even 50% of program follow-up visits.
      Multiple patient/family- and clinic/program-level barriers to retention were
      identified. Attention to successful techniques should be paid during planning for
      new programs and improvement of established ones.

PMID- 21885648
TI  - Building capacity for childhood obesity prevention and treatment in the medical
      community: call to action.
AB  - Large gaps exist in the capacity of the US medical system to participate
      meaningfully in childhood obesity-prevention efforts and to meet the treatment
      needs of obese children. Current primary care practice for the prevention and
      treatment of childhood obesity often varies from evidence-based recommendations.
      Childhood obesity specialists have partnered successfully with schools of
      medicine, professional societies, and other organizations to collaboratively
      engage with primary care providers in quality improvement for obesity prevention
      and treatment. This review and commentary targets 2 audiences. For childhood
      obesity experts and their organizational partners, methods to support change in
      primary practice and the evidence supporting their use are outlined. For primary
      care providers and non-obesity specialists, effective strategies for changing
      practice and the potential benefits of addressing childhood obesity
      systematically are discussed.

PMID- 21885647
TI  - Developing criteria for pediatric/adolescent bariatric surgery programs.
AB  - The prevalence of morbid obesity in adolescents is rising at an alarming rate.
      Comorbidities known to predispose to cardiovascular disease are increasingly
      being diagnosed in these children. Bariatric surgery has become an acceptable
      treatment alternative for morbidly obese adults, and criteria have been developed
      to establish center-of-excellence designation for adult bariatric surgery
      programs. Evidence suggests that bariatric surgical procedures are being
      performed with increasing numbers in adolescents. We have examined and compiled
      the current expert recommendations for guidelines and criteria that are needed to
      deliver safe and effective bariatric surgical care to adolescents.

PMID- 21885649
TI  - Payment for obesity services: examples and recommendations for stage 3
      comprehensive multidisciplinary intervention programs for children and
      adolescents.
AB  - OBJECTIVE: The Reimbursement and Payment Subcommittee of the National Association
      of Children's Hospitals and Related Institutions FOCUS on a Fitter Future group
      sought to guide medical providers, patients, and payers to better serve obese
      children and adolescents to enable optimum health. Recommendations are provided
      for the essential components of a stage 3 comprehensive multidisciplinary
      intervention program as defined by the 2007 Expert Committee recommendations. In
      addition, suggestions are offered for a stepwise approach to implement these
      recommendations. METHODS: In 2009, key informant interviews were conducted with
      15 children's hospitals participating in FOCUS on a Fitter Future and 1
      nonparticipating hospital. Interview transcripts identified 5 financially
      sustainable stage 3 programs, each funded differently. RESULTS: The stage 3
      programs interviewed ranged from being nascent to 21 years old (27%, <2 years;
      47%, 2-6 years; 27%, >6 years). All of them had multidisciplinary teams that
      delivered services through 1 of 3 institutional structures: 60% freestanding; 7%
      specialty; and 33% hospital within a hospital. One-third of them had 1 to 2
      funding sources, and 67% had >= 3 sources. CONCLUSIONS: The stage 3 programs in
      this review shared some common strategies for achieving financial stability. All
      of them followed key strategies of the chronic care model, the details of which
      led to the following recommendation: stage 3 programs should include a health
      care team with a medical provider, registered dietitian, physical activity
      specialist, mental health specialist, and coordinator who, as a team, provide
      service to overweight and obese children at no less than moderate intensity (26
      75 hours).

PMID- 21885650
TI  - Perspectives on obesity programs at children's hospitals: insights from senior
      program administrators.
AB  - OBJECTIVE: The obesity epidemic has resulted in an increasing number of children
      needing multidisciplinary obesity treatment. To meet this need, pediatric obesity
      programs have arisen, particularly in children's hospitals. In 2008, the National
      Association of Children's Hospitals and Related Institutions (NACHRI) convened
      FOCUS on a Fitter Future, a group drawn from NACHRI member institutions, to
      investigate the needs, barriers, and capacity-building in these programs.
      METHODS: Senior administrators of the 47 NACHRI member hospitals that completed
      an application to participate in the FOCUS group were invited to complete a Web
      based survey. The survey targeted 4 key areas: (1) perceived value of the obesity
      program; (2) funding mechanisms; (3) administrative challenges; and (4)
      sustainability of the programs. RESULTS: Nearly three-quarters of the respondents
      reported that their obesity programs were integrated into their hospitals'
      strategic plans. Obesity programs added value to their institutions because the
      programs met the needs of patients and families (97%), met the needs of health
      care providers (91%), prevented future health problems in children (85%), and
      increased visibility in the community (79%). Lack of reimbursement (82%) and high
      operating costs (71%) were the most frequently cited challenges. Respondents most
      frequently identified demonstration of program effectiveness (79%) as a factor
      that is necessary for ensuring program sustainability. CONCLUSIONS: Hospital
      administrators view tackling childhood obesity as integral to their mission to
      care for children. Our results serve to inform hospital clinicians and
      administrators as they develop and implement sustainable pediatric obesity
      programs.

PMID- 21885651
TI  - Expression and regulation of Homer in human skeletal muscle during neuromuscular
      junction adaptation to disuse and exercise.
AB  - Protein calcium sensors of the Homer family have been proposed to modulate the
      activity of various ion channels and nuclear factor of activated T cells (NFAT),
      the transcription factor modulating skeletal muscle differentiation. We monitored
      Homer expression and subcellular localization in human skeletal muscle biopsies
      following 60 d of bedrest [Second Berlin Bedrest Study (BBR2-2)]. Soleus (SOL)
      and vastus lateralis (VL) biopsies were taken at start (pre) and at end (end) of
      bedrest from healthy male volunteers of a control group without exercise (CTR;
      n=9), a resistive-only exercise group (RE; n=7), and a combined
      resistive/vibration exercise group (RVE; n=7). Confocal analysis showed Homer
      immunoreactivity at the postsynaptic microdomain of the neuromuscular junction
      (NMJ) at bedrest start. After bedrest, Homer immunoreactivity decreased (CTR),
      remained unchanged (RE), or increased (RVE) at the NMJ. Homer2 mRNA and protein
      were differently regulated in a muscle-specific way. Activated NFATc1
      translocates from cytoplasm to nucleus; increased amounts of NFATc1
      immunopositive slow-type myonuclei were found in RVE myofibers of both muscles.
      Pulldown assays identified NFATc1 and Homer as molecular partners in skeletal
      muscle. A direct motor nerve control of Homer2 was confirmed in rat NMJs by in
      vivo denervation. Homer2 is localized at the NMJ and is part of the calcineurin
      NFATc1 signaling pathway. RVE has additional benefit over RE as countermeasure
      preventing disuse-induced neuromuscular maladaptation during bedrest.

PMID- 21885652
TI  - The histaminergic system regulates wakefulness and orexin/hypocretin neuron
      development via histamine receptor H1 in zebrafish.
AB  - The histaminergic and hypocretin/orexin (hcrt) neurotransmitter systems play
      crucial roles in alertness/wakefulness in rodents. We elucidated the role of
      histamine in wakefulness and the interaction of the histamine and hcrt systems in
      larval zebrafish. Translation inhibition of histidine decarboxylase (hdc) with
      morpholino oligonucleotides (MOs) led to a behaviorally measurable decline in
      light-associated activity, which was partially rescued by hdc mRNA injections and
      mimicked by histamine receptor H1 (Hrh1) antagonist pyrilamine treatment.
      Histamine-immunoreactive fibers targeted the dorsal telencephalon, an area that
      expresses histamine receptors hrh1 and hrh3 and contains predominantly
      glutamatergic neurons. Tract tracing with DiI revealed that projections from
      dorsal telencephalon innervate the hcrt and histaminergic neurons. Translation
      inhibition of hdc decreased the number of hcrt neurons in a Hrh1-dependent
      manner. The reduction was rescued by overexpression of hdc mRNA. hdc mRNA
      injection alone led to an up-regulation of hcrt neuron numbers. These results
      suggest that histamine is essential for the development of a functional and
      intact hcrt system and that histamine has a bidirectional effect on the
      development of the hcrt neurons. In summary, our findings provide evidence that
      these two systems are linked both functionally and developmentally, which may
      have important implications in sleep disorders and narcolepsy. development via
      histamine receptor H1 in zebrafish.

PMID- 21885654
TI  - Lipoxin A4 is a novel estrogen receptor modulator.
AB  - Inflammation is intimately linked with naturally occurring remodeling events in
      the endometrium. Lipoxins comprise a group of short-lived, nonclassic eicosanoids
      possessing potent anti-inflammatory and proresolution properties. In the present
      study, we investigated the role of lipoxin A(4) (LXA(4)) in the endometrium and
      demonstrated that 15-LOX-2, an enzyme necessary for LX biosynthesis, is expressed
      in this tissue. Our results establish that LXA(4) possesses robust estrogenic
      activity through its capacity to alter ERE transcriptional activity, as well as
      expression of estrogen-regulated genes, alkaline phosphatase activity, and
      proliferation in human endometrial epithelial cells. Interestingly, LXA(4) also
      demonstrated antiestrogenic potential, significantly attenuating E2-induced
      activity. This estrogenic activity was directly mediated through estrogen
      receptors (ERs). Subsequent investigations determined that the actions of LXA(4)
      are exclusively mediated through ERalpha and closely mimic those of the potent
      estrogen 17beta-estradiol (E2). In binding assays, LXA(4) competed with E2 for ER
      binding, with an IC(50) of 46 nM. Furthermore, LXA(4) exhibited estrogenic
      activity in vivo, increasing uterine wet weight and modulating E2-regulated gene
      expression. These findings reveal a previously unappreciated facet of LXA(4)
      bioactions, implicating this lipid mediator in novel immunoendocrine crosstalk
      mechanisms.

PMID- 21885653
TI  - Structural and functional aspects of the myosin essential light chain in cardiac
      muscle contraction.
AB  - The myosin essential light chain (ELC) is a structural component of the
      actomyosin cross-bridge, but its function is poorly understood, especially the
      role of the cardiac specific N-terminal extension in modulating actomyosin
      interaction. Here, we generated transgenic (Tg) mice expressing the A57G (alanine
      to glycine) mutation in the cardiac ELC known to cause familial hypertrophic
      cardiomyopathy (FHC). The function of the ELC N-terminal extension was
      investigated with the Tg-Delta43 mouse model, whose myocardium expresses a
      truncated ELC. Low-angle X-ray diffraction studies on papillary muscle fibers in
      rigor revealed a decreased interfilament spacing (~ 1.5 nm) and no alterations in
      cross-bridge mass distribution in Tg-A57G mice compared to Tg-WT, expressing the
      full-length nonmutated ELC. The truncation mutation showed a 1.3-fold increase in
      I(1,1)/I(1,0), indicating a shift of cross-bridge mass from the thick filament
      backbone toward the thin filaments. Mechanical studies demonstrated increased
      stiffness in Tg-A57G muscle fibers compared to Tg-WT or Tg-Delta43. The
      equilibrium constant for the cross-bridge force generation step was smallest in
      Tg-Delta43. These results support an important role for the N-terminal ELC
      extension in prepositioning the cross-bridge for optimal force production. Subtle
      changes in the ELC sequence were sufficient to alter cross-bridge properties and
      lead to pathological phenotypes.

PMID- 21885655
TI  - AMP-activated protein kinase enhances the phagocytic ability of macrophages and
      neutrophils.
AB  - Although AMPK plays well-established roles in the modulation of energy balance,
      recent studies have shown that AMPK activation has potent anti-inflammatory
      effects. In the present experiments, we examined the role of AMPK in
      phagocytosis. We found that ingestion of Escherichia coli or apoptotic cells by
      macrophages increased AMPK activity. AMPK activation increased the ability of
      neutrophils or macrophages to ingest bacteria (by 46 +/- 7.8 or 85 +/- 26%,
      respectively, compared to control, P<0.05) and the ability of macrophages to
      ingest apoptotic cells (by 21 +/- 1.4%, P<0.05 compared to control). AMPK
      activation resulted in cytoskeletal reorganization, including enhanced formation
      of actin and microtubule networks. Activation of PAK1/2 and WAVE2, which are
      downstream effectors of Rac1, accompanied AMPK activation. AMPK activation also
      induced phosphorylation of CLIP-170, a protein that participates in microtubule
      synthesis. The increase in phagocytosis was reversible by the specific AMPK
      inhibitor compound C, siRNA to AMPKalpha1, Rac1 inhibitors, or agents that
      disrupt actin or microtubule networks. In vivo, AMPK activation resulted in
      enhanced phagocytosis of bacteria in the lungs by 75 +/- 5% vs. control (P<0.05).
      These results demonstrate a novel function for AMPK in enhancing the phagocytic
      activity of neutrophils and macrophages.

PMID- 21885656
TI  - Destabilization of the neuromuscular junction by proteolytic cleavage of agrin
      results in precocious sarcopenia.
AB  - Etiology and pathogenesis of sarcopenia, the progressive decline in skeletal
      muscle mass and strength that occurs with aging, are still poorly understood. We
      recently found that overexpression of the neural serine protease neurotrypsin in
      motoneurons resulted in the degeneration of their neuromuscular junctions (NMJ)
      within days. Therefore, we wondered whether neurotrypsin-dependent NMJ
      degeneration also affected the structure and function of the skeletal muscles.
      Using histological and functional analyses of neurotrypsin-overexpressing and
      neurotrypsin-deficient mice, we found that overexpression of neurotrypsin in
      motoneurons installed the full sarcopenia phenotype in young adult mice.
      Characteristic muscular alterations included a reduced number of muscle fibers,
      increased heterogeneity of fiber thickness, more centralized nuclei, fiber-type
      grouping, and an increased proportion of type I fibers. As in age-dependent
      sarcopenia, excessive fragmentation of the NMJ accompanied the muscular
      alterations. These results suggested the destabilization of the NMJ through
      proteolytic cleavage of agrin at the onset of a pathogenic pathway ending in
      sarcopenia. Studies of neurotrypsin-deficient and agrin-overexpressing mice
      revealed that old-age sarcopenia also develops without neurotrypsin and is not
      prevented by elevated levels of agrin. Our results define neurotrypsin- and age
      dependent sarcopenia as the common final outcome of 2 etiologically distinct
      entities.

PMID- 21885657
TI  - Pause and pulse: radiation dose in pediatric fluoroscopy.

PMID- 21885658
TI  - Ethics for the pediatrician: religion and spirituality in pediatrics.

PMID- 21885659
TI  - Obesity prevention and treatment.

PMID- 21885661
TI  - Epstein-Barr virus.

PMID- 21885662
TI  - Visual diagnosis: swelling of the left side of the neck in an adolescent.

PMID- 21885663
TI  - Index of suspicion. Case 1: round opacity on chest radiograph, cough, and fever
      in a child. Case 2: groin pain and limp in a 10-year-old. Case 3: focal
      neurologic signs in the presence of sickle cell disease. Case 4: hypoglycemia and
      microphallus in an infant.

PMID- 21885664
TI  - Scoliosis.

PMID- 21885665
TI  - Thrombocytopenia absent radius syndrome.

PMID- 21885666
TI  - Inherited hematologic and oncologic syndromes.

PMID- 21885667
TI  - Growth.

PMID- 21885668
TI  - Tomato SlSnRK1 protein interacts with and phosphorylates betaC1, a pathogenesis
      protein encoded by a geminivirus beta-satellite.
AB  - The betaC1 protein of tomato yellow leaf curl China beta-satellite functions as a
      pathogenicity determinant. To better understand the molecular basis of betaC1 in
      pathogenicity, a yeast two-hybrid screen of a tomato (Solanum lycopersicum) cDNA
      library was carried out using betaC1 as bait. betaC1 interacted with a tomato
      SUCROSE-NONFERMENTING1-related kinase designated as SlSnRK1. Their interaction
      was confirmed using a bimolecular fluorescence complementation assay in Nicotiana
      benthamiana cells. Plants overexpressing SnRK1 were delayed for symptom
      appearance and contained lower levels of viral and satellite DNA, while plants
      silenced for SnRK1 expression developed symptoms earlier and accumulated higher
      levels of viral DNA. In vitro kinase assays showed that betaC1 is phosphorylated
      by SlSnRK1 mainly on serine at position 33 and threonine at position 78. Plants
      infected with betaC1 mutants containing phosphorylation-mimic aspartate residues
      in place of serine-33 and/or threonine-78 displayed delayed and attenuated
      symptoms and accumulated lower levels of viral DNA, while plants infected with
      phosphorylation-negative alanine mutants contained higher levels of viral DNA.
      These results suggested that the SlSnRK1 protein attenuates geminivirus infection
      by interacting with and phosphorylating the betaC1 protein.

PMID- 21885669
TI  - Warfarin-related nephropathy modeled by nephron reduction and excessive
      anticoagulation.
AB  - An acute increase in international normalized ratio (INR) to >3.0 in patients
      with chronic kidney disease (CKD) can associate with an unexplained acute
      increase in serum creatinine and accelerated progression of CKD. A subset of
      these patients have renal tubular obstruction by casts of red blood cells,
      presumably the dominant mechanism of the acute kidney injury described as
      warfarin-related nephropathy. Here, we developed an animal model of this acute
      kidney injury that is based on the 5/6-nephrectomy model to aid future
      investigation of the pathogenesis of this condition. We found that acute
      excessive anticoagulation with brodifacoum ("superwarfarin") increased serum
      creatinine levels and hematuria in 5/6-nephrectomized rats but not in controls.
      In addition, morphologic findings in 5/6-nephrectomized rats included glomerular
      hemorrhage, occlusive red blood cell casts, and acute tubular injury, similar to
      the biopsy findings among affected patients. Furthermore, in the rat model, we
      observed an increase in apoptosis of glomerular endothelial cells. In summary,
      the 5/6-nephrectomy model combined with excessive anticoagulation may be a useful
      tool to study the pathogenesis of warfarin-related nephropathy.

PMID- 21885672
TI  - Evaluation of smoking prevention television messages based on the elaboration
      likelihood model.
AB  - Progress in reducing youth smoking may depend on developing improved methods to
      communicate with higher risk youth. This study explored the potential of smoking
      prevention messages based on the Elaboration Likelihood Model (ELM) to address
      these needs. Structured evaluations of 12 smoking prevention messages based on
      three strategies derived from the ELM were conducted in classroom settings among
      a diverse sample of non-smoking middle school students in three states (n =
      1771). Students categorized as likely to have higher involvement in a decision to
      initiate cigarette smoking reported relatively high ratings on a cognitive
      processing indicator for messages focused on factual arguments about negative
      consequences of smoking than for messages with fewer or no direct arguments.
      Message appeal ratings did not show greater preference for this message type
      among higher involved versus lower involved students. Ratings from students
      reporting lower academic achievement suggested difficulty processing factual
      information presented in these messages. The ELM may provide a useful strategy
      for reaching adolescents at risk for smoking initiation, but particular attention
      should be focused on lower academic achievers to ensure that messages are
      appropriate for them. This approach should be explored further before similar
      strategies could be recommended for large-scale implementation.

PMID- 21885670
TI  - Distinct roles of CSF-1 isoforms in lupus nephritis.
AB  - Colony-stimulating factor-1 (CSF-1), the principal growth factor for macrophages,
      is increased in the kidney, serum, and urine of patients with lupus nephritis,
      and eliminating CSF-1 suppresses lupus in MRL-Fas(lpr) mice. CSF-1 has three
      biologically active isoforms: a membrane-spanning cell surface glycoprotein
      (csCSF-1), a secreted proteoglycan (spCSF-1), and a secreted glycoprotein (sgCSF
      1); the role of each isoform in the circulation and kidney in autoimmune disease
      is not well understood. Here, we constructed mutant MRL-Fas(lpr) mice that only
      express csCSF-1 or precursors of the spCSF-1 and sgCSF-1 isoforms. Both csCSF-1
      and spCSF-1 shifted monocytes toward proinflammatory, activated populations,
      enhancing their recruitment into the kidney during lupus nephritis. With
      advancing lupus nephritis, spCSF-1 was the predominant isoform responsible for
      increasing circulating CSF-1 and, along with the csCSF-1 isoform, for increasing
      intrarenal CSF-1. Thus, csCSF-1 appears to initiate and promote the local
      activation of macrophages within the kidney. Intrarenal expression of csCSF-1 and
      spCSF-1 increases with advancing nephritis, thereby promoting the intrarenal
      recruitment of monocytes and expansion of Ly6C(hi) macrophages, which induce
      apoptosis of the renal parenchyma. Taken together, these data suggest that the
      three CSF-1 isoforms have distinct biologic properties, suggesting that blocking
      both circulating and intrarenal CSF-1 may be necessary for therapeutic efficacy.

PMID- 21885671
TI  - Astrocytes are an early target in osmotic demyelination syndrome.
AB  - Abrupt osmotic changes during rapid correction of chronic hyponatremia result in
      demyelinative brain lesions, but the sequence of events linking rapid osmotic
      changes to myelin loss is not yet understood. Here, in a rat model of osmotic
      demyelination syndrome, we found that massive astrocyte death occurred after
      rapid correction of hyponatremia, delineating the regions of future myelin loss.
      Astrocyte death caused a disruption of the astrocyte-oligodendrocyte network,
      rapidly upregulated inflammatory cytokines genes, and increased serum S100B,
      which predicted clinical manifestations and outcome of osmotic demyelination.
      These results support a model for the pathophysiology of osmotic brain injury in
      which rapid correction of hyponatremia triggers apoptosis in astrocytes followed
      by a loss of trophic communication between astrocytes and oligodendrocytes,
      secondary inflammation, microglial activation, and finally demyelination.

PMID- 21885673
TI  - The contribution of parent-child interactions to smoking experimentation in
      adolescence: implications for prevention.
AB  - Because few prospective studies have examined the independent influence of
      mothers and fathers on smoking experimentation, we tested the association between
      a set of parent-specific, familial and peer interactions with smoking
      experimentation in early adolescence. Data come from two cohorts in the British
      Youth Panel Survey (N = 1736; mean age at baseline, 11.26; SD = 0.65), a study of
      children resident with members of the British Household Panel Survey. Baseline
      data showed 8.2% of participants had smoked which increased to 40.3% after a 3
      year follow-up. Multivariate logistic regression models showed risk factors for
      the onset of experimentation included frequent time spent with peers (P < 0.001),
      maternal smoking (P = 0.001), female gender and older participant age (P <
      0.001). Parent-child quarrels, mother-child conversations, family meal frequency
      and household income were not significantly associated with experimentation.
      Frequent father-child conversations, about things which mattered to children,
      were the only type of parent-child contact associated with a reduced risk of
      experimentation (P < 0.001), and a significant interaction suggested that
      maternal smoking increased the likelihood of girls but not boys experimentation
      (P = 0.01). This study suggests that familial risk and protective factors operate
      independently and that more attention should be paid to the role of fathers in
      smoking prevention.

PMID- 21885674
TI  - Sequential hormonal changes in 21 patients with recurrent Cushing's disease after
      successful pituitary surgery.
AB  - OBJECTIVE: To describe the sequence of hormonal changes during recurrence of
      Cushing's disease (CD) after successful transsphenoidal surgery (TSS). DESIGN:
      Retrospective study in a single center. PATIENTS AND METHODS: We studied 101 of
      the 127 patients treated by TSS for CD between 1996 and 2009, who had
      hypocortisolism or eucortisolism for at least 3 months post-TSS. We arbitrarily
      defined 'overt recurrence', as presence of two classical parameters of excess
      cortisol (increased midnight--either serum or salivary--and 24  h urinary
      cortisol (UC)), leading to further specific therapeutic action, and 'mild
      recurrence', as presence of a single classical parameter, leading to simple
      surveillance. RESULTS: Of the 101 patients, 21 (20.8%) presented with recurrence,
      'mild' or 'overt', during long-term follow-up (median 50.4 months, range 7-99).
      Recurrence occurred less frequently (16.8 vs 50%, P=0.02), and later (mean 44.7
      months, median 43, range 7-94 vs mean 21.5 months, median 17, range 3-61,
      P=0.05), in patients with early post-TSS hypocortisolism compared with those with
      eucortisolism. Increase in midnight cortisol occurred in a mean time of 38.2
      months, while UC elevation was observed at 50.6 months. Vasopressin analogs and
      CRH tests were eventually positive in 85 and 93% of all patients respectively; a
      positive response to one of the two dynamic tests preceded the increase in
      midnight cortisol or UC in 71 and 64% of the patients respectively. CONCLUSION: A
      positive response to vasopressin analogs and/or CRH tests occurs early in
      recurrence, followed by an increase in midnight cortisol, while UC elevation is
      at a later stage.

PMID- 21885675
TI  - Circulating lipocalin 2 is associated with body fat distribution at baseline but
      is not an independent predictor of insulin resistance: the prospective Cyprus
      Metabolism Study.
AB  - OBJECTIVE: Lipocalin 2 (LCN2 or NGAL), a protein derived from neutrophils,
      macrophages, adipocytes, and other cells, has been proposed to be a link between
      obesity and insulin resistance (IR), but animal and cross-sectional human studies
      have revealed conflicting results. We studied the association of serum lipocalin
      2 with anthropometric, metabolic, and cardiovascular risk markers in young
      healthy men cross-sectionally and, for the first time, prospectively after 2
      years of follow-up, with and without adjustment for potential confounders
      including serum creatinine. DESIGN: Two hundred and seventy-two participants were
      randomly selected from the Cyprus Metabolism Study (1056 men, 18 years), of whom
      93 subjects participated in the follow-up study 2 years after baseline
      assessment. Associations were also explored between total and free leptin levels
      (to serve as positive controls) and anthropometric metabolic variables. RESULTS:
      In the cross-sectional study, lipocalin 2 levels were marginally correlated in
      the unadjusted model with central fat distribution but not with body weight or
      total body fat mass. After adjusting for age, smoking, activity, body mass index,
      fat percentage, waist-to-hip ratio, and serum creatinine, no correlation was
      found with any cardiovascular risk factor. There was no correlation with the
      homeostasis model assessment of IR (HOMA-IR) at baseline. In the prospective
      analyses, baseline levels of lipocalin 2 were not predictive of any variables in
      unadjusted or adjusted models. As expected, total and free leptin were associated
      with anthropometric and metabolic variables both cross-sectionally and
      prospectively. CONCLUSIONS: We demonstrate that lipocalin 2 is not an independent
      predictor of metabolic and cardiovascular risk factors in young men cross
      sectionally or prospectively.

PMID- 21885676
TI  - Characterization of a new mouse model of empyema and the mechanisms of pleural
      invasion by Streptococcus pneumoniae.
AB  - Although empyema affects more than 65,000 people each year in the United States
      and in the United Kingdom, there are limited data on the pathogenesis of pleural
      infection. We investigated the pathogenesis of empyema using animal and cell
      culture models of Streptococcus pneumoniae infection. The pathological processes
      during the development of empyema associated with murine pneumonia due to S.
      pneumoniae (strain D39) were investigated. Lungs were examined using histology,
      and pleural fluid and blood bacterial colony-forming units, cytokine levels, and
      cellular infiltrate were determined over time. Bacterial migration across
      mesothelial monolayers was investigated using cell culture techniques, flow
      cytometry, and confocal microscopy. After intranasal inoculation with 10(7) S.
      pneumoniae D39 strain, mice developed pneumonia associated with rapid bacterial
      invasion of the pleural space; raised intrapleural IL-8, VEGF, MCP-1, and TNF
      alpha levels; and caused significant intrapleural neutrophilia followed by the
      development of fibrinous pleural adhesions. Bacterial clearance from the pleural
      space was poor, and in vitro assays demonstrated that S. pneumoniae crossed
      mesothelial layers by translocation through cells rather than by a paracellular
      route. This study describes key events during the development of S. pneumoniae
      empyema using a novel murine model of pneumonia-associated empyema that closely
      mimics human disease. The model allows for future assessment of molecular
      mechanisms involved in the development of empyema and evaluation of potential new
      therapies. The data suggest that transmigration of bacteria through mesothelial
      cells could be important in empyema development. Furthermore, upon entry the
      pleural cavity offers a protected compartment for the bacteria.

PMID- 21885678
TI  - MHC Class II and CD9 in human eosinophils localize to detergent-resistant
      membrane microdomains.
AB  - Eosinophils function in murine allergic airways inflammation as professional
      antigen-presenting cells (APCs). In murine professional APC cell types, optimal
      functioning of MHC Class II depends on its lateral association in plasma
      membranes and colocalization with the tetraspanin CD9 into detergent-resistant
      membrane microdomains (DRMs). With human eosinophils, we evaluated the
      localization of MHC Class II (HLA-DR) to DRMs and the functional significance of
      such localization. In granulocyte-macrophage colony-stimulating factor-stimulated
      human eosinophils, antibody cross-linked HLA-DR colocalized by immunofluorescence
      microscopy focally on plasma membranes with CD9 and the DRM marker ganglioside
      GM1. In addition, HLA-DR coimmunoprecipitates with CD9 after chemical cross
      linking of CD9. HLA-DR and CD9 were localized by Western blotting in eosinophil
      DRM subcellular fractions. DRM disruption with the cholesterol-depleting agent
      methyl-beta-cyclodextrin decreased eosinophil surface expression of HLA-DR and
      CD9. We show that CD9 is abundant on the surface of eosinophils, presenting the
      first electron microscopy data of the ultrastructural immunolocalization of CD9
      in human eosinophils. Disruption of HLA-DR-containing DRMs decreased the ability
      of superantigen-loaded human eosinophils to stimulate CD4(+) T-cell activation
      (CD69 expression), proliferation, and cytokine production. Our results, which
      demonstrate that eosinophil MHC Class II localizes to DRMs in association with
      CD9 in a functionally significant manner, represent a novel insight into the
      organization of the antigen presentation complex of human eosinophils.

PMID- 21885679
TI  - A common evolutionary origin for tailed-bacteriophage functional modules and
      bacterial machineries.
AB  - Bacteriophages belonging to the order Caudovirales possess a tail acting as a
      molecular nanomachine used during infection to recognize the host cell wall,
      attach to it, pierce it, and ensure the high-efficiency delivery of the genomic
      DNA to the host cytoplasm. In this review, we provide a comprehensive analysis of
      the various proteins constituting tailed bacteriophages from a structural
      viewpoint. To this end, we had in mind to pinpoint the resemblances within and
      between functional modules such as capsid/tail connectors, the tails themselves,
      or the tail distal host recognition devices, termed baseplates. This comparison
      has been extended to bacterial machineries embedded in the cell wall, for which
      shared molecular homology with phages has been recently revealed. This is the
      case for the type VI secretion system (T6SS), an inverted phage tail at the
      bacterial surface, or bacteriocins. Gathering all these data, we propose that a
      unique ancestral protein fold may have given rise to a large number of
      bacteriophage modules as well as to some related bacterial machinery components.

PMID- 21885680
TI  - Molecular mechanism of scanning and start codon selection in eukaryotes.
AB  - The correct translation of mRNA depends critically on the ability to initiate at
      the right AUG codon. For most mRNAs in eukaryotic cells, this is accomplished by
      the scanning mechanism, wherein the small (40S) ribosomal subunit attaches to the
      5' end of the mRNA and then inspects the leader base by base for an AUG in a
      suitable context, using complementarity with the anticodon of methionyl initiator
      tRNA (Met-tRNAiMet) as the key means of identifying AUG. Over the past decade, a
      combination of yeast genetics, biochemical analysis in reconstituted systems, and
      structural biology has enabled great progress in deciphering the mechanism of
      ribosomal scanning. A robust molecular model now exists, describing the roles of
      initiation factors, notably eukaryotic initiation factor 1 (eIF1) and eIF1A, in
      stabilizing an "open" conformation of the 40S subunit with Met-tRNAiMet bound in
      a low-affinity state conducive to scanning and in triggering rearrangement into a
      "closed" conformation incompatible with scanning, which features Met-tRNAiMet
      more tightly bound to the "P" site and base paired with AUG. It has also emerged
      that multiple DEAD-box RNA helicases participate in producing a single-stranded
      "landing pad" for the 40S subunit and in removing the secondary structure to
      enable the mRNA to traverse the 40S mRNA-binding channel in the single-stranded
      form for base-by-base inspection in the P site.

PMID- 21885684
TI  - Variability in the muscle composition of rat esophagus and neural pathway of
      lower esophageal sphincter relaxation.
AB  - Several studies from our laboratory show that axial stretch of the lower
      esophageal sphincter (LES) in an oral direction causes neurally mediated LES
      relaxation. Under physiological conditions, axial stretch of the LES is caused by
      longitudinal muscle contraction (LMC) of the esophagus. Because longitudinal
      muscle is composed of skeletal muscle in mice, vagal-induced LMC and LES
      relaxation are both blocked by pancuronium. We conducted studies in rats (thought
      to have skeletal muscle esophagus) to determine if vagus nerve-mediated LES
      relaxation is also blocked by pancuronium. LMC-mediated axial stretch on the LES
      was monitored using piezoelectric crystals. LES and esophageal pressures were
      monitored with a 2.5-Fr solid-state pressure transducer catheter. Following
      bilateral cervical vagotomy, the vagus nerve was stimulated electrically. LES,
      along with the esophagus, was harvested after in vivo experiments and
      immunostained for smooth muscle (smooth muscle alpha-actin) and skeletal muscle
      (fast myosin heavy chain). Vagus nerve-stimulated LES relaxation and esophageal
      LMC were reduced in a dose-dependent fashion and completely abolished by
      pancuronium (96 MUg/kg) in six rats (group 1). On the other hand, in seven rats,
      LES relaxation and LMC were only blocked completely by a combination of
      pancuronium (group 2) and hexamethonium. Immunostaining revealed that the
      longitudinal muscle layer was composed of predominantly skeletal muscle in the
      group 1 rats. On the other hand, the longitudinal muscle layer of group 2 rats
      contained a significant amount of smooth muscle (P < 0.05). Our study shows tight
      coupling between axial stretch on the LES and relaxation of the LES, which
      suggests a cause and effect relationship between the two. We propose that the
      vagus nerve fibers that cause LMC induce LES relaxation through the stretch
      sensitive activation of inhibitory motor neurons.

PMID- 21885685
TI  - Evidence for altered circular smooth muscle cell function in lower esophageal
      sphincter of W/Wv mutant mice.
AB  - Nitrergic neurotransmission to gut smooth muscle is impaired in W/W(v) mutant
      mice, which lack intramuscular interstitial cells of Cajal (ICC-IM). In addition,
      these mice have been reported to have smaller amplitude unitary potentials (UPs)
      and a more negative resting membrane potential (RMP) than control mice. These
      abnormalities have been attributed to absence of ICC-IM, but it remains possible
      that they are due to alterations at the level of the smooth muscle itself.
      Amphotericin-B-perforated patch-clamp recordings and Ca(2+) imaging (fura 2) were
      compared between freshly isolated single circular smooth muscle cells (CSM) from
      W/W(v) mutant and control mice lower esophageal sphincter (LES). There was no
      significant difference in seal resistance, capacitance, or input resistance in
      response to applied electrotonic current pulses between CSM cells from W/W(v)
      mutants and controls. Compared with control mice, RMP was more negative and UPs
      significantly smaller in CSM cells from mutant mice LES. Administration of
      caffeine induced an inward current in cells from both mutant and control mice,
      but the current density was significantly larger in cells from W/W(v) mutants.
      Membrane potential hyperpolarization induced by sodium nitroprusside was larger
      in cells from control mice vs. W/W(v) mutants. In addition, intracellular Ca(2+)
      transients induced by caffeine were significantly increased in cells from
      mutants. These findings indicate that LES CSM is abnormal in W/W(v) mutant mice.
      Thus some physiological functions attributed to ICC-IM based on experiments in
      smooth muscle of ICC deficient mice may need to be reconsidered.

PMID- 21885682
TI  - From water and ions to crowded biomacromolecules: in vivo structuring of a
      prokaryotic cell.
AB  - The interactions and processes which structure prokaryotic cytoplasm (water,
      ions, metabolites, and biomacromolecules) and ensure the fidelity of the cell
      cycle are reviewed from a physicochemical perspective. Recent spectroscopic and
      biological evidence shows that water has no active structuring role in the
      cytoplasm, an unnecessary notion still entertained in the literature; water acts
      only as a normal solvent and biochemical reactant. Subcellular structuring arises
      from localizations and interactions of biomacromolecules and from the growth and
      modifications of their surfaces by catalytic reactions. Biomacromolecular
      crowding is a fundamental physicochemical characteristic of cells in vivo. Though
      some biochemical and physiological effects of crowding (excluded volume effect)
      have been documented, crowding assays with polyglycols, dextrans, etc., do not
      properly mimic the compositional variety of biomacromolecules in vivo. In vitro
      crowding assays are now being designed with proteins, which better reflect
      biomacromolecular environments in vivo, allowing for hydrophobic bonding and
      screened electrostatic interactions. I elaborate further the concept of complex
      vectorial biochemistry, where crowded biomacromolecules structure the cytosol
      into electrolyte pathways and nanopools that electrochemically "wire" the cell.
      Noncovalent attractions between biomacromolecules transiently supercrowd
      biomacromolecules into vectorial, semiconducting multiplexes with a high (35 to
      95%)-volume fraction of biomacromolecules; consequently, reservoirs of less
      crowded cytosol appear in order to maintain the experimental average crowding of
      ~25% volume fraction. This nonuniform crowding model allows for fast diffusion of
      biomacromolecules in the uncrowded cytosolic reservoirs, while the supercrowded
      vectorial multiplexes conserve the remarkable repeatability of the cell cycle by
      preventing confusing cross talk of concurrent biochemical reactions.

PMID- 21885686
TI  - Estrogen deficiency worsens steatohepatitis in mice fed high-fat and high
      cholesterol diet.
AB  - Recent studies indicate an accelerated progression of nonalcoholic
      steatohepatitis (NASH) in postmenopausal women. Hypercholesterolemia, an
      important risk factor for NASH progression, is often observed after menopause.
      This study examined the effects of estrogen on NASH in ovariectomized (OVX) mice
      fed a high-fat and high-cholesterol (HFHC) diet. To investigate the effects of
      estrogen deficiency, OVX mice and sham-operated (SO) mice were fed normal chow or
      HFHC diet for 6 wk. Next, to investigate the effects of exogenous estrogen
      replenishment, OVX mice fed with HFHC diet were treated with implanted hormone
      release pellets (containing 17beta-estradiol or placebo vehicle) for 6 wk. OVX
      mice on the HFHC diet showed enhanced liver injury with increased liver
      macrophage infiltration and elevated serum cholesterol levels compared with SO
      HFHC mice. Hepatocyte monocyte chemoattractant protein-1 (MCP1) protein
      expression in OVX-HFHC mice was also enhanced compared with SO-HFHC mice. In
      addition, hepatic inflammatory gene expressions, including monocytes chemokine (C
      C motif) receptor 2 (CCR2), were significantly elevated in OVX-HFHC mice.
      Estrogen treatment improved serum cholesterol levels, liver injury, macrophage
      infiltration, and inflammatory gene expressions in OVX-HFHC mice. Moreover, the
      elevated expression of liver CCR2 and MCP1 were decreased by estrogen treatment
      in OVX-HFHC mice, whereas low-density lipoprotein dose dependently enhanced CCR2
      expression in THP1 monocytes. Our study demonstrated that estrogen deficiency
      accelerated NASH progression in OVX mice fed HFHC diet and that this effect was
      improved by estrogen therapy. Hypercholesterolemia in postmenopausal women would
      be a potential risk factor for NASH progression.

PMID- 21885687
TI  - Cocktail approach for in vivo phenotyping of 5 major CYP450 isoenzymes:
      development of an effective sampling, extraction, and analytical procedure and
      pilot study with comparative genotyping.
AB  - In this study, the authors developed a phenotyping method for CYP1A2, 2C9, 2C19,
      2D6, and 3A4 using a cocktail of 100 mg caffeine, 125 mg tolbutamide, 20 mg
      omeprazole, 30 mg dextromethorphan, and 2 mg midazolam. A simple sampling scheme
      was established collecting 3 blood samples at 0, 4, and 24 hours followed by
      solid-phase extraction and liquid chromatography/tandem mass spectrometry
      analysis. After addition of 8 deuterated internal standards and extraction, the
      analytes were separated using gradient elution with ammonium acetate and
      methanol. Data acquisition was performed on a triple quadrupole linear ion trap
      mass spectrometer in multiple-reaction monitoring mode with positive electrospray
      ionization. The assay was validated according to international guidelines: limits
      of quantification (LOQs) were between 0.25 and 1.0 ng/mL for all analytes, except
      for paraxanthine and caffeine (20 ng/mL). Extraction efficiencies ranged between
      77% and 103% and matrix effects between 23% and 95%; precision and accuracy data
      fulfilled accepted criteria. Calibration curves from LOQ to 1000 ng/mL were
      established for undiluted and 1:10 diluted plasma (r > 0.998). The method was
      tested in a pilot study with 14 volunteers. Additional genotyping of the probands
      generally demonstrated good accordance with the measured phenotyping indices but
      also disclosed certain contradictory results.

PMID- 21885681
TI  - Interplay between innate immunity and negative-strand RNA viruses: towards a
      rational model.
AB  - The discovery of a new class of cytosolic receptors recognizing viral RNA, called
      the RIG-like receptors (RLRs), has revolutionized our understanding of the
      interplay between viruses and host cells. A tremendous amount of work has been
      accumulating to decipher the RNA moieties required for an RLR agonist, the signal
      transduction pathway leading to activation of the innate immunity orchestrated by
      type I interferon (IFN), the cellular and viral regulators of this pathway, and
      the viral inhibitors of the innate immune response. Previous reviews have focused
      on the RLR signaling pathway and on the negative regulation of the interferon
      response by viral proteins. The focus of this review is to put this knowledge in
      the context of the virus replication cycle within a cell. Likewise, there has
      been an expansion of knowledge about the role of innate immunity in the
      pathophysiology of viral infection. As a consequence, some discrepancies have
      arisen between the current models of cell-intrinsic innate immunity and current
      knowledge of virus biology. This holds particularly true for the nonsegmented
      negative-strand viruses (Mononegavirales), which paradoxically have been largely
      used to build presently available models. The aim of this review is to bridge the
      gap between the virology and innate immunity to favor the rational building of a
      relevant model(s) describing the interplay between Mononegavirales and the innate
      immune system.

PMID- 21885683
TI  - The universally conserved prokaryotic GTPases.
AB  - Members of the large superclass of P-loop GTPases share a core domain with a
      conserved three-dimensional structure. In eukaryotes, these proteins are
      implicated in various crucial cellular processes, including translation, membrane
      trafficking, cell cycle progression, and membrane signaling. As targets of
      mutation and toxins, GTPases are involved in the pathogenesis of cancer and
      infectious diseases. In prokaryotes also, it is hard to overestimate the
      importance of GTPases in cell physiology. Numerous papers have shed new light on
      the role of bacterial GTPases in cell cycle regulation, ribosome assembly, the
      stress response, and other cellular processes. Moreover, bacterial GTPases have
      been identified as high-potential drug targets. A key paper published over 2
      decades ago stated that, "It may never again be possible to capture [GTPases] in
      a family portrait" (H. R. Bourne, D. A. Sanders, and F. McCormick, Nature 348:125
      132, 1990) and indeed, the last 20 years have seen a tremendous increase in
      publications on the subject. Sequence analysis identified 13 bacterial GTPases
      that are conserved in at least 75% of all bacterial species. We here provide an
      overview of these 13 protein subfamilies, covering their cellular functions as
      well as cellular localization and expression levels, three-dimensional
      structures, biochemical properties, and gene organization. Conserved roles in
      eukaryotic homologs will be discussed as well. A comprehensive overview
      summarizing current knowledge on prokaryotic GTPases will aid in further
      elucidating the function of these important proteins.

PMID- 21885688
TI  - When to stop treating the bones.

PMID- 21885689
TI  - Accountable care organizations, the patient-centered medical home, and health
      care reform: what does it all mean?
AB  - Medical care in the United States is plagued by extremely high costs, poor
      quality, and fragmented delivery. In response, new concepts of integrated health
      care delivery have developed, including patient-centered medical homes and
      accountable care organizations (ACOs). This article reviews these concepts and
      includes a detailed discussion of the Centers for Medicare and Medicaid Services'
      ACO and Shared Savings Proposed Rule.

PMID- 21885691
TI  - Oral plaques and dysphagia in a young man.

PMID- 21885690
TI  - Allergy blood testing: A practical guide for clinicians.
AB  - Blood tests are available that measure levels of immunoglobulin E (IgE) against
      specific allergens such as foods, inhalants, medications, latex, and venoms.
      These tests can confirm the diagnosis of an allergic disorder, supplementing a
      clinical history consistent with an immediate allergic reaction. They are
      particularly useful when skin testing cannot or should not be performed.

PMID- 21885693
TI  - Unmasking gastric cancer.

PMID- 21885692
TI  - Hepatic encephalopathy: suspect it early in patients with cirrhosis.
AB  - As viral hepatitis and nonalcoholic fatty liver disease continue to increase in
      prevalence, we will see more cases of hepatic encephalopathy. Primary care
      physicians are often the first to suspect it, as they are familiar with the
      patient's usual mental and physical status. This serious complication typically
      occurs in patients with severe comorbidities and requires multidisciplinary
      evaluation and care.

PMID- 21885694
TI  - Venous thromboembolism: what to do after anticoagulation is started.
AB  - After anticoagulation has been started in patients with venous thromboembolism
      (VTE), three issues need to be addressed: the length of therapy, measures to help
      prevent postthrombotic syndrome, and a basic workup for malignancy in patients
      with idiopathic VTE.

PMID- 21885695
TI  - What is the optimal duration of bisphosphonate therapy?
AB  - It is reasonable to stop bisphosphonates after 5 years of use and then to follow
      patients with markers of bone turnover. As long as the levels of these markers
      remain reduced, adding an antiresorptive drug does not make physiologic sense.

PMID- 21885696
TI  - Posttraumatic stress disorders in civilian orthopaedics.

PMID- 21885697
TI  - Classic bladder exstrophy: orthopaedic surgical considerations.
AB  - Classic bladder exstrophy is an embryologic malformation that results in complex
      deficiency of the anterior midline, with urogenital and skeletal manifestations.
      Urogenital reconstruction is a challenging procedure that can be facilitated by
      closure of the bony pelvic ring by an orthopaedic team. Surgical options include
      a multiyear staged approach and the single-stage complete repair for exstrophy.
      The goals of urologic surgery include closure of the bladder and abdominal wall
      with eventual bladder continence, preservation of renal function, and cosmetic
      and functional reconstruction of the genitalia. Pelvic osteotomy is done at the
      time of bladder closure in the patient in whom the anterior pelvis cannot be
      approximated without tension. Traction or spica casting is used postoperatively.
      Good outcomes are probable with appropriate management at specialized treatment
      centers.

PMID- 21885698
TI  - All-polyethylene tibial components in modern total knee arthroplasty.
AB  - Most total knee arthroplasty prostheses have modular tibial components with metal
      backed tibial baseplates. Biomechanical studies have demonstrated mechanical
      advantages to a metal-backed tibial component in terms of tibial load transfer.
      In addition, tibial component modularity provides intraoperative flexibility and
      may provide an advantage in the setting of subsequent revision knee surgery.
      However, clinical evidence does not support the preferential use of metal-backed
      tibial components. Modularity introduces the potential for backside wear and
      associated osteolysis. Also, several recent studies have shown no significant
      differences in clinical and radiographic outcomes between metal-backed and all
      polyethylene tibial components. In addition, all-polyethylene tibial components
      are less expensive than metal-backed components; increased usage of all
      polyethylene components could help decrease the cost of health care.

PMID- 21885699
TI  - Adhesive capsulitis of the shoulder.
AB  - Adhesive capsulitis is characterized by painful, gradual loss of active and
      passive shoulder motion resulting from fibrosis and contracture of the joint
      capsule. Other shoulder pathology can produce a similar clinical picture,
      however, and must be considered. Management is based on the underlying cause of
      pain and stiffness, and determination of the etiology is essential. Subtle clues
      in the history and physical examination can help differentiate adhesive
      capsulitis from other conditions that cause a stiff, painful shoulder. The
      natural history of adhesive capsulitis is a matter of controversy. Management of
      true capsular restriction of motion (ie, true adhesive capsulitis) begins with
      gentle, progressive stretching exercises. Most patients improve with nonsurgical
      treatment. Indications for surgery should be individualized. Failure to obtain
      symptomatic improvement and continued functional disability following >=6 months
      of physical therapy is a general guideline for surgical intervention. Diligent
      postoperative therapy to maintain motion is required to minimize recurrence of
      adhesive capsulitis.

PMID- 21885701
TI  - Perilunate dislocation and perilunate fracture-dislocation.
AB  - Perilunate dislocations and perilunate fracture-dislocations usually result from
      high-energy traumatic injuries to the wrist and are associated with a
      characteristic spectrum of bony and ligamentous damage. Radiographic evaluation
      of the wrist reveals loss of normal radiocarpal and intercarpal colinearity and
      bony insult, which may be overlooked at the initial presentation. Prompt
      recognition is important to optimize outcomes. Closed reduction is performed
      acutely, followed by open reduction and ligamentous and bony repair with internal
      fixation. Complications include posttraumatic arthrosis, median nerve
      dysfunction, complex regional pain syndrome, tendon problems, and carpal
      instability. Despite appropriate treatment, loss of wrist motion and grip
      strength, as well as persistent pain, is common. Medium- and long-term studies
      demonstrate radiographic evidence of midcarpal and radiocarpal arthrosis,
      although this does not correlate with functional outcomes.

PMID- 21885700
TI  - Intervertebral disk degeneration and emerging biologic treatments.
AB  - Although understanding of the biologic basis of intervertebral disk (IVD)
      degeneration is rapidly advancing, the unique IVD environment presents challenges
      to the development and delivery of biologic treatments. Acceleration of cellular
      senescence and apoptosis in degenerative IVDs and the depletion of matrix
      proteins have prompted the development of treatments based on replacing IVD cells
      using various cell sources. However, this strategy has not been tested in animal
      models. IVD degeneration and associated pain have led to interest in pathologic
      innervation of the IVD and ultimately to the development of percutaneous devices
      to ablate afferent nerve endings in the posterior annulus. Degeneration leads to
      changes in the expression of matrix protein, cytokines, and proteinases.
      Injection of growth factors and mitogens may help overcome these degenerative
      changes in IVD phenotype, and these potential treatments are being explored in
      animal studies. Gene therapy is an elegant method to address changes in protein
      expression, but efforts to apply this technology to IVD degeneration are still at
      early stages.

PMID- 21885702
TI  - Management of aseptic tibial nonunion.
AB  - Tibial nonunion remains a significant clinical challenge despite advances in
      surgical management. New techniques to help manage tibial nonunion include
      extracorporeal shock wave therapy and percutaneous application of bone marrow
      aspirate. Management strategies vary based on the type of nonunion: aseptic or
      infected, and atrophic or hypertrophic. Extracorporeal shock wave therapy has
      been shown to be as effective as surgical management in patients with stable
      hypertrophic nonunion. New fixation options include locked plates and
      intramedullary compression nails. Novel methods of external fixation have been
      developed for bone graft harvest from the intramedullary canal. Several biologic
      adjuncts also are available, including bone marrow aspirates, stem cells, and
      bone morphogenetic protein.

PMID- 21885703
TI  - The effect of drill bit, pin, and wire tip design on drilling.
AB  - Successful penetration of bone is dependent on several factors, including bone
      quality, drill bit and pin design, and drilling technique. Wires are also used in
      bone drilling, and the tip configuration can affect the efficiency of bone
      penetration. Incorrect use of drill bits, pins, and wires may result in
      complications such as thermal necrosis and hardware breakage.

PMID- 21885704
TI  - An approach to assessing data quality in an area probability survey using CBPR.
AB  - Community-based participatory research (CBPR) approaches attempt to engage
      community members in all aspects of research conducted in the community.
      Proponents of CBPR suggest that among the many advantages to using CBPR is higher
      acceptance of and cooperation in research endeavors than is usually achieved
      through more traditional research approaches. Using secondary analysis of sample
      disposition data from two area probability surveys of the same community areas,
      one involving community interviewers in a fully collegial CBPR study and the
      other using professional interviewers, this study finds that data collected using
      CBPR techniques may lead to higher cooperation and lower refusal rates than data
      collected by professional interviewers. However, when compared to external
      population indicators such as census data, the sample produced by CBPR
      interviewers overrepresents certain population groups whereas the survey data
      produced by professional interviewers may underrepresent key population groups.

PMID- 21885705
TI  - The relationship of perceived neighborhood social climate to walking in Hispanic
      older adults: a longitudinal, cross-lagged panel analysis.
AB  - OBJECTIVE: This study examines possible bidirectional relationships between
      neighborhood climate (i.e., perceived neighborhood social environment) and
      walking behavior across a 12-month period in older Hispanics. METHOD: A
      population-based sample of 217 community-dwelling older Hispanics in Miami,
      Florida, completed measures of perceived neighborhood climate and neighborhood
      walking, at two assessment time points (12 months apart). RESULTS: Structural
      equation modeling analyses revealed that neighborhood climate predicted
      subsequent walking 12 months later, such that more positive perceptions of
      neighborhood climate predicted more walking. Follow-up analyses revealed that
      older adults who resided in the top half of neighborhoods based on perceived
      neighborhood climate scores at initial assessment were 2.57 times as likely to
      have walked at least one block in the last week at follow-up, relative to older
      adults residing in neighborhoods whose climate was in the lower half. DISCUSSION:
      Perceptions of a more positive neighborhood social environment may promote
      walking in urban, older Hispanics.

PMID- 21885706
TI  - PartyIntents: a portal survey to assess gay and bisexual men's risk behaviors at
      weekend parties.
AB  - PartyIntents examines whether portal survey methods could be used to anonymously
      survey gay and bisexual men about HIV-risk behaviors before and after a weekend
      party-oriented vacation. The study recruited 97% of eligible men and of these 489
      participants 47% completed the follow-up assessment. Approximately one half of
      the men intended to use illegal drugs over the weekend, and almost 20% thought
      that they might have anal intercourse and not use a condom. The methodology can
      be applied and provides useful information about HIV risk at these events, though
      refinements may be needed to increase the follow-up rates.

PMID- 21885707
TI  - The citizen psychoanalyst: psychoanalysis, social commentary, and social
      advocacy.

PMID- 21885708
TI  - Introduction to Weinberger and Smith.

PMID- 21885710
TI  - Psychoanalytically informed psychotherapy of psychosis: the influences of
      american psychoanalysis. Panel report.

PMID- 21885711
TI  - The association between the duration of preoperative pain and pain improvement in
      vertebral augmentation: a meta-analysis.
AB  - BACKGROUND AND PURPOSE: Most physicians consider length of preoperative pain as
      an important factor to include patients for SA. Our aim was to synthesize the
      available evidence regarding the influence of preprocedural pain duration on the
      outcome of vertebral augmentation procedures. MATERIALS AND METHODS: The MEDLINE
      data base was reviewed up to March 2010. Meta-regression and mixed-effect
      subgroup analyses were performed to evaluate the association between the outcome
      of interest, which was pain improvement assessed by a VAS (0-10) and the duration
      of preoperative pain (independent variable). RESULTS: We included 17 articles.
      The mean VAS improvements for subgroups of <=6 weeks (n = 12), 6-24 weeks (n =
      5), and >24 weeks (n = 3) were 5.18, 4.90, and 5.04, respectively (P = .86). The
      regression coefficient was -0.024, suggesting trivial association of the duration
      of preoperative pain and pain improvement. CONCLUSIONS: Pain relief following
      spine augmentation was similar among groups of patients with varying lengths of
      preoperative pain duration.

PMID- 21885713
TI  - Impact of brain tumor location on morbidity and mortality: a retrospective
      functional MR imaging study.
AB  - BACKGROUND AND PURPOSE: fMRI is increasingly used in neurosurgery to
      preoperatively identify areas of eloquent cortex. Our study evaluated the
      efficacy of clinical fMRI by analyzing the relationship between the distance from
      the tumor border to the area of functional activation (LAD) and patient pre- and
      postoperative morbidity and mortality. MATERIALS AND METHODS: The study included
      patients with diagnosis of primary or metastatic brain tumor who underwent
      preoperative fMRI-based motor mapping (n=74) and/or language mapping (n=77). The
      impact of LAD and other variables collected from patient records was analyzed
      with respect to functional deficits in terms of morbidity (paresis and aphasia)
      and mortality. RESULTS: Significant relationships were found between motor and
      language LAD and the existence of either pre- or postoperative motor (P < .001)
      and language deficits (P=.009). Increasing age was associated with motor and
      language deficits (P=.02 and P=.04 respectively). Right-handedness was related to
      language deficits (P=.05). Survival analysis revealed that pre- and postoperative
      deficits, grade, tumor location, and LAD predicted mortality. Motor deficits
      increased linearly as the distance from the tumor to the primary sensorimotor
      cortex decreased. Language deficits increased exponentially as the distance from
      the tumor to the language areas decreased below 1 cm. Postoperative mortality
      analysis showed an interaction effect between motor or language LAD and mortality
      predictors (grade and tumor location, respectively). CONCLUSIONS: These findings
      indicate that tumors may affect language and motor function differently depending
      on tumor LAD. Overall, the data support the use of fMRI as a tool to evaluate
      patient prognosis and are directly applicable to neurosurgical planning.

PMID- 21885712
TI  - How do coil configuration and packing density influence intra-aneurysmal
      hemodynamics?
AB  - BACKGROUND AND PURPOSE: Endovascular coiling is a well-established therapy for
      treating intracranial aneurysms. Nonetheless, postoperative hemodynamic changes
      induced by this therapy remain not fully understood. The purpose of this work is
      to assess the influence of coil configuration and packing density on intra
      aneurysmal hemodynamics. MATERIALS AND METHODS: Three 3D rotational angiography
      images of 3 intracranial aneurysms before and after endovascular coiling were
      used. For each aneurysm, a 3D representation of the vasculature was obtained
      after the segmentation of the images. Afterward, a virtual coiling technique was
      used to treat the aneurysm geometries with coil models. The aneurysms were coiled
      with 5 packing densities, and each was generated by using 3 coil configurations.
      Computational fluid dynamics analyses were carried out in both untreated and
      treated aneurysm geometries. Statistical tests were performed to evaluate the
      relative effect of coil configuration on local hemodynamics. RESULTS: The intra
      aneurysmal blood flow velocity and wall shear stress were diminished as packing
      density increased. Aneurysmal flow velocity was reduced >50% due to the first
      inserted coils (packing density <12%) but with a high dependency on coil
      configuration. Nonsignificant differences (P > .01) were found in the
      hemodynamics due to coil configuration for high packing densities (near 30%). A
      damping effect was observed on the intra-aneurysmal blood flow waveform after
      coiling. CONCLUSIONS: Intra-aneurysmal hemodynamics are altered by coils. Coil
      configuration might reduce its influence on intra-aneurysmal hemodynamics as the
      packing density increases until an insignificant influence could be achieved for
      high packing densities.

PMID- 21885714
TI  - Early rate of contrast extravasation in patients with intracerebral hemorrhage.
AB  - BACKGROUND AND PURPOSE: For patients with ICH, knowing the rate of CT contrast
      extravasation may provide insight into the pathophysiology of hematoma expansion.
      This study assessed whether the PCT-derived PS can measure different rates of CT
      contrast extravasation for admission CTA spot signs, PCCT, PCL, and regions
      without extravasation in patients with ICH. MATERIALS AND METHODS: CT was
      performed at admission and at 24 hours for 16 patients with ICH with/without
      contrast extravasation seen on CTA and PCCT. PCT-PS was measured at admission.
      The Wilcoxon rank sum test with a Bonferroni correction was used to compare PS
      values from the following regions of interest: 1) spot sign lesions only (9
      foci), 2) PCL lesions only (9 foci), 3) hematoma excluding extravasation, 4)
      regions contralateral to extravasation, 5) hematoma in patients without
      extravasation, and 6) an area contralateral to that in 5. Additionally, hematoma
      expansion was determined at 24 hours defined by NCCT. RESULTS: PS was 6.5 +/-
      1.60 mL . min(-1) * (100 g)(-1), 0.95 +/- 0.39 mL . min(-1) * (100 g)(-1), 0.12
      +/- 0.39 mL . min(-1) * (100 g)(-1), 0.26 +/- 0.09 mL . min(-1) * (100 g)(-1),
      0.38 +/- 0.26 mL . min(-1) * (100 g)(-1), and 0.09 +/- 0.32 mL . min(-1) * (100
      g)(-1) for the following: 1) spot sign lesions only (9 foci), 2) PCL lesions only
      (9 foci), 3) hematoma excluding extravasation, 4) regions contralateral to
      extravasation, 5) hematoma in patients without extravasation, and 6) an area
      contralateral to that in 5. PS values from spot sign lesions and PCL lesions were
      significantly different from each other and all other regions, respectively (P <
      .05). Hematoma volume increased from 34.1 +/- 41.0 mL to 40.2 +/- 46.1 mL in
      extravasation-positive patients and decreased from 19.8 +/- 31.8 mL to 17.4 +/-
      27.3 mL in extravasation-negative patients. CONCLUSIONS: The PCT-PS parameter
      measures a higher rate of contrast extravasation for CTA spot sign lesions
      compared with PCL lesions and hematoma. Early extravasation was associated with
      hematoma expansion.

PMID- 21885715
TI  - Neurovascular in-stent stenoses: treatment with conventional and drug-eluting
      balloons.
AB  - BACKGROUND AND PURPOSE: ISRs remain a major issue in the endovascular management
      of ICAD, requiring retreatment by reangioplasty. The aim of the present study was
      to evaluate the technical feasibility, safety, and efficiency of the novel DEBs
      for neurovascular ISRs. MATERIALS AND METHODS: Fifty-one patients (median age, 67
      years; age range, 34-82 years; male/female ratio, 37:14) underwent 63 balloon
      dilation procedures for ISRs in intracranial stented arterial segments between
      November 2007 and August 2010 in a single center. Of the 63 procedures, 20 (32%)
      were performed by using a conventional balloon and 43 (68%), by using a
      paclitaxel-eluting balloon (SeQuent Please). Angiographic and clinical follow-up
      was performed at 6 and 12 weeks, 6 and 12 months, and yearly thereafter.
      Technical success rate, periprocedural complications, occurrence of recurrent
      ischemic symptoms, and the development of a recurrent ISR after reangioplasty
      were analyzed. RESULTS: Technical success, defined as <50% residual stenosis was
      achieved in all cases (100%), with failure of the DEB treatment in 6% of the
      attempts; those lesions were finally successfully treated with a conventional
      balloon. The combined permanent neurologic morbidity and mortality rate (stroke,
      ICH, and SAH) at 30 days was 1.6%. Substantial difference was found in the rate
      of recurrent stenosis when comparing conventional balloons and DEBs, with
      recurrent stenosis rates of 50% and 9%, respectively. CONCLUSIONS: The initial
      results of reangioplasty of intracranial ISRs with DEBs are encouraging; further
      technical developments are, nevertheless, mandatory.

PMID- 21885716
TI  - Functional connectivity targeting for deep brain stimulation in essential tremor.
AB  - BACKGROUND AND PURPOSE: Deep brain stimulation of the thalamus has become a
      valuable treatment for medication-refractory essential tremor, but current
      targeting provides only a limited ability to account for individual anatomic
      variability. We examined whether functional connectivity measurements among the
      motor cortex, superior cerebellum, and thalamus would allow discrimination of
      precise targets useful for image guidance of neurostimulator placement. MATERIALS
      AND METHODS: Resting BOLD images (8 minutes) were obtained in 58 healthy
      adolescent and adult volunteers. Regions of interest were identified from an
      anatomic atlas and a finger movement task in each subject in the primary motor
      cortex and motor activation region of the bilateral superior cerebellum.
      Correlation was measured in the time series of each thalamic voxel with the 4
      seeds. An analogous procedure was performed on a single subject imaged for 10
      hours to constrain the time needed for single-subject optimization of thalamic
      targets. RESULTS: Mean connectivity images from 58 subjects showed precisely
      localized targets within the expected location of the ventral intermediate
      nucleus of the thalamus, within a single voxel of currently used deep brain
      stimulation anatomic targets. These targets could be mapped with single-voxel
      accuracy in a single subject with 3 hours of imaging time, though targets were
      reproduced in different locations for the individual than for the group averages.
      CONCLUSIONS: Interindividual variability likely exists in optimal placement for
      thalamic deep brain stimulation targeting of the cerebellar thalamus for
      essential tremor. Individualized thalamic targets can be precisely estimated for
      image guidance with sufficient imaging time.

PMID- 21885718
TI  - Analysis of correlation between the number of lenticulostriate arteries and
      hypertension based on high-resolution MR angiography findings.
AB  - BACKGROUND AND PURPOSE: Hypertension, one of the most important risk factors for
      strokes, is associated with altered arterial anatomy and function. In this study,
      we compared the visualization of the LSAs by 3T 3D-TOF-MRA and DSA and
      quantitatively examined the LSAs in patients with hypertension by using 3D-TOF
      MRA. MATERIALS AND METHODS: We first examined 126 patients with 3D-TOF-MRA and
      DSA and determined the number of LSAs. In addition, we examined 60 patients with
      hypertension and 60 nonhypertensive volunteers with 3D-TOF-MRA and determined the
      quantitative differences between the LSAs of these 2 groups. RESULTS: The mean
      number of LSA stems visualized by DSA and 3D-TOF-MRA on 1 side was 4.1 +/- 0.74
      and 3.9 +/- 0.94, respectively (P = .0617). The average number of LSA stems on
      both sides was 4.7 +/- 0.8 in patients with hypertension and 6.3 +/- 1.9 in
      nonhypertensive volunteers (P < .0001). The mean number of LSAs in the young
      hypertensive group (<50 years of age) and its age-matched nonhypertensive group
      was 4.8 +/- 1.1 and 7.6 +/- 1.2, respectively (P < .0001) and that in the old
      hypertensive group (>=50 years of age) and its age-matched nonhypertensive group
      was 4.6 +/- 0.9 and 5.0 +/- 1.0, respectively (P = .1088). CONCLUSIONS: LSA
      detection showed good correlation between 3T 3D-TOF-MRA and DSA. As determined by
      3D-TOF-MRA, there was a significant decrease in the number of LSA stems in
      patients with hypertension compared with that in nonhypertensive volunteers;
      moreover, the difference in young subjects was more than that in the elderly.

PMID- 21885717
TI  - Brain iron quantification in mild traumatic brain injury: a magnetic field
      correlation study.
AB  - BACKGROUND AND PURPOSE: Experimental studies have suggested a role for iron
      accumulation in the pathology of TBI. Magnetic field correlation MR imaging is
      sensitive to the presence of non-heme iron. The aims of this study are to 1)
      assess the presence, if any, and the extent of iron deposition in the deep gray
      matter and regional white matter of patients with mTBI by using MFC MR imaging;
      and 2) investigate the association of regional brain iron deposition with
      cognitive and behavioral performance of patients with mTBI. MATERIALS AND
      METHODS: We prospectively enrolled 28 patients with mTBI. Eighteen healthy
      subjects served as controls. The subjects were administered the Stroop color word
      test, the Verbal Fluency Task, and the Post-Concussion Symptoms Scale. The MR
      imaging protocol (on a 3T imager) consisted of conventional brain imaging and MFC
      sequences. After the calculation of parametric maps, MFC was measured by using a
      region of interest approach. MFC values across groups were compared by using
      analysis of covariance, and the relationship of MFC values and neuropsychological
      tests were evaluated by using Spearman correlations. RESULTS: Compared with
      controls, patients with mTBI demonstrated significant higher MFC values in the
      globus pallidus (P = .002) and in the thalamus (P = .036). In patients with mTBI,
      Stroop test scores were associated with the MFC value in frontal white matter (r
      = -0.38, P = .043). CONCLUSIONS: MFC values were significantly elevated in the
      thalamus and globus pallidus of patients with mTBI, suggesting increased
      accumulation of iron. This supports the hypothesis that deep gray matter is a
      site of injury in mTBI and suggests a possible role for iron accumulation in the
      pathophysiological events after mTBI.

PMID- 21885719
TI  - Extratemporal damage in temporal lobe epilepsy: magnetization transfer adds
      information to volumetric MR imaging.
AB  - BACKGROUND AND PURPOSE: MTS is characterized by gliosis and atrophy of the
      hippocampus and related limbic structures. However, the damage is not limited to
      those structures with atrophy and has been reported in extratemporal regions.
      Because volumetric studies are nonspecific, the pathophysiology of the brain
      damage remains to be solved. MTI is an MR imaging technique more sensitive to
      subtle neuropathologic changes than conventional MR imaging. Here we combined MTI
      with VBM analysis to evaluate extratemporal damage in patients with TLE.
      MATERIALS AND METHODS: We studied 23 healthy controls and 21 patients with TLE
      with mean ages, respectively, of 37.6 +/- 10.9 and 38.6 +/- 9.02 years. All
      subjects had a full clinical follow-up and MR imaging. We processed the images
      with VBM for volumetric analysis of WM and GM, as well as with voxel-based
      analysis of MTR for macromolecular integrity analysis. RESULTS: In addition to
      MTR decrease in the temporal lobes, we found a significant decrease in GM and WM
      volumes. In the WM, the MTR decrease was correlated to volume loss detected by
      VBM, indicating that brain atrophy may explain part of the MTR decrease. We also
      found areas in which the MTR decrease was not associated with volume loss,
      suggesting an additional pathophysiologic process other than neuronal loss and
      atrophy underlying the MTR changes. CONCLUSIONS: Our results support the
      hypothesis that there are widespread lesions in the brain, including the corpus
      callosum and the frontal lobe, affecting both GM and WM.

PMID- 21885720
TI  - Whole-brain perfusion CT patterns of brain arteriovenous malformations: a pilot
      study in 18 patients.
AB  - BACKGROUND AND PURPOSE: Little is known about the pathological mechanism or the
      anatomic and functional imaging features related to the clinical manifestations
      in patients with brain AVM. The purpose of this pilot study was to describe the
      pattern of whole-brain PCT abnormalities in brain AVMs and their potential to
      differentiate underlying pathomechanisms. MATERIALS AND METHODS: Whole-brain PCT
      performed on a 320-detector row CT scanner was analyzed in 18 patients with
      untreated brain AVMs. The patterns of perfusion abnormalities on CBV, CBF, and
      MTT maps were analyzed and were related to clinical presentation and cerebral
      angiography. RESULTS: The presenting symptoms were seizures (n = 5), focal
      neurologic deficit (n = 5), hemorrhage (n = 4), chemosis (n = 1), and none (n =
      3). Three types of extranidal brain parenchymal perfusion abnormalities were
      noted. Decreased CBF, CBV, and MTT (pattern 1, "functional" arterial steal) were
      identified in 8 patients. Seizure was the most common presenting symptom in these
      patients (n = 5). Decreased CBF and CBV, and increased MTT (pattern 2, "ischemic"
      arterial steal) were noted in 4 patients. Focal neurologic deficit was the most
      common presenting symptom for these patients (n = 3). Increased CBV and MTT
      (pattern 3, venous congestion) were seen in 5 patients with presenting symptoms
      of neurologic deficit (n = 2), seizure (n = 1), hemorrhage (n = 1), and chemosis
      (n = 1). In 2 patients, pre- and posttreatment PCT was performed, which showed
      improvement of perfusion abnormalities. CONCLUSIONS: Whole-brain PCT shows
      different patterns of perfusion abnormalities in patients with brain AVM. These
      perfusion patterns may discriminate the different pathologic mechanisms involved
      in these malformations.

PMID- 21885721
TI  - The role of the pipeline embolization device for the treatment of dissecting
      intracranial aneurysms.
AB  - Intracranial dissecting aneurysms constitute rare lesions with complex management
      and elevated morbidity and mortality. Results of 23 patients harboring such
      lesions treated with the PED are reported. Standard dual antiplatelet therapy was
      instituted. Neurologic and angiographic assessments were obtained at 3, 6, and 12
      months. Clinical presentation included SAH (52%), symptoms of mass effect (22%),
      ischemia (4%), and incidental finding (22%). The posterior circulation was
      affected in 91% of cases. Total occlusion was demonstrated in 69.5% of patients,
      with an increment to 87.5% considering only patients with at least 3 months of
      follow-up. Small aneurysms demonstrated higher rates of total occlusion (6/7)
      compared with large (5/7) and giant (5/9) ones. Good clinical outcome was
      achieved in 74% of patients. Reconstructive endovascular treatment of
      intracranial dissecting aneurysms with the PED provided good clinical and
      angiographic results with acceptable risks, representing an attractive
      therapeutic option for this complex disease, especially when parent vessel
      preservation is mandatory.

PMID- 21885722
TI  - Short- and intermediate-term angiographic and clinical outcomes of patients with
      various grades of coil protrusions following embolization of intracranial
      aneurysms.
AB  - BACKGROUND AND PURPOSE: An infrequent occurrence during endovascular treatment is
      protusion of detachable coils into the parent lumen with a subsequent thrombosis
      within in the parent vessel or embolic events. We report the short- and
      intermediate-term angiographic and clinical outcomes of patients who experience
      coil or loop protrusions and are managed with medical or additional endovascular
      treatments. MATERIALS AND METHODS: The coil protrusions were identified by
      retrospective review of 256 consecutive patients treated at 3 centers with
      endovascular embolizations for intracranial aneurysms and subsequently
      categorized as grade I when a single loop or coil protruded into the parent
      vessel lumen less than half the parent artery diameter; grades II and III were
      assigned when a single coil or loop protruded more than half the parent artery
      diameter, respectively. RESULTS: There were 19 patients with grade I (n = 9),
      grade II (n = 4), or grade III (n = 6) coil protrusions. Patients with active
      hemodynamic compromise (n = 6) had intracranial stents placed in addition to
      aspirin (indefinitely) and clopidogrel (range, 1-12 months; mean, 4.5 months)
      treatment. The remaining patients were placed on aspirin indefinitely. Complete
      aneurysm obliteration was achieved in all patients except in 3 in whom near
      complete obliteration was achieved. Two patients had intraprocedural aneurysm
      ruptures, both of whom survived hospitalization. There were 4 deaths (4-21 days),
      all due to major strokes in different vascular distributions related to vasospasm
      (unrelated to the coil protrusion). CONCLUSIONS: Management of coil protrusions
      with antiplatelet therapy and placement of stents (in selected patients) appears
      efficacious in preventing vessel thrombosis.

PMID- 21885723
TI  - Exercise induces rapid interstitial lung water accumulation in patients with
      chronic mountain sickness.
AB  - BACKGROUND: Chronic mountain sickness (CMS) is a major public health problem in
      mountainous regions of the world. In its more advanced stages, exercise
      intolerance is often found, but the underlying mechanism is not known. Recent
      evidence indicates that exercise-induced pulmonary hypertension is markedly
      exaggerated in CMS. We speculated that this problem may cause pulmonary fluid
      accumulation and aggravate hypoxemia during exercise. METHODS: We assessed
      extravascular lung water (chest ultrasonography), pulmonary artery pressure, and
      left ventricular function in 15 patients with CMS and 20 control subjects at rest
      and during exercise at 3,600 m. RESULTS: Exercise at high altitude rapidly
      induced pulmonary interstitial fluid accumulation in all patients but one (14 of
      15) with CMS and further aggravated the preexisting hypoxemia. In contrast, in
      healthy high-altitude dwellers exercise did not induce fluid accumulation in the
      majority of subjects (16 of 20) (P = .002 vs CMS) and did not alter arterial
      oxygenation. Exercise-induced pulmonary interstitial fluid accumulation and
      hypoxemia in patients with CMS was accompanied by a more than two times larger
      increase of pulmonary artery pressure than in control subjects (P < .001), but no
      evidence of left ventricular dysfunction. Oxygen inhalation markedly attenuated
      the exercise-induced pulmonary hypertension (P < .01) and interstitial fluid
      accumulation (P < .05) in patients with CMS but had no detectable effects in
      control subjects. CONCLUSIONS: To our knowledge, these findings provide the first
      direct evidence that exercise induces rapid interstitial lung fluid accumulation
      and hypoxemia in patients with CMS that appear to be related to exaggerated
      pulmonary hypertension. We suggest that this problem contributes to exercise
      intolerance in patients with CMS. TRIAL REGISTRY: ClinicalTrials.gov; No.:
      NCT01182792; URL: www.clinicaltrials.gov.

PMID- 21885725
TI  - Severity of asthma score predicts clinical outcomes in patients with moderate to
      severe persistent asthma.
AB  - BACKGROUND: The severity of asthma (SOA) score is based on a validated disease
      specific questionnaire that addresses frequency of asthma symptoms, use of
      systemic corticosteroids, use of other asthma medications, and history of
      hospitalization/intubation for asthma. SOA does not require measurements of
      pulmonary function. This study compared the ability of SOA to predict clinical
      outcomes in the EXCELS (Epidemiological Study of Xolair [omalizumab]: Evaluating
      Clinical Effectiveness and Long-term Safety in Patients with Moderate to Severe
      Asthma) patient population vs three other asthma assessment tools. EXCELS is a
      large, ongoing, observational study of patients with moderate to severe
      persistent asthma and reactivity to perennial aeroallergens. METHODS: Baseline
      scores for SOA, asthma control test (ACT), work productivity and impairment index
      asthma (WPAI-A), and FEV(1) % predicted were compared for their ability to
      predict five prespecified adverse clinical outcomes in asthma: serious adverse
      events (SAEs) reported as exacerbations, SAEs leading to hospitalizations, the
      incidence of unscheduled office visits, ED visits, and po or IV corticosteroid
      bursts related to asthma. Logistic regression analysis, area under receiver
      operating characteristic curves (AUCROCs), and classification and regression tree
      (CART) analysis were used to evaluate the ability of the four tools to predict
      adverse clinical outcomes using baseline and 1-year data from 2,878 patients
      enrolled in the non-omalizumab cohort of EXCELS. RESULTS: SOA was the only
      assessment tool contributing significantly in all five statistical models of
      adverse clinical outcomes by logistic regression analysis (full model AUCROC
      range, 0.689-0.783). SOA appeared to be a stand-alone predictor for four of five
      outcomes (reduced model AUCROC range, 0.689-0.773). CART analysis showed that SOA
      had the greatest variable importance for all five outcomes. CONCLUSIONS: SOA
      score was a powerful predictor of adverse clinical outcomes in moderate to severe
      asthma, as evaluated by either logistic regression analysis or CART analysis.
      TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00252135; URL:
      www.clinicaltrials.gov.

PMID- 21885724
TI  - Noninvasive ventilation in mild obesity hypoventilation syndrome: a randomized
      controlled trial.
AB  - OBJECTIVE: Open studies suggest that treatment of obesity hypoventilation
      syndrome (OHS) by noninvasive ventilation (NIV) restores sleep quality and
      daytime vigilance and reduces cardiovascular morbidity. However, to our knowledge
      no randomized controlled trial (RCT) comparing NIV to conservative measures is
      available in the field. The goal of this study was to assess in patients with
      OHS, during an RCT, effects of 1-month NIV compared with lifestyle counseling on
      blood gas measurements, sleep quality, vigilance, and cardiovascular, metabolic,
      and inflammatory parameters. METHODS: Thirty-five patients in whom OHS was newly
      diagnosed were randomized either to the NIV group or the control group
      represented by lifestyle counseling. Assessments included blood gas levels,
      subjective daytime sleepiness, metabolic parameters, inflammatory (hsCRP, leptin,
      regulated upon activation normal T-cell express and secreted [RANTES], monocyte
      chemoattractant protein-1, IL-6, IL-8, tumor necrosis factor-alpha, resistin) and
      antiinflammatory (adiponectin, IL-1-RA) cytokines, sleep studies, endothelial
      function (reactive hyperemia measured by peripheral arterial tonometry [RH-PAT]),
      and arterial stiffness. RESULTS: Despite randomization, NIV group patients (n =
      18) were older (58 +/- 11 years vs 54 +/- 6 years) with a higher baseline Paco(2)
      (47.9 +/- 4.2 mm Hg vs 45.2 +/- 3 mm Hg). In intention-to-treat analysis,
      compared with control group, NIV treatment significantly reduced daytime Paco(2)
      (difference between treatments: -3.5 mm Hg; 95% CI, -6.2 to -0.8) and apnea
      hypopnea index (-40.3/h; 95% CI, -62.4 to -18.2). Sleep architecture was
      restored, although nonrespiratory microarousals increased (+9.4/h of sleep; 95%
      CI, 1.9-16.9), and daytime sleepiness was not completely normalized. Despite a
      dramatic improvement in sleep hypoxemia, glucidic and lipidic metabolism
      parameters as well as cytokine profiles did not vary significantly. Accordingly,
      neither RH-PAT (+0.02; 95% CI, -0.24 to 0.29) nor arterial stiffness (+0.22 m/s;
      95% CI, -1.47 to 1.92) improved. CONCLUSIONS: One month of NIV treatment,
      although improving sleep and blood gas measurements dramatically, did not change
      inflammatory, metabolic, and cardiovascular markers. TRIAL REGISTRY:
      ClinicalTrials.gov; No.: NCT00603096; URL: www.clinicaltrials.gov.

PMID- 21885726
TI  - Severe COPD is correlated with mild radiation pneumonitis following stereotactic
      body radiotherapy.
AB  - BACKGROUND: The primary cause of COPD and lung cancer is smoking. Thus, patients
      with COPD frequently have lung cancer that often is inoperable. Stereotactic body
      radiation therapy (SBRT) is anticipated to be the standard of care for inoperable
      early stage non-small cell lung cancer. The most critical toxicity following SBRT
      is radiation pneumonitis (RP). We analyzed predictive factors for RP following
      SBRT and investigated the degree and occurrence of RP in patients with severe
      COPD. METHODS: We retrospectively evaluated 265 lung tumors treated with SBRT
      between 2005 and 2010 with a minimum follow-up of 6 months. Predictive factors
      for RP, including GOLD (Global Initiative for Chronic Obstructive Lung Disease)
      stage and pack-years smoked, were evaluated by univariate and multivariate
      analyses. RP was graded according to the Common Terminology Criteria for Adverse
      Events version 3.0 scale. RESULTS: Median follow-up was 19.2 months (range, 6.0
      72.0 months). RP grades of 0, 1, 2, 3, 4, and 5 occurred in 101, 102, 49, 12, 0,
      and one of these patients, respectively. Multivariate analysis revealed that high
      normal lung volume receiving >= 20 Gy, fewer pack-years smoked, and high total
      dose were significant predictive factors for RP >= grade 1, and high normal lung
      volume receiving 20 Gy, fewer pack-years smoked, and a history of lung resection
      were predictive for RP >= grade 2. RP in patients with more severe COPD was
      relatively milder than in patients with normal lung function and with mild COPD.
      Pack-year scales were significantly correlated with GOLD stage. CONCLUSIONS: RP
      following SBRT in patients with severe COPD was relatively mild. Heavy smoking
      was the strongest negative predictor for severe RP and was correlated with severe
      COPD. Further follow-up and quantitative analysis of lung function might be
      needed to ascertain longer tolerability to SBRT.

PMID- 21885727
TI  - The burden of disease in pediatric non-cystic fibrosis bronchiectasis.
AB  - BACKGROUND: The burden of disease in children with non-cystic fibrosis (non-CF)
      bronchiectasis is unknown. Our study aimed to identify the determinants of
      quality of life (QOL) and parental mental health in this group of patients and
      their parents and to evaluate the effect of exacerbations on these parameters.
      METHODS: Parents of 69 children (median age 7 years) with non-CF bronchiectasis
      prospectively completed two questionnaires (parent-proxy cough-specific quality
      of life [PC-QOL] and the Depression, Anxiety, and Stress Scale [DASS]) at stable
      and exacerbation states. Data on clinical, investigational, and lung function
      parameters were also collected. RESULTS: During the stable state, the median
      interquartile range (IQR) PC-QOL score was 6.5 (5.3-6.9) and the DASS 21-item
      questionnaire score was 6 (0-20). Being of a young age correlated with a worse
      QOL (r(5) = 0.242, P = .04) but radiologic extent, lung function, underlying
      cause, environmental tobacco smoke exposure, and chronic upper-airway disease did
      not influence these scores. Exacerbations caused significant worsening in the PC
      QOL scores (median [IQR], 4.6 [3.8-5.4]; P = .001) and DASS scores (median [IQR],
      22 [9-42]; P < .001; 38% with elevated anxiety, 54% with abnormal
      depression/stress scores during exacerbation). The presence of viral infection,
      hypoxia, and hospitalization did not influence the exacerbation PC-QOL and DASS
      scores. CONCLUSIONS: There is a significant burden of disease, especially during
      exacerbation, on parents of children with bronchiectasis. Prevention, early
      detection, and appropriate treatment of exacerbations are likely to reduce
      psychologic morbidity in this group.

PMID- 21885728
TI  - Validation of the pulmonary hypertension connection equation for survival
      prediction in pulmonary arterial hypertension.
AB  - OBJECTIVE: The pulmonary hypertension connection (PHC) equation predicts
      contemporary survival in idiopathic, heritable, and anorexigen-associated
      pulmonary arterial hypertension (PAH). The aim of this study is to validate the
      PHC equation in a prospective PAH population cohort and compare its
      predictability with the French equation. METHODS: We compared the rates of actual
      survival in patients prospectively followed for up to 3.5 years in four double
      blind, randomized trials and their open-label extension studies with predicted
      survival calculated using the PHC equation [(P(t) = e((-A(x,y,z)t)), A(x,y,z) =
      e((-1.270-0.0148x + 0.0402y - 0.361z)), where P(t) is the probability of
      survival, t the time interval in years, x the mean pulmonary artery pressure, y
      the mean right atrial pressure, and z the cardiac index] and the French equation
      in patients with idiopathic, heritable, and anorexigen-associated PAH (n = 449).
      RESULTS: Mean age was 44 +/- 15 years, 77% were women, and 80% had World Health
      Organization (WHO) functional class III/IV symptoms. The mean 6-min walk distance
      (6MWD) was 354 +/- 95 m. The baseline hemodynamics were as follows: mean right
      atrial pressure 10 +/- 6 mm Hg, mean pulmonary artery pressure 59 +/- 15 mm Hg,
      and cardiac output 4.1 +/- 1.5 L/min. The 1-, 2-, and 3-year Kaplan-Meier
      survival rates were 89%, 80%, and 70%, respectively; the nonadjusted survival
      rates were 91%, 87%, and 84%, respectively. The expected survival predicted by
      both the PHC and the French equations was similar to the actual observed Kaplan
      Meier survival and was within its 95% confidence limits. The PHC equation also
      performed well when used in patients with WHO functional class III/IV, cardiac
      output < 4 L/min, or 6MWD < 380 m. CONCLUSION: Risk prediction equations (PHC and
      French) accurately predicted survival and may be useful for risk estimation in
      patients with idiopathic, heritable, and anorexigen-associated PAH in large
      cohort studies. Their use for survival prediction for individual patients needs
      further study.

PMID- 21885729
TI  - Optical differentiation between malignant and benign lymphadenopathy by grey
      scale texture analysis of endobronchial ultrasound convex probe images.
AB  - BACKGROUND: Morphologic and sonographic features of endobronchial ultrasound
      (EBUS) convex probe images are helpful in predicting metastatic lymph nodes. Grey
      scale texture analysis is a well-established methodology that has been applied to
      ultrasound images in other fields of medicine. The aim of this study was to
      determine if this methodology could differentiate between benign and malignant
      lymphadenopathy of EBUS images. METHODS: Lymph nodes from digital images of EBUS
      procedures were manually mapped to obtain a region of interest and were analyzed
      in a prediction set. The regions of interest were analyzed for the following grey
      scale texture features in MATLAB (version 7.8.0.347 [R2009a]): mean pixel value,
      difference between maximal and minimal pixel value, SEM pixel value, entropy,
      correlation, energy, and homogeneity. Significant grey scale texture features
      were used to assess a validation set compared with fluoro-D-glucose (FDG)-PET-CT
      scan findings where available. RESULTS: Fifty-two malignant nodes and 48 benign
      nodes were in the prediction set. Malignant nodes had a greater difference in the
      maximal and minimal pixel values, SEM pixel value, entropy, and correlation, and
      a lower energy (P < .0001 for all values). Fifty-one lymph nodes were in the
      validation set; 44 of 51 (86.3%) were classified correctly. Eighteen of these
      lymph nodes also had FDG-PET-CT scan assessment, which correctly classified 14 of
      18 nodes (77.8%), compared with grey scale texture analysis, which correctly
      classified 16 of 18 nodes (88.9%). CONCLUSIONS: Grey scale texture analysis of
      EBUS convex probe images can be used to differentiate malignant and benign
      lymphadenopathy. Preliminary results are comparable to FDG-PET-CT scan.

PMID- 21885730
TI  - ER tubules mark sites of mitochondrial division.
AB  - Mitochondrial structure and distribution are regulated by division and fusion
      events. Mitochondrial division is regulated by Dnm1/Drp1, a dynamin-related
      protein that forms helices around mitochondria to mediate fission. Little is
      known about what determines sites of mitochondrial fission within the
      mitochondrial network. The endoplasmic reticulum (ER) and mitochondria exhibit
      tightly coupled dynamics and have extensive contacts. We tested whether ER plays
      a role in mitochondrial division. We found that mitochondrial division occurred
      at positions where ER tubules contacted mitochondria and mediated constriction
      before Drp1 recruitment. Thus, ER tubules may play an active role in defining the
      position of mitochondrial division sites.

PMID- 21885731
TI  - Linking long-term dietary patterns with gut microbial enterotypes.
AB  - Diet strongly affects human health, partly by modulating gut microbiome
      composition. We used diet inventories and 16S rDNA sequencing to characterize
      fecal samples from 98 individuals. Fecal communities clustered into enterotypes
      distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were
      strongly associated with long-term diets, particularly protein and animal fat
      (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10
      subjects showed that microbiome composition changed detectably within 24 hours of
      initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype
      identity remained stable during the 10-day study. Thus, alternative enterotype
      states are associated with long-term diet.

PMID- 21885732
TI  - Implementing the quantum von Neumann architecture with superconducting circuits.
AB  - The von Neumann architecture for a classical computer comprises a central
      processing unit and a memory holding instructions and data. We demonstrate a
      quantum central processing unit that exchanges data with a quantum random-access
      memory integrated on a chip, with instructions stored on a classical computer. We
      test our quantum machine by executing codes that involve seven quantum elements:
      Two superconducting qubits coupled through a quantum bus, two quantum memories,
      and two zeroing registers. Two vital algorithms for quantum computing are
      demonstrated, the quantum Fourier transform, with 66% process fidelity, and the
      three-qubit Toffoli-class OR phase gate, with 98% phase fidelity. Our results, in
      combination especially with longer qubit coherence, illustrate a potentially
      viable approach to factoring numbers and implementing simple quantum error
      correction codes.

PMID- 21885733
TI  - Light propagation with phase discontinuities: generalized laws of reflection and
      refraction.
AB  - Conventional optical components rely on gradual phase shifts accumulated during
      light propagation to shape light beams. New degrees of freedom are attained by
      introducing abrupt phase changes over the scale of the wavelength. A two
      dimensional array of optical resonators with spatially varying phase response and
      subwavelength separation can imprint such phase discontinuities on propagating
      light as it traverses the interface between two media. Anomalous reflection and
      refraction phenomena are observed in this regime in optically thin arrays of
      metallic antennas on silicon with a linear phase variation along the interface,
      which are in excellent agreement with generalized laws derived from Fermat's
      principle. Phase discontinuities provide great flexibility in the design of light
      beams, as illustrated by the generation of optical vortices through use of planar
      designer metallic interfaces.

PMID- 21885734
TI  - Glutamatergic and dopaminergic neurons mediate anxiogenic and anxiolytic effects
      of CRHR1.
AB  - The corticotropin-releasing hormone receptor 1 (CRHR1) critically controls
      behavioral adaptation to stress and is causally linked to emotional disorders.
      Using neurochemical and genetic tools, we determined that CRHR1 is expressed in
      forebrain glutamatergic and gamma-aminobutyric acid-containing (GABAergic)
      neurons as well as in midbrain dopaminergic neurons. Via specific CRHR1 deletions
      in glutamatergic, GABAergic, dopaminergic, and serotonergic cells, we found that
      the lack of CRHR1 in forebrain glutamatergic circuits reduces anxiety and impairs
      neurotransmission in the amygdala and hippocampus. Selective deletion of CRHR1 in
      midbrain dopaminergic neurons increases anxiety-like behavior and reduces
      dopamine release in the prefrontal cortex. These results define a bidirectional
      model for the role of CRHR1 in anxiety and suggest that an imbalance between
      CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems
      might lead to emotional disorders.

PMID- 21885735
TI  - Universal digital quantum simulation with trapped ions.
AB  - A digital quantum simulator is an envisioned quantum device that can be
      programmed to efficiently simulate any other local system. We demonstrate and
      investigate the digital approach to quantum simulation in a system of trapped
      ions. With sequences of up to 100 gates and 6 qubits, the full time dynamics of a
      range of spin systems are digitally simulated. Interactions beyond those
      naturally present in our simulator are accurately reproduced, and quantitative
      bounds are provided for the overall simulation quality. Our results demonstrate
      the key principles of digital quantum simulation and provide evidence that the
      level of control required for a full-scale device is within reach.

PMID- 21885736
TI  - Functional specificity for high-level linguistic processing in the human brain.
AB  - Neuroscientists have debated for centuries whether some regions of the human
      brain are selectively engaged in specific high-level mental functions or whether,
      instead, cognition is implemented in multifunctional brain regions. For the
      critical case of language, conflicting answers arise from the neuropsychological
      literature, which features striking dissociations between deficits in linguistic
      and nonlinguistic abilities, vs. the neuroimaging literature, which has argued
      for overlap between activations for linguistic and nonlinguistic processes,
      including arithmetic, domain general abilities like cognitive control, and music.
      Here, we use functional MRI to define classic language regions functionally in
      each subject individually and then examine the response of these regions to the
      nonlinguistic functions most commonly argued to engage these regions: arithmetic,
      working memory, cognitive control, and music. We find little or no response in
      language regions to these nonlinguistic functions. These data support a clear
      distinction between language and other cognitive processes, resolving the prior
      conflict between the neuropsychological and neuroimaging literatures.

PMID- 21885737
TI  - "Eppur si muove" (Yet it moves).

PMID- 21885738
TI  - Randomized approximate nearest neighbors algorithm.
AB  - We present a randomized algorithm for the approximate nearest neighbor problem in
      d-dimensional Euclidean space. Given N points {x(j)} in R(d), the algorithm
      attempts to find k nearest neighbors for each of x(j), where k is a user
      specified integer parameter. The algorithm is iterative, and its running time
      requirements are proportional to T.N.(d.(log d) + k.(d + log k).(log N)) +
      N.k(2).(d + log k), with T the number of iterations performed. The memory
      requirements of the procedure are of the order N.(d + k). A by-product of the
      scheme is a data structure, permitting a rapid search for the k nearest neighbors
      among {x(j)} for an arbitrary point x ? R(d). The cost of each such query is
      proportional to T.(d.(log d) + log(N/k).k.(d + log k)), and the memory
      requirements for the requisite data structure are of the order N.(d + k) + T.(d +
      N). The algorithm utilizes random rotations and a basic divide-and-conquer
      scheme, followed by a local graph search. We analyze the scheme's behavior for
      certain types of distributions of {x(j)} and illustrate its performance via
      several numerical examples.

PMID- 21885740
TI  - A grand challenge in biology.

PMID- 21885739
TI  - Structure-based discovery of prescription drugs that interact with the
      norepinephrine transporter, NET.
AB  - The norepinephrine transporter (NET) transports norepinephrine from the synapse
      into presynaptic neurons, where norepinephrine regulates signaling pathways
      associated with cardiovascular effects and behavioral traits via binding to
      various receptors (e.g., beta2-adrenergic receptor). NET is a known target for a
      variety of prescription drugs, including antidepressants and psychostimulants,
      and may mediate off-target effects of other prescription drugs. Here, we identify
      prescription drugs that bind NET, using virtual ligand screening followed by
      experimental validation of predicted ligands. We began by constructing a
      comparative structural model of NET based on its alignment to the atomic
      structure of a prokaryotic NET homolog, the leucine transporter LeuT. The modeled
      binding site was validated by confirming that known NET ligands can be docked
      favorably compared to nonbinding molecules. We then computationally screened
      6,436 drugs from the Kyoto Encyclopedia of Genes and Genomes (KEGG DRUG) against
      the NET model. Ten of the 18 high-scoring drugs tested experimentally were found
      to be NET inhibitors; five of these were chemically novel ligands of NET. These
      results may rationalize the efficacy of several sympathetic (tuaminoheptane) and
      antidepressant (tranylcypromine) drugs, as well as side effects of diabetes
      (phenformin) and Alzheimer's (talsaclidine) drugs. The observations highlight the
      utility of virtual screening against a comparative model, even when the target
      shares less than 30% sequence identity with its template structure and no known
      ligands in the primary binding site.

PMID- 21885746
TI  - Solar system dynamics. Mystery Pioneer anomaly is real but still a mystery.

PMID- 21885745
TI  - Space. NASA to launch guidelines to protect lunar artifacts.

PMID- 21885747
TI  - Extreme ecosystems. Biological dark matter exerts irresistible pull in Yunnan.

PMID- 21885748
TI  - Ecology. China aims to turn tide against toxic lake pollution.

PMID- 21885749
TI  - Human subjects research. Panel blasts ethics, science of 1940s Guatemala studies.

PMID- 21885750
TI  - Neuroscience. Sweet here, salty there: evidence for a taste map in the mammalian
      brain.

PMID- 21885752
TI  - Biodefense: 10 years after. Reinventing Project BioShield.

PMID- 21885751
TI  - Taking stock of the biodefense boom.

PMID- 21885754
TI  - Biodefense: 10 years after. Helping Hollywood create and battle a pandemic.
      Interview by Jon Cohen.

PMID- 21885755
TI  - Education research: set a high bar.

PMID- 21885756
TI  - Education research: call for controls.

PMID- 21885757
TI  - Retraction.

PMID- 21885760
TI  - Nuclear policy. The overlooked back end of the nuclear fuel cycle.

PMID- 21885758
TI  - Comment on "Additive genetic breeding values correlate with the load of partially
      deleterious mutations".
AB  - Tomkins et al. (Reports, 14 May 2010, p. 892) reported a strong negative
      correlation between breeding values and mutational load in cow-pea weevils. Here,
      I show that this result can be attributed to a statistical artifact. By testing
      the observed correlation against an incorrect null hypothesis, they find a
      negative correlation where one does not exist.

PMID- 21885761
TI  - Astronomy. Let there be dust.

PMID- 21885762
TI  - Physics. Switching light by vacuum.

PMID- 21885763
TI  - Molecular biology. Demystifying DNA demethylation.

PMID- 21885764
TI  - Materials science. Through thick and thin.

PMID- 21885765
TI  - Ecology. Food and biodiversity.

PMID- 21885766
TI  - Retrospective. John Harmen Marburger III (1941-2011).

PMID- 21885767
TI  - Synthetic biology. The allure of synthetic biology. Introduction.

PMID- 21885768
TI  - The life hacker.

PMID- 21885769
TI  - Algae's second try.

PMID- 21885770
TI  - A lab of their own.

PMID- 21885771
TI  - Visions of synthetic biology.

PMID- 21885772
TI  - Synthetic biology: integrated gene circuits.
AB  - A major goal of synthetic biology is to develop a deeper understanding of
      biological design principles from the bottom up, by building circuits and
      studying their behavior in cells. Investigators initially sought to design
      circuits "from scratch" that functioned as independently as possible from the
      underlying cellular system. More recently, researchers have begun to develop a
      new generation of synthetic circuits that integrate more closely with endogenous
      cellular processes. These approaches are providing fundamental insights into the
      regulatory architecture, dynamics, and evolution of genetic circuits and enabling
      new levels of control across diverse biological systems.

PMID- 21885773
TI  - Synthetic biology moving into the clinic.
AB  - Synthetic biology is an emerging field focused on engineering biomolecular
      systems and cellular capabilities for a variety of applications. Substantial
      progress began a little over a decade ago with the creation of synthetic gene
      networks inspired by electrical engineering. Since then, the field has designed
      and built increasingly complex circuits and constructs and begun to use these
      systems in a variety of settings, including the clinic. These efforts include the
      development of synthetic biology therapies for the treatment of infectious
      diseases and cancer, as well as approaches in vaccine development, microbiome
      engineering, cell therapy, and regenerative medicine. Here, we highlight advances
      in the biomedical application of synthetic biology and discuss the field's
      clinical potential.

PMID- 21885774
TI  - Bottom-up synthetic biology: engineering in a tinkerer's world.
AB  - How synthetic can "synthetic biology" be? A literal interpretation of the name of
      this new life science discipline invokes expectations of the systematic
      construction of biological systems with cells being built module by module--from
      the bottom up. But can this possibly be achieved, taking into account the
      enormous complexity and redundancy of living systems, which distinguish them
      quite remarkably from design features that characterize human inventions? There
      are several recent developments in biology, in tight conjunction with
      quantitative disciplines, that may bring this literal perspective into the realm
      of the possible. However, such bottom-up engineering requires tools that were
      originally designed by nature's greatest tinkerer: evolution.

PMID- 21885775
TI  - Synthetic biology: regulating industry uses of new biotechnologies.
AB  - In our view, synthetic biology is an extension of the continuum of genetic
      science that has been used safely for more than 40 years by the biotechnology
      industry in the development of commercial products. Examples of synthetic biology
      use by biotechnology companies illustrate the potential to substantially reduce
      research and development time and to increase speed to market. Improvements in
      the speed and cost of DNA synthesis are enabling scientists to design modified
      bacterial chromosomes that can be used in the production of renewable chemicals,
      biofuels, bioproducts, renewable specialty chemicals, pharmaceutical
      intermediates, fine chemicals, food ingredients, and health care products.
      Regulatory options should support innovation and commercial development of new
      products while protecting the public from potential harms.

PMID- 21885777
TI  - Femtoscale magnetically induced lattice distortions in multiferroic TbMnO3.
AB  - Magneto-electric multiferroics exemplified by TbMnO(3) possess both magnetic and
      ferroelectric long-range order. The magnetic order is mostly understood, whereas
      the nature of the ferroelectricity has remained more elusive. Competing models
      proposed to explain the ferroelectricity are associated respectively with charge
      transfer and ionic displacements. Exploiting the magneto-electric coupling, we
      used an electric field to produce a single magnetic domain state, and a magnetic
      field to induce ionic displacements. Under these conditions, interference between
      charge and magnetic x-ray scattering arose, encoding the amplitude and phase of
      the displacements. When combined with a theoretical analysis, our data allow us
      to resolve the ionic displacements at the femtoscale, and show that such
      displacements make a substantial contribution to the zero-field ferroelectric
      moment.

PMID- 21885776
TI  - A gustotopic map of taste qualities in the mammalian brain.
AB  - The taste system is one of our fundamental senses, responsible for detecting and
      responding to sweet, bitter, umami, salty, and sour stimuli. In the tongue, the
      five basic tastes are mediated by separate classes of taste receptor cells each
      finely tuned to a single taste quality. We explored the logic of taste coding in
      the brain by examining how sweet, bitter, umami, and salty qualities are
      represented in the primary taste cortex of mice. We used in vivo two-photon
      calcium imaging to demonstrate topographic segregation in the functional
      architecture of the gustatory cortex. Each taste quality is represented in its
      own separate cortical field, revealing the existence of a gustotopic map in the
      brain. These results expose the basic logic for the central representation of
      taste.

PMID- 21885778
TI  - Imaging the microscopic structure of shear thinning and thickening colloidal
      suspensions.
AB  - The viscosity of colloidal suspensions varies with shear rate, an important
      effect encountered in many natural and industrial processes. Although this non
      Newtonian behavior is believed to arise from the arrangement of suspended
      particles and their mutual interactions, microscopic particle dynamics are
      difficult to measure. By combining fast confocal microscopy with simultaneous
      force measurements, we systematically investigate a suspension's structure as it
      transitions through regimes of different flow signatures. Our measurements of the
      microscopic single-particle dynamics show that shear thinning results from the
      decreased relative contribution of entropic forces and that shear thickening
      arises from particle clustering induced by hydrodynamic lubrication forces. This
      combination of techniques illustrates an approach that complements current
      methods for determining the microscopic origins of non-Newtonian flow behavior in
      complex fluids.

PMID- 21885779
TI  - Traffic jams reduce hydrolytic efficiency of cellulase on cellulose surface.
AB  - A deeper mechanistic understanding of the saccharification of cellulosic biomass
      could enhance the efficiency of biofuels development. We report here the real
      time visualization of crystalline cellulose degradation by individual cellulase
      enzymes through use of an advanced version of high-speed atomic force microscopy.
      Trichoderma reesei cellobiohydrolase I (TrCel7A) molecules were observed to slide
      unidirectionally along the crystalline cellulose surface but at one point
      exhibited collective halting analogous to a traffic jam. Changing the crystalline
      polymorphic form of cellulose by means of an ammonia treatment increased the
      apparent number of accessible lanes on the crystalline surface and consequently
      the number of moving cellulase molecules. Treatment of this bulky crystalline
      cellulose simultaneously or separately with T. reesei cellobiohydrolase II
      (TrCel6A) resulted in a remarkable increase in the proportion of mobile enzyme
      molecules on the surface. Cellulose was completely degraded by the synergistic
      action between the two enzymes.

PMID- 21885780
TI  - Out of Tibet: Pliocene woolly rhino suggests high-plateau origin of Ice Age
      megaherbivores.
AB  - Ice Age megafauna have long been known to be associated with global cooling
      during the Pleistocene, and their adaptations to cold environments, such as large
      body size, long hair, and snow-sweeping structures, are best exemplified by the
      woolly mammoths and woolly rhinos. These traits were assumed to have evolved as a
      response to the ice sheet expansion. We report a new Pliocene mammal assemblage
      from a high-altitude basin in the western Himalayas, including a primitive woolly
      rhino. These new Tibetan fossils suggest that some megaherbivores first evolved
      in Tibet before the beginning of the Ice Age. The cold winters in high Tibet
      served as a habituation ground for the megaherbivores, which became preadapted
      for the Ice Age, successfully expanding to the Eurasian mammoth steppe.

PMID- 21885781
TI  - Reconciling food production and biodiversity conservation: land sharing and land
      sparing compared.
AB  - The question of how to meet rising food demand at the least cost to biodiversity
      requires the evaluation of two contrasting alternatives: land sharing, which
      integrates both objectives on the same land; and land sparing, in which high
      yield farming is combined with protecting natural habitats from conversion to
      agriculture. To test these alternatives, we compared crop yields and densities of
      bird and tree species across gradients of agricultural intensity in southwest
      Ghana and northern India. More species were negatively affected by agriculture
      than benefited from it, particularly among species with small global ranges. For
      both taxa in both countries, land sparing is a more promising strategy for
      minimizing negative impacts of food production, at both current and anticipated
      future levels of production.

PMID- 21885782
TI  - Chemical and genetic engineering of selective ion channel-ligand interactions.
AB  - Ionic flux mediates essential physiological and behavioral functions in defined
      cell populations. Cell type-specific activators of diverse ionic conductances are
      needed for probing these effects. We combined chemistry and protein engineering
      to enable the systematic creation of a toolbox of ligand-gated ion channels
      (LGICs) with orthogonal pharmacologic selectivity and divergent functional
      properties. The LGICs and their small-molecule effectors were able to activate a
      range of ionic conductances in genetically specified cell types. LGICs
      constructed for neuronal perturbation could be used to selectively manipulate
      neuron activity in mammalian brains in vivo. The diversity of ion channel tools
      accessible from this approach will be useful for examining the relationship
      between neuronal activity and animal behavior, as well as for cell biological and
      physiological applications requiring chemical control of ion conductance.

PMID- 21885784
TI  - Multi-input RNAi-based logic circuit for identification of specific cancer cells.
AB  - Engineered biological systems that integrate multi-input sensing, sophisticated
      information processing, and precisely regulated actuation in living cells could
      be useful in a variety of applications. For example, anticancer therapies could
      be engineered to detect and respond to complex cellular conditions in individual
      cells with high specificity. Here, we show a scalable
      transcriptional/posttranscriptional synthetic regulatory circuit--a cell-type
      "classifier"--that senses expression levels of a customizable set of endogenous
      microRNAs and triggers a cellular response only if the expression levels match a
      predetermined profile of interest. We demonstrate that a HeLa cancer cell
      classifier selectively identifies HeLa cells and triggers apoptosis without
      affecting non-HeLa cell types. This approach also provides a general platform for
      programmed responses to other complex cell states.

PMID- 21885785
TI  - Epigenetic licensing of germline gene expression by maternal RNA in C. elegans.
AB  - RNA can act as a regulator of gene expression with roles in transposon silencing,
      antiviral defense, and cell fate determination. Here, we show that in
      Caenorhabditis elegans a maternal transcript of the sex-determining gene fem-1 is
      required to license expression of a wild-type fem-1 allele in the zygotic germ
      line. Females homozygous for fem-1 deletions produce heterozygous offspring
      exhibiting germline feminization, reduced fem-1 activity, and transcript
      accumulation. Injection of fem-1 RNA incapable of encoding a protein into the
      maternal germ line rescues this defect in the progeny. The defect in zygotic fem
      1 expression is heritable, suggesting that the gene is subject to epigenetic
      silencing that is prevented by maternal fem-1 transcripts. This mechanism may
      contribute to protecting the identity and integrity of the germ line.

PMID- 21885786
TI  - Entrainment of a population of synthetic genetic oscillators.
AB  - Biological clocks are self-sustained oscillators that adjust their phase to the
      daily environmental cycles in a process known as entrainment. Molecular
      dissection and mathematical modeling of biological oscillators have progressed
      quite far, but quantitative insights on the entrainment of clocks are relatively
      sparse. We simultaneously tracked the phases of hundreds of synthetic genetic
      oscillators relative to a common external stimulus to map the entrainment regions
      predicted by a detailed model of the clock. Synthetic oscillators were frequency
      locked in wide intervals of the external period and showed higher-order
      resonance. Computational simulations indicated that natural oscillators may
      contain a positive-feedback loop to robustly adapt to environmental cycles.

PMID- 21885783
TI  - Potential for chemolithoautotrophy among ubiquitous bacteria lineages in the dark
      ocean.
AB  - Recent studies suggest that unidentified prokaryotes fix inorganic carbon at
      globally significant rates in the immense dark ocean. Using single-cell sorting
      and whole-genome amplification of prokaryotes from two subtropical gyres, we
      obtained genomic DNA from 738 cells representing most cosmopolitan lineages.
      Multiple cells of Deltaproteobacteria cluster SAR324, Gammaproteobacteria
      clusters ARCTIC96BD-19 and Agg47, and some Oceanospirillales from the lower
      mesopelagic contained ribulose-1,5-bisphosphate carboxylase-oxygenase and sulfur
      oxidation genes. These results corroborated community DNA and RNA profiling from
      diverse geographic regions. The SAR324 genomes also suggested C(1) metabolism and
      a particle-associated life-style. Microautoradiography and fluorescence in situ
      hybridization confirmed bicarbonate uptake and particle association of SAR324
      cells. Our study suggests potential chemolithoautotrophy in several uncultured
      Proteobacteria lineages that are ubiquitous in the dark oxygenated ocean and
      provides new perspective on carbon cycling in the ocean's largest habitat.

PMID- 21885787
TI  - Serum bicarbonate and mortality in stage 3 and stage 4 chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: The incidence and prevalence of metabolic acidosis
      increase with declining kidney function. We studied the associations of both low
      and high serum bicarbonate levels with all-cause mortality among stage 3 and 4
      chronic kidney disease (CKD) patients. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We examined factors associated with low (<23 mmol/L) and high (>32
      mmol/L) serum bicarbonate levels using logistic regression models and
      associations between bicarbonate and all-cause mortality using Cox-proportional
      hazard models, Kaplan-Meier survival curves, and time-dependent analysis.
      RESULTS: Out of 41,749 patients, 13.9% (n = 5796) had low and 1.6% (n = 652) had
      high serum bicarbonate levels. After adjusting for relevant covariates, there was
      a significant association between low serum bicarbonate and all-cause mortality
      (hazard ratio [HR] 1.23, 95% CI 1.16, 1.31). This association was not
      statistically significant among patients with stage 4 CKD and diabetes. The time
      dependent analysis demonstrated a significant mortality risk associated with a
      decline from normal to low bicarbonate level (HR 1.59, 95% CI 1.49, 1.69). High
      serum bicarbonate levels were associated with death irrespective of the level of
      kidney function (HR 1.74, 95% CI 1.52, 2.00). When serum bicarbonate was examined
      as a continuous variable, a J-shaped relationship was noted between serum
      bicarbonate and mortality. CONCLUSIONS: Low serum bicarbonate levels are
      associated with increased mortality among stage 3 CKD patients and patients
      without diabetes. High serum bicarbonate levels are associated with mortality in
      both stage 3 and stage 4 CKD patients.

PMID- 21885788
TI  - Hemodialysis treatment time: a fresh perspective.
AB  - Historical, clinical, economic, and technological developments have driven a
      shift in clinical practice from predominantly 6-hour-long hemodialysis treatments
      to much shorter treatment times that are prevalent today. Patients, physicians,
      and providers had considered shortening dialysis treatments as a means to
      decrease the overall burden imposed by this necessary life-saving therapy.
      However, shorter dialysis is not a panacea and may engender trade-offs in terms
      of patient morbidity and mortality. We examine the literature with the benefit of
      hindsight and in light of recent studies that have improved understanding of the
      complex relationship between dialysis dose and outcome. We touch upon the role of
      dialysis frequency relative to treatment time. We conclude with the suggestion
      that a new treatment paradigm should consider a minimum adequate dialysis
      treatment time of 4 hours for the majority of patients, with anything shorter
      becoming the exception rather than the rule.

PMID- 21885789
TI  - Urinary hepcidin-25 and risk of acute kidney injury following cardiopulmonary
      bypass.
AB  - BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) complicating cardiopulmonary
      bypass (CPB) results in increased morbidity and mortality. Urinary hepcidin-25
      has been shown to be elevated in patients who do not develop AKI after CPB using
      semiquantitative mass spectrometry (SELDI TOF-MS). The goals of this study were
      to quantitatively validate these findings with ELISA and evaluate the diagnostic
      performance of hepcidin-25 for AKI. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: A nested, case-control analysis of urinary hepcidin-25 in AKI (n =
      22) and non-AKI (n = 22) patients was conducted to validate the SELDI TOF-MS data
      at the following times: preoperatively; the start of CPB; 1 hour on CPB; on
      arrival to the intensive care unit; and postoperative days (POD) 1 and 3 to 5.
      The diagnostic performance of hepcidin-25 was then evaluated in the entire
      prospective observational cohort (n = 338) at POD 1. AKI was defined as Cr >50%
      from baseline, within 72 hours postoperatively. RESULTS: Urinary hepcidin-25/Cr
      ratio was significantly elevated in all patients at POD 1 compared with baseline
      (P < 0.0005) and was also significantly elevated in non-AKI versus AKI patients
      at POD 1 (P < 0.0005). Increased log(10) hepcidin-25/Cr ratio was strongly
      associated with avoidance of AKI on univariate analysis. On multivariate
      analysis, the log(10) hepcidin-25/Cr ratio (P < 0.0001) was associated with
      avoidance of AKI with an area under the curve of 0.80, sensitivity 0.68,
      specificity 0.68, and negative predictive value 0.96. CONCLUSIONS: Elevated
      urinary hepcidin-25 on POD 1 is a strong predictor of avoidance of AKI beyond
      postoperative day 1.

PMID- 21885790
TI  - Skin autofluorescence and the association with renal and cardiovascular risk
      factors in chronic kidney disease stage 3.
AB  - BACKGROUND AND OBJECTIVES: Tissue advanced glycation end products (AGE)
      accumulation is a measure of cumulative metabolic stress. Assessment of tissue
      AGE by skin autofluorescence (SAF) correlates well with cardiovascular (CV)
      outcomes in diabetic, transplant, and dialysis patients, and may be a useful
      marker of CV risk in earlier stages of chronic kidney disease (CKD). DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: 1707 patients with estimated GFR 59 to 30
      ml/min per 1.73 m(2) were recruited from primary care practices for the Renal
      Risk In Derby (RRID) study. Detailed medical history was obtained, and each
      participant underwent clinical assessment as well as urine and serum biochemistry
      tests. SAF was assessed (mean of three readings) as a measure of skin AGE
      deposition using a cutaneous AF device (AGE ReaderTM, DiagnOptics, Groningen, The
      Netherlands). RESULTS: Univariate analysis revealed significant correlations
      between AF readings and several potential risk factors for cardiovascular disease
      (CVD) and progression of CKD. SAF readings (arbitrary units) were also
      significantly higher among males (2.8 +/- 0.7 versus 2.7 +/- 0.6), diabetics (3.0
      +/- 0.7 versus 2.7 +/- 0.6), patients with evidence of self-reported CVD (2.9 +/-
      0.7 versus 2.7 +/- 0.6), and those with no formal educational qualifications (2.8
      +/- 0.6 versus 2.6 +/- 0.6; P < 0.01 for all). Multivariable linear regression
      analysis identified hemoglobin, diabetes, age, and eGFR as the most significant
      independent determinants of higher SAF (standardized coefficients -0.16, 0.13,
      0.12, and -0.10, respectively; R(2) = 0.17 for equation). CONCLUSION: Increased
      SAF is independently associated with multiple CV and renal risk factors in CKD 3.
      Long-term follow-up will assess the value of SAF as a predictor of CV and renal
      risk in this population.

PMID- 21885791
TI  - The use of the Oxford classification of IgA nephropathy to predict renal
      survival.
AB  - BACKGROUND AND OBJECTIVES: A new classification for IgA nephropathy was recently
      proposed, namely the Oxford classification. It established specific pathologic
      features that predict the risk of progression of renal disease. This
      classification needs validation in different patient populations. We propose a
      retrospective study to evaluate the predictive value of the Oxford classification
      on renal survival defined by doubling creatinine or end-stage renal disease in
      patients with IgA nephropathy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We
      included 183 patients with primary IgA nephropathy diagnosed between 1994 and
      2005. Mean follow-up time was 77 months. Doubling creatinine occurred in 20% of
      the patients, and end-stage renal disease occurred in 16%. The biopsies were
      revisited to apply the Oxford classification. The influence of pathologic
      features on renal survival was analyzed in univariate and multivariate models.
      RESULTS: In univariate time-dependent analyses, tubular atrophy/interstitial
      fibrosis, segmental glomerulosclerosis, and endocapillary hypercellularity
      strongly impacted doubling creatinine or end-stage renal disease. On the
      contrary, mesangial hypercellularity was not associated with renal outcome. In
      the multivariate model, only estimated GFR at baseline was a risk factor,
      pathologic lesions having no independent influence. CONCLUSIONS: We confirm the
      usefulness of the Oxford classification to establish the renal prognosis of
      patients with IgA nephropathy, although renal function at baseline seems to be of
      a greater importance than pathologic lesions.

PMID- 21885792
TI  - Urinary calprotectin and the distinction between prerenal and intrinsic acute
      kidney injury.
AB  - BACKGROUND AND OBJECTIVES: To date there is no reliable marker for the
      differentiation of prerenal and intrinsic acute kidney injury (AKI). We
      investigated whether urinary calprotectin, a mediator protein of the innate
      immune system, may serve as a diagnostic marker in AKI. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: This was a cross-sectional study with 101 subjects
      including 86 patients with AKI (34 prerenal, 52 intrinsic including 23 patients
      with urinary tract infection) and 15 healthy controls. Assessment of urinary
      calprotectin concentration was by ELISA and immunohistochemistry of kidney biopsy
      specimens using a calprotectin antibody. Inclusion criteria were: admission to
      hospital for AKI stage 1 to 3 (Acute Kidney Injury Network); exclusion criteria
      were: prior renal transplantation and obstructive uropathy. RESULTS: Median
      urinary calprotectin was 60.7 times higher in intrinsic AKI (1692 ng/ml) than in
      prerenal AKI (28 ng/ml, p <0.01). Urinary calprotectin in prerenal disease was
      not significantly different from healthy controls (45 ng/ml, p = 0.25). Receiver
      operating curve curve analysis revealed a high accuracy of calprotectin (area
      under the curve, 0.97) in predicting intrinsic AKI. A cutoff level of 300 ng/ml
      provided a sensitivity of 92.3% and a specificity of 97.1%. Calculating urinary
      calprotectin/creatinine ratios did not lead to a further increase of accuracy.
      Immunostainings of kidney biopsies were positive for calprotectin in intrinsic
      AKI and negative in prerenal AKI. CONCLUSIONS: Accuracy of urinary calprotectin
      in the differential diagnosis of AKI is high. Whereas calprotectin levels in
      prerenal disease are comparable with healthy controls, intrinsic AKI leads to
      highly increased calprotectin concentrations.

PMID- 21885793
TI  - Urine volume and change in estimated GFR in a community-based cohort study.
AB  - BACKGROUND AND OBJECTIVES: The effect of increased fluid intake on kidney
      function is unclear. This study evaluates the relationship between urine volume
      and renal decline over 6 years in a large community-based cohort. DESIGN,
      SETTING, PARTICIPANTS, & MEASUREMENTS: This prospective cohort study was
      undertaken in Canada from 2002 to 2008. We obtained 24-hour urine samples from
      adult participants with an estimated GFR (eGFR) >=60 ml/min per 1.73 m(2) at
      study entry. Percentage annual change in eGFR from baseline was categorized as
      average decline <1% per year, between 1% and 4.9% (mild-to-moderate decline) or
      >=5% (rapid decline). RESULTS: 2148 participants provided valid 24-hour urine
      samples, grouped as <1 L/d (14.5%); 1 to 1.9 L/d (51.5%); 2 to 2.9 L/d (26.3%);
      and >=3 L/d (7.7%). Baseline eGFR for each category of urine volume was 90, 88,
      84, and 87 ml/min per 1.73 m(2), respectively. Overall, eGFR declined by 1% per
      year, with 10% demonstrating rapid decline and 40% demonstrating mild-to-moderate
      decline. An inverse, graded relationship was evident between urine volume and
      eGFR decline: For each increasing category of 24-hour urine volume, percentage
      annual eGFR decline was progressively slower, from 1.3%, 1.0%, 0.8%, to 0.5%,
      respectively; P = 0.02. Compared with those with urine volume 1 to 1.9 L/d, those
      with urine volume >=3 L/d were significantly less likely to demonstrate mild-to
      moderate decline (adjusted odds ratio 0.66; 95% confidence interval 0.46 to 0.94)
      or rapid decline (adjusted odds ratio 0.46; 95% confidence interval 0.23 to
      0.92); adjusted for age, gender, baseline eGFR, medication use for hypertension
      (including diuretics), proteinuria, diabetes, and cardiovascular disease.
      CONCLUSIONS: In this community-based cohort, decline in kidney function was
      significantly slower in those with higher versus lower urine volume.

PMID- 21885794
TI  - Cigarette smoking and the association with glomerular hyperfiltration and
      proteinuria in healthy middle-aged men.
AB  - BACKGROUND AND OBJECTIVES: Glomerular hyperfiltration and albuminuria accompanied
      by early-stage diabetic kidney disease predict future renal failure. Cigarette
      smoking has reported to be associated with elevated GFR in cross-sectional
      studies and with renal deterioration in longitudinal studies. The degree of
      glomerular hyperfiltration and proteinuria associated with smoking, which
      presumably is a phenomenon of early renal damage, has not been investigated in a
      satisfying manner so far. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This
      study included 10,118 Japanese men aged 40 to 55 years without proteinuria or
      renal dysfunction at entry. Estimated GFR was calculated using the Modification
      of Diet in Renal Disease equation for Japanese. Glomerular hyperfiltration was
      defined as estimated GFR >=117.0 ml/min per 1.73 m(2), which was the upper 2.5th
      percentile value of estimated GFR in the total population. Proteinuria was
      detected using standard dipstick. RESULTS: During the 6-year observation period,
      there were 449 incident cases of glomerular hyperfiltration and 1653 cases of
      proteinuria. Current smokers had a 1.32-time higher risk for the development of
      glomerular hyperfiltration and a 1.51-time higher risk for proteinuria than
      nonsmokers after adjustment for baseline age, body mass index, systolic and
      diastolic BP, antihypertensive medication, diabetes, alcohol consumption, regular
      leisure-time physical activity, and estimated GFR. Both daily and cumulative
      cigarette consumption were associated with an increased risk for glomerular
      hyperfiltration and proteinuria in a dose-response manner. CONCLUSIONS: In middle
      aged Japanese men, smoking was associated with an increased risk of glomerular
      hyperfiltration and dipstick proteinuria. Of importance, past smokers did not
      exhibit any increased risk for these conditions.

PMID- 21885795
TI  - ASN clinicopathologic conference.

PMID- 21885796
TI  - Ascorbic acid or L-arginine improves cutaneous microvascular function in chronic
      kidney disease.
AB  - We sought to determine whether oxidative stress or a relative deficit of l
      arginine plays a role in reducing cutaneous vasodilation in response to local
      heating in chronic kidney disease (CKD). Eight patients with stage 3-4 CKD and
      eight age- and sex-matched healthy control (HC) subjects were instrumented with
      four microdialysis (MD) fibers for the local delivery of 1) Ringers solution (R),
      2) 20 mM ascorbic acid (AA), 3) 10 mM l-arginine (l-Arg), and 4) 10 mM N(G)-nitro
      l-arginine methyl ester (l-NAME). Red blood cell (RBC) flux was measured via
      laser Doppler flowmetry. A standardized nonpainful local heating protocol (42
      degrees C) was used. Cutaneous vascular conductance (CVC) was calculated as RBC
      flux/MAP and all data were expressed as a percentage of the maximum CVC at each
      site (28 mM sodium nitroprusside, T(loc) = 43 degrees C). The plateau %CVC(max)
      was attenuated in CKD (CKD: 76 +/- 4 vs. HC: 91 +/- 2%CVC(max); P < 0.05) and the
      NO contribution to the plateau was lower in CKD (CKD: 39 +/- 7, HC: 54 +/- 5; P <
      0.05). The plateau %CVC(max) in the CKD group was significantly greater at the AA
      and l-Arg sites compared with R (AA: 89 +/- 2; l-Arg: 90 +/- 1; R: 76 +/- 4; P <
      0.05) and did not differ from HC. Initial peak %CVC(max) was also significantly
      attenuated at the R and l-Arg sites in CKD (P < 0.05) but did not differ at the
      AA site. These results suggest that cutaneous microvascular function is impaired
      in stage 3-4 CKD and that oxidative stress and a deficit of l-arginine play a
      role in this impairment.

PMID- 21885797
TI  - Sensorimotor function of the upper-airway muscles and respiratory sensory
      processing in untreated obstructive sleep apnea.
AB  - Numerous studies have demonstrated upper-airway neuromuscular abnormalities
      during wakefulness in snorers and obstructive sleep apnea (OSA) patients.
      However, the functional role of sensorimotor impairment in OSA
      pathogenesis/disease progression and its potential effects on protective upper
      airway reflexes, measures of respiratory sensory processing, and force
      characteristics remain unclear. This study aimed to gain physiological insight
      into the potential role of sensorimotor impairment in OSA pathogenesis/disease
      progression by comparing sensory processing properties (respiratory-related
      evoked potentials; RREP), functionally important protective reflexes
      (genioglossus and tensor palatini) across a range of negative pressures (brief
      pulses and entrained iron lung ventilation), and tongue force and time to task
      failure characteristics between 12 untreated OSA patients and 13 controls. We
      hypothesized that abnormalities in these measures would be present in OSA
      patients. Upper-airway reflexes (e.g., genioglossus onset latency, 20 +/- 1 vs.
      19 +/- 2 ms, P = 0.82), early RREP components (e.g., P1 latency 25 +/- 2 vs. 25
      +/- 1 ms, P = 0.78), and the slope of epiglottic pressure vs. genioglossus
      activity during iron lung ventilation (-0.68 +/- 1.0 vs. -0.80 +/- 2.0
      cmH(2)O/%max, P = 0.59) were not different between patients and controls. Maximal
      tongue protrusion force was greater in OSA patients vs. controls (35 +/- 2 vs. 27
      +/- 2 N, P < 0.01), but task failure occurred more rapidly (149 +/- 24 vs. 254 +/
      23 s, P < 0.01). Upper-airway protective reflexes across a range of negative
      pressures as measured by electromyography and the early P1 component of the RREP
      are preserved in OSA patients during wakefulness. Consistent with an adaptive
      training effect, tongue protrusion force is increased, not decreased, in
      untreated OSA patients. However, OSA patients may be vulnerable to fatigue of
      upper-airway dilator muscles, which could contribute to disease progression.

PMID- 21885798
TI  - Taking a HIT for the heart: why training intensity matters.

PMID- 21885799
TI  - Temporal pattern of left ventricular structural and functional remodeling
      following reversal of volume overload heart failure.
AB  - Current surgical management of volume overload-induced heart failure (HF) leads
      to variable recovery of left ventricular (LV) function despite a return of LV
      geometry. The mechanisms that prevent restoration of function are unknown but may
      be related to the timing of intervention and the degree of LV contractile
      impairment. This study determined whether reduction of aortocaval fistula (ACF)
      induced LV volume overload during the compensatory stage of HF results in
      beneficial LV structural remodeling and restoration of pump function. Rats were
      subjected to ACF for 4 wk; a subset then received a load-reversal procedure by
      closing the shunt using a custom-made stent graft approach. Echocardiography or
      in vivo pressure-volume analysis was used to assess LV morphology and function in
      sham rats; rats subjected to 4-, 8-, or 15-wk ACF; and rats subjected to 4-wk ACF
      followed by 4- or 11-wk reversal. Structural and functional changes were
      correlated to LV collagen content, extracellular matrix (ECM) proteins, and
      hypertrophic markers. ACF-induced volume overload led to progressive LV chamber
      dilation and contractile dysfunction. Rats subjected to short-term reversal (4-wk
      ACF + 4-wk reversal) exhibited improved chamber dimensions (LV diastolic
      dimension) and LV compliance that were associated with ECM remodeling and
      normalization of atrial and brain natriuretic peptides. Load-independent
      parameters indicated LV systolic (preload recruitable stroke work, Ees) and
      diastolic dysfunction (tau, arterial elastance). These changes were associated
      with an altered alpha/beta-myosin heavy chain ratio. However, these changes were
      normalized to sham levels in long-term reversal rats (4-wk ACF + 11-wk reversal).
      Acute hemodynamic changes following ACF reversal improve LV geometry, but LV
      dysfunction persists. Gradual restoration of function was related to
      normalization of eccentric hypertrophy, LV wall stress, and ECM remodeling. These
      results suggest that mild to moderate LV systolic dysfunction may be an important
      indicator of the ability of the myocardium to remodel following the reversal of
      hemodynamic overload.

PMID- 21885801
TI  - NADPH oxidase: short-term foe, long-term friend.

PMID- 21885802
TI  - Evaluation of artificial neural network algorithms for predicting METs and
      activity type from accelerometer data: validation on an independent sample.
AB  - Previous work from our laboratory provided a "proof of concept" for use of
      artificial neural networks (nnets) to estimate metabolic equivalents (METs) and
      identify activity type from accelerometer data (Staudenmayer J, Pober D, Crouter
      S, Bassett D, Freedson P, J Appl Physiol 107: 1330-1307, 2009). The purpose of
      this study was to develop new nnets based on a larger, more diverse, training
      data set and apply these nnet prediction models to an independent sample to
      evaluate the robustness and flexibility of this machine-learning modeling
      technique. The nnet training data set (University of Massachusetts) included 277
      participants who each completed 11 activities. The independent validation sample
      (n = 65) (University of Tennessee) completed one of three activity routines.
      Criterion measures were 1) measured METs assessed using open-circuit indirect
      calorimetry; and 2) observed activity to identify activity type. The nnet input
      variables included five accelerometer count distribution features and the lag-1
      autocorrelation. The bias and root mean square errors for the nnet MET trained on
      University of Massachusetts and applied to University of Tennessee were +0.32 and
      1.90 METs, respectively. Seventy-seven percent of the activities were correctly
      classified as sedentary/light, moderate, or vigorous intensity. For activity
      type, household and locomotion activities were correctly classified by the nnet
      activity type 98.1 and 89.5% of the time, respectively, and sport was correctly
      classified 23.7% of the time. Use of this machine-learning technique operates
      reasonably well when applied to an independent sample. We propose the creation of
      an open-access activity dictionary, including accelerometer data from a broad
      array of activities, leading to further improvements in prediction accuracy for
      METs, activity intensity, and activity type.

PMID- 21885800
TI  - Local control of skeletal muscle blood flow during exercise: influence of
      available oxygen.
AB  - Reductions in oxygen availability (O(2)) by either reduced arterial O(2) content
      or reduced perfusion pressure can have profound influences on the circulation,
      including vasodilation in skeletal muscle vascular beds. The purpose of this
      review is to put into context the present evidence regarding mechanisms
      responsible for the local control of blood flow during acute systemic hypoxia
      and/or local hypoperfusion in contracting muscle. The combination of submaximal
      exercise and hypoxia produces a "compensatory" vasodilation and augmented blood
      flow in contracting muscles relative to the same level of exercise under normoxic
      conditions. A similar compensatory vasodilation is observed in response to local
      reductions in oxygen availability (i.e., hypoperfusion) during normoxic exercise.
      Available evidence suggests that nitric oxide (NO) contributes to the
      compensatory dilator response under each of these conditions, whereas adenosine
      appears to only play a role during hypoperfusion. During systemic hypoxia the NO
      mediated component of the compensatory vasodilation is regulated through a beta
      adrenergic receptor mechanism at low-intensity exercise, while an additional (not
      yet identified) source of NO is likely to be engaged as exercise intensity
      increases during hypoxia. Potential candidates for stimulating and/or interacting
      with NO at higher exercise intensities include prostaglandins and/or ATP.
      Conversely, prostaglandins do not appear to play a role in the compensatory
      vasodilation during exercise with hypoperfusion. Taken together, the data for
      both hypoxia and hypoperfusion suggest NO is important in the compensatory
      vasodilation seen when oxygen availability is limited. This is important from a
      basic biological perspective and also has pathophysiological implications for
      diseases associated with either hypoxia or hypoperfusion.

PMID- 21885803
TI  - Force control of quadriceps muscle is bilaterally impaired in subacute stroke.
AB  - We tested the hypothesis that force variability and error during maintenance of
      submaximal isometric knee extension are greater in subacute stroke patients than
      in controls and are related to motor impairments. Contralesional (more-affected)
      and ipsilesional (less-affected) legs of 33 stroke patients with sufficiently
      high motor abilities (62 +/- 13 yr, 16 +/- 2 days postinjury) and the dominant
      leg of 20 controls (62 +/- 10 yr) were tested in sitting position. After peak
      knee extension torque [maximum voluntary contraction (MVC)] was established,
      subjects maintained 10, 20, 30, and 50% of MVC as steady and accurate as possible
      for 10 s by matching voluntary force to the target level displayed on a monitor.
      Coefficient of variation (CV) and root-mean-square error (RMSE) were used to
      quantify force variability and error, respectively. The MVC was significantly
      smaller in the more-affected than less-affected leg, and both were significantly
      lower than in controls. The CV was significantly larger in the more-affected than
      less-affected leg at 20 and 50% MVC, whereas both were significantly larger
      compared with controls across all force levels. Both more-affected and less
      affected legs of patients showed significantly greater RMSE than controls at 30
      and 50% MVC. The CV and RMSE were not related to the Fugl-Meyer motor score or to
      the Rivermead Mobility Index. The CV negatively correlated with MVC in controls
      but only in the less-affected leg of patients. It is concluded that isometric
      knee extension strength and force control are bilaterally impaired soon after
      stroke but more so in the more-affected leg. Future studies should examine
      possible mechanisms and the evolution of these changes.

PMID- 21885804
TI  - In ovo administration of rhIGF-1 to duck eggs affects the expression of myogenic
      transcription factors and muscle mass during late embryo development.
AB  - In ovo administration of IGF-1 to poultry eggs has effective roles on post
      hatching muscle development. However, the secondary muscle development stages at
      the late embryo development stage are important for muscle fiber formation and
      differentiation. To investigate the roles of in ovo administration of IGF-1 on
      duck secondary muscle development, we injected rhIGF-1 into duck eggs in hatching
      at day 12. After administration on days 18, 21, 24, and 27 in hatching (E18d,
      E21d, E24d, and E27d, respectively), muscle samples were isolated, and the muscle
      tissue weight, muscle fiber parameters, and myoblast proliferation rate in leg
      and breast muscle were analyzed. Additionally, the expression levels of the
      transcription factors MyoG and MRF4 were detected using qPCR. Results show that
      embryo body weight and muscle fiber parameters, including muscle fiber diameter
      (MFD) and the number of myofibers per unit area, are upregulated in IGF-1-treated
      groups. Moreover, the transcription factors MyoG and MRF4 are expressed at higher
      levels in the experimental groups compared with the control groups. These results
      suggest that in ovo administration of IGF-1 to poultry eggs can mediate the
      expression of MyoG and MRF4, induce myoblast proliferation, and finally influence
      muscle development during the secondary muscle development stages.

PMID- 21885805
TI  - Determinants of time trial performance and maximal incremental exercise in highly
      trained endurance athletes.
AB  - Human endurance performance can be predicted from maximal oxygen consumption
      (Vo(2max)), lactate threshold, and exercise efficiency. These physiological
      parameters, however, are not wholly exclusive from one another, and their
      interplay is complex. Accordingly, we sought to identify more specific
      measurements explaining the range of performance among athletes. Out of 150
      separate variables we identified 10 principal factors responsible for
      hematological, cardiovascular, respiratory, musculoskeletal, and neurological
      variation in 16 highly trained cyclists. These principal factors were then
      correlated with a 26-km time trial and test of maximal incremental power output.
      Average power output during the 26-km time trial was attributed to, in order of
      importance, oxidative phosphorylation capacity of the vastus lateralis muscle (P
      = 0.0005), steady-state submaximal blood lactate concentrations (P = 0.0017), and
      maximal leg oxygenation (sO(2LEG)) (P = 0.0295), accounting for 78% of the
      variation in time trial performance. Variability in maximal power output, on the
      other hand, was attributed to total body hemoglobin mass (Hb(mass); P = 0.0038),
      Vo(2max) (P = 0.0213), and sO(2LEG) (P = 0.0463). In conclusion, 1) skeletal
      muscle oxidative capacity is the primary predictor of time trial performance in
      highly trained cyclists; 2) the strongest predictor for maximal incremental power
      output is Hb(mass); and 3) overall exercise performance (time trial performance +
      maximal incremental power output) correlates most strongly to measures regarding
      the capability for oxygen transport, high Vo(2max) and Hb(mass), in addition to
      measures of oxygen utilization, maximal oxidative phosphorylation, and electron
      transport system capacities in the skeletal muscle.

PMID- 21885806
TI  - New SNM/SNMTS officers.

PMID- 21885807
TI  - Recall of CardioGen-82.

PMID- 21885808
TI  - Updates from the ABNM.

PMID- 21885810
TI  - Guidelines differentiate Alzheimer dementia and disease.

PMID- 21885811
TI  - Planning for the future of nuclear and molecular imaging.

PMID- 21885812
TI  - Chemoprevention of colon and small intestinal tumorigenesis in APC(Min/+) mice by
      licofelone, a novel dual 5-LOX/COX inhibitor: potential implications for human
      colon cancer prevention.
AB  - Preclinical and clinical studies suggest that 5-lipoxygenase (5-LOX), such as COX
      2, is a potential target for colon cancer inhibition and, in part, contributes to
      cardiovascular side effects associated with COX-2 inhibitors. Experiments were
      designed to assess the chemopreventive effects of a novel dual 5-LOX/COX
      inhibitor, licofelone {[6-(4-chlorophenyl)-2,2-dimethyl-7-phenyl-2,3-dihydro-1H
      pyrrolizin-5-yl] acetic acid}, in APC(Min/+) mouse intestinal tumorigenesis. Six
      week-old male and female APC(Min/+) mice (n = 10 per group) were fed with control
      American Institute of Nutrition-76A diet or diets containing 150 or 300 ppm
      licofelone for 14 weeks (~100 days), and intestinal tumors were evaluated for
      tumor multiplicity and size. Licofelone significantly inhibited total intestinal
      tumor multiplicity and size in a dose-dependent manner (P < 0.0001; mean tumors
      for 0, 150, and 300 ppm: 48.8, 17, and 8, respectively, in male mice; and 34.3,
      8.8, and 5.5, respectively, in female mice). Licofelone at high dose showed more
      than 83% (P < 0.0001) tumor inhibition in both genders of mice. One hundred and
      fifty and 300 ppm licofelone resulted in 86% to 97% inhibition of polyps having
      size greater than 2 mm. One hundred and fifty and 300 ppm licofelone caused more
      than 72% and 100% inhibition of colonic tumors, respectively. Importantly, in
      mice fed with licofelone, tumors showed significantly reduced proliferating cell
      nuclear antigen expression (70%, P < 0.0001), increased terminal deoxynucleotidyl
      transferase-mediated dUTP nick end labeling-positive cells (75%, P < 0.0001), and
      there was dose-dependent suppression of serum triglycerides (71%-83%, P <
      0.0001), decreased inflammatory cytokines; and decreased COX and 5-LOX activities
      (57%-64%, P < 0.0001). Also, compared with 300 ppm celecoxib, 300 ppm licofelone
      provided better efficacy in suppressing tumor growth. These observations show
      that a novel dual 5-LOX/COX inhibitor dramatically suppresses small intestinal
      and colonic tumor formation in APC(Min/+) mice.

PMID- 21885813
TI  - (3-Chloroacetyl)-indole, a novel allosteric AKT inhibitor, suppresses colon
      cancer growth in vitro and in vivo.
AB  - Indole-3-carbinol (I3C) is produced in Brassica vegetables such as broccoli and
      cabbage and has been shown to inhibit proliferation and induce apoptosis in
      various cancer cells, including breast, prostate, colon, and leukemia. However,
      only high doses of I3C were shown to inhibit cell proliferation (IC(50) = 200-300
      MUmol/L). Our goal here was to develop a more potent antitumor agent by modifying
      the structure of I3C. We created I3C derivatives and found that (3-chloroacetyl)
      indole (3CAI) more strongly inhibited colon cancer cell growth than I3C. In
      addition, by screening 85 kinases in a competitive kinase assay, we found that
      3CAI was a specific AKT inhibitor. AKT is a serine/threonine kinase that plays a
      pivotal role in promoting transformation and chemoresistance by inducing
      proliferation and inhibiting apoptosis. Therefore, AKT is regarded as a critical
      target for cancer therapy. 3ICA, a derivative of I3C, is a potent and specific
      AKT inhibitor. This compound showed significant inhibition of AKT in an in vitro
      kinase assay and suppressed expression of AKT direct downstream targets such as
      mTOR and GSK3beta as well as induced growth inhibition and apoptosis in colon
      cancer cells. In addition, oral administration of this potent AKT inhibitor
      suppressed cancer cell growth in an in vivo xenograft mouse model.

PMID- 21885815
TI  - Inhibition by resistant starch of red meat-induced promutagenic adducts in mouse
      colon.
AB  - Population studies have shown that high red meat intake may increase colorectal
      cancer risk. Our aim was to examine the effect of different amounts and sources
      of dietary protein on induction of the promutagenic adduct O(6)-methyl-2
      deoxyguanosine (O(6)MeG) in colonocytes, to relate these to markers of large
      bowel protein fermentation and ascertain whether increasing colonic carbohydrate
      fermentation modified these effects. Mice (n = 72) were fed 15% or 30% protein as
      casein or red meat or 30% protein with 10% high amylose maize starch as the
      source of resistant starch. Genetic damage in distal colonocytes was detected by
      immunohistochemical staining for O(6)MeG and apoptosis. Feces were collected for
      measurement of pH, ammonia, phenols, p-cresol, and short-chain fatty acids
      (SCFA). O(6)MeG and fecal p-cresol concentrations were significantly higher with
      red meat than with casein (P < 0.018), with adducts accumulating in cells at the
      crypt apex. DNA adducts (P < 0.01) and apoptosis (P < 0.001) were lower and
      protein fermentation products (fecal ammonia, P < 0.05; phenol, P < 0.0001)
      higher in mice fed resistant starch. Fecal SCFA levels were also higher in mice
      fed resistant starch (P < 0.0001). This is the first demonstration that high
      protein diets increase promutagenic adducts (O(6)MeG) in the colon and dietary
      protein type seems to be the critical factor. The delivery of fermentable
      carbohydrate to the colon (as resistant starch) seems to switch from fermentation
      of protein to that of carbohydrate and a reduction in adduct formation,
      supporting previous observations that dietary resistant starch opposes the
      mutagenic effects of dietary red meat.

PMID- 21885814
TI  - Nonsteroidal anti-inflammatory drugs and glioma in the NIH-AARP Diet and Health
      Study cohort.
AB  - Several case-control studies have suggested that nonsteroidal anti-inflammatory
      drugs (NSAIDs) reduce risk for glioblastoma, an aggressive form of brain cancer.
      Prospective investigations have not observed such an association, but these
      studies lacked adequate brain cancer case numbers and did not stratify by
      histologic subtype. We prospectively investigated the association between NSAID
      use and risk of all glioma as well as the risk of glioblastoma subtype in the
      National Institutes of Health (NIH)-AARP Diet and Health Study. The frequency of
      aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using a
      self-administered questionnaire. Hazard ratios (HRs) and 95% confidence intervals
      (CI) were estimated using Cox regression models with age as the underlying time
      metric, adjusted for sex, race, and history of heart disease. The analysis
      included 302,767 individuals, with 341 incident glioma cases (264 glioblastoma).
      No association was observed between regular use (>2 times/wk) of aspirin and risk
      of glioma (HR = 1.16; 95% CI, 0.87-1.56) or glioblastoma (HR = 1.17; 95% CI, 0.83
      1.64) as compared with no use. Null associations were also observed for
      nonaspirin NSAID use (HR for glioma = 0.90; 95% CI, 0.65-1.25 and HR for
      glioblastoma = 0.83; 95% CI, 0.56-1.20) as compared with no use. Our findings
      from this large prospective study do not support an inverse association between
      NSAIDs and risk of all glioma or glioblastoma.

PMID- 21885817
TI  - Life sciences career exploration.

PMID- 21885816
TI  - Changes in breast density and circulating estrogens in postmenopausal women
      receiving adjuvant anastrozole.
AB  - Factors associated with an increased risk of breast cancer include prior breast
      cancer, high circulating estrogens, and increased breast density. Adjuvant
      aromatase inhibitors are associated with a reduction in incidence of
      contralateral breast cancer. We conducted a prospective, single-arm, single
      institution study to determine whether use of anastrozole is associated with
      changes in contralateral breast density and circulating estrogens. Eligible
      patients included postmenopausal women with hormone receptor-positive early-stage
      breast cancer who had completed local therapy, had an intact contralateral
      breast, and were recommended an aromatase inhibitor as their only systemic
      therapy. Participants received anastrozole 1 mg daily for 12 months on study. We
      assessed contralateral breast density and serum estrogens at baseline, 6, and 12
      months. The primary endpoint was change in contralateral percent breast density
      from baseline to 12 months. Secondary endpoints included change in serum estrone
      sulfate from baseline to 12 months. Fifty-four patients were accrued. At 12
      months, compared with baseline, there was a nonstatistically significant
      reduction in breast density (mean change: -16%, 95% CI: -30 to 2, P = 0.08) and a
      significant reduction in estrone sulfate (mean change: -93%, 95% CI: -94 to -91,
      P < 0.001). Eighteen women achieved 20% or greater relative reduction in
      contralateral percent density at 12 months compared with baseline; however, no
      measured patient or disease characteristics distinguished these women from the
      overall population. Large trials are required to provide additional data on the
      relationship between aromatase inhibitors and breast density and, more
      importantly, whether observed changes in breast density correlate with meaningful
      disease-specific outcomes.

PMID- 21885819
TI  - A life in science.

PMID- 21885820
TI  - Improving graduate education to support a branching career pipeline:
      recommendations based on a survey of doctoral students in the basic biomedical
      sciences.
AB  - Today's doctoral programs continue to prepare students for a traditional academic
      career path despite the inadequate supply of research-focused faculty positions.
      We advocate for a broader doctoral curriculum that prepares trainees for a wide
      range of science-related career paths. In support of this argument, we describe
      data from our survey of doctoral students in the basic biomedical sciences at
      University of California, San Francisco (UCSF). Midway through graduate training,
      UCSF students are already considering a broad range of career options, with one
      third intending to pursue a non-research career path. To better support this
      branching career pipeline, we recommend that national standards for training and
      mentoring include emphasis on career planning and professional skills development
      to ensure the success of PhD-level scientists as they contribute to a broadly
      defined global scientific enterprise.

PMID- 21885821
TI  - Mentoring interdisciplinary undergraduate students via a team effort.
AB  - We describe how a team approach that we developed as a mentoring strategy can be
      used to recruit, advance, and guide students to be more interested in the
      interdisciplinary field of mathematical biology, and lead to success in
      undergraduate research in this field. Students are introduced to research in
      their first semester via lab rotations. Their participation in the research of
      four faculty members-two from biology and two from mathematics-gives them a first
      hand overview of research in quantitative biology and also some initial
      experience in research itself. However, one of the primary goals of the lab
      rotation experience is that of developing teams of students and faculty that
      combine mathematics and statistics with biology and the life sciences, teams that
      subsequently mentor undergraduate research in genuine interdisciplinary
      environments. Thus, the team concept serves not only as a means of establishing
      interdisciplinary research, but also as a means of incorporating new students
      into existing research efforts that will then track those students into
      meaningful research of their own. We report how the team concept is used to
      support undergraduate research in mathematical biology and what types of team
      building strategies have worked for us.

PMID- 21885822
TI  - Teaching biology through statistics: application of statistical methods in
      genetics and zoology courses.
AB  - Incorporation of mathematics into biology curricula is critical to underscore for
      undergraduate students the relevance of mathematics to most fields of biology and
      the usefulness of developing quantitative process skills demanded in modern
      biology. At our institution, we have made significant changes to better integrate
      mathematics into the undergraduate biology curriculum. The curricular revision
      included changes in the suggested course sequence, addition of statistics and
      precalculus as prerequisites to core science courses, and incorporating
      interdisciplinary (math-biology) learning activities in genetics and zoology
      courses. In this article, we describe the activities developed for these two
      courses and the assessment tools used to measure the learning that took place
      with respect to biology and statistics. We distinguished the effectiveness of
      these learning opportunities in helping students improve their understanding of
      the math and statistical concepts addressed and, more importantly, their ability
      to apply them to solve a biological problem. We also identified areas that need
      emphasis in both biology and mathematics courses. In light of our observations,
      we recommend best practices that biology and mathematics academic departments can
      implement to train undergraduates for the demands of modern biology.

PMID- 21885823
TI  - The Colorado Learning Attitudes about Science Survey (CLASS) for use in Biology.
AB  - This paper describes a newly adapted instrument for measuring novice-to-expert
      like perceptions about biology: the Colorado Learning Attitudes about Science
      Survey for Biology (CLASS-Bio). Consisting of 31 Likert-scale statements, CLASS
      Bio probes a range of perceptions that vary between experts and novices,
      including enjoyment of the discipline, propensity to make connections to the real
      world, recognition of conceptual connections underlying knowledge, and problem
      solving strategies. CLASS-Bio has been tested for response validity with both
      undergraduate students and experts (biology PhDs), allowing student responses to
      be directly compared with a consensus expert response. Use of CLASS-Bio to date
      suggests that introductory biology courses have the same challenges as
      introductory physics and chemistry courses: namely, students shift toward more
      novice-like perceptions following instruction. However, students in upper
      division biology courses do not show the same novice-like shifts. CLASS-Bio can
      also be paired with other assessments to: 1) examine how student perceptions
      impact learning and conceptual understanding of biology, and 2) assess and
      evaluate how pedagogical techniques help students develop both expertise in
      problem solving and an expert-like appreciation of the nature of biology.

PMID- 21885824
TI  - Classroom-based science research at the introductory level: changes in career
      choices and attitude.
AB  - Our study, focused on classroom-based research at the introductory level and
      using the Phage Genomics course as the model, shows evidence that first-year
      students doing research learn the process of science as well as how scientists
      practice science. A preliminary but notable outcome of our work, which is based
      on a small sample, is the change in student interest in considering different
      career choices such as graduate education and science in general. This is
      particularly notable, as previous research has described research internships as
      clarifying or confirming rather than changing undergraduates' decisions to pursue
      graduate education. We hypothesize that our results differ from previous studies
      of the impact of engaging in research because the students in our study are still
      in the early stages of their undergraduate careers. Our work builds upon the
      classroom-based research movement and should be viewed as encouraging to the
      Vision and Change in Undergraduate Biology Education movement advocated by the
      American Association for the Advancement of Science, the National Science
      Foundation, and other undergraduate education stakeholders.

PMID- 21885825
TI  - Culturally relevant inquiry-based laboratory module implementations in upper
      division genetics and cell biology teaching laboratories.
AB  - Today, more minority students are entering undergraduate programs than ever
      before, but they earn only 6% of all science or engineering PhDs awarded in the
      United States. Many studies suggest that hands-on research activities enhance
      students' interest in pursuing a research career. In this paper, we present a
      model for the implementation of laboratory research in the undergraduate teaching
      laboratory using a culturally relevant approach to engage students. Laboratory
      modules were implemented in upper-division genetics and cell biology courses
      using cassava as the central theme. Students were asked to bring cassava samples
      from their respective towns, which allowed them to compare their field-collected
      samples against known lineages from agricultural stations at the end of the
      implementation. Assessment of content and learning perceptions revealed that our
      novel approach allowed students to learn while engaged in characterizing Puerto
      Rican cassava. In two semesters, based on the percentage of students who answered
      correctly in the premodule assessment for content knowledge, there was an overall
      improvement of 66% and 55% at the end in the genetics course and 24% and 15% in
      the cell biology course. Our proposed pedagogical model enhances students'
      professional competitiveness by providing students with valuable research skills
      as they work on a problem to which they can relate.

PMID- 21885826
TI  - Online teaching tool simplifies faculty use of multimedia and improves student
      interest and knowledge in science.
AB  - Digital technologies can improve student interest and knowledge in science.
      However, researching the vast number of websites devoted to science education and
      integrating them into undergraduate curricula is time-consuming. We developed an
      Adobe ColdFusion- and Adobe Flash-based system for simplifying the construction,
      use, and delivery of electronic educational materials in science. The Online
      Multimedia Teaching Tool (OMTT) in Neuroscience was constructed from a ColdFusion
      based online interface, which reduced the need for programming skills and the
      time for curriculum development. The OMTT in Neuroscience was used by faculty to
      enhance their lectures in existing curricula. Students had unlimited online
      access to encourage user-centered exploration. We found the OMTT was rapidly
      adapted by multiple professors, and its use by undergraduate students was
      consistent with the interpretation that the OMTT improved performance on exams
      and increased interest in the field of neuroscience.

PMID- 21885827
TI  - Are comic books an effective way to engage nonmajors in learning and appreciating
      science?
AB  - Comic books employ a complex interplay of text and images that gives them the
      potential to effectively convey concepts and motivate student engagement. This
      makes comics an appealing option for educators trying to improve science literacy
      about pressing societal issues involving science and technology. Here, we report
      results from the first systematic assessment of how a science comic book can
      affect student learning and attitudes about biology. We used pre- and
      postinstruction instruments to measure students' attitudes about biology,
      attitudes about comics, and content knowledge about evolution before and after
      using the science comic book Optical Allusions in their classes. On the
      preinstruction instrument, nonmajors reported the lowest scores on the content
      test and attitude surveys relative to the other groups. However, on the
      postinstruction instrument, nonmajors' content scores and attitudes showed a
      statistically significant improvement after using the comic book, particularly
      among those with lower content knowledge at the start of the semester. The
      improvement in attitudes about biology was correlated to attitudes about comics,
      suggesting that the comic may have played a role in engaging and shaping student
      attitudes in a positive way.

PMID- 21885828
TI  - A comprehensive analysis of high school genetics standards: are states keeping
      pace with modern genetics?
AB  - Science education in the United States will increasingly be driven by testing and
      accountability requirements, such as those mandated by the No Child Left Behind
      Act, which rely heavily on learning outcomes, or "standards," that are currently
      developed on a state-by-state basis. Those standards, in turn, drive curriculum
      and instruction. Given the importance of standards to teaching and learning, we
      investigated the quality of life sciences/biology standards with respect to
      genetics for all 50 states and the District of Columbia, using core concepts
      developed by the American Society of Human Genetics as normative benchmarks. Our
      results indicate that the states' genetics standards, in general, are poor, with
      more than 85% of the states receiving overall scores of Inadequate. In
      particular, the standards in virtually every state have failed to keep pace with
      changes in the discipline as it has become genomic in scope, omitting concepts
      related to genetic complexity, the importance of environment to phenotypic
      variation, differential gene expression, and the differences between inherited
      and somatic genetic disease. Clearer, more comprehensive genetics standards are
      likely to benefit genetics instruction and learning, help prepare future genetics
      researchers, and contribute to the genetic literacy of the U.S. citizenry.

PMID- 21885829
TI  - Early atheroma-derived agonists of peroxisome proliferator-activated receptor
      gamma trigger intramedial angiogenesis in a smooth muscle cell-dependent manner.
AB  - RATIONALE: Neovascularization favors intraplaque hemorrhage and plaque rupture.
      Development of therapeutic strategies against atheromatous angiogenesis requires
      elucidation of its initiating factors. OBJECTIVE: We investigated the
      contribution of smooth muscle cells (SMCs) and atheroma-derived lipids to the
      initiation of atheroma-associated neoangiogenesis. METHODS AND RESULTS: Forty
      human aortic segments, each harvested from a different donor, were classified as
      healthy or as bearing early atheromatous lesions, including fatty streaks and
      fibrolipidic atheroma, according to their histological features. Immunostaining
      for blood vessels and vascular endothelial growth factor-A (VEGF-A), as well as
      measurement of VEGF-A protein and mRNA levels by ELISA and real-time PCR,
      revealed that angiogenesis and VEGF-A production were enhanced in the medial
      layer of atheromatous aortas. The intramedial vessel density and invasiveness and
      the production of VEGF-A by medial SMCs were indeed increased in atheromatous
      aortas compared with healthy aortas. Furthermore, intimal layers of atheromatous
      aortas were enriched in soluble lipid mediators capable of inducing a sustained
      increase in VEGF-A production by medial SMCs, turning these cells into potent
      inducers of angiogenesis when incorporated into mouse Matrigel implants. Both
      effects were inhibited by the peroxisome proliferator-activated receptor-gamma
      inhibitor GW9662 and mimicked by its agonist, rosiglitazone. CONCLUSIONS: We show
      that VEGF-A production is upregulated in medial SMCs of human atheromatous aortas
      and that peroxisome proliferator-activated receptor-gamma agonists derived from
      early intimal lesions are likely to contribute to this phenotypic change. Our
      findings suggest that medial SMCs are central organizers of an angiogenic
      response initiated by the subendothelial accumulation of atherogenic lipids.

PMID- 21885831
TI  - Autologous mesenchymal stem cells mobilize cKit+ and CD133+ bone marrow
      progenitor cells and improve regional function in hibernating myocardium.
AB  - RATIONALE: Mesenchymal stem cells (MSCs) improve function after infarction, but
      their mechanism of action remains unclear, and the importance of reduced scar
      volume, cardiomyocyte proliferation, and perfusion is uncertain. OBJECTIVE: The
      present study was conducted to test the hypothesis that MSCs mobilize bone marrow
      progenitor cells and improve function by stimulating myocyte proliferation in
      collateral-dependent hibe rnating myocardium. METHODS AND RESULTS: Swine with
      chronic hibernating myocardium received autologous intracoronary MSCs (icMSCs;
      ~44 *10(6) cells, n = 10) 4 months after instrumentation and were studied up to 6
      weeks later. Physiological and immunohistochemical findings were compared with
      untreated hibernating animals (n = 7), sham-normal animals (n = 5), and icMSC
      treated sham-normal animals (n = 6). In hibernating myocardium, icMSCs increased
      function (percent wall thickening of the left anterior descending coronary artery
      24 +/- 4% to 43 +/- 5%, P < 0.05), although left anterior descending coronary
      artery flow reserve (adenosine/rest) remained critically impaired (1.2 +/- 0.1
      versus 1.2 +/- 0.1). Circulating cKit+ and CD133+ bone marrow progenitor cells
      increased transiently after icMSC administration, with a corresponding increase
      in myocardial cKit+/CD133+ and cKit+/CD133- bone marrow progenitor cells (total
      cKit+ from 223 +/- 49 to 4415 +/- 866/10(6) cardiomyocytes, P < 0.05). In
      hibernating hearts, icMSCs increased Ki67+ cardiomyocytes (from 410 +/- 83 to
      2460 +/- 610/10(6) nuclei, P < 0.05) and phospho-histone H3-positive
      cardiomyocytes (from 9 +/- 5 to 116 +/- 12/10(6) nuclei, P < 0.05). Myocyte
      nuclear number (from 75 336 +/- 5037 to 114 424 +/- 9564 nuclei/mm3, P < 0.01)
      and left ventricular mass (from 2.5 +/- 0.1 to 2.8 +/- 0.1 g/kg, P < 0.05)
      increased, yet myocytes were smaller (14.5 +/- 0.4 versus 16.5 +/- 0.4 MUm, P <
      0.05), which supports endogenous cardiomyocyte proliferation. In sham-normal
      animals, icMSCs increased myocardial bone marrow progenitor cells with no effect
      on myocyte proliferation or regional function. CONCLUSIONS: Our results indicate
      that icMSCs improve function in hibernating myocardium independent of coronary
      flow or reduced scar volume. This arises from stimulation of myocyte
      proliferation with increases in cKit+/CD133+ bone marrow progenitor cells and
      cKit+/CD133- resident stem cells, which increase myocyte number and reduce
      cellular hypertrophy.

PMID- 21885832
TI  - A new standard in the conflict of interest policy of the American Heart
      Association.

PMID- 21885833
TI  - beta-MyHC and cardiac hypertrophy: size does matter.

PMID- 21885830
TI  - p63RhoGEF couples Galpha(q/11)-mediated signaling to Ca2+ sensitization of
      vascular smooth muscle contractility.
AB  - RATIONALE: In normal and diseased vascular smooth muscle (SM), the RhoA pathway,
      which is activated by multiple agonists through G protein-coupled receptors
      (GPCRs), plays a central role in regulating basal tone and peripheral resistance.
      This occurs through inhibition of myosin light chain phosphatase, leading to
      increased phosphorylation of the myosin regulatory light chain. Although it is
      thought that specific agonists and GPCRs may couple to distinct RhoA guanine
      nucleotide exchange factors (GEFs), thus raising the possibility of selective
      targeting of specific GEFs for therapeutic use, this notion is largely unexplored
      for SM contraction. OBJECTIVE: We examine whether p63RhoGEF, known to couple
      specifically to Galpha(q/11) in vitro, is functional in blood vessels as a
      mediator of RhoA activation and if it is selectively activated by Galpha(q/11)
      coupled agonists. METHODS AND RESULTS: We find that p63RhoGEF is present across
      SM tissues and demonstrate that silencing of the endogenous p63RhoGEF in mouse
      portal vein inhibits contractile force induced by endothelin-1 to a greater
      extent than the predominantly Galpha(12/13)-mediated thromboxane analog U46619.
      This is because endothelin-1 acts on Galpha(q/11) as well as Galpha(12/13).
      Introduction of the exogenous isolated pleckstrin-homology (PH) domain of
      p63RhoGEF (residues 331-580) into permeabilized rabbit portal vein inhibited Ca2+
      sensitized force and activation of RhoA, when phenylephrine was used as an
      agonist. This reinforces the results based on endothelin-1, because phenylephrine
      is thought to act exclusively through Galpha(q/11). CONCLUSION: We demonstrate
      that p63RhoGEF selectively couples Galpha(q/11) but not Galpha(12/13), to RhoA
      activation in blood vessels and cultured cells and thus mediates the
      physiologically important Ca2+ sensitization of force induced with Galpha(q/11)
      coupled agonists. Our results suggest that signaling through p63RhoGEF provides a
      novel mechanism for selective regulation of blood pressure.

PMID- 21885834
TI  - Micro-managing myocyte mitosis.

PMID- 21885835
TI  - Not too large and not too small--just the right size: a hippo-sized heart.

PMID- 21885836
TI  - Estrogen signaling and cardiovascular disease.
AB  - Estrogen has pleiotropic effects on the cardiovascular system. The mechanisms by
      which estrogen confers these pleiotropic effects are undergoing active
      investigation. Until a decade ago, all estrogen signaling was thought to occur by
      estrogen binding to nuclear estrogen receptors (estrogen receptor-alpha and
      estrogen receptor-beta), which bind to DNA and function as ligand-activated
      transcription factors. Estrogen binding to the receptor alters gene expression,
      thereby altering cell function. Estrogen also binds to nuclear estrogen receptors
      that are tethered to the plasma membrane, resulting in acute activation of
      signaling kinases such as PI3K. An orphan G-protein-coupled receptor, G-protein
      coupled receptor 30, can also bind estrogen and activate acute signaling
      pathways. Thus, estrogen can alter cell function by binding to different estrogen
      receptors. This article reviews the different estrogen receptors and their
      signaling mechanisms, discusses mechanisms that regulate estrogen receptor levels
      and locations, and considers the cardiovascular effects of estrogen signaling.

PMID- 21885838
TI  - Mechanism of antiarrhythmic effects of flecainide in catecholaminergic
      polymorphic ventricular tachycardia.

PMID- 21885839
TI  - Recent patterns of sex-specific midlife stroke hospitalization rates in the
      United States.
AB  - BACKGROUND AND PURPOSE: Little is known about sex-specific stroke hospitalization
      rates among middle-aged individuals. This study assessed recent temporal trends
      in stroke hospitalizations among persons aged 35 to 64 years in the United
      States. METHODS: The Nationwide Inpatient Sample was used to identify individuals
      with a primary or secondary discharge diagnosis of stroke between 1997 and 2006
      (n=3,161,752). Age-adjusted sex-specific rates of ischemic and hemorrhagic stroke
      hospitalizations were assessed among individuals aged 35 to 64 years. RESULTS:
      Over the study period, stroke hospitalization rates per 100 000 decreased by 10%
      from 66.7 to 60.3 (trend P<0.01) in men and 8% from 52.7 to 48.3 (trend P<0.001)
      in women. The 55- to 64-year age group drove reductions in hospitalization rates:
      slope (rate of change per year)=-12.3 for men and -8.9 for women (both P<0.001).
      Rates increased slightly in men and women aged 35 to 44 years and remained stable
      for persons aged 45 to 54 years. Stroke subtype analysis revealed that rates of
      ischemic stroke hospitalization increased and hemorrhagic stroke hospitalization
      remained stable among individuals aged 35 to 44 years. Rates of ischemic and
      hemorrhagic stroke hospitalizations remained stable among those aged 45 to 54
      years and decreased among persons aged 55 to 64 years. CONCLUSIONS: From 1997 to
      2006, ischemic and hemorrhagic stroke hospitalization rates declined among
      individuals aged 55 to 64 years and remained stable among persons aged 45 to 54
      years; ischemic stroke hospitalization rates increased among individuals aged 35
      to 44 years. Further studies are needed to assess and address increases in
      ischemic stroke hospitalizations among younger individuals.

PMID- 21885837
TI  - Arterial calcification in chronic kidney disease: key roles for calcium and
      phosphate.
AB  - Vascular calcification contributes to the high risk of cardiovascular mortality
      in chronic kidney disease (CKD) patients. Dysregulation of calcium (Ca) and
      phosphate (P) metabolism is common in CKD patients and drives vascular
      calcification. In this article, we review the physiological regulatory mechanisms
      for Ca and P homeostasis and the basis for their dysregulation in CKD. In
      addition, we highlight recent findings indicating that elevated Ca and P have
      direct effects on vascular smooth muscle cells (VSMCs) that promote vascular
      calcification, including stimulation of osteogenic/chondrogenic differentiation,
      vesicle release, apoptosis, loss of inhibitors, and extracellular matrix
      degradation. These studies suggest a major role for elevated P in promoting
      osteogenic/chondrogenic differentiation of VSMC, whereas elevated Ca has a
      predominant role in promoting VSMC apoptosis and vesicle release. Furthermore,
      the effects of elevated Ca and P are synergistic, providing a major stimulus for
      vascular calcification in CKD. Unraveling the complex regulatory pathways that
      mediate the effects of both Ca and P on VSMCs will ultimately provide novel
      targets and therapies to limit the destructive effects of vascular calcification
      in CKD patients.

PMID- 21885840
TI  - Common carotid artery intima-media thickness progression as a predictor of stroke
      in multi-ethnic study of atherosclerosis.
AB  - BACKGROUND AND PURPOSE: Carotid artery intima-media thickness (IMT) is a marker
      of cardiovascular disease associated with incident stroke. We studied whether IMT
      rate of change is associated with stroke. METHODS: We studied 5028 participants
      of the Multi-Ethnic Study of Atherosclerosis (MESA) comprising white, Chinese,
      Hispanic, and black participants free of cardiovascular disease. In this MESA IMT
      progression study, IMT rate of change (mm/year) was the difference in right
      common carotid artery far wall IMT (mm) divided by the interval between 2
      ultrasound examinations (median interval, 32 months). Common carotid artery IMT
      was measured in a region free of plaque. Cardiovascular risk factors and baseline
      IMT were determined when IMT rate of change was measured. Multivariable Cox
      proportional hazards models generated hazard risk ratios (HR) with cardiovascular
      risk factors, ethnicity, and education level/income as predictors. RESULTS: There
      were 42 first-time strokes seen during a mean follow-up of 3.22 years (median,
      3.0 years). Average age was 64.2 years, with 48% males. In multivariable models,
      age (HR, 1.05 per year), systolic blood pressure (HR, 1.02 per mm Hg), lower high
      density lipoprotein cholesterol levels (HR, 0.96 per mg/dL), and IMT rate of
      change (HR, 1.23 per 0.05 mm/year; 95% confidence limit, 1.02-1.48) were
      significantly associated with incident stroke. The upper quartile of IMT rate of
      change had HR of 2.18 (95% confidence limit, 1.07-4.46) compared to the lower 3
      quartiles combined. CONCLUSIONS: Common carotid artery IMT progression is
      associated with incident stroke in this cohort free of prevalent cardiovascular
      disease and atrial fibrillation at baseline.

PMID- 21885841
TI  - Improving door-to-needle times in acute ischemic stroke: the design and rationale
      for the American Heart Association/American Stroke Association's Target: Stroke
      initiative.
AB  - BACKGROUND AND PURPOSE: The benefits of intravenous tissue-type plasminogen
      activator (tPA) in acute ischemic stroke are time-dependent, and guidelines
      recommend a door-to-needle time of <=60 minutes. However, fewer than one third of
      acute ischemic stroke patients who receive tPA are treated within guideline
      recommended door-to-needle times. This article describes the design and rationale
      of TARGET: Stroke, a national initiative organized by the American Heart
      Association/American Stroke Association in partnership with other organizations
      to assist hospitals in increasing the proportion of tPA-treated patients who
      achieve guideline-recommended door-to-needle times. METHODS: The initial program
      goal is to achieve a door-to-needle time<=60 minutes for at least 50% of acute
      ischemic stroke patients. Key best practice strategies previously associated with
      achieving faster door-to-needle times in acute ischemic stroke were identified.
      RESULTS: The 10 key strategies chosen by TARGET: Stroke include emergency medical
      service prenotification, activating the stroke team with a single call, rapid
      acquisition and interpretation of brain imaging, use of specific protocols and
      tools, premixing tPA, a team-based approach, and rapid data feedback. The program
      includes many approaches intended to promote hospital participation, implement
      effective strategies, share best practices, foster collaboration, and achieve
      stated goals. A detailed program evaluation is also included. In the first year,
      TARGET: Stroke has enrolled over 1200 United States hospitals. CONCLUSIONS: 
      TARGET: Stroke, a multidimensional initiative to improve the timeliness of tPA
      administration, aims to elevate clinical performance in the care of acute
      ischemic stroke, facilitate the more rapid integration of evidence into clinical
      practice, and improve outcomes.

PMID- 21885842
TI  - Letter by Sposato and Saposnik regarding article, "Incidence of stroke and
      socioeconomic neighborhood characteristics: an ecological analysis of Dijon
      Stroke Registry".

PMID- 21885843
TI  - Telestroke-guided intravenous tissue-type plasminogen activator treatment
      achieves a similar clinical outcome as thrombolysis at a comprehensive stroke
      center.
AB  - BACKGROUND AND PURPOSE: Telestroke networks offer an opportunity to increase
      tissue-type plasminogen activator use in community hospitals. METHODS: We
      compared 83 patients treated with intravenous tissue-type plasminogen activator
      by telestroke to 59 patients treated after in-person evaluation by the same
      neurologists at a tertiary care stroke center. Onset and door-to-treatment times
      and functional outcome at 90 days were obtained prospectively. Favorable outcome
      was defined as modified Rankin Scale score <=2. RESULTS: Favorable outcome rates
      were comparable between the groups (42.1% versus 37.5%, P=0.7). There was no
      significant difference in the rate of symptomatic hemorrhage. CONCLUSIONS:
      Telestroke is a viable alternative to in-person evaluation when stroke expertise
      is not readily available.

PMID- 21885844
TI  - Cerebrovascular disease pathology and parkinsonian signs in old age.
AB  - BACKGROUND AND PURPOSE: Mild motor symptoms including parkinsonian signs are
      common in old age, but their underlying neuropathology is unclear. We tested the
      hypothesis that cerebrovascular pathologies are related to parkinsonian signs.
      METHODS: We studied brain autopsies from 418 deceased participants from the
      Religious Order Study, who underwent evaluation of parkinsonian signs with a
      modified version of the motor section of the Unified Parkinson's Disease Rating
      Scale. Brains were evaluated for macroscopic and microinfarcts and the severity
      of arteriolosclerosis. Regression analyses were used to examine the association
      of cerebrovascular pathologies with parkinsonian signs. RESULTS: More than 35% of
      cases (N=149) showed macroscopic infarcts. Almost 30% of cases without
      macroscopic infarcts showed pathologies not detected by conventional brain
      imaging: microinfarcts (N=33 [7.9%]), arteriolosclerosis (N=62 [14.8%]), or both
      (N=24 [5.7%]). Macroscopic infarcts, specifically multiple cortical and >=1
      subcortical macroscopic infarcts, were related to higher global parkinsonian
      scores. The presence of multiple and cortical microinfarcts was associated with
      global parkinsonian score. Arteriolosclerosis was associated with global
      parkinsonian score, but this effect was attenuated and no longer significant
      after accounting for infarcts. Each of the 3 pathologies was separately
      associated with parkinsonian gait (macroscopic infarcts [estimate, 0.552; SE,
      0.210; P=0.009]; microinfarcts [estimate, 0.424; SE, 0.213; P=0.047];
      arteriolosclerosis [estimate, 0.191; SE, 0.056; P<0.001]). Further analyses
      showed that subcortical macroscopic and microinfarcts were specifically
      associated with the severity of parkinsonian gait. CONCLUSIONS: Cerebrovascular
      pathologies, including macroscopic infarcts, microinfarcts, and
      arteriolosclerosis, are common in older persons and may be unrecognized common
      etiologies of mild parkinsonian signs, especially parkinsonian gait, in old age.

PMID- 21885845
TI  - Efficiency perspectives on adaptive designs in stroke clinical trials.
AB  - An adaptive design allows the modifications of various features, such as sample
      size and treatment assignments, in a clinical study based on the analysis of
      interim data. The goal is to enhance statistical efficiency by maximizing
      relevant information obtained from the clinical data. The promise of efficiency,
      however, comes with a cost, per se, that is seldom made explicit in the
      literature. This article reviews some commonly used adaptive strategies in early
      phase stroke trials and discusses their associated costs. Specifically, we
      illustrate the trade-offs in several clinical contexts, including dose-finding in
      the Neuroprotection with Statin Therapy for Acute Recovery Trial (NeuSTART),
      futility analyses and internal pilot in Phase 2 proof-of-concept trials, and
      sample size considerations in an imaging-based dose-selection trial. Through
      these illustrations, we demonstrate the potential tension between the
      perspectives of an individual investigator and that of the broader community of
      stakeholders. This understanding is critical to appreciate the limitations, as
      well as the full promise, of adaptive designs, so that investigators can deploy
      an appropriate statistical design--be it adaptive or not--in a clinical study.

PMID- 21885847
TI  - Smooth muscle cell apoptosis promotes vessel remodeling and repair via activation
      of cell migration, proliferation, and collagen synthesis.
AB  - OBJECTIVE: Although vascular smooth muscle cell (VSMC) apoptosis occurs after
      vessel injury and during remodeling, the direct role of VSMC death in determining
      final vessel structure is unclear. We sought to determine the role of VSMC
      apoptosis in vessel remodeling, medial repair, and neointima formation and to
      identify the mediators involved. METHODS AND RESULTS: The left common carotid
      artery was ligated in SM22alpha-human diphtheria toxin receptor mice, in which
      diphtheria toxin treatment selectively induces VSMC apoptosis. Apoptosis induced
      from day 7 to day 14 after ligation significantly increased neointimal and medial
      areas, cell proliferation, migration, and vessel size. Neointima formation
      depended on VSMCs, as VSMC depletion before ligation significantly reduced
      neointimal area and cellularity. In culture, conditioned media from apoptotic
      VSMCs promoted VSMC migration, proliferation, and collagen synthesis. Interleukin
      6 (IL-6) secretion increased 5-fold and IL-1alpha 1.5-fold after apoptosis,
      whereas IL-6 inhibition negated the effect of apoptotic VSMC supernatants on VSMC
      migration, proliferation, and matrix synthesis. CONCLUSION: Signaling from
      apoptotic VSMCs directly promotes vessel remodeling, medial repair, and neointima
      formation after flow reduction. Although lumen size appears to depend on flow,
      VSMC apoptosis is an important determinant of vessel, medial, and neointimal size
      after flow reduction.

PMID- 21885846
TI  - Human thrombomodulin knock-in mice reveal differential effects of human
      thrombomodulin on thrombosis and atherosclerosis.
AB  - OBJECTIVE: We sought to develop a murine model to examine the antithrombotic and
      antiinflammatory functions of human thrombomodulin in vivo. METHODS AND RESULTS:
      Knock-in mice that express human thrombomodulin from the murine thrombomodulin
      gene locus were generated. Compared with wild-type mice, human thrombomodulin
      knock-in mice exhibited decreased protein C activation in the aorta (P<0.01) and
      lung (P<0.001). Activation of endogenous protein C following infusion of thrombin
      was decreased by 90% in knock-in mice compared with wild-type mice (P<0.05).
      Carotid artery thrombosis induced by photochemical injury occurred more rapidly
      in knock-in mice (12+/-3 minutes) than in wild-type mice (31+/-6 minutes;
      P<0.05). No differences in serum cytokine levels were detected between knock-in
      and wild-type mice after injection of endotoxin. When crossed with apolipoprotein
      E-deficient mice and fed a Western diet, knock-in mice had a further decrease in
      protein C activation but did not exhibit increased atherosclerosis. CONCLUSION:
      Expression of human thrombomodulin in place of murine thrombomodulin produces
      viable mice with a prothrombotic phenotype but unaltered responses to systemic
      inflammatory or atherogenic stimuli. This humanized animal model will be useful
      for investigating the function of human thrombomodulin under pathophysiological
      conditions in vivo.

PMID- 21885848
TI  - The cholesterol content of Western diets plays a major role in the paradoxical
      increase in high-density lipoprotein cholesterol and upregulates the macrophage
      reverse cholesterol transport pathway.
AB  - OBJECTIVE: A high-saturated fatty acid- and cholesterol-containing (HFHC) diet is
      considered to be a major risk factor for cardiovascular disease. The present
      study aimed to determine the effects of this Western-type diet on high-density
      lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) from
      macrophages to feces. METHODS AND RESULTS: Experiments were carried out in mice
      fed a low-fat, low-cholesterol diet, an HFHC diet, or an HFHC diet without added
      cholesterol (high-saturated fatty acid and low-cholesterol [HFLC]). The HFHC diet
      caused a significant increase in plasma cholesterol, HDL cholesterol, and liver
      cholesterol and enhanced macrophage-derived [(3)H]cholesterol flux to feces by 3-
      to 4-fold. These effects were greatly reduced in mice fed the HFLC diet. This
      HFHC diet-mediated induction of RCT was sex independent and was not associated
      with obesity or insulin resistance. The HFHC diet caused 1.4- and 3-fold
      increases in [(3)H]cholesterol efflux to plasma and HDL-derived [(3)H]tracer
      fecal excretion, respectively. Unlike a low-fat, low-cholesterol and HFLC diets,
      the HFHC diet increased liver ABCG5/G8 expression. The effect of the HFHC diet on
      fecal macrophage-derived [(3)H]cholesterol excretion was totally blunted in
      ABCG5/G8-deficient mice. CONCLUSION: Despite its deleterious effects on
      atherosclerosis, the HFHC diet promoted a sustained compensatory macrophage-to
      feces RCT. Our data provide direct evidence of the crucial role of dietary
      cholesterol signaling through liver ABCG5/G8 upregulation in the HFHC diet
      mediated induction of macrophage-specific RCT.

PMID- 21885849
TI  - Deficient p27 phosphorylation at serine 10 increases macrophage foam cell
      formation and aggravates atherosclerosis through a proliferation-independent
      mechanism.
AB  - OBJECTIVE: Genetic ablation of the growth suppressor p27(Kip1) (p27) in the mouse
      aggravates atherosclerosis coinciding with enhanced arterial cell proliferation.
      However, it is unknown whether molecular mechanisms that limit p27's protective
      function contribute to atherosclerosis development and whether p27 exerts
      proliferation-independent activities in the arterial wall. This study aims to
      provide insight into both questions by investigating the role in atherosclerosis
      of p27 phosphorylation at serine 10 (p27-phospho-Ser10), a major
      posttranslational modification of this protein. METHODS AND RESULTS:
      Immunoblotting studies revealed a marked reduction in p27-phospho-Ser10 in
      atherosclerotic arteries from apolipoprotein E-null mice, and expression of the
      nonphosphorylatable mutant p27Ser10Ala, either global or restricted to bone
      marrow, accelerated atherosclerosis. p27Ser10Ala expression did not affect cell
      proliferation in early and advanced atheroma but activated RhoA/Rho-associated
      coiled-coil containing protein kinase (ROCK) signaling and promoted macrophage
      foam cell formation in a ROCK-dependent manner. Supporting the clinical relevance
      of these findings, human atherosclerotic coronary arteries exhibited a prominent
      reduction in p27-phospho-Ser10 and increased ezrin/radixin/moesin protein
      phosphorylation, a marker of RhoA/ROCK activation. CONCLUSION: Scarce
      phosphorylation of p27 at Ser10 is a hallmark of human and mouse atherosclerosis
      and promotes disease progression in mice. This proatherogenic effect is mediated
      by a proliferation-independent mechanism that involves augmented foam cell
      formation owing to increased RhoA/ROCK activity. These findings unveil a new
      atheroprotective action of p27 and identify p27-phospho-Ser10 as an attractive
      target for the treatment of atherosclerosis.

PMID- 21885850
TI  - Angiopoietin-1 requires IQ domain GTPase-activating protein 1 to activate Rac1
      and promote endothelial barrier defense.
AB  - OBJECTIVE: IQ domain GTPase-activating protein 1 (IQGAP1) contributes to
      cytoskeletal network regulation in epithelial cells by its scaffolding properties
      and by binding the Rho GTPase Rac1 to maintain its activity. The functions of
      IQGAP1 in endothelial cells beyond angiogenesis remain unclear. We hypothesized
      that IQGAP1 participates in the regulation of endothelial barrier function.
      METHODS AND RESULTS: Silencing IQGAP1 in human microvascular endothelial cells
      resulted in a disruption of adherens junctions, formation of interendothelial
      gaps, and a reduction in barrier function. Furthermore, silencing of IQGAP1
      abrogated the barrier enhancement effect of angiopoietin-1 (Angpt-1) and
      abolished the barrier-stabilizing effect of Angpt-1 on thrombin-stimulated cells.
      Coimmunoprecipitation detected binding of endogenous IQGAP1 with Rac1 at baseline
      that was stronger when Rac1 was activated and weaker when it was deactivated.
      Measurement of GTP-bound Rac1 revealed that Angpt-1 failed to activate Rac1 not
      only if IQGAP1 was silenced but also if cells were transfected with a mutant
      disabled in Rac1 binding (T1050AX2). Furthermore, a dominant-active Rac1 was
      sufficient to completely reverse the morphological and functional changes induced
      by reduction in IQGAP1. CONCLUSION: These experiments are the first demonstration
      of IQGAP1 regulating barrier function in any cell type. Further, our data show
      that Angpt-1 requires IQGAP1 as an indispensable activator of Rac1.

PMID- 21885851
TI  - MicroRNA-16 and microRNA-424 regulate cell-autonomous angiogenic functions in
      endothelial cells via targeting vascular endothelial growth factor receptor-2 and
      fibroblast growth factor receptor-1.
AB  - OBJECTIVE: MicroRNAs play key roles in modulating a variety of cellular processes
      by posttranscriptional regulation of their target genes. Vascular endothelial
      growth factor (VEGF), VEGF receptor-2 (VEGFR2), and fibroblast growth factor
      receptor-1 (FGFR1) were identified by bioinformatic approaches and subsequently
      validated as targets of microRNA (miR)-16 and miR-424 in endothelial cells (ECs).
      METHODS AND RESULTS: Mimetics of these microRNAs reduced VEGF, VEGFR2, and FGFR1
      expression, whereas specific antagonists enhanced their expression. Expression of
      mature miR-16 and miR-424 was upregulated on VEGF or basic fibroblast growth
      factor (bFGF) treatment. This upregulation was accompanied by a parallel increase
      in primary transcript (pri-miR)-16-1 and pri-miR-16-2 but not in pri-miR-424
      levels, indicating a VEGF/bFGF-dependent transcriptional and posttranscriptional
      regulation of miR-16 and miR-424, respectively. Reduced expression of VEGFR2 and
      FGFR1 by miR-16 or miR-424 overexpression regulated VEGF and bFGF signaling
      through these receptors, thereby affecting the activity of downstream components
      of the pathways. Functionally, miR-16 or miR-424 overexpression reduced
      proliferation, migration, and cord formation of ECs in vitro, and lentiviral
      overexpression of miR-16 reduced the ability of ECs to form blood vessels in
      vivo. CONCLUSION: We conclude that these miRNAs fine-tune the expression of
      selected endothelial angiogenic mediators in response to these growth factors.
      Altogether, these findings suggest that miR-16 and miR-424 play important roles
      in regulating cell-intrinsic angiogenic activity of ECs.

PMID- 21885852
TI  - Fatty liver, abdominal visceral fat, and cardiometabolic risk factors: the
      Jackson Heart Study.
AB  - OBJECTIVE: The goal of this study was to examine whether fatty liver and
      abdominal visceral adipose tissue (VAT) are jointly associated with
      cardiometabolic abnormalities. METHODS AND RESULTS: Black participants were from
      the Jackson Heart Study (n=2882, 65% women) who underwent computed tomography.
      Fatty liver was measured by liver attenuation in Hounsfield units (LA), and VAT
      was quantified volumetrically. Cross-sectional associations between LA, VAT, and
      cardiometabolic risk factors were assessed using linear and logistic regression,
      and their joint associations were further examined in 4 subgroups: high-LA/low
      VAT (n=1704), low-LA/low-VAT (n=422), high-LA/high-VAT (n=436), and low-LA/high
      VAT (n=320). Both LA and VAT were associated with most cardiometabolic traits
      (all P<0.0001), which persisted after additional adjustment for each other (LA,
      P<0.01-0.0001; VAT, P<0.0001). In bootstrap analyses, the regression coefficient
      of VAT was significantly greater than LA for triglycerides, high-density
      lipoprotein cholesterol, impaired glucose, and metabolic syndrome (P=0.009
      0.0001). The interaction between LA and VAT was significant for high-density
      lipoprotein cholesterol (P=0.002), impaired glucose (P=0.003), and metabolic
      syndrome (P=0.04). Among 4 subgroups, participants with higher VAT and lower LA
      had higher prevalence of cardiometabolic traits than those with each condition
      alone. CONCLUSION: Both fatty liver and VAT are independent correlates of
      cardiometabolic risk, but the associations are stronger for VAT than for fatty
      liver.

PMID- 21885853
TI  - MicroRNA-758 regulates cholesterol efflux through posttranscriptional repression
      of ATP-binding cassette transporter A1.
AB  - OBJECTIVE: The ATP-binding cassette transporter A1 (ABCA1) is a major regulator
      of macrophage cholesterol efflux and protects cells from excess intracellular
      cholesterol accumulation; however, the mechanism involved in posttranscriptional
      regulation of ABCA1 is poorly understood. We previously showed that microRNA-33
      (miR-33) is 1 regulator. Here, we investigated the potential contribution of
      other microRNAs (miRNAs) to posttranscriptional regulation of ABCA1 and
      macrophage cholesterol efflux. METHODS AND RESULTS: We performed a bioinformatic
      analysis for identifying miRNA target prediction sites in ABCA1 gene and an
      unbiased genome-wide screen to identify miRNAs modulated by cholesterol excess in
      mouse peritoneal macrophages. Quantitative real-time reverse transcription
      polymerase chain reaction confirmed that miR-758 is repressed in cholesterol
      loaded macrophages. Under physiological conditions, high dietary fat excess in
      mice repressed miR-758 both in peritoneal macrophages and, to a lesser extent, in
      the liver. In mouse and human cells in vitro, miR-758 repressed the expression of
      ABCA1, and conversely, the inhibition of this miRNA by using anti-miR-758
      increased ABCA1 expression. In mouse cells, miR-758 reduced cellular cholesterol
      efflux to apolipoprotein A1 (apoA1), and anti-miR-758 increased it. miR-758
      directly targets the 3'-untranslated region of Abca1 as assessed by 3'
      untranslated region luciferase reporter assays. Interestingly, miR-758 is highly
      expressed in the brain, where it also targets several genes involved in
      neurological functions, including Slc38a1, Ntm, Epha7, and Mytl1. CONCLUSION: We
      identified miR-758 as a novel miRNA that posttranscriptionally controls ABCA1
      levels in different cells and regulates macrophage cellular cholesterol efflux to
      apoA1, opening new avenues to increase apoA1 and raise high-density lipoprotein
      levels.

PMID- 21885855
TI  - When prisoners take over the prison: a social psychology of resistance.
AB  - There is a general tendency for social psychologists to focus on processes of
      oppression rather than resistance. This is exemplified and entrenched by the
      Stanford Prison Experiment (SPE). Consequently, researchers and commentators have
      come to see domination, tyranny, and abuse as natural or inevitable in the world
      at large. Challenging this view, research suggests that where members of low
      status groups are bound together by a sense of shared social identity, this can
      be the basis for effective leadership and organization that allows them to
      counteract stress, secure support, challenge authority, and promote social change
      in even the most extreme of situations. This view is supported by a review of
      experimental research--notably the SPE and the BBC Prison Study--and case studies
      of rebellion against carceral regimes in Northern Ireland, South Africa, and Nazi
      Germany. This evidence is used to develop a social identity model of resistance
      dynamics.

PMID- 21885854
TI  - Dysregulated selectin expression and monocyte recruitment during ischemia-related
      vascular remodeling in diabetes mellitus.
AB  - OBJECTIVE: Diabetes mellitus (DM) is associated with impaired ischemia-related
      vascular remodeling and also dysregulation of the inflammatory response. We
      sought to determine whether impaired selectin-mediated monocyte recruitment in
      ischemic tissues contributes to blunted ischemia-mediated angiogenesis in DM.
      METHODS AND RESULTS: Contrast-enhanced ultrasound perfusion imaging and molecular
      imaging of endothelial P-selectin expression in the proximal hindlimb were
      performed at 1, 3, and 21 days after arterial ligation in wild-type and db/db
      mice. Ligation reduced muscle blood flow to ~0.05 mL/minute per gram in both
      strains. Significant recovery of flow occurred only in wild-type mice (60%-65% of
      baseline flow). On molecular imaging, baseline P-selectin signal was 4-fold
      higher in db/db compared with wild-type mice (P<0.01) but increased minimally at
      day 1 after ischemia, whereas signal increased approximately 10-fold in wild-type
      mice (P<0.01). Immunohistology of the hindlimb skeletal muscle demonstrated
      severely reduced monocyte recruitment in db/db mice compared with wild-type mice.
      Local treatment with monocyte chemotactic protein-1 corrected the deficits in
      postischemic P-selectin expression and monocyte recruitment in db/db mice and led
      to greater recovery in blood flow. CONCLUSION: In DM, there is dysregulation of
      the selectin response to limb ischemia, which leads to impaired monocyte
      recruitment, which may be mechanistically related to reduced vascular remodeling
      in limb ischemia.

PMID- 21885856
TI  - Transnational relations between perceived parental acceptance and personality
      dispositions of children and adults: a meta-analytic review.
AB  - Three questions drawn from parental acceptance-rejection theory were addressed:
      (a) Are children's perceptions of parental acceptance transnationally associated
      with specific personality dispositions? (b) Are adults' remembrances of parental
      acceptance in childhood transnationally associated with these personality
      dispositions? and (c) Do relations between parental acceptance and offspring's
      personality dispositions vary by gender of parents? All studies used the child
      and adult versions of the Parental Acceptance-Rejection Questionnaires (PARQ) for
      Mothers and for Fathers, as well as the child and adult versions of the
      Personality Assessment Questionnaire (PAQ). Results showed that both maternal and
      paternal acceptance in childhood correlated significantly in all countries with
      all seven personality dispositions of adult offspring. Adults' remembrance of
      paternal acceptance in childhood correlated significantly with all adult
      personality dispositions except dependence.

PMID- 21885857
TI  - Negativity and outgroup biases in attitude formation and transfer.
AB  - In an initial experiment, the behavior of one person had a stronger influence on
      implicit evaluations of another person from the same group when (a) the attitude
      was negative rather than positive and (b) the people were outgroup members rather
      than ingroup members. Explicitly, participants resisted these attitude transfer
      effects. In a second experiment, negative information formed less negative
      explicit attitudes when the target was Black than when the target was White, and
      participants were more vigilant not to transfer that negative attitude to a new
      Black person. Implicit attitudes, however, transferred to both Black and White
      targets. Positive information formed stronger positive explicit attitudes when
      the target was Black than when the target was White, and that evaluation
      transferred to another Black person both implicitly and explicitly. Even when
      deliberately resisting outgroup negativity in attitude formation and transfer,
      people appear unable to avoid it implicitly.

PMID- 21885858
TI  - Perceived racial discrimination as a barrier to college enrollment for African
      Americans.
AB  - African Americans trail European Americans in terms of academic achievement, even
      when accounting for differences in socioeconomic status. One cause of this gap
      may be racial discrimination. In the current article the authors hypothesized
      that early perceived racial discrimination (by 5th grade) would predict college
      enrollment, mediated by changes from 7th grade to 10th grade in academic
      orientation, college aspirations and expectations, and deviance tolerance.
      Participants were 750 African Americans from the Family and Community Health
      Study. A structural equation model that controlled for socioeconomic status and
      earlier academic performance supported the hypothesis, with the exception that
      discrimination did not influence aspirations. The effect of discrimination on
      expectations, however, was moderated: Participants with high future orientation
      maintained high expectations in spite of discrimination. These results suggest
      that discrimination discourages some African Americans from pursuing higher
      education and that increasing future orientation may promote African Americans'
      college enrollment.

PMID- 21885860
TI  - Social exclusion and pain sensitivity: why exclusion sometimes hurts and
      sometimes numbs.
AB  - Some research indicates that social exclusion leads to increased emotional- and
      physical-pain sensitivity, whereas other work indicates that exclusion causes
      emotional- and physical-pain numbing. This research sought to examine what causes
      these opposing outcomes. In Study 1, the paradigm used to instantiate social
      exclusion was found to moderate the social exclusion-physical pain relation:
      Future-life exclusion led to a numbing of physical pain whereas Cyberball
      exclusion led to hypersensitivity. Study 2 examined the underlying mechanism,
      which was hypothesized to be the severity of the "social injury." Participants
      were subjected to either the standard future-life exclusion manipulation
      (purported to be a highly severe social injury) or a newly created, less-severe
      version. Supporting our hypothesis, the standard (highly severe) future-life
      exclusion led to physical-pain numbing, whereas the less-severe future-life
      exclusion resulted in hypersensitivity. Implications of these results for
      understanding the exclusion-pain relation and other exclusion effects are
      discussed.

PMID- 21885859
TI  - When the seemingly innocuous "stings": racial microaggressions and their
      emotional consequences.
AB  - Commonplace situations that are seemingly innocuous may nonetheless be
      emotionally harmful for racial minorities. In the current article the authors
      propose that despite their apparent insignificance, these situations can be
      harmful and experienced as subtle racism when they are believed to have occurred
      because of their race. In Study 1, Asian Americans reported greater negative
      emotion intensity when they believed that they encountered a situation because of
      their race, even after controlling for other potential social identity
      explanations. Study 2 replicated this finding and confirmed that the effect was
      significantly stronger among Asian Americans than among White participants. These
      findings clarify how perceptions of subtle racial discrimination that do not
      necessarily involve negative treatment may account for the "sting" of racial
      microaggressions, influencing the emotional well-being of racial minorities, even
      among Asian Americans, a group not often expected to experience racism.

PMID- 21885861
TI  - He just wants to play: how goals determine the influence of violent computer
      games on aggression.
AB  - Generally, the accessibility of goal-related constructs is inhibited upon goal
      fulfillment. In line with this notion, the current studies explored whether
      violent computer games may reduce relative accessibility of aggression if the
      game involves the fulfillment of an aggressive goal. Specifically, in Study 1,
      participants who watched a trailer for a violent computer game that fulfilled the
      goal of venting anger showed less relative accessibility of aggression compared
      to participants who watched the trailer without goal fulfillment. In Study 2,
      actually playing a violent computer game to vent anger also decreased the
      relative accessibility of aggression compared to a control condition in which the
      game was played without such a goal. Lastly, in Study 3, the relative
      accessibility of aggression was reduced after playing a violent computer game for
      participants who reported a high general tendency to vent their anger.

PMID- 21885862
TI  - Targeting FGFR/PDGFR/VEGFR impairs tumor growth, angiogenesis, and metastasis by
      effects on tumor cells, endothelial cells, and pericytes in pancreatic cancer.
AB  - Activation of receptor tyrosine kinases, such as fibroblast growth factor
      receptor (FGFR), platelet-derived growth factor receptor (PDGFR), and VEGF
      receptor (VEGFR), has been implicated in tumor progression and metastasis in
      human pancreatic cancer. In this study, we investigated the effects of TKI258, a
      tyrosine kinase inhibitor to FGFR, PDGFR, and VEGFR on pancreatic cancer cell
      lines (HPAF-II, BxPC-3, MiaPaCa2, and L3.6pl), endothelial cells, and vascular
      smooth muscle cells (VSMC). Results showed that treatment with TKI258 impaired
      activation of signaling intermediates in pancreatic cancer cells, endothelial
      cells, and VSMCs, even upon stimulation with FGF-1, FGF-2, VEGF-A, and PDGF-B.
      Furthermore, blockade of FGFR/PDGFR/VEGFR reduced survivin expression and
      improved activity of gemcitabine in MiaPaCa2 pancreatic cancer cells. In
      addition, motility of cancer cells, endothelial cells, and VSMCs was reduced upon
      treatment with TKI258. In vivo, therapy with TKI258 led to dose-dependent
      inhibition of subcutaneous (HPAF-II) and orthotopic (L3.6pl) tumor growth.
      Immunohistochemical analysis revealed effects on tumor cell proliferation
      [bromodeoxyuridine (BrdUrd)] and tumor vascularization (CD31). Moreover, lymph
      node metastases were significantly reduced in the orthotopic tumor model when
      treatment was initiated early with TKI258 (30 mg/kg/d). In established tumors,
      TKI258 (30 mg/kg/d) led to significant growth delay and improved survival in
      subcutaneous and orthotopic models, respectively. These data provide evidence
      that targeting FGFR/PDFGR/VEGFR with TKI258 may be effective in human pancreatic
      cancer and warrants further clinical evaluation.

PMID- 21885863
TI  - A6 peptide activates CD44 adhesive activity, induces FAK and MEK phosphorylation,
      and inhibits the migration and metastasis of CD44-expressing cells.
AB  - The A6 peptide (acetyl-KPSSPPEE-amino) has antitumor activity in the absence of
      significant adverse events in murine tumor models and clinical trials. A6 shares
      sequence homology with CD44, an adhesion receptor involved in metastasis that is
      also a marker of cancer stem cells and drug-resistant phenotypes. We investigated
      the mechanism of action of A6 by examining its effects on CD44 activity, cell
      migration, and metastasis. A6 inhibited the migration of a subset of ovarian and
      breast cancer cell lines, exhibiting IC(50) values of 5 to 110 nmol/L. The
      ability of A6 to inhibit migration in vitro correlated with CD44 expression.
      Immunopreciptation studies showed that CD44 binds A6 and that biotin-tagged A6
      can be cross-linked to CD44. The binding of A6 altered the structure of CD44 such
      that it was no longer recognized by a monoclonal antibody to a specific epitope.
      Importantly, A6 potentiated the CD44-dependent adhesion of cancer cells to
      hyaluronic acid and activated CD44-mediated signaling, as evidenced by focal
      adhesion kinase and MAP/ERK kinase phosphorylation. In vivo, A6 (100 mg/kg
      delivered s.c. twice daily) reduced the number of lung foci generated by the i.v.
      injection of B16-F10 melanoma cells by 50% (P = 0.029 in an unpaired t test). We
      conclude that A6 potently blocks the migration of CD44-positive cells in vitro
      through an interaction with CD44 that alters its structure and activates CD44 to
      enhance ligand binding and downstream signaling. The concurrent ability of A6 to
      agonize the CD44 receptor suggests that CD44 activation may represent a novel
      strategy for inhibiting metastatic disease.

PMID- 21885864
TI  - Discovery and evaluation of inhibitors of human ceramidase.
AB  - The ceramide/sphingosine-1-phosphate (S1P) rheostat has been hypothesized to play
      a critical role in regulating tumor cell fate, with elevated levels of ceramide
      inducing death and elevated levels of S1P leading to survival and proliferation.
      Ceramidases are key enzymes that control this rheostat by hydrolyzing ceramide to
      produce sphingosine and may also confer resistance to drugs and radiation.
      Therefore, ceramidase inhibitors have excellent potential for development as new
      anticancer drugs. In this study, we identify a novel ceramidase inhibitor
      (Ceranib-1) by screening a small molecule library and describe the synthesis of a
      more potent analogue (Ceranib-2). In a cell-based assay, both compounds were
      found to inhibit cellular ceramidase activity toward an exogenous ceramide
      analogue, induce the accumulation of multiple ceramide species, decrease levels
      of sphingosine and S1P, inhibit the proliferation of cells alone and in
      combination with paclitaxel, and induce cell-cycle arrest and cell death. In
      vivo, Ceranib-2 was found to delay tumor growth in a syngeneic tumor model
      without hematologic suppression or overt signs of toxicity. These data support
      the selection of ceramidases as suitable targets for anticancer drug development
      and provide the first nonlipid inhibitors of human ceramidase activity.

PMID- 21885865
TI  - The aurora kinase inhibitor CCT137690 downregulates MYCN and sensitizes MYCN
      amplified neuroblastoma in vivo.
AB  - Aurora kinases regulate key stages of mitosis including centrosome maturation,
      spindle assembly, chromosome segregation, and cytokinesis. Aurora A and B kinase
      overexpression has also been associated with various human cancers, and as such,
      they have been extensively studied as novel antimitotic drug targets. Here, we
      characterize the Aurora kinase inhibitor CCT137690, a highly selective, orally
      bioavailable imidazo[4,5-b]pyridine derivative that inhibits Aurora A and B
      kinases with low nanomolar IC(50) values in both biochemical and cellular assays
      and exhibits antiproliferative activity against a wide range of human solid tumor
      cell lines. CCT137690 efficiently inhibits histone H3 and transforming acidic
      coiled-coil 3 phosphorylation (Aurora B and Aurora A substrates, respectively) in
      HCT116 and HeLa cells. Continuous exposure of tumor cells to the inhibitor causes
      multipolar spindle formation, chromosome misalignment, polyploidy, and apoptosis.
      This is accompanied by p53/p21/BAX induction, thymidine kinase 1 downregulation,
      and PARP cleavage. Furthermore, CCT137690 treatment of MYCN-amplified
      neuroblastoma cell lines inhibits cell proliferation and decreases MYCN protein
      expression. Importantly, in a transgenic mouse model of neuroblastoma that
      overexpresses MYCN protein and is predisposed to spontaneous neuroblastoma
      formation, this compound significantly inhibits tumor growth. The potent
      preclinical activity of CCT137690 suggests that this inhibitor may benefit
      patients with MYCN-amplified neuroblastoma.

PMID- 21885866
TI  - Identification of small-molecule inhibitors of the colorectal cancer oncogene
      Kruppel-like factor 5 expression by ultrahigh-throughput screening.
AB  - The transcription factor Kruppel-like factor 5 (KLF5) is primarily expressed in
      the proliferative zone of the mammalian intestinal epithelium, where it regulates
      cell proliferation. Studies showed that inhibition of KLF5 expression reduces
      proliferation rates in human colorectal cancer cells and intestinal tumor
      formation in mice. To identify chemical probes that decrease levels of KLF5, we
      used cell-based ultrahigh-throughput screening (uHTS) to test compounds in the
      public domain of NIH, the Molecular Libraries Probe Production Centers Network
      library. The primary screen involved luciferase assays in the DLD-1/pGL4.18hKLF5p
      cell line, which stably expressed a luciferase reporter driven by the human KLF5
      promoter. A cytotoxicity counterscreen was done in the rat intestinal epithelial
      cell line, IEC-6. We identified 97 KLF5-selective compounds with EC(50) < 10
      MUmol/L for KLF5 inhibition and EC(50) > 10 MUmol/L for IEC-6 cytotoxicity. The
      two most potent compounds, CIDs (PubChem Compound IDs) 439501 and 5951923, were
      further characterized on the basis of computational, Western blot, and cell
      viability analyses. Both of these compounds, and two newly synthesized structural
      analogs of CID 5951923, significantly reduced endogenous KLF5 protein levels and
      decreased viability of several colorectal cancer cell lines without any apparent
      impact on IEC-6 cells. Finally, when tested in the NCI-60 panel of human cancer
      cell lines, compound CID 5951923 was selectively active against colon cancer
      cells. Our results show the feasibility of uHTS in identifying novel compounds
      that inhibit colorectal cancer cell proliferation by targeting KLF5.

PMID- 21885867
TI  - Chronic stroke survivors benefit from high-intensity aerobic treadmill exercise:
      a randomized control trial.
AB  - BACKGROUND AND OBJECTIVE: Ambulatory subjects after stroke may benefit from gait
      oriented cardiovascular fitness training, but trials to date have not primarily
      assessed older persons. METHODS: Thirty-eight subjects (age >60 years) with
      residual hemiparetic gait were enrolled >6 months after stroke. Participants were
      randomized to receive 3 months (3*/week) progressive graded, high-intensity
      aerobic treadmill exercise (TAEX) or conventional care physiotherapy. Primary
      outcome measures were peak exercise capacity (Vo(2peak)) and sustained walking
      capacity in 6-minute walks (6MW). Secondary measures were gait velocity in 10-m
      walks, Berg Balance Scale, functional leg strength (5 chair-rise), self-rated
      mobility (Rivermead Mobility Index), and quality of life (SF-12). RESULTS: Thirty
      six participants completed the study (18 TAEX, 18 controls). TAEX but not
      conventional care improved Vo(2peak) (difference 6.4 mL/kg/min, P < .001) and 6MW
      (53 m, P < .001). Likewise, maximum walking speed (0.13 m/s, P = .01), balance (P
      < .05), and the mental subscore of the SF-12 (P < .01) improved more after TAEX.
      Gains in Vo(2peak) correlated with the degree at which training intensity could
      be progressed in the individual participant (P < .01). Better walking was related
      to progression in treadmill velocity and training duration (P < .001). Vo(2peak)
      and 6MW performances were still higher 1 year after the end of training when
      compared with the baseline, although endurance walking (6MW) at 1 year was lower
      than immediately after training (P < .01). CONCLUSION: This trial demonstrates
      that TAEX effectively improves cardiovascular fitness and gait in persons with
      chronic stroke.

PMID- 21885868
TI  - Targeting curcusomes to inflammatory dendritic cells inhibits NF-kappaB and
      improves insulin resistance in obese mice.
AB  - OBJECTIVE: To determine whether and by what mechanism systemic delivery of
      curcumin-containing liposomes improves insulin resistance in the leptin deficient
      (ob/ob) mouse model of insulin resistance. RESEARCH DESIGN AND METHODS: Insulin
      resistant ob/ob mice with steatosis were injected intraperitoneally with liposome
      nanoparticles, entrapping the nuclear factor-kappaB (NF-kappaB) inhibitor
      curcumin (curcusomes), and uptake in liver and adipose tissue was determined by
      flow cytometry. The effects of curcusomes on macrophage NF-kappaB activation and
      cytokine production were assessed. Transfer experiments determined the role of
      hepatic tumor necrosis factor (TNF)/inducible nitric oxide synthase-producing
      dendritic cells (Tip-DCs) and adipose tissue macrophages (ATMs) in inflammation
      induced insulin resistance, determined by homeostatic assessment of insulin
      resistance. RESULTS: Phagocytic myeloid cells infiltrating the liver in ob/ob
      mice had the phenotypic characteristics of Tip-DCs that arise from monocyte
      precursors in the liver and spleen after infection. Targeting Tip-DCs and ATMs
      with curcusomes in ob/ob mice reduced NF-kappaB/RelA DNA binding activity,
      reduced TNF, and enhanced interleukin-4 production. Curcusomes improved
      peripheral insulin resistance. CONCLUSIONS: Both hepatic Tip-DCs and ATMs
      contribute to insulin resistance in ob/ob mice. Curcusome nanoparticles inhibit
      proinflammatory pathways in hepatic Tip-DCs and ATMs and reverse insulin
      resistance. Targeting inflammatory DCs is a novel approach for type 2 diabetes
      treatment.

PMID- 21885869
TI  - CCK stimulation of GLP-1 neurons involves alpha1-adrenoceptor-mediated increase
      in glutamatergic synaptic inputs.
AB  - OBJECTIVE: Glucagon-like peptide 1 (GLP-1) is involved in the central regulation
      of food intake. It is produced within the brain by preproglucagon (PPG) neurons,
      which are located primarily within the brain stem. These neurons project widely
      throughout the brain, including to the appetite centers in the hypothalamus, and
      are believed to convey signals related to satiety. Previous work demonstrated
      that they are directly activated by leptin and electrical activity of the
      afferent vagus. Another satiety hormone, cholecystokinin (CCK), has also been
      linked to activation of brain stem neurons, suggesting that it might act
      partially via centrally projecting neurons from the nucleus tractus solitarius
      (NTS). The aim of this study was to investigate the neuronal circuitry linking
      CCK to the population of NTS-PPG neurons. RESEARCH DESIGN AND METHODS: Transgenic
      mice expressing yellow fluorescent protein (Venus) under the control of the PPG
      promoter were used to identify PPG neurons in vitro and to record their
      electrical and pharmacological profile. RESULTS: PPG neurons in the NTS were
      excited by CCK and epinephrine, but not by the melanocortin receptor agonist
      melanotan II. Both CCK and epinephrine acted to increase glutamatergic
      transmission to the PPG neurons, and this involved activation of alpha(1)
      adrenergic receptors. Inhibition of adrenergic signaling abolished the excitatory
      action of CCK. CONCLUSIONS: CCK activates NTS-PPG cells by a circuit involving
      adrenergic and glutamatergic neurons. NTS-PPG neurons integrate a variety of
      peripheral signals that indicate both long-term energy balance and short-term
      nutritional and digestional status to produce an output signal to feeding and
      autonomic circuits.

PMID- 21885870
TI  - Mechanisms of control of the free Ca2+ concentration in the endoplasmic reticulum
      of mouse pancreatic beta-cells: interplay with cell metabolism and [Ca2+]c and
      role of SERCA2b and SERCA3.
AB  - OBJECTIVE: Sarco-endoplasmic reticulum Ca(2+)-ATPase 2b (SERCA2b) and SERCA3 pump
      Ca(2+) in the endoplasmic reticulum (ER) of pancreatic beta-cells. We studied
      their role in the control of the free ER Ca(2+) concentration ([Ca(2+)](ER)) and
      the role of SERCA3 in the control of insulin secretion and ER stress. RESEARCH
      DESIGN AND METHODS: beta-Cell [Ca(2+)](ER) of SERCA3(+/+) and SERCA3(-/-) mice
      was monitored with an adenovirus encoding the low Ca(2+)-affinity sensor D4
      addressed to the ER (D4ER) under the control of the insulin promoter. Free
      cytosolic Ca(2+) concentration ([Ca(2+)](c)) and [Ca(2+)](ER) were simultaneously
      recorded. Insulin secretion and mRNA levels of ER stress genes were studied.
      RESULTS: Glucose elicited synchronized [Ca(2+)](ER) and [Ca(2+)](c) oscillations.
      [Ca(2+)](ER) oscillations were smaller in SERCA3(-/-) than in SERCA3(+/+) beta
      cells. Stimulating cell metabolism with various [glucose] in the presence of
      diazoxide induced a similar dose-dependent [Ca(2+)](ER) rise in SERCA3(+/+) and
      SERCA3(-/-) beta-cells. In a Ca(2+)-free medium, glucose moderately raised
      [Ca(2+)](ER) from a highly buffered cytosolic Ca(2+) pool. Increasing [Ca(2+)](c)
      with high [K] elicited a [Ca(2+)](ER) rise that was larger but more transient in
      SERCA3(+/+) than SERCA3(-/-) beta-cells because of the activation of a Ca(2+)
      release from the ER in SERCA3(+/+) beta-cells. Glucose-induced insulin release
      was larger in SERCA3(-/-) than SERCA3(+/+) islets. SERCA3 ablation did not induce
      ER stress. CONCLUSIONS: [Ca(2+)](c) and [Ca(2+)](ER) oscillate in phase in
      response to glucose. Upon [Ca(2+)](c) increase, Ca(2+) is taken up by SERCA2b and
      SERCA3. Strong Ca(2+) influx triggers a Ca(2+) release from the ER that depends
      on SERCA3. SERCA3 deficiency neither impairs Ca(2+) uptake by the ER upon cell
      metabolism acceleration and insulin release nor induces ER stress.

PMID- 21885871
TI  - miR-146a-Mediated extracellular matrix protein production in chronic diabetes
      complications.
AB  - OBJECTIVE: MicroRNAs (miRNAs), through transcriptional regulation, modulate
      several cellular processes. In diabetes, increased extracellular matrix protein
      fibronectin (FN) production is known to occur through histone acetylator p300.
      Here, we investigated the role of miR-146a, an FN-targeting miRNA, on FN
      production in diabetes and its relationship with p300. RESEARCH DESIGN AND
      METHODS: miR-146a expressions were measured in endothelial cells from large
      vessels and retinal microvessels in various glucose levels. FN messenger RNA
      expression and protein levels with or without miR-146a mimic or antagomir
      transfection were examined. A luciferase assay was performed to detect miR-146a's
      binding to FN 3'-untranslated region (UTR). Likewise, retinas from type 1
      diabetic rats were studied with or without an intravitreal injection of miR-146a
      mimic. In situ hybridization was used to localize retinal miR-146a. Cardiac and
      renal tissues were analyzed from type 1 and type 2 diabetic animals. RESULTS: A
      total of 25 mmol/L glucose decreased miR-146a expression and increased FN
      expression compared with 5 mmol/L glucose in both cell types. miR-146a mimic
      transfection prevented such change, whereas miR-146a antagomir transfection in
      the cells in 5 mmol/L glucose caused FN upregulation. A luciferase assay
      confirmed miR-146a's binding to FN 3'-UTR. miR-146a was localized in the retinal
      endothelial cells and was decreased in diabetes. Intravitreal miR-146a mimic
      injection restored retinal miR-146a and decreased FN in diabetes. Additional
      experiments showed that p300 regulates miR-146a. Similar changes were seen in the
      retinas, kidneys, and hearts in type 1 and type 2 diabetic animals. CONCLUSIONS:
      These studies showed a novel, glucose-induced molecular mechanism in which miR
      146a participates in the transcriptional circuitry regulating extracellular
      matrix protein production in diabetes.

PMID- 21885872
TI  - Hepatic glucagon action is essential for exercise-induced reversal of mouse fatty
      liver.
AB  - OBJECTIVE: Exercise is an effective intervention to treat fatty liver. However,
      the mechanism(s) that underlie exercise-induced reductions in fatty liver are
      unclear. Here we tested the hypothesis that exercise requires hepatic glucagon
      action to reduce fatty liver. RESEARCH DESIGN AND METHODS: C57BL/6 mice were fed
      high-fat diet (HFD) and assessed using magnetic resonance, biochemical, and
      histological techniques to establish a timeline for fatty liver development over
      20 weeks. Glucagon receptor null (gcgr(-/-)) and wild-type (gcgr(+/+)) littermate
      mice were subsequently fed HFD to provoke moderate fatty liver and then performed
      either 10 or 6 weeks of running wheel or treadmill exercise, respectively.
      RESULTS: Exercise reverses progression of HFD-induced fatty liver in gcgr(+/+)
      mice. Remarkably, such changes are absent in gcgr(-/-) mice, thus confirming the
      hypothesis that exercise-stimulated hepatic glucagon receptor activation is
      critical to reduce HFD-induced fatty liver. CONCLUSIONS: These findings suggest
      that therapies that use antagonism of hepatic glucagon action to reduce blood
      glucose may interfere with the ability of exercise and perhaps other
      interventions to positively affect fatty liver.

PMID- 21885873
TI  - Hyalinization of the pyloric stomach in CD-1 mice following oral (dietary)
      administration of the corticosteroid agonists mometasone furoate, budesonide, and
      flunisolide.
AB  - The purpose of this study was to compare the toxicity of three marketed
      corticosteroid receptor agonists (mometasone furoate, budesonide, or flunisolide)
      to the stomach of female CD-1 mice following oral administration via the diet for
      up to 52 weeks, with a 16-week recovery period (budesonide and flunisolide). A
      range of tissues was examined by light microscopy, accompanied by clinical
      pathology measurements to assess anticipated corticosteroid effects as a
      surrogate marker of systemic drug exposure. Microscopic changes seen in the
      stomach with each corticosteroid included pyloric hyalinization. This previously
      unreported finding was investigated using histochemical and immunohistochemical
      techniques and was found to consist of hyalinized collagen, in association with
      increased immunohistochemical signal for transglutaminase-2 and osteopontin. The
      significance of the osteopontin finding is unclear; however, the ability of
      transglutaminase-2 to facilitate the formation of degradation resistant protein
      bonds implies this protein may be involved in the pathogenesis of this change.
      Furthermore, published evidence that transglutaminase-2 may be induced by a
      corticosteroid agonist raises the possibility that pyloric stomach hyalinization
      may be a class effect of corticosteroids via the action of this enzyme.

PMID- 21885874
TI  - Role of quercetin in preventing thioacetamide-induced liver injury in rats.
AB  - In hepatic toxicity induced in rats by two injections of thioacetamide (TAA, 350
      mg/kg with an interval of 8 hr), the action of quercetin was investigated. After
      96 hr, TAA administration resulted in hepatic necrosis, significant increases in
      serum transaminase activity, and increases in hepatic lipoperoxidation.
      Thioacetamide-induced hepatotoxicity also showed changes in antioxidant enzymes
      in the liver of rats, with alterations in p-ERK 1/2 (phosphorylated extracellular
      signal related kinase 1/2) as well as an imbalance between proapototic protein
      Bax and anti-apoptotic protein Bcl-2 expression. With administration of the
      flavonoid quercetin (50 mg/Kg i.p.) for four consecutive days following TAA,
      serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
      activity were close to normal values in rats. Histological findings suggested
      that quercetin had a preventive effect on TAA-induced hepatic necrosis. Quercetin
      treatment caused significant decreases in lipid peroxide levels in the TAA
      treated rats, with some changes in antioxidant enzymes superoxide dismutase
      (SOD), catalase (CAT), and glutathione peroxidase (GPx). Quercetin also inhibited
      the change of the p-ERK1/2 by TAA and significantly prevented the increase in
      Bax/Bcl-2 ratio, thus preventing apoptosis. Findings indicate that quercetin may
      have a preventive effect on TAA-induced hepatotoxicity by modulating the
      oxidative stress parameters and apoptosis pathway.

PMID- 21885875
TI  - Malignancies associated with tumour necrosis factor inhibitors in registries and
      prospective observational studies: a systematic review and meta-analysis.
AB  - OBJECTIVES: This project was undertaken to assess the risk of malignancy in
      patients with rheumatoid arthritis treated with tumour necrosis factor inhibitors
      (TNFi) in clinical practice, as recorded in prospective, observational studies.
      METHODS: The authors undertook comprehensive searches of MEDLINE, EMBASE, the
      Cochrane Database of Systematic Reviews and American College of Rheumatology,
      European League against Rheumatism and British Society for Rheumatology
      conference abstracts according to a prespecified protocol. RESULTS: The searches
      identified 2039 full-text papers and 1979 conference abstracts, of which 21 full
      texts and eight abstracts met the inclusion criteria. The pooled estimate for the
      risk of all-site malignancy from seven studies was 0.95 (95% CI 0.85 to 1.05).
      Two studies reported there was no evidence that longer exposure to TNFi agents
      increased the risk of malignancy. In patients with previous malignancies there
      was a higher risk of a new/recurring malignancy. This risk was not increased
      further by exposure to TNFi, although CI were wide. Results from four studies
      showed that patients treated with TNFi have a significantly increased risk of
      developing a non-melanoma skin cancer (1.45, 95% CI 1.15 to 1.76). In addition,
      patients are at an increased risk of developing melanoma, as the pooled estimate
      from two studies was 1.79 (95% CI 0.92 to 2.67). The pooled estimate for the risk
      of lymphoma was 1.11 (95% CI 0.70 to 1.51). CONCLUSIONS: This systematic review
      and meta-analysis shows that TNFi treatments do not increase the risk of
      malignancy, particularly lymphoma. However, they do appear to increase the risk
      of skin cancer, including melanoma.

PMID- 21885876
TI  - The significance of early alpha-fetoprotein level changes in predicting clinical
      and survival benefits in advanced hepatocellular carcinoma patients receiving
      sorafenib.
AB  - BACKGROUND: he role of serum alpha-fetoprotein (AFP) changes in predicting the
      treatment outcomes of advanced hepatocellular carcinoma (HCC) patients to
      sorafenib remains unknown. METHODS: Serum AFP was collected prospectively at
      baseline and subsequent follow-up visits in parallel with clinical and survival
      outcomes. AFP response was defined as a relative drop of AFP >20% of the baseline
      level after 6 weeks of sorafenib. The relationship between AFP response and the
      treatment outcomes was first explored in patients who received sorafenib in a
      phase II study. Subsequently, an independent validation set of patients were
      obtained to validate the association of AFP response to clinical outcomes.
      RESULTS: Included in the exploration and validation sets for analysis were 41 and
      53 patients, respectively, with baseline AFP level >20 MUg/L. In the exploration
      cohort, AFP response was significantly associated with clinical benefit (CB) rate
      (relative chance 3.4, 95% confidence interval [CI], 1.1-11.1), and multivariate
      analysis indicated that AFP response was associated with significantly better
      progression-free survival (PFS) (hazard ratio [HR], 0.31; 95% CI, 0.13-0.76) and
      marginally better overall survival (OS) (HR, 0.30; 95% CI, 0.09-1.02). When
      applying AFP changes in the validation set, significant associations were again
      found between AFP response with CB rate (relative chance, 5.5; 95% CI, 2.3-13.6)
      and PFS (HR, 0.12; 95% CI, 0.04-0.30) but not OS (HR, 0.61; 95% CI, 0.27-1.26).
      CONCLUSION: Drop in AFP level at 6 weeks is an exploratory early surrogate for
      both CB and PFS in advanced HCC patients receiving sorafenib.

PMID- 21885877
TI  - Polynucleotide kinase and aprataxin-like forkhead-associated protein (PALF) acts
      as both a single-stranded DNA endonuclease and a single-stranded DNA 3'
      exonuclease and can participate in DNA end joining in a biochemical system.
AB  - Polynucleotide kinase and aprataxin-like forkhead-associated protein (PALF, also
      called aprataxin- and PNK-like factor (APLF)) has been shown to have nuclease
      activity and to use its forkhead-associated domain to bind to x-ray repair
      complementing defective repair in Chinese hamster cells 4 (XRCC4). Because XRCC4
      is a key component of the ligase IV complex that is central to the nonhomologous
      DNA end joining (NHEJ) pathway, this raises the possibility that PALF might play
      a role in NHEJ. For this reason, we further studied the nucleolytic properties of
      PALF, and we searched for any modulation of PALF by NHEJ components. We verified
      that PALF has 3' exonuclease activity. However, PALF also possesses single
      stranded DNA endonuclease activity. This single-stranded DNA endonuclease
      activity can act at all single-stranded sites except those within four
      nucleotides 3' of a double-stranded DNA junction, suggesting that PALF minimally
      requires approximately four nucleotides of single-strandedness. Ku, DNA-dependent
      protein kinase catalytic subunit, and XRCC4-DNA ligase IV do not modulate PALF
      nuclease activity on single-stranded DNA or overhangs of duplex substrates. PALF
      does not open DNA hairpins. However, in a reconstituted end joining assay that
      includes Ku, XRCC4-DNA ligase IV, and PALF, PALF is able to resect 3' overhanging
      nucleotides and permit XRCC4-DNA ligase IV to complete the joining process in a
      manner that is as efficient as Artemis. Reduction of PALF in vivo reduces the
      joining of incompatible DNA ends. Hence, PALF can function in concert with other
      NHEJ proteins.

PMID- 21885878
TI  - Domain-specific physical activity and self-report bias among low-income Latinas
      living in San Diego County.
AB  - BACKGROUND: Evidence suggests that Latina women appear to be less physically
      active than women of other racial/ethnic groups. This study evaluated how
      different domains of physical activity (PA) contributed to overall levels of PA
      among low-income Latinas, the validity of Latinas' self-reported PA, and
      potential moderators of self-report bias in PA. METHODS: A community sample of
      105 Latinas (mean age = 35.9 +/- 9.0 years; mean body mass index = 31.6 +/- 7.2)
      completed the long form Spanish-language version of the International Physical
      Activity Questionnaire (IPAQ), wore an accelerometer for seven days, and
      completed self-reported measures of acculturation and socioeconomic status.
      RESULTS: Ninety-six percent of IPAQ-reported moderate-intensity PA (MPA) was
      accrued during household activities, with only 4% accrued during leisure time.
      Seventy-two percent of participants met national recommendations for PA using
      IPAQ data, but only 20% met recommendations when measured by accelerometer. When
      bouts of MPA lasting >10 min were included, 0% met recommendations. Age appeared
      to moderate self-report bias of vigorous PA, and there were nonsignificant trends
      for acculturation and income to moderate MPA and vigorous-intensity PA,
      respectively. CONCLUSIONS: Data suggest that it is important to measure household
      activity of Latinas, and that the IPAQ yield overestimates of self-report PA.

PMID- 21885879
TI  - Leisure-time physical activity among adult and elderly individuals in Brazil: a
      countrywide analysis.
AB  - BACKGROUND: No data on leisure-time physical activity (LTPA) are available in
      Brazil for a representative sample of the whole country. The current study
      describes LTPA levels of the Brazilian adult and elderly populations and explores
      its association with sex, age, and schooling. METHODS: A countrywide household
      based cross-sectional study was carried out, including separate samples of adult
      and elderly individuals from 23 states in Brazil selected through a multistage
      approach. LTPA was assessed using the long version of the International Physical
      Activity Questionnaire. A cut-off point of 150 minutes per week was used.
      RESULTS: 12,402 adult and 6617 elderly individuals were interviewed in 100
      cities. The proportion of individuals below the 150 minutes per week threshold in
      terms of LTPA was 82.6% (95% CI 81.9; 83.2) among the adults and 86.5% (95% CI
      85.7; 87.3) among elderly individuals. Among adults, prevalence estimates were
      very consistent across regions. Elderly subjects living in states in the
      Northeast and North regions of the country were less active than those from the
      other regions. A clear positive dose-response association was observed between
      LTPA and schooling. CONCLUSION: Alarming rates of low levels of LTPA are found in
      Brazil, thus suggesting the need of urgent actions.

PMID- 21885881
TI  - Meeting physical activity recommendations for colon cancer prevention among
      Japanese adults: prevalence and sociodemographic correlates.
AB  - BACKGROUND: Although physical activity is associated with a lower risk of colon
      cancer, few studies have described the physical activity required for colon
      cancer prevention in various sociodemographic subgroups. The current study
      examined the prevalence and sociodemographic correlates of attaining the 2
      recommended physical activity criteria for colon cancer prevention among Japanese
      adults. METHODS: The sample included 5322 Japanese adults aged 20 to 79 years.
      Seven sociodemographic attributes (eg, gender, age, education level, employment
      status) and the International Physical Activity Questionnaire were assessed via
      an Internet-based survey. The odds of meeting each physical activity criterion by
      sociodemographic variables were calculated. RESULTS: Overall, 23.8% of the study
      population met the criterion of >= 420 minutes of moderate-intensity activity,
      and 6.4% met the criterion of >= 210 minutes of vigorous activity. Being male,
      highly educated, employed, living with another person, being married and having a
      higher household income were significantly correlated with the attainment of
      recommendations. CONCLUSIONS: Participants who met the 2 activity recommendations
      differed in gender, education level, employment status, marital status, living
      conditions, and household income. The findings of the current study imply that
      strategies to promote more intense physical activity in all demographic groups
      may be necessary.

PMID- 21885880
TI  - Walking for transportation among Latino adults in San Diego County: who meets
      physical activity guidelines?
AB  - BACKGROUND: U.S. Latinos engage in nonleisure-time walking (NLTW) more than other
      ethno-racial groups. Studies are needed to explore factors associated with NLTW
      to inform interventions for effective physical activity promotion. PURPOSE: To
      examine the social-ecological correlates of NLTW among Mexican-origin Latinos.
      METHODS: Individual, social, and environmental level factors and PA were assessed
      in a telephone survey completed by 672 Mexican-origin adults randomly sampled in
      San Diego County. Data were collected in 2006 and analyzed in 2009. RESULTS:
      Participants were mostly female (71%), with an average age of 39 years. Less than
      one-third met PA guidelines for NLTW (29%). Structural equation modeling showed
      that NLTW was positively associated with being female, but negatively associated
      with living in the U.S. >= 12 years, and being U.S.-born. CONCLUSIONS: In this
      sample NLTW differed by various indicators of acculturation and gender. These
      findings might help inform the development of interventions to promote NLTW and
      thus physical activity in Mexican-origin adults.

PMID- 21885882
TI  - Perceived barriers to exercise in Hispanic adults by level of activity.
AB  - BACKGROUND: National data show that Hispanics report low levels of physical
      activity. Limited information on barriers to exercise in this population exists
      in the literature. METHODS: Surveys were administered to 398 Hispanic
      participants from two colonias in South Texas to investigate self-reported levels
      of and perceived barriers to exercise. One-way ANOVA by level of activity and t
      tests by gender were conducted. Exploratory factor analysis was used to examine
      patterns by level of activity. RESULTS: Results show that 67.6% of respondents
      did not meet physical activity recommendations of at least 150 minutes per week,
      as compared with 55.6% nationally. Overall, the most frequently reported barriers
      included "lack of time," "very tired," and "lack of self-discipline" to exercise.
      An exploratory factor analysis of the barriers reported by participants not
      meeting physical activity recommendations resulted in a 3-factor structure. A
      unidimensional scale was found for participants meeting recommendations.
      CONCLUSIONS: Findings suggest that future interventions should be specific to
      gender and exercise level to address the high prevalence of inactivity in this
      population.

PMID- 21885883
TI  - Factors associated with active commuting to school and to work among Brazilian
      adolescents.
AB  - BACKGROUND: Active commuting has decreased substantially in recent decades and
      has been more frequent in specific demographic and socioeconomic profiles. The
      objective of this study was to describe the prevalence of active trips and the
      possible associations with demographic and socioeconomic variables. METHODS: A
      questionnaire on lifestyle and risk behavior was administered to a sample
      population of 5028 adolescents, ages 15 to 19 years, attending public high
      schools in the state of Santa Catarina, Brazil. Logistic regressions (odds ratio-
      OR; 95% confidence interval) were used to test associations. RESULTS: Active
      commuting to school was reported for 56.7% of students, and active commuting to
      work was reported for 70.0%. The likelihood of commuting passively was greater
      among girls (school: OR = 1.27; 1.10-1.45), older adolescents (school: OR = 1.17;
      1.02-1.33; work: OR = 1.49; 1.22-1.82), those who lived in rural areas (school:
      OR = 12.1; 9.91-14.8), those who spent more time in commuting (school: OR = 2.33;
      2.01-2.69; work: OR = 4.35; 3.52-5.38), and those from high-income families
      (school: OR = 1.40; 1.21-1.62; work: OR = 1.69; 1.37-2.08). CONCLUSIONS: The
      proportion of students taking active trips was higher when going to work than to
      school. All indicators were associated with the mode of commuting, except gender
      and place of residence for commuting to work.

PMID- 21885884
TI  - The effects of daily weather on accelerometer-measured physical activity.
AB  - BACKGROUND: This study analyzes Chicago-area weather effects on objectively
      measured physical activity over a 3-year period among a cohort of 241
      participants in an on-going arthritis physical activity trial. METHODS: Uniaxial
      accelerometer counts and interview data were analyzed for up to 6 weekly study
      waves involving 4823 days of wear. The effects of temperature, rainfall, snowfall
      and daylight hours were analyzed after controlling for participant
      characteristics, day of the week, and daily accelerometer wear hours in a mixed
      effects linear regression model. RESULTS: Daylight hours, mean daily temperature
      < 20 or >= 75 degrees, and light or heavy rainfall (but not snowfall) were all
      significantly associated with lower physical activity after controlling for the
      significant effects of weekends, accelerometer wear hours, age, sex, type of
      arthritis, employment, Hispanic ethnicity, obesity, and SF36 physical and mental
      health scores. CONCLUSIONS: The cumulative effects of weather are reflected in a
      38.3% mean monthly difference in daily counts between November and June,
      reflecting over 3 additional hours of sedentary time. Physical activity promotion
      programs for older persons with chronic conditions need lifestyle physical
      activity plans adapted to weather extremes.

PMID- 21885885
TI  - The effects of a supplemental, theory-based physical activity counseling
      intervention for adults with type 2 diabetes.
AB  - BACKGROUND: Physical activity (PA) is a cornerstone in the management of type 2
      diabetes (T2DM). This pilot investigation explores the effects of a standard
      diabetes education program compared with a supplemental PA intervention on
      diabetes-related health outcomes. METHODS: Using a prospective 2-armed design, 96
      adults with T2DM were randomly assigned to either standard care (diabetes
      education program; n = 49) or standard care supplemented with an 8-week,
      individualized-counseling and community-based PA component (n = 47). Measurements
      were taken at baseline, 3, 6, and 12 months. Primary outcomes were changes in PA
      (self-report) and HbA1c. Between group changes were compared using analysis of
      covariance (ANCOVA) and changes over time using repeated-measures ANOVA. RESULTS:
      In comparison with standard care, the supplemental group demonstrated an increase
      in PA (Ps < 0.01) and cardiorespiratory fitness (Ps < 0.05) from baseline to all
      follow-up time-points. HbA1c levels declined (P < .05) from baseline to all time
      points in the standard care group. Reduction in cholesterol-ratio (P < .01),
      increase in HDL (P < .05), and reductions in blood pressure, resting heart rate
      and BMI (approaching statistical significance Ps < 0.10) were also reported for
      both groups. CONCLUSIONS: PA counseling in addition to standard care is effective
      for promoting PA behavior change and positive health-related outcomes among
      individuals with T2DM.

PMID- 21885886
TI  - Feasibility of institutional registry-based recruitment for enrolling newly
      diagnosed breast cancer patients in an exercise trial.
AB  - BACKGROUND: The purpose of this study was to determine the feasibility of using a
      tumor registry to recruit newly diagnosed survivors into a randomized controlled
      exercise trial and to discuss issues related to this recruitment strategy.
      METHODS: A tumor registry-based rapid ascertainment system was used to recruit
      breast cancer survivors into a 6-month home-based, telephone-administered
      intervention of moderate-to-vigorous intensity exercise or a usual care group.
      RESULTS: 468 newly diagnosed cases were identified. Of these, 50 women (15.4% of
      those for which screening calls were made) were enrolled in the study. Women were
      randomized, on average, 11 weeks after diagnosis (SD = 4.8). Sixty-four percent
      were randomized before beginning treatment or within the first week of treatment.
      Time required to obtain physician consent was the primary determinant of
      diagnosis-to-randomization latency. Enrolled women were more likely than
      nonenrolled women to be non-Hispanic White and to have a college degree (P <
      .05). CONCLUSION: Tumor registries present a feasible means of recruiting breast
      cancer survivors before or early in adjuvant treatment. The success of recruiting
      survivors promptly after diagnosis is largely dependent on ability to rapidly
      obtain physician consent. Specific effort is needed to counteract self-selection
      effects that may lead to under-representation of minorities.

PMID- 21885887
TI  - The association between physical education and symptoms of attention deficit
      hyperactivity disorder.
AB  - OBJECTIVE: The purpose of the current study was to examine the association
      between structured physical activity, specifically physical education, and
      symptoms of Attention Deficit Hyperactivity Disorder (ADHD). Physical activity
      may be associated with lower levels of symptoms of ADHD and this rationale
      provided the impetus for the current study. METHODS: A community-based,
      nationally representative sample of children from the Early Childhood
      Longitudinal Study, Kindergarten cohort (ECLS-K) was used. Structural equation
      modeling was used to examine the association of physical activity with symptoms
      of Attention Deficit Hyperactivity Disorder. Two random subsamples were drawn for
      the purposes of cross-validation of our model. Statistics reflecting model fit
      are reported. RESULTS: With a standardized path coefficient value of -.23,
      findings from the current study indicate a significant, inverse association
      between physical education, as a structured form of physical activity, with the
      symptoms of Attention Deficit Hyperactivity Disorder in children. CONCLUSIONS:
      Using a community-based, nationally representative sample of children aged 5 to 7
      years old from the United States, the results of the current study suggest that
      physical education, as a structured form of physical activity, may be considered
      as associated with lower levels of symptoms of ADHD across time.

PMID- 21885889
TI  - Psychological responses to acute exercise in sedentary black and white
      individuals.
AB  - BACKGROUND: Racial differences in psychological determinants of exercise exist
      between non-Hispanic blacks (blacks) and non-Hispanic whites (whites). To date,
      no study has examined racial differences in the psychological responses during
      and after exercise. The objective of this study was to compare psychological
      outcomes of single exercise bouts in blacks and whites. METHODS: On 3 separate
      occasions, sedentary black (n = 16) and white (n = 14) participants walked on a
      treadmill at 75%(max HR) for 75 minutes. Questionnaires assessing mood, state
      anxiety, and exercise task self-efficacy were administered before and after each
      exercise bout. In-task mood and rating of perceived exertion (RPE) were measured
      every 5 minutes during exercise. RESULTS: Exercise self-efficacy and
      psychological distress significantly improved in both blacks and whites. However
      during exercise blacks reported more positive in-task mood and lower RPE compared
      with whites. CONCLUSIONS: These data suggest that racial differences exist in
      psychological responses during exercise. Further research should confirm these
      findings in a larger, free-living population.

PMID- 21885888
TI  - Association between school- and nonschool-based activity programs and physical
      activity in adolescent girls.
AB  - BACKGROUND: Some researchers have questioned if activity programs would be more
      effective if based outside school (eg, community leagues) rather than within
      schools. This study compared participation in activity programs based within and
      outside of school, and estimated the associations between participation and
      moderate-vigorous physical activity (MVPA) among adolescent girls. METHODS:
      Within the Trial of Activity for Adolescent Girls, independent samples of 1559
      6th-grade girls (age 11 to 12) and 3282 8th-grade girls (age 13 to 14) reported
      program participation using questionnaires. MVPA was measured using
      accelerometers. Linear mixed models accounted for school and site clustering.
      RESULTS: Sixth-grade girls reported 5 times as many programs outside school as
      within school (4.1 vs. 0.8); daily MVPA was 0.29 minutes higher (1.2% of the
      mean) for each additional program outside school. Compared with 6th-grade girls,
      8th-grade girls participated in 1.3 fewer programs outside school, while
      programs' association with MVPA was unchanged. Conversely, school programs'
      association with MVPA was greater in 8th grade. Daily MVPA was 1.33 minutes
      higher per school program, and participation declined 0.13. CONCLUSION: Programs
      within and outside schools can both increase activity among adolescent girls.
      Intervention research should focus on increasing participation in school
      programs, and increasing movement during programs outside school.

PMID- 21885890
TI  - Postpartum physical activity in overweight and obese women.
AB  - BACKGROUND: Low physical activity (PA) during the postpartum period is associated
      with weight retention. While patterns of PA have been examined in normal weight
      women during this period, little is known about PA among overweight and obese
      women. The aim of this cross-sectional study was to investigate PA and determine
      the proportion of women meeting recommendations for PA. METHODS: Women (n = 491),
      with a body mass index (BMI) >= 25 kg/m2 were enrolled in a behavioral
      intervention. PA was assessed at six weeks postpartum using the Seven-Day PA
      Recall. RESULTS: Women averaged 923 +/- 100 minutes/day of sedentary/ light and
      33 +/- 56 minutes/day of combined moderate, hard, and very hard daily activity.
      Women with a BMI >= 40 kg/m2 reported more time in sedentary/light activities and
      less hours of sleep than those with a lower BMI. Only 34% met national PA
      guidelines; this proportion was significantly lower among blacks (OR 0.5, CI 0.3
      0.9). CONCLUSIONS: These overweight and obese postpartum women reported a large
      percentage of time spent in sedentary/light activity, and a high proportion
      failed to meet minimal guidelines for PA. Promotion of PA in the postpartum
      period should focus on reducing sedentary behaviors and increasing moderate PA.

PMID- 21885891
TI  - Ambulatory activity associations with cardiovascular and metabolic risk factors
      in smokers.
AB  - BACKGROUND: We examined the association between ambulatory activity and
      biological markers of health in smokers. METHODS: Baseline data from 985 subjects
      enrolled in a pharmacologic smoking cessation trial were examined. Body size,
      blood pressure, total cholesterol (TC), low density lipoprotein cholesterol (LDL
      C), total and small LDL particles, LDL size, high density lipoprotein
      cholesterol, triglycerides (TG), C-reactive protein (CRP), creatinine, fasting
      glucose, and hemoglobin A1c were assessed in relation to pedometer-assessed
      ambulatory activity, as was the odds of metabolic syndrome and CRP > 3 mg/L.
      Effect modification by gender was examined. RESULTS: Only waist circumference was
      lower with greater steps/day in the men and women combined (P(trend) < 0.001). No
      other significant relationships were noted in men, while women with >= 7500
      steps/day had lower weight, BMI, CRP, TG, total, and small LDL particles compared
      with those with < 7500 steps/day. These women also had 62% and 43% lower odds of
      metabolic syndrome and elevated CRP, respectively, compared with the less active
      women. Adjustment for BMI attenuated all the associations seen in women.
      CONCLUSIONS: Greater ambulatory activity is associated with lower levels of
      metabolic and cardiovascular risk factors in female smokers which may, in part,
      be mediated by a reduction in BMI.

PMID- 21885892
TI  - Step counts and energy expenditure as estimated by pedometry during treadmill
      walking at different stride frequencies.
AB  - BACKGROUND: The purposes of this study were to determine the accuracy and
      reliability of step counts and energy expenditure as estimated by a pedometer
      during treadmill walking and to clarify the relationship between step counts and
      current physical activity recommendations. METHODS: One hundred males (n = 50)
      and females (n = 50) walked at stride frequencies (SF) of 80, 90, 100, 110, and
      120 steps/min, during which time step counts and energy expenditure were
      estimated with a Walk4Life Elite pedometer. RESULTS: The pedometer accurately
      measured step counts at SFs of 100, 110, and 120 steps/min, but not 80 and 90
      steps/min. Compared with energy expenditure as measured by a metabolic cart, the
      pedometer significantly underestimated energy expenditure at 80 steps/min and
      significantly overestimated measured energy expenditure at 90, 100, 110, and 120
      steps/min. CONCLUSIONS: The pedometers' inability to accurately estimate energy
      expenditure cannot be attributed to stride length entered into the pedometer or
      its ability to measure step counts. Males met 3 criteria and females met 2
      criteria for moderate-intensity physical activity at SF of 110 to 120 steps/min.
      These results provide the basis for defining moderate-intensity physical activity
      based on energy expenditure and step counts and may lead to an appropriate
      steps/day recommendation.

PMID- 21885893
TI  - Validity and reliability of the Omron HJ-303 tri-axial accelerometer-based
      pedometer.
AB  - BACKGROUND: This study compared the validity of a new Omron HJ-303 piezoelectric
      pedometer and 2 other pedometers (Sportline Traq and Yamax SW200). METHODS: To
      examine the effect of speed, 60 subjects walked on a treadmill at 2, 3, and 4
      mph. Twenty subjects also ran at 6, 7, and 8 mph. To test lifestyle activities,
      60 subjects performed front-back-side-side stepping, elliptical machine and stair
      climbing/descending. Twenty others performed ballroom dancing. Sixty participants
      completed 5 100-step trials while wearing 5 different sets of the devices tested
      device reliability. Actual steps were determined using a hand tally counter.
      RESULTS: Significant differences existed among pedometers (P < .05). For walking,
      the Omron pedometers were the most valid. The Sportline overestimated and the
      Yamax underestimated steps (P < .05). Worn on the waist or in the backpack, the
      Omron device and Sportline were valid for running. The Omron was valid for 3
      activities (elliptical machine, ascending and descending stairs). The Sportline
      overestimated all of these activities, and Yamax was only valid for descending
      stairs. The Omron andYamax were both valid and reliable in the 100-step trials.
      CONCLUSIONS: The Omron HJ-303, worn on the waist, appeared to be the most valid
      of the 3 pedometers.

PMID- 21885894
TI  - Guest editor's introduction: Special section on the IEEE Pacific Visualization
      Symposium.

PMID- 21885895
TI  - Streamline integration using MPI-hybrid parallelism on a large multicore
      architecture.
AB  - Streamline computation in a very large vector field data set represents a
      significant challenge due to the nonlocal and data-dependent nature of streamline
      integration. In this paper, we conduct a study of the performance characteristics
      of hybrid parallel programming and execution as applied to streamline integration
      on a large, multicore platform. With multicore processors now prevalent in
      clusters and supercomputers, there is a need to understand the impact of these
      hybrid systems in order to make the best implementation choice. We use two MPI
      based distribution approaches based on established parallelization paradigms,
      parallelize over seeds and parallelize over blocks, and present a novel MPI
      hybrid algorithm for each approach to compute streamlines. Our findings indicate
      that the work sharing between cores in the proposed MPI-hybrid parallel
      implementation results in much improved performance and consumes less
      communication and I/O bandwidth than a traditional, nonhybrid distributed
      implementation.

PMID- 21885896
TI  - Bone structure and density via HR-pQCT in 60d bed-rest, 2-years recovery with and
      without countermeasures.
AB  - We examined the effects of bed-rest, recovery and exercise countermeasures on
      bone density and structure at the distal tibia and radius as measured via high
      resolution peripheral computed tomography. 24 subjects underwent 60-days of head
      down tilt bed-rest and performed either resistive vibration exercise (RVE; n =
      7), resistive exercise only (RE; n = 8) or no exercise (n = 9; 2nd Berlin BedRest
      Study; BBR2-2). Measurements were performed regularly during and up to 2-years
      after 60d bed-rest. At the distal tibia marked reductions in cortical area,
      cortical thickness and bone density but increases in periosteal perimeter and
      trabecular area were seen (p all<0.001). Recovery of most parameters occurred
      within 180d after bed-rest. At the distal radius, persistent increases in
      cortical area, cortical thickness, cortical density and total density and
      decreases in trabecular area were seen (p all <= 0.005). A significant effect of
      RVE (p = 0.003), but not RE, was seen on cortical area at the distal tibia, with
      few effects of the countermeasures observed on the remaining parameters. The
      current study represents the first implementation of high-resolution peripheral
      computed tomography in bed-rest in male subjects and helps to understand the
      patterns of bone remodeling due to bed-rest and recovery.

PMID- 21885897
TI  - Skeletal differences at the ulna and radius between pre-pubertal non-elite female
      gymnasts and non-gymnasts.
AB  - OBJECTIVE: To compare skeletal parameters between the ulna and radius in pre
      pubertal non-elite gymnasts and non-gymnasts. METHODS: Fifty-eight non-elite
      artistic gymnasts, aged 6-11 years, were compared with 28 non-gymnasts for bone
      mineral content (BMC), total and cortical bone area (ToA, CoA), trabecular and
      cortical volumetric density (TrD, CoD) and estimated bone strength (BSI and
      SSIp), obtained by pQCT at the distal and proximal forearm. RESULTS: Gymnasts had
      greater estimated bone strength than non-gymnasts at both sites of the forearm.
      At the distal forearm, the gymnastics-induced skeletal benefits were greater at
      the radius than ulna (Z-scores for BMC, TrD and BSI +0.40 to +0.61 SD, p<0.05 vs.
      +0.15 to +0.48 SD, NS). At the proximal forearm, the skeletal benefits were
      greater at the ulna than the radius (Z-scores for BMC, ToA, CoA and SSIp +0.59 to
      +0.82 SD, p<0.01 vs. +0.35 (ToA) and +0.43 SD (SSIp), p<0.01). CONCLUSION:
      Skeletal benefits at the distal and proximal forearm emerged in young non-elite
      gymnasts. Benefits were larger when considering skeletal parameters at both the
      ulna and radius, than the radius alone as traditionally performed with pQCT.
      These findings suggest the ulna is worth investigating in future studies aiming
      to accurately quantify exercise-induced skeletal adaptations.

PMID- 21885899
TI  - An open source approach for regional cortical bone mineral density analysis.
AB  - OBJECTIVE: Cortical porosity, particularly at the endocortical region, is
      recognised to play a central role in the pathogenesis of bone fragility.
      Therefore, the purpose of this study was to: 1) demonstrate how cortical
      volumetric BMD (vBMD) distribution can be analysed from (p)QCT images and 2)
      highlight the clinical significance of assessing regional density distribution of
      cortical bone. METHODS: We used pQCT to compare mid-tibial cortical volumetric
      BMD distribution of 20 young (age 24(SD2) years, mass 77(11) kg, height 178(6)
      cm) and 25 elderly (72(4) years, 75(9) kg, 172(5) cm) men. Radial and polar
      cortical vBMD distributions were analysed using a custom built open source
      analysis tool which allowed the cortex to be divided into three concentric
      cortical divisions and in 36 cortical sectors originating from the centroid of
      the bone. RESULTS: Mean vBMD did not differ between the groups (1135(16) vs.
      1130(28) mg/cm, P = 0.696). In contrast, there was a significant age-group by
      radial division interaction for radial cortical vBMD (P<0.001). CONCLUSIONS: The
      proposed analysis method for analysing cortical bone density distribution of pQCT
      images was effective for detecting regional differences in cortical density
      between young and elderly men, which would have been missed by just looking at
      mean vBMD values.

PMID- 21885898
TI  - Mechanical-tactile stimulation (MTS) intervention in a neonatal stress model
      improves long-term outcomes on bone.
AB  - OBJECTIVES: Neonatal stress impairs postnatal bone mineralization. Evidence
      suggests that mechanical tactile stimulation (MTS) in early life decreases stress
      hormones and improves bone mineralization. Insulin-like growth factor (IGF1) is
      impacted by stress and essential to bone development. We hypothesized that MTS
      administered during neonatal stress would improve bone phenotype in later life.
      We also predicted an increase in bone specific mRNA expression of IGF1 related
      pathways. METHODS: Neonatal stress (STRESS) and MTS (STRESS+10 min of MTS) were
      given from D6 to D10 of rat life and tissue was harvested on D60 of life. Dual
      energy x-ray absorptiometry (DXA), bone morphometry, serum osteocalcin, type I
      procollagen N-terminal propeptide (PINP), tartrate-resistant acid phosphatase
      (TRAP), and bone and liver mRNA levels of IGF1, IGF1 receptor (IGF1R), and growth
      hormone receptor (GHR) were measured. RESULTS: Stress resulted in reduced bone
      area and bone mineral content (BMC) compared to naive control (CTL). MTS
      intervention increased BMC and tibial growth plate width compared to STRESS. MTS
      also resulted in higher osteocalcin, and, in males, lower TRAP (p<0.05). MTS
      resulted in three-fold, two-fold, and six-fold higher bone specific IGF1, IGF1R,
      and GHR, respectively (p <= 0.001) compared to STRESS. CONCLUSIONS: MTS in early
      postnatal life improves long-term bone mineralization. IGF1 and related pathways
      may explain improved BMC.

PMID- 21885900
TI  - The accuracy of clinical kyphosis examination for detection of thoracic vertebral
      fractures: comparison of direct and indirect kyphosis measures.
AB  - OBJECTIVE: To compare the accuracies of two simple physical examination maneuvers
      for detecting the presence of thoracic vertebral fractures (VF) diagnosed by
      radiography: direct measurement of kyphosis angle (KA, in degrees) and indirect
      measurement using wall-occiput distance (WOD, in cm). METHODS: Subjects were 280
      women (average age, 54.5 years; range, 18-92) referred for assessment of
      osteoporosis. KA was measured from T4 to T12 using a digital inclinometer while
      WOD was measured with the patient in a standardized position. VF were diagnosed
      on radiographs using semi-quantitative morphometry. RESULTS: KA and WOD were
      moderately correlated (r = 0.72, p<10(-11)). KA increased by 3.7(o) (95% CI, 2.6
      4.8(o)) for each VF (p = 4x 10(-11)) and WOD rose 1.3 cm (95% CI, 0.8-1.7 cm) per
      VF (p = 2 x 10(-11)). The areas under the receiver operating characteristic
      curves were 0.72 (95% CI, 0.65-0.79) for KA and 0.76 (95% CI, 0.69-0.82) for WOD,
      which were not significantly different (p = 0.13). CONCLUSIONS: Given similar
      performances of direct and indirect measures of kyphosis, we propose that WOD
      should be used in clinical practice, with a clinical threshold of WOD>4.0 cm as
      an indication to consider spine radiography. At this WOD threshold, sensitivity
      was 41% (95% CI, 31-52%) and specificity was 92% (95% CI, 87-95%). WOD should be
      considered for use in the clinical assessment of osteoporosis patients.

PMID- 21885901
TI  - Spinal cord injury-related bone impairment and fractures: an update on
      epidemiology and physiopathological mechanisms.
AB  - A sudden loss of motor function in segments of the spinal cord results in
      immobilisation and is complicated by bone loss and fractures in areas below the
      level of injury. Despite the acceptance of osteoporosis and fractures as two
      major public health problems, in people with spinal cord injuries, the mechanisms
      are not adequately investigated. Multiple risk factors for bone loss and
      fractures are present in this disabled population. This review is an update on
      the epidemiology and physiopathological mechanisms in spinal cord injury-related
      bone impairment and fractures.

PMID- 21885902
TI  - Tertiary hyperparathyroidism in a patient with X-linked hypophosphatemic rickets.

PMID- 21885903
TI  - Pressure algometry: what does it really tell us?

PMID- 21885904
TI  - Thoracic spine thrust manipulation improves pain, range of motion, and self
      reported function in patients with mechanical neck pain: a systematic review.
AB  - STUDY DESIGN: Systematic review. BACKGROUND: Neck pain is a common diagnosis in
      the physical therapy setting, yet there is no gold standard for treatment. This
      study is part of a growing body of literature on the use of thoracic spine thrust
      manipulation for the treatment of individuals with mechanical neck pain.
      OBJECTIVE: The purpose of this systematic review was to determine the effects of
      thoracic spine thrust manipulation on pain, range of motion, and self-reported
      function in patients with mechanical neck pain. METHODS: Six online databases
      were comprehensively searched from their respective inception to October 2010.
      The primary search terms included "thoracic mobilization," "thoracic spine
      mobilization," "thoracic manipulation," and "thoracic spine manipulation." Of the
      44 studies assessed for inclusion, 6 randomized controlled trials were retained.
      Between-group mean differences and effect sizes for pretreatment-to-posttreatment
      change scores, using Cohen's d formula, were calculated for pain, range of
      motion, and subjective function at all stated time intervals. RESULTS: Effect
      size point estimates for the pain change scores were significant for global
      assessment across all studies (range, 0.38-4.03) but not conclusively significant
      at the end range of active rotation (range, 0.02-1.79). Effect size point
      estimates were large among all range-of-motion change measures (range, 1.40
      3.52), and the effect size point estimates of the change scores among the
      functional questionnaires (range, 0.47-3.64) also indicated a significant
      treatment effect. CONCLUSIONS: Thoracic spine thrust manipulation may provide
      short-term improvement in patients with acute or subacute mechanical neck pain.
      However, the body of literature is weak, and these results may not be
      generalizable. LEVEL OF EVIDENCE: Therapy, level 1b-.

PMID- 21885905
TI  - Neck pain: manipulating the upper back helps lessen pain and improve neck motion.
AB  - Neck pain is very common. In the United States, between 30% and 50% of people
      suffer from an aching neck each year. Although neck pain can be caused by injury,
      most of this pain results from more gradual stresses, such as particular sitting,
      standing, or work postures, lifting patterns, or sleeping positions. Typical neck
      pain can also cause headaches, pain between your shoulders, or a feeling of knots
      in your neck and upper back muscles. Although manual therapy, sometimes called
      "manipulation," is a common treatment for many types of spine pain, some people
      are uncomfortable having their necks manipulated. Recently, though, researchers
      have tested the benefits of a thrust manipulation of the upper back to treat neck
      pain. A study published in the September 2011 issue of JOSPT provides new insight
      and an evidence-based summary of the benefits of manipulating the upper back to
      ease and eliminate neck pain.

PMID- 21885906
TI  - Reliability, standard error, and minimum detectable change of clinical pressure
      pain threshold testing in people with and without acute neck pain.
AB  - STUDY DESIGN: Clinical measurement. OBJECTIVES: To evaluate the intrarater,
      interrater, and test-retest reliability of an accessible digital algometer, and
      to determine the minimum detectable change in normal healthy individuals and a
      clinical population with neck pain. BACKGROUND: Pressure pain threshold testing
      may be a valuable assessment and prognostic indicator for people with neck pain.
      To date, most of this research has been completed using algometers that are too
      resource intensive for routine clinical use. METHODS: Novice raters
      (physiotherapy students or clinical physiotherapists) were trained to perform
      algometry testing over 2 clinically relevant sites: the angle of the upper
      trapezius and the belly of the tibialis anterior. A convenience sample of normal
      healthy individuals and a clinical sample of people with neck pain were tested by
      2 different raters (all participants) and on 2 different days (healthy
      participants only). Intraclass correlation coefficient (ICC), standard error of
      measurement, and minimum detectable change were calculated. RESULTS: A total of
      60 healthy volunteers and 40 people with neck pain were recruited. Intrarater
      reliability was almost perfect (ICC = 0.94-0.97), interrater reliability was
      substantial to near perfect (ICC = 0.79-0.90), and test-retest reliability was
      substantial (ICC = 0.76-0.79). Smaller change was detectable in the trapezius
      compared to the tibialis anterior. CONCLUSIONS: This study provides evidence that
      novice raters can perform digital algometry with adequate reliability for
      research and clinical use in people with and without neck pain.

PMID- 21885907
TI  - A descriptive study of pressure pain threshold at 2 standardized sites in people
      with acute or subacute neck pain.
AB  - STUDY DESIGN: Cross-sectional convenience sample. OBJECTIVES: To describe the
      distribution of scores for pressure pain threshold (PPT) at 2 standardized
      testing sites in people with neck pain of less than 90 days' duration: the angle
      of the upper trapezius and the belly of the tibialis anterior. A secondary
      objective was to identify important influences on PPT. BACKGROUND: PPT may be a
      valuable assessment and prognostic indicator for people with neck pain. However,
      to facilitate interpretation of scores, knowledge of means and variance for the
      target population, as well as factors that might influence scores, is needed.
      METHODS: Participants were recruited from community-based physiotherapy clinics
      and underwent PPT testing using a digital algometer and standardized protocol.
      Descriptive statistics (mean, standard deviations, quartiles, skewness, and
      kurtosis) were calculated for the 2 sites. Simple bivariate tests of association
      were conducted to explore potential moderators. RESULTS: A positively skewed
      distribution was described for the 2 standardized sites. Significant moderators
      were sex (male higher than female), age (r = 0.22), and self-reported pain
      intensity (r = -0.24). Neither litigation status nor most symptomatic/least
      symptomatic side influenced PPT. CONCLUSIONS: This manuscript presents
      information regarding the expected scores for PPT testing in people with acute or
      subacute neck pain. Clinicians can compare the results of individual patients
      against these population values, and researchers can incorporate the significant
      confounders of age, sex, and self-reported pain intensity into future research
      designs.

PMID- 21885908
TI  - Pressure pain threshold testing demonstrates predictive ability in people with
      acute whiplash.
AB  - STUDY DESIGN: Longitudinal cohort study. OBJECTIVES: To determine whether
      pressure pain threshold (PPT), tested at 2 standardized sites, could provide
      additional prognostic ability to predict short-term outcomes in people with acute
      whiplash, after controlling for age, sex, and baseline pain intensity.
      BACKGROUND: PPT may be a valuable assessment and prognostic indicator for people
      with whiplash-associated disorder. The extent to which PPT can predict short-term
      disability scores has yet to be explored in people with acute (of less than 30
      days in duration) whiplash-associated disorder in a clinical setting. METHODS:
      Eligible patients were recruited from community-based physiotherapy clinics in
      Canada. Baseline measurements included PPT, as well as pain intensity, age, and
      sex. Neck-related disability was collected with the Neck Disability Index 1 to 3
      months after PPT testing. Multiple linear regression models were constructed to
      evaluate the unique contribution of PPT in the prediction of follow-up disability
      scores. RESULTS: A total of 45 subjects provided complete data. A regression
      model that included sex, baseline pain intensity, and PPT at the distal tibialis
      anterior site was the most parsimonious model for predicting short-term Neck
      Disability Index scores 1 to 3 months after PPT testing, explaining 38.6% of the
      variance in outcome. None of the other variables significantly improved the
      predictive power of the model. CONCLUSION: Sex, pain intensity, and PPT measured
      at a site distal to the injury were the most parsimonious set of predictors of
      short-term neck-related disability score, and represented promising additions to
      assessment of traumatic neck pain. Neither age nor PPT at the local site was able
      to explain significant variance beyond those 3 predictors. Limitations to
      interpretation are addressed.

PMID- 21885909
TI  - Criteria-based management of an acute multistructure knee injury in a
      professional football player: a case report.
AB  - STUDY DESIGN: Case report. BACKGROUND: Joint stiffness, also called
      arthrofibrosis, remains the primary complication following any reconstructive
      knee surgery. Acute anterior cruciate ligament surgery, performed with
      concomitant multiple ligamentous repair and/or reconstruction, further increases
      the likelihood of developing impaired knee motion following surgery. The purpose
      of this case report is to present a criteria-based approach to the postoperative
      management of a multiligament knee injury. CASE DESCRIPTION: A 25-year-old male
      professional football player sustained a contact injury to his right knee while
      making a tackle during a regular season game in 2007. He underwent an acute
      anterior cruciate ligament reconstruction, with concomitant posterolateral corner
      repair, biceps femoris/iliotibial band repair, lateral collateral ligament
      repair, and a medial meniscocapsular junction repair. He completed 17 weeks of a
      multiphased rehabilitation program that emphasized immediate range of motion, low
      load long-duration stretching, therapeutic exercise, neuromuscular
      reeducation/perturbation training, plyometrics, and sport-specific functional
      drills. Electrical neurostimulation was implemented during the early stages of
      rehabilitation to control postoperative pain and to promote a steady progression
      of therapeutic exercise activity. OUTCOMES: The patient was cleared to begin
      sport-specific activity 7 months after major multistructure reconstructive knee
      surgery. He began the 2008 season on the physically-unable-to-perform list, but
      was activated midseason and played in every game thereafter. During the 2009 and
      2010 seasons, he played all regular season games and all playoff games as a
      starter, and continues to start as a defensive cornerback in the National
      Football League. DISCUSSION: This case report highlights the clinical decision
      making process and management involved in an acute multiple ligamentous knee
      injury/reconstruction. LEVEL OF EVIDENCE: Therapy, level 4.

PMID- 21885910
TI  - Women with posterior tibial tendon dysfunction have diminished ankle and hip
      muscle performance.
AB  - STUDY DESIGN: Controlled laboratory study using a cross-sectional design.
      OBJECTIVES: To characterize ankle and hip muscle performance in women with
      posterior tibial tendon dysfunction (PTTD) and compare them to matched controls.
      We hypothesized that ankle plantar flexor strength, and hip extensor and abductor
      strength and endurance, would be diminished in women with PTTD and this
      impairment would be on the side of dysfunction. BACKGROUND: Individuals with PTTD
      demonstrate impaired walking abilities. Walking gait is strongly dependent on the
      performance of calf and hip musculature. METHODS: Thirty-four middle-aged women
      (17 with PTTD) participated. Ankle plantar flexor strength was assessed with the
      single-leg heel raise test. Hip muscle performance, including strength and
      endurance, were dynamometrically measured. Differences between groups and sides
      were assessed with a mixed-model analysis of variance. RESULTS: Females with PTTD
      performed significantly fewer single-leg heel raises and repeated sagittal and
      frontal plane non-weight-bearing leg lifts, and also had lower hip extensor and
      abductor torques than age-matched controls. There were no differences between
      sides for hip strength and endurance measures for either group, but differences
      between sides in ankle strength measures were noted in both groups. CONCLUSION:
      Women with PTTD demonstrated decreased ankle and hip muscle performance
      bilaterally.

PMID- 21885911
TI  - Proximal tibial fracture following total knee arthroplasty.
AB  - The patient was a 74-year-old man, with a history of total knee arthoplasty 14
      years earlier, after having sustained a pathological fracture of the proximal
      diaphysis of the left tibia following a fall. Given the unstable nature of the
      fracture and the severe osteolysis noted below the total knee arthroplasty,
      surgical management 1 day after the fall entailed packing cancellous bone graft
      into the defect and realigning the fracture.

PMID- 21885912
TI  - Metallic foreign body in a patient with knee pain.
AB  - The patient was a 26-year-old man with a history of a nonhealing, complicated
      right clavicle fracture. He also complained of right medial knee pain that was
      thought to be insidious in onset and made worse during magnetic resonance
      imaging, which was done to evaluate the status of the right clavicle fracture.
      Subsequent to the patient reporting his right knee pain to his orthopaedic
      surgeon, magnetic resonance imaging of the right knee was ordered. Anterior-to
      posterior and lateral radiographs were then ordered by the physical therapist,
      which identified a radioopaque foreign body along the medial knee within the
      subcutaneous tissues.

PMID- 21885915
TI  - Antibody microarray analysis of the serum proteome in primary breast cancer
      patients.
AB  - Noninvasive biomarkers are urgently needed for detecting breast cancer as early
      as possible since the risk of recurrence, morbidity, and mortality is closely
      related to disease stage at the time of primary surgery. There are currently no
      such biomarkers in clinical use as a diagnostic tool. Proteomic analysis of
      protein expression patterns in body fluids has potential for use in identifying
      biomarkers of breast cancer. The aim of this study was to compare protein
      expression levels in the sera of primary breast cancer patients and healthy
      controls. An antibody microarray tool with 23 antibodies immobilized on
      nitrocellulose slides was used to determine the levels of acute phase proteins,
      interleukins, and complement factors in the sera of 101 study participants (49
      women with primary breast cancer and 52 healthy age-matched controls).
      Statistical analysis of reaction intensities identified 6 proteins that showed
      significantly (p < 0.05) different levels in breast cancer patients vs. healthy
      subjects. The neural network distinguished cancer patients from controls with a
      sensitivity of 69% and a specificity of 76%. Thus, antibody microarray analysis
      could be used as a tool for the development of improved diagnostics and biomarker
      discovery for breast cancer patients. Further validation of the results and de
      novo screening of new biomarkers could facilitate the early diagnosis of breast
      cancer.

PMID- 21885917
TI  - HO-3867, a curcumin analog, sensitizes cisplatin-resistant ovarian carcinoma,
      leading to therapeutic synergy through STAT3 inhibition.
AB  - Cisplatin resistance is a major obstacle in the treatment of ovarian cancer. Drug
      combinations with synergistic or complementary functions are a promising strategy
      to overcome this issue. We studied the anticancer efficacy of a novel compound,
      HO-3867, used in combination with cisplatin against chemotherapy-resistant
      ovarian cancer. A2780R cells, a cisplatin-resistant human ovarian cancer cell
      line, were exposed to 1, 5, or 10 uM of HO-3867 alone or in combination with
      cisplatin (10 ug/ml) for 24 hours. Cell viability (MTT), proliferation (BrdU),
      cell-cycle analysis (FACS), and protein expression (western blot) were used for
      in vitro studies. STAT3 overexpression was performed using transfected STAT3
      cDNA. In vivo studies used cisplatin-resistant xenograft tumors grown in nude
      mice and treated with 100-ppm HO-3867 and weekly injections of 4-mg/kg cisplatin.
      HO-3867/cisplatin combination treatment significantly inhibited cisplatin
      resistant cell proliferation in a concentration-dependent manner. The inhibition
      was associated with increased expression of p53 and p21, and decreased expression
      of cdk5 and cyclin D1. Apoptosis was induced by activation of Bax, cytochrome c
      release, and stimulated cleavage of caspase-9, caspase-3, and PARP.
      Overexpression of STAT3 decreased the HO-3867-induced apoptosis. The combination
      treatment significantly inhibited the growth of cisplatin-resistant xenograft
      tumors with significant downregulation of pSTAT3, and without apparent toxicity
      to healthy tissues. The combination treatment exhibited synergistic anticancer
      efficacy, which appears largely due to HO-3867-induced downregulation of pSTAT3.
      The results, combined with the previously-reported safety features of HO-3867,
      suggest the potential use of this compound as a safe and effective adjuvant for
      the treatment of ovarian cancer.

PMID- 21885916
TI  - VMY-1-103 is a novel CDK inhibitor that disrupts chromosome organization and
      delays metaphase progression in medulloblastoma cells.
AB  - Medulloblastoma is the most prevalent of childhood brain malignancies,
      constituting 25% of childhood brain tumors. Craniospinal radiotherapy is a
      standard of care, followed by a 12mo regimen of multi-agent chemotherapy. For
      children less than 3 y of age, irradiation is avoided due to its destructive
      effects on the developing nervous system. Long-term prognosis is worst for these
      youngest children and more effective treatment strategies with a better
      therapeutic index are needed. VMY-1-103, a novel dansylated analog of purvalanol
      B, was previously shown to inhibit cell cycle progression and proliferation in
      prostate and breast cancer cells more effectively than purvalanol B. In the
      current study, we have identified new mechanisms of action by which VMY-1-103
      affected cellular proliferation in medulloblastoma cells. VMY-1-103, but not
      purvalanol B, significantly decreased the proportion of cells in S phase and
      increased the proportion of cells in G(2)/M. VMY-1-103 increased the sub G(1)
      fraction of apoptotic cells, induced PARP and caspase-3 cleavage and increased
      the levels of the Death Receptors DR4 and DR5, Bax and Bad while decreasing the
      number of viable cells, all supporting apoptosis as a mechanism of cell death.
      p21(CIP1/WAF1) levels were greatly suppressed. Importantly, we found that while
      both VMY and flavopiridol inhibited intracellular CDK1 catalytic activity, VMY-1
      103 was unique in its ability to severely disrupt the mitotic spindle apparatus
      significantly delaying metaphase and disrupting mitosis. Our data suggest that
      VMY-1-103 possesses unique antiproliferative capabilities and that this compound
      may form the basis of a new candidate drug to treat medulloblastoma.

PMID- 21885919
TI  - Recent advances in post-kala-azar dermal leishmaniasis.
AB  - PURPOSE OF REVIEW: Post-kala-azar dermal leishmaniasis (PKDL) is a challenge for
      clinicians and researchers, because its burden is poorly investigated and
      pathogenesis is disputable. However, recent studies contributed to understanding
      of the pathogenesis of PKDL especially its association with host immunological
      factors, and also how to improve its diagnosis and treatment. This review focuses
      on recent advances in diagnosis, new insights into pathogenesis and case
      management. RECENT FINDINGS: Information regarding the burden of PKDL, especially
      in Bangladesh, is now available. Association between skin parasite burden and
      different clinical forms of PKDL has been explored. The diagnostic importance of
      detection of Leishmania donovani DNA in the peripheral blood buffy coat and in
      skin specimens by PCR has been studied. Variable effects of different
      antileishmanial drugs on immune response have been observed. Finally, high
      efficacy of miltefosine for treatment of PKDL has been demonstrated. SUMMARY: The
      incidence of PKDL is reducing in India after introduction of miltefosine and
      amphotericin B for treatment of visceral leishmaniasis. It remains higher in
      Bangladesh and in Sudan. Parasite burden is higher in nodular and papular forms
      of PKDL compared to the macular form of the disease. The demonstration of
      Leishmania DNA in peripheral blood buffy coat and in skin specimens can help to
      diagnose 40-75% clinically suspected PKDL individuals. An initial cure rate of
      95% has been achieved with miltefosine for treatment of PKDL. However, the
      efficacy of combination therapy should be explored to reduce the treatment
      duration and hence to improve treatment compliance.

PMID- 21885921
TI  - Current world literature.

PMID- 21885920
TI  - The company malaria keeps: how co-infection with Epstein-Barr virus leads to
      endemic Burkitt lymphoma.
AB  - PURPOSE OF REVIEW: Co-infection with Plasmodium falciparum malaria and Epstein
      Barr virus (EBV) are implicated in the cause of endemic Burkitt lymphoma (eBL),
      the most prevalent pediatric cancer in equatorial Africa. Although the causal
      association between EBV and eBL has been established, P. falciparum malaria's
      role is not as clearly defined. This review focuses on how malaria may disrupt
      EBV persistence and immunity. RECENT FINDINGS: Two mutually compatible theories
      have been proposed. One suggests that P. falciparum malaria induces polyclonal B
      cell expansion and lytic EBV reactivation, leading to the expansion of latently
      infected B cells and the likelihood of a c-myc translocation, a hallmark of
      Burkitt lymphoma tumors. The other advocates that EBV-specific T-cell immunity is
      impaired during P. falciparum malaria co-infection, either as a cause or
      consequence of enhanced EBV replication, leading to loss of viral control.
      Advancements in our ability to query the complexity of human responses to
      infectious diseases have stimulated interest in eBL pathogenesis. SUMMARY: EBV is
      necessary but not sufficient to cause eBL. A more dynamic model encompasses
      incremental contributions from both chronic and acute P. falciparum malaria
      leading to alterations in EBV persistence and EBV-specific immunity that
      culminate in eBL. A better understanding of how P. falciparum malaria modifies
      EBV infections in children may allow us to anticipate reductions in eBL incidence
      coinciding with malaria control programs.

PMID- 21885922
TI  - A counselee-oriented perspective on risk communication in genetic counseling:
      explaining the inaccuracy of the counselees' risk perception shortly after
      BRCA1/2 test result disclosure.
AB  - PURPOSE: Genetic counseling may help counselees understand their genetic risk of
      developing breast/ovarian cancer. However, many studies have shown that their
      perception of their risks is inaccurate. Information-oriented variables often
      predicted the level of accuracy, focusing on specific processes of receiving and
      processing risks. We examined counselee-oriented predictors about how counselees
      embed cancer risks in their lives. These predictors reflect the personal meaning
      of genetic risks and are expected to explain/mediate the impact of genetic
      counseling on risk-perception-accuracy. METHOD: We analyzed 248 questionnaires of
      a prospective study, filled in by probands with breast/ovarian cancer and
      pathogenic mutations, unclassified variants, or uninformative results (n = 30,
      16, and 202, respectively). Mediation regression analyses were performed to
      examine whether counselee predictors mediated/explained the influence of
      information predictors on the accuracy. Information-oriented predictors regarded
      presentation format, communicated information, question format, education,
      pedigree information, cancer experience, and cognitive processes/heuristics.
      Counselee-oriented predictors regarded their self/personality, life/existence,
      and need for certainty about DNA test result, heredity, and cancer. RESULTS: Both
      information-oriented and counselee-oriented variables significantly predicted the
      accuracy of the counselees' risk perception, with moderate to large effect sizes.
      Counselee-oriented variables completely mediated/explained the effects of
      information-oriented variables on the accuracy. DISCUSSION: Counselees seemed to
      transform objective cancer risks into personally relevant information. Only
      through this personal meaning of genetic information, information-oriented
      processes seemed to cause inaccurate perceptions. Genetic counselors are
      suggested to focus communication on these personal processes.

PMID- 21885923
TI  - Informed consent and immunohistochemistry screening for Lynch syndrome.

PMID- 21885925
TI  - Folic acid and neural tube defects.

PMID- 21885926
TI  - Basic science for the clinician 51: the inflammasome.
AB  - The innate immune system is packaged in a number of discrete, but
      intercommunicating, systems. The inflammasome is a multimolecular complex that
      detects intracellular foreign molecules of a variety of sorts and promptly
      promotes the secretion of IL-1beta and IL-18. When all goes well, defense of the
      organism in the early period of infection is enhanced by this system; when
      certain elements of the inflammasomal systems go awry, inflammatory diseases of a
      variety of sorts result. A family of multimolecular detection systems are
      activated at times of infection and tissue damage; it is the dysfunction of this
      innate immune defense system that intrigues rheumatologists, as this is the cause
      of a series of newly described autoinflammatory diseases.

PMID- 21885927
TI  - Lupus pernio: sarcoid-specific cutaneous manifestation associated with chronic
      sarcoid arthropathy.

PMID- 21885928
TI  - Crystal deposition at elbow hyaline cartilage: the sonographic perspective.

PMID- 21885929
TI  - Destructive tophaceous gout: imaging characteristics.

PMID- 21885931
TI  - Spinal epidural abscess on rituximab.

PMID- 21885932
TI  - Tdap vaccination strategies for health care personnel.

PMID- 21885933
TI  - Encouraging patients and families to influence change on a palliative care unit:
      value of patient satisfaction surveys.
AB  - This article describes how a series of patient satisfaction surveys on a
      palliative care unit were used to help influence the care provided to patients
      and their families. Innovative interventions aimed at addressing areas of lower
      satisfaction identified in the initial survey are described. The results from a
      follow-up survey provided the opportunity to evaluate whether our interventions
      were effective in improving patient satisfaction and highlight new areas of
      concern needing to be addressed.

PMID- 21885935
TI  - Omega 3 fatty acid supplements and cardiovascular health: commentary on the
      article by de Jong et al. on page 411.

PMID- 21885936
TI  - IUGR in the absence of postnatal "catch-up" growth leads to improved whole body
      insulin sensitivity in rat offspring.
AB  - A suboptimal in utero environment leads to fetal adaptations to ensure short-term
      survival but in the long-term may lead to disease when the postnatal growth does
      not reflect that in utero. This study examined the effect of IUGR on whole body
      insulin sensitivity and metabolic activity in adult rats. Female Wistar-Kyoto
      rats were fed either a normal protein diet (NPD 20% casein) or a low protein diet
      (LPD; 8.7% casein) during pregnancy and 2 wk of lactation. In offspring at 32 wk
      of age, indirect calorimetry and dual energy x-ray absorptiometry (DEXA) were
      performed to assess metabolic activity and body composition. Insulin sensitivity
      was assessed using a euglycemic-hyperinsulinemic clamp. At 3 d of age, male and
      female LPD offspring were 23 and 27% smaller than controls, respectively. They
      remained significantly smaller throughout the experimental period (~10% smaller
      at 32 wk). Importantly, there was increased insulin sensitivity in LPD offspring
      (47% increase in males and 38% increase in females); pancreatic insulin content
      was normal. Body composition, O2 consumption, respiratory exchange ratio (RER),
      and locomotor activity were not different to controls. These findings suggest
      that in the absence of "catch-up" growth IUGR programs for improved insulin
      sensitivity.

PMID- 21885937
TI  - Letter to the editor Re: Okogbule-Wonodi et al. Pediatr Res 69:442-447.

PMID- 21885938
TI  - Letter to the editor Re: Singh AJ et al. Pediatr Res 67:619-623.

PMID- 21885940
TI  - MART-1 is a reliable melanocytic marker in lichen planus-like keratosis: a study
      on 70 cases.
AB  - Recent studies have proposed that MART-1 may falsely stain clusters of
      intraepidermal nonmelanocytic cells in lichenoid dermatitides. This may become an
      issue especially in isolated lesions of lichen planus-like keratosis (LPLK), a
      condition also known as benign lichenoid keratosis, and one that is often
      mistaken clinically for a malignant cutaneous neoplasm. LPLKs are known to
      exhibit basal epidermal pseudonests, mimicking a regressing melanocytic lesion
      histologically, and often may prompt the pathologist to obtain a MART-1 stain. If
      MART-1 is falsely positive, it may seal an incorrect diagnosis. To determine
      whether or not pseudonests in LPLK decorated with MART-1, we reviewed 70 cases
      from our institution, stained them with MART-1 (Thermo Fisher-Lab Vision, Ab3
      clone, 1:400 dilution, heat-induced epitope retrieval with 0.02M citrate buffer
      at pH 6.0), and evaluated them for the presence or absence of staining within
      pseudonests. Four cases demonstrated an occasional MART-1-positive junctional
      nest. In these cases, microphthalmia transcription factor was also positive,
      confirming a true melanocytic origin. None of the other cases showed a MART-1
      pattern that would have been suspicious for a melanocytic lesion. We propose that
      this discrepancy between our study and prior ones may be explained by differences
      in staining protocols or by a very low incidence of non-specific staining. Our
      study suggests that MART-1 is a useful marker in differentiating melanocytic
      nests from pseudonests in LPLK.

PMID- 21885941
TI  - An infrequent case of neoplasm with fibroepithelioma of pinkus and
      hidradenomatous features arising at the umbilicus: a rare finding.

PMID- 21885942
TI  - Basal cell carcinoma with myoepithelial differentiation.
AB  - A lesion from the left cheek of a 48-year-old man showed a neoplasm composed
      primarily of cells with eccentric crescent-shaped nuclei and abundant,
      homogenous, eosinophilic cytoplasm resembling signet ring cells.
      Immunohistochemical studies showed the cells to stain positively for pan
      cytokeratin and smooth muscle actin, indicating myoepithelial differentiation
      (MED). Foci of conventional basal cell carcinoma were present, and cells with MED
      were also admixed within some of the aggregations of basal cell carcinoma. On the
      basis of these findings, we interpreted this lesion to represent basal cell
      carcinoma with MED. A review of the existing literature of basal cell carcinomas
      with similar morphologic features is also presented.

PMID- 21885943
TI  - Cutaneous metastasis of medullary thyroid carcinoma as the initial manifestation
      of an otherwise limited malignancy: a case report.
AB  - Cutaneous metastasis from a thyroid carcinoma, particularly medullary thyroid
      carcinoma (MTC), are rare. Herein, we report the first case of MTC in which
      metastatic lesions, were also the earliest sign of the disease, affecting the
      skin. This is as well the third reported case of undetected MTC initially
      manifested by metastatic skin lesions. A 79-year-old white woman presented with
      painful skin lesions. The lesions were biopsied. Based on routine light
      microscopic examination and immunohistochemical study, MTC was the most likely
      diagnosis. Subsequent investigations identified the primary thyroid tumor, which
      also proved to be MTC. No other metastatic lesion could be demonstrated by
      further evaluations. This report illustrates a novel presentation of MTC. MTC
      metastases should be considered in the differential diagnosis of cutaneous
      lesions. It is important to histopathologically examine the lesions and perform
      appropriate immunohistochemical study that must include calcitonin and other
      neuroendocrine markers.

PMID- 21885944
TI  - Cutaneous mucinous carcinoma arising in extramammary Paget disease of the
      perineum.
AB  - We present the case of a 74-year-old woman with a 7-year history of an expanding
      vulval and perianal erythematous plaque, which failed to respond to topical
      treatments in the community. Biopsy of the affected skin showed typical features
      of extramammary Paget disease. No underlying associated malignancy was
      identified. After 2 months of treatment with 5% topical imiquimod, the patient
      developed a new tender nodule in the perineal region. Histological examination
      revealed a mucinous carcinoma, which, after careful clinical assessment, was
      deemed to be a primary cutaneous mucinous carcinoma. This is the second reported
      case of a primary cutaneous mucinous carcinoma arising on a background of
      extramammary Paget disease of the vulva and perineum.

PMID- 21885945
TI  - The histopathological feature of the nail isthmus in an ectopic nail.
AB  - The nail unit has a unique structure. It has been recently proposed that the nail
      isthmus as a transitional zone between the most distal part of the nail bed and
      the hyponychium. A 7-year-old Japanese boy presented with an ectopic nail, an
      additional and independent miniature nail on the digital pulp of the right fifth
      finger. We studied the expression of a series of keratin in longitudinal
      specimens and showed the histopathological manifestation in the nail isthmus.
      This region in the ectopic nail is subdivided into 2 parts: a proximal and narrow
      part anchored to the nail plate and a distal and wide part with a semihard
      keratinized structure.

PMID- 21885946
TI  - Accidental chopstick injury resulting in internal capsule lesion and
      intracerebral hemorrhage.

PMID- 21885947
TI  - Assessing weakness in patients with ulnar neuropathy: comparison between a custom
      hand muscle dynamometer and a pinch dynamometer.
AB  - OBJECTIVE: The aim of this study was to compare the use of a custom intrinsic
      hand dynamometer (HD) with that of a standard pinch dynamometer (PD) in assessing
      strength in patients with ulnar neuropathy at the elbow. DESIGN: Nine patients
      (age, 53 +/- 3 yrs) with clinical and electrophysiological features of ulnar
      neuropathy at the elbow with conduction block (CB) were studied. All underwent
      bilateral ulnar motor nerve conduction studies recording from the first dorsal
      interosseous and a quantitative measurement of strength of the first dorsal
      interosseous using a custom-made HD and a standard PD. RESULTS: The maximal
      strength of the ulnar neuropathy at the elbow-affected side (16.2 +/- 8.0 N) was
      found to be significantly lower than that of the unaffected side (27.9 +/- 11.2
      N), as measured by HD. Strength differences were not significant between the
      affected (62.7 +/- 26.4 N) and unaffected sides (48.0 +/- 20.5 N) using PD. HD
      force decrement (in comparison with the unaffected limb) correlated strongly with
      CB percentage (r = 0.74). No relationship was found between PD and CB (r = 0.05).
      CONCLUSIONS: HD was better able to measure the weakness of affected muscles than
      did PD, and its results correlated well with the extent of electrophysiological
      CB. Therefore, a custom HD would provide a better indication of disease severity,
      progression, or improvement in strength in studies of ulnar neuropathy at the
      elbow with CB.

PMID- 21885948
TI  - Regulatory policies, the "75% rule," and post-acute care discharge setting.

PMID- 21885949
TI  - Precision of novice sonographers concerning median nerve and Achilles tendon
      measurements.
AB  - OBJECTIVE: The aim of this study was to quantify how precise the measurements of
      beginner sonographers (relative to an expert) are concerning small and large
      ellipsoid structures (median nerve and Achilles tendon). DESIGN: During a 4-day
      musculoskeletal ultrasonography course at a secondary-care center, 19 attendants
      and an expert physiatrist sonographer were enrolled. After the hand practice
      session, the physicians performed median nerve measurements (short axis, long
      axis, and cross-sectional area) at the level of carpal tunnel on the same
      subject. Repeat measurements were done at the end of the following day.
      Similarly, achilles tendon measurements were taken during 2 consecutive days
      (after the ankle-foot session). An expert sonographer also performed the same
      evaluations twice, together with the attendants. The mean values of the expert's
      measurements were used as the "test value" for each parameter. RESULTS: Median
      nerve long-axis values pertaining to the first trial were found to be smaller
      than that of the test value (P = 0.003), but those of the second trial were
      similar to the test value (P = 0.107). Median nerve short-axis and area
      measurements were not different from the test value in either trials (P > 0.05).
      Achilles tendon measurements were significantly larger than the test value (P <
      0.05) at the first trial but were similar to the test value at the second trial
      (P > 0.05). Percentage deviations of the attendants' measurements (median nerve
      short and long axes) were negatively correlated with their sonography experience.
      CONCLUSIONS: We imply that novice sonographers tend to measure small structures
      smaller and large structures larger. Personal experience seems to play a role
      especially for small structures, and practice affects the precision of these
      measurements favorably.

PMID- 21885950
TI  - Painful congestion of the lower limbs and recurrent fever.
AB  - We describe a 45-year-old patient with massive pain and congestion in the lower
      limbs. In addition, he daily presented fever up to 39.5 degrees C (103.1 degrees
      F) without any infectious focus for 8 days. A formerly unknown vena cava atresia
      with severe bilateral deep vein thrombosis and concomitant heterozygous
      prothrombin (factor II) gene mutation (G20210A) was diagnosed during the hospital
      stay. Because of the severe clinical findings and hereditary thrombophilia, we
      recommended a lifelong anticoagulant therapy and elastic stockings. Furthermore,
      different diagnosis and treatment strategies are discussed in case of concomitant
      prothrombin gene mutation.

PMID- 21885951
TI  - Anticoagulant-resistant thrombophilia in a patient with polycythemia vera:  a
      case report.
AB  - Mechanical valve thrombosis is a rare condition in an adequately anticoagulated
      patient in the absence of underlying thrombophilia. We report a case of a 76-year
      old male with mechanical prosthetic mitral valve thrombosis as the presenting
      feature of polycythemia vera. The patient was treated with thrombolysis at the
      time of acute presentation and subsequently maintained on low molecular weight
      heparin, low-dose aspirin, phlebotomy and hydroxyurea. Hemoglobin, leucocytosis
      and platelet count were controlled for almost 4 years after which the patient
      suffered a second, fatal episode in the setting of therapeutic anti-Xa level.
      This case report highlights the thrombotic risks associated with polycythemia
      vera. The proposed mechanisms of hypercoagulability in polycythemia vera are
      reviewed. To the best of our knowledge, mechanical valve thromboses as the
      presenting feature of polycythemia vera has not been reported previously.

PMID- 21885952
TI  - A novel splice-site mutation c.42-2A>T (IVS1-2A>T) of SERPINC1 in a Korean family
      with inherited antithrombin deficiency.
AB  - Inherited antithrombin (AT) deficiency (OMIM 107300) is an autosomal dominant
      disorder and causes a 20-fold increase in the risk of venous thromboembolism.
      Herein, we describe a case of a novel splice-site mutation in the SERPINC1 gene
      in a Korean patient with inherited AT deficiency. The patient was a 35-year-old
      woman who presented with deep vein thrombosis (DVT) and pulmonary embolism and
      was without a recent history of any precipitating factors. The obtaining of her
      family history revealed that her mother had an ischemic stroke and a pulmonary
      embolism and her two sisters both had an episode of DVT during pregnancy. DNA
      sequencing of SERPINC1 revealed the novel variant IVS1-2A>T (c.42-2A>T), a
      substitution in intron 1, in the proband and her daughter. The mutation IVS1-2A>T
      eliminates the acceptor splice-site of intron 1. The present case is the first
      novel splice-site mutation of SERPINC1 in a Korean family with inherited AT
      deficiency.

PMID- 21885953
TI  - Diagnosis and classification of von Willebrand disease:  a review of the
      differential utility of various functional von Willebrand factor assays.
AB  - von Willebrand disease (VWD) is considered to be the most common inherited
      bleeding disorder. VWD is diagnosed following a clinical and physical review,
      with personal and familial evidence of (primarily mucocutaneous) bleeding, and
      confirmed by laboratory testing. The latter typically entails initial plasma
      testing of factor VIII coagulant, von Willebrand factor (VWF) protein ('antigen')
      and VWF function which has classically been assessed using the ristocetin
      cofactor (VWF:RCo) assay. More recent attention has focussed on other functional
      VWF assays, such as collagen binding and so-called 'VWF activity' assays, as
      possible replacements to the VWF:RCo, or as supplementary tests of VWF
      'function'. Additional laboratory testing can comprise a battery of confirmatory
      and VWD-type assisting assays, including VWF:multimer and von Willebrand factor
      VIII binding. This review aims to update knowledge of current VWD diagnostics
      with a particular emphasis on 'functional' VWF assays.

PMID- 21885954
TI  - Acquired haemophilia A in a woman with autoimmune hepatitis and systemic lupus
      erythematosus:  review of literature.
AB  - Acquired haemophilia A, secondary to systemic lupus erythematosus (SLE), is a
      rare bleeding diathesis. Here we report a 37-year-old woman with autoimmune
      hepatitis who developed SLE and acquired haemophilia caused by factor VIII
      (fVIII) inhibitors. She presented with spontaneous ecchymosis and haematuria.
      There were a prolongation of the activated partial thromboplastin time, reduced
      fVIII activity and a high titre of fVIII inhibitors. Therapeutic regimen was
      started with intravenous methylprednisolone pulse, continued with prednisolone,
      intravenous pulse cyclophosphamide and fresh frozen plasma. After 8 weeks, fVIII
      inhibitor assay was negative.

PMID- 21885955
TI  - Formation of obstructing blood clot in the ureter in a patient with Glanzmann's
      thrombasthenia.
AB  - Glanzman thrombasthenia is a rare hematologic disorder characterized by
      qualitative thrombocyte abnormality. Patients present with episodic mucocutaneous
      bleeding. Thrombosis is a paradox phenomenon observed in patients with Glanzman
      thrombasthenia and generally considered as a treatment complication. We present a
      16-year-old girl referred for severe flank pain beginning after treatment of
      hematuria due to Glanzman thrombasthenia. The patient underwent endoscopy for
      further diagnosis and treatment because of the failure of radiologic evaluation.
      Although the resolution of the large clots was obtained with streptokinase
      instillation via the ureteral catheter, clot was mobilized with gentle insertion
      of ureteral catheter in the present case.

PMID- 21885956
TI  - Deep vein thrombosis induced by thalidomide to control epistaxis secondary to
      hereditary haemorrhagic telangiectasia.
AB  - Thalidomide was recently reported to reduce the severity and frequency of
      epistaxes in patients with hereditary haemorrhagic telangiectasia (HHT). We here
      describe the case of a patient with HHT and severe epistaxes refractory to
      medical and local surgical treatments who developed an extensive deep vein
      thrombosis shortly after initiation of treatment with thalidomide. This is the
      first report of venous thromboembolic complication induced by thalidomide
      prescribed in this setting. Although thalidomide was recently found to provide an
      alternative therapeutic strategy in patients with HHT and refractory epistaxes,
      this agent should be used with great caution in this indication, given its
      thrombogenicity and difficulties to manage systemic anticoagulation in patients
      with HHT.

PMID- 21885957
TI  - Heparin in the long-term management of ligneous conjunctivitis:  a case report
      and review of literature.
AB  - Ligneous conjunctivitis, secondary to inherited homozygous plasminogen
      deficiency, is a poorly understood condition that has the potential to hinder
      normal childhood development if not managed adequately. We report the clinical
      progression of a child with ligneous conjunctivitis, controlled with daily
      heparin eye drops, postsurgical excision, for a duration of approximately 5 years
      at a cost of approximately 30 USD per month. During this time, the patient's
      progress has been complicated by one occurrence of periorbital cellulitis and
      also otitis media. The patient has also experienced ocular complications due to
      the remaining membranous lesion. This case indicates that individual patient
      factors including plasminogen levels and exposure to triggers of ocular
      inflammation may influence the clinical progression of ligneous conjunctivitis.
      Furthermore, this study is one of the first to present over 5-year follow-up of a
      patient with ligneous conjunctivitis effectively managed with long-term heparin
      eye drops.

PMID- 21885958
TI  - Ambulatory blood pressure monitoring among patients with cerebrovascular disease.
AB  - BACKGROUND: Although stroke care guidelines endorse the paramount importance of
      hypertension management, the specific role of ambulatory blood pressure (ABP)
      monitoring among patients with cerebrovascular disease has not been established.
      OBJECTIVES: The objectives of this study were to: (a) conduct a systematic review
      describing the published studies that examined ABP monitoring among patients with
      cerebrovascular disease and (b) to discuss practical considerations of ABP
      monitoring among patients with stroke. METHODS: We identified English-language
      articles that focused on the use of ABP monitoring among patients with
      cerebrovascular disease. The titles and abstracts of the articles were reviewed
      to identify whether the study included ABP monitoring and whether the populations
      studied had evidence of cerebrovascular disease; we excluded two case reports. We
      used ABP data from patients with cerebrovascular disease enrolled in an ongoing
      clinical trial to illustrate points related to the application of ABP monitoring
      in this population. RESULTS: A total of 23 articles met our inclusion criteria.
      These articles described the use of ABP monitoring for the identification of
      stroke patients at risk of poor outcomes, including mortality and neurological
      impairment. They also describe common patterns of blood pressure poststroke;
      finding that stroke patients often demonstrate a loss of the usual nocturnal fall
      in blood pressure. Logistical considerations in the use of ABP monitoring for
      patients with stroke include patients with arm weakness, the minimum number of
      measurements needed, the determination of nocturnal/rest versus daytime/wake
      blood pressure values, and the interpretation of extreme values are reviewed.
      CONCLUSION: Until controlled trial data support interventions based on the ABP
      data, it is unlikely that guidelines will recommend the routine application of
      ABP monitoring among patients with stroke.

PMID- 21885959
TI  - Validation of the UEBE Visomat Double Comfort upper arm blood pressure monitor,
      in oscillometric mode, for clinic use and self-measurement in a general
      population according to the European Society of Hypertension International
      Protocol, revision 2010.
AB  - OBJECTIVE: To validate the UEBE Visomat Double Comfort, an upper arm blood
      pressure monitor designed for self-measurement of blood pressure and for clinical
      use in a general population according to the European Society of Hypertension
      International Protocol revision 2010. METHODS: The device is provided with two
      operational modalities, a microphonic mode and an oscillometric mode. In this
      study, the oscillometric modality was tested. Device evaluation was performed in
      33 participants with a mean +/- standard deviation age of 56.3 +/- 20.0 years
      (range, 25-85 years). Their systolic blood pressure was 140.4 +/- 27.7 mmHg,
      diastolic blood pressure was 86.8 +/- 17.2 mmHg, and arm circumference was 29.3
      +/- 3.9 cm. RESULTS: The protocol requirements were followed precisely. The
      device passed all of the requirements fulfilling the standards of the protocol.
      Mean blood pressure differences between device and observer were -0.9 +/- 4.1
      mmHg for systolic blood pressure and -0.1 +/- 3.3 mmHg for diastolic blood
      pressure. CONCLUSION: As the Visomat Double Comfort in the oscillometric modality
      has achieved the required standards, it is recommended for clinical use in an
      adult population.

PMID- 21885960
TI  - Application of Nexfin noninvasive beat-to-beat arterial blood pressure monitoring
      in autonomic function testing.
AB  - OBJECTIVE: Evaluation of autonomic function responses is increasingly important
      for risk prediction and hemodynamic evaluation in the ambulant and perioperative
      setting, but requires a noninvasive arterial blood pressure measurement device.
      This study describes whether a novel noninvasive beat-to-beat arterial blood
      pressure measurement device (Nexfin HD) is able to reproducibly reflect autonomic
      function responses in healthy volunteers. METHODS: Noninvasive beat-to-beat
      arterial blood pressure measurements (Nexfin HD) were performed in 20 healthy men
      of 22 +/- 3 years. Measurements were performed during supine steady state,
      controlled breathing (0.125 Hz), passive leg raising, a controlled Valsalva
      maneuver, and a quick stand test. Finally, relative changes in pulse pressure
      during autonomic function testing and the test-retest reproducibility were
      determined. RESULTS: Autonomic function tests induced beat-to-beat arterial blood
      pressure changes that were accurately monitored by the Nexfin device. The
      intraclass correlation coefficients for systolic and diastolic arterial blood
      pressure measurements during supine steady state were agreeable [0.91 (0.82-0.96)
      and 0.84 (0.69-0.93), respectively]. The reproducibility of blood pressure
      changes during controlled breathing, passive leg raising, and Valsalva maneuver
      averaged 0.92 (0.82-0.96), 0.76 (0.50-0.90), and 0.94 (0.89-0.97), respectively.
      The reproducibility of the pulse pressure variation (PPV) as calculated from
      controlled breathing-induced changes in the arterial blood pressure (13 +/- 5%)
      was high [0.96 (0.93-0.98)]. CONCLUSION: This study shows that noninvasive beat
      to-beat Nexfin HD arterial blood pressure measurements reproducibly reflect
      autonomic function responses in healthy volunteers.

PMID- 21885961
TI  - Accuracy of Microlife WatchBP Office ABI monitor assessed according to the 2002
      European Society of Hypertension protocol and the British Hypertension Society
      protocol.
AB  - OBJECTIVE: To determine the accuracy of the WatchBP Office ABI monitor for blood
      pressure measurement developed by the Microlife Company. METHODS: The device
      accuracy was tested in 85 subjects with a mean age of 54 +/- 19 years. Their
      systolic and diastolic blood pressure (SBP/DBP) at entry was 141 +/- 30/86 +/- 19
      mmHg, and upper arm circumference was 28 +/- 5 cm. Initially, the data from 33
      participants were examined according to the 2002 version of the European Society
      of Hypertension (ESH) protocol. An additional 52 subjects were then enrolled to
      fulfill the requirements of the British Hypertension Society (BHS) protocol. In
      all participants, sequential same arm measurements were performed by two trained
      observers. RESULTS: The device passed all three phases of the ESH protocol for
      SBP and DBP. For the BHS protocol the device was graded A for both SBP and DBP.
      The A/A grade was achieved in the low blood pressure category (< 130/80 mmHg),
      the B/A grade in the medium category (130-160/80-100 mmHg) and the A/A grade in
      the high category (> 160/100 mmHg). Mean blood pressure difference between device
      and observers in the first 33 subjects was -0.9 +/- 5.5 mmHg for SBP and -2.2 +/-
      4.5 mmHg for DBP and in the 85 participants it was -1.2 +/- 6.5 mmHg and -2.3 +/-
      5.1, respectively. CONCLUSION: These data show that the Microlife WatchBP Office
      ABI monitor satisfied the recommended ESH accuracy levels and achieved A/A grade
      of the BHS protocol across a wide range of BP.

PMID- 21885962
TI  - Physicians' determinants for sick-listing LBP patients: a systematic review.
AB  - STUDY DESIGN: A systematic review of the literature. OBJECTIVES: Sick-listing is
      a complex process that involves stakeholders at several levels. Although the
      physicians are the ones who issue a sick note, little is known about the
      mechanisms and determinants they use in making a decision about whether to sick
      list a patient with low back pain (LBP). The aim of this systematic review is to
      describe the evidence on determinants used by physicians to sick-list patients
      with LBP. METHODS: Electronic searches of Medline, EMBASE, PsychInfo, and
      Cochrane Central were conducted (all years to June 2011). Inclusion criteria
      included studies of workers with LBP presenting to a physician where sick-listing
      certification was an outcome of the consultation process. Studies were critically
      appraised for their internal validity by 2 independent reviewers using a modified
      version the criteria proposed by Hayden et al. Findings from papers were
      synthesized into internal and external factors related to the physician. RESULTS:
      The search identified 1419 unique citations from which 11 papers met the
      inclusion criteria. The evidence suggests that 2 internal factors are important
      determinants of sick listing: physicians' personal fear avoidance and distress
      regarding the complexity of LBP. External factors included patients'
      expectations, the presence of clinical findings, and the support and general
      attitude demonstrated by a patients' employer and the availability of modified
      work. CONCLUSIONS: The current review suggests that physicians need to improve
      their knowledge regarding options for modified work in the workplace, and about
      the management of LBP in general. The otherwise beneficial patient-physician
      relationship and physicians' care for their patients may be an obstacle to
      following guidelines on LBP management in the sick-listing process. Future
      studies should address these issues.

PMID- 21885963
TI  - EMG assessment of analgesia in treatment of posttonsillectomy pain: random
      allocation, preliminary report.
AB  - OBJECTIVES: Surface electromyographic (sEMG) study of posttonsillectomy swallow
      evoked muscular reactions was performed to assess validity of EMG in evaluation
      of analgesic drugs. METHODS: Sixty randomly chosen operated adults were divided
      into group 1 (n=30) treated with oxycodone, and group 2 (n=30) treated with
      placebo. Pain assessment included visual analog scale (VAS) pain score and EMG
      data: the timing, electric amplitude, and graphic patterns of muscular activity.
      We investigated masseter, infrahyoid, and submental-submandibular muscles.
      Records from trapezius muscle were used for control. The results were compared
      with previously established normative database. The sEMG data were compared with
      VAS score. RESULTS: Oxycodone significantly reduced VAS pain score and changed
      muscle reactions to analgesia (amplitude) as was recorded by sEMG, whereas
      placebo reduced VAS pain score nonsignificantly and changed the reaction of the
      trapezius muscle only. Analgesia smoothes the recorded swallow peaks and
      increases time of deglutition. Statistically significant difference in muscle
      reactions was detected between the 2 groups. CONCLUSIONS: sEMG might be used for
      quantitative evaluation of analgesic drugs by assessment of muscular reactions to
      pain and to analgesia. This method might add quantitative justification to the
      information obtained by VAS pain testing and clinical data.

PMID- 21885964
TI  - The Boston keratoprosthesis in the management of corneal limbal stem cell
      deficiency.
AB  - PURPOSE: To report the outcomes of the Boston type I keratoprosthesis
      (Massachusetts Eye and Ear Infirmary, Boston, MA) in the management of corneal
      limbal stem cell deficiency (LSCD). METHODS: A retrospective review of all cases
      of keratoprosthesis implantation performed by a single surgeon (A.J.A.) between
      May 1, 2004, and March 31, 2010. Procedures performed for the management of LSCD
      were identified, and data were collected regarding the patients' ocular history,
      surgical procedure(s) performed, and postoperative outcomes, including interval
      visual acuities, retention, complications, and required surgical procedures. The
      outcome data from patients with LSCD were compared with those of individuals who
      underwent keratoprosthesis implantation for indications other than LSCD. RESULTS:
      Twenty-eight keratoprostheses were performed in 23 eyes of 22 patients with LSCD.
      The most common indications for surgery were chemical injury (7 eyes) and Stevens
      Johnson syndrome (6 eyes). Preoperative corrected distance visual acuity (CDVA)
      was better than counting fingers in 4% of eyes with LSCD and in 9% of eyes
      without LSCD. Postoperative CDVA was 20/50 or better in 69%, 88%, and 67% of eyes
      with LSCD at 1, 2, and 3 years after keratoprosthesis implantation, respectively.
      Each of these percentages is higher than the percentage of eyes without LSCD
      obtaining CDVA of 20/50 or better at each time point. Whereas the retention
      failure rate in eyes with LSCD (0.148/eye-year) was higher than the rate in eyes
      without LSCD (0.114/eye-year), when eyes with Stevens-Johnson syndrome were
      excluded from the LSCD group, the non-Stevens-Johnson syndrome LSCD retention
      failure rate (0.056/eye-year) was half that of the non-LSCD group. The most
      common postoperative complications in eyes with LSCD were persistent corneal
      epithelial defect (PED) formation (56.5% of eyes) and sterile corneal necrosis
      (30%), whereas retroprosthetic membrane formation (46%) was the most common
      postoperative complication in eyes without LSCD, followed by PED formation (23%).
      The development of a PED was found to be a significant risk factor for sterile
      corneal stromal necrosis and infectious keratitis. CONCLUSION: Boston type I
      keratoprosthesis implantation results in a significant improvement in CDVA in the
      majority of patients with LSCD, with CDVA of 20/50 or better in more than two
      thirds of eyes up to 3 years after surgery. PED formation is the most common
      postoperative complication in eyes with LSCD and is associated with an increased
      rate of sterile stromal necrosis and a lower retention rate in eyes undergoing
      keratoprosthesis implantation for immune-mediated LSCD. These results support the
      use of the Boston type I keratoprosthesis in managing bilateral, non-immune
      mediated LSCD.

PMID- 21885965
TI  - Progressive growth in epibulbar complex choristomas: report of 2 cases and review
      of literature.
AB  - PURPOSE: To report 2 patients with progressive complex choristomas and to review
      the literature on this subject. DESIGN: Interventional case reports. METHODS:
      Clinical and pathologic correlation was performed on 2 patients with progressive
      epibulbar choristomas. PubMed database was searched to identify all the
      previously reported cases of progressive epibulbar choristomas (using key words
      choristoma, dermoid, growth, progression, and evolution). RESULTS: Growth of the
      epibulbar choristomas was noted in infancy in 1 patient with oculoectodermal
      syndrome and in puberty in another otherwise healthy patient. Both lesions were
      identified histopathologically as complex choristomas. In addition to the
      characteristic choristomatous tissues, both lesions demonstrated increased
      vascularity, inflammatory infiltrate, and fibroblast proliferation within
      myxomatous stroma. Review of the literature identified 4 patients with
      progressive complex choristomas, 1 of whom demonstrated histopathologic findings
      similar to those of the 2 cases reported here. CONCLUSIONS: Epibulbar choristomas
      rarely enlarge, likely secondary to reactive changes within the tissue manifested
      by increased vascularity, inflammatory cell infiltration, and fibroblast
      proliferation with deposition of myxomatous stroma.

PMID- 21885966
TI  - New insights into uremia-induced alterations in metabolic pathways.
AB  - PURPOSE OF REVIEW: This article summarizes recent studies on uremia-induced
      alterations in metabolism, with particular emphasis on the application of
      emerging metabolomics technologies. RECENT FINDINGS: The plasma metabolome is
      estimated to include more than 4000 distinct metabolites. Because these
      metabolites can vary dramatically in size and polarity and are distributed across
      several orders of magnitude in relative abundance, no single analytical method is
      capable of comprehensive metabolomic profiling. Instead, a variety of analytical
      techniques, including targeted and nontargeted liquid chromatography-mass
      spectrometry, have been employed for metabolomic analysis of human plasma. Recent
      efforts to apply this technology to study uremia have reinforced the common view
      that end-stage renal disease is a state of generalized small molecule excess.
      However, the identification of precursor depletion and downstream metabolite
      excess - for example, with tryptophan and downstream kynurenine metabolites, with
      low molecular weight triglycerides and dicarboxylic acids, and with
      phosphatidylcholines, choline, and trimethylamine-N-oxide - suggest that uremia
      may directly modulate these metabolic pathways. Metabolomic studies have also
      begun to expand some of these findings to individuals with chronic kidney disease
      and in model systems. SUMMARY: Uremia is associated with diverse, but
      incompletely understood metabolic disturbances. Metabolomic approaches permit
      higher resolution phenotyping of these disturbances, but significant efforts will
      be required to understand the functional significance of select findings.

PMID- 21885967
TI  - Urinary proteomics in the assessment of chronic kidney disease.
AB  - PURPOSE OF REVIEW: Urinary proteomics has emerged as an approach that could
      deliver relevant clinical information. In this review, we aim at highlighting the
      recent developments, especially with respect to clinical implementation. We
      review several of the recent publications reporting on larger cohorts, focusing
      on those that aim at qualification and/or validation of urinary proteomics
      biomarkers. RECENT FINDINGS: Several components of the urinary proteome,
      especially its low molecular weight fraction (sometimes referred to as the
      'peptidome'), have been significantly associated with chronic kidney disease
      (CKD). Independent studies, encompassing sometimes close to 1000 independent
      samples, indicate that specific peptides from extracellular matrix (ECM) proteins
      encompass a major component of the urinary proteome. Highly significant changes
      in the abundance of some of these peptides are associated with CKD indicating
      that alterations in ECM, reflected via the urinary proteome, may represent an
      early stage in CKD pathology. These peptides may serve as specific early
      biomarkers, and interference with pathological ECM accumulation may be a valuable
      new therapeutic approach in CKD. SUMMARY: Urinary proteomic biomarkers have
      emerged as clinically relevant variables. First studies involving several hundred
      individuals indicate a potential added benefit of urinary proteomic biomarkers.
      First large clinical trials are being initiated to employ urinary proteomics in
      clinical decision making.

PMID- 21885968
TI  - Renal sympathetic denervation in hypertension.
AB  - PURPOSE OF REVIEW: Despite the abundance of antihypertensive drugs, resistant
      hypertension remains a major clinical problem. Recent technological advances
      render interventional management of resistant hypertension one of the hottest
      topics in the hypertension field. The aim of this review is to present the
      pathophysiologic background and the mechanisms mediating blood pressure reduction
      after renal sympathetic denervation, to analyze recent findings with this
      fascinating approach and to critically suggest future research directions. RECENT
      FINDINGS: Catheter-based, ablation-induced renal sympathetic denervation was
      initially studied in 45 patients with resistant hypertension in a proof-of
      concept study. Impressive blood pressure reductions of about 30/15  mmHg were
      achieved at 6 months, without serious complications. A second, controlled,
      randomized (but not blinded) study confirmed the results, verifying the efficacy
      and safety of the procedure. A recent report revealed the 2-year durability of
      blood pressure reduction. SUMMARY: Data published so far indicate that ablation
      induced renal denervation is a feasible, effective, and well tolerated
      interventional approach for the management of resistant hypertension. The
      groundbreaking studies of renal denervation in drug-resistant hypertension pave
      the way for further research in other disease conditions in which sympathetic
      overactivity seems to play a critical role. This initial wave of enthusiasm needs
      to be followed by rigorous investigation, for the proper identification of the
      potential and the limitations, indications, and contraindications of this
      approach.

PMID- 21885969
TI  - Calcineurin inhibitors in kidney transplantation:  friend or foe?
AB  - PURPOSE OF REVIEW: The utilization of calcineurin inhibitors (CNI) in kidney
      transplantation has dramatically improved short-term outcomes but significant
      gains in long-term outcomes have proved elusive. Nephrotoxicity is the major
      problem associated with CNIs and is responsible for the disappointing progress
      seen in long-term graft survival. In this review, we assess CNI efficacy as well
      as the latest strategies employed to limit long-term CNI nephrotoxicity. RECENT
      FINDINGS: Three CNI sparing strategies - CNI withdrawal, CNI avoidance, and CNI
      minimization - are evaluated with discussion of key studies such as the Efficacy
      Limiting Toxicity Elimination-Symphony and Spare-the-Nephron studies. Recent
      breakthroughs in transplant immunosuppression are discussed such as the BENEFIT
      and BENEFIT-EXT studies, which have led to the recent US Food and Drug
      Administratrion approval of belatacept, a novel T-cell costimulation blocker.
      SUMMARY: For now, CNIs remain the proven standard of care in modern
      immunosuppression. However, some novel agents may challenge the role CNIs play in
      kidney transplantation in the very near future.

PMID- 21885971
TI  - MRI to assess renal structure and function.
AB  - PURPOSE OF REVIEW: In addition to excellent anatomical depiction, MRI techniques
      have expanded to study functional aspects of renal physiology, such as renal
      perfusion, glomerular filtration rate (GFR) or tissue oxygenation. This review
      will focus on current developments with an emphasis on clinical applicability.
      RECENT FINDINGS: The method of GFR determination is largely heterogeneous and
      still has weaknesses. However, the technique of employing liver disappearance
      curves has been shown to be accurate in healthy persons and patients with chronic
      kidney disease. In potential kidney donors, complete evaluation of kidney anatomy
      and function can be accomplished in a single-stop investigation. Techniques
      without contrast media can be utilized to measure renal tissue oxygenation (blood
      oxygen level-dependent MRI) or perfusion (arterial spin labeling) and could aid
      in the diagnosis and treatment of ischemic renal diseases, such as renal artery
      stenosis. Diffusion imaging techniques may provide information on spatially
      restricted water diffusion and tumor cellularity. SUMMARY: Functional MRI opens
      new horizons in studying renal physiology and pathophysiology in vivo. Although
      extensively utilized in research, labor-intensive postprocessing and lack of
      standardization currently limit the clinical applicability of functional MRI.
      Further studies are necessary to evaluate the clinical value of functional
      magnetic resonance techniques for early discovery and characterization of kidney
      disease.

PMID- 21885970
TI  - Measurement of insulin resistance in chronic kidney disease.
AB  - PURPOSE OF REVIEW: Insulin resistance is a known complication of end-stage renal
      disease that also appears to be present in earlier stages of chronic kidney
      disease (CKD). It is a risk factor for cardiovascular disease and an important
      potential therapeutic target in this population. Measurement of insulin
      resistance is reviewed in the context of known pathophysiologic abnormalities in
      CKD. RECENT FINDINGS: Insulin resistance in CKD is due to a high prevalence of
      known risk factors (e.g. obesity) and to unique metabolic abnormalities. The site
      of insulin resistance in CKD is localized to skeletal muscle. Estimates based on
      fasting insulin concentration may not adequately capture insulin resistance in
      CKD because they largely reflect hepatic defects and because CKD impairs insulin
      catabolism. A variety of dynamic tests are available to directly measure insulin
      mediated glucose uptake. SUMMARY: Insulin resistance may be an important
      therapeutic target in CKD. Complementary methods are available to assess insulin
      resistance, and each method has unique advantages, disadvantages, and levels of
      complexity. These characteristics, and the likelihood that CKD alters the
      performance of some insulin resistance measurements, must be considered when
      designing and interpreting clinical studies.

PMID- 21885972
TI  - State of the art:  what we know about infectious agents and myositis.
AB  - PURPOSE OF REVIEW: Increasing evidence suggests that the idiopathic inflammatory
      myopathies (IIMs) result from certain environmental exposures in genetically
      susceptible individuals. Investigations have demonstrated that a variety of
      infections not only cause infectious myopathies but also could be possible
      triggers for IIM. This review summarizes published studies on the possible roles
      of infections in inflammatory muscle disease. RECENT FINDINGS: Many infectious
      agents have been linked to the development of IIMs via case reports,
      epidemiologic investigations, and animal models. Additional agents possibly
      involved in triggering the development of IIMs have been recently described,
      including Torque teno virus (TTV) and Borrelia burgdorferi. Novel animal models
      of myositis have been recently developed using Leishmania infantum or Chikungunya
      virus (CHIKV). New technologies to assess infectious agents include high
      throughput methods for pathogen identification and novel approaches to identify
      gene expression of pathogens in tissues. SUMMARY: Understanding the causes of
      IIMs remains limited in part due to the rarity and heterogeneity of these
      disorders. Although no definitive studies have yet linked infectious agents with
      IIMs, additional evidence is accumulating and novel technologies may allow
      improved understanding of the roles of infections in IIMs and for possible future
      therapeutic and preventive measures.

PMID- 21885973
TI  - Inclusion body myositis.
AB  - PURPOSE OF REVIEW: Sporadic inclusion body myositis (sIBM) is a poorly understood
      immune and degenerative disease of skeletal muscle. Here, current opinion of the
      nature of this disease is summarized. RECENT FINDINGS: Recent findings for sIBM
      include further characterization of muscle involvement through magnetic resonance
      imaging, the role of muscle as a host for immune cells, progress in the role of
      extranuclear TDP-43 in causing cellular injury, and the discovery of a new sIBM
      autoantibody. SUMMARY: sIBM understanding continues to advance, with progress
      regarding the mechanism of this disease.

PMID- 21885974
TI  - beta-catenin signaling:  a novel mediator of fibrosis and potential therapeutic
      target.
AB  - PURPOSE OF REVIEW: The Wnt/beta-catenin signaling pathway plays a critical role
      in development and adult tissue homeostasis. Recent investigations implicate
      Wnt/beta-catenin signaling in abnormal wound repair and fibrogenesis. The purpose
      of this review is to highlight recent key studies that support a role for
      Wnt/beta-catenin signaling in fibrosis. RECENT FINDINGS: Studies of patients with
      fibrotic diseases have demonstrated changes in components of the Wnt/beta-catenin
      pathway. In animal models, perturbations in Wnt/beta-catenin signaling appear to
      aggravate or ameliorate markers of injury and fibrosis in a variety of different
      tissues. Studies also suggest that fibroblasts from different tissue sources may
      have markedly divergent responses to Wnt/beta-catenin signaling. Cross-talk
      between Wnt/beta-catenin and transforming growth factor-beta pathways is complex
      and context-dependent, and may promote fibrogenesis through coregulation of
      fibrogenic gene targets. High throughput screening has identified several novel
      chemical inhibitors of Wnt/beta-catenin signaling that may be of therapeutic
      potential. SUMMARY: Wnt/beta-catenin signaling appears important in normal wound
      healing and its sustained activation is associated with fibrogenesis. The
      mechanism by which Wnt/beta-catenin signaling may modify the response to injury
      is cell-type and context-dependent. Better understanding of this signaling
      pathway may provide a promising new therapeutic approach for human fibrotic
      diseases.

PMID- 21885975
TI  - Necrotizing autoimmune myopathy.
AB  - PURPOSE OF REVIEW: Necrotizing autoimmune myopathy (NAM) is a relatively newly
      recognized subgroup of idiopathic inflammatory myopathies, which despite diverse
      causes, have the common histopathological features of myocyte necrosis without
      significant inflammation. Patients present with a subacute severe symmetrical
      proximal myopathy, associated with a markedly elevated creatine kinase level.
      These are most likely immune-mediated, as they respond to immunotherapy. The
      review aims to define this heterogeneous entity and summarize the salient
      clinical, laboratory, and muscle biopsy findings, in order to facilitate the
      diagnosis and treatment of this condition. RECENT FINDINGS: Statin-associated NAM
      has been linked with an antibody against the 3-hydroxy-3-methylglutaryl-coenzyme
      A reductase (HMGCR) protein, which is up-regulated in regenerating fibres. This
      finding suggests that NAM is an antibody-mediated disease, and may explain the
      continuing progression of disease despite cessation of the statin. In addition it
      may provide a useful diagnostic test in the future, to help differentiate immune
      from nonimmune statin myopathies. SUMMARY: It is important to recognize and
      distinguish NAM from other causes of myocyte necrosis, because it has the
      potential of being amenable to treatment.

PMID- 21885976
TI  - An update on an immune system that goes awry in systemic sclerosis.
AB  - PURPOSE OF REVIEW: This review aims to provide an overview of the recent data
      that emerged, further substantiating the critical role of innate immunity in
      systemic sclerosis (SSc). RECENT FINDINGS: Driven by the evidence that newly
      identified SSc susceptibility genes are predominantly involved in immune
      regulation, we discuss the aberrant antigen presenting cell (APC) activation
      observed in the course of disease. In particular, we report the alternate
      activation of 'M1' and 'M2' macrophages reflecting different clinical phenotypes
      and the aberrant Toll-like receptor (TLR) response, whose effect on cytokine
      production is mostly evident in the early phases of disease; we especially
      highlight the increasing importance attributed to TLR3-mediated fibrosis. We next
      discuss the potential role for interferon (IFN) - producing plasmacytoid
      dendritic cells (pDCs) in triggering or perpetuating the inflammatory loop caused
      by TLR hyperactivation, possibly resulting in inflammasome-derived IL-1beta
      mediated fibrosis and IL-17 producing T helper cells (Th17) skewing. SUMMARY: We
      propose to approach SSc as a multistep immune-mediated disease that is in need of
      a therapeutic strategy designed to interfere with one or more of these aberrant
      molecular pathways. Targeting of DCs could be such a target by which dampening
      the immune system could modify the course of SSc.

PMID- 21885977
TI  - Contemporary management of Raynaud's phenomenon and digital ischaemic
      complications.
AB  - PURPOSE OF REVIEW: The present review gives an update of the current management
      of Raynaud's phenomenon and its ischaemic complications (digital ulceration and
      critical ischaemia) and discusses possible further developments in the next 5-10
      years. New approaches to therapy are being driven by increased understanding of
      pathophysiology and by increased international networking of clinicians and
      scientists, facilitating clinical trials. RECENT FINDINGS: Key points include
      phosphodiesterase inhibitors most likely confer benefit, although clinical trials
      have given somewhat conflicting results, and have been short-term; a new topical,
      easy-to-use glyceryl trinitrate preparation has been shown to improve Raynaud's
      Condition Score; the endothelin-1 receptor antagonist bosentan has now been shown
      to reduce the number of new systemic sclerosis (SSc)-related digital ulcers in
      two multinational clinical trials; and although statin therapy is likely to
      confer benefit in SSc-related Raynaud's phenomenon, further research is required
      to confirm this. SUMMARY: New therapeutic approaches in patients who do not
      respond to more traditionally used vasodilators include phosphodiesterase
      inhibitors and (for those with recurrent SSc-related digital ulcers) endothelin-1
      receptor antagonism. Several other potential new therapies are being researched.
      Optimal management of digital ulceration is multidisciplinary including tissue
      viability and (sometimes) surgical input.

PMID- 21885978
TI  - Anaesthesia by non-anaesthesiologists:  the Pandora Box is open!

PMID- 21885979
TI  - Preoperative iron deficiency increases transfusion requirements and fatigue in
      cardiac surgery patients:  a prospective observational study.
AB  - BACKGROUND: Iron deficiency is the commonest cause of anaemia. It is apparent
      preoperatively in cardiac surgery patients and may influence transfusion
      requirements. In addition, iron deficiency per se is associated with fatigue.
      OBJECTIVE: To determine the prevalence of preoperative iron deficiency and its
      association with perioperative anaemia, blood transfusions and fatigue in cardiac
      surgery patients. SETTING: Academic hospital in Paris, France. PATIENTS: One
      hundred consecutive patients without known iron disorder and scheduled for
      cardiac surgery were prospectively included in this observational study.
      INTERVENTION: No intervention was performed. MEASUREMENTS: A biological iron
      profile (transferrin saturation, ferritin, soluble transferrin receptor and C
      reactive protein) was assessed on the day of surgery. Diagnosis of iron
      deficiency was defined using a previously published algorithm. Patient fatigue
      was assessed before surgery and 1 week afterwards (day 7) using the
      Multidimensional Fatigue Inventory (MFI-20) score that quotes five distinctive
      dimensions of fatigue. RESULTS: Thirty-seven out of 100 patients were diagnosed
      with iron deficiency. These patients were younger [median (first-third quartile)
      63 (43-70) vs. 70 (59-77) years (P = 0.004)], and more often female (51 vs. 21%,
      P = 0.003), than no iron deficiency patients. Preoperative iron deficiency was
      associated with lower preoperative haemoglobin levels (P = 0.006) and higher
      perioperative transfusion rates during the first week (62 vs. 35%, P = 0.019).
      Patients with iron deficiency but without anaemia (n = 25) received more packed
      red blood cells units than those without iron deficiency or anaemia (n = 50) [2
      (0-2) vs. 0 (0-0) units, P < 0.05). Preoperative iron deficiency was associated
      with higher score of physical fatigue on day 7 (P = 0.01). CONCLUSION:
      Preoperative iron deficiency is frequent among cardiac surgery patients and is
      associated with anaemia, higher transfusion requirements and postoperative
      fatigue.

PMID- 21885980
TI  - Nasotracheal intubation using the Blind Intubation Device in anaesthetised adults
      with Mallampati class 3:  a comparison with the Macintosh laryngoscope.
AB  - CONTEXT: We hypothesised that the Blind Intubation Device (BID) would be
      effective for nasotracheal intubation (NTI) in anaesthetised adults with
      Mallampati class 3. We also hypothesised that BID may cause less haemodynamic
      changes due to the avoidance of direct stimulation induced by the Macintosh
      blade. OBJECTIVE: The purpose of the study was to compare the effectiveness of
      the BID with the Macintosh laryngoscope for NTI in anaesthetised adults with
      Mallampati class 3. DESIGN: A prospective randomised controlled study. SETTING:
      Operation unit in a University Hospital in Shanghai. Period of the study was from
      September to November 2010. PATIENTS OR OTHER PARTICIPANTS: Mallampati class 3
      adults requiring NTI for elective oral and maxillofacial surgery were randomly
      assigned to a BID group (n = 25) or a Macintosh laryngoscope group (ML group) (n
      = 25). INTERVENTION: After anaesthesia induction, patients were intubated by a
      single anaesthesiologist experienced in using both devices. MAIN OUTCOME
      MEASURES: The mean arterial pressure (MAP) and heart rate (HR) were recorded at
      specific time points. NTI duration and success rate was compared. Epistaxis
      associated and NTI-associated postoperative complications were assessed. RESULTS:
      Compared with baseline values, there was a significant increase in MAP in both
      the BID and ML groups which persisted significantly longer in the ML group. The
      BID group showed a significantly attenuated MAP value within 30-60 s. The
      difference between the maximum MAP and the post-induction value was significantly
      greater in the ML group than in the BID group (64.4 +/- 16.1 vs. 45.9 +/- 16.1
      mmHg, P = 0.0003). Compared with baseline values, there was a significant
      increase in HR in both groups which persisted longer in the ML group. There was a
      significantly higher first attempt success rate in the BID group compared with
      the ML group (100 vs. 76%, respectively, P = 0.022). The NTI duration was 36 s
      [interquartile range (IQR) 32-40] in the BID group and 33 s (IQR 25.5-41.5) in
      the ML group. Epistaxis during NTI was less frequent and less severe in the BID
      group (P = 0.031). CONCLUSION: In adults with Mallampati class 3, NTI using the
      BID caused an attenuated haemodynamic response and showed a higher success rate
      on the first attempt without increasing adverse events. The BID is an effective
      alternative to the Macintosh laryngoscope for NTI in anaesthetised adults with
      Mallampati class 3. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT
      01170455.

PMID- 21885981
TI  - Preoperative evaluation of the adult patient undergoing non-cardiac surgery:
      guidelines from the European Society of Anaesthesiology.
AB  - The purpose of these guidelines on the preoperative evaluation of the adult non
      cardiac surgery patient is to present recommendations based on available relevant
      clinical evidence. The ultimate aims of preoperative evaluation are two-fold.
      First, we aim to identify those patients for whom the perioperative period may
      constitute an increased risk of morbidity and mortality, aside from the risks
      associated with the underlying disease. Second, this should help us to design
      perioperative strategies that aim to reduce additional perioperative risks. Very
      few well performed randomised studies on the topic are available and many
      recommendations rely heavily on expert opinion and are adapted specifically to
      the healthcare systems in individual countries. This report aims to provide an
      overview of current knowledge on the subject with an assessment of the quality of
      the evidence in order to allow anaesthetists all over Europe to integrate -
      wherever possible - this knowledge into daily patient care. The Guidelines
      Committee of the European Society of Anaesthesiology (ESA) formed a task force
      with members of subcommittees of scientific subcommittees and individual members
      of the ESA. Electronic databases were searched from the year 2000 until July 2010
      without language restrictions. These searches produced 15 425 abstracts. Relevant
      systematic reviews with meta-analyses, randomised controlled trials, cohort
      studies, case-control studies and cross-sectional surveys were selected. The
      Scottish Intercollegiate Guidelines Network grading system was used to assess the
      level of evidence and to grade recommendations. The final draft guideline was
      posted on the ESA website for 4 weeks and the link was sent to all ESA members,
      individual or national (thus including most European national anaesthesia
      societies). Comments were collated and the guidelines amended as appropriate.
      When the final draft was complete, the Guidelines Committee and ESA Board
      ratified the guidelines.

PMID- 21885982
TI  - Volatile rapid sequence induction in morbidly obese patients.
AB  - BACKGROUND AND OBJECTIVE: The interest in bariatric surgery is growing. Morbidly
      obese patients have an increased risk of hypoxia and decreased blood pressure
      during rapid sequence induction (RSI). Alternate RSI methods that provide
      cardiovascular and respiratory stability are required. With this in mind, we
      evaluated a method for volatile RSI in morbidly obese patients. DESIGN:
      Observational study. METHODS: Thirty-four patients with mean BMI 42.4 kg m
      undergoing bariatric surgery (morbidly obese group) and 22 patients with mean BMI
      25.6 kg m as a control group were included in the study. Anaesthesia was induced
      with sevoflurane, propofol, suxamethonium and alfentanil, designed to avoid
      respiratory and haemodynamic adverse events and to minimise depressing effect on
      the brain respiratory centre under ongoing RSI. Peripheral oxygen saturation
      (SpO2) and mean arterial blood pressure were registered before and after
      endotracheal intubation. In addition, two time periods were measured during RSI:
      spontaneous breathing time (SBT) and apnoea time. RESULTS: We found no
      significant differences between the groups. No periods of desaturation were
      detected. SpO2 was 100% before and after endotracheal intubation in all patients.
      Mean arterial pressure was maintained at a stable level in both groups. Mean SBT
      and apnoea time were 65.6 and 45.8 s in the morbidly obese group, and 70.7 and
      47.7 s in the control group, respectively. CONCLUSION: A combination of
      sevoflurane, propofol, suxamethonium and alfentanil is a suitable method for RSI
      which maintains cardiovascular and respiratory stability in both morbidly obese
      and lean patients.

PMID- 21885983
TI  - A clinical pathway in a post-anaesthesia care unit to reduce length of stay,
      mortality and unplanned intensive care unit admission.
AB  - CONTEXT: The immediate post-operative period is critical with regard to post
      operative outcomes. OBJECTIVE: To assess the impact of a clinical pathway
      implemented in a post-anaesthesia care unit on post-operative outcomes. DESIGN: A
      retrospective cohort study based on electronic patient records. SETTING: A post
      anaesthesia care unit in a Swiss University Hospital. PATIENTS: Adult patients
      after elective and non-elective surgery. INTERVENTION: Implementation of a
      clinical pathway with a nurse-driven fast-track programme for uncomplicated
      patients (systematic use of Aldrete score and systematic discharge without
      physician) and a physician-driven slow-track programme for complicated patients
      (systematic handover between operating theatre and post-anaesthesia care unit,
      and between post-anaesthesia care unit and ward, systematic rounds, systematic
      use of standardised care for post-operative events, strict discharge criteria).
      MAIN OUTCOME MEASURES: Post-anaesthesia care unit length of stay, in-hospital
      mortality and unplanned admission to the ICU after post-anaesthesia care unit
      stay. METHODS: Comparison of the periods before and after implementation using
      median and interquartile range (IQR) and rates (%). STATISTICAL ANALYSIS:
      unpaired Student's t-test, chi test, Wilcoxon rank test. Differences were
      adjusted through multivariate analyses with linear and logistic regression (level
      of significance: P < 0.05) and expressed as odds ratio (OR) with 95% confidence
      interval (95% CI). RESULTS: After implementation, the median post-anaesthesia
      care unit length of stay decreased for all patients from 163 min (IQR 103-291) to
      148 min (IQR 96-270; P < 0.001); in the American Society of Anaesthesiologists 1
      2 patients, it decreased from 152 min (IQR 102-249) to 135 min (IQR 91-227; P <
      0.001). In-hospital mortality decreased for all patients from 1.7 to 0.9%
      [adjusted OR 0.36 (95% CI 0.22-0.59), P < 0.001]. The number of unplanned
      admissions to the ICU decreased from 113 (2.8%) to 91 (2.1%) [adjusted OR 0.73
      (95% CI 0.53-0.99), P = 0.04]. CONCLUSION: A clinical pathway in a post
      anaesthesia care unit can significantly reduce length of stay and can improve
      post-operative outcome.

PMID- 21885985
TI  - Survival of Danish patients with endometrial cancer in the intermediate-risk
      group not given postoperative radiotherapy: the Danish Endometrial Cancer Study
      (DEMCA).
AB  - OBJECTIVES: In a prospective study during the years 1986 to 1988, the Danish
      Endometrial Cancer Group (DEMCA) demonstrated that postoperative radiotherapy was
      unnecessary for low-risk patients with stage I disease. In the present study, we
      evaluated in a population-based study if radiotherapy could also be omitted for
      intermediate-risk patients with stage I disease without loss of survival. STUDY
      DESIGN: From 1998 to 1999, 1166 patients newly diagnosed with carcinoma of the
      uterus were included in this prospective nationwide study. Of these, 232 were
      intermediate-risk patients with stage I disease. All intermediate-risk patients
      received standard primary surgery (hysterectomy, bilateral salpingo-oophorectomy,
      and peritoneal washings), and no postoperative radiotherapy was given. Survival
      analyses were performed using Kaplan-Meier survival estimates. The results were
      compared to the 1986-1988 DEMCA data. RESULTS: The 5-year overall survival (OS)
      rate for the entire population was 77% (stages I-IV). The patients with stage I
      disease were divided into low-, intermediate-, and high-risk; the OS rates were
      91%, 78%, and 62%, and the endometrial cancer-specific survival rates were 97%,
      87%, and 72%, respectively. Using patients' age, tumor grade, myometrial
      invasion, we divided the intermediate-risk group into "high risk" intermediate
      and "low-risk" intermediate with OS rates of 70% and 90% and cancer-specific
      survival of 81% and 96%, respectively. The OS rate (78%) of the intermediate-risk
      group after radiation had been omitted was comparable to the OS rate (79%) of the
      intermediate-risk group in the earlier DEMCA (1986-1988) study where
      postoperative radiation was still the standard of care. CONCLUSION: We conclude
      that in a population-based study, radiotherapy can be omitted for intermediate
      risk patients with stage I endometrial cancer without loss of survival.

PMID- 21885984
TI  - Antiendomysium antibodies assay in the culture medium of intestinal mucosa:  an
      accurate method for celiac disease diagnosis.
AB  - BACKGROUND: Celiac disease (CD) diagnosis is becoming more difficult as patients
      with no intestinal histology lesions may also be suffering from CD. AIM: To
      evaluate the diagnostic accuracy of antiendomysium (EmA) assay in the culture
      medium of intestinal biopsies for CD diagnosis. PATIENTS AND METHODS: The
      clinical charts of 418 patients with CD and 705 non-CD controls who had all
      undergone EmA assay in the culture medium were reviewed. RESULTS: EmA assay in
      the culture medium had a higher sensitivity (98 vs. 80%) and specificity (99 vs.
      95%) than serum EmA/antibodies to tissue transglutaminase (anti-tTG) assay. All
      patients with CD who were tested as false-negatives for serum EmA and/or anti-tTG
      (32 adults and 39 children) carried the human leukocyte antigen alleles
      associated to CD. Furthermore, during the follow-up, four patients with negative
      serum EmA/anti-tTG, normal villi architecture, and positive-EmAs in the culture
      medium, developed villous atrophy and underwent gluten-free diet with consequent
      resolution of the symptoms and complete intestinal histology recovery.
      CONCLUSION: EmA assay in the culture medium should be included in the diagnostic
      criteria for CD diagnosis in 'seronegative' patients.

PMID- 21885987
TI  - The use of auditory prompting systems for increasing independent performance of
      students with autism in employment training.
AB  - In this study a self-operated auditory prompting system is introduced to
      determine if it can increase the on-task behavior for two students with autism
      participating in an employment training program. In addition, the amount of
      prompts provided by support staff is measured. The self-operated auditory
      prompting system consisted of tape recordings of music interspersed with prompts
      of self-evaluation and encouragement related to the job tasks being performed in
      the employment setting. The results of the study indicated a potential positive
      relationship between the self-operated auditory prompting system and the on-task
      behavior of the participants as well as a positive relationship between the
      decreased amounts of prompts used by support staff.

PMID- 21885986
TI  - Redox-active iron-induced oxidative stress in the pathogenesis of clear cell
      carcinoma of the ovary.
AB  - OBJECTIVE: Epithelial ovarian cancer (EOC) is the most lethal pelvic gynecologic
      cancer. Clear cell carcinoma (CCC) and endometrioid adenocarcinoma (EAC) of the
      ovary have been associated with endometriosis, thus indicating that endometriosis
      has been believed to increase the risk of developing EOC. The aim of our review
      was to identify and synthesize the most current information on CCC with regard to
      molecular and pathophysiological distinctions. METHOD: This article reviews the
      English-language literature for molecular, pathogenetic, and pathophysiological
      studies on endometriosis and endometriosis-associated ovarian cancer (EAOC). In
      this review, we focus on the functions and roles of redox-active iron in CCC
      carcinogenesis. RESULTS: The iron-induced reactive oxygen species signals can
      contribute to carcinogenesis via 3 major processes: step 1, by increasing
      oxidative stress, which promotes DNA mutagenesis, histone modification, chromatin
      remodeling, and gene products activation/inactivation thus contributing to EAOC
      initiation; step 2, by activating detoxification and antiapoptotic pathways via
      the transcription factor hepatocyte nuclear factor 1beta overexpression, thereby
      contributing to CCC promotion; and step 3, by creating an environment that
      supports sustained growth, angiogenesis, migration, and invasion of cancer cells
      via estrogen-dependent (EAC) or estrogen-independent (CCC) mechanisms, thus
      supporting tumor progression and metastasis. CONCLUSIONS: These aspects of
      reactive oxygen species biology will be discussed in the context of its
      relationship to EAOC carcinogenesis.

PMID- 21885988
TI  - Requirement for functional BK channels in maintaining oscillation in venomotor
      tone revealed by species differences in expression of the beta1 accessory
      subunits.
AB  - We determined the possible role of large-conductance Ca2+-activated K (BK)
      channels in regulation of venous tone in small capacitance veins and blood
      pressure. In rat mesenteric venous smooth muscle cells (MV SMC), BK channel alpha
      and beta1-subunits were coexpressed, unitary BK currents were detected, and
      single-channel currents were sensitive to voltage and [Ca2+]i. Rat MV SMCs
      displayed Ca sparks and iberiotoxin-sensitive spontaneous transient outward
      currents. Under resting conditions in vitro, rat MV exhibited nifedipine
      sensitive spontaneous oscillatory constrictions. Blockade of BK channels by
      paxilline and Ca2+ sparks by ryanodine constricted rat MV. Nifedipine caused
      venodilation and blocked paxilline-induced, KCl-induced (20 mM), and BayK8644
      induced contraction. Acute inhibition of BK channels with iberiotoxin in vivo
      increased blood pressure and reduced venous capacitance, measured as an increase
      in mean circulatory filling pressure in conscious rats. BK channel alpha-subunits
      and L-type Ca2+ channel alpha1-C subunits are expressed in murine MV. However,
      these channels are not functional because murine MV lack nifedipine-sensitive
      basal tone and rhythmic constrictions. Murine MV were also insensitive to
      paxilline, ryanodine, KCl, and BayK8644, consistent with our previous studies
      showing that murine MV do not have BK beta1-subunits. These data show that not
      only there are species-dependent properties in ion channel control of venomotor
      tone but also BK channels are required for rhythmic oscillations in venous tone.

PMID- 21885989
TI  - A-kinase anchoring protein 9 and IKs channel regulation.
AB  - A-kinase anchoring proteins (AKAPs) create compartmentalized environment inside
      the cell to bring various signaling molecules to their targets. In the heart, a
      slowly activating potassium channel (IKs) important for cardiac repolarization is
      tightly regulated by the sympathetic nervous system in an AKAP-dependent manner.
      IKs channel forms a macromolecular complex with AKAP9 and other enzymes, such as
      protein kinase A, phosphatase, adenylyl cyclase, and phosphodiesterase, all of
      which are responsible to control the phosphorylation state of the channel. Such a
      complex thus ensures the IKs channel to be regulated properly to maintain the
      normal cardiac rhythm. Disruptions of various elements of the complex have been
      found to cause severe pathological consequences, including the long QT syndrome.

PMID- 21885990
TI  - Short-term statin treatment does not prevent ischemia and reperfusion-induced
      endothelial dysfunction in humans.
AB  - Statins are known to have cholesterol-independent pleiotropic effects, such as
      upregulation of the enzyme ecto-5'-nucleotidase. These effects may contribute to
      the protective effect of statins against ischemia and reperfusion (IR).
      Interestingly, pleiotropic effects have been shown to differ between hydrophilic
      and lipophilic statins. Flow-mediated dilation (FMD) represents a largely nitric
      oxide-mediated, endothelium-dependent dilation and has been shown to decrease
      after exposure to IR in humans. FMD has been validated to study (pharmacological)
      interventions in IR injury. We examined the effect of a short-term (3-7 days)
      statin pretreatment on brachial artery endothelial function before and after IR,
      and whether the effect on brachial artery endothelial function differs between
      rosuvastatin (hydrophilic statin) and atorvastatin (lipophilic statin). Our
      results show that IR significantly decreases FMD; however, statin pretreatment
      did not alter the effect of IR on FMD (irrespective of treatment duration or type
      of statin used). This experiment suggests that the cardioprotective effects of
      statins (both lipophilic and hydrophilic) against IR are not mediated through
      preservation of endothelial function.

PMID- 21885991
TI  - Signaling mechanisms mediating uridine adenosine tetraphosphate-induced
      proliferation of human vascular smooth muscle cells.
AB  - Proliferation of vascular smooth muscle cells (SMCs) plays an important role in
      the development of atherosclerosis and restenosis. Extracellular mononucleotides,
      such as adenosine triphosphate and uridine-5'-triphosphate stimulate SMC
      proliferation. However, the effects of dinucleotides on SMC proliferation and
      their underlying signaling mechanisms are less well defined. Recently, increasing
      evidence suggests that the dinucleotide, uridine adenosine tetraphosphate (Up4A)
      plays a role in the regulation of cardiovascular function. We have previously
      demonstrated that Up4A stimulates DNA synthesis and proliferation of human SMCs.
      This study investigated the signaling mechanisms underlying the proliferative
      effect of Up4A. Up4A-induced increase in bromodeoxyuridine incorporation was
      blocked by the mammalian target of rapamycin inhibitor, rapamycin, and the MEK
      inhibitor, PD98059. Up4A-stimulated phosphorylation and kinase activity of S6
      kinase (S6K) and Erk1/2 were inhibited by PD98059, whereas phosphorylation and
      kinase activity of S6K, but not Erk1/2, were inhibited by rapamycin. Up4A also
      increased the phosphorylation of Akt, which was blocked by the PI3-kinase
      inhibitor, LY294002. Up4A-stimulated activation of S6K, but not Erk1/2, was also
      prevented by LY294002. Furthermore, Up4A-stimulated phosphorylation and kinase
      activity of S6K and Erk1/2 were inhibited by the P2 receptor antagonist, suramin,
      but not by the P2X receptor antagonist, Ip5I. Up4A also stimulated an increase in
      the protein expression of cycle-dependent kinase 2, which was prevented by
      rapamycin, PD98059, and suramin. These results suggest that the signaling
      mechanisms underlying the Up4A-stimulated proliferation of SMCs are mediated by
      P2Y receptors and involve the PI3-K/Akt and mitogen-activated protein kinase
      pathways, leading to the independent activation of S6K and an increase in cycle
      dependent kinase 2 expression. This work stresses the concept that dinucleotides,
      like mononucleotides, play potentially important roles in the regulation of
      vascular function.

PMID- 21885992
TI  - Tamoxifen and its metabolites cause acute vasorelaxation of aortic rings by
      inducing vasodilator prostanoid synthesis.
AB  - The vascular effects of tamoxifen (Tam) and its metabolites are poorly known. We
      compared the vasorelaxation induced by Tam and its metabolites (N-desmethyl-Tam,
      4-hydroxy-Tam, and endoxifen) in aortic rings from rats using standardized organ
      bath procedures, and we investigated the mechanisms involved in this effect. Tam
      and its metabolite-induced vasorelaxation in a concentration-dependent manner.
      Although 4-hydroxy-Tam and Tam had similar potency (pD2 = 8.5 +/- 0.1 vs. 8.8 +/-
      0.1, respectively) and maximum effect (Emax = 88.5% +/- 1.3% vs. 92.6% +/- 1.3%,
      respectively), N-desmethyl-Tam and endoxifen were more potent and showed higher
      Emax than Tam did (pD2 = 9.0 +/- 0.1 and 8.9 +/- 0.1; Emax = 101.1% +/- 1.8% and
      101.0% +/- 1.8% for N-desmethyl-Tam and endoxifen, respectively). Although
      preincubation of aortic rings with the estrogen receptor antagonist ICI 182780 or
      with the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester
      hydrochloride induced no changes in the vasorelaxation induced by Tam or 4
      hydroxy-Tam, both drugs significantly reduced Emax in response to N-desmethyl-Tam
      or to endoxifen. Inhibition of cyclooxygenase with indomethacin or the incubation
      with the prostaglandin D2 and E2 receptor antagonist AH6809 reduced the
      vasorelaxation-induced Tam and its metabolites by approximately 50%.
      Preincubation with Nomega-nitro-L-arginine methyl ester hydrochloride combined
      with indomethacin abolished the vasorelaxation-induced Tam and its metabolites.
      These results show that Tam and its metabolites cause acute vasorelaxation by
      inducing vasodilator prostanoids synthesis.

PMID- 21885993
TI  - Development of angiotensin II-induced abdominal aortic aneurysms is independent
      of catalase in mice.
AB  - Chronic infusion of angiotensin II (AngII) into mice augments the development of
      abdominal aortic aneurysms (AAAs). Catalase is an important antioxidant enzyme in
      cellular peroxisome, and it physiologically maintains tissue and cellular redox
      homeostasis and thus plays a central role in defense against oxidative stress.
      The purpose of this study was to define whether deficiency of catalase influences
      AngII-induced AAAs. Male acatalasemic (C3H/AnLCsCs) mice and wild-type
      (C3H/AnLCsCs) mice (8-12 weeks old, N = 24 and 25, respectively) were fed a
      normal chow for 5 weeks. After 1 week of acclimtion, mice were infused
      subcutaneously with AngII (1000 ng.kg.min) by osmotic minipumps for 4 weeks.
      AngII increased systolic blood pressure equivalently in both groups. Acatalasemia
      had no effect on serum cholesterol concentrations. The body weight of
      acatalasemic mice was slightly greater than that of wild-type mice (P = 0.008).
      Although aortic catalase activity in acatalasemic mice was significantly low (P <
      0.001), acatalasemia had no significant effect on the incidence of AngII-induced
      AAA formation (acatalasemia, 23%; wild, 21%), ex vivo measurement of maximal
      diameter of abdominal aorta (acatalasemia, 1.22 +/- 0.29 mm; wild, 1.21 +/- 0.17
      mm), or aortic deposition of lipid peroxidation products such as 4-hydroxy-2
      nonenal. The development of AngII-induced AAAs is independent of catalase.

PMID- 21885994
TI  - Metoprolol ameliorates cyclosporine a-induced hypertension and nephrotoxicity in
      rats.
AB  - Despite their clinical relevance as important cardiovascular modulators, there
      are few studies regarding the potential protective effect of beta-blockers
      against immunosuppressive-induced cardiovascular side effects. This study
      investigated the possible ameliorating effect of beta1-blocker, metoprolol (MTP),
      against both hypertensive and nephrotoxic effects of cyclosporine A (CSA).
      Compared with vehicle (olive oil)-treated rats, chronic treatment with CSA (20
      mg.kg.d subcutaneous, for 14 days) increased systolic blood pressure, elevated
      renal function indices and plasma renin activity, impaired renovascular
      responsiveness of isolated perfused rat kidneys to endothelium-dependent
      vasodilations induced by carbachol. These effects were abolished upon concurrent
      administration of MTP (5 mg.kg.d for 14 days, intraperitoneal). The possibility
      that alterations in the antioxidant and/or circulating cytokine levels
      contributed to the CSA-MTP interaction was also investigated. MTP abrogated the
      oxidative (superoxide dismutase, catalase), lipid peroxidation (malondialdyde),
      and elevated the cytokine (TNF-alpha and TGF-beta) effects of CSA.
      Histologically, CSA caused tubular brush border loss and isometric vacuolization
      clustered in the proximal tubule; this effect disappeared in rats cotreated with
      MTP. The use of a nonhypotensive dose of MTP (1.25 mg/kg) countered in part
      endothelium dysfunction altered oxidative stress parameters and cytokine levels
      in CSA-treated rats. Collectively, MTP abrogates both the hypertensive and the
      nephrotoxic effects of CSA via ameliorating endothelium dysfunction, oxidative
      stress, and upregulated cytokine levels caused by CSA. The demonstration of
      nephroprotection by the low dose of MTP suggests that its renal effect may be
      partially unrelated to its hemodynamic activity.

PMID- 21885996
TI  - Understanding the concept of medialization in scapula fractures.
AB  - OBJECTIVE: To determine whether medial displacement of the glenoid with respect
      to the midline occurs in scapula fractures and the potential impact on fracture
      reduction technique. DESIGN: Retrospective case series. SETTING: Level I trauma
      medical center. PATIENTS: Seventy patients who sustained scapula fractures from
      2004 to 2008 and a comparison group of 47 normal patients without scapula
      fractures. INTERVENTION: Computed tomography scans were analyzed from all 70
      patients who sustained scapula fractures. Measurements were obtained from the
      most lateral aspect of the glenoid articular surface to the midline (vertebral
      spinous process) on both the injured and non-injured sides to assess medial or
      lateral displacement of the glenoid with respect to the midline. The same
      measurements were obtained bilaterally for the 47 patients in the comparison
      group. MAIN OUTCOME MEASUREMENT: Medial or lateral displacement of the glenoid
      with respect to the midline. RESULTS: Our results showed that for all 70 patients
      with scapula fractures, the average distance from the glenoid articular surface
      to the midline was 6.0 mm +/- 10.1 greater for the injured shoulder than for the
      non-injured side (P = 0.0017), indicating lateral displacement of the glenoid. In
      the comparison group, the mean right-to-left difference from midline was -0.9 mm
      +/- 9.2 (P = 0.4399). CONCLUSION: Our analysis demonstrates that in this group of
      patients with scapula fractures, there was slight lateral displacement of the
      glenoid with respect to the midline with significant variability in the degree of
      medial/lateral displacement. This finding provides evidence that the glenoid
      fragment retains its anatomic position, and the proximal scapula body fragment
      may be the fracture component that lateralizes. Recognizing this pattern of
      displacement may enhance our understanding of scapula fractures and the
      techniques used during open reduction and internal fixation.

PMID- 21885997
TI  - The medical orthopaedic trauma service:  an innovative multidisciplinary team
      model that decreases in-hospital complications in patients with hip fractures.
AB  - OBJECTIVES: The purpose of the study is to evaluate the influence of a
      multidisciplinary model of care on the incidence of postoperative complications
      after a hip fracture. DESIGN: Retrospective cohort series. SETTING: Level I
      trauma center. PATIENTS/PARTICIPANTS: Three hundred six patients with
      pertrochanteric femur fracture (OTA classification: 31-B1, 31-B2, 31-B3, 31-A1,
      31-A2, 31-B3, 32-A1, and 32-A2). INTERVENTION: A multidisciplinary, collaborative
      model of perioperative care: the Medical Orthopaedic Trauma Service (MOTS). MAIN
      OUTCOME MEASURES: Incidence of in-patient complications, length of in-patient
      hospitalization, readmission rate after hospital discharge, and postdischarge
      mortality at 90 days and 1 year. RESULTS: Although there was no change in length
      of hospitalization, there was a significantly decreased overall incidence of in
      patient complications and a decreased incidences of new-onset urinary tract
      infection and arrhythmias in the MOTS cohort. These differences persisted after
      controlling for age, comorbidity, gender, ethnicity, type of fracture, and number
      of days from admission to surgery with a logistic regression model. Subgroup
      analysis of patients with an American Society of Anesthesiologists physical
      status classification of 1 or 2 revealed a significantly decreased 90 day
      readmission rate with the MOTS model, but this did not persist in a regression
      model (P = 0.07). CONCLUSIONS: A multidisciplinary, collaborative model of care
      for patients with hip fractures decreases the incidence of postoperative in
      patient complications and may influence hospital readmission rates. LEVEL OF
      EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete
      description of levels of evidence.

PMID- 21885998
TI  - Return to duty after type III open tibia fracture.
AB  - INTRODUCTION: Despite the high incidence of battlefield orthopaedic injuries,
      long-term outcomes and return to duty (RTD) status have rarely been studied. Our
      purpose was to determine the RTD rate for soldiers who sustained Type III open
      tibia fractures in active combat. METHODS: One hundred fifteen soldiers who
      sustained battle-related Type III open tibia fractures were retrospectively
      reviewed. The Army Physical Evaluation Board database was reviewed to determine
      which soldiers were able to RTD and the disability ratings of those not able to
      RTD. RESULTS: The overall RTD rate was 18%, isolated open fractures had a RTD
      rate of 22%, salvaged extremities had a RTD rate of 20.5%, and amputees had a RTD
      rate of 12.5%. Older age and higher rank were both significant factors in
      increasing the likelihood of RTD and amputees had significantly higher disability
      ratings than those with salvaged extremities. CONCLUSION: Despite the severe
      nature of combat extremity wounds, 20% of patients with salvaged Type III open
      tibia fractures and 22% with isolated injuries were able to return to active
      duty. These rates are similar to those reported for civilian amputees. Amputees
      in our cohort were less likely to RTD.

PMID- 21885999
TI  - A comparison of the Gallie technique and casting versus the harms technique for
      the treatment of odontoid fractures.
AB  - OBJECTIVE: The objective of this study was to compare perioperative, clinical
      parameters, complications, and reoperation rate of the Gallie technique and head
      neck-chest plaster with the Harms technique in the treatment of odontoid
      fractures. DESIGN: A retrospective study. SETTING: Level I spine center.
      PATIENTS: Fifty-seven patients with odontoid fractures treated either with the
      Gallie technique and casting or the Harms technique between July 2002 and June
      2008. INTERVENTION: Surgery. MAIN OUTCOME MEASUREMENTS: At a minimum of 2-year
      follow-up, comparison of the two groups was conducted in terms of hospital stay,
      blood loss, operation time, cost of the first admission, total cost, time to
      fusion, time to return to previous occupation, Japanese Orthopedic Association
      scores, visual analog scale scores of neck pain, complications (nonunion, delayed
      union, hardware breakage, wound infection), and reoperation rate. RESULTS: There
      were no significant differences in terms of hospital stay, time to fusion,
      Japanese Orthopedic Association scores, neck pain visual analog scale scores,
      complications, or reoperation rate between the two groups. Blood loss, operation
      time, cost of the first admission, and total cost were significantly lower in the
      Gallie group than that in the Harms group. However, the Gallie group took longer
      to return to previous occupation than the Harms group (P < 0.001). CONCLUSIONS:
      Management of odontoid fractures by either the Gallie technique and casting or
      the Harms technique was found to be similar in clinical outcomes. Although the
      Harms technique was associated with more blood loss, operation time, and cost,
      the Harms technique was found to be superior to the Gallie technique with casting
      in terms of time to return to previous occupation.

PMID- 21886000
TI  - Knee pain correlates with union after tibial nailing.
AB  - OBJECTIVES: The purpose of this study is to evaluate the change in quantitatively
      scored knee pain during union. DESIGN: This is a retrospective review of
      prospectively collected data over a 15-year period. SETTING: Academic medical
      center. PATIENTS: All patients treated with an intramedullary nail were evaluated
      for knee pain and union. Four hundred twenty-eight patients with 443 tibia
      fractures were included. INTERVENTION: All tibia fractures were treated with an
      intramedullary nail. OUTCOMES: Patient-based knee pain was scored from 0 to 3.
      Fracture union was also graded using a modified Hammer score based on cortical
      bridging and remodeling. RESULTS: We found a significant inverse association
      between pain and union score (P < 0.01). In contradistinction, there was not a
      correlation between time from surgery and pain (P = 0.13). Because union score
      and time were related, a model was created with both parameters. This model
      demonstrated a statistical correlation with union score (P < 0.01), but not for
      time from surgery (P = 0.18). CONCLUSIONS: We postulated that knee pain may
      correlate with either union or time from surgery. We found a statistically
      significant, negative correlation between knee pain and fracture union. There was
      no such association between pain and time from surgery.

PMID- 21886001
TI  - The impact of smoking on complications after operatively treated ankle fractures-
      a follow-up study of 906 patients.
AB  - OBJECTIVES: This study on patients with operatively treated ankle fractures aimed
      to investigate the impact of smoking on postoperative complications and
      especially deep wound infections. DESIGN: Cohort study with prospective follow
      up. SETTING: University-associated teaching hospital with advanced trauma care.
      PATIENTS: A consecutive series of patients (n = 906) operatively treated for an
      acute ankle fracture during a 3-year period was identified. For the analysis, the
      patients were categorized as nonsmokers (n = 721) and smokers (n = 185). Data
      were collected from the department database and completed with a review of the
      patients' medical charts. MAIN OUTCOME MEASURES: Postoperative complications.
      RESULTS: Follow-up data at 6 weeks were available for 98.2% of the patients.
      Postoperative complications of any kind (30.1% versus 20.3%, P = 0.005) as well
      as deep wound infections (4.9% versus 0.8%, P < 0.001) were more common among
      smokers than nonsmokers. Multivariable analyses showed that smokers had six times
      higher odds of developing a deep infection compared with nonsmokers. A more
      complicated fracture, associated diabetes mellitus, and unsatisfactory operative
      fracture reduction also enhanced the risk of postoperative complications.
      CONCLUSIONS: We conclude that cigarette smoking increases the risk of
      postoperative complications in patients operatively treated for an ankle
      fracture. Smoking is a considerable risk factor. Therefore, physicians, nurses,
      and other healthcare professionals should strive to support patients to stop
      smoking while still under acute treatment.

PMID- 21886002
TI  - Results of cephallomedullary nail fixation for displaced intracapsular femoral
      neck fractures.
AB  - OBJECTIVE: To evaluate the outcomes of displaced intracapsular femoral neck
      fractures treated with a cephalomedullary device. DESIGN: Retrospective study.
      SETTING: Level I trauma center. PATIENTS: Between 2002 and 2008, 18 patients with
      displaced intracapsular femoral neck fractures were treated at our Level I trauma
      center with a cephalomedullary nail. There were 12 males and six females. Six
      patients were younger than 60 years of age with a mean age of 63 years (range, 40
      88 years). Thirteen fractures were midcervical (Orthopaedic Trauma Association
      [OTA] 31-B2.2 and B2.3), and five fractures were subcapital (OTA 31-B3). Patients
      with basicervical fractures (OTA 31-B2.1) and nondisplaced subcapital fractures
      (OTA 31-B1) were excluded. INTERVENTION: All patients underwent cephalomedullary
      nail fixation of their femoral neck fractures under the supervision of fellowship
      trained orthopaedic trauma surgeons. MAIN OUTCOME MEASUREMENTS: Postoperative
      radiographs were evaluated for fracture reduction quality. Clinical follow-up was
      available on 13 patients with a minimum of 12 months (range, 12-25 months). A
      radiographic and chart review was done to identify complications and outcomes.
      RESULTS: Seven of eight fractures that healed were anatomically reduced. No
      failures occurred in the six patients younger than 60 years. Fixation failed in
      five of 13 fractures (38.4%) with varus collapse as the typical failure mode. The
      mean time to failure in these cases was 3.8 months (range, 1-7 months). Overall,
      the failure rate for the subcapital fractures was 100% (three of three) and for
      midcervical 20% (two of 10) with all failures being in patients older than 60
      years (71.4%). Osteonecrosis without fixation failure or cutout occurred in one
      case. CONCLUSION: Cephalomedullary nail fixation of displaced intracapsular
      femoral neck fractures demonstrated mixed results. For younger patients with
      midcervical fractures that were well reduced, the fixation performed well.
      Displaced subcapital fractures in patients older than 60 years demonstrated a
      100% failure rate. As a result, we cannot advocate cephalomedullary fixation for
      displaced intracapsular femoral neck fractures in patients older than 60 years,
      although in younger patients, these implants may provide an alternative to side
      plate based fixation devices.

PMID- 21886003
TI  - Ideal tibial intramedullary nail insertion point varies with tibial rotation.
AB  - OBJECTIVES: The aim of the study was to investigate how superior entry point
      varies with tibial rotation and to identify landmarks that can be used to
      identify suitable radiographs for successful intramedullary nail insertion.
      METHODS: The proximal tibia and knee were imaged for 12 cadaveric limbs
      undergoing 5 degrees  increments of internal and external rotation. Medial and
      lateral arthrotomies were performed, the ideal superior entry point was
      identified, and a 2-mm Kirschner wire inserted. A second Kirschner wire was
      sequentially placed at the 5-mm and then the 10-mm position, both medial and
      lateral to the initial Kirschner wire. Radiographs of the knee were obtained for
      all increments. The changing position of the ideal nail insertion point was
      recorded. RESULTS: A 30 degrees  arc (range, 25 degrees -40 degrees ) provided a
      suitable anteroposterior radiograph. On the neutral anteroposterior radiograph,
      the Kirschner wire was 54% +/- 1.5% (range, 51-56%) from the medial edge of the
      tibial plateau. For every 5 degrees  of rotation, the Kirschner wire moved 3% of
      the plateau width. During external rotation, a misleading medial entry point was
      obtained. A fibular bisector line correlated with an entry point that was ideal
      or up to 5 mm lateral to this but never medial. The film that best showed the
      fibular bisector line was between 0 degrees  and 10 degrees  of internal rotation
      of the tibia. CONCLUSIONS: The fibula head bisector line can be used to avoid
      choosing external rotation views and, thus, avoid medial insertion points. The
      current results may help the surgeon prevent malalignment during intramedullary
      nailing in proximal tibial fractures.

PMID- 21886005
TI  - Anatomic relationships after instrumentation of the midshaft clavicle with 3.5-mm
      reconstruction plating: an anatomic study.
AB  - OBJECTIVES: To examine the anatomic relationships of the major neurovascular
      structures at the midshaft clavicle region as they pertain to plate
      osteosynthesis in the treatment of midshaft clavicle fractures. METHODS: Fifteen
      fresh cadaveric specimens were dissected at the clavicle region. The shortest
      distances from the midshaft clavicular fracture lines to the subclavian artery
      and vein and brachial plexus were measured with a digital caliper with the limb
      in anatomic position and at 90 degrees  of abduction. The mean and range distance
      values were recorded. The clavicles were then instrumented with eight-hole, 3.5
      mm reconstruction plates and screws (Synthes, Paoli PA) placed in superior and
      anteroinferior positions. The shortest distances from the screw tips to the
      neurovascular structures were measured at variable plate positions, fracture
      zones, and limb positions. The incidence of screw tip contact was reported.
      RESULTS: In 20% (three of 15) of the specimens, screw tip contact with a major
      neurovascular structure occurred. In these three specimens, two screw tip
      contacts occurred with the plate in a superior position and two occurred with the
      plate in an anteroinferior position. In one specimen, screw tip contact occurred
      with both plate positions. Limb abduction to 90 degrees  consistently increased
      the distance of the neurovascular structures from the clavicle. There was no
      observable trend in screw contact frequency in respect to limb position or
      fracture zone. CONCLUSION: Caution must be exercised when instrumenting midshaft
      clavicle fractures regardless of chosen plate position. Limb abduction to 90
      degrees  provides an added measure of safety during clavicle instrumentation.

PMID- 21886006
TI  - Functional and quality-of-life results of displaced and nondisplaced proximal
      humeral fractures treated conservatively.
AB  - OBJECTIVES: Functional and quality-of-life outcomes of conservatively treated
      proximal humeral fractures. DESIGN: Prospective study. SETTING: University
      orthopedic department at a hospital. PATIENTS/PARTICIPANTS: Seventy consecutive
      patients between the ages of 60 and 85 years. INTERVENTION: Conservative
      treatment. MAIN OUTCOME MEASUREMENTS: Functional outcome measured according to
      the Constant score, quality of life assessed using EuroQol-5D, and fracture
      pattern analyzed with x-ray and computed tomography scan. RESULTS: : All
      fractures consolidated uneventfully with no loss of reduction in either group.
      Four-part fractures obtained the worst functional results (33.66) followed by
      three-part fractures (54.64) and finally two-part fractures (65.88 and 71). Mild
      pain was expected in three- and four-part fractures, whereas two-part fractures
      achieved near complete pain relief. Nondisplaced fractures obtained a final
      Constant score of 73.58 and displaced fractures a score of 59.41 with significant
      differences in all Constant score items with the exception of external rotation.
      Although patients older than 75 years scored lower (54.63) than those younger
      than 75 years (70.83), there was no difference in the quality-of-life perception.
      CONCLUSION: Conservative treatment of proximal humeral fractures in those
      patients older than age 75 years provides good pain relief with limited
      functional outcome. Despite limited functional outcome, this appears to have no
      effect on the quality-of-life perception in the population studied. Four-part
      fractures present the worst results and treatment options may need to be
      discussed with the patient to adjust treatment to patient expectations.

PMID- 21886007
TI  - Pediatric end-stage liver disease score in acute liver failure to assess poor
      prognosis.
AB  - BACKGROUND AND AIM: Although establishing accurate prognosis in acute liver
      failure (ALF) is of paramount importance, prognostic scoring systems still fail
      to achieve success. The pediatric end-stage liver disease (PELD) score has been
      used as a predictor of mortality in children with chronic liver disease listed
      for liver transplantation (LT); however, experience with the PELD score in ALF is
      limited. The goal of the present study was to investigate the prognostic accuracy
      of the PELD score in children with ALF. PATIENTS AND METHODS: PELD score was
      calculated based on results of blood tests obtained at hospital admission from
      June 1999 to January 2009, in 40 consecutive patients younger than 18 years who
      presented with ALF. Poor outcome was defined as LT or death. RESULTS: Mean (+/
      SD) age of patients was 5.3 +/- 4.4 years (range 6 months-17 years); 52.5% were
      girls (n = 21). Etiologies of ALF were hepatitis A in 42.5% (17), indeterminate
      in 35% (14), autoimmune hepatitis in 17.5% (type 1 12.5% [n5], type 2 5% [n2]),
      and toxic in 5% (2). Mean PELD score was 34.92 +/- 10.48 (range 6-55). PELD
      scores obtained on admission were significantly higher among nonsurvivors (39.8
      +/- 9.5) and recipients of an LT (39 +/- 7.1) compared with those who survived
      without LT (31.3 +/- 3) (P < 0.001). A cutoff of 33 in PELD score using receiver
      operating characteristic curves showed 81% specificity and 86% sensitivity for
      poor outcome (positive predictive value 92% and negative predictive value 69%;
      area under curve 0.88 95% confidence interval 0.77-1.0; P < 0.0001). CONCLUSIONS:
      PELD score obtained upon admission may be of help to establish the optimal timing
      for LT evaluation and listing. Further validation in larger and more diverse
      populations is needed.

PMID- 21886008
TI  - Glyceroluria and neonatal hemochromatosis.

PMID- 21886009
TI  - Anterior cruciate ligament recostruction with bone-patellar tendon-bone autograft
      in Tanner 3 stage patients with open physes.
AB  - Ten skeletally immature patients were treated with an arthroscopic-assisted
      anterior cruciate ligament reconstruction with bone-patellar tendon bone
      autograft (compass, 50-55 degrees ; holes, 7-9 mm). Radiological assessments
      (standard radiograph), Orthopadische Arbeitsgruppe Knie (OAK) score and KT 1000,
      were conducted on all patients, 1 year after surgery. Skeletal maturity had been
      reached by all patients and no complications were observed. All patients returned
      to their preinjury sport level. Drilling more vertical tunnels when bone-tendon
      bone autograft was chosen to avoid partial epiphysiodesis and offers good
      functional and isometric results.

PMID- 21886010
TI  - Positional physical characteristics of players drafted into the National Football
      League.
AB  - To investigate the positional physical requirements necessary to be drafted into
      the National Football League (NFL), data from the annual NFL combine over the
      years 2005-2009 were examined. Only those players invited to the combine and
      subsequently drafted in the same year (n = 1,136) were included in the study.
      Data from 8 combine physical performance tests were examined for 15 positions.
      Combine measures evaluated for the center, cornerback, defensive end, defensive
      tackle, free safety, fullback, inside linebacker, offensive guard, offensive
      tackle, outside linebacker, quarterback, running back, strong safety, tight end,
      and wide receiver positions were the 9.1-, 18.3-, and 36.6-m sprints, the
      vertical and broad jumps, the 18.3-m shuttle run, the 3-cone drill, and the 102.1
      kg bench press for maximum repetitions and, from this, a predicted measure of 1
      repetition maximum. A 1-way analysis of variance detected differences in all 9
      performance measures (p < 0.01). Post hoc independent t-tests indicated that over
      most tests many positions exhibited outcomes significantly different from most
      other positions. Generally, lineman positions performed inferiorly in sprint,
      jump and change-of-direction ability measures and superiorly in the upper body
      strength measures. Conversely, defensive back positions were the worst performers
      in the upper body strength test, and wide receivers and defensive backs were the
      best performers in all other measures. In general, offensive and defensive
      positions that commonly compete directly against one another display similar
      physical characteristics. Any advantages (statistically significant and not)
      between positions in direct competition were consistently in favor of defensive
      positions. The results of the present research present position-specific profiles
      for each of 15 positions. Coaches and practitioners will be able to use the
      findings of this research to better prepare athletes for entry into the NFL.

PMID- 21886011
TI  - A comparison of cutting technique performance in rugby union players.
AB  - Rugby union is a dynamic running game requiring players to regularly perform
      change of direction maneuvers to avoid player opposition. The change of
      direction/cutting task is characterized by rapid deceleration onto the plant leg
      (PL) then reacceleration by the push-off leg (POL) into the new direction.
      Identification of the kinematic characteristics of cutting tasks and their
      relationship to playing ability may offer practical guidelines for coaches and
      strength and conditioning staff to design effective agility drills and provide
      player feedback to improve technique. Therefore, the purpose of this study was to
      investigate the kinematic and temporal characteristics of cutting tasks and their
      relationship to performance in rugby union players. Semiprofessional rugby union
      players from the All-Ireland League were placed in a Starters (N = 13) or
      Nonstarters (N = 10) group based on whether they were routinely selected in the
      starting team or were reserve 'bench' players. Each participant was fitted with
      reflective markers and performed 10 cutting trials (5 left, 5 right) of a single
      45 degrees  cutting task to collect relevant kinematic data. The directions of
      the cutting trials were classified as a dominant or nondominant cut based on the
      participant's dominant leg. All trials were then analyzed to determine the
      timings, angular displacements, and velocities during key events of the PL and
      POL in the cutting task. The total time to complete the cutting task was not
      statistically significant between groups; however, Starters demonstrated
      significantly shorter contact time of the PL during dominant cuts and initiated
      knee extension of the POL faster than Nonstarters in dominant and nondominant
      cuts. This preliminary study demonstrates that components of the cutting task
      differed between groups and may provide an insight for strength and conditioning
      professionals to assess change of direction technique.

PMID- 21886012
TI  - Effects of deception on exercise performance:  implications for determinants of
      fatigue in humans.
AB  - PURPOSE: The aim of this study was to investigate whether it was possible to
      reduce the time taken to complete a 4000-m cycling time trial by misleading
      participants into believing they were racing against a previous trial, when, in
      fact, the power output was 2% greater. METHODS: Nine trained male cyclists each
      completed four 4000-m time trials. The first trial was a habituation and the data
      from the second trial was used to form a baseline (BL). During trials 3 and 4,
      participants raced against an avatar, which they were informed represented their
      BL performance. However, whereas one of these trials was an accurate (ACC)
      representation of BL, the power output in the other trial was set at 102% of BL
      and formed the deception condition (DEC). Oxygen uptake and RER were measured
      continuously and used to determine aerobic and anaerobic contributions to power
      output. RESULTS: There was a significant difference between trials for time to
      completion (F = 15.3, P = 0.00). Participants completed DEC more quickly than BL
      (90% CI = 2.1-10.1 s) and ACC (90% CI = 1.5-5.4 s) and completed ACC more quickly
      than BL (90% CI = 0.5-4.8 s). The difference in performance between DEC and ACC
      was attributable to a greater anaerobic contribution to power output at 90% of
      the total distance (F = 5.3, P = 0.02, 90% CI = 4-37 W). CONCLUSIONS: The
      provision of surreptitiously augmented feedback derived from a previous
      performance reduces time taken for cyclists to accomplish a time trial of known
      duration. This suggests that cyclists operate with a metabolic reserve even
      during maximal time trials and that this reserve can be accessed after deception.

PMID- 21886014
TI  - Can 18F-fluorodeoxyglucose positron emission tomography predict responses to
      neoadjuvant therapy in oesophageal cancer patients? A meta-analysis.
AB  - OBJECTIVES: Neoadjuvant therapy for the treatment of oesophageal cancer was
      introduced in an effort to improve prognosis. Response assessment is crucial for
      the treatment of patients with oesophageal cancer. Currently, 18F
      fluorodeoxyglucose positron emission tomography (18F-FDG PET) seems to be the
      best available tool to assess neoadjuvant therapy response in patients with
      oesophageal cancer. The purpose of this study was to assess the diagnostic value
      of 18F-FDG PET for the evaluation of neoadjuvant therapy responses in patients
      with oesophageal cancer using a meta-analysis. A unified procedure and evaluation
      standard for 18F-FDG PET in the assessment of neoadjuvant therapy response should
      be established. METHODS: All published English-language studies pertaining to the
      assessment of neoadjuvant therapy response in patients with oesophageal cancer
      using 18F-FDG PET in the MEDLINE and EMBASE databases were collected. The
      methodological quality of the included studies was evaluated according to the
      Quality Assessment of Diagnostic Accuracy Studies quality assessment tool. Pooled
      sensitivity, specificity, diagnostic odds ratios and summary receiver operating
      characteristic curves were obtained using statistical software. RESULTS: Thirteen
      studies included in the meta-analysis fulfilled the inclusion criteria of the
      Quality Assessment of Diagnostic Accuracy Studies quality assessment tool. The
      pooled sensitivity, specificity and diagnostic odds ratios for F-18FDG PET in the
      evaluation of neoadjuvant therapy response in patients with oesophageal cancer
      were 70.3% [95% confidence interval (CI): 64.4-75.8], 70.1% (95% CI: 65.1-74.8)
      and 9.389 (95% CI: 3.482-25.319), respectively. The area under the curve and the
      Q value for the summary receiver operating characteristic curve were 0.8244 and
      0.7575, respectively. CONCLUSION: 18F-FDG PET has some value in the assessment of
      neoadjuvant therapy response in patients with oesophageal cancer. A 50% reduction
      in standardized uptake value between pretherapy and posttherapy positron emission
      tomography scans performed in the first 2 weeks after the initiation of
      neoadjuvant therapy is the optimal condition for predicting a response to
      neoadjuvant therapy in patients with oesophageal cancer.

PMID- 21886013
TI  - Association between an increment of 30-minute postchallenge plasma glucose and
      urine albumin excretion exists in postmenopausal women but not in premenopausal
      women.
AB  - OBJECTIVE: Usually, the increment of 30-minute postchallenge plasma glucose
      (DeltaG30-0) represents the highest glucose spike in the population with normal
      glucose regulation (NGR). The aim of this study was to explore the differences in
      DeltaG30-0 and urinary albumin excretion, a marker for widespread vascular
      damage, between premenopausal and postmenopausal women, and the relationship
      between DeltaG30-0 and urinary albumin excretion. METHODS: A population-based
      cross-sectional study, consisting of 5,289 participants aged 20 to 75 years from
      six different communities, was conducted in Shanghai between 2007 and 2008. We
      assessed postchallenge blood glucose and insulin at 0-, 30-, and 120-minute
      urinary albumin and creatinine. DeltaG30-0 was calculated as 30-minute
      postchallenge glucose minus fasting plasma glucose, and the albumin-to-creatinine
      ratio (ACR) was used to reflect urinary albumin excretion. Among these, the data
      of 2,240 women with NGR were analyzed. RESULTS: (1) Postmenopausal women had
      higher DeltaG30-0 and ACR than did premenopausal women (3.55 +/- 1.52 mmol/L vs
      3.21 +/- 1.49 mmol/L and 6.92 [4.91-10.99] mg/g vs 6.18 [4.17-10.07] mg/g,
      respectively; all P < 0.001). (2) Multivariable logistic regression showed that
      DeltaG30-0 was independently associated with increased ACR in postmenopausal
      women with NGR (odds ratio, 1.10; P = 0.048) but not in premenopausal women. (3)
      The main factor associated with DeltaG30-0 was the early-phase glucose
      disposition index drawn from the multivariable linear regression, which explained
      approximately 19% and 28% of the variation of DeltaG30-0 in premenopausal and
      postmenopausal women, respectively (both P < 0.001). CONCLUSIONS: In the NGR
      population, postmenopausal women have higher DeltaG30-0 and ACR compared with
      premenopausal women. The relationship between DeltaG30-0 and increased urine
      albumin excretion existed in postmenopausal women.

PMID- 21886015
TI  - Cytochrome P450 CYP2B6 genotypes and haplotypes in a Colombian population: 
      identification of novel variant CYP2B6 alleles.
AB  - OBJECTIVE: Information on CYP2B6 allele frequencies and detrimental genotypes in
      mixed human populations is scarce. The aim of this study was to analyze the
      frequencies and haplotypes of nonsynonymous CYP2B6 single nucleotide
      polymorphisms (SNPs) in a Colombian population. METHODS: One hundred and fifty
      two healthy individuals were analyzed for five nonsynonymous CYP2B6 SNPs, namely
      rs8192709, rs3745274, rs2279343 rs28399499, and rs3211371. RESULTS: Besides eight
      known variant alleles, we identified two as yet unknown variant alleles
      combining, respectively, the SNPs rs3745274 and rs3211371 and rs8192709 and
      rs3745274. Comparison of Colombian mestizo individuals with other mestizo
      population indicates statistically significant differences (P<0.001) for the gain
      of-function CYP2B6*4 allele and for combined detrimental CYP2B6 alleles. In
      addition, we observed a low linkage between the SNPs rs3745274 and rs2279343,
      which are often assumed as linked. CONCLUSION: In conclusion, large interethnic
      and intraethnic variability exists for CYP2B6 polymorphisms, thus reinforcing the
      need for tailored genotyping protocols for CYP2B6 testing as a biomarker of drug
      response.

PMID- 21886016
TI  - Lower tacrolimus daily dose requirements and acute rejection rates in the CYP3A5
      nonexpressers than expressers.
AB  - BACKGROUND: CYP3A5 genetic polymorphisms contribute to marked interindividual
      differences in the metabolism of and response to tacrolimus in humans. OBJECTIVE:
      This study was aimed to clarify the impact of the CYP3A5*3 variant on tacrolimus
      dose requirements and acute rejection rates in patients with organ
      transplantation. METHODS: A literature search was performed up to August 2009 by
      using the Cochrane library, PubMed, Medline, and EMBase. RESULTS: Twenty-three
      studies (a total of 1779 patients) were included in this meta-analysis. Eighteen
      studies (1443 patients) were involved in renal transplantation and five studies
      (336 patients) in liver transplantation. Results of meta-analysis demonstrated
      that, in renal transplant patients, despite the presence of significant
      heterogeneity, CYP3A5 expressers required higher mean tacrolimus daily doses by
      0.045 mg/kg (95% confidence interval (CI), 0.033-0.056) than nonexpressers.
      Furthermore, sub-analysis of the time of posttransplantation showed that CYP3A5
      expressers required higher daily doses than nonexpressers by 0.010, 0.084, 0.041,
      0.037, and 0.044 mg/kg at week 2, and at month 1, 3, 6, and 12, respectively.
      Subset analysis of the ethnicity of organ recipients indicated that mean
      tacrolimus daily doses were 0.056, 0.037, and 0.077 mg/kg higher in CYP3A5
      expressers than non- expressers for white, Chinese, and Japanese patients,
      respectively. In contrast, for liver transplant patients, higher tacrolimus daily
      doses were required not only in CYP3A5 expressers of the organ donors than
      nonexpressers by 0.024 mg/kg (95% CI, 0.019-0.028), but also in CYP3A5 expresser
      of the organ recipients than nonexpresser by 0.012 mg/kg (95% CI, 0.005-0.018).
      However, a significant difference in the acute organ rejection rate was observed
      only at one month (odds ratio, 3.27; 95% CI, 1.57-6.81; P=0.002). CONCLUSION:
      Tacrolimus daily dose requirements may vary with the presence of the CYP3A5*3
      variant, ethnicity of the organ recipients, and the time of posttransplantation.
      In addition, the acute organ rejection rate may be higher in CYP3A5 expressers
      than nonexpressers over the first month after transplantation.

PMID- 21886017
TI  - Focal navigated laser photocoagulation in retinovascular disease: clinical
      results in initial case series.
AB  - PURPOSE: To evaluate clinical results after the use of a novel integrated imaging
      and laser device to perform focal retinal navigated laser photocoagulation in
      perifoveal abnormalities and retinovascular disease. METHODS: Interventional case
      series of 25 consecutive eyes with perifoveal and retinovascular diseases treated
      with a navigated laser photocoagulator Navilas (OD-OS, Berlin, Germany). We
      treated eyes with perifoveal telangiectasia (n = 3), central serous
      chorioretinopathy (n = 2), and diabetic macular edema with focal leakage (n =
      20). RESULTS: The treatments were performed without a contact lens and without
      topical anesthesia. There was no inadvertent photocoagulation of the fovea, and
      all laser applications accurately hit the preplanned points. Mean and median (+/-
      standard deviation) foveal thickness at baseline was 535 +/- 171 MUm and 402 +/-
      152 MUm, respectively. Mean and median (+/- standard deviation) foveal thickness
      at 6 months was 318 +/- 112 MUm and 221 +/- 127 MUm, respectively. This
      represents a statistically significant decrease in foveal thickness (P = 0.003).
      Mean and median visual acuity at baseline was 20/80 and 20/50, respectively. Mean
      and median visual acuity at 6 months was 20/50 and 20/40, respectively, which
      represents a significant improvement (P = 0.011). CONCLUSION: Precise retinal
      targeting with a navigated laser photocoagulator resulted in highly accurate
      perifoveal laser application and no foveal damage. At 6 months after the
      treatment, significant decreases in central foveal thickness and significant
      improvements in visual acuity were identified.

PMID- 21886019
TI  - Intravitreal bevacizumab for choroidal neovascularization associated with
      choroidal nevus.
AB  - PURPOSE: To report 10 cases of occult choroidal neovascularization (CNV)
      associated with choroidal nevus managed with intravitreal bevacizumab. METHODS:
      Interventional case series. Each nevus was examined and imaged with fluorescein
      angiography, B-scan ultrasonography, and optical coherence tomography. Data were
      retrospectively analyzed to evaluate outcomes of treatment response and visual
      acuity. RESULTS: Nine patients presented with CNV overlying a chronic choroidal
      nevus with a posterior margin within 1.5 mm of the foveola. In the 10th patient,
      the posterior margin of the nevus was located 10 mm from the foveola with
      extension of subretinal fluid into the macula. The CNV was subfoveolar in four
      cases, juxtafoveolar in two cases, and extrafoveolar in four cases. Initial
      visual acuity was 20/20 to 20/50 in 5, 20/60 to 20/100 in 2, and 20/200 or worse
      in 3 cases. Clinical features included subfoveolar fluid in nine, exudation in
      five, and hemorrhage in four cases. Intravitreal bevacizumab (1.25 mg/0.05 cc)
      was injected with regression of CNV in all 10 cases using 2 to 14 injections
      (median 3 injections). In 2 eyes, after therapeutic response to bevacizumab later
      consolidation with photodynamic therapy (juxtafoveolar CNV) (n = 1) or
      conventional laser (extrafoveolar CNV) (n = 1) was provided. In the remaining 8
      eyes, after discontinuation of bevacizumab, there was no recurrence of CNV over
      mean 10.1 months. At overall mean follow-up of 22.5 months, final visual acuity
      decreased by 1 line in 4 cases and improved by mean of 3 lines (range, 1-8 lines)
      in 6 cases. There were no adverse effects from bevacizumab injections. All 10
      choroidal nevi remained stable. CONCLUSION: Intravitreal bevacizumab appears to
      be an effective treatment option for CNV secondary to choroidal nevus. In some
      cases, depending on the proximity of the CNV to the foveola, photodynamic therapy
      or conventional laser may be useful adjunctive therapy.

PMID- 21886018
TI  - Topical dorzolamide for treatment of cystoid macular edema in patients with
      choroideremia.
AB  - PURPOSE: : To determine the value of a topical carbonic anhydrase inhibitor on
      the macular thickness and function in choroideremia patients with cystoid macular
      edema. METHODS: : Two choroideremia patients with cystoid macular edema, observed
      by spectral-domain optical coherence tomography, were treated with a topical form
      of carbonic anhydrase inhibitor. Examinations performed before and during
      treatment included best-corrected visual acuity by using the Early Treatment
      Diabetic Retinopathy Study charts and contrast sensitivity measured with briefly
      presented grating targets and the Pelli-Robson letter contrast sensitivity chart,
      microperimetry, and spectral-domain optical coherence tomography. RESULTS: : The
      2 choroideremia patients treated with dorzolamide 2% formulation had a noticeable
      reduction in macular thickness by spectral-domain optical coherence tomography.
      This reduction was found in both eyes after 2 months of treatment. After an
      additional 3 months of the same treatment regimen, a more noticeable reduction in
      macular thickness was observed. The two study patients had improvement of their
      visual acuity, in at least one eye, on Early Treatment Diabetic Retinopathy Study
      charts, but no clinically significant changes for the other measures of visual
      function. CONCLUSION: : The present study shows the potential efficacy of topical
      dorzolamide for treating choroideremia patients with cystoid macular edema.

PMID- 21886020
TI  - Diagnostic and therapeutic challenges.

PMID- 21886021
TI  - Vitrectomy outcomes in eyes with high myopic macular hole without retinal
      detachment.
AB  - PURPOSE: The purpose of this study is to evaluate the vitrectomy outcomes for
      high myopic patients with macular hole (MH) without retinal detachment and to
      compare these outcomes with those of control patients with idiopathic MH
      undergoing similar surgeries by the same surgeon. METHODS: The study was designed
      as a matched, case-control, retrospective chart review. We performed a
      retrospective chart review of consecutive cases that underwent vitrectomy for MH
      without retinal detachment from 2000 through 2008. Twenty-four eyes of 24
      patients were selected to participate in this study. They were divided into 2
      groups: 12 study eyes with high myopic MH without retinal detachment and 12
      control eyes with idiopathic MH. The main outcomes were preoperative,
      postoperative best-corrected visual acuity (BCVA), MH closure rates, and
      complications in both groups. RESULTS: There was a closure rate of 100% in both
      the study and control groups, and no cases of reopening were reported during the
      follow-up visits. After surgery, the mean BCVA of the study group remained
      stable. There was no significant improvement of mean BCVA after surgery (P =
      0.35) in the study group. The mean BCVA of the control group improved
      significantly (P = 0.00) after surgery. The mean postoperative BCVA in the study
      group was significantly lower than that in the control group in a comparison
      using the Student's t-test (P = 0.01). In the study group, the BCVA improved or
      remained stable after surgery in 8 eyes (67%). In the control group, the BCVA of
      all eyes improved or remained stable. The proportion of eyes with BCVA
      improvement after surgery was significantly higher in the study group than in the
      control group (P = 0.03). Disappearance of the outer nuclear layer and
      photoreceptor layer in the foveola and thinning of the foveola was showed in the
      postoperative optical coherence tomography images of four eyes in the study group
      while in none of the eyes in the control group. CONCLUSION: In summary,
      vitrectomy results in satisfactory anatomical improvement in patients with high
      myopic MH without retinal detachment. However, the visual acuity outcomes of the
      high myopic MH patients without retinal detachment were poorer than those for
      patients with idiopathic MHs.

PMID- 21886022
TI  - Axial length increases and related changes in highly myopic normal eyes with
      myopic complications in fellow eyes.
AB  - PURPOSE: To determine whether the axial length (AL) in highly myopic normal adult
      eyes with myopic complications in the fellow eyes increases significantly during
      a 1-year interval and to investigate the relationships between the changes in the
      AL and different ocular parameters. METHODS: The medical records of 20 highly
      myopic normal eyes whose fellow eyes had myopic complications were reviewed. The
      AL, subfoveal choroidal thickness, height of a posterior staphyloma, and length
      of the retinal pigment epithelium from the fovea to 3-mm superior, inferior,
      nasal, and temporal retina were measured twice at an interval of approximately 1
      year. The changes in these ocular parameters and their correlations were
      investigated. RESULTS: The AL increased, the choroid became thinner (both P <
      0.001), the superior (P < 0.05) and temporal (P < 0.01) staphyloma height
      increased, and the superior and temporal retinal pigment epithelial length
      increased (both P < 0.01). All the changes were significant. Stepwise analyses
      indicated that the factor most associated with the increase in the AL was the
      increase in the superior retinal pigment epithelial length (P < 0.001).
      CONCLUSION: Our results indicate that the AL can increase significantly in highly
      myopic normal adult eyes during a 1-year interval, and the increase in the
      posterior staphyloma height is the most likely cause for the increased AL.

PMID- 21886023
TI  - Prevalence and risk factors for diabetic retinopathy: the Beijing Communities
      Diabetes Study 6.
AB  - BACKGROUND: To examine prevalence and associated factors of diabetic retinopathy
      in patients with Type 2 diabetes mellitus in urban communities of Beijing.
      METHODS: The community health care center-based study included subjects with
      diabetes mellitus and an age of 20 years to 80 years, who were recruited from 15
      community health centers in urban Beijing. Diabetes mellitus was defined using
      the World Health Organization criteria. Fundus photographs were graded using the
      modified Airlie House classification system. RESULTS: Of 2,642 eligible patients,
      2,007 (76.0%) subjects (1,199 women) with a mean age of 64.1 +/- 9.0 years
      participated. The overall prevalence of diabetic retinopathy was 24.7 +/- 1.0%
      (95% confidence interval [CI], 22.8-26.6). In binary logistic analysis, presence
      of diabetic retinopathy was associated with younger age (odds ratio [OR], 0.97;
      95% CI, 0.95-0.98), longer duration of diabetes (OR, 1.10; 95% CI, 1.08-1.12),
      higher concentration of glycosylated hemoglobin HbA1c (OR, 1.23; 95% CI, 1.14
      1.33), higher systolic blood pressure (OR, 1.01; 95% CI, 1.01-1.02), lower body
      mass index (OR, 0.95; 95% CI, 0.92-0.98), and elevated blood urea concentration
      (OR, 1.01; 95% CI, 1.00-1.01). Microalbuminuria was an additional associated
      factor (OR, 1.55; 95% CI, 1.16-2.08). Patients with microalbuminuria were 4.7
      times more likely to have a severe or proliferating diabetic retinopathy than
      those without microalbuminuria. CONCLUSION: In the urban population of Beijing,
      prevalence of diabetic retinopathy in diabetic patients was 25%. As in whites,
      increased blood pressure besides elevated plasma glucose concentrations was
      highly significantly associated with diabetic retinopathy in Chinese. It suggests
      that in Chinese as also in whites, blood pressure control beside control of
      plasma glucose levels is important to prevent development or progression of
      diabetic retinopathy.

PMID- 21886024
TI  - Incorporating new therapy into established clinical practice guidelines.

PMID- 21886025
TI  - Assessment of atrial electromechanical coupling characteristics and P-wave
      dispersion in patients with atrial septal aneurysm.
AB  - OBJECTIVE: The aim of this study was to evaluate atrial conduction abnormalities
      obtained by Doppler tissue imaging (DTI) and electrocardiogram analysis in Atrial
      septal aneurysm (ASA) patients. METHODS: A total of 30 patients with ASA (11
      males/19 females, mean age 29.6 +/- 11.3 years) and 25 controls (9 males/16
      females, mean age 27.6 +/- 9.98 years) were included. Interatrial and intraatrial
      electromechanical coupling (PA) intervals were measured with DTI. P-wave
      dispersion (Pd) was calculated from the 12-lead electrocardiogram. Systolic and
      diastolic left ventricular (LV) functions were measured by using conventional
      echocardiography and DTI. RESULTS: Atrial electromechanical coupling at the left
      lateral mitral annulus (PA lateral) was significantly delayed in ASA patients
      (59.3 +/- 4.2 vs. 48.5 +/- 1.1 ms, P < 0.0001). Interatrial (PA lateral--PA
      tricuspid) and intraatrial (PA septum--PA tricuspid) electromechanical coupling
      interval were significantly longer in ASA patients (26.1 +/- 6.2 vs. 14.4 +/-
      6.75 ms, P < 0.0001 and 9.04 +/- 1.1 vs. 5.4 +/- 2.5 ms, P < 0.0001). maximum P
      wave (Pmax) duration and Pd were significantly longer in ASA patients (98.3 +/-
      8.1 vs. 86.4 +/- 7.8 ms, P < 0.001 and 20.7 +/- 0.9 vs. 12.3 +/- 1.5, P <
      0.0001). Systolic and diastolic left ventricular functions of both groups were
      comparable. CONCLUSION: This study shows that atrial electromechanical coupling
      intervals and Pd are delayed in ASA patients.

PMID- 21886026
TI  - Geographic variations in percutaneous coronary interventions and coronary artery
      bypass graft surgery among Tennessee elders.
AB  - OBJECTIVES: Coronary heart disease often presents with ST segment elevation acute
      myocardial infarction (STEMI). The American College of Cardiology/American Heart
      Association guidelines stress prompt reperfusion for STEMI. Examining geographic
      variations in treatment with PPCI (percutaneous primary coronary intervention)
      and CABG (coronary artery bypass graft) among metropolitan, micropolitan and non
      micropolitan rural residents provides a descriptive basis for generating
      hypotheses concerning place and receipt of guidelines-based treatment. METHODS:
      Using ICD-9 codes for STEMI and excluding beneficiaries with pre-existing MI in
      claims data, yielded a subset of 18,775 Tennessee Medicare beneficiaries
      experiencing STEMI from 1996 to 2002. The outcome variable is type of treatment,
      i.e., in accord (PPCI or CABG present) or not in accord (PPCI or CABG absent)
      with guidelines. Independent variables include type county residence, hospital
      volume, race, gender, and age. Analyses include cross-tabulation and logistic
      regression, estimating separate models by age and type of MI. RESULTS:
      Micropolitan residents with STEMI have the lowest rates for PPCI (18.8%) versus
      28.1% percent for metropolitan and 24.2% for non-micropolitan rural residents.
      CABG follows similar patterns at lower overall rates. Treatment at a heart center
      with high volume PPCI mediated the relationship between the likelihood of PPCI
      and place. CONCLUSION: The correspondence between metropolitan and rural
      utilization suggests that access to a full range of treatment options and
      likelihood of "best practice" care is not dependent on metropolitan residence.
      This presents the possibility that with some policy changes, e.g., centralization
      of emergency heart care, the same may ultimately be true for micropolitan
      residents.

PMID- 21886027
TI  - Willingness for weight loss intervention among overweight and obese inpatients.
AB  - OBJECTIVES: To determine whether overweight and obese inpatients are receptive to
      weight-loss interventions while hospitalized and whether interest in weight-loss
      intervention correlates with accurate self-perception of weight. METHODS: We
      conducted a cross-sectional survey of overweight and obese patients admitted to
      the general medicine service at a large urban academic medical center from
      September 17, 2007 through October 16, 2007. Subjects were identified based on
      body mass index (BMI) on admission >=25 and surveyed using a 14-question
      instrument. The main outcome measure was patient willingness to consider weight
      loss intervention. RESULTS: Of 67 eligible patients, 64 (95.5%) agreed to be
      interviewed. BMI ranged from 25 to 50. Overall, 52.6% (10 of 19) of overweight
      patients did not believe they were overweight and 46.7% (21 of 45) of those with
      a BMI over 30 were unaware that they met criteria for obesity. Among all patients
      surveyed, 56.3% stated they would be interested in weight-loss intervention while
      hospitalized. In obese patients specifically, 68.9% expressed interest. Interest
      correlated with BMI (Pearson correlation coefficient (r) = 0.261, P = 0.04),
      accurate self-perception of weight (P = 0.03), diagnostic delays related to
      weight (P = 0.01) and a history of past weight-loss attempts (P = 0.04). None of
      the patients we interviewed received weight-loss intervention of any kind while
      hospitalized. CONCLUSION: Inpatients who recognize that they are overweight or
      obese are interested in pursuing weight-loss initiatives. Despite their interest,
      most do not receive weight-loss interventions while hospitalized.

PMID- 21886028
TI  - Effect of clinical vignettes on senior medical students' opinions of climate
      change.
AB  - OBJECTIVES: The consequences of climate change directly threaten human health.
      Some have argued that, as such, doctors have a special duty to solve climate
      change. Despite such recommendations, to our knowledge, there has been no
      previous work documenting physician attitudes on climate change, or the stability
      of those opinions. METHODS: We invited 523 fourth-year medical students to a
      survey asking their opinion on climate change and their opinion regarding one of
      two fictional medical vignettes. In the vignettes, which are analogous to the
      climate change issue, students decide whether to discontinue a drug that may be
      adversely affecting laboratory values. In the climate change question, students
      are asked whether the United States should take efforts to discontinue the use of
      fossil fuels. Students are randomized to the order in which they receive the
      questions. RESULTS: Ninety-five percent (95% CI 89.1%-100%) of students initially
      asked about climate change feel the United States should take steps to curb
      carbon dioxide emissions, while only 73% (95% CI 57.5%-89.2%) of students respond
      similarly if first given an analogous patient vignette. Conversely, in all cases
      where a fictional medical vignette follows the climate change question, students
      are more likely to cease using a potentially harmful agent (66% CI 53.5%-71.8%
      vs. 52% CI 43.3%-67.1%). CONCLUSION: Our results suggest that student physician
      attitudes to climate change are mutable. Priming students into "medical mode" may
      alter their opinions on the scientific merit of nonmedical issues, and may be a
      vestige of a hidden medical curriculum. Further studies should explore the
      interrelationship between other sociopolitical beliefs and medical decision
      making.

PMID- 21886029
TI  - Venous lower-limb evaluation in patients with acute pulmonary embolism.
AB  - OBJECTIVES: Compressive ultrasonography (CUS) of the lower limbs is the first
      choice for identifying deep venous thrombosis (DVT) in patients with symptomatic
      pulmonary embolism (PE). The aim of this study was to uncover clinical
      characteristics and CUS findings in patients with proven PE and their
      correlations with PE extent. METHODS: A total of 524 consecutive cases of proven
      symptomatic PE diagnosed between January 1996 and December 2006 were reviewed.
      RESULTS: Mean age was 71.06 +/- 14.43 SD years; 244 patients (46.6%) were men.
      DVT signs or symptoms were present in 30.9% of patients and were associated with
      the femoral site (P = 0.029). CUS was performed in 383 patients (73.1%) and DVT
      was found in 75.5%. In 94.1% of patients DVT was proximal (popliteal and/or
      femoral), which would have been then identified by simplified CUS. CUS was
      performed significantly more often in presence of signs or symptoms of DVT (P <
      0.001), less often in presence of medical illnesses (P = 0.040), age >=75 years
      (P = 0.001) and death in hospital (P < 0.001). Signs or symptoms of DVT were
      predictors of positive CUS (P < 0.001), presence of medical illnesses (P =
      0.020), central venous catheter (P = 0.035), death in hospital (P = 0.032) were
      predictors of negative CUS findings. Neither clinical findings nor CUS were
      associated with PE extent. CONCLUSIONS: In patients with proven symptomatic PE,
      signs or symptoms of DVT are present only in 1/3 of cases and are significantly
      more frequent when DVT is extended to the femoral vein. Simplified CUS of the
      lower limbs has a high sensitivity in finding proximal DVT. CUS is not able to
      predict PE extent.

PMID- 21886030
TI  - National survey of physicians' perception of the cause, complications, and
      management of gastroparesis.
AB  - OBJECTIVES: Manifestations of gastroparesis are heterogeneous and clinical
      complications are poorly defined. Misconceptions of gastroparesis may be common.
      The objective was to determine physicians' perception of gastroparesis and
      identify areas that need further research and education. METHODS: A physician
      survey was prospectively developed and tested. The survey included questions on
      the etiology, symptoms, management and perceived complications of gastroparesis.
      Physicians' feedback included rated responses by Likert scale and ranked
      responses by priority. A total of 3658 surveys were mailed to gastroenterologists
      and general practitioners using an online physician directory and a local medical
      society directory. Analysis of variance and t test were utilized. RESULTS: A
      total of 397 surveys were returned. 85.9% of responses were from the national
      survey and 14.1% were local. Physicians ranked diabetes (70%) as the most common
      cause of gastroparesis, followed by idiopathic (21%) and postsurgical (9%).
      Postprandial epigastric pain (61%) was ranked as the most frequent symptom of
      gastroparesis, followed by retching/vomiting (20%) and heartburn/regurgitation
      (19%). 60% believed scintigraphy t1/2 is an accurate measurement of gastric
      emptying. Only one-third believed gastric electrical stimulation was effective as
      treatment of gastroparesis. Physicians rated abdominal pain as the most
      clinically significant complication of gastroparesis surpassing weight loss,
      hospitalization for dehydration, and malnutrition (P < 0.01). There were small
      but statistically significant differences between gastroenterologists versus
      general practitioners and private versus academic physicians. CONCLUSION: More
      physician awareness and education is needed on gastroparesis and the standardized
      four-hour gastric scintigraphy method, as well to clarify the management strategy
      for this condition.

PMID- 21886031
TI  - Characteristics of CPOE systems and obstacles to implementation that physicians
      believe will affect adoption.
AB  - BACKGROUND: Computerized Physician Order Entry (CPOE) has the potential to
      decrease medical errors and improve quality. Our health system plans to implement
      CPOE in response to the ARRA HITECH Act. OBJECTIVES: To determine (A) physicians'
      projections of the most important characteristics of a CPOE system that will
      affect their willingness to adopt CPOE, and (B) the obstacles they foresee in
      adopting CPOE. METHODS: All members of our health system's physician quality
      organization were invited to participate in a confidential survey. RESULTS: Two
      hundred twenty-four of 549 (41%) recipients responded to the survey. Respondents
      ranked "disruption in my work routine" (72%) and "improve efficiency in placing
      orders" (63%) as the two most important characteristics that would affect their
      utilization of CPOE. They believed CPOE would enable orders to be placed more
      efficiently (3.3, sd = 1.2), carried out rapidly (3.4, sd = 0.9), and have fewer
      errors (3.7, sd = 0.9). The most commonly cited obstacles to CPOE implementation
      were: Efficiency-Inefficiency (23%), Hardware Availability (12.7%), Computer
      Restrictions (10.8%), Training (8.8%), Simplicity - Ease of Use (8.5%), and
      Physician Buy-in (8.1%). CONCLUSIONS: The majority of physicians believed CPOE
      would lead to a reduction of medical errors and more efficient patient care.
      However, physicians are highly concerned with how CPOE will affect their own work
      efficiency.

PMID- 21886032
TI  - Lack of association between chemokine receptor 5 (CCR5) delta32 mutation and
      pathogenesis of asthma in Iranian patients.
AB  - BACKGROUND: Chemokines and their receptors are clinically important mediators, as
      the chemokine receptors are expressed on almost all immune cells. They play
      pivotal roles in pathogenesis of almost all clinical situations including asthma.
      Correspondingly, MIP-1alpha (CCL3), MIP-1beta (CCL4), and RANTES (CCL5) are among
      the important chemokines involved in the pathogenesis of asthma. These chemokines
      bind to the CCR5 (their related receptor) on the cell surfaces. Attachment of
      related chemokine ligands to CCR5 plays an important role in the pathogenesis of
      asthma; hence, this study aimed to analyze delta32 mutations in CCR5 in asthmatic
      patients. MATERIAL AND METHODS: This experimental study was undertaken on 162
      asthmatic patients and 200 healthy controls during February to June 2008 at
      Rafsanjan University of Medical Sciences. The Gap-PCR method was applied to
      analyze the delta32 mutation in the CCR5 gene, and demographic data (eg, age,
      sex, occupation, socio-economic status) were collected using a questionnaire.
      RESULTS: The findings of this study indicated that none of the asthmatic patients
      exhibited delta32 mutation in CCR5 chemokine receptor while only 3 (1.5%) of
      controls had the heterozygotic form of this mutation. DISCUSSION: Several
      research groups analyzed delta32 mutations in CCR5 in different diseases,
      including asthma. Some investigations reported a significant relation between
      asthma and delta32 mutations in CCR5, but there are also many reports which
      failed to find a relation between asthma and this mutation. Based on the results
      of this study and others, it seems that the delta32 mutation does not affect the
      pathogenesis of asthma.

PMID- 21886033
TI  - Place in therapy for liraglutide and saxagliptin for type 2 diabetes.
AB  - BACKGROUND: The release of incretin based therapeutic entities has brought the
      possibility to offer control of the disease by augmenting a natural process in
      the body that has become deficient with type 2 diabetes. Liraglutide, an incretin
      mimetic, and saxagliptin, a dipeptidyl peptidase-4 inhibitor, have been approved
      and introduced to the market. OBJECTIVES: To (a) review the efficacy and safety
      data of for the treatment of type 2 diabetes, and (b) recommend their place in
      therapy. METHODS: A MEDLINE search was performed using key words "liraglutide"
      and "saxagliptin" for articles published and available through July 2010.
      RESULTS: The Liraglutide Effect and Action in Diabetes (LEAD) trials encompassed
      six published phase 3 trials that evaluated the efficacy and safety of
      liraglutide either as monotherapy or in addition to oral hypoglycemic
      medications. Saxagliptin has been studied as monotherapy and in combination to
      oral hypoglycemic medications. CONCLUSIONS: Liraglutide has been shown to improve
      glucose control and weight loss compared to other pharmacologic treatments with
      diabetes and may offer improved control with a decrease in daily dosing compared
      to exenatide. Saxagliptin improved glucose control as monotherapy or in
      combination with medications other than sulfonylurea. Saxagliptin has not been
      evaluated head to head with sitagliptin other than in combination with metformin
      where saxagliptin was deemed noninferior. Given the lack of long-term safety and
      clinical data compared to current treatment modalities, and more importantly the
      overall cost of the therapies to the health care system, a global recommendation
      for their use cannot be issued.

PMID- 21886034
TI  - Multimodality FDG PET/CT appearance of pulmonary tuberculoma mimicking lung
      cancer and pathologic correlation in a tuberculosis-endemic country.
AB  - OBJECTIVES: Differentiation between pulmonary tuberculoma and malignancy by
      preoperative diagnostic imaging sometimes proves difficult. The purpose of this
      study is to investigate variable manifestations of pulmonary tuberculoma
      mimicking lung cancer on fluorodeoxyglucose (FDG) positron emission
      tomography/computed tomography (PET/CT) image and pathologic correlation.
      PATIENTS AND METHODS: Twenty-five patients with a high suspicion of malignancy
      and histopathologically diagnosed as pulmonary tuberculoma were included. Their
      FDG PET/CT images, clinical data, and pathologic findings were investigated.
      RESULTS: There were 18 men and seven women. The mean age was 52 +/- 8.8 years.
      The maximal diameter of pulmonary tuberculoma ranged from 1.7 to 4.2 cm. CT scan
      revealed that abnormal signs associated with malignancy such as spicular
      radiation, notching, and pleural indentation also frequently manifested in
      tuberculoma. During early imaging, positive FDG uptake was identified in 21
      patients (84%), intermediate uptake in 3 patients (12%) and negative uptake in 1
      patient (4%). During delayed imaging, 16 patients (64%) showed persistent
      elevated FDG accumulation and 8 patients (32%) experienced a slight drop of FDG
      accumulation. Pathologically active tuberculoma showed significantly higher FDG
      radioactivity during both early and delayed imaging than inactive lesion (P <
      0.05). Lymphadenopathy with positive FDG uptake was identified in nine patients
      (36%). CONCLUSION: Pulmonary tuberculomas mimicking lung cancer, most of which
      were pathologically active lesions, commonly displayed abnormal appearances in CT
      scan and an increase in FDG uptake, similar to changes seen on malignancy.
      Coexistent lymphadenopathy made differential diagnosis even more complicated.
      These results suggested that positive FDG PET/CT findings should be interpreted
      with caution in tuberculosis-endemic regions.

PMID- 21886035
TI  - Brief intervention for perpetration of intimate partner violence (IPV):
      simulation versus instruction alone.
AB  - OBJECTIVE: To compare two brief randomized computer-based interventions about
      perpetration of intimate partner violence (IPV). METHODS: The study was a
      prospective cross-sectional cohort study of patients during randomized 4-hour
      shifts in an urban hospital-based emergency department setting with an emergency
      medicine residency. The site is a level 1 trauma center emergency department with
      an annual census of 60,000 adults. A touch-screen computer program was developed
      in Visual Basic 2005 Studio with consecutive data entry screens. A series of
      questions to evaluative IPV knowledge, attitude, and practices (KAP) was given
      before and after the brief intervention. The subjects were randomized to one of
      two intervention groups. Both groups were shown a set of PowerPoint slides
      addressing IPV prevention, which was followed by either a control group with
      nothing further (control) or a five-minute simulation video depicting IPV
      perpetration in adults (SIM). The main outcome was the net improvement in KAP
      scores defined as number who improved minus number who did worse. Perpetrators
      and victims were assessed separately. Demographics were also obtained. For
      demographics, descriptive statistics and percentages were used. Wilcoxon signed
      rank test was used for pre-post test paired data. RESULTS: A total of 239
      patients, presenting during 52 randomized four-hour shifts, completed the study;
      118 were in the control group, 121 in SIM; 115 (48%) were male and 124 (51 %)
      female (9 unknown). Most participants were from 21 to 30 years old (38%); 77
      (32%) were Hispanic and 100 (42%) were white. There was an overall improvement in
      responses to KAP questions with correct answers to all questions in 46% before vs
      59% after the computer intervention (Diff 13% 95% confidence interval [CI] 4-22).
      The net improvement in KAP score in the control group was 8% and in the SIM group
      it was 22% (Diff = 15%, 95% CI = 6-24). Forty subjects (17%, 95% CI = 12-21) were
      perpetrators and 52 subjects (22%, 95% CI = 17-27) were victims. KAP scores were
      not significantly improved in the SIM group over the control for either
      perpetrators or victims. CONCLUSION: An IPV simulation video resulted in a
      greater percent of subjects showing improvement in knowledge, attitudes, and
      practices about IPV perpetration. A brief IPV simulation video intervention can
      be performed in a busy emergency department setting.

PMID- 21886036
TI  - Recent diabetes issues affecting the primary care clinician.
AB  - Diabetes accounts for millions of office visits each year to primary care offices
      in the United States. Successful care of the patient with type 2 diabetes
      requires not only focus on glucose management but also on comorbidities such as
      hypertension, dyslipidemia and obesity which are closely linked to microvascular
      and macrovascular complications. Primary care clinicians must stay abreast of
      frequently published diabetes literature and new treatments to care for these
      increasingly complex patients. Metformin and its effect on B12 absorption
      continues to be an issue encountered by clinicians in daily clinical practice.
      There has also been recent discussion regarding the increased risk of diabetes
      with statins; data to date on this issue have been conflicting. Rosiglitazone
      continues to face public scrutiny and there are now Food and Drug Administration
      regulations regarding its increased risk of cardiovascular disease. Liraglutide
      and saxagliptin represent new treatment options for type 2 diabetes, increasing
      the available options for treating this complex disease. A review of the primary
      literature involving these topics is provided.

PMID- 21886037
TI  - Nephrolithiasis: history counts.

PMID- 21886038
TI  - Fibromyalgia, fact or fiction: let's put our feelings aside.

PMID- 21886039
TI  - Atomoxetine and myocardial infarction.

PMID- 21886044
TI  - Association of Helicobacter pylori infection with the development of colorectal
      polyps and colorectal carcinoma.
AB  - BACKGROUND AND AIMS: Recent studies have suggested a possible association between
      Helicobacter pylori (HP) infection and colon neoplasia. HP infection causes
      hypergastrinemia, and gastrin increases colorectal mucosal proliferation,
      potentially leading to colorectal cancer. We investigated whether HP infection is
      associated with colon neoplasia. METHODS: We conducted a cross-sectional, single
      center study in which patients who underwent routine outpatient colonoscopy and
      were tested for HP infection on esophagogastroduodenoscopy from January 1, 2008
      to November 1, 2009 were identified. Patient demographic data (gender and age)
      and information on colon polyp characteristics (size, number of polyps, location,
      morphology, and histology) were abstracted from retrospective chart review.
      Presence of adenoma/carcinoma was compared in the HP-positive cases and HP
      negative controls. RESULTS: A total of 192 patients were included in the study,
      with 96 patients each in the HP-positive and -negative groups. The two groups did
      not differ significantly in gender, age, polyp size, number of polyps, polyp
      location, morphology, and histology. Adenomatous colon polyps were noted in 31%
      of the HP-positive cases and in 26% of the HP-negative controls (P = 0.52). Colon
      carcinoma was found in 6% of HP-positive and 2% of HP-negative patients (P =
      0.28). CONCLUSION: The higher prevalence of adenomatous colon polyps/carcinoma in
      HP-positive patients compared to HP-negative patients was not statistically
      significant. Larger studies are needed to examine further the potential
      association between HP infection and colorectal adenoma/carcinoma.

PMID- 21886043
TI  - Role of sociocultural factors in hepatitis B screening among Asian Americans.
AB  - OBJECTIVE: To apply the proposed Sociocultural Health Behavior Model to determine
      association of factors related to hepatitis B virus (HBV) screening among Asian
      Americans. METHODS: A cross-sectional design of 1312 Asian men and women 18 years
      and older. The frequency distribution analysis and chi square analysis were used
      for the initial screening of the following variables: access/satisfaction with
      health care, enabling, predisposing, cultural, and health belief factors.
      Univariate and multivariate analyses were conducted on factors for HBV screening
      using logistic regression analysis. RESULTS: Correlates to HBV screening included
      demographics, cultural factors, enabling factors, and family/social support
      factors. Enabling factors were more likely to be associated with HBV screening.
      CONCLUSION: The model highlights the role sociocultural factors play in HBV
      screening. Findings reinforce the need for HBV screening programs and indicate
      programs could be more effective if they included these components and were
      sensitive to ethnic and cultural factors.

PMID- 21886045
TI  - Nondermatologists' use of predictive terms for a potentially malignant lesion.
AB  - BACKGROUND: Skin cancer is frequently suspected by nondermatologists. Many
      dermatology practices currently do not triage referrals from nondermatologists.
      Little is known how nondermatologists describe lesions of concern when making
      referrals. OBJECTIVE: We sought to assess the descriptive terminology used by
      nondermatologists when referring patients with potential cutaneous malignancies.
      METHODS: We completed a retrospective chart review of 400 patients referred by
      nondermatologists for skin lesions suspicious of malignancy. We collected the
      reason for the consult, all terminology used to characterize the lesion, and the
      final diagnosis. RESULTS: Clinicians documented 680 reasons for referring
      patients with suspicious lesions. General concern (rule out malignancy) without
      specific descriptors was used in 78 referrals, of which 23% (n = 18) were found
      to be associated with malignancy. Specific descriptive terminologies used most
      frequently by nondermatologists to describe suspicious lesions were:
      hyperpigmented (n = 71), changing size (n = 69), nonhealing (n = 55), irregular
      border (n = 52), irritated and/or scaly (n = 40), and raised (n = 33). A
      statistically significant correlation (P < 0.05) was found between skin cancer
      and the following terms: nonhealing, ulcerated, and rule out basal cell
      carcinoma. CONCLUSION: The descriptive terminology of potential cutaneous
      malignancies utilized by nondermatologists may provide important clues to aid
      dermatologists in triage decisions. Specifically, ulcerated, nonhealing, and rule
      out basal cell carcinoma may be terms that indicate the patient should be seen by
      the dermatologist in a timely manner.

PMID- 21886046
TI  - Trends in hip fracture-related mortality in Texas, 1990-2007.
AB  - BACKGROUND: There are limited data about trends in hip fracture-related
      mortality. In this study, we examined temporal trends in hip fracture mortality
      rates among persons aged 50 years or older in Texas between 1990 and 2007.
      MATERIALS AND METHODS: Hip fracture-related mortality was defined as a death on
      the multiple cause of death record for which hip fracture was listed as a
      contributing cause. Population estimates for Texas were used as the denominator
      to calculate mortality rates per 100,000 persons. The joinpoint regression
      analysis was used to identify points where a statistically significant change
      occurred in the linear slope of the rates. RESULTS: A total of 14,350 death
      certificates listed hip fracture as a contributing cause of death. Hip fracture
      rates decreased predominantly among men by 0.8% (95% CI, -1.5 to -0.1) per year.
      Conversely, age-adjusted rates among women increased by 0.3% (95% CI, -0.4 to
      1.0) per year. By race/ethnicity, hip fracture mortality rates increased annually
      2.2% (95% CI, -0.1 to 4.4) among blacks, whereas the rates among whites and
      Hispanics remained steady. Moreover, the proportion of death records that listed
      nursing homes and residence as a place of death increased by 2.2% (95% CI, 1.6 to
      2.9) and 8.7% (95% CI, 6.3 to 11.0) per year, respectively. CONCLUSION: Hip
      fracture mortality rates decreased predominantly among men in Texas during the
      study period. Increasing hip fracture mortality rates among blacks and nursing
      home residents merit further research.

PMID- 21886047
TI  - Update on trends for inpatient surgical management of tubal ectopic pregnancy in
      Maryland.
AB  - OBJECTIVES: In Maryland, an analysis from 1994-1999 found that most hospitalized
      patients with tubal pregnancy underwent extirpative operations. The objective of
      this study was to determine whether practice patterns had changed over time.
      METHODS: Using the Maryland Health Service Cost Review Commission (HSCRC)
      database from January 1, 2000-December 31, 2004, subjects were identified by ICD
      9 code 633.1, tubal pregnancy. The incidence of hospitalization was estimated
      based on state census data. Cases were analyzed by demographics, presentation,
      surgeon volume for ectopics, surgical treatment, length of stay, and charges.
      RESULTS: There were 2292 cases of tubal pregnancy identified, yielding an
      incidence for hospitalization of 4.81 per 10,000 women. The mean age of subjects
      was 29.6. Most were admitted through the emergency department (76.8%).
      Extirpative procedures were used in 88.01%. ER admission and increasing age were
      associated with extirpative surgery. Mean length of stay was 1.86 days; mean
      total charges were $5480.11. CONCLUSIONS: A greater percentage of hospitalized
      ectopics were treated radically than prior. This may be due to acuity of
      presentation or regional surgical practices and preferences. Continued
      surveillance and a move toward improvement of Maryland's outcomes for ectopic
      pregnancy is needed. We propose an algorithm for emergency triage and management
      of pregnancy in an unknown location toward this end.

PMID- 21886048
TI  - Gender differences with respect to psychiatric comorbidity in obstructive sleep
      apnea syndrome.
AB  - OBJECTIVES: Psychiatric disorders are common in obstructive sleep apnea syndrome
      (OSAS); however, interrelating factors influencing psychiatric comorbidity (PC)
      in OSAS are unclear. The aim of this study is to investigate gender related
      differences with PC in OSAS. METHODS: Data of patients diagnosed as OSAS in
      University of Gaziantep from January 2006 to January 2010 were retrospectively
      evaluated. Polysomnographic data were recorded with Viasys Sleep Screen (Viasys
      Healthcare, Germany). Patients younger than 18 years old were excluded. RESULTS:
      PC was present in 53.1% of OSAS patients. The rate of male subjects with PC was
      42.6%; however, 76.26% of females had PC (P = 0.00). Age (P = 0.00) and body mass
      index (BMI) (P = 0.00) were higher in patients with PC. Ferritin levels were
      lower in patients with PC (P = 0.00). Male subjects with PC were older and had
      lower sleep efficiency and longer rapid eye movement latency than males without
      PC. BMI was the only contributory factor to PC in female subjects. CONCLUSION: PC
      in OSAS is common, especially in females. Apnea hypopnea index does not seem to
      influence probability of PC.

PMID- 21886049
TI  - Chronic idiopathic neutrophilia: experience and recommendations.
AB  - OBJECTIVES: To distinguish chronic idiopathic neutrophilia (CIN) in a cost
      effective manner from neutrophilia caused by important underlying illnesses.
      METHODS: This was a retrospective review of patients visiting a Veterans Affairs
      Medical Center over the last 10 years with a diagnosis of leukocytosis or
      myeloproliferative disorder. Of this group, fifty-seven patients from 1999 to
      2008 were identified with CIN. Clinical and laboratory parameters were examined
      to identify CIN and establish its course. Eighty-one patients who presented from
      2005 to 2010 with myeloproliferative disorders were also studied at time of
      diagnosis to determine any possible confusion with CIN. RESULTS: The patients
      with CIN were followed for a mean of >= 7.3 years without progression to other
      serious disorders. Compared to non-CIN patients evaluated for neutrophilia, in
      multiple logistic regression analyses, smoking (P = .001) and increased BMI (P =
      .004) were significantly associated with CIN. No CIN patient developed a
      clinically apparent myeloproliferative disorder other than chronic myeloid
      leukemia (CML). Of the patients with myeloproliferative neoplasms reviewed at the
      time of their initial diagnosis, only CML occasionally presented with a picture
      consistent with CIN. For nonsmokers, the BMI of CIN patients was significantly
      higher than the average VA population (P < .001). CONCLUSION: Cigarette smoking
      and obesity are confirmed as factors associated with CIN and may be causative.
      CIN is unlikely to develop into a clinically recognizable myeloproliferative
      neoplasm other than CML. Cost-effective guidelines for the diagnostic evaluation
      of neutrophilia in otherwise healthy patients are presented.

PMID- 21886050
TI  - Prevalence and self-reported medical history of overweight in a cardiac stress
      testing population.
AB  - OBJECTIVES: To determine the prevalence of overweight in a cardiac stress testing
      population, and the percentage of subjects who indicate a history of overweight.
      METHODS: A total of 251 consecutive subjects presenting for cardiac stress
      testing in a 450-bed community hospital from June to September 2010 were asked to
      complete a survey booklet. The survey included all patients presenting for stress
      testing, regardless of indication. Participants were subjects, ages 18 or older,
      and male or female. Exclusion criteria were medical (eg, pain), psychiatric (eg,
      psychosis), or intellectual disturbances that would preclude the successful
      completion of a survey booklet. RESULTS: Of the 251 participants 76.5% were
      overweight (BMI >= 25). Among the overweight participants, only 16.1% indicated a
      history of overweight. CONCLUSIONS: A high prevalence of overweight/obese
      individuals exists in a cardiac stress test population. A majority of overweight
      and obese patients did not indicate a history of overweight. These results
      indicate poor patient recognition and/or ineffective physician-to-patient
      education concerning unhealthy body weight. Greater and more effective efforts
      are needed to effectively educate patients about this modifiable risk factor for
      a myriad of health problems.

PMID- 21886051
TI  - Staphylococcus lugdunensis: an emerging pathogen.
AB  - OBJECTIVE: To evaluate the clinical relevance and impact of an emerging bacterial
      pathogen, Staphylococcus lugdunensis, in a large teaching hospital. METHODS:
      Three-year retrospective microbiological and clinical review of all S.
      lugdunensis isolates from a single medical center. RESULTS: Seventy-seven
      isolates were identified; 70 had complete data. Soft tissue, bone, joint, central
      nervous system, urine and bloodstream infections occurred. Soft tissue infections
      were primarily abscesses. There were four infections of prosthetic joints and
      nine cases of osteomyelitis. There were 21 bacteremias, 5 of which were
      associated with endocarditis; 2 died. Most isolates were penicillin resistant.
      CONCLUSION: S. lugdunensis has emerged as a major human pathogen, capable of
      causing significant infections at many sites. It should never be dismissed as a
      contaminant without careful review.

PMID- 21886052
TI  - Splenic injury from colonoscopy: a review and management guidelines.
AB  - Splenic injury is an uncommon complication of colonoscopy. Less than 100 cases
      are reported in the English language literature. The exact mechanism of injury to
      the spleen during colonoscopy is unknown; various authors propose several risk
      factors and possible mechanisms. Splenic injury can be graded or classified
      according to the extent of laceration and the severity of the resultant hematoma.
      The management options range from observation to emergency splenectomy. Computed
      tomography scan is the most important imaging modality to diagnose splenic
      injury. Early recognition and appropriate management is of paramount importance
      in the management of this condition. A high index of suspicion in a patient with
      persistent abdominal pain after colonoscopy is key especially when a perforated
      viscous is ruled out. This article outlines the clinical presentation of splenic
      injury after colonoscopy and delineates a management algorithm.

PMID- 21886053
TI  - A paradigm shift in the outpatient approach to liver function tests.
AB  - The American Gastroenterological Association (2002), Canadian Medical Association
      (2005), and the Centers for Disease Control and Prevention (2006) released
      guidelines to screen patients with mild elevations of liver enzymes for hepatitis
      B and hepatitis C. Mildly elevated liver enzymes were defined as less than five
      times the upper limit of normal, but above the normal reference range. The
      rationale for this recommendation was based on many factors including cost
      effectiveness, lab variation, and ultimately, for better patient care.Chronic
      hepatitis B and C have values of transaminases that fluctuate between normal and
      mildly abnormal. Screening patients with even mild elevations of transaminases
      allows many chronic hepatitis patients to be diagnosed early in the course of
      their disease. Diagnosing these patients early in their disease course leads to
      better treatment response, decreased progression to cirrhosis, lower viral loads
      leading to decreased incidence of extrahepatic manifestations, prevention of
      hepatocellular carcinoma, and decreased likelihood of liver transplantation.There
      are organizations which recommend discontinuing hepatotoxic medications such as
      acetaminophen or nonsteroidal anti-inflammatory drugs and reevaluating the
      patient in three months. However, this recommendation misses a number of
      hepatitis patients for the reasons aforementioned. The obesity epidemic has
      clouded the diagnosis of hepatitis B/C as patients that have obesity, diabetes
      mellitus, and metabolic syndrome are not being screened due the presumptive
      diagnosis of nonalcoholic fatty liver disease.Not screening patients in the
      setting of obesity is not cost-effective and also leads to increased morbidity,
      as we will discuss in this manuscript. Additionally, it has been proven in the
      literature that it is more cost-effective to screen for hepatitis B/C in high
      prevalence areas, than to reassess the patient months later, and potentially miss
      a diagnosis of hepatitis B/C. The overall goal of this study is to increase
      screening awareness of patients with mild transaminitis elevations through
      publication in order to diagnose patients with hepatitis B and C prior to the
      development of chronic liver disease.

PMID- 21886054
TI  - Carotid artery examination, an important tool in patient evaluation.
AB  - Examination of the arteries is an age old medical tradition. Examination of the
      carotid artery is of unique importance because it is an easily accessible large
      artery. Through the methods of inspection, palpation, and auscultation, carotid
      artery examination gives clinicians important diagnostic clues about the health
      and disease of the patient. Inspection and palpation of the carotid give insight
      into left ventricular systolic function and distinguish types of valvular heart
      disease. Auscultation identifies patients with high-risk atherosclerosis. In most
      cases carotid examination is neither sensitive nor specific, but in the correct
      clinical context it offers important evidence leading to specific diagnoses and
      treatment. In this review, we discuss the examination of the carotid artery under
      normal conditions and describe how abnormalities in the carotid artery
      examination are indicators of disease.

PMID- 21886055
TI  - Physician perspective on propoxyphene as a potentially inappropriate medication
      in Tennessee.
AB  - Medicare Part D data from the Quality Improvement Organization's 9th Statement of
      Work drug safety indicator project under the direction of the Centers for
      Medicare & Medicaid Services define the potentially inappropriate medications
      (PIMs) list for Tennessee. These data reveal propoxyphene as the main contributor
      to the state's PIM rate. In Tennessee, PIM and drug-drug interaction (DDI) rates
      indicate propoxyphene as the most prescribed medication among elderly patients
      despite decades of attention for potentially adverse effects. During this
      project, physicians agreed that PIM rates are too high, but disagreed in approach
      preference, i.e., administrative limits and bans versus a proactive educational
      approach. Physicians were interested in participating in quality improvement by
      using individual pharmacy data to influence prescribing patterns. Exploring
      alternatives in research and survey, a potential and reachable point of
      intervention was found, a prescribing paradigm proposed by researchers to improve
      outcomes by reducing adverse effects in minimizing PIMs and DDIs.

PMID- 21886056
TI  - Hantavirus pulmonary syndrome: need for prevention and early diagnosis.

PMID- 21886057
TI  - More adverse neurological consequences of metformin-induced vitamin B12
      deficiency.

PMID- 21886060
TI  - Effect of hepatitis C virus infection on the left ventricular systolic and
      diastolic functions.
AB  - BACKGROUND: Hepatitis secondary to infection with the hepatitis C virus (HCV) is
      one of the most common causes of viral hepatitis worldwide. Multiple extrahepatic
      manifestations of HCV infection have been recognized. Dilated and hypertrophic
      cardiomyopathy associated with HCV infection have been recently described in the
      literature; however, the effect of HCV infection on the left ventricular systolic
      and diastolic functions is unknown. Therefore, in this study we aimed to examine
      left ventricular systolic and diastolic functions in HCV patients. METHODS AND
      RESULTS: The study included 50 anti-HCV positive patients and 50 persons for
      control groups. We performed transthorasic echocardiography and P-wave analysis
      on all participants. We compared left ventricle diastolic parameters, left
      ventricle ejection fraction, and P-wave dispersion (Pd) between these two groups.
      In the group with anti-HCV positivity, the ratio of E/A was found to be lower
      (1.2 +/- 0.7 and 1.37 +/- 0.6, P = 0.003); the ratio of E/Em was found to be
      higher (7.6 +/- 1.51 and 6.8 +/- 1.72, P = 0.0001). Maximum P-wave duration
      (Pmax) and Pd were higher in the patient group (99.3 +/- 8 and 82.4 +/- 7.8, P =
      0.004; 44.1 +/- 0.9 and 25.3 +/- 1.5, P = 0.001). No other statistically
      significant difference was found between the two groups with regard to the left
      ventricle systolic and diastolic parameters. CONCLUSION: Our findings show that
      HCV infection may be associated with left ventricular systolic and diastolic
      dysfunction and cardiac arrhythmias.

PMID- 21886061
TI  - Effect of periodontal treatment on lipoproteins levels in plasma in patients with
      periodontitis.
AB  - OBJECTIVES: Recent epidemiological studies have shown that individuals with
      periodontitis have a significantly increased risk of developing coronary heart
      disease. In addition to conventional risk factors, dyslipidemia may be associated
      with this increased risk. METHODS: We measured concentration of lipids in
      patients with moderate to severe periodontitis before and 3, 6 and 12 months
      after local periodontal treatment. A total of 50 participants with periodontitis
      and 25 participants without periodontitis were included in the analyses.
      Lipoproteins were measured by using serological analyses of the Central
      Biochemical Laboratory in Clinical Center in Nis. Periodontal health indicators
      included the plaque index, gingival bleeding index, and periodontal disease
      status (defined by pocket depth and attachment loss). Patients were non
      surgically treated with mechanical debridement of calculus once a week for 1
      month. RESULTS: The results show a significant relation between indicators of
      poor periodontal status and serum level lipoproteins. Periodontal therapy
      resulted in a significant reduction of local inflammation and tissue destruction
      as reflected in reduced pocket depth and reduced bleeding indices. The levels of
      lipoproteins after therapy seemed to be lower than those reported before
      treatment in patients with periodontitis compared with healthy ones. Lipoproteins
      were significantly decreased after treatment (P < 0.005) except high-density
      lipoprotein cholesterol which was not significantly reduced (P > 0.05).
      CONCLUSION: This pilot study shows that periodontal disease significantly affects
      the serum levels of lipoproteins and suggests that following successful
      periodontal treatment decreases serum lipid concentration. This study suggests
      also that lipoproteins are possible intermediate factors that may link
      periodontal disease to elevated cardiovascular risk.

PMID- 21886062
TI  - Socioeconomic disparities in prostate cancer mortality and the impact of
      geographic scale.
AB  - OBJECTIVE: To examine socioeconomic disparities in prostate cancer mortality and
      to assess the scale effect on the results of the disparity analysis. METHODS:
      Using prostate cancer mortality data (N = 14,036) of Texas from 1996 to 2004,
      this study examines the variations of socioeconomic disparities in prostate
      cancer mortality across different geographic scales. Age-adjusted odds ratios are
      employed to reveal the disparities by single and composite socioeconomic
      indicators at county, census tract, and block group levels. RESULTS: The analysis
      shows that (1) disparities in prostate cancer mortality are significant for most
      socioeconomic indicators, (2) area-level socioeconomic indicators tend to reveal
      a less extent of disparity than individual-level indicators do, and (3)
      socioeconomic disparities in prostate cancer mortality at the census tract and
      block group levels are similar to each other but are completely different from
      those at the county level. CONCLUSION: The selection of geographic scale and
      socioeconomic indicators affects the results of socioeconomic disparity analysis
      in prostate cancer mortality. Most census tract and block group level
      socioeconomic indicators are appropriate for analyzing disparities in prostate
      cancer mortality. County level socioeconomic indicators should be avoided if
      possible.

PMID- 21886063
TI  - Socioeconomic disparities in prostate cancer mortality.

PMID- 21886064
TI  - Prevalence, incidence, and recurrence of oral lesions among HIV-infected patients
      on HAART in Alabama: a two-year longitudinal study.
AB  - OBJECTIVE: Our aim was to quantify prevalence, incidence, and recurrence of oral
      lesions (OL) among a population in the Southeast. METHODS: A retrospective study
      based on chart review was conducted among patients (n = 744) who were >=19 years
      of age and initiated highly active antiretroviral therapy (HAART) between January
      2000 and June 2006 at the University of Alabama at Birmingham (UAB) 1917 Clinic.
      Patients' laboratory data and oral conditions were recorded for 2 years after
      enrollment into the study. RESULTS: During 2 years of follow-up, the period
      prevalence of individuals experienced at least one OL was 35.6% (266/744). Among
      all of the 374 episodes of OL, 183 were new cases, while 57 were recurrences. The
      OL person-visit incidence rate was 0.02 per 100 person-visits. Oropharyngeal
      candidiasis (OPC) was the most frequent manifestation in terms of period
      prevalence (74.9%) with a person-visit incident rate of 0.01 per 100 person
      visits. CONCLUSIONS: Patients undergoing HAART continue to be affected by HIV
      related oral conditions, especially OPC. These results clearly indicate that OL
      during HIV infection are still highly prevalent in spite of the improvements in
      medical care and the availability of HAART.

PMID- 21886065
TI  - Eliminating disparities in hypertension care for Hispanics and blacks using a
      heart failure disease management program.
AB  - OBJECTIVES: This study assessed if patients enrolled in a heart failure disease
      management program (HFDMP) reach the JNC VII target goals for blood pressure (BP)
      control, eliminate disparities in hypertension control by race/ ethnicity and the
      impact BP control has on survival. METHODS: Patients (N = 898) with an ejection
      fraction <40% were enrolled into two HFDMPs and screened for hypertension,
      defined as BP > 130/80. RESULTS: Mean baseline systolic BP (SBP) 132 +/- 25.5 mm
      Hg and diastolic BP (DBP) 79 +/- 16.8 mm Hg. Final mean SBP decreased to 129.6 mm
      Hg, DBP 77.6 mm Hg. Whites had the highest rate of achieving BP goals. Mortality
      reduction was associated with minority race, history of hypertension, increase
      ejection fraction and statin use. CONCLUSION: HFDMPs are an effective way to
      reduce BP in hypertensive patients. Disparities by race and ethnicity were not
      seen after adjustment for disease modifiers. There was no mortality difference in
      those who reached BP goal.

PMID- 21886066
TI  - Additional therapeutic effect of balneotherapy in low back pain.
AB  - OBJECTIVES: Balneotherapy has been widely used for treatment of chronic low back
      pain recently. However there are only a few clinical controlled trials on
      balneotherapy. The aim of the present study was to evaluate the effects of
      balneotherapy in patients with chronic low back pain. METHODS: Sixty patients
      with lumbar spondylosis were included in the study. In Group 1, patients received
      both balneotherapy and physiotherapy and in Group 2, patients received only
      physiotherapy for three weeks. The intensity of the pain was evaluated by Visual
      Analog Scale (VAS) and functional disability was scored according to Revised
      Oswestry Index (ROI). Spinal mobility was assessed by the Schober and lateral
      flexion tests. Variables were evaluated before and after the three weeks of
      treatment. RESULTS: The groups were comparable regarding age (P = 0.970) and sex
      (P = 0.357). There was no statistically significant difference between the two
      groups for baseline VAS (P = 0.838), Schober test (P = 0.226), and right (P =
      0.642) and left (P = 0.674) lateral flexion measurements, and ROI scores (P =
      0.798). At the end of the therapy, all clinical parameters significantly improved
      in patients in both of the groups (P < 0.05). VAS, Schober test, and ROI scores
      after the therapy were clearly superior in Group 1 in comparison to Group 2 (P <
      0.05). CONCLUSION: The results of the present study reiterate that besides
      conventional physiotherapy, balneotherapy may be effective in the treatment of
      patients with chronic low back pain.

PMID- 21886068
TI  - Knowledge of osteoporosis among men in the primary care setting.
AB  - OBJECTIVES: Osteoporosis has been often viewed as a disease affecting women;
      however, men are at risk for osteoporosis, and the mortality after hip fracture
      in men older than 75 years of age is significantly higher than in women. We aimed
      to assess knowledge of osteoporosis and its risk factors in men. METHODS: A
      questionnaire assessing knowledge of osteoporosis was presented to 136 male
      patients randomly in Internal Medicine and Family Practice clinics at Saint
      Joseph Hospital. RESULTS: A total of 136 men agreed to fill in the questionnaire.
      Only 130 patients who completed the entire questionnaire were included in the
      data analysis. Twenty-three percent of men surveyed had never heard about
      osteoporosis. Thirty-nine percent were unaware that osteoporosis is directly
      responsible for disabling hip fractures. Sixty-seven percent did not know that a
      potential outcome of hip fracture is death. Only 38% recognized that smoking is a
      risk factor, 20% knew that excessive caffeine intake can put them at risk, and
      35% realized that excessive alcohol intake is a risk factor. Only 21% could
      correctly identify the calcium-rich foods among the choices. There was a positive
      relationship (P < 0.05) between receiving an official discussion with a physician
      regarding osteoporosis and the actual score on the "knowledge of osteoporosis"
      questionnaire. CONCLUSION: A significant percentage of men are unaware of the
      complications and risk factors for osteoporosis. Receiving educational
      information about osteoporosis from a physician should be considered at an early
      stage, especially for those patients with modifiable risk factors.

PMID- 21886067
TI  - Second-line levofloxacin-based triple therapy's efficiency for Helicobacter
      pylori eradication in patients with peptic ulcer.
AB  - OBJECTIVES: First-line standard eradication efficacy with lansoprazole,
      amoxicillin and clarithromycin regressed over 10 years. The aim of this study was
      to evaluate the efficacy and tolerability of a levofloxacin-based regimen in
      patients with peptic ulcer after failure of the standard first-line H.pylori
      eradication therapy in a country with a high rate of infection. METHODS: A total
      of 91 peptic ulcer patients who were diagnosed H.pylori positive proven by rapid
      urease test and histology between November 2005 to March 2008 were given
      lansoprazole 30 mg bid, amoxicillin 1 g bid and clarithromycin 500 mg bid (LAC)
      for 14 days. After three months from the first line eradication treatment
      omeprazole 20 mg bid, levofloxacin 500 mg bid, amoxicillin 1 g bid (OLA) 7 day
      treatment regimen was recommended as a second-line therapy for 37 patients who
      failed at first-line standard triple therapy. RESULTS: Eradication rates for LAC
      regimen were found to be 57.14% (52/91) for intention to treat and 58.42% (52/89)
      for per protocol analysis. Eradication rates for OLA regimen were found to be
      37.83% (14/37) for ITT and 41.17% (14/34) for PP analysis. CONCLUSION: OLA
      regimen eradication rate was successful only in 40% of patients who failed in the
      first-line eradication. New eradication treatment strategies must be performed,
      at least in Turkey.

PMID- 21886069
TI  - Should all patients with pulmonary hypertension undergo HIV serologic testing?
AB  - OBJECTIVES: To evaluate the yield of screening patients with pulmonary
      hypertension (PH) for human immunodeficiency virus (HIV) infection. METHODS: We
      retrospectively reviewed the records of consecutive patients with PH seen at our
      institution from July 1992 to November 2008. We assessed HIV risk factors and
      history of HIV. We estimated the proportion of patients who tested positive for
      HIV. RESULTS: We identified 445 patients with PH who had serologic testing for
      HIV antibody. The mean age was 63 years, and 66% were women. Of these patients,
      224 (50%) were in World Health Organization diagnostic group I, pulmonary
      arterial hypertension (PAH). Only 1 patient (0.2%; 95% confidence interval, 0.0%
      1.2%) was positive for HIV, and this was the only patient who had a known history
      of HIV infection. Ten other patients (2.2%) had risk factors for HIV infection
      but had negative serologic results. The patient who tested positive for HIV had
      PAH, yielding an estimated prevalence of positive HIV testing in that subgroup of
      0.4% (95% confidence interval, 0.0%-2.5%); 6 other patients with PAH (2.7%) had
      risk factors for HIV but negative serology. CONCLUSIONS: To our knowledge, this
      is the first study examining the yield of screening patients with PH for HIV
      using serologic testing. Of the 445 patients tested, only 1 patient was positive
      for HIV. This patient was known to have risk factors for and exposure to HIV.
      Patients with PAH should be assessed for risk factors for HIV before testing for
      HIV in low-risk populations.

PMID- 21886070
TI  - Incidence and impact of false-positive urine pneumococcal antigen testing in
      hospitalized patients.
AB  - OBJECTIVES: Immunochromatographic urine pneumococcal antigen testing (ICT) has
      become a common diagnostic tool for those presenting with possible invasive
      pneumococcal disease. The incidence and clinical impact of ICT false-positivity
      on hospitalized patients has not been assessed outside of specific patient
      subpopulations. ICT performance needs to be assessed in a real-world clinical
      setting. This study aims to describe the incidence and clinical impact of ICT
      false-positivity in a hospital setting over a 19-month period. METHODS: A
      retrospective cohort study was performed to assess the incidence of false
      positive (FP) ICT among hospitalized patients from November 21, 2007 to June 30,
      2009. The primary objective was to describe the incidence of FP ICT results. The
      secondary objective was to describe what clinical impact, if any, could be
      attributed to FP ICT results. RESULTS: During the study period, 52 positive ICT
      results were obtained, of which 5 (9.6%) were deemed falsely positive.
      Interestingly, two of the 5 FP results were from patients who had received 23
      valent pneumococcal vaccine (PPV) in the 2 days prior to ICT. The management of
      all 5 patients was impacted by the FP results through unnecessary antimicrobial
      treatment and/or deferral of further clinical evaluation. CONCLUSION: Health care
      providers should be aware of the potential for ICT FP and should order and
      interpret these tests within an informed clinical framework.

PMID- 21886071
TI  - Student-led rural health fairs: attempting to improve medical education and
      access to health care.
AB  - OBJECTIVES: Residents of rural communities, especially in the Southeast, have
      decreased access to health care. Ensuring medical students receive adequate
      exposure to their issues is complicated by the urban location of most schools. We
      describe health fairs conducted in rural communities to suggest how having
      medical students use screening tools can identify patients with risk factors for
      disease which can offer students the opportunity to learn about rural health
      issues through patient counseling. METHODS: The Mitchell Wolfson Sr. Department
      of Community Service, a University of Miami Miller School of Medicine student-led
      organization, conducts fairs at four sites throughout the rural Florida Keys.
      Medical students, under the supervision of attending physicians, offer screening
      and preventive health services including risk factor screening for cardiovascular
      disease, ophthalmological exams, dermatologic exams, osteoporosis screening, and
      female exams with pap smears. These fairs were reviewed. RESULTS: In the past
      three years, 1694 unique patients were seen. Many lacked a primary care provider
      (46%) or health insurance (43%) and were provided screening for several disorders
      including cardiovascular disease risk factors (hypertension, diabetes,
      dyslipidemia, and obesity). Screening revealed that many patients (41%) had
      multiple markers of elevated cardiovascular disease risk. This provided
      experiences to more than 200 students each year. CONCLUSION: Fairs provide
      medical students exposure to rural health issues through the valuable opportunity
      of using risk factor screening tools and counseling. This provides valuable
      information to patients of rural communities. Future research should examine how
      fairs influence student knowledge and attitudes toward rural health and affect
      health outcomes.

PMID- 21886072
TI  - Well-child care in infancy and emergency department use by South Carolina
      Medicaid children birth to 6 years old.
AB  - OBJECTIVES: This analysis tests the hypothesis that children enrolled in Medicaid
      with the recommended early and periodic screening, diagnosis and treatment
      (EPSDT) visits in the first 24 months utilize fewer emergency department (ED)
      services birth to 6 years old than children with fewer visits. METHODS: Data
      represent all health encounters for a 3-year birth cohort of South Carolina
      children continuously enrolled in Medicaid from birth to 6 years old (n =
      18,512). The association between receiving the American Academy of Pediatrics
      recommended EPSDT visits and other health service utilization is examined.
      RESULTS: Children with the recommended EPSDT visits had a greater adjusted rate
      of sick-child visits with a primary care provider (rate ratio, 1.62; 95% CI 1.50-
      1.76) and a lower adjusted rate of ED visits for ambulatory care-sensitive
      conditions (rate ratio, 0.88; 95% CI, 0.81-0.95). CONCLUSION: Recommended EPSDT
      use in infancy may be associated with a shift in health care from the ED to the
      office setting by children enrolled in Medicaid in the first six years of life.

PMID- 21886073
TI  - Iron insufficiency and hypovitaminosis D in adolescents with chronic fatigue and
      orthostatic intolerance.
AB  - OBJECTIVES: More than 10% of adolescents suffer from severe fatigue and/or
      orthostatic intolerance. Adult studies show correlations between iron
      insufficiency and fatigue as well as between hypovitaminosis D and non-specific
      pain. We sought to determine whether there were correlations between nutritional
      factors (iron status, and serum vitamin D levels) and chronic ill health.
      METHODS: We reviewed records of 188 adolescents with symptoms of fatigue and/or
      orthostatic intolerance and who underwent autonomic reflex screening. RESULTS: Of
      the 188 patients, 130 patients (69%) had excessive postural tachycardia (PT) with
      a heart rate (HR) change of >=30 bpm. 62 patients (47%, n = 131) had iron
      insufficiency with low iron stores, and 29 patients (22%, n = 131) were iron
      deficient. HR change did not correlate to ferritin level (P = 0.15). 21 patients
      (22%, n = 95) had hypovitaminosis D (25-hydroxyvitamin D <=20 ng/mL). There was a
      significant association with hypovitaminosis D and orthostatic intolerance (P =
      0.024). CONCLUSION: In patients presenting with chronic fatigue and/or
      orthostatic intolerance, low ferritin levels and hypovitaminosis D are common,
      especially in patients with PT.

PMID- 21886074
TI  - Place in therapy for liraglutide and saxagliptin for type 2 diabetes and FDA
      liraglutide warning.

PMID- 21886075
TI  - Tetanus: a review.
AB  - Tetanus is a preventable illness occurring worldwide with a high mortality,
      mostly affecting neonates in developing countries. Effects are toxin mediated and
      the diagnosis is clinical. Antibiotics, antitoxin, immunoglobulin and wound care
      are the mainstays of management.

PMID- 21886076
TI  - Remembering September 11, 2001, and the implications for physician disaster
      preparedness.

PMID- 21886077
TI  - A surgeon's journey.

PMID- 21886078
TI  - The computerized patient and the art of bedside diagnosis.

PMID- 21886079
TI  - CA-125 level is associated with right ventricular echocardiographic parameters in
      patients with COPD.
AB  - OBJECTIVE: A few studies have shown that elevated CA-125 levels are associated
      with chronic obstructive pulmonary disease (COPD). However, there are no data
      concerning the associaton between serum CA-125 levels and right ventricular (RV)
      function in COPD patients. This study aimed to evaluate the relationship between
      CA-125 level and RV echocardiographic parameters in COPD patients. METHODS: Fifty
      two patients with COPD (39 male/13 female, mean age 68.9 +/- 5.7 years) were
      studied. The control group consisted of 30 age-sex matched healthy volunteers (23
      male/7 female, mean age 64.2 +/- 6.3 years). Patients were divided into two
      subgroups: patients without pulmonary hypertension (group I, n = 25) and with
      pulmonary hypertension (group II, n = 27). Conventional echocardiographic
      parameters, tissue Doppler imaging (TDI) and CA-125 level measurements were
      performed in all subjects. RESULTS: Patients in group II had significantly higher
      CA-125 levels than those in group I and controls (P < 0.01). CA-125 levels in
      group I were also higher than control group (P < 0.05). CA-125 levels were
      correlated with left ventricle E/A ratio, systolic pulmonary artery pressure
      (sPAP), RV myocardial performance index, and RV fractional area change (r = 0.37,
      0.56, 0.34, and -0.42, respectively, all with P < 0.05). There was an independent
      correlation between CA-125 levels and sPAP values (beta = 0.76, P < 0.001).
      CONCLUSIONS: Our results show an independent correlation between CA-125 levels
      and systolic pulmonary artery pressure in COPD patients. The clinical utility of
      these results at this point in time is unknown and deserves future research.

PMID- 21886080
TI  - Evaluation of pain management documentation.
AB  - OBJECTIVES: Accurate and consistent documentation of pain management, including
      patient responses regarding improvement in pain scores, is essential for
      improving patient care. The objective of the project was to evaluate the current
      prescribing patterns and to review the current documentation for opioid-managed,
      chronic pain patients in an academic continuity of care medicine clinic. METHODS:
      Retrospective data were extracted from currently managed adult, opioid patients
      to evaluate prescribing patterns and to review documentation processes. RESULTS:
      Results reveal inconsistent to absent documentation with most patients receiving
      prescriptions from multiple providers. Oxycodone/acetaminophen was the most
      frequently prescribed analgesic. CONCLUSION: The results of this evaluation
      highlight the opportunity for educational intervention and the development of a
      structured, institution-specific guideline for prescribing and documenting pain
      management.

PMID- 21886081
TI  - Communication skills and chronic pain management.

PMID- 21886082
TI  - Can a model predictive of vitamin D status be developed from common laboratory
      tests and demographic parameters?
AB  - OBJECTIVES: Vitamin D deficiency is highly prevalent and has been linked to
      increased morbidity and mortality. There has been an increase in testing for
      vitamin D with a concomitant increase in costs. While individual factors are
      significantly linked to vitamin D status, prior studies have not yielded a model
      predictive of vitamin D status or 25(OH)D levels. The purpose of this
      investigation was to determine if a prediction model of vitamin D could be
      developed using extensive demographic data and laboratory parameters. METHODS:
      Patient data from 6 Veterans Administration Medical Centers were extracted from
      medical charts. RESULTS: For the 14,920 available patients, several factors
      including triglyceride level, race, total cholesterol, body mass index, calcium
      level, and number of missed appointments were significantly linked to vitamin D
      status. However, these variables accounted for less than 15% of the variance in
      vitamin D levels. While the variables correctly classified vitamin D deficiency
      status for 71% of patients, only 33% of those who were actually deficient were
      correctly identified as deficient. CONCLUSION: Given the failure to find a
      sufficiently predictive model for vitamin D deficiency, we propose that there is
      no substitute for laboratory testing of 25(OH)D levels. A baseline vitamin D 3
      daily replacement of 1000-2000 IU initially with further modification based on
      biannual testing appears to factor in the wide variation in dose response
      observed with vitamin D replacement and is especially important in high-risk
      groups such as ethnic minorities.

PMID- 21886083
TI  - Racial disparities in pediatric intensive care unit admissions.
AB  - OBJECTIVES: Racial disparities in therapies and outcomes in adult and neonatal
      ICUs are well documented; however, little is known regarding racial disparities
      in pediatric intensive care unit (PICU). Our objective was to determine whether
      racial disparities exist in the admission of critically ill children to the PICU.
      METHODS: We retrospectively analyzed admissions to a PICU in a tertiary care
      pediatric hospital. Summarized demographic data was analyzed from the county
      health department. RESULTS: Of the 4676 admissions to the PICU between January 1,
      1997 and December 31, 1999, 1030 children were <48 months of age, lived in Shelby
      County, TN, and were either African American (789, 76.6%) or non-Hispanic white
      (241, 23.4%). The surrounding county was comprised of approximately 58% African
      American and 41% non-Hispanic white children <= 48 months of age. A history of
      premature birth was more common in African American children than non-Hispanic
      white children (46.8% vs. 32.8%; P < 0.0001). Mortality was 5.7% overall and was
      not significantly different between African Americans and non-Hispanic whites but
      was higher for those children with a history of premature birth (4.6% vs. 7.1%, P
      < 0.026). The overall relative risk of admission to the PICU for African American
      children was 2.12 (95% CI, 1.66-2.74), for African American children with a
      history of premature birth was 1.44 (95% CI, 0.96-2.21), and for full-term
      African American children was 1.82 (95% CI, 1.33 -2.49). CONCLUSIONS: Racial
      differences in admission to the PICU exist with African American children having
      a greater risk for PICU admission than non-Hispanic white children.

PMID- 21886084
TI  - Innovations in faculty development: study of a research assistance unit designed
      to assist clinician-educators with research.
AB  - OBJECTIVES: At a mid-sized community medical school, research was not
      traditionally strong. Faculty members cited lack of infrastructure support as a
      significant research barrier. In response, the regional dean developed and funded
      a research assistance unit (RAU) in 2006 to provide administrative and
      statistical support to junior faculty beginning their research programs. This
      study examined the efficacy of the RAU from 2006-2008. METHODS: The authors
      reviewed RAU records for number and types of projects; time from initial contact
      to IRB approval; type and hours of assistance; number of abstracts and
      publications resulting from RAU-sponsored projects; number and rank of faculty,
      student, and resident researchers; and cost of RAU operations. A satisfaction
      survey was given to faculty members who completed projects. RESULTS: The RAU
      provided assistance with 68 projects involving a total of 36 faculty members, 34
      residents, and 21 medical students, resulting in 12 published abstracts and/or
      manuscripts. RAU administrative assistance averaged 7 hours per project.
      Statistical assistance was provided for 21 projects and averaged 13 hours.
      Participation in clinical research by faculty rose from 8% to 32%, by residents
      from 24% to 31%, and by medical students from 22% to 43%. Of surveyed faculty,
      92% rated their experience with the RAU as satisfactory or very satisfactory.
      Cost averaged $128,000 yearly. CONCLUSIONS: The creation of a staff support unit
      resulted in an increase in research by faculty, residents, and students.

PMID- 21886085
TI  - The more you know: what is the impact of research experience?

PMID- 21886086
TI  - Association of doxycycline prescriptions and tick-related emergency department
      visits in North Carolina.
AB  - OBJECTIVES: To compare the seasonal frequency of doxycycline prescriptions with
      tick-related emergency department (ED) visits in North Carolina, and to determine
      if doxycycline prescriptions are associated in time with an increase in the
      number of ED visits for a tick-related patient complaint or a subsequent
      diagnosis of a tick-borne infection. METHODS: Aggregate monthly counts of total
      dispensed doxycycline prescriptions for each North Carolina Piedmont Metropolitan
      Statistical Area (MSA) were compared with the proportions of tick-related ED
      visits from August 2007 through July 2009. RESULTS: Epidemic curves of tick
      related ED visits for each of the 6 MSAs were characterized by increased
      frequency in the spring and summer months followed by a decline in the fall.
      However, the pattern of doxycycline prescriptions varied by MSA. Doxycycline
      prescriptions in Durham-Chapel Hill and Raleigh-Cary MSAs increased in the spring
      and summer, while for the 4 other Piedmont MSAs there was no consistent or
      pronounced spring-summer increase. CONCLUSION: Doxycycline prescription use did
      not always correlate well with suspected tick activity in North Carolina.
      Therefore, doxycycline prescription use cannot necessarily be used as a surrogate
      measure of tick activity for infectious disease surveillance until the reasons
      for this variability are better understood.

PMID- 21886087
TI  - Cannabinoid hyperemesis syndrome: literature review and proposed diagnosis and
      treatment algorithm.
AB  - Cannabinoid hyperemesis syndrome (CHS) is characterized by cyclic vomiting and
      compulsive bathing behaviors in chronic cannabis users. Patients are typically
      diagnosed with CHS only after multiple and extensive medical evaluations,
      consequently without a clear etiology of their symptoms or treatment plan leading
      to symptomatic improvement. Increased healthcare provider awareness of CHS as a
      cause of nausea, vomiting, and abdominal pain coupled with an attentiveness to
      focused history taking-especially noting symptomatic improvement with prolonged
      exposure to hot showers or baths-can lead to effective treatment through cannabis
      cessation. We propose a diagnosis and treatment algorithm for physicians to
      follow when evaluating patients presenting with nausea, vomiting, and abdominal
      pain who are suspected to suffer from CHS.

PMID- 21886088
TI  - Emerging role of chronic cannabis usage and hyperemesis syndrome.

PMID- 21886090
TI  - Mechanisms other than atherosclerosis in the partnership between chlamydia and
      stroke.

PMID- 21886091
TI  - Atrial fibrillation in cancer patients: an underrecognized condition.

PMID- 21886092
TI  - Liver biopsy in hepatocellular cancer: how closely do we adhere to the
      guidelines?

PMID- 21886093
TI  - Mathematical evaluation of the amino acid and polyphenol content and antioxidant
      activities of fruits from different apricot cultivars.
AB  - Functional foods are of interest because of their significant effects on human
      health, which can be connected with the presence of some biologically important
      compounds. In this study, we carried out complex analysis of 239 apricot
      cultivars (Prunus armeniaca L.) cultivated in Lednice (climatic area T4), South
      Moravia, Czech Republic. Almost all previously published studies have focused
      only on analysis of certain parameters. However, we focused on detection both
      primary and secondary metabolites in a selection of apricot cultivars with
      respect to their biological activity. The contents of thirteen biogenic alpha-L
      amino acids (arginine, asparagine, isoleucine, lysine, serine, threonine, valine,
      leucine, phenylalanine, tryptophan, tyrosine, proline and alanine) were
      determined using ion exchange chromatography with UV-Vis spectrometry detection.
      Profile of polyphenols, measured as content of ten polyphenols with significant
      antioxidant properties (gallic acid, procatechinic acid, p-aminobenzoic acid,
      chlorogenic acid, caffeic acid, vanillin, p-coumaric acid, rutin, ferrulic acid
      and quercetrin), was determined by high performance liquid chromatography with
      spectrometric/electrochemical detection. Moreover, content of total phenolics was
      determined spectrophotometrically using the Folin-Ciocalteu method. Antioxidant
      activity was determined using five independent spectrophotometric methods: DPPH
      assay, DMPD method, ABTS method, FRAP and Free Radicals methods. Considering the
      complexity of the obtained data, they were processed and correlated using
      bioinformatics techniques (cluster analysis, principal component analysis). The
      studied apricot cultivars were clustered according to their common biochemical
      properties, which has not been done before. The observed similarities and
      differences were discussed.

PMID- 21886094
TI  - Mortality in preterm infants with respiratory distress syndrome treated with
      poractant alfa, calfactant or beractant: a retrospective study.
AB  - OBJECTIVE: The objective of this study is to compare all-cause in-hospital
      mortality in preterm infants with respiratory distress syndrome (RDS) treated
      with poractant alfa, calfactant or beractant. STUDY DESIGN: A retrospective
      cohort study of 14 173 preterm infants with RDS, treated with one of three
      surfactants between 2005 and 2009, using the Premier Database was done.
      Multilevel, multivariable logistic regression modeling, adjusting for patient-
      and hospital-level factors was performed. RESULT: Calfactant treatment was
      associated with a 49.6% greater likelihood of death than poractant alfa (odds
      ratio (OR): 1.496, 95% confidence interval (CI): 1.014-2.209, P=0.043). Beractant
      treatment was associated with a non-significant 37% increase in mortality,
      compared with poractant alfa (OR: 1.370, 95% CI: 0.996-1.885, P=0.053). No
      differences in mortality were observed between calfactant and beractant treatment
      (OR: 1.092, 95% CI: 0.765-1.559, P=0.626). CONCLUSION: Poractant alfa treatment
      for RDS was associated with a significantly reduced likelihood of death when
      compared with calfactant and a trend toward reduced mortality when compared with
      beractant.

PMID- 21886095
TI  - Generation of transgene-free human induced pluripotent stem cells with an
      excisable single polycistronic vector.
AB  - The generation of induced pluripotent stem cells (iPSCs) devoid of permanently
      integrated reprogramming factor genes is essential to reduce differentiation
      biases and artifactual phenotypes. We describe a protocol for the generation of
      human iPSCs using a single polycistronic lentiviral vector (pLM-fSV2A)
      coexpressing OCT4, SOX2, KLF4 and c-MYC; this is flanked by two loxP sites in its
      long terminal repeats (LTRs). Human iPSC lines are established with an efficiency
      of up to 1% and screened to select single or low vector copy lines. To deal with
      potential insertional mutagenesis, the vector integrations are then mapped to the
      human genome. Finally, the vector is excised by transient expression of Cre
      recombinase (coexpressed with mCherry) through an integrase-deficient lentiviral
      vector. Vector-excised iPSC lines maintain all characteristics of pluripotency.
      This protocol can be used to efficiently derive transgene-free iPSCs from many
      different starting cell types in approximately 12-14 weeks.

PMID- 21886096
TI  - Derivation of genetically modified human pluripotent stem cells with integrated
      transgenes at unique mapped genomic sites.
AB  - Many applications in human pluripotent stem cell (PSC) research require the
      genetic modification of PSCs to express a transgene in a stable and dependable
      manner. Random transgene integration commonly results in unpredictable and
      heterogeneous expression. We describe a protocol for the derivation of clonal
      populations of human embryonic stem cells or induced pluripotent stem cells
      (iPSCs) expressing a transgene from a single copy of an integrated lentiviral
      vector that is mapped to the genome. Using optimized transduction conditions,
      followed by single-cell subcloning and a round of antibiotic selection, we find
      that approximately half of the colonies retrieved contain a single vector copy.
      After expansion, the majority of these are confirmed to be clonal. The
      vector/genomic DNA junction is sequenced and the unique integration site is
      mapped to the genome. This protocol enables the efficient derivation of
      genetically modified PSCs containing an integrated transgene at a known genomic
      site in ~7 weeks.

PMID- 21886097
TI  - Quantitative prediction of cellular metabolism with constraint-based models: the
      COBRA Toolbox v2.0.
AB  - Over the past decade, a growing community of researchers has emerged around the
      use of constraint-based reconstruction and analysis (COBRA) methods to simulate,
      analyze and predict a variety of metabolic phenotypes using genome-scale models.
      The COBRA Toolbox, a MATLAB package for implementing COBRA methods, was presented
      earlier. Here we present a substantial update of this in silico toolbox. Version
      2.0 of the COBRA Toolbox expands the scope of computations by including in silico
      analysis methods developed since its original release. New functions include (i)
      network gap filling, (ii) (13)C analysis, (iii) metabolic engineering, (iv) omics
      guided analysis and (v) visualization. As with the first version, the COBRA
      Toolbox reads and writes systems biology markup language-formatted models. In
      version 2.0, we improved performance, usability and the level of documentation. A
      suite of test scripts can now be used to learn the core functionality of the
      toolbox and validate results. This toolbox lowers the barrier of entry to use
      powerful COBRA methods.

PMID- 21886098
TI  - Assembling global maps of cellular function through integrative analysis of
      physical and genetic networks.
AB  - To take full advantage of high-throughput genetic and physical interaction
      mapping projects, the raw interactions must first be assembled into models of
      cell structure and function. PanGIA (for physical and genetic interaction
      alignment) is a plug-in for the bioinformatics platform Cytoscape, designed to
      integrate physical and genetic interactions into hierarchical module maps. PanGIA
      identifies 'modules' as sets of proteins whose physical and genetic interaction
      data matches that of known protein complexes. Higher-order functional
      cooperativity and redundancy is identified by enrichment for genetic interactions
      across modules. This protocol begins with importing interaction networks into
      Cytoscape, followed by filtering and basic network visualization. Next, PanGIA is
      used to infer a set of modules and their functional inter-relationships. This
      module map is visualized in a number of intuitive ways, and modules are tested
      for functional enrichment and overlap with known complexes. The full protocol can
      be completed between 10 and 30 min, depending on the size of the data set being
      analyzed.

PMID- 21886099
TI  - Investigating protein-protein interactions in living cells using fluorescence
      lifetime imaging microscopy.
AB  - Fluorescence lifetime imaging microscopy (FLIM) is now routinely used for dynamic
      measurements of signaling events inside living cells, including detection of
      protein-protein interactions. An understanding of the basic physics of
      fluorescence lifetime measurements is required to use this technique. In this
      protocol, we describe both the time-correlated single photon counting and the
      frequency-domain methods for FLIM data acquisition and analysis. We describe
      calibration of both FLIM systems, and demonstrate how they are used to measure
      the quenched donor fluorescence lifetime that results from Forster resonance
      energy transfer (FRET). We then show how the FLIM-FRET methods are used to detect
      the dimerization of the transcription factor CCAAT/enhancer binding protein-alpha
      in live mouse pituitary cell nuclei. Notably, the factors required for accurate
      determination and reproducibility of lifetime measurements are described. With
      either method, the entire protocol including specimen preparation, imaging and
      data analysis takes ~2 d.

PMID- 21886101
TI  - In vivo optical molecular imaging and analysis in mice using dorsal window
      chamber models applied to hypoxia, vasculature and fluorescent reporters.
AB  - Optical techniques for functional imaging in mice have a number of key advantages
      over other common imaging modalities such as magnetic resonance imaging, positron
      emission tomography or computed tomography, including high resolution, low cost
      and an extensive library of available contrast agents and reporter genes. A major
      challenge to such work is the limited penetration depth imposed by tissue
      turbidity. We describe a window chamber technique by which these limitations can
      be avoided. This facilitates the study of a wide range of processes, with
      potential endpoints including longitudinal gene expression, vascular remodeling
      and angiogenesis, and tumor growth and invasion. We further describe several
      quantitative imaging and analysis techniques for characterizing in vivo
      fluorescence properties and functional endpoints, including vascular morphology
      and oxygenation. The procedure takes ~2 h to complete, plus up to several weeks
      for tumor growth and treatment procedures.

PMID- 21886100
TI  - Predicting protein-protein interactions on a proteome scale by matching
      evolutionary and structural similarities at interfaces using PRISM.
AB  - Prediction of protein-protein interactions at the structural level on the
      proteome scale is important because it allows prediction of protein function,
      helps drug discovery and takes steps toward genome-wide structural systems
      biology. We provide a protocol (termed PRISM, protein interactions by structural
      matching) for large-scale prediction of protein-protein interactions and assembly
      of protein complex structures. The method consists of two components: rigid-body
      structural comparisons of target proteins to known template protein-protein
      interfaces and flexible refinement using a docking energy function. The PRISM
      rationale follows our observation that globally different protein structures can
      interact via similar architectural motifs. PRISM predicts binding residues by
      using structural similarity and evolutionary conservation of putative binding
      residue 'hot spots'. Ultimately, PRISM could help to construct cellular pathways
      and functional, proteome-scale annotation. PRISM is implemented in Python and
      runs in a UNIX environment. The program accepts Protein Data Bank-formatted
      protein structures and is available at
      http://prism.ccbb.ku.edu.tr/prism_protocol/.

PMID- 21886102
TI  - Titration-free 454 sequencing using Y adapters.
AB  - We describe a protocol for construction and quantification of libraries for
      emulsion PCR (emPCR)-based sequencing platforms such as Roche 454 or Ion Torrent
      PGM. The protocol involves library construction using customized Y adapters,
      quantification using TaqMan-MGB (minor groove binder) probe-based quantitative
      PCR (qPCR) and calculation of an optimal template-to-bead ratio based on Poisson
      statistics, thereby avoiding the need for a laborious titration assay. Unlike
      other qPCR methods, the TaqMan-MGB probe specifically quantifies effective
      libraries in molar concentration and does not require specialized equipment. A
      single quality control step prior to emulsion PCR ensures that libraries contain
      no adapter dimers and have an optimal length distribution. The presented protocol
      takes ~7 h to prepare eight barcoded libraries from genomic DNA into libraries
      that are ready to use for full-scale emPCR. It will be useful, for example, to
      allow analyses of precious clinical samples and amplification-free
      metatranscriptomics.

PMID- 21886103
TI  - Comparative analysis of S-fatty acylation of gel-separated proteins by stable
      isotope-coded fatty acid transmethylation and mass spectrometry.
AB  - Covalent attachment of palmitic acid or other fatty acids to the thiol groups of
      cysteine residues of proteins through reversible thioester bonds has an important
      role in the regulation of diverse biological processes. We describe here the
      development of a mass spectrometry protocol based on stable isotope-coded fatty
      acid transmethylation (iFAT) for qualitative and comparative analysis of protein
      S-fatty acylation under different experimental conditions. In this approach,
      cellular proteins extracted from different cell states are separated by SDS-PAGE
      and then the gel is stained with either Coomassie blue or Nile red for improved
      sensitivity. Protein bands are excised and then an in-gel stable iFAT procedure
      is performed. The fatty acid methyl esters resulting from derivatization with d0-
      and d3-methanol are identified by mass spectrometry. By measuring the intensities
      of labeled and unlabeled fragment ion pairs of fatty acid methyl esters, the
      levels of S-fatty acylation in different cells or tissues can be compared. This
      approach has been applied to monitor the changes of S-fatty acylation of
      zebrafish liver proteome in response to environmental
      dichlorodiphenyltrichloroethane exposure. Compared with the approach using
      metabolic incorporation of radioactive fatty acid analogs, it is not only simple
      and effective but also eliminates the hazards of handling radioactive isotopes.

PMID- 21886104
TI  - High-throughput, detailed, cell-specific neuroanatomy of dendritic spines using
      microinjection and confocal microscopy.
AB  - Morphological features such as size, shape and density of dendritic spines have
      been shown to reflect important synaptic functional attributes and potential for
      plasticity. Here we describe in detail a protocol for obtaining detailed
      morphometric analysis of spines using microinjection of fluorescent dyes, high
      resolution confocal microscopy, deconvolution and image analysis with
      NeuronStudio. Recent technical advancements include better preservation of
      tissue, resulting in prolonged ability to microinject, and algorithmic
      improvements that compensate for the residual z-smear inherent in all optical
      imaging. Confocal imaging parameters were probed systematically to identify both
      optimal resolution and the highest efficiency. When combined, our methods yield
      size and density measurements comparable to serial section transmission electron
      microscopy in a fraction of the time. An experiment containing three experimental
      groups with eight subjects each can take as little as 1 month if optimized for
      speed, or approximately 4-5 months if the highest resolution and morphometric
      detail is sought.

PMID- 21886105
TI  - FLP/FRT-mediated conditional mutagenesis in pre-erythrocytic stages of Plasmodium
      berghei.
AB  - We describe here a highly efficient procedure for conditional mutagenesis in
      Plasmodium. The procedure uses the site-specific recombination FLP-FRT system of
      yeast and targets the pre-erythrocytic stages of the rodent Plasmodium parasite
      P. berghei, including the sporozoite stage and the subsequent liver stage. The
      technique consists of replacing the gene under study by an FRTed copy (i.e.,
      flanked by FRT sites) in the erythrocytic stages of a parasite clone that
      expresses the flip (FLP) recombinase stage-specifically--called the 'deleter'
      clone. We present the available deleter clones, which express FLP at different
      times of the parasite life cycle, as well as the schemes and tools for
      constructing new deleter parasites. We also outline and discuss the various
      strategies for exchanging a wild-type gene with an FRTed copy and for generating
      conditional gene knockout or knockdown parasite clones. Finally, we detail the
      protocol for obtaining sporozoites that lack a protein of interest and for
      monitoring sporozoite-specific DNA excision and depletion of the target protein.
      The protocol should allow the functional analysis of any essential protein in the
      sporozoite, liver stage or hepatic merozoite stages of rodent Plasmodium
      parasites.

PMID- 21886106
TI  - Systematic prediction of gene function in Arabidopsis thaliana using a
      probabilistic functional gene network.
AB  - AraNet is a functional gene network for the reference plant Arabidopsis and has
      been constructed in order to identify new genes associated with plant traits. It
      is highly predictive for diverse biological pathways and can be used to
      prioritize genes for functional screens. Moreover, AraNet provides a web-based
      tool with which plant biologists can efficiently discover novel functions of
      Arabidopsis genes (http://www.functionalnet.org/aranet/). This protocol explains
      how to conduct network-based prediction of gene functions using AraNet and how to
      interpret the prediction results. Functional discovery in plant biology is
      facilitated by combining candidate prioritization by AraNet with focused
      experimental tests.

PMID- 21886107
TI  - Single-molecule recognition force spectroscopy of transmembrane transporters on
      living cells.
AB  - Atomic force microscopy (AFM) has proven to be a powerful tool in biological
      sciences. Its particular advantage over other high-resolution methods commonly
      used is that biomolecules can be investigated not only under physiological
      conditions but also while they perform their biological functions. Single
      molecule force spectroscopy with AFM tip-modification techniques can provide
      insight into intermolecular forces between individual ligand-receptor pairs of
      biological systems. Here we present protocols for force spectroscopy of living
      cells, including cell sample preparation, tip chemistry, step-by-step AFM
      imaging, force spectroscopy and data analysis. We also delineate critical steps
      and describe limitations that we have experienced. The entire protocol can be
      completed in 12 h. The model studies discussed here demonstrate the power of AFM
      for studying transmembrane transporters at the single-molecule level.

PMID- 21886108
TI  - Ultrasonic neuromodulation by brain stimulation with transcranial ultrasound.
AB  - Brain stimulation methods are indispensable to the study of brain function. They
      have also proven effective for treating some neurological disorders. Historically
      used for medical imaging, ultrasound (US) has recently been shown to be capable
      of noninvasively stimulating brain activity. Here we provide a general protocol
      for the stimulation of intact mouse brain circuits using transcranial US, and,
      using a traditional mouse model of epilepsy, we describe how to use transcranial
      US to disrupt electrographic seizure activity. The advantages of US for brain
      stimulation are that it does not necessitate surgery or genetic alteration, but
      it confers spatial resolutions superior to other noninvasive methods such as
      transcranial magnetic stimulation. With a basic working knowledge of
      electrophysiology, and after an initial setup, ultrasonic neuromodulation (UNMOD)
      can be implemented in less than 1 h. Using the general protocol that we describe,
      UNMOD can be readily adapted to support a broad range of studies on brain circuit
      function and dysfunction.

PMID- 21886110
TI  - Are we jumping too early with locomotor training programs?

PMID- 21886109
TI  - Confocal laser endomicroscopy and narrow-band imaging-aided endoscopy for in vivo
      imaging of colitis and colon cancer in mice.
AB  - New endoscopic techniques such as narrow-band imaging (NBI) and confocal laser
      endomicroscopy (CLE) have improved the in vivo diagnosis of human
      gastrointestinal diseases in the colon. Whereas NBI may facilitate the
      identification of neoplastic lesions, CLE permits real-time histology of the
      inflamed or neoplastic colonic mucosa through the use of fluorescent dyes. These
      techniques have been recently adopted for use during ongoing endoscopy in mice.
      This protocol, which can be completed in 2 h, provides a detailed description of
      NBI and CLE in the mouse colon. In contrast to other techniques, this approach
      does not require laparotomy, and it allows direct CLE analysis of lesions
      identified by NBI. Mice exposed to models of colitis or colorectal cancer are
      anesthetized and examined with a miniaturized NBI endoscope, which provides an
      increased contrast of the vasculature. Upon identification of suspicious areas by
      NBI and the administration of fluorescent dyes, a confocal laser probe can be
      directed to the area of interest through the endoscope and confocal images can be
      obtained. Through the use of various fluorescent dyes, different aspects of the
      mucosa can be assessed. In addition, fluorescence-labeled antibodies can be used
      for molecular imaging of mice in vivo. Mouse NBI endoscopy and CLE represent
      reliable and fast high-quality techniques for the endoscopic characterization and
      molecular imaging of the mucosa in colitis and colon cancer.

PMID- 21886111
TI  - And then there were two.

PMID- 21886114
TI  - Gesicles: Microvesicle "cookies" for transient information transfer between
      cells.

PMID- 21886115
TI  - A GPS for heart progenitor cell lineages.

PMID- 21886116
TI  - Making sense of viral RNA sensing.

PMID- 21886119
TI  - Reality check.

PMID- 21886120
TI  - The permanent revolution.

PMID- 21886121
TI  - The Arab Spring offers hope but no quick fix.

PMID- 21886132
TI  - Japan's new leader faces energy gap.

PMID- 21886133
TI  - Halfway point for 1,001 genomes quest.

PMID- 21886134
TI  - Isotope factory accelerates.

PMID- 21886135
TI  - Twins to probe Moon's heart.

PMID- 21886136
TI  - Red tape puts chill on Siberian research.

PMID- 21886137
TI  - Scientists promised 'one voice' in European policy.

PMID- 21886138
TI  - Work ethic: The 24/7 lab.

PMID- 21886139
TI  - Neuroscience vs philosophy: Taking aim at free will.

PMID- 21886140
TI  - 24/7 isn't the only way: A healthy work-life balance can enhance research.

PMID- 21886145
TI  - Research community: Diploma database to encourage mobility.

PMID- 21886146
TI  - Pollution: Drug firm monitors waste water.

PMID- 21886147
TI  - Carbon emissions: Loophole in forest plan for Indonesia.

PMID- 21886148
TI  - Government cuts: Call to save science institute in Turkey.

PMID- 21886149
TI  - Baruj Benacerraf (1920-2011).

PMID- 21886150
TI  - HIV: How to escape treatment.

PMID- 21886151
TI  - Astrophysics: A hint of normality at last?

PMID- 21886152
TI  - Ecology: Nitrogen from the deep.

PMID- 21886153
TI  - Cancer: Tumour-fighting virus homes in.

PMID- 21886154
TI  - Ageing: Blood ties.

PMID- 21886155
TI  - Materials science: Dry solution to a sticky problem.

PMID- 21886156
TI  - Synthesis, assembly and applications of semiconductor nanomembranes.
AB  - Research in electronic nanomaterials, historically dominated by studies of
      nanocrystals/fullerenes and nanowires/nanotubes, now incorporates a growing focus
      on sheets with nanoscale thicknesses, referred to as nanomembranes. Such
      materials have practical appeal because their two-dimensional geometries
      facilitate integration into devices, with realistic pathways to manufacturing.
      Recent advances in synthesis provide access to nanomembranes with extraordinary
      properties in a variety of configurations, some of which exploit quantum and
      other size-dependent effects. This progress, together with emerging methods for
      deterministic assembly, leads to compelling opportunities for research, from
      basic studies of two-dimensional physics to the development of applications of
      heterogeneous electronics.

PMID- 21886158
TI  - An extremely primitive star in the Galactic halo.
AB  - The early Universe had a chemical composition consisting of hydrogen, helium and
      traces of lithium; almost all other elements were subsequently created in stars
      and supernovae. The mass fraction of elements more massive than helium, Z, is
      known as 'metallicity'. A number of very metal-poor stars has been found, some of
      which have a low iron abundance but are rich in carbon, nitrogen and oxygen. For
      theoretical reasons and because of an observed absence of stars with Z < 1.5 *
      10(-5), it has been suggested that low-mass stars cannot form from the primitive
      interstellar medium until it has been enriched above a critical value of Z,
      estimated to lie in the range 1.5 * 10(-8) to 1.5 * 10(-6) (ref. 8), although
      competing theories claiming the contrary do exist. (We use 'low-mass' here to
      mean a stellar mass of less than 0.8 solar masses, the stars that survive to the
      present day.) Here we report the chemical composition of a star in the Galactic
      halo with a very low Z (<= 6.9 * 10(-7), which is 4.5 * 10(-5) times that of the
      Sun) and a chemical pattern typical of classical extremely metal-poor stars--that
      is, without enrichment of carbon, nitrogen and oxygen. This shows that low-mass
      stars can be formed at very low metallicity, that is, below the critical value of
      Z. Lithium is not detected, suggesting a low-metallicity extension of the
      previously observed trend in lithium depletion. Such lithium depletion implies
      that the stellar material must have experienced temperatures above two million
      kelvin in its history, given that this is necessary to destroy lithium.

PMID- 21886159
TI  - Real-time quantum feedback prepares and stabilizes photon number states.
AB  - Feedback loops are central to most classical control procedures. A controller
      compares the signal measured by a sensor (system output) with the target value or
      set-point. It then adjusts an actuator (system input) to stabilize the signal
      around the target value. Generalizing this scheme to stabilize a micro-system's
      quantum state relies on quantum feedback, which must overcome a fundamental
      difficulty: the sensor measurements cause a random back-action on the system. An
      optimal compromise uses weak measurements, providing partial information with
      minimal perturbation. The controller should include the effect of this
      perturbation in the computation of the actuator's operation, which brings the
      incrementally perturbed state closer to the target. Although some aspects of this
      scenario have been experimentally demonstrated for the control of quantum or
      classical micro-system variables, continuous feedback loop operations that
      permanently stabilize quantum systems around a target state have not yet been
      realized. Here we have implemented such a real-time stabilizing quantum feedback
      scheme following a method inspired by ref. 13. It prepares on demand photon
      number states (Fock states) of a microwave field in a superconducting cavity, and
      subsequently reverses the effects of decoherence-induced field quantum jumps. The
      sensor is a beam of atoms crossing the cavity, which repeatedly performs weak
      quantum non-demolition measurements of the photon number. The controller is
      implemented in a real-time computer commanding the actuator, which injects
      adjusted small classical fields into the cavity between measurements. The
      microwave field is a quantum oscillator usable as a quantum memory or as a
      quantum bus swapping information between atoms. Our experiment demonstrates that
      active control can generate non-classical states of this oscillator and combat
      their decoherence, and is a significant step towards the implementation of
      complex quantum information operations.

PMID- 21886160
TI  - Increased forest ecosystem carbon and nitrogen storage from nitrogen rich
      bedrock.
AB  - Nitrogen (N) limits the productivity of many ecosystems worldwide, thereby
      restricting the ability of terrestrial ecosystems to offset the effects of rising
      atmospheric CO(2) emissions naturally. Understanding input pathways of
      bioavailable N is therefore paramount for predicting carbon (C) storage on land,
      particularly in temperate and boreal forests. Paradigms of nutrient cycling and
      limitation posit that new N enters terrestrial ecosystems solely from the
      atmosphere. Here we show that bedrock comprises a hitherto overlooked source of
      ecologically available N to forests. We report that the N content of soils and
      forest foliage on N-rich metasedimentary rocks (350-950 mg N kg(-1)) is elevated
      by more than 50% compared with similar temperate forest sites underlain by N-poor
      igneous parent material (30-70 mg N kg(-1)). Natural abundance N isotopes
      attribute this difference to rock-derived N: (15)N/(14)N values for rock, soils
      and plants are indistinguishable in sites underlain by N-rich lithology, in
      marked contrast to sites on N-poor substrates. Furthermore, forests associated
      with N-rich parent material contain on average 42% more carbon in above-ground
      tree biomass and 60% more carbon in the upper 30 cm of the soil than similar
      sites underlain by N-poor rocks. Our results raise the possibility that bedrock N
      input may represent an important and overlooked component of ecosystem N and C
      cycling elsewhere.

PMID- 21886157
TI  - Human metabolic individuality in biomedical and pharmaceutical research.
AB  - Genome-wide association studies (GWAS) have identified many risk loci for complex
      diseases, but effect sizes are typically small and information on the underlying
      biological processes is often lacking. Associations with metabolic traits as
      functional intermediates can overcome these problems and potentially inform
      individualized therapy. Here we report a comprehensive analysis of genotype
      dependent metabolic phenotypes using a GWAS with non-targeted metabolomics. We
      identified 37 genetic loci associated with blood metabolite concentrations, of
      which 25 show effect sizes that are unusually high for GWAS and account for 10
      60% differences in metabolite levels per allele copy. Our associations provide
      new functional insights for many disease-related associations that have been
      reported in previous studies, including those for cardiovascular and kidney
      disorders, type 2 diabetes, cancer, gout, venous thromboembolism and Crohn's
      disease. The study advances our knowledge of the genetic basis of metabolic
      individuality in humans and generates many new hypotheses for biomedical and
      pharmaceutical research.

PMID- 21886161
TI  - An earlier origin for the Acheulian.
AB  - The Acheulian is one of the first defined prehistoric techno-complexes and is
      characterized by shaped bifacial stone tools. It probably originated in Africa,
      spreading to Europe and Asia perhaps as early as ~1 million years (Myr) ago. The
      origin of the Acheulian is thought to have closely coincided with major changes
      in human brain evolution, allowing for further technological developments.
      Nonetheless, the emergence of the Acheulian remains unclear because well-dated
      sites older than 1.4 Myr ago are scarce. Here we report on the lithic assemblage
      and geological context for the Kokiselei 4 archaeological site from the Nachukui
      formation (West Turkana, Kenya) that bears characteristic early Acheulian tools
      and pushes the first appearance datum for this stone-age technology back to 1.76
      Myr ago. Moreover, co-occurrence of Oldowan and Acheulian artefacts at the
      Kokiselei site complex indicates that the two technologies are not mutually
      exclusive time-successive components of an evolving cultural lineage, and
      suggests that the Acheulian was either imported from another location yet to be
      identified or originated from Oldowan hominins at this vicinity. In either case,
      the Acheulian did not accompany the first human dispersal from Africa despite
      being available at the time. This may indicate that multiple groups of hominins
      distinguished by separate stone-tool-making behaviours and dispersal strategies
      coexisted in Africa at 1.76 Myr ago.

PMID- 21886166
TI  - Letter to the editor regarding 'Roh MH, Lassin Y, Miron A et al. High-grade
      fimbrial-ovarian carcinomas are unified by p53, PTEN and PAX2 expression'.

PMID- 21886163
TI  - Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in
      humans.
AB  - The efficacy and safety of biological molecules in cancer therapy, such as
      peptides and small interfering RNAs (siRNAs), could be markedly increased if high
      concentrations could be achieved and amplified selectively in tumour tissues
      versus normal tissues after intravenous administration. This has not been
      achievable so far in humans. We hypothesized that a poxvirus, which evolved for
      blood-borne systemic spread in mammals, could be engineered for cancer-selective
      replication and used as a vehicle for the intravenous delivery and expression of
      transgenes in tumours. JX-594 is an oncolytic poxvirus engineered for
      replication, transgene expression and amplification in cancer cells harbouring
      activation of the epidermal growth factor receptor (EGFR)/Ras pathway, followed
      by cell lysis and anticancer immunity. Here we show in a clinical trial that JX
      594 selectively infects, replicates and expresses transgene products in cancer
      tissue after intravenous infusion, in a dose-related fashion. Normal tissues were
      not affected clinically. This platform technology opens up the possibility of
      multifunctional products that selectively express high concentrations of several
      complementary therapeutic and imaging molecules in metastatic solid tumours in
      humans.

PMID- 21886169
TI  - Action of novel CD37 antibodies on chronic lymphocytic leukemia cells.

PMID- 21886162
TI  - The ageing systemic milieu negatively regulates neurogenesis and cognitive
      function.
AB  - In the central nervous system, ageing results in a precipitous decline in adult
      neural stem/progenitor cells and neurogenesis, with concomitant impairments in
      cognitive functions. Interestingly, such impairments can be ameliorated through
      systemic perturbations such as exercise. Here, using heterochronic parabiosis we
      show that blood-borne factors present in the systemic milieu can inhibit or
      promote adult neurogenesis in an age-dependent fashion in mice. Accordingly,
      exposing a young mouse to an old systemic environment or to plasma from old mice
      decreased synaptic plasticity, and impaired contextual fear conditioning and
      spatial learning and memory. We identify chemokines--including CCL11 (also known
      as eotaxin)--the plasma levels of which correlate with reduced neurogenesis in
      heterochronic parabionts and aged mice, and the levels of which are increased in
      the plasma and cerebrospinal fluid of healthy ageing humans. Lastly, increasing
      peripheral CCL11 chemokine levels in vivo in young mice decreased adult
      neurogenesis and impaired learning and memory. Together our data indicate that
      the decline in neurogenesis and cognitive impairments observed during ageing can
      be in part attributed to changes in blood-borne factors.

PMID- 21886170
TI  - The vascular niche: home for normal and malignant hematopoietic stem cells.
AB  - Hematopoietic stem cells (HSCs) are uniquely capable of self-renewal and
      provision of all of the mature elements of the blood and immune system throughout
      the lifetime of an individual. HSC self-renewal is regulated by both intrinsic
      mechanisms and extrinsic signals mediated via specialized microenvironments or
      'niches' wherein HSCs reside. HSCs have been shown to reside in close association
      with bone marrow (BM) osteoblasts in the endosteal niche and also in proximity to
      BM sinusoidal vessels. An unresolved question surrounds whether the endosteal and
      vascular niches provide synchronous or redundant regulation of HSC fate or
      whether these niches provide wholly unique regulatory functions. Furthermore,
      while some aspects of the mechanisms through which osteoblasts regulate HSC fate
      have been defined, the mechanisms through which the vascular niche regulates HSC
      fate remain obscure. Here, we summarize the anatomic and functional basis
      supporting the concept of an HSC vascular niche as well as the precise function
      of endothelial cells, perivascular cells and stromal cells within the niche in
      regulating HSC fate. Lastly, we will highlight the role of the vascular niche in
      regulating leukemic stem cell fate in vivo.

PMID- 21886171
TI  - Azacitidine for treatment of imminent relapse in MDS or AML patients after
      allogeneic HSCT: results of the RELAZA trial.
AB  - This study evaluated azacitidine as treatment of minimal residual disease (MRD)
      determined by a sensitive donor chimerism analysis of CD34(+) blood cells to pre
      empt relapse in patients with CD34(+) myelodysplastic syndromes (MDS) or acute
      myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation
      (HSCT). At a median of 169 days after HSCT, 20/59 prospectively screened patients
      experienced a decrease of CD34(+) donor chimerism to <80% and received four
      azacitidine cycles (75 mg/m(2)/day for 7 days) while in complete hematologic
      remission. A total of 16 patients (80%) responded with either increasing CD34(+)
      donor chimerism to >=80% (n=10; 50%) or stabilization (n=6; 30%) in the absence
      of relapse. Stabilized patients and those with a later drop of CD34(+) donor
      chimerism to <80% after initial response were eligible for subsequent azacitidine
      cycles. A total of 11 patients (55%) received a median of 4 (range, 1-11)
      additional cycles. Eventually, hematologic relapse occurred in 13 patients (65%),
      but was delayed until a median of 231 days (range, 56-558) after initial decrease
      of CD34(+) donor chimerism to <80%. In conclusion, pre-emptive azacitidine
      treatment has an acceptable safety profile and can substantially prevent or delay
      hematologic relapse in patients with MDS or AML and MRD after allogeneic HSCT.

PMID- 21886172
TI  - Release of intracellular calcium primes chronic myeloid leukaemia cells for
      tyrosine kinase inhibitor-induced apoptosis.
AB  - Imatinib is a substrate for hOCT1 (SLC22A1) and inhibitors of this influx
      transporter, such as amantadine and prazosin, have previously been shown to
      decrease cellular imatinib uptake. However, here we report that in longer term
      experiments, both drugs paradoxically increase the cytotoxicity of all three
      currently licensed tyrosine kinase inhibitors (TKIs), imatinib, nilotinib and
      dasatinib. This effect is due to release of intracellular calcium from the
      endoplasmic reticulum (ER), with changes in mitochondrial calcium and alterations
      in mitochondrial membrane permeability, resulting in caspase-mediated apoptosis.
      The effect is confined to BCR-ABL-positive cells, and is greater in primary cells
      than in cell lines. Furthermore, in primary cells at original diagnosis, the
      effect is only seen in samples from patients destined to become complete
      cytogenetic responders to imatinib. These results indicate that calcium release
      from the ER, here induced by amantadine or prazosin, may prime BCR-ABL-positive
      cells to TKI-induced apoptosis. Amantadine/prazosin primed TKI cytotoxicity in
      vitro may be a useful test for the level of ER-releasable calcium, and may be of
      prognostic value.

PMID- 21886174
TI  - SF3B1, a splicing factor is frequently mutated in refractory anemia with ring
      sideroblasts.

PMID- 21886173
TI  - Mobilization of hematopoietic stem and progenitor cells using inhibitors of CXCR4
      and VLA-4.
AB  - Successful hematopoietic stem cell transplant requires the infusion of a
      sufficient number of hematopoietic stem/progenitor cells (HSPCs) that are capable
      of homing to the bone marrow cavity and regenerating durable trilineage
      hematopoiesis in a timely manner. Stem cells harvested from peripheral blood are
      the most commonly used graft source in HSCT. Although granulocyte colony
      stimulating factor (G-CSF) is the most frequently used agent for stem cell
      mobilization, the use of G-CSF alone results in suboptimal stem cell yields in a
      significant proportion of patients. Both the chemokine receptor CXCR4 and the
      integrin alpha(4)beta(1) (very late antigen 4 (VLA-4)) have important roles in
      the homing and retention of HSPCs within the bone marrow microenvironment.
      Preclinical and/or clinical studies have shown that targeted disruption of the
      interaction of CXCR4 or VLA-4 with their ligands results in the rapid and
      reversible mobilization of hematopoietic stem cells into the peripheral
      circulation and is synergistic when combined with G-CSF. In this review, we
      discuss the development of small-molecule CXCR4 and VLA-4 inhibitors and how they
      may improve the utility and convenience of peripheral blood stem cell
      transplantation.

PMID- 21886177
TI  - A new Canterbury tale: the eighth International Meeting on Yeast Apoptosis in
      Canterbury, UK, 2-6 May 2011.

PMID- 21886175
TI  - A novel perspective on stem cell homing and mobilization: review on bioactive
      lipids as potent chemoattractants and cationic peptides as underappreciated
      modulators of responsiveness to SDF-1 gradients.
AB  - Hematopoietic stem progenitor cells (HSPCs) respond robustly to alpha-chemokine
      stromal-derived factor-1 (SDF-1) gradients, and blockage of CXCR4, a seven
      transmembrane-spanning G(alphaI)-protein-coupled SDF-1 receptor, mobilizes HSPCs
      into peripheral blood. Although the SDF-1-CXCR4 axis has an unquestionably
      important role in the retention of HSPCs in bone marrow (BM), new evidence shows
      that, in addition to SDF-1, the migration of HSPCs is directed by gradients of
      the bioactive lipids sphingosine-1 phosphate and ceramide-1 phosphate.
      Furthermore, the SDF-1 gradient may be positively primed/modulated by cationic
      peptides (C3a anaphylatoxin and cathelicidin) and, as previously demonstrated,
      HSPCs respond robustly even to very low SDF-1 gradients in the presence of
      priming factors. In this review, we discuss the role of bioactive lipids in stem
      cell trafficking and the consequences of HSPC priming by cationic peptides.
      Together, these phenomena support a picture in which the SDF-1-CXCR4 axis
      modulates homing, BM retention and mobilization of HSPCs in a more complex way
      than previously envisioned.

PMID- 21886178
TI  - Drosophila BRUCE inhibits apoptosis through non-lysine ubiquitination of the IAP
      antagonist REAPER.
AB  - Active caspases execute apoptosis to eliminate superfluous or harmful cells in
      animals. In Drosophila, living cells prevent uncontrolled caspase activation
      through an inhibitor of apoptosis protein (IAP) family member, dIAP1, and
      apoptosis is preceded by the expression of IAP-antagonists, such as Reaper, Hid
      and Grim. Strong genetic modifiers of this pathway include another IAP family
      gene encoding an E2 ubiquitin conjugating enzyme domain, dBruce. Although the
      genetic effects of dBruce mutants are well documented, molecular targets of its
      encoded protein have remained elusive. Here, we report that dBruce targets Reaper
      for ubiquitination through an unconventional mechanism. Specifically, we show
      that dBruce physically interacts with Reaper, dependent upon Reaper's IAP-binding
      (IBM) and GH3 motifs. Consistently, Reaper levels were elevated in a dBruce -/-
      background. Unexpectedly, we found that dBruce also affects the levels of a
      mutant form of Reaper without any internal lysine residues, which normally serve
      as conventional ubiquitin acceptor sites. Furthermore, we were able to
      biochemically detect ubiquitin conjugation on lysine-deficient Reaper proteins,
      and knockdown of dBruce significantly reduced the extent of this ubiquitination.
      Our results indicate that dBruce inhibits apoptosis by promoting IAP-antagonist
      ubiquitination on unconventional acceptor sites.

PMID- 21886179
TI  - A dp53/JNK-dependant feedback amplification loop is essential for the apoptotic
      response to stress in Drosophila.
AB  - Programmed cell death (apoptosis) is a conserved process aimed to eliminate
      unwanted cells. The key molecules are a group of proteases called caspases that
      cleave vital proteins, which leads to the death of cells. In Drosophila, the
      apoptotic pathway is usually represented as a cascade of events in which an
      initial stimulus activates one or more of the proapoptotic genes (hid, rpr,
      grim), which in turn activate caspases. In stress-induced apoptosis, the dp53
      (Drosophila p53) gene and the Jun N-terminal kinase (JNK) pathway function
      upstream in the activation of the proapoptotic genes. Here we demonstrate that
      dp53 and JNK also function downstream of proapoptotic genes and the initiator
      caspase Dronc (Drosophila NEDD2-like caspase) and that they establish a feedback
      loop that amplifies the initial apoptotic stimulus. This loop plays a critical
      role in the apoptotic response because in its absence there is a dramatic
      decrease in the amount of cell death after a pulse of the proapoptotic proteins
      Hid and Rpr. Thus, our results indicate that stress-induced apoptosis in
      Drosophila is dependant on an amplification loop mediated by dp53 and JNK.
      Furthermore, they also demonstrate a mechanism of mutual activation of
      proapoptotic genes.

PMID- 21886180
TI  - PI3K/AKT signaling determines a dynamic switch between distinct KSRP functions
      favoring skeletal myogenesis.
AB  - Skeletal myogenesis is orchestrated by distinct regulatory signaling pathways,
      including PI3K/AKT, that ultimately control muscle gene expression. Recently
      discovered myogenic micro-RNAs (miRNAs) are deeply implicated in muscle biology.
      Processing of miRNAs from their primary transcripts is emerging as a major step
      in the control of miRNA levels and might be well suited to be regulated by
      extracellular signals. Here we report that the RNA binding protein KSRP is
      required for the correct processing of primary myogenic miRNAs upon PI3K/AKT
      activation in myoblasts C2C12 and in the course of injury-induced muscle
      regeneration, as revealed by Ksrp knock-out mice analysis. PI3K/AKT activation
      regulates in opposite ways two distinct KSRP functions inhibiting its ability to
      promote decay of myogenin mRNA and activating its ability to favor maturation of
      myogenic miRNAs. This dynamic regulatory switch eventually contributes to the
      activation of the myogenic program.

PMID- 21886181
TI  - Evidence that CED-9/Bcl2 and CED-4/Apaf-1 localization is not consistent with the
      current model for C. elegans apoptosis induction.
AB  - In C. elegans, the BH3-only domain protein EGL-1, the Apaf-1 homolog CED-4 and
      the CED-3 caspase are required for apoptosis induction, whereas the Bcl-2 homolog
      CED-9 prevents apoptosis. Mammalian B-cell lymphoma 2 (Bcl-2) inhibits apoptosis
      by preventing the release of the Apaf-1 (apoptotic protease-activating factor 1)
      activator cytochrome c from mitochondria. In contrast, C. elegans CED-9 is
      thought to inhibit CED-4 by sequestering it at the outer mitochondrial membrane
      by direct binding. We show that CED-9 associates with the outer mitochondrial
      membrane within distinct foci that do not overlap with CED-4, which is
      predominantly perinuclear and does not localize to mitochondria. CED-4 further
      accumulates in the perinuclear space in response to proapoptotic stimuli such as
      ionizing radiation. This increased accumulation depends on EGL-1 and is abrogated
      in ced-9 gain-of-function mutants. CED-4 accumulation is not sufficient to
      trigger apoptosis execution, even though it may prime cells for apoptosis. Our
      results suggest that the cell death protection conferred by CED-9 cannot be
      solely explained by a direct interaction with CED-4.

PMID- 21886182
TI  - A genome-wide RNA interference screen uncovers two p24 proteins as regulators of
      Wingless secretion.
AB  - Wnt proteins are secreted, lipid-modified glycoproteins that control animal
      development and adult tissue homeostasis. Secretion of Wnt proteins is at least
      partly regulated by a dedicated machinery. Here, we report a genome-wide RNA
      interference screen for genes involved in the secretion of Wingless (Wg), a
      Drosophila Wnt. We identify three new genes required for Wg secretion. Of these,
      Emp24 and Eclair are required for proper export of Wg from the endoplasmic
      reticulum (ER). We propose that Emp24 and Eca act as specific cargo receptors for
      Wg to concentrate it in forming vesicles at sites of ER export.

PMID- 21886184
TI  - Neurodegenerative disease: alpha-synuclein gets a new look.

PMID- 21886183
TI  - The interplay between morphogens and tissue growth.
AB  - Morphogens are conserved, secreted signalling molecules that regulate the size,
      shape and patterning of animal tissues and organs. Recent experimental evidence
      has emphasized the fundamental role of tissue growth in expanding the expression
      domains of morphogens and their target genes, in generating morphogen gradients
      and in modulating the response of cells to morphogens. Moreover, the classic view
      of how morphogens, particularly through their concentration gradient, regulate
      tissue size during development has been revisited recently. In this review, we
      discuss how morphogens and tissue growth affect each other, and we attempt to
      integrate genetic and molecular evidence from vertebrate and invertebrate model
      systems to put forward the idea that the interaction between growth and
      morphogens is a general feature of highly proliferative tissues.

PMID- 21886185
TI  - Synaptic plasticity: a key player in presynaptic plasticity.

PMID- 21886188
TI  - Telomeres: Fusing with RNF8.

PMID- 21886187
TI  - Dynamic niches in the origination and differentiation of haematopoietic stem
      cells.
AB  - Haematopoietic stem cells (HSCs) are multipotent, self-renewing progenitors that
      generate all mature blood cells. HSC function is tightly controlled to maintain
      haematopoietic homeostasis, and this regulation relies on specialized cells and
      factors that constitute the haematopoietic 'niche', or microenvironment. Recent
      discoveries, aided in part by technological advances in in vivo imaging, have
      engendered a new appreciation for the dynamic nature of the niche, identifying
      novel cellular and acellular niche components and uncovering fluctuations in the
      relative importance of these components over time. These new insights
      significantly improve our understanding of haematopoiesis and raise fundamental
      questions about what truly constitutes a stem cell niche.

PMID- 21886189
TI  - Use of systemic steroid after successful macular surgery in eyes with epiretinal
      membrane: a randomized, controlled clinical study.
AB  - PURPOSE: To evaluate the functional and morphological outcomes of postoperative
      systemic steroid therapy after successful macular surgery in eyes with macular
      edema due to idiopathic macular epiretinal membranes (ERMs). DESIGN: Prospective,
      randomized, investigator-masked, controlled clinical study. METHODS: Twenty-eight
      patients scheduled for 23-gauge vitrectomy combined with ERM and inner limiting
      membrane (ILM) peeling for macular edema due to ERM were included in this single
      center trial. Patients were randomized to receive oral steroid therapy
      (Prednisolone, 100 mg per day for 5 days) or no oral steroid (control group)
      after surgery. Main outcome measures included best corrected visual acuity (BCVA;
      Early Treatment Diabetic Retinopathy Study), central retinal thickness (CRT),
      retinal volume (RV), and macular morphology as determined by spectral domain
      optical coherence tomography (SD-OCT, Cirrus). Examinations were carried out
      preoperatively and at week 1, at months 1 and 3, postoperatively. RESULTS: At
      month 3, mean BCVA improved to a eight-letter gain in each study group (P<0.01
      compared with baseline for both groups), showing no statistically significant
      difference between both the groups (P=0.19). Morphologically, retinal surface
      folds resolved within 1 month after surgery in both treatment groups, followed by
      a progressive recovery of retinal layer integrity and a statistical significant
      (P<0.01) decrease in CRT and RV without significant differences between both
      groups (P=0.62, P=0.13, respectively, ANOVA between the groups). CONCLUSION: The
      early postoperative use of systemic steroid treatment after successful vitrectomy
      combined with ERM and ILM peeling does not seem to improve significantly the
      anatomic and functional outcomes in eyes with ERM.

PMID- 21886190
TI  - Mining the adenovirus virome for oncolytics against multiple solid tumor types.
AB  - Although there are 55 serotypes of adenovirus (Ad) that infect humans, Ad
      serotype 5 (Ad5) is the most widely studied because of the availability of
      commercial kits for its genetic manipulation. In fact, engineered Ad 5 is
      currently being used in all of the 87 global clinical trials utilizing Ad for the
      treatment of cancer. Unfortunately, Ad5 is one of the most seroprevalent
      serotypes, meaning that this virus has to confront additional immunological
      barriers to be effective in Ad5-immune patients. In this work, we compare Ad5 to
      13 other adenoviral serotypes from species B, C, D and E for oncolytic potential
      in both immunodeficient mouse and immunocompetent hamster models. Our results
      indicate that species D Ads are not effective oncolytics against most solid
      tumors. Conversely, lower seroprevalent Ad6 and Ad11 had anti-cancer activity
      comparable to Ad5. This work strongly supports the consideration of Ad6-based
      oncolytic therapies for the treatment of breast, ovarian, kidney and liver
      tumors.

PMID- 21886186
TI  - Linking neural activity and molecular oscillations in the SCN.
AB  - Neurons in the suprachiasmatic nucleus (SCN) function as part of a central timing
      circuit that drives daily changes in our behaviour and underlying physiology. A
      hallmark feature of SCN neuronal populations is that they are mostly electrically
      silent during the night, start to fire action potentials near dawn and then
      continue to generate action potentials with a slow and steady pace all day long.
      Sets of currents are responsible for this daily rhythm, with the strongest
      evidence for persistent Na(+) currents, L-type Ca(2+) currents, hyperpolarization
      activated currents (I(H)), large-conductance Ca(2+) activated K(+) (BK) currents
      and fast delayed rectifier (FDR) K(+) currents. These rhythms in electrical
      activity are crucial for the function of the circadian timing system, including
      the expression of clock genes, and decline with ageing and disease. This article
      reviews our current understanding of the ionic and molecular mechanisms that
      drive the rhythmic firing patterns in the SCN.

PMID- 21886193
TI  - Self-referenced method for terahertz wave time-domain spectroscopy.
AB  - The method allows retrieval of the absorbance of a sample without the need for a
      reference measurement. The method measures the dynamic variation of frequency
      resolution as the waveform is being acquired. In terahertz wave time-domain
      spectroscopy, the frequency resolution increases as the temporal window
      increases. Therefore, narrow absorption peaks will appear in the spectrum when
      the temporal window is long enough to resolve the peak. By measuring the dynamic
      values of each frequency component at specific points in time, a reference value
      and a peak value are extracted and, hence, the self-referenced is achieved. In
      addition, the method provides a mechanism to remove the effects of echoes, which
      enables arbitrary temporal window length and, thus, achieves high-resolution
      frequency. Examples of extraction of the water vapor lines and resonant features
      in gas and semiconductors are demonstrated in transmission and reflection
      geometries.

PMID- 21886191
TI  - Vesicular stomatitis virus as a treatment for colorectal cancer.
AB  - M protein mutant vesicular stomatitis virus is an attractive candidate oncolytic
      virus for the treatment of metastatic colorectal cancer due to its ability to
      kill cancer cells that are defective in their antiviral responses. The oncolytic
      activity of recombinant wild-type and M protein mutant vesicular stomatitis
      viruses was determined in RKO, Hct116 and LoVo colorectal cancer cells, as well
      as in human fibroblast and hepatocyte primary cultures. RKO and Hct116 cells were
      sensitive to both viruses, whereas LoVo cells were resistant. [(35)S]methionine
      labeling experiments and viral plaque assays showed that sensitive and resistant
      colorectal cancer cells supported viral protein and progeny production after
      infection with either virus. Colorectal cancer cells were pretreated with beta
      interferon and infected with vesicular stomatitis virus to evaluate the extent to
      which interferon signaling is downregulated in colorectal cancer cells. Although
      colorectal cancer cells retained some degree of interferon signaling, this
      signaling did not negatively impact the oncolytic effects of either virus in
      sensitive cells. Murine xenografts of RKO cells were effectively treated by
      intratumoral injections with M protein mutant virus, whereas LoVo xenografts were
      resistant to treatment with this virus. These results suggest that M protein
      mutant vesicular stomatitis virus is a good candidate oncolytic virus for the
      treatment of selected metastatic colorectal cancers.

PMID- 21886192
TI  - Maskless laser tailoring of conical pillar arrays for antireflective biomimetic
      surfaces.
AB  - Herein, we report a facile approach for rapid and maskless production of
      subwavelength structured antireflective surfaces with high and broadband
      transmittance-direct laser interference ablation. The interfered laser beams were
      introduced into the surface of a bare optical substrate, where structured
      surfaces consisting of a micropillar array were produced by two-step laser
      irradiation in the time frame of seconds. A multiple exposure of the two-beam
      interference approach was proposed instead of multiple-beam interference to
      simply realize planar patterns of a high aspect ratio. Tall sinusoidal pillars
      were created and shaped by pulse shot number control. As an example of the
      application, zinc sulfide substrates were processed with the technology, from
      which high transmission at an infrared wavelength, over 92%, at normal incidence
      was experimentally achieved.

PMID- 21886194
TI  - Methods and evaluation of frequency aging in distributed-feedback laser diodes
      for rubidium atomic clocks.
AB  - Distributed-feedback laser diodes emitting at 780 nm have been evaluated, with
      respect to the aging of the injection current required for reaching the rubidium
      D2 resonance line. Results obtained for lasers operating in air and in vacuum for
      9 months are reported. When operated at constant temperature, the laser current
      required for emission at the wavelength of the desired atomic resonance is found
      to decrease by 50 to 80 MUA per month. The impact of this result on the lifetime
      and long-term performances of laser-pumped rubidium atomic clocks is discussed.

PMID- 21886195
TI  - Demonstration of a directed optical decoder using two cascaded microring
      resonators.
AB  - We propose and demonstrate a directed optical decoder that can perform the
      decoding function from a two-bit electrical signal to a four-bit optical signal
      based on two cascaded microring resonators. We use two electrical signals
      regarded as a two-bit electrical signal to modulate the two microring resonators
      through the thermo-optic effect and four optical signals regarded as a four-bit
      optical signal appear at the output ports, respectively. The device operating at
      10 kbps is demonstrated.

PMID- 21886196
TI  - Deciphering fluorescence signals by quantifying separately the excitation
      intensity from the number of emitters.
AB  - Conventional fluorescence detection is sensitive to an intricate product of the
      number of fluorescent emitters times the local excitation intensity. Here, we
      describe a method to locally quantify the excitation intensity and the number of
      emitters separately, enabling a clear distinction between the phenomena
      responsible for a given fluorescence signal. Our technique is based on harmonic
      excitation modulation and higher-order fluorescence demodulation. It is
      compatible with a wide range of observations, opening new characterization routes
      for fluorescence detection or imaging on complex systems, such as plasmonic
      substrates or scattering media.

PMID- 21886197
TI  - Vernier-cascade label-free biosensor with integrated arrayed waveguide grating
      for wavelength interrogation with low-cost broadband source.
AB  - Recently, cheap silicon-on-insulator label-free biosensors have been demonstrated
      that allow fast and accurate quantitative detection of biologically relevant
      molecules for applications in medical diagnostics and drug development. However,
      whereas the sensor chip can be made cheaply, an expensive tunable laser is
      typically required to accurately monitor spectral shifts in the sensor's
      transmission spectrum (wavelength interrogation). To address this issue, we
      integrated a very sensitive Vernier-cascade sensor with an arrayed waveguide
      grating spectral filter that divides the sensor's transmission spectrum in
      multiple wavelength channels and transmits them to spatially separated output
      ports, allowing wavelength interrogation with a much cheaper broadband light
      source. Experiments show that this sensor can monitor refractive index changes of
      watery solutions in real time with a detection limit (1.6.10(-5) RIU) competitive
      with more expensive interrogation schemes, indicating its applicability in low
      cost label-free biosensing. The relaxation on the complexity of the source,
      moreover, offers the prospect to integrate the source and detectors to further
      reduce the device cost and to increase its portability.

PMID- 21886198
TI  - Spectral contrast imaging microscopy.
AB  - We introduce a new technique, spectral contrast imaging microscopy (SCIM), for
      super-resolution microscopic imaging. Based on a novel contrast mechanism that
      encodes each local spatial frequency with a corresponding optical wavelength,
      SCIM provides a real-time high-resolution spectral contrast microscopic image
      with superior contrast. We show that two microscopic objects, separated by a
      distance smaller than the diffraction limit of the optical system, can be
      spatially resolved in the SCIM image as different colors. Results with numerical
      simulation and experiments using a high-resolution United States Air Force target
      are presented. The ability of SCIM for imaging biological cells is also
      demonstrated.

PMID- 21886199
TI  - Dielectric supported ring-shaped metal disks on a metal film for ultrasensitive
      refractive index sensing.
AB  - We experimentally report a magnetic plasmonic metamaterial, which is constructed
      with a metal ring-shaped disk array supported by a dielectric layer on a metal
      film for high sensitive refractive index sensing. An ultrasensitive refractive
      index sensitivity of about 1842 nm per refractive index unit is achieved through
      the reflection spectrum measurement. We attribute the high sensitivity to greatly
      enhanced electric field intensity and its large spatial overlapping with the
      surrounding medium to sense. The present plasmonic structure provides an
      effective way for high sensitive chip-based biochemical sensors and integrated
      devices.

PMID- 21886200
TI  - Method for vector characterization of polar liquids using frequency-domain
      spectroscopy.
AB  - A device for performing vector transmission spectroscopy on aqueous and polar
      solvent specimens at terahertz frequencies is presented. The device enables the
      direct measurement of the complex dielectric function across the terahertz band
      using a Fourier transform IR spectrometer for lossy solutions. Using microfluidic
      sampling, specimen handling is straightforward and direct measurements on polar
      specimens are made possible. The method is scalable to longer or shorter
      wavelengths.

PMID- 21886201
TI  - Direct determination of diffusion properties of random media from speckle
      contrast.
AB  - We present a simple scheme to determine the diffusion properties of a thin slab
      of strongly scattering material by measuring the speckle contrast resulting from
      the transmission of a femtosecond pulse with controlled bandwidth. In contrast
      with previous methods, our scheme does not require time measurements nor
      interferometry. It is well adapted to the characterization of samples for pulse
      shaping, nonlinear excitation through scattering media, and biological imaging.

PMID- 21886202
TI  - Average capacity of free-space optical systems for a partially coherent beam
      propagating through non-Kolmogorov turbulence.
AB  - The performance of partially coherent free-space optical links is investigated in
      the moderate to strong fluctuation regime of non-Kolmogorov turbulence. The
      expressions for large- and small-scale log-irradiance flux variance are obtained
      in non-Kolmogorov turbulence. By employing the gamma-gamma distribution of
      irradiance fluctuations, the effects of spatial coherence of the source, index of
      non-Kolmogorov spectrum, and size of the receiver on channel capacity for
      horizontal links are discussed. Results show that channel capacity presents
      fluctuating behaviors with the variation of alpha for longer links and increases
      for alpha values higher than 11/3.

PMID- 21886203
TI  - Surface acoustic wave opto-mechanical oscillator and frequency comb generator.
AB  - We report on realization of an efficient triply resonant coupling between two
      long lived optical modes and a high frequency surface acoustic wave (SAW) mode of
      the same monolithic crystalline whispering gallery mode resonator. The coupling
      results in an opto-mechanical oscillation and generation of a monochromatic SAW.
      A strong nonlinear interaction of this mechanical mode with other equidistant SAW
      modes leads to mechanical hyperparametric oscillation and generation of a SAW
      pulse train and associated frequency comb in the resonator. We visualized the
      comb by observing the modulation of the light escaping the resonator.

PMID- 21886204
TI  - Viscoelasticity imaging of biological tissues with phase-resolved photoacoustic
      measurement.
AB  - A method for noninvasive viscoelasticity imaging of biological tissues using
      phase-resolved photoacoustic measurement is presented. We deduced the process of
      photoacoustic effect on the basis of thermal viscoelasticity theory, and
      established the relationship between the photoacoustic phase delay and the
      viscosity-elasticity ratio for soft solids. Agar phantoms with different
      densities and different absorption coefficients were used to verify the
      dependence of photoacoustic phase-resolved viscoelasticity measurements.
      Moreover, viscoelasticity imaging of tissues was obtained with a photoacoustic
      point scanning system. The photoacoustic phase-resolved method provides a basis
      for viscoelasticity imaging, which can potentially be used for detection of
      viscoelastic properties and lesions of biological tissues.

PMID- 21886205
TI  - Infrared suppression by hybrid EUV multilayer--IR etalon structures.
AB  - We have developed a multilayer mirror for extreme UV (EUV) radiation (13.5 nm),
      which has near-zero reflectance for IR line radiation (10.6 MUm). The EUV
      reflecting multilayer is based on alternating B4C and Si layers. Substantial
      transparency of these materials with respect to the IR radiation allowed the
      integration of the multilayer coating in a resonant quarter-wave structure for
      10.6 MUm. Samples were manufactured using magnetron sputtering deposition
      technique and demonstrated suppression of the IR radiation by up to 3 orders of
      magnitude. The EUV peak reflectance amounts 45% at 13.5 nm, with a bandwidth at
      FWHM being 0.284 nm. Therefore such a mirror could replace conventional
      multilayer mirrors to suppress undesired spectral components in monochromatic
      imaging applications, including EUV photolithography.

PMID- 21886206
TI  - Waveguide trapping of hollow glass spheres.
AB  - Microparticles can be trapped and propelled by the evanescent field of optical
      waveguides. As the evanescent field only stretches 100-200 nm from the surface of
      the waveguide, only the lower caps of the microparticles interact directly with
      the field. This is taken advantage of by trapping hollow glass spheres on
      waveguides in the same way as solid glass spheres. For the chosen waveguide,
      numerical simulations show that hollow microspheres with a shell thickness above
      60 nm can be stably trapped, while spheres with thinner shells are repelled. The
      average refractive index of the sphere-field intersection volume is used to
      explain the result in a qualitative way.

PMID- 21886207
TI  - Nanofiltering via integrated liquid core waveguides.
AB  - We demonstrate and describe how nanoporous liquid core waveguides can exclude
      scattering particles, making them an ideal integrated platform for analysis of
      turbid solutions. Milk with 0.5% fat showed an optical propagation loss of 0.05
      dB/mm at 633 nm in nanoporous waveguides compared to the 10.6 dB/mm loss in
      standard cuvette measurements. To examine the nanofiltering effect, waveguides
      were infiltrated with solutions containing Rhodamine B molecules (1 nm) and 22 nm
      red fluorescing polystyrene beads. With fluorescence spectroscopy we show that 22
      nm beads are excluded, while Rhodamine B molecules penetrate the waveguides. This
      is further confirmed by fluorescence microscopy, also revealing a homogenous
      distribution of Rhodamine in the waveguide volume.

PMID- 21886208
TI  - Femtosecond and nanosecond laser fabricated substrate for surface-enhanced Raman
      scattering.
AB  - We report a simple and repeatable method for fabricating a large-area substrate
      for surface-enhanced Raman scattering. The substrate was processed by three
      steps: (i) femtosecond (fs) laser micromachining and roughening, (ii) thin-film
      coating, and (iii) nanosecond laser heating and melting. Numerous gold
      nanoparticles of various sizes were created on the surface of the silicon
      substrate. The 3D micro-/nanostructures generated by the fs laser provide greater
      surface areas with more nanoparticles leading to 2 orders of magnitude higher of
      the enhancement factor than in the case of a flat substrate. Using an He-Ne laser
      with a 632.8 nm excitation wavelength, the surface-enhanced Raman scattering
      enhancement factor for Rhodamine 6G was measured up to 2*10(7).

PMID- 21886209
TI  - Quasi-monochromatic bound on ultrashort light-pulse transmission through fog.
AB  - The use of ultrashort (femtosecond duration) light pulses for line-of-sight free
      space optical (FSO) communication through fog is receiving increasing attention.
      Assuming that the transmitter power is low enough to preclude nonlinear
      interactions, and that scattering-induced multipath spread is less than the
      reciprocal of the scattering-induced Doppler spread, it is shown that the average
      transmitter-to-receiver fractional energy transfer of an ultrafast FSO system
      cannot exceed that of a quasimonochromatic (nanosecond pulse duration) system
      operating at the optimum wavelength within the ultrafast system's spectrum. Thus,
      an ultrashort-pulse system is not a solution for high-data-rate FSO communication
      through fog, because, at best, it will reproduce on average the energy-transfer
      performance of a wavelength-optimized quasimonochromatic system.

PMID- 21886210
TI  - Optical properties of a planar metamaterial with chiral symmetry breaking.
AB  - The optical properties of a planar metamaterial with gammadion-shaped chiral
      symmetry breaking holes array have been investigated both theoretically and
      experimentally. The results indicate that the introduction of the chiral symmetry
      breaking causes the split of the transmission peak and exerts large influence on
      the optical rotation and circular dichroism. Our metamaterials might have
      potential applications in future design of plasmonic devices.

PMID- 21886211
TI  - Mode-filtered large-core fiber for short-pulse delivery with reduced nonlinear
      effects.
AB  - We present a large-core fiber (LCF) with a reduced nonlinear property for a
      single-mode beam delivery of intense ultrashort pulses. A tapered-fiber mode
      filter was fabricated in an LCF with the core diameter decreased from 20 MUm to 6
      MUm at the tapered waist region surrounded by index-matched liquid. By the
      tapered geometry, the high-order mode was rejected so that our mode-filtered LCF
      acted as a single-mode fiber despite the multimode property of the original LCF.
      It has been found that this fiber class is suitable for applications, such as an
      endoscopic multiphoton microscope, that demand a flexible short-distance (<4 m)
      delivery medium of ultrashort pulses.

PMID- 21886212
TI  - Conditions for practicing compressive Fresnel holography.
AB  - Recent works have applied diffraction-based wave propagation for compressive
      imaging applications. In this Letter, we derive the theoretical bounds on the
      performance of compressive imaging systems based on Fresnel wave propagation, and
      we show that it is related to the imaging sensor's physical attributes,
      illumination wavelength, and working distance.

PMID- 21886213
TI  - Crucial role of the emitter-particle distance on the directivity of optical
      antennas.
AB  - We demonstrate that the reflecting properties of a single particle nanoantenna
      can be extremely sensitive to its distance from a quantum emitter at frequencies
      lower than the plasmon resonance. The phenomenon is shown to arise from rapid
      phase variations of the emitter field at short distances associated with a phase
      of the antenna particle polarizability lower than pi/4.

PMID- 21886214
TI  - Efficient second-harmonic generation in nonlinear plasmonic waveguide.
AB  - We theoretically studied a nonlinear optical process in a hybrid plasmonic
      waveguide composed of a nonlinear dielectric waveguide and a metal film with a
      separation of a thin air gap. Owing to the hybridization effect of guided mode
      and surface plasmon polariton mode, this particular waveguide is able to confine
      the optical-field in a deep subwavelength scale together with low propagation
      loss. Based on this, efficient second-harmonic generations (SHG) were revealed at
      the fundamental wavelength of lambda=1.55 MUm with good field confinement. The
      SHG efficiency, as well as the coupling coefficient and mode area, were analyzed
      and discussed in detail with respect to the structural parameters.

PMID- 21886215
TI  - Dispersion relation for surface plasmon polaritons in metal/nonlinear
      dielectric/metal slot waveguides.
AB  - We present the first (to our knowledge) exact dispersion relation for the
      transverse-magnetic surface plasmon polariton (SPP) modes of a plasmonic slot
      waveguide, which is formed by a nonlinear Kerr medium sandwiched between two
      metallic slabs. The obtained relation is then simplified to the case of small
      field intensities, while retaining nonlinear terms, to derive approximate
      dispersion equations for the symmetric and antisymmetric SPP modes.

PMID- 21886216
TI  - Interdigitated coplanar electrodes for enhanced sensitivity in a photorefractive
      polymer.
AB  - Organic photorefractive polymer composites can be made to exhibit near 100%
      diffraction efficiency and fast writing times, though large external slants are
      needed to project the applied field onto the grating vector. We show here that
      the use of interdigitated electrodes on a single plane provides similar
      performance to these standard devices and geometries but without a external slant
      angle. This new device's structure also greatly improves the diffraction
      efficiency and sensitivity compared to less slanted standard devices necessary
      for some real applications, such as holographic displays, optical coherence
      imaging, and in-plane switching.

PMID- 21886217
TI  - Higher-order interference of low-coherence optical fiber sensors.
AB  - The higher-order interference noise that is caused by multireflection at the
      fiber sensor's end surface in low-coherence fiber sensor array is proposed. The
      generation of the higher-order interference noise and its quantity and amplitude
      are theoretically analyzed. The second-order interference noises are
      experimentally demonstrated. The results show that the second-order noises arise
      in any sensor array composed of more than two sensors and the number of the
      second-order peaks is proportional to the third power of the sensor's number. The
      ratio of the amplitude of the second-order noise to that of the signal peak is
      proportional to the reflectivity of the sensor's end surface. In a sensor array,
      when the reflectivity is more than 10(-5), the amplitude of the second-order
      noise is higher than other noises and it becomes a main factor that determines
      the signal-to-noise ratio of the sensor arrays. Therefore, reducing the higher
      order interference noise can improve the multiplexing capacity of the sensor
      array.

PMID- 21886218
TI  - Fiber amplification of pulse bursts up to 20 MUJ pulse energy at 1 kHz repetition
      rate.
AB  - We demonstrate burst-mode operation of a polarization-maintaining Yb-doped fiber
      amplifier. Groups of pulses with a temporal spacing of 10 ns and 1 kHz overall
      repetition rate are amplified to an average pulse energy of ~20 MUJ and total
      burst energy of 0.25 mJ. The pulses are externally compressed to ~400 fs. The
      amplifier is synchronously pulsed-pumped to minimize amplified spontaneous
      emission between the bursts. We characterize the influence of pump pulse
      duration, pump-to-signal delay, and signal burst length.

PMID- 21886219
TI  - Phase characterization of the reflection on an extreme UV multilayer: comparison
      between attosecond metrology and standing wave measurements.
AB  - We characterize the phase shift induced by reflection on a multilayer mirror in
      the extreme UV range (80-93 eV) using two techniques: one based on high order
      harmonic generation and attosecond metrology (reconstruction of attosecond
      beating by interference of two-photon transitions), and a second based on
      synchrotron radiation and measurements of standing waves (total electron yield).
      We find an excellent agreement between the results from the two measurements and
      a flat group delay shift (+/-40 as) over the main reflectivity peak of the
      mirror.

PMID- 21886220
TI  - Adaptive optics microscopy with direct wavefront sensing using fluorescent
      protein guide stars.
AB  - We introduce a direct wavefront sensing method using structures labeled with
      fluorescent proteins in tissues as guide stars. An adaptive optics confocal
      microscope using this method is demonstrated for imaging of mouse brain tissue. A
      dendrite and a cell body of a neuron labeled with yellow fluorescent protein are
      tested as guide stars without injection of other fluorescent labels.
      Photobleaching effects are also analyzed. The results shows increased image
      contrast and 3* improvement in the signal intensity for fixed mouse tissues at
      depths of 70 MUm.

PMID- 21886221
TI  - Fully distributed fiber-optic temperature sensing using acoustically-induced
      rocking grating.
AB  - A highly sensitive fully distributed fiber-optic temperature sensing technique is
      proposed and demonstrated based on a transient and traveling rocking grating. The
      rocking grating is generated by pulsed acoustic torsional waves propagating along
      the fiber. The measured temperature sensitivity is 1000 ppm/ degrees C and is
      experimentally demonstrated mainly due to the temperature dependence of the fiber
      birefringence. This traveling rocking grating based sensing technique may also
      serve other fully-distributed sensing applications by using specially designed
      fibers.

PMID- 21886222
TI  - Direct laser writing of near-IR step-index buried channel waveguides in rare
      earth doped YAG.
AB  - A new (to our knowledge) ultrashort laser pulse irradiation regime that allows us
      to directly modify and increase the refractive index of rare earth doped YAG
      polycrystalline ceramics has been identified. Single-mode buried channel
      waveguides in both Ho:YAG and Er:YAG ceramics at the near-IR wavelengths of 1.55
      MUm and 1.95 MUm are demonstrated by fabricating positive square step-index
      cores. Minimum propagation losses of 1.5 dB cm(-1) at a 1.51 MUm wavelength have
      been preliminarily obtained. Confocal microluminescence mapping reveals that the
      increased refractive index regions retain the near-IR spectral properties of Er3+
      ions in the YAG crystalline matrix.

PMID- 21886223
TI  - Octave-spanning frequency comb generation in a silicon nitride chip.
AB  - We demonstrate a frequency comb spanning an octave via the parametric process of
      cascaded four-wave mixing in a monolithic, high-Q silicon nitride microring
      resonator. The comb is generated from a single-frequency pump laser at 1562 nm
      and spans 128 THz with a spacing of 226 GHz, which can be tuned slightly with the
      pump power. In addition, we investigate the RF amplitude noise characteristics of
      the parametric comb and find that the comb can operate in a low-noise state with
      a 30 dB reduction in noise as the pump frequency is tuned into the cavity
      resonance.

PMID- 21886224
TI  - Direct imaging of localized surface plasmon polaritons.
AB  - In this Letter, we report on dark field imaging of localized surface plasmon
      polaritons (SPPs) in plasmonic waveguiding bands formed by plasmonic coupled
      cavities. We image the light scattered from SPPs in the plasmonic cavities
      excited by a tunable light source. Tuning the excitation wavelength, we measure
      the localization and dispersion of the plasmonic cavity mode. Dark field imaging
      has been achieved in the Kretschmann configuration using a supercontinuum white
      light laser equipped with an acoustooptic tunable filter. Polarization dependent
      spectroscopic reflection and dark field imaging measurements are correlated and
      found to be in agreement with finite-difference time-domain calculations.

PMID- 21886225
TI  - Spatial coherence of random laser emission.
AB  - We experimentally studied the spatial coherence of random laser emission from dye
      solutions containing nanoparticles. The spatial coherence, measured in a double
      slit experiment, varied significantly with the density of scatterers and the size
      and shape of the excitation volume. A qualitative explanation is provided,
      illustrating the dramatic difference from the spatial coherence of a conventional
      laser. This work demonstrates that random lasers can be controlled to provide
      intense, spatially incoherent emission for applications in which spatial cross
      talk or speckle limit performance.

PMID- 21886226
TI  - Jaynes-Cummings photonic superlattices.
AB  - A classical realization of the Jaynes-Cummings (JC) model, describing the
      interaction of a two-level atom with a quantized cavity mode, is proposed based
      on light transport in engineered waveguide superlattices. The optical setting
      enables us to visualize in Fock space dynamical regimes not yet accessible in
      quantum systems, providing new physical insights into the deep strong coupling
      regime of the JC model. In particular, bouncing of photon number wave packets in
      Hilbert space and revivals of populations are explained as generalized Bloch
      oscillations in an inhomogeneous tight-binding lattice.

PMID- 21886227
TI  - Near-field spatial correlations from partially coherent homogeneous planar
      sources: effects on surface wave excitation.
AB  - We show that an increase of the coherence length of a statistically homogeneous
      planar source diminishes the contribution of surface waves to the spatial
      coherence of the near field, as well as producing changes in the enhancement of
      the near-field spectrum.

PMID- 21886228
TI  - Slow-light enhanced correlated photon pair generation in a silicon photonic
      crystal waveguide.
AB  - We report the generation of correlated photon pairs in the telecom C-band at room
      temperature from a dispersion-engineered silicon photonic crystal waveguide. The
      spontaneous four-wave mixing process producing the photon pairs is enhanced by
      slow-light propagation enabling an active device length of less than 100 MUm.
      With a coincidence to accidental ratio of 12.8 at a pair generation rate of 0.006
      per pulse, this ultracompact photon pair source paves the way toward scalable
      quantum information processing realized on-chip.

PMID- 21886229
TI  - Theoretical study on photonic devices based on a commensurate two-pattern
      photonic crystal.
AB  - In two-dimensional optical chip applications, the optical wave is classified to
      two modes according to its polarization: TE and TM. It is desirable to integrate
      multiple optical wave control devices for different polarizations onto the same
      plane at the scale of the wavelength. Here we demonstrate a periodic two-pattern
      photonic crystal with a large, complete photonic bandgap (PBG). It comes from the
      superposition of two substructures: one contributes the TM PBG and the other
      contributes the TE PBG. By purposely introducing defects into the substructures,
      photonic devices for different polarizations can be integrated to bend, split,
      and resonate TM/TE waves simultaneously on the same plane.

PMID- 21886230
TI  - Aerosol lenses propagation model.
AB  - We propose a model based on the properties of cascading lenses modulation
      transfer function (MTF) to reproduce the irradiance of a screen illuminated
      through a dense aerosol cloud. In this model, the aerosol cloud is broken into
      multiple thin layers considered as individual lenses. The screen irradiance
      generated by these individual layers is equivalent to the point-spread function
      (PSF) of each aerosol lens. Taking the Fourier transform of the PSF as a MTF, we
      cascade the lenses MTF to find the cloud MTF. The screen irradiance is found with
      the Fourier transform of this MTF. We show the derivation of the model and we
      compare the results with the Undique Monte Carlo simulator for four aerosols at
      three optical depths. The model is in agreement with the Monte Carlo for all the
      cases tested.

PMID- 21886231
TI  - Design of a symmetric blazed grating sheet embedded in an autostereoscopic
      display.
AB  - This study proposes a diffractive autostereoscopic display technology that
      utilizes blazed grating embedded in the liquid crystal panel to deliver a stereo
      image pair to both eyes. Having the diffractive red green blue beams as the color
      source of the panel, color filters are no longer required in this system. From
      the simulation analyses, not only could the brightness achieve 77.90%, but no
      serious chromatic aberration or cross talk appeared.

PMID- 21886232
TI  - Fiber-optic sensor for liquid level measurement.
AB  - A novel (to the best of our knowledge) liquid level sensor based on multimode
      interference (MMI) effects is proposed and demonstrated. By using a multimode
      fiber (MMF) without cladding, known as no-core fiber, liquids around the MMF
      modify the self-imaging properties of the MMI device and the liquid level can be
      detected. We show that the sensor exhibits a highly linear response with the
      sensing range and multiplexed operations easily controlled by just modifying the
      length of the no-core fiber. At the same time, we can measure the refractive
      index of the liquid based on the maximum peak wavelength shift. We can also use
      the sensor for continuous and discrete liquid level sensing applications, thus
      providing a liquid level sensor that is inexpensive with a very simple
      fabrication process.

PMID- 21886233
TI  - Single-pass high-harmonic generation at 20.8 MHz repetition rate.
AB  - We report on single-pass high-harmonic generation (HHG) with amplified driving
      laser pulses at a repetition rate of 20.8 MHz. An Yb:YAG Innoslab amplifier
      system provides 35 fs pulses with 20 W average power at 1030 nm after external
      pulse compression. Following tight focusing into a xenon gas jet, we observe the
      generation of high-harmonic radiation of up to the seventeenth order. Our results
      show that state-of-the-art amplifier systems have become a promising alternative
      to cavity-assisted HHG for applications that require high repetition rates, such
      as frequency comb spectroscopy in the extreme UV.

PMID- 21886234
TI  - Tunable nonlinear absorption of hydrogenated nanocrystalline silicon.
AB  - Nonlinear absorption (NLA) of hydrogenated nanocrystalline silicon (nc-Si:H) has
      been investigated through the open aperture Z-scan method for the photon energy
      of the incident irradiance slightly less than the bandgap of the sample. NLA
      responses have been observed to be highly sensitive to the wavelength and
      intensity of the incident irradiance as well as to the bandgap of the sample,
      indicating greatly tunable NLA of nc-Si:H. The band tail of nc-Si:H appears to
      play a crucial role in such NLA responses.

PMID- 21886235
TI  - Deformable two-dimensional photonic crystal slab for cavity optomechanics.
AB  - We have designed photonic crystal suspended membranes with optimized optical and
      mechanical properties for cavity optomechanics. Such resonators sustain vibration
      modes in the megahertz range with quality factors of a few thousand. Thanks to a
      two-dimensional square lattice of holes, their reflectivity at normal incidence
      at 1064 nm reaches values as high as 95%. These two features, combined with the
      very low mass of the membrane, open the way to the use of such periodic
      structures as deformable end mirrors in Fabry-Perot cavities for the
      investigation of cavity optomechanical effects.

PMID- 21886236
TI  - Tunable third-harmonic generation in a solid-core tellurite glass fiber.
AB  - A solid-core tellurite glass fiber with 1.8 dB/m loss at 1.55 MUm was made by
      using the built-in casting preform fabrication method and rod-in-tube fiber
      drawing technique. Pumping a 10 cm fiber piece with picosecond pulses of 3
      5*10(12) W/cm(2), 0.1% of the fundamental power limited by the coherence length
      of 0.3-5 MUm was converted into visible third-harmonic power tunable over a broad
      near-IR wavelength ranging from 1500 to 1680 nm. Frequency conversion from the
      mid-IR to near-IR was found to be even more efficient due to the longer coherence
      lengths of 12-20 MUm in the wavelength range of 2200-2500 nm.

PMID- 21886237
TI  - Modeling of near-field optical diffraction from a subwavelength aperture in a
      thin conducting film.
AB  - A theoretical model, novel to our knowledge, to investigate the near-field
      optical diffraction from a subwavelength aperture in a thin conducting film is
      presented. A governing equation for the magnetic field distribution in an optical
      thin film based on the power flow theorem is derived for the first time. Thus all
      of the components of the electric and magnetic fields inside or outside the thin
      film with a subwavelength aperture embedded can be obtained by applying the
      Hankel transform accurately. Numerical computations are performed to illustrate
      the edge effect by an enhancement factor of 2.2 and the depolarization phenomenon
      of the transmission in terms of the distance from the film surface.

PMID- 21886238
TI  - Enhancing the linear absorption and tuning the nonlinearity of TiO2 nanowires
      through the incorporation of Ag nanoparticles.
AB  - We report on the enhanced linear absorption and modified nonlinear absorption of
      TiO2 nanowires coated with Ag nanoparticles. Experimental results indicated that
      the coated Ag nanoparticles significantly increased the linear absorption of the
      nanostructures in the wavelength range of visible light. Z-scan experiments
      showed that when the excitation energy increased, the nonlinear absorption of the
      TiO2 nanowires changed from reverse-saturable absorption to saturable absorption.
      When Ag nanoparticles were coated on the TiO2 nanowires, the reverse-saturable
      absorption was significantly inhibited. The as-prepared nanostructures may find
      potential applications in the field of solar cells and all-optical switching.

PMID- 21886239
TI  - Spectral method for characterization of avalanche photodiode working as single
      photon detector.
AB  - In this Letter, a new method for avalanche photodiode characterization, based on
      the spectral analysis of the photocurrent produced during an avalanche, is
      proposed. The theory is developed, and an experimental characterization of an
      avalanche photodiode working in the Geiger mode with CW laser is performed.

PMID- 21886240
TI  - All-optical probing of the nonlinear acoustics of a crack.
AB  - Experiments with an all-optical method for the study of the nonlinear acoustics
      of cracks in solids are reported. Nonlinear acoustic waves are initiated by the
      absorption of radiation from a pair of laser beams intensity modulated at two
      different frequencies. The detection of acoustic waves at mixed frequencies,
      absent in the frequency spectrum of the heating lasers, by optical interferometry
      or deflectometry provides unambiguous evidence of the elastic nonlinearity of the
      crack. The high contrast in crack imaging achieved by remote optical monitoring
      of the nonlinear acoustic processes is due to the strong dependence of the
      efficiency of optoacoustic conversion on the state of the crack. The highest
      acoustic nonlinearity is observed in the transitional state of the crack, which
      is intermediate between the open and the closed ones.

PMID- 21886241
TI  - Excitation and interrogation of whispering-gallery modes in optical
      microresonators using a single fused-tapered fiber tip.
AB  - We show that whispering-gallery modes (WGMs) in optical microresonators can be
      excited and detected using a fused-tapered fiber tip (FTFT). The fabrication of
      FTFTs is simple and inexpensive; they are robust and allow the excitation and
      interrogation of the resonances with a single fiber. Excitation of high-Q WGMs in
      silica microcylinders and microspheres is demonstrated.

PMID- 21886242
TI  - Unifying intensity noise and second-order coherence properties of amplified
      spontaneous emission sources.
AB  - We present joint investigations of relative intensity noise (RIN) and second
      order coherence properties of amplified spontaneous emission (ASE) generated by a
      superluminescent diode. We introduce a generalized intensity noise description
      for ASE sources that contains the shot noise contribution but also accounts for
      first- and second-order coherence properties reflecting the process of light
      generation. We find excellent agreement between pump-current-dependent RIN values
      and this new description, with the perspective of particular interesting
      consequences for the realization of low-noise broadband emitters.

PMID- 21886243
TI  - Demonstration of soft x-ray laser of Ne-like Ar at 69.8 nm pumped by capillary
      discharge.
AB  - The demonstration of a 69.8 nm laser on 3p 3P2 - 3s 1P1 (J=2-1) transition of Ne
      like Ar pumped by capillary discharge is reported in this Letter. A main current
      of 12 kA with rise time of 43 ns was chosen to generate the plasma in a 35 cm
      long capillary filling with pressure of Ar as low as 11 Pa, resulting in a gain
      coefficient of 0.34 cm(-1) and gain-length product of 11 at 69.8 nm. Also
      observed is a weak laser on 3p 3D2 - 3s 3P1 (J=2-1) transition of Ne-like Ar at
      72.6 nm in the same condition. In addition, multiwavelength lasing at 46.9, 69.8,
      and 72.6 nm was simultaneously realized in a capillary discharge plasma column,
      conditioning the pressure of Ar to 13 Pa.

PMID- 21886244
TI  - Optimal design for hollow fiber inner-coated by dielectric layers with surface
      roughness.
AB  - We report the optimal design for hollow fiber inner-coated with metallic and
      multidielectric layers by using ray-optics theory. Transmission characteristics
      of the multilayer hollow fiber are more dependent on the film surface roughness
      in the IR region. Comparisons of fibers with smooth and rough films are made and
      discussed in detail. The optimal design for film thickness, inner radius, and the
      number of layers and refractive indices is presented. The calculation results are
      important for structure design, material selection, and fabrication when
      considering imperfections in film-coating techniques. Multilayer fibers are
      fabricated based on the calculation and experimental results agree with the
      theoretical ones.

PMID- 21886245
TI  - Micromirror with large-tilting angle using Fe-based metallic glass.
AB  - For enhancing the micromirror properties like tilting angle and stability during
      actuation, Fe-based metallic glass (MG) was applied for torsion bar material. A
      micromirror with mirror-plate diameter of 900 MUm and torsion bar dimensions
      length 250 MUm, width 30 MUm and thickness 2.5 MUm was chosen for the tilting
      angle tests, which were performed by permanent magnets and electromagnet setup.
      An extremely large tilting angle of over -270 degrees  was obtained from an
      activation test by permanent magnet that has approximately 0.2 T of magnetic
      strength. A large mechanical tilting angle of over -70 degrees  was obtained by
      applying approximately 1.1 mT to the mirror when 93 mAwas applied to solenoid
      setup. The large-tilting angle of the micromirror is due to the torsion bar,
      which was fabricated with Fe-based MG thin film that has large elastic strain
      limit, fracture toughness, and excellent magnetic property.

PMID- 21886246
TI  - High-efficiency frequency doubling of continuous-wave laser light.
AB  - We report on the observation of high-efficiency frequency doubling of 1550 nm
      continuous-wave laser light in a nonlinear cavity containing a periodically poled
      potassium titanyl phosphate crystal (PPKTP). The fundamental field had a power of
      1.10 W and was converted into 1.05 W at 775 nm, yielding a total external
      conversion efficiency of 95+/-1%. The latter value is based on the measured
      depletion of the fundamental field being consistent with the absolute values
      derived from numerical simulations. According to our model, the conversion
      efficiency achieved was limited by the nonperfect mode matching into the
      nonlinear cavity and by the nonperfect impedance matching for the maximum input
      power available. Our result shows that cavity-assisted frequency conversion based
      on PPKTP is well suited for low-decoherence frequency conversion of quantum
      states of light.

PMID- 21886247
TI  - Solitons in geometric potentials.
AB  - We show that the geometrically induced potential existing in undulated slab
      waveguides dramatically affects the properties of solitons. In particular,
      whereas solitons residing in the potential maxima do not feature power thresholds
      and are stable, their counterparts residing in the potential minima are unstable
      and may exhibit a power threshold for their existence. Additionally, the
      geometric potential is shown to support stable multipole solitons that cannot be
      supported by straight waveguides. Finally, the geometric potential results in the
      appearance of the effective barriers that prevent transverse soliton motion.

PMID- 21886248
TI  - Optical switching and detection of 640 Gbits/s optical time-division multiplexed
      data packets transmitted over 50 km of fiber.
AB  - We demonstrate 1*4 optical-packet switching with error-free transmission of 640
      Gbits/s single-wavelength optical time-division multiplexed data packets
      including clock distribution and short pulse generation for optical time
      demultiplexing based on a cavityless pulse source.

PMID- 21886249
TI  - Polarization insensitive, broadband terahertz metamaterial absorber.
AB  - We present the simulation, implementation, and measurement of a polarization
      insensitive broadband resonant terahertz metamaterial absorber. By stacking metal
      insulator layers with differing structural dimensions, three closely positioned
      resonant peaks are merged into one broadband absorption spectrum. Greater than
      60% absorption is obtained across a frequency range of 1.86 THz where the central
      resonance frequency is 5 THz. The FWHM of the device is 48%, which is two and
      half times greater than the FWHM of a single layer structure. Such metamaterials
      are promising candidates as absorbing elements for bolometric terahertz imaging.

PMID- 21886250
TI  - Nondiffracting transversally polarized beam.
AB  - Generation of a nondiffracting transversally polarized beam by means of
      transmitting an azimuthally polarized beam through a multibelt spiral phase
      hologram and then highly focusing by a high-NA lens is presented. A relatively
      long depth of focus (~4.84lambda) of the electric field with only radial and
      azimuthal components is achieved. The polarization of the wavefront near the
      focal plane is analyzed in detail by calculating the Stokes polarization
      parameters. It is found that the polarization is spatially varying and entirely
      transversally polarized, and the polarization singularity disappears at the beam
      center, which makes the central bright channel possible.

PMID- 21886251
TI  - Simplified expressions of the T-matrix integrals for electromagnetic scattering.
AB  - The extended boundary condition method, also called the null-field method,
      provides a semianalytic solution to the problem of electromagnetic scattering by
      a particle by constructing a transition matrix (T-matrix) that links the
      scattered field to the incident field. This approach requires the computation of
      specific integrals over the particle surface, which are typically evaluated
      numerically. We introduce here a new set of simplified expressions for these
      integrals in the commonly studied case of axisymmetric particles. Simplifications
      are obtained using the differentiation properties of the radial functions
      (spherical Bessel) and angular functions (associated Legendre functions) and
      integrations by parts. The resulting simplified expressions not only lead to
      faster computations, but also reduce the risks of loss of precision and provide a
      simpler framework for further analytical work.

PMID- 21886252
TI  - Two-step interferometry by a regularized optical flow algorithm.
AB  - A two-step phase-shifting method, that can demodulate open- and closed-fringed
      patterns without local sign ambiguity is presented. The proposed method only
      requires a constant phase-shift between the two interferograms. This phase-shift
      does not need to be known and can take any value inside the range (0, 2pi),
      excluding the singular case where it corresponds to pi. The proposed method is
      based on determining first the fringe direction map by a regularized optical flow
      algorithm. After that, we apply the spiral phase transform (SPT) to one of the
      fringe patterns and we determine its quadrature signal using the previously
      determined direction. The proposed technique has been applied to simulated and
      experimental interferograms obtaining satisfactory results. A complete MATLAB
      software package is provided in [http://goo.gl/Snnz7].

PMID- 21886253
TI  - Bottle microresonator with actively stabilized evanescent coupling.
AB  - The evanescent coupling of light between a whispering-gallery-mode bottle
      microresonator and a subwavelength-diameter coupling fiber is actively stabilized
      by means of the Pound-Drever-Hall technique. We demonstrate the stabilization of
      a critically coupled resonator with a control bandwidth of 0.1 Hz, yielding a
      residual transmission of (9+/-3)*10(-3) for more than an hour. Simultaneously,
      the frequency of the resonator mode is actively stabilized.

PMID- 21886254
TI  - Real-time digital holographic microscopy of multiple and arbitrarily oriented
      planes.
AB  - Digital holographic microscopy is used to numerically refocus a recorded hologram
      at an arbitrary axial distance. However, as a straightforward property of
      coherent light fields, image reconstruction on an arbitrary tilted plane could be
      directly obtained by a rotation in k-space. We demonstrate that this property
      allows the real-time microscopic inspection of particle distribution over three
      mutually orthogonal planes at the same time. As a straightforward application we
      use the proposed technique for real-time monitoring of fluid flow over the three
      cross sections of a microfluidic channel.

PMID- 21886255
TI  - Compensation of phase-to-amplitude modulation conversion in a complete frequency
      conversion system with an all-fiber system.
AB  - We report on an experimental demonstration of linear precompensation of nonlinear
      phase and amplitude transfer functions. We show the effective compensation with a
      linear all-fiber system of phase-to-amplitude modulation conversion due to a
      complete frequency conversion system including plane gratings and a nonlinear
      crystal.

PMID- 21886256
TI  - Impact of unpredictability on chaos synchronization of vertical-cavity surface
      emitting lasers with variable-polarization optical feedback.
AB  - The effects of unpredictability degree on the chaos synchronization properties of
      vertical-cavity surface-emitting lasers with variable-polarization optical
      feedback are investigated numerically. For variable-polarization optical
      injection, only low-unpredictability chaos can be well synchronized, while high
      unpredictability chaos cannot be synchronized even with large injection strength.
      On the other hand, for the polarization-preserved optical injection, the
      synchronization quality is hardly affected by the unpredictability degree, and
      high-quality synchronization can be achieved for both low- and high
      unpredictability chaos due to injection locking.

PMID- 21886257
TI  - Numerical investigation on the enhanced carrier collection efficiency of Ga-face
      GaN/InGaN p-i-n solar cells with polarization compensation interlayers.
AB  - The impact of the polarization compensation InGaN interlayer between the
      heterolayers of Ga-face GaN/InGaN p-i-n solar cells is investigated numerically.
      Because of the enhancement of carrier collection efficiency, the conversion
      efficiency is improved markedly, which can be ascribed to both the reduction of
      the polarization-induced electric field in the InGaN absorption layer and the
      mitigation of potential barriers at heterojunctions. This beneficial effect is
      more remarkable in situations with higher polarization, such as devices with a
      lower degree of relaxation or devices with a higher indium composition in the
      InGaN absorption layer.

PMID- 21886258
TI  - Three-dimensional in vivo scanning microscopy with inertia-free focus control.
AB  - The acquisition of high-resolution images in three dimensions is of utmost
      importance for the morphological and functional investigation of biological
      tissues. Here, we present a laser scanning two-photon microscope with remote and
      motionless control of the focus position. The movement of the excitation spot
      along the propagation direction is achieved by shaping the laser wavefront with a
      spatial light modulator. Depending on the optical properties of the objective in
      use, this approach allows z movements in a range of tens to hundreds of
      micrometers with small changes of the point spread function. We applied this
      technique for the three-dimensional (3D) imaging of fluorescent cells in the
      mouse neocortex in vivo. The presented system bypasses the limitations of
      microscopes based on moving objectives, enabling high-resolution inertia-free 3D
      imaging.

PMID- 21886259
TI  - Selective polarization mode excitation in InGaAs/GaAs microtubes.
AB  - We report on selective polarization mode excitation in InGaAs/GaAs rolled-up
      microtubes. The microtubes are fabricated by selectively releasing a coherently
      strained InGaAs/GaAs quantum dot layer from its host GaAs substrate. An optical
      fiber abrupt taper is used to pick up the microtube, while an adiabatically
      tapered optical fiber is used to couple light into the resonant optical modes of
      the microtube. By varying the polarization of the light in the adiabatically
      tapered fiber both transverse electric and transverse magnetic modes are observed
      in the microtube. We also show that the microtube can be used as a red (0.6 MUm)
      to infrared light (1.5 MUm) optical-optical modulator taking advantage of the
      thermal-optical effect.

PMID- 21886260
TI  - Temporal differentiation of optical signals using resonant gratings.
AB  - We study theoretically the possibility of performing temporal differentiation of
      optical signals using a resonant diffraction grating. We demonstrate that the
      resonant grating allows the calculation of the first-order derivative of an
      optical signal envelope in the vicinity of waveguide resonant frequencies in the
      zeroth transmitted diffraction order. The grating is shown to allow the
      calculation of the fractional derivative of order 1/2 in the vicinity of Rayleigh
      Wood anomalies. Numerical simulations based on the rigorous coupled-wave analysis
      of Maxwell's equations demonstrate the high-quality differentiation of optical
      signals with temporal features in the picosecond range.

PMID- 21886261
TI  - Sculptured 3D twister superlattices embedded with tunable vortex spirals.
AB  - We present diverse reconfigurable complex 3D twister vortex superlattice
      structures in a large area embedded with tunable vortex spirals as well as dark
      rings, threaded by vortex helices. We demonstrate these tunable complex chiral
      vortex superlattices by the superposition of relatively phase engineered plane
      waves. The generated complex 3D twister lattice vortex structures are
      computationally as well as experimentally analyzed using various tools to verify
      the presence of phase singularities. Our observation indicates the application
      specific flexibility of our approach to tailor the transverse superlattice
      spatial irradiance profile of these longitudinally whirling vortex-cluster units
      and dark rings.

PMID- 21886262
TI  - Optical bistability in GaInAsP/InP coupled-circular resonator microlasers.
AB  - Optical bistability is realized in GaInAsP/InP coupled-circular resonator
      microlasers, which are fabricated by planar technology. For a coupled-circular
      resonator microlaser with the radius of 20 MUm and a 2 MUm-wide bus waveguide,
      hysteresis loops are observed for the output power coupling into an optical fiber
      versus the cw injection current at room temperature. The laser output spectra of
      the upper and lower states of the hysteresis loop indicate that the bistability
      is related to mode competitions. The optical bistability can be explained as the
      mode competition between the symmetry and antisymmetry coupled modes relative to
      the bus waveguide.

PMID- 21886263
TI  - Tunable chirped microwave photonic filter employing a dispersive Mach-Zehnder
      structure.
AB  - A Mach-Zehnder structure with modulation in one arm and dispersive time delay in
      the other is proposed to implement highly flexible single-bandpass chirped
      microwave photonic filters based on broadband optical sources. Both the amplitude
      response and the time delay slope can be fully reconfigured via control of the
      optical spectra and dispersion. The passband can also be widely tuned without
      changing the shape. A chirped filter with a bandwidth of ~4 GHz, a delay slope of
      ~-0.6 ns/GHz, and a tunability up to 40 GHz is demonstrated experimentally.

PMID- 21886264
TI  - High Q silica microbubble resonators fabricated by arc discharge.
AB  - Microbubble resonators combine the unique properties of whispering gallery mode
      resonators with the intrinsic capability of integrated microfluidics. Here an
      improved fabrication method of microbubble resonators is presented, based on the
      heating of a slightly pressurized capillary by a rotating arc discharge. Rotation
      of the electrodes, moved out of a fiber splicer, ensures a homogeneous
      distribution of the heat all over the capillary surface. The demonstrated
      microbubble resonators have Q factors up to 6*10(7) at 1550 nm. Microbubbles were
      filled with water and aqueous solutions of ethanol in order to test the
      refractive index sensing capabilities of such resonators, which also show a good
      temporal stability. The limit of detection of our microbubble resonator sensor is
      10(-6) RIU.

PMID- 21886265
TI  - Polarization-independent on-axis light coupler for surface plasmon resonance
      using a concentric chirped grating.
AB  - A novel on-axis one-element polarization-independent light in- and out-coupling
      mechanism for surface plasmon resonance (SPR) is proposed. The system utilizes an
      integrated high-NA concentric chirped grating to both focus the incident light on
      the metallic film and collimate the reflected beam onto a CCD array to extract
      the SPR signal. With NA up to 1.47, a broad sensing dynamic range from n=1 to
      1.35 can be achieved. An analytical model is implemented to demonstrate the
      dependency of the radial location of the resonances on the detecting substance
      and its sensitivity to the change of the refractive index. The model shows a
      trend similar to rigorous ray-tracing calculations.

PMID- 21886266
TI  - Near-field coupling of metal nanoparticles under tightly focused illumination.
AB  - The influence of strongly focused radiation on the electromagnetic interaction of
      metal particles is studied. The near-field distribution of silver dimers is
      calculated by combining a multiple scattering approach and the multipolar
      expansion of focused beams based on the Richards-Wolf description of diffracting
      systems. The results show that tight focusing can induce larger maximum field
      enhancement and stronger localization of the near field than can plane wave
      illumination. Additional plasmonic resonances can be obtained due to the presence
      of different polarization contributions at focus.

PMID- 21886267
TI  - High-order harmonic generation enhanced by XUV light.
AB  - The combination of high-order harmonic generation (HHG) with resonant XUV
      excitation of a core electron into the transient valence vacancy that is created
      in the course of the HHG process is investigated theoretically. In this setup,
      the first electron performs a HHG three-step process, whereas the second electron
      Rabi flops between the core and the valence vacancy. The modified HHG spectrum
      due to recombination with the valence and the core is determined and analyzed for
      krypton on the 3d->4p resonance in the ion. We assume an 800 nm laser with an
      intensity of about 10(14) W/cm2 and XUV radiation from the Free Electron Laser in
      Hamburg (FLASH) with an intensity in the range 10(13)-10(16)W cm2. Our prediction
      opens perspectives for nonlinear XUV physics, attosecond x rays, and HHG-based
      spectroscopy involving core orbitals.

PMID- 21886268
TI  - Mitochondrial Death Channels.

PMID- 21886269
TI  - The Temporal Structure of Scientific Consensus Formation.
AB  - This article engages with problems that are usually opaque: What trajectories do
      scientific debates assume, when does a scientific community consider a
      proposition to be a fact, and how can we know that? We develop a strategy for
      evaluating the state of scientific contestation on issues. The analysis builds
      from Latour's black box imagery, which we observe in scientific citation
      networks. We show that as consensus forms, the importance of internal divisions
      to the overall network structure declines. We consider substantive cases that are
      now considered facts, such as the carcinogenicity of smoking and the non
      carcinogenicity of coffee. We then employ the same analysis to currently
      contested cases: the suspected carcinogenicity of cellular phones, and the
      relationship between vaccines and autism. Extracting meaning from the internal
      structure of scientific knowledge carves a niche for renewed sociological
      commentary on science, revealing a typology of trajectories that scientific
      propositions may experience en route to consensus.

PMID- 21886270
TI  - Probing the physiology of ASH neuron in Caenorhabditis elegans using electric
      current stimulation.
AB  - Electrical stimulation has been widely used to modulate and study the in vitro
      and in vivo functionality of the nervous system. Here, we characterized the
      effect of electrical stimulation on ASH neuron in Caenorhabditis elegans and
      employed it to probe the neuron's age dependent properties. We utilized an
      automated microfluidic-based platform and characterized the ASH neuronal activity
      in response to an electric current applied to the worm's body. The electrically
      induced ASH neuronal response was observed to be dependent on the magnitude,
      polarity, and spatial location of the electrical stimulus as well as on the age
      of the worm.

PMID- 21886271
TI  - John J. Triano, DC, PhD.

PMID- 21886272
TI  - The Chiropractic dilemma. To be isolated or integrated?

PMID- 21886273
TI  - The long term survival of chiropractic: involvement and research.

PMID- 21886274
TI  - Research - preparing for tomorrow!

PMID- 21886275
TI  - Incident Reporting and Learning Systems for chiropractors - Developments in
      Europe.

PMID- 21886276
TI  - It was my understanding that there would be no math.

PMID- 21886277
TI  - Does chiropractic truly understand research?

PMID- 21886278
TI  - Interprofessional education for medical students in clinical settings: a
      practical guide for an elective half-day.

PMID- 21886279
TI  - Baseline knowledge on vehicle safety and head restraints among Fleet Managers in
      British Columbia Canada: a pilot study.
AB  - BACKGROUND: Whiplash is the most common injury type arising from motor vehicle
      collisions, often leading to long-term suffering and disability. Prevention of
      such injuries is possible through the use of appropriate, correctly positioned,
      vehicular head restraints. OBJECTIVE: To survey the awareness and knowledge level
      of vehicle fleet managers in the province of British Columbia, Canada, on the
      topics of vehicle safety, whiplash injury, and prevention; and to better
      understand whether these factors influence vehicle purchase/lease decisions.
      METHODS: A survey was administered to municipal vehicle fleet managers at a
      professional meeting (n = 27). RESULTS: Although many respondents understood the
      effectiveness of vehicle head restraints in the prevention of whiplash injury,
      the majority rarely adjusted their own headrests. Fleet managers lacked knowledge
      about the seriousness of whiplash injuries, their associated costs for Canada's
      healthcare system, and appropriate head restraint positions to mitigate such
      injuries. The majority of respondents indicated that fleet vehicle purchase/lease
      decisions within their organization did not factor whiplash prevention as an
      explicit safety priority. CONCLUSIONS: There is relatively little awareness and
      enforcement of whiplash prevention strategies among municipal vehicle fleet
      managers.

PMID- 21886280
TI  - The effect of spinal manipulation on imbalances in leg strength.
AB  - We hypothesized that spinal manipulation (SM) would reduce strength imbalances
      between legs. Using an un-blinded randomized design, 28 males and 21 females (54
      +/- 19y) with at least a 15% difference in isometric strength between legs for
      hip flexion, extension, abduction, or knee flexion were randomized to treatment
      or placebo (mock spinal manipulation). Strength of the stronger and weaker legs
      for hip flexion, extension, abduction, and/or knee flexion was assessed before
      and after the intervention. SM reduced the relative strength difference between
      legs for knee flexion (mean +/- SD 57 +/- 53 to 5 +/- 14%) and hip flexion (24 +/
      12 to 11 +/- 15%) compared to placebo (34 +/- 29 to 24 +/- 36%, and 20 +/- 18 to
      22 +/- 26%, respectively) (p = 0.05). SM also improved strength in the weak leg
      for hip abduction (104 +/- 43 to 116 +/- 43 Nm) compared to placebo (84 +/- 24 to
      85 +/- 31 Nm) (p = 0.03). This study suggests that spinal manipulation may reduce
      imbalances in strength between legs for knee and hip flexion.

PMID- 21886281
TI  - Perceived effects of the delisting of chiropractic services from the Ontario
      Health Insurance Plan on practice activities: a survey of chiropractors in
      Toronto, Ontario.
AB  - The purpose of this study was to survey a random sample of Toronto chiropractors
      and gather their perceptions of the effects that the delisting of chiropractic
      services from OHIP had on their practices profiles. METHODS: A survey was mailed
      to 199 chiropractors who were asked to disclose demographic information, if they
      were in practice at the time when OHIP coverage was in effect, the perceived
      effect OHIP delisting had on their patient volumes, income, the profession's
      credibility and if they would be in favor of having OHIP reinstated. RESULTS:
      Among the 123 respondents in practice during OHIP coverage (n = 92), 48.9%
      indicated they perceived their practice income and 36.6% perceived their patient
      volume was negatively affected; 57.5% reported both had subsequently recovered.
      Almost 50% perceived OHIP delisting negatively affected the profession's
      credibility and 46.1% of respondents were in favor of it being reinstated for
      chiropractic services; this percentage was much higher among chiropractors who
      were not in practice during the time of OHIP coverage. CONCLUSION: Most
      chiropractors reported that patient volumes and incomes have returned to pre
      delisting levels and few chiropractors who were in practice during OHIP coverage
      expressed interest in having it reinstated.

PMID- 21886282
TI  - Amyotrophic lateral sclerosis presenting as upper limb weakness in a 35 year old
      female: a case report.
AB  - Chiropractors regularly assess and provide treatment for a variety of
      neuromuscular complaints. Many of these respond well to conservative care however
      some represent conditions that must be referred for further evaluation. This
      article chronicles the management of a patient who presented with upper limb
      weakness and was subsequently diagnosed with amyotrophic lateral sclerosis (ALS).
      Chiropractors should be informed of the nature and presentation of this disease
      to facilitate early diagnosis and treatment.

PMID- 21886283
TI  - The association between neck pain, the Neck Disability Index and cervical ranges
      of motion: a narrative review.
AB  - BACKGROUND: The Neck Disability Index (NDI) and Cervical Ranges of Motion (CROM)
      are measurement tools that are used for neck pain patients. OBJECTIVE: To review
      the literature to determine how the NDI is associated with neck pain and CROM
      outcomes. METHODS: Computer based searches of 5 databases were performed and
      supplemented by internet and hand searching of article references and "related
      citations." RESULTS: The search yielded 23 studies that met the inclusion and
      exclusion criteria and these were summarized into four categories: NDI, NDI and
      other questionnaires, whiplash and NDI and cervical range of motion and NDI. The
      NDI was shown to be a well validated and reliable self-reported questionnaire,
      especially when compared to other questionnaires, in both neck pain and whiplash
      (WAD) patients. There are very few studies that discuss the NDI and cervical
      range of motion. CONCLUSION: This review outlines the strength of the NDI as a
      self-reported neck disability questionnaire, but also demonstrates a need for
      further research to explore the association between the NDI, neck pain and
      cervical ranges of motion.

PMID- 21886284
TI  - The Tampa Scale of Kinesiophobia and neck pain, disability and range of motion: a
      narrative review of the literature.
AB  - BACKGROUND: The Tampa Scale of Kinesiophobia (TSK) that was developed in 1990 is
      a 17 item scale originally developed to measure the fear of movement related to
      chronic lower back pain. OBJECTIVE: To review the literature regarding TSK and
      neck pain, perceived disability and range of motion of the cervical spine.
      METHODS: Medline, MANTIS, Index to Chiropractic Literature and CINAHL were
      searched. RESULTS: A total of 16 related articles were found and divided into
      four categories: TSK and Neck Pain; TSK, Neck Pain and Disability; TSK, Neck
      Pain, Disability and Strength; and TSK, Neck Pain and Surface Electromyography.
      CONCLUSION: The fear avoidance model can be applied to neck pain sufferers and
      there is value from a psychometric perspective in using the TSK to assess
      kinesiophobia. Future research should investigate if, and to what extent, other
      measureable factors commonly associated with neck pain, such as decreased range
      of motion, correlate with kinesiophobia.

PMID- 21886285
TI  - Hawai'i Medical Journal. Guest editor's message.

PMID- 21886286
TI  - Adolescent at-risk weight (overweight and obesity) prevalence in Hawai'i.
AB  - OBJECTIVE: To present prevalence rates of adolescents in Hawai'i at-risk weight
      (85 percentile or higher = overweight or obese) and the relationship with
      comorbidities. METHODS: The Hawai'i Youth Risk Behavior Survey aggregated for
      2005, 2007, and 2009 was analyzed addressing at-risk weight prevalence by sex,
      race/ethnicity, and grade. Comorbidities were related to at-risk weight using
      regression. RESULTS: Over 1/4 of Hawai'i adolescents were at-risk weight. There
      were no differences by grade, but boys had higher prevalence (31.0%) than girls
      (22.4%). Overall, Other Pacific Islanders and Hawaiians had the highest
      prevalence (43.9% and 37.4%, respectively), followed by multi-race (27.1%),
      Filipino (25.7%), and Whites with the lowest (16.1%). Most associations between
      at-risk weight and various co-morbidities (including sexual behavior, nutrition,
      physical activity, mental health, bullying, alcohol, and other drug use) were not
      significant (p>.05). However, girls and boys trying to lose weight; and boys with
      3+ hours of screen time (TV, video, or computer games) each day were at increased
      odds of at-risk weight (p<.05). CONCLUSION: Adolescent gender and ethnic
      disparities exist such that a single intervention approach (one size fits all)
      may be counterproductive. More research is required on the determinants and
      mechanisms to guide weight management interventions.

PMID- 21886287
TI  - Perceptions of middle school educators in Hawai'i about school-based gardening
      and child health.
AB  - BACKGROUND: Childhood obesity prevention is a national priority. School-based
      gardening has been proposed as an innovative obesity prevention intervention.
      Little is known about the perceptions of educators about school-based gardening
      for child health. As the success of a school-based intervention depends on the
      support of educators, we investigated perceptions of educators about the benefits
      of gardening programs to child health. METHODS: Semi-structured interviews of 9
      middle school educators at a school with a garden program in rural Hawai'i were
      conducted. Data were analyzed using a grounded theory approach. RESULTS:
      Perceived benefits of school-based gardening included improving children's diet,
      engaging children in physical activity, creating a link to local tradition,
      mitigating hunger, and improving social skills. Poverty was cited as a barrier to
      adoption of healthy eating habits. Opinions about obesity were contradictory;
      obesity was considered both a health risk, as well as a cultural standard of
      beauty and strength. Few respondents framed benefits of gardening in terms of
      health. CONCLUSIONS: In order to be effective at obesity prevention, school-based
      gardening programs in Hawai'i should be framed as improving diet, addressing
      hunger, and teaching local tradition. Explicit messages about obesity prevention
      are likely to alienate the population, as these are in conflict with local
      standards of beauty. Health researchers and advocates need to further inform
      educators regarding the potential connections between gardening and health.

PMID- 21886288
TI  - Poorer general health status in children is associated with being overweight or
      obese in Hawai'i: findings from the 2007 National Survey of Children's Health.
AB  - Obesity is a widespread national issue that affects the health and well-being of
      millions of people; particular attention has been focused on the burden among
      children. The National Survey of Children's Health data from 2007 was used to
      examine the relationship of child health status and unhealthy weight
      (overweight/obese defined as body mass index in >= 85 th percentile) among 874
      children aged 10 to 17 years of age in Hawai'i. In particular, the parentally
      reported child's general health status was assessed comparing those with a poorer
      health status (defined as "good/fair/poor") to those with a better one (defined
      as "excellent/very good"). Descriptive analysis and multiple logistic regression
      analysis examined risk for overweight/obese with child's general health status,
      accounting for gender, race, and socioeconomic factors. More children with a
      poorer health status (46.5%; 95%CI=33.2-60.2) were overweight/obese compared to
      those of better health status (25.8%; 95%CI=21.9-30.2). Estimates of
      overweight/obese were high in Native Hawaiian/Pacific Islander (38.6%; 95%CI:
      28.9-49.4), multiracial (30.9%; 95%CI=24.2-38.6) children, and children whose
      parents had less than 12 years education (56.8%; 95%CI=32.8-78.0). Multivariate
      logistic regression modeling showed a 2.92 (95%CI=1.52-5.61) greater odds for
      overweight/obese status in children with a poorer health status compared to those
      of better health status after accounting for age, race, gender, and parental
      education. Gender, race, and parental education were also significant factors
      associated with overweight/obese in the final adjusted model. It is important
      that children that are overweight or obese receive appropriate health screenings
      including assessments of general health status. Children in high risk
      socioeconomic groups should be a particular focus of prevention efforts to
      promote health equity and provide opportunities for children to reach their
      potential.

PMID- 21886289
TI  - Hawai'i's Opportunity for Active Living Advancement (HO'ALA): addressing
      childhood obesity through safe routes to school.
AB  - Increasing active transportation to and from school may reduce childhood obesity
      rates in Hawai'i. A community partnership was formed to address this issue in
      Hawai'i's Opportunity for Active Living Advancement (HO'ALA), a quasi
      experimental study of active transportation in Hawai'i County. The purpose of
      this study was to determine baseline rates for active transportation rates to and
      from school and to track changes related to macro-level (statewide) policy,
      locally-based Safe Routes to School (SRTS) programs and bicycle and pedestrian
      planning initiatives expected to improve the safety, comfort and ease of walking
      and bicycling to and from school. Measures included parent surveys, student
      travel tallies, traffic counts and safety observations. Assessments of the
      walking and biking environment around each school were made using the Pedestrian
      Environment Data Scan. Complete Streets and SRTS policy implementation was
      tracked through the activities of a state transportation-led Task Force and an
      advocacy-led coalition, respectively. Planning initiatives were tracked through
      citizen-based advisory committees. Thirteen volunteer schools participated as the
      intervention (n=8) or comparison (n=5) schools. The majority of students were
      Asian, Native Hawaiian, and Pacific Islander in schools located in under
      resourced communities. Overall, few children walked or biked to school. The
      majority of children were driven to and from school by their parents. With the
      influence of HO'ALA staff members, two intervention schools were obligated SRTS
      project funding from the state, schools were identified as key areas in the
      pedestrian master plan, and one intervention school was slated for a bike plan
      priority project. As the SRTS programs are implemented in the next phase of the
      project, post-test data will be collected to ascertain if changes in active
      transportation rates occur.

PMID- 21886290
TI  - The prevalence of overweight and obesity in children at a Health Maintenance
      Organization in Hawai'i.
AB  - In the past 20-30 years, the number of overweight children in the United States
      has doubled.1 Overweight children are acquiring conditions such as hypertension,
      type II diabetes, hypercholesterolemia, sleep apnea, and orthopedic problems. The
      purpose of this study was to explore the prevalence of and factors associated
      with at risk and overweight in children 2-10 years of age in a Health Maintenance
      Organization (HMO) in Hawai'i. This quantitative, retrospective cross-sectional
      study included a stratified random sample of 554 children ages 2-10 years who
      received a well child health care exam at a HMO in 2003. The prevalence of at
      risk and overweight were examined including the relationship between ethnicity,
      socioeconomic status, place of residence, and a child being overweight. Thirteen
      percent were at risk for overweight (BMI 85-95%) and 19% (BMI >95%) were
      overweight. In the 6-10 year age group, 42 % were overweight or at risk for being
      overweight. Boys had a higher incidence of being overweight (54%) than the girls
      (46%). Pacific Islanders had the highest incidence of overweight (40%), followed
      by the Hawaiian/Part Hawaiians (19%) and Filipinos (19%). Ethnicity and place of
      residence were significantly associated with being at risk or overweight. Pacific
      Islanders were 4 times more likely to be overweight/at risk for overweight and
      those residing in the West O'ahu, Honolulu, and Central O'ahu/North Shore areas
      were 2-3 times more likely to be at risk for overweight when compared to children
      living in the Windward side. With increased age, the prevalence of overweight
      increased. Findings suggest that targeted obesity prevention strategies need to
      be initiated early in life and geared for ethnically and geographically diverse
      children and their families.

PMID- 21886291
TI  - Race/ethnic differences in desired body mass index and dieting practices among
      young women attending college in Hawai'i.
AB  - In accordance with the sociocultural model, race/ethnicity is considered a major
      influence on factors associated with body image and body dissatisfaction, and
      eating disorders are often characterized as problems that are primarily limited
      to young White women from Western cultures. The purpose of this study was to
      determine whether there are differences that exist by race in desired body
      weight; the importance placed on those ideals; and dieting strategies among
      White, Asian American, Native Hawaiian/Pacific Islanders, and other mixed-race
      young women in Hawai'i. A total of 144 female college students 18-20 years of age
      were surveyed about body weight as well as eating and exercise habits. Results
      demonstrated that all the young women wanted to lose weight. However, there were
      no differences in desired body weight or desired weight change by race after
      controlling for body mass index suggesting that current weight rather than
      race/ethnicity is the predominant influence on weight-related concerns. Young
      White women placed the greatest level of importance on achieving a lower body
      weight, which corresponded with a greater likelihood to be attempting weight loss
      (dieting) and greater endorsement of behaviors consistent with weight loss
      compared to their counterparts. Findings imply that, for young women,
      race/ethnicity may not have as significant an impact on factors associated with
      body weight ideals as previously believed. Rather, differences in the value
      placed on achieving a desired body weight, as it relates to disordered eating,
      should be further explored among race/ethnic groups.

PMID- 21886292
TI  - The impact of an elementary after-school nutrition and physical activity program
      on children's fruit and vegetable intake, physical activity, and body mass index:
      Fun 5.
AB  - OBJECTIVE: This study evaluated the impact of the Fun 5 program on fruit and
      vegetable intake, physical activity, and body mass index (BMI) percentile of
      overweight and obese children in Hawai'i's A+ After-School Program. METHODS:
      Children in 4th - 6th grades (n=119, 55% female) from six randomly selected
      schools participated in this longitudinal study. Time 1 (T1) measures were taken
      October 2007 and time 2 (T2) measures April 2008. Height and weight along with a
      self-report survey were used to measure fruit and vegetable intake, physical
      activity, and BMI. RESULTS: The "at risk" population, defined as fruit and
      vegetable intake <5 servings per day (n=30), physical activity <300 minutes per
      week (n=78), or Body Mass Index >85th percentile (n=48) at T1, showed a
      significant increase in fruit and vegetable intake, from 2.97 (+/- 1.16) servings
      per day at T1 to 5.60 (+/- 3.93) servings per day at T2 (P=<0.01) and physical
      activity, from 125.26 (+/- 76.03) minutes per week of physical activity at T1 to
      222.18 (+/- 180.90) minutes per week at T2 (P=<0.01) and no change in Body Mass
      Index. CONCLUSION: The Fun 5 program had an impact on improving fruit and
      vegetable intake and physical activity on the at risk population.

PMID- 21886293
TI  - Development and implementation of a food system intervention to prevent childhood
      obesity in rural Hawai'i.
AB  - This paper presents details the Healthy Foods Hawai'i (HFH) intervention trial,
      aimed to improve children's dietary behavior to prevent child obesity, by
      modifying the food environment with community-selected foods. Four communities
      were selected by ethnic composition, income level, two on O'ahu and one neighbor
      island. On each island one community was randomly assigned to intervention and
      one to control. The intervention was implemented through food stores in the
      intervention communities. HFH was designed to strengthen the network between
      local food producers, food distributors, storeowners and consumers, to increase
      the availability of healthier less energy dense foods for children in underserved
      rural communities of Hawai'i. The intervention includes phases: healthier
      beverages, snacks, condiments, and family meals. Moderate to high fidelity was
      achieved for educational materials (shelf labels, posters and educational
      displays). The number of educational displays varied by intervention phase and
      community. Posters were found in place 100% of the time. Shelf labels were found
      intact in the correct location. Low to moderate fidelity was achieved for
      distributors, with some products not stocked. In the intervention communities, 6
      8 week phases focused on target foods with 40 food demonstrations. A total of
      1582 food related samples were distributed. A high to moderate dose and reach of
      the overall intervention was achieved in delivery of the cooking demonstrations.
      A high to moderate dose and reach of the intervention was achieved overall;
      fidelity to the intervention protocol was moderate. To improve healthy local food
      availability in stores in rural communities in Hawai'i, agricultural producers
      reported needing additional support to sell and transport product to local
      stores, rather than to centralized distributors.

PMID- 21886294
TI  - Using coalitions to address childhood obesity: the Hawai'i Nutrition and Physical
      Activity Coalition.

PMID- 21886295
TI  - A Report on the development of the Hawai'i Pediatric Weight Management Toolkit.

PMID- 21886296
TI  - Letter to the editor: Childhood obesity.

PMID- 21886297
TI  - Childhood obesity in Hawai'i: the role of the healthcare provider.

PMID- 21886300
TI  - Cesarean scar dehiscence associated with intrauterine balloon tamponade placement
      after a second trimester dilation and evacuation.
AB  - While surgical abortion is a safe procedure, the most common complication is
      excessive bleeding. Methods to conservatively manage hemorrhage are gaining
      popularity. The authors present a case of a Cesarean scar rupture that occurred
      after an intrauterine balloon tamponade was placed to treat postabortion
      bleeding.

PMID- 21886301
TI  - Dual paraneoplastic syndromes: small cell lung carcinoma-related oncogenic
      osteomalacia, and syndrome of inappropriate antidiuretic hormone secretion:
      report of a case and review of the literature.
AB  - Acquired isolated renal phosphate wasting associated with a tumor, known as
      oncogenic osteomalacia or tumor-induced osteomalacia, is a rare paraneoplastic
      syndrome caused by overproduction of fibroblast growth factor 23. Oncogenic
      osteomalacia is usually associated with benign mesenchymal tumors. Syndrome of
      inappropriate antidiuretic hormone secretion (SIADH), on the other hand, is a
      common paraneoplastic syndrome caused by small cell carcinoma (SCC). Concomitant
      oncogenic osteomalacia and SIADH associated with SCC is very rare with only 4
      other cases reported in the literature. The authors report a case of small cell
      lung cancer (SCLC)-related renal wasting hypophosphatemia and concurrent SIADH,
      and review the literature reporting 9 other cases of SCC associated with
      oncogenic osteomalacia. Almost half of reported cases of renal phosphate wasting
      associated with SCC concomitantly presented with SIADH. These cases had initial
      serum phosphorus level lower and survival periods shorter than those without
      SIADH. This rare combination of a dual paraneoplastic syndrome and low serum
      phosphorus may be a poor prognostic sign. In addition, both renal phosphate
      wasting and SIADH usually occur in a short period of time before identification
      of SCC. Therefore, renal wasting hypophosphatemia with concomitant
      SIADH/hyponatremia should prompt a search for SCC rather than a benign
      mesenchymal tumor.

PMID- 21886302
TI  - Koch's postulates, carnivorous cows, and tuberculosis today.
AB  - With Koch's announcement in 1882 of his work with the tubercle bacillus, his
      famous postulates launched the rational world of infectious disease and an abrupt
      social change--strict patient isolation. The postulates, so successful at their
      inception, soon began to show some problems, particularly with cholera, which
      clearly violated some of Koch's requirements. Subsequent studies of other
      diseases and the discovery of entirely new ones have so altered and expanded the
      original postulates that they now are little but a precious touch of history. The
      present additions and replacements of the original concepts are skillful changes
      that several authors have devised to introduce new order into understanding
      complex viral and prion diseases. In 1988, this knowledge, with the totally
      rational response of the British population and its cattle industry, was critical
      in promptly blocking the threatened epidemic of human prion disease. In contrast,
      the recent upsurge of tuberculosis (TB) in the worldwide AIDS epidemic in
      developing countries, and the sudden increase in metabolic syndrome in wealthy
      ones, suggests the need for focused sociobiologic research seeking ways to affect
      the damaging lifestyle behavior of many less educated populations in both
      settings. The world awaits an equivalent of Koch's Postulates in sociobiology to
      explain and possibly avert large self-destructive behaviors.

PMID- 21886303
TI  - Breast cancer worry among women awaiting mammography: is it unfounded? Does prior
      counseling help?
AB  - The purpose of this study was to explore the prevalence of breast cancer anxiety
      and risk counseling in women undergoing mammography, and the association with
      known risk factors for cancer. Women awaiting mammography were surveyed regarding
      anxiety, prior breast cancer risk counseling, demographic and risk factors.
      Anxiety was assessed via 7-point Likert-type scale (LS). Risk was defined by Gail
      model or prior breast cancer. Data were analyzed by nonparametric methods;
      significance determined at alpha = 0.05. Of 227 women surveyed, 54 were
      classified "higher risk". Counseling prevalence was similar (52%) for all ethnic
      groups, but higher (72%, P<0.001) for "higher risk" women. On average, women
      awaiting screening/diagnostic mammography were somewhat worried (median LS = 4).
      Worry was significantly higher (P<0.05) in "higher risk" women (LS = 5), and in
      women living outside Honolulu (LS = 6). Counseling by primary care physicians
      (PCP) did not correlate with lower worry scores. It was concluded that most women
      awaiting mammography are not unduly anxious. Additionally, the findings showed a
      correlation between a woman's concern about developing cancer with known risk
      factors and rural residence.

PMID- 21886304
TI  - Training the next generation of minority health scientists: a STEP-UP in the
      right direction.

PMID- 21886307
TI  - Moyamoya disease in pregnancy: a case series and review of management options.
AB  - BACKGROUND: Pregnancy has a potentially deleterious affect on moyamoya disease
      (MMD), a cerebrovascular condition characterized by spontaneous occlusion of the
      distal internal carotid arteries resulting in the neoangiogenesis of fragile
      collateral blood vessels. The disease renders patients susceptible to both
      hemorrhagic and ischemic stroke. METHODS: A 16-year (1995-2010) chart review was
      performed at the Kapi'olani Medical Center for Women and Children and the Queen's
      Medical Center, the two largest birthing centers in Hawai'i. RESULTS: The authors
      report on three women with MMD who had the revascularization surgery prior to
      their first pregnancy and experienced successful pregnancy outcomes without the
      MMD symptoms. Two of these were managed with antiplatelet agents, one with
      calcium channel blockers, and two with magnesium sulphate in the perioperative
      period. CONCLUSION: The authors' cases demonstrate different medical therapies,
      which may be of benefit for MMD with and without revascularization surgery during
      pregnancy.

PMID- 21886308
TI  - A polymorphism in the retinol binding protein 4 gene is not associated with
      gestational diabetes mellitus in several different ethnic groups.
AB  - OBJECTIVE: Various Asian and Pacifific Islander groups have higher prevalence
      rates of type 2 diabetes and gestational diabetes. This increased incidence is
      likely to include genetic factors. Single nucleotide polymorphisms in the retinol
      binding protein 4 gene have been linked to the occurrence of type 2 diabetes.
      Hypothesizing a link between retinol binding protein 4 and gestational diabetes,
      we performed a candidate gene study to look for an association between an
      important retinol binding protein gene polymorphism (rs3758539) and gestational
      diabetes. STUDY DESIGN: Blood was collected from Caucasian, Asian, and Pacific
      Islander women diagnosed with gestational diabetes and from ethnically matched
      non-diabetic controls. DNA was extracted and real time PCR technology (TaqMan,
      Applied Biosystems) used to screen for the rs3758539 single nucleotide
      polymorphism located 5' of exon 1 of the retinol binding protein 4 gene. RESULTS:
      Genotype and allele frequencies in the controls and gestational diabetes cases
      were tested using chi-square contingency tests. Genotype frequencies were in
      Hardy-Weinberg equilibrium. There was no association between the rs3758539
      retinol binding protein 4 single nucleotide polymorphism and gestational diabetes
      in the Caucasian, Filipino, or Pacific Islander groups. CONCLUSION:
      Interestingly, the rs3758539 retinol binding protein 4 single nucleotide
      polymorphism was not found to be associated with gestational diabetes. The
      absence of association suggests that gestational and type 2 diabetes may have
      more divergent molecular pathophysiology than previously suspected.

PMID- 21886309
TI  - The challenges of collecting data on race and ethnicity in a diverse, multiethnic
      state.
AB  - Race and ethnicity are commonly used predictor variables in medical and public
      health research. Including these variables has helped researchers to describe the
      etiology of certain disease states. Including race and ethnicity in research has
      been hypothesis generating in terms of the relationship between genetic and
      environmental factors in the development of disease. Eliminating health
      disparities among different racial and ethnic groups has become a national
      priority. However, incorporating race and ethnicity into health research is
      complex because these variables are difficult to define and individuals often
      identify with more than one race or ethnicity. As a "minority-majority",
      multiethnic, multiracial state, Hawai'i faces unique challenges in incorporating
      race and ethnicity into research. As the demographics of the United States
      continue to evolve, many of the challenges faced in Hawai'i will apply to the
      United States as a whole.

PMID- 21886311
TI  - Medical school hotline: first and lasting impressions of the John A. Burns school
      of medicine.

PMID- 21886310
TI  - Student-written simulation scenarios: a novel cognitive assessment method in a
      trauma curriculum.
AB  - INTRODUCTION: Global cognitive and psychomotor assessment in simulation based
      curricula is complex. We describe assessment of novices' cognitive skills in a
      trauma curriculum using a simulation aligned facilitated discovery method.
      METHODS: Third-year medical students in a surgery clerkship completed two student
      written simulation scenarios (SWSS) as an assessment method in a trauma
      curriculum employing high fidelity human patient simulators (manikins). SWSS
      consisted of written physiologic parameters, intervention responses, a
      performance evaluation form, and a critical interventions checklist. RESULTS:
      Seventy-one students participated. SWSS scores were compared to multiple choice
      test (MCQ), checklist-graded solo performance in a trauma scenario (STS), and
      clerkship summative evaluation grades. The SWSS appeared to be slightly better
      than STS in discriminating between Honors and non-Honors students, although the
      mean scores of Honors and non-Honors students on SWSS, STS, or MCQ were not
      significantly different. SWSS exhibited good equivalent form reliability
      (r=0.88), and higher interrater reliability versus STS (r=0.93 vs r=0.79).
      CONCLUSION: SWSS is a promising assessment method for simulation based curricula.

PMID- 21886319
TI  - A message from the editor.

PMID- 21886320
TI  - Public health in action: give mothers support for breastfeeding.

PMID- 21886322
TI  - National trends in occupational injuries before and after 1992 and predictors of
      workers' compensation costs.
AB  - OBJECTIVE: Numbers and costs of occupational injuries and illnesses are
      significant in terms of morbidity and dollars, yet our understanding of time
      trends is minimal. We investigated trends and addressed some common hypotheses
      regarding causes of fluctuations. METHODS: We pulled data on incidence rates (per
      100 full-time employed workers) for injuries and illnesses from the U.S. Bureau
      of Labor Statistics and on costs and benefits from the National Academy of Social
      Insurance for 1973 through 2007. Rates reflected all injury and illness cases,
      lost work-time cases, and cases resulting in at least 31 days away from work. We
      adjusted dollar costs (premiums) and benefits for inflation and measured them per
      employed worker. We plotted data in time-trend charts and ran linear regressions.
      RESULTS: From 1973 to 1991, there was a weak to nonexistent downward trend for
      injury and illness rates, and rates were strongly and negatively correlated with
      the unemployment rate. From 1992 to 2007, there were strong, consistent downward
      trends, but no longer were there statistically significant correlations with
      unemployment. Significant predictors (and signs) of workers' compensation
      premiums for 1973-2007 included medical price inflation (positive), number of
      lost-time injuries (positive), the Dow Jones Industrial Average (negative), and
      inflation-adjusted interest rate on U.S. Treasury bonds (negative). Dollars of
      benefits were positively and significantly predicted by medical inflation and
      number of lost-time cases. For 1992-2007, the Dow Jones variable was the only
      robust predictor of premiums; the number of injuries was not a significant
      positive predictor. CONCLUSION: We had two major conclusions. First, the year
      1992 marked a sharp contrast in trends and correlations between unemployment and
      incidence rates for occupational injuries and illnesses. Second, for the entire
      time period (1973-2007), insurance carriers' premiums were strongly associated
      with returns on investments.

PMID- 21886323
TI  - Recruitment-adjusted estimates of HIV prevalence and risk among men who have sex
      with men: effects of weighting venue-based sampling data.
AB  - OBJECTIVES: We investigated the impact of recruitment bias within the venue-based
      sampling (VBS) method, which is widely used to estimate disease prevalence and
      risk factors among groups, such as men who have sex with men (MSM), that
      congregate at social venues. METHODS: In a 2008 VBS study of 479 MSM in New York
      City, we calculated venue-specific approach rates (MSM approached/MSM counted)
      and response rates (MSM interviewed/MSM approached), and then compared crude
      estimates of HIV risk factors and seroprevalence with estimates weighted to
      address the lower selection probabilities of MSM who attend social venues
      infrequently or were recruited at high-volume venues. RESULTS: Our approach rates
      were lowest at dance clubs, gay pride events, and public sex strolls, where venue
      volumes were highest; response rates ranged from 39% at gay pride events to 95%
      at community-based organizations. Sixty-seven percent of respondents attended MSM
      oriented social venues at least weekly, and 21% attended such events once a month
      or less often in the past year. In estimates adjusted for these variations, the
      prevalence of several past-year risk factors (e.g., unprotected anal intercourse
      with casual/exchange partners, >=5 total partners, group sex encounters, at least
      weekly binge drinking, and hard-drug use) was significantly lower compared with
      crude estimates. Adjusted HIV prevalence was lower than unadjusted prevalence
      (15% vs. 18%), but not significantly. CONCLUSIONS: Not adjusting VBS data for
      recruitment biases could overestimate HIV risk and prevalence when the selection
      probability is greater for higher-risk MSM. While further examination of
      recruitment-adjustment methods for VBS data is needed, presentation of both
      unadjusted and adjusted estimates is currently indicated.

PMID- 21886324
TI  - Barriers to routine HIV testing among Massachusetts community health center
      personnel.
AB  - OBJECTIVES: We assessed the extent to which Centers for Disease Control and
      Prevention (CDC) recommendations have influenced routine HIV testing among
      Massachusetts community health center (CHC) personnel, and identified specific
      barriers and facilitators to routine testing. METHODS: Thirty-one CHCs were
      enrolled in the study. We compared those that did and did not receive funding
      support from the federal Ryan White HIV/AIDS Program. An anonymous survey was
      administered to a maximum five personnel from each CHC, including a senior
      administrator, the medical director, and three medical providers. Overall, 137
      participants completed the survey. RESULTS: Among all CHCs, 53% of administrators
      reported having implemented routine HIV testing at their CHCs; however, only 33%
      of medical directors/providers reported having implemented routine HIV testing in
      their practices (p<0.05). Among administrators, 60% of those from Ryan White
      supported CHCs indicated that both they and their CHCs were aware of CDC's
      recommendations, compared with 27% of administrators from non-Ryan White
      supported CHCs. The five most frequently reported barriers to the implementation
      of routine HIV testing were (1) constraints on providers' time (68%), (2) time
      required to administer counseling (65%), (3) time required to administer informed
      consent (52%), (4) lack of funding (35%), and (5) need for additional training
      (34%). In a multivariable logistic regression model, the provision of on-site HIV
      testing by nonmedical staff resulted in increased odds of conducting routine HIV
      testing (odds ratio [OR] = 9.84, 95% confidence interval [CI] 1.77, 54.70).
      However, the amount of time needed to administer informed consent was associated
      with decreased odds of providing routine testing (OR=0.21, 95% CI 0.05, 0.92).
      CONCLUSIONS: Routine HIV testing is not currently being implemented uniformly
      among Massachusetts CHCs. Future efforts to increase implementation should
      address personnel concerns regarding time and staff availability.

PMID- 21886325
TI  - HIV/AIDS knowledge scores and perceptions of risk among African American students
      attending historically black colleges and universities.
AB  - OBJECTIVE: African American young adults are disproportionately affected by the
      HIV/AIDS epidemic and often unaware of their personal risk for HIV. Historically
      black colleges and universities (HBCUs) enroll 25% of college-educated African
      American young adults and can play an important role in HIV prevention. We
      examined HIV/AIDS knowledge of students at HBCUs to inform and strengthen our HIV
      prevention efforts at HBCUs. METHODS: African American undergraduate HBCU
      students completed online surveys assessing HIV/AIDS knowledge and behaviors, and
      we analyzed data to assess their knowledge and behaviors. RESULTS: A total of
      1,051 of 1,230 surveys completed (85.4%) were analyzable. Eighty-two percent of
      students had average/high HIV knowledge scores. Seventy-nine percent of students
      surveyed perceived themselves to be at low risk for HIV infection; 64% of those
      who had at least two or more sex partners had not used a condom at last sex
      encounter. In the final model, significant independent effects were identified
      for average/high knowledge of HIV risk, including agreeing with assessing a
      potential partner's HIV risk by all of the five actions listed (adjusted odds
      ratio [AOR] = 2.7, 95% confidence interval [CI] 1.7, 4.3) and never using a
      needle to inject drugs (AOR=5.6, 95% CI 3.2, 9.7). CONCLUSIONS: Educating
      students about effectively assessing sex partner risk will improve HIV knowledge
      and prevention efforts at HBCUs.

PMID- 21886326
TI  - Rates of hospital visits for assault during pregnancy and the year postpartum:
      timing matters.
AB  - OBJECTIVE: To clarify the risk of violence for women during pregnancy and the
      first year postpartum, we examined the timing of hospital visits for assault
      among a population cohort of women in Massachusetts. METHODS: Using linked
      natality and hospital data from 2001 through 2007 for Massachusetts, we examined
      the timing of hospital (i.e., emergency, inpatient, and observation) visits for
      maternal assault during seven time periods: the three prenatal trimesters and
      four three-month postpartum periods. To describe the risk of assault for each of
      the time periods, we calculated the rate as the number of such visits per 100,000
      person-weeks. We used the denominator of 100,000 person-weeks to adjust for
      variable lengths of gestation and for postpartum periods shortened by subsequent
      pregnancies. RESULTS: Rates of hospital visits for maternal assault were highest
      in the first trimester and lowest in the third trimester, with rates of 16.0 and
      5.8 per 100,000 person-weeks, respectively. The four postpartum period rates were
      higher than the third trimester rate but never reached the levels observed in the
      first and second trimesters. CONCLUSIONS: These findings suggest a changing rate
      for assault visits during each prenatal trimester and postpartum period. In
      addition, the importance of violence prevention strategies as part of women's
      health care across the life span and the need for preconception care initiatives
      are reaffirmed.

PMID- 21886327
TI  - Smoke-free laws in bars and restaurants: does support among teens and young
      adults change after a statewide smoke-free law?
AB  - OBJECTIVE: We assessed changes in levels of support for smoke-free bars and
      restaurants among teens and young adults before and after implementation of a
      statewide smoke-free law. METHODS: We measured support for smoke-free bars and
      restaurants among teens and young adults aged 16-24 years living in Minnesota
      (n=2,785) and five comparison states (n=404), up to 12 months before and up to
      six months after Minnesota's smoke-free law went into effect in October 2007. We
      compared changes in support among three subgroups-Minnesota participants who
      lived with a previous local smoke-free law, Minnesota participants who did not
      live with a previous local smoke-free law, and participants from the comparison
      states-before and after Minnesota's statewide smoke-free law went into effect.
      RESULTS: Support for smoke-free restaurants and bars among participants in
      Minnesota and comparison states increased after Minnesota's smoke-free law went
      into effect. Minnesotans, both those living with and without a previous local
      smoke-free law, showed similar increases in support for smoke-free restaurants as
      participants in comparison states. However, Minnesotans living without a previous
      local law showed larger increases in support for smoke-free bars than both those
      in comparison states and those living in Minnesota with a previous local smoke
      free law. CONCLUSIONS: Our study employed a more robust design than similar
      studies and focused on the teen and young adult population. Our results will help
      advocates and policy makers demonstrate how public support for smoke-free laws
      increases following smoke-free legislation, particularly among those who were not
      previously living with a local smoke-free law.

PMID- 21886328
TI  - Tuberculosis in indigenous peoples in the U.S., 2003-2008.
AB  - OBJECTIVES: We examined trends and epidemiology of tuberculosis (TB) across
      racial/ethnic groups to better understand TB disparities in the United States,
      with particular focus on American Indians/Alaska Natives (AI/ANs) and Native
      Hawaiians/other Pacific Islanders (NH/PIs). METHODS: We analyzed cases in the
      U.S. National Tuberculosis Surveillance System and calculated TB case rates among
      all racial/ethnic groups from 2003 to 2008. Socioeconomic and health indicators
      for counties in which TB cases were reported came from the Health Resources and
      Services Administration Area Resource File. RESULTS: Among the 82,836 TB cases,
      914 (1.1%) were in AI/ANs and 362 (0.4%) were in NH/PIs. In 2008, TB case rates
      for AI/ANs and NH/PIs were 5.9 and 14.7 per 100,000 population, respectively,
      rates that were more than five and 13 times greater than for non-Hispanic white
      people (1.1 per 100,000 population). From 2003 to 2008, AI/ANs had the largest
      percentage decline in TB case rates (-27.4%) for any racial/ethnic group, but
      NH/PIs had the smallest percentage decline (-3.5%). AI/ANs were more likely than
      other racial/ethnic groups to be homeless, excessively use alcohol, receive
      totally directly observed therapy, and come from counties with a greater
      proportion of people living in poverty and without health insurance. A greater
      proportion of NH/PIs had extrapulmonary disease and came from counties with a
      higher proportion of people with a high school diploma. CONCLUSIONS: There is a
      need to develop flexible TB-control strategies that address the social
      determinants of health and that are tailored to the specific needs of AI/ANs and
      NH/PIs in the U.S.

PMID- 21886329
TI  - The persistent gap in health-care coverage between low- and high-income workers
      in Washington State: BRFSS, 2003-2007.
AB  - OBJECTIVES: We examined the disparities in health-care coverage between low- and
      high-income workers in Washington State (WA) to provide support for possible
      policy decisions for uninsured workers. METHODS: We examined data from the WA
      Behavioral Risk Factor Surveillance System 2003-2007 and compared workers aged 18
      64 years of low income (annual household income <$35,000) and high income (annual
      household income >=$35,000) on proportions and sources of health-care coverage.
      We conducted multivariable logistic regression analyses on factors that were
      associated with the uninsured. RESULTS: Of the 54,536 survey respondents who were
      working-age adults in WA, 13,922 (25.5%) were low-income workers. The proportions
      of uninsured were 38.2% for low-income workers and 6.3% for high-income workers.
      While employment-based health benefits remained a dominant source of health
      insurance coverage, they covered only 40.2% of low-income workers relative to
      81.5% of high-income workers. Besides income, workers were more likely to be
      uninsured if they were younger; male; Hispanic; less educated; not married;
      current smokers; self-employed; or employed in agriculture/forestry/fisheries,
      construction, and retail. More low-income workers (28.7%) reported cost as an
      issue in paying for health services than did their high-income counterparts
      (6.7%). CONCLUSION: A persistent gap in health-care coverage exists between low-
      and high-income workers. The identified characteristics of these workers can be
      used to implement policies to expand health insurance coverage.

PMID- 21886330
TI  - Disparities in the prevalence of obesity in Boston: results from the Boston Area
      Community Health (BACH) survey.
AB  - OBJECTIVE: This study examined disparities in the prevalence of obesity to
      determine how future prevention and/or intervention efforts should be developed
      to remedy obesity. METHODS: We obtained individual information of
      sociodemographic characteristics, comorbid conditions, and lifestyle behaviors
      from the Boston Area Community Health (BACH) survey for 2002-2005. To account for
      the complex BACH sampling design, observations were weighted inversely to their
      probability of selection, and sampling weights were poststratified to the Boston
      population from the U.S. Census 2000. We tested all possible two- and three-way
      interaction terms from a multivariate logistic regression model. RESULTS: After
      controlling for individual determinants in detail and focusing on the population
      within a single city, the associations of sociodemographic characteristics,
      comorbid conditions, and lifestyle behaviors with obesity were consistent with
      previous findings. Notably, three two-way interaction terms were significantly
      associated with obesity: (1) race/ethnicity and gender, (2) gender and other
      people in the household, and (3) race/ethnicity and alcohol consumption.
      CONCLUSIONS: Future obesity prevention and/or intervention programs in Boston
      need to be primarily gender- and racially/ethnically specific to minimize cost
      and maximize results. Additional considerations are needed to take into account
      the differences in age, the presence of other people in the household, and
      education level.

PMID- 21886331
TI  - Predictive modeling the physician assistant supply: 2010-2025.
AB  - OBJECTIVE: A component of health-care reform in 2010 identified physician
      assistants (PAs) as needed to help mitigate the expected doctor shortage. We
      modeled their number to predict rational estimates for workforce planners.
      METHODS: The number of PAs in active clinical practice in 2010 formed the
      baseline. We used graduation rates and program expansion to project annual
      growth; attrition estimates offset these amounts. A simulation model incorporated
      historical trends, current supply, and graduation amounts. Sensitivity analyses
      were conducted to systematically adjust parameters in the model to determine the
      effects of such changes. RESULTS: As of 2010, there were 74,476 PAs in the active
      workforce. The mean age was 42 years and 65% were female. There were 154
      accredited educational programs; 99% had a graduating class and produced an
      average of 44 graduates annually (total n=6,776). With a 7% increase in graduate
      entry rate and a 5% annual attrition rate, the supply of clinically active PAs
      will grow to 93,099 in 2015, 111,004 in 2020, and 127,821 in 2025. This model
      holds clinically active PAs in primary care at 34%. CONCLUSIONS: The number of
      clinically active PAs is projected to increase by almost 72% in 15 years.
      Attrition rates, especially retirement patterns, are not well understood for PAs,
      and variation could affect future supply. While the majority of PAs are in the
      medical specialties and subspecialties fields, new policy steps funding PA
      education and promoting primary care may add more PAs in primary care than the
      model predicts.

PMID- 21886332
TI  - Changes in the relationship between marriage and preterm birth, 1989-2006.
AB  - OBJECTIVE: Maternal marriage has historically been protective against preterm
      birth (PTB); however, social norms and behaviors surrounding marriage have
      changed over time in the United States. We analyzed secular trends in the
      relationship between marriage and PTB. METHODS: We collected data about all
      births in Michigan between 1989 and 2006 to assess (1) the relationship between
      marital status and PTB and moderately PTB risk by year, and (2) the relationship
      between married and unmarried status and PTB and moderately PTB by year relative
      to similar marital status in 1989. RESULTS: Among nearly 2.4 million births
      between 1989 and 2006, PTB risk among married mothers increased while risk among
      unmarried mothers decreased. In adjusted models, married status became less
      protective against PTB relative to unmarried status over time by year, and was
      associated with higher risk of PTB over time. Moderately PTB risk increased among
      both married and unmarried groups, but more so among married mothers. CONCLUSION:
      Our findings suggest that marriage is becoming less protective against PTB over
      time. The influence of social factors on risk for adverse birth outcomes is
      likely dynamic, suggesting that ongoing revisions to our understanding are in
      order.

PMID- 21886333
TI  - Outbreak of tuberculosis among Guatemalan immigrants in rural Minnesota, 2008.
AB  - OBJECTIVES: We described the outbreak investigation and control measures after
      the Minnesota Department of Health identified a cluster of tuberculosis (TB)
      cases among Guatemalan immigrants within three rural Minnesota counties in August
      2008. METHODS: TB cases were diagnosed by tuberculin skin test followed by chest
      radiography and sputum testing for Mycobacterium tuberculosis (M. tuberculosis).
      We reviewed medical records, interviewed patients, and completed a contact
      investigation for each infectious case. We used isolate genotyping to confirm
      epidemiologic links between cases. RESULTS: The index case was a six-month-old
      U.S.-born male with Guatemalan parents. Although he experienced four months of
      cough and fever, TB was not considered at two medical visits but was diagnosed
      upon hospitalization in May 2008. The presumed source of infection was a
      Guatemalan male aged 25 years who sang in a band that practiced in the infant's
      house and whose pulmonary TB was diagnosed at hospitalization in June 2008,
      despite his having sought medical attention for symptoms seven months earlier.
      Among the 16 identified TB cases, 14 were outbreak-related. Three genetically
      distinct M. tuberculosis strains circulated. Of 150 contacts of the singer, 62
      (41%) had latent TB infection and 13 (9%), including 10 children, had TB disease.
      CONCLUSIONS: In this outbreak, delayed diagnoses contributed to M. tuberculosis
      transmission. Isolate genotyping corroborated the social links between outbreak
      related patients. More timely diagnosis of TB among immigrants and their children
      can prevent TB transmission among communities in rural, low-incidence areas that
      might have limited resources for contact investigations.

PMID- 21886334
TI  - Methods of generating state revenue for breast cancer prevention and early
      detection: an analysis of pink dollars.
AB  - OBJECTIVE: We assessed income tax check-offs, specialty license plates, and
      lottery tickets as ways states raise funds for the early detection and prevention
      of breast cancer. METHODS: We conducted an inventory of state legislation
      allowing these revenue-generating methods, and collected and compared information
      on each initiative. We conducted logistic regression analyses to compare these
      methods with state breast cancer mortality rates. RESULTS: Eighteen states had
      programs for contributions through an income tax check-off. Revenue for tax check
      offs and plates is influenced by state population. The median annual revenue for
      the income tax check-off was $115,000. Twenty-six states had breast cancer
      license plates generating more than $4.1 million in revenue. The extra cost of
      the plates ranged from $20 to 75 (mean = $37). Only Illinois offered a state
      breast cancer lottery ticket, which raised $4 million from 2005 to 2009. States
      with medium or high breast cancer mortality rates were 2.5 times more likely to
      offer breast cancer specialty license plates than states with low breast cancer
      mortality rates; however, we found no statistically significant difference in
      breast cancer mortality tertiles by income tax check-off. CONCLUSION: Revenue
      generating breast cancer initiatives can be successful strategies for states to
      raise funds for breast cancer prevention and early detection programs. Although
      these initiatives can generate revenue, amounts are variable due to population
      differences, the number of other plates/check-offs/lotteries offered, and the
      choice to decrease donations during difficult economic times. State breast cancer
      mortality rates may influence the availability of these initiatives.

PMID- 21886335
TI  - Using GIS-based density maps of HIV surveillance data to identify previously
      unrecognized geographic foci of HIV burden in an urban epidemic.

PMID- 21886337
TI  - The U.S. Constitution's Commerce Clause, the Supreme Court, and public health.

PMID- 21886340
TI  - A method to enhance public health faculty participation in health policy
      formation.

PMID- 21886341
TI  - Sustainability of solar disinfection to provide safe drinking water in rural
      Peru.

PMID- 21886342
TI  - Frequency-dependent electrodeformation of giant phospholipid vesicles in AC
      electric field.
AB  - A model of vesicle electrodeformation is described which obtains a parametrized
      vesicle shape by minimizing the sum of the membrane bending energy and the energy
      due to the electric field. Both the vesicle membrane and the aqueous media inside
      and outside the vesicle are treated as leaky dielectrics, and the vesicle itself
      is modeled as a nearly spherical shape enclosed within a thin membrane. It is
      demonstrated (a) that the model achieves a good quantitative agreement with the
      experimentally determined prolate-to-oblate transition frequencies in the
      kilohertz range and (b) that the model can explain a phase diagram of shapes of
      giant phospholipid vesicles with respect to two parameters: the frequency of the
      applied alternating current electric field and the ratio of the electrical
      conductivities of the aqueous media inside and outside the vesicle, explored in a
      recent paper (S. Aranda et al., Biophys J 95:L19-L21, 2008). A possible use of
      the frequency-dependent shape transitions of phospholipid vesicles in
      conductometry of microliter samples is discussed.

PMID- 21886343
TI  - Mechanical behaviour analyses of sap ascent in vascular plants.
AB  - A pure mechanical anisotropic model of a tree trunk has been developed based on
      the 3D finite element method. It simulates the microscopic structure of vessels
      in the trunk of a European beech (Fagus sylvatica) in order to study and analyse
      its mechanical behaviour with different configurations of pressures in the
      conduits of xylem and phloem. The dependence of the strains at the inner bark was
      studied when sap pressure changed. The comparison with previously published
      experimental data leads to the conclusion that a great tensile stress-or
      'negative pressure'-must exist in the water column in order to achieve the
      measured strains if only the mechanical point of view is taken into account.
      Moreover, the model can help to design experiments where qualitatively knowing
      the strains and the purely mechanical behaviour of the tree is required.

PMID- 21886344
TI  - Characterization of excitation beam on second-harmonic generation in fibrillous
      type I collagen.
AB  - Following our established theoretical model to deal with the second-harmonic
      generation (SHG) excited by a linearly polarized focused beam in type I collagen,
      in this paper, we further quantitatively characterize the differences between SHG
      emissions in type I collagen excited by collimated and focused beams. The effects
      of the linear polarization angle (alpha) and the fibril polarity characterized by
      the hyperpolarizability ratio rho on SHG emission has been compared under
      collimated and focused beam excitation, respectively. In particular, SHG emission
      components along the i axis [Formula: see text] (i = x,y,z), the induced SHG
      emission deviation angle gamma(ij), and the detected SHG signals (I(2omega,ij))
      in the ij plane by rotating the applied polarizer angle phi(ij) have been
      investigated (i = x, x, y; j = y, z, z). Results show that under our simulation
      model, SHG emission in the xy plane, such as I(2omega,x) ,I(2omega,y) ,gamma(xy)
      and I(2omega,xy) varying as polarization angle (alpha) under collimated and
      focused light, presents no significant difference. The reverse of the fibril
      polarity has induced great impact on I(2omega,x) ,gamma(xy) and I(2omega,xy) in
      both collimated and focused light. I(2omega,x) and gamma(xy) show similarity, but
      I(2omega,xy) at alpha = 30 degrees  demonstrates a slight difference in focused
      light to that in collimated light. Under focused light, the reverse of fibril
      polarity causes obvious changes of the collected SHG intensity I(2omega,xz) and
      I(2omega,yz) at a special polarization angle alpha = 60 degrees  and gamma(xz),
      gamma(yz) along alpha.

PMID- 21886346
TI  - FTIR spectroscopy of synthesized racemic nonacosan-10-ol: a model compound for
      plant epicuticular waxes.
AB  - As there are no published graphically presented, detailed IR spectra of nonacosan
      10-ol (occurring naturally and widely in plant epicuticular waxes of nanotube
      form), near IR FTIR spectroscopy (fundamentals, overtones and combinations) has
      been performed on laboratory synthesized racemic nonacosan-10-ol, as a
      crystalline solid on Mylar and polypropylene substrates. Room temperature, in
      vacuo data are presented graphically, in full, and show evidence of extensive
      hydrogen bonding, an orthorhombic perpendicular subcell, a methylene wagging
      progression, diagnostic of all-trans conformational order, and Fermi resonance.
      Moderate or stronger anharmonicity is confirmed. Detailed discussion,
      quantitative in parts, is given of the observed spectral features, especially as
      to how they inform crystal structure and molecular conformation, and assignments
      given for some of the features. The results will serve as a reference for future
      IR studies of the natural epicuticular wax nanotube form of (S)-nonacosan-10-ol.

PMID- 21886345
TI  - Modeling organelle transport in branching dendrites with a variable cross
      sectional area.
AB  - The purpose of this paper is to develop a method for calculating organelle
      transport in dendrites with a non-uniform cross-sectional area that depends on
      the distance from the neuron soma. The model is based on modified Smith-Simmons
      equations governing molecular motor-assisted organelle transport. The developed
      method is then applied to simulating organelle transport in branching dendrites
      with two particular microtubule (MT) orientations reported from experiments. It
      is found that the rate of organelle transport toward a dendrite's growth cone
      heavily depends on the MT orientation, and since there is experimental evidence
      that the MT orientation in a particular region of a dendrite may depend on the
      dendrite's developmental stage, the obtained results suggest that a rearrangement
      of the MT structure may depend on the amount of organelles needed at the growth
      cone.

PMID- 21886347
TI  - Prediction of bending stiffness and deformed shape of non-axially compressed
      microtubule by a semi-analytical approach.
AB  - The bending stiffness of a microtubule is one of the most important parameters
      needed in the analysis of microtubule deformation. In this study, a semi
      analytical approach is developed to predict the bending stiffness and deformed
      shape of a non-axially compressed microtubule in an explicit closed form. By
      using the solution presented in this paper and the experimentally observed values
      given in the literature, both the deformed configuration and bending stiffness of
      a single microtubule are determined. The proposed method is validated by
      comparing the obtained results with available data in the literature. The
      comparison shows that the present semi-analytical formulation provides the same
      accuracy with reduced numerical effort.

PMID- 21886348
TI  - Dedications honor sleep research and sleep medicine trailblazer Dr. William C.
      Dement.

PMID- 21886349
TI  - Insomnia is a risk factor for suicide-what are the next steps?

PMID- 21886350
TI  - The economic burden of insomnia at the workplace. An opportunity and time for
      intervention?

PMID- 21886351
TI  - Sleep duration and childhood obesity: moving from research to practice.

PMID- 21886352
TI  - Sleeping problems and suicide in 75,000 Norwegian adults: a 20 year follow-up of
      the HUNT I study.
AB  - OBJECTIVES: To investigate the association of sleeping problems with suicide
      risk. DESIGN: Prospective cohort study linking health survey information on sleep
      problems to Norway's national mortality registry. Participants were followed up
      from 1984-6 until December 31, 2004. SETTING: Residents of Nord-Trondelag County,
      Norway, aged 20 years or older in 1984-6. PARTICIPANTS: Altogether 87,285 people
      were eligible for the survey and 74,977 (86%) took part in one or more aspects of
      the study. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Three percent of
      participants experienced sleeping problems every night, 5% experienced problems
      "often" and 31% reported problems "sometimes." There were 188 suicides during
      follow-up. Sleeping problems at baseline were strongly associated with subsequent
      suicide risk. Compared to participants who reported no sleeping problems the age-
      and sex- adjusted hazard ratios for suicide were 1.9 (CI 1.3-2.6), 2.7 (CI 1.4
      5.0), and 4.3 (CI 2.3-8.3) for reporting sleeping problems sometimes, often, or
      almost every night, respectively. Associations were stronger in younger (< 50
      years) participants, but we found no statistical evidence for gender differences.
      Adjusting for measures of common mental disorder and alcohol use at baseline
      weakened the associations, but the 3% of subjects with the worst sleep patterns
      remained at two fold increased risk of suicide. CONCLUSIONS: Sleeping problems
      are a marker of suicide risk, mainly due to the presence of both sleeping
      problems and mixed anxiety and depression. Physicians should be aware of the
      possible vulnerability for people affected by sleeping problems.

PMID- 21886353
TI  - Insomnia and the performance of US workers: results from the America insomnia
      survey.
AB  - STUDY OBJECTIVES: To estimate the prevalence and associations of broadly defined
      (i.e., meeting full ICD-10, DSM-IV, or RDC/ICSD-2 inclusion criteria) insomnia
      with work performance net of comorbid conditions in the America Insomnia Survey
      (AIS). DESIGN/SETTING: Cross-sectional telephone survey. PARTICIPANTS: National
      sample of 7,428 employed health plan subscribers (ages 18+). INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Broadly defined insomnia was assessed with the Brief
      Insomnia Questionnaire (BIQ). Work absenteeism and presenteeism (low on-the-job
      work performance defined in the metric of lost workday equivalents) were assessed
      with the WHO Health and Work Performance Questionnaire (HPQ). Regression analysis
      examined associations between insomnia and HPQ scores controlling 26 comorbid
      conditions based on self-report and medical/pharmacy claims records. The
      estimated prevalence of insomnia was 23.2%. Insomnia was significantly associated
      with lost work performance due to presenteeism (chi2 (1) = 39.5, P < 0.001) but
      not absenteeism (chi2 (1) = 3.2, P = 0.07), with an annualized individual-level
      association of insomnia with presenteeism equivalent to 11.3 days of lost work
      performance. This estimate decreased to 7.8 days when controls were introduced
      for comorbid conditions. The individual-level human capital value of this net
      estimate was $2,280. If we provisionally assume these estimates generalize to the
      total US workforce, they are equivalent to annualized population-level estimates
      of 252.7 days and $63.2 billion. CONCLUSIONS: Insomnia is associated with
      substantial workplace costs. Although experimental studies suggest some of these
      costs could be recovered with insomnia disease management programs, effectiveness
      trials are needed to obtain precise estimates of return-on-investment of such
      interventions from the employer perspective.

PMID- 21886354
TI  - Sleep duration and self-rated health: the national health interview survey 2008.
AB  - BACKGROUND: Self-rated health (SRH) has been shown to consistently predict
      overall mortality and cardiovascular mortality in several population-based
      studies across the world. Similarly sleep duration have been found to be
      associated with cardiovascular disease (CVD) and mortality. However, relatively
      few studies have examined the association between sleep duration and SRH, and the
      results have not been consistent. METHODS: We conducted a cross-sectional study
      of n = 20,663 National Health Interview Survey 2008 participants >= 18 years of
      age (56.2% women). Sleep duration was categorized as <= 5 h, 6 h, 7 h, 8 h, and
      >= 9 h. The main outcome interest was fair/poor SRH (n = 3043). RESULTS: We found
      both short and long sleep duration to be independently associated with fair/poor
      SRH, independent of age, sex, race-ethnicity, smoking, alcohol intake, body mass
      index, physical activity, depression, diabetes mellitus, hypertension, and CVD.
      Compared with a sleep duration of 7 h (referent), the multivariate odds ratio
      (95% confidence interval) of fair/poor SRH was 2.29 (1.86-2.83), 1.68 (1.42
      2.00), 1.38 (1.18-1.61), and 1.98 (1.63-2.40) for sleep duration <= 5, 6, 8, and
      >= 9 h. This association persisted in subgroup analyses by gender, race
      ethnicity, and body mass index categories. CONCLUSION: Compared with sleep
      duration of 7 h, there was a positive association between both shorter and longer
      sleep duration and fair/poor self-rated health in a representative sample of US
      adults.

PMID- 21886355
TI  - Sleep reactivity and insomnia: genetic and environmental influences.
AB  - STUDY OBJECTIVES: Determine the genetic and environmental contributions to sleep
      reactivity and insomnia. DESIGN: Population-based twin cohort. PARTICIPANTS: 1782
      individual twins (988 monozygotic or MZ; 1,086 dizygotic or DZ), including 744
      complete twin pairs (377 MZ and 367 DZ). Mean age was 22.5 +/- 2.8 years; gender
      distribution was 59% women. MEASUREMENTS: Sleep reactivity was measured using the
      Ford Insomnia Response to Stress Test (FIRST). The criterion for insomnia was
      having difficulty falling asleep, staying asleep, or nonrefreshing sleep "usually
      or always" for >= 1 month, with at least "somewhat" interference with daily
      functioning. RESULTS: The prevalence of insomnia was 21%. Heritability estimates
      for sleep reactivity were 29% for females and 43% for males. The environmental
      variance for sleep reactivity was greater for females and entirely due to
      nonshared effects. Insomnia was 43% to 55% heritable for males and females,
      respectively; the sex difference was not significant. The genetic variances in
      insomnia and FIRST scores were correlated (r = 0.54 in females, r = 0.64 in
      males), as were the environmental variances (r = 0.32 in females, r = 0.37 in
      males). In terms of individual insomnia symptoms, difficulty staying asleep (25%
      to 35%) and nonrefreshing sleep (34% to 35%) showed relatively more genetic
      influences than difficulty falling asleep (0%). CONCLUSIONS: Sleep reactivity to
      stress has a substantial genetic component, as well as an environmental
      component. The finding that FIRST scores and insomnia symptoms share genetic
      influences is consistent with the hypothesis that sleep reactivity may be a
      genetic vulnerability for developing insomnia.

PMID- 21886356
TI  - Prevalence and impact of short sleep duration in redeployed OIF soldiers.
AB  - STUDY OBJECTIVES: Short sleep duration (SSD) is common among deployed soldiers.
      The prevalence of SSD during redeployment, however, is unknown. DESIGN: Cross
      sectional study of a brigade combat team (n = 3152 US Army soldiers) surveyed 90
      180 days after completing a 6-15 month deployment to Iraq as part of Operation
      Iraqi Freedom (OIF). Survey items targeted sleep habits and comorbid medical
      conditions. Multivariate logistic regression analyses were performed to calculate
      adjusted odds ratios of medical comorbidities associated with SSD. SETTING: US
      Army Infantry Post. SUBJECTS: All soldiers from a redeploying brigade combat team
      participated in a health assessment between 90 and 180 days upon return to Ft.
      Lewis from Iraq. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: A total of 2738
      (86.9%) soldiers answered questions regarding self-perceived sleep and were
      included in the analysis. Mean sleep duration was 5.8 +/- 1.2 hours. Nineteen
      hundred fifty-nine (72%) slept <= 6 h, but only 16% reported a daytime nap or
      felt their job performance was affected due to lack of sleep. Short sleep was
      more common among soldiers who reported combat exposure. After controlling for
      combat exposure, short sleep duration (SSD) was associated with symptoms of
      depression, posttraumatic stress disorder, panic syndrome, and with high-risk
      health behaviors such as abuse of tobacco and alcohol products, and suicide
      attempts. CONCLUSIONS: SSD is common among redeployed soldiers. Soldiers who
      experienced combat are at increased risk for persistent SSD and comorbidities
      associated with SSD. Efforts to reestablish good sleep habits and aggressive
      evaluation of soldiers with persistent SSD following deployment may aid in the
      prevention and management of associated medical conditions.

PMID- 21886357
TI  - Longitudinal association between short sleep, body weight, and emotional and
      learning problems in Hispanic and Caucasian children.
AB  - STUDY OBJECTIVE: To determine the impact of lower amounts of childhood sleep
      assessed by polysomnogram on development of obesity, being anxious or depressed,
      or having learning problems 5 years later. DESIGN: Prospective cohort.
      PARTICIPANTS: Subjects were 304 community participants from the Tucson Children's
      Assessment of Sleep Apnea study, aged 6-12 years old at baseline. MEASUREMENTS
      AND RESULTS: Children were classified according to baseline sleep as those who
      slept >= 9 h/night, those who slept > 7.5 to < 9 h/night, and those who slept <=
      7.5 h/night. Odds of overweight/obese (>= 85(th) BMI percentile), obese (>=
      95(th) BMI percentile), anxious or depressed, and learning problems at follow-up
      were assessed according to baseline sleep categories. Children who slept <= 7.5
      h/night had higher odds of being obese (OR = 3.3, P < 0.05) at follow-up than
      children who slept >= 9 h/night. Borderline significance for overweight/obese (OR
      = 2.2, P < 0.1), anxious or depressed (OR = 3.3, P < 0.1), and having learning
      problems (OR = 11.1, P < 0.1) were seen for children who slept <= 7.5 h/night as
      compared to those who slept >= 9 h/night. A mean increase in BMI of 1.7 kg/m(2)
      (P = 0.01) over the 5 years of follow-up was seen for children who slept <= 7.5
      h/night compared to those who slept >= 9 h/night. These relationships did not
      differ between Hispanic and Caucasian children. CONCLUSIONS: Children with
      reduced amounts of sleep (<= 7.5 h/night) had an increased risk for higher body
      weight in early adolescence. Similarly, children who slept <= 7.5 h/night had
      higher risk of being anxious or depressed or having learning problems in early
      adolescence.

PMID- 21886358
TI  - Effects of sleep apnea on nocturnal free fatty acids in subjects with heart
      failure.
AB  - STUDY OBJECTIVES: Sleep apnea is common in patients with congestive heart
      failure, and may contribute to the progression of underlying heart disease.
      Cardiovascular and metabolic complications of sleep apnea have been attributed to
      intermittent hypoxia. Elevated free fatty acids (FFA) are also associated with
      the progression of metabolic, vascular, and cardiac dysfunction. The objective of
      this study was to determine the effect of intermittent hypoxia on FFA levels
      during sleep in patients with heart failure. DESIGN AND INTERVENTIONS: During
      sleep, frequent blood samples were examined for FFA in patients with stable heart
      failure (ejection fraction < 40%). In patients with severe sleep apnea (apnea
      hypopnea index = 65.5 +/- 9.1 events/h; average low SpO2 = 88.9%), FFA levels
      were compared to controls with milder sleep apnea (apnea-hypopnea index = 15.4 +/
      3.7 events/h; average low SpO2 = 93.6%). In patients with severe sleep apnea,
      supplemental oxygen at 2-4 liters/min was administered on a subsequent night to
      eliminate hypoxemia. MEASUREMENTS AND RESULTS: Prior to sleep onset, controls and
      patients with severe apnea exhibited a similar FFA level. After sleep onset,
      patients with severe sleep apnea exhibited a marked and rapid increase in FFA
      relative to control subjects. This increase persisted throughout NREM and REM
      sleep exceeding serum FFA levels in control subjects by 0.134 mmol/L (P =
      0.0038). Supplemental oxygen normalized the FFA profile without affecting sleep
      architecture or respiratory arousal frequency. CONCLUSION: In patients with heart
      failure, severe sleep apnea causes surges in nocturnal FFA that may contribute to
      the accelerated progression of underlying heart disease. Supplemental oxygen
      prevents the FFA elevation.

PMID- 21886359
TI  - Sleep disturbances are related to decreased transmission of blue light to the
      retina caused by lens yellowing.
AB  - STUDY OBJECTIVES: Sleep pattern and circadian rhythms are regulated via the
      retinohypothalamic tract in response to stimulation of a subset of retinal
      ganglion cells, predominantly by blue light (450-490 nm). With age, the
      transmission of blue light to the retina is reduced because of the aging process
      of the human lens, and this may impair the photoentrainment of circadian rhythm
      leading to sleep disorders. The aim of the study was to examine the association
      between lens aging and sleep disorders. DESIGN: Cross-sectional population based
      study. SETTING: The study was performed at the Research Center for Prevention and
      Health, Glostrup Hospital, Denmark and at the Department of Ophthalmology, Herlev
      Hospital, Denmark. PARTICIPANTS: An age- and sex-stratified sample of 970 persons
      aged 30 to 60 years of age drawn from a sample randomly selected from the
      background population. INTERVENTIONS: Not applicable. MEASUREMENTS AND RESULTS:
      Sleep disturbances were evaluated by a combination of questionnaire and the use
      of prescription sleeping medication. Lens aging (transmission and yellowing) was
      measured objectively by lens autofluorometry. The risk of sleep disturbances was
      significantly increased when the transmission of blue light to the retina was
      low, even after correction for the effect of age and other confounding factors
      such as smoking habits, diabetes mellitus, gender, and the risk of ischemic heart
      disease (P < 0.0001). CONCLUSIONS: Filtration of blue light by the aging lens was
      significantly associated with an increased risk of sleep disturbances. We propose
      that this is a result of disturbance of photoentrainment of circadian rhythms.

PMID- 21886361
TI  - The effect of sleep deprivation on vocal expression of emotion in adolescents and
      adults.
AB  - STUDY OBJECTIVE: Investigate the impact of sleep deprivation on vocal expression
      of emotion. DESIGN: Within-group repeated measures analysis involving sleep
      deprivation and rested conditions. SETTING: Experimental laboratory setting.
      PATIENTS OR PARTICIPANTS: Fifty-five healthy participants (24 females), including
      38 adolescents aged 11-15 y and 17 adults aged 30-60 y. INTERVENTIONS: A
      multimethod approach was used to examine vocal expression of emotion in
      interviews conducted at 22:30 and 06:30. On that night, participants slept a
      maximum of 2 h. MEASUREMENTS AND RESULTS: Interviews were analyzed for vocal
      expression of emotion via computerized text analysis, human rater judgments, and
      computerized acoustic properties. Computerized text analysis and human rater
      judgments indicated decreases in positive emotion in all participants at 06:30
      relative to 22:30, and adolescents displayed a significantly greater decrease in
      positive emotion via computerized text analysis relative to adults. Increases in
      negative emotion were observed among all participants using human rater
      judgments. Results for the computerized acoustic properties indicated decreases
      in pitch, bark energy (intensity) in certain high frequency bands, and vocal
      sharpness (reduction in high frequency bands > 1000 Hz). CONCLUSIONS: These
      findings support the importance of sleep for healthy emotional functioning in
      adults, and further suggest that adolescents are differentially vulnerable to the
      emotional consequences of sleep deprivation.

PMID- 21886360
TI  - Relationships between menopausal and mood symptoms and EEG sleep measures in a
      multi-ethnic sample of middle-aged women: the SWAN sleep study.
AB  - STUDY OBJECTIVES: Examine associations of vasomotor and mood symptoms with
      visually scored and computer-generated measures of EEG sleep. DESIGN: Cross
      sectional analysis. SETTING: Community-based in-home polysomnography (PSG).
      PARTICIPANTS: 343 African American, Caucasian, and Chinese women; ages 48-58
      years; pre-, peri- or post-menopausal; participating in the Study of Women's
      Health Across the Nation Sleep Study (SWAN Sleep Study). INTERVENTIONS: None.
      MEASUREMENTS AND RESULTS: Measures included PSG-assessed sleep duration,
      continuity, and architecture, delta sleep ratio (DSR) computed from automated
      counts of delta wave activity, daily diary-assessed vasomotor symptoms (VMS),
      questionnaires to collect mood (depression, anxiety) symptoms, medication, and
      lifestyle information, and menopausal status using bleeding criteria. Sleep
      outcomes were modeled using linear regression. Nocturnal VMS were associated with
      longer sleep time. Higher anxiety symptom scores were associated with longer
      sleep latency and lower sleep efficiency, but only in women reporting nocturnal
      VMS. Contrary to expectations, VMS and mood symptoms were unrelated to either DSR
      or REM latency. CONCLUSIONS: Vasomotor symptoms moderated associations of anxiety
      with EEG sleep measures of sleep latency and sleep efficiency and was associated
      with longer sleep duration in this multi-ethnic sample of midlife women.

PMID- 21886362
TI  - The extent of processing of near-hearing threshold stimuli during natural sleep.
AB  - OBJECTIVES: Event-related potential (ERPs) provide an exquisite means to monitor
      the extent of processing of external stimulus input during sleep. The processing
      of relatively high intensity stimuli has been well documented. Sleep normally
      occurs in much less noisy environments. The present study therefore employed ERPs
      to examine the extent of processing of very low intensity (near-hearing
      threshold) stimuli. DESIGN: Brief duration 1000 Hz auditory tone bursts varying
      in intensity at random from -5 to +45 dB from normative hearing level (nHL) in 10
      dB steps were presented every 1.5 to 2.5 s when the subject was awake and reading
      a book and again during all-night sleep. SUBJECTS: n = 10 healthy young adults.
      MEASUREMENTS AND RESULTS: In the waking state, the auditory stimuli elicited a
      negative-going deflection, N1, peaking at about 100 ms, followed by a smaller
      positivity, P2, peaking at about 180 ms. N1-P2 gradually decreased in amplitude
      with decreases in stimulus intensity and remained visible at near-hearing
      threshold levels. During NREM sleep, the amplitude of N1 was at baseline level
      and was reduced to only 15% to 20% of its waking amplitude during REM sleep. P2
      was much larger in sleep than in wakefulness. Importantly, during sleep, P2 could
      be reliably elicited by the auditory stimuli to within 15 dB of threshold. During
      NREM, a large amplitude negativity peaking at about 350 ms was elicited by the
      higher intensity stimuli. This N350 was much reduced in amplitude during REM
      sleep. A significant N350 was not, however, elicited when stimuli intensity
      levels were below 25 dB nHL. CONCLUSIONS: Auditory stimuli that are only slightly
      above hearing threshold appear to be processed extensively during a 200 to 400 ms
      interval in both NREM and REM sleep. The nature of this processing is, however,
      very different compared to the waking state.

PMID- 21886363
TI  - The role of the spontaneous and evoked k-complex in good-sleeper controls and in
      individuals with insomnia.
AB  - STUDY OBJECTIVES: Spontaneous and evoked K-complexes are believed to reflect a
      mechanism of sleep protection, yet their functional role remains a subject of
      debate. Studying the K-complex in primary insomnia, for which sleep protection
      appears to be of central importance, may provide further insight on its role. The
      purpose of the present study was to determine the role of spontaneous and evoked
      K-complexes in good sleepers and to investigate its role in primary insomnia.
      PARTICIPANTS: Twelve individuals with primary insomnia (mean age = 45.4 years)
      and 12 good-sleeper controls (mean age = 44.3 years). METHODS AND PROCEDURE:
      Participants underwent 4 consecutive nights of polysomnographic recordings.
      Spontaneous K-complexes (SKC) were analyzed during continuous stage 2 sleep on
      the third night, whereas evoked K-complexes (EKC) were elicited by auditory
      stimuli on the fourth night. Relative spectral power was measured on 1-second
      electroencephalographic segments prior to and following SKC, EKC, and trials in
      which auditory stimuli did not elicit a K-complex (EKC-). K-complex amplitudes
      were also measured. RESULTS: Measures of relative spectral power showed
      significant changes following EKC (increase in activity in the delta frequency
      band and decrease in activity in the theta, sigma, beta, and gamma frequency
      bands) and SKC (increase in activity in delta frequency band and decrease in
      activity in theta, alpha, sigma, and beta frequency bands) for good sleepers,
      whereas there was no such marked change in electroencephalographic activity
      surrounding EKC-. A similar pattern of electroencephalographic activity was also
      observed for the insomnia group on trials of each different K-complex. Auditory
      stimuli elicited the same proportion of EKC for both groups, whereas SKC density
      was higher for the insomnia group (1.52 SKC/min) than for good sleepers (1.06
      SKC/minute) CONCLUSION: These results suggest that the SKC and the EKC both
      promote deeper sleep, further supporting a sleep-protection role.

PMID- 21886364
TI  - Sleep disturbance impairs stroke recovery in the rat.
AB  - STUDY OBJECTIVES: There is a lack of experimental evidence to support the
      hypothesis that sleep may modulate stroke outcome as suggested by clinical
      observations. We have previously shown that sleep disturbance (SDis) over 3 days
      aggravates brain damage in a rat model of focal cerebral ischemia. The aim of
      this study is to further investigate effects of SDis on long-term stroke recovery
      and neuroplasticity as assessed by axonal sprouting, neurogenesis, and
      angiogenesis. DESIGN: Focal cerebral ischemia was induced by permanent occlusion
      of the distal branches of middle cerebral artery. Twelve hours after initiation
      of ischemia, SDis was performed over 3 consecutive days (deprivation of 80% sleep
      during the 12-h light phase). Weekly assessments on sensorimotor function by the
      single pellet reaching test (SPR) were performed for 5 weeks after surgery.
      Axonal sprouting was evaluated by anterograde tracing with biotinylated dextran
      amine (BDA) and neurogenesis/angiogenesis by bromodeoxyuridine (BrdU) labelling
      along with cell-type markers. Control groups included ischemia without SDis, sham
      with SDis, and sham without SDis. SETTING: Basic sleep research laboratory.
      MEASUREMENTS AND RESULTS: Rats subjected to SDis after ischemia showed
      significantly less recovery of forearm motor skills during the post-stroke period
      of 5 weeks. This effect was accompanied by a substantial reduction in axonal
      sprouting, expression of synaptophysin, and the ischemia-stimulated neural and
      vascular cell proliferation. CONCLUSION: SDis has detrimental effects on
      functional and morphological/structural outcomes after stroke, suggesting a role
      of sleep in the modulation of recovery processes and neuroplasticity.

PMID- 21886366
TI  - Migration and Environmental Hazards.
AB  - Losses due to natural hazards (e.g., earthquakes, hurricanes) and technological
      hazards (e.g., nuclear waste facilities, chemical spills) are both on the rise.
      One response to hazard-related losses is migration, with this paper offering a
      review of research examining the association between migration and environmental
      hazards. Using examples from both developed and developing regional contexts, the
      overview demonstrates that the association between migration and environmental
      hazards varies by setting, hazard types, and household characteristics. In many
      cases, however, results demonstrate that environmental factors play a role in
      shaping migration decisions, particularly among those most vulnerable. Research
      also suggests that risk perception acts as a mediating factor. Classic migration
      theory is reviewed to offer a foundation for examination of these associations.

PMID- 21886367
TI  - Knowledge translation, evidence-based practice, and you.

PMID- 21886365
TI  - Continuous positive airway pressure: evaluation of a novel therapy for patients
      with acute ischemic stroke.
AB  - BACKGROUND: New approaches are needed to treat patients with stroke. Among acute
      ischemic stroke patients, our primary objectives were to describe the prevalence
      of sleep apnea and demonstrate the feasibility of providing auto-titrating
      continuous positive airway pressure (auto-CPAP). A secondary objective was to
      examine the effect of auto-CPAP on stroke severity. METHODS: Stroke patients
      randomized to the intervention group received 2 nights of auto-CPAP, but only
      those with evidence of sleep apnea received auto-CPAP for the remainder of the 30
      day period. Intervention patients received polysomnography 30 days post-stroke.
      Control patients received polysomnography at baseline and after 30 days.
      Acceptable auto-CPAP adherence was defined as >= 4 h/night for >= 75% nights.
      Change in stroke severity was assessed comparing the NIH Stroke Scale (NIHSS) at
      baseline versus at 30 days. RESULTS: The 2 groups (intervention N = 31, control N
      = 24) had similar baseline stroke severity (both median NIHSS, 3.0). Among
      patients with complete polysomnography data, the majority had sleep apnea:
      baseline, 13/15 (86.7%) control patients; 30 days, 24/35 (68.6%) control and
      intervention patients. Intervention patients had greater improvements in NIHSS (
      3.0) than control patients (-1.0); P = 0.03. Among patients with sleep apnea,
      greater improvement was observed with increasing auto-CPAP use: -1.0 for control
      patients not using auto-CPAP; -2.5 for intervention patients with some auto-CPAP
      use; and -3.0 for intervention patients with acceptable auto-CPAP adherence.
      CONCLUSIONS: The majority of acute stroke patients had sleep apnea. Auto-CPAP was
      well tolerated, appears to improve neurological recovery from stroke, and may
      represent a new therapeutic approach for selected patients with acute cerebral
      infarction.

PMID- 21886368
TI  - Patients are satisfied with advanced practice physiotherapists in a role
      traditionally performed by orthopaedic surgeons.
AB  - PURPOSE: To measure and compare patient satisfaction with follow-up care in
      advanced practice physiotherapist (APP) and orthopaedic surgeon clinics for
      patients following total hip or knee replacement. METHOD: Consecutive patients
      attending either an APP-led or a surgeon-led review clinic were surveyed using a
      modified nine-item satisfaction questionnaire based on the Visit-Specific
      Satisfaction Instrument (VSQ-9). Chi-square analyses were used to examine
      differences in patient characteristics and type of visit. Independent t-tests
      were used to examine potential differences in patient satisfaction. RESULTS: Of
      the 123 participants, more than half were aged 65 years or older. Chi-squared
      analyses revealed no significant difference in participant characteristics
      (gender, age, and overall health status) between the two different types of
      clinics. There was a significant difference (chi(2) (4)=12.49, p=0.014) in the
      distribution of the timing of follow-up appointments. There was no significant
      difference between the groups in mean overall patient satisfaction scores on the
      modified VSQ-9 (p=0.34) nor in the mean of the sum of the seven items related to
      the service provider (p=0.85). Satisfaction scores for most of the service
      provider items were above 90/100. CONCLUSION: Patients are highly satisfied with
      the care provided by APPs in follow-up clinics after joint replacement.
      Evaluation of the patient perspective is essential to any new role involving a
      shift in traditional practice boundaries.

PMID- 21886369
TI  - Clinician's Commentary.

PMID- 21886370
TI  - Case Report: Schizophrenia Discovered during the Patient Interview in a Man with
      Shoulder Pain Referred for Physical Therapy.
AB  - PURPOSE: The purpose of this case report is to demonstrate the importance of a
      thorough patient interview. The case involves a man referred for physical therapy
      for a musculoskeletal dysfunction; during the patient interview, a psychiatric
      disorder was recognized that was later identified as schizophrenia. A secondary
      purpose is to educate physical therapists on the recognizable signs and symptoms
      of schizophrenia.Client description: A 19-year-old male patient with chronic
      shoulder, elbow, and wrist pain was referred for physical therapy. During the
      interview, the patient reported that he was receiving signals from an electronic
      device implanted in his body.Measures and outcome: The physical therapist's
      initial assessment identified a disorder requiring medical referral. Further
      management of the patient's musculoskeletal dysfunction was not appropriate at
      this time. INTERVENTION: The patient was referred for further medical
      investigation, as he was demonstrating signs suggestive of a psychiatric
      disorder. The patient was diagnosed with schizophrenia by a psychiatrist and was
      prescribed Risperdal. IMPLICATIONS: This case study reinforces the importance of
      a thorough patient interview by physical therapists to rule out non
      musculoskeletal disorders. Patients seeking neuromusculoskeletal assessment and
      treatment may have undiagnosed primary or secondary psychiatric disorders that
      require recognition by physical therapists and possible medical referral.

PMID- 21886371
TI  - An interdisciplinary pain rehabilitation programme: description and evaluation of
      outcomes.
AB  - PURPOSE: The purpose of this archival report is to describe the essential
      elements of an intensive 8-week interdisciplinary pain rehabilitation programme
      (IPRP) with a cognitive-behavioural emphasis and the results that can be expected
      in treating patients with chronic pain conditions. METHOD: This report describes
      a private outpatient program providing treatment services to patients with long
      term disabling pain arising from work- or accident-related musculoskeletal
      injuries. The cohort consists of 338 consecutive patients who completed the
      program over a 3-year period (patients discharged between January 1, 2005, and
      December 31, 2007). RESULTS: Improvements in vocational status were noted in 75%
      of patients with chronic pain. Patients were also able to reduce their pain
      levels by approximately 16% and to reduce their levels of anxiety and depression
      by 13% and 17% respectively. At the same time, 61% of patients were able to
      reduce or eliminate their pain medications. CONCLUSIONS: Outcomes are consistent
      with evidence-based clinical practice guidelines for the management of chronic
      pain conditions. The published literature supports the efficacy of this
      interdisciplinary approach in highly disabled patients for whom effective
      treatment has been delayed. Early intervention in the subacute phase is
      recommended for prevention of long-term disability in patients with chronic pain.

PMID- 21886373
TI  - Ethics of involving children in health-related research: applying a decision
      making framework to a clinical trial.
AB  - PURPOSE: This paper explores ethical issues related to the involvement of
      children in health-related research through the application of a conceptual model
      (the Miller and Kenny framework) to a current clinical trial on casting protocols
      for equinus gait of children with cerebral palsy (CP). SUMMARY OF KEY POINTS: The
      direct involvement of children in health-related research is important for
      maintaining and improving standards of paediatric clinical care. Ethical
      considerations around investigations involving this highly vulnerable population
      are complex, however, requiring the involvement of many levels of decision makers
      government, research ethics boards (REBs), health care providers, parents, and
      children. The Miller and Kenny framework is useful in distinguishing these levels
      and heightening awareness of the complexities of the issues around engaging
      children in research. Considerations include the role of parents/caregivers in
      decision making, individual assessment of the child's decisional capacities,
      close attention to the child's context and life experience, provision of
      developmentally appropriate information about the research study, and careful
      assessment of dissent prior to withdrawing the child from the study.
      RECOMMENDATIONS: Physical therapists involved in paediatric clinical practice
      and/or research must be knowledgeable about ethical principles, policies, and REB
      requirements. The Miller and Kenny framework is a helpful guide to clarify
      decision-making roles around children's participation in research.

PMID- 21886372
TI  - Procedural pain management for children receiving physiotherapy.
AB  - PURPOSE: This article provides an overview of literature relevant to the
      prevention and relief of pain and distress during physiotherapy procedures, with
      guidance for physiotherapists treating children. SUMMARY OF KEY POINTS:
      Physiotherapists are generally well trained in assessing and managing pain as a
      symptom of injury or disease, but there is a need to improve the identification
      and management of pain produced by physiotherapy procedures such as stretching
      and splinting. In contrast to physiotherapy, other health care disciplines, such
      as dentistry, nursing, paediatrics, emergency medicine, and paediatric
      psychology, produce extensive literature on painful procedures. Procedural pain
      in children is particularly important because it can lead to later fear and
      avoidance of necessary medical care. RECOMMENDATIONS: We emphasize the need for
      physiotherapists to recognize procedural pain and fear in the course of treatment
      using verbal, nonverbal, and contextual cues. We present many methods that
      physiotherapists can use to prevent or relieve procedural pain and fear in
      paediatric patients and provide an example of a simple, integrated plan for
      prevention and relief of distress induced by painful procedures.

PMID- 21886374
TI  - The provision of weekend physiotherapy services in tertiary-care hospitals in
      Canada.
AB  - PURPOSE: To describe the provision of weekend physiotherapy (PT) services in
      tertiary-care hospitals in Canada. METHODS: A prospective cross-sectional survey
      was conducted across tertiary-care hospitals, defined as those with university
      affiliation and at least one intensive care unit (ICU). Data were collected via
      telephone-administered questionnaires addressing hospital demographics, weekend
      staffing, workload, and weekend referral criteria. RESULTS: A response rate of
      84% (n=36) was obtained. Of facilities providing weekend PT services (97%), 35
      (100%) provided care on Saturdays, 32 (91%) on Sundays, and 33 (94%) on statutory
      holidays. Weekend services were staffed using permanent full-time (n=35; 100%) or
      part-time (n=28; 80%) in-patient staff or outsourced staff (n=1; 3%). The number
      of physiotherapists available on the weekend was smaller than the number
      available during the week (p<0.001). Common weekend referral criteria included
      cardiorespiratory problems (n=35; 100%), postoperative assessment of patients at
      risk for deterioration (n=32; 91%), and patients scheduled for discharge pending
      PT assessment (n=30; 86%). CONCLUSION: Both the scope and the number of staff
      available to provide PT services were less on the weekend than during the week.
      Despite the use of common criteria for weekend referral, variability in this
      service exists. Knowledge pertaining to current weekend PT services provides
      opportunities for harmonization of service delivery.

PMID- 21886375
TI  - Clinicians' commentary.

PMID- 21886376
TI  - Modifiable Risk Factors Identify People Who Transition from Non-fallers to
      Fallers in Community-Dwelling Older Adults: A Prospective Study.
AB  - PURPOSE: To identify modifiable risk factors associated with the transition from
      non-faller to faller in community-dwelling older adults. METHOD: A prospective
      study design was used. Adults aged 60 to 90 years (n=90, mean age=79.7 years, 63%
      male) who did not report falling in the past year were included. A comprehensive
      geriatric assessment was performed at study baseline, and daily falls data were
      collected monthly for 1 year. Multivariable regression using a modified Poisson
      model on fall status (yes/no) and a Cox proportional hazards model for time to
      first fall were used to identify risk factors. RESULTS: Twenty-four people (27%)
      fell. Modifiable risk factors were present in 67% of study participants, and fall
      risk increased as the number of risk factors increased. The most common
      activities performed prior to falling were walking and using stairs. Fall risk
      doubled ([relative risk=2.00; 95%CI: 1.13-3.56) per unit increase in the number
      of risk factors (lower-extremity weakness, balance impairment, and >=4
      prescription medications). CONCLUSIONS: Among older adults who were self-reported
      non-fallers, falls were a common outcome, and modifiable risk factors were
      present in the majority of the sample. The absence of a fall history does not
      rule out the need to screen for other risk factors for falls. Functional lower
      extremity weakness, balance impairment as measured by the Berg Balance Scale
      (score <50), and number of risk factors were independent predictors for the
      transition in status from non-faller to faller. Further research is required to
      define effective interventions to prevent first falls.

PMID- 21886377
TI  - Pulmonary rehabilitation: overwhelming evidence but lost in translation?
AB  - PURPOSE: This report highlights the current international gap between the
      availability of high-quality evidence for pulmonary rehabilitation (PR) and its
      low level of implementation. Key barriers are outlined, and potentially effective
      strategies to improve implementation are presented. SUMMARY OF KEY POINTS:
      Although pulmonary rehabilitation (PR) is recommended by international guidelines
      as part of the management of patients with chronic obstructive pulmonary disease
      (COPD), participation in PR remains low. Physician referral to PR ranges from 3%
      to 16% of suitable patients. Barriers to participation include limited
      availability of suitable programmes and interrelated issues of referral and
      access. Individual patient barriers, including factors relating to comorbidities
      and exacerbations, perceptions of benefit, and ease of access, contribute less
      overall to low participation rates. Chronic care programmes that incorporate self
      management support have some benefit in patients with COPD. However, the
      demonstrated cost-effectiveness of PR is substantial, and efforts to improve its
      implementation are urgently indicated. CONCLUSION: To improve implementation, a
      holistic examination of the key issues influencing a patient's participation in
      PR is needed. Such an examination should consider the relative influences of
      environmental (e.g., health-service-related) factors, organizational factors
      (e.g., referral and intake procedures), and individual factors (e.g., patient
      barriers) for all participants. On the basis of these findings, policy, funding,
      service delivery, and other interventions to improve participation in PR can be
      developed and evaluated.

PMID- 21886378
TI  - Clinician's Commentary.

PMID- 21886379
TI  - Modelling knee range of motion post arthroplasty: clinical applications.
AB  - PURPOSE: To model change in knee range of motion (ROM) post total knee
      arthroplasty (TKA) and to show how this information can be incorporated into
      clinical decision making. METHOD: We applied a variable-occasion repeated
      measures study design. Patients' knee flexion and extension ROM were assessed pre
      and post arthroplasty over the ensuing 60 weeks. We examined change in ROM post
      TKA using linear and nonlinear mixed-effects modelling, and examined whether age,
      body mass index, prearthroplasty ROM, and gender were determinants of recovery in
      post-arthroplasty ROM. RESULTS: Of 93 eligible patients, 74 provided pre- and
      post-arthroplasty data. A random intercept nonlinear model fit the flexion data
      best, and a random intercept linear model fit the extension data best. Pre
      arthroplasty ROM was found to be a determinant of recovery in ROM post
      arthroplasty. This finding was common to both flexion and extension models.
      CONCLUSIONS: Our study showed that the greatest improvement for knee ROM took
      place during the first 12 weeks post arthroplasty. Of the variables examined,
      only pre-arthroplasty ROM was a determinant of outcome (p<0.05). The study
      results provide clinicians with data to determine expected rates of improvement
      for patients as well as the projected maximum ROM, facilitating improved clinical
      decision making.

PMID- 21886380
TI  - The effect of modified constraint-induced movement therapy on spasticity and
      motor function of the affected arm in patients with chronic stroke.
AB  - PURPOSE: The purpose of this study was to explore the effect of modified
      constraint-induced movement therapy (CIMT) in a real-world clinical setting on
      spasticity and functional use of the affected arm and hand in patients with
      spastic chronic hemiplegia. METHOD: A prospective consecutive quasi-experimental
      study design was used. Twenty patients with spastic hemiplegia (aged 22-67 years)
      were tested before and after 2-week modified CIMT in an outpatient rehabilitation
      clinic and at 6 months. The Modified Ashworth Scale (MAS), active range of motion
      (AROM), grip strength, Motor Activity Log (MAL), Sollerman hand function test,
      and Box and Block Test (BBT) were used as outcome measures. RESULTS: Reductions
      (p<0.05-0.001) in spasticity (MAS) were seen both after the 2-week training
      period and at 6-month follow-up. Improvements were also seen in AROM (median
      change of elbow extension 5 degrees , dorsiflexion of hand 10 degrees ), grip
      strength (20 Newton), and functional use after the 2-week training period (MAL: 1
      point; Sollerman test: 8 points; BBT: 4 blocks). The improvements persisted at 6
      month follow-up, except for scores on the Sollerman hand function test, which
      improved further. CONCLUSION: Our study suggests that modified CIMT in an
      outpatient clinic may reduce spasticity and increase functional use of the
      affected arm in spastic chronic hemiplegia, with improvements persisting at 6
      months.

PMID- 21886381
TI  - Reliability of the assessment of mother-infant sensitivity-chinese version for
      preterm and term taiwanese mother-infant dyads.
AB  - PURPOSE: The objectives of this study were to translate and modify the Assessment
      of Mother-Infant Sensitivity scale into a Chinese version (modified AMIS-C) and
      to examine its reliability with preterm and term Taiwanese mother-infant dyads.
      METHOD: A total of 241 mother-infant pairs (179 preterm dyads and 62 term dyads)
      were prospectively recorded and their behaviour in feeding assessed using the
      modified AMIS-C when infants were at 4 and 6 months corrected age. A subset of
      the sample was used for interrater reliability testing, and the whole sample was
      used for assessment of internal consistency. RESULTS: Interrater reliability was
      high for the modified AMIS-C section and total scores (intra-class correlation
      coefficients=0.91-0.99). Internal consistency was good to excellent for the
      maternal section and total score (alpha=0.71-0.86) and was fair to good for the
      infant and dyadic section score (alpha=0.44-0.75). CONCLUSIONS: The modified AMIS
      C scale is a clinically feasible and reliable instrument for assessing mother
      infant interaction of preterm and term dyads during early infancy.

PMID- 21886382
TI  - What Does the Cochrane Collaboration Say about Rehabilitation of Walking?

PMID- 21886383
TI  - Physiotherapy Canada volume 62, annual index - 2010.

PMID- 21886385
TI  - Beaches and HABs: Successful Expansion of the Florida Red Tide Reporting System
      for Protection of Public Health through Community Education and Outreach.

PMID- 21886386
TI  - Editorial.

PMID- 21886387
TI  - Hematologic changes in visceral leishmaniasis/kala azar.
AB  - Visceral Leishmaniasis (VL) or Kala Azar is a chronic infectious disease caused
      by parasites of the Leishmania donovani complex that can cause various
      hematologic manifestations. It is characterized by fever, enlargement of liver
      and spleen, weight loss, pancytopenia and hypergammaglobinemia. It is endemic in
      the Indian subcontinent, mainly seen in the states of Bihar and West Bengal.
      Patients with VL can present to the haematologist for various haematological
      problems prior to receiving the diagnosis of VL. Anaemia is the most common
      haematological manifestation of VL. VL may also be associated with leucopenia,
      thrombocytopenia, pancytopenia, hemophagocytosis and disseminated intravascular
      coagulation. Hematological improvement is noted within a week and complete
      hematological response occurs in 4-6 weeks of treatment. Relapses are rare and
      increased risk of being diagnosed with hematolymphoid malignancies on long term
      follow up is not noted.

PMID- 21886384
TI  - ELECTROPHYSICAL AGENTS - Contraindications And Precautions: An Evidence-Based
      Approach To Clinical Decision Making In Physical Therapy.

PMID- 21886388
TI  - Clinical Features of Bone Complications and Prognostic Value of Bone Lesions
      Detected by X-ray Skeletal Survey in Previously Untreated Patients with Multiple
      Myeloma.
AB  - Multiple myeloma is usually associated with the presence of lytic bone lesions.
      We reviewed the clinical and laboratory features of patients with newly diagnosed
      myeloma bone disease and evaluated the prognostic significance of different X-ray
      image patterns in symptomatic MM patients. We retrospectively reviewed 260
      patients with newly diagnosed MM. X-ray image patterns of patients were
      correlated with hematologic parameters, therapeutic reaction and patient
      survival. Patients with the X-ray imaging pattern of grade 2-4 had significantly
      higher marrow plasma cells levels, marrow CD138(+) D38(+) cell percentage, ECOG
      performance score, and serum IL-6 level than grade 0-1. Univariate analysis
      demonstrated that skeletal lytic changes associated with rapid progression. There
      is a high incidence of myeloma bone disease (MBD) in patients of MM in China.
      Patients of extensive bone lesions have more severe alterations in hematologic
      parameters than do those without bone lesions and severe bone lesions is an
      important adverse prognostic factor associated with a short TTP.

PMID- 21886389
TI  - Prevalence of transfusion transmitted infections in voluntary and replacement
      donors.
AB  - The aim of the study was to find out the prevalence of transfusion transmitted
      infections (TTI) in voluntary and replacement donors. A total of 9599 donors were
      analysed for the prevalence of TTI over a period of 2 years.Of these 61.2% were
      voluntary donors and 38.8% were replacement donors. Prevalence of TTI in total
      donors was 0.6%. Prevalence of hepatitis B was highest (0.34%) followed by
      syphilis (0.11%), HIV&HCV (0.06%) and malaria (0.01%). Prevalence was more in
      male replacement donors. Extensive donor selection and screening procedures will
      help in improving the blood safety.

PMID- 21886390
TI  - Transfusion associated graft versus host disease following whole blood
      transfusion from an unrelated donor in an immunocompetent patient.
AB  - Graft-versus-host disease (GVHD) is a well-known complication of allogeneic bone
      marrow transplantation. Transfusion associated graft-versus-host disease (TA
      GVHD) is much less common and nearly uniformly fatal complication of blood
      transfusion. The risk factors underlying the development of TA- GVHD are
      incompletely defined, but it is commonly seen in individuals with congenital or
      acquired immunodeficiency, transfusions from blood relatives, intrauterine
      transfusions and HLA-matched platelet transfusions. Diagnosis of TA-GVHD may be
      difficult at a time due to rarity in occurrence and overlapping clinical features
      with various infections and drug reactions. We describe a case of transfusion
      associated GVHD that occurred after transfusion of whole blood from unrelated
      donor in an immunocompetent patient.

PMID- 21886391
TI  - Chronic myeloid leukemia presenting with visual and auditory impairment in an
      adolescent: an insight to management strategies.
AB  - A 15-year-old girl presented with progressive deterioration in vision and hearing
      over 1 week. A huge spleen was palpated below the left costal margin laying down
      to inguinal region. Blood count showed hyperleukocytosis with a white blood cell
      count of 455 * 10(9)/l. Peripheral smear yielded myeloid precursor cells with
      basophilia. Bone marrow aspiration revealed a blast count of 5% morphologically
      and 4% by flow cytometry. Fundoscopic examination revealed bilateral retinal
      exudates, edema and hemorhages. Partial sensorioneural hearing loss was also
      detected on the right ear. The diagnosis of chronic myeloid leukemia was
      confirmed by positive t(9;22) by RT-PCR. After commencing on hydroxyurea and
      intrathecal methotrexate-prednisolone, progressive improvement in hearing and
      vision was obtained. In our brief report, we aimed to emphasize rare presentation
      with visual and hearing impairment of chronic myeloid leukemia during childhood,
      especially in "chronic phase".

PMID- 21886392
TI  - Acute psychosis: a presentation of cyanocobalamin deficiency megaloblastic
      anemia.
AB  - Cyanocobalamin deficiency is not rare in India. Patients present with
      megaloblastic anemia, pancytopenia and sometimes neuropsychiatric manifestations.
      Subacute combined degeneration of the cord, peripheral neuropathy, dementia,
      psychotic depression and paranoid schizophrenia are well reported. We are
      reporting a case of cyanocobalamine deficiency anemia who presented with acute
      psychosis which readily reversed on cyanocobalamin replacement.

PMID- 21886393
TI  - Hemolytic Anemia as a Presenting Feature of Wilson's Disease: A Case Report.
AB  - Wilson's disease is a rare inherited disorder of copper metabolism causing severe
      damage to vital organs. Liver and brain disorders are the main manifestations.
      Severe hemolytic anemia is an unusual complication of Wilson's disease. We
      present a case who developed spherocytic acute hemolytic anemia (Coomb's
      negative) as the initial manifestation of Wilson's disease. On examination Kayser
      Fleischer ring was found. Laboratory data supported a diagnosis of Wilson's
      disease.

PMID- 21886394
TI  - Trisomy 9 in a Patient with Acute Myelogenous Leukaemia FAB Type M2: A Rare
      Occurrence.
AB  - Complete trisomy 9 is a rare cytogenetic abnormality in haematological
      malignancies. Here we present the case history of a patient with clinical
      diagnosis of acute myeloblastic leukaemia (FAB type M2) and having trisomy 9 with
      adverse outcome.

PMID- 21886395
TI  - A Case of Primary Bone Marrow B-Cell Non Hodgkin's Lymphoma with Severe
      Thrombocytopenia: Case Report and A Review of the Literature.
AB  - A 78-year-old man presented with persistent gingival bleeding. He had low
      platelet count of 1.0 * 10(9)/L without any lymphadenopathy. Bone marrow specimen
      showed diffusely distributed small-sized lymphocytes. Combined with
      immunophenotypic analysis, a diagnosis of primary bone marrow B-cell non
      Hodgkin's lymphoma was made. Thrombocytopenia was considered to be caused by
      autoimmune destruction of platelets.

PMID- 21886396
TI  - Philadelphia chromosome positive chronic myelogenous leukemia in a child: a case
      report.
AB  - Philadelphia chromosome (Ph(1))-positive Chronic Myelogenous Leukemia (CML) in a
      child below the age of 3 years is extremely rare. We have reported such a case in
      a 3 year old male child. Peripheral blood smear revealed features of CML and
      karyotypic study showed (Ph(1)) positivity. Biologic behaviour and prognosis are
      similar to that of adult-type of CML.

PMID- 21886397
TI  - Transformation of myelodysplastic syndrome to acute lymphoblastic leukemia in a
      child.
AB  - Childhood myelodysplastic syndrome (MDS) is an uncommon condition. Unlike adult
      MDS, pediatric patients have a more progressive course and rapidly transform to
      acute myeloid leukemia. Evolution to acute lymphoblastic leukemia is extremely
      rare. We report a 5 year old female child who presented with refractory anemia
      with excess blasts and transformed into acute lymphoblastic leukemia 4 months
      after initial diagnosis.

PMID- 21886398
TI  - Treatment of myelodysplastic syndrome transforming into acute myelogenous
      leukemia with azacytidine: a retrospective study from cancer centre in northern
      India.

PMID- 21886399
TI  - Miliary tuberculosis with hemophagocytosis in a two months old infant.
AB  - A two months old male infant, presented with fever, hepatosplenomegaly and
      pancytopenia. On bone marrow aspirate, hemophagocytosis was noted. Trephine
      biopsy showed epithelioid granulomas. ZN stain AFB detected, which confirmed the
      diagnosis of miliary tuberculosis. This case highlights the rare association of
      hemophagocytic syndrome with tuberculosis in infancy.

PMID- 21886400
TI  - Immunophenotypic profile in acute infectious mononucleosis mimicking malignant
      lymphoproliferative disorder: a case report and review of literature.
AB  - Infectious mononucleosis is characterized by an intensive lymphoproliferation
      with atypical forms which sometimes resemble with acute leukemia or malignant
      lymphoproliferative diseases. Flow cytometric analysis of lymphocytes shows a
      typical phenotype but unawareness of it may lead to misdiagnosis of malignant
      lymphoproliferative diseases. Herewith we present an immunophenotypic profile in
      a case of acute infectious mononucleosis and review of literature.

PMID- 21886401
TI  - Screening for G6PD Deficiency in Blood Donor Population.

PMID- 21886402
TI  - "Novel strategies to Improve Recombinant Factor VIII Production and its in vivo
      Recovery".

PMID- 21886403
TI  - Subacute Sensorimotor Polyneuropathy as Sole Manifestation of Occult Non
      Hodgkin's Lymphoma: Infiltrative or Paraneoplastic?

PMID- 21886405
TI  - An in vitro analysis of wear resistance of commercially available acrylic denture
      teeth.
AB  - Posterior denture teeth wear faster than the anterior teeth, causing occlusal
      prematurities and loss of vertical dimension of occlusion. The loss of vertical
      dimension of occlusion lays more stress on the anterior alveolar ridge, which in
      turn increases the rate of residual ridge resorption and causes loss of alveolar
      ridge height in the anterior segment and compromises esthetics. Hence it is
      important for the clinician to choose acrylic resin teeth with high wear
      resistance. The objective of the study is to investigate and compare the wear
      resistance of three different commercially available acrylic resin denture teeth.
      60 specimens were tested for wear resistance in terms of loss of weight and loss
      in volume on a wear and friction monitor for 5,000 cycle wear periods (total of
      10,000 cycles) under a 0.20 kg load. STATISTICAL ANALYSIS USED: The findings were
      analyzed using one way analysis of variance (ANOVA) and Tukey HSD test.
      Comparison of weight loss and volume loss between Surana ultradent, Premadent and
      Dentek showed highly significant difference, Surana ultraddent having better wear
      resistance. Surana ultradent acrylic resin denture had highest wear resistance
      amongst the three groups of tested samples.

PMID- 21886404
TI  - Bruxism: a literature review.
AB  - Bruxism is a movement disorder characterized by grinding and clenching of teeth.
      Awake bruxism is found more in females as compared to males while sleep bruxism
      shows no such gender prevalence. Etiology of bruxism can be divided into three
      groups psychosocial factors, peripheral factors and pathophysiological factors.
      Treatment modalities involve occlusal correction, behavioural changes and
      pharmacological approach. A literature search was performed using National
      Library of Medicine's (NLM) Medical Subject Headings (MeSH) Database, Pubmed and
      Google search engines. The search term 'Bruxism' yielded 2,358 papers out of
      which 230 were review papers. Most of the papers selected were recently published
      during the period of 1996-2010 and very few of them were published before 1996.

PMID- 21886406
TI  - Investigation of marginal fit and surface roughness of crowns, due to different
      bench set and different burnout temperature using base metal alloy.
AB  - The conventional investing technique is used most commonly for casting. Inspite
      of the popularity of this technique, it is very time consuming. To save time of
      the patient, dentist and dental laboratory technician, accelerated casting
      technique can be used. This study uses different bench set and different burnout
      temperatures and has been carried to investigate their effects on marginal fit
      and surface roughness. A total of 40 wax patterns were made simulating the
      artificial crown from the first master die and 20 rectangular wax patterns were
      made from the second master die. Twenty castings simulating the crown and 10
      castings of rectangular plates were obtained by short protocol represented as
      Group A and C, similarly the remaining castings were obtained by standard
      protocol and represented as Group B and D. Marginal discrepancy of both Group A
      and B were determined by using Travelling microscope, whereas Perthometer was
      used for quantitative evaluation of average surface roughness of both Group C and
      D. Scanning electron microscope evaluated the surface roughness qualitatively for
      the specimens of both Groups C and D. The obtained values of Group A and C and
      Group C and D were subjected to statistical analysis. Qualitative analysis of
      Group C and D were done. Accelerated/short protocol gives similar results in
      terms of marginal fit and surface roughness as compared to the
      conventional/standard protocol and is definitely a time saving procedure.

PMID- 21886407
TI  - Effect of recasting of nickel: chromium alloy on its castability.
AB  - Castability plays an important role in selection of an alloy for cast dental
      restorations. This study was conducted to assess the effect of recasting of
      nickel-chromium alloy on its castability. Different percentage combinations of
      new and once casted alloy were used to produce a total of twentyfive cast samples
      using modified Whitlock's method and castings obtained from new alloy were used
      as control group. Castability value was obtained by using Whitlock's formula.
      Results were analyzed using student 't' test. There is no statistical difference
      between the castability value of the new alloy and the recasted alloy (confidence
      level 95%). Within the limitations of the study it is concluded that the
      castability value will not be affected by recasting the nickel-chromium alloy.
      Complete castings of any metal restoration are mandatory and to know the
      completeness of castings of any alloy, castability test is of prime importance.

PMID- 21886408
TI  - A study on self centering of face bows.
AB  - Hanau spring bow has been in use since 1986. Hanau spring bow is claimed to
      maintain self centering property when it is positioned in the patient as well as
      in the articulator. However there is no documented evidence to prove that
      feature. Mainly it was due to the absence of a testing device. Exclusively for
      the present study, the testing device consisting of a platform, stops and
      distance measuring system was designed by the third author. This study proved
      that Hanau has the capability of self centering.

PMID- 21886409
TI  - Study of Biomechanics of Porous Coated Root Form Implant Using Overdenture
      Attachment: A 3D FEA.
AB  - The purpose of this article is to do a three-dimensional finite element stress
      analysis, in relation to root form implant supported by overdenture attachment,
      during axial and non-axial loading. Two porous coated Titanium-aluminum-vanadium
      (Ti-6Al-4V) implants with overdenture abutment were embedded in both simple and
      3D model of interforaminal region of mandible. The material properties of tissue
      ingrowth bonded interface were calculated considering Iso-Strain condition. The
      masticatory forces: axial load of 35 N, a horizontal load of 10 N, and an oblique
      load of 120 N, was applied for the two qualities of cancellous bone. It implied
      that porous topography of the implant led to optimal stress transfer at the
      tissue ingrowth bonded interface and insignificant punching stress at the apex
      than a smooth surface implant. The inferior bone quality was deformed even under
      physiologic loads and showed wider stress pattern. Simulated implant abutment to
      implant bone interface stress may be significantly affected by the quality of the
      bone and the surface topography of the implant. The interface is affected to a
      lesser extent by the prosthetic material properties. Threedimensional anatomical
      model was more close to reality than the geometry of much simpler altered models.

PMID- 21886410
TI  - A study to evaluate the retentive ability of different denture adhesive
      materials: an in vitro study.
AB  - Denture Adhesives are commonly used by denture wearers to enhance the retentive
      ability of their dentures however, little is known about the efficacy of these
      materials. To compare the retentive ability of three different commercially
      available denture adhesives. To find out the best available denture adhesive
      material. An in vitro investigation to evaluate the retentive ability of three
      commercially available denture adhesive powders and two adhesive pastes was
      conducted. The adhesion and cohesion that developed between the glass surface and
      acrylic resin samples when the various materials were interposed between them was
      evaluated by means of a testing apparatus. Denture adhesives increase the
      adhesion of resin samples to the glass surface. Fixon powder showed the highest
      resistance to dislodgement. The paste forms were found to be more retentive.
      Denture adhesives when used in combination with synthetic saliva showed the
      maximum value.

PMID- 21886411
TI  - Efficacy of different disinfectant systems on alginate and addition silicone
      impression materials of Indian and international origin: a comparative
      evaluation.
AB  - Study was planned to evaluate the efficacy of commonly used disinfectants and to
      study qualitatively and quantitatively the persistence of microflora on the
      untreated (control group) and the disinfected impression surface after 24 h.
      Disinfectant systems used were immersion systems like glutaraldehyde, sodium
      hypochlorite and the ultraviolet chamber. The effect of disinfectant on most
      commonly used Indian impression materials was carried out in this study and
      results compared with the most commonly used foreign brands for irreversible
      hydrocolloid and addition silicone. Impressions were made of 25 healthy
      volunteers. These were disinfected and incubated in an incubator for 24 h at 37
      degrees C for aerobic organisms. The inoculation in nutrient media was done to
      test the viability of microorganisms that can persist after rinsing and
      disinfection of the impression surface. The colony forming units were counted and
      compared with that of control group. Control group of all the impression material
      samples showed growth of Streptococcus viridans, Diphtheroids, Streptococcus
      pneumoniae to a greater extent. The growth of Candida albicans, Pseudomonas
      aerugenosa and Staphyloccus albus was present in all the groups but to a lesser
      extent. The persistence of the microflora on the impression surface of both the
      studied brands was similar but the concentration of organisms in the alginate
      control group was two folds as compared to addition silicone group. Use of
      ultraviolet chamber gave better results compared to the studied immersion
      systems. All the disinfection systems were effective in reducing the microbial
      load with ultraviolet chamber as the most effective.

PMID- 21886412
TI  - Prosthetic rehabilitation of ocular defect using digital photography: a case
      report.
AB  - The fundamental objective in restoring a congenital as well as acquired defect of
      eye with an ocular prosthesis is to enable the patient to cope better with the
      difficult process of rehabilitation after an enucleation or evisceration. A
      cosmetically acceptable prosthesis is that reproduces the color, form and
      orientation of iris and allows the patient to return to accustomed lifestyle. A
      sequence of steps for construction of custom-made ocular prostheses is outlined
      in this case report using the advantages of digital imaging technique.

PMID- 21886413
TI  - Long term rehabilitation of a total glossectomy patient.
AB  - Malignant tumours of the oral cavity that require resection of the tongue result
      in severe deficiencies in speech and deglutition. Speech misarticulation leads to
      loss of speech intelligibility, which can prevent or limit communication.
      Prosthodontic rehabilitation involves fabrication of a Palatal Augmentation
      Prosthesis (PAP) following partial glossectomy and a mandibular tongue prosthesis
      after total glossectomy [1]. Speech analysis of a total glossectmy patient
      rehabilitated with a tongue prosthesis was done with the help of Dr. Speech
      Software Version 4 (Tiger DRS, Inc., Seattle) twelve years after treatment.
      Speech therapy sessions along with a prosthesis helped him to correct the dental
      sounds by using the lower lip and upper dentures (labio-dentals). It was noticed
      that speech intelligibility, intonation pattern, speech articulation and overall
      loudness was noticeably improved.

PMID- 21886414
TI  - Angiographic analysis of blood flow modification in cerebral aneurysm models with
      a new asymmetric stent.
AB  - We have built new asymmetric stents for minimally invasive endovascular treatment
      of cerebral aneurysms. Each asymmetric stent consists of a commercial stent with
      a micro-welded circular mesh patch. The blood flow modification in aneurysm
      vessel phantoms due to these stents was evaluated using x-ray angiographic
      analysis. However, the density difference between the radiographic contrast and
      the blood gives rise to a gravity effect, which was evaluated using an initial
      optical dye-dilution experiment. For the radiographic evaluations, curved-vessel
      phantoms instead of simple straight side-wall aneurysm phantoms were used in the
      characterization of meshes/stents. Six phantoms (one untreated, one treated with
      a commercial stent, and four treated with different asymmetric stents) with
      similar morphologies were used for comparison. We calculated time-density curves
      of the aneurysm region and then calculated the peak value (Pk) and washout rate
      (1/tau) after analytical curve fitting. Flow patterns in the angiograms showed
      reduction of vortex flow and slow washout in the dense mesh patch treated
      aneurysms. The meshes reduced Pk down to 21% and 1/tau down to 12% of the values
      for the untreated case. In summary, new asymmetric stents were constructed and
      their evaluation demonstrates that they may be useful in the endovascular
      treatment of aneurysms.

PMID- 21886415
TI  - Naomi's Birth.
AB  - A first-time mother, who is also a nurse, tells the story of her drug-free birth
      at a free-standing birth center.

PMID- 21886416
TI  - Four research findings that will change what we think about perinatal depression.
AB  - Research by health psychologists is changing what we know about perinatal
      depression. In this guest editorial, the author examines depression in pregnant
      and breastfeeding women in light of this recent research and describes four major
      findings that are influencing how we think about depression in new mothers:
      inflammation has an etiologic role in depression, a relationship exists between
      sleep disturbances and depression, breastfeeding protects maternal mental health,
      and all effective treatments for depression are anti-inflammatory interventions.

PMID- 21886417
TI  - Self-efficacy and postpartum depression teaching behaviors of hospital-based
      perinatal nurses.
AB  - Based upon the Self-Efficacy Theory, this study examined the relationship between
      self-efficacy, self-efficacy-related variables, and postpartum depression
      teaching behaviors of hospital-based perinatal nurses. Findings revealed that
      teaching new mothers about postpartum depression is related to a perinatal
      nurse's self-efficacy in postpartum-depression teaching, self-esteem, and the
      following self-efficacy-related variables: social persuasion (supervisor's
      expectations for teaching); mastery (postpartum depression continuing education
      and teaching experience); and vicarious experience (observing other nurses teach
      new mothers about postpartum depression). Teaching new mothers about postpartum
      depression can assist mothers in overcoming barriers to depression treatment.
      Nurse educators and managers play an important role in encouraging postpartum
      depression education for perinatal nurses.

PMID- 21886418
TI  - Evaluation of a practice-development initiative to improve breastfeeding rates.
AB  - The benefits of breastfeeding for infant, mother, family, and community are well
      recognized, and increasing breastfeeding rates is considered an important health
      promotion strategy. Improving breastfeeding knowledge and practice among
      individuals caring for breastfeeding women is considered an important aspect of
      this strategy. The practice-development initiative described in this article
      aimed to improve hospital-based breastfeeding rates through the implementation of
      The Ten Steps to Successful Breastfeeding. The initiative included the
      development and implementation of an education program aimed at changing and
      improving breastfeeding practices. The program was evaluated in three ways:
      changes in breastfeeding rates at hospital discharge; client preparation for
      breastfeeding and satisfaction during the postnatal period; and staff knowledge
      and skills.

PMID- 21886419
TI  - "Going beyond the call of doula": a grounded theory analysis of the diverse roles
      community-based doulas play in the lives of pregnant and parenting adolescent
      mothers.
AB  - This article presents some of the most salient qualitative results from a larger
      program evaluation of pregnant and parenting adolescents who participated in a
      community-based doula program. Using grounded theory analysis, seven problem
      solving strategies emerged that doulas apply in helping pregnant and parenting
      adolescents navigate multiple social and health settings that often serve as
      barriers to positive maternal- and child-health outcomes. The ethnographic
      findings of this study suggest that the doulas provide valuable assistance to
      pregnant and parenting adolescents by addressing social-psychological issues and
      socio-economic disparities. "Diverse role-taking" results in doulas helping
      pregnant adolescents navigate more successfully through fragmented social and
      health service systems that are less supportive of low-income adolescents, who
      are often perceived to be draining scarce resources. The findings have
      implications for the roles of community-based doulas assigned to low-income
      adolescents of color seeking to overcome obstacles and attain better educational
      and economic opportunities.

PMID- 21886420
TI  - Safe and healthy birth: the importance of data.
AB  - In this column, the author reprises recent selections from the Lamaze
      International research blog, Science & Sensibility. Each selection discusses the
      mismatch between data commonly collected at the time of birth and the data needed
      to measure optimal care for physiologic birth. Selections include the importance
      of documenting duration of skin-to-skin contact after birth, the role of
      qualitative research in improving care in the second stage of labor, and pitfalls
      of meta-analyzing data on the safety of planned home birth.

PMID- 21886421
TI  - Five per cent of the time it works 100 per cent of the time: the erroneousness of
      the P value.

PMID- 21886422
TI  - The influence of lower cervical joint pain on range of motion and interpretation
      of the flexion-rotation test.
AB  - OBJECTIVE: The purpose of this study was to investigate the impact of lower
      cervical facet joint pain (CFP) on the flexion-rotation test (FRT). METHODS: A
      single blind, comparative group design was used to investigate whether lower CFP
      influences FRT mobility and examiner interpretation. Twenty-four subjects were
      evaluated, 12 with cervicogenic headache (age 26-63 years) and 12 with lower CFP
      (age 44-62 years), confirmed by therapeutic cervical facet joint intervention. A
      single blinded examiner conducted the FRT, reporting the test state (positive or
      negative) before measuring range of motion using a goniometer. Subjects with
      lower CFP were evaluated by the FRT prior to therapeutic intervention and were
      excluded from analysis if they did not gain complete symptomatic relief following
      the procedure. Only subjects with immediate complete relief were included.
      RESULTS: The average range of unilateral rotation to the limited side during the
      FRT was 26 and 37.5 degrees  for the cervicogenic headache and lower CFP groups
      respectively. The difference between groups was significant (P<0.01). Sensitivity
      and specificity for cervicogenic headache diagnosis was 75 and 92% respectively.
      A receiver operating curve revealed that an experienced examiner using the FRT
      was able to make the correct diagnosis 90% of the time (P<0.01), with a positive
      cut-off value of 32 degrees . DISCUSSION: These findings provide further evidence
      for the clinical utility of the FRT in cervical examination and cervicogenic
      headache diagnosis.

PMID- 21886423
TI  - Thoracic outlet syndrome: a controversial clinical condition. Part 2: non
      surgical and surgical management.
AB  - BACKGROUND: Proper management of thoracic outlet syndrome (TOS) requires an
      understanding of the underlying causes of the disorder. A comprehensive
      examination process, as described in Part 1 of this review, can reveal the bony
      and soft tissue abnormalities and mechanical dysfunctions contributing to an
      individual's TOS symptoms. OBJECTIVE: Part 2 of this review focuses on management
      of TOS. CONCLUSION: The clinician uses clinical examination results to design a
      rehabilitation program that focuses on correcting specific problems that were
      previously identified. Disputed neurogenic TOS is best managed with a trial of
      conservative therapy before surgical treatment options are considered. Cases that
      are resistant to conservative treatment may require surgical intervention. True
      neurogenic TOS may require surgical intervention to relieve compression of the
      neural structures in the thoracic outlet. Surgical management is required for
      cases of vascular TOS because of the potentially serious complications that may
      arise from venous or arterial compromise. Post-operative rehabilitation is
      recommended after surgical decompression to address factors that could lead to a
      reoccurrence of the patient's symptoms.

PMID- 21886424
TI  - Intra-oral myofascial therapy for chronic myogenous temporomandibular disorders:
      a randomized, controlled pilot study.
AB  - OBJECTIVES: Studies investigating the efficacy of intra-oral myofascial therapies
      (IMT) for chronic temporomandibular disorder (TMD) are rare. The objective of
      this randomized, controlled pilot study was to compare the effects of IMT and the
      addition of self-care and education over 6 months on four common TMD outcome
      measures: inter-incisal opening range, jaw pain at rest, jaw pain upon opening,
      and jaw pain upon clenching. PARTICIPANTS: Thirty myogenous TMD participants
      between the ages of 18 and 50 years, experiencing chronic jaw pain of longer than
      3-month duration, were recruited for the present study. INTERVENTION: INCLUDED
      PATIENTS WERE RANDOMIZED INTO ONE OF THREE GROUPS: (1) IMT consisting of two
      treatment interventions per week for 5 weeks; (2) IMT plus 'self-care' involving
      education and exercises; and (3) wait list control. MAIN OUTCOME MEASURES: Range
      of motion findings were measured in millimetres by vernier callipers and pain
      scores were quantified using an 11-point self-reported graded chronic pain scale.
      Measurements were taken at baseline, 6 weeks post-treatment, and 6 months post
      treatment. RESULTS: The results showed statistically significant differences in
      resting, opening, and clenching pain and opening range scores (P<0.05) in both
      treatment groups compared to control at 6 months. No significant differences were
      observed between the two treatment groups during the course of the trial.
      CONCLUSIONS: This study suggests that IMT alone or with the addition of self-care
      may be of some benefit in the management of chronic TMD over the short-medium
      term. A larger scale study over a longer term (1-2 years) may be of further
      value.

PMID- 21886425
TI  - Clinimetrics corner: choosing appropriate study designs for particular questions
      about treatment subgroups.
AB  - BACKGROUND: Many clinicians and researchers believe that there are subgroups of
      people with spinal pain who respond differently to treatment and have different
      prognoses. There has been considerable interest in this topic recently. However,
      problems occur when conclusions about subgroups are made that are inappropriate
      given the randomized controlled trial design used. The research design to choose,
      when developing a study protocol that investigates the effect of treatment
      subgroups, depends on the particular research question. Similarly, the inferences
      that can be drawn from an existing study will vary, depending on the design of
      the trial. OBJECTIVES: This paper discusses the randomized controlled trial
      designs that are suitable to answer particular questions about treatment
      subgroups. It focuses on trial designs that are suitable to answer four
      questions: (1) 'Is the treatment effective in a pre-specified group of
      patients?'; (2) 'Are outcomes of treatment applied using a subgrouping clinical
      reasoning process, better than a control treatment?'; (3) 'Are the outcomes for a
      patient subgroup receiving a particular treatment (compared to a control
      treatment) better than for patients not in the subgroup who receive the same
      treatment?'; and (4) 'Are outcomes for a number of treatments better if those
      treatments are matched to patients in specific subgroups, than if the SAME
      treatments are randomly given to patients?'. Illustrative examples of these
      studies are provided. CONCLUSION: If the clinical usefulness of targeting
      treatments to subgroups of people is to be determined, an important step is a
      shared understanding of what different RCT designs can tell us about subgroups.

PMID- 21886426
TI  - Nucleus pulposus deformation following application of mechanical diagnosis and
      therapy: a single case report with magnetic resonance imaging.
AB  - BACKGROUND: The McKenzie management strategy of mechanical diagnosis and therapy
      (MDT) is commonly used for the assessment and management of spinal problems.
      Within this system, 'derangement syndrome' is the most common classification, for
      which the conceptual model is an intra-discal displacement. However, the
      reduction of an intra-discal displacement by MDT has never been documented. The
      purpose of this study was to compare, using magnetic resonance imaging (MRI), the
      nucleus pulposus (NP) profiles before and after the use of this approach. PATIENT
      CHARACTERISTICS: The patient was a 34-year-old female with a long history of
      right sided low back and buttock pain classified with 'derangement syndrome'.
      EXAMINATION: T2-weighted images of the L4-5 disc at initial assessment were
      compared with that at final assessment 1 month later. Initially, the MRI showed a
      portion of the NP displaced right and posteriorly towards the side of pain, and
      an overall NP position in the coronal plane shifted to the left. INTERVENTION:
      The patient was managed with a 1-month course of the McKenzie management strategy
      treatment. OUTCOMES: One month later, the displaced portion of the NP was no
      longer present and the left-shifted NP was centrally located. DISCUSSION: These
      intervertebral disc changes coincided with centralization and abolition of
      symptoms. This case may support the conceptual model of MDT.

PMID- 21886427
TI  - Differential diagnosis and management of a patient with peripheral vestibular and
      central nervous system disorders: a case study.
AB  - BACKGROUND: Clinical examination and management of patients with meningiomas is
      primarily dependent upon appropriate diagnosis of tumor type and surgical
      intervention. Physical therapists should be able to identify patients presenting
      with signs and symptoms suggestive of potential central nervous system (CNS)
      disorders and refer the patient appropriately. PATIENT CHARACTERISTICS: In this
      case report, a 52-year-old female was referred to physical therapy after 18
      months of unresolved dizziness. EXAMINATION: Oculomotor examination revealed
      evidence of peripheral vestibular and potential CNS disorders. The physical
      therapist referred the patient to a physician who ordered magnetic resonance
      imaging (MRI). INTERVENTION: The patient received five physical therapy sessions
      while waiting for the MRI which revealed a meningioma. The meningioma was
      surgically removed and the patient was subsequently relieved of all symptoms.
      OUTCOMES: Despite the presence of the meningioma, the patient reported improved
      stability during work-related activities and decreased dizziness as a result of
      physical therapy intervention pre-operatively. DISCUSSION: This case report
      emphasizes the importance of a physical therapists ability to perform and
      interpret an oculomotor examination in a patient presenting with signs consistent
      with peripheral vestibular and CNS disorders. It also demonstrates the role of
      physical therapy in collaboration with physicians in order to provide appropriate
      patient care management.

PMID- 21886428
TI  - The ability of a sustained within-session finding of pain reduction during
      traction to dictate improved outcomes from a manual therapy approach on patients
      with osteoarthritis of the hip.
AB  - OBJECTIVES: THE OBJECTIVES OF THIS STUDY WERE TO: (1) determine the association
      of a within-session finding after traction of the hip with self-report of well
      being, pain, and self-report of function at 9 weeks; and (2) to determine if the
      interactions between the within-session finding and the outcome measure are
      different between groups of patients with hip OA who receive and who do not
      receive manual therapy. METHODS: Data were retrospectively analysed in 70
      subjects who were part of a randomized control trial. Correlation analyses of
      within-session findings from the initial visit after traction of a concordantly
      painful hip were compared to self-report measures for function, pain, and well
      being at 9 weeks. A comparison of slope coefficients between manual therapy and
      non-manual therapy groups was performed to determine the interactive aspects of
      the within-session finding. RESULTS: Although the correlations for the manual
      therapy group were higher than for the supervised neglect group, none of the
      correlational analyses for both groups was strong or significant. Significant
      differences in the slope coefficients for well-being and pain were found,
      suggesting that the interactions between the within-session findings and the
      targeted outcomes were different in the manual therapy group versus supervised
      neglect group. DISCUSSION: These findings suggest that within-session findings
      during the initial evaluation are not strongly related to a positive outcome
      after manual therapy, although the interaction of the finding of a within-session
      change and the use of manual therapy is more compelling than the finding in a
      sample of patients who did not receive manual therapy.

PMID- 21886429
TI  - Palladium(0) catalyzed 2,2'-bipyrrole syntheses.
AB  - Several 2-iodopyrroles are used in Pd(0) catalyzed homocoupling reactions at room
      temperature in the presence of water to efficiently synthesize 2,2'-bipyrroles.
      These 2,2'-bipyrroles are strongly luminous materials and have high fluorescence
      quantum yields.

PMID- 21886430
TI  - Co-occurring amphetamine use and associated medical and psychiatric comorbidity
      among opioid-dependent adults: results from the Clinical Trials Network.
AB  - BACKGROUND: In response to the rising rate of treatment admissions related to
      illicit use of amphetamines (eg, methamphetamine), we examined the prevalence of
      amphetamine use among treatment-seeking, opioid-dependent adults, explored
      whether amphetamine users were as likely as nonamphetamine users to enroll in
      opioid-dependence treatment trials, and determined whether amphetamine users
      manifested greater levels of medical and psychiatric comorbidity than nonusers. 
      METHODS: The sample included 1257 opioid-dependent adults screened for
      participation in three-multisite studies of the National Drug Abuse Treatment
      Clinical Trials Network (CTN001-003), which studied the effectiveness of
      buprenorphine for opioid detoxification under varying treatment conditions.
      Patients were recruited from 23 addiction treatment programs across the US.
      Medical and psychiatric comorbidity were examined by past-month amphetamine use
      (current vs former) and route of administration. Five mutually exclusive groups
      were examined, ie, nonusers, current amphetamine injectors, current amphetamine
      noninjectors, former amphetamine injectors, and former amphetamine noninjectors. 
      RESULTS: Of the sample (n = 1257), 22.3% had a history of regular amphetamine
      use. Of the 280 amphetamine users, 30.3% reported injection as their primary
      route. Amphetamine users were more likely than nonusers to be white and use more
      substances. Amphetamine users were as likely as non-users to enroll in treatment
      trials. Bivariate analyses indicated elevated rates of psychiatric problems
      (depression, anxiety, hallucinations, cognitive impairment, violence, suicidal
      thoughts/attempts) and medical illnesses (dermatological, hepatic,
      cardiovascular, respiratory, neurological, seizure, allergy conditions) among
      amphetamine users. After adjusting for demographic variables and lifetime use of
      other substances: current amphetamine users and former injectors showed an
      increased likelihood of having medical illnesses and hospitalizations; current
      injectors had elevated odds of suicidal thoughts or attempts; current
      noninjectors exhibited elevated odds of anxiety, cognitive impairment, and
      violent behaviors; and former noninjectors had increased odds of depression. 
      CONCLUSION: Treatment-seeking, amphetamine-using, opioid-dependent adults
      manifest greater levels of medical and psychiatric morbidity than treatment
      seeking, opioid-dependent adults who have not used amphetamines, indicating a
      greater need for intensive clinical management.

PMID- 21886431
TI  - Histological assessment of tangentially excised burn eschars.
AB  - BACKGROUND: The burn eschar serves as a medium for bacterial growth and a source
      of local and systemic infection. To prevent or minimize these complications, it
      is important to debride the eschar as early as possible. OBJECTIVE: To identify
      the presence of viable skin within the excisions by examining tangentially
      excised burn eschars. METHODS: A total of 146 samples of burned human tissue were
      removed during 54 routine sharp tangential excision procedures (using
      dermatomes). The samples were histologically examined to identify the relative
      thickness of the dead, intermediate and viable layers. RESULTS: The mean (+/- SD)
      thickness of the excised samples was 1.7+/-1.1 mm. The sacrificed viable tissue
      (mean thickness 0.7+/-0.8 mm) occupied 41.2% of the entire thickness of the
      excision. In 32 biopsies (21.8%; 95% CI 16.0 to 29.3), the excision did not reach
      viable skin. Only eight biopsies (5.4%; 95% CI 2.8 to 10.1) contained all of the
      necrotic tissue without removing viable tissue. CONCLUSIONS: The thickness of a
      single tangentially excised layer of eschar is not much greater than the actual
      thickness of the entire skin and often contains viable tissue. Because surgical
      debridement is insufficiently selective, more selective means of debriding burn
      eschars should be explored.

PMID- 21886432
TI  - Postoperative management of carpometacarpal joint fracture dislocation of the
      hand: A case report.
AB  - Injury to the carpometacarpal joints is rare. The strong ligamentous attachments
      and carpal bone alignment readily resist displacement. To the authors' knowledge,
      there are no studies evaluating postoperative recovery regimens of
      carpometacarpal fracture dislocations. The present study describes a
      postoperative hand therapy regimen that used a novel carpometacarpal brace
      permitting early mobilization.

PMID- 21886434
TI  - Reflections of a country plastic surgeon.

PMID- 21886433
TI  - Invasive squamous cell carcinoma of the hand in a patient with Kindler syndrome:
      Case report and literature review.
AB  - Kindler syndrome is a rare, autosomal, recessive genodermatosis characterized by
      trauma-induced acral blisters in infancy and childhood, photosensitivity and
      progressive poikiloderma. Very few cases in the literature report an association
      with squamous cell carcinoma, even though it is a very well-known, long-term
      complication. A case involving a 23-year-old woman with a history of Kindler
      syndrome who was admitted to the department of plastic surgery (Sherbrooke
      University, Sherbrooke, Quebec) with an extensive ulcerated squamous cell
      carcinoma of the right hand is presented. A local excision of the tumour was
      initially performed, but positive margins and clinically palpable axillary
      lymphadenopathy over the course of hospitalization necessitated below-elbow
      amputation and lymph node dissection. To the authors' knowledge, this is the
      second reported case of aggressive metastatic squamous cell carcinoma of the hand
      in a patient with Kindler syndrome.

PMID- 21886435
TI  - 'Universal retraction suture' for the overprojecting nasal tip.
AB  - Achieving a proper nasal tip projection is a crucial element of a successful
      rhinoplasty. A large number of correction methods and manoeuvres have been
      proposed in the medical literature as solutions for the prominent nasal tip, thus
      complicating the surgeon's strife to choose the ideal plan of action. In the
      present article, a single straight-forward technique, christened the 'universal
      retraction suture', is suggested to tackle the overprojecting tip in a
      simplified, controlled and efficient fashion.

PMID- 21886436
TI  - Factors affecting surgical wait times for breast reconstruction.
AB  - OBJECTIVE: To examine factors that affect wait times for women seeking breast
      reconstruction at a Canadian academic centre. METHODS: A retrospective audit of
      57 women seeking breast reconstruction over a three-year period was completed.
      Comparisons of wait times were made considering the surgical pathology, timing of
      reconstruction (immediate versus delayed), urgency of pathology, method of
      reconstruction (implant versus autologous) and the number of surgeons involved.
      Specifically, the wait times from referral to specialist consultation,
      consultation to surgery, and referral to surgery were examined. RESULTS: WOMEN
      WITH ACTIVE CANCER (DUCTAL CARCINOMA IN SITU: 43 days, invasive cancer: 40 days)
      had shorter wait times compared with those who had no active cancer (benign/high
      risk: 242 days, previously treated cancer: 343 days) (P<0.05). Women seeking
      delayed reconstruction had longer wait times (359 days) from referral to surgery
      than women seeking immediate reconstruction (98 days) (P<0.0001). Women seeking
      reconstruction at the time of mastectomy, with benign/high-risk disease, waited
      longer (242 days) than those with ductal carcinoma in situ (43 days) or invasive
      cancer (40 days) (P<0.001). Wait times for autologous free tissue transfer (213
      days) were not significantly longer compared with implant reconstruction (116
      days) (P=0.27). Women with acute cancer experienced similar wait times for
      implant reconstruction (44 days) as for a free tissue transfer (56 days)
      (P=0.46). Women with no acute cancer had similar wait times for implant (239
      days) as free tissue transfer (369 days) (P=0.25). Patients requiring only
      plastic surgeons involved in the reconstructive effort waited longer (one
      surgeon: 299 days, two surgeons: 550 days) than patients requiring either two
      plastic surgeons and one general surgeon (130 days) or one plastic surgeon and
      one general surgeon (82 days) (P<0.05). Although more coordination is required
      with three surgeons, this is frequently associated with a diagnosis of acute
      cancer and, therefore, wait times are shorter.

PMID- 21886438
TI  - Canadian Society for Aesthetic (Cosmetic) Plastic Surgery/Societe canadienne de
      chirurgie plastique esthetique: Abstracts presented at the 37th Annual Meeting
      October 1 and 2, 2010.

PMID- 21886437
TI  - Total scalp avulsion with microvascular reanastomosis: A case report and
      literature review.
AB  - Total scalp avulsion is a rare but potentially devastating injury that when
      treated (following a few basic principles) can have very good reconstructive
      results. The present article reviews the current literature and describes the
      steps involved in the successful replantation of a complete avulsed scalp of a 33
      year-old woman. To the authors' knowledge, the present case regarding
      replantation of a complete avulsed scalp using only a single artery is the first
      to be described in the Canadian literature.

PMID- 21886439
TI  - Treatment cost effectiveness in acute otitis media: A watch-and-wait approach
      versus amoxicillin.
AB  - In Canada, antimicrobial treatment is the most common approach for acute otitis
      media. The aim of the present study was to compare the cost effectiveness of
      treatment with amoxicillin versus a watch-and-wait approach (WAIT) within a
      Canadian pediatric setting. Four hundred eighty-eight children, six months to
      five years of age, who participated in a randomized controlled trial were
      included in the study. The average medication costs per patient were higher for
      the amoxicillin group ($17.26) than for the WAIT group ($4.33). However, both
      health care ($148.44 versus $162.48) and patient costs ($23.50 versus $31.87)
      were greater for the WAIT group. The mean cost of treatment for the amoxicillin
      group was $189.20, compared with $198.68 for the WAIT group. Amoxicillin may be
      cost effective in treating children with acute otitis media. The potential
      development of antimicrobial resistance was not addressed in the present study.

PMID- 21886440
TI  - Has the Alberta daily physical activity initiative been successfully implemented
      in Calgary schools?
AB  - INTRODUCTION: In September 2005, the Alberta government introduced the daily
      physical activity (DPA) initiative, which requires that students from grades 1 to
      9 be physically active in school for a minimum of 30 min per day. OBJECTIVE: To
      obtain information on whether and how the DPA initiative has been implemented in
      Calgary schools. METHODS: Information was obtained through a descriptive survey.
      Principals and vice-principals from elementary schools participated in an
      interview, in which they were asked questions about the DPA initiative, their
      definition of physical activity, the types of activities that fulfilled the DPA
      requirement, and barriers to increasing physical activity and physical education.
      RESULTS: 98.2% of respondents reported being aware of the DPA initiative; 100% of
      respondents reported it being successfully implemented. The leading responses to
      the question, "How do you define physical activity?" were "moving/movement"
      (43.5%), "increasing the heart rate" (32.7%) and "being active" (29%). 78.2% of
      participants responded that physical education was the only type of activity that
      fulfilled the DPA requirement; the other participants reported that recess,
      intramurals and DPA periods organized by the teacher also counted. 69.1% and
      61.1% of respondents, respectively, stated that there were barriers to increasing
      physical education and physical activity. A lack of time in the curriculum, a
      lack of space and a lack of funding were the most frequently reported barriers.
      CONCLUSION: According to principal and vice-principal reports, the DPA initiative
      has been successfully implemented in elementary schools in Calgary. This suggests
      that government initiatives directed at increasing physical activity at school
      could result in increasing the actual amount of physical activity that children
      participate in. However, prospective longitudinal research directly measuring the
      amount of physical activity that children engage in is needed to directly assess
      the impact of such initiatives.

PMID- 21886441
TI  - Looking back, looking forward.

PMID- 21886442
TI  - Adrenal suppression: An under-recognized complication of a common therapy.

PMID- 21886443
TI  - Case 2: Making a diagnosis: Lest we forget the family.

PMID- 21886444
TI  - Case 1: Vesicular rash in an infant.

PMID- 21886445
TI  - Childhood overweight and obesity management: A national perspective of primary
      health care providers' views, practices, perceived barriers and needs.
AB  - BACKGROUND: Obesity and overweight in children are an escalating problem in
      Canada and worldwide. Currently, little is known about the manner in which
      primary health care providers are responding to Canada's obesity epidemic.
      OBJECTIVE: To determine the views, practices, challenges/barriers, and needs of a
      national sample of family physicians (FPs) and community paediatricians (CPs)
      with respect to paediatric obesity identification and management. METHODS: A self
      administered questionnaire was mailed to a random sample of 1200 FPs and 1200 CPs
      across Canada between 2005 and 2006. RESULTS: A total of 464 FPs and 396 CPs
      participated. The majority of practitioners viewed paediatric obesity as an
      'important'/'very important' issue. Although the majority reported providing
      dietary (more than 85%) and exercise (98%) advice to their overweight/obese
      patients, practitioners' perceived success rate in treating paediatric obesity
      was limited (less than 22%). Approximately 30% of FPs and 60% of CPs (P<0.05)
      used the recommended method to identify paediatric obesity. At least 50% of
      practitioners indicated that too few government-funded dietitians, a lack of
      success in controlling paediatric patients' weight, time constraints and limited
      training were key barriers to their success. To support efforts to identify or
      manage paediatric obesity, practitioners identified the need for office tools,
      patient educational materials and system-level changes. DISCUSSION: Canadian
      primary health care providers are not adequately equipped to deal with the
      paediatric obesity epidemic. Effective assessment tools and treatment resources,
      dissemination of clinical practice guidelines, enhanced undergraduate medical
      education and postgraduate continuing medical education, and system-level changes
      are urgently needed to address this health problem.

PMID- 21886446
TI  - Which method of breastfeeding supplementation is best? The beliefs and practices
      of paediatricians and nurses.
AB  - The aims of the present study were to assess the practices of breastfeeding
      supplementation methods, and to explore the opinions and beliefs of health
      professionals with regard to breastfeeding supplementation methods and the nipple
      confusion phenomenon. The study was cross-sectional in design, and participants
      were recruited from five hospitals in Toronto, Ontario. All of the nurses and
      attending paediatricians in postpartum floors and level II nurseries were invited
      to participate in the study. A total of 87 nurses and 16 paediatricians completed
      the survey questionnaire. Bottle feeding was the most common breastfeeding
      supplementation method used in the nurseries followed by cup feeding. Only 15.0%
      of the level II nurses agreed that frequent bottle feeds lead to the nipple
      confusion phenomenon, compared with 44.4% of the postpartum nurses and 56.2% of
      the paediatricians. Findings demonstrated considerable variation in the practices
      and beliefs surrounding supplementation methods. A randomized controlled trial
      comparing the safety, efficiency and subsequent breastfeeding rates of different
      breastfeeding supplementation methods is warranted.

PMID- 21886447
TI  - Maternal relationship style, paediatric health care use and infant health.
AB  - OBJECTIVE: The aim of the current exploratory study was to examine the
      relationships between maternal relationship style, paediatric health care use and
      infant health variables in a sample of middle-class and ethnically diverse mother
      infant dyads. METHODS: An initial cross-sectional cohort study obtained
      demographic and self-report data on mothers' relationship styles. As an extension
      of the original study, infants' patient files were reviewed for the year
      following initial recruitment to obtain data regarding the use of paediatric
      health care services and infant health. The final sample included 64 mothers and
      their infants. RESULTS: Correlational analyses revealed that mothers' higher
      endorsement of a dismissive relationship style were associated with fewer acute
      care visits and fewer reported infant illnesses. CONCLUSIONS: Compared with other
      relationship styles, mothers who highly endorsed a dismissive relationship style
      tended to use fewer acute paediatric health care services and reported fewer
      infant health problems. However, further longitudinal research is needed to
      clarify these relationships.

PMID- 21886448
TI  - Otitis media incidence and risk factors in a population-based birth cohort.
AB  - BACKGROUND: Otitis media is the main reason young children receive antibiotics
      and is the leading reason for physician visits. OBJECTIVE: To characterize the
      incidence, recurrence and risk factors for otitis media in a population-based
      birth cohort. METHODS: All children born in southwestern British Columbia during
      1999 to 2000 were followed until the age of three years. Otitis media was defined
      using The International Classification of Diseases, Ninth Revision coding of
      physician visits, and linked with antibiotic prescription data. Information on
      sex, birth weight, gestational age, Aboriginal status, maternal age, older
      siblings, maternal smoking during pregnancy, breastfeeding initiation,
      neighbourhood income, female education and rural residence were obtained from
      vital statistics, birth hospitalizations, perinatal registry and census data.
      RESULTS: Complete risk factor information was available for 50,474 children (86%
      of all births). Nearly one-half of the children (48.6%) had one or more physician
      visits for otitis media during follow-up, and 3952 children (7.8%) met the
      definition for recurrent otitis media. Of the children with at least three visits
      during follow-up (n=7571), 73% had their initial visit during the first year of
      life. Aboriginal status, maternal age younger than 20 years, male sex and older
      siblings were the strongest risk factors identified in the adjusted conditional
      logistic regression models. DISCUSSION: The present study established a
      population-based birth cohort by linking multiple administrative databases to
      characterize the incidence of and risk factors for otitis media. Although the
      incidence of otitis media is generally low in southwestern British Columbia,
      important risk factors continue to be young maternal age, mothers who smoke
      during pregnancy and children with Aboriginal ancestry.

PMID- 21886449
TI  - Inhalant abuse.
AB  - Inhalant abuse - also known as volatile substance abuse, solvent abuse, sniffing,
      huffing and bagging - is the deliberate inhalation of a volatile substance to
      achieve an altered mental state. Inhalant abuse is a worldwide problem that is
      especially common in individuals from minority and marginalized populations, and
      is strongly correlated with the social determinants of health. It often affects
      younger children, compared with other forms of substance abuse, and crosses
      social and ethnic boundaries. Inhalants are pharmacologically diverse products
      that are selected for their low price, legal and widespread availability, and
      ability to rapidly induce euphoria. Chronic abuse is associated with serious and
      often irreversible effects. Widespread screening and early referrals to treatment
      programs have resulted in significant improvements in the mental, physical and
      social conditions of those affected. The present statement reviews critical
      aspects of inhalant abuse, highlighting new information and data that pertain to
      Aboriginal children and youth, and provides recommendations for treatment and
      prevention.

PMID- 21886451
TI  - Genetic and epigenetic alterations in pancreatic carcinogenesis.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers
      worldwide. Despite significant progresses in the last decades, the origin of this
      cancer remains unclear and no efficient therapy exists. PDAC does not arise de
      novo: three remarkable different types of pancreatic lesions can evolve towards
      pancreatic cancer. These precursor lesions include: Pancreatic intraepithelial
      neoplasia (PanIN) that are microscopic lesions of the pancreas, Intraductal
      Papillary Mucinous Neoplasms (IPMN) and Mucinous Cystic Neoplasms (MCN) that are
      both macroscopic lesions. However, the cellular origin of these lesions is still
      a matter of debate. Classically, neoplasm initiation or progression is driven by
      several genetic and epigenetic alterations. The aim of this review is to assemble
      the current information on genetic mutations and epigenetic disorders that affect
      genes during pancreatic carcinogenesis. We will further discuss the interest of
      the genetic and epigenetic alterations for the diagnosis and prognosis of PDAC.
      Large genetic alterations (chromosomal deletion/amplification) and single point
      mutations are well described for carcinogenesis inducers. Mutations classically
      occur within key regions of the genome. Consequences are various and include
      activation of mitogenic pathways or silencing of apoptotic processes. Alterations
      of K-RAS, P16 and DPC4 genes are frequently observed in PDAC samples and have
      been described to arise gradually during carcinogenesis. DNA methylation is an
      epigenetic process involved in imprinting and X chromosome inactivation.
      Alteration of DNA methylation patterns leads to deregulation of gene expression,
      in the absence of mutation. Both genetic and epigenetic events influence genes
      and non-coding RNA expression, with dramatic effects on proliferation, survival
      and invasion. Besides improvement in our fundamental understanding of PDAC
      development, highlighting the molecular alterations that occur in pancreatic
      carcinogenesis could provide new clinical tools for early diagnosis of PDAC and
      the molecular basis for the development of new effective therapies.

PMID- 21886452
TI  - Carcinoma of the Lower Uterine Segment (LUS): Clinicopathological Characteristics
      and Association with Lynch Syndrome.
AB  - Endometrial cancer arises from the uterine body and fundus in many cases, but can
      also originate from the lower region of the uterine body through the upper region
      of the cervix. Such tumors are referred to as carcinoma of the lower uterine
      segment (LUS) or isthmus, and account for 3-6.3% of all cases of endometrial
      cancer. This relatively low incidence has permitted performance of only small
      scale studies, but the clinical and pathological characteristics of carcinoma of
      the LUS in all these reports have differed from those of other endometrial
      cancers. Generally, endometrial cancer is classified into estrogen-dependent
      endometrioid adenocarcinoma (designated as type I), and non-endometrioid types
      that are less associated with estrogen and include poorly differentiated
      adenocarcinoma (type II). In some reports, carcinoma of the LUS has been found to
      have type II characteristics. Carcinoma of the LUS has also been associated with
      Lynch syndrome, a hereditary disease with frequent development of colorectal,
      endometrial, and ovarian cancers. Lynch syndrome is thought to be induced by
      mismatch repair gene mutation. The frequency of Lynch syndrome in cases of
      general endometrial cancer is 1-2%. In contrast, the frequency in patients with
      carcinoma of the LUS is much higher, with up to 29% of cases diagnosable with
      Lynch syndrome and a high frequency of hMSH2 mutation found in one study. This
      suggests that further investigation of the clinical and pathological
      characteristics of carcinoma of the LUS and the association with Lynch syndrome
      is required through performance of a large-scale survey.

PMID- 21886450
TI  - Perspectives on Systematic Analyses of Gene Function in Arabidopsis thaliana: New
      Tools, Topics and Trends.
AB  - Since the sequencing of the nuclear genome of Arabidopsis thaliana ten years ago,
      various large-scale analyses of gene function have been performed in this model
      species. In particular, the availability of collections of lines harbouring
      random T-DNA or transposon insertions, which include mutants for almost all of
      the ~27,000 A. thaliana genes, has been crucial for the success of forward and
      reverse genetic approaches. In the foreseeable future, genome-wide phenotypic
      data from mutant analyses will become available for Arabidopsis, and will
      stimulate a flood of novel in-depth gene-function analyses. In this review, we
      consider the present status of resources and concepts for systematic studies of
      gene function in A. thaliana. Current perspectives on the utility of loss-of
      function and gain-of-function mutants will be discussed in light of the genetic
      and functional redundancy of many A. thaliana genes.

PMID- 21886453
TI  - Engineering cold stress tolerance in crop plants.
AB  - Plants respond with changes in their pattern of gene expression and protein
      products when exposed to low temperatures. Thus ability to adapt has an impact on
      the distribution and survival of the plant, and on crop yields. Many species of
      tropical or subtropical origin are injured or killed by non-freezing low
      temperatures, and exhibit various symptoms of chilling injury such as chlorosis,
      necrosis, or growth retardation. In contrast, chilling tolerant species are able
      to grow at such cold temperatures. Conventional breeding methods have met with
      limited success in improving the cold tolerance of important crop plants
      involving inter-specific or inter-generic hybridization. Recent studies involving
      full genome profiling/ sequencing, mutational and transgenic plant analyses, have
      provided a deep insight of the complex transcriptional mechanism that operates
      under cold stress. The alterations in expression of genes in response to cold
      temperatures are followed by increases in the levels of hundreds of metabolites,
      some of which are known to have protective effects against the damaging effects
      of cold stress. Various low temperature inducible genes have been isolated from
      plants. Most appear to be involved in tolerance to cold stress and the expression
      of some of them is regulated by C-repeat binding factor/ dehydration-responsive
      element binding (CBF/DREB1) transcription factors. Numerous physiological and
      molecular changes occur during cold acclimation which reveals that the cold
      resistance is more complex than perceived and involves more than one pathway. The
      findings summarized in this review have shown potential practical applications
      for breeding cold tolerance in crop and horticultural plants suitable to
      temperate geographical locations.

PMID- 21886454
TI  - LHON: Mitochondrial Mutations and More.
AB  - Leber's hereditary optic neuropathy (LHON) is a mitochondrial disorder leading to
      severe visual impairment or even blindness by death of retinal ganglion cells
      (RGCs). The primary cause of the disease is usually a mutation of the
      mitochondrial genome (mtDNA) causing a single amino acid exchange in one of the
      mtDNA-encoded subunits of NADH:ubiquinone oxidoreductase, the first complex of
      the electron transport chain. It was thus obvious to accuse neuronal energy
      depletion as the most probable mediator of neuronal death. The group of Valerio
      Carelli and other authors have nicely shown that energy depletion shapes the cell
      fate in a LHON cybrid cell model. However, the cybrids used were osteosarcoma
      cells, which do not fully model neuronal energy metabolism. Although complex I
      mutations may cause oxidative stress, a potential pathogenetic role of the latter
      was less taken into focus. The hypothesis of bioenergetic failure does not
      provide a simple explanation for the relatively late disease onset and for the
      incomplete penetrance, which differs remarkably between genders. It is assumed
      that other genetic and environmental factors are needed in addition to the
      'primary LHON mutations' to elicit RGC death. Relevant nuclear modifier genes
      have not been identified so far. The review discusses the unresolved problems of
      a pathogenetic hypothesis based on ATP decline and/or ROS-induced apoptosis in
      RGCs.

PMID- 21886456
TI  - ?
AB  - Esse artigo descreve como jovens religiosos e autoridades religiosas de sua
      comunidade compreendem a sexualidade, considerando suas experiencias pessoais e
      como membros de comunidades religiosas. A analise pretende contribuir para que
      politicas publicas dedicadas a promocao da saude sexual da juventude considerem a
      religiosidade, no contexto de um estado laico e da promocao do direito a
      prevencao. Foram realizadas 26 entrevistas abertas e semidirigidas em diferentes
      comunidades da regiao metropolitana da cidade de Sao Paulo (comunidades
      catolicas, da umbanda, do candomble e de diferentes denominacoes evangelicas)
      sobre iniciacao sexual, casamento, gravidez, contracepcao e prevencao das
      DST/Aids, homossexualidade, aborto e direitos humanos. Observou-se como jovens e
      autoridades religiosas convivem com a tensao entre tradicao e modernidade e os
      distintos discursos sobre a sexualidade. Como sujeitos religiosos (do discurso
      religioso) e sujeitos sexuais (de discursos sobre sexualidade), devem ser
      incorporados pelos programas como sujeitos de direito nos termos de sua
      religiosidade.

PMID- 21886455
TI  - Structural genomics: correlation blocks, population structure, and genome
      architecture.
AB  - An integration of the pattern of genome-wide inter-site associations with
      evolutionary forces is important for gaining insights into the genomic evolution
      in natural or artificial populations. Here, we assess the inter-site correlation
      blocks and their distributions along chromosomes. A correlation block is broadly
      termed as the DNA segment within which strong correlations exist between genetic
      diversities at any two sites. We bring together the population genetic structure
      and the genomic diversity structure that have been independently built on
      different scales and synthesize the existing theories and methods for
      characterizing genomic structure at the population level. We discuss how
      population structure could shape correlation blocks and their patterns within and
      between populations. Effects of evolutionary forces (selection, migration,
      genetic drift, and mutation) on the pattern of genome-wide correlation blocks are
      discussed. In eukaryote organisms, we briefly discuss the associations between
      the pattern of correlation blocks and genome assembly features in eukaryote
      organisms, including the impacts of multigene family, the perturbation of
      transposable elements, and the repetitive nongenic sequences and GC-rich
      isochores. Our reviews suggest that the observable pattern of correlation blocks
      can refine our understanding of the ecological and evolutionary processes
      underlying the genomic evolution at the population level.

PMID- 21886457
TI  - Development of angle-resolved low coherence interferometry for clinical detection
      of dysplasia.
AB  - This review covers the development of angle-resolved low coherence interferometry
      (a/LCI) from initial development through clinical application. In the first
      applications, the approach used a time-domain interferometry scheme and was
      validated using animal models of carcinogenesis to assess the feasibility of
      detecting dysplasia in situ. Further development of the approach led to Fourier
      domain interferometry schemes with higher throughput and endoscope-compatible
      probes to enable clinical application. These later implementations have been
      applied to clinical studies of dysplasia in Barrett's esophagus tissues, a
      metaplastic tissue type that is associated with an increased risk of esophageal
      adenocarcinoma. As an alternative to systematic biopsy, the a/LCI approach offers
      high sensitivity and specificity for detecting dysplasia in these tissues while
      avoiding the need for tissue removal or exogenous contrast agents. Here, the
      various implementations of a/LCI are discussed and the results of the preliminary
      animal experiments and ex vivo human tissue studies are reviewed. A review of a
      recent in vivo clinical study is also presented.

PMID- 21886459
TI  - Relative contributions of passband and filter skirts to the intelligibility of
      bandpass speech: Some effects of context and amplitude.
AB  - Warren et al. (1995) reported over 90% intelligibility for everyday sentences
      reduced to a 1/3-octave band (center frequency 1,500 Hz, slopes 100 dB/octave,
      slow-rms peak levels 75 dB). To investigate the basis of this high
      intelligibility, Warren and Bashford (1999) partitioned the sentences.
      Surprisingly, the rectangular 1/3-octave passband had only 24% intelligibility,
      whereas the filter skirts separated by a 1/3-octave notch had an intelligibility
      of 83%, despite their severe spectral tilts. Experiment 1 of the present study
      substituted monosyllabic words for sentences. Wholeband intelligibility was 26%,
      the passband 4%, and the filter skirts 16%. Experiment 2 measured intelligibility
      for 1/3-octave sentences having peak levels ranging from 85 down to 35 dB. Whole
      band intelligibility ranged from 90% to 68%, and the filter skirt pairs had from
      two to four times the passband's intelligibility (which did not vary
      significantly with level). Hence, steep (100 dB/octave) filter skirts make the
      dominant contribution to intelligibility of nominally 1/3-octave speech across a
      wide range of presentation levels.

PMID- 21886460
TI  - Scott R. Steele, m.d.

PMID- 21886461
TI  - Enterocutaneous fistulas.

PMID- 21886458
TI  - Androgen receptor signaling in prostate cancer development and progression.
AB  - The androgen receptor (AR) signaling axis plays a critical role in the
      development, function and homeostasis of the prostate. The classical action of AR
      is to regulate gene transcriptional processes via AR nuclear translocation,
      binding to androgen response elements on target genes and recruitment of, or
      crosstalk with, transcription factors. Prostate cancer initiation and progression
      is also uniquely dependent on AR. Androgen deprivation therapy remains the
      standard of care for treatment of advanced prostate cancer. Despite an initial
      favorable response, almost all patients invariably progress to a more aggressive,
      castrate-resistant phenotype. Considerable evidence now supports the concept that
      development of castrate-resistant prostate cancer (CRPC) is causally related to
      continued transactivation of AR. Understanding the critical events and
      complexities of AR signaling in the progression to CRPC is essential in
      developing successful future therapies. This review provides a synopsis of AR
      structure and signaling in prostate cancer progression, with a special focus on
      recent findings on the role of AR in CRPC. Clinical implications of these
      findings and potential directions for future research are also outlined.

PMID- 21886462
TI  - Historical perspectives in the care of patients with enterocutaneous fistula.
AB  - Evidence can be found throughout surgical history of how devastating an
      enterocutaneous fistula (ECF) can be for both patient and surgeon. From
      antiquity, this complication of abdominal surgery, malignancy, radiation, trauma,
      or inflammatory processes has been a significant challenge to surgeons due to
      high associated mortality and significant morbidity. An ECF causes dehydration,
      malnutrition, skin excoriation, and sepsis, and has profound psychological
      effects on the patient. Recent mortality rates of patients suffering an ECF
      approach 20%. The authors illustrate the history of management of patients with
      ECF and discuss advances in perioperative care including parasurgical care,
      nutrition, wound care, and the history of surgical techniques.

PMID- 21886463
TI  - Metabolic support of the enterocutaneous fistula patient.
AB  - Enterocutaneous fistula (ECF) is a challenging clinical problem with many
      etiologies; however, the most common cause is iatrogenic, complicating abdominal
      surgery. Advances in the overall care of the ECF patient have resulted in
      dramatic reductions in morbidity and mortality over the last five decades. A
      structured approach to the management of ECF has been shown to result in improved
      outcomes. Initial physiologic stabilization of the postoperative patient, focused
      on hemodynamic and fluid support as well as aggressive sepsis control are the
      critical initial maneuvers. Subsequent optimization of nutrition and wound care
      allows the patient to regain a positive nitrogen balance, and allow for healing.
      Judicious use of antimotility agents as well as advanced wound care techniques
      helps to maximize healing as well as quality of life, and prepare patients for
      subsequent definitive surgery.

PMID- 21886465
TI  - Enterostomal therapy and wound care of the enterocutaneous fistula patient.
AB  - Enterocutaneous fistulas represent a challenging situation with respect to wound
      care and stoma therapy. An understanding of the principles of wound care and the
      various techniques and materials that are available is of vital importance to
      enhance patient comfort and recovery as well as facilitate fistula healing. Skin
      barriers, adhesives, dressings, pouches, and negative pressure dressings are all
      materials that are available in the armamentarium of the enterostomal therapist.
      Proper utilization of these items and appropriate modifications to their
      application requires an intimate knowledge of the characteristics of the fistula
      being treated. Wound care management is a key element in the overall care and
      healing of the enterocutaneous fistula.

PMID- 21886464
TI  - Radiographic and endoscopic diagnosis and treatment of enterocutaneous fistulas.
AB  - The management of enterocutaneous fistulas continues to be a challenging
      postoperative complication. Understanding the anatomy of the fistula optimizes
      its evaluation and management. Diagnostic radiology has always played an
      important role in this task. The use of plain radiography with contrasted studies
      and fistulograms is well documented in the earliest investigations of fistulas
      and they continue to be helpful techniques. The imaging techniques have evolved
      rapidly over the past 15 years with the introduction of cross-sectional imaging,
      ultrasound and endoscopy. The purpose of this chapter is to review both the
      diagnostic and therapeutic roles of fistulograms, small bowel follow-through,
      computed tomography, magnetic resonance imaging, ultrasound, and endoscopy in the
      setting of acquired enterocutaneous fistulas.

PMID- 21886466
TI  - Enterocutaneous fistula: medical and surgical management including patients with
      Crohn's disease.
AB  - Patients with inflammatory bowel disease (IBD) and especially Crohn's disease can
      be challenging for even the most seasoned of surgeons. Development of an
      enterocutaneous fistula (ECF) in these patients further adds a level of
      complexity that requires a well-planned and defined management strategy. The role
      of the surgeon in caring for these patients should be as the leader of a
      multidisciplinary team, directing the care of the other specialists, all while
      determining if, and when, the patient requires operative intervention. Although
      medical management has come a long way in these and similar patients, surgery is
      still needed in a vast majority of patients. Therefore, understanding the
      evaluation, initial management, and important technical considerations for care
      of IBD and other complex patients with ECFs is a difficult, yet much needed, task
      for which the surgeon should be prepared.

PMID- 21886467
TI  - Enterocutaneous fistula associated with malignancy and prior radiation therapy.
AB  - Enterocutaneous fistula (ECF) associated with cancer or radiation injury
      increases the complexity of normal management. Factors such as timing of
      additional adjuvant therapy or palliative care, technical considerations for
      operating on irradiated bowel, poor wound healing, increased risk of additional
      ECF, and decreased likelihood of spontaneous ECF closure all need to be
      considered in this scenario. Here the authors focus specifically on the
      management of ECF associated with cancer and/or radiation-induced injury to the
      bowel.

PMID- 21886469
TI  - Operative surgery for enterocutaneous fistula.
AB  - The management of the patient with an enterocutaneous fistula is complex and
      requires coordinated care on many fronts for successful elimination. With optimal
      nonoperative management a fistula may heal spontaneously, the majority within the
      first 4 weeks after development. Definitive surgical treatment is best achieved
      with resection of the bowel containing the fistula and anastomosis of healthy
      normal bowel. The timing of definitive surgery appears to be optimal months after
      development, if tolerated. Death rates are low after surgery and patients who
      experience the recurrence of a fistula after initial attempt at closure can
      ultimately still be cured.

PMID- 21886468
TI  - Enterocutaneous fistulas in the setting of trauma and critical illness.
AB  - One of the most devastating complications to develop in the general surgical
      patient is an enterocutaneous fistula (ECF). Critically ill patients suffering
      trauma, thermal injury, infected necrotizing pancreatitis, and other acute
      intraabdominal pathology are at unique risk for this complication as well. By
      using decompressive laparotomy for abdominal compartment syndrome and leaving the
      abdomen open temporarily for other acute processes, survival in some instances
      may be improved. However, the exposed viscera are at risk for fistulization in
      the presence of an open abdomen, a newly defined entity termed the
      enteroatmospheric fistula (EAF). The purpose of this article is to describe the
      epidemiology of ECF in the setting of trauma and critical illness, nutrition in
      injured/critically ill patients with ECF, pharmacologic adjuncts to decrease
      fistula effluent, wound care, surgical management of the EAF/ECF, and techniques
      for prevention of these dreaded complications in patients with an open abdomen.

PMID- 21886470
TI  - Abdominal wall reconstruction in patients with digestive tract fistulas.
AB  - Abdominal wall reconstruction in the digestive tract fistula patient is a complex
      issue. The authors review the available data and present information regarding
      the timing of surgery, techniques of abdominal wall reconstruction, hernia
      repair, and discuss pitfalls associated with the various options. A simple and
      basic approach to this problem is described.

PMID- 21886472
TI  - Urinary tract injuries: recognition and management.

PMID- 21886471
TI  - Complications of enterocutaneous fistulas and their management.
AB  - Complications related to enterocutaneous fistulas are common and include sepsis,
      malnutrition, and fluid or electrolyte abnormalities. Intestinal failure is one
      of the most feared complications of enterocutaneous fistula management and
      results in significant patient morbidity and mortality. The authors review
      emerging trends in the medical and surgical management of patients with
      intestinal failure.

PMID- 21886473
TI  - Letter to the editor.

PMID- 21886474
TI  - Clinical practice guidelines-how do they apply to cardiovascular and pulmonary
      physical therapy?

PMID- 21886475
TI  - Extrinsic Threshold PEEP Reduces Post-exercise Dyspnea in COPD Patients: A
      Placebo-controlled, Double-blind Cross-over Study.
AB  - PURPOSE: Most patients with chronic obstructive pulmonary disease (COPD) complain
      of dyspnea during and following exercise, and the development of intrinsic
      positive end-expiratory pressure (PEEP) is thought to contribute to lung
      hyperinflation and dyspnea. Many people with COPD use pursed lip breathing (PLB)
      in an attempt to produce extrinsic PEEP to reduce lung hyperinflation and dyspnea
      during and following exertion. We hypothesized that the use of a threshold,
      extrinsic PEEP device would reduce post-exercise dyspnea in people with COPD.
      METHODS: A double blind, crossover study was conducted on post-exercise dyspnea
      in 8 patients with COPD whose exercise tolerance was limited by dyspnea. Subjects
      performed two identical 6-minute treadmill bouts that led to a Borg dyspnea
      rating of at least 5/10. Dyspnea, heart rate, and oxygen-hemoglobin saturation
      (SpO(2)) were recorded at rest, every 2 minutes during exercise and at 2, 5, and
      10 minutes post-exercise. Immediately following the exercise bouts, the subjects
      used either a threshold PEEP device for 6 breaths at 10 cm H(2)O or a Sham
      device. RESULTS: Heart rate and SpO(2) were not different between treatments any
      time point before, during, or after exercise. Dyspnea ratings were not different
      between devices at rest or during exercise, but were lower in the post-exercise
      period following use of PEEP (p < 0.05). When asked which device, if any, the
      subjects would prefer to use to relieve post-exercise dyspnea, 7 of 8 chose the
      PEEP device and one had no preference. CONCLUSIONS: We found that the use of a
      PEEP device can help reduce postexercise dyspnea in patients with COPD.

PMID- 21886476
TI  - The Influence of Body Mass Index on Self-report and Performance-based Measures of
      Physical Function in Adult Women.
AB  - PURPOSE: Little is known about limitations in physical function across BMI
      categories in middle aged women using both self-report and performance-based
      measures. Furthermore, the impact of BMI on the measurement of function has not
      been explored. The purpose of this study was to assess physical function in adult
      women across BMI categories using self-report and performance-based measures and
      determine the influence of BMI on the relationship between the measures. METHODS:
      Fifty sedentary females (10 in each BMI category: normal weight, overweight,
      obese class I, II, and III) aged 51.2 +/- 5.4 years participated. Assessments
      included demographics, past medical history, physical activity level, BMI, and
      self-report (Late Life Function and Disability Instrument) and performance-based
      measures of physical function (6-Minute Walk Test, timed chair rise, gait speed).
      Physical function was compared between BMI categories using analysis of variance.
      The influence of BMI on the relationship of self-report and performance-based
      measures was analyzed using linear regression. RESULTS: Compared to those that
      were normal weight or overweight, individuals with obesity scored lower on the
      self-report measure of physical function (LLFDI) for capability in participating
      in life tasks and ability to perform discrete functional activities. On the
      performance-based measures, the individuals with obesity had slower gait speed
      compared to the normal and overweight weight groups. For the 6-Minute Walk Test
      and timed chair stands, individuals with obesity had poorer performance compared
      to those who were normal weight. Linear regression analyses revealed that BMI
      attenuated the relationship between the self-report and performance-based
      measures by approximately 50%. CONCLUSIONS: While those with severe obesity were
      most impaired, adult women with less severe obesity also demonstrated significant
      decrements in physical function.

PMID- 21886477
TI  - A Cardiopulmonary Instructor's Perspective on a Standardized Patient Experience:
      Implications for Cardiopulmonary Physical Therapy Education.
AB  - PURPOSE: Standardized patients (SP) in Doctor of Physical Therapy (DPT) curricula
      are increasingly used for students to practice developing clinical reasoning,
      communication, and professional skills in an authentic learning environment. The
      purposes of this article are to: (1) describe an instructional model that
      synthesized SPs, Internet-based communities of practice, and reflection to teach
      clinical reasoning in DPT students; and (2) a cardiovascular and pulmonary
      physical therapy (CPPT) instructor's perspective on the educational process and
      student clinical skill development. SUMMARY OF KEY POINTS: The model, employed in
      a course: "Integrative Physical Therapy Practice," enabled the instructor to
      document student clinical performance and reasoning during an SP interaction. For
      students, clinical reasoning was illuminated through the model's assessment
      process. Data collected through the assessment process provided important
      feedback to the instructor on classroom instructional effectiveness. CONCLUSIONS:
      Examination of student learning experiences enabled the instructor to consider:
      (1) key aspects of examination and management for persons with cardiovascular or
      pulmonary disorders, (2) methods for visualizing clinical reasoning, (3) the
      impact of teaching on student learning, and (4) strategies for teaching CPPT.
      More research is indicated to investigate pedagogy for the development of
      clinical reasoning in DPT students.

PMID- 21886478
TI  - Physical therapy in the intensive care unit in a patient with biventricular
      assist device.
AB  - PURPOSE: To determine the safety and feasibility of early physical therapy in the
      intensive care unit in a patient with biventricular assist device. METHODS:
      Physical therapy started on the first postoperative day and continued till
      discharge including airway clearance, lower/upper extremity exercises, and
      mobilization. Heart rate (HR), respiratory rate (RR), systolic/diastolic/mean
      arterial pressures, peripheral oxygen saturation, and double product were
      recorded before treatment, after treatment, and 5 minutes after treatment.
      RESULTS: In total, 15 sessions of physical therapy were implemented for a 41-year
      old male patient during 21 days following implantation of a biventricular assist
      device. Normal physiological responses were seen in response to treatment. Heart
      rate increased significantly after treatment in comparison to pretreatment values
      (p = 0.02) and decreased significantly after 5 minutes (p = 0.03) and approached
      pretreatment values. Respiratory rate increased nonsignificantly after treatment
      and decreased significantly after 5 minutes (p = 0.001) and approached
      pretreatment values. CONCLUSION: Physical therapy in the intensive care unit in a
      patient with biventricular assist device resulted in significant increases within
      HR and RR in physiological limits. Ongoing monitoring of vital signs is
      recommended in order to observe physiological responses to early physical
      therapeutic interventions in the intensive care unit.

PMID- 21886479
TI  - How many species are there on Earth and in the ocean?
AB  - The diversity of life is one of the most striking aspects of our planet; hence
      knowing how many species inhabit Earth is among the most fundamental questions in
      science. Yet the answer to this question remains enigmatic, as efforts to sample
      the world's biodiversity to date have been limited and thus have precluded direct
      quantification of global species richness, and because indirect estimates rely on
      assumptions that have proven highly controversial. Here we show that the higher
      taxonomic classification of species (i.e., the assignment of species to phylum,
      class, order, family, and genus) follows a consistent and predictable pattern
      from which the total number of species in a taxonomic group can be estimated.
      This approach was validated against well-known taxa, and when applied to all
      domains of life, it predicts ~8.7 million (+/- 1.3 million SE) eukaryotic species
      globally, of which ~2.2 million (+/- 0.18 million SE) are marine. In spite of 250
      years of taxonomic classification and over 1.2 million species already catalogued
      in a central database, our results suggest that some 86% of existing species on
      Earth and 91% of species in the ocean still await description. Renewed interest
      in further exploration and taxonomy is required if this significant gap in our
      knowledge of life on Earth is to be closed.

PMID- 21886480
TI  - Functional dissection of the proton pumping modules of mitochondrial complex I.
AB  - Mitochondrial complex I, the largest and most complicated proton pump of the
      respiratory chain, links the electron transfer from NADH to ubiquinone to the
      pumping of four protons from the matrix into the intermembrane space. In humans,
      defects in complex I are involved in a wide range of degenerative disorders.
      Recent progress in the X-ray structural analysis of prokaryotic and eukaryotic
      complex I confirmed that the redox reactions are confined entirely to the
      hydrophilic peripheral arm of the L-shaped molecule and take place at a
      remarkable distance from the membrane domain. While this clearly implies that the
      proton pumping within the membrane arm of complex I is driven indirectly via long
      range conformational coupling, the molecular mechanism and the number, identity,
      and localization of the pump-sites remains unclear. Here, we report that upon
      deletion of the gene for a small accessory subunit of the Yarrowia complex I, a
      stable subcomplex (nb8mDelta) is formed that lacks the distal part of the
      membrane domain as revealed by single particle analysis. The analysis of the
      subunit composition of holo and subcomplex by three complementary proteomic
      approaches revealed that two (ND4 and ND5) of the three subunits with homology to
      bacterial Mrp-type Na(+)/H(+) antiporters that have been discussed as prime
      candidates for harbouring the proton pumps were missing in nb8mDelta.
      Nevertheless, nb8mDelta still pumps protons at half the stoichiometry of the
      complete enzyme. Our results provide evidence that the membrane arm of complex I
      harbours two functionally distinct pump modules that are connected in series by
      the long helical transmission element recently identified by X-ray structural
      analysis.

PMID- 21886481
TI  - Tracing the trail of protons through complex I of the mitochondrial respiratory
      chain.
AB  - Mitochondria are the structures that produce the bulk part of the cellular energy
      currency ATP, which drives numerous energy requiring processes in the cell. This
      process involves a series of large enzyme complexes--the respiratory chain--that
      couples the transfer of electrons to the creation of a concentration gradient of
      protons across the inner mitochondrial membrane, which drives ATP synthesis.
      Complex I (or NADH-quinone oxidoreductase) is the largest and by far the most
      complicated of the respiratory chain enzyme complexes. The molecular mechanism
      whereby it couples electron transfer to proton extrusion has remained mysterious
      until very recently. Low-resolution X-ray structures of complex I have,
      surprisingly, suggested that electron transfer in the hydrophilic arm, protruding
      into the mitochondrial matrix, causes movement of a coupling rod that influences
      three putative proton pumps within the hydrophobic arm embedded in the inner
      mitochondrial membrane. In this Primer, we will briefly introduce the recent
      progress made in this area and highlight the road ahead that likely will unravel
      the detailed molecular mechanisms of complex I function.

PMID- 21886482
TI  - Why worry about how many species and their loss?
AB  - We are astonishingly ignorant about how many species are alive on earth today,
      and even more ignorant about how many we can lose yet still maintain ecosystem
      services that humanity ultimately depends upon. Mora et al.'s paper is important
      in offering an imaginative new approach to assessing total species numbers, both
      on land and in the sea.

PMID- 21886483
TI  - Evolution of sex-specific traits through changes in HOX-dependent doublesex
      expression.
AB  - Almost every animal lineage is characterized by unique sex-specific traits,
      implying that such traits are gained and lost frequently in evolution. However,
      the genetic mechanisms responsible for these changes are not understood. In
      Drosophila, the activity of the sex determination pathway is restricted to
      sexually dimorphic tissues, suggesting that spatial regulation of this pathway
      may contribute to the evolution of sex-specific traits. We examine the regulation
      and function of doublesex (dsx), the main transcriptional effector of the sex
      determination pathway, in the development and evolution of Drosophila sex combs.
      Sex combs are a recent evolutionary innovation and show dramatic diversity in the
      relatively few Drosophila species that have them. We show that dsx expression in
      the presumptive sex comb region is activated by the HOX gene Sex combs reduced
      (Scr), and that the male isoform of dsx up-regulates Scr so that both genes
      become expressed at high levels in this region in males but not in females.
      Precise spatial regulation of dsx is essential for defining sex comb position and
      morphology. Comparative analysis of Scr and dsx expression reveals a tight
      correlation between sex comb morphology and the expression patterns of both
      genes. In species that primitively lack sex combs, no dsx expression is observed
      in the homologous region, suggesting that the origin and diversification of this
      structure were linked to the gain of a new dsx expression domain. Two other,
      distantly related fly lineages that independently evolved novel male-specific
      structures show evolutionary gains of dsx expression in the corresponding
      tissues, where dsx may also be controlled by Scr. These findings suggest that
      changes in the spatial regulation of sex-determining genes are a key mechanism
      that enables the evolution of new sex-specific traits, contributing to some of
      the most dramatic examples of phenotypic diversification in nature.

PMID- 21886484
TI  - Three distinct roles for notch in Drosophila R7 photoreceptor specification.
AB  - Receptor tyrosine kinases (RTKs) and Notch (N) proteins are different types of
      transmembrane receptors that transduce extracellular signals and control cell
      fate. Here we examine cell fate specification in the Drosophila retina and ask
      how N acts together with the RTKs Sevenless (Sev) and the EGF receptor (DER) to
      specify the R7 photoreceptor. The retina is composed of many hundred ommatidia,
      each of which grows by recruiting surrounding, undifferentiated cells and
      directing them to particular fates. The R7 photoreceptor derives from a cohort of
      three cells that are incorporated together following specification of the R2-R5
      and R8 photoreceptors. Two cells of the cohort are specified as the R1/6
      photoreceptor type by DER activation. These cells then activate N in the third
      cell (the R7 precursor). By manipulation of N and RTK signaling in diverse
      combinations we establish three roles for N in specifying the R7 fate. The first
      role is to impose a block to photoreceptor differentiation; a block that DER
      activation cannot overcome. The second role, paradoxically, is to negate the
      first; Notch activation up-regulates Sev expression, enabling the presumptive R7
      cell to receive an RTK signal from R8 that can override the block. The third role
      is to specify the cell as an R7 rather than an R1/6 once RTK signaling has
      specified the cells as a photoreceptor. We speculate why N acts both to block and
      to facilitate photoreceptor differentiation, and provide a model for how N and
      RTK signaling act combinatorially to specify the R1/6 and R7 photoreceptors as
      well as the surrounding non-neuronal cone cells.

PMID- 21886485
TI  - Corporate social responsibility and access to policy elites: an analysis of
      tobacco industry documents.
AB  - BACKGROUND: Recent attempts by large tobacco companies to represent themselves as
      socially responsible have been widely dismissed as image management. Existing
      research supports such claims by pointing to the failings and misleading nature
      of corporate social responsibility (CSR) initiatives. However, few studies have
      focused in depth on what tobacco companies hoped to achieve through CSR or
      reflected on the extent to which these ambitions have been realised. METHODS AND
      FINDINGS: Iterative searching relating to CSR strategies was undertaken of
      internal British American Tobacco (BAT) documents, released through litigation in
      the US. Relevant documents (764) were indexed and qualitatively analysed. In the
      past decade, BAT has actively developed a wide-ranging CSR programme. Company
      documents indicate that one of the key aims of this programme was to help the
      company secure access to policymakers and, thereby, increase the company's
      chances of influencing policy decisions. Taking the UK as a case study, this
      paper demonstrates the way in which CSR can be used to renew and maintain
      dialogue with policymakers, even in ostensibly unreceptive political contexts. In
      practice, the impact of this political use of CSR is likely to be context
      specific; depending on factors such as policy elites' understanding of the
      credibility of companies as a reliable source of information. CONCLUSIONS: The
      findings suggest that tobacco company CSR strategies can enable access to and
      dialogue with policymakers and provide opportunities for issue definition. CSR
      should therefore be seen as a form of corporate political activity. This
      underlines the need for broad implementation of Article 5.3 of the Framework
      Convention on Tobacco Control. Measures are needed to ensure transparency of
      interactions between all parts of government and the tobacco industry and for
      policy makers to be made more aware of what companies hope to achieve through
      CSR.

PMID- 21886486
TI  - Government inaction on ratings and government subsidies to the US film industry
      help promote youth smoking.

PMID- 21886487
TI  - Four arguments against the adult-rating of movies with smoking scenes.

PMID- 21886488
TI  - Building the field of health policy and systems research: social science matters.

PMID- 21886490
TI  - Revolutions.

PMID- 21886491
TI  - Report on the ASCO 2010 Provider-Payer Initiative Meeting.
AB  - The ASCO Provider-Payer Initiative meeting was convened to explore ways in which
      providers and payers could work together to improve patient care.

PMID- 21886492
TI  - Current hepatitis B screening practices and clinical experience of reactivation
      in patients undergoing chemotherapy for solid tumors: a nationwide survey of
      medical oncologists.
AB  - PURPOSE: Universal screening for chronic hepatitis B virus (HBV) before
      chemotherapy has been recommended by the Centers for Disease Control. We sought
      to determine the practice of Australian oncologists with regard to HBV screening
      in patients with solid tumors (STs) and their clinical experience of HBV
      reactivation (HBVR). METHODS: A survey was sent to all consultant members of the
      Medical Oncology Group of Australia. One hundred eighty-eight responses (63%
      response rate) were received. We also reviewed the incidence of HBV in patients
      with STs screened at the Peter MacCallum Cancer Centre (Melbourne, Australia).
      RESULTS: Fifty-three percent of medical oncologists screen for HBV, but only 19%
      screen all patients. The most common reasons given for performing screening were
      anecdotal experience of HBVR (46%) and perceived sufficient evidence for
      screening of some patient subgroups (42%). Sixty-five percent of those who
      screened did so only in subgroups, usually selecting patients on the basis of
      ethnicity (82%). Oncologists who did not screen most commonly cited inadequate
      evidence for a benefit of screening (72%). Twenty-two percent of oncologists had
      witnessed one or more HBVR events, representing one event per 45 years of
      respondents' practice. HBVR events reported (n = 54) consisted of asymptomatic
      liver test abnormalities only (44%), symptomatic hepatitis (28%), decompensated
      liver failure (19%), and death (7%). In 206 patients with STs screened for HBV,
      1.0% (n = 2) were HBV surface antigen positive, and 14.9% hepatitis B core
      antibody positive. CONCLUSION: The majority of Australian medical oncologists
      have not adopted universal HBV screening before chemotherapy. Further evidence of
      the benefit and cost effectiveness of universal screening in patients with STs
      will be required to alter practice.

PMID- 21886493
TI  - Characteristics and outcomes of patients with advanced gastric cancer who
      declined to participate in a randomized clinical chemotherapy trial.
AB  - PURPOSE: There is insufficient data to verify whether participation in clinical
      trials in itself can lead to better clinical outcomes. We have analyzed the
      characteristics and outcomes of patients who declined to participate in a
      randomized trial in comparison with those who participated in the trial. PATIENTS
      AND METHODS: A randomized trial for naive advanced gastric cancer was offered to
      286 patients. The trial investigated the superiority of irinotecan plus cisplatin
      and the noninferiority of S-1 compared with continuous fluorouracil infusion. We
      retrospectively reviewed the characteristics and outcomes for both participants
      and nonparticipants in this trial. RESULTS: Of the 286 patients, 98 (34%)
      declined to participate in the trial. The rate of declining was significantly
      higher among younger patients (P = .003), and it varied significantly between
      attending physicians (range, 23% to 58%; P = .004). There were no other
      significant correlations between rate of declining and patient characteristics.
      No significant differences were observed in the clinical outcomes between the
      participants and nonparticipants, for whom the median survival times were 367
      versus 347 days, respectively. The hazard ratio for overall survival, adjusted
      for other confounding variables, was 1.21 (95% CI, 0.91 to 1.60). No interaction
      was observed between participation and the various regimens. CONCLUSION: There
      was no difference in clinical outcomes between participants and nonparticipants.
      However, the patient's age and the doctor-patient relationship may have an effect
      on patient accrual to randomized trials.

PMID- 21886494
TI  - Commentary: clinical trials represent the best cancer care. Or do they?

PMID- 21886495
TI  - Diagnostic imaging and biopsy use among elderly medicare beneficiaries with
      hepatocellular carcinoma.
AB  - PURPOSE: Diagnostic imaging is effective for evaluating patients suspected of
      having hepatocellular carcinoma (HCC). Although the diagnosis can be established
      with imaging alone, diagnostic biopsy may be useful for patients with tumors
      measuring 1 to 2 cm. To date, biopsy and imaging use among patients with HCC has
      not been evaluated in the general community. PATIENTS AND METHODS: This cohort
      study used Surveillance, Epidemiology, and End Results (SEER) -Medicare data
      (2002-2005) evaluating biopsy, imaging modalities (ultrasound, computed
      tomography [CT] scan, and/or magnetic resonance imaging [MRI]), and HCC risk
      factors. RESULTS: Of 3,696 patients, 1,197 (32.4%) underwent one or more
      biopsies, with no change in yearly biopsy rate (trend test, P = .64). Patients
      with tumors > 5 cm were most likely to receive biopsies (35.3%), with increasing
      rates of biopsy for larger tumors (P = .001). Patients who received biopsies
      underwent more imaging than those who did not (P < .001) and were more likely to
      have an HCC risk factor. Tumor size > 5 cm in the setting of a concurrent HCC
      risk factor increased the odds of biopsy. In 47.8% of patients, the diagnostic
      sequence was not consistent with contemporary evidence-based guidelines.
      CONCLUSIONS: Despite widespread availability and use of CT scan and MRI, one
      third of HCC patients undergo biopsy, suggesting a problem with the performance
      and/or quality of diagnostic imaging or that providers do not believe imaging
      alone is sufficient to establish the diagnosis. Understanding factors that drive
      biopsy use may help improve the care of patients with HCC.

PMID- 21886497
TI  - Spanish as a primary language and its effect on breast cancer presentation.
AB  - PURPOSE: It is well documented that patients without health insurance tend to
      present at more advanced cancer stages than those with insurance. What has not
      been well documented is the effect that primary language has on cancer stage
      presentation. Given the significant number uninsured patients and patients not
      fluent in English who are treated at our institution, we sought to identify how
      these parameters affect cancer staging at presentation using breast cancer as a
      model. METHODS: We conducted a retrospective chart review over a 36-month period
      at an urban community hospital. Patients who received their initial surgical
      treatment at this facility were included. One hundred seventy patients were
      identified. Definitive breast cancer surgery, breast cancer stage, and type were
      recorded for all subjects. We analyzed patient demographics including ethnicity,
      primary language spoken, and insurance status. RESULTS: All patients were female.
      Patient populations were evenly distributed among three major ethnicities: 39%
      were African American, 36% were white, 23% were Hispanic, and 2% were listed as
      "other." Seventy percent of Hispanic patients noted that English was not their
      primary language. Ten percent of the white population presented at stage III or
      greater compared with 16% of African Americans and 22% of Hispanics. Twenty-seven
      percent of non-English-speaking Hispanics presented with advanced-stage disease.
      CONCLUSION: Non-English-speaking Hispanic patients presented at more advanced
      stages than their English-speaking counterparts. Health care reform must address
      the non-English-speaking Hispanic to effectively improve the health of all groups
      in the United States.

PMID- 21886496
TI  - A screening tool to enhance clinical trial participation at a community center
      involved in a radiation oncology disparities program.
AB  - PURPOSE: To investigate the effectiveness of a screening tool to enhance clinical
      trial participation at a community radiation oncology center involved in a
      National Cancer Institute-funded disparities program but lacking on-site clinical
      trials personnel. PATIENTS AND METHODS: The screening form was pasted to the
      front of the charts and filled out for all new patients over the 9-month period
      of the study, during which time five external beam radiation therapy (EBRT)
      trials and a patient perception study were open for accrual. Patient consent was
      obtained by assorted personnel at several different sites. Patients potentially
      eligible for a trial were identified and approached by one of the clinic staff.
      Patients who were under- or uninsured, age > 80 years, members of an
      racial/ethnic minority, or recipients of medical assistance were identified as at
      risk for health care disparities and were offered patient navigator services.
      RESULTS: Of 196 patients consulted during the study, 144 were treated with EBRT.
      Of the 24 patients eligible for EBRT trials, 23 were approached (one had an
      incomplete screening form), and 15 accepted. Of 77 patients eligible for a
      patient perception trial, 72 were approached (five had incomplete forms), and 45
      accepted. The eligibility and acceptance rates for EBRT trials were similar for
      disparities and nondisparities patients. Screening was completed for 96 patients
      (67%). CONCLUSION: When completed, the screening tool ensured clinical trial
      accrual. The major factor limiting overall accrual was a shortage of available
      trials.

PMID- 21886498
TI  - A model for rural oncology.
AB  - Small rural hospitals in the United States have had challenging issues developing
      sustainable oncology programs. This is a report on the development of a
      successful rural oncology program. In 2006, the Tahoe Forest Health System in
      Truckee, CA, a remote mountain resort town, started a cancer program that was
      focused on addressing patient and family fears that are common to all cancer
      patients but more frightening in the rural setting. Four years later, it is a
      thriving program with significant community support, a creative academic
      affiliation, and a central focus of the future of the hospital. The Tahoe Forest
      Cancer Center developed a sustainable model for high quality cancer care that
      overcomes geographic, cultural and financial barriers. This structure may serve
      as a model for national rural health care.

PMID- 21886499
TI  - Barriers to recruitment of rural patients in cancer clinical trials.
AB  - PURPOSE: The National Cancer Institute estimates that less than 5% of adult
      patients with cancer participate in clinical trials. This statistic has to
      improve in order for clinical trials to be more accurate and generalizable.
      Several studies have looked into the barriers to accrual among various patient
      subgroups. However, there are scant data regarding factors that act as barriers
      to accrual of rural patients. Our study aims to identify these barriers. PATIENTS
      AND METHODS: Among patients seen at the Mary Babb Randolph Cancer Center at West
      Virginia University, 1,000 were randomly selected to receive a questionnaire by
      mail. Data obtained consisted of demographic and clinical information, as well as
      awareness about clinical trials, willingness to participate, and factors
      influencing participation. Patients had 6 weeks to respond. RESULTS: Two hundred
      forty-one (24.1%) patients responded to the survey. Of these, 66.9% had heard
      about clinical trials, 19.6% reported that their health care team had discussed
      clinical trials, and 9.1% had participated in clinical trials. Respondents were
      more likely to be willing to participate in cancer prevention/screening trials
      than therapeutic trials. Regarding the decision not to participate in a clinical
      trial, patients cited discouragement from their oncologist, monetary burden,
      discouragement from family physician, commute, and lack of information as
      strongly or extremely influential factors. CONCLUSION: Our findings specify the
      need for patient and physician education through community outreach programs.
      Oncologists should be trained to discuss clinical trials and to address concerns
      regarding their availability, utility, and accessibility. Financial counseling
      may play an important role in improving accrual rates as well.

PMID- 21886500
TI  - National cancer institute conference on treating tobacco dependence at cancer
      centers.
AB  - The National Cancer Institute cancer centers possess the credibility to help
      smokers quit. With the greater life expectancies forecast for patients with
      cancer, addressing smoking at cancer centers has taken on greater importance.

PMID- 21886501
TI  - Physicians' current practices and opportunities for DNA banking of dying patients
      with cancer.
AB  - PURPOSE: The availability of genetic tests for cancer susceptibility is
      increasing. Current tests, however, have limited clinical sensitivity. Even when
      clinically valid tests are available, the genetic counseling and informed consent
      process might not be feasible for dying patients with cancer. DNA banking
      preserves the opportunity for future research or clinical testing and may provide
      critical opportunities for surviving relatives. This study explored the current
      practices and potential for DNA banking for cancer susceptibility among
      oncologists specializing in palliative care. METHODS: Palliative care oncologists
      actively providing clinical care for dying patients with cancer were recruited
      for an online survey. Descriptive statistics for DNA banking practices, perceived
      qualification to recommend banking, and potential predictors were assessed.
      RESULTS: Data were collected from 49 physicians (37% recruitment rate). Eighty
      percent reported assessing at least some patients for genetic cancer
      susceptibility in the past 12 months. No participants reported banking DNA for
      patients in the past 12 months. Only 5% reported feeling at least somewhat
      qualified to order DNA banking. A Web-based risk assessment tool and genetic
      counselor on staff were perceived as the most helpful potential resources.
      CONCLUSION: Despite its potential, DNA banking is not being used by palliative
      care oncologists.

PMID- 21886502
TI  - The clinical research team.
AB  - Developing and maintaining an exemplary research team is essential to the success
      of a quality clinical research program.

PMID- 21886503
TI  - Partners and partnerships: trends in private oncology practice.
AB  - There are approximately 6,500 medical oncologists in private practice in the
      United States. Regional vacancy rates can range from 30% to 50%, putting enormous
      stress on existing providers. Regulatory, financial and emotional burdens
      continue to restructure the medical marketplace.

PMID- 21886504
TI  - Subspecialization in community oncology: option or necessity?
AB  - Specializing in a particular type of cancer is one way to manage the explosion of
      knowledge in oncology. What would subspecializing mean for practitioners,
      patients, and the community?

PMID- 21886505
TI  - ASCO Provisional Clinical Opinion: Epidermal Growth Factor Receptor Mutation
      Testing in Practice.
AB  - ASCO has recently provided guidance on emerging data on EGFR testing for the
      purpose of selecting first-line therapy for persons with advanced NSCLC through
      its Provisional Clinical Opinion.

PMID- 21886506
TI  - Racial variation in the cost-effectiveness of chemotherapy for prostate cancer.
AB  - PURPOSE: Heterogeneity of treatment effects and expenditures impacts the cost
      effectiveness of health interventions. This study investigates the variation in
      costs, effects, and incremental cost-effectiveness ratios (ICERs) associated with
      chemotherapy in elderly patients with metastatic (M1) prostate cancer (PC) across
      race/ethnicity subgroups (non-Hispanic whites, non-Hispanic blacks, and others).
      STUDY DESIGN: Retrospective observational analysis. METHODS: We examined patients
      age 66 years or older, identified by using the linked Surveillance, Epidemiology,
      and End Results-Medicare data set, who were diagnosed with M1 PC between 2000 and
      2005. Cost data on the basis of Medicare reimbursements were available for 36
      months after diagnosis. Mean costs and effects (life-years gained [LYG]) were
      adjusted for censoring. The baseline scenario examined PC-specific medical costs
      at 24 months and required survival of at least three months. Sensitivity analysis
      considered sampling uncertainty, selection into treatment, and adjustments to
      initial model assumptions. RESULTS: We identified 3,888 patients with M1 PC, of
      whom 24% (n = 930) received chemotherapy (primarily docetaxel and mitoxantrone).
      Twenty percent of observations were censored. The full sample ICER was $99,146
      per LYG (95% CI, $75,042 to $130,195). Estimates for whites (ICER, $107,095; 95%
      CI, $78,391 to $148,272), blacks (ICER, $59,887; 95% CI, $22,860 to $121,509),
      and others (ICER, $123,909; 95% CI, $37,782 to $366,376) suggest considerable
      variation in the likelihood of chemotherapy being cost-effective. Results were
      similar in sensitivity analysis. CONCLUSION: Chemotherapy use in elderly patients
      with M1 PC is associated with an ICER of $99,146 per LYG. Subgroup analysis
      revealed heterogeneity in point estimates and considerable statistical
      uncertainty. To generate a reliable evidence base, efforts to increase the
      representation of minorities in health care data sets need to continue.

PMID- 21886507
TI  - Genomic testing and therapies for breast cancer in clinical practice.
AB  - PURPOSE: Given the likely proliferation of targeted testing and treatment
      strategies for cancer, a better understanding of the utilization patterns of
      human epidermal growth factor receptor 2 (HER2) testing and trastuzumab and newer
      gene expression profiling (GEP) for risk stratification and chemotherapy decision
      making are important. STUDY DESIGN: Cross-sectional. METHODS: We performed a
      medical record review of women age 35 to 65 years diagnosed between 2006 and 2007
      with invasive localized breast cancer, identified using claims from a large
      national health plan (N = 775). RESULTS: Almost all women received HER2 testing
      (96.9%), and 24.9% of women with an accepted indication received GEP. Unexplained
      socioeconomic differences in GEP use were apparent after adjusting for age and
      clinical characteristics; specifically, GEP use increased with income. For
      example, those in the lowest income category (< $40,000) were less likely than
      those with an income of $125,000 or more to receive GEP (odds ratio, 0.34; 95%
      CI, 0.16 to 0.73). A majority of women (57.7%) with HER2-positive disease
      received trastuzumab; among these women, differences in age and clinical
      characteristics were not apparent, although surprisingly, those in the lowest
      income category were more likely than those in the high-income category to
      receive trastuzumab (P = .02). Among women who did not have a positive HER2 test,
      3.9% still received trastuzumab. Receipt of adjuvant chemotherapy increased as
      GEP score indicated greater risk of recurrence. CONCLUSION: Identifying and
      eliminating unnecessary variation in the use of these expensive tests and
      treatments should be part of quality improvement and efficiency programs.

PMID- 21886508
TI  - Impact of clinical oral chemotherapy program on wastage and hospitalizations.
AB  - PURPOSE: The oral chemotherapy cycle management program (CMP) provides clinical
      management support to patients receiving certain oral chemotherapies. The CMP
      includes a dose-monitoring (ie, split-fill) plan for early identification and
      management of adverse effects. If serious adverse effects are identified mid
      cycle, the remainder of the monthly supply is withheld, thus avoiding potential
      waste associated with early therapy discontinuation. This study investigated
      medication wastage and estimated potential cost savings for patients who were
      enrolled in the CMP, as compared with those who were not enrolled in the program.
      STUDY DESIGN: Retrospective test-control study. PATIENTS AND METHODS: Patients
      whose oral chemotherapy was initiated between June 2008 and February 2010 and who
      were enrolled in the CMP were included as the test group. Patient whose oral
      chemotherapy was initiated between June 2007 and May 2008 and who were not part
      of the CMP were included as the control group. RESULTS: Medication wastage
      associated with early therapy discontinuation was found to be lower in the CMP
      group. Approximately 34% of patients in the CMP group could have avoided
      medication wastage if split-fill plans had been available, potentially realizing
      savings of approximately $934.20 per patient. Linear probability regression
      models showed that the CMP group had a 2.9% probability for reduction in hospital
      admissions (P < .05), resulting in additional savings of approximately $440.0 per
      patient. Combined savings resulting from reduced wastage and hospital admissions
      was approximately $1,374 per patient. CONCLUSION: Dose-monitoring programs such
      as the CMP effectively reduce wastage and serious adverse effects associated with
      oral chemotherapeutic agents, realizing potential cost savings for both payers
      and patients.

PMID- 21886509
TI  - Impact of new drugs and biologics on colorectal cancer treatment and costs.
AB  - PURPOSE: To compare medical expenditures of patients receiving old and new
      colorectal cancer (CRC) regimens. STUDY DESIGN: USING CLAIMS DATA, WE IDENTIFIED
      TWO COHORTS OF PRIVATELY INSURED PATIENTS DIAGNOSED WITH CRC: first, those
      diagnosed before new treatment introduction (January 1, 2002, to December 31,
      2002), and second, those diagnosed after new treatment introduction (June 1,
      2004, to May 31, 2005). CRC diagnosis was identified using International
      Classification of Diseases-9 codes 153.xx, 154.xx, and 159.0. First- and second
      line chemotherapy regimens were identified. Treatments and expenditures were then
      observed for up to 2 years after initial diagnosis. METHODS: We estimated
      multivariate models to measure changes in cost with changes in treatment regimen.
      Approval dates of new regimens were used as natural experiments. RESULTS: New
      regimens, such as fluorouracil, leucovorin, and oxaliplatin (FOLFOX), have
      rapidly replaced the most prevalent preperiod product (ie,
      fluorouracil/leucovorin). Changes in treatment have caused large increases in
      total expenditure, primarily through increases in chemotherapy prices. FOLFOX
      alone has increased total average cost by 14%. New treatments have not
      substituted other medical services; rather, they have indirectly raised costs
      through nonstandard regimen use and increases in second-line treatment use. We
      found no evidence that expenditure effects were driven by changes in follow-up
      duration. CONCLUSION: New CRC treatments have increased both regimen choice and
      expenditures. New regimens have primarily increased expenditures through direct
      treatment costs; we observed no offsetting expenditure reductions.

PMID- 21886510
TI  - US Insurance Program's Experience With a Multigene Assay for Early-Stage Breast
      Cancer.
AB  - PURPOSE: National guidelines recommend a 21-gene recurrence score (RS) to aid in
      adjuvant treatment decision in patients with estrogen receptor (ER) -positive,
      lymph node (LN) -negative early-stage breast cancer (ESBC). This study was
      performed to assess the economic implication of the assay in community practices
      from the perspective of a US payer. METHODS: The study analyzed 952 women with
      ESBC enrolled with Humana (Louisville, KY) who were tested with the 21-gene RS
      between June 2006 and June 2010. The proportion of women classified by the assay
      according to RS risk category, use, and costs of chemotherapy regimens and
      supportive care, and costs of adverse events were obtained from Humana. We
      adopted a validated Markov model to compute the cost implications of RS for a
      representative patient. The probability of risk of recurrence, the chemotherapy
      benefit, and the decision impact of RS were derived from published studies.
      RESULTS: Two hundred fifty-five patients within the tested population received
      adjuvant chemotherapy. Adjuvant chemotherapy was administered to 10% of women at
      low risk, 36% of women at intermediate risk, and 72% of women at high risk of
      recurrence. On the basis of a meta-analysis in the reduction of chemotherapy
      after RS, the model estimated an average test saving of $1,160 per patient. The
      immediate direct savings for chemotherapy drugs, supportive care, and management
      of adverse events were $1,885, $2,578, and $472, respectively. Prevention of
      recurrence through appropriate treatment of patients at high risk resulted in
      additional savings of $199. CONCLUSION: The adoption of the 21-gene RS led to
      targeted management of women with ER-positive, LN-negative ESBC and consequently
      directed savings to the payer.

PMID- 21886511
TI  - Oncology management programs for payers and physicians: evaluating current models
      and diagnosing successful strategies for payers and physicians.

PMID- 21886512
TI  - Journey forward: the new face of cancer survivorship care.

PMID- 21886514
TI  - Developing dialogue in health care.

PMID- 21886513
TI  - Effect of the Pay-for-Performance Program for Breast Cancer Care in Taiwan.
AB  - PURPOSE: To evaluate the impact of the nationwide pay-for-performance (P4P)
      program for breast cancer care (BC-P4P) in Taiwan on care quality, patient
      survival, and recurrence. STUDY DESIGN: A population-based observational study
      with cross-sectional design. METHODS: Retrospective analysis of population-based
      cancer registration and claims data was used in this study. A total of 4,528
      patients with stage I or II breast cancer diagnosed in 2002 or 2003 who received
      curative surgery were observed until the end of 2008. This study applied
      multivariate linear regression to explore the association between BC-P4P
      enrollment and quality of care. Cox regression was applied to examine the effect
      of BC-P4P enrollment on 5-year recurrence and overall survival among patients
      with breast cancer. RESULTS: After controlling for age, stage, type of surgery,
      and other factors, BC-P4P enrollees were found to have received better quality
      care than nonenrollees (P = .001). Cox regression models also indicated that
      after controlling for patient characteristics, quality of care was related to
      better 5-year overall survival (odds ratio [OR], 0.212; P = .001) and recurrence
      (OR, 0.289; P < .001). Even when controlled by quality of care provided to
      patients and its interaction with status of BC-P4P enrollment, BC-P4P enrollment
      remained statistically significant regarding 5-year overall survival (OR, 0.167;
      P < .001) and recurrence (OR, 0.370; P = .002). CONCLUSION: Patients with breast
      cancer enrolled in the BC-P4P program received better quality care and had better
      outcome than nonenrolled patients. Evidence from this study indicates that
      financial incentives in the payment design had a positive impact on outcome of
      breast cancer care.

PMID- 21886515
TI  - Health technology assessment and private payers' coverage of personalized
      medicine.
AB  - PURPOSE: Health technology assessment (HTA) plays an increasing role in
      translating emerging technologies into clinical practice and policy. Private
      payers are important users of HTA whose decisions impact adoption and use of new
      technologies. We examine the current use of HTA by private payers in coverage
      decisions for personalized medicine, a field that is increasingly impacting
      oncology practice. STUDY DESIGN: Literature review and semistructured interviews.
      METHODS: We reviewed seven HTA organizations used by private payers in decision
      making and explored how HTA is used by major US private payers (n = 11) for
      coverage of personalized medicine. RESULTS: All payers used HTA in coverage
      decisions, but the number of HTA organizations used by an individual payer ranged
      from one (n = 1) to all seven (n = 1), with the majority of payers (n = 8) using
      three or more. Payers relied more extensively on HTAs for reviews of personalized
      medicine (64%) than for other technologies. Most payers (82%) equally valued
      expertise of reviewers and rigor of evaluation as HTA strengths, whereas genomic
      specific methodology was less important. Key reported shortcomings were limited
      availability of reviews (73%) and limited inclusion of nonclinical factors (91%),
      such as cost-effectiveness or adoption of technology in clinical practice.
      CONCLUSION: Payers use a range of HTAs in their coverage decisions related to
      personalized medicine, but the current state of HTA to comprehensively guide
      those decisions is limited. HTA organizations should address current gaps to
      improve their relevance to payers and clinicians. Current HTA shortcomings may
      also inform the national HTA agenda.

PMID- 21886516
TI  - Characterizing medical care by disease phase in metastatic colorectal cancer.
AB  - PURPOSE: To characterize patterns of medical care by disease phase in patients
      with newly diagnosed metastatic colorectal cancer (mCRC). METHODS: Patients with
      mCRC newly diagnosed between 2004 and 2008 were selected from a large US national
      commercially insured claims database and were observed from initial mCRC
      diagnosis to death, disenrollment, or end of study period (July 31, 2009),
      whichever occurred first. The observation period was divided into three distinct
      phases of disease: diagnostic, treatment, and death. Within each phase, patterns
      of medical care were examined by the mutually exclusive service categories of
      inpatient, emergency room (ER), outpatient office and facility, outpatient
      pharmacy, chemotherapy, and biologic therapy, as measured by estimation of
      aggregate and category costs per patient per month. RESULTS: A total of 6,675
      patients with newly diagnosed mCRC were analyzed. Mean age was 64.1 years; 55.5%
      were males. Mean costs per patient per month for diagnostic, treatment, and death
      phases were $16,895, $8,891, and $27,554, respectively. Inpatient care was the
      primary driver of medical care for both the diagnostic (41.7% of costs) and death
      (71.4% of costs) phases. The largest category of medical care for the treatment
      phase was outpatient care (45.0% of costs). Chemotherapy and biologic therapy
      accounted for 15.6% and 17.6% of costs in the treatment phase, respectively.
      CONCLUSION: Substantial differences in patterns of medical care were found
      between mCRC disease phases. Inpatient care was the key driver of medical care in
      the diagnostic and death phases compared with outpatient care in the treatment
      phase.

PMID- 21886517
TI  - Advancing performance measurement in oncology: quality oncology practice
      initiative participation and quality outcomes.
AB  - The American health care system, including the cancer care system, is under
      pressure to improve patient outcomes and lower the cost of care. Government
      payers have articulated an interest in partnering with the private sector to
      create learning communities to measure quality and improve the value of health
      care. In 2006, the American Society for Clinical Oncology (ASCO) unveiled the
      Quality Oncology Practice Initiative (QOPI), which has become a key component of
      the measurement system to promote quality cancer care. QOPI is a physician-led,
      voluntary, practice-based, quality-improvement program, using performance
      measurement and benchmarking among oncology practices across the United States.
      Since its inception, ASCO's QOPI has grown steadily to include 973 practices as
      of November 2010. One key area that QOPI has addressed is end-of-life care.
      During the most recent data collection cycle in the Fall of 2010, those practices
      completing multiple data collection cycles had better performance on care of pain
      compared with sites participating for the first time (62.61% v 46.89%).
      Similarly, repeat QOPI participants demonstrated meaningfully better performance
      than their peers in the rate of documenting discussions of hospice and palliative
      care (62.42% v 54.65%) and higher rates of hospice enrollment. QOPI demonstrates
      how a strong performance measurement program can lead to improved quality and
      value of care for patients.

PMID- 21886519
TI  - Patient and plan characteristics affecting abandonment of oral oncolytic
      prescriptions.
AB  - PURPOSE: To calculate the abandonment rate of oral oncolytic medications and
      identify factors that may affect likelihood of abandonment. STUDY DESIGN: Cross
      sectional cohort study using administrative claims data. METHODS: We analyzed a
      nationally representative pharmacy claims database and identified 10,508 patients
      with Medicare and commercial insurance for whom oral oncolytic therapy was
      initiated between 2007 and 2009. We calculated the abandonment rate for the
      initial claim, in which abandonment was defined as reversal of an adjudicated
      pharmacy claim without a subsequent paid claim for any oncolytic (oral or
      intravenous) within the ensuing 90 days. We assessed likelihood of abandonment
      using bivariate and multivariate logistic regression analyses including patient
      demographics, plan type, drug type, cost sharing, and concurrent prescription
      activity. RESULTS: The abandonment rate of newly initiated oral oncolytics was
      10.0%. Unadjusted bivariate analyses found that high cost sharing, increased
      prescription activity, lower income, and Medicare coverage were associated with a
      higher abandonment rate (P < .05). In the logistic regression model, claims with
      cost sharing greater than $500 were four times more likely to be abandoned than
      claims with cost sharing of $100 or less (odds ratio [OR], 4.46; P < .001).
      Patients with five or more prescription claims processed within in the previous
      month had 50% higher likelihood of abandonment than patients with no other
      prescription activity (OR, 1.50; P < .001). CONCLUSION: Abandonment of newly
      prescribed oral oncolytic therapy is not uncommon, and the likelihood increases
      for patients enrolled in plans with pharmacy benefit designs that require high
      cost sharing. Increased concurrent prescription activity was also associated with
      a higher abandonment rate. These factors should be taken into account when
      considering likely adherence to cancer therapy.

PMID- 21886518
TI  - Do economic evaluations of targeted therapy provide support for decision makers?
AB  - PURPOSE: Decision makers must make decisions without complete information. That
      uncertainty can be decreased when economic evaluations use local data and can be
      quantified by considering the variability of all model inputs concurrently per
      international evaluation guidelines. It is unclear how these recommendations have
      been implemented in evaluations of targeted cancer therapy. By using economic
      evaluations of adjuvant trastuzumab, we have assessed the extent to which
      decision support recommendations were adopted. STUDY DESIGN: Systematic review.
      METHODS: Published economic evaluations of adjuvant trastuzumab treatment in
      early-stage breast cancer were examined as an established example of targeted
      therapy. Canadian, United Kingdom, and US economic evaluation guidelines were
      reviewed to establish extraction criteria. Extraction characterized the use of
      effectiveness evidence and local data sources for model parameters, sensitivity
      analysis methods (scenario, univariate, multivariate, and probabilistic) and
      uncertainty representation (ie, cost-effectiveness plane, scatterplot, confidence
      ellipses, tornado diagrams, cost-effectiveness acceptability curve). RESULTS:
      Fifteen economic evaluations of adjuvant trastuzumab were identified in the
      literature. Local data were used to estimate costs (15 of 15) and utilities
      rarely (two of 15) but not trastuzumab efficacy. Univariate sensitivity analysis
      was most common (12 of 15), whereas probabilistic analysis was less frequent (10
      of 15). Two thirds of all studies provided visual representation of results and
      decision uncertainty. CONCLUSION: Authors of adjuvant trastuzumab economic
      evaluations rarely use local data beyond costs. Quantification of uncertainty and
      its representation also fell short of guideline recommendations. This review
      demonstrates that economic evaluations of adjuvant trastuzumab, as an example of
      targeted cancer therapy, can be improved for decision-making support.

PMID- 21886521
TI  - Trying something new: episode payments for cancer therapy.

PMID- 21886520
TI  - Pathways, outcomes, and costs in colon cancer: retrospective evaluations in two
      distinct databases.
AB  - PURPOSE: The goal of this study was to use two separate databases to evaluate the
      clinical outcomes and the economic impact of adherence to Level I Pathways, an
      evidence-based oncology treatment program in the treatment of colon cancer.
      PATIENTS AND METHODS: The first study used clinical records from an electronic
      health record (EHR) database to evaluate survival according to pathway status in
      patients with colon cancer. Disease-free survival in patients receiving adjuvant
      treatment and overall survival in patients receiving first-line therapy for
      metastatic disease was calculated. The second study used claims data from a
      national administrative claims database to examine direct medical costs and use,
      including the cost of chemotherapy and of chemotherapy-related hospitalizations
      according to pathway status. RESULTS: Overall costs from the national claims
      database-including total cost per case and chemotherapy costs-were lower for
      patients treated according to Level I Pathways (on-Pathway) compared with
      patients not treated according to Level I Pathways. Use of pathways was also
      associated with a shorter duration of therapy and lower rate of chemotherapy
      related hospital admissions. Survival for patients on-Pathway in the EHR database
      was comparable with those in the published literature. CONCLUSION: Results from
      two distinct databases suggest that treatment of patients with colon cancer on
      Pathway costs less; use of these pathways demonstrates clinical outcomes
      consistent with published evidence.

PMID- 21886522
TI  - Are we winning the war on cancer?

PMID- 21886523
TI  - Giving back to your country, the people, and your family.

PMID- 21886524
TI  - The Hospital for Special Surgery 1972-1989; Philip D. Wilson, Jr., Eighth Surgeon
      in-Chief.
AB  - After nearly a decade as the seventh Surgeon-in-Chief (1963-1972) of The Hospital
      for Special Surgery (HSS), Robert Lee Patterson, Jr., MD (1907-1994) retired,
      having repaired adverse relations between HSS and the New York Hospital-Cornell
      Medical Center. Patterson, who had first joined the staff of The Hospital for the
      Ruptured and Crippled in 1936 as a Visiting Surgeon, was able to accomplish this
      very challenging task mainly through his close relationship with Preston Wade, MD
      (1901-1982), a general surgeon who had served with Patterson as Co-Chief of the
      combined New York Hospital-HSS Fracture service. The Board of Trustees of the New
      York Society for the Relief of the Ruptured and Crippled appointed Philip D.
      Wilson, Jr. MD, as the eighth Surgeon-in-Chief of The Hospital for Special
      Surgery. He assumed that office on July 1, 1972. Wilson, who had joined the staff
      as an Orthopaedic Surgeon to the Out-Patient Department in 1951, had trained as
      an orthopaedic resident at HSS from 1948 to 1950 and in 1951, finished his
      residency at the University of California Hospital Medical Center, San Francisco.
      During his 17 years as Surgeon-in-Chief, he led the hospital into the advanced
      field of implant research and development and building a world-class center for
      patient care. Additionally, many other orthopaedic services such as Sports
      Medicine, Scoliosis and Metabolic Bone Diseases became the leaders in their
      fields. Supporting Departments of Rheumatology, Anesthesia and others were
      likewise recognized foremost in the country.

PMID- 21886525
TI  - Failure of the Patellar Tendon with the Patella Everted versus Noneverted in a
      Matched-Pair Cadaver Model.
AB  - Avoidance of patellar eversion during total knee arthroplasty may help to prevent
      injury to the patellar tendon. The purpose of this study was to compare the load
      to-failure of the everted versus the noneverted patella in a cadaveric model.
      Fourteen cadaver knees (seven pairs) were loaded to failure with the patella
      everted in one knee and not everted in the other. Mean load-at-ultimate failure
      in the patella-everted group was 1,111 +/- 572 N, and in the patella-noneverted
      group was 1,621 +/- 683 N (p = 0.01). Additionally, loads-at-initial-partial
      failure were lower (p = 0.04) in the patella-everted compared to the patella
      noneverted group, 573 +/- 302 N versus 1,115 +/- 358 N, respectively. A partial
      failure of the patellar tendon occurred in 100% of the everted specimens, whereas
      only 57% of the noneverted specimens had partial failure. These findings suggest
      patella eversion may lead to failure of the patellar insertion at lower loads
      than when the patella is not everted.

PMID- 21886527
TI  - Arthroscopic capsular plication in the treatment of shoulder pain in competitive
      swimmers.
AB  - Shoulder pain is a common and difficult problem in competitive swimmers due to
      cumulative loads from repetitive overhead motion. Capsular laxity has been
      implicated as a potential etiology for shoulder pain in competitive swimmers. No
      study has examined the role of capsular plication in addressing recurrent
      shoulder pain in competitive swimmers. The purpose of this study is to
      retrospectively describe our series of competitive swimmers treated with
      arthroscopic capsular plication with a primary outcome of return to competitive
      swimming. Eighteen shoulders in 15 patients underwent arthroscopic capsular
      plication from 2003 to 2007. Patients were contacted at an average follow-up of
      29 months (range, 8-42) and a swimming history, American Shoulder and Elbow
      (ASES) scores, and L'Insalata scores were obtained. At time of surgery, all
      patients demonstrated laxity under examination under anesthesia. All patients had
      a positive drive-through sign. Eighty percent (12/15) of patients returned to
      competitive swimming although only 20% (3/15) were able to return to their pre
      injury training regimen volume. All patients subjectively reported improved pain
      after surgery. The average ASES score was 78 +/- 16 (average, standard
      deviation). The average L'Insalata score was 82 +/- 11. Although our results
      demonstrate that arthroscopic capsular plication has utility in the treatment of
      shoulder pain in swimmers who have failed non-operative treatment, the inability
      of some athletes to return to pre-injury training volume illustrates the
      difficult nature of shoulder pain in swimmers. LEVEL OF EVIDENCE: Retrospective
      case series, Level IV.

PMID- 21886526
TI  - High-flexion total knee replacement: functional outcome at one year.
AB  - Implants designed for enhanced flexion offer the prospect of improved function
      after total knee replacement (TKR). Whereas most studies evaluating these
      implants have focused on the range of knee flexion achieved, this study
      investigated the quality of function in deep knee flexion. The influences of
      residual pain and maximum flexion angle on function in deep knee flexion were
      also examined. Eighty-three patients (100 knees) were prospectively followed for
      1 year after TKR with a rotating-platform posterior-stabilized high-flexion
      prosthesis. Range of motion was measured and Knee Society scores were calculated.
      A questionnaire evaluated residual knee pain and function in high-flexion
      activities. Mean Knee Society score was 95, and mean knee flexion was 125 degrees
      , yet 20% of patients could neither kneel, nor squat, nor sit on their heels.
      Fifty-seven percent were able to kneel without significant difficulty; 69% were
      able to squat without significant difficulty; and 46% were able to sit on their
      heels without significant difficulty. Function in deep flexion correlated with
      pain scores but did not correlate with knee flexion angles or Knee Society
      scores. Results 1 year after TKR with a rotating-platform posterior-stabilized
      high-flexion prosthesis are encouraging, but one in five patients remain
      significantly limited in high-flexion activities.

PMID- 21886528
TI  - Early Post-operative Periprosthetic Femur Fracture in the Presence of a Non
      cemented Tapered Wedge Femoral Stem.
AB  - Non-cemented femoral fixation in hip arthroplasty has become the standard of
      practice in the USA. However, recent literature has brought attention to an
      increasing incidence of periprosthetic femur fractures with certain stem designs.
      This study examines reasons for early periprosthetic femur fractures in patients
      with a hip arthroplasty performed using a non-cemented tapered wedge stem design.
      A multivariate analysis using a matched-cohort design was performed to assess any
      potential risk factors that may predispose to such fractures. Six of 2,220 hips
      (0.3%) suffered a periprosthetic femur fracture within the first year after
      surgery; five of six were Vancouver Type B2. The average time to fracture was 9
      weeks. This group of patients had a significantly higher canal-flare index and
      lower canal-calcar ratio. This complication may be preventable by having a better
      appreciation of the fit between the implant and the bone during pre-operative
      planning, with the goal of avoiding a proximal-distal mismatch.

PMID- 21886529
TI  - A randomized controlled trial of intraarticular ropivacaine for pain management
      immediately following total knee arthroplasty.
AB  - Total knee arthroplasty (TKA) is a commonly performed procedure for the treatment
      of end-stage arthritis of the knee. Pain control following TKA is difficult to
      manage in some patients. We examined the use of a postoperative intraarticular
      injection of 100 mL of 0.2% (200 mg) ropivacaine in a double-blind, prospective,
      placebo-controlled pilot study to evaluate its use as a pain control modality.
      All patients received general anesthesia. Postoperatively, patients were placed
      on intravenous patient-controlled analgesia with morphine. The ropivacaine group
      showed an early trend in lower visual analog scale (VAS) scores when compared
      with the placebo group. Patients receiving ropivacaine used a similar amount of
      narcotics compared with the placebo group. Intraarticular ropivacaine used for
      pain control after TKA demonstrated no statistically significant difference in
      lowering VAS scores or narcotic usage; therefore, intraarticular ropivacaine as a
      single modality is not recommended for effective pain management.

PMID- 21886530
TI  - The utility of urine desmosine as a marker of lung injury in spine surgery.
AB  - The objective of this prospective observational study was to determine if urine
      desmosine levels, a marker of lung injury, increase in response to the
      periopreative insults of anterior and posterior spine surgery. Desmosine, a
      stable breakdown product of elastin, has been proposed as a surrogate marker of
      lung injury in patients with COPD, tobacco use, and ARDS. We recently evaluated
      this marker in patients undergoing knee surgery, but the utility of desmosine as
      a marker of lung injury in patients undergoing spine surgery remains unstudied.
      In this study, we enrolled ten consecutive patients, who underwent
      anterior/posterior spine surgery. Patient demographics and perioperative data
      were recorded. Urine samples were collected at baseline, 1 day, and 3 days
      postoperatively and analyzed for levels of desmosine using a previously validated
      radioimmunoassay. Desmosine levels were 35.9 +/- 18.2 pmol/mg creatinine at
      baseline, 38.7 +/- 11 pmol/mg creatinine on postoperative day 1, and 70.5 +/-
      49.1 pmol/mg creatinine on postoperative day 3, respectively.
      Desmosine/creatinine ratios measured on day 3 postoperatively were significantly
      elevated compared to levels at baseline, and represented a 96.3% increase. No
      difference was seen between levels at baseline and day 1 postoperatively. In
      conclusion, we were able to show a significant increase in urine desmosine levels
      associated with anterior/posterior spine surgery. In the context of previous
      studies, our findings suggest that desmosine may be a marker of lung injury in
      this setting. However, further research is warranted for validation and
      correlation of desmosine levels to clinical markers and various degrees of lung
      injury.

PMID- 21886531
TI  - Histologic stages of healing correlate with restoration of tensile strength in a
      model of experimental tendon repair.
AB  - Much current research is focused on biologic enhancement of the tendon repair
      process. To evaluate the different methods, which include a variety of gene
      therapy and tissue engineering techniques, histological and biomechanical testing
      is often employed. Both modalities offer information on the progress and quality
      of repair; however, they have been historically considered as two separate
      entities. Histological evaluation is a less costly undertaking; however, there is
      no validated scoring scale to compare the results of different studies or even
      the results within a given study. Biomechanical testing can provide validated
      outcome measures; however, it is associated with increased cost and is more labor
      intensive. We hypothesized that a properly developed, objective histological
      scoring system would provide a validated outcome measure to compare histological
      results and correlate with biomechanics. In an Achilles tendon model, we have
      developed a histological scoring scale to assess tendon repair. The system grades
      collagen orientation, angiogenesis, and cartilage induction. In this study,
      histology scores were plotted against biomechanical testing results of healing
      tendons which indicated that a strong linear correlation exists between the
      histological properties of repaired tendons and their biomechanical
      characteristics. Concordantly, this study provides a pragmatic and financially
      feasible means of evaluating repair while accounting for both the histology and
      biomechanical properties observed in surgically repaired, healing tendon.

PMID- 21886533
TI  - Sonographic evaluation and sonographic-guided therapeutic options of lateral
      ankle pain: peroneal tendon pathology associated with the presence of an os
      peroneum.
AB  - Clinical implications of acute injuries of the os peroneum have been described,
      with the recommendation in some cases being the excision of the bone fragments.
      We describe the spectrum of sonographic appearances associated with pain in the
      region of the os peroneum, document associated peroneal tendon pathology, and
      describe the use of sonography to direct and guide therapeutic and/or diagnostic
      injections. All sonographic examinations in our ultrasound database from Jan 1,
      2001-Jan 30, 2007 with the words "os peroneum" were reviewed. Patients were cross
      referenced in our radiology database to find relevant foot or ankle radiographs
      for correlation. There were 47 patients (18 men and 29 women, age range 16 to 83)
      referred for sonographic evaluation of lateral foot and/or ankle pain who had an
      os peroneum identified during the sonographic evaluation. Eighteen patients were
      referred specifically for targeted injection of the lateral ankle, including
      peroneal tendon sheath injections (N = 10), calcaneocuboid joint injections (N =
      1), and injections around symptomatic os peroneum (N = 7). All 47 patients had
      tendinosis of the peroneus longus, in varying degrees of severity. Radiographs
      were available for correlation in 28 patients. The causes of lateral ankle pain
      with a co-existent os peroneum are multifactorial and may not directly relate to
      the presence of an os peroneum. Ultrasound can be of value in separating out the
      specific etiology for pain, as well as provide a method for problem solving by
      the performance of targeted diagnostic or therapeutic injections in the lateral
      ankle.

PMID- 21886532
TI  - Aggrecan and cartilage oligomeric matrix protein in serum and synovial fluid of
      patients with knee osteoarthritis.
AB  - Aggrecan and cartilage oligomeric matrix protein (COMP) which are important
      degradation products of articular cartilage may be promising diagnostic markers
      in serum and/or synovial fluid for diagnosis of knee osteoarthritis (OA). Our
      objective was to measure serum and synovial fluid levels of aggrecan and COMP in
      patients with OA of the knee joint to find out if they could be of diagnostic
      value in OA and if their levels correlate with the clinical and radiological
      manifestations of the disease. Sixty-six patients suffering from primary knee OA
      with effusion (26 males and 40 females) were studied. Twenty individuals (six
      males and 14 females) with recent traumatic knee effusion matched for age and sex
      were chosen to serve as a control group. All subjects had thorough clinical and
      radiological (X-ray and MRI) evaluation. Aggrecan and COMP in serum and synovial
      fluid were measured by ELISA. Serum and synovial fluid aggrecan and COMP levels
      were significantly higher than the control. Serum and synovial fluid aggrecan and
      COMP levels were positively correlated with age, body mass index, disease
      duration, plain X-ray and MRI scores. In OA, serum and synovial fluid aggrecan
      and COMP levels are elevated and represent useful markers in the diagnosis.
      Moreover, these elevated levels positively correlated with radiological joint
      damage but not with clinical disease parameters. These markers have the potential
      to be used for monitoring articular cartilage destruction and response to
      different therapeutic modalities.

PMID- 21886534
TI  - The management of patients on dual antiplatelet therapy undergoing orthopedic
      surgery.
AB  - Cardiovascular disease is prevalent in patients undergoing orthopedic surgery.
      Many patients who have undergone previous percutaneous coronary intervention
      (PCI) with stenting are on dual antiplatelet therapy in order to minimize the
      risk of stent thrombosis. The optimal management of these patients in the
      perioperative setting remains unclear. We aim to provide information about the
      management of patients who have undergone a PCI with stents who are subsequently
      indicated for an orthopedic procedure. We will review the concerns from a
      cardiologist's and orthopedic surgeon's perspective in regards to the management
      of these patients in the perioperative setting. In addition, the current American
      Heart Association, American College of Cardiology, Society for Cardiovascular
      Angiography and Interventions, and American College of Surgeons guidelines are
      reviewed. The decision to discontinue dual antiplatelet therapy in a patient who
      has undergone a PCI with stent should be made only after careful review of the
      risks for thrombosis and bleeding. Best practice suggests that these risks should
      be jointly assessed by the orthopedic surgeon and cardiologist. Those patients
      with stents at high risk of thrombosis should have surgery delayed if possible.
      There is little data supporting a significantly increased bleeding risk
      associated with mortality in orthopedic patients when antiplatelet therapy is
      continued perioperatively.

PMID- 21886535
TI  - Alternative procedures for reducing allogeneic blood transfusion in elective
      orthopedic surgery.
AB  - Perioperative blood loss is a major problem in elective orthopedic surgery.
      Allogeneic transfusion is the standard treatment for perioperative blood loss
      resulting in low postoperative hemoglobin, but it has a number of well-recognized
      risks, complications, and costs. Alternatives to allogeneic blood transfusion
      include preoperative autologous donation and intraoperative salvage with
      postoperative autotransfusion. Orthopedic surgeons are often unaware of the
      different pre- and intraoperative possibilities of reducing blood loss and leave
      the management of coagulation and use of blood products completely to the
      anesthesiologists. The goal of this review is to compare alternatives to
      allogeneic blood transfusion from an orthopedic and anesthesia point of view
      focusing on estimated costs and acceptance by both parties.

PMID- 21886537
TI  - Large-vessel granulomatous vasculitis in Crohn's disease: a clinical pathology
      conference held by the division of rheumatology at hospital for special surgery.

PMID- 21886536
TI  - Parsonage-turner syndrome.
AB  - Parsonage-Turner Syndrome (PTS), also referred to as idiopathic brachial
      plexopathy or neuralgic amyotrophy, is a rare disorder consisting of a complex
      constellation of symptoms with abrupt onset of shoulder pain, usually
      unilaterally, followed by progressive neurologic deficits of motor weakness,
      dysesthesias, and numbness. Although the etiology of the syndrome is unclear, it
      is reported in various clinical situations, including postoperatively,
      postinfectious, posttraumatic, and postvaccination. The identification of the
      syndrome in the postoperative patient remains a challenge as symptoms may easily
      be attributed to sequelae of surgical positioning, postoperative recovery, or
      postanesthetic block pain. The purpose of this review is to bring forth salient,
      identifiable factors which may assist the surgical clinician in identifying the
      condition sooner. An early and proper diagnosis affords the opportunity to treat
      the patient accordingly and to the satisfaction of both surgeon and patient.

PMID- 21886538
TI  - Traumatic Lateral Plantar Artery Pseudoaneurysm and the Use of Time-Resolved MR
      Angiography.
AB  - Vascular injury resulting in pseudoaneurysm formation in the plantar aspect of
      the foot is an uncommon injury after trauma. Such injuries are more often
      reported in the lateral plantar artery rather than the medial plantar artery,
      most likely because of its more superficial location. Traditional modalities in
      diagnosis have included ultrasound and digital subtraction angiography. We
      present a case of traumatic pseudoaneurysm of the lateral plantar artery
      following a foot laceration. Diagnosis was made by the use of high-resolution,
      time-resolved contrast-enhanced 3D magnetic resonance angiography, also referred
      to as "TRICKS" (time-resolved imaging of contrast kinetics). This technique
      provided high spatial resolution for the arterial anatomy as well as temporal
      resolution which allowed better delineation of the hemodynamic characteristics of
      the pseudoaneurysm. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this
      article (doi:10.1007/s11420-010-9170-3) contains supplementary material, which is
      available to authorized users.

PMID- 21886539
TI  - Revision knee arthroplasty including reconstruction of the lateral collateral
      ligament by allograft: a case report.
AB  - A 53-year-old woman presented with an unstable and painful total knee
      arthroplasty 6 months after the index procedure. Disruption of both collateral
      ligaments as a young adult and the subsequent development of traumatic arthritis
      required repeated surgical and extensive conservative treatment before a
      prosthesis was implanted. Examination disclosed marked instability of the lateral
      collateral ligament (LCL) and loosening of the tibial and the femoral components.
      Review of the MRI obtained prior to the total knee replacement revealed
      discontinuity of the LCL with intense scarring of the posterolateral ligament
      complex. Definitive management of this twofold problem was not helped by
      literature review, which failed to reveal a gold standard or a broad consensus as
      a rationale for treatment. Consequently, an individual approach to the problem
      was defined: A one-stage revision arthroplasty was performed using a modular non
      articulated constrained prosthesis and a bone-tendon-bone allograft to
      reconstruct the LCL in a one-stage operation. Postoperative rehabilitation
      included continuous passive motion, which was begun immediately after surgery and
      was gradually increased to 90 degrees  of flexion. The LCL reconstruction was
      initially protected in a hinged knee brace and weight-bearing was initially
      limited to toe-touch and gradually increased over 6 weeks. Pain-free motion to 0
      115 degrees  flexion was achieved at 3 months after surgery and the patient had
      returned to her normal activities. The 4-year-follow-up displayed a stable and
      functional knee with no evidence of loosening or wear.

PMID- 21886540
TI  - Arthroscopic anterior and posterior labral repair after traumatic hip
      dislocation: case report and review of the literature.
AB  - With the improvements in flexible instrumentation, hip arthroscopy is being
      increasingly used to treat a variety of hip pathology, including labral tears.
      However, up to this point, there has not been a case report of an anterior and a
      posterior labral tear successfully repaired arthroscopically. We present a case
      report of a 27-year-old male firefighter who presented to our institution with an
      anterior and posterior labral tear, as well as a cam lesion and loose body,
      following a traumatic hip dislocation. The purpose of this case report is to
      illustrate that both anterior and posterior labral tears can be repaired using
      hip arthroscopy. Anterior and posterior labral tears can be caused by a traumatic
      hip dislocation, and both can be successfully repaired using arthroscopic
      techniques.

PMID- 21886541
TI  - Traumatic osteochondral injury of the femoral head treated by mosaicplasty: a
      report of two cases.
AB  - The increased risk of symptomatic progression towards osteoarthritis after
      chondral damage has led to the development of multiple treatment options for
      cartilage repair. These procedures have evolved from arthroscopic lavage and
      debridement, to marrow stimulation techniques, and more recently, to
      osteochondral autograft and allograft transplants, and autogenous chondrocyte
      implantation. The success of mosaicplasty procedures in the knee has led to its
      application to other surfaces, including the talus, tibial plateau, patella, and
      humeral capitellum. In this report, we present two cases of a chondral defect to
      the femoral head after a traumatic hip dislocation, treated with an osteochondral
      autograft (OATS) from the ipsilateral knee, and the inferior femoral head,
      respectively, combined with a surgical dislocation of the hip. At greater than 1
      year and greater than 5 years of follow-up, MRI studies have demonstrated good
      autograft incorporation with maintenance of articular surface conformity, and
      both patients clinically continue to have no pain and full active range of motion
      of their respective hips. In our opinion, treatment of osteochondral defects in
      the femoral head surface using a surgical dislocation combined with an OATS
      procedure is a promising approach, as full exposure of the femoral head can be
      obtained while preserving its vasculature, thus enabling adequate restoration of
      the articular cartilage surface.

PMID- 21886542
TI  - A modified surgical technique for lengthening of a metatarsal using an external
      fixator.
AB  - Brachymetatarsia is a congenital or developmental condition that results in a
      short metatarsal. Problems that arise from this condition can include pain,
      difficulty with shoe wear, and cosmetic concerns. Multiple techniques have been
      described that successfully correct the deformity, including both acute and
      gradual distraction. We describe a modification of the technique of gradual
      lengthening by way of distraction osteogenesis in which an axial transarticular K
      wire is incorporated into a monolateral frame, thereby increasing the stability
      of the construct and potentially minimizing complications.

PMID- 21886543
TI  - Estimators of The Magnitude-Squared Spectrum and Methods for Incorporating SNR
      Uncertainty.
AB  - Statistical estimators of the magnitude-squared spectrum are derived based on the
      assumption that the magnitude-squared spectrum of the noisy speech signal can be
      computed as the sum of the (clean) signal and noise magnitude-squared spectra.
      Maximum a posterior (MAP) and minimum mean square error (MMSE) estimators are
      derived based on a Gaussian statistical model. The gain function of the MAP
      estimator was found to be identical to the gain function used in the ideal binary
      mask (IdBM) that is widely used in computational auditory scene analysis (CASA).
      As such, it was binary and assumed the value of 1 if the local SNR exceeded 0 dB,
      and assumed the value of 0 otherwise. By modeling the local instantaneous SNR as
      an F-distributed random variable, soft masking methods were derived incorporating
      SNR uncertainty. The soft masking method, in particular, which weighted the noisy
      magnitude-squared spectrum by the a priori probability that the local SNR exceeds
      0 dB was shown to be identical to the Wiener gain function. Results indicated
      that the proposed estimators yielded significantly better speech quality than the
      conventional MMSE spectral power estimators, in terms of yielding lower residual
      noise and lower speech distortion.

PMID- 21886544
TI  - Role of the HLA System in the Pathogenesis of Dupuytren's Disease.
AB  - Dupuytren's disease (DD) is a familial, fibroproliferative, irreversible, and
      progressive disease of the palmar fascia, yet with unknown etiology. However,
      there is compelling evidence which has consistently suggested a genetic
      ethiopathogenesis given the high occurrence among the Northern European
      extraction, familial nature, and demonstration of concordance in twins. DD is an
      incurable, recurrent, and potentially debilitating disease with limited and
      ineffective treatments. Although a number of possible candidate genes have been
      investigated including matrix metalloproteinases (MMPs) and transforming growth
      factor-beta (TGF-beta) genes, as yet, no consistent genetic biomarker has been
      identified for DD. The highly polymorphic human leukocyte antigen (HLA) region is
      an ideal biomarker target. There have been some coherent data within the
      literature to suggest a genotype to phenotype association between certain HLA
      loci and a number of fibrotic disorders such as keloid and scleroderma, markedly
      with class II molecules and disease pervasiveness and clinical progression. The
      aim of this review, therefore, was to investigate the evidence indicative of both
      positive and negative associations between particular HLA alleles and DD. There
      is a clear association with specific HLA alleles and predilection or protection
      to DD, though there is a pressing need for further supportive data. The most
      promising of links to the HLA region in terms of a definitive genetic biomarker
      is with the class II HLA-DR loci. This paper presents a detailed account of the
      immunogenetic component of DD and explores the possible mechanisms of association
      between specific HLA molecules and susceptibility to DD.

PMID- 21886545
TI  - Kinematic Analysis of Six Different Insertion Sites for FDS Opponensplasty.
AB  - Six variations of opponensplasty were biomechanically studied to determine if
      there is a significant difference in the amount of opposition produced by
      altering the insertion site of the tendon transfer while keeping the tendon
      source and pulley location constant. Five cadaveric arms were used to simulate
      six described insertion sites for opponensplasty tendon transfers. The arms were
      mounted through the ulna onto a specially designed stand. The stand was equipped
      with a calibrated stylus which could be turned 90 degrees  in order to accurately
      measure points in X, Y, and Z planes. Metacarpal-phalangeal flexion and thumb
      abduction were measured before and after application of a 550-g load. Axial
      rotation (pronation) was mathematically calculated using reference points on the
      thumb which were measured with the stylus before and after application of the
      load. The Bunnell transfer insertion site provided the greatest amount of palmar
      abduction, the Brand transfer insertion site the greatest metacarpophalangeal
      flexion, and the Royle transfer insertion site the greatest rotation. Although
      each of these transfers produced the greatest motion in one plane, they performed
      relatively poorly in the other two. The Riordan transfer insertion site into the
      extensor pollicis longus in line with the abductor pollicis brevis was, in our
      study, the overall best transfer, providing the second greatest change in motion
      in each of the three planes measured.

PMID- 21886546
TI  - Measurement of ulnar variance on uncalibrated digital radiographic images.
AB  - Uncalibrated digital radiographs used in multicenter trials hinder quantitative
      measures such as articular step and ulnar variance. This investigation tested the
      reliability of alternative measures of ulnar variance that are scaled to the
      length of the capitate. A sample of 30 sets of radiographs from patients enrolled
      in a prospective study of operative treatment of fractures of the distal radius
      were blinded and randomized. Five observers measured the ulnar variance (UV) and
      longitudinal length of the capitate (CH) on two separate occasions with greater
      than 2 weeks between measurements. During each measurement session, the observers
      made the measurements on both a calibrated and a noncalibrated workstation. The
      ratio of the ulnar variance to the length of capitate was calculated (UV/CH
      ratio). Paired t tests were used to compare two rounds of measurements for both
      methods. Intra- and interobserver reliability was assessed by the Pearson product
      moment correlation coefficients. The ratios were compared using analysis of
      variance with a Bonferroni correction. The intraobserver reliability was
      excellent for each of the three variables (UV, CH, UV/CH ratio) for each
      workstation. The interobserver reliability of the UV/CH ratios obtained for each
      workstation was moderate to excellent as judged by the Pearson correlations
      between observers. The Bland-Altman method indicated a mean difference in UV/CH
      between calibrated and uncalibrated measurement techniques of 0.002 with limits
      of agreement of -0.11 to 0.11. Measurements of ulnar variance that are scaled to
      the length of the capitate may be useful measures of deformity in studies that
      utilize uncalibrated digital radiographs.

PMID- 21886547
TI  - Referring physicians' knowledge of hand surgery.
AB  - Hand surgeons rely on referrals from general providers. Appropriate referral is
      dependent upon referring physicians having an understanding of the problem and
      available treatments. This study evaluates the referring physicians' knowledge
      and perceptions of basic hand problems and their treatment. This study also
      evaluates the impact of a brief lecture on our referring physicians'
      understanding of hand issues. A survey instrument was administered to referring
      physicians. The instrument addressed general hand knowledge and perceptions
      toward hand surgery. The physicians also attended a lecture on general hand
      problems and their treatments. The survey was repeated 2 weeks post-lecture.
      Subjects had a pre-lecture knowledge score of 65% correct and post-lecture a
      score of 85%, p < 0.05. The participants were knowledgeable about common hand
      problems, such as carpal tunnel syndrome. Knowledge gaps did exist, for example,
      only 37% recognized the symptoms of basilar thumb arthritis. Initially, the
      referring physicians had less positive views about surgical interventions, such
      as surgery to help the pain of basilar thumb arthritis. After the lecture, the
      responders had significantly more favorable attitudes toward surgery. This study
      found that referring physicians had variable knowledge about common hand
      problems, and they had doubts relating to the efficacy of some hand surgeries.
      This study also found that a directed lecture improved these providers' knowledge
      and their perceptions of hand surgical interventions. Hand surgeons can improve
      their referring physicians understanding and perceptions of hand surgery through
      a directed grand rounds type lecture.

PMID- 21886548
TI  - Multiple modality treatment regimen in an aggressive resistant fungal hand
      infection: a case report.
AB  - Cutaneous fungal infections are a rare but significant complication associated
      with immunocompromised states. Lesions allowed to progress to disseminated
      fungemia are associated with a near 80% mortality rate. Treatment guidelines
      aimed at local control are vague, centering on wide local excision with systemic
      antifungal medications. We present the case of a 3-year-old female who, while
      receiving induction chemotherapy, developed a progressive Aspergillus flavus
      infection. Involvement included the distal palm and common and proper
      neurovascular bundles to two fingers. Initial treatments with serial debridement
      and topical Dakin's solution were unsuccessful in eliminating this fungal
      infection. A novel treatment using topical voriconazole mixed with Aquaphor(r)
      (Beiersdorf AG; Hamburg, Germany) was compounded in the hospital pharmacy to
      maintain a moist wound healing environment followed by the use of the Vacuum
      Assisted Closure (VAC(r), Kinetic Concepts, San Antonio, TX). Significant
      improvement was noted within 4 days with this new dressing regimen. Topical
      voriconazole therapy followed by VAC allowed progressive healing and eventual
      closure with a split thickness skin graft. The wound was then durably closed,
      allowing critical chemotherapy to resume. No evidence of systemic fungemia
      developed, and her clinical recovery preceded laboratory evidence of immune
      system recovery. Fungal skin infections can be a threat to both life and limb in
      immunocompromised patients. The armamentarium available to combat this rare but
      difficult problem is imperfect. In certain infections not responsive to other
      therapies, the therapeutic regimen described herein should be considered if wide
      local excision carries significant functional morbidity.

PMID- 21886549
TI  - The dorsal metacarpal artery perforator flap: a case report utilizing a quaba
      flap harvested from a previously skin-grafted area for dorsal 5th digit coverage.
AB  - Burns to the hand are common in burn victims. These burns often leave complex
      wounds that require local flaps for coverage. Local flaps are often excluded
      because they lie within the zone of thermal injury. The purpose of this case
      report is to report the successful use of a Quaba flap harvested from a
      previously burned and skin-grafted area. The patient's medical record including
      pre-operative, intra-operative, and post-operative photographs were reviewed and
      utilized as sources of data. The patient tolerated the procedure well and was
      able to return to his previous hand therapy regimen without adverse event and
      with an acceptable cosmetic result. The Quaba flap can be a safe and effective
      option for local hand coverage even in previously burned and skin-grafted areas.

PMID- 21886550
TI  - Supraclavicular approach for thoracic outlet syndrome.
AB  - The authors' experience with the supraclavicular approach for the treatment of
      patients with primary thoracic outlet syndrome (TOS) and for patients with
      recurrent TOS or iatrogenic brachial plexus injury after prior transaxillary
      first rib resection is presented. The records of 33 patients (34 plexuses) with
      TOS who presented for evaluation and treatment were analyzed. Of these, 12 (35%)
      plexuses underwent surgical treatment, and 22 (65%) plexuses were managed non
      operatively. The patients who were treated non-operatively and had an adequate
      follow-up (n = 11) were used as a control group. Of the 12 surgically treated
      patients, five patients underwent primary surgery; four patients had secondary
      surgery for recurrent TOS; and three patients had surgery for iatrogenic brachial
      plexus injury. All patients presented with severe pain, and most of them had
      neurologic symptoms. All nine (100%) patients who underwent primary surgery (n =
      5) and secondary surgery for recurrent TOS (n = 4) demonstrated excellent or good
      results. On the other hand, six (54%) of the 11 patients from the control group
      had some benefit from the non-operative treatment. Reoperation in three patients
      with iatrogenic brachial plexus injury resulted in good result in one case and in
      fair results in two patients; however, all patients were pain-free. No
      complications were encountered. Supraclavicular exploration of the brachial
      plexus enables precise assessment of the contents of the thoracic inlet area. It
      allows for safe identification and release of all abnormal anatomical structures
      and complete first rib resection with minimal risk to neurovascular structures.
      Additionally, this approach allows for the appropriate nerve reconstruction in
      cases of prior transaxillary iatrogenic plexus injury. ELECTRONIC SUPPLEMENTARY
      MATERIAL: The online version of this article (doi:10.1007/s11552-009-9253-0)
      contains supplementary material, which is available to authorized users.

PMID- 21886551
TI  - Understanding the Global Problem of Drug Addiction is a Challenge for IDARS
      Scientists.
AB  - IDARS is an acronym for the International Drug Abuse Research Society. Apart from
      our scientific and educational purposes, we communicate information to the
      general and scientific community about substance abuse and addiction science and
      treatment potential. Members of IDARS are research scientists and clinicians from
      around the world, with scheduled meetings across the globe. IDARS is developing a
      vibrant and exciting international mechanism not only for scientific interactions
      in the domain of addiction between countries but also ultimately as a resource
      for informing public policy across nations. Nonetheless, a lot more research
      needs to be done to better understand the neurobiological basis of drug addiction
      - A challenge for IDARS scientists.

PMID- 21886552
TI  - Exploring mechanisms underlying extinction of cue-elicited cocaine seeking.
AB  - A prominent feature of drug addiction is that drug-associated cues can elicit
      drug-seeking behaviors and contribute significantly to the high propensity to
      relapse. We have been investigating the notion that the dopamine D1 receptor and
      the immediate early gene product c-Fos expressed in D1 receptor-bearing neurons
      mediate the development of persistent neuroadaptation in the brain dopamine
      system by regulating cell signaling and gene expression. We generated and
      analyzed genetically engineered mouse models and found that the D1 receptor and c
      Fos expressed in D1 receptor-bearing neurons mediate the locomotor sensitization
      and reinforcing effects of cocaine. Moreover, these molecules regulate cocaine
      induced dendritic remodeling, electrophysiological responses, and changes in cell
      signaling and gene expression in the brain. Notably, a lack of Fos expression in
      D1 receptor-bearing neurons in mice results in no change in the induction but a
      significantly delayed extinction of cocaine-induced conditioned place preference.
      These findings suggest that D1 receptor-mediated and c-Fos-regulated changes in
      cell signaling and gene expression may play key roles in the extinction process,
      and they provide a foundation for further exploring mechanisms underlying
      extinction of cue-elicited cocaine seeking.

PMID- 21886553
TI  - CART Peptides Regulate Psychostimulants and May be Endogenous Antidepressants.
AB  - CART peptides are endogenous neurotransmitters that are involved in a variety of
      physiologic functions. Injection of CART 55-102 into the nucleus accumbens
      produces no effect, but when co-administered with cocaine, it reduces the
      locomotor and rewarding properties of cocaine. In a human study, subjects
      carrying a missense mutation of the CART gene exhibited increased anxiety and
      depression. Also, several animal studies support the idea that CART is involved
      in anxiety and depression, and they also suggest several possible mechanisms by
      which this may occur. Thus, there is interesting evidence that CART peptides play
      a role in anxiety and depression, and that CART peptides may be endogenous
      antidepressants.

PMID- 21886554
TI  - Parthenolide Blocks Cocaine's Effect on Spontaneous Firing Activity of
      Dopaminergic Neurons in the Ventral Tegmental Area.
AB  - Chronic cocaine administration leads to catecholamine reuptake inhibition which
      enhances reward and motivational behaviors. Ventral Tegmental Area dopaminergic
      (VTA DA) neuronal firing is associated with changes in reward predictive signals.
      Acute cocaine injections inhibit putative VTA DA cell firing in vertebrates.
      Parthenolide, a compound isolated from the feverfew plant (Tanacetum parthenium),
      has been shown to substantially inhibit cocaine's locomotion effects in a
      planarian animal model (Pagan et al., 2008). Here we investigated the effects of
      parthenolide on the spontaneous firing activity of putative VTA DA neurons in
      anesthetized male rats (250-300g). Single-unit recordings were analyzed after
      intravenous (i.v.) parthenolide administration followed by 1mg/kg i.v. cocaine
      injection. Results showed that parthenolide at 0.125 mg/kg and 0.250mg/kg
      significantly blocked cocaine's inhibitory effect on DA neuronal firing rate and
      bursting activity (p< 0.05, two way ANOVA). We propose that parthenolide might
      inhibit cocaine's effects on VTA DA neurons via its interaction with a common
      binding site at monoamine transporters. It is suggested that parthenolide could
      have a potential use as an overdose antidote or therapeutic agent to cocaine
      intoxication.

PMID- 21886555
TI  - The inhibition of histone deacetylases reduces the reinstatement of cocaine
      seeking behavior in rats.
AB  - Drug addiction is a chronic brain disease characterized by a persistent risk of
      relapse, even after a long period of abstinence. A current hypothesis states that
      relapse results from lasting neuroadaptations that are induced in response to
      repeated drug administration. The adaptations require gene expression, some of
      which being under the control of stable epigenetic regulations. We have
      previously demonstrated that pretreatment with histone deacetylase (HDAC)
      inhibitors reduces the cocaine reinforcing properties as well as the motivation
      of rats for cocaine. We show here that the same HDAC inhibitors, trichostatin A
      and phenylbutyrate, significantly reduced the cocaine-seeking behavior induced by
      the combination of a cocaine injection together with the exposure to a light cue
      previously associated with cocaine taking. Reinstatement of drug-seeking behavior
      was carried out after a 3-week withdrawal period, which came after ten daily
      sessions of cocaine intravenous self-administration. Our results suggest that
      pharmacological treatment aimed at modulating epigenetic regulation, and
      particularly treatment that would inhibit HDAC activity, could reduce the risk of
      relapse, a major drawback in the treatment of drug addiction.

PMID- 21886556
TI  - Gastrodia Elata Bl Attenuates Cocaine-Induced Conditioned Place Preference and
      Convulsion, but not Behavioral Sensitization in Mice: Importance of GABA(A)
      Receptors.
AB  - It has been suggested that GABAergic neurotransmission can modulate cocaine
      dependence and seizure activity. Since Gastrodia elata Bl (GE), an oriental herb
      agent, has been shown to enhance GABAergic transmission, we examined whether GE
      affects cocaine-induced seizures, conditioned place preference (CPP), and
      behavioral sensitization in mice. Treatment with GE (500 or 1000 mg/kg, p.o.)
      significantly delayed seizure onset time and significantly shortened seizure
      duration induced by cocaine (90 mg/kg, i.p.). In addition, cocaine (15 mg/kg,
      i.p.)-induced CPP was significantly attenuated by GE in a dose-dependent manner.
      However, GE did not significantly alter behavioral sensitization induced by
      cocaine (15 mg/kg, i.p.). In order to understand whether GABAergic receptors are
      implicated in GE-mediated pharmacological action in response to cocaine, GABA(A)
      receptor antagonist bicuculline and GABA(B) receptor antagonist SCH 50911 were
      employed in the present study. GE-mediated attenuations on the cocaine-induced
      seizures and CPP were significantly reversed by bicuculline (0.25 or 0.5 mg/kg,
      i.p.), but not by SCH 50911 (1.5 or 3.0 mg/kg, i.p.). Therefore, our results
      suggest that GE attenuates cocaine-induced seizures and CPP via, at least in
      part, GABA(A) receptor activation.

PMID- 21886557
TI  - Liquiritigenin decreases selective molecular and behavioral effects of cocaine in
      rodents.
AB  - Cocaine, as an indirect dopamine agonist, induces selective behavioral and
      physiological events such as hyperlocomotion and dopamine release. These changes
      are considered as consequences of cocaine-induced molecular adaptation such as
      CREB and c-Fos. Recently, methanolic extracts from licorice was reported to
      decrease cocaine-induced dopamine release and c-Fos expression in the nucleus
      accumbens. In the present study, we investigated the effects of liquiritigenin
      (LQ), a main compound of licorice, on acute cocaine-induced behavioral and
      molecular changes in rats. LQ attenuated acute cocaine-induced hyperlocomotion in
      dose-dependent manner. In addition, LQ inhibited CREB phosphorylation and c-Fos
      expression in the striatum and the nucleus accumbens induced by acute cocaine.
      Results provide strong evidence that LQ effectively attenuates the acute
      behavioral effects of cocaine exposure and prevents the induction of selective
      neuroadaptive changes in dopaminergic signaling pathways. Further investigation
      of LQ from licorice extract might provide a novel therapeutic strategy for the
      treatment of cocaine addiction.

PMID- 21886558
TI  - Long-term protective effects of methamphetamine preconditioning against single
      day methamphetamine toxic challenges.
AB  - Methamphetamine (METH) use is associated with neurotoxic effects which include
      decreased levels of dopamine (DA), serotonin (5-HT) and their metabolites in the
      brain. We have shown that escalating METH dosing can protect against METH induced
      neurotoxicity in rats sacrificed within 24 hours after a toxic METH challenge.
      The purpose of the current study was to investigate if the protective effects of
      METH persisted for a long period of time. We also tested if a second challenge
      with a toxic dose of METH would cause further damage to monoaminergic terminals.
      Saline-pretreated rats showed significant METH-induced decreases in striatal DA
      and 5-HT levels in rats sacrificed 2 weeks after the challenge. Rats that
      received two METH challenges showed no further decreases in striatal DA or 5-HT
      levels in comparison to the single METH challenge. In contrast, METH-pretreated
      rats showed significant protection against METH-induced striatal DA and 5-HT
      depletion. In addition, the METH challenge causes substantial decreases in
      cortical 5-HT levels which were not further potentiated by a second drug
      challenge. METH preconditioning provided almost complete protection against METH 
      induced 5-HT depletion. These results are consistent with the idea that METH
      pretreatment renders the brain refractory to METH-induced degeneration of brain
      monoaminergic systems.

PMID- 21886559
TI  - Markers associated with sex differences in methamphetamine-induced striatal
      dopamine neurotoxicity.
AB  - Three different approaches were employed to assess various markers associated
      with sex differences in responses to methamphetamine (MA). Bioassay measures
      reveal that MA treatment results in significantly greater reductions in body
      weight and increases in body temperature in male mice. Protein and mRNA
      determinations show significant increases in Bcl-2 and PAI-1 in male mice, while
      females show significant increases in GFAP and decreases in IGF-1R following
      treatment with MA. In mice with a heterozygous mutation of their dopamine
      transporter (+/- DAT), only female mice show significant differences in dopamine
      transporter binding and mRNA and associated reductions in striatal dopamine
      content along with increases in MA-evoked striatal dopamine output. The
      identification of these sex-dependent differences in markers provides a
      foundation for more exhaustive evaluation of their impact upon, and treatment of,
      disorders/neurotoxicity of the nigrostriatal dopaminergic system and the bases
      for the differences that exist between females and males.

PMID- 21886560
TI  - May exercise prevent addiction?
AB  - Amphetamines exert their persistent addictive effects by activating brain's
      reward pathways, perhaps through the release of dopamine in the nucleus accumbens
      (and/or in other places). On the other hand, there is a relationship between
      dopamine and all behavioural aspects that involve motor activity and it has been
      demonstrated that exercise leads to an increase in the synthesis and release of
      dopamine, stimulates neuroplasticity and promotes feelings of well-being.
      Moreover, exercise and drugs of abuse activate overlapping neural systems. Thus,
      our aim was to study the influence of chronic exercise in the mechanism of
      addiction using an amphetamine-induced conditioned-place-preference in rats.Adult
      male Sprague-Dawley rats were randomly separated in groups with and without
      chronic exercise. Chronic exercise consisted in a 8 week treadmill running
      program, with increasing intensity. The conditioned place preference test was
      performed in both groups using a procedure and apparatus previously established.
      A 2 mg.kg(-1) amphetamine or saline solution was administered intraperitonially
      according to the schedule of the conditioned place preference. Before
      conditioning none of the animals showed preference for a specific compartment of
      the apparatus. The used amphetamine dose in the conditioning phase was able to
      produce a marked preference towards the drug-associated compartment in the group
      without exercise. In the animals with exercise a significant preference by the
      compartment associated with saline was observed. These results lead us to
      conclude that a previous practice of regular physical activity may help
      preventing amphetamine addiction in the conditions used in this test.

PMID- 21886562
TI  - Role of sigma receptors in methamphetamine-induced neurotoxicity.
AB  - Methamphetamine (METH) is a widely abused substance world over. Currently, there
      is no effective pharmacotherapy to treat its effects. This necessitates
      identification of potential novel therapeutic targets. METH interacts with sigma
      (sigma) receptors at physiologically relevant micromolar concentrations. In
      addition, sigma receptors are present in organs like the brain, heart, and lungs
      at which METH acts. Additionally, sigma receptors have been implicated in various
      acute and subchronic effects like locomotor stimulation, development of
      sensitization and neurotoxicity, where sigma receptor antagonists attenuate these
      effects. sigma Receptors may also have a role in METH-induced psychiatric
      complications such as depression, psychosis, cognitive and motor deficits. The
      neurotoxic effects of METH, which are cause for concern, can be prevented by
      sigma receptor antagonists in mice. Mechanistically, METH-induced neurotoxicity
      involves factors like dopamine release, oxidative stress, endoplasmic reticulum
      stress, activation of mitochondrial death cascades, glutamate release, apoptosis,
      microglial activation, and hyperthermia. This review compiles studies from the
      literature that suggests an important role for sigma receptors in many of the
      mechanisms of METH-induced neurotoxicity.

PMID- 21886561
TI  - Neuroprotective effect of resveratrol against methamphetamine-induced
      dopaminergic apoptotic cell death in a cell culture model of neurotoxicity.
AB  - A growing body of evidence suggests that oxidative stress-mediated cell death
      signaling mechanisms may exert neurotoxic effects of methamphetamine (MA)-induced
      dopaminergic neuronal loss. However, the means by which oxidative stress induced
      by MA causes neurodegeneration remains unclear. In recent years, resveratrol has
      garnered considerable attention owing to its antioxidant, anti-inflammatory, anti
      aging, and neuroprotective properties. In the present study, we sought to
      investigate the neuroprotective effects of resveratrol against apoptotic cell
      death in a mesencephalic dopaminergic neuronal cell culture model of MA
      neurotoxicity. MA treatment in the N27 dopaminergic neuronal cell model produced
      a time-dependent activation of the apoptotic cascade involving caspase-3 and DNA
      fragmentation. We found that the caspase-3 activation preceded DNA fragmentation.
      Notably, treatment with resveratrol almost completely attenuated MA-induced
      caspase-3 activity, but only partially reduced apoptotic cell death. We conclude
      that the neuroprotective effect of resveratrol is at least in part mediated by
      suppression of caspase-3 dependent cell death pathways. Collectively, our results
      demonstrate that resveratrol can attenuate MA-induced apoptotic cell death and
      suggest that resveratrol or its analogs may have therapeutic benefits in
      mitigating MA-induced dopaminergic neurodegeneration.

PMID- 21886563
TI  - Methylone and monoamine transporters: correlation with toxicity.
AB  - Methylone (2-methylamino-1-[3,4-methylenedioxyphenyl]propane-1-one) is a
      synthetic hallucinogenic amphetamine analog, like MDMA (3,4-methylenedioxy-
      methamphetamine), considered to act on monoaminergic systems. However, the
      psychopharmacological profile of its cytotoxicity as a consequence of
      monoaminergic deficits remains unclear. We examined here the effects of methylone
      on the transporters for dopamine (DAT), norepinephrine (NET), and serotonin
      (SERT), using a heterologous expression system in CHO cells, in association with
      its cytotoxicity. Methylone inhibited the activities of DAT, NET, and SERT, but
      not GABA transporter-1 (GAT1), in a concentration-dependent fashion with a rank
      order of NET > DAT > SERT. Methylone was less effective at inhibiting DAT and
      NET, but more effective against SERT, than was methamphetamine. Methylone alone
      was not toxic to cells except at high concentrations, but in combination with
      methamphetamine had a synergistic effect in CHO cells expressing the monoamine
      transporters but not in control CHO cells or cells expressing GAT1. The ability
      of methylone to inhibit monoamine transporter function, probably by acting as a
      transportable substrate, underlies the synergistic effect of methylone and
      methamphetamine.

PMID- 21886564
TI  - Decreases in brain reward function reflect nicotine- and methamphetamine
      withdrawal aversion in rats.
AB  - The purpose of the present study was to investigate whether brain reward function
      decreases during withdrawal from nicotine and methamphetamine, and whether
      decreased reward function is related to aversion during withdrawal from these
      drugs. For that purpose, male Sprague-Dawley rats were chronically infused
      subcutaneously with 9 mg/kg per day nicotine, or with 6 mg/kg per day
      methamphetamine using osmotic minipumps. In an intracranial self-stimulation
      (ICSS) paradigm, chronic infusion of nicotine and methamphetamine decreased the
      thresholds for lateral hypothalamic ICSS, whereas their antagonists, mecamylamine
      and haloperidol increased the ICSS thresholds in the rats treated with nicotine
      and methamphetamine, respectively. In a conditioned place aversion paradigm,
      mecamylamine and haloperidol produced place aversion in nicotine- and
      methamphetamine-infused rats, respectively. Interestingly, elevations in ICSS
      reward thresholds and place aversion during mecamylamine-precipitated nicotine
      withdrawal were almost the same in magnitude as those observed during haloperidol
      precipitated methamphetamine withdrawal. The present study indicates that 1)
      brain reward function decreased during nicotine and methamphetamine withdrawal,
      and 2) a decrease in reward function may reflect the negative affective state
      (aversion) during withdrawal from nicotine and methamphetamine.

PMID- 21886565
TI  - The Selective Serotonin Reuptake Inhibitor Paroxetine, but not Fluvoxamine,
      Decreases Methamphetamine Conditioned Place Preference in Mice.
AB  - Monoamine transporters are the main targets of methamphetamine (METH). Recently,
      we showed that fluoxetine, a selective serotonin reuptake inhibitor (SSRI),
      decreased METH conditioned place preference (CPP), suggesting that serotonin
      transporter (SERT) inhibition reduces the rewarding effects of METH. To further
      test this hypothesis, in the present study we investigated the effects of
      additional SSRIs, paroxetine and fluvoxamine, on METH CPP in C57BL/6J mice. In
      the CPP test, pretreatment with 20 mg/kg paroxetine abolished the CPP for METH,
      whereas pretreatment with 100 mg/kg fluvoxamine prior to administration of METH
      failed to inhibit METH CPP. These results suggest that paroxetine, a medication
      widely used to treat depression, may be a useful tool for treating METH
      dependence. Further, these data suggest that molecules other than the SERT [such
      as G protein-activated inwardly rectifying K+ (GIRK) channels] whose activities
      are modulated by paroxetine and fluoxetine, but not by fluvoxamine, are involved
      in reducing METH CPP by paroxetine and fluoxetine.

PMID- 21886566
TI  - MOP Reduction During Long-Term Methamphetamine Withdrawal was Restored by Chronic
      Post-Treatment with Fluoxetine.
AB  - Previously, we found fluoxetine reduces methamphetamine preference in mice.
      However, effects of fluoxetine on developed methamphetamine preference and on
      methamphetamine induced gene expression changes have been largely unknown. The
      present study investigates effects of post-treatment with fluoxetine on
      methamphetamine dependence and on gene expressions after long-term withdrawal in
      mice. First, we examined whether chronic post-treatment with fluoxetine
      attenuated methamphetamine-conditioned place preference. Next, we examined the
      changes in gene expression levels after long-term withdrawal (with saline or
      fluoxetine treatment) following chronic methamphetamine treatment. Using mRNA
      from the pooled frontal cortices of 10 mice per group, gene expression analyses
      were performed using a custom-developed cDNA array and a real-time quantitative
      reverse transcription-PCR. Chronic post-treatments with fluoxetine abolished the
      conditioned place preference developed by methamphetamine administrations. Even
      after long-term withdrawal from repeated methamphetamine administration, u-opioid
      receptor (MOP) gene expression was significantly reduced in the frontal cortex.
      The reduced MOP gene expression in the frontal cortex was restored by chronic
      administration with fluoxetine. These changes were confirmed by Western blot
      analyses. These findings suggest that the chronic post-treatments with fluoxetine
      might be effective for restoring the reduction of MOP levels in the frontal
      cortex following long-term abstinence from methamphetamine.

PMID- 21886567
TI  - Methamphetamine induces striatal cell death followed by the generation of new
      cells and a second round of cell death in mice.
AB  - Our laboratory has been investigating the impact of a neurotoxic exposure to
      methamphetamine (METH) on cellular components of the striatum post-synaptic to
      the dopaminergic terminals. A systemic bolus injection of METH (30 mg/kg, ip)
      induces the production of new cells in the striatum during a period lasting from
      24-48 hours after METH. The newly generated cells arise from dormant striatal
      progenitors and not from the subventricular zone. The newly generated cells
      display glial phenotypes and begin to die 24 hours after birth, or 2.5 days post
      METH. The protracted phase of cell death lasts for at least three months post
      METH at which time the bulk of the newly generated cells have disappeared. The
      METH-induced production of new cells is associated with enlarged striatal volume
      (up to 50% larger than controls in some animals). As the newly generated cells
      die over a period of three months, the enlarged striatal volume normalizes. In
      conclusion, a neurotoxic dose of METH induces the generation of new cells in the
      striatum associated with enlarged striatal volume. The new cells die over three
      months post-METH and the enlarged striatal volume returns to control levels. This
      observation is significant because studies involving METH users show striatal
      enlargement and the normalization of striatal volume in METH users who have been
      abstinent for up to 20 months.

PMID- 21886568
TI  - The Nature of 3, 4-Methylenedioxymethamphetamine (MDMA)-Induced Serotonergic
      Dysfunction: Evidence for and Against the Neurodegeneration Hypothesis.
AB  - High doses of the recreational drug 3,4-methylenedioxymethamphetamine (MDMA,
      "Ecstasy") have been well-documented to reduce the expression of serotonergic
      markers in several forebrain regions of rats and nonhuman primates. Neuroimaging
      studies further suggest that at least one of these markers, the plasma membrane
      serotonin transporter (SERT), may also be reduced in heavy Ecstasy users. Such
      effects, particularly when observed in experimental animal models, have generally
      been interpreted as reflecting a loss of serotonergic fibers and terminals
      following MDMA exposure. This view has been challenged, however, based on the
      finding that MDMA usually does not elicit glial cell reactions known to occur in
      response to central nervous system (CNS) damage. The aim of this review is to
      address both sides of the MDMA-neurotoxicity controversy, including recent
      findings from our laboratory regarding the potential of MDMA to induce
      serotonergic damage in a rat binge model. Our data add to the growing literature
      implicating neuroregulatory mechanisms underlying MDMA-induced serotonergic
      dysfunction and questioning the need to invoke a degenerative response to explain
      such dysfunction.

PMID- 21886569
TI  - Effects of MDMA on Extracellular Dopamine and Serotonin Levels in Mice Lacking
      Dopamine and/or Serotonin Transporters.
AB  - 3,4-Methylendioxymethamphetamine (MDMA) has both stimulatory and hallucinogenic
      properties which make its psychoactive effects unique and different from those of
      typical psychostimulant and hallucinogenic agents. The present study investigated
      the effects of MDMA on extracellular dopamine (DA(ex)) and serotonin (5-HT(ex))
      levels in the striatum and prefrontal cortex (PFC) using in vivo microdialysis
      techniques in mice lacking DA transporters (DAT) and/or 5-HT transporters (SERT).
      subcutaneous injection of MDMA (3, 10 mg/kg) significantly increased striatal
      DA(ex) in wild-type mice, SERT knockout mice, and DAT knockout mice, but not in
      DAT/SERT double-knockout mice. The MDMA-induced increase in striatal DA(ex) in
      SERT knockout mice was significantly less than in wildtype mice. In the PFC, MDMA
      dose-dependently increased DA(ex) levels in wildtype, DAT knockout, SERT knockout
      and DAT/SERT double-knockout mice to a similar extent. In contrast, MDMA markedly
      increased 5-HT(ex) in wildtype and DAT knockout mice and slightly increased 5
      HT(ex) in SERT-KO and DAT/SERT double-knockout mice. The results confirm that
      MDMA acts at both DAT and SERT and increases DA(ex) and 5-HT(ex).

PMID- 21886570
TI  - Enhanced Hyperthermia Induced by MDMA in Parkin Knockout Mice.
AB  - MDMA (3,4-methylenedioxymethamphetamine) is reportedly severely toxic to both
      dopamine (DA) and serotonin neurons. MDMA significantly reduces the number of DA
      neurons in the substantia nigra, but not in the nucleus accumbens, indicating
      that MDMA causes selective destruction of DA neurons in the nigrostriatal
      pathway, sparing the mesolimbic pathway. Parkinson's disease (PD) is a
      neurodegenerative disorder of multifactorial origin. The pathological hallmark of
      PD is the degeneration of DA neurons in the nigrostriatal pathway. Mutations in
      the parkin gene are frequently observed in autosomal recessive parkinsonism in
      humans. Parkin is hypothesized to protect against neurotoxic insult, and we
      attempted to clarify the role of parkin in MDMA-induced hyperthermia, one of the
      causal factors of neuronal damage, using parkin knockout mice. Body temperature
      was measured rectally before and 15, 30, 45, and 60 min after intraperitoneal
      injection of MDMA (30 mg/kg) at an ambient temperature of 22 +/- 2 degrees C.
      Significantly enhanced hyper-thermia after MDMA injection was observed in
      heterozygous and homozygous parkin knockout mice compared with wildtype mice,
      suggesting that parkin plays a protective role in MDMA neurotoxicity.

PMID- 21886571
TI  - Developing biomarkers for methamphetamine addiction.
AB  - There are an estimated 11.7 million methamphetamine (MA) abusers in the United
      States and epidemics of MA addiction are occurring worldwide. In our human
      laboratory and outpatient clinical trials we use innovative methods to quantify
      the severity of MA addiction and test biomarkers that may predict response to
      therapy or risk of relapse. One potential biomarker of addiction is the quantity
      of abused drug intake. Qualitative urinalysis is used in clinical trials and
      during treatment but provides only a binary outcome measure of abuse. Using non
      pharmacologic doses of deuterium labeled l-MA we have developed a continuous
      quantitative measure to estimate the bioavailable amount of MA addicts ingest.
      Brain Derived Neurotrophic Factor is a neurotrophin that encourages growth and
      differentiation of new neurons and synapses. Low BDNF levels are seen in many
      addictive disorders and BDNF is elevated in recovering MA addicts, suggesting
      BDNF may be a marker of MA addiction. We are investigating the effects of
      controlled doses of MA on BDNF levels and gene regulation and measuring BDNF in
      our clinical trials. We believe both patients and clinical researches will
      benefit from the addition of new, objective and quantifiable outcome measures
      that reflect disease severity and recovery from addiction.

PMID- 21886572
TI  - Roles of a novel molecule 'shati' in the development of methamphetamine-induced
      dependence.
AB  - The ability of drugs of abuse to cause dependence can be viewed as a form of
      neural plasticity. Recently, we have demonstrated that tumor necrosis factor
      alpha (TNF-alpha) increases dopamine uptake and inhibits methamphetamine-induced
      dependence. Moreover, we have identified a novel molecule 'shati' in the nucleus
      accumbens of mice treated with methamphetamine using the PCR-select cDNA
      subtraction method and clarified that it is involved in the development of
      methamphetamine dependence: Treatment with the shati antisense oligonucleotide
      (shati-AS), which inhibits the expression of shati mRNA, enhanced the
      methamphetamine-induced hyperlocomotion, sensitization, and conditioned place
      preference. Further, blockage of shati mRNA by shati-AS potentiated the
      methamphetamine-induced increase of dopamine overflow and the methamphetamine
      induced decrease in dopamine uptake in the nucleus accumbens. Interestingly,
      treatment with shati-AS also inhibited expression of TNF-alpha. Transfection of
      the vector containing shati cDNA into PC12 cells, dramatically induced the
      expression of shati and TNF-alpha mRNA, accelerated dopamine uptake, and
      inhibited the methamphetamine-induced decrease in dopamine uptake. These effects
      were blocked by neutralizing TNF-alpha. These results suggest that the functional
      roles of shati in methamphetamine-induced behavioral changes are mediated through
      the induction of TNF-alpha expression which inhibits the methamphetamine-induced
      increase of dopamine overflow and decrease in dopamine uptake.

PMID- 21886573
TI  - Pharmacologic Treatment with GABA(B) Receptor Agonist of Methamphetamine-Induced
      Cognitive Impairment in Mice.
AB  - Methamphetamine (METH) is a highly addictive drug, and addiction to METH has
      increased to epidemic proportions worldwide. Chronic use of METH causes
      psychiatric symptoms, such as hallucinations and delusions, and long-term
      cognitive deficits, which are indistinguishable from paranoid schizophrenia. The
      GABA receptor system is known to play a significant role in modulating the
      dopaminergic neuronal system, which is related to behavioral changes induced by
      drug abuse. However, few studies have investigated the effects of GABA receptor
      agonists on cognitive deficits induced by METH. In the present review, we show
      that baclofen, a GABA receptor agonist, is effective in treating METH-induced
      impairment of object recognition memory and prepulse inhibition (PPI) of the
      startle reflex, a measure of sensorimotor gating in mice. Acute and repeated
      treatment with METH induced a significant impairment of PPI. Furthermore,
      repeated but not acute treatment of METH resulted in a long-lasting deficit of
      object recognition memory. Baclofen, a GABA(B) receptor agonist, dose-dependently
      ameliorated the METH-induced PPI deficits and object recognition memory
      impairment in mice. On the other hand, THIP, a GABA(A) receptor agonist, had no
      effect on METH-induced cognitive deficits. These results suggest that GABA(B)
      receptors may constitute a putative new target in treating cognitive deficits in
      chronic METH users.

PMID- 21886574
TI  - Identification of selective agonists and antagonists to g protein-activated
      inwardly rectifying potassium channels: candidate medicines for drug dependence
      and pain.
AB  - G protein-activated inwardly rectifying K(+) (GIRK) channels have been known to
      play a key role in the rewarding and analgesic effects of opioids. To identify
      potent agonists and antagonists to GIRK channels, we examined various compounds
      for their ability to activate or inhibit GIRK channels. A total of 503 possible
      compounds with low molecular weight were selected from a list of fluoxetine
      derivatives at Pfizer Japan Inc. We screened these compounds by a Xenopus oocyte
      expression system. GIRK1/2 and GIRK1/4 heteromeric channels were expressed on
      Xenopus laevis oocytes at Stage V or VI. A mouse IRK2 channel, which is another
      member of inwardly rectifying potassium channels with similarity to GIRK
      channels, was expressed on the oocytes to examine the selectivity of the
      identified compounds to GIRK channels. For electrophysiological analyses, a two
      electrode voltage clamp method was used. Among the 503 compounds tested, one
      compound and three compounds were identified as the most effective agonist and
      antagonists, respectively. All of these compounds induced only negligible current
      responses in the oocytes expressing the IRK2 channel, suggesting that these
      compounds were selective to GIRK channels. These effective and GIRK-selective
      compounds may be useful possible therapeutics for drug dependence and pain.

PMID- 21886575
TI  - Gastrodia elata bl attenuates methamphetamine-induced dopaminergic toxicity via
      inhibiting oxidative burdens.
AB  - It has been recognized that Gastrodia elata Bl (GE), an oriental herb medicine,
      ameliorates various neurological disorders, that GE modulates the monoaminergic
      and GABAergic systems, and that GE possess antioxidant activities. We examined
      whether GE affects methamphetamine (MA)-induced striatal dopaminergic toxicity in
      mice. Treatment with MA (7.5 mg/kg, i.p. * 4) resulted in significant decreases
      in behavioural activity (as shown by locomotor activity and rota rod
      performance), dopamine level, tyrosine hydroxylase (TH) activity, and TH protein
      expression (as evaluated by immunocytochemistry and western blot analysis). In
      addition, MA treatment showed significant increases in lipid peroxidation [as
      evaluated by 4-hydroxy-2-nonenal (4-HNE) expression and malondialdehyde
      formation], protein oxidation (as shown by protein carbonyl expression and its
      formation), and reactive oxygen species (ROS) formation. Treatment with GE
      significantly attenuates MA-induced behavioural and dopaminergic impairments, and
      oxidative stresses in a dose-dependent manner. Our results suggest that GE
      treatment shows anti-dopaminergic effects in response to MA insult via, at least
      in part, inhibiting oxidative stresses in the striatum of the mice.

PMID- 21886576
TI  - Identifying changes in the synaptic proteome of cirrhotic alcoholic superior
      frontal gyrus.
AB  - Hepatic complications are a common side-effect of alcoholism. Without the
      detoxification capabilities of the liver, alcohol misuse induces changes in gene
      and protein expression throughout the body. A global proteomics approach was used
      to identify these protein changes in the brain. We utilised human autopsy tissue
      from the superior frontal gyrus (SFG) of six cirrhotic alcoholics, six alcoholics
      without comorbid disease, and six non-alcoholic non-cirrhotic controls. Synaptic
      proteins were isolated and used in two-dimensional differential in-gel
      electrophoresis coupled with mass spectrometry. Many expression differences were
      confined to one or other alcoholic sub-group. Cirrhotic alcoholics showed 99
      differences in protein expression levels from controls, of which half also
      differed from non-comorbid alcoholics. This may reflect differences in disease
      severity between the sub-groups of alcoholics, or differences in patterns of
      harmful drinking. Alternatively, the protein profiles may result from differences
      between cirrhotic and non-comorbid alcoholics in subjects' responses to alcohol
      misuse. Ten proteins were identified in at least two spots on the 2D gel; they
      were involved in basal energy metabolism, synaptic vesicle recycling, and
      chaperoning. These post-translationally modified isoforms were differentially
      regulated in cirrhotic alcoholics, indicating a level of epigenetic control not
      previously observed in this disorder.

PMID- 21886577
TI  - Association Analysis of Nuclear Receptor Rev-erb Alpha Gene (NR1D1) and Japanese
      Methamphetamine Dependence.
AB  - Several investigations suggested abnormalities in circadian rhythms are related
      to the pathophysiology of psychiatric disorders, including drug addiction.
      Recently, orphan nuclear receptor rev-erb alpha and glycogen synthase kinase-3
      beta (GSK-3beta) were shown to be important circadian components. In addition,
      the orphan nuclear receptor rev-erb alpha is a key negative feedback regulator of
      the circadian clock. These evidences indicate that rev-erb alpha gene (NR1D1) is
      a good candidate gene for the pathogenesis of methamphetamine dependence. To
      evaluate the association between NR1D1 and methamphetamine dependence, we
      conducted a case-control study of Japanese samples (215 methamphetamine
      dependence and 232 controls) with three tagging SNPs selected by HapMap database.
      Written informed consent was obtained from each subject. This study was approved
      by the ethics committees at Fujita Health University, Nagoya University Graduate
      School of Medicine and each participating member of the Institute of the Japanese
      Genetics Initiative for Drug Abuse (JGIDA). We did not detect an association
      between NR1D1 and Japanese methamphetamine dependence patients in allele/genotype
      wise analysis, or the haplotype analysis. Our findings suggest that NR1D1 does
      not play a major role in the pathophysiology of methamphetamine dependence in the
      Japanese population.

PMID- 21886578
TI  - Lack of association between prokineticin 2 gene and Japanese methamphetamine
      dependence.
AB  - Disruption of circadian rhythms may be involved in the pathophysiology of
      psychiatric disorders, including drug addiction. Recently, we detected the
      significant association between prokineticin 2 receptor gene (PROKR2) and
      Japanese methamphetamine dependence patients. Also, prokineticin 2 (PK2) gene
      deficient mice showed reduced physiological and behavioral parameters, including
      circadian locomotor activity, circulating glucocorticoid, glucose levels and the
      expression of peripheral clock genes compared with WT mice. These evidences
      indicate that PK2 gene (PROK2) is a good candidate gene for the pathogenesis of
      methamphetamine dependence. To evaluate the association between PROK2 and
      methamphetamine dependence, we conducted a case-control study of Japanese samples
      (215 methamphetamine dependence and 232 controls) with four tagging SNPs selected
      by HapMap database. The age and sex of the control subjects did not differ from
      those of the methamphetamine dependence patients. Written informed consent was
      obtained from each subject. This study was approved by the ethics committees at
      Fujita Health University, Nagoya University Graduate School of Medicine and each
      participating member of the Institute of the Japanese Genetics Initiative for
      Drug Abuse (JGIDA). We did not detect an association between PROK2 and Japanese
      methamphetamine dependence patients in allele/genotype-wise analysis, or the
      haplotype analysis. Our findings suggest that PROK2 does not play a major role in
      the pathophysiology of methamphetamine dependence in the Japanese population.

PMID- 21886579
TI  - Association analysis of the adenosine A1 receptor gene polymorphisms in patients
      with methamphetamine dependence/psychosis.
AB  - Several lines of evidence suggest that the dopaminergic nervous system
      contributes to methamphetamine (METH) dependence, and there is increasing
      evidence of antagonistic interactions between dopamine and adenosine receptors in
      METH abusers. We therefore hypothesized that variations in the A1 adenosine
      receptor (ADORA1) gene modify genetic susceptibility to METH
      dependence/psychosis. In this study, we identified 7 single nucleotide
      polymorphisms (SNPs) in exons and exon-intron boundaries of the ADORA1 gene in a
      Japanese population. A total of 171 patients and 229 controls were used for an
      association analysis between these SNPs and METH dependence/psychosis. No
      significant differences were observed in either the genotypic or allelic
      frequencies between METH dependent/psychotic patients and controls. A global test
      of differentiation among samples based on haplotype frequencies showed no
      significant association. In the clinical feature analyses, no significant
      associations were observed among latency of psychosis, prognosis of psychosis,
      and spontaneous relapse. These results suggest that the ADORA1 gene variants may
      make little or no contribution to vulnerability to METH dependence/psychosis.

PMID- 21886581
TI  - Genetic Association Analysis of NOS3 and Methamphetamine-Induced Psychosis Among
      Japanese.
AB  - Endothelial nitric oxide synthase (NOS3) is one of the enzymes influencing nitric
      oxide (NO) function in the human brain. NO is a gaseous neurotransmitter that is
      involved in a variety of mechanisms in the central nervous system, such as N
      methyl-D-aspartate receptor activation and oxidative stress. The evidence from
      animal pharmacological studies and postmortem studies supports an association
      between NO and psychotic disorders. Methamphetamine (METH) use disorder is a
      known psychotic disorder, and we therefore conducted a gene-based case-control
      study between tagging single nucleotide polymorphisms (SNPs) (rs2070744,
      rs1799983) in NOS3 and METH-induced psychosis in Japanese subjects (183 with METH
      induced psychosis and 267 controls). Written informed consent was obtained from
      each subject. No significant association was found between any tagging SNP in
      NOS3 and METH-induced psychosis in the allele/genotype-wise or haplotype-wise
      analyses. In conclusion, we suggest that NOS3 might not contribute to the risk of
      METH-induced psychosis in the Japanese population.

PMID- 21886580
TI  - Differential gene expression in the nucleus accumbens and frontal cortex of lewis
      and Fischer 344 rats relevant to drug addiction.
AB  - Drug addiction results from the interplay between social and biological factors.
      Among these, genetic variables play a major role. The use of genetically related
      inbred rat strains that differ in their preference for drugs of abuse is one
      approach of great importance to explore genetic determinants. Lewis and Fischer
      344 rats have been extensively studied and it has been shown that the Lewis
      strain is especially vulnerable to the addictive properties of several drugs when
      compared with the Fischer 344 strain. Here, we have used microarrays to analyze
      gene expression profiles in the frontal cortex and nucleus accumbens of Lewis and
      Fischer 344 rats. Our results show that only a very limited group of genes were
      differentially expressed in Lewis rats when compared with the Fischer 344 strain.
      The genes that were induced in the Lewis strain were related to oxygen transport,
      neurotransmitter processing and fatty acid metabolism. On the contrary genes that
      were repressed in Lewis rats were involved in physiological functions such as
      drug and proton transport, oligodendrocyte survival and lipid catabolism.These
      data might be useful for the identification of genes which could be potential
      markers of the vulnerability to the addictive properties of drugs of abuse.

PMID- 21886582
TI  - Genetic Association Analysis of NOS1 and Methamphetamine-Induced Psychosis Among
      Japanese.
AB  - The neuronal nitric oxide synthase gene (NOS1) is located at 12q24, a
      susceptibility region for schizophrenia, and produces nitric oxide (NO). NO has
      been reported to play important roles as a gaseous neurotransmitter in brain. NO
      is a second messenger for the N-methyl-D aspartate (NMDA) receptor and is related
      to the dopaminergic system. Because the symptomatology of methamphetamine (METH)
      use disorder patients with psychosis is similar to that of patients with
      schizophrenia, NOS1 is a good candidate gene for METH-induced psychosis.
      Therefore, we conducted a case-control association study between NOS1 and METH
      induced psychosis with Japanese subjects (183 with METH-induced psychosis
      patients and 519 controls). We selected seven SNPs (rs41279104, rs3782221,
      rs3782219, rs561712, rs3782206, rs6490121, rs2682826) in NOS1 from previous
      reports. Written informed consent was obtained from each subject. This study was
      approved by the Ethics Committee at Fujita Health University School of Medicine
      and each participating institute of the Japanese Genetics Initiative for Drug
      Abuse (JGIDA). No significant association was found between NOS1 and METH-induced
      psychosis in the allele/genotype-wise or haplotype-wise analyses. In conclusion,
      we suggest that NOS1 might not contribute to the risk of METH-induced psychosis
      in the Japanese population.

PMID- 21886583
TI  - No Association Between GRM3 and Japanese Methamphetamine-Induced Psychosis.
AB  - Several investigations have suggested that abnormalities in glutamate neural
      transmission play a role in the pathophysiology of psychiatric disorders,
      including schizophrenia. The metabotropic glutamate 3 receptor (mGluR3) gene was
      reported to be associated with schizophrenia, and paranoid type schizophrenia has
      symptoms that are similar to those of methamphetamine-induced psychosis. This
      suggests that mGluR3 gene (GRM3) is a good candidate gene for the pathogenesis of
      methamphetamine-induced psychosis. To evaluate the association between GRM3 and
      methamphetamine-induced psychosis, we conducted a case-control study of Japanese
      samples (181 methamphetamine-induced psychosis and 232 controls). METHODS: We
      selected one functional SNP (rs6465084), reported to be associated with
      prefrontal brain functioning, for an association analysis. Written informed
      consent was obtained from each subject. This study was approved by the ethics
      committees at Fujita Health University, Nagoya University Graduate School of
      Medicine and each participating member of the Institute of the Japanese Genetics
      Initiative for Drug Abuse (JGIDA). RESULTS: We did not detect an association
      between rs6465084 in GRM3 and Japanese methamphetamine-induced psychosis.
      CONCLUSION: Our findings suggest that rs6465084 in GRM3 does not play a major
      role in the pathophysiology of methamphetamine-induced psychosis in the Japanese
      population. However, because we did not perform an association analysis based on
      linkage disequilibrium (LD) or a mutation scan of GRM3, a replication study using
      a larger sample and based on LD may be required for conclusive results.

PMID- 21886584
TI  - Association Between 5HT1b Receptor Gene and Methamphetamine Dependence.
AB  - Several lines of evidence implicate serotonergic dysfunction in diverse
      psychiatric disorders including anxiety, depression, and drug abuse. Mice with a
      knock-out of the 5HT1b receptor gene (HTR1B) displayed increased locomotor
      response to cocaine and elevated motivation to self-administer cocaine and
      alcohol. Previous genetic studies showed significant associations of HTR1B with
      alcohol dependence and substance abuse, but were followed by inconsistent
      results. We examined a case-control genetic association study of HTR1B with
      methamphetamine-dependence patients in a Japanese population. The subjects were
      231 patients with methamphetamine dependence, 214 of whom had a co-morbidity of
      methamphetamine psychosis, and 248 age- and sex-matched healthy controls. The
      three single nucleotide polymorphisms (SNPs), rs130058 (A-165T), rs1228814 (A
      700C) and rs1228814 (A+1180G) of HTR1B were genotyped. There was no significant
      difference in allelic and genotypic distributions of the SNPs between
      methamphetamine dependence and the control. Genetic associations of HTR1B were
      tested with several clinical phenotypes of methamphetamine dependence and/or
      psychosis, such as age at first abuse, duration of latency from the first abuse
      to onset of psychosis, prognosis of psychosis after therapy, and complication of
      spontaneous relapse of psychotic state. There was, however, no asscocation
      between any SNP and the clinical phenotypes. Haplotype analyses showed the three
      SNPs examined were within linkage disequilibrium, which implied that the three
      SNPs covered the whole HTR1B, and distribution of estimated haplotype frequency
      was not different between the groups. The present findings may indicate that
      HTR1B does not play a major role in individual susceptibility to methamphetamine
      dependence or development of methamphetamine-induced psychosis.

PMID- 21886585
TI  - Association study of serine racemase gene with methamphetamine psychosis.
AB  - Experimental studies have demonstrated that not only dopaminergic signaling but
      also glutamatergic/NMDA receptor signaling play indispensable roles in the
      development of methamphetamine psychosis. Our recent genetic studies provided
      evidence that genetic variants of glutamate-related genes such as DTNBP1, GLYT1,
      and G72, which are involved in glutamate release and regulation of co-agonists
      for NMDA receptors, conferred susceptibility to methamphetamine psychosis. Serine
      racemase converts l-serine to d-serine, which is an endogenous co-agonist for
      NMDA receptors. Three single nucleotide polymorphisms (SNPs) in the promoter
      region of the serine racemase gene (SRR), rs224770, rs3760229, and rs408067, were
      proven to affect the transcription activity of SRR. Therefore, we examined these
      SNPs in 225 patients with methamphetamine psychosis and 291 age- and sex-matched
      controls. There was no significant association between methamphetamine psychosis
      and any SNP examined or between the disorder and haplotypes comprising the three
      SNPs. However, rs408067 was significantly associated with the prognosis for
      methamphetamine psychosis and multi-substance abuse status. The patients with C
      positive genotypes (CC or CG) of rs408067 showed better prognosis of psychosis
      after therapy and less abuse of multiple substances than the patients with GG
      genotypes. Because the C allele of rs408067 reduces the expression of SRR, a
      lower d-serine level or reduced NMDA receptor activation may affect the prognosis
      of methamphetamine psychosis and multiple substance abuse. Our sample size is,
      however, not large enough to eliminate the possibility of a type I error, our
      findings must be confirmed by replicate studies with larger samples.

PMID- 21886587
TI  - Association Study of Two Cannabinoid Receptor Genes, CNR1 and CNR2, with
      Methamphetamine Dependence.
AB  - Several studies have suggested that the endocannabinoid system plays significant
      roles in the vulnerability to psychiatric disorders including drug abuse. To
      examine the possible association of the CNR1 and CNR2 genes, which encode
      cannabinoid receptors CB1 and CB2, with methamphetamine dependence, we
      investigated three single nucleotide polymorphisms (SNPs) (rs806379, rs1535255,
      rs2023239) in intron 2 of the CNR1 gene and a nonsynonymous SNP, Q63R, in the
      CNR2 gene. The study samples consisted of 223 patients with methamphetamine
      dependence and 292 age- and sex- matched controls. There were no significant
      differences between the patients and controls in genotypic or allelic
      distribution of any SNP of the CNR1 and CNR2 genes. We also analyzed the clinical
      features of methamphetamine dependence. Rs806379 of the CNR1 gene showed a
      significant association with the phenotype of latency of psychosis after the
      first consumption of methamphetamine. Patients with the T allele or T-positive
      genotypes (T/T or A/T) may develop a rapid onset of psychosis after
      methamphetamine abuse. The present study suggests a possibility that genetic
      variants of the CNR1 gene may produce a liability to the complication of
      psychotic state after abuse of methamphetamine; however, our findings need to be
      confirmed by future replications.

PMID- 21886586
TI  - Association analysis of the tryptophan hydroxylase 2 gene polymorphisms in
      patients with methamphetamine dependence/psychosis.
AB  - There is a growing evidence that serotoninergic systems modulate dopaminergic
      neurotransmission. We analyzed the association between the variations in the
      brain tryptophan hydroxylase 2 (TPH2) gene, a rate limiting enzyme for serotonin
      biosynthesis, and methamphetamine (METH) dependence/psychosis in a Japanese
      population. We found ten single nucleotide polymorphisms (SNPs) and two
      polynucleotide polymorphisms in TPH2 gene exons and exon-intron boundaries. A
      total of 162 patients and 243 controls were used for the association analysis
      between these polymorphisms and METH dependence/psychosis. No significant
      differences were observed in either genotypic or allelic frequencies between METH
      dependent/psychotic patients and controls. A global test of differentiation among
      samples based on haplotype frequencies showed no significant association. With
      respect to latency of psychosis, prognosis of psychosis, and spontaneous relapse,
      we found no significant association with these SNPs. These results suggest that
      the TPH2 gene variants may not be a factor in vulnerability to METH
      dependence/psychosis.

PMID- 21886588
TI  - Association between the Regulator of G-protein Signaling 9 Gene and Patients with
      Methamphetamine Use Disorder and Schizophrenia.
AB  - The regulator of G-protein signaling (RGS) modulates the functioning of
      heterotrimeric G protein. RGS9-2 is highly expressed in the striatum and plays a
      role in modulating dopaminergic receptor-mediated signaling cascades. Previous
      studies suggested that the RGS9 gene might contribute to the susceptibility to
      psychotic diseases. Therefore, we investigated the association between the RGS9
      gene and two related dopamine psychoses, schizophrenia and methamphetamine use
      disorders. The subjects comprised 487 patients of schizophrenia and 464 age- and
      sex-matched healthy controls and 220 patients of methamphetamine use disorder and
      289 controls. We genotyped two nonsynonymous polymorphisms, rs12452285
      (Leu225Ser) and rs34797451 (His498Arg), of the RGS9 gene. Rs34797451 showed
      monomorphism in the present Japanese population, but rs12452285 showed
      polymorphism. There were no significant differences in genotypic or allelic
      distributions of rs12452285 between patients with schizophrenia and the
      corresponding control or between patients with methamphetamine use disorder and
      the corresponding control. We also analyzed the clinical features of
      methamphetamine use disorder. We found a significant association in allelic
      distribution with the phenotypes of age at first consumption (p=0.047). The
      present study suggested that the RGS9 gene is unlikely to play a major role in
      schizophrenia and methamphetamine dependence liability and/or the development of
      methamphetamine induced psychosis, at least in a Japanese population.

PMID- 21886589
TI  - Acetyl-L-Carnitine Modulates TP53 and IL10 Gene Expression Induced by 3-NPA
      Evoked Toxicity in PC12 Cells.
AB  - The neurotoxicity induced by the mitochondrial inhibitor 3-nitropropionic acid (3
      NPA) is associated with a decrease of ATP synthesis and an increase of free
      radical production which can lead to apoptosis or necrosis. We have used the
      PC12, neuron-like rat pheochromocytoma cell line, to study further the mechanism
      of 3-NPA-evoked neurotoxicity and the effects of acetyl-L-carnitine (ALC) which
      has neuroprotective actions against various types of mitochondrial
      inhibitors.Cultured PC 12 cells were exposed to a low dose of 3-NPA 50 (microM)
      in the presence or absence of 5 mM ALC. The dose of 3-NPA was sub toxic and no
      changes in pro-apoptotic Bax or anti-apoptotic Bcl-2 gene expression were
      observed. We followed specific genetic markers to look for changes evoked by 3
      NPA toxicity and also changes associated with neuroprotection exerted by the ALC
      treatment, using RT-PCR arrays (delta-delta method). 3-NPA exposure evoked a
      decrease in expression of the Tp53 gene. This down regulation was prevented by
      pretreatment of the cells with ALC. The Tp53 gene responds to cellular stresses
      and the effects seen here are possibly associated with the 3-NPA evoked changes
      in mitochondrial metabolism. Other genes associated with stress and apoptosis,
      Parp-1, Bcl-2, and Bax were not affected by 3-NPA or ALC. The decrease of
      inflammatory response Il-10 gene expression due to 3-NPA was further lowered by
      presence of ALC. Other inflammation related genes, Il1rn, Nr3c1 and Cxcr4 were
      not affected. Interestingly, the glutamate transporter slc17a7, carnitine
      acylcarnitine translocase Slc25a20 and heat shock proteins genes, Hsp27, Hmox1
      (Hsp32, HO1) as well as Hspa 1a (Hsp 70) increased only when both ALC and small
      dose of 3-NPA were present. The alterations in gene expression detected in this
      study suggest role of several intracellular pathways in the neurotoxicity of 3
      NPA and the neuroprotection against 3-NPA-induced neurotoxicity by ALC.

PMID- 21886590
TI  - Altered Mesolimbic Dopamine System in THC Dependence.
AB  - To explore the functional consequences of cannabinoid withdrawal in the rat
      mesolimbic dopamine system, we investigated the anatomical morphology of the
      mesencephalic, presumed dopaminergic, neurons and their main post-synaptic target
      in the Nucleus Accumbens. We found that TH-positive neurons shrink and Golgi
      stained medium spiny neurons loose dendritic spines in withdrawal rats after
      chronic cannabinoids administration. Similar results were observed after
      administration of the cannabinoid antagonist rimonabant to drug-naive rats
      supporting a role for endocannabinoids in neurogenesis, axonal growth and
      synaptogenesis. This evidence supports the tenet that withdrawal from addictive
      compounds alters functioning of the mesolimbic system. The data add to a growing
      body of work which indicates a hypodopaminergic state as a distinctive feature of
      the "addicted brain".

PMID- 21886591
TI  - Commentary: Functional Neuronal CB2 Cannabinoid Receptors in the CNS.
AB  - Cannabinoids are the constituents of the marijuana plant (Cannabis sativa). There
      are numerous cannabinoids and other natural compounds that have been reported in
      the cannabis plant. The recent progress in marijuana-cannabinoid research include
      the discovery of an endocannabinoid system with specific genes coding for
      cannabinoid receptors (CBRs) that are activated by smoking marijuana, and that
      the human body and brain makes its own marijuana-like substances called
      endocannabinoids that also activate CBRs. This new knowledge and progress about
      cannabinoids and endocannabinoids indicate that a balanced level of
      endocannabinoids is important for pregnancy and that the breast milk in animals
      and humans has endocannabinoids for the growth and development of the new born.
      There are two well characterized cannabinoid receptors termed CB1-Rs and CB2-Rs
      and these CBRs are perhaps the most abundant G-protein coupled receptors that are
      expressed at high levels in many regions of the mammalian brain. The expression
      of CB1-Rs in the brain and periphery and the identification of CB2-Rs in immune
      cells and during inflammation has been extensively studied and characterized.
      However, the expression of functional neuronal CB2-Rs in the CNS has been much
      less well established and characterized in comparison to the expression of
      abundant brain CB1-Rs and functional neuronal CB2-Rs has ignited debate and
      controversy. While the issue of the specificity of CB2-R antibodies remains, many
      recent studies have reported the discovery and functional characterization of
      functional neuronal CB2-Rs in the CNS beyond neuro-immuno cannabinoid activity.

PMID- 21886592
TI  - Consequences of cannabinoid and monoaminergic system disruption in a mouse model
      of autism spectrum disorders.
AB  - Autism spectrum disorders (ASDs) are heterogenous neurodevelopmental disorders
      characterized by impairment in social, communication skills and stereotype
      behaviors. While autism may be uniquely human, there are behavioral
      characteristics in ASDs that can be mimicked using animal models. We used the
      BTBR T+tf/J mice that have been shown to exhibit autism-like behavioral
      phenotypes to 1). Evaluate cannabinoid-induced behavioral changes using forced
      swim test (FST) and spontaneous wheel running (SWR) activity and 2). Determine
      the behavioral and neurochemical changes after the administration of MDMA (20
      mg/kg), methamphetamine (10 mg/kg) or MPTP (20 mg/kg). We found that the BTBR
      mice exhibited an enhanced basal spontaneous locomotor behavior in the SWR test
      and a reduced depressogenic profile. These responses appeared to be enhanced by
      the prototypic cannabinoid, Delta(9)-THC. MDMA and MPTP at the doses used did not
      modify SWR behavior in the BTBR mice whereas MPTP reduced SWR activity in the
      control CB57BL/6J mice. In the hippocampus, striatum and frontal cortex, the
      levels of DA and 5-HT and their metabolites were differentially altered in the
      BTBR and C57BL/6J mice. Our data provides a basis for further studies in
      evaluating the role of the cannabinoid and monoaminergic systems in the etiology
      of ASDs.

PMID- 21886593
TI  - Involvement of u-Opioid Receptor in Methamphetamine-Induced Behavioral
      Sensitization.
AB  - Methamphetamine is a potent addictive stimulant drug that activates certain
      systems in the brain. It is a member of the amphetamine family, but the effects
      of methamphetamine are much more potent, longer lasting, and more harmful to the
      central nervous system. Repeated administration of methamphetamine induces
      behavioral sensitization, which is considered to be related to compulsive drug
      seeking behavior. Although the mechanism responsible for methamphetamine-induced
      behavioral sensitization remains unclear, it is believed that the mesolimbic
      dopaminergic system in the central nervous system plays a critical role in the
      development of behavioral sensitization. Our previous studies indicate that the
      involvement of the MU-opioid receptor system underlies the development of
      methamphetamine-induced behavioral sensitization. Understanding the mechanisms of
      behavioral sensitization that are regulated by the MU-opioid receptor system
      would be helpful in developing therapeutic programs against methamphetamine
      addiction. This review briefly discusses the neural circuitry and cellular
      mechanisms that are known to play a central role in methamphetamine-induced
      behavioral sensitization and outlines the role of the MU-opioid receptor system
      in the development of methamphetamine-induced sensitization.

PMID- 21886594
TI  - Quantitative Detection of u Opioid Receptor: Western Blot Analyses Using u Opioid
      Receptor Knockout Mice.
AB  - Increasing evidence suggests that u opioid receptor (MOP) expression is altered
      during the development of and withdrawal from substance dependence. Although anti
      MOP antibodies have been hypothesized to be useful for estimating MOP expression
      levels, inconsistent MOP molecular weights (MWs) have been reported in studies
      using anti-MOP antibodies. In the present study, we generated a new anti-MOP
      antibody (N38) against the 1-38 amino acid sequence of the mouse MOP N-terminus
      and conducted Western blot analysis with wildtype and MOP knockout brain lysates
      to determine the MWs of intrinsic MOP. The N38 antibody detected migrating bands
      with relative MWs of 60-67 kDa in the plasma membrane fraction isolated from
      wildtype brain, but not from the MOP knockout brain. These migrating bands
      exhibited semi-linear density in the range of 3-30 ug membrane proteins/lane. The
      N38 antibody may be useful for quantitatively detecting MOP.

PMID- 21886596
TI  - Analysis of electrical brain waves in neurotoxicology: gamma-hydroxybutyrate.
AB  - Advances in computer technology have allowed quantification of the
      electroencephalogram (EEG) and expansion of quantitative EEG (qEEG) analysis in
      neurophysiology, as well as clinical neurology, with great success. Among the
      variety of techniques in this field, frequency (spectral) analysis using Fast
      Fourier Transforms (FFT) provides a sensitive tool for time-course studies of
      different compounds acting on particular neurotransmitter systems. Studies
      presented here include Electrocorticogram (ECoG) analysis following exposure to a
      glutamic acid analogue - domoic acid (DOM), psychoactive indole alkaloid -
      ibogaine, as well as cocaine and gamma-hydroxybutyrate (GHB). The ECoG was
      recorded in conscious rats via a tether and swivel system. The EEG signal
      frequency analysis revealed an association between slow-wave EEG activity delta
      and theta and the type of behavioral seizures following DOM administration.
      Analyses of power spectra obtained in rats exposed to cocaine alone or after
      pretreatment with ibogaine indicated the contribution of the serotonergic system
      in ibogaine mediated response to cocaine (increased power in alpha(1) band).
      Ibogaine also lowered the threshold for cocaine-induced electrographic seizures
      (increased power in the low-frequency bands, delta and theta). Daily
      intraperitoneal administration of cocaine for two weeks was associated with a
      reduction in slow-wave ECoG activity 24 hrs following the last injection when
      compared with controls. Similar decreased cortical activity in low-frequency
      bands observed in chronic cocaine users has been associated with reduced
      metabolic activity in the frontal cortex. The FFT analyses of power spectra
      relative to baseline indicated a significant energy increase over all except
      beta(2) frequency bands following exposure to 400 and 800 mg/kg GHB. The EEG
      alterations detected in rats following exposure to GHB resemble absence seizures
      observed in human petit mal epilepsy. Spectral analysis of the EEG signals
      combined with behavioral observations may prove to be a useful approach in
      studying chronic exposure to drugs of abuse and treatment of drug dependence.

PMID- 21886595
TI  - Cerebrolysin Attenuates Heat Shock Protein (HSP 72 KD) Expression in the Rat
      Spinal Cord Following Morphine Dependence and Withdrawal: Possible New Therapy
      for Pain Management.
AB  - The possibility that pain perception and processing in the CNS results in
      cellular stress and may influence heat shock protein (HSP) expression was
      examined in a rat model of morphine dependence and withdrawal. Since activation
      of pain pathways result in exhaustion of growth factors, we examined the
      influence of cerebrolysin, a mixture of potent growth factors (BDNF, GDNF, NGF,
      CNTF etc,) on morphine induced HSP expression. Rats were administered morphine
      (10 mg/kg, s.c. /day) for 12 days and the spontaneous withdrawal symptoms were
      developed by cessation of the drug administration on day 13(th) that were
      prominent on day 14(th) and continued up to day 15(th) (24 to 72 h periods). In a
      separate group of rats, cerebrolysin was infused intravenously (5 ml/kg) once
      daily from day one until day 15(th). In these animals, morphine dependence and
      withdrawal along with HSP immunoreactivity was examined using standard protocol.
      In untreated group mild HSP immunoreaction was observed during morphine
      tolerance, whereas massive upregulation of HSP was seen in CNS during withdrawal
      phase that correlated well with the withdrawal symptoms and neuronal damage.
      Pretreatment with cerebrolysin did not affect morphine tolerance but reduced the
      HSP expression during this phase. Furthermore, cerebrolysin reduced the
      withdrawal symptoms on day 14(th) to 15(th). Taken together these observations
      suggest that cellular stress plays an important role in morphine induced pain
      pathology and exogenous supplement of growth factors, i.e. cerebrolysin
      attenuates HSP expression in the CNS and induce neuroprotection. This indicates a
      new therapeutic role of cerebrolysin in the pathophysiology of drugs of abuse,
      not reported earlier.

PMID- 21886598
TI  - Inhibition of g protein-activated inwardly rectifying k channels by
      phencyclidine.
AB  - Addictive drugs, such as opioids, ethanol, cocaine, amphetamine, and
      phencyclidine (PCP), affect many functions of the nervous system and peripheral
      organs, resulting in severe health problems. G protein-activated inwardly
      rectifying K(+) (GIRK, Kir3) channels play an important role in regulating
      neuronal excitability through activation of various Gi/o protein-coupled
      receptors including opioid and CB(1) cannabinoid receptors. Furthermore, the
      channels are directly activated by ethanol and inhibited by cocaine at toxic
      levels, but not affected by methylphenidate, methamphetamine, and 3,4
      methylenedioxymethamphetamine (MDMA) at toxic levels. The primary pharmacological
      action of PCP is blockade of N-methyl-D-aspartate (NMDA) receptor channels that
      are associated with its psychotomimetic effects. PCP also interacts with several
      receptors and channels at relatively high concentrations. However, the molecular
      mechanisms underlying the various effects of PCP remain to be clarified. Here, we
      investigated the effects of PCP on GIRK channels using the Xenopus oocyte
      expression system. PCP weakly but significantly inhibited GIRK channels at
      micromolar concentrations, but not Kir1.1 and Kir2.1 channels. The PCP
      concentrations effective in inhibiting GIRK channels overlap clinically relevant
      brain concentrations in severe intoxication. The results suggest that partial
      inhibition of GIRK channels by PCP may contribute to some of the toxic effects
      after overdose.

PMID- 21886597
TI  - GHB-Induced Cognitive Deficits During Adolescence and the Role of NMDA Receptor.
AB  - We have earlier reported that gamma-hydroxybutyric acid (GHB) disrupts the
      acquisition of spatial learning and memory in adolescent rats. GHB is known to
      interact with several neurotransmitter systems that have been implicated in
      cognitive functioning. The N-methyl-D-aspartate receptor (NR) -type of glutamate
      receptor is considered to be an important target for spatial learning and memory.
      Molecular mechanisms governing the neuroadptations following repeated GHB
      treatment in adolecent rats remain unknown. We examined the role of NMDA receptor
      in adolescent GHB-induced cognitive deficit. Adolescent rats were administered
      with GHB on 6 consecutive days, and surface-expressed NMDA receptor subunits
      levels were measured. GHB significantly decreased NR1 levels in the frontal
      cortex. Adolescent GHB also significantly reduced cortical NR2A subunit levels.
      Our findings support the hypothesis that adolescent GHB-induced cogntive deficits
      are associated with neuroadaptations in glutamatergic transmission, particulaly
      NR functioning in the frontal cortex.

PMID- 21886599
TI  - Effects of gastrodia elata bl on phencyclidine-induced schizophrenia-like
      psychosis in mice.
AB  - It has been demonstrated that 5-HT(1A) receptors play an important role in the
      pathophysiology of schizophrenia. Because Gastrodia elata Bl (GE) modulates the
      serotonergic system, we examined whether GE could affect phencyclidine (PCP)
      induced abnormal behavior in mice. Repeated treatment with PCP increased
      immobility time, while it decreased social interaction time and recognition
      memory. PCP-induced abnormal behaviors were significantly attenuated by GE, and
      these effects were comparable to those of 8-OH-DPAT, a 5-HT(1A) receptor agonist.
      Furthermore, GE-mediated effects were counteracted by WAY 100635, a 5-HT(1A)
      receptor antagonist. Our results suggest that the antipsychotic effects of GE
      are, at least in part, mediated via activation of 5-HT(1A) in mice.

PMID- 21886600
TI  - Impaired spatial memory after ketamine administration in chronic low doses.
AB  - Ketamine is a noncompetitive antagonist of the NMDA-receptors, used as a
      dissociative anesthetic, presently included in the category of the psychoactive
      substances known as "club drugs". Ketamine administration was associated with
      impaired working memory and increased psychopathological symptoms, but there is a
      lack of information regarding the effects of chronic sub-anesthetic doses. Adult
      Wistar rats were administered ketamine, 5 and 10 mg/kg twice daily,
      subcutaneously for 14 days. One week later, rats were tested in an object
      recognition/object location task and in the open field arena. There was altered
      performance in both the object recognition/location and in the open field tests
      by the group chronically exposed to the lower dose of ketamine. These animals
      displayed a decreased discrimination index (p<0.05) in the object recognition
      task, were unable to recognize the displacement of a familiar object and
      displayed decreased activity across open filed sessions. Importantly, these
      alterations were not observed in animals administered a higher dose of ketamine.
      Collectively, these results consistently show that chronic administration of
      ketamine in sub-anesthetic doses may lead to decreased habituation and inability
      to update spatial representations.

PMID- 21886601
TI  - Ketamine-induced neurotoxicity and changes in gene expression in the developing
      rat brain.
AB  - Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used for
      analgesia and anesthesia in obstetric and pediatric practice. Recent reports
      indicate that ketamine causes neuronal cell death in developing rodents and
      nonhuman primates. The present study assessed the potential dose- and time
      dependent neurotoxic effects and associated changes in gene expression after
      ketamine administration to postnatal day 7 (PND-7) rat pups. Pups were exposed to
      ketamine subcutaneously at doses of 5, 10, or 20 mg/kg, in one, three or six
      injections respectively. Control animals received the same volume of saline at
      the same time points. The animals were sacrificed 6 h after the last ketamine or
      saline administration and brain tissues were collected for RNA isolation and
      histochemical examination. Six injections of 20 mg/kg ketamine significantly
      increased neuronal cell death in frontal cortex, while lower doses and fewer
      injections did not show significant effects. The ketamine induced cell death
      seemed to be apoptotic in nature. In situ hybridization demonstrated that NMDA
      receptor NR1 subunit expression was dramatically increased in the frontal cortex
      of ketamine treated rats. Microarray analysis revealed altered expression of
      apoptotic relevant genes and increased NMDA receptor gene expression in brains
      from ketamine treated animals. Quantitative RT-PCR confirmed the microarray
      results. These data suggest that repeated exposures to high doses of ketamine can
      cause compensatory up-regulation of NMDA receptors and subsequently trigger
      apoptosis in developing neurons.

PMID- 21886603
TI  - A Copper Binding Site within the Pathological Conformer Epitope of Mutant SOD1.

PMID- 21886602
TI  - microRNAs, Gap Junctional Intercellular Communication and Mesenchymal Stem Cells
      in Breast Cancer Metastasis.
AB  - The failed outcome of autologous bone marrow transplantation for breast cancer
      opens the field for investigations. This is particularly important because the
      bone marrow could be a major source of cancer cells during tertiary metastasis.
      This review discusses subsets of breast cancer cells, including those that enter
      the bone marrow at an early period of disease development, perhaps prior to
      clinical detection. This population of cells evades chemotherapeutic damage even
      at high doses. An understanding of this population might be crucial for the
      success of bone marrow transplants for metastatic breast cancer and for the
      eradication of cancer cells in bone marrow. In vivo and in vitro studies have
      demonstrated gap junctional intercellular communication (GJIC) between bone
      marrow stroma and breast cancer cells. This review discusses GJIC in cancer
      metastasis, facilitating roles of mesenchymal stem cells (MSCs). In addition, the
      review addresses potential roles for miRNAs, including those already linked to
      cancer biology. The literature on MSCs is growing and their links to metastasis
      are beginning to be significant leads for the development of new drug targets for
      breast cancer. In summary, this review discusses interactions among GJIC, miRNAs
      and MSCs as future consideration for the development of cancer therapies.

PMID- 21886604
TI  - Genome-Wide Gene Expression Profiling of Nucleus Accumbens Neurons Projecting to
      Ventral Pallidum Using both Microarray and Transcriptome Sequencing.
AB  - The cellular heterogeneity of brain poses a particularly thorny issue in genome
      wide gene expression studies. Because laser capture microdissection (LCM) enables
      the precise extraction of a small area of tissue, we combined LCM with neuronal
      track tracing to collect nucleus accumbens shell neurons that project to ventral
      pallidum, which are of particular interest in the study of reward and addiction.
      Four independent biological samples of accumbens projection neurons were
      obtained. Approximately 500 pg of total RNA from each sample was then amplified
      linearly and subjected to Affymetrix microarray and Applied Biosystems sequencing
      by oligonucleotide ligation and detection (SOLiD) transcriptome sequencing (RNA
      seq). A total of 375 million 50-bp reads were obtained from RNA-seq.
      Approximately 57% of these reads were mapped to the rat reference genome (Baylor
      3.4/rn4). Approximately 11,000 unique RefSeq genes and 100,000 unique exons were
      identified from each sample. Of the unmapped reads, the quality scores were 4.74
      +/- 0.42 lower than the mapped reads. When RNA-seq and microarray data from the
      same samples were compared, Pearson correlations were between 0.764 and 0.798.
      The variances in data obtained for the four samples by microarray and RNA-seq
      were similar for medium to high abundance genes, but less among low abundance
      genes detected by microarray. Analysis of 34 genes by real-time polymerase chain
      reaction showed higher correlation with RNA-seq (0.66) than with microarray
      (0.46). Further analysis showed 20-30 million 50-bp reads are sufficient to
      provide estimates of gene expression levels comparable to those produced by
      microarray. In summary, this study showed that picogram quantities of total RNA
      obtained by LCM of ~700 individual neurons is sufficient to take advantage of the
      benefits provided by the transcriptome sequencing technology, such as low
      background noise, high dynamic range, and high precision.

PMID- 21886605
TI  - GSK-3 as a Target for Lithium-Induced Neuroprotection Against Excitotoxicity in
      Neuronal Cultures and Animal Models of Ischemic Stroke.
AB  - The mood stabilizer lithium inhibits glycogen synthase kinase-3 (GSK-3) directly
      or indirectly by enhancing serine phosphorylation of both alpha and beta
      isoforms. Lithium robustly protected primary brain neurons from glutamate-induced
      excitotoxicity; these actions were mimicked by other GSK-3 inhibitors or
      silencing/inhibiting GSK-3alpha and/or beta isoforms. Lithium rapidly activated
      Akt to enhance GSK-3 serine phosphorylation and to block glutamate-induced Akt
      inactivation. Lithium also up-regulated Bcl-2 and suppressed glutamate-induced
      p53 and Bax. Induction of brain-derived neurotrophic factor (BDNF) was required
      for lithium's neuroprotection to occur. BDNF promoter IV was activated by GSK-3
      inhibition using lithium or other drugs, or through gene silencing/inactivation
      of either isoform. Further, lithium's neuroprotective effects were associated
      with inhibition of NMDA receptor-mediated calcium influx and down-stream
      signaling. In rodent ischemic models, post-insult treatment with lithium
      decreased infarct volume, ameliorated neurological deficits, and improved
      functional recovery. Up-regulation of heat-shock protein 70 and Bcl-2 as well as
      down-regulation of p53 likely contributed to lithium's protective effects.
      Delayed treatment with lithium improved functional MRI responses, which was
      accompanied by enhanced angiogenesis. Two GSK-3-regulated pro-angiogenic factors,
      matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor were
      induced by lithium. Finally, lithium promoted migration of mesenchymal stem cells
      (MSCs) by up-regulation of MMP-9 through GSK-3beta inhibition. Notably,
      transplantation of lithium-primed MSCs into ischemic rats enhanced MSC migration
      to the injured brain regions and improved the neurological performance. Several
      other GSK-3 inhibitors have also been reported to be beneficial in rodent
      ischemic models. Together, GSK-3 inhibition is a rational strategy to combat
      ischemic stroke and other excitotoxicity-related brain disorders.

PMID- 21886606
TI  - Glycogen synthase kinase-3 in the etiology and treatment of mood disorders.
AB  - The mood disorders major depressive disorder and bipolar disorder are prevalent,
      are inadequately treated, and little is known about their etiologies. A better
      understanding of the causes of mood disorders would benefit from improved animal
      models of mood disorders, which now rely on behavioral measurements. This review
      considers the limitations in relating measures of rodent behaviors to mood
      disorders, and the evidence from behavioral assessments indicating that glycogen
      synthase kinase-3 (GSK3) dysregulation promotes mood disorders and is a potential
      target for treating mood disorders. The classical mood stabilizer lithium was
      identified by studying animal behaviors and later was discovered to be an
      inhibitor of GSK3. Several mood-relevant behavioral effects of lithium in rodents
      have been identified, and most have now been shown to be due to its inhibition of
      GSK3. An extensive variety of pharmacological and molecular approaches for
      manipulating GSK3 are discussed, the results of which strongly support the
      proposal that inhibition of GSK3 reduces both depression-like and manic-like
      behaviors. Studies in human postmortem brain and peripheral cells also have
      identified correlations between alterations in GSK3 and mood disorders. Evidence
      is reviewed that depression may be associated with impaired inhibitory control of
      GSK3, and mania by hyper-stimulation of GSK3. Taken together, these studies
      provide substantial support for the hypothesis that inhibition of GSK3 activity
      is therapeutic for mood disorders. Future research should identify the causes of
      dysregulated GSK3 in mood disorders and the actions of GSK3 that contribute to
      these diseases.

PMID- 21886607
TI  - Identification of a specific assembly of the g protein golf as a critical and
      regulated module of dopamine and adenosine-activated cAMP pathways in the
      striatum.
AB  - In the principal neurons of striatum (medium spiny neurons, MSNs), cAMP pathway
      is primarily activated through the stimulation of dopamine D1 and adenosine A(2A)
      receptors, these receptors being mainly expressed in striatonigral and
      striatopallidal MSNs, respectively. Since cAMP signaling pathway could be altered
      in various physiological and pathological circumstances, including drug addiction
      and Parkinson's disease, it is of crucial importance to identify the molecular
      components involved in the activation of this pathway. In MSNs, cAMP pathway
      activation is not dependent on the classical Gs GTP-binding protein but requires
      a specific G protein subunit heterotrimer containing Galphaolf/beta2/gamma7 in
      particular association with adenylyl cyclase type 5. This assembly forms an
      authentic functional signaling unit since loss of one of its members leads to
      defects of cAMP pathway activation in response to D1 or A(2A) receptor
      stimulation, inducing dramatic impairments of behavioral responses dependent on
      these receptors. Interestingly, D1 receptor (D1R)-dependent cAMP signaling is
      modulated by the neuronal levels of Galphaolf, indicating that Galphaolf
      represents the rate-limiting step in this signaling cascade and could constitute
      a critical element for regulation of D1R responses. In both Parkinsonian patients
      and several animal models of Parkinson's disease, the lesion of dopamine neurons
      produces a prolonged elevation of Galphaolf levels. This observation gives an
      explanation for the cAMP pathway hypersensitivity to D1R stimulation, occurring
      despite an unaltered D1R density. In conclusion, alterations in the highly
      specialized assembly of Galphaolf/beta2/gamma7 subunits can happen in
      pathological conditions, such as Parkinson's disease, and it could have important
      functional consequences in relation to changes in D1R signaling in the striatum.

PMID- 21886609
TI  - How does the Visual Cortex of the Blind Acquire Auditory Responsiveness?

PMID- 21886610
TI  - Emotion and time perception: effects of film-induced mood.
AB  - Previous research into emotion and time perception has been designed to study the
      time perception of emotional events themselves (e.g., facial expression). Our aim
      was to investigate the effect of emotions per se on the subsequent time judgment
      of a neutral, non-affective event. In the present study, the participants were
      presented with films inducing a specific mood and were subsequently given a
      temporal bisection task. More precisely, the participants were given two temporal
      bisection tasks, one before and the other after viewing the emotional film. Three
      emotional films were tested: one eliciting fear, another sadness, and a neutral
      control film. In addition, the direct mood experience was assessed using the
      Brief Mood Introspective Scale that was administered to the participants at the
      beginning and the end of the session. The results showed that the perception of
      time did not change after viewing either the neutral control films or the sad
      films although the participants reported being sadder and less aroused after than
      before watching the sad film clips. In contrast, the stimulus durations were
      judged longer after than before viewing the frightening films that were judged to
      increase the emotion of fear and arousal level. In combination with findings from
      previous studies, our data suggest that the selective lengthening effect after
      watching frightening films was mediated by an effect of arousal on the speed of
      the internal clock system.

PMID- 21886611
TI  - The SMAs: Neural Substrate of the Temporal Accumulator?

PMID- 21886608
TI  - Striatal Signaling in L-DOPA-Induced Dyskinesia: Common Mechanisms with Drug
      Abuse and Long Term Memory Involving D1 Dopamine Receptor Stimulation.
AB  - Parkinson's disease is a common neurodegenerative disorder caused by the
      degeneration of midbrain substantia nigra dopaminergic neurons that project to
      the striatum. Despite extensive investigation aimed at finding new therapeutic
      approaches, the dopamine precursor molecule, 3,4-dihydroxyphenyl-l-alanine (l
      DOPA), remains the most effective and commonly used treatment. However, chronic
      treatment and disease progression lead to changes in the brain's response to l
      DOPA, resulting in decreased therapeutic effect and the appearance of
      dyskinesias. l-DOPA-induced dyskinesia (LID) interferes significantly with normal
      motor activity and persists unless l-DOPA dosages are reduced to below
      therapeutic levels. Thus, controlling LID is one of the major challenges in
      Parkinson's disease therapy. LID is the result of intermittent stimulation of
      supersensitive D1 dopamine receptors located in the very severely denervated
      striatal neurons. Through increased coupling to Galpha(olf), resulting in greater
      stimulation of adenylyl-cyclase, D1 receptors phosphorylate DARPP-32, and other
      protein kinase A targets. Moreover, D1 receptor stimulation activates
      extracellular signal-regulated kinase and triggers a signaling pathway involving
      mammalian target for rapamycin and modifications of histones that results in
      changes in translation, chromatin modification, and gene transcription. In turn,
      sensitization of D1 receptor signaling causes a widespread increase in the
      metabolic response to D1 agonists and changes in the activity of basal ganglia
      neurons that correlate with the severity of LID. Importantly, different studies
      suggest that dyskinesias may share mechanisms with drug abuse and long term
      memory involving D1 receptor activation. Here we review evidence implicating D1
      receptor signaling in the genesis of LID, analyze mechanisms that may translate
      enhanced D1 signaling into dyskinetic movements, and discuss the possibility that
      the mechanisms underlying LID are not unique to the Parkinson's disease brain.

PMID- 21886612
TI  - Exploring the 4th dimension: hippocampus, time, and memory revisited.

PMID- 21886613
TI  - Neural representation of temporal duration: coherent findings obtained with the
      "lossy integration" model.

PMID- 21886614
TI  - A Data-Driven Investigation of Gray Matter-Function Correlations in Schizophrenia
      during a Working Memory Task.
AB  - The brain is a vastly interconnected organ and methods are needed to investigate
      its long range structure(S)-function(F) associations to better understand
      disorders such as schizophrenia that are hypothesized to be due to distributed
      disconnected brain regions. In previous work we introduced a methodology to
      reduce the whole brain S-F correlations to a histogram and here we reduce the
      correlations to brain clusters. The application of our approach to sMRI [gray
      matter (GM) concentration maps] and functional magnetic resonance imaging data
      (general linear model activation maps during Encode and Probe epochs of a working
      memory task) from patients with schizophrenia (SZ, n = 100) and healthy controls
      (HC, n = 100) presented the following results. In HC the whole brain correlation
      histograms for GM-Encode and GM-Probe overlap for Low and Medium loads and at
      High the histograms separate, but in SZ the histograms do not overlap for any of
      the load levels and Medium load shows the maximum difference. We computed GM-F
      differential correlation clusters using activation for Probe Medium, and they
      included regions in the left and right superior temporal gyri, anterior
      cingulate, cuneus, middle temporal gyrus, and the cerebellum. Inter-cluster GM
      Probe correlations for Medium load were positive in HC but negative in SZ. Within
      group inter-cluster GM-Encode and GM-Probe correlation comparisons show no
      differences in HC but in SZ differences are evident in the same clusters where HC
      vs. SZ differences occurred for Probe Medium, indicating that the S-F integrity
      during Probe is aberrant in SZ. Through a data-driven whole brain analysis
      approach we find novel brain clusters and show how the S-F differential
      correlation changes during Probe and Encode at three memory load levels.
      Structural and functional anomalies have been extensively reported in
      schizophrenia and here we provide evidences to suggest that evaluating S-F
      associations can provide important additional information.

PMID- 21886615
TI  - Widespread Brain Areas Engaged during a Classical Auditory Streaming Task
      Revealed by Intracranial EEG.
AB  - The auditory system must constantly decompose the complex mixture of sound
      arriving at the ear into perceptually independent streams constituting accurate
      representations of individual sources in the acoustic environment. How the brain
      accomplishes this task is not well understood. The present study combined a
      classic behavioral paradigm with direct cortical recordings from neurosurgical
      patients with epilepsy in order to further describe the neural correlates of
      auditory streaming. Participants listened to sequences of pure tones alternating
      in frequency and indicated whether they heard one or two "streams." The
      intracranial EEG was simultaneously recorded from sub-dural electrodes placed
      over temporal, frontal, and parietal cortex. Like healthy subjects, patients
      heard one stream when the frequency separation between tones was small and two
      when it was large. Robust evoked-potential correlates of frequency separation
      were observed over widespread brain areas. Waveform morphology was highly
      variable across individual electrode sites both within and across gross brain
      regions. Surprisingly, few evoked-potential correlates of perceptual organization
      were observed after controlling for physical stimulus differences. The results
      indicate that the cortical areas engaged during the streaming task are more
      complex and widespread than has been demonstrated by previous work, and that, by
      and-large, correlates of bistability during streaming are probably located on a
      spatial scale not assessed - or in a brain area not examined - by the present
      study.

PMID- 21886616
TI  - Value and prediction error in medial frontal cortex: integrating the single-unit
      and systems levels of analysis.
AB  - The role of the anterior cingulate cortex (ACC) in cognition has been extensively
      investigated with several techniques, including single-unit recordings in rodents
      and monkeys and EEG and fMRI in humans. This has generated a rich set of data and
      points of view. Important theoretical functions proposed for ACC are value
      estimation, error detection, error-likelihood estimation, conflict monitoring,
      and estimation of reward volatility. A unified view is lacking at this time,
      however. Here we propose that online value estimation could be the key function
      underlying these diverse data. This is instantiated in the reward value and
      prediction model (RVPM). The model contains units coding for the value of cues
      (stimuli or actions) and units coding for the differences between such values and
      the actual reward (prediction errors). We exposed the model to typical
      experimental paradigms from single-unit, EEG, and fMRI research to compare its
      overall behavior with the data from these studies. The model reproduced the ACC
      behavior of previous single-unit, EEG, and fMRI studies on reward processing,
      error processing, conflict monitoring, error-likelihood estimation, and
      volatility estimation, unifying the interpretations of the role performed by the
      ACC in some aspects of cognition.

PMID- 21886617
TI  - A learning-style theory for understanding autistic behaviors.
AB  - Understanding autism's ever-expanding array of behaviors, from sensation to
      cognition, is a major challenge. We posit that autistic and typically developing
      brains implement different algorithms that are better suited to learn, represent,
      and process different tasks; consequently, they develop different interests and
      behaviors. Computationally, a continuum of algorithms exists, from lookup table
      (LUT) learning, which aims to store experiences precisely, to interpolation (INT)
      learning, which focuses on extracting underlying statistical structure
      (regularities) from experiences. We hypothesize that autistic and typical brains,
      respectively, are biased toward LUT and INT learning, in low- and high
      dimensional feature spaces, possibly because of their narrow and broad tuning
      functions. The LUT style is good at learning relationships that are local,
      precise, rigid, and contain little regularity for generalization (e.g., the name
      number association in a phonebook). However, it is poor at learning relationships
      that are context dependent, noisy, flexible, and do contain regularities for
      generalization (e.g., associations between gaze direction and intention, language
      and meaning, sensory input and interpretation, motor-control signal and movement,
      and social situation and proper response). The LUT style poorly compresses
      information, resulting in inefficiency, sensory overload (overwhelm), restricted
      interests, and resistance to change. It also leads to poor prediction and
      anticipation, frequent surprises and over-reaction (hyper-sensitivity), impaired
      attentional selection and switching, concreteness, strong local focus, weak
      adaptation, and superior and inferior performances on simple and complex tasks.
      The spectrum nature of autism can be explained by different degrees of LUT
      learning among different individuals, and in different systems of the same
      individual. Our theory suggests that therapy should focus on training autistic
      LUT algorithm to learn regularities.

PMID- 21886618
TI  - Unmixing binocular signals.
AB  - Incompatible images presented to the two eyes lead to perceptual oscillations in
      which one image at a time is visible. Early models portrayed this binocular
      rivalry as involving reciprocal inhibition between monocular representations of
      images, occurring at an early visual stage prior to binocular mixing. However,
      psychophysical experiments found conditions where rivalry could also occur at a
      higher, more abstract level of representation. In those cases, the rivalry was
      between image representations dissociated from eye-of-origin information, rather
      than between monocular representations from the two eyes. Moreover,
      neurophysiological recordings found the strongest rivalry correlate in
      inferotemporal cortex, a high-level, predominantly binocular visual area involved
      in object recognition, rather than early visual structures. An unresolved issue
      is how can the separate identities of the two images be maintained after
      binocular mixing in order for rivalry to be possible at higher levels? Here we
      demonstrate that after the two images are mixed, they can be unmixed at any
      subsequent stage using a physiologically plausible non-linear signal-processing
      algorithm, non-negative matrix factorization, previously proposed for parsing
      object parts during object recognition. The possibility that unmixed left and
      right images can be regenerated at late stages within the visual system provides
      a mechanism for creating various binocular representations and interactions de
      novo in different cortical areas for different purposes, rather than inheriting
      then from early areas. This is a clear example how non-linear algorithms can lead
      to highly non-intuitive behavior in neural information processing.

PMID- 21886620
TI  - Cataract surgery in a patient with amyotrophic lateral sclerosis: a case report.
AB  - We report a cataract operation with complications in a patient with amyotrophic
      lateral sclerosis (ALS). The patient had a grade 4 mature brown cataract.
      Phacoemulsification with intraocular lens (IOL) implantation was planned;
      however, due to unexpected complications occurring during surgery, the operating
      technique was revised to an intracapsular cataract extraction. A very high
      vitreous pressure was found and therefore scleral fixating IOL was not implanted
      after anterior vitrectomy because of the possibility of choroidal effusion. The
      postoperative visual acuity improved sufficiently for the patient to communicate.
      Visual communication is of vital importance for an ALS patient and his
      caregivers. Therefore, surgery may be advisable in patients at a terminal stage
      with an advanced cataract, even if their general health condition may not seem
      appropriate for such an operation. Nevertheless, the intra- and postoperative
      course of the surgery may show unexpected complications and the surgeon should be
      prepared for such conditions.

PMID- 21886619
TI  - Exploiting Trial-to-Trial Variability in Multimodal Experiments.

PMID- 21886621
TI  - Neurosyphilis Masquerading as an Acute Adie's Tonic Pupil: Report of a Case.
AB  - We describe the case of a male patient who presented with anisocoria, and was
      initially diagnosed with an acute Adie's tonic pupil. On subsequent laboratory
      testing, he was found to have neurosyphilis. Magnetic resonance imaging
      demonstrated enhancement of the right oculomotor nerve. This case underscores the
      importance of considering this diagnosis in patients with acute onset internal
      ophthalmoplegia and hypersensitivity to dilute pilocarpine, even in the absence
      of other oculomotor nerve findings.

PMID- 21886622
TI  - Cardiac electromechanical models: from cell to organ.
AB  - The heart is a multiphysics and multiscale system that has driven the development
      of the most sophisticated mathematical models at the frontiers of computational
      physiology and medicine. This review focuses on electromechanical (EM) models of
      the heart from the molecular level of myofilaments to anatomical models of the
      organ. Because of the coupling in terms of function and emergent behaviors at
      each level of biological hierarchy, separation of behaviors at a given scale is
      difficult. Here, a separation is drawn at the cell level so that the first half
      addresses subcellular/single-cell models and the second half addresses organ
      models. At the subcellular level, myofilament models represent actin-myosin
      interaction and Ca-based activation. The discussion of specific models emphasizes
      the roles of cooperative mechanisms and sarcomere length dependence of
      contraction force, considered to be the cellular basis of the Frank-Starling law.
      A model of electrophysiology and Ca handling can be coupled to a myofilament
      model to produce an EM cell model, and representative examples are summarized to
      provide an overview of the progression of the field. The second half of the
      review covers organ-level models that require solution of the electrical
      component as a reaction-diffusion system and the mechanical component, in which
      active tension generated by the myocytes produces deformation of the organ as
      described by the equations of continuum mechanics. As outlined in the review,
      different organ-level models have chosen to use different ionic and myofilament
      models depending on the specific application; this choice has been largely
      dictated by compromises between model complexity and computational tractability.
      The review also addresses application areas of EM models such as cardiac
      resynchronization therapy and the role of mechano-electric coupling in
      arrhythmias and defibrillation.

PMID- 21886623
TI  - Aquaporin evolution in fishes.
AB  - Aquaporins represent a primordial group of transmembrane solvent channels that
      have been documented throughout the living biota. This facet alone emphasizes the
      positive selection pressure for proteins associated with intracellular fluid
      homeostasis. Amongst extant Eukaryota the highest gene copy number can be found
      in plants and teleosts, a feature that reflects the genomic duplication history
      in both groups. In this minireview we discuss the discovery, structure,
      duplication, and diversification of the aquaporin superfamily. We focus on
      teleosts as the main models, but include data available for other organisms to
      provide a broader perspective.

PMID- 21886624
TI  - Impaired Wheel Running Exercise in CLC-1 Chloride Channel-Deficient Myotonic
      Mice.
AB  - BACKGROUND: Genetic deficiency of the muscle CLC-1 chloride channel leads to
      myotonia, which is manifested most prominently by slowing of muscle relaxation.
      Humans experience this as muscle stiffness upon initiation of contraction,
      although this can be overcome with repeated efforts (the "warm-up" phenomenon).
      The extent to which CLC-1 deficiency impairs exercise activity is controversial.
      We hypothesized that skeletal muscle CLC-1 chloride channel deficiency leads to
      severe reductions in spontaneous exercise. METHODOLOGY/PRINCIPAL FINDINGS: To
      examine this quantitatively, myotonic CLC-1 deficient mice were provided access
      to running wheels, and their spontaneous running activity was quantified
      subsequently. Differences between myotonic and normal mice in running were not
      present soon after introduction to the running wheels, but were fully established
      during week 2. During the eighth week, myotonic mice were running significantly
      less than normal mice (322 +/- 177 vs 5058 +/- 1253 m/day, P = 0.025).
      Furthermore, there were considerable reductions in consecutive running times
      (18.8 +/- 1.5 vs 59.0 +/- 3.7 min, P < 0.001) and in the distance per consecutive
      running period (58 +/- 38 vs 601 +/- 174 m, P = 0.048) in myotonic compared with
      normal animals. CONCLUSION/SIGNIFICANCE: These findings indicate that CLC-1
      chloride deficient myotonia in mice markedly impairs spontaneous exercise
      activity, with reductions in both total distance and consecutive running times.

PMID- 21886625
TI  - Role of MicroRNAs in Insect Host-Microorganism Interactions.
AB  - MicroRNAs (miRNAs) have appeared as important regulators of various biological
      processes including development, cancer, immunity, and host-microorganism
      interactions. Accumulating evidence demonstrates the differential expression of
      host miRNAs upon infection by various microorganisms and the involvement of
      microorganism-encoded miRNAs in host manipulation. Some of these alterations
      could be part of a host response to an infection to limit replication and
      dissemination of the microorganism or, conversely, due to manipulation of the
      host miRNA pathway by the microorganism to facilitate its replication. Insights
      into the role of miRNAs in host defense responses and host manipulation by
      microorganisms will enable a better understanding of host-microorganism
      interactions.

PMID- 21886626
TI  - Social experience does not abolish cultural diversity in eye movements.
AB  - Adults from Eastern (e.g., China) and Western (e.g., USA) cultural groups display
      pronounced differences in a range of visual processing tasks. For example, the
      eye movement strategies used for information extraction during a variety of face
      processing tasks (e.g., identification and facial expressions of emotion
      categorization) differs across cultural groups. Currently, many of the
      differences reported in previous studies have asserted that culture itself is
      responsible for shaping the way we process visual information, yet this has never
      been directly investigated. In the current study, we assessed the relative
      contribution of genetic and cultural factors by testing face processing in a
      population of British Born Chinese adults using face recognition and expression
      classification tasks. Contrary to predictions made by the cultural differences
      framework, the majority of British Born Chinese adults deployed "Eastern" eye
      movement strategies, while approximately 25% of participants displayed "Western"
      strategies. Furthermore, the cultural eye movement strategies used by individuals
      were consistent across recognition and expression tasks. These findings suggest
      that "culture" alone cannot straightforwardly account for diversity in eye
      movement patterns. Instead a more complex understanding of how the environment
      and individual experiences can influence the mechanisms that govern visual
      processing is required.

PMID- 21886627
TI  - Modeling Single-Trial ERP Reveals Modulation of Bottom-Up Face Visual Processing
      by Top-Down Task Constraints (in Some Subjects).
AB  - We studied how task constraints modulate the relationship between single-trial
      event-related potentials (ERPs) and image noise. Thirteen subjects performed two
      interleaved tasks: on different blocks, they saw the same stimuli, but they
      discriminated either between two faces or between two colors. Stimuli were two
      pictures of red or green faces that contained from 10 to 80% of phase noise, with
      10% increments. Behavioral accuracy followed a noise dependent sigmoid in the
      identity task but was high and independent of noise level in the color task. EEG
      data recorded concurrently were analyzed using a single-trial ANCOVA: we assessed
      how changes in task constraints modulated ERP noise sensitivity while regressing
      out the main ERP differences due to identity, color, and task. Single-trial ERP
      sensitivity to image phase noise started at about 95-110 ms post-stimulus onset.
      Group analyses showed a significant reduction in noise sensitivity in the color
      task compared to the identity task from about 140 ms to 300 ms post-stimulus
      onset. However, statistical analyses in every subject revealed different results:
      significant task modulation occurred in 8/13 subjects, one showing an increase
      and seven showing a decrease in noise sensitivity in the color task. Onsets and
      durations of effects also differed between group and single-trial analyses: at
      any time point only a maximum of four subjects (31%) showed results consistent
      with group analyses. We provide detailed results for all 13 subjects, including a
      shift function analysis that revealed asymmetric task modulations of single-trial
      ERP distributions. We conclude that, during face processing, bottom-up
      sensitivity to phase noise can be modulated by top-down task constraints, in a
      broad window around the P2, at least in some subjects.

PMID- 21886628
TI  - Orthographic influences when processing spoken pseudowords: theoretical
      implications.
AB  - When we hear an utterance, is the orthographic representation of that utterance
      activated when it is being processed? Orthographic influences have been
      previously examined in relation to spoken pseudoword processing in three
      different paradigms. Unlike real word processing, no orthographic effects with
      pseudowords have been observed in a phoneme goodness ratings task, and there is a
      mixed outcome in studies looking for spelling-sound consistency effects. In
      contrast, the orthography of spoken pseudohomographs has been shown to be
      activated, given that they prime their homographic base word. Explanations are
      sought for the findings in these three paradigms, leading to an exploration of
      theoretical models of spoken word recognition.

PMID- 21886629
TI  - Native experience with a tone language enhances pitch discrimination and the
      timing of neural responses to pitch change.
AB  - Native tone language experience has been linked with alterations in the
      production and perception of pitch in language, as well as with the brain
      response to linguistic and non-linguistic tones. Here we use two experiments to
      address whether these changes apply to the discrimination of simple pitch changes
      and pitch intervals. Event related potentials (ERPs) were recorded from native
      Mandarin speakers and a control group during a same/different task with pairs of
      pure tones differing only in pitch height, and with pure tone pairs differing
      only in interval distance. Behaviorally, Mandarin speakers were more accurate
      than controls at detecting both pitch and interval changes, showing a sensitivity
      to small pitch changes and interval distances that was absent in the control
      group. Converging evidence from ERPs obtained during the same tasks revealed an
      earlier response to change relative to no-change trials in Mandarin speakers, as
      well as earlier differentiation of trials by change direction relative to
      controls. These findings illustrate the cross-domain influence of language
      experience on the perception of pitch, suggesting that the native use of tonal
      pitch contours in language leads to a general enhancement in the acuity of pitch
      representations.

PMID- 21886630
TI  - Younger but Not Older Adults Benefit from Salient Feedback during Learning.
AB  - Older adults are impaired in reinforcement learning (RL) when feedback is
      partially ambiguous (e.g., Eppinger and Kray, 2011). In this study we examined
      whether older adults benefit from salient feedback information during learning.
      We used an electrophysiological approach and investigated 15 younger and 15 older
      adults with a RL task in which they had to learn stimulus-response associations
      under two learning conditions. In the positive learning conditions, participants
      could gain 50 Cents for a correct response but did not gain or lose money (*00
      Cent) for an incorrect response. In negative learning conditions, they could lose
      50 Cents for an incorrect response but did not gain or lose money (*00 Cent) for
      a correct response. As the identical outcome "00 Cent" is either better or worse
      than the alternative outcome depending on the learning condition, this feedback
      type is ambiguous. To examine the influence of feedback salience we compared this
      condition with a condition in which positive and negative outcomes were color
      coded and thereby clearly separable. The behavioral results indicated that
      younger adults reached higher accuracy levels under salient feedback conditions.
      Moreover, the error-related negativity and the feedback-related negativity for
      losses were larger if the good-bad dimension of feedback was salient. Hence, in
      younger adults salient feedback facilitates the rapid evaluation of outcomes on a
      good-bad dimension and by this supports learning. In contrast, for older adults
      we obtained neither behavioral nor electrophysiological effects of feedback
      salience. The older adults' performance monitoring system therefore appears less
      flexible in integrating additional information in this evaluation process.

PMID- 21886631
TI  - Global properties of natural scenes shape local properties of human edge
      detectors.
AB  - Visual cortex analyzes images by first extracting relevant details (e.g., edges)
      via a large array of specialized detectors. The resulting edge map is then
      relayed to a processing pipeline, the final goal of which is to attribute meaning
      to the scene. As this process unfolds, does the global interpretation of the
      image affect how local feature detectors operate? We characterized the local
      properties of human edge detectors while we manipulated the extent to which the
      statistical properties of the surrounding image conformed to those encountered in
      natural vision. Although some aspects of local processing were unaffected by
      contextual manipulations, we observed significant alterations in the operating
      characteristics of the detector which were solely attributable to a higher-level
      semantic interpretation of the scene, unrelated to lower-level aspects of image
      statistics. Our results suggest that it may be inaccurate to regard early feature
      detectors as operating outside the domain of higher-level vision; although there
      is validity in this approach, a full understanding of their properties requires
      the inclusion of knowledge-based effects specific to the statistical regularities
      found in the natural environment.

PMID- 21886632
TI  - The Bodily Expressive Action Stimulus Test (BEAST). Construction and Validation
      of a Stimulus Basis for Measuring Perception of Whole Body Expression of
      Emotions.
AB  - Whole body expressions are among the main visual stimulus categories that are
      naturally associated with faces and the neuroscientific investigation of how body
      expressions are processed has entered the research agenda this last decade. Here
      we describe the stimulus set of whole body expressions termed bodily expressive
      action stimulus test (BEAST), and we provide validation data for use of these
      materials by the community of emotion researchers. The database was composed of
      254 whole body expressions from 46 actors expressing 4 emotions (anger, fear,
      happiness, and sadness). In all pictures the face of the actor was blurred and
      participants were asked to categorize the emotions expressed in the stimuli in a
      four alternative-forced-choice task. The results show that all emotions are well
      recognized, with sadness being the easiest, followed by fear, whereas happiness
      was the most difficult. The BEAST appears a valuable addition to currently
      available tools for assessing recognition of affective signals. It can be used in
      explicit recognition tasks as well as in matching tasks and in implicit tasks,
      combined either with facial expressions, with affective prosody, or presented
      with affective pictures as context in healthy subjects as well as in clinical
      populations.

PMID- 21886633
TI  - Attentional inhibition in bilingual naming performance: evidence from delta-plot
      analyses.
AB  - It has been argued that inhibition is a mechanism of attentional control in
      bilingual language performance. Evidence suggests that effects of inhibition are
      largest in the tail of a response time (RT) distribution in non-linguistic and
      monolingual performance domains. We examined this for bilingual performance by
      conducting delta-plot analyses of naming RTs. Dutch-English bilingual speakers
      named pictures using English while trying to ignore superimposed neutral Xs or
      Dutch distractor words that were semantically related, unrelated, or
      translations. The mean RTs revealed semantic, translation, and lexicality
      effects. The delta plots leveled off with increasing RT, more so when the mean
      distractor effect was smaller as compared with larger. This suggests that the
      influence of inhibition is largest toward the distribution tail, corresponding to
      what is observed in other performance domains. Moreover, the delta plots
      suggested that more inhibition was applied by high- than low-proficiency
      individuals in the unrelated than the other distractor conditions. These results
      support the view that inhibition is a domain-general mechanism that may be
      optionally engaged depending on the prevailing circumstances.

PMID- 21886634
TI  - Two words, one meaning: evidence of automatic co-activation of translation
      equivalents.
AB  - Research on the processing of translations offers important insights on how
      bilinguals negotiate the representation of words from two languages in one mind
      and one brain. Evidence so far has shown that translation equivalents effectively
      activate each other as well as their shared concept even when translations lack
      of any formal overlap (i.e., non-cognates) and even when one of them is presented
      subliminally, namely under masked priming conditions. In the lexical decision
      studies testing masked translation priming effects with unbalanced bilinguals a
      remarkably stable pattern emerges: larger effects in the dominant (L1) to the non
      dominant (L2) translation direction, than vice versa. Interestingly, this
      asymmetry vanishes when simultaneous and balanced bilinguals are tested,
      suggesting that the linguistic profile of the bilinguals could be determining the
      pattern of cross-language lexico-semantic activation across the L2 learning
      trajectory. The present study aims to detect whether L2 proficiency is the
      critical variable rendering the otherwise asymmetric cross-language activation of
      translations obtained in the lexical decision task into symmetric. Non-cognate
      masked translation priming effects were examined with three groups of Greek (L1)
      English (L2) unbalanced bilinguals, differing exclusively at their level of L2
      proficiency. Although increased L2 proficiency led to improved overall L2
      performance, masked translation priming effects were virtually identical across
      the three groups, yielding in all cases significant but asymmetric effects (i.e.,
      larger effects in the L1 -> L2 than in the L2 -> L1 translation direction). These
      findings show that proficiency does not modulate masked translation priming
      effects at intermediate levels, and that a native-like level of L2 proficiency is
      needed for symmetric effects to emerge. They furthermore, pose important
      constraints on the operation of the mechanisms underlying the development of
      cross-language lexico-semantic links.

PMID- 21886635
TI  - Negative emotion impairs conflict-driven executive control.
AB  - Cognition and emotion interact in important ways to shape ongoing behaviors. In
      this study, we investigated the interaction between conflict-driven executive
      control adjustments and emotion during a face-word Stroop-like paradigm. Neutral
      and negative images were employed to manipulate emotion. We were particularly
      interested in contrasting two hypotheses of the impact of emotion on conflict
      adaptation effects. On the one hand, resource accounts of cognitive-emotional
      interactions predict that behavioral adjustments following incongruent trials
      would be decreased when participants also have to process a negative stimulus. On
      the other hand, affect regulation models predict that negative emotion should
      increase behavioral adjustments. We found that task-irrelevant negative stimuli
      significantly reduced conflict-driven control effects (i.e., conflict adaptation)
      compared to neutral images. We interpret the findings in terms of shared
      resources between proactive control mechanisms and emotional processing. Our
      findings demonstrate that emotion interacts with executive mechanisms responsible
      for dynamic behavioral adjustments that are tied to environmental demands, a
      central facet of flexible, goal-directed behavior.

PMID- 21886636
TI  - Identification of new signaling components in the sensory epithelium of human
      saccule.
AB  - OBJECTIVE: To locate components and target proteins of relevance for the cAMP and
      cGMP signaling networks including cAMP and cGMP phosphodiesterases (PDEs), salt
      inducible kinases (SIKs), subunits of Na+, K+-ATPases, and aquaporins (AQPs) in
      the human saccule. METHODS: The human saccule was dissected out during the
      removal of vestibular schwannoma via the translabyrinthine approach and
      immediately fixed. Immunohistochemistry was performed using PDE, SIK, Na(+), K(+)
      ATPase, and AQP antibodies. RESULTS: PDEs selective for cAMP (PDE4A, PDE4D, and
      PDE8A) and cGMP (PDE9A) as well a dual specificity PDE (PDE10A) were detected in
      the sensory epithelium of the saccule. Furthermore, AQP2, 4, and 9, SIK1 and the
      alpha-1 subunit of the Na(+), K(+)-ATPase were detected. CONCLUSION: cAMP and
      cGMP are important regulators of ion and water homeostasis in the inner ear. The
      identification of PDEs and SIK1 in the vestibular system offers new treatment
      targets for endolymphatic hydrops. Exactly how the PDEs are connected to SIK1 and
      the SIK1 substrate Na(+), K(+)-ATPase and to AQPs 2, 4, 9 remains to be
      elucidated. The dissection of the signaling networks utilizing these components
      and evaluating their roles will add new basic knowledge regarding inner ear
      physiology.

PMID- 21886638
TI  - Iron limitation of a springtime bacterial and phytoplankton community in the ross
      sea: implications for vitamin b(12) nutrition.
AB  - The Ross Sea is home to some of the largest phytoplankton blooms in the Southern
      Ocean. Primary production in this system has previously been shown to be iron
      limited in the summer and periodically iron and vitamin B(12) colimited. In this
      study, we examined trace metal limitation of biological activity in the Ross Sea
      in the austral spring and considered possible implications for vitamin B(12)
      nutrition. Bottle incubation experiments demonstrated that iron limited
      phytoplankton growth in the austral spring while B(12), cobalt, and zinc did not.
      This is the first demonstration of iron limitation in a Phaeocystis antarctica
      dominated, early season Ross Sea phytoplankton community. The lack of B(12)
      limitation in this location is consistent with previous Ross Sea studies in the
      austral summer, wherein vitamin additions did not stimulate P. antarctica growth
      and B(12) was limiting only when bacterial abundance was low. Bottle incubation
      experiments and a bacterial regrowth experiment also revealed that iron addition
      directly enhanced bacterial growth. B(12) uptake measurements in natural water
      samples and in an iron fertilized bottle incubation demonstrated that bacteria
      serve not only as a source for vitamin B(12), but also as a significant sink, and
      that iron additions enhanced B(12) uptake rates in phytoplankton but not
      bacteria. Additionally, vitamin uptake rates did not become saturated upon the
      addition of up to 95 pM B(12). A rapid B(12) uptake rate was observed after 13
      min, which then decreased to a slower constant uptake rate over the next 52 h.
      Results from this study highlight the importance of iron availability in limiting
      early season Ross Sea phytoplankton growth and suggest that rates of vitamin
      B(12) production and consumption may be impacted by iron availability.

PMID- 21886637
TI  - Stepwise approach to myopathy in systemic disease.
AB  - Muscle diseases can constitute a large variety of both acquired and hereditary
      disorders. Myopathies in systemic disease results from several different disease
      processes including endocrine, inflammatory, paraneoplastic, infectious, drug-
      and toxin-induced, critical illness myopathy, metabolic, and myopathies with
      other systemic disorders. Patients with systemic myopathies often present acutely
      or sub acutely. On the other hand, familial myopathies or dystrophies generally
      present in a chronic fashion with exceptions of metabolic myopathies where
      symptoms on occasion can be precipitated acutely. Most of the inflammatory
      myopathies can have a chance association with malignant lesions; the incidence
      appears to be specifically increased only in patients with dermatomyositis. In
      dealing with myopathies associated with systemic illnesses, the focus will be on
      the acquired causes. Management is beyond the scope of this chapter. Prognosis is
      based upon the underlying cause and, most of the time, carries a good prognosis.
      In order to approach a patient with suspected myopathy from systemic disease, a
      stepwise approach is utilized.

PMID- 21886639
TI  - Fungal polysaccharides: biological activity beyond the usual structural
      properties.
AB  - Studies on structure and function of polysaccharides in biological systems
      classically involve sequence and compositional analyses, anomeric configuration,
      type of glycosidic linkage, and presence of substituents. Recent studies,
      however, indicates that other structural parameters, so far little explored, can
      directly influence the biological activity of microbial polysaccharides. Among
      these parameters, we highlight the molecular dimensions of Cryptococcus
      neoformans polysaccharides, which appear to be inversely correlated with their
      immunobiological activity. These recent observations raise new concepts about the
      structure and function of polysaccharides, which stimulates the design of new
      experimental approaches and suggests previously unknown applications.

PMID- 21886641
TI  - Spontaneous rupture of the spleen associated with Legionella pneumonia.
AB  - Spontaneous rupture of the spleen associated with Legionella pneumonia is a rare
      and life-threatening complication; only three cases have been reported to date.
      The authors describe a case of a 47-year-old man who presented with pneumonia and
      abdominal pain. He underwent a splenectomy, and was successfully treated with
      clarithromycin and levofloxacin.

PMID- 21886640
TI  - Bacterial Catabolism of Dimethylsulfoniopropionate (DMSP).
AB  - Dimethylsulfoniopropionate (DMSP) is a metabolite produced primarily by marine
      phytoplankton and is the main precursor to the climatically important gas
      dimethylsulfide (DMS). DMS is released upon bacterial catabolism of DMSP, but it
      is not the only possible fate of DMSP sulfur. An alternative
      demethylation/demethiolation pathway results in the eventual release of
      methanethiol, a highly reactive volatile sulfur compound that contributes little
      to the atmospheric sulfur flux. The activity of these pathways control the
      natural flux of sulfur released to the atmosphere. Although these biochemical
      pathways and the factors that regulate them are of great interest, they are
      poorly understood. Only recently have some of the genes and pathways responsible
      for DMSP catabolism been elucidated. Thus far, six different enzymes have been
      identified that catalyze the cleavage of DMSP, resulting in the release of DMS.
      In addition, five of these enzymes appear to produce acrylate, while one produces
      3-hydroxypropionate. In contrast, only one enzyme, designated DmdA, has been
      identified that catalyzes the demethylation reaction producing
      methylmercaptopropionate (MMPA). The metabolism of MMPA is performed by a series
      of three coenzyme-A mediated reactions catalyzed by DmdB, DmdC, and DmdD.
      Interestingly, CandidatusPelagibacter ubique, a member of the SAR11 clade of
      Alphaproteobacteria that is highly abundant in marine surface waters, possessed
      functional DmdA, DmdB, and DmdC enzymes. Microbially mediated transformations of
      both DMS and methanethiol are also possible, although many of the biochemical and
      molecular genetic details are still unknown. This review will focus on the recent
      discoveries in the biochemical pathways that mineralize and assimilate DMSP
      carbon and sulfur, as well as the areas for which a comprehensive understanding
      is still lacking.

PMID- 21886642
TI  - Successful treatment of uncomplicated gonococcal urethritis in HIV-infected
      patients with single-dose oral cefpodoxime.
AB  - Fluoroquinolones are no longer recommended for the treatment of gonococcal
      infections in the United States. Cephalosporins - ceftriaxone and cefixime - are
      the treatment of choice, as suggested by the Centers for Disease Control and
      Prevention (USA). There are limited data on the efficacy of cefpodoxime for the
      treatment of uncomplicated gonococcal infections. Two cases of HIV-infected
      homosexual men who were successfully treated with cefpodoxime for urethritis
      caused by Neisseria gonorrhoeae are described in the present study.

PMID- 21886643
TI  - The relationship among antibiotic consumption, socioeconomic factors and climatic
      conditions.
AB  - BACKGROUND: Antibiotic consumption in human populations is one of the factors
      responsible for the emergence of resistant organisms. It is important to track
      population-based data on an ongoing basis, and to explore the determinants of
      regional variation in antibiotic consumption. METHODS: Population-level data were
      obtained on all outpatient oral antibiotic prescriptions dispensed within British
      Columbia (BC) between 1996 and 2007. Prescriptions were expressed as the defined
      daily dose per 1000 inhabitants. Geographical information systems mapping was
      used to display the spatial variations of antibiotic consumption in BC. The
      relationships among antibiotic consumption, socioeconomic factors and climatic
      conditions were explored using Pearson's correlation and regression modelling.
      RESULTS: Overall antibiotic consumption was highest in the northern regions of
      BC. Higher rates of consumption were associated with a greater proportion of the
      Aboriginal population, lower levels of education and individuals younger than 15
      years of age. An inverse correlation was found between some classes of
      antibiotics and the following factors: individuals older than 65 years of age,
      mortality rate, doctor-to-population ratio, household size and higher July
      temperatures. The adjusted regression analyses indicated that higher antibiotic
      consumption was associated with a higher proportion of Aboriginals and household
      income. CONCLUSION: Different rates of antibiotic consumption exist within BC.
      The use of antibiotics is correlated with several socioeconomic factors and
      climatic conditions. It may be useful to consider these factors when designing
      policies to address antibiotic consumption in the community.

PMID- 21886644
TI  - A new publishing model for The Canadian Journal of Infectious Diseases & Medical
      Microbiology.

PMID- 21886645
TI  - A new publishing model for The Canadian Journal of Infectious Diseases & Medical
      Microbiology.

PMID- 21886646
TI  - The 'One Health' paradigm: Time for infectious diseases clinicians to take note?

PMID- 21886647
TI  - Invasive group A streptococcal disease: Management and chemoprophylaxis.
AB  - Given the potentially devastating consequences of severe invasive group A
      streptococcal disease, attention has been directed toward the role of
      chemoprophylaxis and the optimization of management strategies. In response to
      this issue, Canadian guidelines were previously developed. However, the uptake of
      these recommendations is variable across Canada. The present document summarizes
      key components of the recommendations for use by Canadian physicians. The
      importance of penicillin in the treatment of group A streptococcal disease is
      reaffirmed, and the role of clindamycin is discussed. In addition, in situations
      in which chemoprophylaxis may be considered, the preferred agents are summarized.

PMID- 21886648
TI  - Population-level interventions to reduce the development and transmission of
      community-associated antimicrobial resistance: A perspective from the National
      Collaborating Centre for Infectious Diseases.

PMID- 21886650
TI  - A review of alternative practices to antimicrobial use for disease control in the
      commercial feedlot - executive summary.

PMID- 21886649
TI  - Antimicrobial use and resistance in pigs and chickens: A review of the science,
      policy and control practices from farm to slaughter - executive summary.

PMID- 21886651
TI  - Strategies to control community-associated antimicrobial resistance among enteric
      bacteria and methicillin-resistant Staphylococcus aureus in Canada - executive
      summary.

PMID- 21886652
TI  - Ceftobiprole: First reported experience in osteomyelitis.
AB  - A 74-year-old man with long-standing diabetes presented with advanced infection
      of the right forefoot associated with septic arthritis and osteomyelitis
      involving the second and third metatarsophalangeal joints. Polymicrobial
      infection, which included methicillin-resistant Staphylococcus aureus, was
      documented. First-line antibiotic therapy, which included vancomycin, was not
      tolerated. A durable cure was obtained following a six-week course of intravenous
      ceftobiprole medocaril combined with local surgery. The present report is the
      first to administer intravenous ceftobiprole medocaril to a patient with
      methicillin-resistant S aureus-associated septic arthritis and osteomyelitis.

PMID- 21886653
TI  - Natural killer cell leukaemia.
AB  - A 42-year-old white woman, who was a general practitioner referral to the medical
      team, presented with a 3-day history of left upper quadrant pain; an urgent
      private ultrasound scan had showed splenomegaly. She was initially admitted with
      sepsis without an obvious cause but with a differential diagnosis of a
      haematological malignancy. Her admission blood tests showed a mildly reduced
      white cell count and low platelets. Her symptoms progressed and she developed
      right upper quadrant pain. Her blood counts deteriorated showing a disseminated
      intravascular coagulation (DIC) picture and mildly deranged liver function tests.
      Blood films were non-diagnostic. A CT scan of the abdomen/pelvis showed
      splenomegaly and also hepatomegaly and ascites, not seen in her initial
      ultrasound scan. Multiple cultures of blood/urine/ascites and infective serology
      were unremarkable.She was transferred to a larger tertiary centre under the care
      of the surgeons with presumed abdominal sepsis and underwent an open laparotomy,
      which showed a big firm liver and spleen but no obvious cause for sepsis. The
      infectious disease team were unable to find a cause, and haematology became
      involved to investigate the possibility of a haematological malignancy. The
      patient underwent two bone marrow biopsies, a percutaneous liver biopsy and had
      flow cytometry of her ascitic fluid, which revealed the diagnosis of a natural
      killer cell leukaemia. After some slight improvement on steroids, the patient was
      given cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab (CHOP-R)
      chemotherapy. The patient had an initial response to chemotherapy, with reduction
      in ascitic volume and hepatosplenomegaly, and normalisation of her coagulation.
      This was accompanied by an overall improvement in her physical condition. She had
      a second cycle of CHOP-R, but unfortunately approximately 2 weeks after that, she
      deteriorated rapidly. She was too weak for salvage chemotherapy, so she was put
      on comfort care. She died peacefully.

PMID- 21886654
TI  - Rare case of "red man" syndrome in a female patient treated with oral vancomycin
      for Clostridium difficile diarrhoea.
AB  - A 58-year-old Caucasian woman was admitted for knee replacement but during the
      postoperative period she developed sepsis due to pneumonia, which was treated
      with coamoxiclav and then piperacillin (for 2 weeks). She had renal failure,
      which needed haemofiltration. During her recovery she had diarrhoea due to
      Clostridium difficile, which was not controlled with metronidazole. Vancomycin
      was therefore given, but she developed urticarial erythematous skin rash and
      hence it was stopped. She was not on any other new medications and a vasculitic
      screen was negative. A dermatologist reviewed her file as well. The skin rash
      subsided after 2 weeks with topical emollients and chlorphenamine tablets. Her
      diarrhoea eventually settled and she went home well. Though classically described
      in men, this "red man" syndrome (features of urticarial erythematous rash due to
      oral vancomycin) has been previously reported in case reports and in literature
      reviews.

PMID- 21886655
TI  - Very late bare metal stent thrombosis with concomitant patent drug eluting stent
      in the same vessel: a case for a suggestive hypothesis.
AB  - We report a case of very late stent thrombosis of a bare metal stent with a
      concurrent drug eluting stent's patency in the same coronary vessel, in a patient
      undergoing primary angioplasty who discontinued his clopidogrel regimen a few
      weeks after successful deployment of the stents.

PMID- 21886656
TI  - Meconium-induced periorchitis.
AB  - A testicular tumour-like lesion or a solid extratesticular mass are serious
      postnatal problems with a broad spectrum of inflammatory or tumorous causes and
      possible differential diagnoses. In this case report, an extraordinary case of a
      newborn boy with a rare cause of a periorchitis is described.A premature boy
      infant (25-year-old mother with obesity) was diagnosed as having a disturbance of
      prosperity. A plain film of the abdomen showed a dilated intestine (no
      pathological findings in abdominal ultrasound, in particular, no ascites). After
      3 postnatal months of clinical observation at the hospital including temporary
      parenteral nutrition, hydrocele at both sides was diagnosed. Therefore, the boy
      underwent surgical exploration. Intraoperatively, the processus vaginalis
      peritonei was surprisingly filled with meconium; because of that, the situs was
      extensively rinsed. In addition, the boy underwent an operation for the right and
      left hydrocele. The testes were preserved (on follow-up investigation there were
      no further problems).Pathohistological investigation confirmed meconium
      periorchitis, which is a rare postnatal disease and which can only develop in
      cases of former meconium peritonitis and if the processus vaginalis peritonei is
      open. The precise details of cause and pathophysiology in this case may
      significantly help in avoiding unnecessary orchiectomy.

PMID- 21886657
TI  - Improvement in sleep apnoea associated with switch from simvastatin to
      pravastatin.
AB  - Sleep problems have been reported as an adverse effect of statins. In a
      randomised trial, simvastatin at 20 mg produced significantly worse sleep quality
      than either placebo or pravastatin 40 mg. A possible relation to sleep apnoea was
      hypothesised. Here, the case of a 67-year-old man who experienced sleep apnoea on
      simvastatin 20 mg is presented. Objective nightly testing showed a prompt,
      marked, sustained and statistically significant improvement in the obstructive
      apnoea index when the patient switched to pravastatin 20 mg.

PMID- 21886658
TI  - A case report of pulmonary alveolar proteinosis.
AB  - This is a case of pulmonary alveolar proteinosis that presented in an inner city
      hospital in Birmingham, UK. The patient was a previously well 42-year-old man,
      who went on to experience unusual cerebral complications of the disease. The
      presentation, imaging findings and diagnostic histology findings are described.
      Pulmonary alveolar proteinosis is a rare but important diagnosis. Characteristic
      high-resolution CT findings include diffuse ground glass density with
      superimposed interlobular septal thickening, which is described as the "crazy
      paving" pattern. Diagnosis is made by bronchoalveolar lavage. Pathologically the
      disease is characterised by alveolar filling with a lipid rich, proteinaceous
      material (positive to periodic acid-Schiff stain) while the lung interstitium
      remains relatively normal. Morbidity and mortality can be improved by treatment
      with whole lung lavage.

PMID- 21886659
TI  - Cerebral venous sinus thrombosis presenting in pregnancy and puerperium.
AB  - Cerebral venous sinus thrombosis (CVST) during pregnancy and puerperium is an
      uncommon diagnosis. CVST can present with wide range of symptoms and signs, and
      most of the time it is left undiagnosed. Here, three cases of CVST in early
      pregnancy and puerperium in young women who presented with seizure attacks,
      altered sensorium and severe headache, respectively, are reported. Subsequent
      imaging with MRI and magnetic resonance venography (MRV) showed CVST in the first
      two cases, whereas in the third case it showed a venous infarction. All were
      treated with low molecular weight heparin followed by warfarin. They all made
      excellent recoveries and are in regular follow-up.

PMID- 21886660
TI  - Liver abscess within the first week of life in a very low birthweight infant.
AB  - Liver abscess is rare in neonates. The present report concerns a preterm neonate
      with history of antenatal laser ablation therapy (to prevent twin to twin
      transfusion syndrome), who developed liver abscesses within a few days of life.
      Conservative treatment with antibiotics led to the normalisation of inflammatory
      markers, leaving an echogenic (calcified) area in the liver.

PMID- 21886661
TI  - A ventricular thrombus mimicking a tumour.
AB  - Primary cardiac tumours are a rare occurrence in clinical practice. Mural or
      pedunculated thrombi are other infrequent findings. These are usually associated
      with underlying heart disease, present in the left atrium or occupying aneurysms
      in the ventricular wall, usually the apex. The case of a 33-year-old woman with a
      pedunculated cardiac mass not having these latter characteristics is reported.
      She had experienced dyspnoea and lower extremity oedema for 3 years on referral.
      Echocardiography revealed a mass emerging from the interventricular septum, and a
      myxoma was suspected. Heart surgery was performed and the findings were a
      thrombus and large extent of septal and apical mural fibrosis. An
      endoaneurysmorraphy was performed with exclusion of fibrotic walls from the
      ventricular cavity.

PMID- 21886662
TI  - Onset and recovery of hepatic and renal injury after deliberate acute paracetamol
      overdose.
AB  - A 54-year-old woman presented to hospital after deliberate acute ingestion of
      paracetamol 20 g. Despite early administration of a standardised acetylcysteine
      regimen, the patient developed acute liver impairment and acute renal impairment.
      Prolonged acetylcysteine administration and supportive measures allowed
      restoration of normal liver and renal function. Early presentation to hospital
      and prolonged duration of follow-up gave an unusual opportunity to examine the
      onset and duration of paracetamol-induced hepatic and renal impairment.

PMID- 21886663
TI  - Intraparenchymal haematoma related to true middle meningeal artery aneurysm: a
      case report.
AB  - Non-traumatic middle meningeal artery aneurysm and rupture resulting in
      intracranial haemorrhage is rare. In the present case, a 73-year-old man was
      admitted to hospital with a history of a minor head trauma. A CT scan of the head
      revealed a 2*2 cm intraparenchymal haematoma without significant mass effect in
      the left temporal lobe. The cerebral angiogram revealed a middle meningeal artery
      aneurysm. Intracerebral haematoma due to extracranial aneurysm is extremely rare,
      but should be considered when the history is suspicious and cranial CT is non
      contributory.

PMID- 21886664
TI  - A case of severe visceral leishmaniasis resulting from travel to Greece.
AB  - Visceral leishmaniasis is rare in the developed world, particularly in
      immunocompetent hosts. It must be considered, however, in patients who are
      unwell, febrile and unresponsive to conventional antibiotics with a history of
      travel to areas where leishmaniasis is endemic. A case of more severe clinical
      manifestations than have been previously reported in Australia is presented here.
      The recent introduction of PCR technology for the detection of Leishmania in
      Australia has improved the diagnosis and management of leishmaniasis. Treatment
      with liposomal amphotericin B proved to be very effective in this severe case of
      visceral leishmaniasis.

PMID- 21886665
TI  - The morphological and molecular diagnosis of lung cancer.
AB  - BACKGROUND: In Germany, lung cancer causes more deaths than any other malignant
      disease. Its main etiology is smoking, but other risk factors need to be
      considered as well. The morphological, molecular and biological phenotype is
      complex and should no longer be just categorized as either small-cell or non
      small cell lung cancer. METHODS: This review article is based on the authors'
      longstanding involvement in the scientific investigation and diagnostic
      evaluation of lung cancer, including contributions to the current WHO
      classification and collaboration in the new interdisciplinary classification of
      adenocarcinoma. The relevant literature was selectively reviewed. RESULTS: Lung
      cancer is morphologically classified into four main subtypes-small-cell
      carcinoma, squamous-cell carcinoma, adenocarcinoma, and large-cell carcinoma.
      Genetic and molecular analyses have revealed distinct differences within
      subtypes; in particular, adenocarcinomas can be further subdivided. Complex
      techniques of genomic analysis are now available, but clinicopathological data
      are still the most important determinants of prognosis and are clearly better for
      this purpose than molecular classification alone. Nonetheless, the assessment of
      specific molecular markers is becoming increasingly important. CONCLUSION: The
      morphological and molecular classification of lung cancer is undergoing a re
      evaluation which will lead to more accurate assessment of individual prognoses
      and to improved prediction of the response to specific treatment regimens.

PMID- 21886668
TI  - Paradoxical reaction in ADHD.

PMID- 21886666
TI  - Hemoglobinopathies: clinical manifestations, diagnosis, and treatment.
AB  - BACKGROUND: Hemoglobinopathies are among the most common inherited diseases
      around the world. They have become much more common recently in northern and
      central Europe, including Germany, due to immigration. METHOD: Selective review
      of the literature with consideration of national guidelines. RESULTS: The
      hemoglobinopathies encompass all genetic diseases of hemoglobin. They fall into
      two main groups: thalassemia syndromes and structural hemoglobin variants
      (abnormal hemoglobins). alpha- and beta-thalassemia are the main types of
      thalassemia; the main structural hemoglobin variants are HbS, HbE and HbC. There
      are many subtypes and combined types in each group. The highly variable clinical
      manifestations of the hemoglobinopathies range from mild hypochromic anemia to
      moderate hematological disease to severe, lifelong, transfusion-dependent anemia
      with multiorgan involvement. Stem-cell transplantation is the preferred treatment
      for the severe forms of thalassemia. Supportive, rather than curative, treatment
      consists of periodic blood transfusions for life, combined with iron chelation.
      Drugs to treat the symptoms of sickle-cell disease include analgesics,
      antibiotics, ACE inhibitors and hydroxyurea. Blood transfusions should be given
      only when strictly indicated. More than 90% of patients currently survive into
      adulthood. Optimally treated patients have a projected life span of 50 to 60
      years. CONCLUSION: Hemoglobinopathies are a public health issue in today's
      multiethnic German population. Adequate care of the affected patients requires a
      wide variety of diagnostic and therapeutic measures.

PMID- 21886669
TI  - Cognitive neurodynamics in china.

PMID- 21886670
TI  - Visual pattern recognition based on spatio-temporal patterns of retinal ganglion
      cells' activities.
AB  - Neural information is processed based on integrated activities of relevant
      neurons. Concerted population activity is one of the important ways for retinal
      ganglion cells to efficiently organize and process visual information. In the
      present study, the spike activities of bullfrog retinal ganglion cells in
      response to three different visual patterns (checker-board, vertical gratings and
      horizontal gratings) were recorded using multi-electrode arrays. A measurement of
      subsequence distribution discrepancy (MSDD) was applied to identify the spatio
      temporal patterns of retinal ganglion cells' activities in response to different
      stimulation patterns. The results show that the population activity patterns were
      different in response to different stimulation patterns, such difference in
      activity pattern was consistently detectable even when visual adaptation occurred
      during repeated experimental trials. Therefore, the stimulus pattern can be
      reliably discriminated according to the spatio-temporal pattern of the neuronal
      activities calculated using the MSDD algorithm.

PMID- 21886671
TI  - Visual saliency: a biologically plausible contourlet-like frequency domain
      approach.
AB  - In this paper we propose a fast frequency domain saliency detection method that
      is also biologically plausible, referred to as frequency domain divisive
      normalization (FDN). We show that the initial feature extraction stage, common to
      all spatial domain approaches, can be simplified to a Fourier transform with a
      contourlet-like grouping of coefficients, and saliency detection can be achieved
      in frequency domain. Specifically, we show that divisive normalization, a model
      of cortical surround inhibition, can be conducted in frequency domain. Since
      Fourier coefficients are global in space, we extend to this model by conducting
      piecewise FDN (PFDN) using overlapping local patches to provide better biological
      plausibility. Not only do FDN and PFDN outperform current state-of-the-art
      methods in eye fixation prediction, they are also faster. Speed and simplicity
      are advantages of our frequency domain approach, and its biological plausibility
      is the main contribution of our paper.

PMID- 21886672
TI  - Using interspike intervals to quantify noise effects on spike trains in
      temperature encoding neurons.
AB  - This paper examines how noise interacts with the non-linear dynamical mechanisms
      of neuronal stimulus. We study the spike trains generated by a minimal Hodgkin
      Huxley type model of a cold receptor neuron. The distributions of interspike
      intervals(ISIs) of purely deterministic simulations exhibit considerable
      differences compared to the noisy ones. We quantify the effect of noise using ISI
      return plots and the ISI-distance recently proposed by Kreuz et al. (J Neurosci
      Meth, 165:151-161, 2007). It is shown that the spike trains of a cold receptor
      neuron are more strongly affected by noise for low temperatures than for high
      temperatures. This trend is also observed in both regimes of cold receptors:
      tonic firing(which occurs for low and high temperatures) and bursting (which
      occurs for intermediate temperatures).

PMID- 21886673
TI  - A semi-supervised support vector machine approach for parameter setting in motor
      imagery-based brain computer interfaces.
AB  - Parameter setting plays an important role for improving the performance of a
      brain computer interface (BCI). Currently, parameters (e.g. channels and
      frequency band) are often manually selected. It is time-consuming and not easy to
      obtain an optimal combination of parameters for a BCI. In this paper, motor
      imagery-based BCIs are considered, in which channels and frequency band are key
      parameters. First, a semi-supervised support vector machine algorithm is proposed
      for automatically selecting a set of channels with given frequency band. Next,
      this algorithm is extended for joint channel-frequency selection. In this
      approach, both training data with labels and test data without labels are used
      for training a classifier. Hence it can be used in small training data case.
      Finally, our algorithms are applied to a BCI competition data set. Our data
      analysis results show that these algorithms are effective for selection of
      frequency band and channels when the training data set is small.

PMID- 21886674
TI  - Model based generalization analysis of common spatial pattern in brain computer
      interfaces.
AB  - In the motor imagery based Brain Computer Interface (BCI) research, Common
      Spatial Pattern (CSP) algorithm is used widely as a spatial filter on multi
      channel electroencephalogram (EEG) recordings. Recently the overfitting effect of
      CSP has been gradually noticed, but what influence the overfitting is still
      unclear. In this work, the generalization of CSP is investigated by a simple
      linear mixing model. Several factors in this model are discussed, and the
      simulation results indicate that channel numbers and the correlation between
      signals influence the generalization of CSP significantly. A larger number of
      training trials and a longer time length of the trial would prevent overfitting.
      The experiments on real data also verify our conclusion.

PMID- 21886675
TI  - Analyzing inner and outer synchronization between two coupled discrete-time
      networks with time delays.
AB  - This paper studies two kinds of synchronization between two discrete-time
      networks with time delays, including inner synchronization within each network
      and outer synchronization between two networks. Based on Lyapunov stability
      theory and linear matrix inequality (LMI), sufficient conditions for two discrete
      time networks to be asymptotic stability are derived in terms of LMI. Finally
      numerical examples are given to illustrate the effectiveness of our derived
      results. The theoretical understanding provides insights into the dynamics of two
      or more neural networks with appropriate couplings.

PMID- 21886676
TI  - Feature extraction and recognition of epileptiform activity in EEG by combining
      PCA with ApEn.
AB  - This paper proposes a new method for feature extraction and recognition of
      epileptiform activity in EEG signals. The method improves feature extraction
      speed of epileptiform activity without reducing recognition rate. Firstly,
      Principal component analysis (PCA) is applied to the original EEG for dimension
      reduction and to the decorrelation of epileptic EEG and normal EEG. Then discrete
      wavelet transform (DWT) combined with approximate entropy (ApEn) is performed on
      epileptic EEG and normal EEG, respectively. At last, Neyman-Pearson criteria are
      applied to classify epileptic EEG and normal ones. The main procedure is that the
      principle component of EEG after PCA is decomposed into several sub-band signals
      using DWT, and ApEn algorithm is applied to the sub-band signals at different
      wavelet scales. Distinct difference is found between the ApEn values of epileptic
      and normal EEG. The method allows recognition of epileptiform activities and
      discriminates them from the normal EEG. The algorithm performs well at
      epileptiform activity recognition in the clinic EEG data and offers a flexible
      tool that is intended to be generalized to the simultaneous recognition of many
      waveforms in EEG.

PMID- 21886677
TI  - Approximate expressions of the bifurcating periodic solutions in a neuron model
      with delay-dependent parameters by perturbation approach.
AB  - This paper is interested in gaining insights of approximate expressions of the
      bifurcating periodic solutions in a neuron model. This model shares the property
      of involving delay-dependent parameters. The presence of such dependence requires
      the use of suitable criteria which usually makes the analytical work so harder.
      Most existing methods for studying the nonlinear dynamics fail when applied to
      such a class of delay models. Although Xu et al. (Phys Lett A 354:126-136, 2006)
      studied stability switches, Hopf bifurcation and chaos of the neuron model with
      delay-dependent parameters, the dynamics of this model are still largely
      undetermined. In this paper, a detailed analysis on approximation to the
      bifurcating periodic solutions is given by means of the perturbation approach.
      Moreover, some examples are provided for comparing approximations with numerical
      solutions of the bifurcating periodic solutions. It shows that the dynamics of
      the neuron model with delay-dependent parameters is quite different from that of
      systems with delay-independent parameters only.

PMID- 21886678
TI  - Unconditional global exponential stability in Lagrange sense of genetic
      regulatory networks with SUM regulatory logic.
AB  - In this paper, the global exponential stability in Lagrange sense for genetic
      regulatory networks (GRNs) with SUM regulatory logic is firstly studied. By
      constructing appropriate Lyapunov-like functions, several criteria are presented
      for the boundedness, ultimate boundedness and global exponential attractivity of
      GRNs. It can be obtained that GRNs with SUM regulatory logic are unconditionally
      globally exponentially stable in Lagrange sense. These results can be applied to
      analyze monostable as well as multistable networks. Furthermore, to analyze the
      stability for GRNs more comprehensively, the existence of equilibrium point of
      GRNs is proved, and some sufficient conditions of the global exponential
      stability in Lyapunov sense for GRNs are derived. Finally two numerical examples
      are given to illustrate the application of the obtained results.

PMID- 21886679
TI  - Synthetic biology gains momentum in Europe.

PMID- 21886680
TI  - Synthetic biology of minimal living cells: primitive cell models and semi
      synthetic cells.
AB  - This article summarizes a contribution presented at the ESF 2009 Synthetic
      Biology focused on the concept of the minimal requirement for life and on the
      issue of constructive (synthetic) approaches in biological research. The attempts
      to define minimal life within the framework of autopoietic theory are firstly
      described, and a short report on the development of autopoietic chemical systems
      based on fatty acid vesicles, which are relevant as primitive cell models is
      given. These studies can be used as a starting point for the construction of more
      complex systems, firstly being inspired by possible origins of life scenarioes
      (and therefore by considering primitive functions), then by considering an
      approach based on modern biomacromolecular-encoded functions. At this aim, semi
      synthetic minimal cells are defined as those man-made vesicle-based systems that
      are composed of the minimal number of genes, proteins, biomolecules and which can
      be defined as living. Recent achievements on minimal sized semi-synthetic cells
      are then discussed, and the kind of information obtained is recognized as being
      distinctively derived by a constructive approach. Synthetic biology is therefore
      a fundamental tool for gaining basic knowledge about biosystems, and it should
      not be confined at all to the engineering side.

PMID- 21886681
TI  - A computational study of liposome logic: towards cellular computing from the
      bottom up.
AB  - In this paper we propose a new bottom-up approach to cellular computing, in which
      computational chemical processes are encapsulated within liposomes. This
      "liposome logic" approach (also called vesicle computing) makes use of supra
      molecular chemistry constructs, e.g. protocells, chells, etc. as minimal cellular
      platforms to which logical functionality can be added. Modeling and simulations
      feature prominently in "top-down" synthetic biology, particularly in the
      specification, design and implementation of logic circuits through bacterial
      genome reengineering. The second contribution in this paper is the demonstration
      of a novel set of tools for the specification, modelling and analysis of "bottom
      up" liposome logic. In particular, simulation and modelling techniques are used
      to analyse some example liposome logic designs, ranging from relatively simple
      NOT gates and NAND gates to SR-Latches, D Flip-Flops all the way to 3 bit ripple
      counters. The approach we propose consists of specifying, by means of P systems,
      gene regulatory network-like systems operating inside proto-membranes. This P
      systems specification can be automatically translated and executed through a
      multiscaled pipeline composed of dissipative particle dynamics (DPD) simulator
      and Gillespie's stochastic simulation algorithm (SSA). Finally, model selection
      and analysis can be performed through a model checking phase. This is the first
      paper we are aware of that brings to bear formal specifications, DPD, SSA and
      model checking to the problem of modeling target computational functionality in
      protocells. Potential chemical routes for the laboratory implementation of these
      simulations are also discussed thus for the first time suggesting a potentially
      realistic physiochemical implementation for membrane computing from the bottom
      up.

PMID- 21886682
TI  - Variable production windows for porcine trypsinogen employing synthetic inducible
      promoter variants in Pichia pastoris.
AB  - Natural tools for recombinant protein production show technological limitations.
      Available natural promoters for gene expression in Pichia pastoris are either
      constitutive, weak or require the use of undesirable substances or procedures for
      induction. Here we show the application of deletion variants based on the well
      known methanol inducible AOX1 promoter and small synthetic promoters, where cis
      acting elements were fused to core promoter fragments. They enable differently
      regulated target protein expression and at the same time to replace methanol
      induction by a glucose or glycerol feeding strategy. Trypsinogen, the precursor
      of the serine protease trypsin, was expressed using these different promoters.
      Depending on the applied promoter the production window (i.e. the time of
      increasing product concentration) changed significantly. In fedbatch processes
      trypsinogen yields before induction with methanol were up to 10 times higher if
      variants of the AOX1 promoter were applied. In addition, the starting point of
      autoproteolytic product degradation can be predetermined by the promoter choice.

PMID- 21886683
TI  - Thermobifida fusca exoglucanase Cel6B is incompatible with the cellulosomal mode
      in contrast to endoglucanase Cel6A.
AB  - Cellulosomes are efficient cellulose-degradation systems produced by selected
      anaerobic bacteria. This multi-enzyme complex is assembled from a group of
      cellulases attached to a protein scaffold termed scaffoldin, mediated by a high
      affinity protein-protein interaction between the enzyme-borne dockerin module and
      the cohesin module of the scaffoldin. The enzymatic complex is attached as a
      whole to the cellulosic substrate via a cellulose-binding module (CBM) on the
      scaffoldin subunit. In previous works, we have employed a synthetic biology
      approach to convert several of the free cellulases of the aerobic bacterium,
      Thermobifida fusca, into the cellulosomal mode by replacing each of the enzymes'
      CBM with a dockerin. Here we show that although family six enzymes are not a part
      of any known cellulosomal system, the two family six enzymes of the T. fusca
      system (endoglucanase Cel6A and exoglucanase Cel6B) can be converted to work as
      cellulosomal enzymes. Indeed, the chimaeric dockerin-containing family six
      endoglucanase worked well as a cellulosomal enzyme, and proved to be more
      efficient than the parent enzyme when present in designer cellulosomes. In stark
      contrast, the chimaeric family six exoglucanase was markedly less efficient than
      the wild-type enzyme when mixed with other T. fusca cellulases, thus indicating
      its incompatibility with the cellulosomal mode of action.

PMID- 21886684
TI  - Trends in the Use of Evidence-based Therapies Early in the Course of Acute
      Myocardial Infarction and its Influence on Short Term Patient Outcomes.
AB  - AIM: To evaluate changes in management practices and its influence on short term
      hospital outcomes in patients with acute myocardial infarction (AMI) admitted
      during two different time periods, 2007 and 2004. METHODS AND RESULTS: We studied
      AMI patients from two acute coronary syndrome registries carried out in Kuwait in
      2007 and 2004. We included 1872 and 1197 patients from the 2007 and 2004
      registries, respectively. When compared with 2004, patients from the 2007
      registry had similar baseline clinical characteristics. In 2007 compared to 2004,
      during the in-hospital period, patients with AMI received significantly more
      statins (94% vs. 73%%, p<0.0001), Angiotensin converting enzyme (ACE) inhibitors
      and angiotensin receptor blockers (ARB) (70% vs. 47%, p<0.001), and Clopidogrel
      (38% vs. 4%, p<0.001), while beta-blockers use dropped in 2007 compared to 2004
      (63% vs. 68%, p=0.0066). The rates of in-hospital mortality and recurrent
      ischemia were significantly lower in the 2007 cohort compared with the 2004
      cohort (for mortality 2.2% vs. 3.9%, P=0.0008, for recurrent ischemia 13.7% vs.
      20.4%, P=0<0.0001).Higher utilization of angiotensin converting enzyme
      inhibitors, angiotensin receptor blockers and statins were the main contributors
      to the improved in-hospital mortality and morbidity. IN CONCLUSION: In the acute
      management of AMI, there was a significant increase in the use of statins, ACE
      inhibitors and Clopidogrel in 2007 compared to 2004. This was associated with a
      significant decrease in the in-hospital mortality and recurrent ischemia.
      Adherence to guidelines recommended therapies improved in-hospital outcomes.

PMID- 21886685
TI  - The influence in airforce soldiers through wearing certain types of army-issue
      footwear on muscle activity in the lower extremities.
AB  - The objective of the study was to analyse the influence of the shape and material
      of the military footwear worn by soldiers on muscle activity in the lower
      extremities, and whether such footwear could explain specific strain complaints
      and traumatic lesions in the region of the lower extremities.37 soldiers (one
      woman, 36 men) aged between 20 and 53 years underwent a dynamic electromyography
      (EMG) analysis. Wearing - one pair at a time - five different types of shoes, the
      subjects were asked to walk on a treadmill, where an EMG of the following muscles
      was taken: M. tibialis anterior, M. gastrocnemius mediales, M. gastrocnemius
      laterales, M. peroneus longus and M. rectus femoris.When the subjects wore old
      fashioned outdoor jogging shoes increased muscle activity was observed in the
      region of the M. peroneus longus. This can be interpreted as a sign of the upper
      ankle joint requiring increased support and thus explain the higher
      susceptibility to sprains experienced in connection with these shoes. When the
      subjects wore combat boots, increased activity was observed in the region of the
      Mm. tibialis anterior and rectus femoris. The specific activity differences that
      were observed in particular muscles may have influence in the occurrence of
      certain disorders, especially in untrained recruits. This can be linked to
      various strain-related disorders such as shin splints and patellofemoral pain.
      The data obtained using EMG can provide information about the likelihood of a
      clustering of the complaints experienced by soldiers during training or active
      service.

PMID- 21886687
TI  - Simultaneous Bilateral Flexion-Type Salter-Harris II Fractures of the Proximal
      Tibia: A Case Report and Review of the Literature.
AB  - A rare case is reported of bilateral physeal lesions of the proximal tibia
      classified as Salter-Harris type II, which occurred simultaneously after a
      "flexion type" injury in a 14-year-old boy. Treatment was conservative on the
      nondisplaced side and surgical, by closed reduction and internal fixation, on the
      displaced side. There was no previous diagnosis of Osgood-Schlatter disease.
      After reviewing all the cases described previously, which occurred either
      consecutively or simultaneously, we conclude that less resistance of the growth
      plate, typical of late adolescence, likely represents the cause of this type of
      lesion.

PMID- 21886686
TI  - Pre-operative status and quality of life following total joint replacement in a
      developing country: a prospective pilot study.
AB  - BACKGROUND: An increasing number of medical relief organizations have launched
      programs to perform total joint replacements in the developing world. There is a
      paucity of data on the clinical outcomes of these procedures. We documented pre-
      and post-operative pain and functional status in a group of low income Dominicans
      who underwent total hip or knee replacement performed by an American relief
      organization. METHODS: In March 2009 and 2010, we surveyed patients participating
      in Operation Walk Boston, a medical relief organization that provides total joint
      replacements to patients in the Dominican Republic. Questionnaires included the
      Western Ontario and McMaster University Osteoarthritis (WOMAC) Index scales and
      the Short-Form 36 (SF-36) scales for physical activity and mental health. Scores
      were transformed to a 0 - 100 point scale (100 is best). RESULTS: 81 individuals
      (mean age 61 years, 60% female) completed the pre-operative questionnaires.
      Twenty eight of the 35 who completed preoperative forms in 2009 also completed
      follow up forms in 2010 (follow-up rate 80%). Patients reported poor pre
      operative WOMAC function (mean = 33.6, sd = 22.0) and WOMAC pain (mean = 38.4, sd
      = 22.9) scores preoperatively. Mean post-operative WOMAC pain and function scores
      were 86.4 (sd = 13.1) and 88.1 (sd = 11.4) respectively. Improvement in pain and
      function was similar for patients undergoing hip (n=11) and knee (n=17)
      replacements. CONCLUSION: Total joint replacement was effective in relieving pain
      and restoring function in this program. These results are useful for comparison
      to outcomes in developed countries and for establishing benchmarks for future
      programs.

PMID- 21886688
TI  - Tissue engineering in orthopaedics and musculoskeletal sciences.

PMID- 21886689
TI  - Sources of adult mesenchymal stem cells applicable for musculoskeletal
      applications - a systematic review of the literature.
AB  - Mesenchymal stem cells (MSCs) were first discovered by Friedenstein and his
      colleagues in 1976 from bone marrow. The unique property of these cells was their
      potential to develop into fibroblastic colony forming cells. Since Friedenstein's
      discovery of these cells the interest in adult MSCs has been progressively
      growing. Nowadays MSCs are defined as undeveloped biological cells capable of
      proliferation, self renewal and regenerating tissues. All these properties of
      MSCs have been discovered in the past 35 years. MSCs can play a crucial role in
      tissue engineering, organogenesis, gene therapy, transplants as well as tissue
      injuries. These cells were mainly extracted from bone marrow but there have been
      additional sources for MSCs discovered in the laboratories including: muscle,
      dermis, trabecular bone, adipose tissue, periosteum, pericyte, blood, synovial
      membrane and so forth. The discovery of the alternative sources of MSCs helps
      widen the application of these cells in different areas of medicine. By way of
      illustration, they can be used in various therapeutic purposes such as tissue
      regeneration and repair in musculoskeletal diseases including osteonecrosis of
      femoral head, stimulating growth in children with osteogenesis imperfecta, disc
      regeneration, osteoarthritis and duchenne muscular dystrophy. In order to fully
      comprehend the characteristics and potential of MSCs future studies in this field
      are essential.

PMID- 21886690
TI  - The use of scaffolds in musculoskeletal tissue engineering.
AB  - The use of bioengineering scaffolds remains an integral part of the tissue
      engineering concept. A significant amount of basic science and clinical research
      has been focused on the regeneration of musculoskeletal tissues including bone,
      articular cartilage, meniscus, ligament and tendon. This review aims to provide
      the reader with a summary of the principals of using material scaffolds in
      musculoskeletal tissue engineering applications and how these materials may
      eventually come to be incorporated in clinical practice.

PMID- 21886691
TI  - The role of bioreactors in tissue engineering for musculoskeletal applications.
AB  - Tissue engineering involves using the principles of biology, chemistry and
      engineering to design a 'neotissue' that augments a malfunctioning in vivo
      tissue. The main requirements for functional engineered tissue include reparative
      cellular components that proliferate on a biocompatible scaffold grown within a
      bioreactor that provides specific biochemical and physical signals to regulate
      cell differentiation and tissue assembly. We discuss the role of bioreactors in
      tissue engineering and evaluate the principles of bioreactor design. We evaluate
      the methods of cell stimulation and review the bioreactors in common use today.

PMID- 21886692
TI  - The use of growth factors and mesenchymal stem cells in orthopaedics.
AB  - Stem cell therapy is an exciting and upcoming branch of tissue engineering with
      application in the field of orthopaedics. The most commonly used type of stem
      cells, mesenchymal stem cells (MSCs), can be easily isolated from bone marrow or
      synovium and cultured in vitro. Newer techniques using tissue engineering to
      regenerate musculoskeletal tissue by using biomimetic materials are now being
      studied. These osteoconductive three dimensional constructs seeded with MSCs are
      highly porous, biodegradable and biomechanically stable scaffolds which do not
      evoke an immunogenic host cell response. Research has shown the importance of
      growth factors in guiding and modulating the differentiation of MSCs in order to
      obtain the required cell type. Gene-based delivery systems have aided the
      delivery of sustained quantities of these growth factors. The evidence from
      growth factor enhanced tissue engineering studies for tissue healing looks very
      positive. This is a multi-disciplinary approach that integrates molecular,
      biochemical and clinical techniques with developmental and engineering processes.
      Initial studies indicate an immense potential for cell based strategies to
      enhance current orthopaedic approaches in skeletal tissue reconstruction.
      Ultimately, there is a need for randomised controlled trials on human populations
      to apply these findings to a clinical setting. Nevertheless, stem cell based
      tissue engineering in orthopaedics shows a promising future.

PMID- 21886693
TI  - Tissue Engineering Stem Cells - An e-Governance Strategy.
AB  - The rules of governance are changing. They are necessarily becoming more
      stringent as interventions offered to treat conditions carry unpredictable side
      effects, often associated with novel therapeutic vectors. The clinical relevance
      of this relates to the obligations of those involved in research, to ensure the
      best protection for subjects whilst encouraging the development of the field.
      Existing evidence supports the concept of e-Governance both in operational health
      research and more broadly in the strategic domain of policy formation. Building
      on the impact of the UK Comprehensive Research Network and recent EU Directives,
      it is now possible to focus on the issues of regulation for cell therapies in
      musculoskeletal science through the development of the Advanced Therapeutic
      Medicinal Products (ATMP) category of research products. This article reviews the
      framework that has borne this and the need for more detailed Virtual Research
      Integration and Collaboration (VRIC) systems to ensure regulatory compliance.
      Technology research and development plans must develop in close association
      between tissue engineering and treating clinicians. The scope of this strategy
      relates to the handling of human tissues the transport and storage of specimens
      in accordance with current EU directives and the Human Tissue Authority (HTA)
      regulations.

PMID- 21886694
TI  - Dupuytren's Disease: Review of the Current Literature.
AB  - Dupuytren's disease is one of the most common condition seen by hand surgeons. It
      is not only prevalent but can also be a most debilitating condition resulting in
      significant loss of function of the fingers involved. The cause of this disease,
      however still remains largely unknown although some recent evidence suggests a
      stem cell etiology. This review article summarizes the current known knowledge of
      Dupuytren's as well as the clinical findings, investigations and treatments
      available.

PMID- 21886695
TI  - Tissue engineering for bone production- stem cells, gene therapy and scaffolds.
AB  - A bone graft has been the gold standard treatment for repairing bone defects.
      However, due to bone grafts associated donor site morbidity several alternative
      bone substitutes options have been made available but with their added expense
      and limited osteoinductive properties they are not ideal. Therefore, research has
      begun in tissue engineering to investigate stem cells, which are one of the
      body's own mechanisms used to repair bone. Stem cells are clonogenic
      undifferentiated cells capable of self-renewal. Readily available from numerous
      of sources stem cells have the potential to differentiate in osteoblasts and
      chrondrocytes showing capability to repair both bone and cartilage. The known
      immunologic properties of stem cells further enhance their therapeutic appeal.
      Stem cells have shown to be excellent carriers for gene transfer having the
      capability to be transduced. Gene transfer could enable growth factors and bone
      morphogentic proteins to enhance bone repair. Stem cells are implanted onto
      scaffolds, which are structures capable of supporting tissue formation by
      allowing cell migration, proliferation and differentiation. Research aims to
      produce scaffolds that deliver and retain cells, allow for cell attachment has
      adequate biodegradability, biocompatibility and non-immunogenicity. However,
      having tried and testing numerous materials including synthetic and natural
      products research into the perfect scaffold product continues. This review aims
      to explain how stem cells were discovered, the techniques used to isolate stem
      cells, identify and manipulate them down different cell lineages and discuss the
      research into using stem cells to reconstruct bone using genetic modification and
      scaffolds.

PMID- 21886696
TI  - Mesenchymal stem cells and articular cartilage repair: clinical studies and
      future direction.
AB  - Cartilage is frequently injured but shows little capacity for repair. Current
      treatment options include the use of procedures that stimulate repair through the
      stimulation of subchondral bone marrow and result in the formation of
      fibrocartilage. There is considerable interest in the use of cell-based treatment
      strategies and there are limited studies describing the use of mesenchymal stem
      cells for cartilage repair with promising early results. This paper reviews the
      current treatment strategies for articular cartilage, describes use of
      mesenchymal stem cells for articular cartilage repair along with the results of
      clinical studies, and describes the future direction that these strategies are
      likely to take.

PMID- 21886697
TI  - Slow-growing melanoma: Report of five cases.
AB  - BACKGROUND: Epidemiologic data on melanoma reveal a considerable increase in
      incidence, especially of the early forms (melanoma in situ and early invasive
      melanoma), but the mortality rates are relatively stable. These data suggest the
      hypothesis of the existence of a melanoma with less aggressive biological
      behaviour. This hypothesis is, however, hard to be proven if the assumption is
      true that more and less aggressive melanomas very often exhibit overlapping
      clinical and histopathologic features. Digital dermoscopic imaging techniques
      permit today a detailed documentation of lesions over time and, therefore,
      represent an optimal tool to disclose the natural evolution of a given lesion. We
      present five case of slow-growing melanomas observed during a long-term period of
      follow-up. MAIN OBSERVATION: Five pigmented skin lesions from five patients with
      multiple atypical melanocytic nevi were examined at the baseline consultation and
      digital pictures were taken for monitoring purposes. The lesions have been
      followed-up for a long time because of the absence of significant changes over
      time. After a variable period of follow-up (1 to 10 years) all lesions were
      finally removed and subsequent histopathologic examination revealed early stage
      melanoma in all cases. CONCLUSION: Dermoscopy and digital follow up might be the
      key factors to improve the knowledge about the natural evolution of nevi and
      melanoma and the spectrum of undefined melanocytic proliferations.

PMID- 21886699
TI  - Rotundiform morphology during the first episode of pityriasis versicolor - a
      retrospective case-control study on a distinct clinical presentation.
AB  - We report a retrospective case-control study to investigate whether the
      rotundiform variant of pityriasis versicolor (PV) is significantly associated
      with the first episodes of PV. Our setting was a dermatology clinic run by a
      consultant dermatologist. We retrieved medical records of all patients with PV
      between April 1, 2002 and March 31, 2005. We identified patients with lesions
      forming closed round circles. We excluded patients with uncertain diagnosis or
      diagnosis not substantiated by Wood's light examination or skin scrapings for
      potassium hydroxide examination. For each patient, we retrieved the medical
      record of the next patient of the same sex and similar age (+/- three years) with
      documented non-rotundiform PV and diagnosis substantiated by investigations as
      the control subject.80 patients were diagnosed as having PV during the record
      retrieval period. 18 had clinical descriptions or clinical photographs
      documenting rotundiform PV. Five were excluded owing to uncertain diagnosis,
      unclear clinical descriptions, or diagnoses unsubstantiated by examination under
      Wood's light or skin scrapings for potassium hydroxide examination. 13 had
      definite diagnosis of rotundiform PV. Ten agreed to attend clinic. The response
      rate was 76.9%. Ten age-and-sex pair-matched control subjects with non
      rotundiform PV were recruited. Nine patients with rotundiform PV and two controls
      with non-rotundiform PV had their episode of PV representing their first episode
      of PV (p = 0.01; OR = 36.0, 95% CI: 2.2 - 866.9). We conclude that rotundiform PV
      is significantly associated with the first episode of PV. This phenomenon might
      be analogous to the herald patch being the primary lesion in pityriasis rosea.

PMID- 21886700
TI  - Milia-like idiopathic calcinosis cutis in an adult without Down's syndrome.
AB  - BACKGROUND: Milia-like idiopathic calcinosis cutis is a rare entity. Only 19
      cases have been reported so far, the majority of them developed in children with
      Down's syndrome. The mean age of the patients is 10.3 years, with a sex ratio of
      nine girls to ten boys. Hands are most commonly affected. MAIN OBSERVATION: We
      report a case of a 69-year-old, otherwise healthy woman, who developed milia-like
      idiopathic calcinosis cutis on her forehead. CONCLUSION: To our knowledge, we
      report the seventh case occurring in a patient without Down's syndrome, and the
      first case occurring in an elderly person.

PMID- 21886698
TI  - Cylindroma transforming into basal cell carcinoma in a patient with Brooke
      Spiegler syndrome.
AB  - BACKGROUND: Brooke-Spiegler syndrome is a rare condition with a predisposition to
      develop cutaneous adnexal neoplasms, especially cylindromas, trichoepitheliomas
      and spiradenomas. Malignant transformation of cylindromas is rare. In such cases
      usually cylindrocarcinomas develop within these lesions. We present an unusual
      case of basal cell carcinoma developing within a preexisting cylindroma. MAIN
      OBSERVATIONS: 58-year-old woman with a 30-year history of multiple dermal
      cylindromas extensively involving her scalp was referred for dermatological
      treatment. The patient reported that one of the long-lasting lesions, 5.5 cm in
      size, ulcerated within the foregoing few weeks. Histopathology confirmed
      cylindromas and basal cell carcinoma within the ulcerating tumor. Surgical
      excision of largest cylindroma tumors led to cosmetic and functional improvement.
      Magnetic resonance and computed tomography showed tumor infiltration into the
      skull lamina externa. Metastases were excluded by chest radiography and abdominal
      ultrasound examination. CONCLUSION: Patients with Brooke-Spiegler syndrome should
      be followed-up for malignant transformation of skin tumors to prevent deep
      penetration and possible metastases.

PMID- 21886701
TI  - Response of ocular pemphigus vulgaris to therapy. Case report and review of
      literature.
AB  - BACKGROUND: Pemphigus vulgaris is an autoimmune bullous disease characterized by
      blistering and erosions within skin and mucous membranes. Lesions appear most
      commonly on mucosal surfaces of the oral cavity. Ocular involvement in patients
      with PV has rarely been reported. MAIN OBSERVATION: A 47-year-old male patient
      with a 2 month history of oral erosions and dysphagia developed severe
      conjunctivitis with periodical presence of purulent discharge, photophobia and
      burning sensations. The diagnosis of pemphigus vulgaris was confirmed by
      histopathology, direct immunofluorescence and detection of anti-desmogelin 3
      antibodies in patients' serum. Treatment was introduced with prednisone at a dose
      of 80 mg per day (1 mg/kg) and cyclophosphamide at a dose of 100 mg daily (1.25
      mg/kg). After 7 days of therapy a significant reduction of eye symptoms was
      observed and after 4 weeks of treatment full clinical remission was achieved.
      CONCLUSIONS: The grounds for rare involvement of conjunctiva in pemphigus
      vulgaris is unclear. We hypothesize that inactivation of conjunctival desmoglein
      3 may be compensated by other desmosomal proteins. Severe conjunctivitis may be
      the dominating clinical manifestation in pemphigus vulgaris. This implies a need
      of establishing distinct severity criteria and therapeutic standards for ocular
      pemphigus. In our patient rapid clinical response was achieved after introducing
      combined treatment with prednisone and oral cyclophosphamide.

PMID- 21886702
TI  - Rituximab therapy of recalcitrant bullous dermatoses.
AB  - BACKGROUND: Rituximab is a monoclonal antibody directed against CD20 cell surface
      antigen of B-lymphocytes. Recent studies have demonstrated effectivity in
      recalcitrant bullous pemphigoid. The data available on other types of autoimmune
      bullous disease is more scant. MAIN OBSERVATION: Here we report on the successful
      adjuvant use of rituximab in mucous membrane pemphigoid and pemphigus vulgaris in
      two patients with the most refractory course of disease. Both patients achieved a
      good clinical response. CONCLUSIONS: Rituximab is a third line treatment of
      patients with pemphigus vulgaris and mucous membrane pemphigoid. In contrast to
      bullous pemphigoid, other bullous diseases do not always respond to a monotherapy
      with this monoclonal antibody. Nevertheless, biological therapy seems to work
      faster than established treatment in such cases. Risks and benefits of the
      treatment are discussed.

PMID- 21886703
TI  - Palmoplantar lichen planus: A rare presentation of a common disease.
AB  - BACKGROUND: Lichen planus (LP) is a chronic inflammatory skin disease commonly
      seen by dermatologists. MAIN OBSERVATION: The current case describes palmoplantar
      lichen planus, a rare variant of this disease that can easily be misdiagnosed.
      This case describes a patient that presented with multiple papules on his hands
      and plantar feet that had previously been diagnosed as tinea manum and psoriasis.
      A biopsy from the patient, however, was diagnostic of lichen planus. The patient
      was subsequently treated successfully with topical clobetasol propionate 0.05%
      ointment applied twice daily. CONCLUSIONS: Palmoplantar lichen planus is a rare
      disease that can be easily misdiagnosed. This case report emphasizes the role of
      the biopsy when presented with such patients.

PMID- 21886704
TI  - Giant pilomatricoma (pilomatrixoma) following an intramuscular injection.
AB  - We describe a young Indian male patient who developed a large solitary tumor
      following an intramuscular injection at the same location. The tumor was
      histologically proven to be a pilomatricoma. It was treated by surgical excision
      and there was no recurrence until one year after the operation. An alarming
      phenomenon following intramuscular injection is presented here for its novelty.

PMID- 21886706
TI  - Pilomatrixoma of the eyelid.
AB  - BACKGROUND: Pilomatrixoma is a benign tumor of the hair follicle that can
      transform into a malignant lesion, the pilomatrix carcinoma. We present an
      unusual case of an eyelid pilomatrixoma. MAIN OBSERVATION: A 37-year-old white
      male presented with rapidly growing, pedunculated lesion located at the superior
      right eyelid of five months duration. The lesion was excised under local
      anaesthesia. The sample was fixed in 10% formalin and histopathological as well
      as immunohistochemical analyses were performed. Results of both examinations were
      consistent with a benign pilomatrixoma. CONCLUSIONS: Even though the lesion had
      malignant clinical appearance, histopathology confirmed the diagnosis of a benign
      pilomatrixoma, supporting the decision not to make a more extensive surgery.

PMID- 21886705
TI  - Trichoscopy in genetic hair shaft abnormalities.
AB  - BACKGROUND: Diagnosis of hair shaft abnormalities is based on light microscopic
      examination of more than 50 plucked hairs. The aim of this study was to verify
      whether hair shaft abnormalities may be visualized by trichoscopy (hair and scalp
      videodermoscopy) and to analyze trichoscopic features of common genetic hair
      shaft dysplasias. METHOD: Patients with known genetic hair shaft disorders were
      included into the study. Trichoscopy was performed with the use of Fotofinder II
      videodermoscope. Images performed at 20-fold and 70-fold magnification were
      analysed. In selected cases 160-fold magnification was used for better
      visualization of hair shafts. RESULTS: Our results show that characteristic light
      microscopy features of Netherton syndrome, monilethrix, woolly hair syndrome,
      pili torti, pili annulati and trichothiodystrophy may be visualized by
      trichoscopy. CONCLUSION: Genetic hair shaft abnormalities may be diagnosed by
      trichoscopy in a single diagnostic session without the need of plucking or
      cutting them for diagnostic purposes.

PMID- 21886707
TI  - Multiple glomus tumors.
AB  - BACKGROUND: Solitary and multiple glomus tumors are vascular tumors arising from
      glomus cells. These two forms have distinct clinical and histopathological
      features, suggesting that they might have a different pathogenesis. The multiple
      form is less frequent than the solitary form. Its diagnosis and treatment are
      more problematic and often delayed. MAIN OBSERVATION: We present the case of a 40
      year-old patient, with a 20-year history of numerous non-tender disseminated blue
      papules. At the age of 30 years one of the lesions was excised and than regrew
      and became painful. The histological exam of the lesions was consistent with
      glomangioma, also known as glomus tumor. We performed surgical resection of the
      nodular and painful lesions. CONCLUSION: The diagnosis of glomus tumor is easily
      suspected when the lesion is painful located in the subungual region. However, if
      the lesions are multiple and extradigitally located, the clinical diagnosis may
      be difficult and requires having in mind this differential diagnosis. Our case
      also shows that glomus tumors may regrow after excision in the same location.

PMID- 21886708
TI  - Isolated plexiform schwannoma of the hand.
AB  - BACKGROUND: The plexiform schwannoma, a peripheral nerve sheath tumor, is a very
      rare entity. But dermatologists should be familiar with since they may be the
      first who make diagnosis possible by taking a deep biopsy. MAIN OBSERVATION: A 24
      year-old male presented with multiple asymptomatic subcutaneous nodules of the
      palmar side of his right hand. Histologic investigations revealed a plexiform
      schwannoma with numerous Antoni-A areas. There was no evidence of
      neurofibromatosis type 1 or 2. CONCLUSIONS: Plexiform schwannoma of the hand is a
      rare nerve sheath tumor. In individual (symptomatic) cases hand surgery is an
      option that needs a critical indication. In every case histologic investigations
      are mandatory to confirm the diagnosis and not to overlook the malignant variant
      of this disease.

PMID- 21886709
TI  - Primary cutaneous CD30+ anaplastic large cell lymphoma: report of a rare case.
AB  - Primary cutaneous anaplastic large cell lymphoma (PCALCL) is a rare type of non
      Hodgkin's lymphoma comprising approximately 0.9-9.0% of all cutaneous lymphomas.
      PCALCL is characterized by the absence of systemic involvement, spontaneous
      regression and low recurrence rate especially in localized lesions.We present a
      47-year-old female with a 11/2-year history of two asymptomatic erythematous
      indurated plaques on the right arm. Skin punch biopsy revealed dense infiltrates
      of non-epidermotropic, large, irregularly-shaped lymphocytes with hyperchromatic
      and pyknotic nuclei. Immunohistochemistry revealed that these atypical cells are
      anaplastic lymphoma kinase (ALK) positive, CD30+, CD3-, CD20- and epithelial
      membrane antigen (EMA) negative. Clinical, histopathological and
      immunohistochemical findings are consistent with PCALCL. Work-ups revealed no
      systemic involvement. Short course CHOP (Cyclophosphamide, Doxorubicin,
      Vincristine, and Prednisone) chemotherapy resulted in total resolution of skin
      lesions; however, recurrence was noted 12 months after treatment. She then
      underwent radiotherapy and achieved complete remission.Because the clinical
      presentation of PCALCL can be variable, a high index of suspicion is necessary in
      patients presenting with chronic plaques and nodules unresponsive to topical or
      oral medications.

PMID- 21886710
TI  - Bilateral extensive linear nodules on upper extremities in a child - a rare
      presentation of neurofibromatosis type 1 (Recklinghausen disease).
AB  - BACKGROUND: Type 1 neurofibromatosis is a common neurocutaneous disease
      characterised by cafe-au-lait macules, neurofibromas, plexiform neurofibromas,
      axillary freckling, optic glioma, and Lisch nodules. MAIN OBSERVATIONS: We report
      a 10-year-old boy with a rare presentation of type 1 neurofibromatosis,
      presenting with bilateral, multiple linear asymptomatic nodules extending from
      the axillae to the wrists, bilateral thickening of ulnar and supraorbital nerves,
      and 16 cafe cafe-au-lait macules over 0.5 cm in diameter on trunk and
      extremities, and bilateral axillary freckles. We diagnosed neurofibromatosis 1
      clinically on the basis of NIH diagnostic criteria. CONCLUSION: As the clinical
      criteria were fulfilled, we believe that excisional biopsy as an invasive
      procedure was not clinically indicated for a 10-year-old child in this scenario.
      The patient has to be followed-up for possible malignant transformation of
      tumors.

PMID- 21886711
TI  - An unusual case of DRESS syndrome.
AB  - BACKGROUND: DRESS syndrome (drug reaction with eosinophilia and systemic
      symptoms) is a rare but severe drug reaction. OBSERVATIONS: A 27-year-old male
      with paranoid schizophrenia was hospitalized with all three diagnostic criteria
      of DRESS syndrome: cutaneous drug eruption, hematological abnormalities (presence
      of atypical lymphocytes on blood smear) and systemic involvement (generalized
      lymphadenopathy and hepatitis). On hospitalization the patient exhibited an
      unusual fever pattern of high temperatures in the morning hours and lower
      temperatures towards evening. In this case of a patient who needs life-long
      therapy, we demonstrated the value of the IFN-gamma release test, which showed
      positive reactivity to 3 out of 9 suspicious drugs: paracetamol, phenytoin and
      dypirone, allowing for more therapeutic options. After therapy, at 6-month follow
      up the patient is doing well under haloperidol treatment, laboratory values
      including liver function tests are normal and his skin condition is good.
      CONCLUSION: We suggest that clinicians take the fever pattern of high
      temperatures in the morning hours and lower temperatures towards evening into
      account in a patient presenting with a severe cutaneous drug eruption. An
      interferone-gamma release test may facilitate identification of drugs responsible
      for the drug reaction.

PMID- 21886712
TI  - Dermoscopy of pigmented oral lesions.
AB  - Dermoscopy is a noninvasive diagnostic technique that permits the visualization
      of morphologic features that are not visible to the naked eye. It is currently
      widely used for examination of pigmented skin lesions and early detection of
      cutaneous melanoma. Dermoscopy of mucous membranes is significantly less
      investigated and less popular among clinicians.This article reviews current
      knowledge about characteristic dermoscopy features of pigmented lesions of the
      oral mucous membranes and lips. It has to emphasized that a major advantage of
      dermoscopy is the capability to exclude melanoma and avoid unnecessary excisional
      biopsies and extensive surgery, often resulting in significant disfigurement of
      face and oral cavity.It has to be pointed out that there is a necessity to
      intensify research, which would result in clear-cut dermoscopy criteria for
      mucosal melanoma and the need for constructing thin, flexible dermoscopes
      suitable for investigation of oral mucous membranes.

PMID- 21886713
TI  - Fixed drug eruption followed by lichen aureus during abatacept add-on therapy of
      rheumatoid arthritis.
AB  - BACKGROUND: Abatacept is a soluble fusion protein approved as add-on drug in
      rheumatoid arthritis. MAIN OBSERVATIONS: Here we report the first case of fixed
      drug eruption followed by lichen aureus due to abatacept in a 67-year-old woman.
      CONCLUSION: Fixed drug eruption is an unexpected drug reaction for abatacept,
      since T-cell activation is inhibited.

PMID- 21886714
TI  - Dermoscopy findings of alopecia areata in an African-American patient.
AB  - BACKGROUND: Dermoscopy has been established as an indispensable tool in the
      diagnosis and follow up of hair disorders. In alopecia areata, dermoscopy of
      active disease shows yellow dots, dystrophic hairs, as well as cadaverized (black
      dots) and exclamation mark hairs. Alopecia areata has been reported to occur
      equally among races, however, until date, there are no published data regarding
      dermoscopic findings in African-American patient. MAIN OBSERVATION: We report a
      case of scalp dermoscopy of alopecia areata in an African-American patient that
      shows a diffuse honeycomb-like pigmented network, few yellow dots and white dots.
      CONCLUSION: This case shows that skin color may affect dermoscopic findings in
      alopecia areata. In our African-American patient with alopecia areata dermoscopy
      showed a diffuse honeycomb-like pigmented network, which was previously
      considered characteristic for androgenic alopecia and white dots, which were
      considered characteristic for cicatricial alopecia. Further studies are needed to
      elucidate the presence of white dots in alopecia areata.

PMID- 21886715
TI  - In vivo reflectance confocal microscopy: usefulness for diagnosing hair diseases.
AB  - BACKGROUND: Reflectance confocal laser scanning microscopy (R-CSLM) is a new
      diagnostic technique which allows visualization of "optical intersections" within
      the epidermis and superficial layers of the dermis. Outlines of cells and their
      architecture are imaged and may be analyzed both horizontally and vertically to
      the skin surface. The method proved useful in early melanoma detection. We
      evaluated the potential usefulness of this method in a short series of patients
      with hair diseases. MAIN OBSERVATIONS: Two healthy persons and 6 patients with
      hair diseases (1 with alopecia areata, 1 with androgenic alopecia and 4 with
      genetic hair shaft abnormalities) were examined with the use of Vivascope 1500.
      In all patients one scalp location and one location in the mid forearm were
      evaluated. R-CSLM examination gave in all cases high quality images of the hair
      shaft intersections, at 1um intervals, which allowed detailed analysis of the
      hair structure. Hair follicles could be partly visualized at a depth of up to
      200um, which allowed analysis of only superficial parts of the hair follicles. An
      additional hurdle was bright reflection within the follicular ostia, which
      decreased the perception of details in these images. Hair could be best
      visualized, when analyzed on flat surfaces. Receiving good quality images from
      convex surfaces on the scalp required additional effort from the patient (to not
      move) and from the physician (to obtain best possible fit of the "optic window"
      to the scalp). CONCLUSIONS: These preliminary data show that R-CSLM may develop
      into a valuable tool in evaluation of hair shaft diseases. Further development is
      needed to apply this technique in abnormalities of the hair follicle and the
      perifollicular area.

PMID- 21886716
TI  - Buschke-Lowenstein tumor.
AB  - BACKGROUND: Verrucous carcinoma of the skin and mucosa is an uncommon type of
      well-differentiated squamous cell carcinoma. When it is present in the genitoanal
      region the term used is Buschke-Lowenstein tumor. The human papillomavirus seems
      to be implicated in its aetiology. Treatment is controversial. Topical
      chemotherapy, radiotherapy, immunotherapy and radical surgery have been employed.
      MAIN OBSERVATIONS: We report a rapidly progressing penile verrucous carcinoma
      which was treated sucessfuly with conservative surgery and CO2 laser. CONCLUSION:
      Treatment with CO2 laser in combination with conservative surgery may be a
      therapeutic option in Buschke-Lowenstein tumor.

PMID- 21886717
TI  - Efficacy of ribavirin in a case of long lasting and disabling Gianotti-Crosti
      syndrome.
AB  - BACKGROUND: Gianotti-Crosti syndrome, also known as papular acrodermatitis of
      childhood, is an acrally distributed papular eruption occurring mostly in infants
      and young children. MAIN OBSERVATIONS: A six-year-old girl presented to us with
      four-month history of a generalized intensely pruritic rash, clinically
      consistent with Gianotti-Crosti syndrome, following a febrile illness with common
      cold symptoms. Clinical remission was not achieved despite of several
      medications. With reluctance and parent's informed consent, we commenced a course
      of oral ribavirin syrup at a dose of 300mg daily for five days. Dramatic
      symptomatic remission was noted five days later. CONCLUSION: Further studies are
      needed to confirm the efficacy of ribavirin in Gianotti-Crosti syndrome.

PMID- 21886718
TI  - Erythromelalgia accompanying rosuvastatin-associated myopathy.
AB  - BACKGROUND: Secondary erythromelalgia can occur due to various underlying medical
      disorders or drug toxicity. MAIN OBSERVATIONS: A 75-year old male developed acute
      secondary erythromelalgia following the onset of rosuvastatin use and associated
      myopathy. The illness was reversible after discontinuation of the pharmacological
      agent. CONCLUSION: Secondary erythromelalgia may occur after rosuvastatin use,
      but this and other dermatological toxicities are rare.

PMID- 21886720
TI  - Chronic venous ulceration with associated angiosarcoma.
AB  - BACKGROUND: Angiosarcoma is a malignant tumor of the blood vessels' endothelial
      lining. The tumor is very aggressive and tends to recur locally and metastasize
      to distant organs. Commonly, it is associated with different risk factors like
      lymphoedema, prior radiotherapy but rarely, it may also be associated with
      chronic venous ulceration. MAIN OBSERVATION: We present a patient with a chronic
      venous ulceration who developed angiosarcoma of the ulcerated leg with good
      outcome after treatment. CONCLUSION: It is very important to follow patients with
      chronic wounds and recognize changes which may be life threatening. In addition
      to squamous cell carcinoma (Marjolin's tumor), which is most common, angiosarcoma
      can develop within a venous ulcer.

PMID- 21886719
TI  - Malignant histiocytosis of the skin: a case report and review of the literature.
AB  - BACKGROUND: Malignant histiocytosis is a rare neoplasm composed of abnormal
      histiocytes typically affecting the liver, spleen, lymph nodes, and bone marrow.
      This entity has been rarely documented involving the skin and has never been
      reported confined to the skin. MAIN OBSERVATIONS: A 74-year-old white man
      presented to the dermatology clinic with complaints of a non-healing ulcerated
      lesion on his cheek of several months duration. Histopathological examination
      revealed a poorly circumscribed neoplasm consisting of pleomorphic epithelioid
      cells with abundant foamy cytoplasm. Immunohistochemistry was positive for CD-43,
      CD-68, and lysozyme, but negative for CD-3, CD-20, CD-30, CD-34, SMA, CD-1a or S
      100. The prominent CD-68 and lysozyme staining along with the histological
      features, the clinical presentation of erythematous nodules with diffuse
      erythematous plaques, and absence of bone marrow findings, led to the diagnosis
      of malignant histiocytosis confined to the skin. CONCLUSION: Malignant
      histiocytosis involving the skin is rare. The presence of large pleomorphic
      epithelioid cells with foamy cytoplasm, with or without engulfed erythrocytes
      should alert the dermatopathologist to the possibility of malignant
      histiocytosis. Appropriate immunohistochemical evaluation, including CD-43, CD
      68, CD-1a, S-100, and lysozyme, should be completed to confirm the diagnosis.

PMID- 21886721
TI  - Herpes zoster - associated erythema multiforme.
AB  - BACKGROUND: Erythema multiforme is a cutaneous reaction that has only rarely been
      described in varicella zoster virus infection. MAIN OBSERVATIONS: We describe a
      76-year old immunocompetent male patient with thoracic herpes zoster. While
      treated with oral brivudin he developed a widespread cutaneous erythema
      multiforme. The lesions completely cleared with two weeks with systemic
      corticosteroids. CONCLUSION: Varicella zoster infections are possible triggers of
      erythema multiforme and this is the oldest patient reported with such an
      association. Brivudin itself has not been reported to induce erythema multiforme
      and is an unlikely cause of disease in our patient.

PMID- 21886722
TI  - Trichoscopy (hair and scalp videodermoscopy) in the healthy female. Method
      standardization and norms for measurable parameters.
AB  - BACKGROUND: Trichoscopy is a newly developed method of hair image analysis, based
      on videodermoscopy of hair and scalp. OBJECTIVE: The aim of the study was to
      establish normal values and set the standard for trichoscopy in female
      population. PATIENTS AND METHODS: A total of 60 healthy females with no symptoms
      of hair or scalp diseases in anamnesis, upon clinical examination and in classic
      hair diagnostic techniques were included into the study. Mean age of these
      females was 36.5 (19-64) years. Trichoscopy was performed with the use of
      Fotofinder II. In all patients trichoscopy was performed in four locations
      (frontal area, occipital area, left and right temporal area). Hair and
      perifollicular area were evaluated. Measurements were performed with the
      application of the MoleAnalyzer software. RESULTS: Mean hair thickness was
      0.061mm+/-0.008mm in frontal area vs. 0.057mm+/-0.007mm in occiput (p<0,001) and
      vs. 0.058mm+/-0.008mm in left temporal area and 0.059mm+/-0.008mm in right
      temporal area (p>0.005). The percentage of thin hairs (below 0.03mm) was 5%+/-4.3
      in frontal area vs. 5.5%+/-4.8 in occiput vs. 6.4%+/-5.7 in right temporal area.
      The highest proportion of single-hair pilosebaceous units was observed in the
      temporal areas (29.1+/-16.2 vs. 23.2+/-13.5 in frontal and 18.4+/-12.1 in
      occipital areas; p<0.005). Based on study results, the norms for parameters
      measured in trichoscopy were assessed: mean hair thickness bigger than 0,053mm in
      frontal area and bigger than 0,050mm in others; percentage of thin hairs should
      be less than 10% in frontal and occipital area and less than 13% in temporal
      areas. The percentage of pilosebaceous units with single hair should be less than
      35% in frontal area, 30% in occiput and 40% in temporal areas. Yellow dots were
      seen sporadically and they shouldn't be in a higher number than 3 in 4 fields of
      vision with 70-fold magnification in frontal area and only 1 in others.
      Perifollicular discoloration should be lower than 25% for frontal area, lower
      than 15% in occiput and 20% for temporal areas. CONCLUSION: A standard procedure
      to perform trichoscopy (hair and scalp videodermoscopy) for diagnostic purposes
      was developed. Norms of measurable parameters were established for the population
      of adult white females.

PMID- 21886723
TI  - Development of pyoderma gangrenosum during therapy with infliximab.
AB  - BACKGROUND: Pyoderma gangrenosum is a rare inflammatory disease of unknown
      etiology and a poorly understood pathogenesis. Its clinical presentation is
      variable and a large percentage of cases are associated with inflammatory bowel
      diseases. Peristomal pyoderma gangrenosum represents a variant of the diseases,
      occurring in patients with colostomy. Multiple cases demonstrate efficacy of
      infliximab and other anti-TNF-alpha drugs in treatment of pyoderma gangrenosum.
      MAIN OBSERVATIONS: A 47-year-old male with ulcerative colitis and proctocolectomy
      with ileal pouch reconstruction protected by ileostomy in the course of diseases
      received infliximab therapy together with azathioprine for his inflammatory bowel
      diseases. Six months after initiation of infliximab therapy the patient developed
      multiple pyoderma gangrenosum lesions on the trunk, abdomen, genitalia, gluteus,
      extremities, left preauricular region and peristomal area. After systemic
      corticosteroid therapy, combined with topical tacrolimus, the lesions slowly
      improved. Seven months later, during ongoing infliximab therapy, the patient
      developed a sepsis with fatal outcome. CONCLUSION: Constant trauma generated by
      colostomy may be a contributing factor to the development and persistence of
      pyoderma gangrenosum. It may be hypothesized that this patient developed pyoderma
      gangrenosum despite infliximab or that pyoderma gangrenosum may represent a rare
      adverse effect of the drug.

PMID- 21886724
TI  - Painful, slow developing abscesses. Furuncular miyasis due to double skin
      infestation by Dermatobia hominis.
AB  - BACKGROUND: Myiasis is defined as invasion of tissues by Diptera flies. The
      condition is endemic in the forested areas of Mexico, Central and South America.
      MAIN OBSERVATIONS: A 61-year-old woman presented with two boil-like inflammatory
      and painful lesions on her back. She had been travelling in Central America.
      Biopsies revealed a myiasis with mature third instar larvae of Dermatobia
      hominis, a diptera fly endemic in this region. Complete surgical excision and
      systemic antibiosis led to a delayed but complete healing. CONCLUSION: We
      presented a patient with a double infestation by Dermatobia hominis.
      Dermatologists should be aware of this disease, which has become increasingly
      common in travellers and is seen now also in unusual regions, other than Central
      and South America.

PMID- 21886725
TI  - Cutaneous cholesterol embolization.
AB  - BACKGROUND: Cutaneous cholesterol embolization syndrome occurs as a result of
      cholesterol embolization from atherosclerotic plaques lining the walls of
      arteries and arterioles. It can occur sporadically but is more commonly
      associated with iatrogenic manipulation via invasive vascular procedures or
      therapies (anticoagulation or thrombolytics) The three most common organ systems
      afflicted by cholesterol emboli include the kidneys, gastrointestinal system, and
      skin. MAIN OBSERVATIONS: We present two patients with cutaneous cholesterol
      embolization A 74-year-old with no prior disease or trauma was referred to the
      hospital with the acute chest pain. After 24-48 he developed livedo reticularis,
      followed by necrotic areas like bilaterally on hips and in the lumbar region. The
      second patient, 69-year-old man with a history of hyperglycemia, hyperlipidaemia,
      and hypertension was referred with weight loss, bilateral livedo reticularis,
      severe pain of lower extremities and impaired renal function. The toes first
      became cyanotic and than skin necrosis developed. Skin biopsy revealed presence
      of cholesterol clefts in the lumina of small arteries and arterioles. In both
      patients the necrotic skin and subcutaneous tissue had been debrided. Daily
      dressing was applied and tissue defects underwent secondary healing. CONCLUSION:
      The diagnosis of cholesterol embolization relies on clinical and histologic
      examination. Both, diagnosis and treatment needs a multidisciplinary approach,
      especially in cases of multi-organ involvement.

PMID- 21886726
TI  - Mycosis fungoides and CD30+ cutaneous T-cell lymphoma simulating pyoderma
      gangrenosum in a patient with ulcerative colitis.
AB  - BACKGROUND: Pyoderma gangrenosum is estimated to occur in 5% to 12% of ulcerative
      colitis patients. Primary CD30+ cutaneous large cell lymphoma is the second most
      common cutaneous lymphoma. It may coexists with mycosis fungoides. MAIN
      OBSERVATIONS: We report a 38-years-old female patient with 12 year history of
      ulcerative colitis, treated previously with 5-aminosalicylic acid and systemic
      corticosteroids. The disease has been in remission for the past 1.5 years, with
      no maintenance treatment. The patient then developed a rapidly progressing
      ulcerated lesion clinically simulating pyoderma gangrenosum. Physical examination
      revealed also a small number of hairless hypopigmented patches on the upper and
      lower limbs which she claimed to have appeared 4 years ago. Surprisingly a
      histological evaluation of the ulcer revealed a CD30+ primary cutaneous large
      cell lymphoma, while histology of hypopigmented lesions revealed mycosis
      fungoides, patch stage. T-cell receptor gene rearrangement from the two lesions
      didn't reveal the same T Cell clonalitiy and the patients lymphoma was stable.
      CONCLUSION: Our case presents the rare coexistence of primary mycosis fungoides
      and primary CD30+ cutaneous large cell lymphoma, rather than the CD30+ cutaneous
      large cell lymphoma developing from mycosis fungoides. This case also presents
      the development of a pyoderma gangrenosum-like lesion of CD30+ cutaneous large
      cell lymphoma in a patient with ulcerative colitis. An observation that
      emphasizes the need for a high index of suspicion in cases diagnosed as pyoderma
      gangrenosum based solely on clinical appearance.

PMID- 21886727
TI  - Neonatal Norwegian scabies: three cooperating causes.
AB  - BACKGROUND: Norwegian or crusted scabies is seldom reported in infancy, usually
      in immune deficient patients. MAIN OBSERVATIONS: We report a case of an infant
      affected by atopic dermatitis since birth. The patient was ineffectively treated
      with topical and systemic steroids for several weeks for the insurgence of
      cutaneous xerosis and erithema. Clinical inspection and optical microscopic
      examination of skin scraped scales leaded to the diagnosis of crusted scabies.
      The physiological inability to scrapping reaction, the immunological profile
      deriving from atopy and finally iatrogenic immunodepression cooperating to
      conduce to crusted scabies. CONCLUSION: In our case iatrogenic immunosuppression,
      atopic dermatitis and the absence of skin scraping reaction because of the very
      young age might have contributed to the unusual presentation of scabies. This
      case suggests considering possible alternative diagnosis of scabies in the
      failure of the treatment for atopic eczema.

PMID- 21886728
TI  - Dermoscopy of eccrine poroma with calcification.
AB  - BACKGROUND: Eccrine poromas are relatively common slow-growing benign solitary
      adnexal tumors originating from the intraepidermal portion of the eccrine sweat
      duct (acrosyringium). Dystrophic calcification is rarely found in lesions of
      eccrine poroma, and only 2 cases of eccrine poroma with calcification have been
      reported thus far. In the present report, we describe another case of eccrine
      poroma with calcification occurring in the palm of the hand. Also, we show
      dermoscopic features of this case. MAIN OBSERVATIONS: A 73-year-old man with
      hemiparesis, who had a 10-year history of tumor on his right palm, which was
      occasionally injured by a walking crutch, causing bleeding and ulceration.
      Physical examination revealed a pigmented dome-shaped tumor. Dermoscopic analysis
      revealed glomerular vessels, multiple pink-white structureless areas, and
      lacunae. Histological examination revealed that the tumor was composed of cords
      of tumor cells extending from the epidermis into the dermis. These were uniformly
      cuboidal cells with round, basophilic nuclei and dense vascular stromas with
      telangiectasia. The tumor showed cystic structures and calcification. The patient
      was diagnosed with Pinkus-type eccrine poroma on the basis of histological
      findings. CONCLUSIONS: Although cutaneous neoplasms commonly associated with
      calcification are of follicular origin, it is known that dystrophic calcification
      may be triggered also in tumors of eccrine origin by multiple factors, including
      mechanical injury. Dermoscopy may be helpful in establishing clinical diagnosis
      of calcified eccrine poromas.

PMID- 21886729
TI  - Acquired acrodermatitis enteropathica due to zinc deficiency in a patient with
      pre-existing Darier's disease.
AB  - BACKGROUND: Acrodermatitis enteropathica is characterised by inflamed patches of
      dry red skin which then become crusted and blistered before revealing a pustulent
      eroded lesion. Typically these patches start near the body's orifices before
      migrating to other sites, however in this patient the presentation was atypical
      thus delaying the diagnosis. OBSERVATIONS: We report a case of an atypical
      presentation of acrodermatitis enteropathica (AE) due to acquired zinc deficiency
      in a 65 year old female patient with a previous diagnosis of histologically
      confirmed Darier's disease. This patient's rash began on the limbs and trunk
      before progressing to include the perineum, oral mucosa and nose. Diffuse loss of
      hair on scalp, eyebrows and eyelashes was observed. Acrodermatitis enteropathica
      typically presents in infants, either due to an autosomal recessive genetic
      disorder, or after the cessation of breast feeding. In adults acquired zinc
      deficiency can be caused by glucagonoma syndrome, poor nutritional state,
      intestinal malabsorption, nephrotic syndrome and after major trauma (i.e. burns
      or significant surgery). In our patient low zinc levels confirmed hypozincaemia
      and the diagnosis of acrodermatitis enteropathica. The patient started oral zinc
      replacement. Within a few days her symptoms began to improve, and her hair has
      started to grow. CONCLUSION: We believe this to be an unusual presentation of
      acrodermatitis enteropathica due to a probable dietary zinc deficiency in a lady
      with pre-existing Darier's disease which may possibly have influenced the
      uncharacteristic clinical presentation.

PMID- 21886730
TI  - Erythema multiforme-like lesions in the course of infectious mononucleosis.
AB  - BACKGROUND: The rash in infectious mononucleosis is usually diffusely macular.
      MAIN OBSERVATIONS: A 15-year-old boy presented to us with high grade fever, sore
      throat, malaise, body aches, and polyarthralgia. He developed annular,
      erythematous, and non-scaly eruptions on chest and right arm. Blanching erythema
      was noted on his trunk. He had bilateral tender cervical lymph nodes, severe
      pharyngeal congestion, petechiae on soft palate, uvular edema, infraorbital
      edema, and marginal tender hepatomegaly. Investigations revealed lymphocytosis
      and activated atypical lymphocytes in the peripheral smear, and positive monospot
      test. The boy subsequently recovered in one week with total disappearance of his
      rash. Epstein-Barr virus-related infectious mononucleosis was considered the most
      likely diagnosis for our patient. CONCLUSIONS: To our knowledge, this atypical
      case is the third reported case of annular lesions in infectious mononucleosis.
      Dermatologists and other clinicians should be alerted to this special
      presentation of primary EBV infection.

PMID- 21886732
TI  - Psoriasis of the lips.
AB  - BACKGROUND: Psoriasis is a frequently occurring disorder with a chronic and
      relapsing course. Common sites of involvement are the extremities, trunk, scalp
      and nails. The disease may occasionally involve genitalia and the anus. Although
      cutaneous lesions are generally sufficiently distinct to make a diagnosis,
      diagnostic difficulties can be found in cases of unusual involvement. MAIN
      OBSERVATIONS: We report a 38-year-old man who presented scaling and cracking of
      the lips without intraoral involvement as a first manifestation of psoriasis.
      Three years later he developed erythematous plaques with desquamation on fingers,
      characteristic of psoriasis. CONCLUSION: Psoriasis should be considered in the
      differential diagnosis of chronic or recurrent labial lesions.

PMID- 21886731
TI  - Chronic desquamative gingivitis and oral health-related quality of life.
AB  - BACKGROUND: Chronic desquamative gingivitis is a clinical description of the
      gingiva which is often a presenting manifestation of dermatoses or mucocutaneous
      disorders. The patients often experience oral discomfort and pain, which can
      significantly compromise their life qualities. MAIN OBSERVATIONS: Here we present
      a case of chronic desquamative gingivitis in a 77-year-old woman with
      periodontitis. After establishment of oral hygiene, initial periodontal therapy
      including topical steroid application was performed. Subsequent periodontal
      surgery resulted in further reduction of local inflammation. These interventions
      lead to a significant improvement in gingival lesions as well as oral health
      related quality of life. CONCLUSIONS: Chronic desquamative gingivitis is often a
      presenting manifestation of dermatoses or mucocutaneous disorders. Correct and
      early diagnosis is important. Management of inflammatory conditions including
      periodontitis can contribute to the clinical resolution of chronic desquamative
      gingivitis and improve life quality of the patient. A greater awareness of this
      condition among dentists and dermatologists would be helpful in providing patient
      centered care.

PMID- 21886733
TI  - Papillon-lefevre syndrome.
AB  - BACKGROUND: Papillon-Lefevre syndrome is a rare autosomal recessive disorder
      caused by cathepsin C gene mutation leading to the deficiency of cathepsin C
      enzymatic activity. The disease is characterized by palmoplantar hyperkeratosis,
      loss of deciduous and permanent teeth and increased susceptibility to infections.
      Onset of palmoplantar hyperkeratosis and periodontopathy is most commonly before
      the age of 4 years. MAIN OBSERVATIONS: A 15 year old boy with a history of
      frequent infections presented with hyperkeratosis of palms and soles, which
      worsened during winter season. Examination of the oral cavity revealed missing
      mandibular central incisors and left lateral incisors. Most remaining permanent
      teeth were mobile. Fibrosis and scarring of gingival and labial mucosa restricted
      opening of the mouth. CONCLUSION: Early diagnosis of Papillon-Lefevre syndrome
      may help preserve the teeth. We present a case of a late diagnosis of this
      syndrome.

PMID- 21886734
TI  - Klippel-Trenaunay Syndrome: a case report with brief review of literature.
AB  - BACKGROUND: Klippel-Tranuanay Syndrome is a rare sporadic disease characterized
      by clinical triad of capillary malformation; soft tissue and bony hypertrophy;
      and atypical varicosity. Although this syndrome was first described more than
      hundred years ago, exact incidence has not been estimated yet. Several theories
      have been postulated to describe its pathogenesis. Clinical presentation of this
      syndrome is protean ranging from minimal asymptomatic disease to life threatening
      bleeding and embolism. Management of this syndrome includes careful diagnosis,
      prevention and treatment of complications. MAIN OBSERVATION: We are presenting a
      case of Klippel-Tranuanay Syndrome in a 19-year-old male patient presenting with
      varicosity in lateral aspect of right leg. On careful examination other
      components of the syndrome were found. Patient was kept on yearly follow up.
      CONCLUSION: Usually patients with Klippel-Tranuanay Syndrome present with
      complication. This case shows that there is also a need for medical solutions in
      patients who seek advise for cosmetic reasons.

PMID- 21886735
TI  - A case of psoriasis worsened by atorvastatin.
AB  - Statins are known to have a number of cutaneous adverse effects including the
      induction of autoimmune diseases like systemic and subacute lupus erythematosus,
      dermatomyositis, polymyositis, lichen planus pemphigoides and the drug reaction
      with eosinophilia and systemic symptoms (DRESS). Statins have been also reported
      as a triggering factor of psoriasis. We report a case of psoriasis vulgaris that
      worsened three months after atorvastatin was introduced and improved after its
      discontinuance.

PMID- 21886736
TI  - A case of atrophoderma vermiculatum responding to systemic isotretinoin.
AB  - BACKGROUND: Atrophoderma vermiculatum is a rare, benign follicular disorder that
      primarily affects children. It is characterized by symmetric reticular or
      honeycomb atrophy of the cheeks that may extend to the ears and forehead. The
      defect is believed to be due to abnormal keratinization in the pilosebaceous
      follicle. Management of atrophoderma vermiculatum is challenging. MAIN
      OBSERVATIONS: We report the case of a 10-year-old boy, diagnosed as atrophoderma
      vermiculatum. The boy underwent two 6-month treatment courses with isotretinoin
      at a dose of 0.50mg/kg/day, which resulted in partial remission of the lesions.
      Even though the disease did not completely regressed, isotretinoin stopped
      atrophy progression and improved cosmetic appearance of the skin. CONCLUSIONS: In
      this case of a child with atrophoderma vermiculatum isotretinoin stopped atrophy
      progression and improved cosmetic appearance of the skin. No adverse events were
      observed. However, always, when applying isotretinoin in children, it has to be
      considered that, apart from possible common adverse events, this treatment may
      promote premature epiphyseal plate closure and may stop normal growth in some
      children.

PMID- 21886737
TI  - Unilateral aquagenic keratoderma treated with botulinum toxin A.
AB  - BACKGROUND: Aquagenic keratoderma is a rare transient disease that occurs after
      water immersion and disappears shortly after drying. Most cases involve the palms
      and fingers bilaterally but it can also affect the soles. Few cases have been
      associated with drugs but its pathogenesis remains unclear. MAIN OBSERVATION: We
      report a 60-year-old man with a 30-year-history of aquagenic keratoderma of the
      right palm without associated hyperhidrosis or history of drug intake. After
      unsuccessful treatment with 15% aluminium chloride hexahydrate gel, botulinum
      toxin A injections led to significant improvement within 2 weeks. CONCLUSIONS: To
      our knowledge, this case is the first report of idiopathic unilateral aquagenic
      keratoderma in the medical literature. It is the third report of successful
      treatment with botulinum toxin A which is in favor of a role of sweat glands in
      the pathogenesis of aquagenic keratoderma.

PMID- 21886738
TI  - Sporadic familial ulnar hexadactyly of all four limbs.
AB  - BACKGROUND: Polydactyly belongs to skeletal anomalies and may be a symptom of
      more complex genetic syndromes. MAIN OBSERVATION: We observed an index case of
      ulnar hexadactyly of all four limbs in a 20-year-old man from India with three
      more brothers affected in his family. No additional anomalies were observed. The
      diagnosis of a sporadic (ulnar) postaxial hexadactyly was made. CONCLUSION:
      Sporadic postaxial hexadactyly is one of the most common polydactylies in humans.
      In contrast, in the dermatologic literature the condition has only rarely been
      described. CONCLUSION: Presence of supernummary digits or toes, i.e. polydactyly,
      is seen occasionally in the dermatologic practise. The present case is
      extraordinary since all limbs were involved and the same was true for three of
      his brothers. If treatment is asked, hand surgery would be necessary.

PMID- 21886739
TI  - Stevens-Johnson syndrome associated with cytomegalovirus infection in a child
      with ependymoma.
AB  - BACKGROUND: Stevens-Johnson syndrome is an uncommon, acute life-threatening
      disease characterized by extensive epidermal sloughing and mucositis. In
      childhood, as in adulthood, this condition is mostly related to drugs, in
      particular antibiotics. Only a few cases reported were firmly attributed to
      infectious agents, mainly Mycoplasma pneumonia but the causative role of
      infectious microorganisms seems particularly relevant in pediatric patients. The
      seriousness of this condition imposes a prompt recognition and the early
      withdrawal of the potential causative drugs or the institution of directed
      measures against infectious agents (depending on the suspected etiology), as well
      as a supportive and more specific therapy. Some treatments claim to halt the
      progression of skin detachment, but remain of unproven benefit due to the lack of
      prospective, well controlled, randomized clinical trials. MAIN OBSERVATIONS: We
      report a case of a 2-year-old boy admitted in our hospital for the treatment of
      an ependymoma of the posterior fossa, who developed a Stevens-Johnson syndrome
      associated most probably with a cytomegalovirus infection. He was successfully
      treated with high dose intravenous immunoglobulin and gancyclovir. CONCLUSION: To
      the best of our knowledge, this is the first case of SJS associated with CMV
      infection.

PMID- 21886740
TI  - Alopecia areata developing paralell to improvement of psoriasis during
      ustekinumab therapy.
AB  - BACKGROUND: Ustekinumab is a new immunosuppressive anti-psoriasis agent. The drug
      targets the p40 subunit of IL-12 and IL-23 and indirectly inhibits cytokine
      production by Th17 cells. MAIN OBSERVATIONS: We present a case of a 36-year-old
      male patient with psoriasis, who received ustekinumab therapy, applied in 45mg
      subcutaneous injections at week 0, 4 and than every 12 weeks. After 7 months of
      therapy PASI decreased from 10,1 to 0,9. At this phase of therapy he developed
      two patches of alopecia areata on the scalp. The diagnosis was made based on
      clinical appearance and was confirmed by trichoscopy (hair and scalp dermoscopy)
      and reflectance confocal microscopy. The development of alopecia areata was
      preceded by emotional stress and dental infection. CONCLUSIONS: Ustekinumab seems
      an unlikely cause of alopecia areata in this patient. However, lack of efficacy
      is preventing hair loss may indicate that interleukin- 12 cytokine family is not
      a key player in pathogenesis of alopecia areata.

PMID- 21886741
TI  - A case of atypical pyoderma gangrenosum.
AB  - BACKGROUND: Pyoderma gangrenosum is a rare inflammatory disease of unknown
      etiology and unspecific histopathology. There are no clear-cut criteria for the
      diagnosis of this disease. The diagnosis is usually made based on clinical
      appereance, course of disease and possible, commonly coexisting disorders. In
      atypical cases the diagnosis is based on exclusion of other causes of similar
      appearing cutaneous ulcerations. MAIN OBSERVATIONS: The 67-year-old male patient,
      presented with a 15-year history of painful ulcers and vegetative lesions covered
      with sero-hemorrhagic and purulent secretions, localized on the dorsal surface of
      both hands leading to self-amputation of distal phalanges. We report a step-by
      step The patient refers to have these complaints for more than 15 years. An
      extensive diagnostic procedure led to the diagnosis of pyoderma gangrenosum as a
      diagnosis of exclusion. CONCLUSION: This report shows an atypical variant of an
      ulcerative disease. Pyoderma gangrenosum, a diagnosis of exclusion, was sustained
      based on an extensive diagnostic procedure. In this article we describe the step
      by-step approach which let to this diagnosis.

PMID- 21886742
TI  - A huge infiltrating squamous cell carcinoma of the neck 46 years after
      radiotherapy of a haemangioma.
AB  - BACKGROUND: There is a higher risk for malignant tumours in patients who
      underwent any kind of radiotherapy. MAIN OBSERVATIONS: An 87-year-old patient
      with an extended squamous cell carcinoma of the neck was referred to our
      hospital. The large ulcerated tumour showed a deep infiltration of the para
      vertebral muscles and the spinal processes C6-C7. The tumour was known since
      about six years and appeared about 46 years after low-dose radiotherapy of a
      cervical haemangioma of the neck in 1961. The large dimension of the tumour
      leaded to a radical surgical removal and a sufficient fast reconstruction
      strategy. The extended defect was covered by a pedicled lower musculocutaneous
      trapezius flap. No postoperative complications like partial necrosis, infection
      or movement disorders of the shoulder or a shoulder drop syndrome were seen. Ten
      weeks after the operation the patient showed a good functional and aesthetic
      result with no limitation of arm mobility. Two and a half years after radical
      intended surgery the patient was still alive and showed no recurrence of the
      tumour. CONCLUSIONS: In conclusion there is a need for a life-time lasting
      dermatological supervision in patients with a history of radiotherapy in the
      past, because the handling of patients with such an enlarged tumour is
      complicated.

PMID- 21886743
TI  - Multiple eruptive clear cell acanthoma.
AB  - BACKGROUND: Clear cell acanthoma is a rare solitary benign epidermal tumor of
      unknown etiology. The disease arises in the middle-age, with no sex predominance.
      It appears as a single reddish papule or papule-nodule and a peripheral scaling
      collarette is characteristic. Although solitary lesions are the rule, less than
      30 cases of multiple Clear cell acanthoma have been described in the literature
      to date. MAIN OBSERVATIONS: We report an unusual case of a healthy 74-year-old
      male with multiple clear cell acanthoma on the lower extremities treated
      successfully with cryotherapy. CONCLUSIONS: Despite significant progress in
      treatment of clear cell acanthoma, cryotherapy, based on liquid nitrogen, remains
      an important alternative in treating multiple clear cell acanthomas.

PMID- 21886744
TI  - Cinnamon contact stomatitis.
AB  - BACKGROUND: Cinnamon contact stomatitis (CCS) is a rare reaction to the use of
      products containing artificial cinnamon flavor ingredients. Such products are
      gums, toothpastes and mouthwashes. MAIN OBSERVATIONS: A 20-year-old female
      patient presented with white elevated mucosal patches in the right lateral board
      of her tongue. Based on anamnesis, the intitial diagnosis of allergy to cinnamon
      gum was established. Clinical differential diagnosis included hairy leukoplakia,
      leukoplakia and lichenoid reaction. The patient was advised to completely avoid
      the use of cinnamon flavoured chewing gums. On re-examination later she had a
      normal tongue appearance. CONCLUSIONS: Clinicians who treat patients with oral
      conditions should be aware of CCS in order to be able to correctly diagnose and
      manage this condition.

PMID- 21886745
TI  - Parry-Romberg syndrome.
AB  - BACKGROUND: Parry-Romberg syndrome (PRS) or idiopathic hemifacial atrophy is a
      rare neurocutaneous syndrome. It is characterized by slowly progressive atrophy,
      located on one side of the face, primarily involving the skin, fat and connective
      tissue. PRS seems to overlap with "en coupe de sabre" morphea. MAIN OBSERVATIONS:
      We present a case of hemifacial atrophy in a 14-year-old boy treated with topical
      calcipotriol-betamethasone ointment. The diagnosis of PRS was established mainly
      based on the clinical findings and histological picture. The time to diagnosis
      was almost 9 years, similar to the mean time reported in the literature.
      CONCLUSIONS: Understanding the pathogenesis and stopping disease progression is
      important as it can cause severe disfigurement and has neurological and
      psychiatric complications. Not much is known about the efficacy of agents used in
      the treatment of this syndrome making treatment decision very difficult. Possible
      complications, pathophysiology and therapeutic options are being discussed.

PMID- 21886746
TI  - Childhood linear IgA bullous disease induced by trimethoprim-sulfamethoxazole.
AB  - BACKGROUND: Linear IgA bullous disease (LABD) is a rare mucocutaneous autoimmune
      subepidermal blistering disease that can affect children mostly of pre-school
      age. As many as two-thirds of LABD are related to drug ingestion, particularly
      certain antibiotics, non-steroidal anti-inflammatory drugs and diuretics. MAIN
      OBSERVATION: We describe a 3-year-old boy who presented a CMV infection followed
      by LABD induced by trimtheporim-sulfametoxazole. To our knowledge, this is the
      first reported case of trimethoprim-sulfamethoxazole that was confirmed by a
      rechallenge. CONCLUSIONS: Most cases of drug-induced LABD are patients being
      treated with multiple systemic drugs that could induce the LABD. In the lack of
      suitable alternative treatment, the identification of the causative drug can be
      achieved by a rechallenge under close medical surveillance.

PMID- 21886747
TI  - Atypical "allergic crease".
AB  - BACKGROUND: The allergic crease (nasal crease) is a transverse line, common among
      patients who suffer from allergic rhinitis. Although it is a very prevalent
      condition, the skin manifestations which accompany this condition have been only
      sparsely reported. MAIN OBSERVATION: We describe an 18-year-old man with allergic
      rhinitis, who developed cornified papules along an allergic crease. Dermoscopic
      examination revealed oval, slightly raised, gray, sharply demarcated papules.
      Histopathology revealed seborrheic keratosis like hyperplasia, accompanied by
      horn cysts. CONCLUSIONS: To our knowledge, cornified papules have not been
      reported previously along the allergic crease. Considering the fact that allergic
      rhinitis is a common chronic condition of childhood, increased awareness of the
      skin manifestations which accompany this condition is essential.

PMID- 21886748
TI  - Lichen sclerosus of the oral cavity. Case report and review of literature.
AB  - BACKGROUND: Lichen sclerosus is a chronic muco-cutaneous inflammatory disorder of
      uncertain etiology. The prevalence of lichen sclerosus affecting only the oral
      mucosa is extremely rare and only 26 cases with histologically verified oral
      lichen sclerosus have been reported. MAIN OBSERVATIONS: A 60-year-old man was
      referred to our hospital for complaints of white lesions in the oral cavity,
      which was otherwise asymptomatic and did not have any cutaneous or anogenital
      lesions. Clinical examination revealed white patches with reddish areas on the
      buccal mucosa bilaterally and on the maxillary posterior gingiva. Microscopic
      analysis of the lesion showed atrophied epithelium with basal cell degeneration,
      hyalinized connective tissue stroma with minimal chronic inflammatory cell
      infiltrate. Verhoeff's staining revealed scantiness of elastic fibers in the
      connective tissue stroma. On the basis of these histological findings, the final
      diagnosis was given as Lichen Sclerosus. LS is rare in the oral cavity,
      particularly in the absence of simultaneous cutaneous and anogenital lesions.
      CONCLUSIONS: Only 7 cases of oral LS have been reported involving the gingiva. To
      our knowledge, this is the eigth case to be reported with gingival involvement
      and the first case to be reported with bilateral involvement of buccal mucosa and
      gingiva.

PMID- 21886749
TI  - Multiple eruptive periungual pyogenic granulomas during anti-CD20 monoclonal
      antibody therapy for rheumatoid arthritis.
AB  - BACKGROUND: New targeted therapies have been developed for inflammatory and
      neoplastic diseases. MAIN OBSERVATION: We report on a 73-year-old woman who
      developed multiple eruptive periungual and subungual pyogenic granulomas. Because
      of severe rheumatoid arthritis the patient was treated with monoclonal anti-CD20
      antibodies. Eruptive granuloma pyogenicum developed after the second antibody
      application and remained more than 8 weeks after targeted therapy was over. New
      lesions, however, did not appear. CONCLUSION: Eruptive granuloma pyogenicum of
      the nail apparatus is a possible new rare adverse effect of targeted therapies.
      To the best of our knowledge this is the first case in association with anti-CD20
      antibody treatment.

PMID- 21886750
TI  - Using an advanced radiation therapy technique for T4 squamous cell carcinoma of
      the face.
AB  - BACKGROUND: Patients with locally advanced skin cancer often present an uncommon
      and unique treatment challenge. Surgical resection and reconstruction with an
      acceptable cosmetic outcome is difficult for larger lesions with deep
      infiltration into subcutaneous tissues. Radiation therapy has been shown to be an
      effective treatment modality for advanced non-melanoma skin cancers, with cure
      rates ranging 50-100%. In this case report, we discuss the efficacy and outcome
      of treatment using an advanced radiation therapy technique to a large T4 squamous
      cell carcinoma of the face. MAIN OBSERVATIONS: The patient responded favorably to
      the advanced radiation treatment course, and achieved a clinical complete
      response to therapy. No further intervention was required. Advanced radiation
      therapy techniques offered treatment advantages that resulted in greater tumor
      dose escalation and minimizing of patient morbidity. CONCLUSIONS: Patients with
      advanced skin cancers of the head and neck should be considered for definitive
      radiation therapy using advanced treatment techniques. The use of definitive RT
      only for tumors deemed unresectable, or for inoperable patients at presentation
      deserves reconsideration. Further investigation is warranted.

PMID- 21886751
TI  - Schnitzler syndrome with cold-induced urticaria.
AB  - BACKGROUND: Schnitzler syndrome encompasses monoclonal gammopathy, urticaria,
      inflammation, recurrent fever, bone pain and arthralgia, with occasional
      lymphadenopathy and/or hepatosplenomegaly. It is a rare condition with
      approximately 100 cases reported in the literature. To our knowledge, this is the
      first reported case of cold-induced physical urticaria with Schnitzler syndrome.
      MAIN OBSERVATIONS: A 43-year-old woman presented to an allergy and immunology
      clinic with a 7 year history of chronic urticaria, angioedema with anaphylaxis,
      monoclonal gammopathy and bone pain. Her urticaria was triggered by cooler
      temperatures and an ice cube test for cold induced urticaria was positive. In
      spite of aggressive therapies this patient remains symptomatic. CONCLUSIONS:
      Schnitzler syndrome is under-recognized, particularly variants of the classical
      description of Schnitzler syndrome. Other diseases, especially those of
      hematologic origin, should be ruled out. This condition is largely refractory to
      conventional therapies, although novel treatments, such as interleukin-1 receptor
      inhibitor, may show promise.

PMID- 21886752
TI  - Unilateral pityriasis rosea in a child.
AB  - BACKGROUND: Various atypical variants of pityriasis rosea were published in the
      literature. There are very few reports abour pityriasis rosea being unilateral.
      MAIN OBSERVATIONS: We present a female child who presented with acute onset of
      scaly eruptions clinically consistent with a diagnosis of pityriasis rosea,
      affecting only one side of the body involving waist, thigh, forearm and leg on
      right side. CONCLUSIONS: It is extremely unusual for pityriasis rosea to present
      the eruptions only on one side of the body. This case is presented here for its
      rarity in clinical practice.

PMID- 21886753
TI  - Geographic tongue treated with topical tacrolimus.
AB  - BACKGROUND: Geographic tongue, or benign migratory glossitis, is usually an
      asymptomatic inflammatory disorder of the tongue mucosa of unknown etiology. It
      is characterized by circinate, erythematous, ulcer-like lesions of the dorsum and
      lateral border of the tongue due to loss of filiform papillae of the tongue
      epithelium. Symptomatic treatments have not been evaluated rigorously. MAIN
      OBSERVATION: We describe herein two cases of adult patients with persistent and
      painful geographic tongue successfully treated with topical application of 0.1%
      tacrolimus ointment. CONCLUSION: To our knowledge, this is the first report of
      successful treatment with topical 0.1% tacrolimus for symptomatic geographic
      tongue. Clinical trials are needed to confirm the efficacy and the safety of
      topical tacrolimus in treating geographic tongue.

PMID- 21886754
TI  - Generalized molluscum contagiosum in an HIV patient treated with diphencyprone.
AB  - BACKGROUND: Diphencyprone is a universal contact immunotherapy. The mechanism of
      action is based on an induction of the delayed-type hypersensitivity.
      Diphencyprone has been used in various forms for treatments of recalcitrant and
      facial warts, and alopecia areata. However, this treatment modality has not been
      generally used in immunocompromised patients. MAIN OBSERVATION: The present
      report demonstrated the efficacy of diphencyprone immunotherapy on the treatment
      of generalized molluscum contagiosum in a human immunodeficiency virus (HIV)
      infected patient. Minimal and transient side effects including pruritus,
      postinflammatory hyperpigmentation and irritation were noted. CONCLUSION:
      Diphencyprone contact immunotherapy appears to be a possible alternative
      treatment of widespread molluscum contagiosum in immunocompromised patients.

PMID- 21886755
TI  - Cytological diagnosis of molluscum contagiosum with an unusual clinical
      presentation at an unusual site.
AB  - BACKGROUND: Molluscum contagiosum, is a common skin infection caused by a pox
      virus usually present as raised nodule with umbilicated centre. Cytologic
      diagnosis has been documented in very few case reports as the lesion is subjected
      to fine needle aspiration rarely and awareness of the cytological features of
      Molluscum contagiosum is limited. The cytological diagnosis is further
      challenging in clinically unsuspected lesions. MAIN OBSERVATIONS: A 45-year-old
      female patient presented with 10 months history of a nodular nipple lesion which
      ulcerated after local application of caustic pencil. There was no associated
      breast lump. Cheesy material was expressed from the ulcer on the nipple and crush
      smeared on slides for cytological evaluation. Cytology smears revealed nucleate
      and anucleate squames in an inflammatory background. Characteristic
      intracytopalsmic and extracytopalsmic molluscum bodies were seen. CONCLUSION: The
      nipple is an unusual site of presentation for Molluscum contagiosum. Ulcerated
      lesions are rarer. In the present case, the cytological examination facilitated
      the diagnosis in a clinically unsuspected case. Cytology can be a useful rapid
      diagnostic aid in planning the management of these patients and help in avoiding
      unnecessary biopsies.

PMID- 21886756
TI  - Homozygous frame shift mutation in ECM1 gene in two siblings with lipoid
      proteinosis.
AB  - BACKGROUND: The extracellular matrix protein 1 (ECM1) is a glycoprotein,
      expressed in skin and other tissues. Loss-of-function mutation in ECM1 causes a
      rare autosomal recessive disorder called lipoid proteinosis. Lipoid proteinosis
      is presented by varying degrees of skin scars, beaded papules along the eyelid
      margins, variable signs of hoarseness of voice and respiratory disorders. More
      than 250 cases of this disorder have been described in the literature, but
      occurrence of lipoid proteinosis in siblings is very rare. This study was
      designed to investigate the possible mutation causing lipoid proteinosis in a
      Pakistani family and to elaborate the scope of possible genetic changes, causing
      the genodermatosis in Pakistan. MAIN OBSERVATIONS: In this study, two siblings
      (12 and 9-years sisters) were presented with scaly itchy lesions on whole body,
      hoarse voice and macroglossia. Their deceased father had similar clinical
      manifestations but mother and younger brother were unaffected. Blood samples from
      clinically affected and unaffected family members were collected with informed
      consent. The coding region of ECM1 gene containing 10 exons were amplified and
      sequenced. Both the affected siblings were shown to have homozygous frame shift
      mutation by deletion of the nucleotide T at 507, codon 169, exon 6. This resulted
      in a frame shift from codon 169 and appearance of a premature stop codon at 177,
      causing formation of a mutated protein (176 amino acids) instead of normal ECM1
      protein (540 amino acids). CONCLUSION: A case of homozygous 62-bp insertion in
      ECM1 gene causing lipoid proteinosis has been reported in another Pakistani
      family. The current study presents a homozygous frame shift mutation supporting
      an unusual function of ECM1 protein and broadens the spectrum of disease-linked
      mutations in this rare case of genodermatosis in this region.

PMID- 21886757
TI  - Respiratory function in patients with pemphigus vulgaris - a small clinical
      study.
AB  - BACKGROUND: Pemphigus vulgaris belongs to a group of rare, autoimmune, blistering
      disorders, requiring intensive immunosuppressive therapy. Lung infections are
      common in patients with pemphigus vulgaris. OBJECTIVE: To evaluate pulmonary
      function in patients with pemphigus vulgaris, in order to detect possible factors
      that might predispose PV patients to lung damage. METHODS: Ten patients first
      diagnosed with severe pemphigus vulgaris and 10 healthy individuals,were included
      in the study. Pulmonary function testing, blood gas analysis and quantification
      of alpha1-antitrypsin serum levels were performed. RESULTS: Mild reduction of CO
      diffusing capacity was recorded, compared to the mean predicted normal value.
      DLCOSB (single-breath carbon monoxide diffusing capacity test) values did not
      significantly differ between patients with pemphigus vulgaris and healthy
      controls, while differences regarding DLCO/VA (VA: Alveolar Volume) were
      statistically significant. Alpha 1-antitrypsin serum levels were decreased
      (<2.0g/L) in 60% (6/10) of patients with pemphigus vulgaris and were found normal
      in none of the healthy controls. CONCLUSION: A mild reduction of pulmonary
      diffusing capacity was observed in patients with pemphigus vulgaris.

PMID- 21886758
TI  - Pyogenic granulomas during isotretinoin therapy.
AB  - BACKGROUND: A review of scientific literature reveals a sparse documentation of
      periungual pyogenic granulomas as an adverse effect of isotretinoin therapy MAIN
      OBSERVATIONS: Periungual pyogenic granulomas appeared in four patients receiving
      isotretinoin therapy for severe acne. Oral and topical antibiotic treatments were
      ineffective and all cases spontaneously resolved once isotretinoin is
      discontinued. CONCLUSION: This report demonstrates the idiosyncratic nature of
      this side effect. We suggest that, although infection is possible due to the
      transformed nature of the normally protective skin barrier, oral and topical
      antibiotic treatments appear ineffective. Pyogenic granulomas spontaneously
      resolve once isotretinoin is discontinued.

PMID- 21886759
TI  - Cowden syndrome.
AB  - BACKGROUND: Cowden syndrome is a rare genodermatosis charactarized by presence of
      multiple hamartomas. The aim of the study was to specify the clinical,
      therapeutic and prognostic aspects of Cowden syndrome. CASES REPORT: Our study
      included 4 patients with Cowden syndrome, 2 males and 2 females between 14 and 46
      years old. Clinical examination of the skin revealed facials papules (4 cases),
      acral keratosis (1 case), translucent keratotic papules (2 cases). Oral
      examination revealed papules (4 cases), papillomatosis (4 cases), gingival
      hypertrophy (4 cases) and scrotal tongue (2 cases). Investigations revealed
      thyroid lesions (2 cases), fibrocystic disease and lipoma of the breast in 1
      case, "glycogenic acanthosis" (1 case), macrocephaly (2 cases), dysmorphic face
      (1 case) and lichen nitidus (1 case). Oral etretinate and acitretine were
      temporary efficient in 2 patients. Topical treatment with tretinoin lotion
      resulted in some improvement in cutaneous, but not mucosal lesions in one
      patient. No cancer was revealed. CONCLUSION: The pathognomonic mucocutaneous
      lesions were found in all patients. However, no degenerative lesions have been
      revealed. A new association of Cowden syndrome with lichen nitidus was found.
      Treatment with oral retinoids was efficient on cutaneous lesions.

PMID- 21886760
TI  - Photoletter to the editor: A new variant of ichthyosis follicularis with alopecia
      and photophobia (IFAP) syndrome with coexisting psoriasiform lesions and
      palmoplantar keratoderma. IFAP-PPK syndrome?
AB  - IFAP is an acronym for a rare congenital ectodermal disorder characterized by
      ichthyosis follicularis, alopecia and photophobia. A recessive X-linked mode of
      inheritance was initially proposed but recent reports in girls suggested genetic
      heterogeneity of this syndrome. We herein describe a 1-year-old boy with clinical
      features typical of IFAP syndrome plus psoriasis-like lesions and palmoplantar
      keratoderma (PPK).

PMID- 21886761
TI  - Photoletter to the editor: Cutaneous myxoid fibroblastoma.
AB  - Cutaneous myxoid fibroblastoma is an extremely rare soft tissue tumor, diagnosed
      based on histopathology. The histopathological triad for the diagnosis of the
      disease includes 1) spindle-shaped and/or stellate cells with elongated nuclei
      and eosinophilic cytoplasm 2) distribution of cell in amyxoid stroma containing
      very fewcollagen fibers 3) cellular atypiawithout marked nuclear polymorphism in
      some cells. To date, only single cases of this disease have been reported. We
      report a new case and discuss the disease.

PMID- 21886765
TI  - Anticancer activities of six selected natural compounds of some Cameroonian
      medicinal plants.
AB  - BACKGROUND: Natural products are well recognized as sources of drugs in several
      human ailments. In the present work, we carried out a preliminary screening of
      six natural compounds, xanthone V(1) (1); 2-acetylfuro-1,4-naphthoquinone (2);
      physcion (3); bisvismiaquinone (4); vismiaquinone (5); 1,8-dihydroxy-3-geranyloxy
      6-methylanthraquinone (6) against MiaPaCa-2 pancreatic and CCRF-CEM leukemia
      cells and their multidrug-resistant subline, CEM/ADR5000. Compounds 1 and 2 were
      then tested in several other cancer cells and their possible mode of action were
      investigated. METHODOLOGY/FINDINGS: The tested compounds were previously isolated
      from the Cameroonian medicinal plants Vismia laurentii (1, 3, 4, 5 and 6) and
      Newbouldia laevis (2). The preliminary cytotoxicity results allowed the selection
      of xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone, which were then tested on a
      panel of cancer cell lines. The study was also extended to the analysis of cell
      cycle distribution, apoptosis induction, caspase 3/7 activation and the anti
      angiogenic properties of xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone.
      IC(50) values around or below 4 ug/ml were obtained on 64.29% and 78.57% of the
      tested cancer cell lines for xanthone V(1) and 2-acetylfuro-1,4-naphthoquinone,
      respectively. The most sensitive cell lines (IC(50)<1 ug/ml) were breast MCF-7
      (to xanthone V(1)), cervix HeLa and Caski (to xanthone V(1) and 2-acetylfuro-1,4
      naphthoquinone), leukemia PF-382 and melanoma colo-38 (to 2-acetylfuro-1,4
      naphthoquinone). The two compounds showed respectively, 65.8% and 59.6%
      inhibition of the growth of blood capillaries on the chorioallantoic membrane of
      quail eggs in the anti-angiogenic assay. Upon treatment with two fold IC(50) and
      after 72 h, the two compounds induced cell cycle arrest in S-phase, and also
      significant apoptosis in CCRF-CEM leukemia cells. Caspase 3/7 was activated by
      xanthone V(1). CONCLUSIONS/SIGNIFICANCE: The overall results of the present study
      provided evidence for the cytotoxicity of compounds xanthone V(1) and 2
      acetylfuro-1,4-naphthoquinone, and bring supportive data for future
      investigations that will lead to their use in cancer therapy.

PMID- 21886766
TI  - Evidence that gene activation and silencing during stem cell differentiation
      requires a transcriptionally paused intermediate state.
AB  - A surprising portion of both mammalian and Drosophila genomes are
      transcriptionally paused, undergoing initiation without elongation. We tested the
      hypothesis that transcriptional pausing is an obligate transition state between
      definitive activation and silencing as human embryonic stem cells (hESCs) change
      state from pluripotency to mesoderm. Chromatin immunoprecipitation for trimethyl
      lysine 4 on histone H3 (ChIP-Chip) was used to analyze transcriptional
      initiation, and 3' transcript arrays were used to determine transcript
      elongation. Pluripotent and mesodermal cells had equivalent fractions of the
      genome in active and paused transcriptional states (~48% each), with ~4%
      definitively silenced (neither initiation nor elongation). Differentiation to
      mesoderm changed the transcriptional state of 12% of the genome, with roughly
      equal numbers of genes moving toward activation or silencing. Interestingly,
      almost all loci (98-99%) changing transcriptional state do so either by entering
      or exiting the paused state. A majority of these transitions involve either loss
      of initiation, as genes specifying alternate lineages are archived, or gain of
      initiation, in anticipation of future full-length expression. The addition of
      chromatin dynamics permitted much earlier predictions of final cell fate compared
      to sole use of conventional transcript arrays. These findings indicate that the
      paused state may be the major transition state for genes changing expression
      during differentiation, and implicate control of transcriptional elongation as a
      key checkpoint in lineage specification.

PMID- 21886767
TI  - Early adaptive humoral immune responses and virus clearance in humans recently
      infected with pandemic 2009 H1N1 influenza virus.
AB  - Few studies on the humoral immune responses in human during natural influenza
      infection have been reported. Here, we used serum samples from pandemic 2009 H1N1
      influenza infected patients to characterize the humoral immune responses to
      influenza during natural infection in humans. We observed for the first time that
      the pandemic 2009 H1N1 influenza induced influenza A-specific IgM within days
      after symptoms onset, whereas the unit of IgG did not changed. The magnitude of
      influenza A-specific IgM antibodies might have a value in predicting the rate of
      virus clearance to some degree. However, the newly developed IgM was not
      associated with hemagglutination inhibition (HI) activities in the same samples
      but correlated with HI activities of subsequently collected sera which were
      mediated by IgG antibodies, indicating that IgM was critical for influenza
      infection and influences subsequent IgG antibody responses. These findings
      provide new important insights on the human immunity to natural influenza
      infection.

PMID- 21886768
TI  - B cell depletion in HIV-1 subtype A infected Ugandan adults: relationship to CD4
      T cell count, viral load and humoral immune responses.
AB  - To better understand the nature of B cell dysfunctions in subjects infected with
      HIV-1 subtype A, a rural cohort of 50 treatment-naive Ugandan patients
      chronically infected with HIV-1 subtype A was studied, and the relationship
      between B cell depletion and HIV disease was assessed. B cell absolute counts
      were found to be significantly lower in HIV-1+ patients, when compared to
      community matched negative controls (p<0.0001). HIV-1-infected patients displayed
      variable functional and binding antibody titers that showed no correlation with
      viral load or CD4+ T cell count. However, B cell absolute counts were found to
      correlate inversely with neutralizing antibody (NAb) titers against subtype A (p
      = 0.05) and subtype CRF02_AG (p = 0.02) viruses. A positive correlation was
      observed between subtype A gp120 binding antibody titers and NAb breadth (p =
      0.02) and mean titer against the 10 viruses (p = 0.0002). In addition, HIV-1
      subtype A sera showed preferential neutralization of the 5 subtype A or CRF02_AG
      pseudoviruses, as compared with 5 pseudoviruses from subtypes B, C or D
      (p<0.001). These data demonstrate that in patients with chronic HIV-1 subtype A
      infection, significant B cell depletion can be observed, the degree of which does
      not appear to be associated with a decrease in functional antibodies. These
      findings also highlight the potential importance of subtype in the specificity of
      cross-clade neutralization in HIV-1 infection.

PMID- 21886769
TI  - Characterisation and carriage ratio of Clostridium difficile strains isolated
      from a community-dwelling elderly population in the United Kingdom.
AB  - BACKGROUND: Community-associated Clostridium difficile infection (CDI) appears to
      be an increasing problem. Reported carriage rates by C. difficile are debatable
      with suggestions that primary asymptomatic carriage is associated with decreased
      risk of subsequent diarrhoea. However, knowledge of potential reservoirs and
      intestinal carriage rates in the community, particularly in the elderly, the most
      susceptible group, is limited. We have determined the presence of C. difficile in
      the faeces of a healthy elderly cohort living outside of long-term care
      facilities (LCFs) in the United Kingdom. METHODS: Faecal samples from 149
      community-based healthy elderly volunteers (median age 81 years) were screened
      for C. difficile using direct (Brazier's CCEY) and enrichment (Cooked Meat broth)
      culture methods and a glutamate dehydrogenase (GDH) immunoassay. Isolates were
      PCR-ribotyped and analysed for toxin production and the presence of toxin genes.
      RESULTS: Of 149 faecal samples submitted, six (4%) were found to contain C.
      difficile. One particular sample was positive by both the GDH immunoassay and
      direct culture, and concurrently produced two distinct strain types: one
      toxigenic and the other non-toxigenic. The other five samples were only positive
      by enrichment culture method. Overall, four C. difficile isolates were non
      toxigenic (PCR-ribotypes 009, 026 (n = 2) and 039), while three were toxigenic
      (PCR-ribotypes 003, 005 and 106). All individuals who had a positive culture were
      symptom-free and none of them had a history of CDI and/or antibiotics use in the
      3 month period preceding recruitment. CONCLUSIONS: To our knowledge, this is the
      first study of the presence of C. difficile in healthy elderly community-dwelling
      individuals residing outside of LCFs. The observed carriage rate is lower than
      that reported for individuals in LCFs and interestingly no individual carried the
      common epidemic strain PCR-ribotype 027 (NAP1/BI). Further follow-up of
      asymptomatic carriers in the community, is required to evaluate host
      susceptibility to CDI and identify dynamic changes in the host and microbial
      environment that are associated with pathogenicity.

PMID- 21886770
TI  - Temporal associations between daytime physical activity and sleep in children.
AB  - OBJECTIVES: We examined temporal associations between objectively-measured
      physical activity (PA) during the day and in the evening, and sleep quantity and
      quality. STUDY DESIGN: PA and sleep were measured by actigraphs for an average of
      one week in an epidemiological cohort study of 275 eight-year-old children.
      RESULTS: For each one standard deviation (SD) unit of increased PA during the
      day, sleep duration was decreased by 0.30, sleep efficiency by 0.16, and sleep
      fragmentation increased by 0.08 SD units that night. For each one SD unit
      increase in sleep duration and efficiency the preceding night, PA the following
      day decreased by 0.09 and 0.16 SD units, respectively. When we contrasted days
      with a high amount of moderate to vigorous activity during the day or in the
      evening to days with a more sedentary profile, the results were essentially
      similar. However, moderate to vigorous PA in the evening shortened sleep latency.
      CONCLUSIONS: The relationship between a higher level of PA and poorer sleep is
      bidirectional. These within-person findings challenge epidemiological findings
      showing that more active people report better sleep. Since only a few studies
      using objective measurements of both PA and sleep have been conducted in
      children, further studies are needed to confirm/refute these results.

PMID- 21886771
TI  - Protein diffusion in mammalian cell cytoplasm.
AB  - We introduce a new method for mesoscopic modeling of protein diffusion in an
      entire cell. This method is based on the construction of a three-dimensional
      digital model cell from confocal microscopy data. The model cell is segmented
      into the cytoplasm, nucleus, plasma membrane, and nuclear envelope, in which
      environment protein motion is modeled by fully numerical mesoscopic methods.
      Finer cellular structures that cannot be resolved with the imaging technique,
      which significantly affect protein motion, are accounted for in this method by
      assigning an effective, position-dependent porosity to the cell. This porosity
      can also be determined by confocal microscopy using the equilibrium distribution
      of a non-binding fluorescent protein. Distinction can now be made within this
      method between diffusion in the liquid phase of the cell (cytosol/nucleosol) and
      the cytoplasm/nucleoplasm. Here we applied the method to analyze fluorescence
      recovery after photobleach (FRAP) experiments in which the diffusion coefficient
      of a freely-diffusing model protein was determined for two different cell lines,
      and to explain the clear difference typically observed between conventional FRAP
      results and those of fluorescence correlation spectroscopy (FCS). A large
      difference was found in the FRAP experiments between diffusion in the
      cytoplasm/nucleoplasm and in the cytosol/nucleosol, for all of which the
      diffusion coefficients were determined. The cytosol results were found to be in
      very good agreement with those by FCS.

PMID- 21886772
TI  - Fukutin-related protein resides in the Golgi cisternae of skeletal muscle fibres
      and forms disulfide-linked homodimers via an N-terminal interaction.
AB  - Limb-Girdle Muscular Dystrophy type 2I (LGMD2I) is an inheritable autosomal,
      recessive disorder caused by mutations in the FuKutin-Related Protein (FKRP) gene
      (FKRP) located on chromosome 19 (19q13.3). Mutations in FKRP are also associated
      with Congenital Muscular Dystrophy (MDC1C), Walker-Warburg Syndrome (WWS) and
      Muscle Eye Brain disease (MEB). These four disorders share in common an
      incomplete/aberrant O-glycosylation of the membrane/extracellular matrix (ECM)
      protein alpha-dystroglycan. However, further knowledge on the FKRP structure and
      biological function is lacking, and its intracellular location is controversial.
      Based on immunogold electron microscopy of human skeletal muscle sections we
      demonstrate that FKRP co-localises with the middle-to-trans-Golgi marker MG160,
      between the myofibrils in human rectus femoris muscle fibres. Chemical cross
      linking experiments followed by pairwise yeast 2-hybrid experiments, and co
      immune precipitation, demonstrate that FKRP can exist as homodimers as well as in
      large multimeric protein complexes when expressed in cell culture. The FKRP
      homodimer is kept together by a disulfide bridge provided by the most N-terminal
      cysteine, Cys6. FKRP contains N-glycan of high mannose and/or hybrid type;
      however, FKRP N-glycosylation is not required for FKRP homodimer or multimer
      formation. We propose a model for FKRP which is consistent with that of a Golgi
      resident type II transmembrane protein.

PMID- 21886773
TI  - HIV-1 Nef induces proinflammatory state in macrophages through its acidic cluster
      domain: involvement of TNF alpha receptor associated factor 2.
AB  - BACKGROUND: HIV-1 Nef is a virulence factor that plays multiple roles during HIV
      replication. Recently, it has been described that Nef intersects the CD40
      signalling in macrophages, leading to modification in the pattern of secreted
      factors that appear able to recruit, activate and render T lymphocytes
      susceptible to HIV infection. The engagement of CD40 by CD40L induces the
      activation of different signalling cascades that require the recruitment of
      specific tumor necrosis factor receptor-associated factors (i.e. TRAFs). We
      hypothesized that TRAFs might be involved in the rapid activation of NF-kappaB,
      MAPKs and IRF-3 that were previously described in Nef-treated macrophages to
      induce the synthesis and secretion of proinflammatory cytokines, chemokines and
      IFNbeta to activate STAT1, -2 and -3. METHODOLOGY/PRINCIPAL FINDINGS: Searching
      for possible TRAF binding sites on Nef, we found a TRAF2 consensus binding site
      in the AQEEEE sequence encompassing the conserved four-glutamate acidic cluster.
      Here we show that all the signalling effects we observed in Nef treated
      macrophages depend on the integrity of the acidic cluster. In addition, Nef was
      able to interact in vitro with TRAF2, but not TRAF6, and this interaction
      involved the acidic cluster. Finally silencing experiments in THP-1 monocytic
      cells indicate that both TRAF2 and, surprisingly, TRAF6 are required for the Nef
      induced tyrosine phosphorylation of STAT1 and STAT2. CONCLUSIONS: Results
      reported here revealed TRAF2 as a new possible cellular interactor of Nef and
      highlighted that in monocytes/macrophages this viral protein is able to
      manipulate both the TRAF/NF-kappaB and TRAF/IRF-3 signalling axes, thereby
      inducing the synthesis of proinflammatory cytokines and chemokines as well as
      IFNbeta.

PMID- 21886774
TI  - Phenothiourea sensitizes zebrafish cranial neural crest and extraocular muscle
      development to changes in retinoic acid and IGF signaling.
AB  - 1-Phenyl 2-thiourea (PTU) is a tyrosinase inhibitor commonly used to block
      pigmentation and aid visualization of zebrafish development. At the standard
      concentration of 0.003% (200 uM), PTU inhibits melanogenesis and reportedly has
      minimal other effects on zebrafish embryogenesis. We found that 0.003% PTU
      altered retinoic acid and insulin-like growth factor (IGF) regulation of neural
      crest and mesodermal components of craniofacial development. Reduction of
      retinoic acid synthesis by the pan-aldehyde dehydrogenase inhibitor
      diethylbenzaldehyde, only when combined with 0.003% PTU, resulted in extraocular
      muscle disorganization. PTU also decreased retinoic acid-induced teratogenic
      effects on pharyngeal arch and jaw cartilage despite morphologically normal
      appearing PTU-treated controls. Furthermore, 0.003% PTU in combination with
      inhibition of IGF signaling through either morpholino knockdown or pharmacologic
      inhibition of tyrosine kinase receptor phosphorylation, disrupted jaw development
      and extraocular muscle organization. PTU in and of itself inhibited neural crest
      development at higher concentrations (0.03%) and had the greatest inhibitory
      effect when added prior to 22 hours post fertilization (hpf). Addition of 0.003%
      PTU between 4 and 20 hpf decreased thyroxine (T4) in thyroid follicles in the
      nasopharynx of 96 hpf embryos. Treatment with exogenous triiodothyronine (T3) and
      T4 improved, but did not completely rescue, PTU-induced neural crest defects.
      Thus, PTU should be used with caution when studying zebrafish embryogenesis as it
      alters the threshold of different signaling pathways important during
      craniofacial development. The effects of PTU on neural crest development are
      partially caused by thyroid hormone signaling.

PMID- 21886775
TI  - Mannosidase 2, alpha 1 deficiency is associated with ricin resistance in
      embryonic stem (ES) cells.
AB  - Host gene products required for mediating the action of toxins are potential
      targets for reversing or controlling their pathogenic impact following exposure.
      To identify such targets libraries of insertional gene-trap mutations generated
      with a PiggyBac transposon in Blm-deficient embryonic stem cells were exposed to
      the plant toxin, ricin. Resistant clones were isolated and genetically
      characterised and one was found to be a homozygous mutant of the mannosidase 2,
      alpha 1 (Man2alpha1) locus with a matching defect in the homologous allele. The
      causality of the molecular lesion was confirmed by removal of the transposon
      following expression of PB-transposase. Comparative glycomic and lectin binding
      analysis of the Man2alpha1 (-/-) ricin resistant cells revealed an increase in
      the levels of hybrid glycan structures and a reduction in terminal beta-galactose
      moieties, potential target receptors for ricin. Furthermore, naive ES cells
      treated with inhibitors of the N-linked glycosylation pathway at the mannosidase
      2, alpha 1 step exhibited either full or partial resistance to ricin. Therefore,
      we conclusively identified mannosidase 2, alpha 1 deficiency to be associated
      with ricin resistance.

PMID- 21886776
TI  - The depolarizing action of GABA in cultured hippocampal neurons is not due to the
      absence of ketone bodies.
AB  - Two recent reports propose that the depolarizing action of GABA in the immature
      brain is an artifact of in vitro preparations in which glucose is the only energy
      source. The authors argue that this does not mimic the physiological environment
      because the suckling rats use ketone bodies and pyruvate as major sources of
      metabolic energy. Here, we show that availability of physiologically relevant
      levels of ketone bodies has no impact on the excitatory action of GABA in
      immature cultured hippocampal neurons. Addition of beta-hydroxybutyrate (BHB),
      the primary ketone body in the neonate rat, affected neither intracellular
      calcium elevation nor membrane depolarizations induced by the GABA-A receptor
      agonist muscimol, when assessed with calcium imaging or perforated patch-clamp
      recording, respectively. These results confirm that the addition of ketone bodies
      to the extracellular environment to mimic conditions in the neonatal brain does
      not reverse the chloride gradient and therefore render GABA hyperpolarizing. Our
      data are consistent with the existence of a genuine "developmental switch"
      mechanism in which GABA goes from having a predominantly excitatory role in
      immature cells to a predominantly inhibitory one in adults.

PMID- 21886777
TI  - Cochlin induced TREK-1 co-expression and annexin A2 secretion: role in trabecular
      meshwork cell elongation and motility.
AB  - Fluid flow through large interstitial spaces is sensed at the cellular level, and
      mechanistic responses to flow changes enables expansion or contraction of the
      cells modulating the surrounding area and brings about changes in fluid flow. In
      the anterior eye chamber, aqueous humor, a clear fluid, flows through trabecular
      meshwork (TM), a filter like region. Cochlin, a secreted protein in the
      extracellular matrix, was identified in the TM of glaucomatous patients but not
      controls by mass spectrometry. Cochlin undergoes shear induced multimerization
      and plays a role in mechanosensing of fluid shear. Cytoskeletal changes in
      response to mechanosensing in the ECM by cochlin will necessitate transduction of
      mechanosensing. TREK-1, a stretch activated outward rectifying potassium channel
      protein known to act as mechanotransducer was found to be expressed in TM.
      Cochlin expression results in co-expression of TREK-1 and filopodia formation.
      Prolonged cochlin expression results in expression and subsequent secretion of
      annexin A2, a protein known to play a role in cytoskeletal remodeling. Cochlin
      interacts with TREK-1 and annexin A2. Cochlin-TREK-1 interaction has functional
      consequences and results in changes in cell shape and motility. Annexin A2
      expression and secretion follows cochlin-TREK-1 syn-expression and correlates
      with cell elongation. Thus cytoskeleton changes in response to fluid shear sensed
      by cochlin are further mediated by TREK-1 and annexin A2.

PMID- 21886778
TI  - Treatment of tuberculosis in a region with high drug resistance: outcomes, drug
      resistance amplification and re-infection.
AB  - INTRODUCTION: Emerging antituberculosis drug resistance is a serious threat for
      tuberculosis (TB) control, especially in Eastern European countries. METHODS: We
      combined drug susceptibility results and molecular strain typing data with
      treatment outcome reports to assess the influence of drug resistance on TB
      treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia).
      Patients received individualized treatment regimens based on drug susceptibility
      testing (DST) results. Definitions for antituberculosis drug resistance and
      treatment outcomes were in line with current WHO recommendations. First and
      second line DST, and molecular typing were performed in a supranational
      laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum
      smear-positive TB patients at baseline and during treatment. RESULTS: At
      baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients.
      Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were
      found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB
      strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%)
      fully susceptible patients at baseline were re-infected with a MDR-TB strain and
      2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/47
      (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was
      observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with
      fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin
      resistance was significantly associated with a negative treatment outcome.
      CONCLUSION: In Abkhazia, a region with high prevalence of drug resistant TB, the
      use of individualized MDR-TB treatment regimens resulted in poor treatment
      outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes
      the importance of infection control in hospitals.

PMID- 21886779
TI  - HIV drug resistance (HIVDR) in antiretroviral therapy-naive patients in Tanzania
      not eligible for WHO threshold HIVDR survey is dramatically high.
AB  - BACKGROUND: The World Health Organization (WHO) has recommended guidelines for a
      HIV drug resistance (HIVDR) survey for resource-limited countries. Eligibility
      criteria for patients include age below 25 years in order to focus on the
      prevalence of transmitted HIVDR (tHIVDR) in newly-infected individuals. Most of
      the participating sites across Africa have so far reported tHIVDR prevalences of
      below 5%. In this study we investigated whether the rate of HIVDR in patients <25
      years is representative for HIVDR in the rest of the therapy-naive population.
      METHODS AND FINDINGS: HIVDR was determined in 88 sequentially enrolled ART-naive
      patients from Mwanza, Tanzania (mean age 35.4 years). Twenty patients were aged
      <25 years and 68 patients were aged 25-63 years. The frequency of HIVDR in the
      study population was 14.8% (95%; CI 0.072-0.223) and independent of NVP
      resistance induced by prevention of mother-to-child transmission programs.
      Patients >25 years had a significantly higher HIVDR frequency than younger
      patients (19.1%; 95% CI 0.095-0.28) versus 0%, P = 0.0344). In 2 out of the 16
      patients with HIVDR we found traces of antiretrovirals (ARVs) in plasma.
      CONCLUSIONS: ART-naive patients aged over 25 years exhibited significantly higher
      HIVDR than younger patients. Detection of traces of ARVs in individuals with
      HIVDR suggests that besides transmission, undisclosed misuse of ARVs may
      constitute a significant factor in the generation of the observed high HIVDR
      rate. The current WHO tHIVDR survey that is solely focused on the transmission of
      HIVDR and that excludes patients over 25 years of age may therefore result in
      substantial underestimation of the prevalence of HIVDR in the therapy-naive
      population. Similar studies should be performed also in other areas to test
      whether the so far reported optimistic picture of low HIVDR prevalence in young
      individuals is really representative for the rest of the ART-naive HIV-infected
      population.

PMID- 21886780
TI  - Hepcidin levels and their determinants in different types of myelodysplastic
      syndromes.
AB  - Iron overload may represent an additional clinical problem in patients with
      Myelodysplastic Syndromes (MDS), with recent data suggesting prognostic
      implications. Beyond red blood cells transfusions, dysregulation of hepcidin, the
      key iron hormone, may play a role, but studies until now have been hampered by
      technical problems. Using a recently validated assay, we measured serum hepcidin
      in 113 patients with different MDS subtypes. Mean hepcidin levels were
      consistently heterogeneous across different MDS subtypes, with the lowest levels
      in refractory anemia with ringed sideroblasts (RARS, 1.43 nM) and the highest in
      refractory anemia with excess blasts (RAEB, 11.3 nM) or in chronic myelomonocytic
      leukemia (CMML, 10.04 nM) (P = 0.003 by ANOVA). MDS subtypes remained significant
      predictors of hepcidin in multivariate analyses adjusted for ferritin and
      transfusion history. Consistently with current knowledge on hepcidin
      action/regulation, RARS patients had the highest levels of toxic non-transferrin
      bound-iron, while RAEB and CMML patients had substantial elevation of C-Reactive
      Protein as compared to other MDS subtypes, and showed lost of homeostatic
      regulation by iron. Growth differentiation factor 15 did not appear as a primary
      hepcidin regulator in this series. If confirmed, these results may help to
      calibrate future treatments with chelating agents and/or hepcidin modulators in
      MDS patients.

PMID- 21886781
TI  - Working memory training using mental calculation impacts regional gray matter of
      the frontal and parietal regions.
AB  - Training working memory (WM) improves performance on untrained cognitive tasks
      and alters functional activity. However, WM training's effects on gray matter
      morphology and a wide range of cognitive tasks are still unknown. We investigated
      this issue using voxel-based morphometry (VBM), various psychological measures,
      such as non-trained WM tasks and a creativity task, and intensive adaptive
      training of WM using mental calculations (IATWMMC), all of which are typical WM
      tasks. IATWMMC was associated with reduced regional gray matter volume in the
      bilateral fronto-parietal regions and the left superior temporal gyrus. It
      improved verbal letter span and complex arithmetic ability, but deteriorated
      creativity. These results confirm the training-induced plasticity in
      psychological mechanisms and the plasticity of gray matter structures in regions
      that have been assumed to be under strong genetic control.

PMID- 21886782
TI  - P38 mitogen-activated protein kinase inhibitor, FR167653, inhibits parathyroid
      hormone related protein-induced osteoclastogenesis and bone resorption.
AB  - p38 mitogen-activated protein kinase (MAPK) acts downstream in the signaling
      pathway that includes receptor activator of NF-kappaB (RANK), a powerful inducer
      of osteoclast formation and activation. We investigated the role of p38 MAPK in
      parathyroid hormone related protein (PTHrP)-induced osteoclastogenesis in vitro
      and PTHrP-induced bone resorption in vivo. The ability of FR167653 to inhibit
      osteoclast formation was evaluated by counting the number of tartrate-resistant
      acid phosphatase positive multinucleated cells (TRAP-positive MNCs) in in vitro
      osteoclastgenesis assays. Its mechanisms were evaluated by detecting the
      expression level of c-Fos and nuclear factor of activated T cells c1 (NFATc1) in
      bone marrow macrophages (BMMs) stimulated with sRANKL and M-CSF, and by detecting
      the expression level of osteoprotegerin (OPG) and RANKL in bone marrow stromal
      cells stimulated with PTHrP in the presence of FR167653. The function of FR167653
      on bone resorption was assessed by measuring the bone resorption area
      radiographically and by counting osteoclast number per unit bone tissue area in
      calvaria in a mouse model of bone resorption by injecting PTHrP subcutaneously
      onto calvaria. Whole blood ionized calcium levels were also recorded. FR167653
      inhibited PTHrP-induced osteoclast formation and PTHrP-induced c-Fos and NFATc1
      expression in bone marrow macrophages, but not the expression levels of RANKL and
      OPG in primary bone marrow stromal cells treated by PTHrP. Furthermore, bone
      resorption area and osteoclast number in vivo were significantly decreased by the
      treatment of FR167653. Systemic hypercalcemia was also partially inhibited.
      Inhibition of p38 MAPK by FR167653 blocks PTHrP-induced osteoclastogenesis in
      vitro and PTHrP-induced bone resorption in vivo, suggesting that the p38 MAPK
      signaling pathway plays a fundamental role in PTHrP-induced osteoclastic bone
      resorption.

PMID- 21886783
TI  - The disequilibrium of nucleosomes distribution along chromosomes plays a
      functional and evolutionarily role in regulating gene expression.
AB  - To further understand the relationship between nucleosome-space occupancy (NO)
      and global transcriptional activity in mammals, we acquired a set of genome-wide
      nucleosome distribution and transcriptome data from the mouse cerebrum and testis
      based on ChIP (H3)-seq and RNA-seq, respectively. We identified a nearly
      consistent NO patterns among three mouse tissues--cerebrum, testis, and ESCs--and
      found, through clustering analysis for transcriptional activation, that the NO
      variations among chromosomes are closely associated with distinct expression
      levels between house-keeping (HK) genes and tissue-specific (TS) genes. Both TS
      and HK genes form clusters albeit the obvious majority. This feature implies that
      NO patterns, i.e. nucleosome binding and clustering, are coupled with gene
      clustering that may be functionally and evolutionarily conserved in regulating
      gene expression among different cell types.

PMID- 21886784
TI  - Ablation of TSC2 enhances insulin secretion by increasing the number of
      mitochondria through activation of mTORC1.
AB  - AIM: We previously found that chronic tuberous sclerosis protein 2 (TSC2)
      deletion induces activation of mammalian target of rapamycin Complex 1 (mTORC1)
      and leads to hypertrophy of pancreatic beta cells from pancreatic beta cell
      specific TSC2 knockout (betaTSC2(-/-)) mice. The present study examines the
      effects of TSC2 ablation on insulin secretion from pancreatic beta cells.
      METHODS: Isolated islets from betaTSC2(-/-) mice and TSC2 knockdown insulin 1
      (INS-1) insulinoma cells treated with small interfering ribonucleic acid were
      used to investigate insulin secretion, ATP content and the expression of
      mitochondrial genes. RESULTS: Activation of mTORC1 increased mitochondrial DNA
      expression, mitochondrial density and ATP production in pancreatic beta cells of
      betaTSC2(-/-) mice. In TSC2 knockdown INS-1 cells, mitochondrial DNA expression,
      mitochondrial density and ATP production were increased compared with those in
      control INS-1 cells, consistent with the phenotype of betaTSC2(-/-) mice. TSC2
      knockdown INS-1 cells also exhibited augmented insulin secretory response to
      glucose. Rapamycin inhibited mitochondrial DNA expression and ATP production as
      well as insulin secretion in response to glucose. Thus, betaTSC2(-/-) mice
      exhibit hyperinsulinemia due to an increase in the number of mitochondria as well
      as enlargement of individual beta cells via activation of mTORC1. CONCLUSION:
      Activation of mTORC1 by TSC2 ablation increases mitochondrial biogenesis and
      enhances insulin secretion from pancreatic beta cells.

PMID- 21886785
TI  - Comparative analysis of bacterial communities in a potato field as determined by
      pyrosequencing.
AB  - BACKGROUND: Plants selectively attract particular soil microorganisms, in
      particular consumers of root-excreted compounds. It is unclear to what extent
      cultivar type and/or growth stage affect this process. METHODOLOGY/PRINCIPAL
      FINDINGS: DNA-based pyrosequencing was used to characterize the structure of
      bacterial communities in a field cropped with potato. The rhizospheres of six
      cultivars denoted Aveka, Aventra, Karnico, Modena, Premiere and Desiree, at three
      growth stages (young, flowering and senescence) were examined, in addition to
      corresponding bulk soils. Around 350,000 sequences were obtained (5,700 to 38,000
      per sample). Across all samples, rank abundance distributions best fitted the
      power law model, which indicates a community composed of a few highly dominant
      species next to numerous rare species. Grouping of the sequences showed that
      members of the Actinobacteria, Alphaproteobacteria, next to as-yet-unclassified
      bacteria, dominated. Other groups that were consistently found, albeit at lower
      abundance, were Beta-, Gamma- and Deltaproteobacteria and Acidobacteria.
      Principal components analyses revealed that rhizosphere samples were
      significantly different from corresponding bulk soil in each growth stage.
      Furthermore, cultivar effects were found in the young plant stage, whereas these
      became insignificant in the flowering and senescence stages. Besides, an effect
      of time of season was observed for both rhizosphere and bulk soils. The analyzed
      rhizosphere samples of the potato cultivars were grouped into two groups, in
      accordance with the allocation of carbon to starch in their tubers, i.e. Aveka,
      Aventra and Karnico (high) versus Premiere and Desiree (low) and thus replicates
      per group were established. CONCLUSIONS: Across all potato cultivars, the young
      plant stages revealed cultivar-dependent bacterial community structures, which
      disappeared in the flowering and senescence stages. Furthermore, Pseudomonas,
      Beta-, Alpha- and Deltaproteobacteria flourished under different ecological
      conditions than the Acidobacteria.

PMID- 21886786
TI  - Monoclonal antibodies recognizing the non-tandem repeat regions of the human
      mucin MUC4 in pancreatic cancer.
AB  - The MUC4 mucin is a high molecular weight, membrane-bound, and highly
      glycosylated protein. It is a multi-domain protein that is putatively cleaved
      into a large mucin-like subunit (MUC4alpha) and a C-terminal growth-factor like
      subunit (MUC4beta). MUC4 plays critical roles in physiological and pathological
      conditions and is aberrantly overexpressed in several cancers, including those of
      the pancreas, cervix, breast and lung. It is also a potential biomarker for the
      diagnosis, prognosis and progression of several malignancies. Further, MUC4 plays
      diverse functional roles in cancer initiation and progression as evident from its
      involvement in oncogenic transformation, proliferation, inhibition of apoptosis,
      motility and invasion, and resistance to chemotherapy in human cancer cells. We
      have previously generated a monoclonal antibody 8G7, which is directed against
      the TR region of MUC4, and has been extensively used to study the expression of
      MUC4 in several malignancies. Here, we describe the generation of anti-MUC4
      antibodies directed against the non-TR regions of MUC4. Recombinant glutathione-S
      transferase (GST)-fused MUC4alpha fragments, both upstream (MUC4alpha-N-Ter) and
      downstream (MUC4alpha-C-Ter) of the TR domain, were used as immunogens to
      immunize BALB/c mice. Following cell fusion, hybridomas were screened using the
      aforementioned recombinant proteins ad lysates from human pancreatic cell lines.
      Three anti MUC4alpha-N-Ter and one anti-MUC4alpha-C-Ter antibodies were
      characterized by several inmmunoassays including enzyme-linked immunosorbent
      assay (ELISA), immunoblotting, immunofluorescene, flow cytometry and
      immunoprecipitation using MUC4 expressing human pancreatic cancer cell lines. The
      antibodies also reacted with the MUC4 in human pancreatic tumor sections in
      immunohistochemical analysis. The new domain-specific anti-MUC4 antibodies will
      serve as important reagents to study the structure-function relationship of MUC4
      domains and for the development of MUC4-based diagnostics and therapeutics.

PMID- 21886787
TI  - Identification of a highly conserved H1 subtype-specific epitope with diagnostic
      potential in the hemagglutinin protein of influenza A virus.
AB  - Subtype specificity of influenza A virus (IAV) is determined by its two surface
      glycoproteins, hemagglutinin (HA) and neuraminidase (NA). For HA, 16 distinct
      subtypes (H1-H16) exist, while nine exist for NA. The epidemic strains of H1N1
      IAV change frequently and cause annual seasonal epidemics as well as occasional
      pandemics, such as the notorious 1918 influenza pandemic. The recent introduction
      of pandemic A/H1N1 IAV (H1N1pdm virus) into humans re-emphasizes the public
      health concern about H1N1 IAV. Several studies have identified conserved epitopes
      within specific HA subtypes that can be used for diagnostics. However, immune
      specific epitopes in H1N1 IAV have not been completely assessed. In this study,
      linear epitopes on the H1N1pdm viral HA protein were identified by peptide
      scanning using libraries of overlapping peptides against convalescent sera from
      H1N1pdm patients. One epitope, P5 (aa 58-72) was found to be immunodominant in
      patients and to evoke high titer antibodies in mice. Multiple sequence alignments
      and in silico coverage analysis showed that this epitope is highly conserved in
      influenza H1 HA [with a coverage of 91.6% (9,860/10,767)] and almost completely
      absent in other subtypes [with a coverage of 3.3% (792/23,895)]. This previously
      unidentified linear epitope is located outside the five well-recognized antigenic
      sites in HA. A peptide ELISA method based on this epitope was developed and
      showed high correlation (chi(2) = 51.81, P<0.01, Pearson correlation coefficient
      R = 0.741) with a hemagglutination inhibition test. The highly conserved H1
      subtype-specific immunodominant epitope may form the basis for developing novel
      assays for sero-diagnosis and active surveillance against H1N1 IAVs.

PMID- 21886788
TI  - Lhx2 is required for patterning and expansion of a distinct progenitor cell
      population committed to eye development.
AB  - Progenitor cells committed to eye development become specified in the prospective
      forebrain and develop subsequently into the optic vesicle and the optic cup. The
      optic vesicle induces formation of the lens placode in surface ectoderm from
      which the lens develops. Numerous transcription factors are involved in this
      process, including the eye-field transcription factors. However, many of these
      transcription factors also regulate the patterning of the anterior neural plate
      and their specific role in eye development is difficult to discern since eye
      committed progenitor cells are poorly defined. By using a specific part of the
      Lhx2 promoter to regulate Cre recombinase expression in transgenic mice we have
      been able to define a distinct progenitor cell population in the forebrain solely
      committed to eye development. Conditional inactivation of Lhx2 in these
      progenitor cells causes an arrest in eye development at the stage when the optic
      vesicle induces lens placode formation in the surface ectoderm. The eye-committed
      progenitor cell population is present in the Lhx2(-/-) embryonic forebrain
      suggesting that commitment to eye development is Lhx2-independent. However, re
      expression of Lhx2 in Lhx2(-/-) progenitor cells only promotes development of
      retinal pigment epithelium cells, indicating that Lhx2 promotes the acquisition
      of the oligopotent fate of these progenitor cells. This approach also allowed us
      to identify genes that distinguish Lhx2 function in eye development from that in
      the forebrain. Thus, we have defined a distinct progenitor cell population in the
      forebrain committed to eye development and identified genes linked to Lhx2's
      function in the expansion and patterning of these progenitor cells.

PMID- 21886789
TI  - E4orf1: a novel ligand that improves glucose disposal in cell culture.
AB  - Reducing dietary fat intake and excess adiposity, the cornerstones of behavioral
      treatment of insulin resistance (IR), are marginally successful over the long
      term. Ad36, a human adenovirus, offers a template to improve IR, independent of
      dietary fat intake or adiposity. Ad36 increases cellular glucose uptake via a Ras
      mediated activation of phosphatidyl inositol 3-kinase(PI3K), and improves
      hyperglycemia in mice, despite a high-fat diet and without reducing adiposity. Ex
      vivo studies suggest that Ad36 improves hyperglycemia in mice by increasing
      glucose uptake by adipose tissue and skeletal muscle, and by reducing hepatic
      glucose output. It is impractical to use Ad36 for therapeutic action. Instead, we
      investigated if the E4orf1 protein of Ad36, mediates its anti-hyperglycemic
      action. Such a candidate protein may offer an attractive template for therapeutic
      development. Experiment-1 determined that Ad36 'requires' E4orf1 protein to up
      regulate cellular glucose uptake. Ad36 significantly increased glucose uptake in
      3T3-L1 preadipocytes, which was abrogated by knocking down E4orf1 with siRNA.
      Experiment-2 identified E4orf1 as 'sufficient' to up-regulate glucose uptake. 3T3
      L1 cells that inducibly express E4orf1, increased glucose uptake in an induction
      dependent manner, compared to null vector control cells. E4orf1 up-regulated PI3K
      pathway and increased abundance of Ras--the obligatory molecule in Ad36-induced
      glucose uptake. Experiment-3: Signaling studies of cells transiently transfected
      with E4orf1 or a null vector, revealed that E4orf1 may activate Ras/PI3K pathway
      by binding to Drosophila discs-large (Dlg1) protein. E4orf1 activated total Ras
      and, particularly the H-Ras isoform. By mutating the PDZ domain binding motif
      (PBM) of E4orf1, Experiment-4 showed that E4orf1 requires its PBM to increase Ras
      activation or glucose uptake. Experiment-5: In-vitro, a transient transfection by
      E4orf1 significantly increased glucose uptake in preadipocytes, adipocytes, or
      myoblasts, and reduced glucose output by hepatocytes. Thus, the highly attractive
      anti-hyperglycemic effect of Ad36 is mirrored by E4orf1 protein, which may offer
      a novel ligand to develop anti-hyperglycemic drugs.

PMID- 21886790
TI  - Rapid detection and subtyping of human influenza A viruses and reassortants by
      pyrosequencing.
AB  - BACKGROUND: Given the continuing co-circulation of the 2009 H1N1 pandemic
      influenza A viruses with seasonal H3N2 viruses, rapid and reliable detection of
      newly emerging influenza reassortant viruses is important to enhance our
      influenza surveillance. METHODOLOGY/PRINCIPAL FINDINGS: A novel pyrosequencing
      assay was developed for the rapid identification and subtyping of potential human
      influenza A virus reassortants based on all eight gene segments of the virus.
      Except for HA and NA genes, one universal set of primers was used to amplify and
      subtype each of the six internal genes. With this method, all eight gene segments
      of 57 laboratory isolates and 17 original specimens of seasonal H1N1, H3N2 and
      2009 H1N1 pandemic viruses were correctly matched with their corresponding
      subtypes. In addition, this method was shown to be capable of detecting
      reassortant viruses by correctly identifying the source of all 8 gene segments
      from three vaccine production reassortant viruses and three H1N2 viruses.
      CONCLUSIONS/SIGNIFICANCE: In summary, this pyrosequencing assay is a sensitive
      and specific procedure for screening large numbers of viruses for reassortment
      events amongst the commonly circulating human influenza A viruses, which is more
      rapid and cheaper than using conventional sequencing approaches.

PMID- 21886791
TI  - Area disease estimation based on sentinel hospital records.
AB  - BACKGROUND: Population health attributes (such as disease incidence and
      prevalence) are often estimated using sentinel hospital records, which are
      subject to multiple sources of uncertainty. When applied to these health
      attributes, commonly used biased estimation techniques can lead to false
      conclusions and ineffective disease intervention and control. Although some
      estimators can account for measurement error (in the form of white noise, usually
      after de-trending), most mainstream health statistics techniques cannot generate
      unbiased and minimum error variance estimates when the available data are biased.
      METHODS AND FINDINGS: A new technique, called the Biased Sample Hospital-based
      Area Disease Estimation (B-SHADE), is introduced that generates space-time
      population disease estimates using biased hospital records. The effectiveness of
      the technique is empirically evaluated in terms of hospital records of disease
      incidence (for hand-foot-mouth disease and fever syndrome cases) in Shanghai
      (China) during a two-year period. The B-SHADE technique uses a weighted summation
      of sentinel hospital records to derive unbiased and minimum error variance
      estimates of area incidence. The calculation of these weights is the outcome of a
      process that combines: the available space-time information; a rigorous
      assessment of both, the horizontal relationships between hospital records and the
      vertical links between each hospital's records and the overall disease situation
      in the region. In this way, the representativeness of the sentinel hospital
      records was improved, the possible biases of these records were corrected, and
      the generated area incidence estimates were best linear unbiased estimates
      (BLUE). Using the same hospital records, the performance of the B-SHADE technique
      was compared against two mainstream estimators. CONCLUSIONS: The B-SHADE
      technique involves a hospital network-based model that blends the optimal
      estimation features of the Block Kriging method and the sample bias correction
      efficiency of the ratio estimator method. In this way, B-SHADE can overcome the
      limitations of both methods: Block Kriging's inadequacy concerning the correction
      of sample bias and spatial clustering; and the ratio estimator's limitation as
      regards error minimization. The generality of the B-SHADE technique is further
      demonstrated by the fact that it reduces to Block Kriging in the case of unbiased
      samples; to ratio estimator if there is no correlation between hospitals; and to
      simple statistic if the hospital records are neither biased nor space-time
      correlated. In addition to the theoretical advantages of the B-SHADE technique
      over the two other methods above, two real world case studies (hand-foot-mouth
      disease and fever syndrome cases) demonstrated its empirical superiority, as
      well.

PMID- 21886792
TI  - Influenza and pneumonia mortality in 66 large cities in the United States in
      years surrounding the 1918 pandemic.
AB  - The 1918 influenza pandemic was a major epidemiological event of the twentieth
      century resulting in at least twenty million deaths worldwide; however, despite
      its historical, epidemiological, and biological relevance, it remains poorly
      understood. Here we examine the relationship between annual pneumonia and
      influenza death rates in the pre-pandemic (1910-17) and pandemic (1918-20)
      periods and the scaling of mortality with latitude, longitude and population
      size, using data from 66 large cities of the United States. The mean pre-pandemic
      pneumonia death rates were highly associated with pneumonia death rates during
      the pandemic period (Spearman rho = 0.64-0.72; P<0.001). By contrast, there was a
      weak correlation between pre-pandemic and pandemic influenza mortality rates.
      Pneumonia mortality rates partially explained influenza mortality rates in 1918
      (rho = 0.34, P = 0.005) but not during any other year. Pneumonia death counts
      followed a linear relationship with population size in all study years,
      suggesting that pneumonia death rates were homogeneous across the range of
      population sizes studied. By contrast, influenza death counts followed a power
      law relationship with a scaling exponent of ~0.81 (95%CI: 0.71, 0.91) in 1918,
      suggesting that smaller cities experienced worst outcomes during the pandemic. A
      linear relationship was observed for all other years. Our study suggests that
      mortality associated with the 1918-20 influenza pandemic was in part
      predetermined by pre-pandemic pneumonia death rates in 66 large US cities,
      perhaps through the impact of the physical and social structure of each city.
      Smaller cities suffered a disproportionately high per capita influenza mortality
      burden than larger ones in 1918, while city size did not affect pneumonia
      mortality rates in the pre-pandemic and pandemic periods.

PMID- 21886793
TI  - Intraspecific aflatoxin inhibition in Aspergillus flavus is thigmoregulated,
      independent of vegetative compatibility group and is strain dependent.
AB  - Biological control of preharvest aflatoxin contamination by atoxigenic stains of
      Aspergillus flavus has been demonstrated in several crops. The assumption is that
      some form of competition suppresses the fungus's ability to infect or produce
      aflatoxin when challenged. Intraspecific aflatoxin inhibition was demonstrated by
      others. This work investigates the mechanistic basis of that phenomenon. A
      toxigenic and atoxigenic isolate of A. flavus which exhibited intraspecific
      aflatoxin inhibition when grown together in suspended disc culture were not
      inhibited when grown in a filter insert-plate well system separated by a .4 or 3
      um membrane. Toxigenic and atoxigenic conidial mixtures (50?50) placed on both
      sides of these filters restored inhibition. There was ~50% inhibition when a 12
      um pore size filter was used. Conidial and mycelial diameters were in the 3.5-7.0
      um range and could pass through the 12 um filter. Larger pore sizes in the
      initially separated system restored aflatoxin inhibition. This suggests isolates
      must come into physical contact with one another. This negates a role for
      nutrient competition or for soluble diffusible signals or antibiotics in
      aflatoxin inhibition. The toxigenic isolate was maximally sensitive to inhibition
      during the first 24 hrs of growth while the atoxigenic isolate was always
      inhibition competent. The atoxigenic isolate when grown with a green fluorescent
      protein (GFP) toxigenic isolate failed to inhibit aflatoxin indicating that there
      is specificity in the touch inhibiton. Several atoxigenic isolates were found
      which inhibited the GFP isolate. These results suggest that an unknown signaling
      pathway is initiated in the toxigenic isolate by physical interaction with an
      appropriate atoxigenic isolate in the first 24 hrs which prevents or down
      regulates normal expression of aflatoxin after 3-5 days growth. We suspect thigmo
      downregulation of aflatoxin synthesis is the mechanistic basis of intraspecific
      aflatoxin inhibition and the major contributor to biological control of aflatoxin
      contamination.

PMID- 21886794
TI  - Knockdown of dystrophin Dp71 impairs PC12 cells cycle: localization in the
      spindle and cytokinesis structures implies a role for Dp71 in cell division.
AB  - The function of dystrophin Dp71 in neuronal cells remains to be established.
      Previously, we revealed the involvement of this protein in both nerve growth
      factor (NGF)-induced neuronal differentiation and cell adhesion by isolation and
      characterization of PC12 neuronal cells with depleted levels of Dp71. In this
      work, a novel phenotype of Dp71-knockdown cells was characterized, which is their
      delayed growth rate. Cell cycle analyses revealed an altered behavior of Dp71
      depleted cells, which consists of a delay in G0/G1 transition and an increase in
      apoptosis during nocodazole-induced mitotic arrest. Dp71 associates with lamin B1
      and beta-dystroglycan, proteins involved in aspects of the cell division cycle;
      therefore, we compared the distribution of Dp71 with that of lamin B1 and beta
      dystroglycan in PC12 cells at mitosis and cytokinesis by means of
      immunofluorescence and confocal microscopy analysis. All of these three proteins
      exhibited a similar immunostaining pattern, localized at mitotic spindle,
      cleavage furrow, and midbody. It is noteworthy that a drastic decreased staining
      in mitotic spindle, cleavage furrow, and midbody was observed for both lamin B1
      and beta-dystroglycan in Dp71-depleted cells. Furthermore, we demonstrated the
      interaction of Dp71 with lamin B1 in PC12 cells by immunoprecipitation and pull
      down assays, and importantly, we revealed that knockdown of Dp71 expression
      caused a marked reduction in lamin B1 levels and altered localization of the
      nuclear envelope protein emerin. Our data indicate that Dp71 is a component of
      the mitotic spindle and cytokinesis multi-protein apparatuses that might modulate
      the cell division cycle by affecting lamin B1 and beta-dystroglycan levels.

PMID- 21886795
TI  - Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation.
AB  - The early use of fresh frozen plasma as a resuscitative agent after hemorrhagic
      shock has been associated with improved survival, but the mechanism of protection
      is unknown. Hemorrhagic shock causes endothelial cell dysfunction and we
      hypothesized that fresh frozen plasma would restore endothelial integrity and
      reduce syndecan-1 shedding after hemorrhagic shock. A prospective, observational
      study in severely injured patients in hemorrhagic shock demonstrated
      significantly elevated levels of syndecan-1 (554+/-93 ng/ml) after injury, which
      decreased with resuscitation (187+/-36 ng/ml) but was elevated compared to normal
      donors (27+/-1 ng/ml). Three pro-inflammatory cytokines, interferon-gamma,
      fractalkine, and interleukin-1beta, negatively correlated while one anti
      inflammatory cytokine, IL-10, positively correlated with shed syndecan-1. These
      cytokines all play an important role in maintaining endothelial integrity. An in
      vitro model of endothelial injury then specifically examined endothelial
      permeability after treatment with fresh frozen plasma orlactated Ringers. Shock
      or endothelial injury disrupted junctional integrity and increased permeability,
      which was improved with fresh frozen plasma, but not lactated Ringers. Changes in
      endothelial cell permeability correlated with syndecan-1 shedding. These data
      suggest that plasma based resuscitation preserved endothelial syndecan-1 and
      maintained endothelial integrity, and may help to explain the protective effects
      of fresh frozen plasma after hemorrhagic shock.

PMID- 21886796
TI  - High density lipoprotein (HDL) promotes glucose uptake in adipocytes and glycogen
      synthesis in muscle cells.
AB  - BACKGROUND: High density lipoprotein (HDL) was reported to decrease plasma
      glucose and promote insulin secretion in type 2 diabetes patients. This
      investigation was designed to determine the effects and mechanisms of HDL on
      glucose uptake in adipocytes and glycogen synthesis in muscle cells. METHODS AND
      RESULTS: Actions of HDL on glucose uptake and GLUT4 translocation were assessed
      with 1-[(3)H]-2-deoxyglucose and plasma membrane lawn, respectively, in 3T3-L1
      adipocytes. Glycogen analysis was performed with amyloglucosidase and glucose
      oxidase-peroxidase methods in normal and palmitate-treated L6 cells. Small
      interfering RNA was used to observe role of scavenger receptor type I (SR-BI) in
      glucose uptake of HDL. Corresponding signaling molecules were detected by
      immunoblotting. HDL stimulated glucose uptake in a time- and concentration
      dependent manner in 3T3-L1 adipocytes. GLUT4 translocation was significantly
      increased by HDL. Glycogen deposition got enhanced in L6 muscle cells paralleling
      with elevated glycogen synthase kinase3 (GSK3) phosphorylation. Meanwhile,
      increased phosphorylations of Akt-Ser473 and AMP activated protein kinase (AMPK)
      alpha were detected in 3T3-L1 adipocytes. Glucose uptake and Akt-Ser473
      activation but not AMPK-alpha were diminished in SR-BI knock-down 3T3-L1 cells.
      CONCLUSIONS: HDL stimulates glucose uptake in 3T3-L1 adipocytes through enhancing
      GLUT4 translocation by mechanisms involving PI3K/Akt via SR-BI and AMPK signaling
      pathways, and increases glycogen deposition in L6 muscle cells through promoting
      GSK3 phosphorylation.

PMID- 21886797
TI  - Functional insight into the C-terminal extension of halolysin SptA from
      haloarchaeon Natrinema sp. J7.
AB  - Halolysin SptA from haloarchaeon Natrinema sp. J7 consists of a subtilisin-like
      catalytic domain and a C-terminal extension (CTE) containing two cysteine
      residues. In this report, we have investigated the function of the CTE using
      recombinant enzymes expressed in Haloferax volcanii WFD11. Deletion of the CTE
      greatly reduced but did not abolish protease activity, which suggests that the
      CTE is not essential for enzyme folding. Mutational analysis suggests that
      residues Cys303 and Cys338 within the CTE form a disulfide bond that make this
      domain resistant to autocleavage and proteolysis under hypotonic conditions.
      Characterization of full-length and CTE-truncation enzymes indicates the CTE not
      only confers extra stability to the enzyme but also assists enzyme activity on
      protein substrates by facilitating binding at high salinities. Interestingly,
      homology modeling of the CTE yields a beta-jelly roll-like structure similar to
      those seen in Claudin-binding domain of Clostridium perfringens enterotoxin
      (clostridial C-CPE) and collagen binding domain (CBD), and the CTE also possesses
      collagen-binding activity, making it a potential candidate as an anchoring unit
      in drug delivery systems.

PMID- 21886798
TI  - Opiate sensitization induces FosB/DeltaFosB expression in prefrontal cortical,
      striatal and amygdala brain regions.
AB  - Sensitization to the effects of drugs of abuse and associated stimuli contributes
      to drug craving, compulsive drug use, and relapse in addiction. Repeated opiate
      exposure produces behavioral sensitization that is hypothesized to result from
      neural plasticity in specific limbic, striatal and cortical systems. DeltaFosB
      and FosB are members of the Fos family of transcription factors that are
      implicated in neural plasticity in addiction. This study examined the effects of
      intermittent morphine treatment, associated with motor sensitization, on
      FosB/DeltaFosB levels using quantitative immunohistochemistry. Motor
      sensitization was tested in C57BL/6 mice that received six intermittent pre
      treatments (on days 1, 3, 5, 8, 10, 12) with either subcutaneous morphine (10
      mg/kg) or saline followed by a challenge injection of morphine or saline on day
      16. Mice receiving repeated morphine injections demonstrated significant
      increases in locomotor activity on days 8, 10, and 12 of treatment (vs. day 1),
      consistent with development of locomotor sensitization. A morphine challenge on
      day 16 significantly increased locomotor activity of saline pre-treated mice and
      produced even larger increases in motor activity in the morphine pre-treated
      mice, consistent with the expression of opiate sensitization. Intermittent
      morphine pre-treatment on these six pre-treatment days produced a significant
      induction of FosB/DeltaFosB, measured on day 16, in multiple brain regions
      including prelimbic (PL) and infralimbic (IL) cortex, nucleus accumbens (NAc)
      core, dorsomedial caudate-putamen (CPU), basolateral amygdala (BLA) and central
      nucleus of the amygdala (CNA) but not in a motor cortex control region. Opiate
      induced sensitization may develop via Fos/DeltaFosB plasticity in motivational
      pathways (NAc), motor outputs (CPU), and associative learning (PL, IL, BLA) and
      stress pathways (CNA).

PMID- 21886799
TI  - Can interactions between timing of vaccine-altered influenza pandemic waves and
      seasonality in influenza complications lead to more severe outcomes?
AB  - Vaccination can delay the peak of a pandemic influenza wave by reducing the
      number of individuals initially susceptible to influenza infection. Emerging
      evidence indicates that susceptibility to severe secondary bacterial infections
      following a primary influenza infection may vary seasonally, with peak
      susceptibility occurring in winter. Taken together, these two observations
      suggest that vaccinating to prevent a fall pandemic wave might delay it long
      enough to inadvertently increase influenza infections in winter, when primary
      influenza infection is more likely to cause severe outcomes. This could
      potentially cause a net increase in severe outcomes. Most pandemic models
      implicitly assume that the probability of severe outcomes does not vary
      seasonally and hence cannot capture this effect. Here we show that the
      probability of intensive care unit (ICU) admission per influenza infection in the
      2009 H1N1 pandemic followed a seasonal pattern. We combine this with an influenza
      transmission model to investigate conditions under which a vaccination program
      could inadvertently shift influenza susceptibility to months where the risk of
      ICU admission due to influenza is higher. We find that vaccination in advance of
      a fall pandemic wave can actually increase the number of ICU admissions in
      situations where antigenic drift is sufficiently rapid or where importation of a
      cross-reactive strain is possible. Moreover, this effect is stronger for
      vaccination programs that prevent more primary influenza infections. Sensitivity
      analysis indicates several mechanisms that may cause this effect. We also find
      that the predicted number of ICU admissions changes dramatically depending on
      whether the probability of ICU admission varies seasonally, or whether it is held
      constant. These results suggest that pandemic planning should explore the
      potential interactions between seasonally varying susceptibility to severe
      influenza outcomes and the timing of vaccine-altered pandemic influenza waves.

PMID- 21886800
TI  - Evaluating health workers' potential resistance to new interventions: a role for
      discrete choice experiments.
AB  - BACKGROUND: The currently recommended approach for preventing malaria in
      pregnancy (MiP), intermittent preventive treatment with sulphadoxine
      pyrimethamine (SP-IPT), has been questioned due to the spread of resistance to
      SP. Whilst trials are underway to test the efficacy of future alternative
      approaches, it is important to start exploring the feasibility of their
      implementation. METHODS AND FINDINGS: This study uses a discrete choice
      experiment (DCE) method to assess the potential resistance of health workers to
      changing strategies for control of MiP. In Ashanti region in Ghana, 133 antenatal
      clinic health workers were presented with 16 choice sets of two alternative
      policy options, each consisting of a bundle of six attributes representing
      certain clinical guidelines for controlling MiP (type of approach and drug used),
      possible associated maternal and neo-natal outcomes, workload and financial
      incentives. The data were analysed using a random effects logit model. Overall,
      staff showed a preference for a curative approach with pregnant women tested for
      malaria parasites and treated only if positive, compared to a preventive approach
      (OR 1.6; p = 0.001). Increasing the incidence of low birth weight or severe
      anaemia by 1% would reduce the odds of preferring an approach by 18% and 10%
      respectively. Midwives were more resistant to potential changes to current
      guidelines than lower-level cadres. CONCLUSIONS: In Ashanti Region, resistance to
      change by antenatal clinic workers from a policy of SP-IPT to IST would generally
      be low, and it would disappear amongst midwives if health outcomes for the mother
      and baby were improved by the new strategy. DCEs are a promising approach to
      identifying factors that will increase the likelihood of effective implementation
      of new interventions immediately after their efficacy has been proven.

PMID- 21886801
TI  - The neuronal transition probability (NTP) model for the dynamic progression of
      non-REM sleep EEG: the role of the suprachiasmatic nucleus.
AB  - Little attention has gone into linking to its neuronal substrates the dynamic
      structure of non-rapid-eye-movement (NREM) sleep, defined as the pattern of time
      course power in all frequency bands across an entire episode. Using the spectral
      power time-courses in the sleep electroencephalogram (EEG), we showed in the
      typical first episode, several moves towards-and-away from deep sleep, each
      having an identical pattern linking the major frequency bands beta, sigma and
      delta. The neuronal transition probability model (NTP)--in fitting the data well-
      successfully explained the pattern as resulting from stochastic transitions of
      the firing-rates of the thalamically-projecting brainstem-activating neurons,
      alternating between two steady dynamic-states (towards-and-away from deep sleep)
      each initiated by a so-far unidentified flip-flop. The aims here are to identify
      this flip-flop and to demonstrate that the model fits well all NREM episodes, not
      just the first. Using published data on suprachiasmatic nucleus (SCN) activity we
      show that the SCN has the information required to provide a threshold-triggered
      flip-flop for TIMING the towards-and-away alternations, information provided by
      sleep-relevant feedback to the SCN. NTP then determines the PATTERN of spectral
      power within each dynamic-state. NTP was fitted to individual NREM episodes 1-4,
      using data from 30 healthy subjects aged 20-30 years, and the quality of fit for
      each NREM measured. We show that the model fits well all NREM episodes and the
      best-fit probability-set is found to be effectively the same in fitting all
      subject data. The significant model-data agreement, the constant probability
      parameter and the proposed role of the SCN add considerable strength to the
      model. With it we link for the first time findings at cellular level and detailed
      time-course data at EEG level, to give a coherent picture of NREM dynamics over
      the entire night and over hierarchic brain levels all the way from the SCN to the
      EEG.

PMID- 21886802
TI  - Assessing Google flu trends performance in the United States during the 2009
      influenza virus A (H1N1) pandemic.
AB  - BACKGROUND: Google Flu Trends (GFT) uses anonymized, aggregated internet search
      activity to provide near-real time estimates of influenza activity. GFT estimates
      have shown a strong correlation with official influenza surveillance data. The
      2009 influenza virus A (H1N1) pandemic [pH1N1] provided the first opportunity to
      evaluate GFT during a non-seasonal influenza outbreak. In September 2009, an
      updated United States GFT model was developed using data from the beginning of
      pH1N1. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the accuracy of each U.S. GFT
      model by comparing weekly estimates of ILI (influenza-like illness) activity with
      the U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet). For
      each GFT model we calculated the correlation and RMSE (root mean square error)
      between model estimates and ILINet for four time periods: pre-H1N1, Summer H1N1,
      Winter H1N1, and H1N1 overall (Mar 2009-Dec 2009). We also compared the number of
      queries, query volume, and types of queries (e.g., influenza symptoms, influenza
      complications) in each model. Both models' estimates were highly correlated with
      ILINet pre-H1N1 and over the entire surveillance period, although the original
      model underestimated the magnitude of ILI activity during pH1N1. The updated
      model was more correlated with ILINet than the original model during Summer H1N1
      (r = 0.95 and 0.29, respectively). The updated model included more search query
      terms than the original model, with more queries directly related to influenza
      infection, whereas the original model contained more queries related to influenza
      complications. CONCLUSIONS: Internet search behavior changed during pH1N1,
      particularly in the categories "influenza complications" and "term for
      influenza." The complications associated with pH1N1, the fact that pH1N1 began in
      the summer rather than winter, and changes in health-seeking behavior each may
      have played a part. Both GFT models performed well prior to and during pH1N1,
      although the updated model performed better during pH1N1, especially during the
      summer months.

PMID- 21886803
TI  - Reverse transcriptase-coupled quantitative real time PCR analysis of cell-free
      transcription on the chromatin-assembled p21 promoter.
AB  - BACKGROUND: Cell-free eukaryotic transcription assays have contributed
      tremendously to the current understanding of the molecular mechanisms that govern
      transcription at eukaryotic promoters. Currently, the conventional G-less
      cassette transcription assay is one of the simplest and fastest methods for
      measuring transcription in vitro. This method requires several components,
      including the radioisotope labelling of RNA product during the transcription
      reaction followed by visualization of transcripts using autoradiography.
      METHODOLOGY/PRINCIPAL FINDINGS: To further simplify and expedite the conventional
      G-less cassette transcription assay, we have developed a method to incorporate a
      reverse transcriptase-coupled quantitative real time PCR (RT-qPCR). By using DNA
      template depletion steps that include DNA template immobilization, Trizol
      extraction and DNase I treatment, we have successfully enriched p21 promoter
      driven transcripts over DNA templates. The quantification results of RNA
      transcripts using the RT-qPCR assay were comparable to the results of the
      conventional G-less cassette transcription assay both in naked DNA and chromatin
      assembled templates. CONCLUSIONS: We first report a proof-of-concept
      demonstration that incorporating RT-qPCR in cell-free transcription assays can be
      a simpler and faster alternative method to the conventional radioisotope-mediated
      transcription assays. This method will be useful for developing high throughput
      in vitro transcription assays and provide quantitative data for RNA transcripts
      generated in a defined cell-free transcription reaction.

PMID- 21886804
TI  - In vivo induction of Tr1 cells via mucosal dendritic cells and AHR signaling.
AB  - BACKGROUND: Type 1 regulatory T (Tr1) cells, characterized by the secretion of
      high levels of the anti-inflammatory cytokine interleukin-10 (IL-10), play an
      important role in the regulation of autoimmune diseases and transplantation.
      However, effective strategies that specifically induce Tr1 cells in vivo are
      limited. Furthermore, the pathways controlling the induction of these cells in
      vivo are not well understood. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that
      nasal administration of anti-CD3 antibody induces suppressive Tr1 cells in mice.
      The in vivo induction of Tr1 cells by nasal anti-CD3 is dependent on IL-27
      produced by upper airway resident dendritic cells (DCs), and is controlled by the
      transcription factors aryl hydrocarbon receptor (AHR) and c-Maf. Subsequently, IL
      21 acts in an autocrine fashion to expand and maintain the Tr1 cells induced in
      vivo by nasally administered anti-CD3. CONCLUSIONS/SIGNIFICANCE: Our findings
      identify a unique approach to generate Tr1 cells in vivo and provide insights
      into the mechanisms by which these cells are induced.

PMID- 21886805
TI  - Nasopharyngeal colonization and invasive disease are enhanced by the cell wall
      hydrolases LytB and LytC of Streptococcus pneumoniae.
AB  - BACKGROUND: Streptococcus pneumoniae is a common colonizer of the human
      nasopharynx and one of the major pathogens causing invasive disease worldwide.
      Dissection of the molecular pathways responsible for colonization, invasion, and
      evasion of the immune system will provide new targets for antimicrobial or
      vaccine therapies for this common pathogen. METHODOLOGY/PRINCIPAL FINDINGS: We
      have constructed mutants lacking the pneumococcal cell wall hydrolases (CWHs)
      LytB and LytC to investigate the role of these proteins in different phases of
      the pneumococcal pathogenesis. Our results show that LytB and LytC are involved
      in the attachment of S. pneumoniae to human nasopharyngeal cells both in vitro
      and in vivo. The interaction of both proteins with phagocytic cells demonstrated
      that LytB and LytC act in concert avoiding pneumococcal phagocytosis mediated by
      neutrophils and alveolar macrophages. Furthermore, C3b deposition was increased
      on the lytC mutant confirming that LytC is involved in complement evasion. As a
      result, the lytC mutant showed a reduced ability to successfully cause
      pneumococcal pneumonia and sepsis. Bacterial mutants lacking both LytB and LytC
      showed a dramatically impaired attachment to nasopharyngeal cells as well as a
      marked degree of attenuation in a mouse model of colonization. In addition, C3b
      deposition and phagocytosis was more efficient for the double lytB lytC mutant
      and its virulence was greatly impaired in both systemic and pulmonary models of
      infection. CONCLUSIONS/SIGNIFICANCE: This study confirms that the CWHs LytB and
      LytC of S. pneumoniae are essential virulence factors involved in the
      colonization of the nasopharynx and in the progress of invasive disease by
      avoiding host immunity.

PMID- 21886806
TI  - Search for specific biomarkers of IFNbeta bioactivity in patients with multiple
      sclerosis.
AB  - Myxovirus A (MxA), a protein encoded by the MX1 gene with antiviral activity, has
      proven to be a sensitive measure of IFNbeta bioactivity in multiple sclerosis
      (MS). However, the use of MxA as a biomarker of IFNbeta bioactivity has been
      criticized for the lack of evidence of its role on disease pathogenesis and the
      clinical response to IFNbeta. Here, we aimed to identify specific biomarkers of
      IFNbeta bioactivity in order to compare their gene expression induction by type I
      IFNs with the MxA, and to investigate their potential role in MS pathogenesis.
      Gene expression microarrays were performed in PBMC from MS patients who developed
      neutralizing antibodies (NAB) to IFNbeta at 12 and/or 24 months of treatment and
      patients who remained NAB negative. Nine genes followed patterns in gene
      expression over time similar to the MX1, which was considered the gold standard
      gene, and were selected for further experiments: IFI6, IFI27, IFI44L, IFIT1,
      HERC5, LY6E, RSAD2, SIGLEC1, and USP18. In vitro experiments in PBMC from healthy
      controls revealed specific induction of selected biomarkers by IFNbeta but not
      IFNgamma, and several markers, in particular USP18 and HERC5, were shown to be
      significantly induced at lower IFNbeta concentrations and more selective than the
      MX1 as biomarkers of IFNbeta bioactivity. In addition, USP18 expression was
      deficient in MS patients compared with healthy controls (p = 0.0004). We propose
      specific biomarkers that may be considered in addition to the MxA to evaluate
      IFNbeta bioactivity, and to further explore their implication in MS pathogenesis.

PMID- 21886807
TI  - The homolog of the five SH3-domain protein (HOFI/SH3PXD2B) regulates lamellipodia
      formation and cell spreading.
AB  - Motility of normal and transformed cells within and across tissues requires
      specialized subcellular structures, e.g. membrane ruffles, lamellipodia and
      podosomes, which are generated by dynamic rearrangements of the actin
      cytoskeleton. Because the formation of these sub-cellular structures is complex
      and relatively poorly understood, we evaluated the role of the adapter protein
      SH3PXD2B [HOFI, fad49, Tks4], which plays a role in the development of the eye,
      skeleton and adipose tissue. Surprisingly, we find that SH3PXD2B is requisite for
      the development of EGF-induced membrane ruffles and lamellipodia, as well as for
      efficient cellular attachment and spreading of HeLa cells. Furthermore, SH3PXD2B
      is present in a complex with the non-receptor protein tyrosine kinase Src,
      phosphorylated by Src, which is consistent with SH3PXD2B accumulating in Src
      induced podosomes. Furthermore, SH3PXD2B closely follows the subcellular
      relocalization of cortactin to Src-induced podosomes, EGF-induced membrane
      ruffles and lamellipodia. Because SH3PXD2B also forms a complex with the C
      terminal region of cortactin, we propose that SH3PXD2B is a scaffold protein that
      plays a key role in regulating the actin cytoskeleton via Src and cortactin.

PMID- 21886808
TI  - Impact of collection method on assessment of semen HIV RNA viral load.
AB  - BACKGROUND: The blood HIV RNA viral load is the best-defined predictor of HIV
      transmission, in part due to ease of measurement and the correlation of blood and
      genital tract (semen or cervico-vaginal) viral load, although recent studies
      found semen HIV RNA concentration to be a stronger predictor of HIV transmission.
      There is currently no standardized method for semen collection when measuring HIV
      RNA concentration. Therefore, we compared two collection techniques in order to
      study of the impact of antiretroviral therapy on the semen viral load.
      METHODOLOGY/PRINCIPAL FINDINGS: Semen was collected by masturbation from HIV
      infected, therapy-naive men who have sex with men (MSM) either undiluted (Visit
      1) or directly into transport medium (Visit 2). Seminal plasma was then isolated,
      and the HIV RNA concentration obtained with each collection technique was
      measured and corrected for dilution if necessary. Collection of semen directly
      into transport medium resulted in a median HIV RNA viral load that was 0.4 log10
      higher than undiluted samples. CONCLUSIONS/SIGNIFICANCE: The method of semen
      collection is an important consideration when quantifying the HIV RNA viral load
      in this compartment.

PMID- 21886809
TI  - Efficient non-viral reprogramming of myoblasts to stemness with a single small
      molecule to generate cardiac progenitor cells.
AB  - The current protocols for generation of induced pluripotent stem (iPS) cells
      involve genome integrating viral vectors which may induce tumorgenesis. The aim
      of this study was to develop and optimize a non-viral method without genetic
      manipulation for reprogramming of skeletal myoblasts (SMs) using small molecules.
      METHODS AND RESULTS: SMs from young male Oct3/4-GFP(+) transgenic mouse were
      treated with DNA methyltransferase (DNMT) inhibitor, RG108. Two weeks later,
      GFP(+) colonies of SM derived iPS cells (SiPS) expressing GFP and with
      morphological similarity of mouse embryonic stem (ESCs) were formed and
      propagated in vitro. SiPS were positive for alkaline phosphatase activity,
      expressed SSEA1, displayed ES cell specific pluripotency markers and formed
      teratoma in nude mice. Optimization of culture conditions for embryoid body (EBs)
      formation yielded spontaneously contracting EBs having morphological, molecular,
      and ultra-structural similarities with cardiomyocytes and expressed early and
      late cardiac markers. miR profiling showed abrogation of let-7 family and
      upregulation of ESCs specific miR-290-295 cluster thus indicating that SiPS were
      similar to ESCs in miR profile. Four weeks after transplantation into the
      immunocompetent mice model of acute myocardial infarction (n = 12 per group),
      extensive myogenesis was observed in SiPS transplanted hearts as compared to DMEM
      controls (n = 6 per group). A significant reduction in fibrosis and improvement
      in global heart function in the hearts transplanted with SiPS derived cardiac
      progenitor cells were observed. CONCLUSIONS: Reprogramming of SMs by DNMT
      inhibitor is a simple, reproducible and efficient technique more likely to
      generate transgene integration-free iPS cells. Cardiac progenitors derived from
      iPS cells propagated extensively in the infarcted myocardium without tumorgenesis
      and improved cardiac function.

PMID- 21886810
TI  - APC(cdh1) mediates degradation of the oncogenic Rho-GEF Ect2 after mitosis.
AB  - BACKGROUND: Besides regulation of actin cytoskeleton-dependent functions, Rho
      GTPase pathways are essential to cell cycle progression and cell division. Rho,
      Rac and Cdc42 regulate G1 to S phase progression and are involved in cytokinesis.
      RhoA GDP/GTP cycling is required for normal cytokinesis and recent reports have
      shown that the exchange factor Ect2 and the GTPase activating protein MgcRacGAP
      regulate RhoA activity during mitosis. We previously showed that the
      transcription factors E2F1 and CUX1 regulate expression of MgcRacGAP and Ect2 as
      cells enter S-phase. METHODOLOGY/PRINCIPAL FINDINGS: We now report that Ect2 is
      subject to proteasomal degradation after mitosis, following ubiquitination by the
      APC/C complex and its co-activator Cdh1. A proper nuclear localization of Ect2 is
      necessary for its degradation. APC-Cdh1 assembles K11-linked poly-ubiquitin
      chains on Ect2, depending upon a stretch of ~25 amino acid residues that contain
      a bi-partite NLS, a conventional D-box and two TEK-like boxes. Site-directed
      mutagenesis of target sequences generated stabilized Ect2 proteins. Furthermore,
      such degradation-resistant mutants of Ect2 were found to activate RhoA and
      subsequent signalling pathways and are able to transform NIH3T3 cells.
      CONCLUSIONS/SIGNIFICANCE: Our results identify Ect2 as a bona fide cell cycle
      regulated protein and suggest that its ubiquitination-dependent degradation may
      play an important role in RhoA regulation at the time of mitosis. Our findings
      raise the possibility that the overexpression of Ect2 that has been reported in
      some human tumors might result not only from deregulated transcription, but also
      from impaired degradation.

PMID- 21886811
TI  - Functional assessment of EnvZ/OmpR two-component system in Shewanella oneidensis.
AB  - EnvZ and OmpR constitute the bacterial two-component signal transduction system
      known to mediate osmotic stress response in a number of gram-negative bacteria.
      In an effort to understand the mechanism through which Shewanella oneidensis
      senses and responds to environmental osmolarity changes, structure of the ompR
      envZ operon was determined with Northern blotting assay and roles of the
      EnvZ/OmpR two-component system in response to various stresses were investigated
      with mutational analysis, quantitative reverse transcriptase PCR (qRT-PCR), and
      phenotype microarrays. Results from the mutational analysis and qRT-PCR suggested
      that the EnvZ/OmpR system contributed to osmotic stress response of S. oneidensis
      and very likely engaged a similar strategy employed by E. coli, which involved
      reciprocal regulation of two major porin coding genes. Additionally, the ompR
      envZ system was also found related to cell motility. We further showed that the
      ompR-envZ dependent regulation of porin genes and motility resided almost
      completely on ompR and only partially on envZ, indicating additional mechanisms
      for OmpR phosphorylation. In contrast to E. coli lacking ompR-envZ, however,
      growth of S. oneidensis did not show a significant dependence on ompR-envZ even
      under osmotic stress. Further analysis with phenotype microarrays revealed that
      the S. oneidensis strains lacking a complete ompR-envZ system displayed
      hypersensitivities to a number of agents, especially in alkaline environment.
      Taken together, our results suggest that the function of the ompR-envZ system in
      S. oneidensis, although still connected with osmoregulation, has diverged
      considerably from that of E. coli. Additional mechanism must exist to support
      growth of S. oneidensis under osmotic stress.

PMID- 21886812
TI  - Transduction of SIV-specific TCR genes into rhesus macaque CD8+ T cells conveys
      the ability to suppress SIV replication.
AB  - BACKGROUND: The SIV/rhesus macaque model for HIV/AIDS is a powerful system for
      examining the contribution of T cells in the control of AIDS viruses. To better
      our understanding of CD8(+) T-cell control of SIV replication in CD4(+) T cells,
      we asked whether TCRs isolated from rhesus macaque CD8(+) T-cell clones that
      exhibited varying abilities to suppress SIV replication could convey their
      suppressive properties to CD8(+) T cells obtained from an uninfected/unvaccinated
      animal. PRINCIPAL FINDINGS: We transferred SIV-specific TCR genes isolated from
      rhesus macaque CD8(+) T-cell clones with varying abilities to suppress SIV
      replication in vitro into CD8(+) T cells obtained from an uninfected animal by
      retroviral transduction. After sorting and expansion, transduced CD8(+) T-cell
      lines were obtained that specifically bound their cognate SIV tetramer. These
      cell lines displayed appropriate effector function and specificity, expressing
      intracellular IFNgamma upon peptide stimulation. Importantly, the SIV suppression
      properties of the transduced cell lines mirrored those of the original TCR donor
      clones: cell lines expressing TCRs transferred from highly suppressive clones
      effectively reduced wild-type SIV replication, while expression of a non
      suppressing TCR failed to reduce the spread of virus. However, all TCRs were able
      to suppress the replication of an SIV mutant that did not downregulate MHC-I,
      recapitulating the properties of their donor clones. CONCLUSIONS: Our results
      show that antigen-specific SIV suppression can be transferred between allogenic T
      cells simply by TCR gene transfer. This advance provides a platform for examining
      the contributions of TCRs versus the intrinsic effector characteristics of T-cell
      clones in virus suppression. Additionally, this approach can be applied to
      develop non-human primate models to evaluate adoptive T-cell transfer therapy for
      AIDS and other diseases.

PMID- 21886813
TI  - The targeting of plasmalemmal ceramide to mitochondria during apoptosis.
AB  - Ceramide is a key lipid mediator of cellular processes such as differentiation,
      proliferation, growth arrest and apoptosis. During apoptosis, ceramide is
      produced within the plasma membrane. Although recent data suggest that the
      generation of intracellular ceramide increases mitochondrial permeability, the
      source of mitochondrial ceramide remains unknown. Here, we determine whether a
      stress-mediated plasmalemmal pool of ceramide might become available to the
      mitochondria of apoptotic cells. We have previously established annexin A1--a
      member of a family of Ca(2+) and membrane-binding proteins--to be a marker of
      ceramide platforms. Using fluorescently tagged annexin A1, we show that, upon its
      generation within the plasma membrane, ceramide self-associates into platforms
      that subsequently invaginate and fuse with mitochondria. An accumulation of
      ceramide within the mitochondria of apoptotic cells was also confirmed using a
      ceramide-specific antibody. Electron microscopic tomography confirmed that upon
      the formation of ceramide platforms, the invaginated regions of the plasma
      membrane extend deep into the cytoplasm forming direct physical contacts with
      mitochondrial outer membranes. Ceramide might thus be directly transferred from
      the plasma membrane to the mitochondrial outer membrane. It is conceivable that
      this "kiss-of-death" increases the permeability of the mitochondrial outer
      membrane thereby triggering apoptosis.

PMID- 21886815
TI  - Circulating endoglin concentration is not elevated in chronic kidney disease.
AB  - BACKGROUND: Soluble endoglin, a TGF-beta receptor, plays a key role in
      cardiovascular physiology. Whether circulating concentrations of soluble endoglin
      are elevated in CKD or underlie the high risk of cardiovascular death associated
      with chronic kidney disease (CKD) is unknown. METHODS: Individuals with and
      without CKD were recruited at a single center. Estimated glomerular filtration
      rate (eGFR) was estimated using the modified MDRD study equation and the serum
      creatinine at the time of recruitment, and patients were assigned to specific CKD
      stage according to usual guidelines. Serum endoglin concentration was measured by
      ELISA and univariate and multivariable regression was used to analyze the
      association between eGFR or CKD stage and the concentration of soluble endoglin.
      RESULTS: Serum endoglin was measured in 216 patients including 118 with stage 3
      or higher CKD and 9 individuals with end stage renal disease (ESRD). Serum
      endoglin concentration did not vary significantly with CKD stage (increase of
      0.16 ng/mL per 1 stage increase in CKD, P = 0.09) or eGFR (decrease -0.06 ng/mL
      per 10 mL/min/1.73 m(2) increase in GFR, P = 0.12), and was not higher in
      individuals with ESRD than in individuals with preserved renal function (4.2+/
      1.1 and 4.3+/-1.2 ng/mL, respectively). Endoglin concentration was also not
      significantly associated with urinary albumin excretion. CONCLUSIONS: Renal
      function is not associated with the circulating concentration of soluble
      endoglin. Elevations in soluble endoglin concentration are unlikely to contribute
      to the progression of CKD or the predisposition of individuals with CKD to
      develop cardiovascular disease.

PMID- 21886814
TI  - Novel inducers of the envelope stress response BaeSR in Salmonella Typhimurium:
      BaeR is critically required for tungstate waste disposal.
AB  - The RpoE and CpxR regulated envelope stress responses are extremely important for
      Salmonella Typhimurium to cause infection in a range of hosts. Until now the role
      for BaeSR in both the Salmonella Typhimurium response to stress and its
      contribution to infection have not been fully elucidated. Here we demonstrate
      stationary phase growth, iron and sodium tungstate as novel inducers of the
      BaeRregulon, with BaeR critically required for Salmonella resistance to sodium
      tungstate. We show that functional overlap between the resistance nodulation-cell
      division (RND) multidrug transporters, MdtA, AcrD and AcrB exists for the waste
      disposal of tungstate from the cell. We also point to a role for
      enterobactinsiderophores in the protection of enteric organisms from tungstate,
      akin to the scenario in nitrogen fixing bacteria. Surprisingly, BaeR is the first
      envelope stress response pathway investigated in S. Typhimurium that is not
      required for murine typhoid in either ity(S) or ity(R) mouse backgrounds. BaeR is
      therefore either required for survival in larger mammals such as pigs or calves,
      an avian host such as chickens, or survival out with the host altogether where
      Salmonella and related enterics must survive in soil and water.

PMID- 21886816
TI  - Pilot, randomized study assessing safety, tolerability and efficacy of simplified
      LPV/r maintenance therapy in HIV patients on the 1 PI-based regimen.
AB  - OBJECTIVES: To compare the efficacy and safety of an individualized treatment
      simplification strategy consisting of switching from a highly-active anti
      retroviral treatment (HAART) with a ritonavir-boosted protease inhibitor (PI/r)
      and 2 nucleoside reverse-transcriptase inhibitors (NRTIs) to lopinavir/ritonavir
      (LPV/r) monotherapy, with intensification by 2 NRTIs if necessary, to that of
      continuing their HAART. METHODS: This is a one-year, randomized, open-label,
      multi-center study in virologically-suppressed HIV-1-infected adults on their
      first PI/r-containing treatment, randomized to either LPV/r-monotherapy or
      continue their current treatment. Treatment efficacy was determined by plasma HIV
      1 RNA viral load (VL), time-to-virologic rebound, patient-reported outcomes
      (PROs) and CD4+T-cell-count changes. Safety was assessed with the incidence of
      treatment-emergent adverse events (AE). RESULTS: Forty-one patients were
      randomized to LPV/r and 39 to continue their HAART. No statistically-significant
      differences between the two study groups in demographics and baseline
      characteristics were observed. At day-360, 71(39:LPV/r;32:HAART) patients
      completed treatment, while 9(2:LPV/r;7:HAART) discontinued. In a Last Observation
      Carried Forward Intent-to-Treat analysis, 40(98%) patients on LPV/r and 37(95%)
      on HAART had VL<200 copies/mL (P = 0.61). Time-to-virologic rebound, changes in
      PROs, CD4+ T-cell-count and VL from baseline, also exhibited no statistically
      significant between-group differences. Most frequent AEs were diarrhea (19%),
      headache (18%) and influenza (16%). Four (10%) patients on LPV/r were intensified
      with 2 NRTIs, all regaining virologic control. Eight serious AEs were reported by
      5(2:LPV/r;3:HAART) patients. CONCLUSION: At day-360, virologic efficacy and
      safety of LPV/r appears comparable to that of a PI+2NRTIs HAART. These results
      suggest that our individualized, simplified maintenance strategy with LPV/r
      monotherapy and protocol-mandated NRTI re-introduction upon viral rebound, in
      virologically-suppressed patients merits further prospective long-term
      evaluation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00159224.

PMID- 21886817
TI  - A plant DJ-1 homolog is essential for Arabidopsis thaliana chloroplast
      development.
AB  - Protein superfamilies can exhibit considerable diversification of function among
      their members in various organisms. The DJ-1 superfamily is composed of proteins
      that are principally involved in stress response and are widely distributed in
      all kingdoms of life. The model flowering plant Arabidopsis thaliana contains
      three close homologs of animal DJ-1, all of which are tandem duplications of the
      DJ-1 domain. Consequently, the plant DJ-1 homologs are likely pseudo-dimeric
      proteins composed of a single polypeptide chain. We report that one A. thaliana
      DJ-1 homolog (AtDJ1C) is the first DJ-1 homolog in any organism that is required
      for viability. Homozygous disruption of the AtDJ1C gene results in non-viable,
      albino seedlings that can be complemented by expression of wild-type or epitope
      tagged AtDJ1C. The plastids from these dj1c plants lack thylakoid membranes and
      granal stacks, indicating that AtDJ1C is required for proper chloroplast
      development. AtDJ1C is expressed early in leaf development when chloroplasts
      mature, but is downregulated in older tissue, consistent with a proposed role in
      plastid development. In addition to its plant-specific function, AtDJ1C is an
      atypical member of the DJ-1 superfamily that lacks a conserved cysteine residue
      that is required for the functions of most other superfamily members. The
      essential role for AtDJ1C in chloroplast maturation expands the known functional
      diversity of the DJ-1 superfamily and provides the first evidence of a role for
      specialized DJ-1-like proteins in eukaryotic development.

PMID- 21886818
TI  - The Candida albicans Ku70 modulates telomere length and structure by regulating
      both telomerase and recombination.
AB  - The heterodimeric Ku complex has been shown to participate in DNA repair and
      telomere regulation in a variety of organisms. Here we report a detailed
      characterization of the function of Ku70 in the diploid fungal pathogen Candida
      albicans. Both ku70 heterozygous and homozygous deletion mutants have a wild-type
      colony and cellular morphology, and are not sensitive to MMS or UV light.
      Interestingly, we observed complex effects of KU70 gene dosage on telomere
      lengths, with the KU70/ku70 heterozygotes exhibiting slightly shorter telomeres,
      and the ku70 null strain exhibiting long and heterogeneous telomeres. Analysis of
      combination mutants suggests that the telomere elongation in the ku70 null mutant
      is due mostly to unregulated telomerase action. In addition, elevated levels of
      extrachromosomal telomeric circles were detected in the null mutant, consistent
      with activation of aberrant telomeric recombination. Altogether, our observations
      point to multiple mechanisms of the Ku complex in telomerase regulation and
      telomere protection in C. albicans, and reveal interesting similarities and
      differences in the mechanisms of the Ku complex in disparate systems.

PMID- 21886819
TI  - The magnitude and kinetics of the mucosal HIV-specific CD8+ T lymphocyte response
      and virus RNA load in breast milk.
AB  - BACKGROUND: The risk of postnatal HIV transmission is associated with the
      magnitude of the milk virus load. While HIV-specific cellular immune responses
      control systemic virus load and are detectable in milk, the contribution of these
      responses to the control of virus load in milk is unknown. METHODS: We assessed
      the magnitude of the immunodominant GagRY11 and subdominant EnvKY9-specific CD8+
      T lymphocyte response in blood and milk of 10 A*3002+, HIV-infected Malawian
      women throughout the period of lactation and correlated this response to milk
      virus RNA load and markers of breast inflammation. RESULTS: The magnitude and
      kinetics of the HIV-specific CD8+ T lymphocyte responses were discordant in blood
      and milk of the right and left breast, indicating independent regulation of these
      responses in each breast. However, there was no correlation between the magnitude
      of the HIV-specific CD8+ T lymphocyte response and the milk virus RNA load.
      Further, there was no correlation between the magnitude of this response and
      markers of breast inflammation. CONCLUSIONS: The magnitude of the HIV-specific
      CD8+ T lymphocyte response in milk does not appear to be solely determined by the
      milk virus RNA load and is likely only one of the factors contributing to
      maintenance of low virus load in milk.

PMID- 21886820
TI  - Structural brain changes related to disease duration in patients with asthma.
AB  - Dyspnea is the impairing, cardinal symptom patients with asthma repeatedly
      experience over the course of the disease. However, its accurate perception is
      also crucial for timely initiation of treatment. Reduced perception of dyspnea is
      associated with negative treatment outcome, but the underlying brain mechanisms
      of perceived dyspnea in patients with asthma remain poorly understood. We
      examined whether increasing disease duration in fourteen patients with mild-to
      moderate asthma is related to structural brain changes in the insular cortex and
      brainstem periaqueductal grey (PAG). In addition, the association between
      structural brain changes and perceived dyspnea were studied. By using magnetic
      resonance imaging in combination with voxel-based morphometry, gray matter
      volumes of the insular cortex and the PAG were analysed and correlated with
      asthma duration and perceived affective unpleasantness of resistive load induced
      dyspnea. Whereas no associations were observed for the insular cortex, longer
      duration of asthma was associated with increased gray matter volume in the PAG.
      Moreover, increased PAG gray matter volume was related to reduced ratings of
      dyspnea unpleasantness. Our results demonstrate that increasing disease duration
      is associated with increased gray matter volume in the brainstem PAG in patients
      with mild-to-moderate asthma. This structural brain change might contribute to
      the reduced perception of dyspnea in some patients with asthma and negatively
      impact the treatment outcome.

PMID- 21886821
TI  - Fine-scale variation in vector host use and force of infection drive localized
      patterns of West Nile virus transmission.
AB  - The influence of host diversity on multi-host pathogen transmission and
      persistence can be confounded by the large number of species and biological
      interactions that can characterize many transmission systems. For vector-borne
      pathogens, the composition of host communities has been hypothesized to affect
      transmission; however, the specific characteristics of host communities that
      affect transmission remain largely unknown. We tested the hypothesis that vector
      host use and force of infection (i.e., the summed number of infectious mosquitoes
      resulting from feeding upon each vertebrate host within a community of hosts),
      and not simply host diversity or richness, determine local infection rates of
      West Nile virus (WNV) in mosquito vectors. In suburban Chicago, Illinois, USA, we
      estimated community force of infection for West Nile virus using data on Culex
      pipiens mosquito host selection and WNV vertebrate reservoir competence for each
      host species in multiple residential and semi-natural study sites. We found host
      community force of infection interacted with avian diversity to influence WNV
      infection in Culex mosquitoes across the study area. Two avian species, the
      American robin (Turdus migratorius) and the house sparrow (Passer domesticus),
      produced 95.8% of the infectious Cx. pipiens mosquitoes and showed a significant
      positive association with WNV infection in Culex spp. mosquitoes. Therefore,
      indices of community structure, such as species diversity or richness, may not be
      reliable indicators of transmission risk at fine spatial scales in vector-borne
      disease systems. Rather, robust assessment of local transmission risk should
      incorporate heterogeneity in vector host feeding and variation in vertebrate
      reservoir competence at the spatial scale of vector-host interaction.

PMID- 21886822
TI  - Expression of cystathionine beta-synthase and cystathionine gamma-lyase in human
      pregnant myometrium and their roles in the control of uterine contractility.
AB  - BACKGROUND: Human uterus undergoes distinct molecular and functional changes
      during pregnancy and parturition. Hydrogen sulfide (H(2)S) has recently been
      shown to play a key role in the control of smooth muscle tension. The role of
      endogenous H(2)S produced locally in the control of uterine contractility during
      labour is unknown. METHODOLOGY/PRINCIPAL FINDINGS: Human myometrium biopsies were
      obtained from pregnant women undergoing cesarean section at term.
      Immunohistochemistry analysis showed that cystathionine-gamma-lyase (CSE) and
      cystathionine-beta-synthetase (CBS), the principle enzymes responsible for H(2)S
      generation, were mainly localized to smooth muscle cells of human pregnant
      myometrium. The mRNA and protein expression of CBS as well as H(2)S production
      rate were down-regulated in labouring tissues compared to nonlabouring tissues.
      Cumulative administration of L-cysteine (10(-7)-10(-2) mol/L), a precursor of
      H(2)S, caused a dose-dependent decrease in the amplitude of spontaneous
      contractions in nonlabouring and labouring myometrium strips. L-cysteine at high
      concentration (10(-3) mol/L) increased the frequency of spontaneous contractions
      and induced tonic contraction. These effects of L-cysteine were blocked by the
      inhibitors of CBS and CSE. Pre-treatment of myometrium strips with glibenclamide,
      an inhibitor of ATP-sensitive potassium (K(ATP)) channels, abolished the
      inhibitory effect of L-cysteine on spontaneous contraction amplitude. The effects
      of L-cysteine on the amplitude of spontaneous contractions and baseline muscle
      tone were less potent in labouring tissues than that in nonlabouring strips.
      CONCLUSION/SIGNIFICANCE: H(2)S generated by CSE and CBS locally exerts dual
      effects on the contractility of pregnant myometrium. Expression of H(2)S
      synthetic enzymes is down-regulated during labour, suggesting that H(2)S is one
      of the factors involved in the transition of pregnant uterus from quiescence to
      contractile state after onset of parturition.

PMID- 21886823
TI  - Iron uptake mediated by binding of H-ferritin to the TIM-2 receptor in mouse
      cells.
AB  - Ferritin binds specifically and saturably to a variety of cell types, and
      recently several ferritin receptors have been cloned. TIM-2 is a specific
      receptor for H ferritin (HFt) in the mouse. TIM-2 is a member of the T cell
      immunoglobulin and mucin domain containing (TIM) protein family and plays an
      important role in immunity. The expression of TIM-2 outside of the immune system
      indicates that this receptor may have broader roles. We tested whether ferritin
      binding to TIM-2 can serve as an iron delivery mechanism. TIM-2 was transfected
      into normal (TCMK-1) mouse kidney cells, where it was appropriately expressed on
      the cell surface. HFt was labeled with (55)Fe and (55)Fe-HFt was incubated with
      TIM-2 positive cells or controls. (55)Fe-HFt uptake was observed only in TIM-2
      positive cells. HFt uptake was also seen in A20 B cells, which express endogenous
      TIM-2. TIM-2 levels were not increased by iron chelation. Uptake of (55)Fe-HFt
      was specific and temperature-dependent. HFt taken up by TIM-2 positive cells
      transited through the endosome and eventually entered a lysosomal compartment,
      distinguishing the HFt pathway from that of transferrin, the classical vehicle
      for cellular iron delivery. Iron delivered following binding of HFt to TIM-2
      entered the cytosol and became metabolically available, resulting in increased
      levels of endogenous intracellular ferritin. We conclude that TIM-2 can function
      as an iron uptake pathway.

PMID- 21886824
TI  - Analysis of factors lowering sensitivity of interferon-gamma release assay for
      tuberculosis.
AB  - BACKGROUND: Imperfect sensitivity of interferon-gamma release assay (IGRA) is a
      potential problem to detect tuberculosis. We made a thorough investigation of the
      factors that can lead to false negativity of IGRA. METHODS: We recruited 543
      patients with new smear-positive pulmonary tuberculosis in Hanoi, Viet Nam. At
      diagnosis, peripheral blood was collected and IGRA (QuantiFERON-TB Gold In-Tube)
      was performed. Clinical and epidemiological information of the host and pathogen
      was collected. The test sensitivity was calculated and factors negatively
      influencing IGRA results were evaluated using a logistic regression model in 504
      patients with culture-confirmed pulmonary tuberculosis. RESULTS: The overall
      sensitivity of IGRA was 92.3% (95% CI, 89.6%-94.4%). The proportions of IGRA
      negative and -indeterminate results were 4.8% (95% CI, 3.1%-7.0%) and 3.0% (95%
      CI, 1.7%-4.9%). Age increased by year, body mass index <16.0, HIV co-infection
      and the increased number of HLA-DRB1*0701 allele that patients bear showed
      significant associations with IGRA negativity (OR = 1.04 [95% CI, 1.01-1.07],
      5.42 [1.48-19.79], 6.38 [1.78-22.92] and 5.09 [2.31-11.22], respectively). HIV co
      infection and the same HLA allele were also associated with indeterminate results
      (OR = 99.59 [95% CI, 15.58-625.61] and 4.25 [1.27-14.16]). CONCLUSIONS: Aging,
      emaciation, HIV co-infection and HLA genotype affected IGRA results. Assessment
      of these factors might contribute to a better understanding of the assay.

PMID- 21886825
TI  - Very low tidal volume ventilation with associated hypercapnia--effects on lung
      injury in a model for acute respiratory distress syndrome.
AB  - BACKGROUND: Ventilation using low tidal volumes with permission of hypercapnia is
      recommended to protect the lung in acute respiratory distress syndrome. However,
      the most lung protective tidal volume in association with hypercapnia is unknown.
      The aim of this study was to assess the effects of different tidal volumes with
      associated hypercapnia on lung injury and gas exchange in a model for acute
      respiratory distress syndrome. METHODOLOGY/PRINCIPAL FINDINGS: In this randomized
      controlled experiment sixty-four surfactant-depleted rabbits were exposed to 6
      hours of mechanical ventilation with the following targets: Group 1: tidal volume
      = 8-10 ml/kg/PaCO(2) = 40 mm Hg; Group 2: tidal volume = 4-5 ml/kg/PaCO(2) = 80
      mm Hg; Group 3: tidal volume = 3-4 ml/kg/PaCO(2) = 120 mm Hg; Group 4: tidal
      volume = 2-3 ml/kg/PaCO(2) = 160 mm Hg. Decreased wet-dry weight ratios of the
      lungs, lower histological lung injury scores and higher PaO(2) were found in all
      low tidal volume/hypercapnia groups (group 2, 3, 4) as compared to the group with
      conventional tidal volume/normocapnia (group 1). The reduction of the tidal
      volume below 4-5 ml/kg did not enhance lung protection. However, oxygenation and
      lung protection were maintained at extremely low tidal volumes in association
      with very severe hypercapnia and no adverse hemodynamic effects were observed
      with this strategy. CONCLUSION: Ventilation with low tidal volumes and associated
      hypercapnia was lung protective. A tidal volume below 4-5 ml/kg/PaCO(2) 80 mm Hg
      with concomitant more severe hypercapnic acidosis did not increase lung
      protection in this surfactant deficiency model. However, even at extremely low
      tidal volumes in association with severe hypercapnia lung protection and
      oxygenation were maintained.

PMID- 21886826
TI  - Elevated plasma corticosterone decreases yolk testosterone and progesterone in
      chickens: linking maternal stress and hormone-mediated maternal effects.
AB  - Despite considerable research on hormone-mediated maternal effects in birds, the
      underlying physiology remains poorly understood. This study investigated a
      potential regulation mechanism for differential accumulation of gonadal hormones
      in bird eggs. Across vertebrates, glucocorticoids can suppress reproduction by
      downregulating gonadal hormones. Using the chicken as a model species, we
      therefore tested whether elevated levels of plasma corticosterone in female birds
      influence the production of gonadal steroids by the ovarian follicles and thus
      the amount of reproductive hormones in the egg yolk. Adult laying hens of two
      different strains (ISA brown and white Leghorn) were implanted subcutaneously
      with corticosterone pellets that elevated plasma corticosterone concentrations
      over a period of nine days. Steroid hormones were subsequently quantified in
      plasma and yolk. Corticosterone-implanted hens of both strains had lower plasma
      progesterone and testosterone levels and their yolks contained less progesterone
      and testosterone. The treatment also reduced egg and yolk mass. Plasma estrogen
      concentrations decreased in white Leghorns only whereas in both strains yolk
      estrogens were unaffected. Our results demonstrate for the first time that
      maternal plasma corticosterone levels influence reproductive hormone
      concentrations in the yolk. Maternal corticosterone could therefore mediate
      environmentally induced changes in yolk gonadal hormone concentrations. In
      addition, stressful situations experienced by the bird mother might affect the
      offspring via reduced amounts of reproductive hormones present in the egg as well
      as available nutrients for the embryo.

PMID- 21886827
TI  - Genetic variants of human granzyme B predict transplant outcomes after HLA
      matched unrelated bone marrow transplantation for myeloid malignancies.
AB  - Serine protease granzyme B plays important roles in infections, autoimmunity,
      transplant rejection, and antitumor immunity. A triple-mutated granzyme B variant
      that encodes three amino substitutions (Q48R, P88A, and Y245H) has been reported
      to have altered biological functions. In the polymorphism rs8192917 (2364A>G),
      the A and G alleles represent wild type QPY and RAH mutant variants,
      respectively. In this study, we analyzed the impact of granzyme B polymorphisms
      on transplant outcomes in recipients undergoing unrelated HLA-fully matched T
      cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow
      Program. The granzyme B genotypes were retrospectively analyzed in a cohort of
      613 pairs of recipients with hematological malignancies and their unrelated
      donors. In patients with myeloid malignancies consisting of acute myeloid
      leukemia and myelodysplastic syndrome, the donor G/G or A/G genotype was
      associated with improved overall survival (OS; adjusted hazard ratio [HR], 0.60;
      95% confidence interval [CI], 0.41-0.89; P = 0.01) as well as transplant related
      mortality (TRM; adjusted HR, 0.48; 95% CI, 0.27-0.86, P = 0.01). The recipient
      G/G or A/G genotype was associated with a better OS (adjusted HR, 0.68; 95% CI,
      0.47-0.99; P = 0.05) and a trend toward a reduced TRM (adjusted HR, 0.61; 95% CI,
      0.35-1.06; P = 0.08). Granzyme B polymorphism did not have any effect on the
      transplant outcomes in patients with lymphoid malignancies consisting of acute
      lymphoid leukemia and malignant lymphoma. These data suggest that there is an
      association between the granzyme B genotype and better clinical outcomes in
      patients with myeloid malignancies after unrelated BMT.

PMID- 21886828
TI  - Characterisation of genome-wide association epistasis signals for serum uric acid
      in human population isolates.
AB  - Genome-wide association (GWA) studies have identified a number of loci underlying
      variation in human serum uric acid (SUA) levels with the SLC2A9 gene having the
      largest effect identified so far. Gene-gene interactions (epistasis) are largely
      unexplored in these GWA studies. We performed a full pair-wise genome scan in the
      Italian MICROS population (n = 1201) to characterise epistasis signals in SUA
      levels. In the resultant epistasis profile, no SNP pairs reached the Bonferroni
      adjusted threshold for the pair-wise genome-wide significance. However, SLC2A9
      was found interacting with multiple loci across the genome, with NFIA-SLC2A9 and
      SLC2A9-ESRRAP2 being significant based on a threshold derived for interactions
      between GWA significant SNPs and the genome and jointly explaining 8.0% of the
      phenotypic variance in SUA levels (3.4% by interaction components). Epistasis
      signal replication in a CROATIAN population (n = 1772) was limited at the SNP
      level but improved dramatically at the gene ontology level. In addition, gene
      ontology terms enriched by the epistasis signals in each population support links
      between SUA levels and neurological disorders. We conclude that GWA epistasis
      analysis is useful despite relatively low power in small isolated populations.

PMID- 21886829
TI  - Metastasis of tumor cells is enhanced by downregulation of Bit1.
AB  - BACKGROUND: Resistance to anoikis, which is defined as apoptosis induced by loss
      of integrin-mediated cell attachment to the extracellular matrix, is a
      determinant of tumor progression and metastasis. We have previously identified
      the mitochondrial Bit1 (Bcl-2 inhibitor of transcription) protein as a novel
      anoikis effector whose apoptotic function is independent from caspases and is
      uniquely controlled by integrins. In this report, we examined the possibility
      that Bit1 is suppressed during tumor progression and that Bit1 downregulation may
      play a role in tumor metastasis. METHODOLOGY/PRINCIPAL FINDINGS: Using a human
      breast tumor tissue array, we found that Bit1 expression is suppressed in a
      significant fraction of advanced stages of breast cancer. Targeted disruption of
      Bit1 via shRNA technology in lowly aggressive MCF7 cells conferred enhanced
      anoikis resistance, adhesive and migratory potential, which correlated with an
      increase in active Extracellular kinase regulated (Erk) levels and a decrease in
      Erk-directed phosphatase activity. These pro-metastasis phenotypes were also
      observed following downregulation of endogenous Bit1 in Hela and B16F1 cancer
      cell lines. The enhanced migratory and adhesive potential of Bit1 knockdown cells
      is in part dependent on their high level of Erk activation since down-regulating
      Erk in these cells attenuated their enhanced motility and adhesive properties.
      The Bit1 knockdown pools also showed a statistically highly significant increase
      in experimental lung metastasis, with no differences in tumor growth relative to
      control clones in vivo using a BALB/c nude mouse model system. Importantly, the
      pulmonary metastases of Bit1 knockdown cells exhibited increased phospho-Erk
      staining. CONCLUSIONS/SIGNIFICANCE: These findings indicate that downregulation
      of Bit1 conferred cancer cells with enhanced anoikis resistance, adhesive and
      migratory properties in vitro and specifically potentiated tumor metastasis in
      vivo. These results underscore the therapeutic importance of restoring Bit1
      expression in cancer cells to circumvent metastasis at least in part through
      inhibition of the Erk pathway.

PMID- 21886830
TI  - Sex-specific dynamics of global chromatin changes in fetal mouse germ cells.
AB  - Mammalian germ cells undergo global reprogramming of DNA methylation during their
      development. Global DNA demethylation occurs around the time when the primordial
      germ cells colonize the embryonic gonads and this coincides with dynamic changes
      in chromatin composition. Global de novo DNA methylation takes place with
      remarkably different dynamics between the two sexes, prospermatogonia attaining
      methylation during fetal stages and oocytes attaining methylation postnatally.
      Our hypothesis was that dynamic changes in chromatin composition may precede or
      accompany the wave of global DNA de novo methylation as well. We used
      immunocytochemistry to measure global DNA methylation and chromatin components in
      male and female mouse fetal germ cells compared to control somatic cells of the
      gonad. We found that global DNA methylation levels sharply increased in male germ
      cells at 17.5 days post coitum, but remained low in female germ cells at all
      fetal stages. Global changes in chromatin composition: i, preceded global DNA
      methylation in fetal germ cells; ii, sex specifically occurred in male but not in
      female germ cells; iii, affected active and repressive histone marks and iv,
      included histone tail and histone globular domain modifications. Our data suggest
      that dynamic changes of chromatin composition may provide a framework for the
      pattern of male-specific de novo DNA methylation in prospermatogonia.

PMID- 21886832
TI  - Hepatitis C virus infection suppresses the interferon response in the liver of
      the human hepatocyte chimeric mouse.
AB  - BACKGROUND AND AIMS: Recent studies indicate that hepatitis C virus (HCV) can
      modulate the expression of various genes including those involved in interferon
      signaling, and up-regulation of interferon-stimulated genes by HCV was reported
      to be strongly associated with treatment outcome. To expand our understanding of
      the molecular mechanism underlying treatment resistance, we analyzed the direct
      effects of interferon and/or HCV infection under immunodeficient conditions using
      cDNA microarray analysis of human hepatocyte chimeric mice. METHODS: Human serum
      containing HCV genotype 1b was injected into human hepatocyte chimeric mice. IFN
      alpha was administered 8 weeks after inoculation, and 6 hours later human
      hepatocytes in the mouse livers were collected for microarray analysis. RESULTS:
      HCV infection induced a more than 3-fold change in the expression of 181 genes,
      especially genes related to Organismal Injury and Abnormalities, such as fibrosis
      or injury of the liver (P = 5.90E-16~3.66E-03). IFN administration induced more
      than 3-fold up-regulation in the expression of 152 genes. Marked induction was
      observed in the anti-fibrotic chemokines such as CXCL9, suggesting that IFN
      treatment might lead not only to HCV eradication but also prevention and repair
      of liver fibrosis. HCV infection appeared to suppress interferon signaling via
      significant reduction in interferon-induced gene expression in several genes of
      the IFN signaling pathway, including Mx1, STAT1, and several members of the CXCL
      and IFI families (P = 6.0E-12). Genes associated with Antimicrobial Response and
      Inflammatory Response were also significantly repressed (P = 5.22*10(
      10)~1.95*10(-2)). CONCLUSIONS: These results provide molecular insights into
      possible mechanisms used by HCV to evade innate immune responses, as well as
      novel therapeutic targets and a potential new indication for interferon therapy.

PMID- 21886831
TI  - Down-regulated NOD2 by immunosuppressants in peripheral blood cells in patients
      with SLE reduces the muramyl dipeptide-induced IL-10 production.
AB  - BACKGROUND: Pattern recognition receptors (PRRs) such as Toll-like receptors are
      aberrantly expressed of peripheral blood mononuclear cells (PBMCs) in systemic
      lupus erythematosus (SLE) patients, for playing immunopathological roles.
      METHODOLOGY/PRINCIPAL FINDINGS: We investigated the expression and function of
      the PRR nucleotide-binding oligomerization domain (NOD2) in SLE. NOD2 expression
      in T, B lymphocytes, monocytes, myeloid dendritic cells (mDCs) and plasmacytoid
      dendritic cells (pDCs) was assessed in SLE patients and healthy controls (HCs)
      using flow cytometric analysis. Ex vivo production of cytokines from PBMCs upon
      NOD2 agonist muramyl dipeptide (MDP) stimulation was assessed using Cytometric
      Bead Array. Over-expression of NOD2 in monocytes was observed in
      immunosuppressant naive SLE patients, and was positively associated with longer
      disease duration. Immunosuppressive therapy was an independent explanatory
      variable for downregulating NOD2 expression in CD8+ T, monocytes, mDCs and pDCs.
      Ex vivo basal productions of cytokines (IL-6, IL-8 and IL-10) were significantly
      increased in immunosuppressant naive patients and patients with active disease
      despite immunosuppressants compared with HCs. Upon MDP stimulaiton, relative
      induction (%) of cytokines (IL-1beta) from PBMC was significantly increased in
      immunosuppressant naive patients with inactive disease, and patients with active
      disease despite immunosuppressant treatment compared with HCs. Immunosuppressant
      usage was associated with a decreased basal production and MDP induced relative
      induction (%) of IL-10 in patients with inactive disease compared with
      immunosuppressant naive patients and HCs. CONCLUSIONS/SIGNIFICANCE: Bacterial
      exposure may increase the NOD2 expression in monocytes in immunosuppressant naive
      SLE patients which can subsequently lead to aberrant activation of PBMCs to
      produce proinflammatory cytokines, implicating the innate immune response for
      extracellular pathogens in the immunopathological mechanisms in SLE.
      Immunosuppressant therapy may downregulate NOD2 expression in CD8+ T lymphocytes,
      monocytes, and DCs in SLE patients which subsequently IL-10 reduction,
      contributing towards the regulation of immunopathological mechanisms of SLE, at
      the expense of increasing risk of bacterial infection.

PMID- 21886834
TI  - Structural and dynamical patterns on online social networks: the Spanish May 15th
      movement as a case study.
AB  - The number of people using online social networks in their everyday life is
      continuously growing at a pace never saw before. This new kind of communication
      has an enormous impact on opinions, cultural trends, information spreading and
      even in the commercial success of new products. More importantly, social online
      networks have revealed as a fundamental organizing mechanism in recent country
      wide social movements. In this paper, we provide a quantitative analysis of the
      structural and dynamical patterns emerging from the activity of an online social
      network around the ongoing May 15th (15M) movement in Spain. Our network is made
      up by users that exchanged tweets in a time period of one month, which includes
      the birth and stabilization of the 15M movement. We characterize in depth the
      growth of such dynamical network and find that it is scale-free with communities
      at the mesoscale. We also find that its dynamics exhibits typical features of
      critical systems such as robustness and power-law distributions for several
      quantities. Remarkably, we report that the patterns characterizing the spreading
      dynamics are asymmetric, giving rise to a clear distinction between information
      sources and sinks. Our study represents a first step towards the use of data from
      online social media to comprehend modern societal dynamics.

PMID- 21886833
TI  - Mapping functional brain activation using [14C]-iodoantipyrine in male serotonin
      transporter knockout mice.
AB  - BACKGROUND: Serotonin transporter knockout mice have been a powerful tool in
      understanding the role played by the serotonin transporter in modulating
      physiological function and behavior. However, little work has examined brain
      function in this mouse model. We tested the hypothesis that male knockout mice
      show exaggerated limbic activation during exposure to an emotional stressor,
      similar to human subjects with genetically reduced transcription of the serotonin
      transporter. METHODOLOGY/PRINCIPAL FINDINGS: Functional brain mapping using
      [(14)C]-iodoantipyrine was performed during recall of a fear conditioned tone.
      Regional cerebral blood flow was analyzed by statistical parametric mapping from
      autoradiographs of the three-dimensionally reconstructed brains. During recall,
      knockout mice compared to wild-type mice showed increased freezing, increased
      regional cerebral blood flow of the amygdala, insula, and barrel field
      somatosensory cortex, decreased regional cerebral blood flow of the ventral
      hippocampus, and conditioning-dependent alterations in regional cerebral blood
      flow in the medial prefrontal cortex (prelimbic, infralimbic, and cingulate).
      Anxiety tests relying on sensorimotor exploration showed a small (open field) or
      paradoxical effect (marble burying) of loss of the serotonin transporter on
      anxiety behavior, which may reflect known abnormalities in the knockout animal's
      sensory system. Experiments evaluating whisker function showed that knockout mice
      displayed impaired whisker sensation in the spontaneous gap crossing task and
      appetitive gap cross training. CONCLUSIONS: This study is the first to
      demonstrate altered functional activation in the serotonin transporter knockout
      mice of critical nodes of the fear conditioning circuit. Alterations in whisker
      sensation and functional activation of barrel field somatosensory cortex extend
      earlier reports of barrel field abnormalities, which may confound behavioral
      measures relying on sensorimotor exploration.

PMID- 21886835
TI  - Modeling two-oscillator circadian systems entrained by two environmental cycles.
AB  - Several experimental studies have altered the phase relationship between photic
      and non-photic environmental, 24 h cycles (zeitgebers) in order to assess their
      role in the synchronization of circadian rhythms. To assist in the interpretation
      of the complex activity patterns that emerge from these "conflicting zeitgeber"
      protocols, we present computer simulations of coupled circadian oscillators
      forced by two independent zeitgebers. This circadian system configuration was
      first employed by Pittendrigh and Bruce (1959), to model their studies of the
      light and temperature entrainment of the eclosion oscillator in Drosophila.
      Whereas most of the recent experiments have restricted conflicting zeitgeber
      experiments to two experimental conditions, by comparing circadian oscillator
      phases under two distinct phase relationships between zeitgebers (usually 0 and
      12 h), Pittendrigh and Bruce compared eclosion phase under 12 distinct phase
      relationships, spanning the 24 h interval. Our simulations using non-linear
      differential equations replicated complex non-linear phenomena, such as "phase
      jumps" and sudden switches in zeitgeber preferences, which had previously been
      difficult to interpret. Our simulations reveal that these phenomena generally
      arise when inter-oscillator coupling is high in relation to the zeitgeber
      strength. Manipulations in the structural symmetry of the model indicated that
      these results can be expected to apply to a wide range of system configurations.
      Finally, our studies recommend the use of the complete protocol employed by
      Pittendrigh and Bruce, because different system configurations can generate
      similar results when a "conflicting zeitgeber experiment" incorporates only two
      phase relationships between zeitgebers.

PMID- 21886836
TI  - Arabidopsis ovate family proteins, a novel transcriptional repressor family,
      control multiple aspects of plant growth and development.
AB  - BACKGROUND: The Arabidopsis genome contains 18 genes that are predicted to encode
      Ovate Family Proteins (AtOFPs), a protein family characterized by a conserved
      OVATE domain, an approximately 70-amino acid domain that was originally found in
      tomato OVATE protein. Among AtOFP family members, AtOFP1 has been shown to
      suppress cell elongation, in part, by suppressing the expression of AtGA20ox1,
      AtOFP4 has been shown to regulate secondary cell wall formation by interact with
      KNOTTED1-LIKE HOMEODOMAIN PROTEIN 7 (KNAT7), and AtOFP5 has been shown to
      regulate the activity of a BEL1-LIKEHOMEODOMAIN 1(BLH1)-KNAT3 complex during
      early embryo sac development, but little is known about the function of other
      AtOFPs. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated here that AtOFP proteins
      could function as effective transcriptional repressors in the Arabidopsis
      protoplast transient expression system. The analysis of loss-of-function alleles
      of AtOFPs suggested AtOFP genes may have overlapping function in regulating plant
      growth and development, because none of the single mutants identified, including
      T-DNA insertion mutants in AtOFP1, AtOFP4, AtOFP8, AtOFP10, AtOFP15 and AtOFP16,
      displayed any apparent morphological defects. Further, Atofp1 Atofp4 and Atofp15
      Atofp16 double mutants still did not differ significantly from wild-type. On the
      other hand, plants overexpressing AtOFP genes displayed a number of abnormal
      phenotypes, which could be categorized into three distinct classes, suggesting
      that AtOFP genes may also have diverse functions in regulating plant growth and
      development. Further analysis suggested that AtOFP1 regulates cotyledon
      development in a postembryonic manner, and global transcript profiling revealed
      that it suppress the expression of many other genes. CONCLUSIONS/SIGNIFICANCE:
      Our results showed that AtOFPs function as transcriptional repressors and they
      regulate multiple aspects of plant growth and development. These results provided
      the first overview of a previously unknown transcriptional repressor family, and
      revealed their possible roles in plant growth and development.

PMID- 21886837
TI  - B cell signature during inactive systemic lupus is heterogeneous: toward a
      biological dissection of lupus.
AB  - Systemic lupus erythematosous (SLE) is an autoimmune disease with an important
      clinical and biological heterogeneity. B lymphocytes appear central to the
      development of SLE which is characterized by the production of a large variety of
      autoantibodies and hypergammaglobulinemia. In mice, immature B cells from
      spontaneous lupus prone animals are able to produce autoantibodies when
      transferred into immunodeficient mice, strongly suggesting the existence of
      intrinsic B cell defects during lupus. In order to approach these defects in
      humans, we compared the peripheral B cell transcriptomas of quiescent lupus
      patients to normal B cell transcriptomas. When the statistical analysis is
      performed on the entire group of patients, the differences between patients and
      controls appear quite weak with only 14 mRNA genes having a false discovery rate
      ranging between 11 and 17%, with 6 underexpressed genes (PMEPA1, TLR10, TRAF3IP2,
      LDOC1L, CD1C and EGR1). However, unforced hierarchical clustering of the
      microarrays reveals a subgroup of lupus patients distinct from both the controls
      and the other lupus patients. This subgroup has no detectable clinical or
      immunological phenotypic peculiarity compared to the other patients, but is
      characterized by 1/an IL-4 signature and 2/the abnormal expression of a large set
      of genes with an extremely low false discovery rate, mainly pointing to the
      biological function of the endoplasmic reticulum, and more precisely to genes
      implicated in the Unfolded Protein Response, suggesting that B cells entered an
      incomplete BLIMP1 dependent plasmacytic differentiation which was undetectable by
      immunophenotyping. Thus, this microarray analysis of B cells during quiescent
      lupus suggests that, despite a similar lupus phenotype, different biological
      roads can lead to human lupus.

PMID- 21886838
TI  - Calcineurin inhibitor-induced and Ras-mediated overexpression of VEGF in renal
      cancer cells involves mTOR through the regulation of PRAS40.
AB  - Malignancy is a major problem in patients treated with immunosuppressive agents.
      We have demonstrated that treatment with calcineurin inhibitors (CNIs) can induce
      the activation of proto-oncogenic Ras, and may promote a rapid progression of
      human renal cancer through the overexpression of vascular endothelial growth
      factor (VEGF). Interestingly, we found that CNI-induced VEGF overexpression and
      cancer cell proliferation was inhibited by rapamycin treatment, indicating
      potential involvement of the mammalian target of rapamycin (mTOR) pathway in this
      tumorigenic process. Here, we examined the role of mTOR pathway in mediating CNI-
      and Ras-induced overexpression of VEGF in human renal cancer cells (786-0 and
      Caki-1). We found that the knockdown of raptor (using siRNA) significantly
      decreased CNI-induced VEGF promoter activity as observed by promoter-luciferase
      assay, suggesting the role of mTOR complex1 (mTORC1) in CNI-induced VEGF
      transcription. It is known that mTOR becomes activated following phosphorylation
      of its negative regulator PRAS40, which is a part of mTORC1. We observed that CNI
      treatment and activation of H-Ras (through transfection of an active H-Ras
      plasmid) markedly increased the phosphorylation of PRAS40, and the transfection
      of cells using a dominant-negative plasmid of Ras, significantly decreased PRAS40
      phosphorylation. Protein kinase C (PKC)-zeta and PKC-delta, which are critical
      intermediary signaling molecules for CNI-induced tumorigenic pathway, formed
      complex with PRAS40; and we found that the CNI treatment increased the complex
      formation between PRAS40 and PKC, particularly (PKC)-zeta. Inhibition of PKC
      activity using pharmacological inhibitor markedly decreased H-Ras-induced
      phosphorylation of PRAS40. The overexpression of PRAS40 in renal cancer cells
      significantly down-regulated CNI- and H-Ras-induced VEGF transcriptional
      activation. Finally, it was observed that CNI treatment increased the expression
      of phosho-PRAS40 in renal tumor tissues in vivo. Together, the phosphorylation of
      PRAS40 is critical for the activation of mTOR in CNI-induced VEGF overexpression
      and renal cancer progression.

PMID- 21886839
TI  - FrzS regulates social motility in Myxococcus xanthus by controlling
      exopolysaccharide production.
AB  - Myxococcus xanthus Social (S) motility occurs at high cell densities and is
      powered by the extension and retraction of Type IV pili which bind ligands
      normally found in matrix exopolysaccharides (EPS). Previous studies showed that
      FrzS, a protein required for S-motility, is organized in polar clusters that show
      pole-to-pole translocation as cells reverse their direction of movement. Since
      the leading cell pole is the site of both the major FrzS cluster and type IV
      pilus extension/retraction, it was suggested that FrzS might regulate S-motility
      by activating pili at the leading cell pole. Here, we show that FrzS regulates
      EPS production, rather than type IV pilus function. We found that the frzS
      phenotype is distinct from that of Type IV pilus mutants such as pilA and pilT,
      but indistinguishable from EPS mutants, such as epsZ. Indeed, frzS mutants can be
      rescued by the addition of purified EPS, 1% methylcellulose, or co-culturing with
      wildtype cells. Our data also indicate that the cell density requirement in S
      motility is likely a function of the ability of cells to construct functional
      multicellular clusters surrounding an EPS core.

PMID- 21886840
TI  - Lymphoid organ-resident dendritic cells exhibit unique transcriptional
      fingerprints based on subset and site.
AB  - Lymphoid organ-resident DC subsets are thought to play unique roles in
      determining the fate of T cell responses. Recent studies focusing on a single
      lymphoid organ identified molecular pathways that are differentially operative in
      each DC subset and led to the assumption that a given DC subset would more or
      less exhibit the same genomic and functional profiles throughout the body.
      Whether the local milieu in different anatomical sites can also influence the
      transcriptome of DC subsets has remained largely unexplored. Here, we
      interrogated the transcriptional relationships between lymphoid organ-resident DC
      subsets from spleen, gut- and skin-draining lymph nodes, and thymus of C57BL/6
      mice. For this purpose, major resident DC subsets including CD4 and CD8 DCs were
      sorted at high purity and gene expression profiles were compared using microarray
      analysis. This investigation revealed that lymphoid organ-resident DC subsets
      exhibit divergent genomic programs across lymphoid organs. Interestingly, we also
      found that transcriptional and biochemical properties of a given DC subset can
      differ between lymphoid organs for lymphoid organ-resident DC subsets, but not
      plasmacytoid DCs, suggesting that determinants of the tissue milieu program
      resident DCs for essential site-specific functions.

PMID- 21886841
TI  - Myc localizes to histone locus bodies during replication in Drosophila.
AB  - Myc is an important protein at the center of multiple pathways required for
      growth and proliferation in animals. The absence of Myc is lethal in flies and
      mice, and its over-production is a potent inducer of over-proliferation and
      cancer. Myc protein is localized to the nucleus where it executes its many
      functions, however the specific sub-nuclear localization of Myc has rarely been
      reported. The work we describe here began with an observation of unexpected,
      punctate spots of Myc protein in certain regions of Drosophila embryos. We
      investigated the identity of these puncta and demonstrate that Myc is co
      localized with coilin, a marker for sub-nuclear organelles known as Cajal Bodies
      (CBs), in embryos, larvae and ovaries. Using antibodies specific for U7 snRNP
      component Lsm11, we show that the majority of Myc and coilin co-localization
      occurs in Histone Locus Bodies (HLBs), the sites of histone mRNA transcription
      and processing. Furthermore, Myc localizes to HLBs only during replication in
      mitotic and endocycling cells, suggesting that its role there relates to
      replication-dependent canonical histone gene transcription. These results provide
      evidence that sub-nuclear localization of Myc is cell-cycle dependent and
      potentially important for histone mRNA production and processing.

PMID- 21886842
TI  - Air trapping on chest CT is associated with worse ventilation distribution in
      infants with cystic fibrosis diagnosed following newborn screening.
AB  - BACKGROUND: In school-aged children with cystic fibrosis (CF) structural lung
      damage assessed using chest CT is associated with abnormal ventilation
      distribution. The primary objective of this analysis was to determine the
      relationships between ventilation distribution outcomes and the presence and
      extent of structural damage as assessed by chest CT in infants and young children
      with CF. METHODS: Data of infants and young children with CF diagnosed following
      newborn screening consecutively reviewed between August 2005 and December 2009
      were analysed. Ventilation distribution (lung clearance index and the first and
      second moment ratios [LCI, M(1)/M(0) and M(2)/M(0), respectively]), chest CT and
      airway pathology from bronchoalveolar lavage were determined at diagnosis and
      then annually. The chest CT scans were evaluated for the presence or absence of
      bronchiectasis and air trapping. RESULTS: Matched lung function, chest CT and
      pathology outcomes were available in 49 infants (31 male) with bronchiectasis and
      air trapping present in 13 (27%) and 24 (49%) infants, respectively. The presence
      of bronchiectasis or air trapping was associated with increased M(2)/M(0) but not
      LCI or M(1)/M(0). There was a weak, but statistically significant association
      between the extent of air trapping and all ventilation distribution outcomes.
      CONCLUSION: These findings suggest that in early CF lung disease there are weak
      associations between ventilation distribution and lung damage from chest CT.
      These finding are in contrast to those reported in older children. These findings
      suggest that assessments of LCI could not be used to replace a chest CT scan for
      the assessment of structural lung disease in the first two years of life. Further
      research in which both MBW and chest CT outcomes are obtained is required to
      assess the role of ventilation distribution in tracking the progression of lung
      damage in infants with CF.

PMID- 21886843
TI  - Circulating microRNAs in patients with chronic hepatitis C and non-alcoholic
      fatty liver disease.
AB  - MicroRNAs miR-122, miR-34a, miR-16 and miR-21 are commonly deregulated in liver
      fibrosis and hepatocellular carcinoma. This study examined whether circulating
      levels of these miRNAs correlate with hepatic histological disease severity in
      patients with chronic hepatitis C infection (CHC) or non-alcoholic fatty-liver
      disease (NAFLD) and can potentially serve as circulating markers for disease
      stage assessment. We first used an in vitro model of hepatitis C virus (HCV)
      infection to measure the extracellular levels of these four miRNAs. Whereas miR
      21 extracellular levels were unchanged, extracellular levels of miR-122, miR-34a
      and to a lesser extent miR-16, steadily increased during the course of HCV
      infection, independently of viral replication and production. Similarly, in CHC
      patients, serum levels of miR-122, miR-34a and miR-16 were significantly higher
      than in control individuals, while miR-21 levels were unchanged. There was no
      correlation between the serum levels of any of these microRNAs and HCV viral
      loads. In contrast, miR-122 and miR-34a levels positively correlated with disease
      severity. Identical results were obtained in an independent cohort of CHC
      patients. We extended the study to patients with NAFLD. As observed in CHC
      patients, serum levels of miR-122, miR-34a and miR-16 were significantly higher
      in NAFLD patients than in controls, while miR-21 levels were unchanged. Again,
      miR-122 and miR-34a levels positively correlated with disease severity from
      simple steatosis to steatohepatitis. In both CHC and NAFLD patient groups, serum
      levels of miR-122 and miR-34a correlated with liver enzymes levels, fibrosis
      stage and inflammation activity. miR-122 levels also correlated with serum lipids
      in NAFLD patients. CONCLUSION: Serum levels of miR-34a and miR-122 may represent
      novel, noninvasive biomarkers of diagnosis and histological disease severity in
      patients with CHC or NAFLD.

PMID- 21886844
TI  - Improved immunodetection of endogenous alpha-synuclein.
AB  - alpha-Synuclein is a key molecule in understanding the pathogenesis of
      neurodegenerative alpha-synucleinopathies such as Parkinson's disease. Despite
      extensive research, however, its precise function remains unclear partly because
      of a difficulty in immunoblotting detection of endogenous alpha-synuclein. This
      difficulty has largely restricted the progress for alpha-synucleinopathy
      research. Here, we report that alpha-synuclein monomers tend to easily detach
      from blotted membranes, resulting in no or very poor detection. To prevent this
      detachment, a mild fixation of blotted membranes with paraformaldehyde was
      applied to the immunoblotting method. Amazingly, this fixation led to clear and
      strong detection of endogenous alpha-synuclein, which has been undetectable by a
      conventional immunoblotting method. Specifically, we were able to detect
      endogenous alpha-synuclein in various human cell lines, including SH-SY5Y,
      HEK293, HL60, HeLa, K562, A375, and Daoy, and a mouse cell line B16 as well as in
      several mouse tissues such as the spleen and kidney. Moreover, it should be noted
      that we could clearly detect endogenous alpha-synuclein phosphorylated at Ser-129
      in several human cell lines. Thus, in some tissues and cultured cells, endogenous
      alpha-synuclein becomes easily detectable by simply fixing the blotted membranes.
      This improved immunoblotting method will allow us to detect previously
      undetectable endogenous alpha-synuclein, thereby facilitating alpha-synuclein
      research.

PMID- 21886845
TI  - One carbon metabolism in SAR11 pelagic marine bacteria.
AB  - The SAR11 Alphaproteobacteria are the most abundant heterotrophs in the oceans
      and are believed to play a major role in mineralizing marine dissolved organic
      carbon. Their genomes are among the smallest known for free-living heterotrophic
      cells, raising questions about how they successfully utilize complex organic
      matter with a limited metabolic repertoire. Here we show that conserved genes in
      SAR11 subgroup Ia (Candidatus Pelagibacter ubique) genomes encode pathways for
      the oxidation of a variety of one-carbon compounds and methyl functional groups
      from methylated compounds. These pathways were predicted to produce energy by
      tetrahydrofolate (THF)-mediated oxidation, but not to support the net
      assimilation of biomass from C1 compounds. Measurements of cellular ATP content
      and the oxidation of (14)C-labeled compounds to (14)CO(2) indicated that
      methanol, formaldehyde, methylamine, and methyl groups from glycine betaine
      (GBT), trimethylamine (TMA), trimethylamine N-oxide (TMAO), and
      dimethylsulfoniopropionate (DMSP) were oxidized by axenic cultures of the SAR11
      strain Ca. P. ubique HTCC1062. Analyses of metagenomic data showed that genes for
      C1 metabolism occur at a high frequency in natural SAR11 populations. In short
      term incubations, natural communities of Sargasso Sea microbial plankton
      expressed a potential for the oxidation of (14)C-labeled formate, formaldehyde,
      methanol and TMAO that was similar to cultured SAR11 cells and, like cultured
      SAR11 cells, incorporated a much larger percentage of pyruvate and glucose (27
      35%) than of C1 compounds (2-6%) into biomass. Collectively, these genomic,
      cellular and environmental data show a surprising capacity for demethylation and
      C1 oxidation in SAR11 cultures and in natural microbial communities dominated by
      SAR11, and support the conclusion that C1 oxidation might be a significant
      conduit by which dissolved organic carbon is recycled to CO(2) in the upper
      ocean.

PMID- 21886846
TI  - Co-regulation of histone-modifying enzymes in cancer.
AB  - Cancer is characterized by aberrant patterns of expression of multiple genes.
      These major shifts in gene expression are believed to be due to not only genetic
      but also epigenetic changes. The epigenetic changes are communicated through
      chemical modifications, including histone modifications. However, it is unclear
      whether the binding of histone-modifying proteins to genomic regions and the
      placing of histone modifications efficiently discriminates corresponding genes
      from the rest of the genes in the human genome. We performed gene expression
      analysis of histone demethylases (HDMs) and histone methyltransferases (HMTs),
      their target genes and genes with relevant histone modifications in normal and
      tumor tissues. Surprisingly, this analysis revealed the existence of correlations
      in the expression levels of different HDMs and HMTs. The observed HDM/HMT gene
      expression signature was specific to particular normal and cancer cell types and
      highly correlated with target gene expression and the expression of genes with
      histone modifications. Notably, we observed that trimethylation at lysine 4 and
      lysine 27 separated preferentially expressed and underexpressed genes, which was
      strikingly different in cancer cells compared to normal cells. We conclude that
      changes in coordinated regulation of enzymes executing histone modifications may
      underlie global epigenetic changes occurring in cancer.

PMID- 21886847
TI  - Genetic variants in MARCO are associated with the susceptibility to pulmonary
      tuberculosis in Chinese Han population.
AB  - BACKGROUND: Susceptibility to tuberculosis is not only determined by
      Mycobacterium tuberculosis infection, but also by the genetic component of the
      host. Macrophage receptor with a collagenous structure (MARCO) is essential
      components required for toll like receptor-signaling in macrophage response to
      Mycobacterium tuberculosis, which may contribute to tuberculosis risk. PRINCIPAL
      FINDINGS: To specifically investigated whether single nucleotide polymorphisms
      (SNPs) in MARCO gene are associated with pulmonary tuberculosis in Chinese Han
      population. By selecting tagging SNPs in MARCO gene, 17 tag SNPs were identified
      and genotyped in 923 pulmonary tuberculosis patients and 1033 healthy control
      subjects using a hospital based case-control association study. Single-point and
      haplotype analysis revealed an association in intron and exon region of MARCO
      gene. One SNP (rs17009726) was associated with susceptibility to pulmonary
      tuberculosis, where the carriers of the G allele had a 1.65 fold (95% CI = 1.32
      2.05, p(corrected) = 9.27E-5) increased risk of pulmonary tuberculosis. Haplotype
      analysis revealed that haplotype GC containing G allele of 17009726 and haplotype
      TGCC (rs17795618T/A, rs1371562G/T, rs6761637T/C, rs2011839C/T) were also
      associated with susceptibility to pulmonary tuberculosis (p(corrected) = 0.0001
      and 0.029, respectively). CONCLUSIONS: Our study suggested that genetic variants
      in MARCO gene were associated with pulmonary tuberculosis susceptibility in
      Chinese Han population, and the findings emphasize the importance of MARCO
      mediated immune responses in the pathogenesis of tuberculosis.

PMID- 21886848
TI  - The value of educational messages embedded in a community-based approach to
      combat dengue Fever: a systematic review and meta regression analysis.
AB  - BACKGROUND: The effects of various dengue control measures have been investigated
      in previous studies. The aim of this review was to investigate the relative
      effectiveness (RE) of different educational messages embedded in a community
      based approach on the incidence of Aedes aegypti larvae using entomological
      measures as outcomes. METHODS AND FINDINGS: A systematic electronic search using
      Medline, Embase, Web of Science and the Cochrane Library was carried out to March
      2010. Previous systematic reviews were also assessed. Data concerning
      interventions, outcomes, effect size and study design were extracted. Basic meta
      analyses were done for pooled effect size, heterogeneity and publication bias
      using Comprehensive Meta-analysis. Further analysis of heterogeneitity was done
      by multi-level modelling using MLwiN. 21 publications with 22 separate studies
      were included in this review. Meta-analysis of these 22 pooled studies showed an
      RE of 0.25 (95% CI 0.17-0.37), but with substantial heterogeneity (Cochran's Q  =
      1254, df  =  21, p  =  < 0.001,). Further analysis of this heterogeneity showed
      that over 60% of between study variance could be explained by just two variables;
      whether or not studies used historic or contemporary controls and time from
      intervention to assessment. When analyses were restricted to those studies using
      contemporary control, there was a polynomial relationship between effectiveness
      and time to assessment. Whether or not chemicals or other control measures were
      used did not appear have any effect on intervention effectiveness. CONCLUSION:
      The results suggest that such measures do appear to be effective at reducing
      entomological indices. However, those studies that use historical controls almost
      certainly overestimate the value of interventions. There is evidence that
      interventions are most effective some 18 to 24 months after the intervention but
      then subsequently decline.

PMID- 21886849
TI  - Genetic diversity and population structure of the secondary symbiont of tsetse
      flies, Sodalis glossinidius, in sleeping sickness foci in Cameroon.
AB  - BACKGROUND: Previous studies have shown substantial differences in Sodalis
      glossinidius and trypanosome infection rates between Glossina palpalis palpalis
      populations from two Cameroonian foci of human African trypanosomiasis (HAT),
      Bipindi and Campo. We hypothesized that the geographical isolation of the two
      foci may have induced independent evolution in the two areas, resulting in the
      diversification of symbiont genotypes. METHODOLOGY/PRINCIPAL FINDINGS: To test
      this hypothesis, we investigated the symbiont genetic structure using the allelic
      size variation at four specific microsatellite loci. Classical analysis of
      molecular variance (AMOVA) and differentiation statistics revealed that most of
      the genetic diversity was observed among individuals within populations and
      frequent haplotypes were shared between populations. The structure of genetic
      diversity varied at different geographical scales, with almost no differentiation
      within the Campo HAT focus and a low but significant differentiation between the
      Campo and Bipindi HAT foci. CONCLUSIONS/SIGNIFICANCE: The data provided new
      information on the genetic diversity of the secondary symbiont population
      revealing mild structuring. Possible interactions between S. glossinidius
      subpopulations and Glossina species that could favor tsetse fly infections by a
      given trypanosome species should be further investigated.

PMID- 21886850
TI  - Dextran fractional clearance studies in acute dengue infection.
AB  - BACKGROUND: Although increased capillary permeability is the major clinical
      feature associated with severe dengue infections the mechanisms underlying this
      phenomenon remain unclear. Dextran clearance methodology has been used to
      investigate the molecular sieving properties of the microvasculature in clinical
      situations associated with altered permeability, including during pregnancy and
      in various renal disorders. In order to better understand the characteristics of
      the vascular leak associated with dengue we undertook formal dextran clearance
      studies in Vietnamese dengue patients and healthy volunteers.
      METHODOLOGY/PRINCIPAL FINDINGS: We carried out serial clearance studies in 15
      young adult males with acute dengue and evidence of vascular leakage a) during
      the phase of maximal leakage and b) one and three months later, as well as in 16
      healthy control subjects. Interestingly we found no difference in the clearance
      profiles of neutral dextran solutions among the dengue patients at any time-point
      or in comparison to the healthy volunteers. CONCLUSIONS/SIGNIFICANCE: The surface
      glycocalyx layer, a fibre-matrix of proteoglycans, glycosaminoglycans, and plasma
      proteins, forms a complex with the underlying endothelial cells to regulate
      plasma volume within circumscribed limits. It is likely that during dengue
      infections loss of plasma proteins from this layer alters the permeability
      characteristics of the complex; physical and/or electrostatic interactions
      between the dextran molecules and the glycocalyx structure may temporarily
      restore normal function, rendering the technique unsuitable for assessing
      permeability in these patients. The implications for resuscitation of patients
      with dengue shock syndrome (DSS) are potentially important. It is possible that
      continuous low-dose infusions of dextran may help to stabilize the permeability
      barrier in patients with profound or refractory shock, reducing the need for
      repeated boluses, limiting the total colloid volume required. Formal clinical
      studies should help to assess this strategy as an alternative to conventional
      fluid resuscitation for severe DSS.

PMID- 21886851
TI  - The impact of a filariasis control program on Lihir Island, Papua New Guinea.
AB  - BACKGROUND: Annual mass drug administration (MDA) over five years is the WHO's
      recommended strategy to eliminate lymphatic filariasis (LF). Some experts,
      however, consider that longer periods of treatment might be necessary in certain
      high prevalence and transmission environments based upon past unsuccessful field
      experience and modelling. METHODOLOGY/PRINCIPAL FINDINGS: To evaluate predictors
      of success in a LF control program we conducted an ecological study during a pre
      existing MDA program. We studied 27 villages in Lihir Island, Papua New Guinea,
      from two areas with different infection rates before MDA. We undertook surveys to
      collect information on variables potentially having an influence on the outcome
      of the program, including epidemiological (baseline prevalence of infection,
      immigration rate), entomological (vector density) and operational (treatment
      coverage, vector control strategies) variables. The success in a village was
      defined using variables related to the infection (circulating filarial
      antigenemia prevalence < 1%) and transmission (antigenemia prevalence < 1 in 1000
      children born since start of MDA). 8709 people were involved in the MDA program
      and average coverage rates were around 70%. The overall prevalence of filariasis
      fell from an initial 17.91% to 3.76% at round 5 (p < 0.001). Viewed on a village
      by village basis, 12/27 (44%) villages achieved success. In multivariate
      analysis, low baseline prevalence was the only factor predicting both success in
      reducing infection rates (OR 19,26; CI 95% 1,12 to 331,82) and success in
      preventing new infections (OR 27,44; CI 95% 1,05 to 719,6). Low vector density
      and the use of an optimal vector control strategy were also associated with
      success in reducing infection rates, but this did not reach statistical
      significance. CONCLUSIONS/SIGNIFICANCE: Our results provide the data that
      supports the recommendation that high endemic areas may require longer duration
      MDA programs, or alternative control strategies.

PMID- 21886852
TI  - Infection parameters in the sand fly vector that predict transmission of
      Leishmania major.
AB  - To identify parameters of Leishmania infection within a population of infected
      sand flies that reliably predict subsequent transmission to the mammalian host,
      we sampled groups of infected flies and compared infection intensity and degree
      of metacyclogenesis with the frequency of transmission. The percentage of
      parasites within the midgut that were metacyclic promastigotes had the highest
      correlation with the frequency of transmission. Meta-analysis of multiple
      transmission experiments allowed us to establish a percent-metacyclic "cutoff"
      value that predicted transmission competence. Sand fly infections initiated with
      variable doses of parasites resulted in correspondingly altered percentages of
      metacyclic promastigotes, resulting in altered transmission frequency and disease
      severity. Lastly, alteration of sand fly oviposition status and environmental
      conditions at the time of transmission also influenced transmission frequency.
      These observations have implications for transmission of Leishmania by the sand
      fly vector in both the laboratory and in nature, including how the number of
      organisms acquired by the sand fly from an infection reservoir may influence the
      clinical outcome of infection following transmission by bite.

PMID- 21886853
TI  - Diagnosis, clinical features, and self-reported morbidity of Strongyloides
      stercoralis and hookworm infection in a Co-endemic setting.
AB  - BACKGROUND: Infections with Strongyloides stercoralis and other helminths
      represent important, yet often neglected issues in developing countries. Indeed,
      strongyloidiasis can be fatal, but only a few studies provide information
      regarding its health relevance in Africa. Moreover, clinical data on
      symptomatology and typical recognition patterns mainly originate from Western
      travel clinics. METHODOLOGY: A cross-sectional epidemiological survey was carried
      out in a rural part of south-central Cote d'Ivoire. Stool samples from 292
      randomly selected individuals were examined for intestinal helminths, using a
      suite of diagnostic techniques (i.e., Kato-Katz, Baermann funnel, and Koga agar
      plate). Participants were interviewed with a pre-tested questionnaire and
      clinically examined. Multivariate logistic regression analysis was done to relate
      perceived morbidity and clinical findings to helminth infection status. PRINCIPAL
      FINDINGS: The prevalence of hookworm and S. stercoralis was 51.0% and 12.7%,
      respectively. Both infections were strongly associated with each other (adjusted
      odds ratio, 6.73; P < 0.001) and higher prevalences were observed with age. S.
      stercoralis-infected individuals expressed self-reported morbidity considerably
      more often than those with hookworm infection. Clinical examination identified
      high prevalences of various pathologies and detected tendencies to worse health
      conditions in helminth-infected subjects. CONCLUSIONS/SIGNIFICANCE: The use of
      multiple diagnostic tools showed that S. stercoralis and hookworm are co-endemic
      in rural Cote d'Ivoire and that each infection causes clinical symptoms and
      sequelae. Our findings are important for (re-)estimating the burden of helminth
      infections, and highlight the need for integrating epidemiological surveys,
      rigorous diagnostic approaches, and clinical assessments in the developing world.

PMID- 21886854
TI  - Increased CD4+/CD8+ double-positive T cells in chronic Chagasic patients.
AB  - BACKGROUND: CD4+/CD8+ double positive (DP) T cells have been described in healthy
      individuals as well as in patients with autoimmune and chronic infectious
      diseases. In chronic viral infections, this cell subset has effector memory
      phenotype and displays antigen specificity. No previous studies of double
      positive T cells in parasite infections have been carried out.
      METHODOLOGY/PRINCIPAL FINDINGS: Seventeen chronic chagasic patients (7
      asymptomatic and 10 symptomatic) and 24 non-infected donors, including 12 healthy
      and 12 with non-chagasic cardiomyopathy donors were analyzed. Peripheral blood
      was stained for CD3, CD4, CD8, HLA-DR and CD38, and lymphocytes for intracellular
      perforin. Antigen specificity was assessed using HLA*A2 tetramers loaded with T.
      cruzi K1 or influenza virus epitopes. Surface expression of CD107 and
      intracellular IFN-gamma production were determined in K1-specific DP T cells from
      11 chagasic donors. Heart tissue from a chronic chagasic patient was stained for
      both CD8 and CD4 by immunochemistry. Chagasic patients showed higher frequencies
      of DP T cells (2.1% +/- 0.9) compared with healthy (1.1% +/- 0.5) and non
      chagasic cardiomyopathy (1.2% +/- 0.4) donors. DP T cells from Chagasic patients
      also expressed more HLA-DR, CD38 and perforin and had higher frequencies of T.
      cruzi K1-specific cells. IFN-gamma production in K1-specific cells was higher in
      asymptomatic patients after polyclonal stimulation, while these cells tended to
      degranulate more in symptomatic donors. Immunochemistry revealed that double
      positive T cells infiltrate the cardiac tissue of a chagasic donor. CONCLUSIONS:
      Chagasic patients have higher percentages of circulating double positive T cells
      expressing activation markers, potential effector molecules and greater class I
      antigenic specificity against T. cruzi. Although K1 tetramer positive DP T cell
      produced little IFN-gamma, they displayed degranulation activity that was
      increased in symptomatic patients. Moreover, K1-specific DP T cells can migrate
      to the heart tissue.

PMID- 21886855
TI  - The susceptibility of trypanosomatid pathogens to PI3/mTOR kinase inhibitors
      affords a new opportunity for drug repurposing.
AB  - BACKGROUND: Target repurposing utilizes knowledge of "druggable" targets obtained
      in one organism and exploits this information to pursue new potential drug
      targets in other organisms. Here we describe such studies to evaluate whether
      inhibitors targeting the kinase domain of the mammalian Target of Rapamycin
      (mTOR) and human phosphoinositide-3-kinases (PI3Ks) show promise against the
      kinetoplastid parasites Trypanosoma brucei, T. cruzi, Leishmania major, and L.
      donovani. The genomes of trypanosomatids encode at least 12 proteins belonging to
      the PI3K protein superfamily, some of which are unique to parasites. Moreover,
      the shared PI3Ks differ greatly in sequence from those of the human host, thereby
      providing opportunities for selective inhibition. METHODOLOGY/PRINCIPAL FINDINGS:
      We focused on 8 inhibitors targeting mTOR and/or PI3Ks selected from various
      stages of pre-clinical and clinical development, and tested them against in vitro
      parasite cultures and in vivo models of infection. Several inhibitors showed
      micromolar or better efficacy against these organisms in culture. One compound,
      NVP-BEZ235, displayed sub-nanomolar potency, efficacy against cultured parasites,
      and an ability to clear parasitemia in an animal model of T. brucei rhodesiense
      infection. CONCLUSIONS/SIGNIFICANCE: These studies strongly suggest that
      mammalian PI3/TOR kinase inhibitors are a productive starting point for anti
      trypanosomal drug discovery. Our data suggest that NVP-BEZ235, an advanced
      clinical candidate against solid tumors, merits further investigation as an agent
      for treating African sleeping sickness.

PMID- 21886856
TI  - Complete genome sequence of Rhodospirillum rubrum type strain (S1).
AB  - Rhodospirillum rubrum (Esmarch 1887) Molisch 1907 is the type species of the
      genus Rhodospirillum, which is the type genus of the family Rhodospirillaceae in
      the class Alphaproteobacteria. The species is of special interest because it is
      an anoxygenic phototroph that produces extracellular elemental sulfur (instead of
      oxygen) while harvesting light. It contains one of the most simple photosynthetic
      systems currently known, lacking light harvesting complex 2. Strain S1(T) can
      grow on carbon monoxide as sole energy source. With currently over 1,750 PubMed
      entries, R. rubrum is one of the most intensively studied microbial species, in
      particular for physiological and genetic studies. Next to R. centenum strain SW,
      the genome sequence of strain S1(T) is only the second genome of a member of the
      genus Rhodospirillum to be published, but the first type strain genome from the
      genus. The 4,352,825 bp long chromosome and 53,732 bp plasmid with a total of
      3,850 protein-coding and 83 RNA genes were sequenced as part of the DOE Joint
      Genome Institute Program DOEM 2002.

PMID- 21886857
TI  - Complete genome sequence of the thermophilic sulfur-reducer Hippea maritima type
      strain (MH(2)).
AB  - Hippea maritima (Miroshnichenko et al. 1999) is the type species of the genus
      Hippea, which belongs to the family Desulfurellaceae within the class
      Deltaproteobacteria. The anaerobic, moderately thermophilic marine sulfur-reducer
      was first isolated from shallow-water hot vents in Matipur Harbor, Papua New
      Guinea. H. maritima was of interest for genome sequencing because of its isolated
      phylogenetic location, as a distant next neighbor of the genus Desulfurella.
      Strain MH(2) (T) is the first type strain from the order Desulfurellales with a
      completely sequenced genome. The 1,694,430 bp long linear genome with its 1,723
      protein-coding and 57 RNA genes consists of one circular chromosome and is a part
      of the Genomic Encyclopedia of Bacteria and Archaea project.

PMID- 21886858
TI  - Complete genome sequence of the extremely halophilic Halanaerobium praevalens
      type strain (GSL).
AB  - Halanaerobium praevalens Zeikus et al. 1984 is the type species of the genus
      Halanaerobium, which in turn is the type genus of the family Halanaerobiaceae.
      The species is of interest because it is able to reduce a variety of nitro
      substituted aromatic compounds at a high rate, and because of its ability to
      degrade organic pollutants. The strain is also of interest because it functions
      as a hydrolytic bacterium, fermenting complex organic matter and producing
      intermediary metabolites for other trophic groups such as sulfate-reducing and
      methanogenic bacteria. It is further reported as being involved in carbon removal
      in the Great Salt Lake, its source of isolation. This is the first completed
      genome sequence of a representative of the genus Halanaerobium and the second
      genome sequence from a type strain of the family Halanaerobiaceae. The 2,309,262
      bp long genome with its 2,110 protein-coding and 70 RNA genes is a part of the
      Genomic Encyclopedia of Bacteria and Archaea project.

PMID- 21886859
TI  - Complete genome sequence of Nitratifractor salsuginis type strain (E9I37-1).
AB  - Nitratifractor salsuginis Nakagawa et al. 2005 is the type species of the genus
      Nitratifractor, a member of the family Nautiliaceae. The species is of interest
      because of its high capacity for nitrate reduction via conversion to N(2) through
      respiration, which is a key compound in plant nutrition. The strain is also of
      interest because it represents the first mesophilic and facultatively anaerobic
      member of the Epsilonproteobacteria reported to grow on molecular hydrogen. This
      is the first completed genome sequence of a member of the genus Nitratifractor
      and the second sequence from the family Nautiliaceae. The 2,101,285 bp long
      genome with its 2,121 protein-coding and 54 RNA genes is a part of the Genomic
      Encyclopedia of Bacteria and Archaea project.

PMID- 21886860
TI  - Complete genome sequence of Mahella australiensis type strain (50-1 BON).
AB  - Mahella australiensis Bonilla Salinas et al. 2004 is the type species of the
      genus Mahella, which belongs to the family Thermoanaerobacteraceae. The species
      is of interest because it differs from other known anaerobic spore-forming
      bacteria in its G+C content, and in certain phenotypic traits, such as carbon
      source utilization and relationship to temperature. Moreover, it has been
      discussed that this species might be an indigenous member of petroleum and oil
      reservoirs. This is the first completed genome sequence of a member of the genus
      Mahella and the ninth completed type strain genome sequence from the family
      Thermoanaerobacteraceae. The 3,135,972 bp long genome with its 2,974 protein
      coding and 59 RNA genes is a part of the Genomic Encyclopedia of Bacteria and
      Archaea project.

PMID- 21886861
TI  - Complete genome sequence of Tsukamurella paurometabola type strain (no. 33).
AB  - Tsukamurella paurometabola corrig. (Steinhaus 1941) Collins et al. 1988 is the
      type species of the genus Tsukamurella, which is the type genus to the family
      Tsukamurellaceae. The species is not only of interest because of its isolated
      phylogenetic location, but also because it is a human opportunistic pathogen with
      some strains of the species reported to cause lung infection, lethal meningitis,
      and necrotizing tenosynovitis. This is the first completed genome sequence of a
      member of the genus Tsukamurella and the first genome sequence of a member of the
      family Tsukamurellaceae. The 4,479,724 bp long genome contains a 99,806 bp long
      plasmid and a total of 4,335 protein-coding and 56 RNA genes, and is a part of
      the Genomic Encyclopedia of Bacteria and Archaea project.

PMID- 21886862
TI  - Complete genome sequence of Haliscomenobacter hydrossis type strain (O).
AB  - Haliscomenobacter hydrossis van Veen et al. 1973 is the type species of the genus
      Haliscomenobacter, which belongs to order "Sphingobacteriales". The species is of
      interest because of its isolated phylogenetic location in the tree of life,
      especially the so far genomically uncharted part of it, and because the organism
      grows in a thin, hardly visible hyaline sheath. Members of the species were
      isolated from fresh water of lakes and from ditch water. The genome of H.
      hydrossis is the first completed genome sequence reported from a member of the
      family "Saprospiraceae". The 8,771,651 bp long genome with its three plasmids of
      92 kbp, 144 kbp and 164 kbp length contains 6,848 protein-coding and 60 RNA
      genes, and is a part of the Genomic Encyclopedia of Bacteria and Archaea project.

PMID- 21886863
TI  - Complete genome sequence of Treponema succinifaciens type strain (6091).
AB  - Treponema succinifaciens Cwyk and Canale-Parola 1981 is of interest because this
      strictly anaerobic, apathogenic member of the genus Treponema oxidizes
      carbohydrates and couples the Embden-Meyerhof pathway via activity of a pyruvate
      formate lyase to the production of acetyl-coenzyme A and formate. This feature
      separates this species from most other anaerobic spirochetes. The genome of T.
      succinifaciens 6091(T) is only the second completed and published type strain
      genome from the genus Treponema in the family Spirochaetaceae. The 2,897,425 bp
      long genome with one plasmid harbors 2,723 protein-coding and 63 RNA genes and is
      a part of the Genomic Encyclopedia of Bacteria and Archaea project.

PMID- 21886864
TI  - Complete genome sequence of Syntrophobotulus glycolicus type strain (FlGlyR).
AB  - Syntrophobotulus glycolicus Friedrich et al. 1996 is currently the only member of
      the genus Syntrophobotulus within the family Peptococcaceae. The species is of
      interest because of its isolated phylogenetic location in the genome-sequenced
      fraction of tree of life. When grown in pure culture with glyoxylate as carbon
      source the organism utilizes glyoxylate through fermentative oxidation, whereas,
      when grown in syntrophic co-culture with homoacetogenic or methanogenic bacteria,
      it is able to oxidize glycolate to carbon dioxide and hydrogen. No other organic
      or inorganic carbon source is utilized by S. glycolicus. The subdivision of the
      family Peptococcaceae into genera does not reflect the natural relationships,
      particularly regarding the genera most closely related to Syntrophobotulus. Both
      Desulfotomaculum and Pelotomaculum are paraphyletic assemblages, and the
      taxonomic classification is in significant conflict with the 16S rRNA data. S.
      glycolicus is already the ninth member of the family Peptococcaceae with a
      completely sequenced and publicly available genome. The 3,406,739 bp long genome
      with its 3,370 protein-coding and 69 RNA genes is a part of the Genomic
      Encyclopedia of Bacteria and Archaea project.

PMID- 21886865
TI  - Complete genome sequence of the hyperthermophilic chemolithoautotroph Pyrolobus
      fumarii type strain (1A).
AB  - Pyrolobus fumarii Blochl et al. 1997 is the type species of the genus Pyrolobus,
      which belongs to the crenarchaeal family Pyrodictiaceae. The species is a
      facultatively microaerophilic non-motile crenarchaeon. It is of interest because
      of its isolated phylogenetic location in the tree of life and because it is a
      hyperthermophilic chemolithoautotroph known as the primary producer of organic
      matter at deep-sea hydrothermal vents. P. fumarii exhibits currently the highest
      optimal growth temperature of all life forms on earth (106 degrees C). This is
      the first completed genome sequence of a member of the genus Pyrolobus to be
      published and only the second genome sequence from a member of the family
      Pyrodictiaceae. Although Diversa Corporation announced the completion of
      sequencing of the P. fumarii genome on September 25, 2001, this sequence was
      never released to the public. The 1,843,267 bp long genome with its 1,986 protein
      coding and 52 RNA genes is a part of the Genomic Encyclopedia of Bacteria and
      Archaea project.

PMID- 21886866
TI  - Complete genome sequence of the acetate-degrading sulfate reducer Desulfobacca
      acetoxidans type strain (ASRB2).
AB  - Desulfobacca acetoxidans Elferink et al. 1999 is the type species of the genus
      Desulfobacca, which belongs to the family Syntrophaceae in the class
      Deltaproteobacteria. The species was first observed in a study on the competition
      of sulfate-reducers and acetoclastic methanogens for acetate in sludge. D.
      acetoxidans is considered to be the most abundant acetate-degrading sulfate
      reducer in sludge. It is of interest due to its isolated phylogenetic location in
      the 16S rRNA-based tree of life. This is the second completed genome sequence of
      a member of the family Syntrophaceae to be published and only the third genome
      sequence from a member of the order Syntrophobacterales. The 3,282,536 bp long
      genome with its 2,969 protein-coding and 54 RNA genes is a part of the Genomic
      Encyclopedia of Bacteria and Archaea project.

PMID- 21886867
TI  - TheViral MetaGenome Annotation Pipeline(VMGAP):an automated tool for the
      functional annotation of viral Metagenomic shotgun sequencing data.
AB  - In the past few years, the field of metagenomics has been growing at an
      accelerated pace, particularly in response to advancements in new sequencing
      technologies. The large volume of sequence data from novel organisms generated by
      metagenomic projects has triggered the development of specialized databases and
      tools focused on particular groups of organisms or data types. Here we describe a
      pipeline for the functional annotation of viral metagenomic sequence data. The
      Viral MetaGenome Annotation Pipeline (VMGAP) pipeline takes advantage of a number
      of specialized databases, such as collections of mobile genetic elements and
      environmental metagenomes to improve the classification and functional prediction
      of viral gene products. The pipeline assigns a functional term to each predicted
      protein sequence following a suite of comprehensive analyses whose results are
      ranked according to a priority rules hierarchy. Additional annotation is provided
      in the form of enzyme commission (EC) numbers, GO/MeGO terms and Hidden Markov
      Models together with supporting evidence.

PMID- 21886868
TI  - Effects of Floor Level and Building Type on Residential Levels of Outdoor and
      Indoor Polycyclic Aromatic Hydrocarbons, Black Carbon, and Particulate Matter in
      New York City.
AB  - Consideration of the relationship between residential floor level and
      concentration of traffic-related airborne pollutants may predict individual
      residential exposure among inner city dwellers more accurately. Our objective was
      to characterize the vertical gradient of residential levels of polycyclic
      aromatic hydrocarbons (PAH; dichotomized into Sigma(8)PAH(semivolatile) (MW 178
      206), and Sigma(8)PAH(nonvolatile) (MW 228-278), black carbon (BC), PM(2.5)
      (particulate matter) by floor level (FL), season and building type. We
      hypothesize that PAH, BC and PM(2.5) concentrations may decrease with higher FL
      and the vertical gradients of these compounds would be affected by heating season
      and building type. PAH, BC and PM(2.5) were measured over a two-week period
      outdoor and indoor of the residences of a cohort of 5-6 year old children (n =
      339) living in New York City's Northern Manhattan and the Bronx. Airborne
      pollutant levels were analyzed by three categorized FL groups (0-2nd, 3rd-5th,
      and 6th-32nd FL) and two building types (low-rise versus high-rise apartment
      building). Indoor Sigma(8)PAH(nonvolatile) and BC levels declined with increasing
      FL. During the nonheating season, the median outdoor Sigma(8)PAH(nonvolatile,)
      but not Sigma(8)PAH(semivolatile), level at 6th-2nd FL was 1.5-2 times lower than
      levels measured at lower FL. Similarly, outdoor and indoor BC concentrations at
      6th-32nd FL were significantly lower than those at lower FL only during the
      nonheating season (p < 0.05). In addition, living in a low-rise building was
      associated significantly with higher levels of Sigma(8)PAH(nonvolatile) and BC.
      These results suggest that young inner city children may be exposed to varying
      levels of air pollutants depending on their FL, season, and building type.

PMID- 21886870
TI  - Telecare system for cardiac surgery patients: implementation and effectiveness.
AB  - OBJECTIVES: To manage a patient's blood pressure and recovery, and to reduce
      unnecessary hospital visits after heart surgery, we developed and established a
      telecare service. METHODS: We established and test-operated the system that
      enabled biometric data to be measured and monitored at home, and directed
      connections to the video consultation with monitoring personnel and medical staff
      when abnormal symptoms were detected. RESULTS: As a result of using the telecare
      service with patients discharged from the hospital after undergoing heart
      surgery, the patients were mostly satisfied with the service and use of the
      equipment, and some patients wanted to actually receive the service continuously
      along with a device which could be more easily used. CONCLUSIONS: Telecare
      services are greatly needed for patients discharged after heart surgery for a
      certain period of time. A model should be developed which provides devices
      necessary for each disease in package form and customizes the content and
      services in one package.

PMID- 21886871
TI  - Development of an electronic claim system based on an integrated electronic
      health record platform to guarantee interoperability.
AB  - OBJECTIVES: We design and develop an electronic claim system based on an
      integrated electronic health record (EHR) platform. This system is designed to be
      used for ambulatory care by office-based physicians in the United States. This is
      achieved by integrating various medical standard technologies for
      interoperability between heterogeneous information systems. METHODS: The
      developed system serves as a simple clinical data repository, it automatically
      fills out the Centers for Medicare and Medicaid Services (CMS)-1500 form based on
      information regarding the patients and physicians' clinical activities. It
      supports electronic insurance claims by creating reimbursement charges. It also
      contains an HL7 interface engine to exchange clinical messages between
      heterogeneous devices. RESULTS: The system partially prevents physician
      malpractice by suggesting proper treatments according to patient diagnoses and
      supports physicians by easily preparing documents for reimbursement and
      submitting claim documents to insurance organizations electronically, without
      additional effort by the user. To show the usability of the developed system, we
      performed an experiment that compares the time spent filling out the CMS-1500
      form directly and time required create electronic claim data using the developed
      system. From the experimental results, we conclude that the system could save
      considerable time for physicians in making claim documents. CONCLUSIONS: The
      developed system might be particularly useful for those who need a reimbursement
      specialized EHR system, even though the proposed system does not completely
      satisfy all criteria requested by the CMS and Office of the National Coordinator
      for Health Information Technology (ONC). This is because the criteria are not
      sufficient but necessary condition for the implementation of EHR systems. The
      system will be upgraded continuously to implement the criteria and to offer more
      stable and transparent transmission of electronic claim data.

PMID- 21886869
TI  - The Role of Proteomics in the Diagnosis and Treatment of Women's Cancers: Current
      Trends in Technology and Future Opportunities.
AB  - Technological and scientific innovations over the last decade have greatly
      contributed to improved diagnostics, predictive models, and prognosis among
      cancers affecting women. In fact, an explosion of information in these areas has
      almost assured future generations that outcomes in cancer will continue to
      improve. Herein we discuss the current status of breast, cervical, and ovarian
      cancers as it relates to screening, disease diagnosis, and treatment options.
      Among the differences in these cancers, it is striking that breast cancer has
      multiple predictive tests based upon tumor biomarkers and sophisticated,
      individualized options for prescription therapeutics while ovarian cancer lacks
      these tools. In addition, cervical cancer leads the way in innovative, cancer
      preventative vaccines and multiple screening options to prevent disease
      progression. For each of these malignancies, emerging proteomic technologies
      based upon mass spectrometry, stable isotope labeling with amino acids, high
      throughput ELISA, tissue or protein microarray techniques, and click chemistry in
      the pursuit of activity-based profiling can pioneer the next generation of
      discovery. We will discuss six of the latest techniques to understand proteomics
      in cancer and highlight research utilizing these techniques with the goal of
      improvement in the management of women's cancers.

PMID- 21886872
TI  - An Automated Measurement of Ciliary Beating Frequency using a Combined Optical
      Flow and Peak Detection.
AB  - OBJECTIVES: The mucociliary transport system is a major defense mechanism of the
      respiratory tract. The performance of mucous transportation in the nasal cavity
      can be represented by a ciliary beating frequency (CBF). This study proposes a
      novel method to measure CBF by using optical flow. METHODS: To obtain objective
      estimates of CBF from video images, an automated computer-based image processing
      technique is developed. This study proposes a new method based on optical flow
      for image processing and peak detection for signal processing. We compare the
      measuring accuracy of the method in various combinations of image processing
      (optical flow versus difference image) and signal processing (fast Fourier
      transform [FFT] vs. peak detection [PD]). The digital high-speed video method
      with a manual count of CBF in slow motion video play, is the gold-standard in CBF
      measurement. We obtained a total of fifty recorded ciliated sinonasal epithelium
      images to measure CBF from the Department of Otolaryngology. The ciliated
      sinonasal epithelium images were recorded at 50-100 frames per second using a
      charge coupled device camera with an inverted microscope at a magnification of
      *1,000. RESULTS: The mean square errors and variance for each method were 1.24,
      0.84 Hz; 11.8, 2.63 Hz; 3.22, 1.46 Hz; and 3.82, 1.53 Hz for optical flow (OF) +
      PD, OF + FFT, difference image [DI] + PD, and DI + FFT, respectively. Of the four
      methods, PD using optical flow showed the best performance for measuring the CBF
      of nasal mucosa. CONCLUSIONS: The proposed method was able to measure CBF more
      objectively and efficiently than what is currently possible.

PMID- 21886873
TI  - Evaluation of Term Ranking Algorithms for Pseudo-Relevance Feedback in MEDLINE
      Retrieval.
AB  - OBJECTIVES: The purpose of this study was to investigate the effects of query
      expansion algorithms for MEDLINE retrieval within a pseudo-relevance feedback
      framework. METHODS: A number of query expansion algorithms were tested using
      various term ranking formulas, focusing on query expansion based on pseudo
      relevance feedback. The OHSUMED test collection, which is a subset of the MEDLINE
      database, was used as a test corpus. Various ranking algorithms were tested in
      combination with different term re-weighting algorithms. RESULTS: Our
      comprehensive evaluation showed that the local context analysis ranking
      algorithm, when used in combination with one of the reweighting algorithms -
      Rocchio, the probabilistic model, and our variants - significantly outperformed
      other algorithm combinations by up to 12% (paired t-test; p < 0.05). In a pseudo
      relevance feedback framework, effective query expansion would be achieved by the
      careful consideration of term ranking and re-weighting algorithm pairs, at least
      in the context of the OHSUMED corpus. CONCLUSIONS: Comparative experiments on
      term ranking algorithms were performed in the context of a subset of MEDLINE
      documents. With medical documents, local context analysis, which uses co
      occurrence with all query terms, significantly outperformed various term ranking
      methods based on both frequency and distribution analyses. Furthermore, the
      results of the experiments demonstrated that the term rank-based re-weighting
      method contributed to a remarkable improvement in mean average precision.

PMID- 21886874
TI  - The uses of the smartphone for doctors: an empirical study from samsung medical
      center.
AB  - OBJECTIVES: In healthcare, mobile computing made possible by smartphones is
      becoming an important tool among healthcare professionals. However, currently
      there is very little research into the effectiveness of such applications of
      technology. This study aims to present a framework for a smartphone application
      to give doctors mobile access to patient information, then review the
      consequences of its use and discuss its future direction. METHODS: Since 2003
      when Samsung Medical Center introduced its first mobile application, a need to
      develop a new application targeting the latest smartphone technology was
      identified. To that end, an application named Dr. SMART S was officially launched
      on December 22nd, 2010. RESULTS: We analyzed the usage data of the application
      for a month until April 25th, 2011. On average, 170 doctors (13% of the entire
      body of doctors) logged on 2.4 times per day and that number keeps growing. The
      number was uniformly distributed across all working hours, with exceptions of
      heavy accesses around 6-8 AM and 4-6 PM when doctors do their regular rounds to
      see the patients. The most commonly accessed content was inpatient information,
      this constituted 78.6% of all accesses, within this 50% was to accesses lab
      results. CONCLUSIONS: Looking at the usage data, we can see the use of Dr. SMART
      S by doctors is growing in sync with the popularity of smartphones. Since u
      Health seem an inevitable future trend, a more rigorous study needs to be
      conducted on how such mobile applications as Dr. SMART S affect the quality of
      care and patient safety to derive directions for further improvements.

PMID- 21886875
TI  - Transfer of flexor carpi ulnaris branches to selectively restore AIN function in
      median nerve sections: Anatomical feasibility study and case report.
AB  - BACKGROUND: In recent years, distal nerve transfers have become a valid tool for
      nerve reconstruction. Though grafts remain the gold standard for proximal median
      nerve injuries, a new distal transfer of flexor carpi ulnaris branches of the
      ulnar nerve to selectively restore anterior interosseous nerve function,
      concomitant with median nerve graft repair, could enhance outcomes. The objective
      of this paper is to anatomically analyze a technique to selectively reinnervate
      the thumb and index flexors. METHODS: Both the median and ulnar nerves were
      dissected in 10 cadavers. First and second branches to the flexor carpi ulnaris
      (FCU) were measured for length at its emergence from the ulnar nerve, and for
      width. The emergence of the AIN, just proximal to the arch of the flexor
      digitorum superficialis, was dissected, and the distance measured from this point
      to its motor entry at the long flexor pollicis and its branch to the long index
      flexor. A tensionless repair was performed between one FCU branch and the AIN.
      RESULTS: The mean AIN length was 32.3+/-8.20 mm and width 2.4+/-0.49 mm. The
      first branch from the ulnar nerve to the FCU measured 20.8+/-2.04 mm and 1.52+/
      0.44 mm, while the second, more distal branch measured 24.3+/-6.71 and 1.9+/-0.17
      mm, respectively. In all dissections, it was possible to contact both the
      proximal and distal branches of the ulnar nerve to the FCU with the distal stump
      of the divided AIN, with no tension or need for interposed nerve grafts.
      CONCLUSIONS: Though proximal reconstruction remains the gold standard, new distal
      nerve transfer techniques may improve outcomes.

PMID- 21886877
TI  - QR codes in neurosurgery.

PMID- 21886876
TI  - Anomalous vertebral artery compression of the spinal cord at the cervicomedullary
      junction.
AB  - BACKGROUND: Myelopathy from ectatic vertebral artery compression of the spinal
      cord at the cervicomedullary junction is a rare condition. CASE DESCRIPTION: A 63
      year-old female was originally diagnosed with occult hydrocephalus syndrome after
      presenting with symptoms of ataxia and urinary incontinence. Ventriculoperitoneal
      shunting induced an acute worsening of the patient's symptoms as she immediately
      developed a sensory myelopathy. An MR scan demonstrated multiple congenital
      abnormalities including cervicomedullary stenosis with anomalous vertebral artery
      compression of the dorsal spinal cord at the cervicomedullary junction. The
      patient was taken to surgery for a suboccipital craniectomy, C1-2 laminectomy,
      vertebral artery decompression, duraplasty, and shunt ligation. Intraoperative
      findings confirmed preoperative radiography with ectactic vertebral arteries
      deforming the dorsal aspect of the spinal cord. There were no procedural
      complications and at a 6-month follow-up appointment, the patient had experienced
      a marked improvement in her preoperative signs and symptoms. CONCLUSION:
      Myelopathy from ectatic vertebral artery compression at the cervicomedullary
      junction is a rare disorder amenable to operative neurovascular decompression.

PMID- 21886878
TI  - Predictors of inpatient complications and outcomes following surgical resection
      of hypothalamic hamartomas.
AB  - BACKGROUND: Our aim was to identify the preoperative factors associated with a
      greater risk of poor inpatient outcomes in those undergoing resection of
      hypothalamic hamartomas. METHODS: We performed a multi-institutional
      retrospective cohort analysis via the Nationwide Inpatient Sample (1998 - 2007).
      Patients of any age who underwent resection of hypothalamic hamartomas were
      identified by ICD-9 coding. The primary outcomes included inpatient
      complications, length of stay (LOS), and total charges. Multivariate regression
      models were constructed to analyze the outcomes. RESULTS: Two hundred and eighty
      two patients were identified with a mean age of 27.7 years, with most being male
      (53.2%), Caucasian (78.9%), privately insured (69.3%), and treated electively
      (74.7%) at academic centers (91.7%). A majority (82.2%) had Elixhauser
      comorbidity scores of < 1, indicating few comorbidities. No inpatient deaths were
      reported. Mean LOS was 7.39 days and the mean total hospital charges were
      $53,935. Overall, 19.5% developed an inpatient complication, primarily stroke
      (16.7%). Female gender, ethnic / racial minorities, higher comorbidity scores,
      private insurance, and non-academic hospitals were associated with greater LOS
      and total charges. Private insurance (Odds Ratio, OR: 1.59, P = 0.045) and
      academic hospitals (OR: 1.43, P = 0.008) were associated with significantly
      higher odds of any complication. Minority race / ethnicity was associated with a
      minimal increase in the odds of postoperative stroke (OR: 1.02, P < 0.001)
      relative to Caucasians. CONCLUSIONS: Through an analysis of a 10-year multi
      institutional database, we have described the surgical outcomes of patients
      undergoing resection of hypothalamic hamartomas. Results demonstrate significant
      inpatient morbidity, particularly postoperative stroke. Patient- and institution
      level factors should be considered in determining the perioperative risk for such
      patients.

PMID- 21886879
TI  - MRS findings in electrical status epilepticus in sleep: Report of two cases.
AB  - BACKGROUND: To evaluate the changes in brain metabolites by H1 magnetic resonance
      spectroscopy in two patients with electrical status epilepticus. CASE
      DESCRIPTION: Two boys (aged 6 and 7 years) with electrical status epilepticus in
      sleep have been evaluated. N-acetyl aspartate levels were slightly elevated, and
      showed no decline in the postictal period. Creatine and choline levels were
      similar to that in controls. No evidence of neuronal cell damage was seen.
      CONCLUSION: Electrical status epilepticus is a balanced condition of
      hypermetabolism, when not accompanied with seizure.

PMID- 21886881
TI  - Response to "Unnecessary spinal surgery".

PMID- 21886882
TI  - Safety and efficacy of rhBMP2 in posterior cervical spinal fusion for subaxial
      degenerative spine disease: Analysis of outcomes in 204 patients.
AB  - BACKGROUND: Many studies offer excellent demonstration of the ability of bone
      morphogenic protein (BMP) to enhance fusion rates in anterior as well as
      posterior lumbar surgery. Recently, BMP has also been shown to increase
      arthrodesis rates in anterior cervical surgery, albeit with concomitant increases
      in complication rates. To date, however, few studies have investigated the safety
      and efficacy of BMP in cervical surgeries approached posteriorly. METHODS: We
      retrospectively reviewed 204 consecutive patients with degenerative cervical
      spinal conditions necessitating posterior cervical fusion at a single institution
      over the past 4 years. The incidence of postoperative mechanical neck pain,
      fusion rates, as well as neurologic outcomes were compared between patients who
      received BMP vs those who did not receive BMP intraoperatively. RESULTS: There
      were no significant differences in preoperative variables between the non-BMP vs
      the BMP cohorts. Over an average follow-up of 24.2 months, there were no
      significant differences between the two cohorts in duration of hospitalization,
      cerebrospinal fluid leakage, deep vein thrombosis, pulmonary embolism,
      hyperostosis, infection, pneumonia, hematoma, C5 palsy, wound dehiscence,
      reoperation rates, or Nurick/ASIA scores. Eleven (7.1%) patients in the non-BMP
      group experienced instrumentation failure vs none in the BMP group (P=0.06).
      Patients receiving BMP had a significantly increased rate of fusion by the chi
      square test (P=0.01) and the log-rank test (P=0.02). However, patients receiving
      BMP also had the highest rates of recurrent/persistent neck pain by the chi
      square test (P=0.003) and the log-rank test (P=0.01). CONCLUSIONS: To date, few
      studies have evaluated the safety and efficacy of BMP in the posterior cervical
      spine. Here, we show that BMP usage does not increase complication rates, but it
      significantly increases arthrodesis rates and also may increase the rate of
      recurrent/persistent neck pain.

PMID- 21886883
TI  - Trends over time in the management of 2253 patients with cerebral aneurysms: A
      single practice experience.
AB  - BACKGROUND: To better understand the longitudinal trend in the proportion of
      techniques employed for cerebral aneurysm treatment, we reviewed our experience
      with 2253 patients over the last 11 years. METHODS: We reviewed data in our
      prospective aneurysm database for all consecutive patients treated from January
      1998 through December 2009. Data regarding age, sex, aneurysm location, presence
      or absence of hemorrhage, Fisher grade, clinical grade, treatment methods, length
      of hospitalization, and mortality rates by the time of discharge were retrieved
      and retrospectively analyzed. The most common aneurysm types were subsequently
      classified and analyzed separately. RESULTS: The patient population included 663
      males (29%) and 1590 females (71%). A total of 2253 patients presented with 3413
      aneurysms; 1523 (63%) of the aneurysms were diagnosed as aneurysmal subarachnoid
      hemorrhage. A total of 2411 (71%) aneurysms were treated. Overall, 645 (27%) of
      the 2411 aneurysms underwent endosaccular coiling and 1766 (73%) underwent clip
      ligation; 69 (3%) of these aneurysms required both treatment modalities. The
      percentage of all aneurysms treated by endosaccular coiling increased from 8%
      (21) in 1998 to 28% (87) in 2009. There was no statistical difference between the
      average length of hospitalization for patients who underwent endosaccular coiling
      and clip ligation for their ruptured (P = 0.19) and unruptured (P = 0.80)
      aneurysms during this time period. CONCLUSIONS: In our practice, endovascular
      treatment has continued to be more frequently employed to treat cerebral
      aneurysms. This technique has had the greatest proportional increase in the
      treatment of posterior circulation aneurysms.

PMID- 21886884
TI  - Sensitivity and specificity in transcranial motor-evoked potential monitoring
      during neurosurgical operations.
AB  - BACKGROUND: Intraoperative transcranial motor-evoked potential (TCMEP) monitoring
      is widely performed during neurosurgical operations. Sensitivity and specificity
      in TCMEP during neurosurgical operations were examined according to the type of
      operation. METHODS: TCMEP monitoring was performed during 283 neurosurgical
      operations for patients without preoperative motor palsy, including 121 spinal
      operations, 84 cerebral aneurysmal operations, and 31 brain tumor operations.
      Transcranial stimulation at 100-600 V was applied by screw electrodes placed in
      the scalp and electromyographic responses were recorded with surface electrodes
      placed on the affected muscles. To exclude the effects of muscle relaxants on
      TCMEP, compound muscle action potential (CMAP) by supramaximal stimulation of the
      peripheral nerve immediately after transcranial stimulation was used for
      compensation of TCMEP. RESULTS: In spinal operations, with an 80% reduction in
      amplitude as the threshold for motor palsy, the sensitivity and specificity with
      CMAP compensation were 100% and 96.4%, respectively. In aneurysmal operations,
      with a 70% reduction in amplitude as the threshold for motor palsy, the
      sensitivity and specificity with CMAP compensation were 100% and 94.8%,
      respectively. Compensation by CMAP was especially useful in aneurysmal
      operations. In all neurosurgical operations, with a 70% reduction in amplitude as
      the threshold for motor palsy, the sensitivity and specificity with CMAP
      compensation were 95.0% and 90.9%, respectively. CONCLUSIONS: Intraoperative
      TCMEP monitoring is a significantly reliable method for preventing postoperative
      motor palsy in both cranial and spinal surgery. A 70% reduction in the
      compensated amplitude is considered to be a suitable alarm point in all
      neurological operations.

PMID- 21886880
TI  - Immunoexcitotoxicity as a central mechanism in chronic traumatic encephalopathy-A
      unifying hypothesis.
AB  - Some individuals suffering from mild traumatic brain injuries, especially
      repetitive mild concussions, are thought to develop a slowly progressive
      encephalopathy characterized by a number of the neuropathological elements shared
      with various neurodegenerative diseases. A central pathological mechanism
      explaining the development of progressive neurodegeneration in this subset of
      individuals has not been elucidated. Yet, a large number of studies indicate that
      a process called immunoexcitotoxicity may be playing a central role in many
      neurodegenerative diseases including chronic traumatic encephalopathy (CTE). The
      term immunoexcitotoxicity was first coined by the lead author to explain the
      evolving pathological and neurodevelopmental changes in autism and the Gulf War
      Syndrome, but it can be applied to a number of neurodegenerative disorders. The
      interaction between immune receptors within the central nervous system (CNS) and
      excitatory glutamate receptors trigger a series of events, such as extensive
      reactive oxygen species/reactive nitrogen species generation, accumulation of
      lipid peroxidation products, and prostaglandin activation, which then leads to
      dendritic retraction, synaptic injury, damage to microtubules, and mitochondrial
      suppression. In this paper, we discuss the mechanism of immunoexcitotoxicity and
      its link to each of the pathophysiological and neurochemical events previously
      described with CTE, with special emphasis on the observed accumulation of
      hyperphosphorylated tau.

PMID- 21886885
TI  - Spinal cord injury: From inflammation to glial scar.
AB  - BACKGROUND: Glial scar (GS) is the most important inhibitor factor to
      neuroregeneration after spinal cord injury (SCI) and behaves as a tertiary
      lesion. The present review of the literature searched for representative studies
      concerning GS and therapeutic strategies to neuroregeneration. METHODS: The
      author used the PubMed database and Google scholar to search articles published
      in the last 20 years. Key words used were SCI, spinal cord (SC) inflammation, GS,
      and SCI treatment. RESULTS: Both inflammation and GS are considered important
      events after SCI. Despite the fact that firstly they seem to cause benefit, in
      the end they cause more harm than good to neuroregeneration. Each stage has its
      own aspects under the influence of the immune system causing inflammation, from
      the primary to secondary lesion and from those to GS (tertiary lesion).
      CONCLUSION: Future studies should stress the key points where and when GS
      presents itself as an inhibitory factor to neuroregeneration. Considering GS as
      an important event after SCI, the author defends GS as being a tertiary lesion.
      Current strategies are presented with emphasis on stem cells and drug therapy. A
      better understanding will permit the development of a therapeutic basis in the
      treatment of the SCI patients considering each stage of the lesion, with emphasis
      on GS and neuroregeneration.

PMID- 21886886
TI  - Intraventricular trigonal meningioma: Neuronavigation? No, thanks!
AB  - BACKGROUND: Most of the time meningiomas are benign brain tumors and surgical
      removal ensures cure in the vast majority of the cases. Thus, whenever possible,
      complete surgical resection should be the goal of the treatment. METHODS: This is
      a report of our surgical technique for the operative resection of a trigonal
      meningioma in a resource-limited setting. The necessity of accurate and deep
      knowledge of the regional anatomy is outlined. RESULTS: A 44-year-old male
      presented to our outpatient clinic complaining of cephalalgia increasing in
      frequency and intensity over the last month. His neurological exam was normal,
      yet a brain computed tomography scan revealed a lesion in the right trigone of
      the ventricular system. The diagnosis of possible meningioma was set. After
      thoroughly informing the patient, tumor resection was decided. An intraparietal
      sulcus approach was favored without the use of any modern technological aids such
      as intraoperative magnetic resonance imaging or neuronavigation. The
      postoperative course was uneventful and a postoperative computed tomography scan
      demonstrated the complete resection of the tumor. The patient was discharged two
      days later with no neurological deficits. In a two-year-follow-up he remains
      recurrence-free. CONCLUSION: In the current cost-effective era it is still
      possible to safely remove an intraventricular trigonal meningioma without the
      convenience of neuronavigation. Since the best neuronavigator is the profound
      neuroanatomical knowledge, no technological advancement could replace a well
      educated and trained neurosurgeon.

PMID- 21886888
TI  - Costs and frequency of "off-label" use of INFUSE for spinal fusions at one
      institution in 2010.
AB  - BACKGROUND: INFUSE, bone morphogenetic protein-2 combined with bovine Type I
      collagen in the lumbar tapered fusion device (LT Cage), is used to promote
      anterior lumbar interbody fusion (ALIF). In spinal surgery, INFUSE is only
      Federal Drug Administration (FDA) approved for this "on-label" use. While the
      efficacy and possible complications due to INFUSE have been debated, we know less
      about the costs and frequency of "on-label" versus "off-label" use of INFUSE to
      perform spinal fusions. METHODS: At one institution, we determined the costs
      (with overhead) and frequency of utilizing INFUSE "on-label" and "off-label" in
      performing spinal fusions during 2010. RESULTS: During 2010, 177 spinal fusions
      utilized INFUSE. Ninety-six percent, or 170 of 177 spinal fusions, utilized
      INFUSE in an "off-label" capacity at a cost of $4,547,822. Only 4%, or seven of
      177 cases, utilized INFUSE in an "on-label" capacity (ALIF); the total cost was
      $296,419. CONCLUSIONS: In 2010, at one institution, 96% of the spinal fusions
      utilized INFUSE in an off-label capacity (cost $4,547,822), while only 4% were
      performed on-label (cost $296,4194).

PMID- 21886887
TI  - Trigeminal neuralgia as the initial manifestation of temporal glioma: Report of
      three cases and a review of the literature.
AB  - BACKGROUND: It is almost an accepted scenario that trigeminal neuralgia (TN)
      occurs when there is a kind of vascular compression on the root entry zone of
      trigeminal nerve at pons. There are occasional reports about trigeminal neuralgia
      as the presenting sign of intracranial tumors but temporal glioma has rarely been
      included in the list. CASE DESCRIPTION: We report three cases of temporal lobe
      glioma which presented with trigeminal neuralgia as the initial manifestation and
      review the relevant literature briefly. The patients were 19-, 20-, and 31-year
      old males who presented with partially controlled TN. The tumor mass could be
      detected in paraclinical evaluations when the usual modalities of therapy for
      facial pain in our community were not effective. Excisional surgery led in full
      pain control in all the cases. Two of the patients died because of tumor
      recurrence after a year and the other one is being treated by adjuvants.
      CONCLUSION: We add these types of intracranial tumors to the list of the
      etiologies for TN and the possible mechanisms for the initiation of pain in these
      types of intracranial tumors are discussed.

PMID- 21886889
TI  - Spindle cell oncocytoma of the pituitary and pituicytoma: Two tumors mimicking
      pituitary adenoma.
AB  - BACKGROUND: Spindle cell oncocytoma (SCO) and pituicytoma are rare nonfunctioning
      tumors of the pituitary. Both tumors are low grade and macroscopically
      indistinguishable from a nonfunctioning pituitary adenoma.We report one case of
      SCO and one case of pituicytoma and review the previous literature. CASE
      DESCRIPTION: One patient was a 39-year-old man who presented with progressive
      headache, visual blurring, and polyuria of 3-year duration. He underwent partial
      resection (30% of the tumor) and postoperative adjuvant radiation therapy.
      Histopathology revealed SCO. However, after 9 months, the residual tumor grew and
      partial resection (70% of the tumor) was performed again. Four months after the
      second surgery, the tumor recurred again and he underwent transsphenoidal
      resection of the tumor with stable residual tumor to date. The other patient was
      a 59-year-old man who presented with a 3-month history of visual decline,
      fatigue, difficulty in writing, and polyuria. He underwent transsphenoidal
      resection (total) of the tumor. Histopathology revealed pituicytoma. He has been
      stable without evidence of recurrence for 1 year and 4 months. CONCLUSION: To
      date, there are 15 reported cases of SCO and 45 reported cases of pituicytoma
      including our cases. An incomplete resection of the tumor was a significant risk
      factor for recurrence in both SCO and pituicytoma (P = 0.0014 and P = 0.019,
      respectively). These tumors have a tendency to be hypervascular, which may hamper
      total resection. Epithelial membrane antigen (EMA) and mitochondria positivity is
      characteristic to SCO and they are considered to be important immunomarkers to
      distinguish these tumors.

PMID- 21886890
TI  - A review of radio frequency identification technology for the anatomic pathology
      or biorepository laboratory: Much promise, some progress, and more work needed.
AB  - Patient safety initiatives throughout the anatomic laboratory and in
      biorepository laboratories have mandated increasing emphasis on the need for
      accurately identifying and tracking biospecimen assets throughout their
      production lifecycle and for archiving/retrieval purposes. However, increasing
      production volume along with complex workflow characteristics, reliance on manual
      production processes, and required asset movement to disparate destinations
      throughout asset lifecycles continue to challenge laboratory efforts. Radio
      Frequency Identification (RFID) technology, use of radio waves to communicate
      data between electronic tags attached to objects and a reader, shows significant
      potential to facilitate and overcome these hurdles. Advantages over traditional
      barcode labeling include readability without direct line-of-sight alignment to
      the reader, ability to read multiple tags simultaneously, higher data storage
      capacity, faster data transmission rate, and capacity to perform multiple read
      writes of data to the tag. Most importantly, use of radio waves decreases the
      need to manually scan each asset, and at each step, identification or tracking
      event is needed. Temperature monitoring by on-board sensors and three-dimensional
      position tracking are additional potential benefits of using RFID technology. To
      date, barriers to implementation of RFID systems in the anatomic laboratory
      include increased associated costs of tags and readers, system software, data
      security concerns, lack of specific data standards for stored information, and
      potential for technological obsolescence during decades of specimen storage.
      Novel RFID production techniques and increased production capacity are projected
      to lower costs of some tags to a few cents each. Potentially, information
      security concerns can be addressed by techniques such as shielding, data
      encryption, and tag pseudonyms. Commitment by stakeholder groups to develop RFID
      tag data standards for anatomic pathology and biorepository laboratories could
      avoid or mitigate the "islands of data" dilemma presented by barcode usage where
      there are innumerable standards and a consequent paucity of hardware or software
      "plug and play" interoperability. Work remains to be done to establish the
      durability and appropriate shielding of individual tag types for use in harsh
      laboratory environmental conditions, and for long-term archival storage. Finally,
      given the requirements for long-term storage of biospecimen assets, consideration
      should be given to ways of mitigating data isolation due to eventual
      technological obsolescence of a particular RFID technology or software.

PMID- 21886891
TI  - Computerized provider order entry in the clinical laboratory.
AB  - Clinicians have traditionally ordered laboratory tests using paper-based orders
      and requisitions. However, paper orders are becoming increasingly incompatible
      with the complexities, challenges, and resource constraints of our modern
      healthcare systems and are being replaced by electronic order entry systems.
      Electronic systems that allow direct provider input of diagnostic testing or
      medication orders into a computer system are known as Computerized Provider Order
      Entry (CPOE) systems. Adoption of laboratory CPOE systems may offer institutions
      many benefits, including reduced test turnaround time, improved test utilization,
      and better adherence to practice guidelines. In this review, we outline the
      functionality of various CPOE implementations, review the reported benefits, and
      discuss strategies for using CPOE to improve the test ordering process. Further,
      we discuss barriers to the implementation of CPOE systems that have prevented
      their more widespread adoption.

PMID- 21886892
TI  - Review of the current state of whole slide imaging in pathology.
AB  - Whole slide imaging (WSI), or "virtual" microscopy, involves the scanning
      (digitization) of glass slides to produce "digital slides". WSI has been
      advocated for diagnostic, educational and research purposes. When used for remote
      frozen section diagnosis, WSI requires a thorough implementation period coupled
      with trained support personnel. Adoption of WSI for rendering pathologic
      diagnoses on a routine basis has been shown to be successful in only a few
      "niche" applications. Wider adoption will most likely require full integration
      with the laboratory information system, continuous automated scanning, high
      bandwidth connectivity, massive storage capacity, and more intuitive user
      interfaces. Nevertheless, WSI has been reported to enhance specific pathology
      practices, such as scanning slides received in consultation or of legal cases, of
      slides to be used for patient care conferences, for quality assurance purposes,
      to retain records of slides to be sent out or destroyed by ancillary testing, and
      for performing digital image analysis. In addition to technical issues,
      regulatory and validation requirements related to WSI have yet to be adequately
      addressed. Although limited validation studies have been published using WSI
      there are currently no standard guidelines for validating WSI for diagnostic use
      in the clinical laboratory. This review addresses the current status of WSI in
      pathology related to regulation and validation, the provision of remote and
      routine pathologic diagnoses, educational uses, implementation issues, and the
      cost-benefit analysis of adopting WSI in routine clinical practice.

PMID- 21886893
TI  - Automated vector selection of SIVQ and parallel computing integration MATLABTM:
      Innovations supporting large-scale and high-throughput image analysis studies.
AB  - INTRODUCTION: Spatially invariant vector quantization (SIVQ) is a texture and
      color-based image matching algorithm that queries the image space through the use
      of ring vectors. In prior studies, the selection of one or more optimal vectors
      for a particular feature of interest required a manual process, with the user
      initially stochastically selecting candidate vectors and subsequently testing
      them upon other regions of the image to verify the vector's sensitivity and
      specificity properties (typically by reviewing a resultant heat map). In carrying
      out the prior efforts, the SIVQ algorithm was noted to exhibit highly scalable
      computational properties, where each region of analysis can take place
      independently of others, making a compelling case for the exploration of its
      deployment on high-throughput computing platforms, with the hypothesis that such
      an exercise will result in performance gains that scale linearly with increasing
      processor count. METHODS: An automated process was developed for the selection of
      optimal ring vectors to serve as the predicate matching operator in defining
      histopathological features of interest. Briefly, candidate vectors were generated
      from every possible coordinate origin within a user-defined vector selection area
      (VSA) and subsequently compared against user-identified positive and negative
      "ground truth" regions on the same image. Each vector from the VSA was assessed
      for its goodness-of-fit to both the positive and negative areas via the use of
      the receiver operating characteristic (ROC) transfer function, with each
      assessment resulting in an associated area-under-the-curve (AUC) figure of merit.
      RESULTS: Use of the above-mentioned automated vector selection process was
      demonstrated in two cases of use: First, to identify malignant colonic
      epithelium, and second, to identify soft tissue sarcoma. For both examples, a
      very satisfactory optimized vector was identified, as defined by the AUC metric.
      Finally, as an additional effort directed towards attaining high-throughput
      capability for the SIVQ algorithm, we demonstrated the successful incorporation
      of it with the MATrix LABoratory (MATLABTM) application interface. CONCLUSION:
      The SIVQ algorithm is suitable for automated vector selection settings and high
      throughput computation.

PMID- 21886895
TI  - Design, Synthesis and Biological Evaluation of Novel Pyrimido[4,5-d]pyrimidine
      CDK2 Inhibitors as Anti-Tumor Agents.
AB  - A series of 2,5,7-trisubstituted pyrimido[4,5-d]pyrimidine cyclin-dependent
      kinase (CDK2) inhibitors is designed and synthesized. 6-Amino-2-thiouracil is
      reacted with an aldehyde and thiourea to prepare the pyrimido[4,5-d]-pyrimidines.
      Alkylation and amination of the latter ones give different amino derivatives.
      These compounds show potent and selective CDK inhibitory activities and inhibit
      in vitro cellular proliferation in cultured human tumor cells.

PMID- 21886894
TI  - Neglected disease - african sleeping sickness: recent synthetic and modeling
      advances.
AB  - Human African Trypanosomiasis (HAT) also called sleeping sickness is caused by
      subspecies of the parasitic hemoflagellate Trypanosoma brucei that mostly occurs
      in sub-Saharan Africa. The current chemotherapy of the human trypanosomiases
      relies on only six drugs, five of which have been developed more than 30 years
      ago, have undesirable toxic side effects and most of them show drug-resistance.
      Though development of new anti-trypanosomal drugs seems to be a priority area
      research in this area has lagged far behind. The given review mainly focus upon
      the recent synthetic and computer based approaches made by various research
      groups for the development of newer anti-trypanosomal analogues which may have
      improved efficacy and oral bioavailability than the present ones. The given paper
      also attempts to investigate the relationship between the various physiochemical
      parameters and anti-trypanosomal activity that may be helpful in development of
      potent anti-trypanosomal agents against sleeping sickness.

PMID- 21886896
TI  - Design, synthesis and biological evaluation of new 5,5-diarylhydantoin
      derivatives as selective cyclooxygenase-2 inhibitors.
AB  - A new group of 5,5-diarylhydantoin derivatives bearing a methylsulfonyl COX-2
      pharmacophore at the para position of the C-5 phenyl ring were designed and
      synthesized as selective COX-2 inhibitors. In vitro COX-1/COX-2 inhibition
      structure-activity relationships identified 5-[4-(methylsulfonyl)phenyl]-5-phenyl
      hydantoin (4) as a highly potent and selective COX-2 inhibitor (COX-2 IC(50) =
      0.077 MUM; selectivity index > 1298). It was more selective than the reference
      drug celecoxib (COX-2 IC(50) = 0.060 MUM; selectivity index = 405). A molecular
      modeling study where 4 was docked in the binding site of COX-2 indicated that the
      p-MeSO(2) COX-2 pharmacophore group on the C-5 phenyl ring is oriented in the
      vicinity of the COX-2 secondary pocket. The results of this study showed that the
      type of substituent on the N-3 hydantoin ring substituent is important for COX-2
      inhibitory activity.

PMID- 21886897
TI  - Molecular modeling on structure-function analysis of human progesterone receptor
      modulators.
AB  - Considering the significance of progesterone receptor (PR) modulators, the
      present study is explored to envisage the biophoric signals for binding to
      selective PR subtype-A using ligand-based quantitative structure activity
      relationship (QSAR) and pharmacophore space modeling studies on nonsteroidal
      substituted quinoline and cyclocymopol monomethyl ether derivatives. Consensus
      QSAR models (Training set (Tr): n(Tr)=100, R(2) (pred)=0.702; test set (Ts):
      n(Ts)=30, R(2) (pred)=0.705, R(2) (m)=0.635; validation set (Vs): n(Vs)=40, R(2)
      (pred)=0.715, R(2) (m)=0.680) suggest that molecular topology, atomic
      polarizability and electronegativity, atomic mass and van der Waals volume of the
      ligands have influence on the presence of functional atoms (F, Cl, N and O) and
      consequently contribute significant relations on ligand binding affinity.
      Receptor independent space modeling study (Tr: n(Tr)=26, Q(2)=0.927; Ts:
      n(Ts)=60, R(2) (pred)=0.613, R(2) (m)=0.545; Vs: n(Vs)=84, R(2) (pred)=0.611,
      R(2) (m)=0.507) indicates the importance of aromatic ring, hydrogen bond donor,
      molecular hydrophobicity and steric influence for receptor binding. The structure
      function characterization is adjudged with the receptor-based docking study,
      explaining the significance of the mapped molecular attributes for ligand
      receptor interaction in the catalytic cleft of PR-A.

PMID- 21886898
TI  - Preformulation studies of Zidovudine derivatives: Acid dissociation constants,
      differential scanning calorimetry, thermogravimetry, x-ray powder diffractometry
      and aqueous stability studies.
AB  - As part as of the preformulation studies of new 5'-OH derivatives of zidovudine,
      compounds 2-6, their acid dissociation constants, Differential Scanning
      Calorimetry (DSC) and Thermogravimetry (TG) curves, X-Ray Powder diffractograms
      and aqueous stability are reported. A sensitive technique such as differential
      scanning potentiometry was used to determine the pKa constants of the above
      mentioned compounds. In addition, pKa values were calculated from theoretical
      methods, and no significant differences with those of experimental ones were
      observed. X-Ray Powder Diffractometry data demonstrated that compounds 2-4 were
      crystalline while 5 and 6 were amorphous. DSC analysis indicated that all of them
      presented an exothermic decomposition peak above 150  degrees C which is
      accompanied by a weight loss in the respective TG curves. The stability of these
      compounds in aqueous medium at different pH values was investigated, using a
      validated High Performance Liquid Chromatography (HPLC) method, which
      demonstrated to be rapid, selective, sensitive, accurate and stability
      indicating. Good recovery, linearity and precision were also achieved. For all
      compounds the aqueous hydrolysis followed a pseudo-first-order kinetics,
      depending on pH and the union existing between AZT and the associate moiety. The
      hydrolysis was catalyzed by hydroxide ion in the 7.4-13.2 pH range, while all
      compounds exhibited pH-independent stability from acidic to neutral media (pHs
      1.0-7.4).

PMID- 21886899
TI  - Feed forward artificial neural network: tool for early detection of ovarian
      cancer.
AB  - Pathological changes in an organ or tissue may be reflected in proteomic patterns
      in serum. The early detection of cancer is crucial for successful treatment. Some
      cancers affect the concentration of certain molecules in the blood, which allows
      early diagnosis by analyzing the blood mass spectrum. It is possible that
      exclusive serum proteomic patterns could be used to differentiate cancer samples
      from non-cancer ones. Several techniques have been developed for the analysis of
      mass-spectrum curve, and use them for the detection of prostate, ovarian, breast,
      bladder, pancreatic, kidney, liver, and colon cancers. In present study, we
      applied data mining to the diagnosis of ovarian cancer and identified the most
      informative points of the mass-spectrum curve, then used student t-test and
      neural networks to determine the differences between the curves of cancer
      patients and healthy people. Two serum SELDI MS data sets were used in this
      research to identify serum proteomic patterns that distinguish the serum of
      ovarian cancer cases from non-cancer controls. Statistical testing and genetic
      algorithm-based methods are used for feature selection respectively. The results
      showed that (1) data mining techniques can be successfully applied to ovarian
      cancer detection with a reasonably high performance; (2) the discriminatory
      features (proteomic patterns) can be very different from one selection method to
      another.

PMID- 21886900
TI  - Synthesis of Diarylpyrazoles Containing a Phenylsulphone or Carbonitrile Moiety
      and their Chalcones as Possible Anti-Inflammatory Agents.
AB  - A series of chalcone-based diarylpyrazoles containing a phenylsulphone or
      carbonitrile moiety was synthesized. Thus, 3-acetylpyrazoles 6a-c and 10a-c were
      used as useful substrates in facile synthesis of functional pyrazoles 7a-f and
      11a-f, respectively. The anti-inflammatory activity and ulcerogenic effect were
      evaluated and some of the obtained products possessed a significant anti
      inflammatory activity. 1-[1-(3-Methylphenyl)-5-phenyl-4-(phenylsulfonyl)-1H
      pyrazol-3-yl]ethanone (6b) showed a high activity when compared with indomethacin
      as reference drug with lower gastrointestinal (GI) profile. Furthermore,
      molecular docking studies were performed in order to rationalize the obtained
      biological results.

PMID- 21886901
TI  - A Rapid, Stability Indicating RP-UPLC Method for Simultaneous Determination of
      Ambroxol Hydrochloride, Cetirizine Hydrochloride and Antimicrobial Preservatives
      in Liquid Pharmaceutical Formulation.
AB  - A stability indicating reversed phase ultra performance liquid chromatography (RP
      UPLC) method was developed for simultaneous determination of ambroxol
      hydrochloride (AMB), cetirizine hydrochloride (CTZ), methylparaben (MP) and
      propylparaben (PP) in liquid pharmaceutical formulation. The desired
      chromatographic separation was achieved on an Agilent Eclipse plus C18, 1.8 MUm
      (50 * 2.1 mm) column using gradient elution at 237 nm detector wavelength. The
      optimized mobile phase consists of a mixture of 0.01 M phosphate buffer and 0.1 %
      triethylamine as a solvent-A and acetonitrile as a solvent-B. The developed
      method separates AMB, CTZ, MP and PP in presence of twelve known
      impurities/degradation products and one unknown degradation product within 3.5
      min. Stability indicating capability was established by forced degradation
      experiments and seperation of known and unknown degradation products. The lower
      limit of quantification was established for AMB, CTZ, MP and PP. The developed RP
      UPLC method was validated according to the International Conference on
      Harmonization (ICH) guidelines. This validated method is applied for simultaneous
      estimation of AMB, CTZ, MP and PP in commercially available syrup samples.
      Further, the method can be extended for estimation of AMB, CTZ, MP, PP and levo
      cetirizine (LCTZ) in various commercially available dosage forms.

PMID- 21886902
TI  - Validated RP-HPLC Method for Simultaneous Quantitation of Losartan Potassium and
      Metolazone in Bulk Drug and Formulation.
AB  - A HPLC method has been described for simultaneous determination of Losartan
      potassium and Metolazone in formulation. This method is based on a HPLC
      separation of the two drugs on the Thermo Hypersil BDS-C(18) (250 mm * 4.6 mm,
      5.0 MUm) with isocratic conditions and a simple mobile phase containing
      acetonitrile:water (60:40) at a flow rate of 0.8 mL/min using UV detection at 237
      nm. This method has been applied to a marketed formulation without interference
      of excipients. The linear regression analysis data for the calibration plots
      showed a good linear relationship over the concentration range of 2-12 MUg/mL for
      Losartan potassium and 0.2-1.2 MUg/mL for Metolazone, respectively. The method
      was validated for precision, robustness and recovery. Statistical analysis showed
      that the method is repeatable and selective for the estimation of Losartan
      potassium and Metolazone.

PMID- 21886903
TI  - Detection, isolation and characterization of principal synthetic route indicative
      impurities in verapamil hydrochloride.
AB  - Two unknown impurities were detected in verapamil hydrochloride bulk drug using
      isocratic reversed-phase high performance liquid chromatography (HPLC). These
      impurities were isolated by preparative HPLC. Spectral data for the isolated
      impurities were collected. Based on the spectral data derived from two
      dimensional nuclear magnetic resonance (2D-NMR) spectroscopy and mass
      spectrometry (MS), impurity-1 and impurity-2 were characterized as 2-(3,4
      dimethoxyphenyl)-3-methylbut-2-enenitrile and 2-(3,4-dimethoxyphenyl)-2-isopropyl
      3-methylbutanenitrile, respectively.

PMID- 21886904
TI  - Validation of a flow cytometry based binding assay for evaluation of monoclonal
      antibody recognizing EGF receptor.
AB  - An ideal test used to characterize a product must be appropriate for the
      measurement of product quality, manufacturing consistency, product stability, and
      comparability studies. Flow cytometry has been successfully applied to the
      examination of antibodies and receptors on membrane surfaces; however, to date,
      the analytical validation of cytometry based assays is limited. Here we report on
      the validation of a flow cytometry-based assay used in the evaluation of
      nimotuzumab binding to cells over-expressing EGFR on cell surface. The assay was
      validated by examining, assay robustness, specificity, repeatability and
      intermediate precision. The assay was highly specific, robust for all studied
      factors except for cell fixation with 1% paraformaldehyde and met criteria for
      precision with RSD < 2%. In addition the assay has stability-indicating
      properties evidenced by the ability to detect changes in mAb degraded samples.
      Most importantly, the assay demonstrated to be useful for its intended use.

PMID- 21886905
TI  - Development and validation of amisulpride in human plasma by HPLC coupled with
      tandem mass spectrometry and its application to a pharmacokinetic study.
AB  - In this study, authors developed a simple, sensitive and specific liquid
      chromatography-tandem mass spectrometry (LC-MS/MS) method for quantification of
      Amisulpride in human plasma using Amisulpride-d(5) as an internal standard (IS).
      Chromatographic separation was performed on Zorbax Bonus-RP C18, 4.6 * 75 mm, 3.5
      MUm column with an isocratic mobile phase composed of 0.2% formic acid:methanol
      (35:65 v/v), at a flow-rate of 0.5 mL/min. Amisulpride, Amisulpride-d(5) was
      detected at m/z 370.1->242.1 and 375.1->242.1. The drug and the IS were extracted
      by a liquid-liquid extraction method. The method was validated over a linear
      concentration range of 2.0-2500.0 ng/mL for Amisulpride with a correlation
      coefficient of (r(2)) >= 0.9982. This method demonstrated intra- and inter-day
      precision within 0.9 to 1.7 and 1.5 to 2.8 % and intra- and inter-day accuracy
      within 98.3 to 101.5 and 96.0 to 101.0 % for Amisulpride. Amisulpride was found
      to be stable at 3 freeze-thaw cycles, bench top and auto sampler stability
      studies. The developed method was successfully applied to a pharmacokinetic
      study.

PMID- 21886906
TI  - Synthesis, characterization and quantification of simvastatin metabolites and
      impurities.
AB  - Simvastatin is used in treatment of hypercholesterolemia because it regulates
      cholesterol synthesis as a result of its beta-hydroxy acid acting as an inhibitor
      of 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA). The present communication deals
      with synthesis, characterization and development of accurate, precise and
      sensitive Reverse Phase High Performance Liquid Chromatography (RP-HPLC) method
      for simultaneous estimation of simvastatin and its synthetic impurities. The
      impurities methyl ether and beta-hydroxy acid of simvastatin were synthesized in
      the laboratory and characterized by MS, NMR and FT-IR spectroscopy. The
      separation of simvastatin and its impurities was carried out on an isocratic
      JASCO RP-HPLC system using KYA TECH HIQ SIL C(18) column (150 * 4.6 mm internal
      diameter, particle size 5 MUm) operating at ambient temperature using
      acetonitrile:water (80:20 v/v) with 0.1% orthophosphoric acid as mobile phase.
      The method developed for HPLC analysis of three impurities along with simvastatin
      was validated using ICH Q2B (R1) guidelines and it complied with these
      guidelines. The results of analysis were found to be in the range of 98.14% to
      101.89% for all analytes with acceptable accuracy and precision. The method can
      be used for detection and quantification of synthetic impurities in bulk or
      formulations of simvastatin.

PMID- 21886907
TI  - In Vitro and In Vivo Effects of Natural Putative Secretagogues of Glucagon-Like
      Peptide-1 (GLP-1).
AB  - Glucagon-like peptide-1 (GLP-1) is an intestinal hormone with well-established
      glucose-lowering activity. The in vitro and in vivo actions of natural putative
      secretagogues of GLP-1 were investigated. The acute GLP-1 releasing activity of
      olive leaf extract (OLE), glutamine (GLN), alpha casein (ACAS), beta casein
      (BCAS) and chlorogenic acid (CGA) were assessed in STC-1 cells and C57BL/6 mice.
      All compounds except ACAS significantly increased acute in vitro GLP-1 secretion
      (66-386%; P<0.05-0.001). Oral gavage of OLE and GLN modestly increased plasma GLP
      1 concentrations (48% and 41%, respectively), but did not lower glycaemic
      excursions. OLE and GLN are potent stimulators of GLP-1 secretion both in vitro
      and in vivo and chronic studies should assess their suitability as nutritional
      therapies for type 2 diabetes.

PMID- 21886908
TI  - Type 2 Diabetes Mellitus-Induced Hyperglycemia in Patients with NAFLD and Normal
      LFTs: Relationship to Lipid Profile, Oxidative Stress and Pro-Inflammatory
      Cytokines.
AB  - Type 2 diabetes mellitus is associated with dyslipdemia, insulin resistance and
      non alcoholic fatty liver disease. The purpose of the current study was to assess
      whether type 2 diabetes mellitus-induced hyperglycemia has an effect on the lipid
      profile and release of oxidative stress markers and inflammatory mediators in
      patients with non alcoholic fatty liver disease and normal liver function tests
      which may in turn lead to enhancing the pathogenicity of this liver disease. For
      this purpose, one hundred and five outpatients, matched in age and weight, were
      classified into two groups: the first group consisted of patients with non
      alcoholic fatty liver disease and the second group consisted of patients with non
      alcoholic fatty liver disease in conjunction with hyperglycemia due to the
      presence of type 2 diabetes mellitus. In all patients, lipid profile, oxidative
      stress, and inflammatory mediators were assessed by measuring serum
      concentrations of triglycerides, low density lipoprotein, hydrogen preroxide,
      malondialdehyde, tumor necrosis factor-alpha and interleukin-6, respectively. In
      the studied population, it was found that the presence of type 2 diabetes
      mellitus-induced hyperglycemia significantly impaired lipid profile, and
      significantly enhanced the formation of hydrogen preroxide and malondialdehyde as
      well as significantly increased the release of tumor necrosis factor-alpha and
      interleukin-6 in the second group of patients. In addition, plasma glucose level
      showed significant positive correlation with hydrogen peroxide, malondialdehyde,
      tumor necrosis factor-alpha and interleukin-6. From the previous results, it was
      concluded that the presence of type 2 diabetes mellitus-induced hyperglycemia
      results in significant increase in lipid profile, oxidative stress markers and
      inflammatory mediators in patients with non alcoholic fatty liver disease and
      normal liver function tests. For this reason, further research studies may be
      essential to evaluate the benefit of adding suitable antioxidant and anti
      inflammatory drugs to the treatment regimen for this group of patients. In
      addition, regular monitoring of blood glucose levels and liver function tests
      should be advised to this category of patients to reduce liver fat deposition and
      avoid the development of non alcoholic steatohepatitis, cirrhosis or liver cancer
      and their related complications.

PMID- 21886909
TI  - Enhanced antihypertensive activity of candesartan cilexetil nanosuspension:
      formulation, characterization and pharmacodynamic study.
AB  - The objective of the present investigation was to enhance the oral
      bioavailability of practically insoluble Candesartan cilexetil [CC] by preparing
      nanosuspension. The nanosuspension was prepared by media milling using zirconium
      oxide beads and converted to solid state by spray drying. The spray dried
      nanosuspension of CC [SDCN] was evaluated for particle size, zeta potential,
      saturation solubility, crystallanity, surface morphology and dissolution
      behavior. SDCN showed particle size of 223.5+/-5.4 nm and zeta potential of 
      32.2+/-0.6 mV while saturation solubility of bulk CC and SDCN were 125+/-6.9
      MUg/ml and 2805+/-29.5 MUg/ml respectively, showing more than 20 times increase
      in solubility. Differential Scanning Calorimetry [DSC] and X-ray diffraction
      [XRD] analysis showed that crystalline state of CC remained unchanged in SDCN.
      Dissolution studies in phosphate buffer pH 6.5 containing 0.7% Tween 20 showed
      that 53+/-5% of bulk drug dissolved in 15 min whereas SDCN was almost completely
      dissolved exhibiting higher dissolution velocity and solubility. Transmission
      electron microscopy [TEM] revealed that nanocrystals were not of uniform size,
      and approximately of oval shape. Pharmacodynamic study based on
      deoxycorticosterone acetate [DOCA] salt model was performed in rats to evaluate
      in-vivo performance, which showed 26.75+/-0.33% decrease in systolic blood
      pressure for nanosuspension while plain drug suspension showed 16.0+/-0.38%
      reduction, indicating that increase in dissolution velocity and saturation
      solubility leads to enhancement of bioavailability of SDCN when compared to bulk
      CC suspension. Thus, the results conclusively demonstrated a significant
      enhancement in antihypertensive activity of candesartan when formulated as
      nanosuspension.

PMID- 21886910
TI  - Taste masked microspheres of ofloxacin: formulation and evaluation of
      orodispersible tablets.
AB  - Ofloxacin is a synthetic chemotherapeutic antibiotic used for treatment of a
      variety of bacterial infections, but therapy suffers from low patients'
      compliance due to its unpleasant taste. This study was aimed to develop taste
      masked microspheres of ofloxacin using Eudragit and to prepare orodispersible
      tablets of the formulated microspheres using natural superdisintegrant. Taste
      masking Eudragit E100 microspheres were prepared by solvent evaporation technique
      with an entrapment efficiency ranging from 69.54 +/- 1.98 to 86.52 +/- 2.25%. DSC
      revealed no interaction between the drug and polymer. Microspheres prepared at a
      drug/polymer ratio of 1:4 and 1:5 revealed sufficient flow properties and better
      taste masking as compared to other ratios. Drug loaded microspheres were
      formulated as orodispersible tablets using locust bean gum as a natural
      superdisintegrant offering the advatages of biocompatibility and biodegrad
      ability. The wetting time, water absorption ratio and in-vitro disintegration
      time of the tablets were found to range between 19 +/- 2 to 10 +/- 3 seconds,
      59.11 +/- 0.65 to 85.76 +/- 0.96 and 22 +/- 2 to 10 +/- 2 seconds, respectively.
      The in-vitro ofloxacin release was about 97.25% within 2h. The results obtained
      from the study suggested the use of eudragit polymer for preparing ofloxacin
      loaded microspheres with an aim to mask the bitter taste of the drug and
      furthermore orodispersible tablets could be formulated using locust bean gum as a
      natural superdisintegrant.

PMID- 21886912
TI  - The successful relaunch of scientia pharmaceutica continues achieving success.

PMID- 21886911
TI  - Amoxicillin loaded chitosan-alginate polyelectrolyte complex nanoparticles as
      mucopenetrating delivery system for h. Pylori.
AB  - The present study has been undertaken to apply the concept of nanoparticulate
      mucopenetrating drug delivery system for complete eradication of Helicobacter
      pylori (H. pylori), colonised deep into the gastric mucosal lining. Most of the
      existing drug delivery systems have failed on account of either improper
      mucoadhesion or mucopenetration and no dosage form with dual activity of adhesion
      and penetration has been designed till date for treating H. pylori induced
      disorders. In the present study, novel chitosan-alginate polyelectrolyte complex
      (CS-ALG PEC) nanoparticles of amoxicillin have been designed and optimized for
      various variables such as pH and mixing ratio of polymers, concentrations of
      polymers, drug and surfactant, using 3(3) Box-Behnken design. Various studies
      like particle size, surface charge, percent drug entrapment, in-vitro
      mucoadhesion and in-vivo mucopenetration of nanoparticles on rat models were
      conducted. The optimised FITC labelled CS-ALG PEC nanoparticles have shown
      comparative low in-vitro mucoadhesion with respect to plain chitosan
      nanoparticles, but excellent mucopenetration and localization as observed with
      increased fluorescence in gastric mucosa continuously over 6 hours, which
      clinically can help in eradication of H. pylori.

PMID- 21886913
TI  - Pharmacological activation/inhibition of the cannabinoid system affects alcohol
      withdrawal-induced neuronal hypersensitivity to excitotoxic insults.
AB  - Cessation of chronic ethanol consumption can increase the sensitivity of the
      brain to excitotoxic damages. Cannabinoids have been proposed as neuroprotectants
      in different models of neuronal injury, but their effect have never been
      investigated in a context of excitotoxicity after alcohol cessation. Here we
      examined the effects of the pharmacological activation/inhibition of the
      endocannabinoid system in an in vitro model of chronic ethanol exposure and
      withdrawal followed by an excitotoxic challenge. Ethanol withdrawal increased N
      methyl-D-aspartate (NMDA)-evoked neuronal death, probably by altering the ratio
      between GluN2A and GluN2B NMDA receptor subunits. The stimulation of the
      endocannabinoid system with the cannabinoid agonist HU-210 decreased NMDA-induced
      neuronal death exclusively in ethanol-withdrawn neurons. This neuroprotection
      could be explained by a decrease in NMDA-stimulated calcium influx after the
      administration of HU-210, found exclusively in ethanol-withdrawn neurons. By
      contrast, the inhibition of the cannabinoid system with the CB1 receptor
      antagonist rimonabant (SR141716) during ethanol withdrawal increased death of
      ethanol-withdrawn neurons without any modification of NMDA-stimulated calcium
      influx. Moreover, chronic administration of rimonabant increased NMDA-stimulated
      toxicity not only in withdrawn neurons, but also in control neurons. In summary,
      we show for the first time that the stimulation of the endocannabinoid system is
      protective against the hyperexcitability developed during alcohol withdrawal. By
      contrast, the blockade of the endocannabinoid system is highly counterproductive
      during alcohol withdrawal.

PMID- 21886914
TI  - Nutritional asymmetries are related to division of labor in a queenless ant.
AB  - Eusocial species exhibit pronounced division of labor, most notably between
      reproductive and non-reproductive castes, but also within non-reproductive castes
      via morphological specialization and temporal polyethism. For species with
      distinct worker and queen castes, age-related differences in behavior among
      workers (e.g. within-nest tasks versus foraging) appear to result from
      physiological changes such as decreased lipid content. However, we know little
      about how labor is divided among individuals in species that lack a distinct
      queen caste. In this study, we investigated how fat storage varied among
      individuals in a species of ant (Dinoponera australis) that lacks a distinct
      queen caste and in which all individuals are morphologically similar and capable
      of reproduction (totipotent at birth). We distinguish between two hypotheses, 1)
      all individuals are physiologically similar, consistent with the possibility that
      any non-reproductive may eventually become reproductive, and 2) non-reproductive
      individuals vary in stored fat, similar to highly eusocial species, where
      depletion is associated with foraging and non-reproductives have lower lipid
      stores than reproducing individuals. Our data support the latter hypothesis.
      Location in the nest, the probability of foraging, and foraging effort, were all
      associated with decreased fat storage.

PMID- 21886915
TI  - A sample-saving method for heat capacity measurements on powders using relaxation
      calorimetry.
AB  - An experimental method is described for determining the low-temperature heat
      capacity (C(p)) of mg-sized powder samples using the Quantum Design "Physical
      Properties Measurement System" (PPMS). The powder is contained in an Al pan as an
      ~1 mm thick compressed layer. The sample is not mixed with Apiezon N grease, as
      compared to other methods. Thus, it is not contaminated and can be used for
      further study. This is necessary for samples that are only available in tiny
      amounts. To demonstrate the method various samples, all insulating in nature,
      were studied including benzoic acid, sapphire and different silicate minerals.
      The measurements show that the method has an accuracy in C(p) to better than 1%
      at T above 30-50 K and +/-3-5% up to +/-10% below. The experimental procedure is
      based on three independent PPMS and three independent differential scanning
      calorimetry (DSC) measurements. The DSC C(p) data are used to slightly adjust the
      PPMS C(p) data by a factor CpDSC/CpPPMSat298K. This is done because heat
      capacities measured with a DSC device are more accurate around ambient T (?0.6%)
      than PPMS values and is possible because the deviation of PPMS heat capacities
      from reference values is nearly constant between about 50 K and 300 K. The
      resulting standard entropies agree with published reference values within 0.21%
      for the silicates, by 0.34% for corundum, and by 0.9% for powdered benzoic acid.
      The method thus allows entropy determinations on powders with an accuracy of
      better than 1%. The advantage of our method compared to other experimental
      techniques is that the sample powder is not contaminated with grease and that
      heat capacity values show less scatter at high temperatures.

PMID- 21886916
TI  - Art and science of Orthopedics.

PMID- 21886917
TI  - The 3-min appraisal of a diagnostic test.

PMID- 21886918
TI  - Aperture in coronoid-olecranon septum: A radiological evaluation.
AB  - BACKGROUND: The humerus bone with coronoid-olecranon septal aperture have very
      narrow medullary canal and extreme anterolateral bowing proximally and/or extreme
      anterolateral compressed surface at distal part. Septal perforation might make
      nailing through a retrograde technique more difficult or possibly with an
      increased risk of iatrogenic fracture at the site of insertion. Coronoid
      olecranon perforation might be very important in preoperative planning for
      successful nailing. Since the data available has been obtained from the ancient
      studies using the skeletal material, the present study is aimed at investigating
      originally the presence of the coronoid-olecranon septum perforation in the
      living subjects, using a radiographic method. MATERIALS AND METHODS: The study
      was performed on direct radiograms and computed tomography of the elbow obtained
      from the 709 volunteers (367 males, 342 females). RESULTS: The incidence of the
      perforation was found to be 8.6 %. Bilateral occurrence was found to be more
      common significantly. The highest incidence occurred in second decade.
      CONCLUSION: The present study suggests female prepronounced and left asymmetry in
      case of septal perforation. Bilateral occurrence from our study might be peculiar
      to the clinician.

PMID- 21886919
TI  - Spinaplasty following lumbar laminectomy for multilevel lumbar spinal stenosis to
      prevent iatrogenic instability.
AB  - BACKGROUND: Iatrogenic instability following laminectomy occurs in patients with
      degenerative lumbar canal stenosis. Long segment fusions to obviate postoperative
      instability result in loss of motion of lumbar spine and predisposes to adjacent
      level degeneration. The best alternative would be an adequate decompressive
      laminectomy with a nonfusion technique of preserving the posterior ligament
      complex integrity. We report a retrospective analysis of multilevel lumbar canal
      stenosis that were operated for posterior decompression and underwent spinaplasty
      to preserve posterior ligament complex integrity for outcome of decompression and
      iatrogenic instability. MATERIALS AND METHODS: 610 patients of degenerative
      lumbar canal stenosis (n=520) and development spinal canal stenosis (n=90), with
      a mean age 58 years (33-85 years), underwent multilevel laminectomies and
      spinaplasty procedure. At followup, changes in the posture while walking,
      increase in the walking distance, improvement in the dysesthesia in lower limb,
      the motor power, capability to negotiate stairs and sphincter function were
      assessed. Forward excursion of vertebrae more than 4 mm in flexion-extension
      lateral X-ray of the spine as compared to the preoperative movements was
      considered as the iatrogenic instability. Clinical assessment was done in
      standing posture regarding active flexion-extension movement, lateral bending and
      rotations RESULTS: All patients were followed up from 3 to 10 years. None of the
      patients had neurological deterioration or pain or catch while movement. Walking
      distance improved by 5-10 times, with marked relief (70-90%) in neurogenic
      claudication and preoperative stooping posture, with improvement in sensation and
      motor power. There was no significant difference in the sagittal alignment as
      well as anterior translation. Two patients with concomitant scoliosis and one
      with cauda equine syndrome had incomplete recovery. Two patients who developed
      disc protrusion, underwent a second operation for a symptomatic disc prolapse.
      CONCLUSION: Spinaplasty following posterior decompression for multilevel lumbar
      canal stenosis is a simple operation, without any serious complications,
      retaining median structures, maintaining the tension band and the strength with
      least disturbance of kinematics, mobility, stability and lordosis of the lumbar
      spine.

PMID- 21886921
TI  - Intramedullary fixation of forearm fractures with new locked nail.
AB  - BACKGROUND: Lack of availability of interlocked nails made plate osteosynthesis
      the first choice of treatment of forearm fractures inspite of more surgical
      exposure, periosteal stripping and big skin incision subsequent scar along with
      higher risk of refracture on implant removal. We hereby report the first 12 cases
      with 19 forearm bone fractures internally fixed by indegenous interlocked nail.
      MATERIALS AND METHODS: Existing square nails were modified to have a broad
      proximal end of 5.5 mm with a hole for locking screw of 2.5 mm. The nail has a
      distal hole of 1/1.2/1.5 mm in 2.5/3/3.5 mm diameter nail, respectively. A new
      method of distal locking with a clip made of k wire is designed. The clip after
      insertion into the bone and hole in nail and opposite cortex snuggly fits the
      bone providing a secure locking system. Twelve skeletally mature patients, mean
      age 32 years (range 24-45 years) with 19 diaphyseal fractures of the forearm were
      treated with this indigenously made new nail. The patient were evaluated for
      fracture union, functional recovery and complications. The functional outcome was
      assessed by disabilities of arm, shoulder and hand questionnaire (DASH score).
      RESULTS: Time to radiographic union ranged between 12 and 28 weeks, with a 100%
      union rate. Complications were minimal, with mild infection in open fracture
      (n=1) and delayed union (n=1) in patient with comminuted fracture of the ulna
      only. The clinical results were excellent. The DASH score ranged between 0 and 36
      points. CONCLUSION: This new interlocking nail may be considered as an
      alternative to plate osteosynthesis for fractures of the forearm in adults. The
      advantages are benefit of closed reduction, smaller residual scar, reduced cost
      and early union with allowance of immediate movements.

PMID- 21886920
TI  - Outcome of radial head preserving operations in missed Monteggia fracture in
      children.
AB  - BACKGROUND: The dislocated radial head in missed Monteggia fracture loses its
      concave articular surface and displays hypertrophic changes and flattened humeral
      capitellum configuration, thereby limiting the range of motion. We evaluated the
      results of open reduction in missed Monteggia fractures by various techniques.
      MATERIALS AND METHODS: Sixty-three missed Monteggia fractures were included in
      the analysis. We performed four combinations of operation: Group I: 22 patients
      treated with modified Hirayama ulnar osteotomy plus annular ligament
      reconstruction with free Palmaris longus grafting; Group II:18 patients treated
      with modified Hirayama ulnar osteotomy plus annular ligament reconstruction by
      the Bell Tawse's procedure; Group III-9: patients treated with only modified
      Hirayama's osteotomy; and Group IV: 14 patients treated with transverse osteotomy
      of ulna and annular ligament reconstruction by the Bell Tawse's procedure. During
      followup these cases were assessed for the following parameters: 1) range of
      motion and 2) mayo elbow performance index (MEPI). Results were noted on follow
      ups at 3, 6, 12 months and then on yearly basis. Sixty-three patients were
      followed up for an average duration of 5.6 years (range 3-8 years). RESULTS: The
      mean range of motion was increased by 45 degrees , 30 degrees , 45 degrees , 20
      degrees  for Group I, II, III and IV respectively. The average increase in MEPI
      scores was also almost on the same lines. There was one case of frank dislocation
      in group III and six cases of subluxation, two each in Groups II, III, and IV.
      For Annular ligament reconstruction, amongst two procedures, Groups II and IV
      (Bell Tawse group), had a significant extension lag contributing to the lower
      increase in the range of motion as compared to the Palmaris longus reconstruction
      group (group I). CONCLUSION: Hirayama's osteotomy is inherently more stable than
      the simple transverse osteotomy and it should be combined with annular ligament
      reconstruction. Palmaris longus graft for ligament reconstruction provides more
      stability as compare to Bell Towse's procedure.

PMID- 21886922
TI  - Internal fixation of fractures of both bones forearm: Comparison of locked
      compression and limited contact dynamic compression plate.
AB  - BACKGROUND: The locking compression plate (LCP) with combination holes is a newer
      device in fracture fixation. We undertook a study comparing the LCP with limited
      contact dynamic compression plate (LC-DCP) in the treatment of diaphyseal
      fractures of both bones of the forearm. MATERIALS AND METHODS: This is a
      prospective comparative study, 36 patients (18 in each group) with fractures of
      both the forearm bones (72 fractures) were treated with one of the two devices.
      The average age of the patients was 30.5 years (range 16-60 years) with mean
      followup of 2.1 years (range 1.5-2.8 years). The patients were assessed for
      fracture union and function and complications and by Disabilities of the Arm,
      Shoulder and Hand (DASH) score for patient related outcome at the latest
      followup. RESULTS: There was no significant difference in two groups with respect
      to the range of movements or grip strength. One case had delayed union (LC-DCP
      group) and another had synostosis (LCP group). Plate removal was done in four
      cases within the study period with no refracture till the presentation of this
      report. CONCLUSION: LC plating is an effective treatment option for fractures of
      both bones of forearm. The present study could not prove its superiority over LC
      DCP.

PMID- 21886923
TI  - Percutaneous pinning for non-comminuted extra-articular fractures of distal
      radius.
AB  - BACKGROUND: Various treatment modalities have been described for the treatment of
      extra-articular distal radius fractures each with its own merits and demerits.
      Most of the work done with percutaneous pinning has shown a significant residual
      stiffness of the hand and wrist. Our technique involves percutaneous pinning of
      the fracture and immobilization in neutral position of the wrist for three weeks.
      This study's aim was to examine the functional outcome of percutaneous K-wiring
      of these extra-articular distal radius fractures with immobilization in neutral
      position of the wrist. MATERIALS AND METHODS: This is a prospective study of 32
      patients aged between 18 and 70 years with extra-articular distal radius
      fracture. Patients were treated with closed reduction and percutaneous pinning
      using two or three K-wires. A below- elbow plaster of paris dorsoradial slab was
      applied in neutral position of the wrist for 3 weeks. At the end of 3 weeks, the
      slab was removed and wrist physiotherapy started. The radiographs were taken
      postoperatively, at 3 weeks, 6 weeks and 6 months. The functional evaluation of
      the patients was done at 6 months follow-up. We used Sarmiento's modification of
      Lindstrom criteria and Gartland and Werley's criteria for evaluation of results.
      RESULTS: Excellent to good results were seen in 93.75% of the cases while 6.25%
      had fair results. The complications observed were pin loosening (n=13), pin tract
      infection (n=2), malunion (n=2), wrist joint stiffness (n=2), reduced grip
      strength (n=2) and injury to the superficial radial nerve (n=1). CONCLUSION:
      Percutaneous pinning followed by immobilization of the wrist in neutral position
      is a simple and effective method to maintain reduction and prevent stiffness of
      wrist and hand.

PMID- 21886924
TI  - Functional outcome of neglected perilunate dislocations treated with open
      reduction and internal fixation.
AB  - INTRODUCTION: Management of neglected perilunate dislocations is controversial.
      The various procedures such as open reduction and internal fixation (ORIF),
      proximal row carpectomy, lunate excision, and wrist arthrodesis have been
      advocated. The aim of our study was to evaluate the functional outcome of
      neglected perilunate dislocations managed by ORIF. MATERIALS AND METHODS: Over a
      period of 10 years (1996 to 2006), 14 patients with neglected perilunate
      dislocations (undiagnosed or untreated for 6 weeks or more) were managed by ORIF.
      Six patients had dorsal trans-scaphoid perilunate dislocation, 6 patients had
      volar lunate dislocation while the remaining two had a dorsal perilunate
      dislocation The results were evaluated by clinical scoring system of Cooney et
      al. RESULTS: The average followup was 4.1 years (range 2-12 years). All except
      one of the patients operated earlier than 5 months had good results. Of the four
      patients operated after 5 months, two had a fair result while two had a poor
      outcome. Chondral damage to the capitate was noted intraoperatively in both the
      cases with poor outcomes. The two patients were found to have avascular necrosis
      (AVN) of the lunate; however, functional outcome was fair in both, and both were
      able to return to their profession. CONCLUSION: We observed favorable functional
      results of ORIF in neglected perilunate dislocations up to 5 months after injury.
      The development of AVN or midcarpal arthritis was not a major disabling factor as
      long as stability of wrist has been restored. Beyond 5 months, an alternative
      surgical procedure such as proximal row carpectomy should be contemplated as
      results of ORIF have not been good uniformly.

PMID- 21886925
TI  - Outcome of closed proximal phalangeal fractures of the hand.
AB  - BACKGROUND: The proximal phalanx (PP) of the fingers is fractured more frequently
      than the middle or even distal phalanges. The problems of malunion, stiffness and
      sometimes loss of skin or other soft tissues associated with PP fracture
      increases the disability. The optimum treatment depends on fracture location,
      fracture geometry and fracture stability. The objective of the study was to
      analyse the treatment outcome in a series of closed proximal phalangeal fractures
      of the hand. MATERIALS AND METHODS: Eighty-four proximal phalangeal fractures in
      68 patients were enrolled from 2007 to 2009. The treatment modalities were
      broadly categorised into two groups, Group A consisted of conservative treatment,
      and Group B consisted of surgical treatment. Group A included 47 digits treated
      with closed reduction (CR) with immobilization (n=43), extension block cast and
      dynamic traction (n=4), while 37 digits were treated in Group B, which included
      closed or open reduction (OR) and internal fixation (IF) with K-wires (n=31), OR
      and IF with stainless-steel wiring (n=2), and mini external-fixator (n=4).
      Belsky's criteria and Gingrass' criteria were used for assessment of finger
      injuries and to assess the efficacy of conservative and surgical modalities for
      closed proximal phalangeal fractures of the hand. RESULTS: Average period of
      follow-up was 1 year (range 10-14 months). The excellent to good results seen in
      Groups A and B were 89% and 92%, respectively. Six complications were seen in
      Group A, which included four cases with malunion and two cases with digital
      stiffness. Three complications were seen in Group B, which included one each of
      malunion, digital stiffness and extensor lag. Overall, maximum poor results (n=4)
      were seen with CR and buddy strapping. CONCLUSION: Conservative treatment is an
      inexpensive method, particularly suitable for stable fractures, and in patients
      who are poor candidates for surgery, Surgical modalities have distinct advantage
      of stable fixation, but with added risk of digital stiffness. Percutaneous
      pinning is a reliable, most commonly used surgical modality and technically
      easier. Both conservative and surgical modalities have good efficacy when used
      judiciously.

PMID- 21886926
TI  - Medium term results of Avon patellofemoral joint replacement.
AB  - BACKGROUND: Ten to fifteen percent of knee arthritis is reported to be isolated
      patellofemoral arthritis. Total knee arthroplasty is not recommended for isolated
      patella femoral arthritis particularly in young patients. We present the
      retrospective review of 45 consecutive patellofemoral replacements performed in
      41 such patients, between June 2002 and January 2007. MATERIALS AND METHODS: All
      patients were operated by single surgeon (SM) or under his supervision. All forty
      five patients had minimum three year followup and had the data collected
      prospectively. No patient was lost to followup. This data was later collated by
      review of notes, radiographs, and a clinical followup. The patients were assessed
      using knee function score and Melbourne patellofemoral score. RESULTS: The
      average followup was 4.5 years. The preoperative average Melbourne (Bartlett)
      score was 10 (range 5-21). Preoperative knee functional score averaged 57 (range
      23-95). The average range of movement was 116 degrees  (range 100 degrees -140
      degrees ). Postoperatively, the average Melbourne knee score improved to 25
      (range 11-30), while the knee function score was 85 (range 28 - 100). The
      difference was statistically significant (P<0.05). Eighty-five percent rated the
      result as good or excellent, while 12% rated it as fair. Five percent thought the
      result was poor. The most common complaint was clicking at 40 degrees  of flexion
      (n=7). Six patients underwent arthroscopic lateral release, which improved the
      symptoms in four patients. Two knees were revised one due to progression of
      tibiofemoral arthritis and the other due to persistent clicking, yielding a
      survival rate of 95.6% at an average five year followup. CONCLUSION: The Avon
      patellofemoral joint replacement provides predictably good results and excellent
      survivorship in the medium term, for isolated patellofemoral arthritis. However,
      progression of tibiofemoral arthritis remains unpredictable and therefore patient
      selection is crucial to ensure success. Clicking remains a potential problem and
      can compromise the postoperative results in upto 15% of the cases.

PMID- 21886927
TI  - Midterm results of biologic fixation or mosaicplasty and drilling in
      osteochondritis dissecans.
AB  - BACKGROUND: Osteochondritis dissecans (OCD) primarily affects subchondral bone.
      Multiple drilling, fixation implant or autogenous osteochondral grafts are
      reported as treatment options. We present the midterm results of cases in which
      an OCD lesion was treated by osteochondral autograft transfer and drilling.
      MATERIALS AND METHODS: Between 2002 and 2006, 14 knees with International
      Cartilage Repair Society (ICRS-OCD) type II and III lesions were treated in our
      clinic using osteochondral autograft transfer and drilling by arthroscopic or
      open surgery. The average age of our patients was 22.14 years (range 17-29 years)
      and average followup was of 24.3 months (range 11-40 months). Lesion type was
      ICRS type II in five patients (35.7%) and ICRS type III in nine patients (64.3%).
      In cases with ICRS-OCD type II lesions, in situ fixation was applied following
      circumferential multiple drilling, while mosaicplasty was done following
      debridement and multiple drilling in cases with ICRS-OCD type III lesion.
      Mosaicplasty was performed in the lesion area by an average of 2.5 (range 1-3)
      cylindrical osteochondral autografts. Patients were not allowed to perform
      loading activities for 3 weeks in the postoperative period; movement was
      initiated by using CPM device in the early phase; full range of motion was
      achieved in third week, and full weight bearing was permitted in 6 to 8 weeks
      RESULTS: While 6 and 8 patients were classified preoperatively as fair and poor,
      respectively, according to Hughston scale, excellent and good results were
      obtained postoperatively in 10 and 4 patients, respectively. During the followup,
      no problems were detected in any of the patients in the regions where
      osteochondral graft was harvested. CONCLUSION: Biologic fixation or mosaicplasty
      and drilling as a technique to treatment of the lesion in OCD by osteochondral
      autograft transfer has resulted in good and excellent clinical outcomes in our
      patients and it is considered that providing blood flow to subchondral bone by
      circumferencial drilling leads to an increase in the robustness of biological
      internal fixation and shortens the duration of recovery.

PMID- 21886928
TI  - Deep vein thrombosis and thromboprophylaxis in arthroscopic anterior cruciate
      ligament reconstruction.
AB  - BACKGROUND: There is no clear evidence in the literature regarding the incidence
      of deep vein thrombosis (DVT) in patients undergoing arthroscopic anterior
      cruciate ligament (ACL) reconstruction. Literature also lacks on the
      recommendations on thromboprophylaxis in patients undergoing elective
      arthroscopic ACL reconstruction. We conducted a prospective analysis to assess
      incidence of DVT in patients undergoing arthroscopic ACL reconstruction.
      MATERIALS AND METHODS: 120 consecutive patients with MRI proven ACL injury who
      were operated for arthroscopic ACL reconstruction were enrolled in this
      prospective study. None of the patients had risk factors (on history) for DVT,
      and all were below the age of 45 years. All cases were operated upon by a single
      surgeon and a standard rehabilitation regime was followed. The patients underwent
      clinical examination and screening (Doppler ultrasonography/venous scan) for any
      DVT, on the day prior to surgery, day of discharge (Day 3) and at 4 weeks
      postsurgery. None of the patients received any form of thromboprophylaxis against
      DVT. RESULTS: One hundred and twelve patients (61 males and 51 females) completed
      the study. The average age was 31.6 years (range 24-42 years). All patients
      underwent arthroscopic assisted ACL reconstruction surgery within 3 weeks of the
      injury. Two patients (males) in the series had Doppler venous scan proven DVT.
      One patient was asymptomatic but the screening Doppler picked up the DVT on the
      third postoperative day. The other patient was symptomatic at 12 weeks with pain
      and swelling in the leg and had ultrasound -proven DVT. CONCLUSION: In our study
      the incidence of deep vein thrombosis in patients undergoing arthroscopic ACL
      reconstruction is 1.78%. We do not recommend routine thromboprophylaxis in
      patients, who are not high risk candidates for thrombosis and are of less than 45
      years, in patients undergoing arthroscopic ACL reconstruction, with early
      postoperative rehabilitation.

PMID- 21886929
TI  - Evaluation of the syndesmotic-only fixation for Weber-C ankle fractures with
      syndesmotic injury.
AB  - BACKGROUND: With the length of the fibula restored and the syndesmosis reduced
      anatomically, internal fixation using a plating device may not be necessary for
      supra-syndesmotic fibular fractures combined with diastasis of inferior tibio
      fibular joint. A retrospective observational study was performed in patients who
      had this injury pattern treated with syndesmosis-only fixation. MATERIALS AND
      METHODS: 12 patients who had Weber type-C injury pattern were treated with
      syndesmosis only fixation. The treatment plan was followed only if the fibular
      length could be restored and if the syndesmosis could be anatomically reduced.
      Through a percutaneous or mini-open reduction and clamp stabilization of the
      syndesmosis, all but one patient had a single tricortical screw fixation across
      the syndesmosis. Patients were kept non-weight-bearing for 6 weeks, followed by
      screw removal at an average of 8 weeks. Outcomes were assessed using an objective
      ankle scoring system (Olerud and Molander scale) and by radiographic assessment
      of the ankle mortise. RESULTS: At a mean follow-up of 13 months, the functional
      outcome score was 75. Excellent to good outcomes were noted in 83% of the
      patients. Ankle mortise was reduced in all cases, and all but one fibular
      fracture united without loss of fixation. Six patients had more than one
      malleolar injury, needing either screw or anchor fixations. One patient had late
      diastasis after removal of the syndesmotic screw and underwent revision surgery
      with bone grafting of the fibula. This was probably due to early screw removal,
      before union of the fibular fracture had occurred. CONCLUSION: We recommend
      syndesmosis-only fixation as an effective treatment option for a combination of
      syndesmosis disruption and Weber type-C lateral malleolar fractures.

PMID- 21886930
TI  - Management of thromboangiitis obliterans using distraction osteogenesis: A
      retrospective study.
AB  - BACKGROUND: Thromboangiitis obliterans (TAO), also known as Buerger disease, is
      characterized by thrombosis in medium-sized arteries and veins along with a
      marked inflammatory response. TAO can be managed by using the principle of
      distraction osteogenesis to induce neoangiogenesis. We report thirty patients of
      TAO in the age-group of 20-50 years were treated with the Ilizarov method.
      MATERIALS AND METHODS: Patients with severe rest pain (n=30), absent distal
      pulsation (n=30) and ulcer (n=6) and/or gangrene of the toes (n=4), who had
      failed the conservative pharmacological modalities of treatment were included. A
      lateral tibial corticotomy was performed and distraction applied by use of olive
      wire. A two-ring frame was used for all cases. RESULTS: Of the 30 cases, 25
      patients became pain free while 1 had partial relief of pain. The four patients
      worsened on treatment and developed frank infection were amputed. The average
      distraction was 1.8+/-0.3 mm (range: 1.5-2.2 cm). The mean consolidation period
      was 98+/-11 days, after which the fixator was removed. The total duration of
      treatment was 122+/-23 days. There were two cases of osteomyelitis in our series;
      both healed after debridement and both patients had good result, with relief of
      pain. The ulcers started healing by 4-6 weeks. CONCLUSION: The principle of the
      distraction osteogenesis including neoangiogenesis can be used for treatment of
      TAO and has an acceptable complication rate.

PMID- 21886931
TI  - Computer navigation assisted fixation in neglected C2-C3 dislocation in an adult.
AB  - A 49-year-old male presented with neck pain and deformity following an industrial
      accident sustained two months back. His neurology was normal except for a minimal
      weakness in left biceps (grade 4/5). Radiographs, magnetic resonance imaging and
      computed tomographic scan revealed fracture dislocation of C2-C3 with significant
      lateral translation of C2 over C3 without disc herniation. In view of
      unsuccessful closed reduction and absent disc herniation at the level of
      dislocation, a posterior only reduction, stabilisation and fusion with Iso-C 3D
      computer navigation-assisted cervical pedicle screw fixation with transverse rod
      screw construct was performed. At 6 months followup the patient was completely
      relieved of his symptoms and was able to return to his previous occupation. The
      rare case is reported for the management by Iso-C 3D computer navigation assisted
      cervical pedicle screw fixation and reduction with transverse rod-screw construct
      at each involved level.

PMID- 21886932
TI  - Atlantoaxial arthrodesis using C1-C2 transarticular screw fixation in a case of
      Morquio syndrome.
AB  - Prophylactic or therapeutic arthrodesis is recommended for atlantoaxial
      instability in Morquio syndrome. Occipitocervical fusion, the common approach for
      upper cervical fusion in Morquio syndrome sacrifices the movements at the
      occipitoatlantal joints. The use of C1-C2 transarticular screws for achieving C1
      C2 arthrodesis, without compromising mobility at the occipitoatlantal joint in
      Morquio syndrome has not been reported. We report a case of Morquio syndrome with
      atlantoaxial instability and odontoid hypoplasia, where we successfully achieved
      C1-C2 arthrodesis using transarticular screws and bone graft. The advantages of
      this method over other methods of atlantoaxial arthrodesis in Morquio syndrome
      have also been discussed.

PMID- 21886933
TI  - Radial nerve entrapement in osseous tunnel without clinical symptoms.
AB  - Entrapment of a nerve in the callus of a healing fracture is not a common entity,
      but it does exist. The entrapment usually presents without neurological deficit.
      It is difficult to suspect the radial nerve injury if we need to operate on the
      same site. We present a case of entrapment of radial nerve in the callus of a
      supracondylar humerus fracture with cubitus varus deformity. The surgery for
      correction of the deformity led to the damage of the nerve. In retrospect a
      careful assessment of the x-rays showed two 3-4 mm diameter holes. Awareness of
      this finding would have given us sufficient indication of nerve entrapment to
      prevent this mishap.

PMID- 21886934
TI  - Giant cell tumor of the metacarpal bones.
AB  - Giant cell tumor (GCT) of hand bones is rare. We present two cases of GCT of
      metacarpal bone. One case was treated successfully with ray amputation. The
      second patient underwent wide resection and tricortical iliac crest bone
      grafting. Till the last follow-up (at 26 and 70 months respectively) both
      patients have been recurrence free and have returned to their previous
      occupational activities.

PMID- 21886935
TI  - Forearm gangrene following distraction injury at elbow in a neonate.
AB  - Gangrene of limbs in newborn is extremely rare. A number of aetiological factors
      may account for such type of situation. We describe herewith a case of gangrene
      of forearm in newborn following distraction injury to the physis of elbow and
      vessels of forearm by excessive pull on upper limb during difficult delivery.

PMID- 21886936
TI  - The separate or combined evaluation of co-morbidities have a different effect on
      the role of surgical delay on 1 year mortality.

PMID- 21886937
TI  - Authors' reply.

PMID- 21886938
TI  - Comment on "Tranexamic acid for control of blood loss in bilateral total knee
      replacement in a single stage".

PMID- 21886939
TI  - Authors' reply.

PMID- 21886940
TI  - Depth-Encoded Spectral Domain Phase Microscopy for Simultaneous Multi-Site
      Nanoscale Optical Measurements.
AB  - Spectral domain phase microscopy (SDPM) is an extension of spectral domain
      optical coherence tomography (SDOCT) that exploits the extraordinary phase
      stability of spectrometer-based systems with common-path geometry to resolve sub
      wavelength displacements within a sample volume. This technique has been
      implemented for high resolution axial displacement and velocity measurements in
      biological samples, but since axial displacement information is acquired serially
      along the lateral dimension, it has been unable to measure fast temporal dynamics
      in extended samples. Depth-Encoded SDPM (DESDPM) uses multiple sample arms with
      unevenly spaced common path reference reflectors to multiplex independent SDPM
      signals from separate lateral positions on a sample simultaneously using a single
      interferometer, thereby reducing the time required to detect unique optical
      events to the integration period of the detector. Here, we introduce DESDPM and
      demonstrate the ability to acquire useful phase data concurrently at two
      laterally separated locations in a phantom sample as well as a biological
      preparation of spontaneously beating chick cardiomyocytes. DESDPM may be a useful
      tool for imaging fast cellular phenomena such as nervous conduction velocity or
      contractile motion.

PMID- 21886941
TI  - Synthetic Studies Toward Providencin: Efficient Construction of a Furanyl
      Cyclobutanone Fragment.
AB  - Described is the construction of a furanyl-cylcobutanone fragment suited for
      incorporation into a synthesis of the naturally occurring anti-cancer agent
      Providencin.

PMID- 21886942
TI  - Forward-Thinking Teens: The Effects of College Costs on Adolescent Risky
      Behavior.
AB  - This paper analyzes the effect of college costs on teenagers' engagement in risky
      behaviors before they are old enough to attend college. Individuals with brighter
      prospects for future schooling attainment may engage in less drug and alcohol use
      and risky sexual activity because they have more to lose if such behaviors have
      harmful effects in their lives. If teens correctly predict that higher college
      costs make future college enrollment less likely, then adolescents facing
      different expected costs may choose different levels of risky behavior. I find
      that lower college costs in teenagers' states of residence raise their subjective
      expectations regarding college attendance and deter teenage substance use and
      sexual partnership. Specifically, a $1,000 reduction in tuition and fees at two
      year colleges in a youth's state of residence (roughly a 50% difference at the
      mean) is associated with a decline in the number of sexual partners the youth had
      in the past year (by 26%), the number of days in the past month the youth smoked
      (by 14%), and the number of days in the past month the youth used marijuana (by
      23%). These findings suggest that the often-studied correlation between schooling
      and health habits emerges in adolescence because teenagers with brighter college
      prospects curb their risky behavior in accordance with their expectations. The
      results also imply that policies that improve teenagers' educational prospects
      may be effective tools for reducing youthful involvement in such behaviors.

PMID- 21886943
TI  - Brief Intervention for Emergency Department Patients with Alcohol Misuse:
      Implications for Current Practice.
AB  - This article reviews studies and current practices of brief motivational
      intervention in the emergency department and identifies factors related to the
      effectiveness of brief intervention. Studies of brief intervention in the
      emergency department have had mixed results with most studies showing
      improvements in both intervention and control groups. Most report brief
      intervention reducing alcohol's negative consequences without reducing
      consumption. Clinical practice is incorporating brief intervention as part of
      emergency treatment and further research is needed to determine the factors most
      responsible for the improvements noted in most studies.

PMID- 21886944
TI  - MEMS Sensors and Microsystems for Cell Mechanobiology.
AB  - Forces generated by cells play a vital role in many cellular processes like cell
      spreading, motility, differentiation and apoptosis. Understanding the mechanics
      of single cells is essential to delineate the link between cellular force
      generation/sensing and function. MEMS sensors, because of their small size and
      fine force/displacement resolution, are ideal for force and displacement sensing
      at the single cell level. In addition, the amenability of MEMS sensors to batch
      fabrication methods allows the study of large cell populations simultaneously,
      leading to robust statistical studies. In this review, we discuss various
      microsystems used for studying cell mechanics and the insights on cell mechanical
      behavior that have resulted from their use. The advantages and limitations of
      these microsystems for biological studies are also outlined.

PMID- 21886945
TI  - Development of Microfabricated Magnetic Actuators for Removing Cellular
      Occlusion.
AB  - Here we report on the development of torsional magnetic microactuators for
      displacing biological materials in implantable catheters. Static and dynamic
      behaviors of the devices were characterized in air and in fluid using optical
      experimental methods. The devices were capable of achieving large deflections
      (>60 degrees ) and had resonant frequencies that ranged from 70 Hz to 1.5 kHz in
      fluid. The effect of long-term actuation (>2.5 . 10(8) cycles) was quantified
      using resonant shift as the metric (Deltaf < 2%). Cell-clearing capabilities of
      the devices were evaluated by examining the effect of actuation on a layer of
      aggressively growing adherent cells. On average, actuated microdevices removed
      37.4% of the adherent cell layer grown over the actuator surface. The effect of
      actuation time, deflection angle, and beam geometry were evaluated. The
      experimental results indicate that physical removal of adherent cells at the
      microscale is feasible using magnetic microactuation.

PMID- 21886946
TI  - Can his research become my publication?

PMID- 21886947
TI  - Management of tuberculosis: From drug treatment to control program.

PMID- 21886948
TI  - Evaluation of revised national tuberculosis control program, district Kangra,
      Himachal Pradesh, India, 2007.
AB  - BACKGROUND: THE PRESENT EVALUATION STUDY HAS BEEN CONDUCTED WITH THE FOLLOWING
      OBJECTIVES: (i) To assess the treatment outcomes of revised national tuberculosis
      control program (RNTCP) in five microscopic centers of Kangra district under five
      tuberculosis units and (ii) To identify gaps and underlying contributing factors.
      Based upon the findings of (i) and (ii) we suggest appropriate measures to narrow
      down the existing gaps. MATERIALS AND METHODS: We identified and interviewed
      health personnel involved, reviewed the documents and records pertaining to
      evaluation plan/guidelines, training records and reports generated by five
      tuberculosis units. We assessed the inputs, processes and outputs of the program
      across five tuberculosis units. We calculated the proportion of staff of various
      categories trained and internal quality control (case detection); availability of
      drugs, directly observed treatment short course (DOTS) providers, and supervision
      (case management) and information, education and communication (IEC), and funds
      distribution. (logic model). RESULT: Around 60%-88% of staffs of various
      categories trained with overall 25% gap of supervisory visits. In tuberculosis
      unit (TU) Nurpur, the discordant slides while cross-checking were 8% and 25%. The
      total proportions of sputum positivity are 5.1%; the highest in Kangra, i.e.,
      2.3% (national norms of 10-15%.). There was no full cross-checking of the
      positive slides despite internal quality in place. Increased numbers of the extra
      pulmonary tuberculosis cases (EPTB) are present in all TUs, as high as 61% in TU
      Dharamshala (Normal range 15%-20%). A gap of 20% DOT center exists-the least in
      (58%) in TU Nurpur. The awareness level in the TU Dehra is minimum (51%); more so
      in females and rural set up. CONCLUSION: RNTCP has successfully achieved all its
      targets in all the five TUs of Kangra District as per national norms despite
      several gaps. We recommend (i) filling of vacancies of medics and paramedics with
      reorientation trainings/refresher courses; (ii) conduction of supportive
      supervision by the seniors; (iii) investigation of cause of increased number of
      the extra pulmonary cases, and (iv) need of aggressive IEC activities.

PMID- 21886949
TI  - Effects of upper body resistance training on pulmonary functions in sedentary
      male smokers.
AB  - BACKGROUND: Cigarette smoking is well correlated with lung diseases such as
      chronic obstructive pulmonary disease. It is common among men than women in
      India. In addition, sedentary lifestyle is associated with less efficient
      pulmonary function. Effectiveness of upper body resistance training (UBRT) in
      improving pulmonary function is unclear. Keeping all these factors in view, this
      study aims to examine the effect of UBRT on pulmonary function in male sedentary
      smokers. MATERIALS AND METHODS: This study recruited 36 sedentary male smokers,
      of which 30 were randomized into two groups after fulfilling eligibility criteria
      an exercising experimental group (EG) (N=15) or non-exercising control group (CG)
      (N=15). The EG group were assigned to exercise for 4 weeks, 3 times weekly on non
      consecutive days using UBRT program and breathing exercise. In the CG, only
      breathing exercise was given for 10 min. Both groups were equivalent in baseline
      characteristics. RESULTS: The improvement in forced expiratory volume in one
      second (FEV(1)) and FEV(1)/forced vital capacity (FVC) values were seen
      significant in EG after 4 weeks of UBRT: from 3.62+/-0.56 to 3.96+/-0.51
      (P=0.000) and 0.88+/-0.11 to 0.96+/-0.13 (P<0.001), respectively. But FVC did not
      show significant change in the EG (P=0.430). There were no significant changes in
      FEV(1), FVC, and FEV(1)/FVC values in CG after 4 weeks of intervention. On
      intergroup comparison, significant difference was found between CG and EG for
      FEV(1) and FEV(1)/FVC values. CONCLUSION: Four weeks of UBRT program brought
      about significant changes in the pulmonary function in male sedentary smokers.

PMID- 21886950
TI  - An alternative therapy for idiopathic pulmonary fibrosis by doxycycline through
      matrix metalloproteinase inhibition.
AB  - BACKGROUND: Idiopatiic pulmonary fibrosis (IPF) is a disease of dysregulated
      fibrogenesis with abnormal matrix metalloproteinase (MMPs) activity,
      angiogenesis, and profibrotic milieu wherein MMPs inhibition appears to be target
      based therapy. We evaluated the role of doxycycline as a nonspecific inhibitor of
      MMPs in IPF patients. MATERIALS AND METHODS: Patients of IPF diagnosed on the
      basis of ATS-ERS consensus criteria were put on oral doxycycline in an open
      prospective trial. They were followed up for long term with spirometry, 6 min
      walk test (6MWT), St. Georges respiratory questionnaire (SGRQ), forced vital
      capacity (FVC), and repeat bronchoscopy while on doxycycline monotherapy for over
      24 weeks. Both the initial and follow-up broncho alveolar lavage fluids (BALF)
      from IPF patients (n = 6) and control subjects (n = 6) were looked for MMP-9, -3,
      tissue inhibitor of metalloproteinase (TIMP)-1 and vascular endothelial growth
      factor (VEGF) expression. Additionally, doxycycline's action on MMP activities in
      vitro was tested in BALF of IPF patients. RESULTS: Doxycycline intervention
      showed significant improvement in IPF patients in terms of change in 6MWT, SGRQ,
      FVC, and quality of life. The level of MMP-9, -3, TIMP-1 and VEGF in the BALF
      were found significantly higher in the IPF patients compared to the controls
      while doxycycline therapy reduced those parameters nearer to control value.
      Doxycycline also showed a significant dose-dependent reduction in the in vitro
      MMPs activities in BALF. CONCLUSION: Doxycycline shows significant prospect in
      the treatment of IPF through its anti MMPs activities. This is the first report
      on a case series of long-term doxycycline monotherapy in IPF patients.

PMID- 21886951
TI  - Clinical and demographic characteristics of tracheobronchial variations.
AB  - BACKGROUND: There are various anatomic variations in tracheobronchial system
      (tracheal bronchus, ectopic bronchus, and accessory bronchus). We aimed to
      investigate the bronchoscopic findings of the patients with tracheobronchial
      variations (TBVs) during bronchoscopy and to describe their clinical
      characteristics. MATERIALS AND METHODS: A total of 3322 records of bronchoscopic
      examinations in university hospital and 1560 in chest disease hospital total 4882
      were retrospectively analyzed and 198 (134 male, 64 female) patients were
      diagnosed as TBV. RESULTS: Mean age of patients was 48.5 +/- 17.8 (range, 15-78)
      years. Most of the tracheobronchial variations (n = 68, 33.1%) were localized at
      the right upper lobe bronchus. The most common type of TBVs at this region was
      right upper lobe with two segments. Symptoms were found in 21 (10.2%) patients
      with TBVs (7 accessory cardiac bronchus, 5 tracheal bronchus, 5 accessory
      segmental bronchus in left main bronchus and 4 accessory segmental bronchus in
      right main bronchus). Their symptoms cough, hemoptysis and recurrent pneumonia
      with unknown etiologies were thought as related to TBVs. No other potential
      causes leading these symptoms were found in these patients. CONCLUSION: According
      to our best of knowledge our study population is one of the largest series of
      bronchoscopy for investigate of TBVs. Although TBVs were usually reported as
      asymptomatic, nearly 10% of our patients with TBVs had symptoms such as recurrent
      pneumonia, cough and hemoptysis. TBVs should be taken into consideration in
      symptomatic patients before fiber-optic bronchoscopic examination.

PMID- 21886952
TI  - Prevalence of osteoporosis and osteopenia in advanced chronic obstructive
      pulmonary disease patients.
AB  - BACKGROUND: Reduction of bone mineral density (BMD) is a known and established
      phenomenon in chronic obstructive pulmonary disease (COPD). However, there have
      been no data regarding osteoporosis/osteopenia in COPD patients in India. AIM: To
      look for the degree and frequency of osteoporosis/osteopenia in our OPD patients
      being diagnosed as COPD. MATERIALS AND METHODS: Thirty-seven randomly selected
      patients with COPD were assessed for BMD with commercially available ultrasound
      bone densitometer (HOLOGIC SAHARA) in a pulmonary OPD. Some cofactors for reduced
      BMD were also noted. RESULTS: Out of the 37 COPD (all belonging to the GOLD
      III/IV category) patients studied, the BMD was found to be normal in 10 (27%)
      patients, while 27 (73%) patients were found to have osteopenia/osteoporosis [19
      (51.35%) and 8 (21.62%) patients having osteopenia and osteoporosis,
      respectively]. CONCLUSION: Frequency of osteoporosis and osteopenia was found to
      be very high (73%) in our population of advanced COPD. The data suggest a need
      for further in-depth study regarding the issue.

PMID- 21886953
TI  - Effect of age on presentation with diabetes: Comparison of nondiabetic patients
      with new smear-positive pulmonary tuberculosis patients.
AB  - BACKGROUND: Diabetes mellitus (DM) has been reported to modify the presenting
      features of pulmonary tuberculosis (PTB), but data regarding the effect of
      diabetes on the presentation of PTB are highly variable. OBJECTIVE: To determine
      whether DM alters the demographic, clinical, and radiological manifestations of
      tuberculosis and whether the effect of diabetes varies with the age group of PTB
      patients. MATERIALS AND METHODS: This prospective observational study was
      conducted on new smear-positive PTB patients with DM (PTB-DM group) and non
      diabetic PTB patients (PTB group). Patients of both groups were again divided
      into six age groups (15-29, 30-39, 40-49, 50-59, 60-69, and >70 rears) to analyze
      and compare the impact of age on clinicoradiological presentations of PTB.
      RESULTS: Patients in the PTB-DM group were significantly older (53.34 +/- 14.06
      year) in comparison to their nondiabetic counterparts (PTB group) (44.35 +/-
      18.14 year) (P < 0.001). The former group also had a lower male:female ratio,
      although the difference was not statistically significant (1.16:1 vs. 2.05:1, P =
      0.101). Tuberculin positivity was significantly higher in the PTB group, compared
      with patients in the PTB-DM group (P < 0.004). The proportion of patients with
      lower lung field involvement (P = 0.003) and cavitations (P = 0.005) was also
      higher in the former group compared with the latter. CONCLUSION: Diabetic
      patients with tuberculosis were relatively older, had lower tuberculin
      positivity, and higher proportion of lower lung field involvement and cavitation
      in comparison to nondiabetic patients.

PMID- 21886954
TI  - Diabetes, aging, and tuberculosis.

PMID- 21886955
TI  - Tuberculosis chemotherapy in the 21 century: Back to the basics.
AB  - The key to successful elimination of tuberculosis (TB) is treatment of cases with
      optimum chemotherapy. Poor chemotherapy over time has led to drug-resistant
      disease. Drug resistance of Mycobacterium tuberculosis develops by the selective
      growth of resistant mutants. The incidence of drug-resistant cases depends on the
      number of bacilli and the drug-resistant mutants in the lesion. The latter is low
      for individual drugs and even lower for two and three drugs. Therefore, use of
      combination chemotherapy with three or more drugs results in cure. However,
      irregular treatment, inadequate drugs, inadequate drug doses or addition of a
      single drug to a failing regimen allows selective growth of resistant mutants and
      acquired drug-resistant TB. Contacts of these resistant cases develop primary
      drug resistant TB. Thus, drug resistance in tuberculosis is a "man-made problem".
      Anti-TB chemotherapy must be given optimally by (i) ensuring adequate absorption
      of drugs, (ii) timely diagnosis and management of drug toxicities and (iii)
      treatment adherence. New classes of anti-TB drugs are needed; but are unlikely to
      become available soon. It is vital that the 21(st) century physicians understand
      the basic principles of TB chemotherapy to ensure efficient use of available
      drugs to postpone or even reverse epidemics drug-resistant TB.

PMID- 21886956
TI  - Retraction notice.

PMID- 21886957
TI  - Diffuse interstitial lung infiltrates in a smoker with human immunodeficiency
      virus infection.
AB  - Pulmonary Langerhans cell histiocytosis is a rare interstitial lung disease
      characteristically affecting middle-aged smokers. It has unpredictable clinical
      course and may be associated with malignant neoplasms. Opportunistic lung
      infections are frequently considered when patients with Human immunodeficiency
      virus (HIV) infection present with respiratory symptoms and an abnormal chest X
      ray. Though fiberoptic bronchoscopy with bronchoalveolar lavage is diagnostic for
      infectious etiologies, surgical lung biopsies are preferred to diagnose
      noninfectious lung diseases and to help guide appropriate therapy. In the present
      study, we report a case of progressive bilateral lung infiltrates in a smoker
      with HIV infection which presented a diagnostic dilemma in view of coexistent HIV
      infection. Analysis of clinical symptomatology aided by surgical lung biopsy
      helped in diagnosis.

PMID- 21886958
TI  - An unusual case of fatal pulmonary hemorrhage in pregnancy.
AB  - Rickettsial diseases are common in Srilanka. The spotted fever group of
      rickettsiae presents in many ways, including very severe disease causing
      significant morbidity and mortality. A regional variation of the Rickettsia
      conorii subspecies and differences in clinical presentations are reported. This
      case describes disseminated Rickettsia conorii infection in a pregnant woman
      presenting with endocarditis.

PMID- 21886959
TI  - Pulmonary sequestration cyst in a patient of cerebral palsy.
AB  - Pulmonary sequestration cyst is a rare entity in pediatric patients. Most of the
      time, it is diagnosed as an incidental finding. It is associated with other
      congenital anomalies, especially congenital diaphragmatic hernia. We report a
      patient of cerebral palsy presented with vomiting and recurrent chest infections.
      He was diagnosed to have hiatal hernia on computed tomography scan of chest. At
      operation, a pulmonary sequestration cyst along with hiatal hernia, malrotation,
      and meckel's diverticulum was encountered. The sequestration cyst was managed
      through transhiatal approach.

PMID- 21886960
TI  - Bilateral blunt diaphragmatic rupture.
AB  - Blunt diaphragmatic rupture is an uncommon injury and even less common is the
      bilateral form. This entity poses diagnostic and therapeutic challenges to the
      treating team. Despite the advances in diagnostic modalities, it remains a
      difficult diagnosis leading to missed or late presentations with increased risk
      of morbidity and mortality. We report a case of a 12-year-old girl who sustained
      a blunt abdominal trauma and found to have left hemidiaphragmatic rupture for
      which she underwent laparotomy and repair. Postoperatively, persistent elevation
      of the right hemidaiphragm was noticed, and right-side rupture was suspected and
      confirmed by collar sign on repeated computed tomography scan. The second repair
      was done successfully through a right posteriolateral thoracotomy. She improved
      dramatically and was discharged in an optimal state to be followed in the
      surgical outpatient department.

PMID- 21886961
TI  - A suspected case of transfusion-related acute lung injury.
AB  - Transfusion-related acute lung injury (TRALI) is a rare but serious complication
      of blood transfusion. We present a suspected case of TRALI in a 39-year-old
      female patient who underwent total abdominal hysterectomy under uneventful
      general anesthesia. The patient developed acute desaturation due to
      noncardiogenic pulmonary edema while receiving compatible blood transfusion on
      the second postoperative day. As her symptoms were refractory to supportive
      treatment, she was mechanically ventilated for 3 days and successfully extubated
      on the fourth day. By exclusion, a clinical diagnosis of TRALI was made. The
      treatment for TRALI requires discontinuing transfusion and giving respiratory and
      cardiovascular support. Most cases show clinical improvement in first few hours
      and resolve completely within 96 h.

PMID- 21886962
TI  - Desmoplastic malignant mesothelioma of the pericardium: Description of a case and
      review of the literature.
AB  - Desmoplastic mesothelioma (DMM) is a rare and highly lethal subtype of diffuse
      malignant mesothelioma and is often difficult to distinguish from reactive
      pleural fibrosis. The term "desmoplastic" refers to the growth of fibrous or
      connective tissue. We report the clinical, radiological, and pathological
      features of a primary DMM of the pericardium and a short review of the
      literature. A 72-year-old man was admitted presenting shortness of breath, cough,
      and asthenia. Computed tomography scan showed thickenings and effusions both in
      the pleura and in the pericardium. Histopathological diagnosis was performed by
      surgical pericardial biopsy and confirmed by autopsy. The patient had a history
      of asbestos exposure. Primary mesothelioma of the pericardium is a rare tumor
      occurring in the fourth to seventh decades with nonspecific symptoms and a rapid
      clinical course. The diagnosis is difficult and often needing a surgical
      pericardial biopsy. The prognosis is poor although newer antiblastic drugs seem
      to prolong survival times.

PMID- 21886963
TI  - A cavitary lesion in the lung crossing the fissure.

PMID- 21886964
TI  - An unusual presentation of a common disease.

PMID- 21886965
TI  - Evaluation of a simple bedside tool developed to measure different parameters of
      clubbing.

PMID- 21886966
TI  - Cutaneous tuberculosis.

PMID- 21886967
TI  - New therapeutic approach for latent tuberculosis infection.

PMID- 21886968
TI  - Magnitude of malnutrition amongst hospitalized TB patients.

PMID- 21886969
TI  - Gift authorship - A cause for concern.

PMID- 21886970
TI  - Isoniazid and alopecia.

PMID- 21886971
TI  - Indian commentary on the 2009 KDIGO clinical practice guideline for the
      diagnosis, evaluation, and treatment of chronic kidney disease-mineral and bone
      disorders.
AB  - THIS COMMENTARY PRESENTS THE VIEW OF AN EXPERT GROUP OF INDIAN NEPHROLOGISTS ON
      ADAPTATION AND IMPLEMENTATION OF THE KIDNEY DISEASE: Improving Global Outcomes
      (KDIGO) guidelines for evaluation and management of mineral and bone disorder in
      chronic kidney disease (CKD-MBD) for practice in India. Zonal meetings of
      nephrologists drawn from the cross-section were convened to discuss the KDIGO
      guidelines. Recommendations were presented in a central meeting of zonal
      representatives. The finalized recommendations were reviewed by all the
      participants. There was a broad agreement on most of the recommendations made by
      the KDIGO workgroup. Significant departures in the current guidelines from the
      previous Kidney Disease Outcome Quality Initiative (KDOQI) guidelines were also
      noted. The participants agreed that the available evidence did not allow more
      precise recommendations, and the recommended best practice suggestions were often
      based on relatively weak evidence. There is a remarkable lack of data from Indian
      patients. We comment on specific areas and amplify certain concepts where we feel
      that further guidance that goes beyond what is stated in the document might help
      Indian nephrologists in appropriate implementation of the KDIGO guidelines. This
      commentary is intended to help define practically implementable best practices
      based on current disease concepts and available research evidence, thereby
      positively affecting the quality of management of CKD-MBD in India, and
      eventually improving patient outcomes.

PMID- 21886972
TI  - Urinary indices in nephrotic syndrome.

PMID- 21886973
TI  - Effect of aqueous extract of Tribulus terrestris on oxalate-induced oxidative
      stress in rats.
AB  - The present study was aimed at studying the effect of Tribulus terrestris on
      different parameters of oxidative stress and gene expression profiles of
      antioxidant enzymes in renal tissues of male wistar rats after induction of
      hyperoxaluria. The animals were divided into three groups. The animals in group I
      (control) were administered vehicle only. In group II, the animals were treated
      with ethylene glycol (hyperoxaluric agent) and those in group III were
      administered T. terrestris plant extract in addition to ethylene glycol. All
      treatments were continued for a period of seven weeks. Ethylene glycol feeding
      resulted in hyperoxaluria as well as increased excretion of calcium and
      phosphate. Serum creatinine, uric acid and blood urea nitrogen levels were also
      altered in hyperoxaluric animals. Various oxidative stress parameters viz. lipid
      peroxidation and activity of antioxidant enzymes were used to confirm the
      peroxidant state. Reverse transcription-polymerase chain reaction (RT-PCR)
      analysis was used to confirm whether steady-state transcription level of
      different antioxidant enzymes was altered. T. terrestris significantly reduced
      the excretion of oxalate, calcium, and phosphate along with decreased levels of
      blood urea nitrogen, uric acid and creatinine in serum. T. terrestris also
      reduced hyperoxaluria- caused oxidative stress, and restored antioxidant enzyme
      activity and their expression profile in kidney tissue. Histological analysis
      depicted that T. terrestris treatment decreased renal epithelial damage,
      inflammation, and restored normal glomerular morphology.

PMID- 21886974
TI  - The outcome of proliferative lupus nephritis with pulse cyclophosphamide therapy.
AB  - Proliferative lupus nephritis deserves aggressive therapy and cyclophosphamide
      plays a pivotal role. Thirty nine patients with proliferative lupus nephritis
      (Class III-7 patients and Class IV- 32 patients) with a median follow up of 38
      months were considered for this observational study. All the patients received
      induction therapy with intravenous methylprednisolone. Cyclophosphamide was given
      intravenously initially in monthly pulses for six months and later quarterly
      pulses until remission was achieved or until the target dose (200 mg/kg) was
      reached. The treatment with intravenous methylprednisolone was repeated in the
      event of a nephritic flare. Later the corticosteroid was reduced to a minimum
      effective dose and cyclophosphamide was changed to either azathioprine or
      mycophenolate mofetil. At the time of the last follow up, 82.05% of the patients
      were in remission (complete remission 51.28% and partial remission 30.77%). The
      median interval to achieve remission in responders was 15 months. Early diagnosis
      (P=0.04), a higher creatinine clearance at presentation (P=0.02), and concurrent
      use of an ACEI or an ARB (P=007) significantly favored attaining remission. Five
      patients experienced a doubling of serum creatinine and one of them became
      dialysis dependent. Risk of doubling of serum creatinine correlated with a low
      Ccr (P=0.03) at presentation, occurrence of renal flares (P=0.034) and failure to
      achieve remission (P=0.0001). The parameters like serum creatinine, serum C3,
      serum C4, activity and chronicity indices on renal biopsy, hypertension were not
      statistically significant. Therapy with cyclophosphamide, if initiated early,
      helps in inducing remission and hence can retard the progression to CKD.

PMID- 21886975
TI  - Increased excretion of urinary podocytes in lupus nephritis.
AB  - Podocytes are highly specialized epithelial cells that form part of the
      filtration barrier in the kidney, and their loss reflects a malfunction in
      glomerular filtration, which is usually associated with the progression of the
      disease. Glomerulonephritis is a serious complication that develops in about 50%
      of the lupus patients and is characterized by proteinuria arising from direct or
      indirect podocyte injury. To assess the possible role of podocytes in the
      pathogenesis of lupus nephritis (LN). Urinary and glomerular podocytes were
      detected in the kidney biopsies of patients (n = 17) with lupus nephritis, and
      from control biopsies obtained during autopsies. The WT-1 protein was used as a
      podocyte marker. The cumulative excretion of urinary podocytes was detected in
      the urinary sediments of LN patients and normal healthy controls, and the
      specimens were analyzed by immunohistochemistry, immunofluorescence, and enzyme
      linked immunosorbent assay. The apoptotic index was determined by terminal
      deoxynucleotidyl transferase-mediated dUTP nick end labeling. Gross proteinuria
      in lupus patients was determined via 24-hour urine samples, and the results were
      analyzed by Student t test. Biopsy specimens from 17 patients with class-III or
      IV LN had lower levels of glomerular WT-1 expression than the levels found in
      normal kidneys (P < 0.0001). The reduction of glomerular podocytes in patients
      with lupus nephritis correlated with the cumulative excretion of urinary
      podocytes (P < 0.0001) and proteinuria. There was no correlation between the
      urinary podocytes and the apoptotic index in the LN urinary sediments. A decrease
      in glomerular podocytes is associated with their cumulative excretion in urinary
      sediments; therefore, such findings correlate with proteinuria in lupus nephritis
      patients.

PMID- 21886976
TI  - Urinary indices during relapse of childhood nephrotic syndrome.
AB  - Sodium retention is the hallmark of idiopathic nephrotic syndrome (INS). Sodium
      retention could be secondary to activation of renin-angiotensin-aldosterone axis
      or due to an intrinsic activation of Na(+)K(+) ATPase in the cortical collecting
      duct. Urine potassium/urine potassium + urine sodium (UK(+)/UK(+) + UNa(+)) is a
      surrogate marker for aldosterone activity and can be useful in differentiating
      primary sodium retention from secondary sodium retention in children with INS.
      This was a cross-sectional study of children with INS, presenting to our center
      from June 2007 to June 2008. Children were categorized into those with steroid
      responsive and steroid nonresponsive nephrotic syndrome. One hundred and thirty
      four children with nephrotic syndrome were analyzed. The FeNa(+) was
      significantly lower during relapse than in remission but no such difference was
      observed with UK(+)/UK(+) + UNa(+). The values of FeNa(+) and UK(+)/UK(+) +
      UNa(+) across various categories of nephrotic syndrome were similar. Correlating
      FeNa(+) and UK(+)/UK(+) + UNa(+) with cut-off of 0.5 and 60%, respectively, we
      found 50% of steroid responsive children and 36% of steroid nonresponders having
      a corresponding UK(+)/UK(+) + UNa(+) of <60% along with low FeNa(+) of <0.5%,
      favoring primary sodium retention. Urinary indices did not vary with the type of
      steroid response. In early relapse, the urinary indices revealed an overlap of
      both primary and secondary sodium retention in most stable edematous children
      with nephrotic syndrome.

PMID- 21886977
TI  - Anxiety, locus of control, and coping strategies among end-stage renal disease
      patients undergoing maintenance hemodialysis.
AB  - End-stage kidney disease (ESKD) patients on maintenance hemodialysis (MHD) have a
      lot of anxiety. Anxiety and coping are associated with the locus of control; the
      present investigation aimed to study the state and trait anxiety, locus of
      control, and active and passive coping among patients on MHD. Thirty MHD patients
      and 30 controls were administered State-Trait Anxiety Inventory, Rotter's Locus
      of Control Scale, and Coping Responses Inventory. There were significantly higher
      scores on state and trait anxiety, respectively (67.53 +/- 10.89 vs. 59.40 +/-
      6.97, P < 0.01, and 62.97 +/- 8.45 vs. 58.07 +/- 7.06, P < 0.05), and locus of
      control (11.27 +/- 3.55 vs. 9.04 +/- 1.86, P < 0.01) in patients as compared to
      controls. On coping responses, patients and controls differed on positive
      reappraisal (54.33 +/- 4.67 vs. 51.17 +/- 3.12, P < 0.01), seeking guidance and
      support (58.07 +/- 5.51 vs. 53.27 +/- 4.22, P < 0.01), problem solving (51.03 +/-
      4.70 vs. 47.57 +/- 4.73, P < 0.01), cognitive avoidance (60.27 +/- 6.76 vs. 56.80
      +/- 4.08, P < 0.05), acceptance or resignation (61.67 +/- 6.30 vs. 58.83 +/-
      4.23, P < 0.01), emotional discharge (68.07 +/- 6.78 vs. 64.30 +/- 4.50, P <
      0.05), approach coping (205.57 +/- 10.55 vs. 189.70 +/- 11.37, P < 0.01), and
      avoidance coping (255.30 +/- 16.45 vs. 241.10 +/- 10.50, P < 0.01). A higher
      prevalence of anxiety trait could be the cause of anxiety in MHD patients besides
      the medical problems. The locus of control among patients though a mixed one was
      significantly more toward externalism. Thus, there is a need to identify this
      group well in advance and prepared not only medically but also psychologically
      for MHD.

PMID- 21886978
TI  - Deceased donor organ transplantation: A single center experience.
AB  - Renal transplantation (RTx) is the best therapeutic modality for patient
      suffering from end-stage renal disease (ESRD). Deceased donor organ
      transplantation (DDOT) accounts for <4% of RTx in India. We report 4 years single
      centre experience on DDOT vis-a-vis patient/graft survival, graft function in
      terms of serum creatinine (SCr), rejection episodes, and delayed graft function
      in 160 DDOT. Between January 2006 to December 2009, 160 RTx from 89 donors were
      performed, of which 25.2% were expanded criteria donors. Majority of the donors
      were brain dead due to road traffic/cerebrovascular accidents. The commonest
      recipient diseases leading to ESRD were chronic glomerulonephritis (49%),
      diabetes mellitus (10%), and benign nephrosclerosis (10%). Mean recipient/donor
      age was 35.6+/-14.68 and 44.03+/-18.19 years. Mean dialysis duration
      pretransplantation was 15.37+/-2.82 months. Mean cold ischemia time was 5.56+/
      2.04 hours. All recipients received single dose rabbit-anti-thymocyte globulin
      induction and steroids, mycophenolate mofetil/calcinueurin inhibitor for
      maintenance of immunosuppression. Delayed graft function was observed in 30.6%
      patients and 14% had biopsy proven acute rejection. Over mean follow-up of 2.35+/
      1.24 years, patient and graft survival rates were 77.5% and 89.3% with mean SCr
      of 1.40+/-0.36 mg/dl. DDOT has acceptable graft/patient survival over 4 years
      follow-up and should be encouraged in view of organ shortage.

PMID- 21886979
TI  - Prediction of steroid response in nephrotic syndrome by humoral immunity
      assessment.
AB  - The purpose of this study was to estimate the serum levels of IgG, IgM, and IgA
      in nephrotic syndrome (NS) cases, in activity or in remission, and to detect
      their levels in relation to steroid response by evelautingthe relationship
      between IgG/IgM ratio and response to steroids. We investigated 27 cases with NS
      in activity and in remission and 20 healthy children as controls. Group A
      included 16 NS patients (12.3+/-1.4 years) who were steroid-resistant, frequent
      relapsers, or steroid dependent. Group B included 11 steroid-sensitive NS
      patients with a mean age of 11.6+/-2.1 years. Group C included 20 healthy
      children with a mean age of 12.1+/-2.3 years who were the control group. We found
      lower serum IgG level in NS cases compared with the control group; and it was
      lower in activity than in remission. The levels were lower in Group A compared
      with those of Group B. Serum IgG levels in Group A were as follows: in activity,
      2.29+/-1.13 g/L and in remission, 4.3+/-2 g/L. In Group B, they were 6.2+/-1.2
      g/L and 6.5+/-1.15 g/L in activity and in remission, respectively, and 11.8+/-2.5
      g/L in the healthy control group (P<0.05). There was a direct correlation between
      serum albumin and serum IgG. We found no significant difference in serum IgM and
      IgA levels among studied groups whether in activity or in remission. Serum
      IgG/IgM ratio was lower in activity and in remission in the patient groups than
      in the control group as it was 9.3+/-4.7 in healthy subjects. It was 1.8+/-1.5 in
      Group A in activity and 3.2+/-2 in remission, and in Group B 4.8+/-2.39 in
      activity and 4.8+/-2.4 in remission. We conclude that IgM and IgA show no
      significant difference in NS patients. Serum IgG is lower in NS than in the
      control group and is much lower in activity than in remission. It is lower in
      patients with poor steroid response. We propose a predictive value of IgG/IgM
      ratio in activity, that is, the higher the IgG/IgM ratio in activity, the better
      the prognosis.

PMID- 21886980
TI  - Hypokalemic quadriparesis in Sjogren syndrome.
AB  - We report a 58-year-old woman who presented with acute quadriparesis, bulbar
      weakness, atrial fibrillation, ventricular ectopics, and distal renal tubular
      acidosis with severe hypokalemia. She recovered completely on potassium and
      alkali supplementation. The patient also had hypergammaglobulinemia with probable
      primary Sjogren syndrome.

PMID- 21886981
TI  - Prerenal azotemia from excessive sweating in an adult with a cystic fibrosis gene
      mutation.
AB  - We present the case of a 58-year-old male with chronic kidney disease who was
      admitted to the hospital multiple times with extracellular fluid volume depletion
      and prerenal azotemia. Some episodes were associated with gastrointestinal fluid
      losses and others with profuse diaphoresis in the absence of gastrointestinal
      fluid losses. At the age of 57 years, a common cystic fibrosis transmembrane
      conductance regulator protein mutation and a family history of cystic fibrosis
      were documented. We hypothesize that the abnormal cystic fibrosis transmembrane
      conductance regulator resulted in repeated bouts of excessive sweating,
      extracellular fluid volume depletion, and acute renal failure. This case is
      unique because of the prolonged period of time over which multiple documented
      episodes of prerenal acute renal failure occurred and because of the onset of the
      episodes in adulthood.

PMID- 21886982
TI  - Pheochromocytoma of urinary bladder.
AB  - Pheochromocytoma of urinary bladder are rare tumors. They present with
      nonspecific clinical signs and symptoms, so imaging plays an important role in
      diagnosing and localizing the tumor. We present two cases of bladder
      pheochromocytoma, one of them presented with vague abdominal pain and the other
      with hematuria. Biphasic CT in both the cases showed hypervascular intravesical
      mass suggestive of bladder pheochromocytoma. The lesions were confirmed
      biochemically or on postoperative histopathology. A brief review of the imaging
      in bladder pheochromocytoma is also presented.

PMID- 21886983
TI  - Schistosoma hematobium-associated glomerulopathy.
AB  - Schistosomiasis is the second most devastating tropical parasitic disease
      worldwide and is responsible for many urological complications. However,
      glomerular injury is a rare complication mainly described with Schistosoma
      mansoni. We report a case of membranoproliferative glomerulonephritis (MPGN)
      associated with Schistosoma hematobium infection in a young Senegalese boy living
      in a rural area. Clinical presentation was with steroid-resistant with nephrotic
      syndrome. Renal biopsy showed type 1 MPGN with the presence of S. hematobium eggs
      surrounded by a gigantocellular granuloma. Despite therapy with antihelminthic
      and immunosuppressive drugs, evolution was characterized by progression to end
      stage renal disease over 1 year. More efforts should be made on the prevention
      and early detection of schistosomiasis among at-risk populations.

PMID- 21886984
TI  - Brachiocephalic artery thrombosis in adult nephrotic syndrome.
AB  - Thrombotic events are known to occur in nephrotic syndrome, as these patients
      have a hypercoagulable state. Venous thrombosis is well recognized, but arterial
      thrombosis is rare and is mainly noted in pediatric population. In the present
      study, we report a case of thrombosis of right brachiocephalic artery, embolic
      occlusion of right axillary artery, and right middle cerebral artery territory
      infarction due to thromboembolism in an adult patient with nephrotic syndrome
      (Minimal change disease). Patient underwent thromboembolectomy in the right
      axillary artery followed by anticoagulation therapy.

PMID- 21886985
TI  - Successful renal transplantation following treatment of Aspergillus terreus
      peritonitis in a continuous ambulatory peritoneal dialysis patient.
AB  - Peritoneal dialysis (PD) related peritonitis caused by fungi is a potentially
      life-threatening complication. It diminishes prospects of continuing PD. We
      report a patient with Aspergillus terreus peritonitis treated successfully with
      catheter removal and antifungal therapy and subsequently had a live-related renal
      transplantation. There was no recurrence of the infection in 3 years of follow
      up.

PMID- 21886986
TI  - Megacystis, microcolon, intestinal hypoperistalsis syndrome and bilateral streak
      gonads.
AB  - Megacystis, microcolon, intestinal hypoperistalsis is an uncommon condition
      presenting in neonatal age with features of intestinal obstruction and bladder
      evacuation abnormalities. We present here an infant girl with the diagnosis
      consistent with this entity.

PMID- 21886987
TI  - Thrombotic microangiopathy as a complication of recurrent pancreatitis.
AB  - Acute pancreatitis as a cause of thrombotic microangiopathy is very rare. We
      report a case of 40-year-old woman with idiopathic recurrent pancreatitis, who
      presented with acute pancreatitis complicated by thrombotic microangiopathy.
      Although thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS)
      has been reported as causing acute pancreatitis, the induction of TTP/HUS by
      pancreatitis is rare. As far as we are aware this is the first reported case of
      TTP/HUS in association with pancreatitis in India. Our patient had a complete
      recovery of her thrombotic microangiopathy following plasma exchange therapy.

PMID- 21886988
TI  - Do we need luxurious facilities for exchange of knowledge?

PMID- 21886989
TI  - Candida and calcofluor white: Study in precancer and cancer.
AB  - BACKGROUND: The interest in oral candidosis has waxed and waned from the period
      of Hippocrates. The acquired immune deficiency syndrome (AIDS) epidemic has
      certainly bolstered these figures on oral candidosis, with diabetes and oral
      cancer being no exception. A need for rapid detection of Candida is made possible
      by the use of Calcofluor - White (CFW) stain when examined under a fluorescence
      microscope. The present study was aimed at assessing the efficacy of CFW is
      compared to Gram stain and periodic acid Schiff (PAS) in detection of Candida in
      oral precancer and cancer. MATERIALS AND METHODS: The study group consisted of
      patients with precancer (n=45), cancer (n=45), and control group (n=45). Presence
      of Candida was confirmed by culture inoculation along with a germ tube and
      carbohydrate fermentation test. The cytopathological smears were analyzed by
      papanicolaou - CFW and Gram staining, whereas, tissue sections were stained by
      PAS and CFW staining. RESULTS: Candida albicans was the predominant species
      identified. A highly significant association of Candida was seen more often in
      cancer than in precancer. Both in cytology and histopathology Candida detection
      by CFW was higher. In precancer it was 48.88% in smears and 40% in tissue
      sections, whereas, in cancer 60% in smears and 55.55% in histopathology.
      CONCLUSION: Among the various diagnostic tools used in the present study, the use
      of CFW is seen to be a simple, effective, rapid, and reliable method, both in
      cytopathology and histopathology.

PMID- 21886990
TI  - Intraosseous calcifying epithelial odontogenic tumor in a case with multiple
      myeloma.
AB  - Calcifying epithelial odontogenic tumor (CEOT), also known as Pindborg tumor, is
      a rare benign odontogenic tumor of locally aggressive behavior. It is more common
      in the posterior part of the mandible of adults, typically in the fourth to fifth
      decades. Its origin as well as its true malignant potential is not clearly known.
      It usually starts as a painless swelling and is often concurrent with an impacted
      tooth. A case of CEOT in a 55-year-old man with multiple myeloma is presented.
      Clinical, radiological, and pathologic findings are discussed.

PMID- 21886991
TI  - Rhinomaxillary mucormycosis with cerebral extension.
AB  - Mucormycosis is a rare opportunistic infection caused by fungus belonging to the
      order Mucorales. A case of a controlled diabetic male with rhino maxillary
      mucormycosis, with cerebral extension, is described. The patient presented with
      hemifacial swelling, a nasal twang in his voice, fever, ocular signs, gross
      tissue destruction, and was sluggish. Early recognition of mucormycosis is
      necessary to limit the spread of infection, which can lead to high morbidity and
      mortality. Therefore, health practitioners should be familiar with the signs and
      symptoms of the disease.

PMID- 21886992
TI  - Ewing's sarcoma of zygoma.
AB  - Ewing's sarcoma is a malignant, small, round cell neoplasm that normally affects
      the long bones of the limbs or the pelvis. It is a relatively frequent malignant
      bone tumor in children. The occurrence of the primary tumor in the facial region
      is approximately 2%, with most of the cases affecting the mandible. Primary
      zygoma involvement is rare and as per the available literature only three cases
      have been reported.A case of Ewing's sarcoma that originated in the zygoma of a
      15-year-old girl in reported. Bearing in mind its neuroectodermal origin,
      immunohistochemical studies are essential to distinguish Ewing's sarcoma from
      other small round cell tumors.

PMID- 21886993
TI  - Central schwannoma of mandible.
AB  - Intraoral schwannomas are uncommon and intraosseous ones are even rarer. The
      intrabony lesions account for less than 1% of the central neoplasms.According to
      the literature, there have been reports of 44 cases of intrabony neurilemmomas
      that occurred in either of the jaws. In theis case report. we report a case of
      central schwannoma of the mandible in a 23-year-old female, who presented with a
      swelling involving the right body of the mandible. Radiographs revealed a well
      defined, unilocular radiolucency with bicortical expansion. Histopathology and
      immunohistochemistry confirmed the diagnosis of schwannoma arising from right
      inferior alveolar nerve. The lesion was treated by segmental resection and
      reconstructed with autogenous iliac bone graft.

PMID- 21886994
TI  - Intraosseous calcifying cystic odontogenic tumor.
AB  - The calcifying odontogenic cyst was first reported by Gorlin et al. in 1962. It
      had been classified as a neoplasm related to the odontogenic apparatus because of
      its histological complexity and morphological diversity until it was renamed as a
      calcifying cystic odontogenic tumor by the WHO, in 2005. Here we describe a case
      of mandibular calcifying cystic odontogenic tumor in a 75-year-old male, which
      was present since five years, with a history of occurrence after the extraction
      of teeth in the involved region. The lesion was surgically removed and a
      histopathological examination revealed a cystic tumor with predominance of ghost
      cells and some amount of dentinoid tissue.

PMID- 21886995
TI  - Respiratory implantation cyst of the mandible following orthognathic surgery.
AB  - A cyst following implantation of respiratory epithelium during surgical
      procedures has been documented only rarely. A variety of names have been attached
      to this lesion: respiratory mucocele, respiratory implantation cyst, surgical
      ciliated cyst, and surgical (implantation) cyst. In seven prior case reports, the
      interval between the initiating surgical procedure and diagnostic biopsy of the
      resultant well-circumscribed radiolucency and histopathological demonstration of
      distinctive pseudostratified ciliated columnar epithelial lining has varied from
      4 to 40 years. In the case reported here, chin augmentation used "residual
      maxillary bone" as the donor tissue and likely transplanted sinonasal mucosa into
      the mandible during orthognathic surgery, resulting in a painful anterior
      mandibular cyst lined by respiratory epithelium that was ablated 16 years later.

PMID- 21886996
TI  - Necrotizing sialometaplasia of tongue.
AB  - Necrotizing sialometaplasia, is a benign inflammatory lesion primarily involving
      the minor salivary glands of the hard palate. The lesion often presents itself as
      a deep-seated palatal ulcer with clinical and histological features similar to
      those of a malignant neoplasm. Here we report a case of necrotizing
      sialometaplasia in a 40-year-old female, present on the lateral border of the
      tongue, mimicking squamous cell carcinoma, clinically. A correct diagnosis to
      avoid mutilant surgical treatments is essential, considering that it is a self
      limiting disease.

PMID- 21886997
TI  - Metastasis from breast cancer presenting as an epulis in the upper gingiva.
AB  - Oral metastasis of breast cancer is less common than metastasis to other sites
      like the lung and liver. Breast cancer can metastasize to the oral cavity, with
      presentation like a benign oral lesion. We present an interesting case of breast
      cancer involving the gingiva with sparing of the underlying bone.

PMID- 21886998
TI  - Natal teeth: Case report and review of literature.
AB  - The presence of teeth at birth or within a month post-delivery is a rare
      condition. A newborn, a 2 days old female, with two mandibular incisor natal
      teeth was examined. The teeth were mobile and were extracted because of the fear
      of aspiration and refusal to feed. The purpose of this report is to review the
      literature related to natal teeth epidemiology and discuss their possible
      etiology and treatment.

PMID- 21886999
TI  - Erupted compound odontome.
AB  - Odontomas are considered to be hamartomas rather than a true neoplasm. They
      consist chiefly of enamel and dentin, with variable amount of pulp and cementum
      when fully developed. They are generally asymptomatic and are included under the
      benign calcified odontogenic tumors. They are usually discovered on routine
      radiographic examination. Eruption of an odontoma in the oral cavity is rare.
      Peripheral compound odontomas arise extraosseously and have a tendency to
      exfoliate. In this article we are reporting a case of a 15-year-old girl with
      peripheral compound odontoma, with a single rudimentary tooth-like structure in
      the mandibular right second molar region, which is about to be exfoliated. Its
      eruption in the oral cavity and location in the mandibular posterior region is
      associated with aplasia of the mandibular right second molar, making it an
      interesting case for reporting.

PMID- 21887000
TI  - Living legends: dr. Vinay k. Hazarey.

PMID- 21887001
TI  - Journal reviews.

PMID- 21887002
TI  - From the Editor's Desk.

PMID- 21887003
TI  - Regional odontodysplasia: An unusual case report.
AB  - Regional odontodysplasia is an uncommon developmental anomaly affecting a
      localized area of dentition, with distinctive clinical, radiographic, and
      histological findings. This article reviews a case of a 14-year-old female who
      reported with unerupted maxillary anterior teeth. This case was rare in that it
      involved maxillary dentition with unerupted maxillary anterior teeth on the right
      side, but the left central incisor was missing. The molars on the right side were
      showing some amount of abnormality. Radiographically, the affected teeth had a
      'ghostly' appearance, showing a marked reduction in radiodensity. Both enamel and
      dentin appeared to be very thin, the pulp chamber was exceedingly large, and the
      roots were short with wide open apices. All the characteristics were consistent
      with the diagnosis of regional odontodysplasia. The care and treatment of this
      patient required a multidisciplinary approach. The unerupted maxillary anterior
      teeth were surgically removed, following which temporary prosthetic restoration
      was provided to improve esthetics and to restore the function.

PMID- 21887004
TI  - Oral traumatic neuroma with mature ganglion cells: A case report and review of
      the literature.
AB  - Traumatic neuromas are characterized by the presence of pain, burning, or
      paresthesia, associated with a history of trauma, normally surgery, in the same
      site. In the oral cavity, the most commonly affected sites are the lip, tongue,
      and mental nerve area. Pressure on the suspected area usually provokes pain. They
      microscopically consist of a proliferation of nerve fascicles embedded in a
      background of collagen. We present a case of a 42-year-old Latin American female
      patient complaining of a painful solitary nodule erupting on the lingual surface
      of the mandibular body. Histopathological analysis showed a traumatic neuroma
      associated with mature ganglion cells, which is an extremely unusual finding.
      After complete removal of the lesion the symptoms disappeared. To the best of our
      knowledge, this is the first case of a unique lesion with unusual clinical and
      histopathological features reported in the English language literature.

PMID- 21887005
TI  - Amelogenesis imperfecta: Report of a case and review of literature.
AB  - Amelogenesis imperfecta (AI) is a diverse collection of inherited diseases that
      exhibit quantitative or qualitative tooth enamel defects in the absence of
      systemic manifestations. Also known by varied names such as Hereditary enamel
      dysplasia, Hereditary brown enamel, Hereditary brown opalescent teeth, this
      defect is entirely ectodermal, since mesodermal components of the teeth are
      basically normal. The AI trait can be transmitted by either autosomal dominant,
      autosomal recessive, or X-linked modes of inheritance. Genes implicated in
      autosomal forms are genes encoding enamel matrix proteins, namely: enamelin and
      ameloblastin, tuftelin, MMP-20 and kallikrein - 4. This article presents a case
      reported to Dr. D. Y. Patil, Dental College and Hospital, Pune, India, along with
      a review of this often seen clinical entity.

PMID- 21887006
TI  - Multiple congenital epulis in newborn - A rare presentation.
AB  - A newborn infant with multiple congenital oral swellings can be a striking sight
      for both parents and healthcare professionals involved in neonatal care. Neumann
      first described congenital epulis of a newborn in 1871, hence it is also known as
      Neumann's tumor. Congenital epulis occurs at birth and has a predilection for
      females. Congenital epulis clinically appears as a pedunculated protuberant mass.
      In cases with large lesions, mechanical, oral, and nasal obstruction can impair
      fetal deglutition or interfering with feeding and / or respiratory impairment. We
      are reporting a case of a six-day-old, 3.5 kg newborn female, who had reported to
      our institution with multiple congenital oral swellings arising from the maxilla
      and mandible.

PMID- 21887007
TI  - Lipoid proteinosis.
AB  - Lipoid proteinosis is a rare disorder with autosomal recessive inheritance,
      characterized by progressive deposition of hyaline material in the skin, mucous
      membrane, and different organs of the body, resulting in a multitude of clinical
      manifestations. A 62-year-old male presented with hoarseness of voice since
      infancy, eyelid beading, and generalized acneiform scars on the facial skin and
      extremities, and yellowish papules on his tongue and buccal mucose. The patient
      was diagnosed clinically as a case of Lipoid proteinosis, which was confirmed by
      skin and mucosal biopsy. The objective of the present work is to describe this
      rare entity, with approximately 250 cases found in medical literature. This case
      report also illustrates that Lipoid proteinosis may show protean clinical
      features and yet may remain undiagnosed for many years. This report will
      hopefully spawn further studies that will lead to early diagnosis.

PMID- 21887008
TI  - Salivary duct carcinoma of parotid gland.
AB  - A 40-year old male presented with rapidly growing swelling in the right parotid
      region. Based on the fine needle aspiration cytology report of adenocarcinoma not
      otherwise specified, superficial parotidectomy was performed, which showed the
      features of salivary duct carcinoma by histopathological examination. The smears
      were reviewed to identify the potential pitfalls in the cytological diagnosis of
      salivary duct carcinoma.

PMID- 21887009
TI  - Gorlin-Goltz syndrome.
AB  - Gorlin-Goltz syndrome is an autosomal dominant inherited disorder characterized
      by the presence of multiple odontogenic keratocysts along with various cutaneous,
      dental, osseous, ophthalmic, neurological, and sex organ abnormalities. Early
      diagnosis is essential as it may progress to aggressive basal cell carcinomas and
      neoplasias. Gorlin-Goltz syndrome has rarely been reported from India. We report
      here one such patient, diagnosed at a rural hospital.

PMID- 21887010
TI  - Bilateral fusion of permanent mandibular incisors with Talon's cusp: A rare case
      report.
AB  - Whenever nature diverts from the "normal or usual" it gives rise to something
      called "abnormal or unusual," which we call "a Disorder". Fusion of two teeth is
      a common developmental disorder that is seen by a clinician. However, bilateral
      fusion along with Talon's cusp is very rarely seen and reported in literature.
      This article describes a rare case of the bilateral fusion of permanent
      mandibular central and lateral incisors, along with presence of Talon's cusp on
      the left fused teeth.

PMID- 21887011
TI  - Dentinogenic ghost cell tumor.
AB  - Dentinogenic ghost cell tumor (DGCT) is a rare tumorous form of calcifying
      odontogenic cyst and only a small number of cases have been described. It is a
      locally invasive neoplasm that is characterized by ameloblastoma-like epithelial
      islands, ghost cells and dentinoid. The present report describes a case of a 21
      year-old male with a tumor in the posterior region of the mandible, showing
      features of DGCT.

PMID- 21887012
TI  - Basal cell adenoma in a relatively rare site.
AB  - Basal cell adenoma (BCA) of the salivary glands is an uncommon type of
      monomorphic adenoma. Its most frequent location is the parotid gland. It usually
      appears as a firm and mobile slow-growing mass. Histologically, it is seen as
      nests of isomorphic cells and interlaced trabeculae with a prominent basal
      membrane. There is also slack, hyaline stroma with absence of a myxoid or
      chondroid component. We describe a case of BCA of palatal minor salivary glands,
      a rare site for its occurrence. We also briefly review the literature on the
      same.

PMID- 21887013
TI  - AnimalLectinDb: An integrated animal lectin database.
AB  - Lectins, a class of carbohydrate-binding proteins and widely recognized to play a
      range of crucial roles in many cell-cell recognition events triggering several
      important cellular processes encompass different members that are diverse in
      their protein structures, carbohydrate affinities and specificities, their larger
      biological roles and potential applications. To attain an effective use of all
      the diverse data initially an animal lectin database 'AnimalLectinDb' with
      information pertaining to taxonomic, structural, domain architecture, molecular
      sequence, carbohydrate structure and blood group specificity has been developed.
      It is expected to be of high value not only for basic study in lectin biology but
      also for advanced research in pursuing several applications in biotechnology,
      immunology, and clinical practice. AVAILABILITY: The database is available for
      free at http://www.research-bioinformatics.in.

PMID- 21887014
TI  - An ANN-GA model based promoter prediction in Arabidopsis thaliana using tilling
      microarray data.
AB  - Identification of promoter region is an important part of gene annotation.
      Identification of promoters in eukaryotes is important as promoters modulate
      various metabolic functions and cellular stress responses. In this work, a novel
      approach utilizing intensity values of tilling microarray data for a model
      eukaryotic plant Arabidopsis thaliana, was used to specify promoter region from
      non-promoter region. A feed-forward back propagation neural network model
      supported by genetic algorithm was employed to predict the class of data with a
      window size of 41. A dataset comprising of 2992 data vectors representing both
      promoter and non-promoter regions, chosen randomly from probe intensity vectors
      for whole genome of Arabidopsis thaliana generated through tilling microarray
      technique was used. The classifier model shows prediction accuracy of 69.73% and
      65.36% on training and validation sets, respectively. Further, a concept of
      distance based class membership was used to validate reliability of classifier,
      which showed promising results. The study shows the usability of micro-array
      probe intensities to predict the promoter regions in eukaryotic genomes.

PMID- 21887015
TI  - The integrated web service and genome database for agricultural plants with
      biotechnology information.
AB  - The National Agricultural Biotechnology Information Center (NABIC) constructed an
      agricultural biology-based infrastructure and developed a Web based relational
      database for agricultural plants with biotechnology information. The NABIC has
      concentrated on functional genomics of major agricultural plants, building an
      integrated biotechnology database for agro-biotech information that focuses on
      genomics of major agricultural resources. This genome database provides annotated
      genome information from 1,039,823 records mapped to rice, Arabidopsis, and
      Chinese cabbage.

PMID- 21887016
TI  - miRTour: Plant miRNA and target prediction tool.
AB  - MicroRNAs (miRNAs) are important negative regulators of gene expression in plant
      and animals, which are endogenously produced from their own genes. Computational
      comparative approach based on evolutionary conservation of mature miRNAs has
      revealed a number of orthologs of known miRNAs in different plant species. The
      homology-based plant miRNA discovery, followed by target prediction, comprises
      several steps, which have been done so far manually. Here, we present the
      bioinformatics pipeline miRTour which automates all the steps of miRNA similarity
      search, miRNA precursor selection, target prediction and annotation, each of them
      performed with the same set of input sequences. AVAILABILITY: The database is
      available for free at http://bio2server.bioinfo.uni-plovdiv.bg/miRTour/

PMID- 21887017
TI  - What's new in Emergencies, Trauma, and Shock? Pragmatic possibilities of
      predicting post-STEMI complications using TIMI scores and leukocyte counts.

PMID- 21887018
TI  - Experience of using local flaps to cover open lower limb injuries at an Indian
      trauma center.
AB  - BACKGROUND: Optimal care of open, high-velocity, lower limb injury requires
      surgical skills in debridement, skeletal stabilization, and in providing
      appropriate soft tissue cover. Timely coordination between orthopedic and plastic
      surgeons, though ideal, is often difficult. In our center, orthopedic surgeons
      undertake comprehensive treatment of open fractures including soft tissue cover.
      We reviewed the results of the local flaps of lower limb, done by orthopedic
      surgeons. MATERIALS AND METHODS: We retrospectively reviewed the results of the
      lower limb flaps done between January 2005 and December 2006. All flaps done at
      and below the level of knee were included. RESULTS: There were 105 patients with
      120 flaps during this period. Two patients with two flaps were lost to follow-up.
      The average age was 32 years. Sixty-four patients had Type IIIB Gustilo and
      Anderson injuries. Thirty-nine patients had isolated soft tissue injuries. The
      indications for flaps were exposed bone, tendon, and joint in 45, 11, and 12,
      respectively, or a combination in 35 patients. The flaps done were 51 reverse
      sural artery, 35 gastrocnemius, 25 local fasciocutaneous, and seven foot flaps.
      The flap dimensions ranged from 2 * 2 to 30 * 15 cm. Ninety-three flaps (79%)
      healed primarily. Among 25 flaps (21%) with necrosis, 14 flaps required secondary
      split skin graft for healing, while the other nine flaps healed without further
      surgery. CONCLUSION: Appropriate soft tissue cover provided by orthopedic
      surgeons can help in providing independent, composite care of lower limb
      injuries.

PMID- 21887019
TI  - Comparing the results penetrating colon injuries based on intervention by
      surgeons with different levels of experience in West Indies.
AB  - BACKGROUND: Numerous studies have established the safety of primary repair for
      civilian penetrating colonic injuries with little data exploring the experience
      of surgeon performing the procedure. Owing to financial, staff and administrative
      constraints in the developing world, surgeons-in-training sometimes find
      themselves faced with having to perform major surgery for penetrating colonic
      injuries with no experienced surgeon in attendance, but available for advice via
      phone. With this thought, we collected retrospective data to analyse our outcomes
      based on this practice. MATERIALS AND METHODS: Over a 10-year period 62 patients
      with penetrating colonic trauma underwent laparotomies with analysis done on 53
      cases. Severity of injury, grade of operating surgical staff and outcome were
      noted. Outcomes of "inexperienced surgeons" and "experienced surgeons" were
      compared to determine if a difference exists in outcome based on experience or
      grade of surgeon. RESULTS: A total of 53 patients with penetrating colon injures
      underwent primary repair and/or anastomosis with 18 (34%) performed by
      "inexperienced surgeons" and 35 (66%) by "experienced surgeons". There was one
      death unrelated to colon trauma with an inexperienced surgeon and one anastomotic
      leak in a patient operated on by an experienced surgeon. CONCLUSION: This data
      supports previous reports on the safety of primary repair for penetrating colonic
      injuries and raises the point that in cases of lower severity of injury
      inexperienced surgeons have similar results to experienced surgeons with regard
      to primary repair.

PMID- 21887020
TI  - Profiling pediatric patients involved in automobile crashes in Japan.
AB  - INTRODUCTION: There is little data concerning the injuries induced by being run
      over in children. PROBLEM: Characteristics of injuries suffered in children by
      being run over were investigated. MATERIALS AND METHODS: Between January 1998 and
      December 2007, the medical charts were retrospectively reviewed to investigate
      characteristics of the injuries in pediatric patients run over by a car. Patients
      meeting the following criteria were included: (1) age <= 12 years old; (2) the
      patient was struck by an automobile. The subjects were divided into three groups
      by the mechanisms of injury: (1) run over; (2) carried away; (3) contact.
      RESULTS: Twelve patients had been run over, 44 patients were carried away and 44
      patients had been hit by a car (contact). The average age in the run over group
      was the lowest, followed by that in the carried away group and that in the
      contact group was the highest. The children's coma score and injury severity
      score were not significantly different among the three groups; however, the
      average chest abbreviated injury score was the highest in the run over group,
      followed by that in the carried away group and that in the contact group was the
      lowest. The average duration of admission and survival rate among three groups,
      were not significantly different. CONCLUSION: The patients who were injured due
      to being run over by a car, tended to be younger and to have severe chest injury.

PMID- 21887021
TI  - Analyzing fat embolism syndrome in trauma patients at AIIMS Apex Trauma Center,
      New Delhi, India.
AB  - BACKGROUND: Fat embolism syndrome (FES) is a constellation of symptoms and signs
      subsequent to orthopedic trauma. MATERIALS AND METHODS: The clinical profile of
      FES in the trauma population was studied over 2 years and 8 months. RESULTS: The
      incidence of FES among all patients with long bone and pelvic fractures was 0.7%
      (12). The mean injury severity score was 10.37 (SD 1.69) (range 9-14). The
      diagnosis of FES was made by clinical and laboratory criteria. Hypoxia was the
      commonest presentation (92%). The average days of onset of symptoms were 3.5
      (SD1.29) days. Management included ventilator support in 75%, average ventilator
      days being 7.8 (SD 4.08) days. The average ICU stay and hospital stay were 9.1
      days and 29.7 days, respectively. A mortality of 8.3% (1) was observed.
      CONCLUSION: Fat embolism remains a diagnosis of exclusion and is a clinical
      dilemma. Clinically apparent FES is unusual and needs high index of suspicion,
      especially in long bone and pelvic fractures.

PMID- 21887022
TI  - Profiling genitourinary injuries in United Arab Emirates.
AB  - BACKGROUND: The epidemiology of genitourinary (GU) organ injury following general
      trauma is not well-studied especially in the Middle East. PATIENTS AND METHODS:
      All patients with GU injuries from the Trauma Registry of Al-Ain Hospital were
      studied. The registry data was prospectively collected from March 2003 to March
      2006. RESULTS: Out of 2573 patients in the registry, 22 had GU injuries
      (incidence: 0.9%, 2.0 per 100,000 inhabitants per year). Road traffic collision
      was the most frequent mechanism of injury (50% of all cases). 41% of injuries
      were renal. In 73% of patients, GU injuries were associated with other organ
      injuries, the most frequent of which were injuries to the other abdominal and
      pelvic organs (94%). The mean Injury Severity Score, mean total hospital stay,
      the percentage of patients who required intensive care unit (ICU) admission were
      higher in patients with GU injuries compared to non-GU patients (17.1 vs. 5.5 (P
      0.001), 15.4 vs. 9.2 days (P 0.040) and 43% vs. 8%, (P 0.0001), respectively.
      CONCLUSIONS: The incidence of trauma-related GU injuries in the current study
      appears to be comparable to those reported from the West. Patients with GU organ
      injuries tend to have more severe trauma compared to other patients. Road traffic
      collision was the most common mechanism of injury and the kidney was the most
      frequently injured organ.

PMID- 21887023
TI  - Neurological outcomes of neurosurgical operations for multiple trauma elderly
      patients in Hong Kong.
AB  - BACKGROUND: We aimed to investigate neurological outcomes in elderly patients
      with multiple trauma, and to review their clinical outcomes following
      neurosurgical operations. PATIENTS AND METHODS: The study was conducted in a
      regional trauma center in Hong Kong. We collected prospective data on consecutive
      trauma patients from January 2001 to December 2008. Patients with multiple trauma
      (as defined by Injury Severity Score of 15 or more), with both head injury and
      extracranial injury, were included for analysis. RESULTS: Age over 65 years,
      admission Glasgow Coma Scale (GCS), and Injury Severity Score were significantly
      poor prognostic factors in logistic regression analysis. Eleven (32%) of the 34
      patients aged over 65 who underwent neurosurgical operations attained favorable
      neurological outcomes (GCS 4-5) at 6 months. CONCLUSIONS: Age was an important
      prognostic factor in multiple trauma patients requiring neurosurgical operations.
      Future randomized controlled clinical trials should be designed to recruit
      elderly patients (such as age between 65 and 75 years) at clinical equipoise for
      traumatic hematoma (such as subdural hematoma or traumatic intracerebral
      hematoma) evacuation and assess the quality of life, neurological, and cognitive
      outcomes.

PMID- 21887024
TI  - Combining white blood cell count and thrombosis for predicting in-hospital
      outcomes after acute myocardial infraction.
AB  - INTRODUCTION: Admission white blood cell (WBC) count and thrombosis in myocardial
      infarction (TIMI) risk score have been associated with adverse outcomes after
      acute myocardial infarction (AMI). This study investigated the joint effect of
      WBC count and TIMI risk score on predicting in-hospital outcomes in patients with
      AMI. MATERIALS AND METHODS: WBC count and TIMI risk score were measured at the
      time of hospital admission in 70 patients with AMI. Echocardiogram was done on
      prior to discharge by a cardiologist and ejection fraction (EF) was determined
      according to the Simpson formula. Patients were stratified into tertiles (low and
      high) based on WBC count and TIMI risk score. RESULTS: Patients with a high WBC
      count had a 5.0-fold increase in-hospital congestive heart failure and 2.2
      increases in mortality compared with those with a low WBC count. Patients with a
      high TIMI risk score had a 10-fold increase in congestive heart failure
      presentation and mortality compared with those with a low TIMI risk score. When a
      combination of different strata for each variable was analyzed, a stepwise
      increase in mortality was seen. There were a few number of patients with a high
      WBC count and low TIMI risk score or with a low WBC count and high TIMI risk
      score. These patients had an intermediate risk, whereas those with a high WBC
      count and TIMI risk score had the highest risk. CONCLUSION: These findings
      suggested that a simple combination of WBC count and TIMI risk score might
      provide further information for predicting outcomes in patients with AMI.

PMID- 21887025
TI  - Studying patients of severe traumatic brain injury with severe abdominal injury
      in Japan.
AB  - BACKGROUND: Characteristics of extracranial injury in patients with diffuse
      axonal injury (DAI) have not been clarified. MATERIALS AND METHODS: This
      retrospective study reviewed medical records from January 2003 to December 2007.
      Subjects comprised 35 patients meeting the following criteria: 1) head injury
      without mass lesion; 2) Glasgow coma scale (GCS) on arrival <15; and 3) magnetic
      resonance imaging (MRI) examination including T2*-weighted imaging. Subjects were
      divided into two groups: severe traumatic brain injury (TBI) group (patients with
      GCS <=8, n=19) and moderate TBI group (patients with GCS >8, n=16). RESULTS:
      Shock index (heart rate/systolic blood pressure) was significantly higher in the
      severe TBI group than in the moderate TBI group, while base excess on arrival was
      significantly lower in the severe TBI group than in the moderate TBI group. The
      abbreviated injury scale (AIS) for the face, thorax, extremities and external
      structures showed no significant differences between the severe TBI group, but
      AIS for the abdomen and the sum of extracranial AIS was greater in the severe TBI
      group than in the moderate TBI group. Duration of hospitalization was longer and
      outcomes were worse in the severe TBI group than in the moderate TBI group.
      CONCLUSION: Because patients with severe TBI are more likely to have abdominal
      injury than patients with moderate TBI, physicians should be aware of the
      potential for such complications when treating severe TBI.

PMID- 21887026
TI  - Tight blood glucose control in trauma patients: Who really benefits?
AB  - BACKGROUND: This study was designed to evaluate the effect of intensive insulin
      control (IIT) on outcomes for traumatically injured patients as a function of
      injury severity score (ISS) and age. PATIENTS AND METHODS: A retrospective review
      of 2028 adult trauma patients admitted to the surgical intensive care unit (SICU)
      in a Level I trauma center was performed. Data were collected from a 48-month
      period before (Pre-IIT) (goal blood glucose 80-200 mg/dL) and after (Post-IIT)
      (goal blood glucose level 80-110 mg/dL), an IIT protocol was initiated. Patients
      were stratified by age and ISS. The primary endpoint was mortality. RESULTS:
      There were 784 Pre-IIT and 1244 Post-IIT patients admitted. There was no
      significant difference between Pre-IIT vs. Post-IIT for the mechanism of injury
      or ISS. Values for the Pre-IIT group were significantly higher for mortality
      (21.5% vs. 14.7%, P<0.001) and hospital, but not ICU length of stay were
      decreased. A significant improvement in mortality was demonstrated between Pre
      IIT vs. Post-IIT stratified within the age groups of 41-50, 51-60, and 61 but not
      the groups 18-30 and 31-40. Mean glucose levels (mg/dL) decreased significantly
      after the institution of IIT (144.7+/-1.4 vs. 130.9+/-0.9; P<0.001). In addition,
      the occurrence per patient of blood glucose levels <40 mg/dL increased (0.77% vs.
      2.86%; P=0.001) and blood glucose levels greater than 200 mg/dL was similar
      (39.1% vs. 38.8%; P=0.892) in the Pre-IIT and Post-IIT groups, respectively.
      Glycemic variability, reflected by the standard deviation of each patient's mean
      glucose level during ICU stay, as well as mean glucose level were lower in
      survivors than in nonsurvivors. Finally, multivariable logistic regression
      analysis identified both mean glucose level and glycemic variability as
      independent contributors to the risk of mortality. CONCLUSIONS: The
      implementation of IIT has been associated with a decrease in both hospital length
      of stay as well as mortality. Average glucose value and glucose variability are
      independent predictors of survival. Trauma patients with moderate, severe, and
      very severe injuries benefit most from IIT. These observational data suggest that
      patients over 40 years of age benefited a great deal more than their younger
      counterparts from IIT. This study supports the need for a randomized controlled
      trial to investigate the role of IIT in traumatically injured patients.

PMID- 21887027
TI  - Correlates of new onset peripheral nerve injury in comatose psychotropic drug
      overdose patients.
AB  - AIMS: To investigate the relationship between the duration of comatose state,
      severity of rhabdomyolysis and frequency of peripheral nerve injury (PNI) in
      patients following psychotropic drug overdose. MATERIALS AND METHODS: Medical
      charts were retrospectively reviewed for 41 patients admitted for disturbance of
      consciousness induced by an overdose of psychotropic drugs with rhabdomyolysis
      between October 2004 and February 2010. Subjects were divided into PNI group
      (n=9) and non-PNI control group (n=32). RESULTS: Mean interval between drug
      ingestion and arrival, frequency of pressure ulcers, CK level at the time of
      patient's arrival and maximum CK level during hospitalization, duration of
      hospitalization and morbidity rate were all significantly higher in the PNI group
      than in the control group. CONCLUSION: In patients with a psychotropic drug
      overdose leading to a comatose state, the longer the comatose state, the more
      likely that pressure ulcers and PNI will occur.

PMID- 21887028
TI  - Characteristic of victims of family violence seeking care at health centers in
      Maputo, Mozambique.
AB  - BACKGROUND: Family violence (FV) is a common, yet often invisible, cause of
      violence. To date, most literature on risk factors for family, interpersonal and
      sexual violence is from high-income countries and might not apply to Mozambique.
      AIMS: To determine the individual risk factors for FV in a cohort of patients
      seeking care for injuries at three health centers in Maputo, Mozambique. SETTING
      AND DESIGN: A prospective multi-center study of patients presenting to the
      emergency department for injuries from violence inflicted by a direct family
      member in Maputo, Mozambique, was carried out. MATERIALS AND METHODS: Patients
      who agreed to participate and signed the informed consent were verbally
      administered a pilot-tested blank-item questionnaire to ascertain demographic
      information, perpetrator of the violence, historical information regarding prior
      abuse, and information on who accompanied the victim and where they received
      their initial evaluation. De-identified data were entered into SPSS 13.0 (SPSS,
      version 13.0) and analyzed for frequencies. RESULTS: During the 8-week study
      period, 1206 assault victims presented for care, of whom 216 disclosed the
      relationship of the assailant, including 92 being victims of FV (42.6%). The
      majority of FV victims were women (63.0%) of age group 15-34 years (76.1%) and
      were less educated (84%) compared to national averages. Of the patients who
      reported assault on a single occasion, most were single (58.8%), while patients
      with multiple assaults were mostly married (63.2%). Most commonly, the spouse was
      the aggressor (50%) and a relative accompanied the victim seeking care (54.3%).
      Women most commonly sought police intervention prior to care (63.2%) in
      comparison to men (35.3%). CONCLUSION: In Mozambique, FV affects all ages, sexes
      and cultures, but victims seeking care for FV were more commonly women who were
      less educated and poorer.

PMID- 21887029
TI  - Indicators of potential for rupture for ectopics seen in the emergency
      department.
AB  - BACKGROUND: Emergency departments (ED) frequently evaluate patients with probable
      ectopic pregnancies who go home and may rupture. It would be beneficial to know
      which patient factors are associated with rupture and which are not. OBJECTIVES:
      The purpose of this study was to determine which ED patients with ectopic
      pregnancies are at risk for rupture. MATERIALS AND METHODS: This study was a
      retrospective chart review of all women aged >=18 years during a 5-year period
      who were diagnosed with ectopic pregnancy to a level I ED. Data collected
      included basic demographic information, medical, surgical, obstetric and
      gynecologic history, social and sexual history, findings on physical examination,
      and laboratory values such as urine pregnancy test, beta-hCG, and complete blood
      count. RESULTS: There was a significant difference using a multivariate
      regression analysis with 95% CI in history findings of abdominal pain, nausea,
      vomiting, and urinary tract symptoms. There was a significant difference in
      physical examination of pulse, diastolic pressure, abdominal tenderness,
      peritoneal signs, cervical motion tenderness, and adnexal tenderness. There was
      also a significant difference in beta-hCG, hemoglobin and hematocrit results and
      ultrasound findings of free peritoneal fluid, intrauterine pregnancy and cardiac
      findings between those who ruptured and those who did not. None of these tests
      was able to differentiate those that would go on to rupture. CONCLUSION: The
      result of the study did not find any single sign, symptom, or test that could
      reliably differentiate patients who have a ruptured ectopic from those who do
      not. However, beta-hCG over 1500 mIU was the best variable in explaining the
      variation between those who would or would not go on to rupture after their ED
      visit.

PMID- 21887031
TI  - A 31-year-old female with fever and back pain.
AB  - Primary pyomyositis is a suppurative infection of striated muscle, the diagnosis
      of which is overlooked or delayed due to its rarity and vague clinical
      presentation. Though rare in the United States and temperate zones, pyomyositis
      is more frequently reported from tropical countries. The exact pathogenesis of
      pyomyositis is uncertain in most cases. The disease progresses through three
      stages with characteristic features and require a high index of suspicion to
      institute stage-wise treatment. Newer imaging methods, particularly magnetic
      resonance imaging, have facilitated the accurate diagnosis of the infection and
      of the extent of involvement. Early recognition with appropriate antibiotics in
      the pre-suppurative stage and prompt surgical intervention in the late stages
      form the corner stone of treatment. Delay in diagnosis can result in increased
      morbidity and mortality, especially in diabetics and immunocompromised state.
      Here, we report a case of primary paraspinal pyomyositis in a middle-aged female
      and emphasize the importance of early diagnosis and treatment.

PMID- 21887030
TI  - Managing aluminum phosphide poisonings.
AB  - Aluminum phosphide (AlP) is a cheap, effective and commonly used pesticide.
      However, unfortunately, it is now one of the most common causes of poisoning
      among agricultural pesticides. It liberates lethal phosphine gas when it comes in
      contact either with atmospheric moisture or with hydrochloric acid in the
      stomach. The mechanism of toxicity includes cellular hypoxia due to the effect on
      mitochondria, inhibition of cytochrome C oxidase and formation of highly reactive
      hydroxyl radicals. The signs and symptoms are nonspecific and instantaneous. The
      toxicity of AlP particularly affects the cardiac and vascular tissues, which
      manifest as profound and refractory hypotension, congestive heart failure and
      electrocardiographic abnormalities. The diagnosis of AlP usually depends on
      clinical suspicion or history, but can be made easily by the simple silver
      nitrate test on gastric content or on breath. Due to no known specific antidote,
      management remains primarily supportive care. Early arrival, resuscitation,
      diagnosis, decrease the exposure of poison (by gastric lavage with KMnO(4),
      coconut oil), intensive monitoring and supportive therapy may result in good
      outcome. Prompt and adequate cardiovascular support is important and core in the
      management to attain adequate tissue perfusion, oxygenation and physiologic
      metabolic milieu compatible with life until the tissue poison levels are reduced
      and spontaneous circulation is restored. In most of the studies, poor prognostic
      factors were presence of acidosis and shock. The overall outcome improved in the
      last decade due to better and advanced intensive care management.

PMID- 21887032
TI  - Caring for cerebral venous sinus thrombosis in children.
AB  - Cerebral venous sinus thrombosis in children is increasingly recognized as
      diagnostic tools and clinical awareness has improved. It is a multifactorial
      disease where prothrombotic risk factors and predisposing clinical conditions
      usually in combination constitute the underlying etiology. Clinical features
      range from headache, seizures to comatose state. Although symptomatic treatment
      involving control of infections, seizures and intracranial hypertension is
      uniform, use of anticoagulation and local thrombolytic therapy is still
      controversial. Morbidity and mortality can be significant and long-term
      neurological sequelae include developmental delay, sensorimotor and visual
      deficits and epilepsy.

PMID- 21887033
TI  - Management of penetrating brain injury.
AB  - Penetrating brain injury (PBI), though less prevalent than closed head trauma,
      carries a worse prognosis. The publication of Guidelines for the Management of
      Penetrating Brain Injury in 2001, attempted to standardize the management of PBI.
      This paper provides a precise and updated account of the medical and surgical
      management of these unique injuries which still present a significant challenge
      to practicing neurosurgeons worldwide. The management algorithms presented in
      this document are based on Guidelines for the Management of Penetrating Brain
      Injury and the recommendations are from literature published after 2001. Optimum
      management of PBI requires adequate comprehension of mechanism and
      pathophysiology of injury. Based on current evidence, we recommend computed
      tomography scanning as the neuroradiologic modality of choice for PBI patients.
      Cerebral angiography is recommended in patients with PBI, where there is a high
      suspicion of vascular injury. It is still debatable whether craniectomy or
      craniotomy is the best approach in PBI patients. The recent trend is toward a
      less aggressive debridement of deep-seated bone and missile fragments and a more
      aggressive antibiotic prophylaxis in an effort to improve outcomes. Cerebrospinal
      fluid (CSF) leaks are common in PBI patients and surgical correction is
      recommended for those which do not close spontaneously or are refractory to CSF
      diversion through a ventricular or lumbar drain. The risk of post-traumatic
      epilepsy after PBI is high, and therefore, the use of prophylactic
      anticonvulsants is recommended. Advanced age, suicide attempts, associated
      coagulopathy, Glasgow coma scale score of 3 with bilaterally fixed and dilated
      pupils, and high initial intracranial pressure have been correlated with worse
      outcomes in PBI patients.

PMID- 21887035
TI  - Infantile trauma due to a rat bite.
AB  - We present two cases of extreme neglect with injuries. These are perfect examples
      of gender bias. Our first case is a 20-day-old female neonate was brought to the
      pediatric emergency department with multiple rat bites to the face. A 9-month-old
      female infant was brought to the emergency care division with multiple rat bites
      on the eyes and upper extremities. These cases point towards the existing gender
      bias and extreme social neglect of females in the Indian society.

PMID- 21887034
TI  - Pediatric head trauma.
AB  - Head injury in children accounts for a large number of emergency department
      visits and hospital admissions. Falls are the most common type of injury,
      followed by motor-vehicle-related accidents. In the present study, we discuss the
      evaluation, neuroimaging and management of children with head trauma.
      Furthermore, we present the specific characteristics of each type of pediatric
      head injury.

PMID- 21887036
TI  - Bitemporal compression injury to the head.
AB  - Most cranio-cerebral injuries seen in the emergency department are caused by
      acceleration-deceleration or a direct impact mechanism. Compression or crush
      injury to the head is less commonly seen. A crush injury occurs when a body part
      is subjected a degree of force or pressure, usually after being trapped between
      two heavy objects or hard surfaces. We describe here a case of accidental
      bitemporal and facial compression injury in a young lady.

PMID- 21887037
TI  - Nasal leech infestation causing persistent epistaxis.
AB  - Foreign bodies in the nasal cavity are commonly encountered as a cause of
      epistaxis; however, nasal leech infestation as a cause of unilateral persistent
      epistaxis is very rare. Examination of nasal cavity revealed fleshy material in
      the left nostril, which was identified as leech. The leech was removed with the
      help of an artery forceps following irrigation of the left nostril with normal
      saline and adopting wait-and-watch policy. In developing countries, leech
      infestation as a cause of epistaxis should be suspected in patients with lower
      socioeconomic status or in those living in rural areas who give history of
      drinking polluted water from, or bathing in, stagnant ponds and puddles.

PMID- 21887039
TI  - A rare complication of laparoscopic surgery.
AB  - Gallstone disease is one of the most common problems affecting the digestive
      tract. Symptomatic patients are advised to undergo laparoscopic cholecystectomy
      (LC), which is considered the gold standard of care in these patients. LC has
      clear advantages over traditional surgery such as a shorter hospital stay, an
      earlier return to work and better patient satisfaction. Despite LC being a common
      surgical procedure, it is not totally free from complications. These include
      cardiorespiratory problems, biliary leakage, peritonitis, hemorrhage and superior
      mesenteric artery (SMA) occlusion. We report an unusual and fatal complication of
      LC, being SMA thrombosis complicated by multiple intra-abdominal collections,
      abdominal compartment syndrome, multiorgan failure and septic shock.

PMID- 21887038
TI  - Management of paroxysmal hypertension due to incidental pheochromocytoma in
      pregnancy.
AB  - A 25-year-old, full-term pregnant woman diagnosed with pre-eclampsia was referred
      to our tertiary care hospital with severe resistant hypertension. Her blood
      pressure remained labile despite the usual medications, which led to the
      suspicion of an underlying endocrinological problem. Further biochemical and
      radiological investigations confirmed the diagnosis of pheochromocytoma. The
      patient was invasively monitored and treated with alpha blockade, beta blocker,
      and vasodilators. The primary goals for the management of pheochromocytoma in
      pregnancy are early diagnosis, avoidance of a hypertensive crisis during
      delivery, and definitive surgical treatment. This case illustrates that one needs
      to be cautious when such a presentation of paroxysmal hypertension is present.
      With a multidisciplinary team approach, proper planning, and adequate
      preoperative medical management, pheochromocytoma in pregnancy can be managed
      successfully.

PMID- 21887040
TI  - Severe hypothermia in a patient with spinal cord injury without radiological
      abnormality.
AB  - We report a case of a 64-year-old caucasian male who was transported to the
      emergency department (ED) after being found unconscious on the side of the road.
      On arrival to the ED the patient went into ventricular fibrillation and advanced
      cardiac life support was started at that time. Thirty minutes into the
      resuscitation, after multiple rounds of code drugs and defibrillation attempts,
      the patient was found to be severely hypothermic with a rectal temperature of
      24.9 degrees C (76.9 degrees F). Through the use of passive and active re-warming
      measures the patient's temperature increased enough to allow successful
      cardioversion and stabilization. Within minutes of cardiac stabilization the
      patient regained consciousness and was able to follow commands, but was found to
      be paralyzed from the neck down. Subsequent CT scans revealed no acute fractures,
      subluxations or acute spinal cord injury. This case represents the rare finding
      of severe hypothermia secondary to occult spinal cord injury. Case report was
      taken from case at Bayfront Hospital, St. Petersburg, Florida.

PMID- 21887041
TI  - Surviving a delayed trans-diaphragmatic hepatic rupture complicated by an acute
      superior vena cava and thoracic compartment syndromes.
AB  - We describe the first reported survivor of a delayed trans-diaphragmatic hepatic
      rupture complicated by acute superior vena cava (SVCS) and thoracic compartment
      syndromes (TCS). A thirty one year old male was involved in a boating accident.
      The patient was diagnosed with a grade IV liver laceration, which was initially
      managed with both angio-embolization and open surgical repair. Exactly one month
      from admission, the patient presented with an abrupt cardiac arrest, which was
      further complicated by a SVCS and TCS. The SVCS was managed with bilateral
      thoracostomies which revealed a delayed trans-diaphragmatic hepatic rupture into
      the right chest cavity. The TCS was managed with a decompressive thoraco
      abdominal incision. The patient survived and is now leading a normal life. Our
      success was largely due to an integrated trauma system of physicians, nurses and
      technicians that prompted the early recognition of two potentially life
      threatening complications of a delayed trans-diaphragmatic hepatic rupture.

PMID- 21887042
TI  - Utilization of alteplase in trauma victim with an open abdomen.
AB  - Trauma victims with multisystem injuries are at risk for the development of deep
      vein thrombosis and pulmonary embolus (PE). The use of thrombolytic therapy
      remains very controversial and not well-documented in both the postsurgical and
      trauma subset of patients. Major trauma, surgery or head injury have been noted
      as absolute contraindications to thrombolysis in acute myocardial infarction. The
      decision to utilize thrombolytic therapy cannot be algorithmic; it must be based
      on the assessment findings for each individual patient. The risk to benefit ratio
      should be the major consideration to ensure the best possible outcome is granted.
      Treating injured patients experiencing high-risk PE causing an immediate threat
      to life may necessitate forming a comparative view of the adverse events
      associated with thrombolytic medications.

PMID- 21887043
TI  - Adult necrotizing enterocolitis and non occlusive mesenteric ischemia.
AB  - Adult necrotizing enterocolitis and non occlusive mesenteric ischemia are rare
      causes of acute abdomen in adults. Accurate preoperative diagnosis is often
      difficult in these cases. Here, four cases of massive bowel necrosis with varying
      segments of small and large bowel involvement are described, all of whom
      underwent surgery. These cases give an opportunity to review the literature on
      such lethal diseases including non occlusive intestinal necrosis, neonatal
      necrotizing enterocolitis and adult necrotizing enterocolitis. The similarities
      and differences in etiology, pathophysiology, clinical and radiological findings
      are discussed.

PMID- 21887044
TI  - Organophosphate acetylcholine esterase inhibitor poisoning from a home-made
      shampoo.
AB  - Organophosphate acetylcholine esterase inhibitor poisoning is a major health
      problem in children. We report an unusual cause of organophosphate acetylcholine
      esterase inhibitor poisoning. Two children were admitted to the pediatric
      intensive care unit due to organophosphate acetylcholine esterase inhibitor
      poisoning after exposure from a home-made shampoo that was used for the treatment
      of head lice. Owing to no obvious source of poisoning, the diagnosis of
      organophosphate acetylcholine esterase inhibitor poisoning in one of these
      patients was delayed. Both patients had an uneventful recovery. Organophosphate
      acetylcholine esterase inhibitor poisoning from home-made shampoo is possible. In
      cases where the mode of poisoning is unclear, direct questioning about the use of
      home-made shampoo is warranted, in these cases the skin and particularly the
      scalp should be rinsed thoroughly as soon as possible.

PMID- 21887045
TI  - DORMEX-hydrogen cyanamide poisoning.
AB  - Case reports of acute and chronic exposure to hydrogen cyanamide (DORMEX((r)))
      have been reported but mainly as a result of occupational or accidental exposure
      and without any mortality. We report a case of acute hydrogen cyanamide poisoning
      in a young male due to suicidal intent. The patient was managed under intensive
      care with all the standard protocols for detoxification. However, in spite of
      aggressive management, patient could not be rescued. An extensive literature
      search did not yield any similar case reports. Hence, we report this case to the
      medical community to be aware of the entity.

PMID- 21887046
TI  - Double-lumen endobronchial tube and alternatives in massive hemoptysis: How do
      you want to save lives?

PMID- 21887047
TI  - Atraumatic spontaneous rupture of the non-gravid uterus.

PMID- 21887049
TI  - State of the Globe: The Immunological Quest for an HIV/AIDS Vaccine Continues.

PMID- 21887048
TI  - The falciform ligament sign of pneumoperitoneum.

PMID- 21887050
TI  - Extended-spectrum Beta-lactamase Orthopedic Wound Infections in Nigeria.
AB  - BACKGROUND: Extended-spectrum beta-lactamase (ESBL)-producing Gram-negative
      bacteria are emerging and impacting significantly on the management of patients
      and hospital costs. Besides, they are not being routinely sought after in
      diagnostic laboratories thus contributing to treatment failure. MATERIALS AND
      METHODS: Bacterial isolates from wounds of 45 patients were identified using
      commercial identification kits and antibiotic susceptibility was evaluated by the
      Bauer-Kirby method. Screening and phenotypic confirmation of ESBL production were
      done as prescribed by the Clinical and Laboratory Standards Institute. The
      conjugation experiment was performed by the mating assay in broth between the
      ESBL producers and E. coli ATCC 25922 as the recipient. RESULTS: Out of 102 Gram
      negative bacteria isolated, 36 were positive for ESBL mainly of the
      Enterobacteriaceae family (33) and the rest were oxidase-positive bacilli (3).
      The predominant bacteria were Klebsiella spp. and E. coli. Others were Serratia
      rubidae, Citrobacter freundii, Morganella morgannii, Proteus spp., Providencia
      stuartii, and Enterobacter spp. There was a significant association between
      treatment with third-generation cephalosporins (3GCs) and isolation of ESBLs
      (P=0.0020). The ESBL producers were multiply resistant and moderately sensitive
      to colistin. The conjugation experiment showed that the ESBL gene was transferred
      horizontally and tetracycline, cotrimoxazole, nitrofurantoin, gentamicin, and
      aztreonam resistance genes were co-transferred. No mortality was recorded but the
      mean length of stay in the hospital was 82 days. CONCLUSION: The development and
      spread of ESBL among Gram-negative bacteria and possible horizontal transfer
      calls for concern, especially in view of treatment failure, high treatment cost,
      and consequent discomfort to patients.

PMID- 21887051
TI  - Acute Chlamydia trachomatis respiratory infection in infants.
AB  - OBJECTIVES: This designed was designed to estimate the prevalence of Chlamydia
      trachomatis infection in infants of up to 6 months of age and to assess clinical
      and laboratory indicators as predictors of Chlamydia etiology. MATERIALS AND
      METHODS: A hospital-based study was conducted in Department of Pediatrics,
      Maharani Laxmi Bai Medical College, Jhansi, Uttar Pradesh, India, where infants
      up to 6 months of age (n=50) with features of lower respiratory tract infection
      of at least 1 week duration and fulfilling the inclusion criteria were assessed
      clinically and underwent laboratory investigations using hemogram, Chest X-ray,
      and IgM ELISA. RESULTS: Out of 50 infants, 12 (24%) were tested positive by IgM
      ELISA test for C. trachomatis infection. In age group of up to 2 months 25%
      positivity was seen whereas it was found to be 31.81% in age group of 2-4 months
      and 15% in age group 4-6 months. With the 'P' value less than 0.05, it was found
      that there may be an association of seropositivity of C. trachomatis with
      duration of cough and absolute eosinophil count. CONCLUSION: Chlamydia
      trachomatis is an important cause of lower respiratory tract infection in infants
      below six months of age. The prolonged duration of cough and increased absolute
      eosinophil count may be good indicator of its etiology.

PMID- 21887052
TI  - Clinical Profile of Chikungunya Patients during the Epidemic of 2007 in Kerala,
      India.
AB  - BACKGROUND: The association of the present Chikungunya pandemic with a mutation
      in the Chik virus is already established in many parts of the world, including
      Kerala. Kerala was one of the worst-affected states of India in the Chikungunya
      epidemic of 2006-2007. It is important to discuss the clinical features of
      patients affected by Chikungunya fever in the context of this change in the
      epidemiology of the disease. AIM: This study tries to analyze the clinical
      picture of the Chikungunya patients in Kerala during the epidemic of 2007.
      SETTING AND DESIGN: A cross-sectional survey was carried out in five of the most
      affected districts in Kerala, India. MATERIALS AND METHODS: A two-stage cluster
      sampling technique was used to collect the information. Ten clusters each were
      selected from all the five districts, and the size of the clusters were 18 houses
      each. A structured interview schedule was used for data collection. Diagnosis
      based on clinical signs and symptoms was the major case-finding strategy. RESULTS
      AND CONCLUSION: Of the 3623 residents in the surveyed households, 1913 (52.8%)
      had Chikungunya clinically. Most of the affected were in the adult age group
      (73.4%). Swelling of the joints was seen in 69.9% of the patients, followed by
      headache (64.1%) and itching (50.3%). The knee joint was the most common joint
      affected (52%). The number of patients with persistence of any of the symptoms
      even after 1 month of illness was 1388 (72.6%). Taking bed rest till the relief
      of joint pain was found to be a protective factor for the persistence of the
      symptoms. Recurrence of symptoms with a period of disease-free interval was
      complained by 669 (35.0%) people. Older age (>40 years), a presentation of high
      grade fever with shivering, involvement of the small joints of the hand, presence
      of rashes or joint swelling during the first week of fever and fever lasting for
      more than 1 week were the significant risk factors for recurrence of symptoms
      predicted by a binary logistic regression model. In conclusion, we found that
      there is substantial acute and chronic morbidity associated with the Chikungunya
      epidemic of 2007.

PMID- 21887053
TI  - Impact of basic lymphedema management and antifilarial treatment on acute
      dermatolymphangioadenitis episodes and filarial antigenaemia.
AB  - BACKGROUND: A major factor in the progression of lymphedema is acute
      dermatolymphangioadenitis (ADLA). AIMS: To study ADLA episodes and antigenaemia
      in patients with different grades of filarial lymphedema at pre- and two years
      post-treatment. SETTING AND DESIGN: A prospectively conducted study from May 2008
      through May 2010. PATIENTS AND METHODS: Forty five patients complaining of limb
      swelling with present or past history of limb redness suggestive of ADLA attacks
      were included. Patients were clinically examined for lymphedema grading,
      detection of potential entry points and diagnosis of microfilaraemia. Wuchereria
      bancrofti antigen titer was estimated by "Trop-Ag W. Bancrofti" ELISA kit. Basic
      lymphedema management and treatment with antifilarial drugs were applied.
      STATISTICAL ANALYSIS: Mann-Whitney test and Chi-square test were used. RESULTS:
      The number of ADLA attacks in the pretreatment period, ranged from one to three
      per year. Mean duration of the attacks was 3.87+/-0.79 days. Entry points were
      detected in 82% of cases. The study revealed statistical significance between
      extension and grade of lymphedema and number of ADLA attacks per year (P=0.018
      and 0.022, respectively). Microfilaraemia was detected in four cases and positive
      filarial antigenaemia were detected in 29 patients (64.4). The number of ADLA
      attacks per year significantly decreased from the pre-treatment period (mean:
      2.05+/-0.560) to be 1.23+/-0.706 after one year and 0.89+/-0.575 after two years
      post treatment. There was a significant decrease in the mean antigen titer one
      year and two years after treatment. CONCLUSION: Basic lymphedema management is
      effective for controlling ADLA attacks in areas where lymphatic filariasis is
      endemic.

PMID- 21887054
TI  - Development of ASSURE Dengue IgA Rapid Test for the Detection of Anti-dengue IgA
      from Dengue Infected Patients.
AB  - BACKGROUND: Rapid and early dengue diagnosis is essential for patient management
      and early disease intervention. MP Diagnostics ASSURE((r)) Dengue IgA Rapid Test
      (Dengue IgA RT) was developed for the rapid detection of anti-dengue IgA in
      patients' biological samples. The performance of Dengue IgA RT was examined using
      multiple categories of well-characterized samples. MATERIALS AND METHODS: Dengue
      IgA RT was designed and developed. Following characterization of samples by
      reference ELISAs, the performance of the kit was evaluated. RESULTS: The overall
      sensitivity and specificity of Dengue IgA RT were 86.70% (n=233) and 86.05%
      (n=681) respectively; in which Dengue IgA RT detected 77.42% primary and 92.86%
      secondary cases; compared to 70.97% and 72.14% by IgM-Cap ELISA and 89.25% and
      20% by Non-Structural Protein 1 (NS1) Ag ELISA respectively. Using 125 paired
      samples, Dengue IgA RT showed 84.80% sensitivity at acute phase and 99.20%
      sensitivity at convalescent phase; with 92% specificity at both phases. Dengue
      IgA RT also demonstrated a consistent performance (sensitivity: 85.53%,
      specificity: 80%) with 76 whole blood samples. In detecting all four serotypes of
      DENV (n=162), the performance of Dengue IgA RT was comparable with in-house IgM
      Cap ELISA. Kinetics of anti-dengue IgA production was elucidated with 42.86%
      detection level as early as one-two days after fever onset, which increased to
      83.33% between five and seven days after fever onset. CONCLUSION: Dengue IgA RT
      demonstrated a good performance and is applicable as one of the dengue early
      diagnostic tools at all levels of health care system.

PMID- 21887055
TI  - Anti-infective Potential of Hot-spring Bacteria.
AB  - AIM AND BACKGROUND: Antibiotic resistance currently spans most of the known
      classes of natural and synthetic antibiotics; limiting our options for treatment
      of infections and demanding discovery of new classes of antibiotics. Much effort
      is being directed towards developing new antibiotics to overcome this problem.
      Success in getting novel chemical entities from microbial sources depends
      essentially on novelty of its habitat. The diversity of geographical location
      decides the type of micro-flora. In the past various terrestrial and aqueous
      microorganisms have provided several novel bioactive secondary metabolites of
      pharmaceutical importance. Hot-springs have not been as extensively exploited as
      other terrestrial resources. However, perseverance with such microbes augment the
      probability of getting novel bioactive compounds. MATERIALS AND METHODS: Hot
      springs soil samples were collected from Hot-springs in Maharashtra.
      Actinomycetes and other eubacteria were isolated from these soil samples by
      selective methods and purified. They were classified based on gram's nature and
      morphology. Six representative morphological strains were screened for their anti
      infective potential by agar well diffusion method as reported by Nathan P. et al
      (1974). The bioactivity of the active microbes was confirmed. RESULTS: Seventy
      three strains of bacteria encompassing eight actinomycetes, and 65 eubacteria
      were isolated and purified. Among the actives eubacteria PPVWK106001 showed broad
      spectrum antibacterial activity encompassing both gram positive and gram negative
      bacterial test models. The extract was active against resistant bacteria such as
      MRSA and VREs. Activity was very specific as there was no activity against fungi
      even at 100 fold concentration. The active principle was extractable in butanol.
      CONCLUSIONS: The study showed that Hot-springs exhibit diverse bacteria and it
      serves as potential reservoirs for bacteria of antimicrobial importance with
      diverse facet of activities. Thus Hot-springs microbes have ability to address
      issue of resistant bugs.

PMID- 21887056
TI  - T-cell Epitopes Identified by BALB/c Mice Immunized with Vaccinia Expressing HIV
      1 Gag lie within immunodominant Regions Recognized by HIV-infected Indian
      Patients.
AB  - BACKGROUND: Human immunodeficiency virus (HIV) antigens from transmitted strains
      of HIV would prove crucial in vaccine designing for prevention of HIV infection.
      Immune response generated by Vaccinia construct expressing the HIV-1 gag gene
      from transmitted Indian HIV-1 subtype C strain (Vgag) in BALB/c mice is reported
      in the present study along with the identification of epitopes responsible for
      induction of the immune response. AIMS: The aim of this study was to determine
      immune response generated by the constructs in a mouse model and to understand
      the epitope specificities of the response. SETTINGS AND DESIGN: This was an
      observational study carried out in BALB/c mice. MATERIALS AND METHODS: The
      immunogenecity of Vgag construct was evaluated in BALB/c mice after multiple
      immunizations. T-cell response was monitored by the interferon-gamma ELISPOT
      assay using HIV-1 C Gag overlapping peptides and anti-P24 antibodies were
      estimated by ELISA. STATISTICAL ANALYSIS USED: Graphpad prism software was used
      for statistical analysis and for plotting graphs. RESULTS: IFN-gamma-secreting T
      cells and antibodies were detected against HIV Gag in mice after immunization.
      Although after repeated immunizations, antibody-mediated immune response
      increased or remained sustained, the magnitude of IFN-gamma-secreting T cell was
      found to be decreased over time. The Gag peptides recognized by mice were mainly
      confined to the P24 region and had a considerable overlap with earlier reported
      immunodominant regions recognized by HIV-infected Indian patients. CONCLUSION:
      Vaccinia construct with a gag gene from transmitted HIV-1 virus was found to be
      immunogenic. The Gag regions identified by mice could have important implications
      in terms of future HIV vaccine designing.

PMID- 21887057
TI  - Minimal Inhibitory Concentration of Ceftazidime and Co-trimoxazole for
      Stenotrophomonas Maltophilia using E-test.
AB  - BACKGROUND: Stenotrophomonas maltophilia, previously named as Pseudomonas or
      Xanthomonas maltophilia, is an important nosocomial pathogen AIM: The purpose of
      the present study was to investigate the prevalence of S. maltophilia in Iranian
      hospitals and its susceptibility to available antimicrobial agents. SETTING AND
      DESIGN: A cross-sectional study in Imam Khomeini Hospital affiliated to Tehran
      University of Medical Sciences. MATERIALS AND METHODS: All blood specimens were
      sent to the laboratory for blood culture and biochemical analysis. One hundred
      samples were positive for S. maltophilia. We used disk diffusion and E-test in
      order to determine minimal inhibitory concentration (MIC) of ceftazidime and co
      trimoxazole as the first line antibiotics for S. maltophilia. The tests were
      performed and interpreted according to the guidelines of Clinical Laboratory
      Standards Institute (CLSI). STATISTICAL ANALYSIS: Chi-square test and Kappa
      measurement of agreement were applied as appropriate. RESULTS: S. maltophilia was
      the most frequent pathogen (895 specimens; 38.9%) isolated from the samples which
      were mostly from emergency ward (780 specimens; 33.9%). Ceftazidime MIC(50) and
      MIC(90) were 2 and 32 MUg/ml, respectively (sensitive <=8 MUg/ml and resistant
      >=32 MUg/ml according to CLSI guideline). MIC(50) and MIC(90) for co-trimoxazole
      were 0.5 and 2 MUg/ml, respectively (sensitive <=2 MUg/ml and resistant >=4
      MUg/ml according to CLSI guideline). CONCLUSION: S. maltophilia is the most
      frequent pathogen in our hospital with a high susceptibility to both ceftazidime
      and co-trimoxazole.

PMID- 21887058
TI  - Evaluation of Aro-Tal-AST Complex Protein as a Marker for Differential Diagnosis
      of Mycobacterium Avium Infection.
AB  - PURPOSE: Conventional diagnostic techniques for detecting Mycobacterium avium
      infection are far from satisfactory. As serodiagnostic tests for M. avium
      infection have been shown to be simple and rapid, the present study was carried
      out to identify and evaluate M. avium secretory protein(s) of diagnostic
      potential. MATERIALS AND METHODS: Initially, by differential immunoblotting, a
      specific protein band of 45-50 kDa was recognized. Anion exchange column
      chromatography was used for purification of proteins. After fractionation, blast
      search was carried out. Further immunoreactivity studies were done with M. avium
      and Mycobacterium tuberculosis infected mice sera. Clinical utilization was
      confirmed by conducting indirect enzyme-linked immunosorbent assay (ELISA) with
      serum samples from mycobacterial infected patients. RESULTS: A complex of three
      proteins (Aro-Tal-AST) of molecular weight ~48 kDa, shown to be Aro A homologue
      (Aro), transaldolase (Tal) and aspartate transaminase (AST) by blast search was
      separated. Immunoreactivity studies of purified complex protein with mice sera
      confirmed it to be specific for M. avium infection. Indirect ELISA with patient
      samples further confirmed it to be M. avium infection specific. CONCLUSION: Aro
      Tal-AST protein is specifically recognized by patients infected with M. avium and
      can be used as a marker for simple and rapid ELISA based tests for differential
      diagnosis of M. avium infection in patients with M. avium complex (MAC).

PMID- 21887059
TI  - Comparing absolute lymphocyte count to total lymphocyte count, as a CD4 T cell
      surrogate, to initiate antiretroviral therapy.
AB  - BACKGROUND: The high cost of CD4 count estimation in resource-limited settings is
      a major obstacle in initiating patients on highly active antiretroviral therapy
      (HAART). Thus, there is a need to evaluate other less expensive surrogate markers
      like total lymphocyte count (TLC) and absolute lymphocyte count (ALC).
      OBJECTIVES: To evaluate the correlation of TLC and ALC to CD4 count. To determine
      a range of TLC and ALC cut-offs for initiating HAART in HIV-infected patients in
      resource-limited settings. MATERIALS AND METHODS: In a prospective observational
      cohort study of 108 ART-naive HIV-positive patients, Spearman correlation between
      ALC and CD4 cell count, and TLC and CD4 cell count were assessed. Sensitivity,
      specificity, positive and negative predictive values of various ALC and TLC cut
      offs were computed for CD4 count <200 cells/cu.mm. RESULTS: Good correlation was
      noted between ALC and CD4 (r=0.5604) and TLC and CD4 (r=0.3497). ALC of 1400
      cells/cu.mm had a sensitivity of 71.08% and specificity of 78.26% for predicting
      CD4 cell counts less than 200 cells/cu.mm. Similarly, TLC of 1200 cells/cu.mm had
      a sensitivity of 63.41% and specificity of 69.57%. CONCLUSION: Either ALC or TLC
      may be helpful in deciding when to initiate antiretroviral therapy in resource
      poor settings, though ALC is better than TLC as a surrogate for CD4 counts.

PMID- 21887060
TI  - HIV, Hepatitis B, and Hepatitis C in Zambia.
AB  - OBJECTIVES: Epidemiologic data of HIV and viral hepatitis coinfection are needed
      in sub-Saharan Africa to guide health policy for hepatitis screening and
      optimized antiretroviral therapy (ART). MATERIALS AND METHODS: We screened 323
      HIV-infected, ART-eligible adults for hepatitis B surface antigen (HBsAg) and
      hepatitis C antibody (HCV Ab) at a tertiary hospital in Lusaka, Zambia. We
      collected basic demographic, medical, and laboratory data to determine predictors
      for coinfection. RESULTS: Of 323 enrolled patients, 32 (9.9%; 95% CI=6.7-13.2%)
      were HBsAg positive, while 4 (1.2%; 95% CI=0.03-2.4%) were HCV Ab positive.
      Patients with hepatitis B coinfection were more likely to be <40 years (84.4% vs.
      61.4%; P=0.01) when compared to those who were not coinfected. Patients with
      active hepatitis B were more likely to have mild to moderately elevated AST/ALT
      (40-199 IU/L, 15.8% vs. 5.4%; P=0.003). Highly elevated liver enzymes (>200 IU/L)
      was uncommon and did not differ between the two groups (3.4% vs. 2.3%; P=0.5). We
      were unable to determine predictors of hepatitis C infection due to the low
      prevalence of disease. CONCLUSIONS: HIV and hepatitis B coinfection was common
      among patients initiating ART at this tertiary care facility. Routine screening
      for hepatitis B should be considered for HIV-infected persons in southern Africa.

PMID- 21887061
TI  - Dermatology and HIV/AIDS in Africa.
AB  - Human immunodeficiency virus and the acquired immunodeficiency syndrome
      (HIV/AIDS) have greatly complicated dermatologic disease and the required care in
      most regions of Africa. Opportunistic infections, ectoparasites, Kaposi sarcoma,
      and skin manifestations of systemic infections are exceedingly common in patients
      with HIV/AIDS. Dermatologists have contributed significantly to our knowledge
      base about HIV/AIDS and have played an important educational role regarding the
      clinical manifestations historically. Because of the increased burden of skin
      disease in Africa due to the HIV/AIDS epidemic we must redouble our efforts to
      provide dermatology education to care providers in Africa. We review the burden
      of skin disease in Africa, how it relates to HIV/AIDS and global infectious
      disease, current educational strategies in Africa to address this need, and
      suggest potential solutions to move these efforts forward.

PMID- 21887062
TI  - Toxoplasmosis: a global threat.
AB  - Toxoplasmosis, a disease described worldwide, which is caused by the protozoan
      Toxoplasma gondii, commonly involves the retina. The disease has a higher impact
      in immunocompromised individuals and in congenital infection because of the
      severity of central nervous system involvement. Although simple prophylactic
      measures could reduce transmission, T. gondii seroprevalence is still high,
      especially in South America. Educational campaigns and the development of new
      drugs to prevent primary infection could potentially reduce the burden of the
      disease.

PMID- 21887063
TI  - An update on crimean congo hemorrhagic Fever.
AB  - Crimean Congo hemorrhagic fever (CCHF) is one of the deadly hemorrhagic fevers
      that are endemic in Africa, Asia, Eastern Europe, and the Middle East. It is a
      tick-borne zoonotic viral disease caused by CCHF virus of genus Nairovirus
      (family Bunyaviridae). CCHF not only forms an important public health threat but
      has a significant effect on the healthcare personnel, especially in resource-poor
      countries. India was always a potentially endemic area until an outbreak hit
      parts of Gujarat, taking four lives including the treating medical team. The
      current review is an attempt to summarize the updated knowledge on the disease
      particularly in modern era, with special emphasis on nosocomial infections. The
      knowledge about the disease may help answer certain questions regarding entry of
      virus in India and future threat to community.

PMID- 21887064
TI  - Acute pulmonary schistosomiasis.
AB  - Acute pulmonary schistosomiasis affects non-immune individuals returning from
      endemic areas. Pathogenesis is not well understood. We report a case of acute
      pulmonary schistosomiasis in which lung biopsy was done 10 weeks after exposure
      and it identified the presence of schistosomal ovum surrounded by granuloma.

PMID- 21887066
TI  - Vibrio vulnificus Diarrhea in a Child with Respiratory Infection.
AB  - Vibrio vulnificus is a rare cause of disease and it is often unrecognized and
      underreported. It is a lactose-fermenting, halophilic vibrio causing severe
      disease in immunocompromised patients, but causing a mild type of gastroenteritis
      in healthy people, usually associated with consumption of seafood. We report here
      a case of diarrhea due to V. vulnificus in a male child who was admitted for
      fever, loose motions and productive cough. There was no history of consumption of
      any seafood; so, the source of infection could not be traced. As V. vulnificus is
      a rare entity, clinicians should have a high index of suspicion for the bacteria,
      when patients present with gastrointestinal illness, fever or shock, with or
      without ingestion of raw seafood. Pediatricians should also be alert as the
      bacterium causes a potentially fatal disease in children.

PMID- 21887065
TI  - Bilateral parotid tuberculosis.
AB  - Tuberculosis of parotid is a rare clinical entity, and cases of bilateral
      tubercular parotitis are even rarer. We present a case of bilateral primary
      parotid tuberculosis in a 49-year-old female. The patient received anti
      tuberculosis treatment for six months, resulting in complete resolution of the
      disease. We also review the theories related to the pathogenesis of tubercular
      parotitis, and propose a novel hypothesis about greater involvement of parotid
      gland as compared to other salivary glands in primary tuberculosis.

PMID- 21887067
TI  - Empyema caused by eikenella corrodens.
AB  - Eikenella corrodens is a fastidious, facultative anerobic, non-motile, gram
      negative bacilli that is part of the normal flora of the mouth and upper
      respiratory tract. It is being increasingly recognized as a human pathogen and
      has been implicated in a variety of human infections, including, periodontitis,
      brain abscess, endocarditis, osteomyelitis, intra-abdominal infections, and
      pleuropulmonary infections. We report, for the first time, from the Himalayan
      Kingdom of Nepal, a case of left-sided empyema due to Eikenella corrodens, in an
      83-year-old man. Eikenella corrodens was isolated as a pure growth from the
      pleural aspirate, proving its pathogenic potential. Surgical drainage and an
      appropriate antimicrobial therapy resulted in a therapeutic response. We have
      discussed the difficulties that can be encountered in isolating Eikenella
      corrodens and in choosing appropriate antibiotics for its treatment.

PMID- 21887068
TI  - Imaging findings of disseminated cysticercosis with unusual involvement of spleen
      and pancreas.
AB  - In this study, we present a case of disseminated cysticercosis involving the
      brain, orbit, myocardium, muscle, subcutaneous tissues, pancreas, and spleen.
      Imaging studies are described with emphasis on pancreatic and splenic involvement
      which is a rare manifestation of a rather common disease and has been
      radiologically demonstrated only once previously. Although the involvement of the
      pancreas by parasites leading to pancreatitis has been described previously, in
      our case there was no clinical or biochemical evidence of pancreatitis due to
      infection by cysticerci.

PMID- 21887069
TI  - A Rare Case of Nosocomial Urinary Tract Infection due to Trichosporon asahii.

PMID- 21887070
TI  - The new delhi metallo-Beta-lactamases: their origins and implication for the
      intensivist.

PMID- 21887071
TI  - "Air - bubble" sign - an uncommon presentation of a common disease.

PMID- 21887072
TI  - Polymicrobial Sepsis in an Immunocompetent Host due to Self Injection of Urine.

PMID- 21887073
TI  - Blindness in iraq: leading causes, target patients, and barriers to treatment.
AB  - PURPOSE: To define the main causes of blindness, demographic characteristics and
      barriers to care of blind patients attending a teaching eye hospital in Iraq.
      MATERIAL AND METHOD: Successive new patients, 6 years of age and older, who
      attended three outpatients clinics at Ibn Al-Haetham Teaching Eye Hospital
      (IAHTEH), Baghdad, Iraq, from September 1 to November 30, 2007, were included in
      this study. Inclusion criterion was fulfillment of the World Health
      Organization's definition of blindness. The cause of blindness was identified and
      subjects were interviewed for collection of data on demographic characteristics
      and barriers to treatment. RESULTS: Of 18612 consecutive patients who attended
      the outpatient clinics, 497 (2.7%) patients were blind. Cataract (76.1%),
      diabetic retinopathy (12.9%), and glaucoma (5%) were the leading causes of
      blindness. The majority of blind patients had low socioeconomic status and poor
      educational level. In cases of cataract, the most important barrier to treatment
      was the waiting list at the hospital (53.7%). A lack of awareness was the most
      important barrier to treatment for patients with diabetic retinopathy (54.7%) and
      glaucoma (56%). CONCLUSIONS: The preliminary data from our study will aid in the
      development of blindness prevention programs in Iraq. Priorities include
      decreasing waiting lists for cataract surgeries at governmental hospitals. Active
      health promotion programs for early detection and treatment of diabetic
      retinopathy and glaucoma are also warranted.

PMID- 21887074
TI  - Knowledge of Primary Prevention of Diabetic Retinopathy among General
      Ophthalmologists, Mid Level Eye Care Personnel and General Physicians in Oman.
AB  - OBJECTIVE: We present the outcomes of knowledge of diabetes and associated ocular
      complications among personnel comprising the eye care team in Oman. MATERIALS AND
      METHODS: A closed ended questionnaire was administered during November 2008 and
      November 2009 to eye care team members in six regions of Oman, where trainings
      were held. All participants of these trainings were included in our study. The
      questionnaire comprised 15 questions that tested the knowledge of the diagnosis
      and treatment of diabetes and its ocular complications. They circled the most
      suitable reply for a list of choices. The replies were compared with the gold
      standard (answers from a medical retina specialist, a diabetologist's and general
      ophthalmologists answers). The participants were divided into two groups;
      acceptable (more than 50% score compared to gold standard) and less than desired
      (less than 50% score compared to gold standard.) We estimated the areas of
      acceptable level of knowledge in different subgroups. RESULTS: All 87 (100%) of
      eye care team members participated. Of the 42 general ophthalmologists, 30
      (71.4%) had an acceptable level of knowledge about primary prevention, ideal
      blood sugar and blood pressure levels and complication of diabetes. The
      acceptable level of knowledge among mid level eye care providers and general
      physicians was found in 15 (54.5%) and 4 (33.3%) respondents respectively.
      CONCLUSION: Less than the desired number of participants of the eye care team had
      an acceptable level of knowledge about primary prevention, ideal blood sugar and
      blood pressure levels and complications of diabetes. The training of eye care
      personnel need to enhance knowledge in the weak areas is identified in this
      study.

PMID- 21887075
TI  - Adopting Western Retinopathy of Prematurity Screening Programs in Eastern
      Countries, are we Screening Properly?
AB  - PURPOSE: To describe retinopathy of prematurity (ROP) among Jordanian preterm
      infants and evaluate the efficacy of applying current Western screening
      guidelines for Jordanian preterms. MATERIALS AND METHODS: In this retrospective,
      descriptive hospital-based study, we collected data on preterm infants who were
      referred by their neonatologist for ROP screening at King Abdullah University
      Hospital between July 2006 and June 2007. Guidelines suggested by the American
      Academy of Pediatrics were followed. Additionally, older preterms considered at
      risk for ROP by the neonatal intensive care unit were screened. Any neonate with
      stage 1 ROP or higher in either eye was considered a positive case of ROP.
      RESULTS: Ninety-one preterms were included in the study. The median birth weight
      was 1390 gm (range,730-1980 gms) and the gestational age ranged from 26 to 35
      weeks with 64.8% of preterms <= 32 weeks. ROP occurred in 28.6% of all patients,
      in 20% of infants with birth weight greater than 1500 gms and in 9.4% of preterms
      with gestational age >= 32 weeks. Six patients (6.6%) required laser treatment,
      two with low birth weight greater than 1250 gm and one was 33 weeks of age.
      Consanguinity was identified in 19.2% of infants with ROP while consanguinity in
      infants who did not develop ROP was 1.9%. This difference was statistically
      significant (P<0.05). CONCLUSION: ROP occurs in premature infants in Jordan with
      gestational age above 32 weeks and birth weight above 1250 gm. Future guidelines
      for screening should incorporate the current study outcomes. A prospective,
      population-based is required to set national guidelines for ROP screening in the
      Jordanian population and similarly for different populations worldwide.
      Consanguinity may play a role in ROP development and further genetic studies may
      aid in elucidating the pathogenesis of ROP.

PMID- 21887076
TI  - Evaluation of modified retinopathy of prematurity screening guidelines using
      birth weight as the sole inclusion criterion.
AB  - PURPOSE: The purpose was to determine if birth weight (BW) alone can be the sole
      criterion for screening infants at risk for retinopathy of prematurity (ROP).
      MATERIALS AND METHODS: In this retrospective, observational case series, 208
      infants were screened for ROP using the American Association for Pediatric
      Ophthalmology and Strabismus (AAPOS) Guidelines (1997). Variables examined
      included gestational age (GA), birth weight (BW), and a composite variable BWGA
      Index [(grams * weeks)/1000], which takes into consideration both the birth
      weight and gestational age of the infant. Infants were divided into two groups:
      Group 1, BW <=1250 g, and Group 2, BW >1250 g. Multivariate analysis was
      performed to detect factors predictive of ROP. Receiver operator characteristic
      (ROC) curves were generated to determine the efficacy of screening using the BW,
      GA, and BWGA Index. Statistical analyses were performed with logistic regression
      with a P-value of 0.05 or less indicating statistical significance. RESULTS:
      Varying stages of ROP were present in 116 of 416 eyes. Of the 105 eyes in Group
      2, only 1 eye developed stage 1 ROP. Only Group 1 eyes developed stage 3 or
      higher ROP. The ROC curve for BW alone gave an area under the curve (AUC) of
      0.797 (standard error [SE] = 0.0329, P < 0.0001); for GA, AUC was 0.801 (SE =
      0.0340, P < 0.0001) and for the BWGA Index, the AUC was 0.808 (SE = 0.0324, P <
      0.0001). Using 1250-g BW as a criterion for ROP screening would have decreased
      the number of screenings by 24%, and did not exclude any ROP higher than stage 1.
      CONCLUSION: Data from our neonatal intensive care unit suggest that birth weight
      <= 1250 g alone is an adequate parameter to identify premature infants at risk
      for ROP.

PMID- 21887077
TI  - Intravitreal bevacizumab as a primary treatment for idiopathic choroidal
      neovascularization.
AB  - PURPOSE: To report long-term outcomes of the use of intravitreal bevacizumab in
      subjects with idiopathic choroidal neovascularization (ICNV). MATERIALS AND
      METHODS: Six consecutive subjects with ICNV were included in this prospective
      study. All subjects received 1.25 mg intravitreal bevacizumab at diagnosis. A
      decrease in best corrected visual acuity (BCVA), presence of increased retinal
      edema or hemorrhage, increased retinal thickness on optical coherence tomography
      (OCT) or increased leakage documented by fluorescein angiography prompted further
      injections of bevacizumab. RESULTS: The study cohort was comprised of 3 males and
      3 females with a mean age of 31.17 years. Mean follow-up was 13.8 months (range,
      8 months to 20 months). Following intravitreal bevacizumab injection, vision
      improved in 3 subjects, remained stable in 3 subjects and no patient lost visual
      acuity. The mean BCVA improved to logMAR 0.20 at final follow-up from baseline at
      0.950 logMAR (P=0.031). The mean central macular thickness and central foveal
      thickness at the last postoperative visits were reduced from pre-treatment levels
      of 374.33 +/- 146.52 and 347.16 +/- 213.97 to 251.20+/-35.36 and 215.33 +/- 43.94
      MUm, respectively. (P = 0.99 and P = 0.16, respectively). Four subjects required
      repeat treatments. The total number of repeat treatments was 4. Two subjects
      required no repeat injections, 3 subjects had 1 retreatment and one subject
      required 2 additional treatments. The injections were well tolerated by all the
      subjects, with no ocular or systemic adverse events. CONCLUSION: Intravitreal
      injection of 1.25 mg bevacizumab in patients with ICNV is effective in improving
      and stabilizing vision. Additional studies, particularly determination of optimal
      protocol for timing of re-injection are required to assess long-term effects.

PMID- 21887078
TI  - Retinal detachment after laser in situ keratomileusis.
AB  - PURPOSE: To report characteristics and outcome of rhegmatogenous retinal
      detachment (RRD) after laser in situ keratomileusis (LASIK) for myopia. MATERIALS
      AND METHODS: A retrospective chart review of patients who presented with RRD
      after myopic LASIK over a 10-year period. RESULTS: Fourteen eyes were identified
      with RRD. Of these, two of 6112 LASIK procedures were from our center. The mean
      age of patients with RRD was 35.43 years. The mean interval of RRD after LASIK
      was 37.71 months (range, 4 months to 10 years). The macula was involved in eight
      eyes and spared in six eyes. Retinal breaks included a macular hole in two eyes,
      and giant tear in two eyes. Multiple breaks (>2 breaks) occurred in 6 cases. Pars
      plana vitrectomy (PPV) was performed in 3 (21.4%) eyes, a scleral buckle (SB) was
      performed in 4 (28.5%) eyes and 7 (50%) eyes underwent combined PPV and SB. Mean
      follow-up was 15.18 months (range, 1 month to 7 years). The retina was
      successfully attached in all cases. The final visual acuity was 20/40 or better
      in 7 (50%) eyes, 20/40 to 20/60 in 4 (28.5%) eyes, and 20/200 or less in 3
      (21.4%) eyes. Poor visual outcome was secondary to proliferative
      vitreoretinopathy, epiretinal membrane, macular scar and amblyopia. CONCLUSION:
      The prevalence of RRD after LASIK was low at our institute. Anatomical and visual
      outcomes were acceptable in eyes that were managed promptly. Although there is no
      cause-effect relationship between LASIK and RRD, a dilated fundus examination is
      highly recommended before and after LASIK for myopia.

PMID- 21887079
TI  - Antibiotic susceptibility patterns of pseudomonas corneal ulcers in contact lens
      wearers.
AB  - PURPOSE: To evaluate the resistance or susceptibility of Pseudomonas aeruginosa,
      the most common pathogen in contact lens keratitis and corneal ulcer, to
      different antibiotic regimens. MATERIALS AND METHODS: This cross-sectional study
      included all patients with recently diagnosed contact lens corneal ulcer whose
      culture results were positive for P. aeruginosa, from March 2009 to March 2010.
      The empirical antibiotic therapy was changed to appropriate antibiotics according
      to the culture results, provided that satisfactory clinical improvement was not
      achieved with the initial antibiotic regimen. The overall sensitivity or
      resistance of P. aeruginosa to the most commonly used antibiotics was assessed
      based on the results of the antibiograms. RESULTS: Fifty-two patients (43 females
      and 9 males) were included. Forty-five patients (86%) were wearing cosmetic
      contact lenses, while 7 patients (14%) were using therapeutic contact lenses.
      Thirty-nine patients (75%) were hospitalized and13 patients (25%) were followed
      up through an outpatient clinic. Thirty patients (58%) had central ulcers,
      whereas 22 patients (42%) had peripheral ulcers. Twelve patients (23%) had
      hypopyon in their first exam. The mean time to diagnose the ulcer after the last
      time wearing was 2 days (range: 12 hours to 5 days). AMT was required for 10
      patients (19%). Based on the antibiograms, PA was shown to be sensitive in 100%
      of cases to ceftazidime and ciprofloxacin. Amikacin, imipenem, and gentamicin
      were the second most effective antibiotics. CONCLUSION: P. aeruginosa was highly
      sensitive to ceftazidime, ciprofloxacin, and amikacin. All cases were resistant
      to cefazolin. Resistance to multiple antibiotics might be a significant concern
      in patients with corneal ulcers. In referral centers dealing with corneal ulcers,
      the initial antibiotic regimens should be changed from time to time to prevent
      this phenomenon.

PMID- 21887080
TI  - Outcomes of Retreatment after Aborted Laser In Situ Keratomileusis due to Flap
      Complications.
AB  - PURPOSE: To determine the refractive outcomes and complications of retreatment
      after aborted primary laser in situ keratomileusis (LASIK) due to flap
      complications. MATERIALS AND METHODS: This retrospective study evaluated 50
      retreated eyes that had flap complications during primary LASIK at the Eye
      Consultants Center in Riyadh, Saudi Arabia. Data were analyzed for patients with
      at least 3 months follow-up post retreatment. RESULTS: Thirty-three eyes of 31
      consecutive patients with 3 months follow-up or later post retreatment were
      included. The primary LASIK was aborted due to incomplete flaps in 22 eyes
      (66.7%), buttonhole flaps in 7 eyes (21.2%), free partial flaps in 3 eyes (9.1%),
      and a free complete flap in 1 eye (3.0%). Twenty-two eyes (66.7%) were retreated
      with LASIK, and 11 eyes (33.3%) were retreated with surface ablation. The mean
      spherical equivalent (SE) was -0.23 +/- 0.72 D, the mean astigmatism was -0.65 +/
      0.89 D, and the mean loss of the best corrected visual acuity (BCVA) was 0.78
      lines at the final postoperative visit. At the last postoperative visit, 20/30 or
      better BCVA was achieved in 90.1% of eyes that underwent retreatment with LASIK
      and in 91% of eyes that were retreated with surface ablation. There was no
      statistical difference in postoperative SE between eyes retreated with LASIK and
      eyes retreated with surface ablation (P = 0.610). There was no statistical
      difference in postoperative BCVA between eyes retreated with LASIK and those
      retreated with surface ablation (P = 0.756). There were no intraoperative
      complications and no eyes required a second retreatment. CONCLUSION: Creation of
      a flap after a previous intraoperative flap complication was not associated with
      any complications. The refractive outcomes of retreatment with LASIK or surface
      ablation were comparable and reasonably favorable.

PMID- 21887082
TI  - Response of diabetic papillopathy to intravitreal bevacizumab.
AB  - Diabetic papillopathy is an uncommon hyperemic optic disc swelling that occurs in
      patients with long-standing diabetes, is typically self-resolving with minimal
      effect on vision, and is likely ischemic in origin. The purpose of the current
      report is to document the response of diabetic papillopathy to intravitreal
      injection of bevacizumab (Avastin, Genentech Inc, San Francisco, California,
      USA), a humanized monoclonal antibody to vascular endothelial growth factor.

PMID- 21887081
TI  - Visual Outcomes of Conductive Keratoplasty to Treat Hyperopia and Astigmatism
      After Laser in situ Keratomileusis and Photorefractive Keratectomy.
AB  - AIM: To determine the effect of conductive keratoplasty (CK) for the treatment of
      induced hyperopia and astigmatism after complicated myopic laser in situ
      keratomileusis (LASIK) or photorefractive keratectomy (PRK). MATERIALS AND
      METHODS: In this interventional case series, 11 eyes of seven subjects with a
      history of previous LASIK or PRK with inadequate stromal bed or flaps
      complications were enrolled. Inclusion criteria included residual spherical
      hyperopia of 1.00 to 3.00 diopters (D) and cylinder of -0.75 to -3.00 D. The
      modified Refractec nomogram and the LightTouch technique of CK were performed on
      all eyes. To treat cylinder, a pair of spots per -0.75 D of cylinder were
      delivered to the flat meridian. Uncorrected visual acuity at near and far (UCVAN
      and UCVAF respectively, logMAR), best corrected VA at near and far (BCVAN and
      BCVAF respectively, logMAR) were measured. Refractive outcome, contrast
      sensitivity, wave front aberrations were measured preoperatively and
      postoperatively. Statistical analysis was performed with the Wilcoxon signed rank
      test and the repeated measures analysis of variance with P<0.05 indicating
      statistically significant change from preoperatively to 1 year postoperatively.
      RESULTS: The mean preoperative sphere (MS) was 2.57 +/- 1.19 D and cylinder (MC)
      was -1.5 +/- 0.49 D. Postoperatively, there was a significant decrease in MS to
      0.36+/-0.98 D (P=0.003) and MC to -1.25 +/- 0.76 D at 1 year (P<0.05, both
      cases). Spherical equivalent (SE) significantly decreased from +2.13 +/- 1.09 D
      to -0.47 +/- 1.29 D (P<0.001). The mean UCVAN significantly improved from 0.56 +/
      0.32 preoperatively to 0.17 +/-0.16 postoperatively (P=0.003). The mean UCVAF
      was 0.29 preoperatively and 0.22 postoperatively (P=0.353). Mean BCVAN was 0.18
      and 0.02 after surgery, and mean BCVAF for far was 0.07 (P>0.05, both cases).
      CONCLUSIONS: CK is a predictable and reliable method to correct hyperopia after
      LASIK and PRK, however cylinder correction may induce irregular and unpredictable
      outcomes and a modified nomogram is required for further studies.

PMID- 21887083
TI  - Temporary Exudative Retinal Detachment following Photodynamic Therapy in a
      Patient with Retinal Capillary Hemangioblastoma.
AB  - A 21-year-old male with von Hippel-Lindau syndrome was treated for a retinal
      hemangioblastoma with photodynamic therapy (PDT). We employed the standard PDT
      protocol with doubled treatment duration. Seven days after the procedure, there
      were some perilesional intra- and subretinal hemorrhages and significant
      exudative retinal detachment extending inferiorly. Four weeks later, the
      hemorrhages had mostly cleared, and diminished subretinal fluid and partial
      regression of the hemangioblastoma were noted. PDT might induce temporary
      subretinal fluid accumulation in eyes with retinal hemangiomas.

PMID- 21887084
TI  - Acute papillitis in young female with toxoplasmosis.
AB  - Papillitis and complicating acute toxoplasma retinochoroiditis, are unusual and
      atypical features of toxoplasmosis. This report presents a female with unusual
      acute papillitis. This patient had an active toxoplasmic chorioretinitis lesion
      that appeared to involve the optic nerve head and a major blood vessel as well as
      central nervous systems (CNS). Papillitis may be secondary to juxtapapillary
      retinitis (Jensen choroiditis). Very rarely, the optic nerve head may be the
      primary site of involvement. This case report illustrates a rare presentation of
      acute papillitis in a young immunocompetent female.

PMID- 21887085
TI  - Radial keratoneuritis as a presenting sign in acanthamoeba keratitis.
AB  - The visual outcomes of Acanthamoeba keratitis, a rare cause of corneal infection,
      can be devastating. This paper reports two contact lens wearers with severe pain
      and photophobia who presented to the emergency room. Biomicroscopy revealed
      radial keratoneuritis in both individuals. Tissue culture on a nonnutrient agar
      plate with Escherichia coli overlay resulted in a heavy growth of Acanthamoeba.
      The inpatient treatment included 0.02% polyhexamethylene biguanide,
      chlorhexidine, neomycin/polymyxin B/bacitracin (Neosporin), and oral fluconazole,
      which successfully controlled the corneal infection and improvement in the best
      corrected visual acuity in both patients. Infection did not recur during the 12
      month follow-up period. Acanthamoeba keratitis can present as radial
      keratoneuritis, mimicking other common corneal infections resulting in diagnostic
      and treatment delays. Early diagnosis and prudent treatment of Acanthamoeba
      keratitis are the keys to restoring vision and avoiding the subsequent need for
      penetrating keratoplasty.

PMID- 21887086
TI  - Superior and inferior ophthalmic veins thrombosis with cavernous sinus
      meningioma.
AB  - Ophthalmic vein thrombosis is an extremely rare entity. We present a case of
      middle-aged female who presented with proptosis. Contrast-enhanced computed
      tomography and magnetic resonance imaging showed cavernous sinus meningioma with
      ipsilateral superior and inferior vein thrombosis. A brief review of the vascular
      involvement of the meningioma and ophthalmic vein thrombosis is presented along
      with the case.

PMID- 21887087
TI  - The association between early conduct problems and early marijuana use in college
      students.
AB  - Early conduct problems have been linked to early marijuana use in adolescence.
      The present study examines this association in a sample of 1,076 college students
      that was divided into three groups: 1) early marijuana users (began marijuana use
      prior to age 15; n=126), 2) late marijuana users (began marijuana use at or after
      age 15; n=607), and 3) non-users (never used marijuana; n=343). A conduct problem
      inventory used in previous studies was adapted for use in the present study.
      Early conduct problems were associated with early marijuana use but not with late
      marijuana use, holding constant other risk factors. Results suggest that early
      conduct problems are a risk factor for early marijuana use even among
      academically-achieving college-bound students.

PMID- 21887090
TI  - Combined use of high-reflective index vitrectomy meniscus contact lens and a
      noncontact wide-angle viewing system in vitreous surgery.
AB  - BACKGROUND: The aim of this study was to assess the combined use of a high
      reflective index vitrectomy (HHV) meniscus contact lens and a noncontact wide
      angle viewing system in vitreous surgery. METHODS: Twenty-three gauge vitrectomy
      was performed with combined use of a HHV meniscus contact lens and a noncontact
      wide-angle viewing system. When delicate manipulation of the retina such as
      internal limiting membrane peeling was performed, only the HHV meniscus lens was
      used. RESULTS: Advantages of this combination procedure include the ability to
      observe the peripheral fundus image, easy access to the posterior pole without
      exchange of the contact lens when needed, keeping the corneal surface wet covered
      by a contact lens, and the good view afforded during fluid-air exchange.
      CONCLUSION: Combined use of a HHV meniscus contact lens and a noncontact wide
      angle viewing system is useful for vitreous surgery. It has the advantages of
      both contact and noncontact wide-angle viewing systems.

PMID- 21887088
TI  - High-resolution wide-field imaging of perfused capillaries without the use of
      contrast agent.
AB  - PURPOSE: Assessment of capillary abnormalities facilitates early diagnosis,
      treatment, and follow-up of common retinal pathologies. Injected contrast agents
      like fluorescein are widely used to image retinal capillaries, but this highly
      effective procedure has a few disadvantages, such as untoward side effects,
      inconvenience of injection, and brevity of the time window for clear
      visualization. The retinal function imager (RFI) is a tool for monitoring retinal
      functions, such as blood velocity and oximetry, based on intrinsic signals. Here
      we describe the clinical use of hemoglobin in red blood cells (RBCs) as an
      intrinsic motion-contrast agent in the generation of detailed noninvasive
      capillary-perfusion maps (nCPMs). PATIENTS AND METHODS: Multiple series of nCPM
      images were acquired from 130 patients with diabetic retinopathy, vein occlusion,
      central serous retinopathy, age-related macular degeneration, or metabolic
      syndrome, as well as from 37 healthy subjects. After registration, pixel value
      distribution parameters were analyzed to locate RBC motion. RESULTS: The RFI
      yielded nCPMs demonstrating microvascular morphology including capillaries in
      exquisite detail. Maps from the same subject were highly reproducible in repeated
      measurements, in as much detail and often better than that revealed by the very
      best fluorescein angiography. In patients, neovascularization and capillary
      nonperfusion areas were clearly observed. Foveal avascular zones (FAZ) were
      sharply delineated and were larger in patients with diabetic retinopathy than in
      controls (FAZ diameter: 641.5 +/- 82.3 versus 463.7 +/- 105 MUm; P < 0.001). Also
      visible were abnormal vascular patterns, such as shunts and vascular loops.
      CONCLUSION: Optical imaging of retinal capillaries in human patients based on
      motion contrast is noninvasive, comfortable, safe, and can be repeated as often
      as required for early diagnosis, treatment guidance, and follow up of retinal
      disease progression.

PMID- 21887091
TI  - Central and peripheral intraocular pressure measured by a rebound tonometer.
AB  - PURPOSE: We investigated at which corneal region the intraocular pressure as
      measured by the Icare((r)) rebound tonometer (Finland Oy, Espoo, Finland)
      (hereinafter referred to as IC) was closest to the intraocular pressure as
      measured by the Goldmann applanation tonometer (hereinafter referred to as GT).
      We also investigated which parameters would be best for preparing the most
      suitable model for predicting GT. METHODS: A total of 102 normal eyes in 102
      subjects were enrolled. IC measurements were carried out at the central,
      superior, inferior, temporal, and nasal regions of the cornea (ICC, ICS, ICI,
      ICT, and ICN, respectively), followed by GT calculations. Differences between GT
      and IC were analyzed using the Bland-Altman method. Stepwise multiple regression
      analysis was performed using GT as the objective variable, and age, laterality of
      eye, spherical equivalent refractive error, corneal radius, axial length, central
      corneal thickness, GT, ICC, ICS, ICI, ICT, and ICN as the explanatory variables.
      RESULTS: IC was higher than GT at all of the corneal regions, but the region with
      the least bias was ICC, followed by ICT. In the multiple regression analysis, the
      following prediction formula was calculated: GT = (0.445 * ICC) + (0.198 * ICN) +
      3.022. When ICC was excluded from the explanatory variables, ICT had the highest
      partial correlation coefficient with GT. CONCLUSION: ICC was closest to GT, but
      GT could be explained better by adding ICN to the prediction model. Moreover, in
      instances where ICC cannot be calculated or where reliability is clearly poor due
      to abnormal ocular rigidity, ICT was the closest to GT measured in the central
      corneal region.

PMID- 21887092
TI  - Aqueous humor penetration of topical bimatoprost 0.01% and bimatoprost 0.03% in
      rabbits: response to authors.

PMID- 21887093
TI  - Comparison of Hanna and Hessburg-Barron trephine and punch systems using
      histological, anterior segment optical coherence tomography, and elliptical curve
      fitting models.
AB  - BACKGROUND: This study analyzes the characteristics of donor and recipient tissue
      preparation between the Hessburg-Barron and Hanna punch and trephine systems by
      using elliptical curve fitting models, light microscopy, and anterior segment
      optical coherence tomography (AS-OCT). METHODS: Eight millimeter Hessburg-Barron
      and Hanna vacuum trephines and punches were used on six cadaver globes and six
      corneal-scleral rims, respectively. Eccentricity data were generated using
      measurements from photographs of the corneal buttons and were used to generate an
      elliptical curve fit to calculate properties of the corneal button. The
      trephination angle and punch angle were measured by digital protractor software
      from light microscopy and AS-OCT images to evaluate the consistency with which
      each device cuts the cornea. RESULTS: The Hanna trephine showed a trend towards
      producing a more circular recipient button than the Barron trephine (ratio of
      major axis to minor axis), ie, 1.059 +/- 0.041 versus 1.110 +/- 0.027 (P = 0.147)
      and the Hanna punch showed a trend towards producing a more circular donor cut
      than the Barron punch, ie, 1.021 +/- 0.022 versus 1.046 +/- 0.039 (P = 0.445).
      The Hanna trephine was demonstrated to have a more consistent trephination angle
      than the Barron trephine when assessing light microscopy images, ie, +/-14.39
      degrees  (95% confidence interval [CI] 111.9-157.7) versus +/-19.38 degrees  (95%
      CI 101.9-150.2, P = 0.492) and OCT images, ie, +/-8.08 degrees  (95% CI 106.2
      123.3) versus +/-11.16 degrees  (95% CI 109.3-132.6, P = 0.306). The angle
      created by the Hanna punch had less variability than the Barron punch from both
      the light microscopy, ie, +/-4.81 degrees  (95% CI 101.6-113.9) versus +/-11.28
      degrees  (95% CI 84.5-120.6, P = 0.295) and AS-OCT imaging, ie, +/-9.96 degrees 
      (95% CI 95.7-116.4) versus +/-14.02 degrees  (95% CI 91.8-123.7, P = 0.825).
      Statistical significance was not achieved. CONCLUSION: The Hanna trephine and
      punch may be more accurate and consistent in cutting corneal buttons than the
      Hessburg-Barron trephine and punch when evaluated using elliptical curve fitting
      models, light microscopy, and AS-OCT.

PMID- 21887095
TI  - Evaluation of intralesional propranolol for periocular capillary hemangioma.
AB  - BACKGROUND: The purpose of this study was to evaluate the use of intralesional
      propranolol injection in the management of periocular capillary hemangioma.
      METHODS: A prospective study was performed in 22 consecutive patients with
      periocular hemangioma. Twelve patients underwent intralesional propranolol
      injection and ten patients underwent intralesional triamcinolone injection. The
      size of the lesion was measured serially every week during the first month, every
      2 weeks for the second month, and then monthly for another 2 months. The
      refractive error and degree of ptosis if present were measured before injection
      and at the end of the study. RESULTS: There was reduction in the size of
      hemangioma, astigmatic error, and degree of ptosis in both groups. The difference
      in outcome between both groups was not statistically significant. Rebound growth
      occurred in 25% of the propranolol group and 30% of the steroid group but
      responded to reinjection. No adverse effects were reported during or after
      intralesional propranolol injection. CONCLUSION: Intralesional propranolol
      injection is an alternative and effective method for treatment of infantile
      periocular hemangioma.

PMID- 21887094
TI  - Update on the role of genetics in the onset of age-related macular degeneration.
AB  - Age-related macular degeneration (AMD), akin to other common age-related
      diseases, has a complex pathogenesis and arises from the interplay of genes,
      environmental factors, and personal characteristics. The past decade has seen
      very significant strides towards identification of those precise genetic variants
      associated with disease. That genes encoding proteins of the (alternative)
      complement pathway (CFH, C2, CFB, C3, CFI) are major players in etiology came as
      a surprise to many but has already lead to the development of therapies entering
      human clinical trials. Other genes replicated in many populations ARMS2, APOE,
      variants near TIMP3, and genes involved in lipid metabolism have also been
      implicated in disease pathogenesis. The genes discovered to date can be estimated
      to account for approximately 50% of the genetic variance of AMD and have been
      discovered by candidate gene approaches, pathway analysis, and latterly genome
      wide association studies. Next generation sequencing modalities and meta-analysis
      techniques are being employed with the aim of identifying the remaining rarer
      but, perhaps, individually more significant sequence variations, linked to
      disease status. Complementary studies have also begun to utilize this genetic
      information to develop clinically useful algorithms to predict AMD risk and
      evaluate pharmacogenetics. In this article, contemporary commentary is provided
      on rapidly progressing efforts to elucidate the genetic pathogenesis of AMD as
      the field stands at the end of the first decade of the 21st century.

PMID- 21887096
TI  - Prevention of cataract in diabetic mice by topical pyruvate.
AB  - BACKGROUND: It has been previously reported that oral administration of sodium
      pyruvate inhibits oxidative stress and cataract formation in diabetic animals.
      With a view to exploring the clinical usefulness of these findings, this study
      examined its preventive effect when administered topically as an eye drop.
      METHODS: Diabetes was induced by intraperitoneal injections of streptozotocin. At
      the onset of diabetes, an eye drop preparation containing 2.5% sodium pyruvate
      was administered six times a day at 90-minute intervals. Treatment was continued
      for 6 weeks. Cataract formation was monitored ophthalmoscopically after mydriasis
      with 1% tropicamide eye drops. Subsequently, the treated and untreated diabetic
      animals and the age-matched normal controls were euthanized, their eyes
      enucleated, and the lenses isolated for biochemical assessment of protein
      glycation and glutathione levels. RESULTS: Treatment with pyruvate eye drops was
      found to be significantly effective in inhibiting protein glycation. Glutathione
      levels were also better maintained. In addition, ophthalmoscopic examination
      revealed that the incidence of cataract in the pyruvate-treated group was only
      12% as compared with the untreated diabetics in whom the incidence was 73%.
      Cataracts at this stage were largely equatorial. CONCLUSION: The results
      demonstrate that topical application of pyruvate can potentially be useful in
      attenuating or preventing cataract formation induced by diabetes and other
      conditions of oxidative stress.

PMID- 21887097
TI  - A rare case of zolendronate infusion complication leading to glaucoma filtration
      surgery.
AB  - Zolendronic acid is a nitrogenous biphosphonate commonly used as an intravenous
      infusion for the management of Paget's disease, osteoporosis, and hypercalcemia
      of malignancy. We report a rare and challenging complication of zolendronate
      infusion: unilateral acute anterior uveitis followed by persistently raised
      intraocular pressure despite being on four different classes of antiglaucoma
      medication. The challenge was that the patient required topical steroid to treat
      her uveitis in the background of known glaucoma with corresponding steroid
      response. She eventually underwent a left phacotrabeculectomy augmented with 5
      fluorouracil. Four weeks postoperatively she developed an encapsulated bleb and
      underwent needling with 5-fluorouracil. This case highlights the importance of
      having a high index of suspicion for anterior uveitis in patients with a red and
      painful eye after initiating biphosphonate therapy. Caution should also be
      exercised when prescribing biphosponates to glaucoma patients.

PMID- 21887099
TI  - Acute progression of electrophysiologically affected fellow eye in unilaterally
      symptomatic acute zonal occult outer retinopathy.
AB  - Some patients with acute zonal occult outer retinopathy (AZOOR) show symptomatic
      acute visual impairment in one eye only, but electrophysiological abnormalities
      in both eyes. A 46-year-old female who had noticed paracentral scotoma of her
      right eye six months previously was referred to our hospital. At initial
      examination, her best-corrected visual acuity was 0.7 in the right eye and 1.2 in
      the left. Whereas the full-field rod electroretinogram (ERG) was normal in both
      eyes, the cone response was nonrecordable in the right eye and showed a
      significant decrease in amplitude in the left eye. The 30 Hz flicker ERG showed
      similar results. Multifocal ERG was nonrecordable in the right eye and showed a
      residual response in only the central part of the left. Fourteen months after the
      first visit, the patient presented complaining of acute visual acuity loss in the
      left eye. Visual acuity in her left eye had decreased to 0.01. The multifocal ERG
      was nonrecordable. Although the patient chose oral prednisolone therapy, only
      limited recovery was observed in the patient. Even if only the ERG shows changes
      and there are no other symptoms, ophthalmologists should continue observation in
      view of the possibility of an acute exacerbation.

PMID- 21887100
TI  - Reproducibility of retinal circulation measurements obtained using laser speckle
      flowgraphy-NAVI in patients with glaucoma.
AB  - BACKGROUND: Laser speckle flowgraphy (LSFG) enables noninvasive quantification of
      the retinal circulation in glaucoma patients. In this study, we tested the
      intrasession reproducibility of LSFG-NAVI, a modified LSFG technique. METHODS:
      Sixty-five eyes from 33 subjects (male (M):female (F) = 17:16) with a mean age of
      49.4 +/- 11.2 years were examined in this study. Two parameters indicating
      reproducibility - the coefficient of variation (COV) and the intraclass
      correlation coefficient (ICC) - were analyzed three times on the same day that
      mean blur rate (MBR) was measured using LSFG-NAVI. The sites analyzed were the
      retinal artery and vein, the optic disk, and the choroid. Following
      classification according to the Glaucoma Hemifield Test (GHT; SITA-Standard 30-2
      program), the COV and ICC were examined in patients with (GHT+; 38 eyes, M:F =
      20:18, average age 48.9 +/- 12.8 years) and without (GHT-; 27 eyes, M:F = 13:14,
      average age 50.1 +/- 8.7 years) abnormal glaucomatous visual fields. RESULTS: FOR
      ALL SUBJECTS, THE INTRASESSION REPRODUCIBILITY OF MBR IN THE OPTIC DISK (COV: 3.4
      +/- 2.0; ICC: 0.95) and choroid (COV: 4.7 +/- 3.4; ICC: 0.98) was excellent. The
      reproducibility for the retinal vein (COV: 8.4 +/- 5.6, ICC: 0.90) and retinal
      artery (COV: 10.9 +/- 9.9, ICC: 0.9) was moderate. MBRs in the optic disk had
      good reproducibility in both the GHT+ group (COV: 3.8 +/- 2.0; ICC: 0.97) and the
      GHT- group (COV: 2.9 +/- 2.1; ICC: 0.95). Local assessment of the optic disk in
      normal or glaucoma patients showed that the COVs of the quadrant optic disk areas
      were best in the temporal area of MBR (3.4%, 4.2%, respectively). CONCLUSION:
      LSFG-NAVI showed favorable reproducibility in evaluation of retinal circulation
      of glaucoma patients, particularly in the optic disk and choroid.

PMID- 21887101
TI  - Outcomes of 23-gauge pars plana vitrectomy and internal limiting membrane peeling
      with brilliant blue in macular hole.
AB  - PURPOSE: The evaluation of anatomic and visual outcomes in macular hole cases
      treated with internal limiting membrane (ILM) peeling, brilliant blue (BB), and
      23-gauge pars plana vitrectomy (PPV). MATERIALS AND METHODS: Fifty eyes of 48
      patients who presented between July 2007 and December 2009 with the diagnosis of
      stage 2, 3, or 4 macular holes according to Gass Classification who had undergone
      PPV and ILM peeling were included in this study. Pre- and postoperative macular
      examinations were assessed with spectral-domain optical coherence tomography. 23
      G sutureless PPV and ILM peeling with BB was performed on all patients. RESULTS:
      The mean age of patients was 63.34 +/- 9.6 years. Stage 2 macular hole was
      determined in 17 eyes (34%), stage 3 in 24 eyes (48%), and stage 4 in 9 eyes
      (18%). The mean follow-up time was 13.6 +/- 1.09 months. Anatomic closure was
      detected in 46/50 eyes (92%), whereas, in four cases, macular hole persisted and
      a second operation was not required due to subretinal fluid drainage. At follow
      up after 2 months, persistant macular hole was detected in one case and it was
      closed with reoperation. At 12 months, an increase in visual acuity in 41 eyes
      was observed, while it remained at the same level in six eyes. In three eyes
      visual acuity decreased. There was a postoperative statistically significant
      increase in visual acuity in stage 2 and 3 cases (P < 0.05), however, no increase
      in visual acuity in stage 4 cases was observed. CONCLUSION: PPV and ILM peeling
      in stage 2, 3, and 4 macular hole cases provide successful anatomic outcomes,
      however, in delayed cases, due to photoreceptor loss, it has no effect on
      functional recovery. BB, used for clarity of ILM, may be beneficial due to its
      low retinal toxicity.

PMID- 21887098
TI  - Emerging nonsurgical methods for the treatment of vitreomacular adhesion: a
      review.
AB  - With the dissemination of optical coherence tomography over the past two decades,
      the role of persistent vitreomacular adhesion (VMA) in the development of
      numerous macular pathologies - including idiopathic macular hole, vitreomacular
      traction syndrome, cystoid and diabetic macular edema, neovascularization in
      diabetic retinopathy and retinal vein occlusion, exudative age-related macular
      degeneration, and myopic traction maculopathy - has been established. While
      invasive vitreoretinal procedures have long been utilized to address
      complications related to these disorders, such an approach is hampered by
      incomplete vitreoretinal separation and vitreous removal, surgical complications,
      and high costs. In light of such limitations, investigators have increasingly
      looked to nonsurgical means for the treatment of persistent pathologic VMA. Chief
      among these alternative measures is the intravitreal application of pharmacologic
      agents for the induction of vitreous liquefaction and/or vitreoretinal
      separation, an approach termed pharmacologic vitreolysis. This article aims to
      review the available evidence regarding the use of pharmacologic agents in the
      treatment of VMA-related pathology. In addition, a discussion of vitreous
      molecular organization and principles of physiologic posterior vitreous
      detachment is provided to allow for a consideration of vitreolytic agent mode of
      action and molecular targets.

PMID- 21887103
TI  - Efficacy and safety of prolonged-release melatonin in insomnia patients with
      diabetes: a randomized, double-blind, crossover study.
AB  - BACKGROUND: Diabetes is a major comorbidity in insomnia patients. The efficacy
      and safety of prolonged-release melatonin 2 mg in the treatment of glucose, lipid
      metabolism, and sleep was studied in 36 type 2 diabetic patients with insomnia
      (11 men, 25 women, age 46-77 years). METHODS: In a randomized, double-blind,
      crossover study, the subjects were treated for 3 weeks (period 1) with prolonged
      release melatonin or placebo, followed by a one-week washout period, and then
      crossed over for another 3 weeks (period 2) of treatment with the other
      preparation. All tablets were taken 2 hours before bedtime for a period of 3
      weeks. In an extension period of 5 months, prolonged-release melatonin was given
      nightly to all patients in an open-label design. Sleep was objectively monitored
      in a subgroup of 22 patients using wrist actigraphy. Fasting glucose,
      fructosamine, insulin, C-peptide, triglycerides, total cholesterol, high-density
      and low-density lipoprotein cholesterol, and some antioxidants, as well as
      glycosylated hemoglobin (HbA1c) levels were measured at baseline and at the end
      of the study. All concomitant medications were continued throughout the study.
      RESULTS: No significant changes in serum glucose, fructosamine, insulin, C
      peptide, antioxidant levels or blood chemistry were observed after 3 weeks of
      prolonged-release melatonin treatment. Sleep efficiency, wake time after sleep
      onset, and number of awakenings improved significantly with prolonged-release
      melatonin as compared with placebo. Following 5 months of prolonged-release
      melatonin treatment, mean HbA1c (+/-standard deviation) was significantly lower
      than at baseline (9.13% +/- 1.55% versus 8.47% +/- 1.67%, respectively, P =
      0.005). CONCLUSION: Short-term use of prolonged-release melatonin improves sleep
      maintenance in type 2 diabetic patients with insomnia without affecting glucose
      and lipid metabolism. Long-term prolonged-release melatonin administration has a
      beneficial effect on HbA1c, suggesting improved glycemic control.

PMID- 21887102
TI  - Update on the management of diabetic polyneuropathies.
AB  - The prevalence of diabetic polyneuropathy (DPN) can approach 50% in subjects with
      longer-duration diabetes. The most common neuropathies are generalized
      symmetrical chronic sensorimotor polyneuropathy and autonomic neuropathy. It is
      important to recognize that 50% of subjects with DPN may have no symptoms and
      only careful clinical examination may reveal the diagnosis. DPN, especially
      painful diabetic peripheral neuropathy, is associated with poor quality of life.
      Although there is a better understanding of the pathophysiology of DPN and the
      mechanisms of pain, treatment remains challenging and is limited by variable
      efficacy and side effects of therapies. Intensification of glycemic control
      remains the cornerstone for the prevention or delay of DPN but optimization of
      other traditional cardiovascular risk factors may also be of benefit. The
      management of DPN relies on its early recognition and needs to be individually
      based on comorbidities and tolerability to medications. To date, most
      pharmacological strategies focus upon symptom control. In the management of pain,
      tricyclic antidepressants, selective serotonin noradrenaline reuptake inhibitors,
      and anticonvulsants alone or in combination are current first-line therapies
      followed by use of opiates. Topical agents may offer symptomatic relief in some
      patients. Disease-modifying agents are still in development and to date,
      antioxidant alpha-lipoic acid has shown the most promising effect. Further
      development and testing of therapies based upon improved understanding of the
      complex pathophysiology of this common and disabling complication is urgently
      required.

PMID- 21887104
TI  - Effect of weight loss on adipokine levels in obese patients.
AB  - BACKGROUND: Adipose tissue functions as an endocrine organ by releasing
      adipokines which have important roles in the regulation of inflammation and
      insulin sensitivity. Although there is evidence of improvement in circulating
      levels of adipokines with weight loss, few studies relate such changes to
      specific diets. We investigated the effects of weight loss achieved by two
      different diets on circulating adipokine levels in obese individuals. METHODS: A
      total of 120 obese patients (body mass index >= 35 kg/m(2)) underwent a three
      month screening period on a low-fat, reduced-calorie diet. Patients failing to
      achieve a 5% weight loss using this approach were randomly allocated to either a
      low carbohydrate/high protein diet (n = 17) or to a commercial very low calorie
      diet (LighterLife((r)), n = 14) for a period of nine months. RESULTS: At nine
      months, a significant weight loss was only maintained for Lighter-Life((r)) (
      32.3 +/- 22.7 kg, P < 0.0001) but not on the low carbohydrate/high protein diet.
      Changes in adiponectin (15.8 +/- 17.1 ng/mL versus -0.8 +/- 6.2 ng/mL, P = 0.003)
      and leptin (-17.6 +/- 24.3 ng/mL versus -3.0 +/- 9.2 ng/mL, P = 0.049) at nine
      months were significantly greater for LighterLife((r)) than for the low
      carbohydrate/high protein diet, which may reflect greater weight loss and
      decrease in fat mass. Changes in tumor necrosis factor-alpha, interleukin-6, and
      plasminogen activator inhibitor type 1 did not differ significantly between the
      dietary interventions at nine months. CONCLUSION: A significant weight loss of
      23.8% from baseline weight was observed using a very low calorie diet and
      resulted in significant improvements in circulating levels of leptin, plasminogen
      activator inhibitor type 1, and adiponectin, which are likely to be due to weight
      loss and not macronutrient intake.

PMID- 21887107
TI  - Hypotensive response after water-walking and land-walking exercise sessions in
      healthy trained and untrained women.
AB  - BACKGROUND: The aim of this study was to compare post-exercise hypotension after
      acute sessions of water-walking and land-walking in healthy trained and untrained
      women. METHODS: Twenty-three untrained (n = 12) and trained (n = 11) normotensive
      women performed two walking sessions in water and on land at 40% of peak VO(2)
      for 45 minutes. Systolic and diastolic blood pressure and mean arterial pressure
      were measured 15, 30, 45, and 60 minutes after the exercise sessions. RESULTS: No
      differences were found between the groups for age and anthropometric parameters,
      but peak VO(2) for the trained women (45 +/- 8 mL/kg/minute) was higher than for
      the untrained women (31 +/- 3 mL/kg/minute). No differences were found between
      the groups with regard to systolic and diastolic blood pressure and mean arterial
      pressure after water immersion. The heart rate in the trained group (62 +/- 3
      beats per minute [bpm]) was significantly lower (P < 0.05) than in the untrained
      group (72 +/- 4 bpm) on land, and after water immersion, this difference
      disappeared (58 +/- 5 bpm in the trained women and 66 +/- 5 bpm in the untrained
      women). Sixty minutes after water-walking, systolic blood pressure (108 +/- 8
      mmHg vs 97 +/- 3 mmHg), diastolic blood pressure (69 +/- 5 mmHg vs 62 +/- 5
      mmHg), and mean arterial pressure (82 +/- 6 mmHg vs 74 +/- 4 mmHg) decreased
      significantly with rest in the untrained group, and no differences were found
      after land-walking. In the trained group, significant (P < 0.05) differences were
      found only for systolic blood pressure (110 +/- 9 mmHg vs 100 +/- 9 mmHg) after
      60 minutes of water-walking; decreases in systolic blood pressure were found
      after 45 minutes (99 +/- 7 mmHg) and 60 minutes (99 +/- 6 mmHg) compared with
      rest (107 +/- 5 mmHg) after land-walking. CONCLUSION: Single water-walking and
      land-walking sessions induced important hypotension following exercise.
      Additionally, walking performed in chest-deep water has a better effect on
      exercise-induced hypotension in untrained healthy women than walking at a similar
      intensity on land.

PMID- 21887108
TI  - Subjective food hypersensitivity: assessment of enterochromaffin cell markers in
      blood and gut lavage fluid.
AB  - BACKGROUND: Food hypersensitivity is commonly suspected, but seldom verified.
      Patients with subjective food hypersensitivity suffer from both intestinal and
      extraintestinal health complaints. Abnormalities of the enterochromaffin cells
      may play a role in the pathogenesis. The aim of this study was to investigate
      enterochromaffin cell function in patients with subjective food hypersensitivity
      by measuring serum chromogranin A (CgA) and 5-hydroxytryptamine (5-HT, serotonin)
      in gut lavage fluid. METHODS: Sixty-nine patients with subjective food
      hypersensitivity were examined. Twenty-three patients with inflammatory bowel
      disease and 35 healthy volunteers were included as comparison groups. CgA was
      measured in serum by enzyme-linked immunosorbent assay. Gut lavage fluid was
      obtained by administering 2 L of polyethylene glycol solution intraduodenally.
      The first clear fluid passed per rectum was collected and 5-HT was analyzed by
      liquid chromatography tandem mass spectrometry. RESULTS: Serum levels of CgA were
      significantly lower in patients with subjective food hypersensitivity than in
      healthy controls (P = 0.04). No differences were found in 5-HT levels in gut
      lavage fluid between patients with subjective food hypersensitivity and the
      control groups. There was no correlation between serum CgA and gut lavage 5-HT.
      CONCLUSION: Decreased blood levels of CgA suggest neuroendocrine alterations in
      patients with subjective food hypersensitivity. However, 5-HT levels in gut
      lavage fluid were normal.

PMID- 21887109
TI  - Diurnal salivary cortisol concentrations in Parkinson's disease: increased total
      secretion and morning cortisol concentrations.
AB  - BACKGROUND: Parkinson's disease (PD) is a chronic neurodegenerative disorder.
      There is limited knowledge about the function of the hypothalamic-pituitary
      adrenal axis in PD. The primary aim of this prospective study was to analyze
      diurnal salivary cortisol concentrations in patients with PD and correlate these
      with age, gender, body mass index (BMI), duration of PD, and pain. The secondary
      aim was to compare the results with a healthy reference group. METHODS: Fifty
      nine PD patients, 35 women and 24 men, aged 50-79 years, were recruited. The
      reference group comprised healthy individuals matched for age, gender, BMI, and
      time point for sampling. Salivary cortisol was collected at 8 am, 1 pm, and 8 pm,
      and 8 am the next day using cotton-based Salivette((r)) tubes and analyzed using
      Spectria((r)) Cortisol I(125). A visual analog scale was used for estimation of
      pain. RESULTS: The median cortisol concentration was 16.0 (5.8-30.2) nmol/L at 8
      am, 5.8 (3.0-16.4) at 1 pm, 2.8 (1.6-8.0) at 8 pm, and 14.0 (7.5-28.7) at 8 am
      the next day. Total secretion and rate of cortisol secretion during the day (8 am
      8 pm) and the concentration of cortisol on the next morning were lower (12.5
      nmol/L) in the reference group. No significant correlations with age, gender,
      BMI, duration of PD, Hoehn and Yahr score, Unified Parkinson's Disease Rating
      Scale III score, gait, pain, or cortisol concentrations were found. CONCLUSION:
      The neurodegenerative changes in PD does not seem to interfere with the
      hypothalamic-pituitary-adrenal axis. Salivary cortisol concentrations in PD
      patients were increased in the morning compared with the reference group, and
      were not influenced by motor dysfunction, duration of disease, or coexistence of
      chronic or acute pain.

PMID- 21887110
TI  - Nosocomial infections: knowledge and source of information among clinical health
      care students in Ghana.
AB  - BACKGROUND: This study determined and compared the knowledge of nosocomial
      infections among clinical health care students at the College of Health Sciences,
      University of Ghana. METHODS: Two hundred undergraduate health care students from
      four academic programs participated in the study. The study sample was drawn from
      each academic program by a simple random sampling technique using the class
      directory from each course. The Infection Control Standardized Questionnaire
      (ICSQ) was used to assess the knowledge of students about three main domains, ie,
      hand hygiene, nosocomial infections, and standard precautions. A maximum score of
      50 was obtainable, and respondents with scores >=70% were classified as having a
      satisfactory knowledge. The response on each item was coded numerically to
      generate data for statistical analysis. Comparison of knowledge on the domains
      among categories of students was assessed using the Kruskal-Wallis test, while
      associations between courses of study and knowledge about nosocomial infections
      were determined using the Chi-square test. All statistical tests had a
      significant level of 5% (P < 0.05) RESULTS: Overall mean percentage score of the
      participants on ICSQ was 65.4 +/- 2.58, with medical, physiotherapy, radiography,
      and nursing students recording mean percentage scores of 70.58 +/- 0.62, 65.02 +/
      2.00, 64.74 +/- 1.19, and 61.31 +/- 2.35, respectively. The main source of
      information about the prevention of nosocomial infections as cited by
      participants was their routine formal training in class. There was no significant
      association (P > 0.05) between course of study and knowledge of students about
      preventive measures for nosocomial infections. CONCLUSION: The students sampled
      demonstrated moderate knowledge of nosocomial infections and this was acquired
      largely through formal classroom training. These findings underscore the need for
      more emphasis on education about this important source of infection in the
      clinical training curriculum.

PMID- 21887111
TI  - The RT-18: a new screening tool to assess young adult risk-taking behavior.
AB  - Risk-taking behavior is a major determinant of health and plays a central role in
      various diseases. Therefore, a brief questionnaire was developed to assess risk
      taking among young adults with known different levels of risk-taking behavior
      (social drinkers and recreational drug users). In Study 1, N = 522 university
      students completed the RT-18 risk taking questionnaire. N = 100 students were
      retested after 2 to 4 weeks and performed the Cambridge Gambling Task (CGT). Mean
      RT-18 score was 7.69 and Cronbach's alpha was 0.886. The test-retest reliability
      was r = 0.94. Significant correlation was found between the RT-18 score and CGT
      scores of risk taking, bet proportion, and risk adjustment. In Study 2, N = 7834
      young adult social drinkers, and recreational drug users, mean RT-18 score was
      9.34 and Cronbach's alpha was 0.80. Factor analysis showed that the RT-18
      comprises two factors assessing level of risk-taking behavior and risk
      assessment. Men scored significantly higher than women on the RT-18. Recreational
      drug users had significantly higher scores when compared to social drinkers. In
      Study 3 of N = 1000 students, construct validity was confirmed by showing that
      the RT-18 outcome correlates significantly with scores on the Stimulating
      Instrumental Risk Inventory. In conclusion, the RT-18 is a valid and reliable
      screening tool to differentiate levels of risk-taking behavior. This short scale
      is quick and practical to administer, imposing minimal demands on participants.
      The RT-18 is able to differentiate risk taking and risk assessment which can help
      target appropriate intervention strategies.

PMID- 21887112
TI  - Key role of congestion in natural history of heart failure.
AB  - The natural course of heart failure with decreased and preserved systolic
      function is almost identical. The current concept of heart failure where
      decreased cardiac output plays the major role does not explain this similarity.
      We suggest a revised concept of heart failure where congestion plays the leading
      role. While congestion is almost invariably present in heart failure with normal
      and with reduced systolic function, the low output syndrome is only present in
      heart failure with reduced systolic function. The small difference in morbidity
      and mortality in favor of heart failure with preserved systolic function reflects
      the contribution of low output syndrome to the natural course of the disease.
      Congestion can result from low output or from multiple other conditions, but
      severity of congestion is the major determinant of progression of heart failure.

PMID- 21887113
TI  - ABC of flexible cystoscopy for junior trainee and general practitioner.
AB  - INTRODUCTION: Flexible cystoscopy is a diagnostic procedure usually performed
      under local anesthesia and has been used in the outpatient setting since the
      1980s. METHODS: We performed an electronic search of MEDLINE((r)) and the
      Cochrane Central Search Library between 1990 and 2010. Duplicate references were
      removed. One reviewer extracted the publications relevant to general clinical
      practice. RESULTS: MEDLINE search using the MeSH (Medical Subject Headings) words
      "flexible" and "cystoscopy" revealed 274 titles, and there were 42 titles in the
      Cochrane Central Search Library. However, interestingly, only 13 published papers
      addressing the clinical practice of flexible cystoscopy in the English literature
      were identified. CONCLUSIONS: Flexible cystoscopy is a real revolution in the
      field of diagnostic urology.

PMID- 21887114
TI  - Adjusting wheal size measures to correct atopy misclassification.
AB  - PURPOSE: Skin prick testing (SPT) is fundamental to the practice of clinical
      allergy identifying relevant allergens and predicting the clinical expression of
      disease. Wheal sizes on SPT are used to identify atopic cases, and the cut-off
      value for a positive test is commonly set at 3 mm. However, the measured wheal
      sizes do not solely reflect the magnitude of skin reaction to allergens, but also
      skin reactivity (reflected in the size of histamine reaction) and other random or
      non-random factors. We sought to estimate wheal sizes exclusively due to skin
      response to allergens and propose gender-specific cutoff points of atopy.
      METHODS: We developed a Bayesian method to adjust observed wheal sizes by
      excluding histamine and other factor effects, based on which revised cutoff
      points are proposed for males and females, respectively. The method is then
      applied to and intensively evaluated using a study population aged 18, at a
      location on the Isle of Wight in the United Kingdom. To evaluate the proposed
      approach, two sample t-tests for population means and proportion tests are
      applied. RESULTS: Four common aeroallergens, house dust mite (HDM), grass pollen,
      dog dander, and alternaria are considered in the study. Based on 3 mm cutoff,
      males tend to be more atopic than females (P-values are between 0.00087 and
      0.062). After applying the proposed methods to adjust wheal sizes, our findings
      suggest that misclassifications of atopy occur more often in males. Revised
      allergen-specific cutoff values are proposed for each gender. CONCLUSION: To
      reduce the gender discrepancy, we may have two potentially convenient solutions.
      One way is to apply allergen-specific and gender-specific cutoff values following
      the proposed method. Alternatively, we can revise the concentration of allergens
      in the SPT solutions but keep the cutoff values unchanged, which may be more
      convenient to clinicians.

PMID- 21887115
TI  - Evaluating risk factors for protein-energy malnutrition in children under the age
      of six years: a case-control study from Iran.
AB  - INTRODUCTION: Protein-energy malnutrition is one of the most important public
      health problems in Iran. It not only accounts for more than half of child
      mortality but can also produce somatic and mental impairment in survivors. The
      main aim of this study was to identify risk factors for protein-energy
      malnutrition in children under 6 years of age in Namin city. METHODS: This was a
      population-based, multicenter case-control study. Seventy-six children with
      malnutrition and 76 children without malnutrition were randomly recruited for
      case and control groups. The prevalence of risk factors in the two groups was
      compared. Data were gathered from a health center database and interviews with
      mothers and health workers. The Wilcoxon signed-rank test and logistic regression
      were used for data analysis. RESULTS: Female gender, poverty, short maternal
      height, and use of unhygienic latrines in the home were significantly associated
      with childhood malnutrition (P < 0.05). CONCLUSION: The results of this study
      indicate four main factors (poverty, small maternal height, female gender, and
      absence of hygienic latrines in the home) as underlying factors in malnutrition
      of children under the age of 6 years.

PMID- 21887116
TI  - An eight-week yoga intervention is associated with improvements in pain,
      psychological functioning and mindfulness, and changes in cortisol levels in
      women with fibromyalgia.
AB  - OBJECTIVES: Fibromyalgia (FM) is a chronic condition characterized by widespread
      musculoskeletal pain, fatigue, depression, and hypocortisolism. To date,
      published studies have not investigated the effects of yoga on cortisol in FM.
      This pilot study used a time series design to evaluate pain, psychological
      variables, mindfulness, and cortisol in women with FM before and after a yoga
      intervention. METHODS: Participants (n = 22) were recruited from the community to
      participate in a 75 minute yoga class twice weekly for 8 weeks. Questionnaires
      concerning pain (intensity, unpleasantness, quality, sum of local areas of pain,
      catastrophizing, acceptance, disability), anxiety, depression, and mindfulness
      were administered pre-, mid- and post-intervention. Salivary cortisol samples
      were collected three times a day for each of two days, pre- and post
      intervention. RESULTS: Repeated measures analysis of variance (ANOVA) revealed
      that mean +/- standard deviation (SD) scores improved significantly (p < 0.05)
      from pre- to post-intervention for continuous pain (pre: 5.18 +/- 1.72; post:
      4.44 +/- 2.03), pain catastrophizing (pre: 25.33 +/- 14.77; post: 20.40 +/-
      17.01), pain acceptance (pre: 60.47 +/- 23.43; post: 65.50 +/- 22.93), and
      mindfulness (pre: 120.21 +/- 21.80; post: 130.63 +/- 20.82). Intention-to-treat
      analysis showed that median AUC for post-intervention cortisol (263.69) was
      significantly higher (p < 0.05) than median AUC for pre-intervention levels
      (189.46). Mediation analysis revealed that mid-intervention mindfulness scores
      significantly (p < 0.05) mediated the relationship between pre- and post
      intervention pain catastrophizing scores. DISCUSSION: The results suggest that a
      yoga intervention may reduce pain and catastrophizing, increase acceptance and
      mindfulness, and alter total cortisol levels in women with FM. The changes in
      mindfulness and cortisol levels may provide preliminary evidence for mechanisms
      of a yoga program for women with FM. Future studies should use an RCT design with
      a larger sample size.

PMID- 21887117
TI  - Tapentadol in the management of chronic low back pain: a novel approach to a
      complex condition?
AB  - Chronic pain affects approximately 1 in 5 people in Europe, and around half of
      sufferers receive inadequate pain management. The most common location is the
      lower back. Pharmacological treatment of this condition is challenging because of
      the range of causative mechanisms and the difficulty of balancing analgesic
      efficacy and tolerability. An international panel of clinical pain specialists
      met in September, 2009, to discuss the treatment of chronic low back pain, and to
      review preclinical and clinical data relating to the new analgesic, tapentadol. A
      lack of consensus exists on the best treatment for low back pain. The range of
      regularly prescribed pharmacological agents extends from nonopioids (paracetamol,
      NSAIDs, and COX-2 inhibitors) to opioids, antidepressants and anticonvulsants.
      Pain relief may be compromised, however, by an undetected neuropathic component
      or intolerable side effects. Treatment is potentially life-long and effective
      analgesics are urgently needed, with demonstrable long-term safety. Combining
      separate agents with different mechanisms of action could overcome the
      limitations of present pharmacological therapy, but clinical evidence for this
      approach is currently lacking. Tapentadol combines MU-opioid agonism with
      noradrenaline reuptake inhibition in a single molecule. There is strong evidence
      of synergistic antinociception between these two mechanisms of action. In
      preclinical and clinical testing, tapentadol has shown efficacy against both
      nociceptive and neuropathic pain. Preclinical data indicate that tapentadol's MU
      opioid agonism makes a greater contribution to analgesia in acute pain, while
      noradrenaline reuptake inhibition makes a greater contribution in chronic
      neuropathic pain models. Tapentadol also produces fewer adverse events than
      oxycodone at equianalgesic doses, and thus may have a 'MU-sparing effect'.
      Current evidence indicates that tapentadol's efficacy/tolerability ratio may be
      better than those of classical opioids. However, further research is needed to
      establish its role in pain management.

PMID- 21887119
TI  - Pain in patients with multiple sclerosis: a complex assessment including
      quantitative and qualitative measurements provides for a disease-related
      biopsychosocial pain model.
AB  - BACKGROUND: Pain of various causes is a common phenomenon in patients with
      Multiple Sclerosis (MS). A biopsychosocial perspective has proven a useful
      theoretical construct in other chronic pain conditions and was also started in
      MS. To support such an approach, we aimed to investigate pain in MS with special
      emphasis on separating quantitative and qualitative aspects, and its
      interrelation to behavioral and physical aspects. MATERIALS AND METHODS: Pain
      intensity (NRS) and quality (SES) were measured in 38 consecutive outpatients
      with MS (mean age, 42.0 +/- 11.5 years, 82% women). Pain-related behavior (FSR),
      health care utilization, bodily complaints (GBB-24) and fatigue (WEIMuS) were
      assessed by questionnaires, and MS-related neurological impairment by a
      standardized neurological examination (EDSS). RESULTS: Mean pain intensity was
      4.0 (range, 0-10) and mean EDSS 3.7 (range, 0-8) in the overall sample. Currently
      present pain was reported by 81.6% of all patients. Disease duration and EDSS did
      not differ between patients with and without pain and were not correlated to
      quality or intensity of pain. Patients with pain had significantly higher scores
      of musculoskeletal complaints, but equal scores of exhaustion, gastrointestinal
      and cardiovascular complaints. Pain intensity correlated only with physical
      aspects, whereas quality of pain was additionally associated with increased
      avoidance, resignation and cognitive fatigue. CONCLUSION: As in other conditions,
      pain in MS must be assessed in a multidimensional way. Further research should be
      devoted to adapt existing models to a MS-specific model of pain.

PMID- 21887118
TI  - Tapentadol extended-release for treatment of chronic pain: a review.
AB  - Tapentadol is a centrally acting analgesic with a dual mechanism of action of mu
      receptor agonism and norepinephrine reuptake inhibition. Tapentadol immediate
      release is approved by the US Food and Drug Administration for the management of
      moderate-to-severe acute pain. It was developed to decrease the intolerability
      issue associated with opioids. Tapentadol extended-release has a 12-hour duration
      of effect, and has recently been evaluated for pain in patients with chronic
      osteoarthritis, low back pain, and pain associated with diabetic peripheral
      neuropathy. Tapentadol extended-release was found to provide safe and highly
      effective analgesia for the treatment of chronic pain conditions, including
      moderate-to-severe chronic osteoarthritis pain and low back pain. Initial trials
      demonstrating efficacy in neuropathic pain suggest that tapentadol has comparable
      analgesic effectiveness and better gastrointestinal tolerability than opioid
      comparators, and demonstrates effectiveness in settings of inflammatory, somatic,
      and neuropathic pain. Gastrointestinal intolerance and central nervous system
      effects were the major adverse events noted. Tapentadol will need to be
      rigorously tested in chronic neuropathic pain, cancer-related pain, and cancer
      related neuropathic pain.

PMID- 21887120
TI  - Pain relief in labor: a survey of awareness, attitude, and practice of health
      care providers in Zaria, Nigeria.
AB  - BACKGROUND: The purpose of this study was to assess the attitudes of maternal
      health care providers to pain relief during labor in Zaria, Nigeria. METHODS:
      This was a multicenter, collaborative, cross-sectional pilot study of provider
      perspectives concerning pain relief during labor. A structured, self
      administered, questionnaire was completed by 95 consenting maternal health care
      providers at three high-volume facilities in Zaria, an ancient northern Nigerian
      city. Descriptive statistics was performed on the data. RESULTS: Most respondents
      (94.8%) agreed that pain relief is needed during labor. Only 2.1% of respondents
      were undecided about the provision of pain relief during labor and 3.2% were of
      the opinion that pain relief was not necessary during labor. Most respondents
      (93.7%) had attended a woman in labor in the 4 weeks preceding the survey. Of
      these, 56.8% had counseled a parturient in labor. Most of the counseling (42.1%)
      took place during labor. Less than half of the respondents (48.4%) had
      administered pain relief in labor in the preceding 4 weeks and systemic opioids
      was the most commonly form of pain relief. Among the respondents who did not
      offer pain relief agents in labor, the majority (54.5%) had no reason for not
      offering it. Unavailability of methods, inability to afford the cost of pain
      relief, lack of knowledge and skills, as well as lack of essential equipment to
      provide the procedure were also given by respondents as reasons for not offering
      pain relief. CONCLUSION: Even though maternal health care providers in this
      environment have a positive attitude to pain relief in labor, most women go
      through labor without the benefit of analgesia. There exists a gap between
      provider attitudes to pain relief in labor and practice of the same, with many
      providers having no genuine reason(s) for not offering pain relief to their
      clients during labor. Providers need to align their practice to their attitudes,
      and need to be helped to do this through training as well as enhancing their
      ability to think critically about their practice.

PMID- 21887121
TI  - Understanding auditory spectro-temporal receptive fields and their changes with
      input statistics by efficient coding principles.
AB  - Spectro-temporal receptive fields (STRFs) have been widely used as linear
      approximations to the signal transform from sound spectrograms to neural
      responses along the auditory pathway. Their dependence on statistical attributes
      of the stimuli, such as sound intensity, is usually explained by nonlinear
      mechanisms and models. Here, we apply an efficient coding principle which has
      been successfully used to understand receptive fields in early stages of visual
      processing, in order to provide a computational understanding of the STRFs.
      According to this principle, STRFs result from an optimal tradeoff between
      maximizing the sensory information the brain receives, and minimizing the cost of
      the neural activities required to represent and transmit this information. Both
      terms depend on the statistical properties of the sensory inputs and the noise
      that corrupts them. The STRFs should therefore depend on the input power spectrum
      and the signal-to-noise ratio, which is assumed to increase with input intensity.
      We analytically derive the optimal STRFs when signal and noise are approximated
      as Gaussians. Under the constraint that they should be spectro-temporally local,
      the STRFs are predicted to adapt from being band-pass to low-pass filters as the
      input intensity reduces, or the input correlation becomes longer range in sound
      frequency or time. These predictions qualitatively match physiological
      observations. Our prediction as to how the STRFs should be determined by the
      input power spectrum could readily be tested, since this spectrum depends on the
      stimulus ensemble. The potentials and limitations of the efficient coding
      principle are discussed.

PMID- 21887123
TI  - GONADAL HORMONE INDEPENDENT SEX DIFFERENCES IN STEROIDOGENIC FACTOR 1 KNOCKOUT
      MICE BRAIN.
AB  - Sex differences in brain morphology have been described in a number of species
      including humans. Gonadal hormones were shown to provide a major influence on
      brain sexual differentiation more than 50 years ago. A growing number of studies
      is providing evidence for roles of genetic factors, in particular sex chromosome
      complement, on brain sexual differentiation in mammals. In this review, hormone
      independent brain sexual differentiation, with the emphasis on mice with a
      disruption of the SF-1 gene (SF-1 knockout, SF-1 KO) are discussed.

PMID- 21887124
TI  - Addiction and sociality: Perspectives from methamphetamine users in suburban USA.

PMID- 21887125
TI  - Biohybrid Carbon Nanotube/Agarose Fibers for Neural Tissue Engineering.
AB  - We report a novel approach for producing carbon nanotube fibers (CNF) composed
      with the polysaccharide agarose. Current attempts to make CNF's require the use
      of a polymer or precipitating agent in the coagulating bath that may have
      negative effects in biomedical applications. We show that by taking advantage of
      the gelation properties of agarose one can substitute the bath with distilled
      water or ethanol and hence reduce the complexity associated with alternating the
      bath components or the use of organic solvents. We also demonstrate that these
      CNF can be chemically functionalized to express biological moieties through
      available free hydroxyl groups in agarose. We corroborate that agarose CNF are
      not only conductive and nontoxic, but their functionalization can facilitate cell
      attachment and response both in vitro and in vivo. Our findings suggest that
      agarose/CNT hybrid materials are excellent candidates for applications involving
      neural tissue engineering and biointerfacing with the nervous system.

PMID- 21887126
TI  - Primary gastrointestinal diffuse large B cell lymphoma presenting with cold
      agglutinin disease.
AB  - Cold agglutinin disease (CAD) is an autoimmune hemolytic anemia (AIHA) generally
      caused by IgM autoantibodies which exhibit maximal reactivity at 4 degrees C. CAD
      can be idiopathic or secondary to some diseases and/or conditions. Only a
      minority of cases of secondary AIHA in non-Hodgkin's lymphoma (NHL) are
      associated with cold antibodies. Diffuse large B cell lymphoma (DLBCL) is the
      most common subtype of NHLs with a proportion of nearly 30% of all adult cases.
      40% of patients with DLBCL have an extranodal disease or at least disease
      initially confined to extranodal sites. The most common extranodal site is the
      gastrointestinal tract. We present a patient with primary gastrointestinal DLBCL
      who presented with CAD and was treated with a CHOP-Rituximab regimen.

PMID- 21887127
TI  - Endoscopic Management of Gastric Polyp with Outlet Obstruction without
      Polypectomy.
AB  - Although gastric polyp is usually an incidental endoscopic finding, large-sized
      polyps can cause symptoms ranging from epigastralgia to bleeding from ulcerated
      polyps and gastric outlet obstruction. Although the gold standard of treatment is
      removal of the polyp either through endoscopic polypectomy or surgical excision,
      complications associated with these procedures cannot be ignored. The risk
      becomes a major concern for patients at high risk for surgery when complications
      arise. We describe a debilitated 74-year-old woman who presented with early
      satiety, intermittent postprandial nausea and vomiting for three months. Upper
      endoscopy revealed a 2.5 cm pedunculated polyp over the gastric antrum causing
      intermittent obstruction. Considering her high risk for polypectomy, detachable
      snaring was performed without polypectomy in an outpatient setting. The patient
      was complication-free with complete relief of obstructive symptoms one week after
      the procedure. Subsequent follow-ups showed satisfactory healing without signs of
      mucosal disruption or recurrence. The results suggest that detachable snaring
      without polypectomy may be a therapeutic option for high-risk patients with
      benign symptomatic gastric polyps.

PMID- 21887128
TI  - Acute Intrathoracic Gastric Volvulus due to Diaphragmatic Hernia: A Rare
      Emergency Easily Overlooked.
AB  - Acute intrathoracic gastric volvulus occurs when the stomach undergoes
      organoaxial torsion in the chest due to either concomitant enlargement of the
      hiatus or a diaphragmatic hernia. Iatrogenic diaphragmatic hernia can occur after
      hiatal hernia repair and other surgical procedures, such as nephrectomy,
      esophagogastrectomy and splenopancreatectomy. We describe a 49-year-old woman who
      presented to our emergency department with acute moderate epigastric soreness and
      vomiting. She had undergone extensive gynecologic surgery including splenectomy 1
      year before. The chest radiograph obtained in the emergency department
      demonstrated an elevated gastric air-fluid level in the left lower lung field. An
      urgent gastroscopy showed twisted structural abnormality of the stomach body. A
      computed tomography scan demonstrated the distended stomach, located in the left
      lower hemithorax through a left diaphragmatic defect. Emergent transthoracic
      repair was performed. Postoperative recovery was uneventful, and the patient did
      not experience any pain or difficulty with eating.

PMID- 21887129
TI  - A case of ischemic duodenitis associated with superior mesenteric artery syndrome
      caused by an abdominal aortic aneurysm.
AB  - A 74-year-old woman was admitted to our hospital with upper abdominal pain and
      bloody vomiting. An abdominal aneurysm compressed the third portion of the
      duodenum and the second portion of duodenum was distended with thickened walls as
      in superior mesenteric artery syndrome. Endoscopic examination showed an
      edematous mucosa with hemorrhagic erosions, shallow longitudinal ulcers, and star
      shaped ulcers in the duodenum. We diagnosed this case as ischemic duodenitis
      associated with superior mesenteric artery syndrome caused by compression by an
      abdominal aortic aneurysm. The symptoms improved on treatment with bowel rest,
      total parenteral nutrition and administration of a proton pump inhibitor. We
      present here a rare case of ischemic duodenitis and summarize the previous
      medical literature on the disease.

PMID- 21887130
TI  - Discounting in Pigeons When the Choice is between Two Delayed Rewards:
      Implications for Species Comparisons.
AB  - Studies of delay discounting typically have involved choices between smaller,
      immediate outcomes and larger, delayed outcomes. In a study of delay discounting
      in humans, Green et al. (2005) added a period of time prior to both outcomes,
      creating a delay common to both. They found that the subjective value of the more
      delayed reward was well described by a hyperboloid discounting function and that
      the degree to which that outcome was discounted decreased as the common delay
      increased. In two experiments, we examined the effect of adding a common delay on
      the discounting of food rewards in pigeons. In Experiment 1, an adjusting-amount
      procedure was used to establish discounting functions when the common delay was
      0, 3, 5, and 10 s, and different stimuli signaled time to the smaller, sooner and
      larger, later rewards. In contrast to humans, the pigeons showed increases in the
      degree of discounting when a common delay was added. In Experiment 2, the delay
      common to both rewards and the delay unique to the larger, later reward were each
      specifically signaled. With this procedure, the degree of discounting decreased
      as the common delay increased, a result consistent with that obtained with humans
      (Green et al., 2005). These findings reveal fundamental similarities between
      pigeons' and humans' choice behavior, and provide strong interspecies support for
      the hypothesis that choice between delayed outcomes is based on comparison of
      their hyperbolically discounted present subjective values.

PMID- 21887132
TI  - Obsessive-compulsive disorder and memory-mixing in temporal comparison: is
      implicit learning the missing link?

PMID- 21887133
TI  - Time for zebrafish.

PMID- 21887134
TI  - Defining the contributions of network clock models to millisecond timing.

PMID- 21887131
TI  - Neurochemical characterization of the tree shrew dorsal striatum.
AB  - The striatum is a major component of the basal ganglia and is associated with
      motor and cognitive functions. Striatal pathologies have been linked to several
      disorders, including Huntington's, Tourette's syndrome, obsessive-compulsive
      disorders, and schizophrenia. For the study of these striatal pathologies
      different animal models have been used, including rodents and non-human primates.
      Rodents lack on morphological complexity (for example, the lack of well defined
      caudate and putamen nuclei), which makes it difficult to translate data to the
      human paradigm. Primates, and especially higher primates, are the closest model
      to humans, but there are ever-increasing restrictions to the use of these animals
      for research. In our search for a non-primate animal model with a striatum that
      anatomically (and perhaps functionally) can resemble that of humans, we turned
      our attention to the tree shrew. Evolutionary genetic studies have provided
      strong data supporting that the tree shrews (Scadentia) are one of the closest
      groups to primates, although their brain anatomy has only been studied in detail
      for specific brain areas. Morphologically, the tree shrew striatum resembles the
      primate striatum with the presence of an internal capsule separating the caudate
      and putamen, but little is known about its neurochemical composition. Here we
      analyzed the expression of calcium-binding proteins, the presence and
      distribution of the striosome and matrix compartments (by the use of calbindin,
      tyrosine hydroxylase, and acetylcholinesterase immunohistochemistry), and the
      GABAergic system by immunohistochemistry against glutamic acid decarboxylase and
      Golgi impregnation. In summary, our results show that when compared to primates,
      the tree shrew dorsal striatum presents striking similarities in the distribution
      of most of the markers studied, while presenting some marked divergences when
      compared to the rodent striatum.

PMID- 21887135
TI  - Origin and evolution of deep brain stimulation.
AB  - This paper briefly describes how the electrical stimulation, used since antiquity
      to modulate the nervous system, has been a fundamental tool of neurophysiologic
      investigation in the second half of the eighteenth century and was subsequently
      used by the early twentieth century, even for therapeutic purposes. In mid
      twentieth century the advent of stereotactic procedures has allowed the drift
      from lesional to stimulating technique of deep nuclei of the brain for
      therapeutic purposes. In this way, deep brain stimulation (DBS) was born, that,
      over the last two decades, has led to positive results for the treatment of
      medically refractory Parkinson's disease, essential tremor, and dystonia. In
      recent years, the indications for therapeutic use of DBS have been extended to
      epilepsy, Tourette's syndrome, psychiatric diseases (depression, obsessive
      compulsive disorder), some kinds of headache, eating disorders, and the minimally
      conscious state. The potentials of the DBS for therapeutic use are fascinating,
      but there are still many unresolved technical and ethical problems, concerning
      the identification of the targets for each disease, the selection of the patients
      and the evaluation of the results.

PMID- 21887136
TI  - Contribution of Egr1/zif268 to Activity-Dependent Arc/Arg3.1 Transcription in the
      Dentate Gyrus and Area CA1 of the Hippocampus.
AB  - Egr1, a member of the Egr family of transcription factors, and Arc are immediate
      early genes known to play major roles in synaptic plasticity and memory. Despite
      evidence that Egr family members can control Arc transcriptional regulation,
      demonstration of a selective role of Egr1 alone is lacking. We investigated the
      extent to which activity-dependent Arc expression is dependent on Egr1 by
      analyzing Arc mRNA expression using fluorescence insitu hybridization in the
      dorsal dentate gyrus and CA1 of wild-type (WT) and Egr1 knockout mice. Following
      electroconvulsive shock, we found biphasic expression of Arc in area CA1 in mice,
      consisting in a rapid (30 min) and transient wave followed by a second late-phase
      of expression (8 h), and a single but prolonged wave of expression in the dentate
      gyrus. Egr1 deficiency abolished the latest, but not the early wave of Arc
      expression in CA1, and curtailed that of the dentate gyrus. Since the early wave
      of Arc expression was not affected in Egr1 mutant mice, we next analyzed
      behaviorally induced Arc expression patterns as an index of neural ensemble
      activation in the dentate gyrus and area CA1 of WT and Egr1 mutant mice. Spatial
      exploration of novel or familiar environments induced in mice a single early and
      transient wave of Arc expression in the dentate gyrus and area CA1, which were
      not affected in Egr1 mutant mice. Analyses of Arc-expressing cells revealed that
      exploration recruits similar size dentate gyrus and CA1 neural ensembles in WT
      and Egr1 knockout mice. These findings suggest that hippocampal neural ensembles
      are normally activated immediately following spatial exploration in Egr1 knockout
      mice, indicating normal hippocampal encoding of information. They also provide
      evidence that in condition of strong activation Egr1 alone can control late
      phases of activity-dependent Arc transcription in the dentate gyrus and area CA1
      of the hippocampus.

PMID- 21887137
TI  - The Dopamine and Cannabinoid Interaction in the Modulation of Emotions and
      Cognition: Assessing the Role of Cannabinoid CB1 Receptor in Neurons Expressing
      Dopamine D1 Receptors.
AB  - Although cannabinoid CB1 receptors (CB1Rs) are densely expressed in neurons
      expressing dopamine D1 receptors (D1Rs), it is not fully understood to what
      extent they modulate emotional behaviors. We used conditional CB1R knock-out
      animals lacking CB1Rs in neurons expressing D1R (D1-CB1(-/-)) in order to answer
      this question. To elucidate the behavioral effects of CB1R deficiency in this
      specific neuronal subpopulation, we subjected D1-CB1(-/-) mice to a battery of
      behavioral tests which included exploration-based tests, depressive-like
      behavioral tests, social behavior, and fear-related memory paradigms. D1-CB1(-/-)
      did not show any difference in the exploration-based paradigms such as open
      field, elevated plus maze, or novel object investigation test, except for an
      increase in novelty-induced grooming. By contrast, they showed a mild anhedonia
      like state as described by the slightly decreased preference for sweet solution,
      as compared to wild-type control group. This decrease, however, could be observed
      only during the first day of exposure, thus suggesting increased neophobia as an
      alternative explanation. Accordingly, mutant mice performed normally in the
      forced swim test, a procedure widely used for evaluating behavioral despair in
      rodents. However, weak- to moderate anxiety-like phenotypes were evident when D1
      CB1(-/-) mice were tested for social behavior. Most strikingly, D1-CB1(-/-) mice
      exhibited significantly increased contextual and auditory-cued fear, with
      attenuated within session extinction, suggesting that a specific reduction of
      endocannabinoid signaling in neurons expressing dopamine D1Rs is able to affect
      acute fear adaptation. These results provided first direct evidence for a cross
      talk between dopaminergic D1Rs and endocannabinoid system in terms of controlling
      negative affect.

PMID- 21887138
TI  - Relaxin-3-deficient mice showed slight alteration in anxiety-related behavior.
AB  - Relaxin-3 is a neuropeptide belonging to the relaxin/insulin superfamily. Studies
      using rodents have revealed that relaxin-3 is predominantly expressed in neurons
      in the nucleus incertus (NI) of the pons, the axons of which project to forebrain
      regions including the hypothalamus. There is evidence that relaxin-3 is involved
      in several functions, including food intake and stress responses. In the present
      study, we generated relaxin-3 gene knockout (KO) mice and examined them using a
      range of behavioral tests of sensory/motor functions and emotion-related
      behaviors. The results revealed that relaxin-3 KO mice exhibited normal growth
      and appearance, and were generally indistinguishable from wild genotype
      littermates. There was no difference in bodyweight among genotypes until at least
      28 weeks after birth. In addition, there were no significant differences between
      wild-type and KO mice in locomotor activity, social interaction, hot plate test
      performance, fear conditioning, depression-like behavior, and Y-maze test
      performance. However, in the elevated plus maze test, KO mice exhibited a robust
      increase in the tendency to enter open arms, although they exhibited normal
      performance in a light/dark transition test and showed no difference from wild
      type mice in the time spent in central area in the open field test. On the other
      hand, a significant increase in the acoustic startle response was observed in KO
      mice. These results indicate that relaxin-3 is slightly involved in the anxiety
      related behavior.

PMID- 21887139
TI  - Gone but not Forgotten.

PMID- 21887140
TI  - Functional Brain Network Characterization and Adaptivity during Task Practice in
      Healthy Volunteers and People with Schizophrenia.
AB  - Cognitive remediation involves task practice and may improve deficits in people
      suffering from schizophrenia, but little is known about underlying
      neurophysiological mechanisms. In people with schizophrenia and controls, we used
      magnetoencephalography (MEG) to examine accuracy and practice-related changes in
      parameters indexing neural network structure and activity, to determine whether
      these might be useful assays of the efficacy of cognitive remediation. Two MEG
      recordings were acquired during performance of a tone discrimination task used to
      improve the acuity of auditory processing, before and after ~2.5 h of task
      practice. Accuracy before practice was negatively correlated with beta-band cost
      efficiency, a graph theoretical measure of network organization. Synthetic
      aperture magnetometry was used to localize brain oscillations with high spatial
      accuracy; results demonstrated sound and sensorimotor modulations of the beta
      band in temporo-parietal regions and the sensorimotor cortex respectively. High
      gamma activity also correlated with sensorimotor processing during the task, with
      activation of auditory regions following sound stimulation, and activation of the
      left sensorimotor cortex preceding the button press. High-gamma power in the left
      frontal cortex was also found to correlate with accuracy. Following practice,
      sound-induced broad-band power in the left angular gyri increased. Accuracy
      improved and was found to correlate with increased mutual information (MI)
      between sensors in temporal-parietal regions in the beta band but not global cost
      efficiency. Based on these results, we conclude that hours of task practice can
      induce meso-scale changes such as increased power in relevant brain regions as
      well as changes in MI that correlate with improved accuracy.

PMID- 21887141
TI  - Connecting Art and the Brain: An Artist's Perspective on Visual Indeterminacy.
AB  - In this article I will discuss the intersection between art and neuroscience from
      the perspective of a practicing artist. I have collaborated on several scientific
      studies into the effects of art on the brain and behavior, looking in particular
      at the phenomenon of "visual indeterminacy." This is a perceptual state in which
      subjects fail to recognize objects from visual cues. I will look at the
      background to this phenomenon, and show how various artists have exploited its
      effect through the history of art. My own attempts to create indeterminate images
      will be discussed, including some of the technical problems I faced in trying to
      manipulate the viewer's perceptual state through paintings. Visual indeterminacy
      is not widely studied in neuroscience, although references to it can be found in
      the literature on visual agnosia and object recognition. I will briefly review
      some of this work and show how my attempts to understand the science behind
      visual indeterminacy led me to collaborate with psychophysicists and
      neuroscientists. After reviewing this work, I will discuss the conclusions I have
      drawn from its findings and consider the problem of how best to integrate
      neuroscientific methods with artistic knowledge to create truly interdisciplinary
      approach.

PMID- 21887142
TI  - An LCD Monitor with Sufficiently Precise Timing for Research in Vision.
AB  - Until now, liquid crystal display (LCD) monitors have not been used widely for
      research in vision. Despite their main advantages of continuous illumination and
      low electromagnetic emission, these monitors had problems with timing and
      reliability. Here we report that there is at least one new inexpensive 120 Hz
      model, whose timing and stability is on a par with a benchmark cathode-ray tube
      monitor, or even better. The onset time was stable across repetitions, 95%
      confidence interval (the error) of which was <0.01 ms. Brightness was also
      delivered reliably across repeated presentations (<0.04% error) and across blocks
      with different durations (<3% error). The LCD monitor seems suitable for many
      applications in vision research, including the studies that require combined
      accuracy of timing and intensity of visual stimulation.

PMID- 21887143
TI  - The construction of semantic memory: grammar-based representations learned from
      relational episodic information.
AB  - After acquisition, memories underlie a process of consolidation, making them more
      resistant to interference and brain injury. Memory consolidation involves systems
      level interactions, most importantly between the hippocampus and associated
      structures, which takes part in the initial encoding of memory, and the
      neocortex, which supports long-term storage. This dichotomy parallels the
      contrast between episodic memory (tied to the hippocampal formation), collecting
      an autobiographical stream of experiences, and semantic memory, a repertoire of
      facts and statistical regularities about the world, involving the neocortex at
      large. Experimental evidence points to a gradual transformation of memories,
      following encoding, from an episodic to a semantic character. This may require an
      exchange of information between different memory modules during inactive periods.
      We propose a theory for such interactions and for the formation of semantic
      memory, in which episodic memory is encoded as relational data. Semantic memory
      is modeled as a modified stochastic grammar, which learns to parse episodic
      configurations expressed as an association matrix. The grammar produces tree-like
      representations of episodes, describing the relationships between its main
      constituents at multiple levels of categorization, based on its current knowledge
      of world regularities. These regularities are learned by the grammar from
      episodic memory information, through an expectation-maximization procedure,
      analogous to the inside-outside algorithm for stochastic context-free grammars.
      We propose that a Monte-Carlo sampling version of this algorithm can be mapped on
      the dynamics of "sleep replay" of previously acquired information in the
      hippocampus and neocortex. We propose that the model can reproduce several
      properties of semantic memory such as decontextualization, top-down processing,
      and creation of schemata.

PMID- 21887144
TI  - Is Bile Acid Malabsorption Really a Common Feature of Crohn's Disease or is It
      Simply a Consequence of Ileal Resection?

PMID- 21887145
TI  - Altered social reward and attention in anorexia nervosa.
AB  - Dysfunctional social reward and social attention are present in a variety of
      neuropsychiatric disorders including autism, schizophrenia, and social anxiety.
      Here we show that similar social reward and attention dysfunction are present in
      anorexia nervosa (AN), a disorder defined by avoidance of food and extreme weight
      loss. We measured the implicit reward value of social stimuli for female
      participants with (n = 11) and without (n = 11) AN using an econometric choice
      task and also tracked gaze patterns during free viewing of images of female faces
      and bodies. As predicted, the reward value of viewing bodies varied inversely
      with observed body weight for women with anorexia but not control women, in
      contrast with their explicit ratings of attractiveness. Surprisingly, women with
      AN, unlike control women, did not find female faces rewarding and avoided looking
      at both the face and eyes - independent of observed body weight. These findings
      suggest comorbid dysfunction in the neural circuits mediating gustatory and
      social reward in anorexia nervosa.

PMID- 21887146
TI  - Brain substrates of behavioral programs associated with self-regulation.
AB  - The present paper proposes that four neuromodulator systems underpin highly
      generalized behavioral sets, but each targets either dorsomedial or ventrolateral
      cortical systems, where it produces its effects in either a proactive or reactive
      orientation to the environment. This way systems are discriminated that control
      reactive approach (dopaminergic), reactive avoidance (cholinergic), proactive
      behavior (noradrenergic), and withdrawal (serotonergic). This model is compared
      with models of temperament, affect, personality, and so-called two-system models
      from psychology. Although the present model converges with previous models that
      point to a basic scheme underlying temperamental and affective space, at the same
      time it suggest that specific additional discriminations are necessary to improve
      descriptive fit to data and solve inconsistencies and confusions. We demonstrate
      how proactive and reactive actions and controls can be confused, and that this
      has many potential implications for psychology and neurobiology. We uncover
      conceptual problems regarding constructs such as effortful control, positive
      affect, approach-avoidance, extraversion, impulsivity, impulse-control, and goal
      directedness of behavior. By delineating those problems, our approach also opens
      up ways to tackle them.

PMID- 21887148
TI  - Neural correlates of contents and levels of consciousness.
AB  - Experimental investigations of the neural substrate of consciousness typically
      take one of two paths, studying (1) contents or (2) levels of consciousness. It
      seems obvious to most that these two "paths" are interrelated, yet much less
      obvious how. This paper gives one suggestion to grasp the interrelation, arguing
      that conscious levels are determined by conscious contents in a very specific
      way. It follows from the argument that conscious contents are so-called natural
      kinds, whereas conscious levels are not.

PMID- 21887147
TI  - Separate mechanisms for audio-tactile pitch and loudness interactions.
AB  - A major goal in perceptual neuroscience is to understand how signals from
      different sensory modalities are combined to produce stable and coherent
      representations. We previously investigated interactions between audition and
      touch, motivated by the fact that both modalities are sensitive to environmental
      oscillations. In our earlier study, we characterized the effect of auditory
      distractors on tactile frequency and intensity perception. Here, we describe the
      converse experiments examining the effect of tactile distractors on auditory
      processing. Because the two studies employ the same psychophysical paradigm, we
      combined their results for a comprehensive view of how auditory and tactile
      signals interact and how these interactions depend on the perceptual task.
      Together, our results show that temporal frequency representations are
      perceptually linked regardless of the attended modality. In contrast, audio
      tactile loudness interactions depend on the attended modality: Tactile
      distractors influence judgments of auditory intensity, but judgments of tactile
      intensity are impervious to auditory distraction. Lastly, we show that audio
      tactile loudness interactions depend critically on stimulus timing, while pitch
      interactions do not. These results reveal that auditory and tactile inputs are
      combined differently depending on the perceptual task. That distinct rules govern
      the integration of auditory and tactile signals in pitch and loudness perception
      implies that the two are mediated by separate neural mechanisms. These findings
      underscore the complexity and specificity of multisensory interactions.

PMID- 21887149
TI  - Introduction to the special topic embodied and grounded cognition.

PMID- 21887150
TI  - Age-related changes in electrophysiological and neuropsychological indices of
      working memory, attention control, and cognitive flexibility.
AB  - Older adults exhibit great variability in their cognitive abilities, with some
      maintaining high levels of performance on executive control tasks and others
      showing significant deficits. Previous event-related potential (ERP) work has
      shown that some of these performance differences are correlated with persistence
      of the novelty/frontal P3 in older adults elicited by task-relevant events,
      presumably reflecting variability in the capacity to suppress orienting to
      unexpected but no longer novel events. In recent ERP work in young adults, we
      showed that the operation-span (OSPAN) task (a measure of attention control) is
      predictive of the ability of individuals to keep track of stimulus sequencing and
      to maintain running mental representations of task stimuli, as indexed by the
      parietally distributed P300 (or P3b). Both of these phenomena reflect aspects of
      frontal function (cognitive flexibility and attention control, respectively). To
      investigate these phenomena we sorted both younger and older adults into low- and
      high-working memory spans and low- and high-cognitive flexibility subgroups, and
      examined ERPs during an equal-probability choice reaction time task. For both age
      groups (a) participants with high OSPAN scores were better able to keep track of
      stimulus sequencing, as indicated by their smaller P3b to sequential changes; and
      (b) participants with lower cognitive flexibility had larger P3a than their high
      scoring counterparts. However, these two phenomena did not interact suggesting
      that they manifest dissociable control mechanisms. Further, the fact that both
      effects are already visible in younger adults suggests that at least some of the
      brain mechanisms underlying individual differences in cognitive aging may already
      operate early in life.

PMID- 21887151
TI  - Surface structures involved in plant stomata and leaf colonization by shiga
      toxigenic Escherichia coli o157:h7.
AB  - Shiga-toxigenic Escherichia coli (STEC) O157:H7 uses a myriad of surface adhesive
      appendages including pili, flagella, and the type 3 secretion system (T3SS) to
      adhere to and inflict damage to the human gut mucosa. Consumption of contaminated
      ground beef, milk, juices, water, or leafy greens has been associated with
      outbreaks of diarrheal disease in humans due to STEC. The aim of this study was
      to investigate which of the known STEC O157:H7 adherence factors mediate
      colonization of baby spinach leaves and where the bacteria reside within tainted
      leaves. We found that STEC O157:H7 colonizes baby spinach leaves through the
      coordinated production of curli, the E. coli common pilus, hemorrhagic coli type
      4 pilus, flagella, and T3SS. Electron microscopy analysis of tainted leaves
      revealed STEC bacteria in the internal cavity of the stomata, in intercellular
      spaces, and within vascular tissue (xylem and phloem), where the bacteria were
      protected from the bactericidal effect of gentamicin, sodium hypochlorite or
      ozonated water treatments. We confirmed that the T3S escN mutant showed a reduced
      number of bacteria within the stomata suggesting that T3S is required for the
      successful colonization of leaves. In agreement, non-pathogenic E. coli K-12
      strain DH5alpha transformed with a plasmid carrying the locus of enterocyte
      effacement (LEE) pathogenicity island, harboring the T3SS and effector genes,
      internalized into stomata more efficiently than without the LEE. This study
      highlights a role for pili, flagella, and T3SS in the interaction of STEC with
      spinach leaves. Colonization of plant stomata and internal tissues may constitute
      a strategy by which STEC survives in a nutrient-rich microenvironment protected
      from external foes and may be a potential source for human infection.

PMID- 21887152
TI  - Screening of an E. coli O157:H7 Bacterial Artificial Chromosome Library by
      Comparative Genomic Hybridization to Identify Genomic Regions Contributing to
      Growth in Bovine Gastrointestinal Mucus and Epithelial Cell Colonization.
AB  - Enterohemorrhagic E. coli (EHEC) O157:H7 can cause serious gastrointestinal and
      systemic disease in humans following direct or indirect exposure to ruminant
      feces containing the bacterium. The main colonization site of EHEC O157:H7 in
      cattle is the terminal rectum where the bacteria intimately attach to the
      epithelium and multiply in the intestinal mucus. This study aimed to identify
      genomic regions of EHEC O157:H7 that contribute to colonization and
      multiplication at this site. A bacterial artificial chromosome (BAC) library was
      generated from a derivative of the sequenced E. coli O157:H7 Sakai strain. The
      library contains 1152 clones averaging 150 kbp. To verify the library, clones
      containing a complete locus of enterocyte effacement (LEE) were identified by DNA
      hybridization. In line with a previous report, these did not confer a type III
      secretion (T3S) capacity to the K-12 host strain. However, conjugation of one of
      the BAC clones into a strain containing a partial LEE deletion restored T3S.
      Three hundred eighty-four clones from the library were subjected to two different
      selective screens; one involved three rounds of adherence assays to bovine
      primary rectal epithelial cells while the other competed the clones over three
      rounds of growth in bovine rectal mucus. The input strain DNA was then compared
      with the selected strains using comparative genomic hybridization (CGH) on an E.
      coli microarray. The adherence assay enriched for pO157 DNA indicating the
      importance of this plasmid for colonization of rectal epithelial cells. The mucus
      assay enriched for multiple regions involved in carbohydrate utilization,
      including hexuronate uptake, indicating that these regions provide a competitive
      growth advantage in bovine mucus. This BAC-CGH approach provides a positive
      selection screen that complements negative selection transposon-based screens. As
      demonstrated, this may be of particular use for identifying genes with redundant
      functions such as adhesion and carbon metabolism.

PMID- 21887153
TI  - From wild strain to domesticated strain: the philosophy of microbial diversity in
      foods.

PMID- 21887154
TI  - Central role of dendritic cells in shaping the adaptive immune response during
      respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract
      disease in young children. Premature infants, immunocompromised individuals and
      the elderly exhibit the highest risk for the development of severe RSV-induced
      disease. Murine studies demonstrate that CD8 T cells mediate RSV clearance from
      the lungs. Murine studies also indicate that the host immune response contributes
      to RSV-induced morbidity as T-cell depletion prevents the development of disease
      despite sustained viral replication. Dendritic cells (DCs) play a central role in
      the induction of the RSV-specific adaptive immune response. Following RSV
      infection, lung-resident DCs acquire viral antigens, migrate to the lung-draining
      lymph nodes and initiate the T-cell response. This article focuses on data
      generated from both in vitro DC infection studies and RSV mouse models that
      together have advanced our understanding of how RSV infection modulates DC
      function and the subsequent impact on the adaptive immune response.

PMID- 21887155
TI  - An unusual cause of apareunia.
AB  - A 49-year-old woman with history of rheumatoid arthritis presented with worsening
      pelvic pain. A pelvic computed tomography (CT) scan demonstrated a fracture and a
      lytic expansile lesion within the right superior and inferior pubic rami. The
      diagnosis of "insufficiency fractures secondary to rheumatoid arthritis" was
      established. Six months later, she started describing pain and fullness sensation
      in the vagina which eventually led to a complete apareunia. An x ray confirmed
      healing of the previous fractures, fracture of both left superior and inferior
      pubic rami, and an upwards shift of the right hemi-pelvis. Conservative
      management was chosen. Twelve months later, no improvement occurred and she was
      still apareunic. A "corrective osteotomy surgery" was performed and the displaced
      pubic rami and ischial tuberosities were remodelled bilaterally through a
      vertical incision over each labia majora. These bones were partially excised
      until an adequate vaginal opening was established. Her symptoms have impressively
      resolved with complete reverse of the apareunia.

PMID- 21887156
TI  - Chronic graft-versus-host disease mimicking rapid progressive rheumatoid
      arthritis with atlantoaxial subluxation.
AB  - Chronic graft-versus-host disease (cGVHD) may mimic clinical and serological
      features of various autoimmune diseases. We present a case of a 23-year-old man
      who developed vitiligo, symmetric polyarthritis, high titre rheumatoid factor,
      antinuclear antibodies and anti-double stranded DNA antibodies after allogenic
      peripheral blood stem cell transplantation for severe aplastic anaemia. He was
      treated with low dose oral steroids, non-steroid anti-inflammatory drugs and
      azathioprine and clinical improvement of polyarthritis were observed initially.
      However, atlantoaxial subluxation (C1-C2) and rapid progression of symmetrical
      joint space narrowing in knees and wrists developed within 1 year. cGVHD
      mimicking rheumatoid arthritis with unusual presentations was observed in this
      patient.

PMID- 21887157
TI  - Severe multisystem dysfunction in a case of high level exposure to smoked
      cannabis.
AB  - Cannabis use is common, controversial and its clinical toxicology is likely under
      recognised. A 56-year-old man presented with disabling shortness of breath. He
      smoked up to 7 g cannabis daily for 25 years (maximum 63 875 g) plus large
      amounts of hashish oil. Chest x ray suggested giant bullae. CT of the chest
      revealed over 40 bullae, the largest being 11 cm in diameter. Osteoporosis with
      multiple vertebral crush fractures was noted on plain films and bone densitometry
      (t=-3.19). His dental health was poor. Hypertension, complicated by a large
      occipital stroke was shown by CT of the brain, and increased vascular age (69.8
      years) found by pulse wave analysis. The case is significant as it indicates the
      potential severity of cannabis lung damage and suggests that significant cannabis
      exposure may cause osteoporosis and accelerated vascular ageing. The association
      of alveolar destruction, bone lysis and destruction of arterial elastic laminae
      suggest possible underlying mechanisms such as tissue proteinase activation,
      immunomodulation or stem cell impairment.

PMID- 21887158
TI  - Oesophageal anomaly in a newborn after maternal exposure to mycofenolate mofetil.
AB  - Pregnancy in women with lupus nephritis is associated with increased risk of
      fetal and maternal complications. The risk of poor outcome is higher if there are
      signs of disease activity at conception. The presence of hypertension and anti
      phospholipid antibodies worsens the prognosis. There are very few therapeutic
      options in view of the threat of various congenital anomalies and associated
      comorbidities. Mycofenolate mofetil (MMF) is contraindicated during pregnancy due
      to risk of congenital anomalies and fetal loss. This is a case of a woman with
      membranous lupus nephritis, who went into partial remission with rituximab and
      became pregnant while on maintenance therapy with MMF. Due to lack of alternative
      options, she continued to be given MMF. She had a successful outcome in spite of
      the presence of the poor prognostic factors. The baby had asymptomatic non
      communicating duplication of the oesophagus, which has never been reported before
      in association with MMF during pregnancy.

PMID- 21887159
TI  - Coronary artery dissection in adult-onset homocystinuria.
AB  - The present report concerns the first case of a spontaneous arterial coronary
      dissection in adult onset homocystinuria leading to a premature myocardial
      infarct. The patient had also presented an unexplained lower limb venous
      thrombosis at the age of 41. A carotid artery thrombosis was found at the aged of
      61 during the investigations for facial nerve palsy. The diagnosis of
      homocystinuria was delayed as it was only performed 20 years after the first
      thrombotic event. From observation, a pectus carinatum was the only clinical
      characteristic that could be related to homocystinuria phenotype. Cystathionine
      beta-synthase (CBS) gene analysis showed compound heterozygous mutations. After 3
      months of pyridoxine, the plasma homocysteine level was totally normalised.

PMID- 21887160
TI  - Spontaneous resolution of lung opacities reported as metastases in a patient with
      a history of leiomyosarcoma.
AB  - This is a case of a 69-year-old woman who was diagnosed as having metastatic
      leiomyosarcoma. She presented with multiple lung opacities on plain films and CT
      scans following resection of a high-grade leiomyosarcoma of the uterus 16 months
      earlier. The radiological, oncology, gynaecology and respiratory teams diagnosed
      metastatic cancer on the basis of the clinical presentation and radiological
      appearance. Surprisingly, despite no treatment, there was gradual resolution of
      the lung lesions on plain films. A CT scan 18 months later showed full resolution
      of the lesions. The consultants from the various specialities involved in this
      case were unable to give a satisfactory explanation as to why these lesions
      resolved.

PMID- 21887161
TI  - Catastrophic gastrointestinal bleeding caused by aortoesophageal fistula
      secondary to mycotic thoracic aortic aneurysm.

PMID- 21887163
TI  - Midget submarine for diagnosing midgut lesions in children.
AB  - Anaemia due to obscure gastrointestinal blood loss remains a challenge to the
      clinician, especially when blood loss is severe enough to result in profound
      anaemia while further investigations fail to identify the cause of bleeding. A
      description of how wireless capsule endoscopy revealed a bleeding jejunal
      haemangioma in a 2.5-year-old boy with recurrent anaemia is given. New techniques
      such as wireless capsule endoscopy and double balloon enteroscopy are feasible
      and provide a valuable adjunct to the diagnostic investigation of children with
      obscure enteral blood loss.

PMID- 21887162
TI  - Acute liver injury associated with the use of herbal preparations containing
      glucosamine: three case studies.
AB  - The use of complementary and alternative medicines is becoming increasingly
      popular in Western society. As a result the number of reported adverse reactions
      is increasing. Glucosamine is a herbal remedy commonly used to ease joint pain in
      osteoarthritis, and only two previous reports of hepatotoxicity have been
      published in the scientific literature. The present report describes three
      patients who developed acute liver injury following exposure to glucosamine; one
      patient made a complete recovery on cessation of ingestion, the second developed
      chronic hepatitis and the third died following progression to fulminant hepatic
      failure. A diagnosis of glucosamine-induced hepatotoxicity was made based on the
      temporal relationship between onset of liver injury and glucosamine ingestion,
      exclusion of all other potential aetiologies and, in the two surviving cases,
      improvement in condition on withdrawal of the supplement.

PMID- 21887164
TI  - Vesicoureteric reflux diagnosed by urethral catheterisation.

PMID- 21887165
TI  - Neonatal respiratory distress: do not forget the rarer causes!

PMID- 21887166
TI  - CSF shunt re-infections in children.

PMID- 21887167
TI  - Reducing CSF shunt placement in patients with spinal myelomeningocele.
AB  - OBJECT: The incidence of hydrocephalus requiring shunts in children with
      myelomeningocele (MMC) is reported to be very high. Shunt-related complications
      are a significant cause of morbidity and mortality in this population. In order
      to minimize shunt placements, we used very rigid clinical selection criteria and
      followed them in all patients who had myelomeningocele and enlarged ventricles.
      The follow-up outcome of this retrospective study is reported. METHODS: From 2000
      to 2007, 23 patients with myelomeningocele and variable degree of hydrocephalus
      were treated at our institute with primary surgical closure of their
      myelomeningoceles without a CSF diversion procedure. Patients with severe
      hydrocephalus who required immediate shunt insertion, and those with no
      significant associated hydrocephalus were not included in this study. Data
      regarding the surgical results and complications, postoperative management, and
      the outcome at follow-up were obtained from their hospital records. RESULTS:
      Initially increased size of the ventricular system was found to have decreased or
      stabilized in 17 (81%) patients postoperatively. However, ventriculomegaly
      continued to progress further in 4 (19%) out of 21 patients. Of 11 patients who
      presented with enlarged head, eight (73%) patients showed reduction or
      stabilization in their head circumference. Three (27%) children continued to have
      progressive head enlargement in the postoperative period and required shunt
      placement. Signs of raised intracranial pressure observed in six patients on
      admission, improved in two (33%) and persisted or worsened in four (67%) patients
      who eventually improved after the insertion of a shunt. Eight (35%) patients
      experienced wound-related complications following closure of the MMC, including
      CSF leak in four, wound infection in three, wound breakdown in three, and
      pseudomeningocele in two patients. Shunt placement was required in the
      postoperative period in 13 (56.5%) patients to treat raised intracranial pressure
      in 11 and CSF leak from the wound in two patients. CONCLUSIONS: Our experience
      suggests that the placement of shunts can be reduced by adopting a policy with
      strict clinical and radiographic criteria. Shunt insertion should be reserved for
      only those patients who have severe hydrocephalus with clinical features of
      elevated intracranial pressure. Mild to moderate ventricular dilatation,
      persistent ventriculomagaly, and some increase in ventricular size after
      myelomeningocele repair can be treated successfully without a shunt.

PMID- 21887168
TI  - Choroid plexus papilloma in children: Diagnostic and surgical considerations.
AB  - BACKGROUND: Choroid plexus papilloma (CPP) is a benign neoplasm that arises from
      the ventricular choroid plexus. The clinical features, radiological
      characteristics, and treatment have been discussed in this study for a pediatric
      population. METHODS: Over an eight-year period, seven pediatric (<=12 years) CPP
      patients were treated. Tumors were located in the lateral ventricle (n = 4), IVth
      ventricle (n = 2), and in both the lateral and IIIrd ventricles (n = 1). The
      patients presented predominantly with features of raised intracranial pressure.
      Total microsurgical excision was carried out in all cases. RESULTS: There was
      complete relief of symptoms at follow-up in six patients. A 2.5 year-old child
      with a large trigonal CPP with hydrocephalus leading to complete visual
      impairment, died due to postoperative hypokalemia that caused ventricular
      fibrillation. One of our patients required a postoperative, permanent CSF
      diversion procedure while another required a subduroperitoneal shunt for
      persisting postoperative subdural CSF collection. CONCLUSIONS: Coagulation of the
      tumor under constant irrigation to shrink and excise it in toto, avoids excessive
      bleeding during surgery. The vascular pedicle supplying the tumor should be
      adequately dealt with during the last part of tumor removal as retraction of a
      bleeding pedicle may result in ventricular hemorrhage and brain edema. Following
      surgery, an external ventricular drain for three days helps in preventing the
      development of acute hydrocephalus in lateral ventricular lesions, and the color
      of the drained CSF gives an estimate of the ventricular hemostasis achieved.
      Total excision is usually possible in these cases with excellent postoperative
      outcomes.

PMID- 21887169
TI  - Transcerebellar stereotactic biopsy for brainstem lesions in children.
AB  - Brain stem lesions are pathologically heterogeneous. Pre-operative radiological
      diagnoses prove to be wrong in 10 to 20% of cases. It is therefore imperative to
      have a tissue diagnosis for appropriate therapeutic measures. We report a series
      of 24 patients (14 males, ten females, age range: 6-17 years) CT guided
      stereotactic biopsy for brain stem lesions approached via the suboccipital
      transcerebellar route in semi sitting position with principle used to violate
      only one pial plane with the biopsy probe not entering the ventral surface of the
      cerebellum. The inclusion and exclusion criteria with detailed material and
      method are discussed. Histological diagnosis was established in 23 patients (96%)
      with no procedure-related mortality. Our results indicate that stereotaxic
      approach to brain-stem lesions provides a high yield of positive histological
      diagnoses with a low incidence of morbidity. Awake CT-guided stereotactic biopsy
      via the suboccipital transcerebellar route in a semi-sitting position is a safe,
      reliable, and effective method for brainstem lesions that can obtain adequate
      tissue for histological diagnosis, thus providing each patient with the best
      available treatment.

PMID- 21887171
TI  - Tissue expansion technique for closure of myelomeningocele.

PMID- 21887170
TI  - Central nervous system infection in the pediatric population.
AB  - Infection of the central nervous system is a life-threatening condition in the
      pediatric population. Almost all agents can cause infection within the central
      nervous system and the extent of infection ranges from diffuse involvement of the
      meninges, brain, or the spinal cord to localized involvement presenting as a
      space-occupying lesion. Modern imaging techniques define the anatomic region
      infected, the evolution of the disease, and help in better management of these
      patients. Acute bacterial meningitis remains a major cause of mortality and long
      term neurological disability. Fortunately, the incidence of infection after clean
      craniotomy is < 5%, but it leads to significant morbidity as well as fiscal loss.
      The most significant causative factor in postcraniotomy infections is
      postoperative CSF leak. Cerebral abscess related to organic congenital heart
      disease is one of the leading causes of morbidity and mortality in the pediatric
      population. The administration of prophylactic antibiotics is indicated for
      contaminated and clean-contaminated wounds.

PMID- 21887172
TI  - Olanzapine induced tardive dystonia in case of adolescent bipolar disorder.
AB  - Atypical antipsychotics are increasingly being associated with neurological side
      effects. Risperidone, quetiapine, and aripiprazole have been associated with
      tardive dystonia among other side effects. Similarly, olanzapine has also been
      associated with this troublesome effect. However, these reports are from cases of
      nonaffective psychosis, specially schizophrenia. Moreover, the usual age of onset
      of this neurological side effect has been reported to be in the midthirties or
      later. We present here a case of tardive dystonia associated with the use of
      olanzapine in an adolescent girl suffering from bipolar affective disorder. The
      slight reduction in the severity of the symptoms with the stopping of olanzapine
      and the reemergence of the full-blown symptoms with the reintroduction of
      olanzapine, suggest the contributory role of olanzapine.

PMID- 21887173
TI  - Acute flaccid paralysis due to rabies.
AB  - TWO CLINICAL FORMS OF RABIES ARE RECOGNIZE: i) a furious form associated with
      classical signs of excitation or phobic symptoms, ii) Dumb rabies (paralytic
      rabies) characterized by progressive paralysis without an initial furious phase
      wherein distinction from Guillain-Barre Syndrome may be difficult. Paralytic
      rabies is more common in persons who have received postexposure vaccination. We
      report here the diagnostic dilemma of two cases of acute flaccid paralysis due to
      rabies.

PMID- 21887174
TI  - Recurrent cerebral larva migrans: A case report and review of literature.
AB  - Cerebral larva migrans (CLM) is an uncommon and rarely diagnosed entity. We
      report here a histopathologically proven case of CLM in a 13 year-old girl, who
      presented with bilateral focal seizures, right hemiparesis, and lapsed into
      altered sensorium prior to admission. Her CT scan was suggestive of a
      granulomatous lesion which eventually turned out to be CLM (toxocariasis).
      Interestingly, the lesion recurred after excision, with a confusing clinical
      picture. Following the second surgery, the pathology was reconfirmed and cure was
      provided for the disease. There has been no further intracranial recurrence
      during the past ten years although she developed cutaneous lesions.

PMID- 21887175
TI  - Hydrocephalic holoprosencephaly: An oxymoron? Insights into etiology and
      management.
AB  - Holoprosencephaly is usually associated with microcephaly, although macrocephaly
      is not uncommonly seen. However, the cause of hydrocephalus in holoprosencephaly
      remains ill-defined. Here, the authors report a case of CSF ascites following
      ventriculoperitoneal shunt placement in a five month-old child with alobar
      holoprosencephaly, and hypothesize that the excessive CSF production which occurs
      in this condition may be responsible for the formation of CSF ascites. Further
      research is required to assess whether the gene responsible for holoprosencephaly
      is also responsible for upregulating CSF production in patients with concomitant
      hydrocephalus.

PMID- 21887176
TI  - Respiratory depression during VP shunting in Arnold Chiari malformation Type-II,
      a rare complication (Case reports and review of literature).
AB  - The VP Shunt is a common pediatric surgical procedure in our country.
      Hydrocephalus is commonly associated with meningomyelocele in Arnold Chiari
      malformation-II and the ventriculoperitoneal shunt insertion is the common
      surgical procedure for the management of hydrocephalus. The standard protocol is
      to rule out any hydrocephalus by preoperative MRI. If associated with
      hydrocephalus, insertion of the VP shunt is indicated before the repair of MMC
      whereas the absence of hydrocephalus indicates that the surgical repair of MMC is
      to be undertaken immediately. Anesthetic management of the patient during the
      insertion of ventriculoperitoneal shunt may pose problems. We report here two
      cases of ACM-II (lumbar MMC with associated hydrocephalus) who had respiratory
      depression / delayed emergence after an otherwise uneventful procedure. Although
      the VP shunt (first procedure) required postoperative ventilation which improved
      later, the phenomena of respiratory depression / delayed emergence did not occur
      after the MMC repair (second surgery). The possible mechanisms involved in these
      events and their various clinical aspects are discussed below.

PMID- 21887177
TI  - An adolescent girl with periodic hypersomnolence and megaphagia.

PMID- 21887178
TI  - Primitive neuroectodermal tumor (MB) versus atypical teratoid/rhabdoid tumors, an
      imaging dilemma!

PMID- 21887179
TI  - Septo-optic dysplasia with olfactory tract hypoplasia.

PMID- 21887180
TI  - Hyponatremia in a patient with meningitis and Crohn disease: Cerebral salt
      wasting or SIADH?

PMID- 21887181
TI  - Acquired epileptic aphasia: Landau-Kleffner syndrome.

PMID- 21887182
TI  - Delleman syndrome with Goldenhar overlap.

PMID- 21887183
TI  - Nondysraphic intradural spinal lipoma.

PMID- 21887184
TI  - Meningiomas in children: A study of 18 cases.
AB  - BACKGROUND: Intracranial meningiomas are rare tumors in children accounting for
      0.4-4.6% of all primary brain tumors in the age group of 0-18 years. OBJECTIVE:
      To retrospectively analyze the epidemiological profile, clinical features,
      radiological findings, type of excision, histopathological findings, and overall
      management profile of these patients. MATERIALS AND METHODS: Eighteen consecutive
      cases of meningioma in patients under 18 years of age admitted and operated at
      our institute between the years 1974-2005 were included in this study. RESULTS:
      The mean age of patient at presentation to our hospital was 12.81 years. The male
      to female ratio was 1.57:1. The median preoperative duration of symptoms was 1.2
      years. An increased incidence was seen in patients with neurofibromatosis.
      Intraventricular and skull base locations were common. Total tumor excision was
      achieved in all cases. CONCLUSION: A higher incidence of atypical and aggressive
      meningiomas is seen in children. Children with complete resection and a typical
      benign histology have a good prognosis.

PMID- 21887185
TI  - Outcome of endoscopic third ventriculostomy and Chhabra shunt system in
      noncommunicating non-tumor childhood hydrocephalus.
AB  - BACKGROUND: Endoscopic third ventriculostomy (ETV) the main alternative to
      ventriculoperitoneal shunt (VPS) is just beginning to have a foothold in West
      Africa. It provides a great opportunity for a hydrocephalic child to be shunt
      free. The purpose of this paper is to compare outcome following ETV and VPS
      (using the cheap Chhabra shunt) in children with noncommunicating non-tumoral
      hydrocephalus in an environment where late presentation is the norm. MATERIALS
      AND METHODS: Sixty-three pediatric patients (< 6 years) with hydrocephalus who
      underwent a VPS or ETV at our hospital were included in this study. The study
      period was of 30 months (January 2006 till June 2008). Clinically successful
      outcome was defined as no event occurring during or after surgery that resulted
      in an alternate surgical procedure, or significant post-operative complication
      that includes death. All complications related to the procedures were also
      analyzed. RESULTS: The outcome of surgical intervention was not significantly
      related to the gender, age of the patient at surgery, or type of surgery. The
      post-operative complication rate was similar in both groups. CONCLUSIONS: The
      clinical outcome of ETV is comparable to that of VPS, with the added benefit of
      no shunt-related problems; and being a short procedure, patient anesthesia and
      operation time, hospital stay, and cost are significantly reduced. We consider
      ETV to be the procedure of choice for the treatment of noncommunicating
      nontumoral hydrocephalus in the pediatric population.

PMID- 21887186
TI  - Effect of detethering on bladder function in children with myelomeningocele:
      Urodynamic evaluation.
AB  - AIM OF WORK: To study the effect of detethering of the cord on urodynamic changes
      in patients with myelomeningocele. MATERIALS AND METHODS: We retrospectively
      reviewed the urodynamic data of 37 patients. In all of them myelomeningocele
      primary repair was carried out. The patients were divided into two groups: (1)
      those who underwent detethering of the cord and (2) those who did not.
      Neurourological examination, filling cystometry, assessment of bladder
      management, and fecal continence were studied in all patients. RESULTS: Eleven
      (29.7%) out of 37 patients underwent detethering of the cord. The mean age at
      presentation was 10.1 +/- 4 and 10.8 +/- 7 years in groups 1 and 2, respectively
      (P 0.7). Nocturnal and diurnal enuresis was found in 45% of group 1, while it was
      found in 69% of group 2. Fecal soiling was detected in 18% in group 1 and in
      38.5% in group 2. Mean bladder capacity was 210 +/- 125 cc and 199 +/- 120 cc for
      groups 1 and 2, respectively (P 0.8). Uninhibited detrusor contractions were
      noticed in nine patients (82%) of group 1 and in 21 patients (81%) of group 2.
      Delta det LPP was lower in group 1 (35 +/- 19 cm H(2)O) than in group 2 (46 +/-
      40 cm H(2)0). CONCLUSION: Detethering of the cord had a positive impact on
      patients with myelomeningocele in terms of lowering of det LPP and accordingly
      decreasing the risk of upper tract deterioration.

PMID- 21887187
TI  - Candidal infections of ventriculoperitoneal shunts.
AB  - Although ventriculoperitoneal (VP) shunt infection is a common complication of
      shunt procedures, fungal infection is considered to be rare. In the present
      study, we performed retrospective analysis of six cases in which candida
      infection occurred. In all these six cases, VP shunt was performed in children
      for hydrocephalus and the onset of symptoms varied between seven days to one
      month after the surgical procedure was performed. The commonest clinical signs
      and symptoms were fever (100%), vomiting (100%), and altered sensorium (50%). The
      commonest isolate was Candida albicans (66.66%) followed by Candida parapsilosis
      and Candida glabrata in one case each. All the patients were successfully treated
      with Amphotericin B and there was no mortality recorded.

PMID- 21887188
TI  - Adhesion molecule levels in serum and cerebrospinal fluid in children with
      bacterial meningitis and sepsis.
AB  - BACKGROUND: Adhesion molecules play a role in leukocyte recruitment during
      central nervous system (CNS) inflammation. AIM: This study was designed to
      compare serum, cerebrospinal fluid (CSF) concentrations of adhesion molecules in
      children with meningitis and sepsis, and to evaluate their sources. SETTING: This
      study was carried out at Pediatric Department, King Abdulaziz University Hospital
      from January 2007 to June 2008. DESIGN: Serum and CSF samples were collected on
      admission from meningitis (n = 40), sepsis (n = 20) patients, and sera from
      controls (n = 20). MATERIALS AND METHODS: Endothelial (E), leukocyte (L),
      platelet (P) selectins intercellular cell adhesion molecule-1 (ICAM-1), and
      vascular cell adhesion molecules-1 (VCAM-1) were measured using ELISA.
      STATISTICS: ANOVA and Spearman's correlations were used. Adhesion molecules with
      albumin concentration were estimated in CSF/serum to calculate concentration
      quotients. RESULTS: In meningitis, serum sE-, sL-, sP-selectins sICAM-1, sVCAM-1
      levels were higher than controls. Compared to sepsis, serum sE-selectin, sL
      selectin, sVCAM-1, CSF-sL-selectin, CSF-sVCAM-1, VCAM-1 ratio and index were
      higher, while serum sP-selectin was lower than meningitis. sE-selectin ratio, CSF
      sICAM-1 were higher in meningitis with positive than negative culture. The sE
      selectin index was higher in meningitis with neurological complication than those
      without it. In meningitis, correlation was found between CSF protein and CSF
      white blood cell counts (WBCs), CSF sICAM-1, CSF sVCAM-1 and between CSF sE
      selectin and CSF sICAM-1. CONCLUSIONS: This study supports the role of adhesion
      molecules especially sL-selectin, sVCAM-1 in meningitis and suggests further
      research to determine their use as biomarkers for meningitis and use of their
      antagonists as therapeutic for CNS inflammation. The presence of discrepancy of
      CSF/serum ratios for molecules of same molecular weight suggest intrathecal
      shedding in addition to diffusion through the blood-CSF barrier.

PMID- 21887189
TI  - Pediatric craniofacial surgery for craniosynostosis: Our experience and current
      concepts: Part -1.
AB  - Craniostenosis is a disease characterized by untimely fusion of cranial sutures
      resulting in a variety of craniofacial deformities and neurological sequelae due
      to alteration in cranial volume and restriction of brain growth. This involves
      vault sutures predominantly, but cranial base is not immune. Association with a
      variety of syndromes makes the management decision complex. These children need
      careful evaluation by multiple specialists to have strategic treatment options.
      Parental counseling is an important and integral part of the treatment. Recent
      advancements in the surgical techniques and concept of team approach have
      significantly enhanced the safety and outcome of these children. We had an
      opportunity of treating 57 children with craniostenosis in the last 15 years at
      our craniofacial service. Out of them, 40 were nonsyndromic and 17 were syndromic
      variety. We describe our successful results along with individualized operative
      technical modifications adopted based on the current understanding of the
      disease.

PMID- 21887190
TI  - Pediatric craniofacial surgery for craniosynostosis: Our experience and current
      concepts: Parts -2.
AB  - Craniostenosis associated with other syndromes poses several clinical and
      management challenges. Involvement of cranial, facial, and systemic defects with
      an underlying genetic abnormality needs comprehensive understanding, to plan
      appropriate and safe treatment modalities. Often, these children require staging
      involving several/multiple surgical procedures. Unsuccessful outcomes and
      retrusion of the deformities are common in comparison to the nonsyndromic
      variety. We present our experience in treating 17 children with syndromic
      craniostenosis with successful outcomes and minimal morbidity. We also describe
      the principles behind the staging. Technology adoption has improved the results
      as well as reduced the complications to an acceptable minimum.

PMID- 21887191
TI  - Endoscopic third ventriculostomy.

PMID- 21887192
TI  - Role of biplane digital subtraction angiography, and 3D rotational angiography in
      craniopagus twins: A case report, detailed pictorial evaluation, and review of
      literature.
AB  - Cranially conjoined twins (craniopagus) are regarded as one of the rarest human
      malformations. Craniopagus represents 2 to 6% of conjoined twins and is the
      rarest type of disorder. A conventional angiogram with three dimensions is needed
      to confirm the exact extent of sharing of the arterial / venous tree. 3D
      angiography was first proposed by CORNELIUS and advanced into clinical practice
      by VOIGT in 1975. We present a case of craniopagus vertical type II twins,
      evaluated for cerebral circulation.

PMID- 21887193
TI  - Changes in the globus pallidus in chronic kernicterus.
AB  - The objective of the study was to establish the diagnosis of kernicterus as a
      cause of seizures and abnormal movements in a 1-year-old child. We performed an
      MRI of the brain of the child on our 1.5 T scanner. The MRI of the patient showed
      high signals on T2-weighted images in the globus pallidus bilaterally, with no
      evidence of mass effect. Because of an increased risk of hearing loss, the brain
      stem evoked response examination was also performed. The brain-stem evoked
      response examination showed bilateral severe sensorineural hearing loss. The
      presence of isolated hyperintense signals in basal ganglia (globus pallidi) was
      very useful in the evaluation of the structural changes in posticteric bilirubin
      encephalopathy.

PMID- 21887194
TI  - Magnetic resonance imaging of bilateral mesial temporal sclerosis in chronic
      kernicterus.
AB  - Kernicterus is an encephalopathy resulting from the cerebral deposition of
      unconjugated bilirubin in the neonatal period. We report a case of kernicterus
      where MRI demonstrated bilateral symmetric high signal intensity and volume loss
      in the hippocampus in addition to globus pallidus and subthalamic nucleus
      hyperintensity onT2-weighted images. The authors believe that hippocampal
      sclerosis, plays a role in adding specificity to the imaging diagnosis of
      kernicterus.

PMID- 21887195
TI  - Unusual complication of ventriculoperitoneal shunt surgery.
AB  - Ventricular shunts are commonly employed in the management of hydrocephalus, and
      numerous complications such as dissection or migration have been reported in the
      literature besides shunt malfunction. We present a case of the migration of the
      peritoneal catheter into the scrotum who attended at our institute. He was
      managed successfully, but subsequently developed intraabdominal cystic swelling
      for which he was reoperated.

PMID- 21887196
TI  - Anal extrusion of a ventriculo peritoneal shunt tube: Endoscopic removal.
AB  - We describe the extrusion of a ventriculo peritoneal shunt tube from the anus
      into a 6-year-old boy following the placement of a ventriculo peritoneal shunt
      for postoperative periventricular tumor-induced hydrocephalus. He was admitted
      with a complaint of extrusion of a tube through anus on and off during bowel
      evacuation. He was evaluated with an X-ray of the abdomen which was showing a
      coiled tube in descending and sigmoid colon, confirmed by sigmoidoscopy. The
      proximal end was exposed for external ventricular drainage and distal end was
      removed endoscopically. The patient was watched for peritonitis and managed
      conservatively. The proximal end of the tube was removed after 5 days of external
      ventricular drainage and after ruling out ventriculitis and meningitis. Bowel
      perforation by a ventriculo peritoneal tube is a rare complication. Diagnosis is
      often difficult and delayed. Most of the bowel perforation is seen in young
      patients.

PMID- 21887197
TI  - Gluteal pseudophallus in a male child: A rare cutaneous marker of occult spinal
      dysraphism.
AB  - Congenital midline paraspinal cutaneous markers have been practically linked to
      the location and nature of neural-tissue lesions. One of the most interesting
      congenital midline paraspinal cutaneous markers has been the human tail in the
      lumbosacral region, with underlying spinal dysraphism. Human tails have many
      shapes and sizes and are usually localized to the lumbosacral region. After a
      complete neurological examination, the MRI is the most sensitive diagnostic
      modality to reveal the underlying occult spinal dysraphic state. Surgical
      excision is aimed at untethering of the spinal cord in symptomatic children and
      for aesthetic reasons in asymptomatic patients. Here we report an asymptomatic
      male child with normal external genitilia, whose tail is attached to the gluteal
      region like an adult phallus and investigations revealed an underlying spinal
      dysraphic state.

PMID- 21887198
TI  - Dandy-Walker variant associated with bipolar affective disorder.
AB  - The Dandy-Walker malformation is a congenital brain malformation, typically
      involving the fourth ventricle and the cerebellum. To date, the Dandy-Walker
      syndrome has not been described in association with bipolar disorder type I
      mania, and therefore we briefly report the case of a Dandy-Walker variant
      associated with acute mania. A 10-year-old boy was brought by his mother to the
      outpatient clinic of the Department of Psychiatry of a tertiary care hospital,
      with symptoms of mania. The MRI brain of the patient showed a posterior fossa
      cystic lesion, a giant cisterna magna communicating with the fourth ventricle and
      mild hypoplasia of the cerebellar vermis, with the rest of the structures being
      normal and no signs of hydrocephalus. These findings showed that the patient had
      a Dandy-Walker variant. He responded partially to valproate and olanzepine, which
      controlled the acute manic symptoms in the ward.

PMID- 21887199
TI  - Therapeutic paradox in CNS tuberculosis.

PMID- 21887200
TI  - Exencephaly in a live, full term fetus.

PMID- 21887201
TI  - Congenital cystic eye with meningocele.

PMID- 21887202
TI  - Kawasaki disease presenting atypically as meningoencephlitis.

PMID- 21887203
TI  - Infantile nonconvulsive status epilepticus caused by herpes encephalitis.

PMID- 21887204
TI  - Acute encephalopathy associated rotavirus gastroenteritis.

PMID- 21887205
TI  - Glutaric aciduria type1: CT diagnosis.

PMID- 21887207
TI  - Viral life cycles captured in three-dimensions with electron microscopy
      tomography.
AB  - Viruses hijack host cell functions and optimize them for viral replication
      causing a severe threat to human health. However, viruses are also tools to
      understand cell biology and they may be effective reagents in nano-medicine.
      Studies from the molecular to cellular levels are aimed at understanding the
      details of viral life cycles and the underlying virus-host interactions. Recent
      developments in electron microscopy tomography allow viral and cellular events to
      be observed in fine structural detail in three-dimension. By combining high
      resolution structures of individual proteins and macro-complexes obtained by
      crystallography and electron cryo-microscopy and image reconstruction with
      reconstructions performed on sub-tomographic volumes, electron tomography has
      advanced the structural and mechanistic understanding of virus infections both in
      vitro and in host cells.

PMID- 21887206
TI  - Statistical Optimization of Pharmacogenomics Association Studies: Key
      Considerations from Study Design to Analysis.
AB  - Research in human genetics and genetic epidemiology has grown significantly over
      the previous decade, particularly in the field of pharmacogenomics.
      Pharmacogenomics presents an opportunity for rapid translation of associated
      genetic polymorphisms into diagnostic measures or tests to guide therapy as part
      of a move towards personalized medicine. Expansion in genotyping technology has
      cleared the way for widespread use of whole-genome genotyping in the effort to
      identify novel biology and new genetic markers associated with pharmacokinetic
      and pharmacodynamic endpoints. With new technology and methodology regularly
      becoming available for use in genetic studies, a discussion on the application of
      such tools becomes necessary. In particular, quality control criteria have
      evolved with the use of GWAS as we have come to understand potential systematic
      errors which can be introduced into the data during genotyping. There have been
      several replicated pharmacogenomic associations, some of which have moved to the
      clinic to enact change in treatment decisions. These examples of translation
      illustrate the strength of evidence necessary to successfully and effectively
      translate a genetic discovery. In this review, the design of pharmacogenomic
      association studies is examined with the goal of optimizing the impact and
      utility of this research. Issues of ascertainment, genotyping, quality control,
      analysis and interpretation are considered.

PMID- 21887208
TI  - Structural studies on antibody recognition and neutralization of viruses.
AB  - The purpose of this brief review is to highlight how structural information can
      elucidate antibody recognition and neutralization of viruses. Studies on human
      rhinovirus demonstrated that antibodies need not induce conformational changes
      for neutralization and that viruses do not conceal receptor-binding regions from
      immune recognition. Ross River and Sindbis virus complexes were an early example
      of using antibodies to demark receptor-binding regions. The structure of an
      antibody bound to mouse norovirus is an example of antibodies binding to sharp
      protrusions on flexible receptor-binding domains. Finally, the structure of
      cucumber mosaic virus bound to a loop involved in aphid transmission demonstrated
      the importance of the context of antigen presentation and what happens when an
      antibody binds near an icosahedral symmetry axis.

PMID- 21887213
TI  - The D153del mutation in GNB3 gene causes tissue specific signalling patterns and
      an abnormal renal morphology in Rge chickens.
AB  - BACKGROUND: The GNB3 gene is expressed in cone but not rod photoreceptors of
      vertebrates, where it acts as the beta transducin subunit in the colour visual
      transduction process. A naturally occurring mutation 'D153del' in the GNB3 gene
      causes the recessively inherited blinding phenotype retinopathy globe enlarged
      (rge) disease in chickens. GNB3 is however also expressed in most other
      vertebrate tissues suggesting that the D153del mutation may exert pathological
      effects that outlie from eye. PRINCIPAL FINDINGS: Recombinant studies in COS-7
      cells that were transfected with normal and mutant recombinant GNB3 constructs
      and subjected to cycloheximide chase showed that the mutant GNB3d protein had a
      much shorter half life compared to normal GNB3. GNB3 codes for the Gbeta3 protein
      subunit that, together with different Ggamma and Galpha subunits, activates and
      regulates phosphorylation cascades in different tissues. As expected, the
      relative levels of cGMP and cAMP secondary messengers and their activated kinases
      such as MAPK, AKT and GRK2 were also found to be altered significantly in a
      tissue specific manner in rge chickens. Histochemical analysis on kidney tissue
      sections, from rge homozygous affected chickens, showed the chickens had
      enlargement of the glomerular capsule, causing glomerulomegaly and
      tubulointerstitial inflammation whereas other tissues (brain, heart, liver,
      pancreas) were unaffected. SIGNIFICANCE: These findings confirm that the D153del
      mutation in GNB3 gene targets GNB3 protein to early degradation. Lack of GNB3
      signalling causes reduced phosphorylation activity of ERK2 and AKT leading to
      severe pathological phenotypes such as blindness and renal abnormalities in rge
      chickens.

PMID- 21887214
TI  - A pilot randomised trial of induced blood-stage Plasmodium falciparum infections
      in healthy volunteers for testing efficacy of new antimalarial drugs.
AB  - BACKGROUND: Critical to the development of new drugs for treatment of malaria is
      the capacity to safely evaluate their activity in human subjects. The approach
      that has been most commonly used is testing in subjects with natural malaria
      infection, a methodology that may expose symptomatic subjects to the risk of
      ineffective treatment. Here we describe the development and pilot testing of a
      system to undertake experimental infection using blood stage Plasmodium
      falciparum parasites (BSP). The objectives of the study were to assess the
      feasibility and safety of induced BSP infection as a method for assessment of
      efficacy of new drug candidates for the treatment of P. falciparum infection.
      METHODS AND FINDINGS: A prospective, unblinded, Phase IIa trial was undertaken in
      19 healthy, malaria-naive, male adult volunteers who were infected with BSP and
      followed with careful clinical and laboratory observation, including a sensitive,
      quantitative malaria PCR assay. Volunteers were randomly allocated to treatment
      with either of two licensed antimalarial drug combinations, artemether
      lumefantrine (A/L) or atovaquone-proguanil (A/P). In the first cohort (n = 6)
      where volunteers received ~360 BSP, none reached the target parasitemia of 1,000
      before the day designated for antimalarial treatment (day 6). In the second and
      third cohorts, 13 volunteers received 1,800 BSP, with all reaching the target
      parasitemia before receiving treatment (A/L, n = 6; A/P, n = 7) The study
      demonstrated safety in the 19 volunteers tested, and a significant difference in
      the clearance kinetics of parasitemia between the drugs in the 13 evaluable
      subjects, with mean parasite reduction ratios of 759 for A/L and 17 for A/P (95%
      CI 120-4786 and 7-40 respectively; p<0.01). CONCLUSIONS: This system offers a
      flexible and safe approach to testing the in vivo activity of novel
      antimalarials. TRIAL REGISTRATION: ClinicalTrials.gov NCT01055002.

PMID- 21887215
TI  - Effect of food residues on norovirus survival on stainless steel surfaces.
AB  - BACKGROUND: In households and food processing plants, minute food residues left
      behind from improper cleaning may influence the survivability of human norovirus
      on surfaces. In this study, the survivability of norovirus on desiccated food
      residue-attached stainless steel coupons was investigated. METHODOLOGY/PRINCIPAL
      FINDINGS: Using murine norovirus-1 (MNV-1) as a surrogate of human norovirus, the
      survivability of norovirus was investigated on lettuce, cabbage, or ground pork
      attached stainless steel coupons. A 6.2 log MPN/ml of MNV-1 infectivity was
      completely lost at day 30 in residue-free coupons, whereas only a 1.4 log MPN/ml
      reduction was observed in coupons with residues. Moreover, the disinfective
      effect of sodium hypochlorite was reduced when residues were present on the
      coupons. CONCLUSIONS/SIGNIFICANCE: This study revealed that the food residues
      increased the survivability and the resistance to chemicals of norovirus,
      indicating the need of thorough cleaning in food processing plants and household
      settings.

PMID- 21887216
TI  - Sentinel surveillance of influenza-like-illness in two cities of the tropical
      country of Ecuador: 2006-2010.
AB  - BACKGROUND: Tropical countries are thought to play an important role in the
      global behavior of respiratory infections such as influenza. The tropical country
      of Ecuador has almost no documentation of the causes of acute respiratory
      infections. The objectives of this study were to identify the viral agents
      associated with influenza like illness (ILI) in Ecuador, describe what strains of
      influenza were circulating in the region along with their epidemiologic
      characteristics, and perform molecular characterization of those strains.
      METHODOLOGY/FINDINGS: This is a prospective surveillance study of the causes of
      ILI based on viral culture of oropharyngeal specimens and case report forms
      obtained in hospitals from two cities of Ecuador over 4 years. Out of 1,702 cases
      of ILI, nine viral agents were detected in 597 patients. During the time of the
      study, seven genetic variants of influenza circulated in Ecuador, causing six
      periods of increased activity. There appeared to be more heterogeneity in the
      cause of ILI in the tropical city of Guayaquil when compared with the Andean city
      of Quito. CONCLUSIONS/SIGNIFICANCE: This was the most extensive documentation of
      the viral causes of ILI in Ecuador to date. Influenza was a common cause of ILI
      in Ecuador, causing more than one outbreak per year. There was no well defined
      influenza season although there were periods of time when no influenza was
      detected alternating with epidemics of different variant strains.

PMID- 21887217
TI  - Sodium coupled bicarbonate influx regulates intracellular and apical pH in
      cultured rat caput epididymal epithelium.
AB  - BACKGROUND: The epithelium lining the epididymis provides an optimal acidic fluid
      microenvironment in the epididymal tract that enable spermatozoa to complete the
      maturation process. The present study aims to investigate the functional role of
      Na(+)/HCO(3)(-) cotransporter in the pH regulation in rat epididymis.
      METHOD/PRINCIPAL FINDINGS: Immunofluorescence staining of pan cytokeratin in the
      primary culture of rat caput epididymal epithelium showed that the system was a
      suitable model for investigating the function of epididymal epithelium.
      Intracellular and apical pH were measured using the fluorescent pH sensitive
      probe carboxy-seminaphthorhodafluor-4F acetoxymethyl ester (SNARF-4F) and
      sparklet pH electrode respectively to explore the functional role of rat
      epididymal epithelium. In the HEPES buffered Krebs-Henseleit (KH) solution, the
      intracellular pH (pHi) recovery from NH(4)Cl induced acidification in the
      cultured caput epididymal epithelium was completely inhibited by amiloride, the
      inhibitor of Na(+)/H(+) exchanger (NHE). Immediately changing of the KH solution
      from HEPES buffered to HCO(3)(-) buffered would cause another pHi recovery. The
      pHi recovery in HCO(3)(-) buffered KH solution was inhibited by 4,
      4diisothiocyanatostilbene-2,2-disulfonic acid (DIDS), the inhibitor of HCO(3)(-)
      transporter or by removal of extracellular Na(+). The extracellular pH
      measurement showed that the apical pH would increase when adding DIDS to the
      apical side of epididymal epithelial monolayer, however adding DIDS to the
      basolateral side had no effect on apical pH. CONCLUSIONS: The present study shows
      that sodium coupled bicarbonate influx regulates intracellular and apical pH in
      cultured caput epididymal epithelium.

PMID- 21887218
TI  - Anti-TNF-alpha therapy enhances the effects of enzyme replacement therapy in rats
      with mucopolysaccharidosis type VI.
AB  - BACKGROUND: Although enzyme replacement therapy (ERT) is available for several
      lysosomal storage disorders, the benefit of this treatment to the skeletal system
      is very limited. Our previous work has shown the importance of the Toll-like
      receptor 4/TNF-alpha inflammatory pathway in the skeletal pathology of the
      mucopolysaccharidoses (MPS), and we therefore undertook a study to examine the
      additive benefit of combining anti-TNF-alpha therapy with ERT in a rat model of
      MPS type VI. METHODOLOGY/PRINCIPAL FINDINGS: MPS VI rats were treated for 8
      months with Naglazyme(r) (recombinant human N-acetyl-galactosamine-4-sulfatase),
      or by a combined protocol using Naglazyme(r) and the rat-specific anti-TNF-alpha
      drug, CNTO1081. Both protocols led to markedly reduced serum levels of TNF-alpha
      and RANKL, although only the combined treatment reduced TNF-alpha in the
      articular cartilage. Analysis of cultured articular chondrocytes showed that the
      combination therapy also restored collagen IIA1 expression, and reduced
      expression of the apoptotic marker, PARP. Motor activity and mobility were
      improved by ERT, and these were significantly enhanced by combination treatment.
      Tracheal deformities in the MPS VI animals were only improved by combination
      therapy, and there was a modest improvement in bone length. Ceramide levels in
      the trachea also were markedly reduced. MicroCT analysis did not demonstrate any
      significant positive effects on bone microarchitecture from either treatment, nor
      was there histological improvement in the bone growth plates.
      CONCLUSIONS/SIGNIFICANCE: The results demonstrate that combining ERT with anti
      TNF-alpha therapy improved the treatment outcome and led to significant clinical
      benefit. They also further validate the usefulness of TNF-alpha, RANKL and other
      inflammatory molecules as biomarkers for the MPS disorders. Further evaluation of
      this combination approach in other MPS animal models and patients is warranted.

PMID- 21887219
TI  - Rec-DCM-Eigen: reconstructing a less parsimonious but more accurate tree in
      shorter time.
AB  - Maximum parsimony (MP) methods aim to reconstruct the phylogeny of extant species
      by finding the most parsimonious evolutionary scenario using the species' genome
      data. MP methods are considered to be accurate, but they are also computationally
      expensive especially for a large number of species. Several disk-covering methods
      (DCMs), which decompose the input species to multiple overlapping subgroups (or
      disks), have been proposed to solve the problem in a divide-and-conquer way. We
      design a new DCM based on the spectral method and also develop the COGNAC
      (Comparing Orders of Genes using Novel Algorithms and high-performance Computers)
      software package. COGNAC uses the new DCM to reduce the phylogenetic tree search
      space and selects an output tree from the reduced search space based on the MP
      principle. We test the new DCM using gene order data and inversion distance. The
      new DCM not only reduces the number of candidate tree topologies but also
      excludes erroneous tree topologies which can be selected by original MP methods.
      Initial labeling of internal genomes affects the accuracy of MP methods using
      gene order data, and the new DCM enables more accurate initial labeling as well.
      COGNAC demonstrates superior accuracy as a consequence. We compare COGNAC with
      FastME and the combination of the state of the art DCM (Rec-I-DCM3) and GRAPPA.
      COGNAC clearly outperforms FastME in accuracy. COGNAC--using the new DCM--also
      reconstructs a much more accurate tree in significantly shorter time than GRAPPA
      with Rec-I-DCM3.

PMID- 21887221
TI  - The immuno-dynamics of conflict intervention in social systems.
AB  - We present statistical evidence and dynamical models for the management of
      conflict and a division of labor (task specialization) in a primate society. Two
      broad intervention strategy classes are observed--a dyadic strategy--pacifying
      interventions, and a triadic strategy--policing interventions. These strategies,
      their respective degrees of specialization, and their consequences for conflict
      dynamics can be captured through empirically-grounded mathematical models
      inspired by immuno-dynamics. The spread of aggression, analogous to the
      proliferation of pathogens, is an epidemiological problem. We show analytically
      and computationally that policing is an efficient strategy as it requires only a
      small proportion of a population to police to reduce conflict contagion.
      Policing, but not pacifying, is capable of effectively eliminating conflict.
      These results suggest that despite implementation differences there might be
      universal features of conflict management mechanisms for reducing contagion-like
      dynamics that apply across biological and social levels. Our analyses further
      suggest that it can be profitable to conceive of conflict management strategies
      at the behavioral level as mechanisms of social immunity.

PMID- 21887220
TI  - Cyclophilin E functions as a negative regulator to influenza virus replication by
      impairing the formation of the viral ribonucleoprotein complex.
AB  - BACKGROUND: The nucleoprotein (NP) of influenza A virus is a multifunctional
      protein that plays a critical role in the replication and transcription of the
      viral genome. Therefore, examining host factors that interact with NP may shed
      light on the mechanism of host restriction barriers and the tissue tropism of
      influenza A virus. Here, Cyclophilin E (CypE), a member of the peptidyl-propyl
      cis-trans isomerase (PPIase) family, was found to bind to NP and inhibit viral
      replication and transcription. METHODOLOGY/PRINCIPAL FINDINGS: In the present
      study, CypE was found to interact with NP but not with the other components of
      the viral ribonucleoprotein complex (VRNP): PB1, PB2, and PA. Mutagenesis data
      revealed that the CypE domain comprised of residues 137-186 is responsible for
      its binding to NP. Functional analysis results indicated that CypE is a negative
      regulator in the influenza virus life cycle. Furthermore, knock-down of CypE
      resulted in increased levels of three types of viral RNA, suggesting that CypE
      negatively affects viral replication and transcription. Moreover, up-regulation
      of CypE inhibited the activity of influenza viral polymerase. We determined that
      the molecular mechanism by which CypE negatively regulates influenza virus
      replication and transcription is by interfering with NP self-association and the
      NP-PB1 and NP-PB2 interactions. CONCLUSIONS/SIGNIFICANCE: CypE is a host
      restriction factor that inhibits the functions of NP, as well as viral
      replication and transcription, by impairing the formation of the vRNP. The data
      presented here will help us to better understand the molecular mechanisms of host
      restriction barriers, host adaptation, and tissue tropism of influenza A virus.

PMID- 21887222
TI  - Modulation of hydrogen peroxide production in cellular systems by low level
      magnetic fields.
AB  - Increased generation of reactive oxygen species (ROS) and an altered redox status
      have long been observed in cancer cells, suggesting that ROS might be involved in
      the development of these cells. However, recent studies suggest that inducing an
      excess of ROS in cancer cells can be exploited for therapeutic benefits. Cancer
      cells in advanced stage tumors frequently exhibit multiple genetic alterations
      and high oxidative stress, suggesting that it might be possible to preferentially
      modulate the development of these cells by controlling their ROS production. Low
      levels of ROS are also important for the development and survival of normal
      cells. In this manuscript, we present data on the influence of the suppression of
      the Earth's magnetic field (low level magnetic fields or LLF) which magnitudes
      range from 0.2 uT to 2 uT on the modulation of hydrogen peroxide (H(2)O(2)) in
      human fibrosarcoma cancer cell line HT1080, pancreatic AsPC-1 cancer cell line,
      and bovine pulmonary artery endothelial cells (PAEC) exposed to geomagnetic field
      (control; 45 uT-60 uT). Reduction of the Earth's magnetic field suppressed
      H(2)O(2) production in cancer cells and PAEC. The addition of catalase and
      superoxide dismutase (SOD) mimetic MnTBAP inhibited the magnetic field effect.
      Modulating ROS production by magnetic fields may open new venues of biomedical
      research and therapeutic strategies.

PMID- 21887223
TI  - Lymphocyte cell-cycle inhibition by HLA-G is mediated by phosphatase SHP-2 and
      acts on the mTOR pathway.
AB  - Human leukocyte antigen G (HLA-G) is involved in regulating T-cell responses
      through its interaction with inhibitory receptors belonging to the immunoglobulin
      like transcript family (ILT). In this context, we investigated the pathways
      involved in the control of cell-cycle entry of T cells following HLA-G
      interaction with its inhibitory receptor. We show that HLA-G acts through its
      interaction with the LILRB1 receptor expressed on T lymphocytes. Both HLA-G and
      LILRB1 antibodies block the inhibitory effect of HLA-G and restore T-cell
      proliferation. The interaction of HLA-G with T lymphocytes is associated with
      phosphorylation of SHP-2 phosphatase, but not SHP-1. In addition, in activated T
      cells, their incubation with HLA-G is not associated with a decrease in the TCR
      or CD28 downstream pathways, but is associated with dephosphorylation of the mTOR
      molecule and p70S6K. In contrast, Akt, which acts upstream of mTOR, is not
      affected by HLA-G. The inhibition of SHP-2 by NSC-87877(5 uM), a chemical
      inhibitor of SHP-2, or the use of siRNA, abrogates dephosphorylation of mTOR and
      impairs the overexpression of p27(kip) in the presence of HLA-G. Together, these
      results indicate that HLA-G is associated with activation of phosphatase SHP-2,
      which inhibits the mTOR pathway and favors the inhibition of the cell-cycle entry
      of human-activated T cells.

PMID- 21887224
TI  - MicroRNA expression data reveals a signature of kidney damage following ischemia
      reperfusion injury.
AB  - Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury, a
      common problem worldwide associated with significant morbidity and mortality. We
      have recently examined the role of microRNAs (miRs) in renal IRI using expression
      profiling. Here we conducted mathematical analyses to determine if differential
      expression of miRs can be used to define a biomarker of renal IRI. Principal
      component analysis (PCA) was combined with spherical geometry to determine
      whether samples that underwent renal injury as a result of IRI can be
      distinguished from controls based on alterations in miR expression using our data
      set consisting of time series measuring 571 miRs. Using PCA, we examined whether
      changes in miR expression in the kidney following IRI have a distinct direction
      when compared to controls based on the trajectory of the first three principal
      components (PCs) for our time series. We then used Monte Carlo methods and
      spherical geometry to assess the statistical significance of these directions. We
      hypothesized that if IRI and control samples exhibit distinct directions, then
      miR expression can be used as a biomarker of injury. Our data reveal that the
      pattern of miR expression in the kidney following IRI has a distinct direction
      based on the trajectory of the first three PCs and can be distinguished from
      changes observed in sham controls. Analyses of samples from immunodeficient mice
      indicated that the changes in miR expression observed following IRI were
      lymphocyte independent, and therefore represent a kidney intrinsic response to
      injury. Together, these data strongly support the notion that IRI results in
      distinct changes in miR expression that can be used as a biomarker of injury.

PMID- 21887226
TI  - Predicting the physiological role of circadian metabolic regulation in the green
      alga Chlamydomonas reinhardtii.
AB  - Although the number of reconstructed metabolic networks is steadily growing,
      experimental data integration into these networks is still challenging. Based on
      elementary flux mode analysis, we combine sequence information with metabolic
      pathway analysis and include, as a novel aspect, circadian regulation. While
      minimizing the need of assumptions, we are able to predict changes in the
      metabolic state and can hypothesise on the physiological role of circadian
      control in nitrogen metabolism of the green alga Chlamydomonas reinhardtii.

PMID- 21887225
TI  - Dominating biological networks.
AB  - Proteins are essential macromolecules of life that carry out most cellular
      processes. Since proteins aggregate to perform function, and since protein
      protein interaction (PPI) networks model these aggregations, one would expect to
      uncover new biology from PPI network topology. Hence, using PPI networks to
      predict protein function and role of protein pathways in disease has received
      attention. A debate remains open about whether network properties of
      "biologically central (BC)" genes (i.e., their protein products), such as those
      involved in aging, cancer, infectious diseases, or signaling and drug-targeted
      pathways, exhibit some topological centrality compared to the rest of the
      proteins in the human PPI network.To help resolve this debate, we design new
      network-based approaches and apply them to get new insight into biological
      function and disease. We hypothesize that BC genes have a topologically central
      (TC) role in the human PPI network. We propose two different concepts of
      topological centrality. We design a new centrality measure to capture complex
      wirings of proteins in the network that identifies as TC those proteins that
      reside in dense extended network neighborhoods. Also, we use the notion of
      domination and find dominating sets (DSs) in the PPI network, i.e., sets of
      proteins such that every protein is either in the DS or is a neighbor of the DS.
      Clearly, a DS has a TC role, as it enables efficient communication between
      different network parts. We find statistically significant enrichment in BC genes
      of TC nodes and outperform the existing methods indicating that genes involved in
      key biological processes occupy topologically complex and dense regions of the
      network and correspond to its "spine" that connects all other network parts and
      can thus pass cellular signals efficiently throughout the network. To our
      knowledge, this is the first study that explores domination in the context of PPI
      networks.

PMID- 21887227
TI  - Photosynthetic responses to heat treatments at different temperatures and
      following recovery in grapevine (Vitis amurensis L.) leaves.
AB  - BACKGROUND: The electron transport chain, Rubisco and stomatal conductance are
      important in photosynthesis. Little is known about their combined responses to
      heat treatment at different temperatures and following recovery in grapevines
      (Vitis spp.) which are often grown in climates with high temperatures.
      METHODOLOGY/FINDINGS: The electron transport function of photosystem II, the
      activation state of Rubisco and the influence of stomatal behavior were
      investigated in grapevine leaves during heat treatments and following recovery.
      High temperature treatments included 35, 40 and 45 degrees C, with 25 degrees C
      as the control and recovery temperature. Heat treatment at 35 degrees C did not
      significantly (P>0.05) inhibit net photosynthetic rate (P(n)). However, with
      treatments at 40 and 45 degrees C, P(n) was decreased, accompanied by an increase
      in substomatal CO(2) concentration (C(i)), decreases in stomatal conductance
      (g(s)) and the activation state of Rubisco, and inhibition of the donor side and
      the reaction center of PSII. The acceptor side of PSII was inhibited at 45
      degrees C but not at 40 degrees C. When grape leaves recovered following heat
      treatment, P(n), g(s) and the activation state of Rubisco also increased, and the
      donor side and the reaction center of PSII recovered. The increase in P(n) during
      the recovery period following the second 45 degrees C stress was slower than that
      following the 40 degrees C stress, and these increases corresponded to the donor
      side of PSII and the activation state of Rubisco. CONCLUSIONS: Heat treatment at
      35 degrees C did not significantly (P>0.05) influence photosynthesis. The
      decrease of P(n) in grape leaves exposed to more severe heat stress (40 or 45
      degrees C) was mainly attributed to three factors: the activation state of
      Rubisco, the donor side and the reaction center of PSII. However, the increase of
      P(n) in grape leaves following heat stress was also associated with a stomatal
      response. The acceptor side of PSII in grape leaves was responsive but less
      sensitive to heat stress.

PMID- 21887228
TI  - Phage displayed peptides to avian H5N1 virus distinguished the virus from other
      viruses.
AB  - The purpose of the current study was to identify potential ligands and develop a
      novel diagnostic test to highly pathogenic avian influenza A virus (HPAI),
      subtype H5N1 viruses using phage display technology. The H5N1 viruses were used
      as an immobilized target in a biopanning process using a 12-mer phage display
      random peptide library. After five rounds of panning, three phages expressing
      peptides HAWDPIPARDPF, AAWHLIVALAPN or ATSHLHVRLPSK had a specific binding
      activity to H5N1 viruses were isolated. Putative binding motifs to H5N1 viruses
      were identified by DNA sequencing. In terms of the minimum quantity of viruses,
      the phage-based ELISA was better than antiserum-based ELISA and a manual, semi
      quantitative endpoint RT-PCR for detecting H5N1 viruses. More importantly, the
      selected phages bearing the specific peptides to H5N1 viruses were capable of
      differentiating this virus from other avian viruses in enzyme-linked
      immunosorbent assays.

PMID- 21887229
TI  - Hard-object feeding in sooty mangabeys (Cercocebus atys) and interpretation of
      early hominin feeding ecology.
AB  - Morphology of the dentofacial complex of early hominins has figured prominently
      in the inference of their dietary adaptations. Recent theoretical analysis of
      craniofacial morphology of Australopithecus africanus proposes that skull form in
      this taxon represents adaptation to feeding on large, hard objects. A modern
      analog for this specific dietary specialization is provided by the West African
      sooty mangabey, Cercocebus atys. This species habitually feeds on the large,
      exceptionally hard nuts of Sacoglottis gabonensis, stereotypically crushing the
      seed casings using their premolars and molars. This type of behavior has been
      inferred for A. africanus based on mathematical stress analysis and aspects of
      dental wear and morphology. While postcanine megadontia, premolar enlargement and
      thick molar enamel characterize both A. africanus and C. atys, these features are
      not universally associated with durophagy among living anthropoids. Occlusal
      microwear analysis reveals complex microwear textures in C. atys unlike those
      observed in A. africanus, but more closely resembling textures observed in
      Paranthropus robustus. Since sooty mangabeys process hard objects in a manner
      similar to that proposed for A. africanus, yet do so without the craniofacial
      buttressing characteristic of this hominin, it follows that derived features of
      the australopith skull are sufficient but not necessary for the consumption of
      large, hard objects. The adaptive significance of australopith craniofacial
      morphology may instead be related to the toughness, rather than the hardness, of
      ingested foods.

PMID- 21887231
TI  - Quantifying species' range shifts in relation to climate change: a case study of
      Abies spp. in China.
AB  - Predicting species range shifts in response to climatic change is a central
      aspect of global change studies. An ever growing number of species have been
      modeled using a variety of species distribution models (SDMs). However,
      quantitative studies of the characteristics of range shifts are rare, predictions
      of range changes are hard to interpret, analyze and summarize, and comparisons
      between the various models are difficult to make when the number of species
      modeled is large. Maxent was used to model the distribution of 12 Abies spp. in
      China under current and possible future climate conditions. Two fuzzy set defined
      indices, range increment index (I) and range overlapping index (O), were used to
      quantify range shifts of the chosen species. Correlation analyses were used to
      test the relationships between these indices and species distribution
      characteristics. Our results show that Abies spp. range increments (I) were
      highly correlated with longitude, latitude, and mean roughness of their current
      distributions. Species overlapping (O) was moderately, or not, correlated with
      these parameters. Neither range increments nor overlapping showed any correlation
      with species prevalence. These fuzzy sets defined indices provide ideal measures
      of species range shifts because they are stable and threshold-free. They are
      reliable indices that allow large numbers of species to be described, modeled,
      and compared on a variety of taxonomic levels.

PMID- 21887230
TI  - Mobilisation of hematopoietic CD34+ precursor cells in patients with acute stroke
      is safe--results of an open-labeled non randomized phase I/II trial.
AB  - BACKGROUND: Regenerative strategies in the treatment of acute stroke may have
      great potential. Hematopoietic growth factors mobilize hematopoietic stem cells
      and may convey neuroprotective effects. We examined the safety, potential
      functional and structural changes, and CD34(+) cell-mobilization characteristics
      of G-CSF treatment in patients with acute ischemic stroke. METHODS AND RESULTS:
      Three cohorts of patients (8, 6, and 6 patients per cohort) were treated
      subcutaneously with 2.5, 5, or 10 ug/kg body weight rhG-CSF for 5 consecutive
      days within 12 hrs of onset of acute stroke. Standard treatment included i.v.
      thrombolysis. Safety monitoring consisted of obtaining standardized clinical
      assessment scores, monitoring of CD34(+) stem cells, blood chemistry, serial
      neuroradiology, and neuropsychology. Voxel-guided morphometry (VGM) enabled an
      assessment of changes in the patients' structural parenchyma. 20 patients (mean
      age 55 yrs) were enrolled in this study, 5 of whom received routine thrombolytic
      therapy with r-tPA. G-CSF treatment was discontinued in 4 patients because of
      unrelated adverse events. Mobilization of CD34(+) cells was observed with no
      concomitant changes in blood chemistry, except for an increase in the leukocyte
      count up to 75,500/ul. Neuroradiological and neuropsychological follow-up studies
      did not disclose any specific G-CSF toxicity. VGM findings indicated substantial
      atrophy of related hemispheres, a substantial increase in the CSF space, and a
      localized increase in parenchyma within the ischemic area in 2 patients.
      CONCLUSIONS: We demonstrate a good safety profile for daily administration of G
      CSF when begun within 12 hours after onset of ischemic stroke and, in part in
      combination with routine i.v. thrombolysis. Additional analyses using VGM and a
      battery of neuropsychological tests indicated a positive functional and
      potentially structural effect of G-CSF treatment in some of our patients. TRIAL
      REGISTRATION: German Clinical Trial Register DRKS 00000723.

PMID- 21887232
TI  - FAK regulates intestinal epithelial cell survival and proliferation during
      mucosal wound healing.
AB  - BACKGROUND: Following damage to the intestinal epithelium, restoration of
      epithelial barrier integrity is triggered by a robust proliferative response. In
      other tissues, focal adhesion kinase (FAK) regulates many of the cellular
      processes that are critical for epithelial homeostasis and restitution, including
      cell migration, proliferation and survival. However, few studies to date have
      determined how FAK contributes to mucosal wound healing in vivo. METHODOLOGY AND
      PRINCIPAL FINDINGS: To examine the role of FAK in intestinal epithelial
      homeostasis and during injury, we generated intestinal epithelium (IE)-specific
      conditional FAK knockout mice. Colitis was induced with dextran-sulfate-sodium
      (DSS) and intestinal tissues were analyzed by immunohistochemistry and
      immunoblotting. While intestinal development occurred normally in mice lacking
      FAK, FAK-deficient animals were profoundly susceptible to colitis. The loss of
      epithelial FAK resulted in elevated p53 expression and an increased sensitivity
      to apoptosis, coincident with a failure to upregulate epithelial cell
      proliferation. FAK has been reported to function as a mechanosensor, inducing
      cyclin D1 expression and promoting cell cycle progression under conditions in
      which tissue/matrix stiffness is increased. Collagen deposition, a hallmark of
      inflammatory injury resulting in increased tissue rigidity, was observed in
      control and FAK knockout mice during colitis. Despite this fibrotic response, the
      colonic epithelium in FAK-deficient mice exhibited significantly reduced cyclin
      D1 expression, suggesting that proliferation is uncoupled from fibrosis in the
      absence of FAK. In support of this hypothesis, proliferation of Caco-2 cells
      increased proportionally with matrix stiffness in vitro only under conditions of
      normal FAK expression; FAK depleted cells exhibited reduced proliferation
      concomitant with attenuated cyclin D1 expression. CONCLUSIONS: In the colon, FAK
      functions as a regulator of epithelial cell survival and proliferation under
      conditions of mucosal injury and a mechanosensor of tissue compliance, inducing
      repair-driven proliferation in the colonic epithelium through upregulation of
      cyclin D1.

PMID- 21887233
TI  - Cyclen-based cationic lipids for highly efficient gene delivery towards tumor
      cells.
AB  - BACKGROUND: Gene therapy has tremendous potential for both inherited and acquired
      diseases. However, delivery problems limited their clinical application, and new
      gene delivery vehicles with low cytotoxicity and high transfection efficiency are
      greatly required. METHODS: In this report, we designed and synthesized three
      amphiphilic molecules (L1-L3) with the structures involving 1, 4, 7, 10
      tetraazacyclododecane (cyclen), imidazolium and a hydrophobic dodecyl chain.
      Their interactions with plasmid DNA were studied via electrophoretic gel
      retardation assays, fluorescent quenching experiments, dynamic light scattering
      and transmission electron microscopy. The in vitro gene transfection assay and
      cytotoxicity assay were conducted in four cell lines. RESULTS: Results indicated
      that L1 and L3-formed liposomes could effectively bind to DNA to form well-shaped
      nanoparticles. Combining with neutral lipid DOPE, L3 was found with high
      efficiency in gene transfer in three tumor cell lines including A549, HepG2 and
      H460. The optimized gene transfection efficacy of L3 was nearly 5.5 times more
      efficient than that of the popular commercially available gene delivery agent
      Lipofectamine 2000TM in human lung carcinoma cells A549. In addition, since L1
      and L3 had nearly no gene transfection performance in normal cells HEK293, these
      cationic lipids showed tumor cell-targeting property to a certain extent. No
      significant cytotoxicity was found for the lipoplexes formed by L1-L3, and their
      cytotoxicities were similar to or slightly lower than the lipoplexes prepared
      from Lipofectamine 2000TM. CONCLUSION: Novel cyclen-based cationic lipids for
      effective in vitro gene transfection were founded, and these studies here may
      extend the application areas of macrocyclic polyamines, especially for cyclen.

PMID- 21887234
TI  - Predicting hospital-acquired infections by scoring system with simple parameters.
AB  - BACKGROUND: Hospital-acquired infections (HAI) are associated with increased
      attributable morbidity, mortality, prolonged hospitalization, and economic costs.
      A simple, reliable prediction model for HAI has great clinical relevance. The
      objective of this study is to develop a scoring system to predict HAI that was
      derived from Logistic Regression (LR) and validated by Artificial Neural Networks
      (ANN) simultaneously. METHODOLOGY/PRINCIPAL FINDINGS: A total of 476 patients
      from all the 806 HAI inpatients were included for the study between 2004 and
      2005. A sample of 1,376 non-HAI inpatients was randomly drawn from all the
      admitted patients in the same period of time as the control group. External
      validation of 2,500 patients was abstracted from another academic teaching
      center. Sixteen variables were extracted from the Electronic Health Records (EHR)
      and fed into ANN and LR models. With stepwise selection, the following seven
      variables were identified by LR models as statistically significant: Foley
      catheterization, central venous catheterization, arterial line, nasogastric tube,
      hemodialysis, stress ulcer prophylaxes and systemic glucocorticosteroids. Both
      ANN and LR models displayed excellent discrimination (area under the receiver
      operating characteristic curve [AUC]: 0.964 versus 0.969, p = 0.507) to identify
      infection in internal validation. During external validation, high AUC was
      obtained from both models (AUC: 0.850 versus 0.870, p = 0.447). The scoring
      system also performed extremely well in the internal (AUC: 0.965) and external
      (AUC: 0.871) validations. CONCLUSIONS: We developed a scoring system to predict
      HAI with simple parameters validated with ANN and LR models. Armed with this
      scoring system, infectious disease specialists can more efficiently identify
      patients at high risk for HAI during hospitalization. Further, using parameters
      either by observation of medical devices used or data obtained from EHR also
      provided good prediction outcome that can be utilized in different clinical
      settings.

PMID- 21887235
TI  - The peptidyl prolyl isomerase Rrd1 regulates the elongation of RNA polymerase II
      during transcriptional stresses.
AB  - Rapamycin is an anticancer agent and immunosuppressant that acts by inhibiting
      the TOR signaling pathway. In yeast, rapamycin mediates a profound
      transcriptional response for which the RRD1 gene is required. To further
      investigate this connection, we performed genome-wide location analysis of RNA
      polymerase II (RNAPII) and Rrd1 in response to rapamycin and found that Rrd1
      colocalizes with RNAPII on actively transcribed genes and that both are recruited
      to rapamycin responsive genes. Strikingly, when Rrd1 is lacking, RNAPII remains
      inappropriately associated to ribosomal genes and fails to be recruited to
      rapamycin responsive genes. This occurs independently of TATA box binding protein
      recruitment but involves the modulation of the phosphorylation status of RNAPII
      CTD by Rrd1. Further, we demonstrate that Rrd1 is also involved in various other
      transcriptional stress responses besides rapamycin. We propose that Rrd1 is a
      novel transcription elongation factor that fine-tunes the transcriptional stress
      response of RNAPII.

PMID- 21887236
TI  - Gene flow and hybridization between numerically imbalanced populations of two
      duck species in the Falkland Islands.
AB  - Interspecific hybridization is common in plants and animals, particularly in
      waterfowl (Anatidae). One factor shown to contribute to hybridization is
      restricted mate choice, which can occur when two species occur in sympatry but
      one is rare. The Hubbs principle, or "desperation hypothesis," states that under
      such circumstances the rarer species is more likely to mate with heterospecifics.
      Here we report interspecific hybridization between two waterfowl species that
      coexist in broad sympatry and mixed flocks throughout southern South America.
      Speckled teal (Anas flavirostris) and yellow-billed pintails (Anas georgica) are
      abundant in continental South America, but in the Falkland Islands speckled teal
      outnumber yellow-billed pintails approximately ten to one. Using eight genetic
      loci (mtDNA and 7 nuclear introns) coupled with Bayesian assignment tests and
      relatedness analysis, we identified a speckled teal x yellow-billed pintail F(1)
      hybrid female and her duckling sired by a male speckled teal. Although our sample
      in the Falkland Islands was small, we failed to identify unequivocal evidence of
      hybridization or introgression in a much larger sample from Argentina using a
      three-population "isolation with migration" coalescent analysis. While additional
      data are needed to determine if this event in the Falkland Islands was a rare
      singular occurrence, our results provide further support for the "desperation
      hypothesis," which states that scarcity in one population and abundance of
      another will often lead to hybridization.

PMID- 21887237
TI  - A one-step real-time multiplex PCR for screening Y-chromosomal microdeletions
      without downstream amplicon size analysis.
AB  - BACKGROUND: Y-chromosomal microdeletions (YCMD) are one of the major genetic
      causes for non-obstructive azoospermia. Genetic testing for YCMD by multiplex
      polymerase chain reaction (PCR) is an established method for quick and robust
      screening of deletions in the AZF regions of the Y-chromosome. Multiplex PCRs
      have the advantage of including a control gene in every reaction and
      significantly reducing the number of reactions needed to screen the relevant
      genomic markers. PRINCIPAL FINDINGS: The widely established "EAA/EMQN best
      practice guidelines for molecular diagnosis of Y-chromosomal microdeletions
      (2004)" were used as a basis for designing a real-time multiplex PCR system, in
      which the YCMD can simply be identified by their melting points. For this reason,
      some AZF primers were substituted by primers for regions in their genomic
      proximity, and the ZFX/ZFY control primer was exchanged by the AMELX/AMELY
      control primer. Furthermore, we substituted the classical SybrGreen I dye by the
      novel and high-performing DNA-binding dye EvaGreenTM and put substantial effort
      in titrating the primer combinations in respect to optimal melting peak
      separation and peak size. SIGNIFICANCE: With these changes, we were able to
      develop a platform-independent and robust real-time based multiplex PCR, which
      makes the need for amplicon identification by electrophoretic sizing expendable.
      By using an open-source system for real-time PCR analysis, we further demonstrate
      the applicability of automated melting point and YCMD detection.

PMID- 21887238
TI  - Is chytridiomycosis an emerging infectious disease in Asia?
AB  - The disease chytridiomycosis, caused by the fungus Batrachochytrium dendrobatidis
      (Bd), has caused dramatic amphibian population declines and extinctions in
      Australia, Central and North America, and Europe. Bd is associated with >200
      species extinctions of amphibians, but not all species that become infected are
      susceptible to the disease. Specifically, Bd has rapidly emerged in some areas of
      the world, such as in Australia, USA, and throughout Central and South America,
      causing population and species collapse. The mechanism behind the rapid global
      emergence of the disease is poorly understood, in part due to an incomplete
      picture of the global distribution of Bd. At present, there is a considerable
      amount of geographic bias in survey effort for Bd, with Asia being the most
      neglected continent. To date, Bd surveys have been published for few Asian
      countries, and infected amphibians have been reported only from Indonesia, South
      Korea, China and Japan. Thus far, there have been no substantiated reports of
      enigmatic or suspected disease-caused population declines of the kind that has
      been attributed to Bd in other areas. In order to gain a more detailed picture of
      the distribution of Bd in Asia, we undertook a widespread, opportunistic survey
      of over 3,000 amphibians for Bd throughout Asia and adjoining Papua New Guinea.
      Survey sites spanned 15 countries, approximately 36 degrees  latitude, 111
      degrees  longitude, and over 2000 m in elevation. Bd prevalence was very low
      throughout our survey area (2.35% overall) and infected animals were not clumped
      as would be expected in epizootic events. This suggests that Bd is either newly
      emerging in Asia, endemic at low prevalence, or that some other ecological factor
      is preventing Bd from fully invading Asian amphibians. The current observed
      pattern in Asia differs from that in many other parts of the world.

PMID- 21887239
TI  - Ostriches sleep like platypuses.
AB  - Mammals and birds engage in two distinct states of sleep, slow wave sleep (SWS)
      and rapid eye movement (REM) sleep. SWS is characterized by slow, high amplitude
      brain waves, while REM sleep is characterized by fast, low amplitude waves, known
      as activation, occurring with rapid eye movements and reduced muscle tone.
      However, monotremes (platypuses and echidnas), the most basal (or 'ancient')
      group of living mammals, show only a single sleep state that combines elements of
      SWS and REM sleep, suggesting that these states became temporally segregated in
      the common ancestor to marsupial and eutherian mammals. Whether sleep in basal
      birds resembles that of monotremes or other mammals and birds is unknown. Here,
      we provide the first description of brain activity during sleep in ostriches
      (Struthio camelus), a member of the most basal group of living birds. We found
      that the brain activity of sleeping ostriches is unique. Episodes of REM sleep
      were delineated by rapid eye movements, reduced muscle tone, and head movements,
      similar to those observed in other birds and mammals engaged in REM sleep;
      however, during REM sleep in ostriches, forebrain activity would flip between REM
      sleep-like activation and SWS-like slow waves, the latter reminiscent of sleep in
      the platypus. Moreover, the amount of REM sleep in ostriches is greater than in
      any other bird, just as in platypuses, which have more REM sleep than other
      mammals. These findings reveal a recurring sequence of steps in the evolution of
      sleep in which SWS and REM sleep arose from a single heterogeneous state that
      became temporally segregated into two distinct states. This common trajectory
      suggests that forebrain activation during REM sleep is an evolutionarily new
      feature, presumably involved in performing new sleep functions not found in more
      basal animals.

PMID- 21887240
TI  - Functional effects of parasites on food web properties during the spring diatom
      bloom in Lake Pavin: a linear inverse modeling analysis.
AB  - This study is the first assessment of the quantitative impact of parasitic
      chytrids on a planktonic food web. We used a carbon-based food web model of Lake
      Pavin (Massif Central, France) to investigate the effects of chytrids during the
      spring diatom bloom by developing models with and without chytrids. Linear
      inverse modelling procedures were employed to estimate undetermined flows in the
      lake. The Monte Carlo Markov chain linear inverse modelling procedure provided
      estimates of the ranges of model-derived fluxes. Model results support recent
      theories on the probable impact of parasites on food web function. In the lake,
      during spring, when 'inedible' algae (unexploited by planktonic herbivores) were
      the dominant primary producers, the epidemic growth of chytrids significantly
      reduced the sedimentation loss of algal carbon to the detritus pool through the
      production of grazer-exploitable zoospores. We also review some theories about
      the potential influence of parasites on ecological network properties and argue
      that parasitism contributes to longer carbon path lengths, higher levels of
      activity and specialization, and lower recycling. Considering the "structural
      asymmetry" hypothesis as a stabilizing pattern, chytrids should contribute to the
      stability of aquatic food webs.

PMID- 21887241
TI  - Generalized fragment picking in Rosetta: design, protocols and applications.
AB  - The Rosetta de novo structure prediction and loop modeling protocols begin with
      coarse grained Monte Carlo searches in which the moves are based on short
      fragments extracted from a database of known structures. Here we describe a new
      object oriented program for picking fragments that greatly extends the
      functionality of the previous program (nnmake) and opens the door for new
      approaches to structure modeling. We provide a detailed description of the code
      design and architecture, highlighting its modularity, and new features such as
      extensibility, total control over the fragment picking workflow and scoring
      system customization. We demonstrate that the program provides at least as good
      building blocks for ab-initio structure prediction as the previous program, and
      provide examples of the wide range of applications that are now accessible.

PMID- 21887242
TI  - Variability of female responses to conspecific vs. heterospecific male mating
      calls in polygynous deer: an open door to hybridization?
AB  - Males of all polygynous deer species (Cervinae) give conspicuous calls during the
      reproductive season. The extreme interspecific diversity that characterizes these
      vocalizations suggests that they play a strong role in species discrimination.
      However, interbreeding between several species of Cervinae indicates permeable
      interspecific reproductive barriers. This study examines the contribution of
      vocal behavior to female species discrimination and mating preferences in two
      closely related polygynous deer species known to hybridize in the wild after
      introductions. Specifically, we investigate the reaction of estrous female red
      deer (Cervus elaphus) to playbacks of red deer vs. sika deer (Cervus nippon) male
      mating calls, with the prediction that females will prefer conspecific calls.
      While on average female red deer preferred male red deer roars, two out of twenty
      females spent more time in close proximity to the speaker broadcasting male sika
      deer moans. We suggest that this absence of strict vocal preference for species
      specific mating calls may contribute to the permeability of pre-zygotic
      reproductive barriers observed between these species. Our results also highlight
      the importance of examining inter-individual variation when studying the role of
      female preferences in species discrimination and intraspecific mate selection.

PMID- 21887245
TI  - Semi-Markov graph dynamics.
AB  - In this paper, we outline a model of graph (or network) dynamics based on two
      ingredients. The first ingredient is a Markov chain on the space of possible
      graphs. The second ingredient is a semi-Markov counting process of renewal type.
      The model consists in subordinating the Markov chain to the semi-Markov counting
      process. In simple words, this means that the chain transitions occur at random
      time instants called epochs. The model is quite rich and its possible connections
      with algebraic geometry are briefly discussed. Moreover, for the sake of
      simplicity, we focus on the space of undirected graphs with a fixed number of
      nodes. However, in an example, we present an interbank market model where it is
      meaningful to use directed graphs or even weighted graphs.

PMID- 21887244
TI  - Rhesus monkeys see who they hear: spontaneous cross-modal memory for familiar
      conspecifics.
AB  - Rhesus monkeys gather much of their knowledge of the social world through visual
      input and may preferentially represent this knowledge in the visual modality.
      Recognition of familiar faces is clearly advantageous, and the flexibility and
      utility of primate social memory would be greatly enhanced if visual memories
      could be accessed cross-modally either by visual or auditory stimulation. Such
      cross-modal access to visual memory would facilitate flexible retrieval of the
      knowledge necessary for adaptive social behavior. We tested whether rhesus
      monkeys have cross-modal access to visual memory for familiar conspecifics using
      a delayed matching-to-sample procedure. Monkeys learned visual matching of video
      clips of familiar individuals to photographs of those individuals, and
      generalized performance to novel videos. In crossmodal probe trials, coo-calls
      were played during the memory interval. The calls were either from the monkey
      just seen in the sample video clip or from a different familiar monkey. Even
      though the monkeys were trained exclusively in visual matching, the calls
      influenced choice by causing an increase in the proportion of errors to the
      picture of the monkey whose voice was heard on incongruent trials. This result
      demonstrates spontaneous cross-modal recognition. It also shows that viewing
      videos of familiar monkeys activates naturally formed memories of real monkeys,
      validating the use of video stimuli in studies of social cognition in monkeys.

PMID- 21887246
TI  - Estimating incidence curves of several infections using symptom surveillance
      data.
AB  - We introduce a method for estimating incidence curves of several co-circulating
      infectious pathogens, where each infection has its own probabilities of
      particular symptom profiles. Our deconvolution method utilizes weekly
      surveillance data on symptoms from a defined population as well as additional
      data on symptoms from a sample of virologically confirmed infectious episodes. We
      illustrate this method by numerical simulations and by using data from a survey
      conducted on the University of Michigan campus. Last, we describe the data needs
      to make such estimates accurate.

PMID- 21887247
TI  - Curcumin-loaded apotransferrin nanoparticles provide efficient cellular uptake
      and effectively inhibit HIV-1 replication in vitro.
AB  - BACKGROUND: Curcumin (diferuloylmethane) shows significant activity across a wide
      spectrum of conditions, but its usefulness is rather limited because of its low
      bioavailability. Use of nanoparticle formulations to enhance curcumin
      bioavailability is an emerging area of research. METHODOLOGY/PRINCIPAL FINDINGS:
      In the present study, curcumin-loaded apotransferrin nanoparticles (nano
      curcumin) prepared by sol-oil chemistry and were characterized by electron and
      atomic force microscopy. Confocal studies and fluorimetric analysis revealed that
      these particles enter T cells through transferrin-mediated endocytosis. Nano
      curcumin releases significant quantities of drug gradually over a fairly long
      period, ~50% of curcumin still remaining at 6 h of time. In contrast,
      intracellular soluble curcumin (sol-curcumin) reaches a maximum at 2 h followed
      by its complete elimination by 4 h. While sol-curcumin (GI(50) = 15.6 uM) is
      twice more toxic than nano-curcumin (GI(50) = 32.5 uM), nano-curcumin
      (IC(50)<1.75 uM) shows a higher anti-HIV activity compared to sol-curcumin
      (IC(50) = 5.1 uM). Studies in vitro showed that nano-curcumin prominently
      inhibited the HIV-1 induced expression of Topo II alpha, IL-1beta and COX-2, an
      effect not seen with sol-curcumin. Nano-curcumin did not affect the expression of
      Topoisomerase II beta and TNF alpha. This point out that nano-curcumin affects
      the HIV-1 induced inflammatory responses through pathways downstream or
      independent of TNF alpha. Furthermore, nano-curcumin completely blocks the
      synthesis of viral cDNA in the gag region suggesting that the nano-curcumin
      mediated inhibition of HIV-1 replication is targeted to viral cDNA synthesis.
      CONCLUSION: Curcumin-loaded apotransferrin nanoparticles are highly efficacious
      inhibitors of HIV-1 replication in vitro and promise a high potential for
      clinical usefulness.

PMID- 21887248
TI  - Resveratrol and black tea polyphenol combination synergistically suppress mouse
      skin tumors growth by inhibition of activated MAPKs and p53.
AB  - Cancer chemoprevention by natural dietary agents has received considerable
      importance because of their cost-effectiveness and wide safety margin. However,
      single agent intervention has failed to bring the expected outcome in clinical
      trials; therefore, combinations of chemopreventive agents are gaining increasing
      popularity. The present study aims to evaluate the combinatorial chemopreventive
      effects of resveratrol and black tea polyphenol (BTP) in suppressing two-stage
      mouse skin carcinogenesis induced by DMBA and TPA. Resveratrol/BTP alone
      treatment decreased tumor incidence by ~67% and ~75%, while combination of both
      at low doses synergistically decreased tumor incidence even more significantly by
      ~89% (p<0.01). This combination also significantly regressed tumor volume and
      number (p<0.01). Mechanistic studies revealed that this combinatorial inhibition
      was associated with decreased expression of phosphorylated mitogen-activated
      protein kinase family proteins: extracellular signal-regulated kinase 1/2, c-Jun
      N-terminal kinase 1/2, p38 and increased in total p53 and phospho p53 (Ser 15) in
      skin tissue/tumor. Treatment with combinations of resveratrol and BTP also
      decreased expression of proliferating cell nuclear antigen in mouse skin
      tissues/tumors than their solitary treatments as determined by
      immunohistochemistry. In addition, histological and cell death analysis also
      confirmed that resveratrol and BTP treatment together inhibits cellular
      proliferation and markedly induces apoptosis. Taken together, our results for the
      first time lucidly illustrate that resveratrol and BTP in combination impart
      better suppressive activity than either of these agents alone and accentuate that
      development of novel combination therapies/chemoprevention using dietary agents
      will be more beneficial against cancer. This promising combination should be
      examined in therapeutic trials of skin and possibly other cancers.

PMID- 21887249
TI  - Systematic clustering of transcription start site landscapes.
AB  - Genome-wide, high-throughput methods for transcription start site (TSS) detection
      have shown that most promoters have an array of neighboring TSSs where some are
      used more than others, forming a distribution of initiation propensities. TSS
      distributions (TSSDs) vary widely between promoters and earlier studies have
      shown that the TSSDs have biological implications in both regulation and
      function. However, no systematic study has been made to explore how many types of
      TSSDs and by extension core promoters exist and to understand which biological
      features distinguish them. In this study, we developed a new non-parametric
      dissimilarity measure and clustering approach to explore the similarities and
      stabilities of clusters of TSSDs. Previous studies have used arbitrary thresholds
      to arrive at two general classes: broad and sharp. We demonstrated that in
      addition to the previous broad/sharp dichotomy an additional category of
      promoters exists. Unlike typical TATA-driven sharp TSSDs where the TSS position
      can vary a few nucleotides, in this category virtually all TSSs originate from
      the same genomic position. These promoters lack epigenetic signatures of typical
      mRNA promoters and a substantial subset of them are mapping upstream of ribosomal
      protein pseudogenes. We present evidence that these are likely mapping errors,
      which have confounded earlier analyses, due to the high similarity of ribosomal
      gene promoters in combination with known G addition bias in the CAGE libraries.
      Thus, previous two-class separations of promoter based on TSS distributions are
      motivated, but the ultra-sharp TSS distributions will confound downstream
      analyses if not removed.

PMID- 21887250
TI  - Critical role of PI3K/Akt/GSK3beta in motoneuron specification from human neural
      stem cells in response to FGF2 and EGF.
AB  - Fibroblast growth factor (FGF) and epidermal growth factor (EGF) are critical for
      the development of the nervous system. We previously discovered that FGF2 and EGF
      had opposite effects on motor neuron differentiation from human fetal neural stem
      cells (hNSCs), but the underlying mechanisms remain unclear. Here, we show that
      FGF2 and EGF differentially affect the temporal patterns of Akt and glycogen
      synthase kinase 3 beta (GSK3beta) activation. High levels of phosphatidylinositol
      3-kinase (PI3K)/Akt activation accompanied with GSK3beta inactivation result in
      reduction of the motor neuron transcription factor HB9. Inhibition of PI3K/Akt by
      chemical inhibitors or RNA interference or overexpression of a constitutively
      active form of GSK3beta enhances HB9 expression. Consequently, PI3K inhibition
      increases hNSCs differentiation into HB9(+)/microtubule-associated protein 2
      (MAP2)(+) motor neurons in vitro. More importantly, blocking PI3K not only
      enhances motor neuron differentiation from hNSCs grafted into the ventral horn of
      adult rat spinal cords, but also permits ectopic generation of motor neurons in
      the dorsal horn by overriding environmental influences. Our data suggest that
      FGF2 and EGF affect the motor neuron fate decision in hNSCs differently through a
      fine tuning of the PI3K/AKT/GSK3beta pathway, and that manipulation of this
      pathway can enhance motor neuron generation.

PMID- 21887243
TI  - X4 tropic multi-drug resistant quasi-species detected at the time of primary HIV
      1 infection remain exclusive or at least dominant far from PHI.
AB  - Our objective was to analyze the evolution of resistance mutations (RM) and viral
      tropism of multi-drug-resistant (MDR) strains detected at primary HIV-1 infection
      (PHI). MDR HIV strain was defined as the presence of genotypic resistance to at
      least 1 antiretroviral of the 3 classes. Tropism determinations (CCR5 or CXCR4)
      were performed on baseline plasma HIV-RNA and/or PBMC-HIV-DNA samples, then
      during follow-up using population-based sequencing of V3 loop and phenotypic
      tests. Clonal analysis was performed at baseline for env, RT and protease genes,
      and for HIV-DNA env gene during follow-up. Five patients were eligible. At
      baseline, RT, protease and env clones from HIV-RNA and HIV-DNA were highly
      homogenous for each patient; genotypic tropism was R5 in 3 (A,B,C) and X4 in 2
      patients (D,E). MDR strains persisted in HIV-DNA throughout follow-up in all
      patients. For patient A, tropism remained R5 with concordance between phenotypic
      and genotypic tests. Clonal analysis on Month (M) 78 HIV-DNA evidenced
      exclusively R5 (21/21) variants. In patient B, clonal analysis at M36 showed
      exclusively R5 variants (19/19) using both genotypic and phenotypic tests. In
      patient C, baseline tropism was R5 by genotypic test and R5/X4 by phenotypic
      test. An expansion of these X4 clones was evidenced by clonal analysis on M72 HIV
      DNA (12/14 X4 and 2/14 R5 variants). In patient D, baseline tropism was X4 with
      concordance between both techniques and HIV-RNA and HIV-DNA remained X4-tropic up
      to M72, confirmed by the clonal analysis. Patient E harboured highly homogenous
      X4-using population at baseline; tropism was unchanged at M1 and M18. In all
      patients, the initial MDR population was highly homogenous initially, supporting
      the early expansion of a monoclonal population and its long-term persistence. X4
      tropic variants present at baseline were still exclusive (patients D and E) or
      dominant (at least one time point, patient C) far from PHI.

PMID- 21887251
TI  - HIV incidence among men who have sex with men in China: a meta-analysis of
      published studies.
AB  - BACKGROUND: Men who have sex with men (MSM) have now become one of the priority
      populations for prevention and control of HIV pandemic in China. Information of
      HIV incidence among MSM is important to describe the spreading of the infection
      and predict its trends in this population. We reviewed the published literature
      on the incidence of HIV infection among MSM in China. METHODS: We identified
      relevant studies by use of a comprehensive strategy including searches of Medline
      and two Chinese electronic publication databases from January 2005 to September
      2010. Point estimate of random effects incidence with corresponding 95%
      confidence intervals (CI) of HIV infection was carried out using the
      Comprehensive Meta-Analysis software. Subgroup analyses were examined separately,
      stratified by study design and geographic location. RESULTS: Twelve studies were
      identified, including three cohort studies and nine cross-sectional studies. The
      subgroup analyses revealed that the sub-overall incidence estimates were 3.5%
      (95% CI, 1.7%-5.3%) and 6.7% (95% CI, 4.8%-8.6%) for cohort and cross-sectional
      studies, respectively (difference between the sub-overalls, Q = 5.54, p = 0.02);
      and 8.3% (95% CI, 6.9%-9.7%) and 4.6% (95% CI, 2.4%-6.9%) for studies in
      Chongqing and other areas, respectively (difference between the sub-overalls, Q =
      7.58, p<0.01). Syphilis infection (RR = 3.33, p<0.001), multiple sex partnerships
      (RR = 2.81, p<0.001), and unprotected receptive anal intercourse in the past six
      months (RR = 3.88, p = 0.007) represented significant risk for HIV
      seroconversion. CONCLUSIONS: Findings from this meta-analysis indicate that HIV
      incidence is substantial in MSM in China. High incidence of HIV infection and
      unique patterns of sexual risk behaviors in this population serve as a call for
      action that should be answered with the innovative social and public health
      intervention strategies, and development of biological prevention strategies.

PMID- 21887253
TI  - MicroRNA profiling in subventricular zone after stroke: MiR-124a regulates
      proliferation of neural progenitor cells through Notch signaling pathway.
AB  - BACKGROUND: The Notch signaling pathway regulates adult neurogenesis under
      physiological and pathophysiological conditions. MicroRNAs are small non-coding
      RNA molecules that regulate gene expression. The present study investigated the
      effect of miR-124a on the Notch signaling pathway in stroke-induced neurogenesis.
      METHODOLOGY AND PRINCIPAL FINDINGS: We found that adult rats subjected to focal
      cerebral ischemia exhibited substantial reduction of miR-124a expression, a
      neuron specific miRNA, in the neural progenitor cells of the subventricular zone
      (SVZ) of the lateral ventricle, which was inversely associated with activation of
      Notch signals. In vitro, transfection of neural progenitor cells harvested from
      the SVZ of adult rat with miR-124a repressed Jagged-1 (JAG1), a ligand of Notch,
      in a luciferase construct containing the JAG1 target site. Introduction of miR
      124a in neural progenitor cells significantly reduced JAG1 transcript and protein
      levels, leading to inactivation of Notch signals. Transfection of neural
      progenitor cells with miR-124a significantly reduced progenitor cell
      proliferation and promoted neuronal differentiation measured by an increase in
      the number of Doublecortin positive cells, a marker of neuroblasts. Furthermore,
      introduction of miR-124a significantly increased p27Kip1 mRNA and protein levels,
      a downstream target gene of the Notch signaling pathway. CONCLUSIONS:
      Collectively, our study demonstrated that in vivo, stroke alters miRNA expression
      in SVZ neural progenitor cells and that in vitro, miR-124a mediates stroke
      induced neurogenesis by targeting the JAG-Notch signaling pathway.

PMID- 21887252
TI  - A peptide mimetic targeting trans-homophilic NCAM binding sites promotes spatial
      learning and neural plasticity in the hippocampus.
AB  - The key roles played by the neural cell adhesion molecule (NCAM) in plasticity
      and cognition underscore this membrane protein as a relevant target to develop
      cognitive-enhancing drugs. However, NCAM is a structurally and functionally
      complex molecule with multiple domains engaged in a variety of actions, which
      raise the question as to which NCAM fragment should be targeted. Synthetic NCAM
      mimetic peptides that mimic NCAM sequences relevant to specific interactions
      allow identification of the most promising targets within NCAM. Recently, a
      decapeptide ligand of NCAM--plannexin, which mimics a homophilic trans-binding
      site in Ig2 and binds to Ig3--was developed as a tool for studying NCAM's trans
      interactions. In this study, we investigated plannexin's ability to affect neural
      plasticity and memory formation. We found that plannexin facilitates neurite
      outgrowth in primary hippocampal neuronal cultures and improves spatial learning
      in rats, both under basal conditions and under conditions involving a deficit in
      a key plasticity-promoting posttranslational modification of NCAM, its
      polysialylation. We also found that plannexin enhances excitatory synaptic
      transmission in hippocampal area CA1, where it also increases the number of
      mushroom spines and the synaptic expression of the AMPAR subunits GluA1 and
      GluA2. Altogether, these findings provide compelling evidence that plannexin is
      an important facilitator of synaptic functional, structural and molecular
      plasticity in the hippocampal CA1 region, highlighting the fragment in NCAM's Ig3
      module where plannexin binds as a novel target for the development of cognition
      enhancing drugs.

PMID- 21887254
TI  - Th1/Th17 cell induction and corresponding reduction in ATP consumption following
      vaccination with the novel Mycobacterium tuberculosis vaccine MVA85A.
AB  - Vaccination with Bacille Calmette-Guerin (BCG) has traditionally been used for
      protection against disease caused by the bacterium Mycobacterium tuberculosis
      (M.tb). The efficacy of BCG, especially against pulmonary tuberculosis (TB) is
      variable. The best protection is conferred in temperate climates and there is
      close to zero protection in many tropical areas with a high prevalence of both
      tuberculous and non-tuberculous mycobacterial species. Although interferon (IFN)
      gamma is known to be important in protection against TB disease, data is emerging
      on a possible role for interleukin (IL)-17 as a key cytokine in both murine and
      bovine TB vaccine studies, as well as in humans. Modified Vaccinia virus Ankara
      expressing Antigen 85A (MVA85A) is a novel TB vaccine designed to enhance
      responses induced by BCG. Antigen-specific IFN-gamma production has already been
      shown to peak one week post-MVA85A vaccination, and an inverse relationship
      between IL-17-producing cells and regulatory T cells expressing the
      ectonucleosidease CD39, which metabolises pro-inflammatory extracellular ATP has
      previously been described. This paper explores this relationship and finds that
      consumption of extracellular ATP by peripheral blood mononuclear cells from
      MVA85A-vaccinated subjects drops two weeks post-vaccination, corresponding to a
      drop in the percentage of a regulatory T cell subset expressing the
      ectonucleosidase CD39. Also at this time point, we report a peak in co-production
      of IL-17 and IFN-gamma by CD4(+) T cells. These results suggest a relationship
      between extracellular ATP and effector responses and unveil a possible pathway
      that could be targeted during vaccine design.

PMID- 21887255
TI  - The natural cytotoxicity receptor 1 contribution to early clearance of
      Streptococcus pneumoniae and to natural killer-macrophage cross talk.
AB  - Natural killer (NK) cells serve as a crucial first line of defense against
      tumors, viral and bacterial infections. We studied the involvement of a principal
      activating natural killer cell receptor, natural cytotoxicity receptor 1 (NCR1),
      in the innate immune response to S. pneumoniae infection. Our results demonstrate
      that the presence of the NCR1 receptor is imperative for the early clearance of
      S. pneumoniae. We tied the ends in vivo by showing that deficiency in NCR1
      resulted in reduced lung NK cell activation and lung IFNgamma production at the
      early stages of S. pneumoniae infection. NCR1 did not mediate direct recognition
      of S. pneumoniae. Therefore, we studied the involvement of lung macrophages and
      dendritic cells (DC) as the mediators of NK-expressed NCR1 involvement in
      response to S. pneumoniae. In vitro, wild type BM-derived macrophages and DC
      expressed ligands to NCR1 and co-incubation of S. pneumoniae-infected
      macrophages/DC with NCR1-deficient NK cells resulted in significantly lesser
      IFNgamma levels compared to NCR1-expressing NK cells. In vivo, ablation of lung
      macrophages and DC was detrimental to the early clearance of S. pneumoniae. NCR1
      expressing mice had more potent alveolar macrophages as compared to NCR1
      deficient mice. This result correlated with the higher fraction of NCR1
      ligand(high) lung macrophages, in NCR1-expressing mice, that had better
      phagocytic activity compared to NCR1-ligand(dull) macrophages. Overall, our
      results point to the essential contribution of NK-expressed NCR1 in early
      response to S. pneumoniae infection and to NCR1-mediated interaction of NK and S.
      pneumoniae infected-macrophages and -DC.

PMID- 21887256
TI  - BPR1K653, a novel Aurora kinase inhibitor, exhibits potent anti-proliferative
      activity in MDR1 (P-gp170)-mediated multidrug-resistant cancer cells.
AB  - BACKGROUND: Over-expression of Aurora kinases promotes the tumorigenesis of
      cells. The aim of this study was to determine the preclinical profile of a novel
      pan-Aurora kinase inhibitor, BPR1K653, as a candidate for anti-cancer therapy.
      Since expression of the drug efflux pump, MDR1, reduces the effectiveness of
      various chemotherapeutic compounds in human cancers, this study also aimed to
      determine whether the potency of BPR1K653 could be affected by the expression of
      MDR1 in cancer cells. PRINCIPAL FINDINGS: BPR1K653 specifically inhibited the
      activity of Aurora-A and Aurora-B kinase at low nano-molar concentrations in
      vitro. Anti-proliferative activity of BPR1K653 was evaluated in various human
      cancer cell lines. Results of the clonogenic assay showed that BPR1K653 was
      potent in targeting a variety of cancer cell lines regardless of the tissue
      origin, p53 status, or expression of MDR1. At the cellular level, BPR1K653
      induced endo-replication and subsequent apoptosis in both MDR1-negative and MDR1
      positive cancer cells. Importantly, it showed potent activity against the growth
      of xenograft tumors of the human cervical carcinoma KB and KB-derived MDR1
      positive KB-VIN10 cells in nude mice. Finally, BPR1K653 also exhibited favorable
      pharmacokinetic properties in rats. CONCLUSIONS AND SIGNIFICANCE: BPR1K653 is a
      novel potent anti-cancer compound, and its potency is not affected by the
      expression of the multiple drug resistant protein, MDR1, in cancer cells.
      Therefore, BPR1K653 is a promising anti-cancer compound that has potential for
      the management of various malignancies, particularly for patients with MDR1
      related drug resistance after prolonged chemotherapeutic treatments.

PMID- 21887258
TI  - Smyd3 is required for the development of cardiac and skeletal muscle in
      zebrafish.
AB  - Modifications of histone tails are involved in the regulation of a wide range of
      biological processes including cell cycle, cell survival, cell division, and cell
      differentiation. Among the modifications, histone methylation plays a critical
      role in cardiac and skeletal muscle differentiation. In our earlier studies, we
      found that SMYD3 has methyltransferase activity to histone H3 lysine 4, and that
      its up-regulation is involved in the tumorigenesis of human colon, liver, and
      breast. To clarify the role of Smyd3 in development, we have studied its
      expression patterns in zebrafish embryos and the effect of its suppression on
      development using Smyd3-specific antisense morpholino-oligonucleotides. We here
      show that transcripts of smyd3 were expressed in zebrafish embryos at all
      developmental stages examined and that knockdown of smyd3 in embryos resulted in
      pericardial edema and defects in the trunk structure. In addition, these
      phenotypes were associated with abnormal expression of three heart-chamber
      markers including cmlc2, amhc and vmhc, and abnormal expression of myogenic
      regulatory factors including myod and myog. These data suggest that Smyd3 plays
      an important role in the development of heart and skeletal muscle.

PMID- 21887257
TI  - NF-kappaB inducing kinase, NIK mediates cigarette smoke/TNFalpha-induced histone
      acetylation and inflammation through differential activation of IKKs.
AB  - BACKGROUND: Nuclear factor (NF)-kappaB inducing kinase (NIK) is a central player
      in the non-canonical NF kappaB pathway, which phosphorylates IkappaB kinase alpha
      (IKKalpha) resulting in enhancement of target gene expression. We have recently
      shown that IKKalpha responds to a variety of stimuli including oxidants and
      cigarette smoke (CS) regulating the histone modification in addition to its role
      in NF-kappaB activation. However, the primary signaling mechanism linking CS
      mediated oxidative stress and TNFalpha with histone acetylation and pro
      inflammatory gene transcription is not well understood. We hypothesized that CS
      and TNFalpha increase NIK levels causing phosphorylation of IKKalpha, which leads
      to histone acetylation. METHODOLOGY: To test this hypothesis, we investigated
      whether NIK mediates effects of CS and TNFalpha on histone acetylation in human
      lung epithelial cells in vitro and in lungs of mouse exposed to CS in vivo. CS
      increased the phosphorylation levels of IKKalpha/NIK in lung epithelial cells and
      mouse lungs. NIK is accumulated in the nuclear compartment, and is recruited to
      the promoters of pro-inflammatory genes, to induce posttranslational acetylation
      of histones in response to CS and TNFalpha. Cells in which NIK is knocked down
      using siRNA showed partial attenuation of CSE- and TNFalpha-induced acetylation
      of histone H3 on pro-inflammatory gene promoters. Additional study to determine
      the role of IKKbeta/NF-kappaB pathway in CS-induced histone acetylation suggests
      that the canonical pathway does not play a role in histone acetylation
      particularly in response to CS in mouse lungs. CONCLUSIONS: Overall, our findings
      provide a novel role for NIK in CS- and TNFalpha-induced histone acetylation,
      especially on histone H3K9.

PMID- 21887259
TI  - Reduction of claustrophobia with short-bore versus open magnetic resonance
      imaging: a randomized controlled trial.
AB  - BACKGROUND: Claustrophobia is a common problem precluding MR imaging. The purpose
      of the present study was to assess whether a short-bore or an open magnetic
      resonance (MR) scanner is superior in alleviating claustrophobia. METHODS:
      Institutional review board approval and patient informed consent were obtained to
      compare short-bore versus open MR. From June 2008 to August 2009, 174 patients
      (139 women; mean age = 53.1 [SD 12.8]) with an overall mean score of 2.4 (SD 0.7,
      range 0 to 4) on the Claustrophobia Questionnaire (CLQ) and a clinical indication
      for imaging, were randomly assigned to receive evaluation by open or by short
      bore MR. The primary outcomes were incomplete MR examinations due to a
      claustrophobic event. Follow-up was conducted 7 months after MR imaging. The
      primary analysis was performed according to the intention-to-treat strategy.
      RESULTS: With 33 claustrophobic events in the short-bore group (39% [95%
      confidence interval [CI] 28% to 50%) versus 23 in the open scanner group (26%
      [95% CI 18% to 37%]; P = 0.08) the difference was not significant. Patients with
      an event were in the examination room for 3.8 min (SD 4.4) in the short-bore and
      for 8.5 min (SD 7) in the open group (P = 0.004). This was due to an earlier
      occurrence of events in the short-bore group. The CLQ suffocation subscale was
      significantly associated with the occurrence of claustrophobic events (P =
      0.003). New findings that explained symptoms were found in 69% of MR examinations
      and led to changes in medical treatment in 47% and surgery in 10% of patients.
      After 7 months, perceived claustrophobia increased in 32% of patients with events
      versus in only 11% of patients without events (P = 0.004). CONCLUSIONS: Even
      recent MR cannot prevent claustrophobia suggesting that further developments to
      create a more patient-centered MR scanner environment are needed. TRIAL
      REGISTRATION: ClinicalTrials.gov NCT00715806.

PMID- 21887260
TI  - Comprehensive study in the inhibitory effect of berberine on gene transcription,
      including TATA box.
AB  - Berberine (BBR) is an established natural DNA intercalator with numerous
      pharmacological functions. However, currently there are neither detailed reports
      concerning the distribution of this alkaloid in living cells nor reports
      concerning the relationship between BBR's association with DNA and the function
      of DNA. Here we report that the distribution of BBR within the nucleus can be
      observed 30 minutes after drug administration, and that the content of berberine
      in the nucleus peaks at around 4 umol, which is twelve hours after drug
      administration. The spatial conformation of DNA and chromatin was altered
      immediately after their association with BBR. Moreover, this association can
      effectively suppress the transcription of DNA in living cell systems and cell
      free systems. Electrophoretic mobility shift assays (EMSA) demonstrated further
      that BBR can inhibit the association between the TATA binding protein (TBP) and
      the TATA box in the promoter, and this finding was also attained in living cells
      by chromatin immunoprecipitation (ChIP). Based on results from this study, we
      hypothesize that berberine can suppress the transcription of DNA in living cell
      systems, especially suppressing the association between TBP and the TATA box by
      binding with DNA and, thus, inhibiting TATA box-dependent gene expression in a
      non-specific way. This novel study has significantly expanded the sphere of
      knowledge concerning berberine's pharmacological effects, beginning at its
      paramount initial interaction with the TATA box.

PMID- 21887261
TI  - Age-related immunity to meningococcal serogroup C vaccination: an increase in the
      persistence of IgG2 correlates with a decrease in the avidity of IgG.
AB  - BACKGROUND: All children and adolescents between 1 and 19 years of age in The
      Netherlands received a single meningococcal serogroup C conjugate (MenCC) vaccine
      in 2002. During follow-up 4-5 years later, the persistence of MenC polysaccharide
      specific IgG was found to be dependent on age of vaccination with higher IgG
      levels in the oldest immunized age categories. METHODS AND FINDINGS: Two cross
      sectional population-based serum banks, collected in 1995/1996 and in 2006/2007,
      were used for this study. We measured MenC polysaccharide-specific IgM, the IgG1
      and IgG2 subclasses and determined the avidity of the IgG antibodies. We report
      that the age-related persistence of IgG after immunization with the MenCC vaccine
      seemed to result from an increase of IgG2 levels with age, while IgG1 levels
      remained stable throughout the different age-cohorts. Furthermore, an age-related
      increase in IgM levels was observed, correlating with the persistence of IgG
      antibodies with age. It is noteworthy that the increase in IgG2 correlated with a
      reduced IgG-avidity with age. CONCLUSION: These date indicate that the classical
      characteristics of a T-cell-dependent antibody response as elicited by protein
      based vaccines might not be completely applicable when conjugate vaccines are
      administered to older children and adolescents up to 18 years of age. The
      response elicited by the MenCC vaccine seemed to be more a mixture of both T cell
      dependent and T cell independent responses in terms of humoral immunological
      characteristics.

PMID- 21887262
TI  - Mitotic illegitimate recombination is a mechanism for novel changes in high
      molecular-weight glutenin subunits in wheat-rye hybrids.
AB  - Wide hybrids can have novel traits or changed expression of a quantitative trait
      that their parents do not have. These phenomena have long been noticed, yet the
      mechanisms are poorly understood. High-molecular-weight glutenin subunits (HMW
      GS) are seed storage proteins encoded by Glu-1 genes that only express in
      endosperm in wheat and its related species. Novel HMW-GS compositions have been
      observed in their hybrids. This research elucidated the molecular mechanisms by
      investigating the causative factors of novel HMW-GS changes in wheat-rye hybrids.
      HMW-GS compositions in the endosperm and their coding sequences in the leaves of
      F(1) and F(2) hybrids between wheat landrace Shinchunaga and rye landrace Qinling
      were investigated. Missing and/or additional novel HMW-GSs were observed in the
      endosperm of 0.5% of the 2078 F(1) and 22% of 36 F(2) hybrid seeds. The wildtype
      Glu-1Ax null allele was found to have 42 types of short repeat sequences of 3-60
      bp long that appeared 2 to 100 times. It also has an in-frame stop codon in the
      central repetitive region. Analyzing cloned allele sequences of HMW-GS coding
      gene Glu-1 revealed that deletions involving the in-frame stop codon had
      happened, resulting in novel ~1.8-kb Glu-1Ax alleles in some F(1) and F(2)
      plants. The cloned mutant Glu-1Ax alleles were expressed in Escherichia coli, and
      the HMW-GSs produced matched the novel HMW-GSs found in the hybrids. The
      differential changes between the endosperm and the plant of the same hybrids and
      the data of E. coli expression of the cloned deletion alleles both suggested that
      mitotic illegitimate recombination between two copies of a short repeat sequence
      had resulted in the deletions and thus the changed HMW-GS compositions. Our
      experiments have provided the first direct evidence to show that mitotic
      illegitimate recombination is a mechanism that produces novel phenotypes in wide
      hybrids.

PMID- 21887263
TI  - Molecular mechanism of a green-shifted, pH-dependent red fluorescent protein
      mKate variant.
AB  - Fluorescent proteins that can switch between distinct colors have contributed
      significantly to modern biomedical imaging technologies and molecular cell
      biology. Here we report the identification and biochemical analysis of a green
      shifted red fluorescent protein variant GmKate, produced by the introduction of
      two mutations into mKate. Although the mutations decrease the overall brightness
      of the protein, GmKate is subject to pH-dependent, reversible green-to-red color
      conversion. At physiological pH, GmKate absorbs blue light (445 nm) and emits
      green fluorescence (525 nm). At pH above 9.0, GmKate absorbs 598 nm light and
      emits 646 nm, far-red fluorescence, similar to its sequence homolog mNeptune.
      Based on optical spectra and crystal structures of GmKate in its green and red
      states, the reversible color transition is attributed to the different
      protonation states of the cis-chromophore, an interpretation that was confirmed
      by quantum chemical calculations. Crystal structures reveal potential hydrogen
      bond networks around the chromophore that may facilitate the protonation switch,
      and indicate a molecular basis for the unusual bathochromic shift observed at
      high pH. This study provides mechanistic insights into the color tuning of mKate
      variants, which may aid the development of green-to-red color-convertible
      fluorescent sensors, and suggests GmKate as a prototype of genetically encoded pH
      sensors for biological studies.

PMID- 21887264
TI  - GagCM9-specific CD8+ T cells expressing limited public TCR clonotypes do not
      suppress SIV replication in vivo.
AB  - Several lines of evidence suggest that HIV/SIV-specific CD8(+) T cells play a
      critical role in the control of viral replication. Recently we observed high
      levels of viremia in Indian rhesus macaques vaccinated with a segment of
      SIVmac239 Gag (Gag(45-269)) that were subsequently infected with SIVsmE660. These
      seven Mamu-A*01(+) animals developed CD8(+) T cell responses against an
      immunodominant epitope in Gag, GagCM9, yet failed to control virus replication.
      We carried out a series of immunological and virological assays to understand why
      these Gag-specific CD8(+) T cells could not control virus replication in vivo.
      GagCM9-specific CD8(+) T cells from all of the animals were multifunctional and
      were found in the colonic mucosa. Additionally, GagCM9-specific CD8(+) T cells
      accessed B cell follicles, the primary residence of SIV-infected cells in lymph
      nodes, with effector to target ratios between 20-250 GagCM9-specific CD8(+) T
      cells per SIV-producing cell. Interestingly, vaccinated animals had few public
      TCR clonotypes within the GagCM9-specific CD8(+) T cell population pre- and post
      infection. The number of public TCR clonotypes expressed by GagCM9-specific
      CD8(+) T cells post-infection significantly inversely correlated with chronic
      phase viral load. It is possible that these seven animals failed to control viral
      replication because of the narrow TCR repertoire expressed by the GagCM9-specific
      CD8(+) T cell population elicited by vaccination and infection.

PMID- 21887266
TI  - Evolvable neuronal paths: a novel basis for information and search in the brain.
AB  - We propose a previously unrecognized kind of informational entity in the brain
      that is capable of acting as the basis for unlimited hereditary variation in
      neuronal networks. This unit is a path of activity through a network of neurons,
      analogous to a path taken through a hidden Markov model. To prove in principle
      the capabilities of this new kind of informational substrate, we show how a
      population of paths can be used as the hereditary material for a neuronally
      implemented genetic algorithm, (the swiss-army knife of black-box optimization
      techniques) which we have proposed elsewhere could operate at somatic timescales
      in the brain. We compare this to the same genetic algorithm that uses a standard
      'genetic' informational substrate, i.e. non-overlapping discrete genotypes, on a
      range of optimization problems. A path evolution algorithm (PEA) is defined as
      any algorithm that implements natural selection of paths in a network substrate.
      A PEA is a previously unrecognized type of natural selection that is well suited
      for implementation by biological neuronal networks with structural plasticity.
      The important similarities and differences between a standard genetic algorithm
      and a PEA are considered. Whilst most experiments are conducted on an abstract
      network model, at the conclusion of the paper a slightly more realistic neuronal
      implementation of a PEA is outlined based on Izhikevich spiking neurons. Finally,
      experimental predictions are made for the identification of such informational
      paths in the brain.

PMID- 21887265
TI  - Isolation and characterization of CvIV4: a pain inducing alpha-scorpion toxin.
AB  - BACKGROUND: Among scorpion species, the Buthidae produce the most deadly and
      painful venoms. However, little is known regarding the venom components that
      cause pain and their mechanism of action. Using a paw-licking assay (Mus
      musculus), this study compared the pain-inducing capabilities of venoms from two
      species of New World scorpion (Centruroides vittatus, C. exilicauda) belonging to
      the neurotoxin-producing family Buthidae with one species of non-neurotoxin
      producing scorpion (Vaejovis spinigerus) in the family Vaejovidae. A pain
      inducing alpha-toxin (CvIV4) was isolated from the venom of C. vittatus and
      tested on five Na(+) channel isoforms. PRINCIPAL FINDINGS: C. vittatus and C.
      exilicauda venoms produced significantly more paw licking in Mus than V.
      spinigerus venom. CvIV4 produced paw licking in Mus equivalent to the effects of
      whole venom. CvIV4 slowed the fast inactivation of Na(v)1.7, a Na(+) channel
      expressed in peripheral pain-pathway neurons (nociceptors), but did not affect
      the Na(v)1.8-based sodium currents of these neurons. CvIV4 also slowed the fast
      inactivation of Na(v)1.2, Na(v)1.3 and Na(v)1.4. The effects of CvIV4 are similar
      to Old World alpha-toxins that target Na(v)1.7 (AahII, BmK MI, LqhIII, OD1),
      however the primary structure of CvIV4 is not similar to these toxins. Mutant
      Na(v)1.7 channels (D1586A and E1589Q, DIV S3-S4 linker) reduced but did not
      abolish the effects of CvIV4. CONCLUSIONS: This study: 1) agrees with anecdotal
      evidence suggesting that buthid venom is significantly more painful than non
      neurotoxic venom; 2) demonstrates that New World buthids inflict painful stings
      via toxins that modulate Na(+) channels expressed in nociceptors; 3) reveals that
      Old and New World buthids employ similar mechanisms to produce pain. Old and New
      World alpha-toxins that target Na(v)1.7 have diverged in sequence, but the
      activity of these toxins is similar. Pain-inducing toxins may have evolved in a
      common ancestor. Alternatively, these toxins may be the product of convergent
      evolution.

PMID- 21887267
TI  - Why self-induced pain feels less painful than externally generated pain: distinct
      brain activation patterns in self- and externally generated pain.
AB  - Voluntary movement generally inhibits sensory systems. However, it is not clear
      how such movement influences pain. In the present study, subjects actively or
      passively experienced mechanical pain or pressure during functional MRI scanning.
      Pain and pressure were induced using two modified grip strengthener rings, each
      twined with four crystal bead strings, with polyhedral beads to induce pain, or
      spherical beads to induce pressure. Subjects held one ring in the left hand and
      were either asked to squeeze their left hand with their right hand (i.e., active
      pain or pressure), or to have their left hand squeezed by the experimenter (i.e.,
      passive pain or pressure). Subjects rated the intensity and unpleasantness of the
      pain sensation lower in the active procedure than in the passive one.
      Correspondingly, pain-related brain areas were inhibited in the case of self
      generated pain, including the primary somatosensory cortex (SI), anterior
      cingulate cortex (ACC), and the thalamus. These results suggest that active
      movement behaviorally inhibits concomitant mechanical pain, accompanied by an
      inhibition of pain response in pain-related brain areas such as the SI cortex.
      This might be part of the mechanisms underlying the kinesitherapy for pain
      treatment.

PMID- 21887269
TI  - Stability in and correlation between factors influencing genetic quality of seed
      lots in seed orchard of Pinus tabuliformis Carr. over a 12-year span.
AB  - Coniferous seed orchards require a long period from initial seed harvest to
      stable seed production. Differential reproductive success and asynchrony are
      among the main factors for orchard crops year-to-year variation in terms of
      parental gametic contribution and ultimately the genetic gain. It is fundamental
      in both making predictions about the genetic composition of the seed crop and
      decisions about orchard roguing and improved seed orchard establishment. In this
      paper, a primary Chinese pine seed orchard with 49 clones is investigated for
      stability, variation and correlation analysis of factors which influence genetic
      quality of the seed lots from initial seed harvest to the stable seed production
      over a 12 years span. Results indicated that the reproductive synchrony index of
      pollen shedding has shown to be higher than that of the strobili receptivity, and
      both can be drastically influenced by the ambient climate factors. Reproductive
      synchrony index of the clones has certain relative stability and it could be used
      as an indication of the seed orchard status during maturity stage; clones in the
      studied orchard have shown extreme differences in terms of the gametic and
      genetic contribution to the seed crop at the orchard's early production phase
      specifically when they severe as either female or male parents. Those differences
      are closely related to clonal sex tendency at the time of orchard's initial
      reproduction. Clonal gamete contribution as male and female parent often has a
      negative correlation. Clone utilization as pollen, seed or both pollen and seed
      donors should consider the role it would play in the seed crop; due to numerous
      factors influencing on the mating system in seed orchards, clonal genetic
      contribution as male parent is uncertain, and it has major influence on the
      genetic composition in the seed orchard during the initial reproductive and seed
      production phase.

PMID- 21887268
TI  - Dissecting molecular differences between Wnt coreceptors LRP5 and LRP6.
AB  - Low-density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6) serve
      as Wnt co-receptors for the canonical beta-catenin pathway. While LRP6 is
      essential for embryogenesis, both LRP5 and LRP6 play critical roles for skeletal
      remodeling, osteoporosis pathogenesis and cancer formation, making LRP5 and LRP6
      key therapeutic targets for cancer and disease treatment. LRP5 and LRP6 each
      contain in the cytoplasmic domain five conserved PPPSPxS motifs that are pivotal
      for signaling and serve collectively as phosphorylation-dependent docking sites
      for the scaffolding protein Axin. However existing data suggest that LRP6 is more
      effective than LRP5 in transducing the Wnt signal. To understand the molecular
      basis that accounts for the different signaling activity of LRP5 and LRP6, we
      generated a series of chimeric receptors via swapping LRP5 and LRP6 cytoplasmic
      domains, LRP5C and LRP6C, and studied their Wnt signaling activity using
      biochemical and functional assays. We demonstrate that LRP6C exhibits strong
      signaling activity while LRP5C is much less active in cells. Recombinant LRP5C
      and LRP6C upon in vitro phosphorylation exhibit similar Axin-binding capability,
      suggesting that LRP5 and LRP6 differ in vivo at a step prior to Axin-binding,
      likely at receiving phosphorylation. We identified between the two most carboxyl
      PPPSPxS motifs an intervening "gap4" region that appears to account for much of
      the difference between LRP5C and LRP6C, and showed that alterations in this
      region are sufficient to enhance LRP5 PPPSPxS phosphorylation and signaling to
      levels comparable to LRP6 in cells. In addition we provide evidence that binding
      of phosphorylated LRP5 or LRP6 to Axin is likely direct and does not require the
      GSK3 kinase as a bridging intermediate as has been proposed. Our studies
      therefore uncover a new and important molecular tuning mechanism for differential
      regulation of LRP5 and LRP6 phosphorylation and signaling activity.

PMID- 21887270
TI  - Symbiotic effectiveness of rhizobial mutualists varies in interactions with
      native Australian legume genera.
AB  - BACKGROUND AND OBJECTIVES: Interactions between plants and beneficial soil
      organisms (e.g. rhizobial bacteria, mycorrhizal fungi) are models for
      investigating the ecological impacts of such associations in plant communities,
      and the evolution and maintenance of variation in mutualisms (e.g. host
      specificity and the level of benefits provided). With relatively few exceptions,
      variation in symbiotic effectiveness across wild host species is largely
      unexplored. METHODS: We evaluated these associations using representatives of
      several legume genera which commonly co-occur in natural ecosystems in south
      eastern Australia and an extensive set of rhizobial strains isolated from these
      hosts. These strains had been previously assigned to specific phylotypes on the
      basis of molecular analyses. In the first of two inoculation experiments, the
      growth responses of each host species was evaluated with rhizobial strains
      isolated from that species. The second experiment assessed performance across
      genera and the extent of host specificity using a subset of these strains.
      RESULTS: While host growth responses to their own (sympatric) isolates varied
      considerably, rhizobial phylotype was a significant predictor of symbiotic
      performance, indicating that bacterial species designations on the basis of
      molecular markers have ecological importance. Hosts responded in qualitatively
      different ways to sympatric and allopatric strains of rhizobia, ranging from
      species with a clear preference for their own strains, to those that were broad
      generalists, through to species that grew significantly better with allopatric
      strains. CONCLUSION: Theory has focused on trade-offs between the provision of
      benefits and symbiont competitive ability that might explain the persistence of
      less beneficial strains. However, differences in performance among co-occurring
      host species could also drive such patterns. Our results thus highlight the
      likely importance of plant community structure in maintaining variation in
      symbiotic effectiveness.

PMID- 21887271
TI  - Novel cellulose-binding-domain protein in Phytophthora is cell wall localized.
AB  - Cellulose binding domains (CBD) in the carbohydrate binding module family 1
      (CBM1) are structurally conserved regions generally linked to catalytic regions
      of cellulolytic enzymes. While widespread amongst saprophytic fungi that subsist
      on plant cell wall polysaccharides, they are absent amongst most plant pathogenic
      fungal cellulases. A genome wide survey for CBM1 was performed on the highly
      destructive plant pathogen Phytophthora infestans, a fungal-like Stramenopile, to
      determine if it harbored cellulolytic enzymes with CBM1. Only five genes were
      found to encode CBM1, and none were associated with catalytic domains. Surveys of
      other genomes indicated that the CBM1-containing proteins, lacking other domains,
      represent a unique group of proteins largely confined to the Stramenopiles.
      Immunolocalization of one of these proteins, CBD1, indicated that it is embedded
      in the hyphal cell wall. Proteins with CBM1 domains can have plant host elicitor
      activity, but tests with Agrobacterium-mediated in planta expression and
      synthetic peptide infiltration failed to identify plant hypersensitive
      elicitation with CBD1. A structural basis for differential elicitor activity is
      proposed.

PMID- 21887272
TI  - In-cell NMR in E. coli to monitor maturation steps of hSOD1.
AB  - In-cell NMR allows characterizing the folding state of a protein as well as
      posttranslational events at molecular level, in the cellular context. Here, the
      initial maturation steps of human copper, zinc superoxide dismutase 1 are
      characterized in the E. coli cytoplasm by in-cell NMR: from the apo protein,
      which is partially unfolded, to the zinc binding which causes its final
      quaternary structure. The protein selectively binds only one zinc ion, whereas in
      vitro also the copper site binds a non-physiological zinc ion. However, no
      intramolecular disulfide bridge formation occurs, nor copper uptake, suggesting
      the need of a specific chaperone for those purposes.

PMID- 21887273
TI  - Identification of novel biomarkers in seasonal allergic rhinitis by combining
      proteomic, multivariate and pathway analysis.
AB  - BACKGROUND: Glucocorticoids (GCs) play a key role in the treatment of seasonal
      allergic rhinitis (SAR). However, some patients show a low response to GC
      treatment. We hypothesized that proteins that correlated to discrimination
      between symptomatic high and low responders (HR and LR) to GC treatment might be
      regulated by GCs and therefore suitable as biomarkers for GC treatment.
      METHODOLOGY/PRINCIPAL FINDINGS: We identified 953 nasal fluid proteins in
      symptomatic HR and LR with a LC MS/MS based-quantitative proteomics analysis and
      performed multivariate analysis to identify a combination of proteins that best
      separated symptomatic HR and LR. Pathway analysis showed that those proteins were
      most enriched in the acute phase response pathway. We prioritized candidate
      biomarkers for GC treatment based on the multivariate and pathway analysis. Next,
      we tested if those candidate biomarkers differed before and after GC treatment in
      nasal fluids from 40 patients with SAR using ELISA. Several proteins including
      ORM (P<0.0001), APOH (P<0.0001), FGA (P<0.01), CTSD (P<0.05) and SERPINB3
      (P<0.05) differed significantly before and after GC treatment. Particularly, ORM
      (P<0.01), FGA (P<0.05) and APOH (P<0.01) that belonged to the acute phase
      response pathway decreased significantly in HR but not LR before and after GC
      treatment. CONCLUSIONS/SIGNIFICANCE: We identified several novel biomarkers for
      GC treatment response in SAR with combined proteomics, multivariate and pathway
      analysis. The analytical principles may be generally applicable to identify
      biomarkers in clinical studies of complex diseases.

PMID- 21887274
TI  - Albiglutide, a long lasting glucagon-like peptide-1 analog, protects the rat
      heart against ischemia/reperfusion injury: evidence for improving cardiac
      metabolic efficiency.
AB  - BACKGROUND: The cardioprotective effects of glucagon-like peptide-1 (GLP-1) and
      analogs have been previously reported. We tested the hypothesis that albiglutide,
      a novel long half-life analog of GLP-1, may protect the heart against I/R injury
      by increasing carbohydrate utilization and improving cardiac energetic
      efficiency. METHODS/PRINCIPAL FINDINGS: Sprague-Dawley rats were treated with
      albiglutide and subjected to 30 min myocardial ischemia followed by 24 h
      reperfusion. Left ventricle infarct size, hemodynamics, function and energetics
      were determined. In addition, cardiac glucose disposal, carbohydrate metabolism
      and metabolic gene expression were assessed. Albiglutide significantly reduced
      infarct size and concomitantly improved post-ischemic hemodynamics, cardiac
      function and energetic parameters. Albiglutide markedly increased both in vivo
      and ex vivo cardiac glucose uptake while reducing lactate efflux. Analysis of
      metabolic substrate utilization directly in the heart showed that albiglutide
      increased the relative carbohydrate versus fat oxidation which in part was due to
      an increase in both glucose and lactate oxidation. Metabolic gene expression
      analysis indicated upregulation of key glucose metabolism genes in the non
      ischemic myocardium by albiglutide. CONCLUSION/SIGNIFICANCE: Albiglutide reduced
      myocardial infarct size and improved cardiac function and energetics following
      myocardial I/R injury. The observed benefits were associated with enhanced
      myocardial glucose uptake and a shift toward a more energetically favorable
      substrate metabolism by increasing both glucose and lactate oxidation. These
      findings suggest that albiglutide may have direct therapeutic potential for
      improving cardiac energetics and function.

PMID- 21887275
TI  - Insulin receptor tyrosine kinase substrate enhances low levels of MDM2-mediated
      p53 ubiquitination.
AB  - The tumor suppressor p53 controls multiple cellular functions including DNA
      repair, cell cycle arrest and apoptosis. MDM2-mediated p53 ubiquitination affects
      both degradation and cytoplasmic localization of p53. Several cofactors are known
      to modulate MDM2-mediated p53 ubiquitination and proteasomal degradation. Here we
      show that IRTKS, a novel IRSp53-like protein inhibited p53-induced apoptosis and
      depressed its transcription activity. IRTKS bound directly to p53 and increased
      p53 ubiquitination and cytoplasmic localization. Further studies revealed that
      IRTKS interacted with MDM2 and promoted low levels of MDM2-mediated p53
      ubiquitination in vitro and in vivo. In unstressed cells with low levels of MDM2,
      IRTKS was found to stabilize the interaction of p53 and MDM2. In stressed cells,
      IRTKS dissociated from p53, and high levels of MDM2 induced by p53 activation
      mediate IRTKS poly-ubiquitination and subsequent proteasomal degradation. These
      data suggest that IRTKS is a novel regulator of p53, modulating low level of MDM2
      mediated p53 ubiquitination in unstressed cells.

PMID- 21887276
TI  - CK2 phosphorylation of Schistosoma mansoni HMGB1 protein regulates its cellular
      traffic and secretion but not its DNA transactions.
AB  - BACKGROUND: The helminth Schistosoma mansoni parasite resides in mesenteric veins
      where fecundated female worms lay hundred of eggs daily. Some of the egg antigens
      are trapped in the liver and induce a vigorous granulomatous response. High
      Mobility Group Box 1 (HMGB1), a nuclear factor, can also be secreted and act as a
      cytokine. Schistosome HMGB1 (SmHMGB1) is secreted by the eggs and stimulate the
      production of key cytokines involved in the pathology of schistosomiasis. Thus,
      understanding the mechanism of SmHMGB1 release becomes mandatory. Here, we
      addressed the question of how the nuclear SmHMGB1 can reach the extracellular
      space. PRINCIPAL FINDINGS: We showed in vitro and in vivo that CK2
      phosphorylation was involved in the nucleocytoplasmic shuttling of SmHMGB1. By
      site-directed mutagenesis we mapped the two serine residues of SmHMGB1 that were
      phosphorylated by CK2. By DNA bending and supercoiling assays we showed that CK2
      phosphorylation of SmHMGB1 had no effect in the DNA binding activities of the
      protein. We showed by electron microscopy, as well as by cell transfection and
      fluorescence microscopy that SmHMGB1 was present in the nucleus and cytoplasm of
      adult schistosomes and mammalian cells. In addition, we showed that treatments of
      the cells with either a phosphatase or a CK2 inhibitor were able to enhance or
      block, respectively, the cellular traffic of SmHMGB1. Importantly, we showed by
      confocal microscopy and biochemically that SmHMGB1 is significantly secreted by
      S. mansoni eggs of infected animals and that SmHMGB1 that were localized in the
      periovular schistosomotic granuloma were phosphorylated. CONCLUSIONS: We showed
      that secretion of SmHMGB1 is regulated by phosphorylation. Moreover, our results
      suggest that egg-secreted SmHMGB1 may represent a new egg antigen. Therefore, the
      identification of drugs that specifically target phosphorylation of SmHMGB1 might
      block its secretion and interfere with the pathogenesis of schistosomiasis.

PMID- 21887277
TI  - Serum-nutrient starvation induces cell death mediated by Bax and Puma that is
      counteracted by p21 and unmasked by Bcl-x(L) inhibition.
AB  - The cyclin-dependent kinase inhibitor p21 (p21WAF1/Cip1) is a multifunctional
      protein known to promote cell cycle arrest and survival in response to p53
      dependent and p53 independent stimuli. We herein investigated whether and how it
      might contribute to the survival of cancer cells that are in low-nutrient
      conditions during tumour growth, by culturing isogenic human colorectal cancer
      cell lines (HCT116) and breast cancer cell lines in a medium deprived in amino
      acids and serum. We show that such starvation enhances, independently from p53,
      the expression of p21 and that of the pro-apoptotic BH3-only protein Puma. Under
      these conditions, p21 prevents Puma and its downstream effector Bax from
      triggering the mitochondrial apoptotic pathway. This anti-apoptotic effect is
      exerted from the cytosol but it is unrelated to the ability of p21 to interfere
      with the effector caspase 3. The survival function of p21 is, however, overcome
      by RNA interference mediated Bcl-x(L) depletion, or by the pharmacological
      inhibitor ABT-737. Thus, an insufficient supply in nutrients may not have an
      overt effect on cancer cell viability due to p21 induction, but it primes these
      cells to die, and sensitizes them to the deleterious effects of Bcl-x(L)
      inhibitors regardless of their p53 status.

PMID- 21887278
TI  - Spatial association of signaling proteins and F-actin effects on cluster assembly
      analyzed via photoactivation localization microscopy in T cells.
AB  - Recognition of antigens by T cell receptors (TCRs) triggers cellular signaling
      cascades initiated by recruitment to the plasma membrane of numerous effector
      molecules to form signaling microclusters (MCs). Here we show that the method of
      high-resolution photoactivation localization microscopy (PALM) imaging can be
      used to analyze the spatial correlation between kinase ZAP70 and adaptor SLP76
      MCs at the cell periphery and the effects of F-actin on MC assembly. We first
      determined the photophysical rate constants of Dronpa and tdEos fluorescence
      probes, which allowed us to optimize our dual-color PALM imaging method. We next
      analyzed the degrees of spatial association through determination of Mander's
      colocalization coefficients from PALM images, which revealed increasing spatial
      segregation of ZAP70 and SLP76 MCs at the cell periphery after initiation of
      signaling. We showed that this spatial segregation at the cell periphery occurred
      in parallel with the reduction of MC phosphorylation levels. Furthermore, we used
      Ripley's K function to analyze spatial randomness, and determined average radii
      of clusters as a function of activation time. The average radii of SLP76 and LAT
      MCs were found to decrease, whereas ZAP70 MC radii remained relatively constant.
      Finally, effects of F-actin depolymerization on MC morphology were studied by
      determining radial distributions of cluster circularity. Our data suggest that MC
      morphology is affected by actin polymerization. The quantitative analysis of sub
      diffraction PALM images may provide a starting point for a molecular
      interpretation of cluster-cluster interactions and of the regulation of T cell
      signaling MCs by the cytoskeleton.

PMID- 21887279
TI  - Cell culture replication of a genotype 1b hepatitis C virus isolate cloned from a
      patient who underwent liver transplantation.
AB  - The introduction of the genotype 2a isolate JFH1 was a major breakthrough in the
      field of hepatitis C virus (HCV), allowing researchers to study the complete life
      cycle of the virus in cell culture. However, fully competent culture systems
      encompassing the most therapeutically relevant HCV genotypes are still lacking,
      especially for the highly drug-resistant genotype 1b. For most isolated HCV
      clones, efficient replication in cultured hepatoma cells requires the
      introduction of replication-enhancing mutations. However, such mutations may
      interfere with viral assembly, as occurs in the case of the genotype 1b isolate
      Con1. In this study, we show that a clinical serum carrying a genotype 1b virus
      with an exceptionally high viral load was able to infect Huh7.5 cells. Similar to
      previous reports, inoculation of Huh7.5 cells by natural virus is very
      inefficient compared to infection by cell culture HCV. A consensus sequence of a
      new genotype 1b HCV isolate was cloned from the clinical serum (designated
      Barcelona HCV1), and then subjected to replication studies. This virus replicated
      poorly in a transient fashion in Huh7.5 cells after electroporation with in vitro
      transcribed RNA. Nonetheless, approximately 3 weeks post electroporation and
      thereafter, core protein-positive cells were detected by immunofluorescence.
      Surprisingly, small amounts of core protein were also measurable in the
      supernatant of electroporated cells, suggesting that HCV particles might be
      assembled and released. Our findings not only enhance the current method of
      cloning in vitro HCV replication-competent isolates, but also offer valuable
      insights for the realization of fully competent culture systems for HCV.

PMID- 21887280
TI  - High density lipoprotein structural changes and drug response in lipidomic
      profiles following the long-term fenofibrate therapy in the FIELD substudy.
AB  - In a recent FIELD study the fenofibrate therapy surprisingly failed to achieve
      significant benefit over placebo in the primary endpoint of coronary heart
      disease events. Increased levels of atherogenic homocysteine were observed in
      some patients assigned to fenofibrate therapy but the molecular mechanisms behind
      this are poorly understood. Herein we investigated HDL lipidomic profiles
      associated with fenofibrate treatment and the drug-induced Hcy levels in the
      FIELD substudy. We found that fenofibrate leads to complex HDL compositional
      changes including increased apoA-II, diminishment of lysophosphatidylcholines and
      increase of sphingomyelins. Ethanolamine plasmalogens were diminished only in a
      subgroup of fenofibrate-treated patients with elevated homocysteine levels.
      Finally we performed molecular dynamics simulations to qualitatively reconstitute
      HDL particles in silico. We found that increased number of apoA-II excludes
      neutral lipids from HDL surface and apoA-II is more deeply buried in the lipid
      matrix than apoA-I. In conclusion, a detailed molecular characterization of HDL
      may provide surrogates for predictors of drug response and thus help identify the
      patients who might benefit from fenofibrate treatment.

PMID- 21887281
TI  - The transcriptome of Trichuris suis--first molecular insights into a parasite
      with curative properties for key immune diseases of humans.
AB  - BACKGROUND: Iatrogenic infection of humans with Trichuris suis (a parasitic
      nematode of swine) is being evaluated or promoted as a biological, curative
      treatment of immune diseases, such as inflammatory bowel disease (IBD) and
      ulcerative colitis, in humans. Although it is understood that short-term T. suis
      infection in people with such diseases usually induces a modified Th2-immune
      response, nothing is known about the molecules in the parasite that induce this
      response. METHODOLOGY/PRINCIPAL FINDINGS: As a first step toward filling the gaps
      in our knowledge of the molecular biology of T. suis, we characterised the
      transcriptome of the adult stage of this nematode employing next-generation
      sequencing and bioinformatic techniques. A total of ~65,000,000 reads were
      generated and assembled into ~20,000 contiguous sequences ( = contigs); ~17,000
      peptides were predicted and classified based on homology searches, protein motifs
      and gene ontology and biological pathway mapping. CONCLUSIONS: These analyses
      provided interesting insights into a number of molecular groups, particularly
      predicted excreted/secreted molecules (n = 1,288), likely to be involved in the
      parasite-host interactions, and also various molecules (n = 120) linked to
      chemokine, T-cell receptor and TGF-beta signalling as well as leukocyte
      transendothelial migration and natural killer cell-mediated cytotoxicity, which
      are likely to be immuno-regulatory or -modulatory in the infected host. This
      information provides a conceptual framework within which to test the
      immunobiological basis for the curative effect of T. suis infection in humans
      against some immune diseases. Importantly, the T. suis transcriptome
      characterised herein provides a curated resource for detailed studies of the
      immuno-molecular biology of this parasite, and will underpin future genomic and
      proteomic explorations.

PMID- 21887282
TI  - A novel immunodominant CD8+ T cell response restricted by a common HLA-C allele
      targets a conserved region of Gag HIV-1 clade CRF01_AE infected Thais.
AB  - BACKGROUND: CD8+ T cell responses play an important role in the control of HIV-1.
      The extensive sequence diversity of HIV-1 represents a critical hurdle to
      developing an effective HIV-1 vaccine, and it is likely that regional-specific
      vaccine strains will be required to overcome the diversity of the different HIV-1
      clades distributed world-wide. Unfortunately, little is known about the CD8+ T
      cell responses against CRF01_AE, which is responsible for the majority of
      infections in Southeast Asia. METHODOLOGY/PRINCIPAL FINDINGS: To identify
      dominant CD8+ T cell responses recognized in HIV-1 clade CRF01_AE infected
      subjects we drew upon data from an immunological screen of 100 HIV-1 clade
      CRF01_AE infected subjects using IFN-gamma ELISpot to characterize a novel
      immunodominant CD8+ T cell response in HIV-1 Gag restricted by HLA-Cw*0102 (p24,
      (277)YSPVSILDI(285), YI9). Over 75% of Cw*0102+ve subjects targeted this epitope,
      representing the strongest response in more than a third of these individuals.
      This novel CD8 epitope was located in a highly conserved region of HIV-1 Gag
      known to contain immunodominant CD8 epitopes, which are restricted by HLA-B*57
      and -B*27 in clade B infection. Nonetheless, viral escape in this epitope was
      frequently observed in Cw*0102+ve subjects, suggestive of strong selection
      pressure being exerted by this common CD8+ T cell response.
      CONCLUSIONS/SIGNIFICANCE: As HLA-Cw*0102 is frequently expressed in the Thai
      population (allelic frequency of 16.8%), this immunodominant Cw*0102-restricted
      Gag epitope may represent an attractive candidate for vaccines specific to
      CRF01_AE and may help facilitate further studies of immunopathogenesis in this
      understudied HIV-1 clade.

PMID- 21887283
TI  - Molecular basis of NDM-1, a new antibiotic resistance determinant.
AB  - The New Delhi Metallo-beta-lactamase (NDM-1) was first reported in 2009 in a
      Swedish patient. A recent study reported that Klebsiella pneumonia NDM-1 positive
      strain or Escherichia coli NDM-1 positive strain was highly resistant to all
      antibiotics tested except tigecycline and colistin. These can no longer be relied
      on to treat infections and therefore, NDM-1 now becomes potentially a major
      global health threat.In this study, we performed modeling studies to obtain its
      3D structure and NDM-1/antibiotics complex. It revealed that the hydrolytic
      mechanisms are highly conserved. In addition, the detailed analysis indicates
      that the more flexible and hydrophobic loop1, together with the evolution of more
      positive-charged loop2 leads to NDM-1 positive strain more potent and extensive
      in antibiotics resistance compared with other MBLs. Furthermore, through
      biological experiments, we revealed the molecular basis for antibiotics catalysis
      of NDM-1 on the enzymatic level. We found that NDM-1 enzyme was highly potent to
      degrade carbapenem antibiotics, while mostly susceptible to tigecycline, which
      had the ability to slow down the hydrolysis velocity of meropenem by NDM-1.
      Meanwhile, the mutagenesis experiments, including D124A, C208A, K211A and K211E,
      which displayed down-regulation on meropenem catalysis, proved the accuracy of
      our model.At present, there are no effective antibiotics against NDM-1 positive
      pathogen. Our study will provide clues to investigate the molecular basis of
      extended antibiotics resistance of NDM-1 and then accelerate the search for new
      antibiotics against NDM-1 positive strain in clinical studies.

PMID- 21887284
TI  - Pharmacogenetic associations of MMP9 and MMP12 variants with cardiovascular
      disease in patients with hypertension.
AB  - OBJECTIVES: MMP-9 and -12 function in tissue remodeling and may play roles in
      cardiovascular disease (CVD). We assessed associations of four MMP polymorphisms
      and three antihypertensive drugs with cardiovascular outcomes. METHODS:
      Hypertensives (n = 42,418) from a double-blind, randomized, clinical trial were
      randomized to chlorthalidone, amlodipine, lisinopril, or doxazosin treatment
      (mean follow up, 4.9 years). The primary outcome was coronary heart disease
      (CHD). Secondary outcomes included combined CHD, all CVD outcomes combined,
      stroke, heart failure (HF), and mortality. Genotype-treatment interactions were
      tested. RESULTS: There were 38,698 participants genotyped for at least one of the
      polymorphisms included here. For MMP9 R668Q (rs2274756), lower hazard ratios
      (HRs) were found for AA subjects for most outcomes when treated with
      chlorthalidone versus amlodipine (eg., CCHD: GG = 1.00, GA = 1.01, AA = 0.64; P =
      0.038). For MMP9 R279Q (rs17576), modest pharmacogenetic findings were observed
      for combined CHD and the composite CVD outcome. For MMP12 N122S (rs652438), lower
      HRs were observed for CHD in subjects carrying at least one G allele and being
      treated with chlorthalidone versus lisinopril (CHD: AA = 1.07, AG = 0.80, GG =
      0.49; P = 0.005). In the lisinopril-amlodipine comparison, higher HRs were
      observed for participants having at least one G allele at the MMP12 N122S locus
      (CHD: AA = 0.94, AG = 1.19, GG = 1.93; P = 0.041). For MMP12 -82A>G (rs2276109),
      no pharmacogenetic effect was found for the primary outcome, although lower HRs
      were observed for AA homozygotes in the chlorthalidone-amlodipine comparison for
      HF (P = 0.015). CONCLUSIONS: We observed interactions between antihypertensive
      drugs and MMP9 and MMP12 for CHD and composite CVD. The data suggest that these
      genes may provide useful clinical information with respect to treatment
      decisions.

PMID- 21887285
TI  - Prediction of peptide reactivity with human IVIg through a knowledge-based
      approach.
AB  - The prediction of antibody-protein (antigen) interactions is very difficult due
      to the huge variability that characterizes the structure of the antibodies. The
      region of the antigen bound to the antibodies is called epitope. Experimental
      data indicate that many antibodies react with a panel of distinct epitopes
      (positive reaction). The Challenge 1 of DREAM5 aims at understanding whether
      there exists rules for predicting the reactivity of a peptide/epitope, i.e., its
      capability to bind to human antibodies. DREAM 5 provided a training set of
      peptides with experimentally identified high and low reactivities to human
      antibodies. On the basis of this training set, the participants to the challenge
      were asked to develop a predictive model of reactivity. A test set was then
      provided to evaluate the performance of the model implemented so far.We developed
      a logistic regression model to predict the peptide reactivity, by facing the
      challenge as a machine learning problem. The initial features have been generated
      on the basis of the available knowledge and the information reported in the
      dataset. Our predictive model had the second best performance of the challenge.
      We also developed a method, based on a clustering approach, able to "in-silico"
      generate a list of positive and negative new peptide sequences, as requested by
      the DREAM5 "bonus round" additional challenge.The paper describes the developed
      model and its results in terms of reactivity prediction, and highlights some open
      issues concerning the propensity of a peptide to react with human antibodies.

PMID- 21887286
TI  - Do Pere David's deer lose memories of their ancestral predators?
AB  - Whether prey retains antipredator behavior after a long period of predator
      relaxation is an important question in predator-prey evolution. Pere David's deer
      have been raised in enclosures for more than 1200 years and this isolation
      provides an opportunity to study whether Pere David's deer still respond to the
      cues of their ancestral predators or to novel predators. We played back the
      sounds of crows (familiar sound) and domestic dogs (familiar non-predators), of
      tigers and wolves (ancestral predators), and of lions (potential naive predator)
      to Pere David's deer in paddocks, and blank sounds to the control group, and
      videoed the behavior of the deer during the experiment. We also showed life-size
      photo models of dog, leopard, bear, tiger, wolf, and lion to the deer and video
      taped their responses after seeing these models. Pere David's deer stared at and
      approached the hidden loudspeaker when they heard the roars of tiger or lion. The
      deer listened to tiger roars longer, approached to tiger roars more and spent
      more time staring at the tiger model. The stags were also found to forage less in
      the trials of tiger roars than that of other sound playbacks. Additionally, it
      took longer for the deer to restore their normal behavior after they heard tiger
      roars, which was longer than that after the trial of other sound playbacks.
      Moreover, the deer were only found to walk away after hearing the sounds of tiger
      and wolf. Therefore, the tiger was probably the main predator for Pere David's
      deer in ancient time. Our study implies that Pere David's deer still retain the
      memories of the acoustic and visual cues of their ancestral predators in spite of
      the long term isolation from natural habitat.

PMID- 21887287
TI  - The GC-rich mitochondrial and plastid genomes of the green alga Coccomyxa give
      insight into the evolution of organelle DNA nucleotide landscape.
AB  - Most of the available mitochondrial and plastid genome sequences are biased
      towards adenine and thymine (AT) over guanine and cytosine (GC). Examples of GC
      rich organelle DNAs are limited to a small but eclectic list of species,
      including certain green algae. Here, to gain insight in the evolution of
      organelle nucleotide landscape, we present the GC-rich mitochondrial and plastid
      DNAs from the trebouxiophyte green alga Coccomyxa sp. C-169. We compare these
      sequences with other GC-rich organelle DNAs and argue that the forces biasing
      them towards G and C are nonadaptive and linked to the metabolic and/or life
      history features of this species. The Coccomyxa organelle genomes are also used
      for phylogenetic analyses, which highlight the complexities in trying to resolve
      the interrelationships among the core chlorophyte green algae, but ultimately
      favour a sister relationship between the Ulvophyceae and Chlorophyceae, with the
      Trebouxiophyceae branching at the base of the chlorophyte crown.

PMID- 21887288
TI  - Urothelial plaque formation in post-Golgi compartments.
AB  - Urothelial plaques are specialized membrane domains in urothelial superficial
      (umbrella) cells, composed of highly ordered uroplakin particles. We investigated
      membrane compartments involved in the formation of urothelial plaques in mouse
      umbrella cells. The Golgi apparatus did not contain uroplakins organized into
      plaques. In the post-Golgi region, three distinct membrane compartments
      containing uroplakins were characterized: i) Small rounded vesicles, located
      close to the Golgi apparatus, were labelled weakly with anti-uroplakin antibodies
      and they possessed no plaques; we termed them "uroplakin-positive transporting
      vesicles" (UPTVs). ii) Spherical-to-flattened vesicles, termed "immature fusiform
      vesicles" (iFVs), were uroplakin-positive in their central regions and contained
      small urothelial plaques. iii) Flattened "mature fusiform vesicles" (mFVs)
      contained large plaques, which were densely labelled with anti-uroplakin
      antibodies. Endoytotic marker horseradish peroxidase was not found in these post
      Golgi compartments. We propose a detailed model of de novo urothelial plaque
      formation in post-Golgi compartments: UPTVs carrying individual 16-nm particles
      detach from the Golgi apparatus and subsequently fuse into iFV. Concentration of
      16-nm particles into plaques and removal of uroplakin-negative membranes takes
      place in iFVs. With additional fusions and buddings, iFVs mature into mFVs, each
      carrying two urothelial plaques toward the apical surface of the umbrella cell.

PMID- 21887289
TI  - Glucose-raising genetic variants in MADD and ADCY5 impair conversion of
      proinsulin to insulin.
AB  - INTRODUCTION: Recent meta-analyses of genome-wide association studies revealed
      new genetic loci associated with fasting glycemia. For several of these loci, the
      mechanism of action in glucose homeostasis is unclear. The objective of the study
      was to establish metabolic phenotypes for these genetic variants to deliver clues
      to their pathomechanism. METHODS: In this cross-sectional study 1782 non-diabetic
      volunteers at increased risk for type 2 diabetes underwent an oral glucose
      tolerance test. Insulin, C-peptide and proinsulin were measured and genotyping
      was performed for 12 single nucleotide polymorphisms (SNP) in or near the genes
      GCK (rs4607517), DGKB (rs2191349), GCKR (rs780094), ADCY5 (rs11708067), MADD
      (rs7944584), ADRA2A (rs10885122), FADS1 (rs174550), CRY2 (rs11605924), SLC2A2
      (rs11920090), PROX1 (rs340874), GLIS3 (rs7034200) and C2CD4B (rs11071657).
      Parameters of insulin secretion (AUC Insulin(0-30)/AUC Glucose(0-30), AUC C
      peptide(0-120)/AUC Glucose(0-120)), proinsulin-to-insulin conversion (fasting
      proinsulin, fasting proinsulin/insulin, AUC Proinsulin(0-120)/AUCInsulin(0-120))
      and insulin resistance (HOMA-IR, Matsuda-Index) were assessed. RESULTS: After
      adjustment for confounding variables, the effect alleles of the ADCY5 and MADD
      SNPs were associated with an impaired proinsulin-to-insulin conversion (p = 0.002
      and p = 0.0001, respectively). GLIS3 was nominally associated with impaired
      proinsulin-to-insulin conversion and insulin secretion. The diabetogenic alleles
      of DGKB and PROX1 were nominally associated with reduced insulin secretion.
      Nominally significant effects on insulin sensitivity could be found for MADD and
      PROX1. DISCUSSION: By examining parameters of glucose-stimulated proinsulin-to
      insulin conversion during an OGTT, we show that the SNP in ADCY5 is implicated in
      defective proinsulin-to-insulin conversion. In addition, we confirmed previous
      findings on the role of a genetic variant in MADD on proinsulin-to-insulin
      conversion. These effects may also be related to neighboring regions of the
      genome.

PMID- 21887290
TI  - Rectification of the water permeability in COS-7 cells at 22, 10 and 0 degrees C.
AB  - The osmotic and permeability parameters of a cell membrane are essential physico
      chemical properties of a cell and particularly important with respect to cell
      volume changes and the regulation thereof. Here, we report the hydraulic
      conductivity, L(p), the non-osmotic volume, V(b), and the Arrhenius activation
      energy, E(a), of mammalian COS-7 cells. The ratio of V(b) to the isotonic cell
      volume, V(c iso), was 0.29. E(a), the activation energy required for the
      permeation of water through the cell membrane, was 10,700, and 12,000 cal/mol
      under hyper- and hypotonic conditions, respectively. Average values for L(p) were
      calculated from swell/shrink curves by using an integrated equation for L(p). The
      curves represented the volume changes of 358 individually measured cells, placed
      into solutions of nonpermeating solutes of 157 or 602 mOsm/kg (at 0, 10 or 22
      degrees C) and imaged over time. L(p) estimates for all six combinations of
      osmolality and temperature were calculated, resulting in values of 0.11, 0.21,
      and 0.10 um/min/atm for exosmotic flow and 0.79, 1.73 and 1.87 um/min/atm for
      endosmotic flow (at 0, 10 and 22 degrees C, respectively). The unexpected finding
      of several fold higher L(p) values for endosmotic flow indicates highly
      asymmetric membrane permeability for water in COS-7. This phenomenon is known as
      rectification and has mainly been reported for plant cell, but only rarely for
      animal cells. Although the mechanism underlying the strong rectification found in
      COS-7 cells is yet unknown, it is a phenomenon of biological interest and has
      important practical consequences, for instance, in the development of optimal
      cryopreservation.

PMID- 21887292
TI  - The impact of socio-demographic and religious factors upon sexual behavior among
      Ugandan university students.
AB  - INTRODUCTION: More knowledge is needed about structural factors in society that
      affect risky sexual behaviors. Educational institutions such as universities
      provide an opportune arena for interventions among young people. The aim of this
      study was to investigate the relationship between sociodemographic and religious
      factors and their impact on sexual behavior among university students in Uganda.
      METHODS: In 2005, 980 university students (response rate 80%) were assessed by a
      self-administered questionnaire. Validated instruments were used to assess socio
      demographic and religious factors and sexual behavior. Logistic regression
      analyses were applied. RESULTS: Our findings indicated that 37% of the male and
      49% of the female students had not previously had sex. Of those with sexual
      experience, 46% of the males and 23% of the females had had three or more sexual
      partners, and 32% of the males and 38% of the females did not consistently use
      condoms. For those who rated religion as less important in their family, the
      probability of early sexual activity and having had a high number of lifetime
      partners increased by a statistically significant amount (OR = 1.7; 95% CI: 1.2
      2.4 and OR = 1.6; 95% CI: 1.1-2.3, respectively). However, the role of religion
      seemed to have no impact on condom use. Being of Protestant faith interacted with
      gender: among those who had debuted sexually, Protestant female students were
      more likely to have had three or more lifetime partners; the opposite was true
      for Protestant male students. CONCLUSION: Religion emerged as an important
      determinant of sexual behavior among Ugandan university students. Our findings
      correlate with the increasing number of conservative religious injunctions
      against premarital sex directed at young people in many countries with a high
      burden. of HIV/AIDS. Such influence of religion must be taken into account in
      order to gain a deeper understanding of the forces that shape sexual behavior in
      Uganda.

PMID- 21887291
TI  - GABAergic neuron deficit as an idiopathic generalized epilepsy mechanism: the
      role of BRD2 haploinsufficiency in juvenile myoclonic epilepsy.
AB  - Idiopathic generalized epilepsy (IGE) syndromes represent about 30% of all
      epilepsies. They have strong, but elusive, genetic components and sex-specific
      seizure expression. Multiple linkage and population association studies have
      connected the bromodomain-containing gene BRD2 to forms of IGE. In mice, a null
      mutation at the homologous Brd2 locus results in embryonic lethality while
      heterozygous Brd2+/- mice are viable and overtly normal. However, using the
      flurothyl model, we now show, that compared to the Brd2+/+ littermates, Brd2+/-
      males have a decreased clonic, and females a decreased tonic-clonic, seizure
      threshold. Additionally, long-term EEG/video recordings captured spontaneous
      seizures in three out of five recorded Brd2+/- female mice. Anatomical analysis
      of specific regions of the brain further revealed significant differences in
      Brd2+/- vs +/+ mice. Specifically, there were decreases in the numbers of
      GABAergic (parvalbumin- or GAD67-immunopositive) neurons along the basal ganglia
      pathway, i.e., in the neocortex and striatum of Brd2+/- mice, compared to Brd2+/+
      mice. There were also fewer GABAergic neurons in the substantia nigra reticulata
      (SNR), yet there was a minor, possibly compensatory increase in the GABA
      producing enzyme GAD67 in these SNR cells. Further, GAD67 expression in the
      superior colliculus and ventral medial thalamic nucleus, the main SNR outputs,
      was significantly decreased in Brd2+/- mice, further supporting GABA
      downregulation. Our data show that the non-channel-encoding, developmentally
      critical Brd2 gene is associated with i) sex-specific increases in seizure
      susceptibility, ii) the development of spontaneous seizures, and iii) seizure
      related anatomical changes in the GABA system, supporting BRD2's involvement in
      human IGE.

PMID- 21887293
TI  - Loss of Niemann-Pick C1 or C2 protein results in similar biochemical changes
      suggesting that these proteins function in a common lysosomal pathway.
AB  - Niemann-Pick Type C (NPC) disease is a lysosomal storage disorder characterized
      by accumulation of unesterified cholesterol and other lipids in the endolysosomal
      system. NPC disease results from a defect in either of two distinct cholesterol
      binding proteins: a transmembrane protein, NPC1, and a small soluble protein,
      NPC2. NPC1 and NPC2 are thought to function closely in the export of lysosomal
      cholesterol with both proteins binding cholesterol in vitro but they may have
      unrelated lysosomal roles. To investigate this possibility, we compared
      biochemical consequences of the loss of either protein. Analyses of lysosome
      enriched subcellular fractions from brain and liver revealed similar decreases in
      buoyant densities of lysosomes from NPC1 or NPC2 deficient mice compared to
      controls. The subcellular distribution of both proteins was similar and
      paralleled a lysosomal marker. In liver, absence of either NPC1 or NPC2 resulted
      in similar alterations in the carbohydrate processing of the lysosomal protease,
      tripeptidyl peptidase I. These results highlight biochemical alterations in the
      lysosomal system of the NPC-mutant mice that appear secondary to lipid storage.
      In addition, the similarity in biochemical phenotypes resulting from either NPC1
      or NPC2 deficiency supports models in which the function of these two proteins
      within lysosomes are linked closely.

PMID- 21887294
TI  - Comprehensive assessment of host responses to ionizing radiation by nuclear
      factor-kappaB bioluminescence imaging-guided transcriptomic analysis.
AB  - The aim of this study was to analyze the host responses to ionizing radiation by
      nuclear factor-kappaB (NF-kappaB) bioluminescence imaging-guided transcriptomic
      tool. Transgenic mice carrying the NF-kappaB-driven luciferase gene were exposed
      to a single dose of 8.5 Gy total-body irradiation. In vivo imaging showed that a
      maximal NF-kappaB-dependent bioluminescent intensity was observed at 3 h after
      irradiation and ex vivo imaging showed that liver, intestine, and brain displayed
      strong NF-kappaB activations. Microarray analysis of these organs showed that
      irradiation altered gene expression signatures in an organ-specific manner and
      several pathways associated with metabolism and immune system were significantly
      altered. Additionally, the upregulation of fatty acid binding protein 4, serum
      amyloid A2, and serum amyloid A3 genes, which participate in both inflammation
      and lipid metabolism, suggested that irradiation might affect the cross pathways
      of metabolism and inflammation. Moreover, the alteration of chemokine (CC-motif)
      ligand 5, chemokine (CC-motif) ligand 20, and Jagged 1 genes, which are involved
      in the inflammation and enterocyte proliferation, suggested that these genes
      might be involved in the radiation enteropathy. In conclusion, this report
      describes the comprehensive evaluation of host responses to ionizing radiation.
      Our findings provide the fundamental information about the in vivo NF-kappaB
      activity and transcriptomic pattern after irradiation. Moreover, novel targets
      involved in radiation injury are also suggested.

PMID- 21887295
TI  - Synaptic reorganization in the adult rat's ventral cochlear nucleus following its
      total sensory deafferentation.
AB  - Ablation of a cochlea causes total sensory deafferentation of the cochlear
      nucleus in the brainstem, providing a model to investigate nervous degeneration
      and formation of new synaptic contacts in the adult brain. In a quantitative
      electron microscopical study on the plasticity of the central auditory system of
      the Wistar rat, we first determined what fraction of the total number of synaptic
      contact zones (SCZs) in the anteroventral cochlear nucleus (AVCN) is attributable
      to primary sensory innervation and how many synapses remain after total
      unilateral cochlear ablation. Second, we attempted to identify the potential for
      a deafferentation-dependent synaptogenesis. SCZs were ultrastructurally
      identified before and after deafferentation in tissue treated for ethanolic
      phosphotungstic acid (EPTA) staining. This was combined with pre-embedding
      immunocytochemistry for gephyrin identifying inhibitory SCZs, the growth
      associated protein GAP-43, glutamate, and choline acetyltransferase. A
      stereological analysis of EPTA stained sections revealed 1.11+/-0.09
      (S.E.M.)*10(9) SCZs per mm(3) of AVCN tissue. Within 7 days of deafferentation,
      this number was down by 46%. Excitatory and inhibitory synapses were
      differentially affected on the side of deafferentation. Excitatory synapses were
      quickly reduced and then began to increase in number again, necessarily being
      complemented from sources other than cochlear neurons, while inhibitory synapses
      were reduced more slowly and continuously. The result was a transient rise of the
      relative fraction of inhibitory synapses with a decline below original levels
      thereafter. Synaptogenesis was inferred by the emergence of morphologically
      immature SCZs that were consistently associated with GAP-43 immunoreactivity.
      SCZs of this type were estimated to make up a fraction of close to 30% of the
      total synaptic population present by ten weeks after sensory deafferentation. In
      conclusion, there appears to be a substantial potential for network
      reorganization and synaptogenesis in the auditory brainstem after loss of
      hearing, even in the adult brain.

PMID- 21887296
TI  - Reverse effect of mammalian hypocalcemic cortisol in fish: cortisol stimulates
      Ca2+ uptake via glucocorticoid receptor-mediated vitamin D3 metabolism.
AB  - Cortisol was reported to downregulate body-fluid Ca(2+) levels in mammals but was
      proposed to show hypercalcemic effects in teleostean fish. Fish, unlike
      terrestrial vertebrates, obtain Ca(2+) from the environment mainly via the gills
      and skin rather than by dietary means, and have to regulate the Ca(2+) uptake
      functions to cope with fluctuating Ca(2+) levels in aquatic environments.
      Cortisol was previously found to regulate Ca(2+) uptake in fish; however, the
      molecular mechanism behind this is largely unclear. Zebrafish were used as a
      model to explore this issue. Acclimation to low-Ca(2+) fresh water stimulated
      Ca(2+) influx and expression of epithelial calcium channel (ecac), 11beta
      hydroxylase and the glucocorticoid receptor (gr). Exogenous cortisol increased
      Ca(2+) influx and the expressions of ecac and hydroxysteroid 11-beta
      dehydrogenase 2 (hsd11b2), but downregulated 11beta-hydroxylase and the gr with
      no effects on other Ca(2+) transporters or the mineralocorticoid receptor (mr).
      Morpholino knockdown of the GR, but not the MR, was found to impair zebrafish
      Ca(2+) uptake function by inhibiting the ecac expression. To further explore the
      regulatory mechanism of cortisol in Ca(2+) uptake, the involvement of vitamin
      D(3) was analyzed. Cortisol stimulated expressions of vitamin D-25hydroxylase
      (cyp27a1), cyp27a1 like (cyp27a1l), 1alpha-OHase (cyp27b1) at 3 dpf through GR,
      the first time to demonstrate the relationship between cortisol and vitamin D(3)
      in fish. In conclusion, cortisol stimulates ecac expression to enhance Ca(2+)
      uptake functions, and this control pathway is suggested to be mediated by the GR.
      Lastly, cortisol also could mediate vitamin D(3) signaling to stimulate Ca(2+)
      uptake in zebrafish.

PMID- 21887297
TI  - Modulation of toxin stability by 4-phenylbutyric acid and negatively charged
      phospholipids.
AB  - AB toxins such as ricin and cholera toxin (CT) consist of an enzymatic A domain
      and a receptor-binding B domain. After endocytosis of the surface-bound toxin,
      both ricin and CT are transported by vesicle carriers to the endoplasmic
      reticulum (ER). The A subunit then dissociates from its holotoxin, unfolds, and
      crosses the ER membrane to reach its cytosolic target. Since protein unfolding at
      physiological temperature and neutral pH allows the dissociated A chain to attain
      a translocation-competent state for export to the cytosol, the underlying
      regulatory mechanisms of toxin unfolding are of paramount biological interest.
      Here we report a biophysical analysis of the effects of anionic phospholipid
      membranes and two chemical chaperones, 4-phenylbutyric acid (PBA) and glycerol,
      on the thermal stabilities and the toxic potencies of ricin toxin A chain (RTA)
      and CT A1 chain (CTA1). Phospholipid vesicles that mimic the ER membrane
      dramatically decreased the thermal stability of RTA but not CTA1. PBA and
      glycerol both inhibited the thermal disordering of RTA, but only glycerol could
      reverse the destabilizing effect of anionic phospholipids. In contrast, PBA was
      able to increase the thermal stability of CTA1 in the presence of anionic
      phospholipids. PBA inhibits cellular intoxication by CT but not ricin, which is
      explained by its ability to stabilize CTA1 and its inability to reverse the
      destabilizing effect of membranes on RTA. Our data highlight the toxin-specific
      intracellular events underlying ER-to-cytosol translocation of the toxin A chain
      and identify a potential means to supplement the long-term stabilization of toxin
      vaccines.

PMID- 21887298
TI  - Combined SAXS/EM based models of the S. elongatus post-translational circadian
      oscillator and its interactions with the output His-kinase SasA.
AB  - The circadian clock in the cyanobacterium Synechococcus elongatus is composed of
      a post-translational oscillator (PTO) that can be reconstituted in vitro from
      three different proteins in the presence of ATP and a transcription-translation
      feedback loop (TTFL). The homo-hexameric KaiC kinase, phosphatase and ATPase
      alternates between hypo- and hyper-phosphorylated states over the 24-h cycle,
      with KaiA enhancing phosphorylation, and KaiB antagonizing KaiA and promoting
      KaiC subunit exchange. SasA is a His kinase that relays output signals from the
      PTO formed by the three Kai proteins to the TTFL. Although the crystal structures
      for all three Kai proteins are known, atomic resolution structures of Kai and
      Kai/SasA protein complexes have remained elusive. Here, we present models of the
      KaiAC and KaiBC complexes derived from solution small angle X-ray scattering
      (SAXS), which are consistent with previous EM based models. We also present a
      combined SAXS/EM model of the KaiC/SasA complex, which has two N-terminal SasA
      sensory domains occupying positions on the C-terminal KaiC ring reminiscent of
      the orientations adopted by KaiB dimers. Using EM we demonstrate that KaiB and
      SasA compete for similar binding sites on KaiC. We also propose an EM based model
      of the ternary KaiABC complex that is consistent with the sequestering of KaiA by
      KaiB on KaiC during the PTO dephosphorylation phase. This work provides the first
      3D-catalogue of protein-protein interactions in the KaiABC PTO and the output
      pathway mediated by SasA.

PMID- 21887299
TI  - Influenza-specific T cells from older people are enriched in the late effector
      subset and their presence inversely correlates with vaccine response.
AB  - T cells specific for persistent pathogens accumulate with age and express markers
      of immune senescence. In contrast, much less is known about the state of T cell
      memory for acutely infecting pathogens. Here we examined T cell responses to
      influenza in human peripheral blood mononuclear cells from older (>64) and
      younger (<40) donors using whole virus restimulation with influenza A (A/PR8/34)
      ex vivo. Although most donors had pre-existing influenza reactive T cells as
      measured by IFNgamma production, older donors had smaller populations of
      influenza-responsive T cells than young controls and had lost a significant
      proportion of their CD45RA-negative functional memory population. Despite this
      apparent dysfunction in a proportion of the older T cells, both old and young
      donors' T cells from 2008 could respond to A/California/07/2009 ex vivo. For HLA
      A2+ donors, MHC tetramer staining showed that a higher proportion of influenza
      specific memory CD8 T cells from the 65+ group co-express the markers killer cell
      lectin-like receptor G1 (KLRG1) and CD57 compared to their younger counterparts.
      These markers have previously been associated with a late differentiation state
      or immune senescence. Thus, memory CD8 T cells to an acutely infecting pathogen
      show signs of advanced differentiation and functional deterioration with age.
      There was a significant negative correlation between the frequency of
      KLRG1(+)CD57(+) influenza M1-specific CD8 T cells pre-vaccination and the ability
      to make antibodies in response to vaccination with seasonal trivalent inactivated
      vaccine, whereas no such trend was observed when the total CD8(+)KLRG1(+)CD57(+)
      population was analyzed. These results suggest that the state of the influenza
      specific memory CD8 T cells may be a predictive indicator of a vaccine responsive
      healthy immune system in old age.

PMID- 21887300
TI  - A weak neutralizing antibody response to hepatitis C virus envelope glycoprotein
      enhances virus infection.
AB  - We have completed a phase 1 safety and immunogenicity trial with hepatitis C
      virus (HCV) envelope glycoproteins, E1 and E2, with MF59 adjuvant as a candidate
      vaccine. Neutralizing activity to HCV genotype 1a was detected in approximately
      25% of the vaccinee sera. In this study, we evaluated vaccinee sera from poor
      responders as a potential source of antibody dependent enhancement (ADE) of HCV
      infection. Sera with poor neutralizing activity enhanced cell culture grown HCV
      genotype 1a or 2a, and surrogate VSV/HCV pseudotype infection titer, in a
      dilution dependent manner. Surrogate pseudotypes generated from individual HCV
      glycoproteins suggested that antibody to the E2 glycoprotein; but not the E1
      glycoprotein, was the principle target for enhancing infection. Antibody specific
      to FcRII expressed on the hepatic cell surface or to the Fc portion of Ig blocked
      enhancement of HCV infection by vaccinee sera. Together, the results from in
      vitro studies suggested that enhancement of viral infectivity may occur in the
      absence of a strong antibody response to HCV envelope glycoproteins.

PMID- 21887301
TI  - Identification of M. tuberculosis-specific Th1 cells expressing CD69 generated in
      vivo in pleural fluid cells from patients with tuberculous pleurisy.
AB  - Th1 cell-mediated immune responses at the site of active infection are important
      to restrict the growth of M. tuberculosis (MTB) and for the spontaneous
      resolution of patients with tuberculous pleurisy (TBP). In the present study, we
      found that without any stimulation, CD4(+) T cells in pleural fluid cells (PFCs)
      from patients with TBP expressed significantly higher levels of CD69 than PBMCs
      from patients with tuberculosis (TB) or healthy donors. CD4(+)CD69(+) T cells
      expressed T-bet and IL-12Rbeta2. After stimulation with MTB-specific antigens,
      CD4(+)CD69(+) T cells expressed significantly higher levels of IFN-gamma, IL-2
      and TNF-alpha than CD4(+)CD69(-) T cells, demonstrating that CD4(+)CD69(+) T
      cells were MTB-specific Th1 cells. In addition, CD4(+)CD69(+) T cells were mostly
      polyfunctional Th1 cells that simultaneously produced IFN-gamma, IL-2, TNF-alpha
      and displayed an effector or effector memory phenotype (CD45RA(-)CCR7(-)CD62L(
      )CD27(-)). Moreover, the percentages of CD4(+)CD69(+) T cells were significantly
      and positively correlated with polyfunctional T cells. Interestingly, sorted
      CD4(+)CD69(+) but not CD4(+)CD69(-) fractions by flow cytometry produced IFN
      gamma, IL-2 and TNF-alpha that were significantly regulated by CD4(+)CD25(+) Treg
      cells. Taken together, based on the expression of CD69, we found a direct
      quantitative and qualitative method to detect and evaluate the in vivo generated
      MTB-specific polyfunctional CD4(+) T cells in PFCs from patients with TBP. This
      method can be used for the potential diagnosis and enrichment or isolation of MTB
      specific Th1 cells in the investigations.

PMID- 21887302
TI  - Inhibition of SARS pseudovirus cell entry by lactoferrin binding to heparan
      sulfate proteoglycans.
AB  - It has been reported that lactoferrin (LF) participates in the host immune
      response against Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)
      invasion by enhancing NK cell activity and stimulating neutrophil aggregation and
      adhesion. We further investigated the role of LF in the entry of SARS pseudovirus
      into HEK293E/ACE2-Myc cells. Our results reveal that LF inhibits SARS pseudovirus
      infection in a dose-dependent manner. Further analysis suggested that LF was able
      to block the binding of spike protein to host cells at 4 degrees C, indicating
      that LF exerted its inhibitory function at the viral attachment stage. However,
      LF did not disrupt the interaction of spike protein with angiotensin-converting
      enzyme 2 (ACE2), the functional receptor of SARS-CoV. Previous studies have shown
      that LF colocalizes with the widely distributed cell-surface heparan sulfate
      proteoglycans (HSPGs). Our experiments have also confirmed this conclusion.
      Treatment of the cells with heparinase or exogenous heparin prevented binding of
      spike protein to host cells and inhibited SARS pseudovirus infection,
      demonstrating that HSPGs provide the binding sites for SARS-CoV invasion at the
      early attachment phase. Taken together, our results suggest that, in addition to
      ACE2, HSPGs are essential cell-surface molecules involved in SARS-CoV cell entry.
      LF may play a protective role in host defense against SARS-CoV infection through
      binding to HSPGs and blocking the preliminary interaction between SARS-CoV and
      host cells. Our findings may provide further understanding of SARS-CoV
      pathogenesis and aid in treatment of this deadly disease.

PMID- 21887303
TI  - Impact of educational intervention concerning awareness and behaviors relating to
      avian influenza (H5N1) in a high-risk population in Vietnam.
AB  - BACKGROUND: Early initiation of treatment is essential for treatment of avian
      influenza A/H5N1 viral infection in humans, as the disease can lead to rapid
      development of severe pneumonia which can result in death. Contact with infected
      poultry is known to be a significant risk factor for contraction of H5N1
      infection. However, handling and encountering poultry are a part of most peoples'
      daily lives, especially in rural communities in Vietnam where epidemic outbreaks
      among poultry have been continuously reported. Enhancing proper knowledge
      relating to H5N1 and to the importance of early initiation of treatment are
      crucial. The aim of this study was to develop an effective educational program to
      enhance awareness of H5N1 and motivate people to access to health care earlier
      when H5N1 infection is suspected or likely. METHODOLOGY AND PRINCIPAL FINDINGS: A
      study was conducted in two agricultural communities (intervention and control
      groups) in the Ninh Binh province in Vietnam, where epidemic outbreaks of avian
      influenza have recently occurred in birds. A unique educational intervention was
      developed and provided to the intervention group, and no intervention was
      provided to the control group. A knowledge, attitude and practice (KAP) survey
      was conducted in both groups with a face-to-face interview by trained local
      healthcare workers at time points before and after the educational intervention.
      KAP scores were compared between the different time points and between the
      groups. How educational intervention influenced awareness relating to H5N1 and
      accessibility of healthcare in the population was analyzed. The study indicated
      an increased awareness of H5N1 and increased reliance on local health care
      workers. CONCLUSIONS: The novel educational program which was developed for this
      study impacted awareness of H5N1, and resulted in more people seeking early
      access to healthcare, and also resulted in earlier medical intervention for
      patients with H5N1 avian influenza infection in Vietnam.

PMID- 21887304
TI  - Efficient detection of proteins retro-translocated from the ER to the cytosol by
      in vivo biotinylation.
AB  - Retro-translocation from the ER to the cytosol of proteins within the secretory
      pathway takes place on misfolded molecules that are targeted for degradation by
      the cytosolically located 26S proteasome complex. Retro-translocation occurs also
      for other proteins (such as calreticulin) that, despite being synthesized and
      transported to the ER, are in part dislocated to the cytosol. We have taken
      advantage of the E. coli derived biotin-ligase (BirA) expressed in the cytosol of
      mammalian cells to specifically biotin-label in vivo proteins within the
      secretory pathway that undergo retro-translocation. We validated the method using
      four different proteins that are known to undergo retro-translocation upon
      different conditions: the human trans-membrane protein MHC class-I alpha chain
      (MHC-Ialpha), the Null Hong Kong mutant of the secretory alpha1 anti-trypsin (NHK
      alpha1AT), the immunoglobulin heavy chain (HC) and the ER chaperone calreticulin
      (Crt). We observed specific mono-biotinylation of cytosolically dislocated
      molecules, resulting in a novel, reliable way of determining the extent of retro
      translocation.

PMID- 21887305
TI  - Icaritin shows potent anti-leukemia activity on chronic myeloid leukemia in vitro
      and in vivo by regulating MAPK/ERK/JNK and JAK2/STAT3 /AKT signalings.
AB  - PURPOSE: To explore the effects of Icaritin on chronic myeloid leukemia (CML)
      cells and underlying mechanisms. METHOD: CML cells were incubated with various
      concentration of Icaritin for 48 hours, the cell proliferation was analyzed by
      MTT and the apoptosis was assessed with Annexin V and Hoechst 33258 staining.
      Cell hemoglobinization was determined. Western blotting was used to evaluate the
      expressions of MAPK/ERK/JNK signal pathway and Jak-2/Phorpho-Stat3/Phorsph-Akt
      network-related protein. NOD-SCID nude mice were applied to demonstrate the anti
      leukemia effect of Icaritin in vivo. RESULTS: Icaritin potently inhibited
      proliferation of K562 cells (IC50 was 8 uM) and primary CML cells (IC50 was 13.4
      uM for CML-CP and 18 uM for CML-BC), induced CML cells apoptosis and promoted the
      erythroid differentiation of K562 cells with time-dependent manner. Furthermore,
      Icaritin was able to suppress the growth of primary CD34+ leukemia cells (CML)
      and Imatinib-resistant cells, and to induce apoptosis. In mouse leukemia model,
      Icaritin could prolong lifespan of NOD-SCID nude mice inoculated with K562 cells
      as effective as Imatinib without suppression of bone marrow. Icaritin could up
      regulate phospho-JNK or phospho-C-Jun and down-regulate phospho-ERK, phospho-P
      38, Jak-2, phospho-Stat3 and phospho-Akt expression with dose- or time-dependent
      manner. Icaritin had no influence both on c-Abl and phospho-c-Abl protein
      expression and mRNA levels of Bcr/Abl. CONCLUSION: Icaritin from Chinese herb
      medicine may be a potential anti-CML agent with low adverse effect. The mechanism
      of anti-leukemia for Icaritin is involved in the regulation of Bcr/Abl downstream
      signaling. Icaritin may be useful for an alternative therapeutic choice of
      Imatinib-resistant forms of CML.

PMID- 21887306
TI  - The potential impact of labor choices on the efficacy of marine conservation
      strategies.
AB  - Conservation of marine resources is critical to the wellbeing of human
      communities. Coastal artisanal fishing communities are particularly reliant on
      marine resources for food and for their livelihoods. Management actions aimed at
      marine conservation may lead to unanticipated changes in human behavior that
      influence the ability of conservation programs to achieve their goals. We examine
      how marine conservation strategies may impact labor decisions that influence both
      the ecosystem and human livelihoods using simulation modeling. We consider two
      conservation strategies in the model: direct action through fisheries regulation
      enforcement, and indirect action through land conservation. Our results indicate
      that both strategies can increase the abundance of fish, and thus contribute to
      the maintenance of marine resources. However, our results also show that marine
      fisheries enforcement may negatively impact the livelihoods of human communities.
      Land conservation, on the other hand, potentially enhances the livelihood of the
      human populations. Thus, depending on management objectives, indirect or a
      combination of direct and indirect conservation strategies may be effective at
      achieving conservation and sustainability goals. These results highlight the
      importance of accounting for changes in human behavior resulting from management
      actions in conservation and management.

PMID- 21887307
TI  - Discrete emotion effects on lexical decision response times.
AB  - Our knowledge about affective processes, especially concerning effects on
      cognitive demands like word processing, is increasing steadily. Several studies
      consistently document valence and arousal effects, and although there is some
      debate on possible interactions and different notions of valence, broad agreement
      on a two dimensional model of affective space has been achieved. Alternative
      models like the discrete emotion theory have received little interest in word
      recognition research so far. Using backward elimination and multiple regression
      analyses, we show that five discrete emotions (i.e., happiness, disgust, fear,
      anger and sadness) explain as much variance as two published dimensional models
      assuming continuous or categorical valence, with the variables happiness, disgust
      and fear significantly contributing to this account. Moreover, these effects even
      persist in an experiment with discrete emotion conditions when the stimuli are
      controlled for emotional valence and arousal levels. We interpret this result as
      evidence for discrete emotion effects in visual word recognition that cannot be
      explained by the two dimensional affective space account.

PMID- 21887308
TI  - Low dynamics, high longevity and persistence of sessile structural species
      dwelling on Mediterranean coralligenous outcrops.
AB  - There is still limited understanding of the processes underlying benthic species
      dynamics in marine coastal habitats, which are of disproportionate importance in
      terms of productivity and biodiversity. The life-history traits of long-lived
      benthic species in these habitats are particularly poorly documented. In this
      study, we assessed decadal patterns of population dynamics for ten sponge and
      anthozoan species that play key structural roles in coralligenous outcrops (~25 m
      depth) in two areas of the NW Mediterranean Sea. This study was based on
      examination of a unique long-term photographic series, which allowed analysis of
      population dynamics over extensive spatial and time spans for the very first
      time. Specifically, 671 individuals were censused annually over periods of 25-,
      15-, and 5-years. This long-term study quantitatively revealed a common life
      history pattern among the ten studied species, despite the fact they present
      different growth forms. Low mortality rates (3.4% yr(-1) for all species
      combined) and infrequent recruitment events (mean value of 3.1+/-0.5 SE recruits
      yr(-1)) provided only a very small fraction of the new colonies required to
      maintain population sizes. Overall, annual mortality and recruitment rates did
      not differ significantly among years; however, some species displayed important
      mortality events and recruitment pulses, indicating variability among species.
      Based on the growth rates of these 10 species, we projected their longevity and,
      obtained a mean estimated age of 25-200 years. Finally, the low to moderate
      turnover rates (mean value 0.80% yr(-1)) observed among the coralligenous species
      were in agreement with their low dynamics and persistence. These results offer
      solid baseline data and reveal that these habitats are among the most vulnerable
      to the current increases of anthropogenic disturbances.

PMID- 21887309
TI  - Farnesoid X receptor (FXR) activation and FXR genetic variation in inflammatory
      bowel disease.
AB  - BACKGROUND: We previously showed that activation of the bile salt nuclear
      receptor Farnesoid X Receptor (FXR) protects against intestinal inflammation in
      mice. Reciprocally, these inflammatory mediators may decrease FXR activation. We
      investigated whether FXR activation is repressed in the ileum and colon of
      inflammatory bowel disease (IBD) patients in remission. Additionally, we
      evaluated whether genetic variation in FXR is associated with IBD. METHODS: mRNA
      expression of FXR and FXR target gene SHP was determined in ileal and colonic
      biopsies of patients with Crohn's colitis (n = 15) and ulcerative colitis (UC; n
      = 12), all in clinical remission, and healthy controls (n = 17). Seven common
      tagging SNPs and two functional SNPs in FXR were genotyped in 2355 Dutch IBD
      patients (1162 Crohn's disease (CD) and 1193 UC) and in 853 healthy controls.
      RESULTS: mRNA expression of SHP in the ileum is reduced in patients with Crohn's
      colitis but not in patients with UC compared to controls. mRNA expression of
      villus marker Villin was correlated with FXR and SHP in healthy controls, a
      correlation that was weaker in UC patients and absent in CD patients. None of the
      SNPs was associated with IBD, UC or CD, nor with clinical subgroups of CD.
      CONCLUSIONS: FXR activation in the ileum is decreased in patients with Crohn's
      colitis. This may be secondary to altered enterohepatic circulation of bile salts
      or transrepression by inflammatory signals but does not seem to be caused by the
      studied SNPs in FXR. Increasing FXR activity by synthetic FXR agonists may have
      benefit in CD patients.

PMID- 21887310
TI  - Nuclear factor-kappaB-dependent epithelial to mesenchymal transition induced by
      HIF-1alpha activation in pancreatic cancer cells under hypoxic conditions.
AB  - BACKGROUND: Epithelial to mesenchymal transition (EMT) induced by hypoxia is one
      of the critical causes of treatment failure in different types of human cancers.
      NF-kappaB is closely involved in the progression of EMT. Compared with HIF
      1alpha, the correlation between NF-kappaB and EMT during hypoxia has been less
      studied, and although the phenomenon was observed in the past, the molecular
      mechanisms involved remained unclear. METHODOLOGY/PRINCIPAL FINDINGS: Here, we
      report that hypoxia or overexpression of hypoxia-inducible factor-1alpha (HIF
      1alpha) promotes EMT in pancreatic cancer cells. On molecular or pharmacologic
      inhibition of NF-kappaB, hypoxic cells regained expression of E-cadherin, lost
      expression of N-cadherin, and attenuated their highly invasive and drug-resistant
      phenotype. Introducing a pcDNA3.0/HIF-1alpha into pancreatic cancer cells under
      normoxic conditions heightened NF-kappaB activity, phenocopying EMT effects
      produced by hypoxia. Conversely, inhibiting the heightened NF-kappaB activity in
      this setting attenuated the EMT phenotype. CONCLUSIONS/SIGNIFICANCE: These
      results suggest that hypoxia or overexpression of HIF-1alpha induces the EMT that
      is largely dependent on NF-kappaB in pancreatic cancer cells.

PMID- 21887311
TI  - A herbivorous mite down-regulates plant defence and produces web to exclude
      competitors.
AB  - Herbivores may interact with each other through resource competition, but also
      through their impact on plant defence. We recently found that the spider mite
      Tetranychus evansi down-regulates plant defences in tomato plants, resulting in
      higher rates of oviposition and population growth on previously attacked than on
      unattacked leaves. The danger of such down-regulation is that attacked plants
      could become a more profitable resource for heterospecific competitors, such as
      the two-spotted spider mite Tetranychus urticae. Indeed, T. urticae had an almost
      2-fold higher rate of oviposition on leaf discs on which T. evansi had fed
      previously. In contrast, induction of direct plant defences by T. urticae
      resulted in decreased oviposition by T. evansi. Hence, both herbivores affect
      each other through induced plant responses. However, when populations of T.
      evansi and T. urticae competed on the same plants, populations of the latter
      invariably went extinct, whereas T. evansi was not significantly affected by the
      presence of its competitor. This suggests that T. evansi can somehow prevent its
      competitor from benefiting from the down-regulated plant defence, perhaps by
      covering it with a profuse web. Indeed, we found that T. urticae had difficulties
      reaching the leaf surface to feed when the leaf was covered with web produced by
      T. evansi. Furthermore, T. evansi produced more web when exposed to damage or
      other cues associated with T. urticae. We suggest that the silken web produced by
      T. evansi serves to prevent competitors from profiting from down-regulated plant
      defences.

PMID- 21887312
TI  - The neuronal PAS domain protein 4 (Npas4) is required for new and reactivated
      fear memories.
AB  - The Neuronal PAS domain protein 4 (Npas4) is a neuronal activity-dependent
      immediate early gene that has recently been identified as a transcription factor
      which regulates the transcription of genes that control inhibitory synapse
      development and synaptic plasticity. The role Npas4 in learning and memory,
      however, is currently unknown. Here, we systematically examine the role of Npas4
      in auditory Pavlovian fear conditioning, an amygdala-dependent form of emotional
      learning. In our first series of experiments, we show that Npas4 mRNA and protein
      are regulated in the rat lateral nucleus of the amygdala (LA) in a learning
      dependent manner. Further, knockdown of Npas4 protein in the LA via adeno
      associated viral (AAV) mediated gene delivery of RNAi was observed to impair fear
      memory formation, while innate fear and the expression of fear memory were not
      affected. In our second series of experiments, we show that Npas4 protein is
      regulated in the LA by retrieval of an auditory fear memory and that knockdown of
      Npas4 in the LA impairs retention of a reactivated, but not a non-reactivated,
      fear memory. Collectively, our findings provide the first comprehensive look at
      the functional role of Npas4 in learning and memory.

PMID- 21887313
TI  - Ischemic tolerance protects the rat retina from glaucomatous damage.
AB  - Glaucoma is a leading cause of acquired blindness which may involve an ischemic
      like insult to retinal ganglion cells and optic nerve head. We investigated the
      effect of a weekly application of brief ischemia pulses (ischemic conditioning)
      on the rat retinal damage induced by experimental glaucoma. Glaucoma was induced
      by weekly injections of chondroitin sulfate (CS) in the rat eye anterior chamber.
      Retinal ischemia was induced by increasing intraocular pressure to 120 mmHg for 5
      min; this maneuver started after 6 weekly injections of vehicle or CS and was
      weekly repeated in one eye, while the contralateral eye was submitted to a sham
      procedure. Glaucoma was evaluated in terms of: i) intraocular pressure (IOP), ii)
      retinal function (electroretinogram (ERG)), iii) visual pathway function (visual
      evoked potentials, (VEPs)) iv) histology of the retina and optic nerve head.
      Retinal thiobarbituric acid substances levels were assessed as an index of lipid
      peroxidation. Ischemic conditioning significantly preserved ERG, VEPs, as well as
      retinal and optic nerve head structure from glaucomatous damage, without changes
      in IOP. Moreover, ischemia pulses abrogated the increase in lipid peroxidation
      induced by experimental glaucoma. These results indicate that induction of
      ischemic tolerance could constitute a fertile avenue for the development of new
      therapeutic strategies in glaucoma treatment.

PMID- 21887314
TI  - Specificity and actions of an arylaspartate inhibitor of glutamate transport at
      the Schaffer collateral-CA1 pyramidal cell synapse.
AB  - In this study we characterized the pharmacological selectivity and physiological
      actions of a new arylaspartate glutamate transporter blocker, L-threo-beta
      benzylaspartate (L-TBA). At concentrations up to 100 uM, L-TBA did not act as an
      AMPA receptor (AMPAR) or NMDA receptor (NMDAR) agonist or antagonist when applied
      to outside-out patches from mouse hippocampal CA1 pyramidal neurons. L-TBA had no
      effect on the amplitude of field excitatory postsynaptic potentials (fEPSPs)
      recorded at the Schaffer collateral-CA1 pyramidal cell synapse. Excitatory
      postsynaptic currents (EPSCs) in CA1 pyramidal neurons were unaffected by L-TBA
      in the presence of physiological extracellular Mg(2+) concentrations, but in
      Mg(2+)-free solution, EPSCs were significantly prolonged as a consequence of
      increased NMDAR activity. Although L-TBA exhibited approximately four-fold
      selectivity for neuronal EAAT3 over glial EAAT1/EAAT2 transporter subtypes
      expressed in Xenopus oocytes, the L-TBA concentration-dependence of the EPSC
      charge transfer increase in the absence of Mg(2+) was the same in hippocampal
      slices from EAAT3 +/+ and EAAT3 -/- mice, suggesting that TBA effects were
      primarily due to block of glial transporters. Consistent with this, L-TBA blocked
      synaptically evoked transporter currents in CA1 astrocytes with a potency in
      accord with its block of heterologously expressed glial transporters.
      Extracellular recording in the presence of physiological Mg(2+) revealed that L
      TBA prolonged fEPSPs in a frequency-dependent manner by selectively increasing
      the NMDAR-mediated component of the fEPSP during short bursts of activity. The
      data indicate that glial glutamate transporters play a dominant role in limiting
      extrasynaptic transmitter diffusion and binding to NMDARs. Furthermore, NMDAR
      signaling is primarily limited by voltage-dependent Mg(2+) block during low
      frequency activity, while the relative contribution of transport increases during
      short bursts of higher frequency signaling.

PMID- 21887315
TI  - Neanderthal use of fish, mammals, birds, starchy plants and wood 125-250,000
      years ago.
AB  - Neanderthals are most often portrayed as big game hunters who derived the vast
      majority of their diet from large terrestrial herbivores while birds, fish and
      plants are seen as relatively unimportant or beyond the capabilities of
      Neanderthals. Although evidence for exploitation of other resources (small
      mammals, birds, fish, shellfish, and plants) has been found at certain
      Neanderthal sites, these are typically dismissed as unusual exceptions. The
      general view suggests that Neanderthal diet may broaden with time, but that this
      only occurs sometime after 50,000 years ago. We present evidence, in the form of
      lithic residue and use-wear analyses, for an example of a broad-based subsistence
      for Neanderthals at the site of Payre, Ardeche, France (beginning of MIS 5/end of
      MIS 6 to beginning of MIS 7/end of MIS 8; approximately 125-250,000 years ago).
      In addition to large terrestrial herbivores, Neanderthals at Payre also exploited
      starchy plants, birds, and fish. These results demonstrate a varied subsistence
      already in place with early Neanderthals and suggest that our ideas of
      Neanderthal subsistence are biased by our dependence on the zooarchaeological
      record and a deep-seated intellectual emphasis on big game hunting.

PMID- 21887316
TI  - Immunoproteasome-deficiency has no effects on NK cell education, but confers
      lymphocytes into targets for NK cells in infected wild-type mice.
AB  - Natural killer (NK) cells are part of the innate immune system and contribute to
      the eradication of virus infected cells and tumors. NK cells express inhibitory
      and activating receptors and their decision to kill a target cell is based on the
      balance of signals received through these receptors. MHC class I molecules are
      recognized by inhibitory receptors, and their presence during NK cell education
      influences the responsiveness of peripheral NK cells. We here demonstrate that
      mice with reduced MHC class I cell surface expression, due to deficiency of
      immunoproteasomes, have responsive NK cells in the periphery, indicating that the
      lower MHC class I levels do not alter NK cell education. Following adoptive
      transfer into wild-type (wt) recipients, immunoproteasome-deficient splenocytes
      are tolerated in naive but rejected in virus-infected recipients, in an NK cell
      dependent fashion. These results indicate that the relatively low MHC class I
      levels are sufficient to protect these cells from rejection by wt NK cells, but
      that this tolerance is broken in infection, inducing an NK cell-dependent
      rejection of immunoproteasome-deficient cells.

PMID- 21887317
TI  - Evidence for an auditory fovea in the New Zealand kiwi (Apteryx mantelli).
AB  - Kiwi are rare and strictly protected birds of iconic status in New Zealand. Yet,
      perhaps due to their unusual, nocturnal lifestyle, surprisingly little is known
      about their behaviour or physiology. In the present study, we exploited known
      correlations between morphology and physiology in the avian inner ear and
      brainstem to predict the frequency range of best hearing in the North Island
      brown kiwi. The mechanosensitive hair bundles of the sensory hair cells in the
      basilar papilla showed the typical change from tall bundles with few stereovilli
      to short bundles with many stereovilli along the apical-to-basal tonotopic axis.
      In contrast to most birds, however, the change was considerably less in the basal
      half of the epithelium. Dendritic lengths in the brainstem nucleus laminaris also
      showed the typical change along the tonotopic axis. However, as in the basilar
      papilla, the change was much less pronounced in the presumed high-frequency
      regions. Together, these morphological data suggest a fovea-like
      overrepresentation of a narrow high-frequency band in kiwi. Based on known
      correlations of hair-cell microanatomy and physiological responses in other
      birds, a specific prediction for the frequency representation along the basilar
      papilla of the kiwi was derived. The predicted overrepresentation of
      approximately 4-6 kHz matches potentially salient frequency bands of kiwi
      vocalisations and may thus be an adaptation to a nocturnal lifestyle in which
      auditory communication plays a dominant role.

PMID- 21887318
TI  - Evolutionary pathways of the pandemic influenza A (H1N1) 2009 in the UK.
AB  - The emergence of the influenza (H1N1) 2009 virus provided a unique opportunity to
      study the evolution of a pandemic virus following its introduction into the human
      population. Virological and clinical surveillance in the UK were comprehensive
      during the first and second waves of the pandemic in 2009, with extensive
      laboratory confirmation of infection allowing a detailed sampling of
      representative circulating viruses. We sequenced the complete coding region of
      the haemagglutinin (HA) segment of 685 H1N1 pandemic viruses selected without
      bias during two waves of pandemic in the UK (April-December 2009). Phylogenetic
      analysis showed that although temporal accumulation of amino acid changes was
      observed in the HA sequences, the overall diversity was less than that typically
      seen for seasonal influenza A H1N1 or H3N2. There was co-circulation of multiple
      variants as characterised by signature amino acid changes in the HA. A specific
      substitution (S203T) became predominant both in UK and global isolates. No
      antigenic drift occurred during 2009 as viruses with greater than four-fold
      reduction in their haemagglutination inhibition (HI) titre ("low reactors") were
      detected in a low proportion (3%) and occurred sporadically. Although some
      limited antigenic divergence in viruses with four-fold reduction in HI titre
      might be related to the presence of 203T, additional studies are needed to test
      this hypothesis.

PMID- 21887319
TI  - Identifying Schistosoma japonicum excretory/secretory proteins and their
      interactions with host immune system.
AB  - Schistosoma japonicum is a major infectious agent of schistosomiasis. It has been
      reported that large number of proteins excreted and secreted by S. japonicum
      during its life cycle are important for its infection and survival in definitive
      hosts. These proteins can be used as ideal candidates for vaccines or drug
      targets. In this work, we analyzed the protein sequences of S. japonicum and
      found that compared with other proteins in S. japonicum, excretory/secretory (ES)
      proteins are generally longer, more likely to be stable and enzyme, more likely
      to contain immune-related binding peptides and more likely to be involved in
      regulation and metabolism processes. Based on the sequence difference between ES
      and non-ES proteins, we trained a support vector machine (SVM) with much higher
      accuracy than existing approaches. Using this SVM, we identified 191 new ES
      proteins in S. japonicum, and further predicted 7 potential interactions between
      these ES proteins and human immune proteins. Our results are useful to understand
      the pathogenesis of schistosomiasis and can serve as a new resource for vaccine
      or drug targets discovery for anti-schistosome.

PMID- 21887320
TI  - Sex ratio at birth and mortality rates are negatively related in humans.
AB  - Evolutionary theory posits that resource availability and parental investment
      ability could signal offspring sex selection, in order to maximize reproductive
      returns. Non-human studies have provided evidence for this phenomenon, and
      maternal condition around the time of conception has been identified as most
      important factor that influence offspring sex selection. However, studies on
      humans have reported inconsistent results, mostly due to use of disparate
      measures as indicators of maternal condition. In the present study, the cross
      cultural differences in human natal sex ratio were analyzed with respect to
      indirect measures of condition namely, life expectancy and mortality rate.
      Multiple regression modeling suggested that mortality rates have distinct
      predictive power independent of cross-cultural differences in fertility, wealth
      and latitude that were earlier shown to predict sex ratio at birth. These
      findings suggest that sex ratio variation in humans may relate to differences in
      parental and environmental conditions.

PMID- 21887321
TI  - Collective dynamics of active cytoskeletal networks.
AB  - Self organization mechanisms are essential for the cytoskeleton to adapt to the
      requirements of living cells. They rely on the intricate interplay of
      cytoskeletal filaments, crosslinking proteins and molecular motors. Here we
      present an in vitro minimal model system consisting of actin filaments, fascin
      and myosin-II filaments exhibiting pulsatile collective dynamics and
      superdiffusive transport properties. Both phenomena rely on the complex
      competition of crosslinking molecules and motor filaments in the network. They
      are only observed if the relative strength of the binding of myosin-II filaments
      to the actin network allows exerting high enough forces to unbind actin/fascin
      crosslinks. This is shown by varying the binding strength of the acto-myosin bond
      and by combining the experiments with phenomenological simulations based on
      simple interaction rules.

PMID- 21887322
TI  - YwdL in Bacillus cereus: its role in germination and exosporium structure.
AB  - In members of the Bacillus cereus group the outermost layer of the spore is the
      exosporium, which interacts with hosts and the environment. Efforts have been
      made to identify proteins of the exosporium but only a few have so far been
      characterised and their role in determining spore architecture and spore function
      is still poorly understood. We have characterised the exosporium protein, YwdL.
      DeltaywdL spores have a more fragile exosporium, subject to damage on repeated
      freeze-thawing, although there is no evidence of altered resistance properties,
      and coats appear intact. Immunogold labelling and Western blotting with anti-YwdL
      antibodies identified YwdL to be located exclusively on the inner surface of the
      exosporium of B. cereus and B. thuringiensis. We conclude that YwdL is important
      for formation of a robust exosporium but is not required to maintain the
      crystalline assembly within the basal layer or for attachment of the hairy nap
      structure. DeltaywdL spores are unable to germinate in response to CaDPA, and
      have altered germination properties, a phenotype that confirms the expected
      defect in localization of the cortex lytic enzyme CwlJ in the coat.

PMID- 21887323
TI  - Divalent metal ion differentially regulates the sequential nicking reactions of
      the GIY-YIG homing endonuclease I-BmoI.
AB  - Homing endonucleases are site-specific DNA endonucleases that function as mobile
      genetic elements by introducing double-strand breaks or nicks at defined
      locations. Of the major families of homing endonucleases, the modular GIY-YIG
      endonucleases are least understood in terms of mechanism. The GIY-YIG homing
      endonuclease I-BmoI generates a double-strand break by sequential nicking
      reactions during which the single active site of the GIY-YIG nuclease domain must
      undergo a substantial reorganization. Here, we show that divalent metal ion plays
      a significant role in regulating the two independent nicking reactions by I-BmoI.
      Rate constant determination for each nicking reaction revealed that limiting
      divalent metal ion has a greater impact on the second strand than the first
      strand nicking reaction. We also show that substrate mutations within the I-BmoI
      cleavage site can modulate the first strand nicking reaction over a 314-fold
      range. Additionally, in-gel DNA footprinting with mutant substrates and modeling
      of an I-BmoI-substrate complex suggest that amino acid contacts to a critical GC
      2 base pair are required to induce a bottom-strand distortion that likely directs
      conformational changes for reaction progress. Collectively, our data implies
      mechanistic roles for divalent metal ion and substrate bases, suggesting that
      divalent metal ion facilitates the re-positioning of the GIY-YIG nuclease domain
      between sequential nicking reactions.

PMID- 21887324
TI  - A comprehensive model of audiovisual perception: both percept and temporal
      dynamics.
AB  - The sparse information captured by the sensory systems is used by the brain to
      apprehend the environment, for example, to spatially locate the source of
      audiovisual stimuli. This is an ill-posed inverse problem whose inherent
      uncertainty can be solved by jointly processing the information, as well as
      introducing constraints during this process, on the way this multisensory
      information is handled. This process and its result--the percept--depend on the
      contextual conditions perception takes place in. To date, perception has been
      investigated and modeled on the basis of either one of two of its dimensions: the
      percept or the temporal dynamics of the process. Here, we extend our previously
      proposed audiovisual perception model to predict both these dimensions to capture
      the phenomenon as a whole. Starting from a behavioral analysis, we use a data
      driven approach to elicit a bayesian network which infers the different percepts
      and dynamics of the process. Context-specific independence analyses enable us to
      use the model's structure to directly explore how different contexts affect the
      way subjects handle the same available information. Hence, we establish that,
      while the percepts yielded by a unisensory stimulus or by the non-fusion of
      multisensory stimuli may be similar, they result from different processes, as
      shown by their differing temporal dynamics. Moreover, our model predicts the
      impact of bottom-up (stimulus driven) factors as well as of top-down factors
      (induced by instruction manipulation) on both the perception process and the
      percept itself.

PMID- 21887325
TI  - Towards online multiresolution community detection in large-scale networks.
AB  - The investigation of community structure in networks has aroused great interest
      in multiple disciplines. One of the challenges is to find local communities from
      a starting vertex in a network without global information about the entire
      network. Many existing methods tend to be accurate depending on a priori
      assumptions of network properties and predefined parameters. In this paper, we
      introduce a new quality function of local community and present a fast local
      expansion algorithm for uncovering communities in large-scale networks. The
      proposed algorithm can detect multiresolution community from a source vertex or
      communities covering the whole network. Experimental results show that the
      proposed algorithm is efficient and well-behaved in both real-world and synthetic
      networks.

PMID- 21887326
TI  - The impact of illicit drug use on spontaneous hepatitis C clearance: experience
      from a large cohort population study.
AB  - BACKGROUND AND AIMS: Acute hepatitis C infection usually ends in chronic
      infection, while in a minority of patients it is spontaneously cleared. The
      current population-based study is performed on a large cohort in Golestan
      province of Iran to examine the demographic correlates of Spontaneous Hepatitis C
      Clearance. METHODS: Serum samples used in this study had been stored in
      biorepository of Golestan Cohort Study. These samples were evaluated for anti
      hepatitis C Virus by third generation Enzyme-linked immunosorbent assay (ELISA).
      Subjects who tested positive were then invited and tested by Recombinant
      Immunoblot Assay (RIBA) and Ribonucleic Acid Polymerase Chain Reaction test
      (PCR). If tested positive for RIBA, subjects were recalled and the two tests were
      re-done after 6 months. Those subjects who again tested positive for RIBA but
      negative for PCR were marked as cases of spontaneous clearance. RESULTS: 49,338
      serum samples were evaluated. The prevalence of Chronic Hepatitis C Virus (CHCV)
      infection based on PCR results was 0.31%. Among those who had acquired hepatitis
      C, the rate of SC was 38%. In multivariate analysis, illicit drug use both
      Injecting Use (OR = 3.271, 95% CI: 1.784-6.000, p-value<0.001) and Non-Injecting
      Use (OR = 1.901, 95% CI: 1.068-3.386, p-value = 0.029) were significant
      correlates of CHCV infection versus SC. CONCLUSIONS: Illicit drug use whether
      intravenous or non-intravenous is the only significant correlate of CHCV, for
      which several underlying mechanisms can be postulated including repeated contacts
      with hepatitis C antigen.

PMID- 21887327
TI  - The Na+/H+ exchanger controls deoxycholic acid-induced apoptosis by a H+
      activated, Na+-dependent ionic shift in esophageal cells.
AB  - Apoptosis resistance is a hallmark of cancer cells. Typically, bile acids induce
      apoptosis. However during gastrointestinal (GI) tumorigenesis the cancer cells
      develop resistance to bile acid-induced cell death. To understand how bile acids
      induce apoptosis resistance we first need to identify the molecular pathways that
      initiate apoptosis in response to bile acid exposure. In this study we examined
      the mechanism of deoxycholic acid (DCA)-induced apoptosis, specifically the role
      of Na(+)/H(+) exchanger (NHE) and Na(+) influx in esophageal cells. In vitro
      studies revealed that the exposure of esophageal cells (JH-EsoAd1, CP-A) to DCA
      (0.2 mM-0.5 mM) caused lysosomal membrane perturbation and transient cytoplasmic
      acidification. Fluorescence microscopy in conjunction with atomic absorption
      spectrophotometry demonstrated that this effect on lysosomes correlated with
      influx of Na(+), subsequent loss of intracellular K(+), an increase of Ca(2+) and
      apoptosis. However, ethylisopropyl-amiloride (EIPA), a selective inhibitor of
      NHE, prevented Na(+), K(+) and Ca(2+) changes and caspase 3/7 activation induced
      by DCA. Ouabain and amphotericin B, two drugs that increase intracellular Na(+)
      levels, induced similar changes as DCA (ion imbalance, caspase3/7 activation). On
      the contrary, DCA-induced cell death was inhibited by medium with low a Na(+)
      concentrations. In the same experiments, we exposed rat ileum ex-vivo to DCA with
      or without EIPA. Severe tissue damage and caspase-3 activation was observed after
      DCA treatment, but EIPA almost fully prevented this response. In summary, NHE
      mediated Na(+) influx is a critical step leading to DCA-induced apoptosis. Cells
      tolerate acidification but evade DCA-induced apoptosis if NHE is inhibited. Our
      data suggests that suppression of NHE by endogenous or exogenous inhibitors may
      lead to apoptosis resistance during GI tumorigenesis.

PMID- 21887328
TI  - Regulation of miR-146a by RelA/NFkB and p53 in STHdh(Q111)/Hdh(Q111) cells, a
      cell model of Huntington's disease.
AB  - Huntington's disease (HD) is caused by the expansion of N-terminal polymorphic
      poly Q stretch of the protein huntingtin (HTT). Deregulated microRNAs and loss of
      function of transcription factors recruited to mutant HTT aggregates could cause
      characteristic transcriptional deregulation associated with HD. We observed
      earlier that expressions of miR-125b, miR-146a and miR-150 are decreased in
      STHdh(Q111)/Hdh(Q111) cells, a model for HD in comparison to those of wild type
      STHdh(Q7)/Hdh(Q7) cells. In the present manuscript, we show by luciferase
      reporter assays and real time PCR that decreased miR-146a expression in
      STHdh(Q111)/Hdh(Q111) cells is due to decreased expression and activity of p65
      subunit of NFkB (RelA/NFkB). By reporter luciferase assay, RT-PCR and western
      blot analysis, we also show that both miR-150 and miR-125b target p53. This
      partially explains the up regulation of p53 observed in HD. Elevated p53
      interacts with RelA/NFkB, reduces its expression and activity and decreases the
      expression of miR-146a, while knocking down p53 increases RelA/NFkB and miR-146a
      expressions. We also demonstrate that expression of p53 is increased and levels
      of RelA/NFkB, miR-146a, miR-150 and miR-125b are decreased in striatum of R6/2
      mice, a mouse model of HD and in cell models of HD. In a cell model, this effect
      could be reversed by exogenous expression of chaperone like proteins HYPK and
      Hsp70. We conclude that (i) miR-125b and miR-150 target p53, which in turn
      regulates RelA/NFkB and miR-146a expressions; (ii) reduced miR-125b and miR-150
      expressions, increased p53 level and decreased RelA/NFkB and miR-146a expressions
      originate from mutant HTT (iii) p53 directly or indirectly regulates the
      expression of miR-146a. Our observation of interplay between transcription
      factors and miRNAs using HD cell model provides an important platform upon which
      further work is to be done to establish if such regulation plays any role in HD
      pathogenesis.

PMID- 21887329
TI  - Sustained negative BOLD response in human fMRI finger tapping task.
AB  - In this work, we investigated the sustained negative blood oxygen level-dependent
      (BOLD) response (sNBR) using functional magnetic resonance imaging during a
      finger tapping task. We observed that the sNBR for this task was more extensive
      than has previously been reported. The cortical regions involved in sNBR are
      divided into the following three groups: frontal, somatosensory and occipital. By
      investigating the spatial structure, area, amplitude, and dynamics of the sNBR in
      comparison with those of its positive BOLD response (PBR) counterpart, we made
      the following observations. First, among the three groups, the somatosensory
      group contained the greatest number of activated voxels and the fewest
      deactivated voxels. In addition, the amplitude of the sNBR in this group was the
      smallest among the three groups. Second, the onset and peak time of the sNBR are
      both larger than those of the PBR, whereas the falling edge time of the sNBR is
      less than that of the PBR. Third, the long distance between most sNBR foci and
      their corresponding PBR foci makes it unlikely that they share the same blood
      supply artery. Fourth, the couplings between the sNBR and its PBR counterpart are
      distinct among different regions and thus should be investigated separately.
      These findings imply that the origin of most sNBR foci in the finger-tapping task
      is much more likely to be neuronal activity suppression rather than "blood
      steal."

PMID- 21887330
TI  - Mothers matter too: benefits of temperature oviposition preferences in newts.
AB  - The maternal manipulation hypothesis states that ectothermic females modify
      thermal conditions during embryonic development to benefit their offspring
      (anticipatory maternal effect). However, the recent theory suggests that the
      ultimate currency of an adaptive maternal effect is female fitness that can be
      maximized also by decreasing mean fitness of individual offspring. We evaluated
      benefits of temperature oviposition preferences in Alpine newts (Ichthyosaura
      [formerly Triturus] alpestris) by comparing the thermal sensitivity of maternal
      and offspring traits across a range of preferred oviposition temperatures (12,
      17, and 22 degrees C) and by manipulating the egg-predation risk during
      oviposition in a laboratory thermal gradient (12-22 degrees C). All traits showed
      varying responses to oviposition temperatures. Embryonic developmental rates
      increased with oviposition temperature, whereas hatchling size and swimming
      capacity showed the opposite pattern. Maternal oviposition and egg-predation
      rates were highest at the intermediate temperature. In the thermal gradient,
      females oviposited at the same temperature despite the presence of caged egg
      predators, water beetles (Agabus bipustulatus). We conclude that female newts
      prefer a particular temperature for egg-deposition to maximize their oviposition
      performance rather than offspring fitness. The evolution of advanced reproductive
      modes, such as prolonged egg-retention and viviparity, may require, among others,
      the transition from selfish temperature preferences for ovipositon to the
      anticipatory maternal effect.

PMID- 21887331
TI  - Overexpression of the HIF hydroxylases PHD1, PHD2, PHD3 and FIH are individually
      and collectively unfavorable prognosticators for NSCLC survival.
AB  - INTRODUCTION: Hypoxia induced factors (HIFs) are at the heart of the adaptive
      mechanisms cancer cells must implement for survival. HIFs are regulated by four
      hydroxylases; Prolyl hydroxylase (PHD)-1,-2,-3 and factor inhibiting HIF (FIH).
      We aimed to investigate the prognostic impact of these oxygen sensors in NSCLC.
      METHODS: Tumor tissue samples from 335 resected stages I to IIIA NSCLC patients
      was obtained and tissue microarrays (TMAs) were constructed. Hydroxylase
      expression was evaluated by immunohistochemistry. PRINCIPAL FINDINGS: There was
      scorable expression for all HIF hydroxylases in tumor cells, but not in stroma.
      In univariate analyses, high tumor cell expression of all the HIF hydroxylases
      were unfavorable prognosticators for disease-specific survival (DSS); PHD1 (P =
      0.023), PHD2 (P = 0.013), PHD3 (P = 0.018) and FIH (P = 0.033). In the
      multivariate analyses we found high tumor cell expression of PHD2 (HR = 2.03, CI
      95% 1.20-3.42, P = 0.008) and PHD1 (HR = 1.45, CI 95% 1.01-2.10, P = 0.047) to be
      significant independent prognosticators for DSS. Besides, there was an additive
      prognostic effect by the increasing number of highly expressed HIF hydroxylases.
      Provided none high expression HIF hydroxylases, the 5-year survival was 80% vs.
      23% if all four were highly expressed (HR = 6.48, CI 95% 2.23-18.8, P = 0.001).
      CONCLUSIONS: HIF hydroxylases are, in general, poor prognosticators for NSCLC
      survival. PHD1 and PHD2 are independent negative prognostic factors in NSCLC.
      Moreover, there is an additive poor prognostic impact by an increasing number of
      highly expressed HIF hydroxylases.

PMID- 21887332
TI  - Loss of cytoplasmic CDK1 predicts poor survival in human lung cancer and confers
      chemotherapeutic resistance.
AB  - The dismal lethality of lung cancer is due to late stage at diagnosis and
      inherent therapeutic resistance. The incorporation of targeted therapies has
      modestly improved clinical outcomes, but the identification of new targets could
      further improve clinical outcomes by guiding stratification of poor-risk early
      stage patients and individualizing therapeutic choices. We hypothesized that a
      sequential, combined microarray approach would be valuable to identify and
      validate new targets in lung cancer. We profiled gene expression signatures
      during lung epithelial cell immortalization and transformation, and showed that
      genes involved in mitosis were progressively enhanced in carcinogenesis. 28 genes
      were validated by immunoblotting and 4 genes were further evaluated in non-small
      cell lung cancer tissue microarrays. Although CDK1 was highly expressed in tumor
      tissues, its loss from the cytoplasm unexpectedly predicted poor survival and
      conferred resistance to chemotherapy in multiple cell lines, especially
      microtubule-directed agents. An analysis of expression of CDK1 and CDK1
      associated genes in the NCI60 cell line database confirmed the broad association
      of these genes with chemotherapeutic responsiveness. These results have
      implications for personalizing lung cancer therapy and highlight the potential of
      combined approaches for biomarker discovery.

PMID- 21887333
TI  - Aconitase regulation of erythropoiesis correlates with a novel licensing function
      in erythropoietin-induced ERK signaling.
AB  - BACKGROUND: Erythroid development requires the action of erythropoietin (EPO) on
      committed progenitors to match red cell output to demand. In this process, iron
      acts as a critical cofactor, with iron deficiency blunting EPO-responsiveness of
      erythroid progenitors. Aconitase enzymes have recently been identified as
      possible signal integration elements that couple erythropoiesis with iron
      availability. In the current study, a regulatory role for aconitase during
      erythropoiesis was ascertained using a direct inhibitory strategy.
      METHODOLOGY/PRINCIPAL FINDINGS: In C57BL/6 mice, infusion of an aconitase active
      site inhibitor caused a hypoplastic anemia and suppressed responsiveness to
      hemolytic challenge. In a murine model of polycythemia vera, aconitase inhibition
      rapidly normalized red cell counts, but did not perturb other lineages. In
      primary erythroid progenitor cultures, aconitase inhibition impaired
      proliferation and maturation but had no effect on viability or ATP levels. This
      inhibition correlated with a blockade in EPO signal transmission specifically via
      ERK, with preservation of JAK2-STAT5 and Akt activation. Correspondingly, a
      physical interaction between ERK and mitochondrial aconitase was identified and
      found to be sensitive to aconitase inhibition. CONCLUSIONS/SIGNIFICANCE: Direct
      aconitase inhibition interferes with erythropoiesis in vivo and in vitro,
      confirming a lineage-selective regulatory role involving its enzymatic activity.
      This inhibition spares metabolic function but impedes EPO-induced ERK signaling
      and disturbs a newly identified ERK-aconitase physical interaction. We propose a
      model in which aconitase functions as a licensing factor in ERK-dependent
      proliferation and differentiation, thereby providing a regulatory input for iron
      in EPO-dependent erythropoiesis. Directly targeting aconitase may provide an
      alternative to phlebotomy in the treatment of polycythemia vera.

PMID- 21887334
TI  - Oral and fecal Campylobacter concisus strains perturb barrier function by
      apoptosis induction in HT-29/B6 intestinal epithelial cells.
AB  - Campylobacter concisus infections of the gastrointestinal tract can be
      accompanied by diarrhea and inflammation, whereas colonization of the human oral
      cavity might have a commensal nature. We focus on the pathophysiology of C.
      concisus and the effects of different clinical oral and fecal C. concisus strains
      on human HT-29/B6 colon cells. Six oral and eight fecal strains of C. concisus
      were isolated. Mucus-producing HT-29/B6 epithelial monolayers were infected with
      the C. concisus strains. Transepithelial electrical resistance (R(t)) and tracer
      fluxes of different molecule size were measured in Ussing chambers. Tight
      junction (TJ) protein expression was determined by Western blotting, and
      subcellular TJ distribution was analyzed by confocal laser-scanning microscopy.
      Apoptosis induction was examined by TUNEL-staining and Western blot of caspase-3
      activation. All strains invaded confluent HT-29/B6 cells and impaired epithelial
      barrier function, characterized by a time- and dose-dependent decrease in R(t)
      either after infection from the apical side but even more from the basolateral
      compartment. TJ protein expression changes were sparse, only in apoptotic areas
      of infected monolayers TJ proteins were redistributed. Solely the barrier-forming
      TJ protein claudin-5 showed a reduced expression level to 66+/-8% (P<0.05), by
      expression regulation from the gene. Concomitantly, Lactate dehydrogenase release
      was elevated to 3.1+/-0.3% versus 0.7+/-0.1% in control (P<0.001), suggesting
      cytotoxic effects. Furthermore, oral and fecal C. concisus strains elevated
      apoptotic events to 5-fold. C. concisus-infected monolayers revealed an increased
      permeability for 332 Da fluorescein (1.74+/-0.13 vs. 0.56+/-0.17 10(-6) cm/s in
      control, P<0.05) but showed no difference in permeability for 4 kDa FITC-dextran
      (FD-4). The same was true in camptothecin-exposed monolayers, where camptothecin
      was used for apoptosis induction.In conclusion, epithelial barrier dysfunction by
      oral and fecal C. concisus strains could mainly be assigned to apoptotic leaks
      together with moderate TJ changes, demonstrating a leak-flux mechanism that
      parallels the clinical manifestation of diarrhea.

PMID- 21887336
TI  - Enhancing biomedical text summarization using semantic relation extraction.
AB  - Automatic text summarization for a biomedical concept can help researchers to get
      the key points of a certain topic from large amount of biomedical literature
      efficiently. In this paper, we present a method for generating text summary for a
      given biomedical concept, e.g., H1N1 disease, from multiple documents based on
      semantic relation extraction. Our approach includes three stages: 1) We extract
      semantic relations in each sentence using the semantic knowledge representation
      tool SemRep. 2) We develop a relation-level retrieval method to select the
      relations most relevant to each query concept and visualize them in a graphic
      representation. 3) For relations in the relevant set, we extract informative
      sentences that can interpret them from the document collection to generate text
      summary using an information retrieval based method. Our major focus in this work
      is to investigate the contribution of semantic relation extraction to the task of
      biomedical text summarization. The experimental results on summarization for a
      set of diseases show that the introduction of semantic knowledge improves the
      performance and our results are better than the MEAD system, a well-known tool
      for text summarization.

PMID- 21887335
TI  - The effect of ACACB cis-variants on gene expression and metabolic traits.
AB  - BACKGROUND: Acetyl Coenzyme A carboxylase beta (ACACB) is the rate-limiting
      enzyme in fatty acid oxidation, and continuous fatty acid oxidation in Acacb
      knock-out mice increases insulin sensitivity. Systematic human studies have not
      been performed to evaluate whether ACACB variants regulate gene expression and
      insulin sensitivity in skeletal muscle and adipose tissues. We sought to
      determine whether ACACB transcribed variants were associated with ACACB gene
      expression and insulin sensitivity in non-diabetic African American (AA) and
      European American (EA) adults. METHODS: ACACB transcribed single nucleotide
      polymorphisms (SNPs) were genotyped in 105 EAs and 46 AAs whose body mass index
      (BMI), lipid profiles and ACACB gene expression in subcutaneous adipose and
      skeletal muscle had been measured. Allelic expression imbalance (AEI) was
      assessed in lymphoblast cell lines from heterozygous subjects in an additional EA
      sample (n = 95). Selected SNPs were further examined for association with insulin
      sensitivity in a cohort of 417 EAs and 153 AAs. RESULTS: ACACB transcribed SNP
      rs2075260 (A/G) was associated with adipose ACACB messenger RNA expression in EAs
      and AAs (p = 3.8*10(-5), dominant model in meta-analysis, Stouffer method), with
      the (A) allele representing lower gene expression in adipose and higher insulin
      sensitivity in EAs (p = 0.04). In EAs, adipose ACACB expression was negatively
      associated with age and sex-adjusted BMI (r = -0.35, p = 0.0002). CONCLUSIONS:
      Common variants within the ACACB locus appear to regulate adipose gene expression
      in humans. Body fat (represented by BMI) may further regulate adipose ACACB gene
      expression in the EA population.

PMID- 21887337
TI  - Differential subcellular localization of the splice variants of the zinc
      transporter ZnT5 is dictated by the different C-terminal regions.
AB  - BACKGROUND: Zinc is emerging as an important intracellular signaling molecule, as
      well as fulfilling essential structural and catalytic functions through
      incorporation in a myriad of zinc metalloproteins so it is important to elucidate
      the molecular mechanisms of zinc homeostasis, including the subcellular
      localizations of zinc transporters. PRINCIPAL FINDINGS: Two splice variants of
      the human SLC30A5 Zn transporter gene (ZnT5) have been reported in the
      literature. These variants differ at their N- and C-terminal regions,
      corresponding with the use of different 5' and 3' exons. We demonstrate that full
      length human ZnT5 variant B is a genuine transcript in human intestinal cells and
      confirm expression of both variant A and variant B in a range of untreated human
      tissues by splice variant-specific RT-PCR. Using N- or C-terminal GFP or FLAG
      fusions of both isoforms of ZnT5 we identify that the differential subcellular
      localization to the Golgi apparatus and ER respectively is a function of their
      alternative C-terminal sequences. These different C-terminal regions result from
      the incorporation into the mature transcript of either the whole of exon 14
      (variant B) or only the 5' region of exon 14 plus exons 15-17 (variant A).
      CONCLUSIONS: We thus propose that exons 15 to 17 include a signal that results in
      trafficking of ZnT5 to the Golgi apparatus and that the 3' end of exon 14
      includes a signal that leads to retention in the ER.

PMID- 21887338
TI  - Shift in the intrinsic excitability of medial prefrontal cortex neurons following
      training in impulse control and cued-responding tasks.
AB  - Impulse control is an executive process that allows animals to inhibit their
      actions until an appropriate time. Previously, we reported that learning a simple
      response inhibition task increases AMPA currents at excitatory synapses in the
      prelimbic region of the medial prefrontal cortex (mPFC). Here, we examined
      whether modifications to intrinsic excitability occurred alongside the synaptic
      changes. To that end, we trained rats to obtain a food reward in a response
      inhibition task by withhold responding on a lever until they were signaled to
      respond. We then measured excitability, using whole-cell patch clamp recordings
      in brain slices, by quantifying action potentials generated by the injection of
      depolarizing current steps. Training in this task depressed the excitability of
      layer V pyramidal neurons of the prelimbic, but not infralimbic, region of the
      mPFC relative to behavioral controls. This decrease in maximum spiking frequency
      was significantly correlated with performance on the final session of the task.
      This change in intrinsic excitability may represent a homeostatic mechanism
      counterbalancing increased excitatory synaptic inputs onto those neurons in
      trained rats. Interestingly, subjects trained with a cue that predicted imminent
      reward availability had increased excitability in infralimbic, but not the
      prelimbic, pyramidal neurons. This dissociation suggests that both prelimbic and
      infralimbic neurons are involved in directing action, but specialized for
      different types of information, inhibitory or anticipatory, respectively.

PMID- 21887339
TI  - The chemotherapeutic drug 5-fluorouracil promotes PKR-mediated apoptosis in a p53
      independent manner in colon and breast cancer cells.
AB  - The chemotherapeutic drug 5-FU is widely used in the treatment of a range of
      cancers, but resistance to the drug remains a major clinical problem. Since
      defects in the mediators of apoptosis may account for chemo-resistance, the
      identification of new targets involved in 5-FU-induced apoptosis is of main
      clinical interest. We have identified the ds-RNA-dependent protein kinase (PKR)
      as a key molecular target of 5-FU involved in apoptosis induction in human colon
      and breast cancer cell lines. PKR distribution and activation, apoptosis
      induction and cytotoxic effects were analyzed during 5-FU and 5-FU/IFNalpha
      treatment in several colon and breast cancer cell lines with different p53
      status. PKR protein was activated by 5-FU treatment in a p53-independent manner,
      inducing phosphorylation of the protein synthesis translation initiation factor
      eIF-2alpha and cell death by apoptosis. Furthermore, PKR interference promoted a
      decreased response to 5-FU treatment and those cells were not affected by the
      synergistic antitumor activity of 5-FU/IFNalpha combination. These results, taken
      together, provide evidence that PKR is a key molecular target of 5-FU with
      potential relevance in the clinical use of this drug.

PMID- 21887340
TI  - Polybrene inhibits human mesenchymal stem cell proliferation during lentiviral
      transduction.
AB  - Human mesenchymal stem cells (hMSCs) can be engineered to express specific genes,
      either for their use in cell-based therapies or to track them in vivo over long
      periods of time. To obtain long-term expression of these genes, a lentivirus- or
      retrovirus-mediated cell transduction is often used. However, given that the
      efficiency with these viruses is typically low in primary cells, additives such
      as polybrene are always used for efficient viral transduction. Unfortunately, as
      presented here, exposure to polybrene alone at commonly used concentratons (1-8
      ug/mL) negatively impacts hMSC proliferation in a dose-dependent manner as
      measured by CyQUANT, EdU incorporation, and cell cycle analysis. This inhibition
      of proliferation was observable in culture even 3 weeks after exposure. Culturing
      the cells in the presence of FGF-2, a potent mitogen, did not abrogate this
      negative effect of polybrene. In fact, the normally sharp increase in hMSC
      proliferation that occurs during the first days of exposure to FGF-2 was absent
      at 4 ug/mL or higher concentrations of polybrene. Similarly, the effect of
      stimulating cell proliferation under simulated hypoxic conditions was also
      decreased when cells were exposed to polybrene, though overall proliferation
      rates were higher. The negative influence of polybrene was, however, reduced when
      the cells were exposed to polybrene for a shorter period of time (6 hr vs 24 hr).
      Thus, careful evaluation should be done when using polybrene to aid in lentiviral
      transduction of human MSCs or other primary cells, especially when cell number is
      critical.

PMID- 21887341
TI  - Inverse association between methylation of human papillomavirus type 16 DNA and
      risk of cervical intraepithelial neoplasia grades 2 or 3.
AB  - BACKGROUND: The clinical relevance of human papillomavirus type 16 (HPV16) DNA
      methylation has not been well documented, although its role in modulation of
      viral transcription is recognized. METHODS: Study subjects were 211 women
      attending Planned Parenthood clinics in Western Washington for routine
      Papanicolaou screening who were HPV16 positive at the screening and/or subsequent
      colposcopy visit. Methylation of 11 CpG dinucleotides in the 3' end of the long
      control region of the HPV16 genome was examined by sequencing the cloned
      polymerase chain reaction products. The association between risk of CIN2/3 and
      degree of CpG methylation was estimated using a logistic regression model.
      RESULTS: CIN2/3 was histologically confirmed in 94 (44.5%) of 211 HPV16 positive
      women. The likelihood of being diagnosed as CIN2/3 increased significantly with
      decreasing numbers of methylated CpGs (meCpGs) in the 3' end of the long control
      region (P(for trend) = 0.003). After adjusting for HPV16 variants, number of
      HPV16-positive visits, current smoking status and lifetime number of male sex
      partners, the odds ratio for the association of CIN2/3 with >=4 meCpGs was 0.31
      (95% confidence interval, 0.12-0.79). The proportion of >=4 meCpGs decreased
      appreciably as the severity of the cervical lesion increased (P(for trend) =
      0.001). The inverse association remained similar when CIN3 was used as the
      clinical endpoint. Although not statistically significant, the >=4 meCpGs-related
      risk reduction was more substantial among current, as compared to noncurrent,
      smokers. CONCLUSION: Results suggest that degree of the viral genome methylation
      is related to the outcome of an HPV16 cervical infection.

PMID- 21887343
TI  - Global and local features of semantic networks: evidence from the Hebrew mental
      lexicon.
AB  - BACKGROUND: Semantic memory has generated much research. As such, the majority of
      investigations have focused on the English language, and much less on other
      languages, such as Hebrew. Furthermore, little research has been done on search
      processes within the semantic network, even though they are abundant within
      cognitive semantic phenomena. METHODOLOGY/PRINCIPAL FINDINGS: We examine a unique
      dataset of free association norms to a set of target words and make use of
      correlation and network theory methodologies to investigate the global and local
      features of the Hebrew lexicon. The global features of the lexicon are
      investigated through the use of association correlations--correlations between
      target words, based on their association responses similarity; the local features
      of the lexicon are investigated through the use of association dependencies--the
      influence words have in the network on other words. CONCLUSIONS/SIGNIFICANCE: Our
      investigation uncovered Small-World Network features of the Hebrew lexicon,
      specifically a high clustering coefficient and a scale-free distribution, and
      provides means to examine how words group together into semantically related
      'free categories'. Our novel approach enables us to identify how words facilitate
      or inhibit the spread of activation within the network, and how these words
      influence each other. We discuss how these properties relate to classical
      research on spreading activation and suggest that these properties influence
      cognitive semantic search processes. A semantic search task, the Remote
      Association Test is discussed in light of our findings.

PMID- 21887342
TI  - Sphingosine kinase 1 and sphingosine 1-phosphate receptor 3 are functionally
      upregulated on astrocytes under pro-inflammatory conditions.
AB  - BACKGROUND: Reactive astrocytes are implicated in the development and maintenance
      of neuroinflammation in the demyelinating disease multiple sclerosis (MS). The
      sphingosine kinase 1 (SphK1)/sphingosine1-phosphate (S1P) receptor signaling
      pathway is involved in modulation of the inflammatory response in many cell
      types, but the role of S1P receptor subtype 3 (S1P(3)) signaling and SphK1 in
      activated rat astrocytes has not been defined. METHODOLOGY/PRINCIPAL FINDINGS:
      Using immunohistochemistry we observed the upregulation of S1P(3) and SphK1
      expression on reactive astrocytes and SphK1 on macrophages in MS lesions.
      Increased mRNA and protein expression of S1P(3) and SphK1, as measured by qPCR
      and Western blotting respectively, was observed after treatment of rat primary
      astrocyte cultures with the pro-inflammatory stimulus lipopolysaccharide (LPS).
      Activation of SphK by LPS stimulation was confirmed by SphK activity assay and
      was blocked by the use of the SphK inhibitor SKI (2-(p-hydroxyanilino)-4-(p
      chlorphenyl) thiazole. Treatment of astrocytes with a selective S1P(3) agonist
      led to increased phosphorylation of extracellular signal-regulated kinase (ERK)
      1/2), which was further elevated with a LPS pre-challenge, suggesting that S1P(3)
      upregulation can lead to increased functionality. Moreover, astrocyte migration
      in a scratch assay was induced by S1P and LPS and this LPS-induced migration was
      sensitive to inhibition of SphK1, and independent of cell proliferation. In
      addition, S1P induced secretion of the potentially neuroprotective chemokine
      CXCL1, which was increased when astrocytes were pre-challenged with LPS. A more
      prominent role of S1P(3) signaling compared to S1P(1) signaling was demonstrated
      by the use of selective S1P(3) or S1P(1) agonists. CONCLUSION/SIGNIFICANCE: In
      summary, our data demonstrate that the SphK1/S1P(3) signaling axis is upregulated
      when astrocytes are activated by LPS. This signaling pathway appears to play a
      role in the establishment and maintenance of astrocyte activation. Upregulation
      of the pathway in MS may be detrimental, e.g. through enhancing astrogliosis, or
      beneficial through increased remyelination via CXCL1.

PMID- 21887344
TI  - Identification and characterization of peripheral T-cell lymphoma-associated
      SEREX antigens.
AB  - Peripheral T-cell lymphomas (PTCL) are generally less common and pursue a more
      aggressive clinical course than B-cell lymphomas, with the T-cell phenotype
      itself being a poor prognostic factor in adult non-Hodgkin lymphoma (NHL). With
      notable exceptions such as ALK(+) anaplastic large cell lymphoma (ALCL, ALK+),
      the molecular abnormalities in PTCL remain poorly characterised. We had
      previously identified circulating antibodies to ALK in patients with ALCL,
      ALK(+). Thus, as a strategy to identify potential antigens associated with the
      pathogenesis of PTCL, not otherwise specified (PTCL, NOS), we screened a testis
      cDNA library with sera from four PTCL, NOS patients using the SEREX (serological
      analysis of recombinant cDNA expression libraries) technique. We identified nine
      PTCL, NOS-associated antigens whose immunological reactivity was further
      investigated using sera from 52 B- and T-cell lymphoma patients and 17 normal
      controls. The centrosomal protein CEP250 was specifically recognised by patients
      sera and showed increased protein expression in cell lines derived from T-cell
      versus B-cell malignancies. TCEB3, BECN1, and two previously uncharacterised
      proteins, c14orf93 and ZBTB44, were preferentially recognised by patients' sera.
      Transcripts for all nine genes were identified in 39 cancer cell lines and the
      five genes encoding preferentially lymphoma-recognised antigens were widely
      expressed in normal tissues and mononuclear cell subsets. In summary, this study
      identifies novel molecules that are immunologically recognised in vivo by
      patients with PTCL, NOS. Future studies are needed to determine whether these
      tumor antigens play a role in the pathogenesis of PTCL.

PMID- 21887345
TI  - Triceps surae short latency stretch reflexes contribute to ankle stiffness
      regulation during human running.
AB  - During human running, short latency stretch reflexes (SLRs) are elicited in the
      triceps surae muscles, but the function of these responses is still a matter of
      controversy. As the SLR is primarily mediated by Ia afferent nerve fibres,
      various methods have been used to examine SLR function by selectively blocking
      the Ia pathway in seated, standing and walking paradigms, but stretch reflex
      function has not been examined in detail during running. The purpose of this
      study was to examine triceps surae SLR function at different running speeds using
      Achilles tendon vibration to modify SLR size. Ten healthy participants ran on an
      instrumented treadmill at speeds between 7 and 15 km/h under 2 Achilles tendon
      vibration conditions: no vibration and 90 Hz vibration. Surface EMG from the
      triceps surae and tibialis anterior muscles, and 3D lower limb kinematics and
      ground reaction forces were simultaneously collected. In response to vibration,
      the SLR was depressed in the triceps surae muscles at all speeds. This coincided
      with short-lasting yielding at the ankle joint at speeds between 7 and 12 km/h,
      suggesting that the SLR contributes to muscle stiffness regulation by minimising
      ankle yielding during the early contact phase of running. Furthermore, at the
      fastest speed of 15 km/h, the SLR was still depressed by vibration in all muscles
      but yielding was no longer evident. This finding suggests that the SLR has
      greater functional importance at slow to intermediate running speeds than at
      faster speeds.

PMID- 21887346
TI  - SMURF1 amplification promotes invasiveness in pancreatic cancer.
AB  - Pancreatic cancer is a deadly disease, and new therapeutic targets are urgently
      needed. We previously identified DNA amplification at 7q21-q22 in pancreatic
      cancer cell lines. Now, by high-resolution genomic profiling of human pancreatic
      cancer cell lines and human tumors (engrafted in immunodeficient mice to enrich
      the cancer epithelial fraction), we define a 325 Kb minimal amplicon spanning
      SMURF1, an E3 ubiquitin ligase and known negative regulator of transforming
      growth factor beta (TGFbeta) growth inhibitory signaling. SMURF1 amplification
      was confirmed in primary human pancreatic cancers by fluorescence in situ
      hybridization (FISH), where 4 of 95 cases (4.2%) exhibited amplification. By RNA
      interference (RNAi), knockdown of SMURF1 in a human pancreatic cancer line with
      focal amplification (AsPC-1) did not alter cell growth, but led to reduced cell
      invasion and anchorage-independent growth. Interestingly, this effect was not
      mediated through altered TGFbeta signaling, assayed by transcriptional reporter.
      Finally, overexpression of SMURF1 (but not a catalytic mutant) led to loss of
      contact inhibition in NIH-3T3 mouse embryo fibroblast cells. Together, these
      findings identify SMURF1 as an amplified oncogene driving multiple tumorigenic
      phenotypes in pancreatic cancer, and provide a new druggable target for
      molecularly directed therapy.

PMID- 21887347
TI  - Early second-trimester serum miRNA profiling predicts gestational diabetes
      mellitus.
AB  - BACKGROUND: Gestational diabetes mellitus (GDM) is one type of diabetes that
      presents during pregnancy and significantly increases the risk of a number of
      adverse consequences for the fetus and mother. The microRNAs (miRNA) have
      recently been demonstrated to abundantly and stably exist in serum and to be
      potentially disease-specific. However, no reported study investigates the
      associations between serum miRNA and GDM. METHODOLOGY/PRINCIPAL FINDINGS: We
      systematically used the TaqMan Low Density Array followed by individual
      quantitative reverse transcription polymerase chain reaction assays to screen
      miRNAs in serum collected at 16-19 gestational weeks. The expression levels of
      three miRNAs (miR-132, miR-29a and miR-222) were significantly decreased in GDM
      women with respect to the controls in similar gestational weeks in our discovery
      evaluation and internal validation, and two miRNAs (miR-29a and miR-222) were
      also consistently validated in two-centric external validation sample sets. In
      addition, the knockdown of miR-29a could increase Insulin-induced gene 1 (Insig1)
      expression level and subsequently the level of Phosphoenolpyruvate Carboxy
      Kinase2 (PCK2) in HepG2 cell lines. CONCLUSIONS/SIGNIFICANCE: Serum miRNAs are
      differentially expressed between GDM women and controls and could be candidate
      biomarkers for predicting GDM. The utility of miR-29a, miR-222 and miR-132 as
      serum-based non-invasive biomarkers warrants further evaluation and optimization.

PMID- 21887348
TI  - Tailored beta-cyclodextrin blocks the translocation pores of binary exotoxins
      from C. botulinum and C. perfringens and protects cells from intoxication.
AB  - BACKGROUND: Clostridium botulinum C2 toxin and Clostridium perfringens iota toxin
      are binary exotoxins, which ADP-ribosylate actin in the cytosol of mammalian
      cells and thereby destroy the cytoskeleton. C2 and iota toxin consists of two
      individual proteins, an enzymatic active (A-) component and a separate receptor
      binding and translocation (B-) component. The latter forms a complex with the A
      component on the surface of target cells and after receptor-mediated endocytosis,
      it mediates the translocation of the A-component from acidified endosomal
      vesicles into the cytosol. To this end, the B-components form heptameric pores in
      endosomal membranes, which serve as translocation channels for the A-components.
      METHODOLOGY/PRINCIPAL FINDINGS: Here we demonstrate that a 7-fold symmetrical
      positively charged beta-cyclodextrin derivative, per-6-S-(3
      aminomethyl)benzylthio-beta-cyclodextrin, protects cultured cells from
      intoxication with C2 and iota toxins in a concentration-dependent manner starting
      at low micromolar concentrations. We discovered that the compound inhibited the
      pH-dependent membrane translocation of the A-components of both toxins in intact
      cells. Consistently, the compound strongly blocked transmembrane channels formed
      by the B-components of C2 and iota toxin in planar lipid bilayers in vitro. With
      C2 toxin, we consecutively ruled out all other possible inhibitory mechanisms
      showing that the compound did not interfere with the binding of the toxin to the
      cells or with the enzyme activity of the A-component. CONCLUSIONS/SIGNIFICANCE:
      The described beta-cyclodextrin derivative was previously identified as one of
      the most potent inhibitors of the binary lethal toxin of Bacillus anthracis both
      in vitro and in vivo, implying that it might represent a broad-spectrum inhibitor
      of binary pore-forming exotoxins from pathogenic bacteria.

PMID- 21887349
TI  - Diversity in the architecture of ATLs, a family of plant ubiquitin-ligases, leads
      to recognition and targeting of substrates in different cellular environments.
AB  - Ubiquitin-ligases or E3s are components of the ubiquitin proteasome system (UPS)
      that coordinate the transfer of ubiquitin to the target protein. A major class of
      ubiquitin-ligases consists of RING-finger domain proteins that include the
      substrate recognition sequences in the same polypeptide; these are known as
      single-subunit RING finger E3s. We are studying a particular family of RING
      finger E3s, named ATL, that contain a transmembrane domain and the RING-H2 finger
      domain; none of the member of the family contains any other previously described
      domain. Although the study of a few members in A. thaliana and O. sativa has been
      reported, the role of this family in the life cycle of a plant is still vague. To
      provide tools to advance on the functional analysis of this family we have
      undertaken a phylogenetic analysis of ATLs in twenty-four plant genomes. ATLs
      were found in all the 24 plant species analyzed, in numbers ranging from 20-28 in
      two basal species to 162 in soybean. Analysis of ATLs arrayed in tandem indicates
      that sets of genes are expanding in a species-specific manner. To get insights
      into the domain architecture of ATLs we generated 75 pHMM LOGOs from 1815 ATLs,
      and unraveled potential protein-protein interaction regions by means of yeast two
      hybrid assays. Several ATLs were found to interact with DSK2a/ubiquilin through a
      region at the amino-terminal end, suggesting that this is a widespread
      interaction that may assist in the mode of action of ATLs; the region was traced
      to a distinct sequence LOGO. Our analysis provides significant observations on
      the evolution and expansion of the ATL family in addition to information on the
      domain structure of this class of ubiquitin-ligases that may be involved in plant
      adaptation to environmental stress.

PMID- 21887350
TI  - Early presymptomatic and long-term changes of rest activity cycles and cognitive
      behavior in a MPTP-monkey model of Parkinson's disease.
AB  - BACKGROUND: It is increasingly recognized that non-motor symptoms are a prominent
      feature of Parkinson's disease and in the case of cognitive deficits can precede
      onset of the characteristic motor symptoms. Here, we examine in 4 monkeys
      chronically treated with low doses of the neurotoxin MPTP the early and long-term
      alterations of rest-activity rhythms in relationship to the appearance of motor
      and cognitive symptoms. METHODOLOGY/PRINCIPAL FINDINGS: Behavioral activity
      recordings as well as motor and cognitive assessments were carried out
      continuously and in parallel before, during and for several months following MPTP
      treatment (12-56 weeks). Cognitive abilities were assessed using a task that is
      dependent on the functional integrity of the fronto-striatal axis. Rest-activity
      cycles were monitored continuously using infrared movement detectors of locomotor
      activity. Motor impairment was evaluated using standardized scales for primates.
      Results show that MPTP treatment led to an immediate alteration (within one week)
      of rest-activity cycles and cognitive deficits. Parkinsonian motor deficits only
      became apparent 3 to 5 weeks after initiating chronic MPTP administration. In
      three of the four animals studied, clinical scores returned to control levels 5-7
      weeks following cessation of MPTP treatment. In contrast, both cognitive deficits
      and chronobiological alterations persisted for many months. Levodopa treatment
      led to an improvement of cognitive performance but did not affect rest-activity
      rhythms in the two cases tested. CONCLUSIONS/SIGNIFICANCE: Present results show
      that i) changes in the rest activity cycles constituted early detectable
      consequences of MPTP treatment and, along with cognitive alterations,
      characterize the presymptomatic stage; ii) following motor recovery there is a
      long-term persistence of non-motor symptoms that could reflect differential
      underlying compensatory mechanisms in these domains; iii) the progressive MPTP
      monkey model of presymptomatic ongoing parkinsonism offers possibilities for in
      depth studies of early non-motor symptoms including sleep alterations and
      cognitive deficits.

PMID- 21887351
TI  - Community regulation: the relative importance of recruitment and predation
      intensity of an intertidal community dominant in a seascape context.
AB  - Predicting the strength and context-dependency of species interactions across
      multiple scales is a core area in ecology. This is especially challenging in the
      marine environment, where populations of most predators and prey are generally
      open, because of their pelagic larval phase, and recruitment of both is highly
      variable. In this study we use a comparative-experimental approach on small and
      large spatial scales to test the relationship between predation intensity and
      prey recruitment and their relative importance in shaping populations of a
      dominant rocky intertidal space occupier, mussels, in the context of seascape
      (availability of nearby subtidal reef habitat). Predation intensity on
      transplanted mussels was tested inside and outside cages and recruitment was
      measured with standard larval settlement collectors. We found that on intertidal
      rocky benches with contiguous subtidal reefs in New Zealand, mussel larval
      recruitment is usually low but predation on recruits by subtidal consumers (fish,
      crabs) is intense during high tide. On nearby intertidal rocky benches with
      adjacent sandy subtidal habitats, larval recruitment is usually greater but
      subtidal predators are typically rare and predation is weaker. Multiple
      regression analysis showed that predation intensity accounts for most of the
      variability in the abundance of adult mussels compared to recruitment. This
      seascape-dependent, predation-recruitment relationship could scale up to explain
      regional community variability. We argue that community ecology models should
      include seascape context-dependency and its effects on recruitment and species
      interactions for better predictions of coastal community dynamics and structure.

PMID- 21887352
TI  - Impact of load-related neural processes on feature binding in visuospatial
      working memory.
AB  - BACKGROUND: The capacity of visual working memory (WM) is substantially limited
      and only a fraction of what we see is maintained as a temporary trace. The
      process of binding visual features has been proposed as an adaptive means of
      minimising information demands on WM. However the neural mechanisms underlying
      this process, and its modulation by task and load effects, are not well
      understood. OBJECTIVE: To investigate the neural correlates of feature binding
      and its modulation by WM load during the sequential phases of encoding,
      maintenance and retrieval. METHODS AND FINDINGS: 18 young healthy participants
      performed a visuospatial WM task with independent factors of load and feature
      conjunction (object identity and position) in an event-related functional MRI
      study. During stimulus encoding, load-invariant conjunction-related activity was
      observed in left prefrontal cortex and left hippocampus. During maintenance,
      greater activity for task demands of feature conjunction versus single features,
      and for increased load was observed in left-sided regions of the superior
      occipital cortex, precuneus and superior frontal cortex. Where these effects were
      expressed in overlapping cortical regions, their combined effect was additive.
      During retrieval, however, an interaction of load and feature conjunction was
      observed. This modulation of feature conjunction activity under increased load
      was expressed through greater deactivation in medial structures identified as
      part of the default mode network. CONCLUSIONS AND SIGNIFICANCE: The relationship
      between memory load and feature binding qualitatively differed through each phase
      of the WM task. Of particular interest was the interaction of these factors
      observed within regions of the default mode network during retrieval which we
      interpret as suggesting that at low loads, binding processes may be 'automatic'
      but at higher loads it becomes a resource-intensive process leading to
      disengagement of activity in this network. These findings provide new insights
      into how feature binding operates within the capacity-limited WM system.

PMID- 21887353
TI  - In vivo emergence of HIV-1 highly sensitive to neutralizing antibodies.
AB  - BACKGROUND: The rapid and continual viral escape from neutralizing antibodies is
      well documented in HIV-1 infection. Here we report in vivo emergence of viruses
      with heightened sensitivity to neutralizing antibodies, sometimes paralleling the
      development of neutralization escape. METHODOLOGY/PRINCIPAL FINDINGS: Sequential
      viral envs were amplified from seven HIV-1 infected men monitored from
      seroconversion up to 5 years after infection. Env-recombinant infectious
      molecular clones were generated and tested for coreceptor use, macrophage tropism
      and neutralization sensitivity to homologous and heterologous serum, soluble CD4
      and monoclonal antibodies IgG1b12, 2G12 and 17b. We found that HIV-1 evolves
      sensitivity to contemporaneous neutralizing antibodies during infection.
      Neutralization sensitive viruses grow out even when potent autologous
      neutralizing antibodies are present in patient serum. Increased sensitivity to
      neutralization was associated with susceptibility of the CD4 binding site or
      epitopes induced after CD4 binding, and mediated by complex envelope determinants
      including V3 and V4 residues. The development of neutralization sensitive viruses
      occurred without clinical progression, coreceptor switch or change in tropism for
      primary macrophages. CONCLUSIONS: We propose that an interplay of selective
      forces for greater virus replication efficiency without the need to resist
      neutralizing antibodies in a compartment protected from immune surveillance may
      explain the temporal course described here for the in vivo emergence of HIV-1
      isolates with high sensitivity to neutralizing antibodies.

PMID- 21887354
TI  - Apelin deficiency accelerates the progression of amyotrophic lateral sclerosis.
AB  - Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized
      by the selective loss of motor neurons. Recent studies have implicated that
      chronic hypoxia and insufficient vascular endothelial growth factor (VEGF)
      dependent neuroprotection may lead to the degeneration of motor neurons in ALS.
      Expression of apelin, an endogenous ligand for the G protein-coupled receptor
      APJ, is regulated by hypoxia. In addition, recent reports suggest that apelin
      protects neurons against glutamate-induced excitotoxicity. Here, we examined
      whether apelin is an endogenous neuroprotective factor using SOD1(G93A) mouse
      model of ALS. In mouse CNS tissues, the highest expressions of both apelin and
      APJ mRNAs were detected in spinal cord. APJ immunoreactivity was observed in
      neuronal cell bodies located in gray matter of spinal cord. Although apelin mRNA
      expression in the spinal cord of wild-type mice was not changed from 4 to 18
      weeks age, that of SOD1(G93A) mice was reduced along with the paralytic
      phenotype. In addition, double mutant apelin-deficient and SOD1(G93A) displayed
      the disease phenotypes earlier than SOD1(G93A) littermates. Immunohistochemical
      observation revealed that the number of motor neurons was decreased and microglia
      were activated in the spinal cord of the double mutant mice, indicating that
      apelin deficiency pathologically accelerated the progression of ALS. Furthermore,
      we showed that apelin enhanced the protective effect of VEGF on H(2)O(2)-induced
      neuronal death in primary neurons. These results suggest that apelin/APJ system
      in the spinal cord has a neuroprotective effect against the pathogenesis of ALS.

PMID- 21887355
TI  - Evidence of weak habitat specialisation in microscopic animals.
AB  - Macroecology and biogeography of microscopic organisms (any living organism
      smaller than 2 mm) are quickly developing into fruitful research areas.
      Microscopic organisms also offer the potential for testing predictions and models
      derived from observations on larger organisms due to the feasibility of
      performing lab and mesocosm experiments. However, more empirical knowledge on the
      similarities and differences between micro- and macro-organisms is needed to
      ascertain how much of the results obtained from the former can be generalised to
      the latter. One potential misconception, based mostly on anedoctal evidence
      rather than explicit tests, is that microscopic organisms may have wider
      ecological tolerance and a lower degree of habitat specialisation than large
      organisms. Here we explicitly test this hypothesis within the framework of
      metacommunity theory, by studying host specificify in the assemblages of bdelloid
      rotifers (animals about 350 um in body length) living in different species of
      lichens in Sweden. Using several regression-based and ANOVA analyses and
      controlling for both spatial structure and the kind of substrate the lichen grow
      over (bark vs rock), we found evidence of significant but weak species-specific
      associations between bdelloids and lichens, a wide overlap in species composition
      between lichens, and wide ecological tolerance for most bdelloid species. This
      confirms that microscopic organisms such as bdelloids have a lower degree of
      habitat specialisation than larger organisms, although this happens in a complex
      scenario of ecological processes, where source-sink dynamics and geographic
      distances seem to have no effect on species composition at the analysed scale.

PMID- 21887356
TI  - Chloroplast genome variation in upland and lowland switchgrass.
AB  - Switchgrass (Panicum virgatum L.) exists at multiple ploidies and two
      phenotypically distinct ecotypes. To facilitate interploidal comparisons and to
      understand the extent of sequence variation within existing breeding pools, two
      complete switchgrass chloroplast genomes were sequenced from individuals
      representative of the upland and lowland ecotypes. The results demonstrated a
      very high degree of conservation in gene content and order with other sequenced
      plastid genomes. The lowland ecotype reference sequence (Kanlow Lin1) was 139,677
      base pairs while the upland sequence (Summer Lin2) was 139,619 base pairs.
      Alignments between the lowland reference sequence and short-read sequence data
      from existing sequence datasets identified as either upland or lowland confirmed
      known polymorphisms and indicated the presence of other differences. Insertions
      and deletions principally occurred near stretches of homopolymer simple sequence
      repeats in intergenic regions while most Single Nucleotide Polymorphisms (SNPs)
      occurred in intergenic regions and introns within the single copy portions of the
      genome. The polymorphism rate between upland and lowland switchgrass ecotypes was
      found to be similar to rates reported between chloroplast genomes of indica and
      japonica subspecies of rice which were believed to have diverged 0.2-0.4 million
      years ago.

PMID- 21887357
TI  - Ketamine influences CLOCK:BMAL1 function leading to altered circadian gene
      expression.
AB  - Major mood disorders have been linked to abnormalities in circadian rhythms,
      leading to disturbances in sleep, mood, temperature, and hormonal levels. We
      provide evidence that ketamine, a drug with rapid antidepressant effects,
      influences the function of the circadian molecular machinery. Ketamine modulates
      CLOCK:BMAL1-mediated transcriptional activation when these regulators are
      ectopically expressed in NG108-15 neuronal cells. Inhibition occurs in a dose
      dependent manner and is attenuated after treatment with the GSK3beta antagonist
      SB21673. We analyzed the effect of ketamine on circadian gene expression and
      observed a dose-dependent reduction in the amplitude of circadian transcription
      of the Bmal1, Per2, and Cry1 genes. Finally, chromatin-immunoprecipitation
      analyses revealed that ketamine altered the recruitment of the CLOCK:BMAL1
      complex on circadian promoters in a time-dependent manner. Our results reveal a
      yet unsuspected molecular mode of action of ketamine and thereby may suggest
      possible pharmacological antidepressant strategies.

PMID- 21887358
TI  - Identification of a novel aminopeptidase P-like gene (OnAPP) possibly involved in
      Bt toxicity and resistance in a major corn pest (Ostrinia nubilalis).
AB  - Studies to understand the Bacillus thuringiensis (Bt) resistance mechanism in
      European corn borer (ECB, Ostrinia nubilalis) suggest that resistance may be due
      to changes in the midgut-specific Bt toxin receptor. In this study, we identified
      10 aminopeptidase-like genes, which have previously been identified as putative
      Bt toxin receptors in other insects and examined their expression in relation to
      Cry1Ab toxicity and resistance. Expression analysis for the 10 aminopeptidase
      like genes revealed that most of these genes were expressed predominantly in the
      larval midgut, but there was no difference in the expression of these genes in
      Cry1Ab resistant and susceptible strains. This suggested that altered expression
      of these genes was unlikely to be responsible for resistance in these ECB
      strains. However, we found that there were changes in two amino acid residues of
      the aminopeptidase-P like gene (OnAPP) involving Glu(305) to Lys(305) and
      Arg(307) to Leu(307) in the two Cry1Ab-resistant strains as compared with three
      Cry1Ab-susceptible strains. The mature OnAPP contains 682 amino acid residues and
      has a putative signal peptide at the N-terminus, a predicted glycosylphosphatidyl
      inositol (GPI)-anchor signal at the C-terminal, three predicted N-glycosylation
      sites at residues N178, N278 and N417, and an O-glycosylation site at residue
      T653. We used a feeding based-RNA interference assay to examine the role of the
      OnAPP gene in Cry1Ab toxicity and resistance. Bioassays of Cry1Ab in larvae fed
      diet containing OnAPP dsRNA resulted in a 38% reduction in the transcript level
      of OnAPP and a 25% reduction in the susceptibility to Cry1Ab as compared with
      larvae fed GFP dsRNA or water. These results strongly suggest that the OnAPP gene
      could be involved in binding the Cry1Ab toxin in the ECB larval midgut and that
      mutations in this gene may be associated with Bt resistance in these two ECB
      strains.

PMID- 21887359
TI  - Corals use similar immune cells and wound-healing processes as those of higher
      organisms.
AB  - Sessile animals, like corals, frequently suffer physical injury from a variety of
      sources, thus wound-healing mechanisms that restore tissue integrity and prevent
      infection are vitally important for defence. Despite the ecological importance of
      reef-building corals, little is known about the cells and processes involved in
      wound healing in this group or in phylogenetically basal metazoans in general. A
      histological investigation into wound healing of the scleractinian coral Porites
      cylindrica at 0 h, 6 h, 24 h and 48 h after injury revealed differences in
      cellular components between injured and healthy tissues. Cell counts of the
      obligate endosymbiont, Symbiodinium, and melanin volume fraction analysis
      revealed rapid declines in both Symbiodinium abundance and tissue cross-sectional
      area occupied by melanin-containing granular cells after injury. Four phases of
      wound healing were identified, which are similar to phases described for both
      vertebrates and invertebrates. The four phases included (i) plug formation via
      the degranulation of melanin-containing granular cells; (ii) immune cell
      infiltration (inflammation); (iii) granular tissue formation (proliferation); and
      (iv) maturation. This study provides detailed documentation of the processes
      involved in scleractinian wound healing for the first time and further elucidates
      the roles of previously-described immune cells, such as fibroblasts. These
      results demonstrate the conservation of wound healing processes from anthozoans
      to humans.

PMID- 21887360
TI  - Functional foveal splitting: evidence from neuropsychological and multimodal MRI
      investigations in a Chinese patient with a splenium lesion.
AB  - It remains controversial and hotly debated whether foveal information is double
      projected to both hemispheres or split at the midline between the two
      hemispheres. We investigated this issue in a unique patient with lesions in the
      splenium of the corpus callosum and the left medial occipitotemporal region,
      through a series of neuropsychological tests and multimodal MRI scans. Behavioral
      experiments showed that (1) the patient had difficulties in reading simple and
      compound Chinese characters when they were presented in the foveal but left to
      the fixation, (2) he failed to recognize the left component of compound
      characters when the compound characters were presented in the central foveal
      field, (3) his judgments of the gender of centrally presented chimeric faces were
      exclusively based on the left half-face and he was unaware that the faces were
      chimeric. Functional MRI data showed that Chinese characters, only when presented
      in the right foveal field but not in the left foveal field, activated a region in
      the left occipitotemporal sulcus in the mid-fusiform, which is recognized as
      visual word form area. Together with existing evidence in the literature, results
      of the current study suggest that the representation of foveal stimuli is
      functionally split at object processing levels.

PMID- 21887361
TI  - Intermittent hypoxia after transient focal ischemia induces hippocampal
      neurogenesis and c-Fos expression and reverses spatial memory deficits in rats.
AB  - BACKGROUND: Memory impairment is a frequent complication of brain ischemia.
      Neurogenesis is implicated in learning and memory and is regulated by the
      transcription factor c-Fos. Preconditioning intermittent hypoxia (IH) attenuates
      ischemia-related memory impairments, but it is not known whether post-ischemia IH
      intervention has a similar effect. We investigated the effects of post-ischemia
      IH on hippocampal neurogenesis and c-Fos expression as well as spatial learning
      and memory in rats. METHODOLOGY/PRINCIPAL FINDINGS: Focal cerebral ischemia was
      induced in some rats by middle cerebral artery occlusion (MCAO), while other rats
      received sham MCAO surgery. Beginning a week later, half of the rats of each
      group received IH interventions (12% oxygen concentration, 4 hrs/d, for 7 d) and
      half received sham IH sessions. An additional group of rats received MCAO, IH,
      and injections of the neurogenesis-impairing agent 3'-AZT. Spatial learning and
      memory was measured in the Morris water maze, and hippocampal neurogenesis and c
      Fos expression were examined. Hypoxia-inducible factor 1alpha (HIF-1alpha) and
      phosphorylated mitogen-activated protein kinase (pMAPK) were considered as
      possible mediators of IH-induced changes in neurogenesis and c-Fos expression. IH
      intervention following MCAO resulted in recovered spatial memory, increased
      hippocampal neurogenesis, and increased expression of c-Fos in newborn
      hippocampal cells. These effects were blocked by 3'-AZT. IH intervention
      following MCAO also was associated with increased hippocampal pMAPK and HIF
      1alpha expression. CONCLUSIONS/SIGNIFICANCE: IH intervention following MCAO
      rescued ischemia-induced spatial learning and memory impairments, likely by
      inducing hippocampal neurogenesis and c-Fos expression through mediators
      including pMAPK and HIF-1alpha.

PMID- 21887362
TI  - Magnetic-stimulation-related physiological artifacts in hemodynamic near-infrared
      spectroscopy signals.
AB  - Hemodynamic responses evoked by transcranial magnetic stimulation (TMS) can be
      measured with near-infrared spectroscopy (NIRS). This study demonstrates that
      cerebral neuronal activity is not their sole contributor. We compared bilateral
      NIRS responses following brain stimulation to those from the shoulders evoked by
      shoulder stimulation and contrasted them with changes in circulatory parameters.
      The left primary motor cortex of ten subjects was stimulated with 8-s repetitive
      TMS trains at 0.5, 1, and 2 Hz at an intensity of 75% of the resting motor
      threshold. Hemoglobin concentration changes were measured with NIRS on the
      stimulated and contralateral hemispheres. The photoplethysmograph (PPG) amplitude
      and heart rate were recorded as well. The left shoulder of ten other subjects was
      stimulated with the same protocol while the hemoglobin concentration changes in
      both shoulders were measured. In addition to PPG amplitude and heart rate, the
      pulse transit time was recorded. The brain stimulation reduced the total
      hemoglobin concentration (HbT) on the stimulated and contralateral hemispheres.
      The shoulder stimulation reduced HbT on the stimulated shoulder but increased it
      contralaterally. The waveforms of the HbT responses on the stimulated hemisphere
      and shoulder correlated strongly with each other (r = 0.65-0.87). All circulatory
      parameters were also affected. The results suggest that the TMS-evoked NIRS
      signal includes components that do not result directly from cerebral neuronal
      activity. These components arise from local effects of TMS on the vasculature.
      Also global circulatory effects due to arousal may affect the responses. Thus,
      studies involving TMS-evoked NIRS responses should be carefully controlled for
      physiological artifacts and effective artifact removal methods are needed to draw
      inferences about TMS-evoked brain activity.

PMID- 21887363
TI  - Heterogeneity in SDF-1 expression defines the vasculogenic potential of adult
      cardiac progenitor cells.
AB  - RATIONALE: The adult myocardium has been reported to harbor several classes of
      multipotent progenitor cells (CPCs) with tri-lineage differentiation potential.
      It is not clear whether c-kit+CPCs represent a uniform precursor population or a
      more complex mixture of cell types. OBJECTIVE: To characterize and understand
      vasculogenic heterogeneity within c-kit+presumptive cardiac progenitor cell
      populations. METHODS AND RESULTS: c-kit+, sca-1+ CPCs obtained from adult mouse
      left ventricle expressed stem cell-associated genes, including Oct-4 and Myc, and
      were self-renewing, pluripotent and clonogenic. Detailed single cell clonal
      analysis of 17 clones revealed that most (14/17) exhibited trilineage
      differentiation potential. However, striking morphological differences were
      observed among clones that were heritable and stable in long-term culture. 3
      major groups were identified: round (7/17), flat or spindle-shaped (5/17) and
      stellate (5/17). Stellate morphology was predictive of vasculogenic
      differentiation in Matrigel. Genome-wide expression studies and bioinformatic
      analysis revealed clonally stable, heritable differences in stromal cell-derived
      factor-1 (SDF-1) expression that correlated strongly with stellate morphology and
      vasculogenic capacity. Endogenous SDF-1 production contributed directly to
      vasculogenic differentiation: both shRNA-mediated knockdown of SDF-1 and AMD3100,
      an antagonist of the SDF-1 receptor CXC chemokine Receptor-4 (CXCR4), reduced
      tube-forming capacity, while exogenous SDF-1 induced tube formation by 2 non
      vasculogenic clones. CPCs producing SDF-1 were able to vascularize Matrigel
      dermal implants in vivo, while CPCs with low SDF-1 production were not.
      CONCLUSIONS: Clonogenic c-kit+, sca-1+ CPCs are heterogeneous in morphology, gene
      expression patterns and differentiation potential. Clone-specific levels of SDF-1
      expression both predict and promote development of a vasculogenic phenotype via a
      previously unreported autocrine mechanism.

PMID- 21887364
TI  - Comparative transcriptome analyses indicate molecular homology of zebrafish
      swimbladder and mammalian lung.
AB  - The fish swimbladder is a unique organ in vertebrate evolution and it functions
      for regulating buoyancy in most teleost species. It has long been postulated as a
      homolog of the tetrapod lung, but the molecular evidence is scarce. In order to
      understand the molecular function of swimbladder as well as its relationship with
      lungs in tetrapods, transcriptomic analyses of zebrafish swimbladder were carried
      out by RNA-seq. Gene ontology classification showed that genes in cytoskeleton
      and endoplasmic reticulum were enriched in the swimbladder. Further analyses
      depicted gene sets and pathways closely related to cytoskeleton constitution and
      regulation, cell adhesion, and extracellular matrix. Several prominent
      transcription factor genes in the swimbladder including hoxc4a, hoxc6a, hoxc8a
      and foxf1 were identified and their expressions in developing swimbladder during
      embryogenesis were confirmed. By comparison of enriched transcripts in the
      swimbladder with those in human and mouse lungs, we established the resemblance
      of transcriptome of the zebrafish swimbladder and mammalian lungs. Based on the
      transcriptomic data of zebrafish swimbladder, the predominant functions of
      swimbladder are in its epithelial and muscular tissues. Our comparative analyses
      also provide molecular evidence of the relatedness of the fish swimbladder and
      mammalian lung.

PMID- 21887365
TI  - Pathogenicity and rapid growth kinetics of feline immunodeficiency virus are
      linked to 3' elements.
AB  - Chimeric viruses constructed between a highly pathogenic Feline Immunodeficiency
      Virus isolate (FIV-C36) and a less pathogenic but neurotropic strain (FIV-PPR)
      have been used to map viral genetic determinants of in vivo pathogenicity.
      Chimeric virus FIV-PCenv, which contains FIV-C36 genome from the 3' region of pol
      to upstream of the 3'LTR on an FIV-PPR backbone, was previously shown to be
      replication-competent in vivo, inducing altered CD4(+) T-cell and neutrophil
      profiles intermediate between parental strains following a delay in viral
      replication during initial infection. Examination of FIV-PCenv proviral sequences
      recovered at week 11 post-infection revealed two changes compared to initial
      viral inoculum; the most significant being arginine to histidine in the integrase
      region of Pol at residue 813 (R813H). Pooled plasma from the initial in vivo
      study was used to inoculate a second cohort of cats to determine whether similar
      virulence and kinetics could be established following primary infection. Viral
      replication kinetics and immunocyte profiles were monitored in blood, bone
      marrow, and saliva over a one-year period. Passaged FIV-PCenv again displayed
      intermediate phenotype between parental strains, but unlike primary experiments,
      the onset of acute viremia was not delayed. CD4/8 alterations were noted in all
      groups of animals, though significant changes from controls were delayed in FIV
      PPR infected animals compared to FIV-C36 and FIV-PCenv. In vivo passage of FIV
      PCenv increased replication-competence relative to the initial molecularly-cloned
      chimera in association with one adaptive nucleotide change in the 5' end of the
      genome relative to primary tissue culture inoculum, while mutations in the 3' end
      of the genome were not detected. The results are consistent with the
      interpretation that 3' elements contribute to heightened virulence of FIV-C36,
      and that integrase residue 813 plays an important role in facilitating successful
      in vivo replication.

PMID- 21887366
TI  - Sodium/myo-Inositol transporters: substrate transport requirements and regional
      brain expression in the TgCRND8 mouse model of amyloid pathology.
AB  - Inositol stereoisomers, myo- and scyllo-inositol, are known to enter the brain
      and are significantly elevated following oral administration. Elevations in brain
      inositol levels occur across a concentration gradient as a result of active
      transport from the periphery. There are two sodium/myo-inositol transporters
      (SMIT1, SMIT2) that may be responsible for regulating brain inositol levels. The
      goals of this study were to determine the effects of aging and Alzheimer's
      disease (AD)-like amyloid pathology on transporter expression, to compare
      regional expression and to analyze substrate requirements of the inositol
      transporters. QPCR was used to examine expression of the two transporters in the
      cortex, hippocampus and cerebellum of TgCRND8 mice, a mouse model of amyloid
      pathology, in comparison to non-transgenic littermates. In addition, we examined
      the structural features of inositol required for active transport, utilizing a
      cell-based competitive uptake assay. Disease pathology did not alter transporter
      expression in the cortex or hippocampus (p>0.005), with only minimal effects of
      aging observed in the cerebellum (SMIT1: F(2,26) = 12.62; p = 0.0002; SMIT2:
      F(2,26) = 8.71; p = 0.0015). Overall, brain SMIT1 levels were higher than SMIT2,
      however, regional differences were observed. For SMIT1, at 4 and 6 months
      cerebellar SMIT1 levels were significantly higher than cortical and hippocampal
      levels (p<0.05). For SMIT2, at all three ages both cortical and cerebellar SMIT2
      levels were significantly higher than hippocampal levels (p<0.05) and at 4 and 6
      months of age, cerebellar SMIT2 levels were also significantly higher than
      cortical levels (p<0.05). Inositol transporter levels are stably expressed as a
      function of age, and expression is unaltered with disease pathology in the
      TgCRND8 mouse. Given the fact that scyllo-inositol is currently in clinical
      trials for the treatment of AD, the stable expression of inositol transporters
      regardless of disease pathology is an important finding.

PMID- 21887367
TI  - Intermittent screening and treatment versus intermittent preventive treatment of
      malaria in pregnancy: provider knowledge and acceptability.
AB  - Malaria in pregnancy (MiP) is associated with increased risks of maternal and
      foetal complications. The WHO recommends a package of interventions including
      intermittent preventive treatment (IPT) with sulphadoxine-pyrimethamine (SP),
      insecticide-treated nets and effective case management. However, with increasing
      SP resistance, the effectiveness of SP-IPT has been questioned. Intermittent
      screening and treatment (IST) has recently been shown in Ghana to be as
      efficacious as SP-IPT. This study investigates two important requirements for
      effective delivery of IST and SP-IPT: antenatal care (ANC) provider knowledge,
      and acceptance of the different strategies. Structured interviews with 134 ANC
      providers at 67 public health facilities in Ashanti Region, Ghana collected
      information on knowledge of the risks and preventative and curative interventions
      against MiP. Composite indicators of knowledge of SP-IPT, and case management of
      MiP were developed. Log binomial regression of predictors of provider knowledge
      was explored. Qualitative data were collected through in-depth interviews with
      fourteen ANC providers with some knowledge of IST to gain an indication of the
      factors influencing acceptance of the IST approach. 88.1% of providers knew all
      elements of the SP-IPT policy, compared to 20.1% and 41.8% who knew the treatment
      policy for malaria in the first or second/third trimesters, respectively.
      Workshop attendance was a univariate predictor of each knowledge indicator.
      Qualitative findings suggest preference for prevention over cure, and increased
      workload may be barriers to IST implementation. However, a change in strategy in
      the face of SP resistance is likely to be supported; health of pregnant women is
      a strong motivation for ANC provider practice. If IST was to be introduced as
      part of routine ANC activities, attention would need to be given to improving the
      knowledge and practices of ANC staff in relation to appropriate treatment of MiP.
      Health worker support for any MiP intervention delivered through ANC clinics is
      critical.

PMID- 21887368
TI  - Laforin, a dual specificity phosphatase involved in Lafora disease, is present
      mainly as monomeric form with full phosphatase activity.
AB  - Lafora Disease (LD) is a fatal neurodegenerative epileptic disorder that presents
      as a neurological deterioration with the accumulation of insoluble,
      intracellular, hyperphosphorylated carbohydrates called Lafora bodies (LBs). LD
      is caused by mutations in either the gene encoding laforin or malin. Laforin
      contains a dual specificity phosphatase domain and a carbohydrate-binding module,
      and is a member of the recently described family of glucan phosphatases. In the
      current study, we investigated the functional and physiological relevance of
      laforin dimerization. We purified recombinant human laforin and subjected the
      monomer and dimer fractions to denaturing gel electrophoresis, mass spectrometry,
      phosphatase assays, protein-protein interaction assays, and glucan binding
      assays. Our results demonstrate that laforin prevalently exists as a monomer with
      a small dimer fraction both in vitro and in vivo. Of mechanistic importance,
      laforin monomer and dimer possess equal phosphatase activity, and they both
      associate with malin and bind glucans to a similar extent. However, we found
      differences between the two states' ability to interact simultaneously with malin
      and carbohydrates. Furthermore, we tested other members of the glucan phosphatase
      family. Cumulatively, our data suggest that laforin monomer is the dominant form
      of the protein and that it contains phosphatase activity.

PMID- 21887369
TI  - IL-17A expression is localised to both mononuclear and polymorphonuclear synovial
      cell infiltrates.
AB  - INTRODUCTION: This study examines the expression of IL-17A-secreting cells within
      the inflamed synovium and the relationship to in vivo joint hypoxia measurements.
      METHODS: IL-17A expression was quantified in synovial tissue (ST), serum and
      synovial fluid (SF) by immunohistochemistry and MSD-plex assays. IL-6 SF and
      serum levels were measured by MSD-plex assays. Dual immunofluorescence for IL-17A
      was quantified in ST CD15+ cells (neutrophils), Tryptase+ (mast cells) and CD4+
      (T cells). Synovial tissue oxygen (tpO(2)) levels were measured under direct
      visualisation at arthroscopy. Synovial infiltration was assessed using
      immunohistochemistry for cell specific markers. Peripheral blood mononuclear and
      polymorphonuclear cells were isolated and exposed to normoxic or 3% hypoxic
      conditions. IL-17A and IL-6 were quantified as above in culture supernatants.
      RESULTS: IL-17A expression was localised to mononuclear and polymorphonuclear
      (PMN) cells in inflamed ST. Dual immunoflourescent staining co-localised IL-17A
      expression with CD15+ neutrophils Tryptase+ mast cells and CD4+T cells. % IL-17A
      positivity was highest on CD15+ neutrophils, followed by mast cells and then
      CD4+T-cells. The number of IL-17A-secreting PMN cells significantly correlated
      with sublining CD68 expression (r = 0.618, p<0.01). IL-17A SF levels correlated
      with IL-6 SF levels (r = 0.675, p<0.01). Patients categorized according to
      tp0(2)< or >20 mmHg, showed those with low tp0(2)<20 mmHg had significantly
      higher IL-17A+ mononuclear cells with no difference observed for PMNs. Exposure
      of mononuclear and polymorphonuclear cells to 3% hypoxia, significantly induced
      IL-6 in mononuclear cells, but had no effect on IL-17A expression in mononuclear
      and polymorphonuclear cells. CONCLUSION: This study demonstrates IL-17A
      expression is localised to several immune cell subtypes within the inflamed
      synovial tissue, further supporting the concept that IL-17A is a key mediator in
      inflammatory arthritis. The association of hypoxia with Il-17A expression appears
      to be indirect, probably through hypoxia-induced pro-inflammatory pathways and
      leukocyte influx within the joint microenvironment.

PMID- 21887370
TI  - Spatial frequency-based analysis of mean red blood cell speed in single
      microvessels: investigation of microvascular perfusion in rat cerebral cortex.
AB  - BACKGROUND: Our previous study has shown that prenatal exposure to X-ray
      irradiation causes cerebral hypo-perfusion during the postnatal development of
      central nervous system (CNS). However, the source of the hypo-perfusion and its
      impact on the CNS development remains unclear. The present study developed an
      automatic analysis method to determine the mean red blood cell (RBC) speed
      through single microvessels imaged with two-photon microscopy in the cerebral
      cortex of rats prenatally exposed to X-ray irradiation (1.5 Gy).
      METHODOLOGY/PRINCIPAL FINDINGS: We obtained a mean RBC speed (0.9+/-0.6 mm/sec)
      that ranged from 0.2 to 4.4 mm/sec from 121 vessels in the radiation-exposed
      rats, which was about 40% lower than that of normal rats that were not exposed.
      These results were then compared with the conventional method for monitoring
      microvascular perfusion using the arteriovenous transit time (AVTT) determined by
      tracking fluorescent markers. A significant increase in the AVTT was observed in
      the exposed rats (1.9+/-0.6 sec) as compared to the age-matched non-exposed rats
      (1.2+/-0.3 sec). The results indicate that parenchyma capillary blood velocity in
      the exposed rats was approximately 37% lower than in non-exposed rats.
      CONCLUSIONS/SIGNIFICANCE: The algorithm presented is simple and robust relative
      to monitoring individual RBC speeds, which is superior in terms of noise
      tolerance and computation time. The demonstrative results show that the method
      developed in this study for determining the mean RBC speed in the spatial
      frequency domain was consistent with the conventional transit time method.

PMID- 21887371
TI  - Variation in community structure across vertical intertidal stress gradients: how
      does it compare with horizontal variation at different scales?
AB  - In rocky intertidal habitats, the pronounced increase in environmental stress
      from low to high elevations greatly affects community structure, that is, the
      combined measure of species identity and their relative abundance. Recent studies
      have shown that ecological variation also occurs along the coastline at a variety
      of spatial scales. Little is known, however, on how vertical variation compares
      with horizontal variation measured at increasing spatial scales (in terms of
      sampling interval). Because broad-scale processes can generate geographical
      patterns in community structure, we tested the hypothesis that vertical
      ecological variation is higher than fine-scale horizontal variation but lower
      than broad-scale horizontal variation. To test this prediction, we compared the
      variation in community structure across intertidal elevations on rocky shores of
      Helgoland Island with independent estimates of horizontal variation measured at
      the scale of patches (quadrats separated by 10s of cm), sites (quadrats separated
      by a few m), and shores (quadrats separated by 100s to 1000s of m). The
      multivariate analyses done on community structure supported our prediction.
      Specifically, vertical variation was significantly higher than patch- and site
      scale horizontal variation but lower than shore-scale horizontal variation.
      Similar patterns were found for the variation in abundance of foundation taxa
      such as Fucus spp. and Mastocarpus stellatus, suggesting that the effects of
      these canopy-forming algae, known to function as ecosystem engineers, may explain
      part of the observed variability in community structure. Our findings suggest
      that broad-scale processes affecting species performance increase ecological
      variability relative to the pervasive fine-scale patchiness already described for
      marine coasts and the well known variation caused by vertical stress gradients.
      Our results also indicate that experimental research aiming to understand
      community structure on marine shores should benefit from applying a multi-scale
      approach.

PMID- 21887372
TI  - C-KIT signaling depends on microphthalmia-associated transcription factor for
      effects on cell proliferation.
AB  - The development of melanocytes is regulated by the tyrosine kinase receptor c-KIT
      and the basic-helix-loop-helix-leucine zipper transcription factor Mitf. These
      essential melanocyte survival regulators are also well known oncogenic factors in
      malignant melanoma. Despite their importance, not much is known about the
      regulatory mechanisms and signaling pathways involved. In this study, we
      therefore sought to identify the signaling pathways and mechanisms involved in c
      KIT mediated regulation of Mitf. We report that c-KIT stimulation leads to the
      activation of Mitf specifically through the c-KIT phosphorylation sites Y721 (PI3
      kinase binding site), Y568 and Y570 (Src binding site). Our study not only
      confirms the involvement of Ras-Erk signaling pathway in the activation of Mitf,
      but also establishes that Src kinase binding to Y568 and Y570 of c-KIT is
      required. Using specific inhibitors we observe and verify that c-KIT induced
      activation of Mitf is dependent on PI3-, Akt-, Src-, p38- or Mek kinases.
      Moreover, the proliferative effect of c-KIT is dependent on Mitf in HEK293T
      cells. In contrast, c-KIT Y568F and Y721F mutants are less effective in driving
      cell proliferation, compared to wild type c-KIT. Our results reveal novel
      mechanisms by which c-KIT signaling regulates Mitf, with implications for
      understanding both melanocyte development and melanoma.

PMID- 21887373
TI  - Salinity gradient of the Baltic Sea limits the reproduction and population
      expansion of the newly invaded comb jelly Mnemiopsis leidyi.
AB  - The recent invasion of the comb jelly Mnemiopsis leidyi into northern European
      waters is of major public and scientific concern. One of the key features making
      M. leidyi a successful invader is its high fecundity combined with fast growth
      rates. However, little is known about physiological limitations to its
      reproduction and consequent possible abiotic restrictions to its dispersal. To
      evaluate the invasion potential of M. leidyi into the brackish Baltic Sea we
      studied in situ egg production rates in different regions and at different
      salinities in the laboratory, representing the salinity gradient of the Baltic
      Sea. During October 2009 M. leidyi actively reproduced over large areas of the
      Baltic Sea. Egg production rates scaled with animal size but decreased
      significantly with decreasing salinity, both in the field (7-29) and in
      laboratory experiments (6-33). Temperature and zooplankton, i.e. food abundance,
      could not explain the observed differences. Reproduction rates at conditions
      representing the Kattegat, south western and central Baltic Sea, respectively,
      were 2.8 fold higher at the highest salinities (33 and 25) than at intermediate
      salinities (10 and 15) and 21 times higher compared from intermediate to the
      lowest salinity tested (6). Higher salinity areas such as the Kattegat, and to a
      lower extent the south western Baltic, seem to act as source regions for the M.
      leidyi population in the central Baltic Sea where a self-sustaining population,
      due to the low salinity, cannot be maintained.

PMID- 21887374
TI  - Fatty acid and peptide profiles in plasma membrane and membrane rafts of PUFA
      supplemented RAW264.7 macrophages.
AB  - The eukaryotic cell membrane possesses numerous complex functions, which are
      essential for life. At this, the composition and the structure of the lipid
      bilayer are of particular importance. Polyunsaturated fatty acids may modulate
      the physical properties of biological membranes via alteration of membrane lipid
      composition affecting numerous physiological processes, e.g. in the immune
      system. In this systematic study we present fatty acid and peptide profiles of
      cell membrane and membrane rafts of murine macrophages that have been
      supplemented with saturated fatty acids as well as PUFAs from the n-3, the n-6
      and the n-9 family. Using fatty acid composition analysis and mass spectrometry
      based peptidome profiling we found that PUFAs from both the n-3 and the n-6
      family have an impact on lipid and protein composition of plasma membrane and
      membrane rafts in a similar manner. In addition, we found a relation between the
      number of bis-allyl-methylene positions of the PUFA added and the unsaturation
      index of plasma membrane as well as membrane rafts of supplemented cells. With
      regard to the proposed significance of lipid microdomains for disease development
      and treatment our study will help to achieve a targeted dietary modulation of
      immune cell lipid bilayers.

PMID- 21887375
TI  - Identification and characterization of alternative promoters, transcripts and
      protein isoforms of zebrafish R2 gene.
AB  - Ribonucleotide reductase (RNR) is the rate-limiting enzyme in the de novo
      synthesis of deoxyribonucleoside triphosphates. Expression of RNR subunits is
      closely associated with DNA replication and repair. Mammalian RNR M2 subunit (R2)
      functions exclusively in DNA replication of normal cells due to its S phase
      specific expression and late mitotic degradation. Herein, we demonstrate the
      control of R2 expression through alternative promoters, splicing and
      polyadenylation sites in zebrafish. Three functional R2 promoters were identified
      to generate six transcript variants with distinct 5' termini. The proximal
      promoter contains a conserved E2F binding site and two CCAAT boxes, which are
      crucial for the transcription of R2 gene during cell cycle. Activity of the
      distal promoter can be induced by DNA damage to generate four transcript variants
      through alternative splicing. In addition, two novel splice variants were found
      to encode distinct N-truncated R2 isoforms containing residues for enzymatic
      activity but no KEN box essential for its proteolysis. These two N-truncated R2
      isoforms remained in the cytoplasm and were able to interact with RNR M1 subunit
      (R1). Thus, our results suggest that multilayered mechanisms control the
      differential expression and function of zebrafish R2 gene during cell cycle and
      under genotoxic stress.

PMID- 21887376
TI  - Is nitric oxide decrease observed with naphthoquinones in LPS stimulated RAW
      264.7 macrophages a beneficial property?
AB  - The search of new anti-inflammatory drugs has been a current preoccupation, due
      to the need of effective drugs, with less adverse reactions than those used
      nowadays. Several naphthoquinones (plumbagin, naphthazarin, juglone, menadione,
      diosquinone and 1,4-naphthoquinone), plus p-hydroquinone and p-benzoquinone were
      evaluated for their ability to cause a reduction of nitric oxide (NO) production,
      when RAW 264.7 macrophages were stimulated with lipopolysaccharide (LPS).
      Dexamethasone was used as positive control. Among the tested compounds,
      diosquinone was the only one that caused a NO reduction with statistical
      importance and without cytotoxicity: an IC(25) of 1.09+/-0.24 uM was found, with
      38.25+/-6.50% (p<0.001) NO reduction at 1.5 uM. In order to elucidate if this NO
      decrease resulted from the interference of diosquinone with cellular defence
      mechanisms against LPS or to its conversion into peroxynitrite, by reaction with
      superoxide radical formed by naphthoquinones redox cycling, 3-nitrotyrosine and
      superoxide determination was also performed. None of these parameters showed
      significant changes relative to control. Furthermore, diosquinone caused a
      decrease in the pro-inflammatory cytokines: tumour necrosis factor-alpha (TNF
      alpha) and interleukin 6 (IL-6). Therefore, according to the results obtained,
      diosquinone, studied for its anti-inflammatory potential for the first time
      herein, has beneficial effects in inflammation control. This study enlightens the
      mechanisms of action of naphthoquinones in inflammatory models, by checking for
      the first time the contribution of oxidative stress generated by naphthoquinones
      to NO reduction.

PMID- 21887377
TI  - Identification of a phosphorylation-dependent nuclear localization motif in
      interferon regulatory factor 2 binding protein 2.
AB  - BACKGROUND: Interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a
      muscle-enriched transcription factor required to activate vascular endothelial
      growth factor-A (VEGFA) expression in muscle. IRF2BP2 is found in the nucleus of
      cardiac and skeletal muscle cells. During the process of skeletal muscle
      differentiation, some IRF2BP2 becomes relocated to the cytoplasm, although the
      functional significance of this relocation and the mechanisms that control
      nucleocytoplasmic localization of IRF2BP2 are not yet known.
      METHODOLOGY/PRINCIPAL FINDINGS: Here, by fusing IRF2BP2 to green fluorescent
      protein and testing a series of deletion and site-directed mutagenesis
      constructs, we mapped the nuclear localization signal (NLS) to an evolutionarily
      conserved sequence (354)ARKRKPSP(361) in IRF2BP2. This sequence corresponds to a
      classical nuclear localization motif bearing positively charged arginine and
      lysine residues. Substitution of arginine and lysine with negatively charged
      aspartic acid residues blocked nuclear localization. However, these residues were
      not sufficient because nuclear targeting of IRF2BP2 also required phosphorylation
      of serine 360 (S360). Many large-scale phosphopeptide proteomic studies had
      reported previously that serine 360 of IRF2BP2 is phosphorylated in numerous
      human cell types. Alanine substitution at this site abolished IRF2BP2 nuclear
      localization in C(2)C(12) myoblasts and CV1 cells. In contrast, substituting
      serine 360 with aspartic acid forced nuclear retention and prevented cytoplasmic
      redistribution in differentiated C(2)C(12) muscle cells. As for the effects of
      these mutations on VEGFA promoter activity, the S360A mutation interfered with
      VEGFA activation, as expected. Surprisingly, the S360D mutation also interfered
      with VEGFA activation, suggesting that this mutation, while enforcing nuclear
      entry, may disrupt an essential activation function of IRF2BP2.
      CONCLUSIONS/SIGNIFICANCE: Nuclear localization of IRF2BP2 depends on
      phosphorylation near a conserved NLS. Changes in phosphorylation status likely
      control nucleocytoplasmic localization of IRF2BP2 during muscle differentiation.

PMID- 21887378
TI  - Tissue-specific Salmonella Typhimurium gene expression during persistence in
      pigs.
AB  - Salmonellosis caused by Salmonella Typhimurium is one of the most important
      bacterial zoonotic diseases. The bacterium persists in pigs resulting in
      asymptomatic 'carrier pigs', generating a major source for Salmonella
      contamination of pork. Until now, very little is known concerning the mechanisms
      used by Salmonella Typhimurium during persistence in pigs. Using in vivo
      expression technology (IVET), a promoter-trap method based on DeltapurA
      attenuation of the parent strain, we identified 37 Salmonella Typhimurium genes
      that were expressed 3 weeks post oral inoculation in the tonsils, ileum and
      ileocaecal lymph nodes of pigs. Several genes were expressed in all three
      analyzed organs, while other genes were only expressed in one or two organs.
      Subsequently, the identified IVET transformants were pooled and reintroduced in
      pigs to detect tissue-specific gene expression patterns. We found that efp and
      rpoZ were specifically expressed in the ileocaecal lymph nodes during Salmonella
      peristence in pigs. Furthermore, we compared the persistence ability of
      substitution mutants for the IVET-identified genes sifB and STM4067 to that of
      the wild type in a mixed infection model. The DeltaSTM4067::kanR was
      significantly attenuated in the ileum contents, caecum and caecum contents and
      faeces of pigs 3 weeks post inoculation, while deletion of the SPI-2 effector
      gene sifB did not affect Salmonella Typhimurium persistence. Although our list of
      identified genes is not exhaustive, we found that efp and rpoZ were specifically
      expressed in the ileocaecal lymph nodes of pigs and we identified STM4067 as a
      factor involved in Salmonella persistence in pigs. To our knowledge, our study is
      the first to identify Salmonella Typhimurium genes expressed during persistence
      in pigs.

PMID- 21887380
TI  - RssAB signaling coordinates early development of surface multicellularity in
      Serratia marcescens.
AB  - Bacteria can coordinate several multicellular behaviors in response to
      environmental changes. Among these, swarming and biofilm formation have attracted
      significant attention for their correlation with bacterial pathogenicity.
      However, little is known about when and where the signaling occurs to trigger
      either swarming or biofilm formation. We have previously identified an RssAB two
      component system involved in the regulation of swarming motility and biofilm
      formation in Serratia marcescens. Here we monitored the RssAB signaling status
      within single cells by tracing the location of the translational fusion protein
      EGFP-RssB following development of swarming or biofilm formation. RssAB signaling
      is specifically activated before surface migration in swarming development and
      during the early stage of biofilm formation. The activation results in the
      release of RssB from its cognate inner membrane sensor kinase, RssA, to the
      cytoplasm where the downstream gene promoters are located. Such dynamic
      localization of RssB requires phosphorylation of this regulator. By revealing the
      temporal activation of RssAB signaling following development of surface
      multicellular behavior, our findings contribute to an improved understanding of
      how bacteria coordinate their lifestyle on a surface.

PMID- 21887379
TI  - Myosin IIb activity and phosphorylation status determines dendritic spine and
      post-synaptic density morphology.
AB  - Dendritic spines in hippocampal neurons mature from a filopodia-like precursor
      into a mushroom-shape with an enlarged post-synaptic density (PSD) and serve as
      the primary post-synaptic location of the excitatory neurotransmission that
      underlies learning and memory. Using myosin II regulatory mutants, inhibitors,
      and knockdowns, we show that non-muscle myosin IIB (MIIB) activity determines
      where spines form and whether they persist as filopodia-like spine precursors or
      mature into a mushroom-shape. MIIB also determines PSD size, morphology, and
      placement in the spine. Local inactivation of MIIB leads to the formation of
      filopodia-like spine protrusions from the dendritic shaft. However, di
      phosphorylation of the regulatory light chain on residues Thr18 and Ser19 by Rho
      kinase is required for spine maturation. Inhibition of MIIB activity or a mono
      phosphomimetic mutant of RLC similarly prevented maturation even in the presence
      of NMDA receptor activation. Expression of an actin cross-linking, non
      contractile mutant, MIIB R709C, showed that maturation into a mushroom-shape
      requires contractile activity. Loss of MIIB also leads to an elongated PSD
      morphology that is no longer restricted to the spine tip; whereas increased MIIB
      activity, specifically through RLC-T18, S19 di-phosphorylation, increases PSD
      area. These observations support a model whereby myosin II inactivation forms
      filopodia-like protrusions that only mature once NMDA receptor activation
      increases RLC di-phosphorylation to stimulate MIIB contractility, resulting in
      mushroom-shaped spines with an enlarged PSD.

PMID- 21887381
TI  - Electrophysiological properties of embryonic stem cell-derived neurons.
AB  - In vitro generation of functional neurons from embryonic stem (ES) cells and
      induced pluripotent stem cells offers exciting opportunities for dissecting gene
      function, disease modelling, and therapeutic drug screening. To realize the
      potential of stem cells in these biomedical applications, a complete
      understanding of the cell models of interest is required. While rapid advances
      have been made in developing the technologies for directed induction of defined
      neuronal subtypes, most published works focus on the molecular characterization
      of the derived neural cultures. To characterize the functional properties of
      these neural cultures, we utilized an ES cell model that gave rise to neurons
      expressing the green fluorescent protein (GFP) and conducted targeted whole-cell
      electrophysiological recordings from ES cell-derived neurons. Current-clamp
      recordings revealed that most neurons could fire single overshooting action
      potentials; in some cases multiple action potentials could be evoked by
      depolarization, or occurred spontaneously. Voltage-clamp recordings revealed that
      neurons exhibited neuronal-like currents, including an outward current typical of
      a delayed rectifier potassium conductance and a fast-activating, fast
      inactivating inward current, typical of a sodium conductance. Taken together,
      these results indicate that ES cell-derived GFP(+) neurons in culture display
      functional neuronal properties even at early stages of differentiation.

PMID- 21887382
TI  - Multisensory integration and attention in autism spectrum disorder: evidence from
      event-related potentials.
AB  - Successful integration of various simultaneously perceived perceptual signals is
      crucial for social behavior. Recent findings indicate that this multisensory
      integration (MSI) can be modulated by attention. Theories of Autism Spectrum
      Disorders (ASDs) suggest that MSI is affected in this population while it remains
      unclear to what extent this is related to impairments in attentional capacity. In
      the present study Event-related potentials (ERPs) following emotionally congruent
      and incongruent face-voice pairs were measured in 23 high-functioning, adult ASD
      individuals and 24 age- and IQ-matched controls. MSI was studied while the
      attention of the participants was manipulated. ERPs were measured at typical
      auditory and visual processing peaks, namely, P2 and N170. While controls showed
      MSI during divided attention and easy selective attention tasks, individuals with
      ASD showed MSI during easy selective attention tasks only. It was concluded that
      individuals with ASD are able to process multisensory emotional stimuli, but this
      is differently modulated by attention mechanisms in these participants,
      especially those associated with divided attention. This atypical interaction
      between attention and MSI is also relevant to treatment strategies, with training
      of multisensory attentional control possibly being more beneficial than
      conventional sensory integration therapy.

PMID- 21887383
TI  - An FXPRLamide neuropeptide induces seasonal reproductive polyphenism underlying a
      life-history tradeoff in the tussock moth.
AB  - The white spotted tussock moth, Orgyia thyellina, is a typical insect that
      exhibits seasonal polyphenisms in morphological, physiological, and behavioral
      traits, including a life-history tradeoff known as oogenesis-flight syndrome.
      However, the developmental processes and molecular mechanisms that mediate
      developmental plasticity, including life-history tradeoff, remain largely
      unknown. To analyze the molecular mechanisms involved in reproductive
      polyphenism, including the diapause induction, we first cloned and characterized
      the diapause hormone-pheromone biosynthesis activating neuropeptide (DH-PBAN)
      cDNA encoding the five Phe-X-Pro-Arg-Leu-NH(2) (FXPRLa) neuropeptides: DH, PBAN,
      and alpha-, beta-, and gamma-SGNPs (subesophageal ganglion neuropeptides). This
      gene is expressed in neurosecretory cells within the subesophageal ganglion whose
      axonal projections reach the neurohemal organ, the corpus cardiacum, suggesting
      that the DH neuroendocrine system is conserved in Lepidoptera. By injection of
      chemically synthetic DH and anti-FXPRLa antibody into female pupae, we revealed
      that not only does the Orgyia DH induce embryonic diapause, but also that this
      neuropeptide induces seasonal polyphenism, participating in the hypertrophy of
      follicles and ovaries. In addition, the other four FXPRLa also induced embryonic
      diapause in O. thyellina, but not in Bombyx mori. This is the first study showing
      that a neuropeptide has a pleiotropic effect in seasonal reproductive polyphenism
      to accomplish seasonal adaptation. We also show that a novel factor (i.e., the DH
      neuropeptide) acts as an important inducer of seasonal polyphenism underlying a
      life-history tradeoff. Furthermore, we speculate that there must be evolutionary
      conservation and diversification in the neuroendocrine systems of two
      lepidopteran genera, Orgyia and Bombyx, in order to facilitate the evolution of
      coregulated life-history traits and tradeoffs.

PMID- 21887384
TI  - Conditioning individual mosquitoes to an odor: sex, source, and time.
AB  - Olfactory conditioning of mosquitoes may have important implications for vector
      pathogen-host dynamics. If mosquitoes learn about specific host attributes
      associated with pathogen infection, it may help to explain the heterogeneity of
      biting and disease patterns observed in the field. Sugar-feeding is a requirement
      for survival in both male and female mosquitoes. It provides a starting point for
      learning research in mosquitoes that avoids the confounding factors associated
      with the observer being a potential blood-host and has the capability to address
      certain areas of close-range mosquito learning behavior that have not previously
      been described. This study was designed to investigate the ability of the
      southern house mosquito, Culex quinquefasciatus Say to associate odor with a
      sugar-meal with emphasis on important experimental considerations of mosquito age
      (1.2 d old and 3-5 d old), sex (male and female), source (laboratory and wild),
      and the time between conditioning and testing (<5 min, 1 hr, 2.5 hr, 5 hr, 10 hr,
      and 24 hr). Mosquitoes were individually conditioned to an odor across these
      different experimental conditions. Details of the conditioning protocol are
      presented as well as the use of binary logistic regression to analyze the complex
      dataset generated from this experimental design. The results suggest that each of
      the experimental factors may be important in different ways. Both the source of
      the mosquitoes and sex of the mosquitoes had significant effects on conditioned
      responses. The largest effect on conditioning was observed in the lack of
      positive response following conditioning for females aged 3-5 d derived from a
      long established colony. Overall, this study provides a method for conditioning
      experiments involving individual mosquitoes at close range and provides for
      future discussion of the relevance and broader questions that can be asked of
      olfactory conditioning in mosquitoes.

PMID- 21887385
TI  - Arctigenin efficiently enhanced sedentary mice treadmill endurance.
AB  - Physical inactivity is considered as one of the potential risk factors for the
      development of type 2 diabetes and other metabolic diseases, while endurance
      exercise training could enhance fat oxidation that is associated with insulin
      sensitivity improvement in obesity. AMP-activated protein kinase (AMPK) as an
      energy sensor plays pivotal roles in the regulation of energy homeostasis, and
      its activation could improve glucose uptake, promote mitochondrial biogenesis and
      increase glycolysis. Recent research has even suggested that AMPK activation
      contributed to endurance enhancement without exercise. Here we report that the
      natural product arctigenin from the traditional herb Arctium lappa L.
      (Compositae) strongly increased AMPK phosphorylation and subsequently up
      regulated its downstream pathway in both H9C2 and C2C12 cells. It was discovered
      that arctigenin phosphorylated AMPK via calmodulin-dependent protein kinase
      kinase (CaMKK) and serine/threonine kinase 11(LKB1)-dependent pathways. Mice
      treadmill based in vivo assay further indicated that administration of arctigenin
      improved efficiently mice endurance as reflected by the increased fatigue time
      and distance, and potently enhanced mitochondrial biogenesis and fatty acid
      oxidation (FAO) related genes expression in muscle tissues. Our results thus
      suggested that arctigenin might be used as a potential lead compound for the
      discovery of the agents with mimic exercise training effects to treat metabolic
      diseases.

PMID- 21887386
TI  - Efficient differentiation of embryonic stem cells into hepatic cells in vitro
      using a feeder-free basement membrane substratum.
AB  - The endoderm-inducing effect of the mesoderm-derived supportive cell line M15 on
      embryonic stem (ES) cells is partly mediated through the extracellular matrix, of
      which laminin alpha5 is a crucial component. Mouse ES or induced pluripotent stem
      cells cultured on a synthesized basement membrane (sBM) substratum, using an
      HEK293 cell line (rLN10-293 cell) stably expressing laminin-511, could
      differentiate into definitive endoderm and subsequently into pancreatic lineages.
      In this study, we investigated the differentiation on sBM of mouse and human ES
      cells into hepatic lineages. The results indicated that the BM components played
      an important role in supporting the regional-specific differentiation of ES cells
      into hepatic endoderm. We show here that knockdown of integrin beta1 (Itgb1) in
      ES cells reduced their differentiation into hepatic lineages and that this is
      mediated through Akt signaling activation. Moreover, under optimal conditions,
      human ES cells differentiated to express mature hepatocyte markers and secreted
      high levels of albumin. This novel procedure for inducing hepatic differentiation
      will be useful for elucidating the molecular mechanisms controlling lineage
      specific fates during gut regionalization. It could also represent an attractive
      approach to providing a surrogate cell source, not only for regenerative
      medicine, but also for pharmaceutical and toxicologic studies.

PMID- 21887387
TI  - Strategies of spinal fusion on osteoporotic spine.
AB  - The prevalence of osteoporosis has been increasing globally. Recently surgical
      indications for elderly patients with osteoporosis have been increasing. However,
      only few strategies are available for osteoporotic patients who need spinal
      fusion. Osteoporosis is a result of negative bone remodeling from enhanced
      function of the osteoclasts. Because bone formation is the result of coupling
      between osteoblasts and osteoclasts, anti-resorptive agents that induce
      osteoclast apoptosis may not be effective in spinal fusion surgery, necessitating
      new bone formation. Therefore, anabolic agents may be more suitable for
      osteoporotic patients who undergo spinal fusion surgery. The instrumentations and
      techniques with increased pullout strength may increase fusion rate through rigid
      fixation. Studies on new osteoinductive materials, methods to increase osteogenic
      cells, strengthened and biocompatible osteoconductive scaffolds are necessary to
      enable osteoporotic patients to undergo spinal fusion. When osteoporotic patients
      undergo spinal fusion, surgeons should consider appropriate osteoporosis
      medication, instrumentation and technique.

PMID- 21887388
TI  - Effect of amniotic membrane to reduce postlaminectomy epidural adhesion on a rat
      model.
AB  - OBJECTIVE: Epidural fibrosis and adhesion are the main reasons for post
      laminectomy sustained pain and functional disability. In this study, the authors
      investigate the effect of irradiated freeze-dried human amniotic membrane on
      reducing epidural adhesion after laminectomy on a rat model. METHODS: A total of
      20 rats were divided into two groups. The group A did not receive human amniotic
      membrane implantation after laminectomy and group B underwent human amniotic
      membrane implantation after laminectomy. Gross and microscopic findings were
      evaluated and compared at postoperative 1, 3 and 8 weeks. RESULTS: The amount of
      scar tissue and tenacity were reduced grossly in group of rats with human
      amniotic membrane implantation (group B). On a microscopic evaluation, there were
      less inflammatory cell infiltration and fibroblast proliferation in group B.
      CONCLUSION: This experimental study shows that implantation of irradiated freeze
      dried human amniotic membrane reduce epidural fibrosis and adhesion after spinal
      laminectomy in a rat model.

PMID- 21887389
TI  - Surgical results of unruptured intracranial aneurysms in the elderly : single
      center experience in the past ten years.
AB  - OBJECTIVE: As medical advances have increased life expectancy, it has become
      imperative to develop specific treatment strategies for intracranial aneurysms in
      the elderly. We therefore analyzed the clinical characteristics and outcomes of
      the treatment of unruptured intracranial aneurysms in patients older than 70
      years. METHODS: We retrospectively reviewed the medical records and results of
      neuroimaging modalities on 54 aneurysms of 48 consecutive patients with
      unruptured intracranial aneurysms. (mean+/-SD age, 72.11+/-1.96 years; range, 70
      78 years) who underwent surgical clipping over 10 years (May 1999 to June 2010).
      RESULTS: Of the 54 aneurysms, 22 were located in the internal carotid artery, 19
      in the middle cerebral artery, 12 in the anterior cerebral artery, and 1 in the
      superior cerebellar artery. Six patients had multiple aneurysms. Aneurysm size
      ranged from 3 mm to 17 mm (mean+/-SD, 6.82+/-3.07 mm). Fifty of the 54 aneurysms
      (92.6%) were completely clipped. Three-month outcomes were excellent in 50
      (92.6%) aneurysms and good and poor in 2 each (3.7%), with 1 death (2.0%).
      Procedure-related complications occurred in 7 aneurysms (13.0%), with 2 (3.7%)
      resulting in permanent neurological deficits, including death. No postoperative
      subarachnoid hemorrhage occurred during follow-up. The cumulative rates of stroke
      or death-free survival at 5 and 10 years were 100% and 78%, respectively.
      CONCLUSION: Surgical clipping of unruptured intracranial aneurysms in elderly
      group could get it as a favorable outcome in well selected cases.

PMID- 21887390
TI  - The clinical features of spinal leptomeningeal dissemination from malignant
      gliomas.
AB  - OBJECTIVE: The incidence of leptomeningeal dissemination from malignant glioma is
      rare, so the clinical features of this are not well documented yet. We attempted
      to determine the clinical features of leptomeningeal dissemination from malignant
      gliomas. METHODS: We retrospectively analyzed 11 cases of leptomeningeal
      dissemination of malignant glioma, who were treated at our institution between
      2006 and 2009. We investigated the clinical features of these patients by
      considering the following factors : tumor locations, the events of ventricular
      opening during surgery and the cerebrospinal fluid (CSF) profiles, including the
      cytology. RESULTS: The group was composed of 9 males and 2 females. The
      histological diagnosis of their initial intracranial tumors were 4 primary
      glioblastoma, 3 anaplastic astrocytoma, 1 anaplastic oligoastrocytoma, 2
      ganglioglioma and 1 pleomorphic xanthoastrocyotma with anaplastic features. The
      mean age of the patients at the time of the initial presentation was 42.8+/-10.3
      years. The mean time between surgery and the diagnosis of spinal dissemination
      was 12.3+/-7.9 (3-28) months. The mean overall survival after dissemination was
      2.7+/-1.3 months. All our patients revealed a history of surgical opening of the
      ventricles. Elevated protein in the CSF was reported for eight patients who had
      their CSF profiles checked. CONCLUSION: We propose that in the malignant gliomas,
      the surgical opening of ventricles can cause the spinal leptomeningeal
      dissemination and the elevated protein content of CSF may be a candidate marker
      of leptomeningeal dissemination.

PMID- 21887391
TI  - Visual outcome after transsphenoidal surgery in patients with pituitary apoplexy.
AB  - OBJECTIVE: Pituitary apoplexy is one of the most serious life-threatening
      complications of pituitary adenoma. The purpose of this study is to investigate
      the visual outcome after early transsphenoidal surgery for the patients with
      pituitary apoplexy. METHODS: We retrospectively reviewed the 31 patients with
      pituitary apoplexy who were admitted due to acute visual acuity or field
      impairment and treated by transsphenoidal surgery. Five patients were excluded
      because of the decreased conscious level. The visual acuity of each individual
      eye was evaluated by Snellen's chart. Visual fields were also checked using
      automated perimetry. To compare the visual outcome according to the surgical
      timing, we divided the patients into 2 groups. The first group, 21 of the
      patients have been undertaken transsphenoidal approach (TSA) within at least 48
      hours after admission. The second group included 8 patients who have been
      undertaken TSA beyond 48 hours. All patients were monitored at least 12 months
      after surgery. RESULTS: Patients were 21 males and 8 females (M : F=2.6 : 1) with
      the mean age of 42.4 years. Among the enrolled 29 patients, 26 patients presented
      with decreased visual acuity and 23 patients revealed the defective visual field
      respectively. Postoperatively, improvement in the visual acuity was seen in 15
      patients (83.3%) who underwent surgery within the first 48 hours of presentation,
      as compared to those in whom surgery was delayed beyond 48 hours (n=5; 62.5%)
      (p=0.014). Improvement in the visual field deficits was observed in 15 (88.2%) of
      patients who had been operated on within the first 48 hours of presentation, as
      compared to those in whom surgery was delayed beyond 48 hours (n=3; 50.0%)
      (p=0.037). CONCLUSION: This study suggests that rapid transsphenoidal surgery is
      effective to recover the visual impairment in patients with pituitary apoplexy.
      If there are associated abnormalities of visual acuity or visual fields in
      patients with hemorrhagic pituitary apoplexy, early neurosurgical intervention
      within 48 hours should be also required to recover visual impairment.

PMID- 21887392
TI  - Is All Anterior Oblique Fracture Orientation Really a Contraindication to
      Anterior Screw Fixation of Type II and Rostral Shallow Type III Odontoid
      Fractures?
AB  - OBJECTIVE: It is debatable whether an anterior oblique fracture orientation is
      really a contraindication to anterior odontoid screw fixation. The purpose of
      this study was to investigate the feasibility of anterior odontoid screw fixation
      of type II and rostral shallow type III fracture with an anterior oblique
      fracture orientation. METHODS: The authors evaluated 16 patients with type II and
      rostral shallow type III odontoid fracture with an anterior oblique fracture
      orientation. Of these 16 patients, 8 (group 1) were treated by anterior odontoid
      screw fixation, and 8 (group 2) by a posterior C1-2 arthrodesis. RESULTS: Of the
      8 patients in group 1, seven patients achieved solid bone fusion (87.5%), and one
      experienced screw back-out of the C-2 body two months after anterior screw
      fixation. All patients treated by posterior C1-C2 fusion in group 2 achieved
      successful bone fusion. Mean fracture displacements and fracture gaps were not
      significantly different in two groups. (p=0.075 and 0.782). However, mean
      fracture orientation angles were 15.3+/-3.2 degrees in group 1, and 28.6+8.1
      degrees in group 2 (p=0.002), and mean fragment angulations were 3.2+/-2.1
      degrees in group 1, and 14.8+/-6.7 degrees in group 2 (p=0.001). CONCLUSION: Even
      when the fracture lines of type II and rostral shallow type III fractures are
      oriented in an anterior oblique direction, anterior odontoid screw fixation can
      be feasible in carefully selected patients with a relatively small fracture
      orientation angle and relatively small fragment angulation.

PMID- 21887393
TI  - Targeting a safe entry point for c2 pedicle screw fixation in patients with
      atlantoaxial instability.
AB  - OBJECTIVE: This investigation was conducted to evaluate a new, safe entry point
      for the C2 pedicle screw, determined using the anatomical landmarks of the C2
      lateral mass, the lamina, and the isthmus of the pars interarticularis. METHODS:
      Fifteen patients underwent bilateral C1 lateral mass-C2 pedicle screw fixation,
      combined with posterior wiring. The C2 pedicle screw was inserted at the entry
      point determined using the following method : 4 mm lateral to and 4 mm inferior
      to the transitional point (from the superior end line of the lamina to the
      isthmus of the pars interarticularis). After a small hole was made with a high
      speed drill, the taper was inserted with a 30 degree convergence in the cephalad
      direction. Other surgical procedures were performed according to Harm's
      description. Preoperatively, careful evaluation was performed with a cervical X
      ray for C1-C2 alignment, magnetic resonance imaging for spinal cord and
      ligamentous structures, and a contrast-enhanced 3-dimensional computed tomogram
      (3-D CT) for bony anatomy and the course of the vertebral artery. A 3-D CT was
      checked postoperatively to evaluate screw placement. RESULTS: Bone fusion was
      achieved in all 15 patients (100%) without screw violation into the spinal canal,
      vertebral artery injury, or hardware failure. Occipital neuralgia developed in
      one patient, but this subsided after a C2 ganglion block. CONCLUSION: C2
      transpedicular screw fixation can be easily and safely performed using the entry
      point of the present study. However, careful preoperative radiographic
      evaluation, regardless of methods, is mandatory.

PMID- 21887394
TI  - Risk factors associated with subdural hygroma after decompressive craniectomy in
      patients with traumatic brain injury : a comparative study.
AB  - OBJECTIVE: Subdural hygroma (SDG) is a complication occurring after head trauma
      that may occur secondary to decompressive craniectomy (DC). However, the
      mechanism underlying SDG formation is not fully understood. Also, the
      relationship between the operative technique of DC or the decompressive effect
      and the occurrence and pathophysiology of SDG has not been clarified. Purpose of
      this study was to investigate the risk factors of SDG after DC in our series.
      METHODS: From January 2004 to December 2008, DC was performed in 85 patients who
      suffered from traumatic brain injury. We retrospectively reviewed the clinical
      and radiological features. For comparative analysis, we divided the patients into
      2 groups : one group with SDG after craniectomy (19 patients; 28.4% of the total
      sample), the other group without SDG (48 patients; 71.6%). The risk factors for
      developing SDG were then analyzed. RESULTS: The mean Glasgow Outcome Scale (GOS)
      scores at discharge of the groups with and without SDG were 2.8 and 3.1,
      respectively (p<0.0001). Analysis of radiological factors showed that a midline
      shift in excess of 5 mm on CT scans was present in 19 patients (100%) in the
      group with SDG and in 32 patients (66.7%) in the group without SDG (p<0.05). An
      accompanying subarachnoid hemorrhage (SAH) was seen in 17 patients (89.5%) in the
      group with SDG and in 29 patients (60.4%) in the group without SDG (p<0.05).
      Delayed hydrocephalus accompanied these findings in 10 patients (52.6%) in the
      group with SDG, versus 5 patients (10.4%) in the group without SDG (p<0.05). On
      CT, compression of basal cisterns was observed in 14 members (73.7%) in the group
      with SDG and in 18 members of the group without SDG (37.5%) (p<0.007).
      Furthermore, tearing of the arachnoid membrane, as observed on CT, was more
      common in all patients in the group with SDG (100%) than in the group without SDG
      (31 patients; 64.6%) (p<0.05). CONCLUSION: GOS showed statistically significant
      difference in the clinical risk factors for SDG between the group with SDG and
      the group without SDG. Analysis of radiological factors indicated that a midline
      shifting exceeding 5 mm, SAH, delayed hydrocephalus, compression of basal
      cisterns, and tearing of the arachnoid membrane were significantly more common in
      patients with SDG.

PMID- 21887395
TI  - Ewing's Sarcoma/Peripheral Primitive Neuroectodermal Tumor in the
      Cerebellopontine Angle : Diagnosis and Treatment.
AB  - Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) is an unusual
      malignancy with aggressive behavior. ES/PNET in the cerebellopontine angle (CPA)
      is extremely uncommon, and we report on a rare case here. A 31-year-old man
      presented with one month history of left facial palsy, hearing loss, swallowing
      difficulty, and hoarseness. Magnetic resonance images showed a large mass in the
      left CPA and a small one in the right cerebellar hemisphere. The patient
      underwent a surgery for the CPA mass lesion, and the pathology was compatible
      with ES/PNET. Radiation therapy and chemotherapy were administered. In contrast
      to the initial radiologic findings resembling vestibular schwannoma or
      meningioma, ES/PNET had several distinct clinical features. A patient with a CPA
      mass and presenting unusual clinical features should be suspected of having a
      rare malignancy.

PMID- 21887396
TI  - Cerebellar pilocytic astrocytomas with spontaneous intratumoral hemorrhage in
      adult.
AB  - Cerebellar pilocytic astrocytomas (PAs) are benign gliomas predominantly found in
      the pediatric population. Intracranial hemorrhages are extremely rare in initial
      presentations of cerebellar PAs. There are no reports in the medical literature
      of adult cerebellar PA cases presenting with intratumoral hemorrhage. We report 2
      cases of adult cerebellar pilocytic astrocytomas with intratumoral hemorrhage.
      The first case is a 37-year-old woman presenting with severe headache, nausea,
      and vomitting. Computed tomography demonstrated an acute hemorrhage adjacent to
      the right cerebellar hemisphere and hydrocephalus. Magnetic resonance imaging
      (MRI) revealed a cerebellar vermian tumor with the hemorrhage as a mixed
      isointense area in the T2-weighted image, and as a mixed hyperintense area in the
      contrast-enhanced T1-weighted image. The second case is a 53-year-old man
      presenting with headache for 3 weeks. MRI revealed a cerebellar hemispheric tumor
      with the hemorrhage as a mixed hyperintense area. It had a cystic mass with a
      heterogeneous enhanced mural nodule in the gadolinium-enhanced T1-weighted image
      and a fluid-fluid level within the cyst in the T2-weighted image. Both of them
      underwent radical resections of their respective lesions. Histological
      examination of the specimens revealed typical astrocytoma, including a
      hemorrhagic portion. Both patients recovered postoperatively and continue to do
      well at present. The medical literature on hemorrhagic cerebellar PAs is also
      reviewed.

PMID- 21887397
TI  - A case of angiocentric glioma with unusual clinical and radiological features.
AB  - Angiocentric glioma was recently recognized as a distinct clinicopathological
      entity in the 2007 World Health Organization classification of tumors of the
      central nervous system. Typically, it presents with seizure in children and young
      adults. However, our patient did not have a history of seizure. Seizure did not
      occur up to 6 months after operation. Although it usually does not have
      calcification brain magnetic resonance imaging in our patient showed T1
      hyperintense and T2-hypointense signals with calcification.

PMID- 21887398
TI  - Diagnostic usefulness of high resolution cross sectional MRI in symptomatic
      middle cerabral arterial dissection.
AB  - Dissection of the middle cerebral artery (MCA) is less frequent compared with
      dissection of the vertebrobasilar system or carotid artery. Recently, high
      resolution cross sectional MR imaging (HRMRI) has emerged as a potential
      technique for atherosclerotic plaque imaging in MCA. We introduce the findings of
      HRMRI in a 56-year-old woman with traumatic MCA dissection. HRMRI showed an
      intimal flap and tapered pseudolumen with intraluminal hemorrhage. We performed
      stent deployment about MCA dissection after failed medical treatment. Three
      months later, there was no in-stent restenosis and no further neurological
      deficit were noted.

PMID- 21887399
TI  - Angiographically occult vascular malformation of the cauda equina presenting
      massive spinal subdural and subarachnoid hematoma.
AB  - We report a case of a non traumatic spinal subdural hematoma or subarachnoid
      hematoma manifesting as lumbago, leg pain and bladder dysfunction that showed
      angiographically occult vascular malformation (AOVM). Although the spinal
      angiogram did not reveal any vascular abnormality, the follow-up magnetic
      resonance image showed AOVM. Complete surgical removal was performed due to the
      aggravated bladder dysfunction. This case highlights the need to consider
      bleeding due to spinal AOVM, even when angiography is negative.

PMID- 21887401
TI  - Intraosseous hemangioblastoma mimicking spinal metastasis in the patient with
      renal cell carcinoma.
AB  - Sporadic osseous hemangioblastomas in the vertebra are extremely rare and they
      can be misdiagnosed as a vertebral hemangioma or metastasis in imaging studies.
      We report an intraosseous hemangioblastoma that arose from the 11th thoracic
      vertebra and was diagnosed initially as a metastasis in a patient with renal cell
      carcinoma. Diagnosis, surgical treatment and adjuvant radiosurgery of such case
      in reference to the literature are discussed.

PMID- 21887400
TI  - Spinal intradural extramedullary cavernoma presenting with intracranial
      superficial hemosiderosis.
AB  - A case of intradural extramedullary cavernous angioma is presented with headache,
      dizziness, and bilateral sensorineural hearing loss caused by an intracranial
      superficial hemosiderosis. It was incidentally found in a patient with a 3-month
      history of sustained headache, dizziness and a 3-year history of hearing
      difficulty. The neurological examination was unremarkable in the lower extremity.
      MR images showed an intracranial superficial hemosiderosis mostly in the
      cerebellar region. Myelography and MR images of the thoracolumbar spine revealed
      an intradural extramedullary mass, which was pathologically proven to be a
      cavernous angioma. T12 total laminoplastic laminotomy and total tumor removal
      were performed without any neurologic deficits. The patient's symptoms, including
      headache and dizziness, have been absent for three years. Intradural
      extramedullary cavernous angioma can present with an intracranial superficial
      hemosiderosis as a result of chronic subarachnoid hemorrhage.

PMID- 21887402
TI  - Sudden foot drop caused by foraminal gas pseudocyst.
AB  - A foraminal gas pseudocyst is a rare cause of lumbar radiculopathy. The
      association with a sudden foot drop has not been previously reported. Here, a 67
      year-old woman with sudden foot drop on the left side is reported. Computed
      tomography and magnetic resonance imaging identified a foraminal gas containing
      lesion compressing the left L5 root at the L5-S1 foramen. The foraminal gas
      containing lesion compressing the L5 ganglion was successfully removed by the
      posterior approach. The histological diagnosis was a gas pseudocyst. This unique
      case of surgically proven gas pseudocyst indicates that it should be included in
      the differential diagnosis of patients presenting with sudden foot drop.

PMID- 21887404
TI  - Nativity Differentials in Older Age Mortality in Taiwan: Do They Exist and Why?
AB  - Comparisons of migrants versus native populations have become increasingly
      important as a means of gaining insight into the factors affecting health and
      mortality levels and the relationship between them. Taiwan underwent a unique
      migration in 1949-50, as more than a million people, mostly young men, arrived
      from Mainland China following the Communist civil war victory. The Mainlanders
      were distinct from the original settlers in several ways: they represented
      different provinces in China, were better educated, and had distinct occupational
      profiles. Since 1950, Taiwan has experienced a rapid demographic transition and
      notable economic development, resulting in mortality decline. In this paper, we
      generate age- and cause-specific death rates circa 1990 by education and nativity
      to evaluate the relative importance of each factor. We also use longitudinal
      survey data to help interpret the differentials in terms of selection, risk
      factors, and other dynamics of health and mortality.

PMID- 21887403
TI  - Structure-activity relationship of conformationally constrained peptidomimetics
      for antiproliferative activity in HER2-overexpressing breast cancer cell lines.
AB  - Human epidermal growth factor receptor 2 (HER2) is a member of the human
      epidermal growth factor receptor kinases and is involved in a signaling cascade
      for cell growth and differentiation. It is well established that HER2-mediated
      heterodimerization has important implications in cancer. Deregulation of
      signaling pathways and overexpression of HER2 is known to occur in cancer cells,
      indicating the role of HER2 in tumorigenesis. Therefore, blocking HER2-mediated
      signaling has potential therapeutic value. We have designed several
      peptidomimetics to inhibit HER2-mediated signaling for cell growth. One of the
      compounds (compound 5, Arg-[3-amino-3(1-napthyl)-propionic acid]-Phe) exhibited
      antiproliferative activity with IC(50) values in the nanomolar to micromolar
      range in breast cancer cell lines. To further investigate the structure-activity
      relationship of the compounds, various analogs of compound 5 were designed.
      Conformational constraints were initiated in the peptidomimetic with introduction
      of a Pro residue in the peptidomimetic sequence. Results of antiproliferative
      activity indicated that analogs of compound 5 with C-and N-terminal ends capped
      (compound 16) and compound 9 with Asp at the C-terminal exhibited
      antiproliferative activity in the lower micromolar range against breast cancer
      cell lines. Introduction of conformational constraints such as Pro residue in the
      sequence or cyclization did not enhance the activity of the peptidomimetic.
      Competitive binding studies were carried out to evaluate the binding of potent
      peptidomimetics to HER2-overexpressing cancer cell lines. Results indicated that
      compounds exhibiting antiproliferative activity in breast cancer cell lines bind
      to the cells that overexpress HER2 protein.

PMID- 21887405
TI  - Localizing single molecules in three dimensions - a brief review.
AB  - Single molecule tracking in three dimensions (3D) in a live cell environment
      holds the promise of revealing important new biological insights. However,
      conventional microscopy based imaging techniques are not well suited for fast 3D
      tracking of single molecules in cells. Previously we developed an imaging
      modality multifocal plane microscopy (MUM) to image fast intracellular dynamics
      in 3D in live cells. Recently, we have reported an algorithm, the MUM
      localization algorithm (MUMLA), for the 3D localization of point sources that are
      imaged using MUM. Here, we present a review of our results on MUM and MUMLA. We
      have validated MUMLA through simulated and experimental data and have shown that
      the 3D-position of quantum dots (QDs) can be determined with high spatial
      accuracy over a wide spatial range. We have calculated the Cramer-Rao lower bound
      for the problem of determining the 3D location of point sources from MUM and from
      conventional microscopes. Our analyses shows that MUM overcomes the poor depth
      discrimination of the conventional microscope, and thereby paves the way for high
      accuracy tracking of nanoparticles in a live cell environment. We have also shown
      that the performance of MUMLA comes consistently close to the Cramer-Rao lower
      bound.

PMID- 21887406
TI  - Growth factor/growth factor receptor loops in autocrine growth regulation of
      human prostate cancer DU145 cells.
AB  - Autocrine growth factors produced by epithelial cells mediate the development and
      proliferation of neoplastic human prostate tissue. Various approaches have been
      used to down-regulate neoplastic growth of prostate cancer using natural
      flavonoids, soluble receptors, pseudo-ligands, monoclonal antibodies and tyrosine
      kinase inhibitors (tyrphostins). Selected growth factor/growth factor receptor
      loops (mainly TGFalpha/EGFR and IGFs/IGFIR) have been proposed as regulators of
      prostate cancer cell growth. We have previously determined that blockade of IGFIR
      or VEGF2R signaling pathways by tyrphostin AG1024 and SU1498 inhibits autocrine
      growth and viability of DU145 cells in vitro. Recently, we compared the activity
      of AG1024 and SU1498 with the inhibiting effect of tyrphostin A23 (a selective
      inhibitor of EGFR). The results described in this paper confirm that DU145 cells
      do not produce IGFI or EGF. In contrast, DU145 cells produce a great amount of
      VEGF, much more than TGFalpha (about 60-fold), and VEGF may be the real autocrine
      growth factor of the investigated cells. The results indicate that the growth of
      DU145 may be regulated by at least three autocrine loops: TGFalpha/EGFR,
      IGFII/IGFIR and VEGF/VEGFR2. Neither AG1024 nor SU1498 affected the production of
      TGFalpha substantially, which excludes the possibility that IGFRs or VEGFR2
      inhibitors arrest the growth of these cells by inhibition of synthesis and/or
      secretion of TGFalpha. The obtained data indicate that all tree investigated
      tyrphostins (AG1024, SU1498 and A23) inhibit signal transmission by Akt (PKB),
      ERK(1/2), Src and STAT in a similar manner. A comparison of the effects of the
      investigated tyrphostins indicates that TGFalpha, IGFII and VEGF stimulate cell
      growth by affecting the same signaling pathway. The hypothesis was confirmed by
      the effect of the investigated tyrphostins on activation of EGFR. All these
      inhibitors decreased phosphorylation of EGFR to the same extent, and after the
      same time of incubation with cell culture. These results strongly suggest that
      stimulation of EGFR kinase is the main step in the initiation of mitogen
      signaling in DU145 cells, regardless of the type of ligand (TGFalpha, IGFs or
      VEGF) and their specific receptors.

PMID- 21887407
TI  - Inulin supplementation in rat model of pouchitis.
AB  - Available data indicates potential effectiveness of prebiotic therapy in
      alleviating inflammation and prolonging the remission in inflammatory bowel
      disease. Documented successes of such therapies were the basis for this study. So
      far, there is no data related to the effectiveness of inulin application in
      symptomatic or severe pouchitis in humans or in animal model. The aim of the
      study was to determine the effect of inulin supplementation on the expression of
      intestinal inflammation and feeding efficiency in rats with induced pouchitis.
      Twenty-four Wistar rats were operated. After induction of pouchitis animals were
      randomly divided into control and supplementation groups receiving, respectively,
      semi-synthetic diet with or without inulin (in a lower (LD) or higher (HD) dose:
      2.5 % or 5 % of total dietary content of mass) for a period of 6 weeks. Selected
      nutritional parameters were assessed throughout the study. Histopathological and
      immunohistochemical analysis of pouch mucosa specimens was also performed. The
      energy intake, weight gain, feeding efficiency, quality of stools were comparable
      in all studied groups. The intensity of inflammation (Moskovitz scale) and
      adaptive changes (Laumonier scale) did not differ between compared groups. The
      tissue expression of pro- and anti-inflammatory interleukins (IL-1alpha, IL-6, IL
      10 and IL-12)  was not different either. Inulin supplementation does not improve
      the quality of stools or the expression of intestinal inflammation in rats with
      induced pouchitis. It has no impact on the intensity of pouch adaptation or on
      feeding efficiency.

PMID- 21887408
TI  - Human hAtg2A protein expressed in yeast is recruited to preautophagosomal
      structure but does not complement autophagy defects of atg2Delta strain.
AB  - Yeast Atg2, an autophagy-related protein, is highly conserved in other fungi and
      has two homologues in humans, one of which is hAtg2A encoded by the
      hATG2A/KIAA0404 gene. Region of homology between Atg2 and hAtg2A proteins
      comprises the C-terminal domain. We used yeast atg2D strain to express the GFP
      KIAA0404 gene, its fragment or fusions with yeast ATG2, and study their effects
      on autophagy. The GFP-hAtg2A protein localized to punctate structures, some of
      which colocalized with Ape1-RFP-marked preautophagosomal structure (PAS), but it
      did not restore autophagy in atg2Delta cells. N-terminal fragment of Atg2 and N
      terminal fragment of hAtg2A were sufficient for PAS recruitment but were not
      sufficient to function in autophagy. Neither a fusion of the N-terminal fragment
      of hAtg2A with C-terminal domain of Atg2 nor a reciprocal fusion were functional
      in autophagy. hAtg2A, in contrast to yeast Atg2, did not show interaction with
      the yeast autophagy protein Atg9 but both Atg2 proteins showed interaction with
      Atg18, a phospholipid-binding protein, in two-hybrid system. Moreover, deletion
      of ATG18 abrogated PAS recruitment of hAtg2A. Our results show that human hAtg2A
      can not function in autophagy in yeast, however, it is recruited to the PAS,
      possibly due to the interaction with Atg18.

PMID- 21887409
TI  - Hepatoprotective effect of aqueous extract of Aframomum melegueta on ethanol
      induced toxicity in rats.
AB  - In recent years there have been remarkable developments in the prevention of
      diseases, especially with regards to the role of free radicals and antioxidants. 
      Ethanol-induced oxidative stress appears to be one mechanism by which ethanol
      causes liver injury. The protective effect of aqueous plant extract of Aframomum
      melegueta on ethanol-induced toxicity was investigated in male Wistar rats. The
      rats were treated with 45 % ethanol (4.8 g/kg b.w.t.) for 16 days to induce
      alcoholic diseases in the liver. The activities of alanine aminotransferase,
      aspartate aminotransferase and triglyceride were monitored and the histological
      changes in liver examined in order to evaluate the protective effects of the
      plant extract. Hepatic malondialdehyde and reduced glutathione, as well as
      superoxide dismutase and glutathione-S-transferase activities were determined for
      the antioxidant status. Chronic ethanol administration resulted in a
      statistically significant elevation of serum alanine aminotransferases and
      triglyceride levels, as well as a decrease in reduced glutathione and superoxide
      dismutase which was dramatically attenuated by the co-administration of the plant
      extract.  Histological changes were related to these indices. Co-administration
      of the plant extract suppressed the elevation of lipid peroxidation, restored the
      reduced glutathion, and enhanced the superoxide dismutase activity. These results
      highlight the ability of Aframomum melegueta to ameliorate oxidative damage in
      the liver and the observed effects are associated with its antioxidant
      activities.

PMID- 21887410
TI  - Conventional calpains and programmed cell death.
AB  - The evidence on the crucial role of a family of calcium-dependent cysteine
      proteases called calpains in programmed cell death is rich and still growing.
      However, understanding of the mechanisms of their functions in apoptosis is not
      full yet. Calpains have been implicated in both physiological and pathological
      cell death control, especially in various malignancies, but also in the immune
      system development and function. There is also growing evidence on calpain
      involvement in apoptosis execution in certain pathological conditions of the
      central nervous system, in cardiovascular diseases, etc. Understanding of the
      clinical significance of calpain activation pathways, after intense studies of
      the influence of calpain activity on drug-induced apoptosis, seems especially
      important lately, as calpains have become noticed as potential therapeutic
      targets. To allow pharmacological targeting of these enzymes, thorough knowledge
      of their patterns of activation and further interactions with already known
      apoptotic pathways is necessary. A comprehensive summary of both well established
      and recently obtained information in the field is an important step that may lead
      to future advances in the use of calpain-targeted agents in the clinic.

PMID- 21887411
TI  - Kinetic cooperativity of tyrosinase. A general mechanism.
AB  - Tyrosinase shows kinetic cooperativity in its action on o-diphenols, but not when
      it acts on monophenols, confirming that the slow step is the hydroxylation of
      monophenols to o-diphenols. This model can be generalised to a wide range of
      substrates; for example, type S(A) substrates, which give rise to a stable
      product as the o-quinone evolves by means of a first or pseudo first order
      reaction (alpha-methyl dopa, dopa methyl ester, dopamine, 3,4
      dihydroxyphenylpropionic acid, 3,4-dihydroxyphenylacetic acid, alpha-methyl
      tyrosine, tyrosine methyl ester, tyramine, 4-hydroxyphenylpropionic acid and 4
      hydroxyphenylacetic acid), type S(B) substrates, which include those whose o
      quinone evolves with no clear stoichiometry (catechol, 4-methylcatechol, phenol
      and p-cresol) and, lastly, type S(C) substrates, which give rise to stable o
      quinones (4-tert-butylcatechol/4-tert-butylphenol).

PMID- 21887412
TI  - Conformational destabilization of Bacillus licheniformis alpha-amylase induced by
      lysine modification and calcium depletion.
AB  - Bacillus licheniformis alpha-amylase (BLA) was chemically modified using 100-fold
      molar excess of succinic anhydride over protein or 0.66 M potassium cyanate to
      obtain 42 % succinylated and 81 % carbamylated BLAs. Size and charge homogeneity
      of modified preparations was established by Sephacryl S-200 HR gel chromatography
      and polyacrylamide gel electrophoresis. Conformational alteration in these
      preparations was evident by the larger Stokes radii (3.40 nm for carbamylated and
      3.34 nm for succinylated BLAs) compared to 2.43 nm obtained for native BLA. Urea
      denaturation results using mean residue ellipticity (MRE) as a probe also showed
      conformational destabilization based on the early start of transition as well as
      DeltaG(D)(H(2)O) values obtained for both modified derivatives and Ca-depleted
      BLA. Decrease in DeltaG(D)(H(2)O) value from 5,930 cal/mol (for native BLA) to
      3,957 cal/mol (for succinylated BLA), 3,336 cal/mol (for carbamylated BLA) and
      3,430 cal/mol for Ca-depleted BLA suggested reduced conformational stability upon
      modification of amino groups of BLA or depletion of calcium. Since both
      succinylation and carbamylation reactions abolish the positive charge on amino
      groups (both alpha- and epsilon- amino), the decrease in conformational stability
      can be ascribed to the disruption of salt bridges present in the protein which
      might have released the intrinsic calcium from its binding site.

PMID- 21887413
TI  - Cardiac endothelial cells isolated from mouse heart - a novel model for
      radiobiology.
AB  - Cardiovascular disease is recognized as an important clinical problem in
      radiotherapy and radiation protection. However, only few radiobiological models
      relevant for assessment of cardiotoxic effects of ionizing radiation are
      available. Here we describe the isolation of mouse primary cardiac endothelial
      cells, a possible target for cardiotoxic effects of radiation. Cells isolated
      from hearts of juvenile mice were cultured and irradiated in vitro. In addition,
      cells isolated from hearts of locally irradiated adult animals (up to 6 days
      after irradiation) were tested. A dose-dependent formation of histone gammaH2A.X
      foci was observed after in vitro irradiation of cultured cells. However, such
      cells were resistant to radiation-induced apoptosis. Increased levels of actin
      stress fibres were observed in the cytoplasm of cardiac endothelial cells
      irradiated in vitro or isolated from irradiated animals. A high dose of 16 Gy did
      not increase permeability to Dextran in monolayers formed by endothelial cells.
      Up-regulated expression of Vcam1, Sele and Hsp70i genes was detected after
      irradiation in vitro and in cells isolated few days after irradiation in vivo.
      The increased level of actin stress fibres and enhanced expression of stress
      response genes in irradiated endothelial cells are potentially involved in
      cardiotoxic effects of ionizing radiation.

PMID- 21887414
TI  - Fenoterol did not enhance glucocorticoid-induced skeletal changes in male rats.
AB  - Glucocorticoids and beta(2)-adrenergic receptor agonists are the most commonly
      used drugs in the treatment of asthma. Both therapies are potentially dangerous
      to the skeletal system. The aim of the present study was to investigate the
      effects of fenoterol, a beta(2)-receptor agonist, on the development of bone
      changes induced by glucocorticoid (prednisolone) administration in mature male
      rats. The experiments were carried out on 24-week-old male Wistar rats. The
      effects of prednisolone 21-hemisuccinate sodium salt (7 mg/kg s.c. daily) or/and
      fenoterol hydrobromide (1.4 mg/kg i.p. daily), administered for 4 weeks, on the
      skeletal system were studied. Bone turnover markers, geometric parameters, mass,
      mass of bone mineral in the tibia, femur and L-4 vertebra, bone histomorphometric
      parameters and mechanical properties of tibial metaphysis, femoral diaphysis and
      femoral neck were determined. Both prednisolone and fenoterol had damaging
      effects on the skeletal system of mature male rats. However, concurrent
      administration of fenoterol and prednisolone did not result in the
      intensification of the deleterious skeletal effect of either drug administered
      separately.

PMID- 21887416
TI  - Multi-molecule reaction of serum albumin can occur through thiol-yne coupling.
AB  - The free-radical hydrothiolation of alkynes (thiol-yne coupling, TYC) unites two
      thiol fragments across the carbon-carbon triple bond to give a dithioether
      derivative with exclusive 1,2-addition; this reaction can be used for
      modification of peptides and proteins allowing glycoconjugation and fluorescent
      labeling. These results have implications not only as a flexible strategy for
      attaching two modifications at a single site in proteins but also for
      unanticipated side-reactions of reagents (such as cycloalkynes) used in other
      protein coupling reactions.

PMID- 21887417
TI  - Electronic structure in real time: mapping valence electron rearrangements during
      chemical reactions.
AB  - The interest in following the evolution of the valence electronic structure of
      atoms and molecules during chemical reactions on a femtosecond time scale is
      discussed. By explicitly mapping the occupied part of the electronic structure
      with femtosecond pump-probe schemes one essentially follows the electrons making
      the bonds while the bonds change. This holds the key to unprecedented insight
      into chemical bonding in short-lived intermediates and reveals the coupled motion
      of electrons and nuclei. Examples from the recent literature on small molecules
      and anionic clusters in the gas phase and on atoms and molecules on surfaces
      using lab-based femtosecond laser methods are used to demonstrate the case. They
      highlight how the evolution of the valence electronic structure can be probed
      with time-resolved photoelectron spectroscopy with ultraviolet (UV) probe photon
      energies of up to 6 eV. It is shown how new insight can be gained by extending
      the probing wavelength into the vacuum-ultraviolet (VUV) region to photon
      energies of 20 eV and more by accessing the whole occupied valence electronic
      structure with time-resolved VUV photoelectron spectroscopy. Finally, the
      importance of soft X-ray free-electron lasers with probe photon energies of
      several hundred eV and femtosecond pulses and in particular the key role of
      femtosecond time-resolved soft X-ray emission spectroscopy or resonant inelastic
      X-ray scattering for mapping the electronic structure during chemical reactions
      is discussed.

PMID- 21887418
TI  - Studying the interaction of carbohydrate-protein on the dendrimer-modified solid
      support by microarray-based plasmon resonance light scattering assay.
AB  - Here, a three-dimensional (3D) carbohydrate microarray-based plasmon resonance
      light scattering (RLS) assay has been established for studying carbohydrate
      lectin binding with high selectivity. The 3D carbohydrate microarray is
      fabricated by immobilizing amino-modified carbohydrates on the home-made fourth
      generation (G4) NH(2)-terminated poly(amidoamine) dendrimers (PAMAM)-modified
      substrate. After marking the carbohydrate-lectin binding events by 13 nm peptide
      stabilized gold nanoparticles through the biotin-avidin reaction, the 3D
      microarray can be directly detected by the RLS scanner without the conventional
      silver enhancement step. The well defined recognition systems: three
      monosaccharides (Man-alpha, Glc-alpha and Gal-beta) with two lectins (Con A and
      RCA 120), have been chosen here to establish the RLS assay, respectively.
      Quantitative determination of the surface dissociation constants (K(D,surf)) for
      surface carbohydrates and lectins has been achieved. In addition, inhibition
      values (i.e. the inhibition constants (K(i)) and the concentrations of inhibitors
      required to produce 50% inhibition (IC(50))) for inhibitors in solution are also
      demonstrated by the saccharide competing assays.

PMID- 21887419
TI  - Synthesis and dissipative particle dynamics simulation of cross-linkable
      fluorinated diblock copolymers: self-assembly aggregation behavior in different
      solvents.
AB  - Developing microstructures, such as low molecular aggregates, spherical micelles
      and multi-compartment micelles, is an expanding area of research in Materials
      Science. By applying an atom transfer radical polymerization (ATRP) process to
      cross-linkable fluorinated diblock copolymers and analyzing the data we are able
      to demonstrate the potential for developing films with different micro-structures
      for additional biological research. Applying the Dissipative Particle Dynamic
      (DPD) Method, Transmission Electron Microscopy (TEM) and Scanning Electron
      Microscopy (SEM) techniques to cross-linkable fluorinated diblock copolymers of
      (methyl methacrylate-co-hydroxyethyl methacrylate-co-butyl methacrylate)-b-2
      (perfluoroalkyl)ethyl methacrylate (MMA-co-HEMA-co-BMA-b-FMA) we were able to
      analyze the structures and their relationships to the aggregation of various
      microstructure formations through the use of various solvents in the process. For
      the self-assembly of the cross-linkable diblock copolymer in solutions, the DPD
      simulation results are only in qualitative agreement with experimental data of
      aggregate morphologies and sizes. This suggests an improved approach to creating
      materials and methods necessary for studying microstructures in films used in
      other research areas. Our work examines whether using selective solvents can be
      easily extended to prepare aggregates with different morphologies, which is an
      effective shortcut to obtain films with different microstructures. DPD simulation
      can be considered as an adjunct to experiments and provides other valuable
      information for the experiment.

PMID- 21887420
TI  - An ultrasensitive electrochemical sensor for the mercuric ion via controlled
      assembly of SWCNTs.
AB  - An ultrasensitive "turn-on" electrochemical sensor for the Hg(2+) ion was
      proposed based on the T-Hg(2+)-T coordination chemistry and the controlled
      assembly of SWCNTs on the MHA/SAM-modified gold electrode.

PMID- 21887421
TI  - Bioconjugation of CdSe/ZnS nanoparticles with SNAP tagged proteins.
AB  - A method for protein immobilization onto modified CdSe/ZnS quantum dot surfaces
      was developed using simple SNAP tag methodology.

PMID- 21887422
TI  - Photoreversible cellular imaging using photochrome-conjugated fullerene silica
      nanoparticles.
AB  - Photochromic compound-conjugated fluorescent fullerene-silica nanoparticles
      prepared by the reverse-microemulsion method was utilized for photoswitchable
      cellular imaging by repeatable irradiation of ultraviolet and visible light.

PMID- 21887423
TI  - Free energy calculations for a flexible water model.
AB  - In this work, we consider the problem of calculating the classical free energies
      of liquids and solids for molecular models with intramolecular flexibility. We
      show that thermodynamic integration from the fully-interacting solid of interest
      to a Debye crystal reference state, with anisotropic harmonic interactions
      derived from the Hessian of the original crystal, provides a straightforward
      route to calculating the Gibbs free energy of the solid. To calculate the
      molecular liquid free energy, it is essential to correctly account for
      contributions from both intermolecular and intramolecular motion; we employ
      thermodynamic integration to a Lennard-Jones reference fluid, coupled with direct
      evaluation of the molecular ro-vibrational partition function. These approaches
      are used to study the low-pressure classical phase diagram of the flexible q
      TIP4P/F water model. We find that, while the experimental ice-I/liquid and ice
      III/liquid coexistence lines are described reasonably well by this model, the ice
      II phase is predicted to be metastable. In light of this finding, we go on to
      examine how the coupling between intramolecular flexibility and intermolecular
      interactions influences the computed phase diagram by comparing our results with
      those of the underlying rigid-body water model.

PMID- 21887424
TI  - Investigating the CO2 uncaging mechanism of nitrophenylacetates by means of fs-IR
      spectroscopy and quantum chemical calculations.
AB  - Caged compounds are widely utilized for light-triggered control of biological and
      chemical reactions. In our study we investigated the photo-induced
      decarboxylation of all three constitutional isomers of nitrophenylacetate (NPA),
      which can be regarded as caged-CO(2). UV-pump/IR-probe spectroscopy was used to
      directly observe the nascent CO(2) in the region of 2340 cm(-1). Together with
      quantum chemical calculations the reaction models for all three components could
      be obtained. For meta- and para-NPA the main decarboxylation pathway proceeds via
      a triplet state with a lifetime of 0.2 ns. In the case of ortho-NPA the
      photodecarboxylation reaction is suppressed by an H(+)- or H-transfer reaction in
      the excited state as a result of the proximity of the nitro and acetate
      substituents. Nevertheless, the photodecarboxylation can be investigated due to
      the isolated spectral position of the CO(2) band. The analysis of the data
      reveals that a weak ultrafast release channel (<300 fs) represents the main
      photodecarboxylation reaction pathway for ortho-NPA. The detailed understanding
      of the molecular mechanisms of CO(2) uncaging should provide general guidelines
      for the design of systematically improved nitrobenzyl cages.

PMID- 21887425
TI  - Bioactive glasses as potential radioisotope vectors for in situ cancer therapy:
      investigating the structural effects of yttrium.
AB  - The incorporation of yttrium in bioactive glasses (BGs) could lead to a new
      generation of radionuclide vectors for cancer therapy, with high
      biocompatibility, controlled biodegradability and the ability to enhance the
      growth of new healthy tissues after the treatment with radionuclides. It is
      essential to assess whether and to what extent yttrium incorporation affects the
      favourable properties of the BG matrix: ideally, one would like to combine the
      high surface reactivity typical of BGs with a slow release of radioactive
      yttrium. Molecular Dynamics simulations show that, compared to a BG composition
      with the same silica fraction, incorporation of yttrium results in two opposing
      effects on the glass durability: a more fragmented silicate network (leading to
      lower durability) and a stronger yttrium-mediated association between separate
      silicate fragments (leading to higher durability). The simulations also highlight
      a high site-selectivity and some clustering of yttrium cations, which are likely
      linked to the observed slow rate of yttrium released from related Y-BG
      compositions. Optimisation of yttrium BG compositions for radiotherapy
      applications thus depends on the delicate balance between these effects.

PMID- 21887426
TI  - Polar solvation dynamics in water and methanol: search for molecularity.
AB  - Time-dependent Stokes shifts (TDSS) were measured for diverse polarity probes in
      water, heavy water, methanol, and benzonitrile, by broadband fluorescence up
      conversion with 85 fs time resolution. In water the spectral dynamics is solute
      independent and quantitatively described by simple dielectric continuum theory of
      solvation. In methanol the slower part of the TDSS is solute-dependent. A
      correlation with anisotropy decay suggests that methanol solvation dynamics is
      modulated by orientational solute diffusion. An empirical power law which links
      the solvation relaxation function of a mobile solute to that of an immobile
      solute is experimentally verified. Activation energies for the average relaxation
      rate are also given. Solvation dynamics in H(2)O and D(2)O are identical at and
      above 20  degrees C but diverge below.

PMID- 21887427
TI  - Graphene and carbon nanotube composite electrodes for supercapacitors with ultra
      high energy density.
AB  - We describe a graphene and single-walled carbon nanotube (SWCNT) composite film
      prepared by a blending process for use as electrodes in high energy density
      supercapacitors. Specific capacitances of 290.6 F g(-1) and 201.0 F g(-1) have
      been obtained for a single electrode in aqueous and organic electrolytes,
      respectively, using a more practical two-electrode testing system. In the organic
      electrolyte the energy density reached 62.8 Wh kg(-1) and the power density
      reached 58.5 kW kg(-1). The addition of single-walled carbon nanotubes raised the
      energy density by 23% and power density by 31% more than the graphene electrodes.
      The graphene/CNT electrodes exhibited an ultra-high energy density of 155.6 Wh
      kg(-1) in ionic liquid at room temperature. In addition, the specific capacitance
      increased by 29% after 1000 cycles in ionic liquid, indicating their excellent
      cyclicity. The SWCNTs acted as a conductive additive, spacer, and binder in the
      graphene/CNT supercapacitors. This work suggests that our graphene/CNT
      supercapacitors can be comparable to NiMH batteries in performance and are
      promising for applications in hybrid vehicles and electric vehicles.

PMID- 21887428
TI  - Switching the photoinduced processes in host-guest complexes of beta-cyclodextrin
      substituted silicon(IV) phthalocyanines and a tetrasulfonated porphyrin.
AB  - Porphyrins and phthalocyanines are two attractive classes of functional dyes for
      the construction of artificial light harvesting and charge separation molecular
      systems. The assembly of these components by supramolecular approach is of
      particular interest as this provides a facile route to build multi-chromophoric
      arrays with various architectures and tuneable photophysical properties. We
      report herein a series of host-guest complexes formed between a tetrasulfonated
      porphyrin and several silicon(IV) phthalocyanines substituted axially with two
      permethylated beta-cyclodextrin units via different spacers. As shown by
      electronic absorption and fluorescence spectroscopic methods, the two components
      bind spontaneously in a 1:1 manner in water with large binding constants in the
      range of 1.1 * 10(7) to 3.5 * 10(8) M(-1). The photophysical properties of the
      resulting supramolecular complexes have also been studied in detail using steady
      state and time-resolved optical spectroscopic methods. It has been found that two
      major photoinduced processes, namely fluorescence resonance energy transfer and
      charge transfer are involved which are controlled by the spacer between the beta
      cyclodextrin units and the silicon centre of phthalocyanine. Despite the fact
      that charge transfer is a thermodynamically favourable process for all the
      complexes, only the ones with a tetraethylene glycol or oxo linker exhibit an
      efficient charge transfer from the excited phthalocyanine to the porphyrin
      entity. The lifetimes of the corresponding charge-separated states have been
      determined to be 200 and 70 ps by picosecond pump-probe experiments.

PMID- 21887429
TI  - Visible luminescence spectroscopy of free-base and zinc phthalocyanines isolated
      in cryogenic matrices.
AB  - The absorption, emission and excitation spectra of ZnPc and H(2)Pc trapped in Ne,
      N(2), Ar, Kr and Xe matrices have been recorded in the region of the Q states. A
      comparison of the matrix fluorescence spectra with Raman spectra recorded in KBr
      pellets reveals very strong similarities. This is entirely consistent with the
      selection rules and points to the occurrence of only fundamental vibrational
      transitions in the emission spectra. Based on this behaviour, the vibronic modes
      in emission have been assigned using results obtained recently on the ground
      state with large basis-set DFT calculations [Murray et al. PCCP, 12, 10406
      (2010)]. Furthermore, the very strong mirror symmetry between excitation and
      emission has allowed these assignments to be extended to the excitation
      (absorption) bands. While this approach works well for ZnPc, coupling between the
      band origin of the S(2)(Q(Y)) state and vibrationally excited levels of
      S(1)(Q(X)), limits the range of its application in H(2)Pc. The Q(X)/Q(Y) state
      coupling is analysed from data obtained from site-selective excitation spectra,
      revealing pronounced matrix and site effects. From this analysis, the splitting
      of the Q(X) and Q(Y) states has been determined more accurately than in any
      previous attempts.

PMID- 21887430
TI  - Ultrafast transient mid IR to visible spectroscopy of fully reduced flavins.
AB  - The light sensing apparatus of many organisms includes a flavoprotein. In any
      spectroscopic analysis of the photocycle of flavoproteins a detailed knowledge of
      the spectroscopy and excited state dynamics of potential intermediates is
      required. Here we correlate transient vibrational and electronic spectra of the
      two fully reduced forms of flavin adenine dinucleotide (FAD): FADH(-) and
      FADH(2). Ground and excited state frequencies of the characteristic carbonyl
      modes are observed and assigned with the aid of DFT calculations. Excited state
      decay and ground state recovery dynamics of the two states are reported. Excited
      state decay occurs on the picosecond timescale, in agreement with the low
      fluorescence yield, and is markedly non single exponential in FADH(-). Further,
      an unusual 'inverse' isotope effect is observed in the decay time of FADH(-),
      suggesting the involvement in the radiationless relaxation coordinate of an NH or
      hydrogen bond mode that strengthens in the excited electronic state. Ground state
      recovery also occurs on the picosecond time scale, consistent with radiationless
      decay by internal conversion, but is slower than the excited state decay.

PMID- 21887431
TI  - Electrogenerated chemiluminescence of triazole-modified deoxycytidine analogues
      in N,N-dimethylformamide.
AB  - Triazole-modified deoxycytidines have been prepared for incorporation into single
      stranded deoxyribonucleic acid (ssDNA). Electrochemical responses and
      electrogenerated chemiluminescence (ECL) of these deoxycytidine (dC) analogues, 1
      4, were investigated as the monomers. Cyclic voltammetry and differential pulse
      voltammetry techniques were used to determine the oxidation and reduction
      potentials of 1-4, along with the reversibility of their electrochemical
      reactions. The dC analogues, in N,N-dimethylformamide containing 0.1 M tetra-n
      butylammonium perchlorate as electrolyte, exhibited weak relative ECL
      efficiencies following the annihilation mechanism, while these efficiencies were
      enhanced with the use of benzoyl peroxide following the coreactant mechanism. It
      was shown that these nucleosides could generate excited monomers, and excimers as
      seen by the red-shifted ECL maxima relative to their corresponding
      photoluminescence peak wavelengths.

PMID- 21887432
TI  - A multifaceted approach to hydrogen storage.
AB  - The widespread adoption of hydrogen as an energy carrier could bring significant
      benefits, but only if a number of currently intractable problems can be overcome.
      Not the least of these is the problem of storage, particularly when aimed at use
      onboard light-vehicles. The aim of this overview is to look in depth at a number
      of areas linked by the recently concluded HYDROGEN research network, representing
      an intentionally multi-faceted selection with the goal of advancing the field on
      a number of fronts simultaneously. For the general reader we provide a concise
      outline of the main approaches to storing hydrogen before moving on to detailed
      reviews of recent research in the solid chemical storage of hydrogen, and so
      provide an entry point for the interested reader on these diverse topics. The
      subjects covered include: the mechanisms of Ti catalysis in alanates; the
      kinetics of the borohydrides and the resulting limitations; novel transition
      metal catalysts for use with complex hydrides; less common borohydrides; protic
      hydridic stores; metal ammines and novel approaches to nano-confined metal
      hydrides.

PMID- 21887433
TI  - Large ultra-high molecular weight polyethylene spherical particles produced by
      AlR3 activated half-sandwich chromium(III) catalysts.
AB  - A series of half-sandwich pentamethylcyclopentadienyl chromium(III) complexes
      bearing a salicylaldiminato ligand, Cp*[2-R(1)-4-R(2)-6-(CH==NR(3))C(6)H(2)O]CrCl
      [R(1) = (i)Pr (1, 4), (t)Bu (2, 3, 5), Ad (6); R(2) = H (1, 2, 3), (t)Bu (4, 5,
      6); R(3) = (i)Pr (1, 2, 5, 6), (t)Bu (3, 4)], were synthesized. All complexes
      were characterized by elemental analyses and the structures of complexes 1-4 and
      6 were determined by X-ray diffraction analysis. These complexes adopt a pseudo
      octahedral coordination environment with a three-legged piano stool geometry.
      Upon activation with a small amount of AlR(3), complexes 1-6 all catalyze the
      polymerization of ethylene in a quasi living fashion with good to high catalytic
      activity under mild conditions and produce ultra-high molecular weight
      polyethylene as spherical particles with a diameter of 1-6 mm. The catalytic
      activity of these complexes and the molecular weight of the produced polyethylene
      can be tuned in a broad range by changing the R(1), R(2), and R(3) groups as well
      as the AlR(3) cocatalyst. It was found that complex 6 with R(1) = Ad, R(2) =
      (t)Bu, and R(3) = (i)Pr shows the highest catalytic activity and produces
      polyethylene with the highest molecular weight.

PMID- 21887434
TI  - The application of novel hydrophobic ionic liquids to the extraction of
      uranium(VI) from nitric acid medium and a determination of the uranyl complexes
      formed.
AB  - Novel ammonium based hydrophobic ionic liquids (ILs) have been synthesised and
      characterised, and their use in the liquid-liquid extraction of uranium(VI) from
      an aqueous nitric acid solution using tri-n-butyl phosphate (TBP), studied. On
      varying the nitric acid concentration, each IL was found to give markedly
      different results. Relatively hydrophilic ILs showed high uranium(VI)
      extractability at 0.01 M nitric acid solution which progressively decreased from
      0.01 to 2 M HNO(3) and then increased again as the nitric acid concentration was
      increased to 6 M. An analysis of the mechanisms involved for one such IL, pointed
      to cationic-exchange being the predominant route at low nitric acid
      concentrations whilst at high nitric acid concentrations, anionic-exchange
      predominated. Strongly hydrophobic ILs showed low extractability for nitric acid
      concentrations below 0.1 M but increasing extractability from 0.1 M to 6 M nitric
      acid. The predominant mechanism in this case involved the partitioning of a
      neutral uranyl complex. The uranyl complexes were found to be UO(2)(2+).(TBP)(3)
      for the cationic exchange mechanism, UO(2)(NO(3))(2)(TBP)(2) for the neutral
      mechanism and UO(2)(NO(3))(3)(-).(TBP) for the anionic exchange mechanism.

PMID- 21887435
TI  - Syntheses, structures and properties of silver-organic frameworks constructed
      with 1,2,3,4-benzenetetracarboxylic acid.
AB  - The reactions of 1,2,3,4-benzenetetracarboxylic acid (H(4)mpda) and different
      silver(I) salts under hydrothermal or solvent evaporation conditions yielded four
      unusual coordination complexes with interesting frameworks: [Ag(4)(mpda)](n) (1),
      {[Ag(2.5)(mpda)(bpy)(2)].[Ag(bpy)].[Ag(bpy)(H(2)O)].(NO(3))(0.5).(H(2)O)(9)}(n)
      (2),
      {[Ag(5)(mpda)(2)(bpy)(4)].[Ag(bpy)].[Ag(bpy)(H(2)O)].[Ag(bpy)(H(2)O)].(H(2)O)(16)
      (n) (3), {[Ag(2)(mpda)(H(2)O)].[Ag(bpy)].[Ag(bpy)]}(n) (4) (bpy = 4,4'
      bipyridine). Complex 1 displays a novel (3,4,7)-connected
      {4.6(2)}{4.6(5)}{4(2).6(13).8(5).10} topology, in which the carboxylic groups of
      the mpda(4-) ligand adopt variable coordination modes. In 1, besides Ag-O
      coordination bonding, AgAg and Agaromatic intermolecular interactions also make
      their appearance. In complexes 2-4, rare architectures comprising three or four
      isolated coordination polymers within the same crystalline structure have been
      obtained, respectively. In 2 and 3, neighboring layers are linked together
      through water tapes into a three-dimensional supramolecular architecture, which
      is also consolidated by pi...pi stacking, while independent infinite rod-like
      polymer chains fill the void space between layers. Interestingly, an anionic
      (H(2)O-NO(3)(-))(n) layer, built from water tapes and nitrate anions as well as
      consolidated by the mpda(4-) ligands, has been structurally identified in
      compound 2. A new water tape constructed from alternating tetramers and decamers
      has been obtained in compound 3. In compound 4, a right-handed helical chain and
      two rod-like polymeric chains are interconnected through host-guest molecular
      recognition to generate a three-dimensional chiral supramolecular architecture.
      Bulk materials for 1 and 4 have second-harmonic generation activity, being
      approximately 0.6 and 0.4 times that of urea. The IR spectra, thermogravimetric
      analysis and luminescent properties of all compounds were also investigated.

PMID- 21887436
TI  - Co(II), Mn(II) and Cu(II)-directed coordination polymers with mixed tetrazolate
      dicarboxylate heterobridges exhibiting spin-canted, spin-frustrated
      antiferromagnetism and a slight spin-flop transition.
AB  - Three new paramagnetic ion-directed coordination frameworks,
      {[Co(4)(H(2)O)(2)(MU(3)-OH)(2)(atz)(2)(nip)(2)].3H(2)O}(n) (1),
      {[Mn(4)(H(2)O)(2)(MU(3)-OH)(2)(atz)(2)(nip)(2)].H(2)O.MeOH}(n) (2) and
      {[Cu(2)(H(2)O)(MU(3)-OH)(atz)(nip)].2H(2)O}(n) (3), were, respectively, obtained
      by solvo-/hydrothermal reactions of 5-amino-1H-tetrazole (Hatz), 5
      nitroisophathalic acid (H(2)nip) with an inorganic Co(II), Mn(II) or Cu(II) salt.
      The former two complexes are two-dimensional (2D) covalent layers built from
      butterfly-shaped tetranuclear M(4)(MU(3)-OH)(2) clusters and double atz(-) and
      nip(2-) linkers. Whereas complex 3 is a 3D framework with scarcely observed
      corner-sharing Cu(3)(MU(3)-OH) Delta-chains extended by nip(2-) linkages, in
      which the anionic atz(-) ligand acts as a reinforcement to consolidate the Delta
      chain. Magnetically, due to the interplay of the anisotropy of spin carrier and
      magnetic exchange interactions from the adjacent spin carriers, the complexes
      exhibit spin-canted antiferromagnetism with a Neel temperature lower than 2.0 K
      for 1 and an antiferromagnetic ordering with a slight field-induced spin-flop
      transition for 2. In contrast, complex 3 with a local Kagome sublattice displays
      spin-frustrated antiferromagnetic behavior with magnetic ordering at 16.0 K.

PMID- 21887437
TI  - Synthesis and structure of cationic guanidinate-bridged bimetallic {Li7M} cubes
      (M = Mn, Co, Zn) with inverse crown counter anions.
AB  - The reactions of the heteroleptic lithium amide [Li(3)(MU-hmds)(2)(MU,MU-hpp)]
      (1), where [hmds](-) = hexamethyldisilazide and [hpp](-) =
      hexahydropyrimidopyrimidide, with MnCl(2), CoCl(2) or ZnBr(2) result in the
      formation of the separated ion-pairs [MLi(7)(MU(8)-O)(MU,MU-hpp)(6)](+)[A](-),
      which each consist of a {MLi(7)} oxo-centred cube structural motif (M = Mn 2, Co
      4, Zn 5), with each face of the cube being bridged by an [hpp](-) ligand. In the
      case of M = Mn and Co, the counter ion, [A](-), is the pentagonal anionic inverse
      crown [{Li(MU-hmds)}(5)(MU(5)-Cl)](-) (3), whereas the reaction with M = Zn
      produces the known tris-amido zincate [Zn(hmds)(3)](-) counter anion.

PMID- 21887438
TI  - Controlled loading of cryoprotectants (CPAs) to oocyte with linear and complex
      CPA profiles on a microfluidic platform.
AB  - Oocyte cryopreservation has become an essential tool in the treatment of
      infertility by preserving oocytes for women undergoing chemotherapy. However,
      despite recent advances, pregnancy rates from all cryopreserved oocytes remain
      low. The inevitable use of the cryoprotectants (CPAs) during preservation affects
      the viability of the preserved oocytes and pregnancy rates either through CPA
      toxicity or osmotic injury. Current protocols attempt to reduce CPA toxicity by
      minimizing CPA concentrations, or by minimizing the volume changes via the step
      wise addition of CPAs to the cells. Although the step-wise addition decreases
      osmotic shock to oocytes, it unfortunately increases toxic injuries due to the
      long exposure times to CPAs. To address limitations of current protocols and to
      rationally design protocols that minimize the exposure to CPAs, we developed a
      microfluidic device for the quantitative measurements of oocyte volume during
      various CPA loading protocols. We spatially secured a single oocyte on the
      microfluidic device, created precisely controlled continuous CPA profiles (step
      wise, linear and complex) for the addition of CPAs to the oocyte and measured the
      oocyte volumetric response to each profile. With both linear and complex
      profiles, we were able to load 1.5 M propanediol to oocytes in less than 15 min
      and with a volumetric change of less than 10%. Thus, we believe this single
      oocyte analysis technology will eventually help future advances in assisted
      reproductive technologies and fertility preservation.

PMID- 21887439
TI  - Synthesis of mono- and di-[12]aneN3 ligands and study on the catalytic cleavage
      of RNA model 2-hydroxypropyl-p-nitrophenyl phosphate with their metal complexes.
AB  - A series of mono- and di-[12]aneN(3) ligands 1-6, which contain different
      substituents on the coordinating backbone, different linkers between two
      [12]aneN(3) units and different N-methylation on the [12]aneN(3) units, have been
      synthesized and fully characterized. The catalytic activities of their metal
      complexes on the cleavage of RNA model phosphate 2-hydroxypropyl-p-nitrophenyl
      phosphate (HPNPP) varied with the structures of the ligands and metal ions. Click
      reactions afforded an efficient method to prepare a series of [12]aneN(3)
      ligands, however, the incorporation of triazole moieties reduced the catalytic
      activities due to their coordination with metal ions and the strong inhibition
      from the triflate counter ion. Dinuclear zinc(II) complexes containing an m-xylyl
      bridge showed higher catalytic activities with synergistic effects up to 700
      fold. Copper(II) complexes with the ligands without triazole moieties proved to
      be highly reactive and showed strong cooperativity between the two copper(II)
      ions. In terms of k(2), dinuclear complexes Zn(2)-3b, Zn(2)-3d, Zn(2)-4b, and
      Cu(2)-4b afforded activities of 7.9 * 10(5), 3.9 * 10(4), 9.0 * 10(4), and 8.1 *
      10(4)-fold higher than that of methoxide. The ortho arrangement of the two
      [12]aneN(3) units and the presence of 5- or 2-positioned substituents in the
      benzene ring as well as N-methylation of [12]aneN(3) units greatly reduced the
      catalytic activities due to the steric effects. These results clearly indicate
      that the structures of the linker between two [12]aneN(3) units play very
      important role in their catalytic synergistic effects.

PMID- 21887441
TI  - The future of metal-organic frameworks.
AB  - A personal perspective recognising the developments in the field of metal-organic
      frameworks, of where the challenges currently lie and the opportunities that are
      on the horizon.

PMID- 21887440
TI  - Mn2+ complexes of 1-oxa-4,7-diazacyclononane based ligands with acetic,
      phosphonic and phosphinic acid pendant arms: stability and relaxation studies.
AB  - A new class of macrocyclic ligands based on 1-oxa-4,7-diazacyclononane was
      synthesized and their Mn(2+) complexes were investigated with respect to
      stability and relaxation properties. Each ligand has two pendant arms involving
      carboxylic (H(2)L(1)--1-oxa-4,7-diazacyclononane-4,7-diacetic acid), phosphonic
      (H(4)L(2)--1-oxa-4,7-diazacyclononane-4,7-bis(methylenephosphonic acid)),
      phosphinic (H(2)L(3)--1-oxa-4,7-diazacyclononane-4,7-bis(methylenephosphinic
      acid)) or phenylphosphinic (H(2)L(4)--1-oxa-4,7-diazacyclononane-4,7
      bis[methylene(phenyl)phosphinic acid]) acid moieties. H(2)L(3) and H(2)L(4) were
      synthesized for the first time. The crystal structure of the Mn(2+) complex with
      H(2)L(4) confirmed a coordination number of 6 for Mn(2+). The protonation
      constants of all ligands and the stability constants of their complexes with
      Mn(2+) and some biologically or biomedically relevant metal ions were determined
      by potentiometry. The protonation sequence of H(2)L(3) was followed by (1)H and
      (31)P NMR titration and the second protonation step was attributed to the second
      macrocyclic nitrogen atom. The potentiometric data revealed a relatively low
      thermodynamic stability of the Mn(2+) complexes with all ligands investigated.
      For H(2)L(3) and H(2)L(4), full Mn(2+) complexation cannot be achieved even with
      100% ligand excess. The transmetallation of MnL(1) and MnL(2) with Zn(2+) was too
      fast to be followed at pH 6. Variable temperature (1)H NMRD and (17)O NMR
      measurements have been performed on MnL(1) and MnL(2) to provide information on
      water exchange and rotational dynamics. The (17)O chemical shifts indicate
      hydration equilibrium between mono- and bishydrated species for MnL(1), while
      MnL(2) is monohydrated. The water exchange is considerably faster on MnL(1)
      (k(ex)(298) = 1.2 * 10(9) s(-1)) than on MnL(2) (k(ex)(298) = 1.2 * 10(7) s(-1)).
      Small endogenous anions (phosphate, carbonate, citrate) do not replace the
      coordinated water in either of the complexes, but they induce their slow
      decomposition. All Mn(2+) complexes are stable toward air-oxidation.

PMID- 21887442
TI  - Divergent Pd(II) and Au(III) mediated nitroalkynol cycloisomerizations.
AB  - A new cycloisomerization reaction comprising the simultaneous addition of nitro
      and alcohol groups across C=C leading to skeletally diverse small molecules is
      documented.

PMID- 21887443
TI  - Spectroscopic properties and upconversion in Pr3+:YF3 nanoparticles.
AB  - The synthesis and spectroscopic investigation of Pr(3+):YF(3) nanoparticles with
      nominal concentration between 0.05% and 5 at% Pr(3+) are reported. Pr(3+)
      emission in the visible range of the spectrum is investigated at room temperature
      and at 10 K as well as time resolved spectroscopy as a function of Pr(3+)
      concentration. The upconverted emission from the orange to the blue region is
      observed and the time-resolved spectroscopy of the visible emissions is discussed
      as a function of the doping level. A careful analysis of the decays permits
      identification of the main energy-transfer mechanisms that determine the
      population of the excited levels at various times during the decay.

PMID- 21887444
TI  - Nanomorphology-driven two-stage hole mobility in blend films of regioregular and
      regiorandom polythiophenes.
AB  - We report the nanomorphology-driven two-stage hole mobility in the blend films of
      regioregular and regiorandom poly(3-hexylthiophene) (P3HT) polymers of which
      regioregularity was 92.2% and 33.0%, respectively. The hole mobility of blend
      films was measured by employing a top-contact type organic field-effect
      transistor which has an aromatic polyimide gate insulating layer and silver
      source/drain electrodes. Results showed that the hole mobility of blend films was
      suddenly reduced as large as two orders of magnitude as the bulk regioregularity
      of blend films decreased from 89.8% to 86.3%, even though the hole mobility
      change was far less than one order of magnitude after and before this boundary
      condition. The discontinuous two-stage hole mobility trend has been attributed to
      the destruction of P3HT chain ordering/alignment in the blend films at the
      boundary blend composition, as evidenced from the huge changes in optical
      absorption coefficient, surface nanomorphology, and in-plane/out-of-plane
      nanostructures in the blend films.

PMID- 21887445
TI  - (R)-(+)-N-methylbenzoguanidine ((R)-NMBG) catalyzed kinetic resolution of racemic
      secondary benzylic alcohols with free carboxylic acids by asymmetric
      esterification.
AB  - (R)-(+)-N-Methylbenzoguanidine ((R)-NMBG) was found to function as an efficient
      acyl-transfer catalyst for the kinetic resolution of racemic secondary benzylic
      alcohols in the presence of achiral carboxylic acids and pivalic anhydride. The
      use of a tertiary amine in this reaction is not necessary to attain good chemical
      yields of the products. It was determined that diphenylacetic acid could be
      employed as the most suitable acyl donor for achieving a high enantioselectivity
      for the kinetic resolution of the racemic secondary benzylic alcohols having
      normal aliphatic alkyl chains at the C-1 positions. On the other hand, a less
      hindered carboxylic acid, such as 3-phenylpropanoic acid, functioned as a better
      acyl donor for the kinetic resolution of racemic secondary benzylic alcohols
      having branched aliphatic alkyl chains at the C-1 positions.

PMID- 21887446
TI  - Nitric oxide-releasing ruthenium nanoparticles.
AB  - Nitric oxide-releasing ruthenium nanoparticles were synthesized by the reaction
      of alkanethiolate-protected ruthenium nanoparticles with tert-butyl nitrite
      ((t)BuONO), and their water-soluble derivatives are able to deliver NO to
      proteins such as reduced myoglobin upon light irradiation in aqueous media.

PMID- 21887451
TI  - The photobiology of melanocytes modulates the impact of UVA on sunlight-induced
      melanoma.
AB  - Ultraviolet radiation is responsible for melanoma. In this review, we address the
      role of the different UV spectra in melanoma. The data suggest that only UVB is
      capable of initiating melanoma, and that both UVA and UVB are involved in the
      progression of the disease. The etiology of sunlight-induced melanoma may be
      different for chronically-exposed tumors and for those located on body surfaces
      with considerably less exposure. Solar signature mutations are most likely
      associated with the progression of chronically-exposed tumors. The unique
      relationship between UVA and melanocytes, and the role of melanin in
      photocarcinogenesis is discussed. The current state of knowledge strongly
      indicates that UVA, regardless of its source, is involved in melanoma and should
      be avoided to deter progression of incipient tumors.

PMID- 21887452
TI  - Mechanistic studies on two dinuclear organogold(III) compounds showing
      appreciable antiproliferative properties and a high redox stability.
AB  - Two dinuclear oxo-bridged organogold(III) compounds, namely [(N,N,C)(2)Au(2)(MU
      O)][PF(6)](2) (with N,N,CH = 6-(1-methylbenzyl)-2,2'-bipyridine, Au(2)O1; or 6
      (1,1-dimethylbenzyl)-2,2'-bipyridine, Au(2)O2), were previously prepared and
      characterised. Their solution chemistry under physiological-like conditions has
      been investigated here as well as their in vitro antiproliferative properties.
      Notably, these compounds reveal a marked redox stability even in the presence of
      effective biological reductants such as ascorbic acid and glutathione. The two
      dinuclear gold(iii) compounds were evaluated for cytotoxic actions against a
      representative panel of 12 human tumor cell lines, in comparison to respective
      mononuclear parent compounds [(N,N,C)AuOH][PF(6)], and appreciable biological
      activity could be highlighted. The reactions of Au(2)O1 and Au(2)O2 with a few
      model proteins were studied and the ability to form metallodrug-protein adducts
      monitored through ESI MS methods. Typical adducts were identified where the
      protein is associated to monometallic gold fragments; in these adducts gold
      remains in the oxidation state +3 and conserves its organic ligand. A direct
      comparison of the biological profiles of these binuclear organogold(III)
      compounds with those previously reported for a series of dinuclear oxo-bridged
      complexes [(N,N)(2)Au(2)(MU-O)(2)][PF(6)](2) (N,N = 6(6')-substituted 2,2'
      bipyridines) named Auoxo's was carried out. It emerges that the greater
      cytotoxicity of the latter is mainly due to the greater oxidising power of their
      gold(III) centres and to propensity to generate gold(i) species; in contrast, the
      here described bimetallic organogold(III) complexes manifest a far higher redox
      stability in the biological milieu coupled to lower, but still significant,
      antiproliferative properties. Different molecular mechanisms are thus
      hypothesised for these two classes of dinuclear gold(III) agents.

PMID- 21887453
TI  - Click-chemistry approach to isoxazole-containing alpha-CF3-substituted alpha
      aminocarboxylates and alpha-aminophosphonates.
AB  - A convenient strategy for the synthesis of isoxazole-containing alpha-CF(3)
      substituted alpha-aminocarboxylates and alpha-aminophosphonates have been
      developed. The method is based on copper-catalyzed 1,3-dipolar cycloaddition of
      different aromatic nitrile oxides to functionalized acetylenes.

PMID- 21887454
TI  - Lymphocyte function following radioiodine therapy in patients with thyroid
      carcinoma.
AB  - AIM: Since the nuclear disaster in Fukushima has raised great concern about the
      danger of radioactivity, we here addressed the question if the therapeutic use of
      iodine 131, the most frequently applied radionuclide, was harmful to immune
      function in patients. It was our aim to define for the first time in a clinical
      setting how radioiodine therapy alters anti-microbial immune responses. PATIENTS,
      METHODS: In 21 patients with thyroid carcinoma anti-microbial lymphocyte
      responses were assessed by lymphocyte transformation test and ELISpot - measuring
      lymphocyte proliferation and on a single cell level production of pro- and anti
      inflammatory cytokines (interferon-gamma and interleukin-10) - prior to therapy,
      at day 1 and day 7 post therapy. RESULTS: Proliferative lymphocyte responses and
      interferon-gamma production after in vitro stimulation with microbial antigens
      were significantly (p < 0.05) increased at day 1 vs. pre therapy, and returned to
      pre therapy levels at day 7. On the contrary, at day 1 interleukin-10 production
      was significantly (p < 0.05) reduced. Thus, we observed a short-term increase in
      pro-inflammatory immune responses. However, T lymphocyte responses were in the
      range of healthy controls at all three time points. CONCLUSION: Thyroid carcinoma
      patients receiving radioiodine therapy do not display any sign of
      immunosuppression.

PMID- 21887455
TI  - Evaluation of a filter-prepared platelet concentrate for the treatment of
      suspensory branch injuries in horses.
AB  - OBJECTIVES: Platelet preparations have become a treatment for soft tissue
      injuries in horses. This study evaluated a novel filter-based system to
      concentrate platelets and assesses its value in the treatment of suspensory
      ligament branch desmitis. METHODS: Filtered platelet concentrate was prepared
      from 55 ml of venous blood obtained from 21 normal horses. Platelets and white
      blood cells in whole blood and filtered platelet concentrate were measured, as
      was platelet activating factor (PAF)-induced platelet-derived growth factor-BB
      (PDGF-BB) release. Eleven horses with 18 focal acute suspensory ligament branch
      injuries were treated intra-lesionally with autologous filtered platelet
      concentrate and evaluated clinically and ultrasonographically for one to three
      years. RESULTS: The increase in concentration of platelets in the filtered
      concentrate in comparison with whole blood (6.9 +/- 1.9-fold) was significantly
      greater than the increase in white blood cells (3.8 +/- 0.8-fold) (p <0.0001).
      There was no effect of sex or breed on platelet concentration. Platelets were
      responsive to PAF with >100-fold higher levels of PDGF release over basal levels.
      All hypoechoic lesions re-evaluated within three months had resolved. Five of the
      11 horses returned to their previous level of work, one was exercising at a lower
      level, three were retired, one died for unrelated reasons, and one was still
      convalescing. CLINICAL SIGNIFICANCE: Filtered platelet concentrate was easily and
      reliably prepared and injected into suspensory ligament branch injuries without
      short-term complications. This treatment was associated with rapid resolution of
      ultrasonographic lesions and lameness. Filtered platelet concentrate represents a
      convenient alternative for the treatment of suspensory ligament branch injuries.

PMID- 21887456
TI  - Honokiol stimulates osteoblastogenesis by suppressing NF-kappaB activation.
AB  - Magnolia officinalis, a component of Asian herbal teas, has long been employed in
      traditional Japanese and Chinese medicine to treat numerous maladies. Honokiol, a
      biphenolic compound, is now considered to be one of the major active ingredients
      of Magnolia extract, and is under intense investigation for its anti-angiogenic,
      anti-inflammatory, anti-tumor and neuroprotective properties. Biochemically,
      honokiol has been recognized to modulate the nuclear factor kappa B (NF-kappaB)
      signal transduction pathway suggesting that it possesses anti-inflammatory
      properties. Inflammation is intimately associated with bone turnover and skeletal
      deterioration and consequently, anti-inflammatory drugs may hold significant
      promise as bone protective agents to stem bone loss in osteoporotic conditions.
      We and others have demonstrated that suppression of NF-kappaB blunts osteoclastic
      bone resorption, but promotes osteoblastic bone formation. Indeed previous
      studies have demonstrated the anti-osteoclastogenic effects of honokiol, however,
      activities on osteoblast differentiation and activity have yet to be
      investigated. In this study, we show that honokiol is a potent inducer of in
      vitro osteoblast differentiation by virtue of its capacity to suppress basal and
      tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation and to
      alleviate the suppressive action of TNFalpha on bone morphogenetic protein (BMP)
      2-induced Smad activation. Our data confirm that honokiol may have considerable
      promise as a dual anabolic/anti-catabolic agent for the amelioration of multiple
      osteoporotic diseases.

PMID- 21887457
TI  - Evaluation of CMV and KAP promoters for driving the expression of human CYP4F2 in
      transgenic mice.
AB  - A transgenic mouse model in which cytochrome P450 4F2 (CYP4F2) was expressed in
      multiple organs was expected to clarify the role of 20-hydroxyeicosatetraenoic
      acid (20-HETE) in the regulation of blood pressure, compared with our previously
      established kidney androgen-regulated protein (KAP) promoter CYP4F2 transgenic
      mouse model which predominantly showed renal overexpression of CYP4F2. A novel
      CYP4F2 transgenic mouse model driven by the cyto-megalovirus (CMV) promoter was
      generated and identified by PCR and subsequent sequencing. Extensive study of CMV
      CYP4F2 transgenic mice demonstrated that CYP4F2 was exclusively expressed in the
      liver, while 20-HETE levels in the urine, kidney and blood were not affected, and
      there was no resulting change in the systolic blood pressure. This was in
      contrast to KAP-CYP4F2 transgenic mice which exerted prohypertensive action of 20
      HETE resulting from the renal overexpression of CYP4F2. In addition, CYP4F2
      overwhelmed the endogenous renal Cyp4a family mRNA levels in the KAP-CYP4F2 but
      not in the CMV-CYP4F2 transgenic mice. These results support the idea that
      overexpression of renal CYP4F2, leading to high 20-HETE in the urine and blood,
      may account for the elevated blood pressure. The CMV promoter did not direct
      CYP4F2 expression into extensive tissues and organs in an attempt to clarify the
      action of 20-HETE.

PMID- 21887458
TI  - Suppression of proliferation and oxidative stress by extracts of Ganoderma
      lucidum in the ovarian cancer cell line OVCAR-3.
AB  - Lingzhi (LZ) is a medical mushroom also known as Ganoderma lucidum, which has
      been used in traditional Chinese medicine for more than 4,000 years and moreover,
      due to its presumed health benefits and apparent absence of side-effects it has
      also been widely consumed as a dietary supplement by cancer patients and by
      individuals diagnosed with various chronic diseases. The reported benefits of
      Ganoderma lucidum may be largely ascribed to its biologically active constituent
      polysaccharides and triterpenes known as ganoderic acids having structural
      similarity to steroid hormones. Laboratory studies have shown that Ganoderma
      lucidum enhances immune functions and also inhibits growth of various cancer
      cells both in vitro and in vivo. However, the mechanism by which Ganoderma
      lucidum exerts its chemopreventive activities remains unknown. In this study, we
      investigated whether Ganoderma lucidum elicits its anti-tumor effects by
      suppressing cell growth and inducing antioxidative/detoxification activity in
      human ovarian OVCAR-3 cells. The results showed that Ganoderma lucidum inhibits
      cell growth and disruption of cell cycle progression via down regulation of
      cyclin D1. Chemopreventive activities elicited by Ganoderma lucidum were
      demonstrated by the induction of antioxidant SOD and catalase as well as the
      phase II detoxification enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1) and
      glutathione S-transferase P1 (GSTP1) via the Nrf2 mediated signaling pathway
      known to provide chemoprotection against carcinogenicity. These findings indicate
      that Ganoderma lucidum possesses chemopreventive potential contributing to its
      overall health effects and further suggest that Ganoderma lucidum may have
      clinical applications as an adjunct supplementary agent in chemotherapy.

PMID- 21887459
TI  - The metabolic syndrome of fructose-fed rats: effects of long-chain
      polyunsaturated omega3 and omega6 fatty acids. II. Time course of changes in food
      intake, body weight, plasma glucose and insulin concentrations and insulin
      resistance.
AB  - The time course for changes in food intake, body weight, plasma glucose and
      insulin concentrations and HOMA index was monitored over a period of 8 weeks in
      rats exposed from the 8th week after birth to diets containing either starch or
      fructose and sunflower oil. In two further groups of rats exposed to the fructose
      rich diet part of the sunflower oil was substituted by either salmon oil rich in
      long-chain polyunsaturated omega3 fatty acids or safflower oil rich in long-chain
      polyunsaturated omega6 fatty acids. Despite lower food intake, the gain in body
      weight was higher in fructose-fed rats than in starch-fed rats. The
      supplementation of the fructose-rich diet by either omega3 or omega6 fatty acids
      lowered both food intake and body weight gain. The measurements of plasma glucose
      and insulin concentrations, HOMA index and insulinogenic index performed after
      overnight starvation were in fair agreement with those recorded at the occasion
      of an intraperitoneal glucose tolerance test, with higher values for plasma
      glucose concentration and HOMA index in the fructose-fed rats exposed to the
      sunflower oil (with or without enrichment with omega6 fatty acids) than in the
      starch-fed rats exposed to the sunflower oil or fructose-fed rats exposed to a
      diet enriched with omega3 fatty acids. Such was also the case for the
      measurements of glycated albumin at sacrifice. Moreover, the insulinogenic index
      was lower in the fructose-fed rats with or without dietary enrichment in omega6
      fatty acids than in the fructose-fed rats with dietary enrichment in omega3 fatty
      acids. The elucidation of the biochemical determinants of the later difference
      requires further investigations in isolated pancreatic islets.

PMID- 21887460
TI  - Trastuzumab enhances the anti-tumor effects of the histone deacetylase inhibitor
      sodium butyrate on a HER2-overexpressing breast cancer cell line.
AB  - Trastuzumab has efficacy to improve the effect of cytotoxic drugs, such as
      paclitaxel and anthracyclin, against HER2-overexpressing breast cancer cells.
      Sodium butyrate (NaB), a histone deacetylase inhibitor, is known to have
      antitumoral properties. However, whether and how trastuzumab possesses the
      potential to synergize the anti-tumor effect of NaB on breast cancer cells is
      still equivocal. To elucidate whether combined treatment with NaB and trastuzumab
      exerts anti-tumor effects on a HER2-overexpressing breast cancer cell line, SKBR3
      cells were treated with NaB alone or in combination with trastuzumab, and the
      effects on proliferation and cell cycle progression were analyzed. Combinatory
      treatment with NaB (4 mmol/l) and trastuzumab (20 ug/ml) significantly increased
      the growth-inhibitory effect on SKBR3 breast cancer cells, in comparison to NaB
      or trastuzumab treatment alone. The growth-inhibitory effect of the combination
      of NaB and trastuzumab was accompanied by elevated mRNA and protein levels of the
      cyclin-dependent kinase inhibitor p27Kip1. In contrast, this effect was absent in
      HER2-negative HCC1937 cells. In conclusion, trastuzumab significantly improved
      the antitumor effect of NaB on HER2-overexpressing breast cancer cell line in
      vitro.

PMID- 21887461
TI  - Increased P-glycoprotein expression in mitochondria is related to acquired
      multidrug resistance in human hepatoma cells depleted of mitochondrial DNA.
AB  - Mitochondrial DNA-depleted rho0 cells are resistant to apoptosis, but the
      mechanism remains unclear. A human hepatoma cell line (SK-Hep1) depleted of mtDNA
      (rho0SK-Hep1) was induced by ethidium bromide treatment. The rho0SK-Hep1 cells
      were resistant to both doxorubicin- and cisplatin-induced apoptosis, while
      cybrids (SK-Hep1Cyb) prepared by fusing rho0SK-Hep1 cells with platelets showed
      restored susceptibility to both drugs. We observed P-glycoprotein and MRP1 were
      both overexpressed in rho0 cells, and more P-glycoproteins were localized in the
      mitochondria and were functionally active. rho0 cells showed resistance to
      chemotherapeutic drug-induced apoptosis. The increased expression and
      localization of P-glycoproteins in the mitochondria of rho0 cells may facilitate
      the exclusion of chemotherapeutic drugs from the mitochondria to the cytosol.

PMID- 21887462
TI  - Bufotalin sensitizes death receptor-induced apoptosis via Bid- and STAT1
      dependent pathways.
AB  - Tumor necrosis factor-alpha (TNF-alpha) and TNF-related apoptosis-inducing ligand
      (TRAIL) are apoptosis-inducing ligands that stimulate death receptors. In this
      study, we investigated the effects of bufotalin, a major compound in toad venom,
      on sensitizing TNF-alpha and TRAIL-induced apoptosis of HeLa cells. Bufotalin
      promoted death receptor-mediated cell death, especially TRAIL-induced apoptosis,
      through activation of caspase-3 and PARP-1. Mitochondrial Bid-dependent pathway
      was activated in TNF-alpha-induced cell death. Cotreatment of bufotalin with
      TRAIL resulted in the downregulation of anti-apoptotic proteins, including Bcl
      XL, Mcl-1, survivin and XIAP, and the up-regulation of MAPKs and TRAIL receptor
      DR5. In addition, phosphorylation of STAT1 was strongly inhibited by bufotalin.
      Moreover, DR5 expression was induced by knocking down the STAT1 expression.
      Moreover, the TRAIL-induced apoptotic response was promoted by STAT1 siRNA. Our
      results demonstrated that bufotalin is a powerful sensitizer of death receptor
      induced apoptosis in cancer cells.

PMID- 21887463
TI  - Transcriptional analysis of CXCR4, DNMT3A, DNMT3B and DNMT1 gene expression in
      primary advanced uterine cervical carcinoma.
AB  - The development of cervical cancer requires genetic and epigenetic factors which
      result in the persistence of a malignant phenotype. Cervical cancer exhibits also
      some unique differences from other solid tumors. Normal cervical stratified
      epithelia have characteristics of hypoxic tissue with over-expression of HIF-1
      (hypoxia-inducible factor-1) transcription factor, which targets the
      transcription of over 70 genes involved in many aspects of cancer biology. One of
      the genes, which could be induced by HIF-1 is chemokine (C-X-C motif) receptor 4
      (CXCR4). CXCR4 could also be epigenetically regulated by methylation of CpG
      dinucleotides located in the promoter region. Here, we examined the CXCR4,
      DNMT3A, DNMT3B and DNMT1 transcript levels in cancer tissue (n=30) and non
      cancer, normal uterine cervical tissue (n=30) from a Polish cohort. We also
      compared the methylation status of CXCR4 promoter region in cancer and normal
      tissue samples. Our result showed significantly higher levels of CXCR4, DNMT3A,
      DNMT3B and DNMT1 transcript (p=0.0058, 0.0163, 0.0003 and <0.0001, respectively)
      levels in cancer tissue as compared to normal samples. We did not observe DNA
      methylation in the CXCR4 promoter region in either control or cancer tissue
      samples. CXCR4 has a functional hypoxia response element (HRE) in the promoter
      region, located -1.3 kb from the transcription start site. Our work shows for the
      first time that HIF-1A could promote the induction of CXCR4 gene expression
      (Spearman's correlation coefficient = 0.515, p=0.003) in patients with primary
      advanced uterine cervical carcinoma.

PMID- 21887464
TI  - Mitomycin C and doxorubicin elicit conflicting signals by causing accumulation of
      cyclin E prior to p21WAF1/CIP1 elevation in human hepatocellular carcinoma cells.
AB  - Proteins involved in the G1 phase of the cell cycle are aberrantly expressed,
      sometimes in mutated forms, in human cancers including human hepatocellular
      carcinoma. Upon attack by a DNA-damaging anticancer drug, a cell arrests at the
      G1 phase; this is a safety feature prohibiting entry of DNA-damaged cells into S
      phase. p21WAF1/CIP1 prevents damaged cells from progressing to the next cell
      cycle. Here, we show that, in response to mitomycin C and doxorubicin, human
      hepatocellular carcinoma cells generate conflicting signals, mediated by cyclin E
      and p21WAF1/CIP1, which respectively accelerates and represses cell cycle
      transition. Exposure to these anticancer drugs led to rapid accumulation of
      cyclin E in both p53-proficient HepG2 and p53-deficient Hep3B cells. Such
      anticancer drug-induced cyclin E accumulation influenced the G1-S-phase
      transition, but not DNA fragmentation-mediated death. In p53-proficient HepG2
      cells, accumulation of cyclin E was followed by an increase in the level of p53
      dependent p21WAF1/CIP1, thereby inhibiting further the G1-S-phase transition.
      Sublethal drug concentrations also induced rapid accumulation of cyclin E, but
      p21WAF1/CIP1 accumulation was delayed, further facilitating the G1-S-phase
      transition. Eventually, most cells arrested in G2/M. Thus, mitomycin C- or
      doxorubicin-induced conflicting signals, mediated by cyclin E and p21WAF1/CIP1,
      are in play in human hepatocellular carcinoma cells. Damaged G1 cells either
      immediately enter S-phase, or do not do so at all, depending on the extent of DNA
      damage.

PMID- 21887465
TI  - Effect of Hedyotis Diffusa Willd extract on tumor angiogenesis.
AB  - Inhibition of tumor angiogenesis has become an attractive target of anticancer
      chemotherapy. However, drug resistance and cytotoxicity against non-tumor
      associated endothelial cells limit the long-term use and the therapeutic
      effectiveness of angiogenesis inhibitors, thus increasing the necessity for the
      development of multi-target agents with minimal side effects. Traditional Chinese
      medicine (TCM) formulas, which have relatively fewer side effects and have been
      used clinically to treat various types of diseases, including cancer, for
      thousands of years, are considered to be multi-component and multi-target agents
      exerting their therapeutic function in a more holistic way. Hedyotis Diffusa
      Willd (EEHDW) has long been used as an important component in several TCM
      formulas to treat various types of cancer. Although recently we reported that
      EEHDW promotes cancer cell apoptosis via activation of the mitochondrial
      dependent pathway, the precise mechanism of its tumoricidalactivity still remains
      to be clarified. In the present study, we investigated the angiogenic effects of
      the ethanol extract of EEHDW. Cell cycle analysis was perfomed using flow
      cytometry. Cell viability was analyzed using MTT assay. We found that EEHDW
      inhibited angiogenesis in vivo in chick embryo chorioallantoic membrane (CAM). In
      addition, we observed that EEHDW dose- and time-dependently inhibited the prolife
      ration of human umbilical vein endothelial cells (HUVEC) by blocking the cell
      cycle G1 to S progression. Moreover, EEHDW inhibited the migration and tube
      formation of HUVECs. Furthermore, EEHDW treatment down-regulated the mRNA and
      protein expression levels of VEGF-A in HT-29 human colon carcinoma cells and
      HUVECs. Our findings suggest that inhibiting tumor angiogenesis is one of the
      mechanisms by which EEHDW is involved in cancer therapy.

PMID- 21887466
TI  - Clinical significance of the expression of DNA methyltransferase proteins in
      gastric cancer.
AB  - DNA methyltransferase (DNMT) 1, DNMT3A and DNMT3B, which affect promoter CpG
      methylation status, play a significant role in cancer development. Little is
      known regarding the clinical significance of DNMT expression in gastric cancers.
      Expression of DNMT1, DNMT3A and DNMT3B in paraffin sections from 54 gastric
      cancer patients were examined using immunohistochemistry, and their associations
      with the corresponding clinicopathological parameters were analyzed using the Chi
      square test. Overexpression of DNMT1, DNMT3A and DNMT3B in gastric cancer tissues
      was observed in 35 (64.8%), 38 (70.4%) and 28 (51.9%) of 54 cases, respectively.
      DNMT1 was localized in the cytoplasm and nuclei of the cancer cells, whereas
      DNMT3A and DNMT3B were detected only in the cytoplasm. DNMT1 expression was more
      frequently found in tumors localizing at the cardia or body of the stomach
      (P=0.048). DNMT3A was associated with TNM stage (P=0.001) and lymph node
      metastasis (P=0.002). No significant correlation was found between DNMT3B
      expression and clinicopathological data (P>0.05). The co-expression of DNMT1 and
      DNMT3A, and of DNMT3A and DNMT3B was more frequently found in tumors localizing
      at the cardia or body of the stomach (P=0.005 and P=0.009 respectively).
      Moreover, co-expression of DNMT1 and DNMT3A was significantly associated with
      lymph node metastasis (P=0.035). DNMTs are overexpressed in gastric cancer, and
      may play a significant role in the development of aberrant promoter methylation
      during tumorigenesis.

PMID- 21887467
TI  - Human papillomavirus prevalence in women with normal cytology and with cervical
      cancer in Natal, Brazil.
AB  - This study analyzed the prevalence of human papillomavirus (HPV) in cervical
      specimens obtained from women with normal cytology and with cervical cancer, in
      order to evaluate their correlation with health status and demographic
      characteristics, as well as sexual and reproductive activity in women treated at
      a cancer reference hospital in Natal, Northeast Brazil. A total of 158 women were
      divided into 2 groups according to their health status: group I comprised 110
      women with normal cytology, and group II comprised 48 women with cervical cancer.
      Cervical smears were analyzed by cytological or histopathological examination for
      the detection of cytological alterations, and by PCR for HPV DNA detection using
      MY09/11 primers, followed by HPV genotyping by dot blot hybridization. Results
      showed overall HPV prevalence to be 24.5% in group I, with 19.1% of patients
      having single infection and 5.4% double infection. The HPV prevalence in group II
      was 85.4%, with 79.2% of patients having single and 6.2% double infection. We
      identified 10 different HPV genotypes, most with high oncogenic potential. HPV 16
      was the most prevalent genotype in the two studied groups, followed by HPV 58 and
      HPV 18. High-risk HPV genital infection, chronological age, ethnicity, early
      onset of sexual and reproductive activities, multiple sexual partners and smoking
      increased the risk for cervical cancer.

PMID- 21887468
TI  - The novel selenium heteropoly compound (NH4)4H4[Se2Mo2V4O24].7H2O induces
      apoptosis of K562 cells.
AB  - The purpose of this study was to investigate the antitumor effects and mechanism
      of the selenium heteropoly compound (NH4)4H4[Se2Mo2V4O24].7H2O (SeMoV) in K562
      cells. The results showed that 0.313-10 mg/l SeMoV significantly inhibited the
      proliferation of K562 cells in vitro in a time- and concentration-dependent
      manner as determined by a micro-culture tetrazolium assay; the IC50 values were
      7.69 and 4.06 mg/l following 48 and 72 h of treatment with SeMoV, respectively.
      Analysis of the cell cycle indicated that the proportion of cells in the G0/G1
      phase was decreased at 48 h whereas the proportion of cells in the S phase was
      increased following treatment for 24 and 48 h. A significant sub-G1 peak was
      observed at 5 mg/l for 24 h. Morphological observation revealed typical apoptotic
      features. SeMoV signifi-cantly caused the accumulation of Ca2+, Mg2+ and ROS, and
      a reduction in the pH value and the mitochondrial membrane potential (MMP) in the
      K562 cells compared with the control (p<0.01), as shown by confocal laser
      scanning microscopy. Experiments also showed that the expression of Bcl-2 was
      significantly inhibited by 20 mg/l SeMoV, while Bax expression increased.
      Meanwhile, the amount of cytochrome C and IkappaB in K562 cells was increased,
      while NF-kappaB expression was significantly decreased, following treatment with
      SeMoV for 24 h. The experiment implied that SeMoV had antitumor activity and its
      mechanism was attributed partially to apoptosis, which was induced by the
      elevation of the intracellular Ca2+, Mg2+ and ROS concentration, a reduction in
      the pH value and MMP, and the NF-kappaB/IkappaB signaling pathway.

PMID- 21887469
TI  - Eag1 potassium channels as markers of cervical dysplasia.
AB  - Human ether a-go-go 1 (Eag1) potassium channels are potential tumor markers and
      therapeutic targets for several types of malignancies, including cervical cancer.
      Estrogens and human papilloma virus oncogenes regulate Eag1 gene expression,
      suggesting that Eag1 may already be present in pre-malignant lesions. Therefore,
      Eag1 could be used as an early marker and/or a potential risk indicator for
      cervical cancer. Consequently, we studied Eag1 protein expression by
      immunochemistry in cervical cancer cell lines, normal keratinocytes, cervical
      cytologies from intraepithelial lesions, biopsies from cervical intraepithelial
      neoplasias (CIN 1, 2 and 3) and in normal smears from patients taking or not
      taking estrogens. Two hundred and eighty-six samples obtained by liquid-based
      cytology and fifteen CIN biopsies were studied. We observed Eag1 protein
      expression in the cervical cancer cell lines, as opposed to normal keratinocytes.
      Eag1 was found in 67% of the cervical cytologies from low-grade intra-epithelial
      lesions and in 92% of the samples from high-grade intraepithelial lesions, but
      only in 27% of the normal samples. Noteworthy, morphologically normal cells
      obtained from dysplastic samples also exhibited Eag1 expression. In CIN biopsies
      we found that the higher the grade of the lesion, the broader the Eag1 protein
      distribution. Almost 50% of the normal patients taking estrogens displayed Eag1
      expression. We suggest Eag1 as a potential marker of cervical dysplasia and a
      risk indicator for developing cervical lesions in patients taking estrogens. Eag1
      detection in cervical cancer screening programs should help to improve early
      diagnosis and decrease mortality rates from this disease.

PMID- 21887471
TI  - Remarkable difference of somatic mutation patterns between oncogenes and tumor
      suppressor genes.
AB  - Cancers arise owing to mutations that confer selective growth advantages on the
      cells in a subset of tumor suppressor and/or oncogenes. To understand oncogenesis
      and diagnose cancers, it is crucial to discriminate these two groups of genes by
      using the difference in their mutation patterns. Here, we investigated>120,000
      mutation samples in 66 well-known tumor suppressor genes and oncogenes of the
      COSMIC database, and found a set of significant differences in mutation patterns
      (e.g., non-3n-indel, non-sense SNP and mutation hotspot) between them. By
      screening the best measurement, we developed indices to readily distinguish one
      from another and predict clearly the unknown oncogenesis genes as tumor
      suppressors (e.g., ASXL1, HNF1A and KDM6A) or oncogenes (e.g., FOXL2, MYD88 and
      TSHR). Based on our results, a third gene group can be classified, which has a
      mutational pattern between tumor suppressors and oncogenes. The concept of the
      third gene group could help to understand gene function in different cancers or
      individual patients and to know the exact function of genes in oncogenesis. In
      conclusion, our study provides further insights into cancer-related genes and
      identifies several potential therapeutic targets.

PMID- 21887470
TI  - pseudo-G-Rh2 induces mitochondrial-mediated apoptosis in SGC-7901 human gastric
      cancer cells.
AB  - This study was designed to investigate the effect of pseudo-G-Rh2, a novel
      metabolite of ginsenoside Rh2, on the apoptosis of SGC-7901 human gastric cancer
      cells. Pseudo-G-Rh2 demonstrated antitumor activity and significantly inhibited
      the proliferation of SGC-7901 cells in a concentration-dependent manner. After
      treatment with pseudo-G-Rh2, SGC-7901 cells showed typical apoptotic
      morphological features, such as chromatin condensation and DNA fragmentation.
      Pseudo-G-Rh2 could induce mitochondrial membrane potential loss, which led to the
      release of cytochrome c (Cyt c), Smac/Diablo and apoptosis-inducing factor (AIF)
      to the cell cytoplasm. Furthermore, pseudo-G-Rh2 exposure not only decreased the
      expression of the Bcl-2 protein but also increased the expression of the Bax
      protein and the activities of caspase-9 and caspase-3 in SGC-7901 cells. These
      results demonstrated that pseudo-G-Rh2 inhibited the proliferation of SGC-7901
      cells by initiating apoptosis. Pseudo-G-Rh2-induced apoptosis was associated with
      a drop in the mitochondrial transmembrane potential, down-regulation of Bcl-2, up
      regulation of Bax and activation of caspase-9 and caspase-3.

PMID- 21887472
TI  - Induction of apoptosis by evodiamine involves both activation of mitotic arrest
      and mitotic slippage.
AB  - Evodiamine (Evo) is an indole quinazoline alkaloid isolated from the fruit of
      Evodia rutaecarpa Bentham. Previous studies have shown that Evo exhibits anti
      proliferative anti-tumor activities in several cancer types, but its target(s)
      and underlying mechanism(s) of action remain unclear. In the present study, we
      sought to establish a cell synchronization model in order to examine the anti
      proliferative and apoptotic mechanisms of Evo in the human gastric cancer cell
      line SGC-7901. In addition, we transfected these cells with full-length or non
      degradable (ND) cyclinB1 to evaluate the relationship between the induction of
      apoptosis and activation of mitotic arrest and mitotic slippage by Evo. Our
      results demonstrated that Evo markedly inhibited cell growth and was cytotoxic to
      SGC-7901 cells. Furthermore, transient Evo treatment (<16 h) caused reversible
      mitotic arrest, but sustained mitotic arrest was required to initiate apoptosis.
      The time required to reverse the apoptotic effects of Evo was between 16 and 20
      h. We also demonstrated that promotion of mitotic slippage by a CDK1 inhibitor
      enhanced apoptosis. Furthermore, we evaluated the effect of delaying mitotic
      slippage by overexpressing ND cyclinB1, which delayed apoptosis. In conclusion,
      these results indicate that Evo-induced apoptosis is associated with mitotic
      arrest and subsequent mitotic slippage, which may underlie the actions of Evo in
      the treatment and prevention of cancer.

PMID- 21887473
TI  - Power Doppler and gray-scale sonography standardized by BI-RADS for the
      differentiation of benign postoperative lesion and local recurrence after breast
      conserving therapy.
AB  - The diagnosis of ipsilateral breast tumor recurrence (IBTR) after breast
      conserving therapy is of great interest to breast physicians. The present study
      compared the utility of gray-scale sonography standardized by a breast imaging
      reporting and data system (BI-RADS) and power Doppler sonography for
      differentiating between benign scar formation and IBTR after breast-conserving
      therapy. Gray-scale sonography detected 83 solid breast lesions classified as BI
      RADS categories 3-5 in 272 patients after breast-conserving therapy, and these
      lesions were entered into the study (53 lesions as category 3, probably benign;
      30 lesions as categories 4-5, suspected malignancy). Power Doppler sonography
      revealed intratumoral flow in 19 of 83 solid breast lesions. BI-RADS category 3
      was accepted as probably benign and BI-RADS categories 4-5 were considered as
      suspicious for breast tumor recurrence in the gray-scale ultrasound criteria.
      Positive and negative intratumoral flow were employed as suspicious for breast
      tumor recurrence and probably benign, respectively, in the power Doppler
      sonography criteria. Sensitivity was higher for power Doppler sonography (94.7+/
      10.0%) than for gray-scale sonography (57.9+/-22.2%). Specificity was also higher
      for power Doppler sonography (98.4+/-3.0%) than for gray-scale sonography (70.3+/
      0.6%). These results suggest that power Doppler sonography can complement gray
      scale sonography standardized by BI-RADS in differentiating between IBTR and
      benign scar lesions.

PMID- 21887474
TI  - Inhibition of STAT3 reverses alkylator resistance through modulation of the AKT
      and beta-catenin signaling pathways.
AB  - Activation of signal transducer and activator of transcription 3 (STAT3) is
      associated with poor clinical outcome of glioblastoma (GBM). However, the role of
      STAT3 in resistance to alkylator-based chemotherapy remains unknown. Here, we
      retrospectively analyzed the phosphorylated STAT3 (p-STAT3) profile of 68 GBM
      patients receiving alkylator therapy, identifying p-STAT3 as an independent
      unfavorable prognostic factor for progression-free and overall survival.
      Additionally, elevated p-STAT3 expression correlated with resistance to alkylator
      therapy. In vitro analysis revealed that U251 and U87 human glioma cells were
      refractory to treatment with the common alkylating agent temozolomide (TMZ), with
      only a modest impact on AKT and beta-catenin activation in the context of high p
      STAT3. Inhibition of STAT3 in these cells significantly enhanced the effect of
      TMZ. Inhibition of STAT3 dramatically decreased the IC50 of TMZ, increasing TMZ
      induced apoptosis while up-regulating expression of Bcl-2 and down-regulating
      expression of Bax. Furthermore, inhibition of STAT3 increased TMZ-induced G0-G1
      arrest and decreased Cyclin D1 expression compared to TMZ alone. Together, these
      results indicate that inhibition of STAT3 sensitizes glioma cells to TMZ, at
      least in part, by blocking the p-AKT and beta-catenin pathways. These findings
      strongly support the hypothesis that STAT3 inhibition significantly improves the
      clinical efficacy of alkylating agents.

PMID- 21887475
TI  - Increased expression of HIF-1A and its implication in the hypoxia pathway in
      primary advanced uterine cervical carcinoma.
AB  - The development of cervical cancer exhibits some unique differences compared to
      other solid tumors. Normal cervical stratified epithelia have characteristics of
      hypoxic tissue. Lack of oxygen (hypoxia) induces the HIF-1 (hypoxia-inducible
      factor-1) transcription factor, which is a heterodimer composed of a
      constitutively expressed beta subunit and a hypoxia-inducible alpha-subunit. HIF
      1A targets the transcription of over 70 genes involved in many aspects of cancer
      biology. In well-oxygenated environments, the HIF-1A subunit is hydroxylated,
      recognized and marked for proteosomal destruction by an E3 ubiquitin ligase, the
      von Hippel-Lindau protein (pVHL) complex. Under hypoxic stress, proline
      hydroxylase (PHD) activity is diminished, and stabilized HIF-1A is involved in
      the activation of the tissue response to hypoxia. Here, we examined the HIF-1A
      and VHL transcript levels and HIF-1A protein levels in cancerous tissue (n=30)
      and non-cancerous, normal uterine cervical tissue (n=30). We also compared the
      methylation status of HIF-1A and of the VHL promoter regions in cancerous and
      normal tissue samples. Significantly higher levels of HIF-1A and VHL transcripts
      (p<0.0001 and p=0.0042, respectively) and of HIF-1A protein (p=0.0037) were
      detected in cancerous tissue compared to normal samples. We did not observe DNA
      methylation in the HIF-1A and VHL promoter region in either control or cancerous
      tissue samples. VHL has a functional hypoxia response element (HRE) in the
      promoter region, and the induction of this HRE acts within a negative feedback
      loop to limit the hypoxic HIF-1A response. Our findings may suggest that HIF-1A
      could promote its own degradation by the induction of VHL gene expression
      (Spearman correlation coefficient, 0.515; p=0.003). Our study shows for the first
      time that this increase in VHL expression could be HIF-1A-dependent and serves
      within a negative feedback pathway during hypoxia to regulate the cell-specific
      oxygen threshold for HIF-1A activation.

PMID- 21887477
TI  - Suppression of Th17 response by Streptococcus thermophilus ST28 through induction
      of IFN-gamma.
AB  - The proinflammatory cytokine interleukin (IL)-17 plays important roles in various
      inflammatory diseases, and IL-17-producing T helper 17 cells (Th17) have received
      much attention. For therapy of Th17-mediated diseases, some reports have
      indicated the clinical efficacy of lactic acid bacteria, including Streptococcus
      thermophilus. In this study, we examined the mechanism for the suppressive
      effects of S. thermophilus ST28 on the Th17 response in murine splenocytes
      stimulated with transforming growth factor (TGF)-beta plus IL-6. Stimulation with
      TGF-beta plus IL-6 increased mRNA expression of IL-17 and its production in the
      splenocytes, but ST28 markedly suppressed both. Meanwhile, ST28 increased the
      mRNA expression of interferon (IFN)-gamma as well as its production. Anti-IFN
      gamma completely cancelled the suppressive effect of ST28 on IL-17 production.
      From these data, it was concluded that IFN-gamma induced by ST28 had an important
      role on the effect. A genomic DNA (10 ug/ml) from ST28 effectively suppressed IL
      17 production, probably via the Toll-like receptor 9. Therefore, modulation of
      Th1/Th17 balance would be one of the mechanisms under which S. thermophilus ST28
      exerts an anti-inflammatory effect.

PMID- 21887476
TI  - Inhibition of experimental auto-immune uveitis by the A3 adenosine receptor
      agonist CF101.
AB  - Uveitis is an inflammation of the middle layer of the eye with a high risk of
      blindness. The Gi protein associated A3 adenosine receptor (A3AR) is highly
      expressed in inflammatory cells whereas low expression is found in normal cells.
      CF101 is a highly specific agonist at the A3AR known to induce a robust anti
      inflammatory effect in different experimental animal models. The CF101 mechanism
      of action entails down-regulation of the NF-kappaB-TNF-alpha signaling pathway,
      resulting in inhibition of pro-inflammatory cytokine production and apoptosis of
      inflammatory cells. In this study the effect of CF101 on the development of
      retinal antigen interphotoreceptor retinoid-binding protein (IRBP)-induced
      experimental autoimmune uveitis (EAU) was assessed. Oral treatment with CF101 (10
      ug/kg, twice daily), initiated upon disease onset, improved uveitis clinical
      score measured by fundoscopy and ameliorated the pathological manifestations of
      the disease. Shortly after treatment with CF101 A3AR expression levels were down
      regulated in the lymph node and spleen cells pointing towards receptor
      activation. Downstream events included a decrease in PI3K and STAT-1 and
      proliferation inhibition of IRPB auto-reactive T cells ex vivo. Inhibition of
      interleukin-2, tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN
      gamma) production and up-regulation of interleukin-10 was found in cultured
      splenocytes derived from CF101-treated animals. Overall, the present study data
      point towards a marked anti-inflammatory effect of CF101 in EAU and support
      further exploration of this small molecule drug for the treatment of uveitis.

PMID- 21887478
TI  - Information theoretic perspective on coastal water-quality monitoring and
      management near an offshore industrial park.
AB  - A semi-continuous water-quality monitoring system was installed in Yunlin
      Offshore Industrial Park (YOIP), the largest industrial park in Taiwan, in 2007
      to provide real-time water-quality information such as pH, water depth, dissolved
      oxygen, temperature, turbidity, conductivity, and chlorophyll. To interpret the
      large quantities of high-frequency data generated by this system, information
      theory was applied for data analysis and extraction of useful information for
      further coastal water-quality management. Information theory is a branch of
      applied mathematics that involves the quantification of information. Shannon
      entropy is a key measure of information that was calculated in this study to
      reveal the inherent uncertainty of water-quality information. The applicability
      of Shannon entropy for signaling possible coastal pollution events in the YOIP
      was explored and results showed that it provides new insight into the inherent
      uncertainty or randomness of the original data. Specially, when Shannon entropy
      was high, multiple instable readings were observed for turbidity and salinity.
      This indicates that Shannon entropy may be a useful new tool for exploratory data
      analysis. It can be used as a supplementary indicator along with the original
      environmental data to signify some episodes of water-quality degradation.

PMID- 21887479
TI  - Mapping forest composition from the Canadian National Forest Inventory and land
      cover classification maps.
AB  - Canada's National Forest Inventory (CanFI) provides coarse-grained, aggregated
      information on a large number of forest attributes. Though reasonably well suited
      for summary reporting on national forest resources, the coarse spatial nature of
      this data limits its usefulness in modeling applications that require information
      on forest composition at finer spatial resolutions. An alternative source of
      information is the land cover classification produced by the Canadian Forest
      Service as part of its Earth Observation for Sustainable Development of Forests
      (EOSD) initiative. This product, which is derived from Landsat satellite imagery,
      provides relatively high resolution coverage, but only very general information
      on forest composition (such as conifer, mixedwood, and deciduous). Here we link
      the CanFI and EOSD products using a spatial randomization technique to distribute
      the forest composition information in CanFI to the forest cover classes in EOSD.
      The resultant geospatial coverages provide randomized predictions of forest
      composition, which incorporate the fine-scale spatial detail of the EOSD product
      and agree in general terms with the species composition summaries from the
      original CanFI estimates. We describe the approach and provide illustrative
      results for selected major commercial tree species in Canada.

PMID- 21887480
TI  - Association between biotic and abiotic parameters and the occurrence of
      cyanobacteria in a Brazilian reservoir.
AB  - The water reservoir of Vargem das Flores, Brazil, has been subject to
      eutrophication problems. The occurrence of cyanobacterial blooms in this water
      body has raised concerns regarding the presence of toxic metabolites. In order to
      understand the factors that promote the proliferation and distribution of
      cyanobacteria in the reservoir, physicochemical parameters, species composition,
      and toxicity of the reservoir water column were analyzed at monthly intervals
      over a 3-year period (2004-2007) using a range of analytical techniques. The
      results showed that cyanobacteria were absent in the dry period, returning after
      the onset of stratification. A succession pattern was observed within this group.
      The Aphanocapsa genus was dominant in the last rainy period of the study (October
      2006 to March 2007). However toxicity was only detected when the genera
      Microcystis and Sphaerocavum were present (October 2005). The principal
      components analysis showed negative correlation between cyanobacteria and
      orthophosphate. The change of dominant cyanobacteria along the 3 years of study
      and the final prevalence of nontoxic genera in the reservoir is an evidence of
      water quality improvement in response to the management techniques implemented in
      the reservoir basin.

PMID- 21887481
TI  - Environmental impact assessment (EIA): an overlooked instrument for sustainable
      development in Pakistan.
AB  - Environmental impact assessment (EIA) is a policy tool used for evaluating a
      project proposal from physical and socioeconomic environmental perspectives. Its
      aim is to reduce the impact of development on environment, hence, ensuring
      environmental sustainability. It is mandatory to submit an Environmental Impact
      Statement before starting a mega project as required by Environmental Protection
      Act of 1997 and Environmental Policy of Pakistan. Public consultation plays a key
      role in an EIA system, identifying the likely aspects and impacts of a
      development activity. This aspect has been ignored in effective enactment of
      environmental legislation in Pakistan. Sufficient legislative instruments are
      there to support EIA system in the country but the agencies responsible for the
      enforcement of environmental regulations have failed to do so. The current
      research gives an insight into the actual status of EIA system in Pakistan along
      with the feedback of EIA specialists and university teachers of the concerned
      departments. A new index has been devised on the basis of questionnaire response
      to work out the overall performance of EIA system in Pakistan or any other
      country. The weaknesses and deficiencies of each EIA stage have been worked out
      for Pakistan and elaborated with the help of the controversial Zero point
      Interchange Project in the capital city of Pakistan.

PMID- 21887482
TI  - Normal mediastinal and hilar lymph nodes in children on multi-detector row chest
      computed tomography.
AB  - OBJECTIVE: To study normal mediastinal and hilar lymph nodes on multi-detector
      chest computed tomography (CT). METHODS: A cohort of 120 children aged 1-17 years
      underwent emergency CT, including the chest, after high-energy trauma. Axial 5-mm
      reconstructions were evaluated for lymph nodes at hilar and various mediastinal
      levels and the short-axis diameters were measured. RESULTS: At least one lymph
      node was found in 115 (96%) children, with subcarinal (69%), lower paratracheal
      (64%) and hilar (60%) nodes being most common. Up to 10 years of age most lymph
      nodes were smaller than or equal to 7 mm. In older children lymph nodes measuring
      up to 10-mm-short-axis diameter were found. Lymph nodes were rare along the
      mammary vessels, at lower oesophageal and at prevascular and posterior
      mediastinal levels in children. CONCLUSION: Mediastinal and hilar lymph nodes are
      more common than previously thought, probably because of increased detection by
      modern multi-detector CT. Lymph node location and age have to be taken into
      account when evaluating lymph nodes in the paediatric chest. Key Points * The
      size and location of normal lymph nodes is of great diagnostic importance * There
      is little relevant published information related to pediatric chest computed
      tomography * We provide normative data concerning mediastinal and hilar lymph
      nodes in children * These normal values can help identify abnormal lymph nodes in
      children.

PMID- 21887483
TI  - Diagnostic accuracy of contrast-enhanced MR angiography and unenhanced proton MR
      imaging compared with CT pulmonary angiography in chronic thromboembolic
      pulmonary hypertension.
AB  - OBJECTIVE: To evaluate the diagnostic accuracy of contrast-enhanced MR
      angiography (CE-MRA) and the added benefit of unenhanced proton MR angiography
      compared with CT pulmonary angiography (CTPA) in patients with chronic
      thromboembolic disease (CTE). METHODS: A 2 year retrospective study of 53
      patients with chronic thromboembolic pulmonary hypertension who underwent CTPA
      and MRI for suspected pulmonary hypertension and a control group of 36 patients
      with no CT evidence of pulmonary embolism. The MRI was evaluated for CTE and the
      combined diagnostic accuracy of ce-MRA and unenhanced proton MRA was determined.
      CE-MRA generated lung perfusion maps were also assessed. RESULTS: The overall
      sensitivity and specificity of CE-MRA in diagnosing proximal and distal CTE were
      98% and 94%, respectively. The sensitivity improved from 50% to 88% for central
      vessel disease when CE-MRA images were analysed with unenhanced proton MRA. The
      CE-MRA identified more stenoses (29/18), post-stenosis dilatation (23/7) and
      occlusions (37/29) compared with CTPA. The CE-MRA perfusion images showed a
      sensitivity of 92% for diagnosing CTE. CONCLUSION: CE-MRA has high sensitivity
      and specificity for diagnosing CTE. The sensitivity of CE-MRA for visualisation
      of adherent central and lobar thrombus significantly improves with the addition
      of unenhanced proton MRA which delineates the vessel wall.

PMID- 21887484
TI  - Diagnosis of bone metastases: a meta-analysis comparing 18FDG PET, CT, MRI and
      bone scintigraphy.
AB  - OBJECTIVE: To perform a meta-analysis to compare (18)FDG PET, CT, MRI and bone
      scintigraphy (BS) for the diagnosis of bone metastases. METHODS: Databases
      including MEDLINE and EMBASE were searched for relevant original articles
      published from January 1995 to January 2010. Software was used to obtain pooled
      estimates of sensitivity, specificity and summary receiver operating
      characteristic curves (SROC). RESULTS: 67 articles consisting of 145 studies
      fulfilled all inclusion criteria. On per-patient basis, the pooled sensitivity
      estimates for PET, CT, MRI and BS were 89.7%, 72.9%, 90.6% and 86.0%
      respectively. PET=MRI>BS>CT. ("="indicated no significant difference, P > 0.05;
      ">" indicated significantly higher, P < 0.05). The pooled specificity estimates
      for PET, CT, MRI and BS were 96.8%, 94.8%, 95.4% and 81.4% respectively. PET = CT
      = MRI>BS. On per-lesion basis, the pooled sensitivity estimates for PET, CT, MRI
      and BS were 86.9%, 77.1%, 90.4% and 75.1% respectively. PET = MRI>BS>CT. The
      pooled specificity estimates for PET, CT, MRI and BS were 97.0%, 83.2%, 96.0% and
      93.6% respectively. PET>MRI>BS>CT. CONCLUSION: PET and MRI were found to be
      comparable and both significantly more accurate than CT and BS for the diagnosis
      of bone metastases.

PMID- 21887485
TI  - Dabigatran: review of pharmacology and management of bleeding complications of
      this novel oral anticoagulant.
AB  - Dabigatran (Pradaxa) is a competitive direct thrombin inhibitor approved by the
      US FDA for prevention of embolic stroke in patients with nonvalvular atrial
      fibrillation. Dabigatran has a pharmacokinetic profile that produces predictable
      anticoagulation responses, does not undergo CYP 450 metabolism, has few drug-drug
      and drug-food interactions, and does not require frequent laboratory monitoring
      of clotting parameters. Clinicians are rapidly prescribing this agent as a
      replacement for warfarin therapy. However, no therapeutic agent has been accepted
      to reliably reverse the hemorrhagic complications of dabigatran. As of yet, there
      is no solid evidence to guide management of bleeding complications; management
      should start with local control of bleeding when possible and transfusion of
      pRBCs if needed. Transfusion of FFP would not be expected to help control
      bleeding. Limited and mixed data exist for transfusion of factor VIIa and
      prothrombin complex concentrates; these therapies should be considered as well as
      dialysis, which will increase elimination in patients with life-threatening or
      closed-space bleeding due to dabigatran. We present an article that reviews the
      pharmacokinetics, clinical trial literature, and consensus guidelines regarding
      this novel oral anticoagulant.

PMID- 21887487
TI  - Estimation of BVAS in patients with microscopic polyangiitis in Japan.
AB  - The validity of the Birmingham Vasculitis Activity Score (BVAS) as an index of
      disease activity and a predictor of the prognosis and outcome in patients with
      MPA has not yet been established in Japan. We conducted a retrospective study of
      the data of 73 patients with MPA who were followed up for at least 2 years. We
      divided the patients into two groups according to the BVAS, namely, the high-BVAS
      group (>=16) and the low-BVAS group (<16), and compared the clinical
      characteristics. In addition, the distribution of the BVAS items in the patients
      and the items contributing to the total score in MPA patients were analyzed.
      Remission was achieved in 85% of patients at 1 month. There were no significant
      differences in the serum CRP, creatinine (Cre), or MPO-ANCA between the high- and
      low-BVAS group; however, the survival time was significantly shorter (p = 0.048)
      and the mortality rate significantly higher in the high-BVAS group (p = 0.04).
      The items of the BVAS contributing to the total score were motor neuropathy,
      sensory neuropathy, pulmonary infiltrate, hematuria, proteinuria, Cre >=5.6
      mg/dL, hypertension, scleritis, rise in Cre by >=30%, and myalgia. BVAS was found
      to be a useful tool for determining the disease activity and outcome in patients
      with MPA in Japan. The initial BVAS was also predictive of the mortality and
      survival time and can also be used as a prognostic tool; therefore, use of the
      tool may facilitate the selection of appropriate treatment.

PMID- 21887486
TI  - BRCA1-mediated signaling pathways in ovarian carcinogenesis.
AB  - The link between loss or defect in functional BRCA1 and predisposition for
      development of ovarian and breast cancer is well established. Germ-line mutations
      in BRCA1 are responsible for both hereditary breast and ovarian cancer, which is
      around 5-10% for all breast and 10-15% of all ovarian cancer cases. However,
      majority of cases of ovarian cancer are sporadic in nature. The inactivation of
      cellular BRCA1 due to mutations or loss of heterozygosity is one of the most
      commonly observed events in such cases. Complement-resistant retroviral BRCA1
      vector, MFG-BRCA1, is the only approved gene therapy for ovarian cancer patients
      by the Federal and Drug Administration. Given the limited available information,
      there is a need to evaluate the effects of BRCA1 on the global gene expression
      pattern for better understanding the etiology of the disease. Here, we use
      Ingenuity Pathway Knowledge Base to examine the differential pattern of global
      gene expression due to stable expression of BRCA1 in the ovarian cancer cell
      line, SKOV3. The functional analysis detected at least five major pathways that
      were significantly (p < 0.05) altered. These include: cell to cell signaling and
      interaction, cellular function and maintenance, cellular growth and
      proliferation, cell cycle and DNA replication, and recombination repair. In
      addition, we were able to detect several biologically relevant genes that are
      central for various signaling networks involved in cellular homeostasis; TGF
      beta1, TP53, c-MYC, NF-kappaB and TNF-alpha. This report provides a comprehensive
      rationale for tumor suppressor function(s) of BRCA1 in ovarian carcinogenesis.

PMID- 21887488
TI  - "Beating osteoARThritis": development of a stepped care strategy to optimize
      utilization and timing of non-surgical treatment modalities for patients with hip
      or knee osteoarthritis.
AB  - Inadequacies in health care practices have been reported despite existing
      guidelines to manage hip or knee osteoarthritis. To facilitate guideline
      implementation and improve utilization of non-surgical treatment options a care
      strategy should be developed. This study describes the development of an evidence
      based, multidisciplinary, patient-centered, stepped care strategy. A national,
      multidisciplinary, steering group developed the strategy in three phases: (1)
      consensus among steering group members (first draft); (2) written consultation of
      23 representatives of patient organizations and professional associations
      involved in osteoarthritis care (second draft); (3) consensus of the final draft
      after discussion in two rounds during a conference with representatives from the
      different disciplines. The final stepped care strategy presents, in three tiers,
      the optimal order for non-surgical treatment modalities. It recommends that more
      advanced options should only be considered if options listed in previous steps
      failed to produce satisfactory results. Hence, the first step treatment options
      can be offered to all patients but may also be provided through self care
      (education, life style advice, and acetaminophen). The second step (exercise
      therapy, dietary therapy, and non-steroidal anti-inflammatory drugs) and third
      step treatment options (multidisciplinary care, intra-articular injections, and
      transcutaneous electrical nerve stimulation) can be considered for people with
      persisting complaints. Trough a consensus procedure, we succeeded to develop a
      multidisciplinary, patient-centered, stepped care strategy based on national
      guidelines. This strategy provides a framework for health care providers and
      patients with hip or knee osteoarthritis to discuss the optimal timing of the
      various treatment options.

PMID- 21887489
TI  - The relationship between physical activity level, anxiety, depression, and
      functional ability in children and adolescents with juvenile idiopathic
      arthritis.
AB  - The aim of this study was to assess the relationships between physical activity
      level and anxiety, depression, and functional ability in children and adolescents
      with juvenile idiopathic arthritis (JIA). Cross-sectional study design including
      patients with JIA aged between 8 and 17 years and healthy controls was used.
      Sociodemographic data and clinical features were assessed. Physical activity
      level and energy expenditure were assessed with a 1-day activity diary. Anxiety
      was screened by The Screen for Child Anxiety Related Emotional Disorders (SCARED)
      questionnaire. Depressive symptoms were assessed by the Children's Depression
      Inventory (CDI). Functional ability was assessed with the Childhood Health
      Assessment Questionnaire (CHAQ). Pain and overall well-being were measured using
      a visual analog scale (VAS). Fifty-two patients and 48 controls were included
      with a mean age of 12.13 +/- 2.92 and 11.27 +/- 1.59 years, respectively. The
      mean disease duration was 64 months. The JIA group had significantly less time in
      physical activity (p = 0.000), decrease in energy expenditure (p = 0.04), and
      higher CHAQ scores (p = 0.000) compared with the control group. In the JIA group,
      significant relationships were found between the number of active joint and
      disease duration (r = 0.44, p = 0.000) and VAS pain (r = 0.30, p = 0.02), between
      SCARED and CDI (r = 0.54, p = 0.000). Significant relationships were found
      between VAS overall well-being and CDI (r = 0.29, p = 0.03), CHAQ (r = 0.37, p =
      0.000), and VAS pain (r = 0.41, p = 0.000). Correlation between CHAQ and CDI (r =
      0.34, p = 0.01) was significant. The result of our study suggested that only
      depression was related to anxiety, functional ability, and well-being in children
      and adolescents with JIA.

PMID- 21887491
TI  - P2X receptor homologs in basal fungi.

PMID- 21887490
TI  - Rheumatoid arthritis in Burkina Faso: clinical and serological profiles.
AB  - The objective of this work was to study the clinical and serological profiles of
      rheumatoid arthritis in Burkina Faso (West Africa). It is a cross-sectional study
      conducted from March 2006 to February 2009 in the Internal Medicine Department of
      the University Hospital Yalgado Ouedraogo. All patients seen in the rheumatologic
      consultation unit during this period, with rheumatoid arthritis fulfilling the
      ACR criteria, were routinely selected. The determination of anticyclic
      citrullinated peptide antibodies (ACPA) was carried out with a computerized
      method (Elia CCP, Phadia AB, Uppsala, Sweden). Values higher than 10 IU/l were
      considered positive. Forty-eight cases of rheumatoid arthritis (RA) were
      recruited throughout the study period among 2,194 (2.2 %) patients. Forty-two
      files were subjected to the study. There were 34 women and 8 men. The average age
      was 41.70 +/- 13 years with extremes of 22 and 71 years. The average duration of
      the disease was 86.17 +/- 82.01 months with extremes of 8 and 360 months.
      Rheumatoid factors (RF) were positive in 21 out of 30 patients (70.0%). The
      determination of ACPA carried out in all the patients was positive in 34 (81%)
      patients; their average value was 217 IU/l with extremes of 38 and 1,170. RF and
      ACPA were associated to bones erosions (p = 0.0001). Twenty-two patients were
      placed on methotrexate, eight on hydroxychloroquine, and three on salazopyrine.
      Nine were given only NSAIDs or prednisolone. No patients had had a biotherapy
      agent. The frequency of RA was low in our study compared to other African studies
      published so far. The particularity of RA cases reported in African series,
      including ours, is the rarity of extra-articular manifestations of the disease.
      The severity of the disease at presentation in the rheumatology clinic may be due
      to their late consultation among other causes.

PMID- 21887493
TI  - Multifocal meningeal melanocytoma of the conus medullaris.

PMID- 21887494
TI  - Hemifacial spasm can be the presenting symptom of a fourth ventricle tumour. A
      short case-illustrated review and pathogenetic considerations.
AB  - In this short case-illustrated review we aimed to analyse the possible nuances of
      hemifacial spasm (HFS) as the presenting symptom of a tumour of the fourth
      ventricle. The issue is remarkable since HFS can be secondary to a fourth
      ventricle tumour, even when no other neurological signs are reported. In
      addition, the possible presentation with only upper facial muscle involvement, as
      in the presented case, can be deceitful because this is characteristic of the
      benign and much more frequent "typical" form. Based on our intra-operative data
      and on the previously reported cases, we think that pathogenesis could be
      referable to the facial nerve nucleus involvement and that clinical nuances could
      be related to the specific somatotropy of the nucleus under the fourth ventricle
      floor that, as in our case, can be infiltrated by tumour. Resolution of the
      disorder can usually be obtained after the complete resection of the tumour that
      in the reported case resulted a subependymoma (WHO grade I), so far never
      described in literature associated with HFS.

PMID- 21887492
TI  - Interaction of purinergic receptors with GPCRs, ion channels, tyrosine kinase and
      steroid hormone receptors orchestrates cell function.
AB  - Extracellular purines and pyrimidines have emerged as key regulators of a wide
      range of physiological and pathophysiological cellular processes acting through
      P1 and P2 cell surface receptors. Increasing evidence suggests that purinergic
      receptors can interact with and/or modulate the activity of other classes of
      receptors and ion channels. This review will focus on the interactions of
      purinergic receptors with other GPCRs, ion channels, receptor tyrosine kinases,
      and steroid hormone receptors. Also, the signal transduction pathways regulated
      by these complexes and their new functional properties are discussed.

PMID- 21887495
TI  - Pregabalin reduces alcohol drinking and relapse to alcohol seeking in the rat.
AB  - RATIONALE: Pregabalin (LyricaTM) is a structural analogue of gamma-aminobutyric
      acid (GABA) approved by FDA for partial epilepsy, neuropathic pain and recently
      generalized anxiety disorder. While the exact cellular mechanism of action of
      pregabalin is still unclear, evidence from several studies suggests that it
      reduces excitatory neurotransmitter release and postsynaptic excitability.
      OBJECTIVES: Based on these mechanisms we sought interesting to evaluate the
      effect of pregabalin on alcohol-abuse-related behaviours. MATERIALS AND METHODS:
      For this purpose, using genetically selected alcohol-preferring Marchigian
      Sardinian (msP) rats, we evaluated the effect of pregabalin on alcohol drinking
      and relapse to alcohol seeking elicited by environmental conditioning factors or
      stress. RESULTS: Our results showed that treatment with pregabalin (0, 10, 30 and
      60 mg/kg) given orally selectively reduced home cage alcohol drinking in msP rat.
      This effect was confirmed in self-administration experiments where pregabalin (0,
      10 and 30 mg/kg) significantly reduced operant responding for alcohol but not for
      food. Using alcohol reinstatement models we also found that pregabalin (0, 10 and
      30 mg/kg) abolished seeking behaviour elicited by the pharmacological stressor
      yohimbine as well as cues predictive of alcohol availability. CONCLUSIONS:
      Results demonstrate that pregabalin may have potential in the treatment of
      alcohol addiction.

PMID- 21887496
TI  - Environmental-induced differences in corticosterone and glucocorticoid receptor
      blockade of amphetamine self-administration in rats.
AB  - RATIONALE: Rats raised in isolation self-administer more amphetamine than rats
      raised in enrichment. OBJECTIVE: This study examined whether differential rearing
      alters basal and amphetamine-stimulated corticosterone and whether blocking
      glucocorticoid receptors alters amphetamine self-administration in differentially
      reared rats. METHODS: The rats were raised from 21 to 51 days of age in either an
      enriched condition (EC), social condition (SC), or isolated condition (IC).
      Following the repeated collection of basal blood samples, the rats were
      administered amphetamine (0.5 or 2.0 mg/kg, i.p.) or saline, and blood samples
      were collected again. In another experiment, EC and IC rats were trained to i.v.
      self-administer amphetamine (0.003 or 0.03 mg/kg/infusion) and then were
      pretreated with the glucocorticoid receptor antagonist RU-486 (5, 10, or 20
      mg/kg; i.p.) or vehicle prior to the session. RESULTS: Basal-free corticosterone
      levels were ~4 times higher in IC rats than in either EC or SC rats with the
      first blood collection, but not with repeated collections. IC rats showed a more
      rapid amphetamine-induced increase in corticosterone levels than EC and SC rats.
      RU-486 pretreatment decreased amphetamine self-administration dose-dependently in
      both EC and IC rats; however, using an amphetamine unit dose of 0.03
      mg/kg/infusion, the effect of RU-486 was blunted in IC rats (maximal decrease of
      ~40% in IC and ~90% in EC), suggesting an environment-induced difference in the
      role of glucocorticoid receptors in stimulant reinforcement. CONCLUSION: The
      increase in stimulant self-administration produced by social isolation may
      involve enhanced reactivity of the hypothalamo-pituitary-adrenal stress axis.

PMID- 21887497
TI  - Attenuation of cocaine-induced conditioned locomotion is associated with altered
      expression of hippocampal glutamate receptors in mice lacking LPA1 receptors.
AB  - RATIONALE: Lysophosphatidic acid is a phospholipid mediator that modulates
      neurodevelopment and neurogenesis in the hippocampus through its actions on LPA1
      receptors. Emerging evidences support LPA(1) as a mediator of learning and
      emotional behaviour. There are no studies addressing its role on behaviours
      associated to drug abuse. OBJECTIVES: We examined whether genetic deletion of
      LPA1 receptor in maLPA(1)-null mice affected either cocaine-induced conditioned
      locomotion (CL) or behavioural sensitization (BS) induced by repeated cocaine
      exposure. We also analysed whether cocaine induced changes in the expression of
      functional markers of both dopamine- and glutamate-related genes in the striatum
      and the dorsal hippocampus. METHODS: We monitored cocaine-induced CL and BS in
      both genotypes of mice. Striatal dopamine and hippocampal glutamate-related genes
      were measured by real-time quantitative PCR, Western blot, and
      immunohistochemistry. RESULTS: maLPA(1)-null mice exhibit an attenuated CL
      response after cocaine conditioning but a normal BS after repeated cocaine
      exposure. These behavioural changes were associated to alterations on the
      expression of metabotropic mGLUR3 glutamate receptors and on the actions of
      cocaine on the GLUR1 subunit of AMPA glutamate receptors in the hippocampus of
      maLPA(1) animals. Striatal dopaminergic markers (tyrosine hydroxylase, dopamine
      D1 receptor, and dopamine transporter DAT), were similar in both genotypes and
      were equally affected by cocaine exposure. CONCLUSION: The present results
      indicate that the lack of LPA1 receptor affect cocaine-induced conditioned
      locomotion but not behavioural sensitization. The findings suggest that LPA1
      receptor may be necessary for a normal associative contextual learning associated
      to cocaine, probably through the modulation of hippocampal glutamatergic
      circuits.

PMID- 21887498
TI  - Unidirectional relationship between heroin self-administration and impulsive
      decision-making in rats.
AB  - RATIONALE: There is growing clinical evidence for a strong relationship between
      drug addiction and impulsivity. However, it is not fully clear whether
      impulsivity is a pre-existing trait or a consequence of drug abuse. Recent
      observations in the animal models show that pre-existing levels of impulsivity
      predict cocaine and nicotine seeking. Whether such relationships also exist with
      respect to non-stimulant drugs is largely unknown. OBJECTIVE: We studied the
      relationship between impulsive choice and vulnerability to heroin taking and
      seeking. MATERIALS AND METHODS: Rats were selected in the delayed reward task
      based on individual differences in impulsive choice. Subsequently, heroin
      intravenous self-administration behaviour was analysed, including acquisition of
      heroin intake, motivation, extinction and drug- and cue-induced reinstatement.
      Throughout the entire experiment, changes in impulsive choice were monitored
      weekly. RESULTS AND DISCUSSION: High impulsivity did not predict measures of
      heroin taking. Moreover, high impulsive rats did not differ from low impulsive
      rats in extinction rates or heroin- and cue-induced reinstatement. However, both
      groups became more impulsive as heroin self-administration continued. During
      abstinence, impulsivity levels returned towards baseline (pre-heroin) levels. Our
      results indicate that, in contrast to psychostimulants, impulsive choice does not
      predict vulnerability to heroin seeking and taking. CONCLUSION: These data
      implicate that different neural mechanisms may underlie the vulnerability to
      opiate and psychostimulant dependence. Moreover, our data suggest that elevated
      impulsivity levels as observed in heroin-dependent subjects are a consequence of
      heroin intake rather than a pre-existing vulnerability trait.

PMID- 21887499
TI  - A model for complex sequence learning and reproduction in neural populations.
AB  - Temporal patterns of activity which repeat above chance level in the brains of
      vertebrates and in the mammalian neocortex have been reported experimentally.
      This temporal structure is thought to subserve functions such as movement,
      speech, and generation of rhythms. Several studies aim to explain how particular
      sequences of activity are learned, stored, and reproduced. The learning of
      sequences is usually conceived as the creation of an excitation pathway within a
      homogeneous neuronal population, but models embodying the autonomous function of
      such a learning mechanism are fraught with concerns about stability, robustness,
      and biological plausibility. We present two related computational models capable
      of learning and reproducing sequences which come from external stimuli. Both
      models assume that there exist populations of densely interconnected excitatory
      neurons, and that plasticity can occur at the population level. The first model
      uses temporally asymmetric Hebbian plasticity to create excitation pathways
      between populations in response to activation from an external source. The
      transition of the activity from one population to the next is permitted by the
      interplay of excitatory and inhibitory populations, which results in oscillatory
      behavior that seems to agree with experimental findings in the mammalian
      neocortex. The second model contains two layers, each one like the network used
      in the first model, with unidirectional excitatory connections from the first to
      the second layer experiencing Hebbian plasticity. Input sequences presented in
      the second layer become associated with the ongoing first layer activity, so that
      this activity can later elicit the the presented sequence in the absence of
      input. We explore the dynamics of these models, and discuss their potential
      implications, particularly to working memory, oscillations, and rhythm
      generation.

PMID- 21887500
TI  - A phase IIa randomized controlled pilot study evaluating the safety and clinical
      outcomes following the use of rhGDF-5/beta-TCP in regenerative periodontal
      therapy.
AB  - To present the safety profile, the early healing phase and the clinical outcomes
      at 24 weeks following treatment of human intrabony defects with open flap
      debridement (OFD) alone or with OFD and rhGDF-5 adsorbed onto a particulate beta
      tricalcium phosphate (beta-TCP) carrier. Twenty chronic periodontitis patients,
      each with at least one tooth exhibiting a probing depth >=6 mm and an associated
      intrabony defect >=4 mm entered the study. Ten subjects (one defect/patient) were
      randomized to receive OFD alone (control) and ten subjects OFD combined with
      rhGDF-5/beta-TCP. Blood samples were collected at screening, and at weeks 2 and
      24 to evaluate routine hematology and clinical chemistry, rhGDF-5 plasma levels,
      and antirhGDF-5 antibody formation. Plaque and gingival indices, bleeding on
      probing, probing depth, clinical attachment level, and radiographs were recorded
      pre- and 24 weeks postsurgery. Comparable safety profiles were found in the two
      treatment groups. Neither antirhGDF-5 antibody formation nor relevant rhGDF-5
      plasma levels were detected in any patient. At 6 months, treatment with OFD +
      rhGDF-5/beta-TCP resulted in higher but statistically not significant PD
      reduction (3.7 +/- 1.2 vs. 3.1 +/- 1.8 mm; p = 0.26) and CAL gain (3.2 +/- 1.7
      vs. 1.7 +/- 2.2 mm; p = 0.14) compared to OFD alone. In the tested concentration,
      the use of rhGDF-5/beta-TCP appeared to be safe and the material possesses a
      sound biological rationale. Thus, further adequately powered, randomized
      controlled clinical trials are warranted to confirm the clinical relevance of
      this new approach in regenerative periodontal therapy. rhGDF-5/beta-TCP may
      represent a promising new techology in regenerative periodontal therapy.

PMID- 21887501
TI  - Eribulin mesylate in patients with refractory cancers: a Phase I study.
AB  - Eribulin mesylate (HalavenTM, E7389) is a synthetic analog of the marine natural
      product halichondrin B that acts via a mechanism distinct from conventional
      tubulin-targeted agents. This Phase I study (clinicaltrials.gov identifier:
      NCT00326950) was the first to investigate eribulin mesylate in Japanese patients.
      The study determined the recommended dose, MTD, DLTs, safety, pharmacokinetics,
      and antitumor activity of eribulin administered on Days 1 and 8 of a 21-day cycle
      in Japanese patients with advanced solid tumors. Fifteen patients received
      eribulin mesylate 0.7-2.0 mg/m(2) as a 2- to 10-min intravenous injection.
      Neutropenia was the principal DLT. DLTs were observed in two of six patients
      treated at 1.4 mg/m(2), and in all three patients at 2.0 mg/m(2). The recommended
      dose was 1.4 mg/m(2) and the MTD was 2.0 mg/m(2). Neutropenia (67%),
      lymphocytopenia (20%), febrile neutropenia (33%), and fatigue (13%) were the most
      common grade 3 or 4 toxicities. Eribulin exhibited triphasic pharmacokinetics
      with a long terminal half-life, high volume of distribution, and low urinary
      clearance. Three patients achieved partial responses (two with NSCLC, one with
      head and neck cancer) at 1.4 mg/m(2) dose level. Eribulin mesylate, administered
      on Days 1 and 8 of a 21-day cycle, exhibits manageable tolerability at 1.4
      mg/m(2). DLT was neutropenia.

PMID- 21887502
TI  - The cytotoxic activity of Aplidin in chronic lymphocytic leukemia (CLL) is
      mediated by a direct effect on leukemic cells and an indirect effect on monocyte
      derived cells.
AB  - Aplidin is a novel cyclic depsipeptide, currently in Phase II/III clinical trials
      for solid and hematologic malignancies. The aim of this study was to evaluate the
      effect of Aplidin in chronic lymphocytic leukemia (CLL), the most common leukemia
      in the adult. Although there have been considerable advances in the treatment of
      CLL over the last decade, drug resistance and immunosuppression limit the use of
      current therapy and warrant the development of novel agents. Here we report that
      Aplidin induced a dose- and time-dependent cytotoxicity on peripheral blood
      mononuclear cells (PBMC) from CLL patients. Interestingly, Aplidin effect was
      markedly higher on monocytes compared to T lymphocytes, NK cells or the malignant
      B-cell clone. Hence, we next evaluated Aplidin activity on nurse-like cells (NLC)
      which represent a cell subset differentiated from monocytes that favors leukemic
      cell progression through pro-survival signals. NLC were highly sensitive to
      Aplidin and, more importantly, their death indirectly decreased neoplasic clone
      viability. The mechanisms of Aplidin-induced cell death in monocytic cells
      involved activation of caspase-3 and subsequent PARP fragmentation, indicative of
      death via apoptosis. Aplidin also showed synergistic activity when combined with
      fludarabine or cyclophosphamide. Taken together, our results show that Aplidin
      affects the viability of leukemic cells in two different ways: inducing a direct
      effect on the malignant B-CLL clone; and indirectly, by modifying the
      microenvironment that allows tumor growth.

PMID- 21887503
TI  - Bone targeted therapies in early breast cancer.
AB  - OPINION STATEMENT: Bisphosphonates have emerged as an important tool in the
      supportive care of women with early breast cancer. Whereas traditionally, these
      drugs have been part of the treatment of osseous metastasis, the key role of
      bisphosphonates in preserving bone health in patients with early breast cancer
      cannot be overemphasised. Currently the most established use of bisphosphonates
      in early breast cancer patients is in women receiving hormonal blockade, mostly
      aromatase inhibitors (AI), with concomitant osteopenia. To that end, it is
      recommended that every woman undergo a Dual Energy X-Ray absorptiometry (DEXA)
      scan before commencement of an AI and annually during the treatment duration. In
      addition, unless contraindicated, all women should receive calcium and Vitamin D
      supplementation. The use of bisphosphonates as part of the adjuvant therapy
      strategy, regardless of baseline bone density condition, has produced thought
      provoking results, although this is not yet considered standard clinical
      practise.

PMID- 21887504
TI  - Time for endothelial cell proprotein convertase PC5/6 in cardiovascular medicine?

PMID- 21887505
TI  - Involvement of TNFalpha-induced TLR4-NF-kappaB and TLR4-HIF-1alpha feed-forward
      loops in the regulation of inflammatory responses in glioma.
AB  - The precise role of different toll-like receptor (TLR) superfamily members is
      just beginning to get elucidated in glioblastoma multiforme (GBM). In this study,
      we observed heightened TLR4 levels in GBM tumor samples as compared to adjacent
      normal tissue. Since the pro-inflammatory cytokine tumor necrosis factor
      (TNF)alpha induces NF-kappaB activation in GBM, and as several common signaling
      mediators are involved in TNFalpha and TLR4-mediated NF-kappaB activation, we
      investigated the role of TLR4 in the regulation of NF-kappaB activation and
      inflammatory responses in TNFalpha-treated glioma cells. TNFalpha elevated TLR4
      expression and inhibition of TLR4 signaling by either signaling inhibitor,
      neutralizing antibody, or small interfering RNA (siRNA)-attenuated TNFalpha
      induced NF-kappaB activation. TLR4-mediated NF-kappaB activation was independent
      of canonical myeloid differentiation factor 88 signaling but involved toll/IL-1R
      homology domain-containing adaptor protein-inducing interferon-beta. Inhibition
      of TLR4 signaling abrogated TNFalpha-induced increase in (1) transcription
      factors interferon (IFN) regulatory factor 3 and STAT-1 and (2) IFNbeta and
      inflammatory cytokines/chemokines expression. Furthermore, TNFalpha-induced TLR4
      dependent increase in AKT activation and HIF-1alpha transcriptional activation
      suggested the existence of TLR4-AKT-HIF-1alpha axis. Importantly, TNFalpha
      induced TLR4 was abrogated in cells transfected with dominant negative IkappaB
      and HIF-1alpha siRNA. Our studies indicate that TNFalpha triggered TLR4-HIF
      1alpha and NF-kappaB-TLR4 feed-forward loops act in tandem to sustain
      inflammatory response in glioma.

PMID- 21887506
TI  - Combined strategy for fertility preservation in an oncologic patient:
      vitrification of in vitro matured oocytes and ovarian tissue freezing.

PMID- 21887507
TI  - Characteristic features and biotechnological applications of cross-linked enzyme
      aggregates (CLEAs).
AB  - Cross-linked enzyme aggregates (CLEAs) have many economic and environmental
      benefits in the context of industrial biocatalysis. They are easily prepared from
      crude enzyme extracts, and the costs of (often expensive) carriers are
      circumvented. They generally exhibit improved storage and operational stability
      towards denaturation by heat, organic solvents, and autoproteolysis and are
      stable towards leaching in aqueous media. Furthermore, they have high catalyst
      productivities (kilograms product per kilogram biocatalyst) and are easy to
      recover and recycle. Yet another advantage derives from the possibility to co
      immobilize two or more enzymes to provide CLEAs that are capable of catalyzing
      multiple biotransformations, independently or in sequence as catalytic cascade
      processes.

PMID- 21887508
TI  - Site-specific genome integration in alphaproteobacteria mediated by TG1
      integrase.
AB  - The serine-type phage integrase is an enzyme that catalyzes site-specific
      recombination between two attachment sites of phage and host bacterial genomes
      (attP and attB, respectively) having relatively short but distinct sequences
      without host auxiliary factor(s). Previously, we have established in vivo and in
      vitro site-specific recombination systems based on the serine-type integrase
      produced by actinophage TG1 and determined the minimal sizes of attP(TG1) and
      attB(TG1) sites required for the in vitro TG1 integrase reaction as 43- and 39
      bp, respectively. Here, DNA databases were surveyed by FASTA program with the
      authentic attB(TG1) sequence of Streptomyces avermitilis as a query. As a result,
      possible attB(TG1) sequences were extracted from genomes of bacterial strains
      belonging to Class Alphaproteobacteria in addition to those of Class
      Actinobacteria. Those sequences extracted with a high similarity score and high
      sequence identity (we took arbitrarily more than 80% identity) turned out to be
      located within a conserved region of dapC or related genes encoding
      aminotransferases and proved to be actually recognized as the cognate substrate
      of attP(TG1) site by the in vitro TG1 integrase assay. Furthermore, the possible
      attB(TG1) site of Rhodospirillum rubrum revealed to be used actually as a native
      (endogenous) attachment site for the in vivo TG1-based integration system. These
      features are distinct from other serine-type phage integrases and advantageous
      for a tool of genome technology in varied industrially important bacteria
      belonging to Class Alphaproteobacteria.

PMID- 21887509
TI  - Resveratrol alters microRNA expression profiles in A549 human non-small cell lung
      cancer cells.
AB  - Resveratrol is a plant phenolic phytoalexin that has been reported to have
      antitumor properties in several types of cancers. In particular, several studies
      have suggested that resveratrol exerts antiproliferative effects against A549
      human non-small cell lung cancer cells; however, its mechanism of action remains
      incompletely understood. Deregulation of microRNAs (miRNAs), a class of small,
      noncoding, regulatory RNA molecules involved in gene expression, is strongly
      correlated with lung cancer. In this study, we demonstrated that resveratrol
      treatment altered miRNA expression in A549 cells. Using microarray analysis, we
      identified 71 miRNAs exhibiting greater than 2-fold expression changes in
      resveratrol-treated cells relative to their expression levels in untreated cells.
      Furthermore, we identified target genes related to apoptosis, cell cycle
      regulation, cell proliferation, and differentiation using a miRNA target
      prediction program. In conclusion, our data demonstrate that resveratrol induces
      considerable changes in the miRNA expression profiles of A549 cells, suggesting a
      novel approach for studying the anticancer mechanisms of resveratrol.

PMID- 21887510
TI  - Auditory function in individuals within Leber's hereditary optic neuropathy
      pedigrees.
AB  - The aims of this study are to investigate whether auditory dysfunction is part of
      the spectrum of neurological abnormalities associated with Leber's hereditary
      optic neuropathy (LHON) and to determine the perceptual consequences of auditory
      neuropathy (AN) in affected listeners. Forty-eight subjects confirmed by genetic
      testing as having one of four mitochondrial mutations associated with LHON
      (mt11778, mtDNA14484, mtDNA14482 and mtDNA3460) participated. Thirty-two of these
      had lost vision, and 16 were asymptomatic at the point of data collection. While
      the majority of individuals showed normal sound detection, >25% (of both
      symptomatic and asymptomatic participants) showed electrophysiological evidence
      of AN with either absent or severely delayed auditory brainstem potentials.
      Abnormalities were observed for each of the mutations, but subjects with the
      mtDNA11778 type were the most affected. Auditory perception was also abnormal in
      both symptomatic and asymptomatic subjects, with >20% of cases showing impaired
      detection of auditory temporal (timing) cues and >30% showing abnormal speech
      perception both in quiet and in the presence of background noise. The findings of
      this study indicate that a relatively high proportion of individuals with the
      LHON genetic profile may suffer functional hearing difficulties due to neural
      abnormality in the central auditory pathways.

PMID- 21887512
TI  - A case of segmental zoster paresis with enhanced anterior and posterior spinal
      roots on MRI.

PMID- 21887511
TI  - Predictive value of neurological examination for early cortical responses to
      somatosensory evoked potentials in patients with postanoxic coma.
AB  - Bilateral absence of cortical N20 responses of median nerve somatosensory evoked
      potentials (SEP) predicts poor neurological outcome in postanoxic coma after
      cardiopulmonary resuscitation (CPR). Although SEP is easy to perform and
      available in most hospitals, it is worthwhile to know how neurological signs are
      associated with SEP results. The aim of this study was to investigate whether
      specific clinical neurological signs are associated with either an absent or a
      present median nerve SEP in patients after CPR. Data from the previously
      published multicenter prospective cohort study PROPAC (prognosis in postanoxic
      coma, 2000-2003) were used. Neurological examination, consisting of Glasgow Coma
      Score (GCS) and brain stem reflexes, and SEP were performed 24, 48, and 72 h
      after CPR. Positive predictive values for predicting absent and present SEP, as
      well as diagnostic accuracy were calculated. Data of 407 patients were included.
      Of the 781 SEPs performed, N20 s were present in 401, bilaterally absent in 299,
      and 81 SEPs were technically undeterminable. The highest positive predictive
      values (0.63-0.91) for an absent SEP were found for absent pupillary light
      responses. The highest positive predictive values (0.71-0.83) for a present SEP
      were found for motor scores of withdrawal to painful stimuli or better.
      Multivariate analyses showed a fair diagnostic accuracy (0.78) for neurological
      examination in predicting an absent or present SEP at 48 or 72 h after CPR. This
      study shows that neurological examination cannot reliably predict absent or
      present cortical N20 responses in median nerve SEPs in patients after CPR.

PMID- 21887513
TI  - Leonid Ivanovich Omorokov (1881-1971).

PMID- 21887514
TI  - Avicenna (980-1037 AD).

PMID- 21887515
TI  - Rituximab responsive multiple radiculopathies and cranial nerve palsies in
      association with chronic lymphocytic leukaemia.

PMID- 21887516
TI  - RGMA and neogenin protein expression are influenced by lens injury following
      optic nerve crush in the rat retina.
AB  - BACKGROUND: The death and the failure of neurons to regenerate their axons after
      lesion of the central nervous system in mammals, as in the case of spinal cord
      injury and optic nerve trauma, remain a challenge. In this study, we focused on
      the repulsive guidance molecule A (RGMA) and its receptor neogenin. Since it was
      reported that RGMA+ cells accumulate in lesioned areas after spinal cord injury,
      brain trauma, and optic nerve crush, and curiously, anti-apoptotic effects of
      RGMA were also described, we investigated the role of RGMA and neogenin in the
      retina after optic nerve crush (ONC). METHODS: We evaluated the spatial and
      temporal protein pattern of RGMA and neogenin in the rat retina without (non
      regenerating model) or with (regenerating model) lens injury (LI). We
      investigated the presence of RGMA, neogenin and other proteins at up to nine time
      points (6 h-20 days post-surgery) by performing immunohistochemistry and Western
      blots. RESULTS: Independent of the treatment, RGMA protein was present in the
      nuclear layers (NLs), plexiform layers (PLs), nerve fiber layer (NFL), and in
      retinal ganglion cells (RGCs) of the rat retina. RGC and nerve fibers were always
      RGMA+. Further RGMA+ cells in the retina were blood vessel endothelial cells,
      astrocytes, Muller cells, and some microglial cells. The RGMA pattern for the
      specific retinal cells resembled those of previously published data. The neogenin
      pattern was congruent to the RGMA pattern. Western blots of retinal tissue showed
      further RGMA+ products only in LI animals. Furthermore, a higher amount of RGMA
      was found in the retinae of ONC + LI rats compared to ONC rats. CONCLUSIONS:
      Although a difference in the localization of RGMA is not obvious, the difference
      in the amount of RGMA is striking, the higher amount of RGMA in the retinae of
      ONC + LI rats compared to ONC rats indicates a role for RGMA during
      degeneration/regeneration processes. Our results are consistent with several
      reported neuroprotective effects of RGMA. Our new data showing the upregulation
      of RGMA after ONC in our regenerating model (plus LI) confirm these findings
      conducted in different settings.

PMID- 21887517
TI  - Immunomodulative efficacy of bone marrow-derived mesenchymal stem cells cultured
      in human platelet lysate.
AB  - Human mesenchymal stem cells (hMSCs) are considered to be a promising tool for
      novel cell-based therapies. Clinical applications in solid organ transplantation
      were hampered by the dependence on animal serum for hMSCs clinical scale
      expansion until substitution with human platelet lysate (HPL) became a promising
      alternative. Therefore we focused on a direct comparison of immunomodulatory
      properties of hMSCs cultured in HPL or fetal calf serum (FCS). Phenotypic
      characterization, detection of cytokine secretion and effects on alloantigen- and
      mitogen-induced lymphocyte proliferation as well as degranulation of
      cytomegalovirus-specific cytotoxic T cells were applied in potency assays. We
      demonstrated that HPL-cultured MSCs have comparable immunomodulatory capacities
      to their FCS-cultured counterparts. The observed immunomodulatory properties
      include a beneficial inhibitory effect on immune cell proliferation and an
      unaffected viral T cell immunity. Thus, culturing hMSCs in HPL generates an
      efficient and safe expansion combined with intriguing immunomodulatory properties
      making these cells an attractive cell therapeutic tool.

PMID- 21887518
TI  - Altered proportions of naive, central memory and terminally differentiated
      central memory subsets among CD4+ and CD8 + T cells expressing CD26 in patients
      with type 1 diabetes.
AB  - Type 1 diabetes is an autoimmune process predominantly T-cell mediated. CD26
      plays a role in T-cell costimulation, migration, memory development, thymic
      maturation and emigration patterns. In peripheral blood from 55 patients with
      type 1 diabetes and 20 healthy controls, CD4(+) and CD8(+) T cells expressing
      CD26 were differentiated into naive (N, CD45RA(+)CCR7(+)), central memory (CM,
      CD45RA(-)CCR7(+)), effector memory (EM, CD45RA(-)CCR7(-)), and terminally
      differentiated effector memory (TEMRA, CD45RA(+)CCR7(-)). In type 1 diabetes,
      CD4(+) and CD8(+) T cells expressing CD26 showed a distinctive differentiation
      profile: percentages and absolute numbers of CM and N cells were reduced, whereas
      those of TEMRA cells were markedly increased. The indices of intermediate- and
      long-term glycaemic control were associated negatively with the number of CM and
      N cells while positively with the number of TEMRA cells. The considerable
      accumulation of TEMRA T cells in our patients suggests life-long stimulation by
      protracted antigen exposure (viruses, other agents or residual self-antigens?) or
      a homeostatic defect in the regulation/contraction of immune responses.

PMID- 21887519
TI  - High contribution of SAR11 to microbial activity in the north west Mediterranean
      Sea.
AB  - We investigated the abundance and activity of SAR11 on a monthly time scale
      between January 2008 and October 2008 in the oligotrophic NW Mediterranean Sea.
      Applying MICRO-CARD-FISH, we observed that SAR11 had a large contribution to bulk
      abundance (37 +/- 6% of DAPI-stained cells) and to bulk bacterial heterotrophic
      production (BHP), as estimated from leucine incorporation (55 +/- 15% of DAPI
      cells assimilating leucine) in surface waters (5 m) throughout the study period.
      SAR11 contributed also substantially to the assimilation of glucose, ATP, and a
      combination of amino acids (44 +/- 17%, 37 +/- 14%, and 43 +/- 12% of DAPI cells
      assimilating these compounds, respectively), organic compounds that provide
      either single or combined sources of C, P, and N. Temporal changes in the
      abundance of SAR11 cells that assimilated leucine, glucose, amino acids, and ATP
      revealed a pattern consistent with that of substrate-active DAPI cells,
      suggesting that the activity of SAR11 can explain to a large extent the
      variability in total cells contributing to the utilization of these compounds.
      Short-term nutrient enrichment experiments performed on each sampling date
      revealed a strong co-limitation of at least two of the three elements analyzed
      (C, N, P), in particular, during summer and early autumn. The in situ abundance
      of SAR11 cells assimilating leucine appeared to increase with P limitation as
      determined in the nutrient enrichment experiments (r = 0.81, p = 0.015). Our
      results demonstrate that SAR11 is an important component of the active bacterial
      community in the NW Mediterranean Sea. Our observations further indicate that the
      activity of the bulk bacterial community is linked to the activity of SAR11,
      possibly due to its adaptation to nutrient limitation.

PMID- 21887520
TI  - Association of Toll-like receptor 2 polymorphisms with National Institute of
      Health Stroke Scale scores of ischemic stroke patients.
AB  - Toll-like receptor 2 (TLR2) has been shown to have an important role in the
      postischemic inflammatory response and to contribute to ischemic brain damage. In
      this study, we investigated whether coding region single nucleotide polymorphisms
      (SNPs) of the TLR2 gene were associated with ischemic stroke (IS) and with
      clinical phenotypes in IS patients. We genotyped two SNPs (rs3804099 [Asn199Asn]
      and rs3804100 [Ser450Ser]) using direct sequencing in 202 IS patients and 291
      control subjects. No SNPs of the TLR2 gene were found to be associated with IS.
      However, in analysis of clinical phenotypes, we found that rs3804099 was
      associated with the National Institute of Health Stroke Scale (NIHSS) scores of
      IS patients in codominant (TC vs. TT, p = 0.0005; CC vs. TT, p = 0.0007) and
      dominant models (TC/CC vs. TT, p = 0.0001). Also, rs3804100 revealed significant
      association in codominant (TC vs. TT, p = 0.0002; CC vs. TT, p = 0.008) and
      dominant models (TC/CC vs. TT, p < 0.0001). In allele frequency analysis, we also
      found that the C alleles of rs3804099 and rs3804100 were associated with higher
      NIHSS scores (p = 0.0003 in rs3804099; p = 0.0001 in rs3804100). Our results
      suggest that TLR2 may be related to severe IS.

PMID- 21887521
TI  - Extrapyramidal syndromes in frontotemporal degeneration.
AB  - Descriptions of extrapyramidal (EP) involvement in Pick's disease (renamed
      recently as FTD) appeared 80 years ago. CBD pathology was confirmed as a common
      substrate for primary progressive aphasia (PPA). We suggested that CBD and PPA
      should be included with frontal lobe dementia as Pick complex. PSP was prototype
      for "subcortical dementia", and aphasia and apraxia, considered unusual for PSP,
      are now seen as a rule. The overlap of PSP and CBD is considerable. We recently
      reviewed our cohort with EPS in FTD and identified 22 patients with the movement
      disorder as a first syndrome and another larger group of 48 patients who
      developed EPS after an initial onset with a cognitive disorder: aphasic,
      behavioral or both. All cognitive onset CBD/PSP patients and all but two with
      motor onset developed aphasia during the course of their illness. General
      cognitive and behavioral measures are similar for each presentation, but language
      scores are worse in cognitive onset cases, reflecting the frequency of aphasic
      presentations. Anomic patients become non-fluent, logopenic, agrammatic and mute.
      Using the Frontal Behavioral Inventory (FBI), a questionnaire specifically
      designed for the spectrum of apathy and disinhibition displayed by patients with
      FTD, we have documented the behavior change in CBD/PSP with motor and cognitive
      onsets. The significant personality changes consisted of apathy, disinhibition,
      perseveration and inattention, some of the core symptoms of FTD. In 18 autopsied
      cases, 15 had tau pathology. The overlap of CBD/PSP with PPA and bvFTD suggests a
      spectrum of related entities and predicts tau-positive pathology. Cross-sectional
      studies without significant follow-up may not observe the subsequent development
      language or behavior deficit, or the evolution from PPA and/or FTD-bv to CBD/PSP.

PMID- 21887522
TI  - Assessment of genetic stability and instability of tissue culture-propagated
      plantlets of Aloe vera L. by RAPD and ISSR markers.
AB  - Efficient plantlet regeneration with and without intermediate callus phase was
      achieved for a selected genotype of Aloe vera L. which is sweet in test and used
      as a vegetable and source of food. Random amplified polymorphic DNA (RAPD) and
      inter simple sequence repeats (ISSR) marker assays were employed to evaluate
      genetic stability of plantlets and validate the most reliable method for true-to
      type propagation of sweet aloe, among two regeneration systems developed so far.
      Despite phenotypic similarities in plantlets produced through both regeneration
      systems, the differences in genomic constituents of plantlets produced through
      intermediate callus phase using soft base of inflorescence have been effectively
      distinguished by RAPD and ISSR markers. No polymorphism was observed in
      regenerants produced following direct regeneration of axillary buds, whereas 80%
      and 73.3% of polymorphism were observed in RAPD and ISSR, respectively, in the
      regenerants produced indirectly from base of the inflorescence axis via an
      intermediate callus phase. Overall, 86.6% of variations were observed in the
      plantlets produced via an intermediate callus phase. The occurrence of genetic
      polymorphism is associated with choice of explants and method used for plantlet
      regeneration. This confirms that clonal propagation of sweet aloe using axillary
      shoot buds can be used for commercial exploitation of the selected genotype where
      a high degree of fidelity is an essential prerequisite. On the other hand, a high
      degree of variations were observed in plantlets obtained through indirect
      regeneration and thus cannot be used for the mass multiplication of the genotype;
      however, it can be used for crop improvement through induction of somaclonal
      variations and genetic manipulations.

PMID- 21887523
TI  - Immobilization of Pseudomonas stutzeri lipase for the transesterification of wood
      sterols with fatty acid esters.
AB  - Lipase from Pseudomonas stutzeri PL-836 was immobilized on hydrophobic supports
      and evaluated in the transesterification of wood sterols in solvent-free and
      solvent-containing media. Triton X-100 was used as additive during immobilization
      in butyl and octadecyl sepabeads increasing enzyme activity yield by 5% and 60%,
      respectively. Hyperactivation was observed during immobilization in EC octadecyl
      sepabeads with enzyme activity yield of 200% and protein immobilization yield of
      93%. Thermostability of the immobilized enzyme was assessed at 50  degrees C in
      different media in the absence and presence of exogenous solvents. The presence
      of Triton X-100 during immobilization reduced enzyme stability while tert-butanol
      increased it. Transesterification in solvent-free and solvent-containing medium
      with lipase immobilized in EC octadecyl sepabeads showed that the presence of
      exogenous solvent increased both conversion yield and productivity. At rather
      high levels of biocatalyst hydration (40% on wet basis) the presence of tert
      butanol in the reaction medium more than doubled conversion yield and
      productivity.

PMID- 21887524
TI  - What is the ideal blood pressure goal for patients with stage III or higher
      chronic kidney disease?
AB  - Hypertension and chronic kidney disease (CKD) are public health problems well
      known to the national and international medical communities. Blood pressure (BP)
      control in patients with CKD stage III and IV plays a key factor in reducing
      cardiovascular risk and renal disease progression. We conducted a literature
      review of recent studies addressing BP targets and cardiorenal outcomes in
      patients with CKD. Multiple studies demonstrated cardiovascular benefits
      associated with greater BP reduction. Nevertheless, a U-shaped relationship
      between BP, cardiovascular events, and renal function was present. In patients
      with CKD stage III and IV, a BP less than 140/90 mm Hg appeared to be a
      reasonable target. Moreover, in patients with CKD and proteinuria of more than 1
      g/day, a target systolic BP of 120 to 130 mm Hg and diastolic BP of 70 to 80 mm
      Hg yielded the greatest benefit while avoiding most of the adverse cardiovascular
      outcomes associated with lower levels of BP.

PMID- 21887525
TI  - Identification of fruit volatiles from green hawthorn (Crataegus viridis) and
      blueberry hawthorn (Crataegus brachyacantha) host plants attractive to different
      phenotypes of Rhagoletis pomonella flies in the southern United States.
AB  - The apple maggot fly, Rhagoletis pomonella, infests several hawthorn species in
      the southern USA. In a companion paper, we showed that R. pomonella flies
      infesting two different mayhaw species (Crataegus opaca and C. aestivalis) can
      discriminate between volatile blends developed for each host fruit, and that
      these blends are different from previously constructed blends for northern fly
      populations that infest domestic apple (Malus domestica), downy hawthorn
      (Crataegus mollis), and flowering dogwood (Cornus florida). Here, we show by
      using coupled gas chromatography and electroantennographic detection (GC-EAD),
      gas chromatography with mass spectrometry (GC-MS), and flight tunnel bioassays,
      that two additional southern hawthorn fly populations infesting C. viridis (green
      hawthorn) and C. brachyacantha (blueberry hawthorn) also can discriminate between
      volatile blends for each host fruit type. A 9-component blend was developed for
      C. viridis (3-methylbutan-1-ol [5%], butyl butanoate [19.5%], propyl hexanoate
      [1.5%], butyl hexanoate [24%], hexyl butanoate [24%], pentyl hexanoate [2.5%], 1
      octen-3-ol [0.5%], pentyl butanoate [2.5%], and (3E)-4,8-dimethyl-1,3,7
      nonatriene (DMNT) [20.5%]) and an 8-component blend for C. brachyacantha (3
      methylbutan-1-ol [0.6%], butyl acetate [50%], pentyl acetate [3.5%], butyl
      butanoate [9%], butyl hexanoate [16.8%], hexyl butanoate [16.8%], 1-octen-3-ol
      [0.3%], and pentyl butanoate [3%]). Crataegus viridis and C. brachyacantha-origin
      flies showed significantly higher levels of upwind oriented flight to their natal
      blend in flight tunnel assays compared to the alternate, non-natal blend and
      previously developed northern host plant blends. The presence of DMNT in C.
      viridis and butyl acetate in C. brachyacantha appeared to be largely responsible
      for driving the differential response. This sharp behavioral distinction
      underscores the diversity of odor response phenotypes in the southern USA, points
      to possible host race formation in these populations, and despite the presence of
      several apple volatiles in both blends, argues against a functional apple race
      existing on southern host plants prior to the introduction of apple to North
      America.

PMID- 21887527
TI  - Excess mortality from seasonal influenza is negligible below the age of 50 in
      Israel: implications for vaccine policy.
AB  - PURPOSE: Evaluation of the severity of pandemic influenza requires reliable
      estimates of mortality attributable to the seasonal influenza. METHODS: Excess
      age-specific mortality during periods of influenza activity was evaluated in
      Israel during the period 1999-2006 for three death categories. For each
      respiratory year, the lowest monthly moving average for the mortality rate was
      subtracted from each month in the period of influenza activity. Average mortality
      rates in years with minimal influenza activity were deducted from corresponding
      months to exclude winter mortality unrelated to influenza. The sums of these
      results were used as estimates of excess mortality rates. RESULTS: Overall excess
      mortality rates ranged from 7.7 to 36.1 per 100,000 for all causes, and from 4.4
      to 24.4 per 100,000 for respiratory and circulatory causes. Influenza was
      associated with an average of 869 (range 280-1,516) deaths annually from
      respiratory and circulatory diseases during seasons with significant influenza
      activity. About 90% of the influenza-associated mortality from respiratory and
      circulatory diseases was in the age group 65+ years and about 1% in the age group
      <50 years. The age group <50 years accounted for an annual average of seven
      deaths from respiratory and circulatory diseases. CONCLUSION: Annual mortality
      associated with seasonal influenza is highly variable. Under the age of 50 years,
      there is minimal seasonal influenza associated mortality. This information
      provides an important baseline for evaluating the severity of the A(H1N1) 2009
      influenza pandemic, where persons under 50 years of age were often
      disproportionately represented.

PMID- 21887526
TI  - Clinical characteristics and outcomes of bacteremia due to different genomic
      species of Acinetobacter baumannii complex in patients with solid tumors.
AB  - PURPOSE: Acinetobacter baumannii, Acinetobacter genomic species 3 (AGS 3), and
      Acinetobacter genomic species sensu Tjernberg and Ursing (AGS 13TU) are
      phenotypically indistinguishable and are often reported together as the A.
      baumannii complex (ABC). Few studies have investigated the difference in outcome
      caused by these different species, and all involved heterogeneous groups of
      patients. This study aimed to delineate whether there are differences in the
      clinical characteristics and outcome among patients with solid tumors and
      bacteremia caused by A. baumannii or two other non-baumannii ABC species (AGS 3
      plus AGS 13TU). METHODS: Patients with solid tumors and ABC bacteremia over a
      period of 5 years in a medical center were identified. The patient data were
      retrospectively reviewed and analyzed. RESULTS: We identified 103 patients with
      ABC bacteremia during the study period. Bacteremia was due to A. baumannii in 30
      patients, AGS 3 in 24 patients, and AGS 13TU in 49 patients. Among the 103
      patients with ABC bacteremia, recent stay in the intensive care unit (ICU) (p =
      0.008) was independently associated with the acquisition of A. baumannii
      bacteremia. Multivariate analysis revealed that bacteremia caused by A. baumannii
      (hazard ratio [HR] 2.990, 95% confidence interval [CI], 1.021-8.752, p = 0.046)
      and Acute Physiology and Chronic Health Evaluation (APACHE) II score >=21 (HR
      4.623, 95% CI 1.348-15.859, p = 0.015) were independent factors associated with
      14-day mortality. CONCLUSIONS: Infection with A. baumannii and a high APACHE II
      score (>=21) might be associated with poor outcome in patients with solid tumors
      and ABC bacteremia.

PMID- 21887528
TI  - Penetrating aortic ulcer: defining risks and therapeutic strategies.
AB  - In addition to classic aortic dissection and intramural hematoma, acute aortic
      syndrome also includes penetrating aortic ulcers (PAU). The recent advent of
      highly detailed axial imaging allows closer assessment of PAU and its
      pathophysiology. However, there is still ongoing discussion about the natural
      history of the disease, leading to challenging questions concerning the optimal
      treatment strategy, particularly in asymptomatic patients. In this review,
      current indications for treatment, with an emphasis on PAU repair in the
      endovascular era, are discussed.

PMID- 21887529
TI  - [German Registry for Acute Aortic Dissection Type A (GERAADA): initial results].
AB  - BACKGROUND: The working group "Aortic Surgery and Interventional Vascular
      Surgery" of the German Society for Thoracic and Cardiovascular Surgery (GSTCVS)
      set up the German registry for acute aortic dissection type A (GERAADA) in July
      2006. This web-based database was developed to record data of patients who had
      undergone surgery for aortic dissection type A (AADA). The aim of GERAADA is to
      learn from analyzing the data of AADA patients how to improve the perioperative
      management and surgical treatment of patients with AADA and to identify possible
      parameters affecting patient risk and outcome. PATIENTS AND METHODS: Between July
      2006 and June 2009 (2010), 1558 (2137) patients with AADA were enrolled in the
      multi-center, prospective GERAADA database by 50 cardiac surgery centers in
      German-speaking countries in Europe. Data on patients' preoperative and
      intraoperative status, postoperative complications, midterm results and
      circumstances of death were recorded. Data were analyzed to identify risk factors
      influencing the outcome of these patients. The Institute of Medical
      Biostatistics, Epidemiology and Informatics (IMBEI) in Mainz performed the
      statistical analyses. RESULTS: Analyses from GERAADA reveal a thirty-day
      mortality of 17% in 2137 AADA patients. Only short interventions in aortic arch
      surgery are safe during hypothermic circulatory arrest even without selective
      cerebral perfusion. If circulatory arrest times of over 30 min. are anticipated,
      antegrade cerebral perfusion is strongly recommended during the entire arch
      intervention using cardiopulmonary bypass. Surgical strategy in terms of isolated
      ascending aortic replacement versus ascending aortic replacement combined with
      aortic arch repair had no statistical relevant influence on 30-day mortality.
      AADA surgical results in elderly patients are more encouraging than those treated
      without surgery. Surgery is even feasible in octogenarians with a 35% mortality
      rate. CONCLUSION: The aim of this registry is to optimize AADA patients' medical
      care, thereby reducing their morbidity and mortality. AADA treatment should
      always involve open surgery. Initial analyses from GERAADA provide clinically
      relevant insights concerning patients with AADA, and may enable therapeutic
      recommendations for improving perioperative and surgical management. Our latest
      study detected significant influencing risk factors for the outcome of AADA
      patients and may contribute to a consensus in setting guidelines for standard
      medical treatment. PERSPECTIVE: A European Registry of Aortic Diseases ("EuRADa")
      is being established this year under the leadership of the "Vascular Domain" of
      the European Association for Cardio-Thoracic Surgery (EACTS). This database will
      collect parameters on all aortic diseases, dissection types A and B, aneurysms,
      perforating ulcer (PAU), intramural wall hematoma (IMH), traumatic aortic
      ruptures, and all potential treatment strategies (medical treatment, open
      surgical and endovascular).

PMID- 21887530
TI  - Aortic intramural hematoma: aspects of pathogenesis 2011.
AB  - Non-invasive tomographic imaging modalities have recently contributed to
      identifying aortic intramural hematoma, a variant form of classic dissection,
      which is characterized by the absence of an intimal tear and thus the absence of
      direct flow communication, and which represents an important disease entity in
      acute aortic syndrome. Clinical investigations have revealed that intramural
      hematoma has characteristic clinical features and that the natural remodeling
      process of hematoma is different from that of classic aortic dissection. These
      findings suggest that intramural hematoma is not just a precursor to aortic
      dissection, but may be a unique disease entity with a more favorable prognosis
      compared to aortic dissection. There is regional heterogeneity regarding the
      relative incidence of this hematoma, with higher incidence seen in Eastern
      countries. Due to favorable outcomes with medical treatment in Asian patients
      with type A intramural hematoma, a tailored or individualized approach based on
      risk stratification using initial clinical information and including imaging
      studies and timely surgical repair has been suggested in hemodynamically stable
      patients; however, these results need to be confirmed in other patient
      populations. The concept of a "micro-tear" which cannot be easily visualized
      using conventional imaging modalities has been raised: "echo-free space" on
      transesophageal echocardiography and "focal contrast enhancement" on ultra-fast
      computerized tomography have drawn many physicians' attention, and the
      possibility of a pathophysiologic link between classic aortic dissection and
      intramural hematoma has been discussed. Further investigations are needed to test
      whether intramural hematoma begins with an initial intimal tear and a different
      aortic status--characterized by a more rigid and non-compliant aorta associated
      with old age or long-standing hypertension--and results in an apparently absent
      intimal flap.

PMID- 21887531
TI  - TEVAR: the solution to all aortic problems?
AB  - Chronic as well as acute diseases of the thoracic aorta are attracting increasing
      attention, both in the light of an ageing Western and Oriental population and
      with the proliferation of modern diagnostic imaging modalities. While classic
      surgical strategies still dominate the treatment of pathology of the ascending
      aorta and the proximal arch region, new endovascular concepts are emerging and
      are likely to evolve as primary treatment strategies for descending and abdominal
      aortic pathology. Additionally, aortic arch pathologies are becoming the target
      of hybrid approaches combining surgical head-vessel debranching and
      interventional stent-graft implantation in an attempt to improve outcome by
      avoiding the high risk of open arch repair or complete replacement. Nonetheless,
      due to the complexity of the underlying vascular disease, each patient should be
      discussed in a team consisting of cardiologists, cardiac surgeons, and an imaging
      specialist in order to design an individualized therapeutic strategy carried out
      best in a center with experience in both endovascular and surgical procedures.

PMID- 21887532
TI  - High diagnostic accuracy of low-dose gated-SPECT with solid-state ultrafast
      detectors: preliminary clinical results.
AB  - PURPOSE: Appropriate use of SPECT imaging is regulated by evidence-based
      guidelines and appropriateness criteria in an effort to limit the burden of
      radiation administered to patients. We aimed at establishing whether the use of a
      low dose for stress-rest single-day nuclear myocardial perfusion imaging on an
      ultrafast (UF) cardiac gamma camera using cadmium-zinc-telluride solid-state
      detectors could be used routinely with the same accuracy obtained with standard
      doses and conventional cameras. METHODS: To this purpose, 137 consecutive
      patients (mean age 61 +/- 8 years) with known or suspected coronary artery
      disease (CAD) were enrolled. They underwent single-day low-dose stress-rest
      myocardial perfusion imaging using UF SPECT and invasive coronary angiography.
      Patients underwent the first scan with a 7-min acquisition time 10 min after the
      end of the stress protocol (dose range 185 to 222 MBq of (99m)Tc-tetrofosmin).
      The rest scan (dose range 370 to 444 MBq of (99m)Tc-tetrofosmin) was acquired
      with a 6-min acquisition time. The mean summed stress scores (SSS) and mean
      summed rest scores (SRS) were obtained semiquantitatively. RESULTS: Coronary
      angiograms showed significant epicardial CAD in 83% of patients. Mean SSS and SRS
      were 10 +/- 5 and 3 +/- 3, respectively. Overall the area under the ROC curve for
      the SSS values was 0.904, while the areas under the ROC curves for each vascular
      territory were 0.982 for the left anterior descending artery, 0.931 for the left
      circumflex artery and 0.889 for the right coronary artery. CONCLUSION: This pilot
      study demonstrated the feasibility of a low-dose single-day stress-rest fasting
      protocol performed using UF SPECT, with good sensitivity and specificity in
      detecting CAD at low patient exposure, opening new perspectives in the use of
      myocardial perfusion in ischaemic patients.

PMID- 21887533
TI  - Delayed presentation of splenic rupture following colonoscopy: clinical and CT
      findings.
AB  - The purpose of this study is to investigate the clinical and CT findings in
      patients with symptomatic colonoscopy-induced splenic rupture, and to assess for
      common features among this cohort. Multi-center search yielded 11 adults with
      symptomatic splenic injury related to colonoscopy. Workup included abdominal CT
      in 10 (91%) cases and abdominal radiography in two patients (one patient had
      both). Colonoscopy findings, post-procedural course, and CT findings were
      systematically reviewed. Mean patient age was 62.2 years (range, 51-84 years); 8
      (73%) of 11 were female. The majority (64%) of colonoscopies were for screening.
      No immediate complications were reported at optical colonoscopy;
      tortuosity/redundancy was noted in five cases. Except for a small (8 mm) polyp in
      one case and a large (10 mm) polyp in another, the remaining nine patients had
      either diminutive or no polyps. Only one patient presented with hemodynamic
      instability during post-colonoscopy recovery; the other ten had a delayed
      presentation ranging from 8 h to 8 days (mean, 2.1 days). All 11 patients
      presented with abdominal pain. CT was diagnostic for splenic injury with
      subcaspular and/or perisplenic hematoma in all ten CT cases. Hemoperitoneum was
      present in eight, visible splenic laceration in three cases, and splenic artery
      pseudoaneurysm in one case. Five patients underwent splenectomy (four emergent)
      and six patients were treated conservatively. Average hospital stay was 5.5 days
      (range, 3-10 days). Colonoscopy-induced splenic rupture characteristically
      presents as a delayed and often serious complication. In cases of apparent non
      traumatic splenic hematoma or rupture at CT, eliciting a history of recent
      colonoscopy may identify the etiology.

PMID- 21887534
TI  - Immunohistochemical staining of human sperm cells in smears from sexual assault
      cases.
AB  - In the routine clinical examination of sexual assault victims, apart from
      documenting physical evidence of abuse, securing evidence, typically DNA from
      blood, semen, or saliva, is an important part of the process. Often the presence
      of semen is considered a most interesting piece of evidence. Not only does it
      often contain enough DNA for DNA profiling, but it also strongly indicates that
      an actual sexual act has taken place. The examination of smear slides obtained in
      sexual assault cases is a time-consuming task especially for the less trained and
      in cases where the smear only contains few sperm cells. In this work the goal was
      to develop a procedure to rapidly visualize human sperm cells in smear slides
      with the use of bright-field microscopy. Using SPERM HY-LITERTM by Independent
      Forensics, human sperm cells are visualized using a fluorescently labeled mouse
      antibody which significantly decreases the time used to screen smears. By further
      using an EnVision+ (DAKO) protocol, it was possible to create an
      immunohistochemical staining method to visualize sperm cells in bright-field
      microscopy with the same level of certainty as when using SPERM HY-LITERTM.

PMID- 21887535
TI  - Analysis of 12 X-STRs in Greenlanders, Danes and Somalis using Argus X-12.
AB  - X-chromosome markers have become a useful set of markers of choice when certain
      complex kinship cases need to be unravelled. The Argus X-12 kit allows the co
      amplification in a single PCR reaction of 12 X-chromosome short tandem repeats
      located in four linkage groups. A number of 507 unrelated individuals from
      Greenland, Denmark and Somalia together with two generation families were typed
      using the Argus X-12 kit. Silent alleles for the DXS10148 and DXS10146 systems
      were observed in males, mostly from Somalia. High levels of intrapopulation
      variability and therefore high forensic parameter values were calculated for the
      three studied populations. The population in Greenland showed a significantly
      lower intrapopulation variability and a high genetic differentiation compared
      with 13 other populations. Significant levels of linkage disequilibrium were
      observed between markers belonging to the same linkage group, mainly in the
      populations in Greenland and Somalia. Family studies allowed the calculation of
      mutation and recombination frequencies. A higher male versus female mutation rate
      was obtained, with an average value of 3.3 * 10(-3). Recombination fraction
      calculations performed on two generation families showed, as previously
      described, a not complete independence between X-chromosome linkage groups 3 and
      4.

PMID- 21887536
TI  - Automated striatal uptake analysis of 18F-FDOPA PET images applied to Parkinson's
      disease patients.
AB  - OBJECTIVE: 6-[(18)F]Fluoro-L: -DOPA (FDOPA) is a radiopharmaceutical valuable for
      assessing the presynaptic dopaminergic function when used with positron emission
      tomography (PET). More specifically, the striatal-to-occipital ratio (SOR) of
      FDOPA uptake images has been extensively used as a quantitative parameter in
      these PET studies. Our aim was to develop an easy, automated method capable of
      performing objective analysis of SOR in FDOPA PET images of Parkinson's disease
      (PD) patients. METHODS: Brain images from FDOPA PET studies of 21 patients with
      PD and 6 healthy subjects were included in our automated striatal analyses.
      Images of each individual were spatially normalized into an FDOPA template.
      Subsequently, the image slice with the highest level of basal ganglia activity
      was chosen among the series of normalized images. Also, the immediate preceding
      and following slices of the chosen image were then selected. Finally, the
      summation of these three images was used to quantify and calculate the SOR
      values. The results obtained by automated analysis were compared with manual
      analysis by a trained and experienced image processing technologist. RESULTS: The
      SOR values obtained from the automated analysis had a good agreement and high
      correlation with manual analysis. The differences in caudate, putamen, and
      striatum were -0.023, -0.029, and -0.025, respectively; correlation coefficients
      0.961, 0.957, and 0.972, respectively. CONCLUSIONS: We have successfully
      developed a method for automated striatal uptake analysis of FDOPA PET images.
      There was no significant difference between the SOR values obtained from this
      method and using manual analysis. Yet it is an unbiased time-saving and cost
      effective program and easy to implement on a personal computer.

PMID- 21887538
TI  - [Biodegradable screw versus a press-fit bone plug fixation for ACL
      reconstruction: a prospective randomized study].
AB  - BACKGROUND: Press-fit fixation of a tendon graft has been advocated in order to
      achieve tendon to bone healing. HYPOTHESIS: Fixation of a tendon graft with a
      porous bone scaffold limits bone tunnel enlargement compared with a biodegradable
      interference screw fixation. METHODS: Between 2005 and 2006, 20 patients (17 men,
      3 women) were enrolled in this study for primary reconstruction of the ACL.
      Patients were randomized to either obtain graft fixation in the tibial tunnel by
      means of an interference screw (I) or a press-fit fixation with a porous bone
      cylinder (P). Three months after surgery, a CT scan of the knee was performed and
      tunnel enlargement was analysed in the coronal and sagittal planes for the
      proximal, middle and distal thirds of the tunnel. After 6 months, 1 and 2 years,
      International Knee Documentation Committee (IKDC), Tegner and Lysholm scores of
      both groups were compared. RESULTS: The bone tunnel enlargement was 106.9+/-10.9%
      for group P and 121.9+/-9.0% for group I (P<0.02) in the AP plane and 102.8+/
      15.2% vs 121.5+/-10.1% in the coronal plane (P<0.01). IKDC, Tegner, and Lysholm
      scores improved in both groups from pre- to postoperative assessment without
      significant differences between the two groups. There was a trend to higher knee
      stability in group P after 3 months (0.6+/-1.4 mm vs 1.81+/-.5 mm, P=0.08).
      CONCLUSIONS: Both interference screw and a press-fit fixation lead to a high
      number of good or very good outcomes after ACL reconstruction. Tibial press-fit
      fixation decreases the amount of proximal bone tunnel enlargement. Press-fit
      fixation decreases the amount of proximal bone tunnel enlargement and improves
      bone to tendon contact.

PMID- 21887537
TI  - Interleukin-6 receptor enhances early colonization of the murine omentum by
      upregulation of a mannose family receptor, LY75, in ovarian tumor cells.
AB  - One of the earliest metastatic events in human ovarian cancer, tumor spread to
      the omentum, may be influenced by expression of interleukin 6 (IL6) and its
      cognate receptor (IL6Ralpha). Previous reports have shown that IL6 and IL6Ralpha
      expression is elevated in the serum and ascites of patients with ovarian cancer
      and that this can influence in vitro processes such as cell survival,
      proliferation and migration. In this study, overexpression of IL6Ralpha, and to a
      lesser extent IL6, enhanced tumor growth on the omentum. Moreover, adherence to
      plastic and to peritoneal extracellular matrix components was enhanced in tumor
      cells overexpressing IL6 or IL6Ralpha. Host production of IL6 and IL6Ralpha was
      also sufficient to influence tumor adherence to the omentum. Expression of
      LY75/CD205/DEC205, a collagen-binding mannose family receptor, was directly
      influenced by IL6Ralpha expression. Blocking LY75 with antibody reduced the
      adherence of tumor cells overexpressing IL6Ralpha to matrices in vitro and to the
      omentum. The association between IL6Ralpha expression and LY75 expression has not
      been previously reported, and the promotion of cellular adherence is a novel role
      for LY75. These studies indicate that overexpression of LY75 may be an additional
      mechanism by which IL6 signaling influences the progression of ovarian cancer,
      and suggests that blocking LY75 could be a valuable clinical strategy for
      reducing the early metastasis of ovarian cancer.

PMID- 21887540
TI  - Holism and sexual function: the difference between sex and atoms.

PMID- 21887539
TI  - Epithelial marker expression does not rule out a diagnosis of Ewing's sarcoma
      family of tumours.
AB  - Epithelial marker expression has been reported in Ewing's sarcoma family of
      tumors (ESFT). However, cytokeratin (CK), epithelial membrane antigen (EMA), and
      carcino embryonic antigen (CEA) prevalence has not been assessed thoroughly in a
      large series of genetically confirmed ESFT. The aim of the present study is to
      confirm the presence of epithelial markers in a large group of ESFT tested
      genetically for any of their specific gene fusions and the differential diagnosis
      with other small round cell tumors. To establish the prevalence of epithelial
      markers, we then performed immunohistochemical studies with antibodies CK
      (AE1/AE3), CK8/18, CK34beta12, EMA, E-cadherin, and CEA on 415 genetically
      confirmed ESFT. Immunoreactivity to cytokeratin, EMA, and CEA was present in
      19.2%, 6.6%, and 20.8% of cases, respectively. There was no significant
      association between epithelial markers and histological subtypes, but the
      atypical variant of ESFT expressed these markers in a high proportion compared
      with the peripheral neuroectodermal tumors and the conventional variant. The
      present findings confirm that epithelial marker expression in ESFT, including EMA
      and CEA, does not rule out a diagnosis of ESFT, and the integration of clinical,
      radiological, histopathological, immunohistochemical, and molecular genetic
      findings should form the basis for the diagnosis of bone and soft tissue
      sarcomas, especially in tumors with atypical or unusual phenotype.

PMID- 21887541
TI  - Pudendal neuralgia following transobturator inside-out tape procedure (TVT-O)-
      case report and anatomical study.
AB  - Persistent pain after TVT-O procedure is a rare complication. Nerve injuries have
      been suspected as a cause of persistent pain. We present one case of atypical
      postoperative pain--pudendal neuralgia following TVT-O procedure--which persisted
      3 years after the primary procedure. The patient required surgical removal of the
      tape, which brought only partial relief. Complete relief from pain was afterwards
      achieved with repeated local applications of anesthetics with corticosteroids.
      The recurrent stress urinary incontinence was treated with retropubic TVT.
      Pudendal nerve irritation was also described after retropubic sling procedure,
      and the cadaveric dissection indicated the theoretic possibility of nerve injury
      during retropubic sling procedure. To explain the mechanism of nerve injury, we
      performed cadaveric dissections on a formalin-embalmed female body. We were able
      to demonstrate the contact of the needle with the pudendal nerve after aberrant
      passage of the inserter.

PMID- 21887543
TI  - "Like a rabbit from a hat!"--a case of a sacrocolpopexy mesh being taken out by a
      patient.
AB  - Sacrocolpopexy, be it laparoscopic or abdominal, is associated with a risk of
      mesh extrusion. We report an interesting case of mesh extrusion with subsequent
      removal of the mesh from the vagina by the patient. We take this opportunity to
      review the literature regarding incidence, predisposing factors and complications
      of sacrocolpopexy mesh extrusion with specific reference to this case.

PMID- 21887542
TI  - Anterior sacrospinous ligament fixation associated with paravaginal repair using
      the Pinnacle device: an anatomical study.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this paper is to study the
      reproducibility and anatomical risks of anterior sacrospinous ligament (SSL)
      fixation associated with paravaginal repair using the Pinnacle device (Boston
      Scientific). METHODS: Simplified bilateral anterior SSL fixation associated with
      paravaginal fixation through the arcus tendineus fascia pelvis (ATFP) was
      performed on five fresh cadavers using the Pinnacle device. Cadaver dissection
      was then performed by open pelvic surgery. RESULTS: Eight SSL and ten ATFP were
      available for analysis. SSL fixations were optimal in four cases, too superficial
      in three cases, and too high in one case. Mean distance between SSL fixation and
      ischial spine was 18.6 mm (range 10 to 30 mm). Mean distance between SSL fixation
      and pudendal nerve was 6.5 mm (range 0 to 15 mm). ATFP fixations were optimal in
      five cases, good in four cases, and too superficial in one case. In one case
      (10%), the middle arm of the prosthesis was in contact with the ureter and
      traction on that arm resulted in ureteral kinking. CONCLUSIONS: Anterior SSL
      fixation associated with paravaginal repair using the PinnacleTM device was not
      reproducible every time in this cadaver study. These results confirm the need for
      specific training before starting anterior SSL fixations.

PMID- 21887544
TI  - Guidelines and standardisation documents should be published anonymously.
AB  - In the interest of progress and in order to avoid conflict of interest,
      guidelines and standardisation documents should be published anonymously, and
      they should undergo a mandatory review process by peers every few years.

PMID- 21887545
TI  - Lumbosacral spondylodiscitis: an unusual complication of abdominal
      sacrocolpopexy.
AB  - Lumbosacral spondylodiscitis, an unusual complication of abdominal sacrocolpopexy
      using synthetic polypropylene mesh is reported. A young sexually active female
      with stage IV pelvic organ prolapse was managed with abdominal hysterectomy and
      sacrocolpopexy. Cervical dysplasia demanded hysterectomy and sacrocolpopexy was
      done to achieve good long-term results. Mesh exposure was noticed in the early
      post-operative period which initially responded to conservative management. Eight
      weeks later, the patient reported with severe pain in lower back restricting her
      physical movements and ambulation. Further evaluation with magnetic resonance
      imaging (MRI) confirmed lumbosacral spondylodiscitis, due to the infected mesh
      which warranted a complete removal of mesh by laparotomy. Removal of the mesh
      completely relieved her symptoms. Repeat MRI revealed resolving spondylodiscitis.
      The removal of mesh by itself was adequate to relieve her and discectomy was not
      required. The vault remained well supported despite removal of mesh.

PMID- 21887546
TI  - The clinical characteristics of uterine tumor-related bladder outlet obstruction.
AB  - INTRODUCTION AND HYPOTHESIS: The aim of this study was to assess the clinical
      characteristics of bladder outlet obstruction caused by uterine tumors. METHODS:
      We collected and analyzed data for eight patients who visited our urologic clinic
      due to voiding difficulty or acute urinary retention in the early morning and
      whose final, corroborated diagnoses were uterine tumors. Another eight patients
      with uterine tumor but without voiding symptoms were included as the controls.
      RESULTS: In group 1, six patients experienced acute early-morning urinary
      retention and two patients experienced severe early-morning voiding difficulty.
      This voiding difficulty lessened significantly during the day. All patients in
      group 1 received urodynamic studies which indicated a high detrusor voiding
      pressure (median, 28.5 cmH(2)O). The uroflowmetry test performed during the day
      showed a good maximal flow rate (median, 27 ml/s). Seven patients in group 1 who
      underwent surgery no longer had early-morning emptying symptoms. All tumors were
      located in the posterior uterine wall, in contrast to the control group whose
      tumors were located in fundus or anterior wall. CONCLUSIONS: Early-morning
      urinary retention or voiding difficulty can be considered as an important symptom
      of a uterine tumor obstructing the bladder outlet.

PMID- 21887547
TI  - Repair of vesicovaginal fistula by the transabdominal route: outcome at a north
      Indian tertiary hospital.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of this study is to present the outcome
      of management of vesicovaginal fistula (VVF) by the transabdominal route.
      METHODS: Between January 2001 and December 2010, 48 patients suffering from VVF
      were managed through the transabdominal route. RESULTS: The success rate
      following first repair was 87.5%. Patients who failed the first repair (n = 6)
      were managed again by the transabdominal route (second attempt). Two of these
      patients were cured, while another patient was cured after prolonged catheter
      drainage. One patient was managed by ureterosigmoidostomy (Mainz II) pouch but
      died after 6 months. The remaining two patients refused further treatment and
      were lost to follow-up. CONCLUSIONS: Transabdominal repair of VVF in properly
      selected patients results in satisfactory treatment outcome.

PMID- 21887548
TI  - Twelve months effect on voiding function of retropubic compared with outside-in
      and inside-out transobturator midurethral slings.
AB  - INTRODUCTION AND HYPOTHESIS: The purpose of this study is to compare retropubic
      tension-free vaginal tape (TVT) with transobturator out-in TOT and in-out TVT-O
      for female stress urinary incontinence. Uroflow rate was primary; continence
      rates, quality of life (QoL) and complication pattern were secondary endpoints.
      METHODS: A prospective randomised trial with 2:1:1 randomisation at two Swiss
      teaching hospitals. Patients were followed up at 12 months. RESULTS: Eighty TVT,
      40 transobturator tape (TOT) and 40 TVT-O were randomised. At 12 months, there
      was no difference in Qmax among the groups. Continence was comparable (>= 89%).
      QoL was improved significantly in all groups (P < 0.05). Five vaginal tape
      exposures occurred (one TVT, four TOT, zero TVT-O; P = 0.028). Two percent (1/52)
      of sexually active patients after TVT, 17% (5/29) after TOT, but 0% (0/25) after
      TVT-O reported de novo female sexual dysfunction (P = 0.011). We considered this
      clinically important enough to stop enrolment. CONCLUSIONS: There was no
      difference for Qmax at 12 months between TVT, TOT and TVT-O. Female sexual
      dysfunction and tape exposure may be higher with a transobturator tape.

PMID- 21887549
TI  - The impact of dispositional optimism on symptoms and treatment choices in
      patients with pelvic floor disorders.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study is to evaluate
      dispositional optimism, pelvic floor disorder symptoms, and treatment decisions.
      METHODS: Scores of the Life Orientation Test-Revised were used to categorize
      women seeking clinical treatment for pelvic floor disorders as pessimists (scores
      in lowest third) or optimists (scores in highest third). Participants also listed
      their treatment goals and quantified pelvic floor symptom severity by completing
      the Pelvic Floor Distress Inventory (PFDI-20). We compared symptoms, goals, and
      treatment choices between optimists and pessimists. RESULTS: Three hundred
      sixteen patients were included, 31% pessimists and 38% optimists. Pessimists
      reported more goals and different types of treatment goals. Pessimists were also
      more likely to elect surgical treatment over more conservative treatment methods,
      although this trend did not reach statistical significance. Among patients with
      prolapse (>=stage 2), PFDI-20 prolapse subscale scores were inversely correlated
      with level of optimism, with pessimists reporting a higher level of bother than
      optimists. CONCLUSIONS: In our study, pessimists reported more treatment goals,
      were more bothered by prolapse symptoms, and tended to be more likely to choose
      surgical treatments for their pelvic floor disorders than optimistic women.

PMID- 21887550
TI  - The time factor in the assessment of prolapse and levator ballooning.
AB  - INTRODUCTION AND HYPOTHESIS: The goal of the study was to define the time needed
      to obtain maximal organ descent and hiatal distension during Valsalva measured by
      transperineal ultrasound. Secondarily, we aimed to describe the timing of these
      events in relationship to each other. METHODS: We undertook a retrospective
      review of the stored ultrasound volume datasets of 50 patients with pelvic organ
      prolapse. Data on organ descent and hiatal distension were obtained in 10 volumes
      from rest to maximal Valsalva. RESULTS: On average, a Valsalva maneuver lasted
      9.4 s (range 5 to 18). It took patients on average about six volumes
      (approximately 5-6 s) to reach 80% of maximum organ descent. The time to maximum
      organ descent was 8.9 s and the time to maximum distension of the levator hiatus
      was 8.2 s, p = 0.031. CONCLUSIONS: In order to obtain adequate assessment of
      pelvic organ prolapse, a Valsalva maneuver should last at least 6 s. Hiatal
      distension seems to precede pelvic organ descent.

PMID- 21887551
TI  - TVT SECUR System: Final results of a prospective, observational, multicentric
      study.
AB  - INTRODUCTION AND HYPOTHESIS: This is an observational multicentre prospective
      study into the complications and effectiveness of TVT SECURTM. METHODS: One
      hundred forty-seven patients with urodynamic or occult Stress Urinary
      Incontinence (SUI) were enrolled. Outcome measures at 6, 12 and 24 months were:
      objective cough test; subjective responses to PGI-S questionnaire and Visual
      Analogue Score. STATISTICAL ANALYSIS: Wilcoxon Test; Monte Carlo Exact Test.
      RESULTS: Ninety-five urodynamic SUI and 41 occult SUI patients were treated using
      transobturator (H-position) or retropubic (U-position) approach (110 vs. 26
      patients). Cure rates at 6, 12, and 24 months were 87.5%, 88.6% and 89.5%.
      Failure rates at all follow-ups were similar for urodynamic and occult SUI. The U
      position failure rate was comparable to H-position at short-term but
      significantly higher at mid-term. Familiarity with the technique brought
      significantly higher success rates. CONCLUSIONS: TVT SECUR is safe, effective and
      versatile, but has an appreciable learning curve.

PMID- 21887552
TI  - The expression of PEBP4 protein in lung squamous cell carcinoma.
AB  - The phosphatidylethanolamine-binding protein 4 (PEBP4) is a member of the PEBP
      family. It not only plays a role in the inhibition of the MAPK signaling pathway
      but also is involved in the inhibition of the JNK pathway that promotes the
      activation of AKT. Recent research has also shown that overexpression of PEBP4
      was related to the development, invasion, and metastasis of a variety of tumors.
      This study aimed to investigate the correlation between PEBP4 protein expression
      in lung squamous cell carcinoma tissue and the clinical pathology of lung
      squamous cell carcinoma. Immunohistochemistry was used to detect PEBP4 expression
      in lung squamous cell carcinoma tissue and adjacent normal tissue from 61
      patients. Western blotting was used to detect changes in the expression of PEBP4
      protein between lung squamous cell carcinoma tissue and adjacent normal tissues.
      The correlation of PEBP4 expression and the occurrence, development, and clinical
      pathology of lung squamous cell carcinoma was analyzed. Of 61 patients, four
      patients were PEBP4 negative (-; 6.6%) and 57 patients were positive (+ to +++;
      93.4%). Of those positive for PEBP4 expression, 7 patients were weakly positive
      (+; 11.5%), 21 patients were positive (++; 34.4%), and 29 patients were strongly
      positive (+++; 47.5%). PEBP4 protein was more highly expressed in lung squamous
      cell carcinoma tissue than in the adjacent normal lung tissue (p < 0.05). In
      PEBP4-positive patients, PEBP4 protein expression was significantly greater in
      those with lymph node metastases than in those without (p < 0.05). PEBP4
      expression was significantly lower in patients at early (I and II) stages than in
      patients at advanced (III and IV) stages (p < 0.05). In less differentiated lung
      squamous cell carcinomas, PEBP4 protein expression was greater (p < 0.05);
      however, this was unrelated to the gender, age, or tumor size of the patient (p >
      0.05). PEBP4 protein overexpression was associated with the occurrence, invasion,
      and metastasis of lung squamous cell carcinoma.

PMID- 21887553
TI  - Polymorphisms in three obesity-related genes (LEP, LEPR, and PON1) and breast
      cancer risk: a meta-analysis.
AB  - Common genetic variations in the leptin (LEP), leptin receptor (LEPR), and
      paraoxonase 1 (PON1) genes have been considered to be implicated in the
      development of breast cancer. However, the results were inconsistent. In this
      study, a meta-analysis was performed to assess the associations of five
      polymorphisms, including LEP G2548A, LEPR Q223R, LEPR Lys109Arg, PON1 L55M, and
      PON1 Q192R polymorphisms, with breast cancer risk. Published literature from
      PubMed, ISI Web of Science, Embase databases, CNKI, and Wanfang Data were
      retrieved. All studies evaluating the association between LEP G2548A, LEPR Q223R,
      LEPR Lys109Arg, PON1 L55M, or PON1 Q192R polymorphism and breast cancer risk were
      included. Pooled odds ratio (OR) with 95% confidence interval (CI) was calculated
      using fixed- or random-effects model. Three studies (2,003 cases and 1,967
      controls) for LEP G2548A polymorphism, nine studies (4,627 cases and 5,476
      controls) for LEPR Q223R polymorphism, five studies (2,759 cases and 2,573
      controls) for LEPR Lys109Arg polymorphism, four studies (1,517 cases and 1,379
      controls) for PON1 L55M polymorphism, and five studies (1,575 cases and 2,283
      controls) for PON1 Q192R polymorphism were included in the meta-analysis.
      Overall, the results showed null significant association between LEP G2548A, LEPR
      Q223R, LEPR Lys109Arg, or PON1 Q192R polymorphism and breast cancer risk;
      however, PON1 L55M was significantly associated with breast cancer risk overall
      (MM vs. LL: OR = 2.16; 95% CI, 1.76-2.66). For LEPR Q223R polymorphism, further
      subgroup analysis suggested that the association was only statistically
      significant in East Asians (OR = 0.50; 95% CI, 0.36-0.70) but not in Caucasians
      (OR = 1.06; 95% CI, 0.77-1.45) or Africans (OR = 1.30; 95% CI, 0.83-2.03). The
      present meta-analysis suggested that LEPR Q223R polymorphism might be implicated
      in the development of breast cancer in East Asians; PON1 L55M might increase
      breast cancer risk. However, given the limited sample size, the findings warrant
      further investigation.

PMID- 21887554
TI  - SPARCL1: a potential molecule associated with tumor diagnosis, progression and
      prognosis of colorectal cancer.
AB  - We investigated whether SPARCL1 played an essential role in tumor initiation,
      formation and progression of colorectal carcinomas. In this study, we examined
      expression of SPARCL1 protein in the normal colorectal mucosa, adjacent normal
      mucosa and primary and lymph node metastases from colorectal cancer patients. In
      matched patients, we found that SPARCL1 was negative in the distant normal
      colorectal mucosa, weakly expressed in the adjacent normal mucosa, strongly
      expressed in primary colorectal adenocarcinomas and slightly expressed in their
      lymph node metastases. A similar pattern was observed in the SPARCL1 expression
      from our series of non-matched colorectal cancer patients. The strongest
      expression and highest frequency of the SPARCL1 protein were found in the primary
      cancers. Interestingly, in the primary tumors, the frequency of SPARCL1
      expression was significantly increased from the Dukes' A to Dukes' B tumors and
      then decreased gradually from the Dukes' B to C and D tumors. There was no
      difference in the intensity of SPARCL1 expression between the central areas and
      invasion margins of the primary tumors. Moreover, the SPARCL1 protein was more
      strongly expressed in the highly differentiated tumors than the lower
      differentiated ones. The patients with positive expression of SPARCL1 in their
      tumors had worse prognosis than the patients with SPARCL1-negative ones, even
      after the analyses by Multivariate and Interaction method. Expression of SPARCL1
      protein might be a valuable biomarker for early diagnosis in colorectal cancers
      and further predicting patients' prognosis.

PMID- 21887555
TI  - Single incision laparoscopic colorectal surgery: a single surgeon experience of
      102 consecutive cases.
AB  - BACKGROUND: Due to the recent heightened interest in even less invasive surgery,
      single port laparoscopic colorectal surgery is quickly gaining acceptance. While
      this access technique was first described in 2007 for colorectal resective
      procedures, large series are lacking. METHODS: Between January 2009 and October
      2010, all patients undergoing single port colorectal surgery performed by a
      single surgeon were prospectively entered into an IRB-approved database and
      studied with regard to perioperative events, morbidity, and mortality. RESULTS:
      One hundred and two consecutive patients underwent a single port colorectal
      procedure. Mean age was 47 years (9-93 years), and average body mass index was 26
      kg/m(2) (15-39 kg/m(2)). Primary diagnoses included ulcerative colitis (51),
      neoplasia (23), Crohn's disease (14), diverticulitis (11), familial adenomatous
      polyposis (1), and other (2). Procedures included 23 total colectomies, 40
      segmental colectomies, and 19 other procedures. There was 1 conversion to an open
      operation, and 18 (18%) patients required placement of additional ports (1 port:
      N = 13; 2 ports: N = 2; 3 ports: N = 3). Average operating room time was 99 min
      (13-245), mean length of incision was 3.7 cm (1.2-7.8 cm), and average estimated
      blood loss was 140 ml (0-750 ml). There was one postoperative death, and 39 (38%)
      patients experienced minor postoperative complications. Mean lymph node harvest
      for oncologic resections was 44 (14-142). The average length of hospital stay was
      5.9 days (2-24 days). CONCLUSIONS: With proper patient selection and laparoscopic
      experience, single port colorectal surgery can be performed for even the most
      complex colorectal procedures. Further studies are needed to assess the benefits
      that single port colorectal surgery has over a conventional laparoscopic
      approach.

PMID- 21887557
TI  - Malignancies of the anal canal.
AB  - BACKGROUND: The carcinomas of the anal canal consist of truly rare clinical
      entities compared to the most common colorectal malignancies. Consequently,
      little have been reported on their natural history and course. PURPOSE: The
      present study is aiming to describe the experience of our clinic with anal cancer
      and to clarify the incidence of the disease in the Hellenic population. MATERIAL
      AND METHODS: A 5-year retrospective study was conducted. We searched all cases of
      patients, diagnosed with anal carcinoma in our medical center. Medical records
      and histological examination results were all thoroughly registered and
      evaluated. RESULTS: On the whole, 60 patients were diagnosed with a malignant
      tumor of anal canal. Among them, 25 cases involved anal adenocarcinoma, 26 cases
      referred to a squamous cell carcinoma and in 5 cases, Bowen disease was
      identified. Two melanomas, one GIST stromal tumor and one case of Paget disease,
      were recognized as well. CONCLUSIONS: It seems that in our center the frequency
      and prevalence of anal adenocarcinoma is increased compared to the results from
      international data. More studies involving larger series of patients are required
      in order to shed further light in the true incidence of anal cancer and it
      subtypes in Hellenic population.

PMID- 21887556
TI  - Intraperitoneally administered irinotecan with 5-fluorouracil impair wound
      healing of colonic anastomoses in a rat model: an experimental study.
AB  - AIM: The aim of this experimental study is the assessment of the effects of the
      immediate post-operative intraperitoneal administration of 5-fluorouracil and
      irinotecan on the healing process of large bowel anastomoses in rats. MATERIALS
      AND METHODS: Sixty male Wistar rats were divided into 4 groups of 15 rats each.
      The rats underwent large bowel resection and anastomosis, followed by the
      intraperitoneal administration of normal saline (group 1), 5-fluorouracil (group
      2), irinotecan (group 3) or the combination of 5-fluorouracil and irinotecan
      (group 4). All animals were killed on the eighth post-operative day. During post
      mortem examination, the anastomoses were assessed macroscopically for a possible
      anastomotic leak and the extent of adhesion formation. Subsequently, the
      anastomotic bursting pressure was measured, and the anastomoses were assessed
      histologically. RESULTS: No anastomotic dehiscence was observed in the rats of
      group 1. In groups 2 and 3, we observed 3 anastomotic leaks in each group, and in
      group 4, we observed 5 leaks (P = 0.111). The mean bursting pressure of the
      anastomoses in group 1 was significantly higher compared to groups 2, 3 and 4 (P
      < 0.001). The least inflammatory cell infiltration score was observed in group 1
      (P < 0.001). The lowest neoangiogenesis score was observed in group 2 and the
      highest in group 4. The collagen formation in group 1 was significantly higher
      compared to the other 3 groups (P < 0.001). Similar results were observed for the
      fibroblast activity, where group 1 revealed significantly higher fibroblast
      scores compared to groups 2, 3 and 4 (P < 0.001). Finally, groups 2, 3 and 4
      showed significantly lower hydroxyproline levels compared to the control group (P
      < 0.001). CONCLUSION: The immediate, post-operative intraperitoneal
      administration of 5-fluorouracil or irinotecan had a negative effect on the
      healing process of the large bowel anastomoses in rats. The negative effects of
      the combination of 5-fluorouracil and irinotecan were statistically more
      significant compared to the single use of 5-fluorouracil or irinotecan.

PMID- 21887558
TI  - Acute appendicitis and carcinoid tumor in Meckel's diverticulum. Three
      pathologies in one: a case report.
AB  - Incidental carcinoid tumor of the Meckel's diverticulum is an uncommon event.
      Herein, a case of a carcinoid tumor in Meckel's diverticulum that was
      incidentally found in a patient with acute appendicitis is presented. A 42-year
      old Caucasian man presented with acute abdomen and clinical signs of acute
      appendicitis. A typical appendectomy was performed during which further abdominal
      exploration revealed a Meckel's diverticulum 60 cm proximal to the ileocecal
      valve, with an irregular and somewhat indurated serosal region on one side. A
      stapled diverticulectomy was performed. Pathology revealed an incidental
      carcinoid tumor measuring 1 cm within the Meckel's diverticulum. CT scan of the
      abdomen and 24-h urine 5-hydroxyindoleacetic acid results were normal. The
      patient had an uneventful recovery and was discharged at the 5th postoperative
      day. He is alive and without evidence of disease 23 months after the operation.
      Coexistence of acute appendicitis along with an incidental Meckel's diverticulum
      raises controversies in their surgical management. We discuss the issues in
      managing patients with two or more of these coexistent pathologies.

PMID- 21887559
TI  - Colorectal cancer surgery in the elderly: limitations and drawbacks.
AB  - PURPOSE: The purpose of this study was to evaluate the outcomes of colorectal
      cancer surgery among the elderly. METHODS: From March 2002 until February 2010,
      434 patients who presented to our institution with the initial diagnosis of
      colorectal cancer and were submitted to open curative colorectal cancer
      resections or some kind of palliative procedure either elective or emergencies
      were retrospectively reviewed. A total of 286 of these patients (65.8%) were
      below 75 years (group A) and 148 (34.2%) above 75 years (group B). RESULTS: A
      procedure with curative intent was undertaken in 386 patients (88.9%), while
      forty-eight patients (11.1%) were submitted to a palliative procedure. Regarding
      the incidence of emergency operations, forty-five patients (15.7%) from group A
      and forty-four patients (29.7%) from group B were operated due to an emergency
      (obstructing, perforating or bleeding tumors; P < 0.001). Mean ASA score was 1.74
      +/- 0.84 and 2.32 +/- 0.94 for groups A and B, respectively (P < 0.001). Mean TNM
      stage was 2.28 +/- 1.00 and 2.74 +/- 0.98 for groups A and B, respectively (P =
      0.0001). Elderly patients exhibited increased incidence of post-operative
      complications and increased post-operative mortality compared with their younger
      counterparts (P = 0.002 and 0.001, respectively). CONCLUSION: Colorectal cancer
      surgery in the elderly is a challenging clinical scenario. Treatment decision
      adjusted to each individual case is the ideal practice in order to maintain an
      acceptable balance between curative cancer resections and palliative procedures.

PMID- 21887560
TI  - General principles of hepatectomy in colorectal liver metastases.
AB  - Hepatic resection for colorectal liver metastases remains the only therapeutic
      option that improves long-term survival and offers potential cure. By
      conventional resectability criteria, only a limited number of patients with
      metastatic disease can be subjected to surgical intervention. In the past decade,
      better understanding of the natural history of the disease, the introduction of
      new chemotherapy agents and the advances in surgical techniques have led to more
      patients being eligible for surgery. Neoadjuvant chemotherapy can reduce the size
      of the metastases, allowing operation on patients who were previously considered
      inoperable. Major resections can nowadays be safely performed with the
      development of new less-invasive techniques and with the use of supplementary
      tools like ablation techniques. Using portal vein embolization to induce
      hypertrophy of future liver remnant and combining it with two-staged hepatectomy
      allow more patients with advanced disease to undergo potentially curative
      surgery. Careful selection of patients and aggressive surgery in experienced
      centers improve survival rates.

PMID- 21887561
TI  - Side-to-side anastomosis fashioned as stoma after sigmoid resection for sigmoid
      volvulus: a case report.
AB  - PURPOSE: Colonic volvulus is one of the causes of large bowel obstruction with
      sigmoid colon being the most usually affected part. Surgery is the gold standard
      when signs of peritonitis are present or endoscopic decompression fails.
      MATERIALS AND METHODS: We report the case of 65-year-old man with acute large
      bowel obstruction due to sigmoid volvulus who underwent a laparoscopic-assisted
      sigmoid resection on an emergency basis. The condition of the bowel wall
      precluded a primary anastomosis. But instead, a side-to-side anastomosis that its
      common blind stump was brought out as an end stoma was performed. RESULTS: The
      postoperative period was eventless. The patient was discharged on the 6th
      postoperative day. Eight weeks after the initial operation, the patient was
      readmitted for the secondary closure of the anastomotic stoma. Local anesthesia
      and minor sedation were enough in order to perform the stoma take down.
      CONCLUSION: Laparoscopic-assisted sigmoid resection is a useful adjunct to the
      surgical armamentarium when facing the problem of sigmoid volvulus. When a safe
      restoration of the alimentary tract continuity cannot be achieved safely with a
      primary anastomosis, the proposed anastomotic stoma technique is a useful and
      practical alternative.

PMID- 21887563
TI  - Surgical management of rectal prolapse.
AB  - PURPOSE: Rectal prolapse is uncommon; however, the true incidence is unknown
      because of underreporting, especially in the elderly population. Full-thickness
      rectal prolapse, mucosal prolapse and internal prolapse are three different
      clinical entities, which are often combined and constitute rectal prolapse. The
      aim of the study is to present our experience in the surgical management of
      rectal prolapse. METHODS: In a 6-year period (2004-2010), 27 patients were
      surgically treated for rectal prolapse. The majority of patients were women (25
      women, two men) and their mean age was 72.36 years. The operations performed were
      two Delorme's procedures, five STARR (Stapled TransAnal Rectal Resection), 14
      Wells procedures, two Wells combined with Thiersch, one Altemeier, one sigmoid
      resection combined with Wells and two Thiersch. RESULTS: An emergency
      sigmoidostomy was performed on a patient after Wells operation due to obstructive
      ileus. One death occurred on the 5th postoperative day due to pulmonary embolism.
      Two recurrences observed 8 months postoperatively, one in a patient after STARR
      operation and one in a patient after Thiersch technique. The great majority of
      patients are completely relieved of symptoms. CONCLUSIONS: The application of
      different modalities in the treatment of rectal prolapse is attributed to the
      fact that cause, degree of prolapse and symptoms, vary from one patient to
      another. Successful approach depends on many factors, including the status of a
      patient's anal sphincter muscle before surgery, whether the prolapse is internal
      or external and the overall condition of the patient.

PMID- 21887562
TI  - Laparoscopic colectomy for colonic carcinoma.
AB  - AIM: The aim of this study is to present our experience with the laparoscopic
      treatment approach for colonic carcinoma. PATIENTS AND METHODS: Between 2005 and
      2010, laparoscopic colectomy was performed in 13 patients; 9 patients underwent
      laparoscopic right hemicolectomy, 3 sigmoidectomy and 1 patient underwent
      laparoscopic caecectomy. RESULTS: With regards to the right hemicolectomies, the
      average operative time was 168 min and the average hospital stay 5.3 days. In
      patients who underwent laparoscopic sigmoidectomy, the average operative time was
      176 min, while the average hospital stay was 10.2 days. Finally, the laparoscopic
      caecectomy was performed in 85 min. There was one conversion (7.7%) to an open
      procedure, as well as one case (7.7%) of anastomotic leakage, which was treated
      with re-laparotomy and a Hartmann's procedure. Up to today, all patients remain
      healthy with no signs of tumor recurrence. CONCLUSION: Laparoscopic colectomy for
      cancer, in the hands of an experienced laparoscopic surgeon, is a safe and
      efficient procedure.

PMID- 21887564
TI  - Quality training in laparoscopic colorectal surgery: does it improve clinical
      outcome?
AB  - Laparoscopic colorectal surgery (LCRS) is a safe, effective and cost-efficient
      option for the treatment of various benign and malignant conditions. However, its
      implementation to surgical practice is still limited. That is mainly due to its
      association with a steep learning curve. We performed a review of the literature
      to determine whether quality training in LCRS can reduce that learning curve and
      lead to better clinical outcomes. We concluded that a structured training program
      with pre-clinical phase focused on basic skill acquisition and a clinical phase
      focused on mentoring from experts can shorten the learning curve and improve
      clinical outcomes.

PMID- 21887565
TI  - Current management of diverticular disease complications.
AB  - Diverticular disease is a common problem in the western population and sometimes
      leads to serious complications such as hemorrhage, bowel stenosis, obstruction,
      abscesses, fistulae, bowel perforation, and peritonitis. The severity of these
      complications can differ, and it is not always clear which procedure is indicated
      in each case and what measures should be followed before bringing the patient
      into the operating room. Certain operations have high rates of morbidity and
      mortality, especially in compromised patients. Along with advancements in imaging
      and minimally invasive techniques, the indications for surgery have currently
      being adapted to "damage limitation" or "down-staging" protocols, which seem to
      offer improved results. There are still some questions to be solved in the
      following years by prospective studies, such as the usefulness of laparoscopic
      lavage in purulent peritonitis or of Hartmann's procedure in fecal peritonitis.
      These indications, based on current literature, are systematically discussed in
      the present review.

PMID- 21887566
TI  - A retrospective analysis of 2000 cases with colorectal carcinoma.
AB  - PURPOSE: Colorectal cancer (CRC) is a major cause of death in the western world
      and a leading cause of cancer-related death. It is one of the most common human
      malignancies with >300,000 cases both in the United States and in the European
      Union each year. The present study was conducted to assess differences in various
      variables of CRC, such as location of the tumor, differentiation, Dukes
      classification, 5-year survival and possible changes in these patterns during the
      examined period. METHODS: We collected data on 2000 patients with colorectal
      cancer, diagnosed and treated from 1960 to 2008 in 1st Propedeutic Surgical
      Clinic of Aristotle's University, Thessaloniki. RESULTS: Of 2000 cases reviewed,
      cancer was almost equal presented to both sexes, for all groups. Rectum was the
      most common tumor location in all analyzed groups (40.1%). The most common tumor
      differentiation was the moderate one (68.5%). Concerning tumor staging, Dukes' B
      tumors were most common (42.5%), and the cancer-related 5-year survival was
      increased by the time from 42 to 71%. CONCLUSION: In the past 20 years,
      considerable improvements have been made in colorectal cancer therapy, and
      patients had received more sophisticated and multidisciplinary treatments,
      resulting in a better 5-year survival rate.

PMID- 21887567
TI  - Rectal endometriosis: a case report.
AB  - We present the case of a 45-year-old female patient who was admitted with a
      history of pelvic pain, constipation, and dysmenorrhea. CT scan and u/s images
      revealed cholelithiasis, benign nodular hyperplasia of segment IV of the liver
      and uterine fibromyoma. During laparotomy, firm adhesions between the posterior
      wall of the uterus and the rectum were found and the incisional biopsy reveals an
      undifferentiated adenocarcinoma. Then, total resection of the uterus was
      performed with en block resection of the adherent part of the rectum and part of
      the posterior wall of the vagina. The final histopathological report showed the
      presence of uterine fibromyoma, nodular hyperplasia of the liver and rectal
      endometriosis without any sign of malignancy. The patient after 5 years of follow
      up remains healthy. Rectal endometriosis represents an uncommon localization of
      pelvic endometriosis where the symptoms and clinical findings are non-specific
      making the definitive preoperative diagnosis difficult. Endometriosis should be
      included in the differential diagnosis of chronic pelvic pain in combination with
      defecation disorders in female patients of reproductive age.

PMID- 21887568
TI  - Cecal volvulus after twin gestation: laparoscopic approach.
AB  - INTRODUCTION: Intestinal obstruction in pregnancy is not common. Colonic volvulus
      occurs in 24% of such cases. Due to the rare incidence and lack of imaging during
      pregnancy, correct diagnosis is often delayed. CASE PRESENTATION: We present a
      case of a 33-year-old female with a twin pregnancy gestation, who presented with
      acute abdominal pain. Physical examination revealed a gravid uterus and
      tenderness in the lower abdominal quadrants. Due to intense uterine contractions,
      the patient was urgently submitted to cesarean delivery, giving birth to two
      healthy infants. Twelve hours after the cesarean section, right lower quadrant
      abdominal pain was persistently severe. Nausea, vomiting, diarrhea, and abdominal
      dilatation were also present. Abdominal X-ray and CT scan showed bowel
      obstruction, possibly secondary to cecal volvulus. The patient was subjected to
      explorative laparoscopy, cecal volvulus detorsion, and laparoscopic appendectomy.
      RESULTS: The postoperative course was uneventful, and the patient was discharged
      on the fourth postoperative day. CONCLUSIONS: Cecal volvulus in pregnancy is a
      rare, difficult to diagnose, clinical entity. It is associated with high
      morbidity and mortality, both of mother and fetus, because of delayed diagnosis.
      A high index of clinical suspicion is required in pregnant or puerperant women
      with signs and symptoms of bowel obstruction and persistent pain at the right low
      abdominal quadrant. As long as diagnosis is timely set, laparoscopy is a safe and
      successful means of surgical treatment.

PMID- 21887569
TI  - The stapled hemorrhoidopexy syndrome: a new clinical entity?
AB  - PURPOSE: Haemorrhoidal disease is a rather common disease of unknown cause. A new
      technique for treating prolapsing haemorrhoids known as the stapled
      hemorrhoidopexy (SH) or the "Longo procedure" is widely used. Serious adverse
      events were reported in 2000 and some discussion over the syndrome but nothing
      since. METHODS: Two hundred and five patients underwent SH by our surgical team
      at the Interbalkan European Medical Center. Modified SH was performed. RESULTS:
      Despite the low incidence of postoperative complications (11/205), 36.58% of
      patients developed syndrome comprised of urgency to defecate, sensation of anal
      foreign body and incomplete defecation and mild cramp like anal discomfort,
      immediately after surgery or in the following 48 h. There is not statistically
      significant relationship between the presence of the syndrome and the gender, the
      presence of muscle fibres in the resected "ring" the degree of haemorrhoidal
      disease, age and ring length. CONCLUSION: Observations led us to conclude that
      the stapled hemorrhoidopexy syndrome (SHS) is probably caused by the irritating
      presence of the titanium staples in the rectal mucosa and by the resection
      itself.

PMID- 21887571
TI  - Colonic lipomas: our experience in diagnosis and treatment.
AB  - AIM: The aim of this study is to present our experience in colonic lipomas.
      PATIENTS AND METHODS: We present 4 patients (1 male, 3 females) of mean age 65.5
      years (range, 61-72 years) treated for single colonic lipomas. The diameters of
      the lesions were 4.5, 4, 3.5 and 2.5 cm, respectively. In 3 cases, colonic
      lipomas were located within the cecum, while in one patient within the descending
      colon, proximally to the splenic flexure. RESULTS: Lipomas of diameter greater
      than 3 cm caused nonspecific symptoms. Lipomas of higher diameter were removed
      laparoscopically with colotomy; in two cases, the patients underwent open
      hemicolectomy, because of the suspicion of malignancy, while the smallest lesion
      was resected endoscopically, using a bipolar snare. All patients recovered
      without complications and remain healthy with no signs of recurrence. CONCLUSION:
      In cases of ulcerated lipomas, greater than 3 cm of diameter, surgical resection
      is recommended.

PMID- 21887570
TI  - Clinical features of colonic diverticular disease.
AB  - Colonic diverticular disease is extremely common in developed countries. Although
      the majority of patients with diverticulosis remain asymptomatic, about one-third
      of the patients manifest the disease with either hemorrhage or inflammation.
      Diverticulitis may be uncomplicated or complicated by abscess formation,
      perforation with peritonitis, fistula, intestinal obstruction, or stricture.
      Controversy exists regarding the aggressiveness of diverticulitis during
      recurrent attacks of the disease as well as in special groups of patients
      including immunocompromised patients, young patients, and patients with right
      sided disease. Clinical characteristics of symptomatic uncomplicated disease can
      be similar to irritable bowel syndrome, while acute diverticulitis is sometimes
      difficult to distinguish from segmental colitis associated with diverticulosis.
      The considerable clinical overlap between those entities with diverticular
      disease demonstrates that there are still areas of uncertainty in their
      physiopathology.

PMID- 21887572
TI  - Gossypiboma presenting as mesosigmoid abscess [corrected].
AB  - INTRODUCTION: The term "gossypiboma" is used to describe any mass of non
      absorbable surgical material. It is estimated that this complication appears
      every 1.000-10.000 procedures. It may lead to peritonitis, acute abdominal pain,
      intraperitoneal abscess, bowel obstruction, or perforation. REPORT OF A CASE: We
      present the case of an 80-year-old female patient admitted for chronic abdominal
      pain and fever. A CT scan and MRI were performed with a probable diagnosis of
      carcinoma or pelvic abscess. A surgical history of hysterectomy and repair of
      abdominal wall hernia with a mesh were mentioned. RESULTS: Exploratory laparotomy
      revealed the presence of an irregular, soft mass with characteristics of an
      abscess located into the mesosigmoid. Hartman's sigmoidectomy was performed, and
      the patient's postoperative course was uneventful. The histopathological
      examination confirmed the diagnosis of gossypiboma. CONCLUSIONS: Retained foreign
      intraperitoneal materials often represent diagnostic dilemmas, since
      symptomatology is no specific and the time elapsed from surgery is long. The
      policy of prevention's importance is highly appreciated.

PMID- 21887573
TI  - Surgical management of colorectal injuries: colostomy or primary repair?
AB  - PURPOSE: Several factors have been considered important for the decision between
      diversion and primary repair in the surgical management of colorectal injuries.
      The aim of this study is to clarify whether patients with colorectal injuries
      need diversion or not. METHODS: From 2008 to 2010, ten patients with colorectal
      injuries were surgically treated by primary repair or by a staged repair.
      RESULTS: The patients were five men and five women, with median age 40 years (20
      55). Two men and two women had rectal injuries, while 6 patients had colon
      injuries. The mechanism of trauma in two patients was firearm injuries, in two
      patients was a stab injury, in four patients was a motor vehicle accident, in one
      woman was iatrogenic injury during vaginal delivery, and one case was the
      transanal foreign body insertion. Primary repair was possible in six patients,
      while diversion was necessary in four patients. CONCLUSIONS: Primary repair
      should be attempted in the initial surgical management of all penetrating colon
      and intraperitoneal rectal injuries. Diversion of colonic injuries should only be
      considered if the colon tissue itself is inappropriate for repair due to severe
      edema or ischemia. The role of diversion in the management of unrepaired
      extraperitoneal rectal injuries and in cases with anal sphincter injuries is
      mandatory.

PMID- 21887574
TI  - Management of concurrent colorectal cancer and vascular disease in the
      endovascular era.
AB  - Concurrent colorectal cancer (CRC) and vascular disease, such as abdominal aortic
      aneurysm, represents a challenging clinical situation. Both lesions may lead to
      the demise of the patient and therefore should be treated. Endovascular
      techniques may enhance decision-making and even permit single-stage treatment.
      PATIENTS AND METHODS: Retrospective review of patients in a university department
      with extensive endovascular experience. Between 2004 and 2010, seven patients
      with synchronous vascular disease and colorectal cancer were identified. RESULTS:
      The mean age was 73 years, and all patients were men. Five patients had
      concurrent CRC and aneurysmal disease. Two had synchronous critical carotid
      artery stenosis and CRC. All vascular lesions were treated with endovascular
      techniques. All CRC were resected with open techniques. In four patients,
      endovascular repair followed by staged CRC resection was performed. In three
      patients, single-stage procedures were performed. There was one perioperative
      death, for a mortality of 14.3% in our series. There were no graft infections.
      CONCLUSIONS: Priority of treating concurrent vascular disease and CRC remains a
      dilemma. Combined treatment with a single-stage procedure is feasible. Risk of
      graft infection may be lower than expected.

PMID- 21887575
TI  - Changes in treatment of rectal cancer: increased use of low anterior resection.
AB  - PURPOSE: The most common surgical procedures for patients with rectal cancer are
      low anterior resection (LAR) or abdominoperineal excision (APE). The aim of the
      present study is to evaluate and report the changes in the incidence of LAR and
      APE in the surgical treatment of rectal cancer over the last 15 years in a single
      surgical department. METHODS: The patient sample consisted of 251 consecutive
      patients (mean age 65.17; age range 22-87) that underwent surgical treatment for
      rectal cancer in a single center from 1996 to 2010. This time frame was divided
      into three 5-year periods (1996-2000, 2001-2005 and 2006-2010). Patients were
      classified into one of the aforementioned groups, depending on the date of their
      treatment. RESULTS: In the first period (1996-2000), 71 patients were treated for
      rectal cancer. Among them, 32.4% (n = 23) underwent an abdominoperineal excision
      (APE) while 56.3% (n = 40) were treated with LAR. In the second period (2001
      2005), included 102 patients, from which 29.4% (n = 30) received an APE and 60.8%
      (n = 62) underwent a LAR for their disease. In the final period (2006-2010), from
      the 78 patients, only 12.8% (n = 10) of them underwent APE, while 74.3% (n = 58)
      were treated with LAR. There was a statistically significant (chi-square test, P
      = 0.005) difference between the 3 periods of time concerning the performance of
      LAR and APE. CONCLUSIONS: According to the results of the present study, the
      rates of APE seem to decrease during the last 15 years, while LAR is more widely
      used in the surgical treatment of rectal cancer.

PMID- 21887576
TI  - Inflammation of solitary caecal diverticula:a rare aetiology of acute abdominal
      pain [corrected].
AB  - Caecal diverticula are rare, representing the 3.6% of colonic diverticula. They
      may have congenital origin and remain asymptomatic, presenting as an accidental
      finding. We present a case of a 42-year-old Caucasian woman, admitted with a 12-h
      history of sudden onset of sharp right iliac fossa pain, anorexia, and nausea.
      There was leukocytosis (23.49 * 10(3)/MUl) and increased C-reactive protein
      (11.76 mg/dl). CT scan showed an inflamed appendix. At laparotomy, a diffuse
      caecal phlegmon with an inflammatory solitary caecal diverticula was found. A
      limited right hemicolectomy was performed. Histological examination confirmed the
      caecal diverticulitis without malignancy. Post-operative period was uneventful.
      Three months later, endoscopy showed no diverticula or other pathologies.
      Solitary caecal diverticulum is very rare, but surgeons must bear this in mind in
      case of pain in right iliac fossa.

PMID- 21887577
TI  - Outcomes of Doppler-guided hemorrhoid artery ligation: analysis of 90 consecutive
      patients.
AB  - BACKGROUND: Doppler-guided hemorrhoid artery ligation is a minimal-invasive
      surgical treatment option for hemorrhoidal disease. The aim of our study was to
      evaluate the early and long-term results of the procedure 1 year after the
      operation. PATIENTS AND METHODS: In a period of 4 years, 90 patients were
      included in this study. The Doppler-guided hemorrhoid artery ligation was
      performed under either spinal anesthesia or local perianal block. We recorded the
      length of postoperative inpatient care, on-demand analgesics administered apart
      from the standard analgesic protocol, short- and long-term complications, and,
      finally, recurrences. RESULTS: The mean age of patients was 46 +/- 12.6 years.
      The operation was performed under spinal anesthesia in 82 patients and under
      local perianal block in 8 patients. The mean operative time was 26 +/- 4.1 min.
      On-demand analgesics administration was reported in sixteen patients (17.7%) the
      first postoperative day and in four patients (4.4%) the second postoperative day.
      A total of 58 patients (64.4%) were discharged from the hospital the day of the
      operation, 29 (32.2%) patients stayed overnight, and in three (3.3%) patients, a
      hospitalization period of 2 days was needed. Four patients (4.4%), two with grade
      III and two with grade IV hemorrhoids, developed early postoperative
      complications. Late complications were observed in three patients (3.3%).
      Recurrences, manifested either as bleeding or as prolapsing piles, were observed
      in six patients (6.6%), two patients with initial grade III and four with grade
      IV hemorrhoids. CONCLUSION: Doppler-guided hemorrhoid artery ligation seems to be
      a safe and effective treatment option for all grades of hemorrhoidal disease.
      Further prospective randomized comparative studies are needed in order to fully
      evaluate the true role of DG-HAL in the surgical armamentarium.

PMID- 21887578
TI  - Modern pathophysiology and treatment of esophageal diverticula.
AB  - INTRODUCTION: Esophageal diverticula are rare. They may occur in the
      pharyngoesophageal area (Zenker's), midesophagus, or distally (epiphrenic). A
      motility disorder (either at the level of the esophageal sphincters or body) is
      frequently associated with esophageal diverticula. The risk of malignant
      transformation is low. METHODS: A literature search was performed using
      Medline/PubMed database. RESULTS: The treatment of esophageal diverticula must be
      based on the pathophysiology and natural history of the disease: (a) asymptomatic
      diverticula do not need a specific treatment, (b) small diverticula may be left
      in place and not resected, (c) medium-size diverticula may be either treated by
      diverticulectomy, diverticulopexy, or esophagodiverticulostomy in case of
      pharyngoesophageal diverticula, (d) resection is probably the ideal therapy for
      larger diverticula, and (e) a myotomy should always be included to the procedure.
      CONCLUSIONS: Due to its rarity, esophageal diverticula must be treated by
      esophageal surgeons since even in experienced hands the complication rate can be
      significant.

PMID- 21887579
TI  - Cytochrome P450-derived epoxyeicosatrienoic acids accelerate wound
      epithelialization and neovascularization in the hairless mouse ear wound model.
AB  - PURPOSE: Epoxyeicosatrienoic acids (EETs) are known to modulate proliferation and
      angiogenesis in vitro. Tissue levels of EETs are regulated by the cytochrome P450
      (CYP) epoxygenases that generate them as well as by the soluble epoxide hydrolase
      metabolizes them to their less active diols. The aim of this study was to
      determine the effect of locally administered EETs (11,12- and 14,15-EETs) and the
      selective sEH inhibitor (sEHI) trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]
      benzoic acid (t-AUCB) on wound healing in vivo. METHODS: Standardized full
      thickness dermal wounds were created on the dorsum of hairless mouse ears. Wound
      epithelialization was directly viewed and measured using intravitalmicroscopy and
      computerized planimetry every second day until healing was complete. Wound
      sections were analyzed by immunostaining for endothelial lineage marker CD31,
      vascular endothelial growth factor (VEGF), and angiogenic cytokine stromal cell
      derived factor (SDF) 1alpha on days 2, 4, and 13. RESULTS: Treatment with EETs
      and t-AUCB, respectively, significantly accelerated wound epithelialization and
      neovascularization by synergistic upregulation of SDF1alpha and VEGF in vivo.
      CONCLUSIONS: These findings demonstrated that exogenous CYP-derived EETs and
      globally decreased EET hydrolysis by sEH inhibition significantly accelerated
      wound epithelialization and neovascularization in unimpaired healing wounds.
      Given that hypoxia induces CYP expression and subsequently EET-dependent
      angiogenesis, EETs and sEHIs provide a promising new class of therapeutics for
      ischemic non-healing wounds.

PMID- 21887580
TI  - Transcriptional dynamics during cell wall removal and regeneration reveals key
      genes involved in cell wall development in rice.
AB  - Efficient and cost-effective conversion of plant biomass to usable forms of
      energy requires a thorough understanding of cell wall biosynthesis, modification
      and degradation. To elucidate these processes, we assessed the expression
      dynamics during enzymatic removal and regeneration of rice cell walls in
      suspension cells over time. In total, 928 genes exhibited significant up
      regulation during cell wall removal, whereas, 79 genes were up-regulated during
      cell wall regeneration. Both gene sets are enriched for kinases, transcription
      factors and genes predicted to be involved in cell wall-related functions.
      Integration of the gene expression datasets with a catalog of known and/or
      predicted biochemical pathways from rice, revealed metabolic and hormonal
      pathways involved in cell wall degradation and regeneration. Rice lines carrying
      Tos17 mutations in genes up-regulated during cell wall removal exhibit dwarf
      phenotypes. Many of the genes up-regulated during cell wall development are also
      up-regulated in response to infection and environmental perturbations indicating
      a coordinated response to diverse types of stress.

PMID- 21887581
TI  - Prevalence of specific learning disabilities among primary school children in a
      South Indian city.
AB  - OBJECTIVE: To measure the prevalence of specific learning disabilities (SpLDs)
      such as dyslexia, dysgraphia and dyscalculia among primary school children in a
      South Indian city. METHODS: A cross-sectional multi-staged stratified randomized
      cluster sampling study was conducted among children aged 8-11 years from third
      and fourth standard. A six level screening approach that commenced with
      identification of scholastic backwardness followed by stepwise exclusion of
      impaired vision and hearing, chronic medical conditions and subnormal
      intelligence was carried out among these children. In the final step, the
      remaining children were subjected to specific tests for reading, comprehension,
      writing and mathematical calculation. RESULTS: The prevalence of specific
      learning disabilities was 15.17% in sampled children, whereas 12.5%, 11.2% and
      10.5% had dysgraphia, dyslexia and dyscalculia respectively. CONCLUSIONS: This
      study suggests that the prevalence of SpLDs is at the higher side of previous
      estimations in India. The study is unique due to its large geographically
      representative design and identification of the problem using simplified
      screening approach and tools, which minimizes the number and time of specialist
      requirement and spares the expensive investigation. This approach and tools are
      suitable for field situations and resource scarce settings. Based on the authors'
      experience, they express the need for more prevalence studies, remedial education
      and policy interventions to manage SpLDs at main stream educational system to
      improve the school performance in Indian children.

PMID- 21887582
TI  - Contraceptive method choice among youth in the United States: the importance of
      relationship context.
AB  - We examine the relationship characteristics associated with contraceptive method
      choice within young people's nonmarital sexual relationships, using data from
      retrospective relationship histories available in the third wave (2001-2002) of
      the National Longitudinal Study of Adolescent Health. Data-reduction techniques
      produce a detailed multidimensional characterization of relationship commitment
      for nonmarital sexual relationships. We then use multilevel analysis to estimate
      associations between two key relationship characteristics-relationship commitment
      and couple heterogamy-and the type of contraceptive method used at last sexual
      intercourse within each relationship. Results indicate that for a given
      individual, contraceptive method choice varies across relationships as a function
      of these characteristics, even after we account for important individual and
      family characteristics and prior relationship experiences.

PMID- 21887583
TI  - Marital shopping and epidemic AIDS.
AB  - HIV risks decline sharply at age 30 for women in South Africa, long before coital
      frequencies or pregnancies decrease. I evaluate several prominent behavioral
      models of HIV, and find that these do not suggest sharply decreasing risks with
      age. I formulate a model of spousal search and find that "marital shopping" can
      generate epidemic HIV prevalence despite low transmission rates because search
      behavior interacts with dynamics of HIV infectiousness. The implied age-infection
      profile closely mimics that in South Africa, and the suggested behavior matches
      that reported by South Africans. Condom use in new relationships and transmission
      rate reductions are both found to be effective policies and, when used together,
      eliminate the potential of spousal search to spread HIV. In contrast,
      antiretroviral treatment is found to have only a minimal effect on the epidemic.

PMID- 21887584
TI  - The habitual use of the Self-report Habit Index.

PMID- 21887586
TI  - Sexual stereotypes and practices of university students in Turkey.
AB  - This article is based on a study of young people and sexuality in Turkey. The
      focus of this study included messages about sexuality, sexual beliefs, sexual
      experiences with a view to consent and resistance, religiosity, and certain
      interrelations therein. A total of 471 students (273 women, M age=20.5 years, and
      198 men, M age=21 years) from four different universities in Turkey participated
      in a survey with measures of restrictive and permissive messages about sexuality
      received from various sources, beliefs about sexual roles of men and women in
      relationships, and questions about a range of sexual experiences, including
      coital and non-coital. The incidence and characteristics of ideal sexual
      partnership and incidence and dynamics of experiences involving "token
      resistance" and "consent to unwanted sex" were specifically investigated. The
      results provided a snapshot of the sexual lives of students in this country at
      the crossroads of secularism and traditional Muslim mores. Both commonalities and
      differences were found across gender. Both men and women received more
      restrictive than permissive messages. The most important message source was same
      sex friends for men and parents for women. Men had more dating and sexual
      partners than women. The correlations of religiosity and messages with sexual
      experiences and attitudes were mostly in the expected direction. Women were more
      likely to have a token resistance incidence and both genders were equally
      unlikely to consent to unwanted sex. The results were discussed in relation to
      the cultural context and the relevant literature, and recommendations are offered
      for future research.

PMID- 21887585
TI  - 'I've had unsafe sex so many times why bother being safe now?': the role of
      cognitions in sexual risk among American Indian/Alaska Native men who have sex
      with men.
AB  - BACKGROUND: American Indian/Alaska Native (AI/AN) men who have sex with men (MSM)
      are at high risk of human immunodeficiency virus (HIV) acquisition and
      transmission. PURPOSE: This study aimed to investigate a potential area of focus
      for HIV prevention interventions by assessing the impact of sexual risk
      cognitions on sexual risk-taking among AI/AN MSM. METHODS: AI/AN MSM (N = 173)
      from a national cross-sectional survey were analyzed. RESULTS: Reporting more
      frequent sexual risk cognitions overall (high sexual risk cognitions) was
      associated with multiple HIV risk factors including unprotected anal intercourse
      and serodiscordant unprotected anal intercourse. Participants with high sexual
      risk cognitions had a 2.3 (95% Confidence Interval: 1.1, 4.7) times greater odds
      of engaging in unprotected anal intercourse regardless of childhood sexual abuse,
      depression, and alcohol dependence. Most individual sexual risk cognitions were
      associated with unprotected anal intercourse, serodiscordant unprotected anal
      intercourse, or both. CONCLUSIONS: Results suggest that sexual risk cognitions
      may be a productive area for further work on HIV prevention among AI/AN MSM.

PMID- 21887587
TI  - Sex differences and similarities in married couples: patterns across and within
      cultures.
AB  - In this study, we examined the patterns of sex differences in men and women
      married to each other in five cultures (China, Russia, Turkey, UK, and the U.S.)
      to look for universal patterns in behavioral dimorphisms and for cultural
      variability in those patterns. Over 400 couples in each cultural group completed
      the 235-item Marriage and Relationship Questionnaire on various aspects of
      marriage, appropriately translated for each culture. Sex differences were
      anticipated in responses related to female choosiness, labor performed, emotional
      expressiveness, interest in sex, physical attractiveness, and jealousy. To
      measure male-female differences in each culture, t-tests were utilized, and
      effect sizes were calculated. Significant sex differences (p < .05, two-tailed)
      emerged in all six areas examined, although cultural differences were also seen
      in the patterns. For example, on items relevant to female choosiness, women in
      most, but not all, cultures were more likely than their husbands to endorse these
      statements: "I have thought of divorcing my spouse" and "My parents played a role
      in choosing my spouse." In China, where scores on emotional expressiveness were
      low, sex differences disappeared in the category related to emotions. Results
      suggest that long-term marriage exhibits a balance between homogamy and
      dimorphism serving reproductive interests. Moreover, culture may moderate this
      balance for particular sex differences.

PMID- 21887588
TI  - Finite element analysis of donning procedure of a prosthetic transfemoral socket.
AB  - Lower limb amputation is a severe psychological and physical event in a patient.
      A prosthetic solution can be provided but should respond to a patient-specific
      need to accommodate for the geometrical and biomechanical specificities. A new
      approach to calculate the stress-strain state at the interaction between the
      socket and the stump of five transfemoral amputees is presented. In this study
      the socket donning procedure is modeled using an explicit finite element method
      based on the patient-specific geometry obtained from CT and laser scan data. Over
      stumps the mean maximum pressure is 4 kPa (SD 1.7) and the mean maximum shear
      stresses are 1.4 kPa (SD 0.6) and 0.6 kPa (SD 0.3) in longitudinal and
      circumferential directions, respectively. Locations of the maximum values are
      according to pressure zones at the sockets. The stress-strain states obtained in
      this study can be considered more reliable than others, since there are normal
      and tangential stresses associated to the socket donning procedure.

PMID- 21887589
TI  - Photothermal cancer therapy and imaging based on gold nanorods.
AB  - Gold nanorods (GNRs), which strongly absorb near-infrared (NIR) light, have shown
      great potential in fields of biomedical application. These include photothermal
      therapy, molecular imaging, biosensing, and gene delivery, especially for the
      treatment of diseased tissues such as cancer. These biomedical applications of
      GNRs arise from their various useful properties; photothermal (nanoheater)
      properties, efficient large scale synthesis, easy functionalization, and
      colloidal stability. In addition, GNRs do not decompose and have an enhanced
      scattering signal and tunable longitudinal plasmon absorption which allow them to
      be used as a stable contrast agent. Therefore, GNRs are also promising
      theranostic agents, combining both tumor diagnosis and treatment. In this review,
      we discuss the recent progress of in vitro and in vivo explorations of the
      diagnostic and therapeutic applications of GNRs as a component of cancer therapy.

PMID- 21887590
TI  - Lensfree optofluidic microscopy and tomography.
AB  - Microfluidic devices aim at miniaturizing, automating, and lowering the cost of
      chemical and biological sample manipulation and detection, hence creating new
      opportunities for lab-on-a-chip platforms. Recently, optofluidic devices have
      also emerged where optics is used to enhance the functionality and the
      performance of microfluidic components in general. Lensfree imaging within
      microfluidic channels is one such optofluidic platform, and in this article, we
      focus on the holographic implementation of lensfree optofluidic microscopy and
      tomography, which might provide a simpler and more powerful solution for three
      dimensional (3D) on-chip imaging. This lensfree optofluidic imaging platform
      utilizes partially coherent digital in-line holography to allow phase and
      amplitude imaging of specimens flowing through micro-channels, and takes
      advantage of the fluidic flow to achieve higher spatial resolution imaging
      compared to a stationary specimen on the same chip. In addition to this, 3D
      tomographic images of the same samples can also be reconstructed by capturing
      lensfree projection images of the samples at various illumination angles as a
      function of the fluidic flow. Based on lensfree digital holographic imaging, this
      optofluidic microscopy and tomography concept could be valuable especially for
      providing a compact, yet powerful toolset for lab-on-a-chip devices.

PMID- 21887592
TI  - Are we exacerbating students' learning disabilities? an investigation of
      preservice teachers' attributions of the educational outcomes of students with
      learning disabilities.
AB  - While claims of the importance of attribution theory and teachers' expectations
      of students for student performance are repeatedly made, there is little
      comprehensive research identifying the perceptions preservice teachers have of
      students with learning disabilities (LD). Accordingly, 444 Australian preservice
      primary school teachers were surveyed using vignettes and Likert-scale questions,
      to ascertain their responses to students with and without LD. It was found that
      preservice primary school general education teachers held a negative attribution
      style towards students with LD. Preservice primary teachers perceived students
      with LD as a lacking ability in comparison to others in the class.
      Recommendations for research and training programmes conclude the paper.

PMID- 21887591
TI  - A switch between cytoprotective and cytotoxic autophagy in the radiosensitization
      of breast tumor cells by chloroquine and vitamin D.
AB  - Calcitriol or 1,25-dihydroxyvitamin D3, the hormonally active form of vitamin D,
      as well as vitamin D analogs, has been shown to increase sensitivity to ionizing
      radiation in breast tumor cells. The current studies indicate that the
      combination of 1,25-dihydroxyvitamin D3 with radiation appears to kill p53 wild
      type, estrogen receptor-positive ZR-75-1 breast tumor cells through autophagy.
      Minimal apoptosis was observed based on cell morphology by DAPI and TUNEL
      staining, annexin/PI analysis, caspase-3, and PARP cleavage as well as cell cycle
      analysis. Induction of autophagy was indicated by increased acridine orange
      staining, RFP-LC3 redistribution, and detection of autophagic vesicles by
      electron microscopy, while autophagic flux was monitored based on p62
      degradation. The autophagy inhibitors, chloroquine and bafilomycin A1, as well as
      genetic suppression of the autophagic signaling proteins Atg5 or Atg 7 attenuated
      the impact of the combination treatment of 1,25 D3 with radiation. In contrast to
      autophagy mediating the effects of the combination treatment, the autophagy
      induced by radiation alone was apparently cytoprotective in that either
      pharmacological or genetic inhibition increased sensitivity to radiation. These
      studies support the potential utility of vitamin D for improving the impact of
      radiation for breast cancer therapy, support the feasibility of combining
      chloroquine with radiation for the treatment of breast cancer, and demonstrate
      the existence of an "autophagic switch" from cytoprotective autophagy with
      radiation alone to cytotoxic autophagy with the 1,25 D3-radiation combination.

PMID- 21887593
TI  - The elevated serum S100A8/A9 during acute myocardial infarction is not of cardiac
      myocyte origin.
AB  - Overproduction of circulating S100A8/A9 occurs in patients following acute
      myocardial infarction (AMI). It remains unclear whether ischemia insult per se
      induces S100A8 and S100A9 expression in cardiac myocytes or even whether the
      cardiac myocytes participate as a source of these proteins. In this study,
      western blot analysis and quantitative real-time reverse transcription polymerase
      chain reaction were used to test samples obtained from isolated spontaneously
      hypertensive rat hearts and Wistar-Kyoto rat hearts subjected to global
      normothermic ischemia and from neonatal Wistar rat cardiac myocytes undergoing
      hypoxia. Ischemia did not increase the expression of S100A8 and S100A9 proteins
      and mRNA in the myocardium either from the spontaneously hypertensive rat hearts
      or the Wistar-Kyoto rat hearts. In addition, the levels of S100A8 and S100A9
      proteins were unchanged in the neonatal rat cardiac myocytes undergoing hypoxia.
      However, both ischemia and hypoxia activated NF-kappaB in ischemic myocardium and
      in hypoxic cardiac cells in a time-dependent manner. The results suggest that the
      increased serum S100A8/A9 concentrations following AMI were not of cardiac
      myocyte origin.

PMID- 21887594
TI  - Performance and carcass measurements of ewe lambs reared in a feedlot and fed
      wheat (Triticum durum Desf.) middlings total mixed rations in the summer season.
AB  - The effect of total mixed ratios containing wheat middlings (WM) as a corn grain
      substitute on the growth performance and carcass traits of Comisana ewe lambs was
      evaluated. Forty ewe lambs, with average live body weight of 13 +/- 0.3 kg (mean
      +/- SEM), were allocated randomly to two isocaloric and isonitrogenous diets for
      50 days. Control diet contained 400 g/kg of dry matter (DM) of corn as the main
      starchy source, whereas experimental diet contained 600 g/kg DM of WM. In vivo
      nutrient apparent digestibility of the two diets was determined using Comisana
      rams (mean body weight, 65 +/- 2.3 kg) and indicated significant (P < 0.05)
      differences for neutral detergent fibre, acid detergent fibre, cellulose and
      hemicellulose fractions. Results from the trial using Comisana ewe lambs showed
      that growth traits were unaffected by dietary treatments as well as none of the
      carcass measurements examined (P > 0.05). These findings indicate that WM results
      as a suitable feed ingredient for growing ewe lambs that can be a satisfactory
      substitute to conventional grain source.

PMID- 21887595
TI  - Seroprevalence of Toxoplasma gondii antibodies from slaughter pigs in Chongqing,
      China.
AB  - Toxoplasmosis is a disease caused by the protozoan Toxoplasma gondii which
      infects most genera of warm-blooded animals, including humans. The objective of
      this investigation is to evaluate the seroprevalence of toxoplasmosis in pigs in
      Chongqing Municipality, southwest China. Slaughterhouse pigs' serum samples
      collected from six different regions in Chongqing were assayed for T. gondii
      antibodies by an indirect hemagglutination test. The average seroprevalence of T.
      gondii were found in 30.6% (278/908) in slaughter pigs, ranging from 21.6% to
      40.9% among different sampling sites. The results indicated that toxoplasmosis in
      swine of Chongqing Municipality was relatively serious, and the pork may be an
      important source for human infection with T. gondii. Comprehensive measures are
      needed to strengthen further prevention and control of the disease in Chongqing.

PMID- 21887596
TI  - Obesity increases the prevalence and severity of focal knee abnormalities
      diagnosed using 3T MRI in middle-aged subjects--data from the Osteoarthritis
      Initiative.
AB  - OBJECTIVE: To study the effect of BMI on the prevalence, severity, and 36-month
      progression of early degenerative changes in the knee by using 3T MRI in middle
      aged subjects without radiographic osteoarthritis (OA). MATERIALS AND METHODS: We
      examined baseline and 36-month follow-up MR studies from 137 middle-aged
      individuals (45-55 years old) with risk factors for knee OA but no radiographic
      OA from the Osteoarthritis Initiative. Subjects were grouped into three
      categories: normal BMI (BMI < 25 kg/m(2), n = 38), overweight (BMI 25-29.9
      kg/m(2), n = 37), and obese (BMI >= 30 kg/m(2), n = 62). Using 3T MRI, cartilage,
      meniscus, and bone marrow abnormalities were graded using the OA Whole-organ MR
      Imaging Score (WORMS). The statistical analysis was corrected as necessary for
      differences in age, sex, and OA risk factors other than BMI. RESULTS: The overall
      prevalence of lesions was 64% for meniscus and 79% for cartilage (including low
      grade lesions). At baseline, the prevalence and severity of knee lesions was
      positively associated with BMI, with a nearly fourfold increase in meniscal tears
      and more than twofold increase in high-grade cartilage defects in obese
      individuals relative to normal-weight subjects. Over the 36-month follow-up
      period, the number of new or worsening cartilage lesions of any grade was
      significantly higher in obese subjects (p = 0.039), while there was no
      significant difference in meniscal lesion progression. CONCLUSION: Obesity was
      associated with both higher prevalence and severity of early degenerative changes
      in the knee in middle-aged individuals without radiographic OA and with
      significantly increased cartilage lesion progression (of any grade) over 36
      months.

PMID- 21887597
TI  - Subcutaneous absorption of monoclonal antibodies: role of dose, site of
      injection, and injection volume on rituximab pharmacokinetics in rats.
AB  - PURPOSE: To determine the effect of dose, the anatomical site of injection, and
      the injection volume on subcutaneous absorption of rituximab in rats and to
      explore absorption mechanisms using pharmacokinetic modeling. METHODS: Rituximab
      serum concentrations were measured following intravenous and subcutaneous
      administration at the back, abdomen, and foot of rats. Several pharmacokinetic
      models were developed that included linear and saturable absorption, and
      degradation and/or protective binding at the injection site. RESULTS: Rituximab
      exhibited linear kinetics following intravenous administration; however,
      bioavailability following subcutaneous injection was inversely related to the
      dose level. For the 1 mg/kg dose, bioavailability was approximately 70% at all
      tested injection sites, with faster absorption from the foot (T(max) = 12 h for
      foot vs. 4.6 days for back). Bioavailability for the 10 mg/kg dose was 44 and 31%
      for the abdomen and back sites and 18% for 40 mg/kg injected at the back. A
      pharmacokinetic model that included binding as part of the absorption mechanism
      successfully captured the nonlinearities in rituximab absorption. CONCLUSION: The
      anatomical site of subcutaneous injection influences the rate of absorption and
      bioavailability of rituximab in rats. Saturable binding may be a major
      determinant of the nonlinear absorptive transport of monoclonal antibodies.

PMID- 21887598
TI  - Development of effective cancer vaccine using targeting system of antigen protein
      to APCs.
AB  - PURPOSE: To develop a novel cancer vaccine using the targeting system of antigen
      protein to antigen-presenting cells (APCs) for efficient and safe cancer therapy.
      METHODS: The novel delivery system was constructed with antigen protein,
      benzalkonium chloride (BK), and gamma-polyglutamic acid (gamma-PGA), using
      ovalbumin (OVA) as a model antigen protein and evaluating its immune induction
      effects and utilities for cancer vaccine. RESULTS: BK and gamma-PGA enabled
      encapsulation of OVA and formed stable anionic particles at nanoscale,
      OVA/BK/gamma-PGA complex. Complex was taken up by dendritic cell line DC2.4 cells
      efficiently. We subcutaneously administered the complex to mice and examined
      induction of IgGs. The complex induced not only Th2-type immunoglobulins but also
      Th1-type immunoglobulins. OVA/BK/gamma-PGA complex inhibited tumor growth of E.G7
      cells expressing OVA regularly; administered OVA/BK/gamma-PGA complex completely
      rejected tumor cells. CONCLUSION: The novel vaccine could be platform technology
      for a cancer vaccine.

PMID- 21887599
TI  - Influence of bias on visuospatial and verbal compatibility effects in mixed
      mapping environments.
AB  - The advantage for the compatible mapping of physical locations or arrows to
      keypresses is reduced when trials with compatible and incompatible mappings are
      mixed, whereas the advantage is increased for location words. We evaluated
      explanations of these mixing effects by varying the proportions of compatible and
      incompatible trials for groups performing with each stimulus mode. The mappings
      were compatible on 75%, 50%, and 25% of the trials, respectively, for compatibly
      biased, unbiased, and incompatibly biased conditions. For locations and arrows,
      compatible bias increased the SRC effect, and incompatible bias reduced the
      effect; for location words, the incompatible bias was stronger than the
      compatible one. Reaction time distributions showed that, with locations and
      arrows, initial activation toward either the compatible (unbiased condition) or
      the predominant (biased conditions) response was transient. With words,
      activation of the corresponding response increased across the distribution,
      regardless of bias condition. The influence of bias on the SRC effects was
      relatively independent of the mixing and sequential effects, and was different
      for words than for nonwords. These results are consistent with the view that
      visuospatial stimuli produce transient activation of the corresponding or
      predominant response, whereas location words produce phonological activation,
      required for word identification, that persists.

PMID- 21887600
TI  - Forecasting the economic benefit of reducing non-operative time.

PMID- 21887601
TI  - [Validation of the French version of the non-communicating children's pain
      checklist - postoperative version].
AB  - PURPOSE: The aim of the study was to test the validity of a French language
      version of the Non-Communicating Children's Pain Checklist - Postoperative
      Version (NCCPC-PV): grille d'evaluation de la douleur-deficience intellectuelle
      (GED-DI). METHODS: We assessed the intensity of pain in 87 intellectually
      disabled surgical patients recruited in four Canadian and French hospitals in the
      pre- and post-operative settings using the GED-DI, a 100-mm visual analogue pain
      scale (VAS) and the Rosen sedation scale. The validity of the GED-DI was measured
      by the difference in scores between pre- and postoperative conditions. The
      checklist was made up of 30 items divided into seven subgroups. Items were rated
      from 0 to 3 for a total score ranging from 0 to 90 points. RESULTS: The mean
      (standard deviation) age of the patients was 17 (11) yr and the mean mental age
      24.5 (24) months. The total GED-DI score was 6.1 (4.9) pre- and 13.4 (11.2) post
      surgery (P < 0.001). All subgroups had a higher score after surgery (P < 0.001).
      The receiver operating characteristic (ROC) curves, comparing the absence of pain
      to mild pain scores and moderate to severe pain scores, showed a cutoff at 6
      (mild pain) and 11 (moderate to severe pain). CONCLUSION: The French version of
      the NCCPC-PV can be used to assess pain in non-communicating patients with
      intellectual disabilities in a postoperative setting. It has good content
      validity, as the total pre-surgery score for the GED-DI was significantly lower
      than the postoperative score, and showed a good concurrent validity when compared
      to the VAS.

PMID- 21887602
TI  - Sevoflurane and desflurane protect cholinergic-induced bronchoconstriction of
      hyperreactive airways in rabbits.
AB  - PURPOSE: The potential of desflurane to alter respiratory mechanics in the
      presence of bronchial hyperresponsiveness (BHR) is still a subject of debate.
      Accordingly, we evaluated the bronchoprotective potential of desflurane compared
      with sevoflurane following cholinergic lung constriction in rabbits with normal
      and hyperreactive airways. METHODS: The input impedance of the respiratory system
      (Zrs) was measured during midazolam-based anesthesia before and during
      intravenous infusions of increasing doses of methacholine (MCh). The rabbits in
      the control group (Group C) were then randomized to receive either sevoflurane 1
      MAC followed by desflurane 1 MAC or vice versa, whereas ovalbumin-sensitized
      rabbits received sevoflurane followed by desflurane (Group S-SD) or vice versa
      (Group S-DS). Baseline Zrs measurements and the MCh provocations were repeated
      under the maintenance of each volatile agent. Airway resistance (Raw), tissue
      damping (G), and elastance data were obtained from Zrs by model fitting. RESULTS:
      Similar bronchoprotective effects of sevoflurane and desflurane against MCh
      induced bronchoconstriction were observed independently of the severity of the
      bronchospasm and the presence of BHR. With sevoflurane, the decreases in Raw
      ranged from 22 (8.8)% to 44 (12)%, and with desflurane, they ranged from 22
      (8.7)% to 50 (12)%. The increases in G reflecting the enhanced ventilation
      heterogeneities in the lung periphery were not affected by the volatile agents.
      CONCLUSIONS: If the contractile stimulus is cholinergic in origin, sevoflurane
      and desflurane exert similar bronchoprotective potentials to act against lung
      constriction independent of the presence of BHR. These volatile anesthetics
      otherwise lack a potential to improve the enhanced ventilation heterogeneities
      that develop particularly in the presence of BHR.

PMID- 21887604
TI  - Radiation and ethylene oxide terminal sterilization experiences with drug eluting
      stent products.
AB  - Radiation and ethylene oxide terminal sterilization are the two most frequently
      used processes in the medical device industry to render product within the final
      sterile barrier package free from viable microorganisms. They are efficacious,
      safe, and efficient approaches to the manufacture of sterile product. Terminal
      sterilization is routinely applied to a wide variety of commodity healthcare
      products (drapes, gowns, etc.) and implantable medical devices (bare metal
      stents, heart valves, vessel closure devices, etc.) along with products used
      during implantation procedures (catheters, guidewires, etc.). Terminal
      sterilization is also routinely used for processing combination products where
      devices, drugs, and/or biologics are combined on a single product. High patient
      safety, robust standards, routine process controls, and low-cost manufacturing
      are appealing aspects of terminal sterilization. As the field of combination
      products continues to expand and evolve, opportunity exists to expand the
      application of terminal sterilization to new combination products. Material
      compatibility challenges must be overcome to realize these opportunities. This
      article introduces the reader to terminal sterilization concepts, technologies,
      and the related standards that span different industries (pharmaceutical, medical
      device, biopharmaceuticals, etc.) and provides guidance on the application of
      these technologies. Guidance and examples of the application of terminal
      sterilization are discussed using experiences with drug eluting stents and
      bioresorbable vascular restoration devices. The examples provide insight into
      selecting the sterilization method, developing the process around it, and finally
      qualifying/validating the product in preparation for regulatory approval and
      commercialization. Future activities, including new sterilization technologies,
      are briefly discussed.

PMID- 21887603
TI  - Ethylcellulose-based matrix-type microspheres: influence of plasticizer RATIO as
      pore-forming agent.
AB  - In this study, ethylcellulose (EC)-based microsphere formulations were prepared
      without and with triethyl citrate (TEC) content of 10% and 30% by water-in-oil
      emulsion-solvent evaporation technique. Diltiazem hydrochloride (DH) was chosen
      as a hydrophilic model drug and used at different drug/polymer ratios in the
      microspheres. The aim of the work was to evaluate the influence of plasticizer
      ratio on the drug release rate and physicochemical characteristics of EC-based
      matrix-type microspheres. The resulting microspheres were evaluated for
      encapsulation efficiency, particle size and size distribution, surface
      morphology, total pore volume, thermal characteristics, drug release rates, and
      release mechanism. Results indicated that the physicochemical properties of
      microspheres were strongly affected by the drug/polymer ratio investigated and
      the concentration of TEC used in the production technique. The surface morphology
      and pore volume of microspheres significantly varied based on the plasticizer
      content in the formulation. DH release rate from EC-based matrix-type
      microspheres can be controlled by varying the DH to polymer and plasticizer
      ratios. Glass transition temperature values tended to decrease in conjunction
      with increasing amounts of TEC. Consequently, the various characteristics of the
      EC microspheres could be modified based on the plasticized ratio of TEC.

PMID- 21887605
TI  - Use of the Gerchberg-Saxton algorithm in optimal coherent anti-Stokes Raman
      spectroscopy.
AB  - We are utilizing recent advances in ultrafast laser technology and recent
      discoveries in optimal shaping of laser pulses to significantly enhance the stand
      off detection of explosives via control of molecular processes at the quantum
      level. Optimal dynamic detection of explosives is a method whereby the
      selectivity and sensitivity of any of a number of nonlinear spectroscopic methods
      are enhanced using optimal shaping of ultrafast laser pulses. We have recently
      investigated the Gerchberg-Saxton algorithm as a method to very quickly estimate
      the optimal spectral phase for a given analyte from its spontaneous Raman
      spectrum and the ultrafast laser pulse spectrum. Results for obtaining selective
      coherent anti-Stokes Raman spectra (CARS) for an analyte in a mixture, while
      suppressing the CARS signals from the other mixture components, are compared for
      the Gerchberg-Saxton method versus previously obtained results from closed-loop
      machine-learning optimization using evolutionary strategies.

PMID- 21887606
TI  - Cation exchange HPLC analysis of desmosines in elastin hydrolysates.
AB  - Desmosine crosslinks are responsible for the elastic properties of connective
      tissues in lungs and cardiovascular system and are often compromised in disease
      states. We developed a new, fast, and simple cation exchange HPLC assay for the
      analysis of desmosine and isodesmosine in animal elastin. The method was
      validated by determining linearity, accuracy, precision, and desmosines stability
      and was applied to measure levels of desmosines in porcine and murine organs. The
      detection and quantification limits were 2 and 4 pmol, respectively. The run-time
      was 8 min. Our cation exchange column does not separate desmosine and
      isodesmosine, but their level can be quantified from absorbance at different
      wavelengths. Using this assay, we found that desmosines levels were significantly
      lower in elastin isolated from various organs of immunodeficient severe combined
      immunodeficiency mice compared with wild-type animals. We also found that
      desmosines levels were lower in lung elastin isolated from hyperhomocysteinemic
      Pcft(-/-) mice deficient in intestinal folate transport compared with wild-type
      Pcft(+/+) animals.

PMID- 21887607
TI  - Button botany: plasmodesmata in vegetable ivory.
AB  - The hard endosperm of species of the palm genus Phytelephas (elephant plant),
      known as vegetable ivory, was used in the manufacture of buttons in the
      nineteenth century, the early twentieth century, and again in more recent times.
      Here, we show that the pathways for intercellular communication, including the
      cytoplasm in opposite pits and the plasmodesmata that traverse the cell wall, can
      be visualized in century-old inexpensive buttons that are readily available in
      antique shops.

PMID- 21887608
TI  - Detection of asymptomatic adenocarcinoma at endoscopy prior to gastric banding
      justifies routine endoscopy.
AB  - BACKGROUND: Pre-operative upper gastrointestinal (GI) endoscopy prior to gastric
      banding surgery remains controversial. We report the finding of asymptomatic
      oesophageal adenocarcinomas detected at pre-operative endoscopy in our unit.
      METHODS: Data from a prospectively maintained database concerning the period May
      2003 to October 2010 were reviewed. We identified 371 patients who had undergone
      upper GI endoscopy prior to gastric banding. Endoscopy reports were reviewed to
      identify any pathology detected. RESULTS: Endoscopy revealed abnormalities in 207
      (56%) patients. A range of abnormalities were detected, the most significant of
      which were two asymptomatic oesophageal adenocarcinomas. CONCLUSIONS: The
      detection of two early, asymptomatic oesophageal adenocarcinomas in a high risk
      patient group justifies our policy of routine upper GI endoscopy prior to gastric
      banding surgery.

PMID- 21887610
TI  - Comparing central retinal thickness in diabetic macular edema measured by two
      different spectral-domain optical coherence tomography devices.
AB  - PURPOSE: We evaluated central retinal thickness (CRT) in diabetic macular edema
      (DME) using two different spectral-domain (SD) optical coherence tomography (OCT)
      instruments: the Cirrus and Spectralis OCTs. METHODS: CRT was measured in 63 eyes
      of 32 patients with DME using both instruments on the same day. RESULTS: CRT
      measurements were significantly greater for the Spectralis than the Cirrus (p <
      0.0003, n = 63, paired t test); mean CRT values were 382 +/- 136 MUm with the
      Cirrus and 394 +/- 139 MUm with the Spectralis. In eyes with poor best-corrected
      visual acuity (BCVA) (<20/40), mean CRT was 378 +/- 130 MUm with the Cirrus and
      395 +/- 139 MUm with the Spectralis (p < 0.007, n = 29). In eyes with good acuity
      (equal to or better than 20/40), the mean CRT was 385 +/- 142 MUm with the Cirrus
      and 393 +/- 140 MUm with the Spectralis (p < 0.005, n = 34). CONCLUSIONS: Foveal
      retinal thickness measurements may vary among SD-OCT devices. The differences
      between instruments could affect the results of a multicenter study.

PMID- 21887609
TI  - Cutting-edge issues in organ-specific autoimmunity.
AB  - There have been numerous methods and ways to classify autoimmune diseases. By
      far, the most traditional has been to separate immune-mediated pathology into
      organ-specific and organ-non-specific diseases. The classic systemic autoimmune
      diseases are, of course, rheumatoid arthritis and systemic lupus. The classic
      organ-specific autoimmune diseases have been autoimmune thyroiditis and
      autoimmune gastritis. However, as our understanding of the loss of tolerance has
      expanded, so has the long list of autoimmune diseases. In many cases, the
      distinction between organ-specific and organ-non-specific or systemic
      autoimmunity becomes a blur. In this issue, we discuss recent concepts in
      autoimmune pancreatitis, primary sclerosing cholangitis, Goodpasture's syndrome,
      myofasciitis, type I diabetes, polymyositis, autoimmune thyroid disease, IgA
      nephropathy, autoimmune uveitis, and ANCA-associated vasculitis. Common themes on
      both etiology and effector mechanisms are described throughout these papers with
      an attempt to provide a cutting-edge overview.

PMID- 21887611
TI  - Peculiarities of clinical profile of snoring and mild to moderate obstructive
      sleep apnea-hypopnea syndrome patients.
AB  - PURPOSE: The purpose of this study is to perform comprehensive evaluation of the
      snoring and mild to moderate obstructive sleep apnea-hypopnea syndrome (OSAHS)
      patients for their anatomical, functional, and psychoemotional clinical
      properties. METHODS: Seventy-four snoring patients, aged 24 to 64 (mean 41.83 +/-
      11.01) years underwent full-night polysomnography, nasopharyngoscopy, and Mueller
      maneuver. Clinical tests battery consisting of visual analogue scales (VAS)
      scales, Lithuanian version of Sleep Apnea Quality of Life Index (SAQLI-LT),
      Spielberg's State-Trait Anxiety Inventory (STAI), Beck Depression Inventory
      Second Edition (BDI-II), and Epworth Sleepiness Scale (ESS) were applied to
      assess their distinctive clinical properties. RESULTS: The total group of snoring
      and mild to moderate OSAHS patients presented with considerably enlarged VAS
      snoring and daytime sleepiness scores (mean 66.32 +/- 19.07 and 35.03 +/- 27.83
      points), mild BDI-II scores (mean 10.96 +/- 9.42 points), and moderate trait
      anxiety scores (mean 41.51 +/- 8.62 points). All the scores of daytime complaints
      measured with the VAS correlated statistically significantly with the mean scores
      of the ESS, SAQLI-LT, trait anxiety, and BDI-II. Both groups, of snoring and mild
      to moderate OSAHS patients, indicated similar intensity of the major complaints
      according to the VAS, same as similar BDI-II, STAI, and SAQLI-LT scores. A higher
      Friedman's score of palatal tonsils was found in the group of snoring patients,
      comparing to that of the group of mild to moderate OSAHS patients (p < 0.05).
      CONCLUSIONS: Snoring and mild to moderate OSAHS patients have resemblances in
      their distinctive anatomical and clinical properties. This group of the patients
      revealed mild depression and moderate trait anxiety scores when measured with the
      BDI-II and STAI, which correlated significantly with the severity of the
      patients' daytime complaints measured with the VAS.

PMID- 21887612
TI  - Gene * environment interactions in type 2 diabetes.
AB  - People vary genetically in their susceptibility to the effects of environmental
      risk factors for many diseases. Genetic variation also underlies the extent to
      which people respond appropriately to clinical therapies. Defining the basis to
      the interactions between the genome and the environment may help elucidate the
      biologic basis to diseases such as type 2 diabetes, as well as help target
      preventive therapies and treatments. This review examines 1) some of the most
      current evidence on gene * environment interactions in relation to type 2
      diabetes; 2) outlines how the availability of information on gene * environment
      interactions might help improve the prevention and treatment of type 2 diabetes;
      and 3) discusses existing and emerging strategies that might enhance our ability
      to detect and exploit gene * environment interactions in complex disease traits.

PMID- 21887613
TI  - [Dental medicine in transition].

PMID- 21887614
TI  - [Guidelines and recommendations from scientific associations within a European
      context].
AB  - Guidelines and recommendations are increasingly impacting day-to-day clinical
      care in medicine and dentistry. Although guidelines are only meant to define a
      range of treatment measures that have been proven to be medically useful, they
      can have a significant impact on both health care politics and reimbursement
      strategies as well as be misused to direct particular treatment modalities into
      the hands of certain specialties. Because these effects tend to not only
      negatively influence the acceptance but also impair the implementation of
      guidelines, the process of guideline compilation has to be transparent and based
      on clearly defined methodology. The German Association of Dental and
      Craniomandibular Sciences ("Deutsche Gesellschaft fur Zahn-, Mund- und
      Kieferheilkunde", DGZMK) is the umbrella organization of all scientific dental
      associations in Germany, and initiating new guideline projects as well as
      continuously updating existing guidelines is one of one of its major tasks. These
      activities are pursued in cooperation with the "Zahnarztliche Zentralstelle
      Qualitatssicherung" (ZZQ) and the "Arbeitsgemeinschaft wissenschaftlich
      medizinischer Fachgesellschaften" (AWMF).

PMID- 21887615
TI  - [Oral health in Germany: an oral epidemiological outline].
AB  - The article describes the current situation with regard to oral health in Germany
      on the basis of selected surveys. The analysis is confined to the two main oral
      diseases, i.e., dental caries and periodontitis. At the same, data on the rates
      of restorative procedures are presented and trends in the development of
      prevalences are addressed. Whereas in Germany caries (crown caries) is clearly
      declining as a burden of disease, the situation with respect to the prevalence of
      periodontitis is unclear; however, the undertreatment of people having
      periodontitis in Germany must be assumed. Tooth loss among the adult population
      in Germany has decreased considerably.

PMID- 21887616
TI  - [Dental health in the United Kingdom and influencing variables].
AB  - OBJECTIVE: To review four key topics pertaining to the oral health of the United
      Kingdom (UK): (1) provision of state-funded dentistry, (2) trends in oral health,
      (3) dental caries prevention, and (4) determinants of dental health. METHODS:
      Data were abstracted, mainly from peer-reviewed publications in the literature.
      Information was updated where appropriate. RESULTS: Since the 1948 inception of
      the National Health Service (NHS) and its General Dental Service (GDS), the
      system of providing dentistry has evolved in response to changing fiscal and
      health circumstances. Since the 1970s, the oral health of the population, both
      children's dental decay experience and the decline adult tooth loss, has improved
      steadily and substantially. Approaches towards prevention are discussed and the
      dominant position of water fluoridation highlighted. The determinants of dental
      health are analysed. CONCLUSION: Dental caries experience of children in the UK
      and the rest of Europe is highly correlated with national wealth as are two other
      significant determinants: fluoride toothpaste and sugar consumption. The activity
      of dental professionals appears to have only a limited influence on levels of
      oral health. There is reason to believe that UK water fluoridation coverage may
      broaden.

PMID- 21887617
TI  - [The profile of the dentist in science and practice: based on the new dental
      licensure act].
AB  - The profession of dentistry developed essentially based on the rapid progress of
      research in general. With the law of dentistry in 1952, the dentist became an
      independent profession in Germany. The EU directive 2005/36 for recognition of
      professional qualifications now regulates the requirements for practicing as a
      dentist in the European Union. Today, dentistry is a scientifically based medical
      discipline which has increased its preventive, diagnostic, and therapeutic
      possibilities especially over the last 3 decades. The implementation is carried
      out in dental practice under the framework and basic conditions of present health
      care policy and conditions. A new order regulating licenses to practice dentistry
      is under development in which the first 2 years will be nearly identical with the
      studies of medicine and the medical licensure act. The closer orientation toward
      medicine is reasonable as more multimorbid patients will have a need for dental
      treatment in daily practice and co-operation with physicians will be more
      frequent in the future. New occupational profiles in dentistry are proposed above
      the level of a graduated dentist as well as below but also in completely new
      noncurative areas.

PMID- 21887618
TI  - [Dental education in Germany: new concepts for the dental curriculum].
AB  - In Germany, the dental curriculum is still based on dental licensing regulations
      ("Approbations-/Prufungsordnung fur Zahnarzte") from 1955. Essential changes of
      the dental licensing regulations have not been made for over 50 years-unlike the
      medical licensing regulations in Germany. Teaching and learning concepts have,
      nevertheless, changed considerably in medical and dental education over time. The
      present study delivers an analysis about reform initiatives in dental education
      in Germany and introduces examples of innovative projects. To be able to
      establish long-term and broad reforms in dental education, new licensing
      regulations for dentists are required. This should create a contemporary
      framework for education, which assigns resources and enables occupational profile
      development at specific locations. Thereby, compatibility with the medical
      curriculum has to be guaranteed just as required adaptations of admission and
      curricular capacity regulations for dentistry.

PMID- 21887619
TI  - [German dental and postgraduate education in the European context].
AB  - The dental curriculum in Germany is still based on a concept from 1955 with some
      revisions in certain aspects. All groups involved are interested in a new and
      more current version. In doing this, the compatibility with European concepts
      should be a main goal. The Association for Dental Education in Europe (ADEE), to
      which about 160 of the 200 European dental education associations are members, is
      in charge of coordinating projects to create a network of European universities,
      which intends to harmonize higher education in Europe and to create a core
      curriculum for the dentistry program. Based on a visitation and evaluation
      program at more than 50 oral and maxillofacial surgery centers, a paper for the
      profiles and competencies for future European dentists was formulated for the
      creation of a modular curriculum, for the integration of the ECT (European Credit
      Transfer) system, and for quality assurance of the dentistry curriculum.
      Especially for the situation in Germany, consequences must be drawn for further
      dentistry and postgraduate educational concepts, which are not completely
      identical with the ADEE concepts, but which can use elements of the basic Bologna
      concepts.

PMID- 21887620
TI  - [Oral medicine: a specialty placed between medicine and dentistry].
AB  - Oral medicine is a dental specialty that bridges the traditional areas of health
      between dentistry and medicine. International descriptions reflect this and oral
      medicine is defined as "the dental speciality placed at the interface between
      medicine and dentistry and is concerned with the diagnosis and management of (non
      dental) pathology affecting the oral and maxillofacial region." Oral medicine
      specialists provide clinical care to patients with a wide variety of orofacial
      conditions, including oral mucosal diseases, orofacial pain syndromes, salivary
      gland disorders, and oral manifestations of systemic diseases. There is a growing
      need to implement this specialty globally: due to the rapid progress in both
      medicine and dentistry, and to the growing percentage of senior citizens in many
      countries, the adequate diagnosis and treatment of oral diseases will become even
      more complex in the future. In this article, the authors' intention is to point
      out that oral medicine is neither a recognized specialty nor a distinct field of
      study in Germany, Austria, or Switzerland; thus, the need for postgraduate
      training in this field in countries where oral medicine is not a specialization
      is emphasized.

PMID- 21887621
TI  - [Medically compromised patients in the dental office: demographics and progress
      in health care].
AB  - Due to changing demographics in our society, there are an increasing number of
      patients with risk factors presenting for dental care. Unfortunately valid
      screening instruments to identify these patients are lacking. Especially in
      elderly patients, there is often an association between the high number of
      prescribed medications and oral symptoms. Using supportive therapy in oncology
      (e.g., radio(chemo)therapy) as an example, the role of modern dentistry and its
      interaction with general medicine is illustrated. Modern substances, e.g.,
      antiangiogenetics, with still unknown side effects represent challenging new
      developments in the field of oral medicine. Even with some examples of positive
      representation of patients with risk factors in the health systems, e.g., S 28
      SGB V, it is clear that the pressure on the costs in the health systems leads to
      an undertreatment of patients with risk factors. Only by adapting dental and
      postgraduate training with respect to these aspects, together with better
      financial reimbursement of the additional efforts, will this trend be overcome.

PMID- 21887622
TI  - [Special care dentistry for dependent elderly and people with disabilities].
AB  - In 2009, 7.1 million people (8% of the population) were officially recognized as
      having severe disabilities in the Federal Republic of Germany. At the same time,
      about 2.34 million Germans were in need of special care with some overlap between
      these groups. Although structured preventive programs in Germany helped to
      improve oral health generally (DMS IV 2006), care recipients and people with
      disabilities did not benefit to the same extent from this development. They often
      show a higher risk of caries and periodontal diseases due to both a lack of
      compliance and insufficient personal plaque control. It is desirable that care
      recipients and persons with disabilities attain the same level of oral health as
      persons without impairments. All care givers ought to be aware of the dental
      problems of these groups and should be sufficiently trained to deal with them.
      Dental care should compensate any deficits to ultimately attain the same standard
      of oral health. To achieve these goals, ease of access to dental care as well as
      dental services appropriate to the impairments have to be established.

PMID- 21887623
TI  - [Current concepts in diagnosis and treatment of oral malignant tumors].
AB  - This article offers a short review of risk factors, oral precancerous conditions,
      and oral precancerous lesions which may cause oral squamous carcinoma. Current
      diagnostic methods and multidisciplinary strategies for the early detection and
      appropriate therapy of oral squamous carcinomas are discussed. Close cooperation
      of oral and maxillofacial surgeons, head and neck surgeons, radiotherapists, and
      oncologists is essential for the effective therapy of oral squamous carcinomas.

PMID- 21887624
TI  - [Relationship between periodontitis and systemic diseases].
AB  - Periodontitis is a biofilm-induced inflammatory disease affecting the
      periodontium with a high and even increasing prevalence in the German population.
      During recent years, there is emerging evidence for systemic effects of a
      periodontal infection, in particular in relation to diabetes and atherosclerosis.
      There is a bi-directional relationship between periodontitis and diabetes.
      Diabetes promotes the occurrence, the progression, and the severity of
      periodontitis. The periodontal infection complicates the glycemic control in
      diabetes, increases the risk of diabetes-associated complications and possibly
      even of its onset. As a consequence, the treatment of periodontal infections
      should become an integral part of the management of diabetes, whereas glycemic
      control is a prerequisite for successful periodontal therapy. Periodontal
      infections are considered as independent risk factor for atherosclerosis and
      their clinical sequelae, e.g., cerebro- and cardiovascular diseases. The positive
      association is only moderate, however remarkably consistent. Periodontal therapy
      can result in positive effects on subclinical markers of atherosclerosis.

PMID- 21887625
TI  - [Significance of dental implants for health care].
AB  - Nowadays, endosseous titanium implants must be considered as an evidence-based
      treatment concept for the replacement of missing teeth. The economic evaluation
      of scientific evidence suggests that patient satisfaction and oral health-related
      quality of life may be improved by mandibular implant-retained overdentures over
      conventional dentures. However, despite promising survival rates reported for
      dental implants, an increase in the prevalence of peri-implant diseases is
      emerging. Accordingly, concepts for quality management in education, research,
      and practice are essential to further improve medical care in implant dentistry.

PMID- 21887626
TI  - [Change and innovation in orthodontics].
AB  - Long-term prophylaxis achievements, demographic changes, scientific progress,
      patient requirements, and political regulations through social legislation will
      fundamentally change the future of orthodontics, i.e., a reduction in children
      and adolescent therapy as well as an increase in interdisciplinary complex
      treatments for adult patients mostly outside the social security system. Health
      care research at a high evidence level needs to be intensified due to social
      political reasons. In addition to well-proven appliances, modern sometimes even
      invisible appliances (CAD-CAM) will be used in future orthodontic therapy. Three
      dimensional diagnostics could improve treatment planning. Whether improved
      prenatal diagnosis will alter the number of newborns with dentofacial
      malformations (cleft lip and palate) or syndromes (e.g., Down syndrome), thus,
      changing treatment needs in the future, cannot be predicted today, due to the
      multiple influencing factors. A well-structured 4-year specialist training
      according to European guidelines will also be necessary in the future to comply
      with complex treatment needs be it within or outside the social security system
      (quality assurance).

PMID- 21887627
TI  - [MRSA bloodstream infections in hospitals in Frankfurt/Main, Germany, 2010 :
      Results of the mandatory notification and suggestions for improvement].
AB  - Since 1 July 2009 in accordance with the statuary order based on the German law
      for infectious diseases (Infektionsschutzgesetz), MRSA in blood and liquor must
      be notified to the public health authorities. The aim of extension of the
      notification to report is to improve the surveillance of nosocomial infections
      and the prevention of nosocomial MRSA infections. In addition to MRSA detection,
      data on symptoms and risk factors, e.g., medical devices, must also be reported.
      In this report, data of bloodstream MRSA infections in hospitals in
      Frankfurt/Main, Germany, for the first complete year (2010)were evaluated. In
      2010, 58 MRSA-positive bloodstream infections were reported by the 17 hospitals
      in Frankfurt to the health protection authorities, i.e., 0.0360 MRSA/1,000
      patient-days (range: 0- 0.109/1,000 patient-days). However, 10 of these
      infections initially had not been reported to the public health department in
      charge for the hospitals, but to the health departments according to the
      patient's addresses. Although most of the infections were reported from large
      hospitals (>100,000 patient-days/year), the highest incidences (0.0416/1,000
      patient-days) were reported from small hospitals (<50,000 patient-days/year). Of
      the blood specimen, 13 (22.4%) were drawn on the first day of hospital stay,
      thus, indicating an imported infection. While 90% of the patients with MRSA in
      the bloodstream suffered from fever, 80% had sepsis and 34.5% suffered from
      pneumonia. Medical devices, such as central venous catheters and PEG, were
      reported from 60% of the patients. In the MRE network Rhine-Main region, the
      public health authorities asked for some more detailed information, such as risk
      factors for MRSA colonization (history for MRSA, recent hospital stay or
      antibiotic therapy, skin disorders, dialysis, residence in a retirements home),
      and for screening results as well as for the MRSA management, i.e., isolation of
      the patient and, if necessary, the contact patient. In 55% of the cases, the
      patients were identified by the clinics themselves as being patients with MRSA
      risk factors, mainly because of a history of MRSA (29%), recent hospital stay
      (71%), and antibiotic therapy during the last 6 months (52%). Screening was
      performed in 31 (53%) of the patients, most of them (71%) with positive MRSA nose
      swab. If the patients were screened, significantly fewer contact patients had to
      be screened and isolated later. Thus, to improve surveillance data on MRSA
      bloodstream infections, the notification route to the public health authorities
      responsible for the clinic hosting the patient must be strictly obeyed in order
      to avoid underreporting und underassessment of nosocomial infection. Although
      asking for clinical symptoms may be useful to validate the result in some cases,
      focus should be placed on risk factors and risk management, including screening
      and isolation. Only then can the aim of improving surveillance and reduction of
      nosocomial MRSA infection be achieved.

PMID- 21887628
TI  - [Public health requirements in punctures and injections].

PMID- 21887633
TI  - Characterization of nitrogen-fixing bacteria isolated from field-grown barley,
      oat, and wheat.
AB  - Diazotrophic bacteria were isolated from the rhizosphere of field-grown Triticum
      aestivum, Hordeum vulgare, and Avena sativa grown in various regions of Greece.
      One isolate, with the highest nitrogen-fixation ability from each of the eleven
      rhizospheres, was selected for further characterisation. Diazotrophic strains
      were assessed for plant-growth-promoting traits such as indoleacetic acid
      production and phosphate solubilisation. The phylogenies of 16S rRNA gene of the
      selected isolates were compared with those based on dnaK and nifH genes. The
      constructed trees indicated that the isolates were members of the species
      Azospirillum brasilense, Azospirillum zeae, and Pseudomonas stutzeri.
      Furthermore, the ipdC gene was detected in all A. brasilence and one A. zeae
      isolates. The work presented here provides the first molecular genetic evidence
      for the presence of culturable nitrogen-fixing P. stutzeri and A. zeae associated
      with field-grown A. sativa and H. vulgare in Greece.

PMID- 21887634
TI  - Bacterial structure and characterization of plant growth promoting and oil
      degrading bacteria from the rhizospheres of mangrove plants.
AB  - Most oil from oceanic spills converges on coastal ecosystems, such as mangrove
      forests, which are threatened with worldwide disappearance. Particular bacteria
      that inhabit the rhizosphere of local plant species can stimulate plant
      development through various mechanisms; it would be advantageous if these would
      also be capable of degrading oil. Such bacteria may be important in the
      preservation or recuperation of mangrove forests impacted by oil spills. This
      study aimed to compare the bacterial structure, isolate and evaluate bacteria
      able to degrade oil and stimulate plant growth, from the rhizospheres of three
      mangrove plant species. These features are particularly important taking into
      account recent policies for mangrove bioreme-diation, implying that oil
      degradation as well as plant maintenance and health are key targets. Fifty-seven
      morphotypes were isolated from the mangrove rhizospheres on Bushneil-Haas (BH)
      medium supplemented with oil as the sole carbon source and tested for plant
      growth promotion. Of this strains, 60% potentially fixed nitrogen, 16% showed
      antimicrobial activity, 84% produced siderophores, 51% had the capacity to
      solubilize phosphate, and 33% produced the indole acetic acid hormone. Using gas
      chromatography, we evaluated the oil-degrading potential of ten selected strains
      that had different morphologies and showed Plant Growth Promoting Rhizobacteria
      (PGPR) features. The ten tested strains showed a promising degradation profile
      for at least one compound present in the oil. Among degrader strains, 46% had
      promising PGPR potential, having at least three of the above capacities. These
      strains might be used as a consortium, allowing the concomitant degradation of
      oil and stimulation of mangrove plant survival and maintenance.

PMID- 21887635
TI  - Polymerase chain reaction-denaturing gradient gel electrophoresis analysis of
      bacterial community structure in the food, intestines, and feces of earthworms.
AB  - The bacterial communities in the food, intestines, and feces of earthworms were
      investigated by PCR-denaturing Gradient gel electrophoresis (DGGE). In this
      study, PCR-DGGE was optimized by testing 6 universal primer sets for microbial
      16S rRNA in 6 pure culture strains of intestinal microbes in earthworms. One
      primer set effectively amplified 16S rRNA from bacterial populations that were
      found in the food, intestines, and feces of earthworms. Compared with the
      reference markers from the pure culture strains, the resulting DGGE profiles
      contained 28 unique DNA fragments. The dominant microorganisms in the food,
      intestines, and feces of earthworms included Rhodobacterales bacterium,
      Fusobacteria, Ferrimonas marina, Aeromonas popoffii, and soil bacteria. Other
      straisn, such as Acinetobacter, Clostridium, and Veillonella, as well as rumen
      bacteria and uncultured bacteria also were present. These results demonstrated
      that PCR-DGGE analysis can be used to elucidate bacterial diversity and identify
      unculturable microorganisms.

PMID- 21887636
TI  - Symbiotic interaction of endophytic bacteria with arbuscular mycorrhizal fungi
      and its antagonistic effect on Ganoderma boninense.
AB  - Endophytic bacteria (Pseudomonas aeruginosa UPMP3 and Burkholderia cepacia
      UMPB3), isolated from within roots of oil palm (Elaeis guineensis Jacq.) were
      tested for their presymbiotic effects on two arbuscular mcorrhizal fungi, Glomus
      intraradices UT126 and Glomus clarum BR152B). These endophytic bacteria were also
      tested for antagonistic effects on Ganoderma boninense PER 71, a white wood rot
      fungal pathogen that causes a serious disease in oil palm. Spore germination and
      hyphal length of each arbuscular mycorrhizal fungal (AMF) pairing with endophytic
      bacteria was found to be significantly higher than spores plated in the absence
      of bacteria. Scanning electron microscopy (SEM) showed that the endophytic
      bacteria were scattered, resting or embedded on the surface hyaline layer or on
      the degraded walls of AMF spores, possibly feeding on the outer hyaline spore
      wall. The antagonistic effect of the endophytic bacteria was expressed as severe
      morphological abnormalities in the hyphal structures of G. boninense PER 71. The
      effects of the endophytic bacteria on G. boninense PER 71 hyphal structures were
      observed clearly under SEM. Severe inter-twisting, distortion, lysis and
      shriveling of the hyphal structures were observed. This study found that the
      effect of endophytic bacteria on G. intraradices UT126 and G. clarum BR152B
      resembled that of a mycorrhiza helper bacteria (MHB) association because the
      association significantly promoted AMF spore germination and hyphal length.
      However, the endophytic bacteria were extremely damaging to G. boninense PER 71.

PMID- 21887637
TI  - Methyl coenzyme M reductase (mcrA) gene based phylogenetic analysis of
      methanogens population in Murrah buffaloes (Bubalus bubalis).
AB  - The aim of the present study was to decipher the diversity of methanogens in
      rumen of Murrah buffaloes so that effective strategies can be made in order to
      mitigate methane emission from these methanogens. In the present study diversity
      of rumen methanogens in Murrah buffaloes (Bubalus bubalis) from North India was
      evaluated by using mcr-A gene library obtained from the pooled PCR product from
      four animals and by using MEGA4 software. A total of 104 clones were examined,
      revealing 26 different mcr-A gene sequences or phylotypes. Of the 26 phylotypes,
      16 (64 of 104 clones) were less than 97% similar to any of the cultured strain of
      methanogens. Seven clone sequences were clustered with Methanomicrobium mobile
      and three clone sequences were clustered with Methanobrevibacter gottschalkii
      during the phylogenetic analysis. Uncultured group of methanogens comes out to be
      the major component of the methanogens community structure in Murrah buffaloes.
      Methanomicrobium phylotype comes out to be major phylotype among cultured
      methanogens followed by Methanobrevibacter phylotype. These results help in
      making effective strategies to check the growth of dominant communities in the
      rumen of this animal which in turn help in the reduction of methane emission in
      the environment and ultimately helps us in fighting with the problem of global
      warming.

PMID- 21887638
TI  - Isolation and evaluation of terrestrial fungi with algicidal ability from Zijin
      Mountain, Nanjing, China.
AB  - Approximately 60 fungal isolates from Zijin Mountain (Nanjing, China) were
      screened to determine their algicidal ability. The results show that 8 fungi
      belonging to Ascomycota and 5 belonging to Basidiomycota have algicidal ability.
      Of these fungi, Irpex lacteus T2b, Trametes hirsuta T24, Trametes versicolor
      F21a, and Bjerkandera adusta T1 showed strong algicidal ability. The order of
      fungal chlorophyll-a removal efficiency was as follows: T. versicolor F21a > I.
      lacteus T2b > B. adusta T1 > T. hirsuta T24. In particular, T. versicolor F21a
      completely removed algal cells within 30 h, showing the strongest algicidal
      ability. The results also show that all 4 fungal species degraded algal cells
      through direct attack. In addition, most of the tested fungi from the order
      Polyporales of Basidiomycota exhibited strong algicidal activity, suggesting that
      most fungi that belong to this order have algicidal ability. The findings of this
      work could direct the search for terrestrial fungi for bloom control.

PMID- 21887639
TI  - Isolation and analyses of uranium tolerant Serratia marcescens strains and their
      utilization for aerobic uranium U(VI) bioadsorption.
AB  - Enrichment-based methods targeted at uranium-tolerant populations among the
      culturable, aerobic, chemo-heterotrophic bacteria from the subsurface soils of
      Domiasiat (India's largest sandstone-type uranium deposits, containing an average
      ore grade of 0.1 % U(3)O(8)), indicated a wide occurrence of Serratia marcescens.
      Five representative S. marcescens isolates were characterized by a polyphasic
      taxonomic approach. The phylogenetic analyses of 16S rRNA gene sequences showed
      their relatedness to S. marcescens ATCC 13880 (>=99.4% similarity). Biochemical
      characteristics and random amplified polymorphic DNA profiles revealed
      significant differences among the representative isolates and the type strain as
      well. The minimum inhibitory concentration for uranium U(VI) exhibited by these
      natural isolates was found to range from 3.5-4.0 mM. On evaluation for their
      uranyl adsorption properties, it was found that all these isolates were able to
      remove nearly 90-92% (21-22 mg/L) and 60-70% (285-335 mg/L) of U(VI) on being
      challenged with 100 MUM (23.8 mg/L) and 2 mM (476 mg/L) uranyl nitrate solutions,
      respectively, at pH 3.5 within 10 min of exposure. his capacity was retained by
      the isolates even after 24 h of incubation. Viability tests confirmed the
      tolerance of these isolates to toxic concentrations of soluble uranium U(VI) at
      pH 3.5. This is among the first studies to report uranium-tolerant aerobic
      chemoheterotrophs obtained from the pristine uranium ore-bearing site of
      Domiasiat.

PMID- 21887640
TI  - Isolation and characterization of ethylbenzene degrading Pseudomonas putida E41.
AB  - Pseudomonas putida E41 was isolated from oil-contaminated soil and showed its
      ability to grow on ethyl-benzene as the sole carbon and energy source. Moreover,
      P. putida E41 show the activity of biodegradation of ethylbenzene in the batch
      culture. E41 showed high efficiency of biodegradation of ethylbenzene with the
      optimum conditions (a cell concentration of 0.1 g wet cell weight/L, pH 7.0, 25
      degrees C, and ethylbenzene concentration of 50 mg/L) from the results of the
      batch culture. The maximum degradation rate and specific growth rate (MU(max))
      under the optimum conditions were 0.19+0.03 mg/mg-DCW (Dry Cell Weight)/h and
      0.87+0.13 h(-1), respectively. Benzene, toluene and ethylbenzene were degraded
      when these compounds were provided together; however, xylene isomers persisted
      during degradation by P. putida E41. When using a bioreactor batch system with a
      binary culture with P. putida BJ10, which was isolated previously in our lab, the
      degradation rate for benzene and toluene was improved in BTE mixed medium (each
      initial concentration: 50 mg/L). Almost all of the BTE was degraded within 4 h
      and 70-80% of m-, p-, and o-xylenes within 11 h in a BTEX mixture (initial
      concentration: 50 mg/L each). In summary, we found a valuable new strain of P.
      putida, determined the optimal degradation conditions for this isolate and tested
      a mixed culture of E41 and BJ10 for its ability to degrade a common sample of
      mixed contaminants containing benzene, toluene, and xylene.

PMID- 21887642
TI  - Characterization of antibiotic resistance determinants in oral biofilms.
AB  - Oral biofilms contain numerous antibiotic resistance determinants that can be
      transferred within or outside of the oral cavity. The aim of this study was to
      evaluate the prevalence and the relative level of antibiotic resistance
      determinants from oral biofilms. Oral biofilm samples that were collected from
      healthy subjects and periodontitis patients were subjected to qualitative and
      quantitative analyses for selected antibiotic resistance determinants using PCR.
      The prevalence of tet(Q), tet(M), cfxA, and bla ( TEM ) was very high both in the
      patient and the healthy subject group, with a tendency toward higher values in
      the patient group, with the exception of erm(F), which was more prevalent in the
      healthy group. The two extended spectrum beta-lactam (ESBL) resistance
      determinants bla ( SHV ) and bla ( TEM ) showed a dramatic difference, as bla (
      TEM ) was present in all of the samples and bla ( SHV ) was not found at all. The
      aacA-aphD, vanA, and mecA genes were rarely detected, suggesting that they are
      not common in oral bacteria. A quantitative PCR analysis showed that the relative
      amount of resistance determinants present in oral biofilms of the patient group
      was much greater than that of the healthy group, exhibiting 17-, 13-, 145-, and 3
      fold increases for tet(Q), tet(M), erm(F), and cfxA, respectively. The results of
      this study suggest that the oral antibiotic resistome is more diverse and
      abundant in periodontitis patients than in healthy subjects, suggesting that
      there is a difference in the diversity and distribution of antibiotic resistance
      in oral biofilms associated with health and disease.

PMID- 21887643
TI  - Cyclic lipopeptide profile of three Bacillus subtilis strains; antagonists of
      Fusarium head blight.
AB  - The objective of the study was to identify the lipopetides associated with three
      Bacillus subtilis strains. The strains are antagonists of Gibberella zeae, and
      have been shown to be effective in reducing Fusarium head blight in wheat. The
      lipopeptide profile of three B. subtilis strains (AS43.3, AS43.4, and OH131.1)
      was determined using mass spectroscopy. Strains AS43.3 and AS43.4 produced the
      anti-fungal lipopeptides from the iturin and fengycin family during the
      stationary growth phase. All three strains produced the lipopeptide surfactin at
      different growth times. Strain OH131.1 only produced surfactin under these
      conditions. The antifungal activity of the culture supernatant and individual
      lipopeptides was determined by the inhibition of G. zeae. Cell-free supernatant
      from strains AS43.3 and AS43.4 demonstrated strong antibiosis of G. zeae, while
      strain OH131.1 had no antibiosis activity. These results suggest a different
      mechanism of antagonism for strain OH131.1, relative to AS43.3 and AS43.4.

PMID- 21887644
TI  - Sphingomonas rosea sp. nov. and Sphingomonas swuensis sp. nov., rosy colored beta
      glucosidase-producing bacteria isolated from soil.
AB  - Two strains PB196(T) and PB62(T) of Gram-negative, non-motile, and non-spore
      forming bacteria, were isolated from soil in South Korea and characterized to
      determine their taxonomic positions. 16S rRNA gene sequence analysis showed that
      the two strains belonged to the genus Sphingomonas. The highest degree of
      sequence similarity of strain PB196(T) was found with PB62(T) (98.9%),
      Sphingomonas humi PB323(T) (98.9%), Sphingomonas kaistensis PB56(T) (98.2%), and
      Sphingomonas astaxanthinifaciens TDMA-17(T) (98.0%). The highest degree of
      sequence similarity of strain PB62(T) was found with Sphingomonas humi PB323(T)
      (98.8%), Sphingomonas astaxanthinifaciens TDMA-17(T) (98.2%), and Sphingomonas
      kaistensis PB56(T) (98.1%). Chemotaxonomic data revealed that they possessed
      ubiquinone-10 (Q-10) as common in the genus Sphingomonas, that the predominant
      fatty acids were summed feature 7 (C(18:1) omega7c/omega9t/omega12t), summed
      feature 4 (C(16:1) omega7c/C(15:0) iso 2OH), C(16:0), and C(17:1) omega6c, and
      that they contained sphingoglycolipid, phosphatidylglycerol (PG), and
      phosphatidyle-thanolamine (PE) in common but they showed difference for
      diphosphatidylglycerol (DPG). Based on these data, PB196(T) (=KCTC 12339(T) =JCM
      16604(T)) and PB62(T) (=KCTC 12336(T) =JCM 16605(T) =KEMB 9004-005(T)) should be
      classified as type strains of two novel species, for which the names Sphingomonas
      rosea sp. nov. and Sphingomonas swuensis sp. nov. are proposed, respectively.

PMID- 21887645
TI  - Paenibacillus telluris sp. nov., a novel phosphate-solubilizing bacterium
      isolated from soil.
AB  - A phosphate-solubilizing bacterial strain designated PS38(T) was isolated from
      farm soil. The isolate was a Gram-positive, motile, endospore-forming, rod-shaped
      bacterium. It grew optimally at 37 degrees C and pH 7.5. The predominant cellular
      fatty acids were anteiso-C(15:0), anteiso-C(17:0), and iso-C(16:0). The DNA G+C
      content was 49.5 mol% and the predominant menaquinone was MK-7. Phylogenese
      analyses based on 16S rRNA gene sequences showed that the strain PS38(T) belonged
      to the genus Paenibacillus and was most closely related to Paenibacillus
      chibensis JCM 9905(T), P. barengoltzii SAFN-016(T), P. timonensis 2301032(T), and
      P. motobuensis MC10(T) with 96.3%, 96.0%, 95.9%, and 95.5% 16S rRNA gene sequence
      similarity, respectively. On the basis of morphological, chemotaxonomic,
      physiological, and phylogenetic properties, strain PS38(T) represents a novel
      species of the genus Paenibacillus, for which the name Paenibacillus telluris sp.
      nov. is proposed. The type strain is PS38(T) (=KCTC 13946(T) =CGMCC 1.10695(T)).

PMID- 21887646
TI  - Identification of enriched conjugated linoleic acid isomers in cultures of
      ruminal microorganisms after dosing with 1-(13)C-linoleic acid.
AB  - Most studies of linoleic acid biohydrogenation propose that it converts to
      stearic acid through the production of cis-9 trans-11 CLA and trans-11 C18:1.
      However, several other CLA have been identified in ruminai contents, suggesting
      additional pathways may exist. To explore this possibility, this research
      investigated the linoleic acid biohydrogenation pathway to identify CLA isomers
      in cultures of ruminai microorganisms after dosing with a (13)C stable isotope.
      The (13)C enrichment was calculated as [(M+1/M)*100] in labeled minus unlabeled
      cultures. After 48 h incubation, significant (13)C enrichment was observed in
      seven CLA isomers, indicating their formation from linoleic acid. All enriched
      CLA isomers had double bonds in either the 9,11 or 10,12 position except for
      trans-9 cis-11 CLA. The cis-9 trans-11 CLA exhibited the highest enrichment
      (30.65%), followed by enrichments from 21.06 to 23.08% for trans-10 cis-12, cis
      10 trans-12, trans-9 trans-11, and trans-10 trans-12 CLA. The remaining two CLA
      (cis-9 cis-11 and cis-10 cis-12 CLA) exhibited enrichments of 18.38 and 19.29%,
      respectively. The results of this study verified the formation of cis-9 trans-11
      and trans-10 cis-12 CLA isomers from linoleic acid biohydrogenation. An
      additional five CLA isomers also contained carbons originating from linoleic
      acid, indicating that pathways of linoleic acid biohydrogenation are more complex
      than previously described.

PMID- 21887641
TI  - Microbial community analysis and identification of alternative host-specific
      fecal indicators in fecal and river water samples using pyrosequencing.
AB  - It is important to know the comprehensive microbial communities of fecal
      pollution sources and receiving water bodies for microbial source tracking.
      Pyrosequencing targeting the V1-V3 hypervariable regions of the 16S rRNA gene was
      used to investigate the characteristics of bacterial and Bacteroidales
      communities in major fecal sources and river waters. Diversity analysis indicated
      that cow feces had the highest diversities in the bacterial and Bacteroidales
      group followed by the pig sample, with human feces having the lowest value. The
      Bacteroidales, one of the potential fecal indicators, totally dominated in the
      fecal samples accounting for 31%-52% of bacterial sequences, but much less (0.6%)
      in the river water. Clustering and Venn diagram analyses showed that the human
      sample had a greater similarity to the pig sample in the bacterial and
      Bacteroidales communities than to samples from other hosts. Traditional fecal
      indicators, i.e., Escherichia coli, were detected in the human and river water
      samples at very low rates and Clostridium perfringens and enterococci were not
      detected in any samples. Besides the Bacteroidales group, some microorganisms
      detected in the specific hosts, i.e., Parasutterella excrementihominis,
      Veillonella sp., Dialister invisus, Megamonas funiformis, and Ruminococcus
      lactaris for the human and Lactobacillus amylovorus and Atopostipes sp. for the
      pig, could be used as potential host-specific fecal indicators. These
      microorganisms could be used as multiple fecal indicators that are not dependent
      on the absence or presence of a single indicator. Monitoring for multiple
      indicators that are highly abundant and host-specific would greatly enhance the
      effectiveness of fecal pollution source tracking.

PMID- 21887647
TI  - Identification of an extracellular thermostable glycosyl hydrolase family 13
      alpha-amylase from Thermotoga neapolitana.
AB  - We cloned the gene for an extracellular alpha-amylase, AmyE, from the
      hyperthermophilic bacterium Thermotoga neapolitana and expressed it in
      Escherichia coli. The molecular mass of the enzyme was 92 kDa as a monomer.
      Maximum activity was observed at pH 6.5 and temperature 75 degrees C and the
      enzyme was highly thermostable. AmyE hydrolyzed the typical substrates for alpha
      amylase, including soluble starch, amylopectin, and maltooli-gosaccharides. The
      hydrolytic pattern of AmyE was similar to that of a typical alpha-amylase;
      however, unlike most of the calcium (Ca(2+))-dependent alpha-amylases, the
      activity of AmyE was unaffected by Ca(2+). The specific activities of AmyE
      towards various substrates indicated that the enzyme preferred
      maltooligosaccharides which have more than four glucose residues. AmyE could not
      hydrolyze maltose and maltotriose. When maltoheptaose was incubated with AmyE at
      the various time courses, the products consisting of maltose through
      maltopentaose was evenly formed indicating that the enzyme acts in an endo
      fashion. The specific activity of AmyE (7.4 U/mg at 75 degrees  C, pH 6.5, with
      starch as the substrate) was extremely lower than that of other extracellular
      alpha-amylases, which indicates that AmyE may cooperate with other highly active
      extracellular alpha-amylases for the breakdown of the starch or alpha-glucans
      into maltose and maltotriose before transport into the cell in the members of
      Thermotoga sp.

PMID- 21887648
TI  - Transcriptional and biochemical characterization of two Azotobacter vinelandii
      FKBP family members.
AB  - Peptidyl-prolyl cis/trans isomerases (PPIases, EC: 5.2.1.8), a class of enzymes
      that catalyse the rate-limiting step of the cis/trans isomerization in protein
      folding, are divided into three structurally unrelated families: cyclophilins,
      FK506-binding proteins (FKBPs), and parvulins. Two recombinant FKBPs from the
      soil nitrogen-fixing bacterium Azotobacter vinelandii, designated as AvfkbX and
      AvfkbB, have been purified and their peptidyl-prolyl cis/trans isomerase activity
      against Suc-Ala-Xaa-Pro-Phe-pNA synthetic peptides characterised. The substrate
      specificity of both enzymes is typical for bacterial FKBPs, with Suc-Ala-Phe-Pro
      Phe-pNA being the most rapidly catalysed substrate by AvfkbX and Suc-Ala-Leu-Pro
      Phe-pNA by AvfkbB. Both FKBPs display chaperone activity as well in the citrate
      synthase thermal aggregation assay. Furthermore, using real-time RT-qPCR, we
      demonstrated that both genes were expressed during the exponential growth phase
      on glucose minimal medium, while their expression declined dramatically during
      the stationary growth phase as well as when the growth medium was supplied
      exogenously with ammonium.

PMID- 21887649
TI  - The ATPase activity of the G2alt gene encoding an aluminium tolerance protein
      from Anoxybacillus gonensis G2.
AB  - The G2ALT gene was cloned and sequenced from the thermophilic bacterium
      Anoxybacillus gonensis G2. The gene is 666 bp long and encodes a protein 221
      amino acids in length. The gene was overexpressed in E. coli and purified to
      homogeneity and biochemically characterized. The enzyme has a molecular mass of
      24.5 kDa and it could be classified as a member of the family of bacterial
      aluminium resistance proteins based on homology searches. When this fragment was
      expressed in E. coli, it endowed E. coli with Al tolerance to 500 MUM. The
      purified G2ALT protein is active at a broad pH range (pH 4.0-10.0) and
      temperature range (25 degrees C-80 degrees C) with optima of 6.0 and the apparent
      optimal temperature of 73 degrees C respectively. Under optimal conditions, G2ALT
      exhibited a low ATPase activity with K (m) (-) and V (max) (-) values of 10+/
      0.55 MUM and 26.81+/-0.13 mg Pi released/min/mg enzyme, respectively. The ATPase
      activity of G2ALT requires Mg(2+) and Na(+) ions, while Zn(2+) and Al(3+)
      stimulate the activity. Cd(2+) and Ag(+) reduced the activity and Li(+), Cu(2+),
      and Co(2+) inhibited the activity. Known inhibitors of most ATPases, like such as
      beta-mercaptoethanol and ouabain, also inhibited the activity of the G2ALT. These
      biochemical characterizations suggested that G2ALT belongs to the PP-loop ATPase
      superfamily and it can be responsible for aluminium tolerance in A. gonensis G2.

PMID- 21887650
TI  - Macrolide resistance and in vitro selection of resistance to antibiotics in
      Lactobacillus isolates.
AB  - Spreading of resistance to antibiotics is of great concern due to the increasing
      rate of isolation of multiresistant pathogens. Since commensal bacteria may
      transfer determinants of resistance to pathogens, studies on development of
      resistance should include also lactobacilli. Resistance to macrolides,
      penicillins and tetracycline was determined in 40 isolates of Lactobacillus
      acidophilus, Lactobacillus plantarum, Lactobacillus crispatus, and Lactobacillus
      casei isolated from faeces of apparently healthy volunteers. Frequency of
      mutation and changes in susceptibility after serial exposure to these antibiotics
      at concentrations of 4* and 8* MIC were evaluated in susceptible isolates.
      Acquired resistance was defined as an increment in MIC values of at least four
      times in respect to the pre-selection values. Resistance to macrolides and/or
      tetracycline was identified in 14 and 4 isolates, respectively. ermB gene and
      A2058G mutation in 23S rRNA were detected in macrolide resistant isolates.
      Frequencies of mutation of susceptible isolates (n=26) were lower for ampicillin
      and erythromycin than for tetracycline. Serial exposure to antibiotics led to
      selection of resistant mutants. However, acquired resistance was rather unstable
      and was lost after subcultures in antibiotic-free medium in most mutants.
      Resistance to erythromycin was associated to a A2058G mutation in 23S rRNA. In
      conclusion, results indicate that resistance to macrolides and tetracycline is
      present among intestinal lactobacilli. Decrease in susceptibility following
      serial exposure to antibiotics might occur in lactobacilli, in a strain- and
      antibiotic-dependent way. Since lactobacilli are often used as probiotics, their
      ability to acquire resistance should be evaluated for isolates candidate to be
      included in probiotics based products.

PMID- 21887651
TI  - Food-borne enterococci and their resistance to oxidative stress.
AB  - Enterococci are important food-borne pathogens that cause serious infections.
      Several virulence factors have been described including aggregation substance,
      gelatinase, cytolysin, and enterococcal surface protein. The ability to cause
      infections is mainly dependent on the response to oxidative stress due to the
      production of reactive oxygen species by immune cells. The aim of our study was
      to analyze the resistance of enterococcal strains from food to clinically
      relevant antiseptic agents with regard to the presence of selected virulence
      factors, and to uncover potential mechanisms of the antioxidative resistance.
      Eighty-two enterococcal isolates from Bryndza cheese were tested using in vitro
      growth assays to study the ability of these isolates to survive exposure to
      antiseptic agents - hydrogen peroxide, hypochlorite, and Chlorhexidine. Virulence
      genotypes of the isolates were determined by PCR, and RT real time PCR was used
      for gene expression under oxidative stress. Resistance against antiseptic agents
      depends on the concentration of applied chemicals, on the time of exposure, but
      also on virulence factors of the enterococcal strains. Oxidative stress induces
      the expression of antioxidative enzymes and down-regulates the expression of
      prooxidative enzymes. These effects are dependent on the virulence genotype of
      the enterococcal strains. These findings are important for future research,
      especially concerning the role of enterococci in oral diseases.

PMID- 21887652
TI  - The activity of a small lytic peptide PTP-7 on Staphylococcus aureus biofilms.
AB  - One of the most important features of bacterial biofilms is their resistance to
      antibiotics and to the host immune system. In this study, we have found that a
      small lytic peptide, PTP-7, is very potent to Gram-positive bacteria and is able
      to kill antibiotic sensitive and resistant Staphylococcus aureus
      indiscriminately. Further studies have revealed that despite being a cationic
      peptide, the antibacterial activity of PTP-7 was not affected by the negatively
      charged extracellular polymeric substance (EPS) of biofilms. PTP-7 could diffuse
      into the deep layer of S. aureus biofilms to kill bacteria inside biofilms
      efficiently and effectively. Neither the high concentrations of metal ions nor
      the acidic pH in biofilms affected the activity of peptide PTP-7. It seems that
      the unique sequence/structure together with the resistant bacteria killing
      ability of peptide PTP-7 confers its anti-biofilm activity. This study sheds new
      light on the treatment of bacterial biofilms, especially various biofilm related
      infections.

PMID- 21887653
TI  - Taxonomy of Eurotium species isolated from meju.
AB  - Eurotium strains were isolated from 77 loaves of meju (dried fermented soybeans),
      in various regions of Korea from 2008 to 2010. Morphological characteristics and
      DNA sequences of beta-tubulin were examined. They were identified as Eurotium
      amstelodami, E. chevalieri, E. herbariorum, E. repens, E. rubrum, and E.
      tonophilum. Of these species, E. chevalieri and E. tonophilum had not been
      previously reported in association with meju. E. chevalieri and E. repens were
      the species isolated most frequently. This paper summarizes the morphological
      characteristics of six Eurotium species and provides key to identify the species
      from meju.

PMID- 21887654
TI  - A rapid PCR-based approach for molecular identification of filamentous fungi.
AB  - In this study, a novel rapid and efficient DNA extraction method based on
      alkaline lysis, which can deal with a large number of filamentous fungal isolates
      in the same batch, was established. The filamentous fungal genomic DNA required
      only 20 min to prepare and can be directly used as a template for PCR
      amplification. The amplified internal transcribed spacer regions were easy to
      identify by analysis. The extracted DNA also can be used to amplify other protein
      coding genes for fungal identification. This method can be used for rapid
      systematic identification of filamentous fungal isolates.

PMID- 21887655
TI  - Characterization of a mutant strain of a filamentous fungus Cladosporium phlei
      for the mass production of the secondary metabolite phleichrome.
AB  - UV-mutagenesis was performed to obtain mutant strains that demonstrate altered
      production of phleichrome, a secondary metabolite of Cladosporium phlei. Among
      fifty mutants selected, based on the increased area and intensity of the purple
      pigment surrounding the colonies, the strain M0035 showed the highest production
      of phleichrome, more than seven fold over wild type. Plate cultures of the M0035
      strain resulted in a total of 592 mg phleichrome consisting of 146 mg and 446 mg
      from the mycelia and agar media, respectively. The M0035 strain displayed a
      growth rate and a mycelial mass comparable to the parental strain but had
      significantly reduced asexual sporulation.

PMID- 21887656
TI  - Complete sequence and organization of the Sphingobium chungbukense DJ77 pSY2
      plasmid.
AB  - Sphingobium chungbukense DJ77 is capable of metabolizing priority chemicals of
      human health concern such as polycyclic aromatic hydrocarbons (PAHs),
      extracellular polysaccharide (EPS), and antibiotics. Here, we report the complete
      DNA and genetic organization of the plasmid pSY2 from strain DJ77. A DNA sequence
      analysis revealed that pSY2 comprises 18,779 bp encoding 22 open reading frames
      (ORFs) with 59.5% G+C content. The ORFs on pSY2 were classified into DNA
      replication, conjugative function, transposition, plasmid stability/partition,
      and other functional groups (transport, fatty acid biosynthesis, stress, and
      growth rate regulation). Three ORFs on pSY2 were hypothetical proteins.

PMID- 21887657
TI  - rRNASelector: a computer program for selecting ribosomal RNA encoding sequences
      from metagenomic and metatranscriptomic shotgun libraries.
AB  - Metagenomic and metatranscriptomic shotgun sequencing techniques are gaining
      popularity as more cost-effective next-generation sequencing technologies become
      commercially available. The initial stage of bioinfor-matic analysis generally
      involves the identification of phylogenetic markers such as ribosomal RNA genes.
      The sequencing reads that do not code for rRNA can then be used for protein-based
      analysis. Hidden Markov model is a well-known method for pattern recognition.
      Hidden Markov models that are trained on well-curated rRNA sequence databases
      have been successfully used to identify DNA sequence coding for rRNAs in pro
      karyotes. Here, we introduce rRNASelector, which is a computer program for
      selecting rRNA genes from massive metagenomic and metatranscriptomic sequences
      using hidden Markov models. The program successfully identified prokaryotic 5S,
      26S, and 23S rRNA genes from Roche 454 FLX Titanium-based metagenomic and
      metatranscriptomic libraries. The rRNASelector program is available at
      http://sw.ezbiocloud.net/rrnaselector .

PMID- 21887658
TI  - [Our children, our future].

PMID- 21887659
TI  - [Universal newborn hearing screening (UNHS): is it possible to successfully
      implement it nationwide?].
AB  - BACKGROUND: Since 01.01.2009 in Germany a newborn hearing screening (UNHS) is
      obligatory for every child. The UNHS is part of the guidelines for the prevention
      of diseases for children up to 6 years of age (Kinder-Richtlinien). 2 years after
      its introduction in Bavaria, we now evaluate whether the UNHS has been
      implemented successfully,and if the quality criteria of the guidelines have been
      met. METHODS: In the guidelines details for the procedure and screening quality
      are given. The UNHS data from the screening facilities in Bavaria were evaluated
      for process quality criteria like screening coverage, screening method, REFER
      rate (rate of failed tests) and child age at diagnosis. RESULTS: More than 96 %
      of all newborns were screened. The REFER rate for 2010 was 4.5 %. Only 18 % of
      the controls were done by a paediatric audiologist.In 38.5 % of the newborns an
      intervention of the screening centre was necessary to assure controlling of a
      failed screening test. In 2009 the median age at diagnosis for a bilateral
      hearing loss was 5.5 months, and the start of therapy was 6.2 months. CONCLUSION:
      In Bavaria the UNHS was implemented successfully. A tracking system for all
      children who failed the hearing screening test is pivotal for the early diagnosis
      of children with bilateral hearing deficiency.

PMID- 21887661
TI  - Hepatitis E: an emerging infectious disease in Germany?
AB  - Increased frequencies of HEV infections have been reported in several
      industrialized countries. We suggest that this finding might be explained by a
      better awareness of the disease and not by an increased incidence. Although
      reported HEV infections increased more than 6-fold in Germany in recent years,
      the seroprevalence remained unchanged (2 %).

PMID- 21887662
TI  - Ambrisentan improves exercise capacity and symptoms in patients with
      portopulmonary hypertension.
AB  - INTRODUCTION: Ambrisentan, a selective endothelin receptor antagonist has been
      approved in several countries for pulmonary arterial hypertension. No data have
      been published on the efficacy of ambrisentan on improvement of exercise capacity
      in patients with portopulmonary hypertension (PoPH). PATIENTS AND METHODS: We
      retrospectively analyzed the safety and efficacy of ambrisentan in patients with
      PoPH in four German university hospitals. RESULTS: 14 patients with moderate to
      severe PoPH were included. The median follow-up was 16 months (IQR, 12 - 21). 6
      minute walk tests after 6 and 12 months improved from 376 meters (IQR, 207 - 440)
      at baseline to 415 meters (IQR, 393 - 475; p = 0.011) and 413 meters (IQR, 362 -
      473, p = 0.005), respectively. WHO- functional class after 1 year of therapy with
      ambrisentan also improved significantly (p = 0.014). No significant changes in
      blood gas analysis and liver function tests (aspartate aminotransferase, alanine
      aminotransferase, total bilirubin, and international normalized ratio) during
      therapy with ambrisentan were detectable. CONCLUSIONS: The present study
      demonstrates significant improvement of exercise capacity and clinical symptoms
      without relevant safety concerns during ambrisentan treatment in patients with
      PoPH.

PMID- 21887663
TI  - Acute Pancreatitis in a patient with hypercalcemia due to tertiary
      hyperparathyroidism.
AB  - Hypercalcemia represents an independent risk factor of acute pancreatitis and can
      result from hyperfunctioning parathyroid glands. Here, we report on a 35-year-old
      patient who was admitted to our hospital with abdominal pain six weeks after
      kidney transplantation. Based on laboratory tests and ultrasound imaging, acute
      pancreatitis with hypercalcemia due to tertiary hyperparathyroidism was
      diagnosed. Subsequently, the patient was treated by parathyroidectomy with
      autologous tissue transplantation. This constellation points to acute
      pancreatitis as a very rare and severe complication of patients developing
      tertiary hyperparathyroidism-related hypercalcemia from secondary
      hyperparathyroidism after kidney transplantation.

PMID- 21887664
TI  - Weight loss and severe jaundice in a patient with hyperthyroidism.
AB  - BACKGROUND: Thyrotoxicosis may significantly alter hepatic function and is
      associated with autoimmune disorders of the liver. CASE REPORT: We report the
      case of a thyrotoxic patient with Graves' disease and histologically established
      cholestatic hepatitis. Medical treatment of hyperthyroidism normalized liver
      function tests. CONCLUSIONS: In patients with elevated liver function parameters
      and jaundice of unknown origin, thyroid function should generally be tested.
      Moreover, medical treatment of hyperthyroidism with thyrostatics may cause severe
      hepatitis whereas untreated hyperthyroid patients are at risk of developing
      chronic liver failure.

PMID- 21887665
TI  - [Gastric stump carcinoma--a surgical and oncological challenge].
AB  - Gastric stump carcinoma after gastric surgery for benign disease is now widely
      recognized as a distinct clinical entity. An electronic literature search was
      performed in the MEDLINE database to identify relevant studies concerning
      epidemiology, prognosis, treatment, aetiology and pathology of gastric stump
      carcinoma. The references reported in these studies were used to complete the
      literature search. It can be assumed that approximately 10 % of patients who had
      undergone a distal gastric resection for benign disease will develop a carcinoma
      in the gastric remnant about 15 to 20 years after the primary procedure. The
      incidence is reported to be higher in males and following Billroth II resection.
      The site of tumour growth is predominantly in the anastomotic area, but may occur
      anywhere in the stump. Enterogastric reflux, achlorhydria, bacterial overgrowth,
      and genetic factors appear to be the major factors involved in the
      aetiopathogenesis of the gastric stump cancer. Unfortunately, a significant
      proportion of patients presents with synchronous metastases. Clinical symptoms
      are mainly attributed to locally advanced tumour growth. Surgical therapy
      comprises total removal of the gastric remnant and the jejunal segment including
      modified lymphadenectomy (D2 lymphadenectomy and jejunal mesentery). Surveillance
      of patients with endoscopy and multiple biopsies should be initiated from the
      tenth postoperative year and may provide the means to diagnose tumours at an
      early stage.

PMID- 21887666
TI  - [Renaissance of the selective COX-2 inhibitors (coxibes)?].

PMID- 21887667
TI  - [Rifaximin treatment in hepatic encephalopathy].

PMID- 21887669
TI  - [Are neuroleptics neurotoxic?].

PMID- 21887670
TI  - [Mandatory community treatment order - experiences from Wales].

PMID- 21887672
TI  - [Short report on the "Quality in psychiatry and psychotherapy - incentives for a
      sustainable health care system" workshop].

PMID- 21887673
TI  - [Position of executive physicians and medical directors of psychiatry,
      psychotherapy and psychosomatic medicine clinics on the project of integrated
      management of schizophrenic patients by I3G in Lower Saxony].

PMID- 21887674
TI  - Glomerular filtration rate in early diabetes: ongoing discussions of causes and
      mechanisms.
AB  - Glomerular hyperfiltration (>140 ml/min per 1.73 m2 body surface area) is found
      in early diabetes and is associated with a poor prognosis with respect to the
      development of diabetic kidney disease. This review addresses recent
      investigations and discussions of the following hypotheses behind diabetic
      hyperfiltration: Increased proximal tubular volume reabsorption results in a
      pressure drop in Bowman's capsule which increases glomerular filtration rate
      (GFR). Proximal tubular hyperreabsorption induces an increase in GFR mediated by
      tubuloglomerular feedback. Dietary NaCl restriction results in a paradoxically
      increased GFR and increased urine volume in diabetic animals.

PMID- 21887675
TI  - Do HMG-CoA reductase inhibitors improve kidney function? The saga continues.
AB  - Several reviews have addressed the role of dyslipidemia in renal injury and the
      potential renal protective effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG
      CoA) reductase inhibitors (statins). Experimental evidence in animals strongly
      supports the concept that statins may be renal protective. However, data in
      humans are scanty and contradictory. A recent controlled study using rosuvastatin
      has cast some doubts on the renal protective effect of this drug. This article
      reviews the available evidence pro and con the renal protective effects of
      statins in human subjects.

PMID- 21887676
TI  - Incidence of subsequent pancreatic adenocarcinoma in patients with a history of
      nonpancreatic primary cancers.
AB  - BACKGROUND: Several environmental risk factors are known to predispose
      individuals to pancreatic cancer, and up to 15% of pancreatic cancers have an
      inherited component. Understanding metachronous cancer associations can modify
      pancreas cancer risk. The objective of this study was to investigate the
      association of nonpancreatic cancers with subsequent pancreatic adenocarcinoma.
      METHODS: The authors used data from the US Surveillance, Epidemiology, and End
      Results (SEER) registries to identify 1,618,834 individuals who had a primary
      malignancy and subsequent pancreatic adenocarcinoma (n = 4013). Standardized
      incidence ratios were calculated as an approximation of relative risk (RR) for
      the occurrence of pancreatic adenocarcinoma after another primary malignancy.
      RESULTS: Among patients who were diagnosed with a first primary malignancy at
      ages 20 to 49 years, the risk of subsequent pancreatic adenocarcinoma was
      increased among patients who had cancers of the ascending colon (relative risk
      [RR], 4.62; 95% confidence interval [CI], 1.86-9.52), hepatic flexure (RR, 5.42;
      95% CI, 1.12-15.84), biliary system (RR, 13.14; 95% CI, 4.27-30.66), breast (RR,
      1.32; 95% CI, 1.09-1.59), uterine cervix (RR, 1.61; 95% CI, 1.02-2.41), testes
      (RR, 2.78; 95% CI, 1.83-4.05), and hematopoietic system (RR, 1.83; 95% CI, 1.28
      2.53). Among patients who had a first malignancy at ages 50 to 64 years, the risk
      was increased after cancers of the stomach (RR, 1.88; 95% CI, 1.13-2.93), hepatic
      flexure (RR, 2.25; 95% CI, 1.08-4.13), lung and bronchus (RR, 1.46; 95% CI, 1.16
      1.82), pharynx (RR, 2.26; 95% CI, 1.13-4.04), and bladder (RR, 1.24; 95% CI, 1.03
      1.48). Among patients who had a primary cancer after age 65 years, the risk was
      increased after cancers of the stomach (RR, 1.79; 95% CI, 1.23-2.53), hepatic
      flexure (RR, 1.76; 95% CI, 1.06-2.75), biliary system (RR, 2.35; 95% CI, 1.17
      4.20), and uterus (RR, 1.23; 95% CI, 1.03-1.47). CONCLUSIONS: The results from
      the current population-based data set suggested that pancreatic adenocarcinoma is
      associated with certain primary cancers. Genetic predisposition and common
      environmental and behavioral risk factors all may contribute to this observation.
      Specific tumor associations will guide future risk-stratification efforts.

PMID- 21887677
TI  - 18F-fluoro-deoxyglucose positron emission tomography in assessment of myeloma
      related bone disease: a systematic review.
AB  - BACKGROUND: The goal of this study was to conduct a comparative analysis of whole
      body X-ray (WBXR) and (18) F-fluoro-deoxyglucose positron emission tomography
      ((18) FDG PET) in staging and response assessment of multiple myeloma. METHODS:
      We performed a systematic review of studies comparing (18) FDG PET with WBXR
      and/or magnetic resonance imaging in terms of sensitivity for myeloma-related
      bone disease at staging and during follow-up. RESULTS: Eighteen studies involving
      798 patients met the inclusion criteria. The mean Quality Assessment of
      Diagnostic Accuracy Studies (QUADAS) score, expressed as a percentage of the
      maximum score, was 61%. In 7 studies (n = 242 patients), concordance assessment
      between WBXR and (18) FDG PET scan was possible, showing a higher sensitivity of
      the (18) FDG PET in the detection of myeloma bone lesions in 6 studies. The only
      study reporting on the prognostic value of (18) FDG PET at staging found that the
      number of FDG-avid focal lesions was an independent prognostic parameter. In
      addition, the limited studies on response monitoring showed that normalization of
      (18) FDG PET during treatment correlated with a superior clinical outcome.
      CONCLUSIONS: In general, (18) FDG PET has a superior sensitivity for myeloma bone
      lesions compared with WBXR. Future studies have to validate the additive value of
      myeloma-related bone disease detected on (18) FDG PET-computed tomography (CT) in
      predicting outcome. Response monitoring with the use of (18) FDG PET-CT during
      treatment is promising, allowing more precise prediction of prognosis compared
      with the standard response monitoring. In view of the expanding treatment options
      for multiple myeloma, this may provide important information for treatment
      decisions in the future.

PMID- 21887678
TI  - Pretreatment fertility counseling and fertility preservation improve quality of
      life in reproductive age women with cancer.
AB  - BACKGROUND: The post-treatment quality of life (QOL) impacts of receiving
      precancer-treatment infertility counseling and of pursuing fertility preservation
      have not been described in large-scale studies of reproductive age women with
      cancer. METHODS: In total, 1041 women who were diagnosed between ages 18 and 40
      years responded to a retrospective survey and reported whether they received
      infertility counseling before cancer treatment and whether they took action to
      preserve fertility. Five cancer types were included: leukemia, Hodgkin disease,
      non-Hodgkin lymphoma, breast cancer, and gastrointestinal cancer. Validated QOL
      scales were used: the Decision Regret Score, the Satisfaction with Life Scale
      (SWLS), and the brief World Health Organization QOL questionnaire. RESULTS:
      Overall, 560 women (61%) who received treatment that potentially could affect
      fertility were counseled by the oncology team, 45 (5%) were counseled by
      fertility specialists, and 36 (4%) took action to preserve fertility.
      Pretreatment infertility counseling by a fertility specialist and an oncologist
      resulted in lower regret than counseling by an oncologist alone (8.4 vs 11.0; P <
      .0001). The addition of fertility preservation (6.6 vs 11.0; P < .0001) also was
      associated with even lower regret scores than counseling by an oncologist alone.
      Further improvements also were observed in SWLS scores with the addition of
      fertility specialist counseling (23.0 vs 19.8; P = .09) or preserving fertility
      (24.0 vs 19.0; P = .05). CONCLUSIONS: Receiving specialized counseling about
      reproductive loss and pursuing fertility preservation is associated with less
      regret and greater QOL for survivors, yet few patients are exposed to this
      potential benefit. Women of reproductive age should have expert counseling and
      should be given the opportunity to make active decisions about preserving
      fertility.

PMID- 21887679
TI  - A phase 2 randomized multicenter study of 2 extended dosing schedules of oral
      ezatiostat in low to intermediate-1 risk myelodysplastic syndrome.
AB  - BACKGROUND: Ezatiostat is a glutathione analog prodrug glutathione S-transferase
      P1-1 (GSTP1-1) inhibitor. This study evaluated 2 extended dose schedules of oral
      ezatiostat in 89 heavily pretreated patients with low to intermediate-1 risk
      myelodysplastic syndrome (MDS). METHODS: Patients were randomized by 1
      stratification factor-baseline cytopenia (anemia only vs anemia with additional
      cytopenias)-to 1 of 2 extended dosing schedules. Multilineage hematologic
      improvement (HI) responses were assessed by International Working Group 2006
      criteria. RESULTS: Overall, 11 of 38 (29%) red blood cell (RBC) transfusion
      dependent patients had HI-Erythroid (HI-E) response. The median duration of HI-E
      response was 34 weeks. Multilineage responses were observed. There was 1
      cytogenetic complete response in a del (5q) MDS patient. An important trend was
      the effect of prior therapy on response. A 40% HI-E rate (6 of 15 patients) was
      observed in patients who had prior lenalidomide and no prior hypomethylating
      agents (HMAs), with 5 of 11 (45%) patients achieving significant RBC transfusion
      reduction and 3 of 11 (27%) achieving transfusion independence. A 28% HI-E rate
      (5 of 18 patients) was observed in patients who were both lenalidomide and HMA
      naive, with 4 of 8 (50%) patients achieving clinically significant RBC
      transfusion reductions. Most common ezatiostat-related adverse events were grade
      1 and 2 gastrointestinal including: nausea (45%, 17%), diarrhea (26%, 7%), and
      vomiting (30%, 12%). CONCLUSIONS: Ezatiostat is the first GSTP1-1 inhibitor shown
      to cause clinically significant and sustained reduction in RBC transfusions,
      transfusion independence, and multilineage responses in MDS patients. The
      tolerability and activity profile of ezatiostat may offer a new treatment option
      for patients with MDS.

PMID- 21887680
TI  - Germline genetic polymorphisms may influence chemotherapy response and disease
      outcome in osteosarcoma: a pilot study.
AB  - BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and
      young people. Efficacy of multiagent MAP (methotrexate, doxorubicin [Adriamycin],
      cisplatin) chemotherapy may be influenced by multiple cellular pathways. This
      pilot study aimed to investigate the association of 36 candidate genetic
      polymorphisms in MAP pathway genes with histological response, survival, and
      grade 3-4 chemotherapy toxicity in osteosarcoma. METHODS: Blood samples were
      obtained from 60 patients who had completed MAP chemotherapy. All patients were
      manually genotyped for 5 polymorphisms. The remaining 31 polymorphisms were
      genotyped in 50 patients using the Illumina 610-Quad microarray. Associations
      between candidate polymorphisms and histological response, progression-free
      survival, and toxicity were estimated using Pearson chi-square and Fisher exact
      tests, the Kaplan-Meier method, the log-rank test, and the Cox proportional
      hazards model. RESULTS: Poor histological response was increased in variants of
      ABCC2 c.24C>T (P = .011) and GSTP1 c.313A>G p.Ile(105)Val (P = .009), whereas
      MTHFD1 c.1958G>A p.Arg(653)Gln was protective (P = .03). Methotrexate toxicity
      was increased in variants of MTHFR c.1298A>C p.Glu(429)Ala (P = .038), ABCB1
      c.3435T>C Ile(145)Ile (P = .027), and ABCC2 c.3563T>A p.Val(1188)Glu (P = .028).
      Variants of GSTP1 c.313A>G p.Ile(105)Val were at increased risk of
      myelosuppression (P = .024) and cardiac damage (P = .008). CONCLUSIONS: This
      pilot study represents the most comprehensive study to date examining the role of
      genetic polymorphisms in osteosarcoma. Although small and retrospective, it shows
      that several polymorphisms appear to significantly influence toxicity and
      clinical outcome. These deserve prospective validation in the hope of optimizing
      treatment for resistant disease and reducing the late effects burden.

PMID- 21887681
TI  - Adjuvant trastuzumab reduces locoregional recurrence in women who receive breast
      conservation therapy for lymph node-negative, human epidermal growth factor
      receptor 2-positive breast cancer.
AB  - BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)
      positive breast cancer have a higher risk of locoregional recurrence (LRR), even
      in the setting of early stage, lymph node-negative disease. In this sequential,
      retrospective study, the authors evaluated whether adjuvant trastuzumab was
      associated with reduced LRR in women with lymph node-negative, HER2-positive
      disease who received breast-conservation therapy (BCT). METHODS: By using an
      institutional database, 197 women were identified who had lymph node-negative,
      HER2-positive breast cancer measuring <=5 cm diagnosed between 2002 and 2008 and
      who received BCT, including whole-breast irradiation. Two cohorts were compared:
      70 women who did not receive trastuzumab (the no-trastuzumab cohort) and 102
      women who did receive trastuzumab (the trastuzumab cohort). Kaplan-Meier methods
      were used to estimate LRR-free survival. RESULTS: The 2 cohorts were similar in
      age, tumor size, histology, and hormone receptor status. Chemotherapy was
      received by 73% of the no-trastuzumab cohort and by 100% of the trastuzumab
      cohort. In both groups, 99% of patients completed radiotherapy with a median dose
      of 60 Gray. The median recurrence-free follow-up was 86 months for the no
      trastuzumab cohort and 47 months for the trastuzumab cohort. The 3-year LRR-free
      survival rate was 90% (95% confidence interval, 83%-97%) for the no-trastuzumab
      cohort and 99% (95% confidence interval, 97%-100%) for the trastuzumab cohort. In
      the no-trastuzumab cohort, LRR occurred in 7 patients (median time to LRR, 14
      months). In the trastuzumab cohort, there was 1 LRR at 14 months. CONCLUSIONS:
      Even among women with lower risk breast cancer, the relatively high locoregional
      failure rates associated with positive HER2 status could be reduced markedly with
      adjuvant trastuzumab chemotherapy. Within 3 years, a 10% LRR rate without
      trastuzumab and a 1% LRR rate with trastuzumab were observed in women with lymph
      node-negative disease who received BCT.

PMID- 21887682
TI  - Functional regulatory variants of MCL1 contribute to enhanced promoter activity
      and reduced risk of lung cancer in nonsmokers: implications for context-dependent
      phenotype of an antiapoptotic and antiproliferative gene in solid tumor.
AB  - BACKGROUND: Dysfunction of molecules that regulate both apoptosis and
      proliferation is involved in tumorigenesis. A common insertional polymorphism in
      promoter of MCL1, a member of BCL2 family gene with the dual regulatory
      functions, has been shown to be functional in leukemia, but its association with
      cancer predisposition and prognosis has not been well established. We
      hypothesized that MCL1 promoter variants may modify risk of solid cancer.
      METHODS: We genotyped -190 insertional polymorphism and 3 linked single
      nucleotide polymorphisms (SNPs) (-627A>C, -298G>C, and -235C>A) in 320 lung
      cancer patients and 362 controls, and analyzed their functional significance.
      RESULTS: We confirmed that these regulatory variants correlated with enhanced
      promoter activity and elevated expression of both mRNA and protein in solid
      cancer cells and tissues. We further demonstrated that heightened expression of
      MCL1 resulted in decreased proliferation ability of lung cancer cells. We found a
      reduced cancer risk (adjusted odds ratio [OR] = 0.47; 95% confidence interval
      [CI] = 0.25-0.88) associated with -190 insertional genotype. Stratification
      analysis further showed pronounced associations in nonsmokers (OR, 0.25; 95% CI,
      0.09-0.70), in females (OR, 0.22; 95% CI, 0.07-0.74), and in the histological
      type of adenocarcinoma (OR, 0.18; 95% CI, 0.05-0.62). Likewise, homologous
      diplotype of these polymorhpisms that positively affected gene expression was
      associated with reduced risk in nonsmokers (OR, 0.19; 95% CI, 0.06-0.58).
      CONCLUSION: The present study demonstrated that common variants in MCL1 promoter
      correlated with increased transactivation in solid cancer cells and were
      associated with reduced risk of lung cancer in nonsmokers, suggesting a dominant
      antiproliferative function of MCL1 against its antiapoptosis effect in
      development of solid cancer in nonsmokers.

PMID- 21887683
TI  - A meta-analysis evaluating stereotactic radiosurgery, whole-brain radiotherapy,
      or both for patients presenting with a limited number of brain metastases.
AB  - BACKGROUND: To perform a meta-analysis on newly diagnosed brain metastases
      patients treated with whole-brain radiotherapy (WBRT) and stereotactic
      radiosurgery (SRS) boost versus WBRT alone, or in patients treated with SRS alone
      versus WBRT and SRS boost. METHODS: The meta-analysis primary outcomes were
      overall survival (OS), local control (LC), and distant brain control (DBC).
      Secondary outcomes were neurocognition, quality of life (QOL), and toxicity.
      Using published Kaplan-Meier curves, results were pooled using hazard ratios
      (HR). RESULTS: Two RCTs reported on WBRT and SRS boost versus WBRT alone. For
      multiple brain metastases (2-4 tumors) we conclude no difference in OS, and LC
      significantly favored WBRT plus SRS boost. Three RCTs reported on SRS alone
      versus WBRT plus SRS boost (1-4 tumors). There was no difference in OS despite
      both LC and DBC significantly favoring WBRT plus SRS boost. Although secondary
      endpoints could not be pooled for meta-analysis, those RCTs evaluating SRS alone
      conclude better neurocognition using the validated Hopkins Verbal Learning Test,
      no adverse risk in deteriorating Mini-Mental Status Exam scores or in maintaining
      performance status, and fewer late toxicities. We conclude insufficient data for
      QOL outcomes. CONCLUSIONS: For selected patients, we conclude no OS benefit for
      WBRT plus SRS boost compared with SRS alone. Although additional WBRT improves
      DBC and LC, SRS alone should be considered a routine treatment option due to
      favorable neurocognitive outcomes, less risk of late side effects, and does not
      adversely affect the patients performance status.

PMID- 21887684
TI  - Occult tumor burden contributes to racial disparities in stage-specific
      colorectal cancer outcomes.
AB  - BACKGROUND: There are differences in outcomes in blacks compared with whites with
      lymph node-negative (pN0) colorectal cancer. Recurrence in pN0 patients suggests
      the presence of occult metastases undetected by conventional approaches. This
      study explores the association of racial differences in outcomes with occult
      tumor burden in regional lymph nodes. METHODS: Lymph nodes (range, 2-159) from
      282 prospectively enrolled pN0 colorectal cancer patients followed for a median
      of 24 months (range, 2-63 months) were subjected to molecular analysis. Occult
      tumor burden was estimated by quantifying the expression of GUCY2C, a biomarker
      for metastatic colorectal cancer cells. Risk categories defined using occult
      tumor burden was the primary outcome measure. Association of prognostic variables
      and risk were defined by multivariate polytomous logistic regression. RESULTS:
      Occult tumor burden stratified this cohort of 259 whites and 23 blacks into
      categories with low (60%; recurrence rate [RR] = 2.3%; 95% confidence interval
      [CI], 0.1%-4.5%), intermediate (31%; RR = 33.3%; 95% CI, 23.7%-44.1%), and high
      (9%; RR = 68.0%; 95% CI, 46.5%-85.1%; P < .001) risk. Blacks compared with whites
      exhibited 4-fold greater occult metastases in individual lymph nodes (P < .001).
      Multivariate analysis revealed that race (P = .02), T stage (P = .02), and number
      of lymph nodes collected (P = .003) were independent prognostic markers of risk
      category. Blacks compared with whites were more likely to harbor levels of occult
      tumor burden, associated with the highest recurrence risk (adjusted odds ratio =
      5.08; 95% CI, 1.69-21.39; P = .007). CONCLUSIONS: Racial disparities in stage
      specific outcomes in colorectal cancer are associated with differences in occult
      tumor burden in regional lymph nodes.

PMID- 21887685
TI  - A randomized phase 2 trial of a preparative regimen of bortezomib, high-dose
      melphalan, arsenic trioxide, and ascorbic acid.
AB  - BACKGROUND: Bortezomib is active for newly diagnosed and relapsed multiple
      myeloma, and it has synergistic activity with melphalan. The authors of this
      report conducted a randomized trial to determine the safety and efficacy of
      adding bortezomib to a preparative regimen of arsenic trioxide (ATO), ascorbic
      acid (AA), and melphalan. METHODS: Among 60 patients who enrolled between October
      2006 and September 2007, 58 patients underwent autologous transplantation with a
      preparative regimen of melphalan 200 mg/m(2) intravenously, AA 1000 mg daily
      intravenously for 7 days, and ATO 0.25 mg/kg intravenously for 7 days. Patients
      were randomized to receive no bortezomib (Group 1), bortezomib 1 mg/m(2) * 3
      doses (Group 2), and bortezomib 1.5 mg/m(2) * 3 doses (Group 3). Primary
      endpoints were complete response (CR), grade IV toxicity, and 90-day treatment
      related mortality (TRM). Secondary endpoints were progression-free survival (PFS)
      and overall survival (OS). RESULTS: The median follow-up of all surviving
      patients was 36 months (range, 20-43 months). The CR rates in Groups 1, 2, and 3
      were 20%, 10%, and 10%, respectively. Grade 3 and 4 nonhematologic toxicities and
      TRM were comparable. The median OS was not reached in the groups, whereas the
      median PFS in Groups 1, 2, and 3 was 17.8 months, 17.4 months, and 20.7 months,
      respectively. PFS and OS were significantly shorter in patients who had high-risk
      cytogenetics (P = .016 and P = .0001, respectively) and relapsed disease (P =
      .0001 and P = .0001, respectively) regardless of the treatment group.
      CONCLUSIONS: Adding bortezomib to a preparative regimen of ATO, AA, and high-dose
      melphalan was safe and well tolerated in patients with multiple myeloma. There
      was no significant improvement in the CR rate, PFS, or OS in the bortezomib
      groups.

PMID- 21887686
TI  - Molecular characterization of kidney cancer: association of hyaluronic acid
      family with histological subtypes and metastasis.
AB  - BACKGROUND: Molecular profiling of renal cell carcinomas (RCCs) may improve the
      distinction between oncocytoma and malignant RCC subtypes and aid in early
      detection of metastasis. The hyaluronic acid (HA) family includes HA synthases
      (HAS1, HAS2, HAS3), hyaluronidases (HYAL-1, HYAL-2, HYAL-3, HYAL-4, PH20, HYAL
      P1), and HA receptors (CD44s, CD44v, RHAMM). HA family members promote tumor
      growth and metastasis. The authors evaluated the expression of HA family members
      in kidney specimens. METHODS: By using quantitative polymerase chain reaction,
      mRNA levels of 12 HA family members were measured in tumor specimens obtained
      from 86 consecutive patients undergoing nephrectomy; 80 of them also provided
      normal specimens. Mean and median follow-up were 15.2 +/- 8.8 and 13.8 months.
      RCC specimens included clear cell RCC: 65; papillary: 10; chromophobe: 5;
      oncocytoma: 6; metastasis positive: 17. RESULTS: Median HAS1, CD44s, and RHAMM
      transcript levels were elevated 3- to 25-fold in clear cell RCC and papillary and
      chromophobe tumors when compared with normal tissues. HYAL-4, CD44s, and RHAMM
      levels were elevated 4- to 12-fold in clear cell RCC and papillary tumors when
      compared with oncocytomas; only HYAL-4 levels distinguished between chromophobe
      and oncocytoma (P = .009). CD44s and RHAMM levels were significantly higher in
      tumors <4 cm (510 +/- 611 and 19.6 +/- 20.8, respectively) when compared with
      oncocytoma (46.4 +/- 20 and 3.8 +/- 2.5; P <= .006). In univariate and
      multivariate analyses, CD44s (P < .0001), RHAMM (P < .0001), stage, tumor size,
      and/or renal vein involvement were significantly associated with metastasis. The
      combined CD44s + RHAMM marker had 82% sensitivity and 86% specificity to predict
      metastasis. CONCLUSIONS: CD44s and RHAMM levels distinguish between oncocytoma
      and RCC subtypes regardless of tumor size and are potential predictors of RCC
      metastasis.

PMID- 21887687
TI  - Left ventricular torsional mechanics in uncomplicated pregnancy.
AB  - BACKGROUND: Alterations in left ventricular (LV) twist (torsion) and untwist have
      been described for a variety of physiologic and pathologic conditions. Little
      information is available regarding changes in these parameters during normal
      pregnancy. HYPOTHESIS: Pregnancy is associated with significant changes in LV
      torsional mechanics. METHODS: Left ventricular twist and untwist was measured in
      32 pregnant females (mean gestation 199 +/- 48 d) and 23 nonpregnant controls
      using speckle-tracking echocardiography. RESULTS: Left ventricular ejection
      fraction (68 +/- 5% vs 66 +/- 5%) was similar between the groups (P not
      significant). There was a significant increase in peak LV twist from nonpregnant
      controls (9.4 +/- 3.7 degrees) to second-trimester (12.0 +/- 4.2 degrees) and
      third-trimester subjects (12.6 +/- 5.9 degrees, all P<0.05). Peak LV twist
      velocity was also increased in second- and third-trimester groups compared with
      controls (94 +/- 24 degrees/sec and 93 +/- 30 vs 64 +/- 21 degrees/sec,
      respectively, both P<0.05). Both peak untwist velocity and time to peak untwist
      velocity were not significantly different between groups (P not significant).
      Multiple regression analysis indicate that only systolic blood pressure (r =
      0.394, P = 0.005) was an independent predictor for increased LV torsion.
      CONCLUSIONS: There are significant changes in LV torsional indices during the
      course of pregnancy, whereas untwist parameters remain unchanged. Blood pressure
      is independently associated with increased torsion during pregnancy.

PMID- 21887688
TI  - HDL-C levels and revascularization procedures in coronary heart disease patients
      treated with statins to target LDL-C levels.
AB  - BACKGROUND: A low level of high-density lipoprotein cholesterol (HDL-C) is a
      strong predictor for cardiovascular disease morbidity and mortality at all low
      density lipoprotein cholesterol (LDL-C) concentrations. HYPOTHESIS: We evaluated
      this association in routine clinical practice among statin-treated coronary heart
      disease patients who achieved LDL-C target levels. This association also exists
      in routine clinical practice. METHODS: A retrospective dynamic cohort included
      all male coronary heart disease patients of the Sharon-Shomron district, Clalit
      Health Services, Israel, with LDL-C levels < 100 mg/dL and who were receiving
      statins (>= 6 purchases/y) from January 1998 to June 2008. Data were collected on
      demographic variables; coexistence of hypertension, diabetes mellitus, and
      peripheral vascular diseases; details of revascularization procedures; and lipid
      levels. The outcome variable was revascularization procedure, by either
      percutaneous intervention or coronary artery bypass graft. RESULTS: The study
      group of 909 male patients was stratified into quintiles, based on mean HDL-C
      levels: Q1 (n = 179): <= 26.4 mg/dL; Q2 (n = 190): 26.4-<= 30.0 mg/dL; Q3 (n =
      191): > 30.0-<= 34.0 mg/dL; Q4 (n = 186): > 34.0-<= 41.0 mg/dL; Q5 (n = 163): >
      41.0 mg/dL. During the study period, 307 (33.8%) of the cohort required >= 1
      revascularization procedure. Those in the highest quintile underwent
      significantly fewer procedures (40.8% for Q1 vs 16.6% for Q5, P<0.001). This
      significant effect of the highest HDL-C quintile was not influenced by any
      variable. CONCLUSIONS: The protective effect of high HDL-C levels, regardless of
      other risk factors, in preventing revascularization procedures was confirmed in
      the routine clinical practice among statin-treated CHD patients who reached LDL-C
      level < 100 mg/dL. Possible additional benefits of using agents to raise HDL-C
      levels should be investigated.

PMID- 21887689
TI  - Acquired long QT interval: a case series of multifactorial QT prolongation.
AB  - BACKGROUND: Acquired long QT (LQT) interval is thought to be a consequence of
      drug therapy and electrolyte disturbances. HYPOTHESIS: We characterize the
      potential effects of polypharmacy in a case series of acquired LQT and torsades
      de pointes (TdP) in order to determine whether multiple risk factors play a role
      in the development of LQT. METHODS: The case series consisted of 11 patients
      presenting to 4 tertiary care hospitals with LQT and >= 2 risk factors for
      developing LQT. Clinical characteristics, medications, electrolyte disturbances,
      and course in hospital were analyzed. RESULTS: Mean age was 49.1 +/- 5.8 years.
      Eight patients were female. Four had hypertension, 1 had a history of dilated
      cardiomyopathy, and 1 patient demonstrated complete atrioventricular block.
      Average QTc interval at presentation was 633.8 +/- 29.2 ms. Nine patients
      developed TdP. In 3, LQT was not initially detected and amiodarone was
      administered, followed by development of TdP. Patients were taking an average of
      2.8 +/- 0.3 QT-prolonging medications-an antidepressant in 6 cases and a diuretic
      in 8 cases. All patients had an electrolyte abnormality; 8 patients presented
      with severe hypokalemia (<3.0 mmol/L). Average serum potassium and magnesium were
      2.82 +/- 0.10 mmol/L and 0.75 +/- 0.03 mmol/L, respectively. There were no
      deaths. CONCLUSIONS: This case series highlights the risks of polypharmacy in the
      development of LQT and TdP. It illustrates the importance of early detection of
      LQT in patients with multiple risk factors in ensuring appropriate treatment.

PMID- 21887690
TI  - Comparison of ventricular tachyarrhythmia characteristics in patients with
      idiopathic dilated or ischemic cardiomyopathy and defibrillators implanted for
      primary prevention.
AB  - BACKGROUND: Implantable cardioverter-defibrillator (ICD) therapy for primary
      prevention is well established in ischemic cardiomyopathy (ICM). Data on the role
      of ICDs in patients with dilated cardiomyopathy (DCM) and no history of
      ventricular tachyarrhythmia (VT/VF) are more limited. HYPOTHESIS: DCM patients
      with an impaired left ventricular ejection fraction (LVEF) still represent a low
      arrhythmic risk subgroup in clinical practice. METHODS: ICD stored data of DCM
      patients with an LVEF <=35% was compared to data of ICM patients meeting
      Multicenter Automatic Defibrillator Implantation Trial (MADIT) eligibility
      criteria. VT/VF occurrences and electrical storm (ES) events were analyzed.
      RESULTS: There were 652 patients followed for 50.9 +/- 33.9 months. There were
      1978 VT and 241 VF episodes analyzed in 66 out of 203 patients (32.5%) with DCM
      and in 118 out of 449 patients (26.3%, P = 0.209) with ICM. Freedom of
      appropriate ICD treatment due to VT/VF or ES events did not differ in both
      patient populations (log-rank, P>0.05). In patients presenting with VT/VF
      episodes, mean event rates were comparable in both patient populations (3.2 +/-
      14.1 for DCM and VT vs 3 +/- 13.9 for ICM and VT [P = 0.855], 0.4 +/- 1.3 for DCM
      and VF vs 0.4 +/- 1.8 for ICM and VF [P = 0.763], and 0.2 +/- 0.7 for DCM and ES
      vs 0.2 +/- 1 for ICM and ES [P = 0.666]). CONCLUSIONS: DCM patients with
      prophylactic ICDs implanted due to heart failure and patients fulfilling MADIT
      criteria reveal comparable patterns of VT/VF/ES events during long-term follow
      up. Incidence, mean number of events, and time to first event did not differ
      significantly. Findings support the current guidelines for prophylactic ICD
      therapy in DCM patients with heart failure.

PMID- 21887691
TI  - Three-dimensional entertainment as a novel cause of takotsubo cardiomyopathy.
AB  - Takotsubo cardiomyopathy (TC) is an uncommon entity. It is known to occur in the
      setting of extreme catecholamine release and results in left ventricular
      dysfunction without evidence of angiographically definable coronary artery
      disease. There have been no published reports of TC occurring with visual
      stimuli, specifically 3-dimensional (3D) entertainment. We present a 55-year-old
      woman who presented to her primary care physician's office with extreme
      palpitations, nausea, vomiting, and malaise <48 hours after watching a 3D action
      movie at her local theater. Her electrocardiogram demonstrated ST elevations in
      aVL and V1, prolonged QTc interval, and T-wave inversions in leads I, II, aVL,
      and V2-V6. Coronary angiography revealed angiographically normal vessels,
      elevated left ventricular filling pressures, and decreased ejection fraction with
      a pattern of apical ballooning. The presumed final diagnosis was TC, likely due
      to visual-auditory-triggered catecholamine release causing impaired coronary
      microcirculation.

PMID- 21887692
TI  - Mildly decreased glomerular filtration rate is associated with poor coronary
      collateral circulation in patients with coronary artery disease.
AB  - BACKGROUND: The aim of this study was to evaluate the association between mildly
      decreased glomerular filtration rate (GFR) and coronary collateral circulation
      (CCC). HYPOTHESIS: There would be an association between mildly decreased GFR and
      CCC. METHODS: Patients who had an occlusion in at least 1 major coronary artery
      were included in this study. Patients with severely and moderately decreased GFR
      were excluded. Patient data were obtained from their files. To classify CCC, we
      used the Rentrop classification. Patients were classified as having poor CCC
      (Rentrop grades 0 to 1) or good CCC (Rentrop grades 2 to 3). We used the
      Modification of Diet in Renal Disease (MDRD) equation to calculate GFR. Mildly
      decreased GFR was defined as 60 mL/min per 1.73 m(2) >= eGFR <=89 mL/min per 1.73
      m(2) according to the MDRD definition. Multivariate logistic regression analysis
      was performed to determine independent variables. RESULTS: The study group
      consisted of 299 patients. Ninety-three patients had poor CCC and 206 patients
      had good CCC. The frequency of mildly decreased GFR was higher in the poor CCC
      group than in the good CCC group (P<0.001). Also, the frequency of diabetes and
      dyslipidemia, and the plasma high sensitive C-reactive protein levels, were
      higher in the poor CCC group (P = 0.003, P = 0.018, P<0.001, respectively).
      Logistic regression analysis revealed that eGFR is an independent predictor of
      CCC (B = 1.68; odds ratio = 5.4; P<0.001; 95% confidence interval, 3.1-9.4).
      CONCLUSIONS: We found that CCC was worse in patients with mildly decreased GFR
      compared to patients with normal GFR in patients with coronary artery disease.

PMID- 21887693
TI  - Effect of cardiac resynchronization therapy on thyroid function.
AB  - BACKGROUND: Heart failure patients frequently have thyroid function
      abnormalities. Cardiac resynchronization therapy (CRT) is a major treatment for
      patients with advanced chronic heart failure. We aimed to investigate the effects
      of CRT on thyroid functions. HYPOTHESIS: CRT improves thyroid functions. METHODS:
      Fifty-seven patients (42 male, 15 female; mean age 58 +/- 13 y) undergoing CRT
      were included in the study. Serum levels of thyroid hormones and
      echocardiographic parameters were measured before and 6 months after CRT. A
      response to CRT was defined as a reverse remodeling detected by a relative
      increase of >=15% in left ventricular ejection fraction. RESULTS: The clinical
      status and functional capacity of the patients in the remodeling group were
      improved significantly. The mean New York Heart Association class was reduced
      from 3.2 +/- 0.4 to 2.2 +/- 0.4 (P<0.001). The free triiodothyronine (fT3) level
      increased from 2.67 pg/mL to 2.97 pg/mL in the reverse remodeling group (P =
      0.005). The fT3/fT4 ratio increased from 1.81 to 2.34 (P = 0.006). CONCLUSIONS:
      CRT improves fT3 levels and fT3/fT4 ratio, which may play an important role in
      reverse remodeling.

PMID- 21887694
TI  - Antioxidant effect of red mould rice in hypercholesterolemic Wistar male rats.
AB  - The effect of Monascus purpureus red mould rice (RMR) on modulation of lipid
      metabolism and oxidative stress was studied in hypercholesterolemic rats.
      Cholesterol feeding for 14 weeks caused a significant increase in the lipid
      peroxides and total thiols and antioxidant enzymes, viz. glutathione peroxidase
      (GPx), glutathione reductase (GRd), superoxide dismutase (SOD) and catalase (CAT)
      in serum and liver in comparison to the control group. However, supplementation
      of RMR to hypercholesterolemic rats at 8, 12 and 16% significantly increased the
      GRd, GPx, SOD and CAT activities in serum and liver tissues. Furthermore, RMR
      feeding significantly decreased total thiols and lipid peroxides and also
      increased other antioxidant molecules such as glutathione and ascorbic acid in
      high-cholesterol fed rats. The efficiency of RMR (16%) in modulating the
      antioxidant molecules and antioxidant enzymes is comparable to standard drug
      lovastatin. Thus, this study suggests that the long-term administration of RMR
      may play an important role in suppressing oxidative stress and, thus, may be
      useful for the prevention and/or early treatment of hypercholesterolemia.

PMID- 21887695
TI  - Divergent cytokine response following maximum progressive swimming in hot water.
AB  - Exercise promotes transitory alterations in cytokine secretion, and these changes
      are affected by exercise duration and intensity. Considering that exercise
      responses also are affected by environmental factors, the goal of the present
      study was to investigate the effect of water temperature on the cytokine response
      to maximum swimming. Swiss mice performed a maximum progressive swimming exercise
      at 31 or 38 degrees C, and plasma cytokine levels were evaluated immediately or
      1, 6 or 24 h after exercise. The cytokine profile after swimming at 31 degrees C
      was characterized by increased interleukin (IL)-6 and monocyte chemotactic
      protein-1 (MCP-1) levels, which peaked 1 h after exercise, suggesting an adequate
      inflammatory milieu to induce muscle regeneration. Transitory reductions in IL-10
      and IL-12 levels also were observed after swimming at 31 degrees C. The cytokine
      response to swimming was modified when the water temperature was increased to 38
      degrees C. Although exercise at 38 degrees C also led to IL-6 secretion, the peak
      in IL-6 production occurred 6 h after exercise, and IL-6 levels were
      significantly lower than those observed after maximum swimming at 31 degrees C (p
      = 0.030). Furthermore, MCP-1 levels were lower and tumour necrosis factor-alpha
      levels were higher immediately after swimming at 38 degrees C, suggesting a
      dysregulated pro-inflammatory milieu. These alterations in the cytokine profile
      can be attributed in part to reduced exercise total work because exhaustion
      occurred sooner in mice swimming at 38 degrees C than in those swimming at 31
      degrees C.

PMID- 21887696
TI  - Induction of apoptotic death by curcumin in human tongue squamous cell carcinoma
      SCC-4 cells is mediated through endoplasmic reticulum stress and mitochondria
      dependent pathways.
AB  - Curcumin from the rhizome of the Curcuma longa plant has been noted for its chemo
      preventative and chemo-therapy activities, and it inhibits the growth of many
      types of human cancer cell lines. In this study, the mechanisms of cell death
      involved in curcumin-induced growth inhibition, including cell cycle arrest and
      induction of apoptosis in human tongue cancer SCC-4 cells, were investigated.
      Herein, we observed that curcumin inhibited cell growth of SCC-4 cells and
      induced cell death in a dose-dependent manner. Treatment of SCC-4 cells with
      curcumin caused a moderate and promoted the G(2) /M phase arrest, which was
      accompanied with decreases in cyclin B/CDK1 and CDC25C protein levels. Moreover,
      curcumin significantly induced apoptosis of SCC-4 cells with a decrease of the
      Bcl-2 level, reduction of mitochondrial membrane potential (DeltaPsi(m) ), and
      promoted the active forms of caspase-3. Curcumin also promoted the releases of
      AIF and Endo G from the mitochondria in SCC-4 cells by using confocal laser
      microscope. Therefore, we suggest that curcumin induced apoptosis through a
      mitochondria-dependent pathway in SCC-4 cells. In addition, we also found that
      curcumin-induced apoptosis of SCC-4 cells was partly through endoplasmic
      reticulum stress. In conclusion, curcumin increased G(2) /M phase arrest and
      induced apoptosis through ER stress and mitochondria-dependent pathways in SCC-4
      cells.

PMID- 21887697
TI  - Modulation of protein expression levels and DNA methylation status of breast
      cancer metastasis genes by anthracycline-based chemotherapy and the demethylating
      agent decitabine.
AB  - Epigenetic drugs are promising add-ons to cancer treatment; still, adverse
      effects concerning tumour promotion have been reported occasionally. In this in
      vitro study, we investigated the effect of combination treatment of decitabine
      with anthracycline-based chemotherapy [5-fluorouracil plus epirubicine plus
      cyclophosphamide (FEC)] on viability and metastatic activity of breast cancer
      cell lines, MDA-MB-231 (estrogen receptor-negative) and MCF-7 (estrogen receptor
      positive). The effect of decitabine and its combined treatment with FEC on
      viability of both cancer cell lines was assessed using the 3-(4,5-dimethylthiazol
      2-yl)-2,5-diphenyltetrazoliumbromide and adenosine triphosphate (ATP) cell
      survival assays. DNA methylation specific real-time polymerase chain reaction
      (PCR) (Methylight(r)) was employed to document the methylation status of the
      metastasis-relevant urokinase-type plasminogen activator (uPA) and plasminogen
      activator inhibitor-I (PAI-1) genes. Additionally, protein expression levels of
      uPA and PAI-1 were determined using enzyme-linked immunosorbent assays. Invasion
      capacity of cells was assayed using Matrigel(r) invasion assay. Decitabine
      lowered the viability of MCF-7 cells, although MDA-MB-231 cells were not
      affected. Decitabine did not augment FEC-mediated cytotoxicity in both cell
      lines. In MCF-7 cells, methylation of the uPA and PAI-1 gene promoter was
      significantly reduced by decitabine or decitabine plus FEC. Protein levels of uPA
      and PAI-1 were induced by all treatments. Decitabine significantly induced the
      invasion capacity of MCF-7 cells, whereas all of the drugs resulted in decreased
      invasion capacity of MDA-MB-231. Our results suggest differential effects of
      single-dose decitabine and its combination with FEC on the metastatic capacity
      and survival of breast cancer cell lines endowed with different metastatic
      behaviour.

PMID- 21887698
TI  - MicroRNA-194 is a target of transcription factor 1 (Tcf1, HNF1alpha) in adult
      liver and controls expression of frizzled-6.
AB  - Transcription factor 1 (Tcf1; hepatocyte nuclear factor 1alpha [HNF1alpha]) is
      critical for hepatocyte development and function. Whether Tcf1 also regulates
      hepatic microRNAs (miRNAs) has not been investigated yet. Here we analyzed Tcf1
      dependent miRNA expression in adult mice in which this transcription factor had
      been genetically deleted (Tcf1(-/-) ) using miRNA microarray analysis. The miR
      192/-194 cluster was markedly down-regulated in liver of Tcf1(-/-) mice. MiR-192/
      194 levels were also decreased in two other tissues that express Tcf1, kidney and
      small intestine, although to a lesser extent than in liver. In order to identify
      targets of miR-192/-194 in vivo we combined Affymetrix gene analysis of liver in
      which miR-192/-194 had been silenced or overexpressed, respectively, and tested
      regulated messenger RNAs (mRNAs) with multiple binding sites for these miRNAs.
      This approach revealed frizzled-6 (Fzd6) as a robust endogenous target of miR
      194. MiR-194 also targets human FZD6 and expression of miR-194 and Fzd6 are
      inversely correlated in a mouse model of hepatocellular carcinoma
      (Dgcr8(flox/flox) p53(flox/flox) * Alb-Cre). CONCLUSION: Our results support a
      role of miR-194 in liver tumorigenesis through its endogenous target Fzd6. These
      results may have important implications for Tcf1-mediated liver proliferation.

PMID- 21887700
TI  - Knee biomechanics early after knee replacement surgery predict abnormal gait
      patterns 12 months postoperatively.
AB  - An abnormal flexor moment pattern is often evident following total knee
      replacement (TKR) surgery. We investigated whether such a pattern at 12 months
      post-surgery could be predicted using biomechanical gait measures assessed before
      surgery and at 4 months post-surgery. Thirty two TKR patients were evaluated and
      classified as normal (biphasic pattern) or abnormal (flexor moment pattern) at
      each time point. Biomechanical parameters collected before surgery and at 4
      months post-surgery were then explored for their ability to predict gait patterns
      at 12 months post-surgery. The gait pattern at 4 months was significantly
      associated with the 12 month post-surgery gait pattern, with over half of those
      with a flexor moment pattern at 4 months retaining this pattern at 12 months.
      Discriminant function analysis indicated that peak knee flexion during early
      stance, peak knee extension, and peak knee extension moment at 4 months post
      surgery were independent predictors of the gait pattern at 12 months. Thus, an
      abnormal knee flexor moment pattern at 12 months post-surgery can be predicted by
      biomechanical analysis 4 months after surgery. Therefore, interventions aimed at
      improving active extension may need to be implemented early after surgery to
      restore a normal gait pattern.

PMID- 21887699
TI  - Proline substitutions and threonine pseudophosphorylation of the SH3 ligand of
      18.5-kDa myelin basic protein decrease its affinity for the Fyn-SH3 domain and
      alter process development and protein localization in oligodendrocytes.
AB  - The developmentally regulated myelin basic proteins (MBPs), which arise from the
      golli (gene of oligodendrocyte lineage) complex, are highly positively charged,
      intrinsically disordered, multifunctional proteins having several alternatively
      spliced isoforms and posttranslational modifications, and they play key roles in
      myelin compaction. The classic 18.5-kDa MBP isoform has a proline-rich region
      comprising amino acids 92-99 (murine sequence -T(92)PRTPPPS(99)-) that contains a
      minimal SH3 ligand domain. We have previously shown that 18.5-kDa MBP binds to
      several SH3 domains, including that of Fyn, a member of the Src family of
      tyrosine kinases involved in a number of signaling pathways during CNS
      development. To determine the physiological role of this binding as well as the
      role of phosphorylation of Thr92 and Thr95, in the current study we have produced
      several MBP variants specifically targeting phosphorylation sites and key
      structural regions of MBP's SH3 ligand domain. Using isothermal titration
      calorimetry, we have demonstrated that, compared with the wild-type protein,
      these variants have lower affinity for the SH3 domain of Fyn. Moreover,
      overexpression of N-terminal-tagged GFP versions in immortalized oligodendroglial
      N19 and N20.1 cell cultures results in aberrant elongation of membrane processes
      and increased branching complexity and inhibits the ability of MBP to decrease
      Ca(2+) influx. Phosphorylation of Thr92 can also cause MBP to traffic to the
      nucleus, where it may participate in additional protein-protein interactions.
      Coexpression of MBP with a constitutively active form of Fyn kinase resulted in
      membrane process elaboration, a phenomenon that was abolished by point amino acid
      substitutions in MBP's SH3 ligand domain. These results suggest that MBP's SH3
      ligand domain plays a key role in intracellular protein interactions in vivo and
      may be required for proper membrane elaboration of developing oligodendrocytes
      and, further, that phosphorylation of Thr92 and Thr95 can regulate this function.

PMID- 21887701
TI  - Bone microarchitecture assessed by TBS predicts osteoporotic fractures
      independent of bone density: the Manitoba study.
AB  - The measurement of BMD by dual-energy X-ray absorptiometry (DXA) is the "gold
      standard" for diagnosing osteoporosis but does not directly reflect deterioration
      in bone microarchitecture. The trabecular bone score (TBS), a novel gray-level
      texture measurement that can be extracted from DXA images, correlates with 3D
      parameters of bone microarchitecture. Our aim was to evaluate the ability of
      lumbar spine TBS to predict future clinical osteoporotic fractures. A total of
      29,407 women 50 years of age or older at the time of baseline hip and spine DXA
      were identified from a database containing all clinical results for the Province
      of Manitoba, Canada. Health service records were assessed for the incidence of
      nontraumatic osteoporotic fracture codes subsequent to BMD testing (mean follow
      up 4.7 years). Lumbar spine TBS was derived for each spine DXA examination
      blinded to clinical parameters and outcomes. Osteoporotic fractures were
      identified in 1668 (5.7%) women, including 439 (1.5%) spine and 293 (1.0%) hip
      fractures. Significantly lower spine TBS and BMD were identified in women with
      major osteoporotic, spine, and hip fractures (all p < 0.0001). Spine TBS and BMD
      predicted fractures equally well, and the combination was superior to either
      measurement alone (p < 0.001). Spine TBS predicts osteoporotic fractures and
      provides information that is independent of spine and hip BMD. Combining the TBS
      trabecular texture index with BMD incrementally improves fracture prediction in
      postmenopausal women.

PMID- 21887702
TI  - Gender-specific increase of bone mass by CART peptide treatment is ovary
      dependent.
AB  - Cocaine- and amphetamine-regulated transcript (CART) has emerged as a
      neurotransmitter and hormone that has been implicated in many processes including
      food intake, maintenance of body weight, and reward, but also in the regulation
      of bone mass. CART-deficient mice are characterized by an osteoporotic phenotype,
      whereas female transgenic mice overexpressing CART display an increase in bone
      mass. Here we describe experiments that show that peripheral subcutaneous
      sustained release of different CART peptide isoforms for a period up to 60 days
      increased bone mass by 80% in intact mice. CART peptides increased trabecular
      bone mass, but not cortical bone mass, and the increase was caused by reduced
      osteoclast activity in combination with normal osteoblast activity. The observed
      effect on bone was gender-specific, because male mice did not respond to
      treatment with CART peptides. In addition, male transgenic CART overexpressing
      mice did not display increased bone mass. Ovariectomy (OVX) completely abolished
      the increase of bone mass by CART peptides, both in CART peptide-treated wild
      type mice and in CART transgenic mice. The effect of CART peptide treatment on
      trabecular bone was not mediated by 17beta-estradiol (E(2)) because
      supplementation of OVX mice with E(2) could not rescue the effect of CART
      peptides on bone. Together, these results indicate that sustained release of CART
      peptides increases bone mass in a gender-specific way via a yet unknown mechanism
      that requires the presence of the ovary.

PMID- 21887703
TI  - Physiological function of the angiotensin AT1a receptor in bone remodeling.
AB  - In order to determine whether the renin-angiotensin system (RAS) has any
      physiologic function in bone metabolism, mice lacking the gene encoding the major
      angiotensin II receptor isoform, AT1a, were studied using micro CT scanning,
      histomorphometric, and biochemical techniques. Three-dimensional (3D) micro CT
      analysis of the tibial metaphysis revealed that both male and female AT1a
      knockout mice exhibited an increased trabecular bone volume along with increased
      trabecular number and connectivity. Histomorphometric analysis of the tibial
      metaphysis indicated that the parameters of bone formation as well as resorption
      were increased, which was also supported by elevated serum osteocalcin and
      carboxy-terminal collagen crosslink (CTX) concentrations in the AT1a-deficient
      mice. Osteoclastogenesis and osteoblastogenesis assays in ex vivo cultures,
      however, did not reveal any intrinsic alterations in the differentiation
      potential of AT1a-deficient cells. Quantitative RT-PCR using RNA isolated from
      the tibia and femur revealed that the receptor activator of NF-kappaB ligand
      (RANKL)/osteoprotegerin (OPG) ratio and the expression of stromal cell-derived
      factor (SDF)1alpha were increased, whereas that of SOST was decreased in AT1a
      deficient bone, which may account for the increased bone resorption and
      formation, respectively. AT1a-deficient mice also displayed a lean phenotype with
      reduced serum leptin levels. They maintained high bone mass with advancing age,
      and were protected from bone loss induced by ovariectomy. Collectively, the data
      suggest that RAS has a physiologic function in bone remodeling, and that
      signaling through AT1a negatively regulates bone turnover and bone mass.

PMID- 21887705
TI  - Predicting fractures in an international cohort using risk factor algorithms
      without BMD.
AB  - Clinical risk factors are associated with increased probability of fracture in
      postmenopausal women. We sought to compare prediction models using self-reported
      clinical risk factors, excluding BMD, to predict incident fracture among
      postmenopausal women. The GLOW study enrolled women aged 55 years or older from
      723 primary-care practices in 10 countries. The population comprised 19,586 women
      aged 60 years or older who were not receiving antiosteoporosis medication and
      were followed annually for 2 years. Self-administered questionnaires were used to
      collect data on characteristics, fracture risk factors, previous fractures, and
      health status. The main outcome measure compares the C index for models using the
      WHO Fracture Risk (FRAX), the Garvan Fracture Risk Calculator (FRC), and a simple
      model using age and prior fracture. Over 2 years, 880 women reported incident
      fractures including 69 hip fractures, 468 "major fractures" (as defined by FRAX),
      and 583 "osteoporotic fractures" (as defined by FRC). Using baseline clinical
      risk factors, both FRAX and FRC showed a moderate ability to correctly order hip
      fracture times (C index for hip fracture 0.78 and 0.76, respectively). C indices
      for "major" and "osteoporotic" fractures showed lower values, at 0.61 and 0.64.
      Neither algorithm was better than the model based on age + fracture history alone
      (C index for hip fracture 0.78). In conclusion, estimation of fracture risk in an
      international primary-care population of postmenopausal women can be made using
      clinical risk factors alone without BMD. However, more sophisticated models
      incorporating multiple clinical risk factors including falls were not superior to
      more parsimonious models in predicting future fracture in this population.

PMID- 21887704
TI  - The critical role of the epidermal growth factor receptor in endochondral
      ossification.
AB  - Loss of epidermal growth factor receptor (EGFR) activity in mice alters growth
      plate development, impairs endochondral ossification, and retards growth.
      However, the detailed mechanism by which EGFR regulates endochondral bone
      formation is unknown. Here, we show that administration of an EGFR-specific small
      molecule inhibitor, gefitinib, into 1-month-old rats for 7 days produced profound
      defects in long bone growth plate cartilage characterized by epiphyseal growth
      plate thickening and massive accumulation of hypertrophic chondrocytes.
      Immunostaining demonstrated that growth plate chondrocytes express EGFR, but
      endothelial cells and osteoclasts show little to no expression. Gefitinib did not
      alter chondrocyte proliferation or differentiation and vascular invasion into the
      hypertrophic cartilage. However, osteoclast recruitment and differentiation at
      the chondro-osseous junction were attenuated owing to decreased RANKL expression
      in the growth plate. Moreover, gefitinib treatment inhibited the expression of
      matrix metalloproteinases (MMP-9, -13, and -14), increased the amount of collagen
      fibrils, and decreased degraded extracellular matrix products in the growth
      plate. In vitro, the EGFR ligand transforming growth factor alpha (TGF-alpha)
      strongly stimulated RANKL and MMPs expression and suppressed osteoprotegerin
      (OPG) expression in primary chondrocytes. In addition, a mouse model of cartilage
      specific EGFR inactivation exhibited a similar phenotype of hypertrophic
      cartilage enlargement. Together our data demonstrate that EGFR signaling supports
      osteoclastogenesis at the chondro-osseous junction and promotes chondrogenic
      expression of MMPs in the growth plate. Therefore, we conclude that EGFR
      signaling plays an essential role in the remodeling of growth plate cartilage
      extracellular matrix into bone during endochondral ossification.

PMID- 21887706
TI  - Runx2 contributes to murine Col10a1 gene regulation through direct interaction
      with its cis-enhancer.
AB  - We have recently shown that a 150-bp Col10a1 distal promoter (-4296 to -4147 bp)
      is sufficient to direct hypertrophic chondrocyte-specific reporter (LacZ)
      expression in vivo. More recently, through detailed sequence analysis we
      identified two putative tandem-repeat Runx2 binding sites within the 3'-end of
      this 150-bp region (TGTGGG-TGTGGC, -4187 to -4176 bp). Candidate electrophoretic
      mobility shift assay (EMSA), chromatin immunoprecipitation, and transfection
      studies demonstrate that these putative Runx2 sites bind Runx2 and mediate
      upregulated Col10a1/reporter activity in vitro. Transgenic studies using the 5'
      sequence without Runx2 sites were not able to drive the cell-specific LacZ
      reporter activity, suggesting the in vivo requirement of the Runx2 sites located
      in the 3'-end in mediating Col10a1/reporter expression. Indeed, mutating the
      Runx2 sites in the context of the 150-bp promoter abolishes its capacity to drive
      hypertrophic chondrocyte-specific reporter expression in transgenic mice. We have
      also generated multiple transgenic mouse lines using only the 3'-sequence
      containing the Runx2 sites to drive the LacZ gene. Interestingly, no hypertrophic
      chondrocyte-specific blue staining was observed in these transgenic mice.
      Together, our data support that Runx2 directly interacts with murine Col10a1 cis
      enhancer. This interaction is required but not sufficient for cell-specific
      Col10a1 promoter activity in vivo. Additional cooperative/repressive elements
      within the 5'- or 3'-sequences of this 150-bp promoter are needed to work with
      Runx2 together to mediate cell-specific Col10a1 expression. Further delineation
      of these elements/factors has the potential to identify novel therapeutic targets
      for multiple skeletal disorders, including osteoarthritis, that show abnormal
      Col10a1 expression and altered chondrocyte maturation.

PMID- 21887708
TI  - Paroxysmal cervical myoclonus.

PMID- 21887707
TI  - Calcium intake and prostate cancer among African Americans: effect modification
      by vitamin D receptor calcium absorption genotype.
AB  - High dietary intake of calcium has been classified as a probable cause of
      prostate cancer, although the mechanism underlying the association between
      dietary calcium and prostate cancer risk is unclear. The vitamin D receptor (VDR)
      is a key regulator of calcium absorption. In the small intestine, VDR expression
      is regulated by the CDX-2 transcription factor, which binds a polymorphic site in
      the VDR gene promoter. We examined VDR Cdx2 genotype and calcium intake, assessed
      by a food frequency questionnaire, in 533 African-American prostate cancer cases
      (256 with advanced stage at diagnosis, 277 with localized stage) and 250 African
      American controls who participated in the California Collaborative Prostate
      Cancer Study. We examined the effects of genotype, calcium intake, and diet-gene
      interactions by conditional logistic regression. Compared with men in the lowest
      quartile of calcium intake, men in the highest quartile had an approximately
      twofold increased risk of localized and advanced prostate cancer (odds ratio [OR]
      = 2.20, 95% confidence interval [CI] = 1.40, 3.46), with a significant dose
      response. Poor absorbers of calcium (VDR Cdx2 GG genotype) had a significantly
      lower risk of advanced prostate cancer (OR = 0.41, 95% CI = 0.19, 0.90). The gene
      calcium interaction was statistically significant (p = 0.03). Among men with
      calcium intake below the median (680 mg/day), carriers of the G allele had an
      approximately 50% decreased risk compared with men with the AA genotype. These
      findings suggest a link between prostate cancer risk and high intestinal
      absorption of calcium.

PMID- 21887709
TI  - Paroxysmal craniocervical dyskinesia as manifestation of frontal lobe epilepsy.

PMID- 21887710
TI  - Safety and efficacy of botulinum toxin type B for treatment of sialorrhea in
      Parkinson's disease: a prospective double-blind trial.
AB  - Sialorrhea (drooling) is a common symptom of Parkinson's disease (PD) that can
      significantly impair a patient's health and quality of life. Fifty-four PD
      subjects with troublesome sialorrhea were enrolled using a multicenter,
      randomized, double-blind, sequential-dose escalation design in which subjects
      received a single intraglandular treatment with botulinum toxin type B (doses of
      1,500 Units [0.3 mL]; 2,500 Units [0.5 ml]; or 3,500 Units [0.7 ml]) or placebo.
      Postinjection, subjects were followed acutely for 4 weeks and long-term for up to
      20 weeks. Safety/tolerability, as assessed by adverse events, was the primary
      outcome measure. Efficacy, as assessed by the Drooling Frequency and Severity
      Scale and unstimulated salivary flow rate, was secondary. Gastrointestinal
      related adverse events occurred more frequently in the active groups versus
      placebo group (31% vs 7%), with dry mouth being most common (15%). There were no
      serious adverse events attributed to botulinum toxin type B or discontinuations
      due to adverse events from treatment. At 4 weeks postinjection, Drooling
      Frequency and Severity Scale scores significantly improved versus placebo (-1.3
      +/- 1.3) in a dose-related manner (-2.1 +/- 1.2, P = 0.0191; -3.3 +/- 1.4, P <
      0.0001; -3.5 +/- 1.1, P < 0.0001, respectively) and unstimulated salivary flow
      rates significantly decreased in all active groups versus placebo (P <= 0.0009).
      Furthermore, treated subjects appeared to have more sustained improvement in
      sialorrhea than placebo subjects. We conclude that intraglandular injection of
      botulinum toxin type B was safe, tolerable, and efficacious in treating
      sialorrhea in PD patients. Additional studies are warranted to further confirm
      the drug's robust efficacy, as well as evaluate its effect with repeated dosing.

PMID- 21887711
TI  - Parkinson's disease and alpha-synuclein expression.
AB  - Genetic studies of Parkinson's disease over the last decade or more have
      revolutionized our understanding of this condition. alpha-Synuclein was the first
      gene to be linked to Parkinson's disease, and is arguably the most important: the
      protein is the principal constituent of Lewy bodies, and variation at its locus
      is the major genetic risk factor for sporadic disease. Intriguingly, duplications
      and triplications of the locus, as well as point mutations, cause familial
      disease. Therefore, subtle alterations of alpha-synuclein expression can manifest
      with a dramatic phenotype. We outline the clinical impact of alpha-synuclein
      locus multiplications, and the implications that this has for Parkinson's disease
      pathogenesis. Finally, we discuss potential strategies for disease-modifying
      therapies for this currently incurable disorder.

PMID- 21887712
TI  - CNS live imaging reveals a new mechanism of myelination: the liquid croissant
      model.
AB  - The overall morphology and with it associated the formation of myelin is
      generally thought to be resolved. Based on electron microscopic findings more
      than half a century ago, the current model of myelination describes all myelin
      membranes to run in parallel with the longitudinal axis of the axon and to form a
      smooth surface, reminiscent of a rolled up carpet. However, different studies in
      the past demonstrated a distinct myelin morphology with an uneven myelin surface
      contour that challenges the established concept. Even though the current model of
      myelination has since been recognized as insufficient, CNS myelin formation has
      not yet been investigated in real-time with the requisite technique and
      resolution. We therefore traced myelin growth in murine organotypic cerebellar
      slice cultures using high-resolution confocal live imaging, light and electron
      microscopy and assessed myelin morphology in young and adult mice by confocal
      microscopy. Our data verify that the myelin surface is indeed not smooth but runs
      in a bidirectional, regularly spaced coil along the axon in both young and adult
      mice. Time-lapse imaging revealed that the growth of coiled myelin turns emerges
      during myelin formation. We therefore propose the "liquid croissant" model as a
      new concept of myelination that overcomes not only some of the incongruences of
      previous myelination theories, but potentially also explains the development of
      certain myelin pathologies observed in remyelination and axonopathies.

PMID- 21887713
TI  - A postdeployment expressive writing intervention for military couples: a
      randomized controlled trial.
AB  - The current study tested the effectiveness of a brief expressive writing
      intervention on the marital adjustment of 102 military couples recently reunited
      following a deployment to Iraq or Afghanistan. Active duty soldiers and their
      spouses were randomly assigned to write about either their relationship or a
      nonemotional topic on 3 occasions on a single day. The resulting design included
      4 couple-level writing topic conditions: soldier-expressive/spouse-expressive,
      soldier-expressive/spouse-control, soldier-control/spouse-expressive, and soldier
      control/spouse-control. Participants completed marital adjustment measures before
      writing, 1 month, and 6 months after writing. When soldiers, but not spouses, did
      expressive writing, couples increased in marital satisfaction over the next
      month, particularly if the soldier had had high combat exposure.

PMID- 21887714
TI  - Posttraumatic stress and related symptoms among neglected and physically and
      sexually maltreated adolescents.
AB  - Posttraumatic stress disorder (PTSD) is common among maltreated youth, but few
      investigations compare neglect with other maltreatment types. This study examined
      84 adolescents who experienced neglect only, physical and/or sexual maltreatment
      only, or neglect with physical and/or sexual maltreatment. Symptoms of PTSD,
      dissociation, and depression were measured. Adolescents who experienced physical
      and/or sexual maltreatment, whether neglected or not, reported significantly
      greater symptomatology than adolescents who experienced neglect only (eta2 =
      .094). This difference applied to PTSD symptoms, dissociative amnesia,
      depersonalization and derealization, negative mood, and anhedonia. Adolescents
      exposed to neglect only displayed substantial psychopathology but less than that
      of other groups. The findings may reflect emerging cascade models of the etiology
      of symptoms of PTSD following extensive maltreatment history.

PMID- 21887715
TI  - Negishi cross-coupling reactions catalyzed by an aminophosphine-based nickel
      system: a reliable and general applicable reaction protocol for the high-yielding
      synthesis of biaryls.
AB  - Treatment of NMP solutions of NiCl(2) with 1,1',1''-(phosphanetriyl)tripiperidine
      (~2.05 equiv), dissolved in THF, in air at 25  degrees C forms a highly active
      catalytic system for the cross-coupling of a large variety of electronically
      activated, non-activated, deactivated, and ortho-substituted, heterocyclic, and
      functionalized aryl bromides and aryl chlorides with diarylzinc reagents. Very
      high levels of conversion and yields were obtained within 2 h at 60  degrees C in
      the presence of only 0.1 mol% of catalyst (based on nickel) and thus at catalyst
      loadings far lower than typically reported for nickel-catalyzed versions of the
      Negishi reaction. Various aryl halides-which may contain trifluoromethyl groups,
      fluorides, or other functional groups such as acetals, ketones, ethers, esters,
      lactones, amides, imines, anilines, alkenes, pyridines, quinolines, and
      pyrimidines-were successfully converted into the corresponding biaryls.
      Electronic and steric variations are tolerated in both reaction partners.
      Experimental observations indicate that a molecular (Ni(I)/Ni(III)) mechanism is
      operative.

PMID- 21887716
TI  - Construction of hydrogen-bonded ternary organic crystals derived from L-tartaric
      acid and their application to enantioseparation of secondary alcohols.
AB  - Ternary organic crystals consisting of an L-tartaric acid-derived dicarboxylic
      acid, a commercially available achiral diamine, and a chiral secondary alcohol
      have been developed and characterized by X-ray crystallography. 1D, 2D, and 3D
      hydrogen-bonded supramolecular networks were constructed, depending on the
      structure of the diamine used. Benzylic and aliphatic secondary alcohols were
      enantioselectively incorporated into the crystal and were successfully
      enantioseparated with up to 86 and 79% enantiomeric excess (ee), respectively.
      Selective incorporation of one enantiomer of 2-butanol, which is a small chiral
      aliphatic alcohol, was achieved by the cooperative effects of hydrogen bonds,
      CH...pi interactions, and van der Waals interactions between the guest and host
      molecules, with the aid of two water molecules. The high host potential of the
      binary supramolecular system is mainly attributed to the skewed conformation of
      two rigid aromatic groups of tartaric acid derivatives, which prevents dense
      packing of the molecules and enhances the formation of multicomponent inclusion
      crystals.

PMID- 21887717
TI  - Presence of cleaved caspase 3 in swine embryos of different developmental
      capacities produced by parthenogenetic activation.
AB  - This study assessed the presence of cleaved caspase 3 (CC3) during the in vitro
      development of swine embryos produced by parthenogenetic activation (PA). Embryos
      with high and low capacity to develop into blastocysts and the exposure to a
      caspase inhibitor (z-DEVD-fmk) were used to investigate the effect of CC3 on
      embryo development. The blastocyst rate (64.3% vs. 16.4%) and the average number
      of nuclei per blastocyst (39.7 vs. 19.8) were significantly higher (P < 0.05) in
      early- (before 24 hr) compared to late- (between 24 and 48 hr) cleaving embryos
      after PA. CC3 was mainly detected in the cytoplasm of Day-2 and -4 embryos, but
      was primarily localized in the nucleus of Day-5 and -6 embryos. The fluorescence
      signal for CC3 relative to negative controls was significantly higher (P < 0.05)
      in early- (2.42-fold) compared to late-cleaving (1.39-fold) embryos at Day 2 of
      culture. Treatment with z-DEVD-fmk during the first 24 or 48 hr of the culture
      period resulted in more embryos developing into blastocysts compared to the
      control group (55.8% and 55.1% vs. 37%, respectively; P < 0.05). This study
      confirmed the presence of CC3 in PA embryos from the two-cell to the blastocyst
      stage, and revealed that CC3 cellular-localization changed during embryo
      development. CC3 was shown to be more abundant in early-cleaving and more
      developmentally competent embryos compared to late-cleaving and less
      developmentally competent embryos. The inhibition of caspase activity at the
      beginning, but not at the end, of the culture period affected development of PA
      embryos.

PMID- 21887718
TI  - 4E-BP1 degradation and eIF4E truncation occur spatially distinctly in the porcine
      uterine epithelia and are features of noninvasive implantation in the pig.
AB  - The implantation of the blastocyst into the endometrium is an indispensable
      premise for successful embryonic development. This process is regulated by
      maternal and embryonic signals that influence gene expression at the
      translational level, among other processes. Recently, we have shown that
      proteolytical cleavage of the prototypical 25-kDa, mRNA cap-binding protein eIF4E
      produces a stable variant with a molecular mass of approximately 23 kDa
      exclusively in the porcine endometrium during implantation. This is accompanied
      by dephosphorylation and reduction of the abundant repressor 4E-BP1. Here, we
      investigate the distribution of the truncated eIF4E and of 4E-BP1 in the porcine
      uterine tissue, their binding in native samples, and we analyzed eIF4E-, eIF4G-,
      and 4E-BP1-specific proteolytic activities. Our results show that in pigs, the
      truncated eIF4E is located in the endometrial luminal epithelium during
      implantation. Neither glandulary tissue nor stroma expressed any truncated eIF4E.
      The reduced abundance of 4E-BP1 during implantation is mainly the result of decay
      in the glandular epithelia. Moreover, steroid replacements, in vitro protease
      assays, and cell lysate fractionation showed that eIF4E cleavage and 4E-BP1 decay
      both depended on the ovarian steroid hormones estradiol and progestrone, but
      these effects are the result of different proteolytic activities. Although eIF4G
      cleavage also depends on calcium, stimulation by these steroids could not be
      established. We propose that the translation initiation process in the
      endometrium is differently regulated by the truncated eIF4E, utilizing different
      abundances of 4E-BP1 and binding dynamic of eIF4E/4E-BP1 in distinct forms of
      implantation.

PMID- 21887719
TI  - Evolution of the acquisition of fertilization competence and polyspermy blocks
      during meiotic maturation.
AB  - In many animals, fully grown oocytes are arrested at prophase of meiosis I.
      Before or after ovulation/spawning, a secondary arrest occurs at metaphase of
      meiosis I or II (MI or II, respectively). MI arrest in the ovary is released
      after spawning, and is followed by fertilization, whereas MI and MII arrest after
      ovulation are released by fertilization. Insemination of isolated oocytes from
      the ovaries at an inappropriate time increases the rate of polyspermy, indicating
      that ovaries provide the proper environment for acquisition of the polyspermy
      blocks and the development of competence to be fertilized normally. Due to MI
      arrest in the ovaries or MI/MII arrest after ovulation/spawning, the fertilizable
      period can be elongated. Thus, MI and MII arrest may play a role in maintaining
      the cell-cycle phases to enable normal fertilization. Here, the evolution of
      fertilization timing is discussed.

PMID- 21887721
TI  - Polymorphisms in the 5' regulatory region of the GPR54 gene and their association
      with sexual maturity in cattle.

PMID- 21887720
TI  - Centrosome dynamics during mammalian oocyte maturation with a focus on meiotic
      spindle formation.
AB  - Oocyte maturation is an important process required to achieve optimal oocyte
      quality, and later affects fertilization potential and subsequent embryo
      development. The maturation process includes synchronized nuclear and cytoplasmic
      remodeling, in which cytoskeletal and centrosome dynamics play an important role
      and significantly participate in cellular signaling. Centrosome remodeling within
      the maturing oocyte is essential for accurate meioisis I and II spindle
      formation, specifically to separate chromosomes accurately during the two
      successive, highly asymmetric meiotic cell divisions. Centrosomal abnormalities
      result in inaccurate microtubule organization and inaccurate chromosome
      alignment, with failures in chromosome segregation leading to aneuploidy and
      chromosomal abnormalities. The present review is focused on cytoskeletal and
      centrosome remodeling during oocyte maturation, with specific attention to gamma
      tubulin, pericentrin, the Nuclear Mitotic Apparatus (NuMA) protein, and
      microtubule organization. Species-specific differences will be discussed for
      rodent (mouse) and non-rodent (bovine, porcine) species, and for human oocytes.

PMID- 21887722
TI  - Lipid rafts function in Ca2+ signaling responsible for activation of sperm
      motility and chemotaxis in the ascidian Ciona intestinalis.
AB  - Lipid rafts are specialized membrane microdomains that function as signaling
      platforms across plasma membranes of many animal and plant cells. Although there
      are several studies implicating the role of lipid rafts in capacitation of
      mammalian sperm, the function of these structures in sperm motility activation
      and chemotaxis remains unknown. In the ascidian Ciona intestinalis, egg-derived
      sperm activating- and attracting-factor (SAAF) induces both activation of sperm
      motility and sperm chemotaxis to the egg. Here we found that a lipid raft
      disrupter, methyl-beta-cyclodextrin (MCD), inhibited both SAAF-induced sperm
      motility activation and chemotaxis. MCD inhibited both SAAF-promoted synthesis of
      intracellular cyclic AMP and sperm motility induced by ionophore-mediated Ca(2+)
      entry, but not that induced by valinomycin-mediated hyperpolarization. Ca(2+)
      imaging revealed that lipid raft disruption inhibited Ca(2+) influx upon
      activation of sperm motility. The Ca(2+)-activated adenylyl cyclase was clearly
      inhibited by MCD in isolated lipid rafts. The results suggest that sperm lipid
      rafts function in signaling upstream of cAMP synthesis, most likely in SAAF
      induced Ca(2+) influx, and are required for Ca(2+)-dependent pathways underlying
      activation and chemotaxis in Ciona sperm.

PMID- 21887723
TI  - Measuring the effect of policy interventions at the population level: some
      methodological concerns.
AB  - Health policy evaluations estimate the response of population aggregate outcomes
      to interventions. However, clarity on the form of the expected causal
      relationship, the parameter identification strategy, and the mode of hypothesis
      testing is required to overcome a number of conceptual and methodological
      problems. We use the New Jersey statewide smoking ban as an example. We examine
      statewide admission rates for acute myocardial infarctions, strokes and lower
      limb fractures, and emergency room encounter rates for asthma exacerbations
      before and after the smoking ban. We discuss the identification options and show
      the sensitivity of estimates of the response function to different specifications
      of the stochastic and intervention components and to different modes of
      inference. Model misspecification is demonstrated by rolling Chow tests for
      structural breaks in repeated observations.

PMID- 21887724
TI  - Hematopoietic prostaglandin D synthase (H-Pgds) is expressed in the early
      embryonic gonad and participates to the initial nuclear translocation of the SOX9
      protein.
AB  - In mammals, the Prostaglandin D(2) (PGD(2) ) signaling pathway is involved in
      male gonadal development, regulating Sox9 gene expression and SOX9 protein
      subcellular localization through lipocalin prostaglandin D synthase (L-Pgds)
      activity. Nevertheless, because L-Pgds is downstream of Sox9, its expression
      cannot explain the initial nuclear translocation of the SOX9 protein. Here, we
      show that another source of PGD(2) , hematopoietic-Pgds (H-Pgds) enzyme is
      expressed in somatic and germ cells of the embryonic gonad of both sexes, as
      early as embryonic day (E) 10.5, before the onset of L-Pgds expression.
      Inhibition of H-Pgds activity by the specific HQL-79 inhibitor leads to impaired
      nuclear translocation of SOX9 protein in E11.5 Sertoli cells. Furthermore,
      analysis of H-Pgds(-/-) male embryonic gonads confirms abnormal subcellular
      localization of SOX9 protein at the E11.5 early stage of mouse testicular
      differentiation suggesting a role for H-Pgds-produced PGD(2) in the initial
      nuclear translocation of SOX9.

PMID- 21887725
TI  - Mutational spectrum in the Ca(2+)--activated cation channel gene TRPM4 in
      patients with cardiac conductance disturbances.
AB  - Very recently, mutations in the TRPM4 gene have been identified in four pedigrees
      as the cause of an autosomal dominant form of cardiac conduction disease. To
      determine the role of TRPM4 gene variations, the relative frequency of TRPM4
      mutations and associated phenotypes was assessed in a cohort of 160 unrelated
      patients with various types of inherited cardiac arrhythmic syndromes. In eight
      probands with atrioventricular block or right bundle branch block--five familial
      cases and three sporadic cases--a total of six novel and two published TRPM4
      mutations were identified. In patients with sinus node dysfunction, Brugada
      syndrome, or long-QT syndrome, no mutations were found. The novel mutations
      include six amino acid substitutions and appeared randomly distributed through
      predicted TRPM4 protein. In addition, eight polymorphic sites including two in
      frame deletions were found. Mutations separated from polymorphisms by absence in
      control individuals and familial cosegregation in some families. In summary,
      TRPM4 gene mutations appear to play a major role in cardiac conduction disease
      but not for other related syndromes so far. The phenotypes are variable and
      clearly suggestive of additional factors modulating the disease phenotype in some
      patients.

PMID- 21887726
TI  - Is there evidence to claim or deny association between variants of the multidrug
      resistance gene (MDR1 or ABCB1) and inflammatory bowel disease?
AB  - BACKGROUND: Inflammatory bowel disease (IBD) is a complex disease with a genetic
      background. Crohn's disease (CD) and ulcerative colitis (UC) are the two main
      types of IBD. There is indication that variants in the MDR1 gene are associated
      with development of IBD. However, the 20 published genetic association studies
      (GAS) for the three most popular variants in the MDR1 gene (C3435T, G2677T/A, and
      C1236T) have produced inclusive results. METHODS: In order to decrease the
      uncertainty of pooled risk effects and to explore the trend and stability of the
      risk effects, a meticulous meta-analysis, including cumulative and recursive
      cumulative meta-analysis, of the GAS related to the MDR1 gene with susceptibility
      to IBD was conducted. The risk effects were estimated based on the odds ratio
      (OR) of the allele contrast and the generalized odds ratio (OR(G) ). RESULTS: The
      analysis showed marginal significant association for the C3435T variant in UC:
      the risk estimate for the allele contrast was OR = 1.11 (1.00-1.22) and OR(G) =
      1.12 (1.01-1.27), indicating that a subject with high mutational load has a 12%
      higher probability of being diseased. The respective cumulative meta-analysis
      indicated a downward trend of association, as evidence accumulates with the
      association being significant during the whole published period. The cumulative
      meta-analysis for the other variants showed lack of any trend of association.
      However, the recursive cumulative meta-analysis showed that there is no
      sufficient evidence for denying or claiming an association for all variants.
      CONCLUSIONS: More evidence is needed to draw safe conclusions regarding the
      association of MDR1 variants and development of IBD.

PMID- 21887727
TI  - Effect of adalimumab on clinical laboratory parameters in patients with Crohn's
      disease: results from the CHARM trial.
AB  - BACKGROUND: Nutritional deficiencies and anemia are common in Crohn's disease
      (CD). METHODS: We evaluated the effect of adalimumab on changes in laboratory
      values using data from CHARM, in which patients were randomized to adalimumab 40
      mg every other week (eow), adalimumab 40 mg weekly, or placebo for 56 weeks. Mean
      changes in laboratory values from baseline to Weeks 26 and 56 were compared
      between adalimumab and placebo using analysis of covariance models. Percentages
      of patients with suboptimal laboratory values at Weeks 26 and 56 were compared
      between treatment groups using Cochran-Mantel-Haenszel (CMH) tests. Pearson
      correlation coefficients for associations between changes in Crohn's Disease
      Activity Index (CDAI) score and changes in laboratory values were estimated at
      Weeks 4, 26, and 56. RESULTS: The intention-to-treat analysis included 778
      patients randomized to adalimumab eow (N = 260), adalimumab weekly (N = 257), or
      placebo (N = 261). Baseline abnormalities in laboratory values were common across
      treatment groups. CMH tests revealed significantly lesser rates of suboptimal
      laboratory values with adalimumab vs. placebo at Week 26, including
      hypoalbuminemia, calcium deficiency, low hemoglobin, low hematocrit, low red
      blood cell count, elevated platelet count, and elevated C-reactive protein
      concentration (all P < 0.05). These improvements persisted at Week 56.
      Improvements in CDAI from baseline to Weeks 4, 26, and 56 were significantly
      correlated with changes from baseline for albumin, hemoglobin, and C-reactive
      protein (all P < 0.001). CONCLUSIONS: Adalimumab therapy for moderately to
      severely active CD was associated with significant improvements in nutritional,
      hematologic, and inflammatory markers.

PMID- 21887728
TI  - Lymphoma risk in children and young adults with inflammatory bowel disease:
      analysis of a large single-center cohort.
AB  - BACKGROUND: Prior studies suggest an increased risk of lymphoma in adults with
      inflammatory bowel disease (IBD). Cases of lymphoma have also been reported in
      children with IBD. However, the precise risk of lymphoma in relation to drug
      exposure has not been ascertained in children. METHODS: We conducted a single
      center, retrospective study of 1560 children and young adults with IBD evaluated
      at Children's Hospital Boston between 1979 and 2008. Of this group, 186 patients
      were excluded due to incorrect diagnosis, one-time second-opinion visits, or
      missing hospital records. The remaining 1374 patients had charts reviewed to
      determine whether lymphoma developed while they were receiving their clinical
      care at our institution and the duration of exposure to various IBD medications.
      The rate of lymphoma was calculated in patient-years of exposure for each class
      of medications utilized in IBD. RESULTS: Of 1374 patients (741 male; age at
      diagnosis 12.1 +/- 4.0 years; 791 Crohn's disease [CD], 535 ulcerative colitis
      [UC], 48 IBD unclassified), we identified two patients who developed lymphoma
      (one Hodgkin, one anaplastic large cell), in 6624 patient-years of follow-up
      (mean duration follow-up 4.8 years per patient). Both patients were males (ages
      12 and 18 years at time of lymphoma onset) and were receiving thiopurines but had
      not yet received biologics at the time of their cancer diagnosis. They were both
      treated with chemotherapy and are alive without cancer 32+ and 76+ months since
      diagnosis. The absolute incidence rate of lymphoma for patients having received
      thiopurines was 4.5 per 10,000 patient-years compared to the expected rate of
      0.58 per 10,000 patient-years, with a standardized incidence ratio (SIR) of 7.51
      (95% confidence interval [CI] 0.74-41.98). CONCLUSIONS: The overall risk of
      lymphoma in children with IBD is low, with only two cases seen in our hospital
      over a 30-year period. The lymphoma risk (as estimated by SIR) in children
      receiving thiopurines is comparable to that reported in studies of adults. While
      there may be an increased risk of lymphoma in children treated with thiopurines,
      the risk did not reach statistical significance in this large cohort.

PMID- 21887729
TI  - Genetics of inflammatory bowel disease in Asia: systematic review and meta
      analysis.
AB  - BACKGROUND: Inflammatory bowel diseases (IBD) result from an interaction between
      genetic and environmental factors. Preliminary findings suggest that
      susceptibility genes differ between IBD patients in Asia and the West. We aimed
      to evaluate disease-predisposing genes in Asian IBD patients. METHODS: A
      systematic review and meta-analysis were performed of published studies from 1950
      to 2010 using keyword searches in MEDLINE, EMBASE, EBM Reviews, and BIOSIS
      Previews. RESULTS: In all, 477 abstracts were identified and data extracted from
      93 studies, comprising 17,976 IBD patients and 27,350 age- and sex-matched
      controls. Major nucleotide oligomerization domain (NOD)-2 variants in Western
      Crohn's disease (CD) patients were not associated with CD in Han Chinese,
      Japanese, South Korean, Indian, and Malaysian populations. New NOD2 mutations
      were, however, associated with CD in Malaysians (JW1), Han Chinese, and Indians
      (P268S). Autophagy-related protein 16-linked 1 (ATG16L1) was not associated with
      CD in East Asians (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.84-1.13).
      Interleukin (IL)-23R was associated with CD in South Koreans (OR 1.8; 95% CI 1.16
      2.82) and a single nucleotide polymorphism in IL-23R (Gly149Arg) was protective
      of CD in Han Chinese (OR 0.3; 95% CI 0.15-0.60). Tumor necrosis factor (TNF)
      superfamily gene-15 (SF15) polymorphisms were associated with CD (OR 2.68; 95% CI
      1.86-3.86), while TNF-308 polymorphisms (OR 1.82; 95% CI 1.15-2.9), cytotoxic T
      lymphocyte antigen (CTLA)-4 (OR 2.75; 95% CI 1.22-6.22) and MICA allele (OR 2.41;
      95% CI 1.89-3.07) were associated with ulcerative colitis in Asians. CONCLUSIONS:
      Genetic mutations of IBD in Asians differ from Caucasians. New mutations and
      susceptibility genes identified in Asian IBD patients provide an opportunity to
      explore new disease-associated mechanisms in this population of rising incidence.

PMID- 21887730
TI  - Control of NOD2 and Rip2-dependent innate immune activation by GEF-H1.
AB  - BACKGROUND: Genetic variants of nucleotide-binding oligomerization domain 2
      (NOD2) lead to aberrant microbial recognition and can cause chronic inflammatory
      diseases in patients with Crohn's disease (CD). METHODS: We utilized gene
      specific siRNA mediated knockdown and expression of guanine nucleotide exchange
      factor H1 (GEF-H1) in wildtype, Rip2-, and Nod2-deficient macrophages, HCT-116
      and HEK 293 cells to determine the role of GEF-H1 in NOD2 and Rip2-mediated NF
      kappaB-dependent induction of proinflammatory cytokine expression. Confocal
      microscopy was used to determine subcellular distribution of GEF-H1, Rip2, and
      NOD2. RESULTS: We identified GEF-H1 as an unexpected component of innate immune
      regulation during microbial pattern recognition by NOD2. Surprisingly, GEF-H1
      mediated the activation of Rip2 during signaling by NOD2, but not in the presence
      of the 3020 insC variant of NOD2 associated with CD. GEF-H1 functioned downstream
      of NOD2 as part of Rip2-containing signaling complexes and was responsible for
      phosphorylation of Rip2 by Src tyrosine kinase. Rip2 variants lacking the
      tyrosine target of GEF-H1-mediated phosphorylation were unable to mediate NF
      kappaB activation in Rip2-deficient macrophages and failed to transduce NOD2
      signaling. GEF-H1 is required downstream of NOD2 as part of Rip2-containing
      signaling complexes for the activation of innate immune responses. CONCLUSIONS:
      GEF-H1 connects tyrosine kinase function to NOD-like receptor signaling and is
      fundamental to the regulation of microbial recognition by ubiquitous innate
      immune mechanisms mediated by Rip2 kinase.

PMID- 21887731
TI  - Enterotoxin-producing staphylococci cause intestinal inflammation by a
      combination of direct epithelial cytopathy and superantigen-mediated T-cell
      activation.
AB  - BACKGROUND: Enterotoxin-producing Staphylococcus aureus may cause severe
      inflammatory intestinal disease, particularly in infants or immunodeficient or
      elderly patients. They are also recognized to be associated with sudden infant
      death syndrome. Little is known, however, about mucosal responses to
      staphylococci. METHODS: The mucosal lesion in three infants with staphylococcal
      enterocolitis was assessed by immunohistochemistry and electron microscopy. The
      organisms underwent extensive molecular analysis. Their toxins were assessed for
      capacity to induce T-cell activation and host mucosal responses examined by in
      vitro organ culture. Epithelial responses were studied by coculture with HEp-2
      and Caco-2 cells. RESULTS: Intestinal biopsies from the patients showed marked
      epithelial damage with mucosal inflammation. The three staphylococci,
      representing two distinct clones, were methicillin-sensitive, producing SEG/I
      enterotoxins and Rho-inactivating EDIN toxins. Their enterotoxins potently
      activated T cells, but only whole organisms could induce in vitro enteropathy,
      characterized by remarkable epithelial desquamation uninhibited by tacrolimus.
      EDIN-producing staphylococci, but not their supernatants, induced striking
      cytopathy in HEp-2 epithelial cells but not in Caco-2 cells. Although HEp-2 and
      Caco-2 cells produced similar IL-8, CCL20, and cathelicidin LL37 responses upon
      bacterial exposure, only Caco-2 cells expressed mRNA for the beta-defensins HBD2
      and HBD3, while HEp-2 cells were unable to do so. CONCLUSIONS: Staphylococci
      induce enterocolitis by a combination of direct enterocyte cytopathy mediated by
      EDIN toxins, disrupting the epithelial barrier, and enterotoxin superantigen
      induced mucosal T-cell activation. Gut epithelial production of beta-defensins
      may contribute to host defense against invasive staphylococcal disease.

PMID- 21887732
TI  - Double-blind, placebo-controlled trial of oral tacrolimus (FK506) in the
      management of hospitalized patients with steroid-refractory ulcerative colitis.
AB  - BACKGROUND: We report a multicenter study of oral tacrolimus (FK506) therapy in
      steroid-refractory ulcerative colitis (UC). METHODS: In a placebo-controlled,
      double-blind study, 62 patients with steroid-refractory, moderate-to-severe UC
      were randomized into either a tacrolimus group or a placebo for 2 weeks. Patients
      were evaluated using the Disease Activity Index (DAI). As an entry criterion,
      patients had to have a total DAI score of 6 or more as well as a mucosal
      appearance subscore of 2 or 3. Clinical response was defined as improvement in
      all DAI subscores. Mucosal healing was defined as mucosal appearance subscore of
      0 or 1. Clinical remission was defined as a total DAI score <= 2 with an
      individual subscore of 0 or 1. RESULTS: The mean total DAI score at study entry
      was 9.8 +/- 1.61 in the tacrolimus group and 9.1 +/- 1.05 in the placebo group.
      At week 2 the clinical response rate was 50.0% (16/32) in the tacrolimus group
      and 13.3% (4/30) in the placebo group (P = 0.003). The rate of mucosal healing
      observed was 43.8% (14/32) in the tacrolimus group and 13.3% (4/30) in the
      placebo group (P = 0.012) and the rate of clinical remission observed was 9.4%
      (3/32) in the tacrolimus group and 0.0% (0/30) in the placebo group (P = 0.238).
      The therapies in this study were well tolerated, with only minor side effects.
      CONCLUSIONS: Oral tacrolimus therapy in patients with steroid-refractory UC
      shortened the acute phase and induced rapid mucosal healing. These results
      suggest that tacrolimus therapy is useful as an alternative therapy for steroid
      refractory UC.

PMID- 21887733
TI  - Staudinger ligation as a method for bioconjugation.
AB  - In 1919 the German chemist Hermann Staudinger was the first to describe the
      reaction between an azide and a phosphine. It was not until recently, however,
      that Bertozzi and co-workers recognized the potential of this reaction as a
      method for bioconjugation and transformed it into the so-called Staudinger
      ligation. The bio-orthogonal character of both the azide and the phosphine
      functions has resulted in the Staudinger ligation finding numerous applications
      in various complex biological systems. For example, the Staudinger ligation has
      been utilized to label glycans, lipids, DNA, and proteins. Moreover, the
      Staudinger ligation has been used as a synthetic method to construct
      glycopeptides, microarrays, and functional biopolymers. In the emerging field of
      bio-orthogonal ligation strategies, the Staudinger ligation has set a high
      standard to which most of the new techniques are often compared. This Review
      summarizes recent developments and new applications of the Staudinger ligation.

PMID- 21887734
TI  - A combined far-infrared spectroscopic and electrochemical approach for the study
      of iron-sulfur proteins.
AB  - Herein, we present the development of a far-infrared spectroscopic approach for
      studying metalloenzyme active sites in a redox-dependent manner. An
      electrochemical cell with 5 mm path and based on silicon windows was found to be
      appropriate for the measurement of aqueous solutions down to 200 cm(-1) . The
      cell was probed with the infrared redox signature of the metal-ligand vibrations
      of different iron-sulfur proteins. Each Fe-S cluster type was found to show a
      specific spectral signature. As a common feature, a downshift of the frequency of
      the Fe-S vibrations was seen upon reduction, in line with the increase of the Fe
      S bond. This downshift was found to be fully reversible. Electrochemically
      induced FTIR difference spectroscopy in the far infrared is now possible, opening
      new perspectives on the understanding of metalloproteins in function of the redox
      state.

PMID- 21887736
TI  - Radio frequency glow discharge-induced acidification of fluoropolymers.
AB  - Fluoropolymer surfaces are unique in view of the fact that they are quite inert,
      have low surface energies, and possess high thermal stabilities. Attempts to
      modify fluoropolymer surfaces have met with difficulties in that it is difficult
      to control the modification to maintain bulk characteristics of the polymer. In a
      previously described method, the replacement of a small fraction of surface
      fluorine by acid groups through radio frequency glow discharge created a surface
      with unexpected reactivity allowing for attachment of proteins in their active
      states. The present study demonstrates that 1-ethyl-3-[3-dimethylaminopropyl]
      carbodiimide hydrochloride (EDC) reacts with the acid groups on fluoropolymer
      surfaces in a novel reaction not previously described. This reaction yields an
      excellent leaving group in which a primary amine on proteins can substitute to
      form a covalent bond between a protein and these surfaces. In an earlier study,
      we demonstrated that collagen IV could be deposited on a modified PTFE surface
      using EDC as a linker. Once collagen IV is attached to the surface, it assembles
      to form a functional stratum resembling collagen IV in native basement membrane.
      In this study, we show data suggesting that the fluorine to carbon ratio
      determines the acidity of the fluoropolymer surfaces and how well collagen IV
      attaches to and assembles on four different fluoropolymer surfaces.

PMID- 21887735
TI  - Gallic acid provokes DNA damage and suppresses DNA repair gene expression in
      human prostate cancer PC-3 cells.
AB  - Our earlier studies have demonstrated that gallic acid (GA) induced cytotoxic
      effects including induction of apoptosis and DNA damage and inhibited the cell
      migration and invasion in human cancer cells. However, GA-affected DNA damage and
      repair gene expressions in human prostate cancer cells are still unclear. In this
      study, we investigated whether or not GA induces DNA damage and inhibits DNA
      repair gene expression in a human prostate cancer cell line (PC-3). The results
      from flow cytometric assay indicated that GA decreased the percentage of viable
      PC-3 cells in a dose- and time-dependent manner. PC-3 cells after exposure to
      different doses (50, 100, and 200 MUM) of GA and various periods of time (12, 24,
      and 48 h) led to a longer DNA migration smear (comet tail) occurred based on the
      single cell gel electrophoresis (comet assay). These observations indicated that
      GA-induced DNA damage in PC-3 cells, which also confirmed by 4,6-diamidino-2
      phenylindole dihydrochloride staining and DNA agarose gel electrophoresis.
      Alternatively, results from real-time polymerase chain reaction assay also
      indicated that GA inhibited ataxia telangiectasia mutated, ataxia-telangiectasia
      and Rad3-related, O6-methylguanine-DNA methyltransferase, DNA-dependent
      serine/threonine protein kinase, and p53 mRNA expressions in PC-3 cells. Taken
      together, the present study showed that GA caused DNA damage and inhibited DNA
      repair genes as well as both effects may be the critical factors for GA-inhibited
      growth of PC-3 cells in vitro.

PMID- 21887737
TI  - Assessment of decellularized porcine diaphragm conjugated with gold nanomaterials
      as a tissue scaffold for wound healing.
AB  - One million Americans suffer from chronic wounds every year with diabetics and
      older populations representing the majority. Mechanisms that may be responsible
      for the reduced healing response in these patients include reduction in growth
      factors or vascularization and an increase in free radical levels. The focus of
      this study was to develop a biocompatible gold/porcine diaphragm scaffold capable
      of sustaining fibroblast attachment and proliferation which was measured using
      viability and dsDNA assays. The free radical scavenging properties, as measured
      by ROS assays, were also investigated as a mechanism for improving the wound
      environment. Results indicated 69-89% viability for gold nanoparticle (AuNP)
      scaffolds and 51-74% for gold nanorod (AuNR) scaffolds as compared to 100% for
      decellularized scaffolds and 77% for crosslinked scaffolds. All scaffolds
      exhibited good cell attachment while AuNP-1X scaffolds showed the greatest cell
      proliferation with a 74% increase in dsDNA content from Day 3 to 7. AuNP-2X and
      AuNP-4X scaffolds generated higher levels of free radicals with AuNP-4X
      generating over twice as much as decellularized scaffolds. This study suggests
      the capability for gold/porcine diaphragm scaffolds to enhance cell proliferation
      while the modification of free radical generation appears to be dependent on
      nanomaterial shape and concentration.

PMID- 21887738
TI  - In vitro evaluation of 45S5 Bioglass(r)-derived glass-ceramic scaffolds coated
      with carbon nanotubes.
AB  - Highly porous (> 90% porosity) 45S5 Bioglass(r)-derived glass-ceramic scaffolds
      were fabricated by foam replication method, and coated with carbon nanotubes
      (CNT) (coating thickness: 1 MUm) using electrophoretic deposition (EPD). In vitro
      cell culture using mesenchymal stem cells (MSCs) was carried out on both scaffold
      systems (with and without CNT coating) over a 4-week period. By using
      AlamarBlueTM, BSA and alkaline phosphatase assays; the cell viability and
      differentiation were measured quantitatively measured and compared between the
      two scaffold types. The results showed that both scaffold systems are
      biocompatible with MSCs and they can support the cellular activity. No cytotoxic
      effects of CNT were observed under the conditions of the present experiments.
      Although a lower initial cell viability on the CNT-coated scaffolds was observed,
      no significant differences were found after 4 weeks of culture compared with the
      uncoated scaffolds. This work therefore shows that there is in principle no
      significant improvement of cellular responses by creating a CNT-coating on this
      type of highly bioactive scaffolds. However, the electrical conductivity
      introduced by the coating might have the potential to increase cell viability and
      differentiation when cell culture is carried out under the effect of electrical
      stimulation.

PMID- 21887739
TI  - Hemocompatibility and biofunctionality of two poly(2-(dimethylamino)ethyl
      methacrylate-co-poly(ethyleneglycol) copolymers.
AB  - To mask the antigenic sites of cells for cell therapies, especially for blood
      transfusion, we investigated the hemocompatibility of two poly(2
      (dimethylamino)ethyl methacrylate-co-poly(ethyleneglycol) compared with that of
      the homopolymer without PEG. Our strategy relies on the potential ability of
      these copolymers to self-assemble at the erythrocyte surface. The cationic
      sequence of the copolymer should be able to interact with the glycocalyx by ionic
      interaction. The other sequence, based on a polyethyleneglycol moiety, should
      prevent both nonspecific interactions and specific recognition of the biological
      surface. The hemocompatibility of these copolymers was assessed by analyzing
      alterations in human erythrocyte membrane viscoelasticity, morphology,
      granularity, and aggregation. Their properties to mask ABO system and three
      erythrocyte glycophorin sites were investigated. No alterations in the
      erythrocyte morphology were observed by confocal microscopy. On the other hand, a
      partial masking of different specific glycophorin sites leads to future
      optimization of the macromolecular structures of these functionalized copolymers.

PMID- 21887740
TI  - Novel injectable biodegradable glycol chitosan-based hydrogels crosslinked by
      Michael-type addition reaction with oligo(acryloyl carbonate)-b-poly(ethylene
      glycol)-b-oligo(acryloyl carbonate) copolymers.
AB  - Novel injectable biodegradable glycol chitosan hydrogels were developed based on
      thiolated glycol chitosan (GC-SH) and water soluble oligo(acryloyl carbonate)-b
      poly(ethylene glycol)-b-oligo(acryloyl carbonate) (OAC-PEG-OAC) triblock
      copolymers via Michael-type addition reaction. The rheology measurements showed
      that robust hydrogels were formed rapidly upon mixing aqueous solutions of GC-SH
      and OAC-PEG-OAC at remarkably low total polymer concentrations of 1.5-4.5 wt %
      under physiological conditions. The gelation times (varying from 10 s to 17 min)
      and storage moduli (100 to 4300 Pa) of hydrogels could be controlled by degrees
      of substitution (DS) of GC-SH, solution pH, and polymer concentration. These
      glycol chitosan hydrogels had microporous structures, low swelling and slow
      hydrolytic degradation (stable for over 6 months) under physiological conditions.
      Notably, these hydrogels were prone to enzymatic degradation with lysozyme. The
      multiple acryloyl functional groups of OAC-PEG-OAC allowed facile conjugation
      with thiol-containing biomolecules prior to gelation endowing hydrogels with
      specific bioactivity. The preliminary cell culture studies revealed that these
      glycol chitosan hydrogels were cell non-adhesive while Gly-Arg-Gly-Asp-Cys
      (GRGDC) peptide modified hydrogels could well support adhesion and growth of both
      MG63 osteoblast and L929 fibroblast cells. These rapidly in situ forming
      enzymatically biodegradable hybrid hydrogels have great potentials in the
      development of injectable cell-specific bioactive extracellular matrices for
      tissue engineering.

PMID- 21887741
TI  - Dual-functional electrospun poly(2-hydroxyethyl methacrylate).
AB  - Poly(2-hydroxyethyl methacrylate) (pHEMA) has been widely used in many biomedical
      applications due to its well-known biocompatibility. For tissue engineering
      applications, porous scaffolds that mimic fibrous structures of natural
      extracellular matrix and possess high surface-area-to-volume ratios are highly
      desirable. So far, a systematic approach to control diameter and morphology of
      pHEMA fibers has not been reported and potential applications of pHEMA fibers
      have barely been explored. In this work, pHEMA was synthesized and processed into
      fibrous scaffolds using an electrospinning approach. Fiber diameters from 270 nm
      to 3.6 MUm were achieved by controlling polymer solution concentration and
      electrospinning flow rate. Post-electrospinning thermal treatment significantly
      improves integrity of the electrospun membranes in water. The pHEMA microfibrous
      membranes exhibited water absorption up to 280% (w/w), whereas the pHEMA hydrogel
      only absorbed 70% water. Fibrinogen adsorption experiments demonstrate that the
      electrospun pHEMA fibers highly resist nonspecific protein adsorption. Hydroxyl
      groups on electrospun pHEMA fibers were further activated for protein
      immobilization. A bovine serum albumin (BSA) binding capacity as high as 120 mg
      BSA/g membrane was realized at an intermediate fiber diameter. The pHEMA fibrous
      scaffolds functionalized with collagen I significantly promoted fibroblast
      adhesion, spreading, and proliferation. We conclude that the electrospun pHEMA
      fibers are dual functional, that is, they resist nonspecific protein adsorption
      meanwhile abundant hydroxyl groups on fibers allow effective conjugation of
      biomolecules in a nonfouling background. High water absorption and dual
      functionality of the electrospun pHEMA fibers may lead to a number of potential
      applications such as wound dressings, tissue scaffolds, and affinity membranes.

PMID- 21887742
TI  - Electrospun nanofiber-based regeneration of cartilage enhanced by mesenchymal
      stem cells.
AB  - Application of biomaterials in combination with stem cells is a novel tissue
      engineering approach to regenerate cartilage. The objective of this study was to
      investigate the potential of poly(vinyl alcohol)/polycaprolactone (PVA/PCL)
      nanofiber scaffolds seeded with rabbit bone marrow-mesenchymal stem cell (BM-MSC)
      for cartilage tissue engineering in vitro and in vivo. We tested the
      biocompatibility and mechanical properties of nanofibrous scaffolds using
      scanning electron microscope, MTT assay, and tensile measurements. The capacity
      of MSC for chondrogenic differentiation on scaffolds was examined using reverse
      transcription-polymer chain reaction and immunostaining. For in vivo assessments,
      PVA/PCL nanofiber scaffolds with or without MSC were implanted into rabbit full
      thickness cartilage defects. To evaluate cartilage regeneration, semi
      quantitative grading and histological analysis were performed. Our results showed
      that PVA/PCL scaffolds supported the proliferation and chondrogenic
      differentiation of MSC in vitro. Moreover, the animals treated with cell-seeded
      PVA/PCL scaffolds showed improved healing of defects compared with untreated
      control and those which received cell-free scaffolds. Our findings suggest that
      PVA/PCL scaffolds incorporated with MSC can serve as a suitable graft for
      articular cartilage reconstruction.

PMID- 21887743
TI  - A novel polymer gel for the delivery of local therapies to intracranial tumors:
      In vivo safety evaluation.
AB  - The treatment of intracranial malignancies is limited by the ability of
      systemically administered therapies to cross the blood-brain barrier. Royer
      resorbable matrix, or R-Gel, is a dextran polymer administered in liquid form via
      needle injection. Within minutes of preparation, the polymer forms a gel and
      subsequently solidifies, thereby conforming to the dimensions of the injection
      cavity. R-Gel can accommodate a wide variety of therapeutic agents that may
      provide new options for local treatment delivery. This preclinical study
      evaluates the neurotoxicity of R-Gel implanted in the rat brain. Fifteen rats
      underwent intracranial administration of R-Gel (N = 9) or saline (N = 6) were
      monitored for systemic and neurotoxicity, and sacrificed at pre-determined time
      points. Animals that received the R-Gel injection demonstrated no behavioral
      changes or weight loss. Histopathologic analysis revealed an inflammatory
      response in both groups on day 3 and day 7 after implantation, which resolved by
      day 42. These results suggest that intracranial R-Gel is well tolerated.
      Therapeutic studies of chemotherapy-complexed R-Gel are underway.

PMID- 21887745
TI  - Design, synthesis, and polymerase-catalyzed incorporation of click-modified
      boronic acid-TTP analogues.
AB  - DNA molecules are known to be important materials in sensing, aptamer selection,
      nanocomputing, and construction of unique architectures. The incorporation of
      modified nucleobases affords unique DNA properties for applications in areas that
      would otherwise be difficult or not possible. Earlier, we demonstrated that the
      boronic acid moiety can be introduced into DNA through polymerase-catalyzed
      reactions. In order to study whether such incorporation by polymerase is a
      general phenomenon, we designed and synthesized four boronic acid-modified
      thymidine triphosphate (TTP) analogues. The synthesis of certain analogues was
      through the use of a single dialkyne tether for both the Sonogashira coupling
      with thymidine and the later Cu-mediated [3+2] cycloaddition for linking the
      boronic acid moiety. This approach is much more efficient than the previously
      described method, and paves the way for the preparation of a large number of
      boronic acid-modified TTPs with a diverse set of structural features. All
      analogues showed very good stability under polymerase chain reaction (PCR)
      conditions and were recognized as a substrate by DNA polymerase, and thus
      incorporated into DNA.

PMID- 21887744
TI  - Effects of dialdehyde starch on calcification of collagen matrix.
AB  - Dialdehyde starch (DAS), a polymeric aldehyde derived from naturally occurring
      polysaccharide, was used as an additive to the collagen (COL) matrix in an effort
      to improve its physical and biological properties. The effects of DAS on the
      thermal stability of COL were characterized by differential scanning calorimetry.
      The conformational changes in COL were characterized by resistance to protease
      degradation assay, residual amine analysis, and Fourier-transform infrared
      spectroscopy. To assess biocompatibility enhancement, the calcium content in
      porcine aortic valve interstitial cells (PAVICs) on exposure to cardiovascular
      stents coated with DAS-stabilized COL was examined using atomic absorption
      spectroscopy. Thermal stability of DAS-stabilized COL was affected by DAS in a
      concentration dependent manner, reaching maximum at the saturation concentration
      (DAS:COL = 1:120) and decreasing the thermal stability at the concentrations
      above saturation. In the long-term exposure condition (21 days), stents coated
      with DAS at the lowest concentration significantly reduced the calcification rate
      of PAVIC, when compared with bare stent (p = 0.001). DAS appears to be an
      efficient additive to the COL matrix in improving its physical and biological
      properties. Further optimization process is needed for the suitable crosslinking
      conditions of DAS, which subsequently enhances thermal strength and
      anticalcification activities of COL matrix.

PMID- 21887746
TI  - Steroid/triterpenoid functional molecules based on "click chemistry".
AB  - This Focus Review highlights the design and synthesis of various functional
      molecules based on steroid/triterpenoid as building blocks through the copper
      catalyzed azide-alkyne cycloaddition (CuAAC) "click" reaction, as well as their
      applications in bioactivity, recognition, and assembly. This method shows great
      promise to allow us to develop novel molecules with characteristic functions
      using the CuAAC "click" reaction.

PMID- 21887747
TI  - Self-suspended polyaniline doped with a protonic acid containing a polyethylene
      glycol segment.

PMID- 21887748
TI  - Reactions under the click chemistry philosophy employed in supramolecular and
      mechanostereochemical systems.
AB  - Supramolecular chemistry and mechanostereochemistry have been major beneficiaries
      of the concepts and reactions pioneered under the "click chemistry" philosophy.
      The success of the copper(I) 1,3-dipolar cycloaddition between azides and
      alkynes, resulting in the triazole ring has inspired the application of other
      emerging click reactions, for example, Diels-Alder cycloadditions, thiol-ene/yne
      chemistry, and nitrile N-oxide cycloadditions, towards the creation of advanced
      functional supramolecular and mechanostereochemical systems. In this Focus
      Review, recent advances in the use of click chemistry in these fields are
      highlighted.

PMID- 21887749
TI  - Anodic formation of Ti-V binary oxide mesosponge layers for supercapacitor
      applications.

PMID- 21887750
TI  - Synthesis of a novel lithocene that has aromatic-like nature with nonaromatic
      rings.

PMID- 21887752
TI  - Neurourology and Urodynamics. Editorial.

PMID- 21887755
TI  - Educating chemists for the future.

PMID- 21887758
TI  - Transformation of carbon dioxide with homogeneous transition-metal catalysts: a
      molecular solution to a global challenge?
AB  - A plethora of methods have been developed over the years so that carbon dioxide
      can be used as a reactant in organic synthesis. Given the abundance of this
      compound, its utilization in synthetic chemistry, particularly on an industrial
      scale, is still at a rather low level. In the last 35 years, considerable
      research has been performed to find catalytic routes to transform CO(2) into
      carboxylic acids, esters, lactones, and polymers in an economic way. This Review
      presents an overview of the available homogeneous catalytic routes that use
      carbon dioxide as a C(1) carbon source for the synthesis of industrial products
      as well as fine chemicals.

PMID- 21887759
TI  - Stable hexacenes through nitrogen substitution.

PMID- 21887760
TI  - Genetic engineering of biomimetic nanocomposites: diblock proteins, graphene, and
      nanofibrillated cellulose.

PMID- 21887762
TI  - 43rd Congress of the International Society of Paediatric Oncology (SIOP) 2011,
      Auckland, New Zealand, 28th-30th October, 2011. SIOP Abstracts.

PMID- 21887764
TI  - The effect of calcium phosphate bone substitute on defect resolution around a
      rough-surfaced dental implants in dogs.
AB  - Gap defects often exist around dental implants due to morphological differences
      between the natural tooth extraction socket and the dental implant. Techniques
      that can resolve such gap defects include implant surface modification and
      filling of the defects with bone substitutes. Modified surfaces are generally
      more effective in this regard than smooth surfaces. Favorable results have also
      been reported using bone substitutes. This study evaluated the effectiveness of a
      calcium phosphate (CaP) bone substitute for resolving gap defects around implant
      surfaces that have been treated with grit blasting and thermal etching. Implants
      were placed in edentulous areas in four mongrel dogs. Gap defects with a diameter
      of 2 mm were prepared surgically around the dental implants. These defects were
      either filled with CaP bone substitute (experimental group) or left unfilled
      (control group). Defects were evaluated after 8 and 16 weeks of healing. Block
      specimens were fixed, sectioned, and stained with hematoxylin and eosin.
      Histometric measurements revealed that healing in gap defects that had been
      filled with CaP bone substitute proceeded until 16 weeks. Total CaP degradation
      seemed to occur at between 4 and 8 weeks of healing. In conclusion, a more
      complete defect resolution was observed in gap defects filled with CaP bone
      substitute after 16 weeks than after 8 weeks of healing. The beneficial effects
      of filling in 2-mm gap defects around implants were attributed to the use of CaP
      bone substitute.

PMID- 21887765
TI  - Microstructure and characteristics of the metal-ceramic composite (MgCa-HA/TCP)
      fabricated by liquid metal infiltration.
AB  - In this article, a novel MgCa alloy-hydroxyapatite-tricalcium phosphate (HA/TCP)
      composite was fabricated using the liquid alloy infiltration technique. The
      feasibility of the composite for biomedical applications was studied through
      mechanical testing, electrochemical testing, immersion testing, and cell culture
      evaluation. It was shown that the composite had a strength about 200-fold higher
      than that of the original porous HA/TCP scaffold but retained half of the
      strength of the bulk MgCa alloy. The corrosion test indicated that the resulting
      composite exhibited an average corrosion rate of 0.029 mL cm-2 h-1 in the Hank's
      solution at 37 degrees C, which was slower than that of the bulk MgCa alloy
      alone. The indirect cytotoxicity evaluation revealed that 100% concentrated
      (i.e., undiluted or as-collected) extract of the MgCa-HA/TCP composite showed
      significant toxicity to L-929 and MG63 cells (p < 0.05). In contrast, the diluted
      extracts with 50 and 10% concentrations of the MgCa-HA/TCP composite exhibited a
      similar degree of cell viability (p > 0.05), equivalent to the grade I
      cytotoxicity of the standard ISO 10993-5: 1999.

PMID- 21887769
TI  - Correlation mapping method for generating microcirculation morphology from
      optical coherence tomography (OCT) intensity images.
AB  - Standard optical coherence tomography (OCT) in combination with software tools
      can be harnessed to generate vascular maps in vivo. In this study we have
      successfully combined a software algorithm based on correlation statistic to
      reveal microcirculation morphology on OCT intensity images of a mouse brain in
      vivo captured trans-cranially and through a cranial window. We were able to
      estimate vessel geometry at bifurcation as well as along vessel segments down-to
      mean diameters of about 24 MUm. Our technique has potential applications in
      cardiovascular-related parameter measurements such as volumetric flow as well as
      in assessing vascular density of normal and diseased tissue.

PMID- 21887771
TI  - Renewable chemicals: dehydroxylation of glycerol and polyols.
AB  - The production of renewable chemicals is gaining attention over the past few
      years. The natural resources from which they can be derived in a sustainable way
      are most abundant in sugars, cellulose and hemicellulose. These highly
      functionalized molecules need to be de-functionalized in order to be feedstocks
      for the chemical industry. A fundamentally different approach to chemistry thus
      becomes necessary, since the traditionally employed oil-based chemicals normally
      lack functionality. This new chemical toolbox needs to be designed to guarantee
      the demands of future generations at a reasonable price. The surplus of
      functionality in sugars and glycerol consists of alcohol groups. To yield
      suitable renewable chemicals these natural products need to be defunctionalized
      by means of dehydroxylation. Here we review the possible approaches and evaluate
      them from a fundamental chemical aspect.

PMID- 21887772
TI  - A Li-liquid cathode battery based on a hybrid electrolyte.

PMID- 21887774
TI  - Improved enzyme production by bio-pellets of Aspergillus niger: targeted
      morphology engineering using titanate microparticles.
AB  - The present study describes the design of bio-pellet morphologies of the
      industrial working horse Aspergillus niger strains in submerged culture. The
      novel approach recruits the intended addition of titanate microparticles
      (TiSiO(4), 8 um) to the growth medium. As tested for two recombinant strains
      producing fructofuranosidase and glucoamylase, the enzyme titer by the titanate
      enhanced cultures in shake flasks was increased 3.7-fold to 150 U/mL (for
      fructofuranosidase) and 9.5-fold to 190 U/mL (for glucoamylase) as compared to
      the control. This could be successfully utilized for improved enzyme production
      in stirred tank reactors. Stimulated by the particles, the achieved final
      glucoamylase activity of 1,080 U/mL (fed-batch) and 320 U/mL (batch) was
      sevenfold higher as compared to the conventional processes. The major reason for
      the enhanced production was the close association between the titanate particles
      and the fungal cells. Already below 2.5 g/L the micromaterial was found inside
      the pellets, including single particles embedded as 50-150 um particle aggregates
      in the center resulting in core shell pellets. With increasing titanate levels
      the pellet size decreased from 1,700 um (control) to 300 um. Fluorescence based
      resolution of GFP expression revealed that the large pellets of the control were
      only active in a 200 um surface layer. This matches with the critical penetration
      depth for nutrients and oxygen typically observed for fungal pellets. The biomass
      within the titanate derived fungal pellets, however, was completely active. This
      was due a reduced thickness of the biomass layer via smaller pellets as well as
      the core shell structure. Moreover, also the created loose inner pellet structure
      enabled a higher mass transfer and penetration depths for up to 500 um. The
      creation of core-shell pellets has not been achieved previously by the addition
      of microparticles, for example, made of talc or alumina. Due to this, the present
      work opens further possibilities to use microparticles for tailor-made morphology
      design of filamentous fungi, especially for pellet based processes which have a
      long and strong industrial relevance for industrial production.

PMID- 21887775
TI  - Management of late postoperative complications of bariatric surgery.
AB  - BACKGROUND: The prevalence of obesity is increasing worldwide and the past decade
      has witnessed an exponential rise in the number of bariatric operations
      performed. As a consequence, an increasing number of patients are presenting to
      non-specialist units with complications following bariatric procedures. This
      article outlines the management of the most common late postoperative
      complications that are likely to present to the general surgeon. METHODS: A
      search was conducted for late postoperative complications after bariatric surgery
      using PubMed, Embase, OVID and Google search engines, and combinations of the
      terms bariatric surgery, gastric bypass, gastric banding or sleeve gastrectomy,
      and late or delayed complications. Only studies with follow-up longer than 6
      months were included. RESULTS: The most common long-term complications after
      gastric banding include band slippage and erosion. Deflation or removal of the
      band is often required. Internal hernia, adhesions and anastomotic stenosis are
      common causes of intestinal obstruction after gastric bypass surgery.
      Hepatobiliary complications pose a particular challenge because of the altered
      anatomy. Functional disorders such as reflux and dumping, and nutritional
      deficiencies are common and should be differentiated from conditions that require
      urgent investigations and timely surgical intervention. CONCLUSION: The immediate
      management of bariatric patients presenting with complications outside the
      immediate postoperative period requires adherence to basic surgical principles.
      Accurate diagnosis often relies on high-quality contrast and cross-sectional
      imaging, and effective surgical intervention necessitates a broad understanding
      of the altered anatomy, advanced surgical skills and liaison with specialists in
      the field when necessary.

PMID- 21887776
TI  - Sentinel lymph node biopsy and survival in elderly patients with cutaneous
      melanoma (Br J Surg 2011; 98: 1400-1407).

PMID- 21887777
TI  - Cost-utility of bariatric surgery for morbid obesity in Finland.
AB  - BACKGROUND: The aim of this study was to evaluate the cost-utility of bariatric
      surgery (gastric bypass, sleeve gastrectomy and gastric banding) compared with
      ordinary treatment in the Finnish healthcare system. METHODS: Analysis was done
      from a healthcare provider's perspective using a combination of a decision tree
      and a Markov model, with a time horizon of 10 years. Health-related quality of
      life was estimated from a representative population survey, and other parameter
      values were based on registers, systematic reviews, controlled studies and expert
      opinion. RESULTS: In the base-case analysis, bariatric surgery was both more
      effective and less costly than the ordinary treatment. The mean costs were
      ?33,870 and ?50,495, and the mean number of quality-adjusted life-years 7.63 and
      7.05, for bariatric surgery and ordinary treatment respectively. Uncertainty
      around the parameter values was tested comprehensively in sensitivity analyses,
      and the results were robust. CONCLUSION: Surgery for morbid obesity increases
      health-related quality of life, and reduces the need for further treatments and
      total healthcare costs. According to this analysis, non-operative care would be
      more costly for the Finnish healthcare system on average after 5 years following
      surgery.

PMID- 21887778
TI  - Cost-utility of bariatric surgery for morbid obesity in Finland (Br J Surg 2011;
      98: 1422-1429) [corrected].

PMID- 21887779
TI  - Operative notes do not reflect reality in laparoscopic cholecystectomy (Br J Surg
      2011; 98: 1431-1436).

PMID- 21887781
TI  - The significant rectal neoplasm and mucosectomy by transanal endoscopic
      microsurgery (Br J Surg 2011; 98: 1342-1344).

PMID- 21887782
TI  - Surgeon volumes in oesophagogastric and hepatopancreatobiliary resectional
      surgery (Br J Surg 2011; 98: 891-893).

PMID- 21887786
TI  - M cells expressing the complement C5a receptor are efficient targets for mucosal
      vaccine delivery.
AB  - In the mucosal immune system, M cells are known as specialized epithelial cells
      that take up luminal antigens, although the receptors on M cells and the
      mechanism of antigen uptake into M cells are not well-understood. Here, we report
      the expression of the complement C5a receptor (C5aR) on the apical surface of M
      cells. C5ar mRNA expression in co-cultured Caco-2 human M-like cells was six-fold
      higher than in mono-cultured cells. C5aR expression was detected together with
      glycoprotein 2, an M-cell-specific protein, on the apical surface of M-like cells
      and mouse Peyer's patch M cells. Interestingly, after oral administration of
      Yersinia enterocolitica which expresses outer membrane protein H (OmpH) that is
      homologous to the Skp alpha1 domain of Escherichia coli, a ligand of C5aR, dense
      clustering and phosphorylation of C5aR were detected in M cells. Finally,
      targeted antigen delivery to M cells using C5aR as a receptor was achieved using
      the OmpH alpha1 of Y. enterocolitica such that the induction of ligand-conjugated
      antigen-specific immune responses was confirmed in mice after oral immunization
      of the OmpH beta1alpha1-conjugated antigen. Collectively, we identified C5aR
      expression on M cells and suggest that C5aR could be used as a target receptor
      for mucosal antigen delivery.

PMID- 21887787
TI  - Chemical reactivity of ethyl (6R)-6-[N-(2-chloro-4
      fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate (TAK-242) in vitro.
AB  - Ethyl (6R)-6-[N-(2-chloro-4-fluorophenyl)sulfamoyl]cyclohex-1-ene-1-carboxylate
      (TAK-242) was metabolized to cyclohexene and phenyl ring moieties in non-clinical
      pharmacokinetic studies and it was suggested that the cyclohexene ring moiety of
      TAK-242 is tightly bound to endogenous macromolecules. After incubation of TAK
      242 and glutathione (GSH) in phosphate buffer (pH 7.4) at 37  degrees C, TAK-242
      reacted with GSH to produce a glutathione conjugate of the cyclohexene ring
      moiety of TAK-242, which had been observed as a metabolite (M-SG) in non-clinical
      pharmacokinetic studies. Formation of M-SG was time dependent with a first order
      reaction and M-I, a metabolite from the phenyl ring moiety of TAK-242, was also
      produced in parallel. The formation of M-SG was accelerated with increasing pH,
      therefore it was indicated that TAK-242 reacted with GSH by a nucleophilic
      substitution reaction. Because glutathione transferase (GST) enhanced M-SG
      formation in vitro, it is expected that the conjugation of TAK-242 with GSH is
      also facilitated by GST in vivo in addition to a spontaneous chemical reaction.
      When radio-labeled TAK-242 ([cyclohexene ring-U-14C]TAK-242) was incubated with
      rat serum albumin (RSA) or human serum albumin (HSA) in vitro, the radioactive
      material was covalently bound to RSA and HSA, and M-I was generated
      simultaneously in the reaction mixture. The chemical structure of the TAK-242
      adduct covalently bound to HSA was characterized by the accurate mass spectra
      that cyclohexene ring moiety of TAK-242 was covalently bound to the lysine
      residue in HSA. The adduct was also detected in the plasma of rats and humans
      after single i.v. dosing of TAK-242 (in vivo).

PMID- 21887789
TI  - Preclinical risk assessment of drug-induced hypo- and hyperprolactinemia.
AB  - Drug-induced changes in prolactin signaling may obscure interpretation of
      preclinical toxicological endpoints. However, with informed consideration,
      classic hallmarks of hypo-/hyperprolactinemia can be recognized in short- and
      long-term rodent bioassays. Findings can be supported and expanded with
      additional in vivo and in vitro datasets. When taken together with human
      epidemiological evidence pertaining to the consequences of drug-induced hypo
      /hyperprolactinemia, such findings permit both an analysis of human relevance and
      an assessment of human risk.

PMID- 21887788
TI  - IL-33 synergizes with TCR and IL-12 signaling to promote the effector function of
      CD8+ T cells.
AB  - The effector functions of CD8(+)  T cells are influenced by tissue inflammatory
      microenvironments. IL-33, a member of the IL-1 family, acts as a danger signal
      after its release during cell necrosis. The IL-33/ST2 axis has been implicated in
      various Th2 responses. Its role in CD8(+)  T-cell-mediated immune response is,
      however, not known. Here we find that type 1 cytotoxic T (Tc1) cells cultured in
      vitro unexpectedly express high levels of the IL-33 receptor ST2. Interestingly,
      the expression of ST2 in Tc1 cells is dependent on T-bet, a master Th1/Tc1
      transcription factor. In addition, IL-33 enhances TCR-triggered IFN-gamma
      production. IL-33 together with IL-12 can stimulate IFN-gamma production in Tc1
      cells. Moreover, IL-33 synergizes with IL-12 to promote CD8(+)  T-cell effector
      function. The synergistic effect of IL-33 and IL-12 is partly mediated by
      Gadd45b. Together, these in vitro data establish a novel role of IL-33 in
      promoting effector type 1 adaptive immune responses.

PMID- 21887792
TI  - A two-part mixed-effects pattern-mixture model to handle zero-inflation and
      incompleteness in a longitudinal setting.
AB  - Two-part regression models are frequently used to analyze longitudinal count data
      with excess zeros, where the same set of subjects is repeatedly observed over
      time. In this context, several sources of heterogeneity may arise at individual
      level that affect the observed process. Further, longitudinal studies often
      suffer from missing values: individuals dropout of the study before its
      completion, and thus present incomplete data records. In this paper, we propose a
      finite mixture of hurdle models to face the heterogeneity problem, which is
      handled by introducing random effects with a discrete distribution; a pattern
      mixture approach is specified to deal with non-ignorable missing values. This
      approach helps us to consider overdispersed counts, while allowing for
      association between the two parts of the model, and for non-ignorable dropouts.
      The effectiveness of the proposal is tested through a simulation study. Finally,
      an application to real data on skin cancer is provided.

PMID- 21887793
TI  - Semiparametric estimation in copula models for bivariate sequential survival
      times.
AB  - Sequentially observed survival times are of interest in many studies but there
      are difficulties in analyzing such data using nonparametric or semiparametric
      methods. First, when the duration of followup is limited and the times for a
      given individual are not independent, induced dependent censoring arises for the
      second and subsequent survival times. Non-identifiability of the marginal
      survival distributions for second and later times is another issue, since they
      are observable only if preceding survival times for an individual are uncensored.
      In addition, in some studies a significant proportion of individuals may never
      have the first event. Fully parametric models can deal with these features, but
      robustness is a concern. We introduce a new approach to address these issues. We
      model the joint distribution of the successive survival times by using copula
      functions, and provide semiparametric estimation procedures in which copula
      parameters are estimated without parametric assumptions on the marginal
      distributions. This provides more robust estimates and checks on the fit of
      parametric models. The methodology is applied to a motivating example involving
      relapse and survival following colon cancer treatment.

PMID- 21887794
TI  - A simple and flexible Holm gatekeeping procedure.
AB  - Major objectives of a clinical trial are commonly stated in a hierarchical order
      as primary and secondary. The parallel gatekeeping testing strategy provides an
      opportunity to assess secondary objectives when all or partial primary objectives
      are achieved. The current available gatekeeping procedures have different pros
      and cons so users either need to justify the assumption associated with some
      procedures or tolerate suboptimal power performance of other procedures. By
      applying the Holm test with a flexible alpha splitting technique, we propose a
      procedure which (1) is powerful for assessing the primary objectives, (2) can be
      used when no assumption can be made on the dependency structure of test
      statistics, and (3) has the full flexibility to allocate user-preferred alpha to
      assess the secondary objectives based on the number of primary objectives
      achieved. A real clinical trial example is used for illustration of the proposed
      procedure.

PMID- 21887795
TI  - Analysis of covariance with pre-treatment measurements in randomized trials:
      comparison of equal and unequal slopes.
AB  - In randomized trials, an analysis of covariance (ANCOVA) is often used to analyze
      post-treatment measurements with pre-treatment measurements as a covariate to
      compare two treatment groups. Random allocation guarantees only equal variances
      of pre-treatment measurements. We hence consider data with unequal covariances
      and variances of post-treatment measurements without assuming normality.
      Recently, we showed that the actual type I error rate of the usual ANCOVA
      assuming equal slopes and equal residual variances is asymptotically at a nominal
      level under equal sample sizes, and that of the ANCOVA with unequal variances is
      asymptotically at a nominal level, even under unequal sample sizes. In this
      paper, we investigated the asymptotic properties of the ANCOVA with unequal
      slopes for such data. The estimators of the treatment effect at the observed mean
      are identical between equal and unequal variance assumptions, and these are
      asymptotically normal estimators for the treatment effect at the true mean.
      However, the variances of these estimators based on standard formulas are biased,
      and the actual type I error rates are not at a nominal level, irrespective of
      variance assumptions. In equal sample sizes, the efficiency of the usual ANCOVA
      assuming equal slopes and equal variances is asymptotically the same as those of
      the ANCOVA with unequal slopes and higher than that of the ANCOVA with equal
      slopes and unequal variances. Therefore, the use of the usual ANCOVA is
      appropriate in equal sample sizes.

PMID- 21887796
TI  - Latent variable modeling paradigms for genotype-trait association studies.
AB  - Characterizing associations among multiple single-nucleotide polymorphisms (SNPs)
      within and across genes, and measures of disease progression or disease status
      will potentially offer new insight into disease etiology and disease progression.
      However, this presents a significant analytic challenge due to the existence of
      multiple potentially informative genetic loci, as well as environmental and
      demographic factors, and the generally uncharacterized and complex relationships
      among them. Latent variable modeling approaches offer a natural framework for
      analysis of data arising from these population-based genetic association
      investigations of complex diseases as they are well-suited to uncover
      simultaneous effects of multiple markers. In this manuscript we describe
      application and performance of two such latent variable methods, namely
      structural equation models (SEMs) and mixed effects models (MEMs), and highlight
      their theoretical overlap. The relative advantages of each paradigm are
      investigated through simulation studies and, finally, an application to data
      arising from a study of anti-retroviral-associated dyslipidemia in HIV-infected
      individuals is provided for illustration.

PMID- 21887797
TI  - Synthesis and anticancer activity of 13-membered cyclic enediynes.
AB  - We herein describe the synthesis of 15 novel 13-membered cyclic enediyne
      derivatives using simple and straightforward approach. Representative examples
      were screened for their anticancer activities on 60 different human tumor cell
      lines representing various histologies viz. leukemia, melanoma, and cancers of
      lung, colon, kidney, ovary, breast, prostate, and central nervous system. The
      enediyne derivatives with halogen substitutions, especially fluorides were found
      to be active against most of the cell lines. The initial results indicates
      marginal to good inhibition for the growth of tumor cells for several cell lines,
      which shows the potential of these class of compound towards anticancer
      application.

PMID- 21887798
TI  - Synthesis and free radical scavenging activity of coumarin derivatives containing
      a 2-methylbenzothiazoline motif.
AB  - Coumarin and benzothiazole scaffolds can be found in a number of natural or
      synthetic antioxidants. In an effort to develop a novel radical scavenger and
      potential antioxidant, a series of coumarin derivatives containing 2
      methylbenzothiazoline motif and related compounds was synthesized and evaluated
      for their DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS(*+) (2,2'-azinobis(3
      ethylbenzothiazoline-6-sulfonic acid) radicals scavenging activities. Among them,
      7-hydroxy-3-(2-methyl-2,3-dihydrobenzo[d]thiazol-2-yl)-2H-chromen-2-one (3e) has
      shown a significant free radical scavenging activity. From the structure-activity
      point of view, it was found that phenolic coumarin ring and benzothiazoline
      moiety in target compounds may contribute to the scavenging activity against free
      radicals.

PMID- 21887799
TI  - Evaluation of anti-inflammatory, anti-nociceptive, and anti-ulcerogenic
      activities of novel synthesized thiazolyl and pyrrolyl steroids.
AB  - Developing new therapeutic agents that can overcome gastrointestinal injury and
      at the same time could lead to an enhanced anti-inflammatory effect becomes an
      urgent need for inflammation patients. Thiazolyl and pyrrolyl steroids were
      synthesized via straight forward and efficient methods and their structures were
      established based on their correct elemental analysis and compatible IR, (1) H
      NMR, (13) C-NMR, and mass spectral data. The dihydrothiazolyl
      hydrazonoprogesterone 12 and the aminopyrrolylprogesterone 16a showed anti
      inflammatory, antinociceptive, and anti-ulcerogenic activity with various
      intensities. Edema were significantly reduced by both doses of tested compounds
      (25 and 50 mg/kg) at 2, 3, and 4 h post-carrageenan. The high dose of compound
      16a was the most effective in alleviating thermal pain. Gastric mucosal lesions,
      caused in the rats by the administration of ethanol or indomethacin (IND), were
      significantly inhibited by each of the two tested compounds. These results
      provide a unique opportunity to develop new anti-inflammatory drugs which devoid
      the ulcerogenic liabilities associated with currently marketed drugs.

PMID- 21887800
TI  - Synthesis and anti-bacterial activity of some heterocyclic chalcone derivatives
      bearing thiofuran, furan, and quinoline moieties.
AB  - 36 Novel heterocyclic chalcone derivatives were synthesized and tested for their
      anti-bacterial activity. Some compounds presented good anti-microbial activities
      against Gram-positive bacteria (including the multidrug-resistant clinical
      isolates). This class of compounds presented high potency against Streptococcus
      mutans, among which the derivatives F2 with an MIC of 2 ug/mL was as active as
      the standard drug (norfloxacin) and less active than oxacillin. All the compounds
      did not inhibit the growth of Gram-negative bacteria (Escherichia coli CCARM 1924
      or Escherichia coli CCARM 1356) at 64 ug/mL.

PMID- 21887801
TI  - N-Acetyl-5-arylalkoxytryptamine analogs: probing the melatonin receptors for
      MT(1) -selectivity.
AB  - A series of melatonin analogs obtained by the replacement of the ether methyl
      group with larger arylalkyl and aryloxyalkyl substituents was prepared in order
      to probe the melatonin receptors for MT(1) -selectivity. The most MT(1) 
      selective agents 11 and 15 were substituted with a Ph(CH(2) )(3)  or a PhO(CH(2)
      )(3)  group. Compounds 11 and 15 displayed 11.5-fold and 11-fold higher affinity
      for the MT(1)  receptors than for the MT(2)  subtype. Interestingly, in our
      binding assay 11 and 15 have shown considerably higher MT(1) -affinity and
      selectivity than the reference ligand, the dimeric agomelatine 1a.

PMID- 21887802
TI  - Synthesis and cytotoxicity evaluation of novel podophyllotoxin derivatives.
AB  - Seven benzylamino derivatives of podophyllotoxin 8a-8g were synthesized and their
      chemical structures were confirmed by IR, 1H-NMR, (13)C-NMR and ESI-MS spectral
      analyses. Their abilities to inhibit the growth of cancer cells A549, HCT-116 and
      HepG2, were investigated by MTT assay. Compound 8b possessed the highest
      cytotoxicity on cancer cell lines with average IC(50) values of 3.8 uM. All we
      synthetic compounds were cytotoxic against three cancer cell lines at the
      micromolar range, indicating podophyllotoxin derivatives with structural
      modification of benzylamino possess potent antitumor activity.

PMID- 21887804
TI  - A randomized, double-blind, placebo-controlled study to evaluate the efficacy and
      tolerability of Fufang Danshen (Salvia miltiorrhiza) as add-on antihypertensive
      therapy in Taiwanese patients with uncontrolled hypertension.
AB  - Hypertension generally requires the use of a combination therapy to achieve the
      satisfactory control of blood pressure. A traditional Chinese herb, Danshen
      (Salvia miltiorrhiza), has been shown to have cardioprotective effects in animals
      and humans. The study investigated the add-on effect of Fufang Danshen extract
      capsule in Taiwanese hypertensive patients with uncontrolled blood pressure. This
      was a double-blind, placebo-controlled, randomized, single-center study clinical
      trial. Fifty-five patients with uncontrolled mild to moderate hypertension were
      enrolled under current conventional antihypertensive treatment, randomized
      equally to receive a Fufang Danshen capsule (formula mixture) 1000 mg twice-daily
      or a placebo capsule for 12 weeks. Primary endpoints were the control rate and
      the response rate. By ITT analysis at week 12, the control rates were 25.5% in
      the Fufang Danshen group and 7.3% in the control group (p = 0.016). The response
      rates were 45.6% in the Fufang Danshen group and 38.2% in the placebo group (p =
      0.946). A significant reduction of systolic blood pressure at week 12 was noted
      in the Fufang Danshen group compared with the placebo group (13.8 vs 4.2 mmHg, p
      = 0.005). A decrease of pulse rate was also noted in the Fufang Danshen group (-
      3.2 vs +2.7/min, p = 0.027). Adverse events were not statistically different
      between the two groups. It was concluded that Fufang Danshen (Salvia
      miltiorrhiza) extract reduced systolic blood pressure and pulse rate, and was
      well tolerated in patients with hypertension.

PMID- 21887805
TI  - Baicalin down-regulates the expression of macrophage migration inhibitory factor
      (MIF) effectively for rats with ulcerative colitis.
AB  - The purpose of this study was to investigate whether baicalin, a Chinese herbal
      extract, down-regulates the expression of macrophage migration inhibitory factor
      (MIF), an inflammatory factor that regulates the function of macrophages (MPhi),
      in rats with trinitrobenzene sulphonic acid (TNBS)-induced ulcerative colitis
      (UC). The results showed that baicalin simultaneously down-regulated the
      expression of MIF, the quantity of MPhis and the amount of MPhi-related
      cytokines, including macrophage chemotactic factor-1 (MCP-1, CCL2) and macrophage
      inflammatory protein-3alpha (MIP-3alpha, CCL20), in rats with UC. There was no
      statistical difference between baicailin and mesalazine in down-regulating the
      expression of MIF. Our study demonstrated that baicalin, an inexpensive but
      effective monomer, could be a new and alternative pharmaceutical for UC.

PMID- 21887806
TI  - Antiinflammatory activities of Hungarian Stachys species and their iridoids.
AB  - The antiinflammatory activities of aqueous extracts prepared from the aerial
      parts of ten Hungarian Stachys species were investigated in vivo in the
      carrageenan-induced paw oedema test after intraperitoneal and oral administration
      to rats. Some of the extracts were found to display significant antiphlogistic
      effects when administered intraperitoneally and orally; in particular, the
      extracts of S. alpina, S. germanica, S. officinalis and S. recta demonstrated
      high activity following intraperitoneal administration. At the same dose of 5.0
      mg/kg, these extracts exhibited similar or greater potency than that of the
      positive control diclofenac-Na. The main iridoids present in the investigated
      extracts, ajugoside, aucubin, acetylharpagide, harpagide and harpagoside, were
      also assayed in the same test, and high dose-dependent antiphlogistic effects
      were recorded for aucubin and harpagoside. These results led to the conclusion
      that most probably iridoids are responsible for the antiinflammatory effect of
      Stachys species, but other active constituents or their synergism must also be
      implicated in the antiinflammatory effect.

PMID- 21887807
TI  - The effect of herbal extract (EstroG-100) on pre-, peri- and post-menopausal
      women: a randomized double-blind, placebo-controlled study.
AB  - This clinical research study was designed to evaluate the efficacy of a new
      herbal product, EstroG-100, containing a mixture of standardized extracts of
      Cynanchum wilfordii, Phlomis umbrosa and Angelica gigas, on menopausal symptoms.
      This randomized double-blind, placebo-controlled trial was performed for 12 weeks
      with 64 pre-, peri- and postmenopausal White Hispanic, White non-Hispanic and
      African American women who were randomly allocated to either the EstroG-100 group
      (n = 31) or the placebo group (n =  33). Primary end-points were the mean change
      in scores of the Kupperman menopause index (KMI) that evaluates 11 symptoms, and
      the mean change in scores of vaginal dryness. The mean KMI score was
      significantly reduced in the EstroG-100 group from 29.5 +/- 7.4 at baseline to
      11.3 +/- 5.8 (p < 0.01) compared with change of the placebo group (29.2 +/- 6.6
      at baseline vs 23.7 +/- 7.7 at week 12). The constituting symptoms of vasomotor,
      paresthesia, insomnia, nervousness, melancholia, vertigo, fatigue and rheumatic
      pain were significantly improved in the EstroG-100 group in comparison with the
      placebo group (p < 0.05). Statistically significant improvement in vaginal
      dryness in the EstroG-100 group was also observed compared with that of the
      placebo group (p < 0.05). In conclusion, EstroG-100 significantly improved the
      menopausal symptoms of pre-, peri- and post-menopausal women without weight gain
      or any serious side effects.

PMID- 21887808
TI  - Evaluation of antioxidant activity and antiproliferative effect of fruit juices
      enriched with Pycnogenol(r) in colon carcinoma cells. The effect of in vitro
      gastrointestinal digestion.
AB  - The aim of this study was to examine the effect of in vitro gastrointestinal
      digestion on the antioxidant and antiproliferative effect of fruit juices
      enriched with Pycnogenol(r) (0.5 g/L) on a colon carcinoma cell line (Caco-2).
      The total phenolic concentration (TPC), antioxidant activity and inhibition cell
      growth were studied in fresh and digested pineapple juice and red fruits juice
      (both enriched with pine bark extract and not). After in vitro digestion the
      level of detectable phenolic compounds (expressed as gallic acid equivalent) was
      higher in both pineapple and red fruits juices enriched with Pycnogenol(r) than
      in non-enriched commercial juices (155.6 mg/100 mL vs 94.6 mg/100 mL and 478.5
      mg/100 mL vs 406.9 mg/100 mL, respectively). Increased antioxidant activity
      (measured by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and
      oxygen radical absorbance capacity assay (ORAC) methods) was observed in digested
      enriched juices with respect to the same samples before digestion. Pycnogenol(r)
      enrichment led to a high antiproliferative effect between 24 and 72 h of
      incubation with undigested pineapple juice compared with the non-enriched juice.
      It can be concluded that enrichment of fruit juices with Pycnogenol(r) provides a
      source of phenolic compounds with high stability to in vitro gastrointestinal
      conditions; however, the antioxidant properties of fruit juices were affected to
      a different extent.

PMID- 21887809
TI  - A Markov model to estimate Salmonella morbidity, mortality, illness duration, and
      cost.
AB  - Approximately 690000-1790000 Salmonella cases, 20000 hospitalizations, and 400
      deaths occur in the USA annually, costing approximately $2.6bn. Existing models
      estimate morbidity, mortality, and cost solely from incidence. They do not
      estimate illness duration or use time as an independent cost predictor. Existing
      models may underestimate physician visits, hospitalizations, deaths, and
      associated costs. We developed a Markov chain Monte Carlo model to estimate
      illness duration, physician/emergency room visits, inpatient hospitalizations,
      mortality, and resultant costs for a given Salmonella incidence. Interested
      parties include society, third-party payers, health providers, federal, state and
      local governments, businesses, and individual patients and their families. The
      marginal approach estimates individual disease behavior for every patient,
      explicitly estimates disease duration and calculates separate time-dependent
      costs. The aggregate approach is a Markov equivalent of the existing models; it
      assumes average disease behavior and cost for a given morbidity/mortality.
      Transition probabilities were drawn from a meta-analysis of 53 Salmonella
      studies. Both approaches were tested using the 1993 Salmonella typhimurium
      outbreak in Gideon, Missouri. This protocol can be applied to estimate morbidity,
      mortality and cost of specific outbreaks, provide better national Salmonella
      burden estimates, and estimate the benefits of reducing Salmonella risk.

PMID- 21887810
TI  - When do fat taxes increase consumer welfare?
AB  - Previous analyses of fat taxes have generally worked within an empirical
      framework in which it is difficult to determine whether consumers benefit from
      the policy. This note outlines on simple means to determine whether consumers
      benefit from a fat tax by comparing the ratio of expenditures on the taxed good
      to the weight effect of the tax against the individual's willingness to pay for a
      one-pound weight reduction. Our empirical calculations suggest that an individual
      would have to be willing to pay about $1500 to reduce weight by one pound for a
      tax on sugary beverages to be welfare enhancing. The results suggest either that
      a soda tax is very unlikely to increase individual consumer welfare or that the
      policy must be justified on some other grounds that abandon standard rationality
      assumptions.

PMID- 21887811
TI  - Evaluating the effectiveness and efficacy of unguided internet-based self-help
      intervention for the prevention of depression: a randomized controlled trial.
AB  - The Internet has the potential to increase the capacity and accessibility of
      mental health services. This study aimed to investigate whether an unguided
      Internet-based self-help intervention delivered without human support or guidance
      can reduce symptoms of depression in young people at risk of depression. The
      study also aimed to explore the usage of such sites in a real-life setting, to
      estimate the effects of the intervention for those who received a meaningful
      intervention dose and to evaluate user satisfaction. Young adults were recruited
      by means of a screening survey sent to all students at the University of Tromso.
      Of those responding to the survey, 163 students (mean age 28.2 years) with
      elevated psychological distress were recruited to the trial and randomized to an
      Internet intervention condition or the waiting list control group. The Internet
      condition comprised a depression information website and a self-help Web
      application delivering automated cognitive behavioural therapy. The participants
      in the waiting list condition were free to access formal or informal help as
      usual. Two-thirds of the users who completed the trial initially reported an
      unmet need for help. The findings demonstrated that an unguided intervention was
      effective in reducing symptoms of depression and negative thoughts and in
      increasing depression literacy in young adults. Significant improvements were
      found at 2-month follow up. Internet-based interventions can be effective without
      tracking and thus constitute a minimal cost intervention for reaching a large
      number of people. User satisfaction among participants was high.

PMID- 21887812
TI  - Bipolar vulnerability and extreme appraisals of internal states: a computerized
      ratings study.
AB  - A recent integrative cognitive model proposed that multiple, extreme,
      personalized, positive and negative appraisals of internal states predispose to
      maintain and exacerbate bipolar symptoms. This study aimed to directly assess
      conviction in a range of positive and negative appraisals of internal states
      suggested by the model, by using a laboratory-based computerized task. In a
      student sample (n = 68), a history of hypomania was associated with more positive
      and less negative appraisals of internal states, and a history of depression was
      associated with more negative appraisals and less positive appraisals of internal
      states. The sample was then split into three groups for comparison: bipolar risk
      (n = 18), depression risk (n = 20) and controls (n  = 30). Relative to controls,
      the bipolar risk group made more extreme ratings of catastrophic appraisals of
      low activation states and tended to make more extreme ratings of appraisals of
      high activation states. The depression risk group scored higher on a range of
      negative appraisals of low activation states. These findings provide tentative
      support for the role of both positive and negative, extreme, personalized
      appraisals of internal states in hypomania and depression.

PMID- 21887813
TI  - Hypomanic personality, stability of self-esteem and response styles to negative
      mood.
AB  - OBJECTIVES: This paper aims to study dysfunctional self-schematic processes,
      abnormal coping styles, over-responsiveness to reward stimuli (indicative of an
      over-sensitive behavioural activation system) and stability of self-esteem in
      relation to subclinical hypomania. DESIGN: Three cross-sectional studies were
      conducted on selected students on the basis of their scores on the Hypomanic
      Personality Scale (HPS) (study 1) and on elevated HPS and Dysfunctional Attitude
      Scale scores (studies 2 and 3). METHODS: In studies 1 and 2, participants
      completed questionnaires and kept a self-esteem diary for 6 days. In study 3, the
      experience sampling method was used to assess momentary self-esteem, emotion and
      use of different coping styles over a 6-day period. RESULTS: Study 1 demonstrated
      that hypomanic traits are associated with high fluctuations in self-esteem. In
      study 2, high scores on both the HPS and the Dysfunctional Attitude Scale, but
      not the HPS alone, were associated with bipolar spectrum symptoms. These
      participants showed more evidence of alcohol and substance abuse, greater self
      esteem fluctuation and dysfunctional coping styles (rumination and risk-taking)
      compared with controls. Changes in self-esteem were related to the use of these
      strategies. CONCLUSIONS: Vulnerability to bipolar disorder is associated with a
      combination of depression-related and reward-related processes.

PMID- 21887814
TI  - Estrogen-like response of perfluorooctyl iodide in male medaka (Oryzias latipes)
      based on hepatic vitellogenin induction.
AB  - Using the in vivo male medaka model, we investigated the estrogen-like response
      of perfluorooctyl iodide (PFOI) which is a potential source of perfluorinated
      carboxylic acids. Using real-time quantitative polymerase chain reaction, the
      expression levels of related estrogenic genes including estrogenic receptor alpha
      (ERalpha), ERbeta, vitellogenin I (VTG I), and VTG II in the livers of male
      medaka exposed to PFOI were analyzed. The results showed that PFOI upregulated
      the expression levels of the tested genes in a dose-dependent manner. VTG protein
      levels increased in both dose- and time-dependent manners due to PFOI exposure.
      The results suggested that PFOI is a potential estrogenic compound.

PMID- 21887815
TI  - Protective effects of vitamin E and selenium against dimethoate-induced
      cardiotoxicity in vivo: biochemical and histological studies.
AB  - There is considerable interest in the study of free radical-mediated damage to
      biological systems due to pesticide exposure. However, there is a lack of
      consensus as to which determinations are best used to quantify future risks
      arising from xenobiotic exposure and natural antioxidant interventions. Our study
      investigated the potential ability of selenium and/or vitamin E, used as
      nutritional supplements, to alleviate cardiotoxicity induced by dimethoate.
      Female Wistar rats were exposed for 30 days either to dimethoate (0.2 g L-1 of
      drinking water), dimethoate+selenium (0.5 mg kg-1 of diet), dimethoate+vitamin E
      (100 mg kg-1 of diet), or dimethoate+selenium+vitamin E. The exposure of rats to
      dimethoate promoted oxidative stress with a rise in malondialdehyde, advanced
      protein oxidation, and protein carbonyl levels. An increase of glutathione
      peroxidase, superoxide dismutase, and catalase activities was also noted. A fall
      in acetylcholinesterase and Na+ K+-ATPase activities, glutathione, nonprotein
      thiols, vitamins C and E levels was observed. Plasma levels of cholesterol,
      triglycerides, and low density lipoprotein-cholesterol increased and those of
      high density lipoprotein-cholesterol decreased. Coadministration of selenium or
      vitamin E to the diet of dimethoate-treated rats ameliorated the biochemical
      parameters cited above. The histopathological findings confirmed the biochemical
      results and the potential protective effects of selenium and vitamin E against
      cardiotoxicity induced by dimethoate.

PMID- 21887816
TI  - Classification of polycyclic aromatic hydrocarbons based on mutagenicity in lung
      tissue through DNA microarray.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants
      produced in the combustion of organic matter. Exposure to PAHs raises the risk of
      lung cancer and inflammatory and allergic disorders such as asthma. DNA
      microarray technologies have been applied to research on toxicogenomics in the
      recent years. To evaluate the mutagenicity of PAHs and constituents of
      environmental pollutants in lung tissue, including metabolic activation, human
      alveolar epithelial type II cells (A549) were treated with nonmutagenic PAH
      pyrene and with the mutagenic PAHs benzo-[a]-pyrene, 1-nitropyrene, or 1,8
      dinitropyrene. Comparison of genome-wide microarray expression profiles between a
      nonmutagenic and a mutagenic PAH-treated group revealed that xenobiotic response
      genes such as CYP1B1 were commonly upregulated in two groups and that DNA damage
      induced genes, especially p53-downstream genes such as p21 (CDKN1A) were
      upregulated only in the mutagenic PAH-treated group. Pretreatment with cytochrome
      P450 inhibitor alpha-naphthoflavone or p53 inhibitor pifithrin-alpha inhibited
      the benzo-[a]-pyrene-induced p21 expression. These data suggest that when PAHs
      enter the cells, lung epithelium induces PAH metabolic activating enzymes, and
      then the DNA damages-recognition signal is converged with p53 downstream genes.
      This metabolic activation and DNA damage is induced in lung epithelium, and the
      mutagenicity of PAHs can be classified by DNA microarray expression profiles.

PMID- 21887817
TI  - Quercetin attenuates lambda cyhalothrin-induced reproductive toxicity in male
      rats.
AB  - The aim of this study was to evaluate the possible protective effects of
      Quercetin (Qe) against oxidative stress induced by lambda cyhalothrin (LTC) in
      reproductive system. Thirty-two male rats were divided into four groups. First
      group was allocated as the control group. Second group was given a Qe alone while
      the third group received a LTC alone. Animals in the fourth group were given a Qe
      with LTC. Caudae epididymis was removed for sperm analysis. Lipid peroxidation
      (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx),
      glutathione-S-transferase (GST), and reduced glutathione (GSH) were determined in
      the testis. Additionally, the different histopathologic changes were observed in
      the testis of animals. LTC exposure significantly increased the abnormal
      morphology and LPO. On the contrary, sperm motility, viability and count, levels
      of GSH, and activities of SOD, CAT, GPx, and GST were significantly decreased
      compared to controls. Qe with LTC offset the decrease in functional sperm
      parameters, antioxidants enzymatic activities, and nonenzymatic antioxidant
      levels when compared with LTC-treated rats. Furthermore, LTC showed irregular
      seminiferous tubules containing only Sertoli cells and Qe with LTC caused regular
      seminiferous tubules showing spermatogenesis at level of spermatocytes. We
      conclude that LTC-induced oxidative stress and functional sperm parameters in
      male rats, and dietary of Qe attenuates the reproductive toxicity of LTC to
      restore the antioxidant system and sperm parameters in male rats.

PMID- 21887818
TI  - Rye bran alkylresorcinols suppress adipocyte lipolysis and hormone-sensitive
      lipase activity.
AB  - The effects of alkylresorcinols (ARs) isolated from rye bran on adipocyte
      lipolysis, hormone-sensitive lipase activity and phosphorylation and on
      phosphorylation of protein kinase A substrates were studied. Preincubation with
      ARs for 18 h suppressed catecholamine-stimulated lipolysis in 3T3-L1 adipocytes.
      Furthermore, phosphorylation of hormone-sensitive lipase (HSL), a key lipase
      responsible for stimulated lipolysis, and phosphorylation of protein kinase A
      substrates, were diminished after preincubation with ARs, whereas HSL protein
      expression was unaltered. ARs were also shown to inhibit HSL activity in an in
      vitro assay.

PMID- 21887819
TI  - Tetrahydrocurcumin is more effective than curcumin in preventing azoxymethane
      induced colon carcinogenesis.
AB  - SCOPE: Tetrahydrocurcumin (THC), a major metabolite of curcumin (CUR), has been
      demonstrated to be anti-cancerogenic and anti-angiogenic and prevents type II
      diabetes. In this present study, we investigated the chemopreventive effects and
      underlying molecular mechanisms of dietary administration of CUR and THC in
      azoxymethane (AOM)-induced colon carcinogenesis in mice. METHODS AND RESULTS: All
      mice were sacrificed at 6 and 23 wk, and colonic tissue was collected and
      examined. We found that dietary administration of both CUR and THC could reduce
      aberrant crypt foci and polyps formation, while THC showed a better inhibitory
      effect than CUR. At the molecular level, results from Western blot analysis and
      immunohistochemistry staining showed that dietary CUR and THC exhibited anti
      inflammatory activity by decreasing the levels of inducible NOS and COX-2 through
      downregulation of ERK1/2 activation. In addition, both dietary CUR and THC
      significantly decreased AOM-induced Wnt-1 and beta-catenin protein expression, as
      well as the phosphorylation of GSK-3beta in colonic tissue. Moreover, dietary
      feeding with CUR and THC markedly reduced the protein level of connexin-43, an
      important molecule of gap junctions, indicating that both CUR and THC might
      interfer with the intercellular communication of crypt cells. CONCLUSION: Taken
      together, these results demonstrated for the first time the in vivo
      chemopreventive efficacy and molecular mechanisms of dietary THC against AOM
      induced colonic tumorigenesis.

PMID- 21887820
TI  - Blueberries reduce pro-inflammatory cytokine TNF-alpha and IL-6 production in
      mouse macrophages by inhibiting NF-kappaB activation and the MAPK pathway.
AB  - Blueberries (BB) have been reported to attenuate atherosclerosis in apoE
      deficient (ApoE(-/-) ) mice. The aim of this study was to evaluate the effects of
      BB in reducing pro-inflammatory cytokine production in mouse macrophages. ApoE(-/
      ) mice were fed AIN-93G diet (CD) or CD formulated to contain 1% freeze-dried BB
      for 5 wk. TNF-alpha and IL-6 were lower in serum of BB-fed mice and TNF-alpha
      expression in aorta was down-regulated with BB feeding. Protein level and mRNA
      expression of TNF-alpha and IL-6 were significantly lower in the peritoneal
      macrophages from mice fed BB without or with LPS or oxLDL stimulation. RAW264.7
      macrophages were treated with polyphenol-enriched extracts made from the sera of
      rats fed CD (SEC) or CD containing 10% BB (SEB). SEB significantly inhibited LPS
      induced mRNA expression and protein levels of TNF-alpha and IL-6. Furthermore,
      SEB inhibited the phosphorylation of IkappaB, NF-kappaB p65, MAPK p38 and JNK.
      All of these are important signaling pathways involved in the production of TNF
      alpha and IL-6.

PMID- 21887821
TI  - Characterization of the Asia Oceania Human Proteome Organisation Membrane
      Proteomics Initiative Standard using SDS-PAGE shotgun proteomics.
AB  - Although there are now multiple methods for the analysis of membrane proteomes,
      there is relatively little systematic characterization of proteomic workflows for
      membrane proteins. The Asia Oceania Human Proteome Organisation (AOHUPO) has
      therefore embarked on a Membrane Proteomics Initiative (MPI) using a large range
      of workflows. Here, we describe the characterization of the MPI mouse liver
      microsomal membrane Standard using SDS-PAGE prior to in-gel tryptic digestion and
      LC-ESI-MS/MS. The Na(2) CO(3)  wash followed by SDS-PAGE prior to in-gel tryptic
      digestion and LC-MS/MS strategy was effective for the detection of membrane
      proteins with 47.1% of the identified proteins being transmembrane proteins. Gene
      Ontology term enrichment analysis showed that biological processes involving
      transport, lipid metabolism, cell communication, cell adhesion, and cellular
      component organization were significantly enriched. Comparison of the present
      data with the previously published reports on mouse liver proteomes confirmed
      that the MPI Standard provides an excellent resource for the analysis of membrane
      proteins in the AOHUPO MPI.

PMID- 21887822
TI  - Proteomic identification of Hsp70 as a new Plk1 substrate in arsenic trioxide
      induced mitotically arrested cells.
AB  - We previously demonstrated that when arsenic trioxide (ATO)-induced mitotically
      arrested HeLa S3 cells (AIMACs) were treated with staurosporine (SSP) the cells
      rapidly exited mitosis. To better define the cellular targets and the underlying
      mechanisms of AIMACs, we applied 2-D DIGE followed by LC-MS/MS analysis and
      showed that SSP induced a significant change in the phosphoproteome of AIMACs.
      Among the proteins whose phosphorylation was modulated by SSP, we identified
      Hsp70, Rad 23B, and eukaryotic translation initiation factor 4B as potentially
      new substrates of polo-like kinase 1 (Plk1), an essential serine/threonine kinase
      with versatile mitotic functions. Since Hsp70 is a stress protein responsible for
      ATO treatment, we further identified Thr(13) , Ser(362) , Ser(631) , and Ser(633)
      on Hsp70 intracellularly phosphorylated in AIMACs by combining TiO(2)  phospho
      peptides enrichment and MS/MS analysis. Using antibody specifically against
      phosph-Ser(631)  Hsp70 and further aided by expression of kinase-dead Plk1 and
      pharmacological inhibition of Plk1, we concluded that Ser(631)  on Hsp70 is
      phosphorylated by Plk1 in AIMACs. By immnuofluorescent staining, we found the
      colocalization of Hsp70 and Plk1 in AIMACs but not in interphase cells. In
      addition, Plk1-mediated phosphorylation of Hsp70 prevented AIMACs from mitotic
      death. Our results reveal that Hsp70 is a novel substrate of Plk1 and that its
      phosphorylation contributes to attenuation of ATO-induced mitotic abnormalities.

PMID- 21887824
TI  - Using side-chain aromatic proton chemical shifts for a quantitative analysis of
      protein structures.

PMID- 21887823
TI  - The dynamics of T cells during persistent Staphylococcus aureus infection: from
      antigen-reactivity to in vivo anergy.
AB  - Staphylococcus aureus is an important human pathogen that can cause long-lasting
      persistent infections. The mechanisms by which persistent infections are
      maintained involve both bacterial escape strategies and modulation of the host
      immune response. So far, the investigations in this area have focused on
      strategies used by S. aureus to persist within the host. Here, we used an
      experimental mouse model to investigate the host response to persistent S. aureus
      infection. Our results demonstrated that T cells, which are critical for
      controlling S. aureus infection, gradually lost their ability to respond to
      antigenic stimulation and entered a state of anergy with the progression of
      infection towards persistence. The T cell hyporesponsiveness was reverted by co
      stimulation with the phorbol ester PMA, an activator of protein kinase C,
      suggesting that a failure in the T cell receptor (TCR)-proximal signalling events
      underlie the hyporesponsive phenotype. The presence of these anergic antigen
      specific T cells may contribute to the failure of the host immune response to
      promote sterilizing immunity during persistent S. aureus infection and also
      offers new possibilities for novel immunotherapeutic approaches.

PMID- 21887825
TI  - DNA-linked nanoparticle building blocks for programmable matter.

PMID- 21887826
TI  - Foldamer-tuned switching kinetics and metastability of [2]rotaxanes.
AB  - Slip sliding away: foldamers can function as modular stoppers to regulate the
      slippage and de-slippage of pseudorotaxanes and the switching kinetics and
      metastability of bistable rotaxanes. By simply changing the solvent or the length
      of the hydrogen-bonded foldamer, the lifetime of the metastable co-conformation
      state can be increased dramatically, from several minutes to as long as several
      days.

PMID- 21887827
TI  - Synthesis of phenanthridinones from N-methoxybenzamides and arenes by multiple
      palladium-catalyzed C-H activation steps at room temperature.
AB  - Many steps make light work: substituted phenanthridinones can be obtained with
      high regioselectivity and in very good yields by palladium-catalyzed cyclization
      reactions of N-methoxybenzamides with arenes. The reaction proceeds through
      multiple oxidative C-H activation and C-C/C-N formation steps in one pot at room
      temperature, and thus provides a simple method for generating bioactive
      phenanthridinones.

PMID- 21887828
TI  - Three-component coupling of arynes and organic bromides.

PMID- 21887829
TI  - Structural features and hydrogen-bond properties of galanthamine and codeine: an
      experimental and theoretical study.
AB  - Structural features of galanthamine and codeine, two allosteric potentiating
      ligands of nicotinic acetylcholine receptors (nAChRs), have been investigated
      through experimental studies in solution by FTIR and NMR spectroscopy and by
      quantum chemical calculations in the isolated state. The infrared spectra
      accumulated in solvents of various polarities show that the intramolecular OH...O
      hydrogen bond in galanthamine is stronger than the corresponding interaction in
      codeine. Molecular electrostatic potential calculations allow rationalisation of
      the experimental trends. NOE measurements on the two ligands in the same solvent
      range show significant differences. In apolar solvents, the NMR spectroscopic
      data indicate the occurrence of CH...O hydrogen-bond interactions, whereas in the
      more polar solvents, a trans orientation of the methoxy group with respect to the
      furanyl oxygen atom is favoured. A natural bond orbital (NBO) analysis provides
      evidence that these stabilising interactions originate in the hyperconjugation
      between the lone pairs of the furanyl oxygen atoms, n(O), and the methoxy
      antibonding sigma*(C-H) orbitals within the two molecules. Despite the strong
      structural similarities between the two allosteric modulators, FTIR equilibrium
      constants measurements of hydrogen-bond complexation combined with quantum
      chemistry calculations point out the significant increase of hydrogen-bond
      accepting strength of galanthamine relative to codeine. This increase is mainly
      assignable to the stronger hydrogen-bond basicity of the hydroxyl group, and to a
      lesser extent to the higher hydrogen-bond accepting strength of the amino
      nitrogen of galanthamine in comparison with the corresponding groups of codeine.
      An analysis of the interactions that occur between the two ligands and
      acetylcholine esterase (AChE) suggests significant differences with Trp84, a key
      component of the AChE catalytic active site. In contrast, both ligands appear to
      interact similarly with acetylcholine binding protein (AChBP).

PMID- 21887831
TI  - Stereoselective synthesis of trisubstituted olefins by a directed allylic
      substitution strategy.
AB  - New methodology for the stereoselective synthesis of trisubstituted olefins is
      presented. The use of ortho-diphenylphosphanyl benzoate (o-DPPB) as a directing
      leaving group for copper-mediated allylic substitution with Grignard reagents
      allowed for the stereoselective construction of a wide range of E olefins,
      without the need for an adjacent electron-withdrawing group. Our modular three
      step approach toward trisubstituted alkenes commenced with geminal alpha
      methylene aldehydes. Addition of an organometallic reagent and introduction of
      the o-DPPB group by esterification was followed by the o-DPPB-directed copper
      mediated allylic substitution with a Grignard reagent to furnish stereodefined
      trisubstituted olefins. Additionally, incorporation of a stereocenter from the
      chiral pool allowed the preparation of an enantiomerically pure olefin that bore
      three alkyl substituents in high E/Z selectivity.

PMID- 21887830
TI  - Guest-release control in enzyme-sensitive, amphiphilic-dendrimer-based
      nanoparticles through photochemical crosslinking.
AB  - Stimuli sensitive, facially amphiphilic dendrimers have been synthesized and
      their enzyme-responsive nature has been determined with dual fluorescence
      responses of both covalently conjugated and non-covalently bound reporter units.
      These dual responses are correlated to ascertain the effect of enzymatic action
      on micellar aggregates and the consequential guest release. The release of the
      guest molecule is conveniently tuned by stabilizing the micellar aggregates
      through photochemical crosslinking of hydrophobic coumarin units. This photo
      crosslinking is also utilized as a tool to investigate the mode of enzyme
      substrate interaction in the context of aggregate-monomer equilibrium.

PMID- 21887832
TI  - Conjugated asymmetric donor-substituted 1,3,5-triazines: new host materials for
      blue phosphorescent organic light-emitting diodes.
AB  - Conjugated asymmetric donor-substituted 1,3,5-triazines (ADTs) have been
      synthesized by nucleophilic substitution of organolithium catalyzed by
      [Pd(PPh(3))(4)]. Theoretical and experimental investigations show that ADTs
      possess high solubility and thermostability, high fluorescent quantum yield
      (35%), low HOMO (-6.0 eV) and LUMO (-2.8 eV), and high triplet energy (E(T), 3.0
      eV) according to the different substitution pattern of triazine. The application
      as host materials for blue PHOLEDs yielded a maximum current efficiency of 20.9
      cd A(-1), a maximum external quantum efficiency of 9.8%, and a brightness of 9671
      cd m(-2) at 5.4 V, making ADTs good candidates for optoelectronic devices.

PMID- 21887833
TI  - Surface-modified protein microspheres capture amyloid-beta and inhibit its
      aggregation and toxicity.
AB  - The biocompatible and biodegradable properties of protein microspheres and the
      recent advances in their preparation have generated considerable interest of
      utilizing these core-shell structures for drug delivery and diagnostic
      applications. However, effective targeting of protein microspheres to desirable
      cells or loci still remains a challenge. Here, we describe for the first time a
      facile one-pot sonochemical approach for covalent modification of protein
      microspheres made from serum albumin; the surface of which is covalently
      decorated with a short recognition peptide to target amyloid-beta (Abeta) as the
      main pathogenic protein in Alzheimer's disease (AD). The microspheres were
      characterized for their morphology, size, and entrapment efficacy by electron
      microscopy, dynamic light scattering and confocal microscopy. Fluorescence
      activated cell-sorting analysis and Thioflavin-T binding assay demonstrated that
      the conjugated microspheres bind with high affinity and selectivity to Abeta,
      sequester it from the medium and reduce its aggregation. Upon incubation with
      Abeta, the microspheres induced formation of amorphous aggregates on their
      surface with no apparent fibrillar structure. Moreover, the microspheres directly
      reduced the Abeta-induced toxicity toward neuron like PC12 cells. The conjugated
      microspheres are smaller than unmodified microspheres and remained stable
      throughout the incubation under physiological conditions.

PMID- 21887834
TI  - Gas-phase radical-radical reaction dynamics of O(3P)+C2H3->C2H2+OH.

PMID- 21887835
TI  - WaterLOGSY NMR experiments in conjunction with molecular-dynamics simulations
      identify immobilized water molecules that bridge peptide mimic MDWNMHAA to
      anticarbohydrate antibody SYA/J6.
AB  - X-ray crystallographic data of the carbohydrate mimic MDWNMHAA when bound to an
      anti-Shigella flexneri Y mAb SYA/J6 indicate the immobilization of water
      molecules, that is, the presence of "bound" waters, in the active site. Water
      Ligand Observed via Gradient Spectroscopy (WaterLOGSY) was used in conjunction
      with saturation transfer difference (STD)-NMR spectroscopy to probe the existence
      of immobilized water molecules in the complex of MDWNMHAA 1 bound to mAb SYA/J6.
      Molecular dynamics simulations using the ZymeCAD Molecular Dynamics platform were
      then used to specify the likely locations of these water molecules. Of note,
      those waters involved in providing complementarity between the peptide and mAb
      SYA/J6 remained throughout the course of the simulation. Together, the
      experimental and computational protocols have been used to identify the bound
      water molecules present in the antibody-peptide complex.

PMID- 21887836
TI  - An efficient, overall [4+1] cycloaddition of 1,3-dienes and nitrene precursors.
AB  - Intermolecular cycloadditions of conjugated dienes and nitrene precursors usually
      produce aziridines. A generally useful method was lacking to directly provide the
      [4+1] cycloadducts, 3-pyrrolines. We have realized this transformation by using
      an uniquely active catalyst, copper(II) 1,1,1,5,5,5-hexafluoroacetylacetonate
      ([Cu(hfacac)(2)]). The method is applicable to a wide array of dienes with good
      yields. When 1,4-disubstituted dienes are used as substrates, good-to-excellent
      cis or trans selectivity can be obtained. Interestingly, the cis or trans
      preference depends on the nature of the substituents, rather than diene geometry.
      Mechanistic studies reveal that the [4+1] cycloaddition proceeds through diene
      aziridination and subsequent ring expansion. Among common copper catalysts, only
      [Cu(hfacac)(2)] can efficiently catalyze both steps, which explains the unique
      efficiency of the catalyst.

PMID- 21887837
TI  - Bioelectrochemically active infinite coordination polymer nanoparticles: one-pot
      synthesis and biosensing property.

PMID- 21887838
TI  - One-pot synthesis of chiral aziridines by a domino reaction by using
      desulfonylative formation on the N-tosyl imine of chloroacetaldehyde with an
      asymmetric Mannich reaction as a key step.

PMID- 21887839
TI  - An effective method to introduce carbon acid functionality: 2,2
      bis(trifluoromethanesulfonyl)ethylation reaction of arenes.

PMID- 21887840
TI  - An acyloxymethyl ketone-based probe to monitor the activity of
      glutathionylspermidine amidase in Escherichia coli.
AB  - Cellular redox conditions affect Gsp amidase activity in Escherichia coli. Guided
      by the structure and catalytic mechanism of the amidase, we designed and
      synthesized an acyloxymethyl ketone-based activity probe containing a biotin
      handle. This probe was used to monitor Gsp amidase activity in E. coli lysates
      that had been subjected to oxidative or methylglyoxal-induced stress.

PMID- 21887841
TI  - Highly fluorescent 5-(5,6-dimethoxybenzothiazol-2-yl)-2'-deoxyuridine 5'
      triphosphate as an efficient substrate for DNA polymerases.
AB  - We herein describe the synthesis of fluorescent 5-(5,6-dimethoxybenzothiazol-2
      yl)-2'-deoxyuridine 5'-triphosphate (d(bt)UTP) and primer extension reactions
      using d(bt)UTP. We also carried out primer extension reactions using the (bt)U
      template. B family DNA polymerases, such as KOD, Deep Vent (exo-), and 9 degrees
      N(m) DNA polymerases, were effective for elongation with d(bt)UTP. Deep Vent (exo
      ) and KOD DNA polymerases have excellent fidelity for incorporating d(bt)UTP only
      at the site opposite the adenine template and only dATP when using the (bt)U
      template. Therefore, d(bt)UTP is an excellent fluorescent nucleotide that can be
      incorporated into DNA by DNA polymerases.

PMID- 21887842
TI  - Photon density wave spectroscopy for dilution-free sizing of highly concentrated
      nanoparticles during starved-feed polymerization.

PMID- 21887843
TI  - Pathogenic mutations of TGFBI and CHST6 genes in Chinese patients with Avellino,
      lattice, and macular corneal dystrophies.
AB  - OBJECTIVE: To investigate gene mutations associated with three different types of
      corneal dystrophies (CDs), and to establish a phenotype-genotype correlation.
      METHODS: Two patients with Avellino corneal dystrophy (ACD), four patients with
      lattice corneal dystrophy type I (LCD I) from one family, and three patients with
      macular corneal dystrophy type I (MCD I) were subjected to both clinical and
      genetic examinations. Slit lamp examination was performed for all the subjects to
      assess their corneal phenotypes. Genomic DNA was extracted from peripheral blood
      leukocytes. The coding regions of the human transforming growth factor beta
      induced (TGFBI) gene and carbohydrate sulfotransferase 6 (CHST6) gene were
      amplified by polymerase chain reaction (PCR) and subjected to direct sequencing.
      DNA samples from 50 healthy volunteers were used as controls. RESULTS: Clinical
      examination showed three different phenotypes of CDs. Genetic examination
      identified that two ACD subjects were associated with homozygous R124H mutation
      of TGFBI, and four LCD I subjects were all associated with R124C heterozygous
      mutation. One MCD I subject was associated with a novel S51X homozygous mutation
      in CHST6, while the other two MCD I subjects harbored a previously reported W232X
      homozygous mutation. CONCLUSIONS: Our study highlights the prevalence of codon
      124 mutations in the TGFBI gene among the Chinese ACD and LCD I patients.
      Moreover, we found a novel mutation among MCD I patients.

PMID- 21887844
TI  - Clinical heterogeneity in patients with early-stage Parkinson's disease: a
      cluster analysis.
AB  - The aim of this study was to investigate the clinical heterogeneity of
      Parkinson's disease (PD) among a cohort of Chinese patients in early stages.
      Clinical data on demographics, motor variables, motor phenotypes, disease
      progression, global cognitive function, depression, apathy, sleep quality,
      constipation, fatigue, and L-dopa complications were collected from 138 Chinese
      PD subjects in early stages (Hoehn and Yahr stages 1-3). The PD subject subtypes
      were classified using k-means cluster analysis according to the clinical data
      from five- to three-cluster consecutively. Kappa statistical analysis was
      performed to evaluate the consistency among different subtype solutions. The
      cluster analysis indicated four main subtypes: the non-tremor dominant subtype
      (NTD, n=28, 20.3%), rapid disease progression subtype (RDP, n=7, 5.1%), young
      onset subtype (YO, n=50, 36.2%), and tremor dominant subtype (TD, n=53, 38.4%).
      Overall, 78.3% (108/138) of subjects were always classified between the same
      three groups (52 always in TD, 7 in RDP, and 49 in NTD), and 98.6% (136/138)
      between five- and four-cluster solutions. However, subjects classified as NTD in
      the four-cluster analysis were dispersed into different subtypes in the three
      cluster analysis, with low concordance between four- and three-cluster solutions
      (kappa value=-0.139, P=0.001). This study defines clinical heterogeneity of PD
      patients in early stages using a data-driven approach. The subtypes generated by
      the four-cluster solution appear to exhibit ideal internal cohesion and external
      isolation.

PMID- 21887845
TI  - Changes of paired-pulse evoked responses during the development of epileptic
      activity in the hippocampus.
AB  - Dysfunction of inhibitory synaptic transmission can destroy the balance between
      excitatory and inhibitory synaptic inputs in neurons, thereby inducing epileptic
      activity. The aim of the paper is to investigate the effects of successive
      excitatory inputs on the epileptic activity induced in the absence of
      inhibitions. Paired-pulse orthodromic and antidromic stimulations were used to
      test the changes in the evoked responses in the hippocampus. Picrotoxin (PTX),
      gamma-aminobutyric acid (GABA) type A (GABA(A)) receptor antagonist, was added to
      block the inhibitory synaptic transmission and to establish the epileptic model.
      Extracellular evoked population spike (PS) was recorded in the CA1 region of the
      hippocampus. The results showed that the application of PTX induced a biphasic
      change in the paired-pulse ratio of PS amplitude. A short latency increase of the
      second PS (PS2) was later followed by a reappearance of PS2 depression. This type
      of depression was observed in both orthodromic and antidromic paired-pulse
      responses, whereas the GABAergic PS2 depression [called paired-pulse depression
      (PPD)] during baseline recordings only appeared in orthodromic-evoked responses.
      In addition, the depression duration at approximately 100 ms was consistent with
      a relative silent period observed within spontaneous burst discharges induced by
      prolonged application of PTX. In conclusion, the neurons may ignore the
      excitatory inputs and intrinsically generate bursts during epileptic activity.
      The depolarization block could be the mechanisms underlying the PPD in the
      absence of GABA(A) inhibitions. The distinct neuronal responses to stimulations
      during different epileptic stages may implicate the different antiepileptic
      effects of electrical stimulation.

PMID- 21887846
TI  - Hyaluronic acid as a rescue therapy for trinitrobenzene sulfonic acid-induced
      colitis through Cox-2 and PGE2 in a Toll-like receptor 4-dependent way.
AB  - We hypothesized whether systemic administration of high-molecular-weight
      hyaluronic acid (HMW HA) could rescue trinitrobenzene sulfonic acid (TNBS)
      induced colitis through Toll-like receptor 4 (TLR4) signal. C3H/HeN mice and
      C3H/HeJ mice were used. Mice were divided into four groups: control, 50% ethanol
      treatment group, TNBS treatment group, and TNBS plus HA treatment group. The
      weight changes, clinical scores, macroscopic scores, and histological scores were
      recorded. Cyclooxygenase 2 (Cox-2) and prostaglandin E(2) (PGE(2)) expressions
      were measured both in colons and peritoneal macrophages from these mice. HA was a
      rescue therapy for the colitis induced by TNBS only in C3H/HeN mice. The clinical
      score, macroscopic score, and histological score were much lower in C3H/HeN mice
      receiving TNBS plus HA treatment. Cox-2 and PGE(2) expressions only increased in
      C3H/HeN mice. These Cox-2 expressing cells were macrophages. HA can also promote
      the production of Cox-2 and PGE(2) in peritoneal macrophages from C3H/HeN mice.
      Our data demonstrated that HMW HA can rescue TNBS-induced colitis through
      inducing Cox-2 and PGE(2) expressions in a TLR4-dependent way. Macrophages may be
      the effector cells of HMW HA.

PMID- 21887847
TI  - Polyethylenimine-cyclodextrin-tegafur conjugate shows anti-cancer activity and a
      potential for gene delivery.
AB  - Polyethylenimine-cyclodextrin-tegafur (PEI-CyD-tegafur) conjugate was synthesized
      as a novel multifunctional prodrug of tegafur for co-delivery of chemotherapeutic
      agent tegafur and enhanced green fluorescent protein (EGFP) reporter plasmid DNA.
      Conjugation of tegafur to PEI-CyD via chemical linkage was characterized by (1)H
      NMR spectrometry and ultraviolet (UV) spectrometry. PEI-CyD-tegafur was able to
      condense plasmid DNA into complexes of around 150 nm with positive charge at the
      N/P ratio of 25, in accordance with electron microscopy observation of compact
      and monodisperse nanoparticles. The results of in vitro experiments showed
      enhanced cytotoxicity and considerable transfection efficiency in B16F10 cell
      line. Therefore, PEI-CyD-tegafur may have great potential as a co-delivery system
      with anti-cancer activity and potential for gene delivery.

PMID- 21887848
TI  - Age-dependent expression of forkhead box O proteins in the duodenum of rats.
AB  - The O subfamily of forkhead box (FoxO) proteins is the downstream effector of the
      insulin-like growth factor-1/phosphoinositide 3-kinase/protein kinase B (IGF
      1/PI3K/PKB) signal pathway. The objective of the present study was to examine the
      expressions of three members of FoxO proteins, FoxO1, FoxO3a, and FoxO4 in the
      duodenum of Sprague-Dawley rats at different ages. The result demonstrated that
      the expression of FoxO4 in rat duodenum showed an age-dependent manner. At Day
      21, there were no detectable localization and expression of FoxO4 in the
      duodenum, while, at Months 2 and 6, localization and expression of FoxO4 were
      distinct. In addition, FoxO4 staining was primarily concentrated in the cell
      nuclei of the lamina propria around the intestinal gland of the duodenum in 2
      month-old rats, but was not detectable in the same area in 6-month-old rats. Our
      results showed also that although FoxO3a existed in the cytoplasm of the lamina
      propria at a low level at the 2- and 6-month marks, it was still not detectable
      at Day 21. Besides, FoxO1 was not detectable in all parts and stages. Taken
      together, our findings suggested that the cell-specific and age-dependent
      expressional patterns of FoxO4 and FoxO3a proteins in the duodenum play some
      roles in the development and growth performance of the rat duodenum.

PMID- 21887850
TI  - Evaluation of the antioxidant effects of four main theaflavin derivatives through
      chemiluminescence and DNA damage analyses.
AB  - Theaflavins (TFs) are the dimers of a couple of epimerized catechins, which are
      specially formed during black tea fermentation. To explore the differences among
      four main TF derivatives (theaflavin (TF(1)), theaflavin-3-gallate (TF(2)A),
      theaflavin-3'-gallate (TF(2)B), and theaflavin-3,3'-digallate (TF(3))) in
      scavenging reactive oxygen species (ROS) in vitro, their properties of inhibiting
      superoxide, singlet oxygen, hydrogen peroxide, and the hydroxyl radical, and
      their effects on hydroxyl radical-induced DNA oxidative damage were
      systematically analyzed in the present study. The results show that, compared
      with (-)-epigallocatechin gallate (EGCG), TF derivatives were good antioxidants
      for scavenging ROS and preventing the hydroxyl radical-induced DNA damage in
      vitro. TF(3) was the most positive in scavenging hydrogen peroxide and hydroxyl
      radical, and TF(1) suppressed superoxide. Positive antioxidant capacities of
      TF(2)B on singlet oxygen, hydrogen peroxide, hydroxyl radical, and the hydroxyl
      radical-induced DNA damage in vitro were found. The differences between the
      antioxidant capacities of four main TF derivatives in relation to their chemical
      structures were also discussed. We suggest that these activity differences among
      TF derivatives would be beneficial to scavenge different ROS with therapeutic
      potential.

PMID- 21887851
TI  - Effect of three cooking methods on nutrient components and antioxidant capacities
      of bamboo shoot (Phyllostachys praecox C.D. Chu et C.S. Chao).
AB  - Three cooking methods, namely boiling, steaming, and stir-frying for 5 to 10 min,
      were used to evaluate the effect on nutrient components, free amino acids, L
      ascorbic acid, total phenolic contents, and antioxidant capacities of bamboo
      shoots (Phyllostachys praecox). Results showed that boiling and stir-frying had a
      great effect on the nutrient components and they decreased the contents of
      protein, soluble sugar, and ash, and caused a great loss in the total free amino
      acids (decreased by 38.35% and 34.86%, respectively). Significant differences
      (P<0.05) in free amino acids were observed in the samples cooked by different
      methods. Stir-fried bamboo shoots had a high fat content which increased by
      528.57% because of the addition of edible oil. After boiling, the L-ascorbic acid
      and total phenolic contents were significantly reduced, while steaming increased
      total phenolic content by 3.98% and stir-frying well-preserved L-ascorbic acid
      (78.87% of its previous content). Results of the antioxidative property study
      showed that stir-frying could increase antioxidant capacities of bamboo shoots.
      It is concluded that stir-frying is more suitable for bamboo shoots because it
      could obtain the maximum retention of antioxidant capacities.

PMID- 21887849
TI  - Effect of dietary fatty acids on serum parameters, fatty acid compositions, and
      liver histology in Shaoxing laying ducks.
AB  - The effects of different fatty acid (FA) contents in diet on serum parameters, FA
      compositions of eggs and meat, and liver morphological changes were studied in
      Shaoxing laying ducks. A total of 264 ducks at 17 weeks were fed a control diet
      or a diet containing 30 g/kg fish oil (FO), 25 g/kg sunflower oil (SO), or 30
      g/kg palm oil with 20 g/kg beef tallow (PBO). Malondialdehyde (MDA) content in
      the liver and the serum of ducks fed the PBO diet was significantly (P<0.05)
      higher than that of ducks fed the other diets. Triglyceride (TG) and total
      cholesterol (TC) levels were significantly lower (P<0.05) in ducks fed the FO
      diet. Serum TC also was lower in ducks fed the SO diet. Superoxide dismutase
      (SOD) activity was also affected by diets. The contents of polyunsaturated FAs
      (PUFAs) in eggs and meat were significantly higher (P<0.001) in ducks fed the FO
      and SO diets than in ducks fed the control diet. The level of C22:6 (n-3) FA in
      ducks fed the FO diet was significantly higher than that in ducks fed the other
      diets. However, the conversion efficiency of the longer-chain C20:5 (n-3) FA was
      higher than that of C22:6 (n-3). Ducks fed the PBO diet exhibited lipid droplet
      accumulation in the liver. These results demonstrate that a diet enriched with
      different FAs has strong effects on serum lipid levels and the deposition of
      PUFAs into tissue lipids.

PMID- 21887852
TI  - Changes in bacterial community of anthracene bioremediation in municipal solid
      waste composting soil.
AB  - Polycyclic aromatic hydrocarbons (PAHs) are common contaminants in a municipal
      solid waste (MSW) composting site. Knowledge of changes in microbial structure is
      useful to identify particular PAH degraders. However, the microbial community in
      the MSW composting soil and its change associated with prolonged exposure to PAHs
      and subsequent biodegradation remain largely unknown. In this study, anthracene
      was selected as a model compound. The bacterial community structure was
      investigated using terminal restriction fragment length polymorphism (TRFLP) and
      16S rRNA gene clone library analysis. The two bimolecular tools revealed a large
      shift of bacterial community structure after anthracene amendment and subsequent
      biodegradation. Genera Methylophilus, Mesorhizobium, and Terrimonas had potential
      links to anthracene biodegradation, suggesting a consortium playing an active
      role.

PMID- 21887853
TI  - Digital design of scaffold for mandibular defect repair based on tissue
      engineering.
AB  - Mandibular defect occurs more frequently in recent years, and clinical repair
      operations via bone transplantation are difficult to be further improved due to
      some intrinsic flaws. Tissue engineering, which is a hot research field of
      biomedical engineering, provides a new direction for mandibular defect repair. As
      the basis and key part of tissue engineering, scaffolds have been widely and
      deeply studied in regards to the basic theory, as well as the principle of
      biomaterial, structure, design, and fabrication method. However, little research
      is targeted at tissue regeneration for clinic repair operations. Since mandibular
      bone has a special structure, rather than uniform and regular structure in
      existing studies, a methodology based on tissue engineering is proposed for
      mandibular defect repair in this paper. Key steps regarding scaffold digital
      design, such as external shape design and internal microstructure design directly
      based on triangular meshes are discussed in detail. By analyzing the theoretical
      model and the measured data from the test parts fabricated by rapid prototyping,
      the feasibility and effectiveness of the proposed methodology are properly
      verified. More works about mechanical and biological improvements need to be done
      to promote its clinical application in future.

PMID- 21887854
TI  - A tasseled cap transformation for CBERS-02B CCD data.
AB  - The tasseled cap transformation of remote sensing data has been widely used in
      agriculture, forest, ecology, and landscape. In this paper, tasseled cap
      transformation coefficients appropriate for data from a new sensor (China &
      Brazil Earth Resource Satellite (CBERS-02B)) are presented. The first three
      components after transformation captured 98% of the four-band variance, and
      represent the physical characteristics of brightness (coefficients: 0.509, 0.431,
      0.330, and 0.668), greenness (coefficients: -0.494, -0.318, -0.324, and 0.741),
      and blueness (coefficients: 0.581, -0.070, -0.811, and 0.003), respectively. We
      hope these results will enhance the application of CBERS-02B charge-coupled
      device (CCD) data in the areas of agriculture, forest, ecology, and landscape.

PMID- 21887855
TI  - Yokukansan enhances pentobarbital-induced sleep in socially isolated mice:
      possible involvement of GABA(A)-benzodiazepine receptor complex.
AB  - In the present study, we investigated the effect of the Kampo medicine Yokukansan
      (YKS) on pentobarbital-induced sleep in group-housed and socially isolated mice.
      Socially isolated mice showed shorter sleeping time than the group-housed mice.
      YKS (300 mg/kg, p.o.) prolonged the pentobarbital-induced sleeping time in
      socially isolated mice without affecting pentobarbital sleep in group-housed
      mice. The prolongation of sleeping time by YKS was reversed by bicuculline (3
      mg/kg, i.p.) and flumazenil (3 mg/kg, i.p.), but not WAY100635. These findings
      suggest that the GABA(A)-benzodiazepine receptor complex, but not 5-HT(1A)
      receptors, is involved in the reversal effect of YKS on the decrease of
      pentobarbital sleep by social isolation.

PMID- 21887856
TI  - In memory of Dr. Hitoshi Kamiya.

PMID- 21887857
TI  - Widening access to medicine.

PMID- 21887859
TI  - Exercising options.

PMID- 21887858
TI  - Retraction notice to "Curcumin suppresses constitutive activation of AP-1 by
      downregulation of JunD protein in HTLV-1-infected T-cell lines" [Leuk. Res. 30
      (2006) 313-321].

PMID- 21887860
TI  - Nature Reviews Genetics. From the editors.

PMID- 21887861
TI  - Low-dose naltrexone: harnessing the body's own chemistry to treat human ovarian
      cancer.

PMID- 21887862
TI  - Serum bicarbonate as a marker to predict mortality in toxic epidermal necrolysis.
AB  - BACKGROUND: Toxic epidermal necrolysis (TEN) is a rare life-threatening disorder
      characterized by extensive epidermal necrolysis. Its mortality which varies from
      20% to 60% is related to risk factors such as age, extent of epidermal
      detachment, and base deficit. OBJECTIVES: The purpose of this study is to
      investigate the risk factors of mortality in our patients with TEN. PATIENTS AND
      METHODS: From the year 2000 to 2006, the patients with TEN admitted to the
      National Taiwan University Hospital Burn Center were studied retrospectively
      using chart review. Eleven potential risk factors including age, gender,
      underlying disease, malignancy, extent of epidermal detachment, tachycardia,
      serum urea, glucose, base deficit, leucopenia, and intravenous infusion of
      immunoglobulin (IVIG) were analyzed. Patients were grouped into survivors (n 1/4
      11) and nonsurvivors (n 1/4 5) after intensive care treatment. Logistic
      regression was used in multivariate analysis for identifying important predictors
      of mortality. RESULTS: The mean age of the patients with TEN was 58 years, while
      the mean total body surface area of epidermal necrolysis was 66.3%. The overall
      mortality rate was 31.3%. Among the potential risk factors, only serum
      bicarbonate <20 mmol/L was found to have significant association with mortality
      (P 1/4 .0128) in our patients with TEN. The odds of mortality in the patients
      with TEN having serum bicarbonate <20 mmol/L was 40 times higher than those
      without. CONCLUSION: This study has shown that serum bicarbonate <20 mmol/L is
      the most important risk factor of mortality in our patients with TEN and it may
      be used as a marker to predict hospital mortality.

PMID- 21887863
TI  - Extubation of the difficult airway.
AB  - Managing the airway in the intensive care unit (ICU) is complicated by a wide
      array of physiologic factors. Difficult airway may be a consequence of patient's
      anatomy or airway edema developed during the ICU stay and mechanical ventilation.
      The incidence of failed airways and of cardiac arrest related to airway
      instrumentation in the ICU is much higher than that of elective intubations
      performed in the operating room. In this article, we will provide a framework for
      identifying a difficult airway, criteria for safe extubation, as well as review
      the devices that are available for airway management in the ICU. Proficiency in
      identifying a potentially difficult airway and thorough familiarity with
      strategies and techniques of securing the airway are necessary for safe practice
      of critical care medicine

PMID- 21887864
TI  - The lipid A assembly pathway: the work of Christian Raetz.

PMID- 21887865
TI  - Expression of concern.

PMID- 21887866
TI  - A dodecanuclear heterometallic dysprosium-cobalt wheel exhibiting single-molecule
      magnet behaviour.
AB  - A novel dodecanuclear wheel with ten Dy(III) ions and two Co(II) ions bridged by
      four Schiff-base ligands and sixteen acetates represents the highest-nuclearity
      3d-4f example of its type displaying single-molecule magnet behaviour.

PMID- 21887867
TI  - Profile. Wallace F. Chong, Jr., DDS. Going strong after 44 years.

PMID- 21887868
TI  - Magic mouthwash.

PMID- 21887869
TI  - Nicholson's power is unrivalled--so is his responsibility to lead.

PMID- 21887870
TI  - Nicholson: NHS faces 'big problem' if reforms lose pace.

PMID- 21887872
TI  - Legal costs. Negligence claims increasing 10% per year.

PMID- 21887871
TI  - Restructure. PCT clusters to survive as arms of the NHS Commissioning Board as
      new groups form.

PMID- 21887873
TI  - Fighting talk for a year of living dangerously. Interview by Charlotte Santry.

PMID- 21887874
TI  - Under the microscope: pulmonary nontuberculous mycobacteria.

PMID- 21887875
TI  - Workplace bullying too much to handle.

PMID- 21887876
TI  - A personal experience with assisted second stage labor.

PMID- 21887877
TI  - A long second stage in Argentina.

PMID- 21887879
TI  - [Lung cancer-statistics of hospital-based cancer registry data in Japan-].

PMID- 21887880
TI  - Meiotic chromosome pairing and recombination take refuge in the telomeres.

PMID- 21887881
TI  - Conversation with Dr. G. K. Rath. [Interviewed by Sapna Gupta].

PMID- 21887882
TI  - Conversation with Dr. K. A. Dinshaw. [Interviewed by Meena Tiwari].

PMID- 21887883
TI  - FPIN's clinical inquiries: antibiotic prophylaxis to prevent recurrent UTI in
      children.

PMID- 21887884
TI  - Global Programme to eliminate lymphatic filariasis: progress report on mass drug
      administration, 2010.

PMID- 21887885
TI  - Leprosy update, 2011.

PMID- 21887886
TI  - Corporate colleagues: shared goals, shared value.

PMID- 21887887
TI  - Health educators and foundations release competencies and action strategies for
      interprofessional education.

PMID- 21887888
TI  - Stroop interference, hemodynamic response and aging: an event-related fMRI study.
AB  - In a Stroop interference task, subjects are required to name the color of a word,
      while ignoring the meaning of the word. The increase in time taken to name the
      color name if the underlying word is incongruent to the color is called Stroop
      color-word interference effect. With increasing age, reaction time (RT) is
      slowed. In an functional magnetic resonance imaging (fMRI) study we investigated
      the effects of aging (subjects from 22 to 75 years of age) on the performance in
      the color-word matching Stroop task and on the hemodynamic response. The present
      study shows that middle-aged adults were generally slowed but no increased
      interference effect occurred. Further, middle-aged adults showed increased
      activations in several task-related regions, mainly in the inferior frontal
      junction (IFJ) area (bilaterally) and the presupplementary motor area. For the
      middle-aged subjects, regions in the inferior frontal gyrus (IFG), the basal
      putamen and the occipital lobe were additionally recruited, indicating a stronger
      dependence on compensatory strategies. Further, middle-aged subjects showed
      generally a greater magnitude of the hemodynamic response, resulting in greater
      percent signal changes.

PMID- 21887890
TI  - Radiation risks of diagnostic imaging.

PMID- 21887889
TI  - Interleukin-10 protects against inflammation-mediated degeneration of
      dopaminergic neurons in substantia nigra.
AB  - Inflammation has been increasingly recognized to play an important role in the
      pathogenesis of Parkinson's disease (PD). Using immunocytochemistry and electron
      microscopy, we found that intranigral injection of lipopolysaccharide (LPS)
      caused marked microglial activation and a dose-dependent selective loss of
      dopaminergic neurons, which was mediated by apoptosis as evidenced by prominent
      TUNEL labeling. RNase protection assays revealed that mRNA for Bax, Fas and the
      pro-inflammatory cytokines interleukin (IL)-1alpha, IL-1beta, IL-6 and tumor
      necrosis factor (TNF)-alpha were significant increased ipsilaterally in LPS
      injected side of SN, while expression of the anti-apoptotic gene Bcl-2 was
      decreased. Osmotic pump infusion of IL-10, a global inhibitor of cytokine
      synthesis, protected against LPS-induced cell death of dopaminergic neurons, with
      a corresponding decrease in the number of activated microglia, suggesting that
      the reduction in microglia-mediated release of inflammatory mediators may
      contribute to the anti-inflammatory effect of IL-10. Our results provide evidence
      that LPS induces apoptotic cell death in SNpc, which is likely through the
      expression of Fas, Bax, caspase-3, and the pro-inflammatory cytokines.

PMID- 21887891
TI  - The pH ruler: a Java applet for developing interactive exercises on acids and
      bases.
AB  - In introductory biochemistry courses, it is often a struggle to teach the basic
      concepts of acid-base chemistry in a manner that is relevant to biological
      systems. To help students gain a more intuitive and visual understanding of
      abstract acid-base concepts, a simple graphical construct called the pH ruler
      Java applet was developed. The applet allows students to visualize the abundance
      of different protonation states of diprotic and triprotic amino acids at
      different pH values. Using the applet, the student can drag a widget on a slider
      bar to change the pH and observe in real time changes in the abundance of
      different ionization states of this amino acid. This tool provides a means for
      developing more complex inquiry-based, active-learning exercises to teach more
      advanced topics of biochemistry, such as protein purification, protein structure
      and enzyme mechanism.

PMID- 21887892
TI  - When unemployed means uninsured: the toll of job loss on health coverage, and how
      the Affordable Care Act will help.
AB  - Chronically high unemployment has left millions of Americans without health
      insurance, which disappeared along with their wages and other job benefits.
      Although continuing health coverage through COBRA is an option for some workers,
      the often prohibitively high cost means that relatively few elect to purchase it.
      When fully implemented in 2014, the Affordable Care Act will dramatically
      increase health insurance options for people who lose their jobs. Even so, gaps
      in coverage will remain a risk for many workers who become unemployed or are
      transitioning to a new job. To help bridge coverage gaps until 2014, policymakers
      should consider reestablishing the COBRA premium subsidies that helped millions
      of people who lost their jobs in 2008-2010.

PMID- 21887893
TI  - Safeguard or mollycoddle? Medical student placements in Aboriginal communities.
      Comment.

PMID- 21887894
TI  - [Pohoda no. I (death on music festival)].
AB  - A fatal accident of a young man, visitor of the summer music festival, shocked
      the whole Slovak society. Many unanswered questions concerned a causality of the
      incident arose immediately. Altough most questions have been focused to technical
      experts concerning the cause of a tent fall, the forensic medicine can bring some
      important reflections and conclusions, too. An absence of natural defense
      mechanisms of the accident's victim should be explained only through malignant
      affection of the body reflectoris reactions by exogenous substance, which might
      depress natural senzoric or motoric response while being in acute danger from
      falling tent's construction.

PMID- 21887895
TI  - [Pohoda no. II (delayed death--following music festival)].
AB  - A mass tragedy on the Slovak biggest music festival "POHODA", caused by a
      windstorm, shocked whole society, even abroad. Many questions concerned a
      causality and a circumstances of the incident arose immediately. The forensic
      autopsies of victims (29-aged man and 19-aged woman) represented a very special
      expertise act in police investigation of the case.

PMID- 21887896
TI  - [Effect of windshield washer fluid on breathalyser results].
AB  - In this test were verify the possibility of the influence of windshield washer
      fluid containing ethanol on an alcohol breath test. The premise was that anti
      freeze washer fluids used in automobiles contain ethanol, and that the use of
      such fluids results in ethanol vapour permeating the automobile's cabin. Tests
      were carried out on individuals seated on the front seats of an enclosed
      automobile cabin. Five different types of anti-freeze washer fluids suited for
      temperatures between -19 degrees C to -35 degrees C commonly available at a range
      of different petrol station chains throughout the Czech Republic were used. In
      total 34 measurements were taken. Not even in one instance could a measurement of
      zero be obtained within 60 seconds to 4 minutes of the use of ethanol-based
      washer fluid. The longest positive test lasted for 13 minutes. The highest
      measured value was 0.71% per hundred. Immediately after exiting the automobile
      and taking several breaths of fresh outside air tests were negative in all cases.
      All tests subjects described a clear odour of windscreen washer fluid in the
      cabin in all instances, which was evident even after breathalyzer tests showed
      zero values. It is hence verified that using ethanol-based windscreen washer
      fluid which is commonly accessible on our market to spray the windscreen can skew
      the results of breathalyzer tests in the sense of generating false positives. Due
      to the characteristic odour described, drivers should themselves be aware that
      any test undertaken could not be in his or her favour. To eliminate the apparent
      presence of alcohol, it is however enough to exit the cabin and to take several
      (2-3) breaths of fresh air to absolutely guarantee a fair test. A positive test
      at this stage points to a different underlying reason than ethanol-based
      windscreen washer fluid being used.

PMID- 21887897
TI  - An autopsy case of multiple psychotropic drug poisoning.
AB  - A fatal poisoning case involving etizolam, phenobarbital, promethazine and
      chlorpromazine is presented. Quantitative toxicological analysis showed that the
      concentrations of etizolam, phenobarbital, promethazine and chlorpromazine in the
      femoral blood were 86 ng/ml, 5082 microg/ml, 0.107 microg/ml and 0.144 microg/ml,
      respectively, and large amounts of drugs were also detected in the stomach
      contents. We conclude that the cause of death was due to the interaction of
      multiple psychotropic drugs.

PMID- 21887898
TI  - [Usage of automatic voice transcription in autopsy service].
AB  - The paper describes the computer program NEWTON Dictate which is used for speech
      recognition and transcription. The possible uses of this program in forensic
      medicine are discussed, especially concerning the recognition and transcription
      of the autopsy findings. Specific conditions of the forensic medicine are
      introduced, with their influence on speech recognition and translation being the
      focus. The authors analyze program improvement aimed at reducing mistakes in
      recognition and transcription which may occur during autopsy work flow. Such
      improvement involves appropriate vocabulary usage and special vocal adaptation.
      The role of the autopsy secretary is acknowledged.

PMID- 21887899
TI  - A fatal case of severe methemoglobinemia presumably due to chlorate ingestion.
AB  - A fatal case due to severe methemoglobinemia is presented. A male in his forties
      was found unconscious in his house and, despite intensive care, death was
      confirmed approximately 11 hours later. Toxicological analysis using ion
      chromatography revealed the presence of chlorate in the stomach contents.
      However, chlorate was not detected in the blood, and no other drugs or ethanol
      were detected in the blood either. We concluded that the cause of death was
      presumably due to chlorate poisoning, based on the results of the autopsy and the
      toxicological examination.

PMID- 21887900
TI  - [Analysis of the sudden heart death causes in selected sample of dead].
AB  - Sudden cardiac death (SCD) is death from cardiac causes within one hour of the
      onset of symptoms. In the Czech Republic, there is no SCD registry, analyses of
      SCD causes are rare and there is no functional connection between the results of
      an autopsy on a person with SCD and examination of relatives who are at risk of a
      similar disease. The authors reviewed available autopsy records of the Department
      of Forensic Medicine and Medical Law of the University Hospital Olomouc over a
      specified period of time to find persons with severe coronary artery disease,
      heart failure or deaths from unknown causes in a specific age range.
      Subsequently, the available information about the circumstances of SCD was
      analyzed.

PMID- 21887901
TI  - Bisphosphonate associated osteonecrosis of the jaw; similarities and differences
      in oncologic and non-oncologic patients.

PMID- 21887902
TI  - Insulin resistance is associated with increased cardiovascular risk in Asian
      Indians with normal glucose tolerance--the Chennai Urban Rural Epidemiology Study
      (CURES-66).
AB  - OBJECTIVE: The aim of the study was to assess the association of Insulin
      Resistance [IR] assessed by Homeostasis Assessment model (HOMA-IR) with
      cardiovascular risk factors in subjects with Normal Glucose Tolerance [NGT] in
      Asian Indians. METHODS: This cross-sectional study recruited subjects from the
      Chennai Urban Rural Epidemiology Study [CURES] an epidemiological study in a
      representative population of Chennai [formerly Madras], in South India. We
      included 1550 subjects with normal glucose tolerance, ie, fasting plasma glucose
      < 100 mg/dl [5.6 mmol/L] and 2 hour post load plasma glucose < 140 mg/dl [7.8
      mmol/L]. IR was calculated using the homeostasis assessment model (HOMA-IR) using
      the formula: fasting insulin (1IU/mL) fasting glucose (mmol/L)/22.5. Metabolic
      syndrome [MS] was defined based on modified Adult Treatment Panel III (ATP III)
      guidelines. RESULTS: HOMA-IR was found to be significantly associated with
      systolic blood pressure (beta = 0.100, p < 0.001), diastolic pressure (beta =
      0.094, p < 0.001), total cholesterol (beta = 0.068, p = 0.005), serum
      triglycerides (beta = 0.105, p < 0.001), LDL cholesterol (beta = 0.118, p <
      0.005), and HDL cholesterol (beta = -0.060, p < 0.001) even after adjusting age,
      gender and BMI. Subjects with family history of type 2 diabetes had significantly
      higher HOMA-IR [p = 0.011] compared to those without family history. In relation
      to physical activity, subjects with heavy grade activity had significantly lower
      HOMA-IR values compared to the light grade activity [p < 0.001] Subjects with
      generalized obesity [p < 0.001] and abdominal obesity [p < 0.001] had
      significantly higher HOMA-IR which remained statistically significant even after
      adjusting for age and gender. There was a linear increase in the mean values of
      HOMA IR with increase in number of components of MS [p for trend < 0.001]
      CONCLUSION: Among Asian Indians who are known to have high risk of premature
      coronary artery disease and diabetes, a significant association exists between
      insulin resistance with cardiovascular risk factors even among NGT subjects.

PMID- 21887903
TI  - Maternal obesity and pregnancy outcome: a prospective analysis.
AB  - OBJECTIVE: To analyze whether the obese women have an increased risk of pregnancy
      complications and adverse fetal outcome. METHODS: The longitudinal prospective
      study was carried out in the Obst and Gynae department, IPGME and R, Kolkata. The
      study enrolled 422 pre-pregnant obese women with pregnancy as study population
      and equal number of non obese pregnant mothers as controls. Body mass index (BMI)
      was > or = 30.0 kg/m2 and 20-22 kg/m2 in obese and control group respectively.
      RESULTS: In comparison to average weight pregnant women, obese pregnant women
      were at increased risk of gestational diabetes mellitus (19.43 vs 3.79%; p <
      0.001), pregnancy induced hypertension (12.32 vs 2.36%; p < 0.001), pre-eclampsia
      (8.76 vs 3.31%; p < 0.001), preterm labor in less than 34 week gestation (7.58 vs
      3.55%; p < 0.001), cesarean section (36.72 vs 17.53%; p < 0.001), instrumental
      deliveries (12.32 vs 5.21%; p < 0.001) and postpartum infection morbidities (9.95
      vs 3.79%; p < 0.001). These women were more prone to develop overt diabetes
      (2.36% vs 0) and chronic hypertension (5.21 vs .47% ) in future as well. Neonates
      of obese women were mostly large for gestational age, macrosomic and they had
      high incidences of birth injuries, shoulder dystocia, premature deliveries, late
      fetal deaths and congenital malformations particularly spina bifida, cleft lip,
      cleft palate and heart defect. CONCLUSION: As obesity is considered to be a
      modifiable risk factor, preconception counseling and creating awareness regarding
      health risks associated with over weight and obesity should be encouraged.

PMID- 21887904
TI  - CYP2C19 polymorphism as a predictor of personalized therapy in South Indian
      population.
AB  - OBJECTIVES: To study allelic variants of CYP2C19 gene in South Indians. METHODS:
      A total of 220 individuals (167 Males and 53 Females) confirmed to be healthy on
      the basis of their physical examination and laboratory studies were recruited in
      the study. Genotyping of CYP2C19*2 and *3 polymorphisms was performed by a
      Polymerase chain reaction-Restriction fragment length polymorphism method.
      RESULTS: The genotypic results of both CYP2C19*2 and CYP2C19*3 are considered to
      establish the frequency of poor metabolisers related to monooxygenase mediated
      drug metabolism. Individuals who were homozygous mutants for both m1 (m1/m1) and
      m2 (m2/m2) and heterozygous for both m1 and m2 (ml/m2) mutations were categorized
      as poor metabolisers. In the present study the frequency of Homozygous Extensive
      Metabolizers (HomoEM), Heterozygous Extensive Metabolizers (HetEM) and Poor
      Metabolizers (PM) are 32.2% (n = 71), 52.8% (n = 116) and 15.0% (n = 33)
      respectively. CONCLUSION: Since inter individual genetic variations play crucial
      role in variety of drugs, the identification of intermediate and poor drug
      metabolizers based on CYP2C19 polymorphism can be a basis for the standardization
      of personalized therapy.

PMID- 21887905
TI  - Sublingual piroxicam in migraine without aura.
AB  - OBJECTIVE: The aim of the present study was to compare the analgesic efficacy of
      a single dose of sublingual piroxicam to that of a placebo during acute attacks
      of migraine without aura. METHODS: The drug (N = 30) or a placebo (N = 30) was
      administered, on randomisation and double-blind basis, to 60 patients between 18
      and 50 years of age suffering from migraine without aura. The patients were
      instructed to take a single tablet sublingually [corresponding to piroxicam 40 mg
      or placebo] and the severity of the painful symptomatology and associated
      symptoms were evaluated by this study. RESULTS: The patients treated with
      sublingual piroxicam showed a significant (P < 0.05) decrease in pain intensity
      15 minutes after ingestion; they went on to show a further reduction in the 24
      hours after drug administration. On the contrary, the group treated with placebo
      showed a significant reduction of symptoms only after seven hours of observation.
      Associated symptoms disappeared significantly (P < 0.05) after sublingual
      piroxicam administration. In 83.3%, the drug resulted in excellent to good
      response as compared to only 10% in the placebo group. No local and systemic side
      effects were reported with sublingual piroxicam. CONCLUSIONS: The present study
      has demonstrated that for the acute management of migraine without aura
      sublingual piroxicam showed significant analgesic effect with excellent
      tolerability.

PMID- 21887906
TI  - Retrospective analysis of necropsy findings in patients of H1N1 and their
      correlation to clinical features.
AB  - India reported its first case of H1N1 in July 2009 in Pune and since then, the
      number of reported cases and deaths exploded in India. Since very little data is
      available about histopathological findings in patients of H1N1 fatal cases in
      India, a retrospective chart analysis of necropsy findings of 15 cases of 2009
      H1N1 fatal cases was performed. Common clinical features were fever, cough, and
      breathlessness followed by sore throat and rhinorrhea. Common lung findings were
      mononuclear cell infiltration, thick alveolar septae, intraalveolar hemorrhage.
      The other findings were congested pulmonary blood vessels, pulmonary edema,
      cytomegaly, fibrin accumulation and formation of eosinophilic membrane. These
      findings are suggestive of diffuse alveolar damage (DAD) and DAD with hemorrhage.
      All patients who underwent necropsy had radiographic findings suggestive of
      unilobar or multilobar pneumonia. This clinical finding can be correlated
      pathologically in these patients as all of them had either polymorphonuclear or
      mononuclear infiltrate. Furthermore, necrotizing pneumonitis pattern seen on
      these patients is the likely cause of mortality in these patients. Although
      clinical ARDS pattern was noted in all these patients, it was well correlated in
      lung pathology in all these cases.

PMID- 21887907
TI  - Study of patient characteristics/profile and factors determining the (immediate)
      outcome in spontaneous subarachnoid hemorrhage.
AB  - AIMS AND OBJECTIVES: The aims of the study were to delineate the risk factors,
      type and location of underlying pathology, outcome and the determinants of
      outcome in patients with spontaneous subarachnoid hemorrhage. MATERIAL AND
      METHODS: Forty consecutive patients with spontaneous subarachnoid hemorrhage on
      neuroimaging scan were recruited over a period of 1 year. Risk factors profile,
      site and type of pathology seen on angiography were assessed in all patients.
      Patient outcome at the end of hospital stay was assessed using the Glasgow
      Outcome Scale (GOS) and was analysed with respect to demographic factors,
      premorbid risk factors, initial WFNS scoring, neuroimaging findings and
      complications during in-hospital stay. RESULTS: Of the total 40 patients in the
      study, 43% were males and 57% were females. The mean age in study group was 49.63
      yrs (SD 13.12). Fifty percent patients were hypertensive, 22.5% were smokers and
      alcohol intake was reported by 17.5%. Saccular aneurysms were seen in 80%
      patients and arteriovenous malformations in 7.5%. Aneurysms were more common in
      the anterior circulation than in the posterior circulation. Poor outcome was
      associated with higher age, hyponatremia, higher World Federation of
      Neurosurgeons (WFNS) grade on admission, presence of vasospasm on angiography,
      fever any time during the course in hospital and requirement of ventilatory
      support. CONCLUSION: Gender, site of aneurysmal bleeding (anterior/posterior
      circulation) and procedure performed (coiling/clipping) do not influence the
      immediate outcome of patients with subarachnoid hemorrhage. Further studies on
      Indian subset of patients are necessary to determine the patient characteristics
      and factors influencing the long-term outcome in spontaneous subarachnoid
      hemorrhage.

PMID- 21887908
TI  - Organ donation: victory after death.
AB  - Despite the Transplantation of Human Organ Act passed in Indian Parliament in
      1994, cadaver liver and/or kidney transplant are infrequently performed (in a few
      private hospitals) in our country compared to living donor liver or kidney
      transplant. The need for performing more cadaver liver and/or kidney transplants
      in private and public hospitals is obvious. Immediate measures which should be
      taken to facilitate more cadaver organ transplant both in private and public
      hospitals are suggested. Organ donation is for an individual or a family an
      invaluable opportunity, to register victory after death.

PMID- 21887909
TI  - LA ball thrombus and peripheral embolisation.

PMID- 21887910
TI  - Striae--an unusual cause.

PMID- 21887911
TI  - Bisphosphonate-induced osteonecrosis of the jaw.
AB  - Bisphosphonates are routinely used in the prevention and treatment of
      osteoporosis. Osteonecrosis of the jaw is known to be an important but rare
      complication of bisphosphonate usage. We present our experience with two patients
      of osteonecrosis of the jaw due to bisphosphonate usage.

PMID- 21887912
TI  - Lymphoplasmacytic lymphoma and IgA nephropathy in a patient with hepatitis C
      infection.
AB  - Hepatitis C virus (HCV) infection is known to be associated with
      lymphoplasmacytic lymphoma. Reports are available of IgA nephropathy along with
      HCV infection. We are reporting the case of a 44 years old male who was diagnosed
      to have Hepatitis C infection with lymphoplasmacytic lymphoma and IgA
      nephropathy.

PMID- 21887913
TI  - Acute myocardial injury and rhabdomyolysis caused by multiple bee stings.
AB  - Massive envenomation by honey bees is capable of causing multiorgan dysfunction
      as a result of direct toxic effect of massive envenomation and secondary to
      systemic anaphylactic reactions. Acute myocardial ischemia due to bee
      envenomation is a rare event. We report the case of a 65 year old lady who
      presented with acute myocardial ischemia, severe rhabdomyolysis and angioedema
      following massive bee envenomation.

PMID- 21887914
TI  - Lupus nephritis associated with CD20+ B-cell NHL.
AB  - The combination of NHL and documented malignancy-associated glomerulonephritis is
      uncommon. Also, no single renal pathological entity is consistently found in
      patients with NHL. Epstein-Barr virus (EBV) infection may manifest as systemic
      lupus erythematosus (SLE) and/or diffuse large cell lymphoma (DLBCL) in a
      genetically/ immunologically susceptible individual with defective cytotoxic T
      cell response against EBV. We describe lupus nephritis in a 45 years old male
      suffering from untreated NHL. CD20+ DLBCL was demonstrated by
      immunohistochemistry of the neck lymph node (LN) biopsy performed for generalized
      lymphadenopathy. Renal biopsy revealed class V + IV lupus nephritis. Serology
      demonstrated EBV infection. Complete clinical remission of both SLE and DLBCL was
      achieved post-therapy with six-cycle rituximab, cyclophosphamide, vincristin,
      adriablastin, methylprednisolone (R-CHOP) regime. This case report demonstrated
      the complex relationships between NHL, SLE, EBV and membranous
      glomerulonephritis. The presented case is remarkable not only because of the rare
      association of SLE and DLBCL, but also because of its successful treatment with R
      CHOP.

PMID- 21887915
TI  - Tubercular liver abscess in immuno-competent patients.
AB  - We report two cases, the first one a 35 years old male, chronic alcoholic, and
      the other, a 15 years old boy, who presented to us with fever, Rt. hypochondrial
      pain, with USG-Abdomen revealing multiple liver abscesses in the first, and a
      single large abscess in the second. Both patients showed leucocytosis and, mildly
      deranged Liver Function Tests. Aspirated pus was sterile, and the patients did
      not show any clinical improvement despite broad spectrum antibiotics and
      amoebicides. Re-aspiration of pus after two weeks revealed the presence of
      Mycobacterium tuberculosis and both patients showed a dramatic improvement
      clinically after starting Anti-tubercular treatment. These cases are being
      reported because of the rarity of tubercular liver abscesses, and the importance
      of suspecting mycobacterial infection in patients of liver abscess not responding
      to conventional treatment.

PMID- 21887916
TI  - Acute mixed cellular and humoral rejection of renal allograft with leucopenia.
AB  - Diagnosis and management of acute renal allograft dysfunction often pose
      challenge to nephrologists during practice. Acute rejection is a major cause of
      acute graft dysfunction but is rare in patients with leucopenia. Acute rejection
      can have either humoral or cellular components or sometimes mixed components.
      Mixed acute cellular and humoral rejection often present as steroid resistant
      rejection. Here we report a patient with live related renal transplant recipient
      with acute graft dysfunction with leucopenia who was found to have mixed acute
      cellular and humoral rejection.

PMID- 21887917
TI  - Isolated lingual dystonia : responding to anticholinergic treatment.
AB  - We report a 42 year-old woman with 6 month history of isolated lingual dystonia
      induced during speaking and was treated with anticholinergic drug. She
      experienced a marked improvement in her abnormal tongue movements. Primary
      lingual dystonia is a rare presentation.

PMID- 21887918
TI  - Medical philately. Discovery of immunoglobulins (antibodies).

PMID- 21887919
TI  - Anthropometric changes in patients receiving highly active antiretroviral therapy
      (ART).

PMID- 21887920
TI  - [Advances in hematopathology].

PMID- 21887921
TI  - [Good ideas like good wine need time to mature].

PMID- 21887922
TI  - [Diagnostics in hematopathology. Preface].

PMID- 21887923
TI  - [Histological diagnosis of Ph-negative myeloproliferative neoplasia. An
      overview].
AB  - A histological picture in pretreatment bone marrow trephine biopsy is an
      essential part of Ph-negative myeloproliferative neoplasm diagnosis according to
      WHO classification. Polycythaemia vera is histologically defined as a
      hypercellular trilinear myeloproliferation. Hypercellular haematopoiesis with
      granulocytic and megakaryocytic proliferation is typical for primary
      myelofibrosis. In essential thrombocythaemia the haematopoiesis is normocellular
      with proliferation of megakaryocytes only. The most important differential
      diagnostic features are morphology and distribution of megakaryocytes, and
      presence of fibrosis. In primary myelofibrosis there are typically ,dysplastic"
      megakaryocytes forming tight (dense) clusters, and variable extent of fibrosis,
      while mature megakaryocytes forming loose clusters and no fibrosis are found in
      essential thrombocythaemia. In reactive thrombocytosis and erythrocytosis the
      number of normally appearing megakaryocytes is not increased and they are not
      forming clusters. Prodromal (latent) phases of myeloproliferative neoplasms often
      unrecognized by recent WHO classification criteria are discussed as well as a
      differential diagnosis of myeloproliferative disorders associated with
      thrombocytosis.

PMID- 21887924
TI  - [Malignant lymphomas, or what do clinicians expect from pathologists?].
AB  - Although the diagnosis and treatment of malignant lymphomas achieved considerable
      progress, their expansion was more or less independent. Therefore, for quick,
      fast and clinical relevant diagnostic process is necessary that clinical
      physicians and pathologists work closely together. Clinicians have to give
      pathologists key informations, but pathologists have to be ready to ask for them
      when needed. This article gives some examples which illustrate these principles.

PMID- 21887925
TI  - [Importance of cyclin D1 (and CD5) detection in the diagnosis of malignant
      lymphomas other than mantle cell lymphoma].
AB  - In association to our undestanding of the pathogenesis and biopsy diagnosis of
      mantle cell lymphoma using immunohistochemical detection of cyclin D1 expression
      and/or FISH detection of t(11;14)(q13;q32) all the lymphomas interfering with
      these factors are discussed in a form of a review. This includes a cyclin D1
      negative mantle cell lymphoma, as well as other than MCL lymphomas showing
      positive intranuclear cyclin D1 positivity due to the changes either at
      transcriptional or postranscriptional levels. In addition to the MCL, the cyclin
      D1 positivity might be detected in the cells of hairy cell leukemia, plasmocytic
      lymphoma and diffuse large B-cell lymphoma. In the first two lymphomas the
      differential diagnostic problems usually do not arise (with exception of G3
      plasmacytoma) and cyclin D1 expression might be of interess to understand better
      their biology, or to represent a prognostically significant factor. In contrast,
      cyclin D1 positivity in diffuse large B-cell lymphomas demonstrates the possible
      role of cyclins in the pathogenesis of this lymphoma and may lead to the problems
      of the differential diagnosis of aggressive variant of pleomorphic MCL
      (especially when occuring with CD5 positivity coexpression ). The review includes
      discussion related to the significance of cyclin D1 positivity and to the
      approach in the immunohistochemical and FISH analysis of the biopsy material.

PMID- 21887926
TI  - Quantitative molecular analysis in mantle cell lymphoma.
AB  - A molecular analysis has three major roles in modern oncopathology--as an aid in
      the differential diagnosis, in molecular monitoring of diseases, and in
      estimation of the potential prognosis. In this report we review the application
      of the molecular analysis in a group of patients with mantle cell lymphoma (MCL).
      We demonstrate that detection of the cyclin D1 mRNA level is a molecular marker
      in 98% of patients with MCL. Cyclin D1 quantitative monitoring is specific and
      sensitive for the differential diagnosis and for the molecular monitoring of the
      disease in the bone marrow. Moreover, the dynamics of cyclin D1 in bone marrow
      reflects the disease development and it predicts the clinical course. We employed
      the molecular analysis for a precise quantitative detection of proliferation
      markers, Ki-67, topoisomerase IIalpha, and TPX2, that are described as effective
      prognostic factors. Using the molecular approach it is possible to measure the
      proliferation rate in a reproducible, standard way which is an essential
      prerequisite for using the proliferation activity as a routine clinical tool.
      Comparing with immunophenotyping we may conclude that the quantitative PCR-based
      analysis is a useful, reliable, rapid, reproducible, sensitive and specific
      method broadening our diagnostic tools in hematopathology. In comparison to
      interphase FISH in paraffin sections quantitative PCR is less technically
      demanding and less time-consuming and furthermore it is more sensitive in
      detecting small changes in the mRNA level. Moreover, quantitative PCR is the only
      technology which provides precise and reproducible quantitative information about
      the expression level. Therefore it may be used to demonstrate the decrease or
      increase of a tumor-specific marker in bone marrow in comparison with a
      previously aspirated specimen. Thus, it has a powerful potential to monitor the
      course of the disease in correlation with clinical data.

PMID- 21887927
TI  - Burkitt lymphoma (BL): reclassification of 39 lymphomas diagnosed as BL or
      Burkitt-like lymphoma in the past based on immunohistochemistry and fluorescence
      in situ hybridization.
AB  - Burkitt lymphoma (BL) is a well characterized entity. For atypical findings a
      term Burkitt-like lymphoma (B-LL) was applied in the past, but the interpretation
      of the morphological appearances was subjective and poorly reproducible. We used
      a combined approach (morphology using classical histological staining;
      immunohistochemistry-IHC; fluorescence in situ hybridization-FISH on interphase
      nuclei; cytogenetics) to perform a retrospective study on 39 patients diagnosed
      as BL and B-LL at our department in the years 1982 to 2002. By FISH we
      demonstrated t(8;14)(q24;q32) in 31 patients; in further two we found a break at
      8q24, suggestive of a variant translocation. In three patients with the
      cytogenetic investigation available we confirmed the findings of FISH--two
      lymphomas had the t(8;14)(q24;q32), one had t(2;8)(p12;q24). IHC showed CD20,
      CD10, BCL-6, p53 expression, and Ki-67 antigen in > 95% of the tumor cell
      population in a majority of the patients. There was a group of 4 patients in whom
      the t(8;14)(q24;q32) or a break at 8q24 were not found (FISH). These cases were
      reclassified within the WHO defined grey zone subgroup of B-cell lymphoma
      unclassifiable with features intermediate between diffuse large cell lymphoma
      (DLBCL) and Burkitt lymphoma--I-DLBCL/BL. Two further cases were reclassified as
      DLBCL based on a combined IHC and FISH findings. A lymphoma of one of these
      patients had breaks at 3q27 (BCL6) and at 14q32 (IGH) suggestive of
      t(3;14)(q27;q32). The overall survival estimate of 33 patients with the diagnosis
      of BL was 54%. Most of deaths occurred within 6 months after the tumor diagnosis.
      The unfavorable clinical outcome appears to be associated with a strong
      expression of the p53 protein in the tumor cell population. Individually utilized
      methods in the diagnosis of BL may lead to false diagnostic conclusions. A
      combined approach helps to establish a more reliable diagnosis of BL and to
      separate grey zone lymphomas I-DLBCL/BL and DLBCL with morphological mimics of BL
      to start adequate treatment. I-DLBCL/BL is a non-homogenous group of lymphomas
      necessitating further analysis in a prospective study.

PMID- 21887928
TI  - [Our experience with detection of JAK2 mutations in paraffin-embedded trephine
      bone marrow biopsies of patients with chronic myeloproliferative disorders].
AB  - Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis
      (PMF) are Philadelphia chromosome-negative myeloproliferative neoplasms (MPN)
      characterized by JAK2 mutation. The exon 14 V617F mutation is present in almost
      all patients with PV and in approx. 60% of patients with ET and PMF. The
      importance of JAK2V617F in the differential diagnostic considerations is still
      unclear and here the BM morphology examination still represents an important
      diagnostic tool. In the WHO classification of Ph1-negative MPNs, the
      identification of JAK2 mutations represents a major diagnostic criterion of these
      diseases. Therefore we decided to implement the examination of JAK2V617F mutation
      in formalin-fixed paraffin-embedded biopsy specimens of patients with Ph1
      negative MPN using allele-specific PCR. In addition, in all JAK2 V617F negative
      patients with PV we sequenced the whole JAK2 exon 12. Until now we examined up to
      200 patients with clinically confirmed MPN and our results in all three
      categories PV, ET and PMF are in agreement with earlier published data. Paraffin
      embedded tissues represent a valuable source of DNA which can be used in the
      diagnostics of both JAK2 exon 12 and exon 14 mutations. It is of particular
      importance if the fresh material is not available and there is a clinical and/or
      research utility for the performance of PCR on archival bone marrow samples with
      PV, ET or PMF suspicion.

PMID- 21887929
TI  - Coincidence of chronic lymphocytic leukaemia with Merkel cell carcinoma: deletion
      of the RB1 gene in both tumors.
AB  - The authors report a case of a 64-year-old man with chronic lymphocytic leukaemia
      (CLL) diagnosed 5 years ago. Recently, the patient was admitted with a tumour of
      the skin in the left lumbar region. Histological and immunohistochemical
      examinations established the diagnosis of Merkel cell carcinoma (MCC). Electron
      microscopic examination revealed the formation of spherical aggregates of
      intermediate-sized filaments in the perinuclear region. The coincidence of MCC
      and CLl is rather rare and in published cases, no cytogenetic examinations were
      performed. We examined the RB1 gene using the interphase FISH method. A biallelic
      deletion in CLL tumour cells was detected; in MCC tumour cells, biallelic
      deletion was found in 33% of the cells and monoallelic deletion in 57% of the
      cells. In addition, chromosome 6 trisomy and 1p36 deletion were detected.
      Examination of non-neoplastic cells of the patient's skin showed a biallelic
      presence of the RB1 gene. According to the relevant literature, examination of
      the RB1 gene in CLL has informational value as a prognostic factor. The
      relationship between deletion of the RB1 gene and prognosis in MCC has not yet
      been determined and needs more research.

PMID- 21887930
TI  - [What is your diagnosis? 1. Lymphadenopathy in sarcoidosis. 2. Toxoplasmic
      lymphadenitis (Piringer-Kuchinkov). 3. Reactive (paraneoplastic) granulomatous
      lymphadenopathy. 4. Granulomatous cat-scratch lymphadenitis].

PMID- 21887931
TI  - Uterine leiomyoma with amianthoid-like fibers.
AB  - A rare case of a gynecologic type leiomyoma with amianthoid-like fibers is
      presented. The 6 cm tumor was found in the uterus of a 46-year-old woman.
      Histologically, it contained a cellular spindle cell population with numerous
      eosinophilic amianthoid-like fibers. The morphology closely resembled that of
      palisaded "amianthoid" myofibroblastoma. Immunohistochemically, the lesion showed
      a smooth muscle phenotype with expression of h-caldesmon, desmin, alpha smooth
      muscle actin, and with negativity for CD10 and the S100 protein. The finding of
      amianthoid-like fibers expands the morphologic spectrum of leiomyomas. It
      represents one of the overlapping features between leiomyoma and palisaded
      myofibroblastoma.

PMID- 21887932
TI  - Glomus tumor of the stomach: a case report and review of the literature.
AB  - Glomus tumor is a benign soft tissue neoplasm which commonly affects the
      subungual region of the fingers. But the tumors can also arise in the other sites
      such as the antrum of the stomach. We are reporting a case of a glomus tumor of
      the stomach in a 71-year-old female patient who presented with dyspepsia. The
      tumor was confined to the lamina muscularis propria, it consisted of round cells
      with small uniform nuclei, which surrounded thin walled blood vessels.
      Immunohistochemistry revealed the tumor to be positive for smooth muscle actin,
      vimentin, calponin, h-caldesmon and negative for c-KIT, S-100, CD34, CD99,
      synaptophysin, chromogranin, desmin and EMA. The proliferation marker Ki-67 was
      positive in less than 5% of tumor cell nuclei. Glomus tumors are usually benign
      but malignant cases have been published. Criteria for the malignant potential of
      gastric glomus tumors remain poorly defined.

PMID- 21887933
TI  - Mucosal changes after a polyethylene glycol bowel preparation for colonoscopy are
      less than those after sodium phosphate.

PMID- 21887934
TI  - A perspective on organizational well-being.

PMID- 21887935
TI  - Demystifying and improving organizational culture in health-care.
AB  - Organizational culture is defined as the shared values and beliefs that guide
      behavior within each organization, and it matters because it is related to
      performance. While culture is generally considered important, it is mysterious
      and intangible to most leaders. The first step toward understanding
      organizational culture is to measure it properly. This chapter describes methods
      for measuring culture in health-care organizations and how these methods were
      implemented in a large academic medical center. Because of the consistent
      empirical link between the dimension of communication, other culture dimensions,
      and employee satisfaction, special attention is focused in this area.
      Specifically, a case study of successful communication behaviors during a major
      "change management" initiative at a large academic medical center is described.
      In summary, the purpose of this chapter is to demystify the concept of culture
      and demonstrate how to improve it.

PMID- 21887936
TI  - The organization's mission statement: give up hope or resuscitate? A search for
      evidence-based recommendations.
AB  - The increasing complexity and dynamicity of their environment compels health-care
      managers to search relentlessly for effective management instruments. One
      strategic tool that both academics and practitioners have deemed critical to the
      success of any health-care organization is the development of a meaningful
      mission statement. However, despite the seemingly omnipresence of the concept,
      studies indicate that creating an effective mission statement seems to be
      extremely difficult, if not downright frustrating for a lot of health-care
      managers. This inability to create an effective mission statement roots for the
      greater part in the fact that the previous literature has provided little
      practical guidance on how health-care administrators should formulate and deploy
      mission statements. Given the increasing pressure on health-care organizations to
      develop an effective mission statement, this chapter (1) provides a detailed
      analysis of the mission statement concept based on a thorough literature analysis
      and (b) offers empirically based recommendations on how to successfully formulate
      and implement a mission statement within a health-care organization based on a
      systematic analysis of relevant empirical research. These analyses and the
      derived evidence-based recommendations will help health-care managers to revive
      their mission statement and make it more than a piece of paper.

PMID- 21887937
TI  - Enhancing the cultural competency of health-care organizations.
AB  - According to the Census, racial/ethnic minority populations are growing at such a
      fast rate that by 2050 more than 50% of the population will belong to a minority
      group (US Census, 2001). The increasing diversity of the U.S. population is one
      of the many changes that health-care delivery organizations need to proactively
      address in order to better serve their community and improve their performance.
      In this paper, we argue that cultural competency not only is important from a
      societal perspective, i.e., reducing health disparities, but can also be a
      strategy for health-care organizations to improve quality, lower cost, and
      attract customers. We provide detailed recommendations for health-care leaders
      and managers to adopt in order to successfully serve a diverse patient
      population.

PMID- 21887938
TI  - The role of mission, organizational culture, and cultural competency in
      furthering the development of health-care organizations: a commentary.

PMID- 21887939
TI  - Employee engagement: a prescription for organizational transformation.
AB  - Ivanitskaya, Glazer, and Erofeev (2009) suggest that "the most fundamental
      element of any organization that helps the organization to survive is the
      individual person" (p. 109). It is the motivation of human capital that makes a
      health-care organization come to life. Health-care is a unique industry; its
      accomplishments are directly dependent upon the competencies and technical skills
      of its employees. "When people in the workplace fulfill their organizational
      roles, then the organization thrives" (Ivanitskaya et al., 2009, p. 110). Health
      care systems will require organizations that thrive and exhibit characteristics
      of continuous growth, expressing excessive levels of energy and an immense
      capacity for flourishing. Anticipating the challenges of the next decade, health
      care organizations must achieve a higher degree of employee engagement to enhance
      organizational performance and profitability. The data analyzed for this chapter
      indicate that employees who are engaged are more enthusiastic and aspired to
      achieve both individual and organizational success. The chapter concludes by
      suggesting five operating practices to establish an employee engagement culture-
      defining the employee's role in fulfilling the organization's purpose, selecting
      employees with capability and passion, supporting and valuing the employee,
      creating sustainable reward systems, and developing feedback and reinforcement
      mechanisms.

PMID- 21887940
TI  - The relationship between the survey-guided assessment of culture within specific
      nursing work groups and readiness for change.
AB  - Change within health-care systems is constant as it relates to the external and
      internal demands that require continual adaptation by providers. This chapter
      provides a summary of the history and research contributions related to the study
      of culture and change through the lens of the nursing profession. The review
      focuses upon nursing research publications and the knowledge gained, ranging from
      the earliest to current studies. There has been a substantial increase in
      research interest regarding the relationship between nursing culture and ability
      to change; however, there is a considerable gap that remains in understanding
      subgroups such as individual nursing units or departments, consistent use of
      tools to measure culture, and interventions that have made a difference over
      time. From a practical perspective, this discussion provides insight into the
      importance of recognizing the importance of assessing culture and integrating
      cultural feedback into operational improvement plans.

PMID- 21887941
TI  - Achieving organizational change in health-care through people and culture: a
      commentary.

PMID- 21887942
TI  - The four C's of leadership development.
AB  - One of the top domestic issues of concern to Americans is access to high-quality
      and affordable health-care, and there is a growing concern about how institutions
      struggling to survive within this trillion-dollar industry will increase their
      effectiveness in the future. This chapter outlines a process of leadership
      development using an action learning approach in one Midwestern health-care
      system over a period of three years. The process addresses both the development
      of the individual leader as well as the collective leadership capacity in an
      effort to sustain organizational learning and effectiveness over time. A model is
      presented that covers four phases or Four C's of development, which includes
      movement from individual Competency development, to the development of social
      capital through the enhancement of Connections and Creation of shared
      understanding, ultimately expanding Capacity for change within the organization.
      We also address other factors that must be taken into consideration that will
      either enhance or impede the concentric movement such as culture, sponsor
      support, and alignment of systems and structures.

PMID- 21887943
TI  - Leadership and organization development in health-care: lessons from the
      Cleveland Clinic.
AB  - Leaders in health-care today are faced with a wide array of complex issues. This
      chapter describes an innovative physician leadership development program at the
      Cleveland Clinic intended to enhance the leadership capacities of individuals and
      the organization. Propositions regarding the program's impact on organizational
      innovation, organizational commitment, social capital, and the human element of
      physician practice are offered for future examination.

PMID- 21887944
TI  - The evolving leadership development agenda in health-care: a commentary.

PMID- 21887945
TI  - Addressing dysfunctional relations among healthcare teams: improving team
      cooperation through applied organizational theories.
AB  - Previous research has demonstrated that communication failure and interpersonal
      conflicts are significant impediments among health-care teams to assess complex
      information and engage in the meaningful collaboration necessary for optimizing
      patient care. Despite the prolific research on the role of effective teamwork in
      accomplishing complex tasks, such findings have been traditionally applied to
      business organizations and not medical contexts. This chapter, therefore, reviews
      and applies four theories from the fields of organizational behavior (OB) and
      organization development (OD) as potential means for improving team interaction
      in health-care contexts. This study is unique in its approach as it addresses the
      long-standing problems that exist in team communication and cooperation in health
      care teams by applying well-established theories from the organizational
      literature. The utilization and application of the theoretical constructs
      discussed in this work offer valuable means by which the efficacy of team work
      can be greatly improved in health-care organizations.

PMID- 21887946
TI  - Characteristics of positive working relationships between nursing and support
      service employees.
AB  - Developing greater synergies will become increasingly necessary as the pressure
      on the health-care industry continues to increase. This research looks at the
      required characteristics to create positive working relationships with clinical
      staff in a health-care organization from the perspective of nonclinical staff.
      Ten different U.S. hospitals participated in this qualitative study with over 200
      individual participants. A recipe for successful relationship building from a
      nonclinical perspective is included.

PMID- 21887947
TI  - The impact of supervisor-subordinate relationships on nurses' ability to solve
      workplace problems: implications for their commitment to the organization.
AB  - This chapter uses the structural and relational dimension of social capital
      theory (SCT) as a lens for examining the impact of the supervisor-subordinate
      relationship on nurses' perceptions of the usefulness of their workplace
      networks, sociability, and affective commitment. A survey was used to collect
      data from 1,064 Australian nurses. The findings suggest that nurses rely on very
      small workplace networks (typically only one other person) with which they have
      strong ties. Further, in over half of the cases, the supervisor (the Nurse Unit
      Manager (NUM)) holds the centric position. Moreover, for those nurses who did not
      include the NUM in their workplace network, their position appears even worse.
      For example, the usual reason given by nurses for not including the NUM was that
      the NUM was unavailable. This is a concern for health-care management because the
      past two decades have delivered many changes to the nursing profession, including
      a reduction in the number of nursing positions and subsequent higher workloads.
      The consequences suggest that without effective workplace networks, nurses are
      working under conditions where solving problems is more difficult.

PMID- 21887948
TI  - Systems approach to address incivility and disruptive behaviors in health-care
      organizations.
AB  - In response to the growing evidence that disruptive behaviors within health-care
      teams constitute a major threat to the quality of care, the Joint Commission on
      Accreditation of Healthcare Organization (JCAHO; Joint Commission Resources,
      2008) has a new leadership standard that addresses disruptive and inappropriate
      behaviors effective January 1, 2009. For professionals who work in human
      resources and organization development, these standards represent a clarion call
      to design and implement evidence-based interventions to create health-care
      communities of respectful engagement that have zero tolerance for disruptive,
      uncivil, and intimidating behaviors by any professional. In this chapter, we will
      build an evidence-based argument that sustainable change must include
      organizational, team, and individual strategies across all professionals in the
      organization. We will then describe an intervention model--Toxic Organization
      Change System--that has emerged from our own research on toxic behaviors in the
      workplace (Kusy & Holloway, 2009) and provide examples of specific strategies
      that we have used to prevent and ameliorate toxic cultures.

PMID- 21887949
TI  - Condition critical: intervening in health-care teams and working relationships: a
      commentary.

PMID- 21887950
TI  - IT and organization: a delicate partnership.
AB  - Information technology (IT) is an important enabler of organization models (OM)
      and of innovative strategies, as it fosters information integration and
      streamlines information flows. Two case studies offer evidence about the
      strategic use of IT innovation (i.e., digital signature) to foster successful OM
      and partnerships in health-care, while results from a survey and some case
      studies show how institutional reforms can foster the diffusion of mature
      technologies (i.e., ERP) as an adaptive strategy of health-care organizations.
      Leadership and clear vision lead to consistency between OM and technology and
      foster the exploitation full benefits associated with innovation.

PMID- 21887951
TI  - Technological iatrogenesis: the manifestation of inadequate organizational
      planning and the integration of health information technology.
AB  - The Institute of Medicine (IOM) views Health Information Technology (HIT) as an
      essential organizational prerequisite for the delivery of safe, reliable, and
      cost-effective health services. However, HIT presents the proverbial double-edged
      sword in generating solutions to improve system performance while facilitating
      the genesis of novel iatrogenic problems. Incongruent organizational processes
      give rise to technological iatrogenesis or the unintended consequences to system
      integrity and the resulting organizational outcomes potentiated by incongruent
      organizational-technological interfaces. HIT is a disruptive innovation for
      health services organizations but remains an overlooked organizational
      development (OD) concern. Recognizing the technology-organizational misalignments
      that result from HIT adoption is important for leaders seeking to eliminate
      sources of system instability. The Health Information Technology Iatrogenesis
      Model (HITIM) provides leaders with a conceptual framework from which to consider
      HIT as an instrument for organizational development. Complexity and Diffusion of
      Innovation theories support the framework that suggests each HIT adoption
      functions as a technological change agent. As such, leaders need to provide
      operational oversight to managers undertaking system change via HIT
      implementation. Traditional risk management tools, such as Failure Mode Effect
      Analysis and Root Cause Analysis, provide proactive pre- and post-implementation
      appraisals to verify system stability and to enhance system reliability.
      Reconsidering the use of these tools within the context of a new framework offers
      leaders guidance when adopting HIT to achieve performance improvement and better
      outcomes.

PMID- 21887952
TI  - HIT management research and the tip of the iceberg: setting a research agenda--a
      commentary.

PMID- 21887953
TI  - E pluribus unum: using group model building with many interdependent
      organizations to create integrated health-care networks.
AB  - This chapter reports on an action research case study of integrated obstetric
      care in the Netherlands. Efficient and patient-friendly patient flows through
      integrated care networks are of major societal importance. How to design and
      develop such interorganizational patient flows is still a nascent research area,
      especially when dealing with a large number (n>3) of stakeholders. We have shown
      that a modification of an existing method to support interorganizational
      collaboration by system dynamics-based group model building (GMB) (the Renga
      method, Akkermans, 2001) may be effective in achieving such collaboration.

PMID- 21887954
TI  - Health-care organizations as "patients": transforming the fundamental od
      paradigm.
AB  - Hidden behind such frequently used phrases as "The system/policy requires...,"
      "The organization has decided..." is one simple fact. Systems/policies don't drop
      from the sky etched in stone tablets and organizations don't decide anything.
      People make decisions and design systems and write policies. Embracing this fact
      increases the likelihood that the provision of health-care emanates from a "care
      dealership" in contrast to a "car dealership." Ignoring this fact leads to less
      humane, less effective, and more costly health-care. This chapter will challenge
      all of us concerned with caring for all of us--from Organizational Development
      (OD). Practitioners to CEOs to ... to ... all of us at some point in our lives-
      to step up to the need to transform our most basic paradigms. To remind ourselves
      that human beings give birth to, nurture, sustain, and care for that which we
      call an organization. In so doing, we will be able to begin to act from the
      premise that a health-care organization is itself a living breathing human
      organism, a "Patient" in need of care. The quality of care we afford this
      "Patient" directly and inevitably impacts the quality of care we are afforded as
      patients. Acting from this premise will transform all of health-care, all "care
      dealerships" ... and potentially "car dealerships" as well. OD professionals,
      therefore, can propel us all to a fourth dimension of caring for all of us.

PMID- 21887955
TI  - Sustaining high performance: dynamic balancing in an otherwise unbalanced system.
AB  - As Ovid said, "There is nothing in the whole world which is permanent." It is
      this very premise that frames the discoveries in this chapter and the compelling
      paradox it has raised. What began as a question of how performance is sustained,
      unveiled a collection of core organizational paradoxes. The findings ultimately
      suggest that sustained high performance is not a permanent state an organization
      achieves, but rather it is through perpetual movement and dynamic balance that
      sustainability occurs. The idea of sustainability as movement is predicated on
      the ability of organizational members to move beyond the experience of paradox as
      an impediment to progress. Through holding three critical "movements"-
      agile/consistency, collective/individualism, and informative/inquiry--not as
      paradoxical, but as active polarities, the organizations in the study were able
      to transcend paradox, and take active steps to continuous achievement in
      outperforming their peers. The study, focused on a collection of hospitals across
      the Unites States, reveals powerful stories of care and service, of the profound
      grace of human capacity, and of clear actions taken to create significant
      results. All of this was achieved in an environment of great volatility, in
      essence an unbalanced system. It was the discovery of movement and ultimately of
      dynamic balancing that allowed the organizations to in this study to move beyond
      stasis to the continuous "state" of sustaining high performance.

PMID- 21887956
TI  - Learning to think systemically about health-care systems: a commentary.

PMID- 21887957
TI  - Organization development in healthcare: conversations on research and strategies.
      Concluding remarks.

PMID- 21887958
TI  - Autobiographical memory development from an attachment perspective: the special
      role of negative events.
AB  - The authors propose a novel model of autobiographical memory development that
      features the fundamental role of attachment orientations and negative life
      events. In the model, it is proposed that early autobiographical memory derives
      in part from the need to express and remember negative experiences, a need that
      has adaptive value, and that attachment orientations create individual
      differences in children's recollections of negative experiences. Specifically,
      the role of attachment in the processing of negative information is discussed in
      regard to the mnemonic stages of encoding, storage, and retrieval. This model
      sheds light on several areas of contradictory data in the memory development
      literature, such as concerning earliest memories and children's and adults'
      memory/suggestibility for stressful events.

PMID- 21887959
TI  - Links between attachment and social information processing: examination of
      intergenerational processes.
AB  - This chapter describes theory and research on intergenerational connections
      between parents' attachment and children's social information processing, as well
      as between parents' social information processing and children's attachment. The
      chapter begins with a discussion of attachment theorists' early insights into the
      role that social information processing plays in attachment processes. Next,
      current theory about the mechanisms through which cross-generational links
      between attachment and social information processing might emerge is presented.
      The central proposition is that the quality of attachment and/or the social
      information processing of the parent contributes to the quality of attachment
      and/or social information processing in the child, and these links emerge through
      mediating processes related to social learning, open communication, gate-keeping,
      emotion regulation, and joint attention. A comprehensive review of the literature
      is then presented. The chapter ends with the presentation of a current
      theoretical perspective and suggestions for future empirical and clinical
      endeavors.

PMID- 21887960
TI  - The development of episodic foresight: emerging concepts and methods.
AB  - Episodic foresight is here defined as the ability to project oneself into the
      future and mentally simulate situations and outcomes. Tasks used to study the
      development of episodic foresight in young children are reviewed and compared to
      tasks used to study other future-oriented abilities (planning, delay of
      gratification, and prospective memory) in the same age-group. We argue for the
      importance of accounting for and minimizing the role of other cognitive demands
      in research tasks. Because episodic foresight is an emerging ability in young
      children, more research needs to be directed at the contexts in which it emerges
      and the extent to which episodic foresight is part of a growing ability for
      mental representation.

PMID- 21887961
TI  - From little white lies to filthy liars: the evolution of honesty and deception in
      young children.
AB  - Though it is frequently condemned, lie-telling is a common and frequent activity
      in interpersonal interactions, with apparent social risks and benefits. The
      current review examines the development of deception among children. It is argued
      that early lying is normative, reflecting children's emerging cognitive and
      social development. Children lie to preserve self-interests as well as for the
      benefit of others. With age, children learn about the social norms that promote
      honesty while encouraging occasional prosocial lie-telling. Yet, lying can become
      a problem behavior with frequent or inappropriate use over time. Chronic lie
      telling of any sort risks social consequences, such as the loss of credibility
      and damage to relationships. By middle childhood, chronic reliance on lying may
      be related to poor development of conscience, weak self-regulatory control, and
      antisocial behavior, and it could be indicative of maladjustment and put the
      individual in conflict with the environment. The goal of the current chapter is
      to capture the complexity of lying and build a preliminary understanding of how
      children's social experiences with their environments, their own dispositions,
      and their developing cognitive maturity interact, over time, to predict their
      lying behavior and, for some, their chronic and problem lying. Implications for
      fostering honesty in young children are discussed.

PMID- 21887962
TI  - A model of moral identity: applications for education.
AB  - The purpose of this chapter is to build an intellectual bridge between moral
      psychology and education. Our hope is that the findings from moral psychology
      will inform and explain best practices in moral education. With that end in mind,
      we briefly and selectively review the moral education and character education
      literature highlighting some of the challenges these domains have faced. Next, we
      review the moral identity literature and offer our own model of moral identity
      formation emphasizing the "characteristic adaptations" (i.e., moral orientation,
      moral self, moral emotions, and social relationships and opportunities) of the
      model. Finally, we illustrate and explain how some of these "characteristic
      adaptations" have been or could be used in the development of successful moral
      education programs, and provide specific examples for application of our model in
      the domain of sex education.

PMID- 21887963
TI  - Cultural patterns in children's learning through keen observation and
      participation in their communities.
AB  - This chapter examines children's learning through careful attention and
      participation in the ongoing activities of their community. This form of
      learning, which has been called learning through Intent Community Participation,
      seems to be especially common in Mesoamerican Indigenous communities. In these
      communities, children are integrated into the everyday work and lives of adults
      and their learning may not be the central focus. We contrast this pattern with
      that of middle-class European American communities where children are segregated
      from the primary adult functions of the community. In middle-class communities
      and schools, children are often encouraged to engage in abstract lessons where
      their attention is explicitly directed to specific events. In contrast, learning
      through keen attention and observation may rely on learning through attention to
      instructions not specifically directed to the learner. Studies demonstrate
      Mesoamerican Indigenous children's ability to learn through simultaneous and open
      attention to overheard or observed activities. This form of learning is supported
      through multiple modalities of communication and interaction. Motivation to learn
      stems from the learner's inclusion into the major activities and goals of the
      community. Implications of research and future directions for the study of
      learning through keen observation are discussed.

PMID- 21887964
TI  - Family relationships and children's stress responses.
AB  - In this chapter, the theoretical and empirical associations between family
      relationships and children's responses to stressors are reviewed. Family
      relationships explored are primarily dyadic, representing the emphasis of past
      empirical research; these include parent-parent, parent-child, and sibling
      relationships. However, in recognition of the more complicated and interconnected
      nature of family relationships, also reviewed are associations between the
      broader family context and children's stress responses. Multiple measures of
      stress responses are considered, including both physiological and emotional
      responses to and recovery from stressful experiences. Overall, the studies
      reviewed suggest that poor-quality family environments, including those
      characterized by low emotional support or high conflict, are associated with
      dysregulated stress responses throughout childhood and adolescence. In contrast,
      children and adolescents in families with high emotional support or low conflict
      seem to be protected from developing stress regulatory problems. Limitations in
      this body of research as well as directions for future research are discussed.

PMID- 21887965
TI  - Developmental perspectives on vulnerability to nonsuicidal self-injury in youth.
AB  - Nonsuicidal self-injury (NSSI) is defined as intentionally causing bodily harm to
      oneself without the intent to kill oneself. Recently, there has been an increase
      in research aimed at understanding why individuals, especially youth and young
      adults, engage in NSSI. This chapter explores the emergence and maintenance of
      NSSI from a developmental perspective. Epidemiological research suggests that
      rates of NSSI increase dramatically from early adolescence to young adulthood. No
      study has investigated NSSI in youth younger than age 10. Current understanding
      of how emotion and cognitions as well as interpersonal processes play a role in
      the emergence and maintenance of NSSI is explored. Further, the role of biology
      (e.g., neurological underpinnings, genetic associations, HPA-axis functioning) on
      NSSI is explored. Throughout the chapter, particular limitations (e.g., sample
      selection, measurement issues) in the extant corpus of knowledge are highlighted.
      Finally, we consider future research directions that may inform developmentally
      sensitive understanding of the proximal and distal risk factors that may affect
      the emergence and maintenance of NSSI across the life span.

PMID- 21887967
TI  - Monitoring, metacognition, and executive function: elucidating the role of self
      reflection in the development of self-regulation.
AB  - While an abundance of research has investigated the development of the automatic
      and controlled processes through which individuals control their thoughts,
      emotions, and actions, less research has emphasized the role of the self in self
      regulation. This chapter synthesizes four literatures that have examined the
      mechanisms through which the individual acts in a managerial role, evaluating the
      current status of the system and initiating regulatory actions as necessary.
      Taken together, these literatures (on executive function, error monitoring,
      metacognition, and uncertainty monitoring) suggest that self-reflection plays a
      critical role in self-regulation, and that developmental improvements in self
      reflection (via increasing levels of conscious awareness and enhanced calibration
      of monitoring systems) may serve as driving forces underlying developmental
      improvement (and temperamental individual differences) in children's ability to
      control their thoughts and actions.

PMID- 21887966
TI  - More similarities than differences in contemporary theories of social
      development?: a plea for theory bridging.
AB  - Many contemporary theories of social development are similar and/or share
      complementary constructs. Yet, there have been relatively few efforts toward
      theoretical integration. The present chapter represents a call for increased
      theory bridging. The problem of theoretical fragmentation in psychology is
      reviewed. Seven highlighted reasons for this predicament include differences
      between behavioral sciences and other sciences, theoretical paradigms as social
      identities, the uniqueness assumption, information overload, field fixation,
      linguistic fragmentation, and few incentives for theoretical integration.
      Afterward, the feasibility of theoretical synthesis is considered. Finally, some
      possible directions are proposed for theoretical integration among five
      contemporary theories of social and gender development: social cognitive theory,
      expectancy-value theory, cognitive-developmental theory, gender schema theory,
      and self-categorization theory.

PMID- 21887968
TI  - New HVs may fail to find work.

PMID- 21887969
TI  - "Trust and culture change are essential to tackle bullying".

PMID- 21887970
TI  - "Why did the chicken cross the road? To escape the cannibal".

PMID- 21887971
TI  - "A plethora of job titles just serve to confuse our patients".

PMID- 21887972
TI  - ECGs 1: how to carry out monitoring.

PMID- 21887973
TI  - How to manage harmful drinking.

PMID- 21887974
TI  - Measuring vital signs: an integrated teaching approach.
AB  - In September 2010, nurse lecturers at the University of the West of Scotland
      introduced a holistic, integrated teaching approach to engage students with
      essential nursing skills. This article discusses how the integrated approach was
      introduced and how it was used to teach students to measure vital signs. It also
      provides an evaluation of the approach and recommendations for further
      development.

PMID- 21887975
TI  - Intentional rounding: its role in supporting essential care.
AB  - The King's Fund Point of Care (POC) programme aims to identify and test
      interventions that can improve patients' experiences of care. "Intentional
      rounding" is one such intervention, which is being trialled by some of the teams
      working with the King's Fund on the POC programme. This article explains the
      principles of intentional rounding and how nurses can use it to ensure patients'
      essential care needs are met.

PMID- 21887976
TI  - Collaboration to transform care.
AB  - Transforming Care is an improvement initiative introduced at Betsi Cadwaladr
      University Health Board in October 2010. The health board collaborated with a
      university to develop a degree module to support its implementation. This article
      describes the delivery and evaluation of the module, and how Transforming Care is
      helping to unite a newly formed organisation.

PMID- 21887977
TI  - Care at the top.

PMID- 21887978
TI  - Be seen as a leader--behave as one.

PMID- 21887979
TI  - At least in Cook County we can talk to officials about access to care.

PMID- 21887980
TI  - Examining HIPAA's disclosure exceptions.
AB  - HIPAA was enacted to protect the rights and privacy of patients. However,
      healthcare providers should be aware that there are disclosure exceptions without
      first obtaining the patient's permission. These exceptions are well defined and
      explained in the document referenced in this case study.

PMID- 21887981
TI  - Preserve your profit.

PMID- 21887982
TI  - Protect your practice before you sign an agreement with an independent
      contractor.

PMID- 21887983
TI  - Farewell, food pyramid.

PMID- 21887984
TI  - What you should know about dental X-rays.

PMID- 21887985
TI  - Will paying more produce better quality?

PMID- 21887987
TI  - Therapeutic substitution. A change for the good--or the bad?

PMID- 21887988
TI  - As ACOs grow, new payment models explored.

PMID- 21887986
TI  - Has Medicare gone too far to control imaging costs?

PMID- 21887989
TI  - Health plans seek leverage when physicians submit extremely high bills.

PMID- 21887990
TI  - Will mental health's 'bible' make believers of insurers?

PMID- 21887991
TI  - Health plans cannot ignore Express Scripts-Medco deal.

PMID- 21887992
TI  - Nurses join the executive pool.

PMID- 21887993
TI  - Outcomes and costs associated with initial maintenance therapy with fluticasone
      propionate-salmeterol xinafoate 250 microg/50 microg combination versus
      tiotropium in commercially insured patients with COPD.
AB  - PURPOSE: To compare, in commercially-insured individuals 240 years old, the risk
      of chronic obstructive pulmonary disease (COPD) exacerbations and COPD-related
      health care utilization and costs in patients initiating maintenance treatment
      with fluticasone propionate/salmeterol xinafoate 250 microg/50 microg (FSC) with
      those in patients initiating treatment with tiotropium bromide (TIO). DESIGN:
      Retrospective observational cohort study. METHODOLOGY: The risk of COPD
      exacerbation (moderate, severe, and any), COPD-related health care utilization,
      and COPD-related costs (overall and by service setting) were assessed over 12
      months after the initiation of treatment with FSC or TIO in commercially-insured
      patients > or =40 years old diagnosed with COPD. PRINCIPAL FINDINGS: After
      adjusting for covariates, treatment with FSC compared with treatment with TIO was
      associated with a 14% reduction in risk of severe exacerbation (p = 0.0406),
      defined as the occurrence of a COPD-related hospitalization; with less health
      care utilization across several categories of care; with 25% lower COPD-related
      medical costs ($1814 versus $2258 per patient, p < 0.0001); and with 10% lower
      COPD-related total costs ($2991 versus $3304 per patient, p < 0.0001) over a 12
      month follow-up period. Pharmacy costs were equivalent between FSC and TIO.
      CONCLUSION: Initiation of maintenance therapy with FSC compared with TIO was
      associated with significant reductions in the risk of severe exacerbations,
      health care utilization, and COPD-related medical and total costs. Considered in
      the context of other findings, these data suggest that earlier maintenance
      treatment with FSC offers clinical and economic benefits over maintenance
      treatment with TIO.

PMID- 21887994
TI  - Part D reduces hospitalizations for some conditions.

PMID- 21887996
TI  - Employers look far and wide to reduce expenses.

PMID- 21887995
TI  - Teaching the teachers means better doc visits?

PMID- 21887997
TI  - Modeling initiation into drug injection among street youth.
AB  - This study aimed at examining the predictors of initiation into drug injection
      among street youth using social cognitive theory framework. A prospective cohort
      study based on semi-annual interviews was carried out. Psychosocial determinants
      referred to avoidance of initiation. Other potential predictors were:
      sociodemographic characteristics, relationships with injectors, parent's
      substance misuse, drug use patterns, homelessness, survival sex, sexual abuse.
      Independent predictors were identified using Cox proportional hazards regression
      models. Among the 352 participants, high control beliefs about avoidance of
      initiation was protective while younger age, daily alcohol consumption, heroin
      use, cocaine use, and survival sex all increased risk of initiation. Preventive
      strategies targeting street youth should both enhance youth's control beliefs and
      actual control over their substance use and improve their life conditions.

PMID- 21887998
TI  - Tobacco prevention education in schools for the deaf: the faculty perspective.
AB  - We report results of a survey of tobacco education practices and perspectives
      among faculty at four Schools for the Deaf participating in the trial of a
      tailored tobacco prevention curriculum. Few faculty (20.4%) included tobacco use
      among the three most important health problems facing their students, although
      88.8% considered tobacco education to be worthwhile. Despite perceived unmet
      needs among their students, classroom or school-wide attention to tobacco
      prevention was limited. Only 13.9% reported delivering tobacco programming in the
      prior year, most often reporting lack of deaf-friendly curriculum and materials
      (60.9%), time (47.8%), and training (43.5%) as barriers to program delivery.
      Perceptions, attitudes, and institutional issues, including lack of tailored
      curriculum, were seen as contributing to the limited focus on this important
      health problem.

PMID- 21887999
TI  - Neighborhood perceptions and parent outcomes in family based prevention programs
      for Thai adolescents: the role of program engagement.
AB  - Due to concerns over Thai adolescent risky behaviors, effective prevention
      strategies are needed. Determining the role neighborhood context plays in program
      engagement and outcomes may inform these strategies. This study includes 170
      mother-adolescent pairs (M = 13.44, SD = .52) in Bangkok, Thailand in a
      prevention program for adolescent substance use and sexual risk. Neighborhoods
      were related to engagement, which was critical to outcomes. Neighborhood
      disorganization was related to confidence in program effects and program
      completion. Completion was related to increased ATOD communication. Neighborhood
      cohesion was related to less program enjoyment, while neighborhood social control
      was related to more enjoyment. Enjoyment was related to increased ATOD
      communication and formation and monitoring of alcohol rules. Prevention
      strategies should focus on neighborhood contexts and enhancing engagement.

PMID- 21888000
TI  - Polysubstance use patterns in underground rave attenders: a cluster analysis.
AB  - Drug use in mainstream rave parties has been widely documented in a large number
      of studies. However, not much is known about drug use in underground raves. The
      purpose of this study is to find out the polysubstance use patterns at
      underground raves. Two hundred and fifty-two young people between the ages of 18
      and 30 who went to underground raves were interviewed. They were given a
      questionnaire to collect information on drug use at raves. Ravers used a mean of
      4.9 different drugs at the last rave they had been to. Over 75% of them used
      tobacco, alcohol, cannabis, and amphetamine, and over half also used powder
      ecstasy. Two differentiated use patterns were found: one pattern concentrated
      more on the use of stimulants and the other on the use of hallucinogens.
      Underground ravers have a "standard" sociodemographic profile. The use of drugs
      is much higher than equivalent age group. Higher drug use prevalence than in
      mainstream rave parties is also observed. Different patterns of use appear which
      will be necessary to consider in designing preventions and risk reduction
      strategies,

PMID- 21888002
TI  - Nursing inquiry to address pressing empirical and ethical questions.

PMID- 21888001
TI  - Preferred drug resistance strategies of urban American Indian youth of the
      southwest.
AB  - This study explored the drug resistance strategies that urban American Indian
      adolescents consider the best and worst ways to respond to offers of alcohol,
      cigarettes, and marijuana. Focus group data were collected from 11 female and 9
      male American Indian adolescents attending urban middle schools in the southwest.
      The youth were presented with hypothetical substance offer scenarios and
      alternative ways of responding, based on real-life narratives of similar youth.
      They were asked to choose a preferred strategy, one that would work every time,
      and a rejected strategy, one they would never use. Using eco-developmental
      theory, patterns in the preferred and rejected strategies were analyzed to
      identify culturally specific and socially competent ways of resisting substance
      offers. The youth preferred strategies that included passive, non-verbal
      strategies like pretending to use the substance, as well as assertive strategies
      like destroying the substance. The strategies they rejected were mostly socially
      non-competent ones like accepting the substance or responding angrily. Patterns
      of preferred and rejected strategies varied depending on whether the offer came
      from a family member or non-relative. These patterns have suggestive implications
      for designing more effective prevention programs for the growing yet underserved
      urban American Indian youth population.

PMID- 21888003
TI  - Fostering social justice: the possibilities of a socially connected model of
      moral agency.

PMID- 21888004
TI  - Advance care planning: re-visioning our ethical approach.
AB  - This qualitative study explored the applicability and usefulness of a promising
      advance care planning (ACP) intervention and examined the ACP process. Nine dyads
      (patients newly diagnosed with advanced lung cancer and a family member)
      participated in the ACP intervention, with evaluative interviews at 3 and 6
      months after the intervention. All interviews were recorded, transcribed
      verbatim, and analyzed using constant comparison. The process was found not to be
      one of preparing a substitute decision-maker to speak for oneself and direct
      health care at a time when one is incapacitated; rather, the families engaged in
      a deeply relational process where meaning, values, and preferences were
      negotiated in conversation. ACP is theoretically rooted in a traditional notion
      of patient autonomy that is not aligned with the relational process that unfolded
      in this study. An approach that embraces relational autonomy is more congruent
      and provides a stronger foundation for meeting the needs of families.

PMID- 21888005
TI  - Remote nursing certified practice: viewing nursing and nurse practitioner
      practice through a social justice lens.
AB  - Remote Nursing Certified Practice (RNCP) was introduced in 2010 to regulate
      nursing practice in remote, largely First Nations communities in British
      Columbia, Canada. These are communities that often experience profound health and
      health-care inequities. Typically nurses are the main health-care providers.
      Using a critical social justice lens, the authors explore the clinical and
      ethical implications of RNCP in terms of access to equitable, high-quality
      primary health care.They examine the fit between the level and scope of health
      services provided by registered nurses working under RNCP and the health needs of
      remote First Nations communities. In doing so, they draw comparisons between
      nurse practitioners (NPs) and outpost nurses working in NP roles who historically
      were employed to provide health care in these communities.The authors conclude by
      calling for nursing regulations that support equitable, high-quality primary care
      for all British Columbians.

PMID- 21888006
TI  - International research collaboration as social relation: an Ethiopian-Canadian
      example.
AB  - International collaboration in nursing and other health disciplines is vital for
      addressing global health issues. While the results and processes of such
      collaborations have been reported, few publications have addressed their
      philosophical or theoretical underpinnings, particularly with respect to
      collaboration between those in low- and high-income countries. Piaget's notion of
      social relations of cooperation and constraint and Habermas's notion of
      "lifeworld" provide a theoretical lens through which to examine international
      collaboration as a construction of knowledge. This article is an exploration of
      these ideas as seen in the collective experience of Canadians and Ethiopians
      organizing an interdisciplinary forum on intimate partner violence in Ethiopia.
      The project is presented as a case study for reflecting on international
      collaboration as a manifestation of social relations. Such re-visioning of
      international collaboration may be useful for improving collaborative processes
      and their outcomes.

PMID- 21888007
TI  - Patients' perceptions of individualized care: evaluating psychometric properties
      and results of the individualized care scale.
AB  - Health-care organizations aim to provide patient-centred care, yet measurement of
      this aspect of care quality remains a challenge.This cross-sectional study
      investigated the reliability and validity of the bipartite Individualized Care
      Scale (ICSA, ICS-B) in a Canadian hip and knee arthroplasty population. Internal
      consistency of the ICS-A and ICS-B was high; however, factorial validity was not
      fully supported. Twenty-five percent of participants provided additional open
      ended comments to describe individual perceptions, needs, and suggestions, noting
      that the Likert-scale approach required them to aggregate their feedback about
      rather than share their perceptions of individual nurses.The findings indicate
      that it is important to patients to be able to share their individual stories
      when evaluating nursing care. Future qualitative studies should examine the nurse
      perspective on the provision of patient-centred care, including investigation of
      systems and process-related features that foster or hinder more individualized
      care.

PMID- 21888008
TI  - Platelet microRNA profiles and the effect of pathogen reduction on platelet
      function.

PMID- 21888009
TI  - Biomarkers for the prediction of mortality and morbidity in patients with renal
      replacement therapy.
AB  - The mortality of end-stage renal disease (ESRD) patients on dialysis remains high
      despite great improvement of dialysis technologies in the past decades. These
      patients die due to infectious diseases (mainly sepsis), cardiovascular diseases
      such as myocardial infarction, heart failure, stroke, and, in particular, sudden
      cardiac death. End stage renal disease is a complex condition, where the failure
      of kidney function is accompanied by numerous metabolic changes affecting almost
      all organ systems of the human body. Many of the biomarker characteristics of the
      individually affected organ systems have been associated with adverse outcomes.
      These biomarkers are different in patients with ESRD compared to the general
      population in the prediction of morbidity and mortality. Biomarker research in
      this field should aim to identify patients at risk for the different disease
      entities. Traditional biomarkers such as CRP, BNP, and troponins as well as new
      biomarkers such as fetuin, CD154, and relaxin were analyzed in patients on
      dialysis. We will include observational as well as prospective clinical trials in
      this review. Furthermore, we will also discuss proteomics biomarker studies. The
      article assess the potential diagnostic value of different biomarkers in daily
      clinical practice as well as their usefulness for clinical drug development in
      end stage renal disease patients.

PMID- 21888010
TI  - Peroxisomal biogenesis disorder biomarkers.
AB  - BACKGROUND: The pathological mechanisms underlying peroxisomal biogenesis
      disorders (PBD) are not fully understood and the available therapies are not
      sufficient. This stresses the importance of identifying biochemical markers that
      reflect the extent of peroxisomal dysfunction in plasma of PBD patients. METHODS:
      Very long chain fatty acids VLCFAs, Phytanic acid, inflammatory markers: tumor
      necrosis-alpha, interleukin-6, and interleukin-2 (TNF-alpha, IL-6, and IL-2),
      lipid peroxidation parameter malonedialdhyde (MDA), low density lipoprotein
      cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), and catalase
      activity were measured. RESULTS: Significant increases in LDL-C, VLCFAs (C26:0,
      C26:0/C22:0 and C24:0/C22:0), Phytanic acid, MDA, and Catalase were observed
      along with significant decreases in Plasmalogen and HDL-C level. No significant
      difference could be found between male and female patients regarding the
      biochemical parameters. Both cholesterol and triglycerides showed no significant
      difference between patients and controls. The characteristic curve (ROC) showed
      that VLCFAs were the most significant diagnostic markers for PBD followed by TNF
      alpha, IL2, IL6, MDA, and plasmalogens. CONCLUSIONS: PBD patients have impaired
      anti-oxidative defense together with increased inflammatory markers. We provide
      biomarkers that could guide therapies and prevention strategies. Based on our
      results we suggest clinical trials to investigate the role of dietary
      supplementation of antioxidants such as vitamin C and E as an adjuvant therapy
      for PBD patients.

PMID- 21888011
TI  - An evaluation of the performance of a novel stick-type kit for rapid detection of
      Helicobacter pylori antibodies in urine.
AB  - BACKGROUND: ODK-0702 is a stick-type urinary Helicobacter pylori (H. pylori)
      antibodies detection kit, developed to improve the original housing type urinary
      H. pylori antibodies detection kit "RAPIRUN H. pylori Antibody". This stick-type
      kit is designed for the efficient daily medical practice at hospital or clinic,
      public or school health checkup, to detect H. pylori infection. The aim of this
      study was to evaluate the performance and correlation of this kit with the
      original kit and the ELISA kit. METHODS: Control kits were "RAPIRUN H. pylori
      Antibody" (Kit A) and "URINELISA H. pylori Antibody" (Kit B). Urine samples were
      obtained from 249 subjects scheduled for upper endoscopy, 99 subjects suspected
      of having upper gastrointestinal disease, and 150 subjects receiving health
      checkups. Rates of agreement in results between ODK-0702 and the control kits
      were investigated. RESULTS: High agreement rates of 98.4% (245/249) and 88.8%
      (221/249) were found between ODK-0702 and the kits, Kit A and B, respectively. In
      patients, the agreement rates of ODK-0702 as compared to Kit A and B were 99.0%
      (98/99) and 88.9% (88/99), respectively. In control subjects, the agreement rates
      of ODK-0702 as compared to Kit A and B were 98.0% (147/150) and 88.7% (133/150),
      respectively. CONCLUSIONS: ODK-0702 enabled rapid testing within 15 minutes and
      showed equivalent performance as control kits, being clinically very useful in
      the diagnosis of H. pylori infection.

PMID- 21888012
TI  - Inactivation of herpes simplex virus type 1 & adenovirus type 5 by direct
      electric current at a biocompatible level in vitro.
AB  - BACKGROUND: In vitro studies were conducted to quantify the effectiveness of low
      level direct electric current (DC) on infectivity of Herpes Simplex Virus type 1
      (HSV-1), Adenovirus type 5 (AdV-5), and on viability of Vero cells. METHODS: Both
      viruses and Vero cells were exposed to DC by using platinum electrodes connected
      to a DC source, then the viral infectivity and cell viability were assessed by
      plaque and MTT assay, respectively. RESULTS: The results showed that both viruses
      were inactivated completely by 200 microA DC in 10 minutes (current density = 20
      microA/mm2) while this amount of DC had no significant changes on the viability
      of Vero cells (viability > 90 %). Inactivation degree of HSV-1 and AdV-5 was 5
      and 4 log per mL, respectively. Further study is required to investigate the
      mechanism of inactivation by this method. CONCLUSIONS: DC at a biocompatible
      level showed the competency to inactivate the viruses in the solution completely.
      So it is a useful tool for designing a noninvasive method for decontamination of
      biological or synthetic fluids. This method or derivation can be considered as an
      easy, fast, and economical method for fluid decontamination.

PMID- 21888013
TI  - Clinical usefulness of the semiquantitative procalcitonin test in the diagnosis
      of bacterial infections in a third level children's hospital.
AB  - BACKGROUND: The differential diagnosis between viral and bacterial infections can
      be challenging in children. Procalcitonin (PCT) has been investigated as an early
      marker for bacterial infections. The aim of this study was to assess the
      usefulness of procalcitonin (PCT) compared to C-reactive protein (CRP), white
      cell blood count (WBC), and absolute neutrophil count (ANC) for differentiating
      bacterial from viral infections in a third level pediatric hospital. METHODS:
      Children admitted for a clinically suspected infection to the Pediatric Clinic
      from January 1, 2005 to December 31, 2008, who had concurrent evaluation of PCT,
      CRP, WCB, and ANC were included in the study. According to the diagnosis at
      discharge based on the ICD-9 codes, patients were classified into two groups:
      children with certain bacterial infections (CBI) and children with certain viral
      infections (CVI). PCT concentrations were determined by semiquantitative PCT-Q
      strips. The diagnostic performance of the markers were studied by receiver
      operating characteristic (ROC) analysis. Logistic regression analysis was used to
      evaluate the risk of bacterial infection in relation to all the study markers.
      RESULTS: Among the 165 children included in the study PCT sensitivity was the
      same as CRP (60.56% vs 66.19%; p = 0.646) while PCT specificity was lower (77.27%
      vs 88.18%; p = 0.050) in the detection of bacterial infections. CONCLUSIONS: The
      PCT semiquantitative test is not sufficiently sensitive to be used alone as a
      marker of bacterial infection.

PMID- 21888014
TI  - Renoprotective effects of combined endothelin-converting enzyme/neutral
      endopeptidase inhibitor SLV338 in acute and chronic experimental renal damage.
AB  - BACKGROUND: Acute kidney injury (AKI) as well as chronic renal failure are
      associated with a huge mortality/morbidity. However, so far no drugs have been
      approved for the treatment of acute kidney failure and only a few for the
      treatment of chronic kidney disease (CKD). We analysed the effect of SLV338, a
      neutral endopeptidase (NEP)/endothelin converting enzyme (ECE)-inhibitor in
      animal models of acute kidney failure as well as chronic renal failure. METHODS:
      Acute renal failure was induced in male Wistar rats by uninephrectomy and
      clamping of the remaining kidney for 55 minutes. SLV338 (total dose: 4.9 mg/kg)
      or vehicle was continuously infused for 2 hours (starting 20 minutes prior to
      clamping). Sham operated animals served as controls. Plasma creatinine was
      measured at baseline and day 2 and 8 after renal ischemia-reperfusion.
      Hypertensive renal damage was induced in male Sprague Dawley rats by nitric oxide
      deficiency using L-NAME (50 mg/kg per day, added to drinking water for 4 weeks).
      One group was treated over the same time period with SLV338 (30 mg/kg per day,
      mixed with food). Systolic blood pressure was monitored weekly. At study end,
      urine and blood samples were collected and kidneys were harvested. RESULTS: Acute
      renal ischemia-reperfusion caused a 5-fold plasma creatinine elevation (day 2),
      which was significantly attenuated by more than 50% in animals treated with
      SLV338 (p < 0.05). Renal failure was accompanied by a 67% mortality in vehicle
      treated rats, but only 20% after SLV338 treatment (p = 0.03 compared to sham
      controls). Chronic L-NAME administration caused hypertension, urinary albumin
      excretion, glomerulosclerosis, renal arterial remodelling, and renal interstitial
      fibrosis. Treatment with SLV338 did not significantly affect blood pressure, but
      abolished renal tissue damage (interstitial fibrosis, glomerulosclerosis, renal
      arterial remodelling (p < 0.05 versus L-NAME group in each case). CONCLUSIONS:
      The dual ECE/NEP inhibitor SLV338 preserves kidney function and reduces mortality
      in severe acute ischemic renal failure. Moreover, combined ECE/NEP inhibition
      prevents hypertensive renal tissue damage in a blood pressure independent manner
      in L-NAME-treated rats.

PMID- 21888015
TI  - HbA(1c) levels in cardiovascular diseased patients without diabetes in a
      developing country.
AB  - BACKGROUND: High levels of glycated hemoglobin (HbA(1c)) have been associated
      with Coronary Vascular Diseases (CVD) in diabetic patients. Recent studies have
      reported no association between elevated glycated hemoglobin (HbA(1c)) and
      incident cardiovascular disease (CVD) among women without diabetes. There are
      many controversial studies on topics such as "Glycated hemoglobin levels
      (HbA(1c)) have been associated with cardiovascular diseases (CVD) in the non
      diabetic patients". Therefore, we planned this study. METHODS: The present study
      was conducted on 50 age matched controls and 50 clinically diagnosed non-diabetic
      CVD patients of either gender. The study included 50 patients with myocardial
      infarction (MI) admitted to the ICCU ward of J.L.N. Medical College and Hospital,
      Ajmer (Rajasthan). The following information was recorded from admission sheets
      of non-diabetic CVD patients of either gender: history of diabetes, hypertension,
      and cigarette smoking; demographic indices; coronary heart disease and diabetes
      mellitus treatment; serum cholesterol; serum triglycerides (TG); high density
      lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C);
      fasting and non-fasting blood glucose levels and Glycated haemoglobin levels
      (HbA(1c)). Glycosylated hemoglobin (HbA(1c)) was measured by latex agglutination
      inhibition assay. RESULTS AND CONCLUSIONS: The HbA(1c) levels in healthy controls
      (n = 50) and non-diabetic CVD subjects (n = 50) observed were 4.32 +/- 0.34% and
      5.80 +/- 0.20%, respectively. HbA(1c) levels in these subjects were significantly
      higher than controls (p < 0.001). The HbA(1c) levels in non-diabetic CVD patients
      are higher in comparison to controls.

PMID- 21888016
TI  - Centrifugation after irradiation of red blood cells does not accelerate
      haemolysis.
AB  - BACKGROUND: For intrauterine transfusion and some other rare indications,
      irradiation and washing or adjustment to an elevated haematocrit is necessary. No
      data are currently available indicating whether irradiation of red blood cell
      concentrates (RBCs) might impair the mechanical stability of erythrocytes during
      centrifugation leading to elevated haemolysis. Consequently, if irradiation and
      centrifugation of RBCs is necessary, there is no definitive recommendation about
      the preferred sequence of steps. METHODS: We divided 20 RBC units that were not
      older than 9 days into two subunits. These subunits were prepared to yield
      irradiated RBCs with an elevated haematocrit, as they are used for intrauterine
      transfusion. One subunit was centrifuged and then irradiated, the other subunit
      was irradiated and then centrifuged. The units were evaluated in vitro before
      preparation and on days 1 and 7. RESULTS: We could not find any difference in the
      haemolysis rate, extracellular LDH or alpha-HBDH between the two groups of RBCs.
      This observation indicates that centrifugation after irradiation of RBCs does not
      accelerate haemolysis. A similar ATP content in the two subunits demonstrated no
      difference in energy metabolism. The extracellular potassium concentration was
      significantly lower in the subunits washed after irradiation. CONCLUSIONS: There
      is no difference in the haemolysis caused by centrifugation between irradiated
      and non-irradiated RBCs. However, it is well known that washing RBCs after
      irradiation significantly lowers the potassium content. Summarising these two
      findings leads to the conclusion that it is optimal first to irradiate and then
      to wash RBCs.

PMID- 21888017
TI  - Platelet reactivity in chronic venous insufficiency.
AB  - BACKGROUND: Chronic venous insufficiency (CVI) is a common medical problem that
      may result in significant morbidity and mortality. Platelets are key players in
      haemostasis and thrombosis, but their role in the development of venous
      thrombosis is more controversial. AIM: The purpose of this study was to
      investigate platelet properties in CVI and their interaction with the venular
      endothelium. METHODS: Human peripheral venules were explanted during leg surgery
      of patients with CVI and of healthy subjects (C); concurrently, the platelets
      were isolated from blood samples collected. The techniques used were:
      fluorescence and electron microscopy and Western-blotting. RESULTS: Compared with
      the C group, the platelets of patients with CVI are activated, as demonstrated
      by: (i) cellular modifications, such as alteration of the discoidal shape by the
      development of extended cytoplasmic filopodia and changes of the cells normal
      ultrastructure, (ii) biochemical modifications, such as the enhanced protein
      levels of FAK, p85 PI3K, Akt and src, accounting for activation of alphaIIbbeta3
      outside-in signaling, and (iii) apparent higher adhesion to the venular
      endothelium. We demonstrate in addition, that CVI is accompanied by severe
      modifications of the ultrastructure of the cells within the venular wall.
      CONCLUSIONS: In CVI, platelets circulate in an activated state and may contribute
      to the altered dysfunctional response of the venous wall and to the development
      of this pathology.

PMID- 21888018
TI  - Cathepsin B, D, and L regulation in cyclosporin A-mediated gingival hyperplasia
      of a patient with sarcoidosis.
AB  - BACKGROUND: Cyclosporin A (CsA) is an immunosuppressant with side effects
      including gingival hyperplasia. Sarcoidosis is a systemic disease characterized
      by granulomas. Here, we report on a rare case of sarcoidosis with gingival
      hyperplasia to clarify whether clinical observation corresponds to in vitro
      results. METHODS: Gingival fibroblasts (HGFs) were isolated from healthy gingiva
      and cultured with CsA. Total RNA was collected and expression of mRNAs examined
      using semi-quantitative RT-PCR analysis. Cathepsin B, D, and L expression in
      overgrown gingiva of the patient was examined by immunohistochemistry. RESULTS:
      Cathepsin D, L, and vascular endothelial growth factor (VEGF)165 mRNA were
      markedly suppressed in CsA-treated HGFs, whereas cathepsin B, matrix
      metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1)
      mRNA were not reduced. Next, the decrease of cathepsin B and L expression in
      enlarged gingiva was observed, whereas an increase of cathepsin D expression was
      observed. Clinically, the enlarged gingival lesions were fully resolved by
      performing oral infection control. CONCLUSIONS: Cathepsins regulation might be an
      important factor in the development of CsA-mediated gingival hyperplasia.

PMID- 21888019
TI  - Effect of a chloride channel inhibitor, 5-nitro-2-(3-phenylpropylamino)-benzoate,
      on ovarian cancer cell migration.
AB  - BACKGROUND: Chloride channels (ClC) are involved in normal physiological
      processes and pathology of various diseases. Although it is recognized that
      suppression of ClC inhibits cell proliferation in different types of cells, the
      potential function of ClC in cell migration in ovarian cancer is still unclear.
      In this study, we investigated the effect of the ClC inhibitor, 5-nitro-2-(3
      phenylpropylamino)-benzoate (NPPB), on cell migration in the human ovarian cancer
      cell line SKOV-3 as well as the related signaling pathway involved in this
      action. METHODS: In this study, cell viability was measured using the MTT assay.
      Transwell migration method was used to study the effect of NPPB on serum-induced
      SKOV-3 cell migration. Also, Western blot was performed to detect the
      phosphorylation levels of ERK1/2 and AKT1 after treatment with NPPB. RESULTS:
      Both NPPB and LY249002 significantly inhibited serum-induced SKOV-3 cell
      migration without alteration of cell viability. NPPB's inhibition of
      phosphorylation of AKT1 was time-dependent (p < 0.05). There was no significant
      effect on the phosphorylation of ERK1/2 after treatment with NPPB. CONCLUSIONS:
      ClC plays an important role in ovarian cancer cell migration. NPPB inhibited-SKOV
      3 cell migration could be via inactivation of AKT1.

PMID- 21888020
TI  - Lipid peroxidation and parathyroid hormone influence the cytosolic calcium levels
      of erythrocytes in peritoneal dialysis patients.
AB  - BACKGROUND: The aim of this study was to examine the alterations in calcium and
      lipid peroxidation in red blood cells (RBCs) and serum samples of continuous
      ambulatory peritoneal dialysis (CAPD) patients. We also investigated the
      relationship between parathyroid hormone (PTH) and calcium homeostasis in this
      study. METHODS: For this purpose, routine blood counts and blood chemistry were
      analyzed by standard laboratory procedures in serum samples. The concentration of
      TBARS was measured in erythrocytes and serum samples. RBC calcium was measured by
      Fura-2AM in a spectrofluorometer. RESULTS: In CAPD patients, hemoglobin, albumin,
      and high density lipoprotein cholesterol levels were lower, but glucose, very low
      density lipoprotein cholesterol, triglyceride, magnesium, PTH, sensitive C
      reactive protein, and uric acid levels were higher than the controls.
      Thiobarbituric acid-reactive substance (TBARS) levels in RBCs and serum samples
      and cytosolic calcium in RBCs were all found to be significantly increased in
      CAPD patients compared to control subjects. Multiple regression analysis showed
      that RBC TBARS and serum PTH were the independent predictors of RBC calcium in
      our study. CONCLUSIONS: Our results confirm that oxidative stress is an important
      risk factor for CAPD. The results of multiple regression analysis suggest that
      RBC calcium was affected by both increased levels of TBARS and PTH.

PMID- 21888021
TI  - Evaluation of status of calcium, magnesium, potassium, and sodium levels in
      biological samples in children of different age groups with normal vision and
      night blindness.
AB  - BACKGROUND: The most common cause of blindness in developing countries is vitamin
      A deficiency. The World Health Organization (WHO) estimates 13.8 million children
      have some degree of visual loss related to vitamin A deficiency. 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 biological sample composition.
      Vitamin and mineral deficiency prevents more than two billion people from
      achieving their full intellectual and physical potential. METHODS: This study was
      designed to compare the levels of magnesium (Mg), calcium (Ca), potassium (K),
      and sodium (Na) in scalp hair, serum, blood, and urine of night blindness
      children in two age groups, (1-5) and (6-10) years, of both genders 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 Mg, Ca,
      K, and Na in biological samples of children with night blindness. The proposed
      method was validated by using conventional wet digestion and certified reference
      samples of hair, serum, blood, and urine. The digests of all biological samples
      were analysed for Mg, Ca, K, and Na by flame atomic absorption spectrometry
      (FAAS) using an air/acetylene flame. RESULTS: The results indicated significantly
      lower levels of Mg, Ca, and K in the biological samples (blood, serum, and scalp
      hair) of male and female children with night blindness and higher values of Na
      compared with control subjects of both genders. CONCLUSIONS: These data present
      guidance to clinicians and other professionals investigating deficiency of
      essential mineral elements in biological samples (scalp hair, serum, and blood)
      of children with night blindness.

PMID- 21888022
TI  - Effects of selenium supplementation on iodine and thyroid hormone status in a
      selected population with goitre in Pakistan.
AB  - BACKGROUND: Selenium (Se) has an essential role in thyroid hormone metabolism. It
      has the potential to play a major part in the outcome of iodine (I) deficiency
      The aim of the present study was to evaluate the Se and I status of biological
      samples (serum and urine) of 160 goitrous male (GMPs) and 195 female patients
      (GFPs). The supplemental effects of Se (200 microg/day) and I (100 - 125
      microg/day) were evaluated after 6 months. For comparison purposes, non-goitrous
      subjects of both genders (n = 440) with same age group and socioeconomic status
      were also selected. METHODS: Hydride generation atomic absorption spectrometry
      (HGAAS) was used to investigate the Se concentration in the biological samples,
      prior to microwave assisted acid digestion. Quality control for the methodology
      was established by comparing the results obtained with certified samples with
      those obtained by conventional wet acid digestion method on the same CRMs and
      real samples. RESULTS: The mean serum Se concentration was significantly lower,
      while urinary Se was higher in GMPs and GFPs as compared to control subjects (p <
      0.005 and < 0.007, respectively). The levels of I, free tri-iodothyronine, and
      thyroxin were found in goitrous patients of both genders were low compared to age
      matched healthy controls (p < 0.015, < 0.006, and < 0.002, respectively). On the
      other hand, high levels of thyroid stimulating hormone were observed in GMPs and
      GFPs (p < 0.009). CONCLUSIONS: It was observed that Se in biological samples of
      hypothyroid patients can play an important role in determining the severity of
      the hypothyroidism associated with iodine deficiency. A wide-scale
      epidemiological study is recommended together with the examination of the
      potential preventive role of Se supplementation in endemic goiter regions.

PMID- 21888023
TI  - Model predicting survival/exitus after traumatic brain injury: biomarker S100B
      24h.
AB  - BACKGROUND: The enigma of Traumatic Brain Injury (TBI), reflected in recent
      scientific literature, is its uncertain consequences, variability of the final
      prognosis with apparently similar TBI, necessity for peripheral biomarkers, and
      more specific predictive models. OBJECTIVES: To study the relationship between
      serum S100B and survival in TBI patients in various serious situations; the S100B
      level in patients without traumatic pathology or associated tumour, subjected to
      stressful situations such as neurological intensive care unit (NICU) stay; the
      possible overestimation caused by extracerebral liberation in TBI patients and
      associated polytraumatism; the predictive cutoffs to determine the most sensitive
      and specific chronology; and achieve a predictive prognostic model. METHODS:
      Patients admitted to the NICU within 6 hours after TBI were selected. We
      measured: a) clinical: exitus yes/no; age and gender, traumatic mechanism,
      polytraumatism yes/no, GCS score, unconsciousness duration, amnesia duration,
      neurological focality, and surgical interventions; b) radiological: CT scan for
      radiological lesions; c) biochemical: serum SB100B at 6, 24, 48 and 72 hours
      after TBI and drug abuse detected in the urine; d) GOS on hospital discharge.
      RESULTS: N: 149 TBI patients, independent of polytraumatism, mean serum S100B at
      6, 24, 48, and 72 hours: 2.1, 1.3, 1.2, and 0.6 microg/L, respectively; N: 124
      without associated polytraumatism, S100B at 6, 24, 48, and 72 hours: 2.0, 1.4,
      1.3, and 0.6 microg/L; N: 50 control I S100B 24 hours: 0.17 microg/L (0.04 -
      0.56) and 25 healthy subjects S100B 0.057 microg/L (0.02-0.094). CONCLUSIONS:
      Significantly higher S100B levels are observed on exitus, with excellent TBI
      prognosis and evolution performance. Hospital stay in the NICU produces
      significant increases in S100B compared to healthy subjects, without invalidating
      it as a biomarker. Polytraumatism associated to TBI does not significantly alter
      S100B levels. S100B at 24 hours > or = 0.90 microg/L appears to predict
      unfavourable TBI evolution with a NPV: 94.2% and PPV: 54.9%. We propose a
      predictive model when we associate S100B at 24 hours with amnesia duration over
      30 minutes with a NPV of 85.5% and a PPV of 83.3%.

PMID- 21888024
TI  - The influence of 7-OH methotrexate metabolite on clinical relevance of
      methotrexate determination.
AB  - BACKGROUND: A modified high performance liquid chromatographic (HPLC) method has
      been developed for the simultaneous determination of methotrexate (MTX) and its
      main metabolite 7-hydroxymethotrexate (7-OHMTX) and compared to the
      immunochemical fluorescence polarization immunoassay (FPIA2) determination of
      methotrexate. METHODS: Methotrexate was determined by HPLC with UV detection at
      303 nm after precipitation of proteins with trichloroacetic acid. Fluorescence
      polarization immunoassays (FPIA2) of methotrexate were performed on the TDx FLx
      Immunoassay Analyzer. RESULTS: Our data indicate good correlation between
      methotrexate levels > 1 micromol/L determined by HPLC and FPIA2. (r = 0.94,
      Spearman correlation coefficient). However, concentrations of methotrexate < 1
      micromol/L measured by fluorescence polarization immunoassay were overestimated.
      CONCLUSIONS: The concentration of MTX < 1 micromol/L are overestimated due to the
      cross reactivity with metabolites 7-OHMTX and 2,4-diamino-N10-methylpteroic acid
      (DAMPA). The cross reaction may affect the therapy and lead to relapse in
      children with acute lymphoblastic leukemia.

PMID- 21888025
TI  - C-reactive protein and complement components but not other acute-phase reactants
      discriminate between clinical subsets and organ damage in systemic lupus
      erythematosus.
AB  - BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease
      characterized by tissue injury mediated by inflammatory mechanisms. Nonetheless,
      several acute-phase proteins may remain normal or are decreased. We explore the
      association of diverse biomarkers with selected clinical features, disease
      activity, and organ damage in SLE. METHODS: One hundred and fifteen SLE patients
      were analyzed for clinical manifestations, disease activity, and organ damage.
      Serum C-reactive protein (CRP), complement C3, C4 and CH50%, alpha-1-antitrypsin
      (AAT), transferrin (Tf), procalcitonin, erythrosedimentation rate (ESR), and
      interleukin-6 were measured in patients and twenty-six healthy blood donors.
      Statistics include chi-square, Kruskal-Wallis (post hoc by Mann-Whitney) or one
      way ANOVA tests (post hoc by t tests) as appropriate. Associations were evaluated
      by the Spearman's correlation coefficient (p). RESULTS: SLE patients have lower
      C3 (85 vs. 110 mg/dL; p < 0.0001) and C4 (14.2 vs. 24.2 mg/dL; p < 0.0001) than
      controls, while CRP (4.1 vs. 1.4 mg/L; p = 0.005) and AAT (147 vs. 138 mg/dL; p =
      0.03) were higher, other biomarkers were irrelevant. Disease activity score
      positively correlated with ESR (p = 0.23, 95 % CI 0.04 to 0.4; p = 0.01) and CRP
      (p = 0.19, 0.0007 to 0.36; p = 0.04), while inverse correlations with C3 (p = 
      0.26, -0.43 to -0.08; p = 0.004), C4 (p = -0.18, -0.36 to 0.005; p = 0.04), CH50
      % (p = -0.20, -0.38 to -0.01; p = 0.02), and Tf (p = -0.35, -0.53 to -0.12; p =
      0.002) were found. According to clinical manifestations, patients with arthritis
      showed higher levels of ESR (34 vs. 20 mm/h), CRP (10 vs. 2.8 mg/L), and AAT (179
      vs. 145 mg/dL), but lower Tf (192 vs. 226 mg/dL) than those without arthritis;
      whereas active nephritis was characterized by lower serum concentrations of
      complement C3 (73 vs. 92 mg/dL), C4 (10 vs. 15 mg/dL), CH50% (80 vs. 160 U/mL)
      and Tf (196 vs. 232 mg/dL) than those patients without this manifestation. No
      other significant differences were found. CONCLUSIONS: In patients with SLE,
      acute-phase proteins behave differently depending on the kind of organ damage
      evaluated. Serum complement proteins remained as the most reliable laboratory
      markers for nephritis, while CRP was determined the best in patients with
      arthritis. The muted CRP response seen in SLE patients with active nephritis
      could have important pathogenic implications.

PMID- 21888026
TI  - Amyotrophic lateral sclerosis (ALS), a novel rare cause of elevated plasma
      troponin T levels.
AB  - In this article, we report on a patient with chronic and modestly elevated plasma
      troponin T (TnT) levels and frequent hospitalizations following the first
      admission until his death one year later. The patient was initially admitted for
      dyspnea and discharged from hospital with a diagnosis of non-ST elevation acute
      myocardial infarction (AMI). Coronary angiography and echocardiography were
      normal, but the patient received the (false) diagnosis of AMI at two further
      admissions, based purely on elevated TnT. Shortly thereafter, severe respiratory
      failure with restrictive-type spirometry pattern became the predominant clinical
      symptom, with constantly elevated TnT levels at frequent re-admissions. Due to
      inconsistent follow-up by primarily junior and non-specialist staff at a number
      of different wards, pulmonary function tests and previous smoking history were
      mis-interpreted as typical of chronic obstructive pulmonary disease (COPD). The
      patient received standard COPD treatment without any improvement. After a year of
      gradually worsening respiratory failure and repeated hospitalizations, thorough
      assessment by a pulmonologist and neurologist established the final diagnosis of
      amyotrophic lateral sclerosis (ALS). The patient died shortly thereafter. While
      progressive respiratory failure is well-known to determine morbidity and
      mortality in patients with ALS, chronically elevated TnT levels in the absence of
      coronary artery disease have, to our best knowledge, not been described so far.
      We suggest that chronic myocardial hypoxia due to ALS-related hypoxic respiratory
      failure was the most likely underlying etiology for the elevated TnT levels seen
      here but other mechanism such as immune-mediated myocardial injury cannot be
      excluded.

PMID- 21888027
TI  - Analysis of ABL kinase domain mutations conferring resistance to tyrosine kinase
      inhibitors in chronic myeloid leukemia cases from India.
AB  - BACKGROUND: The current study was undertaken to find out the frequency and
      distribution of ABL kinase domain (KD) mutations showing resistance to tyrosine
      kinase inhibitors (TKI) in CML patients from India. METHODS: A total of 24 TKI
      resistant CML patients were screened for ABL KD mutation by semi-nested reverse
      transcription PCR and sequencing. The expression of BCR-ABL transcripts was
      quantified by Real Time Taqman assay. RESULTS: Sixteen different point mutations
      were detected in 14 (58.3%) of 24 TKI resistant patients. Five out of the 16
      mutations were located at the four hot spots of ABL kinase domain: one at the P
      loop (Q252H), one at the imatinib binding site (T315I), two at the catalytic
      domain (M351, Y353F) and one at the active A loop (H396P). The three mutations,
      viz. M244V, T315I and A380V, were the most frequent mutations and accounted for
      40.9% of all resistance associated mutations. CONCLUSIONS: In the present study,
      the presence of ABL KD mutations was found to be a major cause of drug
      resistance. The T315I mutation was found to be resistant to second generation
      drugs such as dasatinib. The study reinforces the need for new therapeutic
      options which can target this mutation.

PMID- 21888028
TI  - Clinical diagnostic performance of different methods for the detection of
      antibodies to extractable nuclear antigens in connective tissue diseases: a
      cohort study.
AB  - BACKGROUND: Different methods for anti-ENA identification have been used. This
      can lead to confusion regarding the interpretation of the test results in
      clinical practice. Some studies have reported differences in sensitivity and
      specificity, but few compare clinical outcomes. Based on that, our aim was to
      compare the performance characteristics of various methods commonly used to
      detect anti-ENA antibodies in the sera of patients suspected to have connective
      tissue diseases (CTDs). METHODS: 189 patients with orders for anti-ENA were
      analyzed. Three common methods were used: DID, ELISA, and HA. Sensitivity,
      specificity, PPV, NPV, and LR were calculated using CTDs as the reference
      standard. RESULTS: 69.3% of the patients had a CTD and 32.8% had SLE. Sensitivity
      and specificity, respectively, according to the technique were: ELISA (50.0% -
      78.9%); DID (31.3% - 89.5%); HA (40.9% - 87.7%). PPV were: 88.5% (HA), 87.2%
      (DID) and 84.6% (ELISA), and NPV were: 40.5% (ELISA), 39.1% (HA) and 36.2% (DID).
      CONCLUSIONS: Based on the very similar predictive test values, we believe that,
      at least in a moderate to high pretest probability, in our methodological
      scenario, there are no significant differences in the interpretation of test
      results when using ELISA, HA, and DID for anti-ENA detection.

PMID- 21888029
TI  - Presence of murine leukemia virus (MLV)-related virus gene sequences in a
      commercial RT-PCR reagent.
AB  - BACKGROUND: The recent identification of murine leukemia virus (MLV)-related
      viruses in patients with chronic fatigue syndrome (CFS) has aroused much
      interest, not least among sufferers. However, other studies failed to detect
      these viruses in CFS patients. METHODS: We wanted to establish a MLV-related
      virus real-time PCR for routine diagnostics. RESULTS: Our study identified false
      positive MLV-related virus results due to a contamination of Superscript III
      Platinum One-Step Quantitative RT-PCR System (Invitrogen). CONCLUSIONS: This
      observation may be helpful to elucidate discrepant results for the detection of
      MLV-related virus like xenotropic MLV-related virus (XMRV) in recently published
      studies.

PMID- 21888030
TI  - Laboratory reference values of complete blood count for apparently healthy adults
      in Ethiopia.
AB  - BACKGROUND: The objective of this study was to evaluate reference intervals for
      complete blood cell count parameters among apparently healthy 1,807 adults from
      Addis Ababa, Ethiopia. METHODS: Blood specimens were collected from each
      participant using standard procedures. The collected aliquots were processed
      according to standard operating procedures to determine participants' complete
      blood counts. Non-parametric methods were employed to calculate the reference
      intervals and 90% confidence intervals for complete blood counts. RESULTS:
      Overall the results show that reference ranges for women are lower than men. The
      white blood cell count, neutrophil, lymphocyte, monocyte, eosinophil, and
      basophil reference values appear to be lower than values reported elsewhere.
      CONCLUSIONS: Our study is the first comprehensive study on reference intervals of
      complete blood count among apparently healthy adults in Ethiopia. Future studies
      that assess other hematological parameters and studies that assess reference
      values for African pediatric populations are warranted.

PMID- 21888031
TI  - Isolation of Cupriavidus metallidurans from razor blade during paraffin embedded
      tissue sectioning.

PMID- 21888032
TI  - Diallyl disulphide and lovastatin: effects on energy and protein utilisation in,
      as well as methane emission from, sheep.
AB  - Currently research on feed supplementation with natural compounds to improve
      energy and protein utilisation and to mitigate the greenhouse gas methane in
      ruminants is intensively pursued. Two compounds, diallyl disulphide (DADS), an
      important component of garlic oil, and lovastatin, an inhibitor of a key enzyme
      of methanogenic Archaea, were selected on the basis of their in vitro anti
      methanogenic potential. In three 23-day experimental runs, six sheep received hay
      and concentrate in a duplicate 3 x 3 Latin square design. The concentrate was
      either not supplemented or supplemented with either 4 g DADS or 80 mg lovastatin
      per kg of total dietary dry matter. There were no refusals of concentrate for any
      treatment. Respiratory measurements were conducted on experimental days 7/8
      (Period 1) and days 17/18 (Period 2). Relative to the control, digestibility of
      neutral detergent fibre (NDF) tended to increase (p = 0.09) with DADS by 14%.
      This was associated with an increased (p = 0.07) body energy retention of the
      animals. Effects on nitrogen balance and ruminal fermentation traits were never
      significant. No influence of supplements or period was found on total daily CH4
      production which averaged at 28.6 g per sheep. However, across both periods the
      amount of CH4 produced per kg NDF digested was lower (-8%; p = 0.02) with DADS
      than without supplementation, and the lovastatin treatment ranged in between. In
      conclusion, the study demonstrated a certain potential of DADS to improve fibre
      digestion and body energy retention and to limit CH4 formation in relation to
      digestible fibre intake, while lovastatin remained ineffective.

PMID- 21888033
TI  - Evaluation of complementary effects of 9,10-anthraquinone and fumaric acid on
      methanogenesis and ruminal fermentation in vitro.
AB  - The objective of the present study was to investigate the hypothesis that 9,10
      anthraquinone (AQ) in combination with fumaric acid (FMA) may provide
      complementary effects to inhibit methanogens and enhance rumen's capacity for
      better utilisation of FMA towards propionate production. Three levels of AQ and
      four levels of FMA were tested in a 3 x 4 factorial design using in vitro gas
      production technique. AQ reduced the total gas and methane production
      significantly. The combination of 4 ppm AQ with FMA had additive effect on
      concentration of propionate. Supplementation of AQ alone resulted in hydrogen
      accumulation (p < 0.001), whereas presence of FMA (up to 6.5 mM) along with AQ
      declined hydrogen concentration (p < 0.001). The level of 4 ppm AQ did not affect
      in vitro digestibility, however, a reduction of organic matter digestibility was
      caused by 8 ppm AQ (p < 0.001), which was partially compensated by the addition
      of FMA (p = 0.06). The optimum FMA level depended on the AQ concentration. At 4
      ppm AQ, a FMA level of 3.5 mM had best possible effect on partitioning factor and
      microbial biomass production (p < 0.001), though, at 8 ppm AQ the higher level of
      FMA (6.5 mM) responded better. Overall, FMA in combination with AQ provided an
      alternative hydrogen sink and might be introduced as a novel strategy for
      mitigation of enteric methane emission. Nevertheless, the result should be proved
      by in vivo experiments.

PMID- 21888034
TI  - Nitrogen excretion of adult sheep fed silages made of a mixed sward or of pure
      unfertilised grass alone and in combination with barley.
AB  - Four adult rumen-fistulated wether sheep were fed silages combined with barley.
      The silages consisted of 48% grasses, 28% legumes and 24% other forbs (GCF) or of
      pure grass (G). The swards received no mineral fertiliser. The dry matter (DM)
      and fibre contents were lower in GCF than in G. Crude protein content of DM in
      GCF and G were 145 g/kg and 102 g/kg respectively. DM content as ash, lipids and
      non-fibrous carbohydrates were rather similar in both silages. About 40g DM were
      offered per kg BW0.75 and day either as silage alone or as a mixture of silage
      and barley (60:40). Faecal N excretion was greater with GCF than with G. The
      proportion of faecal bacterial and endogenous debris N reached 75 and 73% when
      GCF or G was fed, respectively. Undigested dietary N represented about 20%, and
      water soluble N accounted for 5-6% of faecal N. GCF caused more urinary N than G.
      Barley reduced urinary N excretion when supplemented to GCF. No dietary influence
      on urinary non-urea nitrogenous compounds was shown. GCF caused higher urinary
      urea N excretion than G and barley reduced this fraction when replacing part of
      GCF. Based on the urinary urea N proportions, it is concluded that N intake
      exceeded N requirement for any of the four diets fed. Dietary supplementation of
      ruminally fermentable carbohydrates can reduce urinary N excretion and this
      improves the efficiency of utilisation of N in N-unfertilised biodiverse
      grassland/ruminant farming systems.

PMID- 21888035
TI  - Effects of keratinase supplementation of corn-soybean meal based diets on
      apparent ileal amino acid digestibility in growing pigs and serum amino acids,
      cytokines, immunoglobulin levels and loin muscle area in nursery pigs.
AB  - Two experiments were conducted to evaluate effects of keratinase for growing and
      nursery pigs. In Exp. 1, six pigs (32.3 +/- 2.8 kg body weight), fitted with a
      simple T-cannula at the distal ileum, were assigned to one of two 3 x 3 Latin
      squares involving three periods and three diets including a basal diet and the
      same diets supplemented with 0, 0.05 or 0.1% keratinase. Dietary keratinase
      supplementation increased the apparent ileal digestibility of crude protein (CP),
      arginine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine,
      threonine, tryptophan, alanine, glutamic acid and proline (p < 0.05).
      Digestibility coefficients did not differ between pigs fed 0.05 and 0.1%
      keratinase. In Exp. 2, 24 piglets weaned at 30 +/- 2 d of age were used in a 2 x
      2 factorial design experiment with two CP concentrations (19 vs. 22%) and two
      levels of keratinase supplementation (0 vs. 0.05%). Keratinase supplementation
      increased (p < 0.05) average daily gain, serum arginine concentration and loin
      muscle area but decreased (p < 0.05) serum interleukin-10 concentrations. The
      reduction in dietary CP level decreased (p < 0.05) serum urea nitrogen
      concentrations, isoleucine, serine and proline concentrations, but increased
      serum arginine concentrations. Few interactions between keratinase
      supplementation and dietary CP concentration were observed. This study indicated
      that dietary keratinase supplementation improved apparent ileal amino acid
      digestibility for growing pigs and had a positive effect on weight gain, immune
      response and loin muscle area for nursery pigs.

PMID- 21888036
TI  - Determination of energy and amino acid digestibility in growing pigs fed corn
      distillers' dried grains with solubles containing different lipid levels.
AB  - Two experiments were conducted to estimate the digestibility of energy, nitrogen
      and amino acids (AA) in growing pigs fed diets containing one of five corn
      distillers' dried grains with solubles (DDGS), including three normal oil DDGS
      (NO-DDGS) and two low oil DDGS (LO-DDGS) samples. Exp. 1 was conducted to
      determine the digestible energy (DE) and metabolisable energy (ME) content. Six
      growing barrows (initial body weight [BW]: 35.1 +/- 2.2 kg) were allotted to a 6
      x 6 Latin square design, with six periods and six diets. One diet was a corn
      soybean meal basal diet and the other five diets were based on corn, soybean meal
      and 28.8% DDGS. The average DE and ME values for the three NO-DDGS samples were
      16.0 and 14.9 MJ/kg dry matter (DM). These values were 9 and 13% greater than the
      LO-DDGS values of 14.7 and 13.2 MJ/kg DM respectively. Exp. 2 was conducted to
      determine and compare apparent (AID) and standardised (SID) ileal digestibility
      for crude protein and AA in the five DDGS samples. Six growing barrows (initial
      BW, 32.2 +/- 1.9 kg) fitted with a simple T-cannula were allotted to a 6 x 6
      Latin square design with six periods and six diets. Five of the diets were based
      on the five DDGS samples, and the remaining one diet was nitrogen-free diet based
      on cornstarch and sucrose. Titanium dioxide (0.1%) was used as inert marker. The
      results of the experiment showed the largest variation among the different
      samples in AID and SID for lysine (from 41.8 to 65.8% and 53.8 to 73.9%
      respectively) and threonine (from 54.3 to 73.8% and 65.2 to 79.5% respectively).
      Also, among the indispensable AA, the SID values for arginine, histidine,
      threonine and tryptophan observed in LO-DDGS were not different from the values
      derived from NO-DDGS. In conclusion, LO-DDGS may have decreased energy compared
      with NO-DDGS because of its lower fat content. However, oil removal during the
      production of DDGS may not affect amino acid digestibility.

PMID- 21888037
TI  - Bioavailability of two organic forms of zinc in comparison to zinc sulphate for
      weaning pigs fed a diet composed mainly of wheat, barley and soybean meal.
AB  - This study was performed to compare the bioavailability of two organic zinc
      compounds, a zinc glycinate complex and a zinc amino acid chelate with that of
      zinc sulphate in growing pigs fed a basal diet composed mainly of wheat, barley
      and soybean meal. The experiment included 96 pigs with an average body weight of
      8 kg, allotted to ten groups of nine to ten pigs each. The first group received
      the basal diet, containing 42 mg of native zinc per kg, without zinc
      supplementation over a period of five weeks. The other nine groups received the
      basal diet supplemented with 15, 30 or 50 mg of zinc/kg as zinc sulphate, zinc
      glycinate or the zinc amino acid chelate. Pigs fed the unsupplemented diet had a
      lower growth performance (body weight gain, feed conversion ratio) than the other
      nine groups. Supplementation of 15 mg zinc/kg diet (irrespective of zinc form)
      was sufficient to yield optimum growth performance. Plasma zinc concentration and
      activity of alkaline phosphatase were rising with increasing zinc supplementation
      levels up to a maximum reached at a supplementary level of 30 or 50 mg/kg diet
      for activity of alkaline phosphatase and plasma zinc concentration, respectively.
      The response of those parameters to zinc supplementation did, however, not differ
      between the three zinc compounds considered. The apparent digestibility of zinc
      from the diet was also not different for the three zinc compounds. In conclusion,
      these findings show that the bioavailability of the two organic zinc compounds
      did not differ from that of zinc sulphate in growing pigs fed a diet with wheat,
      barley and soybean meal as major components.

PMID- 21888038
TI  - Effects of dietary lipids and Clostridium butyricum on the performance and the
      digestive tract of broiler chickens.
AB  - The effects of two sources of dietary lipids and supplementation of Clostridium
      butyricum on performance and intestinal metabolism of broilers were investigated.
      In a 2 x 2 factorial arrangement, 168 one-day-old broiler chicks were divided
      into four treatment groups, and fed four diets with two lipid sources (soya bean
      oil or fish oil, at 25 g/kg and 30 g/kg in starter and grower diets
      respectively), and without or with supplementation of C. butyricum (1 x 10(9)
      colony forming units per kg diet). C. butyricum had no effect on broiler
      performance. At 20 and 40 d of age, the pH of caecal digesta and the relative
      length of caecum were decreased after supplementation of C. butyricum (p < 0.05).
      After this treatment, the activity of alkaline phosphatase was increased in
      jejunal mucosa at 40 d of age (p < 0.01). Furthermore, there were increases in
      populations of lactic acid bacteria and the concentrations of acetic acid, n
      butyric acid, n-valeric acid and total short chain fatty acids in caecal digesta
      of birds fed C. butyricum (p < 0.05). A significant interaction between lipid
      source and C. butyricum was found in the pH of caecal digesta at 20 d of age (p <
      0.01). The results of the present study indicated that dietary supplementation of
      C. butyricum maybe a benefit for gut health of broiler chickens.

PMID- 21888039
TI  - Take home lead exposure in children of oil field workers.
AB  - Childhood lead poisoning is a major, preventable environmental health problem.
      While residential lead-based paint and lead contaminated dust and soil are the
      most common sources of childhood lead poisoning, children can also be at risk if
      they live with an adult with a job or hobby that involves exposure to lead.
      Currently, the Oklahoma Childhood Lead Poisoning Prevention Program (OCLPPP) has
      a small number of cases of "take home" lead exposure in children of oil field
      workers. These workers may come in contact with a threading compound, "pipe dope"
      that can contain large amounts of lead. Workers handling this product may be
      exposed to lead by not following safety instructions. Additionally workers may
      not be provided the facilities to shower and change out of the contaminated
      clothing before leaving the work location. The OCLPPP recommends employers and
      worksites should consider effective alternative options like lead free
      biodegradable pipe dopes or dope free connections to prevent workers and their
      families from adverse health effects associated with lead.

PMID- 21888040
TI  - The University of Oklahoma College of Medicine summer medical program for high
      school students.
AB  - To enhance diversity of applicants to University of Oklahoma College of Medicine,
      a Summer Medical Program for High School Students was started in 2009. This
      comprehensive pipeline program included sessions on applying to medical school,
      interaction with a panel of minority physicians and health care professionals
      role models, clinically oriented didactics taught by physician faculty, shadowing
      experiences in clinics and hospitals, and presentation of student research
      reports. Students' assessments in 2009 showed increased understanding of the
      medical school application process, the medical curriculum and the medical field,
      and an increase in students'likeliness to choose a medical career. Importance of
      long-term mentoring and follow-up with students to sustain their medical
      interests is discussed.

PMID- 21888041
TI  - Do intra-articular (IA) steroid injections relieve pain and improve outcomes
      beyond two weeks for patients with osteoarthritis (OA) of the knee.

PMID- 21888042
TI  - Planned recruitment of the Med Center medical staff to the OSMA.

PMID- 21888043
TI  - [Current status of genome research on open-angle glaucoma in Finland].
AB  - Loss of vision and visual impairment due to glaucoma can be prevented or delayed,
      if the disease is detected at an early stage. The most important risk factors for
      open-angle glaucoma include age, elevated intraocular pressure, exfoliation of
      the lens, i.e. exfoliation syndrome, and genetic factors. To date, genetic
      studies on glaucoma have revealed more than 20 gene loci and three candidate
      genes, myocilin (MYOC), optineurin (OPTN) and WD repeat domain 36 (WDR36). A
      mutation in both the MYOC and WDR36 genes has been found in Finnish families.

PMID- 21888044
TI  - [The significance of attention-deficit hyperactivity disorder for the future of
      the child and the young].
AB  - Attention-deficit hyperactivity disorder (ADHD) in not necessarily a phenomenon
      passing away with childhood, instead in some patients attention problems
      continue, causing disturbances until adulthood. ADHD hampers studying and getting
      along in working life, social relationships as well as traffic skills. ADHD is
      also associated with increased risk of substance abuse and criminal behavior.
      Several studies have shown that stimulant medication and psychosocial forms of
      treatment are able to reduce long-term handicaps of ADHD and associated
      psychiatric morbidity.

PMID- 21888045
TI  - [Leucopenia in children].
AB  - Decreased leukocyte values in children are usually due to the decrease in the
      number of neutrophilic granulocytes. This is usually a transient phenomenon
      associated with viral infections. In infancy and early childhood, immune mediated
      neutropenias are possible causes of prolonged leukopenia. Causes of rare
      leukopenias are numerous, including underlying diseases such as congenital
      myelopathy, a syndrome or malignant hematological disease. The risk of infection
      associated with neutropenia is increased especially in patients with a production
      defect of the bone marrow as the underlying cause.

PMID- 21888046
TI  - [Infection control in the intensive care unit].
AB  - The basis of infection control is systematic monitoring of infections in the
      patient care units, whereby a clear-cut basis for focusing of the control is
      obtained. An entity of several distinct evidence-based methods, i.e. treatment
      bundle, is increasingly utilized. Though difficult in practice, the goal is zero
      tolerance, whereby all infections during the treatment should be prevented.
      Central principles of infection control include use of antimicrobial hand rinse
      in all patient care, appropriate use of protective devices and contact isolation
      as required by the detected microorganisms.

PMID- 21888047
TI  - [IOSCA - Infantile onset spinocerebellar ataxia].
AB  - IOSCA is a difficult, progressive degenerative disease causing damage to the
      peripheral and central nervous system. All known 24 patients are Finnish. Initial
      symptoms include ataxia, athetosis, ophthalmoplegia, hearing disability and
      muscular hypotonia. Sensory axonal neuropathy and associated optic atrophy are
      typical of the disease, as well as primary hypergonadotropic hypogonadism in
      girls. The patients are progressively severely disabled from the age of approx.
      eighteen months. The pathogenesis is unknown and there is no curative treatment
      for the disease.

PMID- 21888048
TI  - [How and when is topical treatment applied into the ear?].
AB  - Topical treatment is the first-line treatment for inflammation of the external
      auditory canal and chronic otitis media, without the need of systemic
      antimicrobial drug therapy. The ear canal is cleaned mechanically, by rinsing
      with saline, and finally dried by suction. A bacterial or fungal culture specimen
      should be taken, if the inflammation does not heal with the first treatment or
      recurs rapidly. High local drug levels without systemic adverse effects are
      achieved with ear drops. A combinatorial broad-spectrum antibiotic/corticosteroid
      ear drop is the most effective remedy for bacterial inflammation, whereas the
      most important therapeutic procedure in fungal infections is cleaning and topical
      medication.

PMID- 21888049
TI  - [An unusual etiology for pain in the back, hip and leg in a young woman].
AB  - We present a 28-year old woman, suffering from low back and right leg pain for 5
      years, with motor and sensory deficits of the leg. Disc herniation, hip related
      pain, depression, and even an osteoid osteoma were suspected during the years,
      and several imaging studies had been undertaken. Based on an ENMG-study a lesion
      affecting the right L5-nerve root distal to the ganglion was suspected. On a
      pelvic MRI a nonenhancing tumor of the right L5-root was seen. The tumor was
      resected operatively. On histologic examination an uncommon granulocellular tumor
      was diagnosed. The patient recovered almost completely.

PMID- 21888050
TI  - [Update on current care guidelines: Hip fracture].
AB  - In Finland approximately 7,000 hip fractures occurred annually during 1996-2008.
      Risk of hip fracture can be diminished through efforts to prevent falls and
      osteoporosis. A hip fracture is treated operatively, with the aim of early
      mobilisation and full weight bearing. Postoperative care and rehabilitation
      requires multidisciplinary and multifaceted management, focusing on improvement
      of the patient's physical condition, appropriate pain management, the prevention
      of delirium and other possible complications. Rehabilitation should be
      centralised in specialised rehabilitation centres for the elderly. Secondary
      prevention of future fractures should include management of osteoporosis and fall
      prevention.

PMID- 21888051
TI  - [Molecular mechanisms of circadian clock functioning].
AB  - Most physiological processes of all organisms are rhythmic with a period of about
      24 h and are generated by an endogenous biological CLOCK present in all cells.
      However, there is also a central CLOCK--the primary circadian pacemaker which is
      localized in the suprachiasmatic nuclei of the mammalian hypothalamus. Factors of
      groups Period (PER1, PER2 and PER3), BMAL (BMAL1 and BMAL2), CRYptochromes (CRY1
      and CRY2) as well as some other factors are the components of this circadian
      CLOCK system. Some of these genes contain E-box sequences and their expression is
      regulated by a transcription factor complex CLOCK-BMAL1. The enzymes responsible
      for the post-translational modification of circadian gene products are also the
      components of circadian CLOCK system. These enzymes define CLOCK's work and
      determine the duration of circadian biorhythm and functional state of the whole
      organism. The most important of these enzymes are casein kinase-1epsilon and 
      1delta. We have analysed data about the interconnection between the circadian
      CLOCK system, cell cycle, and cancerogenesis as well as about the sensitivity of
      circadian gene expression to the action of toxic agents and nanomaterials.

PMID- 21888052
TI  - [Coordinative compounds of zinc with N-substituted thiocarbamoyl-N'
      pentamethylensulfenamides--activity modifiers of enzymes of proteolytic and
      glycolytic action].
AB  - The influence of a number of coordinative compounds of zinc with N-substituted
      thiocarbamoil-N'-pentamethylensulfenamides on activity of elastase, alpha-L
      rhamnosidase and alpha-galactosidases evidence for a possibility of their usage
      as stimulators or inhibitors of enzymes tested have been studied. It was shown
      that all the compounds in concentration of 0.1 and 0.01% inhibited by 90-100%
      Bacillus thuringiensis 27-88Els+ elastase activity. [Zn(L2)Br2], [Zn(L1)(NCS)2]
      and [Zn(L3)(NCS)2] at 20 h exposition activated Cryptococcus albidus 1001 alpha-L
      rhamnosidase activity. The rest of compounds influenced it on the control level
      or inhibited it by 7-23%. The obtained results testify that essential role is not
      played by separate fragments (L-ligand and anions), but by molecules of zinc
      complexes as a whole. All the studied complexes, exept for [Zn(L3)(NCS)2],
      induced alpha-L-rhamnosidase activity of Eupenicillium erubescens 248 (7 to 60%).
      All zinc compounds (concentration 0.01%, exposition time - 60 min) influenced at
      the control level Aspergillus niger and Cladosporium cladosporioides alpha
      galactosidases activity, however inhibited (up to 20%) activity of Penicillium
      canescens alpha-galactosidase. The increasing of exposition time of the compounds
      tested with enzymes up to 20 h testify to selective action of separate compounds
      on enzymes tested. The data obtained prove, that the character of interaction of
      zinc complexes is changed depending on the enzyme tested and its strain-producer.

PMID- 21888053
TI  - [The influence of ATP-dependent K(+)-channel diazoxide opener on the opening of
      mitochondrial permeability transition pore in rat liver mitochondria].
AB  - The influence of mitochondrial ATP-dependent K(+)-channel (K+(ATP)-channel)
      opener, diazoxide (DZ) on the mitochondrial permeability transition pore (MPTP)
      opening in rat liver mitochondria is studied. In the absence of DZ the MPTP
      opening leads to the increase in the rate of K(+)- and Ca(2+)-cycling supported
      by the simultaneous functioning of K(+)-channels and K+/H(+)-antiporter, and also
      Ca(2+)-uniporter together with MPTP as the cations influx and efflux pathways.
      Independent of MPTP opening, the activation of both constitutes of K(+)-cycle,
      K(+)-uptake as well as K+/H(+)-exchange, by DZ is observed. It is shown that the
      activation of transmembrane exchange of K+, combined with MPTP opening, results
      in partial inhibition of the latter. A simple methodical approach for the
      estimation of DZ influence on the open state of mitochondrial pore is proposed.
      It is shown that MPTP closure followed by Ca2+ reentry to the matrix is
      accompanied by the K+/H(+)-exchange inhibition which takes place in the same
      timeframes as the increase in matrix Ca2+ content. Relevant to physiological
      conditions, an important physiological function of MPTP is revealed, that is the
      maintenance of relatively low matrix level of Ca2+ accompanied by the
      acceleration of transmembrane ion exchange (K+ and Ca2+) which could strongly
      influence the energy state and energy-dependent processes in mitochondria.

PMID- 21888054
TI  - [Regulation of the mitochondrial ATP-sensitive potassium channel in rat uterus
      cells by ROS].
AB  - In previous study we demonstrated the presence of ATP-sensitive potassium current
      in the inner mitochondrial membrane, which was sensitive to diazoxide and
      glybenclamide, in mitochondria isolated from the rat uterus. This current was
      supposed to be operated by mitochondrial ATP-sensitive potassium channel
      (mitoK(ATP)). Regulation of the mitoK(ATP) in uterus cells is not studied well
      enough yet. It is well known that the reactive oxygen species (ROS) can play a
      dual role. They can damage cells in high concentrations, but they can also act as
      messengers in cellular signaling, mediating survival of cells under stress
      conditions. ROS are known to activate mitoK(ATP) during the oxidative stress in
      the brain and heart, conferring the protection of cells. The present study
      examined whether ROS mediate the mitoK(ATP) activation in myometrium cells.
      Oxidative stress was induced by rotenone. ROS generation was measured by 2',7'
      dichlorofluorescin diacetate. The massive induction of ROS production was
      demonstrated in the presence of rotenone. Hyperpolarization of the mitochondrial
      membrane was also detected with the use of the potential-sensitive dye DiOC6
      (3,3'-dihexyloxacarbocyanine iodide). Diazoxide, a selective activator of
      mitoK(ATP), depolarized mitochondrial membrane either under oxidative stress or
      under normal conditions, while mitoK(ATP) blocker glybenclamide effectively
      restored mitochondrial potential in rat myocytes. Estimated <K1/2> value for
      diazoxide to mitoK(ATP) under normoxia was four times higher than under oxidative
      stress conditions: 5.01 +/- 1.47-10(-6) M and 1.24 +/- 0.21 x 10(-6) M
      respectively. The ROS scavenger N-acetylcysteine (NAC) successfully eliminates
      depolarization of mitochondrial membrane by diazoxide under oxidative stress.
      These results suggest that elimination of ROS by NAC prevents the activation of
      mitoK(ATP) under oxidative stress. Taking into account the higher affinity of
      diazoxide to mitoK(ATP) under stress conditions than under normoxia, we conclude
      that the oxidative stress conditions are more favourable than normoxia for the
      activation of mitoK(ATP). Thus we hypothesize that the ROS regulate the activity
      of the mitoK(ATP) in myocytes.

PMID- 21888056
TI  - [Peculiarities of secondary structure of serum albumin of some representatives of
      the animal kingdom].
AB  - Methods of infrared (IR) spectroscopy and circular dichroism (CD) are suitable
      techniques for detection of proteins structural changes. These methods were used
      for determinating peculiarities of the secondary structure of serum albumins in
      some representatives of two classes of reptiles: Horsfield's tortoise (Testudo
      horsfieldi), water snake (Natrix tessellata) and grass snake (Natrix natrix) and
      birds: domestic goose (Anser anser), domestic chicken (Gallus domesticus),
      domestic duck (Anas platyrhyncha) and dove colored (Columba livia). An analysis
      of IR spectra and spectra obtained by the method of CD of serum albumins of both
      classes representatives revealed that beta-folding structure and alpha-helical
      sections that form the alpha-conformation play an important role in
      conformational structure formation of polypeptide chain and also disordered sites
      of molecules of these proteins. It was observed that certain redistribution
      depending on animals species exists, in the formation of secondary structure of
      serum albumins of the investigated representatives of reptiles and birds classes
      between the content of beta-folding structure, alpha-helical sections and
      disordered sites in molecules of these proteins.

PMID- 21888055
TI  - [Advantages of two- or polyvalent binding of a receptor to the corresponding
      ligand in comparison to univalent binding].
AB  - The features of monovalent and bivalent binding of receptors (or antibodies) with
      a polyvalent ligand (or with an antigen) are considered. It is shown that the
      rigid connection of the binding sites of the receptor brings to high increase of
      binding affinity for the corresponding ligand, but only in case if its epitopes
      are fully complementary to both sites of the receptor binding. If not, then there
      is no advantage of the binding of bivalent receptor before univalent binding. If
      the binding sites of the receptor are connected by a flexible linker, then
      regardless of location of epitopes of the corresponding ligand there is the
      successful fastening of receptor and ligand. Exactly the connection by a flexible
      linker is used by Nature in most cases at constructing of polyvalent receptors.

PMID- 21888057
TI  - [Influence of antitumor system rhenium-platinum on biochemical state of the
      liver].
AB  - Influence of the antitumour rhenium-platinum system on biochemical liver
      characteristics in the model of tumor growth (Guerin carcinoma) was studied and
      possible hepatoprotective activity of rhenium cluster compounds when introducing
      them in different forms was shown, that was confirmed by decreasing of diagnostic
      enzymes activity in blood (aminotransferase--AST 6 times and ALT 5.6 times,
      lactatedehydrogenase 4.9 times, gamma-glutamyltranspeptidase 3.6 times) and
      normalization of morphological state of the liver cells. The hepatoprotective
      activity of the cluster rhenium compound with adamanthyl ligands was confirmed in
      the model of acute toxic hepatitis. Introduction of this compound led to
      reduction of the concentration of MDA in homogenates of liver tissue (2 times),
      and in blood plasma (3.8 times); to reduction of levels of diagnostic liver
      enzymes in blood--AST and ALT 5.8 and 5.5 times respectively in comparison with
      control group. Some aspects of the mechanism of hepatoprotection were discussed,
      that included the presence of conjugated systems around the quadrupol rhenium
      rhenium bond and alkyl radicals with significant positive inductive effects.

PMID- 21888058
TI  - [Tissue specificity of lipid peroxidation under emotional stress in rats].
AB  - The intensity of lipid peroxidation and activity of antioxidant system enzymes in
      the blood plasma, brain and cardial muscle of laboratory rats under 40 days of
      isolation and violation of diurnal cycle was studied. The obtained data show that
      on the background of concentration changes in NO changes also take place in the
      intensity of lipid peroxidation process, indicated by changes in the
      concentration of TBA-active products and diene conjugates. The changes taking
      place in the activity of superoxidedismutase, catalase, succinatdehydrogenase,
      creatine kinase and aldolase under stress were studied. The resulting data show
      that isolation of animals and violation of diurnal cycle are the factors causing
      a significant reduction in the energy metabolism in the brain and heart tissue
      cells and resulting in oxidative stress that, in its turn, may become the reason
      for development of toxic radicals. Furthermore, prolonged stress may result in
      irreversible processes that are considered to be the reasons for significant
      pathologies of the cardiovascular system.

PMID- 21888059
TI  - [Intensity of peroxidation processes and activity of antioxidant enzymes in rat
      tissues at high chromium level in the diet].
AB  - The data on the influence of chromium in different tissues of rats at its
      consumption with mixed fodder in the form of CrCl3 x 6H2O on the intensity of
      peroxidation processes and activity of antioxidant enzymes are presented. The
      degree of high chromium content in the studied tissues of rats at its addition to
      mixed fodder in the amount of 200 microg/kg during 30 days was established.
      Chromium content in the rat tissues decreased in the order: the spleen, heart,
      kidneys, lungs, brain, liver, skeletal muscle. In all tissues of rats fed with
      mixed fodder with chromium addition, except for skeletal muscles, content of
      lipid peroxidation products--hydroperoxide and TBARS-products decreased. The
      content of lipid peroxidation products decreased in the spleen, kidneys, liver
      and lungs. Also in all organs and tissues of rats the activity of glutathione
      peroxidase, glutathione reductase and catalase increased at the action of
      chromium. In the brain and kidneys the level of reduced glutathione increased.
      Superoxide dismutase activity was significantly higher not only in the heart and
      skeletal muscles of animals and is probably equal in the lungs and liver, and in
      other organs--the brain, kidneys and spleen in animals of the studied group the
      enzyme activity was lower as compared to animals of the control group. Obtained
      results demonstrate the regulatory influence of chromium on free radical process
      in the rat tissues.

PMID- 21888060
TI  - [Comparative investigation by spectrofluorimetry and flow cytometry of plasma and
      inner mitochondrial membranes polarisation in smooth muscle cell using potential
      sensitive probe DiOC6(3)].
AB  - Possibility of the use of flow cytometry and spectrofluorimetry analysis for
      investigation mitochondria and plasma membrane polarization in myometrium cell
      suspension using potential-sensitive probe 3,3'-dihexyloxacarbocyanine [DiOC6(3)]
      has been demonstrated. The obtained results confirm the use of DiOC6(3) for
      studying the influence of effectors on transmembrane potentials of intact cell
      compartments.

PMID- 21888061
TI  - [The simplest molecular model of 2'-deoxyribopolinucleotides sugar-phosphate
      backbone: quantum-chemical adequacy check].
AB  - The physical adequacy of the simplest molecular model "sugar residue (SR)-
      phosphate group (PG)--SR" of 2'-deoxyribopolinucleotides sugar-phosphate backbone
      is confirmed at DFT B3LYP/6-31++G(d,p) and DFT B3LYP/6-31G(d,p) of quantum
      chemical methods. It is proved that complicacy of the model to the "SR-PG-SR-PG
      SR" and higher levels does not noticeably change the numerical values of torsion
      angles. Also these angles depend negligibly on counterion nature (e.g. Na+ to
      Li+, K+ or Cs+ change) and transition from vacuum to continuum approximation with
      medium dielectrical values of 1.4, 24.9, and 78.4. It is shown that model loses
      its adequacy when PG is the end link.

PMID- 21888062
TI  - [Investigation of metabolism of high-molecular phosphorus-containing compounds of
      the nervous system at the Palladin Institute of Biochemistry of National Academy
      of Sciences of Ukraine (1951-1965)].

PMID- 21888063
TI  - [Advances in preservative-free glaucoma drops].
AB  - Ophthalmic solutions are the main therapeutic methods used in the treatment of
      ocular diseases, including glaucoma. Preservatives are added in multidose
      solutions to reduce the risk of microbial contamination. Repeated use of topical
      medication, especially in patients treated for glaucoma, has many adverse effects
      especially on the ocular surface. This paper provides an overview of the role of
      preservatives in antiglaucoma preparations, and their impact on the ocular
      surface.

PMID- 21888064
TI  - [Alternative treatments in glaucoma, independent from ocular pressure].
AB  - Glaucoma is a medical condition that affects the optic nerve of the eye and can
      lead to a permanent loss of vision if left untreated. It is now clear that IOP
      (intraocular pression) lowering treatment may significantly delay or prevent
      glaucoma development and progression. Although current ocular hypotensive therapy
      is generally considered safe, alternative treatments may also be considered to
      slow the progression and prevent the development of complications of the disease.

PMID- 21888065
TI  - [Etiology of central retinal vein occlusion].
AB  - Arteriosclerosis is responsible for the majority of primitive pictures of central
      retinal vein occlusion occurrence. The venous occlusions appearing during the
      development of the already known disorders represent secondary venous occlusions.
      In young adults central retinal vein occlusion probably represents a general
      nonspecific change emerging from a number of individual causes or maybe a
      combination of causes e.g. multifactorial etiology. During unusual cases of
      central retinal vein occlusion the etiology is known but within the vast majority
      of patients the specific cause or even the causes that contribute the occurrence
      of this disease remain unknown since the ophthalmic literature is limited by a
      scarcity of histopathologic material.

PMID- 21888066
TI  - [Risk factors in central retinal vein occlusion].
AB  - Risk factors for the occurrence of central retinal vein occlusion are to a
      certain extent similar to those of cardiovascular diseases (e.g.
      arteriosclerosis, arterial systemic hypertension, diabetes mellitus,
      dislipidemia). Hyperhomocysteinemia is an essential risk factor for
      arteriosclerosis intervening also directly in the local mechanism of causing
      venous and arterial occlusions. Ocular hypertension and glaucoma are risk factors
      significantly associated with pathogenesis of central retinal vein occlusion.
      Therapy with anticoagulants and platelet anti-aggregating agents exposes the
      patient to developing central retinal vein occlusion influencing also adversely
      the visual outcome without having any evidence of protective or beneficial
      effect.

PMID- 21888067
TI  - [Chronic spontaneous retinal detachment].

PMID- 21888068
TI  - [Glaucoma County Center].
AB  - Sunday 10 April it was opened in Braila Regional Centre of Glaucoma. It was
      located in the hospital in a new and modern space. The Braila Regional Glaucoma
      Centre will desire to monitoring and excellent diagnosis in Glaucoma.

PMID- 21888069
TI  - [Posttraumatic hyphema with secondary glaucoma].
AB  - The authors present in detail (symptoms, signs, predisposing factors,
      complications, treatment) one of the most common signs seen in the eyeball
      contusion--traumatic hiphema. There are presented concepts for proper treatment
      of hiphema with secondary glaucoma and for relapsing hiphema.

PMID- 21888070
TI  - [Therapeutic approach in patients with age-related macular degeneration and
      cataract].
AB  - Management of the patient with coexisting cataract and AMD presents unique
      challenges to the cataract surgeon, the retina specialist, and the patient. A
      common clinical scenario is the patient in whom both the cataract and macular
      pathology appear to be contributing to decreased visual acuity. As with any
      surgery, the expectations from cataract removal must be evaluated thoroughly and
      understood clearly by both the patient and the cataract surgeon. Most patients
      with AMD who undergo cataract surgery feel that the surgery is worthwhile, and
      they report improvement of visual function and quality of life. In patients with
      mild AMD, improvement in central visual acuity and attainment of driving vision
      are realistic and achievable goals. In an eye with central disciform scarring or
      geographic atrophy there may be potential for improvement in color
      discrimination, contrast, or clarity of peripheral vision. In cases of dense
      cataract obscuring macular detail, cataract removal may be necessary to allow for
      adequate biomicroscopy and angiography, especially in an eye that may be at high
      risk for the development of choroidal neovascularization. It is often challenging
      to estimate the relative impact on visual impairment made by the lens opacities
      and the macular changes and the benefits and risks of cataract surgery in eyes
      with AMD should be carefully evaluated. Is cataract surgery justified in these
      patients? Does cataract surgery aggravate AMD in some patients?

PMID- 21888071
TI  - [Correlations of fluorescein angiography and optical coherence tomography (OCT)
      in the diagnosis of age-related macular degeneration].
AB  - Diagnostic tools for macular disease have developped over the last years due both
      to the elaboration of new methods of approach and to the improvement of the
      already existing ones. Fluorescein angiography (FA) is a minimally invasive
      procedure that involves photographic surveillance of the blood circulation of the
      retina and choroid, thus offering data on fundus pathology In eyes with AMD (Age
      Related Macular Degeneration) the assessment through FA is necessary in order to
      confirm the presence of CNV (Choroidal Neovascular Membrane). Beside that, FA
      offers details about the size, location and type (occult or classic) of CNV and
      it is useful in the followup after treatment. OCT (Optical Coherence Tomography)
      is a modern imagistic method, that is non-invasive, easily repetable and lacks
      complications. It acquires in vivo images that represent cross-sections of the
      retina. In the last years it has become an ever more popular diagnostic tool. OCT
      imaging is able to detect the presence of CNV and of sub- and intraretinal fluid
      accumulation. During the last decade, the management of neovascular AMD has
      changed, as anti-VEGF therapy has become the treatment of choice for all
      subfoveal CNV lesions types (occult and classic). Some clinicians tend to
      overlook the importance of FA assessment and rely only on visual acuity and OCT
      imaging for establishing both diagnosis and indication of treatment. Experts in
      the field say that these two investigations provide complementary information.
      They agree that the anatomical data offered by OCT imaging should be supported by
      the proof that an active exudation exists, which can only be provided by FA. At
      this moment the management of AMD includes both FA and OCT scanning. Several
      studies have tried to determine which OCT parameters corelate best with the
      activity of CNV as it appears on FA photographs. Further on, we shall present a
      few clinical cases that we consider representative for the topic.

PMID- 21888072
TI  - [Representation and mathematical analysis of human crystalline lens].
AB  - The surface of human crystalline lens can be described and analyzed using
      mathematical models based on parametric representations, used in biomechanical
      studies and 3D solid modeling of the lens. The mathematical models used in lens
      biomechanics allow the study and the behavior of crystalline lens on variables
      and complex dynamic loads. Also, the lens biomechanics has the potential to
      improve the results in the development of intraocular lenses and cataract
      surgery. The paper presents the most representative mathematical models currently
      used for the modeling of human crystalline lens, both optically and
      biomechanically.

PMID- 21888073
TI  - [Representation and mathematical analysis of human corneal surface].
AB  - In the description and analysis of human corneal surface are used various
      mathematical models based on parametric representations, used in biomechanical
      studies and 3D solid modeling of the cornea. Mathematical models are important
      into the biomechanics of the cornea to model the corneal behavior. Corneal
      biomechanics also has the potential to improve outcomes in refractive surgery.
      The objective of this paper is to present the most representative mathematical
      models currently used for modeling of human corneal in optics and biomechanics
      fields.

PMID- 21888074
TI  - [Adult onset foveomacular vitelliform dystrophy].
AB  - We present the case report of a 43 years old patient with adult-onset
      foveomacular vitelliform dystrophy, a rare disease described for the first time
      by Gass in 1974. The differential diagnosis was made particularly with Best
      disease, based on the aspect, the progression of the macular lesions, and the
      EOG.

PMID- 21888075
TI  - [Pneumosinus dilatans--general considerations and a case report].
AB  - The term "pneumosinus dilatans" was coined by Benjamin in 1918 in his description
      of ballooning hyperpneumatization of the frontal sinus. The term was use later on
      for excessive pneumatization of individual or several paranasal sinuses, with or
      without local compressive signs. Inspite of numerous publications, the phenomenon
      of pneumosinus dilatans of paranasal sinuses never became particularly popular.
      The diagnosis of sphenoid pneumosinus dilatans in particular was difficult to
      establish by conventional radiological methods and demonstration of the indirect
      signs of a compressive mechanism was almost impossible prior to the introduction
      of thin section CT. The etiology and pathogenesis of pneumosinus dilatans were a
      matter of speculation and remained unsatisfactory to researches and clinicians. A
      28-year-old male had a six-year history of scotoma and loss of the temporal
      visual fields for both eyes; he was admitted to Ophthalmological Department with
      visual loss of the right eye. The section CT was performed and revealed massive
      hyperpneumatization of the sphenoethmoidal sinusal complex, extending into the
      right anterior clinoid process, causing narrowing of the optic canal, more marked
      on the right than on the left side. The final diagnosis was: Right eye - Vitreous
      hemorrhage. Pneumosinus dilatans.

PMID- 21888076
TI  - [Paralysis of the oculomotor nerve caused by aneurysm--general facts and a case
      report].
AB  - One of the most frequent etiology of oculomotor nerve palsy are intracerebral
      aneurysms. Due to anatomical facts (its course and main relations with vascular
      structures of the brain) lesions of the oculomotor nerve often occur. In this
      paper there are presented essential issues concerning neuroanatomy of the III-rd
      cranial nerve pair main locations of the cerebral aneurysms in order to
      investigate the effect of nerve compression, clinical data regarding the palsy of
      the oculomotor nerve due to a cerebral aneurysm, the treatment and post surgery
      recovery followed by a clinical report.

PMID- 21888077
TI  - [Results in neovascular glaucoma treatment].
AB  - This report presents the results of a study on 34 patients with neovascular
      glaucoma. We analyse the difficulties and the results of the management of this
      severe form of glaucoma.

PMID- 21888078
TI  - [Surgically induced astigmatism in small incisions].
AB  - Surgically induced astigmatism (SIA) may represent one of the factors that could
      contribute to the patient's postoperative dissatisfaction, especially in the case
      of multifocal implants. In the case of the Restore implant, an astigmatism
      exceeding 0.75 D may consistently worsen the quality of the vision (Packard).

PMID- 21888079
TI  - [Effect of hemodialysis in retinal circulations].
AB  - In patients with chronic renal failure undergoing hemodialysis were recorded and
      studied by various authors multiple eye damage with time. Studying the literature
      we conducted a study to assess the impact of intradialitic-interdialitic and
      postdialitic volemic game above the retinal circulation. By measuring diameters
      of retinal circulation after processing the digital fundus, we found that, 30
      minutes after hemodialysis session takes a degree of dilatation of retinal
      vessels, permanent vascular insult that can be responsible for stroke and
      ischamic eye and coronary diseases of these patients.

PMID- 21888080
TI  - [Guidelines on hand hygiene in health care institutions].
AB  - Healthcare associated infections (HCAI) are huge problem all over the world, and
      5-10% of all hospitalized patients will develop infection during hospitalization.
      From the times of I. P. Semelweiss we know that clean hands are the most
      important single factor that can decrease the number of HCAI. World Health
      Organization (WHO) has recognised this problem and developed Guidelines for hand
      hygiene in healthcare institutions. This also was the reason of developing
      Croatian national Guidelines. The main goal of the Guidelines was to decrease
      number of HCAI associated with the hands of healthcare workers. These Guidelines
      are meant for all healthcare workers and other hospital staff who come to the
      direct contact with patients. An interdisciplinary team of experts developed
      these Guidelines using WHO Guidelines, other existing guidelines and literature
      reviews for hand hygiene. Grades of evidence for specific recommendations were
      determined using CDC/HICPAC grading system. Categorization is based on existing
      data, theoretical basis, applicability and economic impact. After a broad
      discussion in different professional societies, Guidelines were accepted.
      Guidelines include recommendations for hand hygiene indications, hand hygiene
      technique, surgical hand preparation, choosing hand hygiene preparations, skin
      care, nails, glove use, patients and visitors hand hygiene, role of education, as
      well as role of healthcare institution and role of government. Furthermore, in
      the Guidelines the concept of "Five moments for hand hygiene" is explained in
      detail, and main literature data are presented.

PMID- 21888081
TI  - [Consensus guidelines for diagnosis, treatment and follow-up of patients with
      gastrointestinal stromal tumors].
AB  - Gastrointestinal stromal tumors are the most common mesenchymal tumors in
      gastrointestinal tract. They are often asymptomatic and discovered incidentally
      during endoscopic or barium studies. About 80% GISTs have a KIT (CD 117 antigen)
      gene mutation. Most affect exon 11, less commonly exon 9,13 or 17, that results
      in uncontrolled KIT signaling. This led to effective systemic therapies in the
      form of small molecule inhibitors of the receptor tyrosine kinase such as
      imatinib mesylat. With the purpose of providing standardized approach to rational
      and effective diagnostic and treatment algorithm in Croatia, a multidisciplinary
      session was organized. Results of the session are given in the form of Consensus
      guidelines.

PMID- 21888082
TI  - [Feasibility of alpha-blockers in chronic category III prostatitis].
AB  - Studies were identified on internet by searching on address:
      http://www.ncbi.nlm.nih.gov/pubmed/ with criteria that studies should be placebo
      controlled and randomized in trials of alpha-blockers in chronic category III
      prostatitis evaluated by symptom-score NIH-CPSI. From 13 clinical studies three
      were excluded because of not using NIH-CPSI, three were in Chinese language and
      two were congress abstracts. Analysed were five studies with four or five Jadad
      scale including 563 patients. Alpha-blockers alfuzosin, terazosin, tamsulosin and
      doxazosin have been used through 6 weeks and 6 months. Better results were
      accomplished by less selective alpha-blockers alfuzosin, terazosin and doxazosin
      through 3-6 months in patients having higher NIH-CPSI score and higher voiding
      score.

PMID- 21888083
TI  - [Adherence to American European Consensus Group classification criteria for
      Sjogren's syndrome in differential diagnosis of xerostomia].
AB  - The aims were to obtain epidemiological and etiological data on xerostomia in
      cross section of Croatian population, and to evaluate adherence to "American
      European Consensus Group" (AECG) classification criteria for Sjogren's syndrome
      (SSj), in order to identify possible need for improvements in differential
      diagnosis of xerostomia. A retrospective study among patients seen at the
      Department of oral medicine for complaints of dry mouth was performed. Three
      hundred and ninety-five patients met inclusion criteria. A data base was formed,
      comprising epidemiological, clinical and sialometric data, immunological,
      scintigraphic, ultrasonographic and histopathological findings of salivary
      glands, coupled with drug intake listings. Descriptive statistics were used for
      data analysis. Objective salivary hypofunction was found in 74% of our patients.
      The most common probable cause of xerostomia was side effect of pharmacotherapy.
      SSj was diagnosed in 6.7% of patients with xerostomia, whereas in another 8% of
      patients Sjogren's syndrome was strongly suspected, but labial gland biopsy
      wasn't performed, indicating a lack of adherence to AECG criteria for SSj
      diagnosis. Application of AECG criteria in differential diagnosis of patients
      with dry mouth is mandatory, as well as educating general practitioners, dentists
      and patients on xerogenic side effects of pharmacotherapy.

PMID- 21888084
TI  - [Osteochondral fracture of the patella after acute dislocation].
AB  - Acute patellar dislocation is a common injury in young athletes, which occurs due
      to inappropriate biomechanical relations and anatomic deviations in the area of
      knee joint. In these unfavorable conditions, abrupt and vigorous strain of the
      quadriceps muscle of the thigh may result in lateral patellar dislocation. A case
      is presented of a young male athlete with acute patellar dislocation and
      consequential osteochondral fracture. Although x-ray showed normal knee finding,
      typical history, clinical examination and magnetic resonance image of the knee
      indicated arthroscopy, which confirmed the diagnosis ofpatellar dislocation. The
      osteochondral fragment was found and fastened by screws, thus reconstructing the
      articular surface of the patella. Medial patellar stabilizers were strengthened
      and lateral stabilizers loosened, thus re-establishing its anatomic slide way. On
      second-look operation, the screws were removed. In this case, good anatomic and
      functional outcome was achieved by timely operative treatment, joint surface
      reconstruction and rehabilitation.

PMID- 21888085
TI  - [Leiomyomatous renal cell carcinoma - case report].
AB  - According to WHO tumor classification histological subtypes of renal cell
      carcinoma are clear cell, papillary and chromophobe carcinoma. Carcinomas that do
      not fit readily into one of the categories should be assigned as unclassified. In
      recent literature new and emerging entities are described; follicular, clear cell
      papillary and cystic, oncocytic papillary and leiomyomatous renal cell carcinoma.
      The last one is microscopically composed of areas resembling clear cell carcinoma
      with sheets of epithelial cells having abundant clear cytoplasm and areas of
      mature smooth muscle. There are few articles describing above mentioned new
      entity. Altogether 14 cases are reported. In time of the diagnosis our patient
      had leiomyomatous renal cell carcinoma and metastatic tumors in both pulmonary
      lobes.

PMID- 21888086
TI  - [Vitamin D: vitamin from the past and hormone of the future].
AB  - In the last decade there has been a rising recognition of potential clinical
      significance of the vitamin D. Vitamin D regulates about 3% of the human genome.
      Thus, vitamin D deficiency is common and high in various populations across the
      world including Croatia. In this paper vitamin D metabolism and up to date
      knowledge of vitamin D function in calcium metabolism, muscular function and in
      prevention of infection, malignancy, autoimmune and cardiovascular diseases is
      presented. Reasons for pandemic vitamin D deficiency and guidelines for vitamin D
      supplementation are given.

PMID- 21888087
TI  - [Clinical and pathophysiological patterns of otitis externa and overview of
      problematic cases].
AB  - Otitis externa can sometimes present itself as a difficult clinical problem, in
      cases such as unsuccessful outcome of usual therapy, prolonged duration of
      symptoms or frequent recurrencies with local or systemic complications. In these
      cases more attention should be focused on possible errors made in establishing
      the right diagnosis, incorrect sequence of applying therapeutical measures, or
      presence of unrecognized problems, including individual patient factors,
      characteristics of the pathogen, or other. In this article we present a case
      report of a 84-year-old patient with complicated otitis externa, together with a
      short review of physiology, patophysiology, diagnostic and therapeutical measures
      in external otitis, and suggest a possible clinical approach in the management of
      problematic cases.

PMID- 21888088
TI  - [100,000 lives can be saved per year in Europe--the new ERC guidelines on
      resuscitation 2010].

PMID- 21888089
TI  - [Vertebrobasilar insufficiency and obstructive sleep apnea].

PMID- 21888090
TI  - A fair deal in retirement.

PMID- 21888091
TI  - Counselling for nurses shocked and appalled by hospital deaths.

PMID- 21888093
TI  - New alliance will tackle barriers to dignified care of older people.

PMID- 21888092
TI  - Increase in non-NHS providers will drive down pay, warns college.

PMID- 21888094
TI  - Trust to end incentive payments for forensic mental health staff.

PMID- 21888095
TI  - Campaign shows that savings are possible without cutting jobs.

PMID- 21888096
TI  - We will be burnt out in three years.

PMID- 21888097
TI  - Paying attention.
AB  - Attention deficit hyperactivity disorder is often misunderstood. But nurse
      specialists are helping families cope with the condition.

PMID- 21888098
TI  - Puppy power.
AB  - Dogs have been used for many years to help people who are blind or have hearing
      loss. Now they are being trained to help people with medical conditions such as
      cancer, diabetes, seizures, Addison's disease and narcolepsy.

PMID- 21888099
TI  - An indispensible role.
AB  - Freezing the vacant posts of diabetes nurse specialists is affecting patient care
      and will cost the NHS more in the long run, warns a major charity.

PMID- 21888100
TI  - It makes scents.
AB  - Aromatherapy, and the claims made for it, is the subject of the second article in
      our six-part series on alternative and complementary therapies.

PMID- 21888101
TI  - One-page patient passport for people with learning disabilities.
AB  - People with learning disabilities can have negative experiences in hospitals. One
      of the key reasons for this is the lack of time available for staff to understand
      individuals' needs. This article describes the development and implementation of
      the one-page patient passport, designed to provide individualised information
      about the person for doctors, nurses and administrative staff. The results from a
      pilot evaluation indicate that the tool promotes high levels of support for
      people with learning disabilities on admission to and during their stay in
      hospital.

PMID- 21888102
TI  - Wound care for injecting drug users: part 2.
AB  - Part one of this article, published last week, examined the issues associated
      with injecting drug use and the overall management of patients presenting with
      injection drug-related wounds. In part two of this article, the focus is on the
      physical problems associated with injecting drug use, in particular the
      development of leg ulcers. The article provides nurses with practical guidance on
      assessment and management of leg ulcers, including compression therapy.

PMID- 21888103
TI  - Pulmonary tuberculosis: clinical features and patient management.
AB  - Pulmonary tuberculosis (TB) is a common infectious disease and a major cause of
      illness and death throughout the world, particularly in developing countries.
      This article explores the difference between latent TB infection and active TB
      disease, and discusses the pharmacological management of TB and issues around
      adherence to medication. Although TB is usually managed by specialist teams it is
      essential that all practitioners have an understanding of the signs and symptoms
      of the disease to ensure early referral and accurate diagnosis.

PMID- 21888104
TI  - Menopause.

PMID- 21888105
TI  - Keep on course.

PMID- 21888106
TI  - Nurses lead at every level here.

PMID- 21888107
TI  - Home truths.

PMID- 21888108
TI  - What public health professionals can learn from obese people.

PMID- 21888109
TI  - Disability and obesity.

PMID- 21888110
TI  - Obesity: a complex and frustrating challenge but is NICE guidance part of the
      problem as well as part of the solution?

PMID- 21888111
TI  - The importance of being weaned: from guidelines to practice.

PMID- 21888112
TI  - Obesity.

PMID- 21888113
TI  - On with the pennies, off with the pounds? The use of taxation policies in obesity
      prevention.

PMID- 21888114
TI  - Fiscal food policy: equity and practice.

PMID- 21888115
TI  - Ethnicity and obesity in the UK.

PMID- 21888116
TI  - Tackling maternal obesity: the challenge for public health.

PMID- 21888117
TI  - Community gardening and obesity.

PMID- 21888118
TI  - Building grass roots capacity to tackle childhood obesity.
AB  - AIMS: In recognition of the increasing problem of child obesity in London and
      elsewhere, we were commissioned to build capacity to tackle this major public
      health concern. This paper describes one of the outputs of this work: to develop
      and deliver effective brief intervention training on the subject of childhood
      healthy/unhealthy weight and obesity to be used by anyone who works with children
      and families, regardless of their job title or level of educational achievement.
      METHODS: A literature review informed the process. The slim evidence derived was
      combined with the expertise of an expert working group to develop clear learning
      objectives for training and then to develop a flexible one-day training programme
      suitable for delivery to mixed groups of participants, to meet the learning
      objectives. Evaluation was built into the programme by means of a questionnaire
      at the end of the training session and by the use of a structured reflective log
      to be returned by participants once they had put their training into practice.
      RESULTS: The training programme was delivered free of charge to over 560 people
      during the course of a Regional Public Health Group-sponsored project.
      Subsequently it has been delivered to several more audiences working in the NHS,
      local government and third sectors in London on a not-for-profit basis.
      CONCLUSIONS: The programme, based on best available evidence and clear evidence
      of needs, provides a low-cost evaluated intervention that permits people from
      diverse professional and occupational backgrounds to acquire the knowledge,
      skills and confidence needed to raise the subject of healthy and unhealthy weight
      with parents of primary school-aged children and signpost them to appropriate
      local facilities and services. Although developed in London, the programme may be
      used anywhere in the UK, with the substitution of local information about
      prevalence of overweight and obesity and about local services and facilities.

PMID- 21888119
TI  - Obesity, ergonomics and public health.
AB  - Obesity within today's workforce is increasingly recognized as a challenge for
      both public health professionals and ergonomists. The two disciplines share a
      scientific, evidence-based approach to practice and now have the opportunity to
      address a common health issue, namely obesity. This paper shows, through an
      overview of the current literature, how and where obesity is impacting on the
      workplace and how the health of the workforce is being affected. Ergonomics and
      public health priorities have been mapped and challenges suitable for the
      application of existing knowledge and further research have been identified.
      Areas of common endeavour, for example how sedentary work may be exacerbating
      obesity, have been identified as candidate topics for joint activity by
      ergonomists and public health professionals.

PMID- 21888120
TI  - Evaluation of Healthy Choices: a commercial weight loss programme commissioned by
      the NHS.
AB  - AIM: The aim of this study is to identify factors that influence successful
      weight loss in an NHS-funded commercial weight loss programme. METHODS: Baseline
      height, weight, body mass index (BMI), age, gender, address, date of referral,
      referrer and 12-week attendance and weight were measured. Participants were
      classified as having achieved successful weight loss if they had > 5% weight loss
      and 'completers' if they had attended at least 10 of the 12 free sessions.
      Logistic regression analysis was used to estimate predictors of successful weight
      loss. Predictors tested in regression analyses were initial weight, number of
      meetings attended, deprivation, age and gender. RESULTS: In total, 2,456 (87%) of
      referred participants were given vouchers to attend a commercial weight loss
      programme for 12 weeks. The majority of the participants were female and the mean
      age group was 45-54 years. Almost half (44%) of all patients referred had > 5%
      weight loss at 12 weeks. A statistically significant difference was found in the
      mean weight loss between completers (6.1 kg, SD 3.7) and drop outs (2.2 kg, SD
      2.5). Participants who had successful weight loss were significantly more likely
      to be older, male and in obese class I. They were also significantly more likely
      to have attended more meetings. CONCLUSIONS: Commercial weight loss programmes
      produce successful weight loss in the short term. There was no difference in
      successful weight loss between providers and deprivation quintiles. Age, gender,
      initial BMI and number of meetings attended are all predictors of successful
      weight loss.

PMID- 21888121
TI  - Can worksite nutritional interventions improve productivity and firm
      profitability? A literature review.
AB  - AIMS: This paper investigates whether and how worksite nutrition policies can
      improve employee productivity. METHODS: The questions are pursued through a
      literature review, including a systematic search of literature--combined with
      literature identified from backward references--on randomized controlled or quasi
      experimental worksite intervention trials and observational cross-sectional
      studies. Studies were selected on the basis of topic relevance, according to
      publication title and subsequently according to abstract content. A quality
      appraisal of the studies was based on study design and clarity in definition of
      interventions, as well as environmental and outcome variables. RESULTS: The
      search identified 2,358 publications, 30 of which were found suitable for the
      review. Several of the reviewed studies suggest that diet-related worksite
      interventions have positive impacts on employees' nutritional knowledge, food
      intake and health and on the firm's profitability, mainly in terms of reduced
      absenteeism and presenteeism. CONCLUSIONS: Well-targeted and efficiently
      implemented diet-related worksite health promotion interventions may improve
      labour productivity by 1%-2%. On larger worksites, such productivity gains are
      likely to more than offset the costs of implementing such interventions. These
      conclusions are subject to some uncertainty due to the relatively limited amount
      of literature in the field.

PMID- 21888122
TI  - STEPS approach allows patient to participate in decision making.

PMID- 21888123
TI  - Avoiding sore throat morbidity and mortality: when is it not "just a sore
      throat?".

PMID- 21888124
TI  - Copper intrauterine device vs. depot medroxyprogesterone acetate for
      contraception.

PMID- 21888125
TI  - Short course of antibiotics for acute otitis media treatment.

PMID- 21888126
TI  - Stress fractures: diagnosis, treatment, and prevention.
AB  - Stress fractures are common injuries in athletes and military recruits. These
      injuries occur more commonly in lower extremities than in upper extremities.
      Stress fractures should be considered in patients who present with tenderness or
      edema after a recent increase in activity or repeated activity with limited rest.
      The differential diagnosis varies based on location, but commonly includes
      tendinopathy, compartment syndrome, and nerve or artery entrapment syndrome.
      Medial tibial stress syndrome (shin splints) can be distinguished from tibial
      stress fractures by diffuse tenderness along the length of the posteromedial
      tibial shaft and a lack of edema. When stress fracture is suspected, plain
      radiography should be obtained initially and, if negative, may be repeated after
      two to three weeks for greater accuracy. If an urgent diagnosis is needed, triple
      phase bone scintigraphy or magnetic resonance imaging should be considered. Both
      modalities have a similar sensitivity, but magnetic resonance imaging has greater
      specificity. Treatment of stress fractures consists of activity modification,
      including the use of nonweight-bearing crutches if needed for pain relief.
      Analgesics are appropriate to relieve pain, and pneumatic bracing can be used to
      facilitate healing. After the pain is resolved and the examination shows
      improvement, patients may gradually increase their level of activity. Surgical
      consultation may be appropriate for patients with stress fractures in high-risk
      locations, nonunion, or recurrent stress fractures. Prevention of stress
      fractures has been studied in military personnel, but more research is needed in
      other populations.

PMID- 21888127
TI  - Information from your family doctor. Stress fractures.

PMID- 21888128
TI  - The geriatric assessment.
AB  - The geriatric assessment is a multidimensional, multidisciplinary assessment
      designed to evaluate an older person's functional ability, physical health,
      cognition and mental health, and socioenvironmental circumstances. It is usually
      initiated when the physician identifies a potential problem. Specific elements of
      physical health that are evaluated include nutrition, vision, hearing, fecal and
      urinary continence, and balance. The geriatric assessment aids in the diagnosis
      of medical conditions; development of treatment and follow-up plans; coordination
      of management of care; and evaluation of long-term care needs and optimal
      placement. The geriatric assessment differs from a standard medical evaluation by
      including nonmedical domains; by emphasizing functional capacity and quality of
      life; and, often, by incorporating a multidisciplinary team. It usually yields a
      more complete and relevant list of medical problems, functional problems, and
      psychosocial issues. Well-validated tools and survey instruments for evaluating
      activities of daily living, hearing, fecal and urinary continence, balance, and
      cognition are an important part of the geriatric assessment. Because of the
      demands of a busy clinical practice, most geriatric assessments tend to be less
      comprehensive and more problem-directed. When multiple concerns are presented,
      the use of a "rolling" assessment over several visits should be considered.
      Academy of Family Physicians.

PMID- 21888129
TI  - Atrial fibrillation: diagnosis and treatment.
AB  - Atrial fibrillation is the most common cardiac arrhythmia. It impairs cardiac
      function and increases the risk of stroke. The incidence of atrial fibrillation
      increases with age. Key treatment issues include deciding when to restore normal
      sinus rhythm, when to control rate only, and how to prevent thromboembolism. Rate
      control is the preferred management option in most patients. Rhythm control is an
      option for patients in whom rate control cannot be achieved or who have
      persistent symptoms despite rate control. The current recommendation for strict
      rate control is a resting heart rate of less than 80 beats per minute. However,
      one study has shown that more lenient rate control of less than 110 beats per
      minute while at rest was not inferior to strict rate control in preventing
      cardiac death, heart failure, stroke, and life-threatening arrhythmias.
      Anticoagulation therapy is needed with rate control and rhythm control to prevent
      stroke. Warfarin is superior to aspirin and clopidogrel in preventing stroke
      despite its narrow therapeutic range and increased risk of bleeding. Tools that
      predict the risk of stroke (e.g., CHADS2) and the risk of bleeding (e.g.,
      Outpatient Bleeding Risk Index) are helpful in making decisions about
      anticoagulation therapy. Surgical options for atrial fibrillation include
      disruption of abnormal conduction pathways in the atria, and obliteration of the
      left atrial appendage. Catheter ablation is an option for restoring normal sinus
      rhythm in patients with paroxysmal atrial fibrillation and normal left atrial
      size. Referral to a cardiologist is warranted in patients who have complex
      cardiac disease; who are symptomatic on or unable to tolerate pharmacologic rate
      control; or who may be candidates for ablation or surgical interventions.

PMID- 21888130
TI  - Information from your family doctor. Atrial fibrillation.

PMID- 21888131
TI  - Yellowish papules on a middle-aged man. Eruptive xanthoma.

PMID- 21888132
TI  - Comforting a grieving parent.

PMID- 21888133
TI  - Interrogating leprosy 'stigma': why qualitative insights are vital.

PMID- 21888134
TI  - Responding to the socio-economic implications of leprosy.

PMID- 21888135
TI  - Leprosy stigma: ironing out the creases.
AB  - Oft-cited as a deterrent to elimination of the disease, stigma is still a
      critical feature of the leprosy landscape leading to ostracism, loss of
      employment, loss of housing, ridicule and rejection from society. The reason for
      leprosy-stigma rests historically and culturally on the mythology about the
      disease's origin and transmission, and its aesthetic features such as the
      enigmatic physical disfigurement, and the distinctive ulcers consequent of
      untreated leprosy. While the literature on leprosy has been consistent in showing
      that stigma is a social complication of the condition worldwide, there is seldom
      recognition of processes of stigmatisation in broader contexts. Effective and
      sustainable interventions directed at curbing leprosy stigma and so improving its
      social course must, however, be informed by an appreciation of such contexts;
      particularly in the light of the goal to eliminate the disease worldwide.
      Examining stigma in the broader contexts of historical, social, economic,
      political contexts is the aim of this paper. The paper also has implications for
      broad ranging intervention efforts aimed at de-constructing leprosy-stigma in
      order to craft a more accommodating ambiance of acceptance, care and support for
      people affected by leprosy.

PMID- 21888136
TI  - Nuancing 'leprosy stigma' through ethnographic biography in South India.
AB  - Synoptic life history accounts and case studies of people with leprosy have
      tended to follow conventionalised narrative forms, with the onset of leprosy
      causing a violent rupture in otherwise positively construed life courses. Many of
      those I worked with in India, well-versed in relating their stories to donor
      agencies, were also aware of the power of such narratives to access funding.
      While case studies can be informative about the politics of representation, then,
      they often obscure as much as they reveal about the lives of those described
      within them, emphasising leprosy-related stigma at the expense of other forms or
      drivers of social exclusion. Drawing upon a series of interviews with a leprosy
      affected man I have known and worked with for 25 years, this paper demonstrates
      how more nuanced--and, from a policy perspective, more useful--accounts might be
      achieved through intensive biographical interviews carried out over time. In
      particular, analysis of such biographies, set against the wider backdrop of
      ethnographic research, allows for a more subtle reading of leprosy-related
      stigma, contextualised in relation to a range of intersecting socio-political,
      cultural and economic concerns.

PMID- 21888137
TI  - Leprosy in Eastern Nigeria and the social history of colonial skin.
AB  - To the historian, the 'historical' experience of leprosy control is not simply a
      backdrop to contemporary patterns or problems in disease control. The control of
      leprosy has been enacted in different ways in localities, territories and states
      across the world. The specific clinical, political, and institutional choices
      made in leprosy control have been highly significant in shaping attitudes and
      approaches to leprosy. The term stigma has a history of usage, contention and re
      definition. Stigma, then, is a product of its intersecting social, economic, and
      medical contexts. In order to capture the degree to which stigma associated with
      leprosy has mutated and changed over time, this article concerns itself
      specifically with the colonial experience of leprosy, with a focus on the
      formerly leprosy-endemic area of southeastern Nigeria (known as the Eastern
      Region, or Eastern Nigeria) in the last quarter century of colonial rule ending
      in 1960. The article examines how leprosy was presented, identifying some of the
      forms in which ideas of stigma and taint with respect to leprosy were
      communicated. It goes on to examine how leprosy was encountered as a medical
      problem in Eastern Nigeria, placing leprosy in the context of skin diseases most
      commonly encountered by colonial medical services. It concludes by demonstrating
      how leprosy was understood, looking briefly at local and biomedical means of
      identifying and combating these diseases, and the meanings of these diseases in
      the rapidly changing contexts of mid- and late-colonial rule and the onset of
      Nigerian Independence in 1960.

PMID- 21888138
TI  - Pride and prejudice--identity and stigma in leprosy work.
AB  - This article sets out to expand the way stigma, and those affected by it, are
      understood within leprosy discourse and to apply these insights to the analysis
      of the experiences of leprosy workers. The term stigma is often used simply as
      shorthand for 'negative social experience'. However, to reduce the negative
      aspects of complex everyday life experiences to a single word is often overly
      simplistic and can serve to objectify, rather than illuminate, the experiences of
      those affected. This article argues that in order to understand the lived
      experience of stigma we must come to understand stigma as an ongoing, dialectical
      social process and develop an approach to stigma that analytically separates
      stigma from its negative social consequences. The article applies these insights
      to data collected during 14 months of fieldwork with front-line leprosy workers
      in India, which suggests that falling leprosy prevalence rates and a rapidly
      changing policy landscape have led to leprosy workers feeling marginalised and
      stigmatised within their own organisation. The article argues that, rather than
      seeing stigma merely as a negative process in which leprosy workers are passive
      victims, we must recognise that stigma also plays a key role in the creation and
      maintenance of leprosy workers' identity and is utilised as a strategic tool in
      the struggle for influence between different groups within the organisation.
      Finally, the article argues for the benefit of expanding our understanding of
      stigma across public health and of applying these insights to designing future
      interventions.

PMID- 21888139
TI  - Leprosy and stigma in the context of international migration.
AB  - If it can be argued that no single attribute or condition (leprosy included) is
      inherently or universally considered to be 'deeply discrediting,' to quote
      Goffman, then we must consider how external factors shape stigma associated with
      that condition in different cultural and socioeconomic contexts. Often, an
      analysis of what is perceived to be stigma towards people affected by leprosy
      uncovers other prejudices or stigmatising attitudes associated with class,
      gender, and/or ethnic inequalities in that society. The movement of people across
      international borders adds new dimensions to the experience of leprosy, as
      affected individuals confront different sets of understandings of the disease
      among healthcare professionals, friends, family, and employers in host and
      sending countries. Preconceptions of the immigrant 'other' in host countries may
      be bound up with notions of disease and danger, further complicating the
      experience of leprosy treatment for immigrants. Drawing on the work of others and
      on early stage qualitative research on leprosy among Brazilian immigrants to the
      United States, this paper will consider the ways in which immigration and
      transnational processes could affect the experience of stigma among immigrants
      affected by leprosy.

PMID- 21888140
TI  - Leprosy, the key to another kingdom.
AB  - OBJECTIVE: In India, many people affected by leprosy still live in self
      established settlements, commonly referred to as leprosy colonies. Aid
      organisations generally attribute the social segregation of colony members to the
      stigma attached to leprosy. In this article, I argue that the common approach
      towards leprosy colonies is actually based on a limited understanding of social
      relations between colony members and others. The insights from this study will
      hopefully facilitate re-thinking current approaches to stigma reduction in
      leprosy. DESIGN: An ethnographic study conducted over a period of three months in
      and around a leprosy colony in India. With the help of a local research
      assistant, I carried out semi-structured interviews, informal conversations, and
      participant as well as non-participant observation. I conducted interviews with
      22 colony members and 25 residents from the adjacent neighbourhoods of the
      colony. RESULTS: This study reveals that the differentiation between colony
      members and others derived at least as much from community membership as from
      stigma. Leprosy-affected people living outside the colony, for example, perceived
      the colony members as widely different from themselves, whilst stigma affected
      both groups. Programmes with the aim of reducing stigma need to approach stigma
      relations as embedded in various interrelated physio-emotional and socio-cultural
      processes, rather than approaching social aspects of leprosy by focusing
      exclusively on the notion of stigma.

PMID- 21888141
TI  - Social implications of leprosy in the Netherlands--stigma among ex-leprosy
      patients in a non-endemic setting.
AB  - BACKGROUND: In the Netherlands, leprosy is a rare and non-endemic disease, still
      occurring as an 'import disease'. Moreover a considerable group of people
      affected by leprosy, originating mainly from the former Dutch colonies, suffer
      from neuropathic complications. This study investigates the social implications
      of leprosy for those affected in the Netherlands. METHODS: Thirty-one people
      affected were interviewed as well as six medical leprosy experts. The social
      implications were measured by means of semi-structured interviews and the
      Participation Scale. RESULTS: Self-stigma, shame and secrecy were often reported.
      Discrimination and stigmatisation of ex-leprosy patients by people around them
      seems a less frequent problem. Yet, people affected by leprosy seem to be a
      forgotten group with a high social burden due to low self-esteem and reduced
      social participation. Medical experts do not seem to be aware of the severity of
      leprosy-related forms of stigma in their patients. Ex-leprosy patients lack sound
      disease-related information and support groups. Due to the low incidence and as a
      consequence, the lack of awareness among doctors, leprosy patients in the
      Netherlands are faced with substantial diagnostic delay (mean delay 1-8 years).
      CONCLUSIONS: Leprosy and its stigma affect the social lives of patients, even in
      a non-endemic area such as the Netherlands. Almost all respondents were affected
      by self-stigma. There is a need for 1) more information and support groups for
      patients, and 2) increased awareness among professionals.

PMID- 21888142
TI  - Acceptability of chemoprophylaxis for household contacts of leprosy patients in
      Bangladesh: a qualitative study.
AB  - OBJECTIVES: Chemoprophylaxis with single dose rifampicin is a promising
      intervention to prevent leprosy in close contacts of patients. However,
      application in control programmes often requires disclosure of the leprosy
      diagnosis, which is still a stigmatised disease in many countries. Promoting
      control and treatment of stigmatised diseases without contributing towards stigma
      of the individuals involved can be very difficult. The objective of this study
      was to assess the social acceptability of disclosure of the diagnosis and the
      attitude towards taking prophylactic medicines in a leprosy endemic area in
      Bangladesh. DESIGN: Qualitative study through focus group discussions with 136
      healthy men and women from different age groups and religions, coming from two
      rural villages and an urban area in northwest Bangladesh, and 14 health workers
      with extensive experience with leprosy patients. RESULTS: The participants would
      not object to disclosure of the diagnosis to household members and nearby family
      if they were diagnosed with leprosy. However, many participants were not willing
      to share this information with their neighbours and other social contacts due to
      stigma of the disease. All healthy participants were willing to take
      chemoprophylaxis if any of their close contacts were diagnosed with leprosy, even
      after explaining that full protection against leprosy was not guaranteed.
      CONCLUSION: It can be concluded that chemoprophylaxis for household contacts of
      leprosy patients is an effective and socially acceptable addition to the current
      leprosy control programme. Chemoprophylaxis for other categories of contacts
      likely to benefit would only be feasible, without disclosure of patient
      information, if given in the form of mass campaigns for the whole population in
      the area.

PMID- 21888143
TI  - Report of the Stigma Research Workshop for the development of scientific
      consensus papers and field guidelines on health-related stigma, held in
      Amsterdam, the Netherlands from 11-14 october 2010.
AB  - Summary In concurrence with the broad body of literature published on health
      related stigma, there is a need for practical field guidance to contribute to the
      fight against leprosy-related stigma and discrimination. To this end, much can be
      gained by considering the accumulated knowledge and learned from experience with
      different stigmatising conditions; primarily HIV/AIDS, disability, tuberculosis,
      and mental health. Therefore a Stigma Research Workshop was organised from 11-14
      October in Amsterdam, The Netherlands. The primary aim of the workshop was to
      produce scientific papers and field guidelines that could be used to target
      actions against health-related stigma and discrimination. Keynote presentations
      were offered by scientists and professionals from different health domains who
      shared their knowledge, experiences and research findings regarding health
      related stigma. Group work was subsequently conducted to work towards agreed
      outputs on four different themes: i.e. research priorities, measurement,
      interventions, and counselling. The spectrum of expertise present enabled an
      interdisciplinary and inter-profession sharing of knowledge and practices. This
      resulted in the commencement of consensus papers and field guidelines related to
      the four themes. An evaluation by participants concluded that the workshop had
      been an informative and worthwhile activity that will strengthen the fight
      against stigma.

PMID- 21888144
TI  - How African-Americans fare with susceptibility to disease: forty years after the
      founding of the NBNA.

PMID- 21888145
TI  - African-American males' knowledge and attitudes toward genetic testing and
      willingness to participate in genetic testing: a pilot study.
AB  - This descriptive pilot study explored the knowledge and attitudes of African
      American males toward genetic testing and their willingness to participate in
      genetic testing. A convenience sample of 104 African-American males, from 19 to
      79 years of age, was recruited from a national fraternity meeting. Data were
      collected using four surveys: Demographic and Background Data, Perceived
      Knowledge of Genetic Testing, Attitudes Toward Genetic Testing, and Willingness
      to Participate in Genetic Testing. Perceived genetic knowledge was low with a
      mean score of 5.6; however, participants had a favorable attitude toward genetic
      testing. Findings from this study suggested that participants were willing to
      participate in genetic testing with a total score of 46.8. Significant
      correlations existed between perceived genetic knowledge and willingness to
      participate in genetic testing. Interventions to increase perceived genetic
      knowledge and educate the participant on who is conducting the test and how the
      test will be performed may be beneficial to increase participation in genetic
      testing.

PMID- 21888146
TI  - Factors associated with why African-American women from one urban county use
      mammography services less.
AB  - A two-group comparison pilot study was conducted with 60 (N = 60) U.S. born
      African-American women to determine the factors associated with decreased
      utilization of mammography among women who have access to mammography services,
      yet choose not to utilize them. Findings from the study suggest that African
      American acculturation and Health Temporal Orientation were significantly
      associated with mammography utilization (p = 0.01). There was no significant
      relationship between other cultural beliefs, health-care avoidance, or
      sociodemographic status indicators. Six content areas also emerged from a focus
      group discussion associated with barriers/factors related to mammography
      utilization. Findings from this study also suggest that further research and
      outreach is needed to address the development of tailored interventions to
      increase the rate of mammography utilization and reduce the incidence and
      mortality related to breast cancer in African-American women.

PMID- 21888147
TI  - A descriptive study: weight management practices of members of a professional
      nursing association who were trying to lose weight.
AB  - In the United States, obesity has reached epidemic levels. A critical challenge
      today is improving the health behaviors of those providing care to the general
      public. This descriptive quantitative study sought to describe the weight
      management practices of members of a professional nursing association who were
      trying to lose weight. Questions were adapted from the Behavioral Risk Factor
      Surveillance Survey (Centers for Disease Control and Prevention [CDC], 2001
      2010). In addition, the HealthStyles survey (Pollard, 2002; Kruger, Blanck, &
      Gillespie, 2006) was used along with one additionally inserted question. Data
      were analyzed with descriptive statistics, one-way ANOVA, Pearson Product Moment
      Correlation, and a Spearman Rho. Findings suggested that a small percentage of
      the nurses moved from the obese classification into the overweight status,
      thereby improving their health. Over 60% of the nurses attempted to lose weight
      by combining dietary and exercise strategies. Forty-one percent of the nurses met
      the recommended physical activity guidelines of the American College of Sports
      Medicine (ACSM) to maintain health and to reduce the risk for chronic disease,
      but in order to lose weight, only 13% met the recommended 60-90 minutes of
      physical activity guidelines.

PMID- 21888148
TI  - Project genesis: self-reported religiosity and spirituality and sexual risk
      taking in young African-American women attending a historically African-American
      college.
AB  - This pilot study explored the relationship between self-reported religiosity,
      spirituality, and sexual risk-taking. The participants were a convenience sample
      of (N = 100) female students attending a historically African-American college
      (HBCU) in the south. On this predominantly female campus, students completed an
      anonymous health-risk survey, plus additional items, to measure their religiosity
      and spirituality. Correlation analysis revealed that although these students
      reported a high degree of religiosity and spirituality, these characteristics did
      not predict a decrease in sexual risk-taking behavior. Over six million new cases
      of sexually transmitted infections (STIs), including the human papilloma virus
      (HPV), are projected in young Americans despite primary prevention measures.
      Although no predictive relationships were noted, self-reported spirituality or
      religiosity were not protective factors against high-risk sexual behavior. These
      findings are relevant to developing effective interventions in this population in
      order to decrease STI/HPV rates.

PMID- 21888149
TI  - The influence of urban literature on African-American adolescent girls' sexual
      behaviors.
AB  - Many African-American teenaged girls are reading urban literature. This genre of
      literature is known for its gritty portrayal of urban life and has themes of
      violence, promiscuity, substance abuse and misogyny. Although research has
      demonstrated that the portrayal of sex and violence in the media are influential
      on adolescent sexual behavior, to date there has been little research on the
      influence of "urban lit" on adolescent sexual risk behaviors. This qualitative
      study explores the influence of urban literature on the sexual risk behaviors
      among a group of African-American adolescent girls. Findings from this study
      suggest that African-American adolescent girls may be influenced by the sexual
      themes depicted in this genre of literature. Additional research is needed to
      gain a greater understanding of this phenomon.

PMID- 21888150
TI  - Physicians' and nurses' experiences of the influence of race and ethnicity on the
      quality of healthcare provided to minority patients, and on their own
      professional careers.
AB  - This qualitative content analysis examines data from African-American and
      Hispanic physician and nurse focus groups conducted by the Institute of Medicine
      (IOM). Participants discussed the influence of race and ethnicity regarding
      perspectives on healthcare provided to ethnic minority patients, and on the
      professional careers of ethnic minority physicians and nurses. A majority of
      responses related to Racism and Prejudice, which affected ethnic minority
      patients and health-care providers at three levels (health-care system to
      patient, provider to patient, and provider to provider). Racism and Prejudice
      interfered with promotions, obtaining hospital privileges, and advancement in
      careers. Communication and Culture was important among patients who preferred
      racially concordant care providers. Role Modeling was found to be important as
      participants entered and matured in their professional careers. Findings provide
      compelling evidence that racism and prejudice are shared experiences between
      ethnic minority physicians and nurses throughout their careers. One concerning
      finding was that perceived prejudice materialized at the onset of medical and
      nursing education and remained a predominant theme throughout the professionals'
      careers. Research should be directed towards providing equity in care and on the
      careers of ethnic minority health-care professionals.

PMID- 21888151
TI  - Issues in community-based care among homeless minorities.
AB  - Homelessness is an increasing major public health problem in the United States.
      The homeless population consists of men, women, youth and families who live on
      the streets or in shelters. Minorities, especially African-Americans and
      Hispanics, are particularly at risk for homelessness due to their high rates of
      poverty. Homelessness predisposes persons to poor health, including a variety of
      acute and chronic physical and psychological diseases for which they often have
      difficulty obtaining healthcare. This article discusses common issues and
      challenges that homeless minorities and their health-care providers face in
      obtaining community-based healthcare, including issues in caring for homeless men
      and women, fragmentation of healthcare, perceived discrimination and provider
      bias, provider-patient trust issues, lack of access to care, and health literacy
      issues. Two programs designed to provide community-based experiential learning
      for nursing students to address these issues and the health-care needs of the
      homeless are described, i.e., the Men Achieving Self Health (MASH) and Women
      Inspired Self Health (WISH) Outreach Programs. Approaches used by faculty and
      students who are engaged in providing health-care services to the homeless via
      the MASH and WISH Programs are discussed.

PMID- 21888152
TI  - Robotics--the future of surgery.

PMID- 21888153
TI  - Clinical profile of epilepsy, in a tertiary care centre of North-west India.
AB  - The present study has been undertaken in a tertiary care centre of North-west
      India to know the clinical profile of epilepsy and response to drug therapy with
      special reference to study the effect of reduction of dosage of anti-epileptic
      drug after a seizure-free interval of two years. A total of 904 patients were
      selected during the period January, 2001 to October, 2006 who attended OPD clinic
      of the department of neurology, SMS Medical College and Hospital, Jaipur.
      Datailed clinical history was taken, general physical examination, routine blood
      examination, ECG and CT scan along with MRI (brain) in some cases were carried
      out. Of all the cases, sex ratio (male : female) was 2:1. A high proportion of
      cases (62.83%) were from low socio-economic group, 41.15% had normal EEG, 532
      patients had normal CT scan (out of 800 cases). Single drug therapy was
      instituted in 71.67% cases. Patients went follow-up for 3 years. Most of the
      cases proved to be seizure-free after 2 years. Average maintenance dosage in
      patients on monotherapy can be reduced after a seizure-free interval of 2 years.

PMID- 21888154
TI  - An epidemiological analysis of patients with abdominal trauma in an eastern
      Indian metropolitan city.
AB  - The profile and pattern of abdominal trauma is changing with progressing
      civilisation. We are lacking epidemiological data from most parts of the world.
      This study was conducted to prepare a database in our set up and look into the
      pattern of abdominal trauma, make an aetiological correlation of abdominal trauma
      with the types of injuries, identify the preventable factors causing delay in
      intervention and, compare the data with the other available national and
      international data. This prospective, observational study was done in a teaching
      hospital in a metropolitan city of eastern India. Records of patients with
      abdominal trauma were collected in predesigned forms, from admission to
      discharge. Data were analysed applying standard statistical techniques. Males
      (87.3%) predominated with the age range between 21 and 30 years, and the majority
      (73.5%) had blunt abdominal trauma. Compression injury (57.3%) commonly caused
      blunt trauma and stab injuries caused majority of penetrating trauma. The
      commonest organ injured both in blunt and penetrating trauma was small bowel
      (30.7% and 33.3% respectively). It was found that prehospital trauma care is
      virtually non-existent in this region. We are lacking a uniform protocol for the
      management of abdominal trauma across the hospitals. With the availability of
      better investigational modalities we are moving more towards a conservative
      approach to the abdominal trauma patients, especially the blunt abdominal trauma
      patients with solid organ injuries.

PMID- 21888155
TI  - Intra-operative myocardial ischaemia and infarction in patients with coronary
      artery disease undergoing prostatectomy/cholecystectomy.
AB  - Fifty patients over the age of 40 years of either sex (28 males and 22 females)
      having definite coronary artery disease as indicated by history of previous
      myocardial infarction, angina or ECG evidences of myocardial infarction (silent
      myocardial infarction), undergoing non-cardiac surgery were studied. In order to
      detect the incidence of myocardial ischaemia during the peri-operative period,
      continuous monitoring of electrocardiogram was performed in all patients for 24
      hours, beginning from the morning of surgery using a 2-channel Holter recorder.
      Intra-operative events besides myocardial ischaemia were noted. CK-MB isoenzyme
      assay was done on days 0, 1, 2, 3, 5, 7 postoperatively in all patients. CK-MB
      and ECG were also done whenever indicated. The incidences of intra-operative and
      postoperative ischaemia were 40% and 48% respectively. The incidence of
      postoperative myocardial ischaemia in patients with intra-operative myocardial
      ischaemia was found to be significantly higher than those patients without intra
      operative myocardial ischaemia. The rate of myocardial ischaemia and peri
      operative myocardial infarction was lower in patients on beta-blockers than those
      patients who were not on these drugs though a statistical difference was not
      reached. The rate of peri-operative myocardial infarction was also found to be
      higher in patients who had intra-operative hypertensive or hypotensive episodes
      though a statistical significance was not reached. Patients who had either pre
      operative or peri-operative myocardial ischaemia had greater incidence of peri
      operative myocardial infarction than those patients without myocardial ischaemia
      but the difference was not statistically significant.

PMID- 21888156
TI  - National guidelines for diagnosis and management of dengue fever/dengue
      haemorrhagic fever and dengue shock syndrome.

PMID- 21888157
TI  - Serotonin syndrome in maintenance haemodialysis patients following sertraline
      treatment for depression.
AB  - Sertraline, a selective serotonin reuptake inhibitor (SSRI), was used in a dose
      of 25 mg orally daily in 12 moderate to severely depressed patients of end stage
      renal disease (ESRD) on maintenance haemodialysis. Virtually all of them showed
      features of hyperserotonin state and in 11 drug was stopped within 3 weeks. One
      of the patients developed almost fatal serotonin syndrome and required intensive
      care with ventilatory support. In our experience the use of SSRI, sertraline for
      depression in ESRD patients on maintenance haemodalysis was associated with a
      high incidence of serotonergic side-effects and toxic serotonin syndrome.

PMID- 21888158
TI  - Telecommunication technology used in home healthcare.
AB  - Current telemedicine applications are usually developed for doctors to do
      consultation and case study between several hospitals. Patients see doctor at
      home via Internet becomes possible and it might be a part of lifestyle in the
      future. Telemedicine has been an active area of research for over 30 years. In
      the past, several telemedicine applications using wired EPABX telecommunications
      equipment were provided whereas now-a-days the evolution of wireless
      communication means enabling telemedicine systems to operate everywhere in the
      world, thus expanding telemedicine benefits, services and applications. How these
      applications are used in healthcare delivery and what are the technologies used
      in this system are explained in this paper.

PMID- 21888159
TI  - HIV-TB: the 'cursed duet'.
AB  - Tuberculosis is the most common infection among HIV-infected patients in India.
      More deaths were reported due to tuberculosis in AIDS patients in pre
      antiretroviral therapy era. HIV is the strongest of all known, risk factors for
      the development of TB. Tuberculosis can develop at any stage of the HIV disease.
      Extrapulmonary tuberculosis is more common and constitues half of the cases in
      HIV-infected individual with TB. Hilar lymphadenopathy is frequently observed. TB
      in HIV frequently poses a diagnostic challenge. Acid-fast bacillus demonstration
      on sputum smear microscopy is the main-stay laboratory investigation for TB. In
      addition to antituberculous therapy, antiretroviral therapy must be initiated in
      HIV-infected individual with TB. Early referrals to the RNTCP and ART programmes
      are the best option for management.

PMID- 21888160
TI  - Women and HIV/AIDS.
AB  - Out of 39 million people in the world, currently living with HIV or AIDS, half
      are women. Of the 45 million new cases expected between 2002 and 2010, 70% likely
      to be women. Therefore women empowerment and awareness about the HIV/AIDS are
      mandatory and need of the day for control of AIDS. Women must take control of HIV
      prevention to curb spread of infection.

PMID- 21888161
TI  - Tuberculous meningo-encephalitis mimicking herpes simplex encephalitis on MRI.
AB  - A 30-year-old man was admitted in PGIMER with the complaints of fever, altered
      sensorium and seizures. Magnetic resonance imaging (MRI) showed bilateral
      symmetrical temporal and frontal hyperintensities, which were highly suggestive
      of herpes simplex encephalitis. However, brain autopsy revealed it to be
      tuberculous meningo-encephalitis.

PMID- 21888162
TI  - Fracture of the penis--report of seven cases.
AB  - Fracture of the penis is an uncommon emergency consisting of rupture of the
      tunica albuginea of the corpus cavernosum resulting from blunt trauma over an
      erect penis. Prompt diagnosis and early surgical repair are essential to ensure a
      successful outcome with minimal complications. Delay may result in devastating
      physical and psychological disabilities that are potentially avoidable. Here in
      this article, 7 cases of fracture penis are being reported, who had been managed
      successfully by surgery in 6 cases and one case treated conservatively as he
      refused surgery.

PMID- 21888163
TI  - Hypothyroidism presenting as cardiac tamponade in Down syndrome.
AB  - Down syndrome is the commonest chromosomal anomaly. It is often associated with
      hypothyroidism, which may rarely present with cardiac tamponade as the earliest
      manifestation and prompt treatment with L-thyroxine is life saving. A six-month
      old female child diagnosed as a case of Down syndrome presented with shortness of
      breathing for last 1 1/2 months. Facial dysmorphism, characteristic of Down
      syndrome was present. Echocardiography revealed large pericardial effusion and
      right ventricular diagnostic collapse. A case of Down syndrome with
      hypothyroidism and cardiac tamponade was kept in mind. She was treated with L
      thyroxine and clinical status improved.

PMID- 21888164
TI  - A comparative clinical study of injection clonidine versus midazolam in
      supraclavicular brachial plexus block for sedation and postoperative analgesia.

PMID- 21888165
TI  - SILS--is it natural progression from multiport minimal access surgery?

PMID- 21888166
TI  - Prevalence of rheumatic conditions in patients with diabetes mellitus in a
      tertiary care hospital.
AB  - Musculoskeletal disorders are common in diabetic subjects. The pathophysiology of
      these disorders in diabetic patients is not obvious. It could be due to
      connective tissue disorders, glycosylated end products, vasculopathy, neuropathy
      or combinations. A wide range of musculoskeletal syndromes have been described in
      association with diabetes, namely diabetic cheiro-arthropathy, adhesive
      capsulitis of shoulder, carpal tunnel syndrome, Dupuytren's contracture,
      hyperostosis, osteo-arthritis, hyperuricaemia, etc. This study was undertaken to
      find out the prevalence of these conditions in diabetes mellitus and to look for
      any associations with diabetic complications or therapy. A tertiary care centre
      based cross-sectional study was carried out among 100 consecutive diabetic
      patients (WHO criteria) attending medicine department who were enrolled. The
      study was done at Calcutta National Medical College and Hospital, Kolkata, from
      March 2008 to February 2009. The diagnoses of the rheumatic conditions were made
      by unbiased clinical observations on the basis of standardised case definitions
      or criteria. Limited joint mobility (29%), adhesive capsulitis (18%), and osteo
      arthritis of knee (27%) or hand (17%) were the most common rheumatic conditions
      in diabetics. Trigger finger (flexor tenosynovitis) and carpal tunnel syndrome
      were also present in 7% and 5% cases of diabetics respectively. Although
      hyperuricaemia was present in 9%, clinical gout was present in only 4%. There was
      no clear association of these syndromes with diabetic renal disease or micro
      albuminuria. Most of these conditions were noted in chronic long duration
      diabetic subjects.

PMID- 21888167
TI  - Study of referral pattern to ophthalmology outpatient department from various
      departments in the medical college.
AB  - The study was aimed at finding out the pattern of referrals to ophthalmology
      outpatient department (OPD) in a teaching hospital and to provide guidelines for
      the improvement. Patients referred from various departments of a medical college
      situated in central India for ophthalmic evaluation were scrutinised for age,
      sex, diagnosis and the referring OPD. Out of 730 patients referred, 350 (47.95%)
      were males and 380 (52.02%) were females. The highest referral was found in the
      age group 45-64 years (22.60%). The highest referral was from the medicine OPD
      (58.22%) and the lowest was from psychiatry (2.05%). Maximum patients were
      referred for fundus examination (27.40%). While there were 280 patients (38.36%)
      who had refractive error, no diagnosis was established in 147 cases (20.14%).
      Ophthalmic opinion definitely helped patients as well as physician in the
      management of the patients. The study also stresses on some areas deficient, when
      unnecessary referrals could be avoided by arranging short annual refreshers
      courses to acquire basic skills in ophthalmology like visual acuity testing,
      colour vision, ophthalmoscopy and the diagnosis of common ocular conditions. We
      believe this kind of activity will help to make our services more efficient and
      cost effective.

PMID- 21888168
TI  - Epidemiology of dengue, its prevention and control in India.

PMID- 21888169
TI  - Elimination of malaria--challenges in India.

PMID- 21888170
TI  - World Kidney Day 2011 : protect your kidneys, save your heart.
AB  - World Kidney Day is observed on March 10 every year and in 2011 the 6th annual
      event is going to be celebrated under the joint sponsorers - International
      Society of Nephrology and the International Federation of Kidney Foundations. The
      presence of chronic kidney disease significantly increases the risk of a
      cardiovascular event in both diabetes and hypertension. Proteinuria is always a
      marker of kidney disease. The time to development of a cardiovascular event is
      accelerated significantly by the presence of proteinuria at all levels of
      glomerular filtration rate. It is suggested that renal-targeted interventions
      designed to reduce proteinuria and slow progression of chronic renal disease can
      reduce cardiovascular disease. The biomarkers of chronic kidney disease
      (proteinuria, eGFR) are easy and relatively inexpensive to detect and one of
      these, proteinuria emerges early in the generalised vascular disease.

PMID- 21888171
TI  - Clinicopathologic profile of non-Hodgkin's lymphoma in a rural medical college.
AB  - A prospective study was done at North Bengal Medical College, Sushrutanagar,
      Darjeeling, West Bengal over a period of two years. All patients diagnosed as non
      Hodgkin's lymphoma were analysed for clinical presentation, classified according
      to the Working Formulation and staged according to Ann Arbor staging system. A
      lower median age (39.94 years) of onset and higher male to female ratio (3.22:1)
      as compared to western countries were observed. We found neck swelling was the
      commonest presenting symptom (65.79%) and peripheral lymphadenopathy was the
      commonest sign (94.74%). "B symptoms" were noted in 63.16% cases. Cervical lymph
      nodes were commonly involved (78.95%), followed by axillary (55.26%). Thoracic
      lymph nodes were enlarged in 31.58% cases and abdominal lymph nodes in 18.42%
      cases. We found diffuse mixed variant was the commonest (31.58%) followed by
      diffuse large cell (18.42%). At presentation most of the cases were of
      intermediate grade (55.26%) and in stage III (44.74%). We conclude that there is
      a distinct geographical pattern of non-Hodgkin's lymphoma in respect of age, sex,
      grade and stage of the disease which is distinctly different from those of
      western countries.

PMID- 21888172
TI  - Unusual origin and variation in topographical relation of inferior alveolar nerve
      in the left infratemporal region.
AB  - The inferior alveolar nerve and its topographical relation with the maxillary
      artery during routine dissection in the department of anatomy, Dayanand Medical
      College and Hospital, Ludhiana was studied in 50 infratemporal fossae. In one
      specimen an unusual variation in the origin of inferior alveolar nerve was found.
      The inferior alveolar nerve in this case originated from the mandibular nerve by
      two roots. Its relationship with the maxillary artery also showed variation. The
      second part of maxillary artery was passing between the two roots of inferior
      alveolar nerve. An embryological basis of this variation and its clinical
      implication is discussed.

PMID- 21888173
TI  - Acute gastric volvulus: a report of eight cases.
AB  - Acute gastric volvulus is an abnormal rotation of the stomach through 1800. This
      study illustrates a series of 8 patients who underwent operative treatment for
      acute gastric volvulus. Volvulus was primary in all the cases. Of the 8 patients,
      6 had organo-axial (75%) and 2 mesenterio-axial (25%) volvulus. Anterior
      gastropexy (gastrostomy) was performed in all the cases. There was no mortality
      and all the patients are doing well after one-year follow up.

PMID- 21888174
TI  - Immunosuppressive therapy in children.
AB  - The treatment of auto-immune diseases is evolving and newer agents become
      available. This review will outline treatment options in children with auto
      immune disorders. Treatment with current corticosteroids and azathioprine works
      in majority but issues of intolerance and incomplete response arise, which led to
      window of newer immunosuppressants including mycophenolate mofetil, cyclosporine,
      tacrolimus, sirolimus, and various antibodies of human and animal origin. The
      newer agents have been studied in fewer numbers of children, so they are not
      first-line treatment yet but do have a clear role in patients with intolerance or
      incomplete response to standard therapy.

PMID- 21888175
TI  - Anti-epileptic drug therapy: an overview of foetal effects.
AB  - Anti-epileptic drugs are associated with several foetal effects which necessitate
      a rational use of these drugs and early identification of the various adverse
      manifestations. This article gives a comprehensive review of foetal adverse
      effects described with various anti-epileptic drugs. The risk of malformations is
      increased 2-3 folds compared to general population, especially sodium valproate,
      more with polytherapy. The various manifestations of foetal anticonvulsant
      syndrome include developmental delay, malformations like facial clefts and neural
      tube defects, ocular abnormalities, learning difficulties, and digital
      hypoplasia. There is less data on effects of new anticonvulsant drugs, but they
      appear to be safer. The risk of teratogenicity is high with traditional drugs and
      with polytherapy; the newer agents like lamotrigine and oxcarbazepine are
      relatively safe. Individualisation of the drug therapy, optimisation of the dose
      and concurrent folic acid administration are important measures to reduce the
      potential risk to the foetus.

PMID- 21888176
TI  - Avian influenza: risk to human health and the need for an effective government
      policy.
AB  - Since 1997, outbreaks of highly pathogenic avian influenza have increased in
      frequency and severity. In December 2003, an outbreak of H5N1 avian influenza
      occurred in poultry in eight Asian countries. Vietnam and Thailand also reported
      human infection due to H5H1 avian influenza virus. Outbreaks of avian influenza
      (flu) among poultry continue and Thailand has reported human mortality in a
      second wave of human avian influenza in the year 2004. The main presenting
      features of avian influenza H5N1 in humans are fever, pneumonitis, lymphopenia
      and diarrhoea. Notably coryza, sore throat and conjunctivitis were absent. H5N1
      strains are sensitive to neuraminidase inhibitors which can be used for treatment
      and prophylaxis. India has been lucky so far, but with emerging infectious
      diseases, what can be predicted is that the unpredictable will happen and with a
      population exceeding one billion, the impact will be disastrous. The mortality
      rate of H5H1 avian influenza has been greater than 70% so far. The need of the
      hour is to have a proactive National Pandemic Influenza Respone and Preparedness
      Plan which should outline a coordinated national strategy to prepare for and
      respond to an influenza pandemic which is probably imminent. How prepared are we
      to handle it, is the question that all nations must ask themselves. This article
      summarises the current knowledge about this emerging infectious disease, the
      current global situation and the surveillance and diagnostic recommendations.

PMID- 21888177
TI  - Triplet pregnancy with partial hydatiform mole.
AB  - Triplet pregnancy with a coexisting mole is extremely rare. A 26 years old
      primigravida with multiple gestation and severe pre-eclampsia at 32 weeks
      gestation was brought to Sri Ramachandra University casualty. In view of abnormal
      Doppler study with discordant twins emergency lower segment caesarean section was
      done six days later. Part of the placenta showed molar changes. Histopathology
      confirmed partial mole. Patient received three cycles of methotrexate in view of
      rising titres of betahCG. Three months after delivery both babies are alive and
      well and betahCG for the mother became normal. This pregnancy continued beyond 32
      weeks gestational age with both babies being alive. Hence this case is being
      reported to highlight its rarity.

PMID- 21888178
TI  - Scalp abscess due to Salmonella typhimurium-- a case report.
AB  - The incidence of non-typhoidal salmonellosis has markedly increased in the past
      decade. Localised infection develops in approximately 5-10% of persons with
      salmonella bacteraemia. In this report, a 4-year-old female child suffering from
      acute lymphoid leukaemia is presented with high grade intermittent fever.
      Pustular lesions were observed over the right side of the scalp. The scalp
      abscess was drained and pus was sent for culture and sensitivity. Culture grew
      Salmonella typhimurium. Blood culture also grew the same organism. She had an
      uneventful recovery after treatment.

PMID- 21888179
TI  - Complete diphalia with renal agenesis.

PMID- 21888180
TI  - Evaluation of efficacy and tolerability of RB Tone forte tablet in the treatment
      of pregnancy anaemia.
AB  - In India < 90% of anaemia cases are estimated to be due to iron deficiency,
      because high iron requirements during pregnancy are not easily fulfilled by
      dietary intake. Ferrous ascorbate is widely prescribed iron salt in India but
      still no trial of ferrous ascorbate in Indian patients has been published. The
      study is to aim the evaluation of efficacy and tolerability of RB Tone forte
      tablet in the treatment of pregnancy anaemia. Fifty-five pregnant women (> 18
      years) with haemoglobin value between 8 and 11 g/dl in 13th week of pregnancy
      were included in the study. The duration of study was 6 months. Study drug RB
      Tone forte tablet, (Medley pharmaceutical, Mumbai) containing ferrous ascorbate
      equivalent to elemental iron 100 mg + folic acid 1.5 mg + elemental zinc 22.5 mg
      was prescribed once daily to all pregnant women from 13th week of pregnancy for a
      duration of 6 months. Haemoglobin was assessed at the beginning of the therapy
      and at the end of the trial. Study included birth weight and gestational age as
      outcomes because of a need for more information on the functional consequences of
      iron supplementation during pregnancy. Tolerability was evaluated based on the
      global assessment by the investigator and patients on a 3-point scale marked as
      excellent/good/poor. Fifty patients were included for final analysis, 5 patients
      lost to follow-up. Haemoglobin levels increased from the mean baseline value of
      8.950 +/- 0.1422 g/dl to 11.91 +/- 0.07840 g/dl, with mean increase of 2.964 +/-
      0.1624 g/dl at the end of trial (p < 0.0001). Mean birth weight of infants (n =
      50) was found to be 3079 +/- 25.10 g. Mean gestational age at the time of
      delivery was 38 weeks. No preterm delivery was reported, As per investigators
      assessment about tolerability of trial drug, 48% of patients reported good, 46%
      excellent and 6% reported poor tolerability. As per patient's assessment about
      tolerability 92% of patients reported good to excellent tolerability and 8%
      reported poor tolerability. All patients reported excellent gastro-intestinal
      tolerability of study drug. Positive effect on pregnancy outcome like gestational
      age and birth weight is mainly attributed to vasodilating property of ferrous
      ascorbate and beneficial effect of zinc. Ferrous ascorbate must be preferred as
      first choice of oral iron salt due to positive effect on haemoglobin value,
      vasodilating property and superior tolerability.

PMID- 21888182
TI  - We will make the difference.

PMID- 21888181
TI  - The efficacy and safety of amoxicillin-clavulanic acid 1000/125mg twice daily
      extended release (XR) tablet for the treatment of bacterial community-acquired
      pneumonia in adults.
AB  - This study was designed to demonstrate the efficacy and safety of
      pharmacokinetically enhanced amoxicillin/clavulanic acid 2000 mg/125 mg extended
      release formulation (ER), than conventional formulations against community
      acquired respiratory tract pathogens, particularly Streptococcus pneumoniae, with
      reduced susceptibility to amoxicillin. This is an open labelled, multicentric,
      prospective, interventional study carried out across India from June 2008 to
      March 2009. The study included adult patients (>18 years), weighing between 40 to
      60 kg with radiologically confirmed community-acquired pneumonia (CAP). Primary
      efficacy parameters were clinical response (fever, cough severity, sputum
      characteristics and improvement in dyspnoea grades) and laboratory parameters.
      Secondary efficacy parameters were radiological and bacteriological findings at
      the end of therapy. A total, 727 clinically and radiologically confirmed
      community-acquired pneumonia patients were enrolled in this study. Eighteen
      patients were lost to follow-up during study and 709 completed the study as per
      the study protocol. There was a significant improvement in clinical as well as
      laboratory parameters at the end of therapy. There was a significant improvement
      in fever, cough severity, sputum characteristic and dyspnoea grades from 101.88
      +/- 1.55, 2.18 +/- 0.76, 1.75 +/- 0.77 and 1.91 +/- 1.23 to 98.14 +/- 0.87 (p <
      0.0001), 0.24 +/- 0.45 (p < 0.0001), 0.14 +/- 0.39 (p < 0.0001) and 0.20 +/- 0.47
      (p < 0.0001) respectively. Laboratory parameters such as total WBC count and
      neutrophil percentage decreased significantly from 15317 +/- 662 and 80 +/- 9 to
      9067 +/- 558 (p < 0.0001) and 67 +/- 9 (p < 0.0001) respectively at the end of
      treatment. Bacteriological success and radiological success for amoxicillin
      clavulanate 1,000/62.5 mg at the end of treatment was 94.33% (150 of 159) and
      98.7% (700 of 709) respectively. Mild to moderate diarrhoea was reported in
      61/709 patients (8.6%). Amoxicillin-clavulanate 1,000/62.5 mg given twice daily
      for ten days was shown to be clinically effective and safe in the treatment of
      community-acquired pneumonia in adult patients. Therapy was well tolerated. [J
      Indian Med Assoc 2011; 109: 124-7]

PMID- 21888183
TI  - The dangerousness of schizophrenia.

PMID- 21888184
TI  - [Financial crisis and mental health in Greece].
AB  - Several studies indicate an association between economic crises and psychological
      burden. To investigate the possible impact of the current economic crisis on
      mental health in Greece, the association between two economic indicators
      (unemployment and average income) and mental health variables (psychiatric clinic
      admittance, visits to outpatients' departments and emergency units, suicides,
      homicides, mortality rates and divorces) was studied. The data were gathered by
      the Greek Statistical Service and some others were provided by the following
      hospitals: Eginition Hospital, Psychiatric Hospital of Attica, Athens General
      Hospital and Evaggelismos Hospital. Simple and multiple regression analyses were
      performed on the data. There was no significant correlation between the level of
      unemployment, as well as the average income, and admittance to the psychiatric
      clinics. A significant correlation was isolated between unemployment and visits
      to outpatients' department (R2 = 0.40, p = 0.001) and emergency unit (R2 = 0.49,
      p = 0.0002) of Eginition Hospital. The unemployment rate during the period 1981
      2008 was positively associated with the number of homicides (R2 = 0.16, beta =
      0.000049, p = 0.03), as well as the number of divorces (R2 = 0.20, beta = 0.005,
      p = 0.02) during the same period. The average income showed positive association
      with the visits to both outpatients' department (R2 = 0.55, p < 0.001) and
      emergency unit (R2 = 0,37, p = 0.004) of Eginition Hospital. However, the data
      from the 4 hospitals of the study revealed a negative correlation between average
      income and visits to outpatients' departments (R2 = 0.70, p = 0.02) and emergency
      units (R2 = 0.90, p < 0.001). Furthermore, a significant negative correlation
      between the average income and suicide rates (R2 = 0.37, p = 0.007), as well as a
      positive correlation between the average income and divorce rates (R2 = 0.73, p <
      0.001) were found. The findings show several similarities with previous surveys
      in countries with analogous economic crises, such as the Former Eastern Bloc
      countries, Asian countries and the USA. Future studies, at a more late stage of
      the economic crisis, are expected to reveal more reliable associations with
      mental health. Finally, these findings are expected to inform intervention
      programmes dealing with prevention or mitigation of the impact of economic crisis
      on citizens' mental health.

PMID- 21888185
TI  - [A volumetric study of brain structures in subtypes of depression].
AB  - The aim of this study is to compare the volumes of hippocampus, amygdala and
      subgenual prefrontal cortex among patients with melancholic depression, patients
      with psychotic depression and normal controls. Thirty nine patients with a
      diagnosis of major depression (22 with melancholic and 17 with psychotic subtype)
      and 18 normal controls were included in the study. Hippocampal, amygdala,
      anterior and posterior subgenual cortex volumes were measured by manual tracings
      on magnetic resonance volumetric images and compared across the 3 groups. We
      identified larger amygdala volumes and smaller left anterior subgenual cortex
      volumes in both patient groups compared to controls. There were no differences in
      hippocampal, right anterior and posterior subgenual cortex volumes across the 3
      groups. In conclusion, melancholic and psychotic depression were not
      differentiated regarding the volumes of the hippocampus, the amygdala, and
      anterior and posterior subgenual cortex, even though amygdala volumes and left
      anterior subgenual cortex volume of both patient groups were differentiated
      compared to controls.

PMID- 21888186
TI  - [Development of the Risk Assessment Suicidality Scale (RASS): a population-based
      study].
AB  - Suicide and suicide attempts are significant and costly public health problems.
      In order to prevent suicidal and other self-injurious behavior, research on the
      multiple factors involved in these behaviors with comprehensive and user-friendly
      instruments is necessary. The aim of the current study was to construct a self
      report instrument with emphasis on the items which describe suicide-related
      behavior itself rather than strongly related clinical features on the basis of a
      general population study. Twelve items comprising a new scale were applied to 734
      subjects from the general population (40.6% males and 59.4% females) aged 40.8 +/
      11.5, along with the STAI and the CES-D. The scoring method was developed on the
      basis of frequency table of responses to the individual scale items. The factor
      analysis returned 3 factors explaining 59.19% of total variance (Intention, Life,
      and History). The Cronbach's alpha was 0.85 for the Intention, 0.69 for the Life
      and 0.52 for the History subscale. The RASS is a reliable and valid instrument
      which might prove valuable in the assessment of suicidal risk in the general
      population as well as in mental patients.

PMID- 21888187
TI  - [Psychotherapeutic interventions in stereotypies].
AB  - Stereotypies belong to the psychomotor disorders and they are found in many
      different disorders. This article refers to the international literature about
      the psychotherapeutic interventions in stereotypies and reviews the
      psychotherapeutic techniques that are already being used for these disorders.
      This study refers to four kinds of psychotherapeutic treatment: (a) Behavioral
      therapy, (b) Milieu therapy which can be combined successfully with an
      occupational therapy, (c) Family therapy and (d) Supportive or cognitive or
      dynamic psychotherapy. The method used for finding the articles for this review
      was the web research. The articles found were 44 in total, but only 25 were
      studied extensively since they were absolutely relative to the subject of this
      review. 12 of these articles were case studies, 7 theoretical papers and 5 of
      them were reviews. The last one was a research epidemiological study. According
      to most of the articles, behavioral therapy is considered to be the most
      effective psychotherapeutic treatment for attenuating stereotypies and relies on
      techniques like systematic desensitization, environmental enrichment, positive
      reinforcement of alternative behaviors and negative reinforcement of the
      "problematic" behaviors. The milieu therapy, combined with occupational therapy,
      endeavours to shape an appropriate environment where the patient can recover.
      Family therapy focuses on fully informing the relatives about the nature of
      stereotypies. Supportive psychotherapy focuses on the current problems in the
      patient's life. The cognitive psychotherapy tries to fix the dysfunctional
      thoughts of the patients. Finally, the dynamic psychotherapy is focused on the
      restoration or reinforcement of the patient's defensive mechanisms. It should be
      noted that there is a lack of systematic research in the field of stereotypies in
      general and, especially, regarding psychotherapeutic interventions.

PMID- 21888188
TI  - [The clinical impairment of children with Attention Deficit Hyperactivity
      Disorder: problematic of diagnostic criteria].
AB  - One important consideration in the diagnosis of Attention Deficit Hyperactivity
      Disorder (ADHD), as set forth in the criterion D of DSM-IV, is the assessment of
      clinically significant impairment in social and academic functioning. Despite the
      avowed importance in the assessment of ADHD, there is little guidance in DSM-IV
      in defining impairment. Rating scales assessing impairment are few in number and
      rarely used in clinical practice. Overlooking impairment in diagnostic approaches
      has strong clinical implications, leading to false positive or false negative
      diagnoses. The relation between impairment and symptoms remains currently
      undefined and a controversial field in the ADHD literature, as many children can
      display the full range of ADHD symptoms without necessarily displaying
      significant impairment in their functioning. The relation between symptoms and
      impairment is more obvious in older children, where domains of impairment are
      more expanded. This finding suggests that symptoms and impairment are related,
      but yet there are distinct domains that should be measured independently to
      confirm the presence of ADHD. In conclusion, an operational definition of
      impairment, valid measures and diagnostic decision rules for incorporating
      impairment into the assessment of ADHD is warranted. Additional research is also
      needed to determine whether the age of onset of symptoms (before the age of
      seven) is different or should be separated from the age of onset of impairment.

PMID- 21888189
TI  - The impending demise of mortality abstracts.

PMID- 21888190
TI  - Whither mortality abstracts?

PMID- 21888191
TI  - Modeling total cholesterol as predictor of mortality: the low-cholesterol
      paradox.
AB  - Elevated total cholesterol is well-established as a risk factor for coronary
      artery disease and cardiovascular mortality. However, less attention is paid to
      the association between low cholesterol levels and mortality--the low cholesterol
      paradox. In this paper, restricted cubic splines (RCS) and complex survey
      methodology are used to show the low-cholesterol paradox is present in the
      laboratory, examination, and mortality follow-up data from the Third National
      Health and Nutrition Examination Survey (NHANES III). A series of Cox
      proportional hazard models, demonstrate that RCS are necessary to incorporate
      desired covariates while avoiding the use of categorical variables. Valid
      concerns regarding the accuracy of such predictive models are discussed. The one
      certain conclusion is that low cholesterol levels are markers for excess
      mortality, just as are high levels. Restricted cubic splines provide the
      necessary flexibility to demonstrate the U-shaped relationship between
      cholesterol and mortality without resorting to binning results. Cox PH models
      perform well at identifying associations between risk factors and outcomes of
      interest such as mortality. However, the predictions from such a model may not be
      as accurate as common statistics suggest and predictive models should be used
      with caution.

PMID- 21888192
TI  - PSA testing standards.

PMID- 21888193
TI  - Effect of increasing body weight on morbidity and mortality in South Korea.
AB  - The number of overweight and obese people in South Korea is increasing due to
      changes in exercise and dietary habits. The World Health Organization estimated
      that 45% of Korean men and 54% of women were overweight in 2005, and the
      percentages are expected to increase to 66% and 67%, respectively, by 2015.
      Studies have also found that more than 10% of Korean children and adolescents are
      now obese. These trends are important from both a public health and an insurance
      perspective because weight gain increases the likelihood of diabetes,
      cardiovascular disease, cancer, and other disorders that affect morbidity and
      mortality.

PMID- 21888194
TI  - Do I hear what you hear? Two cases and discussion.
AB  - It is fascinating to note the astute observations of clinicians almost a century
      ago. Familial hematuria was described in 1902 by Dr. Leonard Guthrie. Dr. Cecil
      Alport refined the disease description in 1927. (Both papers are still available
      online.) Applications for life insurance were recently received on two women who
      had Alport syndrome as a known diagnosis. The cases will be presented and used as
      a springboard to discuss Alport syndrome and benign familial hematuria (BFH).

PMID- 21888195
TI  - Q waves--does depth matter?
AB  - Deep narrow Q waves in an electrocardiogram may be significant and should suggest
      several possible diagnoses. By considering the leads where they are observed, the
      presence of additional ECG abnormalities, the applicant's age and any relevant
      clinical information, one can considerably narrow the diagnostic possibilities.

PMID- 21888196
TI  - Cryoglobulinemia.
AB  - Cryoglobulinemia indicates the presence of immunoglobulins that undergo
      reversible precipitation at low temperatures resulting in systemic inflammation
      and thrombosis producing variable clinical manifestations.

PMID- 21888197
TI  - Why do I do it and not publish it? Part 2.

PMID- 21888198
TI  - [Prenatal care attention in the view of a group of women who use the
      supplementary subsector].
AB  - This qualitative approach study, aimed at understanding the perception of women
      who went through the Prenatal Care Attention (PCA), on the context of the
      Supplementary Subsector (SS), in relation to the quality of this attention. Data
      were collected through semi-structured interviews and analyzed by descriptive
      categorization. For the interviews, the PCA was considered of good quality,
      meeting the women's needs and exzpectations. Receptivity, bonding with the expert
      the consequently transmitted safety feeling and the duration of the appointments
      were the prominent criteria in this evaluation. Their'experiences suggest that
      the PCA performed in the SS partially meets the recommendations of the Brazilian
      Ministry of Health (MH) and the World Health Organization (WHO). The
      appointments' frequency and the orientation provided also meet the
      recommendations. However, the data suggest that the PCA does not meet the
      orientations of the MH and the WHO regarding avoiding the extended use of hard
      technology, such as obstetric sonography.

PMID- 21888199
TI  - [Search by specialized training in occupational health nursing by nurses].
AB  - This article examines and discusses the search for specialized formation in
      Occupational Health Nursing for nurses. This is an exploratory descriptive
      qualitative study whose data were analyzed using content analysis. Data
      collection took place in May, 2010 with nine students from a specialization
      course that agreed to participate. All participants signed a free and informed
      consent term. The search for specialized formation is governed by the perspective
      for professional practice in Occupational Health Nursing and specificity of the
      curriculum in occupational health. Interfaces of the educational process confirm
      important contributions to a solid formation, projects nursing to
      theorical/academic levels and sets a path for the Stricto Sensu formation.
      Expectations, motivations and potentialities contributes to a contextualized
      governance of the educational process and the contemporary demands for
      Occupational Health Nursing.

PMID- 21888200
TI  - [Telephone counseling for young users of crack cocaine].
AB  - This study seeks to evaluate the use of Brief Motivational Intervention in a
      telephone counseling service offered to young people in the process of cessation
      of crack cocaine use. A descriptive study was conducted based on a survey of the
      records of callsfrom users during the period January 2006 to December 2007. The
      researchers included 40 recordsfrom calls of young people aged between 16 and 24
      years who consumed crack cocaine, associated or not with other substances. At the
      end of the six-month follow up, 65% of youths had stopped the consumption of
      crack cocaine. Of the total, 57.5% were in stage of preparation and action on the
      first call. The chances of relapse to crack cocaine use were higher in follow-ups
      to 30 days. The conclusion suggests that the association of IBM with telephone
      counseling is an important treatment option in cessation of crack cocaine use.

PMID- 21888201
TI  - [Pregnant teens: signs, symptoms, complications and presence of stress].
AB  - The objective of this work is to analyze the correlation between signs, symptoms
      and complications and the presence of stress in pregnant adolescents in health
      facilities in Maceio, Alagoas, Brazil. Quantitative, cross-sectional data were
      collected through questionnaire survey and tests of applied stress in adolescents
      treated in prenatal care. Data were analyzed by Epi Info version 3.5, using the
      odds as a statistical measure. The survey involved 140 pregnant girls, aged from
      10 to 19 years. Results show that 80.7% of them had some degree of stress, 57.1%
      being in the resistance phase and 18.6% at the stage of exhaustion. Statistical
      association was found between stress and some symptoms. The results indicate the
      presence of stress in adolescence and the need for special attention to the
      mental health of these women.

PMID- 21888203
TI  - [Health education: perceptions of professionals working in a Regional Health
      Office].
AB  - The aim of this study is to analyze the perceptions of professionals working in a
      Regional Health Office in Health Education. This is a qualitative exploratory
      descriptive study. Interviews were held with eight professionals from the state
      public sector, responsible for implementing public health policies. For analysis
      we used analyzing thematic content methodology. The results were discussed based
      on proposals of Paulo Freire. It was noted that health professionals have
      different perceptions regarding questions related to education and health
      education, and their educational practices are supported by the traditional
      system. The situation callsfor a change, which includes unifying concepts and
      building a new educational praxis, reviewing practices at all times and
      incorporating new knowledge to guide the construction of a new model of health.

PMID- 21888202
TI  - [Evaluation of organizational and performance features in a Basic Health Unit].
AB  - This research aims to evaluate organizational and performance features of a
      traditional Basic Health Unit, from the Primary Health Care service network, from
      users' perspective. The sample of 55 users was established using the same
      criteria of a rapid evaluation methodology, which was already validated and based
      on a free lectureship research sampling process. Empirical data were collected
      using the Primary Care Assessment Tool instrument validatedfor Brazil. Results
      revealed that access is one of the bottlenecks in the system. Primary Health Care
      practice does not focus on families and community in its process of work. The
      Basic Health Unit offers several services, establishing itself as an entrance to
      the system, though it does not always establish a link with users. Investments
      are needed in the Brazilian municipal health network in order to strengthen
      Primary Health Care attributes.

PMID- 21888204
TI  - [Stress in nurses at a hemodynamics ward in Rio Grande do Sul, Brazil].
AB  - This study aimed to evaluate the relationship between stress and symptoms
      reported by nurses working in units hemodynamics. Data were collected through a
      questionnaire. For analysis, the results were considered statistically
      significant if p < 0.05, with an interval of 95% confidence. The population
      consisted of 63 nurses with a predominance of females (90.5%) and average age of
      35.24 (+/- 8.21) years. Most participants werepostgraduate (77.8%) and did not
      have another job (77.8%). In relation to stress, 52.4% of nurses had an average
      between 1.11 and 1.97, classified as medium stress, and the critical situations
      domain presented the highest score (1.63 +/- 0.29). Regarding symptoms, the
      domain skeletal muscle had a higher average (1.39 +/- 0.94). In this study, there
      was high significant positive correlation between stress and symptoms (r = 0.629,
      p < 0.001), thus it is concluded that stress is directly related to the
      symptomspresented by the nurses.

PMID- 21888205
TI  - [Family in the waiting room of an intensive care unit revealed feelings].
AB  - This is a qualitative study that aims to understand the feelings of relatives of
      patients admitted to the Intensive Care Unit (ICU). The study was conducted in
      the ICU of a large general hospital in the western region of Santa Catarina. The
      data collection occurred in 2009 with a semi structured interview to eighteen
      families. For data treatment the collective subject discourse was used. Reports
      emerged of two items related to feelings: hospitalization in the ICU and while
      waiting to enter the unit. The analysis revealed feelings as pain, anguish,
      sadness, helplessness,fear, despair, anxiety and expectation infinite. It is
      hoped that these results may assist in the training of professionals, to host the
      family and its insertion in the ICU environment as an element to be integrated
      into nursing care, through actions welcoming, helping them to cope with
      hospitalization of a relative in a critical unit.

PMID- 21888206
TI  - [Factors associated with delay in children development, Rio Grande, Rio Grande do
      Sul, Brazil].
AB  - This analytical study aims to evaluate the factors associated to developmental
      delay in 8-12 months aged children, indicated as at risk at birth in Rio Grande,
      Rio Grande do Sul Brazil. The instruments used were the Denver Development
      Screening Test II, anthropometric evaluation and questionnaires. Two hundred and
      twenty children (both at risk and out of risk) participated. It was found a
      prevalence of o20.5% of potential delay in psychomotor development. Children who
      presented a risk of a suspicious DDST II were part of lower income families;
      their mothers had not been to more than six prenatal visits; and had
      inappropriate weight-age indicator The data suggest the need of a rethinking of
      policies on child health, given that other criteria could be included in the risk
      conditions to the child at birth.

PMID- 21888207
TI  - [Risk factors for low birth weight in public maternities: a cross-sectional
      study].
AB  - Low birth weight is considered the most influentialfactor in determining neonatal
      morbidity and mortality. Also it may be associated with low levels of
      socioeconomic development and maternal and child care. This quantitative research
      aims to describe the risk factors for low birth weight newborns in public
      hospitals in the city of Santa Maria, Rio Grande do Sul Brazil. Quantitative data
      were analyzed using descriptive statistics. The results suggest the main risk
      factors are: the preterm birth,family income below - two minimum salaries,
      nulliparity and multiparity, the occurrence of previous abortion, surgery
      delivery, infections, pre-eclampsia and a history of other children of low
      weight. It is recommended to invest in the quality of prenatal care, since many
      of these risk factors can be avoided or minimized by prenatal care quality.

PMID- 21888208
TI  - [Identification and analysis of errors in the preparation of drugs in a pediatric
      hospital unit].
AB  - This study aims to identify and analyze errors in the preparation of medicines in
      the pediatric unit of a hospital. This descriptive study was performed withfour
      professionals responsible for the preparation of medicines developed in a
      hospital in the interior of Minas Gerais, Brazi. They were submitted to the
      technique of structural observation and formulary. A descriptive analysis of the
      data was performed. The results highlight the lack of guidelines for the
      preparation of drugs, presence of interruptions during theprocess, failure in the
      utilization of recommended hand washing techniques and disinfection of bottles
      and vials. It is necessary to make professionals aware of the occurrence and
      consequences of the main mistakes made by the team, as a stimulus for prevention
      through safe and effective practices to improve the quality of care.

PMID- 21888210
TI  - [Sexual orientation in the school environment: fact or eagerness?].
AB  - This qualitative research aims to analyze how sexual orientation has been
      incorporated into pedagogic practices through the point of view of educators from
      public schools of fundamental teaching. Twenty three educators from Cajazeiras,
      Paralba, Brazil participated in the study. The focus group was elected as
      technique of investigation, and the empirical data obtained were organized
      according to the technique of analysis of content. It was realized that there is
      an effort of the actors to privilege contents related to sexual orientation in
      the school environment though they demand that a level of informative and
      subjective character about the "sexuality" be encouraged providing the educators
      with a space for re-significations of its internality of values. The information
      directed to self-care must transcend the limits of prevention and hygienisation,
      incorporating extensive, inclusive and reflective methodologies, which recognize
      human and social rights and promote the ethical construction of citizenship.

PMID- 21888209
TI  - [Civil construction workers and preventive measures against skin cancer: nursing
      contribution].
AB  - Civil construction's workers are one of the most risk groups to the occupational
      cancer. The purpose was to identify these workers knowledge about skin cancer and
      describe protection/prevention measures adopted by them. This is a descriptive
      and qualitative nature research, developed with 50 workers of a great load
      building site firm at municipal district of Rio de Janeiro, Brazil. Data was
      collected through a form. From descriptive and statistical analysis, the results
      showed that the protection measures adopted by workers to avoid skin cancer are
      insufficient; moreover, they are not used in an aligned way with the literature.
      The most important necessary change relates to ife styles and access to
      information and knowledge about skin cancer. Thus, nursing's interventions along
      the Worker's Health stuff can contribute to the implementation of preventive
      measures against occupational cancer.

PMID- 21888211
TI  - [Principles of the Unified Health System nurses' conception of the Family Health
      Strategy].
AB  - The study aims to examine nurses' understanding of the principles of the Unified
      Health System. universality, equity and integrality. This is a descriptive study
      conducted from August to September, 2008, through semi-structured interviews with
      26 nurses of the basic units of Health fom Fortaleza, Ceara, Brazil The technique
      o f content analysis was used toorganize the data. The results show that nurses
      perceive universality as a universal access for all users of health services;
      equity as an equal attendance of the population, guaranteeing special attention
      to the poor; and integrality of care as the provision of services at all three
      levels of care. The conclusion shows that the practitioners' conception of these
      principles are similar to those presented in the Federal Constitution. This
      represents an important element for the implementation and strengthening of the
      model of health care in Brazil.

PMID- 21888212
TI  - [Promotion in mental health, nursing creating and intervening with children's
      stories].
AB  - This paper refers to the importance of the childish stories as an instrument for
      the nursing action and the mental health promotion in childhood. The objective
      was to veriyj the recognition of the children's emotions, through stories
      specific to health. This is a descriptive-exploratory study of a qualitative
      nature, conducted in seven groups meetings with six children aged seven to ten
      years in an outpatient childish mental health. In the data collection the
      following were used as instruments: six fairy tales, the play of emotions,
      emotional faces, drawings, paintings and clay sculptures. Thematic analysis was
      used in which the following emerged, the recognition of emotions. The children
      recognized four basics emotions: sadness, joy, fear and anger. It was found in
      the study that the creation of contextualized stories and the strategy of
      storytelling group may be useful as a tool for research and qualification of
      nursing actions, to promote children's mental health.

PMID- 21888213
TI  - [Reactions and feelings of nursing professionals facing their patients' death].
AB  - This study aims to know the reactions and feelings of nursing professionals
      facing their patients' death. This qualitative research was developed at the
      Medical Clinic Unit of a university hospital in Southern Brazil. The population
      of the study was composed of four nurses and five nursing technicians that work
      at this unit. Data were collected in the second semester of 2006 through semi
      structured interviews and analyzed with the use of thematic analysis. The
      analysisproduced three categories reactions of nursing professionals facing death
      in daily work, feelings towards facing death in daily work; and nursing team
      members facing the care of the body after death. Results indicate that there is a
      need for discussing this issue in the workplace in order to prepare these
      healthcare workers to deal with their patients' death.

PMID- 21888214
TI  - [Mental health in primary care: an assistant research approach].
AB  - This study aims to comprehend the expectations and aspirations of a community
      about the deployment of a group of mental health in primary care. This is a
      qualitative study that uses the assistant convergent research approach. Data were
      collected through workshops with psychotropics users, accompanied by Primary Care
      in the South of Brazil. The first workshop aimed to reflect on and develop
      strategies to dealing with asylum model. The second discussed the importance of
      spaces that strengthen bonds of affection and act as means of prevention in
      mental health. The third discussed the issue of restriction of liberty imposed by
      mental suffering. It was found that spaces dedicated to mental health in the
      primary care will add to the effectiveness of the practices and to the
      construction of new knowledge to the user's health and life

PMID- 21888215
TI  - [Pressure ulcers in the elderly: analysis of prevalence and risk factors].
AB  - Studies on the prevalence of pressure ulcer and e.rperiences of living with
      elderly people with injuries during practice in long-stay institutions for the
      elderly have given rise to many concerns. This work aims to examine the
      prevalence and risk factors of pressure ulcer in the institutionalized elderly.
      This retrospective, quantitative study was held in a public long-stay institution
      for the elderly in Fortaleza, Ceara, Brazil. The sample consisted of 300 medical
      records of elderly from 2006 to 9009. It was used for data collection form. All
      ethical guidelines were followed. The most prevalent risk factors were: stroke
      (60%) and hypertension (74.3%). The average prevalence of pressure ulcers in the
      period was 18.8%, rangingfrom 11.1% to 23.2%. The recommendations for the
      prevention of pressure ulcers include the development of a prevention program to
      promote active aging

PMID- 21888216
TI  - [A touch on masculinity: prostate cancer prevention in traditionalist Gauchos].
AB  - This cross-sectional and quantitative study was carried out with 88
      traditionalist gauchos, who took part in the Farroupilha Camp in 2009. It
      verified their adherence to prostate cancer examination, also analyzing which
      variables influence in the adherence to digital rectal examination. Participants
      had an average age of 58.5 years, with high income and schooling level. Most
      (92%) lived longer in urban areas, had healthfollow-up at private health services
      (70.5%) and have had some preventive examination for prostate cancer (83%). The
      ones who had preventive examination had higher education, income and access to
      private health services. There was lower demand for preventive exams by those who
      lived most of their lives in the rural area. However, there was no relationship
      between the place where participants lived longer and adherence to digital
      rectalexamination. Findings indicate correspondence in the adherence to
      preventive examinations with other studies carried out in Brazil.

PMID- 21888217
TI  - [Postpartum depression screening scales: a systematic review].
AB  - This study aims to conduct a systematic review of postpartum depression (PPD)
      screening scales in puerperal applied until 16 weeks after delivery among women
      above 15 years old. Articles were searched in 4 databases. The included articles
      should describe precisely the definition and the validation of the used
      instruments. Out of the 424 abstracts found, 62 complete articles were accessed
      and only 18 articles that fulfilled the above-mentioned requirements were
      included. PPD screening period varied from 2 to 10 days postpartum, and patients
      were retested between 8 to 16 weeks postpartum. PPD was diagnosed in 8.8 to 40%
      of the patients sampled in those studies. The most frequent used scale was the
      Edinburgh Postpartum Depression Scale (EPDS). It was concluded that scales are
      frequently used in research studies, and may allow the identification of PPD in
      gestating and puerperal patient care.

PMID- 21888218
TI  - [Nursing classification systems and their application in care: an integrative
      literature review].
AB  - This study sought for scientific evidences on the use of nursing classification
      systems in care through an integrative literature review. The following databases
      were used LILACS and PubMed. The keywords used were classification, nursing,
      standardized language, system. Thirty-eight articles were selected. Five major
      classification systems, implemented in the services, were found: nursing
      diagnosis (North American Nursing Diagnosis Association International), nursing
      interventions (Nursing Interventions Classification), nursing outcomes (Nursing
      Outcomes Classification), the International Classificationfor Nursing Practice
      and the International Classificationfor NursingPractice in Colletive Health. The
      articles covered aspects related to implementation, assessment continuing
      education and validation of terms related to classification systems. The use of
      nursing classification systems provides benefits for care, improving it, the
      quality of information and service organization.

PMID- 21888219
TI  - [Nursing technologies to promote breastfteeding: integrative literature review].
AB  - This paper aims to accomplish an integrative literature review on the types of
      technologies that nurses have developed or that they could use to promote
      breasfeeding. The research was carried out in October 2009 using the descriptors:
      breasfeeding, nursing and technology, in the CINAHL, Scopus, PubMed and LILACS
      databases. 127 references were founda 10 of them participated in the analysis
      since they fit the study selection criteria. It was verified that most (6 - 60%)
      of the studies were found in Pubmed in English (8 - 80%) and didn't mention the
      study type (4 - 40%). Thirteen types of care technologies were identified
      classified as hard (8 - 61.5%) and soft (5 - 38.5%); the main target audience was
      formed by children's mothers (9 - 90%), and the video/footage was the most used
      technology (4 - 40%). The use of soft and sof-hard technologies should be
      stimulated,for they are considered practical and easy to be developed and
      applied.

PMID- 21888220
TI  - [Possible contributions of acupuncture in the teaching of clinical simulation in
      nursing].
AB  - This study situates the emerging discussion about the possibility of integration
      of knowledge from acupuncture as a contribution to the pedagogicalpractices of
      simulated clinical education of undergraduate nursing education. The reflective
      work emerged as an approach to the dissertation project "Study on the evaluation
      of trigger learning simulation - Morphofunctional Lab/College of
      Nursing/Universidade Federal de Pelotas". The integral relationship between man
      and nature developed in acupuncture emerges as a suggestion of discussions and a
      potential pedagogical toolfor the clinical simulation in nursing. In this
      reflection, results prove that there is a need to develop this educational
      resource aimed at expanding the teaching of clinical simulation in nursing.

PMID- 21888221
TI  - [Nursing care in the perspective of an expanded clinic in the Intensive Care
      Unit].
AB  - This article aims to reflect on nursing care in view of the expanded clinic in
      the Intensive Care Unit (ICU). The expansion of the clinic aims to think of human
      beings considering their biological aspects and subjectivity, which is viewed in
      the light of each particular case through an integral approach, interdisciplinary
      and shared. Joint efforts by interdisciplinary teams are necessary to modify the
      ICU setting, where the hegemonic model is historically perpetuated.
      Responsibility with the individual their welfare and environment is part of
      praxis, a fact that enable a change in hegemonic practicefor extended clinic.

PMID- 21888222
TI  - [Sickle-cell disease: short communication on how children express through games
      what it means for them to have the disease].
AB  - Brief notice of a study aimed at understanding the significance of sickle cell
      anemia in children between 3 and 12 years old. This qualitative research is
      grounded in Symbolic Interactionism as a theoretical perspective, and in Grounded
      Theory as a research method. The data have been collected through interviews with
      children, with the use of therapeutic play sessions. Preliminary data analysis
      has allowed us to understand that sickle cell anemia is a sad experience for
      children, because that more than experiencing pain, children realize they are
      powerless in relation to the suffering; they recognize its symptoms, understand
      the need for treatment, and consider it only as palliative. Children also
      consider their family as an important support, and have the hospital as
      reference.

PMID- 21888223
TI  - Instantaneous and historical temperature effects on alpha-pinene emissions in
      Pinus halepensis and Quercus ilex.
AB  - We compared the role of instantaneous temperature and temperature history in the
      determination of alpha-pinene emissions in Mediterranean conifer Pinus halepensis
      that stores monoterpenes in resin ducts, and in Mediterranean broad-leaved
      evergreen Quercus ilex that lacks such specialized storage structures. In both
      species, alpha-pinene emission rates (E) exhibited a significant exponential
      correlation with leaf temperature and the rates of photosynthetic electron
      transport (Jco2+o2) started to decrease after an optimum at approximately 35
      degrees C. However, there was a higher dependence of E on mean temperature of
      previous days than on mean temperature of current day for P. halepensis but not
      for Q. ilex. Jco2+o2 showed a maximum relationship to mean temperature of
      previous 3 and 5 days for P. halepensis and Q. ilex respectively. We conclude
      that although the best correlation of emission rates were found for instantaneous
      foliar temperatures, the effect of accumulated previous temperature conditions
      should also be considered in models of monoterpene emission, especially for
      terpene (see text) species.

PMID- 21888224
TI  - Inhibitory effect of antioxidants on the benz[a]anthracene-induced oxidative DNA
      damage in lymphocyte.
AB  - Benz[a]anthracene is a ubiquitous environmental contaminant formed during the
      incomplete combustion of organic material. Some of the metabolites of
      benz[a]anthracene are known to be toxic and carcinogenic. In this investigation,
      benz[a]anthracene-induced oxidative damage to lymphocyte DNA was evaluated with
      the Comet assay (single cell gel electrophoresis). The level of oxidative DNA
      damage caused by benz[a]anthracene increased in a dose-dependent manner (24, 49)
      and oxidative DNA damage was significantly inhibited by 5 and 10 microg ml(-1)
      ascorbate, 5 microg ml(-1) polyphenols, as well as 5 and 10 microg ml(-1)
      curcumin. Moreover, traditional Korean medicinal herbs such as Acanthopanax and
      ginseng significantly reduced DNA damage. The results demonstrate that
      antioxidant supplementation to lymphocytes inhibits oxidative DNA damage in
      vitro, supporting an inhibitory effect against oxidative DNA damage, probably due
      to reduction of reactive oxygen species production induced by benz[a]anthracene.

PMID- 21888225
TI  - Statistical tools for analysing the data obtained from repeated dose toxicity
      studies with rodents: a comparison of the statistical tools used in Japan with
      that of used in other countries.
AB  - In the present study, an attempt was made to compare the statistical tools used
      for analysing the data of repeated dose toxicity studies with rodents conducted
      in 45 countries, with that of Japan. The study revealed that there was no
      congruence among the countries in the use of statistical tools for analysing the
      data obtained from the above studies. For example, to analyse the data obtained
      from repeated dose toxicity studies with rodents, Scheffe's multiple range and
      Dunnett type (joint type Dunnett) tests are commonly used in Japan, but in other
      countries use of these statistical tools is not so common. However, statistical
      techniques used for testing the above data for homogeneity of variance and inter
      group comparisons do not differ much between Japan and other countries. In Japan,
      the data are generally not tested for normality and the same is true with the
      most of the countries investigated. In the present investigation, out of 127
      studies examined, data of only 6 studies were analysed for both homogeneity of
      variance and normal distribution. For examining homogeneity of variance, we
      propose Levene's test, since the commonly used Bartlett's test may show
      heterogeneity in variance in all the groups, if a slight heterogeneity in
      variance is seen any one of the groups. We suggest the data may be examined for
      both homogeneity of variance and normal distribution. For the data of the groups
      that do not show heterogeneity of variance, to find the significant difference
      among the groups, we recommend Dunnett's test, and for those show heterogeneity
      of variance, we recommend Steel's test.

PMID- 21888226
TI  - Effect of butyl benzyl phthalate on life table-demography of two successive
      generations of cladoceran Moina macrocopa Straus.
AB  - In this study, the acute toxicity of butyl benzyl phthalate (BBP) to freshwater
      cladoceran Moina macrocopa was tested, and its chronic effects on survival and
      reproduction of two successive generations of the cladoceran were studied using
      life-table demographic method. The results showed that the 48-hr LC50 of BBP for
      M. macrocopa was 3.69 mg l(-1). Compared to the blank controls, BBP at 125, 500,
      1000 and 2000 microg l(-1) significantly shortened the life expectancy at birth,
      BBP at 125-2000 microg l(-1) decreased the net reproductive rate, and BBP at 500
      and 1000 microg I(-1) shortened the generation time but increased the intrinsic
      rate of population increase of the parental M. macrocopa. BBP at 62.5,125,
      500,1000 and 2000 microg l(-1) increased the intrinsic rate of population
      increase of the F1 generation. A significant dose-effect relationship existed
      between BBP concentration and life expectancy at birth, net reproductive rate as
      well as intrinsic rate of population increase of the parental M. macrocopa. The
      parental M. macrocopa were more sensitive in survival, development and
      reproduction to BBP than the F1 generation, but the reverse was also true in the
      population growth. Extending chronic toxicity tests to the second generation of
      M. macrocopa increased the cost-effectiveness of the assays.

PMID- 21888227
TI  - In-vitro antimicrobial activity and synergistic/antagonistic effect of
      interactions between antibiotics and some spice essential oils.
AB  - Spices and herbs have been used for many years by different cultures. The aim of
      the present study is (1) to investigate in-vitro antimicrobial effects of
      different spices and herbs (5 species: Rosmarinus officinalis (Rosemary),
      Coriandrum sativum (coriander), Micromeria fruticosa (L.) Druce subsp.
      Brachycalyx P.H. Davis (White micromeria), Cumium cyminum (cumin), Mentha
      piperita (Peppermint) against different bacteria and fungi species, and (2) to
      discuss the in-vitro possible effects between the plants and antibiotics. The
      microorganisms used were Micrococcus luteus LA 2971, Bacillus megaterium NRS,
      Bacillus brevis FMC 3, Enterococcus faecalis ATCC 15753, Pseudomonas pyocyaneus
      DC 127, Mycobacterium smegmatis CCM 2067, Escherichia coil DM, Aeromonas
      hydrophila ATCC 7966, Yersinia enterocolitica AU 19, Staphylococcus aureus Cowan
      1, Streptococcus faecalis DC 74 bacteria, and Saccharomyces cerevisiae WET 136,
      Kluvyeromyces fragilis DC 98 fungi in this study. The results indicated that
      essential oils of Rosmarinus officinalis, Coriandrum sativum L., Micromeria
      fruticosa (L.) Druce subsp. brachycalyx P.H. Davis, Cumium cyminum L., Mentha
      piperita L. were shown antimicrobial activity in the range of 7-60 mm 2 microl(
      1) inhibition zone to the microorganisms tested, using disc diffusion method.
      Standard antibiotic such as Gentamicin (10 microg), Cephalothin (30 microg),
      Ceftriaxone (10 microg), Nystatin (10 U) discs were used for comparison with the
      antimicrobial activities of essential oils of these plants. In addition,
      antibacterial activity of essential oils of these plants was researched by
      effects when it was used together with these standard antibiotics in vitro.
      However, antibacterial activity changed also by in vitro interactions between
      these standard antibiotics and essential oils of these plants. Synergic, additive
      or antagonist effects were observed in antibacterial activity.

PMID- 21888228
TI  - Utilization of lipids during aestivation of the African lungfish, Protopterus
      annectens.
AB  - Sequential alterations of body weights as well as total lipids, triglycerides,
      cholesterol and ketone body levels in the blood of Protopterus annectens during
      twelve month duration of aestivation were investigated. The results revealed that
      after the first trimester of dormancy, there was significant body weight
      reduction (p < 0.05) coupled with significant hypolipodaemia, hypotriacylgly
      cerolaemia and hypocholesterolaemia respectively (p < 0.05) but without
      significant ketonaemia (p < 0.05). The total lipid, triglyceride, cholesterol and
      body weight reductions continued through the second, third and fourth trimesters
      of aestivation respectively (p < 0.05) but with serum ketone body levels
      remaining unaltered (p < 0.05). Thus, the utilization of lipids as a source of
      energy during aestivation of P. annectens does not lead to ketone body
      accumulation.

PMID- 21888229
TI  - Histopathological alterations in hepatopancreas of Gafrarium divaricatum exposed
      to xylene, benzene and gear oil-WSF.
AB  - Gafrarium divaricatum were exposed to xylene (4.25 and 8.50 mg l(-1)), benzene
      (4.35 and 8.70 mg l(-1)) and gear oil-WSF (1 and 2%) for 30 days. Chronic
      exposure of clams to the pollutants resulted in loss of bubbling epithelium,
      reduction in cytoplasm volume and density, fusion of cell membranes and nuclei
      forming darkly stained area at basal part of the cells. Disintegration of
      basement membrane due to damaged epithelial cells, disruption of inner lining of
      tubule, formation of necrotic spaces, separation of epithelial cells from
      basement membrane, increase in internal luminar area, complete necrosis of
      epithelial cells as well as occurrence of cell debris in between the tissue were
      also observed in the clams due to chronic exposure of the toxicants.

PMID- 21888230
TI  - Studies on oxidative stress induced nerve conduction deficits in cigarette
      smokers.
AB  - An important role of oxidative stress for the development of vascular and
      neurological complications has encouraged us to undertake a study to assess the
      oxidative stress induced nerve conduction deficits among cigarette smokers.
      Eighteen regular male cigarette smokers and twenty nine male non-smokers were
      diagnosed for clinical neuro-physiological tests viz., motor and sensory nerve
      conduction velocity (MNCV and SNCV) and redox status. Significant depletion of
      reduced glutathione (GSH) level (p < 0.05) and significant increase in
      malondialdehyde (MDA) level (p < 0.01) was found in smokers compared to non
      smokers. Motor and sensory nerve conduction velocity showed no significant
      difference among smokers compared to non-smokers. The present study shows that
      smoking can induce oxidative stress among smokers but could not exacerbate to
      nerve conduction deficits.

PMID- 21888231
TI  - Survey of nitrogen use pattern in rice in the irrigated rice-wheat cropping
      system of Haryana, India.
AB  - Seeing the sustainability of rice-wheat cropping system (RWCS) of the Indo
      Gangetic Plain, adequate crop nutrition in general and nitrogen (N) in particular
      holds the key to sound crop management. The excessive application or insufficient
      management of N means an economic loss to the farmer and may lead to yield
      penalties and environmental problems. Improving N management in consonance with
      other nutrients is much important to break yield plateaus as breeding for high
      yielding is not happening in recent years. Findings from farm survey are used to
      evaluate the on-farm N management practices in rice crop of the study area. The
      crop management practices (especially time of sowing/transplanting and irrigation
      requirement) and resource base of the farmers decided the N use pattern of the
      farmers. The N(Physical optimum) and N(economic optimum) exceeding the
      recommended levels revealed the apparent need for the revalidation of the
      existing recommendations. Paddy yield increased significantly within different
      rice types. This study generated comprehensive data on N use pattern in rice in
      the study area.

PMID- 21888232
TI  - Screening and detection of biomarkers in chickpea plants exposed to chromium and
      cadmium.
AB  - A broad screening protocol, covering the most general phytochemical groups of
      compounds, was developed on the basis of high performance thin layer
      chromatography (HPTLC). A total of six TLC systems, comprising three
      derivatization reagents, two stationary phases and two mobile phases, were
      included. The screening method was applied for the identification of biomarkers
      in the chickpea plant exposed to cadmium and chromium. The biomarkers were
      selected on the basis of significant changes (0.26-4.6 fold) in concentration
      levels of phytochemicals. Totally, five different amino acids, three organic
      acids, one sulphur containing compound and one sugar were identified as
      biomarkers in chickpea exposed heavy metal.

PMID- 21888233
TI  - Role of bioinoculants and organic fertilizers in fodder production and quality of
      leguminous tree species.
AB  - The comparative effect of dual inoculation of native N fixer (Rhizobium) and AM
      fungi consortia with different organic fertilizers (vermicompost and farm yard
      manure) on fodder production and quality of two leguminous tree species (Leucaena
      leucocephala (Lam) de. Wit. and Sesbania sesban (L.) Merr.) in silvopastoral
      system and their impact on the fodder production of un-inoculated Panicum maximum
      Jacq. under cut and carry system. After three years of plantation maximum tree
      survival was in L. leucocephala in all the treatments in comparison to S. sesban
      while fodder production was more in S. sesban for initial two years and in third
      year it accelerated in L. leucocephala. Dual inoculation with vermicompost
      significantly improved fodder production, fodder quality and rhizosphere
      microflora in L. leucocephala but in S. sesban dual inoculation was at par with
      single inoculation of N fixer, AM fungi and control (without inoculation). The
      grass production was higher with L. leucocephala for two years while in third
      year it was more with S. sesban. The association of Rhizobium with AM fungi in L.
      leucocephala was better than in S. sesban.

PMID- 21888234
TI  - Distribution of diatom Pseudo-nitzschia and dinoflagellates of Dinophysis spp
      along coast off Goa.
AB  - As a part of an annual analysis on the phytoplankton distribution and
      composition, regular monthly sampling carried out during October 2007- September
      2008 from salinity gradient zones in the intertidal waters along the coast of
      Goa. Among the 179 species of phytoplankton observed during this study, as many
      as 11 of them are recognized, potentially toxic ones. The toxic diatom species,
      Pseudo-nitzschia pungens was quite preponderant, in particular during the pre
      monsoon month of May 2008 off Chapora, a perennially low salinity location. Among
      the 10 toxic dinoflagellate species detected, the known toxic species,
      Alexandrium minutum followed by Dinophysis acuminata were found to attain maximum
      cell numbers in the study area. It is apparent from our results that the toxic
      species do occur in all salinity zones sampled and during many months of the year
      in coastal waters off Goa. Though directly governed by the variations in nutrient
      concentrations, some of these toxic phytoplankton species attain high cell
      numbers. It is reasonable for us to therefore caution that the toxic species do
      prevail in these waters.

PMID- 21888235
TI  - Comparative larvicidal potential of different plant parts of Withania somnifera
      against vector mosquitoes in the semi-arid region of Rajasthan.
AB  - Larvicidal potential of the extracts from different parts viz. green and red
      fruits, seeds, fruit without seeds, leaves and roots of Withania somnifera in
      different solvents was evaluated against larvae of Anopheles stephensi, Aedes
      aegypti and Culex quinquefasciatus, the important disease vectors prevalent in
      the semi-arid region. Experiments were carried out on late 3rd or early 4th
      instar larvae of these mosquitoes using standard WHO technique. 24 and 48 hr LC50
      values along with their 95% confidence limits, regression equation, chi-square
      (chi2)/heterogeneity of the response have been determined by log probit
      regression analysis. The 24 hr LC50 values as observed for whole green fruits in
      water, methanol and petroleum ether were 350.9, 372.4, 576.9; 115.0, 197.1,
      554.6; 154.9, 312.0, 1085.0 while corresponding values for red fruits were 473.5,
      406.4,445.2; 94.7, 94.5, 1013.0; 241.8, 535.0, 893.3 mg l(-1) for An. stephensi,
      Ae. aegypti and Cx. quinquefasciatus respectively showing that methanol extracts
      were more effective against anophelines as compared to culicines when whole
      fruits were taken. The 24 hr LC50 values as observed for seeds in acetone,
      methanol and petroleum ether were 188.1, 777.5, 822.5; 245.5, 769.0, 1169.0;
      140.3, 822.9, 778.4 and for fruit without seeds were 80.2, 97.6, 146.6; 88.4,
      404.4, 1030.0; 30.0, 44.5, 54.2 mg l(-1) for the above mosquito species
      respectively showing that extract of fruit without seeds were most effective in
      petroleum ether followed by acetone and methanol extracts. However, experiments
      conducted with methanol extracts of leaves and roots of this plant species did
      not show any appreciable larvicidal activity and a 20-40% mortality was observed
      up to 500 mg l(-1) of the extracts. Overall larvae of anophelines were found more
      susceptible as compared to culicines to all the extracts tested. Petroleum ether
      extract of fruit without seeds was found most effective against all the mosquito
      species showing that active ingredient might be present in this part of the plant
      species. The study would be of great importance while planning vector control
      strategy based on alternative plant derived insecticides.

PMID- 21888236
TI  - Community composition of aquatic birds in lakes of Bangalore, India.
AB  - Observations were made on the occurrence, abundance, richness, and diversity of
      waterbirds in 15 major lakes in Bangalore city during 2008 - 2009. During the
      study period 35 species of aquatic birds were recorded. The number of aquatic
      bird species recorded at various lakes ranged from 23 to 35. The percent
      abundance of waterbirds recorded in the study lakes ranged from 2.46 to 21.49 and
      itwas significantly different (p < 0.05). The diversity and species evenness of
      waterbirds in the lakes ranged from 2.07 to 3.16 and 0.32 to 0.76, respectively.
      There was a significant difference (p < 0.05) in the diversity and species
      evenness of waterbirds among different lakes. Species richness of the bird
      population ranged from 2.89 to 4.01 in the different study lakes and it was not
      significantly different (p > 0.05). There was a variation in number of waterbird
      species recorded during summer, monsoon and winter seasons. Of the 35 waterbird
      species, Bubulcus ibis showed cent percent frequency, whereas less frequently
      (4.44%) observed species was Anas platyrhynchos. Among various waterbird species,
      Bubulcus ibis, Fulica atra, Tringa hypoleucos, Motacilla maderaspatensis,
      Phalacrocorax niger Egretta garzetta, Charadrius dubius, Ardeola grayji, Halcyon
      smymensis and Motacilla alba were frequently encountered in most of the study
      lakes.

PMID- 21888237
TI  - Study of fluoride content in groundwater of Nawa Tehsil in Nagaur, Rajasthan.
AB  - There is a severe fluoride problem in Nawa tehsil of Nagaur district. Villagers
      are suffering from dental fluorosis and skeletal fluorosis. So an extensive
      geochemical study of 27 villages of eastern, south-eastern and southern zone of
      Nawa tehsil was done. Total 46 ground water samples were collected and analyzed
      for various physicochemical parameters as well as fluoride content. The ground
      water samples collected in clean polyethylene plastic containers were analyzed
      for pH, electrical conductivity, total dissolved salts, calcium, magnesium, total
      hardness, chloride and alkalinity. The fluoride concentration in the three
      different zones ranged from 0.64 to 14.62 mg l(-1) where 13.04% samples were
      found within permissible limit while 86.96% had fluoride beyond permissible limit
      (> 1.5 mg l(-1)). It was found that among the three different zones south-eastern
      zone was under serious fluoride contamination where fluoride concentration ranged
      between 1.10 to 14.62 mg l(-1). In the eastern zone fluoride concentration was
      recorded from 1.52 to 5.13 mg l(-1) whereas in the southern zone it was found
      between 0.64 to 3.63 mg l(-1).

PMID- 21888238
TI  - Impact of distillery effluent on germination behaviour of Brassica napus L.
AB  - The study has been focused on effect of untreated distillery effluent (Devans
      Breweries Ltd., Jammu) on germination of gobi sarson (Brassica napus. L. var.
      Punjabi Special). Six treatments (E0.... E100) each having three replicates were
      made. E0 was taken as control in which tap water was used for irrigation of the
      plants. For E20, E40, E60, E80 and E100, different concentrations i.e. 20, 40,
      60, 80 and 100% of effluent were used for irrigation, respectively. The 100%
      sample of distillery effluent analyzed for various physicochemical parameters
      showed acidic nature (pH 4.0) and higher values of COD (2496 mg l(-1)), TDS
      (799.7 mg l(-1)) and chlorides (1408 mg l(-1)). The parameters e.g. percent
      germination, germination index, speed of germination, and peak value were highest
      in treatment receiving 20% effluent concentration which also showed minimum
      values for percent inhibition, germination period, and delay index.

PMID- 21888239
TI  - Cytogenetic evaluation of Fansidar on human lymphocyte chromosomes in vitro.
AB  - Fansidar is a fixed combination of two antimalarial agents a diaminopyrimidine
      (Pyrimethamine) and a sulphonamide (Sulphadoxine) in the ratio 1:20- that have
      been used extensively worldwide for the treatment of Chloroquine resistant
      Plasmodium falciparum malaria, toxoplasmosis and Pneumocystis carinii pneumonia
      in patients with the acquired immunodeficiency syndrome. This study examined the
      effect of Fansidar on chromosomes in human lymphocyte culture. Fansidar was added
      to peripheral blood lymphocyte cultures in vitro at four different
      concentrations: 5,15, 25 and 50 microl in the ratio 1:20, 3:60, 5:100 and 10:200
      microg ml(-1). Result shows that this drug induces moderate increase in the
      frequency of gaps, breaks and rearrangements. Therefore it can be concluded that
      Fansidar has moderate clastogenic effect on human chromosomes in vitro.

PMID- 21888240
TI  - Impact of temperature on heat shock protein expression of Bombyx mori cross-breed
      and effect on commercial traits.
AB  - The present study investigated the effect of increasing temperature stress on the
      thermotolerance of B. mori cross-breed PM x CSR2 and tissue specific differential
      expression of heat shock proteins at IVth and Vth instars. The larvae reared at
      25 +/-1 degrees C and 70 +/- 5% relative humidity were treated as control. Larvae
      were subjected to heat shock temperatures of 34, 38 and 42 degrees C for 3 hr
      followed by 3 hr recovery. Expression of Heat shock protein 72 were analyzed by
      SDS-PAGE and confirmed by western blotting analysis. The impact of heat shock on
      commercial traits of cocoons was analyzed by following different strategies in
      terms of acquired thermotolerance over control. Resistance to heat shock was
      increased as larval development proceeds and increased thermotolerance is
      achieved with the induction of Heat shock protein 72 in the Vth instar larval
      haemolymph. Relative influence of heat shock temperatures on commercial traits
      corresponding to the generation of heat shock protein 72 was significantly
      improved over control. In PM x CSR2, cocoon and shell weight significantly
      increased to 9.90 and 11.90% over control respectively.

PMID- 21888241
TI  - A study on traffic noise of two campuses of University, Balasore, India.
AB  - Noise pollution is a significant environmental problem in many rapidly urbanizing
      areas of Orissa, India. Transportation sector is one of the major contributors to
      noise in these areas. The present study is an attempt to estimate traffic noise
      pollution at five places on the way from Vyasa Vihar Campus to Gyan Vigyan Vihar
      Campus of Fakir Mohan University, Balasore, Orissa. The sources of noise at the
      studied sites are predominantly attributable to motor vehicular traffic. The
      noise levels of all the five locations were found to be beyond permissible limit
      during the day time. The contributions of different types of vehicles to
      environmental noise were found to ranging from 70.4-94.2, 79.0-96.1, 77.8-110.2,
      70.8-90.3, 71.0-87.5, 71.1-84.4, 72.5-86.9 and 74.0-85.4 dB (A) by cargo carrying
      Trucks, Tractors, Dumpers, Town Buses, Motor cycles, Bolero/Trucker, Pick up and
      Tempo respectively. The contributions of individual vehicles towards noise
      pollution were found to be more than the road traffic noise-limit i.e., 70 dB
      (A). On certain local inhabitants interviewed, the impact of noise was observed
      in the forms of alterations in their physical, psychological and personal
      aspects. This study warrants attention from all sections of people to deal with
      the problem of noise pollution.

PMID- 21888242
TI  - Ecological problems of tree species in protected ecosystems of Orissa, India.
AB  - The tree layer vegetation of two protected ecosystems i.e. Similipal Biosphere
      Reserve (SBR) and Bhitarkanika National Park (BNP) of eastern ghat was analysed
      for structure, composition and diversity. With respect to the tree species
      composition the two protected ecosystems were differed from each other at the
      family, genera and species level. About 117 tree species representing 85 genera
      and 42 families were recorded in SBR. The average number of species per hectare
      was 32.5. However, a total of 29 tree species representing 22 genera and 16
      families were recorded in BNP with an average number of species per hectare of
      24.17. Species dominancy of the two protected areas was also different due to
      their difference in habitat condition. In SBR Shorea robusta was the most
      dominant species while in BNP Excoecaria agallocha was the most dominant species.
      Shannon-Wiener species diversity was 3.15 for Similipal and 2.314 for
      Bhitarkanika indicating that Similipal was highly diverse than Bhitarkanika. In
      general both the protected ecosystems of Orissa are highly rich in biodiversity
      and are characteristics of good ecological wealth of eastern ghat. Thus
      conservation and management practices are essential for the sustainability of
      their biodiversity.

PMID- 21888243
TI  - Temporal variation of phytoplankton from the tropical reservoir Valle de Bravo,
      Mexico.
AB  - Valle de Bravo reservoir is used for aquatic, fishing and as a source of drinking
      water to Mexico City. Annual data on composition, abundances, species richness
      and diversity of the phytoplankton surface community and some physical-chemical
      parameters variations were discussed. Results showed a spatial homogeneity for
      environmental descriptors and phytoplankton samples but a temporal significant
      difference between months. Pulses of high algal densities corresponded to late
      stratification (October, 103 x 10(3) cell ml(-1)), early stratification (April,
      107 x 10(3) cell ml(-1)) and plenty stratification (June, 69 x 10(3) cell ml(
      1)). Taxa that reached higher densities were: Microcystis spp., Snowella
      septentrionalis, Anabaena spp., Aphanizomenon yezoense and Fragilaria
      crotonensis. Contribution of each taxon to the total phytoplankton density showed
      that majorities were rare (41%) or dominants (40%). Frequent alternation between
      pulses and low densities and diversity of phytoplankton as well as a relative
      high number of taxa found (68), could be explained by daily strong winds,
      unstable epilimnion thickness and incorporation and extraction of substantial
      volumes of water occurred in the reservoir. Dominances of cyanobacteria and some
      chlorococcal species and a high temporal fluctuated Shannon-Wiener diversity
      index (0.45- 2.35 bits) pointing to eutrophic and perturbed conditions.

PMID- 21888244
TI  - Bioclimatic characteristic of oak species Quercus macranthera subsp. syspirensis
      and Quercus petraea subsp. pinnatiloba in Turkey.
AB  - This study was carried out to determine some bioclimatic characteristics such as
      humidity category (Q2), winter variant (m), the length of the dry season (LDS)
      and the dry season water deficit (DSWD) of naturally growing two endemic oak
      taxa, Quercus macranthera subsp. syspirensis and Q. petraea subsp. pinnatiloba,
      living in Turkey. Our findings showed that bioclimatic tolerance range of Q.
      macranthera subsp. syspirensis possess 7 different types of Mediterranean
      bioclimate while Q. petraea subsp. pinnatiloba had 8 of them. Although Q.
      macranthera subsp. syspirensis was ranging among the semiarid, freezing and very
      cold, Q. petraea subsp. pinnatiloba was among sub-humid, freezing and very cold
      ambient. It was briefly established that Q. macranthera subsp. syspirensis
      prefers semi-arid and very cold/freezing conditions and Q. petraea subsp.
      pinnatiloba prefers sub-humid and cold/very cold climatic conditions.

PMID- 21888245
TI  - Quantification of polyphenols during retting and characterization of bacteria
      from the Kadinamkulam Backwaters, Kerala.
AB  - The retting environment which provides a competitive niche for specialized
      microbes is speculated to harbour a variety of microbes with high biodegradation
      potential. In this context, an effort has been made to isolate and identify
      bacterial species having high tolerance to phenol In vitro. Maximum polyphenol
      (1.897 mg l(-1)) as observed during the initial period of retting, which
      decreased as retting proceeded. Based on biochemical characterization, the
      isolated bacterial strains were identified as Micrococcus sp., Moraxella sp.
      strain MP1, Moraxella sp. strain MP2 and Moraxella sp. strain MP3, Pseudomonas
      sp. strain PP1 and Pseudomonas sp. strain PP2, Amphibacillus sp., Brucella sp.
      strain BP1 and Brucella sp. strain BP2, Aquaspirillum sp., Escherichia coli
      strain EP1 and Escherichia coli strain EP2, Campylobacter sp., Aeromonas sp.,
      Neisseria sp., Vibrio sp., Erwinia sp. and Mesophilobacter sp. These strains were
      found to tolerate maximum concentration of phenol viz. 200 to 1000 mg l(-1).
      Plasmid analysis of phenol resistant bacterial isolates showed that almost all
      the cultures had at least one plasmid of size > 1Kb. Studies on the protein
      profile of isolated bacterial cultures showed the presence of proteins with
      molecular sizes ranging from 10 to 85 KDa with exception of Mesophilobacter and
      Neisseria having still high molecular weight protein (95 KDa). Bacterial strains
      isolated from coir-ret-liquor showed tolerance to high phenol concentration.

PMID- 21888246
TI  - Concerned by "Smilematters".

PMID- 21888247
TI  - What you should know about Michigan's new 'I'm sorry' law.

PMID- 21888248
TI  - Medical marijuana: how do you handle it in the workplace?

PMID- 21888249
TI  - Questions and answers on care and well-being issues.

PMID- 21888250
TI  - Leverage the power of prepaid debit cards.

PMID- 21888251
TI  - Dental management of the head and neck cancer patient treated with radiation
      therapy.

PMID- 21888252
TI  - Oral health care for the pregnant patient.
AB  - Pregnancy is a unique time in a woman's life, accompanied by a variety of
      physiologic, anatomic and hormonal changes that can affect how oral health care
      is provided. However, these patients are not medically compromised and should not
      be denied dental treatment simply because they are pregnant. This article
      discusses the normal changes associated with pregnancy, general considerations in
      the care of pregnant patients, and possible dental complications of pregnancy and
      their management.

PMID- 21888253
TI  - Mission to Guatemala: a life-changing experience for two Traverse City dentists.

PMID- 21888254
TI  - A care model for the future: the oncology medical home.

PMID- 21888255
TI  - Management of monoclonal gammopathy of undetermined significance (MGUS) and
      smoldering multiple myeloma (SMM).
AB  - Monoclonal gammopathy of undetermined significance (MGUS) is defined as a serum M
      protein level of less than 3 g/dL, less than 10% clonal plasma cells in the bone
      marrow, and the absence of end-organ damage. The prevalence of MGUS is 3.2% in
      the white population but is approximately twice that high in the black
      population. MGUS may progress to multiple myeloma, AL amyloidosis, Waldenstrom
      macroglobulinemia, or lymphoma. The risk of progression is approximately 1% per
      year, but the risk continues even after more than 25 years of observation. Risk
      factors for progression include the size of the serum M protein, the type of
      serum M protein, the number of plasma cells in the bone marrow, and the serum
      free light chain ratio. Smoldering (asymptomatic) multiple myeloma (SMM) is
      characterized by the presence of an M protein level of 3 g/dL or higher and/or
      10% or more monoclonal plasma cells in the bone marrow but no evidence of end
      organ damage. The overall risk of progression to a malignant condition is 10% per
      year for the first 5 years, approximately 3% per year for the next 5 years, and
      1% to 2% per year for the following 10 years. Patients with both MGUS and SMM
      must be followed up for their lifetime.

PMID- 21888256
TI  - Multiple myeloma precursor disease: current clinical and epidemiological insights
      and future opportunities.

PMID- 21888257
TI  - MGUS and smoldering myeloma: the most prevalent of plasma cell dyscrasias.

PMID- 21888258
TI  - ALK-targeted therapy for lung cancer: ready for prime time.
AB  - Lung cancer remains the leading cause of cancer-related death in the United
      States. Ongoing research into the molecular basis of lung cancer has yielded
      insight into various critical pathways that are deregulated in lung
      tumorigenesis, and in particular key driver mutations integral to cancer cell
      survival and proliferation. One of the most recent examples of this has been
      definition of translocations and functional dysregulation of the anaplastic
      lymphoma kinase (ALK) gene in a subset of patients with non-small-cell lung
      cancer. The pace of research progress in this area has been remarkable:
      chromosomal rearrangements involving this gene in lung cancer were first reported
      in 2007 by a team of investigators in Japan. Less than 3 years later, an early
      phase clinical trial of a targeted ALK inhibitor has yielded impressive responses
      in patients with advanced lung cancer containing ALK rearrangements, and
      mechanisms of acquired resistance to ALK-targeted therapy are being reported. A
      definitive study randomizing patients with ALK-mutant lung cancer to crizotinib
      (also known as PF-02341066 or 1066) versus standard therapy has recently
      completed enrollment.Taken together, these data describe a trajectory of research
      progress from basic discovery science to real-world implementation that should
      serve as a model for future integration of preclinical and clinical therapeutic
      research.

PMID- 21888259
TI  - ALK-targeted therapy in NSCLC: likely to be of benefit but not quite ready for
      prime time.

PMID- 21888260
TI  - The future of NSCLC: molecular profiles guiding treatment decisions.

PMID- 21888261
TI  - Treatment of immunoglobulin light chain (primary or AL) amyloidosis.
AB  - Not all forms of amyloidosis are systemic. Some patients may present with a
      localized form and should not be treated with chemotherapy. Some patients with
      systemic amyloidosis may have secondary, familial, or dialysis-related
      types.These types are not responsive to chemotherapy. Immunoglobulin light chain
      (primary or AL) amyloidosis is a plasma cell dyscrasia. Suppression of light
      chain production translates to organ response, improved organ function, and
      improved quality of life. This review of the various available options for the
      treatment of systemic amyloidosis is designed to help the clinician determine
      which patients are candidates for stem cell transplantation and which should be
      treated with conventional chemotherapy. The role of the recently introduced novel
      agents in management of amyloidosis is also reviewed.

PMID- 21888262
TI  - Who knows how to treat systemic light chain amyloidosis?

PMID- 21888263
TI  - Uniform risk-stratification and response criteria are paving the way to evidence
      based treatment of AL amyloidosis.

PMID- 21888264
TI  - Aloe vera (Aloe barbadensis, Aloe capensis).

PMID- 21888265
TI  - Proton therapy for prostate cancer.
AB  - Proton therapy has been used in the treatment of cancer for over 50 years. Due to
      its unique dose distribution with its spread-out Bragg peak, proton therapy can
      deliver highly conformal radiation to cancers located adjacent to critical normal
      structures. One of the important applications of its use is in prostate cancer,
      since the prostate is located adjacent to the rectum and bladder. Over 30 years
      of data have been published on the use of proton therapy in prostate cancer;
      these data have demonstrated high rates of local and biochemical control as well
      as low rates of urinary and rectal toxicity. Although before 2000 proton therapy
      was available at only a couple of centers in the United States, several new
      proton centers have been built in the last decade. With the increased
      availability of proton therapy, research on its use for prostate cancer has
      accelerated rapidly. Current research includes explorations of dose escalation,
      hypofractionation, and patient-reported quality-of-life outcomes. Early results
      from these studies are promising and will likely help make proton therapy for the
      treatment of prostate cancer more cost-effective.

PMID- 21888266
TI  - Proton therapy for prostate cancer: show me the CER!

PMID- 21888267
TI  - Back to the future: a proton pro/con.

PMID- 21888268
TI  - Monocyte phenotype and cytokine production profiles are dysregulated by short
      duration spaceflight.
AB  - INTRODUCTION: Immune system dysregulation has been demonstrated to occur during
      and immediately following spaceflight. As the initial bias and magnitude for an
      immune response is heavily influenced by monocyte/macrophage secreted cytokines,
      this study investigated monocyte phenotype and cytokine production patterns
      following short-duration spaceflight. METHODS: Secreted cytokine profiles were
      examined by cytometric bead array analysis of culture supernatants following
      whole blood culture activation with LPS or PMA+ionomycin. Nine short-duration
      Space Shuttle crewmembers participated in this study. RESULTS: Peripheral
      monocyte percentages were unaltered postflight. Constitutive monocyte expression
      of both CD62L and HLA-DR was reduced following spaceflight in a mission-specific
      fashion. Loss of either molecule indicates a functional disability of monocytes,
      either by inhibition of adhesion and tissue migration (CD62L) or by impaired
      antigen presentation (HLA-DR). Following LPS stimulation of monocytes, postflight
      expression of IL-6, TNFalpha, and IL-10 were significantly reduced (by 43%, 44%,
      and 41%, respectively) and expression of IL-1b was elevated (65%). IL-8
      production was either elevated or reduced in a mission-specific fashion.
      Following PMA+ionomycin stimulation of all leukocyte populations, only expression
      of IL-6 was significantly reduced postflight. DISCUSSION: These data indicate
      that changes in monocyte constitutive phenotype and inflammatory cytokine
      production occur following short-duration spaceflight, which may impact overall
      crewmember immunocompetence. Also, monocyte/macrophage function may be highly
      sensitive to mission specific parameters.

PMID- 21888269
TI  - Autonomic modulations during 5 hours at 4574 m (15,000 ft) breathing 40% oxygen.
AB  - INTRODUCTION: This study was done to evaluate the effects of exposure to
      hyperoxic hypobaria on the autonomic reactivity and hence G tolerance of high
      performance aircraft aircrews. METHODS: Heart rate variability (HRV) indices and
      traditional measures of autonomic functions were measured during normobaric
      baseline, hourly at hyperoxic hypobaria for 5 h, and during normobaric recovery
      in 15 subjects at an equivalent altitude of 4574 m breathing 40% oxygen. RESULTS:
      Supine and resting-sitting R-R interval, E:I ratio, and time domain indices of
      HRV increased significantly, with no change in Valsalva ratio. Power in both low-
      (LF) and high-frequency (HF) bands of HRV spectra increased significantly, which
      persisted even after normalization with mean R-R2 (LF 1177 +/- 801 at baseline to
      1837 +/- 1032 at 5 h and HF 944 +/- 683 at baseline to 1545 +/- 1095 at 5 h).
      Pressor response to handgrip was attenuated, as evident from a significant
      interaction between the effects of handgrip and hypobaria. DISCUSSION: Increases
      in R-R interval, E:I ratio, and all the time domain indices of HRV and HF power
      suggest an increase in parasympathetic influences. Increase in LF power is
      explained by the ability of the parasympathetic system to modulate the HRV
      spectrum in regions lower than respiratory frequency. Attenuation of pressor
      response to isometric handgrip contraction could have resulted from an increase
      in the transmural pressure gradient across the carotid sinuses due to hypobaria,
      which can adversely affect the anti-G straining maneuver.

PMID- 21888270
TI  - Training simulation for helicopter navigation by characterizing visual scan
      patterns.
AB  - INTRODUCTION: Helicopter overland navigation is a cognitively complex task that
      requires continuous monitoring of system and environment parameters and years of
      training. This study investigated potential improvements to training simulation
      by analyzing the influences of flight expertise on visual scan patterns. METHODS:
      There were 12 military officers who varied in flight expertise as defined by
      total flight hours who participated in overland navigation tasks. Their gaze
      parameters were tracked via two eye tracking systems while subjects were looking
      at out-the-window (OTW) and topographic Map views in a fixed based helicopter
      simulator. RESULTS: Flight performance measures were not predicted by the
      expertise level of pilots. However, gaze parameters and scan management skills
      were predicted by the expertise level. For every additional 1000 flight hours, on
      average, the model predicted the median dwell will decrease 28 ms and the number
      of view changes will increase 33 times. However, more experienced pilots scanned
      more OTW than novice pilots, which was contrary to our expectation. A
      visualization tool (FEST: Flight and Eye Scan visualization Tool) to replay
      navigation tasks and corresponding gaze data was developed. Qualitative analysis
      from FEST revealed visual scan patterns of expert pilots not only looking ahead
      on the map, but also revisiting areas on the map they just flew over to retain
      confidence in their orientation. DISCUSSION: Based on the analysis provided
      above, this work demonstrates that neurophysiological markers, such as eye
      movements, can be used to indicate the aspects of a trainee's cognitive state
      that are useful for cuing an instructional system.

PMID- 21888271
TI  - Prevalence of and biopsychosocial factors associated with low back pain in
      commercial airline pilots.
AB  - PURPOSE: The aim of this study was to examine the 12-mo prevalence of low back
      pain (LBP) and to identify individual, flight-related, and psychosocial factors
      associated with the prevalence of LBP in commercial airline pilots. METHODS: A
      cross-sectional survey was conducted with a self-administered questionnaire
      delivered by hand to 708 Thai airline pilots visiting the Institute of Aviation
      Medicine, Royal Thai Air Force, for their regular medical examinations. A
      multivariable logistic regression model was used to assess the associations
      between the prevalence of LBP and statistically significant factors. RESULTS: A
      total of 684 subjects (97%) returned the questionnaires. The 12-mo prevalence of
      self-reported LBP among commercial airline pilots was 55.7%. An elevated risk of
      experiencing LBP was associated with occasionally to frequently encountering
      turbulence in the previous year, lifting luggage four or more times per duty
      period, perception of noise in the cockpit as being too loud, and perception of
      work hazards at intermediate to high levels, assessed by the JCQ Thai version. On
      the other hand, the factors that reduced the risk of experiencing LBP were
      performing vigorous exercise regularly and having 5-23 h rest breaks between
      flights. CONCLUSIONS: LBP is common among commercial airline pilots. Our findings
      suggest that LBP in commercial airline pilots is occupation-related.
      Interventions aimed at reducing the occurrence of LBP in commercial airline
      pilots should focus on work condition adjustment and mental stress reduction.

PMID- 21888273
TI  - Optimizing medical resources for spaceflight using the integrated medical model.
AB  - INTRODUCTION: Efficient allocation of medical resources for spaceflight is
      important for crew health. The Integrated Medical Model (IMM) was developed to
      estimate medical event occurrences, mitigation, and resource requirements. An
      optimization module was created for IMM that uses a systematic process of
      elimination and preservation to maximize crew health outcomes subject to resource
      constraints. METHODS: A maximum medical kit is identified and resources are
      eliminated according to their relative impact on outcomes of interest. Additional
      steps allow opportunities for resources to be added back into the medical kit if
      possible. The effectiveness of the module is demonstrated under six alternative
      mission profiles by optimizing the medical kit to maximize the expected Crew
      Health Index (CHI), and comparisons are made with minimum and maximum kits.
      RESULTS: The optimum and maximum kits had similar expected CHI, but CHI was more
      variable for the optimum kit. The maximum kit resulted in the best outcomes, but
      required at least 13.7 times the mass of the optimum kit and 26.6 times the
      volume. The largest difference in mean CHI between the optimum and maximum kits
      occurred for four crewmembers on a 180-d mission (91.1% vs. 95.4%). CONCLUSIONS:
      The optimization module may be used as an objective tool to assist with the
      efficient allocation of medical resources for spaceflight. The module provides a
      flexible algorithm that may be used in conjunction with the IMM model to assist
      in medical kit requirements and design.

PMID- 21888272
TI  - Helicopter crashes related to oil and gas operations in the Gulf of Mexico.
AB  - INTRODUCTION: The hazards inherent in flight operations in the Gulf of Mexico
      prompted investigation of the number and circumstances of crashes related to oil
      and gas operations in the region. METHODS: The National Transportation Safety
      Board (NTSB) database was queried for helicopter crashes during 1983 through 2009
      related to Gulf of Mexico oil or gas production. The crashes were identified
      based on word searches confirmed by a narrative statement indicating that the
      flight was related to oil or gas operations. RESULTS: During 1983-2009, the NTSB
      recorded a total of 178 helicopter crashes related to oil and gas operations in
      the Gulf of Mexico, with an average of 6.6 crashes per year (5.6 annually during
      1983-1999 vs. 8.2 during 2000-2009). The crashes resulted in a total of 139
      fatalities, including 41 pilots. Mechanical failure was the most common
      precipitating factor, accounting for 68 crashes (38%). Bad weather led to 29
      crashes (16%), in which 40% of the 139 deaths occurred. Pilot error was cited by
      the NTSB in 83 crashes (47%). After crashes or emergency landings on water, 15
      helicopters sank when flotation devices were not activated automatically or by
      pilots. DISCUSSION: Mechanical failure, non-activation of flotation, and pilot
      error are major problems to be addressed if crashes and deaths in this lethal
      environment are to be reduced.

PMID- 21888274
TI  - Civilian pilot exposure to ultraviolet and blue light and pilot use of
      sunglasses.
AB  - Population and animal studies indicate that long-term exposure to short
      wavelength visible light and ultraviolet (UV) radiation causes increased risk of
      certain ocular pathologies such as cataracts and maculopathy. The potential risk
      to flight crew is unknown. The UK Civil Aviation Authority (CAA) has issued
      guidance to pilots regarding sunglass selection; however, it is not known if this
      guidance is appropriate given pilots' unique occupational environment. A search
      and appraisal of the relevant literature was conducted which showed that within
      the airline pilot population, there is limited evidence of a higher prevalence of
      cataracts. There are no data of other known UV-related ocular pathology. There is
      some evidence of higher prevalence of skin melanomas. Studies measuring cockpit
      UV radiation levels are limited and leave unanswered questions regarding airline
      pilot exposure. Data from optical transmission of cockpit windshields
      demonstrates the UV blocking properties at sea level. No studies have addressed
      the occupational use of sunglasses in airline pilots. Although it is likely that
      an aircraft windshield effectively blocks UV-B, the intensity of UV-A and short
      wavelength blue light present within the cockpit at altitude is unknown. Pilots
      may be exposed to solar radiation for periods of many hours during flight where
      UV radiation is known to be significantly greater. Aircraft windshields should
      have a standard for optical transmission, particularly of short-wavelength
      radiation. Clear, untinted prescription glasses will offer some degree of UV
      protection; however, sunglasses will offer superior protection. Any sunglasses
      used should conform to a national standard.

PMID- 21888275
TI  - Acceleration forces and cardiac and aortic indexes in jet fighter pilots.
AB  - BACKGROUND: Military jet fighter pilots are exposed to acceleration (+G(z))
      forces which possibly influence various cardiac parameters. Several previous
      studies have evaluated the impact of exposure to acceleration forces on cardiac
      morphology and function, but these studies were not prospective and were either
      based on small samples or compared jet fighter pilots with pilots of low
      performance aircraft. The purpose of this study was to evaluate the effect of
      acceleration forces on cardiac morphologic changes in jet fighter pilots.
      METHODS: Routine echocardiography has been performed for jet fighter pilots since
      2003. Medical records of all military jet fighter pilots who underwent
      echocardiography following 2003 were retrospectively evaluated. Of those, all jet
      fighter pilots who underwent an additional echocardiography prior to 2003 were
      identified. Echocardiographic parameters were recorded using M-mode and included
      left ventricular diameter at end systole and end diastole, interventricular
      septum thickness, thickness of the posterior wall, aortic root diameter and
      aortic valve opening, diameter of the left atrium, and left ventricular mass.
      Medical records of the subjects were evaluated for development of adverse events.
      RESULTS: There were 72 subjects who underwent 2 echocardiographic examinations
      with a mean follow-up period of 8.92 yr. Subjects were 18-50 yr old at the time
      of the initial echocardiographic examination. All parameters evaluated by M-mode
      were not significantly changed from the baseline examination. No adverse events
      occurred during the follow-up period. DISCUSSION: Findings of this study suggest
      that exposure to acceleration forces is not associated with cardiac and aortic
      morphologic changes.

PMID- 21888276
TI  - Decadal electrocardiographic changes between age 40 and 50 in military pilots.
AB  - INTRODUCTION: Cardiovascular diseases can lead to sudden in-flight incapacitation
      and long-term disability in aircraft pilots. Electrocardiogram (ECG) has been
      widely used to screen for these diseases in routine aeromedical examinations.
      Several ECG changes such as complete left bundle-branch block (CLBBB) and left
      ventricular hypertrophy (LVH) have been associated with increased likelihood of
      underlying structural cardiac diseases in addition to the emergence of newly
      recognized cardiovascular diseases such as Brugada syndrome. Therefore, the
      purpose of this study was to analyze decadal ECG changes in aircraft pilots
      between 40 and 50 yr in order to make an appropriate evaluation of these ECG
      changes. METHODS: We analyzed the ECGs from the annual aeromedical examination of
      age 50 compared to those 40 yr of age in a total of 176 Japan Air Self-Defense
      Force pilots. RESULTS: With regard to decadal changes, we detected 34 new ECG
      changes (1 of sinus tachycardia, 8 sinus bradycardia, 1 atrial fibrillation, 2
      premature atrial contraction, 1 premature ventricular contraction, 2 left axis
      deviation, 6 first-degree atrioventricular block, 1 CLBBB, 3 complete right
      bundle-branch block, 2 incomplete right bundle-branch block, 1 right ventricular
      conduction delay, and 6 LVH). Although the majority of them were concluded to be
      normal variants, the results of echocardiography in two hypertensive pilots
      without good control demonstrated abnormalities: one had mild hypertrophic
      nonobstructive cardiomyopathy and another had heart enlargement. CONCLUSION:
      Thus, this study recommends additional cardiovascular examinations, including
      echocardiography for hypertensive pilots with ECG changes.

PMID- 21888277
TI  - Mobility of an elastic glove for extravehicular activity without prebreathing.
AB  - INTRODUCTION: The current U.S. extravehicular activity (EVA) suit is pressurized
      at 0.29 atm, which is much lower than the pressures of sea level and inside a
      space station. Higher pressure can reduce the risk of decompression sickness
      (DCS), but mobility would be sacrificed. We have demonstrated that a glove and
      sleeve made of elastic material increased mobility when compared with those made
      of nonelastic material, such as that found in the current suit. We hypothesized
      that an elastic glove of 0.65 atm that has no risk of DCS also has greater
      mobility compared with a non-elastic glove of 0.29 atm. METHODS: The right hands
      of 10 healthy volunteers were studied in a chamber with their bare hands at
      normal ambient pressure, after donning a non-elastic glove with a pressure
      differential of 0.29 atm, and after donning an elastic glove with a pressure
      differential of 0.29 and 0.65 atm. Range of motion (ROM) of the index finger and
      surface electromyography (EMG) amplitudes during finger flexion were measured.
      RESULTS: ROM with gloves was significantly smaller than that of bare hands, but
      was similar between conditions of gloves regardless of elasticity and pressure
      differentials. However, EMG amplitudes with the elastic glove of 0.29 and 0.65
      atm were significantly smaller than those with the non-elastic glove of 0.29 atm.
      DISCUSSION: The results suggest that mobility of the elastic glove of 0.65 atm
      may be better than that of the non-elastic glove of 0.29 atm, similar to that
      used in the current EVA suit.

PMID- 21888278
TI  - Rhino-orbital-cerebral mucormycosis (ROCM): a comprehensive case review.
AB  - The objective of this paper is to review a recent case of rhino-orbital-cerebral
      mucormycosis that involved the successful treatment of an immunocompromised male
      patient that took place in a deployed military setting. In this interventional
      case review, a comprehensive evaluation of predisposing factors, presenting signs
      and symptoms, diagnostic evaluation, and treatment will be discussed in detail.
      The patient was a 38-yr-old noncompliant insulin-dependent diabetes mellitus
      Iraqi man whose initial presentation encompassed nonspecific signs and symptoms
      consistent with sinusitis. Symptoms progressed rapidly including the development
      of acute visual loss, unilateral facial edema, fixed dilated right pupil, loss of
      extraocular movements, and oropharyngeal eschar formation. With this progressive
      clinical picture, a diagnosis of mucormycosis was made in the absence of
      histological confirmation due to the nature of the deployed environment.
      Treatment included hospitalization for combined intervention with intravenous
      antifungal therapy and a series of surgeries which ultimately resulted in orbital
      exenteration and preservation of life. Successful treatment was attributed to
      having a high index of suspicion in the clinical presentation of nonspecific
      otorhinolaryngological and ophthalmological symptoms superimposed with underlying
      predisposing immunocompromised host conditions.

PMID- 21888279
TI  - Ground vasovagal presyncopes and fighter pilot fitness: aeromedical concerns.
AB  - BACKGROUND: Vasovagal episodes are common events but may have consequences for
      flight safety, particularly in high-performance aircrafts, where the autonomic
      nervous system is impacted during +G(z) accelerations. However, the risk is
      difficult to assess in the case of ground presyncopes. CASE REPORT: A 27-yr-old
      fighter pilot experienced a feeling of faintness at a daily briefing. He had
      previously shown no medical history except for a single episode. The initial
      physical examination was normal. During vagal maneuvers, the pilot developed a
      cardiac pause and a tilt-table test was positive. Other investigations were
      normal.The pilot lost consciousness twice in centrifuge testing while previous
      tests had shown a good cardiovascular tolerance. He was declared unfit to fly
      fast jets but fit as a multicrew transport pilot with a waiver. DISCUSSION: The
      epidemiology of vasovagal reactions is difficult to estimate in aircrew. A late
      occurrence in the career can be explained by either a newly acquired
      hypervagotonia, or an old predisposition with specific triggering factors in
      which psychosocial aspects are important. In such circumstances three steps are
      necessary to assess fitness: 1) to check for other etiologies; 2) to look for
      vasovagal predisposition; and 3) to check psychiatric condition. The studies
      about the predictive value of the tilt-test must be taken into account.
      CONCLUSION: In the case of vasovagal presyncope in a fighter pilot, the
      aeromedical decision should consider the medical history of the pilot, the
      results of investigations, and the experience and motivation of the individual
      under review. Centrifuge testing may be useful in difficult situations.

PMID- 21888280
TI  - Aircrew exposure to handheld laser pointers: the potential for retinal damage.
AB  - Aviation authorities around the world continue to report substantial growth in
      the incidence of laser devices being aimed at aircraft in flight. Despite
      government restrictions, affordable handheld laser devices, with a power of up to
      several thousand mW, are now easily obtainable via the Internet. Lasers of this
      power output and wavelength have a nominal ocular hazard distance of around 1000
      ft (304.8 m). Aviation medical specialists should be aware these lasers have the
      potential to cause retinal damage when aircrew operating at low altitudes are
      exposed.

PMID- 21888281
TI  - NextGen update.

PMID- 21888282
TI  - You're the flight surgeon. Labyrinthine dysfunction.

PMID- 21888283
TI  - This month in aerospace medicine history.

PMID- 21888285
TI  - [The clinic. Mother of all instruments].

PMID- 21888284
TI  - [Instituto Nacional de Psiquiatria "Ramon del la Fuente Muniz"].

PMID- 21888286
TI  - F18-FDG-PET/CT in the evaluation of patients with suspected recurrent or
      persistent locally advanced cervical carcinoma.
AB  - BACKGROUND: Cervical cancer (CC) represents the second most common neoplasm and
      the third cause of death by cancer among women. Recurrent or persistent disease
      depends on the clinical stage, but can be as high as 70%. Positron emission
      tomography/computed tomography (PET/CT) is an image study that can detect
      increased glucose uptake in tumor tissues. MATERIAL AND METHODS: PET/CT was
      performed in patients with confirmed CC, who had been previously treated, who
      developed suspected symptoms of recurrence or persistent disease with or without
      evidence of disease on a CT scan. Sensitivity, specificity, predictive values
      from PET/CT, and CT scan were evaluated. RESULTS: Sixteen patients with a mean
      age of 47.2 years were included in the study from April 2007 to June 2008.
      Thirteen patients (81.2%) were symptomatic. PET/CT was positive in 14/16 (85.7%),
      of these, 12 True positive (TP) and two, False positive (FP); meanwhile another
      two cases were True negative (TN) (12.5%). Cervix, retroperitoneal, iliac,
      obturator, and mediastinal lymph nodes were the most common anatomic sites
      detected by PET/CT. Mean number of anatomic sites with high Fluoro-deoxy-D
      glucose (FDG) uptake was two sites (range 1-7 sites). PET/CT and CT scan had 100
      and 91.7% sensitivity, respectively. Specificity for both was 50%. Positive
      predictive value (PPV) was 85.4 and 84.6%, respectively. Negative predictive
      value (NPV) was 100 and 66%, respectively, and accuracy was 88 vs. 81%,
      respectively. CONCLUSIONS: PET/CT has the capability for detecting recurrent or
      persistent cervical cancer; it detects increased metabolic activity mainly in
      primary site or lymph nodes. Further PET/CT evaluation is required to confirm the
      real impact of this study on the early detection of CC recurrence.

PMID- 21888287
TI  - Human leukocyte antigens class II genes are associated with cancer development in
      the autoimmune rheumatic diseases.
AB  - OBJECTIVE: To determine the association between HLA class II alleles and the
      probability of developing cancer in patients with autoimmune rheumatic diseases.
      MATERIAL AND METHODS; A matched case control study was conducted in which
      patients with autoimmune rheumatic disease who later developed malignancy (solid
      or lymphoproliferative) were compared with matched controls suffering from the
      same auto-immune rheumatic disease and with similar disease duration. The
      rheumatic diseases included rheumatoid arthritis, systemic lupus erythematosus,
      primary Sjogren syndrome, dermatomyositis-polymyositis, and systemic sclerosis.
      HLA-DR typing was performed by sequence-specific primers after DNA amplification
      by PCR (PCR-SSP). Statistical analysis was conducted by conditional logistic
      regression. RESULTS: HLA-DRBI*02 and DRBI*03 were found to be significantly
      associated with the probability for developing cancer (OR = 5.2 and 4.9,
      respectively), independent of family history of rheumatoid arthritis and cancer,
      recurrent sore throat, alopecia, and clinical activity of rheumatoid arthritis.
      CONCLUSIONS: The results suggest an association between HLA class II alleles with
      the probability of developing a malignant neoplasm in patients suffering from an
      autoimmune rheumatic disease.

PMID- 21888288
TI  - Weight gain and metabolic complications in preterm infants with nutritional
      support.
AB  - OBJECTIVE: To analyze the weight gain and to describe the metabolic complications
      in preterm newborns with nutritional support (NS) and to describe nutritional
      practices in the first month of hospitalization for 52 preterm newborns. MATERIAL
      AND METHODS: Descriptive and prospective study of preterm infants (30-36
      gestational weeks), with birth weight > 1 kg, hospital stay > 12 days, without
      respiratory support or complications, conducted at a public hospital in Leon,
      Guanajuato, Mexico from January to November 2006. Weight, serum glucose, insulin,
      cholesterol, triglycerides, gamma-glutamyltransferase, creatinine, urea nitrogen,
      type of NS (parenteral PN, enteral EN, mixed MN), energy content, and
      macronutrient intake were measured weekly. To obtain representative data,
      nutritional practices were not altered by the study protocol. One way ANOVA and
      Wilcoxon tests were used in data analyses. RESULTS: Overall, 52 newborns were
      included, averaging 33 gestational weeks and 1,590 g of weight. The NS was
      started by the fourth day on average. Parenteral nutrition was the most frequent
      NS during the first 2 weeks (75%). Energy and macronutrient supply was 50% less
      than the recommended. Weight gain ranged from -100 to 130 g/week. Parenteral
      nutrition showed better weekly weight gain, followed by EN. The metabolic
      complication rate per person-day was greater for MN (0.56), than for EN (0.16) or
      PN (0.09). Routine surveillance of weight and metabolic complications was
      deficient. CONCLUSIONS: Late onset of NS, insufficient energy supply, and
      deficient surveillance were obstacles to weight gain and to prevent the metabolic
      complications in these newborns.

PMID- 21888289
TI  - Munchausen syndrome by proxy in Mexican children: medical, social, psychological
      and legal aspects.
AB  - INTRODUCTION: The Munchausen Syndrome by Proxy (MSP), is considered as an unusual
      less frequent variety of child abuse (CA). In this type of abuse the perpetrators
      purposely provide factitious information, tamper with specimens or actually
      induce an illness in a child. Nowadays, it is a clinical entity described in
      pediatrics as more frequently than before. Despite the fact of its presence
      worldwide, there are still problems in order to get an appropriate diagnostic. It
      is also difficult to handle both the clinical and legal aspects in various
      countries. OBJECTIVE: Make our academic fellows aware of various pediatric,
      psychological, social and legal aspects of a series of cases attended at the
      Clinica de Atencion Integral al Nino Maltratado from Instituto Nacional de
      Pediatria (CAINM-INP), Mexico [Integral Clinic of Attention for Abused Children,
      at National Institute of Pediatrics, Mexico]. MATERIAL AND METHODS: From a series
      of 25 cases, 18 minors of age were considered with this syndrome since we found
      that they shared medical, psychological, social and legal characteristics.
      RESULTS: 18 minors of age belonged to 14 families. 4 of those families had two
      affected children each one. These affected children were girls 13/18, predominant
      in children under six years in 10/18. Syndrome expression was distributed as
      follows: fever from a non determined origin, seizures, chronic diarrhea,
      hematuria, and probable sexual abuse. 14 children were hospitalized. In all
      cases, the aggressor was the mother. The psychological evaluation of six
      perpetrators revealed psychotic, histrionic, and compulsive-obsessive traits. The
      socio-economic condition was low in 50% of the cases. A legal demand was posed
      for seven patients in which all the children remained under the custody of the
      mother. CONCLUSIONS: In Mexico, reports of CA have increased within the last
      years according to experience. Some complex forms as MSP require the
      participation of an interdisciplinary team for both diagnosis and integral
      attention.

PMID- 21888290
TI  - [Abnormalities in cervical smears stored in plastic bags: potential cause of
      false negatives].
AB  - INTRODUCTION: Cervical smear is the most economic and efficient diagnostic tool
      for the screening of cervical cancer. However, since plastic bags have been used
      in Guanajuato to transport and store smears, we have observed cytological
      abnormalities which difficult the diagnosis and lead to false negatives.
      OBJECTIVE: To describe those abnormalities. METHODS: Out of 340 women registered
      in a primary care center in Mexico, 68 were selected through systematic random
      sampling during 2007. A cervical smear was obtained and placed on two slides. The
      first sample was allowed to dry but the second one was placed into the plastic
      bag immediately after fixation. After 15 days all the smears were stained with
      the Papanicolaou technique. A certified pathologist, blinded about the variable
      of study, interpreted the samples according to the Bethesda system, and evaluated
      the presence of necrosis, edema, holes, and opportunistic microorganisms.
      RESULTS: Of the 68 smears exposed to a humid storage, 36 (53%) were inadequate
      for diagnosis (Fisher's exact probability < 0.001). From them, 36 (53%) had holes
      or lagoons, 34 (50%) had edema, 31 (46%) had necrosis, and 15 (22%) had fungus.
      On the other hand, the 68 dried cervical smears were all adequate for diagnosis
      and none had the changes or cytological abnormalities. CONCLUSION: The humid
      transport and storage of cervical smears produced abnormalities in the normal
      morphology that could lead to false negative results. The guideline for the
      handling of cervical smears must stress the importance of allowing the smears to
      dry completely after fixation and before storing them in plastic bags.

PMID- 21888291
TI  - [Role of creative discussion in the learning of critical reading of scientific
      articles].
AB  - OBJECTIVE: To compare two active educational strategies on critical reading (two
      and three stages) for research learning in medical students. MATERIAL AND
      METHODS: Four groups were conformed in a quasi-experimental design. The medical
      student group, related to three stages (critical reading guide resolution,
      creative discussion, group discussion) g1, n = 9 with school marks > 90 and g2, n
      = 19 with a < 90, respectively. The two-stage groups (guide resolution and group
      discussion) were conformed by pre-graduate interns, g3, n = 17 and g4, n = 12,
      who attended social security general hospitals. A validated and consistent survey
      with 144 items was applied to the four groups before and after educational
      strategies. Critical reading with its subcomponents: interpretation, judgment and
      proposal were evaluated with 47, 49 and 48 items, respectively. The case control
      studies, cohort studies, diagnostic test and clinical trial designs were
      evaluated. Nonparametric significance tests were performed to compare the groups
      and their results. A bias calculation was performed for each group. RESULTS: The
      highest median was obtained by the three-stage groups (g1 and g2) and so were the
      medians in interpretation, judgment and proposal. The several research design
      results were higher in the same groups. CONCLUSIONS: An active educational
      strategy with three stages is superior to another with two stages in medical
      students. It is advisable to perform these activities in goal of better learning
      in our students.

PMID- 21888292
TI  - [Intrauterine stress impairs spatial learning in the progeny of Wistar rats].
AB  - INTRODUCTION: Prenatal stress is a group of psychophysiological responses that a
      pregnant female shows when confronting by a threatening situation. This produces
      neurochemical changes that may affect hippocampal development of the offspring.
      AIM: To analyze the effects of intrauterine stress on spatial learning and memory
      of Wistar rat offspring. MATERIAL AND METHODS: Wistar rats were divided in two
      groups: Control and prenatal stress. During the critical period for the
      development of the central nervous system development (from day 12 to 18 of
      gestation), the experimental rats were exposed to prenatal stress using a
      restraint stress model. Control rats were kept under standard housing conditions.
      At 21-days postpartum, spatial learning and memory were evaluated with the Morris
      water maze. RESULTS: Intrauterine-stressed offspring showed less weight gain
      (62.7 +/- 11.7 g) compared to controls (71.3 +/- 7.4 g; t (42) = 2.87; P =
      0.006). Spatial learning assessment indicated that intrauterine-stressed animals
      showed higher escape latencies (63 +/- 14 s) than the control group (49 +/- 13
      seg; t (42) = 3.2, P = 0.003). The navigation pattern of the stress group was
      allocentric as compared to the egocentric strategy shown by controls. No
      significant statistical differences were found in memory consolidation.
      CONCLUSIONS: Intrauterine stress impairs hippocampal function during postnatal
      development. The knowledge of deleterious effects of intrauterine stress may be
      helpful in establishing primary prevention strategies of pregnant women exposed
      to this risk factor.

PMID- 21888293
TI  - [Bioactivity of thyroid hormones. Clinical significance of membrane transporters,
      deiodinases and nuclear receptors].
AB  - The study of the different factors regulating the bioactivity of thyroid hormones
      is of utmost relevance for an adequate understanding of the glandular
      pathophysiology. These factors must be considered by the clinician in order to
      achieve a successful diagnosis and treatment of glandular diseases. Among the
      factors regulating bioactivity of thyroid hormones are the following: A)
      Plasmatic membrane hormone transporters, which tissue-specific expression is
      responsible for the cellular uptake of hormones, B) A set of deiodinating enzymes
      which activate or inactivate intracellular thyroid hormone, and C) Nuclear
      receptors which are responsible for the different cellular responses at the
      transcriptional level. This review compiles analysis and discusses the most
      recent findings regarding the regulation of thyroid hormone bioactivity, as well
      as the clinical relevance of different polymorphisms and mutations currently
      described for membrane transporters and deiodinases. In addition, the main issues
      and present and future study areas are identified.

PMID- 21888294
TI  - [Blood safety in Mexico. Achievements and challenges].

PMID- 21888295
TI  - [Fabry-Anderson disease: current state of knowledge].
AB  - Fabry-Anderson disease is a lysosomal storage disease caused by deficiency of the
      enzyme alpha-galactosidase. This enzymatic defect results in the accumulation of
      glycosphingolipid into different lines cells. Usually the deficiency is complete,
      resulting in a multisystem disorder, with injury in different organs,
      predominantly heart, kidney and nervous system. However, in some patients the
      enzymatic deficit is partial and causes diverse clinical variants of the disease
      (renal or cardiac variety), this cause a difficult diagnostic and the absence of
      real epidemiology data. This review is about the epidemiology, the metabolic
      defect of this disease, it's molecular and genetics bases, the different forms of
      clinical presentation and the enzyme replacement therapy.

PMID- 21888296
TI  - Alopecia as a prominent feature of myotonic dystrophy type 1.

PMID- 21888297
TI  - Diabetic peripheral neuropathic pain: is gabapentin effective?

PMID- 21888299
TI  - Compromising the medical literature: the hidden influence of industry-biased
      articles.

PMID- 21888300
TI  - GERD treatment for chronic nonspecific cough in children and adults.

PMID- 21888301
TI  - Acellular vaccines for preventing pertussis in children.

PMID- 21888302
TI  - Diagnosis and treatment of acute pyelonephritis in women.
AB  - Acute pyelonephritis is a common bacterial infection of the renal pelvis and
      kidney most often seen in young adult women. History and physical examination are
      the most useful tools for diagnosis. Most patients have fever, although it may be
      absent early in the illness. Flank pain is nearly universal, and its absence
      should raise suspicion of an alternative diagnosis. A positive urinalysis
      confirms the diagnosis in patients with a compatible history and physical
      examination. Urine culture should be obtained in all patients to guide antibiotic
      therapy if the patient does not respond to initial empiric antibiotic regimens.
      Escherichia coli is the most common pathogen in acute pyelonephritis, and in the
      past decade, there has been an increasing rate of E. coli resistance to extended
      spectrum beta-lactam antibiotics. Imaging, usually with contrast-enhanced
      computed tomography, is not necessary unless there is no improvement in the
      patient's symptoms or if there is symptom recurrence after initial improvement.
      Outpatient treatment is appropriate for most patients. Inpatient therapy is
      recommended for patients who have severe illness or in whom a complication is
      suspected. Practice guidelines recommend oral fluoroquinolones as initial
      outpatient therapy if the rate of fluoroquinolone resistance in the community is
      10 percent or less. If the resistance rate exceeds 10 percent, an initial
      intravenous dose of ceftriaxone or gentamicin should be given, followed by an
      oral fluoroquinolone regimen. Oral beta-lactam antibiotics and
      trimethoprim/sulfamethoxazole are generally inappropriate for outpatient therapy
      because of high resistance rates. Several antibiotic regimens can be used for
      inpatient treatment, including fluoroquinolones, aminoglycosides, and
      cephalosporins.

PMID- 21888303
TI  - Evaluation and management of orthostatic hypotension.
AB  - Orthostatic hypotension is defined as a decrease in systolic blood pressure of 20
      mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within three minutes
      of standing when compared with blood pressure from the sitting or supine
      position. It results from an inadequate physiologic response to postural changes
      in blood pressure. Orthostatic hypotension may be acute or chronic, as well as
      symptomatic or asymptomatic. Common symptoms include dizziness, lightheadedness,
      blurred vision, weakness, fatigue, nausea, palpitations, and headache. Less
      common symptoms include syncope, dyspnea, chest pain, and neck and shoulder pain.
      Causes include dehydration or blood loss; disorders of the neurologic,
      cardiovascular, or endocrine systems; and several classes of medications.
      Evaluation of suspected orthostatic hypotension begins by identifying reversible
      causes and underlying associated medical conditions. Head-up tilt-table testing
      can aid in confirming a diagnosis of suspected orthostatic hypotension when
      standard orthostatic vital signs are nondiagnostic; it also can aid in assessing
      treatment response in patients with an autonomic disorder. Goals of treatment
      involve improving hypotension without excessive supine hypertension, relieving
      orthostatic symptoms, and improving standing time. Treatment includes correcting
      reversible causes and discontinuing responsible medications, when possible.
      Nonpharmacologic treatment should be offered to all patients. For patients who do
      not respond adequately to nonpharmacologic treatment, fludrocortisone, midodrine,
      and pyridostigmine are pharmacologic therapies proven to be beneficial.

PMID- 21888304
TI  - Orthostatic hypotension.

PMID- 21888305
TI  - Screening for developmental delay.
AB  - According to the literature, 12 to 16 percent of children in the United States
      have at least one developmental delay, yet as many as one-half of affected
      children will not be identified by the time they enter kindergarten. If
      developmental delays are detected too late, opportunities for early intervention
      may be lost. Empirical literature on clinical recommendations for developmental
      delay screening in primary care is inconsistent and often insufficient to direct
      the family physician. In addition, multiple barriers exist, which often prevent
      physicians from performing initial screening and completing additional evaluation
      and referrals. Implementing office-based systems for screening and referrals may
      overcome these barriers and improve outcomes. Recent studies support the use of a
      validated screening tool at regular, repeated intervals, in addition to physician
      surveillance, at all well-child visits. The literature also supports screening
      for developmental delay with parent-completed tools rather than directly
      administered tools. The most extensively evaluated parent-completed tools are the
      Parents' Evaluation of Developmental Status and the Ages and Stages
      Questionnaire. Family physicians should be familiar with currently available
      screening tools, as well as their limitations and strengths. Additional
      evaluations and referrals are recommended if developmental delay is identified or
      suspected.

PMID- 21888306
TI  - Pharmacologic treatment of hyperlipidemia.
AB  - Pharmacologic treatment of hyperlipidemia in conjunction with therapeutic
      lifestyle changes can be used for both primary and secondary prevention of
      cardiovascular disease. Statins have the most convincing data for primary
      prevention, especially for higher risk patients. Therefore, risk stratification
      is essential. Statin therapy is also recommended for secondary prevention in all
      patients with known cardiovascular disease or the risk equivalent. High-dose
      statins should be initiated in patients with acute coronary syndrome. Omega-3
      fatty acids may be a good alternative after myocardial infarction for patients
      who cannot tolerate statins. Fibrates and niacin have not been shown to reduce
      all-cause mortality in secondary prevention, but may be useful adjuncts when
      statins alone cannot adequately control lipid levels. Other cholesterol-lowering
      medications used for primary or secondary prevention of cardiovascular disease
      have not been shown to consistently improve patient-oriented outcomes. There is
      good evidence for using statins in the secondary prevention of stroke and
      peripheral arterial disease.

PMID- 21888307
TI  - Medicines for lowering cholesterol.

PMID- 21888308
TI  - Persistent rash in a child: lichen striatus.

PMID- 21888309
TI  - AAO-HNS Guidelines for Tonsillectomy in Children and Adolescents.

PMID- 21888310
TI  - Production of Galacto-oligosaccharides by the beta-Galactosidase from
      Kluyveromyces lactis : comparative analysis of permeabilized cells versus soluble
      enzyme.
AB  - The transgalactosylation activity of  Kluyveromyces lactis  cells was studied in
      detail. Cells were permeabilized with ethanol and further lyophilized to
      facilitate the transit of substrates and products. The resulting biocatalyst was
      assayed for the synthesis of galacto-oligosaccharides (GOS) and compared with two
      soluble beta-galactosidases from K. lactis (Lactozym 3000 L HP G and Maxilact LGX
      5000). Using 400 g/L lactose, the maximum GOS yield, measured by HPAEC-PAD
      analysis, was 177 g/L (44% w/w of total carbohydrates). The major products
      synthesized were the disaccharides 6-galactobiose [Gal-beta(1->6)-Gal] and
      allolactose [Gal-beta(1->6)-Glc], as well as the trisaccharide 6-galactosyl
      lactose [Gal-beta(1->6)-Gal-beta(1->4)-Glc], which was characterized by MS and 2D
      NMR. Structural characterization of another synthesized disaccharide, Gal-beta(1
      >3)-Glc, was carried out. GOS yield obtained with soluble beta-galactosidases was
      slightly lower (160 g/L for Lactozym 3000 L HP G and 154 g/L for Maxilact LGX
      5000); however, the typical profile with a maximum GOS concentration followed by
      partial hydrolysis of the newly formed oligosaccharides was not observed with the
      soluble enzymes. Results were correlated with the higher stability of beta
      galactosidase when permeabilized whole cells were used.

PMID- 21888311
TI  - The self-consistent field study of the adsorption of flexible polyelectrolytes
      onto two charged nano-objects.
AB  - The continuum self-consistent field theory (SCFT) is applied to the study of the
      adsorption of flexible polyelectrolyte (PE) onto the surfaces of two two
      dimensional charged square objects with a constant electric field strength
      immersed in a weakly charged polyelectrolyte solution. The dependences of the
      different chain conformations, that is, bridging, loop, tail, and train, and in
      particular, the bridging chain conformation, on various system parameters (the
      charge fraction of the PE chains, the surface charge density, the object size,
      the salt concentration, etc.) are investigated. The efficient multigrid method is
      adopted to numerically solve the modified diffusion equation and the Poisson
      equation. It is found that the thickness L(B) of the boundary layer of the
      adsorbed PE chains is independent of the chain length and scales with the surface
      charge density sigma and the fraction of charges on PE chains alpha(P) as L(B) ~
      sigma(-0.36) and L(B) ~ alpha(P)(-0.36), respectively. Simulation results reveal
      that the total amount of bridging chain conformation in the system scales
      linearly with respect to the size of the charge objects and scales linearly with
      the chain length in the long polymer chain regime. Simulation results reveal that
      the total amount of the bridging chain conformation in the system scales with the
      charge fraction of PE chains as a power law and the scaling exponent is dependent
      on all of the other system parameters. Simulation results show that the total
      amount of charges on the adsorbed chains in the system can overcompensate the
      surface charges for relatively long chains with high charge fractions.

PMID- 21888312
TI  - Ultrasensitive aptamer-based multiplexed electrochemical detection by coupling
      distinguishable signal tags with catalytic recycling of DNase I.
AB  - This work reports an aptamer-based, disposable, and multiplexed sensing platform
      for simultaneous electrochemical determination of small molecules, employing
      adenosine triphosphate (ATP) and cocaine as the model target analytes. The
      multiplexed sensing strategy is based on target-induced release of
      distinguishable redox tag-conjugated aptamers from a magnetic graphene platform.
      The electronic signal of the aptasensors could be further amplified by coupling
      DNase I with catalytic recycling of self-produced reactants. The assay was based
      on the change in the current at the various peak potentials in the presence of
      the corresponding signal tags. Experimental results revealed that the multiplexed
      electrochemical aptasensor enabled the simultaneous monitoring of ATP and cocaine
      in a single run with wide working ranges and low detection limits (LODs: 0.1 pM
      for ATP and 1.5 pM for cocaine). This concept offers promise for rapid, simple,
      and cost-effective analysis of biological samples.

PMID- 21888313
TI  - Rheological behavior of clay-nanoparticle hybrid-added bentonite suspensions:
      specific role of hybrid additives on the gelation of clay-based fluids.
AB  - Two different types of clay nanoparticle hybrid, iron oxide nanoparticle clay
      hybrid (ICH) and Al(2)O(3)-SiO(2) nanoparticle clay hybrid (ASCH), were
      synthesized and their effects on the rheological properties of aqueous bentonite
      fluids in steady state and dynamic state were explored. When ICH particles were
      added, bentonite particles in the fluid cross-link to form relatively well
      oriented porous structure. This is attributed to the development of positively
      charged edge surfaces in ICH that leads to strengthening of the gel structure of
      the bentonite susensions. The role of ASCH particles on the interparticle
      association of the bentonite fluids is different from that of ICH and sensitive
      to pH. As pH of ASCH-added bentonite suspensions increased, the viscosity, yield
      stress, storage modulus, and flow stress decreased. In contrast, at low pH, the
      clay suspensions containing ASCH additives were coagulated and their rheological
      properties become close to those of ICH added bentonite fluids. A correlation
      between the net surface charge of the hybrid additives and the rheological
      properties of the fluids indicates that the embedded nanoparticles within the
      interlayer space control the variable charge of the edge surfaces of the
      platelets and determine the particles association behavior of the clay fluids.

PMID- 21888314
TI  - Dynamic isolation and unloading of target proteins by aptamer-modified
      microtransporters.
AB  - We describe here a new strategy for isolating target proteins from complex
      biological samples based on an aptamer-modified self-propelled microtube engine.
      For this purpose, a thiolated thrombin or a mixed thrombin-ATP aptamer
      (prehybridized with a thiolated short DNA) was coassembled with mercaptohexanol
      onto the gold surface of these microtube engines. The rapid movement of the
      aptamer-modified microtransporter resulted in highly selective and rapid capture
      of the target thrombin, with an effective discrimination against a large excess
      of nontarget proteins. Release of the captured thrombin can be triggered by the
      addition of ATP that can bind and displace the immobilized mixed thrombin-ATP
      aptamer in 20 min. The rapid loading and unloading abilities demonstrated by
      these selective microtransporters are illustrated in complex matrixes such as
      human serum and plasma. The new motion-driven protein isolation platform
      represents a new approach in bioanalytical chemistry based on active transport of
      proteins and offers considerable promise for diverse diagnostic applications.

PMID- 21888315
TI  - Synthetic and structural studies of donor-functionalized alkoxy derivatives of
      gallium.
AB  - The synthesis of a range of alkyl/chloro-gallium alkoxide and amido/alkoxide
      compounds was achieved via a series of protonolysis and alcoholysis steps. The
      initial reaction involved the synthesis of [Me(Cl)Ga{N(SiMe(3))(2)}](2) (1) via
      methyl group transfer from the reaction of GaCl(3) with two equivalents of
      LiN(SiMe(3))(2). Reaction of 1 with varying amounts of ROH resulted in the
      formation of [Me(Cl)Ga(OR)](2) (2, R = CH(2)CH(2)OMe; 3, CH(CH(3))CH(2)NMe(2)),
      [Me(Cl)Ga{N(SiMe(3))(2)}(MU(2)-OR)Ga(Cl)Me] (4, R = CH(2)CH(2)NMe(2)), or
      [MeGa(OR)(2)] (5, R = CH(CH(3))CH(2)NMe(2)). Compound 4 represents an
      intermediate in the formation of dimeric complexes, of the type
      [Me(Cl)Ga(OR)](2), when formed from compound [Me(Cl)Ga{N(SiMe(3))(2)}](2). A
      methylgallium amido/alkoxide complex [MeGa{N(SiMe(3))(2)}(OCH(2)CH(2)OMe)](2) (6)
      was isolated when 2 was further reacted with LiN(SiMe(3))(2). In addition,
      reaction of 2 with HO(t)Bu resulted in a simple alcohol/alkoxide exchange and
      formation of [Me(Cl)Ga(O(t)Bu)](2) (7). In contrast to the formation of 1, the in
      situ reaction of GaCl(3) with one equivalent of LiN(SiMe(3))(2) yielded
      [Cl(2)Ga{N(SiMe(3))(2)}](2) in low yield, where no methyl group transfer has
      occurred. Reaction of alcohol with [Cl(2)Ga{N(SiMe(3))(2)}](2) was then found to
      yield [Cl(2)Ga(OR)](2) (8, R = CH(2)CH(2)NMe(2)), and further reaction of 8 with
      LiN(SiMe(3))(2) yielded the gallium amido alkoxide complex,
      [ClGa{N(SiMe(3))(2)}(OR)](2) (9, R = CH(2)CH(2)NMe(2)), similar to 6. The
      structures of compounds 4, 5, 7, and 8 have been determined by single-crystal X
      ray diffraction.

PMID- 21888317
TI  - Interfacial and self-aggregation of binary mixtures of anionic and nonionic
      amphiphiles in aqueous medium.
AB  - Interfacial and bulk properties of sodium dodecyl sulfate (SDS), polyoxyethylene
      (20) sorbitan monooleate (Tween-80), and their binary mixtures in aqueous medium
      have been investigated using surface tension, conductance, and fluorescence
      measurements at different temperatures. The critical micelle concentration (CMC),
      counterion binding, polarity index, aggregation number, thermodynamics of
      interfacial adsorption, and micellization are evaluated. The entropic
      contribution is found to be the predominant factor in micelle formation. The
      aggregation number and the polarity index of the micelle interior estimated by
      the pyrene fluorescence technique show interesting temperature dependence. The
      size and composition of the mixed micelles vary with the total concentration. The
      micellar compositions, activities of the individual components in the mixed
      species, and intersurfactant interactions are also estimated following regular
      solution theory, excess thermodynamic functions, and a molecular thermodynamic
      model. The surfactant mixtures are found to be nonideal with a lower degree of
      counterion binding compared to the individual members. Mixed micelles are
      nonspherical in nature at all temperatures when the mole fraction (alpha) of the
      ionic part in mixtures is high but transform to spherical when alpha(SDS) is
      <=0.50.

PMID- 21888316
TI  - NMR in metabolomics and natural products research: two sides of the same coin.
AB  - Small molecules are central to biology, mediating critical phenomena such as
      metabolism, signal transduction, mating attraction, and chemical defense. The
      traditional categories that define small molecules, such as metabolite, secondary
      metabolite, pheromone, hormone, and so forth, often overlap, and a single
      compound can appear under more than one functional heading. Therefore, we favor a
      unifying term, biogenic small molecules (BSMs), to describe any small molecule
      from a biological source. In a similar vein, two major fields of chemical
      research,natural products chemistry and metabolomics, have as their goal the
      identification of BSMs, either as a purified active compound (natural products
      chemistry) or as a biomarker of a particular biological state (metabolomics).
      Natural products chemistry has a long tradition of sophisticated techniques that
      allow identification of complex BSMs, but it often fails when dealing with
      complex mixtures. Metabolomics thrives with mixtures and uses the power of
      statistical analysis to isolate the proverbial "needle from a haystack", but it
      is often limited in the identification of active BSMs. We argue that the two
      fields of natural products chemistry and metabolomics have largely overlapping
      objectives: the identification of structures and functions of BSMs, which in
      nature almost inevitably occur as complex mixtures. Nuclear magnetic resonance
      (NMR) spectroscopy is a central analytical technique common to most areas of BSM
      research. In this Account, we highlight several different NMR approaches to
      mixture analysis that illustrate the commonalities between traditional natural
      products chemistry and metabolomics. The primary focus here is two-dimensional
      (2D) NMR; because of space limitations, we do not discuss several other important
      techniques, including hyphenated methods that combine NMR with mass spectrometry
      and chromatography. We first describe the simplest approach of analyzing 2D NMR
      spectra of unfractionated mixtures to identify BSMs that are unstable to chemical
      isolation. We then show how the statistical method of covariance can be used to
      enhance the resolution of 2D NMR spectra and facilitate the semi-automated
      identification of individual components in a complex mixture. Comparative studies
      can be used with two or more samples, such as active vs inactive, diseased vs
      healthy, treated vs untreated, wild type vs mutant, and so on. We present two
      overall approaches to comparative studies: a simple but powerful method for
      comparing two 2D NMR spectra and a full statistical approach using multiple
      samples. The major bottleneck in all of these techniques is the rapid and
      reliable identification of unknown BSMs; the solution will require all the
      traditional approaches of both natural products chemistry and metabolomics as
      well as improved analytical methods, databases, and statistical tools.

PMID- 21888318
TI  - Liquid water transport in polylactide homo and graft copolymers.
AB  - The successful design of new biodegradable, renewable resource plastics as
      replacements to commodity barrier plastics would benefit from an accurate
      measurement of sorption and diffusion of liquids. In this study, the diffusion of
      liquid water in amorphous polylactide [PLA] and a PLA graft copolymer, poly(1,5
      cyclooctadiene-co-5-norbornene-2-methanol-graft-dl-lactide) [PCNL], was examined
      with time-resolved Fourier transform infrared attenuated total reflectance (FTIR
      ATR) spectroscopy. Non-Fickian behavior was observed for all experiments,
      indicated by a slow approach to steady state due to diffusion and polymer
      relaxation occurring on similar time scales. This non-Fickian behavior highlights
      the variability of the sorption isotherms reported in the literature, where
      others have collected nonequilibrium sorption behavior (instead of true steady
      state equilibrium sorption) at different time points and film thicknesses. The
      dynamic infrared data provided direct evidence for both water diffusion and water
      induced polymer relaxation, where both were quantified and regressed to a
      diffusion-relaxation model to determine the diffusion coefficient and the polymer
      relaxation time constant. In addition to the successful measurement and modeling
      of the diffusion-relaxation phenomena for diffusion of a liquid in a
      nonequilibrium state glassy polymer, this study also determined that the
      diffusivity of water in the PLA graft copolymer (with only 5 wt % rubber) was 3
      fold lower than in the PLA homopolymer.

PMID- 21888319
TI  - A combined experimental and computational thermodynamic study of the isomers of
      pyrrolecarboxaldehyde and 1-methyl- pyrrolecarboxaldehyde.
AB  - The present paper reports an experimental calorimetric study of 2
      pyrrolecarboxaldehyde and 1-methyl-2-pyrrolecarboxaldehyde, which aims to
      determine their standard (p degrees  = 0.1 MPa) molar enthalpies of formation, in
      the gaseous phase, at T = 298.15 K. These values were derived from the standard
      (p degrees  = 0.1 MPa) molar enthalpies of formation, in the condensed phase,
      Delta(f)H(m) degrees (cr,l), at T = 298.15 K, obtained from the standard molar
      enthalpies of combustion, DeltacHm degrees , measured by static bomb combustion
      calorimetry, and from the standard molar enthalpies of phase transition,
      Delta(cr,l)(g) H(m) degrees  at T = 298.15 K, obtained by high temperature Calvet
      microcalorimetry. Additionally, the standard enthalpies of formation of these two
      compounds were estimated by computations based on standard ab initio molecular
      calculations at the G3(MP2)//B3LYP level. The estimated values are in very good
      agreement with experimental data, giving us support to estimate the gas-phase
      enthalpies of formation of the 3-pyrrolecarboxaldehyde and 1-methyl-3
      pyrrolecarboxaldehyde that were not studied experimentally. N-H bond dissociation
      enthalpies, gas-phase acidities and basicities, proton and electron affinities,
      and adiabatic ionization enthalpies were also calculated. Furthermore, the
      molecular structure of the four molecules was established and the structural
      parameters were determined at the B3LYP/6-31G(d) level of theory.

PMID- 21888320
TI  - Influence of electrostatic and chemical heterogeneity on the electric-field
      induced destabilization of thin liquid films.
AB  - A numerical model for thin liquid film (<100 nm) drainage in the presence of an
      external electric field is developed. Long-wave theory is applied to approximate
      and simplify the governing equations. A spatiotemporal film morphology evolution
      equation thus obtained is then solved using a combination of finite difference to
      resolve the spatial dimensions and an adaptive time step ODE solver for the
      temporal propagation. The effect of fluid properties, namely, viscosity and
      surface tension, on the film drainage time is observed for a homogeneous electric
      field, which leads to random dewetting spots. Electrically heterogeneous fields,
      achieved by modeling electrodes with various periodic patterns, are explored to
      identify their effect on the drainage time and behavior. Finally, the chemical
      heterogeneity of the substrate is coupled with the periodic electric
      heterogeneity to understand the implications of combined heterogeneity. It is
      observed that the introduction of any heterogeneity results in faster drainage of
      the film when compared to that of the homogeneous field. In all cases, the thin
      film is drained, leaving submicrometer-scale structures at the interface. Well
      controlled surface patterns are found on the application of periodic
      heterogeneity. This study effectively demonstrates the immense potential of
      electrically induced thin film drainage as a means for faster de-emulsification
      and for the creation of ordered submicrometer-scale surface patterns on soft
      materials.

PMID- 21888321
TI  - CH...pi interactions do not contribute to hydrogen transfer catalysis by glycerol
      dehydratase.
AB  - The role of the nonbonded CH...pi interaction in the hydrogen abstraction from
      glycerol by the coenzyme B(12)-independent glycerol dehydratase (GDH) was
      examined using the QM/MM (ONIOM), MP2, and CCSD(T) methods. The studied CH...pi
      interaction included the hydrogen atom of the -C(2)H(OH)- group of the glycerol
      substrate and the tyrosine-339 residue of the dehydratase. A contribution of this
      interaction to the stabilization of the transition state for the transfer of a
      hydrogen atom from the adjacent terminal C(1)H(2)(OH) group to cysteine 433 was
      determined by ab initio HF, MP2, and CCSD(T) calculations with the aug-cc-pvDZ
      basis set for the corresponding methane/benzene, methanol/phenol, and glycerol
      radical/phenol subsystems. The calculated CH...pi distance, defined as the
      distance between the H atom and the center of the phenol ring, shortened from
      2.62 to 2.52 A upon going from the ground- to the transition-state of the GDH
      catalyzed reaction. However, this shortening was not accompanied by the expected
      lowering of the CH...pi interaction free energy. Instead, this interaction
      remained weak (about -1 kcal/mol) along the entire reaction coordinate.
      Additionally, the mutual orientation of the CH group and the phenol ring did not
      change significantly during the reaction. These results suggest that the phenol
      group of the tyrosine-339 does not contribute to lowering the activation barrier
      in the enzyme, but do not exclude the possibility that tyrosine 339 facilitates
      proper orientation of glycerol for the electrostatic catalysis, or inhibits side
      reactions of the reactive glycerol radical intermediate.

PMID- 21888322
TI  - Structural, dynamical, and electronic transport properties of modified DNA
      duplexes containing size-expanded nucleobases.
AB  - Among the distinct strategies proposed to expand the genetic alphabet, size
      expanded nucleobases are promising for the development of modified DNA duplexes
      with improved biotechnological properties. In particular, duplexes built up by
      replacing canonical bases with the corresponding benzo-fused counterparts could
      be valuable as molecular nanowires. In this context, this study reports the
      results of classical molecular dynamics simulations carried out to examine the
      structural and dynamical features of size-expanded DNAs, including both hybrid
      duplexes containing mixed pairs of natural and benzo-fused bases (xDNA) and pure
      size-expanded (xxDNA) duplexes. Furthermore, the electronic structure of both
      natural and size-expanded duplexes is examined by means of density functional
      computations. The results confirm that the structural and flexibility properties
      of the canonical DNA are globally little affected by the presence of benzo-fused
      bases. The most relevant differences are found in the enhanced size of the
      grooves, and the reduction in the twist. However, the analysis also reveals
      subtle structural effects related to the nature and sequence of benzo-fused bases
      in the duplex. On the other hand, electronic structure calculations performed for
      xxDNAs confirm the reduction in the HOMO-LUMO gap predicted from the analysis of
      the natural bases and their size-expanded counterparts, which suggests that pure
      size-expanded DNAs can be good conductors. A more complex situation is found for
      xDNAs, where fluctuations in the electrostatic interaction between base pairs
      exerts a decisive influence on the modulation of the energy gap.

PMID- 21888323
TI  - Exploring the rich energy landscape of sulfate-water clusters SO4(2-) (H2O)(n=3
      7): an electronic structure approach.
AB  - We present a reinvestigation of sulfate-water clusters SO4(2-) (H2O)(n=3-7),
      which involves several new aspects. Using a joint molecular mechanics/first
      principles approach, we perform exhaustive searches for stable cluster
      geometries, showing that the sulfate-water landscape is much richer than
      anticipated previously. We check the compatibility of the new structures with
      experiment by comparing vertical detachment energies (VDEs) calculated at the
      B3LYP/6-311++G** level of theory and determine the energetic ordering of the
      isomers at the RI-MP2/aug-cc-pVTZ level. Our results are bench-marked carefully
      against reference energies of estimated CCSD(T)/aug-cc-VTZ quality and VDEs of
      CCSD(T)/aug-cc-pVDZ quality. Furthermore, we calculate anharmonic vibrational
      corrections for up to the n = 6 clusters, which are shown to be significant for
      isomer energy ordering. We use energy decomposition analysis (EDA) based on the
      absolutely localized fragment (ALMO) expansion to gain chemical insight into the
      binding motifs.

PMID- 21888324
TI  - Structure of 2,4-diaminopyrimidine-theobromine alternate base pairs.
AB  - We report the structure of clusters of 2,4-diaminopyrimidine with 3,7
      dimethylxanthine (theobromine) in the gas phase determined by IR-UV double
      resonance spectroscopy in both the near-IR and mid-IR regions in combination with
      ab initio computations. These clusters represent potential alternate nucleobase
      pairs, geometrically equivalent to guanine-cytosine. We have found the four
      lowest energy structures, which include the Watson-Crick base pairing motif. This
      Watson-Crick structure has not been observed by resonant two-photon ionization
      (R2PI) in the gas phase for the canonical DNA base pairs.

PMID- 21888325
TI  - Enantioselective total synthesis of the potent anti-HIV nucleoside EFdA.
AB  - A concise enantioselective total synthesis of 4'-ethynyl-2-fluoro-2'
      deoxyadenosine (EFdA), an extremely potent anti-HIV agent, has been accomplished
      from (R)-glyceraldehyde acetonide in 18% overall yield by a 12-step sequence
      involving a highly diastereoselective ethynylation of an alpha-alkoxy ketone
      intermediate.

PMID- 21888326
TI  - Enantioselective synthesis of sphingadienines and aromatic ceramide analogs.
AB  - A new approach to the synthesis of sphingoid bases has been developed. The
      strategy is based on Sonogashira coupling of a chiral acetylenic carbamate that
      can be prepared in enantiomerically enriched form from 2,3-epoxy-4-pentyn-1-ol,
      which is readily accessible by Sharpless asymmetric epoxidation. Several N-Boc
      sphingadienines and aromatic ceramide analogs have been synthesized.

PMID- 21888327
TI  - Novel approach to the lundurine alkaloids: synthesis of the tetracyclic core.
AB  - The tetracyclic core of the lundurine family of alkaloids has been synthesized by
      a novel approach that features a double ring-closing olefin metathesis to form
      the five-and eight-membered rings.

PMID- 21888330
TI  - Combining monitoring data and modeling identifies PAHs as emerging contaminants
      in the arctic.
AB  - Protecting Arctic ecosystems against potential adverse effects from anthropogenic
      activities is recognized as a top priority. In particular, understanding the
      accumulation and effects of persistent organic pollutants (POPs) in these
      otherwise pristine ecosystems remains a scientific challenge. Here, we combine
      more than 20,000 tissue concentrations, a food web bioaccumulation model, and
      time trend analyses to demonstrate that the concentrations of legacy-POPs in the
      Barents/Norwegian Sea fauna decreased 10-fold between 1985 and 2010, which
      reflects regulatory efforts to restrict these substances. In contrast,
      concentrations of fossil fuel derived PAHs in lower trophic levels (invertebrates
      and fish) increased 10 to 30 fold over the past 25 years and now dominate the
      summed POP burden (25 POPs, including 11 PAHs) in these biota. Before 2000, PCBs
      dominated the summed POP burden in top predators. Our findings indicate that the
      debate on the environmental impacts of fossil fuel burning should move beyond the
      expected seawater temperature increase and examine the possible environmental
      impact of fossil fuel derived PAHs.

PMID- 21888331
TI  - Manganese(II)-containing MRI contrast agent employing a neutral and non
      macrocyclic ligand.
AB  - The ligand N,N'-bis(2-pyridylmethyl)-bis(ethylacetate)-1,2-ethanediamine (debpn)
      coordinates divalent transition metal ions in either a pentadentate or
      hexadentate fashion. The coordination number correlates with the ionic radius of
      the metal ion, with larger cations being heptacoordinate as assessed by solid
      state analysis. With Mn(II), the debpn ligand is hexadentate and remains bound to
      the oxophilic metal ion, even when dissolved in water. The ligand's incomplete
      coordination of the manganous ion allows water molecules to coordinate to the
      metal center. These two properties, coupled with the high paramagnetism
      associated with the S = 5/2 metal center, enable [Mn(debpn)(H(2)O)](ClO(4))(2) to
      serve as a stable and effective magnetic resonance imaging contrast agent despite
      the ligand's lack of both a macrocyclic component and an anionic charge.

PMID- 21888332
TI  - Electronic state of a conducting single molecule magnet based on Mn-salen type
      and Ni-dithiolene complexes.
AB  - The electrochemical oxidation of an acetone solution containing [Mn(III) (5
      MeOsaltmen)(H(2)O)](2)(PF(6))(2) (5-MeOsaltmen(2-) = N,N'-(1,1,2,2
      tetramethylethylene)bis(5-methoxysalicylideneiminate)) and (NBu(4))[Ni(dmit)(2)]
      (dmit(2-) = 2-thioxo-1,3-dithiole-4,5-dithiolate) afforded a hybrid material,
      [Mn(5-MeOsaltmen)(acetone)](2)[Ni(dmit)(2)](6) (1), in which [Mn(2)](2+) single
      molecule magnets (SMMs) with an S(T) = 4 ground state and [Ni(dmit)(2)](n-)
      molecules in a charge-ordered state (n = 0 or 1) are assembled in a layer-by
      layer structure. Compound 1 crystallizes in the triclinic space group P1 with an
      inversion center at the midpoint of the Mn...Mn dimer. The [Mn(2)](2+) unit has a
      typical nonplanar Mn(III) dimeric core and is structurally consistent with
      previously reported [Mn(2)] SMMs. The six [Ni(dmit)(2)](n-) (n = 0 or 1) units
      have a square-planar coordination geometry, and the charge ordering among them
      was assigned on the basis of nu(C?C) in IR reflectance spectra (1386, 1356, 1327,
      and 1296 cm(-1)). The [Mn(2)](2+) SMM and [Ni(dmit)(2)](n-) units aggregate
      independently to form hybrid frames. Electronic conductivity measurements
      revealed that 1 behaved as a semiconductor (rho(rt) = 2.1 * 10(-1) Omega.cm(-1),
      E(a) = 97 meV) at ambient pressure and as an insulator at 1.7 GPa (rho(1.7GPa) =
      4.5 Omega.cm(-1), E(a) = 76 meV). Magnetic measurements indicated that the
      [Mn(2)](2+) units in 1 behaved as S(T) = 4 SMMs at low temperatures.

PMID- 21888334
TI  - Structural reassignment of cytosporolides A-C via biomimetic synthetic studies
      and reinterpretation of NMR data.
AB  - A structure revision for the recently isolated fungal meroterpenoids,
      cytosporolides A-C, is suggested based on biosynthetic speculation and
      reinterpretation of existing spectroscopic data. The structure revision is
      supported by a biomimetic synthetic study, featuring a [4 + 2] cycloaddition
      reaction between a presumed o-quinone methide intermediate and beta
      caryophyllene.

PMID- 21888333
TI  - NH+-F hydrogen bonding in a fluorinated "proton sponge" derivative: integration
      of solution, solid-state, gas-phase, and computational studies.
AB  - We report detailed studies on the characterization of an intramolecular NH-F
      hydrogen bond formed within a fluorinated "proton sponge" derivative. An ammonium
      ion, generated from 8-fluoro-N,N-dimethylnaphthalen-1-amine, serves as a charged
      hydrogen bond donor to a covalently bound fluorine appropriately positioned on
      the naphthalene skeleton. Potentiometric titrations of various N,N
      dimethylnaphthalen-1-amines demonstrate a significant increase in basicity when
      hydrogen bonding is possible. X-ray crystallography reveals that NH-F hydrogen
      bonding in protonated 8-fluoro-N,N-dimethylnaphthalen-1-amine is heavily
      influenced by ion pairing in the solid state; bifurcated and trifurcated hydrogen
      bonds are formed depending on the counterion utilized. Compelling evidence of
      hydrogen bonding in the 8-fluoro-N,N-dimethylnaphthyl-1-ammonium cation is
      provided by gas-phase cryogenic vibrational photodissociation spectroscopy.
      Solution-phase infrared spectroscopy provides complementary results, and the
      frequencies of the N-H stretching mode in both phases are in excellent agreement
      with the computed vibrational spectra. NMR analysis of protonated 8-fluoro-N,N
      dimethylnaphthalen-1-amine demonstrates significant H-F coupling between the N-H
      hydrogen and fluorine that cannot be attributed to long-range, through-bond
      interactions; the couplings correlate favorably with calculated values. The
      results obtained from these experiments are congruent with the formation of an NH
      F hydrogen bond upon protonation of 8-fluoro-N,N-dimethylnaphthalen-1-amine.

PMID- 21888335
TI  - Copper-free intramolecular alkyne-azide cycloadditions leading to seven-membered
      heterocycles.
AB  - Treatment of alk-2-ynyl derivatives of enantiopure phenylglycidol with NaN(3)
      triggers a cascade reaction consisting of stereospecific and regioselective
      epoxide ring opening followed by intramolecular azide-alkyne cycloaddition under
      strictly metal-free conditions. This simple one-pot procedure allows a fast
      buildup of molecular complexity, generating a wide array of triazolooxazepinols,
      triazolodiazepinols, and triazolothiazepinols.

PMID- 21888336
TI  - Total synthesis of (+/-)-chloranthalactone A.
AB  - A total synthesis of (+/-)-chloranthalactone A was completed. It features
      substrate-controlled epoxidation of ketone and highly diastereoselective
      intramolecular cyclopropanation to construct the cis, trans-3/5/6 tricyclic
      skeleton.

PMID- 21888337
TI  - Highly convergent synthesis of chiral bicyclophosphinates by domino
      hydrophosphinylation/Michael/Michael reaction.
AB  - Diastereoselective domino reactions of iminoalcohols and allenyl H-phosphinates
      produce chiral phosphorus bicycles in a regio- and stereoselective fashion. A
      predictive model for diastereoselection is used for these new chiral phosphinic
      esters.

PMID- 21888338
TI  - Palladium-catalyzed regioselective C-S bond cleavage of thiophenes.
AB  - Herein, a Pd-catalyzed reaction of simple and diverse bromothiophenes with
      alkynes via regioselective C-S bond activation is reported. This provides a new
      approach to prepare sulfur-based heterocycles and fulvenes.

PMID- 21888339
TI  - Synthesis of cis and trans bis-alkynyl complexes of Cr(III) and Rh(III) supported
      by a tetradentate macrocyclic amine: a spectroscopic investigation of the M(III)
      alkynyl interaction.
AB  - Alkynyl complexes of the type [M(cyclam)(CCR)(2)]OTf (where cyclam = 1,4,8,11
      tetraazacyclotetradecane; M = Rh(III) or Cr(III); and R = phenyl, 4-methylphenyl,
      4-trifluoromethylphenyl, 4-fluorophenyl, 1-naphthalenyl, 9-phenanthrenyl, and
      cyclohexyl) were prepared in 49% to 93% yield using a one-pot synthesis involving
      the addition of 2 equiv of RCCH and 4 equiv of BuLi to the appropriate
      [M(cyclam)(OTf)(2)]OTf complex in THF. The cis and trans isomers of the alkynyl
      complexes were separated using solubility differences, and the stereochemistry
      was characterized using infrared spectroscopy of the CH(2) rocking and NH bending
      region. All of the trans-[M(cyclam)(CCR)(2)]OTf complexes exhibit strong Raman
      bands between 2071 and 2109 cm(-1), ascribed to nu(s)(C=C). The stretching
      frequencies for the Cr(III) complexes are 21-28 cm(-1) lower than for the
      analogous Rh(III) complexes, a result that can be interpreted in terms of the
      alkynyl ligands acting as pi-donors. UV-vis spectra of the Cr(III) and Rh(III)
      complexes are dominated by strong charge transfer (CT) transitions. In the case
      of the Rh(III) complexes, these CT transitions obscure the metal centered (MC)
      transitions, but in the case of the Cr(III) complexes the MC transitions are
      unobscured and appear between 320 and 500 nm, with extinction coefficients (170
      700 L mol(-1) cm(-1)) indicative of intensity stealing from the proximal CT
      bands. The Cr(III) complexes show long-lived (240-327 MUs), structureless, MC
      emission centered between 731 and 748 nm in degassed room temperature aqueous
      solution. Emission characteristics are also consistent with the arylalkynyl
      ligands acting as pi-donors. The Rh(III) complexes also display long-lived (4-21
      MUs), structureless, metal centered emission centered between 524 and 548 nm in
      degassed room temperature solution (CH(3)CN).

PMID- 21888341
TI  - DFT/MM description of flavin IR spectra in BLUF domains.
AB  - A class of photoreceptors occurring in various organisms consists of domains that
      are blue light sensing using flavin (BLUF). The vibrational spectra of the flavin
      chromophore are spectroscopically well characterized for the dark-adapted resting
      states and for the light-adapted signaling states of BLUF domains in solution.
      Here we present a theoretical analysis of such spectra by applying density
      functional theory (DFT) to the flavin embedded in molecular mechanics (MM) models
      of its protein and solvent environment. By DFT/MM we calculate flavin spectra for
      seven different X-ray and NMR structures of BLUF domains occurring in the
      transcriptional antirepressor AppA and in the blue light receptor B (BlrB) of the
      purple bacterium Rb. Sphaeroides as well as in the phototaxis photoreceptor
      Slr1694 of the cyanobacterium Synechocystis. By considering the dynamical
      stabilities of associated all-atom simulation models and by comparing calculated
      with observed vibrational spectra, we show that two of the considered structures
      (both AppA) are obviously erroneous and that specific features of two further
      crystal structures (BlrB and Slr1694) cannot represent the states of the
      respective BLUF domains in solution. Thereby, the conformational transitions
      elicited by solvation are identified. In this context we demonstrate how hydrogen
      bonds of varying strengths can tune in BLUF domains the C?O stretching
      frequencies of the flavin chromophore. Furthermore we show that the DFT/MM
      spectra of the flavin calculated for two different AppA BLUF conformations, which
      are called Trp(in) and Met(in), fit very well to the spectroscopic data observed
      for the dark and light states, respectively, if (i) polarized MM force fields,
      which are calculated by an iterative DFT/MM procedure, are employed for the
      flavin binding pockets and (ii) the calculated frequencies are properly scaled.
      Although the associated analysis indicates that the Trp(in) conformation belongs
      to the dark state, no clear light vs dark distinction emerges for the Met(in)
      conformation. In this connection, a number of methodological issues relevant for
      such complex computations are thoroughly discussed showing, in particular, why
      our current descriptions could not decide the light vs dark question for Met(in).

PMID- 21888340
TI  - Effects of base polymer hydrophobicity and end-group modification on polymeric
      gene delivery.
AB  - A new 320-member polymer library of end-modified poly(beta-amino ester)s was
      synthesized. This library was chosen such that small differences to the
      structures of component backbone, side-chain, and end-group monomers could be
      systematically and simultaneously evaluated. The in vitro transfection efficacy
      and cytotoxicity of DNA nanoparticles formed from this library were assessed.
      This library approach not only enabled us to synthesize and test a large variety
      of structures rapidly but also provided us with a robust data set to analyze for
      the effect of small structural permutations to polymer chain structure. Small
      changes to the side chains, backbones, and end groups within this polymer library
      produced dramatic results, with transfection efficacy of CMV-Luc varying over 4
      orders in a 96-well plate format. Increasing hydrophobicity of the base polymer
      backbone and side chain tended to increase transfection efficacy, but the most
      hydrophobic side chains and backbones showed the least requirement for a
      hydrophobic pair. Optimal PBAE formulations were superior to commercially
      available nonviral alternatives FuGENE HD and Lipofectamine 2000, enabling ~3
      fold increased luminescence (2.2 * 10(6) RLU/well vs 8.1 * 10(5) RLU/well) and 2
      fold increased transfection percentage (76.7% vs 42.9%) as measured by flow
      cytometry with comparable or reduced toxicity.

PMID- 21888342
TI  - Controlled silanization of silica nanoparticles to stabilize foams, climbing
      films, and liquid marbles.
AB  - We describe a method for the synthesis of multigram amounts of silica
      nanoparticles which are controllably hydrophobized to different extents using a
      room temperature vapor phase silanization process. The extent of hydrophobization
      of the particles can be adjusted by changing the amount of dichlorodimethylsilane
      reagent used in the reaction. The method produces particles with good uniformity
      of surface coating; the silane coating varies from monolayer coverage at low
      extents of hydrophobization to approximately trilayer at high extents of
      hydrophobization. Acid-base titration using conductivity detection was used to
      characterize the extent of hydrophobization which is expressed as the percent of
      surface silanol groups remaining after silanization. Particles with %SiOH ranging
      from 100% (most hydrophilic) to 20% (most hydrophobic) were hand shaken with
      water/methanol mixtures and produced either a particle dispersion, foam, climbing
      films, or liquid marbles. The type of colloidal structure produced is discussed
      in terms of the liquid-air-particle contact angle and the energy of adsorption of
      the particles to the liquid-air surface.

PMID- 21888343
TI  - A manganese(V)-oxo pi-cation radical complex: influence of one-electron oxidation
      on oxygen-atom transfer.
AB  - One-electron oxidation of Mn(V)-oxo corrolazine 2 affords 2(+), the first example
      of a Mn(V)(O) pi-cation radical porphyrinoid complex, which was characterized by
      UV-vis, EPR, LDI-MS, and DFT methods. Access to 2 and 2(+) allowed for a direct
      comparison of their reactivities in oxygen-atom transfer (OAT) reactions. Both
      complexes are capable of OAT to PPh(3) and RSR substrates, and 2(+) was found to
      be a more potent oxidant than 2. Analysis of rate constants and activation
      parameters, together with DFT calculations, points to a concerted OAT mechanism
      for 2(+) and 2 and indicates that the greater electrophilicity of 2(+) likely
      plays a dominant role in enhancing its reactivity. These results are relevant to
      comparisons between Compound I and Compound II in heme enzymes.

PMID- 21888344
TI  - Understanding run-in behavior of diamond-like carbon friction and preventing
      diamond-like carbon wear in humid air.
AB  - The friction behavior of diamond-like carbon (DLC) is very sensitive to the test
      environment. For hydrogen-rich DLC tested in dry argon and hydrogen, there was
      always an induction period, so-called "run-in" period, during which the friction
      coefficient was high and gradually decreased before DLC showed an ultralow
      friction coefficient (less than 0.01) behavior. Regardless of friction
      coefficients and hydrogen contents, small amounts of wear were observed in dry
      argon, hydrogen, oxygen, and humid argon environments. Surprisingly, there were
      no wear or rubbing scar on DLC surfaces tested in n-pentanol vapor conditions,
      although the friction coefficient was relatively high among the five test
      environments. Ex situ X-ray photoelectron and near-edge X-ray absorption fine
      structure spectroscopy analyses failed to reveal any differences in chemical
      composition attributable to the environment dependence of DLC friction and wear.
      The failure of getting chemical information of oxygenated surface species from
      the ex situ analysis was found to be due to facile oxidation of the DLC surface
      upon exposure to air. The removal or wear of this surface oxide layer is
      responsible for the run-in behavior of DLC. It was discovered that the alcohol
      vapor can also prevent the oxidized DLC surface from wear in humid air
      conditions.

PMID- 21888345
TI  - Optical and photocatalytic properties of single crystalline ZnO at the air-liquid
      interface by an aminolytic reaction.
AB  - Crystalline flowerlike ZnO was synthesized by an aminolytic reaction at the air
      liquid interface in an aqueous media at an alkaline pH. A thin visible film was
      formed at the air-liquid interface by self-assembly of flowerlike ZnO.
      Diffraction studies show rearrangement of the single crystalline units at the air
      liquid interface leading to the formation of nanobelts. These nanobelts overlap
      systematically to form petals of the flowerlike structure; individual petals get
      curved with time. Each nanobelt is found to be single crystalline and can be
      indexed as the hexagonal ZnO phase. The organic product formed in the aminolytic
      reaction and dissolution-reprecipitation mechanism is the driving force for the
      formation of flowerlike ZnO at the air-liquid interface. A clear relationship
      between the surface, photocatalytic, and photoluminescent properties of ZnO is
      observed. The flowerlike structure exhibits a blue shift (3.56 eV) in the band
      emission as compared to bulk ZnO (3.37 eV). The photodegradation of methylene
      blue over the flowerlike ZnO catalyst formed at the air-liquid interface and in
      the sediments shows enhanced photocatalytic activity. The sub-bands formed due to
      surface defects facilitate separation of charge carriers increasing their
      lifetime, leading to enhanced photocatalytic activity of flowerlike ZnO.

PMID- 21888346
TI  - Fundamental examination of nanoparticle heating kinetics upon near infrared (NIR)
      irradiation.
AB  - Near infrared (NIR) light, which spans wavelengths from ~700-1100 nm holds
      particular promise in bionanotechnology-enabled applications because both NIR
      light and nanoparticles (NPs) have the potential for remote activation leading to
      exquisite localization and targeting scenarios. In this study, aqueous solutions
      of carbon and metal-based NPs (carbon black, single-walled carbon nanotubes,
      silver nanoparticles and copper nanoparticles) were exposed to continuous NIR
      laser (lambda = 1064 nm) irradiation at powers of 2.2W and 4.5W. The differential
      heating of bulk aqueous suspension of NPs with varying physicochemical properties
      revealed maximum temperatures of 67  degrees C with visible evidence of
      condensation and bubble formation. The basis of the NP heating is due to the
      strong intrinsic optical absorbance in the NIR spectral window and the
      transduction of this NIR photon energy into thermal energy. In this regard, UV
      vis measurements can accurately predict NP heating kinetics prior to NIR
      irradiation. Further, a uniform thermodynamic heating model demonstrates close
      agreement with the experimental data for the low NIR-absorbing NPs. However, the
      uniform thermodynamic heating model used in this study does not accurately
      portray the energy release upon localized NP heating because of bubble formation
      for the highly absorbing NPs. Therefore, this study reveals the differential
      heating kinetics of NPs excited with NIR with implications in the development of
      novel NIR-NP-based systems.

PMID- 21888347
TI  - Toward mechanistic understanding of nuclear reprocessing chemistries by
      quantifying lanthanide solvent extraction kinetics via microfluidics with
      constant interfacial area and rapid mixing.
AB  - The closing of the nuclear fuel cycle is an unsolved problem of great importance.
      Separating radionuclides produced in a nuclear reactor is useful both for the
      storage of nuclear waste and for recycling of nuclear fuel. These separations can
      be performed by designing appropriate chelation chemistries and liquid-liquid
      extraction schemes, such as in the TALSPEAK process (Trivalent Actinide
      Lanthanide Separation by Phosphorus reagent Extraction from Aqueous Komplexes).
      However, there are no approved methods for the industrial scale reprocessing of
      civilian nuclear fuel in the United States. One bottleneck in the design of next
      generation solvent extraction-based nuclear fuel reprocessing schemes is a lack
      of interfacial mass transfer rate constants obtained under well-controlled
      conditions for lanthanide and actinide ligand complexes; such rate constants are
      a prerequisite for mechanistic understanding of the extraction chemistries
      involved and are of great assistance in the design of new chemistries. In
      addition, rate constants obtained under conditions of known interfacial area have
      immediate, practical utility in models required for the scaling-up of laboratory
      scale demonstrations to industrial-scale solutions. Existing experimental
      techniques for determining these rate constants suffer from two key drawbacks:
      either slow mixing or unknown interfacial area. The volume of waste produced by
      traditional methods is an additional, practical concern in experiments involving
      radioactive elements, both from disposal cost and experimenter safety
      standpoints. In this paper, we test a plug-based microfluidic system that uses
      flowing plugs (droplets) in microfluidic channels to determine absolute
      interfacial mass transfer rate constants under conditions of both rapid mixing
      and controlled interfacial area. We utilize this system to determine, for the
      first time, the rate constants for interfacial transfer of all lanthanides, minus
      promethium, plus yttrium, under TALSPEAK process conditions, as a first step
      toward testing the molecular mechanism of this separation process.

PMID- 21888348
TI  - Theoretical study of absorption and emission properties of green and yellow
      emitting iridium(III) complexes.
AB  - Iridium(III) complexes are among the most used phosphorescent materials for the
      development of organic light emitting diodes (OLEDs). In this work, the
      photophysical properties of a family of complexes based on phenyldiazine ligands
      were studied. Their ground state geometric and electronic structures as well as
      their absorption and emission spectra were investigated by the means of density
      functional theory (DFT) and time-dependent DFT (TD-DFT). An extremely good
      agreement between the computed and experimental values is obtained, thus
      suggesting that the computational protocol here applied could be used for the in
      silico screening and design of new Ir-based emitting complexes.

PMID- 21888349
TI  - Vibrational characterization of L-leucine phosphonate analogues: FT-IR, FT-Raman,
      and SERS spectroscopy studies and DFT calculations.
AB  - This study reports the Raman (FT-Raman) and absorption infrared (FT-IR) spectra,
      based on calculated wavenumbers and normal modes of vibrations, of the following
      compounds: L-Leu-D-NH-CH(Me)-PO(3)H(2) (LI), L-Leu-NH-C(Me)(2)-PO(3)H(2) (LII), L
      Leu-D-NH-CH(Et)-PO(3)H(2) (LIII), L-Leu-L-NH-CH(Et)-PO(3)H(2) (LIV), L-Leu-L-NH
      CH(EtOH)-PO(3)H(2) (LV), L-Leu-NH-C(Me)(Et)-PO(3)H(2) (LVI), L-Leu-L-NH-CH(PrA)
      PO(3)H(2) (LVII), L-Leu-L-NH-CH(c-Pr)-PO(3)H(2) (LVIII), L-Leu-L-NH-CH(t-Bu)
      PO(3)H(2) (LIX), L-Leu-L-NH-CH(BuA)-PO(3)H(2) (LX), L-Leu-L-NH-CH(c-Bu)-PO(3)H(2)
      (LXI), and L-Leu-L-NH-C(Adm)-PO(3)H(2) (LXII). The equilibrium geometries and
      vibrational wavenumbers were calculated using density functional theory (DFT) at
      the B3LYP, 6-311++G** level using Gaussian 03, Raint, GaussSum 0.8, and Gar2ped
      software. We briefly compare and analyze the experimental and calculated
      vibrational wavenumbers in the range 4000-400 cm(-1). In addition, the Raman
      wavenumbers are compared to those from the surface-enhanced Raman scattering
      (SERS) spectra for the phosphono analogues of l-leucine (l-Leu) adsorbed on a
      colloidal silver surface in an aqueous solution. The geometries of these
      molecules etched on the silver surface were deduced from observed changes in both
      the intensity and broadness of Raman bands in the spectra of the bound versus
      free species. For example, LVI appears to adsorb onto the colloidal silver
      particles mainly through the amine group and amide bond, which assists in the
      adsorption process, whereas LII shows strongly enhanced SERS bands due to the
      rocking, twisting, and stretching vibrations of the N(amid)C(sg)(Me)(2)P
      fragment, suggesting that this peptide's interaction with the silver surface
      occurs mainly via this fragment. On the other hand, the most dominant SERS bands
      of LIII and LIV due to the P?O bond stretches reflect P?O...Ag complex formation.

PMID- 21888351
TI  - ReaxFF-lg: correction of the ReaxFF reactive force field for London dispersion,
      with applications to the equations of state for energetic materials.
AB  - The practical levels of density functional theory (DFT) for solids (LDA, PBE,
      PW91, B3LYP) are well-known not to account adequately for the London dispersion
      (van der Waals attraction) so important in molecular solids, leading to
      equilibrium volumes for molecular crystals ~10-15% too high. The ReaxFF reactive
      force field is based on fitting such DFT calculations and suffers from the same
      problem. In the paper we extend ReaxFF by adding a London dispersion term with a
      form such that it has low gradients (lg) at valence distances leaving the already
      optimized valence interactions intact but behaves as 1/R(6) for large distances.
      We derive here these lg corrections to ReaxFF based on the experimental crystal
      structure data for graphite, polyethylene (PE), carbon dioxide, and nitrogen and
      for energetic materials: hexahydro-1,3,5-trinitro-1,3,5-s-triazine (RDX),
      pentaerythritol tetranitrate (PETN), 1,3,5-triamino-2,4,6-trinitrobenzene (TATB),
      and nitromethane (NM). After this dispersion correction the average error of
      predicted equilibrium volumes decreases from 18.5 to 4.2% for the above systems.
      We find that the calculated crystal structures and equation of state with ReaxFF
      lg are in good agreement with experimental results. In particular, we examined
      the phase transition between alpha-RDX and gamma-RDX, finding that ReaxFF-lg
      leads to excellent agreement for both the pressure and volume of this transition
      occurring at ~4.8 GPa and ~2.18 g/cm(3) density from ReaxFF-lg vs 3.9 GPa and
      ~2.21 g/cm(3) from experiment. We expect ReaxFF-lg to improve the descriptions of
      the phase diagrams for other energetic materials.

PMID- 21888350
TI  - Smart multifunctional nanostructure for targeted cancer chemotherapy and magnetic
      resonance imaging.
AB  - Targeted chemotherapy and magnetic resonance imaging of cancer cells in vitro has
      been achieved using a smart multifunctional nanostructure (SMN) constructed from
      a porous hollow magnetite nanoparticle (PHMNP), a heterobifunctional PEG ligand,
      and an aptamer. The PHMNPs were prepared through a three-step reaction and loaded
      with the anticancer drug doxorubicin while being functionalized with PEG ligands.
      Targeting aptamers were then introduced by reaction with the PEG ligands. The
      pores of the PHMNPs are stable at physiological pH, but they are subject to acid
      etching. Specific binding and uptake of the SMN to the target cancer cells
      induced by aptamers was observed. In addition, multiple aptamers on the surface
      of one single SMN led to enhanced binding and uptake to target cancer cells due
      to the multivalent effect. Upon reaching the lysosomes of target cancer cells
      through receptor-mediated endocytosis, the relatively low lysosomal pH level
      resulted in corrosion of the PHMNP pores, facilitating the release of doxorubicin
      to kill the target cancer cells. In addition, the potential of using SMN for
      magnetic resonance imaging was also investigated.

PMID- 21888352
TI  - Role of the somersault rearrangement in the oxidation step for flavin
      monooxygenases (FMO). A comparison between FMO and conventional xenobiotic
      oxidation with hydroperoxides.
AB  - Model quantum mechanical calculations presented for C-4a-flavin hydroperoxide
      (FlHOOH) at the B3LYP/6-311+G(d,p) level suggest a new mechanism for flavoprotein
      monooxygenase (FMO) oxidation involving a concerted homolytic O-O bond cleavage
      in concert with hydroxyl radical transfer from the flavin hydroperoxide rather
      than an S(N)2-like displacement by the substrate on the C-4a-hydroperoxide OOH
      group. Homolytic O-O bond cleavage in a somersault-like rearrangement of
      hydroperoxide C-4a-flavinhydroperoxide (1) (FLHO-OH -> FLHO...HO) produces an
      internally hydrogen-bonded HO(*) radical intermediate with a classical activation
      barrier of 27.0 kcal/mol. Model hydroperoxide 1 is used to describe the
      transition state for the key oxidation step in the paradigm aromatic hydroxylase,
      p-hydroxybenzoate hydroxylase (PHBH). A comparison of the electron distribution
      in the transition structures for the PHBH hydroxylation of p-hydroxybenzoic acid
      (DeltaE(?) = 23.0 kcal/mol) with that of oxidation of trimethylamine (DeltaE(?) =
      22.3 kcal/mol) and dimethyl sulfide (DeltaE? = 14.1 kcal/mol) also suggests a
      mechanism involving a somersault mechanism in concert with transfer of an HO(*)
      radical to the nucleophilic heteroatom center with a hydrogen transfer back to
      the FLH-O residue after the barrier is crossed to produce the final product, FLH
      OH. In each case the hydroxylation barrier was less than that of the O-O
      rearrangement barrier in the absence of a substrate supporting an overall
      concerted process. All three transition structures bear a resemblance to the TS
      for the comparable hydroxylation of isobutane (DeltaE(?) = 29.2 kcal/mol) and for
      simple Fenton oxidation by aqueous iron(III) hydroperoxides. To our surprise the
      oxidation of N- and S-nucleophiles with conventional oxidants such as alkyl
      hydroperoxides and peracids also proceeds by HO(*) radical transfer in a manner
      quite similar to that for tricyclic hydroperoxide 1. Stabilization of the
      developing oxyradical produced by somersault rearrangement for concerted
      enzymatic oxidation with tricyclic hydroperoxide 1 results in a reduced overall
      activation barrier.

PMID- 21888353
TI  - The original Michaelis constant: translation of the 1913 Michaelis-Menten paper.
AB  - Nearly 100 years ago Michaelis and Menten published their now classic paper
      [Michaelis, L., and Menten, M. L. (1913) Die Kinetik der Invertinwirkung.
      Biochem. Z. 49, 333-369] in which they showed that the rate of an enzyme
      catalyzed reaction is proportional to the concentration of the enzyme-substrate
      complex predicted by the Michaelis-Menten equation. Because the original text was
      written in German yet is often quoted by English-speaking authors, we undertook a
      complete translation of the 1913 publication, which we provide as  Supporting
      Information . Here we introduce the translation, describe the historical context
      of the work, and show a new analysis of the original data. In doing so, we
      uncovered several surprises that reveal an interesting glimpse into the early
      history of enzymology. In particular, our reanalysis of Michaelis and Menten's
      data using modern computational methods revealed an unanticipated rigor and
      precision in the original publication and uncovered a sophisticated,
      comprehensive analysis that has been overlooked in the century since their work
      was published. Michaelis and Menten not only analyzed initial velocity
      measurements but also fit their full time course data to the integrated form of
      the rate equations, including product inhibition, and derived a single global
      constant to represent all of their data. That constant was not the Michaelis
      constant, but rather V(max)/K(m), the specificity constant times the enzyme
      concentration (k(cat)/K(m) * E(0)).

PMID- 21888354
TI  - Volatile organic compounds in small- and medium-sized commercial buildings in
      California.
AB  - While small- and medium-sized commercial buildings (SMCBs) make up 96% of the
      commercial buildings in the U.S., serving a large variety of uses, little
      information is available on indoor air quality (IAQ) in SMCBs. This study
      investigated 37 SMCBs distributed across different sizes, ages, uses, and regions
      of California. We report indoor concentrations and whole building emission rates
      of a suite of 30 VOCs and aldehydes in these buildings. There was a considerable
      range in the concentrations for each of the contaminants, especially for
      formaldehyde, acetaldehyde, decamethylcyclopentasiloxane, d-limonene, 2
      butoxyethanol, toluene, 2,2,4-trimethylpentanediol diisobutyrate, and
      diethylphthalate. The cause of higher concentrations in some building categories
      generally corresponded to expected sources, for example, chloroform was higher in
      restaurants and grocery stores, and formaldehyde was higher in retail stores and
      offices. Factor analysis suggests sources in SMCBs include automobile/traffic,
      cleaning products, occupant sources, wood products/coating, and plasticizers. The
      comparison to health guidelines showed that formaldehyde concentrations were
      above the chronic RELs required by the OEHHA (9 MUg/m3) in 86% of the buildings.
      Data collected in this study begins to fill the knowledge gap for IAQ in SMCBs
      and helps us understand the indoor sources of VOCs to further improve indoor air
      quality in SMCBs.

PMID- 21888355
TI  - A general approach to controlling the surface composition of poly(ethylene oxide)
      based block copolymers for antifouling coatings.
AB  - To control the surface properties of a polystyrene-block-poly(ethylene oxide)
      diblock copolymer, perfluorinated chemical moieties were specifically
      incorporated into the block copolymer backbone. A polystyrene-block
      poly[(ethylene oxide)-stat-(allyl glycidyl ether)] [PS-b-P(EO-stat-AGE)]
      statistical diblock terpolymer was synthesized with varying incorporations of
      allyl glycidyl ether (AGE) in the poly(ethylene oxide) block from 0 to 17 mol %.
      The pendant alkenes of the AGE repeat units were subsequently functionalized by
      thiol-ene chemistry with 1H,1H,2H,2H-perfluorooctanethiol, yielding fluorocarbon
      functionalized AGE (fAGE) repeat units. (1)H NMR spectroscopy and size-exclusion
      chromatography indicated well-defined structures with complete functionalization
      of the pendant alkenes. The surfaces of the polymer films were characterized
      after spray coating by X-ray photoelectron spectroscopy (XPS) and near-edge X-ray
      absorption fine structure spectroscopy (NEXAFS), showing that the P(EO-stat-fAGE)
      block starts to compete with polystyrene to populate the surface after only 1 mol
      % incorporation of fAGE. Increasing the incorporation of fAGE led to an increased
      amount of perfluorocarbons on the surface and a decrease in the concentration of
      PS. At a fAGE incorporation of 8 mol %, PS was not detected at the surface, as
      measured by NEXAFS spectroscopy. Water contact angles measured by the captive-air
      bubble technique showed the underwater surfaces to be dynamic, with advancing and
      receding contact angles varying by >20 degrees . Protein adsorption studies
      demonstrated that the fluorinated surfaces effectively prevent nonspecific
      binding of proteins relative to an unmodified PS-b-PEO diblock copolymer. In
      biological systems, settlement of spores of the green macroalga Ulva was
      significantly lower for the fAGE-incorporated polymers compared to the unmodified
      diblock and a polydimethylsiloxane elastomer standard. Furthermore, the
      attachment strength of sporelings (young plants) of Ulva was also reduced for the
      fAGE-containing polymers, affirming their potential as fouling-release coatings.

PMID- 21888356
TI  - Preparation, characteristics, and stability of glutathione-loaded nanoparticles.
AB  - The aim of this study was to investigate the characteristics and oxidative
      stability of chitosan-glutathione conjugate (CS-GSH) and CS-GSH nanoparticles (CS
      GSH NPs) to explore the potentials of these nanoparticle systems for GSH
      delivery. CS-GSH was synthesized using a radical polymerization method, and CS
      GSH NP was prepared by ionic gelation of CS-GSH with sodium tripolyphosphate
      (TPP). The sizes of CS-GSH NPs significantly increased with increasing CS-GSH
      concentration and CS-GSH/TPP ratio. The entrapment efficiency (EE) significantly
      increased with increasing CS-GSH concentration and significantly decreased with
      increasing CS-GSH/TPP ratio. The immobilized GSH could be protected against
      oxidation compared to free GSH. The thiol content in the nanoencapsulated GSH was
      more effectively maintained than those in free GSH and CS-GSH, regardless of the
      presence of oxidative stress-inducing agents. These results suggest that CS-GSH
      NP can be used to enhance the oxidative stability of GSH.

PMID- 21888357
TI  - Monomeric fullerenes in lipid membranes: effects of molecular shape and polarity.
AB  - We report a combined theoretical and experimental study on the single-molecule
      interaction of fullerenes with phospholipid membranes. We studied pristine C(60)
      (1) and two N-substituted fulleropyrrolidines (2 and 3), one of which (3) bore a
      paramagnetic nitroxide group. Theoretical predictions of fullerene distribution
      and permeability across lipid bilayers were combined with electron paramagnetic
      resonance (EPR) experiments in aligned DMPC/DHPC bicelles containing the
      paramagnetic fulleropyrrolidine 3 or either one of the diamagnetic fullerenes
      together with spin-labeled lipids. We found that, at low concentrations,
      fullerenes are present in the bilayer as single molecules. Their preferred
      location in the membrane is only slightly influenced by the derivatization: all
      derivatives were confined just below the hydrophilic/hydrophobic interface,
      because of the key role played by dispersion interactions between the highly
      polarizable fullerene cage and the hydrocarbon chains, which are especially tight
      within this region. However, the deviation from spherical shape is sufficient to
      induce a preferential orientation of 2 and 3 in the membrane. We predict that
      monomeric fullerenes spontaneously penetrate the bilayer, in agreement with the
      results of molecular dynamics simulations, but we point out the limits of the
      currently used permeability model when applied to hydrophobic solutes.

PMID- 21888359
TI  - Unusually stable aqueous lyotropic gyroid phases from gemini dicarboxylate
      surfactants.
AB  - Aqueous lyotropic liquid crystal (LLC) assemblies with bicontinuous cubic
      morphologies (Q-phases) have shown promise in applications ranging from selective
      chemical separations to ion transporting media, yet universal design criteria for
      amphiphiles that adopt these unique structures remain elusive. Recent reports
      have demonstrated that cationic gemini surfactants exhibit a tendency to form
      bicontinuous cubic LLCs as compared to single-tail amphiphiles; however, the
      universality of this surfactant design motif in stabilizing Q-phases remains
      untested. Herein, we report the modular synthesis of a new class of anionic
      gemini surfactants derived from aliphatic carboxylic acids and demonstrate their
      unexpectedly strong propensity to form gyroid LLC phases with unprecedented
      stability between 25 and 100  degrees C over amphiphile concentration windows up
      to 20 wt % wide. By systematically varying the alkyl spacer length and surfactant
      counterions (Na(+), K(+), and (CH(3))(4)N(+)), we identify molecular motifs that
      favor formation of technologically useful bicontinuous cubic LLC morphologies.

PMID- 21888360
TI  - Theoretical prediction on the thermal stability of cyclic ozone and strong oxygen
      tunneling.
AB  - Dual-level dynamics calculation with variational transition state theory
      including multidimensional tunneling has been performed on the isomerization
      reaction of cyclic ozone -> normal (open) ozone, which was believed to be the
      stability-determining reaction of the elusive cyclic ozone molecule under thermal
      condition. The high-level potential energy surface data were obtained from the
      calculation using the MRCISD+Q theory with the aug-cc-pVQZ basis set, while the
      low-level reaction path information was obtained using the hybrid density
      functional theory B3LYP with the cc-pVTZ basis set. The calculated results showed
      very significant tunneling effects below 300 K (a factor of ~200 at 300 K and
      over 10(7) at 200 K). Because of the strong tunneling effects and the potential
      energy surface crossing of the 1A(1) and 1A(2) states, the isomerization
      reactions were found to be significantly faster than previously believed. The
      half-life of the cyclic ozone was estimated only ~10 s at 200 K and ~70 s below
      100 K, which might partly explain the unsuccessful attempts for its experimental
      identification. The kinetic isotope effects (KIEs) for various (18)O substitution
      reactions were also calculated as a function of temperature and were as high as
      10 at very low temperature. Because of the large KIEs, the experimental
      identification of the cyclic (18)O(3) seems more promising.

PMID- 21888358
TI  - The N-terminal domain of the Escherichia coli PriA helicase contains both the DNA
      and nucleotide-binding sites. Energetics of domain--DNA interactions and
      allosteric effect of the nucleotide cofactors.
AB  - Functional interactions of the Escherichia coli PriA helicase 181N-terminal
      domain with the DNA and nucleotide cofactors have been quantitatively examined.
      The isolated 181N-terminal domain forms a stable dimer in solution, most probably
      reflecting the involvement of the domain in specific cooperative interactions of
      the intact PriA protein--double-stranded DNA (dsDNA) complex. Only one monomer of
      the domain dimer binds the DNA; i.e., the dimer has one effective DNA-binding
      site. Although the total site size of the dimer--single-stranded DNA (ssDNA)
      complex is ~13 nucleotides, the DNA-binding subsite engages in direct
      interactions with approximately five nucleotides. A small number of interacting
      nucleotides indicates that the DNA-binding subsites of the PriA helicase, i.e.,
      the strong subsite on the helicase domain and the weak subsite on the N-terminal
      domain, are spatially separated in the intact enzyme. Contrary to current views,
      the subsite has an only slight preference for the 3'-end OH group of the ssDNA
      and lacks any significant base specificity, although it has a significant dsDNA
      affinity. Unlike the intact helicase, the DNA-binding subsite of the isolated
      domain is in an open conformation, indicating the presence of the direct helicase
      domain--N-terminal domain interactions. The discovery that the 181N-terminal
      domain possesses a nucleotide-binding site places the allosteric, weak nucleotide
      binding site of the intact PriA on the N-terminal domain. The specific effect of
      ADP on the domain DNA-binding subsite indicates that in the intact helicase, the
      bound ADP not only opens the DNA-binding subsite but also increases its intrinsic
      DNA affinity.

PMID- 21888361
TI  - Aryl trihydroxyborate salts: thermally unstable species with unusual gelation
      abilities.
AB  - A series of aryl trihydroxyborate salts were synthesized and found to form gels
      in benzene. The compounds were thermally unstable and readily underwent
      protodeboronation in solution and the solid state. Gelation could be induced
      without decomposition via sonication. Subsequent characterization studies
      revealed an unusual dependence of gel properties on alkyl chain length.

PMID- 21888363
TI  - Predicting two-dimensional boron-carbon compounds by the global optimization
      method.
AB  - We adopt a global optimization method to predict two-dimensional (2D)
      nanostructures through the particle-swarm optimization (PSO) algorithm. By
      performing PSO simulations, we predict new stable structures of 2D boron-carbon
      (B-C) compounds for a wide range of boron concentrations. Our calculations show
      that: (1) All 2D B-C compounds are metallic except for BC(3) which is a magic
      case where the isolation of carbon six-membered ring by boron atoms results in a
      semi-conducting behavior. (2) For C-rich B-C compounds, the most stable 2D
      structures can be viewed as boron doped graphene structures, where boron atoms
      typically form 1D zigzag chains except for BC(3) in which boron atoms are
      uniformly distributed. (3) The most stable 2D structure of BC has alternative
      carbon and boron ribbons with strong in-between B-C bonds, which possesses a high
      thermal stability above 2000 K. (4) For B-rich 2D B-C compounds, there is a novel
      planar-tetracoordinate carbon motif with an approximate C(2)(v) symmetry.

PMID- 21888362
TI  - Cross-coupling of mesylated phenol derivatives with potassium
      cyclopropyltrifluoroborate.
AB  - C-O activation of mesylates by a palladium catalyst and subsequent cross-coupling
      with potassium cyclopropyltrifluoroborate have been achieved with high yield.
      Both electron-enriched and electron-deficient aryl mesylates are suitable
      electrophilic partners for the Suzuki-Miyaura reaction. The scope was
      successfully extended to heteroaryl mesylates with yields up to 94%.

PMID- 21888364
TI  - Fibronectin and bone morphogenetic protein-2-decorated poly(OEGMA-r-HEMA) brushes
      promote osseointegration of titanium surfaces.
AB  - To be better used as medical implants in orthopedic and dental clinical
      applications, titanium and titanium-based alloys need to be capable of inducing
      osteogenesis. Here we describe a method that allows the facile decoration of
      titanium surfaces to impart an osteogenesis capacity. A Ti surface was first
      deposited on a poly(OEGMA-r-HEMA) film using surface-initiated atom-transfer
      radical polymerization (SI-ATRP) with the further step of carboxylation. The
      modified surfaces were resistant to cell adhesion. Fibronectin (FN) and
      recombinant human bone morphogenetic protein-2 (rhBMP-2) were further immobilized
      onto p(OEGMA-r-HEMA) matrices. Our results demonstrate that the FN- and rhBMP-2
      conjugated polymer surfaces could induce the adhesion of MC3T3 cells on Ti
      surfaces. Moreover, the protein-tethered surface exhibited enhanced cell
      differentiation in terms of alkaline phosphatase activity compared to that of the
      pristine Ti surface at similar cell proliferation rates. This research
      establishes a simple modification method of Ti surfaces via Ti-thiolate self
      assembled monolayers (SAMs) and SI-ATRP and identifies a dual-functional Ti
      surface that combines antifouling and osseointegration promotion.

PMID- 21888365
TI  - Computational studies of lithium diisopropylamide deaggregation.
AB  - Density functional theory computations [MP2/6-31G(d)//B3LYP/6-31G(d)] on the
      deaggregation of lithium diisopropylamide (LDA) dimer solvated by two
      tetrahydrofuran ligands to give the corresponding trisolvated monomer show eight
      structurally distinct minima. The barriers to exchange are comparable to those
      expected from experimental studies showing rate-limiting deaggregations. The role
      of conformational isomerism in deaggregation and the extent that deaggregation
      rates dictate LDA reactivity under synthetically important conditions are
      considered.

PMID- 21888366
TI  - Anion binding by bambus[6]uril probed in the gas phase and in solution.
AB  - Electrospray ionization mass spectrometry (ESI-MS) is used to probe the binding
      of small anions to the macrocycle of bambus[6]uril. For the halide ions, the
      experimental patterns suggest F(-) < Cl(-) < Br(-) < I(-), which is consistent
      with the order of anion binding found in the condensed phase. Parallel
      equilibrium studies in the condensed phase establish the association constants of
      halide anions and bambus[6]uril in mixed solvents. A detailed analysis of the
      mass spectrometric data is used to shed light on the correlations between the
      binding constants in the condensed phase and the ion abundances observed using
      ESI-MS. From the analysis it becomes apparent that ESI-MS can indeed represent
      the situation in solution to some extent, but the sampling in the gas-phase
      experiment is not 1:1 compared to that in solution.

PMID- 21888367
TI  - Interaction of metal ions with biomolecular ligands: how accurate are calculated
      free energies associated with metal ion complexation?
AB  - To address fundamental questions in bioinorganic chemistry, such as metal ion
      selectivity, accurate computational protocols for both the gas-phase association
      of metal-ligand complexes and solvation/desolvation energies of the species
      involved are needed. In this work, we attempt to critically evaluate the
      performance of the ab initio and DFT electronic structure methods available and
      recent solvation models in calculations of the energetics associated with metal
      ion complexation. On the example of five model complexes
      ([M(II)(CH(3)S)(H(2)O)](+), [M(II)(H(2)O)(2)(H(2)S)(NH(3))](2+),
      [M(II)(CH(3)S)(NH(3))(H(2)O)(CH(3)COO)], [M(II)(H(2)O)(3)(SH)(CH(3)COO)(Im)],
      [M(II)(H(2)S)(H(2)O)(CH(3)COO)(PhOH)(Im)](+) in typical coordination geometries)
      and four metal ions (Fe(2+), Cu(2+), Zn(2+), and Cd(2+); representing open- and
      closed-shell and the first- and second-row transition metal elements), we provide
      reference values for the gas-phase complexation energies, as presumably obtained
      using the CCSD(T)/aug-cc-pVTZ method, and compare them with cheaper methods, such
      as DFT and RI-MP2, that can be used for large-scale calculations. We also discuss
      two possible definitions of interaction energies underlying the theoretically
      predicted metal-ion selectivity and the effect of geometry optimization on these
      values. Finally, popular solvation models, such as COSMO-RS and SMD, are used to
      demonstrate whether quantum chemical calculations can provide the overall free
      enthalpy (DeltaG) changes in the range of the expected experimental values for
      the model complexes or match the experimental stability constants in the case of
      three complexes for which the experimental data exist. The data presented
      highlight several intricacies in the theoretical predictions of the experimental
      stability constants: the covalent character of some metal-ligand bonds (e.g.,
      Cu(II)-thiolate) causing larger errors in the gas-phase complexation energies,
      inaccuracies in the treatment of solvation of the charged species, and
      difficulties in the definition of the reference state for Jahn-Teller unstable
      systems (e.g., [Cu(H(2)O)(6)](2+)). Although the agreement between the
      experimental (as derived from the stability constants) and calculated values is
      often within 5 kcal.mol(-1), in more complicated cases, it may exceed 15
      kcal.mol(-1). Therefore, extreme caution must be exercised in assessing the
      subtle issues of metal ion selectivity quantitatively.

PMID- 21888368
TI  - Origin of giant ionic currents in carbon nanotube channels.
AB  - Fluid flow inside carbon nanotubes is remarkable: transport of water and gases is
      nearly frictionless, and the small channel size results in selective transport of
      ions. Very recently, devices have been fabricated in which one narrow single
      walled carbon nanotube spans a barrier separating electrolyte reservoirs. Ion
      current through these devices is about 2 orders of magnitude larger than
      predicted from the bulk resistivity of the electrolyte. Electroosmosis can drive
      these large excess currents if the tube both is charged and transports anions or
      cations preferentially. By building a nanofluidic field-effect transistor with a
      gate electrode embedded in the fluid barrier, we show that the tube carries a
      negative charge and the excess current is carried by cations. The magnitude of
      the excess current and its control by a gate electrode are correctly predicted by
      the Poisson-Nernst-Planck-Stokes equations.

PMID- 21888369
TI  - PsoP1, a milk-clotting aspartic peptidase from the basidiomycete fungus
      Piptoporus soloniensis.
AB  - The first enzyme of the basidiomycete Piptoporus soloniensis, a peptidase
      (PsoP1), was characterized after isolation from submerged cultures, purification
      by fractional precipitation, and preparative native-polyarylamide gel
      electrophoresis (PAGE). The native molecular mass of PsoP1 was 38 kDa with an
      isoelectric point of 3.9. Similar to chymosin from milk calves, PsoP1 showed a
      maximum milk-clotting activity (MCA) at 35-40  degrees C and was most stable at
      pH 6 and below 40  degrees C. The complete inhibition by pepstatin A identified
      this enzyme as an aspartic peptidase. Electrospray ionization-tandem MS showed an
      amino acid partial sequence that was more homologous to mammalian milk clotting
      peptidases than to the chymosin substitute from a fungal species, such as the
      Zygomycete Mucor miehei. According to sodium dodecyl sulfate-PAGE patterns, the
      peptidase cleaved kappa-casein in a way similar to chymosin and hydrolyzed beta
      casein slowly, as it would be expected from an efficient chymosin substitute.

PMID- 21888370
TI  - Laboratory-scale production of 13C-labeled lycopene and phytoene by bioengineered
      Escherichia coli.
AB  - Consumption of tomato products has been associated with decreased risks of
      chronic diseases such as cardiovascular disease and cancer, and therefore the
      biological functions of tomato carotenoids such as lycopene, phytoene, and
      phytofluene are being investigated. To study the absorption, distribution,
      metabolism, and excretion of these carotenoids, a bioengineered Escherichia coli
      model was evaluated for laboratory-scale production of stable isotope-labeled
      carotenoids. Carotenoid biosynthetic genes from Enterobacter agglomerans were
      introduced into the BL21Star(DE3) strain to yield lycopene. Over 96% of
      accumulated lycopene was in the all-trans form, and the molecules were highly
      enriched with 13C by 13C-glucose dosing. In addition, error-prone PCR was used to
      disrupt phytoene desaturase (crtI) function and create a phytoene-accumulating
      strain, which was also found to maintain the transcription of phytoene synthase
      (crtB). Phytoene molecules were also highly enriched with 13C when the 13C
      glucose was the only carbon source. The development of this production model will
      provide carotenoid researchers a source of labeled tracer materials to further
      investigate the metabolism and biological functions of these carotenoids.

PMID- 21888372
TI  - Base-catalyzed Povarov reaction: an unusual [1,3] sigmatropic rearrangement to
      dihydropyrimidobenzimidazoles.
AB  - A novel base-catalyzed Povarov reaction of arylamines, aldehydes, and electron
      deficient dienophiles has been developed. An unprecedented in situ [1,3]
      sigmatropic rearrangement leading to 4,10-dihydropyrimido[1,2-a]benzimidazoles
      has also been discovered. An insight of the plausible mechanism is discussed and
      supported by X-ray crystal study. This cascade reaction is achieved in a one-pot
      multicomponent fashion on soluble support under microwave conditions.

PMID- 21888371
TI  - NRPS substrate promiscuity diversifies the xenematides.
AB  - Xenematide, a cyclic depsipeptide antibiotic produced by Xenorhabdus nematophila,
      had a candidate nonribosomal peptide synthetase (NRPS) with atypical features.
      Differential metabolite analysis between a mutant and wildtype validated that
      this stand-alone NRPS was required for xenematide production, and further
      analysis led to a series of new xenematide derivatives encoded by the same NRPS.
      Our results indicate that adenylation domain promiscuity and relaxed downstream
      processing in the X. nematophila NRPS provide a conduit for xenematide
      diversification.

PMID- 21888373
TI  - Ultrahigh-performance liquid chromatographic-tandem mass spectrometric
      multimycotoxin method for quantitating 26 mycotoxins in maize silage.
AB  - A multianalyte method was developed to identify and quantitate 26 mycotoxins
      simultaneously in maize silage by means of ultrahigh-performance liquid
      chromatography-tandem mass spectrometry (UHPLC-MS/MS). The extraction and cleanup
      procedure consists of two extraction steps followed by purification on a Waters
      Oasis HLB column. The method developed was validated with the requirements of
      Commission Decision 2002/657/EC taken into account. The limit of detection and
      quantitation ranges were 5-348 and 11-695 ng/g, respectively. Apparent recovery
      varied between 61 and 116%, whereas repeatability and reproducibility were within
      the ranges of 3-45 and 5-49%, respectively. The method developed was successfully
      applied for maize silage samples taken at the cutting surface and 1 m behind that
      surface. Mainly Fusarium toxins (beauvericin, deoxynivalenol, enniatins,
      fumonisins, fusaric acid, and zearalenone) were detected, but postharvest toxins
      such as mycophenolic acid and roquefortine C were identified as well.

PMID- 21888374
TI  - A "carbonizing dragon": China's fast growing CO2 emissions revisited.
AB  - China's annual CO(2) emissions grew by around 4 billion tonnes between 1992 and
      2007. More than 70% of this increase occurred between 2002 and 2007. While
      growing export demand contributed more than 50% to the CO(2) emission growth
      between 2002 and 2005, capital investments have been responsible for 61% of
      emission growth in China between 2005 and 2007. We use structural decomposition
      analysis to identify the drivers for China's emission growth between 1992 and
      2007, with special focus on the period 2002 to 2007 when growth was most rapid.
      In contrast to previous analysis, we find that efficiency improvements have
      largely offset additional CO(2) emissions from increased final consumption
      between 2002 and 2007. The strong increases in emissions growth between 2002 and
      2007 are instead explained by structural change in China's economy, which has
      newly emerged as the third major emission driver. This structural change is
      mainly the result of capital investments, in particular, the growing prominence
      of construction services and their carbon intensive supply chain. By closing the
      model for capital investment, we can now show that the majority of emissions
      embodied in capital investment are utilized for domestic household and government
      consumption (35-49% and 19-36%, respectively) with smaller amounts for the
      production of exports (21-31%). Urbanization and the associated changes in
      lifestyle are shown to be more important than other socio-demographic drivers
      like the decreasing household size or growing population. We argue that
      mitigation efforts will depend on the future development of these key drivers,
      particularly capital investments which dictate future mitigation costs.

PMID- 21888375
TI  - Halogen bonding interaction between fluorohalides and isocyanides.
AB  - The optimized geometries and corresponding binding energies of complexes between
      fluorohalides, FX (X = Cl, Br, and I), and isocyanides, CNY (Y = CN, NC, NO(2),
      F, CF(3), Cl, Br, H, CCF, CCH, CH(3), SiH(3), Li, and Na), were calculated at the
      MP2(Full)/aug-cc-pVTZ (aug-cc-pVTZ-PP on I) level of theory, without and with
      basis set superposition error (BSSE) corrections through the counterpoise (CP)
      method. The optimized complex geometries were analyzed through the Steiner
      Limbach relationship, which can be used to establish correlations between the F-X
      and X-C bond lengths. For all complexes, the correlations were shown to improve
      considerably when using optimized geometries including BSSE corrections. It was
      shown that further improvements can be achieved through the introduction of an
      extended four-parameter form of the Steiner-Limbach relationship which accounts
      for all differences between the valences associated with the two bonds involving
      the halogen in an A-X...B complex. The results indicate that chlorine as a
      halogen bond donor is affected by the basicity of the isocyanides and forms
      different types of halogen bonds as the F-Cl bond lengthens in parallel with the
      shortening of the distance between Cl and the isocyanide carbon. This is not
      observed for iodine and bromine as halogen-bond donors, which is illustrated by
      the low levels of correlation obtained when applying the standard and extended
      Steiner-Limbach relationships to the corresponding complexes.

PMID- 21888377
TI  - Utilization of glycosyltransferases for the synthesis of a densely packed
      hyperbranched polysaccharide brush coating as artificial glycocalyx.
AB  - Densely packed polysaccharide brushes consisting of alpha-D-glucose residues were
      grafted from modified silicon substrates. Potato phosphorylase was herein used to
      grow linear polysaccharide chains from silicon tethered maltoheptaose
      oligosaccharides using glucose-1-phosphate as donor substrate. The combined use
      of potato phosphorylase and Deinococcusgeothermalis branching enzyme resulted in
      a hyperbranched brush coating as the latter one redistributes short
      oligosaccharides from the alpha(1-4)-linked position to the alpha (1-6)-linked
      position in the polysaccharide brush. The obtained grafting density of the
      brushes was estimated on 1.89 nm(-2) while the thickness was measured with
      ellipsometric techniques and determined to be between 12.2 and 20.2 nm.

PMID- 21888376
TI  - Synchrotron infrared microspectroscopy detecting the evolution of Huntington's
      disease neuropathology and suggesting unique correlates of dysfunction in white
      versus gray brain matter.
AB  - Huntington's disease (HD), caused by a mutation of the corresponding gene
      encoding the protein huntingtin (htt), is characterized by progressive
      deterioration of cognitive and motor functions, paralleled by extensive loss of
      striatal neurons. At the cellular level, pathogenesis involves an early and
      prolonged period of neuronal dysfunction followed by neuronal death.
      Understanding the molecular events driving these deleterious processes is
      critical to the successful development of therapies to slow down or halt the
      progression of the disease. Here, we examined biochemical processes in a HD ex
      vivo rat model, as well as in a HD model for cultured neurons using synchrotron
      assisted Fourier transform infrared microspectroscopy (S-FTIRM). The model, based
      on lentiviral-mediated delivery of a fragment of the HD gene, expresses a mutant
      htt fragment in one brain hemisphere and a wild-type htt fragment in the control
      hemisphere. S-FTIRM allowed for high spatial resolution and distinction between
      spectral features occurring in gray and white matter. We measured a higher
      content of beta-sheet protein in the striatal gray matter exposed to mutant htt
      as early as 4 weeks following the initiation of mutant htt exposure. In contrast,
      white matter tracts did not exhibit any changes in protein structure but
      surprisingly showed reduced content of unsaturated lipids and a significant
      increase in spectral features associated with phosphorylation. The former is
      reminiscent of changes consistent with a myelination deficiency, while the latter
      is characteristic of early pro-apoptotic events. These findings point to the
      utility of the label-free FTIRM method to follow mutant htt's beta-sheet-rich
      transformation in striatal neurons ex vivo, provide further evidence for mutant
      htt amyloidogenesis in vivo, and demonstrate novel chemical features indicative
      of white matter changes in HD. Parallel studies in cultured neurons expressing
      the same htt fragments showed similar changes.

PMID- 21888378
TI  - Bioplastics from feather quill.
AB  - Poultry feather quills have been extruded in a twin screw extruder with sodium
      sulfite treatment as a reducing agent. The effect of four different plasticizers
      (ethylene glycol, propylene glycol, glycerol, and diethyl tartrate) on the
      thermoplastic properties was then investigated. Conformational changes and
      plasticizer-protein interactions in the extruded resins were assessed by Fourier
      transform infrared spectroscopy (FTIR), while viscoelastic behavior of the quill
      keratin plasticized with different plasticizers was investigated by dynamic
      mechanical analysis (DMA). Differential scanning calorimetry (DSC) was used to
      determine the effect of different plasticizers on protein denaturation. Thermal
      degradation patterns of the extrudates were studied by thermogravimetric analysis
      (TGA). The effect of plasticizers on the mechanical properties of resins was also
      assessed by tensile strength measurements. Results indicated that ethylene glycol
      was able to interact more effectively with quill keratin at the molecular level,
      exhibiting only one sharp glass transition, better mechanical properties, and
      higher transparency compared to other plasticized resins. The two phases found in
      glycerol plasticized material were attributed to glycerol-rich and protein-rich
      zones. Propylene glycol and diethyl tartrate exhibited lower H-bonding
      interactions and showed wide transition regions in DMA profiles during heating,
      suggesting weak and heterogeneous interactions between quill keratin and these
      plasticizers.

PMID- 21888379
TI  - Sorting mechanisms and communication in phase-separating coupled monolayers.
AB  - A continuous model of two coupled monolayers constituting a fluid bilayer
      membrane is presented. The model is based on the minimization of a membrane free
      energy considering in both monolayer leaflets two different molecule types,
      undergoing lateral phase separation. Differences in the mechanical properties of
      the molecules, such as shape, stiffness, and length are accounted explicitly by
      the model. In the presented model, coupling between monolayers is realized via an
      energy-based model depending on the local distance between the two monolayers as
      well as the lengths of molecules constituting the local monolayer region. We
      numerically study different passive mechanisms for molecule sorting and
      correlation across the bilayer induced by first-order mechanical constraints.
      Here, we focus on three aspects: First, we find that stretching of the two
      monolayers in the normal direction yields a sorting of molecules according to
      their length. Furthermore, we show that the length of molecules can be used to
      synchronize phases across the bilayer membrane. Moreover, we find that generating
      curvature in one layer (induced by different curvature creating mechanisms) sorts
      molecules of the other layer according to their shape and stiffness. Many recent
      experimental data indicate the importance of specific lipid-protein interactions
      and the role of the bilayer thickness in membrane protein function and sorting.
      The presented model proposes different mechanisms leading to a colocalization of
      different components in different monolayers at the same place at the same time.

PMID- 21888380
TI  - Long-range nanometer-scale organization of semifluorinated alkane monolayers at
      the air/water interface.
AB  - We have determined the structure formed at the air-water interface by
      semifluorinated alkanes (C(8)F(17)C(m)H(2m+1) diblocks, F8Hm for short) for
      different lengths of the molecule (m = 14, 16, 18, 20) by using surface pressure
      versus area per molecule isotherms, Brewster angle microscopy (BAM), and grazing
      incidence x-ray experiments (GISAXS and GIXD). The behavior of the monolayers of
      diblocks under compression is mainly characterized by a phase transition from a
      low-density phase to a condensed phase. The nonzero surface pressure phase is
      crystalline and exhibits two hexagonal lattices at two different scales: a long
      range-order lattice of a few tens of nanometers lateral parameter and a molecular
      array of about 0.6 nm parameter. The extent of this organization is sufficiently
      large to impact larger scale behavior. Analysis of the various compressibilities
      evidences the presence of non organized molecules in the monolayer for all 2D
      pressures. At room temperature, the self-assembled structure appears generic for
      all the F8Hm investigated.

PMID- 21888381
TI  - Design, overexpression, and purification of polymerization-blocked yeast
      alphabeta-tubulin mutants.
AB  - Microtubule dynamics play essential roles in intracellular organization and cell
      division. They result from structural and biochemical properties of alphabeta
      tubulin heterodimers and how these polymerizing subunits interact with themselves
      and with regulatory proteins. A broad understanding of the underlying mechanisms
      has been established, but fundamental questions remain unresolved. The lack of
      routine access to recombinant alphabeta-tubulin represents an obstacle to deeper
      insight into alphabeta-tubulin structure, biochemistry, and recognition. Indeed,
      the widespread reliance on animal brain alphabeta-tubulin means that very few in
      vitro studies have taken advantage of powerful and ordinarily routine techniques
      like site-directed mutagenesis. Here we report new methods for purifying wild
      type or mutant yeast alphabeta-tubulin from inducibly overexpressing strains of
      Saccharomyces cerevisiae. Inducible overexpression is an improvement over
      existing approaches that rely on constitutive expression: it provides higher
      yields while also allowing otherwise lethal mutants to be purified. We also
      designed and purified polymerization-blocked alphabeta-tubulin mutants. These
      "blocked" forms of alphabeta-tubulin give a dominant lethal phenotype when
      expressed in cells; they cannot form microtubules in vitro and when present in
      mixtures inhibit the polymerization of wild-type alphabeta-tubulin. The effects
      of blocking mutations are very specific, because purified mutants exhibit normal
      hydrodynamic properties, bind GTP, and interact with a tubulin-binding domain.
      The ability to overexpress and purify wild-type alphabeta-tubulin, or mutants
      like the ones we report here, creates new opportunities for structural studies of
      alphabeta-tubulin and its complexes with regulatory proteins, and for biochemical
      and functional studies of microtubule dynamics and its regulation.

PMID- 21888382
TI  - Application of the nano-positioning system to the analysis of fluorescence
      resonance energy transfer networks.
AB  - Single-molecule fluorescence resonance energy transfer (sm-FRET) has been
      recently applied to distance and position estimation in macromolecular complexes.
      Here, we generalize the previously published Nano-Positioning System (NPS), a
      probabilistic method to analyze data obtained in such experiments, which accounts
      for effects of restricted rotational freedom of fluorescent dyes, as well as for
      limited knowledge of the exact dye positions due to attachment via flexible
      linkers. In particular we show that global data analysis of complete FRET
      networks is beneficial and that the measurement of FRET anisotropies in addition
      to FRET efficiencies can be used to determine accurately both position and
      orientation of the dyes. This measurement scheme improves localization accuracy
      substantially, and we can show that the improvement is a consequence of the more
      precise information about the transition dipole moment orientation of the dyes
      obtained by FRET anisotropy measurements. We discuss also rigid body docking of
      different macromolecules by means of NPS, which can be used to study the
      structure of macromolecular complexes. Finally, we combine our approach with
      common FRET analysis methods to determine the number of states of a
      macromolecule.

PMID- 21888383
TI  - Excited-state properties of heteroleptic iridium(III) complexes bearing aromatic
      hydrocarbons with extended cores.
AB  - The synthesis, complete structural characterization, electrochemistry, and
      excited-state dynamics of a series of four bis-heteroleptic iridium(III) charge
      transfer complexes composed of a single acac-functionalized and two ortho
      metalated 2-phenylpyridine ligands. The formed iodophenyl complex (2) was used as
      a metallosynthon to introduce extended-core ethynyltolyl (3), ethynylpyrene (4),
      and ethynylperylene (5) residues into these structures projecting from the acac
      ancillary ligand. Static and dynamic photoluminescence along with ultrafast and
      conventional transient absorption measurements in conjunction with cyclic
      voltammetry were employed to elucidate the nature of the intramolecular energy
      transfer processes occurring in the excited states of polychromophores 4 and 5
      and are directly compared with those of model complexes 2 and 3. Upon charge
      transfer excitation of these molecules, the long-lived triplet-state metal-to
      ligand charge-transfer ((3)MLCT)-based photoluminescence readily observed in 2
      and 3 (tau = 1 MUs) is nearly quantitatively quenched, resulting from production
      of the associated triplet intraligand ((3)IL) excited states in 4 and 5 through
      intramolecular triplet-triplet energy transfer. The respective formation of the
      extended-core (3)*pyrenyl and (3)*perylenyl-localized excited states in 4 and 5
      is confirmed by their ultrafast excited-state evolution, which ultimately
      generates features associated with these (3)IL excited states and their greatly
      extended excited-state lifetimes with respect to the parent complexes 2 and 3.

PMID- 21888384
TI  - Selective and sensitive ratiometric detection of Hg(II) ions using a simple amino
      acid based sensor.
AB  - Synthesis of a novel pyrene derivative sensor (Py-Met) based on amino acid and
      its fluorescent behavior for Hg(II) in water was investigated. Upon Hg(II)
      binding, the Py-Met-bearing sulfonamide group exhibited a considerable excimer
      emission at 480 nm along with a decrease of monomer emission at 383 nm. Py-Met
      allows a selective and sensitive ratiometric detection of Hg(II) without any
      interference from other metal ions.

PMID- 21888385
TI  - Total synthesis of oxazolomycin A.
AB  - The first total synthesis of oxazolomycin A, a structurally novel oxazole polyene
      gamma-lactam/beta-lactone antibiotic, is described. Key features include the
      stereocontrolled construction of the right-hand heterocyclic core by taking
      advantage of an In(III)-catalyzed Conia-ene type cyclization and the asymmetric
      synthesis of the left-hand segment starting with a Cinchona alkaloid-catalyzed
      cyclocondensation of an aldehyde with an acid chloride.

PMID- 21888386
TI  - Effects of cyclization on stability, structure, and activity of alpha-conotoxin
      RgIA at the alpha9alpha10 nicotinic acetylcholine receptor and GABA(B) receptor.
AB  - alpha-Conotoxin RgIA is of interest as a lead in the development of drugs for
      neuropathic pain. It modulates the alpha9alpha10 nicotinic acetylcholine receptor
      (nAChR) and the GABA(B) receptor, both of which are implicated in
      antinociception. However, because of its peptidic nature, RgIA is potentially
      susceptible to generic problems encountered by peptide-based drugs of poor oral
      bioavailability, short biological half-life, and low stability. Here, we improved
      the biopharmaceutical properties of RgIA by backbone cyclization using 3-7
      residue peptidic linkers. Cyclization with a six-residue linker does not perturb
      the overall structure of RgIA, improves selectivity for the GABA(B) receptor over
      the alpha9alpha10 nAChR, and improves stability in human serum. The results
      provide insights to further improve the therapeutic properties of RgIA and other
      conotoxins being considered as drug leads and confirm that cyclization is a
      readily applicable strategy to improve the stability of peptides with proximate N
      and C-termini.

PMID- 21888387
TI  - Nucleation of silica nanoparticles measured in situ during controlled
      supersaturation increase. Restructuring toward a monodisperse nonspherical shape.
AB  - The first stages of the nucleation and growth of silica nanoparticles are
      followed in situ using both SAXS and Raman spectroscopy. Coupling these two
      techniques allows the determination of the fractions of soluble and solid silica
      as a function of the reaction time. SAXS also enables demonstrating that major
      modifications of the structure occur after the initial precipitation period,
      inducing an increase of the precipitate density. These structural modifications
      have important implications in the initial nucleation growth stages, which have
      never been introduced either in classical models or in more recent kinetic
      nucleation theories. Such restructuration stages could contribute to explain the
      monodispersity of the obtained silica nanoparticles that is not predicted by
      classical models.

PMID- 21888388
TI  - Direct functionalization of nanodiamond particles using dopamine derivatives.
AB  - The article reports on the strong linking of dopamine derivatives as a simple and
      a versatile strategy for the surface functionalization of hydroxyl-terminated
      nanodiamond (ND-OH) particles. Azide- (ND-N(3)) or poly-N-isopropylacrylamide
      terminated (ND-PNIPAM) particles were obtained from ND-OH particles through the
      reaction with the corresponding dopamine derivatives. The azide-terminated ND
      particles were further derivatized with a fluorescent probe, alkynyl-pyrene, via
      copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition. The modified ND particles
      were characterized using transmission Fourier transform infrared (FTIR)
      spectroscopy, UV-vis spectroscopy, electrochemical measurements,
      thermogravimetric analysis (TGA), and particle size measurements. The surface
      loading of ND particles with dopamine was estimated from TGA and UV-vis
      spectroscopy and was found to be around 0.27 mmol g(-1). Because of its simple,
      gentle nature and versatility, the chemistry developed in this work can be used
      as an avenue for the preparation of functional nanodiamond particles for various
      applications.

PMID- 21888389
TI  - Formation of interpenetrating hierarchical titania structures by confined
      synthesis in inverse opal.
AB  - Hierarchical periodic titania nanostructures composed of a macroporous
      crystalline scaffold and mesoporous titania were prepared by confined synthesis.
      The strategy for the generation of these hierarchical structures involves
      preparation of inverse opal titania layers and subsequent filling of the
      interstitial macroporous voids with surfactant-containing titania precursors to
      obtain a mesostructured titania phase using the surfactant Pluronic P123. The
      formation of mesostructure in the confined space of the macroporous scaffold upon
      thermal treatment was investigated with in situ grazing incidence small-angle X
      ray scattering (GISAXS). The macroporous scaffold strongly influences the
      mesostructure assembly and leads to much larger structural parameters of the
      formed mesostructure, this effect becoming more pronounced with decreasing pore
      size of the macroporous host. Furthermore, the inverse opal scaffold acts as a
      stabilizing matrix, limiting the shrinkage of the mesopores upon heating. This
      effect is coupled with an enhanced crystallization of the mesophase, which is
      attributed to the crystalline walls of the macroporous host. Sorption
      measurements of the final hierarchical titania structure of 5 MUm thickness show
      that the porous system is fully accessible, has a high total surface area of 154
      m(2)/g, and has an average mesopore size of 6.1 nm, which is about 20% larger
      than the pore size of 5.1 nm for the reference mesoporous film obtained on a flat
      substrate. These hierarchical structures were implemented as anodes in dye
      sensitized solar cells (DSCs), showing a conversion efficiency of 4% under one
      sun illumination, whereas the calcined macroporous scaffold alone shows an
      efficiency of only 0.4%.

PMID- 21888390
TI  - N-(2-{3-[3,5-bis(trifluoromethyl)phenyl]ureido}ethyl)-glycyrrhetinamide (6b): a
      novel anticancer glycyrrhetinic acid derivative that targets the proteasome and
      displays anti-kinase activity.
AB  - 18-beta-Glycyrrhetinic acid (GA; 1) and many of its derivatives are cytotoxic in
      cancer cells. The current study aims to characterize the anticancer effects of 17
      novel 1 derivatives. On the basis of these studies, N-(2-{3-[3,5
      bis(trifluoromethyl)phenyl]ureido}ethyl)-glycyrrhetinamide (6b) appeared to be
      the most potent compound, with IC(50)in vitro growth inhibitory concentrations in
      single-digit micromolarity in a panel of 8 cancer cell lines. Compound 6b is
      cytostatic and displays similar efficiency in apoptosis-sensitive versus
      apoptosis-resistant cancer cell lines through, at least partly, the inhibition of
      the activity of a cluster of a dozen kinases that are implicated in cancer cell
      proliferation and in the control of the actin cytoskeleton organization. Compound
      6b also inhibits the activity of the 3 proteolytic units of the proteasome.
      Compound 6b thus represents an interesting hit from which future compounds could
      be derived to improve chemotherapeutic regimens that aim to combat cancers
      associated with poor prognoses.

PMID- 21888392
TI  - V2O5-anchored carbon nanotubes for enhanced electrochemical energy storage.
AB  - Functionalized multiwalled carbon nanotubes (CNTs) are coated with a 4-5 nm thin
      layer of V(2)O(5) by controlled hydrolysis of vanadium alkoxide. The resulting
      V(2)O(5)/CNT composite has been investigated for electrochemical activity with
      lithium ion, and the capacity value shows both faradaic and capacitive
      (nonfaradaic) contributions. At high rate (1 C), the capacitive behavior
      dominates the intercalation as 2/3 of the overall capacity value out of 2700 C/g
      is capacitive, while the remaining is due to Li-ion intercalation. These numbers
      are in agreement with the Trasatti plots and are corroborated by X-ray
      photoelectron spectroscopy (XPS) studies on the V(2)O(5)/CNTs electrode, which
      show 85% of vanadium in the +4 oxidation state after the discharge at 1 C rate.
      The cumulative high-capacity value is attributed to the unique property of the
      nano V(2)O(5)/CNTs composite, which provides a short diffusion path for Li(+)
      ions and an easy access to vanadium redox centers besides the high conductivity
      of CNTs. The composite architecture exhibits both high power density and high
      energy density, stressing the benefits of using carbon substrates to design high
      performance supercapacitor electrodes.

PMID- 21888393
TI  - Upright standing graphene formation on substrates.
AB  - We propose integrating graphene nanoribbons (GNRs) onto a substrate in an upright
      position whereby they are chemically bound to the substrate at the basal edge.
      Extensive ab initio calculations show that both nickel (Ni)- and diamond
      supported upright GNRs are feasible for synthesis and are mechanically robust.
      Moreover, the substrate-supported GNRs display electronic and magnetic properties
      nearly the same as those of free-standing GNRs. Due to the extremely small
      footprint of an upright GNR on a substrate, standing GNRs are ideal building
      blocks for synthesis of subnanometer electronic or spintronic devices.
      Theoretically, standing GNR-based microchips with field-effect transistor (FET)
      densities up to 10(13) per cm(2) are achievable.

PMID- 21888394
TI  - Effect of cigarette menthol content on mainstream smoke emissions.
AB  - The 2009 Family Smoking Prevention and Tobacco Control Act empowered the U.S.
      Food and Drug Administration to study "the impact of the use of menthol in
      cigarettes on the public health, including such use among children, African
      Americans, Hispanics and other racial and ethnic minorities," and develop
      recommendations. Current scientific evidence comparing human exposures between
      menthol and nonmenthol smokers shows mixed results. This is largely because of
      the many differences between commercial menthol and nonmenthol cigarettes other
      than their menthol content. We conducted an innovative study using two types of
      test cigarettes: a commercial nonmenthol brand that we mentholated at four
      different levels, and Camel Crush, a commercial cigarette containing a small
      capsule in the filter that releases menthol solution into the filter when
      crushed. Cigarettes were machine-smoked at each of the menthol levels
      investigated, and the total particulate matter (TPM) was collected on a quartz
      fiber filter pad and analyzed by gas chromatography/mass spectrometry for
      menthol, nicotine, tobacco-specific nitrosamines (TSNAs), polycyclic aromatic
      hydrocarbons (PAHs), cotinine, and quinoline. The mainstream smoke was also
      monitored continuously in real time on a puff-by-puff basis for seven gas-phase
      constituents (acetaldehyde, acetonitrile, acrylonitrile, benzene, 1,3-butadiene,
      isoprene, and 2,5-dimethylfuran), using a proton transfer reaction-mass
      spectrometer. Average yields (in micrograms/cigarette) for the analytes were
      determined. Menthol in the TPM samples increased linearly with applied menthol
      concentration, but the amounts of nicotine along with the target TSNAs, PAHs,
      cotinine, and quinoline in the cigarettes remained essentially unchanged.
      Similarly, yields of the targeted volatile organic compounds (VOCs) in whole
      smoke from the mentholated nonmenthol cigarettes that were measured in real-time
      were largely unaffected by their menthol levels. In the Camel Crush cigarettes,
      however, the VOC yields appeared to increase in the presence of menthol,
      especially in the gas phase. Although we succeeded in characterizing key
      mainstream smoke constituents in cigarettes that differ only in menthol content,
      further study is needed to definitively answer whether menthol affects exposure
      to selected cigarette constituents and thereby influences harm.

PMID- 21888395
TI  - Toward functional Ni-SOD biomimetics: achieving a structural/electronic
      correlation with redox dynamics.
AB  - We have prepared and characterized a Ni complex with an N(3)S(2) ligand set (1)
      that represents the first isolable synthetic model of the reduced form of the Ni
      SOD (SOD = superoxide dismutase) active site featuring all relevant donor
      functionality in the proper spatial distribution. As revealed by X-ray
      crystallography, the axial py-N donor of 1 does not bind Ni(II) in the solid
      state or in solution like SOD. Oxidation of 1 provides a disulfide-linked
      dinuclear species, [{Ni(N(3)S(2))}(2)] (2), which we have isolated and
      characterized. Moreover, the 1 -> 2 conversion is reversible, much like redox
      cycling in the enzyme.

PMID- 21888396
TI  - Growth of bilayer graphene on insulating substrates.
AB  - Here we demonstrate a general transfer-free method to directly grow large areas
      of uniform bilayer graphene on insulating substrates (SiO(2), h-BN, Si(3)N(4),
      and Al(2)O(3)) from solid carbon sources such as films of poly(2
      phenylpropyl)methysiloxane, poly(methyl methacrylate), polystyrene, and
      poly(acrylonitrile-co-butadiene-co-styrene), the latter leading to N-doped
      bilayer graphene due to its inherent nitrogen content. Alternatively, the carbon
      feeds can be prepared from a self-assembled monolayer of butyltriethoxysilane
      atop a SiO(2) layer. The carbon feedstocks were deposited on the insulating
      substrates and then caped with a layer of nickel. At 1000  degrees C, under low
      pressure and a reducing atmosphere, the carbon source was transformed into a
      bilayer graphene film on the insulating substrates. The Ni layer was removed by
      dissolution, affording the bilayer graphene directly on the insulator with no
      traces of polymer left from a transfer step. The bilayer nature of as-grown
      samples was demonstrated by I(G)/I(2D) Raman mapping, the statistics of the full
      width at half-maximum of the Raman 2D peak, the selected area electron
      diffraction patterns over a large area, and randomly imaged graphene edges by
      high-resolution transmission electron microscopy.

PMID- 21888397
TI  - On the construction, comparison, and variability of airsheds for interpreting
      semivolatile organic compounds in passively sampled air.
AB  - Air mass origin as determined by back trajectories often aids in explaining some
      of the short-term variability in the atmospheric concentrations of semivolatile
      organic contaminants. Airsheds, constructed by amalgamating large numbers of back
      trajectories, capture average air mass origins over longer time periods and thus
      have found use in interpreting air concentrations obtained by passive air
      samplers. To explore some of their key characteristics, airsheds for 54 locations
      on Earth were constructed and compared for roundness, seasonality, and
      interannual variability. To avoid the so-called "pole problem" and to simplify
      the calculation of roundness, a "geodesic grid" was used to bin the back
      trajectory end points. Departures from roundness were seen to occur at all
      latitudes and to correlate significantly with local slope but no strong
      relationship between latitude and roundness was revealed. Seasonality and
      interannual variability vary widely enough to imply that static models of
      transport are not sufficient to describe the proximity of an area to potential
      sources of contaminants. For interpreting an air measurement an airshed should be
      generated specifically for the deployment time of the sampler, especially when
      investigating long-term trends. Samples taken in a single season may not
      represent the average annual atmosphere, and samples taken in linear, as opposed
      to round, airsheds may not represent the average atmosphere in the area. Simple
      methods are proposed to ascertain the significance of an airshed or individual
      cell. It is recommended that when establishing potential contaminant source
      regions only end points with departure heights of less than ~700 m be considered.

PMID- 21888398
TI  - Facile construction of high-electrocatalytic bilayer counter electrode for
      efficient dye-sensitized solar cells.
AB  - To improve the mechanical rigidity of the electrocatalyst and assure a higher
      number density of catalytic sites of the counter electrode in dye-sensitized
      solar cells (DSCs), we have extended widely applied titanium tetrachloride
      treatment to construct a rough scaffolding underlayer for the platinized counter
      electrode. Field-emission scanning electron microscopy and atomic force
      microscopy images clearly depicted the platinum nanoparticles with a diameter of
      ca. 10 nm homogeneously distributed on the scaffolding underlayer of the bilayer
      counter electrode and thus led to a characteristically high surface roughness.
      The electocatalytic activity of this novel bilayer counter electrode was measured
      and compared with the corresponding properties of conventional sputtered Pt
      electrode. Interestingly, electrochemical impedance spectroscopy and cyclic
      voltammetry measurements further demonstrated the notably larger electrochemical
      active surface area and thereby higher electrocatalytic activity of the bilayer
      counter electrode. Consequently, under standard 1 sun illumination (100 mW cm(
      2), AM 1.5), device with this bilayer counter electrode achieved a considerably
      improved fill factor of 0.67 and overall energy conversion efficiency of 7.09%,
      which was apparently higher than that of 0.60 and 6.37% for sputterd Pt
      electrode. Therefore, this present method paves a facile and inexpensive way to
      prepare high-electrocatalytic bilayer counter electrode in DSCs.

PMID- 21888399
TI  - Directed organization of C70 kagome lattice by titanyl phthalocyanine monolayer
      template.
AB  - Controlled deposition of titanyl phthalocyanine (TiOPc) on Ag(111) produces a
      honeycomb monolayer phase consisting of TiOPc molecules with two distinctive tilt
      angles. This periodic arrangement of polar molecules is used to direct C(70)
      growth into low-density 3D films with novel C(70) kagome lattice arrangements.
      Structural models for the C(70) kagome lattice are determined from layer-by-layer
      scanning tunneling microscopy images and related to the dipolar TiOPc template
      and C(70)'s anisotropic polarizability. Molecular templates with designed
      electrostatic features offer a practical method to control 3D film organization
      on the nanoscale by harnessing anisotropic molecular interactions at the growth
      interface.

PMID- 21888400
TI  - Direct measurement of the dynamics of excess electron transfer through
      consecutive thymine sequence in DNA.
AB  - Charge transfer in DNA is an essential process in biological systems because of
      its close relation to DNA damage and repair. DNA is also an important material
      used in nanotechnology for wiring and constructing various nanomaterials.
      Although hole transfer in DNA has been investigated by various researchers and
      the dynamic properties of this process have been well established, the dynamics
      of a negative charge, that is, excess electron, in DNA have not been revealed
      until now. In the present paper, we directly measured the rate of excess electron
      transfer (EET) through a consecutive thymine (T) sequence in nicked-dumbbell DNAs
      conjugated with a tetrathiophene derivative (4T) as an electron donor and
      diphenylacetylene (DPA) as an electron acceptor at both ends. The selective
      excitation of 4T by a femtosecond laser pulse caused the excess electron
      injection into DNA, and led to EET in DNA by a consecutive T-hopping mechanism,
      which eventually formed the DPA radical anion (DPA(*-)). The rate constant for
      the process of EET through consecutive T was determined to be (4.4 +/- 0.3) *
      10(10) s(-1) from an analysis of the kinetic traces of the DeltaO.D. during the
      laser flash photolysis. It should be emphasized that the EET rate constant for T
      hopping is faster than the rate constants for oxidative hole transfers in DNA
      (10(4) to 10(10) s(-1) for A- and G-hopping).

PMID- 21888401
TI  - Heterobimetallic complexes containing Ca-Fe or Yb-Fe bonds: synthesis and
      molecular and electronic structures of [M{CpFe(CO)2}2(THF)3]2 (M = Ca or Yb).
AB  - Reaction of calcium or ytterbium amalgam with [CpFe(CO)(2)](2) (Fp(2)) gave the
      isostructural heavy alkaline earth or divalent rare earth compounds
      [MFp(2)(THF)(3)](2) (M = Ca or Yb) containing two direct Ca-Fe (3.0185(6) A) or
      Yb-Fe (2.9892(4) A) bonds. Density functional theory supports experiment in
      finding shorter Yb-Fe than Ca-Fe distances, and Ziegler-Rauk, molecular orbital,
      and atoms-in-molecules analyses find the M-Fe bonding to be predominantly
      electrostatic in nature. The Yb-Fe interaction energy and bond critical point
      electron density are slightly larger than for Ca-Fe, in agreement with the
      shorter M-Fe bond in the former. The corresponding reaction for magnesium gave
      MgFp(2)(THF)(4) with two O-bound Fp moieties and no Mg-Fe bond.

PMID- 21888402
TI  - Non-Nernstian two-electron transfer photocatalysis at metalloporphyrin-TiO2
      interfaces.
AB  - A long-standing question in the photochemical sciences concerns how to integrate
      single-electron transfers to catalytic multielectron transfer reactions that
      produce useful chemical fuels. Here we provide a strategy for the two-electron
      formation of C-C bonds with molecular catalysts anchored to semiconductor
      nanocrystallites. The blue portion of the solar spectrum provides band gap
      excitation of the semiconductor while longer wavelengths of light initiate
      homolytic cleavage of metal-carbon bonds that, after interfacial charge transfer,
      restore the catalyst. The semiconductor utilized was the anatase polymorph of
      TiO(2) present as a nanocrystalline, mesoporous thin film. The catalyst was
      cobalt meso-5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin chloride, Co(TCPP)Cl.
      For this catalyst and iron protoporphyrin IX chloride, Fe(PPIX)Cl, two distinct
      and sequential metal-based M(III/II) and M(II/I) reductions were observed under
      band gap illumination. Spectroelectrochemical characterization indicated that
      both reductions were non-Nernstian, behavior attributed to an environmentally
      dependent potential drop across the molecule-semiconductor interface. Reaction of
      Co(I)(TCPP)/TiO(2) with organobromides (RBr = 1-Br-hexane or benzyl bromide)
      resulted in the formation of Co(III)-R(TCPP)/TiO(2). Visible light excitation
      induced homolytic cleavage of the Co-C bond and the formation of C-C-bonded
      products. The reactions were catalytic when band gap excitation or an
      electrochemical bias provided TiO(2) electrons to the oxidized catalyst.
      Sustained photocurrents were quantified in photoelectrosynthetic solar cells
      under forward bias.

PMID- 21888403
TI  - Light-induced spin change by photodissociable external ligands: a new principle
      for magnetic switching of molecules.
AB  - Magnetic bistability in spin-crossover materials generally is a collective
      phenomenon that arises from the cooperative interaction of a large number of
      microscopic magnetic moments within the crystal lattice in the solid state. We
      now report on individual molecules in homogeneous solution that are switched
      between the diamagnetic and paramagnetic states at room temperature by light
      driven coordination-induced spin-state switching (LD-CISSS). Switching of the
      coordination number (and concurrently of the spin state) was achieved by using Ni
      porphyrin as a square-planar platform and azopyridines as photodissociable axial
      ligands. The square-planar Ni-porphyrin is diamagnetic (low-spin, S = 0), and all
      complexes with axial ligands are paramagnetic (high-spin, S = 1). Association
      constants were determined for all conceivable 1:1 and 1:2 porphyrin/azopyridine
      complexes. The binding constants of the trans azopyridines are larger than those
      of the corresponding cis isomers. Thus, upon irradiation with UV light (365 nm,
      trans -> cis) and visible light (455 nm, cis -> trans), switching of the magnetic
      properties was achieved. Upon substitution of the azopyridines at the 4- and 4'
      positions with larger substituents, the difference in trans and cis association
      constants, and thus the switching efficiency, was increased. A photoinduced,
      reversible switching between 20 and 68% paramagnetic Ni species in solution was
      achieved with isopropyl substituents at room temperature.

PMID- 21888404
TI  - Plasma profiling reveals human fibulin-1 as candidate marker for renal
      impairment.
AB  - There is a need for reliable and sensitive biomarkers for renal impairments to
      detect early signs of kidney toxicity and to monitor progression of disease.
      Here, antibody suspension bead arrays were applied to profile plasma samples from
      patients with four types of kidney disorders: glomerulonephritis, diabetic
      nephropathy, obstructive uropathy, and analgesic abuse. In total, 200 clinical
      renal-associated cases and control plasma samples from different cohorts were
      profiled. Parallel plasma protein profiles were obtained using biotinylated and
      nonfractionated samples and a selected set of 94 proteins targeted by 129 antigen
      purified polyclonal antibodies. Out of the analyzed target proteins, human
      fibulin-1 was detected at significantly higher levels in the glomerulonephritis
      patient group compared to the controls and with elevated levels in patient
      samples for all other renal disorders investigated. Two polyclonal antibodies and
      one monoclonal antibody directed toward separate, nonoverlapping epitopes showed
      the same trend in the discovery cohorts. A technical verification using Western
      blot analysis of selected patient plasma confirmed the trends toward higher
      abundance of the target protein in disease samples. Furthermore, a verification
      study was carried out in the context of glomerulonephritis using an independent
      case and control cohort, and this confirmed the results from the discovery
      cohort, suggesting that plasma levels of fibulin-1 could serve as a potential
      indicator to monitor kidney malfunction or kidney damage.

PMID- 21888405
TI  - Blackberry extract attenuates oxidative stress through up-regulation of Nrf2
      dependent antioxidant enzymes in carbon tetrachloride-treated rats.
AB  - The aim of this study was to investigate the protective ability of blackberry
      extract (BE) against oxidative stress in carbon tetrachloride (CCl(4))-treated
      rats. The results showed that treatment with BE attenuated lipid peroxidation
      that was increased by CCl(4) and also markedly recovered the activity of
      antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT),
      glutathione peroxidase (GPx), and glutathione reductase (GR), that were decreased
      by CCl(4). BE also elevated the protein expression levels of NF-E2-related factor
      2 (Nrf2), CuZnSOD, MnSOD, GPx-1/2, and heme oxygenase-1 (HO-1), but not that of
      catalase. Furthermore, the administration of BE significantly attenuated the
      levels of serum aspartate aminotransferase (AST) and alanine aminotransferase
      (ALT) that were increased by CCl(4). Therefore, the present study suggests that
      BE possesses significant protective effects against in vivo oxidative stress.

PMID- 21888406
TI  - Hydrogen-bonded proton transfer in the protonated guanine-cytosine (GC+H)+ base
      pair.
AB  - The single proton transfer at the different sites of the Watson-Crick (WC)
      guanine-cytosine (GC) DNA base pair are studied here using density functional
      methods. The conventional protonated structures, transition state (TS) and proton
      transferred product (PT) structures of every relevant species are optimized. Each
      transition state and proton-transferred product structure has been compared with
      the corresponding conventional protonated structure to demonstrate the process of
      proton transfer and the change of geometrical structures. The relative energies
      of the protonated tautomers and the proton-transfer energy profiles in gas and
      solvent are analyzed. The proton-transferred product structure G(+H(+))
      H(+)C(N3)(-H(+))(PT) has the lowest relative energy for which only two hydrogen
      bonds exist. Almost all 14 isomers of the protonated GC base pair involve
      hydrogen-bonded proton transfer following the three pathways, with the exception
      of structure G-H(+)C(O2). When the positive charge is primarily "located" on the
      guanine moiety (H(+)G-C, G-H(+)C(C4), and G-H(+)C(C6)), the H(1) proton transfers
      from the N(1) site of guanine to the N(3) site of cytosine. The structures G
      H(+)C(C5) and G-H(+)C(C4) involve H(4a) proton transfer from the N(4) of cytosine
      to the O(6) site of guanine. H(2a) proton transfer from the N(2) site of guanine
      to the O(2) site of cytosine is found only for the structure G-H(+)C(C4). The
      structures to which a proton is added on the six-centered sites adjoining the
      hydrogen bonds are more prone to proton transfer in the gas phase, whereas a
      proton added on the minor groove and the sites adjoining the hydrogen bonds is
      favorable to the proton transfer in energy in the aqueous phase.

PMID- 21888407
TI  - The photothermal stability of PbS quantum dot solids.
AB  - We combine optical absorption spectroscopy, ex situ transmission electron
      microscopy (TEM) imaging, and variable-temperature measurements to study the
      effect of ultraviolet (UV) light and heat treatments on ethanedithiol-treated PbS
      quantum dot (QD) films as a function of ambient atmosphere, temperature, and QD
      size. Film aging occurs mainly by oxidation or ripening and sintering depending
      on QD size and the presence of oxygen. We can stop QD oxidation and greatly
      suppress ripening by infilling the films with amorphous Al(2)O(3) using room
      temperature atomic layer deposition (ALD).

PMID- 21888408
TI  - Patterning of plasmonic nanoparticles into multiplexed one-dimensional arrays
      based on spatially modulated electrostatic potential.
AB  - We report a new strategy to pattern plasmonic nanoparticles into multiplexed one
      dimensional arrays based on the spatially modulated electrostatic potential. The
      32 nm Au nanoparticles can be simultaneously deposited on one chip with tunable
      interparticle distance by solely adjusting the width of the grooves. Furthermore,
      32 and 13 nm Au nanoparticles can be selectively deposited in grooves of
      different widths on one chip. As a result, the surface plasmon absorption bands
      on the chip can be tuned depending on the interparticle distance or the particle
      size of multiplex 1D arrays, which could enhance the Raman scattering cross
      section of the adsorbed molecules and result in multiplex surface-enhanced Raman
      scattering (SERS) response on the chip. This strategy provides a general method
      to fabricate 1D multiplex arrays with different particle sizes and interparticle
      distances on one chip.

PMID- 21888409
TI  - Facile synthesis of Pd-Pt alloy nanocages and their enhanced performance for
      preferential oxidation of CO in excess hydrogen.
AB  - This article describes a new method for the facile synthesis of Pd-Pt alloy
      nanocages with hollow interiors and porous walls by using Pd nanocubes as
      sacrificial templates. Differing from our previous work (Zhang, H.; Jin, M. S.;
      Wang, J. G.; Li, W. Y.; Camargo, P. H. C.; Kim, M. J.; Yang, D. R.; Xie, Z. X.;
      Xia, Y. Synthesis of Pd-Pt Bimetallic Nanocrystals with a Concave Structure
      through a Bromide-Induced Galvanic Replacement Reaction. J. Am. Chem. Soc.2011,
      133, 6078-6079), we complemented the galvanic replacement (between Pd nanocubes
      and PtCl(4)(2-)) with a coreduction process (for PdCl(4)(2-) from the galvanic
      reaction and PtCl(4)(2-) from the feeding) to generate Pd-Pt alloy nanocages in
      one step. We found that the rate of galvanic replacement (as determined by the
      concentrations of Br(-) and PtCl(4)(2-) and temperature) and the rates of
      coreduction (as determined by the type of reductant and temperature) played
      important roles in controlling the morphology of resultant Pd-Pt alloy nanocages.
      The Pd-Pt nanocages exhibited both enhanced activity and selectivity for the
      preferential oxidation (PROX) of CO in excess hydrogen than those of Pd nanocubes
      and the commercial Pt/C thanks to the alloy composition and hollow structure. In
      addition, as the sizes of the Pd-Pt nanocages decreased, they exhibited higher CO
      conversion rates and lower maximum conversion temperatures due to the increase in
      specific surface area.

PMID- 21888410
TI  - Measuring agglomerate size distribution and dependence of localized surface
      plasmon resonance absorbance on gold nanoparticle agglomerate size using
      analytical ultracentrifugation.
AB  - Agglomeration of nanoparticles during measurements in relevant biological and
      environmental media is a frequent problem in nanomaterial property
      characterization. The primary problem is typically that any changes to the size
      distribution can dramatically affect the potential nanotoxicity or other size
      determined properties, such as the absorbance signal in a biosensor measurement.
      Herein we demonstrate analytical ultracentrifugation (AUC) as a powerful method
      for measuring two critical characteristics of nanoparticle (NP) agglomerates in
      situ in biological media: the NP agglomerate size distribution, and the localized
      surface plasmon resonance (LSPR) absorbance spectrum of precise sizes of gold NP
      agglomerates. To characterize the size distribution, we present a theoretical
      framework for calculating the hydrodynamic diameter distribution of NP
      agglomerates from their sedimentation coefficient distribution. We measure
      sedimentation rates for monomers, dimers, and trimers, as well as for larger
      agglomerates with up to 600 NPs. The AUC size distributions were found generally
      to be broader than the size distributions estimated from dynamic light scattering
      and diffusion-limited colloidal aggregation theory, an alternative bulk
      measurement method that relies on several assumptions. In addition, the measured
      sedimentation coefficients can be used in nanotoxicity studies to predict how
      quickly the agglomerates sediment out of solution under normal gravitational
      forces, such as in the environment. We also calculate the absorbance spectra for
      monomer, dimer, trimer, and larger gold NP agglomerates up to 600 NPs, to enable
      a better understanding of LSPR biosensors. Finally, we validate a new method that
      uses these spectra to deconvolute the net absorbance spectrum of an unknown bulk
      sample and approximate the proportions of monomers, dimers, and trimers in a
      polydisperse sample of small agglomerates, so that every sample does not need to
      be measured by AUC. These results demonstrate the potential utility of AUC to
      characterize NP agglomeration and sedimentation for nanotoxicity and biosensor
      studies, as well as to characterize NP agglomerate size and absorbance to improve
      LSPR and surface-enhanced Raman spectroscopy based biosensors.

PMID- 21888411
TI  - Molecular-scale size tuning of covalently bound assembly of C60 molecules.
AB  - The creation of a molecular-scale covalently bound assembly of fullerene C(60)
      molecules has been precisely controlled in ultrathin multilayer films of C(60)
      molecules. When a negative sample bias voltage is applied to a tunneling junction
      between the C(60) film and the tip of a scanning tunneling microscope (STM), a
      C(60) molecule beneath the tip covalently bonds to an adjacent molecule in the
      underneath layer. We show that such a chemical reaction is not necessarily
      limited to the top and second layers of the C(60) film and that the resulting
      C(60) oligomer can be tuned to form a dimer, trimer, tetramer, or pentamer; the
      number of interconnected C(60) molecules increases one by one upon increasing the
      magnitude of the local electric field under the STM tip. The created oligomers
      are linear chains of C(60) molecules starting from the top layer and aligned
      toward the interface layer in the multilayer C(60) films. We consider that the
      electrostatic negative ionization of C(60) molecules and its spatial distribution
      in the multilayer C(60) film are critical factors in achieving size-tunable
      oligomerization.

PMID- 21888412
TI  - Crystalline Gibbs monolayers of DNA-capped nanoparticles at the air-liquid
      interface.
AB  - Using grazing-incidence small-angle X-ray scattering in a special configuration
      (parallel SAXS, or parSAXS), we mapped the crystallization of DNA-capped
      nanoparticles across a sessile droplet, revealing the formation of crystalline
      Gibbs monolayers of DNA-capped nanoparticles at the air-liquid interface. We
      showed that the spatial crystallization can be regulated by adjusting both ionic
      strength and DNA sequence length and that a modified form of the Daoud-Cotton
      model could describe and predict the resulting changes in interparticle spacing.
      Gibbs monolayers at the air-liquid interface provide an ideal platform for the
      formation and study of equilibrium nanostructures and may afford exciting routes
      toward the design of programmable 2D plasmonic materials and metamaterials.

PMID- 21888413
TI  - Tailoring surface properties of paper using nanosized precipitated calcium
      carbonate particles.
AB  - Pigment particles used in paper coatings are typically of micrometer size and
      consequently the thickness of the coatings is, even at its lowest, in micrometer
      scale. Progress in nanotechnology has given way to the development of nanosized
      materials to be used in coatings, yet their exploitation has not been studied to
      a great extent. This study examines utilization of nanosized precipitated calcium
      carbonate (nanoPCC) particles in nanoscale thin coating layers. In contrast to
      commonly used coatings, a thin nanoparticle-based coating was targeted to change
      the substrate surface characteristics via controlled surface structure rather
      than via high coat weight. A novel approach for stabilizing and modifying the
      nanoPCC particles with pectin and alkenyl succinic anhydride (ASA) was utilized
      and a nanoparticle coating with uniform particle distribution was created. The
      coating applied on paper substrate was hydrophobic, having a water contact angle
      of 125 degrees . Particle surface modification provided dispersion stability,
      enabling control of the coating layer structure. The introduced concept provides
      a new approach to paper coatings utilizing controlled deposition of nanoparticles
      with extremely low coat weight, yet having high impact on substrate surface
      properties. Additionally, as paper is an environmentally sound product, the
      approach to form a controllable nanostructure on a green substrate has potential
      in applications outside the traditional paper products.

PMID- 21888414
TI  - Microplates with adaptive surfaces.
AB  - Here we present a new and versatile method for the modification of the well
      surfaces of polystyrene microtiter plates (microplates) with poly(N
      phenylethylene diamine methacrylamide), (poly-NPEDMA). The chemical grafting of
      poly-NPEDMA to the surface of microplates resulted in the formation of thin
      layers of a polyaniline derivative bearing pendant methacrylamide double bonds.
      These were used as the attachment point for various functional polymers through
      photochemical grafting of various, for example, acrylate and methacrylate,
      polymers with different functionalities. In a model experiment, we have modified
      poly-NPEDMA-coated microplates with a small library of polymers containing
      different functional groups using a two-step approach. In the first step, double
      bonds were activated by UV irradiation in the presence of N,N
      diethyldithiocarbamic acid benzyl ester (iniferter). This enabled grafting of the
      polymer library in the second step by UV irradiation of solutions of the
      corresponding monomers in the microplate wells. The uniformity of coatings was
      confirmed spectrophotometrically, by microscopic imaging and by contact angle
      measurements (CA). The feasibility of the current technology has been shown by
      the generation of a small library of polymers grafted to the microplate well
      surfaces and screening of their affinity to small molecules, such as atrazine, a
      trio of organic dyes, and a model protein, bovine serum albumin (BSA). The
      stability of the polymers, reproducibility of measurement, ease of preparation,
      and cost-effectiveness make this approach suitable for applications in high
      throughput screening in the area of materials research.

PMID- 21888416
TI  - New insights into selective heterogeneous nucleation of metal nanoparticles on
      oxides by microwave-assisted reduction: rapid synthesis of high-activity
      supported catalysts.
AB  - Microwave-based methods are widely employed to synthesize metal nanoparticles on
      various substrates. However, the detailed mechanism of formation of such hybrids
      has not been addressed. In this paper, we describe the thermodynamic and kinetic
      aspects of reduction of metal salts by ethylene glycol under microwave heating
      conditions. On the basis of this analysis, we identify the temperatures above
      which the reduction of the metal salt is thermodynamically favorable and
      temperatures above which the rates of homogeneous nucleation of the metal and the
      heterogeneous nucleation of the metal on supports are favored. We delineate
      different conditions which favor the heterogeneous nucleation of the metal on the
      supports over homogeneous nucleation in the solvent medium based on the
      dielectric loss parameters of the solvent and the support and the metal/solvent
      and metal/support interfacial energies. Contrary to current understanding, we
      show that metal particles can be selectively formed on the substrate even under
      situations where the temperature of the substrate is lower than that of the
      surrounding medium. The catalytic activity of the Pt/CeO(2) and Pt/TiO(2) hybrids
      synthesized by this method for H(2) combustion reaction shows that complete
      conversion is achieved at temperatures as low as 100  degrees C with Pt-CeO(2)
      catalyst and at 50  degrees C with Pt-TiO(2) catalyst. Our method thus opens up
      possibilities for rational synthesis of high-activity supported catalysts using a
      fast microwave-based reduction method.

PMID- 21888415
TI  - Detection of lysozyme magnetic relaxation switches based on aptamer
      functionalized superparamagnetic nanoparticles.
AB  - Magnetic relaxation switch (MRSw) detection is based on aggregate formation or
      dissociation when magnetic nanoparticles (MNPs) bind to target molecules. In the
      aggregated state, the dephasing rate of nearby proton spins is higher than in the
      dispersed state, resulting in a decrease in the spin-spin relaxation time, T(2).
      In this work, an MRSw-based nanosensor for lysozyme (Lys) protein detection was
      achieved using iron oxide nanoparticles conjugated with either Lys aptamer or
      linker DNA, which can hybridize with the extended part of the aptamer to form
      clusters. Upon the addition of Lys, the aptamers bind with their targets, leading
      to disassembly of clusters and an increase in T(2). A detection limit in the
      nanomolar range was achieved for Lys detection in both buffer and human serum.
      The determination of Lys level in different types of cancer cell lysates was also
      performed to demonstrate detection in real clinical samples.

PMID- 21888417
TI  - Strong and tough cellulose nanopaper with high specific surface area and
      porosity.
AB  - In order to better understand nanostructured fiber networks, effects from high
      specific surface area of nanofibers are important to explore. For cellulose
      networks, this has so far only been achieved in nonfibrous regenerated cellulose
      aerogels. Here, nanofibrillated cellulose (NFC) is used to prepare high surface
      area nanopaper structures, and the mechanical properties are measured in tensile
      tests. The water in NFC hydrogels is exchanged to liquid CO2, supercritical CO2,
      and tert-butanol, followed by evaporation, supercritical drying, and sublimation,
      respectively. The porosity range is 40-86%. The nanofiber network structure in
      nanopaper is characterized by FE-SEM and nitrogen adsorption, and specific
      surface area is determined. High-porosity TEMPO-oxidized NFC nanopaper (56%
      porosity) prepared by critical point drying has a specific surface area as high
      as 482 m(2) g(-1). The mechanical properties of this nanopaper structure are
      better than for many thermoplastics, but at a significantly lower density of only
      640 kg m(-3). The modulus is 1.4 GPa, tensile strength 84 MPa, and strain-to
      failure 17%. Compared with water-dried nanopaper, the material is softer with
      substantiallly different deformation behavior.

PMID- 21888418
TI  - Electrospun polyurethane fibers for absorption of volatile organic compounds from
      air.
AB  - Electrospun polyurethane fibers for removal of volatile organic compounds (VOC)
      from air with rapid VOC absorption and desorption have been developed.
      Polyurethanes based on 4,4-methylenebis(phenylisocyanate) (MDI) and aliphatic
      isophorone diisocyanate as the hard segments and butanediol and tetramethylene
      glycol as the soft segments were electrospun from their solutions in N,N
      dimethylformamide to form micrometer-sized fibers. Although activated carbon
      possessed a many-fold higher surface area than the polyurethane fiber meshes, the
      sorption capacity of the polyurethane fibers was found to be similar to that of
      activated carbon specifically designed for vapor adsorption. Furthermore, in
      contrast to VOC sorption on activated carbon, where complete regeneration of the
      adsorbent was not possible, the polyurethane fibers demonstrated a completely
      reversible absorption and desorption, with desorption obtained by a simple
      purging with nitrogen at room temperature. The fibers possessed a high affinity
      toward toluene and chloroform, but aliphatic hexane lacked the necessary strong
      attractive interactions with the polyurethane chains and therefore was less
      strongly absorbed. The selectivity of the polyurethane fibers toward different
      vapors, along with the ease of regeneration, makes them attractive materials for
      VOC filtration.

PMID- 21888419
TI  - Diketopyrrolopyrrole-based pi-bridged donor-acceptor polymer for photovoltaic
      applications.
AB  - We report the synthesis, properties, and photovoltaic applications of a new
      conjugated copolymer (C12DPP-pi-BT) containing a donor group (bithiophene) and an
      acceptor group (2,5-didodecylpyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione), bridged by
      a phenyl group. Using cyclic voltammetry, we found the energy levels of C12DPP-pi
      BT are intermediate to common electron donor and acceptor photovoltaic materials,
      poly (3-hexylthiophene-2,5-diyl) (P3HT) and [6,6]-phenyl-C61-butyric acid methyl
      ester (PCBM), respectively. Whereas P3HT and PCBM are exclusively electron
      donating or accepting, we predict C12DPP-pi-BT may uniquely serve as either an
      electron donor or an acceptor when paired with PCBM or P3HT forming junctions
      with large built-in potentials. We confirmed the ambipolar nature of C12DPP-pi-BT
      in space charge limited current measurements and in C12DPP-pi-BT:PCBM and C12DPP
      pi-BT:P3HT bulk heterojunction solar cells, achieving power conversion
      efficiencies of 1.67% and 0.84%, respectively, under illumination of AM 1.5G (100
      mW/cm(2)). Adding diiodooctane to C12DPP-pi-BT:PCBM improved donor-acceptor inter
      mixing and film uniformity, and therefore enhanced charge separation and overall
      device efficiency. Using higher-molecular-weight polymer C12DPP-pi-BT in both
      C12DPP-pi-BT:PCBM and C12DPP-pi-BT:P3HT devices improved charge transport and
      hence the performance of the solar cells. In addition, we compared the structural
      and electronic properties of C12DPP-pi-BT:PCBM and C12DPP-pi-BT:P3HT blends,
      representing the materials classes of polymer:fullerene and polymer:polymer
      blends. In C12DPP-pi-BT:PCBM blends, higher short circuit currents were obtained,
      consistent with faster charge transfer and balanced electron and hole transport,
      but lower open circuit voltages may be reduced by trap-assisted recombination and
      interfacial recombination losses. In contrast, C12DPP-pi-BT:P3HT blends exhibit
      higher open circuit voltage, but short circuit currents were limited by charge
      transfer between the polymers. In conclusion, C12DPP-pi-BT is a promising
      material with intrinsic ambipolar characteristics for organic photovoltaics and
      may operate as either a donor or acceptor in the design of bulk heterojunction
      solar cells.

PMID- 21888420
TI  - Storable arylpalladium(II) reagents for alkene labeling in aqueous media.
AB  - We show that arylpalladium(II) reagents linked to biotin and indocyanine dye
      residues can be prepared by decarboxylative palladation of appropriately
      substituted electron-rich benzoic acid derivatives. When prepared under the
      conditions described, these organometallic intermediates are tolerant of air and
      water, can be stored for several months in solution in dimethyl sulfoxide, and
      permit biotin- and indocyanine dye-labeling of functionally complex olefinic
      substrates in water by Heck-type coupling reactions.

PMID- 21888421
TI  - Asymmetric synthesis of ageliferin.
AB  - We describe herein an asymmetric synthesis of ageliferin. A Mn(III)-mediated
      oxidative radical cyclization reaction was used as the key step to construct the
      core skeleton of this pyrrole-imidazole dimer. This approach resembles the
      biogenic [4 + 2] dimerization in an intramolecular fashion.

PMID- 21888422
TI  - Chemoselective samarium-mediated benzoyloxysulfone eliminations.
AB  - An investigation of the substrate dependence on the rate of samarium-mediated
      reductive elimination of beta-acyloxysulfones has provided insights into the
      mechanism of this transformation and allowed for the development of a
      chemoselective elimination process.

PMID- 21888423
TI  - Toward the early evaluation of therapeutic effects: an electrochemical platform
      for ultrasensitive detection of apoptotic cells.
AB  - The ability for early evaluation of therapeutic effects is a significant
      challenge in leukemia research. To address this challenge, we developed a novel
      electrochemical platform for ultrasensitive and selective detection of apoptotic
      cells in response to therapy. In order to construct the platform, a novel three
      dimensional (3-D) architecture was initially fabricated after combining nitrogen
      doped carbon nanotubes and gold nanoparticles via a layer-by-layer method. The
      formed architecture provided an effective matrix for annexin V with high
      stability and bioactivity to enhance sensitivity. On the basis of the specific
      recognition between annexin V and phosphatidylserine on the apoptotic cell
      membrane, the annexin V/3-D architecture interface showed a predominant
      capability for apoptotic cell capture. Moreover, a lectin-based nanoprobe was
      designed by noncovalent assembly of concanavalin A on CdTe quantum dots (QDs)
      labeled silica nanospheres with poly(allylamine hydrochloride) as a linker. This
      nanoprobe incorporated both the specific carbohydrate recognition and the
      multilabeled QDs-based signal amplification. By coupling with the QDs-based
      nanoprobe and electrochemical stripping analysis, the proposed sandwich-type
      cytosensor showed an excellent analytical performance for the ultrasensitive
      detection of apoptotic cells (as low as 48 cells), revealing great potential
      toward the early evaluation of therapeutic effects.

PMID- 21888424
TI  - Microscale phosphoproteome analysis of 10,000 cells from human cancer cell lines.
AB  - We developed a miniaturized LC-MS system with a high-recovery phosphopeptide
      enrichment protocol that allows phosphoproteome analysis of 10(4) cells. In the
      enrichment protocol, the key step is to add sodium deoxycholate and sodium
      lauroyl sarcosinate to the buffer solution for protein extraction and digestion
      and to omit any subsequent desalt/desurfactant step before phosphopeptide
      enrichment. The phosphopeptides enriched by hydroxy acid-modified metal oxide
      chromatography (HAMMOC) are directly injected onto a miniaturized LC column using
      a nitrogen-pressure-driven cell, instead of switching valve-type injectors. The
      miniaturized analytical column of 25 MUm diameter provided a 3.6-fold improvement
      in sensitivity over the conventional 100 MUm diameter column. Overall, our
      analytical system provided approximately 80-fold improvement on average in the LC
      MS response, and we identified 1011 unique phosphorylated sites based on 995
      unique phosphopeptides from a single analysis of 10(4) HeLa cells (approximately
      1 MUg of proteins). This is the most sensitive phosphoproteomics system that has
      so far been reported for proteome-wide analysis of in vivo phosphorylation in
      mammalian cells.

PMID- 21888426
TI  - Direct growth of bilayer graphene on SiO2 substrates by carbon diffusion through
      nickel.
AB  - Here we report a transfer-free method of synthesizing bilayer graphene directly
      on SiO(2) substrates by carbon diffusion through a layer of nickel. The 400 nm
      nickel layer was deposited on the top of SiO(2) substrates and used as the
      catalyst. Spin-coated polymer films such as poly(methyl methacrylate), high
      impact polystyrene or acrylonitrile-butadiene-styrene, or gas-phase methane were
      used as carbon sources. During the annealing process at 1000  degrees C, the
      carbon sources on the top of the nickel decomposed and diffused into the nickel
      layer. When cooled to room temperature, bilayer graphene was formed between the
      nickel layer and the SiO(2) substrates. The nickel films were removed by
      etchants, and bilayer graphene was then directly obtained on SiO(2), eliminating
      any transfer process. The bilayer nature of the obtained graphene films on SiO(2)
      substrates was verified by Raman spectroscopy and transmission electron
      microscopy. The Raman spectroscopy mapping over a 100 * 100 MUm(2) area indicated
      that the obtained graphene is high-quality and bilayer coverage is approximately
      70%.

PMID- 21888425
TI  - Discovery of novel promising targets for anti-AIDS drug developments by computer
      modeling: application to the HIV-1 gp120 V3 loop.
AB  - The V3 loop on gp120 from HIV-1 is a focus of many research groups involved in
      anti-AIDS drug studies, because this region of the protein determines the
      preference of the virus for T-lymphocytes or primary macrophages. Although the V3
      loop governs cell tropism and, for this reason, exhibits one of the most
      attractive targets for anti-HIV-1 drug developments, its high sequence
      variability is a major complicating factor. Nevertheless, the data on the spatial
      arrangement of V3 obtained here for different HIV-1 subtypes by computer modeling
      clearly show that, despite a wide range of 3D folds, this functionally important
      site of gp120 forms at least three structurally invariant segments, which contain
      residues critical for cell tropism. It is evident that these conserved V3
      segments represent potential HIV-1 vulnerable spots and, therefore, provide a
      blueprint for the design of novel, potent and broad antiviral agents able to stop
      the HIV's spread.

PMID- 21888427
TI  - Cross-linking of interfacial layers affects the salt and temperature stability of
      multilayered emulsions consisting of fish gelatin and sugar beet pectin.
AB  - This study assessed the stabilizing effect of enzymatic cross-linking on double
      coated emulsions (beet pectin-fish gelatin). The beet pectin layer was cross
      linked via ferulic acid groups using laccase (an enzyme that is known to catalyze
      the oxidation of phenolic groups). Fish gelatin-coated oil droplets (primary
      emulsion) were mixed at pH 3.5 to promote electrostatic deposition of the beet
      pectin molecules onto the surfaces of the oil droplets (secondary emulsion).
      Laccase was then added to promote cross-linking of the adsorbed beet pectin
      layer. Cross-linked pectin-coated oil droplets had similar or significantly
      better stability (p < 0.05) than oil droplets of primary or secondary emulsions
      to NaCl addition (0-500 mM), CaCl(2) addition (0-250 mM), and thermal processing
      (30-90  degrees C for 30 min). Freeze-thaw stability and creaming behavior of
      enzyme-treated, secondary emulsions after two cycles (-8  degrees C for 22 h; 25 
      degrees C for 2 h) were significantly improved (p < 0.05). These results may have
      important implications for food manufacturers that are in need of emulsions with
      improved physical stability, for example, emulsions used in frozen foods for
      sauces or dips.

PMID- 21888429
TI  - Synthesis, structural transformation, thermal stability, valence state, and
      magnetic and electronic properties of PbNiO3 with perovskite- and LiNbO3-type
      structures.
AB  - We synthesized two high-pressure polymorphs PbNiO(3) with different structures, a
      perovskite-type and a LiNbO(3)-type structure, and investigated their formation
      behavior, detailed structure, structural transformation, thermal stability,
      valence state of cations, and magnetic and electronic properties. A perovskite
      type PbNiO(3) synthesized at 800  degrees C under a pressure of 3 GPa
      crystallizes as an orthorhombic GdFeO(3)-type structure with a space group Pnma.
      The reaction under high pressure was monitored by an in situ energy dispersive X
      ray diffraction experiment, which revealed that a perovskit-type phase was formed
      even at 400  degrees C under 3 GPa. The obtained perovskite-type phase
      irreversibly transforms to a LiNbO(3)-type phase with an acentric space group R3c
      by heat treatment at ambient pressure. The Rietveld structural refinement using
      synchrotron X-ray diffraction data and the XPS measurement for both the
      perovskite- and the LiNbO(3)-type phases reveal that both phases possess the
      valence state of Pb(4+)Ni(2+)O(3). Perovskite-type PbNiO(3) is the first example
      of the Pb(4+)M(2+)O(3) series, and the first example of the perovskite containing
      a tetravalent A-site cation without lone pair electrons. The magnetic
      susceptibility measurement shows that the perovskite- and LiNbO(3)-type PbNiO(3)
      undergo antiferromagnetic transition at 225 and 205 K, respectively. Both the
      perovskite- and LiNbO(3)-type phases exhibit semiconducting behavior.

PMID- 21888428
TI  - A novel alignment method and multiple filters for exclusion of unqualified
      peptides to enhance label-free quantification using peptide intensity in LC
      MS/MS.
AB  - Though many software packages have been developed to perform label-free
      quantification of proteins in complex biological samples using peptide
      intensities generated by LC-MS/MS, two critical issues are generally ignored in
      this field: (i) peptides have multiple elution patterns across runs in an
      experiment, and (ii) many peptides cannot be used for protein quantification. To
      address these two key issues, we have developed a novel alignment method to
      enable accurate peptide peak retention time determination and multiple filters to
      eliminate unqualified peptides for protein quantification. Repeatability and
      linearity have been tested using six very different samples, i.e., standard
      peptides, kidney tissue lysates, HT29-MTX cell lysates, depleted human serum,
      human serum albumin-bound proteins, and standard proteins spiked in kidney tissue
      lysates. At least 90.8% of the proteins (up to 1,390) had CVs <= 30% across 10
      technical replicates, and at least 93.6% (up to 2,013) had R(2) >= 0.9500 across
      7 concentrations. Identical amounts of standard protein spiked in complex
      biological samples achieved a CV of 8.6% across eight injections of two groups.
      Further assessment was made by comparing mass spectrometric results to
      immunodetection, and consistent results were obtained. The new approach has novel
      and specific features enabling accurate label-free quantification.

PMID- 21888430
TI  - Cell-permeable Ln(III) chelate-functionalized InP quantum dots as multimodal
      imaging agents.
AB  - Quantum dots (QDs) are ideal scaffolds for the development of multimodal imaging
      agents, but their application in clinical diagnostics is limited by the toxicity
      of classical CdSe QDs. A new bimodal MRI/optical nanosized contrast agent with
      high gadolinium payload has been prepared through direct covalent attachment of
      up to 80 Gd(III) chelates on fluorescent nontoxic InP/ZnS QDs. It shows a high
      relaxivity of 900 mM(-1) s(-1) (13 mM(-1 )s(-1) per Gd ion) at 35 MHz (0.81 T)
      and 298 K, while the bright luminescence of the QDs is preserved. Eu(III) and
      Tb(III) chelates were also successfully grafted to the InP/ZnS QDs. The absence
      of energy transfer between the QD and lanthanide emitting centers results in a
      multicolor system. Using this convenient direct grafting strategy additional
      targeting ligands can be included on the QD. Here a cell-penetrating peptide has
      been co-grafted in a one-pot reaction to afford a cell-permeable multimodal
      multimeric MRI contrast agent that reports cellular localization by fluorescence
      and provides high relaxivity and increased tissue retention with respect to
      commercial contrast agents.

PMID- 21888431
TI  - Is there a malignant progression associated with a linear change in protein
      expression levels from normal canine mammary gland to metastatic mammary tumors?
AB  - The molecular mechanisms of the development of canine mammary tumors are still
      incompletely understood. In the present study we hypothesized that there is a
      malignant progression from normal gland to malignant carcinomas that is
      associated with a linear change in protein expression. To this end, the proteome
      of canine normal mammary gland, adenomas, nonmetastatic carcinomas, and
      metastatic carcinomas was compared. Application of 2D-DIGE and MALDI-TOF-MS
      identified 48 proteins with significant changes (fold change >|1.5|; p < 0.05) in
      expression levels at the different stages of malignant progression. Forty-two of
      these followed three major stepwise but not linear expression patterns. Thirteen
      proteins showed the adenoma pattern characterized by a change in protein
      expression levels during progression from normal gland to adenomas which
      persisted on the same level at the subsequent stages of malignancy. Nine proteins
      followed the carcinoma pattern with an up- or down-regulation between adenomas
      and carcinomas. The majority of 20 proteins followed the metastasis pattern with
      a significant change of protein expression levels between nonmetastatic and
      metastatic carcinomas. The present study therefore shows that differences in
      malignancy are associated with a stepwise but not linear change in protein
      expression levels, which does not finally confirm or disapprove the existence of
      a malignant progression in canine mammary tumors. In addition, the acquisition of
      metastatic potential seems to be associated with the strongest changes in protein
      expression levels.

PMID- 21888432
TI  - Catalytic activities of subnanometer gold clusters (Au16-Au18, Au20, and Au27
      Au35) for CO oxidation.
AB  - Using the CO oxidation as a chemical probe, we perform a comprehensive ab initio
      study of catalytic activities of subnanometer gold clusters. Particular attention
      is placed on 12 different clusters in the size range of Au(16)-Au(35), whose
      atomic structures in the anionic state have been resolved from previous
      experiments. Adsorption energies of a single CO or O(2) molecule as well as
      coadsorption energies of both CO and O(2) molecules on various distinctive
      surface sites of each anionic cluster and their neutral counterpart are computed.
      In general, the anionic clusters can adsorb CO and O(2) more strongly than their
      neutral counterparts. The coadsorption energies of both CO and O(2) molecules
      decrease as the size of gold clusters increases with the exception of Au(34) (an
      electronic "magic-number" cluster). Besides the known factor of low coordination
      site, we find that a relatively small cone angle (<110 degrees ) associated with
      each surface site is another key geometric factor that can enhance the binding
      strength of CO and O(2). For the subnanometer clusters, although the size effect
      can be important to the strength of CO adsorption, it is less important to the
      activation energy. Using Au(34) as a prototype model, we show that strong CO and
      O(2) adsorption sites tend to yield a lower reaction barrier for the CO
      oxidation, but they have little effect on the stability of the reaction
      intermediate. Our calculations support the notion that CO and O(2) adsorption
      energies on the gold clusters can be an effective indicator to assess catalytic
      activities of subnanometer gold clusters. This systematic study of the site- and
      size-dependent adsorption energies and reaction pathways enables a quantitative
      assessment of the site-size-activity relationship for the CO oxidation on
      subnanometer gold clusters.

PMID- 21888433
TI  - Positive and negative photoion spectroscopy study of monochlorothiophenes.
AB  - Photolysis dynamics of monochlorothiophenes (2- and 3-chlorothiophenes) is
      investigated using positive and negative photoion mass spectrometry combined with
      the synchrotron vacuum ultraviolet radiation. A dozen of the daughter cations are
      observed in the time-of-flight mass spectra, and their appearance energies are
      determined by the photoion efficiency spectroscopy measurements. At the energetic
      threshold, the concerted process rather than a stepwise reaction for
      C(4)H(3)SCl(+) -> C(2)HSCl(+) + C(2)H(2) and the ring-open isomers of the
      dehydrogenated thiophene cations (C(4)H(3)S(+) and C(4)H(2)S(+)) formed in
      C(4)H(3)SCl(+) -> C(4)H(3)S(+) + Cl and C(4)H(2)S(+) + HCl are proposed on the
      basis of the B3LYP/6-311+G(3df,3pd) calculations. The chlorine anion (Cl(-)) is
      observed as the product of the photoion-pair dissociations in the energy range of
      10.70-22.00 eV. A set of valence-to-Rydberg state transitions 12a' -> np (n = 6,
      7, 8, 9, 10, etc.) and several series of vibrational excitations are tentatively
      assigned in the Cl(-) spectrum of 2-chlorothiophene in the lower energy range of
      10.90-12.00 eV.

PMID- 21888434
TI  - Ion-controlled on-off switch of electron transfer from tetrathiafulvalene
      calix[4]pyrroles to Li+@C60.
AB  - Binding of chloride anion to a tetrathiafulvalene calix[4]pyrrole (TTF-C4P) donor
      results in ET to Li(+)@C(60) to produce the radical pair (TTF
      C4P(*+)/Li(+)@C(60)(*-)), the structure of which was characterized by X-ray
      crystallographic analysis. The addition of tetraethylammonium cation, which binds
      more effectively than Li(+)@C(60)(*-) as a guest within the TTF-C4P cavity, leads
      to electron back-transfer, restoring the initial oxidation states of the donor
      and acceptor pair.

PMID- 21888436
TI  - Detection of allergenic ingredients using real-time PCR: a case study on hazelnut
      (Corylus avellena) and soy (Glycine max).
AB  - Compliance with the European allergen labeling legislation (Directive 2007/68/EC)
      is only possible when coupled with appropriate methods to detect allergens in
      food. The aim of the current study was to develop new real-time PCR assays for
      the detection of hazelnut and soy and evaluate these assays via comparison with
      commercially available kits. Although the new assays were not as sensitive as the
      commercial qualitative assays, they proved to be more specific. Moreover, the
      cross-reactivity study indicated contamination of some of the food products used
      with either hazelnut or soy, which presents a risk for the allergic consumer. The
      assays were able to quantify as few as 5-15 genome copies. This unit, used to
      express analytical results for allergen detection by means of PCR, needs to be
      converted to a unit expressing the amount of allergenic ingredient in order to be
      informative. This study emphasizes that the use of real-time PCR for allergen
      quantification is complicated by the lack of appropriate reference materials for
      allergens.

PMID- 21888435
TI  - Myosin binding protein-C slow is a novel substrate for protein kinase A (PKA) and
      C (PKC) in skeletal muscle.
AB  - Myosin Binding Protein-C slow (MyBP-C slow), a family of thick filament
      associated proteins, consists of four alternatively spliced forms, namely
      variants 1-4. Variants 1-4 share common structures and sequences; however, they
      differ in three regions: variants 1 and 2 contain a novel 25-residue long
      insertion at the extreme NH(2)-terminus, variant 3 carries an 18-amino acid long
      segment within immunoglobulin (Ig) domain C7, and variant 1 contains a unique
      COOH-terminus consisting of 26-amino acids, while variant 4 does not possess any
      of these insertions. Variants 1-4 are expressed in variable amounts among
      skeletal muscles, exhibiting different topographies and potentially distinct
      functions. To date, the regulatory mechanisms that modulate the activities of
      MyBP-C slow are unknown. Using an array of proteomic approaches, we show that
      MyBP-C slow comprises a family of phosphoproteins. Ser-59 and Ser-62 are
      substrates for PKA, while Ser-83 and Thr-84 are substrates for PKC. Moreover, Ser
      204 is a substrate for both PKA and PKC. Importantly, the levels of
      phosphorylated skeletal MyBP-C proteins (i.e., slow and fast) are notably
      increased in mouse dystrophic muscles, even though their overall amounts are
      significantly decreased. In brief, our studies are the first to show that the
      MyBP-C slow subfamily undergoes phosphorylation, which may regulate its
      activities in normalcy and disease.

PMID- 21888437
TI  - Chiral indolo[3,2-f][3]benzazecine-type dopamine receptor antagonists: synthesis
      and activity of racemic and enantiopure derivatives.
AB  - Racemic and enantiopure 8-substituted derivatives of the lead dopamine receptor
      antagonist LE 300 (1) were prepared, and their affinities for the dopamine
      receptors (D(1)-D(5)) were tested. The separate enantiomers showed significantly
      different affinities; the (8S)-methyl and (8R)-hyroxymethyl derivatives where the
      substituents point below the reference plane of the indolo[3,2-f][3]benzazecine
      scaffold were markedly more active than their enantiomeric counterparts. The
      racemic 8-carboxy derivative was shown to be selective for the D(5)-receptor,
      even against D(1).

PMID- 21888438
TI  - Molecular dynamics investigations of ozone on an ab initio potential energy
      surface with the utilization of pattern-recognition neural network for accurate
      determination of product formation.
AB  - The singlet-triplet transformation and molecular dissociation of ozone (O(3)) gas
      is investigated by performing quasi-classical molecular dynamics (MD) simulations
      on an ab initio potential energy surface (PES) with visible and near-infrared
      excitations. MP4(SDQ) level of theory with the 6-311g(2d,2p) basis set is
      executed for three different electronic spin states (singlet, triplet, and
      quintet). In order to simplify the potential energy function, an approximation is
      adopted by ignoring the spin-orbit coupling and allowing the molecule to switch
      favorably and instantaneously to the spin state that is more energetically stable
      (lowest in energy among the three spin states). This assumption has previously
      been utilized to study the SiO(2) system as reported by Agrawal et al. (J. Chem.
      Phys. 2006, 124 (13), 134306). The use of such assumption in this study probably
      makes the upper limits of computed rate coefficients the true rate coefficients.
      The global PES for ozone is constructed by fitting 5906 ab initio data points
      using a 60-neuron two-layer feed-forward neural network. The mean-absolute error
      and root-mean-squared error of this fit are 0.0446 eV (1.03 kcal/mol) and 0.0756
      eV (1.74 kcal/mol), respectively, which reveal very good fitting accuracy. The
      parameter coefficients of the global PES are reported in this paper. In order to
      identify the spin state with high confidence, we propose the use of a pattern
      recognition neural network, which is trained to predict the spin state of a given
      configuration (with a prediction accuracy being 95.6% on a set of testing data
      points). To enhance the prediction effectiveness, a buffer series of five points
      are validated to confirm the spin state during the MD process to gain better
      confidence. Quasi-classical MD simulations from 1.2 to 2.4 eV of total internal
      energy (including zero-point energy) result in rate coefficients of singlet
      triplet transformation in the range of 0.027 ps(-1) to 1.21 ps(-1). Also, we find
      very low dissociation probability up to 2.4 eV of internal energy during the
      investigating period (5 ps), which suggests that dissociation does not occur
      directly from the singlet ground-state, but it involves the excited triplet-state
      as an intermediate step and requires more reaction time to occur.

PMID- 21888439
TI  - Design and synthesis of inhaled p38 inhibitors for the treatment of chronic
      obstructive pulmonary disease.
AB  - This paper describes the identification and optimization of a novel series of DFG
      out binding p38 inhibitors as inhaled agents for the treatment of chronic
      obstructive pulmonary disease. Structure based drug design and "inhalation by
      design" principles have been applied to the optimization of the lead series
      exemplied by compound 1a. Analogues have been designed to be potent and selective
      for p38, with an emphasis on slow enzyme dissociation kinetics to deliver
      prolonged lung p38 inhibition. Pharmacokinetic properties were tuned with high
      intrinsic clearance and low oral bioavailability in mind, to minimize systemic
      exposure and reduce systemically driven adverse events. High CYP mediated
      clearance and glucuronidation were targeted to achieve high intrinsic clearance
      coupled with multiple routes of clearance to minimize drug-drug interactions.
      Furthermore, pharmaceutical properties such as stability, crystallinity, and
      solubility were considered to ensure compatibility with a dry powder inhaler. 1ab
      (PF-03715455) was subsequently identified as a clinical candidate from this
      series with efficacy and safety profiles confirming its potential as an inhaled
      agent for the treatment of COPD.

PMID- 21888440
TI  - Comparison of the reactivity of antimalarial 1,2,4,5-tetraoxanes with 1,2,4
      trioxolanes in the presence of ferrous iron salts, heme, and ferrous iron
      salts/phosphatidylcholine.
AB  - Dispiro-1,2,4,5-tetraoxanes and 1,2,4-trioxolanes represent attractive classes of
      synthetic antimalarial peroxides due to their structural simplicity, good
      stability, and impressive antimalarial activity. We investigated the reactivity
      of a series of potent amide functionalized tetraoxanes with Fe(II)gluconate,
      FeSO(4), FeSO(4)/TEMPO, FeSO(4)/phosphatidylcholine, and heme to gain knowledge
      of their potential mechanism of bioactivation and to compare the results with the
      corresponding 1,2,4-trioxolanes. Spin-trapping experiments demonstrate that
      Fe(II)-mediated peroxide activation of tetraoxanes produces primary and secondary
      C-radical intermediates. Reaction of tetraoxanes and trioxolanes with
      phosphatidylcholine, a predominant unsaturated lipid present in the parasite
      digestive vacuole membrane, under Fenton reaction conditions showed that both
      endoperoxides share a common reactivity in terms of phospholipid oxidation that
      differs with that of artemisinin. Significantly, when tetraoxanes undergo
      bioactivation in the presence of heme, only the secondary C-centered radical is
      observed, which smoothly produces regioisomeric drug derived-heme adducts. The
      ability of these tetraoxanes to alkylate the porphyrin ring was also confirmed
      with Fe(II)TPP and Mn(II)TPP, and docking studies were performed to rationalize
      the regioselectivity observed in the alkylation process. The efficient process of
      heme alkylation and extensive lipid peroxidation observed here may play a role in
      the mechanism of action of these two important classes of synthetic endoperoxide
      antimalarial.

PMID- 21888441
TI  - The worldwide opioid epidemic: implications for treatment and research in
      pregnancy and the newborn.

PMID- 21888442
TI  - Drug treatment of hypertensive crisis in children.
AB  - Hypertensive crisis is a relatively rare event and is associated with significant
      morbidity and mortality in adults and pediatric patients alike. Rapid, safe, and
      effective treatment is imperative to alleviate immediate presenting clinical
      symptoms, prevent devastating morbidity, preserve long-term quality of life, and
      prevent mortality. Many medications in the hypertensive crisis arsenal have been
      used for nearly half a century. Nearly all treatment options have been utilized
      in children for decades, yet reliable data and sound clinical literature remain
      elusive. Every agent considered to be a first-line, second-line, or adjunctive
      option has yet to be evaluated in a randomized controlled trial in pediatric
      patients. With a paucity of clinical data to form evidence-based decisions, the
      clinician must rely entirely on the extrapolation from adult data and small
      retrospective studies, case series, and case reports of medication use in
      pediatric patients. Although more research in the treatment of pediatric
      hypertensive crisis is desperately needed, current practice demands a sharp
      knowledge of the pediatric clinical literature and pharmacology in this area as
      an essential tool to consistently improve patient outcomes with respect to
      morbidity and mortality.

PMID- 21888443
TI  - Clinical usefulness of second-generation antipsychotics in treating children and
      adolescents diagnosed with bipolar or schizophrenic disorders.
AB  - The onset of severe, chronic or recurrent psychiatric illnesses, such as
      schizophrenia-spectrum and bipolar disorders, is a dramatic clinical event often
      detectable during adolescence and even in childhood. At any age, pharmacotherapy,
      along with enhancement of social skills and family support, is the mainstay for
      the management of such disorders. The aim of this review is to critically analyze
      findings from randomized controlled trials (RCTs) that have investigated the
      clinical utility of second-generation antipsychotics (SGAs) for the treatment of
      early-onset schizophrenia and bipolar disorders. Eighteen studies were
      considered, all of which were unfortunately impaired by methodologic limitations,
      such as the paucity of long-term data and lack of a three-arm comparison (SGA vs
      SGA vs placebo). Nevertheless, the results of this review allow us to suggest the
      effectiveness of three SGAs (aripiprazole, olanzapine, and risperidone) in the
      short-term treatment of both early-onset schizophrenia and bipolar mania,
      although such agents show different safety profiles. The use of clozapine should
      be strictly limited to patients with non-affective, psychotic symptoms who do not
      respond to any of these three SGAs. In contrast, the use of quetiapine and
      ziprasidone in young patients with either affective or non-affective psychosis is
      not yet supported by evidence-based information. Given our findings, further
      studies are urgently required to identify the best treatment option(s) for
      pediatric bipolar disorder (especially the depressive phase) and the long-term
      management of early-onset schizophrenia.

PMID- 21888444
TI  - Antiretroviral therapy for children in resource-limited settings: current
      regimens and the role of newer agents.
AB  - WHO antiretroviral treatment guidelines for HIV-infected children have influenced
      the design of treatment programmes in resource-limited settings. This review
      analyses the latest WHO first- and second-line regimen recommendations. The
      recommendation to use lopinavir/ritonavir-containing first-line regimens in young
      children with prior non-nucleoside reverse transcriptase inhibitor (NNRTI)
      exposure is based on good quality evidence. Recent research suggests that
      lopinavir/ritonavir-containing first-line regimens should be extended to all
      young children, irrespective of prior NNRTI exposure. Strategies for overcoming
      the adverse metabolic effects of rifampicin-containing anti-tuberculosis therapy
      on antiretroviral therapy regimens have been under-researched in HIV-infected
      children, creating uncertainty about global recommendations. Preferred second
      line recommendations are largely predictable. The exception is that NNRTI
      containing second-line regimens are recommended for children previously exposed
      to NNRTIs and who subsequently did not respond to lopinavir/ritonavir-containing
      first-line therapy. In these patients, second-line regimens containing newer
      protease inhibitors (PIs) such as darunavir and tipranavir, or integrase
      inhibitors such as raltegravir, should be evaluated. Newer antiretroviral agents
      including second-generation NNRTIs and PIs, C-C chemokine receptor type 5
      inhibitors, and integrase inhibitors may assist in further refinement of existing
      regimen options.

PMID- 21888445
TI  - Drug exposure during the periconceptional period: a study of 1793 women.
AB  - BACKGROUND: Many studies have described the prescribing of drugs to pregnant
      women, but only very few have data concerning the periconceptional period
      specifically. AIM: The aim of the study was to evaluate the incidence of exposure
      to teratogenic drugs during early pregnancy and to determine whether a safer drug
      exists. METHODS: In a French health insurances database, we analyzed drugs
      prescribed during the period starting 1 month before and ending 2 months after
      the beginning of pregnancy between 1 January 2006 and 31 December 2007. Based on
      the Summary of Product Characteristics (SPC), drugs we considered were those
      'contraindicated', 'not recommended', 'to be avoided', and 'possible' for use
      during the first trimester of pregnancy. For drugs 'contraindicated', we
      established if there were alternatives with similar efficacy for the mother and
      lower risk for the fetus. RESULTS: Over a period of 2.25 years, 8754 drugs were
      prescribed to 1793 women starting 1 month prior to and ending 2 months after
      conception. Among these drugs, 20 (0.2%) were 'contraindicated', 195 (2.2%) were
      'not recommended', and 1209 (13.8%) were 'to be avoided' during the first
      trimester of pregnancy. Twenty (1.1%) women received at least one drug that was
      'contraindicated' during the first trimester, 171 (9.5%) received a drug that was
      'not recommended' and 768 (42.8%) received a drug that was 'to be avoided'. At
      least one possible alternative was available for all except one 'contraindicated'
      drug. CONCLUSIONS: During the highest teratogenic risk period, 1.1% of women
      received a contraindicated drug, despite existence of a safer alternative drug.
      This may be partly accounted for by physicians not being aware of the pregnancy
      at the time the drug was administered and could be reduced by adding a section
      entitled 'women of child-bearing potential' to the SPC.

PMID- 21888446
TI  - 47th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago,
      IL, USA, 3-7 June 2011: focus on Pediatric Oncology.

PMID- 21888447
TI  - Clonidine extended-release: in attention-deficit hyperactivity disorder.
AB  - Clonidine, an alpha(2)-adrenergic agonist, is approved in the US as an extended
      release (XR) tablet for the treatment of attention-deficit hyperactivity disorder
      (ADHD) in children and adolescents (aged 6-17 years). In two, randomized, double
      blind, multicenter, phase III trials of 8 weeks' duration, clonidine XR improved
      the symptoms of ADHD in children and adolescents. Significantly greater
      reductions from baseline in ADHD rating scale IV (ADHD-RS-IV) total scores at
      week 5 (primary endpoint) were achieved by recipients of clonidine XR 0.2 and 0.4
      mg/day monotherapy than by recipients of placebo. When added to patients' normal
      stimulant regimen, significantly greater reductions from baseline in ADHD-RS-IV
      total scores at week 5 (primary endpoint) were achieved with a flexible dose of
      clonidine XR 0.1-0.4 mg/day than with placebo. Symptomatic improvement of ADHD
      was achieved following 2 weeks' treatment with clonidine XR. In both trials,
      significantly greater reductions from baseline in ADHD-RS-IV total scores were
      apparent at week 2 onwards for recipients of clonidine XR than for recipients of
      placebo. Clonidine XR was generally well tolerated as monotherapy and as
      adjunctive therapy with stimulant regimens in clinical trials in children and
      adolescents.

PMID- 21888448
TI  - 17 alpha-Hydroxyprogesterone caproate (MakenaTM): in the prevention of preterm
      birth.
AB  - 17 alpha-hydroxyprogesterone caproate is a synthetic progestin of which there is
      now a US FDA-approved formulation available for intramuscular administration
      (MakenaTM) to reduce the risk of preterm birth. Intramuscular 17 alpha
      hydroxyprogesterone caproate (identical in formulation and manufacturing process
      to MakenaTM, thus hereafter referred to as MakenaTM) 250 mg once weekly,
      initiated at 16-20 weeks' gestation, was effective in reducing the risk of
      preterm birth in women with a singleton pregnancy at high risk of delivering
      preterm in a large, well designed, placebo-controlled trial (n = 463 randomized).
      Rates of delivery before 37 (primary endpoint), 35, or 32 weeks' gestation were
      significantly lower with MakenaTM than with placebo, corresponding to relative
      risk reductions of 34%, 33%, and 42%, respectively. The benefit of the drug in
      reducing the risk of preterm birth was observed when deliveries were spontaneous
      (but not when indicated because of complications) and regardless of maternal
      race. In addition, there was a significantly lower rate of several adverse
      fetal/neonatal outcomes among infants of women who received MakenaTM than among
      infants of placebo recipients, including necrotizing enterocolitis, need for
      supplemental oxygen, birth weight of <2500 g, and intraventricular hemorrhage.
      MakenaTM was generally well tolerated in pregnant women in this trial. Moreover,
      fetal exposure to the drug appeared to be safe according to a 2- to 5-year follow
      up of the study, with no evidence of a detrimental effect of the drug on child
      neurodevelopment and a low overall incidence (~2%) of reproductive or genital
      abnormalities that was not significantly different from placebo.

PMID- 21888449
TI  - Excess costs associated with patients with chronic thromboembolic pulmonary
      hypertension in a US privately insured population.
AB  - BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and
      potentially fatal disease. Little is known about the economic burden associated
      with CTEPH patients in the US. OBJECTIVES: The objective of this study was to
      estimate excess direct costs associated with privately insured patients with
      CTEPH in the US. METHODS: From a privately insured claims database (>8 million
      beneficiaries, 2002-7), 289 CTEPH patients were identified using the criteria:
      two or more claims for pulmonary hypertension (PH), International Classification
      of Diseases, ninth edition, clinical modification (ICD-9-CM) code 416.0 or 416.8;
      one or more claim for pulmonary embolism (ICD-9-CM: 415.1, V12.51; ICD-9
      procedure: 38.7; Current Procedural Terminology [CPT]-4 code: 36010, 37620,
      75825, 75940; Healthcare Common Procedure Coding System [HCPCS] code: C1880)
      within 12 months prior or 1 month after the initial PH claim (index date); one or
      more claim for right heart catheterization (RHC) within 6 months prior to any PH
      claim or one or more claim for echocardiogram within 6 months prior to a
      specialist-diagnosed PH claim; aged 18-64 years. Patients with CTEPH were matched
      demographically to controls without PH. Patients were followed as long as
      continuously eligible; mean follow-up in CTEPH patients was 21.5 months. Chi
      squared tests were used to compare baseline co-morbidities. Wilcoxon rank-sum
      tests were used to compare direct (medical and pharmaceutical) patient-month
      costs to insurers. RESULTS: The average age for CTEPH patients was 52.2 years,
      and 57.1% were women. Compared with controls, CTEPH patients had significantly
      higher baseline rates of co-morbidities (e.g. essential hypertension, congestive
      heart failure and chronic pulmonary disease) and a higher mean Charlson Co
      morbidity Index score. Mean direct patient-month costs (year 2007 values) were
      $US4782 for CTEPH patients and $US511 for controls (p < 0.0001). Sensitivity
      analysis restricting the sample to patients diagnosed following RHC yielded a 15%
      increase in excess costs relative to the original sample. Regarding cost drivers,
      inpatient services accounted for 54%, outpatient and other services for 33% and
      prescription drugs for 11% of total direct healthcare costs per patient-month in
      CTEPH patients. Circulatory-/respiratory-related patient-month costs were $US2496
      among CTEPH patients and $US128 among controls (p < 0.0001). CONCLUSIONS: CTEPH
      patients had substantially higher costs and co-morbidity than matched controls,
      with circulatory-/respiratory-related costs accounting for 55% of excess costs.
      The high burden of illness suggests opportunities for savings from improved
      management.

PMID- 21888450
TI  - Erythroid disturbances before and after treatment of Portuguese psoriasis
      vulgaris patients: a cross-sectional and longitudinal study.
AB  - BACKGROUND: A few studies in psoriasis vulgaris patients have reported changes
      suggesting red blood cell (RBC) damage is linked to neutrophil activation,
      oxidative stress, and psoriasis worsening. OBJECTIVE: The aim of this study was
      to evaluate erythroid disturbances in Portuguese psoriasis vulgaris patients,
      before, during, and after treatment. METHODS: A cross-sectional study (n = 73
      patients vs 40 healthy control subjects) followed by a longitudinal study (n = 47
      patients) was performed, with assessments before, and at 3, 6, and 12 weeks of
      therapy (10 patients started topical treatment, 17 narrow-band UVB, and 20
      photochemotherapy [psoralen plus UVA; PUVA]). Evaluations included hematologic
      data, total bilirubin levels, membrane-bound hemoglobin (MBH), membrane protein
      band 3 profile, total plasma antioxidant status (TAS), lipid peroxidation
      (thiobarbituric acid [TBA] assay), elastase, lactoferrin, and C-reactive protein
      (CRP). RESULTS: Before treatment, patients presented with higher
      leukocyte/neutrophil and reticulocyte counts, elastase, lactoferrin, TBA,
      TBA/TAS, reticulocyte production index, total bilirubin and MBH values, lower RBC
      and hematocrit, higher percentages of high-molecular-weight aggregates, and lower
      percentages of band 3 monomer. After treatment, we observed a reversal in most of
      the parameters. However, patients still presented with values suggestive of
      accelerated RBC damage, removal, and production, as most of the parameters were
      still higher than those in the control group; the same occurred with CRP.
      CONCLUSION: Our data suggest that psoriasis vulgaris triggers an inflammatory
      response, with release of acute-phase reactants, reactive oxygen species,
      cationic proteins, and proteases, leading to enhanced RBC damage/aging and,
      ultimately, to enhanced RBC removal. These assumptions were strengthened by the
      observation that, with treatment, all of these changes were reversed, the
      inflammation was reduced, the production of reticulocytes was increased, and the
      RBCs presented changes usually observed in younger/less damaged RBCs. These
      erythroid changes were enhanced with PUVA therapy, probably due to the more
      pronounced clearing of the lesions, as suggested by Psoriasis Area and Severity
      Index (PASI) scores. Finally, after treatment, a residual inflammation still
      persisted that might contribute to the observed erythroid disturbances.

PMID- 21888452
TI  - Geopolitical changes and trends in Middle Eastern countries' contributions to
      world science over the past three decades.

PMID- 21888451
TI  - Amphotericin B lipid complex in the management of invasive fungal infections in
      immunocompromised patients.
AB  - Invasive fungal infections are associated with a poor outcome and their incidence
      is rising. Amphotericin B has for a long time been the gold standard for
      treatment of these infections, but the conventional formulation is associated
      with a high incidence of adverse events. Lipid formulations of amphotericin,
      developed to overcome these drawbacks, are now routinely used in clinical
      practice for the treatment of invasive fungal infections in immunocompromised
      patients. Amphotericin B lipid complex (ABLC) is prepared from amphotericin
      complexed to two phospholipids, a process that confers a number of important
      pharmacodynamic and pharmacokinetic properties compared with conventional
      amphotericin B. The results of retrospective observational studies and the
      analysis of databases, including the large Collaborative Exchange of Antifungal
      Research (CLEAR) database, have shown ABLC to be associated with response rates
      of up to about 80% in patients with confirmed fungal infections and around 60% in
      those treated empirically. Intranasal administration of ABLC for prophylaxis of
      invasive fungal infection in immunocompromised patients is safe and appears to be
      a promising treatment strategy for the future. ABLC is associated with a
      substantially lower incidence of nephrotoxicity than conventional amphotericin.
      Infusion-related reactions also occur less frequently than with conventional
      amphotericin and can be managed using premedication protocols. When direct and
      indirect costs are measured, ABLC appears to be less expensive than conventional
      amphotericin. The number of approved antifungal agents that are effective
      treatments for invasive fungal infections is increasing. However, lipid
      formulations of amphotericin, such as ABLC, are effective and well tolerated and
      remain the standard of care in the treatment of invasive fungal infections.
      Treatment strategies such as intranasal administration for prophylaxis and
      combination therapy with newer agents are future directions for these agents.

PMID- 21888453
TI  - Dietary nitrate may have a role in development of gastro-esophageal reflux
      disease.
AB  - BACKGROUND: Gastro-esophageal reflux disease (GERD) has become very common in the
      past three decades. The reason for this, as well as its exact pathophysiologic
      mechanisms are yet unknown. In this ecologic study we assessed the relation
      between water nitrate content and prevalence of GERD in Tehran, Iran. METHODS: We
      determined the prevalence of acid regurgitation, heartburn or any of them
      occurring on a frequent (at least weekly) or infrequent basis in areas with
      different water nitrate. The areas for nitrate were defined as below: <50 mg
      nitrate/L, 50-74 mg/L, 75-100 mg/L, and >100 mg/L. Frequency of each symptom was
      assessed in each area and compared. Adjustment for age, sex, education, NSAID
      consumption, BMI, smoking, history of GERD in first degree relatives and spouse
      was done in a multivariate model. RESULTS: People living in areas with water
      nitrate content more than 100mg/L had a higher chance of suffering from frequent
      AR than those living in areas with water nitrate less than 100mg/L (25.5% vs.
      12.0%, OR: 2.53, 95% CI: 1.36-4.73, P=0.006). After adjustment for the named
      factors, the relationship remained significant (OR: 3.65, 95% CI: 1.32-10.09).
      The relation for frequent heartburn or infrequent symptoms was not significant.
      CONCLUSION: In this ecologic study, we found a relation between experiencing
      frequent AR and drinking or cooking with water containing more than 100mg
      nitrate/L. Considering our current knowledge, if we put dietary nitrate into the
      puzzle of increased prevalence and/or pathophysiology of GERD, it can
      theoretically answer several questions. Hence we propose a nitrate-hypothesis for
      GERD pathogenesis.

PMID- 21888454
TI  - Asthma knowledge, attitude, and self-efficacy in Iranian asthmatic patients.
AB  - BACKGROUND: Worldwide, numerous people of all ages and ethnicities experience
      asthma. The achievements of current medical regimens for patients frequently
      depend on three factors: 1) knowledge of patients regarding this disease, 2)
      patient's attitude about asthma, including willingness to collaborate with the
      therapeutic group for disease control and 3) patient's self-efficacy for
      controlling asthma. Therefore, this study examined the relationship between
      knowledge, attitudes, and self-efficacy with socio-economic factors in Iranian
      asthmatic patients during 2006-2008. METHODS: Participants consisted of 120
      adults referred to Milad Hospital, Tehran, Iran during 2006 to 2008 whose
      physicians diagnosed their asthma. Socio-demographic factors such as sex, age,
      education level, occupation, marital status, family history of asthma, disease
      costs, and period of sickness were reviewed. Assessments of knowledge, attitudes
      and self-efficacy were performed by the Persian version of an international
      standard questionnaire (KASE-AQ). Data were analyzed by SPSS version 14. RESULTS:
      Among respondents, only 9 (7.5%) patients had good knowledge about asthma, 108
      (90%) patients had a suitable attitude about their asthma and 103 (85.3%)
      patients had proper self-efficacy. We found a significant association between
      self-efficacy and attitude in asthmatic patients (P<0.05). CONCLUSION: Although
      specific knowledge about asthma is low, however, favorable attitudes toward
      asthma create opportunities to intervene and improve asthma management among
      patients. However, the use of educational tools depends on patients' educational
      levels. Therefore, we recommend elevating asthma knowledge.

PMID- 21888455
TI  - Molecular cytogenetic analysis of chemoresistant non-Hodgkin's lymphoma patients
      with p53 abnormalities using fluorescence in situ hybridisation and comparative
      genomic hybridisation.
AB  - BACKGROUND: Alterations of the p53 gene at 17p13.1 as well as the gene for a
      transmembrane p-glycoprotein, ABCB1 (MDR-1) at 7q21.12, have been shown to be
      mostly associated with the phenomenon of multi-drug resistance (MDR) in human
      cancers. In order to better understand the mechanisms by which chemoresistance is
      mediated, non-hodgkin's lymphoma (NHL) patients overexpressing p53 mutant protein
      and resistant to CHOP chemotherapy, NHL patients without p53 overexpression and a
      Burkitt's lymphoma Raji cell line with p53 overexpression have been evaluated
      using fluorescent in situ hybridization (FISH) and comparative genomic
      hybridization (CGH). METHODS: Three chromosomes (1, 7, and 17) known to be
      associated with MDR and the presence of p53 mutant protein, were analysed by
      FISH. RESULTS: No obvious chromosomal aberrations such as translocations were
      found in any of the patients when compared to healthy individuals, which suggests
      that the three selected chromosomes might not be specifically related to NHL,
      with or without p53 overexpression. For CGH, gains and losses of chromosomal
      material have been identified and the changes were not only limited to the three
      selected chromosomes associated with MDR. A detailed analysis of the recurrent
      aberrations shows that most of the NHL patients have alterations on the
      chromosome arms 1p, 6q, 7q, 20q, 22q, and Xp, whereas patients with p53
      overexpression predominantly show aberrations on 4p and 17q. CONCLUSION: Further
      characterisation of the genetic regions identified might more closely contribute
      to our understanding of acquired MDR in NHL. Alterations in the three evaluated
      chromosomes may be prevalent in other tumours. In the present study, using FISH
      and CGH, there was insufficient difference between NHL patients with and without
      p53 overexpression.

PMID- 21888456
TI  - Psychometric properties of a modified version of the Roland-Morris disability
      questionnaire (M-RMDQ).
AB  - BACKGROUND: Chronic pain can be associated with limitations in patient function.
      Assessment of pain-related limitations is one of the important outcome domains
      that should be considered when designing chronic pain clinical trials. Although a
      validated instrument for the assessment of pain-related disability in Iranian
      chronic low back pain (CLBP) patients exists, to date there is no
      psychometrically sound instrument to measure pain-related physical disability
      amongst Iranian chronic pain patients suffering from pain in other parts of their
      bodies. METHODS: Six hundred chronic pain patients completed the Modified version
      of the Roland-Morris disability questionnaire (M-RMDQ) in addition to
      questionnaires on demographic variables, pain intensity and depression. RESULTS:
      Internal consistency, test-retest reliability, and concurrent and predictive
      validity were calculated for the M-RMDQ. Internal consistency of the M-RMDQ items
      was acceptable (Cronbach's alpha=0.88). Test-retest reliability with a mean 36
      day interval between assessments in 76 chronic pain patients was high (ICC=0.90).
      Concurrent validity was confirmed via significant correlations between the scores
      of M-RMDQ, depression and pain intensity. Predictive validity of the M-RMDQ was
      confirmed as it successfully differentiated pain clinic chronic pain patients
      from the non-pain clinic chronic pain population. CONCLUSION: The M-RMDQ has
      adequate reliability and validity and can be used as a sound measure of physical
      disability associated with chronic pain among the Iranian population.

PMID- 21888457
TI  - Hematopoietic stem cell transplantation in acute promyelocytic leukemia,
      experience in Iran.
AB  - BACKGROUND: Acute promyelocytic leukemia is a rare indication for hematopoietic
      stem cell transplantation. Usually it is indicated as consolidation of salvage
      regimens following relpase. Here we report our experience with stem cell
      transplantation in acute promyelocytic leukemia patients. METHODS: Between 1989
      and 2011, we performed 40 hematopoietic stem cell transplantation in first
      complete remission or relapsed acute promyelocytic leukemia patients. Median age
      of patients was 23.5 years. Patients received 11 autologous and 29 allogeneic
      hematopoietic stem cell transplantation from their HLA fully-matched sibling
      donors. Different conditioning regimens were applied. A total of 24 patients
      received hematopoietic stem cell transplantation who were in first complete
      remission and the remainder with a second or more complete remission. RESULTS:
      Hematopoietic stem cell engraftment was observed in all cases. There were no
      deaths prior to 100 days after hematopoietic stem cell transplantation. Acute
      graft versus host disease was mild to moderate in the majority of patients,
      whereas it was grade III in 4 patients. Chronic graft versus host disease was
      extensive in 2 cases. With a 4-year median follow up, the relapse rate was 25%. A
      total of 26 patients are alive. Five year overall survival was 65.5% and 46.8%
      for allogeneic and autologous hematopoietic stem cell transplantation,
      respectively. CONCLUSION: Hematopoietic stem cell transplantation is an
      acceptable treatment for acute promyelocytic leukemia. Although there is a
      statistical difference for overall survival between allogeneic or autologous
      hematopoietic stem cell transplantation, the choice between autologous or
      allogeneic transplantation needs to have reliable methods for the detection of
      molecular remission before hematopoietic stem cell transplantation as well as
      close, reliable follow up of patients with clinical and molecular parameters.

PMID- 21888458
TI  - Prevalence of symptoms and risk of obstructive sleep apnea syndrome in the
      general population.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) syndrome is one of the most common
      sleep breathing disorders with significant consequences. The present study aims
      to determine prevalence of symptoms and risk of OSA in the general population of
      Kermanshah, Iran. METHODS: From 2007-2008 by random-cluster-sampling, 527 adult
      subjects were selected from the urban region of Kermanshah. The age range of the
      sample was from 20 to 87 years. Assessment was carried-out using the Berlin
      questionnaire, a valid scale that determined those at "high risk" and "low risk"
      for OSA symptoms. Common symptoms were later defined.  RESULTS: There were 144
      (27.3%) out of the 527 subjects with a mean age of 48.6+/-16.6 years and a body
      mass index (BMI) of 25.1+/-3.3 at high risk for OSA (men 19%; women 8.3%); 261
      (49.5%) suffered from snoring with a higher frequency among women (51.5%). From
      those who snored during sleep, 51 (10%) reported a breathing pause more than once
      per week. Subjects considered at high risk had a clinical history of diabetes
      (15.3%) and heart failure (16.7%). CONCLUSION: Prevalence of symptoms, risk of
      OSA and associated factors in Kermanshah are noticeable. Considering the adverse
      effects of this condition on quality of life, further research in an effort for
      early diagnosis and treatment are recommended.

PMID- 21888459
TI  - A cholera outbreak associated with drinking contaminated well water.
AB  - BACKGROUND: Cholera has been a significant public health challenge in many
      communities. An outbreak of acute diarrheal illness occurred among participants
      in a wedding ceremony in a village in Qazvin, Iran, in 2008. We conducted an
      epidemiological, environmental and microbiological investigation to determine the
      causative agent, source and extent of this outbreak. METHODS: Clinical and
      environmental samples were collected and analyzed for the presence of diarrhea
      causing bacterial organisms, which included Vibrio cholera. The relationship
      between the strains was determined using enterobacterial repetitive intergenic
      consensus polymerase chain reaction (ERIC-PCR). RESULTS: The attack rate was
      21.8%. Clinical and environmental samples were positive for V. cholerae serotype
      Inaba. All tested isolates had a similar ERIC-PCR pattern, which indicated that a
      single clone of V. cholerae was responsible for this outbreak. CONCLUSION: Our
      findings demonstrated that well water was the source of this outbreak.

PMID- 21888460
TI  - Diagnosis and management of venous thromboembolism: an update a decade into the
      new millennium.
AB  - Venous thromboembolism refers to thrombotic events in the venous system that are
      most commonly manifested as deep vein thromboses in the upper or lower extremity
      and/or pulmonary embolism. Venous thromboembolism is a common disorder that is
      associated with significant mortality, morbidity and health care-related cost. An
      array of hereditary and acquired risk factors are associated with venous
      thromboembolism. In recent years, a number of pivotal studies have expanded our
      understanding of the pathophysiology of venous thromboembolism, and served as the
      basis for evidence-based guidelines on prevention, diagnosis and treatment of
      venous thromboembolism. Furthermore, several novel therapeutic agents with
      different pharmacokinetics, pharmacodynamics and safety profiles have recently
      become available for treatment and prevention of venous thromboembolism. The
      purpose of the current paper is to review the pathogenesis and epidemiology of
      venous thromboembolism as well as an evidence-based approach to the diagnosis and
      management of venous thromboembolism.

PMID- 21888461
TI  - Validity of bone mineral density and WHO fracture risk assessment thresholds in
      hip fractures.
AB  - Hip fractures are common and serious consequence of osteoporosis. Bone mineral
      density (BMD) measurement and the World Health Organization (WHO) fracture risk
      assessment tool are considered to predict the hip osteoporotic fractures. In this
      study, their sensitivities in hip fracture cases are evaluated. BMD and WHO
      probability of fracture risk were determined in 71 hip fractures >= 50 years of
      old. Totally, 65% of patients had <=-2.5 BMD T score. 81% of patients had above
      the upper interventional threshold of WHO fracture risk probability model.
      Sensitivities were low in 50-59 year age group with progression in older age
      groups. Results of BMD T score and fracture risk probabilities were not
      significant between men and women. There were 23% and 49% sensitivities of less
      than or equal to -2.5 T score in the 50-59 and 60-69 year age groups with a 31%
      sensitivity of greater than 3% probability of hip fracture risk in the 50-59 year
      age group, both of which were not valid for predicting hip fracture risk.

PMID- 21888462
TI  - Congenital arhinia: case report of a rare congenital anomaly.
AB  - Congenital absence of the nose or arhinia is a rare defect of embryogenesis often
      associated with other anomalies. Arhinia is a life-threatening condition that
      requires a highly skilled neonatal resuscitation team in the delivery room. The
      associated anomalies often have a significant effect on the immediate as well as
      long-term outcome of the neonate. This report presents a case of congenital
      arhinia and reviews the management of such cases.

PMID- 21888463
TI  - Obstructive and inflammatory gastric heterotopic pancreatic tissue.
AB  - Heterotopic pancreas is defined as pancreatic tissue arising ectopically with no
      vascular or anatomic contiguity with the pancreas proper and is believed to arise
      embryologically during rotation of the foregut and fusion of the dorsal and
      ventral pancreatic buds. We report a case of gastric heterotopic pancreas
      presenting as an obstructive inflammatory mass with the clinical differential
      diagnosis of gastric carcinoma. A 54 year-old woman presented with a history of
      four days of severe, acute-onset abdominal pain. Abdominal ultrasound showed a
      gastric antral mass. This was confirmed on computerized tomography, which
      revealed a hypo-dense mass with heterogeneous enhancement in the gastric antrum
      and multiple ill-defined hypo-dense areas in the liver suspicious for metastases.
      A preoperative diagnosis of malignant neoplasm was strongly favored, and a
      subtotal gastrectomy was performed. Microscopic examination of the specimen
      revealed submucosal and deeply seated intra-muscular and mural heterotopic
      pancreatic tissue, comprised of both ductal and acinar structures, surrounded by
      exuberant acute and chronic inflammation. The ducts were inflamed and showed
      marked cytologic atypia, favored to be of reactive nature. There was overlying
      mucosal ulceration with marked acute and chronic full-thickness gastric mural
      inflammatory response with abscess formation. This is the second reported case of
      obstructive gastric heterotopic pancreas, presenting as an inflammatory mural
      gastric mass.

PMID- 21888464
TI  - Photoclinic. Pedunculated facial hemangioma in an adult.

PMID- 21888466
TI  - Lower fasting plasma glucose criteria and high triglycerides are effective for
      screening diabetes mellitus in the rural Japanese population: the Tottori-Kofu
      Study.

PMID- 21888468
TI  - Well-woman care among obstetrician-gynecologists: opportunity for preconception
      care.
AB  - OBJECTIVE: To describe the practices of obstetrician-gynecologists who provide
      routine gynecological care and assess the relative importance of well-woman care
      to their training and practices. METHODS: A questionnaire was mailed to 1000
      members of the American College of Obstetricians and Gynecologists, of whom 600
      participated in the Collaborative Ambulatory Research Network. RESULTS: The
      response rate was 57%. Of these, 403 respondents providing routine obstetric and
      gynecologic care (OB&Gyn) are included. Obstetricians-gynecologists spend the
      majority of their time on labor/delivery (22%) followed by well-woman care (14%).
      It was found that 26% of the respondents rarely or never discuss sexual abuse or
      domestic violence with non-pregnant patients and only 19% always discuss folic
      acid with non-pregnant patients during well-woman care. Most (71%) say that 50%
      or more of their pregnant patients initially contact them once they are pregnant.
      Respondents rated their training in well-woman care least strong of several areas
      listed. CONCLUSION: Obstetrician-gynecologists devote a substantial proportion of
      work time to providing well-woman care, though some important topics are not
      addressed and training in this area was rated least strong.

PMID- 21888469
TI  - Expression of WT1 during normal human kidney development.
AB  - Wilms Tumor 1 (WT1) is a zinc finger protein, expressed by human podocytes in the
      adult kidney, which plays a relevant role in different phases of nephrogenesis in
      experimental animals. Since no data are available for specific role in the human
      fetal kidney, this study aimed at investigating the expression of WT1 during the
      different phases of nephrogenesis. To this end, the expression of WT1 was
      evaluated in the kidneys, from four human fetuses and two newborns. WT1
      immunoreactivity was detected in all the examined kidneys, but not in the kidneys
      of the newborn at term. Immunostaining for WT1 was observed in podocytes of the
      glomeruli and in the subcapsular regions, in areas of active glomerulogenesis.
      The extent and the intensity of immunoreactivity for WT1 changed from one case to
      the next according to the different gestational age. This study confirms in human
      kidney the relevant role played by WT1 during nephrogenesis. Its expression
      pattern suggests a main role in the regulation of the process of Mesenchimal
      Epithelial-Transition and in the development and maturation of podocytes. Further
      studies are needed to verify the correlation between the expression pattern of
      WT1 and that of other genes products involved in nephrogenesis, in order to
      better understand their relationship at protein level.

PMID- 21888470
TI  - Chinese children at a crossroads: influence of family socioeconomic factors on
      diet patterns.
AB  - This pilot study explores the roles of family socioeconomic status (SES) in
      influencing dietary consumption patterns in 60 Chinese elementary school-aged
      children (ages 6-11) in Chengdu, China. Two interviewer-administered
      questionnaires were specially developed to gather sociodemographic and food
      frequency data. Children from low SES families consumed rice and traditional
      staples, and high calcium drinks more frequently, and western fast food less
      frequently than children from higher SES families. After controlling for family
      SES, children who were primarily cared for by their mothers or grandparents
      consumed less healthy snacks less frequently than children who were primarily
      cared for by other adults (including fathers).

PMID- 21888471
TI  - Dietary non-heme iron bioavailability among children (ages 5-8) in a rural, high
      anemia-prevalent area in North India: comparison of algorithms.
AB  - Non-heme iron bioavailability of diet consumed by children (ages 5 to 8) in rural
      area of India was estimated by comparison of algorithms. A cross-sectional
      observational study was conducted among 232 children and consisted of a 24-hour
      recall on 2 nonconsecutive days. Four algorithms were chosen to estimate the non
      heme iron bioavailability. Daily average non-heme iron bioavailability as
      calculated by different algorithms was low (between 3.2% and 4.6%). Correlations
      of bioavailable non-heme iron among different algorithms were strong, ranging
      from rs = 0.67 to rs = 0.85 (p <= .01).

PMID- 21888472
TI  - Three traditional fermented baobab foods from Benin, Mutchayan, Dikouanyouri, and
      Tayohounta: preparation, properties, and consumption.
AB  - Forest food resources contribute significantly to food supply in areas where they
      grow. Three fermented baobab foods were studied: Dikouanyouri (from seeds, pH =
      6.5); Tayohounta (from seed kernels, pH = 7), and Mutchayan (from baobab pulp and
      sorghum, pH = 4.2). Bacillus spp. (8.5 and 9.5 Log cfu /g) and lactic acid
      bacteria (8.9 and 8.4 Log cfu /g,) dominate in Dikouanyouri and Tayohounta,
      respectively. In Mutchayan, lactic acid bacteria (8.1 Log cfu/g) and yeasts (7.2
      Log cfu/g) predominated. The arbitrary index of protein cleavage increases from
      2.3% (unfermented products) to 13.7% in Dikouanyouri and 21.3% in Tayohounta,
      indicating significant protein degradation. Mutchayan is the most frequently
      consumed product.

PMID- 21888473
TI  - Factors affecting rabbit meat consumption among Spanish university students.
AB  - This study investigates the rabbit meat consumption patterns among students.
      Results of the 342 students surveyed at the University of Seville, Spain showed
      that more men than women consumed rabbit meat. More students consumed wild rabbit
      meat than farmed rabbit meat. The practice of hunting by students or their
      relatives, and the raising of rabbits for self-consumption, positively influenced
      the proportion of students that currently consumed rabbit meat. Most of the
      students that had eaten rabbit meat before but are currently non-eaters do so
      because of the meat's organoleptic characteristics or from lack of consumption
      habit.

PMID- 21888474
TI  - Healthy habits or damaging diets: an exploratory study of a food blogging
      community.
AB  - This exploratory study describes the virtual socialization, behaviors, and
      attitudes being promoted in one community of food bloggers. Two months of entries
      from 45 blogs created by young women belonging to a photography-based food
      blogging community were analyzed and coded using a qualitative approach. Analysis
      revealed widespread group practices as well as the promotion of attitudes and
      behaviors associated with dietary restraint. The present study highlights the
      need for further research using food-blogging communities, and concludes with a
      cautionary note about blogs as sources of health information in view of the
      consequences of dietary restraint.

PMID- 21888476
TI  - Is postoperative intensive care unit admission a prerequisite for elective
      craniotomy?
AB  - OBJECT: Routine postoperative admission to the intensive care unit (ICU) is often
      considered a necessity in the treatment of patients following elective craniotomy
      but may strain already limited resources and is of unproven benefit. In this
      study the authors investigated whether routine postoperative admission to a
      regular stepdown ward is a safe alternative. METHODS: Three hundred ninety-four
      consecutive patients who had undergone elective craniotomy over 54 months at a
      single institution were retrospectively analyzed. Indications for craniotomy
      included tumor (257 patients) and transsphenoidal (63 patients), vascular (31
      patients), ventriculostomy (22 patients), developmental (13 patients), and base
      of skull conditions (8 patients). Recorded data included age, operation, reason
      for ICU admission, medical emergency team (MET) calls, in-hospital mortality, and
      postoperative duration of stay. RESULTS: Three hundred forty-three patients were
      admitted to the regular ward after elective craniotomy, whereas there were 43
      planned and 8 unplanned ICU admissions. The most common reasons for planned ICU
      admissions were anticipated lengthy operations (42%) and anesthetic risks (40%);
      causes for unplanned ICU admissions were mainly unexpected slow neurological
      recovery and extensive intraoperative blood loss. Of the 343 regular ward
      admissions, 10 (3%) required a MET call; only 3 of these MET calls occurred
      within the first 48 postoperative hours and did not lead to an ICU admission. The
      overall mortality rate in the investigated cohort was 1%, with no fatalities in
      patients admitted to the normal ward postoperatively. CONCLUSIONS: Routine ward
      admission for patients undergoing elective craniotomies with selective ICU
      admission appears safe; however, approximately 2% of patients may require a
      direct postoperative unplanned ICU admission. Patients with anticipated long
      operation times, extensive blood loss, and high anesthetic risks should be
      selected for postoperative ICU admission, but further study is needed to
      determine the preoperative factors that can aid in identifying and caring for
      these groups of patients.

PMID- 21888475
TI  - Mechanisms of vascular endothelial growth factor-induced pathfinding by
      endothelial sprouts in biomaterials.
AB  - A critical property of biomaterials for use in regenerative medicine applications
      is the ability to promote angiogenesis, the formation of new vascular networks,
      to support regenerating tissues. Recent studies have demonstrated that a complex
      interplay exists between biomechanical and biochemical regulators of endothelial
      cell sprouting, an early step in angiogenesis. Here, we use a microfluidic
      platform to study the pathfinding behaviors induced by various stable vascular
      endothelial growth factor (VEGF) gradients during sprouting morphogenesis within
      biomaterials. Quantitative, time-lapse analysis of endothelial sprouting
      demonstrated that the ability of VEGF to regulate sprout orientation during
      several stages of sprouting morphogenesis (initiation, elongation, and turning
      navigation) was biomaterial dependent. Identical VEGF gradients induced different
      types of coordinated cell movements depending on the density of the surrounding
      collagen/fibronectin matrix. In denser matrices, sprouts were more likely to have
      an initial orientation aligned parallel to the VEGF gradient. In contrast, in
      less dense matrices, sprouts were more likely to initially misalign with the VEGF
      gradient; however, these sprouts underwent significant turning and navigation to
      eventually reorient to be parallel to the VEGF gradient. These less dense
      matrices required shallower VEGF gradients and demonstrated lower activating VEGF
      thresholds to induce proper sprout alignment and pathfinding. These results
      encourage the future use of microfluidic platforms to probe fundamental aspects
      of matrix effects on angiogenesis, to screen biomaterials for angiogenic
      potential, and to design ex vivo tissues with aligned vascular networks.

PMID- 21888477
TI  - Postoperative outcomes following closed head injury and craniotomy for evacuation
      of hematoma in patients older than 80 years.
AB  - OBJECT: Advances in the management of trauma-induced intracranial hematomas and
      hemorrhage (epidural, subdural, and intraparenchymal hemorrhage) have improved
      survival in these conditions over the last several decades. However, there is a
      paucity of research investigating the relation between patient age and outcomes
      of surgical treatment for these conditions. In this study, the authors examined
      the relation between patient age over 80 years and postoperative outcomes
      following closed head injury and craniotomy for intracranial hemorrhage. METHODS:
      A consecutive population of patients undergoing emergent craniotomy for
      evacuation of intracranial hematoma following closed head trauma between 2006 and
      2009 was identified. Using multivariable logistic regression models, the authors
      assessed the relation between age (> 80 vs <= 80 years) and postoperative
      complications, intensive care unit stay, hospital stay, morbidity, and mortality.
      RESULTS: Of 103 patients, 27 were older than 80 years and 76 patients were 80
      years of age or younger. Older age was associated with longer length of hospital
      stay (p = 0.014), a higher rate of complications (OR 5.74, 95% CI 1.29-25.34),
      and a higher likelihood of requiring rehabilitation (OR 3.28, 95% CI 1.13-9.74).
      However, there were no statistically significant differences between the age
      groups in 30-day mortality or ability to recover to functional baseline status.
      CONCLUSIONS: The findings suggest that in comparison with younger patients,
      patients over 80 years of age may be similarly able to return to preinjury
      functional baselines but may require increased postoperative medical attention in
      the forms of rehabilitation and longer hospital stays. Prospective studies
      concerned with the relation between older age, perioperative parameters, and
      postoperative outcomes following craniotomy for intracranial hemorrhage are
      needed. Nonetheless, the findings of this study may allow for more informed
      decisions with respect to the care of elderly patients with intracranial
      hemorrhage.

PMID- 21888478
TI  - Just say NO to vasospasm.

PMID- 21888479
TI  - Reversal of cerebral vasospasm via intravenous sodium nitrite after subarachnoid
      hemorrhage in primates.
AB  - OBJECT: Subarachnoid hemorrhage (SAH)-induced vasospasm is a significant
      underlying cause of aneurysm rupture-related morbidity and death. While long-term
      intravenous infusion of sodium nitrite (NaNO(2)) can prevent cerebral vasospasm
      after SAH, it is not known if the intravenous administration of this compound can
      reverse established SAH-induced vasospasm. To determine if the intravenous
      infusion of NaNO(2) can reverse established vasospasm, the authors infused
      primates with the compound after SAH-induced vasospasm was established. METHODS:
      Subarachnoid hemorrhage-induced vasospasm was created in 14 cynomolgus macaques
      via subarachnoid implantation of a 5-ml blood clot. On Day 7 after clot
      implantation, animals were randomized to either control (saline infusion, 5
      monkeys) or treatment groups (intravenous NaNO(2) infusion at 300 MUg/kg/hr for 3
      hours [7 monkeys] or 8 hours [2 monkeys]). Arteriographic vessel diameter was
      blindly analyzed to determine the degree of vasospasm before, during, and after
      treatment. Nitric oxide metabolites (nitrite, nitrate, and S-nitrosothiols) were
      measured in whole blood and CSF. RESULTS: Moderate-to-severe vasospasm was
      present in all animals before treatment (control, 36.2% +/- 8.8% [mean +/- SD];
      treatment, 45.5% +/- 12.5%; p = 0.9). While saline infusion did not reduce
      vasospasm, NaNO(2) infusion significantly reduced the degree of vasospasm (26.9%
      +/- 7.6%; p = 0.008). Reversal of the vasospasm lasted more than 2 hours after
      cessation of the infusion and could be maintained with a prolonged infusion.
      Nitrite (peak value, 3.7 +/- 2.1 MUmol/L), nitrate (18.2 +/- 5.3 MUmol/L), and S
      nitrosothiols (33.4 +/- 11.4 nmol/L) increased significantly in whole blood, and
      nitrite increased significantly in CSF. CONCLUSIONS: These findings indicate that
      the intravenous infusion of NaNO(2) can reverse SAH-induced vasospasm in
      primates. Further, these findings indicate that a similar treatment paradigm
      could be useful in reversing cerebral vasospasm after aneurysmal SAH.

PMID- 21888480
TI  - Sudden death from diffuse leptomeningeal oligodendrogliomatosis.
AB  - In this paper the authors describe the rare disorder of diffuse leptomeningeal
      oligodendrogliomatosis in a patient with an oligodendroglioma of the cauda equina
      who died suddenly. Reviewing this uncommon pathological entity is important so
      that it can be recognized and treated appropriately. This young, otherwise
      healthy woman with initial symptoms of low-back pain had a mass lesion of the
      cauda equina. During a workup, profound refractory intracranial hypertension
      suddenly developed despite aggressive surgical and medical intervention. Autopsy
      revealed a spinal cord oligodendroglioma with diffuse leptomeningeal
      oligodendrogliomatosis of the brain and spinal cord. Given the unforeseen outcome
      in this patient, this entity, although rare, should be considered in patients
      with similar presentations and addressed early to prevent similar outcomes. A
      review of the details of this case as well as the literature is presented below.

PMID- 21888481
TI  - Morbidity and mortality after spinal deformity surgery in patients 75 years and
      older: complications and predictive factors.
AB  - OBJECT: As the population continues to age, relatively older geriatric patients
      will present more frequently with complex spinal deformities that may require
      surgical intervention. To the authors' knowledge, no study has analyzed factors
      predictive of complications after major spinal deformity surgery in the very
      elderly (75 years and older). The authors' objective was to determine the rate of
      minor and major complications and predictive factors in patients 75 years of age
      and older who underwent major spinal deformity surgery requiring a minimum 5
      level arthrodesis procedure. METHODS: Twenty-one patients who were 75 years of
      age or older and underwent thoracic and/or lumbar fixation and arthrodesis across
      5 or more levels for spinal deformity were analyzed retrospectively. The medical
      and surgical records were reviewed in detail. Age, diagnosis, comorbidities,
      operative data, hospital data, major and minor complications, and deaths were
      recorded. Factors predictive of perioperative complications were identified by
      logistic regression analysis. RESULTS: The mean patient age was 77 years old
      (range 75-83 years). There were 14 women and 7 men. The mean follow-up was 41.2
      months (range 24-81 months). Fifteen patients (71%) had at least 1 comorbidity. A
      mean of 10.5 levels were fused (range 5-15 levels). Thirteen patients (62%) had
      at least 1 perioperative complication, and 8 (38%) had at least one major
      complication for a total of 17 complications. There were no perioperative deaths.
      Increasing age was predictive of any perioperative complication (p = 0.03).
      However, major complications were not predicted by age or comorbidities as a
      whole. In a subset analysis of comorbidities, only hypertension was predictive of
      a major complication (OR 10, 95% CI 1.3-78; p = 0.02). Long-term postoperative
      complications occurred in 11 patients (52%), and revision fusion surgery was
      necessary in 3 (14%). CONCLUSIONS: Patients 75 years and older undergoing major
      spinal deformity surgery have an overall perioperative complication rate of 62%,
      with older age increasing the likelihood of a complication, and a long-term
      postoperative complication rate of 52%. Patients in this age group with a history
      of hypertension are 10 times more likely to incur a major perioperative
      complication. However, the mortality risk for these patients is not increased.

PMID- 21888485
TI  - Can we explain why some people do and some people do not act on their intentions?
AB  - Behavioural theorists have identified attitudes, perceived norms and self
      efficacy as the important determinants of people's intentions to engage in a
      given behaviour. Because intentions predict behaviour, these same variables also
      account for a considerable amount of the variation in behaviour. Nevertheless,
      there is often a substantial proportion of the population who do not act on their
      intentions. While a recently proposed integrative theory of behaviour suggests
      that these 'failures' are due either to a lack of skills and/or to the presence
      of environmental constraints, it has also been argued that the determinants of
      intention may have a direct, as well as in indirect, effect on behaviour. This
      paper uses data from a longitudinal study (Project RESPECT) to explore the extent
      to which attitudes, perceived norms and self-efficacy explain why some people do
      and others do not act on their intentions to engage in a health protective
      behaviour. Although the data provide further evidence that these three variables
      account for a significant proportion of the variance in intentions (and
      behaviour), they perform poorly when predicting behaviour for persons with pre
      existing high intentions. It may be reasonable to ask whether a 'new' theory is
      needed to explain why some people do, and some people do not, act on their
      intentions.

PMID- 21888486
TI  - Living with an incomplete vagina and womb: an interpretative phenomenological
      analysis of the experience of vaginal agenesis.
AB  - The objective of this study was to explore women's personal experiences of living
      with vaginal agenesis to gain insight in to psychological, social and emotional
      consequences of diagnosis and treatment. It employed interpretative
      phenomenological analysis for an in-depth exploratory study of a small sample of
      women with vaginal agenesis. The verbatim transcripts of semi-structured
      interviews with seven women diagnosed with vaginal agenesis were used as data for
      an interpretative phenomenological analysis. Four themes emerged which are
      described under the following headings: dealing with loss, the experience of
      medical services, sharing with others, and the role of time. Participants
      struggled to understand the meaning of their diagnosis and to incorporate it in
      to a new sense of self. Contact with medical services generally enhanced feelings
      of uncertainty and isolation. Emotional distress was managed through cognitive
      strategies and choices about disclosure to others. Participants described how the
      experience of their loss recurred over time in different ways depending on the
      salience of their sexual and reproductive identities. Some implications for
      health care professionals are discussed.

PMID- 21888482
TI  - A pilot study of poly(N-isopropylacrylamide)-g-polyethylene glycol and poly(N
      isopropylacrylamide)-g-methylcellulose branched copolymers as injectable
      scaffolds for local delivery of neurotrophins and cellular transplants into the
      injured spinal cord.
AB  - OBJECT: The authors investigated the feasibility of using injectable hydrogels,
      based on poly(N-isopropylacrylamide) (PNIPAAm), lightly cross-linked with
      polyethylene glycol (PEG) or methylcellulose (MC), to serve as injectable
      scaffolds for local delivery of neurotrophins and cellular transplants into the
      injured spinal cord. The primary aims of this work were to assess the
      biocompatibility of the scaffolds by evaluating graft cell survival and the host
      tissue immune response. The scaffolds were also evaluated for their ability to
      promote axonal growth through the action of released brain-derived neurotrophic
      factor (BDNF). METHODS: The in vivo performance of PNIPAAm-g-PEG and PNIPAAm-g-MC
      was evaluated using a rodent model of spinal cord injury (SCI). The hydrogels
      were injected as viscous liquids into the injury site and formed space-filling
      hydrogels. The host immune response and biocompatibility of the scaffolds were
      evaluated at 2 weeks by histological and fluorescent immunohistochemical
      analysis. Commercially available matrices were used as a control and examined for
      comparison. RESULTS: Experiments showed that the scaffolds did not contribute to
      an injury-related inflammatory response. PNIPAAm-g-PEG was also shown to be an
      effective vehicle for delivery of cellular transplants and supported graft
      survival. Additionally, PNIPAAm-g-PEG and PNIPAAm-g-MC are permissive to axonal
      growth and can serve as injectable scaffolds for local delivery of BDNF.
      CONCLUSIONS: Based on the results, the authors suggest that these copolymers are
      feasible injectable scaffolds for cell grafting into the injured spinal cord and
      for delivery of therapeutic factors.

PMID- 21888487
TI  - Lung function, adherence and denial in asthma patients who exhibit a repressive
      coping style.
AB  - Lung function, adherence and denial were explored in asthma patients who possess
      a repressive coping style (repressors). Repressors (low trait anxiety, high
      defensiveness) and non-repressors were identified by their trait anxiety and
      defensiveness scores. Participants completed measures of self-reported adherence,
      denial, morbidity and demographic data. A lung function measure (FEV(1)) was
      obtained for a subset of patients. Repressors, who comprised 33% of the sample,
      had significantly worse lung function but scored significantly higher on self
      reported adherence, compared to non-repressors. Age was positively correlated
      with adherence. Although repressive coping was positively correlated with denial,
      denial was significantly correlated with defensiveness but not trait anxiety. The
      study provides evidence that repressors are an important group to identify in
      future studies of asthma.

PMID- 21888488
TI  - Family caregivers and indicators of cancer-related distress.
AB  - Increases in the cost of medical care coupled with shorter hospital stays and an
      aging population are but a few of the reasons why home care for patients has
      become so important. This study examines variables that contribute to distress
      among lay-caregivers who provide home care to cancer survivors. Participants
      consisted of 135 survivor-caregiver dyads in which the caregiver was a member of
      the survivor's family or a close friend. Measures of caregiver distress were
      selected from the Ferrell et al. (1995) quality of life tool; predictor variables
      included cancer survivor and caregiver demographics, physical and emotional
      health status and behavioural characteristics. Hierarchical regression analysis
      indicated that, jointly, the three sets of indicators accounted for 35% of
      caregiver distress. Standardized regression coefficients indicated that
      relational deprivation (feelings of loss of togetherness, planned activities and
      contact with other individuals) was the most important predictor of caregiver
      distress (p<0.01). Female sex, less practice of healthy behaviours, greater
      number of patient care needs and pessimistic expectations (all ps<0.05) also were
      significant predictors in the final trimmed model. Results suggest that cancer
      support services that address the needs of the care receiver with the protection
      of the family caregiver in mind should be considered.

PMID- 21888489
TI  - Modelling the theory of planned behaviour and past behaviour.
AB  - This paper demonstrated two modelling techniques and three interpretations for
      the inclusion of past behaviour in a theory of planned behaviour (TPB) framework
      using structural equation modelling. Model 1 examined past behaviour as either a
      causal influence or as an autoregressive influence on current behaviour. Model 2
      demonstrated a novel approach to including past behaviour and current behaviour
      while preserving the tenets of the TPB, as it freed the residual correlation
      between past and present behaviour but not the causal path. Participants were 305
      undergraduate students (mean age = 19.42 years) who completed measures of the
      TPB, past exercise behaviour and current exercise behaviour at one-month follow
      up. Results demonstrated the importance of a priori conceptualization of past
      behaviour, as the models provide differences between estimated coefficients.
      Subsequent interpretation and decision to use each modelling strategy depends on
      the research objective and theory.

PMID- 21888490
TI  - Why do people self-harm?
AB  - The accuracy of perceptions about self-harm that are presented in the
      psychological and psychiatric literature was assessed with a sample of self
      harmers. A list of 20 statements containing ten myths and ten accurate statements
      about self-harm behaviour was incorporated into an internet-based questionnaire.
      Respondents (n = 243) rated their extent of agreement with each statement. Factor
      analysis confirmed the a priori classification of statements as being accurate.
      Only one item, regarding the relationship of self-harm to previous sexual abuse,
      did not confirm a priori classification; this statement was considered by self
      harmers to be an accurate perception of self-harm. It was concluded that this
      questionnaire could be a useful aid for group-work training with professionals
      who are involved in working with people who engage in self-harm.

PMID- 21888491
TI  - Illness representation of arterial hypertension in a sample of health
      professionals and the general public.
AB  - This work studies the illness representation of high blood pressure in a sample
      of primary health care professionals and the general public in order to identify
      possible differences. The examination of illness representation was carried out
      using a Spanish adaptation of Turk et al.'s ( 1986 ) Implicit Model of Illness
      Questionnaire. This questionnaire assesses nine components: identity, cause,
      incapacity, cure, personal responsibility, controllability, changeability and
      chance. The results showed statistically significant differences between the
      general public and doctors in all the components except controllability. Results
      also show that nurses' responses are closer to those of the general public in the
      social and psychological aspects, but not in the technical knowledge of
      hypertension.

PMID- 21888492
TI  - A psychometric evaluation of the Hospital Anxiety and Depression Scale during
      pregnancy.
AB  - The utility of the Hospital Anxiety and Depression Scale (HADS) as a screening
      instrument for anxiety and depression during pregnancy was investigated. A
      maximum likelihood factor analysis was conducted on the HADS to determine its
      psychometric properties and utility in 100 women from two culturally diverse
      populations (UK and Uzbekistan) at 12-weeks and 34-weeks pregnancy. The findings
      suggest that the HADS lacks the internal reliability requirements of a clinical
      assessment tool in this population. There was little evidence found to suggest
      that the HADS measures two dimensions of anxiety and depression consistently and
      reliably. The findings from this study suggest that the HADS could not be
      recommended as a clinical screening tool for anxiety and depression in pregnant
      women. Further research in this area is both desirable and required.

PMID- 21888493
TI  - Are coping resources related to humoral reaction induced by academic stress? An
      analysis of specific salivary antibodies to Epstein-Barr virus and
      cytomegalovirus.
AB  - The aim of the present study was to investigate whether coping resources mediated
      the changes in Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) specific
      salivary antibodies caused by academic stress. Fifty-four first-year female
      students of nursing and physiotherapy completed pencil and paper written
      questionnaires and concurrently donated saliva samples. The instrument included
      the short version of the Sense of Coherence (SOC) scale, measures of social
      support, current health, health practices, the scale of psychological distress,
      and state anxiety questionnaire. Data and saliva samples were collected one month
      after the beginning of the first semester, during term examinations period and a
      month into the second semester. Statistically significant changes in the level of
      specific salivary EBV and HCMV antibodies were observed between the four study
      points. State anxiety and psychological distress were significantly associated
      with HCMV-specific salivary antibody level increase during examinations and its
      decrease after the stress was over. Coping resources, however, were not
      associated with changes in any of the antibodies studied.

PMID- 21888494
TI  - A clinical guide to sleep disorders in children and adolescents.

PMID- 21888495
TI  - Ocular surface frostbite secondary to ethyl chloride spray.
AB  - CONTEXT: Ethyl chloride (EC) is a fast-acting vapo-coolant spray that provides
      rapid, transient, local analgesia for minor invasive procedures. Although the
      application of EC has decreased, it can be used as a cryoanalgesic agent in minor
      surgical procedures. OBJECTIVE: Despite the widespread use of EC as a local
      anesthetic, there are few reported cases of serious adverse side effects.
      MATERIAL AND METHODS: We report a 67-year old otherwise healthy man who underwent
      excision of a papilloma on his superior right eyelid by a general practitioner at
      a primary care center. The lesion was removed by curettage after slight freezing
      with EC spray. This chemical agent was applied without the adequate eye
      protection, and eight hours later the patient presented an acute frost injury of
      ocular surface. RESULTS: Urgent treatment included copious irrigation of the
      affected eye, especially the conjunctival fornices, corticosteroid (prednisone)
      and antibiotic (neomycin) ointment. A week later, the eyelid lesion and
      keratoconjunctivitis had resolved but evidence of early cicatrization involving
      the inferior conjucntival fornix and symblepharon formation were present.
      DISCUSSION: To the best of our knowledge, this is the first reported case of an
      acute burn of the ocular surface following EC spray exposure. CONCLUSION: EC
      should be avoided for short-term local anesthesia in the periocular region to
      prevent this serious complication.

PMID- 21888496
TI  - Generalized pustular eruptions due to terbinafine.
AB  - Terbinafine, a widely used antifungal agent, may rarely cause cutaneous side
      effects with an incidence of 2.7%. Generalized pustular eruptions are quite
      uncommon but severe adverse cutaneous reactions of terbinafine have been
      reported. The main pustular eruptions due to terbinafine include acute
      generalized exanthematous pustulosis and drug induced pustular psoriasis. In this
      report, two cases of acute generalized exanthematous pustulosis and one case of
      generalized pustular psoriasis triggered with terbinafine are presented.

PMID- 21888497
TI  - Reconciling ethical and legal aspects in neonatal intensive care.
AB  - During the last two decades there has been an enormous development in treatment
      possibilities for the extremely premature infants and the Neonatologists have to
      face in their daily practice many decisional problems and ethical, moral and
      legal dilemmas. These concern decisions to initiate or withhold treatment
      directly at birth, decision to withdrawn treatment with the possible consequence
      that the child will die. The debate between "sanctity" and "quality" of life,
      aggressive treatment in relation to discrimination toward the disabled, the
      principle of "beneficence" and the question of "proportionality" of treatment,
      the concept of the newborn's "best interest" are the ethical issues discussed.
      According to our opinion, ethical questions should not be regulated by law and
      the legal system should not interfere in the relationship patient - physician.
      Today more than ever, every neonatologist needs to become familiar with basic
      ethical concepts and the legal aspects in neonatal intensive care.

PMID- 21888498
TI  - Predicting American Indian adolescent substance use trajectories following
      inpatient treatment.
AB  - This study examined the effects of psychopathological, peer, family, and cultural
      predictors of American Indian adolescents' drug use following inpatient
      treatment. Data regarding lifetime, 90 days prior to treatment, and 1-year
      posttreatment substance use were collected using interviews, questionnaires, and
      observations of 57 American Indian adolescents and their families. Trajectories
      of days-used measures were subjected to semiparametric trajectory analysis.
      Trajectories were then compared on baseline measures by using both univariate and
      multivariate logit regression techniques. The study sought to identify prerelease
      predictors of membership in post-inpatient treatment substance use trajectory
      groups. Findings provide insight into the unique and shared risk and protective
      factors relevant to American Indian adolescents' substance use outcomes. In
      particular, this study suggests that a combination of family management and
      American Indian traditional cultural practices in families serves as a potential
      target for interventions to reduce substance use in adolescence.

PMID- 21888499
TI  - Cultural accommodation of substance abuse treatment for Latino adolescents.
AB  - Collaboration with community stakeholders is an often suggested step when
      integrating cultural variables into psychological treatments for members of
      ethnic minority groups. However, there is a dearth of literature describing how
      to accomplish this process within the context of substance abuse treatment
      studies. This article describes a qualitative study conducted through a series of
      focus groups with stakeholders in the Latino community. Data from focus groups
      were used by the researchers to guide the integration of cultural variables into
      an empirically supported substance abuse treatment for Latino adolescents
      currently being evaluated for efficacy. A model for culturally accommodating
      empirically supported treatments for ethnic minority participants is also
      described.

PMID- 21888501
TI  - Beliefs and perceived norms concerning smoking cessation program recruitment
      among African American teen smokers: what appeals to youth and what turns them
      away.
AB  - A qualitative approach was used to investigate the beliefs and perceived norms
      about participation in smoking cessation programs among a sample of African
      American alternative school students (N = 53), aged 14 to 18 years old, in the
      United States who were current smokers. The authors found that the majority of
      participants felt that smoking cessation programs were not effective, caused
      smoking, or lacked activities. Both boys and girls believed that communication
      sources that provided direct messages in real situations were the best motivators
      or incentives for African American youth recruitment into smoking cessation
      programs. These findings support research that African Americans are more
      attentive to communications that involve direct personal stimuli. In addition,
      African Americans place heavy emphasis on source and message style to determine
      credibility of the intervention strategy.

PMID- 21888500
TI  - Racial disparities in substance abuse treatment and the ecological fallacy.
AB  - This study examined engagement in treatment in substance abuse treatment programs
      that treated primarily either African American or White clients. Findings showed
      higher levels of engagement in White programs; however, engagement of African
      Americans in White programs was similar to that of Whites and was greater than
      Whites in African American programs. No significant differences emerged when a
      mixed model analysis considered additional variables of staff consensus
      (regarding treatment elements), treatment climate, acceptance of Medicaid
      clients, the proportion mandated to treatment, and the quality of the physical
      space. Although African American programs may show poorer levels of engagement
      than White programs, attribution of engagement in treatment to client level
      race/ethnicity should be made with caution.

PMID- 21888502
TI  - 'Heads held high': an exploratory study of legal highs in pre-legislation
      Ireland.
AB  - The research aimed to present a unique 'snapshot' of legal psychoactive drug use
      prior to legislative control in Ireland, in relation to the types of products
      used; sourcings; consumptive practices and particular social settings for use;
      gauging of dosage; licit and illicit drug transitions, individualisation of drug
      decision-making and experiences; and future intentions regarding drug switching
      post legislation. Semi-structured in depth interviews (n = 32) were conducted
      with adults aged 18-33 years who had used legal highs in the 6 months prior to
      fieldwork. The findings indicate some support for 'differentiated' displacement
      consumptive patterns between illegal and legal drugs, with user pathways grounded
      in 'legal high' availability; perceived user effect, safety, legality, quality
      and price. Mephedrone emerged as most popular drug of choice. Internet sales,
      stockpiling and diversion of previously 'legal highs' onto the illegal street
      drug market remain of concern, against a background of emerging new designer
      drugs in Ireland.

PMID- 21888503
TI  - Are health journalists' practices tied to their perceptions of audience? An
      attribution and expectancy-value approach.
AB  - This study examines a national survey of U.S. health journalists (N = 774) to
      ascertain how journalists' perceptions of audience use of health news shapes
      their journalistic practices. We establish a framework through attribution theory
      and expectancy-value theory for how journalists choose to fulfill their roles as
      providers of health information. Using these theoretical lenses, we look at
      whether health journalists' audience orientation is associated with their use of
      accessibility-oriented or credibility-focused practices. Our findings show that,
      overall, journalists believe readers are individually responsible for their
      health outcomes and that journalists focus on providing accessibility-oriented
      information when they feel their audience's ability to understand information may
      be compromised. Journalists' beliefs about audience behavior are associated with
      their attitudes toward communication practices.

PMID- 21888504
TI  - Inhibitory effect of antioxidant extracts from various potatoes on the
      proliferation of human colon and liver cancer cells.
AB  - Antioxidant extracts from 5 potato lines were evaluated for antioxidant activity,
      total phenolics, chlorogenic acid, anthocyanin content, and in vitro anticancer
      capacity. Analysis showed that Mexican wild species S. pinnatisectum had the
      highest antioxidant activity, total phenolic, and chlorogenic acid content. The
      proliferation of colon cancer and liver cancer cells was significantly inhibited
      by potato antioxidant extracts. The highest antiproliferative activity was
      observed in extracts of S. pinnatisectum and the lowest in Northstar. An inverse
      correlation was found between total phenolics and the EC(50) of colon cancer cell
      (R(2)  = 0.9303), as well as liver cancer cell proliferation (R(2)  = 0.8992).
      The relationship between antioxidant activity and EC(50) of colon cancer/liver
      cancer cell proliferation was significant (R(2)  = 0.8144; R(2)  = 0.956,
      respectively). A significant difference in inhibition of cancer cells (P < 0.01)
      existed between the 3 polyphenols: chlorogenic acid, pelargonidin chloride, and
      malvidin chloride, suggesting that chlorogenic acid was a critical factor in the
      antiproliferation of colon cancer and liver cancer cells.

PMID- 21888506
TI  - Inhibitory effect of vitamin C in combination with vitamin K3 on tumor growth and
      metastasis of Lewis lung carcinoma xenografted in C57BL/6 mice.
AB  - Vitamin C in combination with vitamin K3 (vit CK3) has been shown to inhibit
      tumor growth and lung metastasis in vivo, but the mechanism of action is poorly
      understood. Herein, C57BL/6 mice were implanted (s.c.) with Lewis lung carcinoma
      (LLC) for 9 days before injection (i.p.) with low-dose (100 mg vit C/kg + 1 mg
      vit K3/kg), high-dose (1,000 mg vit C/kg + 10 mg vit K3/kg) vit CK3 twice a week
      for an additional 28 days. As expected, vit CK3 or cisplatin (6 mg/kg, as a
      positive control) significantly and dose-dependently inhibited tumor growth and
      lung metastasis in LLC-bearing mice. Vit CK3 restored the body weight of tumor
      bearing mice to the level of tumor-free mice. Vit CK3 significantly decreased
      activities of plasma metalloproteinase (MMP)-2, -9, and urokinase plasminogen
      activator (uPA). In lung tissues, vit CK3 1) increased protein expression of
      tissue inhibitor of metalloproteinase-1 (TIMP-1), TIMP-2, nonmetastatic protein
      23 homolog 1 and plasminogen activator inhibitor-1; 2) reduced protein expression
      of MMP-2 and MMP-9; and 3) inhibited the proliferating cell nuclear antigen
      (PCNA). These results demonstrate that vit CK3 inhibits primary tumor growth and
      exhibits antimetastastic potential in vivo through attenuated tumor invasion and
      proliferation.

PMID- 21888505
TI  - Ganoderma lucidum (Reishi) inhibits cancer cell growth and expression of key
      molecules in inflammatory breast cancer.
AB  - Inflammatory breast cancer (IBC) is the most lethal and least understood form of
      advanced breast cancer. Its lethality originates from its nature of invading the
      lymphatic system and absence of a palpable tumor mass. Different from other
      metastatic breast cancer cells, IBC cells invade by forming tumor spheroids that
      retain E-cadherin-based cell-cell adhesions. Herein we describe the potential of
      the medicinal mushroom Ganoderma lucidum (Reishi) as an attractive candidate for
      anti-IBC therapy. Reishi contains biological compounds that are cytotoxic against
      cancer cells. We report the effects of Reishi on viability, apoptosis, invasion,
      and its mechanism of action in IBC cells (SUM-149). Results show that Reishi
      selectively inhibits cancer cell viability although it does not affect the
      viability of noncancerous mammary epithelial cells. Apoptosis induction is
      consistent with decreased cell viability. Reishi inhibits cell invasion and
      disrupts the cell spheroids that are characteristic of the IBC invasive
      pathology. Reishi decreases the expression of genes involved in cancer cell
      survival and proliferation (BCL-2, TERT, PDGFB), and invasion and metastasis (MMP
      9), whereas it increases the expression of IL8. Reishi reduces BCL-2, BCL-XL, E
      cadherin, eIF4G, p120-catenin, and c-Myc protein expression and gelatinase
      activity. These findings suggest that Reishi is an effective anti-IBC
      therapeutic.

PMID- 21888507
TI  - A conversation with Elwood Jensen. Interview by David D. Moore.

PMID- 21888510
TI  - Small for gestational age preterm infants: nutritional strategies and quality of
      growth after discharge.
AB  - Infants born preterm are at high risk for poor growth achievement. Small for
      gestational age (SGA (birth weight below the 10th percentile) preterm infants are
      even more prone to develop postnatal growth retardation in the early neonatal
      period, as they do not have a large storage of protein/energy. Both SGA and
      appropriate for gestational age (AGA: birth weight between the 10th and 90th
      percentiles) infants show persistent postnatal growth failure after discharge.
      Although the available data clearly demonstrate that preterm infants, especially
      if born SGA, exhibit postnatal growth retardation at the time of hospital
      discharge, the importance of the nutritional post discharge management has not
      been sufficiently taken into account. We have recently conducted a randomized
      controlled trial to assess whether infants born SGA may benefit from an enriched
      post discharge formula. This study suggests that the growth pattern in SGA
      preterm infants is not affected by the consumption of an enriched post discharge
      formula. The ponderal and linear growth of these infants does not accelerate to
      achieve early catch up growth. However, as far as the quality of growth is
      concerned, the fat mass accretion after term decelerates, so that an increase of
      fat free mass accretion takes place. Future research effort should be directed
      toward longer follow up and personalized nutrition management.

PMID- 21888508
TI  - Nuclear sphingolipid metabolism.
AB  - Nuclear lipid metabolism is implicated in various processes, including
      transcription, splicing, and DNA repair. Sphingolipids play roles in numerous
      cellular functions, and an emerging body of literature has identified roles for
      these lipid mediators in distinct nuclear processes. Different sphingolipid
      species are localized in various subnuclear domains, including chromatin, the
      nuclear matrix, and the nuclear envelope, where sphingolipids exert specific
      regulatory and structural functions. Sphingomyelin, the most abundant nuclear
      sphingolipid, plays both structural and regulatory roles in chromatin assembly
      and dynamics in addition to being an integral component of the nuclear matrix.
      Sphingosine-1-phosphate modulates histone acetylation, sphingosine is a ligand
      for steroidogenic factor 1, and nuclear accumulation of ceramide has been
      implicated in apoptosis. Finally, nuclear membrane-associated ganglioside GM1
      plays a pivotal role in Ca(2+) homeostasis. This review highlights research on
      the factors that control nuclear sphingolipid metabolism and summarizes the roles
      of these lipids in various nuclear processes.

PMID- 21888511
TI  - Direct-to-consumer genetic testing: perceptions, problems, and policy responses.
AB  - Direct-to-consumer (DTC) genetic testing has attracted a great amount of
      attention from policy makers, the scientific community, professional groups, and
      the media. Although it is unclear what the public demand is for these services,
      there does appear to be public interest in personal genetic risk information. As
      a result, many commentators have raised a variety of social, ethical, and
      regulatory issues associated with this emerging industry, including privacy
      issues, ensuring that DTC companies provide accurate information about the risks
      and limitations of their services, the possible adverse impact of DTC genetic
      testing on healthcare systems, and concern about how individuals may interpret
      and react to genetic risk information.

PMID- 21888512
TI  - Recent progress in HIV-associated nephropathy.
AB  - The classic kidney disease of HIV infection, HIV-associated nephropathy (HIVAN),
      is an aggressive form of collapsing focal segmental glomerulosclerosis with
      accompanying tubular and interstitial lesions. HIVAN was first described among
      African-Americans and Haitian immigrants with advanced HIV disease, an early
      suggestion of a strong genetic association. This genetic susceptibility was
      recently linked to polymorphisms on chromosome 22 in individuals of African
      descent. The association with advanced HIV infection and evidence from HIV
      transgenic mice suggested the possibility that HIV directly infects the kidney
      and that specific HIV gene expression induces host cellular pathways that are
      responsible for HIVAN pathogenesis. Although combination antiretroviral therapy
      has substantially reduced the impact of HIVAN in the United States, continued
      growth of the HIV epidemic in susceptible African populations may have important
      public health implications. This article reviews recent progress in the
      pathogenesis and treatment of HIVAN and describes the changing epidemiology of
      HIV-related kidney disease.

PMID- 21888509
TI  - A new look at electrolyte transport in the distal tubule.
AB  - The distal nephron plays a critical role in the renal control of homeostasis.
      Until very recently most studies focused on the control of Na(+), K(+), and water
      balance by principal cells of the collecting duct and the regulation of solute
      and water by hormones from the renin-angiotensin-aldosterone system and by
      antidiuretic hormone. However, recent studies have revealed the unexpected
      importance of renal intercalated cells, a subtype of cells present in the
      connecting tubule and collecting ducts. Such cells were thought initially to be
      involved exclusively in acid-base regulation. However, it is clear now that
      intercalated cells absorb NaCl and K(+) and hence may participate in the
      regulation of blood pressure and potassium balance. The second paradigm
      challenging concept we highlight is the emerging importance of local paracrine
      factors that play a critical role in the renal control of water and electrolyte
      balance.

PMID- 21888513
TI  - Relationships between medicine and industry: approaches to the problem of
      conflicts of interest.
AB  - Relationships between physicians and industry are prevalent in medical education,
      clinical practice, and research, as well as at the level of medical institutions.
      These relationships can be valuable for the advancement of medicine but have also
      received increased scrutiny in recent years because they create conflicts of
      interest that pose a risk of biasing the judgments of physicians. Responses to
      these conflicts of interest by medical institutions, journals, and governments
      have utilized four main tools: education, disclosure, management, and
      prohibition. Each of the four has its advantages and drawbacks. Medicine faces
      the challenge of tailoring the use of these tools to minimize the risk of bias
      while allowing useful medical-industry collaborations to proceed. Viewing the
      dilemmas created by physicians' relationships with industry as a version of the
      principal-agent problem, which is much discussed by economists, may help in
      developing creative approaches to these issues.

PMID- 21888514
TI  - Physician workforce projections in an era of health care reform.
AB  - In 2020, the United States may face shortages of 45,400 primary care physicians
      and 46,100 medical specialists-a total of 91,500 too few doctors. Unfortunately,
      health workforce shortages like these are being advanced as cause for repealing
      or "defunding" the Affordable Care Act (ACA). The extension of health insurance
      coverage to millions of Americans is a critical first step toward a healthier
      America. It would be a national failure to leave millions of Americans without
      health insurance coverage because they will generate additional demand. Rather,
      the solution is to find ways to meet that demand. Workforce projections utilizing
      real data and carefully formulated assumptions to assess how and why supply and
      demand change over time can greatly assist policy makers in finding those
      solutions. With implementation of the ACA under way, it is time to understand
      what lessons such projections can teach, and to begin to heed those lessons.

PMID- 21888515
TI  - Multiple sclerosis: new insights in pathogenesis and novel therapeutics.
AB  - Concepts of multiple sclerosis (MS) have shifted from the traditional view of a T
      cell-mediated, demyelinating disease of the white matter to include a broad range
      of immunopathogenic mechanisms, axonal damage, and widespread gray matter
      pathology. The cause of MS remains unknown, but recent epidemiological work has
      focused on genetic factors; environmental factors such as vitamin D, sunlight,
      and Epstein-Barr virus; and the controversial theory of chronic cerebrospinal
      venous insufficiency. Revised criteria facilitate making the diagnosis of MS.
      Emerging therapies are rapidly expanding treatment options, including both
      parenterally administered and oral medications. Strategies to preserve tissue,
      promote repair, and restore function are under development, and it is anticipated
      that they will provide better options for patients with progressive disease.

PMID- 21888516
TI  - Nanoparticle delivery of cancer drugs.
AB  - Nanomedicine, the application of nanotechnology to medicine, enabled the
      development of nanoparticle therapeutic carriers. These drug carriers are
      passively targeted to tumors through the enhanced permeability and retention
      effect, so they are ideally suited for the delivery of chemotherapeutics in
      cancer treatment. Indeed, advances in nanomedicine have rapidly translated into
      clinical practice. To date, there are five clinically approved nanoparticle
      chemotherapeutics for cancer and many more under clinical investigation. In this
      review, we discuss the various nanoparticle drug delivery platforms and the
      important concepts involved in nanoparticle drug delivery. We also review the
      clinical data on the approved nanoparticle therapeutics as well as the
      nanotherapeutics under clinical investigation.

PMID- 21888517
TI  - Sound strategies: the 65-million-year-old battle between bats and insects.
AB  - The intimate details regarding the coevolution of bats and moths have been
      elucidated over the past 50 years. The bat-moth story began with the evolution of
      bat sonar, an exquisite ultrasonic system for tracking prey through the night
      sky. Moths countered with ears tuned to the high frequencies of bat echolocation
      and with evasive action through directed turns, loops, spirals, drops, and power
      dives. Some bat species responded by moving the frequency and intensity of their
      echolocation cries away from the peak sensitivity of moth ears, and the arms race
      was on. Tiger moths countered by producing anti-bat sounds. Do the sounds
      advertise moth toxicity, similar to the bright coloration of butterflies; do they
      startle the bat, giving the moth a momentary advantage in their aerobatic battle;
      or do they jam the sonar of the bat? The answer is yes. They do all and more in
      different situations and in different species. Any insect that flies at night
      must deal with bat predation. Beetles, mantids, true crickets, mole crickets,
      katydids, green lacewings, and locusts have anti-bat strategies, and we have just
      scratched the surface. In an exciting new twist, researchers are taking the
      technologies developed in the laboratory back into the field, where they are
      poised to appreciate the full richness of this remarkable predator-prey
      interaction.

PMID- 21888518
TI  - Insect responses to major landscape-level disturbance.
AB  - Disturbances are abrupt events that dramatically alter habitat conditions and
      resource distribution for populations and communities. Terrestrial landscapes are
      subject to various disturbance events that create a matrix of patches with
      different histories of disturbance and recovery. Species tolerances to extreme
      conditions during disturbance or to altered habitat or resource conditions
      following disturbances determine responses to disturbance. Intolerant populations
      may become locally extinct, whereas other species respond positively to the
      creation of new habitat or resource conditions. Local extinction represents a
      challenge for conservation biologists. On the other hand, outbreaks of
      herbivorous species often are triggered by abundant or stressed hosts and
      relaxation of predation following disturbances. These insect responses can cause
      further changes in ecosystem conditions and predispose communities to future
      disturbances. Improved understanding of insect responses to disturbance will
      improve prediction of population and community dynamics, as well as ecosystem and
      global changes.

PMID- 21888519
TI  - Approaches and incentives to implement integrated pest management that addresses
      regional and environmental issues.
AB  - Agricultural, environmental, and social and policy interests have influenced
      integrated pest management (IPM) from its inception. The first 50 years of IPM
      paid special attention to field-based management and market-driven decision
      making. Concurrently, IPM strategies became available that were best applied both
      within and beyond the bounds of individual fields and that also provided
      environmental benefits. This generated an incentives dilemma for farmers:
      selecting IPM activities for individual fields on the basis of market-based
      economics versus selecting IPM activities best applied regionally that have
      longer-term benefits, including environmental benefits, that accrue to the
      broader community as well as the farmer. Over the past several decades, public
      supported incentives, such as financial incentives available to farmers from
      conservation programs for farms, have begun to be employed to encourage use of
      conservation techniques, including strategies with IPM relevance. Combining
      private investments with public support may effectively address the incentives
      dilemma when advanced IPM strategies are used regionally and provide public goods
      such as those benefiting resource conservation. This review focuses on adaptation
      of IPM to these broader issues, on transitions of IPM from primarily individual
      field-based decision making to coordinated community decision making, and on the
      form of partnerships needed to gain long-lasting regional and environmental
      benefits.

PMID- 21888520
TI  - Transmission of flea-borne zoonotic agents.
AB  - Flea-borne zoonoses such as plague (Yersinia pestis) and murine typhus
      (Rickettsia typhi) caused significant numbers of human cases in the past and
      remain a public health concern. Other flea-borne human pathogens have emerged
      recently (e.g., Bartonella henselae, Rickettsia felis), and their mechanisms of
      transmission and impact on human health are not fully understood. Our review
      focuses on the ecology and epidemiology of the flea-borne bacterial zoonoses
      mentioned above with an emphasis on recent advancements in our understanding of
      how these organisms are transmitted by fleas, maintained in zoonotic cycles, and
      transmitted to humans. Emphasis is given to plague because of the considerable
      number of studies generated during the first decade of the twenty-first century
      that arose, in part, because of renewed interest in potential agents of
      bioterrorism, including Y. pestis.

PMID- 21888521
TI  - Group size and its effects on collective organization.
AB  - Many insects and arthropods live in colonies or aggregations of varying size.
      Group size may affect collective organization either because the same individual
      behavior has different consequences when displayed in a larger group or because
      larger groups are subject to different constraints and selection pressures than
      smaller groups. In eusocial colonies, group size may have similar effects on
      colony traits as body size has on organismal traits. Social insects may,
      therefore, be useful to test theories about general principles of scaling, as
      they constitute a distinct level of organization. However, there is a surprising
      lack of data on group sizes in social insects and other group-living arthropods,
      and multiple confounding factors have to be controlled to detect effects of group
      size. If such rigorous studies are performed, group size may become as important
      to understanding collective organization as is body size in explaining behavior
      and life history of individual organisms.

PMID- 21888522
TI  - Unexpected effect of recruitment procedure on lung volume measured by respiratory
      inductive plethysmography (RIP) during high frequency oscillatory ventilation
      (HFOV) in preterm neonates with respiratory distress syndrome (RDS).
AB  - BACKGROUND: In clinical practice, one of the major problems in optimizing
      recruitment or lung volume during HFOV in preterm infants is the inability to
      accurately measure direct changes in lung volume at bedside. OBJECTIVE: To
      evaluate changes in lung volume during the recruitment phase of elective HFOV in
      preterm infants with RDS using respiratory inductive plethysmography. MATERIAL
      AND METHODS: The preliminary results of an observational prospective study were
      reported. Newborns with GA <= 27 weeks requiring elective HFOV for a diagnosis of
      RDS were studied within the first 6 hours of life using RIP technology, before
      surfactant instillation. HFOV was performed with Draeger Babylog 8000 plus
      ventilator with "optimum lung volume strategy "(continuous distending pressure
      (CDP) increased step-by-step until FiO(2) <= 0.25 was reached). Data on
      ventilator settings, gas exchange and RIP volume were collected and analyzed. The
      analysis package used in this study visualizes measured data from the Bicore-II
      device (CareFusion), Pulse Oximeter Masimo, AX300 FiO(2) monitor device and TCM4
      shuttle (TCM4, Radiometer, Copenaghen, Denmark). RESULTS: Four preterm infants
      (two females) with mean +/- SD gestational age of 26.5 +/- 1.0 weeks and mean +/-
      SD birth weight of 978 +/- 188 grams were studied. Relative FRC slightly
      increased during the first steps of the recruitment phase, while deeply decreased
      at higher CDP values (>= 15 cm H(2)O). Notwithstanding FiO(2) decreased until
      0.25 in all the newborns except one. CONCLUSIONS: Because RIP cannot
      differentiate between changes in lung fluid or intrathoracic gas, we hypothesized
      that as CDP increases and total lung capacity is approached, pulmonary vascular
      resistance increases as a consequence of the compression of intra-alveolar
      vessels. This increases right ventricular afterload which, combined with re
      establishment of right-to left shunting, results in decreased pulmonary blood
      flow and then decreased lung volume. Caution should then be used when using high
      CDP values during the recruitment procedure.

PMID- 21888523
TI  - The appropriateness of early discharge of very low birth weight newborns.
AB  - Preterm newborns may be discharged when clinical conditions are stable and
      maturity of physiological functions has been gained, but no precise indications
      on weight and GA to be reached before discharge are available. In our NICU we
      have observed in the last five years 234 newborns < 32 weeks of GA; we have
      decided to transfer from incubators at the mean weight of 1737 g, regardless of
      their GA and birth weight and to discharge at a mean weight of 1966 g, the lowest
      mean weight in comparison to the other twelve NICUs of the Lazio region. We have
      analyzed if the major diseases affecting those newborns (RDS, mechanical
      ventilation, PDA, IVH/PVL, PHH, NEC, ROP, sepsis ) have influenced weight at
      discharge in 13 NICUs of Lazio region. CONCLUSIONS: in our NICU the discharge of
      ELBW/VLBW preterm newborns < 32 weeks GA and/or < 1500 g can be feasible at a
      mean weight close to 1900 g. An early transfer from incubator at a mean weight of
      1737 g promotes an early discharge from hospital. Major diseases affecting those
      newborn haven't influenced weight at discharge.

PMID- 21888524
TI  - The fractions of respiratory tract cells at risk in formaldehyde carcinogenesis.
AB  - Clonal growth modeling of carcinogenesis requires data on the number of cells at
      risk of becoming cancerous. We synthesized literature data to estimate the
      fraction of respiratory tract epithelial cells that are progenitor cells, and
      therefore at risk, in formaldehyde carcinogenesis for specific respiratory tract
      regions. We concluded that the progenitor cells for the transitional and
      respiratory epithelia of the nose are basal and nonciliated cells and Type II
      cells in the alveolar region. In the conducting airways, our evaluation indicated
      that ciliated and basal cells are not in the progenitor pool. Respiratory tract
      epithelial cell fractions of 0.819 in rats and 0.668 in humans were estimated
      from the data. The total numbers of epithelial cells in the lower respiratory
      tract of humans and rats were allocated to individual generations. Cell cycle
      times were also estimated from literature data, since the reciprocal of cell
      cycle time is an important variable in clonal growth modeling. Sensitivity
      analyses of a previously published risk model for formaldehyde carcinogenesis
      showed that specification of the fraction of cells at risk markedly affects
      estimates of some parameters of the clonal growth model. When all epithelial
      cells are considered part of the progenitor pool, additional risks for the non
      smoking population was typically over predicted by about 35% for high exposure
      levels. These results demonstrate the importance of accurately identifying cell
      populations at risk when applying quantitative models in risk assessments.

PMID- 21888525
TI  - Endotoxin-induced coagulation reactions and phenoloxidase activity modulation in
      Sudanonautes africanus hemolymph fractions.
AB  - Sudanonautes africanus is a freshwater crab local to Nigeria and West Africa that
      has no documentation of its innate immunity reactions. The objective of this
      study was to assess the effect of endotoxin (lipopolysaccharide [LPS]) on
      coagulation and on phenoloxidase (PO) activity in the hemolymph fractions of S.
      africanus. The hemolymph from each of 10 live crabs was obtained by carapace
      puncture and then fractionated into plasma and hemocytes. The hemocytes were then
      processed and then fractionated into hemocyte lysate (HL), hemocyte lysate
      supernatant (HLS), and hemocyte lysate debris (HLD). In one study, each fraction
      was then incubated with a fixed level of LPS in the presence or absence of
      exogenous calcium (Ca(2+)) ion. In another study, the LPS concentration was
      varied in order to study its effect on protein coagulation when an optimal ratio
      mixture of plasma:HLS was present as well as on PO activity in the plasma and HLS
      fractions. The results of the first set of studies demonstrated that a presence
      of Ca(2+) in the LPS-induced clotting reactions was essential. The next set of
      studies showed that a 7:1 plasma:HLS mixture yielded a higher level of
      coagulation than any other ratio tested in the presence of 1 EU LPS/ml. When this
      same plasma:HLS mixture ratio was used to ascertain the effect of varying LPS
      level on coagulation, the response trended higher up to a dose of 3.0 EU/ml., and
      decreased thereafter until 7 EU/ml. As expected based on the effect of LPS on PO
      activation, an increasing presence of LPS led to a general trend increase in
      activity of the enzyme in the plasma fraction; however, the effect was moreover
      inhibitory in the HLS fraction. From the results here, we conclude that protein
      coagulation is an important response, along with increased PO activity, that
      could manifest in Sudanonautes africanus after exposure to 'free' LPS or select
      LPS-bearing organisms in their environment.

PMID- 21888526
TI  - Neuroimaging examination of newborns in vertically acquired infections.
AB  - Congenital/perinatal nervous system (CNS) infections are an important cause of
      mortality and morbidity in neonatal period, and long-term sequelae. Many
      pathogens can lead to infections frequently involving the CNS, with possible
      disruption of brain development, which often is related to gestational age of
      maternal infection. The mechanism of infection and damage is different among the
      infectious agents, leading to more specific pathologic findings. It is necessary
      in newborns with confirmed or suspected CNS infection to undergo investigation by
      neuroimaging techniques to help healthcare providers, give adequate treatment and
      follow-up care and counsel parents. Computed tomography, Magnetic Resonance
      Imaging and cerebral ultrasonography are fundamental tools in evaluating infants
      with suspected or proved congenital/perinatal infections. Each imaging technique
      has its advantages, disadvantages and limits, since they are sometimes
      complementary.

PMID- 21888527
TI  - Forearm muscle size, strength, force, and power in relation to pQCT-derived bone
      strength at the radius in adults.
AB  - We aimed to examine the relationship between forearm muscle cross-sectional area
      (MCSA), muscle force, or rate of torque development (RTD) and 2 estimated radius
      bone strength indices - compressive bone strength index (BSI) at the wrist and
      strength strain index in torsion (SSI(p)) at the shaft - in healthy middle-aged
      males and females. Distal (4%) and shaft (65%) sites of nondominant forearms were
      scanned using peripheral quantitative computed tomography (pQCT) in a sample of
      48 adults (mean age +/- SD, 49.4 +/- 2.4 y) to obtain estimated bone strength
      indices and MCSA. Muscle force, measured by grip dynamometry and wrist flexion
      RTD, was obtained using an isokinetic dynamometer. Hierarchical linear
      regressions, adjusted for weight, explained 27% and 36% of the BSI variance at
      the 4% site in males and premenopausal females, respectively (p < 0.05). At the
      radius shaft, weight explained 26% (p < 0.05) and 83% (p < 0.01) of SSI(p)
      variance. The unique variance of BSI explained by MCSA was 16% in males (p <
      0.05) and 31% in females (p < 0.01). Grip force predicted variance in SSI(p) in
      males (p < 0.01) and BSI in females (p < 0.05). RTD did not explain any variance
      in BSI or SSI(p). Body weight was the only significant predictor (p < 0.05) of
      SSI(p) in females. Although forearm muscle size and grip strength are associated
      with estimates of radius bone strength at midlife, this relationship appears to
      be sex dependent. The differences observed between muscle size and strength
      properties and bone strength at distal and shaft sites of the radius suggest a
      property-, sex-, and site-specific relationship between muscle and bone in the
      forearm.

PMID- 21888528
TI  - Skeletal muscle and beyond: the role of exercise as a mediator of systemic
      mitochondrial biogenesis.
AB  - It has been known for more than 4 decades that exercise causes increases in
      skeletal muscle mitochondrial enzyme content and activity (i.e., mitochondrial
      biogenesis). Increasing evidence now suggests that exercise can induce
      mitochondrial biogenesis in a wide range of tissues not normally associated with
      the metabolic demands of exercise. Perturbations in mitochondrial content and
      (or) function have been linked to a wide variety of diseases, in multiple
      tissues, and exercise may serve as a potent approach by which to prevent and (or)
      treat these pathologies. In this context, the purpose of this review is to
      highlight the effects of exercise, and the underlying mechanisms therein, on the
      induction of mitochondrial biogenesis in skeletal muscle, adipose tissue, liver,
      brain, and kidney.

PMID- 21888529
TI  - Deacetylation of PGC-1alpha by SIRT1: importance for skeletal muscle function and
      exercise-induced mitochondrial biogenesis.
AB  - Activation of peroxisome proliferator-activated receptor gamma coactivator-1alpha
      (PGC-1alpha)-mediated transcription is important for both the determination of
      mitochondrial content and the induction of mitochondrial biogenesis in skeletal
      muscle. SIRT1 (silent mating type information regulator 2 homolog 1)
      deactetylation is proposed as a potential activator of PGC-1alpha transcriptional
      activity. The current review examines the importance of SIRT1 deacetylation of
      PGC-1alpha in skeletal muscle. Models of SIRT1 overexpression and pharmacological
      activation are examined, but changes in SIRT1 expression and deacetylase activity
      following acute and chronic contractile activity will be emphasized. In addition,
      potential mechanisms of SIRT1 activation in skeletal muscle will be examined. The
      importance of the PGC-1alpha acetyltransferase GCN5 will also be briefly
      discussed. The current evidence supports the contribution of SIRT1 deacetylation
      of PGC-1alpha to exercise-induced mitochondrial biogenesis. Further research
      examining exercise-mediated activation of SIRT1 and the role of GCN5 in
      regulating PGC-1alpha transcriptional activity in skeletal muscle  is required.

PMID- 21888530
TI  - Reduction of heart sound interference from lung sound signals using empirical
      mode decomposition technique.
AB  - During the recording time of lung sound (LS) signals from the chest wall of a
      subject, there is always heart sound (HS) signal interfering with it. This
      obscures the features of lung sound signals and creates confusion on pathological
      states, if any, of the lungs. A novel method based on empirical mode
      decomposition (EMD) technique is proposed in this paper for reducing the
      undesired heart sound interference from the desired lung sound signals. In this,
      the mixed signal is split into several components. Some of these components
      contain larger proportions of interfering signals like heart sound, environmental
      noise etc. and are filtered out. Experiments have been conducted on simulated and
      real-time recorded mixed signals of heart sound and lung sound. The proposed
      method is found to be superior in terms of time domain, frequency domain, and
      time-frequency domain representations and also in listening test performed by
      pulmonologist.

PMID- 21888531
TI  - Biomarkers of fruit and vegetable intake in human intervention studies: a
      systematic review.
AB  - Observational evidence consistently shows that consumption of a diet rich in
      fruit and vegetables may offer protection against diseases such as cardiovascular
      disease and cancer. Assessment of dietary intake is complex and prone to many
      sources of error. More objective biomarkers of fruit and vegetable intake are
      therefore of interest. The aim of this review is to examine the usefulness of the
      main biomarkers of fruit and vegetable intake to act as objective indicators of
      compliance in dietary intervention studies. A comprehensive search of the
      literature was conducted using six databases. Suitable papers were selected and
      relevant data extracted. The papers were categorized into 3 sub-groups: whole
      diet interventions; mixed fruit and vegetable interventions; and studies
      involving individual varieties of fruits or vegetables. Ninety-six studies were
      included in the review. Overall, the most commonly measured, and most
      consistently responsive, biomarkers were the carotenoids and vitamin C. Based on
      the results of this systematic review, it remains prudent to measure a panel of
      biomarkers in fruit and vegetable intervention studies. The only possible
      exception to this is "fruit only" intervention studies where assessment of
      vitamin C alone may suffice.

PMID- 21888532
TI  - A review on rice bran protein: its properties and extraction methods.
AB  - Rice bran protein has been found to be of high quality and of importance for food
      and pharmaceutical applications. It is a plant protein that can be derived from
      rice bran, an abundant and cheap agricultural byproduct. The protein content in
      rice bran is about 10-15% and it consists of 37% water-soluble, 31% salt-soluble,
      2% alcohol-soluble, and 27% alkali-soluble storage proteins. Its unique property
      as being hypoallergenic and having anti-cancer activity makes it a superior
      cereal protein that may find a wide range of applications. There were already
      reports on the extraction of rice bran protein several decades ago. However, as
      of now, commercial rice bran protein is still unavailable in the market. This
      review is aimed at providing valuable discussions on rice bran protein, that is,
      storage protein, its various properties, and extraction methods for the
      development of an effective processing scheme. Also, an update on the current
      processing methods is also included.

PMID- 21888533
TI  - Does protein supplementation prevent muscle disuse atrophy and loss of strength?
AB  - Recently there has been much interest in the use of dietary amino acids
      supplements to decrease the losses in muscle mass and strength observed after
      space flight or during aging using bed rest analogs. This interest persists even
      if the results have been mixed. Of the six published amino acid supplementation
      studies, three showed benefit, three did not. A recent study re-evaluating
      protein requirements in humans suggests that the official RDA is 41%
      underestimated. Interestingly, the three studies that showed benefits fed their
      test subjects a baseline protein level around the old RDA for protein. The three
      that did not show benefit gave the subjects a baseline protein intake higher than
      the new RDA. We suggest that the positive effects observed on protein metabolism
      might just reflect the benefits of adequate protein intake achieved during bed
      rest rather than a protective effect against bed-rest induced disuse. In
      conclusion, the efficiency of amino acid countermeasures for preventing the loss
      in protein mass during space flight or bed rest needs to be seriously questioned.
      These results extend to clinical situations such as serious illness and progress
      of aging in which physical inactivity is a significant component of the loss in
      muscle function.

PMID- 21888534
TI  - Reaction kinetics in food extrusion: methods and results.
AB  - Extrusion cooking is a highly efficient food processing technology. During the
      extrusion process, there are many desirable and undesirable reactions which will
      determine final product quality. While being heated and sheared simultaneously,
      food raw materials experience a non-isothermal process and their residence time
      in the extruder is distributed. All these factors contribute to the difficulties
      in determining the kinetic parameters for those reactions. Therefore, this paper
      attempts to review the reaction kinetics in food extrusion. First of all, the
      kinetic models for the reactions are outlined. After elucidating how to determine
      reaction time in an extruder, the methodological approaches for determining the
      reaction order, rate constant, and activation energy of a reaction under
      isothermal or non-isothermal conditions with or without residence time
      distribution (RTD) are presented. Then, different models relating the rate
      constant to its various impact factors, with especially focusing on shear stress,
      are reviewed. Subsequently, how shear stress is estimated in an extruder, is
      illustrated. In the last part of this paper, the reported data of rate constant,
      reaction order, and activation energy for the reactions occurring during food
      extrusion are summarized, with detailed impacts of temperature, moisture content,
      shear stress, and determination method on these kinetic parameters. Finally,
      future research needs are suggested.

PMID- 21888535
TI  - Update on the relationship of fish intake with prostate, breast, and colorectal
      cancers.
AB  - A systematic review of prospective cohort and case-control studies investigating
      relationships between the intake of fish and incidence of prostate, breast, or
      colorectal cancers was conducted. A total of 106 studies fulfilled the
      requirements stated in the "Search strategy and selection criteria." Among 273
      estimates of association reported by these studies, 53 indicated decreased risk
      while 12 indicated increased risk associated with fish intake. The hypothesis
      linking fish consumption and low cancer incidence appears to be supported by
      little epidemiological data. However, there are several factors that may mask
      potential protective associations with fish intake. The type and the amount of
      fish eaten, the cooking method, the stage of the cancer and, amongst women,
      menopausal status may all be important factors that relate to whether fish is
      protective or not. Future epidemiologic studies with a clearer assessment of
      these factors are needed to know more about the effects of fish consumption on
      cancer risk. Therefore, until there are better measures of dietary exposure or
      biomarkers to correlate self-report, no conclusion can be drawn regarding the
      recommendation for increasing fish consumption in general to reduce the risk of
      developing the most common cancers in Western societies.

PMID- 21888536
TI  - Antimicrobial edible films and coatings for fresh and minimally processed fruits
      and vegetables: a review.
AB  - The use of edible films and coatings is an environmentally friendly technology
      that offers substantial advantages for shelf-life increase of many food products
      including fruits and vegetables. The development of new natural edible films and
      coatings with the addition of antimicrobial compounds to preserve fresh and
      minimally processed fruits and vegetables is a technological challenge for the
      industry and a very active research field worldwide. Antimicrobial agents have
      been successfully added to edible composite films and coatings based on
      polysaccharides or proteins such as starch, cellulose derivatives, chitosan,
      alginate, fruit puree, whey protein isolated, soy protein, egg albumen, wheat
      gluten, or sodium caseinate. This paper reviews the development of edible films
      and coatings with antimicrobial activity, typically through the incorporation of
      antimicrobial food additives as ingredients, the effect of these edible films on
      the control of target microorganisms, the influence of antimicrobial agents on
      mechanical and barrier properties of stand-alone edible films, and the effect of
      the application of antimicrobial edible coatings on the quality of fresh and
      fresh-cut fruits and vegetables.

PMID- 21888537
TI  - Midfacial soft tissue changes after leveling Le Fort I osteotomy with
      differential reduction. Cone-beam computed tomography volume superimposition.
AB  - OBJECTIVE: To compare the short- and long-side soft tissue changes in the
      midfacial areas of patients who have undergone superior repositioning Le Fort I
      osteotomies for the correction of occlusal cant. The null hypothesis was that
      there were no significant differences in the midfacial soft tissue changes
      between the greater- and lesser-reduction sides. MATERIALS AND METHODS: The
      subjects included 25 patients who had undergone Le Fort I osteotomy with superior
      repositioning and mandibular setback sagittal split ramus osteotomy. Using the
      cone-beam computed tomography volume superimposition method, the soft tissue
      changes were measured and determined both preoperatively and postoperatively. A
      10 * 27 grid at 4.5-mm (vertical) and 5-mm (horizontal) intervals was used for
      the hard to soft tissue response. RESULTS: The mean difference in the reduction
      from leveling Le Fort I osteotomy was 3.2 +/- 1.2 mm between the short and long
      sides (P < .05). The mandibular setback movement averaged 5.4 +/- 3.3 mm on the
      long side and 5.0 +/- 3.6 mm on the short side (P > .05). The soft tissue areas
      below the Frankfort horizontal (FH) plane to 13.5 mm showed different changes
      after the differential leveling Le Fort I osteotomies. CONCLUSIONS: The
      distinctly changed areas, which showed differences between the greater- and
      lesser-reduction sides beyond the 2.5-mm average for the soft tissue response,
      were below the FH plane to 13.5 mm and lateral to the midsagittal reference plane
      to 30 mm. In light of this, oral surgeons and orthodontists should be concerned
      about the volumetric midfacial difference after leveling the maxillary occlusal
      plane at the preoperative stage and thus should take appropriate measures to
      improve it.

PMID- 21888538
TI  - Dedication: professor Vladimir A. Efimov.

PMID- 21888539
TI  - Microcin C: biosynthesis, mode of action, and potential as a lead in antibiotics
      development.
AB  - The natural compound Microcin C (McC) is a Trojan horse inhibitor of aspartyl
      tRNA synthetases endowed with strong antibacterial properties, in which a
      heptapeptide moiety is responsible for active transport of the inhibitory
      metabolite part into the bacterial cell. The intracellularly formed aspartyl AMP
      analogue carries a chemically more stable phosphoramidate linkage, in comparison
      to the labile aspartyl-adenylate, and in addition is esterified with a 3
      aminopropyl moiety. Therefore, this compound can target aspartyl-tRNA synthetase.
      The biochemical production and secretion of McC, and the possibilities to develop
      new classes of antibiotics using the McC Trojan horse concept in combination with
      sulfamoylated adenosine analogues will be discussed briefly.

PMID- 21888540
TI  - Versatile solid supports for oligonucleotide synthesis that incorporate urea
      bridge.
AB  - The universal solid support, USIII, representing a new and improved version of
      commercial USII, as well as 2 '-deoxynucleoside and 2 '-deoxy-2 '
      fluoronucleoside bound supports, incorporating a labile phenoxyacetyl fragment,
      was synthesized by an aminomethyl polystyrene carbamoylation with corresponding
      azides in the presence of aqueous triethylammonium bicarbonate. All three solid
      phases incorporate a stable urea tether, thus bridging the polymer and functional
      linker. These new matrices proved to be potent solid phases for the synthesis of
      DNA, RNA, or modified oligonucleotides as well as randomized mixed 2 '-ribo/2 '
      deoxy-2 '-fluoro-RNA libraries and/or DNA libraries, randomized with
      trinucleotides (codons).

PMID- 21888541
TI  - Synthesis of biotin-containing phosphoramidite linker with polyether spacer arm.
AB  - A phosphoramidite linker unit, based on glycerol backbone and containing a biotin
      residue attached through a tetraethylene glycol spacer arm, was synthesized. DMTr
      Glycidol and tetraethylene glycol were used as starting materials. After
      conversion of one of hydroxy groups in tetraethylene glycol into an amino group,
      the epoxy cycle in DMTr-glycidol was opened by this amino alcohol, resulting in
      the corresponding ether and some quantity of secondary amine. After attaching of
      biotin residue to the ether followed by phosphitylation, the desirable linker was
      obtained. The structure of the linker was confirmed by (1)H-(1)H COSY, (1)H-(13)C
      HSQC, (1)H-(13)C HMBC, (1)H-(15)N HSQC, and (1)H-(15)N HMBC spectra. The resulted
      phosphoramidite linker unit is suitable for use in common DNA synthesizers. This
      approach can be used for preparation of various modifiers containing reporter
      groups attached to the primary amino function using conventional procedures.

PMID- 21888542
TI  - Facile synthesis of 8-azido-6-benzylaminopurine.
AB  - Bromination of 6-benzylaminopurine (1) with Br(2) in AcOH in the presence of
      AcONa afforded 6-benzylamino-8-bromopurine (2) in 59% yield. The position of
      bromination was confirmed by direct transformation of bromide 2 by reaction with
      NaN(3) in dimethyl sulfoxide to 8-azido-6-benzylaminopurine (3) in a yield of 70%
      and comparison of its properties with the known compound 2-azido-6
      benzylaminopurine (11). Compounds 3 and 11 were checked for their biological
      activity in specific biotests based on the primary cytokinin effects in living
      plants. Both synthesized compounds displayed effects similar to the typical
      cytokinin 6-benzylaminopurine (1).

PMID- 21888543
TI  - Synthesis of methylenebis(phosphonate) analogues of 2-, 4-, and 6-pyridones of
      nicotinamide adenine dinucleotide.
AB  - The synthesis of metabolically stable methylenebis(phosphonate) analogues of 2-,
      4-, and 6-pyridones of nicotinamide adenine dinucleotide (NAD) is reported. In
      contrast to natural pyrophosphates, these NAD analogues are able to penetrate the
      cell membrane and can be used as probes in cellular assays.

PMID- 21888544
TI  - Synthesis and properties of ApA analogues with shortened phosphonate
      internucleotide linkage.
AB  - A complete series of the 2 '-5 ' and 3 '-5 ' regioisomeric types of r(ApA) and 2
      '-d(ApA) analogues with the alpha-hydroxy-phosphonate C3 '-O-P-CH(OH)-C4 "
      internucleotide linkage, isopolar but non-isosteric with the phosphodiester one,
      were synthesized and their hybridization properties with polyU studied. Due to
      the chirality on the 5 '-carbon atom of the modified internucleotide linkage
      bearing phosphorus and hydroxy moieties, each regioisomeric type of ApA dimer is
      split into epimeric pairs. To examine the role of the 5 '-hydroxyl of the alpha
      hydroxy-phosphonate moiety during hybridization, the appropriate r(ApA) analogues
      with 3 '(2 ')-O-P-CH(2)-C4 " linkage lacking the 5 '-hydroxyl were synthesized.
      Nuclear magnetic resonance (NMR) spectroscopy study on the conformation of the
      modified sugar-phosphate backbone, along with the hybridization measurements,
      revealed remarkable differences in the stability of complexes with polyU,
      depending on the 5 '-carbon atom configuration. Potential usefulness of the alpha
      hydroxy-phosphonate linkage in modified oligoribonucleotides is discussed.

PMID- 21888545
TI  - Nucleotides part LXXX: Synthesis of 3'-O fluorescence labeled thymidine
      derivatives and their 5'-O-triphosphates.
AB  - A new labeling technique attaching a fluorescent pteridine derivative (3, 5) via
      a linker onto the 3'-OH group of 5'-O-dimethoxytritylthymidine (7) was developed
      to lead to the conjugates 8 and 11. After detritylation to give 9 and 12, the
      final conversion into the corresponding 5'-triphosphates (13, 14), which were
      isolated as sodium salts, was performed by known methods.

PMID- 21888547
TI  - Synthesis of oligoribonucleotides containing 2'-O-methoxymethyl group by the
      phosphotriester method.
AB  - An effective procedure for the synthesis of ribonucleotide monomers containing a
      2 '-O-methoxymethyl-modifying group was developed. These monomers were used for
      the synthesis of RNA fragments by the solid-phase phosphotriester method under O
      nucleophilic intramolecular catalysis. The properties of 2 '-O-methoxymethyl
      containing oligoribonucleotides were examined.

PMID- 21888546
TI  - 31P NMR and computational studies on stereochemistry of conversion of
      phosphoramidate diesters into the corresponding phosphotriesters.
AB  - 31P NMR spectroscopy was used to investigate a stereochemical course of a nitrite
      promoted conversion of phosphoramidate diesters into the corresponding
      phosphotriesters. It was found that this reaction occurred with almost complete
      epimerization at the phosphorus center and at the C1 atom in the amine moiety. On
      the basis of the 31P NMR data, a plausible mechanism for the reaction was
      proposed. The density functional theory calculation of the key step of the
      reaction, i.e., breaking of the P-N bond and formation of the P-O bond, suggested
      a one-step S(N)2(P) process with retention of configuration at the phosphorus
      center.

PMID- 21888548
TI  - DNA or RNA oligonucleotide 2'-hydrazides for chemoselective click-type ligation
      with carbonyl compounds.
AB  - An efficient method for the synthesis of DNA or RNA oligonucleotide 2'-hydrazides
      is described. Fully deprotected oligonucleotides containing a hydrazide group at
      the 2'-position of a uridine residue were obtained by a novel two-step procedure:
      periodate cleavage of an oligonucleotide with 1,2-diol group followed by
      conversion of the aldehyde to hydrazide with an extended linker arm using a
      homobifunctional reagent succinic dihydrazide and NaBH(3)CN. The resulting
      oligonucleotide 2'-hydrazides were efficiently conjugated by a click-type
      reaction at acidic pH to aliphatic or aromatic aldehydes with or without
      NaBH(3)CN reduction to afford novel 2'-conjugates.

PMID- 21888549
TI  - Postsynthetic modification of oligonucleotides with imidazophenazine dye and its
      effect on duplex stability.
AB  - Carboxyalkyl derivative of the intercalating agent imidazo[4,5-b]phenazine was
      used for the postsynthetic oligonucleotide modification. Model
      pentadecathymidylate-imidazophenazine conjugate was prepared from 5'-aminoalkyl
      modified (dT)(15) by using phosphonium coupling reagent BOP in the presence of 1
      hydroxybenzotriazole. Spectral-fluorescent properties of the conjugate were
      studied. The attachment of the dye was found to increase the thermal stability of
      (dT)(15) duplex with poly(dA) by more than 4 degrees C, probably by the
      intercalation mechanism.

PMID- 21888550
TI  - Polymerase-dependent DNA synthesis from phosphoramidate-activated nucleotides.
AB  - Nucleoside triphosphate mimetics, which are substrates for polymerases, can be
      used in the enzymatic synthesis of nucleic acids. Alternatively, they might also
      become reversible or irreversible enzyme inhibitors. In order to analyze the
      effects of 5'-phosphoramidate modification of deoxynucleotide in DNA synthesis, 3
      phosphono-L-Ala-dNMP (N = A, T, or G) were evaluated as substrates of HIV-1 RT,
      Vent (exo(-)), and Therminator polymerase, respectively. The DNA-dependent DNA
      polymerase activity is significantly higher for Vent exo(-) polymerase than for
      HIV-1 RT, which is reflected by the capacity of Vent exo(-) polymerase to
      efficiently synthesize DNA without stalling effects. In addition, Vent (exo(-))
      polymerase proved to be more accurate than Therminator polymerase, based on
      Watson-Crick base-pairing. The optimal yield (88%-97%) of full-length elongation
      can be obtained in 60 minutes by Vent (exo(-)) polymerase at 0.025 U/MUL, with
      the phosphoramidate analogues as substrates. These data led us to conclude that
      the optimal pyrophosphate mimetic for the enzyme-catalyzed synthesis of DNA is
      polymerase dependent.

PMID- 21888551
TI  - The Zn(2+) complex of 1,4,7,10-tetraazacyclododecane as an artificial nucleobase.
AB  - {2-Deoxy-3-O-[2-cyanoethoxy(diisopropylamino)phosphino]-5-O-(4,4'
      dimethoxytrityl)-alpha-D- erythro-pentofuranosyl}-N-{2-[4,7,10-tris(2,2,2
      trifluoroacetyl)-1,4,7,10-tetraazacyclododecan-1- yl]ethyl}acetamide (1) was
      prepared and incorporated into a 2'-O-methyl oligoribonucleotide. The
      hybridization of this oligonucleotide with complementary 2'-O-methyl
      oligoribonucleotides incorporating one to five uracil bases opposite to the
      azacrown structure was studied in the absence and presence of Zn(2+).
      Introduction of Zn(2+) moderately stabilized the duplex with U-bulged targets.

PMID- 21888552
TI  - Mechanism of CpG DNA methyltransferases M.SssI and Dnmt3a studied by DNA
      containing 2-aminopurine.
AB  - Murine DNA methyltransferases Dnmt3a-CD and M.SssI from Spiroplasma methylate
      cytosines at CpG sites. The role of 6-oxo groups of guanines in DNA methylation
      by these enzymes has been studied using DNA substrates, which contained 2
      aminopurine at different positions. Removal of the 6-oxo group of the guanine
      located adjacent to the target cytosine in the CpG site dramatically reduces the
      stability of the methyltransferase-DNA complexes and leads to a significant
      decrease in the methylation. Apparently, O6 of this guanine is involved in the
      recognition of CpG sites by the enzymes. Cooperative binding of Dnmt3a-CD to 2
      aminopurine-containing DNA and the formation of nonproductive enzyme-substrate
      complexes were observed.

PMID- 21888553
TI  - Crosslinking of (cytosine-5)-DNA methyltransferase SsoII and its complexes with
      specific DNA duplexes provides an insight into their structures.
AB  - (Cytosine-5)-DNA methyltransferase SsoII (M.SsoII) functions as a
      methyltransferase and also as a transcription factor. Chemical and photochemical
      crosslinking was used for exploring the structure of M.SsoII-DNA complexes and
      M.SsoII in the absence of DNA. Photocrosslinking with 4-(N-maleimido)benzophenone
      demonstrated that in the M.SsoII complex with DNA containing the regulatory site,
      the M.SsoII region responsible for methylation was bound to DNA flanking the
      regulatory site, which contained no methylation sequence. This required high
      flexibility of the linker connecting the M.SsoII N-terminal domain and the
      M.SsoII region responsible for methylation. The flexibility was demonstrated by
      crosslinking with bis-maleimidoethane and 1,11-bis-maleimidotetraethyleneglycol.

PMID- 21888554
TI  - Modulation of HIV-1 integrase activity by single-stranded oligonucleotides and
      their conjugates with eosin.
AB  - Integration of the DNA copy of the genomic RNA into an infected cell genome is
      one of the key steps of the replication cycle of all retroviruses. It is
      catalyzed by the viral enzyme, integrase. We have shown that conjugates of short
      single-stranded oligonucleotides with eosin efficiently inhibit the catalytic
      activity of the HIV-1 integrase. In this article, we have found that the
      dependence of the integrase catalytic activity on the concentration of
      oligonucleotides has a bell-shaped pattern. The modulation of HIV-1 integrase
      activity correlated with the oligonucleotide length and was not associated with
      specific sequences. Moreover, a similar mode of the oligonucleotide action was
      found for integrase from the prototype foamy virus. This dual effect of the
      oligonucleotide and their conjugates with eosin might be explained by their
      binding with retroviral integrase in two different sites; the
      oligodeoxynucleotide binding in the first site results in integrase activation,
      whereas interactions with another one lead to inhibition of the enzyme activity.
      Eosin coupling to oligonucleotides did not change the mode of their action but
      enhanced their affinity to both binding sites. The affinity increase was found to
      be much more important for the site responsible for the integrase inhibition,
      thus explaining the high inhibitory potency of oligonucleotide-eosin conjugates.

PMID- 21888555
TI  - Interaction of Escherichia coli RNA polymerase with artificial promoters,
      containing nonnucleotide spacers.
AB  - To study the functional role of the spacer region between two consensus -10 and 
      35 elements of promoters, recognized by E. coli RNA polymerase, the model
      promoter-like DNA duplexes containing nonnucleotide inserts (mimicking 17-mer
      spacer) either in one or both strands, were constructed. The modified duplexes
      can form the heparin-resistant binary complexes with RNA polymerase. The DNA
      duplex with nonnucleotide insert in the template strand can specifically direct
      the synthesis of mRNA in the in vitro run-off transcription assays.

PMID- 21888556
TI  - Entinostat for treatment of solid tumors and hematologic malignancies.
AB  - INTRODUCTION: A key feature of malignant cells is inappropriate gene suppression
      resulting in uncontrolled proliferation, continued cell cycling and a lack of
      differentiation. Histone deacetylase inhibitors (HDACi) are an emerging class of
      antineoplastic agents that counteract this effect and thus permit re-expression
      of silenced genes. Entinostat is an emerging HDACi that has shown promise in
      multiple preclinical studies. Additionally, Phase I and II clinical trials have
      begun to demonstrate its potential as a well-tolerated agent with anti-tumor
      activity. AREAS COVERED: The pharmacokinetics, pharmacodynamics, mechanisms of
      action, safety and tolerability, and clinical trials of entinostat are reviewed.
      Sources for this review included all relevant, publicly available, entinostat
      related peer-reviewed publications and meeting abstracts up to March 2011. EXPERT
      OPINION: Entinostat is a well-tolerated HDACi that demonstrates promising
      therapeutic potential in both solid and hematologic malignancies. Its efficacy
      does not appear directly dose-related, and as such, more relevant biomarkers are
      needed to adequately assess its activity. Future clinical trials will likely
      focus on its use in combination with other agents that are able to exploit the
      epigenetic changes rendered by deacetylase inhibition.

PMID- 21888557
TI  - A comparison of Malaysian and Australian speech-language pathologists' practices
      with children with developmental disabilities who are pre-symbolic.
AB  - The aim of this study was to explore the assessment, intervention, and family
      centred practices of Malaysian and Australian speech-language pathologists (SLPs)
      when working with children with developmental disabilities who are pre-symbolic.
      A questionnaire was developed for the study, which was completed by 65 SLPs from
      Malaysia and 157 SLPs from Australia. Data reduction techniques were used prior
      to comparison of responses across questionnaire items. Results indicated that
      SLPs relied mostly on informal assessments. Malaysian and Australian SLPs
      differed significantly in terms of obtaining information from outside the clinic
      to inform assessment. When providing intervention, SLPs focused mostly on
      improving children's pre-verbal skills. A third of Australian SLPs listed the
      introduction of some form of symbolic communication as an early intervention
      goal, compared to only a small percentage of Malaysian SLPs. Regarding family
      involvement, SLPs most often involved mothers, with fathers and siblings being
      involved to a lesser extent. Overall, it appeared that practices of Malaysian
      SLPs had been influenced by developments in research, although there were some
      areas of service delivery that continued to rely on traditional models. Factors
      leading to similarities and differences in practice of SLPs from both countries
      as well as clinical and research implications of the study are discussed.

PMID- 21888558
TI  - The effect of pause time upon the communicative interactions of young people who
      use augmentative and alternative communication.
AB  - This study investigated the effect of variation in partner-initiated pause time
      on the expressive communication of young people who use Augmentative and
      Alternative Communication (AAC). Eight participants aged 8;11-20;08 years (mean
      16;02 years) participated in the study. Three pause time conditions (2, 10, and
      45 seconds) were trialled during a scripted shared storybook reading task. A
      total of 27 turn opportunities were provided for participants during the task.
      Participant interactions were analysed for the percentage of responses made to a
      turn opportunity, mean length of utterance in words (MLU), percentage of
      assertive conversational acts made, and the modes of communication used. Findings
      indicated that participants were more likely to respond to a turn opportunity
      when their communication partner provided a longer pause time. Additionally, a
      longer pause time resulted in longer MLUs. Participants did not use more
      assertive conversational acts and continued to use a variety of communication
      modes when provided with a longer pause time. Results indicate that increasing
      pause time is an effective strategy to support the development of expressive
      communication for young people who use AAC. This suggests the need for
      professionals providing AAC services to encourage communication partners to
      provide extended pauses during interactions.

PMID- 21888559
TI  - Complex contextual influences on the communicative interactions of students with
      multiple and severe disabilities.
AB  - The aim of this study was to explore teachers' perceptions and experiences of
      supports and obstacles to engaging students with multiple and severe disabilities
      (MSD) in communicative interactions at school. Eleven teachers of students with
      MSD participated in two in-depth interviews. Interview transcripts were analysed
      for narrative structure and content themes. Inter-coder reliability for coding of
      content themes was 87.5%. Participants identified a broad range of factors,
      including: characteristics of individual students, attitudes, perceptions and
      beliefs of teachers and other staff, class structure, staffing, opportunities for
      collegiality, resources, funding, infrastructure, collaboration with speech
      language pathologists, appropriate communication education for teachers, the role
      of government departments, and broader societal factors. The findings suggest
      that there are complex contextual influences on the communicative interactions of
      students with MSD. While inadequate systemic supports appear to contribute to low
      frequencies of communication, systemic factors can be structured so that students
      participate in activities and have opportunities for communication. Further
      research is required with teachers of students with MSD to substantiate these
      findings.

PMID- 21888560
TI  - Gender specific associations of serum levels of brain-derived neurotrophic factor
      in anxiety.
AB  - OBJECTIVES: Whereas animal models indicate that brain-derived neurotrophic factor
      (BDNF) plays a role in anxiety-related behaviour, little is known about BDNF in
      patients with an anxiety disorder. We tested the hypothesis that serum BDNF
      levels are low in patients with an anxiety disorder as compared to healthy
      controls. We further examined the associations of gender and some of the clinical
      characteristics of anxiety with BDNF levels. METHODS: Serum BDNF levels were
      determined in 393 unmedicated, non-depressed patients with social anxiety
      disorder, panic disorder, agoraphobia, and generalised anxiety disorder (66.7%
      females) and in 382 healthy controls (62.0% females). RESULTS: Overall, there
      were no differences in BDNF levels among patients and controls, regardless of
      type of anxiety disorder. Analyses stratified by gender revealed that female
      patients had lower levels of BDNF relative to female controls (P < 0.05, d =
      0.19), which was stronger in female patients with > 1 anxiety disorder (P < 0.01,
      d = 0.32). BDNF levels were similar among male patients and controls and
      unrelated to the clinical characteristics of anxiety. CONCLUSION: Our results
      mirror preclinical findings indicating that gender plays a role in the
      association between BDNF and anxiety and suggest that BDNF might play a role in
      the pathophysiology of anxiety in women.

PMID- 21888561
TI  - A novel ascorbic acid-resistant nitroxide in fat emulsion is an efficient brain
      imaging probe for in vivo EPR imaging of mouse.
AB  - The loss of paramagnetism of nitroxide radicals due to reductant reactions in
      biological systems, places a fundamental time constraint on their application as
      an imaging probe in in vivo EPR imaging studies. However, in vitro studies of the
      newly synthesized tetraethyl-substituted piperidine nitroxide radical
      demonstrated high resistivity to paramagnetic reduction when exposed to ascorbic
      acid, a common reduction agent in biological systems. In this work we
      investigated the use of these nitroxides as an imaging probe in EPR imaging of
      small rodents. 2,2,6,6-Tetraethyl-piperidine nitroxide (TEEPONE) is not highly
      soluble in aqueous media, thus a lipid-based emulsion system of lecithin was used
      to solubilize TEEPONE. The obtained solution was homogenous and with low
      viscosity, allowing smooth intravenous injection into mice tail vein. Acquired
      three dimensional (3D) EPR images of mouse head clearly showed TEEPONE
      distributed in all tissues including brain tissues, with an average measurable
      signal half-life of more than 80 min, thus demonstrating high resistivity to
      reduction due to ascorbic acid in in vivo animal studies, and the potential for
      use of this compound in in vivo studies of animal model systems.

PMID- 21888562
TI  - Outbreak caused by Proteus mirabilis isolates producing weakly expressed TEM
      derived extended-spectrum beta-lactamase in spinal cord injury patients with
      recurrent bacteriuria.
AB  - We performed a retrospective extended-spectrum beta-lactamase (ESBL) molecular
      characterization of Proteus mirabilis isolates recovered from urine of spinal
      cord injury patients. A incorrectly detected TEM-24-producing clone and a new
      weakly expressed TEM-derived ESBL were discovered. In such patients, ESBL
      detection in daily practice should be improved by systematic use of a synergy
      test in strains of P. mirabilis resistant to penicillins.

PMID- 21888563
TI  - Fever of unknown origin: a retrospective study of 52 cases with evaluation of the
      diagnostic utility of FDG-PET/CT.
AB  - OBJECTIVES: Fever of unknown origin (FUO) is dynamic in its origin and will be an
      ongoing challenge to the clinician because of shifting disease epidemiology. Here
      we present a series of patients with classical FUO admitted to an infectious
      diseases department during a 5-y period, with an emphasis on the diagnostic
      utility of 18F-fluorodeoxyglucose positron emission tomography (PET)/computed
      tomography (CT) in present-day cases of FUO. METHODS: Patient records were
      reviewed retrospectively. RESULTS: A final diagnosis was achieved for 31 of the
      52 cases (60%). The final diagnoses of these 31 cases and their distribution in
      the respective diagnostic categories were: infections 32% (10/31), non-infectious
      inflammatory disease 55% (17/31), and malignancy 13% (4/31). In our study PET/CT
      successfully identified an infectious, inflammatory, or neoplastic cause of fever
      in 10 of the 22 patients (45%) who underwent this scan. CONCLUSIONS: During the
      past decade the proportion of non-infectious inflammatory diseases in FUO series
      has increased. Based on our findings we recommend: (1) a PET/CT scan be performed
      early in the diagnostic work-up of patients with FUO, and (2) restraint in
      performing invasive procedures in patients with FUO in whom no cause of fever has
      been determined during diagnostic work-up.

PMID- 21888564
TI  - Staphylococcus aureus in a northern Italian region: phenotypic and molecular
      characterization.
AB  - BACKGROUND: Staphylococcus aureus is a leading cause of community-acquired
      infections and healthcare-associated infections. Epidemiological data are useful
      for understanding the dynamics of the diffusion of this pathogen, and to plan
      control activities and monitor their efficacy. METHODS: S. aureus isolates were
      collected in 13 public hospital laboratories of Emilia-Romagna (northern Italy
      region) during February-March 2009; phenotypic and molecular characterizations of
      these isolates were performed. RESULTS: The study sample included 267 isolates,
      57 from blood, 81 from respiratory tract, and 129 from wounds; 106 (40%) were
      methicillin-resistant S. aureus (MRSA). MRSA showed a limited number of
      circulating clones with 2 predominant spa types--t008 and t041--accounting for
      36% and 27% of MRSA isolates, respectively. The t041 type had a higher prevalence
      of antimicrobial resistance compared to other spa types and accounted for most of
      the retrieved hetero-vancomycin-intermediate S. aureus (h-VISA), while t008 was
      more frequently detected in non-hospital isolates. A higher degree of genetic
      diversity was observed in methicillin-susceptible S. aureus (MSSA), with no
      predominant clones and low prevalence of antimicrobial resistance. The occurrence
      of community-acquired MRSA infection appears to be rare in Emilia-Romagna.
      CONCLUSIONS: In contrast to previous studies reporting Italian data, t008 was the
      most frequent spa type among MRSA isolates in Emilia-Romagna. The prevalence of
      antimicrobial resistance of different MRSA spa types could influence their
      ability to cause infections with hospital onset. The presence of only 2 major
      MRSA clones circulating in Emilia-Romagna increases the chances that a regional
      strategy aimed at MRSA prevention will be effective.

PMID- 21888565
TI  - Experiments on the mechanism of underwater hearing.
AB  - CONCLUSION: The findings suggest that underwater sound perception is realized by
      the middle ear rather than by bone conduction, at least in shallow water
      conditions. OBJECTIVE: To prove whether underwater sound perception is effected
      by bone conduction or by conduction via the middle ear. METHODS: Five divers,
      breathing through snorkels, were tested in a swimming pool, to determine whether
      a sound was louder when the acoustic source placed was in front of the head in
      comparison with a lateral application facing the ear region. The second
      experiment investigated whether sound perception is influenced by ear protection
      plugs in underwater conditions. Also, the effect of a 5 mm thick neoprene hood
      was determined, with and without an additional perforation in the ear region.
      RESULTS: Sounds were louder when applied from a position laterally facing the
      ear, louder without than with a protection plug, louder without than with a
      neoprene hood on, and louder when the neoprene hood had a perforation in the
      region of the ear than with an intact hood.

PMID- 21888566
TI  - The first report of bilateral retropharyngeal lymph node metastasis from
      papillary thyroid carcinoma and review of the literature.
AB  - The sites of lymph node metastasis of papillary thyroid carcinomas are typically
      the paratracheal and jugular lymph nodes. On the other hand, metastasis to the
      retropharyngeal or parapharyngeal nodes from papillary thyroid carcinomas is very
      rare. During the last two decades, limited to cases with a histologically
      definite diagnosis by surgery, only 39 cases have been reported. All reported
      cases were unilateral retropharyngeal or parapharyngeal node metastasis except
      one metachronous bilateral case, and there were no reports of simultaneous
      bilateral cases within our literature review. We report three cases of
      retropharyngeal node metastasis from thyroid papillary carcinoma, including a
      case of bilateral nodal metastasis. Retropharyngeal node metastasis was
      successfully resected in all three patients by the transcervical approach. As
      pointed out in past reports, this report also suggests that prior neck dissection
      and/or metastasis to cervical lymph nodes might alter the direction of lymphatic
      drainage to the retrograde fashion, resulting in the unusual metastasis to the
      retropharyngeal lymph nodes, and there is a possibility of a bilateral pattern.
      Also, it is necessary to consider the possibility of metastasis from a papillary
      thyroid carcinoma in the differential diagnosis of lymph node swelling in the
      parapharyngeal space.

PMID- 21888567
TI  - Risk factors for mortality in patients with Burkholderia cepacia complex
      bacteraemia.
AB  - BACKGROUND: Over the last 2 decades, Burkholderia cepacia complex has emerged as
      a serious human pathogen, especially in critically ill patients. B. cepacia
      complex has been associated with increased morbidity and mortality in intensive
      care unit patients. However, in our literature search, we could not find studies
      on risk factors for mortality in patients with B. cepacia complex bacteraemia.
      Therefore, we investigated risk factors for mortality in B. cepacia complex
      bacteraemia. METHODS: Clinical characteristics and laboratory parameters of 27
      patients with 1 or more blood cultures positive for B. cepacia complex from
      January 2006 to October 2010 in Severance Hospital, Yonsei University College of
      Medicine, Korea were retrospectively analyzed. The main outcome measure was
      overall 28-day mortality. Appropriate initial empirical antimicrobial use was
      defined as administration of agent(s) to which the organism was susceptible
      within 24 h of obtaining blood for culture. RESULTS: The overall 28-day mortality
      rate was 41% (11/27). In univariate analysis, underlying diabetes mellitus (p =
      0.033), inappropriate initial empirical antimicrobial therapy (p = 0.033), and an
      elevated Sequential Organ Failure Assessment (SOFA) score (p = 0.002) were
      significantly associated with mortality. In multivariate analysis, inappropriate
      initial empirical antimicrobial therapy and an elevated SOFA score were
      independent risk factors for increased mortality (p = 0.032 and p = 0.028,
      respectively). CONCLUSIONS: An elevated SOFA score and inappropriate initial
      empirical antimicrobial therapy were significantly associated with adverse
      outcome in patients with B. cepacia complex bacteraemia.

PMID- 21888568
TI  - Methyl-aminolevulinate photodynamic therapy for the treatment of erythroplasia of
      Queyrat in 23 patients.
AB  - Erythroplasia of Queyrat (EQ) is an intraepithelial squamous cell carcinoma
      localized on the mucosal or transitional surfaces. Standard therapy usually
      consists of the surgical removal of the cancer. The use of non-invasive
      alternative procedures, such as photodynamic therapy (PDT), has been considered
      for the treatment of EQ, although only a few reports regarding isolated cases or
      small series exist. We describe our cumulative experience with PDT, using topical
      methyl-aminolevulinate (MAL), for the management of 23 male patients with EQ of
      the glans penis and/or prepuce. Patients underwent two consecutive weekly MAL-PDT
      sessions, with the second session postponed in seven patients because of an
      excessive local reaction. Nineteen patients obtained a complete clinical
      remission without any sign of recurrence over an average post-treatment period of
      18 months (range, 8-30 months). Cosmetic outcome was excellent in most patients,
      while dyschromic changes occurred in four cases. All patients experienced
      transient local adverse reactions and 22 of them reported severe or very severe
      symptoms during the session.

PMID- 21888569
TI  - The role of tumor necrosis factor-alpha and other cytokines in depression: what
      dermatologists should know.
AB  - Recent studies have suggested that inflammatory responses may play an important
      role in the pathophysiology of depression. In fact, depressed individuals have
      been found to have higher levels of pro-inflammatory cytokines, especially tumor
      necrosis factor-alpha (TNF-alpha) and interleukin-6. This appears to be
      independent of any pre-existing chronic inflammatory disorders. In this article,
      various studies correlating increased levels of cytokines to depression are
      reviewed. As much as 60% of individuals with psoriasis also suffer from clinical
      depression. TNF-alpha antagonists, frequently used in the treatment of psoriasis,
      may be helpful in directly reducing depressive symptoms for patients with
      psoriasis and other chronic inflammatory conditions.

PMID- 21888570
TI  - Abobotulinum toxin A and onabotulinum toxin A for masseteric hypertrophy: a split
      face study in 25 Korean patients.
AB  - Masseter muscle hypertrophy has been treated for cosmetic purposes using several
      modalities, including injection of type A or type B botulinum toxin into the
      masseter muscle. In this report, we compared the efficacy and safety of
      abobotulinum toxin A with onabotulinum toxin A treatment for masseteric
      hypertrophy in 25 Korean patients with a conversion factor of 2.5:1 through a
      controlled, split-face, and evaluator-blinded study. The mean grade of clinical
      improvement based on clinical assessment was 2.8 +/- 0.9 for abobotulinum toxin A
      and 2.7 +/- 0.8 for onabotulinum toxin A at 8 weeks after the injection. At 12
      weeks after the injection, the mean grade of clinical improvement based on
      clinical assessment was 2.9 +/- 0.9 for abobotulinum toxin A and 2.7 +/- 0.8 for
      onabotulinum toxin A. More pronounced improvement was observed with abobotulinum
      toxin A than onabotulinum toxin A in three (12%) patients at 8 weeks and five
      (20%) patients at 12 weeks. We believe that our data can be used as an essential
      reference for determining the dose of type A botulinum toxin in the treatment of
      masseteric hypertrophy.

PMID- 21888571
TI  - The P-element-induced silencing effect of KP transposons is dose dependent in
      Drosophila melanogaster.
AB  - Transposable elements are found in the genomes of all eukaryotes and play a
      critical role in altering gene expression and genome organization. In Drosophila
      melanogaster, transposable P elements are responsible for the phenomenon of
      hybrid dysgenesis. KP elements, a deletion-derivative of the complete P element,
      can suppress this mutagenic effect. KP elements can also silence the expression
      of certain other P-element-mediated transgenes in a process called P-element
      dependent silencing (PDS), which is thought to involve the recruitment of
      heterochromatin proteins. To explore the mechanism of this silencing, we have
      mobilized KP elements to create a series of strains that contain single, well
      defined KP insertions that show PDS. To understand the quantitative role of KP
      elements in PDS, these single inserts were combined in a series of crosses to
      obtain genotypes with zero, one, or two KP elements, from which we could examine
      the effect of KP gene dose. The extent of PDS in these genotypes was shown to be
      dose dependent in a logarithmic rather than linear fashion. A logarithmic dose
      dependency is consistent with the KP products interacting with heterochromatic
      proteins in a concentration-dependent manner such that two molecules are needed
      to induce gene silencing.

PMID- 21888572
TI  - Using social marketing to understand the family dinner with working mothers.
AB  - The family dinner is a valued tradition that affords opportunities for social
      interaction and attachment, as well as sharing events of the day, role modeling,
      connectedness, and problem solving. Guided by the social-marketing framework,
      this study explored factors associated with the frequency of the family dinner
      among working mothers with children ages 8-11 years. A qualitative design was
      used, employing focus groups and Atlas-ti software for thematic analysis. Lack of
      time, cost, and exhaustion/lack of energy emerged as barriers. Working mothers
      indicated that a youth-based organization operating as a community partner could
      increase the frequency of the family dinner by helping with homework completion
      during after-school care, thereby providing mothers with the time necessary to
      prepare dinner. This research identified both community partners and working
      mothers as valued resources for prevention strategies. Interventions developed to
      increase family dinner frequency should emphasize the perceived value while
      decreasing the costs/barriers.

PMID- 21888573
TI  - Analysis of factors influencing organic fruit and vegetable purchasing in
      Istanbul, Turkey.
AB  - This article examines the influences on the purchasing decisions of fruit and
      vegetable consumers and presents findings from a survey conducted with 385
      respondents living in urban areas in Istanbul, Turkey. It uses a binary logistic
      model to estimate factor effects in organic fruit and vegetable purchasing in
      Turkey. The results indicate that concern for human health and safety is a key
      factor that influences consumer preferences for organic food. Findings will help
      organic product suppliers understand the key factors influencing consumer
      purchasing and consumption behaviors.

PMID- 21888574
TI  - In search of human placentophagy: a cross-cultural survey of human placenta
      consumption, disposal practices, and cultural beliefs.
AB  - Maternal placentophagy, the consumption of the placenta or "afterbirth" by the
      mother following parturition, is an ubiquitous behavior among eutherian mammals,
      including non-human primates. Here we report on a cross-cultural survey of 179
      human societies regarding the consumption, treatment, and disposal of human
      placenta, in addition to accompanying cultural beliefs and perceptions about the
      organ. The conspicuous absence of cultural traditions associated with maternal
      placentophagy in the cross-cultural ethnographic record raises interesting
      questions relative to its ubiquitous presence among nearly all other mammals, and
      the reasons for its absence (or extreme rarity) among prehistoric/historic and
      contemporary human cultures.

PMID- 21888575
TI  - Household utilization of Manioc (Manihot esculenta Crantz) in Northern
      Mozambique.
AB  - Mozambique is ranked ninth of top manioc (Manihot esculenta Crantz) producing
      countries in the world. Manioc roots are a staple to people living in the
      northern part of the country. Despite this, information on production,
      utilization, postharvest handling, and marketing is scarce. The purpose of this
      baseline study was to document selected information on manioc, from the
      production to marketing stage. To gather this information, 70 focus groups
      consisting of 1,724 participants purposely sampled from 10 districts were engaged
      in discussions using a questionnaire. The results show that manioc is the most
      important crop in terms of contribution to household food security and income in
      the region. Both men and women participate in the delivery of manioc production
      chain. Typically, 5 to 15 varieties identified by local language can be found on
      most farms in the study area. Manioc leaves and roots are the parts of the plant
      used as human food. Sun dried manioc roots are principally marketed within the
      locality of production by individual farmers. This baseline study suggests the
      need for location-targeted interventions as the farmers reported varied
      challenges along the manioc production chain.

PMID- 21888576
TI  - Anemia in rural China's elementary schools: prevalence and correlates in Shaanxi
      province's poor counties.
AB  - Despite growing wealth in China, a significant share of children across rural
      China still have no access to iron-rich foods, vitamins, and other
      micronutrients. Such poor diets may result in high incidences of nutritional
      problems, including anemia. The objective of the study was to increase
      understanding of the extent of anemia, and identify structural correlates of
      anemia in poor Shaanxi province's primary schools. The article shows that the
      overall anemia rate is 21.5 percent when using a blood hemoglobin cutoff of 115
      g/L (39 percent with a cutoff of 120 g/L). We find that those students that are
      boarding at school and eat lunch away from home are more likely to be anemic.
      Children with anemia are found to have lower height for age (HAZ) scores. If this
      part of Shaanxi province is representative of all poor counties in China, these
      findings mean millions of children in poor rural China may be anemic.

PMID- 21888578
TI  - Difficulty in the food environment and the experience of food insecurity among
      refugees resettled in the United States.
AB  - The objective of this cross-sectional study was to assess the prevalence and
      correlates of food insecurity in 281 refugees resettled in the United States.
      Participants were recruited through a resettlement center and word of mouth. In
      addition to measures of socioeconomic status, education, time in the U.S., and
      food insecurity, we also measured individual difficulty in navigating the food
      environment using a food difficulty scale. Only 23% of the sample did not endorse
      any of the food insecurity items. Nearly half of the sample also noted difficulty
      in navigating the food environment. Food insecurity scores above the median were
      predicted by both income and non-income variables. In a multivariable logistic
      model, income and having more than one year of education were associated with
      lower food insecurity (p < .05), while "difficulty in the food environment" was
      associated with high food insecurity (p < .01). Results suggest that income is an
      important constraint but that non-income variables may also be important
      determinants of food insecurity.

PMID- 21888577
TI  - Qualitative perspectives on the use of traditional and nontraditional food venues
      among middle- and low-income women in Eastern North Carolina.
AB  - The purpose of this qualitative study was to examine motivations for use of food
      venues among 23 urban and rural women from eastern North Carolina. Women were
      eligible if they cared for children, were non-Hispanic black or white, and were
      English speakers. Interviews elicited participants' decisions for food venue use.
      Reasons for use of supermarkets were low cost, convenient location,
      quality/availability of specific foods, and customer service. Main reasons for
      use of supercenters were bulk foods at low prices and one-stop shopping. Rural
      and urban nonworking women shopped more frequently at discount superstores
      compared to urban working women.

PMID- 21888579
TI  - Food aversions and cravings during early pregnancy: association with nausea and
      vomiting.
AB  - The prospective cohort study examined whether Ecuadorian women with early
      pregnancy nausea and vomiting (NVP) are more likely to develop food aversions and
      cravings, and if so, whether the specific foods identified as aversive or craved
      are the same as those predicted by the popular maternal-embryo protection
      hypothesis (MEPH). Consistent with MEPH predictions, women with NVP were more
      likely to report increased odor sensitivity and aversions for some predicted
      "toxic" foods and more likely to crave fruits. However, other hypothesis
      predictions were not supported. The relationship of food aversions and cravings
      with NVP appears more complicated than that explained by the MEPH.

PMID- 21888580
TI  - Testing the importance of family solidarity, community structure, information
      access, and social capital in predicting nutrition health knowledge and food
      choices in the Philippines.
AB  - This study investigates the influence of family solidarity, community structure,
      information access, social capital, and socioeconomic status on the extent of
      nutrition and health knowledge (NHK) among primary household meal planners. In
      turn, we pose the question: does this knowledge influence dietary decision
      making? Data are taken from a survey determining socioeconomic impacts of vitamin
      A fortified peanut butter on Philippine households. Questions on the
      relationships of nutrition to health were selected to construct a knowledge index
      on which household respondents could be ranked. We then tested hypotheses
      regarding what types of individual, family-level, and community structural
      characteristics would predict performance on this index. The results indicate
      that the strongest predictors of NHK come from sociological theory related to
      family solidarity and community centrality, in addition to information
      accessibility and household income. Our findings also indicate that NHK
      influences dietary choices with regard to the purchase of a vitamin fortified
      staple food product, which is essential when addressing nutritional deficiency
      problems in developing countries.

PMID- 21888581
TI  - Consumption patterns and preference of milk and milk products among rural and
      urban consumers in semi-arid Kenya.
AB  - Milk consumption in the semi-arid regions of Kenya is not well understood. A
      study was carried out on consumption of milk and milk products in the semi-arid
      region of eastern Kenya. A total of 135 rural and 126 urban households were
      interviewed. Raw milk was the most popular and was consumed by 99% and 84% of
      rural and urban households, respectively. Generally as degree of processing
      increased, the frequency of consumption declined from more than once per day to 1
      2 times a week and eventually to occasionally. Richer households consumed
      significantly (p < .05) more milk and milk products than poor households. Raw
      milk was preferred over pasteurized, ultra high temperature treated, and powdered
      milk because it was cheaper and widely available. In order to improve consumption
      of different milk products, there is need to improve availability particularly in
      the rural areas.

PMID- 21888582
TI  - Does frequent eating out cause undesirable food choices? Association of food away
      from home with food consumption frequencies and obesity among Korean housewives.
AB  - This study examined the relationship among socioeconomic factors, frequency of
      food away from home (FAFH) and food-consumption patterns of 1,070 housewives, and
      the association of those factors with obesity, using data from the third Korea
      National Health and Nutrition Examination Survey. Although lower intakes of
      fruits, meats, and fast foods were associated with seldom eating out, no
      consistent pattern was observed regarding the relationship between the frequency
      of FAFH and food consumption for all groups of housewives. Further analysis
      indicated that obesity rates were lower among housewives aged 20-49 years with 7
      12 years of education and moderate eating-out frequency, compared to older, less
      educated women. It appeared that reducing the frequency of FAFH does not always
      entail desirable food intakes among full-time housewives in Korea. Our findings
      suggest that choosing healthy meals away from home is more important for
      housewives than refraining from eating out.

PMID- 21888583
TI  - Edible wild plants of pastorals at high-altitude grasslands of Gurez Valley,
      Kashmir, India.
AB  - Alpine grasslands of Kashmir are a storehouse of numerous wild edible plants,
      besides serving as summer pastures for the flocks of various ethnic communities.
      Throughout these grasslands, pastorals, nomads, and other indigenous communities
      collect and use these plants in several different ways. This article reports the
      richness, distribution, use, mode of use, and frequency of use of edible wild
      plants by three ethnic communities viz. Bakerwals, Gujjars, and Puhloos (Kashmiri
      herdsmen) from three alpine grasslands of a hitherto unknown Gurez Valley,
      Kashmir. Twenty-six plants under 21 genera and 14 families are reported from the
      surveyed grasslands which are used as wild edibles. Our results indicated that
      for many species, the local names differed between the communities but yet the
      folklore uses were common. Further, the frequency of use also varied between the
      communities, with Bakerwals and Gujjars using the majority of the species while
      the semi-sedentary Puhloos use the least. We hypothesize that this difference in
      the use frequency between the communities is a function of differing working
      nature and the rapid advancement of contemporary societal ideas into their
      culture and hence necessitates the documentation of their traditional practices
      and knowledge at the earliest.

PMID- 21888585
TI  - Nutrition ecology--a concept for systemic nutrition research and integrative
      problem solving.
AB  - Many nutrition-related problems (e.g., obesity) are complex and thus
      characterized by a multitude of components, interrelatedness, associated
      feedbacks, and dynamics. Nutrition ecology is an innovative concept to deal with
      complexity and multidimensionality in nutrition science and practice. Along the
      food supply chain the dimensions health, environment, society, and economy are
      taken into account simultaneously and coequally. By combining special
      disciplinary knowledge with methods and principles of research on complexity and
      knowledge integration, nutrition ecology offers a concept to develop approaches
      to solving complex nutrition-related problems. Accordingly, the conceptual
      background and methodological elements of nutrition ecology are presented and
      discussed.

PMID- 21888586
TI  - Trade and the nutrition transition: strengthening policy for health in the
      Pacific.
AB  - This article describes pathways through which trade policy change in two Pacific
      Island countries has contributed to changes in the food supply, and thereby to
      the nutrition transition. The effect of various trade policies from 1960 to 2005
      on trends in food imports and availability is described, and case studies are
      presented for four foods associated with the nutrition transition and chronic
      disease in the Pacific. Trade policies (including liberalization, export
      promotion, protection of the domestic meat industry and support for foreign
      direct investment) have contributed to a reduced availability of traditional
      staples, and increased availability of foods associated with the nutrition
      transition, including refined cereals (particularly polished rice and white
      flour), meat, fats and oils, and processed food products. This study suggests
      that promoting healthier imports and increasing production of healthier
      traditional foods, in both of which trade policy has an important effect, has the
      potential to improve diets and health, in conjunction with other public health
      intervention.

PMID- 21888587
TI  - Nutritional status adiposity and body composition of Oraon and Sarak females in
      Ranchi District, India--a comparison.
AB  - The Oraon and the Sarak are two distinct ethnic groups with respect to their own
      religion, culture, language, and food habits, and they live in similar
      environmental conditions in Ranchi District in Jharkhand, India. Age differences
      in anthropometric and body composition measurements and nutritional status of
      adult (>=18 years) female Oraons (N = 216) and Sarak (N = 110) were recorded and
      compared. The subjects were categorized into three age groups: < 39 years, 40-59
      years, and <= 60 years. The women in both samples were observed to be suffering
      from a very high degree of chronic energy deficiency (CED; body mass index [BMI]
      < 18.5 kg/m(2) in Oraons = 62.50% and in Saraks = 46.36%). Very low proportions
      of body fat mass (FM) and high percentage of fat-free mass (FFM) were recorded in
      these two adult samples. Linear regression analyses revealed that age had a
      significant impact on all variables and the level of undernutrition and thinness
      increased with age. Oraon women had lower BMI, higher rates of undernutrition,
      and lower percent body fat (PBF) and FM compared to the Sarak women.

PMID- 21888588
TI  - Synbiotic effect of various prebiotics on in vitro activities of probiotic
      lactobacilli.
AB  - In the present study, five Lactobacillus strains were evaluated for their
      viability in presence of different prebiotics viz. inulin, oligofructose,
      lactulose, raftilose, and honey. The viability of lactobacilli was observed
      before and after 5 weeks of refrigerated storage. The doubling time varied from
      5.2 hrs to 9.6 hrs. The lowest doubling time was for Lactobacillus plantarum M5
      followed by L. plantarum Ch1 with inulin. Viability of lactobacilli was greatest
      with inulin. The growth and viability in presence of prebiotics were found to be
      strain-specific. Hence, it could be concluded that the addition of prebiotics
      have a significant effect on probiotics, and hence, a combination of suitable
      Lactobacillus strain(s) with a specific prebiotic could be a viable probiotic
      based functional food approach in administering the beneficial bacteria in-vivo.

PMID- 21888589
TI  - Factors influencing the food choices and eating habits of restaurant chefs in
      northern New Jersey: a pilot study.
AB  - This study was conducted to understand the factors influencing the food habits of
      restaurant chefs in northern New Jersey. Data was collected from participants (N
      = 12) using dietary recalls, and semi-structured interviews based on the socio
      ecological model. Dietary recall analysis revealed multiple nutritional intake
      hazards including skipping meals, and substitution of foods rich in fats and
      sugar for fruits and vegetables, and increased consumption of alcohol.
      Qualitative data analysis revealed that their food habits were influenced by a
      repertoire of individual, organizational, and interpersonal factors. The
      relevance of these findings to nutrition intervention programs for this
      population is discussed.

PMID- 21888592
TI  - Preparation, consumption, and nutritional composition of west African cowpea
      dishes.
AB  - In Africa, nutrient intake deficiencies are widespread. We, therefore,
      investigated the potential contribution of cowpea dishes to the ingestion of
      several macro- and micronutrients. Processors and consumers were interviewed and
      cowpea dishes analyzed. Energy, protein, iron, zinc, and calcium contents ranged
      from 1647 to 2570 kJ, 10 to 25 g, 1 to 35 mg, 1.5 to 3.0 mg, 38 to 380 mg per 100
      g d.w., respectively. The iron and calcium contents were highest in dishes
      containing leaves. The consumption of these dishes should be promoted along with
      research on how to further decrease the associated antinutritional factors of
      traditional cowpea dishes.

PMID- 21888591
TI  - Indigenous perception and characterization of Yanyanku and Ikpiru: two functional
      additives for the fermentation of African locust bean.
AB  - Indigenous perception, processing methods, and physicochemical and
      microbiological characteristics of Yanyanku and Ikpiru, two additives used to
      produce fermented African locust bean condiments, Sonru and Iru, were evaluated.
      According to producers, these additives accelerate the fermentation and soften
      the texture of the condiments. Yanyanku is produced by spontaneous fermentation
      with either Hibiscus sabdariffa or Gossypium hirsutum or Adansonia digitata
      seeds, whereas only Hibiscus sabdariffa seeds are used for Ikpiru. Both
      additives, with pH values ranging between 6.2 and 10 and Bacillus spores varying
      between 5.5 and 8.9 Log(10) (CFU/g), could be considered as softening additives
      or enrichment inocula to produce condiments.

PMID- 21888593
TI  - Comparison of lead and cadmium contents in cruciferous vegetables grown under
      diversified ecological conditions: Cracow region of Poland.
AB  - The aim of the present study was to compare lead and cadmium contents in
      cruciferous vegetables grown under diversified ecological conditions for three
      consecutive years, independently of the climatic and agrotechnical conditions.
      The research was conducted in the Cracow region of Poland and tests vegetables
      near the Steelworks, from ecological farms, and from local markets. The heavy
      metal contents were determined using the validated Atomic Absorption Spectrometry
      method, including electrothermal atomization, with an ET-AAS graphite cuvette
      (Varian AA240Z, made by Varian). Cruciferous vegetables cultivated in the areas
      surrounding the steelworks were characterized by alarmingly high lead content
      versus ecological and commercially available vegetables, while the contents of
      this metal in vegetables from the two latter locations did not differ. It cannot
      be definitively stated that the origin of vegetables influenced their cadmium
      content.

PMID- 21888595
TI  - Seabuckthorn: an underutilized resource for the nutritional security and
      livelihood improvement of rural communities in Uttarakhand Himalaya.
AB  - Seabuckthorn (Hippophae salicifolia) is one of the potential underutilized plant
      species having huge multipurpose benefits including economic and ecological.
      Comparative study of fruit morphology, architecture, and juice yield productivity
      revealed that fruit berries of Seabuckthorn in Mana valley was found superior and
      can provide higher economic return than the berries of other plant species.
      Moreover, awareness programmes related to nutritional worth and development and
      demonstration of value added product resulted in economy generation for local
      inhabitants. Several countries are commercially and ecologically harnessing the
      potential of Seabuckthorn for livelihood enhancement and environmental
      conservation. Correspondingly, in Indian Himalayan region, Seabuckthorn plant can
      also offer benefits of nutrition, food, medicine, cosmetic, etc., to the rural
      people for their socioeconomic development. Findings presented here have
      important connotations in light of upcoming organic food and nutraceutical
      industries in the country. The current study will also help in developing value
      chain of Seabuckthorn in Uttarakhand.

PMID- 21888594
TI  - Comparison of calcium and magnesium contents in cruciferous vegetables grown in
      areas around steelworks, on organic farms, and those available in retail.
AB  - The aim of the present study was to compare calcium and magnesium contents in
      cruciferous vegetables grown under diversified ecological conditions for three
      consecutive years, independently of the climatic and agrotechnical conditions.
      The metal contents were determined using validated Atomic Absorption Spectrometry
      with atomization in the flame (FAAS method; spectrometer: AA240FS Varian). The
      dry mass of various vegetable species cultivated on organic farms contained, in
      most cases, significantly higher or similar calcium and magnesium amounts in
      comparison with those from farms located in the closest vicinity of steelworks
      and those purchased at local markets. Cruciferous vegetables from the two latter
      sources showed comparable contents of the essential minerals under study.

PMID- 21888596
TI  - Assessment of nutrition knowledge and related aspects among first-year Kuwait
      University students.
AB  - Assessing nutrition knowledge of populations assists in drawing strategies for
      education programs. Nutrition-related problems are common in Kuwait, thus data on
      nutrition knowledge are needed. This study involved administration of a
      questionnaire to 1,037 first-year Kuwait University students. The overall
      nutrition knowledge score was rated as fair, with deficiency in specific areas of
      knowledge. Students' dietary habits, attitudes, and interest in nutrition
      information were assessed as fair. Our findings will aid in building a nutrition
      knowledge database in Kuwait. A simplified course on aspects of healthy nutrition
      and lifestyle to all Kuwait University students is highly recommended.

PMID- 21888597
TI  - Intraspecific genotypic diversity in plants.
AB  - Variations in the nuclear DNA, mainly as a result of quantitative modulations of
      DNA repeats belonging to different sequence families of satellite DNA and to the
      activity of transposable elements, have been assessed within several angiosperm
      species. These variations alter the amount and organization of the DNA and
      therefore the genotype, rather than the genome proper. They take place on an
      evolutionary time scale as the result of selection processes after the occurrence
      of uncontrolled events in the genome or may be due to direct responses of plant
      genomes to environmental stimuli that occur under plant-level control within a
      short developmental period of a single generation. These DNA changes are
      correlated to changes in the developmental dynamics and phenotypic
      characteristics of the plants, and the capability to carry out genotypic
      variation is an evolutionary trait that allows plant species to adapt to
      different environmental conditions, as well as to the variability of conditions
      in a given environment. The link between developmental and environmental stimuli
      and repetitive DNA that elicits the intraspecific diversity of plant genotypes
      may provide models of evolutionary change that extend beyond the conventional
      view of evolution by allelic substitution and take into account epigenetic
      effects of the genome structure.

PMID- 21888598
TI  - Coca-colonization and hybridization of diets among the Tz'utujil Maya.
AB  - Biomedical health professionals express increasing concern that rising
      consumption of soft drinks and processed foods in Mayan and Latin American eating
      patterns may lead to detrimental nutritional and health consequences. Scholars
      debate whether the pervading presence of Coca-Cola and Pepsi in developing
      countries represents "Coca-Colonization," synonymous with cultural imperialism,
      or cultural hybridization. Using mixed qualitative and quantitative research
      methods, including participant observation and semi-structured interviews, this
      study explores the development of Coca-Colonization and cultural hybridization
      among the Tz'utujil Maya of Santiago Atitlan, Guatemala. By specifically
      examining biomedical perspectives, cycles of conquest, the political economy,
      religion, celebrations, and the physical environment through the lens of soft
      drinks, this study finds that Coca-Colonization and cultural hybridization are
      complementary rather than mutually exclusive processes that contribute to dietary
      transitions, economic development, and differential health beliefs related to
      soft drink consumption.

PMID- 21888599
TI  - Collecting and learning to identify edible fungi in southeastern Poland: age and
      gender differences.
AB  - The gathering of 17 folk taxa of edible fungi (most commonly Boletus edulis,
      Leccinum spp., Xerocomus spp., Suillus spp., Cantharellus cibarius, Armillaria
      spp., Russula spp., Lactarius salmonicolor, Macrolepiota procera, Boletus
      erythropus) was recorded in three villages in southeast Poland, but only 13 of
      them are gathered by children. Gender and age differences were small (apart from
      the fact that more adults than children collect non-Boletaceae species), and
      relatives of both sexes took part in teaching children about mushrooms, although
      fathers were most frequently mentioned as first teachers. Collecting mushrooms,
      mainly for own use, sometimes for sale, is still a culturally significant
      activity.

PMID- 21888600
TI  - Energy and nutrient intake of Tongan adults estimated by 24-hour recall: the
      importance of local food items.
AB  - Tongan adults show one of the highest prevalences of obesity in the world. The
      present study aims to estimate Tongans' energy and nutrient intakes and food
      sources using a 24-hour recall survey for 14 days targeting 15 men and 19 women.
      The mean (SD) daily energy intake was 12.2 (2.3) MJ for men and 10.6 (2.2) MJ for
      women. Imported foods accounted for about half of their energy and macronutrient
      intakes, but for much less of their micronutrients. Some local food items,
      specifically pork, kava, and sea hare, contributed significantly to their
      vitamin, Fe, and Ca intakes, respectively. These findings suggest that heavy
      reliance on imported foods can lead not only to a high prevalence of obesity, but
      also to micronutrient deficiencies.

PMID- 21888601
TI  - Differences in fatty acid composition between aquatic and terrestrial insects
      used as food in human nutrition.
AB  - Edible insects may be a source of long-chain polyunsaturated fatty acids (LC
      PUFA). The aim of this article is to test for differences in aquatic and
      terrestrial insects used in human nutrition. We implemented linear models and
      discovered that differences in the proportion of LC-PUFA between aquatic and
      terrestrial insects do exist, with terrestrial insects being significantly richer
      in particular omega-6 fatty acids. In conclusion, any kind of insect may provide
      valuable sources of LC-PUFA. Because terrestrial insects are more abundant and
      easier to collect, they can be considered a better source of LC-PUFA than aquatic
      ones.

PMID- 21888602
TI  - Decontamination of aquatic vegetable leaves by removing trace toxic metals during
      pickling process with acetic acid solution.
AB  - The heavy-metal content of aquatic plants is mainly dependent upon their
      ecological system. This study indicated that although the toxic heavy-metal
      contents could be above the recommended maximum levels depending upon their
      concentrations in growing water, they can be decontaminated by pickling with 5%
      acetic acid solution. Almost all Cd, Hg, Ba, or Sb and 99.5% Pb, 96.7% Ag, or
      97.1% Al were removed from Water Spinach leaves by soaking in acetic acid
      solution. For Water-Shield leaves, almost all Cd, Hg, Pb, Ba, or Sb and 95.0% Ag
      or 96.1% Al were removed. For Watercress leaves, almost all Cd, Hg, Ba, or Sb and
      99.0% Pb or 99.7% Ag were removed. For Water Hyacinth leaves, almost all Cd, Ba,
      or Sb and 99.0% Hg, 98.5% Pb, 95.0% Ag, or 98.7% Al were removed.

PMID- 21888603
TI  - Clozapine use in schizophrenia: findings of the Research on Asia Psychotropic
      Prescription (REAP) studies from 2001 to 2009.
AB  - OBJECTIVE: Optimizing treatment and outcomes for people with schizophrenia
      requires understanding of how evidence-based treatments are utilized. Clozapine
      is the most effective antipsychotic drug for treatment-refractory schizophrenia,
      but few studies have investigated trends and patterns of its use over time
      internationally. This study examined the prescription patterns of clozapine and
      its demographic and clinical correlates in Asia from 2001 to 2009. METHOD:
      Clozapine prescriptions were collected in a sample of 6761 hospitalized
      schizophrenia patients in nine Asian countries and regions using a standardized
      protocol and data collection procedure. RESULTS: Overall, the proportion of
      patients receiving clozapine prescriptions was stable across the three surveys
      from 2001 to 2009, ranging from 14.5% to 15.9%. However, the rates and patterns
      observed within different regions and countries at each survey differed
      considerably. Clozapine use decreased significantly over time in China, while it
      increased in Korea and Singapore. Multiple logistic regression analysis revealed
      that patients taking clozapine were significantly younger, had a higher dose of
      antipsychotic drugs in chlorpromazine equivalents, were more likely to be female,
      had fewer extrapyramidal symptoms, and had more negative symptoms, admissions and
      weight gain in the past month than those not receiving clozapine. CONCLUSION: The
      variability in overall rates and changes in prescription rates over time in these
      samples suggest that factors other than psychopharmacological principles play an
      important role in determining the use of clozapine in schizophrenia in Asia.

PMID- 21888604
TI  - Voice and speech range profiles and Voice Handicap Index for males-
      methodological issues and data.
AB  - Reference data for speech range profiles (SRP), voice range profiles (VRP), and
      Voice Handicap Index (VHI) are presented for Swedish males (n = 30). For
      comparisons, individual data for four male contact granuloma patients are also
      reported. For the vocally healthy group mean values were: speaking fundamental
      frequency 123 Hz (SD 12.1), speaking equivalent level, Leq, 72.2 dB (SD 2.1), SRP
      area 142 ST*dB (SD 24.1), and VRP area 1,706 ST*dB (SD 340). Mean VHI was 5 (SD
      4.8). Test-retest recordings of VRP and SRP for three subjects suggested good
      reliability. SRP and VRP values for three of the patients fell more than 2 SD
      outside the reference values. Protocols and results are discussed and
      standardized recording and analyses procedures are suggested.

PMID- 21888606
TI  - What kind of evidence do we need for evidence-based mental health policy? The
      case of the Better Access initiative.

PMID- 21888607
TI  - Australia's Better Access initiative: do the evaluation data support the critics?

PMID- 21888609
TI  - Australia's Better Access initiative: an evaluation.
AB  - BACKGROUND: Australia's Better Access to Psychiatrists, Psychologists and General
      Practitioners through the Medicare Benefits Schedule (Better Access) initiative
      involves a series of Medicare Benefits Schedule (MBS) item numbers which offer a
      rebate for selected services delivered by eligible clinicians. There has been
      considerable debate about the appropriateness and effectiveness of Better Access,
      much of which has been based on limited evidence. The current paper contributes
      to this debate by presenting the findings of a study which profiled the clinical
      and treatment characteristics of Better Access patients and examined the outcomes
      of their care. METHOD: We approached a stratified random sample of providers who
      had billed for at least 100 occasions of service under the Better Access item
      numbers in 2008 (509 clinical psychologists, 640 registered psychologists, 1280
      GPs) and invited them to participate. Those who agreed were asked to recruit 5-10
      Better Access patients according to a specific protocol. We collected data that
      enabled us to profile providers, patients and sessions. We also collected pre-
      and post-treatment patient outcome data, using the Kessler-10 (K-10) and the
      Depression Anxiety Stress Scales (DASS-21). RESULTS: In total, 883 patients were
      recruited into the study (289 by 41 clinical psychologists, 317 by 49 registered
      psychologists and 277 by 39 GPs). More than 90% of participating patients had
      diagnoses of depression and/or anxiety (compared with 13% of the general
      population). More than 80% were experiencing high or very high levels of
      psychological distress (compared with 10% of the general population). Around half
      of all participating patients had no previous history of mental health care.
      Patients experienced statistically significant improvements in average K-10 and
      DASS-21 scores from pre- to post-treatment. CONCLUSIONS: The findings suggest
      that Better Access is playing an important part in meeting the community's
      previously unmet need for mental health care.

PMID- 21888610
TI  - Quick Personality Assessment Schedule (PAS-Q): validation of a brief screening
      test for personality disorders in a population of psychiatric outpatients.
AB  - OBJECTIVE: The internal consistency, test-retest reliability, and validity of the
      Quick Personality Assessment Schedule (PAS-Q), as a screening instrument for
      personality disorders were studied in a random sample of 195 Dutch psychiatric
      outpatients, using the SCID-II as a gold standard. METHOD: All patients were
      interviewed with the PAS-Q. With an interval of 1 to 2 weeks, they were
      interviewed with the SCID-II. Three weeks later the PAS-Q was re-administered.
      RESULTS: According to the SCID-II, 97 patients (50%) were suffering from a
      personality disorder. The PAS-Q correctly classified 81% of all participants.
      Sensitivity and specificity were 0.80 and 0.82, respectively. CONCLUSION: The
      results provide evidence for the usefulness of the PAS-Q as a screening
      instrument for personality disorders in clinical populations.

PMID- 21888608
TI  - A consensus statement for safety monitoring guidelines of treatments for major
      depressive disorder.
AB  - OBJECTIVE: This paper aims to present an overview of screening and safety
      considerations for the treatment of clinical depressive disorders and make
      recommendations for safety monitoring. METHOD: Data were sourced by a literature
      search using MEDLINE and a manual search of scientific journals to identify
      relevant articles. Draft guidelines were prepared and serially revised in an
      iterative manner until all co-authors gave final approval of content. RESULTS:
      Screening and monitoring can detect medical causes of depression. Specific
      adverse effects associated with antidepressant treatments may be reduced or
      identified earlier by baseline screening and agent-specific monitoring after
      commencing treatment. CONCLUSION: The adoption of safety monitoring guidelines
      when treating clinical depression is likely to improve overall physical health
      status and treatment outcome. It is important to implement these guidelines in
      the routine management of clinical depression.

PMID- 21888611
TI  - National depression and anxiety indices for Australia.
AB  - OBJECTIVE: This study aimed to develop a National Depression Index and a National
      Anxiety Index to measure the depression and anxiety status of the Australian
      population, to compare data between surveys, and to compare relative risk in
      different population groups. METHOD: The indices were developed using cross
      sectional data from four surveys: the 1997 and 2007 National Surveys of Mental
      Health and Wellbeing (NSMHWB) and the 2001 and 2004/5 National Health Surveys
      (NHS). Six items from the K10 that most closely related to the ICD-10 diagnosis
      of depression and four that most closely related to a diagnosis of an anxiety
      disorder were used to create separate scales. The indices were developed by
      estimating the predicted probabilities of depression and anxiety on these
      separate K10 scales in the 2007 NSMHWB and then applying these predicted
      probabilities to the same scales in the other surveys. The 1997 NSMHWB and 2001
      NHS were used as benchmarks for the respective surveys, with values greater than
      or less than 100 on the indices indicating a higher or lower probability of
      depression and anxiety in the subsequent survey year. Overall mean risks of
      depression and anxiety were examined along with differences in mean risk by age,
      household income, employment status and geographic location for males and
      females. RESULTS: There was an overall increase in the mean risk of anxiety
      between the 1997 and 2007 NSMHWB but no significant difference in the mean risk
      of depression. Significant increases in the mean risk of anxiety were observed
      for women aged 45-64, for employed men and women, and for women living in the
      inner city and non-regional rural areas. CONCLUSIONS: The increase in the mean
      risk of anxiety may support the need for public education to focus on anxiety
      disorders, particularly for middle-aged women and for employed men and women.

PMID- 21888612
TI  - On narratives and conversations.

PMID- 21888613
TI  - Amisulpride in the treatment of somatoform disorders.

PMID- 21888614
TI  - Comparison of cortical and cancellous bone remodeling of the pelvis after press
      fit cup total hip arthroplasty dependent on patient and prosthesis-specific
      characteristics: a computed tomography-assisted osteodensitometry study in vivo.
AB  - Even though periprosthetic bone loss is common after total hip arthroplasty,
      there is no scientific evidence whether it compromises the survival of the
      prosthesis. Using quantitative computed tomography-assisted osteodensitometry, we
      determined the pattern of periacetabular bone density (BD) changes of two
      different press-fit cups (54 hips) 10 days, 1 year and 3 years post-operatively.
      We measured cortical and cancellous BD at three points of time and evaluated the
      effects of patient-specific characteristics [age, gender, body mass index (BMI)],
      clinical function, and BD at index operation. Cancellous BD decreased in all
      periacetabular regions by up to -52% (p <= 0.001). In contrast, cortical BD above
      the dome of the cup remained constant while at the level of the cup it decreased
      by up to -17% (p <= 0.001). Older patients had significantly lower cortical
      (ventral and dorsal) and cancellous (cranial) BD values, obese patients had a
      higher cortical BD ventral, and patients with excellent clinical results had a
      higher cancellous BD ventral and dorsal to the cup. Changes in BD suggest high
      stress shielding of retroacetabular cancellous bone, while load is transmitted to
      cortical bone above the dome of the cup. Patient-specific characteristics were
      shown to affect BD, but long-term analysis is needed to show whether these
      effects are of clinical importance.

PMID- 21888615
TI  - Rituximab-hyperfractionated cyclophosphamide, vincristine, adriamycin and
      dexamethasone alternating with high-dose cytarabine and methotrexate for
      aggressive non-Hodgkin lymphoma.

PMID- 21888616
TI  - Progressive transformation of germinal centers and Hodgkin lymphoma: more
      insights but maybe more confusion?

PMID- 21888617
TI  - Genetic variability in N-acetyltransferase 2 gene determines susceptibility to
      childhood lymphoid or myeloid leukemia in Brazil.
AB  - Seven single nucleotide polymorphisms (SNPs) were genotyped in 535 Brazilian
      children (158 with acute lymphoblastic leukemia [ALL], 74 with acute myeloid
      leukemia [AML] and 303 controls). The subjects were classified as fast or slow
      acetylators based on their genotypic variants. Logistic regression was used to
      estimate odds ratios (ORs) and 95% confidence intervals. N-acetyltransferase 2
      (NAT2) SNP 341T > C frequency was higher among both leukemia subtypes compared to
      controls. There was also a significant difference in the frequency of SNP 590G >
      A in AML (OR, 1.57, 1.07-2.30). The haplotypes *14A, *5A and *5C conferred an
      increased risk in cases of ALL, while *14E, *6B and *6F conferred an increased
      risk for AML. An age-dependent analysis demonstrated that the NAT2 slow
      acetylators conferred an increased risk association with leukemia in children <=
      1 year old (OR, 7.91, 3.87-16.16) and also in older children (1 >= 10 years old)
      (OR, 1.53, 1.01-2.31). However, in this latter group the magnitude was reduced.
      The results demonstrate that the different NAT2 haplotypes contribute to the risk
      of either ALL or AML.

PMID- 21888618
TI  - Obesity in adult lymphoma survivors.
AB  - As a result of therapeutic advances, survivors of lymphoma are now living longer.
      However, their mortality is higher when compared to the general population,
      probably due to multiple factors. Survivors of childhood leukemia and lymphoma
      appear to have an increased prevalence of obesity. The objectives of this
      retrospective study were to analyze weight change after lymphoma treatment in an
      adult population and determine factors predictive of weight gain. Data were
      collected from 219 patients and analyzed sequentially at the initial visit and at
      6, 12 and 18 months. There was a progressive increase in weight from the initial
      visit to 6 months (1.5% increase of initial body weight), 12 months (4.5%) and 18
      months (6.4%). More than 9% of patients experienced weight gain greater than 20%
      during follow-up. There was a statistically significant association between the
      percentage of increase in weight and age, B symptoms and body mass index (BMI) at
      presentation. Younger patients, those with B symptoms or those with lower BMI
      manifested more weight gain (p = 0.0008, p = 0.0440 and p = 0.0009,
      respectively). Other assessed factors had no effect on weight gain including sex,
      race, lymphoma histology, disease outcome, radiation therapy, number of treatment
      regimens and use of steroids. Further studies are needed to explore long-term
      weight trends and their impact on the health of lymphoma survivors.

PMID- 21888619
TI  - Therapeutic applications of the PhiC31 integrase system.
AB  - The potential use of the PhiC31 integrase system in gene therapy opens up the
      possibilities of new treatments for old diseases. PhiC31 integrase mediates the
      integration of plasmid DNA into the chromsomes of mammalian cells in a sequence
      specific manner, resulting in robust, long-term transgene expression. In this
      article, we review how PhiC31 integrase mediates transgene integration into the
      genomes of target cells and summarize the recent preclinical applications of the
      system to gene therapy. These applications encompass in vivo studies in liver and
      lung, as well as increasing ex vivo uses of the system, including in neural and
      muscle stem cells, in cord-lining epithelial cells, and for the production of
      induced pluripotent stem cells. The safety of the PhiC31 integrase system for
      gene therapy is evaluated, and its ability to provide treatments for hemophilia
      is discussed. We conclude that gene therapy strategies utilizing PhiC31 integrase
      offer great promise for the development of treatments in the future.

PMID- 21888620
TI  - Development of adenovirus hybrid vectors for Sleeping Beauty transposition in
      large mammals.
AB  - The Sleeping Beauty (SB) transposase system for somatic integration offers great
      potential for in vivo gene therapeutic applications and genome engineering. Until
      recently, however, efficacy of SB transposase as a gene transfer vector
      especially in large animals was lacking. Herein, we report about the newest viral
      vector development for delivery of the SB transposase system into large mammals.
      Over the past decade various hyperactive versions of SB transposase and advanced
      adenovirus vectors enabling efficient and safe delivery of transgenes in vivo
      were developed. Already several years ago it was demonstrated that adenovirus
      vectors can be used for delivery of the SB transposase system into murine liver.
      Our newest study showed for the first time that a hyperactive transposase system
      delivered by high-capacity adenoviral vectors can result in somatic integration
      of exogenous DNA in canine liver, facilitating stabilized transgene expression
      and phenotypic correction for up to three years in a canine model of human
      disease. In this review we discuss safety issues and further improvements of this
      adenovirus based hybrid vector system for somatic integration. In the future this
      approach paves new paths towards the possible cure of human genetic diseases and
      novel strategies for in vivo genome engineering in large mammals.

PMID- 21888622
TI  - A global survey of CRM1-dependent nuclear export sequences in the human
      deubiquitinase family.
AB  - The mechanisms that regulate the nucleocytoplasmic localization of human
      deubiquitinases remain largely unknown. The nuclear export receptor CRM1 binds to
      specific amino acid motifs termed NESs (nuclear export sequences). By using in
      silico prediction and experimental validation of candidate sequences, we
      identified 32 active NESs and 78 inactive NES-like motifs in human
      deubiquitinases. These results allowed us to evaluate the performance of three
      programs widely used for NES prediction, and to add novel information to the
      recently redefined NES consensus. The novel NESs identified in the present study
      reveal a subset of 22 deubiquitinases bearing motifs that might mediate their
      binding to CRM1. We tested the effect of the CRM1 inhibitor LMB (leptomycin B) on
      the localization of YFP (yellow fluorescent protein)- or GFP (green fluorescent
      protein)-tagged versions of six NES-bearing deubiquitinases [USP (ubiquitin
      specific peptidase) 1, USP3, USP7, USP21, CYLD (cylindromatosis) and OTUD7B (OTU
      domain-containing 7B)]. YFP-USP21 and, to a lesser extent, GFP-OTUD7B relocated
      from the cytoplasm to the nucleus in the presence of LMB, revealing their
      nucleocytoplasmic shuttling capability. Two sequence motifs in USP21 had been
      identified during our survey as active NESs in the export assay. Using site
      directed mutagenesis, we show that one of these motifs mediates USP21 nuclear
      export, whereas the second motif is not functional in the context of full-length
      USP21.

PMID- 21888621
TI  - Efficacy and safety of Sleeping Beauty transposon-mediated gene transfer in
      preclinical animal studies.
AB  - Sleeping Beauty (SB) transposons have been effective in delivering therapeutic
      genes to treat certain diseases in mice. Hydrodynamic gene delivery of
      integrating transposons to 5-20% of the hepatocytes in a mouse results in
      persistent elevated expression of the therapeutic polypeptides that can be
      secreted into the blood for activity throughout the animal. An alternative route
      of delivery is ex vivo transformation with SB transposons of hematopoietic cells,
      which then can be reintroduced into the animal for treatment of cancer. We
      discuss issues associated with the scale-up of hydrodynamic delivery to the liver
      of larger animals as well as ex vivo delivery. Based on our and others'
      experience with inefficient delivery to larger animals, we hypothesize that
      impulse, rather than pressure, is a critical determinant of the effectiveness of
      hydrodynamic delivery. Accordingly, we propose some alterations in delivery
      strategies that may yield efficacious levels of gene delivery in dogs and swine
      that will be applicable to humans. To ready hydrodynamic delivery for human
      application we address a second issue facing transposons used for gene delivery
      regarding their potential to "re-hop" from one site to another and thereby
      destabilize the genome. The ability to correct genetic diseases through the
      infusion of DNA plasmids remains an appealing goal.

PMID- 21888623
TI  - PEG-liposomal oxaliplatin induces apoptosis in human colorectal cancer cells via
      Fas/FasL and caspase-8.
AB  - Since cellular uptake of PEG [poly(ethylene glycol)]-liposomal L-OHP
      (oxaliplatin) induces bioactive changes in CRC (colorectal cancer), we have
      investigated its apoptotic effect and anticancer mechanism. Human CRC SW480 cells
      were treated with PEG-liposomal L-OHP and a caspase-8 inhibitor [Z-IETD-FMK
      (benzyloxycarbonyl-Ile-Glu-Thr-dl-Asp-fluoromethylketone)]. Apoptosis was
      measured by FCM (flow cytometry) and TUNEL (terminal deoxynucleotidyl transferase
      mediated dUTP nick-end labelling) assay. Expression of Fas/FasL and cytochrome c
      was detected using FCM and an immunofluorescence assay. Expression of caspase-8,
      Bid, caspase-9, caspase-7 and activated caspase-3 (P17) was examined by Western
      blot analyses. The results indicated that PEG-liposomal L-OHP (28 MUg/ml L-OHP)
      induced marked apoptosis in SW480 cells compared with 28 MUg/ml free L-OHP. The
      expression levels of Fas, FasL, cytochrome c, caspase-9, caspase-7 and activated
      caspase-3 proteins were up-regulated, with a corresponding increase in apoptosis;
      however, expression of caspase-8 and Bid were down-regulated as apoptosis
      increased. When cells were treated with Z-IETD-FMK, apoptosis was inhibited, but
      there was little impact on the expression of Fas, FasL, cytochrome c, Bid,
      caspase-9, caspase-7 and activated caspase-3. These findings indicate that PEG
      liposomal L-OHP enhances the anticancer potency of the chemotherapeutic agent;
      moreover, Fas/FasL and caspase-8 signalling pathways play a key role in mediating
      PEG-liposomal L-OHP-induced apoptosis.

PMID- 21888624
TI  - Low triglyceride levels are associated with a better metabolic control in
      patients with type 1 diabetes.
AB  - BACKGROUND: Although it is well known in the literature that high triglyceride
      serum (TG) levels can jeopardize the metabolic control, little is known about the
      influence of low TG on type 1 diabetes patients (T1D). The aim of this study is
      to investigate the distribution of TG serum levels in individuals with T1D and
      its relationship with metabolic control. FINDINGS: We reviewed the medical charts
      of 180 patients with T1D, who were classified in groups according to TG levels:
      1) low (below 50 mg/dL); 2) normal (50-150 mg/dL); 3) high (above 150 mg/dL). TG
      were low in 21.1% (n = 38; group 1), normal in 68.6% (n = 123; group 2) and high
      in 10.6% (n = 19; group 3). High TG was associated with a poor metabolic control
      (p < 0.001). Patients with TG lower than 50 mg/dL had a lower HbA1c than those
      with TG between 50 and 150 mg/dL (7.41+/-1.50% vs 8.56%+/-1.94%; p = 0.002).
      CONCLUSION: TG lower than 50 mg/dL was common and might be associated with a
      better metabolic control in patients with T1D, although it is not clear whether
      the former is the cause or consequence for the latter.

PMID- 21888625
TI  - Metastatic breast carcinoma mimicking a sebaceous gland neoplasm: a case report.
AB  - INTRODUCTION: Breast cancer is common in women and its metastases involve the
      skin in approximately one quarter of patients. Accordingly, metastatic breast
      cancer shown to be cutaneous through histology must be distinguished from a wide
      variety of other neoplasms as well as the diverse morphologic variants of breast
      cancer itself. CASE PRESENTATION: We report the case of a 61-year-old Caucasian
      woman with cutaneous metastases of a bilateral ductal breast carcinoma that in
      histopathological examination mimicked an adnexal neoplasm with sebaceous
      differentiation. CONCLUSION: Against the background of metastatic breast
      carcinoma, dermatopathological considerations of sebaceous differentiation of
      skin lesions are presented and discussed focusing on the rare differential
      diagnosis of sebaceous carcinoma of the breast.

PMID- 21888626
TI  - Sirenomelia in a Nigerian triplet: a case report.
AB  - INTRODUCTION: Sirenomelia, also known as mermaid syndrome, is a very rare fatal
      congenital abnormality in which the legs are fused together, giving them the
      appearance of a mermaid's tail. It is commonly associated with abnormal kidney
      development, genital and rectal abnormalities. A handful of cases have been
      reported in other parts of the world, however, no cases have previously been
      reported in a Nigerian neonate. To the best of our knowledge, we believe that
      this is the first case reported from West Africa and in a triplet. CASE
      PRESENTATION: A 16-hour-old baby boy, the second of a set of Nigerian triplets,
      presented to our facility with fusion of the entire lower limbs, imperforate
      anus, indiscernible genital structures, single umbilical artery and a neural tube
      defect. His parents were from the Hausa ethnic group and not related. CONCLUSION:
      Sirenomelia has not been previously described in a set of triplets, and it is
      hoped that this report from West Africa will give information about the non
      racial predilection of this condition.

PMID- 21888627
TI  - Evaluation of prognostic and predictive value of microtubule associated protein
      tau in two independent cohorts.
AB  - INTRODUCTION: Microtubule associated proteins (MAPs) endogenously regulate
      microtubule stabilization and have been reported as prognostic and predictive
      markers for taxane response. The microtubule stabilizer, MAP-tau, has shown
      conflicting results. We quantitatively assessed MAP-tau expression in two
      independent breast cancer cohorts to determine prognostic and predictive value of
      this biomarker. METHODS: MAP-tau expression was evaluated in the retrospective
      Yale University breast cancer cohort (n = 651) using tissue microarrays and also
      in the TAX 307 cohort, a clinical trial randomized for TAC versus FAC
      chemotherapy (n = 140), using conventional whole tissue sections. Expression was
      measured using the AQUA method for quantitative immunofluorescence. Scores were
      correlated with clinicopathologic variables, survival, and response to therapy.
      RESULTS: Assessment of the Yale cohort using Cox univariate analysis indicated an
      improved overall survival (OS) in tumors with a positive correlation between high
      MAP-tau expression and overall survival (OS) (HR = 0.691, 95% CI = 0.489-0.974; P
      = 0.004). Kaplan Meier analysis showed 10-year survival for 65% of patients with
      high MAP-tau expression compared to 52% with low expression (P = .006). In TAX
      307, high expression was associated with significantly longer median time to
      tumor progression (TTP) regardless of treatment arm (33.0 versus 23.4 months, P =
      0.010) with mean TTP of 31.2 months. Response rates did not differ by MAP-tau
      expression (P = 0.518) or by treatment arm (P = 0.584). CONCLUSIONS: Quantitative
      measurement of MAP-tau expression has prognostic value in both cohorts, with high
      expression associated with longer TTP and OS. Differences by treatment arm or
      response rate in low versus high MAP-tau groups were not observed, indicating
      that MAP-tau is not associated with response to taxanes and is not a useful
      predictive marker for taxane-based chemotherapy.

PMID- 21888628
TI  - Comparison of radioimmuno and carbon nanotube field-effect transistor assays for
      measuring insulin-like growth factor-1 in a preclinical model of human breast
      cancer.
AB  - BACKGROUND: To realize the promise of personalized medicine, diagnostic
      instruments used for detecting and measuring biomarkers must become smaller,
      faster and less expensive. Although most techniques used currently to detect
      biomarkers are sensitive and specific, many suffer from several disadvantages
      including their complexity, high cost and long turnaround time. One strategy to
      overcome these problems is to exploit carbon nanotube (CNT) based biosensors,
      which are sensitive, use inexpensive disposable components and can be easily
      adapted to current assay protocols. In this study we investigated the
      applicability of using a CNT field-effect transistor (CNT-FET) as a diagnostic
      instrument for measuring cancer biomarkers in serum using a mouse model of Breast
      Cancer Susceptibility 1-related breast cancer. Insulin like growth factor-1 (IGF
      1) was chosen because it is highly relevant in breast cancer and because
      measuring serum IGF-1 levels by conventional methods is complicated due to
      specific IGF-1 serum binding proteins. FINDINGS: Our results show that there is
      good correlation between the two platforms with respect to detecting serum IGF-1.
      In fact, the CNT-FETs required only one antibody, gave real-time results and
      required approximately 100-fold less mouse serum than the radioimmunoassay.
      CONCLUSIONS: Both IGF-1 radioimmuno and CNT-FET assays gave comparable results.
      Indeed, the CNT-FET assay was simpler and faster than the radioimmunoassay.
      Additionally, the low serum sample required by CNT-FETs can be especially
      advantageous for studies constricted by limited amount of human clinical samples
      and for mouse studies, since animals often need to be sacrificed to obtain enough
      serum for biomarker evaluation.

PMID- 21888629
TI  - Conversion of deoxynivalenol to 3-acetyldeoxynivalenol in barley-derived fuel
      ethanol co-products with yeast expressing trichothecene 3-O-acetyltransferases.
AB  - BACKGROUND: The trichothecene mycotoxin deoxynivalenol (DON) may be concentrated
      in distillers dried grains with solubles (DDGS; a co-product of fuel ethanol
      fermentation) when grain containing DON is used to produce fuel ethanol. Even low
      levels of DON (<= 5 ppm) in DDGS sold as feed pose a significant threat to the
      health of monogastric animals. New and improved strategies to reduce DON in DDGS
      need to be developed and implemented to address this problem. Enzymes known as
      trichothecene 3-O-acetyltransferases convert DON to 3-acetyldeoxynivalenol
      (3ADON), and may reduce its toxicity in plants and animals. RESULTS: Two Fusarium
      trichothecene 3-O-acetyltransferases (FgTRI101 and FfTRI201) were cloned and
      expressed in yeast (Saccharomyces cerevisiae) during a series of small-scale
      ethanol fermentations using barley (Hordeum vulgare). DON was concentrated 1.6 to
      8.2 times in DDGS compared with the starting ground grain. During the
      fermentation process, FgTRI101 converted 9.2% to 55.3% of the DON to 3ADON,
      resulting in DDGS with reductions in DON and increases in 3ADON in the Virginia
      winter barley cultivars Eve, Thoroughbred and Price, and the experimental line
      VA06H-25. Analysis of barley mashes prepared from the barley line VA04B-125
      showed that yeast expressing FfTRI201 were more effective at acetylating DON than
      those expressing FgTRI101; DON conversion for FfTRI201 ranged from 26.1% to
      28.3%, whereas DON conversion for FgTRI101 ranged from 18.3% to 21.8% in VA04B
      125 mashes. Ethanol yields were highest with the industrial yeast strain Ethanol
      Red(r), which also consumed galactose when present in the mash. CONCLUSIONS: This
      study demonstrates the potential of using yeast expressing a trichothecene 3-O
      acetyltransferase to modify DON during commercial fuel ethanol fermentation.

PMID- 21888630
TI  - Tubular immunostimulating complex based on cucumarioside A2-2 and
      monogalactosyldiacylglycerol from marine macrophytes.
AB  - BACKGROUND: There is an urgent need to develop safe and effective adjuvants for
      the new generation of subunit vaccines. We developed the tubular
      immunostimulating complex (TI-complex) as a new nanoparticulate antigen delivery
      system. The morphology and composition of TI-complexes principally differ from
      the known vesicular immunostimulating complexes (ISCOMs). However, methodology
      for the preparation of TI-complexes has suffered a number of shortcomings. The
      aim of the present work was to obtain an antigen carrier consisting of triterpene
      glycosides from Cucumaria japonica, cholesterol, and monogalactosyldiacylglycerol
      from marine macrophytes with reproducible properties and high adjuvant activity.
      RESULTS: The cucumarioside A2-2 - cholesterol - MGalDG ratio of 6:2:4 (by weight)
      was found to provide the most effective formation of TI-complexes and the minimum
      hemolytic activity in vitro. Tubules of TI-complexes have an outer diameter of
      about 16 nm, an inner diameter of 6 nm, and a length of 500 nm. A significant
      dilution by the buffer gradually destroyed the tubular nanoparticles. The TI
      complex was able to increase the immunogenicity of the protein antigens from
      Yersinia pseudotuberculosis by three to four times. CONCLUSIONS: We propose an
      optimized methodology for the preparation of homogeneous TI-complexes containing
      only tubular particles, which would achieve reproducible immunization results. We
      suggest that the elaborated TI-complexes apply as a universal delivery system for
      different subunit antigens within anti-infectious vaccines and enhance their
      economic efficacy and safety.

PMID- 21888632
TI  - Temporal trends (1977-2007) and ethnic inequity in child mortality in rural
      villages of southern Guinea Bissau.
AB  - BACKGROUND: Guinea Bissau is one of the poorest countries in the world, with one
      of the highest under-5 mortality rate. Despite its importance for policy
      planning, data on child mortality are often not available or of poor quality in
      low-income countries like Guinea Bissau. Our aim in this study was to use the
      baseline survey to estimate child mortality in rural villages in southern Guinea
      Bissau for a 30 years period prior to a planned cluster randomised intervention.
      We aimed to investigate temporal trends with emphasis on historical events and
      the effect of ethnicity, polygyny and distance to the health centre on child
      mortality. METHODS: A baseline survey was conducted prior to a planned cluster
      randomised intervention to estimate child mortality in 241 rural villages in
      southern Guinea Bissau between 1977 and 2007. Crude child mortality rates were
      estimated by Kaplan-Meier method from birth history of 7854 women. Cox regression
      models were used to investigate the effects of birth periods with emphasis on
      historical events, ethnicity, polygyny and distance to the health centre on child
      mortality. RESULTS: High levels of child mortality were found at all ages under
      five with a significant reduction in child mortality over the time periods of
      birth except for 1997-2001. That period comprises the 1998/99 civil war interval,
      when child mortality was 1.5% higher than in the previous period. Children of
      Balanta ethnic group had higher hazard of dying under five years of age than
      children from other groups until 2001. Between 2002 and 2007, Fula children
      showed the highest mortality. Increasing walking distance to the nearest health
      centre increased the hazard, though not substantially, and polygyny had a
      negligible and statistically not significant effect on the hazard. CONCLUSION:
      Child mortality is strongly associated with ethnicity and it should be considered
      in health policy planning. Child mortality, though considerably decreased during
      the past 30 years, remains high in rural Guinea Bissau. Temporal trends also
      suggest that civil wars have detrimental effects on child mortality. TRIAL
      REGISTRATION: Current Controlled Trials ISRCTN52433336.

PMID- 21888631
TI  - Effects of short-term glucocorticoid treatment on changes in cartilage matrix
      degradation and chondrocyte gene expression induced by mechanical injury and
      inflammatory cytokines.
AB  - INTRODUCTION: Traumatic joint injury damages cartilage and causes adjacent joint
      tissues to release inflammatory cytokines, increasing the risk of developing
      osteoarthritis. The main objective of this study was to determine whether the
      combined catabolic effects of mechanical injury, tumor necrosis factor alpha
      (TNFalpha) and interleukin-6 (IL-6)/soluble IL-6 receptor (sIL-6R) on cartilage
      could be abolished by short-term treatment with glucocorticoids such as
      dexamethasone. METHODS: In an initial dexamethasone-dose-response study, bovine
      cartilage explants were treated with TNFalpha and increasing concentrations of
      dexamethasone. Bovine and human cartilage explants were then subjected to
      individual and combined treatments with TNFalpha, IL-6/sIL-6R and injury in the
      presence or absence of dexamethasone. Treatment effects were assessed by
      measuring glycosaminoglycans (GAG) release to the medium and synthesis of
      proteoglycans. Additional experiments tested whether pre-exposure of cartilage to
      dexamethasone could prevent GAG loss and inhibition of biosynthesis induced by
      cytokines, and whether post-treatment with dexamethasone could diminish the
      effects of pre-established cytokine insult. Messenger ribonucleic acid (mRNA)
      levels for genes involved in cartilage homeostasis (proteases, matrix molecules,
      cytokines, growth and transcription factors) were measured in explants subjected
      to combined treatments with injury, TNFalpha and dexamethasone. To investigate
      mechanisms associated with dexamethasone regulation of chondrocyte metabolic
      response, glucocorticoid receptor (GR) antagonist (RU486) and proprotein
      convertase inhibitor (RVKR-CMK) were used. RESULTS: Dexamethasone dose
      dependently inhibited GAG loss and the reduction in biosynthesis caused by
      TNFalpha. The combination of mechanical injury, TNFalpha and IL-6/sIL-6R caused
      the most severe GAG loss; dexamethasone reduced this GAG loss to control levels
      in bovine and human cartilage. Additionally, dexamethasone pre-treatment or post
      treatment of bovine explants lowered GAG loss and increased proteoglycan
      synthesis in cartilage explants exposed to TNFalpha. Dexamethasone did not down
      regulate aggrecanase mRNA levels. Post-transcriptional regulation by
      dexamethasone of other genes associated with responses to injury and cytokines
      was noted. GR antagonist reversed the effect of dexamethasone on sulfate
      incorporation. RVKR-CMK significantly reduced GAG loss caused by TNFalpha + IL-6
      + injury. CONCLUSIONS: Short-term glucocorticoid treatment effectively abolished
      the catabolic effects exerted by the combination of pro-inflammatory cytokines
      and mechanical injury: dexamethasone prevented proteoglycan degradation and
      restored biosynthesis. Dexamethasone appears to regulate the catabolic response
      of chondrocytes post-transcriptionally, since the abundance of transcripts
      encoding aggrecanases was still elevated in the presence of dexamethasone.

PMID- 21888633
TI  - Nanopatterning on silicon surface using atomic force microscopy with diamond-like
      carbon (DLC)-coated Si probe.
AB  - Atomic force microscope (AFM) equipped with diamond-like carbon (DLC)-coated Si
      probe has been used for scratch nanolithography on Si surfaces. The effect of
      scratch direction, applied tip force, scratch speed, and number of scratches on
      the size of the scratched geometry has been investigated. The size of the groove
      differs with scratch direction, which increases with the applied tip force and
      number of scratches but decreases slightly with scratch speed. Complex
      nanostructures of arrays of parallel lines and square arrays are further
      fabricated uniformly and precisely on Si substrates at relatively high scratch
      speed. DLC-coated Si probe has the potential to be an alternative in AFM-based
      scratch nanofabrication on hard surfaces.

PMID- 21888634
TI  - Two novel low-power and high-speed dynamic carbon nanotube full-adder cells.
AB  - In this paper, two novel low-power and high-speed carbon nanotube full-adder
      cells in dynamic logic style are presented. Carbon nanotube field-effect
      transistors (CNFETs) are efficient in designing a high performance circuit. To
      design our full-adder cells, CNFETs with three different threshold voltages (low
      threshold, normal threshold, and high threshold) are used. First design generates
      SUM and COUT through separate transistors, and second design is a multi-output
      dynamic full adder. Proposed full adders are simulated using HSPICE based on
      CNFET model with 0.9 V supply voltages. Simulation result shows that the proposed
      designs consume less power and have low power-delay product compared to other
      CNFET-based full-adder cells.

PMID- 21888635
TI  - Intracranial internal carotid aneurysm causing diplopia.
AB  - Internal carotid intracranial aneurysms are a relatively rare form of
      intracranial aneurysm that presents with diplopia, retro-orbital pain and
      unilateral headaches. The symptoms are progressive and the diagnosis should be
      considered in a patient presenting with these complaints. Underlying hypertension
      and advanced age are specific risk factors.

PMID- 21888636
TI  - Anisotropic in-plane spin splitting in an asymmetric (001) GaAs/AlGaAs quantum
      well.
AB  - The in-plane spin splitting of conduction-band electron has been investigated in
      an asymmetric (001) GaAs/AlxGa1-xAs quantum well by time-resolved Kerr rotation
      technique under a transverse magnetic field. The distinctive anisotropy of the
      spin splitting was observed while the temperature is below approximately 200 K.
      This anisotropy emerges from the combined effect of Dresselhaus spin-orbit
      coupling plus asymmetric potential gradients. We also exploit the temperature
      dependence of spin-splitting energy. Both the anisotropy of spin splitting and
      the in-plane effective g-factor decrease with increasing temperature.PACS:
      78.47.jm, 71.70.Ej, 75.75.+a, 72.25.Fe.

PMID- 21888637
TI  - Phase II study of weekly paclitaxel and capecitabine in patients with metastatic
      or recurrent esophageal squamous cell carcinoma.
AB  - BACKGROUND: This phase II study assessed the response rate and toxicity profile
      of weekly paclitaxel and capecitabine in patients with metastatic or recurrent
      squamous cell carcinoma of the esophagus (SCCE) METHODS: Patients with
      histologically confirmed SCCE were treated with paclitaxel 80 mg/m(2)
      intravenously on days 1 and 8 plus capecitabine 900 mg/m(2) orally twice a day on
      days 1-14. Treatment cycles were repeated every 3 weeks until disease progression
      or unacceptable toxicity. RESULTS: Between 2006 and 2009, 32 patients were
      enrolled. Twelve patients were chemotherapy-naive. Twenty patients had received
      prior chemotherapy including platinum-based regimens. Patients received a median
      of 5 cycles of treatment (range, 1-12). The response rate was 75% (95%CI;
      50.5~99.5%) in the first-line and 45% (95%CI; 26.9~73.1%) in the second-line.
      With a median follow-up of 20.7 months, median progression-free survival was 5.2
      months (95% CI, 4.0 to 6.4) for all patients and median overall survival (OS) was
      11.7 months (95% CI, 5.5 to 18.0) for all patients. The median OS was 14.3 months
      (95% CI, 10.6 to 18.0) for patients receiving therapy as 1st line and 8.4 months
      (95% CI, 6.6 to 10.1) for those receiving as 2nd-line therapy. Grade 3/4
      neutropenia was observed in 53.3% of the patients, which was the most common
      cause of dose reduction. G3 non-hematologic toxicity included stomatitis (9.4%),
      asthenia (6.3%), and hand-foot skin reaction (3.1%). CONCLUSIONS: Weekly
      paclitaxel and capecitabine is a highly active and well-tolerated regimen in
      patients with metastatic or recurrent SCCE in the first-line as well as second
      line setting.

PMID- 21888638
TI  - Reexpansion pulmonary edema following a posttraumatic pneumothorax: a case report
      and review of the literature.
AB  - The reexpansion pulmonary edema is a rare, but life threatening complication of
      a pneumothorax. Early recognition and a fast symptom orientated therapy are
      necessary for a good outcome. Several cases after non traumatic pneumothoraces
      are reported. We describe a patient who presented with a post-traumatic right
      pneumothorax. After the insertion of a chest tube he developed a reexpansion
      pulmonary edema, which had to be treated by an intubation.Additionally, a review
      of the literature regarding case reports of reexpansion pulmonary edema is
      presented.

PMID- 21888639
TI  - Organic-skinned inorganic nanoparticles: surface-confined polymerization of 6-(3
      thienyl)hexanoic acid bound to nanocrystalline TiO2.
AB  - There are many practical difficulties in direct adsorption of polymers onto
      nanocrystalline inorganic oxide surface such as Al2O3 and TiO2 mainly due to the
      insolubility of polymers in solvents or polymer agglomeration during adsorption
      process. As an alternative approach to the direct polymer adsorption, we propose
      surface-bound polymerization of pre-adsorbed monomers. 6-(3-Thienyl)hexanoic acid
      (THA) was used as a monomer for poly[3-(5-carboxypentyl)thiophene-2,5-diyl]
      (PTHA). PTHA-coated nanocrystalline TiO2/FTO glass electrodes were prepared by
      immersing THA-adsorbed electrodes in FeCl3 oxidant solution. Characterization by
      ultraviolet/visible/infrared spectroscopy and thermal analysis showed that the
      monolayer of regiorandom-structured PTHA was successfully formed from
      intermolecular bonding between neighbored THA surface-bound to TiO2. The
      anchoring functional groups (-COOH) of the surface-crawling PTHA were completely
      utilized for strong bonding to the surface of TiO2.

PMID- 21888640
TI  - Solid-phase molecular recognition of cytosine based on proton-transfer reaction.
      Part II. supramolecular architecture in the cocrystals of cytosine and its 5
      Fluoroderivative with 5-Nitrouracil.
AB  - BACKGROUND: Cytosine is a biologically important compound owing to its natural
      occurrence as a component of nucleic acids. Cytosine plays a crucial role in
      DNA/RNA base pairing, through several hydrogen-bonding patterns, and controls the
      essential features of life as it is involved in genetic codon of 17 amino acids.
      The molecular recognition among cytosines, and the molecular heterosynthons of
      molecular salts fabricated through proton-transfer reactions, might be used to
      investigate the theoretical sites of cytosine-specific DNA-binding proteins and
      the design for molecular imprint. RESULTS: Reaction of cytosine (Cyt) and 5
      fluorocytosine (5Fcyt) with 5-nitrouracil (Nit) in aqueous solution yielded two
      new products, which have been characterized by single-crystal X-ray diffraction.
      The products include a dihydrated molecular salt (CytNit) having both ionic and
      neutral hydrogen-bonded species, and a dihydrated cocrystal of neutral species
      (5FcytNit). In CytNit a protonated and an unprotonated cytosine form a triply
      hydrogen-bonded aggregate in a self-recognition ion-pair complex, and this dimer
      is then hydrogen bonded to one neutral and one anionic 5-nitrouracil molecule. In
      5FcytNit the two neutral nucleobase derivatives are hydrogen bonded in pairs. In
      both structures conventional N-H...O, O-H...O, N-H+...N and N-H...N-
      intermolecular interactions are most significant in the structural assembly.
      CONCLUSION: The supramolecular structure of the molecular adducts formed by
      cytosine and 5-fluorocytosine with 5-nitrouracil, CytNit and 5FcytNit,
      respectively, have been investigated in detail. CytNit and 5FcytNit exhibit
      widely differing hydrogen-bonding patterns, though both possess layered
      structures. The crystal structures of CytNit (Dpka = -0.7, molecular salt) and
      5FcytNit (Dpka = -2.0, cocrystal) confirm that, at the present level of knowledge
      about the nature of proton-transfer process, there is not a strict correlation
      between the Dpka values and the proton transfer, in that the acid/base pka
      strength is not a definite guide to predict the location of H atoms in the solid
      state. Eventually, the absence in 5FcytNit of hydrogen bonds involving fluorine
      is in agreement with findings that covalently bound fluorine hardly ever acts as
      acceptor for available Bronsted acidic sites in the presence of competing
      heteroatom acceptors.

PMID- 21888641
TI  - Long-term consequences of an intensive care unit stay in older critically ill
      patients: design of a longitudinal study.
AB  - BACKGROUND: Modern methods in intensive care medicine often enable the survival
      of older critically ill patients. The short-term outcomes for patients treated in
      intensive care units (ICUs), such as survival to hospital discharge, are well
      documented. However, relatively little is known about subsequent long-term
      outcomes. Pain, anxiety and agitation are important stress factors for many
      critically ill patients. There are very few studies concerned with pain, anxiety
      and agitation and the consequences in older critically ill patients. The overall
      aim of this study is to identify how an ICU stay influences an older person's
      experiences later in life. More specific, this study has the following
      objectives: (1) to explore the relationship between pain, anxiety and agitation
      during ICU stays and experiences of the same symptoms in later life; and (2) to
      explore the associations between pain, anxiety and agitation experienced during
      ICU stays and their effect on subsequent health-related quality of life, use of
      the health care system (readmissions, doctor visits, rehabilitation, medication
      use), living situation, and survival after discharge and at 6 and 12 months of
      follow-up. METHODS/DESIGN: A prospective, longitudinal study will be used for
      this study. A total of 150 older critically ill patients in the ICU will
      participate (ICU group). Pain, anxiety, agitation, morbidity, mortality, use of
      the health care system, and health-related quality of life will be measured at 3
      intervals after a baseline assessment. Baseline measurements will be taken 48
      hours after ICU admission and one week thereafter. Follow-up measurements will
      take place 6 months and 12 months after discharge from the ICU. To be able to
      interpret trends in scores on outcome variables in the ICU group, a comparison
      group of 150 participants, matched by age and gender, recruited from the Swiss
      population, will be interviewed at the same intervals as the ICU group.
      DISCUSSION: Little research has focused on long term consequences after ICU
      admission in older critically ill patients. The present study is specifically
      focussing on long term consequences of stress factors experienced during ICU
      admission. TRIAL REGISTRATION: ISRCTN52754370.

PMID- 21888642
TI  - Feasibility and antihypertensive effect of replacing regular salt with mineral
      salt -rich in magnesium and potassium- in subjects with mildly elevated blood
      pressure.
AB  - BACKGROUND: High salt intake is linked to hypertension whereas a restriction of
      dietary salt lowers blood pressure (BP). Substituting potassium and/or magnesium
      salts for sodium chloride (NaCl) may enhance the feasibility of salt restriction
      and lower blood pressure beyond the sodium reduction alone. The aim of this study
      was to determine the feasibility and effect on blood pressure of replacing NaCl
      (Regular salt) with a novel mineral salt [50% sodium chloride and rich in
      potassium chloride (25%), magnesium ammonium potassium chloride, hydrate (25%)]
      (Smart Salt). METHODS: A randomized, double-blind, placebo-controlled study was
      conducted with an intervention period of 8-weeks in subjects (n = 45) with
      systolic (S)BP 130-159 mmHg and/or diastolic (D)BP 85-99 mmHg. During the
      intervention period, subjects consumed processed foods salted with either NaCl or
      Smart Salt. The primary endpoint was the change in SBP. Secondary endpoints were
      changes in DBP, daily urine excretion of sodium (24-h dU-Na), potassium (dU-K)
      and magnesium (dU-Mg). RESULTS: 24-h dU-Na decreased significantly in the Smart
      Salt group (-29.8 mmol; p = 0.012) and remained unchanged in the control group:
      resulting in a 3.3 g difference in NaCl intake between the groups. Replacement of
      NaCl with Smart Salt resulted in a significant reduction in SBP over 8 weeks (
      7.5 mmHg; p = 0.016). SBP increased (+3.8 mmHg, p = 0.072) slightly in the
      Regular salt group. The difference in the change of SBP between study groups was
      significant (p < 0.002). CONCLUSIONS: The substitution of Smart Salt for Regular
      salt in subjects with high normal or mildly elevated BP resulted in a significant
      reduction in their daily sodium intake as well as a reduction in SBP.

PMID- 21888643
TI  - Atypical presentations and rare metastatic sites of renal cell carcinoma: a
      review of case reports.
AB  - Renal cell carcinoma is a potentially lethal cancer with aggressive behavior and
      a propensity for metastatic spread. Due to the fact that the patterns of
      metastases from renal cell carcinomas are not clearly defined, there have been
      several reports of cases of renal cell carcinoma associated with rare metastatic
      sites and atypical presenting symptoms. The present review focuses on these
      atypical rare clinical presentations of renal cell carcinomas both at the time of
      diagnosis of the primary tumor but also in the years after radical nephrectomy.

PMID- 21888645
TI  - Socioeconomic status and race/ethnicity independently predict health decline
      among older diabetics.
AB  - BACKGROUND: There are pervasive racial and socioeconomic differences in health
      status among older adults with type 2 diabetes. The extent to which racial/ethnic
      and socioeconomic disparities unfold to differential health outcomes has yet to
      be investigated among older adults with diabetes. This study examines whether or
      not race/ethnicity and SES are independent predictors of steeper rates of decline
      in self-rated health among older adults in the U.S. with type 2 diabetes.
      METHODS: The study population was a subset of diabetic adults aged 65 and older
      from the Health and Retirement Study. Respondents were followed up to 16 years.
      Multilevel cumulative logit regression models were used to examine the
      contributions of socioeconomic indicators, race/ethnicity, and covariates over
      time. Health decline was measured as a change in self-reported health status over
      the follow-up period. RESULTS: Relative to whites, blacks had a significantly
      lower cumulative odds of better health status over time (OR: 0.61, p < .0001).
      Hispanics reported significantly lower cumulative odds better health over time
      relative to whites (OR: 0.59, p < .05). Although these disparities narrowed when
      socioeconomic characteristics were added to the model, significant differences
      remained. Including socioeconomic status did not remove the health effects of
      race/ethnicity among blacks and Hispanics. CONCLUSIONS: The author found that
      race/ethnicity and some socioeconomic indicators were independent predictors of
      health decline among older adults with diabetes.

PMID- 21888644
TI  - In vitro toxicity of particulate matter (PM) collected at different sites in the
      Netherlands is associated with PM composition, size fraction and oxidative
      potential--the RAPTES project.
AB  - BACKGROUND: Ambient particulate matter (PM) exposure is associated with
      respiratory and cardiovascular morbidity and mortality. To what extent such
      effects are different for PM obtained from different sources or locations is
      still unclear. This study investigated the in vitro toxicity of ambient PM
      collected at different sites in the Netherlands in relation to PM composition and
      oxidative potential. METHOD: PM was sampled at eight sites: three traffic sites,
      an underground train station, as well as a harbor, farm, steelworks, and urban
      background location. Coarse (2.5-10 MUm), fine (< 2.5 MUm) and quasi ultrafine PM
      (qUF; < 0.18 MUm) were sampled at each site. Murine macrophages (RAW 264.7 cells)
      were exposed to increasing concentrations of PM from these sites (6.25-12.5-25-50
      100 MUg/ml; corresponding to 3.68-58.8 MUg/cm2). Following overnight incubation,
      MTT-reduction activity (a measure of metabolic activity) and the release of pro
      inflammatory markers (Tumor Necrosis Factor-alpha, TNF-alpha; Interleukin-6, IL
      6; Macrophage Inflammatory Protein-2, MIP-2) were measured. The oxidative
      potential and the endotoxin content of each PM sample were determined in a DTT-
      and LAL-assay respectively. Multiple linear regression was used to assess the
      relationship between the cellular responses and PM characteristics:
      concentration, site, size fraction, oxidative potential and endotoxin content.
      RESULTS: Most PM samples induced a concentration-dependent decrease in MTT
      reduction activity and an increase in pro-inflammatory markers with the exception
      of the urban background and stop & go traffic samples. Fine and qUF samples of
      traffic locations, characterized by a high concentration of elemental and organic
      carbon, induced the highest pro-inflammatory activity. The pro-inflammatory
      response to coarse samples was associated with the endotoxin level, which was
      found to increase dramatically during a three-day sample concentration procedure
      in the laboratory. The underground samples, characterized by a high content of
      transition metals, showed the largest decrease in MTT-reduction activity. PM size
      fraction was not related to MTT-reduction activity, whereas there was a
      statistically significant difference in pro-inflammatory activity between Fine
      and qUF PM. Furthermore, there was a statistically significant negative
      association between PM oxidative potential and MTT-reduction activity.
      CONCLUSION: The response of RAW264.7 cells to ambient PM was markedly different
      using samples collected at various sites in the Netherlands that differed in
      their local PM emission sources. Our results are in support of other
      investigations showing that the chemical composition as well as oxidative
      potential are determinants of PM induced toxicity in vitro.

PMID- 21888646
TI  - MHC polymorphism and disease resistance to Vibrio anguillarum in 8 families of
      half-smooth tongue sole (Cynoglossus semilaevis).
AB  - BACKGROUND: Genes in the major histocompatibility complex (MHC) have a critical
      role in both the innate and adaptive immune responses because of their
      involvement in presenting foreign peptides to T cells. However, the nature has
      remained largely unknown. RESULTS: We examined the genetic variation in MHC class
      IIB in half-smooth tongue sole (Cynoglossus semilaevis) after challenge with
      vibrio anguillarum. Two thousand and four hundred fry from 12 half-smooth tongue
      sole families were challenged with Vibrio anguillarum. To determine any
      association between alleles and resistance or susceptibility to V. anguillarum,
      160 individuals from four high-resistance (HR, < 40.55% mortality) families and
      four low-resistance (LR, > 73.27% mortality) families were selected for MHC IIB
      exon2 gene sequence analysis. The MHC IIB exon2 genes of tongue sole displayed a
      high level of polymorphism and were discovered at least four loci. Meanwhile, the
      dN/dS [the ratio of non-synonymous (dN) substitutions to synonymous (dS)
      substitutions] in the peptide-binding region (PBR) was higher than that in the
      non-peptide-binding region (non-PBR). Eighty-eight alleles were discovered among
      160 individuals, and 13 out of 88 alleles were used to analyze the distribution
      pattern between the resistant and susceptible families. Certain alleles presented
      in HR and LR with a different frequency, while other alleles were discovered in
      only the HR or LR families, not both. Five alleles, Cyse-DBB*6501, Cyse-DBB*4002,
      Cyse-DBB*6102, Cyse-DBB*5601 and Cyse-DBB*2801, were found to be associated with
      susceptibility to V. anguillarum with a frequency of 1.25%, 1.25%, 1.25%, 1.25%
      and 2.5% in the HR families, and 35%, 33.75%, 27.5%, 16.25%, 15% in the LR
      families (p < 0.01, 0.01, 0.01, 0.01, 0.01), respectively. Four alleles, Cyse
      DBB*3301, Cyse-DBB*4701, Cyse-DBB*6801 and Cyse-DBB*5901, were found to be
      associated with resistance to V. anguillarum, with a frequency of 13.75%, 11.25%,
      11.25%, 8.75% in the HR families and 1.25%, 1.25%, 1.25%, 1.25% and 1.25% in the
      LR families (p < 0.01, 0.05, 0.05 and p = 0.064), respectively. CONCLUSIONS:
      Elucidation of the role of MHC II B genes in half-smooth tongue sole should prove
      to be helpful to the in-depth development of marker-assisted selective breeding
      in half-smooth tongue sole.

PMID- 21888647
TI  - Uranium and other contaminants in hair from the parents of children with
      congenital anomalies in Fallujah, Iraq.
AB  - BACKGROUND: Recent reports have drawn attention to increases in congenital birth
      anomalies and cancer in Fallujah Iraq blamed on teratogenic, genetic and genomic
      stress thought to result from depleted Uranium contamination following the
      battles in the town in 2004. Contamination of the parents of the children and of
      the environment by Uranium and other elements was investigated using Inductively
      Coupled Plasma Mass Spectrometry. Hair samples from 25 fathers and mothers of
      children diagnosed with congenital anomalies were analysed for Uranium and 51
      other elements. Mean ages of the parents was: fathers 29.6 (SD 6.2); mothers:
      27.3 (SD 6.8). For a sub-group of 6 women, long locks of hair were analysed for
      Uranium along the length of the hair to obtain information about historic
      exposures. Samples of soil and water were also analysed and Uranium isotope
      ratios determined. RESULTS: Levels of Ca, Mg, Co, Fe, Mn, V, Zn, Sr, Al, Ba, Bi,
      Ga, Pb, Hg, Pd and U (for mothers only) were significantly higher than published
      mean levels in an uncontaminated population in Sweden. In high excess were Ca,
      Mg, Sr, Al, Bi and Hg. Of these only Hg can be considered as a possible cause of
      congenital anomaly. Mean levels for Uranium were 0.16 ppm (SD: 0.11) range 0.02
      to 0.4, higher in mothers (0.18 ppm SD 0.09) than fathers (0.11 ppm; SD 0.13).
      The highly unusual non-normal Fallujah distribution mean was significantly higher
      than literature results for a control population Southern Israel (0.062 ppm) and
      a non-parametric test (Mann Whitney-Wilcoxon) gave p = 0.016 for this comparison
      of the distribution. Mean levels in Fallujah were also much higher than the mean
      of measurements reported from Japan, Brazil, Sweden and Slovenia (0.04 ppm SD
      0.02). Soil samples show low concentrations with a mean of 0.76 ppm (SD 0.42) and
      range 0.1-1.5 ppm; (N = 18). However it may be consistent with levels in drinking
      water (2.28 MUgL-1) which had similar levels to water from wells (2.72 MUgL-1)
      and the river Euphrates (2.24 MUgL-1). In a separate study of a sub group of
      mothers with long hair to investigate historic Uranium excretion the results
      suggested that levels were much higher in the past. Uranium traces detected in
      the soil samples and the hair showed slightly enriched isotopic signatures for
      hair U238/U235 = (135.16 SD 1.45) compared with the natural ratio of 137.88. Soil
      sample Uranium isotope ratios were determined after extraction and concentration
      of the Uranium by ion exchange. Results showed statistically significant presence
      of enriched Uranium with a mean of 129 with SD5.9 (for this determination, the
      natural Uranium 95% CI was 132.1 < Ratio < 144.1). CONCLUSIONS: Whilst caution
      must be exercised about ruling out other possibilities, because none of the
      elements found in excess are reported to cause congenital diseases and cancer
      except Uranium, these findings suggest the enriched Uranium exposure is either a
      primary cause or related to the cause of the congenital anomaly and cancer
      increases. Questions are thus raised about the characteristics and composition of
      weapons now being deployed in modern battlefields.

PMID- 21888648
TI  - Re-evaluating a vision-related quality of life questionnaire with item response
      theory (IRT) and differential item functioning (DIF) analyses.
AB  - BACKGROUND: For the Low Vision Quality Of Life questionnaire (LVQOL) it is
      unknown whether the psychometric properties are satisfactory when an item
      response theory (IRT) perspective is considered. This study evaluates some
      essential psychometric properties of the LVQOL questionnaire in an IRT model, and
      investigates differential item functioning (DIF). METHODS: Cross-sectional data
      were used from an observational study among visually-impaired patients (n = 296).
      Calibration was performed for every dimension of the LVQOL in the graded response
      model. Item goodness-of-fit was assessed with the S-X(2)-test. DIF was assessed
      on relevant background variables (i.e. age, gender, visual acuity, eye condition,
      rehabilitation type and administration type) with likelihood-ratio tests for DIF.
      The magnitude of DIF was interpreted by assessing the largest difference in
      expected scores between subgroups. Measurement precision was assessed by
      presenting test information curves; reliability with the index of subject
      separation. RESULTS: All items of the LVQOL dimensions fitted the model. There
      was significant DIF on several items. For two items the maximum difference
      between expected scores exceeded one point, and DIF was found on multiple
      relevant background variables. Item 1 'Vision in general' from the "Adjustment"
      dimension and item 24 'Using tools' from the "Reading and fine work" dimension
      were removed. Test information was highest for the "Reading and fine work"
      dimension. Indices for subject separation ranged from 0.83 to 0.94. CONCLUSIONS:
      The items of the LVQOL showed satisfactory item fit to the graded response model;
      however, two items were removed because of DIF. The adapted LVQOL with 21 items
      is DIF-free and therefore seems highly appropriate for use in heterogeneous
      populations of visually impaired patients.

PMID- 21888649
TI  - Rapid PCR detection of group A Streptococcus from flocked throat swabs: a
      retrospective clinical study.
AB  - BACKGROUND: Rapid diagnosis of GAS pharyngitis may improve patient care by
      ensuring that patients with GAS pharyngitis are treated quickly and also avoiding
      unnecessary use of antibiotics in those without GAS infection. Very few molecular
      methods for detection of GAS in clinical throat swab specimens have been
      described. METHODS: We performed a study of a laboratory-developed internally
      controlled rapid Group A streptococcus (GAS) PCR assay using flocked swab throat
      specimens. We compared the GAS PCR assay to GAS culture results using a
      collection of archived throat swab samples obtained during a study comparing the
      performance of conventional and flocked throat swabs. RESULTS: The sensitivity of
      the GAS PCR assay as compared to the reference standard was 96.0% (95% CI 90.1%
      to 98.4%), specificity 98.6% (95% CI 95.8% to 99.5%), positive predictive value
      (PPV) 96.9% (95% CI 91.4% to 99.0%) and negative predictive value (NPV) of 98.1%
      (95% CI 95.2% to 99.2%). For conventional swab cultures, sensitivity was 96.0%
      (95% CI 90.1% to 98.4%), specificity 100% (95% CI 98.2% to 100%), PPV 100%, (95%
      CI 96.1% to 100%) and NPV 98.1% (95% CI 95.2% to 99.3%) CONCLUSIONS: In this
      retrospective study, the GAS PCR assay appeared to perform as well as
      conventional throat swab culture, the current standard of practice. Since the GAS
      PCR assay, including DNA extraction, can be performed in approximately 1 hour,
      prospective studies of this assay are warranted to evaluate the clinical impact
      of the assay on management of patients with pharyngitis.

PMID- 21888652
TI  - Prevalence of dysglycemia among coronary artery bypass surgery patients with no
      previous diabetic history.
AB  - BACKGROUND: Dysglycemia is a major risk factor for atherosclerosis. In many
      patient populations dysglycemia is under-diagnosed. Patients with severe coronary
      artery disease commonly have dysglycemia and there is growing evidence that
      dysglycemia, irrespective of underlying history of diabetes, is associated with
      adverse outcome in coronary artery bypass graft (CABG) surgery patients,
      including longer hospital stay, wound infections, and higher mortality. As HbA1c
      is an easy and reliable way of checking for dysglycemia we routinely screen all
      patients undergoing CABG for elevations in HbA1c. Our hypothesis was that a
      substantial number of patients with dysglycemia that could be identified at the
      time of cardiothoracic surgery despite having no apparent history of diabetes.
      METHODS: 1045 consecutive patients undergoing CABG between 2007 and 2009 had
      HbA1c measured pre-operatively. The 2010 American Diabetes Association (ADA)
      diagnostic guidelines were used to categorize patients with no known history of
      diabetes as having diabetes (HbA1c >= 6.5%) or increased risk for diabetes (HbA1c
      5.7-6.4%). RESULTS: Of the 1045 patients with pre-operative HbA1c measurements,
      40% (n = 415) had a known history of diabetes and 60% (n = 630) had no known
      history of diabetes. For the 630 patients with no known diabetic history: 207
      (32.9%) had a normal HbA1c (< 5.7%); 356 (56.5%) had an HbA1c falling in the
      increased risk for diabetes range (5.7-6.4%); and 67 (10.6%) had an HbA1c in the
      diabetes range (6.5% or higher). In this study the only conventional risk factor
      that was predictive of high HbA1c was BMI. We also found a high HbA1c
      irrespective of history of DM was associated with severe coronary artery disease
      as indicated by the number of vessels revascularized. CONCLUSION: Among
      individuals undergoing CABG with no known history of diabetes, there is a
      substantial amount of undiagnosed dysglycemia. Even though labeling these
      patients as "diabetic" or "increased risk for diabetes" remains controversial in
      terms of perioperative management, pre-operative screening could lead to
      appropriate post-operative follow up to mitigate short-term adverse outcome and
      provide high priority medical referrals of this at risk population.

PMID- 21888650
TI  - Antimicrobial peptides and proteins of the horse--insights into a well-armed
      organism.
AB  - Antimicrobial peptides play a pivotal role as key effectors of the innate immune
      system in plants and animals and act as endogenous antibiotics. The molecules
      exhibit an antimicrobial activity against bacteria, viruses, and eukaryotic
      pathogens with different specificities and potencies depending on the structure
      and amino-acid composition of the peptides. Several antimicrobial peptides were
      comprehensively investigated in the last three decades and some molecules with
      remarkable antimicrobial properties have reached the third phase of clinical
      studies. Next to the peptides themselves, numerous organisms were examined and
      analyzed regarding their repertoire of antimicrobial peptides revealing a huge
      number of candidates with potencies and properties for future medical
      applications. One of these organisms is the horse, which possesses numerous
      peptides that are interesting candidates for therapeutical applications in
      veterinary medicine. Here we summarize investigations and knowledge on equine
      antimicrobial peptides, point to interesting candidates, and discuss prospects
      for therapeutical applications.

PMID- 21888651
TI  - Cellular kinases incorporated into HIV-1 particles: passive or active passengers?
AB  - Phosphorylation is one of the major mechanisms by which the activities of protein
      factors can be regulated. Such regulation impacts multiple key-functions of
      mammalian cells, including signal transduction, nucleo-cytoplasmic shuttling,
      macromolecular complexes assembly, DNA binding and regulation of enzymatic
      activities to name a few. To ensure their capacities to replicate and propagate
      efficiently in their hosts, viruses may rely on the phosphorylation of viral
      proteins to assist diverse steps of their life cycle. It has been known for
      several decades that particles from diverse virus families contain some protein
      kinase activity. While large DNA viruses generally encode for viral kinases, RNA
      viruses and more precisely retroviruses have acquired the capacity to hijack the
      signaling machinery of the host cell and to embark cellular kinases when budding.
      Such property was demonstrated for HIV-1 more than a decade ago. This review
      summarizes the knowledge acquired in the field of HIV-1-associated kinases and
      discusses their possible function in the retroviral life cycle.

PMID- 21888653
TI  - Suspected idiopathic sclerosing orbital inflammation presenting as immunoglobulin
      G4-related disease: a case report.
AB  - INTRODUCTION: Idiopathic sclerosing orbital inflammation is a rare and ill
      defined heterogeneous entity, and a distinct subset of orbital inflammation.
      Recently, attention has been focused on immunoglobulin G4-related disease
      complicated with fibrotic changes in some other organs with high serum
      immunoglobulin G4 levels. This report presents a case of suspected idiopathic
      sclerosing orbital inflammation complicated with high serum immunoglobulin G4
      levels. CASE PRESENTATION: An 82-year-old Japanese woman had a 30-year history of
      chronic thyroiditis. She experienced right ptosis and eyelid swelling. These
      symptoms gradually developed over five years. The clinical and radiographic
      findings suggested that our patient had idiopathic sclerosing orbital
      inflammation. We were unable to obtain our patient's consent to perform a biopsy.
      While the serum immunoglobulin G level was within the normal limits, the serum
      immunoglobulin G4 level was significantly elevated. The serum immunoglobulin G4
      levels decreased after the administration of oral prednisolone at a daily dose of
      20 mg. In addition, the swelling and ptosis of the right upper eyelid disappeared
      gradually after four weeks. Our patient was then suspected to have idiopathic
      sclerosing orbital inflammation complicated with immunoglobulin G4-related
      disease and chronic thyroiditis. CONCLUSION: An orbital pseudotumor of this type
      is indicative of idiopathic sclerosing orbital inflammation immunoglobulin G4
      related disease. Immunoglobulin G4 may thus be considered a subclass of
      immunoglobulin G when the serum immunoglobulin G level is within normal limits.

PMID- 21888654
TI  - Transcriptomic analysis of the zebrafish inner ear points to growth hormone
      mediated regeneration following acoustic trauma.
AB  - BACKGROUND: Unlike mammals, teleost fishes are capable of regenerating sensory
      inner ear hair cells that have been lost following acoustic or ototoxic trauma.
      Previous work indicated that immediately following sound exposure, zebrafish
      saccules exhibit significant hair cell loss that recovers to pre-treatment levels
      within 14 days. Following acoustic trauma in the zebrafish inner ear, we used
      microarray analysis to identify genes involved in inner ear repair following
      acoustic exposure. Additionally, we investigated the effect of growth hormone
      (GH) on cell proliferation in control zebrafish utricles and saccules, since GH
      was significantly up-regulated following acoustic trauma. RESULTS: Microarray
      analysis, validated with the aid of quantitative real-time PCR, revealed several
      genes that were highly regulated during the process of regeneration in the
      zebrafish inner ear. Genes that had fold changes of >= 1.4 and P -values <= 0.05
      were considered significantly regulated and were used for subsequent analysis.
      Categories of biological function that were significantly regulated included
      cancer, cellular growth and proliferation, and inflammation. Of particular
      significance, a greater than 64-fold increase in growth hormone (gh1) transcripts
      occurred, peaking at 2 days post-sound exposure (dpse) and decreasing to
      approximately 5.5-fold by 4 dpse. Pathway Analysis software was used to reveal
      networks of regulated genes and showed how GH affected these networks. Subsequent
      experiments showed that intraperitoneal injection of salmon growth hormone
      significantly increased cell proliferation in the zebrafish inner ear. Many other
      gene transcripts were also differentially regulated, including heavy and light
      chain myosin transcripts, both of which were down-regulated following sound
      exposure, and major histocompatability class I and II genes, several of which
      were significantly regulated on 2 dpse. CONCLUSIONS: Transcripts for GH, MHC
      Class I and II genes, and heavy- and light-chain myosins, as well as many others
      genes, were differentially regulated in the zebrafish inner ear following
      overexposure to sound. GH injection increased cell proliferation in the inner ear
      of non-sound-exposed zebrafish, suggesting that GH could play an important role
      in sensory hair cell regeneration in the teleost ear.

PMID- 21888655
TI  - Sentinel lymph node biopsy is unsuitable for routine practice in younger female
      patients with unilateral low-risk papillary thyroid carcinoma.
AB  - BACKGROUND: Sentinel lymph node (SLN) biopsy has been used to assess patients
      with papillary thyroid carcinoma (PTC). To achieve its full potential the rate of
      SLN identification must be as close to 100 percent as possible. In the present
      study we compared the combination of preoperative lymphoscintigraphy scanning by
      sulfur colloid labeled with 99 m Technetium, gamma-probe guided surgery, and
      methylene blue with methylene blue, alone, for sentinel node identification in
      younger women with unilateral low-risk PTC. METHODS: From January 2004 to January
      2007, 90 female patients, ages 23 to 44 (mean = 35), with unilateral low-risk PTC
      (T1-2N0M0) were prospectively studied. Mean tumor size was 1.3 cm (range, 0.8-3.7
      cm). All patients underwent unilateral modified neck dissection. Prior to
      surgery, patients had, by random assignment, identification and biopsy of SLNs by
      methylene blue, alone (Group 1), or by sulfur colloid labeled with 99 m
      Technetium, gamma-probe guided surgery and methylene blue (Group 2). RESULTS: In
      the methylene blue group, SLNs were identified in 39 of 45 patients (86.7%). Of
      the 39 patients, 28 (71.8%) had positive cervical lymph nodes (pN+), and 21
      patients (53.8%) had pSLN+. In 7 of the 28 pN+ patients (25%), metastases were
      also detected in non-SLN, thus giving a false-negative rate (FNR of 38.9% (7/18),
      a negative predictive value (NPV) of 61.1% (11/18), and an accuracy of 82.1%
      (32/39). In the combined technique group, the identification rate (IR) of SLN was
      100% (45/45). Of the 45 patients, 27 (60.0%) had pN+, 24 (53.3%) had pSLN+. There
      was a FNR of 14.3% (3/21), a NPV of 85.7% (18/21), and an accuracy of 93.3%
      (42/45). The combined techniques group was significantly superior to the
      methylene blue group in IR (p = 0.035). There were no significant differences
      between two groups in sensitivity, specificity, NPV, or accuracy. Location of pN+
      (55 patients) in 84 patients was: level I and V, no patients; level II, 1 patient
      (1.2%); level III, 6 patients (7.2%); level III and IV, 8 patients (9.5%); level
      IV, alone, 8 patients (9.5%); level VI, 32 patients (38.1%). In all 90 patients,
      IR of SLN was 93.3%, FNR, 25.6%, NPV, 74.4%, and accuracy rate, 88.1 percent.
      CONCLUSIONS: Compared to a single technique, there was a significantly higher SLN
      identification rate for the combined technique in younger female with
      ipsilateral, low-risk PTC (T1-2N0M0). Thus, a combined SLN biopsy technique seems
      to more accurately stage lymph nodes, with better identification of SLN located
      out of the central compartment. Regardless of the procedure used, the high FNR
      renders the current SLN techniques unsuitable for routine practice. Based on
      these results, prophylactic node dissection of level VI might be considered
      because 38.1% of our patients had such node metastases.

PMID- 21888657
TI  - Visual error augmentation enhances learning in three dimensions.
AB  - Because recent preliminary evidence points to the use of Error augmentation (EA)
      for motor learning enhancements, we visually enhanced deviations from a straight
      line path while subjects practiced a sensorimotor reversal task, similar to
      laparoscopic surgery. Our study asked 10 healthy subjects in two groups to
      perform targeted reaching in a simulated virtual reality environment, where the
      transformation of the hand position matrix was a complete reversal--rotated 180
      degrees about an arbitrary axis (hence 2 of the 3 coordinates are reversed). Our
      data showed that after 500 practice trials, error-augmented-trained subjects
      reached the desired targets more quickly and with lower error (differences of 0.4
      seconds and 0.5 cm Maximum Perpendicular Trajectory deviation) when compared to
      the control group. Furthermore, the manner in which subjects practiced was
      influenced by the error augmentation, resulting in more continuous motions for
      this group and smaller errors. Even with the extreme sensory discordance of a
      reversal, these data further support that distorted reality can promote more
      complete adaptation/learning when compared to regular training. Lastly, upon
      removing the flip all subjects quickly returned to baseline rapidly within 6
      trials.

PMID- 21888656
TI  - Effect of praziquantel treatment of Schistosoma mansoni during pregnancy on
      immune responses to schistosome antigens among the offspring: results of a
      randomised, placebo-controlled trial.
AB  - BACKGROUND: Offspring of women with schistosomiasis may exhibit immune
      responsiveness to schistosomes due to in utero sensitisation or trans-placental
      transfer of antibodies. Praziquantel treatment during pregnancy boosts maternal
      immune responses to schistosome antigens and reduces worm burden. Effects of
      praziquantel treatment during pregnancy on responses among offspring are unknown.
      METHODS: In a trial of anthelminthic treatment during pregnancy in Uganda
      (ISRCTN32849447; http://www.controlled-trials.com/ISRCTN32849447/elliott),
      offspring of women with Schistosoma mansoni were examined for cytokine and
      antibody responses to schistosome worm (SWA) and egg (SEA) antigen, in cord blood
      and at age one year. Relationships to maternal responses and pre-treatment
      infection intensities were examined, and responses were compared between the
      offspring of women who did, or did not receive praziquantel treatment during
      pregnancy. RESULTS: Of 388 S. mansoni-infected women studied, samples were
      obtained at age one year from 215 of their infants. Stool examination for S.
      mansoni eggs was negative for all infants. Cord and infant samples were
      characterised by very low cytokine production in response to schistosome antigens
      with the exception of cord IL-10 responses, which were substantial. Cord and
      infant cytokine responses showed no association with maternal responses. As
      expected, cord blood levels of immunoglobulin (Ig) G to SWA and SEA were high and
      correlated with maternal antibodies. However, by age one year IgG levels had
      waned and were hardly detectable. Praziquantel treatment during pregnancy showed
      no effect on cytokine responses or antibodies levels to SWA or SEA either in cord
      blood or at age one year, except for IgG1 to SWA, which was elevated in infants
      of treated mothers, reflecting maternal levels. There was some evidence that
      maternal infection intensity was positively associated with cord blood IL-5 and
      IL-13 responses to SWA, and IL-5 responses to SEA, and that this association was
      modified by treatment with praziquantel. CONCLUSIONS: Despite strong effects on
      maternal infection intensity and maternal immune responses, praziquantel
      treatment of infected women during pregnancy had no effect on anti-schistosome
      immune responses among offspring by age one year. Whether the treatment will
      impact upon the offspring's responses on exposure to primary schistosome
      infection remains to be elucidated. TRIAL REGISTRATION: ISRCTN: ISRCTN32849447.

PMID- 21888658
TI  - Preferential expression of potential markers for cancer stem cells in large cell
      neuroendocrine carcinoma of the lung. An FFPE proteomic study.
AB  - BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) of the lung, a subtype of
      large cell carcinoma (LCC), is characterized by neuroendocrine differentiation
      that small cell lung carcinoma (SCLC) shares. Pre-therapeutic histological
      distinction between LCNEC and SCLC has so far been problematic, leading to
      adverse clinical outcome. We started a project establishing protein targets
      characteristic of LCNEC with a proteomic method using formalin fixed paraffin
      embedded (FFPE) tissues, which will help make diagnosis convincing. METHODS:
      Cancer cells were collected by laser microdissection from cancer foci in FFPE
      tissues of LCNEC (n = 4), SCLC (n = 5), and LCC (n = 5) with definite
      histological diagnosis. Proteins were extracted from the harvested sections,
      trypsin-digested, and subjected to HPLC/mass spectrometry. Proteins identified by
      database search were semi-quantified by spectral counting and statistically
      sorted by pair-wise G-statistics. The results were immunohistochemically verified
      using a total of 10 cases for each group to confirm proteomic results. RESULTS: A
      total of 1981 proteins identified from the three cancer groups were subjected to
      pair-wise G-test under p < 0.05 and specificity of a protein's expression to
      LCNEC was checked using a 3D plot with the coordinates comprising G-statistic
      values for every two group comparisons. We identified four protein candidates
      preferentially expressed in LCNEC compared with SCLC with convincingly low p
      values: aldehyde dehydrogenase 1 family member A1 (AL1A1) (p = 6.1 * 10-4), aldo
      keto reductase family 1 members C1 (AK1C1) (p = 9.6x10-10) and C3 (AK1C3) (p =
      3.9x10-10) and CD44 antigen (p = 0.021). These p-values were confirmed by non
      parametric exact inference tests. Interestingly, all these candidates would
      belong to cancer stem cell markers. Immunohistochmistry supported proteomic
      results. CONCLUSIONS: These results suggest that candidate biomarkers of LCNEC
      were related to cancer stem cells and this proteomic approach via FFPE samples
      was effective to detect them.

PMID- 21888659
TI  - Efficient activation of T cells by human monocyte-derived dendritic cells (HMDCs)
      pulsed with Coxiella burnetii outer membrane protein Com1 but not by HspB-pulsed
      HMDCs.
AB  - BACKGROUND: Coxiella burnetii is an obligate intracellular bacterium and the
      etiologic agent of Q fever; both coxiella outer membrane protein 1 (Com1) and
      heat shock protein B (HspB) are its major immunodominant antigens. It is not
      clear whether Com1 and HspB have the ability to mount immune responses against C.
      burnetii infection. RESULTS: The recombinant proteins Com1 and HspB were applied
      to pulse human monocyte-derived dendritic cells (HMDCs), and the pulsed HMDCs
      were used to stimulate isogenic T cells. Com1-pulsed HMDCs expressed
      substantially higher levels of surface molecules (CD83, CD40, CD80, CD86, CD54,
      and CD58) and a higher level of interleukin-12 than HspB-pulsed HMDCs. Moreover,
      Com1-pulsed HMDCs induced high-level proliferation and activation of CD4(+) and
      CD8(+) cells, which expressed high levels of T-cell activation marker CD69 and
      inflammatory cytokines IFN-gamma and TNF-alpha. In contrast, HspB-pulsed HMDCs
      were unable to induce efficient T-cell proliferation and activation. CONCLUSIONS:
      Our results demonstrate that Com1-pulsed HMDCs are able to induce efficient T
      cell proliferation and drive T cells toward Th1 and Tc1 polarization; however,
      HspB-pulsed HMDCs are unable to do so. Unlike HspB, Com1 is a protective antigen,
      which was demonstrated by the adoptive transfer of Com1-pulsed bone marrow
      dendritic cells into naive BALB/c mice.

PMID- 21888660
TI  - Helping hands: a cluster randomised trial to evaluate the effectiveness of two
      different strategies for promoting hand hygiene in hospital nurses.
AB  - BACKGROUND: Hand hygiene prescriptions are the most important measure in the
      prevention of hospital-acquired infections. Yet, compliance rates are generally
      below 50% of all opportunities for hand hygiene. This study aims at evaluating
      the short- and long-term effects of two different strategies for promoting hand
      hygiene in hospital nurses. METHODS/DESIGN: This study is a cluster randomised
      controlled trial with inpatient wards as the unit of randomisation. Guidelines
      for hand hygiene will be implemented in this study. Two strategies will be used
      to improve the adherence to guidelines for hand hygiene. The state-of-the-art
      strategy is derived from the literature and includes education, reminders,
      feedback, and targeting adequate products and facilities. The extended strategy
      also contains activities aimed at influencing social influence in groups and
      enhancing leadership. The unique contribution of the extended strategy is built
      upon relevant behavioural science theories. The extended strategy includes all
      elements of the state-of-the-art strategy supplemented with gaining active
      commitment and initiative of ward management, modelling by informal leaders at
      the ward, and setting norms and targets within the team. Data will be collected
      at four points in time, with six-month intervals. An average of 3,000
      opportunities for hand hygiene in approximately 900 nurses will be observed at
      each time point. DISCUSSION: Performing and evaluating an implementation strategy
      that also targets the social context of teams may considerably add to the general
      body of knowledge in this field. Results from our study will allow us to draw
      conclusions on the effects of different strategies for the implementation of hand
      hygiene guidelines, and based on these results we will be able to define a
      preferred implementation strategy for hospital based nursing. TRIAL REGISTRATION:
      The study is registered as a Clinical Trial in ClinicalTrials.gov, dossier
      number: NCT00548015.

PMID- 21888661
TI  - Differential expression of proteins and phosphoproteins during larval
      metamorphosis of the polychaete Capitella sp. I.
AB  - BACKGROUND: The spontaneous metamorphosis of the polychaete Capitella sp. I
      larvae into juveniles requires minor morphological changes, including segment
      formation, body elongation, and loss of cilia. In this study, we investigated
      changes in the expression patterns of both proteins and phosphoproteins during
      the transition from larvae to juveniles in this species. We used two-dimensional
      gel electrophoresis (2-DE) followed by multiplex fluorescent staining and MALDI
      TOF mass spectrometry analysis to identify the differentially expressed proteins
      as well as the protein and phosphoprotein profiles of both competent larvae and
      juveniles. RESULTS: Twenty-three differentially expressed proteins were
      identified in the two developmental stages. Expression patterns of two of those
      proteins were examined at the protein level by Western blot analysis while seven
      were further studied at the mRNA level by real-time PCR. Results showed that
      proteins related to cell division, cell migration, energy storage and oxidative
      stress were plentifully expressed in the competent larvae; in contrast, proteins
      involved in oxidative metabolism and transcriptional regulation were abundantly
      expressed in the juveniles. CONCLUSION: It is likely that these differentially
      expressed proteins are involved in regulating the larval metamorphosis process
      and can be used as protein markers for studying molecular mechanisms associated
      with larval metamorphosis in polychaetes.

PMID- 21888662
TI  - Genotyping analysis of Helicobacter pylori using multiple-locus variable-number
      tandem-repeats analysis in five regions of China and Japan.
AB  - BACKGROUND: H. pylori (Helicobacter pylori) is the major causative agent of
      chronic active gastritis. The population of H. pylori shows a high genomic
      variability among isolates. And the polymorphism of repeat-units of genomics had
      participated the important process of evolution. Its long term colonization of
      the stomach caused different clinical outcomes, which may relate to the high
      degree of genetic variation of H. pylori. A variety of molecular typing tools
      have been developed to access genetic relatedness in H. pylori isolates. However,
      there is still no standard genotyping system of this bacterium. The MLVA (Multi
      locus of variable number of tandem repeat analysis) method is useful for
      performing phylogenetic analysis and is widely used in bacteria genotyping;
      however, there's little application in H. pylori analysis. This article is the
      first application of the MLVA method to investigate H. pylori from different
      districts and ethnic groups of China. RESULTS: MLVA of 12 VNTR loci with high
      discrimination power based on 30 candidates were performed on a collection of 202
      strains of H. pylori which originated from five regions of China and Japan.
      Phylogenetic tree was constructed using MLVA profiles. 12 VNTR loci presented
      with high various polymorphisms, and the results demonstrated very close
      relationships between genotypes and ethnic groups. CONCLUSIONS: This study used
      MLVA methodology providing a new perspective on the ethnic groups and
      distribution characteristics of H. pylori.

PMID- 21888663
TI  - Cyclin D1 expression in colorectal cancer is a favorable prognostic factor in men
      but not in women in a prospective, population-based cohort study.
AB  - BACKGROUND: Although colorectal cancer (CRC) is generally not considered to be a
      hormone-dependent malignancy, several sex-related differences in incidence,
      molecular characteristics and survival have been reported. Epidemiological
      studies have consistently shown that increased exposure to female sex hormones is
      associated with a lower risk of CRC in women, and cyclin D1, an important
      downstream effector in estrogen-mediated signaling, is commonly activated in CRC.
      In this study, we analyzed the prognostic significance of cyclin D1 expression in
      CRC, with particular reference to sex-related differences, in tumors from a
      large, prospective, population-based cohort. METHODS: Using tissue microarrays
      and immunohistochemistry, the fraction and intensity of cyclin D1 expression was
      evaluated in 527 incident CRC cases from the Malmo Diet and Cancer Study. The
      chi2 and Spearman's rho (rho) tests were used for comparison of cyclin D1
      expression and relevant clinicopathological characteristics. Kaplan-Meier
      analysis and Cox proportional hazards modeling were used to assess the effect of
      cyclin D1 expression on cancer-specific survival (CSS) in univariate and
      multivariate analysis, adjusted for established prognostic factors. RESULTS:
      Cyclin D1 intensity was significantly lower in male compared with female CRC (P =
      0.018). In the full cohort, cyclin D1 expression was associated with a
      significantly prolonged CSS (hazard ratio (HR) = 0.69; 95% CI 0.49 to 0.96, P =
      0.026) but subgroup analysis according to gender revealed a strongly accentuated
      prognostic effect of cyclin D1 in male CRC (HR = 0.48; 95% CI 0.31 to 0.74, P <
      0.001), which was in contrast to female CRC, where cyclin D1 was not prognostic
      (HR = 1.05; 95% CI 0.62 to 1.78, P = 0.864) (Pinteraction = 0.024). The
      prognostic value of cyclin D1 was not retained in multivariate analysis, either
      in the full cohort or in male CRC. CONCLUSIONS: Cyclin D1 expression is strongly
      associated with prolonged survival in male CRC. These findings not only support
      an important role for cyclin D1 in colorectal carcinogenesis, but also add
      further weight to the accumulating evidence that CRC is indeed a hormone
      dependent malignancy, for which prognostic and treatment-predictive molecular
      biomarkers should be evaluated differently in women and men.

PMID- 21888664
TI  - Comparison between observed children's tooth brushing habits and those reported
      by mothers.
AB  - BACKGROUND: Information bias can occur in epidemiological studies and compromise
      scientific outcomes, especially when evaluating information given by a patient
      regarding their own health. The oral habits of children reported by their mothers
      are commonly used to evaluate tooth brushing practices and to estimate fluoride
      intake by children. The aim of the present study was to compare observed tooth
      brushing habits of young children using fluoridated toothpaste with those
      reported by mothers. METHODS: A sample of 201 mothers and their children (aged 24
      48 months) from Montes Claros, Brazil, took part in a cross-sectional study. At
      day-care centres, the mothers answered a self-administered questionnaire on their
      child's tooth-brushing habits. The structured questionnaire had six items with
      two to three possible answers. An appointment was then made with each
      mother/child pair at day-care centres. The participants were asked to demonstrate
      the tooth-brushing practice as usually performed at home. A trained examiner
      observed and documented the procedure. Observed tooth brushing and that reported
      by mothers were compared for overall agreement using Cohen's Kappa coefficient
      and the McNemar test. RESULTS: Cohen's Kappa values comparing mothers' reports
      and tooth brushing observed by the examiner ranged from poor-to-good (0.00-0.75).
      There were statistically significant differences between observed tooth brushing
      habits and those reported by mothers (p < 0.001). When observed by the examiner,
      the frequencies of dentifrice dispersed on all bristles (35.9%), children who
      brushed their teeth alone (33.8%) and those who did not rinse their mouths during
      brushing (42.0%) were higher than those reported by the mothers (12.1%, 18.9% and
      6.5%, respectively; p < 0.001). CONCLUSIONS: In general, there was low agreement
      between observed tooth brushing and mothers' reports. Moreover, the different
      methods of estimation resulted in differences in the frequencies of tooth
      brushing habits, indicative of reporting bias. Data regarding children's tooth
      brushing habits as reported by mothers should be considered with caution in
      epidemiological surveys on fluoridated dentifrice use and the risk of dental
      fluorosis.

PMID- 21888665
TI  - A decision aid for considering indomethacin prophylaxis vs. symptomatic treatment
      of PDA for extreme low birth weight infants.
AB  - BACKGROUND: Decision Aids (DA) are well established in various fields of
      medicine. It can improve the quality of decision-making and reduce decisional
      conflict. In neonatal care, and due to scientific equipoise, neonatologists
      caring for extreme low birth weight (ELBW) infants are in need to elicit parents'
      preferences with regard to the use of indomethacin therapy in ELBW infants. We
      aimed to develop a DA that elicits parents' preferences with regard to
      indomethacin therapy in ELBW infants. METHODS: We developed a DA for the use of
      the indomethacin therapy in ELBW infants according to the Ottawa Decision Support
      Framework. The development process involved parents, neonatologists, DA
      developers and decision making experts. A pilot testing with healthy volunteers
      was conducted through an evaluation questionnaire, a knowledge scale, and a
      validated decisional conflict scale. RESULTS: The DA is a computer-based
      interactive tool. In the first part, the DA provides information about patent
      ductus arteriosus (PDA) as a disease, the different treatment options, and the
      benefits and downsides of using indomethacin therapy in preterm infants. In the
      second part, it coaches the parent in the decision making process through
      clarifying values and preferences. Volunteers rated 10 out of 13 items of the DA
      positively and showed significant improvement on both the knowledge scale (p =
      0.008) and the decisional conflict scale (p = 0.008). CONCLUSION: We have
      developed a computer based DA to assess parental preferences with regard to
      indomethacin therapy in preterm infants. Future research will involve measurement
      of parental preferences to guide and augment the clinical decisions in current
      neonatal practice.

PMID- 21888666
TI  - HIV/AIDS among youth in urban informal (slum) settlements in Kenya: what are the
      correlates of and motivations for HIV testing?
AB  - BACKGROUND: Although HIV counseling and testing (HCT) is widely considered an
      integral component of HIV prevention and treatment strategies, few studies have
      examined HCT behavior among youth in sub-Saharan Africa-a group at substantial
      risk for HIV infection. In this paper we examine: the correlates of HIV testing,
      including whether associations differ based on the context under which a person
      gets tested; and the motivations for getting (or not getting) an HIV test.
      METHODS: Drawing on data collected in 2007 from 4028 (51% male) youth (12-22
      years) living in Korogocho and Viwandani slum settlements in Nairobi (Kenya), we
      explored the correlates of and motivations for HIV testing using the Health
      Belief Model (HBM) as a theoretical framework. Multinomial and binary logistic
      regression analyses were employed to examine correlates of HIV testing. Bivariate
      analyses were employed to assess reasons for or against testing. RESULTS:
      Nineteen percent of males and 35% of females had been tested. Among tested youth,
      74% of males and 43% of females had requested for their most recent HIV test
      while 7% of males and 32% of females reported that they were required to take
      their most recent HIV test (i.e., the test was mandatory). About 60% of females
      who had ever had sex received an HIV test because they were pregnant. We found
      modest support for the HBM in explaining variation in testing behavior. In
      particular, we found that perceived risk for HIV infection may drive HIV testing
      among youth. For example, about half of youth who had ever had sex but had never
      been tested reported that they had not been tested because they were not at risk.
      CONCLUSIONS: Targeted interventions to help young people correctly assess their
      level of risk and to increase awareness of the potential value of HIV testing may
      help enhance uptake of testing services. Given the relative success of Prevention
      of Mother-to-Child Transmission (PMTCT) services in increasing HIV testing rates
      among females, routine provider-initiated testing and counseling among all
      clients visiting medical facilities may provide an important avenue to increase
      HIV status awareness among the general population and especially among males.

PMID- 21888668
TI  - Ultrasonographic findings in a cow with vascular hamartoma of the liver: case
      report.
AB  - BACKGROUND: This is the first description of the ultrasonographic findings in a
      cow with vascular hamartoma of the liver. CASE PRESENTATION: Ultrasonographic
      examination of a six-year-old Swiss Braunvieh cow revealed an excessive number of
      hypoechogenic blood vessels in the liver parenchyma and a thrombus in the right
      hepatic vein. The activities of the liver enzymes and the concentration of
      bilirubin were within the reference ranges. At postmortem examination, a poorly
      delineated, non-encapsulated lesion, measuring approximately 10 cm * 10 cm in
      diameter, was found in the right liver lobe. The cut surface of the lesion was
      sponge-like and contained extremely dilated blood vessels, one of which was
      occluded with a branching red thrombus. A vascular hamartoma of the liver with
      thrombosis was diagnosed based on the histological findings. CONCLUSIONS: To our
      knowledge, this is the first description of the ultrasonographic findings of
      vascular hamartoma of the liver in a cow. Hamartoma should be considered part of
      the differential diagnosis in cows with an abnormally large number of blood
      vessels in the liver parenchyma. This case report broadens the spectrum of liver
      diseases and ultrasonographic findings of the liver in cattle.

PMID- 21888667
TI  - An overview on ELISA techniques for FMD.
AB  - BACKGROUND: FMD is one of the major causes of economic loss of cloven-hoofed
      animals in the world today. The assessment of dominant genotype/lineage and
      prevalent trends and confirmation the presence of infection or vaccination not
      only provides scientific basis and first-hand information for appropriate control
      measure but also for disease eradication and regaining FMD free status following
      an outbreak. Although different biological and serological approaches are still
      applied to study this disease, ELISA test based on the distinct format, antigen
      type and specific antibody reinforce its predominance in different research areas
      of FMD, and this may replace the traditional methods in the near future. This
      review gives comprehensive insight on ELISA currently available for typing,
      antigenic analysis, vaccination status differentiation and surveillance vaccine
      purity and content at all stages of manufacture in FMDV. Besides, some viewpoint
      about the recent advances and trends of ELISA reagent for FMD are described here.
      METHODS: More than 100 studies regarding ELISA method available for FMD
      diagnosis, antigenic analysis and monitor were thoroughly reviewed. We
      investigated previous sagacious results of these tests on their sensitivity,
      specificity. RESULTS: We found that in all ELISA formats for FMD, antibody
      trapping and competitive ELISAs have high specificity and RT-PCR (oligoprobing)
      ELISA has extra sensitivity. A panel of monoclonal antibodies to different sites
      or monoclonal antibody in combination of antiserum is the most suitable
      combination of antibodies in ELISA for FMD. Even though from its beginning, 3ABC
      is proven to be best performance in many studies, no single NSP can differentiate
      infected from vaccinated animals with complete confidence. Meanwhile, recombinant
      antigens and peptide derived from FMDV NPs, and NSPs have been developed for use
      as an alternative to the inactivated virus antigen for security. CONCLUSIONS:
      There is a need of target protein, which accurately determines the susceptible
      animal status based on the simple, fast and reliable routine laboratory test. A
      further alternative based on virus-like particle (VLP, also called empty capsids)
      in combination of high throughput antibody technique (Phage antibody
      library/antibody microarray) may be the powerful ELISA diagnostic reagents in
      future.

PMID- 21888670
TI  - With good intentions: complexity in unsolicited informal support for Aboriginal
      and Torres Strait Islander peoples. A qualitative study.
AB  - BACKGROUND: Understanding people's social lived experiences of chronic illness is
      fundamental to improving health service delivery and health outcomes,
      particularly in relation to self-management activity. In explorations of social
      lived experiences this paper uncovers the ways in which Aboriginal and Torres
      Strait Islander people with chronic illness experience informal unsolicited
      support from peers and family members. METHODS: Nineteen Aboriginal and Torres
      Islander participants were interviewed in the Serious and Continuing Illness
      Policy and Practice Study (SCIPPS). Participants were people with Type 2 diabetes
      (N = 17), chronic obstructive pulmonary disease (N = 3) and/or chronic heart
      failure (N = 11) and family carers (N = 3). Participants were asked to describe
      their experience of having or caring for someone with chronic illness. Content
      and thematic analysis of in-depth semi-structured interviews was undertaken,
      assisted by QSR Nvivo8 software. RESULTS: Participants reported receiving several
      forms of unsolicited support, including encouragement, practical suggestions for
      managing, nagging, growling, and surveillance. Additionally, participants had
      engaged in 'yarning', creating a 'yarn' space, the function of which was
      distinguished as another important form of unsolicited support. The implications
      of recognising these various support forms are discussed in relation to responses
      to unsolicited support as well as the needs of family carers in providing
      effective informal support. CONCLUSIONS: Certain locations of responsibility are
      anxiety producing. Family carers must be supported in appropriate education so
      that they can provide both solicited and unsolicited support in effective ways.
      Such educational support would have the added benefit of helping to reduce carer
      anxieties about caring roles and responsibilities. Mainstream health services
      would benefit from fostering environments that encourage informal interactions
      that facilitate learning and support in a relaxed atmosphere.

PMID- 21888669
TI  - Clamp-crushing versus stapler hepatectomy for transection of the parenchyma in
      elective hepatic resection (CRUNSH)--a randomized controlled trial (NCT01049607).
AB  - BACKGROUND: Hepatic resection is still associated with significant morbidity.
      Although the period of parenchymal transection presents a crucial step during the
      operation, uncertainty persists regarding the optimal technique of transection.
      It was the aim of the present randomized controlled trial to evaluate the
      efficacy and safety of hepatic resection using the technique of stapler
      hepatectomy compared to the simple clamp-crushing technique. METHODS/DESIGN: The
      CRUNSH Trial is a prospective randomized controlled single-center trial with a
      two-group parallel design. Patients scheduled for elective hepatic resection
      without extrahepatic resection at the Department of General-, Visceral- and
      Transplantation Surgery, University of Heidelberg are enrolled into the trial and
      randomized intraoperatively to hepatic resection by the clamp-crushing technique
      and stapler hepatectomy, respectively. The primary endpoint is total
      intraoperative blood loss. A set of general and surgical variables are documented
      as secondary endpoints. Patients and outcome-assessors are blinded for the
      treatment intervention. DISCUSSION: The CRUNSH Trial is the first randomized
      controlled trial to evaluate efficacy and safety of stapler hepatectomy compared
      to the clamp-crushing technique for parenchymal transection during elective
      hepatic resection. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01049607.

PMID- 21888671
TI  - True prevalence of twin HDV-HBV infection in Pakistan: a molecular approach.
AB  - Hepatitis Delta Virus (HDV) infects only patients that are already infected by
      hepatitis B virus (HBV) because this is sub satellite virus which depends on and
      propagate only in the presence of HBV. HDV causes co-infection or super infection
      with sever complication as compared to only HBV infection. No study on molecular
      level on HDV is available from this region; therefore, the aim of this study was
      to found out the molecular epidemiology of HDV (as a co-infection with HBV) in
      different geographical regions of Pakistan.Total 228 HBsAg positive samples were
      received for the study from different geographical regions of the country. Only
      HBV DNA PCR positive samples were further utilized for the presence of HDV RNA.
      For this purpose, HDV RNA and HBV DNA was extracted and amplified using reverse
      transcriptase polymerase chain reaction (RT-PCR), nested PCR and real-time PCR.
      Out of the total 228 HBsAg positive samples, HBV DNA was detected in total 190
      (83.3%) samples belonged to different patients. Of these 190 patients, HDV RNA
      was observed in 53 (28%) patients. Of the 53 HDV positive cases, 37 (69.8%) were
      males and 16 (30.2%) were female patients. The percentage of dual infection was
      found higher significantly (p < 0.05) in male patients as compared to female
      patients. Total 41 (26.8%) patients were below 40 years and 13 (31.7%) were above
      40 years of age. No significant difference was seen in patients with ages above
      or below 40 years. In the provinces of Sindh, Khyber Pakhtoonkhaw and Punjab the
      observed prevalence of HDV was 67%, 6% and 4% respectively.In conclusion, the HDV
      infection is not uncommon in Pakistan and its prevalence is higher significantly
      in the Province of Sindh (p < 0.01) and male six (p < 0.05).

PMID- 21888672
TI  - Refining transcriptional programs in kidney development by integration of deep
      RNA-sequencing and array-based spatial profiling.
AB  - BACKGROUND: The developing mouse kidney is currently the best-characterized model
      of organogenesis at a transcriptional level. Detailed spatial maps have been
      generated for gene expression profiling combined with systematic in situ
      screening. These studies, however, fall short of capturing the transcriptional
      complexity arising from each locus due to the limited scope of microarray-based
      technology, which is largely based on "gene-centric" models. RESULTS: To address
      this, the polyadenylated RNA and microRNA transcriptomes of the 15.5 dpc mouse
      kidney were profiled using strand-specific RNA-sequencing (RNA-Seq) to a depth
      sufficient to complement spatial maps from pre-existing microarray datasets. The
      transcriptional complexity of RNAs arising from mouse RefSeq loci was catalogued;
      including 3568 alternatively spliced transcripts and 532 uncharacterized
      alternate 3' UTRs. Antisense expressions for 60% of RefSeq genes was also
      detected including uncharacterized non-coding transcripts overlapping kidney
      progenitor markers, Six2 and Sall1, and were validated by section in situ
      hybridization. Analysis of genes known to be involved in kidney development,
      particularly during mesenchymal-to-epithelial transition, showed an enrichment of
      non-coding antisense transcripts extended along protein-coding RNAs. CONCLUSION:
      The resulting resource further refines the transcriptomic cartography of kidney
      organogenesis by integrating deep RNA sequencing data with locus-based
      information from previously published expression atlases. The added resolution of
      RNA-Seq has provided the basis for a transition from classical gene-centric
      models of kidney development towards more accurate and detailed "transcript
      centric" representations, which highlights the extent of transcriptional
      complexity of genes that direct complex development events.

PMID- 21888673
TI  - The association between urinary kidney injury molecule 1 and urinary cadmium in
      elderly during long-term, low-dose cadmium exposure: a pilot study.
AB  - BACKGROUND: Urinary kidney injury molecule 1 is a recently discovered early
      biomarker for renal damage that has been proven to be correlated to urinary
      cadmium in rats. However, so far the association between urinary cadmium and
      kidney injury molecule 1 in humans after long-term, low-dose cadmium exposure has
      not been studied. METHODS: We collected urine and blood samples from 153 non
      smoking men and women aged 60+, living in an area with moderate cadmium pollution
      from a non-ferrous metal plant for a significant period. Urinary cadmium and
      urinary kidney injury molecule 1 as well as other renal biomarkers (alpha1
      microglobulin, beta2-microglobulin, blood urea nitrogen, urinary proteins and
      microalbumin) were assessed. RESULTS: Both before (r = 0.20; p = 0.01) and after
      (partial r = 0.32; p < 0.0001) adjustment for creatinine, age, sex, past smoking,
      socio-economic status and body mass index, urinary kidney injury molecule 1
      correlated with urinary cadmium concentrations. No significant association was
      found between the other studied renal biomarkers and urinary cadmium.
      CONCLUSIONS: We showed that urinary kidney injury molecule 1 levels are
      positively correlated with urinary cadmium concentration in an elderly population
      after long-term, low-dose exposure to cadmium, while other classical markers do
      not show an association. Therefore, urinary kidney injury molecule 1 might be
      considered as a biomarker for early-stage metal-induced kidney injury by cadmium.

PMID- 21888674
TI  - Long-term exposure to traffic-related air pollution and type 2 diabetes
      prevalence in a cross-sectional screening-study in the Netherlands.
AB  - BACKGROUND: Air pollution may promote type 2 diabetes by increasing adipose
      inflammation and insulin resistance. This study examined the relation between
      long-term exposure to traffic-related air pollution and type 2 diabetes
      prevalence among 50- to 75-year-old subjects living in Westfriesland, the
      Netherlands. METHODS: Participants were recruited in a cross-sectional diabetes
      screening-study conducted between 1998 and 2000. Exposure to traffic-related air
      pollution was characterized at the participants' home-address. Indicators of
      exposure were land use regression modeled nitrogen dioxide (NO2) concentration,
      distance to the nearest main road, traffic flow at the nearest main road and
      traffic in a 250 m circular buffer. Crude and age-, gender- and neighborhood
      income adjusted associations were examined by logistic regression. RESULTS: 8,018
      participants were included, of whom 619 (8%) subjects had type 2 diabetes.
      Smoothed plots of exposure versus type 2 diabetes supported some association with
      traffic in a 250 m buffer (the highest three quartiles compared to the lowest
      also showed increased prevalence, though non-significant and not increasing with
      increasing quartile), but not with the other exposure metrics. Modeled NO2
      concentration, distance to the nearest main road and traffic flow at the nearest
      main road were not associated with diabetes. Exposure-response relations seemed
      somewhat more pronounced for women than for men (non-significant). CONCLUSIONS:
      We did not find consistent associations between type 2 diabetes prevalence and
      exposure to traffic-related air pollution, though there were some indications for
      a relation with traffic in a 250 m buffer.

PMID- 21888675
TI  - "Food company sponsors are kind, generous and cool": (mis)conceptions of junior
      sports players.
AB  - BACKGROUND: Children's exposure to unhealthy food marketing influences their food
      knowledge, preferences and consumption. Sport sponsorship by food companies is
      widespread and industry investment in this marketing is increasing. This study
      aimed to assess children's awareness of sport sponsors and their brand-related
      attitudes and purchasing intentions in response to this marketing. METHODS:
      Sports clubs known to have food sponsors and representing the most popular sports
      for Australian children across a range of demographic areas were recruited.
      Interview-based questionnaires were conducted at clubs with children aged 10-14
      years (n = 103) to examine their recall of local sports club and elite sport
      sponsors, and their attitudes towards sponsors and sponsorship activities.
      RESULTS: Most children (68%) could recall sponsors of their sports club, naming a
      median of two sponsors, including a median of one food company sponsor each.
      Almost half (47%) of children could recall any sponsors of their favourite elite
      sporting team. Children aged 10-11 years were more likely than older children to
      report that they thought about sponsors when buying something to eat or drink (P
      < 0.01); that they liked to return the favour to sponsors by buying their
      products (P < 0.01); and that sponsors were 'cool' (P = 0.02). Most children had
      received a voucher or certificate from a food or beverage company to reward sport
      performance (86% and 76%, respectively). Around one-third of children reported
      liking the company more after receiving these rewards. CONCLUSIONS: Children's
      high recall of food and beverage company sport sponsors and their positive
      attitudes towards these sponsors and their promotions is concerning as this is
      likely to be linked to children's food preferences and consumption. Limiting
      children's exposure to this marketing is an important initiative to improve
      children's nutrition.

PMID- 21888676
TI  - DNA double-strand break induction in Ku80-deficient CHO cells following boron
      neutron capture reaction.
AB  - BACKGROUND: Boron neutron capture reaction (BNCR) is based on irradiation of
      tumors after accumulation of boron compound. 10B captures neutrons and produces
      an alpha (4He) particle and a recoiled lithium nucleus (7Li). These particles
      have the characteristics of high linear energy transfer (LET) radiation and have
      marked biological effects. The purpose of this study is to verify that BNCR will
      increase cell killing and slow disappearance of repair protein-related foci to a
      greater extent in DNA repair-deficient cells than in wild-type cells. METHODS:
      Chinese hamster ovary (CHO-K1) cells and a DNA double-strand break (DSB) repair
      deficient mutant derivative, xrs-5 (Ku80 deficient CHO mutant cells), were
      irradiated by thermal neutrons. The quantity of DNA-DSBs following BNCR was
      evaluated by measuring the phosphorylation of histone protein H2AX (gamma-H2AX)
      and 53BP1 foci using immunofluorescence intensity. RESULTS: Two hours after
      neutron irradiation, the number of gamma-H2AX and 53BP1 foci in the CHO-K1 cells
      was decreased to 36.5-42.8% of the levels seen 30 min after irradiation. In
      contrast, two hours after irradiation, foci levels in the xrs-5 cells were 58.4
      69.5% of those observed 30 min after irradiation. The number of gamma-H2AX foci
      in xrs-5 cells at 60-120 min after BNCT correlated with the cell killing effect
      of BNCR. However, in CHO-K1 cells, the RBE (relative biological effectiveness)
      estimated by the number of foci following BNCR was increased depending on the
      repair time and was not always correlated with the RBE of cytotoxicity.
      CONCLUSION: Mutant xrs-5 cells show extreme sensitivity to ionizing radiation,
      because xrs-5 cells lack functional Ku-protein. Our results suggest that the DNA
      DSBs induced by BNCR were not well repaired in the Ku80 deficient cells. The RBE
      following BNCR of radio-sensitive mutant cells was not increased but was lower
      than that of radio-resistant cells. These results suggest that gamma-ray
      resistant cells have an advantage over gamma-ray sensitive cells in BNCR.

PMID- 21888677
TI  - Esmolol modulates inhibitory neurotransmission in the substantia gelatinosa of
      the spinal trigeminal nucleus of the rat.
AB  - BACKGROUND: beta1-adrenaline receptor antagonists are often used to avoid
      circulatory complications during anesthesia in patients with cardiovascular
      diseases. Of these drugs, esmolol, a short-acting beta antagonist, is also
      reported to exert antinociceptive and anesthetic sparing effects. This study was
      designed to identify the central mechanism underlying the antinociceptive effect
      of esmolol. METHODS: Wistar rats (7-21 d, 17-50 g) were anesthetized with
      ketamine (100-150 mg/kg) or isoflurane (5%) and decapitated. Horizontal slices
      (400-MUm thick) of the lower brainstem containing the substantia gelatinosa (SG)
      of the caudal part of the spinal trigeminal nucleus (Sp5c), in which the
      nociceptive primary afferents form the first intracranial synapses, were made
      with a vibrating slicer. The miniature inhibitory and excitatory postsynaptic
      currents (mIPSCs and mEPSCs, respectively) were simultaneously recorded from
      visually identified SG neurons of the Sp5c in the presence of tetrodotoxin (1
      MUM). Additionally, mIPSCs were recorded during pharmacological isolation of GABA
      and glycine-mediated mIPSCs with kynurenic acid (1 mM). RESULTS: Esmolol (500
      MUM) significantly and selectively increased the mIPSC frequency (to 214.2% +/-
      34.2% of the control, mean +/- SEM, n = 35; P < 0.001), but not that of mEPSCs,
      without changing their amplitude. The increase in mIPSC frequency with esmolol
      was not affected by prior activation of beta receptors with isoproterenol (100
      MUM) but it was significantly attenuated by removal of extracellular Ca2+.
      CONCLUSIONS: These data suggest that esmolol modulates inhibitory transmitter
      release in the Sp5c through a mechanism involving Ca2+-entry but in a beta1
      adrenoceptor-independent manner. The present results suggest that the
      facilitation of inhibitory transmitter release in the central nociceptive network
      underlies, at least in part, the antinociceptive effect of esmolol.

PMID- 21888678
TI  - A randomised trial and economic evaluation of the effect of response mode on
      response rate, response bias, and item non-response in a survey of doctors.
AB  - BACKGROUND: Surveys of doctors are an important data collection method in health
      services research. Ways to improve response rates, minimise survey response bias
      and item non-response, within a given budget, have not previously been addressed
      in the same study. The aim of this paper is to compare the effects and costs of
      three different modes of survey administration in a national survey of doctors.
      METHODS: A stratified random sample of 4.9% (2,702/54,160) of doctors undertaking
      clinical practice was drawn from a national directory of all doctors in
      Australia. Stratification was by four doctor types: general practitioners,
      specialists, specialists-in-training, and hospital non-specialists, and by six
      rural/remote categories. A three-arm parallel trial design with equal
      randomisation across arms was used. Doctors were randomly allocated to: online
      questionnaire (902); simultaneous mixed mode (a paper questionnaire and login
      details sent together) (900); or, sequential mixed mode (online followed by a
      paper questionnaire with the reminder) (900). Analysis was by intention to treat,
      as within each primary mode, doctors could choose either paper or online. Primary
      outcome measures were response rate, survey response bias, item non-response, and
      cost. RESULTS: The online mode had a response rate 12.95%, followed by the
      simultaneous mixed mode with 19.7%, and the sequential mixed mode with 20.7%.
      After adjusting for observed differences between the groups, the online mode had
      a 7 percentage point lower response rate compared to the simultaneous mixed mode,
      and a 7.7 percentage point lower response rate compared to sequential mixed mode.
      The difference in response rate between the sequential and simultaneous modes was
      not statistically significant. Both mixed modes showed evidence of response bias,
      whilst the characteristics of online respondents were similar to the population.
      However, the online mode had a higher rate of item non-response compared to both
      mixed modes. The total cost of the online survey was 38% lower than simultaneous
      mixed mode and 22% lower than sequential mixed mode. The cost of the sequential
      mixed mode was 14% lower than simultaneous mixed mode. Compared to the online
      mode, the sequential mixed mode was the most cost-effective, although exhibiting
      some evidence of response bias. CONCLUSIONS: Decisions on which survey mode to
      use depend on response rates, response bias, item non-response and costs. The
      sequential mixed mode appears to be the most cost-effective mode of survey
      administration for surveys of the population of doctors, if one is prepared to
      accept a degree of response bias. Online surveys are not yet suitable to be used
      exclusively for surveys of the doctor population.

PMID- 21888679
TI  - 'Cooling and cathing' the post-resuscitated.
AB  - Cronier and co-workers provide additional evidence that routine use of mild
      therapeutic hypothermia combined with emergent coronary angiography and
      percutaneous intervention results in excellent survival with intact neurological
      function for post-resuscitation patients with ventricular fibrillation.

PMID- 21888680
TI  - Give or take? Intravenous immunoglobulin or plasma exchange for Guillain-Barre
      syndrome.
AB  - A new randomised controlled trial suggested that plasma exchange hastened removal
      from the ventilator in mechanically ventilated children with Guillain-Barre
      syndrome compared with intravenous immunoglobulin. Two larger trials in adults
      showed the opposite result.

PMID- 21888681
TI  - Should we use early less invasive hemodynamic monitoring in unstable ICU
      patients?
AB  - In the previous issue of Critical Care, Takala and colleagues presented the
      results of a multicenter study to investigate whether the early presence of less
      invasive hemodynamic monitoring improves outcome in patients admitted with
      hemodynamic instability to the intensive care unit. The authors' results suggest
      that it makes no difference. We discuss these findings and compare them to the
      literature on early goal-directed therapy in which monitors are used early but
      with a protocol.

PMID- 21888682
TI  - Revisiting Mars and Venus: understanding gender differences in critical illness.
AB  - Understanding the nature and biological basis of gender-determined differences in
      risk of and outcome from infection might identify new therapeutic targets, allow
      more individualised treatment, and facilitate better risk prediction and
      application of healthcare resources. Gender differences in behaviours,
      comorbidities, access to healthcare and biology may result in differences in
      acquiring infection, or in response to infection once acquired. Some studies have
      reported higher male susceptibility to infection, and higher risk of death with
      sepsis, but others have found the opposite effect. The explanation for this
      disagreement is probably that different studies have included patients at
      different stages on the continuum from infectious agent exposure to death or
      recovery. Studying sufficient patient numbers to explore this entire continuum
      while accounting for heterogeneity in type of infection and comorbidity is
      difficult because of the number of patients required. However, if true gender
      effects can be identified, examination of their biological or psychosocial causes
      will be warranted.

PMID- 21888683
TI  - Clinical review: Special populations--critical illness and pregnancy.
AB  - Critical illness is an uncommon but potentially devastating complication of
      pregnancy. The majority of pregnancy-related critical care admissions occur
      postpartum. Antenatally, the pregnant patient is more likely to be admitted with
      diseases non-specific to pregnancy, such as pneumonia. Pregnancy-specific
      diseases resulting in ICU admission include obstetric hemorrhage, pre
      eclampsia/eclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet
      count) syndrome, amniotic fluid embolus syndrome, acute fatty liver of pregnancy,
      and peripartum cardiomyopathy. Alternatively, critical illness may result from
      pregnancy-induced worsening of pre-existing diseases (for example, valvular heart
      disease, myasthenia gravis, and kidney disease). Pregnancy can also predispose
      women to diseases seen in the non-pregnant population, such as acute respiratory
      distress syndrome (for example, pneumonia and aspiration), sepsis (for example,
      chorioamnionitis and pyelonephritis) or pulmonary embolism. The pregnant patient
      may also develop conditions co-incidental to pregnancy such as trauma or
      appendicitis. Hemorrhage, particularly postpartum, and hypertensive disorders of
      pregnancy remain the most frequent indications for ICU admission. This review
      focuses on pregnancy-specific causes of critical illness. Management of the
      critically ill mother poses special challenges. The physiologic changes in
      pregnancy and the presence of a second, dependent, patient may necessitate
      adjustments to therapeutic and supportive strategies. The fetus is generally
      robust despite maternal illness, and therapeutically what is good for the mother
      is generally good for the fetus. For pregnancy-induced critical illnesses,
      delivery of the fetus helps resolve the disease process. Prognosis following
      pregnancy-related critical illness is generally better than for age-matched non
      pregnant critically ill patients.

PMID- 21888684
TI  - Another nail in the hammer's coffin?
AB  - Blood pressure saggy? Cardiac output low? Oliguria? Increasing acidosis?
      Peripheries a bit cool? Poor cardiac history? No problem. Just start some
      dobutamine and watch the numbers improve. And if the patient happens to die, that
      is their fault. Or is it? Catecholamines are long-established drugs that have
      never undergone formal testing of long-term outcomes and safety. Their use
      requires re-evaluation in the light of a wide range of deleterious actions and
      retrospective studies suggesting harm.

PMID- 21888685
TI  - Cardiovascular disease in systemic sclerosis--an emerging association?
AB  - Microvascular disease is a prominent feature of systemic sclerosis (SSc) and
      leads to Raynaud's phenomenon, pulmonary arterial hypertension, and scleroderma
      renal crisis. The presence of macrovascular disease is less well established,
      and, in particular, it is not known whether the prevalence of coronary heart
      disease in SSc is increased. Furthermore, in terms of cardiac involvement in SSc,
      there remains conjecture about the relative contributions of atherosclerotic
      macrovascular disease and myocardial microvascular disease. In this review, we
      summarize the literature describing cardiovascular disease in SSc, discuss the
      pathophysiological mechanisms common to SSc and atherosclerosis, and review the
      surrogate markers of cardiovascular disease which have been examined in SSc.
      Proposed mediators of the vasculopathy of SSc which have also been implicated in
      atherosclerosis include endothelial dysfunction, a reduced number of circulating
      endothelial progenitor cells, and an increased number of microparticles. Excess
      cardiovascular risk in SSc is suggested by increased arterial stiffness and
      carotid intima thickening and reduced flow-mediated dilatation. Cohort studies of
      adequate size are required to resolve whether this translates into an increased
      incidence of cardiovascular events in patients with SSc.

PMID- 21888686
TI  - Desperately looking for the right target in osteoarthritis: the anti-IL-1
      strategy.
AB  - Blocking IL-1 in patients with knee osteoarthritis is an attractive strategy.
      Cohen and colleagues report a randomised, placebo-controlled, multiple-dose trial
      using a monoclonal antibody blocking IL-1 type 1 receptor. They failed to show
      any positive results in terms of evolution of pain for up to 12 weeks, in line
      with the former trials using intraarticular injections of IL-1 receptor
      antagonist. A trend was observed, however, in a subgroup of patients with high
      level of pain at baseline. Although these data may suggest cessation of IL-1
      therapy in osteoarthritis, other methods such as limited intraarticular anti-IL-1
      delivery should still be considered.

PMID- 21888687
TI  - T-helper cells as new players in ANCA-associated vasculitides.
AB  - In anti-neutrophil cytoplasmic autoantibody-associated vasculitides (AAV),
      several observations support a key role of T-helper cells (CD4(+) T cells) in
      disease pathophysiology. An expanded population of effector memory CD4(+) T cells
      in AAV patients may contribute to tissue injury and disease progression. In
      addition, functional impairment of regulatory T cells (T(Regs)) is reported in
      AAV patients. A fraction of T(Regs) have the capacity to differentiate into Th17
      cells in the context of a proinflammatory environment. Therefore,
      nonfunctionality of T(Regs) described in AAV patients may be caused by their
      conversion into IL-17-producing cells that may contribute to granulomatous
      vasculitis. Further investigations directed at the plasticity of T(Regs) in AAV
      patients are warranted.

PMID- 21888689
TI  - Challenges in understanding Sjogren's syndrome--improved insights into the
      pathogenesis generate hope for innovative therapies?
AB  - The reviews in this series on Sjogren syndrome provide an up-to-date summary and
      perspectives on the pathogenesis of this interesting entity with glandular and
      frequently systemic manifestations, the value of preclinical models, and our
      current understanding of therapeutic approaches. The last of these includes what
      has been learned from trials blocking tumor necrosis factor and, more recently,
      anti-CD20 therapy. Potential therapeutic targets, such as blockade of the B cell
      activating factor, the role of interferon-alpha, and targeting CD22, are
      discussed.

PMID- 21888688
TI  - Immunopathologic differences of Sjogren's syndrome versus sicca syndrome in HCV
      and HIV infection.
AB  - A clinical picture of dry eye and dry mouth with the histological counterpart of
      focal lymphocytic sialoadenitis, usually detected in minor salivary glands, is
      considered the hallmark of Sjogren's syndrome. The association of sicca
      complaints and focal sialoadenitis can be also found in a number of other
      diseases, including some systemic viral infections. Among these conditions,
      chronic hepatitis C virus infection, associated with mixed cryoglobulinaemia and
      extra-hepatic manifestations, and HIV infection, particularly in the phase of
      diffuse interstitial lymphocytic infiltration, may mimic the clinical and
      histological aspects of Sjogren's syndrome. However, each disorder is
      characterised by specific, disease-related immunopathological aspects. Besides
      sicca complaints, the various disorders may also share a number of systemic extra
      glandular features and the possible development of mucosa-associated lymphoid
      tissue lymphomas. This latter event represents in all of these diseases the final
      result of an antigen-driven chronic stimulation of B lymphocytes.

PMID- 21888690
TI  - Clinical review: Thinking outside the box--an iconoclastic view of current
      practice.
AB  - Many advances in medicine have been achieved through challenging established
      dogma with revolutionary thought and novel practices. Each and every specialty is
      reinvigorated by regular re-evaluation of processes and practices in the light of
      new evidence and fresh conceptualization. Challenge can galvanize fresh thinking
      and new approaches, yet may also reinforce and strengthen traditional paradigms
      if the prevailing orthodoxy is subsequently revalidated. This article is a
      synopsis of a roundtable meeting held in Brussels in March 2010 designed
      specifically to confront doctrine with reasoned scientific argument, and to
      propose new ideas for advancing critical care practices and outcomes.

PMID- 21888691
TI  - MicroRNAs miR-221 and miR-222: a new level of regulation in aggressive breast
      cancer.
AB  - MicroRNAs (miRNAs) are crucial in the initiation and progression of tumors. A
      recent study has reported that the miRNAs miR-221 and miR-222 are involved in the
      promotion of an aggressive basal-like phenotype in breast cancer, functioning
      downstream of the RAS pathway and triggering epithelial-to-mesenchymal
      transition. These new insights into the roles of miR-221/222 in breast cancer
      metastasis, drug resistance and RAS pathways could potentially have applications
      in medical practice.

PMID- 21888692
TI  - Technical aspects of amyloid imaging for Alzheimer's disease.
AB  - [11C]Pittsburgh Compound B positron emission tomography has now been extensively
      used to evaluate the amyloid load in different types of dementia and has become a
      powerful research tool in the field of neurodegenerative diseases. In the present
      short review we discuss the properties of amyloid imaging agent [11C]Pittsburgh
      Compound B, the different modalities of molecular imaging, image processing and
      data analysis, and newer amyloid imaging agents.

PMID- 21888695
TI  - Cell phones and male infertility: a review of recent innovations in technology
      and consequences.
AB  - Cell phones have become a vital part of everyday life. However, the health risks
      associated with their usage are often overlooked. Recently, evidence from several
      studies supports a growing claim that cell phone usage may have a detrimental
      effect on sperm parameters leading to decreased male fertility. Nonetheless,
      other studies showed no conclusive link between male infertility and cell phone
      usage. The ambiguity of such results is attributed to the lack of a centralized
      assay for measuring inflicted damage caused by cell phones. Study design, ethics,
      and reproducibility are all aspects which must be standardized before any
      conclusions can be made.

PMID- 21888696
TI  - Initial experience of a novel ergonomic surgical chair for laparoscopic pelvic
      surgery.
AB  - INTRODUCTION: We present the initial experience of a novel surgical chair for
      laparoscopic pelvic surgery, the ETHOSTM (Bridge City Surgical, Portland, OR).
      MATERIALS AND METHODS: The ETHOS chair has an adjustable saddle height that
      ranges from 0.89 to 1.22 m high, an overall width of 0.89 m, and a depth of 0.97
      m. The open straddle is 0.53 m and fits most OR tables. We performed 7 pelvic
      laparoscopy cases with the 1st generation ETHOSTM platform including 2
      laparoscopic ureteral reimplantations, 5 laparoscopic pelvic lymphadenectomies
      for staging prostate cancer in which one case involved a laparoscopic radical
      retropubic prostatectomy, performed by 2 different surgeons. RESULTS: All 7
      pelvic laparoscopic procedures were successful with the ETHOSTM chair. No
      conversion to open surgery was necessary. Survey done by surgeons after the
      procedures revealed minimal stress on back or upper extremities by the surgeons
      from these operations even when surgery was longer than 120 minutes. Conversely,
      the surgical assistants still had issues with their positions since they were on
      either sides of the patient stressing their positions during the procedure.
      CONCLUSION: The ETHOS chair system allows the surgeon to operate seated in
      comfortable position with ergonomic chest, arms, and back supports. These
      supports minimize surgeon fatigue and discomfort during pelvic laparoscopic
      procedures even when these procedures are longer than 120 minutes without
      consequence to the patient safety or detrimental effects to the surgical team.

PMID- 21888697
TI  - Robotic-assisted partial Nephrectomy: initial experience in South America.
AB  - OBJECTIVE: To report the initial outcomes of robotic-assisted partial nephrectomy
      in a tertiary center in South America. MATERIAL AND METHODS: From 11/2008 to
      12/2009, a total of 16 transperitoneal robotic-assisted partial nephrectomies
      were performed in 15 patients to treat 18 kidney tumors. One patient with
      bilateral tumor had two procedures, while two patients with two synchronous
      unilateral tumors had a single operation to remove them. Eleven (73%) patients
      were male and the right kidney was affected in 7 (46%) patients. The median
      patient age and tumor size were 57 years old and 30 mm, respectively. Five (28%)
      tumors were hilar and/or centrally located. RESULTS: The median operative time,
      warm ischemia time and estimated blood loss was 140 min, 27 min and 120 mL,
      respectively. Blood transfusion was required in one patient with bilateral tumor,
      and one additional pyelolithotomy was performed due to a 15 mm stone located in
      the renal pelvis. The histopathology analysis showed 15 (83%) malignant tumors,
      which 10 (67%) were clear cell carcinoma. The median hospital stay was 72 hrs and
      no major complication was observed. CONCLUSION: Robotic-assisted partial
      nephrectomy is safe and represents a valuable option to perform minimally
      invasive nephron-sparing surgery.

PMID- 21888698
TI  - The efficacy and safety of oral Tamsulosin controlled absorption system (OCAS)
      for the treatment of lower urinary tract symptoms due to bladder outlet
      obstruction associated with benign prostatic hyperplasia: an open-label
      preliminary study.
AB  - AIMS: Tamsulosin, a superselective subtype alpha 1a and 1d blocker, is used for
      the treatment of male lower urinary tract symptoms (LUTS) commonly caused by
      benign prostatic hyperplasia (BPH). This prospective study evaluated the efficacy
      and safety of a new formulation, Tamsulosin OCAS(r) (Oral Controlled Absorption
      System), for LUTS associated with BPH in Thai patients. MATERIALS AND METHODS:
      Fifty one patients over 40 years old with complaints of LUTS associated with BPH
      were recruited. Patients received an 8 week course of once daily 0.4 mg
      tamsulosin OCAS(r), and were followed up at 2 (visit 3), 4 (visit 4) and 8 (visit
      5) weeks post-treatment. At each visit, patients were assessed using the
      International Prostate Symptom Score (IPSS), Nocturia Quality of Life (N-QoL)
      Questionnaire, QoL Assessment Index (IPSS-QoL), and International Index of
      Erectile Function (IIEF). The primary outcome was efficacy of Tamsulosin. The
      secondary outcomes included change in the mean number of nocturia episodes, hours
      of undisturbed sleep (HUS) and uroflowmetry measurements. RESULTS: Total IPSS
      significantly decreased at week 8 from baseline (from 19.52 to 6.08; p < 0.001).
      Similarly, the voiding and storage subscores of IPSS also continued to improve
      significantly starting from the second and third visits, respectively (p < 0.001
      versus baseline). The IPSS-QoL and N-QoL scores significantly improved at visit 3
      through end of study. In addition, we observed significant nocturia and HUS
      improvement in their last clinic visit. Uroflowmetry parameters, Qmax and Qave,
      improved significantly at 3rd clinic visit. Three patients experienced mild
      dizziness. CONCLUSION: Tamsulosin OCAS(r) treatment led to significant
      improvements in LUTS, HUS and QoL in Thai patients with bladder outlet
      obstruction from BPH with few side effects.

PMID- 21888699
TI  - Steinstrasse predictive factors and outcomes after extracorporeal shockwave
      lithotripsy.
AB  - PURPOSE: Urinary stone disease is a common medical problem. Extracorporeal
      shockwave lithotripsy (SWL) has been applied with high success and low
      complication rates. Steinstrasse (SS) is a possible complication after SWL. The
      aim of the present study was to prospectively evaluate the factors and outcomes
      associated with SS after SWL. MATERIALS AND METHODS: We have prospectively
      evaluated 265 SWL sessions (2005-2009). Two lithotriptors were used randomly:
      Siemens Lithostar and Dornier Compact S. All patients had imaging exams after 30
      and 90 days or according to symptoms. RESULTS: SS was observed in 14 (5.3%) out
      of 265 SWL procedures (n = 175 patients, 51.5% women/48.5% men, mean +/- SD age =
      46.3 +/- 15.5 years). SS was more common after SWL for pelviureteral calculi
      rather than caliceal stones (p = 0.036). There was a trend toward more
      occurrences of SS after SWL for larger stone area (> 200 mm2, p = 0.072).
      Preoperative ureteral stent didn't prevent SS. SWL machine, intensity, number of
      pulses and frequency were not associated with SS formation. Post-SWL pain, fever
      and gravel elimination were factors associated with SS (p = 0.021; p = 0.011; p =
      0.078). When SS occurred, treatment modalities included Medical Expulsive Therapy
      (MET), ureteroscopy and SWL. CONCLUSIONS: Steinstrasse is an uncommon event after
      SWL and seems to occur more frequently with larger pelviureteral stones.
      Impaction of stones is more frequent in the middle ureter. All patients should be
      followed after SWL, but SS should be specially suspected if there is macroscopic
      gravel elimination, flank pain and/or fever. When SS occurs, treatment should be
      promptly introduced, including medical expulsive therapy, surgical approach or
      SWL in selected cases. Further prospective studies are awaited to evaluated
      preventive measures for SS occurrence.

PMID- 21888700
TI  - Periurethral constrictor: late results of the treatment of post prostatectomy
      urinary incontinence.
AB  - OBJECTIVES: We evaluated retrospectively, the long-term outcome of patients with
      post-prostatectomy urinary incontinence (PPUI) after placement of the
      Periurethral Constrictor (PUC). MATERIALS AND METHODS: Fifty-six men with severe
      PPUI were studied, with a mean age of 68.5 years old. Fifty-one men had PPUI due
      to radical surgery having the device placed around the bulbous urethra, and five
      individuals with benign prostatic hypertrophy (BPH) had placement around the
      bladder neck. The mean follow-up was 82.2 months. RESULTS: Twenty-two patients
      (39.28%) became continent (0 to 1 pad a day) and 34 (60.72%) were incontinent.
      Complications were as follows: urethral erosion in 15 (26.78%); mechanical
      malfunction in 2 (3.5%); infection in 2 (3.5%); urinary fistula in 1 (1.7%);
      Urinary tract infection1 (1.7%). Twenty-three patients needed to have the device
      removed (41.07%). Success rate (continent me) was 30.35%. CONCLUSION: In the
      present series the PUC was not effective for the treatment of severe PPUI in the
      long-term follow-up.

PMID- 21888701
TI  - Single institution experience with the transobturator sling suspension system
      AdVance(r) in the treatment of male urinary incontinence: mid-term results.
AB  - PURPOSE: To evaluate the clinical outcome after placement of AdVance(r) sling in
      men with stress urinary incontinence after prostate surgery. MATERIALS AND
      METHODS: Incontinence was assessed on basis of number of pad usage. Patients'
      satisfaction was evaluated using a non-validated patient questionnaire at 12
      months post-operatively. RESULTS: Incontinence cure rate (no pad usage) was 61.5%
      (16/26) and improvement (1-2 pads per day) was seen in 26.9% (7/26). No
      improvement was observed in 11.5% (3/26) of patients. A total of 87.5% (21/24) of
      patients were very satisfied with the operation 22 months after surgery. Success
      rate in patients with prior radiation therapy (20% cure; 40% improvement) was
      significantly worse. CONCLUSIONS: Placement of the AdVance(r) sling represents an
      effective and safe treatment option for patients with post prostate surgery
      incontinence. Patients that underwent radiotherapy after prostate surgery had
      lower success rate.

PMID- 21888702
TI  - Apoptotic markers in semen of infertile men: Association with cigarette smoking.
AB  - OBJECTIVES: (i) To examine the role of apoptosis in the pathogenesis of DNA
      damage in semen from infertile men. (ii) To assess the effects of smoking on
      apoptotic markers and seminal parameters among infertile men. (iii) To assess the
      correlation of apoptosis with conventional semen parameters. MATERIALS AND
      METHODS: The study was carried out on 70 men with idiopathic infertility, divided
      into two groups: thirty infertile non smokers and forty infertile smokers. In
      addition to 60 fertile men (30 non smokers and 30 smokers) as control group. Each
      subject provided semen for analysis of parameters, determination of % of DNA
      fragmentation, s-Fas, caspase-3 activity levels and cotinine levels. RESULTS: The
      results revealed that infertile men, particularly smokers have significantly
      lower semen variables and significantly higher levels of apoptotic variables (%
      of DNA fragmentation, s-Fas and caspase-3 activity) in addition to cotinine.
      CONCLUSIONS: The present findings provide additional evidence supporting the
      importance of the evaluation of apoptotic markers to test male infertility
      particularly among smokers.

PMID- 21888703
TI  - Socioeconomic status is an independent predictor of biochemical recurrence among
      patients with prostate cancer who undergo radical prostatectomy.
AB  - PURPOSE: Socioeconomic status (SES) may influence cancer characteristics and
      behavior in several aspects. We analyzed PCa characteristics and behavior among
      low income uninsured men, and compare them to high income patients with health
      insurance in a developing country. MATERIALS AND METHODS: A retrospective case
      control study was performed on 934 patients with clinically localized PCa who
      underwent radical prostatectomy between March, 1999 and July, 2009. Patients were
      divided in two groups, according to their SES. In group 1 (n =380), all had low
      income, low educational levels and couldn ' t afford medical insurance. In group
      2 (n =554), all had higher income, higher education and had medical insurance.
      RESULTS: Patients from group 1 were older, had higher Gleason scores, higher
      rates of seminal vesicle and bladder neck involvement. The Kaplan Meier disease
      free survival curve demonstrated that after a follow-up of four years, about 50%
      of uninsured patients had biochemical recurrence, versus 21% of insured patients
      (Log rank test: p < 0.001). A multivariate Cox regression analysis for the risk
      of disease recurrence demonstrated that only PSA levels, Gleason score, seminal
      vesicle involvement and SES were statistically significant variables. Patients
      with a low SES presented 1.8 times the risk of recurrence as compared to patients
      with a high SES. CONCLUSIONS: Patients with low SES were older, presented more
      aggressive PCa characteristics and a high rate of disease recurrence. A low SES
      constituted an independent predictor for disease recurrence.

PMID- 21888704
TI  - Renal tumor and trauma: a pitfall for conservative (correction of conversative)
      management.
AB  - PURPOSE: Conservative management has been largely used for renal trauma. Although
      this approach is safe and highly recommended, it can hide a pre-existing unknown
      condition, such as tumors or urinary malformations. A high index of suspicion is
      needed for early recognition of these conditions. We present four cases treated
      at the Pediatric Oncology Institute - Federal University of Sao Paulo, which have
      been initially treated conservatively for renal trauma. MATERIALS AND METHODS: We
      reviewed all 218 renal cases of renal tumors treated at our institution in a 22
      year period, searching for associated trauma events. RESULTS: Four cases of renal
      tumors were initially treated conservatively for blunt renal trauma of low energy
      mechanism. Patients ' ages ranged from 7 to 12 years old. Two patients had no
      previous symptoms, one patient had hematuria and another had an abdominal mass.
      Computerized Axial Tomography (CT) of the abdomen revealed disparate magnitude of
      the renal bleeding to the low energy mechanism of trauma. All patients underwent
      surgical treatment. Kidney specimens showed Wilms tumor in three cases and renal
      carcinoma in one. CONCLUSIONS: The association between renal tumors and trauma
      should be suspected when renal trauma hemorrhage on abdominal CT scan does not
      match the low energy mechanism of blunt abdominal trauma. The key for a
      successful diagnosis of renal tumor or congenital malformations is the high index
      of suspicion for these conditions.

PMID- 21888705
TI  - Comparison of the outcomes of the sling technique using a commercial and hand
      made polypropylene sling.
AB  - PURPOSE: To compare the outcomes and costs of stress urinary incontinence (SUI)
      surgery using a hand-made sling (Marlex(r)) versus a commerciallyavailable
      suburethral polypropylene sling (Advantage(r)). MATERIALS AND METHODS: Thirty
      nine women with SUI due to bladder neck hypermobility and/or sphincter
      incompetence diagnosed by clinical examination and urodynamic studies were
      divided into two groups: group 1 (n = 19) consisted of patients from an academic
      center (Department of Urology, University Hospital of Federal University of
      Maranhao, and group 2 (n = 20) patients from private practice. The hand-made
      polypropylene suburethral sling was used in group 1 and the commercial sling in
      group 2. The patients were evaluated 30, 60 and 90 days after surgery. RESULTS:
      The mean duration of surgery was 43 min. in group 1 and 51 min. in group 2. No
      postoperative voiding difficulties were observed in group 1 (100%), as well as,
      in 94.7% of patients of group 2. A bladder catheter was not required in any of
      the patients of the two groups at the end of the study. The level of satisfaction
      was 100% in group 1, whereas, one patient of group 2 considered the surgery to be
      unsuccessful. Urodynamic studies showed low amplitude uninhibited contraction in
      11.1% of patients of group 1 and 10.5% of group 2. No complications were observed
      in either group. CONCLUSION: The hand-made polypropylene mesh (Marlex(r)) can be
      used for sling procedures, saving costs and yielding results similar to that
      obtained with commercial sling systems.

PMID- 21888706
TI  - Obesity and smoking: are they modulators of cough intravesical peak pressure in
      stress urinary incontinence?
AB  - PURPOSE: SUI (Stress Urinary Incontinence) results from sudden increases in
      intravesical peak pressures exceeding urethral resistance leading to involuntary
      urine loss. Obesity and smoking are well established reversible risk factors for
      SUI and may alter intravesical peak pressures. BMI, smoking status, and other
      clinical factors were studied to determine their relationship to CIPP (maximal
      Intravesical Peak Pressures generated by Cough) in SUI complaining women.
      MATERIALS AND METHODS: Three hundred nineteen women complaining of SUI were
      evaluated with medical history and urodynamics. Age, parity, comorbidities,
      previous surgery, BMI and history of smoking were obtained. The maximal
      intravesical peak pressures generated by cough (CIPP) and cough leak point
      pressure (CLPP) were acquired. Univariate and multivariate analysis were
      conducted. RESULTS: Current smokers and former smokers had similar CIPP (170cmH2O
      and 170cmH2O; p = 0.5, respectively); Those individuals who had never smoked had
      significantly lower CIPP (140cmH2O; p = 0.000 and p = 0.009 respectively). BMI
      was directly related to CIPP (r = 0.41; p = 0.000). Vaginal deliveries (r = 
      0.15, p = 0.08) and diabetes (r = 0.15, p = 0.016) were also directly related to
      CIPP on univariate analysis. Only smoking status (p = 0.000) and BMI (p = 0.000)
      were independently significantly related to CIPP on multivariate analysis.
      CONCLUSIONS: Obesity and smoking showed increased CIPP (maximal Intravesical Peak
      Pressures generated by Cough). While reduced BMI is related to lower CIPP,
      smoking cessation does not appear to diminish CIPP. These findings suggest that
      weight loss may reduce incontinence by CIPP modulation. However, the benefits of
      smoking cessation without additional lifestyle modification, may have no benefit
      to improve urinary incontinence.

PMID- 21888707
TI  - Testicular epidermoid cyst - Ultrasound and MR typical findings with macroscopy
      correlation.

PMID- 21888726
TI  - Account-ability.

PMID- 21888727
TI  - Surveying the ashes: experience from the 2007 Peloponnese wildfires six months
      after the disaster.
AB  - INTRODUCTION: Major disasters disrupt the infrastructure of communities and have
      lasting psychological, economic, and environmental effects on the affected areas.
      The psychological status and community effects of the devastating 2007 wildfires
      on the Peloponnese Peninsula of Greece were assessed six months following the
      disaster. METHODS: Adult inhabitants, 18-65 years of age, living in villages
      affected by the wildfires were selected randomly and compared with a
      demographically similar group living in neighboring villages that were unaffected
      by the fires. Regions were chosen based on the extent of fire damage in that
      area. There were 409 participants in the fire group, and 391 in the control
      group. Participants completed a questionnaire that included the SCL-90-R symptom
      checklist, a subjective perception of health status, and a series of items
      assessing views about current problems, personal values, and trust in different
      institutions. RESULTS: The fire group scored significantly higher on
      psychological distress compared to the control group. Both groups viewed their
      health status in the previous year as better than at the present time. There were
      few significant differences between groups in the designation of regional
      problems, attitudes, and values. In the total sample, 41.6% listed unemployment,
      and 15.0% listed poverty as the most important problem in their region. The
      Church was indicated as the most trusted institution by 36.7% of the group and
      the Government by 13.3%. A total of 30.2% did not have a trusted institution.
      CONCLUSIONS: The hardiness and resilience of the fire-impacted group was evident.
      However, an improvement in economic conditions is needed to maintain the health
      and enhance the quality of life of the population living in the Peloponnese
      region. This improvement likely would have a positive effect on the attitude of
      trust in government institutions.

PMID- 21888728
TI  - Evaluation of a standardized morbidity surveillance form for use during disasters
      caused by natural hazards.
AB  - INTRODUCTION: Surveillance for health outcomes is critical for rapid responses
      and timely prevention of disaster-related illnesses and injuries after a disaster
      causing event. The Disaster Surveillance Workgroup (DSWG) of the US Centers for
      Disease Control and Prevention developed a standardized, single-page, morbidity
      surveillance form, called the Natural Disaster Morbidity Surveillance Individual
      Form (Morbidity Surveillance Form), to describe the distribution of injuries and
      illnesses, detect outbreaks, and guide timely interventions during a disaster.
      PROBLEM: Traditional data sources can be used during a disaster; however,
      supplemental active surveillance may be required because traditional systems
      often are disrupted, and many persons will seek care outside of typical acute
      care settings. Generally, these alternative settings lack health surveillance and
      reporting protocols. The need for standardized data collection was demonstrated
      during Hurricane Katrina, as the multiple surveillance instruments that were
      developed and deployed led to varied and uncoordinated data collection methods,
      analyses, and morbidity data reporting. Active, post-event surveillance of
      affected populations is critical for rapid responses to minimize and prevent
      morbidity and mortality, allocate resources, and target public health messaging.
      METHODS: The CDC and the Georgia Department of Public Health (GDPH) conducted a
      study to evaluate a Morbidity Surveillance Form to determine its ability to
      capture clinical presentations. The form was completed for each patient evaluated
      in an emergency department (ED) during triage from 01 August, 2007 through 07
      August, 2007. Data from the form were compared with the ED discharge diagnoses
      from electronic medical records, and kappa statistics were calculated to assess
      agreement. RESULTS: Nine hundred forty-nine patients were evaluated, 41% were
      male and 57% were Caucasian. According to the forms, the most common reasons for
      seeking treatment were acute illness, other (29%); pain (12%); and
      gastrointestinal illness (8%). The frequency of agreement between discharge
      diagnoses and the form ranged from 3 to 100%. Kappa values ranged from 0.23-1.0,
      with nine of the 12 categories having very good or good agreement. CONCLUSION:
      With modifications to increase sensitivity for capturing certain clinical
      presentations, the Morbidity Surveillance Form can be a useful tool for capturing
      data needed to guide public health interventions during a disaster. A validated
      collection instrument for a post-disaster event facilitates rapid and
      standardized comparison and aggregation of data across multiple jurisdictions,
      thus, improving the coordination, timeliness, and accuracy of public health
      responses. The DSWG revised the Morbidity Surveillance Form based on information
      from this study.

PMID- 21888729
TI  - Impact of the 26 December 2003 Bam Earthquake on activities of daily living and
      instrumental activities of daily living of older people.
AB  - INTRODUCTION: This study compares self-reported Activities of Daily Living (ADL)
      and Instrumental Activities of Daily Living (IADL) status among elderly survivors
      of the 2003 Bam Earthquake before, two months after, and five years after the
      event, and explores related determinants. METHODS: A two-stage cluster survey was
      conducted on 210 elderly survivors in the earthquake-stricken area five years
      after the event. RESULTS: Both ADL and IADL scores decreased two months after
      earthquake compared to prior status (p <0.001). No differences were observed
      between two months and five years after the event (p >0.05). Access to medical
      services were not related to level of ADL or IADL (p = 0.52 and p = 0.74,
      respectively). Elderly survivors with lower functional capability in terms of ADL
      experienced more problems in access to relief items (p = 0.04), but no similar
      association was found for IADL (p = 0.26). CONCLUSION: The Bam earthquake
      adversely affected functional capacity of the elderly. Disaster responders must
      take into account functional capacity of elders when planning for medical and
      relief operations.

PMID- 21888730
TI  - Research issues for nursing and midwifery contributions in emergencies.
AB  - This special report was prepared as a white paper for the First World Health
      Organization (WHO) Consultation on Nursing and Midwifery Contributions in
      Emergencies held in Geneva on 22-24 November 2006. Pertinent issues related to
      research of nurses and midwives were identified based on prior international
      conferences. Using this information, gaps between the current and proposed state
      of preparedness research activities were identified. Global perspective
      recommendations were made for consideration by the WHO and other nursing
      organizations. Finally, possible discussion questions were posed that were used
      during the consultation, but could also be used in other international nursing
      conferences.

PMID- 21888731
TI  - Infectious respiratory disease outbreaks and pregnancy: occupational health and
      safety concerns of Canadian nurses.
AB  - INTRODUCTION: This paper is a report of a qualitative study of emergency and
      critical care nurses' perceptions of occupational response and preparedness
      during infectious respiratory disease outbreaks including severe acute
      respiratory syndrome (SARS) and influenza. PROBLEM: Healthcare workers,
      predominantly female, face occupational and personal challenges in their roles as
      first responders/first receivers. Exposure to SARS or other respiratory pathogens
      during pregnancy represents additional occupational risk for healthcare workers.
      METHODS: Perceptions of occupational reproductive risk during response to
      infectious respiratory disease outbreaks were assessed qualitatively by five
      focus groups comprised of 100 Canadian nurses conducted between 2005 and 2006.
      RESULTS: Occupational health and safety issues anticipated by Canadian nurses for
      future infectious respiratory disease outbreaks were grouped into four major
      themes: (1) apprehension about occupational risks to pregnant nurses; (2) unknown
      pregnancy risks of anti-infective therapy/prophylaxis; (3) occupational risk
      communication for pregnant nurses; and (4) human resource strategies required for
      pregnant nurses during outbreaks. The reproductive risk perceptions voiced by
      Canadian nurses generally were consistent with reported case reports of pregnant
      women infected with SARS or emerging influenza strains. Nurses' fears of
      fertility risks posed by exposure to infectious agents or anti-infective therapy
      and prophylaxis are not well supported by the literature, with the former not
      biologically plausible and the latter lacking sufficient data. CONCLUSIONS:
      Reproductive risk assessments should be performed for each infectious respiratory
      disease outbreak to provide female healthcare workers and in particular pregnant
      women with guidelines regarding infection control and use of anti-infective
      therapy and prophylaxis.

PMID- 21888732
TI  - Trial to end ambulance diversion in Boston: report from the conference of the
      Boston teaching hospitals consortium.
AB  - INTRODUCTION: Annual ambulance diversion hours in Boston increased more than six
      fold from 1997 to 2006. Although interventions and best practices were
      implemented, there was no reduction in the number of diversion hours. OBJECTIVES:
      A consortium of Boston teaching hospitals instituted a two-week moratorium on
      citywide diversion from 02 October 2006 to 15 October 2006. The hypothesis was
      that there would be no significant difference in measures of hospital and
      emergency medical services (EMS) efficiency compared with the two weeks
      immediately prior. METHODS: A total of nine hospitals and the municipal emergency
      medical services in Boston submitted data for analysis. The following mean daily
      hospital measures were studied: (1) emergency department volume; (2) number of
      emergency department admissions; (3) length of stay (LOS) for all patients; and
      (4) number of elopements. Mean EMS at-hospital time by destination and the
      percent of all Boston EMS transports to each hospital destination were
      calculated. The median differences (MD) were calculated as "before" minus
      "during" the study period and were compared with paired, Wilcoxon, non-parametric
      tests. Additional mean EMS measures for all destinations included: (1) to
      hospital time; (2) number of responses with transport initiated per day; (3)
      incident entry to arrival; and (4) at-hospital time. RESULTS: The LOS for
      admitted patients (MD = 0.30 hours; IQR 0.10,1.30; p = 0.03) and number of daily
      admissions (MD = -1.50 patients; IQR -1.50, -0.10; p = 0.04) were significantly
      different statistically. The results for LOS for all patients, LOS for discharged
      patients, ED volume, EMS time at hospital by destination, number of elopements,
      and percent of Boston EMS transports to each hospital revealed no statistically
      significant differences. The difference between the study and control periods for
      mean EMS to hospital time, at-hospital time, and incident entry to arrival was a
      maximum of 0.6 minutes. The vast majority of EMS respondents to an online survey
      believed that the "no diversion" policy should be made routine practice.
      CONCLUSIONS: The LOS for admitted patients decreased by 18 minutes, and the
      number of admissions increased by 1.5 patients per day during the study period.
      The "no diversion" policy resulted in minimal changes in EMS efficiency and
      operations. Diversion was temporarily eliminated in a major city without
      significant detrimental changes in ED, hospital, or EMS efficiency.

PMID- 21888733
TI  - Evaluation of success rate and access time for an adult sternal intraosseous
      device deployed in the prehospital setting.
AB  - INTRODUCTION: Access to the vascular system of the critically ill or injured
      adult patient is essential for resuscitation. Whether due to trauma or disease,
      vascular collapse may delay or preclude even experienced medical providers from
      obtaining standard intravenous (IV) access. Access to the highly vascular
      intramedullary space of long bones provides a direct link to central circulation.
      The sternum is a thin bone easily identified by external landmarks that contains
      well-vascularized marrow. The intraosseous (IO) route rapidly and reliably
      delivers fluids, blood products, and medications. Resuscitation fluids
      administered by IV or IO achieve similar transit times to central circulation.
      The FAST-1 Intraosseous Infusion System is the first FDA-approved mechanical
      sternal IO device. The objectives of this study were to: (1) determine the
      success rate of FAST-1 sternal IO device deployment in the prehospital setting;
      (2) compare the time of successful sternal IO device placement to published data
      regarding time to IV access; and (3) describe immediate complications of sternal
      IO use. METHODS: All paramedics in the City of Portsmouth, Virginia were trained
      to correctly deploy the FAST-1 sternal IO device during a mandatory education
      session with the study investigators. The study subjects were critically ill or
      injured adult patients in cardiac arrest treated by paramedics during a one-year
      period. When a patient was identified as meeting study criteria, the paramedic
      initiated standard protocols; the FAST-1 sternal IO was substituted for the
      peripheral IV to establish vascular access. Time to deployment was measured and
      successful placement was defined as insertion of the needle, with subsequent
      aspiration and fluid flow without infiltration. RESULTS: Over the one-year
      period, paramedics attempted 41 FAST-1 insertions in the pre-hospital setting.
      Thirty (73%) of these were placed successfully. The mean time to successful
      placement was 67 seconds for 28 attempts; three of the 31 insertions did not have
      times recorded by the paramedic. Paramedics listed the problems with FAST-1
      insertion, including: (1) difficulty with adhesive after device placement (3
      events); (2) failure of needles to retract and operator had to pull the device
      out of the skin (2 events); and (3) slow flow (1 event). Emergency department
      physicians noted two events of minor bleeding around the site of device
      placement. CONCLUSION: This is the first study to prospectively evaluate the
      prehospital use of the FAST-1 sternal IO as a first-line device to obtain
      vascular access in the critically ill or injured patient. The FAST-1 sternal IO
      device can be a valuable tool in the paramedic arsenal for the treatment of the
      critically ill or injured patient. The device may be of particular interest to
      specialty disaster teams that deploy in austere environments.

PMID- 21888734
TI  - Retrospective, analytical study of field first aid following the Wenchuan
      Earthquake in China.
AB  - Field first-aid data from the Wenchuan Earthquake in China was analyzed
      retrospectively in order to probe into ways to develop field first-aid operations
      and provide a reference for future emergency rescue. Related documents about the
      Wenchuan Earthquake were collected and reviewed. The state of injury and leading
      causes of death during the disaster were identified. The presnece of emergency
      medical resources on-site after the earthquake was relatively insufficient.
      Deaths mainly were due to cardiopulmonary arrest, severe craniocerebral injury,
      incurable hemorrhagic shock, and crush syndrome that caused multiple organ system
      dysfunction syndrome. Only by strengthening the on-site emergency medical
      resources, speeding-up triage, and equipping responders with professional,
      portable medical equipment, can field first-aid operations be delivered more
      efficiently.

PMID- 21888735
TI  - China's health challenges after the Yushu Earthquake.

PMID- 21888736
TI  - Health impacts of floods.

PMID- 21888737
TI  - Vulnerable populations.

PMID- 21888738
TI  - Ambulance insignias in a turmoil zone.

PMID- 21888739
TI  - Anxious children's ability to generate alternative attributions for ambiguous
      situations.
AB  - BACKGROUND: Cognitive behavioural therapy (CBT) is increasingly being used to
      help children overcome emotional difficulties but its suitability is still a
      matter of debate. AIMS: This study investigated young anxious children's ability
      to generate alternative interpretations for events, a skill thought to be
      important for the effectiveness of CBT. METHOD: A community sample of 60 children
      aged 6-7 years (30 high and 30 low in anxiety) was tested. IQ, developmental
      level and the ability to generate alternative interpretations for ambiguous
      social scenarios were assessed. RESULTS: Both groups generated alternative
      interpretations. However, negative self-referent scenarios were more difficult to
      view from alternative perspectives than positive or other-referent scenarios.
      Correlation analyses suggested that verbal IQ was partially associated with this
      skill in both groups, while developmental level was most important in the high
      anxious group. A "personalizing" bias was found in the negative responses of both
      groups. CONCLUSIONS: It is concluded that young children, whether anxious or not,
      do possess the ability to complete one skill thought important in CBT. While
      difficulty with negative self-referent scenarios and personalizing seem to be
      normative in the sample, those most "at risk" who also have relatively lower
      developmental levels may find the task particularly difficult.

PMID- 21888740
TI  - Urinary excretion of in vivo 13C-labelled milk oligosaccharides in breastfed
      infants.
AB  - Recent observations indicate that human milk oligosaccharides (HMO) are involved
      in a variety of physiological processes in infants. Their metabolic fate,
      however, is virtually unknown. We investigated metabolic aspects in infants after
      endogenous 13C-labelling of HMO. An oral bolus of natural and 13C-labelled
      galactose (Gal; 23 g Gal+4 g 13C-Gal) was given to ten lactating women. Aliquots
      of milk at each nursing as well as breath samples from the mothers and urine from
      their infants were collected over 36 h. The 13C-enrichment of HMO and their renal
      excretion was determined by isotope ratio-MS; characterisation was achieved by
      fast atom bombardment-MS. After the Gal bolus was given, an immediate 13C
      enrichment in milk and in infants' urine was observed which lasted 36 h. Mass
      spectrometric analysis of 13C-enriched urinary fractions confirmed the excretion
      of a variety of neutral and acidic HMO without metabolic modification of their
      structures. Components with glucose split off at the reducing end were also
      detectable. Quantitative data regarding the infants' intake of lacto-N-tetraose
      and its monofucosylated derivative lacto-N-fucopentaose II ranged from 50 to 160
      mg with each suckling, respectively; renal excretion of both components varied
      between 1 and 3 mg/d. Since the intake of individual HMO by the infants was in
      the range of several hundred mg per suckling, i.e. several g/d, and some of these
      components were excreted in mg amounts as intact HMO with the infants' urine, not
      only local but also systemic effects might be expected.

PMID- 21888741
TI  - Changing images, changing visions, changing practices.

PMID- 21888742
TI  - Case report: nodular fasciitis of the parotid region.
AB  - OBJECTIVE: To demonstrate the clinical and histopathological features of nodular
      fasciitis in the parotid region. CASE REPORT: A 24-year-old man presented with a
      palpable mass in the superior border of the parotid gland. The mass was firm and
      immobile, with a smooth surface. Fine needle aspiration cytology revealed
      proliferating fibroblasts, macrophages and adipocytes among the blood cells.
      Although a superficial parotidectomy was initially planned, a total excision was
      performed, as the mass was observed to be located in the periphery of the parotid
      tissue. Nodular fasciitis was diagnosed, based on the results of
      immunohistochemical analysis. CONCLUSION: Nodular fasciitis very rarely occurs in
      the parotid region. These lesions grow quickly, and may be misdiagnosed as
      sarcoma. Trauma may play a role in their aetiology. Total excision is adequate as
      treatment.

PMID- 21888743
TI  - Could Helicobacter pylori play a role in the aetiopathogenesis of
      tympanosclerosis?
AB  - AIM: The aetiology of tympanosclerosis is not yet clear. This prospective,
      controlled, clinical study investigated the relationship between Helicobacter
      pylori and tympanosclerosis aetiology. MATERIALS AND METHODS: The study included
      14 patients with tympanosclerosis and 26 with other forms of chronic otitis
      media. All patients underwent surgery for chronic otitis media. Mucosal biopsies
      were taken, and examined for H pylori using the Campylobacter-Like Organism (CLO)
      test. RESULTS: Tympanoplasty was performed in 29 patients (72.5 per cent),
      radical mastoidectomy in eight (20 per cent) and myringoplasty in three (7.5 per
      cent). The presence of H pylori was tested in all tympanosclerosis biopsies, but
      in only 26.9 per cent of biopsies from other forms of chronic otitis media. A
      statistically significant difference in H pylori presence was found (p <= 0.01).
      CONCLUSION: This study represents a preliminary investigation of the association
      between H pylori and tympanosclerosis development.

PMID- 21888744
TI  - An unusual presentation of aggressive epithelial-myoepithelial carcinoma of the
      nasal cavity with high-grade histology.
AB  - BACKGROUND: Epithelial-myoepithelial carcinoma is an uncommon, low-grade
      carcinoma that generally occurs in the salivary glands. A few cases of epithelial
      myoepithelial carcinoma arising in the nasal cavity have been reported. We
      describe a unique case of aggressive epithelial-myoepithelial carcinoma in the
      nasal cavity. CASE REPORT: A 36-year-old woman presented with a mass in her left
      nasal cavity. Histopathological evaluation revealed it to be an epithelial
      myoepithelial carcinoma with overt nuclear atypia, frequent mitoses and necrosis.
      The tumour recurred in the contralateral nasal cavity 15 months following primary
      excision. Medial maxillectomy and radiation therapy were performed. Seven-month
      follow up revealed extensive bone metastases. CONCLUSION: We report a rare case
      of aggressive epithelial-myoepithelial carcinoma in the nasal cavity, with high
      grade histology.

PMID- 21888745
TI  - Serum levels of interleukins 4 and 10 in head and neck squamous cell carcinoma.
AB  - OBJECTIVE: There is currently controversy over the association between serum
      interleukin-4 and -10 levels and head and neck squamous cell carcinoma in
      patients of different ethnicity. This study aimed to investigate serum levels of
      these cytokines in Iranian patients with this pathology, and to analyse
      correlations with tumour location and tumour stage at diagnosis. DESIGN: Serum
      cytokines levels were quantified using commercial enzyme-linked immunosorbent
      assays. SUBJECTS: Study groups comprised 93 untreated patients and 53 healthy
      donors. RESULTS: Serum interleukin-4 levels were significantly increased in
      patients compared with controls (p < 0.000), but were not significantly
      associated with tumour stage. Serum interleukin-10 levels were not raised in
      patients, nor associated with tumour stage. CONCLUSION: Serum levels of
      interleukin-4, but not -10, were increased in Iranian head and neck squamous cell
      carcinoma patients. These data do not support an association of these cytokines
      with tumour progression; this is consistent with previous findings.

PMID- 21888746
TI  - Bilateral cochlear implantation in a patient with petrous bone cholesteatoma in
      the only hearing ear: case report.
AB  - OBJECTIVE: We report a case of successful cochlear implantation in a patient with
      petrous bone cholesteatoma in the only hearing ear. CASE REPORT: A 63-year-old
      man presented with a four-year history of right-sided, progressive hearing loss
      in his only hearing ear. Computed tomography and magnetic resonance imaging
      revealed a right supralabyrinthine petrous bone cholesteatoma, with erosion of
      the superior semicircular canal and the roof of the internal auditory canal. Due
      to the high risk of post-operative right-sided deafness, we decided first to
      perform left cochlear implantation. Five months later, the patient had a 40 per
      cent score for open-set two-syllable word recognition and an 85 per cent score
      for sentence recognition. Given these good performances, we decided to eradicate
      the cholesteatoma via a translabyrinthine approach, with insertion of a second
      cochlear implant, as a single-stage procedure. A successful outcome was achieved.
      CONCLUSION: Cochlear implantation can be an effective method of hearing
      rehabilitation in patients with petrous bone cholesteatoma, following total
      eradication of disease, if the cochlea remains intact. To our best knowledge,
      this is the first English language report of cochlear implantation in a patient
      with petrous bone cholesteatoma.

PMID- 21888747
TI  - A rare angiosarcoma: retiform haemangioendothelioma.
AB  - OBJECTIVE: We report the case of a rare angiosarcoma, retiform
      haemangioendothelioma, in an 18-year-old young man, which presented as a
      recurrent ulcerating lesion of the left pinna. METHOD: Case report and literature
      review of retiform haemangioendothelioma. This is a low grade angiosarcoma with a
      high local recurrence rate and low metastasis rate, and was first described in
      1994 by Calonje et al. RESULTS: This patient represents only the third report of
      lymph node metastasis in a case of retiform haemangioendothelioma. To date, 31
      cases of the tumour have been reported. Histological diagnosis of this group of
      vascular neoplasms can be challenging, as their histopathological appearance is
      intermediate between haemangioma and angiosarcoma. CONCLUSION: Surgical excision
      remains the primary treatment modality, with adjuvant radiotherapy recommended in
      patients with large tumour size, local recurrence and lymph node metastasis, as
      seen in this case.

PMID- 21888748
TI  - Management of vascular complications of head and neck cancer.
AB  - BACKGROUND: Major vascular complications in patients with head and neck cancer
      have previously been thought of as terminal events. However, it is now possible
      to intervene in many situations, with benefits for quality of life as well as
      survival. Endovascular techniques have reduced morbidity and mortality in many
      situations, both emergency and elective. METHOD: We describe the techniques that
      can be employed in such situations, and present illustrative case reports. Life
      threatening haemorrhage, carotid compression and radiation-induced carotid
      stenosis are all discussed. CONCLUSION: It is possible to predict where
      complications may arise, and to take prophylactic steps to allow treatment to
      continue. Early intervention can reduce both morbidity and mortality in this high
      risk patient group.

PMID- 21888749
TI  - Hot water irrigation as treatment for intractable posterior epistaxis in an out
      patient setting.
AB  - The management of intractable posterior epistaxis is challenging for any
      physician. Nasal packing, often combined with use of an endonasal balloon system,
      is painful for the patient, and torturous to maintain for two to three days. If
      conservative treatment fails, the most commonly used treatment options are
      currently invasive procedures such as endoscopic coagulation of bleeding
      arteries, external ligation and, rarely, embolisation. This paper describes a
      simple, non-invasive technique of treating posterior epistaxis with hot water
      irrigation. Technical information is presented, and the benefits of the method
      are discussed.

PMID- 21888750
TI  - The making of a career: Joseph Toynbee's first steps in otology.
AB  - Joseph Toynbee (1815-1866) is considered one of the fathers of modern otology. He
      spent his whole life in London, studying and describing the anatomy and pathology
      of the main diseases of the ear. This paper presents some of the motivations
      behind Toynbee's decision to specialise in otology, by examining several of his
      letters published under the signature 'J. T.' in The Lancet between 1838 and
      1839. Frustrated by the weakened state of aural surgery in Britain, and by the
      popularity of several 'quacks aurists' (including John Harrison Curtis, William
      Wright and Alexander Turnbull), Toynbee insisted that the study of the ear needed
      to distance itself from quackery and rebuild itself upon a scientific foundation.
      This paper evaluates several exchanges between Toynbee and Curtis, Wright and
      Turnbull.

PMID- 21888751
TI  - Fellowship with professor W P R Gibson in otology and cochlear implantation,
      Sydney, Australia, July to December 2010.

PMID- 21888753
TI  - 'Flaccid neoglottis' following supracricoid partial laryngectomy: laryngoscopic
      revision assisted by navigation system.
AB  - OBJECTIVE: Supracricoid partial laryngectomy is a reliable laryngeal preservation
      procedure for tumour stage 2 and selected stage 3 to 4 laryngeal cancers. Of 70
      patients thus treated, two (3 per cent) had 'flaccid neoglottis', i.e. redundant
      mucosa at the inner arytenoid edge which intermittently obstructed the
      neoglottis. We discuss the mechanism and management of this complication. METHOD:
      The two cases are presented. A navigation system was used to assist surgery.
      Neoglottal spatial alteration (specifically cross-sectional area) was assessed
      pre- and post-operatively using three-dimensional computed tomography. Voice was
      also evaluated. RESULTS: Inspiratory stridor and delayed stomal closure were the
      main symptoms. Minimum neoglottal cross-sectional area was smaller in case one
      than in non-affected patients. Both patients had relatively rougher and breathier
      voices, but had adapted well to this. CONCLUSION: Flaccid neoglottis is mainly
      due to excessive anterior retraction of residual laryngeal mucosa and to
      excessive mucosal pliability with age. A navigation system was useful for
      confirmation, but the potential for incorrect image recognition should be kept in
      mind. Flaccid neoglottis was treatable, with improved laryngeal function.

PMID- 21888752
TI  - Structural characteristics of septal cartilage and mucoperichondrium.
AB  - AIM: During nasal septum surgery, elevation of mucoperichondrium from the
      anterior nasal septum may be more difficult than from the medial and posterior
      septum. This study aimed to evaluate any histological structural differences
      between the anterior and posterior nasal septum cartilage, mucoperichondrium and
      intervening tissue. MATERIAL AND METHOD: Unilateral mucoperichondrial flap
      elevation without infiltration was performed, after nasal tip and dorsum
      decortication, in four patients undergoing open septorhinoplasty. Full-thickness
      samples, including cartilage and mucoperichondrium, were removed from the
      anterior and posterior nasal septum and examined under light and electron
      microscopy. RESULTS: Light microscopy showed no difference between anterior and
      posterior septum specimens regarding perichondrial thickness and subperichondrial
      cell density. Demarcation between cartilage and perichondrium and between
      perichondrium and lamina propria was more regular in the posterior versus the
      anterior septum. Electron microscopy showed no difference in chondroblast
      activity at the two sites. CONCLUSION: The observed tissue demarcation
      irregularities may explain the greater reported difficulty in elevating anterior
      versus posterior nasal septum mucoperichondrium. Immunohistochemical examination
      would further elucidate these interstructural connections.

PMID- 21888754
TI  - Complicated periorbital cellulitis: case report and literature review.
AB  - OBJECTIVE: Periorbital cellulitis secondary to rhinosinusitis is common. However,
      very rarely this can be complicated by a lacrimal gland abscess. We report such a
      case. METHOD: We present a case report and literature review concerning lacrimal
      gland abscess secondary to periorbital cellulitis. RESULTS: Due to the location
      of this condition, prompt assessment and management is vital to avoid potential
      ophthalmological and neurological complications. Our patient failed to respond to
      initial conservative medical treatment, and was subsequently identified as having
      a lacrimal gland abscess, confirmed on contrast-enhanced computed tomography.
      Following definitive surgical treatment, the patient's clinical course improved.
      This case furthers our knowledge of this condition, and adds to the two
      previously reported paediatric cases. CONCLUSION: This case emphasises the
      importance of prompt management, and the fact that failure of clinical
      improvement following orbital decompression should alert the clinician to the
      rare possibility of an associated lacrimal gland abscess. The case also
      emphasises the key role of imaging and a multidisciplinary team approach when
      managing this condition.

PMID- 21888755
TI  - Study of mural paintings using in situ XRF, confocal synchrotron-MU-XRF, MU-XRD,
      optical microscopy, and SEM-EDS--the case of the frescoes from Misericordia
      Church of Odemira.
AB  - In this work, we present the results of an analytical method developed for
      detailed pigment identification, stratigraphy, and degradation of the paint
      layers of mural paintings applied in the study of the 17th century frescoes from
      the Misericordia Church of Odemira (Southwest Portugal). In situ X-ray
      fluorescence spectrometry analyses were performed on three panels of the mural
      paintings and complemented by colorimetric measurements. The different color
      areas were also sampled as microfragments (approx. 1 mm2) that were studied as
      taken or mounted in epoxy resin to expose the different paint layers. The
      microfragments of paint layers and their cross sections were characterized by
      optical microscopy and scanning electron microscopy coupled with energy
      dispersive X-ray spectrometry. Furthermore, elemental analysis was obtained with
      spatially resolved confocal synchrotron radiation MU-X-ray fluorescence
      spectrometry performed at ANKA synchrotron FLUO beamline. Occasionally, phase
      analysis by MU-X-ray diffraction was also performed. Results from the different
      techniques allowed pigment identification and, in some cases, the evaluation of
      color changes due to degradation processes and, considering the Southern Portugal
      geology, the identification of their possible provenance. The pigments used were
      essentially yellow, brown and red ochres, smalt blue, copper green, and black
      earths, probably from local sources.

PMID- 21888756
TI  - Asthma programmes in diverse regions of the world: challenges, successes and
      lessons learnt.
AB  - International surveys have demonstrated that asthma is still underdiagnosed and
      undertreated in many parts of the world. Despite improvements in the standard of
      asthma care delivered in many areas, as evidenced by improved global asthma
      mortality data, much information on projects and programmes undertaken in
      resource-limited regions of the world is not in the public domain. The aim of
      this report is to review projects and programmes in diverse regions around the
      world so that health care providers, planners and consumers may draw on the
      successes, failures and lessons learnt. Such real world experiences may
      contribute to achieving Global Initiative for Asthma goals of asthma control.
      Asthma projects and programmes in Argentina, Australia, Brazil, China, Japan,
      Mexico, Philippines, Russia, South Africa and Turkey were discussed by a group of
      experts in asthma care, the Advancing Asthma Care Network, from their respective
      countries, over a course of three satellite meetings in 2010. Collective analyses
      consistently identified low rates of dissemination and implementation of national
      and international treatment guidelines, low levels of continuing medical
      education and training of primary health care professionals and access and
      distribution of inhaled corticosteroids to be major barriers that are critical to
      the overall success of a national asthma management programme. In the less
      developed asthma programmes, under-recognition and undertreatment further limited
      the success of the programmes. Evidence from well-established national asthma
      management programmes suggests that establishment of a successful programme
      entails a logical progression through specific developmental stages, starting
      with political/stakeholder endorsement and commitment, followed by
      epidemiological evaluation, evaluation of disease burden, evaluation of access to
      care and best therapy, and finally optimisation and maintenance therapy for
      individual patients.

PMID- 21888757
TI  - Efficacy and safety of fluticasone furoate nasal spray in Chinese adult and
      adolescent subjects with intermittent or persistent allergic rhinitis.
AB  - Fluticasone furoate nasal spray (FFNS) is a novel, enhanced-affinity intranasal
      corticosteroid administered for the management of allergic rhinitis (AR). Several
      studies have shown that FFNS at a dose of 110 MUg once daily (o.p.d.) is
      effective in relieving nasal as well as ocular symptoms in adolescents and adults
      with AR. The primary objective of this study was to compare the efficacy and
      safety of FFNS 110 micrograms o.p.d. with matching placebo nasal spray for 2
      weeks in Chinese adult and adolescent subjects with intermittent AR (IAR) or
      persistent AR (PAR). In this multicenter, randomized, double-blind, placebo
      controlled, parallel-group study, patients (adults and adolescents aged >=12
      years with AR) received either FFNS 110 micrograms (n = 181) or placebo (n = 182)
      o.p.d. for 2 weeks. AR was defined according to Allergic Rhinitis and Its Impact
      on Asthma classification. Efficacy measures included reflective total nasal
      symptom score (rTNSS), rhinoscopy score, overall interference in activities of
      daily living (ADL) score, and reflective total ocular symptom score (rTOSS). FFNS
      significantly improved the mean change from baseline in daily rTNSS compared with
      placebo (treatment difference of -1.498, 95% confidence interval [-1.897, 
      1.099]; p < 0.0001). FFNS was also significantly more effective than placebo in
      decreasing rhinoscopy score (treatment difference of -1.3; p < 0.0001) and ADL
      score (treatment difference of -0.4; p < 0.0001). In patients with severe ocular
      symptoms, FFNS showed numerically better treatment effect in reducing daily rTOSS
      than placebo (treatment difference of -0.646; p = 0.0853). FFNS 110 micrograms
      o.p.d. was significantly more effective than placebo in improving nasal symptoms
      in Chinese patients with IAR and PAR. ClinicalTrials.gov registration number:
      NCT01231464.

PMID- 21888758
TI  - Combinatorial approach for fabrication of coatings to control bacterial adhesion.
AB  - Due to the high importance of bacterial infections in medical devices there is an
      increasing interest in the design of anti-fouling coatings. The application of
      substrates with controlled chemical gradients to prevent microbial adhesion is
      presented. We describe here the co-polymerization of poly(ethylene glycol)
      dimethacrylate with a hyperbranched multimethacrylate (H30MA) using a chemical
      gradient generator; and the resulting films were characterized with respect to
      their ability to serve as coating for biomedical devices. The photo-polymerized
      materials present special surface properties due to the hyperbranched structure
      of H30MA and phase separation at specific concentrations in the PEGDM matrix.
      This approach affords the investigation of cell response to a large range of
      different chemistries on a single sample. Two bacterial strains commonly
      associated with surgical site infections, Escherichia coli and Pseudomonas
      aeruginosa, have been cultured on these substrates to study their attachment
      behaviour. These gradient-coated samples demonstrate less bacterial adhesion at
      higher concentrations of H30MA, and the adhesion is substantially affected by the
      extent of surface phase segregation. 

PMID- 21888759
TI  - In vitro biocompatibility evaluation of novel urethane-siloxane co-polymers based
      on poly(epsilon-caprolactone)-block-poly(dimethylsiloxane)-block-poly(epsilon
      caprolactone).
AB  - Novel polyurethane co-polymers (TPUs), based on poly(epsilon-caprolactone)-block
      poly(dimethylsiloxane)-block-poly(epsilon-caprolactone) (PCL-PDMS-PCL) as soft
      segment and 4,4'-methylenediphenyl diisocyanate (MDI) and 1,4-butanediol (BD) as
      hard segment, were synthesized and evaluated for biomedical applications. The
      content of hard segments (HS) in the polymer chains was varied from 9 to 63 wt%.
      The influence of the content and length of the HS on the thermal, surface,
      mechanical properties and biocompatibility was investigated. The structure,
      composition and HS length were examined using (1)H- and quantitative (13)C-NMR
      spectroscopy. DSC results implied that the synthesized TPUs were semicrystalline
      polymers in which both the hard MDI/BD and soft PCL-PDMS-PCL segments
      participated. It was found that an increase in the average HS length (from 1.2 to
      14.4 MDI/BD units) was accompanied by an increase in the crystallinity of the
      hard segments, storage moduli, hydrophilicity and degree of microphase separation
      of the co-polymers. Depending on the HS content, a gradual variation in surface
      properties of co-polymers was revealed by FT-IR, AFM and static water contact
      angle measurements. The in vitro biocompatibility of co-polymers was evaluated
      using the endothelial EA.hy926 cell line and protein adsorption on the
      polyurethane films. All synthesized TPUs adsorbed more albumin than fibrinogen
      from multicomponent protein mixture, which may indicate biocompatibility. The
      polyurethane films with high HS content and/or high roughness coefficient exhibit
      good surface properties and biocompatible behavior, which was confirmed by non
      toxic effects to cells and good cell adhesion. Therefore, the non-cytotoxic
      chemistry of the co-polymers makes them good candidates for further development
      as biomedical implants. 

PMID- 21888760
TI  - Efficient bone regeneration induced by bone morphogenetic protein-2 released from
      apatite-coated collagen scaffolds.
AB  - Bone morphogenetic proteins (BMPs) are the most potent osteoinductive growth
      factors. Clinically utilized BMP-2 uses a type-I collagen scaffold as a carrier.
      Here we hypothesized that an apatite coating on a type-I collagen scaffold would
      prolong the BMP-2 release period and enhance bone regeneration in calvarial
      defects in mice. Apatite coating was achieved by incubating collagen scaffolds in
      simulated body fluid. BMP-2 release kinetics and bioactivity were evaluated by
      enzyme-linked immunosorbent assay and alkaline phosphatase activity measurement
      of cultured osteoblasts. Computed tomography and histomorphometry were performed
      eight weeks after various doses of BMP-2 were delivered to mouse calvarial
      defects using either non-modified or apatite-coated collagen scaffolds. Apatite
      coated collagen scaffolds released 91.8 +/- 11.5% of the loaded BMP-2 over 13
      days in vitro, whereas non-modified collagen scaffolds released 98.3 +/- 2.2%
      over the initial one day. The in vivo study showed that BMP-2 delivery with
      apatite-coated collagen scaffolds resulted in a significantly greater bone
      formation area and higher bone density than that with non-modified collagen
      scaffolds. This study suggests that simple apatite coating on collagen scaffolds
      can enhance the bone regeneration efficacy of BMP-2 released from collagen
      scaffolds. 

PMID- 21888761
TI  - Enhanced guided bone regeneration by asymmetrically porous PCL/pluronic F127
      membrane and ultrasound stimulation.
AB  - Recently, we developed a novel method for fabricating a guided bone regeneration
      (GBR) membrane with an asymmetrical pore structure and hydrophilicity by an
      immersion precipitation method. Results from an animal study, in a cranial defect
      model in rats, indicated that the unique asymmetrically porous GBR membrane would
      provide a good environment for bone regeneration. In the present study, we
      applied low intensity pulsed ultrasound as a simple and non-invasive stimulus to
      an asymmetrically porous polycaprolactone (PCL)/Pluronic F127 GBR membrane
      implanted site transcutaneously in rats to investigate the feasibility of using
      ultrasound to stimulate enhanced bone regeneration through the membrane. It was
      observed that the ultrasound-stimulated PCL/F127 GBR membrane group had much
      faster bone regeneration behavior than a PCL/F127 membrane group w/o ultrasound
      or a control group (w/o membrane and ultrasound). The greater bone regeneration
      behavior in the GBR membrane/ultrasound group may be caused by a synergistic
      effect of the asymmetrically porous PCL/F127 membrane with unique properties
      (selective permeability, hydrophilicity and osteoconductivity), and the
      stimulatory effect of ultrasound (induction of angiogenesis and osteogenesis of
      cells). 

PMID- 21888762
TI  - Potential of a PLA-PEO-PLA-based scaffold for skin tissue engineering: in vitro
      evaluation.
AB  - This study aimed to investigate the in vitro behaviour of porous degradable
      scaffolds of the PLA-PEO-PLA-type designed prior to in vivo evaluation for skin
      tissue engineering. Two tri-block co-polymers were synthesized from PEO and DL
      lactide and their degradation was studied under conditions that mimic a cutaneous
      wound environment. 3-D porous scaffolds with interconnected pores were fabricated
      using the salt leaching method and characterized by ESEM and Hg porosimetry. The
      degrading action of gamma sterilization was studied on the co-polymers. The less
      degraded one was selected to make porous scaffolds on which human dermal
      fibroblasts and human epidermal keratinocytes were cultured. The capacity of such
      scaffolds to act as a dermal equivalent was also considered. Colonization by
      human dermal fibroblasts was shown after hematoxylin staining and the production
      of major proteins normally found in the extracellular matrix was assessed by
      Western blotting of protein extracts. Finally, a skin substitute was generated by
      seeding human keratinocytes on the dermal equivalent and a new epidermis was
      characterized by using immuno-histological staining. Results show that gamma
      sterilization and that degradation under conditions that mimic skin wound healing
      were acceptable. The fact that fibroblasts produce extracellular matrix and that
      keratinocytes generated an epidermal barrier argues in favour of the interest of
      this type of porous scaffold for skin reconstruction. 

PMID- 21888763
TI  - The role of stereo vision in visual-vestibular integration.
AB  - Self-motion through an environment stimulates several sensory systems, including
      the visual system and the vestibular system. Recent work in heading estimation
      has demonstrated that visual and vestibular cues are typically integrated in a
      statistically optimal manner, consistent with  Maximum Likelihood Estimation
      predictions. However, there has been some indication that cue integration may be
      affected by characteristics of the visual stimulus. Therefore, the current
      experiment evaluated whether presenting optic flow stimuli stereoscopically, or
      presenting both eyes with  the same image (binocularly) affects combined visual
      vestibular heading estimates. Participants performed a two-interval forced-choice
      task in which they were asked which of two presented movements was more
      rightward. They were presented with either visual cues alone, vestibular cues 
      alone or both cues combined. Measures of reliability were obtained for both
      binocular and stereoscopic conditions. Group level analyses demonstrated that
      when stereoscopic information was available there was clear evidence of optimal
      integration, yet when only binocular information was  available weaker evidence
      of cue integration was observed. Exploratory individual analyses demonstrated
      that for the stereoscopic condition 90% of participants exhibited optimal
      integration, whereas for the binocular condition only 60% of participants
      exhibited results consistent with optimal  integration. Overall, these findings
      suggest that stereo vision may be important for self-motion perception,
      particularly under combined visual-vestibular conditions.

PMID- 21888764
TI  - Effects of sound on the tactile perception of roughness in peri-head space.
AB  - The aim of this study is to investigate whether or not spatial congruency between
      tactile and auditory stimuli would influence the tactile roughness discrimination
      of stimuli presented to the fingers or cheeks. In the experiment, when abrasive
      films were passively presented to the participants,  white noise bursts were
      simultaneously presented from the same or different side, either near or far from
      the head. The results showed that when white noise was presented from the same
      side as the tactile stimuli, especially from near the head, the discrimination
      sensitivity on the cheeks  was higher than when sound was absent or presented
      from a different side. A similar pattern was observed in discrimination by the
      fingers but it was not significant. The roughness discrimination by the fingers
      was also influenced by the presentation of sound close to the head, but
      significant  differences between conditions with and without sounds were observed
      at the decisional level. Thus, the spatial congruency between tactile and
      auditory information selectively modulated the roughness sensitivity of the skin
      on the cheek, especially when the sound source was close to the head.

PMID- 21888765
TI  - Oxidative stress in Rett syndrome: natural history, genotype, and variants.
AB  - OBJECTIVES: Rett syndrome (RTT) is an X-linked autism spectrum disorder caused by
      mutations in the MeCP2 gene in the great majority of cases. Evidence suggests a
      potential role of oxidative stress (OS) in its pathogenesis. Here, we
      investigated the potential value of OS markers (non-protein-bound iron (NPBI) and
      F2-isoprostanes (F2-IsoPs)) in explaining natural history, genotype-phenotype
      correlation, and clinical heterogeneity of RTT, and gauging the response to omega
      3 polyunsaturated fatty acids (omega-3 PUFAs). METHODS: RTT patients (n=113) and
      healthy controls were assayed for plasma NPBI and F2-IsoPs, and intraerythrocyte
      NPBI. Forty-two patients with typical RTT were randomly assigned to omega-3 PUFAs
      supplementation for 12 months. NPBI was measured by HPLC and F2-IsoPs using a gas
      chromatography/negative ion chemical ionization tandem mass spectrometry (GC/NICI
      MS/MS) technique. RESULTS: F2-IsoPs were significantly higher in the early stages
      as compared with the late natural progression of classic RTT. MeCP2 mutations
      related to more severe phenotypes exhibited higher OS marker levels than those of
      milder phenotypes. Higher OS markers were observed in typical RTT and early
      seizure variant as compared with the preserved speech and congenital variants.
      Significant reduction in OS markers levels and improvement of severity scores
      were observed after omega-3 PUFAs supplementation. DISCUSSION: OS is a key
      modulator of disease expression in RTT.

PMID- 21888766
TI  - The bacterial redox signaller pyocyanin as an antiplasmodial agent: comparisons
      with its thioanalog methylene blue.
AB  - The quorum sensor and signalling molecule pyocyanin (PYO) contributes
      significantly to the pathophysiology of Pseudomonas aeruginosa infections.
      Comparison to phenothiazine drugs suggests that the antimalarial compound
      methylene blue (MB) can be regarded as a sulfur analog of PYO. This working
      hypothesis would explain why the synthetic drug MB behaves as a compound shaped
      in biological evolution. Here we report on redox-associated biological and
      biochemical properties of PYO in direct comparison to its synthetic analog MB. We
      quantitatively describe the reactivity of both compounds toward cellular
      reductants, the reactivity of their reduced leuco-forms towards O2, and their
      interactions with FAD-containing disulfide reductases. Furthermore, the
      interaction of PYO with human glutathione reductase was studied in structural
      detail by x-ray crystallography, showing that a single PYO molecule binds to the
      intersubunit cavity of the enzyme. Like MB, also PYO was also found to be active
      against blood schizonts of the malaria parasite P. falciparum in vitro.
      Furthermore, both compounds were active against the disease transmitting
      gametocyte forms of the parasites, which was systematically studied in vitro. As
      shown for mice, PYO is too toxic to be used as a drug. It may, however, have
      antimalarial activity in numerous human patients with concomitant Pseudomonas
      infections. MB, in contrast to PYO, is well tolerated and represents a promising
      agent for MB-based combination therapies against malaria. Current and future
      clinical studies can be guided by the comparisons between MB and PYO reported
      here. Additionally, it is of interest to study if and to what extent the
      protection from malaria in patients with cystic fibrosis or with severe wound
      infections is based on PYO produced by Pseudomonas species.

PMID- 21888767
TI  - Aminoguanidine and N-acetyl-cysteine supress oxidative and nitrosative stress in
      EAE rat brains.
AB  - Experimental autoimmune encephalomyelitis (EAE) is a well-established animal
      model of human multiple sclerosis (MS). We have evaluated the role of oxidative
      and nitrosative stress, as the causal factors in the development of EAE,
      responsible for the damage of cardinal cellular components, such as lipids,
      proteins and nucleic acids, resulting in demyelination, axonal damage, and
      neuronal death. EAE was induced in female Sprague-Dawley rats, 3 months old
      (300+/-20 g), by immunization with myelin basic protein in combination with
      Complete Freund's adjuvant (CFA). The animals were divided into seven groups:
      control, EAE, CFA, EAE+aminoguanidine (AG), AG, EAE+N-acetyl-L-cysteine (NAC) and
      NAC. The animals were sacrificed 15 days after EAE induction, and the levels of
      nitrosative and oxidative stress were determined in 10% homogenate of the whole
      encephalitic mass. In EAE rats, brain NO production and MDA level were
      significantly increased (P<0.001) compared to the control values, whereas AG and
      NAC treatment decreased both parameters in EAE rats compared to EAE group
      (P<0.001). Glutathione (GSH) was reduced (P<0.001) in EAE rats in comparison with
      the control and CFA groups, but increased in EAE+AG and EAE+NAC group compared to
      the EAE group (P<0.01). Superoxide dismutase (SOD) activity was significantly
      decreased (P<0.001) in the EAE group compared to all other experimental groups.
      The clinical expression of EAE was significantly decreased (P<0.05) in the EAE
      groups treated with AG and NAC compared to EAE rats, during disease development.
      The obtained results prove an important role of oxidative and nitrosative stress
      in the pathogenesis of EAE, whereas AG and NAC protective effects offer new
      possibilities for a modified combined approach in MS therapy.

PMID- 21888769
TI  - Tyr740 and Tyr751 residues of platelet-derived growth factor beta receptor are
      responsible for the redox regulation of phosphatase and tensin homolog in the
      cells stimulated with platelet-derived growth factor.
AB  - Exposure of cells to hydrogen peroxide or platelet-derived growth factor (PDGF)
      induced Akt phosphorylation and oxidation of phosphatase and tensin homolog
      (PTEN). The Cys124 and Cys71 residues of PTEN were critical for the formation of
      a disulfide bond and the intermediate glutathionylation in the process of
      reduction of the disulfide bond. To determine which specific tyrosine residues of
      the PDGF beta receptor (PDGFbetaR) is involved in PDGF-induced PTEN oxidation and
      Akt phosphorylation, we investigated a kinase activity-deficient mutant and
      PDGFbetaR mutants where the tyrosine residues in the binding site for
      phosphoinositide 3-kinase (PI3K), GTPase-activating protein of Ras, Src homology
      2 domain containing protein-tyrosine phosphatase-2, and phospholipase C-1 were
      replaced by Phe. Both PTEN oxidation and Akt phosphorylation did not occur in
      response to PDGF in the kinase-deficient mutant and in the PDGFbetaR mutant with
      a mutation in the PI3K binding site (Tyr740 and Tyr751). Thus, the kinase
      activity and the constituent Tyr740 and Tyr751 residues of PDGFbetaR in the cells
      stimulated with PDGF are responsible for the oxidation of PTEN and the Akt
      phosphorylation.

PMID- 21888768
TI  - N-acetylcysteine protects pancreatic islet against glucocorticoid toxicity.
AB  - OBJECTIVES: Reactive oxygen species (ROS) are involved in many physiological and
      pathological processes. In the present study, we analysed whether the synthetic
      glucocorticoid dexamethasone induces oxidative stress in cultured pancreatic
      islets and whether the effects of dexamethasone on insulin secretion, gene
      expression, and viability can be counteracted by concomitant incubation with N
      acetylcysteine (NAC). METHODS: ROS production was measured by dichlorofluorescein
      (DCFH-DA) assay, insulin secretion by radioimmunoassay, intracellular calcium
      dynamics by fura-2-based fluorescence, gene expression by real-time polymerase
      chain reaction analyses and cell viability by the MTS assay. RESULTS:
      Dexamethasone (Dexa) increased ROS production and decreased glucose-stimulated
      insulin secretion after 72 hours incubation. Intracellular ROS levels were
      decreased and the insulin secretion capacity was recovered by concomitant
      treatment with Dexa+NAC. The total insulin content and intracellular Ca2+ levels
      were not modulated in either Dexa or Dexa+NAC groups. There was a decrease in the
      NAD(P)H production, used as an indicator of viability, after dexamethasone
      treatment. Concomitant incubation with NAC returned viability to control levels.
      Dexa also decreased synaptotagmin VII (SYT VII) gene expression. In contrast, the
      Dexa+NAC group demonstrated an increased expression of SYT VII compared to
      controls. Surprisingly, treatment with NAC decreased the gene expression of the
      antioxidant enzyme copper zinc superoxide dismutase soluble. DISCUSSION: Our
      results indicate that dexamethasone increases ROS production, decreases
      viability, and impairs insulin secretion in pancreatic rat islets. These effects
      can be counteracted by NAC, which not only decreases ROS levels but also
      modulates the expression of genes involved in the secretory pathway and those
      coding for antioxidant enzymes.

PMID- 21888771
TI  - Preventing oral disease.

PMID- 21888772
TI  - Periodontal disease and chronic obstructive pulmonary disease.
AB  - The purpose of Linking Research to Clinical Practice is to present evidence based
      information to clinical dental hygienists so that they can make informed
      decisions regarding patient treatment and recommendations. Each issue will
      feature a different topic area of importance to clinical dental hygienists with A
      BOTTOM LINE to translate the research findings into clinical application.

PMID- 21888773
TI  - Bariatric surgery and implications for oral health: a case report.
AB  - PURPOSE: A case representative of issues dental practitioners may face when
      providing care to patients with a history of bariatric surgery is reviewed. Meta
      analysis shows that, following bariatric surgery, 43 to 79% of diabetes,
      hyperlipidemia and hypertension in patients resolved to normal levels or no
      longer required therapy. However, bariatric surgery side effects have
      implications for oral health, including nutrient deficiencies impacting healing
      of oral tissues and gastroesophageal reflux, resulting in tooth erosion. Patients
      who have undergone bariatric surgery are seen with increasing frequency in dental
      offices and dental professionals need to be familiar with the challenges these
      patients present.

PMID- 21888774
TI  - Use of social networking for dental hygiene program recruitment.
AB  - PURPOSE: Social networking has become a popular and effective means of
      communication used by students in the millennial generation. Academic admissions
      officers are beginning to utilize social networking methods for recruitment of
      students. However, the dental hygiene literature has reported little information
      about the use of social networking for recruitment strategies. This paper
      describes one institutions' process of creating and implementing a social network
      site for prospective and current students.

PMID- 21888775
TI  - Extending oral health care services to underserved children through a school
      based collaboration: part 1: a descriptive overview.
AB  - PURPOSE: The purpose of this report is to describe the process and outcomes of a
      collaborative, comprehensive preventive oral health program between the
      University of Missouri-Kansas City School of Dentistry, the Olathe School
      District and an Extended Care Permit I dental hygienist. The report describes the
      programs collectively working to provide school-based services to disadvantaged
      children in 4 Title I schools using the community collaborative practice oral
      health model and tele-dentistry. METHODS: The "Miles of Smiles" clinic was
      assembled in 4 elementary schools using portable dental equipment. Dental hygiene
      students, supervised by a dental hygiene faculty member with an extended care
      permit, provided comprehensive preventive oral health care to unserved and
      underserved children. RESULTS: Twenty-eight dental hygiene students provided
      prophylaxis, radiographs, sealants, fluoride varnish, oral health education and
      nutritional counseling to 339 children in the Miles of Smiles clinic during the
      2008 to 2009 academic year. Sixty-three percent of children had decay and were
      referred to a dentist. Upon re-evaluating at the end of the school year, 11% had
      begun the transition process of seeking restorative care at a safety net clinic
      or from a local dentist. CONCLUSION: School based oral health models, using
      dental hygienists with expanded scopes of practice to provide preventive oral
      health services and referrals, can serve as one approach to overcoming barriers
      and reaching vulnerable children that desperately need oral health care. However,
      transitioning children outside of their school to a safety net clinic or local
      dentist to receive restorative care was found to be problematic.

PMID- 21888777
TI  - Evaluation of educational material for tobacco prevention and cessation used in
      west virginia university dental programs.
AB  - PURPOSE: Patient educational materials for tobacco prevention and cessation are
      crucial for dental and dental hygiene education. The programs rely upon written
      educational material for tobacco prevention and cessation, referred to as empty
      packs (EMT-PCs), which students distribute to the community during face to face
      or community-based oral health and tobacco awareness programs. The public often
      does not understand the EMT-PC that is received due to the high level of
      complexity and readability of the documents. The authors conducted a study to
      investigate the EMT-PCs available and used in the West Virginia University School
      of Dentistry programs. It was hypothesized that they were readable at the eighth
      grade or lower level, used appropriate font, had good production quality, had
      appropriate content and were current. METHODS: The authors selected 40 EMT-PCs
      used in tobacco prevention and cessation programs. Initially, the Fry Readability
      Formula was applied. Next, they evaluated the font, language, production quality,
      appropriateness for the target audience and recency of the document based upon
      its copyright or revision within the previous 5 years. RESULTS: The average
      reading level of the EMT-PCs was grade 6.67 (range 2-17+). The average font size
      was 13.8 (range 8-14) and the average date of production or revision was 2003.
      Patient educational materials for the general public should be produced at or
      below the eighth grade reading level, have a 12 point or larger font size and be
      produced or updated within the previous 5 years. CONCLUSION: The hypothesis was
      supported in that EMT-PCs distributed in the West Virginia University School of
      Dentistry programs met the criteria for appropriate grade level, font, quality
      and content, while the average copyright or revision date was 5.9 years, slightly
      beyond the recommended 5 years. Effective EMT-PCs should be readable and
      appropriately directed to the target audiences. Dental professionals have access
      to current, quality tobacco cessation documents and should be aware of the need
      to evaluate the documents for appropriate literacy levels for various groups.

PMID- 21888776
TI  - Extending oral health care services to underserved children through a school
      based collaboration: part 2: the student experience.
AB  - PURPOSE: The purpose of this study was to examine the experiences of dental
      hygiene students providing services to unserved and underserved children in a
      school-based collaboration between a dental school, school district and Extended
      Care Permit I (ECP-I) dental hygienist in Kansas. METHODS: Following
      comprehensive preventive oral health care services to children in 4 schools
      supervised by an ECP-I dental hygienist, 26 senior dental hygiene students
      enrolled in the dental hygiene program at the University of Missouri-Kansas City
      submitted rotation data records and self-reflection journals describing the
      experience. Using the constant comparative method, 3 faculty researchers unitized
      the data by identifying key themes. RESULTS: Data from student reflections was
      aggregated into 5 categories: skill development (46%), awareness (19%), type of
      experience (15%), description of environment/setting (13%) and role model (7%).
      CONCLUSION: Participation in well-designed service learning programs is rewarding
      for students providing the services and works toward developing the skills needed
      to competently care for the changing needs of society. New models of oral health
      care and expanded roles for dental hygienists are providing greater access to
      preventive oral health care in Kansas.

PMID- 21888778
TI  - Improving access to preventive dental services through a school-based dental
      sealant program.
AB  - PURPOSE: The lack of access to preventive dental services, such as dental
      sealants, can be a major barrier to optimal dental health. School-based dental
      sealant programs can serve as programs to improve access to preventive dental
      services. METHODS: This school-based dental sealant program managed by a Boston
      dental school with collaborating partners in the metro west area of Massachusetts
      provides free dental sealants to second grade children. The number of second
      grade children having dental sealants was tracked for 6 school years and compared
      with the Healthy People 2010 objective of 50% of all children aged 8 years to
      have at least 1 dental sealant. RESULTS: From school years 2003 to 2004 through
      2008 to 2009, 1,609 dental screenings were provided for second grade children. Of
      those, 1,189 received dental sealants. To determine whether or not the Healthy
      People 2010 objective was met, the number of children who received dental
      sealants from the school-based program was added to the number of children who
      already had their permanent first molars sealed by their own dentist at the time
      of the dental screening, plus children with sealants per parent report. In total,
      the aggregate second grade enrollment having sealants during the designated
      school years was 54%. CONCLUSION: The specific Healthy People 2010 objective was
      achieved over the designated time period. School-based dental sealant programs
      can help to decrease or eliminate barriers for access to preventive dental
      services by increasing the number of children who receive dental sealants.

PMID- 21888779
TI  - The impact of a continuing education oral health program on providing services
      for young children by dentists, dental hygienists and dental assistants.
AB  - PURPOSE: The purpose of this study was to determine the impact of a 4 hour
      continuing education (CE) program on the oral health knowledge and behaviors of
      dentists, dental hygienists and dental assistants in providing oral health
      services to young children in West Virginia general dental practices. METHODS: A
      free CE program was provided for 92 general dentists, 123 dental hygienists and
      37 dental assistants (n=252) at 4 sites across West Virginia. Participants
      completed a pre- and post-test on topics including the timing of the first dental
      exam, fluorides, xylitol, Alternative Restorative Technique (ART) and their
      practice pattern of caring for children under 3 years old. A 6 month follow-up
      questionnaire was mailed to participants to assess outcomes. RESULTS:
      Participants showed a 22% increase in knowledge from the pre-test to the post
      test (p<0.001) for all questions except for ART, which showed no change. The
      majority of dentists and hygienists (89%) increased their comfort in providing
      services for children under 3 years old. Participants (80%) stated they would
      increase the number of children under 3 years old they examine, yet 6 months
      after the program only 42% responded affirmatively (p<0.001). At the time of the
      program, 62% reported that they currently examine children at 1 year of age, and
      there was no significant change 6 months later. While 54% responded that they
      would contact their local physicians about early oral health care, only 27%
      followed through. CONCLUSION: This program significantly increased the
      participants' knowledge and comfort level for providing infant and toddler oral
      health care. However, it did not motivate most to alter their practice behaviors
      to conform to national best practice guidelines.

PMID- 21888780
TI  - A comparison of millennial dental hygiene student and faculty classroom
      expectations.
AB  - PURPOSE: Research has shown that Millennial students are different than students
      in previous generations. This study compares the expectations of the didactic
      environment of faculty and students in a baccalaureate dental hygiene program.
      Expectations of faculty and students were examined, and comparisons between
      Millennial and non-Millennial students and faculty were made in order to improve
      the educational experience of dental hygiene students. METHODS: Students and
      faculty completed a survey adapted from McCargar's role expectations survey.
      Items were chosen from the survey to cover such areas as technology, group work
      and authority. The survey consisted of a Likert-type scale including strongly
      agree, agree, neutral, disagree and strongly disagree. Data was entered into SPSS
      15.0 database. Scoring on negative questions was reversed so that the score would
      be positive. Individual answers are given the following scoring assignments:
      Strongly Agree (+2), Agree (+1), Neutral (0), Disagree (-1) and Strongly Disagree
      (-2). Scores were added together to create a summative score for each item.
      Descriptive statistics and an unpaired t-test comparing responses were used to
      analyze data. Cronbach's alpha was run to measure the internal consistency of the
      instrument. RESULTS: Twelve faculty and 94 students returned surveys. Students
      felt strongly that copies of course notes should be available online and faculty
      should return emails within 24 hours. Statistically significant differences in
      the expectations of Millennial and non-Millennial students were found in regards
      to issues of authority, community service, attendance and evaluation. The
      majority of significant differences were found between Millennial students and
      faculty. Significant differences were found in interaction, community service,
      technology and homework. CONCLUSION: Faculty should examine the expectations of
      their students and should use the findings to create learning experiences that
      are more effective for students. Expectations change with each generation, and it
      is important to change techniques and methodologies in order to meet the needs of
      current students and the profession.

PMID- 21888781
TI  - Rift Valley Fever Vaccine Development, Progress and Constraints.

PMID- 21888782
TI  - Risk-based estimate of effect of foodborne diseases on public health, Greece.
AB  - The public health effects of illness caused by foodborne pathogens in Greece
      during 1996-2006 was quantified by using publicly available surveillance data,
      hospital statistics, and literature. Results were expressed as the incidence of
      different disease outcomes and as disability-adjusted life years (DALY), a health
      indicator combining illness and death estimates into a single metric. It has been
      estimated that each year ~370,000 illnesses/million inhabitants are likely caused
      because of eating contaminated food; 900 of these illnesses are severe and 3
      fatal, corresponding to 896 DALY/million inhabitants. Ill-defined intestinal
      infections accounted for the greatest part of reported cases and 27% of the DALY.
      Brucellosis, echinococcosis, salmonellosis, and toxoplasmosis were found to be
      the most common known causes of foodborne illnesses, being responsible for 70% of
      the DALY. Overall, the DALY metric provided a quantitative perspective on the
      impact of foodborne illness that may be useful for prioritizing food safety
      management targets.

PMID- 21888783
TI  - Estimating effect of antiviral drug use during pandemic (H1N1) 2009 outbreak,
      United States.
AB  - From April 2009 through March 2010, during the pandemic (H1N1) 2009 outbreak,
      ~8.2 million prescriptions for influenza neuraminidase-inhibiting antiviral drugs
      were filled in the United States. We estimated the number of hospitalizations
      likely averted due to use of these antiviral medications. After adjusting for
      prescriptions that were used for prophylaxis and personal stockpiles, as well as
      for patients who did not complete their drug regimen, we estimated the filled
      prescriptions prevented ~8,400-12,600 hospitalizations (on the basis of median
      values). Approximately 60% of these prevented hospitalizations were among adults
      18-64 years of age, with the remainder almost equally divided between children 0
      17 years of age and adults >65 years of age. Public health officials should
      consider these estimates an indication of success of treating patients during the
      2009 pandemic and a warning of the need for renewed planning to cope with the
      next pandemic.

PMID- 21888784
TI  - Intrahousehold transmission of pandemic (H1N1) 2009 virus, Victoria, Australia.
AB  - To examine intrahousehold secondary transmission of pandemic (H1N1) 2009 virus in
      households in Victoria, Australia, we conducted a retrospective cross-sectional
      study in late 2009. We randomly selected case-patients reported during May-June
      2009 and their household contacts. Information collected included household
      characteristics, use of prevention and control measures, and signs and symptoms.
      Secondary cases were defined as influenza-like illness in household contacts
      within the specified period. Secondary transmission was identified for 18 of 122
      susceptible household contacts. To identify independent predictors of secondary
      transmission, we developed a model. Risk factors were concurrent quarantine with
      the household index case-patient, and a protective factor was antiviral
      prophylaxis. These findings show that timely provision of antiviral prophylaxis
      to household contacts, particularly when household members are concurrently
      quarantined during implementation of pandemic management strategies, delays or
      contains community transmission of pandemic (H1N1) 2009 virus.

PMID- 21888785
TI  - Epidemiologic modeling with FluSurge for pandemic (H1N1) 2009 outbreak,
      Queensland, Australia.
AB  - At the beginning of the pandemic (H1N1) 2009 outbreak, we estimated the potential
      surge in demand for hospital-based services in 4 Health Service Districts of
      Queensland, Australia, using the FluSurge model. Modifications to the model were
      made on the basis of emergent evidence and results provided to local hospitals to
      inform resource planning for the forthcoming pandemic. To evaluate the fit of the
      model, a comparison between the model's predictions and actual hospitalizations
      was made. In early 2010, a Web-based survey was undertaken to evaluate the
      model's usefulness. Predictions based on modified assumptions arising from the
      new pandemic gained better fit than results from the default model. The survey
      identified that the modeling support was helpful and useful to service planning
      for local hospitals. Our research illustrates an integrated framework involving
      post hoc comparison and evaluation for implementing epidemiologic modeling in
      response to a public health emergency.

PMID- 21888786
TI  - Differential effects of pandemic (H1N1) 2009 on remote and indigenous groups,
      Northern Territory, Australia, 2009.
AB  - Pandemic (H1N1) 2009 influenza spread through the Northern Territory, Australia,
      during June-August 2009. We performed 2 cross-sectional serologic surveys on
      specimens from Northern Territory residents, with 445 specimens obtained
      prepandemic and 1,689 specimens postpandemic. Antibody titers were determined by
      hemagglutination inhibition against reference virus A/California/7/2009 on serum
      samples collected opportunistically from outpatients. All specimens had data for
      patients' gender, age, and address, with patients' indigenous status determined
      for 94.1%. Protective immunity (titer >40) was present in 7.6% (95% confidence
      interval [CI] 5.2%-10.1%) of prepandemic specimens and 19.5% (95% CI 17.6%-21.4%)
      of postpandemic specimens, giving a population-standardized attack rate of 14.9%
      (95% CI 11.0%-18.9%). Prepandemic proportion of immune persons was greater with
      increasing age but did not differ by other demographic characteristics.
      Postpandemic proportion of immune persons was greater in younger groups and
      around double in indigenous persons. Postpandemic proportion immune was
      geographically heterogeneous, particularly among remote-living and indigenous
      groups.

PMID- 21888787
TI  - Role of Chlamydia trachomatis in miscarriage.
AB  - To determine the role of Chlamydia trachomatis in miscarriage, we prospectively
      collected serum, cervicovaginal swab specimens, and placental samples from 386
      women with and without miscarriage. Prevalence of immunoglobulin G against C.
      trachomatis was higher in the miscarriage group than in the control group (15.2%
      vs. 7.3%; p = 0.018). Association between C. trachomatis-positive serologic
      results and miscarriage remained significant after adjustment for age, origin,
      education, and number of sex partners (odds ratio 2.3, 95% confidence interval
      1.1-4.9). C. trachomatis DNA was more frequently amplified from products of
      conception or placenta from women who had a miscarriage (4%) than from controls
      (0.7%; p = 0.026). Immunohistochemical analysis confirmed C. trachomatis in
      placenta from 5 of 7 patients with positive PCR results, whereas results of
      immunohistochemical analysis were negative in placenta samples from all 8
      negative controls tested. Associations between miscarriage and
      serologic/molecular evidence of C. trachomatis infection support its role in
      miscarriage.

PMID- 21888788
TI  - Classical bovine spongiform encephalopathy by transmission of H-type prion in
      homologous prion protein context.
AB  - Bovine spongiform encephalopathy (BSE) and BSE-related disorders have been
      associated with a single major prion strain. Recently, 2 atypical, presumably
      sporadic forms of BSE have been associated with 2 distinct prion strains that are
      characterized mainly by distinct Western blot profiles of abnormal protease
      resistant prion protein (PrPres), named high-type (BSE-H) and low-type (BSE-L),
      that also differed from classical BSE. We characterized 5 atypical BSE-H isolates
      by analyzing their molecular and neuropathologic properties during transmission
      in transgenic mice expressing homologous bovine prion protein. Unexpectedly, in
      several inoculated animals, strain features emerged that were highly similar to
      those of classical BSE agent. These findings demonstrate the capability of an
      atypical bovine prion to acquire classical BSE-like properties during propagation
      in a homologous bovine prion protein context and support the view that the
      epidemic BSE agent could have originated from such a cattle prion.

PMID- 21888789
TI  - Increasing incidence of invasive Haemophilus influenzae disease in adults, Utah,
      USA.
AB  - Since the introduction of the Haemophilus influenzae type b vaccine, the
      incidence of invasive H. influenzae type b disease among children has fallen
      dramatically, but the effect on invasive H. influenzae disease among adults may
      be more complex. In this population-based study we examined the epidemiology and
      outcomes of invasive disease caused by typeable and nontypeable H. influenzae
      among Utah adults during 1998-2008. The overall incidence increased over the
      study period from 0.14/100,000 person-years in 1998 to 1.61/100,000 person-years
      in 2008. The average incidence in persons >65 years old was 2.74/100,000 person
      years, accounting for 51% of cases and 67% of deaths. The incidence was highest
      for nontypeable H. influenzae (0.23/100,000 person-years), followed by H.
      influenzae type f (0.14/100,000 person-years). The case-fatality rate was 22%.
      The incidence of invasive H. influenzae in Utah adults appears to be increasing.
      Invasive H. influenzae infection disproportionately affected the elderly and was
      associated with a high mortality rate.

PMID- 21888790
TI  - Central venous catheter-associated Nocardia bacteremia in cancer patients.
AB  - Central venous catheters, often needed by cancer patients, can be the source of
      Nocardia bacteremia. We evaluated the clinical characteristics and outcomes of 17
      cancer patients with Nocardia bacteremia. For 10 patients, the bacteremia was
      associated with the catheter; for the other 7, it was a disseminated infection.
      N. nova complex was the leading cause of bacteremia. Nocardia promoted heavy
      biofilm formation on the surface of central venous catheter segments tested in an
      in vitro biofilm model. Trimethoprim- and minocycline-based lock solutions had
      potent in vitro activity against biofilm growth. Patients with Nocardia central
      venous catheter-associated bloodstream infections responded well to catheter
      removal and antimicrobial drug therapy, whereas those with disseminated
      bacteremia had poor prognoses.

PMID- 21888791
TI  - Endemic scrub typhus-like illness, Chile.
AB  - We report a case of scrub typhus in a 54-year-old man who was bitten by several
      terrestrial leeches during a trip to Chiloe Island in southern Chile in 2006. A
      molecular sample, identified as related to Orientia tsutsugamushi based on the
      sequence of the16S rRNA gene, was obtained from a biopsy specimen of the eschar
      on the patient's leg. Serologic analysis showed immunoglobulin G conversion
      against O. tsutsugamushi whole cell antigen. This case and its associated
      molecular analyses suggest that an Orientia-like agent is present in the Western
      Hemisphere that can produce scrub typhus-like illness. The molecular analysis
      suggests that the infectious agent is closely related, although not identical, to
      members of the Orientia sp. from Asia.

PMID- 21888792
TI  - Geographic distribution of endemic fungal infections among older persons, United
      States.
AB  - To investigate the epidemiology and geographic distribution of histoplasmosis,
      coccidioidomycosis, and blastomycosis in older persons in the United States, we
      evaluated a random 5% sample of national Medicare data from 1999 through 2008. We
      calculated national, regional, and state-based incidence rates and determined 90
      day postdiagnosis mortality rates. We identified 776 cases (357 histoplasmosis,
      345 coccidioidomycosis, 74 blastomycosis). Patient mean age was 75.7 years; 55%
      were male. Histoplasmosis and blastomycosis incidence was highest in the Midwest
      (6.1 and 1.0 cases/100,000 person-years, respectively); coccidioidomycosis
      incidence rate was highest in the West (15.2). On the basis of available data,
      for 86 (11.1%) cases, there was no patient exposure to a traditional disease
      endemic area. Knowledge of areas where endemic mycosis incidence is increased may
      affect diagnostic or prevention measures for older adults at risk.

PMID- 21888793
TI  - Seroepidemiologic study of pandemic (H1N1) 2009 during outbreak in boarding
      school, England.
AB  - We conducted a seroepidemiologic study during an outbreak of pandemic (H1N1) 2009
      in a boarding school in England. Overall, 353 (17%) of students and staff
      completed a questionnaire and provided a serum sample. The attack rate was 40.5%
      and 34.1% for self-reported acute respiratory infection (ARI). Staff were less
      likely to be seropositive than students 13-15 years of age (staff 20-49 years,
      adjusted odds ratio [AOR] 0.30; >50 years AOR 0.20). Teachers were more likely to
      be seropositive than other staff (AOR 7.47, 95% confidence interval [CI] 2.31
      24.2). Of seropositive persons, 44.6% (95% CI 36.2%-53.3%) did not report ARI.
      Conversely, of 141 with ARI and 63 with influenza-like illness, 45.8% (95% CI
      37.0%-54.0%) and 30.2% (95% CI 19.2%-43.0%) had negative test results,
      respectively. A weak association was found between seropositivity and a
      prophylactic dose of antiviral agents (AOR 0.55, 95% CI 0.30-0.99); prophylactic
      antiviral agents lowered the odds of ARI by 50%.

PMID- 21888794
TI  - Leptospirosis as frequent cause of acute febrile illness in southern Sri Lanka.
AB  - To determine the proportion of fevers caused by leptospirosis, we obtained serum
      specimens and epidemiologic and clinical data from patients in Galle, Sri Lanka,
      March-October 2007. Immunoglobulin M ELISA was performed on paired serum
      specimens to diagnose acute (seroconversion or 4-fold titer rise) or past (titer
      without rise) leptospirosis and seroprevalence (acute). We compared
      (individually) the diagnostic yield of acute-phase specimens and clinical
      impression with paired specimens for acute leptospirosis. Of 889 patients with
      paired specimens, 120 had acute leptosoirosis and 241 had past leptospirosis. The
      sensitivity and specificity of acute-phase serum specimens were 17.5% (95%
      confidence interval [CI] 11.2%-25.5%) and 69.2% (95% CI 65.5%-72.7%),
      respectively, and of clinical impression 22.9% (95% CI 15.4%-32.0%) and 91.7%
      (95% CI 89.2%-93.8%), respectively. For identifying acute leptospirosis, clinical
      impression is insensitive, and immunoglobulin M results are more insensitive and
      costly. Rapid, pathogen-based tests for early diagnosis are needed.

PMID- 21888795
TI  - Inpatient capacity at children's hospitals during pandemic (H1N1) 2009 outbreak,
      United States.
AB  - Quantifying how close hospitals came to exhausting capacity during the outbreak
      of pandemic influenza A (H1N1) 2009 can help the health care system plan for more
      virulent pandemics. This ecologic analysis used emergency department (ED) and
      inpatient data from 34 US children's hospitals. For the 11-week pandemic (H1N1)
      2009 period during fall 2009, inpatient occupancy reached 95%, which was lower
      than the 101% occupancy during the 2008-09 seasonal influenza period. Fewer than
      1 additional admission per 10 inpatient beds would have caused hospitals to reach
      100% occupancy. Using parameters based on historical precedent, we built 5 models
      projecting inpatient occupancy, varying the ED visit numbers and admission rate
      for influenza-related ED visits. The 5 scenarios projected median occupancy as
      high as 132% of capacity. The pandemic did not exhaust inpatient bed capacity,
      but a more virulent pandemic has the potential to push children's hospitals past
      their maximum inpatient capacity.

PMID- 21888797
TI  - High rates of malaria among US military members born in malaria-endemic
      countries, 2002-2010.
AB  - To estimate malaria rates in association with birth country, we analyzed routine
      surveillance data for US military members. During 2002-2010, rates were 44*
      higher for those born in western Africa than for those born in the United States.
      Loss of natural immunity renders persons susceptible when visiting birth
      countries. Pretravel chemoprophylaxis should be emphasized.

PMID- 21888796
TI  - Mycobacterium chelonae-abscessus complex associated with sinopulmonary disease,
      Northeastern USA.
AB  - Members of the Mycobacterium chelonae-abscessus complex represent Mycobacterium
      species that cause invasive infections in immunocompetent and immunocompromised
      hosts. We report the detection of a new pathogen that had been misidentified as
      M. chelonae with an atypical antimicrobial drug susceptibility profile. The
      discovery prompted a multicenter investigation of 26 patients. Almost all
      patients were from the northeastern United States, and most had underlying sinus
      or pulmonary disease. Infected patients had clinical features similar to those
      with M. abscessus infections. Taxonomically, the new pathogen shared molecular
      identity with members of the M. chelonae-abscessus complex. Multilocus DNA target
      sequencing, DNA-DNA hybridization, and deep multilocus sequencing (43 full-length
      genes) support a new taxon for these microorganisms. Because most isolates
      originated in Pennsylvania, we propose the name M. franklinii sp. nov. This
      investigation underscores the need for accurate identification of Mycobacterium
      spp. to detect new pathogens implicated in human disease.

PMID- 21888798
TI  - Differential risk for Lyme disease along hiking trail, Germany.
AB  - To estimate relative risk for exposure to ticks infected with Lyme disease
      causing spirochetes in different land-use types along a trail in Germany, we
      compared tick density and spirochete prevalence on ruminant pasture with that on
      meadow and fallow land. Risk was significantly lower on pasture than on meadow
      and fallow land.

PMID- 21888799
TI  - Bartonella quintana infections in captive monkeys, China.
AB  - Bartonella quintana has been considered to be specifically adapted to humans. Our
      isolation of the organism from 2 of 36 captive rhesus macaques in China and
      finding antibodies against B. quintana in 12 of 33 indicates that the reservoir
      hosts of B. quintana may include primates other than humans.

PMID- 21888800
TI  - Canine serology as adjunct to human Lyme disease surveillance.
AB  - To better define areas of human Lyme disease risk, we compared US surveillance
      data with published data on the seroprevalence of Borrelia burgdorferi antibodies
      among domestic dogs. Canine seroprevalence >5% was a sensitive but nonspecific
      marker of human risk, whereas seroprevalence <1% was associated with minimal risk
      for human infection.

PMID- 21888801
TI  - Predominance of Cronobacter sakazakii sequence type 4 in neonatal infections.
AB  - A 7-loci (3,036 nt) multilocus sequence typing scheme was applied to 41 clinical
      isolates of Cronobacter sakazakii. Half (20/41) of the C. sakazakii strains were
      sequence type (ST) 4, and 9/12 meningitis isolates were ST4. C. sakazakii ST4
      appears to be a highly stable clone with a high propensity for neonatal
      meningitis.

PMID- 21888802
TI  - Wild rodents and novel human pathogen candidatus Neoehrlichia mikurensis,
      Southern Sweden.
AB  - We examined small mammals as hosts for Anaplasmataceae in southern Sweden. Of 771
      rodents, 68 (8.8%) were infected by Candidatus Neoehrlichia mikurensis, but no
      other Anaplasmataceae were found. Candidatus N. mikurensis has recently been
      found in human patients in Germany, Switzerland, and Sweden, which suggests that
      this could be an emerging pathogen in Europe.

PMID- 21888803
TI  - Q fever among culling workers, the Netherlands, 2009-2010.
AB  - In 2009, dairy goat farms in the Netherlands were implicated in >2,300 cases of Q
      fever; in response, 51,820 small ruminants were culled. Among 517 culling
      workers, despite use of personal protective equipment, 17.5% seroconverted for
      antibodies to Coxiella burnetii. Vaccination of culling workers could be
      considered.

PMID- 21888804
TI  - Syndromic surveillance during pandemic (H1N1) 2009 outbreak, New York, New York,
      USA.
AB  - We compared emergency department and ambulatory care syndromic surveillance
      systems during the pandemic (H1N1) 2009 outbreak in New York City. Emergency
      departments likely experienced increases in influenza-like-illness significantly
      earlier than ambulatory care facilities because more patients sought care at
      emergency departments, differences in case definitions existed, or a combination
      thereof.

PMID- 21888805
TI  - Tubulinosema sp. microsporidian myositis in immunosuppressed patient.
AB  - The Phylum Microsporidia comprises >1,200 species, only 15 of which are known to
      infect humans, including the genera Trachipleistophora, Pleistophora, and
      Brachiola. We report an infection by Tubulinosema sp. in an immunosuppressed
      patient.

PMID- 21888806
TI  - Listeriosis, Taiwan, 1996-2008.
AB  - During 1996-2008, a total of 48 patients with listeriosis were identified at a
      Taiwan hospital. Average annual incidence increased from 0.029 to 0.118 cases per
      1,000 admissions before and after January 2005. Serotype 1/2b predominated;
      serotype 4b emerged since 2004. Food monitoring and disease surveillance systems
      could help control listeriosis in Taiwan.

PMID- 21888807
TI  - Tattoo-associated Mycobacterium haemophilum skin infection in immunocompetent
      adult, 2009.
AB  - After a laboratory-confirmed case of Mycobacterium haemophilum skin infection in
      a recently tattooed immunocompetent adult was reported, we investigated to
      identify the infection source and additional cases. We found 1 laboratory
      confirmed and 1 suspected case among immunocompetent adults who had been tattooed
      at the same parlor.

PMID- 21888808
TI  - Pandemic (H1N1) 2009 transmission during presymptomatic phase, Japan.
AB  - During an epidemiologic investigation of pandemic influenza (H1N1) 2009 virus
      infection in May 2009 in Osaka, Japan, we found 3 clusters in which virus
      transmission occurred during the presymptomatic phase. This finding has public
      health implications because it indicates that viral transmission in communities
      cannot be prevented solely by isolating symptomatic case-patients.

PMID- 21888809
TI  - Increased extent of and risk factors for pandemic (H1N1) 2009 and seasonal
      influenza among children, Israel.
AB  - During the pandemic (H1N1) 2009 outbreak in Israel, incidence rates among
      children were 2* higher than that of the previous 4 influenza seasons;
      hospitalization rates were 5* higher. Children hospitalized for pandemic (H1N1)
      2009 were older and had more underlying chronic diseases than those hospitalized
      for seasonal influenza.

PMID- 21888810
TI  - Hospitalized patients with pandemic (H1N1) 2009, Kenya.
AB  - To describe the epidemiology and clinical course of patients hospitalized with
      pandemic (H1N1) 2009 in Kenya, we reviewed medical records of 49 such patients
      hospitalized during July-November 2009. The median age (7 years) was lower than
      that in industrialized countries. More patients had HIV than the general Kenyan
      population.

PMID- 21888811
TI  - Ciprofloxacin-resistant Shigella sonnei among men who have sex with men, Canada,
      2010.
AB  - In 2010, we observed isolates with matching pulsed-field gel electrophoresis
      patterns from 13 cases of ciprofloxacin-resistant Shigella sonnei in Montreal. We
      report on the emergence of this resistance type and a study of resistance
      mechanisms. The investigation suggested local transmission among men who have sex
      with men associated with sex venues.

PMID- 21888812
TI  - Multidrug-resistant Acinetobacter baumannii in veterinary clinics, Germany.
AB  - An increase in prevalence of multidrug-resistant Acinetobacter spp. in
      hospitalized animals was observed at the Justus-Liebig-University (Germany).
      Genotypic analysis of 56 isolates during 2000-2008 showed 3 clusters that
      corresponded to European clones I-III. Results indicate spread of genotypically
      related strains within and among veterinary clinics in Germany.

PMID- 21888813
TI  - Escherichia coli O104:H4 from 2011 European outbreak and strain from South Korea.

PMID- 21888814
TI  - Respiratory illness in households of school-dismissed students during pandemic
      (H1N1) 2009.

PMID- 21888815
TI  - Pandemic (H1N1) 2009 virus in swine herds, People's Republic of China.

PMID- 21888817
TI  - Carriage of meningococci by university students, United Kingdom.

PMID- 21888816
TI  - Pulmonary disease associated with nontuberculous mycobacteria, Oregon, USA.

PMID- 21888818
TI  - Pandemic (H1N1) 2009 in neonates, Japan.

PMID- 21888819
TI  - Social network as outbreak investigation tool.

PMID- 21888820
TI  - Susceptibility of health care students to measles, Paris, France.

PMID- 21888821
TI  - Toxigenic Corynebacterium ulcerans in woman and cat.

PMID- 21888822
TI  - Isoniazid-resistant tuberculosis, taiwan, 2000-2010.

PMID- 21888823
TI  - Novel mycobacterium species in seahorses with tail rot.

PMID- 21888824
TI  - Mycoplasma leachii sp. nov. in calves, China.

PMID- 21888825
TI  - Bartonella clarridgeiae in fleas, Tahiti, French Polynesia.

PMID- 21888826
TI  - Bocavirus in children with respiratory tract infections.

PMID- 21888827
TI  - Highly virulent Escherichia coli O26, Scotland.

PMID- 21888828
TI  - Perinatal transmission of yellow fever, Brazil, 2009.

PMID- 21888829
TI  - Pathogenic Leptospira spp. in wild rodents, Canary Islands, Spain.

PMID- 21888830
TI  - Highly pathogenic porcine reproductive and respiratory syndrome virus, Asia.

PMID- 21888831
TI  - Unfolded protein response suppresses cisplatin-induced apoptosis via autophagy
      regulation in human hepatocellular carcinoma cells.
AB  - It has been shown that drug resistance is extremely common in hepatocellular
      carcinoma (HCC) and is one of the major problems in HCC chemotherapy. However,
      the detailed mechanisms remain largely unknown. We have previously shown that
      endoplasmic reticulum (ER) stress is involved in the tumorigenesis of HCC. Here,
      we demonstrated that the unfolded protein response (UPR) inhibits cisplatin
      induced HCC cell apoptosis. In HCC cells, cisplatin treatment triggers the UPR,
      which subsequently inhibits cisplatin-induced apoptosis. Importantly, mild ER
      stress precondition suppresses the sensitivity of HCC cells to cisplatin-induced
      apoptosis through autophagy regulation. Furthermore, heat-shock protein 27
      (Hsp27) is involved in the cytoprotective role of the UPR in cisplatin-induced
      apoptosis. We also demonstrated that Hsp27 inhibits cisplatin- induced HCC cell
      death through autophagy activation. Taken together, our results indicate that the
      UPR inhibits cisplatin-induced apoptosis in HCC cells, at least in part, by Hsp27
      mediated autophagy activation.

PMID- 21888832
TI  - Glucose and its metabolites have distinct effects on the calcium-induced
      mitochondrial permeability transition.
AB  - Mitochondrial production of reactive oxygen species (ROS) due to up-regulated
      glucose oxidation is thought to play a crucial, unifying role in the pathogenesis
      of chronic complications associated with diabetes mellitus. Mitochondrial
      permeability transition (MPT) is an interesting phenomenon involved in calcium
      signalling and cell death. We investigated the effects of glucose and several of
      its metabolites on calcium-induced MPT (measured as mitochondrial swelling) in
      isolated rat liver mitochondria. The presence of glucose, glucose 1-phosphate
      (both at 30 mM) or methylglyoxal (6 mM) significantly slowed calcium-induced
      mitochondrial swelling. Thirty mM glucose also resulted in a significant delay of
      MPT onset. In contrast, 30 mM fructose 6-phosphate accelerated swelling, whereas
      glucose 6-phosphate did not influence the MPT. The calcium binding potentials of
      the three hexose phosphates were tested and found similar. In vitro hydrogen
      peroxide production by mitochondria respiring on succinate in the presence of
      rotenone was independent of mitochondrial membrane potential and increased
      transiently during calcium-induced MPT. Inhibition of MPT with cyclosporine A
      resulted in decreased mitochondrial ROS production in response to calcium. In
      contrast, inhibition of MPT by methylglyoxal was accompanied by increased ROS
      production in response to calcium. In conclusion, we confirm that methylglyoxal
      is a potent inhibitor of MPT. In addition, high levels of glucose, glucose 1
      phosphate and fructose 6-phosphate can also affect MPT. Methylglyoxal
      simultaneously inhibits MPT and increases mitochondrial ROS production in
      response to calcium. Our findings provide a novel context for the role of MPT in
      glucose sensing and the cellular toxicity caused by methylglyoxal.

PMID- 21888833
TI  - Changes in expression of some apoptotic markers in different types of human
      endometrium.
AB  - The maintenance of tissue homeostasis and highly balanced counteraction of
      cellular proliferation and apoptosis are essential for tissue integrity. In our
      study, we evaluated the expression of apoptosis- regulating proteins Bcl-2, Bax
      and PARP, and executive apoptotic enzyme caspase-3 in normal, atrophic,
      hyperplastic and cancerous endometrium. Endometrial samples were obtained from
      patients who underwent curettage, hysteroresection or hysterectomy. The protein
      levels were quantified by immunoblotting. We observed a higher level of important
      apoptotic enzyme pro-caspase-3 and its active form in hyperplastic and cancerous
      endometrium, when compared to normal endometrium. The value of Bcl-2/Bax ratio,
      which reflects cellular resistance to apoptosis, was determined as > 1 for
      cancerous, normal, and atrophic endometrium. Thus, the effort to eliminate pre
      neoplastic and neoplastic cells by apoptosis indicated by high pro-caspase-3 and
      caspase-3 levels seems to be overcome by a greater proliferative adjustment
      suggested by higher Bcl-2/Bax ratios in the samples examined. The PARP levels did
      not vary significantly among the groups. The levels of all examined proteins were
      significantly lower in atrophic endometrium. Our results suggest that pre
      neoplastic and neoplastic states of human endometrium are not influenced simply
      by changes in apoptosis, but may also be affected by cellular proliferation. A
      high Bcl-2/Bax ratio as observed in cancerous endometrium can point to
      deregulation of apoptotic programmes. Thus, the onset and progression of
      endometrial malignancy could be linked to increased cellular proliferation with
      defects in apoptotic control.

PMID- 21888834
TI  - The influence of electroporation on in vitro photodynamic therapy of human breast
      carcinoma cells.
AB  - Phototoxicity of drugs used in cancer photodynamic therapy could be augmented by
      increased accumulation of a photosensitizer in target cells. The intracellular
      delivery mode that enhances drug transportation could facilitate therapy by
      reducing the exposure time. Doses of the administered drug and related side
      effects could be lowered, whilst maintaining the same therapeutic efficiency.
      Electroporation supports transport of many drugs by creating electric field
      induced transient nanopores in the plasma membrane. In this study, the
      electroporation- assisted transport of a photosensitizer was tested in vitro in
      human breast carcinoma cell lines: wild-type (MCF-7/WT) and doxorubicin-resistant
      (MCF-7/DOX). The efficacy of photodynamic therapy alone and in combination with
      electroporation was evaluated by cell viability with MTT test, using a
      haematoporphyrin derivative as a model. The data presented show up to 10-fold
      greater efficacy of the combined method, with very significantly reduced drug
      exposure times.

PMID- 21888835
TI  - Isolation and characterization of synovial mesenchymal stem cells.
AB  - Synovial membrane and synovial fluid represent a good source of mesenchymal stem
      cells. They have been regarded as a promising therapeutic tool for
      musculoskeletal regeneration. Synovium-derived mesenchymal stem cells have higher
      expression of CD44 and better chondrogenic potential in vitro than mesenchymal
      stem cells from other tissues. In this study we compared mesenchymal stem cells
      from synovium and synovial fluid on the base of morphological, immunophenotype
      and differentiation features. A heterogeneous population of cells with different
      morphology was obtained after isolation and 4-day cultivation. The mesenchymal
      stem cell immunophenotype was confirmed by positive expression of CD105, CD90,
      and CD44 by flow cytometry and cells were negative for CD45. CD105+ cells were
      selected by immunomagnetic separation after 2-4 weeks of cultivation. The
      percentage of CD105+ cells in the mesenchymal stem cell population from synovia
      was between 40-50 % before immunomagnetic separation and increased to 95 %
      following the immunomagnetic separation. Von Kossa, Alcian blue and Oil Red O
      staining was used to assess the differentiation potential of synovial mesenchymal
      stem cells. Long-term cultivation did not affect the morphology and
      immunophenotype of synovial mesenchymal stem cells. Our results confirmed that
      immunomagnetic separation based on CD 105 antigen is a suitable method to enrich
      the subpopulation of CD105+ synovial mesenchymal stem cells.

PMID- 21888836
TI  - Comparative analysis of the nuclear presence of adhesion/growth-regulatory
      galectins and reactivity in the nuclei of interphasic and mitotic cells.
AB  - Nuclear galectins participate in splicing of pre-mRNA. In this study we detected
      galectins-1, -2, -3 and -7 and their glycoligands in three types of cells:
      fibroblasts, cancer epithelial cells and melanoma cells. The results demonstrated
      that the nuclear expression of distinct types of galectins and their ligands in
      interphasic nuclei is dependent on the cell type. The extensive binding of
      labelled galectins-1 and -2 to mitotic cells (around chromosomes, in mitotic
      spindle and in bridge connecting both daughter cells) suggests their role during
      the cell division.

PMID- 21888838
TI  - Clavicle fractures--is there a standard treatment?
AB  - Clavicle fractures, especially of the mid third, are an injury commonly seen in
      clinical practice, therefore, there is constant earnest discussion of the optimal
      approach to therapy. Until recently clavicle fractures were solely the domain of
      non surgical management. Even displaced fractures have been successfully managed
      without surgery. However, complications have been reported after non surgical
      treatment, the most frequent being post-traumatic shortening of the clavicle with
      varying functional consequences for the shoulder joint and range of arm motion as
      well as pseudarthrosis, especially after more severely displaced fractures.
      Recent studies have now shown that outcomes after non surgical management of
      displaced fractures or shortening of the clavicle are worse than had been
      previously assumed. Surgical techniques for the stable fixation of clavicle
      fractures have been improved and a wider selection of implants for osteosynthesis
      of these fractures has become available. Although there is widespread consensus
      that undisplaced or minimally displaced clavicle fractures respond well to non
      surgical management, optimal treatment of displaced fractures or severe
      shortening is under scrutiny with regard to both the basic choice between non
      surgical or surgical management and implant selection. According to current
      research findings, surgical management of displaced clavicle fractures has
      advantages and appears to be superior to non surgical management. Intramedullary
      nailing has proven suitable for simple straight fractures, and plate fixation for
      multifragmentary fractures.

PMID- 21888837
TI  - Clopidogrel and modified-release dipyridamole for the prevention of occlusive
      vascular events (review of Technology Appraisal No. 90): a systematic review and
      economic analysis.
AB  - BACKGROUND: Occlusive vascular events such as myocardial infarction (MI),
      ischaemic stroke and transient ischaemic attack (TIA) are the result of a
      reduction in blood flow associated with an artery becoming narrow or blocked
      through atherosclerosis and atherothrombosis. Peripheral arterial disease is the
      result of narrowing of the arteries that supply blood to the muscles and other
      tissues, usually in the lower extremities. The primary objective in the treatment
      of all patients with a history of occlusive vascular events and peripheral
      arterial disease is to prevent the occurrence of new occlusive vascular events.
      OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of
      clopidogrel and modified-release dipyridamole (MRD) alone or with aspirin (ASA)
      compared with ASA (and each other where appropriate) in the prevention of
      occlusive vascular events in patients with a history of MI, ischaemic stroke/TIA
      or established peripheral arterial disease. To consider the clinical
      effectiveness and cost-effectiveness of clopidogrel in patients with
      multivascular disease. This review is an update of the evidence base for the
      National Institute for Health and Clinical Excellence (NICE) guidance Technology
      Appraisal No. 90 (TA90) entitled Clopidogrel and modified-release dipyridamole
      for the prevention of occlusive vascular events (2005). DATA SOURCES: Four
      electronic databases (EMBASE, MEDLINE, Web of Science and The Cochrane Library)
      were searched for randomised controlled trials (RCTs) and economic evaluations.
      Submissions to NICE by the manufacturers of the interventions were also
      considered. REVIEW METHODS: A systematic review of clinical effectiveness and
      cost-effectiveness was conducted. To manage heterogeneity between trials,
      indirect analysis (using a mixed-treatment methodology) was performed on selected
      clinical outcomes. A new economic model was developed to assess incremental costs
      per life-year gained [quality-adjusted life-years (QALYs)]. RESULTS: For evidence
      of clinical effectiveness, four RCTs were identified: CAPRIE (Clopidogrel versus
      Aspirin in Patients at Risk of Ischaemic Events), ESPRIT (European/Australasian
      Stroke Prevention in Reversible Ischaemia Trial), PRoFESS (Prevention Regimen For
      Effectively avoiding Second Strokes) and ESPS-2 (Second European Stroke
      Prevention Study). In CAPRIE (patients with MI, ischaemic stroke or peripheral
      arterial disease), statistically significant outcomes in favour of clopidogrel
      were noted for the primary outcome (first occurrence of ischaemic stroke, MI or
      vascular death) compared with ASA [relative risk reduction 8.7%; 95% confidence
      interval (CI) 0.3% to 16.5%; p = 0.043]. In ESPRIT (patients with ischaemic
      stroke/TIA) for the primary outcome (first occurrence of death from all vascular
      causes, non-fatal stroke, non-fatal MI or major bleeding complication), the risk
      of event occurrence was statistically significantly lower in the MRD + ASA arm
      than in the ASA arm [hazard ratio (HR) 0.80; 95% CI 0.66 to 0.98], with no
      statistically significant difference in bleeding events between the two arms. In
      PRoFESS (patients with ischaemic stroke) the rate of recurrent stroke of any type
      (primary outcome) was similar in the MRD + ASA and clopidogrel groups, and the
      null hypothesis (that MRD + ASA was inferior to clopidogrel) could not be
      rejected. In ESPS-2 (patients with ischaemic stroke/TIA), on the primary outcome
      of stroke, statistically significant differences in favour of MRD + ASA were
      observed compared with ASA and MRD alone (relative risk 0.76; 95% CI 0.63 to
      0.93). The outcomes addressed in the mixed-treatment comparisons (limited by the
      available data) for the ischaemic stroke/TIA population confirmed the results of
      the direct comparisons. The 11 economic evaluations included in the review of
      cost-effectiveness indicated that for patients with previous peripheral arterial
      disease, ischaemic stroke or MI, clopidogrel is cost-effective compared with ASA,
      and for patients with previous ischaemic stroke/TIA, treatment with MRD + ASA is
      cost-effective compared with any other treatment in patients in the secondary
      prevention of occlusive vascular events. The relevance of the review was limited
      as the economic evaluations were not based on the most current clinical data.
      Cost-effectiveness results generated from the Assessment Group's de novo economic
      model suggested that the most cost-effective approach for patients with ischaemic
      stroke/TIA is clopidogrel followed by MRD + ASA then ASA. For patients with MI,
      the most cost-effective approach is ASA followed by clopidogrel. For patients
      with established peripheral arterial disease, the most cost-effective approach is
      clopidogrel followed by ASA. For patients with multivascular disease, clopidogrel
      followed by ASA is the most cost-effective approach. Incremental cost
      effectiveness ratios (ICERs) were also calculated for patients who are intolerant
      to ASA. Assuming that the branded price for clopidogrel is used and TA90 guidance
      is not applied, all of the ICERs range between L2189 and L13,558 per QALY gained.
      Probabilistic sensitivity analyses were fully consistent with these findings.
      CONCLUSIONS: The evidence suggests that the most cost-effective treatment for
      patients with ischaemic stroke/TIA is clopidogrel followed by MRD + ASA followed
      by ASA; for patients with MI, ASA followed by clopidogrel; and for patients with
      established peripheral arterial disease or multivascular disease, clopidogrel
      followed by ASA. FUNDING: The National Institute for Health Research Health
      Technology Assessment programme.

PMID- 21888839
TI  - Fractures of the scapula.
AB  - The scapula connects the arm with the chest wall and is therefore of great
      importance for a free range of shoulder of motion. For a long-term scapular
      fractures had been treated predominantly conservative. However, clinical studies
      of the past decades revealed that some fracture patterns deserve operative
      treatment to prevent unfavorable functional outcome and chronic state of pain.
      Scapular fractures are predominantly acquired during high-energy trauma and these
      patients' presents with a mean of 3.9 associated injuries in the emergency
      department. Injuries to the head, chest and ipsilateral upper extremity are most
      common. As some of these injuries are possibly life threatening they are treated
      first. Scapular fractures are only very seldom surgical emergencies. Therefore
      they are treated during the phase of reconvalescence in polytraumatized patients.
      Decision-making should be based on a thoroughgoing diagnostics, including
      conventional x-rays and a CT-scan, epically in cases of glenoid neck or cavity
      fractures. All fracture patterns should be identified to there full extend and
      put into the context of the scapular suspensory complex. The OTA lately presented
      a new and comprehensive system for classification of the scapular fractures. It
      is divided in two levels. Level one for the general orthopedic or trauma surgeon
      and Level two for the advanced upper Extremity or Shoulder surgeon. This
      classification scheme allows an easy access to understanding of the severity and
      prognostics of scapular fractures. As a general guideline surgery is indicated if
      a double disruption of the Scapula suspensory system, a relevant malposition or
      dysintegrity of the glenoid (articular surface) or a displacement of the lateral
      column is present.

PMID- 21888840
TI  - [Current role of methylprednisolone in the treatment of acute spinal cord
      injury].
AB  - High doses of methylprednisolone (MPSS) came into use as part of a therapeutic
      protocol for acute spinal cord injuries following the published results from the
      NASCIS II study in 1992; they soon became a standard of care around the world.
      However, the results of this study have been critically reviewed and questioned
      by many authors since the beginning. The major argument is based on the fact that
      its effectiveness in reducing post-injury neurological damage has not been
      conclusively proved; in addition, there has been increasing evidence of serious
      side effects of steroids administered at high doses. In the Czech Republic, as
      part of pre-hospital care, MPSS according to the NASCIS II (or NASCIS III)
      protocol is used in all regional centres of emergency medical service. In the
      Czech spinal surgery centres involved in treating acute spinal cord injuries,
      there are 19 of them, attitudes towards the use of MPSS vary. In 16% of the
      centres a certainty of its beneficial effect is still maintained, faith in its
      effect together with fear of a "non-lege artis" procedure is the reason for MSPP
      use in 21%, and the fear of sanctions only leads to its use in 63% of the
      centres. There is no standard practice in application of the NASCIS II and NASCIS
      III protocols and no standard exclusion criteria exist. The two protocols are
      used equally, and one institution has its own modification. The recommended MPSS
      dose is administered with no exception in 63% of the centres; dose adjustment is
      employed according to the form of spinal cord lesion in 11%, the level of spinal
      cord injury in 5%, associated diseases in 16% and patient age in 11% of the
      spinal surgery centres. After the results of studies on MPSS administration in
      acute spinal cord injury have been analysed, many medical societies have changed
      their recommendations. In view of later relevant publications it is no longer
      possible to regard MPSS administration as a standard of cure for acute spinal
      cord injury. Current evidence suggests that MPSS administration in a 24-hour
      regimen after an initial dose given within 8 hours of injury is the therapeutic
      procedure that needs individual consideration in each patient according to their
      state of health and potential complications. MPSS administration at an interval
      longer than 8 hours after injury and for more than 24 hours is not justified, nor
      is it justified to use a high MPSS dose at the place of injury by an emergency
      ambulance crew. Key words: corticosteroids, methylprednisolone, spinal cord
      trauma, neurological damage.

PMID- 21888841
TI  - [Comparison of functional outcomes in angle-stable osteosynthesis of comminuted
      fractures of the proximal humerus with those in percutaneous Kirschner-wire
      fixation. A prospective study of mid-term results].
AB  - PURPOSE OF THE STUDY: To evaluate the mid-term results in a group of patients
      with displaced comminuted (three- and four-fragment) fractures of the proximal
      humerus treated by angle-stable plate osteosynthesis and compare them with the
      results in the patients in whom the method of percutaneous Kirschner-wire (K
      wire) fixation was used. MATERIAL AND METHODS: The group treated with angle
      stable implants (ASI group) consisted of 55 patients, 13 men and 42 women. A
      Targon Ph nail was used in 32 and a Philos plate in 23 patients. These patients
      were compared with a group of nine patients, one man and eight women, treated by
      percutaneous K-wire fixation (K-wire group). At a follow-up of 12 months at
      least, final Constant (CS) and DASH scores were assessed. The CS was related to
      the values for the unaffected limb, and an individual relative CS was calculated
      and expressed in percent. The mean follow-up was 30 (range, 13-55) months in the
      ASI group and 58 (range, 39-76) months in the K-wire group. The following seven
      characteristics were evaluated : fracture type, surgical technique, dominance of
      the affected limb, patient age, injury-surgery interval, and individual relative
      CS and DASH scores. The results were statistically analysed with a 5% level of
      statistical significance set for all tests. RESULTS: The average age in the ASI
      group was 62.1 years, with 64.7 (range, 29-95) years for women and 35.5 (range,
      26-76) years for men. In the K-wire group the average age was 66.1 (range, 53-84)
      years. The functional outcomes in four-fragment fractures were significantly
      worse than in three-fragment fractures (mean relative CS and DASH scores of 56
      and 21 versus 72 and 32). The K-wire group showed a significantly worse
      functional outcomes than the ASI group in both the mean relative CS score
      (p<0.001) and the mean DASH score (p=0.003). No significant relationship was
      found in any other pair of variables. The patient's age had no effect on
      functional outcome, as assessed by CS (p=0.412) and DASH (p=0.076) and the injury
      surgery interval had no influence, either (CS, p=0.220; DASH, p=0.118). There was
      no relation between the patient's age and choice of the surgical method
      (p=0.467), between the patient's age and a fracture type (p=0.356) and between
      the patient's age and injury to either a dominant or a non-dominant limb
      (p=0.659). Dominance or non-dominance of the affected limb had no effect on CS or
      DASH scores (p=0.662 and p=0.302, respectively) or on a type of fracture
      (p=0.183). DISCUSSION: Several surgical techniques used for the treatment of
      proximal humerus fractures suggest the absence of consensus in therapy. Novel
      angle-stable implants show better biochemical properties and meet criteria
      required in minimally invasive techniques. Some authors prefer intramedullary
      nailing for three-fragment fractures and the use of an angle-stable plate for
      four-fragment fractures. These indication criteria were also confirmed by the
      results of our study. CONCLUSIONS: The analysis of functional outcomes showed
      that the therapeutic effect of K-wire transfixation was significantly worse than
      the effect of the angle-stable plate technique, and therefore the authors stopped
      using this method. At present intramedullary nailing is indicated in two- and
      three-fragment fractures and in some less displaced four-fragment fractures. An
      angle-stable plate is used in severely displaced four-fragment fractures. If the
      head is broken or dislocated, older patients are primarily indicated for
      hemiarthroplasty and younger ones for humeral head reconstruction.

PMID- 21888843
TI  - [Mathematical simulation of biomechanical background of osteophyte formation in
      cervical vertebra].
AB  - PURPOSE OF THE STUDY: The aim of this study was to simulate different types of
      cervical vertebra loading and to find out whether mechanical stress would
      concentrate in regions known in clinical practice as predilection sites for
      osteophyte formation. The objective was to develop a theoretical model that would
      elucidate clinical observations concerning the predilection site of bone
      remodelling in view of the physiological changes inside the cervical vertebral
      body. MATERIAL AND METHODS: A real 3D-geometry of the fourth cervical vertebra
      had been made by the commercially available system ATOS II. This is a high
      resolution measuring system using principles of optical triangulation. This
      flexible optical measuring machine projects fringe patterns on the surface of a
      selected object and the pattern is observed with two cameras. 3D coordinates for
      each camera pixel were calculated with high precision and a polygon mesh of the
      object's surface was further generated. In the next step an ANSYS programme was
      used to calculate strains and stresses in each finite element of the virtual
      vertebra. The applied forces used in the experiment corresponded in both
      magnitude and direction to physiological stress. Mechanical loading in neutral
      position was characterized by a distribution of 80% mechanical stress to the
      vertebral body and 10% to each of the zygoapophyseal joints. Hyperlordotic
      loading was simulated by 60% force transfer to the vertebral body end-plate and
      20% to each of the small joint while kyphotic loading involved a 90% load on the
      vertebral body endplate and 5% on each facet. RESULTS: Mechanical stress
      distribution calculated in a neutral position of the model correlated well with
      bone mineral distribution of a healthy vertebra, and verified the model itself.
      The virtual mechanical loading of a vertebra in kyphotic position concentrated
      deformation stress into the uncinate processes and the dorsal apophyseal rim of
      the vertebral body. The simulation of mechanical loading in hyperlordosis, on the
      other hand, shifted the region of maximum deformation into the articulation
      process of the Z-joint. All locations are known as areas of osteophyte formation
      in degenerated cervical vertebrae. DISCUSSION AND CONCLUSIONS: The theoretical
      model developed during this study corresponded well with human spine behaviour in
      terms of predilection sites for osteodegenerative changes, as observed in
      clinical practice. A mathematical simulation of mechanical stress distribution in
      pre-operative planning may lead to the optimisation of post-operative anatomical
      relationship between adjacent vertebrae. Such improvement in our surgical
      practice may further reduce the incidence of degenerative changes in adjacent
      motion segments of the cervical spine and possibly also lead to better subjective
      and clinical results after cervical spine reconstruction.

PMID- 21888842
TI  - [Surgical treatment for proximal humerus fracture].
AB  - PURPOSE OF THE STUDY: The aim of the study was to compare the medical aspects of
      alternative surgical methods for treatment of proximal humerus fractures in
      specific indications (two- and three- fragment fractures). MATERIAL AND METHODS:
      A prospective randomised study on surgical treatment of two- and three-fragment
      fractures of the proximal humerus was carried out at the Department of Surgery,
      University Hospital in Hradec Kralove, from January 2006 till January 2010. The
      study comprised patients with proximal humerus fractures indicated for surgical
      treatment. Study inclusion criteria were as follows: informed consent, AO
      fracture types A2, A3, B1 or C1, age between 18 and 80 years, and patient
      compliance. Exclusion criteria included open fracture, associated injury (AIS .
      2), open growth plates, or such state of the patient's health that would limit
      the extent of surgery. Two groups were compared. One included patients treated by
      the Zifko method of minimally invasive osteosynthesis with intramedullary K-wire
      insertion (MIO group) and the other (ORIF group) consisted of patients undergoing
      open reduction with angle-stable osteosynthesis using a Philos plate (Synthes,
      Switzerland). The patients were randomised to the groups by a computer programme
      which facilitates the maintenance of homogeneity of the groups compared. The
      procedure in each patient was based on the sealed-envelope method. RESULTS: The
      ORIF group comprised 28 patients. It took them an average of 27.2 weeks (9-72) to
      regain normal upper limb function. The final CM score was 86.6% (64-100%) as
      compared with the healthy limb. Excellent and good results were achieved in 89%
      of the patients; complications were recorded in 39% of them. The MIO group
      included 27 patients. The fractures healed in all of them. Normal upper limb
      function was regained at an average of 21.4 weeks (13-36). The final CM score was
      87.5% (52-100%) in comparison with the healthy limb. Excellent and good results
      were achieved in 89% and complications developed in 33% of the patients.
      CONCLUSIONS: The statistical evaluation of the results, using the unpaired t
      test, did not show any significant differences either in functional outcomes or
      the number of complications between the two groups. The only significant
      difference was found in operative times (117 min and 72 min in ORIF and MIO
      groups, respectively). The difference in time needed to regain limb function (27
      and 21 weeks) was at a marginal level of statistical significance. With both
      methods 89% of excellent and good results were achieved, and a similar number of
      patients had complications (11 and 9).

PMID- 21888844
TI  - [A comparative analysis of Socon CS and Socon pedicle screws in view of their use
      for treatment of osteoporotic fractures of the thoracolumbal spine--a
      biomechanical study].
AB  - PURPOSE OF THE STUDY: To compare the anchorage strength of Socon CS cannulated
      pedicle screws (B. Braun, Aesculap) with that of Socon screws in human cadaver
      vertebrae, using pull-out strength testing. MATERIAL: Twelve samples involving
      T12 to L3 vertebrae were prepared and a total of 20 pedicle screws, 10 Socon CS
      and 10 Socon screws, were inserted in them. All screws were 55 mm in length and 6
      mm in diameter. After placement, Socon CS pedicle screws were augmented with bone
      cement (Cimplant cement application kit, B. Braun, Aesculap). METHODS: Both Socon
      CS and Socon screws were subjected to monotonous loading in the testing device
      ZWICK Z 020-TND with tensile stress applied in the screw axis. We evaluated the
      magnitude of strength resulting in screw loosening and the relationship between
      this strength and bone density of the sample. RESULTS: Bone density of measured
      samples corresponded either to osteopenia, i.e. T-score range of -1 to -2.5 SD
      (standard deviation) or osteoporosis, i.e. T-score -2.5 SD. The average bone
      density of all samples corresponded to a T-score of -3.1 SD. Bone-screw linkage
      was found to be associated with both bone-cement and screw-cement interface. Pull
      out strength was significantly higher for the Socon CS than the Socon screws (t
      test, p<0.0005). In the Socon screws, the linear correlation between pull-out
      strength and bone density was significant at a 5% level of statistical
      significance (p=0.008) while, in the Socon CS screws, it was not significant
      (p=0.065). DISCUSSION: The poor quality of osteoporotic bone is responsible for a
      higher frequency of implant failure due to loosening, particularly when implants
      developed for healthy bone are used. In this biomechanical study, we tested one
      of the possibilities of how to reduce the risk of implant failure by pedicle
      screw augmentation with bone cement. CONCLUSIONS: The results of this study
      confirm the hypothesis that the anchorage of Socon CS cannulated pedicle screws
      with bone cement augmentation is disrupted by significantly higher pull-out
      strength than that of Socon screws, when subjected to monotonous loading.
      However, more clinical studies are needed to evaluate clinical outcomes.

PMID- 21888845
TI  - [Injection of anaesthetic-corticosteroid to relieve sacroiliac joint pain after
      lumbar stabilisation].
AB  - PURPOSE OF THE STUDY: Both the range of motion and load transfer of the
      sacroiliac (SI) joint improve considerably after lumbar spine surgery. When,
      following surgery, SI joint pain develops in spite of appropriate physical
      therapy, injection of an anaesthetic with added corticosteroid into the SI joint
      is a first choice treatment. The aim of this presentation is to provide
      information on our experience with this therapy. MATERIAL AND METHODS: Thirty
      four patients after lumbar spine fusion reported lumbalgia different form pain
      before surgery. In 14 (41%) of them, pain in one of the SI joints was diagnosed
      as the cause. This group included 12 women and two men at an average age of 56
      (range, 47 to 68) years. Ten patients underwent lumbosacral fixation and four had
      segmental ("floating") lumbar spine fusion. All patients experienced lumbalgia at
      more than 3 months following surgery, at 8 months on the average (range, 4 to 12
      months). None of them had SI joint pain before surgery. The diagnosis was based
      on specific manoeuvres on physical examination of the joint. Each patient was
      given an injection of 20 mg (0.5 ml) Methylprednisolone (Depo-Medrol(r), Pfizer,
      Puurs, Belgium) and 4.5 ml 1% Mesocain (Zentiva, Praha, CR).They were inquired as
      to pain relief 24 h later and then at 1, 3 and 6 months after injection.
      Subjective feelings were assessed by a visual analogue scale (VAS). The results
      were analysed using descriptive statistics. RESULTS: All patients reported pain
      relief within 24 h of injection, but not its complete resolution. The average VAS
      score before and after the blockage of the SI joint was 9.1 points (8-10) and 4.8
      points (2-7), respectively; this implies improvement by an average of 4.3 points
      (1-6), i.e., approximately by 47.3% (12.5-62.5). The duration of effects varied
      greatly from patient to patient. The average interval between injection and pain
      recurrence lasted for 5 weeks (1-28). Most frequently, relief was experienced for
      2 weeks, or for 6.8 weeks with the standard deviation included. DISCUSSION
      Sacroiliac joint dysfunction is a very frequent cause of lumbalgia, particularly
      after lumbar spine surgery. Physical therapy may not always be effective. SI
      joint arthrodesis is indicated only in rare cases. One of the few possibilities
      of pain relief involves intra-articular injection of an anaesthetic with
      corticosteroid for booster effect. The treatment of SI joint blockage after
      spinal fusion has recently been dealt with in three reports in the international
      literature; their conclusions are in accordance with the results of this study.
      CONCLUSIONS: Lumbar spine stabilisation surgery may result in overloading the SI
      joints as the "adjacent segments". An intra-articular injection of anaesthetic
      can be considered a reliable method for ascertaining the SI joint as the source
      of a patient's problems. However, even with corticosteroid added, pain relief is
      not usually long-lasting.

PMID- 21888846
TI  - [Arthroscopic technique using crossed K-wires for avulsion fractures of
      intercondylar eminence in children].
AB  - PURPOSE OF THE STUDY: Avulsion fractures of the intercondylar eminence (ICE) of
      the tibia have become increasingly frequent in older school age. Due to recent
      advances in arthroscopic techniques, it is now possible to treat them by
      minimally invasive methods. This retrospective study presents evaluation of
      clinical outcomes of an arthroscopic technique using crossed K-wires. MATERIAL:
      Thirty-five patients with ICE avulsion fracture, 17 girls and 18 boys at an
      average age of 13 years (7-18), were included in this study. All were indicated
      for surgical treatment on the basis of radiographic evidence of McKeever type II
      and III fractures. METHODS: The technique of arthroscopic reduction and fixation
      with crossed K-wires was used. The clinical evaluation of knee stability
      (anterior drawer test and Lachmann s-test) was made by one clinician. The
      modified Tegner-Lysholm score was assessed. RESULTS Of the 35 patients, 26 (74%)
      had minimal knee instability (anterior drawer up to 5 mm), two patients were
      primarily converted to open reduction with good results, and three (8.5%)
      experienced temporary knee instability (anterior drawer of 5-10 mm) that resolved
      spontaneously within 24 months of surgery. Four patients (11.5%) had symptoms of
      persistent residual instability (anterior drawer more than 10 mm) and were
      indicated for anterior cruciate ligament reconstruction at a later stage. The
      average Tegner-Lysholm scores were 86.3/100 and 98.6/100 at 6 and 24 months,
      respectively. DISCUSSION At the present time at our department, McKeever type II
      and III avulsion fractures of the intercondylar eminence are indicated for
      minimally invasive surgical treatment. By exact reduction it is possible to
      decrease the risk of post-operative knee instability. The current trend is the
      use of arthroscopy-assisted minimally invasive techniques such as the method of K
      wire fixation described here. CONCLUSIONS: Arthroscopic surgery for ICE avulsion
      fractures shows good results, is associated with low post-operative risks, is
      minimally invasive and easy to reproduce. It can be recommended as the method of
      choice for treating ICE avulsion injury in children.

PMID- 21888847
TI  - [Patella alta in cerebral palsy patients].
AB  - PURPOSE OF THE STUDY: The absence of active knee extension in cerebral palsy
      patients is often due to elevation of the patellar ligament causing the patella
      to run outside the intercondylar groove. Distal patellar realignment can be
      achieved by either patellar ligament shortening or transposition of the patellar
      ligament distally. MATERIAL: In the 1992-2008 period we indicated 95 knees for
      the distal realignment procedure involving a bone block in children 12 to 18
      years old, and 46 knees in children aged between 8 and 16 years for shortening of
      the patellar ligament using the method of rafage in the early period, and
      modified plication from 2003. METHODS: Clinical and radiographic findings were
      evaluated pre-operatively and at 6 weeks, 6 months and 1 year after surgery. In
      the cases treated by patellar ligament shortening, the Insall-Salvati index was
      assessed post-operatively. Physical examination included local findings and the
      patient's ability to change locomotion. RESULTS: Improved locomotion and
      maintenance of knee extension during standing and walking were recorded in 89 of
      the 95 knees with distal patellar realignment (93.68%) and in 40 of the 46 kness
      with patellar ligament shortening (86.96%). DISCUSSION: Distal realignment of the
      patellar ligament or its shortening should be indicated as a follow-up treatment
      after muscular balance has been gained at persistent knee joint flexion during
      standing and walking, and the inability of active extension. The distal
      realignment procedure with a bone block should be indicated only after growth
      cessation because otherwise genu recurvatum may develop. Concurrently with this
      procedure, it is necessary to carry out distal realignment of the proximal
      ligament of the rectus femoris muscle. CONCLUSIONS: Shortening of the patellar
      ligament using modified plication or its distal realignment involving a bone
      block are two options for the treatment of patella alta that is indicated in the
      absence of active knee extension in cerebral palsy patients.

PMID- 21888848
TI  - [Surgical therapy of primary hyperparathyrodism in the context of orthopaedic
      diagnosis and treatment: our experiences in 441 patients].
AB  - PURPOSE OF THE STUDY: Primary hyperparathyroidism is an endocrine disorder
      affecting calcium and phosphate metabolism. It is surgically treated by removing
      hyperfunctional parathyroid tissue. The aim of the study was to show, based on
      surgical results, that the introduction of serum calcium screening in orthopaedic
      therapy is effective. The detection of hypercalcemia and diagnosis of primary
      hyperparathyroidism allow for a good timing of endocrine surgery in relation to
      an orthopaedic procedure. MATERIAL AND METHODS: This retrospective study included
      441 patients in the age range of 18 to 83 years who underwent parathyroidectomy
      between 2004 and 2007. Skeletal disorders were diagnosed by clinical,
      radiographic and densitometric examination; calcium levels were measured after
      surgery. Bone repair after parathyroidectomy was followed up by the
      endocrinologist for 1 year. RESULTS: Before surgery, 48 % of the patients had
      skeletal disorders. Adenoma was found in 87 %, double adenoma in 2 %, hyperplasia
      in 10 % and parathyroid carcinoma in 0.5 % of the patients. Complications
      involved transient paresthesia of the recurrent laryngeal nerve (1 %), transient
      hypocalcemia (0.5 %), transient post-operative arrhythmias (0.5 %), temporary
      psychological problems (0.7 %) and post-operative bleeding (0.5 %). None of the
      patients died. Serum calcium levels were as follows: 2.90 +/- 0.01 mmol/L pre
      operatively; 2.44 +/- 0.01 mmol/L on the evening of surgery; 2.30 +/-0.01 mmol/L
      on the 1st day; 2.19 +/- 0.01 mmol/L on the 2nd day; and 2.18 +/- 0.01 mmol/L on
      the 3rd post-operative day. On the 3rd post-operative day most of the patients
      were discharged from the hospital. Normal calcium levels were achieved in 98 % of
      the surgically treated patients. DISCUSSION AND CONCLUSIONS: The study provides
      evidence for the efficiency of calcium screening in primary hyperparathyroidism
      and shows the feasibility of involving endocrine surgery in the course of
      orthopaedic treatment.

PMID- 21888849
TI  - [Resection and reconstruction of the chest wall for primary or metastatic
      tumours].
AB  - PURPOSE OF THE STUDY: The aim of the study was to assess mortality and the
      complication rate after the extensive resection of chest wall tumour and
      subsequent soft tissue reconstruction. We wanted to evaluate the justification
      for major surgery in the group of patients with primary or secondary tumours,
      including those with an advanced stage of disease. MATERIALS AND METHODS: A total
      of 35 patients after major chest wall resection within an eight-year period (2000
      2008) were analysed retrospectively. A major resection was defined as resection
      of 75 cm2 or more of full thickness of the chest wall. There were 19 cases of
      primary malignant tumour of the chest wall, 10 cases of secondary tumour, and 6
      cases of benign or semi-malignant lesions. The chest was stabilised with the help
      of either polypropylene or a double layer mesh of polyester covered with
      polyurethane. For soft tissue reconstruction, a musculocutaneous flap was used in
      18 cases. The number of resected ribs ranged from two to seven. The vertebral
      body was partially resected in four cases, and total sternectomy was performed in
      two cases. This surgery was carried out with potentially curative intent in 30
      (85.7%) and with palliative intent in five patients (14.3%). RESULTS: No post
      operative mortality occurred. The complication rate was 17.1 %. The one-year
      survival rate was 88.6 %. There were seven long-term survivors at 5 or more years
      after resection of the chest wall for soft tissue sarcoma. Local recurrence
      occurred in six patients (17.1%). Neither the type of prosthesis nor the type of
      surgical procedure influenced the complication rate. DISCUSSION: Chest wall
      resection is an established surgical procedure in the treatment of primary chest
      wall tumours and, occasionally, solitary metastatic disease. The groups of
      patients reported in the literature have been heterogeneous and usually small,
      and thus an estimation of the true risk of the major procedure is difficult.
      Three studies involving large patient groups published in the last 11 years have
      shown morbidity in 24.4%, 33.2% and 46.0% of patients and mortality in 7.0%, 3.8%
      and 4.1% of patients, respectively. The results in our group of unselected
      patients are comparable with these studies; however, we did not perform extensive
      procedures like pneumonectomy and chest wall resection, or extended fore quarter
      amputation. CONCLUSIONS Complete resection of the chest wall is feasible even in
      advanced tumours without significant peri-operative morbidity and mortality.
      Major chest wall resection as a palliative procedure remains selective for
      motivated patients in a good physical condition but with low quality of life
      caused by a chest wall tumour.

PMID- 21888850
TI  - [Biomechanical parameters and clinical outcomes of the Oxford Phase III
      unicompartmental knee replacement].
AB  - PURPOSE OF THE STUDY: The kinematics of an intact knee joint and that of a knee
      replacement have been studied in many research centres. In the 1987 radiographic
      study, Bradley, Goodfellow and O'Connor reported the movement of a polyethylene
      insert in patients with unicompartmental Oxford knee replacement. Views with the
      knee at full extension and 90 degrees  of flexion were obtained and the movement
      of the meniscal bearings over this range of flexion was measured. The bearings
      were found to move backwards on the tibia through an average distance of 4.4 mm
      in all 16 patients. This measurement was in agreement with the then valid concept
      of knee biomechanics and a roll-back phenomenon. However, our observations had
      not always agreed with the results of these authors, but gave an impetus for a
      detailed evaluation of our own patient group. The aim of the study was to
      evaluate the dynamic relationship between the components of a unicompartmental
      Oxford knee replacement and elucidate it with the use of recent information from
      the field of biomechanics. A relationship of the obtained kinematic values to
      clinical outcomes was also investigated. Answers to the following hypotheses were
      sought: Would our results be in agreement with the British authors' findings?
      Would clinical outcomes depend on the kinematic properties of knee replacements?
      MATERIAL AND METHODS: The group comprised 33 patients, 23 women and 10 men. They
      all had replacement of the medial compartment of the knee. The construction of
      the unicompartmental Oxford Phase III knee replacement enabled us to locate the
      centre of rotation of the medial femoral condyle in relation to the tibial
      component at flexion and extension of the knee, using radiography. The patients
      were examined in a supine position with the knee at full extension, and
      subsequently views of the knee were obtained at 80 degrees -90 degrees  flexion
      in accordance with the method used by the British authors. The clinical findings
      of knee joints were assessed using the American Knee Society (AKS) scoring system
      (Insall et al.). Pain was rated on the Visual Analogue Scale (VAS). The results
      were statistically evaluated with the t-test and Chi-square test. RESULTS: On
      moving the knee from extension to flexion, movement of the polyethylene insert
      ventrally by an average of 3.4 mm in relation to the tibia was recorded, i.e.,
      "paradoxical" ventral translocation. In the patients with insert movement less
      than or equal to 3 mm, the average AKS score was 89 points, in those with
      movement over 3 mm it was 87 points. The average functional scores were 87 and 83
      points in the patients with movement less than 3 mm and more than 3 mm,
      respectively. The average VAS score was 1.55 in the former and 1.18 in the
      latter. DISCUSSION: The unicompartmental Oxford Phase III knee replacement
      substitutes a flexion femoral facet and eliminates the role of an extension
      femoral facet. This is the reason why, at knee extension between -5 degrees  and
      +20 degrees , the centre of rotation of the medial femoral condyle is in the
      centre of the flexion facet and not in that of the extension facet. When the
      stabilising functions of the extension tibial facet in the ventral direction and
      of the dorsal part of the insert in the dorsal direction are missing, the
      position of the contact surface centre becomes much dependent also on the
      strength and direction of external forces acting in the knee joint vicinity.
      CONCLUSIONS: The kinematic parameters of the unicompartmental Oxford Phase III
      knee replacement investigated in our group differed from the findings of the
      British authors. However, neither the magnitude nor the direction of movement had
      any effect on the clinical outcome of knee arthroplasty.

PMID- 21888851
TI  - [Aseptic necrosis of the capitulum of the humerus (Panner's disease) treated by
      solid chondrograft implantation].
AB  - The authors present the case of aseptic necrosis of the humeral capitulum in a
      top female gymnast. She was referred to our department with the diagnosis of
      aseptic necrosis already made and after repeated arthroscopic treatment of the
      elbow including removal of a loose body in another institution. Exercise-related
      pain and swelling of the elbow became permanent and did not allow her to pursue
      her sports activities. After thorough examination, the treatment by implantation
      of autologous cultured chondrocytes, as a solid chondrograft, was chosen. At the
      first stage of arthroscopic surgery, a loose body was removed and a sample of
      healthy cartilage from an articular region not subject to strain was collected.
      The sample was sent to the Tissue Bank for cultivation and chondrocyte formation
      into a solid chondrograft, a procedure taking 4 to 5 weeks. At the second stage,
      the chondrograft was implanted into the lesion site and fixed with tissue glue
      (Tissucol). The arm was immobilised in a plaster cast for 4 weeks. The patient
      was followed up clinically and examined with magnetic resonance imaging at 6
      month after implantation. The examination showed full graft integration and the
      arm's return to full mobility without pain at exercise. Even with this rare
      lesion site within the elbow joint, the implantation of a solid chondrograft
      proved to be a method achieving very good outcomes.

PMID- 21888853
TI  - Serum cystatin C levels in normal pregnancy.
AB  - AIM: The aim of this study was to determine the levels of cystatin C, creatinine
      and creatinine clearance in different trimesters of uncomplicated pregnancy in
      women with normal kidney function. SUBJECTS AND METHODS: A total of 109 pregnant
      women were included: group 1 - 38 women (average age 29.63 +/- 4.3 y) in the
      first trimester, Group 2 - 32 women (average age 33.56 +/- 5.95 y) in the second
      trimester and Group 3 - 39 pregnant women (average age 30.1 +/- 6.95 y) in the
      third trimester. Serum cystatin C was determined by the PENIA method (Particle
      Enhanced Nephelometric Immuno-Assay), using Behring tests (Behring Diagnostics
      GmbH, Marburg, Germany). Results were statistically analyzed using the ANOVA.
      RESULTS: A statistically significant increase in serum cystatin C level was found
      in the third trimester of pregnancy (0.69 +/- 0.16 mg/l vs. 0.78 +/- 0.26 mg/l
      vs. 1.21 +/- 0.30 mg/l). CONCLUSION: It appears that cystatin C is not a reliable
      marker of kidney function in pregnancy and that its increase is connected with a
      combination of several factors, including endotheliasis, hormonal influence and
      glomerular filtration rate (GFR) alterations.

PMID- 21888852
TI  - Cytokines in acute kidney injury (AKI).
AB  - In acute kidney injury (AKI), many cytokines are released by leukocytes and renal
      tubular cells in the injured kidney and are important components of both the
      initiation and extension of inflammation. Cytokines are 1) produced by the kidney
      and mediate AKI, 2) produced by the kidney, released into the blood or urine and
      serve as biomarkers of AKI, and 3) produced by the kidney or other organs in AKI
      and mediate or protect against distant organ injury. Further understanding of the
      role of cytokines in AKI may result in therapeutic approaches like cytokine
      inhibition that may reduce the degree of kidney injury itself, as well as
      deleterious effects of kidney injury on other organs.

PMID- 21888854
TI  - Kidney biopsy in patients with diabetes mellitus.
AB  - BACKGROUND: The clinical consequences of the results obtained by kidney biopsy in
      patients with diabetes mellitus Type 1 or Type 2 have been controversial. Our
      study was conducted to assess clinical symptoms and histological diagnoses in
      patients with diabetes mellitus Type 1 and Type 2 undergoing kidney biopsy.
      DESIGN, SETTING AND PATIENTS: Observational study. The study included data from
      567 consecutive renal biopsies of patients with diabetes mellitus Type 1 or 2 and
      chronic kidney disease (CKD) examined by standard histopathological procedures.
      The main outcome measures were incidence of diabetic nephropathy (DN) and
      glomerulonephritis (GN), predictors for the presence of both DN or GN. RESULTS:
      Approximately 70% of patients with diabetes mellitus Type 1 or 2 and evidence for
      CKD had DN. Glomerular diseases present in approximately 30% of patients with
      diabetes were predominantly immune complex GN and secondary focal
      glomerulosclerosis, followed by IgA-GN, which was associated with microhematuria
      (p = 0.01) and hypertension (p = 0.04). Only a minority had membranous GN, which
      was associated with nephrotic syndrome (p = 0.004). Progressive CKD predicted the
      presence of GN in diabetes mellitus Type 2 (r = -0.98; p = 0.02). CONCLUSION: GN
      is not uncommon in patients with diabetes and evidence for CKD. Kidney biopsy
      should therefore be considered in patients with diabetes and progressive CKD.

PMID- 21888855
TI  - Long-term prognosis for Chinese adult patients with acute postinfectious
      glomerulonephritis.
AB  - AIMS: The long-term prognosis for adults with acute postinfectious
      glomerulonephritis (APIGN) is under debate. This study was designed to
      investigate the long-term renal outcome of adult APIGN. MATERIALS AND METHODS: A
      total of 64 adults with APIGN were identified and divided into two groups: acute
      poststreptococcal glomerulonephritis (APSGN) group and acute nonstreptococcal
      postinfectious glomerulonephritis (nonstreptococcal APIGN) group. For the purpose
      of outcome analysis, 49 patients with a follow-up of >= 12 months were included.
      Univariate and multivariate analyses were performed for prognostic factors.
      RESULTS: Nephrotic syndrome was more frequently seen in nonstreptococcal APIGN
      patients. At the time of biopsy, the mean proteinuria of the two groups was 1.82
      +/- 2.14 and 4.21 +/- 4.39 g/d, respectively (p = 0.005). There was no
      significant difference between the two groups on microscopy. Among the 49
      patients with >= 12 months of follow-up, the complete remission rate was 85.7%,
      and the incidence of chronic renal failure and endstage renal disease (ESRD) was
      6.1% and 4.1%, respectively. The complete remission rate of the APSGN group was
      higher than that of the nonstreptococcal APIGN group. Univariate analysis showed
      that the prognostic factors were age, underlying disease, proteinuria, tubular
      damage and C1q deposits. In multivariate analysis, underlying disease was the
      only significant and independent inverse correlate of complete remission.
      CONCLUSIONS: The long-term prognosis for young Chinese adults with APIGN is
      optimistic if there is no underlying disease. The renal outcome for patients with
      APSGN is better than for patients with nonstreptococcal APIGN.

PMID- 21888856
TI  - Prevalence of abnormal in vitro closure time using the Platelet Function Analyzer
      100 in chronic kidney disease patients and analysis of associated factors.
AB  - AIM: Platelet Function Analyzer- 100 evaluates platelet function by determining
      time to occlusion of an aperture in a membrane coated with collagen and
      epinephrine (CEPI) or collagen and ADP (CADP) during the flow of citrated whole
      blood. We sought to determine prevalence of abnormal in vitro closure time (CT)
      in chronic kidney disease (CKD) patients and to analyze associated factors.
      MATERIALS AND METHODS: CEPI-CT (normal, 82 - 182 sec in Korean), CADP-CT (normal,
      62 - 109 sec), CBC, serum creatinine (Cr) and blood urea nitrogen (BUN) were
      measured in CKD patients, 30 with Stage I, 36 with Stage II, 30 with Stage III,
      56 with Stage IV, 283 with Stage V (79 with pre-dialysis Stage V, 130 on chronic
      hemodialysis (CHD), and 74 on chronic peritoneal dialysis (CPD)). Estimated
      glomerular filtration rate (eGFR) was calculated with a MDRD equation. RESULTS:
      Abnormal CEPI-CT and CADP-CT occurred in < 15% of Stage I - III, 20% of Stage IV,
      and 41% and 54%, respectively, of Stage V patients. There were no differences in
      prevalence of abnormal CEPI-CT and CADP-CT among predialysis Stage V, CHD and CPD
      patients. CEPI-CT and CADP-CT were correlated with BUN, Cr and platelet counts in
      predialysis patients, and with platelet counts in dialysis patients, and CEPI-CT
      was correlated with BUN, Cr in CPD patients. Neither, however, was correlated
      with age, gender, hemoglobin or hematocrit. CONCLUSION: Prevalence of abnormal in
      vitro CT increases as stage worsens in CKD patients. In vitro CT is correlated
      with BUN, Cr and platelet counts in predialysis and total CKD patients.

PMID- 21888857
TI  - Clinical significance of FGF-23 measurement in dialysis patients.
AB  - AIMS: Considering the growing relevance of fibroblast growth factor-23 (FGF-23)
      in the pathogenesis of chronic kidney disease bone and mineral disorder (CKD
      MBD), an analysis was performed to determine the relative importance of C
      terminal (cFGF-23) and intact (iFGF-23) assays in assessing CKD-MBD status in the
      first place and the relationship between FGF-23 and mortality as a secondary aim.
      METHODS: In 77 patients (15 peritoneal dialysis and 62 hemodialysis), levels of
      calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin- D (25D), 1,25D,
      FGF-23 (C-terminal and intact molecule) were measured and their correlations were
      analyzed. The relationship between FGF-23 levels and patient survival was also
      analyzed. RESULTS: A significant correlation was found between cFGF-23 and 1,25D,
      PTH and 25D while iFGF-23 was significantly correlated with phosphate, 25D and
      PTH. PTH and 1,25D were independent predictors of cFGF-23, while for iFGF-23
      independent predictors were phosphate and 25D. No significant relationship was
      found between FGF-23 and mortality. CONCLUSIONS: C-terminal or intact FGF-23
      levels are weakly correlated and thus not clearly indicative of FGF-23 effects on
      PTH, P and vitamin D metabolism in dialysis patients. Assays for cFGF-23 and iFGF
      23 showed a good correlation, but the intact molecule was not superior in
      defining interactions with CKD-MBD molecules. Measuring FGF-23 on a regular basis
      with the current assays in CKD and dialysis patients does not yet seem clinically
      useful.

PMID- 21888858
TI  - Hemoglobin level variability in hemodialysis patients treated with epoetin-beta
      during 1 year.
AB  - AIM: This analysis was performed to assess the prevalence and the factors
      associated with hemoglobin (Hb) variability during treatment with erythropoiesis
      stimulating agents (ESA) in France. METHODS: Hb variability was evaluated in a
      subgroup of hemodialysis (HD) patients of the French cohort DiaNE. Eligible
      patients had received epoetin-beta at least 6 months before entering DiaNE, 12
      months during DiaNE and had no missing monthly Hb measurements. Up and down
      excursions (Hb variations > 1.5 g/dl with duration > 8 weeks) were assessed.
      RESULTS: Of the 499 patients evaluated in this analysis, 295 (59%) had Hb levels
      inside the target range of 11 - 13 g/dl at baseline. The number of patients with
      constantly stable Hb level inside the target range decreased from baseline to
      27.5% at 6 months and 10.8% at 12 months. More than 70% of patients experienced
      Hb variability. The number of excursions was 1.7 +/- 0.8 per patient/year. The
      amplitude of up excursions was 2.8 +/- 1.0 g/ dl with a duration of 14.7 +/- 4.7
      weeks. The amplitude of down excursions was 2.6 +/- 0.9 g/dl with a duration of
      14.5 +/- 4.6 weeks. The main factors associated with Hb variability were number
      of epoetin-beta dose changes, adverse events and iron therapy changes.
      CONCLUSION: Hb variability is frequent in French ESA-treated HD patients and
      closely related to practices. Further efforts are needed to improve anemia
      management.

PMID- 21888859
TI  - The effect of calcineurin inhibitors on endothelial and platelet function in
      renal transplant patients.
AB  - BACKGROUND/AIM: Posttransplant cardiovascular mortality is still an important
      problem in renal transplant patients. In addition to conventional coronary risk
      factors, coagulation abnormalities play a key role in the hypercoagulable state
      observed in transplanted patients. Though renal transplantation eliminates
      cardiovascular disease risk factors by restoring renal function, it introduces
      new cardiovascular risks derived, in part from immunosupressive medications. We
      aimed to assess the effect of calcineurin inhibitors on endothelial function,
      platelet activation and aggregation in renal transplant patients. METHODS: 62
      renal transplant were studied. Staging was performed according to
      immunosuppression regimen. Group 1 (n = 37) were treated with
      cyclosporine/mycophenolate mofetil/methylprednisolone and Group 2 (n = 25) were
      treated with tacrolimus/mycophenolate mofetil/methylprednisolone. The control
      group consisted of 16 healthy subjects (Group 3). Hematological and biochemical
      tests, asymmetric dimethyl arginine (ADMA), sP-selectin levels and platelet
      aggregation tests were studied. RESULTS: ADMA levels were higher in Group1 and
      statistically significant differences were observed compared with those of Group
      2 and Group 3 (p < 0.05). Platelet aggregation values induced by all agonists
      (Adenosine diphosphate (ADP), epinephrine, ristocetin, collagen) were lower in
      Group 1 than Group 2 and Group 3, but the difference did not reach statistical
      significance (p > 0.05). There was a negative correlation between cyclosporine
      level and platelet aggregation values induced by ADP (r = -0.43, p < 0.01),
      ristocetin (r = -0.40, p < 0.05), epinephrine (r = -0.41, p < 0.05), and collagen
      (r = -0.43, p < 0.01). sP-selectin levels were appreciably higher in Group 1 and
      statistically significant differences were observed compared with those of Group
      2 (p < 0.05) and Group 3 (p < 0.01). CONCLUSION: The results of our study suggest
      that CsA induces platelet activation without inducing platelet aggregation.
      Endothelial dysfunction due to vascular endothelial damage reflected by increases
      in ADMA values may increase the tendency for thrombotic events in patients who
      had undergone renal transplantation.

PMID- 21888860
TI  - Comparative study of percutaneous nephrostomy using catheters with and without
      locking strings.
AB  - BACKGROUND: Although it is generally felt that a catheter with a locking string
      can achieve better fixation and thus prevent catheter displacement, no formal
      study has ever substantiated this. METHODS: We retrospectively reviewed the
      charts from 80 patients (mean age of 64.6 +/- 14.76 y) who underwent percutaneous
      nephrostomy (PCN) over a 1-year period. RESULTS: Most patients had catheters
      without locking strings and only 17 patients (21.3%) had catheters with locking
      strings. The median duration of catheter placement was 29 days (interquartile
      range 14 - 57 d). There were no significant differences in patients'
      characteristics or catheter outcomes between catheters with and catheters without
      locking strings (p > 0.05). In addition, no significant difference in the
      catheter 90-day survival between catheter types was found (log rank test, p =
      0.638). On univariate analysis, tumor as an indication for PCN (p = 0.018),
      obstruction (p = 0.021) and displacement (p = 0.007) were associated with reduced
      catheter survival. The multivariate analysis indicated that tumor as an
      indication for PCN (HR: 0.28, 95% CI: 0.13 - 0.63, p = 0.002), obstruction (HR:
      0.25, 95% CI: 0.08 - 0.77, p = 0.015) and catheter displacement (HR: 0.09, 95%
      CI: 0.03 - 0.31, p < 0.001) were independent hazard factors for reduced catheter
      90-day survival. CONCLUSION: No significant difference in either complication
      rate or 90-day survival was found between catheters with or without locking
      strings. These findings may prove helpful to the clinician in deciding the type
      of catheter to use during PCN.

PMID- 21888862
TI  - WT1 mutations may be a cause of severe renal failure due to nephroblastomatosis
      in Wilms' tumor patients.
AB  - Wilms' tumor suppressor gene (WT1) encodes a transcription factor required for
      normal development of the genitourinary system. Germline WT1 mutations have been
      described in a wide spectrum of pathological conditions, including kidney
      diseases, genital abnormalities and Wilms' tumor. Here we report a 4-year-old
      male patient who presented with bilateral cryptorchidism, Wilms' tumor,
      nephroblastomatosis and renal failure without nephrotic proteinuria. Sequence
      analysis of the WT1 gene demonstrated a constitutional heterozygous nonsense
      mutation in exon 7, which leads to a truncation of the WT1 protein at the zinc
      finger 1. In the DNA of the tumor, we observed the same mutation in
      homo/hemizygosity. Given the requirement of WT1 for normal development, the WT1
      mutation is likely to be responsible for the nephroblastomatosis and, in
      consequence, for the severe renal failure observed in our patient. This finding
      extends the spectrum of kidney diseases related to WT1 mutations and points to
      the need to screen for this gene in children with genitourinary abnormalities and
      Wilms' tumor because of the associated risk of nephroblastomatosis and renal
      failure in those carrying WT1 mutations.

PMID- 21888861
TI  - Cinacalcet reduces plasma intact parathyroid hormone, serum phosphate and calcium
      levels in patients with secondary hyperparathyroidism irrespective of its
      severity.
AB  - AIMS: To evaluate the relationship between the severity of secondary
      hyperparathyroidism (SHPT) - defined in terms of baseline plasma intact
      parathyroid hormone (iPTH) level - and the magnitude of response to cinacalcet.
      MATERIALS AND METHODS: In this post hoc analysis, data were pooled from three
      randomized, placebo-controlled trials in which dialysis patients with iPTH >= 300
      pg/ml were dose-titrated with cinacalcet or placebo in addition to conventional
      treatment to achieve iPTH <= 250 pg/ml. In 953 patients analyzed (cinacalcet,
      545; placebo, 408), baseline iPTH levels were categorized in 100 pg/ml intervals
      (300 - >= 1,000 pg/ml), and the impact of baseline iPTH on changes in iPTH,
      phosphate (P), calcium (Ca) and calcium- phosphate product (Ca * P) was
      evaluated. RESULTS: Cinacalcet reduced iPTH (47% reduction), P (9%), Ca (7%), and
      Ca * P (15%) across all subgroups. For patients receiving cinacalcet, the mean
      percentage reduction from baseline in iPTH varied from 35 to 55%, being
      consistently decreased across the severity subgroups. The mean absolute change in
      iPTH was more pronounced in patients with higher baseline iPTH levels,
      particularly in the >= 1,000 pg/ml subgroup vs. the other subgroups. However, as
      baseline iPTH levels increased, iPTH <= 250 pg/ml was achieved in fewer patients.
      A trend towards greater absolute change from baseline was observed for P in
      patients with more severe disease (iPTH >= 800 pg/ml) treated with cinacalcet
      compared with patients with less severe disease (iPTH 300 - < 800 pg/ml).
      CONCLUSIONS: Cinacalcet lowers plasma iPTH and serum P, Ca and Ca * P levels in
      dialysis patients with SHPT, regardless of disease severity. Patients with more
      severe disease experienced greater reductions in PTH and P, but fewer achieved
      iPTH <= 250 pg/ml by the efficacy assessment phase. Use of cinacalcet when
      baseline PTH is lower may result in more stable control of SHPT and help to
      control bone and mineral alterations.

PMID- 21888863
TI  - A case of renal infarction associated with elevated factor VIII level.
AB  - Elevated factor VIII level has recently been shown to be associated with
      increased risk of thrombosis. We report here a case of renal infarction in
      association with elevated factor VIII level. The patient presented with a three
      day history of flank pain. Laboratory studies on presentation showed an elevated
      serum creatinine concentration and microscopic hematuria. He was found to have
      bilateral pulmonary emboli and left common femoral vein thrombosis; imaging
      studies showed evidence of renal arterial thrombosis with infarction.
      Hypercoagulability assessment showed an elevated factor VIII level. He was
      treated with heparin and warfarin with significant improvement in his renal
      function. Consideration should be given to measurement of factor VIII level as a
      part of the workup of unexplained thrombo-embolic events.

PMID- 21888864
TI  - The incidence of fatal kidney biopsy.

PMID- 21888865
TI  - A survey on clinical study participation and study infrastructure at non
      university hospitals in Germany.
AB  - OBJECTIVE: In order to participate in multicenter clinical trials a fair amount
      of infrastructure and human resources has to be provided by hospitals. Therefore
      clinical trials are carried out predominantly in university hospitals. Data
      concerning participation in clinical trials and the infrastructure of study
      centers in non-university hospitals in Germany do not exist. A survey was thus
      conducted to evaluate the current status of clinical study performance in non
      university hospitals. MATERIALS AND METHODS: A questionnaire comprising 10
      questions covering hospital infrastructure, local study history, and the
      individual interest in performing studies was sent to 790 non-university
      hospitals in Germany. RESULTS: 58.7% of questionnaires were returned for
      evaluation. 74.1% of nonuniversity hospitals participate in clinical studies.
      Hospital size is a significant predictor of study participation. 25.5% of
      hospitals have established a multidisciplinary study center. 86.2% have a
      certified study nurse and in 34.5% this nurse is the only person running the
      study center. Only 25.5% of hospitals were not interested in participating in
      clinical studies at all, even if an individual tailored concept were to be
      offered. CONCLUSIONS: The demand for more hospitals to participate in clinical
      trials is urgent since high quality studies are a fundamental part of clinical
      research. Even though 75% of non-university hospitals in Germany already
      participate in clinical trials, it may be possible to increase this number. In
      addition by establishing and developing study centers in hospitals the quality of
      studies will presumably rise, and due to the concentration of study resources,
      the number of clinical trials may increase.

PMID- 21888866
TI  - Prescriber adherence to pharmacokinetic monitoring service recommendations for
      aminoglycoside dosing and the risk of acute kidney injury.
AB  - OBJECTIVE: The importance of adherence to aminoglycoside dosing recommendations
      by a pharmacokinetic monitoring service for preventing acute kidney injury (AKI)
      is unknown. We aimed to examine the association between AKI and discordance in
      aminoglycoside dosing between physician orders and recommendations by a
      pharmacokinetic monitoring service. MATERIALS: We utilized 2000 - 2003 data from
      a large quaternary care academic medical center, including: hand-written
      pharmacokinetic monitoring service recommendations; computerized physician order
      entry inpatient medication orders; and electronic inpatient laboratory orders and
      results. METHODS: We conducted a case-control study, nested within users of
      intravenous aminoglycosides. Outcomes of interest were cases of AKI, as
      determined by changes in serum creatinine. Exposures of interest were
      discordances between pharmacokinetic monitoring service recommendations and
      physician orders in the past 2 days with regard to total daily aminoglycoside
      dose. RESULTS: Most patients received once-daily or less frequent aminoglycoside
      dosing. In 1,414 evaluable aminoglycoside courses, 220 patients developed AKI,
      for a cumulative incidence of 15.6%. We identified 690 controls, matched these to
      220 cases, and found adjusted odds ratios of 0.72 (95% CI: 0.37 - 1.39) for
      overdose discordance and of 0.83 (0.51 - 1.34) for underdose discordance,
      suggesting that discordance in dosing is not associated with AKI. CONCLUSION: Non
      adherence to dosing recommendations for aminoglycosides was not associated with
      risk of AKI in a setting primarily of once-daily aminoglycoside administration.

PMID- 21888868
TI  - Influence of common cardiac drugs on gastroesophageal reflux disease: multicenter
      questionnaire survey.
AB  - BACKGROUND: Although gastroesophageal reflux disease (GERD) causes noncardiac
      chest pain mimicking angina pectoris, systemic studies surveying the effects of
      common cardiac drugs on symptomatic GERD are rare. METHODS: To investigate the
      drugrelated GERD, this multicenter trial enrolled 201 consecutive cardiac
      outpatients (69.7 +/- 10.5 y) after obtaining written informed consent. They were
      assessed using the Frequency Scale for Symptoms of GERD (F-scale) to screen for
      GERD with a cut-off value of 8.0. Clinical background was obtained from medical
      records. Gastric medicine was empirically administered at the discretion of the
      attending physician. F-scale score and incidence of GERD were analyzed
      individually in relation to background and prescription. RESULTS: The average F
      scale score did not correlate with gender, age or underlying diseases. F-scale
      score was elevated significantly (p = 0.006) by administration of calcium channel
      blockers to the patients treated with gastric medicine, suggesting that calcium
      channel blockers exacerbate the possibly preexisting GERD. Incidence of GERD
      within 2 months after starting warfarin tended to be greater than that at other
      durations (p = 0.087). Patients showing a high score (>= 8.0) suggestive of GERD
      showed a correlation with the combined administration of calcium channel blockers
      (OR = 3.19; 95% CI of 1.01 - 10.11; p = 0.049) and warfarin (OR = 3.05; 95% CI of
      1.00 - 9.27; p = 0.049) in the best logistic model. CONCLUSION: Although larger
      cohort is required, this survey demonstrates that the combination of calcium
      channel blockers and warfarin is an independent risk factor for GERD.

PMID- 21888867
TI  - The effect of beta-adrenergic blockade and COX-2 inhibition on healing of colon,
      muscle, and skin in rats undergoing colonic anastomosis.
AB  - OBJECTIVE: COX inhibitors and beta-adrenergic blockers were recently shown to
      reduce cancer progression in animal models through various mechanisms. These
      include the prevention of immune suppression during the critical perioperative
      period, and the preclusion of direct promoting effects of catecholamines and
      prostaglandins on malignant tissue growth. To assess the safety of such
      pharmacological treatments in the context of oncologic surgery, the current study
      evaluates wound healing efficacy in the skin, muscle, and colon tissues in rats
      undergoing colonic anastomosis. METHODS: F344 rats were treated daily with a COX
      2 inhibitor (etodolac), a beta-adrenergic blocker (propranolol), both drugs or
      vehicles. All rats underwent skin punch biopsy, and half were also subjected to
      laparotomy and colonic anastomosis. Tensile strength of the abdominal wall and
      colonic bursting pressure were assessed on Days 3, 7, and 30 postoperatively, and
      skin biopsy site healing was scored on Days 2, 4, and 6 postoperatively. RESULTS:
      None of the drug treatments produced any deleterious effects along the expected
      course of tissue healing. On Day 30, colon bursting pressure showed an abnormal
      strengthening in animals undergoing anastomosis compared to non-operated animals,
      across all drug treatments. This abnormal strengthening was attenuated by
      etodolac. In the skin, surgery reduced healing rate, irrespective of drug
      treatments. CONCLUSIONS: Effective doses of etodolac and propranolol caused no
      negative effects on wound healing processes in rats. The apparent safety of such
      treatments, together with their potential clinical benefits, suggests the
      incorporation of these treatments in oncologic patients undergoing curative tumor
      resection.

PMID- 21888869
TI  - Pharmacokinetics and pharmacodynamics of tonapofylline in subjects with severe
      renal impairment and in elderly subjects.
AB  - OBJECTIVE: The study was conducted to characterize the pharmacokinetics and
      pharmacodynamics of tonapofylline in subjects with severe renal impairment and in
      elderly subjects. METHOD: Subjects with severe renal impairment were matched
      demographically with healthy subjects. Elderly subjects with normal renal
      function for their ages were also enrolled. All subjects (n = 8 per group)
      received a single intravenous administration of tonapofylline at 1 mg/kg.
      RESULTS: The pharmacokinetics of tonapofylline was not significantly different in
      subjects with severe renal impairment, or in elderly subjects, as compared to
      healthy subjects. Among all pharmacokinetic parameters, the only statistically
      significant difference was observed for Cmax between the healthy and the severe
      renal impairment groups, which was 21% and considered clinically insignificant.
      Pharmacodynamic assessment demonstrated the natriuretic effects of tonapofylline
      across groups, with little accompanying kaliuresis. No change in renal function
      occurred after single dose of tonapofylline, despite substantial increases in
      excretion of urinary sodium. Single 1 mg/kg intravenous administration of
      tonapofylline was generally safe. CONCLUSION: The pharmacokinetics of
      tonapofylline in subjects with severe renal impairment and elderly subjects with
      normal renal function for age is similar to that in healthy subjects. It has been
      demonstrated in all groups that tonapofylline has natriuretic effects and is able
      to maintain renal function, which can be beneficial to patients with congestive
      heart failure.

PMID- 21888870
TI  - Comparative bioavailability study of cefuroxime axetil (equivalent to 500 mg
      cefuroxime/tablet) tablets (Zednad(r) versus Zinnat(r)) in healthy male
      volunteers.
AB  - This study was performed to investigate the bioequivalence of cefuroxime axetil
      tablets between a generic test product (A) Zednad(r) Tablet (500 mg cefuroxime/
      tablet, Diamond Pharma, Syria), and the Reference Product (B) Zinnat(r) Tablet
      (500 mg cefuroxime/tablet, GlaxoSmithKline, Saudi Arabia). The bioavailability
      study was carried out for 24 healthy male volunteers. The subjects received 1
      Zednad(r) Tablet (500 mg/ tablet) and 1 Zinnat(r) Tablet (500 mg/tablet) in a
      randomized, two-way crossover design fashion on 2 treatment days, after an
      overnight fast of at least 10 h, with a washout period of 7 days. 24 volunteers
      plus 2 alternatives completed the crossover. The bioanalysis of clinical plasma
      samples was accomplished by HPLC method, which was developed and validated in
      accordance with international guidelines. Pharmacokinetic parameters, determined
      by standard non-compartmental methods, and ANOVA statistics were calculated using
      SAS Statistical Software. The significance of a sequence effect was tested using
      the subjects nested in sequence as the error term. The 90% confidence intervals
      for the ratio between the test and reference product pharmacokinetic parameters
      of AUC0->t, AUC0->infinity, and Cmax were calculated and found to be within the
      confidence limits of 80.00 - 125.00% for AUC0->t, AUC0->infinity and Cmax. The
      study demonstrated that the test product (A) was found bioequivalent to the
      reference product (B) following an oral dose of 500 mg tablet. Therefore, the two
      formulations were considered to be bioequivalent.

PMID- 21888871
TI  - Mental contamination: the perpetrator effect.
AB  - In order to test the proposition that imagining carrying out an unacceptable non
      consensual act can evoke contamination-related feelings in the perpetrator, 4
      connected experiments were carried out involving male students. The effects of
      the experimental procedure were enhanced by the introduction of a theme of
      betrayal which boosted the feelings of contamination and urges to wash. The non
      consensual scenarios were followed by substantial increases in negative emotions,
      notably shame, disgust and guilt, and these increases were boosted over
      successive enhancements of the procedure. Overall the results show that
      perpetrators of (imagined) unacceptable acts report a range of negative emotions
      and feelings of dirtiness. The main conclusion of this research is that imagining
      an unacceptable, non-consensual act can produce feelings of contamination. It is
      an experimental illustration of mental contamination, that is, contamination
      which is evoked by a mental event without any contact with a tangible
      contaminant.

PMID- 21888872
TI  - Examining waterborne and dietborne routes of exposure and their contribution to
      biological response patterns in fathead minnow (Pimephales promelas).
AB  - The objectives of the current study were: (i) to gain a better understanding of
      the relative importance of water and diet as routes of exposure causing toxicity
      in fathead minnow (FHM) exposed to metal mining effluents (MME) using a full
      factorial water/food experimental design (Experiment 1), and (ii) to assess
      differences in the effects of food quality on toxicity by comparing FHM fed both
      a live and frozen diet of Chironomus dilutus (Experiment 2). The results showed
      significant increases in general water quality parameters (e.g., hardness,
      conductivity) and various metals in the effluent treatment waters compared to
      control waters, with maximum increase seen in the multi-trophic streams. Metals
      accumulation (Rb, Al, Se, Sr, Tl, Ce, Co, Cu, Pb) effects of both waterborne and
      multi-trophic exposures were significant in one or more fathead minnow tissue
      type (muscle, gonads, liver, larvae) relative to those in the control systems.
      Condition factor and liver somatic index (LSI) of FHM were also significantly
      affected in both exposures by one or both routes of exposure (water and/or diet).
      In addition, cumulative total egg production and cumulative spawning events were
      significantly affected by both waterborne and dietborne exposures, with maximum
      effect found in the multi-trophic streams. These results suggest that under
      environmentally relevant exposure conditions, trophic transfer of metals may lead
      to greater reproductive effects and increased metal toxicity in fish. It also
      indicates that metals are assimilated in tissues differently depending on the
      quality of the food (live vs. frozen). Overall, it appears that the multi-trophic
      bioassay provides an important link between the laboratory and field, which may
      allow for a more realistic assessment of the true impact of MME's in the
      environment.

PMID- 21888873
TI  - Levels and patterns of hydroxylated polychlorinated biphenyls (OH-PCBs) and their
      associations with thyroid hormones in hooded seal (Cystophora cristata) mother
      pup pairs.
AB  - Blood (plasma/serum) samples from 14 adult female and their pups (1-4 days old)
      captured in the West Ice, east of Greenland were analysed for concentrations of
      total and free thyroxine and triiodothyronine (TT4, FT4, TT3, FT3), and
      hydroxylated polychlorinated biphenyls (OH-PCBs). The levels of all thyroid
      hormones (THs) were significantly higher in pups than in mothers. Sum OH-PCB
      levels (SigmaOH-PCBs: 4-OH-CB107, 3'-OH-CB138, 4-OH-CB146, 4'-OH-CB172, 4-OH
      CB187) were significantly higher in mothers (3.98 +/- 1.55 pmol/g; 1.40 +/- 0.54
      ng/g wet weight) as compared to pups (1.95 +/- 0.78 pmol/g; 0.68 +/- 0.28 ng/g
      wet weight). Plasma levels of TT4 and FT4 in mothers increased as a function of
      pup age, as did levels of individual OH-PCBs in both mothers and pups. The
      pattern of OH-PCBs in the pups was similar to their mothers. We suggest that OH
      PCBs found in pups are transferred from their mothers during gestation and that
      the transfer also continues after parturition via milk. Principal component
      analysis (PCA) showed that in pups, 4-OH-CB107 and 3'-OH-CB138 were negatively
      associated with FT4:FT3 and TT3:FT3 ratios, respectively. These relationships
      were confirmed by partial correlation analysis correcting for pup age. PCA
      suggested that 4'-OH-CB172 and 4-OH-CB187 were negatively associated with TT3 in
      mothers. However, this was not confirmed by correlation tests. Although
      statistical relationships should be interpreted with caution, the study indicates
      that young developing seals are more sensitive compared to adults with respect to
      TH-related effects of OH-PCBs.

PMID- 21888874
TI  - Inducible and repressable oncogene-addicted hepatocellular carcinoma in Tet-on
      xmrk transgenic zebrafish.
AB  - BACKGROUND & AIMS: Liver cancer, mainly hepatocellular carcinoma, is a major
      malignancy and currently there are no effective treatment protocols due to
      insufficient understanding of hepatocarcinogenesis. As a potentially high
      throughput and cost-effective experimental model, the zebrafish is increasingly
      recognized for disease studies. Here, we aim at using the zebrafish to generate a
      convenient hepatocellular carcinoma model. METHODS: Using the Tet-on system for
      liver-specific expression of fish oncogene xmrk, a hyperactive version of
      epidermal growth factor receptor homolog, we have generated transgenic zebrafish
      with inducible development of liver cancer. RESULTS: Liver tumors were rapidly
      induced with 100% penetrance in both juvenile and adult xmrk transgenic fish.
      Histological examination indicated that they all showed features of
      hepatocellular carcinoma. The induced liver tumors regressed rapidly upon inducer
      withdrawal. During the tumor induction stage, we detected increased cell
      proliferation and activation of Xmrk downstream targets Erk and Stat5, which were
      important for liver tumorigenesis as proved by inhibition experiments. When
      tumors regressed, there were decreased phosphorylated Erk and Stat5 accompanied
      with an increase in apoptosis. CONCLUSIONS: Our zebrafish model demonstrates the
      potential of a hyperactivated epidermal growth factor receptor pathway in
      initiating heptocarcinogenesis. It provides clear evidence for the requirement of
      only a single oncogene for HCC initiation and maintenance and is thus a
      convenient model for further investigation of oncogene addiction and future anti
      cancer drug screening.

PMID- 21888875
TI  - MicroRNA-135a contributes to the development of portal vein tumor thrombus by
      promoting metastasis in hepatocellular carcinoma.
AB  - BACKGROUND & AIMS: Portal vein tumor thrombus (PVTT) has previously been
      demonstrated to correlate with poor prognosis of hepatocellular carcinoma.
      Approximately 50-80% of HCC is accompanied by portal or hepatic vein invasion.
      The underlying mechanisms of PVTT development remain unclear. This study aimed to
      elucidate the role of miR-135a in PVTT tumorigenesis. METHODS: In the present
      study, we investigated the expression of microRNAs and mRNAs in PVTT tissues
      using advanced microRNA and cDNA microarray techniques. MicroRNA (miR)-135a was
      noted to be highly over-expressed in PVTT and the cell line CSQT-2 and was
      selected for further study. We characterized the function of miR-135a in vitro
      and in vivo. We also analyzed the clinical relevance of miR-135a in relation to
      the prognosis and survival of HCC patients with PVTT. RESULTS: Our analyses found
      that the miRNA and mRNA expression profiles of PVTT were distinct from the
      parenchyma tumor. Overexpression of miR-135a favors invasive and metastatic
      behavior in vitro. Furthermore, in a CSQT-2 orthotopic transplantation nude mouse
      model, blockade of miR-135a significantly reduced PVTT incidence. We also found
      that miR-135a was transcribed by forkhead box M1 (FOXM1), and metastasis
      suppressor 1 (MTSS1) was identified as the direct and functional target of miR
      135a. Additionally, the cohort analysis revealed the relevance of miR-135a with
      respect to the prognosis and survival of HCC patients with PVTT. CONCLUSIONS: Our
      data suggest an important role for miR-135a in promoting PVTT tumorigenesis and
      indicate the potential application of miR-135a in PVTT therapy.

PMID- 21888877
TI  - C reactive protein levels in non-alcoholic fatty liver disease.

PMID- 21888876
TI  - A functional genomic screen reveals novel host genes that mediate interferon
      alpha's effects against hepatitis C virus.
AB  - BACKGROUND & AIMS: The precise mechanisms by which IFN exerts its antiviral
      effect against HCV have not yet been elucidated. We sought to identify host genes
      that mediate the antiviral effect of IFN-alpha by conducting a whole-genome siRNA
      library screen. METHODS: High throughput screening was performed using an HCV
      genotype 1b replicon, pRep-Feo. Those pools with replicate robust Z scores >=2.0
      entered secondary validation in full-length OR6 replicon cells. Huh7.5.1 cells
      infected with JFH1 were then used to validate the rescue efficacy of selected
      genes for HCV replication under IFN-alpha treatment. RESULTS: We identified and
      confirmed 93 human genes involved in the IFN-alpha anti-HCV effect using a whole
      genome siRNA library. Gene ontology analysis revealed that mRNA processing (23
      genes, p=2.756e-22), translation initiation (nine genes, p=2.42e-6), and IFN
      signaling (five genes, p=1.00e-3) were the most enriched functional groups. Nine
      genes were components of U4/U6.U5 tri-snRNP. We confirmed that silencing squamous
      cell carcinoma antigen recognized by T cells (SART1), a specific factor of tri
      snRNP, abrogates IFN-alpha's suppressive effects against HCV in both replicon
      cells and JFH1 infectious cells. We further found that SART1 was not IFN-alpha
      inducible, and its anti-HCV effector in the JFH1 infectious model was through
      regulation of interferon stimulated genes (ISGs) with or without IFN-alpha.
      CONCLUSIONS: We identified 93 genes that mediate the anti-HCV effect of IFN-alpha
      through genome-wide siRNA screening; 23 and nine genes were involved in mRNA
      processing and translation initiation, respectively. These findings reveal an
      unexpected role for mRNA processing in generation of the antiviral state, and
      suggest a new avenue for therapeutic development in HCV.

PMID- 21888878
TI  - Coffee consumption and reduced self-reported side effects in HIV-HCV co-infected
      patients during PEG-IFN and ribavirin treatment: results from ANRS CO13 HEPAVIH.

PMID- 21888880
TI  - Aortobifemoral prosthesis penetrating into the duodenal lumen.

PMID- 21888881
TI  - Variceal bleeding in cirrhotic patients is associated with adrenal dysfunction:
      what is the evidence?

PMID- 21888882
TI  - Portal biliopathy: diagnosis by endosonography.

PMID- 21888883
TI  - The dynamic nature of fluid resuscitation in acute pancreatitis.

PMID- 21888884
TI  - Gastrointestinal bleeding caused by primary small bowel lymphoma in a patient who
      received a renal transplant.

PMID- 21888885
TI  - Contraction-excitation coupling?

PMID- 21888887
TI  - Prevalence of the alternative lengthening of telomeres telomere maintenance
      mechanism in human cancer subtypes.
AB  - Approximately 10% to 15% of human cancers lack detectable telomerase activity,
      and a subset of these maintain telomere lengths by the telomerase-independent
      telomere maintenance mechanism termed alternative lengthening of telomeres (ALT).
      The ALT phenotype, relatively common in subtypes of sarcomas and astrocytomas,
      has rarely been reported in epithelial malignancies. However, the prevalence of
      ALT has not been thoroughly assessed across all cancer types. We therefore
      comprehensively surveyed the ALT phenotype in a broad range of human cancers. In
      total, two independent sets comprising 6110 primary tumors from 94 different
      cancer subtypes, 541 benign neoplasms, and 264 normal tissue samples were
      assessed by combined telomere-specific fluorescence in situ hybridization and
      immunofluorescence labeling for PML protein. Overall, ALT was observed in 3.73%
      (228/6110) of all tumor specimens, but was not observed in benign neoplasms or
      normal tissues. This is the first report of ALT in carcinomas arising from the
      bladder, cervix, endometrium, esophagus, gallbladder, kidney, liver, and lung.
      Additionally, this is the first report of ALT in medulloblastomas,
      oligodendrogliomas, meningiomas, schwannomas, and pediatric glioblastoma
      multiformes. Previous studies have shown associations between ALT status and
      prognosis in some tumor types; thus, further studies are warranted to assess the
      potential prognostic significance and unique biology of ALT-positive tumors.
      These findings may have therapeutic consequences, because ALT-positive cancers
      are predicted to be resistant to anti-telomerase therapies.

PMID- 21888888
TI  - Quantitation of amyloid beta peptides Abeta(1-38), Abeta(1-40), and Abeta(1-42)
      in human cerebrospinal fluid by ultra-performance liquid chromatography-tandem
      mass spectrometry.
AB  - Critical events in Alzheimer's disease (AD) involve an imbalance between the
      production and clearance of amyloid beta (Abeta) peptides from the brain. Current
      methods for Abeta quantitation rely heavily on immuno-based techniques. However,
      these assays require highly specific antibodies and reagents that are time
      consuming and expensive to develop. Immuno-based assays are also characterized by
      poor dynamic ranges, cross-reactivity, matrix interferences, and dilution
      linearity problems. In particular, noncommercial immunoassays are especially
      subject to high intra- and interassay variability because they are not subject to
      more stringent manufacturing controls. Combinations of these factors make
      immunoassays more labor-intensive and often challenging to validate in support of
      clinical studies. Here we describe a mixed-mode solid-phase extraction method and
      an ultra-performance liquid chromatography tandem mass spectrometry (SPE UPLC
      MS/MS) assay for the simultaneous quantitation of Abeta(1-38), Abeta(1-40), and
      Abeta(1-42) from human cerebrospinal fluid (CSF). Negative ion versus positive
      ion species were compared using their corresponding multiple reaction monitoring
      (MRM) transitions, and negative ions were approximately 1.6-fold greater in
      intensity but lacked selectivity in matrix. The positive ion MRM assay was more
      than sufficient to quantify endogenous Abeta peptides. Abeta standards were
      prepared in artificial CSF containing 5% rat plasma, and quality control samples
      were prepared in three pooled CSF sources. Extraction efficiency was greater than
      80% for all three peptides, and the coefficient of variation during analysis was
      less than 15% for all species. Mean basal levels of Abeta species from three CSF
      pools were 1.64, 2.17, and 1.26 ng/ml for Abeta(1-38); 3.24, 3.63, and 2.55 ng/ml
      for Abeta(1-40); and 0.50, 0.63, and 0.46 ng/ml for Abeta(1-42).

PMID- 21888890
TI  - C-terminal de novo sequencing of peptides using oxazolone-based derivatization
      with bromine signature.
AB  - Due to almost identical chemical properties of C-terminal and side-chain
      carboxylic groups, selective C-terminal derivatization has been difficult.
      Although oxazolone-based C-terminal derivatization is the only selective C
      terminal modification available, it has not been used widely because of its low
      derivatization efficiency. In this paper, an improved oxazolone chemistry for
      incorporation of Br signature to C-terminus is reported. MS/MS analysis of the
      brominated peptides led to a series of y ions with Br signature, facilitating de
      novo C-terminal sequencing.

PMID- 21888889
TI  - An electrochemical sensor based on single-stranded DNA-poly(sulfosalicylic acid)
      composite film for simultaneous determination of adenine, guanine, and thymine.
AB  - Poly(sulfosalicylic acid) and single-stranded DNA composite (PSSA-ssDNA)-modified
      glassy carbon electrode (GCE) was prepared by electropolymerization and then
      successfully used to simultaneously determine adenine (A), guanine (G), and
      thymine (T). The characterization of electrochemically synthesized PSSA-ssDNA
      film was investigated by scanning electron microscopy (SEM) and electrochemical
      impedance spectroscopy (EIS). The modified electrode exhibited enhanced
      electrocatalytic behavior and good stability for the simultaneous determination
      of A, G, and T in 0.1M phosphate buffer solution (PBS, pH 7.0). Well-separated
      voltammetric peaks were obtained among A, G, and T presented in the analyte
      mixture. Under the optimal conditions, the peak currents for A, G, and T
      increased linearly with the increase of analyte mixture concentration in the
      ranges of 6.5*10(-8) to 1.1*10(-6), 6.5*10(-8) to 1.1*10(-6), and 4.1*10(-6) to
      2.7*10(-5)M, respectively. The detection limits (signal/noise=3) for A, G, and T
      were 2.2*10(-8), 2.2*10(-8), and 1.4*10(-6)M, respectively.

PMID- 21888891
TI  - Detecting multiple proteins by Western blotting using same-species primary
      antibodies, precomplexed serum, and hydrogen peroxide.
AB  - Western blot detection of multiple proteins is challenged by the need to use
      antibodies from the same species and the harsh stripping methods that can remove
      protein or reduce protein antigenicity. Quenching using 27% hydrogen peroxide was
      developed as an alternative to stripping to inhibit horseradish peroxidase used
      to detect secondary antibodies. To detect two epitopes with same-species primary
      antibodies, quenching was followed by incubation in a precomplexed mixture of
      primary and secondary antibodies for the second epitope plus serum from that
      species. Both methods will be valuable in specific detection of multiple proteins
      by Western blotting, and will save time, valuable samples, and reagents.

PMID- 21888892
TI  - Structural elements of the mitochondrial preprotein-conducting channel Tom40
      dissolved by bioinformatics and mass spectrometry.
AB  - Most mitochondrial proteins are imported into mitochondria from the cytosolic
      compartment. Proteins destined for the outer or inner membrane, the inter
      membrane space, or the matrix are recognized and translocated by the TOM
      machinery containing the specialized protein import channel Tom40. The latter is
      a protein with beta-barrel shape, which is suggested to have evolved from a porin
      type protein. To obtain structural insights in the absence of a crystal structure
      the membrane topology of Tom40 from Neurospora crassa was determined by limited
      proteolysis combined with mass spectrometry. The results were interpreted on the
      basis of a structural model that has been generated for NcTom40 by using the
      structure of mouse VDAC-1 as a template and amino acid sequence information of
      approximately 270 different Tom40 and approximately 480 VDAC amino acid sequences
      for refinement. The model largely explains the observed accessible cleavage sites
      and serves as a structural basis for the investigation of physicochemical
      properties of the ensemble of our Tom40 sequence data set. By this means we
      discovered two conserved polar slides in the pore interior. One is possibly
      involved in the positioning of a pore-inserted helix; the other one might be
      important for mitochondrial pre-sequence peptide binding as it is only present in
      Tom40 but not in VDAC proteins. The outer surface of the Tom40 barrel reveals two
      conserved amino acid clusters. They may be involved in binding other components
      of the TOM complex or bridging components of the TIM machinery of the
      mitochondrial inner membrane.

PMID- 21888893
TI  - Analysis of the human HP1 interactome reveals novel binding partners.
AB  - Heterochromatin protein 1 (HP1) has first been described in Drosophila as an
      essential component of constitutive heterochromatin required for stable
      epigenetic gene silencing. Less is known about the three mammalian HP1 isotypes
      CBX1, CBX3 and CBX5. Here, we applied a tandem affinity purification approach
      coupled with tandem mass spectrometry methodologies in order to identify
      interacting partners of the mammalian HP1 isotypes. Our analysis identified with
      high confidence about 30-40 proteins co-eluted with CBX1 and CBX3, and around 10
      with CBX5 including a number of novel HP1-binding partners. Our data also suggest
      that HP1 family members are mainly associated with a single partner or within
      small protein complexes composed of limited numbers of components. Finally, we
      showed that slight binding preferences might exist between HP1 family members.

PMID- 21888894
TI  - The sphingosine-1-phosphate derivative NHOBTD inhibits angiogenesis both in vitro
      and in vivo.
AB  - Sphingosine-1-phosphate (S1P) plays an important role in angiogenesis by
      stimulating DNA synthesis, chemotactic motility, and early blood vessel
      formation. Accordingly, the S1P signaling pathway is an attractive target for
      novel anti-angiogenic therapeutics. Here, we describe a small synthetic
      derivative of S1P that acts as an anti-angiogenic agent. We found that the S1P
      derivative NHOBTD [N-((2S,3R)-3-hydroxy-1-morpholino-4-(3-octylphenyl)butan-2
      yl)tetradecanamide] suppressed S1P-induced invasion and tube formation by human
      umbilical vein endothelial cells. NHOBTD also suppressed S1P signaling, as seen
      by destabilization of hypoxia inducible factor-1 alpha (HIF-1alpha) and secretion
      of VEGF, a transcriptional target of HIF-1alpha. Moreover, NHOBTD profoundly
      blocked endogenous neovascularization of the chick embryo chorioallantoic
      membrane, without rupturing any existing vessels. Together, these results
      demonstrate that NHOBTD is a new anti-angiogenic molecule that is capable of
      perturbing S1P signaling, and provides the basis for developing new anti
      angiogenic drugs.

PMID- 21888895
TI  - Cheating death at the dawn of life: developmental control of apoptotic repression
      in the preimplantation embryo.
AB  - During early development, the mammalian embryo is resistant to pro-apoptotic
      signals because of biochemical properties of the mitochondrion and nucleus.
      Mitochondria of the bovine two-cell embryo are resistant to depolarization
      because of low amounts of the proapoptotic protein BAX and high concentrations of
      the anti-apoptotic protein BCL2. As development proceeds, BAX content increases,
      BCL2 content declines, and mitochondria becomes capable of pore formation and
      depolarization in response to pro-apoptotic signals. The nucleus of the two-cell
      embryo is resistant to degradation by the DNase DFFB because epigenetic
      modifications, including DNA methylation and histone deacetylation, mask
      internucleosomal sites for DNA cleavage. Blastomere DNA becomes progressively
      less methylated during development so that DNA becomes accessible to cleavage by
      DFFB.

PMID- 21888896
TI  - Crystal structure of the Cys2His2-type zinc finger domain of human DPF2.
AB  - DPF2 is an evolutionary highly conserved member of the d4-protein family
      characterized by an N-terminal 2/3 domain, a C2H2-type zinc finger (ZF), and a C
      terminal tandem PHD zinc finger. DPF2 is identified as a transcription factor and
      may be related with some cancers in human. Here, we report the crystal structure
      of the C2H2-type zinc finger domain of human DPF2 with a canonical C2H2 fold,
      which contains two beta strands and one alpha helix. Several conserved residues,
      including Lys207, Lys216 and Arg217, constitute a positively charged surface in
      C2H2 domain, which implicates that it has the potential to bind DNA. The side
      chains of the residues Y209, C211, C214, K216, Y218, L224, H227 and H232 form the
      hydrophobic core of C2H2 domain, which indicates a potential-binding surface in
      the human DPF2.

PMID- 21888897
TI  - Kelch-like 20 up-regulates the expression of hypoxia-inducible factor-2alpha
      through hypoxia- and von Hippel-Lindau tumor suppressor protein-independent
      regulatory mechanisms.
AB  - Despite their structural similarity, hypoxia-inducible factor (HIF)-1alpha and
      HIF-2alpha have distinct functional properties and exhibit distinct
      spatiotemporal expression patterns, suggesting that the expressions of the two
      proteins are regulated by different mechanisms. To clarify the HIF-2alpha
      specific regulatory mechanism, we screened HIF-2alpha-associated proteins in a
      yeast two-hybrid system and identified kelch-like 20 (KLHL20). HIF-2alpha, but
      not HIF-1alpha, interacted with KLHL20. siRNA-mediated knockdown of KLHL20
      decreased HIF-2alpha protein, but not HIF-2alpha mRNA or HIF-1alpha protein.
      Depletion of KLHL20 decreased hypoxia-induced HIF activity, and consequently
      resulted in decreased expression levels of HIF-2alpha-responsive genes such as
      VEGF and CITED2. In contrast, overexpression of KLHL20 increased the expression
      levels and transcriptional activities of the O(2)-sensitive wild-type and O(2)
      insensitive mutant forms of HIF-2alpha. KLHL20 siRNA also inhibited HIF-2
      activity in von Hippel-Lindau tumor suppressor protein (pVHL)-deficient 786-O
      cells. These results indicate that KLHL20 is a novel player that regulates HIF
      2alpha protein expression through mechanisms independent of hypoxia and pVHL.

PMID- 21888898
TI  - Effect of heparin and alendronate coating on titanium surfaces on inhibition of
      osteoclast and enhancement of osteoblast function.
AB  - The failure of orthopedic and dental implants has been attributed mainly to
      loosening of the implant from host bone, which may be due to weak bonding of the
      implant material to bone tissue. Titanium (Ti) is used in the field of orthopedic
      and dental implants because of its excellent biocompatibility and outstanding
      mechanical properties. Therefore, in the field of materials science and tissue
      engineering, there has been extensive research to immobilize bioactive molecules
      on the surface of implant materials in order to provide the implants with
      improved adhesion to the host bone tissue. In this study, chemically active
      functional groups were introduced on the surface of Ti by a grafting reaction
      with heparin and then the Ti was functionalized by immobilizing alendronate onto
      the heparin-grafted surface. In the MC3T3-E1 cell osteogenic differentiation
      study, the alendronate-immobilized Ti substrates significantly enhanced alkaline
      phosphatase activity (ALP) and calcium content. Additionally, nuclear factor
      kappa B ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells was
      inhibited with the alendronate-immobilized Ti as confirmed by TRAP analysis. Real
      time PCR analysis showed that mRNA expressions of osteocalcin and osteopontin,
      which are markers for osteogenesis, were upregulated in MC3T3-E1 cells cultured
      on alendronate-immobilized Ti. The mRNA expressions of TRAP and Cathepsin K,
      markers for osteoclastogenesis, in RAW264.7 cells cultured on alendronate
      immobilized Ti were down-regulated. Our study suggests that alendronate
      immobilized Ti may be a bioactive implant with dual functions to enhance
      osteoblast differentiation and to inhibit osteoclast differentiation
      simultaneously.

PMID- 21888899
TI  - Regulation of phycoerythrin synthesis and cellular morphology in Fremyella
      diplosiphon green mutants.
AB  - Light-dependent modification of photosynthetic pigmentation and cellular growth
      responses is commonly associated with increased fitness in photosynthetic
      organisms, including cyanobacteria. Prior analyses of pigmentation mutants in the
      freshwater cyanobacterium Fremyelladiplosiphon has resulted in the observation
      that RcaE is a photosensor responsible for regulating organismal responses to
      changes in red light (RL) and green light (GL). RcaE regulates both pigmentation
      and cellular morphology, yet previous investigations and the analysis of
      additional pigmentation mutants here show that the signaling pathways regulating
      pigmentation and morphology appear to branch downstream of RcaE. We provide
      evidence that a DeltacpeR mutant has altered regulation of cellular morphology in
      addition to a known disruption in phycoerythrin synthesis. This marks the first
      description of the association of a regulator with the control of cellular
      morphology under both RL and GL in F.diplosiphon, apart from RcaE. In addition to
      providing a link between CpeR and the photoregulation of morphology in
      F.diplosiphon, the isolation of a DeltacpeR::IS66 mutant in the UTEX 481 strain
      represents both the first isolation of an IS66-based gene disruption and
      verification of the existence of an IS66-related element in F. diplosiphon.

PMID- 21888900
TI  - Anti-CENPI autoantibodies in scleroderma patients with features of autoimmune
      liver diseases.
AB  - BACKGROUND: Anticentromere autoantibodies have been reported to be associated
      with scleroderma and serve as a marker in different rheumatic diseases in humans.
      Major centromere autoantigens described so far include constitutive kinetochore
      proteins such as CENPA, CENPB, CENPC and CENPH and facultative proteins such as
      CENPE, CENPF and INCENP. We examined the inner kinetochore component CENPI as a
      new putative centromere autoantigen in scleroderma patients. METHODS: To test for
      the presence of CENPI centromere autoantibodies, 72 sera from patients with
      systemic lupus erythematosus and systemic sclerosis were assayed by
      immunofluorescence and further tested by immunoblots with an Nt-CENPI recombinant
      protein. RESULTS: 8 out of 31 (25.8%) patients diagnosed of scleroderma or
      Undifferentiated Connective Tissue Disease (UCTD) produced anti-CENPI
      autoantibodies. Epitopes were demonstrated to be located mainly but not
      exclusively in the N-terminal domain of the human CENPI protein. Five of the 8
      (62.5%) CENPI positive sera also had other autoantibodies related to primary
      biliary cirrhosis. Further, two patients (25%) with anti-CENPI autoantibodies had
      concurrent diagnosis of primary biliary cirrhosis. CONCLUSIONS: This study
      demonstrates that CENPI, a centromere protein that localizes to the inner
      kinetochore structure, is a human autoantigen. The significance of anti-CENPI
      autoantibodies could be relevant in scleroderma patients as a marker for
      concurrent autoimmune liver disease.

PMID- 21888901
TI  - Proguanylin and prouroguanylin--assay evaluation and clinical analyte
      characterization.
AB  - BACKGROUND: The biomarkers proguanylin and prouroguanylin are members of the
      natriuretic peptide family. The aim of this study was to evaluate two
      commercially available assays for proguanylin and prouroguanylin and to further
      characterize both analytes in terms of important clinical features. METHODS: We
      evaluated precision and linearity of the BioVendor human proguanylin and
      prouroguanylin ELISAs. In order to characterize both analytes, we tested in vitro
      analyte stabilities at -80  degrees C, and determined biological variability and
      reference values for proguanylin and prouroguanylin. RESULTS: Within-run and
      total coefficients of variation were <10% for the BioVendor proguanylin and
      prouroguanylin assays. Both methods were linear across the tested measurement
      ranges. The analytes proguanylin and prouroguanylin were stable for at least 2
      months at -80  degrees C. With respect to biological variability, the reference
      change values (RCV) were 27% and 59% for proguanylin and prouroguanylin,
      respectively. For proguanylin, age-independent reference values were 4.0-13.4
      ng/mL in males and 4.6-16.3 ng/mL in females. For prouroguanylin, age- and sex
      independent reference values were 2.1-11.2 ng/mL. CONCLUSION: The BioVendor human
      proguanylin ELISA and the BioVendor human prouroguanylin ELISA meet the needs of
      quality specifications of laboratory medicine. The results of the
      characterization of both analytes provide essential information for further
      clinical studies.

PMID- 21888902
TI  - Serum pigment epithelium-derived factor levels are increased in patients with
      biopsy-proven nonalcoholic fatty liver disease and independently associated with
      liver steatosis.
AB  - BACKGROUND: Increased serum concentrations of pigment epithelium-derived factor
      (PEDF) have been linked to the metabolic syndrome in the general population.
      However, the relationship between serum PEDF and nonalcoholic fatty liver disease
      (NAFLD), a hepatic manifestation of the metabolic syndrome, remains unknown.
      METHODS: We assayed serum PEDF levels in 156 patients with biopsy-proven NAFLD
      and 103 nonsteatotic control subjects who were matched for age and sex. The
      association between levels of PEDF and clinical, biochemical, and histological
      phenotypes was examined. RESULTS: NAFLD patients had significantly higher serum
      PEDF levels (1.97+/-0.50 MUg/mL) than control subjects (1.51+/-0.49 MUg/mL,
      Student's t test, P<0.001). Multivariable-adjusted stepwise regression analysis
      showed that PEDF ([beta]=0.32, t=3.13, P=0.002) and triglycerides ([beta]=0.22,
      t=2.23, P=0.02) were, in the order they entered into the model, the main
      independent predictors of steatosis scores in our patients with NAFLD.
      CONCLUSIONS: Serum PEDF levels are significantly increased in patients with
      biopsy-proven NAFLD and are associated with liver steatosis independently of
      traditional risk factors.

PMID- 21888903
TI  - Ngn3(+) endocrine progenitor cells control the fate and morphogenesis of
      pancreatic ductal epithelium.
AB  - During pancreas development, endocrine and exocrine cells arise from a common
      multipotent progenitor pool. How these cell fate decisions are coordinated with
      tissue morphogenesis is poorly understood. Here we have examined ductal
      morphology, endocrine progenitor cell fate and Notch signaling in Ngn3(-/-) mice,
      which do not produce islet cells. Ngn3 deficiency results in reduced branching
      and enlarged pancreatic duct-like structures, concomitant with Ngn3 promoter
      activation throughout the ductal epithelium and reduced Notch signaling.
      Conversely, forced generation of surplus endocrine progenitor cells causes
      reduced duct caliber and an excessive number of tip cells. Thus, endocrine
      progenitor cells normally provide a feedback signal to adjacent multipotent
      ductal progenitor cells that activates Notch signaling, inhibits further
      endocrine differentiation and promotes proper morphogenesis. These results
      uncover a novel layer of regulation coordinating pancreas morphogenesis and
      endocrine/exocrine differentiation, and suggest ways to enhance the yield of beta
      cells from stem cells.

PMID- 21888904
TI  - NO donor induces Nec-1-inhibitable, but RIP1-independent, necrotic cell death in
      pancreatic beta-cells.
AB  - Nitric oxide (NO) has been implicated in pancreatic beta-cell death in the
      development of diabetes. The mechanisms underlying NO-induced beta-cell death
      have not been clearly defined. Recently, receptor-interacting protein-1 (RIP1)
      dependent necrosis, which is inhibited by necrostatin-1, an inhibitor of RIP1,
      has emerged as a form of regulated necrosis. Here, we show that NO donor-induced
      beta-cell death was inhibited by necrostatin-1. Unexpectedly, however, RIP1
      knockdown neither inhibited cell death nor altered the protective effects of
      necrostatin-1 in NO donor-treated beta-cells. These results indicate that NO
      donor induces necrostatin-1-inhibitable necrotic beta-cell death independent of
      RIP1. Our findings raise the possibility that NO-mediated beta-cell necrosis may
      be a novel form of signal-regulated necrosis, which play a role in the
      progression of diabetes.

PMID- 21888905
TI  - Role of Sch9 in regulating Ras-cAMP signal pathway in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae PKA plays a major role in regulating cell growth,
      metabolism, and stress resistance. We report that Sch9 regulates PKA directly and
      SCH9 deletion enhances PKA activity by showing that: (1) Bcy1 predominately
      localized in the nucleus in glycerol-grown sch9Delta cells; (2) large part of the
      catalytic subunits of PKA transferred from the nucleus to the cytoplasm in
      sch9Delta cells; (3) higher protein stability of Tpk2 resulted in higher protein
      level of Tpk2 in sch9Delta than in wild type cells. Our investigations suggest
      that Sch9 regulates phosphorylation of Bcy1. We also observed hyper
      phosphorylation of Cdc25 in sch9Delta, in contrast to the tpk2Delta and
      tpk2Deltasch9Delta mutants, suggesting that feedback inhibition of PKA on Cdc25
      is through Tpk2.

PMID- 21888906
TI  - Evidence for beta-nicotinamide adenine dinucleotide as a purinergic, inhibitory
      neurotransmitter in doubt.

PMID- 21888907
TI  - Uncommon cause of an inflammatory pancreatic head tumor. Diagnosis: Purulent
      actinomycosis and incidental T1-carcinoid of the pancreatic head.

PMID- 21888908
TI  - Circulating salmon 28- and 22-kDa insulin-like growth factor binding proteins
      (IGFBPs) are co-orthologs of IGFBP-1.
AB  - Circulating insulin-like growth factor binding proteins (IGFBPs) play pivotal
      roles in stabilizing IGFs and regulating their availability to target tissues. In
      the teleost circulation, three major IGFBPs are typically detected by ligand
      blotting with molecular masses around 20-25, 28-32 and 40-45kDa. However, their
      identity is poorly established and often confused. We previously identified
      salmon 22- and 41-kDa forms as IGFBP-1 and -2b, respectively. In the present
      study, we cloned the cDNA of 28-kDa IGFBP from Chinook salmon (Oncorhynchus
      tshawytscha) as well as rainbow trout (Oncorhynchus mykiss) based on the partial
      N-terminal amino acid sequence of purified protein and identified it as an
      ortholog of IGFBP-1. Structural and phylogenetic analyses revealed that the 28
      kDa IGFBP is more closely related to human IGFBP-1 and zebrafish IGFBP-1a than
      the previously identified salmon IGFBP-1 (i.e. 22-kDa IGFBP). We thus named
      salmon 28- and 22-kDa forms as IGFBP-1a and -1b, respectively. Salmon IGFBP-1a
      contains a potential PEST region involved in rapid protein turnover and
      phosphorylation sites typically found in mammalian IGFBP-1, although the PEST and
      phosphorylation scores are not as high as those of human IGFBP-1. There was a
      striking difference in tissue distribution patterns between subtypes; Salmon
      igfbp-1a was expressed in a variety of tissues while igfbp-1b was almost
      exclusively expressed in the liver, suggesting that IGFBP-1a has more local
      actions. Direct seawater exposure (osmotic stress) of Chinook salmon parr caused
      increases in both IGFBP-1s in plasma, while IGFBP-1b appeared to be more
      sensitive. The presence of two co-orthologs of IGFBP-1 in the circulation in
      salmon, and most likely in other teleosts, provides a good opportunity to
      investigate subfunction partitioning of duplicated IGFBP-1 during postnatal
      growth.

PMID- 21888909
TI  - PDEs create local domains of cAMP signaling.
AB  - In the light of the knowledge accumulated over the years, it becomes clear that
      intracellular cAMP is not uniformly distributed within cardiomyocytes and that
      cAMP compartmentation is required for adequate processing and targeting of the
      information generated at the membrane. Localized cAMP signals may be generated by
      interplay between discrete production sites and restricted diffusion within the
      cytoplasm. In addition to specialized membrane structures that may limit cAMP
      spreading, degradation of the second messenger by cyclic nucleotide
      phosphodiesterases (PDEs) appears critical for the formation of dynamic
      microdomains that confer specificity of the response to various hormones. This
      review will cover the role of the different cAMP-PDE isoforms in this process.
      This article is part of a Special Issue entitled "Local Signaling in Myocytes."

PMID- 21888910
TI  - Calcium-calmodulin dependent protein kinase II (CaMKII): a main signal
      responsible for early reperfusion arrhythmias.
AB  - To explore whether CaMKII-dependent phosphorylation events mediate reperfusion
      arrhythmias, Langendorff perfused hearts were submitted to global
      ischemia/reperfusion. Epicardial monophasic or transmembrane action potentials
      and contractility were recorded. In rat hearts, reperfusion significantly
      increased the number of premature beats (PBs) relative to pre-ischemic values.
      This arrhythmic pattern was associated with a significant increase in CaMKII
      dependent phosphorylation of Ser2814 on Ca(2+)-release channels (RyR2) and Thr17
      on phospholamban (PLN) at the sarcoplasmic reticulum (SR). These phenomena could
      be prevented by the CaMKII-inhibitor KN-93. In transgenic mice with targeted
      inhibition of CaMKII at the SR membranes (SR-AIP), PBs were significantly
      decreased from 31+/-6 to 5+/-1 beats/3min with a virtually complete disappearance
      of early-afterdepolarizations (EADs). In mice with genetic mutation of the CaMKII
      phosphorylation site on RyR2 (RyR2-S2814A), PBs decreased by 51.0+/-14.7%. In
      contrast, the number of PBs upon reperfusion did not change in transgenic mice
      with ablation of both PLN phosphorylation sites (PLN-DM). The experiments in SR
      AIP mice, in which the CaMKII inhibitor peptide is anchored in the SR membrane
      but also inhibits CaMKII regulation of L-type Ca(2+) channels, indicated a
      critical role of CaMKII-dependent phosphorylation of SR proteins and/or L-type
      Ca(2+) channels in reperfusion arrhythmias. The experiments in RyR2-S2814A
      further indicate that up to 60% of PBs related to CaMKII are dependent on the
      phosphorylation of RyR2-Ser2814 site and could be ascribed to delayed
      afterdepolarizations (DADs). Moreover, phosphorylation of PLN-Thr17 and L-type
      Ca(2+) channels might contribute to reperfusion-induced PBs, by increasing SR
      Ca(2+) content and Ca(2+) influx.

PMID- 21888912
TI  - Identification of cardiovascular microRNA targetomes.
AB  - MicroRNAs (miRNAs) are strong post-transcriptional regulators targeting multiple
      targets. Endogenously transcribed, miRNAs specifically bind to complementary
      sequences of mRNAs and repress their expression thus govern control of cellular
      signaling pathways. An altered miRNA expression is causally related to
      cardiovascular disease. Identification of miRNA-dependent pathways is therefore
      an important aim to develop new therapeutic approaches. To understand miRNA
      function in various cardiovascular cells, the identification of individual miRNA
      target genes is of utmost importance. Indeed, the biological function of a miRNA
      is dependent on the availability of potential targets in a cell. We here
      summarize and discuss current challenging approaches to identify miRNA targetomes
      which will help to understand miRNA function in cardiac homeostasis and disease.

PMID- 21888911
TI  - Different subcellular populations of L-type Ca2+ channels exhibit unique
      regulation and functional roles in cardiomyocytes.
AB  - Influx of Ca(2+) through L-type Ca(2+) channels (LTCCs) contributes to numerous
      cellular processes in cardiomyocytes including excitation-contraction (EC)
      coupling, membrane excitability, and transcriptional regulation. Distinct
      subpopulations of LTCCs have been identified in cardiac myocytes, including those
      at dyadic junctions and within different plasma membrane microdomains such as
      lipid rafts and caveolae. These subpopulations of LTCCs exhibit regionally
      distinct functional properties and regulation, affording precise spatiotemporal
      modulation of L-type Ca(2+) current (I(Ca,L)). Different subcellular LTCC
      populations demonstrate variable rates of Ca(2+)-dependent inactivation and
      sometimes coupled gating of neighboring channels, which can lead to focal,
      persistent I(Ca,L). In addition, the assembly of spatially defined macromolecular
      signaling complexes permits compartmentalized regulation of I(Ca,L) by a variety
      of neurohormonal pathways. For example, beta-adrenergic receptor subtypes signal
      to different LTCC subpopulations, with beta(2)-adrenergic activation leading to
      enhanced I(Ca,L) through caveolar LTCCs and beta(1)-adrenergic stimulation
      modulating LTCCs outside of caveolae. Disruptions in the normal subcellular
      targeting of LTCCs and associated signaling proteins may contribute to the
      pathophysiology of a variety of cardiac diseases including heart failure and
      certain arrhythmias. Further identifying the characteristic functional properties
      and array of regulatory molecules associated with specific LTCC subpopulations
      will provide a mechanistic framework to understand how LTCCs contribute to
      diverse cellular processes in normal and diseased myocardium. This article is
      part of a Special Issue entitled "Local Signaling in Myocytes".

PMID- 21888915
TI  - Spectroscopy and a high-resolution crystal structure of Tyr263 mutants of
      cyanobacterial phytochrome Cph1.
AB  - Phytochromes are biliprotein photoreceptors that can be photoswitched between red
      light-absorbing state (Pr) and far-red-light-absorbing state (Pfr). Although
      three-dimensional structures of both states have been reported, the
      photoconversion and intramolecular signaling mechanisms are still unclear. Here,
      we report UV-Vis absorbance, fluorescence and CD spectroscopy along with various
      photochemical parameters of the wild type and Y263F, Y263H and Y263S mutants of
      the Cph1 photosensory module, as well as a 2.0-A-resolution crystal structure of
      the Y263F mutant in its Pr ground state. Although Y263 is conserved, we show that
      the aromatic character but not the hydroxyl group of Y263 is important for Pfr
      formation. The crystal structure of the Y263F mutant (Protein Data Bank ID: 3ZQ5)
      reaffirms the ZZZssa chromophore configuration and provides a detailed picture of
      its binding pocket, particularly conformational heterogeneity around the
      chromophore. Comparison with other phytochrome structures reveals differences in
      the relative position of the PHY (phytochrome specific) domain and the
      interaction of the tongue with the extreme N-terminus. Our data support the
      notion that native phytochromes in their Pr state are structurally heterogeneous.

PMID- 21888913
TI  - AMP-activated protein kinase connects cellular energy metabolism to KATP channel
      function.
AB  - AMPK is an important sensor of cellular energy levels. The aim of these studies
      was to investigate whether cardiac K(ATP) channels, which couple cellular energy
      metabolism to membrane excitability, are regulated by AMPK activity. We
      investigated effects of AMPK on rat ventricular K(ATP) channels using
      electrophysiological and biochemical approaches. Whole-cell K(ATP) channel
      current was activated by metabolic inhibition; this occurred more rapidly in the
      presence of AICAR (an AMPK activator). AICAR had no effects on K(ATP) channel
      activity recorded in the inside-out patch clamp configuration, but ZMP (the
      intracellular intermediate of AICAR) strongly activated K(ATP) channels. An AMPK
      mediated effect is demonstrated by the finding that ZMP had no effect on K(ATP)
      channels in the presence of Compound C (an AMPK inhibitor). Recombinant AMPK
      activated Kir6.2/SUR2A channels in a manner that was dependent on the AMP
      concentration, whereas heat-inactivated AMPK was without effect. Using mass
      spectrometry and co-immunoprecipitation approaches, we demonstrate that the AMPK
      alpha-subunit physically associates with K(ATP) channel subunits. Our data
      demonstrate that the cardiac K(ATP) channel function is directly regulated by
      AMPK activation. During metabolic stress, a small change in cellular AMP that
      activates AMPK can be a potential trigger for K(ATP) channel opening. This
      article is part of a Special Issue entitled "Local Signaling in Myocytes".

PMID- 21888914
TI  - Structural and thermodynamic comparison of the catalytic domain of AMSH and AMSH
      LP: nearly identical fold but different stability.
AB  - AMSH plays a critical role in the ESCRT (endosomal sorting complexes required for
      transport) machinery, which facilitates the down-regulation and degradation of
      cell-surface receptors. It displays a high level of specificity toward cleavage
      of Lys63-linked polyubiquitin chains, the structural basis of which has been
      understood recently through the crystal structure of a highly related, but ESCRT
      independent, protein AMSH-LP (AMSH-like protein). We have determined the X-ray
      structure of two constructs representing the catalytic domain of AMSH: AMSH244,
      the JAMM (JAB1/MPN/MOV34)-domain-containing polypeptide segment from residues 244
      to 424, and AMSH219(E280A), an active-site mutant, Glu280 to Ala, of the segment
      from 219 to 424. In addition to confirming the expected zinc coordination in the
      protein, the structures reveal that the catalytic domains of AMSH and AMSH-LP are
      nearly identical; however, guanidine-hydrochloride-induced unfolding studies show
      that the catalytic domain of AMSH is thermodynamically less stable than that of
      AMSH-LP, indicating that the former is perhaps structurally more plastic. Much to
      our surprise, in the AMSH219(E280A) structure, the catalytic zinc was still held
      in place, by the compensatory effect of an aspartate from a nearby loop moving
      into a position where it could coordinate with the zinc, once again suggesting
      the plasticity of AMSH. Additionally, a model of AMSH244 bound to Lys63-linked
      diubiquitin reveals a type of interface for the distal ubiquitin significantly
      different from that seen in AMSH-LP. Altogether, we believe that our data provide
      important insight into the structural difference between the two proteins that
      may translate into the difference in their biological function.

PMID- 21888916
TI  - Discovery of improved EGF agonists using a novel in vitro screening platform.
AB  - Directed evolution is a powerful strategy for protein engineering; however,
      evolution of pharmaceutical proteins has been limited by the reliance of current
      screens on binding interactions. Here, we present a method that identifies
      protein mutants with improved overall cellular efficacy, an objective not
      feasible with previous approaches. Mutated protein libraries were produced in
      soluble, active form by means of cell-free protein synthesis. The efficacy of
      each individual protein was determined at a uniform dosage with a high-throughput
      protein product assay followed by a cell-based functional assay without requiring
      protein purification. We validated our platform by first screening mock libraries
      of epidermal growth factor (EGF) for stimulation of cell proliferation. We then
      demonstrated its effectiveness by identifying EGF mutants with significantly
      enhanced mitogenic activity at low concentrations compared to that of wild-type
      EGF. This is the first report of EGF mutants with improved biological efficacy
      despite much previous effort. Our platform can be extended to engineer a broad
      range of proteins, offering a general method to evolve proteins for improved
      biological efficacy.

PMID- 21888917
TI  - Roles of carboxyl groups in the transmembrane insertion of peptides.
AB  - We have used pHLIP(r) [pH (low) insertion peptide] to study the roles of carboxyl
      groups in transmembrane (TM) peptide insertion. pHLIP binds to the surface of a
      lipid bilayer as a disordered peptide at neutral pH; when the pH is lowered, it
      inserts across the membrane to form a TM helix. Peptide insertion is reversed
      when the pH is raised above the characteristic pK(a) (6.0). A key event that
      facilitates membrane insertion is the protonation of aspartic acid (Asp) and/or
      glutamic acid (Glu) residues, since their negatively charged side chains hinder
      membrane insertion at neutral pH. In order to gain mechanistic understanding, we
      studied the membrane insertion and exit of a series of pHLIP variants where the
      four Asp residues were sequentially mutated to nonacidic residues, including
      histidine (His). Our results show that the presence of His residues does not
      prevent the pH-dependent peptide membrane insertion at ~pH 4 driven by the
      protonation of carboxyl groups at the inserting end of the peptide. A further pH
      drop leads to the protonation of His residues in the TM part of the peptide,
      which induces peptide exit from the bilayer. We also find that the number of
      ionizable residues that undergo a change in protonation during membrane insertion
      correlates with the pH-dependent insertion into the lipid bilayer and exit from
      the lipid bilayer, and that cooperativity increases with their number. We expect
      that our understanding will be used to improve the targeting of acidic diseased
      tissue by pHLIP.

PMID- 21888918
TI  - Redesign of the PAK1 autoinhibitory domain for enhanced stability and affinity in
      biosensor applications.
AB  - The inhibitory switch (IS) domain of p21-activated kinase 1 (PAK1) stabilizes
      full-length PAK1 in an inactive conformation by binding to the PAK1 kinase
      domain. Competitive binding of small guanosine triphosphatases to the IS domain
      disrupts the autoinhibitory interactions and exposes the IS domain binding site
      on the surface of the kinase domain. To build an affinity reagent that
      selectively binds the activated state of PAK1, we used molecular modeling to
      reengineer the isolated IS domain so that it was soluble and stable, did not bind
      to guanosine triphosphatases and bound more tightly to the PAK1 kinase domain.
      Three design strategies were tested: in the first and second cases, extension and
      redesign of the N-terminus were used to expand the hydrophobic core of the
      domain, and in the third case, the termini were redesigned to be adjacent in
      space so that the domain could be stabilized by insertion into a loop in a host
      cyan fluorescent protein (CFP). The best-performing design, called CFP-PAcKer,
      was based on the third strategy and bound the kinase domain of PAK1 with an
      affinity of 400 nM. CFP-PAcKer binds more tightly to a full-length variant of
      PAK1 that is stabilized in the "open" state (K(d)=3.3 MUM) than to full-length
      PAK1 in the "closed" state (undetectable affinity), and binding can be monitored
      with fluorescence by placing an environmentally sensitive fluorescence dye on CFP
      PAcKer adjacent to the binding site.

PMID- 21888920
TI  - Stochastic theory of protein synthesis and polysome: ribosome profile on a single
      mRNA transcript.
AB  - The process of polymerizing a protein by a ribosome, using a messenger RNA (mRNA)
      as the corresponding template, is called translation. Ribosome may be regarded as
      a molecular motor for which the mRNA template serves also as the track. Often
      several ribosomes may translate the same (mRNA) simultaneously. The ribosomes
      bound simultaneously to a single mRNA transcript are the members of a
      polyribosome (or, simply, polysome). Experimentally measured polysome profile
      gives the distribution of polysome sizes. Recently a breakthrough in determining
      the instantaneous positions of the ribosomes on a given mRNA track has been
      achieved and the technique is called ribosome profiling (Ingolia et al., 2009;
      Guo et al., 2010). Motivated by the success of these techniques, we have studied
      the spatio-temporal organization of ribosomes by extending a theoretical model
      that we have reported elsewhere (Sharma and Chowdhury, 2011). This extended
      version of our model incorporates not only (i) mechano-chemical cycle of
      individual ribomes, and (ii) their steric interactions, but also (iii) the
      effects of (a) kinetic proofreading, (b) translational infidelity, (c) ribosome
      recycling, and (d) sequence inhomogeneities. The theoretical framework developed
      here will serve in guiding further experiments and in analyzing the data to gain
      deep insight into various kinetic processes involved in translation.

PMID- 21888919
TI  - Overcoming hysteresis to attain reversible equilibrium folding for outer membrane
      phospholipase A in phospholipid bilayers.
AB  - The free energy of unfolding of a membrane protein from lipids into water
      (DeltaG(o)(w,l)) describes its equilibrium thermodynamic stability. Knowing this
      parameter gives insight into a membrane protein's sequence-structure-energy
      relationships. However, there are few measures of membrane protein stability
      because of the technical difficulties associated with unfolded and partially
      folded states. Here, we describe the experimental process that allowed us to
      measure the DeltaG(o)(w,l) of the outer membrane phospholipase A into large
      unilamellar vesicles (LUVs) of 1,2-dilauroyl-sn-glycero-3-phosphocholine. To
      arrive at this reversible folding condition, we screened a large number of
      experimental variables: temperature, incubation time, salt concentration, pH,
      lipid composition and liposome morphology. The principal challenge we encountered
      under most conditions was hysteresis between folding and unfolding titrations. A
      second factor that compromised reversible folding was the observation that a
      fraction of the protein population tended to aggregate. We found that hysteresis
      could be completely eliminated on a feasible timescale by conducting experiments
      at acidic pH, by the slow dilution of the protein in the initial titration setup
      and by utilizing a low concentration of a detergent as a temporary "holdase" to
      solubilize the protein upon its initial dilution into folding conditions. We
      confirmed that the detergent did not disrupt the LUVs using fluorescence emission
      of lipid-sensitive dyes and light scattering. The results of our parameter search
      should be generally useful for efforts to measure DeltaG(o)(w,l) for other
      membrane proteins.

PMID- 21888921
TI  - Population stochasticity, random determination of handedness, and the genetic
      basis of antisymmetry.
AB  - Conspicuous lateral asymmetries of organisms are classified into two major
      categories: antisymmetry (AS), characterized by almost equal frequencies of
      dextral and sinistral morphs, and directional asymmetry (DA), in which one morph
      dominates. I compared and characterized two types of genes, both with existing
      examples, in their roles in the evolutionary transitions between AS and DA for
      the first time. Handedness genes (HGs) determine the chirality in a strict sense,
      while randomization genes (RGs) randomize the chirality. A theory predicts that,
      in an AS population maintained by HGs under negative frequency-dependent
      selection, RGs harness fluctuation of the morph frequencies as their driving
      force and thus increase their frequency until half of the population flips the
      phenotype. These predictions were confirmed by simulations. Consequently, RGs
      mask the genetic effects of HGs, which provides a possible explanation for the
      apparent lack of a genetic basis for AS in empirical AS studies.

PMID- 21888922
TI  - Unusual feeding behavior in wild great apes, a window to understand origins of
      self-medication in humans: role of sociality and physiology on learning process.
AB  - Certain toxic plants are beneficial for health if small amounts are ingested
      infrequently and in a specific context of illness. Among our closest living
      relatives, chimpanzees are found to consume plants with pharmacological
      properties. Providing insight on the origins of human self-medication, this study
      investigates the role social systems and physiology (namely gut specialization)
      play on learning mechanisms involved in the consumption of unusual and
      potentially bioactive foods by two great ape species. We collected data from a
      community of 41-44 wild chimpanzees in Uganda (11 months, 2008), and a group of
      11-13 wild western gorillas in Central African Republic (10 months, 2008-2009).
      During feeding, we recorded food consumed, its availability, and social
      interactions (including observers watching conspecifics and the observers'
      subsequent activity). Unusual food consumption in chimpanzees was twice higher
      than in gorillas. Additionally chimpanzees relied more on social information with
      vertical knowledge transmission on unusual foods by continually acquiring
      information during their life through mostly observing the fittest (pre
      senescent) adults. In contrast, in gorillas observational learning primarily
      occurred between related immatures, showing instead the importance of horizontal
      knowledge transmission. As chimpanzees' guts are physiologically less specialized
      than gorillas (more capable of detoxifying harmful compounds), unusual-food
      consumption may be more risky for chimpanzees and linked to reasons other than
      nutrition (like self-medication). Our results show that differences in sociality
      and physiology between the two species may influence mechanisms that discriminate
      between plants for nutrition and plants with potential therapeutic dietary
      components. We conclude that self-medication may have appeared in our ancestors
      in association with high social tolerance and lack of herbivorous gut
      specialization.

PMID- 21888923
TI  - Adverse childhood experiences, allostasis, allostatic load, and age-related
      disease.
AB  - How do adverse childhood experiences get 'under the skin' and influence health
      outcomes through the life-course? Research reviewed here suggests that adverse
      childhood experiences are associated with changes in biological systems
      responsible for maintaining physiological stability through environmental
      changes, or allostasis. Children exposed to maltreatment showed smaller volume of
      the prefrontal cortex, greater activation of the HPA axis, and elevation in
      inflammation levels compared to non-maltreated children. Adults with a history of
      childhood maltreatment showed smaller volume of the prefrontal cortex and
      hippocampus, greater activation of the HPA axis, and elevation in inflammation
      levels compared to non-maltreated individuals. Despite the clear limitations in
      making longitudinal claims from cross-sectional studies, work so far suggests
      that adverse childhood experiences are associated with enduring changes in the
      nervous, endocrine, and immune systems. These changes are already observable in
      childhood years and remain apparent in adult life. Adverse childhood experiences
      induce significant biological changes in children (biological embedding),
      modifying the maturation and the operating balance of allostatic systems. Their
      chronic activation can lead to progressive wear and tear, or allostatic load and
      overload, and, thus, can exert long-term effects on biological aging and health.

PMID- 21888924
TI  - 19-Nor-2alpha-(3-hydroxypropyl)-1alpha,25-dihydroxyvitamin D3 (MART-10) is a
      potent cell growth regulator with enhanced chemotherapeutic potency in liver
      cancer cells.
AB  - The discovery that the active form of vitamin D, 1alpha,25-dihydroxyvitamin D
      [1alpha,25(OH)(2)D] can modulate cellular proliferation and differentiation of
      cancer cells has led to its potential application as a chemotherapeutic agent to
      treat a variety of cancers. However, the use of 1alpha,25(OH)(2)D is limited due
      to its lethal side effect of hypercalcemia upon systemic administration. To
      overcome this drawback, numerous analogs have been synthesized. In this report,
      we examined the anti-proliferative activity of a new analog, 19-nor-2alpha-(3
      hydroxypropyl)-1alpha,25(OH)(2)D(3) (MART-10), in HepG2 liver cancer cells, and
      studied the potential mechanisms mediating this action. We found that MART-10
      exhibited approximately 100-fold greater activity than 1alpha,25(OH)(2)D(3) in
      inhibiting HepG2 cell proliferation as determined by cell number counting method.
      MART-10 was also approximately 100-fold more potent than 1alpha,25(OH)(2)D(3) in
      the upregulation of p21 and p27, that in turn arrested HepG2 cells at the
      G(0)/G(1) phase to a greater extent. Given that no active caspase 3 was detected
      and treatment with 1alpha,25(OH)(2)D(3) or MART-10 did not further increase the
      fractions of apoptotic and necrosis cells over the controls, the growth
      inhibitory effect of 1alpha,25(OH)(2)D(3) and MART-10 on HepG2 cells may not
      involve apoptosis. Overall, our findings suggest that MART-10 is a good candidate
      as a novel therapeutic regimen against liver cancer. Further pre-clinical studies
      using animal models and the subsequent human clinical trials are warranted.

PMID- 21888925
TI  - The consequences of rare sexual reproduction by means of selfing in an otherwise
      clonally reproducing species.
AB  - Clonal reproduction of diploids leads to an increase in heterozygosity over time.
      A single round of selfing will then create new homozygotic genotypes. Given the
      same allele frequencies, heritable genetic variation is larger when there are
      more extreme, i.e. homozygotic genotypes. So after a long clonal expansion, one
      round of selfing increases heritable genetic variation, but any fully or
      partially recessive deleterious alleles simultaneously impose a fitness cost.
      Here we calculate that the cost of selfing in the yeast Saccharomyces is
      experienced only by a minority of zygotes. This allows a round of selfing to act
      as an evolutionary capacitor to unlock genetic variation previously found in a
      cryptic heterozygous form. We calculate the evolutionary consequences rather than
      the evolutionary causes of sex. We explore a range of parameter values describing
      sexual frequencies, focusing especially on the parameter values known for wild
      Saccharomyces. Our results are largely robust to many other parameter value
      choices, so long as meiosis is rare relative to the strength of selection on
      heterozygotes. Results may also be limited to organisms with a small number of
      genes. We therefore expect the same phenomenon in some other species with similar
      reproductive strategies.

PMID- 21888926
TI  - Causality in medicine: getting back to the Hill top.
AB  - Evidence from randomized controlled trials (RCTs) is almost universally regarded
      as setting the "gold standard" for medical evidence. Claims that RCTs carry
      special epistemic weight are often based on the notion that evidence from
      randomized studies, and only such evidence, can establish that any observed
      connection between treatment and outcome was caused by the treatment on trial.
      Any non-randomized trial, on the contrary, inevitably leaves open the possibility
      that there is some underlying connection independent of receiving the treatment
      between outcome and one or more differentiating characteristics between those in
      the experimental and control groups; and hence inevitably leaves open the
      possibility that treatment and an observed better outcome were "merely
      correlated" rather than directly causally connected. Here I scrutinize this
      argument and point towards a more tenable and more modest position by recalling
      some of the forgotten insights of the RCT pioneer, Austin Bradford Hill.

PMID- 21888927
TI  - Importance of physicians in Chlamydia trachomatis control.
AB  - INTRODUCTION: During 2002-2006, reported rates of Chlamydia (CT) increased 17.3%
      nationally, with 43.6% of guideline eligible females screened in 2006. Annual
      costs associated with CT exceed $1.88 billion. We sought to determine the
      importance of private medical doctors (PMDs) and hospitals as screening venues in
      Illinois, USA and if this varied by county Rural-Urban Continuum Code (RUCC).
      METHODS: A retrospective analysis of all CT cases reported in Illinois during
      2002-2006. Counties were stratified by RUCC and eighteen provider types were
      condensed into nine venues. Venue positivity rates were derived from laboratory
      data. RESULTS: PMDs and hospitals reported 247,725 CT cases (33.1% and 25.4%,
      respectively). Sample positivity rates were 6.2% and 6.1%, comparable to 5.7% for
      family planning clinics (FPC). Distribution of cases within these venues (and STD
      clinics) by RUCC was highly significant (p<0.001). DISCUSSION: Even though
      screening guideline compliance is low, PMDs identify the majority of cases in
      Illinois and are consistently important screening venues at all levels of
      urbanization. As PMDs (and/or hospitals) exist in every Illinois county, it may
      be more efficient to augment screening rates at these venues rather than create
      new venues of other types which may be cost-ineffective in rural or low
      prevalence areas.

PMID- 21888928
TI  - Fatal hemophagocytic syndrome in a patient with a previously well-controlled
      asymptomatic HIV infection after EBV reactivation.
AB  - We present a rare case of hemophagocytic lymphohistiocytosis (HLH) in a 70 year
      old male patient with previously well-controlled HIV infection. We could confirm
      HLH in different organs post mortem. Since the diagnosis of HLH was delayed, the
      patient died despite initiation of chemotherapy. As cause for HLH, an EBV
      reactivation could be confirmed. In HIV infection, HLH may be the first HIV
      manifestation, often triggered by an opportunistic infection or immune
      reconstitution syndrome, but it is uncommon in the state of a well-controlled or
      aviremic HIV infection.

PMID- 21888929
TI  - Sustained attention in mice: expanding the translational utility of the SAT by
      incorporating the Michigan Controlled Access Response Port (MICARP).
AB  - Advances in mouse genetic technology have spurred increasing interest in the
      development of cognitive tasks for mice. Here, we describe and discuss the
      modifications necessary to adapt a task for the assessment of sustained attention
      performance for use in mice, including for taxing the top-down control of such
      performance. The validity of the Sustained Attention Task (SAT), including the
      distractor version (dSAT), has previously been demonstrated in rats and humans.
      This task requires moveable or retractable operanda; insertion of operanda into
      the operant chambers cues animals to respond to a prior signal or non-signal
      event, reporting either a hit or a miss, or a correct rejection or false alarm,
      respectively. Retractable levers did not support sufficiently high and stable
      levels of performance in mice. Given the widespread use of static nose-poke
      devices for testing operant performance in mice, we therefore designed and
      fabricated a retractable nose-poke device. As this device extends into chambers,
      a hole for nose-poking is slowly opened and closed again as the device retracts
      (termed the "Michigan Controlled Access Response Port", MICARP). Results describe
      the effects of variation of signal duration and event rate, trial outcome and
      trial type probability, effects of mice deprivation levels, and the reliability
      of SAT and dSAT performance. Mice perform the SAT and dSAT at levels comparable
      to those observed in rats. This task will be of assistance in expanding the
      translational usefulness of the SAT and dSAT.

PMID- 21888930
TI  - Differential gene expression and immune localization of the orexin system in the
      major salivary glands of pigs.
AB  - The aim of the present work was to characterize the expression and cell type
      distribution of the orexinic system in the major swine salivary glands by RT-PCR
      and immunohistochemistry techniques. Tissue samples of the mandibular (MSG), sub
      lingual, and parotid glands were obtained from six pigs. Marked differences in
      the expression of the orexinergic system were observed among the salivary glands.
      Prepro-orexin (PPOX) mRNA abundance was approximately 15-fold higher (P<0.05) in
      MSG than in the others salivary glands. The expression level of OX1R mRNA did not
      differ among the salivary glands, while that for OX2R transcript was
      undetectable. The hypothalamus, used as positive control tissues, showed the
      highest expression level for each component of the orexinic system.
      Immunoreactivity (IR) for both orexins A and B (OXA and OXB), and cognate
      receptors (OX1R and OX2R) were identified only in the excretory striated ducts of
      the MSG while acinar cells were not immunoreactive. Both sub-lingual and parotid
      glands completely lacked IR for any component of the orexinergic system. In the
      MSG, parasympathetic neurons and axons of local salivary gland ganglia were IR to
      both OXA and OXB and also to their receptors.

PMID- 21888931
TI  - Cross talk between smooth muscle cells and monocytes/activated monocytes via
      CX3CL1/CX3CR1 axis augments expression of pro-atherogenic molecules.
AB  - OBJECTIVE: In atherosclerotic lesions, fractalkine (CX3CL1) and its receptor
      (CX3CR1) expressed by smooth muscle cells (SMC) and monocytes/macrophages,
      mediate the heterotypic anchorage and chemotaxis of these cells. We questioned
      whether, during the close interaction of monocytes with SMC, the CX3CL1/CX3CR1
      pair modulates the expression of pro-atherogenic molecules in these cells.
      METHODS AND RESULTS: SMC were co-cultured with monocytes or LPS-activated
      monocytes (18h) and then the cells were separated and individually investigated
      for the gene and protein expression of TNFalpha, IL-1beta, IL-6, CX3CR1 and
      metalloproteinases (MMP-2, MMP-9). We found that SMC-monocyte interaction
      induced, in each cell type, an increased mRNA and protein expression of TNFalpha,
      IL-1beta, IL-6, CX3CR1, MMP-2 and MMP-9. Blocking the binding of fractalkine to
      CX3CR1 (by pre-incubation of monocytes with anti-CX3CR1 or by CX3CR1 siRNA
      transfection) before cell co-culture decreased the production of TNFalpha, CX3CR1
      and MMP-9. Monocyte-SMC interaction induced the phosphorylation of p38MAPK and
      activation of AP-1 transcription factor. Silencing the p65 (NF-kB subunit)
      inhibited the IL-1beta and IL-6 and silencing c-jun inhibited the TNFalpha,
      CX3CR1 and MMP-9 induced by SMC-monocyte interaction. CONCLUSIONS: The cross-talk
      between SMC and monocytes augments the inflammatory response in both cell types
      as revealed by the increased expression of TNFalpha, IL-1beta, IL-6, CX3CR1 and
      MMPs. Up-regulation of TNFalpha, CX3CR1 and MMP-9 is further increased upon
      interaction of SMC with activated monocytes and is dependent on
      fractalkine/CXRCR1 pair. These data imply that the fractalkine/CX3RCR1 axis may
      represent a therapeutic target to impede the inflammatory process associated with
      atherosclerosis.

PMID- 21888932
TI  - The AAA ATPase spastin links microtubule severing to membrane modelling.
AB  - In 1999, mutations in the gene encoding the microtubule severing AAA ATPase
      spastin were identified as a major cause of a genetic neurodegenerative condition
      termed hereditary spastic paraplegia (HSP). This finding stimulated intense study
      of the spastin protein and over the last decade, a combination of cell
      biological, in vivo, in vitro and structural studies have provided important
      mechanistic insights into the cellular functions of the protein, as well as
      elucidating cell biological pathways that might be involved in axonal maintenance
      and degeneration. Roles for spastin have emerged in shaping the endoplasmic
      reticulum and the abscission stage of cytokinesis, in which spastin appears to
      couple membrane modelling to microtubule regulation by severing.

PMID- 21888933
TI  - Ultrasound and microbubble-assisted gene delivery in Achilles tendons: long
      lasting gene expression and restoration of fibromodulin KO phenotype.
AB  - The aim of this study is to deliver genes in Achilles tendons using ultrasound
      and microbubbles. The rationale is to combine ultrasound-assisted delivery and
      the stimulation of protein expression induced by US. We found that mice tendons
      injected with 10 MUg of plasmid encoding luciferase gene in the presence of 5*105
      BR14 microbubbles, exposed to US at 1 MHz, 200 kPa, 40% duty cycle for 10 min
      were efficiently transfected without toxicity. The rate of luciferase expression
      was 100-fold higher than that obtained when plasmid alone was injected.
      Remarkably, the luciferase transgene was stably expressed for up to 108 days. DNA
      extracted from these sonoporated tendons was efficient in transforming competent
      E. coli bacteria, indicating that persistent intact pDNA was responsible for this
      long lasting gene expression. We used this approach to restore expression of the
      fibromodulin gene in fibromodulin KO mice. A significant fibromodulin expression
      was detected by quantitative PCR one week post-injection. Interestingly,
      ultrastructural analysis of these tendons revealed that collagen fibrils diameter
      distribution and circularity were similar to that of wild type mice. Our results
      suggest that this gene delivery method is promising for clinical applications
      aimed at modulating healing or restoring a degenerative tendon while offering
      great promise for gene therapy due its safety compared to viral methods.

PMID- 21888935
TI  - Heart transplantation with donor-specific antibodies directed toward denatured
      HLA-A*02:01: a case report.
AB  - The development of solid-phase assays for antibody detection has aided in the
      frequent detection of human leukocyte antigen (HLA) antibodies in
      nonalloimmunized males. Some scientists have reported that these HLA antibodies
      are produced to pathogens or allergens and the reactivity with HLA coated beads
      is the result of cross-reactive epitopes. These antibodies may also be directed
      toward cryptic epitopes exposed on the denatured beads. In this report, we
      describe the case of a heart transplanted patient who exhibited anti-HLA-A*02:01
      donor-specific antibodies detected with a bead-based assay (Luminex) and
      undetected with the complement-dependent cytotoxicity (CDC) test. Posttransplant
      monitoring, carried out with CDC and with Luminex on sera from this patient
      collected at the 2nd, 4th, 8th, and 12th posttransplant weeks and at 1 year
      confirmed the presence of anti-HLA-A*02:01 in all serum samples. Additional tests
      carried out with denatured and intact HLA molecules using single antigen beads
      demonstrated that the antibody was directed toward a cryptic epitope. One year
      after transplantation the patient is doing well. No sign of antibody-mediated
      rejection was observed throughout the follow-up. A comprehensive evaluation of
      the anamnesis and of antibodies is critical to avoid needless exclusion of organ
      donors.

PMID- 21888934
TI  - Photoactivation switch from type II to type I reactions by electron-rich micelles
      for improved photodynamic therapy of cancer cells under hypoxia.
AB  - Photodynamic therapy (PDT) is an emerging clinical modality for the treatment of
      a variety of diseases. Most photosensitizers are hydrophobic and poorly soluble
      in water. Many new nanoplatforms have been successfully established to improve
      the delivery efficiency of PS drugs. However, few reported studies have
      investigated how the carrier microenvironment may affect the photophysical
      properties of photosensitizer (PS) drugs and subsequently, their biological
      efficacy in killing malignant cells. In this study, we describe the modulation of
      type I and II photoactivation processes of the photosensitizer, 5,10,15,20
      tetrakis(meso-hydroxyphenyl)porphyrin (mTHPP), by the micelle core environment.
      Electron-rich poly(2-(diisopropylamino)ethyl methacrylate) (PDPA) micelles
      increased photoactivations from type II to type I mechanisms, which significantly
      increased the generation of O(2)(-) through the electron transfer pathway over
      (1)O(2) production through energy transfer process. The PDPA micelles led to
      enhanced phototoxicity over the electron-deficient poly(D,L-lactide) control in
      multiple cancer cell lines under argon-saturated conditions. These data suggest
      that micelle carriers may not only improve the bioavailability of photosensitizer
      drugs, but also modulate photophysical properties for improved PDT efficacy.

PMID- 21888936
TI  - Two meanings of reverse vaccinology and the empirical nature of vaccine science.

PMID- 21888937
TI  - A novel high-throughput neutralization assay for supporting clinical evaluations
      of human cytomegalovirus vaccines.
AB  - Neutralizing antibodies are considered an important component of protective
      immunity against congenital infection of human cytomegalovirus (HCMV), a
      frequently cited cause of birth defects. An effective HCMV vaccine is desired to
      induce potent neutralizing antibodies in seronegative females, so that the viral
      transmission to fetus would be blocked if the women contracted HCMV infections
      during their pregnancies. We describe a novel microneutralization assay to
      measure antiviral activities against HCMV in serum samples. The assay is based on
      detection of a dominant HCMV antigen expressed in cells, using near infrared dye
      labeled immune reagents. Since the detection is independent of viral cytopathic
      effects, this assay format has the appeal of a short turn-around time and a read
      out that is not subject to operator experience and judgment, making it a
      promising platform to support large scale clinical studies. In a serological
      survey of a cohort of 200 healthy females, we showed that the neutralizing titers
      measured in this assay are highly comparable to those from a neutralization assay
      based on an enzyme-linked immunostaining method. Lastly, to demonstrate the
      utility of this assay to support HCMV vaccine study, we presented the results of
      neutralizing titers from a rhesus macaque vaccination study.

PMID- 21888938
TI  - A novel alphavirus replicon-vectored vaccine delivered by adenovirus induces
      sterile immunity against classical swine fever.
AB  - Low efficacy of gene-based vaccines due to inefficient gene delivery and
      expression has been major bottleneck of their applications. Efforts have been
      made to improve the efficacy, such as gene gun and electroporation, but the
      strategies are difficult to put into practical use. In this study, we developed
      and evaluated an adenovirus-delivered, alphavirus replicon-vectored vaccine
      (chimeric vector-based vaccine) expressing the E2 gene of classical swine fever
      virus (CSFV) (rAdV-SFV-E2). Rabbits immunized with rAdV-SFV-E2 developed CSFV
      specific antibodies as early as 9 days and as long as 189 days and completely
      protected from challenge with C-strain. Pigs immunized with rAdV-SFV-E2 (n=5)
      developed robust humoral and cell-mediated responses to CSFV and were completely
      protected from subsequent lethal CSFV infection clinically and virologically. The
      level of immunity and protection induced by rAdV-SFV-E2 was comparable to that
      provided by the currently used live attenuated vaccine, C-strain. In contrast,
      both the conventional alphavirus replicon-vectored vaccine pSFV1CS-E2 and
      conventional adenovirus-vectored vaccine rAdV-E2 provided incomplete protection.
      The chimeric vector-based vaccine represents the first gene-based vaccine that is
      able to confer sterile immunity and complete protection against CSFV. The new
      concept vaccination strategy may also be valuable in vaccine development against
      other pathogens.

PMID- 21888939
TI  - Behavioral change with influenza vaccination: factors influencing increased
      uptake of the pandemic H1N1 versus seasonal influenza vaccine in health care
      personnel.
AB  - BACKGROUND: Many health care personnel (HCP) choose not to get vaccinated against
      influenza despite recommendations to do so. The pH1N1 epidemic gave a unique
      opportunity to evaluate the attitudes to influenza vaccination of a group of HCP
      who routinely choose not to get vaccinated, but accepted the pH1N1 vaccine.
      METHODS: HCP employed at a tertiary care hospital in Winnipeg, Canada who
      received the pH1N1 vaccine were invited to participate in an online survey asking
      about attitudes and experiences regarding seasonal and pH1N1 influenza and
      vaccination. Those eligible included primarily nurses, other clinical staff, and
      support staff, as few physicians work as employees. RESULTS: Of the 684
      respondents (29% return rate), 504 reported routinely getting vaccinated (RV) for
      seasonal influenza and 180 reported routinely not getting vaccinated (NRV). These
      two groups had different attitude towards the two strains of influenza, with
      markedly lower level of concern about seasonal influenza than pH1N1 for the NRV
      group. The contrast was especially notable regarding the NRV's view of the
      seriousness of the illness, their sense of exposure risk, and their confidence in
      the vaccine effectiveness (for all, seasonal<pH1N1, p<0.001). The most common
      motivators for getting vaccinated for both NRV and RV groups related to concerns
      about personal or family safety, while the choice to decline seasonal vaccination
      related primarily to lack concern about the illness and concerns about vaccine
      effectiveness and safety. Coworkers were influential in the decision to get the
      pH1N1 vaccine for the NRV group. CONCLUSION: For HCP who do not routinely get the
      seasonal vaccination, perception of risk outweighing side effect concerns
      appeared to be a major influence in going ahead with the pH1N1 vaccine.
      Educational campaigns that focus on personal benefit, engage peer champions, and
      address concerns about the vaccine may improve influenza vaccine uptake among
      health care personnel.

PMID- 21888940
TI  - Early immune responses in Atlantic salmon (Salmo salar L.) after immunization
      with PLGA nanoparticles loaded with a model antigen and beta-glucan.
AB  - Polymeric nanoparticles (NPs) of poly (lactic-co-glycolic) acid (PLGA) possess
      adjuvant properties. To date, there are few studies exploring their application
      as antigen carriers for vaccination of fish. This study presents a preclinical
      assessment of the early innate and adaptive immune responses in Atlantic salmon
      following immunization with PLGA NPs. A model antigen (TNP-LPH) and an
      immunostimulant (beta-glucan) were entrapped in NPs of 300-400nm either alone or
      in combination. Both the antigen and the beta-glucan were efficiently entrapped
      (>50%) in particles and an antigen release study indicated particle stability up
      to 50 days at 8 degrees C. Spleen and head kidney were analyzed for pro
      inflammatory markers (TNF-alpha, IL-1beta, IL-8, C3a) and T cell cytokines,
      effector molecules and transcription factors (IFN-gamma, T-bet, GATA-3, granzyme
      A, IL-10, Foxp3) at mRNA transcription levels 2, 4 and 8 days post i.p.
      immunization. NPs alone were able to moderately up-regulate pro-inflammatory
      immune responses. Addition of immunogenic cargo, either an antigen or beta-glucan
      generally increased the gene expression of pro-inflammatory markers, while
      administering both resulted in the highest gene expression. These findings were
      also reflected by concurrently increased levels of IL-10. Comparing the treatment
      groups injected with antigen and beta-glucan co-administered either in NPs or FCA
      demonstrated that the magnitude of the acute pro-inflammatory responses was equal
      between the treatments or highest in the NP injected group. Although elevated
      expression of granzyme A in the NP injected groups (carrying antigen and/or beta
      glucan) was observed, PLGA NPs were unable to induce T cell differentiation on
      mRNA gene expression levels, as increased levels of the indicating cytokines and
      transcriptions factors failed to occur. In conclusion, this study demonstrates
      that PLGA NPs have potential as an adjuvant in salmon vaccines as they enhance
      the early pro-inflammatory responses to immunization.

PMID- 21888941
TI  - The anti-oxidant and anti-apoptotic effects of nebivolol and zofenopril in a
      model of cerebral ischemia/reperfusion in rats.
AB  - The aim of this experiment was to investigate whether nebivolol and zofenopril
      have protective effects against oxidative damage and apoptosis induced by
      cerebral ischemia/reperfusion (I/R). There were seven groups of rats, with each
      containing eight rats. The groups were: the control group, I/R group, I/R plus
      zofenopril, I/R plus nebivolol, I/R plus nebivolol and zofenopril, zofenopril
      only and nebivolol only. Cerebral I/R was induced by clamping the bilateral
      common carotid artery and through hypotension. The rats were sacrificed 1h after
      ischemia, and histopathological and biochemical analyses were carried out on
      their brains. The total antioxidant capacity was evaluated by using an automated
      and colorimetric measurement method developed by Erel. I/R produced a significant
      increase in the levels of total oxidant status and malondialdehyde levels, the
      number of caspase-3 immunopositive cells and activities of prolidase and
      paraoxonase in brain when compared with the control group (p<0.05). A significant
      decrease in brain total antioxidant capacity and nitric oxide levels were found
      in I/R group when compared with the control group (p<0.05). Both nebivolol and
      zofenopril treatment prevented decreasing of the total antioxidant capacity and
      nitric oxide levels, produced by I/R in the brain (p<0.05). Both nebivolol and
      zofenopril treatment prevented the total oxidant status, malondialdehyde levels,
      activities of paraoxonase and prolidase from increasing in brains of rats exposed
      to I/R (p<0.05). In conclusion, both nebivolol and zofenopril protected rats from
      ischemia-induced brain injury. The protection may be due to the indirect
      prevention of oxidative stress and apoptosis.

PMID- 21888942
TI  - No genetic association between SLC7A10 and Japanese patients with schizophrenia.
AB  - Disrupted glutamatergic neurotransmission may be a pathophysiological feature in
      the brains from patients with schizophrenia, and glutamatergic amino acids
      including D-serine have been found to be involved in pathophysiology. Endogenous
      and exogenous D-serine have shown potential as biological markers for the
      pathophysiology of schizophrenia and especially as a therapeutic strategy in
      treatment-resistant schizophrenia (TRS). This is the first study investigating
      whether SLC7A10, a d-serine transporter gene, is associated with schizophrenia in
      Japanese patients. We investigated the association between schizophrenia in
      Japanese patients with SLC7A10 using six tag single nucleotide polymorphisms
      (SNPs). Results failed to show any association between Japanese schizophrenia and
      each individual SNP or with two-, three-, or four-window haplotype analyses. We
      also investigated whether SLC7A10 contributes to TRS in Japanese participants.
      Results showed no association. In conclusion, SLC7A10 had no apparent degree of
      association with schizophrenia as a candidate susceptibility gene in the disease
      per se.

PMID- 21888943
TI  - The altered cortical connectivity during spatial search for facial expressions in
      major depressive disorder.
AB  - To characterize the altered directed connectivity within a distributed cortical
      network, as is associated with the impaired attention modulation involved in the
      manifestation of mood disorder in depression, short-window partial directed
      coherence (PDC) combining with the event-related brain potentials (ERPs) was
      applied in this study. ERPs were recorded from 13 normal subjects and 12
      depressed patients during visual search for facial expressions. The evoked N2
      component of ERPs by responding to all neutral faces (F(1,22)=5.51, P<0.05) and
      the positive face was reduced in the depressed patients as compared to the normal
      subjects (F(1,22)=5.71, P<0.05), while the evoked N2 component by detecting the
      negative face showed no significant between-group effect (F(1,22)=2.10, P=0.16).
      The reduced N2 amplitude reflected deficits in effortful attentional modulation
      in depression. Obtained PDC values within the N2 time-window (150-300 ms post
      stimulus) showed weaker intra-frontal and intra-central directed interactions and
      enhanced occipital information output when responding to all neutral faces in
      depression relative to those in the normal group. Few decreased intra-frontal
      directed interactions were observed when detecting the emotional face in
      depression. The altered cortical directed connectivity contributed to the
      impairment occurring in the effortful attention modulation in depression. Our
      findings supported that the impaired attention modulation processing in
      depression was associated with the altered cortical connectivity.

PMID- 21888944
TI  - Structural analysis of nuclear receptors: from isolated domains to integral
      proteins.
AB  - Nuclear receptors (NRs) are ligand dependent transcription factors that regulate
      gene expression. A number of in depth structure-function relationship studies
      have been performed, in particular with drug design perspectives. Recent
      structural results concerning integral receptors in diverse functional states,
      obtained using a combination of different methods, now allow a better
      understanding of the mechanisms involved in molecular regulation. The structural
      data highlight the importance of DNA sequences for binding selectivity and the
      role of promoter response elements in the spatial organization of the protein
      domains into functional complexes. The solution structures of several heterodimer
      complexes reveal how the DNA directs the positioning of coactivators. In the case
      of PPARgamma-RXRalpha the comparison with the crystal structure reveals two
      different conformational states that illustrate the flexibility of the receptors.
      The results shed light on the dynamics of the molecular recognition process.

PMID- 21888945
TI  - Peroxisome proliferator-activated receptor activity is involved in the
      osteoblastic differentiation regulated by bone morphogenetic proteins and tumor
      necrosis factor-alpha.
AB  - Recent studies have suggested possible adverse effects of thiazolidinediones on
      bone metabolism. However, the detailed mechanism by which the activity of PPAR
      affects bone formation has not been elucidated. Impaired osteoblastic function
      due to cytokines is critical for the progression of inflammatory bone diseases.
      In the present study, we investigated the cellular mechanism by which PPAR
      actions interact with osteoblast differentiation regulated by BMP and TNF-alpha
      using mouse myoblastic C2C12 cells. BMP-2 and -4 potently induced the expression
      of various bone differentiation markers including Runx2, osteocalcin, type-1
      collagen and alkaline phosphatase (ALP) in C2C12 cells. When administered in
      combination with a PPARalpha agonist (fenofibric acid) but not with a PPARgamma
      agonist (pioglitazone), BMP-4 enhanced osteoblast differentiation through the
      activity of PPARalpha. The osteoblastic changes induced by BMP-4 were readily
      suppressed by treatment with TNF-alpha. Interestingly, the activities of
      PPARalpha and PPARgamma agonists reversed the suppression by TNF-alpha of
      osteoblast differentiation induced by BMP-4. Furthermore, TNF-alpha-induced
      phosphorylation of MAPKs, NFkappaB, IkappaB and Stat pathways was inhibited in
      the presence of PPARalpha and PPARgamma agonists with reducing TNF-alpha receptor
      expression. In view of the finding that inhibition of SAPK/JNK, Stat and NFkappaB
      pathways reversed the TNF-alpha suppression of osteoblast differentiation, we
      conclude that these cascades are functionally involved in the actions of PPARs
      that antagonize TNF-alpha-induced suppression of osteoblast differentiation. It
      was further discovered that the PPARalpha agonist enhanced BMP-4-induced
      Smad1/5/8 signaling through downregulation of inhibitory Smad6/7 expression,
      whereas the PPARgamma agonist impaired this activity by suppressing BMPRII
      expression. On the other hand, BMPs increased the expression levels of PPARalpha
      and PPARgamma in the process of osteoblast differentiation. Thus, PPARalpha
      actions promote BMP-induced osteoblast differentiation, while both activities of
      PPARalpha and PPARgamma suppress TNF-alpha actions. Collectively, our present
      data establishes that PPAR activities are functionally involved in modulating the
      interaction between the BMP system and TNF-alpha receptor signaling that is
      crucial for bone metabolism.

PMID- 21888946
TI  - Low barometric pressure aggravates neuropathic pain in guinea pigs.
AB  - Several clinical studies have demonstrated a consistent relationship between
      changes in meteorological factors, particularly barometric pressure, and pain
      intensity in subjects with chronic pain. We have previously demonstrated that
      exposure to artificially low barometric pressure (LP) intensifies pain-related
      behaviors in rats with neuropathic pain. In the present study, guinea pigs with
      unilateral L5 spinal nerve ligation (SNL) were placed in a pressure-controlled
      chamber and subjected to LP of 10 or 27hPa below the ambient pressure. The SNL
      surgery led to increased hindpaw withdrawal frequencies to 34-, 59-, and 239-mN
      von Frey filaments (VFFs). When the SNL animals were subjected to both LP
      exposures consecutively, the hindpaw withdrawal frequencies further increased;
      the effect was most significant when the animals were exposed to LP 27hPa below
      ambient pressure. In contrast, no change was seen in a group of sham-operated
      control animals. These results indicate that fluctuations in LP within the range
      of natural weather patterns can potentiate neuropathic pain in guinea pigs.

PMID- 21888947
TI  - An event-related potential study on cross-modal conversion of Chinese characters.
AB  - In the current study, we explored the effects of ERPs (event-related potentials),
      related to the cross-modal transfer from visual input to phonological retrieval.
      Using Chinese single-character words, participants were asked to make
      orthographic (intra-modal) and phonological (cross-modal) responses to visually
      presented words. By comparing the cross-modal and intra-modal tasks, we found
      that both tasks evoke similar activity in the early stage of lexical processing,
      showing the same pattern of N2 effect (a negative component peaking around 220
      ms) and P2 effect (a positive component peaking around 270 ms). However, the
      effect of the task was significant in the 300-700 ms time window, consisting of a
      frontal-based N400 effect and a parietal based late positive component (LPC)
      effect. These findings suggest that the frontal-based N400 is associated with
      orthography-to-phonology mapping in Chinese, and the LPC reflects greater
      requirement of maintaining retrieved information in working memory for the cross
      modal processing.

PMID- 21888948
TI  - Neurocognitive effects of first- and second-generation antipsychotic drugs in
      early-stage schizophrenia: a naturalistic 12-month follow-up study.
AB  - The study aimed to assess the cognitive effects of first- and second-generation
      antipsychotics on neurocognition under naturalistic treatment conditions. In a 12
      month, open-label, multicenter study, 698 patients with early-stage schizophrenia
      (duration of illness <=5 years) were prescribed chlorpromazine, sulpiride,
      clozapine, risperidone, olanzapine, quetiapine, or aripiprazole monotherapy. A
      neuropsychological battery including tests of attention, processing speed,
      learning/memory, and executive functioning was administered at baseline, 6- and
      12-months. The primary outcome was change in a cognitive composite score after 12
      months of treatment. At 12 months, treatment resulted in mild to moderate
      neurocognitive improvements of z=0.32 for chlorpromazine, 0.33 for sulpiride,
      0.43 for clozapine, 0.51 for risperidone, 0.69 for olanzapine, 0.64 for
      quetiapine and 0.46 for aripiprazole. However, the olanzapine and quetiapine
      groups demonstrated greater improvement in the composite score and processing
      speed than did the chlorpromazine and sulpiride groups. Both first- and second
      generation antipsychotics may improve cognitive function in patients with early
      stage schizophrenia. Given that some neurocognitive improvement is attributable
      to a practice effect, any improvement is likely to be in the range of a small
      effect size.

PMID- 21888949
TI  - Cocaine must enter the brain to evoke unconditioned dopamine release within the
      nucleus accumbens shell.
AB  - In addition to blocking dopamine (DA) uptake, cocaine also causes an
      unconditioned increase in DA release. In drug naive rats, this effect is most
      robust within the nucleus accumbens (NAc) shell. Recent studies have shown that,
      in rats trained to self-administer cocaine, cocaine may act in the periphery to
      enhance mesolimbic DA release. Further, these studies have suggested that
      peripheral cocaine action may also enhance unconditioned DA release. Here, we
      test if it is necessary for cocaine to enter the brain to evoke unconditioned
      increases in DA release within the NAc shell. Administration of a cocaine
      analogue that crosses the blood brain barrier (cocaine HCl) enhances electrically
      evoked DA release and the number of cocaine-evoked phasic DA release events
      (i.e., DA transients) within the NAc shell. However, administration of a cocaine
      analogue that does not cross the blood brain barrier (cocaine MI) does not alter
      either measure. We therefore conclude that cocaine must act within the central
      nervous system to evoke unconditioned DA release within the NAc shell.

PMID- 21888950
TI  - Chronic progesterone treatment of male rats with unilateral 6-hydroxydopamine
      lesion of the dorsal striatum exacerbates [corrected] parkinsonian symptoms.
AB  - Progesterone (PROG) shows neuroprotective effects in numerous lesion models,
      including a mouse model of Parkinson's disease (PD) induced by 1-methyl-4-phenyl
      1,2,3,6-tetrahydropyridine (MPTP). However, the possible beneficial effects of
      PROG on the behavioral and neurochemical impairments incurred in the
      hemiparkinsonian 6-hydroxydopamine (6-OHDA) model have not been investigated.
      Vehicle or PROG (4 mg/kg or 8 mg/kg) was daily applied over 13 days after
      unilateral injection of 6-OHDA into the dorsal striatum of male rats. Turning
      behavior, foot slips on a horizontal grid, and forelimb use during rearing in a
      cylinder were observed on days 4, 5, 9, 10, 13, and 14 postlesion, and then the
      brain samples were analyzed by HPLC-EC. Chronic 8 mg/kg of PROG administration
      increased the DOPAC/dopamine (DA) ratio in the lesioned striatum, ipsiversive
      turnings, and the number of hind limb slips and decreased the symmetrical use of
      forelimbs. Thus, contrary to hypothesis, the chronic treatment with PROG
      exasperated rather than alleviated the motor impairments in the hemiparkinsonian
      rats. Because previous studies with the MPTP model had shown protective effects
      when PROG treatment was administrated before the lesion, our results do not rule
      out such potential neuroprotective action with prelesion PROG treatment. However,
      our results raise the question of possible negative interactions between PROG and
      parkinsonian symptoms in males.

PMID- 21888952
TI  - Adolf Hopf's 1954 myeloarchitectonic parcellation of the human temporal lobe: a
      review and assessment.
AB  - In this review, Adolph Hopf's [21] myeloarchitectonic parcellation of the left
      hemisphere human temporal lobe is examined in light of current functional
      (neuroimaging) data, and by comparison with classical and recently published
      partial parcellations of the macaque temporal lobe. In order to effect these
      comparisons, the components of Hopf's parcellation were mapped to the human
      cortical PALS atlas using the Caret software, as were components of more recent
      partial temporal lobe parcellations. Correspondences between functionally defined
      structures, including the occipital and fusiform face areas and the
      parahippocampal place area, with components of the Hopf parcellation were
      determined by plotting the locations of activation foci published in neuroimaging
      studies of face and scene recognition studies on the PALS atlas, and comparing
      the location and extent of foci clusters with the topography of Hopf's
      myeloarchitectonic areas. In addition, potential homologies between macaque
      temporal lobe structures and Hopf's areas were established by mapping the
      component areas of macaque temporal cortex to the Caret software F99 macaque
      atlas, and comparing the topography of this mapping with the corresponding
      topography of the Hopf parcellation in the PALS atlas mapping. Relative expansion
      and contraction of temporal lobe structures over phylogeny are discussed in light
      of these potential homologies.

PMID- 21888951
TI  - Exogenous growth hormone attenuates cognitive deficits induced by intermittent
      hypoxia in rats.
AB  - Sleep disordered breathing (SDB), which is characterized by intermittent hypoxia
      (IH) during sleep, causes substantial cardiovascular and neurocognitive
      complications and has become a growing public health problem. SDB is associated
      with suppression of growth hormone (GH) secretion, the latter being integrally
      involved in the growth, development, and function of the CNS. Since GH treatment
      is able to attenuate neurocognitive deficits in a hypoxic-ischemic stroke model,
      GH, GH receptor (GHR) mRNA expression, and GH protein expression were assessed in
      rat hippocampus after exposures to chronic sustained hypoxia (CH, 10% O(2)) or IH
      (10% O(2) alternating with 21% O(2) every 90 s). In addition, the effect of GH
      treatment (50 MUg/kg daily s.c. injection) on erythropoietin (EPO), vascular
      endothelial growth factor (VEGF), heme oxygenase-1 (HO-1), and GLUT-1 mRNA
      expression and neurobehavioral function was assessed. CH significantly increased
      GH mRNA and protein expression, as well as insulin-like growth factor-1 (IGF-1).
      In contrast, IH only induced a moderate increase in GH mRNA and a slight
      elevation in GH protein at day 1, but no increases in IGF-1. CH, but not IH, up
      regulated GHR mRNA in the hippocampus. IH induced marked neurocognitive deficits
      compared with CH or room air (RA). Furthermore, exogenous GH administration
      increased hippocampal mRNA expression of IGF-1, EPO, and VEGF, and not only
      reduced IH-induced hippocampal injury, but also attenuated IH-induced cognitive
      deficits. Thus, exogenous GH may provide a viable therapeutic intervention to
      protect IH-vulnerable brain regions from SDB-associated neuronal loss and
      associated neurocognitive dysfunction.

PMID- 21888953
TI  - Permeability determination and pharmacokinetic study of nobiletin in rat plasma
      and brain by validated high-performance liquid chromatography method.
AB  - In the present study, we are reporting permeability and pharmacokinetics of
      nobiletin in rat plasma and brain, using a validated reverse phase high
      performance liquid chromatographic method. Protein precipitation method was used
      for the extraction of nobiletin and coumarin (IS) from rat plasma and brain
      tissue. The system was run in isocratic mode with mobile phase consisting of
      potassium dihydrogen ortho-phosphate (pH 4.5; 0.04 mM) and acetonitrile in ratio
      of 50:50, v/v. The total chromatographic run time was 9.0 min. The method was
      proved to be accurate and precise at linearity range of 0.05-10 MUg/mL with a
      correlation coefficient (r) of >= 0.994 in rat plasma and >= 0.995 in rat brain.
      The intra- and inter-day precision and accuracy values are found to be within the
      assay variability limits as per the FDA guidelines. Nobiletin was found stable in
      the battery of stability studies viz., bench-top, auto-sampler, freeze/thaw
      cycles and long term storage in a freezer at -70+/-10 degrees C. Maximum
      concentrations of nobiletin in both plasma and brain were observed at 1h after
      single oral dosing (50 mg/kg). The maximum concentration in plasma and brain were
      1.78 and 4.20 MUg/mL, respectively. The AUC(0-t) in plasma and brain were 7.49
      and 20.66 MUg.h/mL, respectively. The mean elimination half life (t(1/2) in
      plasma and brain were 1.80 and 11.42 h, respectively. The Parallel Artificial
      Membrane Permeability Assay (PAMPA) permeability of nobiletin was found to be
      high at both pH 4.0 and 7.0.

PMID- 21888954
TI  - In vitro metabolism in Sprague-Dawley rat liver microsomes of forsythoside A in
      different compositions of Shuang-Huang-Lian.
AB  - Shuang-Huang-Lian (SHL), a traditional Chinese formula containing Lonicerae
      japonicae flos (LJF), Scutellariae radix (SR) and Forsythiae fructus (FF), is
      commonly used to treat acute upper respiratory tract infection, acute bronchitis
      and light pneumonia. Forsythoside A is one of the main active ingredients in
      Forsythiae fructus, a key herb in SHL. In the present study, effects of different
      compositions in SHL on the in vitro metabolism in Sprague-Dawley rat liver
      microsomes of forsythoside A were investigated. The observations from Sprague
      Dawley rat liver microsomes in the presence of beta-NADPH or UDPGA that
      forsythoside A may be the substrates of CYP3A4, CYP2C9, CYP1A2, UGT1A6, UGT1A3,
      UGT1A1 and UGT1A9; Chlorogenic acid may be the substrates of CYP3A4, CYP2C9,
      CYP1A2, CYP2C19, UGT1A6, UGT1A3 and UGT1A1; Baicalin may be the substrates of
      CYP3A4, CYP2C19, CYP1A2, UGT1A9, UGT1A1 and UGT1A3; Baicalein may be the
      substrates of CYP3A4, CYP2E1 and UGT1A6. It was also found that the residue of
      forsythoside A in SHL, FF+LJF and FF+SR was greatly increased compared with that
      in FF in Sprague-Dawley rat liver microsomes in the presence of beta-NADPH or
      UDPGA, which indicated that the metabolism of forsythoside A in SHL may be
      influenced by chlorogenic acid in LJF acting on the CYP3A4, CYP2C9, CYP1A2,
      UGT1A6, UGT1A3 and UGT1A1; baicalin in SR acting on the CYP3A4, CYP1A2, UGT1A9,
      UGT1A1 and UGT1A3; baicalein acting on the CYP3A4 and UGT1A6 respectively.

PMID- 21888955
TI  - Effects of Pinus massoniana bark extract on the adhesion and migration
      capabilities of HeLa cells.
AB  - Pinus massoniana Lamb is a Chinese red pine species used in traditional medicine
      for the treatment of a variety of human health disorders. Recent studies have
      shown that P. massoniana bark extract (PMBE) has an anti-proliferation effect on
      cancer cells. However, it is not clear if PMBE affects cancer cell migration
      and/or invasion. We tested the effect of PMBE, which has B-type procyanidin as
      its main constituent, on the adhesion and migration capabilities of HeLa cells, a
      human cervical cancer cell line, cultured in vitro. Our results showed that PMBE
      has no significant effect on the adhesion capability of HeLa cells, but strongly
      inhibits their migration. This finding suggests that PMBE could be a potential
      therapeutic agent for metastatic cancer.

PMID- 21888957
TI  - WITHDRAWN: Cytochrome P450 CYP3A in marsupials: Characterisation of the first
      identified CYP3A subfamily member, isoform 3A70 from Eastern grey kangaroo
      (Macropus giganteus).
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- 21888956
TI  - Mating increases male's interest in other females: a cognitive study in socially
      monogamous prairie voles (Microtus ochrogaster).
AB  - To determine whether socio-sexual interactions with females influence the male
      prairie vole's cognitive processing, three groups of males were simultaneously
      exposed to sensory stimuli of a control and a focal female then tested for their
      behavioral and neuronal responsiveness to the female cues. From the control
      female, all males received distal cues. From the focal female, the Unmated males
      received distal cues, the Unmated-Contact males received all cues but did not
      mate with her, and the Mated-Contact males received all cues and mated with her.
      Males were tested for their attentiveness to enclosures holding each female and
      for their memory of the females' previous location. Males' brains were then
      examined to localize activated regions following exposure to the odor of familiar
      versus unfamiliar focal females. The Mated-Contact males spent more time in the
      cage of the control female attending to her enclosure than in the cage of the
      focal female. Exposure to odors of unfamiliar focal females activated the
      cingulate cortex of Unmated-Contact males. There was a negative correlation
      between the level of neuronal activation in the retrosplenial cortex of males
      that were exposed to the odors of a familiar focal female and their attentiveness
      to the enclosure of the control female. The data suggest that the effect of socio
      sexual interactions with a female on males' cognition depends on the type of
      sensory signals males receive from females and how individual males perceive
      those signals.

PMID- 21888958
TI  - Recent trends in biomonitoring of bisphenol A, 4-t-octylphenol, and 4
      nonylphenol.
AB  - Bisphenol A (BPA), 4-t-octylphenol (4-t-OP), and 4-nonylphenol (4-NP) are man
      made alkylphenolic environmental contaminants possessing controversial endocrine
      disruption properties. Nowadays, an increased interest is raised for their
      accurate determination in biological media in order to estimate the exposure to
      these compounds and the associated health risk. The aim of this review is to
      present the available analytical methodologies for biomonitoring these three EDCs
      in human population. In non-occupational human exposure, they are detected in
      human matrices in trace level concentrations, commonly lower than 1ng/mL. The use
      of mass spectrometry based methods is particularly emphasized due to their well
      known superiority over sensitivity, selectivity and precision, even in difficult
      matrices, such as blood plasma and serum. Recent and most applicable sample
      preparation techniques are thoroughly presented. The benefits of solid phase
      extraction (SPE) and expected developments are demonstrated. Recent results from
      exposure assessment and epidemiologic studies for BPA, 4-t-OP and 4-NP are
      summarized and future trends are discussed.

PMID- 21888959
TI  - Cognitive deficits induced by melamine in rats.
AB  - Many studies reported that infants and animals were affected by food containing
      melamine, and the renal pathology was the main manifestation in intoxicated case.
      Our previous studies showed that melamine could impair hippocampal function and
      inhibited differentiated PC12 cell proliferation in vitro. The present study
      aimed to examine the effect on hippocampus and the possible mechanism induced by
      melamine in vivo. To address the hypothesis that melamine would impair the
      hippocampal function in vivo and then induce cognitive deficits, male Wistar rats
      were used to establish an animal model and melamine administered at a dose of 300
      mgkg/day for 4 weeks. Morris water maze (MWM) test was employed to evaluate the
      learning and memory. The long term potentiation (LTP) from Schaffer collaterals
      to CA1 region in the hippocampus was recorded. The result of MWM test showed that
      there were significant deficits of learning and memory induced by melamine. LTP
      test presented that field excitatory postsynaptic potentials (fEPSPs) slopes were
      significantly lower in melamine group compared to that in control group. In
      conclusion, melamine had a toxic influence on hippocampus, which induced the
      learning and memory deficits. It suggested that the potential mechanism was
      associated with impairments of synaptic plasticity.

PMID- 21888960
TI  - Preliminary evaluation of a novel oral delivery system for rhPTH1-34: in vitro
      and in vivo.
AB  - rhPTH1-34 is clinically used for osteoporosis treatment. However, this peptide
      drug has no oral bioavailability because of proteolysis and low membrane
      permeability in gastrointestinal gut. This study explored the possibility of
      absorption enhancement for rhPTH1-34 through the oral delivery of the
      microemulsion. The microemulsion (85:15, oil/water) consisting of Labrasol,
      Crodamol GTCC, Solutol HS 15, d-alpha-tocopheryl acetate (6:2:1:1, w/w) and
      saline water was developed and characterized, including particle size,
      morphology, drug loading efficiency and permeability, stability and
      pharmacokinetics. The microemulsion showed high drug loading efficiency (83%) and
      permeability, and significantly higher resistance to proteolysis in vitro study.
      The relative oral bioavailability was 5.4% and 12.0% when delivered to gastric
      and ileum. Besides, osteoporosis rats were induced and treated with oral rhPTH1
      34 microemulsion (0.05 mg/kg), injection (0.01 mg/kg) and vehicle, respectively,
      for 8 weeks. The proximal tibia bone mineral content and density in oral rats
      (0.188 +/- 0.008 g, 0.283 +/- 0.014 g/cm(2)) was significantly increased compared
      to the control rats (0.169 +/- 0.006 g, 0.266 +/- 0.011 g/cm(2)), reaching to the
      sham rats. And the proximal tibia microstructure of oral rats was improved
      greatly, approaching sham level too. These findings revealed that oral
      microemulsion may represent an effective oral delivery system for rhPTH1-34.

PMID- 21888961
TI  - Restoration of 3D vestibular sensation in rhesus monkeys using a multichannel
      vestibular prosthesis.
AB  - Profound bilateral loss of vestibular hair cell function can cause chronically
      disabling loss of balance and inability to maintain stable vision during head and
      body movements. We have previously shown that chinchillas rendered bilaterally
      vestibular-deficient via intratympanic administration of the ototoxic antibiotic
      gentamicin regain a more nearly normal 3-dimensional vestibulo-ocular reflex (3D
      VOR) when head motion information sensed by a head-mounted multichannel
      vestibular prosthesis (MVP) is encoded via rate-modulated pulsatile stimulation
      of vestibular nerve branches. Despite significant improvement versus the unaided
      condition, animals still exhibited some 3D VOR misalignment (i.e., the 3D axis of
      eye movement responses did not precisely align with the axis of head rotation),
      presumably due to current spread between a given ampullary nerve's stimulating
      electrode(s) and afferent fibers in non-targeted branches of the vestibular
      nerve. Assuming that effects of current spread depend on relative orientation and
      separation between nerve branches, anatomic differences between chinchilla and
      human labyrinths may limit the extent to which results in chinchillas accurately
      predict MVP performance in humans. In this report, we describe the MVP-evoked 3D
      VOR measured in alert rhesus monkeys, which have labyrinths that are larger than
      chinchillas and temporal bone anatomy more similar to humans. Electrodes were
      implanted in five monkeys treated with intratympanic gentamicin to bilaterally
      ablate vestibular hair cell mechanosensitivity. Eye movements mediated by the 3D
      VOR were recorded during passive sinusoidal (0.2-5 Hz, peak 50 degrees /s) and
      acceleration-step (1000 degrees /s(2) to 150 degrees /s) whole-body rotations in
      darkness about each semicircular canal axis. During constant 100 pulse/s
      stimulation (i.e., MVP powered ON but set to stimulate each ampullary nerve at a
      constant mean baseline rate not modulated by head motion), 3D VOR responses to
      head rotation exhibited profoundly low gain [(mean eye velocity amplitude)/(mean
      head velocity amplitude) < 0.1] and large misalignment between ideal and actual
      eye movements. In contrast, motion-modulated sinusoidal MVP stimuli elicited a 3D
      VOR with gain 0.4-0.7 and axis misalignment of 21-38 degrees , and responses to
      high-acceleration transient head rotations exhibited gain and asymmetry closer to
      those of unilaterally gentamicin-treated animals (i.e., with one intact
      labyrinth) than to bilaterally gentamicin-treated animals without MVP
      stimulation. In comparison to responses observed under similar conditions in
      chinchillas, acute responses to MVP stimulation in rhesus macaque monkeys were
      slightly better aligned to the desired rotation axis. Responses during combined
      rotation and prosthetic stimulation were greater than when either stimulus was
      presented alone, suggesting that the central nervous system uses MVP input in the
      context of multisensory integration. Considering the similarity in temporal bone
      anatomy and VOR performance between rhesus monkeys and humans, these observations
      suggest that an MVP will likely restore a useful level of vestibular sensation
      and gaze stabilization in humans.

PMID- 21888963
TI  - Rice functional genomics research: progress and implications for crop genetic
      improvement.
AB  - Rice is a staple food crop and has become a reference of monocot plant for
      functional genomic research. With the availability of high quality rice genome
      sequence, there has been rapid accumulation of functional genomic resources,
      including: large mutant libraries by T-DNA insertion, transposon tagging, and
      chemical mutagenesis; global expression profiles of the genes in the entire life
      cycle of rice growth and development; full-length cDNAs for both indica and
      japonica rice; sequences from resequencing large numbers of diverse germplasm
      accessions. Such resource development has greatly accelerated gene cloning. By
      the end of 2010, over 600 genes had been cloned using various methods. Many of
      the genes control agriculturally useful traits such as yield, grain quality,
      resistances to biotic and abiotic stresses, and nutrient-use efficiency, thus
      have potential utility in crop genetic improvement. This review was aimed to
      provide a comprehensive summary of such progress. We also presented our
      perspective for future studies.

PMID- 21888962
TI  - Plant adaptation to dynamically changing environment: the shade avoidance
      response.
AB  - The success of competitive interactions between plants determines the chance of
      survival of individuals and eventually of whole plant species. Shade-tolerant
      plants have adapted their photosynthesis to function optimally under low-light
      conditions. These plants are therefore capable of long-term survival under a
      canopy shade. In contrast, shade-avoiding plants adapt their growth to perceive
      maximum sunlight and therefore rapidly dominate gaps in a canopy. Daylight
      contains roughly equal proportions of red and far-red light, but within
      vegetation that ratio is lowered as a result of red absorption by photosynthetic
      pigments. This light quality change is perceived through the phytochrome system
      as an unambiguous signal of the proximity of neighbors resulting in a suite of
      developmental responses (termed the shade avoidance response) that, when
      successful, result in the overgrowth of those neighbors. Shoot elongation induced
      by low red/far-red light may confer high relative fitness in natural dense
      communities. However, since elongation is often achieved at the expense of leaf
      and root growth, shade avoidance may lead to reduction in crop plant
      productivity. Over the past decade, major progresses have been achieved in the
      understanding of the molecular basis of shade avoidance. However, uncovering the
      mechanisms underpinning plant response and adaptation to changes in the ratio of
      red to far-red light is key to design new strategies to precise modulate shade
      avoidance in time and space without impairing the overall crop ability to compete
      for light.

PMID- 21888964
TI  - Neuroimmunological response of beluga whales (Delphinapterus leucas) to
      translocation and a novel social environment.
AB  - This study assessed changes in phagocyte function and activation of the sympatho
      adrenal medullary and hypothalamo-pituitary adrenal axes of beluga whales
      (Delphinapterus leucas) in response to translocation and introduction to a novel
      social environment. Transported belugas exhibited increases in epinephrine (E),
      norepinephrine (NE), and cortisol levels in response to the translocation
      process. In response to the introduction of the transported belugas, resident
      belugas exhibited an increase in E and NE but not cortisol. Moreover, the
      increase in E and NE shown by the transported belugas was significantly greater
      than the increase exhibited by the resident belugas. Resident belugas exhibited a
      concomitant decrease in neutrophil and monocyte phagocytosis associated with the
      introduction of the transported belugas. In contrast, transported belugas
      exhibited an attendant increase in phagocytosis and respiratory burst activity
      immediately following transport. Differences in phagocyte response may derive
      from differences in hormonal milieu, stressor modality and/or intensity, or
      phagocyte priming. Investigating the complex interactions between types of
      stressors, neuroendocrine response, and immunocompetence will lead to a better
      understanding of the impacts of environmental challenges, including anthropogenic
      perturbations, on the health of cetacean populations.

PMID- 21888965
TI  - Imbalance between sympathetic and sensory innervation in peritoneal
      endometriosis.
AB  - To investigate possible mechanisms of pain pathophysiology in patients with
      peritoneal endometriosis, a clinical study on sensory and sympathetic nerve fibre
      sprouting in endometriosis was performed. Peritoneal lesions (n=40) and healthy
      peritoneum (n=12) were immunostained and analysed with anti-protein gene product
      9.5 (PGP 9.5), anti-substance P (SP) and anti-tyrosine hydroxylase (TH), specific
      markers for intact nerve fibres, sensory nerve fibres and sympathetic nerve
      fibres, respectively, to identify the ratio of sympathetic and sensory nerve
      fibres. In addition, immune cell infiltrates in peritoneal endometriotic lesions
      were analysed and the nerve growth factor (NGF) and interleukin (IL)-1beta
      expression was correlate with the nerve fibre density. Peritoneal fluids from
      patients with endometriosis (n=40) and without endometriosis (n=20) were used for
      the in vitro neuronal growth assay. Cultured chicken dorsal root ganglia (DRG)
      and sympathetic ganglia were stained with anti-growth associated protein 43 (anti
      GAP 43), anti-SP and anti-TH. We could detect an increased sensory and decreased
      sympathetic nerve fibres density in peritoneal lesions compared to healthy
      peritoneum. Peritoneal fluids of patients with endometriosis compared to patients
      without endometriosis induced an increased sprouting of sensory neurites from DRG
      and decreased neurite outgrowth from sympathetic ganglia. In conclusion, this
      study demonstrates an imbalance between sympathetic and sensory nerve fibres in
      peritoneal endometriosis, as well as an altered modulation of peritoneal fluids
      from patients with endometriosis on sympathetic and sensory innervation which
      might directly be involved in the maintenance of inflammation and pain.

PMID- 21888966
TI  - Estimation of the effective intercellular diffusion coefficient in cell
      monolayers coupled by gap junctions.
AB  - OBJECTIVE: A recently developed dye-based assay to study gap junction
      permeability is analysed. The assay is based on electroporation of dye into a
      large number of connexin 43 expressing cells, grown to confluency on electrically
      conductive slides. The subsequent intercellular spread of dye to non
      electroporated parts of the monolayer enables estimation of the intercellular
      coupling. So far, the extent of dye spread has been analyzed in qualitative terms
      only and not in a manner based directly on the physics of the underlying
      diffusion process. METHODS: We apply a continuum approximation assuming that the
      observed dye spread can be described by Fick's law of diffusion. Deduced from
      Fick's law, new measures are presented which directly relate the observed spread
      of dye to the diffusion coefficient. RESULTS: The theoretical framework enables
      the estimation of an effective diffusion coefficient from Fick's law
      independently of the specific indicator substance used in the assay. For Lucifer
      Yellow, diffusion stops within few minutes after the electroporation. Therefore
      only an order-of-magnitude estimate of the diffusion coefficient can be given for
      this dye. CONCLUSION: In terms of the underlying diffusion coefficient, the
      hitherto used measures give a relatively poor degree of quantification. In
      contrast, the present methods may yield direct information on the effective
      intercellular diffusion coefficient and hence provide additional and more precise
      information as to the permeability modulating effect of various substances.

PMID- 21888967
TI  - The encapsulation of beta-lapachone in 2-hydroxypropyl-beta-cyclodextrin
      inclusion complex into liposomes: a physicochemical evaluation and molecular
      modeling approach.
AB  - The aim of this study was to encapsulate lapachone (beta-lap) or inclusion
      complex (beta-lap:HPbeta-CD) in liposomes and to evaluate their physicochemical
      characteristics. In addition, the investigation of the main aspects of the
      interaction between beta-lap and 2-hydroxypropyl-beta-cyclodextrin (HPbeta-CD),
      using both experimental and molecular modeling approaches was discussed.
      Furthermore, the in vitro drug release kinetics was evaluated. First, a phase
      solubility study of beta-lap in HPbeta-CD was performed and the beta-lap:HPbeta
      CD was prepared by the freeze-drying technique. A 302-fold increase of solubility
      was achieved for beta-lap in HPbeta-CD solution with a constant of association
      K(1:1) of 961 M(-1) and a complexation efficiency of beta-lap of 0.1538. (1)H
      NMR, TG, DSC, IR, Raman and SEM indicated a change in the molecular environment
      of beta-lap in the inclusion complex. Molecular modeling confirms these results
      suggesting that beta-lap was included in the cavity of HPbeta-CD, with an
      intermolecular interaction energy of -23.67 kJ mol(-1). beta-lap:HPbeta-CD and
      beta-lap-loaded liposomes presented encapsulation efficiencies of 93% and 97%,
      respectively. The kinetic rate constants of 183.95+/-1.82 MUg/h and 216.25+/-2.34
      MUg/h were calculated for beta-lap and beta-lap:HPbeta-CD-loaded liposomes,
      respectively. In conclusion, molecular modeling elucidates the formation of the
      inclusion complex, stabilized through hydrogen bonds, and the encapsulation of
      beta-lap and beta-lap:HPbeta-CD into liposomes could provide an alternative means
      leading eventually to its use in cancer research.

PMID- 21888968
TI  - Virtual tissue engineering of the human atrium: modelling pharmacological actions
      on atrial arrhythmogenesis.
AB  - Computational models of human atrial cells, tissues and atria have been
      developed. Cell models, for atrial wall, crista terminalis, appendage, Bachmann's
      bundle and pectinate myocytes are characterised by action potentials, ionic
      currents and action potential duration (APD) restitution. The principal effect of
      the ion channel remodelling of persistent atrial fibrillation (AF), and a
      mutation producing familial AF, was APD shortening at all rates. Electrical
      alternans was abolished by the modelled action of Dronedarone. AF induced gap
      junctional remodelling slows propagation velocity at all rates. Re-entrant spiral
      waves in 2-D models are characterised by their frequency, wavelength, meander and
      stability. For homogenous models of normal tissue, spiral waves self-terminate,
      due to meander to inexcitable boundaries, and by dissipation of excitation. AF
      electrical remodelling in these homogenous models led to persistence of spiral
      waves, and AF fibrotic remodelling to their breakdown into fibrillatory activity.
      An anatomical model of the atria was partially validated by the activation times
      of normal sinus rhythm. The use of tissue geometry from clinical MRI, and tissue
      anisotropy from ex vivo diffusion tensor magnetic resonance imaging is outlined.
      In the homogenous model of normal atria, a single scroll breaks down onto spatio
      temporal irregularity (electrical fibrillation) that is self-terminating; while
      in the AF remodelled atria the fibrillatory activity is persistent. The
      persistence of electrical AF can be dissected in the model in terms of ion
      channel and intercellular coupling processes, that can be modified
      pharmacologically; the effects of anatomy, that can be modified by ablation; and
      the permanent effects of fibrosis, that need to be prevented.

PMID- 21888970
TI  - Simulating kinetic parameters in transporter mediated permeability across Caco-2
      cells. A case study of estrone-3-sulfate.
AB  - Substances that compete for the same saturable intestinal transporters may when
      dosed together lead to altered permeability and hence influence bioavailability.
      The aim was to simulate kinetic parameters, i.e. K(m) and J(max), for transporter
      mediated E(1)S permeability across Caco-2 cells by a combined experimental
      modeling approach. 4 classes of transporters were suggested to be involved in the
      permeability of E(1)S, i.e. apical influx (T(I)) and efflux (T(III)) as well as
      basolateral efflux (T(II)) and influx (T(IV)). Efflux ratio of E(1)S was
      determined to 6.8. E(1)S is suggested to have highest affinity to T(III). T(IV)
      is however suggested to be rate limiting in exsorptive P(APP) due to lower J(max)
      of T(IV), compared to T(III). Possible interactions between E(1)S and the
      excipients erythrosine and Brij35 on these 4 classes of transporters were also
      studied. From these studies it is suggested that erythrosine does interact with
      E(1)S on apical efflux transporter T(III) by competitive inhibition. Furthermore
      interaction between erythrosine and E(1)S is suggested on apical influx
      transporter (T(I)). Brij35 does not seem to interact with E(1)S on apical
      transporters. The present model seem to be a valuable tool to simulate kinetic
      parameters for compounds being substrates to multiple transporters as well as to
      estimate kinetic parameters for compounds interacting on the same transporters.

PMID- 21888969
TI  - A mathematical modelling approach to assessing the reliability of biomarkers of
      glutathione metabolism.
AB  - One of the main pathways for the detoxification of reactive metabolites in the
      liver involves glutathione conjugation. Metabolic profiling studies have shown
      paradoxical responses in glutathione-related biochemical pathways. One of these
      is the increase in 5-oxoproline and ophthalmic acid concentrations with increased
      dosage of paracetamol. Experimental studies have thus far failed to resolve these
      paradoxes and the robustness of how these proposed biomarkers correlate with
      liver glutathione levels has been questioned. To better understand how these
      biomarkers behave in the glutathione system a kinetic model of this pathway was
      made. By using metabolic control analysis and by simulating biomarker levels
      under a variety of conditions, we found that 5-oxoproline and ophthalmic acid
      concentrations may not only depend on the glutathione but also on the methionine
      status of the cell. We show that neither of the two potential biomarkers are
      reliable on their own since they need additional information about the methionine
      status of the system to relate them uniquely to intracellular glutathione
      concentration. However, when both biomarkers are measured simultaneously a direct
      inference of the glutathione concentration can be made, irrespective of the
      methionine concentration in the system.

PMID- 21888971
TI  - License to kill: Formulation requirements for optimal priming of CD8(+) CTL
      responses with particulate vaccine delivery systems.
AB  - Induction of CD8(+) T-cell responses is critical for the immunological control of
      a variety of diseases upon vaccination. Modern subunit vaccines are based on
      highly purified recombinant proteins. The high purity represents a major
      advancement in terms of vaccine safety compared to previous vaccination
      strategies with live attenuated or whole killed pathogens, but typically renders
      vaccine antigens poorly immunogenic and insufficient in mobilizing protective
      immunity. Adjuvants are therefore needed in vaccine formulations to enhance,
      direct and maintain the immune response to vaccine antigens. However, a weakness
      of many adjuvants is the lack of induction of CD8(+) T-cell responses against
      protein antigens, which are required for protection against challenging and
      difficult infectious diseases such as AIDS and for therapeutic cancer
      vaccination. Within the last decade, adjuvant systems that can induce CD8(+) T
      cell responses have been developed and the first clinical trials demonstrating
      the clinical relevance of such formulations have been performed. This paper
      reviews the current status of lipid- and polymer-based particulate antigen
      delivery systems capable of stimulating CD8(+) T-cell immunity with special focus
      on mechanisms of priming and pharmaceutical requirements for optimal activation
      of cytotoxic T-lymphocytes that can kill virus-infected or abnormal (cancer)
      cells.

PMID- 21888972
TI  - Expert opinion: Responsive polymer nanoparticles in cancer therapy.
AB  - Polymeric nanoparticles are emerging as an attractive treatment options for
      cancer due to their favorable size distribution, drug carrying capacity, and
      tunable properties. In particular, intelligent nanoparticles that respond to
      biological cues are of interest because of their ability to provide controlled
      release at a specific site. Tumor sites display abnormal pH profiles and
      pathophysiology that can be exploited to provide localized release. In this
      expert opinion, we discuss passive and active targeting of nanoparticles and
      several classes of pH-responsive nanoparticles.

PMID- 21888973
TI  - Advances in the understanding of the structure and function of ER-alpha36,a novel
      variant of human estrogen receptor-alpha.
AB  - Estrogen receptors (ERs) belong to the nuclear receptor superfamily, whose
      members include ER-alpha66, ER-alpha36, ER-alpha46 and ER-beta. Each receptor
      performs specific functions through binding with a specific ligand, such as
      estrogen. Recently, ER-alpha36, a novel variant of human estrogen receptor-alpha
      (ER-alpha), was identified and cloned. ER-alpha36 inhibits, in a dominant
      negative manner, the transactivation of both the wild-type ER-alpha (ER-alpha66)
      and ER-beta. As a predominantly membrane-based ER, ER-alpha36 mediates nongenomic
      estrogen signaling and is involved in the resistance of breast cancer to
      endocrine therapy, i.e., tamoxifen. This review summarizes recent studies on the
      structure and function of ER-alpha36 and the relationship of ER-alpha36 with
      cancer, with special emphasis on its function in the resistance of breast cancer
      to endocrine therapy.

PMID- 21888974
TI  - Purification, cDNA structure and biological significance of a single insulin-like
      growth factor-binding domain protein (SIBD-1) identified in the hemocytes of the
      spider Cupiennius salei.
AB  - Cupiennius salei single insulin-like growth factor-binding domain protein (SIBD
      1), which exhibits an IGFBP N-terminal domain-like profile, was identified in the
      hemocytes of the spider C. salei. SIBD-1 was purified by RP-HPLC and the sequence
      determined by a combination of Edman degradation and 5'-3'- RACE PCR. The peptide
      (8676.08 Da) is composed of 78 amino acids, contains six intrachain disulphide
      bridges and carries a modified Thr residue at position 2. SIBD-1 mRNA expression
      was detected by quantitative real-time PCR mainly in hemocytes, but also in the
      subesophageal nerve mass and muscle. After infection, the SIBD-1 content in the
      hemocytes decreases and, simultaneously, the temporal SIBD-1 expression seems to
      be down-regulated. Two further peptides, SIBD-2 and IGFBP-rP1, also exhibiting
      IGFBP N-terminal domain variants with unknown functions, were identified on cDNA
      level in spider hemocytes and venom glands. We conclude that SIBD-1 may play an
      important role in the immune system of spiders.

PMID- 21888975
TI  - The structural basis of the two-dimensional net pattern observed in the X-ray
      diffraction pattern of avian keratin.
AB  - Feather keratin has a composite structure with a filament-matrix texture, and
      transmission electron microscopy studies of thin transverse sections of feather
      rachis by Rogers and Filshie in the early 1960s showed that the filaments have a
      strong tendency to form sheets. Potentially this could account for the unusual X
      ray diffraction pattern noted by Bear and Rugo in the early 1950s, which was
      interpreted by them as indicating a two-dimensional net structure. Although it is
      50years since these major advances were made the possibility of extracting
      information on the nature of the filament packing from the diffraction pattern
      has never been explored. The present contribution shows how, when taken together
      with current information on the nature of beta-sheets in feather keratin, certain
      features of the X-ray diffraction pattern can now be used to determine the likely
      arrangement of the filaments in the sheet.

PMID- 21888976
TI  - Antigenic identification of virion structural proteins from infectious spleen and
      kidney necrosis virus.
AB  - Infectious spleen and kidney necrosis virus (ISKNV), belonging to the genus
      Megalocytivirus in the family Iridoviridae, is one of the major agents causing
      mortality and economic losses to the freshwater fish culture industry in Asian
      countries. Currently, little information regarding the antigenic properties of
      Megalocytivirus (especially ISKNV) is available. Our previous study using four
      different workflows with systematic and comprehensive proteomic approaches led to
      the identification of 38 ISKNV virion-associated proteins (J. Virol. 2869-2877,
      2011). Thus, in this report, the antigenicity of 31 structural proteins from
      ISKNV virion was investigated. A one-dimensional gel electrophoresis immunoblot
      profile coupled with MALDI-TOF-TOF MS/MS was applied to identify six immunogenic
      viral proteins, namely, ORFs major capsid protein (006L), 054L, 055L, 101L, 117L,
      and 125L. Then, the antigenicity of 31 structural proteins was characterized by
      Western blot by using pooled sera from mandarin fish that survived ISKNV
      infection. Of the 31 viral proteins, 22 were recognized by the fish ISKNV
      antiserum. Furthermore, this antiserum neutralizes MFF-1 cells ISKNV infection.
      To our knowledge, this study is the first report on the immunogenicity of viral
      proteins and characterization of the proteome of megalocytivirus infective
      agents. Our findings are expected to promote the development of effective vaccine
      candidates.

PMID- 21888977
TI  - Dietary supplementation with Cynodon dactylon (L.) enhances innate immunity and
      disease resistance of Indian major carp, Catla catla (Ham.).
AB  - Indian major carp (Catla catla) was subjected to study the immunostimulatory
      effects when the grass Cynodon dactylon(L) ethanolic extract administrated as
      feed supplement. C. catla was fed with 0% (Control), 0.05% (group I), 0.5% (group
      II) and 5% (group III) extract provided for 60 days. Blood samples were collected
      at every 10 days of interval up to 60 days for analyzing the non-specific humoral
      (lysozyme activity, antiprotease activity and haemolytic complement) and cellular
      (production of reactive oxygen and nitrogen species, myeloperoxidase activity)
      immune response study. The results indicate that C. dactylon ethanolic extract
      administered as feed supplement significantly (P < 0.05) enhanced most of the non
      specific immune parameters tested. Among the experimental diet groups,
      significantly increased response of non-specific immunity was seen in group III
      (5%). Disease resistant analysis against Aeromonas hydrophila was performed in
      control group and plant extract treated fish for 7, 14, 21 and 28 days. Relative
      percent survival rate (RPS) was observed in treated samples, which is directly
      proportional to concentration of the extract. Additionally, electron microscopic
      studies and gelatin zymography for Matrix Metalo Proteinase (MMPs) were examined
      in spleen at 7th and 28th days of feeding. Administration of C. dactylon mixed
      diet delayed the lymphocyte destruction with positive ultrastructural changes. An
      induced stress (A. hydrophila infection) was observed by using MMPs expression,
      which was reduced in the experimental diet groups than the control. All these
      experimental results prove that C. dactylon ethanolic extract enhances the
      immunity of Catla fish.

PMID- 21888978
TI  - Alpha2-macroglobulin from an Atlantic shrimp: biochemical characterization, sub
      cellular localization and gene expression upon fungal challenge.
AB  - In this study, we report on the isolation and characterization of an alpha2
      macroglobulin (alpha2M) from the plasma of the pink shrimp Farfantepenaeus
      paulensis, its sub-cellular localization and transcriptional changes after
      infection by fungi. The molecular mass of the alpha2M was estimated at 389 kDa by
      gel filtration and 197 kDa by SDS-PAGE, under reducing conditions, suggesting
      that alpha2M from F. paulensis consists of two identical sub-units, covalently
      linked by disulphide bonds. The N-terminal amino acid sequence of the alpha2M
      from F. paulensis was very similar to those of other penaeid shrimps, crayfish
      and lobster (70-90% identity) and to a less extent with that of freshwater prawn
      (40% identity). A monoclonal antibody raised against the Marsupenaeus japonicus
      alpha2M made it possible to demonstrate that alpha2M of F. paulensis is stored in
      the vesicles of the shrimp granular hemocytes (through immunogold assay).
      Quantitative real-time PCR (qPCR) analysis showed that alpha2M mRNA transcripts
      significantly increased 24 h after an experimental infection with the shrimp
      pathogen Fusarium solani and it returned to the basal levels at 48 h post
      injection. This is the first report on a alpha2M characterization in an Atlantic
      penaeid species and its expression profile upon a fungal infection.

PMID- 21888979
TI  - Distinct pathways of neural coupling for different basic emotions.
AB  - Emotions are complex events recruiting distributed cortical and subcortical
      cerebral structures, where the functional integration dynamics within the
      involved neural circuits in relation to the nature of the different emotions are
      still unknown. Using fMRI, we measured the neural responses elicited by films
      representing basic emotions (fear, disgust, sadness, happiness). The amygdala and
      the associative cortex were conjointly activated by all basic emotions.
      Furthermore, distinct arrays of cortical and subcortical brain regions were
      additionally activated by each emotion, with the exception of sadness. Such
      findings informed the definition of three effective connectivity models, testing
      for the functional integration of visual cortex and amygdala, as regions
      processing all emotions, with domain-specific regions, namely: i) for fear, the
      frontoparietal system involved in preparing adaptive motor responses; ii) for
      disgust, the somatosensory system, reflecting protective responses against
      contaminating stimuli; iii) for happiness: medial prefrontal and temporoparietal
      cortices involved in understanding joyful interactions. Consistently with these
      domain-specific models, the results of the effective connectivity analysis
      indicate that the amygdala is involved in distinct functional integration effects
      with cortical networks processing sensorimotor, somatosensory, or cognitive
      aspects of basic emotions. The resulting effective connectivity networks may
      serve to regulate motor and cognitive behavior based on the quality of the
      induced emotional experience.

PMID- 21888980
TI  - Componential Granger causality, and its application to identifying the source and
      mechanisms of the top-down biased activation that controls attention to affective
      vs sensory processing.
AB  - We describe a new measure of Granger causality, componential Granger causality,
      and show how it can be applied to the identification of the directionality of
      influences between brain areas with functional neuroimaging data. Componential
      Granger causality measures the effect of y on x, but allows interaction effects
      between y and x to be measured. In addition, the terms in componential Granger
      causality sum to 1, allowing causal effects to be directly compared between
      systems. We show using componential Granger causality analysis applied to an fMRI
      investigation that there is a top-down attentional effect from the anterior
      dorsolateral prefrontal cortex to the orbitofrontal cortex when attention is paid
      to the pleasantness of a taste, and that this effect depends on the activity in
      the orbitofrontal cortex as shown by the interaction term. Correspondingly there
      is a top-down attentional effect from the posterior dorsolateral prefrontal
      cortex to the insular primary taste cortex when attention is paid to the
      intensity of a taste, and this effect depends on the activity of the insular
      primary taste cortex as shown by the interaction term. Componential Granger
      causality thus not only can reveal the directionality of effects between areas
      (and these can be bidirectional), but also allows the mechanisms to be understood
      in terms of whether the causal influence of one system on another depends on the
      state of the system being causally influenced. Componential Granger causality
      measures the full effects of second order statistics by including variance and
      covariance effects between each time series, thus allowing interaction effects to
      be measured, and also provides a systematic framework within which to measure the
      effects of cross, self, and noise contributions to causality. The findings reveal
      some of the mechanisms involved in a biased activation theory of selective
      attention.

PMID- 21888981
TI  - Large scale brain activations predict reasoning profiles.
AB  - Deduction is the ability to draw necessary conclusions from previous knowledge.
      Here we propose a novel approach to understanding the neural basis of deduction,
      which exploits fine-grained inter-participant variability in such tasks.
      Participants solved deductive problems and were grouped by the behavioral
      strategies employed, i.e., whether they were sensitive to the logical form of
      syllogistic premises, whether the problems were solved correctly, and whether
      heuristic strategies were employed. Differential profiles of neural activity can
      predict membership of the first two of these groups. The predictive power of
      activity profiles is distributed non-uniformly across the brain areas activated
      by deduction. Activation in left ventro-lateral frontal (BA47) and lateral
      occipital (BA19) cortices predicts whether logically valid solutions are sought.
      Activation of left inferior lateral frontal (BA44/45) and superior medial frontal
      (BA6/8) cortices predicts sensitivity to the logical structure of problems. No
      specific pattern of activation was associated with the use of a non-logical
      heuristic strategy. Not only do these findings corroborate the hypothesis that
      left BA47, BA44/45 and BA6/8 are critical for making syllogistic deductions, but
      they also imply that they have different functional roles as components of a
      dedicated network. We propose that BA44/45 and BA6/8 are involved in the
      extraction and representation of the formal structure of a problem, while BA47 is
      involved in the selection and application of relevant inferential rules. Finally,
      our findings suggest that deductive reasoning can be best described as a cascade
      of cognitive processes requiring the concerted operation of several, functionally
      distinct, brain areas.

PMID- 21888982
TI  - Do distinct atypical cortical networks process biological motion information in
      adults with Autism Spectrum Disorders?
AB  - Whether people with Autism Spectrum Disorders (ASDs) have a specific deficit when
      processing biological motion has been a topic of much debate. We used
      psychophysical methods to determine individual behavioural thresholds in a point
      light direction discrimination paradigm for a small but carefully matched groups
      of adults (N=10 per group) with and without ASDs. These thresholds were used to
      derive individual stimulus levels in an identical fMRI task, with the purpose of
      equalising task performance across all participants whilst inside the scanner.
      The results of this investigation show that despite comparable behavioural
      performance both inside and outside the scanner, the group with ASDs shows a
      different pattern of BOLD activation from the TD group in response to the same
      stimulus levels. Furthermore, connectivity analysis suggests that the main
      differences between the groups are that the TD group utilise a unitary network
      with information passing from temporal to parietal regions, whilst the ASD group
      utilise two distinct networks; one utilising motion sensitive areas and another
      utilising form selective areas. Furthermore, a temporal-parietal link that is
      present in the TD group is missing in the ASD group. We tentatively propose that
      these differences may occur due to early dysfunctional connectivity in the brains
      of people with ASDs, which to some extent is compensated for by rewiring in high
      functioning adults.

PMID- 21888983
TI  - Test-retest reliability of resting-state connectivity network characteristics
      using fMRI and graph theoretical measures.
AB  - Characterizing the brain connectome using neuroimaging data and measures derived
      from graph theory emerged as a new approach that has been applied to brain
      maturation, cognitive function and neuropsychiatric disorders. For a broad
      application of this method especially for clinical populations and longitudinal
      studies, the reliability of this approach and its robustness to confounding
      factors need to be explored. Here we investigated test-retest reliability of
      graph metrics of functional networks derived from functional magnetic resonance
      imaging (fMRI) recorded in 33 healthy subjects during rest. We constructed
      undirected networks based on the Anatomic-Automatic-Labeling (AAL) atlas template
      and calculated several commonly used measures from the field of graph theory,
      focusing on the influence of different strategies for confound correction. For
      each subject, method and session we computed the following graph metrics:
      clustering coefficient, characteristic path length, local and global efficiency,
      assortativity, modularity, hierarchy and the small-worldness scalar. Reliability
      of each graph metric was assessed using the intraclass correlation coefficient
      (ICC). Overall ICCs ranged from low to high (0 to 0.763) depending on the method
      and metric. Methodologically, the use of a broader frequency band (0.008-0.15 Hz)
      yielded highest reliability indices (mean ICC=0.484), followed by the use of
      global regression (mean ICC=0.399). In general, the second order metrics (small
      worldness, hierarchy, assortativity) studied here, tended to be more robust than
      first order metrics. In conclusion, our study provides methodological
      recommendations which allow the computation of sufficiently robust markers of
      network organization using graph metrics derived from fMRI data at rest.

PMID- 21888984
TI  - hERG potency estimates based upon dose solution analysis: What have we learned?
AB  - INTRODUCTION: Measurement of drug-induced inhibition of potassium current flow
      through the hERG channel is used to determine potency at the channel, which is
      used as an in vitro risk assessment for QTc interval prolongation in vivo. In the
      hERG assay, test solutions of varying strength are prepared to construct a
      concentration-response curve based upon the nominal drug concentration (NOM).
      Dose-solution analysis (DSA) is an analytical approach to confirm the test
      concentration achieved in an in vitro assay (Herron, Towers, & Templeton, 2004),
      and can be included as a component of hERG channel study to confirm drug
      concentration in the assay buffer to determine potency using the "actual" drug
      level in solution (ACT). Thus, DSA could be helpful in confirming test article
      concentrations. This study examined whether inclusion of DSA improved the
      accuracy of potency estimates based upon the ACT compared to the NOM
      concentration during hERG voltage clamp assays (non-GLP) for 99 diverse agents.
      METHODS: We examined the correlation of hERG IC(50) derived from NOM with hERG
      IC(50) derived from ACT, and analyzed potential mechanisms of deviation between
      ACT and NOM potency values, including solubility, cLogP, PKa, and molecular
      weights. RESULTS: Seventy-four (74) of 99 agents (73.7%) had NOM- and ACT-derived
      IC(50) values within 3-fold, 87 of 99 (87.8%) had an IC(50) ratio within 10-fold,
      and 12 (12.1%) had a >10-fold difference in their NOM IC(50) and ACT IC(50)
      values. On average, these 12 compounds had less soluble, more lipophilic (high
      cLogP values), and more basic characters (high pKa values). DISCUSSION: Our
      investigation indicated that DSA did not alter hERG potency estimation for the
      majority of compounds in this dataset, i.e., DSA confirmed the NOM concentration
      within 3-fold. For poorly soluble agents or agents with high cLogP and pKa
      values, however, DSA did not clarify or improve hERG potency estimates.

PMID- 21888985
TI  - The 14-3-3 proteins in regulation of cellular metabolism.
AB  - Thirty years ago, it was discovered that 14-3-3 proteins could activate enzymes
      involved in amino acid metabolism. In the following decades, 14-3-3s have been
      shown to be involved in many different signaling pathways that modulate cellular
      and whole body energy and nutrient homeostasis. Large scale screening for
      cellular binding partners of 14-3-3 has identified numerous proteins that
      participate in regulation of metabolic pathways, although only a minority of
      these targets have yet been subject to detailed studies. Because of the wide
      distribution of potential 14-3-3 targets and the resurging interest in metabolic
      pathway control in diseases like cancer, diabetes, obesity and cardiovascular
      disease, we review the role of 14-3-3 proteins in the regulation of core and
      specialized cellular metabolic functions. We cite illustrative examples of 14-3-3
      action through their direct modulation of individual enzymes and through
      regulation of master switches in cellular pathways, such as insulin signaling,
      mTOR- and AMP dependent kinase signaling pathways, as well as regulation of
      autophagy. We further illustrate the quantitative impact of 14-3-3 association on
      signal response at the target protein level and we discuss implications of recent
      findings showing 14-3-3 protein membrane binding of target proteins.

PMID- 21888986
TI  - The biomarker is not the end.
AB  - As drug discovery and translational scientists think about using stratification
      with biomarkers to improve the chances of getting medicines to patients, several
      areas of expertise need to be considered. These include analytical validation,
      clinical validation, regulatory affairs and intellectual property. Getting the
      right input from the right expert at the right time can make or break an effort
      to bring a biomarker-based companion diagnostic successfully into clinical
      practice.

PMID- 21888987
TI  - Drug-diagnostic co-development: how to harness the value.
AB  - Some years ago, we developed a value assessment process that was predicated on
      certain assumptions about how valuation might be influenced by drug development
      and marketing factors. Here, we discuss how our assumptions have held up
      particularly in light of regulatory and reimbursement changes. In addition, we
      assess how the relationship models derived from the value-assessment process have
      been substantiated by reviewing some recent cases of testing and stratification.

PMID- 21888988
TI  - Considerations for safety pharmacogenetics in clinical practice.
AB  - The focus of treating an individual patient is the identification of the
      individual's specific needs. The measurement of the patient's characteristics,
      such as blood pressure or body temperature, and also the measurement of
      biomarkers, such as cholesterol or hemoglobin A1C is part of the patient's health
      assessment. The deeper the insights into the phenotypic and molecular
      characteristics of the patient, the better we are positioned to treat a patient.
      Increasingly, this assessment includes testing for certain pharmacologically
      relevant genetic variations (pharmacogenetics). Evaluating how the patient's
      genetic makeup combined with the patient's exposure to environmental influences
      could impact disease and treatment decisions is becoming the cornerstone of
      personalized medicine. However, we often use such assessments for finding the
      most 'effective' treatment, but we might not always be as rigorous in our
      assessment of potential safety risks. This is particularly apparent when looking
      at how safety risks are communicated. Often this information is only available as
      general, population-based statements and a small amount of information is
      available to evaluate whether or not an individual patient is at risk. Although
      pharmacogenetic tests that can help to assess whether an individual patient's
      personal risk exist (safety pharmacogenetics), they are not always performed.

PMID- 21888989
TI  - Integrating clinical research with the Healthcare Enterprise: from the RE-USE
      project to the EHR4CR platform.
AB  - BACKGROUND: There are different approaches for repurposing clinical data
      collected in the Electronic Healthcare Record (EHR) for use in clinical research.
      Semantic integration of "siloed" applications across domain boundaries is the
      raison d'etre of the standards-based profiles developed by the Integrating the
      Healthcare Enterprise (IHE) initiative - an initiative by healthcare
      professionals and industry promoting the coordinated use of established standards
      such as DICOM and HL7 to address specific clinical needs in support of optimal
      patient care. In particular, the combination of two IHE profiles - the
      integration profile "Retrieve Form for Data Capture" (RFD), and the IHE content
      profile "Clinical Research Document" (CRD) - offers a straightforward approach to
      repurposing EHR data by enabling the pre-population of the case report forms
      (eCRF) used for clinical research data capture by Clinical Data Management
      Systems (CDMS) with previously collected EHR data. OBJECTIVE: Implement an
      alternative solution of the RFD-CRD integration profile centered around two
      approaches: (i) Use of the EHR as the single-source data-entry and persistence
      point in order to ensure that all the clinical data for a given patient could be
      found in a single source irrespective of the data collection context, i.e.
      patient care or clinical research; and (ii) Maximize the automatic pre-population
      process through the use of a semantic interoperability services that identify
      duplicate or semantically-equivalent eCRF/EHR data elements as they were
      collected in the EHR context. METHODS: The RE-USE architecture and associated
      profiles are focused on defining a set of scalable, standards-based, IHE
      compliant profiles that can enable single-source data collection/entry and cross
      system data reuse through semantic integration. Specifically, data reuse is
      realized through the semantic mapping of data collection fields in electronic
      Case Report Forms (eCRFs) to data elements previously defined as part of patient
      care-centric templates in the EHR context. The approach was evaluated in the
      context of a multi-center clinical trial conducted in a large, multi-disciplinary
      hospital with an installed EHR. RESULTS: Data elements of seven eCRFs used in a
      multi-center clinical trial were mapped to data elements of patient care-centric
      templates in use in the EHR at the George Pompidou hospital. 13.4% of the data
      elements of the eCRFs were found to be represented in EHR templates and were
      therefore candidate for pre-population. During the execution phase of the
      clinical study, the semantic mapping architecture enabled data persisted in the
      EHR context as part of clinical care to be used to pre-populate eCRFS for use
      without secondary data entry. To ensure that the pre-populated data is viable for
      use in the clinical research context, all pre-populated eCRF data needs to be
      first approved by a trial investigator prior to being persisted in a research
      data store within a CDMS. CONCLUSION: Single-source data entry in the clinical
      care context for use in the clinical research context - a process enabled through
      the use of the EHR as single point of data entry, can - if demonstrated to be a
      viable strategy - not only significantly reduce data collection efforts while
      simultaneously increasing data collection accuracy secondary to elimination of
      transcription or double-entry errors between the two contexts but also ensure
      that all the clinical data for a given patient, irrespective of the data
      collection context, are available in the EHR for decision support and treatment
      planning. The RE-USE approach used mapping algorithms to identify semantic
      coherence between clinical care and clinical research data elements and pre
      populate eCRFs. The RE-USE project utilized SNOMED International v.3.5 as its
      "pivot reference terminology" to support EHR-to-eCRF mapping, a decision that
      likely enhanced the "recall" of the mapping algorithms. The RE-USE results
      demonstrate the difficult challenges involved in semantic integration between the
      clinical care and clinical research contexts.

PMID- 21888990
TI  - Expansion of the modified Zelen's approach randomization and dynamic
      randomization with partial block supplies at the centers to unequal allocation.
AB  - Modified Zelen's approach is a randomization technique useful in multi-center
      trials where balance in treatment assignments within a center is desired. It has
      great balancing properties in a study with equal allocation to several treatment
      arms. This technique can also be used in studies with unequal allocation, where
      it would provide an allocation ratio close to the targeted one within centers as
      well as across centers. However, the implementation of the modified Zelen's
      approach for unequal allocation involves more than just imposing a constraint on
      within-center imbalance in treatment assignments, as is the case with equal
      allocation. Failure to account for this might provide a potential for accidental
      bias and (even in a double-blind study) selection and evaluation bias. The naive
      expansion of the modified Zelen's approach to unequal allocation can also lead to
      a shift in the re-randomization distribution of the between-group difference in
      treatment means. This paper will explain why and will offer an easy way to expand
      the modified Zelen's approach to unequal allocation that allows one to avoid
      these issues. The expansion to unequal allocation of another very useful in multi
      center trials technique where partial blocks of supplies are sent to the centers
      will be offered.

PMID- 21888991
TI  - Genetic comparison among dolphin morbillivirus in the 1990-1992 and 2006-2008
      Mediterranean outbreaks.
AB  - In 1990, dolphin morbillivirus (DMV) killed thousands of striped dolphins in the
      Mediterranean. Subsequently, the prevalence of the infection declined in this
      species. In 2006-2008, the virus killed not only numerous striped dolphins but
      also long-finned pilot whales. All partial sequences of the phosphoprotein and
      nucleoprotein genes obtained thus far from different host species during the 2006
      2008 outbreak show 100% identity, suggesting that a single virus was involved,
      and these sequences are nearly identical to the 1990 Spanish strain. Here our
      first objective was to determine the sequence identity between the morbillivirus
      from the 2006-2008 outbreak and the 1990 Spanish strain by sequencing more
      extensive genomic regions of strains from one pilot whale and one striped dolphin
      stranded in 2007. The second objective was to investigate the relationship
      between the 1990 and 2007 strains by constructing a phylogenetic tree based on
      the phosphoprotein gene to compare several Cetacean morbilliviruses, and another
      tree based on the nearly complete genomes of Mediterranean DMV. The third
      objective was to identify the most variable regions in the DMV genomes. Results
      showed that the two 2007 Spanish strains were 99.9% identical over 9050 bp and
      should be considered the same virus, and that this virus is 99.3-99.4% similar to
      the 1990 Spanish strain. The phylogenetic trees, together with the common
      geographical area for the two outbreaks, suggest that the 2007 DMV strains
      evolved from the 1990 DMV strain. Pilot whales do not seem to have been exposed
      or infected during the 1990-1992 epidemic, since these populations appeared to be
      immunologically naive in 2006-2008. Our results suggest that the virus may have
      evolved in striped dolphin populations prior to the 2006-2008 outbreak, after
      which it entered the long-finned pilot whale, perhaps aided by an alanine to
      valine mutation in the N-terminal domain of the fusion protein.

PMID- 21888993
TI  - Effects of dead space loading on neuro-muscular and neuro-ventilatory coupling of
      the respiratory system during exercise in healthy adults: implications for
      dyspnea and exercise tolerance.
AB  - We examined the effects of dead space loading (DSL) on ventilation (VE), neural
      respiratory drive (EMGdi%max, diaphragm EMG expressed as a % of maximal EMGdi),
      contractile respiratory muscle effort (Pes,tidal%P(Imax), tidal esophageal
      pressure swing expressed as a % of maximal inspiratory Pes) and exertional
      dyspnea intensity ratings in 11 healthy adults with normal spirometry. Subjects
      completed, in random order, symptom-limited incremental cycle exercise tests
      under control (CTRL) and DSL (500 ml) conditions. Compared with CTRL, DSL
      decreased exercise tolerance by 20-25%; increased exertional dyspnea intensity
      ratings in direct proportion to concurrent increases in EMGdi%max,
      Pes,tidal%P(Imax) and VE; and had little/no effect on the inter-relationships
      between EMGdi%max, Pes,tidal%P(Imax) and VE during exercise. In conclusion, DSL
      was associated with an earlier onset of intolerable dyspnea; however, neuro
      muscular and neuro-ventilatory coupling of the respiratory system remained
      relatively preserved during exercise in the presence of an increased external
      dead space. Under these circumstances, DSL-induced increases in exertional
      dyspnea intensity ratings reflected, at least in part, the awareness of increased
      neural respiratory drive, contractile respiratory muscle effort and ventilatory
      output.

PMID- 21888992
TI  - Population structure of hyperinvasive serotype 12F, clonal complex 218
      Streptococcus pneumoniae revealed by multilocus boxB sequence typing.
AB  - At least four outbreaks of invasive disease caused by serotype 12F, clonal
      complex 218 Streptococcus pneumoniae have occurred in the United States over the
      past two decades. We studied the population structure of this clonal complex
      using a sample of 203 outbreak and surveillance isolates that were collected over
      22 years from 34 US states and eight other countries. Conventional multilocus
      sequence typing identified five types and distinguished a single outbreak from
      the others. To improve typing resolution, multilocus boxB sequence typing (MLBT)
      was developed from 10 variable boxB minisatellite loci. MLBT identified 86 types
      and distinguished between each of the four outbreaks. Diversity across boxB loci
      tended to be positively correlated with repeat array size and, overall, best fit
      the infinite alleles mutation model. Multilocus linkage disequilibrium was
      strong, but pairwise disequilibrium decreased with the physical distance between
      loci and was strongest in one large region of the chromosome, indicating recent
      recombinations. Two major clusters were identified in the sample, and they were
      differentiated geographically, as western and more easterly US clusters, and
      temporally, as clusters that predominated before and after the licensure of
      pneumococcal conjugate vaccines. The diversity and linkage disequilibrium within
      these two clusters also differed, suggesting different population dynamics. MLBT
      revealed hidden aspects of the population structure of these hyperinvasive
      pneumococci, and it may provide a useful adjunct tool for outbreak
      investigations, surveillance, and population genetics studies of other
      pneumococcal clonal complexes.

PMID- 21888994
TI  - Bone integration capability of alkali- and heat-treated nanobimorphic Ti-15Mo-5Zr
      3Al.
AB  - The role of nanofeatured titanium surfaces in a number of aspects of in vivo bone
      implant integration, and, in particular, their potential advantages over
      microfeatured titanium surfaces, as well as their specific contribution to
      osteoconductivity, is largely unknown. This study reports the creation of a
      unique nanobimorphic titanium surface comprised of nanotrabecular and nanotuft
      like structures and determines how the addition of this nanofeature to a
      microroughened surface affects bone-implant integration. Machined surfaces
      without microroughness, sandblasted microroughened surfaces, and micro-nano
      hybrid surfaces created by sandblasting and alkali and heat treatment of Ti-15Mo
      5Zr-3Al alloy were subjected to biomechanical, interfacial and histological
      analyses in a rat model. The presence of microroughness enabled accelerated
      establishment of biomechanical implant fixation in the early stages of healing
      compared to the non-microroughened surfaces; however, it did not increase the
      implant fixation at the late stages of healing. The addition of nanobimorphic
      features to the microroughened surfaces further increased the implant fixation by
      as much as 60-100% over the healing time. Bone area within 50 MUm of the implant
      surface, but not beyond this distance, was significantly increased by the
      presence of nanobimorphic features. Although the percentage of bone-implant
      contact was also significantly increased by the addition of nanobimorphic
      features, the greatest improvement was found in the soft tissue intervention
      between the bone and the implant, which was reduced from >30% to <5%. Mineralized
      tissue densely deposited with calcium-binding globular proteins was observed in
      an extensive area of nanobimorphic surfaces after biomechanical testing. This
      study clearly demonstrates the nanofeature-enhanced osteoconductivity of titanium
      by an alkali- and heat-treated nanobimorphic surface compared to that by
      microfeatured surfaces, which results not only in an acceleration but also an
      improvement of bone-implant integration. The identified biological parameters
      that successfully detect the advantages of nanofeatures over microfeatures will
      be useful in evaluating new implant surfaces in future studies.

PMID- 21888995
TI  - Progressive hearing loss associated with a unique cervical node due to a
      homozygous SLC29A3 mutation: a very mild phenotype.
AB  - In 2008, SLC29A3 has been implicated in a syndromic form of genodermatosis: H
      syndrome. The major features encountered in H syndrome are Hearing loss,
      Hyperglycaemia, Heart anomalies, Hypertrichosis, Hyperpigmentation, Hepatomegaly
      and Hypogonadism. More recently, SLC29A3 mutations have been described in
      families presenting syndromes associating generalized histiocytosis to systemic
      progressive features: severe camptodactyly, hearing loss, hypogonadism,
      hepatomegaly, heart defects and skin hyperpigmentation. We have identified a
      homozygous missense SLC29A3 mutation in a patient presenting with only a
      progressive sensorineural hearing impairment and a single cervical node (Rosai
      Dorfman). SLC29A3 mutations appear to be involved in a large phenotypic continuum
      which should prompt physicians to study this gene even in mild clinical
      presentations.

PMID- 21888996
TI  - Overexpression and characterization of a novel transgalactosylic and hydrolytic
      beta-galactosidase from a human isolate Bifidobacterium breve B24.
AB  - After the complete gene of a beta-galactosidase from human isolate
      Bifidobacterium breve B24 was isolated by PCR and overexpressed in E. coli, the
      recombinant beta-galactosidase was purified to homogeneity and characterized for
      the glycoside transferase (GT) and glycoside hydrolase (GH) activities on
      lactose. One complete ORF encoding 691 amino acids (2,076 bp) was the structural
      gene, LacA (galA) of the beta-gal gene. The recombinant enzyme shown by activity
      staining and gel-filtration chromatography was composed of a homodimer of 75 kDa
      with a total molecular mass of 150 kDa. The K(m) value for lactose (95.58 mM) was
      52.5-fold higher than the corresponding K(m) values for the synthetic substrate
      ONPG (1.82 mM). This enzyme with the optimum of pH 7.0 and 45 degrees C could
      synthesize approximately 42.00% of GOS from 1M of lactose. About 97.00% of
      lactose in milk was also quickly hydrolyzed by this enzyme (50 units) at 45
      degrees C for 5h to produce 46.30% of glucose, 46.60% of galactose and 7.10% of
      GOS. The results suggest that this recombinant beta-galactosidase derived from a
      human isolate B. breve B24 may be suitable for both the hydrolysis and synthesis
      of galacto-oligosaccharides (GOS) in milk and lactose processing.

PMID- 21888997
TI  - RT-SVR+q: a strategy for post-Mascot analysis using retention time and q value
      metric to improve peptide and protein identifications.
AB  - Shotgun proteomics commonly utilizes database search like Mascot to identify
      proteins from tandem MS/MS spectra. False discovery rate (FDR) is often used to
      assess the confidence of peptide identifications. However, a widely accepted FDR
      of 1% sacrifices the sensitivity of peptide identification while improving the
      accuracy. This article details a machine learning approach combining retention
      time based support vector regressor (RT-SVR) with q value based statistical
      analysis to improve peptide and protein identifications with high sensitivity and
      accuracy. The use of confident peptide identifications as training examples and
      careful feature selection ensures high R values (>0.900) for all models. The
      application of RT-SVR model on Mascot results (p=0.10) increases the sensitivity
      of peptide identifications. q Value, as a function of deviation between predicted
      and experimental RTs (DeltaRT), is used to assess the significance of peptide
      identifications. We demonstrate that the peptide and protein identifications
      increase by up to 89.4% and 83.5%, respectively, for a specified q value of 0.01
      when applying the method to proteomic analysis of the natural killer leukemia
      cell line (NKL). This study establishes an effective methodology and provides a
      platform for profiling confident proteomes in more relevant species as well as a
      future investigation of accurate protein quantification.

PMID- 21888999
TI  - Restoration of the anterior maxilla after thermal trauma as a sequela to post
      removal: a clinical report.
AB  - Removing posts from endodontically treated teeth without considering the effects
      of heat trauma can have adverse consequences for the tissues surrounding the
      roots of the associated teeth. Ultrasonic instrumentation has been widely used as
      a more conservative approach than other methods of removing posts without
      untoward sequelae. However, copious irrigation must be used to prevent elevated
      temperatures caused by ultrasonic energy. This clinical report presents the
      consequences of post removal in 2 maxillary incisors with ultrasonic
      instrumentation without sufficient regard to root overheating. Necrosis of the
      surrounding tissues was observed after 2 weeks. The functional and esthetic
      reconstruction of the area affected by the heat trauma is described.

PMID- 21889000
TI  - Complete and partial contour zirconia designs for crowns and fixed dental
      prostheses: a clinical report.
AB  - Since the introduction of milled zirconia copings for ceramic crowns, a variety
      of techniques have been introduced to reduce the incidence of chipping or
      fracturing of the porcelain veneer. These include methods of improving the
      interface between the coping and the veneer, reducing thermal incompatibility
      between the two, and optimizing the coping design to minimize tensile loading on
      the porcelain. Another method of reducing porcelain chipping and fracture is to
      limit or eliminate the porcelain coverage of zirconia copings and frameworks.
      Even though patients often demand tooth colored or nonmetallic restorations, they
      tend to be less concerned with the optimal esthetics of their posterior teeth.
      This article describes 4 representative clinical situations where efforts were
      made to minimize or eliminate porcelain coverage on posterior zirconia crowns and
      a fixed dental prosthesis, while still achieving acceptable, but not optimal,
      esthetics.

PMID- 21888998
TI  - Chromatin-mediated Candida albicans virulence.
AB  - Candida albicans is the most prevalent human fungal pathogen. To successfully
      propagate an infection, this organism relies on the ability to change morphology,
      express virulence-associated genes and resist DNA damage caused by the host
      immune system. Many of these events involve chromatin alterations that are
      crucial for virulence. This review will focus on the studies that have been
      conducted on how chromatin function affects pathogenicity of C. albicans and
      other fungi. This article is part of a Special Issue entitled: Histone chaperones
      and Chromatin assembly.

PMID- 21889001
TI  - An interdisciplinary treatment to manage pathologic tooth migration: a clinical
      report.
AB  - Pathologic tooth migration (PTM) is a common symptom of periodontal disease and a
      motivation for the patient to seek dental therapy. The primary factors causing
      PTM are periodontitis and occlusal trauma. Comprehensive treatment for managing a
      moderate degree of PTM, including periodontal, orthodontic and prosthodontic
      treatment is described. Increasing the occlusal vertical dimension (OVD) with
      provisional restorations was attempted to create space for retracting maxillary
      flared teeth. Retraction and intrusion of maxillary flared incisors were achieved
      by a sectional orthodontic appliance. Splinted crowns from maxillary right
      lateral incisor to left lateral incisor were fabricated and connected to
      posterior prostheses by means of attachments to prevent relapse and to provide
      long-term stability.

PMID- 21889002
TI  - Effect of repeated screw joint closing and opening cycles on implant prosthetic
      screw reverse torque and implant and screw thread morphology.
AB  - STATEMENT OF PROBLEM: Clinicians must know if a new screw can predictably
      increase reverse torque after multiple screw insertion cycles. PURPOSE: The
      purpose of this study was (1) to compare the effect of multiple implant
      prosthetic screw insertion and removal cycles on reverse torque, (2) to determine
      whether a new screw, after multiple screw insertion cycles, affects reverse
      torque, and (3) to assess implant and prosthetic screw thread surface morphology
      with scanning electron microscopy (SEM). MATERIAL AND METHODS: One primary screw
      was paired with an implant (MT Osseospeed) and inserted to 25 Ncm torque 9, 19,
      29, or 39 times (n=10). Primary screw reverse torque values were recorded after
      each insertion. A second, reference screw was then paired with each implant for a
      final screw insertion, and reverse torque was measured. Maximum, minimum, median,
      and mean values (P(max), P(min), P(median), and P(mean)) were identified for
      primary screws. A 1-way ANOVA and Tukey HSD post hoc analysis assessed the
      influence of multiple screw insertion cycles on P(max), P(min), P(median), and
      P(mean) values (alpha=.05). Confidence intervals were used to test differences
      between reference (REF) screw data and corresponding DMAX and DMIN (DMAX=P(max)
      REF; DMIN=P(min)-REF). The surface topography of an unused implant and screw and
      of 1 implant and screw from each group was evaluated with SEM. RESULTS: Pairwise
      comparisons showed that 9 or fewer insertion cycles resulted in significantly
      greater mean reverse torque (20.9 +/- 0.5 Ncm; P<.01). After 19, 29, or 39
      cycles, the second, reference screw achieved significantly greater reverse torque
      than the minimum recorded values (P<.05). Implant thread surface morphology
      changes occurred primarily during the first 10 insertions. CONCLUSIONS: After 10
      screw insertion cycles, a new prosthetic screw should be used with the implant
      system tested to maximize screw reverse torque and maintain preload when an
      abutment is definitively placed.

PMID- 21889003
TI  - Microstructure, elemental composition, hardness and crystal structure study of
      the interface between a noble implant component and cast noble alloys.
AB  - STATEMENT OF PROBLEM: Casting a high-gold alloy to a wrought prefabricated noble
      implant-component increases the cost of an implant. Selecting a less expensive
      noble alloy would decrease implant treatment costs. PURPOSE: The purpose of this
      study was to investigate the interfacial regions of a representative noble
      implant component and cast noble dental alloys and to evaluate the effects of
      porcelain firing cycles on the interface. MATERIAL AND METHODS: Six
      representative alloys (n=3) were cast to gold implant abutments (ComOcta).
      Scanning electron microscopy (SEM) was used to characterize microstructures.
      Compositions of interfacial regions and bulk alloys were obtained by energy
      dispersive spectroscopy. Vickers hardness was also measured across the interface.
      By using Micro-X-ray diffraction, the phases were evaluated at 7 points
      perpendicular to the interface. The effects of porcelain firing cycles on
      microstructures, diffusion, hardness, and phases were also evaluated. For
      statistical evaluation of diffusion length and hardness, a 3-way repeated
      measures ANOVA was used. Pairwise comparisons of interest were conducted with
      Tukey pairwise comparisons or, when a significant interaction was found,
      Bonferroni-adjusted t-tests (overall alpha=.05). RESULTS: Microstructures of bulk
      alloys were predominantly maintained to a well-defined boundary for both as-cast
      and heat-treated conditions. An interaction band, 5-6 MUm wide, was observed. The
      alloy grain size at the interface and the interaction band width increased after
      simulated porcelain firing. The extent of elemental diffusion from the interface
      was about 30 MUm and not affected by simulated porcelain firing. Differences in
      Vickers hardness for the alloys were consistent with their compositions. Micro
      XRD patterns indicated that substantial amounts of new phases had not formed at
      the interfacial regions. CONCLUSIONS: Less expensive noble alternatives to high
      gold alloys provided comparable metallurgical compatibility with the noble
      implant component.

PMID- 21889004
TI  - Effect of substrate shades on the color of ceramic laminate veneers.
AB  - STATEMENT OF PROBLEM: Ceramic laminate veneers are generally fabricated with
      varying thicknesses ranging from 0.3 to 1 mm, depending on the need to mask
      discolored teeth or slightly correct the contour of malpositioned teeth. Clinical
      color reproduction poses a challenge because of color interaction with the
      underlying substrate, whether tooth structure or esthetic restorative material.
      PURPOSE: The purpose of this in vitro investigation was to measure the effect of
      color change resulting from applying 2 shades of ceramic material, translucent
      (T1) and opaque (O2), to 2 shades of composite resin substrate material, light
      (A3) and dark (C4), on the overall color of ceramic laminates. MATERIAL AND
      METHODS: Forty disks were fabricated. Twenty disks (15 * 0.5 mm) were cut from
      pressed ceramic, 10 disks for each shade (translucent and opaque). Additionally,
      20 disks (15 * 4.0 mm) were fabricated from light-polymerized composite resin
      material, 10 disks for each shade (light and dark). The ceramic disks were bonded
      to the composite resin disks with clear resin cement. The specimen combinations
      were divided into 4 groups (n=5). Color measurements were done with a colorimeter
      (Minolta Chroma Meter CR-200b) configured with diffuse illumination/0-degree
      viewing geometry. Mean CIE lightness (L*), chroma (C*(ab)), and hue angle (h(ab))
      values were obtained. A 2-way analysis of variance (ANOVA) was used to compare
      the means and standard deviations between the different color combinations
      (alpha=.05), followed by Tukey's HSD post hoc test for significant interactions.
      RESULTS: The 2-way ANOVA showed significant differences (P<.001) in L*, C*(ab),
      and h(ab) for a change in the composite resin substrate, regardless of the
      ceramic material shade. There was significant color change from dark to light
      substrate (P=.044). The mean h(ab) (SD) of dark substrate/opaque veneer was 89.62
      (1.5), while the mean h(ab) of light substrate/translucent veneer was 81.23
      (1.7). CONCLUSIONS: Within the limitations of this study, the selected color of a
      0.5 mm ceramic laminate veneer was significantly affected by the change in color
      of the supporting substrate.

PMID- 21889005
TI  - The impact of post preparation on the residual dentin thickness of maxillary
      molars.
AB  - STATEMENT OF PROBLEM: The oval-shaped palatal roots of maxillary molars usually
      have smaller cross-sectional diameter in the buccolingual direction. However, the
      effect of parallel-sided post preparation on the remaining dentin thickness of
      root canal walls is unknown. PURPOSE: The purpose of this study was to
      investigate, in vitro, the residual dentin thickness (RDT) of palatal roots in
      maxillary molars after various intracanal procedures for post placement, and to
      determine the risk of root canal perforation or weakening on different root canal
      walls at 2 levels, coronal and apical. MATERIAL AND METHODS: Fifteen extracted
      first maxillary molars exhibiting radiographic mesiodistal root canal widths
      ranging from 3.8 to 4.2 mm, measured at 5 mm from the apex, were selected from a
      pool of teeth. The teeth were horizontally sectioned at 2 levels, coronal and
      apical, after being embedded in acrylic resin with the aid of a metal index,
      allowing identical repositioning of the sectioned parts throughout the study.
      Each sectioned surface was photographed with a digital camera coupled to a
      microscope. The palatal roots were subsequently prepared for post placement as
      follows: endodontic preparation up to file K50, Largo 3 and 4 drills, and
      ParaPost 4.5 and 5.0. Cross-sections were rephotographed after each step. Image J
      software was used to measure the RDT of each root wall at both levels, and data
      were further analyzed with a 3-way ANOVA/General Linear Model (GLM) for repeated
      measures. The post-hoc Tukey's range test was used to calculate differences in
      RDT among the 4 root walls at each root level (alpha=.05). RESULTS: A significant
      difference was observed among the intracanal procedures (P<.001). At the apical
      level, RDT was significantly lower after ParaPost preparation than at the coronal
      level (P=.009). Buccal and palatal walls displayed significantly lower RDT than
      the mesial and distal walls at both levels (P=.004). CONCLUSIONS: Intracanal
      preparation up to ParaPost 5.0 increased the risk of perforation or weakening of
      the buccal and palatal walls, especially at the apical level.

PMID- 21889006
TI  - Marginal accuracy and internal fit of machine-milled and cast titanium crowns.
AB  - STATEMENT OF PROBLEM: Titanium is an alternative tooth restorative material
      because of a its biocompatibility and mechanical properties. However, there is
      little information on the marginal accuracy of a complete titanium crown with
      different margin configurations. PURPOSE: This study examined the effect of
      fabrication method and margin configuration on the marginal and internal fit of
      complete titanium crowns. MATERIAL AND METHODS: An acrylic resin maxillary first
      molar was prepared with shoulder (buccal), chamfer (palatal), and knife edge
      (proximal) margin configurations. Forty crowns were produced and then divided
      into 2 groups according to the manufacturing method (casting method or CAD/CAM
      technique) (n=20). Each crown was luted to the original stone die with zinc
      phosphate cement. The margin of the crown, center point of the axial wall, and
      occlusal area were measured with a 3-dimensional measuring microscope. An
      independent t-test (internal gap) and repeated measures 2-way ANOVA (marginal
      gap) were used for statistical analysis (alpha=.05). RESULTS: The mean marginal
      gap of the cast group was significantly smaller than that of the CAD/CAM group
      (P<.001). The margin configuration affected the measured marginal discrepancy
      (P<.001). In both groups, the mean marginal gap of the chamfer and shoulder
      margin was significantly smaller than that of the knife-edge margin (P<.001).
      CONCLUSIONS: Castings-produced titanium crowns with a better marginal fit than
      the CAD/CAM technique. The knife-edge margin exhibited the greatest marginal
      discrepancy.

PMID- 21889007
TI  - An alternative multiple pontic design for a fixed implant-supported prosthesis.
AB  - In situations of moderate residual ridge resorption where multiple tooth
      replacement is needed, and where the patient desires a fixed implant-supported
      restoration, it is challenging to design a pontic-tissue interface. The
      semiconvex multiple pontic design described in this article, with its mucosal
      contact exerted with moderate pressure, is proposed to circumvent the problems
      encountered with the plaque accumulation, maintenance conditions, phonetics, and
      compromised esthetics frequently encountered in these patients. The use of a
      screw-retained, implant-supported restoration is also emphasized to allow for
      sufficient tissue contact during placement of the prosthesis and for prosthesis
      retrievability for maintenance or technical reasons.

PMID- 21889008
TI  - A technique for making impressions of deeply placed implants.

PMID- 21889009
TI  - Pediatric thoracic imaging.

PMID- 21889010
TI  - Fetal chest ultrasound and magnetic resonance imaging: recent advances and
      current clinical applications.
AB  - Advances in high-resolution prenatal ultrasound and fetal magnetic resonance (MR)
      imaging have changed the practice of obstetrics by allowing better visualization
      of intrathoracic and neck structures and better estimation of lung volumes. More
      accurate prenatal diagnosis has increased options for pregnancy management and
      treatment, delivery planning, and postnatal care. Anyone who is interested in the
      fascinating field of fetology should become familiar with the current state of
      fetal imaging of the chest as well as potential advances in technology and
      research.

PMID- 21889011
TI  - Chest sonography in children: current indications, techniques, and imaging
      findings.
AB  - Ultrasound of the thorax is particularly rewarding in children, because their
      unique thoracic anatomy provides many available acoustic windows into the chest.
      Newer ultrasound techniques can allow better understanding of lung disease. With
      minimum effort and creativity, chest ultrasound can provide important clinical
      information without radiation exposure or sedation sometimes required for
      computed tomography and magnetic resonance imaging.

PMID- 21889012
TI  - Contemporary perspectives on pediatric diffuse lung disease.
AB  - It is much more challenging in children than in adults to obtain computed
      tomography images of the lung parenchyma at optimal lung volumes without motion
      artifact. Some of the more common forms of diffuse lung disease in adults rarely
      occur in children, and several forms of diffuse lung disease are unique to
      children. Recognition of these differences has led to the development of a new
      classification scheme for pediatric diffuse lung disease. Knowledge of this
      classification and recognition of characteristic imaging findings of specific
      disorders will lead to accurate diagnosis and guide appropriate treatment of
      children with diffuse lung disease.

PMID- 21889013
TI  - Multidetector computed tomography of pediatric large airway diseases: state-of
      the-art.
AB  - Advances in multidetector computed tomography (MDCT) technology have given rise
      to improvements in the noninvasive and comprehensive assessment of the large
      airways in pediatric patients. Superb two-dimensional and three-dimensional
      reconstruction MDCT images have revolutionized the display of large airways and
      enhanced the ability to diagnose large airway diseases in children. The 320-MDCT
      scanner, which provides combined detailed anatomic and dynamic functional
      information assessment of the large airways, is promising for the assessment of
      dynamic large airway disease such as tracheobronchomalacia. This article
      discusses imaging techniques and clinical applications of MDCT for assessing
      large airway diseases in pediatric patients.

PMID- 21889014
TI  - Pneumonia in normal and immunocompromised children: an overview and update.
AB  - Pneumonia is an infection of the lung parenchyma caused by a wide variety of
      organisms in pediatric patients. The role of imaging is to detect the presence of
      pneumonia, and determine its location and extent, exclude other thoracic causes
      of respiratory symptoms, and show complications such as effusion/empyema and
      suppurative lung changes. The overarching goal of this article is to review
      cause, role of imaging, imaging techniques, and the spectrum of acute and chronic
      pneumonias in children. Pneumonia in the neonate and immunocompromised host is
      also discussed.

PMID- 21889015
TI  - Congenital pulmonary malformations in pediatric patients: review and update on
      etiology, classification, and imaging findings.
AB  - Congenital pulmonary malformations represent a heterogeneous group of
      developmental disorders affecting the lung parenchyma, the arterial supply to the
      lung, and the lung's venous drainage. In both asymptomatic and symptomatic
      pediatric patients with congenital pulmonary malformations, the diagnosis of such
      malformations usually requires imaging evaluation, particularly in cases of
      surgical lesions for preoperative assessment. The goal of this article is to
      review the current imaging techniques for evaluating congenital pulmonary
      malformations and their characteristic imaging findings, which can allow
      differentiation among various congenital pulmonary malformations in pediatric
      patients.

PMID- 21889016
TI  - Chest trauma in children: current imaging guidelines and techniques.
AB  - Given the heterogeneous nature of pediatric chest trauma, the optimal imaging
      approach is tailored to the specific patient. Chest radiography remains the most
      important imaging modality for initial triage. The decision to perform a chest
      computed tomography scan should be based on the nature of the trauma, the child's
      clinical condition, and the initial radiographic findings, taking the age-related
      pretest probabilities of serious injury into account. The principles of as low as
      reasonably achievable and Image Gently should be followed. The epidemiology and
      pathophysiology, imaging techniques, characteristic findings, and evidence-based
      algorithms for pediatric chest trauma are discussed.

PMID- 21889017
TI  - Congenital thoracic vascular anomalies: evaluation with state-of-the-art MR
      imaging and MDCT.
AB  - Congenital thoracic vascular anomalies include embryologic developmental
      disorders of the thoracic aorta, aortic arch branch arteries, pulmonary arteries,
      thoracic systemic veins, and pulmonary veins. Diagnostic evaluation of these
      anomalies in pediatric patients has evolved with innovations in diagnostic
      imaging technology. State-of-the-art magnetic resonance (MR) imaging, MR
      angiography multidetector-row computed tomographic (MDCT) angiography, and
      advanced postprocessing visualization techniques offer accurate and reliable high
      resolution two-dimensional and three-dimensional noninvasive anatomic displays
      for interpretation and clinical management of congenital thoracic vascular
      anomalies. This article reviews vascular MR imaging, MR angiography, MDCT
      angiography, and advanced visualization techniques and applications for the
      assessment of congenital thoracic vascular anomalies, emphasizing clinical
      embryology and the characteristic imaging findings.

PMID- 21889018
TI  - Cardiac MDCT in children: CT technology overview and interpretation.
AB  - Cardiac multidetector computed tomography (MDCT) for congenital heart disease is
      a useful, rapid, and noninvasive imaging technique bridging the gaps between
      echocardiography, cardiac catheterization, and cardiac MRI. Fast scan speed and
      greater anatomic coverage, combined with flexible ECG-synchronized scans and a
      low radiation dose, are critical for improving the image quality of cardiac MDCT
      and minimizing patient risk. Current MDCT techniques can accurately evaluate
      extracardiac great vessels, lungs, and airways, as well as coronary arteries and
      intracardiac structures. Radiologists who perform cardiac MDCT in children should
      be familiarized with optimal cardiac computed tomography (CT) scan techniques and
      characteristic cardiac CT scan imaging findings.

PMID- 21889019
TI  - Preoperative and postoperative MR evaluation of congenital heart disease in
      children.
AB  - Cardiovascular magnetic resonance imaging (CMR) plays an important role in the
      preoperative and postoperative evaluation of congenital heart disease with newer
      techniques enabling faster and more comprehensive evaluation of the pediatric
      patient. This article reviews the clinical applications of CMR before and after
      surgery in the most common congenital heart anomalies in pediatric patients.

PMID- 21889020
TI  - Nuclear medicine and molecular imaging of the pediatric chest: current practical
      imaging assessment.
AB  - In the chest, the indications for nuclear medicine studies are broader and more
      varied in children than in adults. In children, nuclear medicine studies are used
      to evaluate congenital and developmental disorders of the chest, as well as
      diseases more typical of adults. In the chest, pediatric nuclear medicine uses
      the same radiopharmaceuticals and imaging techniques as used in adults to
      evaluate cardiac and pulmonary disease, aerodigestive disorders, and pediatric
      malignancies. The introduction of PET (mostly using (18)F-FDG) has transformed
      pediatric nuclear oncology, particular for imaging malignancies in the chest.

PMID- 21889022
TI  - Gastric surgery. Foreword.

PMID- 21889021
TI  - Radiation, thoracic imaging, and children: radiation safety.
AB  - The chest is the most frequently evaluated region of the body in children. The
      majority of thoracic diagnostic imaging, namely "conventional" radiography (film
      screen, computed radiography and direct/digital radiography), fluoroscopy and
      angiography, and computed tomography, depends on ionizing radiation. Since
      errors, oversights, and inattention to radiation exposure continue to be
      extremely visible issue for radiology in the public eye it is incumbent on the
      imaging community to maximize the yield and minimize both the real and potential
      radiation risks with diagnostic imaging. Technical (e.g. equipment and technique)
      strategies can reduce exposure risk and improve study quality, but these must be
      matched with efforts to optimize appropriate utilization for safe and effective
      healthcare in thoracic imaging in children. To these ends, material in this
      chapter will review practice patterns, dose measures and modality doses,
      radiation biology and risks, and radiation risk reduction strategies for thoracic
      imaging in children.

PMID- 21889023
TI  - Gastric surgery. Preface.

PMID- 21889024
TI  - Gastric acid and digestive physiology.
AB  - The primary function of the stomach is to prepare food for digestion and
      absorption by the intestine. Acid production is the unique and central component
      of the stomach's contribution to the digestive process. Acid bathes the food
      bolus while stored in the stomach, facilitating digestion. An intact defense
      against mucosal damage by the stomach's acid is essential to avoid ulceration.
      This article focuses on the physiology of gastric acid production, the stomach's
      defense mechanisms against acid injury, and the most common challenges to the
      gastric defenses. A brief description of the stomach's nonacid digestive
      capabilities is included.

PMID- 21889025
TI  - Gastric motility physiology and surgical intervention.
AB  - Disordered gastric motility represents a spectrum of dysfunction ranging from
      delayed gastric emptying to abnormally rapid gastric transit, commonly referred
      to as the "dumping syndrome." Both extremes of gastric motility disorders can
      arise from similar pathologic processes, and produce remarkably identical
      symptoms. This fact underscores the need to attain a precise diagnosis to ensure
      the institution of optimal therapy. Disordered gastric motility is primarily
      managed with dietary modification followed by pharmacotherapy, as traditional
      surgical interventions tend to be fraught with complications. However, continued
      improvements in minimally invasive diagnostic and therapeutic modalities promise
      novel options for earlier and more effective treatment.

PMID- 21889026
TI  - Emergency ulcer surgery.
AB  - The rate of elective surgery for peptic ulcer disease has been declining steadily
      over the past 3 decades. During this same period, the rate of emergency ulcer
      surgery rose by 44%. This means that the gastrointestinal surgeon is likely to be
      called on to manage the emergent complications of peptic ulcer disease without
      substantial experience in elective peptic ulcer disease surgery. The goal of this
      review is to familiarize surgeons with our evolving understanding of the
      pathogenesis, epidemiology, presentation, and management of peptic ulcer disease
      in the emergency setting, with a focus on peptic ulcer disease-associated
      bleeding and perforation.

PMID- 21889027
TI  - Gastroesophageal reflux disease.
AB  - Millions of Americans are affected by gastroesophageal reflux disease (GERD) in
      many different ways. The magnitude of the problem of GERD was brought to light by
      the ambulatory pH test, the introduction of minimally invasive surgery, and the
      advent of the many medications that are effective in acid suppression. Patients
      with GERD suffer from various consequences associated with the disease. However,
      interventions beyond medical therapy, such as laparoscopic fundoplication,
      provide satisfactory outcomes and definitive relief of acid reflux.

PMID- 21889028
TI  - Achalasia.
AB  - This article reviews the diagnosis and treatment of achalasia, a rare esophageal
      motility disorder characterized by absent peristalsis and failure of the lower
      esophageal sphincter (LES) to relax. Various treatment options including
      management with sublingual nitrates or calcium channel blockers, injection of the
      LES with botulism toxin, pneumatic dilation of the LES, and pneumatic dilation
      are discussed. Laparoscopic Heller myotomy is minimally invasive with incumbent
      low morbidity and mortality rates, and combined with a partial fundoplication is
      a durable, safe, and effective treatment option for patients with achalasia.

PMID- 21889029
TI  - Gastric adenocarcinoma surgery and adjuvant therapy.
AB  - Gastric adenocarcinoma is one of the most common causes of death worldwide.
      Surgical resection remains the mainstay of therapy, offering the only chance for
      complete cure. Resection is based on the principles of obtaining adequate
      margins, with the extent of lymphadenectomy remaining controversial. Neoadjuvant
      and adjuvant therapies are used to reduce local recurrence and improve long-term
      survival. This article reviews the literature and provides a summary of surgical
      management options and neoadjuvant/adjuvant therapies for gastric adenocarcinoma.

PMID- 21889030
TI  - Gastrointestinal stromal tumor surgery and adjuvant therapy.
AB  - Gastrointestinal stromal tumors (GIST) are a unique class of mesenchymal tumors
      identified within the past decade. Intense molecular and genetic study has been
      used to characterize these tumors and develop treatment strategies. Although the
      mainstay of treatment remains surgical resection, therapy targeted at inhibiting
      tyrosine kinases has had dramatic results. Because of the rapid accumulation of
      information about the diagnosis and treatment of these tumors, the National
      Comprehensive Cancer Network convened a GIST task force to provide updated
      recommendations in 2010. As understanding of these tumors advances, rapid changes
      in recommendations will continue and should warrant regular updates in tumor
      management.

PMID- 21889031
TI  - Minimally invasive gastric surgery.
AB  - The most common indications for gastric resection remain benign ulcer disease and
      neoplasm. Surgery for these diseases can be performed safely with laparoscopy. As
      surgeons adhere to the original tenets of open gastric resections while
      performing laparoscopic resections, disease outcomes will remain the same with
      the improved surgical outcomes of less pain, a shorter hospital stay, and a lower
      incidence of wound complications. Laparoscopic gastric resections can be divided
      into the more straightforward wedge/tumor resections performed for submucosal
      tumors or the more formal anatomic gastric resections. This article reviews the
      tools and techniques for laparoscopic gastric resection.

PMID- 21889032
TI  - Postgastrectomy syndromes.
AB  - The first postgastrectomy syndrome was noted not long after the first gastrectomy
      was performed. The indications for gastric resection have changed dramatically
      over the past 4 decades, and the overall incidence of gastric resection has
      decreased. This article focuses on the small proportion of patients with severe,
      debilitating symptoms; these symptoms can challenge the acumen of the surgeon who
      is providing the patient's long-term follow-up and care. The article does not
      deal with the sequelae of bariatric surgery.

PMID- 21889033
TI  - Miscellaneous disorders and their management in gastric surgery: volvulus,
      carcinoid, lymphoma, gastric varices, and gastric outlet obstruction.
AB  - This article focuses on less common diseases that surgeons are called on for
      management options. Five topics-volvulus, carcinoid, lymphoma, gastric varices,
      and gastric outlet obstruction from peptic ulcer disease-are frequently used to
      evaluate surgical knowledge. Knowledge of these topics is useful for residents
      preparing for an in-training examination or board certification. Patients with
      these diseases require multidisciplinary management with oncologists and/or
      gastroenterologists, and mastery of these topics allows surgeons to effectively
      participate in the multidisciplinary care of these patients and advocate for
      surgical management when appropriate.

PMID- 21889034
TI  - International collaboration in cardiovascular nursing research.

PMID- 21889035
TI  - Recurrent coxsackie B viral myocarditis leading to progressive impairment of left
      ventricular function over 8 years.

PMID- 21889036
TI  - Hemeoxygenase-1 expression in response to arecoline-induced oxidative stress in
      human umbilical vein endothelial cells.
AB  - BACKGROUND: Arecoline, the most abundant areca alkaloid, has been reported to
      stimulate reactive oxygen species (ROS) production in several cell types.
      Overproduction of ROS has been implicated in atherogenesis. Hemeoxygenase-1 (HO
      1) has cytoprotective activities in vascular tissues. This study investigated the
      effect of arecoline on adhesion molecule expression and explored the role of HO-1
      in this process. METHODS: Human umbilical vein endothelial cells (HUVECs) were
      treated with arecoline, then ROS levels and the expression of adhesion molecules
      and HO-1 were analyzed and potential signaling pathways investigated. RESULTS:
      After 2h of arecoline treatment, ROS production was stimulated and reached a
      maximum at 12h. Expression of the adhesion molecules ICAM and VCAM was also
      induced. Glutathione pretreatment completely blocked arecoline-stimulated ROS
      production and VCAM expression, but not ICAM expression. Arecoline also induced
      HO-1 expression and this effect was partly due by ROS stimulation. Inhibition of
      c-jun N-terminal kinase (JNK) by SP600125, p38 by SB 203580, or tyrosine kinase
      by genistein reduced arecoline-induced HO-1 expression. In contrast, inhibition
      of ERK (extracellular signal-related MAP kinase) by PD98059 had no effect.
      Transfection of HUVECs with the GFP/HO-1 gene, which resulted in a 5-fold
      increase in HO-1 activity, markedly, but not completely, inhibited the decrease
      in cell viability caused by arecoline. CONCLUSIONS: This study demonstrates that,
      in HUVECs, arecoline stimulates ROS production and ICAM and VCAM expression. HO-1
      expression is also upregulated through the ROS, tyrosine kinase, and MAPK (JNK
      and p38) signaling pathways.

PMID- 21889037
TI  - (Questions)n on phloem biology. 2. Mass flow, molecular hopping, distribution
      patterns and macromolecular signalling.
AB  - This review speculates on correlations between mass flow in sieve tubes and the
      distribution of photoassimilates and macromolecular signals. Since micro- (low
      molecular compounds) and macromolecules are withdrawn from, and released into,
      the sieve-tube sap at various rates, distribution patterns of these compounds do
      not strictly obey mass-flow predictions. Due to serial release and retrieval
      transport steps executed by sieve tube plasma membranes, micromolecules are
      proposed to "hop" between sieve element/companion cell complexes and phloem
      parenchyma cells under source-limiting conditions (apoplasmic hopping). Under
      sink-limiting conditions, micromolecules escape from sieve tubes via pore
      plasmodesma units and are temporarily stored. It is speculated that
      macromolecules "hop" between sieve elements and companion cells using
      plasmodesmal trafficking mechanisms (symplasmic hopping). We explore how
      differential tagging may influence distribution patterns of macromolecules and
      how their bidirectional movement could arise. Effects of exudation techniques on
      the macromolecular composition of sieve-tube sap are discussed.

PMID- 21889038
TI  - Abiotic stress and control of grain number in cereals.
AB  - Grain number is the only yield component that is directly associated with
      increased grain yield in important cereal crops like wheat. Historical yield
      studies show that increases in grain yield are always accompanied by an increase
      in grain number. Adverse weather conditions can cause severe fluctuations in
      grain yield and substantial yield losses in cereal crops. The problem is global
      and despite its impact on world food production breeding and selection approaches
      have only met with limited success. A specific period during early reproductive
      development, the young microspore stage of pollen development, is extremely
      vulnerable to abiotic stress in self-fertilising cereals (wheat, rice, barley,
      sorghum). A better understanding of the physiological and molecular processes
      that lead to stress-induced pollen abortion may provide us with the key to
      finding solutions for maintaining grain number under abiotic stress conditions.
      Due to the complexity of the problem, stress-proofing our main cereal crops will
      be a challenging task and will require joint input from different research
      disciplines.

PMID- 21889039
TI  - Roles of Ca2+ and cyclic nucleotide gated channel in plant innate immunity.
AB  - The increase of cytosolic Ca(2+) is a vital event in plant pathogen signaling
      cascades. Molecular components linking pathogen signal perception to cytosolic
      Ca(2+) increase have not been well characterized. Plant cyclic nucleotide gated
      channels (CNGCs) play important roles in the pathogen signaling cascade, in terms
      of facilitating Ca(2+) uptake into the cytosol in response to pathogen and
      pathogen associated molecular pattern (PAMP) signals. Perception of pathogens
      leads to cyclic nucleotide production and the activation of CNGCs. The Ca(2+)
      signal is transduced through Ca(2+) sensors (Calmodulin (CaM) and CaM-like
      proteins (CMLs)), which regulates the production of nitric oxide (NO). In
      addition, roles of Ca(2+)/CaM interacting proteins such as CaM binding Protein
      (CBP) and CaM-binding transcription activators (CAMTAs)) have been recently
      identified in the plant defense signaling cascade as well. Furthermore, Ca(2+)
      dependent protein kinases (CDPKs) have been found to function as components in
      terms of transcriptional activation in response to a pathogen (PAMP) signal.
      Although evidence shows that Ca(2+) is an essential signaling component upstream
      from many vital signaling molecules (such as NO), some work also indicates that
      these downstream signaling components can also regulate Ca(2+) homeostasis. NO
      can induce cytosolic Ca(2+) increase (through activation of plasma membrane- and
      intracellular membrane-localized Ca(2+) channels) during pathogen signaling
      cascades. Thus, much work is needed to further elucidate the complexity of the
      plant pathogen signaling network in the future.

PMID- 21889040
TI  - Hypothesis/review: the structural basis of sweetness perception of sweet-tasting
      plant proteins can be deduced from sequence analysis.
AB  - Human perception of sweetness, behind the felt pleasure, is thought to play a
      role as an indicator of energy density of foods. For humans, only a small number
      of plant proteins taste sweet. As non-caloric sweeteners, these plant proteins
      have attracted attention as candidates for the control of obesity, oral health
      and diabetic management. Significant advances have been made in the
      characterization of the sweet-tasting plant proteins, as well as their binding
      interactions with the appropriate receptors. The elucidation of sweet-taste
      receptor gene sequences represents an important step towards the understanding of
      sweet taste perception. However, many questions on the molecular basis of sweet
      taste elicitation by plant proteins remain unanswered. In particular, why
      homologues of these proteins do not elicit similar responses? This question is
      discussed in this report, on the basis of available sequences and structures of
      sweet-tasting proteins, as well as of sweetness-sensing receptors. A simple
      procedure based on sequence comparisons between sweet-tasting protein and its
      homologous counterparts was proposed to identify critical residues for sweetness
      elicitation. The open question on the physiological function of sweet-tasting
      plant proteins is also considered. In particular, this review leads us to suggest
      that sweet-tasting proteins may interact with taste receptor in a serendipity
      manner.

PMID- 21889041
TI  - Why do viruses need phloem for systemic invasion of plants?
AB  - Plant viruses use sieve elements in phloem as the route of long-distance movement
      and systemic infection in plants. Plants, in turn, deploy RNA silencing, R-gene
      mediated defence and other mechanisms to prevent phloem transport of viruses.
      Cell-to-cell movement of viruses from an initially infected leaf to stem and
      other parts of the plant could be another possibility for systemic invasion, but
      it is considered to be too slow. This idea is supported by observations made on
      viruses that are deficient in phloem loading. The leaf abscission zone forming at
      the base of the petiole may constitute a barrier that prevents viral cell-to-cell
      movement. The abscission zone and protective layer are difficult to localize in
      the petiole until the leaf reaches an advanced stage of senescence. Viruses
      tagged with the green fluorescent protein are helpful for localization and study
      of the developing abscission zone.

PMID- 21889042
TI  - Timing is everything in plant development. The central role of floral repressors.
AB  - Progress in understanding the molecular basis of flowering time control has
      revealed that floral repressors play a central role in modulating the floral
      transition and are essential to prevent the precocious onset of flowering. A
      number of cellular processes including chromatin remodeling, selective protein
      degradation, and transcriptional regulation mediated by transcription factors are
      involved in repressing the initiation of flowering. Floral repressors interact at
      different levels with floral inductive pathways and prevent the premature onset
      of flowering that could impact negatively on the reproductive success of plants.
      Despite recent advances, further studies will be needed to understand how the
      interactions between floral repressors and the regulatory networks involved in
      the control of flowering time have evolved in different species. Recent data
      suggest that a diversity of regulatory proteins act as central floral repressors
      in different plants, and even in those species where regulatory modules are
      conserved new elements that modulate the function of these pathways have been
      recruited to mediate specific adaptive responses. The development of genomic
      tools and predictive models that can integrate large datasets related to the
      flowering behavior of plant species will facilitate the characterization of the
      repressor mechanisms underlying flowering responses, a trait with implications in
      the yield of crop species. In a scenario of global climate change, an in depth
      understanding of these gene circuits will be essential for the development of
      crop varieties with improved yield.

PMID- 21889043
TI  - Lignin variability in plant cell walls: contribution of new models.
AB  - Lignin is a major component of certain plant cell walls. The enzymes and
      corresponding genes associated with the metabolic pathway leading to the
      production of this complex phenolic polymer have been studied for many years now
      and are relatively well characterized. The use of genetically modified model
      plants (Arabidopsis, tobacco, poplar.) and mutants has contributed greatly to our
      current understanding of this process. The recent utilisation and/or development
      of a number of dedicated genomic and transcriptomic tools for other species opens
      new perspectives for advancing our knowledge of the biological role of this
      important polymer in less typical situations and/or species. In this context,
      studies on the formation of hypolignified G-type fibres in angiosperm tension
      wood, and the natural hypolignification of secondary cell walls in plant bast
      fibre species such as hemp (Cannabis sativa), flax (Linum usitatissimum) or ramie
      (Boehmeria nivea) are starting to provide novel information about how plants
      control secondary cell wall formation. Finally, other biologically interesting
      species for which few molecular resources currently exist could also represent
      interesting future models.

PMID- 21889044
TI  - Myo-inositol and beyond--emerging networks under stress.
AB  - Myo-inositol is a versatile compound that generates diversified derivatives upon
      phosphorylation by lipid-dependent and -independent pathways.
      Phosphatidylinositols form one such group of myo-inositol derivatives that act
      both as membrane structural lipid molecules and as signals. The significance of
      these compounds lies in their dual functions as signals as well as key
      metabolites under stress. Several stress- and non-stress related pathways
      regulated by phosphatidylinositol isoforms and associated enzymes, kinases and
      phosphatases, appear to function in parallel to coordinatively adapt growth and
      stress responses in plants. Recent evidence also postulates their crucial roles
      in nuclear functions as they interact with the key players of chromatin
      structure, yet other nuclear functions remain largely unknown.
      Phosphatidylinositol monophosphate 5-kinase interacts with and represses a
      cytosolic neutral invertase, a key enzyme of sugar metabolism suggesting a
      crosstalk between lipid and sugar signaling. Besides phosphatidylinositol, myo
      inositol derived galactinol and associated raffinose-family oligosaccharides are
      emerging as antioxidants and putative signaling compounds too. Importantly, myo
      inositol polyphosphate 5-phosphatase (5PTase) acts, depending on sugar status, as
      a positive or negative regulator of a global energy sensor, SnRK1. This implies
      that both myo-inositol- and sugar-derived (e.g. trehalose 6-phosphate) molecules
      form part of a broad regulatory network with SnRK1 as the central regulator.
      Recently, it was shown that the transcription factor bZIP11 also takes part in
      this network. Moreover, a functional coordination between neutral invertase and
      hexokinase is emerging as a sweet network that contributes to oxidative stress
      homeostasis in plants. In this review, we focus on myo-inositol, its direct and
      more downstream derivatives (galactinol, raffinose), and the contribution of
      their associated networks to plant stress tolerance.

PMID- 21889045
TI  - The hunt for plant nitric oxide synthase (NOS): is one really needed?
AB  - Nitric oxide (NO) production is associated with many physiological situations in
      plants, and NO is a key signaling molecule throughout the lifespan of a plant.
      The complexity of the underlying signaling events are just starting to be
      unraveled. The basis for nitric oxide signaling, the production of the signaling
      molecule itself, is far from understood in plants. While in animals, three
      homologous NO synthases (NOS) isoforms have been identified, yet in higher plants
      no corresponding enzymes are known so far. More than half a dozen NO productive
      reactions have been observed in plants but only few of them have been thoroughly
      investigated. It remains to be elucidated how these parts act together to form
      the sophisticated NO signaling network observed in plants.

PMID- 21889046
TI  - Arabidopsis LOS5/ABA3 overexpression in transgenic tobacco (Nicotiana tabacum cv.
      Xanthi-nc) results in enhanced drought tolerance.
AB  - Drought is a major environmental stress factor that affects growth and
      development of plants. Abscisic acid (ABA), osmotically active compounds, and
      synthesis of specific proteins, such as proteins that scavenge oxygen radicals,
      are crucial for plants to adapt to water deficit. LOS5/ABA3 (LOS5) encodes
      molybdenum-cofactor sulfurase, which is a key regulator of ABA biosynthesis. We
      overexpressed LOS5 in tobacco using Agrobacterium-mediated transformation.
      Detached leaves of LOS5-overexpressing seedlings showed lower transpirational
      water loss than that of nontransgenic seedlings in the same period under normal
      conditions. When subjected to water-deficit stress, transgenic plants showed less
      wilting, maintained higher water content and better cellular membrane integrity,
      accumulated higher quantities of ABA and proline, and exhibited higher activities
      of antioxidant enzymes, i.e., superoxide dismutase, catalase, peroxidase and
      ascorbate peroxidase, as compared with control plants. Furthermore, LOS5
      overexpressing plants treated with 30% polyethylene glycol showed similar
      performance in cellular membrane protection, ABA and proline accumulation, and
      activities of catalase and peroxidase to those under drought stress. Thus,
      overexpression of LOS5 in transgenic tobacco can enhance drought tolerance.

PMID- 21889047
TI  - Genetic variation, population structure, and linkage disequilibrium in European
      elite germplasm of perennial ryegrass.
AB  - Perennial ryegrass (Lolium perenne L.) is a highly valued temperate climate grass
      species grown as forage crop and for amenity uses. Due to its outbreeding nature
      and recent domestication, a high degree of genetic diversity is expected among
      cultivars. The aim of this study was to assess the extent of linkage
      disequilibrium (LD) within European elite germplasm and to evaluate the
      appropriate methodology for genetic association mapping in perennial ryegrass. A
      high level of genetic diversity was observed in a set of 380 perennial ryegrass
      elite genotypes when genotyped with 40 SSRs and 2 STS markers. A Bayesian
      structure analysis identified two subpopulations, which were confirmed by
      principal coordinate analysis (PCoA). One subpopulation consisted mainly of
      genotypes originating from the UK, while germplasm mostly from Continental Europe
      was grouped into the second subpopulation. LD (r(2)) decay was rapid and occurred
      within 0.4cM across European varieties, when population structure was taken into
      consideration. However, an extended LD of up to 6.6cM was detected within the
      variety Aberdart. High genetic diversity and rapid LD decay provide means for
      high resolution association mapping in elite materials of perennial ryegrass.
      However, different strategies need to be applied depending on the material used.
      Genome-wide association study (GWAS) with several hundred markers can be applied
      within synthetic varieties to identify large (up to 10cM) genomic regions
      affecting trait variation. A combination of available and novel DNA markers is
      needed to achieve resolution required for GWAS in elite breeding materials. An
      even higher marker density of several million SNPs might be needed for GWAS in
      diverse ecotype collections, potentially resulting in quantitative trait
      polymorphism (QTP) identification.

PMID- 21889048
TI  - Involvement of Arabidopsis NAC transcription factor in the regulation of 20S and
      26S proteasomes.
AB  - We investigated the transcript levels of 13 proteasome subunit genes, the protein
      levels of proteasomes, and the activities of the 26S proteasome in ANAC078
      overexpressing Arabidopsis plants (Ox-ANAC078) and knockout ANAC078 (KO-ANAC078)
      mutants. The transcript levels and the protein levels of proteasomes were
      increased in the Ox-ANAC078 plants compared with the wild-type plants and KO
      ANAC078 mutants under normal conditions and high-light (HL) stress. Although the
      activities of the 26S proteasome were decreased in all the plants under HL
      stress, they were higher in the Ox-ANAC078 plants than wild-type plants and KO
      ANAC078 mutants under normal conditions and HL stress. These findings suggest
      that ANAC078 regulates the levels of proteasomes. To explore the function of the
      increased levels of proteasomes to HL stress, we assessed the tolerance to HL
      stress of the Ox-ANAC078 plants and KO-ANAC078 mutants. The photosystem II
      activities of Ox-ANAC078 remained high compared with those of the wild-type
      plants and KO-ANAC078 mutants under HL stress, suggesting that ANAC078 may play
      an important role in the response and adaptation to HL stress.

PMID- 21889049
TI  - Responses of Gmelina arborea, a tropical deciduous tree species, to elevated
      atmospheric CO2: growth, biomass productivity and carbon sequestration efficacy.
AB  - The photosynthetic response of trees to rising CO(2) concentrations largely
      depends on source-sink relations, in addition to differences in responsiveness by
      species, genotype, and functional group. Previous studies on elevated CO(2)
      responses in trees have either doubled the gas concentration (>700 MUmol mol(-1))
      or used single large addition of CO(2) (500-600 MUmol mol(-1)). In this study,
      Gmelina arborea, a fast growing tropical deciduous tree species, was selected to
      determine the photosynthetic efficiency, growth response and overall source-sink
      relations under near elevated atmospheric CO(2) concentration (460 MUmol mol(
      1)). Net photosynthetic rate of Gmelina was ~30% higher in plants grown in
      elevated CO(2) compared with ambient CO(2)-grown plants. The elevated CO(2)
      concentration also had significant effect on photochemical and biochemical
      capacities evidenced by changes in F(V)/F(M), ABS/CSm, ET(0)/CSm and RuBPcase
      activity. The study also revealed that elevated CO(2) conditions significantly
      increased absolute growth rate, above ground biomass and carbon sequestration
      potential in Gmelina which sequestered ~2100 g tree(-1) carbon after 120 days of
      treatment when compared to ambient CO(2)-grown plants. Our data indicate that
      young Gmelina could accumulate significant biomass and escape acclimatory down
      regulation of photosynthesis due to high source-sink capacity even with an
      increase of 100 MUmo lmol(-1) CO(2).

PMID- 21889050
TI  - CaMF2, an anther-specific lipid transfer protein (LTP) gene, affects pollen
      development in Capsicum annuum L.
AB  - Based on the gene differential expression analysis performed by cDNA-amplified
      fragment length polymorphism (cDNA-AFLP) in the genic male sterile-fertile line
      114AB of Capsicum annuum L., a variety of differentially expressed cDNA fragments
      were detected in fertile or sterile lines. A transcript-derived fragment (TDF)
      specifically accumulated in the flower buds of fertile line was isolated, and the
      corresponding full-length cDNA and DNA were subsequently amplified.
      Bioinformatical analyses of this gene named CaMF2 showed that it encodes a lipid
      transfer protein with 94 amino acids. Spatial and temporal expression patterns
      analysis indicated that CaMF2 was an anther-specific gene and the expression of
      CaMF2 was detected only in flower buds at stage 3-7 of male fertile line with a
      peak expression at stage 4, but not detected in the roots, tender stems, fresh
      leaves, flower buds, open flowers, sepals, petals, anthers or pistils of male
      sterile line. Further, inhibition of the CaMF2 by virus-induced gene silencing
      (VIGS) method resulted in the low pollen germination ability and shriveled pollen
      grains. All these evidence showed that CaMF2 had a vital role in pollen
      development of C. annuum.

PMID- 21889051
TI  - The irradiance dependent transcriptional regulation of AtCLPB3 expression.
AB  - Transcript abundance analysis was applied to determine whether expression of
      genes coding for 50 principal constituents of chloroplast and mitochondria
      proteolytic machinery, i.e. isoforms of proteases and regulatory subunits of Clp
      and FtsH families as well as Deg group of chymotrypsin family are differentially
      expressed in response to acclimation to elevated irradiance. Of 50 genes analysed
      only a single one coding for ClpB3 regulatory subunit was found to be up
      regulated and gene coding for Deg2 to be down-regulated significantly during
      acclimation to excessive irradiance conditions. Hierarchical clustering of
      transcript abundance data revealed that CLPB3 co-expressed tightly with genes
      coding for PAP1, GBF6 and bHLH family member transcription factors during the
      acclimation. It was found that CLPB3 contains cis-regulatory elements able to
      bind all three transcription factors. By performing analyses of publicly
      available transcriptomic data sets from a range of long-term abiotic stresses we
      suggest that PAP1 may mediate condition-dependent transcriptional response of
      CLPB3, induced by a group of long-term abiotic stresses.

PMID- 21889052
TI  - AtNG1 encodes a protein that is required for seed germination.
AB  - The pentatricopeptide repeat (PPR) family of eukaryotic proteins has numerous
      members in plants and is important for plant development. In the present study,
      we cloned a novel PPR gene, designated AtNG1, and characterized the ng1
      Arabidopsis mutant. Morphological and structural observation of an ng1 mutant
      revealed that its sexual reproduction and seed formation processes are
      essentially normal. The mature embryonic root of ng1 is fully developed and has a
      well-differentiated structure; however, ng1 seeds cannot germinate, even when
      supplied with supplemental hormones and nutrition. Further investigation showed
      that embryo expansion and root cell elongation fails to occur after water
      imbibitions. Transient gene expression analysis indicated that AtNG1 localizes in
      mitochondrion. This implies that the deficiency of mitochondrion function might
      be the reason for the failed seed germination. Thus, our finding confirmed that
      AtNG1 plays a critical role in the early process of seed germination.

PMID- 21889053
TI  - Cell wall-associated malate dehydrogenase activity from maize roots.
AB  - Isolated cell walls from maize (Zea mays L.) roots exhibited ionically and
      covalently bound NAD-specific malate dehydrogenase activity. The enzyme catalyses
      a rapid reduction of oxaloacetate and much slower oxidation of malate. The
      kinetic and regulatory properties of the cell wall enzyme solubilized with 1M
      NaCl were different from those published for soluble, mitochondrial or plasma
      membrane malate dehydrogenase with respect to their ATP, Pi, and pH dependence.
      Isoelectric focusing of ionically-bound proteins and specific staining for malate
      dehydrogenase revealed characteristic isoforms present in cell wall isolate,
      different from those present in plasma membranes and crude homogenate. Much
      greater activity of cell wall-associated malate dehydrogenase was detected in the
      intensively growing lateral roots compared to primary root with decreased growth
      rates. Presence of Zn(2+) and Cu(2+) in the assay medium inhibited the activity
      of the wall-associated malate dehydrogenase. Exposure of maize plants to excess
      concentrations of Zn(2+) and Cu(2+) in the hydroponic solution inhibited lateral
      root growth, decreased malate dehydrogenase activity and changed isoform
      profiles. The results presented show that cell wall malate dehydrogenase is truly
      a wall-bound enzyme, and not an artefact of cytoplasmic contamination, involved
      in the developmental processes, and detoxification of heavy metals.

PMID- 21889054
TI  - Analysis of IIId, IIIe and IVa group basic-helix-loop-helix proteins expressed in
      Arabidopsis root epidermis.
AB  - Differentiation of Arabidopsis epidermal cells into root hairs and trichomes is a
      functional model system for understanding plant cell development. Previous
      studies showed that one of the Arabidopsis basic-helix-loop-helix (AtbHLH)
      proteins, GLABRA3 (GL3), is involved in root-hair and trichome differentiation.
      We analyzed 11 additional AtbHLH genes with homology to GL3. Estimation of the
      phylogeny based on amino acid sequences of the bHLH region suggests that 11
      AtbHLH genes used in this study evolved by duplications of a single common GL3
      ancestor. Promoter-GUS analysis showed that AtbHLH006, AtbHLH013, AtbHLH017 and
      AtbHLH020 were expressed in roots. Among them, AtbHLH006 and AtbHLH020 were
      preferentially expressed in root epidermal non-hair cells. Consistent with the
      expression patterns from promoter-GUS analysis, GFP fluorescence was observed in
      the nuclei of root epidermal non-hair cells of AtbHLH006p::AtbHLH006:GFP and
      AtbHLH020p::AtbHLH020:GFP transgenic plants. However, AtbHLH006 and AtbHLH0020
      proteins did not interact with epidermis-specific MYB proteins and TTG1. Taken
      together, AtbHLH006 and AtbHLH020 may function in root epidermal cells, but other
      GL3-like bHLH proteins may have evolved to regulate different processes.

PMID- 21889055
TI  - Positive effects of temperature and growth conditions on enzymatic and
      antioxidant status in lettuce plants.
AB  - The contents of two bioactive compounds (polyphenols and flavonoids) and their
      antioxidant and enzyme activities were determined in the leaves of six lettuce
      (Latuca sativa L.) cultivars subjected to 4 different day/night temperatures for
      6 weeks. The total polyphenol and anthocyanin contents and the corresponding
      antioxidant activities were the highest at 13/10 degrees C and 20/13 degrees C,
      followed by 25/20 degrees C and 30/25 degrees C. The enzymatic activities of
      polyphenol oxidase (PPO) and phenylalanine ammonia-lyase (PAL) were also the
      highest at low day/night temperatures, but the peroxidase (POD) activity was
      decreased at low day/night temperatures and increased at high day/night
      temperatures. The most significant positive correlation existed between
      anthocyanin content and PPO activity, total polyphenols and their antioxidant
      activities. The results showed that at relatively low temperatures, lettuce
      plants have a high antioxidant and enzymatic status. These results provide
      additional information for the lettuce growers.

PMID- 21889056
TI  - Proteomic changes in grape embryogenic callus in response to Agrobacterium
      tumefaciens-mediated transformation.
AB  - Agrobacterium tumefaciens-mediated transformation is highly required for studies
      of grapevine gene function and of huge potential for tailored variety
      improvements. However, grape is recalcitrant to transformation, and the
      underlying mechanism is largely unknown. To better understand the overall
      response of grapevine to A. tumefaciens-mediated transformation, the proteomic
      profile of cv. Prime embryogenic callus (EC) after co-cultivation with A.
      tumefaciens was investigated by two-dimensional electrophoresis and MALDI-TOF-MS
      analysis. Over 1100 protein spots were detected in both inoculated and control
      EC, 69 of which showed significantly differential expression; 38 of these were
      successfully identified. The proteins significantly up-regulated 3 d after
      inoculation were PR10, resistance protein Pto, secretory peroxidase, cinnamoyl
      CoA reductase and different expression regulators; down-regulated proteins were
      ascorbate peroxidase, tocopherol cyclase, Hsp 70 and proteins involved in the
      ubiquitin-associated protein-degradation pathway. A. tumefaciens transformation
      induced oxidative burst and modified protein-degradation pathways were further
      validated with biochemical measurements. Our results reveal that agrobacterial
      transformation markedly inhibits the cellular ROS-removal system, mitochondrial
      energy metabolism and the protein-degradation machinery for misfolded proteins,
      while the apoptosis signaling pathway and hypersensitive response are
      strengthened, which might partially explain the low efficiency and severe EC
      necrosis in grape transformation.

PMID- 21889057
TI  - Inflorescence abnormalities occur with overexpression of Arabidopsis lyrata FT in
      the fwa mutant of Arabidopsis thaliana.
AB  - Arabidopsis thaliana is a quantitative long-day plant with the timing of the
      floral transition being regulated by both endogenous signals and multiple
      environmental factors. fwa is a late-flowering mutant, and this phenotype is due
      to ectopic FWA expression caused by hypomethylation at the FWA locus. The floral
      transition results in the activation of the floral development process, the key
      regulators being the floral meristem identity genes, AP1 (APETALA1) and LFY
      (LEAFY). In this study, we describe inflorescence abnormalities in plants
      overexpressing the Arabidopsis lyrata FT (AlFT) and A. thaliana FWA (AtFWA) genes
      simultaneously. The inflorescence abnormality phenotype was present in only a
      proportion of plants. All plants overexpressing both AlFT and AtFWA flowered
      earlier than fwa, suggesting that the inflorescence abnormality and earlier
      flowering time are caused independently. The inflorescence abnormality phenotype
      was similar to that of the double mutant of ap1 and lfy, and AP1 and LFY genes
      were down-regulated in the abnormal inflorescences. From these results, we
      suggest that not only does ectopic AtFWA expression inhibit AtFT/AlFT function to
      delay flowering but that overexpression of AtFWA and AlFT together inhibits AP1
      and LFY function to produce abnormal inflorescences.

PMID- 21889058
TI  - Reliability and the smallest detectable difference of measurements on 3
      dimensional cone-beam computed tomography images.
AB  - INTRODUCTION: The aim of this study was to determine the reliability and the
      measurement error (by means of the smallest detectable error) of 17 commonly used
      cephalometric measurements made on 3-dimensional (3D) cone-beam computed
      tomography images. METHODS: Twenty-five cone-beam computed tomography scans were
      randomly selected, and 3D images were rendered, segmented, and traced with the
      SimPlant Ortho Pro software (version 2.1, Materialise Dental, Leuven, Belgium).
      This was repeated twice by 2 observers during 2 sessions at least 1 week apart.
      Measurement error was determined by means of the smallest detectable difference.
      Differences were analyzed with Wilcoxon signed rank tests. Intraobserver and
      interobserver reliability values were calculated by means of intraclass
      correlation coefficients (ICC) based on absolute agreement. RESULTS: There were
      great variations of measurement errors between the angular (range, 0.88 degrees 
      6.29 degrees ) and linear (range, 1.33-3.56 mm) variables. The greatest measuring
      error was associated with the dental measurements U1-FHPL, L1-MdPL. and L1-FHPL
      (range, 3.80 degrees -6.29 degrees ). ANB angle was the only variable with a
      measuring error of 1 degrees  or less for both observers. The intraobserver
      agreement of all measurements was very good (ICC, 0.86-0.99). Except for SN-FHPL
      (ICC, 0.76), interobserver agreement was very good (ICC, >0.88). CONCLUSIONS: The
      measurement errors of 3D cephalometric measurements (except for the ANB angle)
      can be considered clinically relevant. This questions the use of linear and
      angular 3D measurements to detect true treatment effects when a high level of
      accuracy is required.

PMID- 21889060
TI  - Photoelastic analysis of forces generated by T-loop springs made with stainless
      steel or titanium-molybdenum alloy.
AB  - INTRODUCTION: The purpose of this study was to use photoelastic analysis to
      compare the system of forces generated by retraction T-loop springs made with
      stainless steel and titanium-molybdenum alloy (TMA) (Ormco, Glendora, Calif) with
      photoelastic analysis. METHODS: Three photoelastic models were used to evaluate
      retraction T-loop springs with the same preactivations in 2 groups. In group 1,
      the loop was constructed with a stainless steel wire, and 2 helicoids were
      incorporated on top of the T-loop; in group 2, it was made with TMA and no
      helicoids. RESULTS: Upon using the qualitative analysis of the fringe order in
      the photoelastic model, it was observed that the magnitude of force generated by
      the springs in group 1 was significantly higher than that in group 2. However,
      both had symmetry for the active and reactive units related to the system of
      force. CONCLUSIONS: Both springs had the same mechanical characteristics. TMA
      springs showed lower force levels.

PMID- 21889059
TI  - Metallic ions released from stainless steel, nickel-free, and titanium
      orthodontic alloys: toxicity and DNA damage.
AB  - INTRODUCTION: The aims of this study were to determine the amounts of metallic
      ions that stainless steel, nickel-free, and titanium alloys release to a culture
      medium, and to evaluate the cellular viability and DNA damage of cultivated human
      fibroblasts with those mediums. METHODS: The metals were extracted from 10
      samples (each consisting of 4 buccal tubes and 20 brackets) of the 3 orthodontic
      alloys that were submerged for 30 days in minimum essential medium. Next, the
      determination of metals was performed by using inductively coupled plasma mass
      spectrometry, cellular viability was assessed by using the tetrazolium reduction
      assay (MTT assay) (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium
      bromide), and DNA damage was determined with the Comet assay. The metals measured
      in all the samples were Ti(47), Cr(52), Mn(55), Co(59), Ni(60), Mo(92), Fe(56),
      Cu(63), Zn(66), As(75), Se(78), Cd(111), and Pb(208). RESULTS: The cellular
      viability of the cultured fibroblasts incubated for 7 days with minimum essential
      medium, with the stainless steel alloy submerged, was close to 0%. Moreover, high
      concentrations of titanium, chromium, manganese, cobalt, nickel, molybdenum,
      iron, copper, and zinc were detected. The nickel-free alloy released lower
      amounts of ions to the medium. The greatest damage in the cellular DNA, measured
      as the olive moment, was also produced by the stainless steel alloy followed by
      the nickel-free alloy. Conversely, the titanium alloy had an increased cellular
      viability and did not damage the cellular DNA, as compared with the control
      values. CONCLUSIONS: The titanium brackets and tubes are the most biocompatible
      of the 3 alloys studied.

PMID- 21889061
TI  - Comparison of 6 cone-beam computed tomography systems for image quality and
      detection of simulated canine impaction-induced external root resorption in
      maxillary lateral incisors.
AB  - INTRODUCTION: The most frequent adverse effect of canine impaction is resorption
      of the adjacent incisors. The subjective image quality and the radiographic
      diagnostic accuracy for detection of simulated canine-induced external root
      resorption lesions in maxillary lateral incisors were compared among 6 cone-beam
      computed tomography (CBCT) systems in vitro. METHODS: A child cadaver skull in
      the early mixed dentition was obtained. This skull had an impacted maxillary left
      canine and allowed a reliable simulation. Simulated root resorption cavities were
      created in 8 extracted maxillary left lateral incisors by the sequential use of
      0.16-mm diameter round burs in the distopalatal root surface. Cavities of varying
      depths were drilled in the middle or apical thirds of each tooth root according
      to 3 setups: slight (0.15, 0.20, and 0.30 mm), moderate (0.60 and 1.00 mm), and
      severe (1.50, 2.00, and 3.00 mm) resorption. The lateral incisors, including 2
      intact teeth, were repositioned individually in the alveolus with approximal
      contacts to the impacted maxillary left canine. Six sets of radiographic images
      were obtained with 3D Accuitomo-XYZ Slice View Tomograph (J. Morita, Kyoto,
      Japan), Scanora 3D CBCT (Soredex, Tuusula, Finland), Galileos 3D Comfort (Sirona
      Dental Systems, Bensheim, Germany), Picasso Trio (E-WOO Technology, Giheung-gu,
      Republic of Korea), ProMax 3D (Planmeca OY, Helsinki, Finland), and Kodak 9000 3D
      (Trophy, Croissy-Beaubourg, France) for each tooth setup. The CBCT images were
      acquired and subsequently analyzed by 12 observers. Linear models for repeated
      measures were used to compare the CBCT systems for the image quality and the
      degree of agreement between the diagnosed severity of root resorption and the
      true severity. RESULTS: The differences in the image quality between CBCT systems
      were statistically significant (P <0.001). The root resorption scores between
      CBCT systems showed a significantly higher score for the ProMax when compared
      with the Galileos and the Kodak. However, the differences in agreement between
      the diagnosed severity of root resorption and the true severity for all
      resorption sizes were not significantly different (P >0.05) among the different
      CBCT systems. CONCLUSIONS: High image quality is important when detecting root
      resorption. The CBCT systems used in this study had high accuracy with no
      significant differences between them in the detection of the severity of root
      resorption.

PMID- 21889062
TI  - Effect of miniscrew placement torque on resistance to miniscrew movement under
      load.
AB  - INTRODUCTION: The primary stability of orthodontic anchorage miniscrews is
      believed to result from mechanical interlock, with success based upon a number of
      variables, including screw diameter, angle of placement, monocortical vs
      bicortical placement, placement through attached or unattached soft tissue,
      presence or absence of a pilot hole, periscrew inflammation, and maximum
      placement torque. The purpose of this ex-vivo study was to further explore the
      relationship between maximum placement torque during miniscrew placement and
      miniscrew resistance to movement under load. METHODS: Ninety-six titanium screws
      were placed into 24 hemi-maxillae and 24 hemi-mandibles from cadavers between the
      first and second premolars by using a digital torque screwdriver. All screws were
      subjected to a force parallel to the occlusal plane, pulling mesially until the
      miniscrews were displaced by 0.6 mm. The Spearman rank correlation test was used
      to evaluate whether there was an increasing or a decreasing relationship between
      maximum placement torque of the screws, miniscrew resistance to movement, and
      bone thickness. A paired-sample t test and the nonparametric Wilcoxon signed rank
      test were used to compare maximum placement torque, bone thickness, and miniscrew
      resistance to movement between coronally positioned and apically positioned
      screws in the maxilla and the mandible, and between screws placed in the maxilla
      vs screws placed in the mandible. Additionally, 1-way analysis of variance
      (ANOVA) with the post-hoc Tukey-Kramer test was used to determine whether there
      was a significant difference in miniscrew resistance to movement for screws
      placed with maximum torque of <5 Ncm, 5 to 10 Ncm, and >10 Ncm. RESULTS: The mean
      difference in miniscrew resistance to movement between maximum placement torque
      groupings, <5 Ncm, 5 to 10 Ncm, and >10 Ncm, increased throughout the deflection
      range of 0.0 to 0.6 mm. As deflection increased to 0.12 to 0.33 mm, the mean
      resistance to movement for miniscrews with maximum placement torque of 5 to 10
      Ncm was statistically greater than for screws with maximum placement torque <5
      Ncm (P <0.05). As deflection increased to 0.34 to 0.60 mm, the mean resistance to
      movement for miniscrews with maximum placement torque of 5 to 10 Ncm and >10 Ncm
      was significantly greater than for screws with maximum placement torque <5 Ncm (P
      <0.05). At no deflection was there a significant difference in resistance to
      movement between the 2 miniscrew groups with higher placement torque values of 5
      to 10 Ncm and >10 Ncm. CONCLUSIONS: Ex vivo, the mean resistance to movement of
      miniscrews with higher maximum placement torque was greater than the resistance
      to movement of those with lower maximum placement torque.

PMID- 21889063
TI  - Comparative assessment of conventional and self-ligating appliances on the effect
      of mandibular intermolar distance in adolescent nonextraction patients: a single
      center randomized controlled trial.
AB  - INTRODUCTION: Our aim in this study was to compare intermolar widths after
      alignment of crowded mandibular dental arches in nonextraction adolescent
      patients between conventional and self-ligating brackets. METHODS: Fifty patients
      were included in this randomized controlled trial according to the following
      inclusion criteria: nonextraction treatment in both arches, eruption of all
      mandibular teeth, no spaces in the mandibular arch, mandibular irregularity index
      from canine to canine greater than 2 mm, and no therapeutic intervention planned
      involving intermaxillary or other intraoral or extraoral appliances including
      elastics before the end of the observation period. The patients were randomized
      into 2 groups: the first received a conventional appliance, and the other a
      passive self-ligating appliance, both with a 0.022-in slot. The amount of
      crowding of the mandibular dentition at baseline was assessed by using the
      irregularity index. Intermolar width was investigated with statistical methods of
      linear regression analysis. On an exploratory basis, the effect of appliance type
      on intercanine width was also assessed. Additionally, the effects of appliance
      type on time to alignment and crowding on time to alignment were assessed by
      using the Cox proportional hazards model. RESULTS: No evidence of difference in
      intermolar width was found between the 2 bracket systems (beta = 0.30; 95% CI, 
      0.3 to 0.9; P = 0.30). No evidence of difference in intercanine width was
      observed between the 2 bracket systems (beta = 0.33; 95% CI, -0.8 to 0.1; P =
      0.15). The time to reach alignment did not differ between appliance systems
      (hazard ratio, 0.68; 95% CI, 0.4 to 1.2; P = 0.21), whereas the amount of
      crowding was a significant predictor of the required time to reach alignment
      (hazard ratio, 0.88; 95% CI, 0.8 to 0.9; P = 0.02). CONCLUSIONS: The use of
      conventional or self-ligating brackets does not seem to be an important predictor
      of mandibular intermolar width in nonextractions patients when the same wire
      sequence is used.

PMID- 21889064
TI  - How do you determine the quality of the evidence?

PMID- 21889066
TI  - What happened to the alveolar bone during retraction?

PMID- 21889067
TI  - A note about sample size.

PMID- 21889069
TI  - Incidence and effects of genetic factors on canine impaction.

PMID- 21889071
TI  - Confidentiality: to honor or to override?

PMID- 21889073
TI  - Effect of fluoridated chewing sticks (Miswaks) on white spot lesions in
      postorthodontic patients.
AB  - INTRODUCTION: This article illustrates a new treatment method and evaluates the
      effect of the frequent use of fluoridated chewing sticks (miswaks) on the
      remineralization of white spot lesions (WSLs) diagnosed at debonding. METHODS:
      Thirty-seven orthodontic patients (mean age, 17.2 years), with a minimum of 4
      WSLs on the buccal surfaces of the maxillary incisors, canines, premolars, and
      first molars after orthodontic therapy, were enrolled in a double-blind,
      randomized, longitudinal trial lasting 6 weeks. The subjects were divided into 2
      groups using fluoridated miswaks impregnated in 0.5% sodium fluoride (test group,
      n = 19) and nonfluoridated miswaks (control group, n = 18). A custom-made mouth
      tray, covering half of the maxillary dentition, was used while brushing with the
      miswaks 5 times per day. The WSLs were scored by using a DIAGNOdent pen (KaVo,
      Biberach, Germany) and with the International Caries Detection and Assessment
      System (ICDAS II) index, at baseline and 2, 4, and 6 weeks after debonding.
      RESULTS: Both the DIAGNOdent readings and the ICDAS II index of the WSLs
      decreased in the test group on the uncovered side of the dentition but not on the
      covered side during the 6-week trial (P <0.0001). There was also a slight
      improvement in the control group (not significant). There was a strong
      correlation between the DIAGNOdent values and the ICDAS II index when all the
      data were pooled (P <0.001). CONCLUSIONS: The frequent use of fluoridated miswaks
      had a remineralizing effect on WSLs. The DIAGNOdent pen might be a useful tool
      for diagnosing and monitoring changes of WSLs over a relatively short period of
      time.

PMID- 21889074
TI  - Cytotoxicity, genotoxicity, and metal release in patients with fixed orthodontic
      appliances: a longitudinal in-vivo study.
AB  - INTRODUCTION: Treatment with fixed orthodontic appliances in the corrosive
      environment of the oral cavity warrants in-vivo investigations of
      biocompatibility. METHODS: Eighteen control and 28 treated subjects were
      evaluated longitudinally. Four combinations of brackets and archwires were
      tested. Buccal mucosa cell samples were collected before treatment, and 3 and 6
      months after appliance placement. The cells were processed for cytotoxicity,
      genotoxicity, and nickel and chromium contents. RESULTS: In the treatment group,
      buccal mucosa cell viability values were 8.1% at pretreatment, and 6.4% and 4.5%
      at 3 and 6 months, respectively. The composite score, a calculated DNA damage
      value, decreased from 125.6 to 98.8 at 6 months. Nickel cellular content
      increased from 0.52 to 0.68 and 0.78 ng per milliliter, and chromium increased
      from 0.31 to 0.41 and 0.78 ng per milliliter at 3 and 6 months, respectively.
      Compared with the control group, the treated subjects showed significant
      differences for DNA damage and chromium content at 3 months only. CONCLUSIONS:
      Fixed orthodontic appliances decreased cellular viability, induced DNA damage,
      and increased the nickel and chromium contents of the buccal mucosa cells.
      Compared to the control group, these changes were not evident at 6 months,
      possibly indicating tolerance for or repair of the cells and the DNA.

PMID- 21889075
TI  - Attitudes, awareness, and barriers toward evidence-based practice in
      orthodontics.
AB  - INTRODUCTION: The purpose of this study was to evaluate the attitudes, awareness,
      and barriers toward evidence-based practice. METHODS: A survey consisting of 35
      questions pertaining to the use of scientific evidence in orthodontics was sent
      to 4771 members of the American Association of Orthodontists in the United
      States. Each respondent's age, attainment of a master's degree, and whether he or
      she was currently involved with teaching were ascertained. To minimize bias, the
      survey questions were phrased as an examination of the use of scientific
      literature in orthodontics. RESULTS: A total of 1517 surveys were received
      (response rate, 32%). Most respondents had positive attitudes toward, but a poor
      understanding of, evidence-based practice. The major barrier identified was
      ambiguous and conflicting research. Younger orthodontists were more aware, had a
      greater understanding, and perceived more barriers than did older orthodontists.
      Orthodontists involved in teaching were more aware, had a greater understanding,
      and reported fewer barriers than those not involved with teaching. Those with
      master's degrees had a greater understanding of evidence-based practice than
      those without degrees. CONCLUSIONS: Educational initiatives are needed to
      increase the understanding and use of evidence-based practice in orthodontics.

PMID- 21889076
TI  - Transverse dentoalveolar changes after slow maxillary expansion.
AB  - INTRODUCTION: In this study, we evaluated the transverse dentoalveolar changes in
      the maxillary first molar region after early treatment with the quad-helix
      appliance. METHODS: Seventy-three consecutive patients (39 boys, 34 girls) who
      had phase 1 quad-helix treatment were evaluated with cone-beam computed
      tomography scans taken before phase 1 (mean age, 9.2 years) and phase 2 (mean
      age, 11.9 years) treatments. Buccal bone thickness, buccal cortical plate
      thickness, lingual bone thickness, alveolar width, palatal width, and intermolar
      width were measured by using standardized orientations. RESULTS: Slow palatal
      expansion with the quad-helix decreased buccal bone thickness (1.6 mm +/- 0.8),
      and increased lingual bone thickness (1.6 mm +/- 1.3) and alveolar width (0.5 mm
      +/- 1.0). Intermolar widths and palatal widths increased 6.5 mm +/- 2.9 and 3.9
      mm +/- 1.8, respectively. At the beginning of phase 2, approximately one third of
      the patients showed little or no buccal cortical plate on at least 1 side.
      Patients retained with the Hawley demonstrated some relapse tendencies; patients
      without retention had the greatest relapse tendencies. CONCLUSIONS: Early
      treatment with the quad-helix appliance proved to be highly effective in
      increasing intermolar, palatal, and alveolar widths. The teeth moved through the
      alveolus, leading to substantial decreases in buccal bone thickness and increases
      in lingual bone thickness.

PMID- 21889077
TI  - Measurement of plastic and elastic deformation due to third-order torque in self
      ligated orthodontic brackets.
AB  - INTRODUCTION: Control of root torque is often achieved by introducing a twist in
      a rectangular archwire. The purpose of this study was to investigate third-order
      torque on different types of self-ligated brackets by analyzing the bracket's
      elastic and plastic deformations in conjunction with the expressed torque at
      varying angles of twist. METHODS: An orthodontic bracket was mounted to a load
      cell that measured forces and moments in all directions. The wire was twisted in
      the bracket via a stepper motor, controlled by custom software. Overhead images
      were taken by a camera through a microscope and processed by using optical
      correlation to measure deformation. RESULTS: At the maximum torquing angle of 63
      degrees  with 0.019 * 0.025-in stainless steel wire, the total elastic and
      plastic deformation values were 0.063, 0.033, and 0.137 mm for Damon Q (Ormco,
      Orange, Calif), In-Ovation R (GAC, Bohemia, NY), and Speed (Strite Industries,
      Cambridge, Ontario, Canada), respectively. The total plastic deformation values
      were 0.015, 0.006, and 0.086 mm, respectively, measured at 0 degrees  of
      unloading. CONCLUSIONS: In-Ovation R had the least deformation due to torquing of
      the 3 investigated bracket types. Damon Q and Speed on average had approximately
      2.5 and 14 times greater maximum plastic deformation, respectively, than did In
      Ovation R.

PMID- 21889078
TI  - In-vivo evaluation of salivary nickel and chromium levels in conventional and
      self-ligating brackets.
AB  - INTRODUCTION: Our objective was to evaluate and compare the salivary levels of
      nickel and chromium before and 1, 7, and 30 days after placement of conventional
      and self-ligating appliance systems. METHODS: Twenty women were randomly divided
      into 2 groups. Patients in group 1 had conventional brackets bonded to their
      teeth; in group 2, self-ligating brackets were bonded. Four samples of
      unstimulated saliva were collected from each patient 1 hour before placement of
      the fixed appliance, and 1, 7, and 30 days after placement of the appliance. The
      chemical analyses for nickel and chromium levels were performed with an atomic
      absorption spectrometer (PerkinElmer, Shelton, Conn). Two-way repeated measures
      analysis of variance by ranks (Friedman test) were used to test the statistical
      significance of differences in the concentrations of nickel and chromium before
      and after placement of the appliances. Post-hoc pair-wise comparisons among
      groups of the same element were calculated by using the Wilcoxon signed rank
      test. A value of P <=0.05 was considered significant. RESULTS: Nickel and
      chromium released into saliva from conventional and self-ligating brackets
      progressively increased from days 1 to 7 and then decreased at day 30. Nickel
      release was less, and chromium release was greater in the conventional bracket
      group. CONCLUSIONS: Both the conventional and the self-ligating brackets did not
      seem to affect significantly the nickel and chromium concentrations in saliva
      during the first month of treatment.

PMID- 21889079
TI  - Treatment strategies for patients with hyperdivergent Class II Division 1
      malocclusion: is vertical dimension affected?
AB  - INTRODUCTION: The dilemma of extraction vs nonextraction treatment, along with
      the uncertain potential of orthodontic treatment to control vertical dimensions,
      still remains among the most controversial issues in orthodontics. The aim of
      this study was to evaluate 2 contradictory treatment protocols for hyperdivergent
      Class II Division 1 malocclusion regarding their effectiveness in controlling
      vertical dimensions. METHODS: The subjects were retrospectively selected from 2
      orthodontic offices that used contrasting treatment protocols. The patients had
      similar hyperdivergent skeletal patterns, malocclusion patterns, skeletal ages,
      and sexes. Group A (29 patients) was treated with 4 first premolar extractions
      and "intrusive" mechanics (eg, high-pull headgear), whereas group B (28 patients)
      was treated nonextraction with no regard to vertical control (eg, cervical
      headgear, Class II elastics). Twenty-seven landmarks were digitized on lateral
      cephalometric radiographs before and after treatment, and 14 measurements were
      assessed. Geometric morphometric methods were also implemented to evaluate size
      and shape differences. RESULTS: As expected, the maxillary and mandibular molars
      translated mesially and the mandibular incisors uprighted in group A but remained
      approximately unchanged in group B. The vertical positions of the molars and the
      incisors were similar between groups before and after treatment, although they
      were altered by treatment or growth. No significant differences were observed in
      the posttreatment skeletal measurements between the 2 groups, including vertical
      variables, which remained unaltered. Permutation tests on Procrustes distances
      between skeletal shapes confirmed these results. CONCLUSIONS: This study
      demonstrated the limitations of conventional orthodontics to significantly alter
      skeletal vertical dimensions. More important factors are probably responsible for
      the development and establishment of the vertical skeletal pattern, such as
      neuromuscular balance and function.

PMID- 21889080
TI  - Computed tomographic characterization of mini-implant placement pattern and
      maximum anchorage force in human cadavers.
AB  - INTRODUCTION: The purpose of this investigation was to characterize the placement
      pattern and factors influencing the primary stability of mini-implants in human
      cadavers. The factors studied were mini-implant length, placement depth, bone
      density, and bone type. METHODS: Sixty standard mini-implants (6, 8, and 10 mm;
      20 of each size) were placed into the maxillas and mandibles of 5 fresh human
      cadavers. Computed tomography imaging was used to measure the placement pattern,
      bone density, and thickness surrounding each device. The mini-implants were
      subsequently subjected to increasing tensile forces (pull-out force) until
      failure, and the maximum mechanical anchorage force of each was recorded with a
      dynamometer. A statistical model was realized by using MATLAB version 7.5.0 with
      Statistics Toolbox 7 (MathWorks, Natick, Mass) including the maximum anchorage
      force, mini-implant length, bone type, placement depth, and density surrounding
      each section of the mini-implant. RESULTS: Placement depth was strongly dependent
      on mini-implant length: 15% of the 6-mm implants failed to anchor their parallel
      sections into cortical bone, but 95% of the 10-mm mini-implant parallel sections
      penetrated beyond the buccal cortical bone; all 20 tips of the 6-mm mini-implants
      (100%) reached cancellous bone, whereas 75% of the 10-mm implants penetrated both
      cortical plates, reaching the lingual cortical bone. Longer mini-implants were
      associated with greater incidences of sinus and bicortical perforations. The
      correlation coefficients between the initial maximum mechanical anchorage force
      and the studied factors were as follows: bone density and placement depth
      combined (r = 0.65, P <0.001), mini-implant length (r = 0.45, P = 0.004), bone
      density (r = 0.42, P = 0.007), and placement depth (r = 0.29, P = 0.06).
      CONCLUSIONS: During mini-implant length selection, the clinician should consider
      the important trade-off between anchorage and risk of placement complications or
      damage to the tissues. Longer mini-implants enable more anchorage; however, they
      are associated with a higher risk of damage to neighboring structures. Placement
      depth and bone density at the site of mini-implant placement are the best
      predictors of primary stability.

PMID- 21889081
TI  - Immediate effects of rapid maxillary expansion with Haas-type and hyrax-type
      expanders: a randomized clinical trial.
AB  - INTRODUCTION: The purposes of this study were to evaluate and compare the
      immediate effects of rapid maxillary expansion (RME) in the transverse plane with
      Haas-type and hyrax-type expanders by using cone-beam computed tomography.
      METHODS: A sample of 33 subjects (mean age, 10.7 years; range, 7.2-14.5 years)
      with transverse maxillary deficiency were randomly divided into 2 groups: Haas (n
      = 18) and hyrax (n = 15). All patients had RME with an initial activation of 4
      quarter turns followed by 2 quarter turns per day until the expansion reached 8
      mm. Cone-beam computed tomography scans were taken before expansion and at the
      end of the RME phase. Maxillary transversal measurements were compared by using
      the mixed analysis of variance (ANOVA) model and the Tukey-Kramer method.
      RESULTS: RME increased all maxillary transverse dimensions (P <0.0001). There was
      less expansion at skeletal than dental levels. The hyrax group had greater
      statistically significant orthopedic effects and less tipping tendency of the
      maxillary first molars compared with the Haas group. CONCLUSIONS: Both appliances
      were efficient in correcting a transverse maxillary deficiency. The pure skeletal
      expansion was greater than actual dental expansion. The hyrax-type expander
      produced greater orthopedic effects than did the Haas-type expander, but this
      effect was less than 0.5 mm per side and might not be clinically significant.

PMID- 21889082
TI  - Extraction of maxillary first molars improves second and third molar inclinations
      in Class II Division 1 malocclusion.
AB  - INTRODUCTION: The aim of this study was to assess the changes in inclination of
      the maxillary second (M2) and third (M3) molars after orthodontic treatment of
      Class II Division 1 malocclusion with extraction of maxillary first molars.
      METHODS: Two groups of subjects were studied. The experimental group consisted of
      37 subjects, 18 boys and 19 girls (mean age, 13.2 +/- 1.62 years). The inclusion
      criteria were white origin, Class II Division 1 malocclusion, overjet >=4 mm, no
      missing teeth or agenesis, and maxillary M3 present. All patients were treated
      with extraction of the maxillary first molars and the Begg technique.
      Standardized lateral cephalometric radiographs were taken at the start of active
      treatment (T1) and at least 3.7 years posttreatment (T2). The control group was
      drawn from the archives of the Nittedal Growth Material (Oslo University, Oslo,
      Norway) and included 54 untreated Class I and Class II subjects,18 boys and 36
      girls (mean age, 13.4 +/- 1.99 years) followed up for a minimum of 3.6 years. M2
      and M3 inclinations relative to the palatal plane (PP) and functional occlusal
      plane (FOP) were measured and compared between groups and time periods. RESULTS:
      M2 to PP inclination improved significantly in both the control group (M2-PP at
      T1, 17.7 degrees  +/- 5.81 degrees , and at T2, 11.9 degrees  +/- 4.61 degrees )
      and the experimental group (M2-PP at T1, 26.7 degrees  +/- 5.75 degrees , and at
      T2, 6.9 degrees  +/- 6.76 degrees ). There were also significant increases of the
      mesial inclination of M3 in the control group (M3-PP at T1, 30.1 degrees  +/-
      8.54 degrees , and at T2, 19.6 degrees  +/- 9.01 degrees ) and extraction group
      (M3-PP at T1, 32.2 degrees  +/- 7.90 degrees , and at T2, 12.8 degrees  +/- 7.36
      degrees ). By using the FOP as the reference system, no significant change in the
      inclination of M2 was observed in the control group, whereas, in the extraction
      group, although more distally inclined at T1, M2 ended up mesially inclined at T2
      (M2-FOP at T1, 14.2 degrees  +/- 4.62 degrees , and at T2, -6.2 degrees  +/- 6.10
      degrees ; P <0.0001). M3 inclinations were similar between the groups at T1 (M3
      FOP control, 17.3 degrees  +/- 9.35 degrees ; M3-FOP experimental, 19.6 degrees 
      +/- 7.37 degrees ), and these improved significantly in both groups. However, M3
      uprighting was almost 4 times greater in the extraction group (M3-FOP from T2-T1,
      5.6 degrees  vs 19.9 degrees ). The greatest distal inclination of M3 at T2 in
      the extraction group was 9.4 degrees , a value attained by only 43% of the
      control group. CONCLUSIONS: Extraction of the maxillary first molars in Class II
      Division 1 patients results in significant uprighting of M2 and M3 and
      facilitates the normal eruption of M3.

PMID- 21889083
TI  - Evaluation of the genotoxic effects of fixed appliances on oral mucosal cells and
      the relationship to nickel and chromium concentrations: an in-vivo study.
AB  - INTRODUCTION: The release of metal ions from fixed orthodontic appliances is a
      source of concern. The aim of this study was to evaluate genotoxic damage in the
      oral mucosal cells of patients wearing fixed appliance, and the nickel and
      chromium ion contents in these cells. METHODS: Twenty patients undergoing
      orthodontic treatment formed the experimental group, and 20 untreated subjects
      comprised the control group. Oral mucosal smears were collected at 2 times: at
      debonding and 30 days after debonding. The smears were stained with Papanicolaou
      stain and studied under a light microscope to evaluate the presence of
      micronuclei. Inductively coupled plasma-mass spectrometry was used to quantify
      the presence of metal ions. The data were subjected to the Mann-Whitney U test
      and the Spearman rank correlation test. RESULTS: The mean micronuclei frequency
      was significantly higher in the treated group than in the control group at
      debonding; the difference was smaller and not statistically significant 30 days
      after debonding. The nickel and chromium ion contents in the experimental group
      were not significantly higher than in the control group. No correlation could be
      established between micronuclei frequency and metal ion content. CONCLUSIONS:
      Nickel and chromium alloys of orthodontic appliances emit metal ions in
      sufficient quantities to induce localized genotoxic effects, but these changes
      revert on removal of the appliances.

PMID- 21889084
TI  - Influence of dental esthetics on social perceptions of adolescents judged by
      peers.
AB  - INTRODUCTION: The relationship between physical appearance and social
      attractiveness is well established in the literature. The purpose of this study
      was to determine whether dental esthetics influenced the perceptions of teens
      when judging a peer's athletic, social, leadership, and academic abilities.
      METHODS: The frontal-face smiling photographs of 10 teenage volunteers were each
      altered to create 1 image with an ideal arrangement of teeth and 1 with a
      nonideal arrangement. Two parallel surveys were constructed with 1 photo
      displaying either an ideal or a nonideal smile image of each subject. If the
      ideal smile image appeared in 1 survey, then the nonideal smile appeared in the
      other. Two hundred twenty-one peer evaluators successfully rated the pictures in
      1 of the surveys by indicating their perception of each subject's athletic,
      social, leadership, and academic abilities. RESULTS: The subjects' photographs
      with ideal smile esthetics were consistently rated higher on average than the
      same subjects' images with nonideal smile esthetics. The differences in ratings
      between ideal and nonideal smiles were significant for perceptions of athletic
      performance (P = 0.0141), popularity (P <0.0001), and leadership ability (P
      <0.0001), but not for academic performance (P = 0.0548). CONCLUSIONS: On average,
      ratings for the ideal smiles in perceived athletic, social, and leadership skills
      were about 10% higher than those given for images with nonideal smiles. Based on
      these findings, it would be expected that orthodontic treatment resulting in
      improved smile esthetics can provide modest social benefits for adolescent
      patients.

PMID- 21889085
TI  - Treatment of ankylosis of the mandibular first molar with orthodontic traction
      immediately after surgical luxation.
AB  - The aim of this article was to report a clinical case of orthodontic treatment in
      a patient with Class II malocclusion and ankylosis of a maxillary first molar.
      Surgical luxation was performed, followed immediately by traction with an
      orthodontic arch with straps. The results obtained were satisfactory, and
      occlusal equilibrium was improved.

PMID- 21889086
TI  - Total alloplastic temporomandibular joint reconstruction combined with
      orthodontic treatment in a patient with idiopathic condylar resorption.
AB  - This case report describes the successful treatment of an adult patient with
      skeletal Class II open-bite malocclusion secondary to idiopathic condylar
      resorption. Total alloplastic joint reconstruction and counterclockwise rotation
      of the maxillomandibular complex combined with orthodontic treatment provided a
      satisfying outcome with maximum functional and esthetic improvement.

PMID- 21889087
TI  - Sturge-Weber syndrome in an orthodontic patient.
AB  - The aim of this article was to describe the Sturge-Weber syndrome in a patient
      with orthodontic requirements. Pathologies involved in this syndrome affect
      facial cranial growth.

PMID- 21889088
TI  - Atypical orthodontic extraction pattern managed by differential en-masse
      retraction against a temporary skeletal anchorage device in the treatment of
      bimaxillary protrusion.
AB  - This report introduces an innovative treatment approach of selecting atypical and
      unconventional teeth for orthodontic extraction without compromising the quality
      of treatment outcomes by using temporary skeletal anchorage devices in patients
      with bimaxillary protrusion. Both patients introduced in this report had solid
      Class I molar relationships with bimaxillary anterior protrusion without facial
      or dental midline asymmetry. Their chief concerns were significant facial
      convexity, which conventionally requires the extraction of all 4 first premolars.
      However, 3 second premolars and 1 first premolar were removed in the first
      patient, and 2 second premolars and 2 first premolars were removed in the second
      patient. All second premolars extracted had previously had root canal treatment
      and large prosthodontic restorations, which resulted in a compromised short
      lifespan of the teeth relative to the natural dentition. To manage these cases of
      asymmetric extraction space in a symmetric dental and skeletal environment, 2
      mini-implants were placed in the posterior maxillary interradicular spaces, 1 on
      each side. Despite the unusual asymmetric extraction of teeth, superimposition of
      the pretreatment and posttreatment cephalometric tracings shows excellent
      treatment outcomes of facial convexity reduction by asymetric maximum retraction
      of the anterior teeth with no change in the molar relationships.

PMID- 21889089
TI  - Accuracy in tooth positioning with a fully customized lingual orthodontic
      appliance.
AB  - INTRODUCTION: To understand orthodontic tooth movement, a method of
      quantification of tooth position discrepancies in 3 dimensions is needed.
      Brackets and wires now can be fabricated by CAD/CAM technology on a setup made at
      the beginning of treatment, so that treatment should produce a reasonably precise
      duplicate of the setup. The extent of discrepancies between the planned and
      actual tooth movements can be quantified by registration of the setup and final
      models. The goal of this study was to evaluate the accuracy of a CAD/CAM lingual
      orthodontic technique. METHODS: Dental casts of 94 consecutive patients from 1
      practice, representing a broad range of orthodontic problems, were scanned to
      create digital models, and then the setup and final models for each patient were
      registered individually for the maxillary and mandibular dental arches.
      Individual tooth discrepancies between the setup and actual outcome were computed
      and expressed in terms of a six-degrees-of-freedom rectangular coordinate system.
      RESULTS: Discrepancies in position and rotation between the setup and outcome
      were small for all teeth (generally less than 1 mm and 4 degrees ) except for the
      second molars, where some larger discrepancies were observed. Faciolingual
      expansion in the posterior teeth was greater in the setup than in the final
      models, especially at the second molars. Linear mixed models showed that age,
      type of tooth, jaw, initial crowding, time in slot-filling wire, use of elastics,
      days in treatment, interproximal reduction, and rebonding, were all influences on
      the final differences, but, for most of these factors, the influence was small,
      explaining only a small amount of the discrepancy between the planned and the
      actual outcomes. CONCLUSION: These fully customized lingual orthodontic
      appliances were accurate in achieving the goals planned at the initial setup,
      except for the full amount of planned expansion and the inclination at the second
      molars. This methodology is the first step toward understanding and measuring
      tooth movement in 3 dimensions.

PMID- 21889090
TI  - Litigation and legislation. Talking trash.

PMID- 21889091
TI  - The evidence pyramid and introduction to randomized controlled trials.

PMID- 21889092
TI  - Seminars in Vascular Surgery. Contemporary issues in hemodialysis access.
      Introduction.

PMID- 21889093
TI  - Brachial-basilic autogenous access.
AB  - The emphasis on autogenous arteriovenous hemodialysis access has increased the
      focus on the brachial-basilic autogenous configuration currently recommended by
      the national guidelines when the cephalic vein is not suitable. The brachial
      basilic autogenous access has been extensively studied and compared with both
      prosthetic (arteriovenous graft [AVG]) and other autogenous accesses. The
      literature suggests that the brachial-basilic autogenous access is superior to
      AVGs in terms of patency, reintervention rates, and infectious complications.
      However, controversy still remains with respect to its role in the treatment
      algorithm and the technical conduct of the operation. This review will address
      the ongoing issues and controversies surrounding the brachial-basilic autogenous
      access and define its role for the hemodialysis access surgeon.

PMID- 21889094
TI  - Alternative autogenous arteriovenous hemodialysis access options.
AB  - An autogenous arteriovenous hemodialysis access (AVF) remains the consensus
      recommended vascular access for individuals requiring hemodialysis. Surgical
      options, strategies, and guidelines have been established by several
      organizations, including the National Kidney Foundation, the Fistula First
      Breakthrough Initiative, and the Society for Vascular Surgery. Establishing a
      successful AVF in a high percentage of patients requires a thorough knowledge of
      the many access options and clinical practice recommendations, in addition to a
      careful clinical history/physical examination, pre- and postoperative ultrasound,
      and further vascular imaging in select patients. The more common AVF
      configurations may not be possible in complex patients because of limited venous
      outflow, arterial insufficiency, or both. However, the vascular access surgeon
      may still be able to construct a successful AVF in these challenging patients by
      utilizing one of several alternative procedures. Avoiding prosthetic
      arteriovenous accesses and central venous catheter-based dialysis is feasible in
      most patients. This article reviews some of the alternative options for
      establishing successful AVFs.

PMID- 21889095
TI  - Balloon angioplasty to facilitate autogenous arteriovenous access maturation: a
      new paradigm for upgrading small-caliber veins, improved function, and
      surveillance.
AB  - Balloon angioplasty maturation is emerging as an important method to increase
      utilization and improve function of autogenous arteriovenous hemodialysis
      accesses (AVFs). Through the sequential dilation of small veins, large-diameter
      AVFs can be created with the inherent benefits of easier cannulation, greater
      overall surface area, improved patency, and fewer complications. A usable AVF can
      be created in a shorter amount of time, decreasing the need for dialysis
      catheters. In addition, selective angioplasty of the AVF inflow and outflow can
      facilitate improved flow rates and increase access longevity. Our approach,
      including primary balloon angioplasty during AVF creation, sequential balloon
      angioplasty maturation, and surveillance fistulagrams will be presented.

PMID- 21889096
TI  - Role of prosthetic hemodialysis access following introduction of the dialysis
      outcome quality and Fistula First Breakthrough Initiatives.
AB  - The emphasis on increasing the use of autogenous hemodialysis access in the
      United States has clearly changed the practice pattern of vascular surgeons
      during the past decade. However, this change has also been associated with an
      increased use of cuffed dialysis catheter and a decrease in the autogenous access
      maturation rate. Future efforts to increase autogenous access use will be
      hampered, in part, by the characteristics and comorbidities of the aging
      hemodialysis population and system-wide health care delivery issues, such as late
      referral for vascular access. As a result, prosthetic access will continue to
      play an important role in providing vascular access for the US hemodialysis
      population. This article reviews contemporary trends and evidence-based
      literature related to autogenous and prosthetic access procedures, as well as
      factors that influence access choice.

PMID- 21889097
TI  - Approach to permanent hemodialysis access in obese patients.
AB  - Obesity has reached an epidemic in the United States and, not surprisingly, there
      has been a dramatic increase in obesity-associated comorbidities, complete with a
      host of new, related surgical challenges. The creation and maintenance of
      permanent hemodialysis access, particularly autogenous access, is generally
      considered more difficult in the obese patient because of the increased risk of
      perioperative complications, as well as a decreased maturation rate. Most of the
      data documenting these adverse outcomes come from retrospective studies and,
      therefore, the reliability of the data is somewhat limited, given the inherent
      selection bias. In the United States, most obese patients dialyze through
      prosthetic access, despite the national initiatives targeted at maximizing
      autogenous access. However, it is possible to construct an autogenous access in
      most patients, including obese patients, presenting for permanent access using
      proper, diligent preoperative imaging and an aggressive postoperative
      surveillance protocol until access maturation. This is facilitated by careful
      preoperative planning and liberal use of multiple diagnostic and therapeutic
      maneuvers to improve overall access function. In this review, the outcomes
      associated with permanent hemodialysis access in the obese are discussed and
      helpful suggestions to facilitate a functional access provided.

PMID- 21889098
TI  - Lower extremity arteriovenous hemodialysis access: an important adjunct in select
      patients.
AB  - Given the current survival rates of patients receiving hemodialysis, it has
      become increasingly common for patients to exhaust their upper extremity access
      options. Likewise, overzealous catheter use can lead to central venous occlusion
      or stenosis, further limiting the upper extremity access options. In these
      patients, use of the lower extremities for access is often required. Fortunately,
      there are a number of options available that have acceptable durability and
      utility. The purpose of this article is to review the various techniques
      available for placement of hemodialysis access in the lower extremity and discuss
      their results.

PMID- 21889099
TI  - HeRO Vascular Access Device.
AB  - Chronic hemodialysis via a tunneled dialysis catheter (TDC) is associated with a
      high incidence of infectious complications and increased mortality and,
      therefore, should only be considered when all other options for vascular access
      are exhausted. The Hemoaccess Reliable Outflow (HeRO) Vascular Access Device
      (Hemosphere, Inc., Minneapolis, MN) is an alternative to the TDC. Early results
      suggests that the infectious complications are significantly less for the HeRO
      device when compared to the TDC, and the secondary patency for the device
      approximates that for prosthetic accesses. The device can be successfully placed
      in >90% of catheter-dependent patients. Chronic hemodialysis via the HeRO Device
      is preferable to TDC use.

PMID- 21889100
TI  - Management of central vein stenoses and occlusions: the critical importance of
      the costoclavicular junction.
AB  - The failure of an autogenous or prosthetic arteriovenous hemodialysis access is
      usually related to the failure of the venous outflow resulting from a stenosis
      somewhere in the venous system, commonly at the venous anastomosis for a
      prosthetic access or within the central veins. The National Kidney Foundation's
      Kidney Disease Outcomes Quality Initiative guidelines state that percutaneous
      transluminal venoplasty with or without stenting is the preferred initial
      treatment for a central venous stenosis, but the results of these therapies have
      been have relatively disappointing when analyzed as a whole. Although endoluminal
      intervention works well (and is, indeed, the primary option) for treating areas
      of stenosis surrounded by soft tissue, we believe stenoses occurring at the
      costoclavicular junction are caused by extrinsic bony compression and, therefore,
      should be considered dialysis-associated venous thoracic outlet syndrome. The
      treatment of venous thoracic outlet syndrome, based on decades of experience,
      generally requires bony decompression for long-term patency. In the last 2 years,
      we have treated 12 patients with dialysis-associated venous thoracic outlet
      syndrome with surgical decompression of the thoracic outlet. Functional patency
      was achieved in 75% of patients at a mean follow-up of 8 months. We would contend
      that not all central vein stenoses are equivalent and that an individualized
      approach is most appropriate based on the extent and anatomic location of the
      lesion.

PMID- 21889101
TI  - Role of stent grafts for the treatment of failing hemodialysis accesses.
AB  - Covered stents or stent grafts are exciting new products with multiple
      applications for patients with vascular disease, including hemodialysis access
      related complications. Although most of the current uses of stent grafts in these
      settings are "off-label" (ie, not approved by the US Food and Drug
      Administration) several studies are currently underway to provide the necessary
      data to support their application. It is clear that stent grafts provide a rapid,
      effective means for endovascular repair of ruptured access vessels. The
      commercially available devices and their current applications for treating access
      related complications, including aneurysms/pseudoaneurysms, venous outflow
      stenoses, cephalic arch lesions, ruptures, and diffuse access stenoses, will be
      reviewed in this article. Available data are reported along with our current
      clinical practice and algorithms.

PMID- 21889102
TI  - Treatment strategies for access-related hand ischemia.
AB  - Access-related hand ischemia, commonly known as "steal syndrome," is one of the
      most challenging and worrisome complications for the access surgeon. The
      construction of an arteriovenous access results in a predictable decrease in the
      perfusion pressure distal to the anastomosis, which can result in ischemia if the
      compensatory mechanisms are inadequate. Several preoperative clinical features
      have been shown to identify patients at risk. The diagnosis of access-related
      hand ischemia is largely a clinical one that can be aided in equivocal cases with
      noninvasive vascular laboratory studies. The treatment goals are to reverse the
      hand ischemia and to preserve the access. There are a variety of different
      remedial treatments, including access ligation, correction of the inflow lesion,
      limiting the flow through the access, proximalization of arterial inflow,
      revision using distal inflow, and distal revascularization with interval
      ligation. The optimal choice is predicated on the timing and severity of symptoms
      in conjunction with the access type, its anticipated durability, patient
      comorbidities, distribution of occlusive disease, and availability of venous
      conduit. The distal revascularization with interval ligation procedure has
      emerged as our optimal treatment and reverses the ischemic symptoms and salvages
      the access in approximately 90% of the cases. It is incumbent on all access
      surgeons to be familiar with the management of access-related hand ischemia. A
      review of the underlying pathophysiology and treatment options will be provided
      along with our current treatment algorithm.

PMID- 21889103
TI  - Role of access surveillance and preemptive intervention.
AB  - Vascular access dysfunction continues to be a major cause of morbidity and
      mortality in the end-stage renal patient. Thrombosis is the primary cause of
      prosthetic arteriovenous access (ie, graft) failure caused by the progressive
      development of neointimal hyperplasia, which eventually leads to a stenosis,
      usually at the venous anastomosis. More than 20 years ago, observational studies
      using a variety of surveillance techniques, coupled with preemptive angioplasty,
      convincingly demonstrated the ability to detect venous stenosis, and elective
      treatment of stenoses significantly decreased both thrombosis and access loss.
      Although multiple observational studies have shown a benefit from surveillance,
      these studies generally had no control population, used historical controls, or
      used incorrect statistical analysis. However, five randomized controlled trials
      that evaluated the effect of graft surveillance coupled with preemptive
      angioplasty have failed to demonstrate a benefit on graft outcomes, including
      prolongation of graft survival. This review will examine the role of access
      surveillance and preemptive angioplasty in achieving the goal of reducing
      vascular access thrombosis and prolonging access survival.

PMID- 21889104
TI  - Is there a way forward for forensic science research in the UK?

PMID- 21889105
TI  - Measuring the validity and reliability of forensic likelihood-ratio systems.
AB  - There has been a great deal of concern recently about validity and reliability in
      forensic science. This paper reviews for a broad target audience metrics of
      validity and reliability (accuracy and precision) which have been applied in
      forensic voice comparison and which are potentially applicable in other branches
      of forensic science. The metric of validity is the log likelihood-ratio cost
      (C(llr)), and the metric of reliability is an empirical estimate of credible
      intervals. A revised procedure for the calculation of credible intervals is
      introduced.

PMID- 21889106
TI  - Chemical enhancement of footwear impressions in blood on fabric - part 1: protein
      stains.
AB  - A range of protein stains were utilised for the enhancement of footwear
      impressions on a variety of fabric types of different colours with blood as a
      contaminant. A semi-automated stamping device was used to deliver test
      impressions at a set force to minimise the variability between impressions;
      multiple impressions were produced and enhanced by each reagent to determine the
      repeatability of the enhancement. Results indicated that while most protein
      stains used in this study successfully enhanced impressions in blood on light
      coloured fabrics, background staining caused interference on natural fabrics.
      Enhancement on dark coloured fabrics was only achieved using fluorescent protein
      stains, as non-fluorescent protein stains provided poor contrast. A further
      comparison was performed with commercially available protein staining solutions
      and solutions prepared within the laboratory from the appropriate chemicals. Both
      solutions performed equally well, though it is recommended to use freshly
      prepared solutions whenever possible.

PMID- 21889107
TI  - Chemical enhancement of footwear impressions in blood on fabric - part 2:
      peroxidase reagents.
AB  - This study investigates the optimisation of peroxidase based enhancement
      techniques for footwear impressions made in blood on various fabric surfaces.
      Four different haem reagents: leuco crystal violet (LCV), leuco malachite green
      (LMG), fluorescein and luminol were used to enhance the blood contaminated
      impressions. The enhancement techniques in this study were used successfully to
      enhance the impressions in blood on light coloured surfaces, however, only
      fluorescent and/or chemiluminescent techniques allowed visualisation on dark
      coloured fabrics, denim and leather. Luminol was the only technique to enhance
      footwear impressions made in blood on all the fabrics investigated in this study.

PMID- 21889108
TI  - A statistical methodology for the comparison of blue gel pen inks analyzed by
      laser desorption/ionization mass spectrometry.
AB  - A statistical methodology for the objective comparison of LDI-MS mass spectra of
      blue gel pen inks was evaluated. Thirty-three blue gel pen inks previously
      studied by RAMAN were analyzed directly on the paper using both positive and
      negative mode. The obtained mass spectra were first compared using relative areas
      of selected peaks using the Pearson correlation coefficient and the Euclidean
      distance. Intra-variability among results from one ink and inter-variability
      between results from different inks were compared in order to choose a
      differentiation threshold minimizing the rate of false negative (i.e. avoiding
      false differentiation of the inks). This yielded a discriminating power of up to
      77% for analysis made in the negative mode. The whole mass spectra were then
      compared using the same methodology, allowing for a better DP in the negative
      mode of 92% using the Pearson correlation on standardized data. The positive mode
      results generally yielded a lower differential power (DP) than the negative mode
      due to a higher intra-variability compared to the inter-variability in the mass
      spectra of the ink samples.

PMID- 21889109
TI  - Sampling and statistical considerations for the Suchey-Brooks method for pubic
      bone age estimation: implications for regional comparisons.
AB  - Although the Suchey-Brooks (SB) system is currently the most widely used method
      for age-at-death estimation from the pubic bone, the system continues to evolve
      through stepwise improvements. Since the system was developed from a pubic bone
      sample derived mainly from North Americans, it is unclear how well it performs on
      populations from other continents. During the last decade, studies of the SB
      system on pubic bone samples from local populations in Europe and Asia have
      indicated regional differences in the relationship between age and pubic bone
      development. However, these studies have for the most part followed different
      research protocols, which make comparisons between their results less meaningful.
      It would be most useful if future regional analysis of the SB system were done in
      a rigorous and uniform fashion, following standard procedures. In this paper,
      sampling and statistical considerations are outlined that hopefully will help to
      standardize research on the SB system.

PMID- 21889110
TI  - Estimation of postmortem interval using an electric impedance spectroscopy
      technique: a preliminary study.
AB  - The objective of this study was to develop a rapid method for the estimation of
      postmortem interval (PMI) using electric impedance spectroscopy. Postmortem rat
      spleens were studied at 10 degrees C, 20 degrees C, and 30 degrees C; The results
      obtained demonstrated that postmortem interval negatively correlated with the
      absolute value of Im Z(//) (capacitive reactance component) in electrical
      impedance. This suggests that electric impedance spectroscopy may be a sensitive
      tool to determine the postmortem interval.

PMID- 21889111
TI  - Are UK undergraduate Forensic Science degrees fit for purpose?
AB  - In October 2009 Skills for Justice published the social research paper 'Fit for
      purpose?: Research into the provision of Forensic Science degree programmes in UK
      Higher Education Institutions.' The research engaged employers representing 95%
      of UK Forensic Science providers and 79% of UK universities offering Forensic
      Science or Crime Scene degree programmes. In addition to this, the research
      collected the views of 430 students studying these degrees. In 2008 there were
      approximately 9000 people working in the Forensic Science sector in the UK. The
      research found that the numbers of students studying Forensic Science or Crime
      Scene degrees in the UK have more than doubled since 2002-03, from 2191 in to
      5664 in 2007-08. Over the same period there were twice as many females as males
      studying for these degrees. The research concluded that Forensic Science degree
      programmes offered by UK universities were of a good quality and they provided
      the student with a positive learning experience but the content was not relevant
      for Forensic Science employers. This echoed similar research by the former
      Government Department for Innovation, Universities and Skills on graduates from
      wider science, technology, engineering and mathematics degree programmes. The
      research also found that 75% of students studying Forensic Science or Crime Scene
      degrees expected to have a career in the Forensic Science sector, meaning that
      ensuring these courses are relevant for employers is a key challenge for
      universities. This paper reflects on the original research and discusses the
      implications in light of recent government policy.

PMID- 21889112
TI  - Development of biological standards for the quality assurance of presumptive
      testing reagents.
AB  - Forensic scientists periodically check working test reagents with known or
      standards to verify that the presumptive testing reagents are working properly.
      Often times, this is done with a neat body fluid such as blood or saliva that is
      dried onto a swab and kept in a freezer. The problem with this practice is that a
      degrading test reagent, for example acid phosphatase testing reagent, may test
      positive on a neat standard but miss a weak semen stain from a case. To ensure
      that presumptive testing reagents are working properly, a series of "weak"
      standards have been developed for the testing of acid phosphatase, amylase,
      creatinine and hemoglobin. The preparation and use of these biological standards
      will be discussed.

PMID- 21889113
TI  - Development and validation of a clinical prediction model to estimate the
      probability of malignancy in solitary pulmonary nodules in Chinese people.
AB  - INTRODUCTION: This study evaluated the clinical factors affecting the probability
      of malignancy of solitary pulmonary nodules (SPNs) using multivariate logistic
      regression analysis. A clinical prediction model was subsequently developed to
      estimate the probability of malignancy. This model was then validated. METHODS:
      Medical records from 371 patients (197 men, 174 women) with a pathologic
      diagnosis of SPN made between January 2000 and September 2009, were reviewed.
      Clinical data were collected to estimate the independent predictors of malignancy
      of SPN with multivariate analysis. A clinical prediction model was subsequently
      created. Between October 2009 and March 2010, data from an additional 62 patients
      with a pathologic diagnosis of SPN were used to validate this clinical prediction
      model. The model was also compared with two previously described models. RESULTS:
      Median patient age was 57.1 years old. Fifty-three percent of the nodules were
      malignant and 46% were benign. Logistic regression analysis identified six
      clinical characteristics (age, diameter, border, calcification, spiculation, and
      family history of tumor) as independent predictors of malignancy in patients with
      SPN. The area under the receiver operating characteristic (ROC) curve for our
      model (0.89; 50% confidence interval [CI], 0.78-0.99) was higher than those
      generated using another two reported models. In our model, sensitivity was 92.5%,
      specificity was 81.8%,positive predictive value was 90.2%, and negative
      predictive value was 85.7%). CONCLUSIONS: Age of the patient, diameter, border,
      calcification, spiculation, and family history of tumors were independent
      predictors of malignancy in patients with SPN. Our prediction model was more
      accurate than the two existing models and was sufficient to estimate malignancy
      in patients with SPN.

PMID- 21889114
TI  - Association of copy number loss of CDKN2B and PTCH1 with poor overall survival in
      patients with pulmonary squamous cell carcinoma.
AB  - BACKGROUND AND PURPOSE: Although lung cancer is the leading cause of cancer
      deaths worldwide, reliable markers allowing prediction of patient survival at the
      time of initial diagnosis are still lacking. Copy number alterations (CNAs) in
      tumor tissue DNA have been associated with tumorigenesis and malignant
      progression. We aimed at identification of gene-level CNAs with prognostic value
      for survival in pulmonary squamous cell carcinoma (SCC). METHODS: The CNA status
      of a panel of 44 genes was analyzed by high-resolution array comparative genomic
      hybridization (CGH) in 49 SCC samples. Overall survival information (median
      follow-up, 40 months) for the patients was collected and used to assess outcome
      correlations with gene CNAs. RESULTS: Survival analysis showed that both CDKN2B
      loss and PTCH1 loss were associated with poor survival (both P < .001, log-rank
      test). Multivariate Cox analysis, including CDKN2B loss and PTCH1 loss as well as
      age, sex, cigarette smoking status, tumor size, tumor differentiation, and TNM
      stage showed that CDKN2B loss (hazard ratio [HR], 17.88; 95% confidence interval
      [CI], 4.40-72.67; P < .001) and PTCH1 loss (HR, 10.81; 95% CI, 1.92-60.98; P =
      .007) were independent prognostic factors for poor survival. In addition the
      PTCH1 loss was more frequently found in moderately or poorly differentiated
      tumors than in well-differentiated tumors (P = .007). CONCLUSION: These findings
      suggest that 2 genes of loss, CDKN2B and PTCH1, are associated with poor overall
      survival in patients with SCC of the lung and may be useful as prognostic
      markers.

PMID- 21889115
TI  - Impact of apolipoprotein E4-cerebrospinal fluid beta-amyloid interaction on
      hippocampal volume loss over 1 year in mild cognitive impairment.
AB  - BACKGROUND: The majority of studies relating amyloid pathology with brain volumes
      have been cross-sectional. Apolipoprotein E4 (APOE E4), a genetic risk factor for
      Alzheimer's disease, is also known to be associated with hippocampal volume loss.
      No studies have considered the effects of amyloid pathology and APOE E4 together
      on longitudinal volume loss. METHODS: We evaluated whether an abnormal level of
      cerebrospinal fluid beta-amyloid (CSF Abeta) and APOE E4 carrier status were
      independently associated with greater hippocampal volume loss over 1 year. We
      then assessed whether APOE E4 status and CSF Abeta acted synergistically, testing
      the significance of an interaction term in the regression analysis. We included
      297 participants: 77 cognitively normal, 144 with mild cognitive impairment
      (MCI), and 76 with Alzheimer's disease. RESULTS: An abnormal CSF Abeta level was
      found to be associated with greater hippocampal volume loss over 1 year in each
      group. APOE E4 was associated with hippocampal volume loss only in the
      cognitively normal and MCI groups. APOE E4 carriers with abnormal CSF Abeta in
      the MCI group acted synergistically to produce disproportionately greater volume
      loss than noncarriers. CONCLUSION: Baseline CSF Abeta predicts progression of
      hippocampal volume loss. APOE E4 carrier status amplifies the degree of
      neurodegeneration in MCI. Understanding the effect of interactions between
      genetic risk and amyloid pathology will be important in clinical trials and our
      understanding of the disease process.

PMID- 21889116
TI  - Neuropsychiatric symptoms in Alzheimer's disease.
AB  - Neuropsychiatric symptoms (NPS) are core features of Alzheimer's disease and
      related dementias. Once thought to emerge primarily in people with late-stage
      disease, these symptoms are currently known to manifest commonly in very early
      disease and in prodromal phases, such as mild cognitive impairment. Despite
      decades of research, reliable treatments for dementia-associated NPS have not
      been found, and those that are in widespread use present notable risks for people
      using these medications. An Alzheimer's Association Research Roundtable was
      convened in the spring of 2010 to review what is known about NPS in Alzheimer's
      disease, to discuss classification and underlying neuropathogenesis and
      vulnerabilities, and to formulate recommendations for new approaches to tailored
      therapeutics.

PMID- 21889118
TI  - [Comment on: Nonsexually transmitted acute ulcer of the vulva associated with
      influenza A virus infection].

PMID- 21889119
TI  - Reversible nutritional hypogonadism in a 22-year-old man.

PMID- 21889117
TI  - Dementia and Alzheimer's disease: a new direction.The 2010 Jay L. Foster Memorial
      Lecture.
AB  - BACKGROUND: The modern era of Alzheimer's disease (AD) research began in the
      early 1980s with the establishment of AD research centers and expanded research
      programs at the National Institute on Aging. METHODS: Over the past 30 years,
      there has been success in defining criteria for AD and dementia, association of
      important genetic disorders related to premature dementia in families, the
      association of apolipoprotein-E(4), and measurement of incidence and prevalence
      and selected risk factors. However, prevention and treatment have been elusive.
      RESULTS: The development of new technologies, especially magnetic resonance
      imaging, positron emission tomography to measure amyloid in vivo in the brain and
      glucose metabolism, cerebrospinal fluid examination, better genetic markers,
      large-scale longitudinal epidemiology studies, and preventive clinical trials has
      rapidly begun a new era of research that offers opportunities to better
      understand etiology, that is, determinants of amyloid biology in the brain,
      neurofibrillary tangles, synaptic loss, and dementia. CONCLUSIONS: There are
      three major hypotheses related to dementia: amyloid deposition and secondary
      synaptic loss as a unique disease, vascular injury, and "aging." New research
      must be hypothesis-driven and lead to testable approaches for treatment and
      prevention.

PMID- 21889120
TI  - Benefits and risks of expectant management of severe preeclampsia at less than 26
      weeks gestation: the impact of gestational age and severe fetal growth
      restriction.
AB  - OBJECTIVE: To determine maternal and perinatal outcome in women with severe
      preeclampsia at <26 weeks according to gestational age at the onset of expectant
      management and the presence of severe fetal growth restriction (<5th percentile).
      STUDY DESIGN: Fifty-one patients (53 fetuses; 2 twins) were retrospectively
      studied. RESULTS: Median prolongation was 7 days (2-55). Maternal morbidity rate
      was 43%. Perinatal survival rate was 42%. Severe fetal growth restriction
      complicated 17 fetuses (33%). There were no perinatal survivors in those managed
      at <24 weeks (n = 12). For those at 24-24(6/7) and 25-25(6/7) weeks, the
      perinatal survival rates were 50% and 57%, respectively, and in the presence of
      severe fetal growth restriction 0% and 30%, respectively. CONCLUSION: Perinatal
      outcome in severe preeclampsia in the midtrimester is dependent on gestational
      age and/or the presence of severe fetal growth restriction. Given the high
      maternal morbidity and the extremely low perinatal survival rates, we do not
      recommend expectant management before 24 weeks and/or in those with severe fetal
      growth restriction at any gestational age <26 weeks.

PMID- 21889122
TI  - Preventing Low Birthweight: 25 years, prenatal risk, and the failure to reinvent
      prenatal care.
AB  - In 2010, Preventing Low Birthweight celebrated it 25th anniversary. The report,
      one of the most influential policy statements ever issued regarding obstetric
      health care delivery, linked prenatal care to a reduction in low birthweight
      (LBW). Medicaid coverage for prenatal care services was subsequently expanded and
      resulted in increased prenatal care utilization. However, the rate of LBW failed
      to decrease. This well-intentioned expansion of prenatal care services did not
      change the structure of prenatal care. A single, standardized prenatal care
      model, largely ineffective in the prevention of LBW, was expanded to a
      heterogeneous group of patients with a variety of medical and psychosocial risk
      factors. Reinventing prenatal care as a flexible model, with content, frequency,
      and timing tailored to maternal and fetal risk, may improve adverse birth
      outcomes. Risk-appropriate prenatal care may improve the effectiveness of
      prenatal care for high-risk patients and the efficiency of prenatal care delivery
      for low-risk patients.

PMID- 21889124
TI  - A highly efficient deprotection of the 2,2,2-trichloroethyl group at the anomeric
      oxygen of carbohydrates.
AB  - Commercially available zinc dust in the presence of ammonium chloride in
      acetonitrile at reflux removes the 2,2,2-trichloroethyl (TCE) group at anomeric
      centers with excellent yields (>95%) in short reaction times. This present method
      is easily implemented on substrates containing acyl and benzyl groups and large
      scale reactions also proceed in high yield.

PMID- 21889123
TI  - Emergence of functional spinal delta opioid receptors after chronic ethanol
      exposure.
AB  - BACKGROUND: The delta opioid receptor (DOR) is a promising target to treat
      multiple indications, including alcoholism, anxiety, and nonmalignant pain. The
      potential of the DORs has been underappreciated, in part, due to relatively low
      functional expression of these receptors in naive states. However, chronic
      exposure to stress, opioids, and inflammation can induce a redistribution of DORs
      to the cell surface where they can be activated. Previously, DORs were shown to
      be selectively/exclusively present in spinal cord circuits mediating mechanical
      sensitivity but not those mediating thermal nociception under naive conditions.
      METHODS: We spinally administered DOR and mu opioid receptor (MOR) selective
      agonists ([D-Pen2,D-Pen5]-Enkephalin, deltorphin II, SNC80, and DAMGO) and
      antagonists (naltriben and CTAP) and determined thermal antinociception and
      mechanical sensitivity in wild-type mice or mice with a genetic disruption of DOR
      or MOR. Thermal antinociception was measured using a radiant heat tail-flick
      assay; mechanical sensitivity was measured using von Frey filaments. Dose
      response curves were generated in naive mice and mice exposed to ethanol in a
      model of voluntary consumption. RESULTS: We show that prolonged exposure to
      ethanol can promote an upregulation of functional DORs in the spinal cord in
      thermal pain-mediating circuits but not in those mediating mechanical
      sensitivity. The upregulated DORs either modulate MOR-mediated analgesia through
      convergence of circuits or signal transduction pathways and/or interact directly
      with MORs to form a new functional (heteromeric) unit. CONCLUSIONS: Our findings
      suggest that DORs could be a novel target in conditions in which DORs are
      redistributed.

PMID- 21889125
TI  - Phosphorous pentoxide mediated synthesis of 5-HMF in ionic liquid at low
      temperature.
AB  - A convenient, mild and environment-friendly dehydration reaction of fructose in
      ionic liquid using phosphorous pentoxide (P(2)O(5)) has been investigated. The
      acidic nature of P(2)O(5) along with its hygroscopic properties has been
      successfully utilized to afford 81.2% yield of 5-hydroxymethylfurfural (5-HMF) at
      50 degrees C in 60 mins. Phosphoric acid yielded remarkably less 5-HMF even at
      higher temperature and longer reaction times. The reaction was optimized by
      varying different parameters and the results indicated that no rehydration
      products, such as levulinic acid or formic acid, were formed.

PMID- 21889126
TI  - Atorvastatin ameliorates experimental autoimmune neuritis by decreased Th1/Th17
      cytokines and up-regulated T regulatory cells.
AB  - Statins have anti-inflammatory and immune-regulating properties. To investigate
      the effects of atorvastatin on experimental autoimmune neuritis (EAN), an animal
      model of Guillain-Barre syndrome (GBS), atorvastatin was administered to Lewis
      rats immunized with bovine peripheral myelin in complete Freund's adjuvant. We
      found that atorvastatin ameliorated the clinical symptoms of EAN, decreased the
      numbers of inflammatory cells as well as IFN-gamma(+) and IL-17(+) cells in
      sciatic nerves, decreased the CD80 expression and increased the number of
      CD25(+)Foxp3(+) cells in mononuclear cells (MNC), and decreased the levels of IFN
      gamma in MNC culture supernatants. These data provide strong evidence that
      atorvastatin can act as an inhibitor in EAN by inhibiting the immune response of
      Th1 and Th17, decreasing the expression of co-stimulatory molecule, and up
      regulating the number of T regulatory cells. These data demonstrated that statins
      could be used as a therapeutic strategy in human GBS in future.

PMID- 21889127
TI  - Pattern of MHC class I and immune proteasome expression in Walker 256 tumor
      during growth and regression in Brattleboro rats with the hereditary defect of
      arginine-vasopressin synthesis.
AB  - Dynamics of the expression of MHC class I, immune proteasomes and proteasome
      regulators 19S, PA28, total proteasome pool and proteasome chymotrypsin-like
      activity in Walker 256 tumor after implantation into Brattleboro rats with the
      hereditary defect of arginine-vasopressin synthesis was studied. The tumor growth
      and regression in Brattleboro rats were accompanied by changes in the proteasome
      subunit level unlike the tumor growth in WAG rats with normal expression of
      arginine-vasopressin gene. In the tumor implanted into Brattleboro rats the
      immune proteasome level was maximal between days 14 and 17, when the tumor
      underwent regression. Conversely, the expression of proteasome regulators tended
      to decrease during this period. Immune proteasomes are known to produce antigen
      epitopes for MHC class I to be presented to CD8+ T lymphocytes. Enhanced
      expression of immune proteasomes coincided with the recovery of MHC class I
      expression, suggesting the efficient presentation of tumor antigens in
      Brattleboro rats.

PMID- 21889128
TI  - Antigen adsorbed calcium phosphate nanoparticles stimulate both innate and
      adaptive immune response in fish, Labeo rohita H.
AB  - Calcium phosphate nanoparticles as an antigen/protein delivery was explored in a
      fish model Labeo rohita H. S-layer protein (of Aeromonas hydrophila) adsorbed on
      nano sized calcium phosphate particles elicited both innate and adaptive immune
      parameters which persisted up to 63 days of post immunization through parenteral
      immunization and gave cross protections.

PMID- 21889129
TI  - Reduced efficacy of multiple doses of CpG-matured dendritic cell tumor vaccine in
      an experimental model.
AB  - CpG motifs have been advanced as agents that stimulate the maturation of DCs for
      immunotherapy. The present study tested the hypothesis that multiple doses of CpG
      matured DC vaccine would be efficacious for complete eradication of
      experimentally-induced tumor. Accordingly, WEHI164 cells were implanted
      subcutaneously in the flank of BALB/c mice. During DC culture, tumor lysate was
      added to immature DCs followed by addition of CpG or non-CpG control 4-6h later.
      A total of three doses of CpG or non-CpG control-matured DCs were injected around
      tumors. The results showed that multiple doses of CpG-matured DCs led to
      considerable decrease in cytotoxicity of lymphocytes and significantly increased
      tumor growth rate compared to a single dose. Further, mice which received three
      doses of the vaccine also displayed significant FoxP3 in tumor tissue. In
      conclusion, multiple doses of CpG-matured DCs exhibited decreased anti-tumor
      immunity in association with increased expression of FoxP3.

PMID- 21889130
TI  - The TLR7/8 ligand resiquimod targets monocyte-derived dendritic cell
      differentiation via TLR8 and augments functional dendritic cell generation.
AB  - Imidazoquinolone compounds, such as resiquimod are Toll-like receptor (TLR) 7/8
      ligands representing novel immune response modifiers undergoing clinical testing.
      Resiquimod has been reported to modulate conventional human monocyte-derived DC
      (moDC) differentiation, but the role of TLR7 and TLR8 is unclear. We directly
      dissected the TLR7- and TLR8-dependency by employing selective TLR7 ligands and
      resiquimod-coculture experiments with inhibitory oligonucleotides (iODN)
      suppressing TLR7, TLR7+8 or TLR7+8+9. Selective TLR7 ligands did not affect
      conventional moDC differentiation as analyzed by CD14/CD1a expression. iODN
      experiments confirmed that resiquimod's effects during DC differentiation were
      antagonized only with TLR8 iODNs. Direct comparison of resiquimod DC with TLR7-
      and control-DC revealed significantly higher T-cell costimulatory molecule and
      MHC class II expression. Resiquimod DC promoted significantly stronger allogeneic
      T-cell proliferation and stronger naive CD4(+) T-cell proliferation. These
      results indicate the relevance of TLR8 for human monocyte-derived DC
      differentiation and maturation and may be relevant for clinical trials employing
      resiquimod.

PMID- 21889131
TI  - Comparative binding of soluble fragments (derCD23, sCD23, and exCD23) of
      recombinant human CD23 to CD21 (SCR 1-2) and native IgE, and their effect on IgE
      regulation.
AB  - IgE, responsible for type I hypersensitivities, is regulated by interactions
      between its receptor, CD23, and co-receptor CD21. To examine comparative binding
      of recombinant human CD21 SCR 1-2 and native human IgE to CD23 plus the effect of
      CD23 on IgE production, we engineered recombinant soluble human CD23 fragments;
      (1) derCD23, (2) sCD23 and (3) exCD23, formed in vivo by proteolysis. SPR
      analysis revealed a progressive increment in affinity of soluble fragments for
      IgE, upon increasing length of CD23 "stalk" domain, exCD23>sCD23>derCD23. Soluble
      CD23 fragments and their oligomeric state are shown to fine-tune the immune
      response. Oligomers appear more important in enhancing IgE synthesis and monomers
      lacking the tail residues fail to bind CD21 yet bind membrane IgE and down
      regulate IgE synthesis. Co-ligation of membrane IgE and CD21 through soluble CD23
      monomers is disturbed. This study supports anti-allergic therapies involving
      stabilizing membrane CD23, or preventing shedding of soluble CD23.

PMID- 21889132
TI  - Mirrors, mirrors on the wall...the ubiquitous multiple reflection error.
AB  - Participants decided when somebody, Janine, could see their face in a horizontal
      row of adjacent mirrors mounted flat on the same wall. They saw real mirrors and
      a shop-dummy representing Janine. Such coplanar mirrors reflect different, non
      overlapping areas of a scene. However, almost everybody made an unexpected error:
      they claimed that Janine would see her face reflected in multiple mirrors
      simultaneously. They therefore responded as if each mirror showed similar
      information and thus grossly overestimated how much each mirror revealed. Further
      studies established that this multiple reflection error also occurred for
      vertical rows of mirrors and for different areas of a single, large mirror. The
      error was even common if the participant themselves sat in front of a set of
      covered-up mirrors and indicated where they would be able to see their own
      reflection. In the latter case, people often made multiple reflection errors
      despite having seen all the mirrors uncovered immediately before they responded.
      People's gross overestimation of how much of a scene a mirror reflects and their
      inability to learn to correct this false belief explains why, despite a
      lifetime's experience of mirrors, they incorrectly think they will see themselves
      in all nearby mirrors.

PMID- 21889133
TI  - Impaired visual sensitivity within the ipsilesional hemifield following parietal
      lobe damage.
AB  - The parietal cortex is considered to be part of a network of brain areas that
      modulates competitive interactions between targets and irrelevant distracters in
      early visual cortex, however there is currently little causal evidence to support
      this in human observers. It is also unclear as to whether parietal influences on
      visual perception in humans are limited to the contralesional hemispace or
      whether a unilateral lesion affects visual sensitivity bilaterally. Here we
      examined visual sensitivity in two patients with spatial neglect and extinction
      arising primarily from left-parietal damage. We used a sensitive psychophysical
      task based on those previously used to demonstrate loss of stimulus selection
      after lesions to extrastriate cortex. Observers discriminated the orientation of
      a lateralized suprathreshold target grating that appeared alone or in the context
      of nearby salient disc distracters. For parietal patients, target sensitivity
      within both the contralesional and ipsilesional fields was compromised by the
      presence of distracters. Conversely, healthy matched controls were unaffected by
      distracters. These results indicate that parietal cortex damage can influence
      visual perception within both the ipsi- as well as the contralesional field.

PMID- 21889134
TI  - Relative size of numerical magnitude induces a size-contrast effect on the grip
      scaling of reach-to-grasp movements.
AB  - Previous research found that quantitative information labelled on target objects
      of grasping movement modulates grip apertures. While the interaction between
      numerical cognition and sensorimotor control may reflect a general representation
      of magnitude underpinned by the parietal cortex, the nature of this embodied
      cognitive processing remains unclear. In the present study, we examined whether
      the numerical effects on grip aperture can be flexibly modulated by the relative
      magnitude between numbers under a context, which suggests a trial-by-trial
      comparison mechanism to underlie this effect. The participants performed visual
      open-loop grasping towards one of two adjacent objects that were of the same
      physical size but labelled with different Arabic digits. Analysis of
      participants' grip apertures revealed a numerical size-contrast effect, in which
      the same numerical label (i.e., 5) led to larger grip apertures when it was
      accompanied by a smaller number (i.e., 2) than by a larger number (i.e., 8). The
      corrected grip aperture over the time course of movement showed that the
      numerical size-contrast effect remained significant throughout the grasping
      movement, despite a trend of gradual dissipation. Our findings demonstrated that
      interactions between number and action critically depend on the size-contrast of
      magnitude information in the context. Such a size-contrast effect might result
      from a general system, which is sensitive to relative magnitude, for different
      quantity domains. Alternatively, the magnitude representations of numbers and
      action might be processed separately and interact at a later stage of motor
      programming.

PMID- 21889135
TI  - Esophageal foreign-body impactions: epidemiology, time trends, and the impact of
      the increasing prevalence of eosinophilic esophagitis.
AB  - BACKGROUND: The epidemiology of esophageal foreign-body impaction (EFBI) is
      poorly described, and the impact of the increasing prevalence of eosinophilic
      esophagitis (EoE) on this is unknown. OBJECTIVE: To assess the characteristics of
      patients with EFBI, to determine whether EFBI cases increased in proportion to
      EoE cases, and to identify predictors of EFBI. DESIGN: Retrospective study.
      SETTING: Tertiary care center. PATIENTS: Cases of EFBI from 2002 to 2009 were
      identified by querying billing, clinical, and endoscopy databases for the
      International Classification of Diseases, 9th Revision, Clinical Modification
      code 935.1, "foreign body in the esophagus." Charts were reviewed to confirm EFBI
      and to extract pertinent data. Cases of EoE were defined per guidelines. RESULTS:
      Of 548 patients with EFBI (59% male, 68% white, bimodal age distribution), 482
      (88%) required a procedure, 347 (63%) had food impactions, and 51 (9%) had EoE.
      EFBIs increased over the study time frame, and the number of EGDs performed for
      EFBI nearly quadrupled. Increasing diagnosis of EoE did not fully account for
      this trend, but only 27% of patients who underwent EGD had esophageal biopsies.
      Of patients who underwent biopsy, 46% had EoE. EoE was the strongest predictor of
      multiple EFBIs (odds ratio 3.5; 95% CI, 1.8-7.0). LIMITATIONS: Retrospective,
      single-center study. CONCLUSIONS: The number of EGDs performed for EFBI has
      increased dramatically at our center, but increasing EoE prevalence only
      partially explains this trend. Because only a minority of EFBI patients underwent
      biopsies and because nearly half of those who did undergo biopsy had EoE, the
      incidence of EoE may be substantially underestimated. Physician education is
      needed to increase the proportion of subjects with EFBI who undergo biopsies.

PMID- 21889137
TI  - Participation by experienced endoscopy nurses increases the detection rate of
      colon polyps during a screening colonoscopy: a multicenter, prospective,
      randomized study.
AB  - BACKGROUND: No reported prospective, randomized study has evaluated the impact of
      an endoscopy nurse participating as a second observer during colonoscopy.
      OBJECTIVE: To determine whether the participation of an endoscopy nurse enhanced
      the polyp detection rate (PDR) and adenoma detection rate (ADR) during screening
      colonoscopy. DESIGN: Multicenter, prospective, randomized study. SETTING:
      Academic hospitals. PATIENTS: A total of 844 consecutive patients undergoing
      screening colonoscopy. INTERVENTIONS: Single observation by colonoscopist or dual
      observation by colonoscopist and endoscopy nurse during colonoscope withdrawal.
      MAIN OUTCOME MEASUREMENTS: PDR and ADR. RESULTS: No significant difference in
      patient demographic data, adequacy of bowel preparation, or mean withdrawal time
      was observed between the 2 groups. In total, 1153 polyps, including 762 adenomas,
      were detected in 791 patients. Seven nonpolypoid, depressed neoplastic lesions (0
      IIc or combined types) were only detected in the dual observation group. A
      multivariate analysis revealed that experienced (>= 2 years) endoscopy nurse
      participation significantly increased the PDR and ADR compared with those in the
      single observation group by a colonoscopist alone (adjusted odds ratio [OR] 1.58
      [95% CI, 1.07-2.32]; adjusted OR 1.47 [95% CI, 1.01-2.12], respectively).
      Additionally, the PDR was significantly higher in the dual-observation group with
      fellows (<500 colonoscopies) and an experienced endoscopy nurse versus that in
      the single observation group (adjusted OR 2.07 [95% CI, 1.15-3.74]). There was no
      significant benefit of experienced nurse participation in the subgroup with
      experienced colonoscopists. LIMITATIONS: Absence of colonoscopist blinding.
      CONCLUSIONS: Experienced endoscopy nurse participation increased the PDR and ADR
      during screening colonoscopy. However, the benefit of participation by
      experienced nurses appears to be exclusively with inexperienced colonoscopists.

PMID- 21889136
TI  - Clinical impact of EUS-guided Trucut biopsy results on decision making for
      patients with gastric subepithelial tumors >= 2 cm in diameter.
AB  - BACKGROUND: Preoperative pathologic diagnosis of a gastric subepithelial tumor
      (SET) may improve clinical decision making. However, the clinical impact of EUS
      guided Trucut biopsy (EUS-TCB) data on decision making in patients with a gastric
      SET has not been assessed. OBJECTIVE: To evaluate the impact of EUS-TCB
      information on the clinical management of patients with a gastric SET. DESIGN:
      Retrospective review of prospectively collected data. SETTING: Tertiary referral
      center. PATIENTS: Sixty-five patients with gastric SETs 2 cm or larger in
      diameter. INTERVENTION: EUS-TCB. MAIN OUTCOME MEASUREMENTS: The number of
      patients for whom treatment plans were changed because of EUS-TCB results.
      RESULTS: Nine SETs were not punctured by the TCB needle because of technical
      problems, and we were unable to obtain adequate subepithelial tissue from 19
      SETs. Treatment plans were changed for 18 of 65 patients (27.7%). The changes
      were avoiding unnecessary resection (7 benign SETs >= 3 cm in diameter),
      scheduling for definitive treatment (6 GI stromal tumors and 1 carcinoid tumor),
      and modifying the surgical field (3 large GI stromal tumors and 1 carcinoma).
      When we assessed treatment plans relative to tumor location, we found that
      avoiding unnecessary resection was associated with the presence of cardiac SETs.
      LIMITATIONS: Retrospective study with a small number of patients. CONCLUSIONS:
      EUS-TCB changed or influenced management decisions in 18 of 65 patients (27.7%)
      with gastric SETs. Patients could receive proper and tailored surgery, medical
      treatment, or surveillance according to size and location of SETs with EUS-TCB.

PMID- 21889138
TI  - Successful management of perforation during cystogastrostomy with an esophageal
      fully covered metallic stent placement.

PMID- 21889139
TI  - EUS-guided transesophageal treatment of gastric fundal varices with combined
      coiling and cyanoacrylate glue injection (with videos).
AB  - BACKGROUND: There have been numerous reports of glue embolization after
      endoscopic cyanoacrylate (CYA) glue treatment of gastric fundal varices (GFV),
      with some cases fatal. Coils with attached synthetic fibers may decrease or
      eliminate this risk and may decrease the amount of CYA needed to achieve
      obliteration. OBJECTIVE: Assess the feasibility, safety, and outcomes of
      transesophageal EUS-guided therapy of GFV with combined coil and CYA injection.
      DESIGN: Retrospective query of a prospectively maintained database. SETTING:
      Tertiary care medical center. PATIENTS: Patients with hemorrhage from large GFV.
      INTERVENTION: A standardized approach by using EUS-guided coil and CYA treatment.
      MAIN OUTCOMES MEASUREMENTS: Hemostasis, rebleeding rate, complications. RESULTS:
      Thirty patients with GFV were treated between March 2009 and January 2011. At
      index endoscopy, 2 patients had active hemorrhage and 14 had stigmata of recent
      hemorrhage. EUS-guided transesophageal treatment of GFV was successful in all.
      Mean number of GFV treated was 1.3 per patient, and the mean volume of 2-octyl
      CYA injected was 1.4 mL per varix. Hemostasis of acute bleeding was 100%. Among
      24 patients with a mean follow-up of 193 days (range 24-589 days), GFV were
      obliterated after a single treatment session in 23 (96%). Rebleeding occurred in
      4 patients (16.6%), with none attributed to GFV. There were no procedure-related
      complications and no symptoms or signs of CYA embolization. LIMITATIONS: Single
      center, pilot study. CONCLUSION: Transesophageal EUS-guided coil and CYA
      treatment of GFV is feasible and deserves further study to determine whether this
      novel approach can improve safety and efficacy over standard endoscopic injection
      of CYA alone.

PMID- 21889140
TI  - On an LAS-integrated soft PLC system based on WorldFIP fieldbus.
AB  - Communication efficiency is lowered and real-time performance is not good enough
      in discrete control based on traditional WorldFIP field intelligent nodes in case
      that the scale of control in field is large. A soft PLC system based on WorldFIP
      fieldbus was designed and implemented. Link Activity Scheduler (LAS) was
      integrated into the system and field intelligent I/O modules acted as networked
      basic nodes. Discrete control logic was implemented with the LAS-integrated soft
      PLC system. The proposed system was composed of configuration and supervisory sub
      systems and running sub-systems. The configuration and supervisory sub-system was
      implemented with a personal computer or an industrial personal computer; running
      subsystems were designed and implemented based on embedded hardware and software
      systems. Communication and schedule in the running subsystem was implemented with
      an embedded sub-module; discrete control and system self-diagnosis were
      implemented with another embedded sub-module. Structure of the proposed system
      was presented. Methodology for the design of the sub-systems was expounded.
      Experiments were carried out to evaluate the performance of the proposed system
      both in discrete and process control by investigating the effect of network data
      transmission delay induced by the soft PLC in WorldFIP network and CPU workload
      on resulting control performances. The experimental observations indicated that
      the proposed system is practically applicable.

PMID- 21889141
TI  - Stabilization of fatigue fractures of the dorsal pelvis with a trans-sacral bar.
      Operative technique and outcome.
AB  - INTRODUCTION: Due to ageing of our population the number of fatigue fractures of
      the pelvic ring is steadily growing. These fractures are often treated with bed
      rest but may result in a disabling immobility with severe pain. An operative
      treatment is an option in these cases. The aim of operative treatment is bony
      healing obtained by stable fixation giving back to the patient's previous
      mobility. Optimal surgical treatment is currently under debate. Sacroiliac screw
      fixation and sacroplasty are used for stabilization of the dorsal pelvis. Due to
      the technique and the low density of spongious sacral bone, no or only low
      compression in the fracture site is obtained, which may inhibit bony healing. The
      trans-sacral bar compression osteosynthesis is presented as an alternative
      procedure. We present the outcome of 11 patients, who were treated with this
      method. METHODS: The patient is placed in prone position on the operation table.
      Under image intensifier control, a 5mm threaded sacral bar is inserted through
      the body of S1 from the left to the right dorsal ilium. Nuts are placed over the
      bar achieving fracture compression. When anterior pelvic instability is present,
      an anterior osteosynthesis is also performed. Clinical and radiological outcome
      were evaluated one year after index surgery with different scoring systems.
      RESULTS: Eleven patients (9 F and 2 M) were treated between 2005 and 2010. The
      mean age of the patients was 73 years at time of operation. There were no
      mechanical complications. Postoperatively there was a temporary nerve palsy of L5
      in one case. The mean follow-up was 14 months. In all patients, a bony healing of
      the dorsal pelvic ring was achieved. Seven patients showed a major clinical
      improvement, in four patients a moderate. CONCLUSIONS: Trans-sacral bar
      osteosynthesis is a promising method for stabilization of fatigue fractures of
      the pelvic ring. Only with this method, a high interfragmentary compression is
      achieved, independent of the quality of the spongious bone of the sacral body.

PMID- 21889142
TI  - Allograft bone matrix versus synthetic bone graft substitutes.
AB  - Autologous bone is used very often in the treatment of fresh fractures, delayed
      unions and non-unions. Alternatives have included allografts and in recent years
      also demineralized bone matrix. The growing availability of good synthetic bone
      grafts and their advantages in safety and avoiding donor-site morbidity are the
      reasons that these products are being used more and more. There are on the market
      a wide variety of substitutes with different capabilities. Nevertheless
      autologous bone graft is still considered as the gold standard and will be
      discussed here in that context. Osteoconductive, osteogenic and osteoinductive
      products will also be classified and their advantages and disadvantages
      described.

PMID- 21889143
TI  - Incidence and predictors for the need for fasciotomy after extremity trauma.

PMID- 21889144
TI  - Opposite effects of pravastatin and atorvastatin on insulin sensitivity in the
      rat: role of vitamin D metabolites.
AB  - OBJECTIVE: Recent studies indicate that pravastatin improves whereas other
      statins impair glucose homeostasis in humans, but the underlying mechanisms are
      not clear. We examined the effect of pravastatin and atorvastatin on insulin
      sensitivity in a rat model. METHODS: Pravastatin (40 mg/kg/day) or atorvastatin
      (20mg/kg/day) were administered for 3 weeks and insulin sensitivity was assessed
      by measuring fasting plasma insulin, HOMA-IR, non-esterified fatty acids (NEFA)
      and glycerol levels, as well as by the hyperinsulinemic euglycemic clamp.
      RESULTS: Pravastatin had no effect on fasting insulin and HOMA-IR but
      significantly reduced plasma NEFA and glycerol levels and increased glucose
      infusion rate (GIR) during the hyperinsulinemic clamp. Increase in GIR induced by
      pravastatin was not abolished by NO synthase inhibitor, l-NAME, indicating that
      this effect did not result from the improvement of endothelial function.
      Atorvastatin increased fasting insulin, HOM-IR, NEFA and glycerol levels as well
      as reduced GIR. Statins had no effect on leptin, HMW adiponectin, resistin,
      visfatin, interleukin-6 and TNF-alpha. Pravastatin increased plasma
      concentrations of 25-hydroxy- and 1,25-dyhydroxyvitamin D(3) (25-OH-D(3) and 1,25
      (OH)(2)-D(3)), and its effect on insulin sensitivity was mimicked by exogenous
      1,25-(OH)(2)-D(3). Atorvastatin reduced plasma 25-OH-D(3) but had no effect on
      1,25-(OH)(2)-D(3). Decrease in insulin sensitivity induced by atorvastatin was
      not corrected by supplementation of vitamin D(3) despite normalization of plasma
      25-OH-D(3) level. CONCLUSIONS: Pravastatin and atorvastatin have opposite effects
      on insulin sensitivity and vitamin D(3) status. Pravastatin-induced increase in
      insulin sensitivity is mediated by elevation of 1,25-(OH)(2)-D(3). In contrast,
      atorvastatin-induced decrease in insulin sensitivity is independent of lowering
      25-OH-D(3).

PMID- 21889145
TI  - Lack of association between plasma PCSK9 and LDL-apoB100 catabolism in patients
      with uncontrolled type 2 diabetes.
AB  - OBJECTIVE: Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a post
      transcriptional inhibitor of LDL-receptor. In non-diabetic men, plasma PCSK9
      levels were found to be inversely correlated with low-density lipoprotein (LDL)
      apolipoprotein B100 (apoB) fractional catabolic rate (FCR). Here, we aimed to
      determine the effect of type 2 diabetes on the association between plasma PCSK9
      and FCR of LDL. METHODS: A kinetic study of LDL-apoB100, using stable isotopes,
      was performed in 38 individuals (20 men, 18 women) including 23 non-diabetic
      normolipidemic subjects and 15 patients with type 2 diabetes. RESULTS: In the non
      diabetic group, plasma PCSK9 was positively correlated with LDL-C (r=0.64,
      p=0.001), apoB (r=0.67, p<0.001), and inversely correlated with LDL-apoB FCR (r=
      0.61, p=0.002). In contrast, in type 2 diabetic patients, plasma PCSK9 was not
      associated with LDL-C, apoB and LDL-apoB FCR. However, the lack of association
      between PCSK9 and LDL-apoB FCR seemed to be limited to the patients with
      "uncontrolled" diabetes (HbA1c>7%) since a borderline significant negative
      correlation between PCSK9 and LDL FCR (r=-0.70, p=0.08) was retrieved in patients
      with HbA1c<=7%. In multivariate analysis, LDL-apoB FCR was independently
      associated with PCSK9 (p=0.001) and fasting glycaemia (log) (p=0.030) in the non
      diabetic population and with PCSK9 (p=0.040) and HbA1c (p=0.029) in diabetic
      patients. CONCLUSION: Our data indicate that both PCSK9 and glycaemia are
      independent factors influencing LDL catabolism. Plasma PCSK9 influences
      significantly the catabolism of LDL-apoB100 in individuals without diabetes, but
      not in patients with uncontrolled type 2 diabetes. Thus, the influence of
      diabetes on LDL-apoB FCR catabolism may overwhelm the influence of PCSK9.

PMID- 21889146
TI  - Comparison of risk factors for fatal stroke and ischemic heart disease: a
      prospective follow up of the health survey for England.
AB  - OBJECTIVES: The aim was to compare risk factors for stroke and ischemic heart
      disease (IHD) in a large general population cohort. METHODS: A prospective cohort
      of 82,380 participants (aged 55.4 [SD 14.2 yrs], 44.8% men) without known history
      of cardiovascular diseases (CVD) at baseline was pooled from ten years (1994
      2004) of the Health Survey for England. Study members were followed, on average,
      over 8 years for cause-specific mortality using linkage to national registers.
      RESULTS: There were 806 and 1346 stroke and IHD deaths, respectively. The major
      risk factors for stroke included age (hazard ratio [HR] = 1.15, 95% CI, 1.13
      1.17), smoking (HR = 1.71; 1.20-2.44), diabetes (HR = 1.75; 1.05-2.93), total
      cholesterol (HR per SD = 0.78; 0.69-0.89), and systolic BP (HR per SD = 1.22;
      1.08-1.38). In addition to these risk factors, IHD was also predicted by high
      density lipoprotein cholesterol, body mass index, C-reactive protein, and
      fibrinogen. This pattern of results was consistent among younger (<70 yrs) and
      older adults. CONCLUSION: In a large representative cohort of the general
      population we found a differential pattern of risk markers for stroke compared
      with IHD. This was not explained by differences in age at onset of disease.

PMID- 21889147
TI  - Proprotein convertases in human atherosclerotic plaques: the overexpression of
      FURIN and its substrate cytokines BAFF and APRIL.
AB  - BACKGROUND: Proprotein convertase subtilisin/kexin (PCSK) enzymes cleave
      proproteins into mature end products. Previously, MBTPS1 and PCSK9 have been
      shown to regulate cholesterol metabolism and LDL receptor recycling, whereas
      FURIN and PCSK5 have been suggested to inactivate lipases and regulate
      inflammation in atherosclerosis. Here, we systematically analyzed the expression
      of PCSKs and their targets in advanced atherosclerotic plaques. METHODS AND
      RESULTS: Microarray and quantitative real-time PCR experiments showed that FURIN
      (42.86 median fold, p = 2.1e-8), but no other PCSK, is universally overexpressed
      in the plaques of different vascular regions. The mRNA expression screen of PCSK
      target proteins in plaques identified many known factors, but it also identified
      the significant upregulation of the previously overlooked furin-processed B cell
      activating cytokines APRIL (TNFSF13, 2.52 median fold, p = 3.0e-5) and BAFF
      (TNFSF13B, 2.97 median fold, p = 7.6e-6). The dysregulation of FURIN did not
      associate with its htSNPs or the previously reported regulatory SNP (-229,
      rs4932178) in the promoter. Immunohistochemistry experiments showed the
      upregulation of FURIN in the plaque lymphocytes and macrophages where it was co
      expressed with BAFF/TNFSF13B and APRIL/TNFSF13. CONCLUSIONS: Our data
      unequivocally show that FURIN is the primary PCSK that is dysregulated in the
      immune cells of advanced human atherosclerotic plaques, which implies a role for
      this enzyme in plaque pathology. Therefore, drugs that inhibit FURIN in arteries
      may modulate the course of this disease.

PMID- 21889148
TI  - Determination of dynamic ankle ligament strains from a computational model driven
      by motion analysis based kinematic data.
AB  - External rotation of the foot has been implicated in high ankle sprains. Recent
      studies by this laboratory, and others, have suggested that torsional traction
      characteristics of the shoe-surface interface may play a role in ankle injury.
      While ankle injuries most often involve damage to ligaments due to excessive
      strains, the studies conducted by this laboratory and others have largely used
      surrogate models of the lower extremity to determine shoe-surface interface
      characteristics based on torque measures alone. The objective of this study was
      to develop a methodology that would integrate a motion analysis-based kinematic
      foot model with a computational model of the ankle to determine dynamic ankle
      ligament strains during external foot rotation. Six subjects performed single
      legged, internal rotation of the body with a planted foot while a marker-based
      motion analysis was conducted to track the hindfoot motion relative to the tibia.
      These kinematic data were used to drive an established computational ankle model.
      Ankle ligament strains, as a function of time, were determined. The anterior
      tibiofibular ligament (ATiFL) experienced the highest strain at 9.2+/-1.1%,
      followed by the anterior deltoid ligament (ADL) at 7.8+/-0.7%, averaged over the
      six subjects. The peak ATiFL strain occurred prior to peak strain in the ADL in
      all subjects. This novel methodology may provide new insights into mechanisms of
      high ankle sprains and offer a basis for future evaluations of shoe-surface
      interface characteristics using human subjects rather than mechanical surrogate
      devices.

PMID- 21889149
TI  - Direct in vivo strain measurements in human bone-a systematic literature review.
AB  - Bone strain is the governing stimuli for the remodeling process necessary in the
      maintenance of bone's structure and mechanical strength. Strain gages are the
      gold standard and workhorses of human bone experimental strain analysis in vivo.
      The objective of this systematic literature review is to provide an overview for
      direct in vivo human bone strain measurement studies and place the strain results
      within context of current theories of bone remodeling (i.e. mechanostat theory).
      We employed a standardized search strategy without imposing any time restriction
      to find English language studies indexed in PubMed and Web of Science databases
      that measured human bone strain in vivo. Twenty-four studies met our final
      inclusion criteria. Seven human bones were subjected to strain measurements in
      vivo including medial tibia, second metatarsal, calcaneus, proximal femur, distal
      radius, lamina of vertebra and dental alveolar. Peak strain magnitude recorded
      was 9096 MUepsilon on the medial tibia during basketball rebounding and the peak
      strain rate magnitude was -85,500 MUepsilon/s recorded at the distal radius
      during forward fall from standing, landing on extended hands. The tibia was the
      most exposed site for in vivo strain measurements due to accessibility and being
      a common pathologic site of stress fracture in the lower extremity. This
      systematic review revealed that most of the strains measured in vivo in different
      bones were generally within the physiological loading zone defined by the
      mechanostat theory, which implies stimulation of functional adaptation necessary
      to maintain bone mechanical integrity.

PMID- 21889150
TI  - A comparison of Coulomb and pseudo-Coulomb friction implementations: Application
      to the table contact phase of gymnastics vaulting.
AB  - In the table contact phase of gymnastics vaulting both dynamic and static
      friction act. The purpose of this study was to develop a method of simulating
      Coulomb friction that incorporated both dynamic and static phases and to compare
      the results with those obtained using a pseudo-Coulomb implementation of friction
      when applied to the table contact phase of gymnastics vaulting. Kinematic data
      were obtained from an elite level gymnast performing handspring straight
      somersault vaults using a Vicon optoelectronic motion capture system. An angle
      driven computer model of vaulting that simulated the interaction between a seven
      segment gymnast and a single segment vaulting table during the table contact
      phase of the vault was developed. Both dynamic and static friction were
      incorporated within the model by switching between two implementations of the
      tangential frictional force. Two vaulting trials were used to determine the model
      parameters using a genetic algorithm to match simulations to recorded
      performances. A third independent trial was used to evaluate the model and close
      agreement was found between the simulation and the recorded performance with an
      overall difference of 13.5%. The two-state simulation model was found to be
      capable of replicating performance at take-off and also of replicating key
      contact phase features such as the normal and tangential motion of the hands. The
      results of the two-state model were compared to those using a pseudo-Coulomb
      friction implementation within the simulation model. The two-state model achieved
      similar overall results to those of the pseudo-Coulomb model but obtained
      solutions more rapidly.

PMID- 21889151
TI  - Synthesis of caffeic acid molecularly imprinted polymer microspheres and high
      performance liquid chromatography evaluation of their sorption properties.
AB  - In the current work, a molecularly imprinted polymer (MIP) has been synthesised
      and used to enable the extraction of a naturally-occurring antioxidant from
      complex media. More specifically, we describe the first example of a caffeic acid
      (CA) MIP which has been synthesised in the form of well-defined polymer
      microspheres, and its use for the extraction of CA from fruit juice sample. The
      CA MIP was synthesised by precipitation polymerisation using 4-vinylpyridine as
      functional monomer, divinylbenzene-80 as crosslinker and acetonitrile:toluene
      (75/25, v/v) as porogen. The particle sizing and morphological characterisation
      of the polymers was carried out by means of scanning electron microscopy (narrow
      particle size distribution; ~5 and 1.5 MUm particle diameters for the MIP and NIP
      [non-imprinted polymer], respectively) and nitrogen sorption porosimetry
      (specific surface areas of 340 and 350 m(2)g(-1), and specific pore volumes of
      0.17 and 0.19 cm(3)g(-1) for the MIP and NIP, respectively). The polymers were
      evaluated further by batch rebinding experiments, and from the derived isotherms
      their binding capacity and binding strength were determined (number of binding
      sites (N(K))=0.6 and 0.3 mmol g(-1) for the MIP and NIP, respectively, and
      apparent average adsorption constant (K(N))=10.0 and 1.6L mmol(-1) for the MIP
      and NIP, respectively). To evaluate the molecular recognition character of the
      MIP it was packed into a stainless steel column (50 mm * 4.6 mm i.d.) and
      evaluated as an HPLC-stationary phase. The mobile phase composition, flow rate,
      and the elution profile were then optimised in order to improve the peak shape
      without negatively affecting the imprinting factor (IF). Very interesting,
      promising properties were revealed. The imprinting factor (IF) under the
      optimised conditions was 11.9. Finally, when the imprinted LC column was used for
      the selective recognition of CA over eight related compounds, very good
      selectivity was obtained. This outcome enabled the direct extraction of CA in
      commercial apple juice samples with recoveries in excess of 81% and, rather
      significantly, without any need for a clean-up step prior to the extraction.

PMID- 21889152
TI  - Drop shape visualization and contact angle measurement on curved surfaces.
AB  - The shape and contact angles of drops on curved surfaces is experimentally
      investigated. Image processing, spline fitting and numerical integration are used
      to extract the drop contour in a number of cross-sections. The three-dimensional
      surfaces which describe the surface-air and drop-air interfaces can be visualized
      and a simple procedure to determine the equilibrium contact angle starting from
      measurements on curved surfaces is proposed. Contact angles on flat surfaces
      serve as a reference term and a procedure to measure them is proposed. Such
      procedure is not as accurate as the axisymmetric drop shape analysis algorithms,
      but it has the advantage of requiring only a side view of the drop-surface couple
      and no further information. It can therefore be used also for fluids with unknown
      surface tension and there is no need to measure the drop volume. Examples of
      application of the proposed techniques for distilled water drops on gemstones
      confirm that they can be useful for drop shape analysis and contact angle
      measurement on three-dimensional sculptured surfaces.

PMID- 21889153
TI  - Synthesis and characterization of dendritic and porous Ag-Pd alloy
      nanostructures.
AB  - Dendritic and porous Ag-Pd alloy nanostructures were successfully fabricated on
      the surface of silicon substrate using the co-reduction method and galvanic
      replacement reaction, respectively. The molar compositions of Ag and Pd in the
      alloy could be modulated by controlling the molar ratios of metal precursors and
      reaction time. The Ag-Pd alloy nanostructures were characterized by transmission
      electron microscopy (TEM), high-resolution transmission electron microscopy
      (HRTEM), field emission scanning electron microscopy (FESEM), energy-dispersive X
      ray (EDX), and X-ray diffraction (XRD). The morphology and phase of Au-Pd alloy
      nanostructures were discussed as a function of molar ratios of metal precursors
      and reaction time. In addition, the morphology and composition-dependent surface
      enhanced Raman scattering (SERS) of the as-synthesized Ag-Pd alloy nanostructures
      were investigated. The SERS enhancement factor was estimated and SERS mapping was
      performed to prove the homogeneity of these substrates. The results indicate that
      as-synthesized dendritic and porous Ag-Pd alloy nanostructures are good
      candidates for SERS spectroscopy.

PMID- 21889154
TI  - Introduction of a planar defect in a molecularly imprinted photonic crystal
      sensor for the detection of bisphenol A.
AB  - This paper reports the preparation of a molecularly imprinted inverse opal
      hydrogel containing a 2D defect layer, by combining the Langmuir-Blodgett
      technique and the photonic crystal template method. By coupling the exceptional
      characteristics of molecularly imprinted polymers, sensitive to the presence of a
      target molecule, and those of photonic crystals in a single device, we could
      obtain a defect-embedded imprinted photonic polymer consisting in a three
      dimensional, highly-ordered and interconnected macroporous array, where
      nanocavities complementary to analytes in shape and binding sites are
      distributed. As a proof of concept, we prepared a three-dimensional macroporous
      array of poly(methacrylic acid) (PMAA) containing molecular imprints of bisphenol
      A (BPA) and a planar defect layer consisting in macropores of different size. The
      optical properties of the resulting inverse opal were investigated using
      reflection spectroscopy. The defect layer was shown to enhance the sensitivity of
      the photonic crystal material, opening new possibilities towards the development
      smart optical sensing devices.

PMID- 21889155
TI  - Wettability determination by contact angle measurements: hvbB coal-water system
      with injection of synthetic flue gas and CO2.
AB  - Geological sequestration of pure carbon dioxide (CO(2)) in coal is one of the
      methods to sequester CO(2). In addition, injection of CO(2) or flue gas into coal
      enhances coal bed methane production (ECBM). The success of this combined process
      depends strongly on the wetting behavior of the coal, which is function of coal
      rank, ash content, heterogeneity of the coal surface, pressure, temperature and
      composition of the gas. The wetting behavior can be evaluated from the contact
      angle of a gas bubble, CO(2) or flue gas, on a coal surface. In this study,
      contact angles of a synthetic flue gas, i.e. a 80/20 (mol%) N(2)/CO(2) mixture,
      and pure CO(2) on a Warndt Luisenthal (WL) coal have been determined using a
      modified pendant drop cell in a pressure range from atmospheric to 16 MPa and a
      constant temperature of 318 K. It was found that the contact angles of flue gas
      on WL coal were generally smaller than those of CO(2). The contact angle of CO(2)
      changes from water-wet to gas-wet by increasing pressure above 8.5 MPa while the
      one for the flue gas changes from water-wet to intermediate-wet by increasing
      pressure above 10 MPa.

PMID- 21889156
TI  - Effect of polymer molecular weight on the fiber morphology of electrospun mats.
AB  - In this work, different fractions of solvent-induced polymer degraded solution
      were mixed with freshly prepared solution of same polymer, and its effect on
      fiber morphology of electrospun mats was investigated. Nylon-6 solution in formic
      acid was allowed to degrade for 3 weeks and different fractions of it were mixed
      with freshly prepared nylon-6 solution to get the electrospun mats. FE-SEM images
      of the mats indicated that the a large amount of sub-nanofibers (<50 nm in
      diameter) in the form of spider-net like structures were achieved by tailoring
      the amount of solvent degraded polymer solution in the freshly prepared nylon-6
      solution. Large quantity of these ultrafine sub-nanofibers present in electrospun
      nylon-6 mats could increase its hydrophilicity and mechanical strength. The
      decreased average pore diameter and increased BET surface area of the mat, caused
      by spider-net like structure, can make it as a potential candidate for air/water
      filtration.

PMID- 21889157
TI  - High density silver nanoparticle monolayers produced by colloid self-assembly on
      polyelectrolyte supporting layers.
AB  - A stable silver nanoparticle suspension was synthesized via the reduction of
      silver nitrate using sodium borohydride and sodium citrate. The particle's shape
      and size distribution were measured by various methods. The electrophoretic
      mobility measurements revealed that the zeta potential of particles was highly
      negative, increasing slightly with the ionic strength, from -52 mV for I=10(-5) M
      to -35 mV for I=3*10(-2) M (for pH=5.5). The zeta potential of mica modified by
      the adsorption of cationic polyelectrolytes: PEI and PAH was also determined
      using the streaming potential measurements. The modified mica sheets were used as
      substrates for particle monolayers formed via colloid self assembly. The kinetics
      of this process, proceeding under diffusion-controlled transport conditions, was
      quantitatively evaluated by a direct enumeration of particles using the AFM and
      SEM techniques. Both the kinetics of particle deposition and the maximum surface
      concentration were determined. From the slope of the initial deposition rates,
      the equivalent diameter of particles was determined to be 16 nm, in agreement
      with previous measurements. Based on this finding, an efficient method of
      determining particle size in suspension was proposed. It was also demonstrated
      that for higher ionic strengths, the maximum coverage of particle monolayers on
      PAH modified mica exceeded 0.39. The kinetic data were quantitatively interpreted
      in terms of the random sequential adsorption (RSA) model using the effective hard
      particle concept.

PMID- 21889158
TI  - Superhydrophobic silicon surfaces with micro-nano hierarchical structures via
      deep reactive ion etching and galvanic etching.
AB  - An effective fabrication method combining deep reactive ion etching and galvanic
      etching for silicon micro-nano hierarchical structures is presented in this
      paper. The method can partially control the morphology of the nanostructures and
      enables us to investigate the effects of geometry changes on the properties of
      the surfaces. The forming mechanism of silicon nanostructures based on silver
      nanoparticle galvanic etching was illustrated and the effects of process
      parameters on the surface morphology were thoroughly discussed. It is found that
      process parameters have more impact on the height of silicon nanostructure than
      its diameter. Contact angle measurement and tilting/dropping test results show
      that as-prepared silicon surfaces with hierarchical structures were
      superhydrophobic. What's more, two-scale model composed of micropillar arrays and
      nanopillar arrays was proposed to study the wettability of the surface with
      hierarchical structures. Wettability analysis results indicate that the
      superhydrophobic surface may demonstrate a hybrid state at which water sits on
      nanoscale pillars and immerses into microscale grooves partially.

PMID- 21889159
TI  - Refolding of bovine serum albumin via artificial chaperone protocol using gemini
      surfactants.
AB  - Surfactants prevent the irreversible aggregation of partially refolded proteins,
      and they are also known to assist in protein refolding. A novel approach to
      protein refolding that utilizes a pair of low molecular weight folding
      assistants, a detergent and cyclodextrin, was proposed by Rozema and Gellman (D.
      Rozema, S.H. Gellman, J. Am. Chem. Soc. 117 (1995) 2373). We report the refolding
      of bovine serum albumin (BSA) assisted by these artificial chaperones, utilizing
      gemini surfactants for the first time. A combination of cationic gemini
      surfactants, bis(cetyldimethylammonium)pentane dibromide
      (C(16)H(33)(CH(3))(2)N(+)-(CH(2))(5)-N(+)(CH(3))(2)C(16)H(33).2Br(-) designated
      as G5 and bis(cetyldimethylammonium)hexane dibromide (C(16)H(33)(CH(3))(2)N(+)
      (CH(2))(6)-N(+)(CH(3))(2)C(16)H(33).2Br(-) designated as G6 and cyclodextrins,
      was used to refold guanidinium chloride (GdCl) denatured BSA in the artificial
      chaperone assisted two step method. The single chain cationic surfactant
      cetyltrimethylammonium bromide (CTAB) was used for comparative studies. The
      studies were carried out in an aqueous medium at pH 7.0 using circular dichroism,
      dynamic light scattering and ANS binding studies. The denatured BSA was found to
      get refolded by very small concentrations of gemini surfactant at which the
      single chain counterpart was found to be ineffective. Different from the single
      chain surfactant, the gemini surfactants exhibit much stronger electrostatic and
      hydrophobic interactions with the protein and are thus effective at much lower
      concentrations. Based on the present study it is expected that gemini surfactants
      may prove useful in the protein refolding operations and may thus be effectively
      employed to circumvent the problem of misfolding and aggregation.

PMID- 21889160
TI  - Considerations when determining low interfacial tensions.
AB  - Surfactants are often used to create low or "ultralow" oil-water interfacial
      tensions (IFTs). These molecules, in some cases, may also lead to the inadvertent
      formation of microemulsion phases which can obscure IFT measurements. Here, we
      present a case study of such an issue. We also introduce a little-known
      micropipette technique which has many advantages over the more common spinning
      drop method for determining low/ultralow IFTs.

PMID- 21889161
TI  - Preparation of bi-functional silica particles for antibacterial and self cleaning
      surfaces.
AB  - Synthesis of bi-functional silica particles by a simple wet chemical method is
      described where the mixture of ultra fine nanoparticles (1-3 nm) of titania and
      silver were attached on the silica particle surface in a controlled way to form a
      core-shell structure. The silica surface showed efficient bi-functional activity
      of photo-catalytically self cleaning and antibacterial activity due to
      nanotitania and nanosilver mutually benefiting each other's function. The optimum
      silver concentration was found where extremely small silver nanoparticles are
      formed and the total composite particle remains white in color. This is an
      important property in view of certain applications such as antibacterial textiles
      where the original fabric color has to be retained even after applying the
      nanosilver on it. The particles were characterized at each step of the synthesis
      by X-ray photoelectron spectroscopy, UV-visible spectroscopy, X-ray diffraction,
      scanning electron microscopy, transmission electron microscopy and electron
      energy loss spectroscopy. Bi-functional silica particles showed accelerated
      photocatalytic degradation of methylene blue as well as enhanced antibacterial
      property when tested as such particles and textiles coated with these bi
      functional silica particles even at lower silver concentration.

PMID- 21889162
TI  - Bacteria attachment to surfaces--AFM force spectroscopy and physicochemical
      analyses.
AB  - Understanding bacterial adhesion to surfaces requires knowledge of the forces
      that govern bacterial-surface interactions. Biofilm formation on stainless steel
      316 (SS316) by three bacterial species was investigated by examining surface
      force interaction between the cells and metal surface using atomic force
      microscopy (AFM). Bacterial-metal adhesion force was quantified at different
      surface delay time from 0 to 60s using AFM tip coated with three different
      bacterial species: Gram-negative Massilia timonae and Pseudomonas aeruginosa, and
      Gram-positive Bacillus subtilis. The results revealed that bacterial adhesion
      forces on SS316 surface by Gram-negative bacteria is higher (8.53+/-1.40 nN and
      7.88+/-0.94 nN) when compared to Gram-positive bacteria (1.44+/-0.21 nN).
      Physicochemical analysis on bacterial surface properties also revealed that M.
      timonae and P. aeruginosa showed higher hydrophobicity and surface charges than
      B. subtilis along with the capability of producing extracellular polymeric
      substances (EPS). The higher hydrophobicity, surface charges, and greater
      propensity to form EPS by M. timonae and P. aeruginosa led to high adhesive force
      on the metal surface.

PMID- 21889163
TI  - Improving the heat transfer efficiency of synthetic oil with silica
      nanoparticles.
AB  - The heat transfer properties of synthetic oil (Therminol 66) used for high
      temperature applications was improved by introducing 15 nm silicon dioxide
      nanoparticles. Stable suspensions of inorganic nanoparticles in the non-polar
      fluid were prepared using a cationic surfactant (benzalkonium chloride). The
      effects of nanoparticle and surfactant concentrations on thermo-physical
      properties (viscosity, thermal conductivity and total heat absorption) of these
      nanofluids were investigated in a wide temperature range. The surfactant-to
      nanoparticle (SN) ratio was optimized for higher thermal conductivity and lower
      viscosity, which are both critical for the efficiency of heat transfer. The
      rheological behavior of SiO(2)/TH66 nanofluids was correlated to average
      agglomerate sizes, which were shown to vary with SN ratio and temperature. The
      conditions of ultrasonic treatment were studied and the temporary decrease of
      agglomerate size from an equilibrium size (characteristic to SN ratio) was
      demonstrated. The heat transfer efficiencies were estimated for the formulated
      nanofluids for both turbulent and laminar flow regimes and were compared to the
      performance of the base fluid.

PMID- 21889164
TI  - Investigation of pH-responsive properties of polymeric micelles with a core
      forming block having pendant cyclic ketal groups.
AB  - In this study, three kinds of amphiphilic block copolymers, termed MPEG-block
      PDMMA, MPEG-block-PCPMA, and MPEG-block-PMPMA, which were composed of one
      hydrophilic monomethoxy poly(ethylene glycol) (MPEG) block and one hydrophobic
      polyacrylate block bearing pendant six-member cyclic ketal groups, were
      synthesized by atom transfer radical polymerization (ATRP). These polymers can
      disperse in aqueous media to self-assemble into micellar aggregates with a
      spherical core-shell structure with mean diameter below 300 nm. The stimuli
      responsiveness of polymeric micelles from MPEG-block-PDMMA was detected by
      fluorescence-probe technique at pH 3.5 and 37  degrees C. The effect of chemical
      architecture and composition of the polymers on the pH-responsive properties of
      polymeric micelles was also studied. A combination of pH and temperature to
      trigger release behavior of these polymeric micelles was discussed by comparing
      the encapsulated molecule release ability under various pH and temperature
      conditions and analyzing chemical structural changes of the polymer before and
      after the triggering.

PMID- 21889165
TI  - A floating prolate spheroid.
AB  - The equilibrium position of a spherical or prolate spheroidal particle resembling
      a needle floating at the interface between two immiscible fluids is discussed. A
      three-dimensional meniscus attached to an a priori unknown contact line at a
      specified contact angle is established around the particle, imparting to the
      particle a capillary force due to surface tension that is balanced by the
      buoyancy force and the particle weight. An accurate numerical solution for a
      floating sphere is obtained by solving a boundary-value problem, and the results
      are compared favorably with an approximate solution where the effect of the
      particle surface curvature is ignored and the elevation of the contact line is
      computed using an analytical solution for the meniscus attached to an inclined
      flat plate. The approximate formulation is applied locally around the nearly
      planar elliptical contact line of a prolate spheroid to derive a nonlinear
      algebraic equation governing the position of the particle center and the mean
      elevation of the contact line. The effect of the fluid and particle densities,
      contact angle, and capillary length is discussed, and the shape of the contact
      line is reconstructed and displayed from the local solution.

PMID- 21889166
TI  - Histopathological investigation of syringomyelia in the Cavalier King Charles
      spaniel.
AB  - Syringomyelia (SM) in Cavalier King Charles spaniels (CKCSs) is identified
      commonly on magnetic resonance images and is sometimes associated with clinical
      signs of pain and cervical hyperaesthesia. However, the mechanism by which SM
      develops in this breed has not been fully elucidated and the associated effects
      on spinal cord structure have not been reported previously. The aims of this
      study were to describe changes found in the spinal cord of CKCSs, to compare
      findings between symptomatic and asymptomatic dogs and to determine whether
      syrinx formation was associated with tissue destruction. Anomalies of the central
      canal were found in all specimens and many dogs had grossly visible fluid-filled
      cavities within the spinal cord. Prominent microscopical findings were spongy
      degenerative changes associated with neuronal necrosis and Wallerian
      degeneration. The ependyma was discontinuous in many specimens, notably in
      symptomatic individuals, and there was evidence of angiogenesis and fibrous
      tissue proliferation around blood vessels adjacent to syrinx cavities. Compared
      with two different samples of the normal dog population, dogs with syrinxes had
      significantly less grey matter, although this decrease was associated with
      generalized loss of spinal cord area. Therefore, SM is associated with
      degenerative changes in the spinal cord and may develop through primary
      disruption of ependymal integrity followed by vascular hypertrophy and
      proliferation. Glial and fibrous proliferation appears to be associated with
      expression of clinical signs.

PMID- 21889167
TI  - Affective symptoms are associated with markers of inflammation and immune
      activation in bipolar disorders but not in schizophrenia.
AB  - OBJECTIVE: Elevated levels of inflammation are reported in bipolar disorders
      (BP), but how this relates to affective symptoms is unclear. We aimed to
      determine if immune markers that consistently have been reported elevated in BP
      were associated with depressive and manic symptoms, and if this was specific for
      BP. METHODS: From a catchment area, 112 BP patients were included together with
      153 schizophrenia (SCZ) patients and 239 healthy controls. Depression and mania
      were assessed and the patients were grouped into depressed, neutral, and elevated
      mood. We measured the immune markers tumor necrosis factor receptor 1 (sTNF-R1),
      interleukin 1 receptor antagonist (IL-1Ra), interleukin 6 (IL-6), high sensitive
      C-reactive protein (hsCRP), osteoprotegerin (OPG) and von Willebrand factor (vWf)
      which have been found increased in severe mental disorders. RESULTS: In BP all
      inflammatory markers were lowest in depressed state, with significant group
      differences after control for confounders with respect to TNF-R1 (p = 0.04), IL
      1Ra (p = 0.02), OPG (p = 0.004) and IL-6 (p = 0.005). STNF-R1 was positively
      correlated with the item elevated mood (p = 0.02) whereas sad mood was negatively
      correlated with OPG (p = 0.0003), IL-1Ra (p = 0.001) and IL-6 (p = 0.006).
      Compared to controls the neutral mood group had significantly higher levels of
      OPG (p = 0.0003) and IL-6 (p = 0.005), and the elevated mood group had higher
      levels of TNF-R1 (p = 0.000005) and vWf (p = 0.002). There were no significant
      associations between affective states orsymptoms in SCZ. CONCLUSIONS: The current
      associations between inflammatory markers and affective symptomatology in BP and
      not SCZ suggest that immune related mechanisms are associated with core
      psychopathology of BP.

PMID- 21889168
TI  - Complete recovery of acute monocular visual loss following endoscopic resection
      of anterior clinoid mucocele: case report and review of the literature.
AB  - Mucoceles are chronic non-neoplastic cystic lesions lined by mucus-secreting
      respiratory epithelium in the paranasal sinuses. Mucocele of the anterior clinoid
      process is a particularly rare entity most often presenting with rapidly
      progressive monocular blindness. The authors describe the case of a 32 year-old
      man who presented with acute painless visual loss in the left eye. Workup
      revealed an expansile lesion of the left anterior clinoid process with associated
      optic nerve compression. The patient underwent emergent endoscopic-assisted
      transnasal decompression of the optic nerve with full recovery of visual
      function. Early diagnosis and prompt surgical intervention optimizes the chances
      of functional regain of visual acuity.

PMID- 21889169
TI  - A study of the prevalence of restless legs syndrome in previously untreated
      Parkinson's disease patients: absence of co-morbid association.
AB  - OBJECTIVE: The co-morbidity between Parkinson's disease (PD) and restless legs
      syndrome (RLS) is currently controversial, mainly because in most of the studies
      so far conducted, the patients were already on therapy with dopamine(DA)ergic
      drugs. This study has been carried out to assess the prevalence of RLS in de novo
      PD patients previously unexposed to DAergic drugs. METHODS: One hundred nine
      cognitively unimpaired outpatients with PD (70M/39F), mean age 66.89 years+/-9.37
      SD were included in the study. The mean duration of PD was 15.81 months+/-11.24
      SD, and the median Hoehn and Yahr (H&Y) stage was 2 (range 1.5-3). All patients
      underwent interview to assess the occurrence of overall life-time and current
      "primary" form of RLS according to the criteria of the International RLS Study
      Group (IRLSSG). One hundred sixteen age and sex matched subjects (74M/42F, mean
      age 66.52.years+/-8.65 SD) free from a history of neurological diseases, were
      taken as controls and likewise interviewed. "Secondary" forms of RLS in both
      patients and controls were subsequently excluded. RESULTS: No significant
      difference was found (chi-square test) in the frequency of overall life-time and
      of current "primary" RLS between PD patients and controls (6 out of 109 versus 5
      out of 116 and 3 out of 109 versus 3 out of 116, respectively). CONCLUSIONS: This
      survey does not support the concept of a co-morbid association between the two
      conditions and confirm indirectly the findings of previous studies reporting the
      onset of RLS after diagnosis of PD has been made in the great majority of
      patients and so likely on ongoing DAergic treatment. Therefore, we speculate that
      RLS occurring in these patients could be related to DAergic therapy for PD.

PMID- 21889170
TI  - A review of sediment and nutrient concentration data from Australia for use in
      catchment water quality models.
AB  - Land use (and land management) change is seen as the primary factor responsible
      for changes in sediment and nutrient delivery to water bodies. Understanding how
      sediment and nutrient (or constituent) concentrations vary with land use is
      critical to understanding the current and future impact of land use change on
      aquatic ecosystems. Access to appropriate land-use based water quality data is
      also important for calculating reliable load estimates using water quality
      models. This study collated published and unpublished runoff, constituent
      concentration and load data for Australian catchments. Water quality data for
      total suspended sediments (TSS), total nitrogen (TN) and total phosphorus (TP)
      were collated from runoff events with a focus on catchment areas that have a
      single or majority of the contributing area under one land use. Where possible,
      information on the dissolved forms of nutrients were also collated. For each data
      point, information was included on the site location, land use type and
      condition, contributing catchment area, runoff, laboratory analyses, the number
      of samples collected over the hydrograph and the mean constituent concentration
      calculation method. A total of ~750 entries were recorded from 514 different
      geographical sites covering 13 different land uses. We found that the nutrient
      concentrations collected using "grab" sampling (without a well defined
      hydrograph) were lower than for sites with gauged auto-samplers although this
      data set was small and no statistical analysis could be undertaken. There was no
      statistically significant difference (p<0.05) between data collected at plot and
      catchment scales for the same land use. This is most likely due to differences in
      land condition over-shadowing the effects of spatial scale. There was, however, a
      significant difference in the concentration value for constituent samples
      collected from sites where >90% of the catchment was represented by a single land
      use, compared to sites with <90% of the upstream area represented by a single
      land use. This highlights the need for more single land use water quality data,
      preferably over a range of spatial scales. Overall, the land uses with the
      highest median TSS concentrations were mining (~50,000mg/l), horticulture
      (~3000mg/l), dryland cropping (~2000mg/l), cotton (~600mg/l) and grazing on
      native pastures (~300mg/l). The highest median TN concentrations are from
      horticulture (~32,000MUg/l), cotton (~6500MUg/l), bananas (~2700MUg/l), grazing
      on modified pastures (~2200MUg/l) and sugar (~1700MUg/l). For TP it is forestry
      (~5800MUg/l), horticulture (~1500MUg/l), bananas (~1400MUg/l), dryland cropping
      (~900mg/l) and grazing on modified pastures (~400MUg/l). For the dissolved
      nutrient fractions, the sugarcane land use had the highest concentrations of
      dissolved inorganic nitrogen (DIN), dissolved organic nitrogen (DON) and
      dissolved organic phosphorus (DOP). Urban land use had the highest concentrations
      of dissolved inorganic phosphorus (DIP). This study provides modellers and
      catchment managers with an increased understanding of the processes involved in
      estimating constituent concentrations, the data available for use in modelling
      projects, and the conditions under which they should be applied. Areas requiring
      more data are also discussed.

PMID- 21889171
TI  - Recommendations on methods for the detection and control of biological pollution
      in marine coastal waters.
AB  - Adverse effects of invasive alien species (IAS), or biological pollution, is an
      increasing problem in marine coastal waters, which remains high on the
      environmental management agenda. All maritime countries need to assess the size
      of this problem and consider effective mechanisms to prevent introductions, and
      if necessary and where possible to monitor, contain, control or eradicate the
      introduced impacting organisms. Despite this, and in contrast to more enclosed
      water bodies, the openness of marine systems indicates that once species are in
      an area then eradication is usually impossible. Most institutions in countries
      are aware of the problem and have sufficient governance in place for management.
      However, there is still a general lack of commitment and concerted action plans
      are needed to address this problem. This paper provides recommendations resulting
      from an international workshop based upon a large amount of experience relating
      to the assessment and control of biopollution.

PMID- 21889172
TI  - Habitat associations of floating debris and marine birds in the North East
      Pacific Ocean at coarse and meso spatial scales.
AB  - While many surface foraging seabirds ingest plastic, the spatial overlap of these
      far-ranging predators with debris aggregations at-sea is poorly understood. We
      surveyed concurrent distributions of marine birds and debris along a 4400 km
      cruise track within a debris accumulation area in the North East Pacific Ocean
      using line and strip transect methods. Analysis of debris and bird distributions
      revealed associations with oceanographic and weather variables at two spatial
      scales: daily surveys and hourly transects. Hourly bird abundance (densities; 0-9
      birds km(-2)) was higher in lower wind and shallower water. Hourly debris
      abundance (densities; 0-15,222 pieces km(-2)) was higher in lower wind, higher
      sea-level atmospheric pressure and deeper water. These results suggest that
      debris and seabird abundance and community structure are influenced by similar
      environmental processes, but in opposing ways, with only three far-ranging
      seabird species (Black-footed Albatross, Cook's Petrel and Red-tailed Tropicbird)
      overlapping with high debris concentrations over meso-scales.

PMID- 21889173
TI  - Rapid quantification of infectious enterovirus from surface water in Bohai Bay,
      China using an integrated cell culture-qPCR assay.
AB  - To rapidly quantify infectious enteroviruses polluting the coastal seawaters, a
      newly developed integrated cell culture and reverse transcription quantitative
      PCR (ICC-RT-qPCR) assay was used to identify the contamination by enteroviruses
      in winter seawater samples of Bohai Bay, Tianjin, China. The gene copies of
      enteroviral 5'UTRs correlated to the initial inoculum numbers across the
      concentration range of 0.05-500 PFU mL(-1) (correlation coefficient (R(2)) was
      0.9667). ICC-qPCR revealed that five of seven samples (70.4%) were positive for
      infectious enteroviruses. The concentration of enteroviruses was estimated at 0.2
      21 PFU L(-1). The result demonstrated that the contamination of enteroviruses in
      this coastal area may constitute a potential public health risk. This study
      established a practical assay for widespread monitoring studies of aquatic
      environments for viral contamination and provided meaningful data for human
      waterborne viral risk assessment.

PMID- 21889174
TI  - Calcareous impact on arbuscular mycorrhizal fungus development and on lipid
      peroxidation in monoxenic roots.
AB  - The present work underlined the negative effects of increasing CaCO(3)
      concentrations (5, 10 and 20 mM) both on the chicory root growth and the
      arbuscular mycorrhizal fungus (AMF) Glomus irregulare development in monoxenic
      system. CaCO(3) was found to reduce drastically the main stages of G. irregulare
      life cycle (spore germination, germinative hyphae elongation, root colonization,
      extraradical hyphae development and sporulation) but not to inhibit it
      completely. The root colonization drop was confirmed by the decrease in the
      arbuscular mycorrhizal fungal marker C16:1omega5 amounts in the mycorrhizal
      chicory roots grown in the presence of CaCO(3). Oxidative damage evaluated by
      lipid peroxidation increase measured by (i) malondialdehyde (MDA) production and
      (ii) the antioxidant enzyme peroxidase (POD) activities, was highlighted in
      chicory roots grown in the presence of CaCO(3). However, MDA formation was
      significantly higher in non-mycorrhizal roots as compared to mycorrhizal ones.
      This study pointed out the ability of arbuscular mycorrhizal symbiosis to enhance
      plant tolerance to high levels of CaCO(3) by preventing lipid peroxidation and so
      less cell membrane damage.

PMID- 21889175
TI  - Identification of lignans and related compounds in Anthriscus sylvestris by LC
      ESI-MS/MS and LC-SPE-NMR.
AB  - The aryltetralin lignan deoxypodophyllotoxin is much more widespread in the plant
      kingdom than podophyllotoxin. The latter serves as a starting compound for the
      production of cytostatic drugs like etoposide. A better insight into the
      occurrence of deoxypodophyllotoxin combined with detailed knowledge of its
      biosynthestic pathway(s) may help to develop alternative sources for
      podophyllotoxin. Using HPLC combined with electrospray tandem mass spectrometry
      and NMR spectroscopy techniques, we found nine lignans and five related
      structures in roots of Anthriscus sylvestris (L.) Hoffm. (Apiaceae), a common
      wild plant in temperate regions of the world. Podophyllotoxone,
      deoxypodophyllotoxin, yatein, anhydropodorhizol, 1-(3'-methoxy-4',5'
      methylenedioxyphenyl)1-xi-methoxy-2-propene, and 2-butenoic acid, 2-methyl-4
      [[(2Z)-2-methyl-1-oxo-2-buten-1-yl]oxy]-, (2E)-3-(7-methoxy-1,3-benzodioxol-5-yl)
      2-propen-1-yl ester, (2Z)- were the major compounds. alpha-Peltatin,
      podophyllotoxin, beta-peltatin, isopicropodophyllone, beta-peltatin-a
      methylether, (Z)-2-angeloyloxymethyl-2-butenoic acid, anthriscinol methylether,
      and anthriscrusin were present in lower concentrations. alpha-Peltatin, beta
      peltatin, isopicropodophyllone, podophyllotoxone, and beta-peltatin-a-methylether
      have not been previously reported to be present in A. sylvestris. Based on our
      findings we propose a hypothetical biosynthetic pathway of aryltetralin lignans
      in A. sylvestris.

PMID- 21889176
TI  - Angustilobine and andranginine type indole alkaloids and an uleine
      secovallesamine bisindole alkaloid from Alstonia angustiloba.
AB  - A total of 20 alkaloids were isolated from the leaf and stem-bark extracts of
      Alstonia angustiloba, of which two are hitherto unknown. One is an alkaloid of
      the angustilobine type (angustilobine C), while the other is a bisindole alkaloid
      angustiphylline, derived from the union of uleine and secovallesamine moieties.
      The structures of these alkaloids were established using NMR and MS analysis.
      Angustilobine C showed moderate cytotoxicity towards KB cells.

PMID- 21889177
TI  - Identification of GABA A receptor modulators in Kadsura longipedunculata and
      assignment of absolute configurations by quantum-chemical ECD calculations.
AB  - A petroleum ether extract of Kadsura longipedunculata enhanced the GABA-induced
      chloride current (I(GABA)) by 122.5+/-0.3% (n=2) when tested at 100 MUg/ml in
      Xenopuslaevis oocytes expressing GABA A receptors (alpha(1)beta(2)gamma(2S)
      subtype) in two-microelectrode voltage clamp measurements. Thirteen compounds
      were subsequently identified by HPLC-based activity profiling as responsible for
      GABA A receptor activity and purified in preparative scale. 6-Cinnamoyl-6,7
      dihydro-7-myrceneol and 5,6-dihydrocuparenic acid were thereby isolated for the
      first time. The determination of the absolute stereochemistry of these compounds
      was achieved by comparison of experimental and calculated ECD spectra. All but
      one of the 13 isolated compounds from K. longipedunculata potentiated I(GABA)
      through GABA A receptors composed of alpha(1)beta(2)gamma(2S) subunits in a
      concentration-dependent manner. Potencies ranged from 12.8+/-3.1 to 135.6+/-85.7
      MUM, and efficiencies ranged from 129.7+/-36.8% to 885.8+/-291.2%. The
      phytochemical profiles of petroleum ether extracts of Kadsura japonica fruits
      (114.1+/-2.6% potentiation of I(GABA) at 100 MUg/ml, n=2), and Schisandra
      chinensis fruits (inactive at 100 MUg/ml) were compared by HPLC-PDA-ESIMS with
      that of K. longipedunculata.

PMID- 21889178
TI  - [Thyrotoxic hypokaliemic periodic paralysis revealing Graves' disease in a male
      Caucasian].
AB  - OBJECTIVES: Hypokaliemic thyrotoxic periodic paralysis (TPP) is an uncommon
      complication of hyperthyroidism. Mostly described among Asian patients, it is
      rare in other ethnic groups, in particular in Caucasian people. CASE REPORT: We
      present the case of a Caucasian male admitted to our unit after several paretic
      episodes. Tachycardia, goiter and mild proptosis led to the diagnosis of Graves'
      disease. CONCLUSION: Rare in the Caucasian population, TPP involves dysfunction
      of the NA-K-ATPase pump. Beta-blockers should be associated with medical or
      surgical treatment of hyperthyroidism.

PMID- 21889179
TI  - [Optimization of the radiotherapy for the gliomas: hopes and research axis for
      the next future].
AB  - Glioma and particularly glioblastoma are tumours of very bad prognosis despite
      association of surgery and radiochemotherapy. This bad prognosis is mainly due to
      the local relapse after radiochemotherapy which occurs invariably despite
      constant technical progress in radiotherapy. This local recurrence is mainly due
      to the biologic intracellular and micro-environmental radioresistance of these
      tumours but also to a probable bad definition of the irradiated target. The two
      main axis of research aiming at optimizing the radiotherapy of these patients
      will be discussed: on one hand, the study of the biological pathways involved in
      the tumor radioresistance in order to highlight new targets of interest and to
      inhibit them by targeted drugs in combination with radiotherapy, and on the other
      hand, research in metabolic and functional imaging with the aim to define areas
      of most aggressive disease and even predictive zones of the site of relapse and
      thus of radioresistance, in order to integrate them in the radiotherapy treatment
      planning in prospective trials.

PMID- 21889180
TI  - [Posterior reversible encephalopathy syndrome in a patient with lupus:
      differential diagnosis to discuss].

PMID- 21889181
TI  - Changing trends in visceral leishmaniasis: 10 years' experience at a referral
      hospital in Nepal.
AB  - Visceral leishmaniasis (VL) is mainly confined to the southeast area in the Terai
      region of Nepal. This study aimed to assess time trends and geographical
      distribution of VL at a referral hospital over a 10-year period in Kathmandu,
      Nepal. A total of 1521 patients were admitted to the hospital during the study
      period (April 1999 to March 2009). Overall, 88% of cases were from endemic areas
      and 10% were from non-endemic areas. There was a significant decreasing trend in
      the number of VL cases in this hospital during the study period. However, VL is
      being increasingly diagnosed in patients from non-endemic areas of Nepal. Whether
      VL in non-endemic areas is imported or autochthonous remains to be elucidated.
      This study therefore reinforces the need for urgent VL and entomological
      surveillance in newly reported areas to allow effective VL control strategies to
      be developed for the future.

PMID- 21889183
TI  - Biological iron oxidation by Gallionella spp. in drinking water production under
      fully aerated conditions.
AB  - Iron oxidation under neutral conditions (pH 6.5-8) may be a homo- or
      heterogeneous chemically- or a biologically-mediated process. The chemical
      oxidation is supposed to outpace the biological process under slightly alkaline
      conditions (pH 7-8). The iron oxidation kinetics and growth of Gallionella spp. -
      obligatory chemolithotrophic iron oxidizers - were assessed in natural, organic
      carbon-containing water, in continuous lab-scale reactors and full-scale
      groundwater trickling filters in the Netherlands. From Gallionella cell numbers
      determined by qPCR, balances were made for all systems. The homogeneous chemical
      iron oxidation occurred in accordance with the literature, but was retarded by a
      low water temperature (13  degrees C). The contribution of the heterogeneous
      chemical oxidation was, despite the presence of freshly formed iron
      oxyhydroxides, much lower than in previous studies in ultrapure water. This could
      be caused by the adsorption of natural organic matter (NOM) on the iron oxide
      surfaces. In the oxygen-saturated natural water with a pH ranging from 6.5 to
      7.7, Gallionella spp. grew uninhibited and biological iron oxidation was an
      important, and probably the dominant, process. Gallionella growth was not even
      inhibited in a full-scale filter after plate aeration. From this we conclude that
      Gallionella spp. can grow under neutral pH and fully aerated conditions when the
      chemical iron oxidation is retarded by low water temperature and inhibition of
      the autocatalytic iron oxidation.

PMID- 21889182
TI  - Delineation of a core RNA element required for Kaposi's sarcoma-associated
      herpesvirus ORF57 binding and activity.
AB  - The Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein is an essential
      multifunctional regulator of gene expression. ORF57 interaction with RNA is
      necessary for ORF57-mediated posttranscriptional functions, but little is known
      about the RNA elements that drive ORF57-RNA specificity. Here, we investigate the
      cis-acting factors on the KSHV PAN RNA that dictate ORF57 binding and activity.
      We show that ORF57 binds directly to the 5' end of PAN RNA in KSHV-infected
      cells. Furthermore, we employ in vitro and cell-based assays to define a 30
      nucleotide (nt) core ORF57-responsive element (ORE) that is necessary and
      sufficient for ORF57 binding and activity. Mutational analysis of the core ORE
      further suggests that a 9-nt sequence is a specific binding site for ORF57. These
      studies provide insight into ORF57 specificity determinants and lay a foundation
      for future analyses of cellular and viral ORF57 targets.

PMID- 21889184
TI  - Embodied energy comparison of surface water and groundwater supply options.
AB  - The embodied energy associated with water provision comprises an important part
      of water management, and is important when considering sustainability. In this
      study, an input-output based hybrid analysis integrated with structural path
      analysis was used to develop an embodied energy model. The model was applied to a
      groundwater supply system (Kalamazoo, Michigan) and a surface water supply system
      (Tampa, Florida). The two systems evaluated have comparable total energy
      embodiments based on unit water production. However, the onsite energy use of the
      groundwater supply system is approximately 27% greater than the surface water
      supply system. This was primarily due to more extensive pumping requirements. On
      the other hand, the groundwater system uses approximately 31% less indirect
      energy than the surface water system, mainly because of fewer chemicals used for
      treatment. The results from this and other studies were also compiled to provide
      a relative comparison of embodied energy for major water supply options.

PMID- 21889185
TI  - Seawater quality and microbial communities at a desalination plant marine
      outfall. A field study at the Israeli Mediterranean coast.
AB  - Global desalination quadrupled in the last 15 years and the relative importance
      of seawater desalination by reverse osmosis (SWRO) increased as well. While the
      technological aspects of SWRO plants are extensively described, studies on the
      environmental impact of brine discharge are lacking, in particular in situ marine
      environmental studies. The Ashqelon SWRO plant (333,000 m(3) d(-1) freshwater)
      discharges brine and backwash of the pre-treatment filters (containing ferric
      hydroxide coagulant) at the seashore, next to the cooling waters of a power
      plant. At the time of this study brine and cooling waters were discharged
      continuously and the backwash discharge was pulsed, with a frequency dependent on
      water quality at the intake. The effects of the discharges on water quality and
      neritic microbial community were identified, quantified and attributed to the
      different discharges. The mixed brine-cooling waters discharge increased salinity
      and temperature at the outfall, were positively buoyant, and dispersed at the
      surface up to 1340 m south of the outfall. Nutrient concentrations were higher at
      the outfall while phytoplankton densities were lower. Chlorophyll-a and
      picophytoplankton cell numbers were negatively correlated with salinity, but more
      significantly with temperature probably as a result of thermal pollution. The
      discharge of the pulsed backwash increased turbidity, suspended particulate
      matter and particulate iron and decreased phytoplankton growth efficiency at the
      outfall, effects that declined with distance from the outfall. The discharges
      clearly reduced primary production but we could not attribute the effect to a
      specific component of the discharge. Bacterial production was also affected but
      differently in the three surveys. The combined and possible synergistic effects
      of SWRO desalination along the Israeli shoreline should be taken into account
      when the three existing plants and additional ones are expected to produce 2
      Mm(3) d(-1) freshwater by 2020.

PMID- 21889186
TI  - Biological and clinical significance of NAC1 expression in cervical carcinomas: a
      comparative study between squamous cell carcinomas and
      adenocarcinomas/adenosquamous carcinomas.
AB  - This study examined the biological and clinical significance of NAC1 (nucleus
      accumbens associated 1) expression in both cervical squamous cell carcinomas and
      adenocarcinomas/adenosquamous carcinomas. Using immunohistochemistry, the
      frequency of positive NAC1 expression in adenocarcinomas/adenosquamous carcinomas
      (31.0%; 18/58) was significantly higher than that in squamous cell carcinomas
      (16.2%; 12/74) (P = .043). NAC1 gene amplification was identified by fluorescence
      in situ hybridization in 5 (7.2%) of 69 squamous cell carcinomas. NAC1
      amplification was not identified in the adenocarcinomas (0%; 0/58). Positive NAC1
      expression was significantly correlated with shorter overall survival in squamous
      cell carcinomas (P < .0001). A multivariate analysis showed that positive NAC1
      expression in squamous cell carcinomas was an independent prognostic factor for
      overall survival after standard radiotherapy (P = .0003). In contrast to squamous
      cell carcinomas, positive NAC1 expression did not correlate with shorter overall
      survival in adenocarcinomas/adenosquamous carcinomas (P = .317). Profound growth
      inhibition, increased apoptosis, decreased cell proliferation, and decreased cell
      migration and invasion were observed in silencing RNA-treated cancer cells with
      NAC1 overexpression compared with cancer cells without NAC1 expression. NAC1
      overexpression stimulated proliferation, migration, and invasion in the cervical
      cancer cell lines TCS and Hela P3, which normally lack NAC1 expression. These
      findings indicate that NAC1 overexpression is critical to the growth and survival
      of cervical carcinomas irrespective of histologic type. Furthermore, they suggest
      that NAC1 silencing RNA-induced phenotypes depend on the expression status of the
      targeted cell line. Therefore, cervical carcinoma patients with NAC1 expression
      may benefit from a targeted therapy irrespective of histologic type.

PMID- 21889187
TI  - Characteristic tubulointerstitial nephritis in IgG4-related disease.
AB  - Nephropathy associated with IgG4-related disease is characterized by
      tubulointerstitial nephritis. To better identify its pathology, the present study
      analyzed clinicopathologic features of IgG4-related tubulointerstitial nephritis
      cases from across Japan. Sixteen cases were identified as IgG4-related
      nephropathy using the criterion of high serum IgG4 levels (>135 mg/dL) with
      abnormal kidney computed tomography or elevated serum creatinine levels. Male
      predominance (75%) and advanced age (average, 62.0 years) were noted. Eight cases
      displayed no autoimmune pancreatitis. Renal computed tomography abnormalities
      were found in 12 of 13 cases examined. Renal dysfunction was found in 15 of 16
      cases at biopsy. Distinctive features of tubulointerstitial lesions included (1)
      well-demarcated borders between involved and uninvolved areas; (2) involvement of
      the cortex and medulla, often extending beyond the renal capsule and with
      occasional extension to retroperitoneal fibrosis; (3) interstitial inflammatory
      cells comprising predominantly plasma cells and lymphocytes, with a high
      prevalence of IgG4-positive cells often admixed with fibrosis; (4) peculiar
      features of interstitial fibrosis resembling a "bird's-eye" pattern comprising
      fibrosis among inter-plasma cell spaces; and (5) deposits visible by light and
      immunofluorescent microscopy in the tubular basement membrane, Bowman capsule,
      and interstitium that are restricted to the involved portion, sparing normal
      parts. Ultrastructural analysis revealed the presence of myofibroblasts with
      intracellular/pericellular collagen accompanied by plasma cell accumulation from
      an early stage. Histology could not discriminate between IgG4-related
      tubulointerstitial nephritis with and without autoimmune pancreatitis. In
      conclusion, the distinctive histologic features of IgG4-related
      tubulointerstitial nephritis can facilitate the differential diagnosis of
      tubulointerstitial nephritis, even without autoimmune pancreatitis or an abnormal
      computed tomography suggesting a renal tumor.

PMID- 21889188
TI  - Extensive brain pathology in a patient with aceruloplasminemia with a prolonged
      duration of illness.
AB  - We report the sixth autopsy case of a patient with aceruloplasminemia. He was the
      younger brother of the first reported autopsy case of this disease. Among autopsy
      cases with aceruloplasminemia reported to date, he had the longest duration of
      neurologic disorders. The neuropathologic findings showed that the basal ganglia
      and dentate nuclei were most severely affected. The most striking finding in the
      present case was that marked iron deposition was evident in the cerebral cortex.
      Many enlarged or deformed astrocytes and globular structures, both of which were
      heavily iron loaded, were found in the cerebral cortex as well as in the basal
      ganglia. Pyramidal neurons in his cerebral cortex were fewer in number than
      observed in the previous reported cases. There was a negative correlation between
      the number of cortical pyramidal neurons and globular structures. The present
      case clearly indicates that the neuropathologic process in aceruloplasminemia
      extends beyond the basal ganglia to the cerebral cortex with time.

PMID- 21889189
TI  - Assessment of nickel and cobalt release from 200 unused hand-held work tools for
      sale in Denmark - Sources of occupational metal contact dermatitis?
AB  - INTRODUCTION: Nickel and cobalt allergy remain frequent in dermatitis patients.
      It is important to determine possible nickel and cobalt exposures at work as
      these may offer important information to regulators and physicians who perform
      patch testing. Clinical relevance of metal exposure is usually assessed by the
      treating physician via the medical history and by presentation of allergic
      contact dermatitis. OBJECTIVES: To screen unused non-powered hand-held work tools
      for nickel and cobalt release by using colorimetric spot tests. MATERIALS &
      METHODS: A random selection of 200 non-powered hand-held work tools for sale in 2
      retailers of home improvement and construction products were analyzed
      qualitatively for metal release using the colorimetric nickel and cobalt spot
      tests. RESULTS: Nickel release was identified from 5% of 200 work tools using the
      dimethylglyoxime (DMG) test. In 8 of 10, positive results were located to the
      metal ring that acts like a cuff and is located at the end of the grip. The
      positive DMG test results were not related to specific categories of work tools.
      The cobalt spot test gave no positive test reactions. CONCLUSIONS: It appears
      that the proportion of work tools that release nickel, in amounts that may result
      in allergic nickel dermatitis, has decreased markedly, when results were compared
      with a Swedish study performed more than a decade ago. No cobalt release was
      detected but it should be underscored that hard-metal tools were not examined.
      Other sources of cobalt may explain the relatively high levels of cobalt allergy
      in dermatitis patients.

PMID- 21889190
TI  - Side effects of rodent control on non-target species: Rodenticides increase
      parasite and pathogen burden in great bustards.
AB  - For many years anticoagulant rodenticides have been used in vole control
      campaigns, in spite of the proven risk of secondary poisoning of non-target
      predators and scavengers. In this paper we analyse for the first time great
      bustard exposure and intoxication by anticoagulant rodenticides in Spain, based
      on residues found in the livers of 71 bustard carcasses collected during 1991
      2010. Ten individuals contained chlorophacinone and one flocoumafen.
      Chlorophacinone level was significantly correlated with the pathogen and parasite
      burden of intoxicated birds. Moreover, through the last 12 years the annual
      number of great bustards that present chlorophacinone in liver collected in our
      study areas was correlated with vole peaks at a nearby area, suggesting that the
      ingestion of rodenticide was proportional to the amounts spread in the fields. We
      conclude that rodenticide consumption is a regular event among great bustards
      when baited cereal is spread on fields, and that this may cause chronic weakening
      of intoxicated individuals, possibly affecting their survival. Future rodent
      control actions should consider these negative side effects on non target
      granivorous steppe and farmland species, particularly when they are globally
      threatened.

PMID- 21889192
TI  - Urinary MMP-2 and MMP-9 predict the presence of ovarian cancer in women with
      normal CA125 levels.
AB  - OBJECTIVE: To determine whether urinary matrix metalloproteinases (MMPs) predict
      the presence of ovarian cancer in patients with CA125 levels below the normal
      threshold of 35U/mL, a critical group of patients for whom no ovarian cancer
      biomarker is currently available. To determine whether these noninvasive
      biomarkers provide clinically useful information in the general ovarian cancer
      patient population as well. METHODS: ELISA analyses and substrate gel
      electrophoresis detected the levels and activity of urinary MMP-2, MMP-9, MMP
      9/neutrophil gelatinase-associated lipocalin (NGAL) complex, and MMP-9 dimer in
      all ovarian cancer patients (n=97), those with CA125 <35U/mL (n=26) and controls
      (n=81). RESULTS: In patients with CA125 <35U/mL, receiver-operating
      characteristic (ROC) area under curve (AUC) analysis demonstrated that either
      urinary MMP-2 or MMP-9 or NGAL significantly discriminated between controls and
      ovarian cancer patients with normal CA125. Multivariate logistic regression
      revealed that the combination of urinary MMP-2 and MMP-9 provided the best
      diagnostic accuracy when multiplexed. When further multiplexed with age, the
      diagnostic accuracy of these biomarkers increased to a significant AUC of 0.820.
      These findings were consistent among the general ovarian cancer population
      studied as well, where the combination of urinary MMP-2 and MMP-9 multiplexed
      with age resulted in a highly significant AUC of 0.881. Pearson chi-square
      analysis revealed that higher urinary levels of either MMP-2 or MMP-9 were
      strongly associated with the increasing percentage of women with ovarian cancer
      independent of CA125 levels. CONCLUSION: This study demonstrates the potential
      utility of urinary MMP-2 and MMP-9 to differentiate between ovarian cancer
      patients with normal CA125 levels and controls and suggests that urinary MMP-2
      and MMP-9 may be a clinically useful aid in the diagnosis of advanced or
      recurrent ovarian cancer.

PMID- 21889193
TI  - FIGO staging for carcinosarcoma: can the revised staging system predict overall
      survival?
AB  - OBJECTIVES: The purpose of this study is to detect differences in overall
      survival between the 1988 FIGO staging and current staging of uterine
      carcinosarcomas to determine if revised 2009 staging accurately predicts actual
      patient survival. METHODS: From 1988 until 2010, patients with uterine
      carcinosarcoma were retrospectively identified from tumor registry records.
      Patients were grouped in both broad stages (1-4) and all FIGO substages in order
      to detect differences. Time-dependent receiver operating characteristic curves
      (ROC) were generated to predict death before the end of the second year post
      diagnosis for both the new and revised system. Kaplan Meier estimated median
      survival time was utilized to compare actual patient survival. RESULTS: Of 112
      patients with carcinosarcoma, 37 patients (33%) had FIGO Stage I disease, 15
      patients (13.4%) had Stage II disease, 36 patients (32%) were diagnosed as Stage
      III, and 24 patients (21.4%) had Stage IV disease. 106 of 112 (94.6%) patients
      underwent lymphadenectomy (pelvic +/- para-aortic). Four patients (3.6%) were
      downstaged when utilizing broad staging criteria: 2 patients were downstaged from
      Stage II to I, and 2 patients were downstaged from Stage III to Stage I and II
      respectively. When looking at substage, the area under the ROC was 0.67 for the
      former staging system, and 0.65 for the revised staging. Kaplan-Meier estimated
      median survival time post-diagnosis was 610 days (95% CI [478,930]). CONCLUSION:
      Based upon our reclassification of 112 patients with uterine carcinosarcoma, the
      revised FIGO staging system does not predict survival more accurately than former
      staging. Carcinosarcoma has an overall poor prognosis and better indicators of
      survival are needed.

PMID- 21889195
TI  - From storage to manipulation: How the neural correlates of verbal working memory
      reflect varying demands on inner speech.
AB  - The ability to store and manipulate online information may be enhanced by an
      inner speech mechanism that draws upon motor brain regions. Neural correlates of
      this mechanism were examined using event-related functional magnetic resonance
      imaging (fMRI). Sixteen participants completed two conditions of a verbal working
      memory task. In both conditions, participants viewed one or two target letters.
      In the "storage" condition, these targets were held in mind across a delay. Then
      a probe letter was presented, and participants indicated by button press whether
      the probe matched the targets. In the "manipulation" condition, participants
      identified new targets by thinking two alphabetical letters forward of each
      original target (e.g., f->h). Participants subsequently indicated whether the
      probe matched the newly derived targets. Brain activity during the storage and
      manipulation conditions was examined specifically during the delay phase in order
      to directly compare manipulation versus storage processes. Activations that were
      common to both conditions, yet disproportionately greater with manipulation, were
      observed in the left inferior frontal cortex, premotor cortex, and anterior
      insula, bilaterally in the parietal lobes and superior cerebellum, and in the
      right inferior cerebellum. This network shares substrates with overt speech and
      may represent an inner speech pathway that increases activity with greater
      working memory demands. Additionally, an inverse correlation was observed between
      manipulation-related brain activity (on correct trials) and test accuracy in the
      left premotor cortex, anterior insula, and bilateral superior cerebellum. This
      inverse relationship may represent intensification of inner speech as one
      struggles to maintain performance levels.

PMID- 21889196
TI  - Neural correlates of metonymy resolution.
AB  - Metonymies are exemplary models for complex semantic association processes at the
      sentence level. We investigated processing of metonymies using event-related
      functional magnetic resonance imaging (fMRI). During an 1.5Tesla fMRI scan, 14
      healthy subjects (12 female) read 124 short German sentences with either literal
      (like "Africa is arid"), metonymic ("Africa is hungry"), or nonsense ("Africa is
      woollen") content. Sentences were constructed so that they obey certain
      grammatical, semantic, and plausibility conditions and were matched for word
      frequency, semantic association, length and syntactic structure. We concentrated
      on metonymies that were not yet fossilised; we also examined a wide variety of
      metonymic readings. Reading metonymies relative to literal sentences revealed
      signal changes in a predominantly left-lateralised fronto-temporal network with
      maxima in the left and right inferior frontal as well as left middle temporal
      gyri. Left inferior frontal activation may reflect both inference processes and
      access to world knowledge during metonymy resolution.

PMID- 21889194
TI  - BET bromodomain inhibition as a therapeutic strategy to target c-Myc.
AB  - MYC contributes to the pathogenesis of a majority of human cancers, yet
      strategies to modulate the function of the c-Myc oncoprotein do not exist. Toward
      this objective, we have targeted MYC transcription by interfering with chromatin
      dependent signal transduction to RNA polymerase, specifically by inhibiting the
      acetyl-lysine recognition domains (bromodomains) of putative coactivator proteins
      implicated in transcriptional initiation and elongation. Using a selective small
      molecule bromodomain inhibitor, JQ1, we identify BET bromodomain proteins as
      regulatory factors for c-Myc. BET inhibition by JQ1 downregulates MYC
      transcription, followed by genome-wide downregulation of Myc-dependent target
      genes. In experimental models of multiple myeloma, a Myc-dependent hematologic
      malignancy, JQ1 produces a potent antiproliferative effect associated with cell
      cycle arrest and cellular senescence. Efficacy of JQ1 in three murine models of
      multiple myeloma establishes the therapeutic rationale for BET bromodomain
      inhibition in this disease and other malignancies characterized by pathologic
      activation of c-Myc.

PMID- 21889197
TI  - Effects of diet on early stage cortical perception and discrimination of
      syllables differing in voice-onset time: a longitudinal ERP study in 3 and 6
      month old infants.
AB  - The influence of diet on cortical processing of syllables was examined at 3 and 6
      months in 239 infants who were breastfed or fed milk or soy-based formula. Event
      related potentials to syllables differing in voice-onset-time were recorded from
      placements overlying brain areas specialized for language processing. P1
      component amplitude and latency measures indicated that at both ages infants in
      all groups could extract and discriminate categorical information from syllables.
      Between-syllable amplitude differences-present across groups-were generally
      greater for SF infants. Responses peaked earlier over left hemisphere speech
      perception than speech-production areas. Encoding was faster in BF than formula
      fed infants. The results show that in preverbal infants: (1) discrimination of
      phonetic information occurs in early stages of cortical processing; (2) areas
      overlying brain regions of speech perception are activated earlier than those
      involved in speech production; and (3) these processes are differentially
      modulated by infant diet and environmental factors.

PMID- 21889198
TI  - Expression and activity of glutathione S-transferases and catalase in the shrimp
      Litopenaeus vannamei inoculated with a toxic Microcystis aeruginosa strain.
AB  - Microcystin (MC) produced during cyanobacteria blooms is notably toxic to human
      and wildlife. Conjugation with reduced glutathione (GSH) by glutathione S
      transferase (GST) and the antioxidant enzymes defenses (e.g. catalase, CAT) are
      important biochemical defense mechanisms against MCs toxicity. We investigated
      the enzymatic activity of CAT and GST and the gene expression levels of CAT and
      eight GST isoforms in the hepatopancreas of the globally farmed shrimp
      Litopenaeus vannamei 48-h after injection with a sub-lethal dose of 100 MUg kg-1
      of a toxic Microcystis aeruginosa extract. MCs caused up-regulation for GSTOmega,
      MU and a MAPEG isoform, by 12-, 2.8- and 1.8-fold, respectively, and increases in
      the total GST enzyme activity and CAT enzyme activity. The study points to the
      importance of further characterization for the L. vannamei GST isoforms and
      GST/CAT post-translational regulation processes to better understand the key
      mechanisms involved in the shrimp's defense against MC exposure.

PMID- 21889199
TI  - Cryopreservation of tissue-engineered epithelial sheets in trehalose.
AB  - Tissue-engineered epidermal membranes are useful for clinical wound healing. To
      facilitate these products in the clinic, optimized storage methods need to be
      developed. We studied the efficiency of extracellular trehalose at various
      concentrations for cryopreserving human tissue-engineered epidermal membranes
      compared with that of dimethyl-sulfoxide (DMSO) used by most organ banks for
      cryopreserving skin grafts and artificial skin substitutes. Keratinocyte (KC)
      viability, proliferation and marker expression following cryopreservation in
      trehalose were examined with similar results to those using DMSO. Trehalose
      concentration (0.4m) was optimized according to the described cellular activities
      following cryopreservation. Artificial epidermal substitutes were then
      cryopreserved in trehalose at the optimized concentration. Cell viability, growth
      factor secretion and wound healing properties of cryopreserved artificial
      epidermal substitutes using nude mice were examined and compared with those of
      DMSO cryopreservation. Cryopreservation with trehalose enhanced human KC
      viability in suspension and artificial skin substitutes. In addition, trehalose
      cryopreservation provided fast recovery of EGF and TGF-beta1 secretion by KCs
      after thawing. When transplanted into nude mice, trehalose-cryopreserved
      artificial skin repaired skin defects in a similar manner to that of a non
      cryopreserved control. Moreover, trehalose-cryopreserved artificial skin resulted
      in engraftment and wound closure that was significantly enhanced compared with
      that of DMSO-cryopreserved epidermal membranes. The results indicate that the use
      of trehalose improves cryopreservation of tissue-engineered epithelial sheets.

PMID- 21889200
TI  - The comparative effects of mesoporous silica nanoparticles and colloidal silica
      on inflammation and apoptosis.
AB  - Mesoporous silica (MPS), synthesized via the supramolecular polymer templating
      method, is one of the most attractive nanomaterials for biomedical applications,
      such as drug delivery systems, labeling, and tissue engineering. The significant
      difference between MPS and general silica (colloidal silica) is the pore
      architectures, such as specific surface area and pore volume. The pore structures
      of nanomaterials have been considered to be one of the key conditions, causing
      nanotoxicity due to their different efficiency of cellular uptake and immune
      response. We first studied the influence of pore structural conditions of silica
      nanoparticles on both inflammation and apoptosis, in vitro and in vivo, by
      comparing MPS and colloidal silica, and defined underlying mechanisms of action.
      Both the MPS and colloidal silica nanoparticles are produced by almost similar
      synthetic conditions, except the use of polymer template for MPS. The specific
      surface area of colloidal silica and MPS was 40 and 1150 m(2) g(-1),
      respectively, while other conditions, including particle size (100 nm) and shape
      (spherical), were kept constant. In both MTT assay and FACS analysis, MPS
      nanoparticles showed significantly less cytotoxicity and apoptotic cell death
      than colloidal silica nanoparticles. MPS nanoparticles induced lower expression
      of pro-inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin
      (IL)-1beta, and IL-6, in macrophages. The reduced inflammatory response and
      apoptosis elicited by MPS nanoparticles were resulting from the reduction of
      mitogen-activated protein kinases, nuclear factor-kappaB, and caspase 3. In
      addition, using the local lymph node assay, a standalone in vivo method for
      hazard identification of contact hypersensitivity, we showed that colloidal
      silica nanoparticles act as an immunogenic sensitizer and induce contact
      hypersensitivity but not MPS nanoparticles. In conclusion, the pore architecture
      of silica nanoparticles greatly influences their biocompatibility and should be
      carefully designed. The MPS nanoparticles exhibit better biocompatibility than
      colloidal silica and promise excellent potential usage in the field of biomedical
      and biotechnological applications.

PMID- 21889201
TI  - Cationic amylose-encapsulated bovine hemoglobin as a nanosized oxygen carrier.
AB  - Nanosized hemoglobin-based oxygen carriers are one of the most promising blood
      substitutes. In the present study, a comprehensive strategy for the preparation
      of nanosized cationic amylose-encapsulated hemoglobins (NCAHbs) was developed.
      First, cationic amylase (CA) was synthesized from amylose and quaternary ammonium
      salt by an etherification reaction. The structure of CA was characterized using
      Fourier transform infrared spectrophotometry (FTIR) and proton nuclear magnetic
      resonance spectrophotometry ((1)H NMR). The degree of substitution and the zeta
      potential were also measured. Then, the NCAHbs were prepared by electrostatic
      adhesion, reverse micelles and cross-linking. The UV-visible spectrophotometer
      was used to measure the entrapment efficiency (EE%) and drug loading efficiency
      (DL%) of the NCAHbs. Transmission electron microscopy and Malvern Nano-zs 90
      analyzer were used to observe the size distribution and morphology of particles.
      Chemical structure was determined from the FTIR spectrum. A Hemox analyzer was
      used to measure the P(50) and Hill coefficients. A lethal hemorrhagic shock model
      in rats was used to evaluate the therapeutic effect of the NCAHbs. The results
      showed that the combined methods improved the size, stability, EE%, DL%, and
      oxygen-carrying capacity of the NCAHbs. The average diameter of the NCAHbs was
      92.53 +/- 3.64 nm, with a narrow polydispersity index of 0.027. The EE% was
      80.05% +/- 1.56% and DL% was 61.55% +/- 1.41%. The P(50) and Hill coefficient
      were equal to 28.96 +/- 1.33 mmHg and 2.55 +/- 0.22, respectively. The size of
      NCAHbs remained below 200 nm for six days in PBS solution. The NCAHbs could
      effectively prevent lung injury from progressing to lethal hemorrhagic shock
      because they acted as both a volume expander and an oxygen carrier.

PMID- 21889202
TI  - The sequestration of hydroxyapatite nanoparticles by human monocyte-macrophages
      in a compartment that allows free diffusion with the extracellular environment.
AB  - Calcium phosphate and hydroxyapatite nanoparticles are extensively researched for
      medical applications, including bone implant materials, DNA and SiRNA delivery
      vectors and slow release vaccines. Elucidating the mechanisms by which cells
      internalize nanoparticles is fundamental for their long-term exploitation. In
      this study, we demonstrate that hydrophilic hydroxyapatite nanoparticles are
      sequestered within a specialized compartment called SCC (surface-connected
      compartment). This membrane-bound compartment is an elaborate labyrinth-like
      structure directly connected to the extracellular space. This continuity is
      demonstrated by in vivo 2-photon microscopy of ionic calcium using both cell
      permeable and cell-impermeable dyes and by 3-D reconstructions from serial block
      face SEM of fixed cells. Previously, this compartment was thought to be initiated
      specifically by exposure of macrophages to hydrophobic nanoparticles. However, we
      show that the SCC can be triggered by a much wider range of nanoparticles.
      Furthermore, we demonstrate its formation in A549 human lung epithelial cells,
      which are considerably less phagocytic than macrophages. EDX shows that extensive
      amounts of hydroxyapatite nanoparticles can be sequestered in this manner. We
      propose that SCC formation may be a means to remove large amounts of foreign
      material from the extracellular space, followed by slow degradation, may be to
      avoid excessive damage to surrounding cells or tissues.

PMID- 21889203
TI  - The functional performance of microencapsulated human pancreatic islet-derived
      precursor cells.
AB  - We have examined long-term cultured, human islet-derived stem/precursor cells
      (hIPC). Whole human islets (HI) were obtained by multi-enzymatic digestion of
      cadaveric donor pancreases, plated on tissue flasks, and allowed to adhere and
      expand for several in vitro passages, in order to obtain hIPC. We detected
      specific stem cell markers (Oct-4, Sox-2, Nanog, ABCG2, Klf-4, CD117) in both
      intact HI and hIPC. Moreover, hIPC while retaining the expression of Glut-2, Pdx
      1, CK-19, and ICA-512, started re-expressing Ngn3, thereby indicating acquisition
      of a specific pancreatic islet beta cell-oriented phenotype identity. The
      intrinsic plasticity of hIPC was documented by their ability to differentiate
      into various germ layer-derived cell phenotypes (ie, osteocytic, adipocytic and
      neural), including endocrine cells associated with insulin secretory capacity. To
      render hIPC suitable for transplantation we have enveloped them within our highly
      purified, alginate-based microcapsules. Upon intraperitoneal graft in NOD/SCID
      mice we have observed that the microcapsules acted as three-dimensional niches
      favouring post-transplant hIPC differentiation and acquisition of beta cell-like
      functional competence.

PMID- 21889204
TI  - Assessment of nanomaterial cytotoxicity with SOLiD sequencing-based microRNA
      expression profiling.
AB  - The cytotoxicity of nanomaterials has become a major concern in the field of
      nanotechnology. The key challenge is the lack of reliable methods to examine the
      overall cellular effects of nanomaterials. Here, a new method is developed to
      assess the cytological effects of nanomaterial basing on miRNA expression
      profiling. The SOLiD sequencing is used to acquire the miRNAs expression
      profiling in NIH/3T3 cells after exposure to Fe(2)O(3) NPs, CdTe QDs and MW-CNTs,
      respectively. The systematic analysis of miRNAs expression profiling is
      established by taking account of all miRNAs into their regulatory networks. By
      affecting the output of targeted mRNAs, miRNAs widely regulated the KEGG pathways
      and GO biological processes in nanomaterial treated cells. Therefore, the miRNA
      expression profiling can well reflect the characteristic of nanomaterials, and
      the method not only provide more evidences to assess biocompatibility of
      nanomaterials and but also clues to discover new biological effects of
      nanomaterials.

PMID- 21889206
TI  - Platinum (IV)-coordinate polymers as intracellular reduction-responsive backbone
      type conjugates for cancer drug delivery.
AB  - Platinum (IV)-coordinate polymers were synthesized by condensation polymerization
      using diamminedichlorodihydroxyplatinum (DHP) or its dicarboxyl derivative
      diamminedichlorodisuccinatoplatinum (DSP) as comonomers. Cyclic voltammogram
      study showed that Pt (IV) in the polymers was much easier reduced to Pt (II),
      particularly at the acidic pH, than that in the monomer DSP. Thus, these polymers
      were intracellular reduction-responsive backbone-type polymer conjugates that
      could be degraded and release Pt (II). These conjugates not only had high and
      fixed platinum contents (27.7% for P(DSP-EDA) and 29.6% for P(DSP-PA),
      respectively), but also showed increased cytotoxicity compared with corresponding
      Pt (IV) monomer DSP toward various tumor cell lines. In vivo, the conjugate
      showed a longer blood circulation time and better tumor accumulation.

PMID- 21889205
TI  - The use of injectable sonication-induced silk hydrogel for VEGF(165) and BMP-2
      delivery for elevation of the maxillary sinus floor.
AB  - Sonication-induced silk hydrogels were previously prepared as an injectable bone
      replacement biomaterial, with a need to improve osteogenic features. Vascular
      endothelial growth factor (VEGF(165)) and bone morphogenic protein-2 (BMP-2) are
      key regulators of angiogenesis and osteogenesis, respectively, during bone
      regeneration. Therefore, the present study aimed at evaluating in situ forming
      silk hydrogels as a vehicle to encapsulate dual factors for rabbit maxillary
      sinus floor augmentation. Sonication-induced silk hydrogels were prepared in
      vitro and the slow release of VEGF(165) and BMP-2 from these silk gels was
      evaluated by ELISA. For in vivo studies for each time point (4 and 12 weeks), 24
      sinus floors elevation surgeries were made bilaterally in 12 rabbits for the
      following four treatment groups: silk gel (group Silk gel), silk gel/VEGF(165)
      (group VEGF), silk gel/BMP-2 (group BMP-2), silk gel/VEGF(165)/BMP-2 (group V +
      B) (n = 6 per group). Sequential florescent labeling and radiographic
      observations were used to record new bone formation and mineralization, along
      with histological and histomorphometric analysis. At week 4, VEGF(165) promoted
      more tissue infiltration into the gel and accelerated the degradation of the gel
      material. At this time point, the bone area in group V + B was significantly
      larger than those in the other three groups. At week 12, elevated sinus floor
      heights of groups BMP-2 and V + B were larger than those of the Silk gel and VEGF
      groups, and the V + B group had the largest new bone area among all groups. In
      addition, a larger blood vessel area formed in the remaining gel areas in groups
      VEGF and V + B. In conclusion, VEGF(165) and BMP-2 released from injectable and
      biodegradable silk gels promoted angiogenesis and new bone formation, with the
      two factors demonstrating an additive effect on bone regeneration. These results
      indicate that silk hydrogels can be used as an injectable vehicle to deliver
      multiple growth factors in a minimally invasive approach to regenerate irregular
      bony cavities.

PMID- 21889207
TI  - Defining fetal growth restriction in mice: A standardized and clinically relevant
      approach.
AB  - The increasing number of mouse models of fetal growth restriction (FGR) make it
      crucial to standardize the way FGR is defined. By constructing growth curves in
      the placental-specific Igf2 knockout mouse (P0) it was demonstrated that 93% of
      P0 fetuses fell below the 5th centile of wild-type weights at E18.5, up from 44%
      at E16.5. This analysis, coupled with anthropomorphic measurements showing
      evidence of head sparing in P0 fetuses, allows clinical comparisons of FGR in
      mice through the use of clinically relevant growth curves. We suggest this as a
      standardized approach to defining FGR in mouse, and other animal models.

PMID- 21889208
TI  - Placental inflammation and oxidative stress in the mouse model of assisted
      reproduction.
AB  - Higher rates of low birth weight and prematurity are observed in pregnancies
      generated with assisted reproduction technologies (ART). Both conditions have
      been associated with placental inflammation and oxidative stress. Since placental
      and fetal levels of progesterone, a major anti-inflammatory steroid, are
      decreased in murine ART, we investigated placental inflammation and oxidative
      stress in this model as potential mediators of negative birth outcomes. After
      generating mouse pregnancies by in vitro fertilization (IVF) and intracytoplasmic
      sperm injection (ICSI) we evaluated the antioxidant defense network and major
      inflammatory cytokines in maternal, placental and fetal tissues. Additionally,
      placentas were analyzed for total lipid levels, fibrosis, apoptosis, reactive
      oxygen species and integrity of intracellular nucleotides. Placentas from ART
      contained significantly less lipids, with greater levels of apoptosis and
      degraded nucleotides. Placentas from ICSI pregnancies had lower activities of
      superoxide dismutase (SOD), thioredoxin reductase (TrxR), xanthine oxidase (XO),
      catalase, glutathione-S-transferase (GST) glutathione peroxidase, and glutathione
      reductase (GR). Furthermore, GR, GST and SOD were also lower in fetal livers from
      ICSI pregnancies. Placentas from IVF pregnancies had decreased levels of SOD,
      TrxR and XO only. In placentas from both ICSI and IVF pregnancies IL-6 levels
      were significantly increased. These data suggest that ART is associated with
      placental inflammation (IL-6), oxidative stress and apoptosis but not fibrosis or
      remodeling. These effects are markedly greater with the ICSI technique. Since
      ICSI is ubiquitous, oxidative stress and placental inflammation associated with
      this method may be a critical factor in negative birth outcomes such as
      prematurity and low birth weight.

PMID- 21889209
TI  - Role of 657del5 NBN mutation and 7p12.2 (IKZF1), 9p21 (CDKN2A), 10q21.2 (ARID5B)
      and 14q11.2 (CEBPE) variation and risk of childhood ALL in the Polish population.
AB  - Recent studies have shown that SNPs mapping to 7p12.2 (IKZF1), 9p21 (CDKN2A),
      10q21.2 (ARID5B), and 14q11.2 (CEBPE) and carrier status for recessively
      inherited Nijmegen Breakage syndrome (NBS) influence childhood acute
      lymphoblastic leukemia (ALL) risk. To examine these relationship, we analysed 398
      ALL cases and 731 controls from Poland. Statistically significant association
      between genotype at 7p12.2 (IKZF1), 10q21.2 (ARID5B) and the NBS associated
      locus, 8q21.3 (NBN) and ALL risk was found; odds ratios (ORs), 1.34 (P=0.002),
      1.33 (P=0.003), and 1325.21 (P=0.0028), respectively. These data provide further
      insights into the biological basis of ALL highlighting the existence of both
      common and rare disease susceptibility variants.

PMID- 21889210
TI  - Interphase-FISH provides additional relevant information in myelodysplastic
      syndromes.

PMID- 21889211
TI  - Comparison of bioassays with different exposure time patterns: the added value of
      dynamic modelling in predictive ecotoxicology.
AB  - The purpose of this study was to compare Daphnia magna responses to cadmium
      between two toxicity experiments performed in static and flow-through conditions.
      As a consequence of how water was renewed, the two experiments were characterised
      by two different exposure time patterns for daphnids, time-varying and constant,
      respectively. Basing on survival, growth and reproduction, we addressed the
      questions of organism development and sensitivity to cadmium. Classical analysis
      methods are not designed to deal with the time dimension and therefore not
      suitable to compare effects of different exposure time patterns. We used instead
      a dynamic modelling framework taking all timepoints and the time course of
      exposure into account, making comparable the results obtained from our two
      experiments. This modelling framework enabled us to detect an improvement of
      organism development in flow-through conditions compared to static ones and infer
      similar sensitivity to cadmium for both exposure time patterns.

PMID- 21889212
TI  - Cytotoxicity of water-soluble fraction from biodiesel and its diesel blends to
      human cell lines.
AB  - The designation of biodiesel as a green fuel has increased its commercialization
      and use, making its fate in the environment a matter of concern. Fuel spills
      constitute a major source of aquatic pollution and, like diesel spills, biodiesel
      can produce adverse effects on aquatic environments, animals and humans. The
      present study assessed cytotoxic effects of water systems contaminated with neat
      biodiesel and its diesel blends by means of different procedures on human T cell
      leukemia (Jurkat) and human hepatocellular carcinoma (HepG2) cells [detection of
      changes in mitochondrial membrane potential (DeltaPsi(m)) using
      tetramethylrhodamine ethyl ester (TMRE), apoptosis recognition by Annexin V and
      impedance real-time cell analyzer (xCELLigenceTM system)]. The data obtained
      showed concordance across the different bioassays, with cytotoxic effects
      observed as a dose-dependent response only for waters contaminated with pure
      diesel (D100) and B5 blend, which is characterized by a mixture of 95% diesel and
      5% biodiesel. The data can also lead us to hypothesize that diesel accounts for
      the harmful effects observed, and that biodiesel does not worsen the impacts
      caused by diesel pollution.

PMID- 21889213
TI  - Phenomenology of psychotic mood disorders: lifetime and major depressive episode
      features.
AB  - BACKGROUND: The nosological and clinical implications of psychotic features in
      the course of mood disorders have been widely debated. Currently, no
      specification exists for defining a subgroup of lifetime Psychotic Mood Disorder
      (PMD) patients. METHODS: A total of 2178 patients were examined, including
      subjects with Bipolar Disorder (BP) type I (n=519) and II (n=207) and Major
      Depressive Disorder (n=1452). Patients were divided between PMD (n=645) and non
      psychotic Mood Disorders (MD) (n=1533) by the lifetime presence of at least one
      mood episode with psychotic features. Subjects having a depressive episode at the
      time of assessment were also examined: HAM-D and YMRS scores were compared
      between MD and PMD subjects, both with and without current psychotic features.
      RESULTS: A diagnosis of BP-I, a higher familial load for BP, a higher number of
      mood episodes lifetime, and a higher prevalence of OCD and somatic comorbidities
      were all associated to PMD. A diagnosis of BP (OR=4.48) was the only significant
      predictor for psychosis. PMD with non-psychotic depression were apparently less
      severe than MD patients and had a lower rate of "non-responders" to AD treatment.
      Sub-threshold manic symptoms and suicidal risk were also more pronounced among
      PMD. LIMITATIONS: The lack of information about number and polarity of previous
      psychotic mood episodes may be the major limitations of our study. CONCLUSIONS:
      BP diagnosis is the most significant predictor for psychosis in mood disorders.
      Non-psychotic mood episodes in PMD patients may be characterized by a distinctive
      symptom profile and, possibly, a different response to treatment.

PMID- 21889214
TI  - Targeting Toll-like receptors: emerging therapeutics for multiple sclerosis
      management.
AB  - Toll-like receptors (TLR) are important innate immune proteins for the
      identification and clearance of invading pathogen. TLR signal through adaptor
      proteins, most commonly myeloid differentiation primary response gene 88 (MyD88).
      Inappropriate response of specific TLR has been implicated in certain autoimmune
      diseases, such as multiple sclerosis (MS). Activation of TLR2, TLR4, TLR7 and
      TLR9 plays a role in experimental allergic encephalomyelitis (EAE), a murine
      model of MS, while TLR3 activation protects from disease. Therefore, TLR
      modulation could be an important adjuvant to current treatments. Here, we focus
      on TLR involved in EAE and MS pathogenesis highlighting specific components
      targeting TLR that might offer further therapeutic possibilities.

PMID- 21889215
TI  - IL28B polymorphisms are not associated with the response to interferon-beta in
      multiple sclerosis.
AB  - Recent studies have revealed an association between interleukin 28B (IL28B) and
      response to IFN-alpha treatment in hepatitis C patients. Here we investigated the
      influence of IL28B polymorphisms in the response to interferon-beta (IFNbeta) in
      multiple sclerosis (MS) patients. We genotyped two SNPs of the IL28B gene
      (rs8099917 and rs12979860) in 588 MS patients classified into responders (n=281)
      and non-responders (n=307) to IFNbeta. Combined analysis of the study cohorts
      showed no significant associations between SNPs rs8099917 and rs12979860 and the
      response to treatment. These findings do not support a role of IL28B
      polymorphisms in the response to IFNbeta in MS patients.

PMID- 21889216
TI  - Predicting complications after adenotonsillectomy in children 3 years old and
      younger.
AB  - OBJECTIVES: To identify risk factors for complications in the first 24h after
      surgery in the young (<4 years old) adenotonsillectomy patient. METHODS: A
      retrospective chart review was performed at a tertiary care children's hospital.
      Consecutive records of all children of age 3 years and younger undergoing
      adenotonsillectomy over a 5 year period were included in the study. The main
      outcomes measured were total and airway complications occurring on post-operative
      days 0-1. RESULTS: 993 patients were included in the study. The mean age was 2.94
      years old. Witnessed apneas (74.1%) and snoring (59.2%) were the most frequent
      pre-operative symptoms. 700 children were admitted with a mean length-of-stay of
      1.22 days (0-9 days) and a mean time-to-oral intake of 0.28 days (0-4 days) among
      those patients admitted. The total number of complications was 102 in 98 patients
      (9.9%). There were 35 complications on post-operative days (POD) 0-1 (3.5%), and
      23 of those were airway-related (2.3%). With regard to all complications on POD 0
      1, significant predictors were nasal obstruction, gastroesophageal reflux
      disease, prematurity and a history of cardiovascular anomalies. Significant
      predictors of airway complications on POD 0-1 were younger age (1-2 years old),
      larger adenoid size, nasal obstruction, and a history of cardiovascular
      anomalies. CONCLUSIONS: Knowing the stated risk factors for complications in the
      early post-operative period after adenotonsillectomy in the younger pediatric
      patient can help select certain patients for closer monitoring. Specifically,
      children aged 1-2 years old with a history of nasal obstruction from large
      adenoids, gastroesophageal reflux disease, prematurity, and/or cardiovascular
      anomalies appear to be at higher risk for early complications and should warrant
      closer observation.

PMID- 21889217
TI  - Endoscopic balloon dilatation of esophageal strictures in children.
AB  - AIM OF THE STUDY: To assess the efficacy and safety of endoscopic balloon
      dilatation of esophageal strictures in children. MATERIAL AND METHODS:  DESIGN:
      retrospective case series; population: 49 patients under 18 years of age referred
      to our center for esophageal strictures; treatment: endoscopic balloon
      dilatation; outcome parameters: residual dysphagia, weight gain, iatrogenic
      esophageal perforation, assessment of the esophageal lumen by endoscopy or
      esophagogram. RESULTS: The three main etiologies were esophageal atresia (49%;
      n=24), corrosive injury (25%; n=12), and epidermolysis bullosa (14%; n=7),
      followed by a heterogeneous group of rarer causes (12%; n=6). The number of
      dilatations ranged from 1 to 8 sessions per patient (median +/- SEM: 2 +/- 0.3).
      The length of the follow-up period ranged from 20 to 109 months (median +/- SEM:
      40 +/- 4 months). Treatment was successful in 86% of cases (n=42). Twelve percent
      of patients (n=6) had a residual stenosis requiring surgery, and a further one
      still experienced swallowing difficulties requiring enteral nutrition via
      gastrostomy in spite of the absence of significant residual stricture. Results
      were less satisfactory in cases of corrosive injury than with other etiologies.
      Three esophageal perforations were observed (6% of patients; 2% of procedures).
      All were medically treated. CONCLUSIONS: Endoscopic balloon dilatation is a
      simple, safe and efficacious treatment of esophageal strictures in children.

PMID- 21889218
TI  - Tissue remodeling in the acute otitis media mouse model.
AB  - OBJECTIVES: Otitis media is an infectious, inflammatory process involving the
      middle ear space. Chronic inflammation is associated with fibrosis, scarring and
      osteogenesis within the middle ear, which may contribute to subsequent hearing
      loss and increase the difficulty of treatment. METHODS: Heat-killed Streptococcus
      pneumoniae was injected into the middle ears of 8-12 week old Balb/c mice.
      Control mice were treated with PBS middle ear injections. Middle ears were
      harvested at 1, 3, 5 and 7 days following injection (n=8 for each time point).
      The middle ears were processed using standard RT-PCR techniques. Up- and down
      regulation of mRNA expression of various members of the Bone Morphogenetic
      Protein (BMP), Fibroblast Growth Factor (FGF) and Matrix Metalloproteinase (MMP)
      families was quantified and compared to PBS treated controls (n=8 for each time
      point). RESULTS: Significant upregulation of MMP2, MMP3 and MMP9 was observed at
      varying time points (p<0.05). Significant downregulation of BMP3, BMP4, BMP5 BMP6
      and BMP8a was seen at varying time points (p<0.05). Significant downregulation of
      FGF3, FGF6, FGF10 and FGFr1 was observed at varying time points (p<0.05). No
      significant expression of BMP8b, BMP9, BMP10, FGF5, FGF8, MMP1a, MMP7 and MMP14
      was detected within the middle ear. CONCLUSIONS: Inflammation within the middle
      ear following injection of bacterial products results in changes in the
      regulation of several tissue remodeling cytokines and proteinases in the mouse
      model. Further understanding of these molecular processes may allow for the
      development of treatment modalities aimed at preventing middle ear tissue
      remodeling.

PMID- 21889219
TI  - Age-related tonsillar regrowth in children undergoing powered intracapsular
      tonsillectomy.
AB  - OBJECTIVES: To review our experience with intracapsular tonsillectomy using
      powered instrumentation (PIT) in the management of tonsillar hypertrophy. DESIGN:
      Retrospective database review of pediatric patients undergoing PIT. METHODS: The
      medical records of 636 patients under 11 years of age who underwent PIT performed
      by the senior author (RFW), predominantly for obstructive sleep disturbance, were
      reviewed. Data were subsequently analyzed from 559 of these patients for clinical
      evidence of tonsillar regrowth, post-operative tonsillar hemorrhage, and post
      operative dehydration due to pain. Specific information for possible correlation
      of age at the time of surgery and any increased rate of regrowth was primarily
      examined. RESULTS: There were a total of 33 patients who had clinical evidence of
      regrowth. Children less than 5 years of age had 5 times the incidence of regrowth
      (p<0.001). Out of the group that exhibited regrowth, 5 patients exhibited
      evidence of recurrent upper airway obstruction and underwent a complete
      tonsillectomy. The age of this complete tonsillectomy group ranged from 1.1 to
      2.7 years. Out of all patients undergoing PIT, there was 1 incident of delayed
      post-operative dehydration due to emesis but not due to pain. There were 2
      incidents of delayed post-operative tonsillar bleeds. All three complications
      were self-limited and did not require re-hospitalization. CONCLUSIONS: PIT is a
      safe procedure with a small risk of tonsillar regrowth being age related. The
      incidence of postoperative complications following PIT is relatively low (0.54%).

PMID- 21889220
TI  - Caregiving of aged people, either professional job or acquiring merit in God's
      sight: an example of qualitative research.
AB  - Nowadays because of lots of reasons, lifespan is increasing and caregiving of
      aged people becomes more and more important. Today it is understood how the
      professional care of aged people is significant, instead of being carried out by
      volunteers. Because of this, in this study we aimed to understand the problems,
      and thoughts of aging of caregivers who are working in nursing homes. This study
      was made using the so-called qualitative research, which is one of the research
      designs. Including general aim, interviews with 13 caregivers with structured
      questions, supported by spontaneous ones. Interviews were taped and transcribed
      verbatim. After that, they were grouped with the same themes. Thoughts are
      grouped with three main themes, which are about "aging", "working life",
      "caregiving of aged people". Aged people are described like people who are
      dependent, need interest, and represent the wisdom period. Also caregiving is
      described like both good job and punishment. Besides, the reason of working as a
      caregiver, is the economic needs. The suggestions of caregivers are increasing
      payment, giving psychological and emotional support, and also improving physical
      conditions. Economic satisfaction of caregivers, giving psychological support,
      caregivers with aged people and improving physical conditions are important to
      increase the quality of professional caregiving.

PMID- 21889221
TI  - Prostate HDR brachytherapy catheter displacement between planning and treatment
      delivery.
AB  - BACKGROUND AND PURPOSE: HDR brachytherapy is used as a conformal boost for
      treating prostate cancer. Given the large doses delivered, it is critical that
      the volume treated matches that planned. Our outpatient protocol comprises two 9
      Gy fractions, two weeks apart. We prospectively assessed catheter displacement
      between CT planning and treatment delivery. MATERIALS AND METHODS: Three fiducial
      markers and the catheters were implanted under transrectal ultrasound guidance.
      Metal marker wires were inserted into 4 reference catheters before CT; marker
      positions relative to each other and to the marker wires were measured from the
      CT scout. Measurements were repeated immediately prior to treatment delivery
      using pelvic X-ray with marker wires in the same reference catheters.
      Measurements from CT scout and film were compared. For displacements of 5mm or
      more, indexer positions were adjusted prior to treatment delivery. RESULTS:
      Results are based on 48 implants, in 25 patients. Median time from planning CT to
      treatment delivery was 254 min (range 81-367 min). Median catheter displacement
      was 7.5mm (range -2.9-23.9 mm), 67% of implants had displacement of 5mm or
      greater. Displacements were predominantly caudal. CONCLUSIONS: Catheter
      displacement can occur in the 1-3h between the planning CT scan and treatment. It
      is recommended that departments performing HDR prostate brachytherapy verify
      catheter positions immediately prior to treatment delivery.

PMID- 21889222
TI  - Young age under 60 years is not a contraindication to treatment with definitive
      dose escalated radiotherapy for prostate cancer.
AB  - BACKGROUND: It is widely believed that younger prostate cancer patients are at
      greater risk of recurrence following radiotherapy (RT). METHODS: From 1992 to
      2007, 2168 (395 age <= 60) men received conformal RT alone for prostate cancer at
      our institution (median dose=76 Gy, range: 72-80). Multivariable analysis (MVA)
      was used to identify significant predictors for BF and PCSM. Cumulative incidence
      was estimated using the competing risk method (Fine and Gray) for BF (Phoenix
      definition) and PCSM to account for the competing risk of death. RESULTS: With a
      median follow-up of 72.2 months (range: 24.0-205.1), 8-year BF was 27.1% for age
      <= 60 vs. 23.7% for age >60 (p=0.29). Eight-year PCSM was 3.0% for age <= 60 vs.
      2.0% for age >60 (p=0.52). MVA for BF identified initial PSA [adjusted HR=1.7
      (PSA 10-20), 2.6 (PSA >20), p<0.01], Gleason score [adjusted HR=2.1 (G7), 1.9 (G8
      10), p<0.01], T-stage [adjusted HR=1.7 (T2b-c), 2.6 (T3-4), p<0.01], and initial
      androgen deprivation therapy (ADT) [adjusted HR=0.38 (ADT >12 months), p<0.01] as
      significant, but not age or ADT <12 months. MVA for PCSM identified Gleason score
      [adjusted HR=3.0 (G8-10), p=0.01] and T-stage [adjusted HR=8.7 (T3-4), p<0.01] as
      significant, but not age, PSA, or ADT. CONCLUSION: This is the largest, most
      mature study of younger men treated with RT for prostate cancer that confirms
      young age is not prognostic for BF.

PMID- 21889223
TI  - Oncologists' view of informed consent and shared decision making in paediatric
      radiation oncology.
AB  - BACKGROUND AND PURPOSE: Cure rates of paediatric malignancies have dramatically
      improved with therapy intensification, at the cost of late treatment side
      effects. A survey was developed, centred around medulloblastoma scenarios, in
      order to explore paediatric oncology physicians' views on discussing late effects
      and involving parents in treatment decisions. MATERIALS AND METHODS: Participants
      were 59 paediatric radiation and medical oncologists or fellows from USA (22),
      Canada (18), Europe (16), Australia (2), and Asia (1). RESULTS: Ninety-five
      percent of respondents indicated late effects discussion prior to multimodality
      treatment was important. Of those who supported it, 100%, 83%, 64%, and 48%
      thought discussing cognitive impairment, infertility, stroke, and seizures as
      potential late effects was important, respectively. Only 71% of respondents
      believed parents should be involved in treatment decisions, which did not
      significantly vary by respondent age, country, specialty, gender, or years in
      practice. CONCLUSIONS: The majority of oncologists who treat children believe
      discussing late effects with parents is important. However, there is mixed
      opinion on which late effects should be discussed and whether parents should be
      involved in deciding which treatments should be pursued. Research into perceived
      barriers to shared decision making and effective methods of improving the
      informed consent process in paediatric malignancies is needed.

PMID- 21889224
TI  - The maximum standardized uptake value (SUVmax) on FDG-PET is a strong predictor
      of local recurrence for localized non-small-cell lung cancer after stereotactic
      body radiotherapy (SBRT).
AB  - BACKGROUND: The maximum standardized uptake value (SUVmax) of FDG-PET may predict
      local recurrence for localized non-small-cell lung cancer (NSCLC) after
      stereotactic body radiotherapy (SBRT). METHODS: Among 195 localized NSCLCs that
      were treated with total doses of either 40Gy or 50Gy in 5 SBRT fractions, we
      reviewed those patients who underwent pre-treatment FDG-PET using a single
      scanner for staging. Local control rates (LCRs) were obtained by the Kaplan-Meier
      method and a log-rank test. Prognostic significance was assessed by univariate
      and multivariate analyses. RESULTS: A total of 95 patients with 97 lesions were
      eligible. Median follow-up was 16.0months (range: 6.0-46.3months). Local
      recurrences occurred in 9 lesions. By multivariate analysis, only the SUVmax of a
      primary tumor was a significant predictor (p=0.002). Two years LCRs for lower
      SUVmax (<6.0; n=78) and higher SUVmax (?6; n=19) were 93% and 42%, respectively.
      In subgroups with T1b and T2, LCRs were significantly better for lower SUVmax
      than for higher SUVmax (p<0.0005 and p<0.01). In both subgroups that received
      40Gy and 50Gy, LCRs were also significantly better for lower SUVmax than for
      higher SUVmax (p<0.001 and p<0.01). CONCLUSIONS: SUVmax was the strongest
      predictor for local recurrence. A high SUVmax may be considered for dose
      escalation to improve local control. Additional follow-up is needed to determine
      if SUVmax is correlated with regional recurrence, distant metastasis, and
      survival.

PMID- 21889225
TI  - Radiotherapy treatment of keloid scars with a kilovoltage X-ray parallel pair.
AB  - An established treatment for keloids is surgery and radiotherapy, using a single
      applied field. However, earlobe keloids lend themselves to a parallel opposed
      pair approach. Delivery with a superficial X-ray unit is practicable and improves
      homogeneity within the treatment volume. It has been implemented in this centre
      since 2007.

PMID- 21889226
TI  - Genotyping and phenotyping of Fusarium graminearum isolates from Germany related
      to their mycotoxin biosynthesis.
AB  - Fusarium graminearum is the most important pathogen causing Fusarium head blight
      (FHB) of small cereal grains worldwide responsible for quantitative and
      qualitative yield losses. The presence in crops is often associated with
      mycotoxin contamination of foodstuff limiting its use for human and animal
      consumption. A collection of isolates of F. graminearum from Germany was
      characterized genetically and chemically for their potential to produce the B
      trichothecenes deoxynivalenol (DON) and nivalenol (NIV). Molecular methods with
      eight PCR assays were implemented based on functional Tri7 and Tri13 genes and on
      the tri5-tri6 intergenic region to differentiate between chemotaxonomic groups
      DON and NIV, resulting in a marked majority (61/63) of DON chemotypes. Mycotoxins
      produced on rice kernels were quantified by means of LC-MSMS including DON, NIV,
      3-acetyl-DON (3-ADON), 15-acetyl-DON (15-ADON), DON-3-glucoside, fusarenon X, as
      well as zearalenone; all of them proving to be present in high concentration
      among the isolates. All DON-chemotype isolates also produced lower amounts of NIV
      with the amount being positively correlated (R2=0.89) to the DON amount. 15-ADON
      and 3-ADON are reported to be produced simultaneously by the isolates, the former
      dominating over the latter in all but one isolate. Fungal biomass, was quantified
      via ergosterol amount on rice. It was used to calculate specific mycotoxin
      production per biomass of isolates, ranging from 0.104 to 1.815mg DON mg-1
      ergosterol, presenting a Gaussian distribution. Genotype and phenotype
      characterization revealed discrepancies with respect to mycotoxin production
      potential of the fungi, i.e. isolates from one chemotype were able to produce
      mycotoxins from other chemotypes in considerable amounts.

PMID- 21889227
TI  - RRM1 expression and clinical outcome of gemcitabine-containing chemotherapy for
      advanced non-small-cell lung cancer: a meta-analysis.
AB  - BACKGROUND: The predictive value of RRM1 to therapeutic efficacy of gemicitabine
      containing chemotherapy in patients with advanced non-small-cell lung cancer
      (NSCLC) remains disputable. This meta-analysis is performed to systematically
      evaluate whether RRM1 expression is associated with the clinical outcome of
      gemcitabine-containing regimen in advanced NSCLC. METHODS: An electronic search
      was conducted using the databases Pubmed, Medline, EMBASE, Cochrane library and
      CNKI, from inception to May, 2011. A systemic review of the studies on the
      association between RRM1 expression in advanced NSCLC and clinical outcome of
      gemcitabine-containing regimen was performed. Pooled odds ratios (OR) for the
      response rate, weighted median survival and time to progression were calculated
      using the software Revman 5.0. RESULTS: The search strategy identified 18
      eligible studies (n=1243). Response rate to gemcitabine-containing regimen was
      significantly higher in patients with low/negative RRM1 (OR=0.31, 95% CI 0.21
      0.45, P<0.00001). NSCLC patients with low/negative RRM1 who were treated with
      gemicitabine-containing regimen survived 3.94 months longer (95% CI 2.15-5.73,
      P<0.0001) and had longer time to progression for 2.64 months (95% CI 0.39-4.89,
      P=0.02) than those with high/positive RRM1. CONCLUSIONS: Low/negative RRM1
      expression in advanced NSCLC was associated with higher response rate to
      gemcitabine-containing regimen and better prognosis. Large phase III randomized
      trials are required to identify whether RRM1 detection is clinically valuable for
      predicting the prognosis and sensitivity to gemcitabine-containing regimen in
      advanced NSCLC.

PMID- 21889228
TI  - Systems biology of infectious diseases: a focus on fungal infections.
AB  - The study of infectious disease concerns the interaction between the host species
      and a pathogen organism. The analysis of such complex systems is improving with
      the evolution of high-throughput technologies and advanced computational
      resources. This article reviews integrative, systems-oriented approaches to
      understanding mechanisms underlying infection, immune response and inflammation
      to find biomarkers of disease and design new drugs. We focus on the systems
      biology process, especially the data gathering and analysis techniques rather
      than the experimental technologies or latest computational resources.

PMID- 21889229
TI  - Topical versus peribulbar anesthesia in non-penetrating deep sclerectomy. A cost
      effectiveness analysis.
AB  - AIM: To assess the costs and cost-effectiveness ratio of topical and peribulbar
      anesthesia in non-penetrating deep sclerectomy for the surgical treatment of open
      angle glaucoma. PATIENTS AND METHODS: We evaluated the associated direct costs
      with both topical and peribulbar anesthesia. Effectiveness was defined as the
      proportion of patients that experienced no pain during the surgical procedure and
      was obtained from the literature. Cost-effectiveness was defined as direct cost
      of anesthesia per patient with no pain. We also calculated the incremental cost
      effectiveness ratio (ICER) in order to determine which intervention was dominant.
      RESULTS: Direct costs were US$ 45.60 and US$ 49.18 for topical and peribulbar
      anesthesia respectively. The great majority of patients experienced no pain with
      any of the procedures (91.7% for the topical group and 69.7% for the peribulbar
      group). Cost-effectiveness ratio was US$ 49.73 for topical anesthesia and US$
      70.56 for peribulbar anesthesia. The ICER was negative and topical anesthesia was
      dominant over peribulbar anesthesia. CONCLUSION: Topical anesthesia was less
      costly and more effective than peribulbar anesthesia in avoiding pain in non
      penetrating deep sclerectomy.

PMID- 21889230
TI  - [Anti-TNF-alpha in the treatment of uveitis in the Besancon Hospital].
AB  - BACKGROUND: Noninfectious chronic uveitis is a difficult-to-treat situation in
      which corticosteroids, immunosuppressive agents, and more recently, anti-tumor
      necrosis factor (TNF)-alpha are used to prevent and/or reverse severe visual
      impairment. This single-center retrospective study was designed to assess the use
      (indications, efficacy, and side effects) of anti-TNF-alpha agents in
      noninfectious uveitis. PATIENTS AND METHODS: Eight patients were analyzed: three
      children (age, 7-15 years) and five adults (age, 27-44 years). Anti-TNF-alpha
      agents were etanercept (three patients), adalimumab (four patients), and
      infliximab (four patients). Diagnoses were Behcet's diseases (n=3), sarcoidosis
      (n=1), juvenile chronic arthritis (n=2), spondyloarthropathy (n=2), one of the
      latter two combined with Crohn disease. In all cases, anti-TNF-alpha therapies
      were prescribed because uveitis and/or associated disease were not under control.
      RESULTS: Adalimumab and infliximab were effective for all patients. One patient
      with infliximab needed to add corticosteroids and immunosuppressive agents
      because of relapse. Etanercept was stopped in all cases due to a lack of
      effectiveness or a change in indication. In all patients, anti-TNF-alpha agents
      improved uveitis and the underlying systemic disease. In children, their use
      improved quality of life by corticosteroid weaning. Prescriptions did not comply
      with regulations for three children, because of age limits (etanercept, one;
      adalimumab, two). No adverse event was recorded. CONCLUSION: In this short case
      series, anti-TNF-alpha agents were effective both on uveitis and the underlying
      systemic disease and were well tolerated in patients with noninfectious chronic
      uveitis.

PMID- 21889231
TI  - [Peritoneal strumosis: an extension study with (99m)Tc-pertecnectate].
AB  - We report the case of a 35-year-old nulliparous woman, with a previous history of
      ovarian cystectomy diagnosed 3 years earlier due a struma ovarii type of
      monodermal teratoma in the right ovary and a hemorrhagic cyst in the left ovary.
      Progressive growth of the left adnexal mass was observed in the periodic medical
      check-ups. Due to this, a second laparoscopy was performed and, based on the
      findings, a left ovarian cystectomy, right salpingectomy and resection of
      multiple peritoneal implants were carried out. The pathology diagnosis was left
      struma ovarii and peritoneal strumosis. A whole body and SPECT/CT scan with
      (99m)Tc-pertechnetate was performed to detect possible peritoneal implants. This
      study helped to make the therapeutic decision.

PMID- 21889232
TI  - [FOTOTRANS study: multicentre study on the validity of Fototest under clinical
      practice conditions].
AB  - OBJECTIVE: Fototest is a short simple test, applicable to illiterate subjects and
      not influenced by educational level. The purpose of this study is to assess its
      validity for cognitive impairment (CI) and dementia (DEM) under routine clinical
      practice conditions. MATERIAL AND METHODS: A cross-sectional, multicentre and
      naturalistic study conducted in General Neurology clinics. The subjects were,
      over 60 years old, with a previously established diagnosis of no cognitive
      impairment (NoCI), cognitive impairment without dementia (CInoDEM), or dementia
      (DEM). The discriminant validity was assessed using the area under the ROC curve
      (AUC), sensitivity (Sn), specificity (Sp), and probability coefficients. Partial
      correlations were calculated, adjusted for age, sex and education level with
      Eurotest, verbal fluency test (VFT) and Global Deterioration Scale (GDS) score to
      evaluate the concurrent and construct validity. RESULTS: Nineteen neurologists
      included a total of 589 subjects: 361 NoCI, 106 CINoDEM and 122 DEM. The
      discriminant value was better for DEM (AUC 0.94 +/- 0.02) than for CI (0.86 +/-
      0.02). For DEM the best cut-off point was 26/27 (Sn=0.88 [95% CI, 0.93-0.97],
      Sp=0.87 [95% CI, 0.84-0.90]); and for CI, 28/29 (Sn=0.71 [95% CI, 0.65-0.77],
      Sp=0.84 [95% CI, 0.80-0.88]). Fototest showed a high and significant correlation
      with Eurotest (r=0.70 +/- 0.02), VFT (r=0.68 +/- 0.02) and the GDS score (r=-0.77
      +/- 0.02). CONCLUSION: The Fototest showed adequate validity for CI and DEM in
      general Neurology clinics in an extensive and wide geographical area.

PMID- 21889233
TI  - [Migraine associated with conversion symptoms (Babinski's migraine): evaluation
      of a series of 43 cases].
AB  - BACKGROUND: In 1890 four cases of headache associated with visual symptoms and
      hysterical disorder were described by the French neurologist Babinski as migraine
      ophthalmique hysterique, or hysterical ophthalmic migraine. Since that time this
      association has seldom been described, and the possibly high frequency previously
      reported still remains to be established. This paper has reused Babinski's
      description and it tries to rehabilitate the syndrome described by the French
      semiologist across the relatively frequent experience of this type of patients in
      a public hospital. Also it analyzes the reason of the oblivion of his
      description. METHOD: This study presents a series of 43 cases of headache of the
      migraine type associated with other symptoms, most consistent with basilar-type
      migraine according to IHS criteria. Diagnosis of conversion disorder (hysteria)
      was grounded in the criteria set forth in the DSM-IV. RESULTS: All patients
      exhibited one or more manifestations of hysteria (conversion symptoms) during
      migraine attacks, and some did in the intervals between attacks as well. Details
      of the headaches, associated symptoms, and hysterical manifestations are
      discussed. Most patients improved with antimigraine medication. Altered
      consciousness may have contributed to the onset of hysterical symptoms.
      CONCLUSIONS: The basilar type migraine associated with conversion symptoms
      described of systematized form by Babinski, it is not a rare entity. Similar
      pictures have been described along the history of the medicine. The later silence
      possibly is due to the historical difficulty in defining accurately the
      conversion disorders. The Babinskis migraine is a certain well entity and must be
      recovered for the clinic.

PMID- 21889235
TI  - Discovery of gemfibrozil analogues that activate PPARalpha and enhance the
      expression of gene CPT1A involved in fatty acids catabolism.
AB  - A new series of gemfibrozil analogues conjugated with alpha-asarone, trans
      stilbene, chalcone, and their bioisosteric modifications were synthesized and
      evaluated to develop PPARalpha agonists. In this attempt, we have removed the
      methyls on the phenyl ring of gemfibrozil and introduced the above scaffolds in
      para position synthesizing two series of derivatives, keeping the
      dimethylpentanoic skeleton of gemfibrozil unaltered or demethylated. Four
      compounds exhibited good activation of the PPARalpha receptor and were also
      screened for their activity on PPARalpha-regulated gene CPT1A.

PMID- 21889234
TI  - [Low sensitivity of the echocardiograph compared with contrast transcranial
      Doppler in right-to-left shunt].
AB  - BACKGROUND: Contrast transcranial Doppler (c-TCD) has a high sensitivity for
      detecting right-to-left shunt (RLS), and is probably higher than transthoracic
      echocardiography (TTE) and comparable with transesophageal echocardiography
      (TEE). OBJECTIVE: To evaluate the accuracy of echocardiography (TTE and TEE) to
      detect RLS compared to c-TCD. MATERIAL AND METHODS: Observational study of
      patients <55 years old with cerebral ischaemia of undetermined origin (2007
      2009). All underwent c-TCD monitoring to detect RLS, at rest and after Valsalva
      manoeuvre (VM). The TTE and TEE were performed when indicated by our
      cerebrovascular protocol. The accuracy of TTE and TEE for detecting RLS was
      calculated by comparing them with c-TCD. RESULTS: A total of 115 patients with c
      TCD, mean age 43.3 (SD 10.3) years, 51.3% male. The TTE was performed in 102, and
      TEE in 81, patients. RLS detection was higher with c-TCD than with TTE (67.6% vs.
      22.5%, P=.001) or TEE (77.8% vs. 53.1%, P=.001). The TTE, compared with c-TCD
      after MV showed: sensitivity 31.8%, specificity 96.9%, positive predictive value
      (PPV) 95.6%, negative predictive value (NPV) 40.5% and accuracy 52.9% to detect
      RLS. TEE, compared with c-TCD after MV showed: sensitivity 63.4%, specificity
      83.3%, PPV 93%, NPV 39.4% and accuracy 67.9%. The accuracy of TTE and TEE
      improved when they were compared with c-TCD at rest. CONCLUSIONS: TTE and TEE
      show a considerable number of false negatives for RLS detection. Clinical studies
      should consider the c-TCD as the best technique to diagnose RLS when a
      paradoxical embolism is suspected.

PMID- 21889236
TI  - Synthesis, stereochemistry and SAR of a series of minodronate analogues as RGGT
      inhibitors.
AB  - Phosphonocarboxylate (PC) analogues of bisphosphonates are of interest due to
      their selective inhibition of a key enzyme in the mevalonate pathway, Rab
      geranylgeranyl transferase (RGGT). The dextrarotatory enantiomer of 2-hydroxy-3
      (imidazo[1,2-a]pyridin-3-yl)-2-phosphonopropanoic acid (3-IPEHPC, 1) is the most
      potent PC-type RGGT inhibitor thus far identified. The absolute configuration of
      (+)-1 in the active site complex has remained unknown due to difficulties in
      obtaining RGGT inhibitor complex crystals suitable for X-ray diffraction
      analysis. However, we have now succeeded in crystallizing (-)-1 and here report
      its absolute configuration (AC) obtained by X-ray crystallography, thus also
      defining the AC of (+)-1. An Autodock Vina 1.1 computer modeling study of (+)-1
      in the active site of modified RGGT binding GGPP (3DSV) identifies
      stereochemistry-dependent interactions that could account for the potency of (+)
      1 and supports the hypothesis that this type of inhibitor binds at the TAG
      tunnel, inhibiting the second geranylgeranylation step. We also report a
      convenient (31)P NMR method to determine enantiomeric excess of 1 and its pyridyl
      analogue 2, using alpha- and beta-cyclodextrins as chiral solvating agents, and
      describe the synthesis of a small series of 1 alpha-X (X = H, F, Cl, Br; 7a-d)
      analogues to assess the contribution of the alpha-OH group to activity at enzyme
      and cellular levels. The IC(50) of 1 was 5-10* lower than 7a-d, and the LED for
      inhibition of Rab11 prenylation in vitro was 2-8* lower than for 7a-d. However,
      in a viability reduction assay with J774 cells, 1 and 7b had similar IC(50)
      values, ~10* lower than those of 7a and 7c-d.

PMID- 21889237
TI  - Learning styles of first-year undergraduate nursing and midwifery students: a
      cross-sectional survey utilising the Kolb Learning Style Inventory.
AB  - It is important that educators understand their students' learning styles. In
      this study we investigate the learning styles of first-year undergraduate nursing
      and midwifery university students and whether these learning styles are
      influenced by student demographic characteristics. A cross-sectional survey
      including demographic questions and the Kolb Learning Style Inventory was
      utilised. There was a 78% response rate (n=345). The majority of first-year
      students investigated in this study were divergers (29.5%), followed by
      assimilators (28.8%), accommodators (23.9%) and convergers (17.9%). Female
      students had a higher reflective observation (RO) score than male students
      (p=0.0078). Those with English as first language showed a higher active
      experimentation score (p=0.0543) and a lower concrete experience (CE) score
      (p=0.0038). Australian citizens and permanent residents had a higher RO score
      (p=0.0560) and a lower CE score (p=0.0100) than migrants and international
      students. Nursing/arts students had a higher abstract conceptualisation (AC)
      score than nursing students (p=0.0013). Students enrolled in 4-5 subject units
      had a higher AC score than those enrolled in 1-2 units (p=0.0244). Nursing and
      midwifery students are mainly of the diverger and assimilating learning styles.
      Some student demographic characteristics show a significant influence on learning
      styles. This study has teaching and research implications.

PMID- 21889238
TI  - Estimating and predicting chemical potentials, distributions, speciation modes
      and mobilities of radiometals in soil, water and biomass.
AB  - Using a method from coordination chemistry, which is linked to ligand field
      theory, the interaction of (binding of) metal ions with biomass is described and
      put to quantitative scales including bioconcentration factors for a given living
      being. This can be extended to radionuclides and biological exposure to them.
      Fractionation of radionuclides from fission in biomass is discussed in examples
      from various taxonomic groups, also touching issues of possible human exposure.

PMID- 21889239
TI  - Potential risks: Re: a method for the extraction of impacted upper third molars.

PMID- 21889240
TI  - The effects of walking sticks on gait kinematics and kinetics with chronic stroke
      survivors.
AB  - BACKGROUND: There are robust clinical paradigms against the prescription of
      walking sticks for people with stroke. However, there is little information on
      the biomechanics of gait with and without these devices to guide clinical
      practice. Therefore, this study investigated how the use of walking sticks (canes
      or crutches) affected both the kinematics and kinetics of gait in people with
      chronic stroke after their walking had stabilized. METHODS: Nineteen people with
      chronic stroke walked at both comfortable and fast speeds. A 3-D motion analysis
      system and one force platform were used to obtain kinematic and kinetic data of
      the paretic lower limb during four conditions: With and without walking sticks,
      and at comfortable and fast speeds. Outcomes included linear kinematics (walking
      speeds) and angular kinematics (maximum joint angles), power, and work of the
      paretic hip, knee and ankle joints in the saggital plane. FINDINGS: The use of
      walking sticks resulted in increases in speed during both fast (P<0.001) and
      comfortable (P=0.001) walking, but did not result in changes in maximum joint
      angles. This also led to increases in ankle plantar flexion (P<0.01), knee
      extension (P<0.01), and hip flexion (P<0.001) power generation, but did not
      result in changes in work. There were no greater changes as a result of using
      walking sticks during fast versus comfortable walking for any outcome.
      INTERPRETATIN: The outcomes with the use of walking sticks were beneficial, which
      suggests that the prescription of these devices is not detrimental to walking
      that was stabilized in people with stroke.

PMID- 21889241
TI  - Dynamic Balance Control (DBC) in lower leg amputee subjects; contribution of the
      regulatory activity of the prosthesis side.
AB  - BACKGROUND: Regaining effective postural control after lower limb amputation
      requires complex adaptation strategies in both the prosthesis side and the non
      amputated side. The objective in this study is to determine the individual
      contribution of the ankle torques generated by both legs in balance control
      during dynamic conditions. METHODS: Subjects (6 transfemoral and 8 transtibial
      amputees) stood on a force platform mounted on a motion platform and were
      instructed to stand quietly. The experiment consisted of 1 static and 3
      perturbation trials of 90 s duration each. The perturbation trials consisted of
      continuous randomized sinusoidal platform movements of different amplitude in the
      sagittal plane. Weight distribution during the static and dynamic perturbation
      trials was calculated by dividing the average vertical force below the prosthesis
      foot by the sum of forces below both feet. The Dynamic Balance Control represents
      the ratio between the stabilizing mechanism of the prosthetic leg and the
      stabilizing mechanism of the non-amputated leg. The stabilizing mechanism is
      calculated from the corrective ankle torque in response to sway. The relationship
      between the prosthetic ankle stiffness and the performance during the platform
      perturbations was calculated. FINDINGS: All patients showed a (non-significant)
      weight bearing asymmetry in favor of the non-amputated leg. The Dynamic Balance
      Control ratio showed that the contribution of both legs to balance control was
      even more asymmetrical. Moreover, the actual balance contribution of each leg was
      not tightly coupled to weight bearing in each leg, as was the case in healthy
      controls. There was a significant positive correlation between the prosthetic
      ankle stiffness and the Dynamic Balance Control. INTERPRETATION: The Dynamic
      Balance Control provides, in addition to weight distribution, information to what
      extent the stabilizing mechanism of the corrective ankle torque of both legs
      contributes to balance control. Knowledge of the stiffness properties may
      optimize the prescription process of prosthetic foot in lower leg amputee
      subjects in relation to standing stability.

PMID- 21889242
TI  - Dynamic impression insole in rheumatoid foot with metatarsal pain.
AB  - BACKGROUND: Custom molded insoles with metatarsal supports are used to
      redistribute excessive loading under the metatarsal heads in patients with
      metatarsalgia. However, these pressure reductions are usually insufficient for
      the rheumatoid foot with painful deformed metatarsal heads. We developed an
      effective insole made by sequential foam padding under successive walking
      impression. METHODS: Seventeen consecutive rheumatoid arthritic outpatients with
      metatarsal pain participated in this repeated measures study of 7-mm flat
      Ethylene Vinyl Acetate, custom molded and dynamic impression insoles. Peak
      plantar pressure, pressure-time integral, contact area and mean force were
      measured by a Pedar-X mobile system. Pain levels were assessed using a Visual
      Analog Scale (0-10). FINDINGS: Compared to the Ethylene Vinyl Acetate control,
      the metatarsal head peak pressure and pressure-time integral were significantly
      reduced in dynamic impression insoles by 46.3% (P<0.001) and 48.9% (P<0.001),
      respectively. Compared to the custom molded insole, the dynamic impression insole
      significantly reduced 18.3% of peak pressure (P<0.001) and 20.1% of pressure-time
      integral (P<0.001) by increasing 8.1% of contact area (P=0.005) at the metatarsal
      heads, but there were no significant differences in all variables at the heel.
      After using the dynamic impression insole, the mean pain score was significantly
      reduced from 7.6 to 1.1 (P<0.001), and six participants experienced total pain
      relief in walking. INTERPRETATION: Dynamic impression insoles effectively relieve
      metatarsal pain because of a larger weight-bearing area. Forefoot shape during
      walking should be taken into consideration in orthotic designs for maximum
      pressure reduction. Consequently, we recommend using materials with memory
      properties to dynamically accommodate painful metatarsal heads.

PMID- 21889243
TI  - Primary stability and strain distribution of cementless hip stems as a function
      of implant design.
AB  - BACKGROUND: Short stem prostheses have been developed to preserve the femoral
      bone stock. The purpose of this study was to evaluate the stress-shielding effect
      in the proximal femur as well as the micromotion between bone and implant as a
      measure of primary stability for a new short stem in comparison to a clinically
      successful short stem and a straight stem. METHODS: Using paired fresh human
      femurs, stress shielding was examined by using tri-axial strain gage rosettes.
      The strain distribution of the proximal femur was measured before and after
      implantation of three cementless prostheses of different design concepts and stem
      lengths. Furthermore, interface motion and rotational stability were investigated
      under dynamic loading (100-1600 N) after 100,000 load cycles using inductive
      miniature displacement transducers. FINDINGS: A reduction of longitudinal
      cortical strains in the proximal femur was displayed for all three implants. The
      reduction was less pronounced for the shorter stem implants, however. Interface
      motion was below the critical threshold of 150 MUm at almost all measuring points
      for all three stems, with a tendency for greater rotational stability in the
      shorter stem implants. INTERPRETATION: The new short stem prosthesis displayed
      reduced stress shielding and comparable primary stability to an established short
      stem and a conventional shaft design. Shortening the stem did not negatively
      influence primary stability. The clinical implications of these findings remain
      to be proven.

PMID- 21889244
TI  - Relationship between (210)Pb(ex) activity and sedimentary organic carbon in
      sediments of 3 Chinese lakes.
AB  - This report demonstrates that organic matter was an important factor in lake
      sediment (210)Pb(ex) dating. Sediment cores from lakes in central and western
      China with different-trophic levels were collected, and the (210)Pb(ex) activity
      and total organic carbon (TOC) were measured. The Rock-Eval pyrolysis technique
      was used to deconvolute TOC into free hydrocarbons (S1), thermally less-stable
      macromolecular organic matter (S2a), kerogen (S2b), and residual carbon (RC). The
      results show significant correlations between TOC and (210)Pb(ex), particularly
      between S2a and (210)Pb(ex), in all the sediment cores. This indicated that the
      algal-derived organic component S2a may play the most important role in
      controlling the distribution of (210)Pb(ex). Scavenging by algal-derived organic
      matter may be the main mechanism. As chronology is the key to the understanding
      of pollution reconstruction and early diagenesis in sediments, more attention
      should be paid to the influence of organic matter on (210)Pb(ex).

PMID- 21889245
TI  - Long-term mercury dynamics in UK soils.
AB  - A model assuming first-order losses by evasion and leaching was used to evaluate
      Hg dynamics in UK soils since 1850. Temporal deposition patterns of Hg were
      constructed from literature information. Inverse modelling indicated that 30% of
      898 rural sites receive Hg only from the global circulation, while in 51% of
      cases local deposition exceeds global. Average estimated deposition is 16 MUg Hg
      m(-2) a(-1) to rural soils, 19 MUg Hg m(-2) a(-1) to rural and non-rural soils
      combined. UK soils currently hold 2490 tonnes of reactive Hg, of which 2140
      tonnes are due to anthropogenic deposition, mostly local in origin. Topsoil
      currently releases 5.1 tonnes of Hg(0) per annum to the atmosphere, about 50%
      more than the anthropogenic flux. Sorptive retention of Hg in the lower soil
      exerts a strong control on surface water Hg concentrations. Following decreases
      in inputs, soil Hg concentrations are predicted to decline over hundreds of
      years.

PMID- 21889246
TI  - Impact of motivation on cognitive control in the context of vigilance lowering:
      an ERP study.
AB  - We assessed the effects of time-on-task on cognitive control expressed by the
      CRN/Nc and the extent to which motivation modulates this relationship. We
      utilized two groups of participants, who were told that their performance would
      (evaluation condition) or would not (control condition) be evaluated online. Both
      groups performed a version of the Eriksen Flanker Task for 60 min. We observed
      classical vigilance lowering, manifested by a progressive performance decline
      with time-on-task, in the control, but not in the evaluation, condition. In the
      latter, performance remained stable throughout the task. ERP analysis indicated
      the same interaction in our main component of interest, the CRN/Nc, whose
      amplitude decreased from the first to the last period in the control condition
      but remained stable over time in the evaluation condition. To our knowledge, this
      study is the first to demonstrate the impact of motivation on monitoring
      processes as indexed by the correct response negativity, in the context of a
      prolonged task. Vigilance lowering caused by a repetitive and prolonged flanker
      task, results in compromised response control and compromised control of correct
      responses. Our results suggest that alterations in ACC functioning may underlie
      vigilance decline and can be viewed as evidence that the action monitoring
      functions of the ACC can be positively affected by motivation.

PMID- 21889247
TI  - Association of the DAT1 genotype with inattentive behavior is mediated by reading
      ability in a general population sample.
AB  - Attention deficit hyperactivity disorder (ADHD) and reading disability (RD)
      frequently co-occur in the child population and therefore raise the possibility
      of shared genetic etiology. We used a quantitative trait loci (QTL) approach to
      assess the involvement of the dopamine transporter (DAT1) gene polymorphism in
      mediating reading disability and poor attention in a general population sample of
      primary school children aged 6-11 years in the UK. The potential confounding
      effects of IQ and chronological age were also investigated. We found an
      independent association between the homozygous DAT1 10/10 repeat genotype and RD
      that was not accounted for by the level of ADHD symptoms. This finding suggests
      that the DAT1 gene polymorphism may influence a common neural mechanism
      underlying both reading acquisition and ADHD symptoms.

PMID- 21889248
TI  - Increased spreading activation in depression.
AB  - The dopaminergic system is implicated in depressive disorders and research has
      also shown that dopamine constricts lexical/semantic networks by reducing
      spreading activation. Hence, depression, which is linked to reductions of
      dopamine, may be associated with increased spreading activation. However,
      research has generally found no effects of depression on spreading activation,
      using semantic priming paradigms. We used a different paradigm to investigate the
      relationship between depression and spreading activation, one based on word
      frequencies. Our sample included 97 undergraduates who completed the BDI-II and
      the Controlled Oral Word Association test as well as the Animal Naming test. The
      results indicated that the group scoring within the depressed ranged evidenced
      greater spreading activation as compared to those who scored within the normal
      range on the BDI-II. The implications of these results as they relate to
      creativity in depression is discussed.

PMID- 21889249
TI  - The extent of working memory deficits associated with Williams syndrome:
      exploration of verbal and spatial domains and executively controlled processes.
AB  - The present study investigated verbal and spatial working memory (WM) functioning
      in individuals with the neuro-developmental disorder Williams syndrome (WS) using
      WM component tasks. While there is strong evidence of WM impairments in WS,
      previous research has focused on short-term memory and has neglected assessment
      of executive components of WM. There is a particular lack of consensus concerning
      the profile of verbal WM functioning in WS. Here, WS participants were compared
      to typically developing participants matched for (1) verbal ability and (2)
      spatial ability (N=14 in each of the 3 groups). Individuals with WS were impaired
      on verbal WM tasks, both those involving short-term maintenance of information
      and executive manipulation, in comparison to verbal-matched controls.
      Surprisingly, individuals with WS were not impaired on a spatial task assessing
      short-term maintenance of information in memory (remembering spatial locations)
      compared to spatial-matched controls. They were, however, impaired on a spatial
      executive WM task requiring the manipulation of spatial information in memory.
      The present study suggests that individuals with WS show WM impairments that
      extend to both verbal and spatial domains, although spatial deficits are
      selective to executive aspects of WM function.

PMID- 21889250
TI  - Transfer of short-term motor learning across the lower limbs as a function of
      task conception and practice order.
AB  - Interlimb transfer of motor learning, indicating an improvement in performance
      with one limb following training with the other, often occurs asymmetrically
      (i.e., from non-dominant to dominant limb or vice versa, but not both). In the
      present study, we examined whether interlimb transfer of the same motor task
      could occur asymmetrically and in opposite directions (i.e., from right to left
      leg vs. left to right leg) depending on individuals' conception of the task. Two
      experimental conditions were tested: In a dynamic control condition, the process
      of learning was facilitated by providing the subjects with a type of information
      that forced them to focus on dynamic features of a given task (force impulse);
      and in a spatial control condition, it was done with another type of information
      that forced them to focus on visuomotor features of the same task (distance).
      Both conditions employed the same leg extension task. In addition, a fully
      crossed transfer paradigm was used in which one group of subjects initially
      practiced with the right leg and were tested with the left leg for a transfer
      test, while the other group used the two legs in the opposite order. The results
      showed that the direction of interlimb transfer varied depending on the
      condition, such that the right and the left leg benefited from initial training
      with the opposite leg only in the spatial and the dynamic condition,
      respectively. Our finding suggests that manipulating the conception of a leg
      extension task has a substantial influence on the pattern of interlimb transfer
      in such a way that the direction of transfer can even be opposite depending on
      whether the task is conceived as a dynamic or spatial control task.

PMID- 21889251
TI  - Biological markers of cognition in prodromal Huntington's disease: a review.
AB  - Huntington's disease (HD), an autosomal-dominant genetic disorder, has
      historically been viewed as a degenerative movement disorder but it also includes
      psychiatric symptoms and progressive cognitive decline. There has been a lack of
      consensus in the literature about whether or not cognitive signs can be detected
      in carriers before clinical (motor) onset of the disease, i.e., prodromal HD.
      However, recently validated mathematical formulas to estimate age of clinical
      onset, refined over the past 5-7 years, have allowed researchers to overcome the
      methodological limitation of treating all prodromal carriers as a homogenous high
      risk group (i.e., whether they may be 2 or 15 years from diagnosis). Here we
      review 23 articles on the HD prodrome, all of which related cognition to a
      biological marker of disease burden (i.e., genetic load, neuroimaging). All
      studies found at least one cognitive domain was associated with disease burden in
      prodromal HD participants. There was greater variability in both the detection
      and cognitive domain affected in those farther from onset (or those with less
      pathology) while most studies reliably found declines in visuomotor performance
      and working memory in those closer to onset. These findings indicate that
      cognitive signs can be reliably detected in the HD prodrome when comparing
      cognition to additional disease markers, however, there continues to be
      significant variability on cognitive findings among large and methodologically
      rigorous studies. This may reflect true heterogeneity in the prodromal HD
      phenotype which must be further explored by analyzing intra-individual variance,
      determining demographic risk factors associated with decline/protection, and
      examining if particular HD families exhibit distinct cognitive profiles. These
      and additional future directions are discussed.

PMID- 21889252
TI  - [Sequelae of burns of the breast and their reconstruction].
AB  - Sequelae of burns on the breast are essentially cosmetic. Requests for their
      reconstruction take place after the request for the face and hands. The problems
      is to face the consequences by considering the growth of mammary gland either
      hormonal in case of children or breast reconstruction as if in case of malgnancy
      in adult female. We propose a classification, which is helpful to choose the
      surgical treatment. Our technique of choice is tissue expansion (local or
      regional cutaneous flaps or full skin graft).

PMID- 21889253
TI  - [Psychiatric and behavioral aspects of cardiovascular disease: epidemiology,
      mechanisms, and treatment].
AB  - Psychosocial and behavioral factors, including mood (depression, anxiety, anger,
      and stress), personality (Type A, Type D, and hostility), and social support, are
      associated with both the development and progression of cardiovascular disease.
      "Negative" emotions have been associated with increased rates of cardiovascular
      death and recurrent cardiac events, although the mechanisms responsible for this
      association remain unclear. A number of pathophysiological mechanisms have been
      proposed to explain these relationships, including hypothalamic-pituitary-adrenal
      axis dysregulation, platelet activation, and inflammation. Behavioral factors
      also have been implicated, such as nonadherence to prescribed medical therapies
      and physical inactivity. Several randomized trials of patients with
      cardiovascular disease have examined the impact of pharmacologic and behavioral
      treatments on hard cardiovascular disease events as well as on cardiovascular
      disease biomarkers of risk. Although psychological treatments generally have been
      shown to improve quality of life and psychological functioning among cardiac
      patients, the benefit of psychological interventions with respect to improving
      clinical outcomes has not been conclusively demonstrated.

PMID- 21889255
TI  - Potential correlation of intrathecal baclofen concentration and clinical
      improvement after high dose intrathecal intoxication: a case report.

PMID- 21889254
TI  - Prevalence of aspirin-exacerbated respiratory disease in patients with asthma in
      Turkey: a cross-sectional survey.
AB  - BACKGROUND: There are no country-based data focused on aspirin (ASA)-exacerbated
      respiratory disease (AERD) in Turkey. OBJECTIVE: To assess the prevalence of AERD
      in adult patients with asthma. METHODS: A structured questionnaire was
      administered via face-to-face interview by a specialist in pulmonology/allergy at
      seven centres across Turkey. RESULTS: A total of 1344 asthma patients (F/M:
      1081/263: 80.5%/19.5%, mean age: 45.7 +/- 14.2 years) were enrolled. Atopy rate
      was 47%. Prevalence of allergic rhinitis, chronic rhinosinusitis/rhinitis, and
      nasal polyposis (NP) were 49%, 69% and 20%, respectively. Of 270 patients with
      NP, 171 (63.3%) reported previous nasal polypectomy and 40 (25%) had a history of
      more than three nasal polypectomies. Aspirin hypersensitivity was diagnosed in
      180 (13.6%) asthmatic patients, with a reliable history in 145 (80.5%), and oral
      ASA provocation test in 35 (19.5%) patients. Clinical presentations of ASA
      hypersensitivity were respiratory in 76% (n=137), respiratory/cutaneous in 15%
      (n=27), and systemic in 9% (n=16) of the patients. Multivariate analysis
      indicated that a family history of ASA hypersensitivity (p: 0.001, OR: 3.746, 95%
      CI: 1.769-7.929), history of chronic rhinosinusitis/rhinitis (p: 0.025, OR:
      1.713, 95% CI: 1.069-2.746) and presence of NP (p<0.001, OR: 7.036, 95% CI: 4.831
      10.247) were independent predictors for AERD. CONCLUSION: This cross-sectional
      survey showed that AERD is highly prevalent among adult asthmatics and its
      prevalence seems to be affected by family history of ASA hypersensitivity,
      history of rhinosinusitis and presence of NP.

PMID- 21889256
TI  - Early prognostic factors related to progression and malignant transformation of
      low-grade gliomas.
AB  - OBJECTIVE: Low-grade gliomas (LGGs) are infiltrative tumors characterized by slow
      growth. However, during early period, LGGs can progress and transform into a
      malignant pathology. We analyzed the prognostic factors for progression and
      malignant transformation in LGGs. MATERIALS AND METHODS: From 2000 to 2009, we
      operated on 86 patients: 42 oligodendrogliomas, 12 oligoastrocytomas, and 32
      astrocytomas. The male:female ratio was 47:39, and the median age was 41 (+/
      17.4) years. The mean follow-up period was 4.25 (+/-2.8) years. We analyzed the
      prognostic factors for progression-free survival (PFS), overall survival (OS),
      and malignant transformation, considering age, sex, KPS, clinical presentation,
      tumor location, radiologic pattern, extent of removal, pathologic subtype, and
      adjuvant treatment. RESULTS: In univariate analysis, non-eloquent location, gross
      total removal, and oligodendroglial pathology statistically correlated with
      improved PFS and OS. In multivariate analysis, gross total removal correlated
      with longer PFS (p=0.043), and gemistocytic astrocytoma had a poor PFS (p=0.004).
      Younger age and non-eloquent area showed an improved OS (p=0.002 and 0.041), and
      astrocytic pathology showed a poor OS (p=0.01). Malignant transformation was
      pathologically diagnosed in 13 out of 86 patients (15%). Gemistocytic astrocytoma
      correlated independently with malignant transformation (p=0.022). CONCLUSION: In
      LGGs, extent of removal associated with tumor progression. The pathology of
      astrocytoma, especially gemistocytic astrocytoma, was an independent prognostic
      factor for recurrence and malignant transformation.

PMID- 21889258
TI  - Hemorrhagic leukoencephalitis accompanied by Epstein-Barr virus.

PMID- 21889257
TI  - The successful long-term management of an intracranial inflammatory
      myofibroblastic tumor with corticosteroids.

PMID- 21889259
TI  - A review on techniques to enhance electrochemical remediation of contaminated
      soils.
AB  - Electrochemical remediation is a promising remediation technology for soils
      contaminated with inorganic, organic, and mixed contaminants. A direct-current
      electric field is imposed on the contaminated soil to extract the contaminants by
      the combined mechanisms of electroosmosis, electromigration, and/or
      electrophoresis. The technology is particularly effective in fine-grained soils
      of low hydraulic conductivity and large specific surface area. However, the
      effectiveness of the technology may be diminished by sorption of contaminants on
      soil particle surfaces and various effects induced by the hydrogen ions and
      hydroxide ions generated at the electrodes. Various enhancement techniques have
      been developed to tackle these diminishing effects. A comprehensive review of
      these techniques is given in this paper with a view to providing useful
      information to researchers and practitioners in this field.

PMID- 21889260
TI  - Stabilization of ZnCl2-containing wastes using calcium sulfoaluminate cement:
      cement hydration, strength development and volume stability.
AB  - The potential of calcium sulfoaluminate (CSA) cement was investigated to solidify
      and stabilize wastes containing large amounts of soluble zinc chloride (a strong
      inhibitor of Portland cement hydration). Hydration of pastes and mortars prepared
      with a 0.5 mol/L ZnCl(2) mixing solution was characterized over one year as a
      function of the gypsum content of the binder and the thermal history of the
      material. Blending the CSA clinker with 20% gypsum enabled its rapid hydration,
      with only very small delay compared with a reference prepared with pure water. It
      also improved the compressive strength of the hardened material and significantly
      reduced its expansion under wet curing. Moreover, the hydrates assemblage was
      less affected by a thermal treatment at early age simulating the temperature rise
      and fall occurring in a large-volume drum of cemented waste. Fully hydrated
      materials contained ettringite, amorphous aluminum hydroxide, stratlingite,
      together with AFm phases (Kuzel's salt associated with monosulfoaluminate or
      Friedel's salt depending on the gypsum content of the binder), and possibly C-(A)
      S-H. Zinc was readily insolubilized and could not be detected in the pore
      solution extracted from cement pastes.

PMID- 21889261
TI  - The paradox of pain from tooth pulp: low-threshold "algoneurons"?

PMID- 21889262
TI  - Chronic postsurgical pain after nitrous oxide anesthesia.
AB  - Nitrous oxide is an antagonist at the N-methyl-D-aspartate receptor and may
      prevent the development of chronic postsurgical pain. We conducted a follow-up
      study in the Evaluation of Nitrous Oxide in the Gas Mixture for Anaesthesia
      (ENIGMA) trial patients to evaluate the preventive analgesic efficacy of nitrous
      oxide after major surgery. The ENIGMA trial was a randomized controlled trial of
      nitrous oxide-based or nitrous oxide-free general anesthesia in patients
      presenting for noncardiac surgery lasting more than 2 hours. Using a structured
      telephone interview, we contacted all ENIGMA trial patients recruited in Hong
      Kong (n=640). We recorded the severity of postsurgical pain of at least 3 months'
      duration that was not due to disease recurrence or a pre-existing pain syndrome,
      using the modified Brief Pain Inventory. The impact of postsurgical pain on
      quality of life was also measured. Pain intensity, opioid and other analgesic
      requirements during the first week of surgery, were retrieved from the trial case
      report form and medical records. A total of 46 (10.9%) patients reported pain
      that persisted from the index surgery, and 39 (9.2%) patients had severe pain. In
      addition, patients with chronic pain rated poorly in all attributes of the
      quality-of-life measures compared with those who were pain free. In a
      multivariate analysis, nitrous oxide decreased the risk of chronic postsurgical
      pain. In addition, severe pain in the first postoperative week, wound
      complication, and abdominal incision increased the risk of chronic pain. In
      conclusion, chronic postsurgical pain was common after major surgery in the
      ENIGMA trial. Intraoperative nitrous oxide administration was associated with a
      reduced risk of chronic postsurgical pain.

PMID- 21889263
TI  - Associations between depression, pain behaviors, and partner responses to pain in
      metastatic breast cancer.
AB  - Women with metastatic breast cancer (MBC) rely on their partners for emotional
      and practical support. They also experience significant pain and depression,
      which can trigger maladaptive pain behaviors (eg, distorted ambulation). The
      biopsychosocial model of pain posits that partner solicitous responses can
      reinforce pain behaviors, whereas punishing or distracting responses can minimize
      their occurrence. This study explored how psychosocial variables (ie, depression
      and partner responses) influence patient pain behaviors and partner responses in
      191 couples coping with MBC. Because few studies have examined the
      biopsychosocial model in cancer, it also examined associations between partner
      responses and patient pain behaviors. Multilevel models showed that depression
      partially mediated: (1) associations between patients' and partners' reports of
      patient pain (MPI) and their ratings of patient pain behaviors (PBCL), accounting
      for 41% to 71% of the variance; and (2) associations between both partners'
      reports of patient pain and the partner's distracting and punishing responses
      (MPI), accounting for 66% to 75% of the variance. Partner punishing responses
      moderated associations between patient pain severity and pain behaviors.
      Specifically, punishing responses were associated with more pain behaviors for
      patients with low levels of pain and fewer pain behaviors for patients with
      higher levels of pain (effect size r=.18). These findings provide partial support
      for the biopsychosocial model of pain but also clarify and extend it in the
      cancer context. Future pain management programs in MBC may benefit from
      addressing both partners' depression levels and teaching partners to engage in
      fewer punishing responses when the patient is experiencing low levels of pain.

PMID- 21889264
TI  - Theileria parva, T. sp. (buffalo) and T. sp. (bougasvlei) 18S variants.

PMID- 21889265
TI  - Management and environmental factors related to benzimidazole resistance in sheep
      nematodes in Northeast Spain.
AB  - A survey to determine the level of parasite resistance to benzimidazoles (BZ)
      under field conditions was performed on 107 commercial sheep farms located in the
      Aragon region of northeast Spain. Resistance was measured using the discriminant
      dose, a simplified form of the in vitro egg hatch assay (EHA). Taking into
      account the spatial structure of the data, a multivariate approach was applied to
      management and environmental variables as well as to their relationships with BZ
      resistance levels compiled from each flock. Results estimated that 11% of flocks
      had resistant parasite populations, although we suspected the presence of BZ
      resistant parasite strains in 98% of the sample. Resistance levels were more
      similar among the nearest flocks, suggesting a contagious spatial distribution of
      resistance (i.e., resistance at neighbouring farms was not independent from one
      another). Management variables such as frequency of deworming, grazing in private
      pastures and underdosing were positively related to resistance levels, whereas
      only the use of BZ was negatively related to resistance levels, likely because BZ
      were replaced by other anthelmintics in flocks where reduced BZ efficacy was
      suspected. In addition to climatic conditions and seasonality, land use was an
      environmental variable associated with observed BZ resistance levels. Generally,
      resistance was highest in cooler and wetter areas but was lower in flocks sampled
      during January-March compared to flocks sampled in April-June or October
      December. Variation partitioning procedures showed that the variation of
      resistance explained by the effect of environmental variables was higher than
      management variables. The effects of both variable groups, however, highly
      overlapped with the spatial structure of resistant levels, which suggests that a
      considerable amount of the effects attributable to both variable groups may be
      actually due to the spatial distribution of resistance. The resistance variation
      explained by the spatial component suggested that other uncontrolled factors
      acting at short spatial scale (e.g., common management and environmental
      variables; the importation of resistant strains and their posterior spread across
      neighbouring flocks; the selection history of the worms carried out by historical
      management events previous to this survey; and genetic, physiological or both
      types of parasite population variation) could yield this contagious spatial
      structure of BZ resistance. Although further research is needed, both seasonal
      variation and the dependence of resistance levels among neighbouring flocks
      should be taken into account in the design of future research or observational
      resistance programmes to minimise spatial and temporal pseudo-replication. Thus,
      research would avoid biased estimations of resistance prevalence or of its
      relationship with putative factors.

PMID- 21889266
TI  - National monitoring of Ascaris suum related liver pathologies in English
      abattoirs: a time-series analysis, 2005-2010.
AB  - Ascaris suum is the most important internal parasite in farmed pigs world-wide.
      In England, the BPEX Pig Health Scheme (BPHS) monitors the prevalence of
      ascariosis in slaughtered finished pigs by identifying milk spots - the healing
      lesions caused by A. suum larvae migration through the liver. This study
      investigates the trend of milk spot lesions from July 2005 to December 2010 to
      identify the progress made by the industry in controlling this parasitic disease.
      For visual explorations, the monthly prevalence for milk spots was modelled using
      "STL", a seasonal-trend decomposition method based on locally weighted
      regression. Random effects binomial modelling accounting for clustering at batch
      level was used to test the significance of the trend and seasonality.
      Additionally, the differences in the milk spot prevalence trends for BPHS members
      (those that joined the scheme) and non-members were investigated and tested. A
      mean of 12,442 pigs was assessed per month (in 290 batches) across 12 pig
      abattoirs over the study period, from which a monthly mean of 7102 pigs (159
      batches) came from BPHS members. A mild overall decrease in prevalence of milk
      spots over the monitored period was identified as well as a seasonal variation
      which showed peaks in summer and at the beginning of autumn. BPHS members
      maintained a lower prevalence than non-members. The results from this work
      illustrate ascariosis as a persistent problem in current farm production.

PMID- 21889268
TI  - Potential role of reactive metabolites of addictive drugs at the receptor: a
      novel hypothesis.
AB  - The central nervous system (CNS) stimulants to CNS depressants such as morphine,
      cocaine, methamphetamine and nicotine each have the capacity for inducing
      chemical dependence with an enormous impact on human behavior. Because of the
      difficulties in isolation, the role of the reactive metabolites as a modulating
      factor in the receptor activation and related addiction of these drugs is not
      studied. The chemical transformations of these compounds to their metabolites at
      the receptors have been proposed. There is the distinct possibility that
      irreversible binding of N-hydroxy, N-formyl or related metabolites of morphine,
      cocaine, methamphetamine, or nicotine with the respective receptors can occur.
      This unique role of highly reactive molecular species is postulated. In this way,
      the synaptic glutaminergic and or dopaminergic transmission can be compromised.
      On repeated exposure of the drug, the receptor reserve may decrease. More drug is
      needed to activate the residual receptor to maintain the reward in addiction.

PMID- 21889267
TI  - The psychosocial, endocrine and immune consequences of caring for a child with
      autism or ADHD.
AB  - Research that has assessed the psychophysiological consequences of caregiver
      stress in young and middle aged caregivers, that is, in populations not
      contending with age associated decline of the endocrine and immune systems, has
      been scarce and yielded inconsistent findings. To extend work in this area, this
      study assessed the psychosocial, endocrine and immune consequences of caregiver
      stress in a cross sectional sample of young and middle aged caregivers of
      children with autism and attention deficit hyperactivity disorder (ADHD) compared
      against parents of typically developing children. Caregivers (n=56) and parent
      controls (n=22) completed measures of psychological distress (perceived stress,
      anxiety/depression), social support and physical health complaints. To capture
      important indices of the diurnal cortisol pattern, cortisol was measured at
      waking, 30 min post waking, 1200 h and 2200 h on two consecutive weekdays. Venous
      blood was taken to assess systemic concentrations of proinflammatory biomarkers,
      interleukin-6 (IL-6) and C-reactive protein (CRP). Caregivers scored markedly
      higher on all measures of psychological distress; scores on social support
      subscales, however, were significantly lower in this group. Diurnal patterns of
      cortisol secretion did not differentiate between the groups; however, caregivers
      displayed elevated systemic concentrations of the proinflammatory biomarker, CRP
      and reported more frequent episodes of physical ill health. The stress of
      caregiving exacts a significant psychophysiological toll, that is, even in the
      absence of HPA dysregulation, caregivers demonstrated elevated concentrations of
      proinflammatory biomarkers and, therefore, might be at greater risk for diseases
      fostered by disinhibition of the inflammatory response.

PMID- 21889269
TI  - Myosin light chain 1 release from myofibrillar fraction during postmortem aging
      is a potential indicator of proteolysis and tenderness of beef.
AB  - The objective of this study was to identify proteins in bovine longissimus dorsi
      muscle that are related to tenderness. Two dimensional difference in gel
      electrophoresis (2D-DIGE) was used to compare the sarcoplasmic fractions from
      steaks that differed in star probe values at 14 days postmortem. The intensity of
      myosin light chain 1 (MLC1) was greater in the sarcoplasmic fraction prepared
      from steaks that had lower star probe values. It was hypothesized that MU-calpain
      catalyzes the release MLC1 into the sarcoplasmic fraction. Myofibrils from beef
      longissimus dorsi were purified and incubated with MU-calpain and the appropriate
      buffer controls. MU-Calpain was added at 1.23 MUg (0.0875 U) of pure MU
      calpain/mg myofibrillar protein. Incubations of one and 120 min had a greater
      abundance of MLC1 in the supernatants than the control incubations. As a
      consequence of MU-calpain proteolysis, MLC1 is rapidly released from the
      myofibril and is a potential indicator of proteolysis and improvement in beef
      tenderness.

PMID- 21889270
TI  - Profile of NF-kappaBp(65/NFkappaBp50) among prostate specific antigen sera levels
      in prostatic pathologies.
AB  - AIM: The aim of this work was to characterise the immunoexpression of NF-kappaB
      (p50/p65) in human prostatic pathologies and to study its profiles of activation
      among sera prostate specific antigen antigen (PSA) according the three groups: 0
      4ng/mL, 4-20ng/mL and >20ng/mL. PATIENTS AND METHODS: Twenty-four men with benign
      prostate hyperplasia (BPH); 19 men with prostate cancer (PC) and five men with
      normal prostates (NP). Immunohistochemical and western blot analysis was
      performed. Serum levels of PSA were assayed by immulite autoanalyser. RESULTS: In
      BPH and PC samples, immunoexpressions were observed for NF-kappaBp65 and NF
      kappaBp50; while in NP samples, only were detected NF-kappaBp50. PC samples
      showed immunoreactions to NF-kappaBp65 and NF-kappaBp50 more intense
      (respectively 24.18+/-0.67 and 28.23+/-2.01) than that observed in BPH samples
      (respectively18.46+/-2.04 and 18.66+/-1.59) with special localisation in the
      nucleus. Different profiles of NF-kappaBp65 immunoexpressions were observed and
      BPH patients with sera PSA levels between 0-4ng/mL presented a significant weak
      percentage compared to BPH patients with sera PSA levels between 4-20ng/mL and
      >20ng/mL. No immunoreactions to NF-kappaBp65 were observed in PC patients with
      sera PSA levels between 4-20ng/mL. CONCLUSION: The sensibility of both NF-kappaB
      and PSA to inflammation allowed confirming the relationship between these two
      molecules and its involvement in prostatic diseases progression (inflammatory and
      neoplasic).

PMID- 21889271
TI  - Intra-species diversity and epidemiology varies among coagulase-negative
      Staphylococcus species causing bovine intramammary infections.
AB  - Although many studies report coagulase-negative staphylococci (CNS) as the
      predominant cause of subclinical bovine mastitis, their epidemiology is poorly
      understood. In the current study, the genetic diversity within four CNS species
      frequently associated with bovine intramammary infections, Staphylococcus
      haemolyticus, S. simulans, S. chromogenes, and S. epidermidis, was determined.
      For epidemiological purposes, CNS genotypes recovered from bovine milk collected
      on six Flemish dairy farms were compared with those from the farm environment,
      and their distribution within the farms was investigated. Genetic diversity was
      assessed by two molecular typing techniques, amplification fragment length
      polymorphism (AFLP) and random amplification of polymorphic DNA (RAPD) analysis.
      Subtyping revealed the highest genetic heterogeneity among S. haemolyticus
      isolates. A large variety of genotypes was found among environmental isolates, of
      which several could be linked with intramammary infection, indicating that the
      environment could act as a potential source for infection. For S. simulans,
      various genotypes were found in the environment, but a link with IMI was less
      obvious. For S. epidermidis and S. chromogenes, genetic heterogeneity was limited
      and the sporadic isolates from environment displayed largely the same genotypes
      as those from milk. The higher clonality of the S. epidermidis and S. chromogenes
      isolates from milk suggests that specific genotypes probably disseminate within
      herds and are more udder-adapted. Environmental sources and cow-to-cow
      transmission both seem to be involved in the epidemiology of CNS, although their
      relative importance might substantially vary between species.

PMID- 21889272
TI  - The differences in testicular volumes in boys 8-36 months old with undescended,
      retractile and hydrocele testis--usefulness of scrotal screening ultrasound.
AB  - PURPOSE: The aim of the study was quantitative and qualitative assessments of
      scrotal abnormalities diagnosed in boys 8 to 36 months old during ultrasound
      screening and estimation if these abnormalities influence testes volume.
      MATERIALS AND METHODS: High frequency scrotal ultrasound was performed in 1448
      patients aged 8-36 months as additional exam during screening ultrasound program
      for children including cervical and abdominal ultrasound. The mean age of
      examined boys was 17 months. For further analysis the children were divided in 5
      age groups. RESULTS: The abnormalities in scrotal ultrasound were found in 20.1%
      of boys. Undescended, cryptorchid testes were found in 4.8% of patients, mobile
      testicle in 7.6% and hydrocele in 2.8%. The volume of undescended testes was
      statistically lower than volume of the descended testes in 3 youngest groups of
      boys (p=0.003-0.011). The volume of mobile testicles did not increase with age,
      while in patients with hydrocele the testicular volume decreased with age.
      CONCLUSION: Scrotal screening ultrasound performed in boys up to 3 years old may
      deliver information about the number and type of existing pathologies as well as
      their influence on the testicular volume. The volume of the pathological testes
      was lower than the volume of the normal ones. Improper growth of testes may
      potentially have important clinical implication for the function of testes in the
      future.

PMID- 21889273
TI  - Histomorphometric evaluation of the neotropical brown brocket deer Mazama
      gouazoubira testis, with an emphasis on cell population indexes of spermatogenic
      yield.
AB  - Information on the reproductive biology of neotropical cervids is scarce.
      Therefore, the aim of this study was to perform biometric, histologic and
      stereologic analyses of the brown brocket deer Mazama gouazoubira testis, with an
      emphasis on the intrinsic yield and the Sertoli cell index. Seven adult males
      kept in captivity were used. The animals were immobilized; anesthetized and
      testicle fragments were obtained by biopsy incision. The material was fixed,
      processed and examined by routine histological methods for light microscopy. The
      average body weight was 17.2kg, from which 0.40% were allocated in gonads and
      0.33% in seminiferous tubules, which represented 85.9% of the testis parenchyma.
      The mean albuginea width and volume were 345.7MUm and 3.5mL (5.3% of the
      testicular weight), respectively. The mean mediastinum volume of both testicles
      was 1.0mL (1.5% of the testicular weight) and the testicular parenchyma volume
      corresponded to 93.1% of total testicular weight (64.9g). The seminiferous
      tubules diameter was 224.4MUm, while the epithelium height was 69.6MUm. On
      average, an adult brown brocket deer showed a total of 1418m of seminiferous
      tubules in both testicles (21.5m per gram of testis). Each stage I seminiferous
      tubular cross section contained 1.10 type A spermatogonia, 13.4 primary
      spermatocytes in pre-leptotene/leptotene, 13.7 spermatocytes in pachytene, 48.8
      round spermatids and 3.7 Sertoli cells. The general yield of spermatogenesis was
      44.7 cells and the Sertoli cell index was 13.2. The qualitative and quantitative
      description of testicular histology of brown brocket deer help to understand its
      spermatogenic process and to establish parameters for the reproductive biology of
      this wild species. Furthermore, the data from the present research will help
      further studies using other species of Brazilian cervids, especially endangered
      ones, making an additional effort to the species preservation.

PMID- 21889274
TI  - Current strategic approaches for the detection of blood doping practices.
AB  - Aerobic sport performance may be strongly influenced by the number of red blood
      cells available for transport and delivery of oxygen from lungs to muscles.
      Often, athletes search for an acute increase in red blood cells by means of blood
      transfusions. This paper reviews the possibilities for detecting such prohibited
      practice. Flow cytometry methods are able to detect a double population of red
      blood cell membrane surface antigens, thus revealing an allogeneic transfusion.
      Other ingenious approaches for total hemoglobin mass measurements or to test for
      the metabolites of blood bag plasticizers in urine are new trends for facing the
      detection of autologous transfusions. Steady increase of red blood cell number
      may be obtained also by erythropoietic stimulant agents such as erythropoietin,
      analogs and mimetics. The challenge of detecting those substances has stimulated
      the development of indirect markers of altered erythropoiesis, leading to the
      consequent development of the hematological blood passport approach, which is
      gaining legal acceptance.

PMID- 21889275
TI  - Microcrystalline identification of selected designer drugs.
AB  - A microcrystalline test for the detection of 4-methylmethcathinone (mephedrone),
      benzylpiperazine (BZP) and 5,6-methylenedioxy-2-aminoindane (MDAI) using aqueous
      solutions of mercury chloride is described. Each of the compounds investigated
      formed specific drug-reagent crystals within minutes. The uniqueness of the test
      was confirmed by comparison of the microcrystalline response to that of other
      psychoactive stimulants and a common cutting agent. The limit of detection and
      cut-off levels for reference standards were established to 3 g/L and 5 g/L for
      mephedrone, 0.5 g/L for MDAI and 0.2 g/L and 0.3 g/L for BZP, respectively.
      Various mixtures of standards of either mephedrone, BZP or MDAI combined with
      caffeine were investigated for their microcrystalline response. Results showed
      that simultaneous detection of drug and cutting agent was possible with the
      concentrations tested but were dependant on the ratio of drug to cutting agent.
      BZP could be detected alongside caffeine from as low as 20% (v/v), MDAI from 40%
      (v/v) and mephedrone from 50% (v/v) and higher. Finally, seven samples of online
      purchased 'legal highs' were analysed using the developed test and the findings
      were compared to FTIR and GC-MS results. It was shown that 6 out of 7 samples did
      not contain the advertised active ingredient. Five samples consisted of BZP,
      caffeine and 1-[3-(trifluoromethyl)phenyl]piperazine (3-TFMPP). The
      microcrystalline tests carried out on these samples showed positive results for
      both BZP and caffeine without interference from other substances present.

PMID- 21889276
TI  - Fluorescence flow cytometer to determine urine particle reference intervals in
      doping control samples.
AB  - BACKGROUND: Urine is still the matrix of choice to fight against doping, because
      it can be collected non-invasively during anti-doping tests. Most of the World
      Anti-Doping Agency's accredited laboratories have more than 20 years experience
      in analyzing this biological fluid and the majority of the compounds listed in
      the 2010 Prohibited List-International Standard are eliminated through the
      urinary apparatus. Storing and transporting urine samples for doping analyses
      does not include a specific protocol to prevent microbial and thermal
      degradation. The use of a rapid and reliable screening method could enable
      determine reference intervals for urine specimens in doping control samples and
      evaluate notably the prevalence of microbial contamination known to be
      responsible for the degradation of chemical substances in urine. METHODS: The
      Sysmex(r) UF-500i is a recent urine flow cytometer analyzer capable of
      quantifying BACT and other urinary particles such as RBC, WBC, EC, DEBRIS, CAST,
      PATH.CAST, YLC, SRC as well as measuring urine conductivity. To determine urine
      anti-doping reference intervals, 501 samples received in our laboratory over a
      period of two months were submitted to an immediate examination. All samples were
      collected and then transported at room temperature. Analysis of variance was
      performed to test the effects of factors such as gender, test type [in
      competition, out-of-competition] and delivery time. RESULTS: The data obtained
      showed that most of the urine samples were highly contaminated with bacteria. The
      other urine particles were also very different according to the factors.
      CONCLUSIONS: The Sysmex(r) UF-500i was capable of providing a snapshot of urine
      particles present in the samples at the time of the delivery to the laboratory.
      These particles, BACT in particular, gave a good idea of the possible microbial
      degradation which had and/or could have occurred in the sample. This information
      could be used as the first quality control set up in WADA (World Anti-Doping
      Agency) accredited laboratories to determine if steroid profiles, endogenous and
      prohibited substances have possibly been altered.

PMID- 21889277
TI  - How to confirm C.E.R.A. doping in athletes' blood?
AB  - C.E.R.A. (Continuous Erythropoietin Receptor Activator) is a new third-generation
      erythropoiesis-stimulating agent that has recently been linked with abuse in
      endurance sports. The anti-doping community rapidly reacted by releasing a high
      throughput screening ELISA allowing the detection of C.E.R.A. doping in athletes'
      blood. In order to return adverse analytical findings, anti-doping laboratories,
      however, need, as far as possible, to confirm the presence of the drug in
      athletes' samples through orthogonal methods. This article focuses on the
      comparison of 2 proposed confirmation assays based on gel electrophoresis that
      were coupled with a new sample immunopurification method. IEF, the classical
      method used to target erythropoietin (EPO) and its recombinant analogues in
      athletes' samples, and SARKOSYL-PAGE were applied to the plasma samples of
      subjects having received a single injection of C.E.R.A. It was demonstrated that
      SARKOSYL-PAGE was at least 6 times more sensitive than IEF, with comparable
      specificity. A longer detection window coupled with easier interpretation
      criteria led us to recommend the use of SARKOSYL-PAGE to confirm C.E.R.A.
      presence in athletes' blood.

PMID- 21889278
TI  - Surgical management of tongue cancer during pregnancy.
AB  - There are ethical dilemmas in managing head and neck cancers during pregnancy.
      Diagnostic and treatment modalities need to be carefully determined. We herein
      describe 3 cases of tongue cancer during pregnancy. The details of the management
      would contribute to the daily practices for head and neck cancers. All three
      patients were Japanese female patients, two of them were 29 years old and one was
      26 years old. All patients were admitted to the Nippon Medical School Hospital
      during pregnancy, complaining of oral pain and/or discomfort. Case 1 was
      diagnosed as tongue cancer stage T3N0M0, however, the tumor was superficial and
      controllable by partial glossectomy. Case 2 was stage T2N0M0 with deep invasion
      with ulcer, and the hemi-glossectomy with neck dissection and the reconstruction
      was thought to be the standard modality. However, she underwent partial
      glossectomy in order to reduce the stress of the fetus. Case 3 could not be
      diagnosed on admission by biopsy and she underwent partial glossectomy after
      delivery. In case 3, the pathological diagnosis was pT1 tongue cancer. In case 1
      and case 3, the patient and baby were healthy. In case 2, however, the patient
      died of recurrence at the primary site. In decision making of the strategy, the
      most important factors are not only oncological evaluation but also ethical and
      emotional factors.

PMID- 21889279
TI  - Reversing the polarity of a cochlear implant magnet after magnetic resonance
      imaging.
AB  - The number of patients with cochlear implant (CI) has been rapidly increasing in
      recent years, and these patients show a growing need of examination by magnetic
      resonance imaging (MRI). However, the use of MRI on patients with CI is
      restricted by the internal magnet of the CI. Many studies have investigated the
      safety of performing 1.5T MRI on patients with CI, which is now being practiced
      in a clinical setting. We experienced a case in which the polarity of the
      cochlear implant magnet was reversed after the patient was examined using 1.5T
      MRI. The external device was attached to the internal device oppositely. We could
      not find displacement of the internal device, magnet, or electrode upon
      radiological evaluation. We came up with two possible mechanisms by which the
      polarity of the magnet reversed. The first possibility was that the magnetic
      field of MRI reversed the polarity of the magnet. The second was that the
      internal magnet was physically realigned while interacting with the MRI. We
      believe the second hypothesis to be more reliable. A removable magnet and a loose
      magnet boundary of a CI device may have allowed for physical reorientation of the
      internal magnet. Therefore, in order to avoid these complications, first, the
      internal magnet must not be aligned anti-parallel with the magnetic polarity of
      MRI. In the Siemens MRI, the vector of the magnetic field is downward, so implant
      site should be placed in facing upwards to minimize demagnetization. In the GE
      Medical Systems MRI, the vector of the magnetic field is upward, so the implant
      site should be placed facing downwards. Second, wearing of a commercial mold
      which is fixed to the internal device before performing MRI can be helpful. In
      addition, any removable internal magnets in a CI device should be removed before
      MRI, especially in the trunk. However, to ultimately solve this problem, the
      pocket of the internal magnet should be redesigned for safety.

PMID- 21889280
TI  - An ectopic hamartomatous thymoma.
AB  - An ectopic hamartomatous thymoma is an extremely rare benign tumor of the lower
      neck that is the most common in middle-aged males. Pathologically, the tumor is
      characterized by a mixture of spindle cells, epithelial cells, mature adipose
      tissue, and lymphocytes. The histogenesis of this tumor is controversial.
      Recently, an origin from a remnant of the cervical sinus of His was proposed.
      Malignant lesions such as synovial sarcomas or malignant peripheral nerve sheath
      tumors can have similar clinical features and radiologic images. Thus,
      recognition of this tumor is important because it follows a benign clinical
      course and conservative surgical excision is the treatment of choice. Here, we
      report the case of a 34-year-old man with an ectopic hamartomatous thymoma in the
      left supraclavicular region and a review of the literature on this tumor.

PMID- 21889282
TI  - Amelioration of disabling myoclonus in a case of DRPLA by levetiracetam.
AB  - We report on an 18-year-old male patient with dentatorubral-pallidoluysian
      atrophy (DRPLA) (number of CAG repeats: 68) with progressive myoclonus epilepsy
      (PME), who showed a dramatic response to levetiracetam in terms of the intensity
      of myoclonus. He began to have convulsive seizures and myoclonus at 7 and 10
      years of age, respectively, and his intelligence deteriorated from 12 years of
      age. EEG showed multifocal and diffuse spike-and-wave complexes. His convulsive
      seizures were suppressed from 13 years of age. At 17 years of age, the patient
      showed gradual intensification of erratic segmental positive myoclonus as well as
      frequent atonic falls that were probably attributable to negative myoclonus. Back
      averaging of EEG data revealed cortical discharges associated with positive
      myoclonus. Photosensitive myoclonic seizures were also observed. The
      administration of levetiracetam alleviated positive myoclonus and suppressed
      atonic falls, resulting in a remarkable improvement in the patient's quality of
      daily life. Reports on the efficacy of levetiracetam for myoclonus in DRPLA are
      still rare, though its effect on PME is known in the context of other
      neurological disorders. Thus levetiracetam should be subjected to clinical trials
      as a means of disabling myoclonus in DRPLA.

PMID- 21889281
TI  - Effect of nasal mometasone furoate on the nasal and nasopharyngeal flora.
AB  - OBJECTIVE: Mometasone furoate (MF) is one of the commonly used topical steroids,
      particularly for patients with allergic rhinitis. However, its effect on the
      colonization of bacteria that may cause superinfections by suppressing the local
      immunity is not known. Thus, we investigated the effect of MF use on the nasal
      and nasopharyngeal microbial flora. MATERIALS AND METHODS: Swab samples were
      taken from 35 patients who required MF monotherapy, just before and after one
      month of the treatment. Samples were maintained in Stuart's medium. Each swab was
      transferred to 1ml of a sterile saline solution, then into the standard agar.
      After incubation under 5% carbon dioxide at 37 degrees C, colony number was
      detected per ml. RESULTS: Colony counts of nasal or nasopharyngeal microbial
      flora did not show any statistically significant alteration with one month use of
      MF. However, an increase in potential pathogens as well as normal flora bacteria
      was determined in five of the patients and six patients acquired new
      nasopharyngeal potential pathogens, mostly Moraxella catarrhalis, Pseudomonas
      aeruginosa and Staphylococcus aureus, following the use of MF. CONCLUSION: The
      use of MF for one month did not statistically significantly change the nasal and
      nasopharyngeal flora. This study indicates that MF could be increase the
      colonization of the potential pathogens in some of the patients at the
      subclinical level particularly in the nasopharyngeal area.

PMID- 21889283
TI  - Evaluation of an LC-MS/MS assay for 15N-nitrite for cellular studies of L
      arginine action.
AB  - The utility of an LC-MS/MS assay for nitrite determination in studying L-arginine
      (ARG) cellular action was examined in vitro. EA.hy926 human endothelial cells or
      cellular fractions (membrane and cytosol) were exposed to 0-500 MUM of (15)N(4)
      ARG for 2 h. (14)N-nitrite and (15)N-nitrite in the cell lysate and in the
      incubation medium were derivatized with 2,3-diaminonaphthalene (DAN) to form
      (14)N- and (15)N-naphthotriazole (i.e., (14)N-NAT and (15)N-NAT). Peak responses
      of (14)N-NAT and (15)N-NAT were analyzed by LC-MS/MS with 1H-naphth[2,3
      d]imidazole as an internal standard. The calibration curves of DAN-derivatized
      (14)N-NAT and (15)N-NAT from (14)N-nitrite and (15)N-nitrite were linear. Intra-
      and inter-day variability of the quantification was below 14.2% in quality
      control samples. Following incubation of EA.hy926 cells with (15)N(4)-ARG,
      saturable increases of (15)N-nitrite accumulation with increasing (15)N(4)-ARG
      exposure were observed clearly. This increase however could not be detected by
      the classical fluorescence method, nor were changes in (14)N-nitrite level
      observed. When cellular fractions were exposed to (15)N(4)-ARG, (15)N-nitrite
      formation was only observed in the membrane fragments. The sensitive and
      selective LC-MS/MS method reported here can be applied to quantify accumulated
      nitrite levels in human endothelial cells. The selectivity of this stable-isotope
      labeled LC-MS/MS method offers an advantage over other traditional methods for
      elucidating cellular ARG action when its stable isotope is employed as a
      substrate.

PMID- 21889284
TI  - Fluoroquinolone resistance in Escherichia coli isolated from patients attending
      Canadian hospitals is associated with the ST131 clone.

PMID- 21889285
TI  - Rational decision-making about treatment and care in dementia: a contradiction in
      terms?
AB  - OBJECTIVE: To gain caregivers' insights into the decision-making process in
      dementia patients with regard to treatment and care. METHODS: Four focus group
      interviews (n=29). RESULTS: The decision-making process consists of three
      elementary components: (1) identifying an individual's needs; (2) exploring
      options; and (3) making a choice. The most important phase is the exploration
      phase as it is crucial for the acceptance of the disease. Furthermore, the
      decision is experienced more as an emotional choice than a rational one. It is
      influenced by personal preferences whereas practical aspects do not seem to play
      a substantial role. CONCLUSION: Several aspects make decision-making in dementia
      different from decision-making in the context of other chronic diseases: (1) the
      difficulty accepting dementia; (2) the progressive nature of dementia; (3)
      patient's reliance on surrogate decision-making; and (4) strong emotions. Due to
      these aspects, the decision-making process is very time-consuming, especially the
      crucial exploration phase. PRACTICE IMPLICATIONS: A more active role is required
      of both the caregiver and the health care professional especially in the
      exploration phase, enabling easier acceptance and adjustment to the disease.
      Acceptance is an important condition for reducing anxiety and resistance to care
      that may offer significant benefits in the future.

PMID- 21889286
TI  - A historical perspective of medical terminology of aortic aneurysm.

PMID- 21889287
TI  - Thrombolysis for acute occlusion of the superior mesenteric artery.
AB  - BACKGROUND: This study evaluated the incidence, complications, and outcome of
      local intra-arterial thrombolytic therapy for acute superior mesenteric artery
      (SMA) occlusion in Sweden. METHODS: Patients undergoing local intra-arterial
      thrombolytic therapy for acute SMA occlusion were identified in the Swedish
      Vascular Registry (SWEDVASC) between 1987 and 2009. Patient data were retrieved
      in a structured protocol by local vascular surgeons at each participating
      hospital. RESULTS: Included were 34 patients (20 women) from 12 hospitals. Median
      age was 78 years. The first patient was treated in 1997, and the annual number of
      patients undergoing thrombolysis increased continuously from 2004 to 2009. Twenty
      eight patients (82%) had embolic occlusion. No patients (0%) had acute
      peritonitis, and one (3%) had bloody stools at admission. Thirty-two patients
      (94%) were diagnosed by computed tomography with intravenous contrast
      enhancement. The median dose of alteplase was 20 mg (interquartile range, 11.6
      34.0). Successful thrombolysis was achieved in 30 patients (88%). Initial
      adjunctive aspiration thromboembolectomy was performed in 10 patients. There were
      six self-limiting bleeding complications; one from the gastrointestinal tract.
      Thirteen explorative laparotomies, 10 repeat laparotomies, and eight bowel
      resections were performed. The in-hospital mortality rate was 26% (9 of 34). Age
      was not associated with in-hospital death (P = .42). Successful thrombolysis was
      associated with decreased mortality (P = .048). CONCLUSION: Local thrombolysis
      for acute SMA occlusion is a minimally invasive and effective treatment
      alternative in a select group of patients without peritonitis. The few technique
      related complications were mild.

PMID- 21889288
TI  - Proceedings of the 2010 annual meeting of the Fetal Alcohol Spectrum Disorders
      Study Group.
AB  - The annual meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG)
      was held on June 26, 2010 in San Antonio, TX, as a satellite of the Research
      Society on Alcoholism meeting. The FASDSG membership includes clinical, basic,
      and social scientists who meet to discuss recent advances and issues in Fetal
      Alcohol Spectrum Disorder (FASD) research. The central theme of the meeting was
      "Glia and Neurons: Teamwork in Pathology and Therapy." Alcohol disruption of
      neuron development and alcohol-induced neurodegeneration is central to the
      pathology and clinical expression of FASD. The active role of glia as
      perpetrator, victim, or bystander in neurotoxicology and neurodegenerative
      processes has emerged at the forefront of adult central nervous system (CNS)
      disorders and therapy. Glia- and neuron-glial interactions hold the potential to
      elucidate causes and offer treatment of FASD as well. Growing evidence indicates
      that neurons and glia are direct targets of alcohol, but may also be vulnerable
      to molecules produced in peripheral systems as a result of alcohol exposure.
      Diagnostics and therapies can take advantage of these processes and biomarkers,
      and these may be applicable to CNS pathology in FASD. Two keynote speakers,
      Howard E. Gendelman, M.D., and Ernest M. Graham, M.D, addressed the role of glia
      and neuroinflammation in brain development and neurodegeneration. The invited
      speakers and FASDSG members discussed new paradigms in CNS development and
      discuss new strategies for understanding and treating neurodegenerative disease.
      Members of the FASDSG provided updates on new findings through presentation of
      breaking research in the FASt data sessions. Representatives of national agencies
      provided updates on programs, activities, and funding priorities. The Henry
      Rosett Award was presented to R. Louise Floyd, R.N., D.S.N., for her career
      contributions to the field of fetal alcohol research. The Student and
      Postdoctoral Fellow Research Merit Award was presented to Shonagh O'Leary-Moore,
      Ph.D., for her contributions to the field as a young investigator.

PMID- 21889289
TI  - Pigmented villonodular synovitis: extrasynovial recurrence.
AB  - A 32-year-old female athlete underwent arthroscopy for a second recurrence of
      pigmented villonodular synovitis (PVNS), which was extrasynovial, seen on
      magnetic resonance imaging. It was noted on arthroscopy that (1) the nodules
      moved medially with joint insufflation, (2) the nodules were less prominent than
      on magnetic resonance imaging, and (3) more than 95% of the recurrent tumor was
      hidden by neosynovium. We believe that the extrasynovial location is because of
      the more rapid proliferation of the neosynovium relative to the growth of the
      remaining tumor cells after the previous resection. In resecting pigmented
      villonodular synovitis with a high risk of recurrence, a layer of periarticular
      fat should be removed and the surgeon should be wary of change in position with
      insufflation.

PMID- 21889290
TI  - [Slowing chronic kidney disease progression: hopes and disappointments. Vascular
      repair of chronic kidney].
AB  - In chronic kidney disease patients, inexorable renal function decline is reduced
      by renin-angiotensin system (RAS) blockers. ACE inhibitors and angiotensin
      receptor blockers decrease blood pressure and proteinuria. Guidelines recommend a
      reduction of blood pressure to less than 130/80 mmHg and urinary protein
      excretion below 0.5 g/d. The combined use of a diuretic increases anti
      proteinuric effect and blood pressure control of RAS blockers. Drugs as mineralo
      corticocoids receptor antagonist and endothelin receptor antagonists reduce
      further albuminuria in combination with RAS blocker, but side effects need to be
      precised. Both metabolic acidosis and hyperuricemia represent new therapeutic
      goals to slow renal function decline in CKD patients. Renal fibrosis treatment
      and regenerative medicine are stemming and will be important issues for kidney
      and other organs in the future.

PMID- 21889291
TI  - [Giant arachnoid cyst revealed by a spinal cord compression].

PMID- 21889292
TI  - [Cardiovascular manifestations of Marfan syndrome].

PMID- 21889293
TI  - [Cardiac failure complicating infective endocarditis due to Erysipelothrix
      rusiopathiae].

PMID- 21889294
TI  - No place like the hospital.
AB  - The gold standard for end-of-life care is home hospice. A case is presented in
      which a patient dying of irreversible small bowel obstruction from metastatic
      cancer insisted on remaining in the acute care hospital for care when alternative
      sites of care, including a skilled nursing facility and residential hospice, were
      available to her and covered by her health insurance plan. The ethical issues
      raised by this case are discussed from the perspective of the patient, the
      clinical team, the hospital, and the insurance company. Over the past decade,
      hospital-based palliative care consultation and general inpatient hospice care
      have sought to improve the quality of dying in the hospital. To the extent that
      such efforts have been successful, they may result in increasing demand for the
      hospital as the site for terminal care in the future.

PMID- 21889295
TI  - Cheek-biting disorder: another stereotypic movement disorder?
AB  - Recurrent cheek biting, a form of self-injurious behavior is a rare entity which
      presents mostly to dentists and dermatologists. We report a case of recurrent
      severe cheek biting in an adult male leading to mucosal ulceration. The
      stereotypic pattern of cheek biting and associated behavior bears striking
      resemblance to other impulse control disorders.

PMID- 21889296
TI  - Psychometric properties of the Aberrant Behavior Checklist, the Anxiety,
      Depression and Mood Scale, the Assessment of Dual Diagnosis and the Social
      Performance Survey Schedule in adults with intellectual disabilities.
AB  - Progress in clinical research and in empirically supported interventions in the
      area of psychopathology in intellectual disabilities (ID) depends on high-quality
      assessment instruments. To this end, psychometric properties of four instruments
      were examined: the Aberrant Behavior Checklist (ABC), the Assessment of Dual
      Diagnosis (ADD), the Anxiety, Depression and Mood Scale (ADAMS), and the Social
      Performance Survey Schedule (SPSS). Data were collected in two community-based
      groups of adults with mild to profound ID (n = 263). Subscale reliability
      (internal consistency) ranged from fair to excellent for the ABC, the ADAMS, and
      the SPSS (mean coefficient alpha across ABC subscales was .87 (ranging from fair
      to excellent), the ADAMS subscales .83 (ranging from fair to good), and the SPSS
      subscales .91 (range from good to excellent). The ADD subscales had generally
      lower reliability scores with a mean of .59 (ranging from unacceptable to good).
      Convergent and discriminant validity was determined by bivariate Spearman rho
      correlations between subscales of one instrument and the subscales of the other
      three instruments. For the most part, all four instruments showed solid
      convergent and discriminant validity. To examine the factorial validity,
      Confirmatory Factor Analyses (CFA) were attempted with the inter-item covariance
      matrix of each instrument. Generally, the data did not show good fits with the
      measurement models for the SPSS, ABC, or the ADAMS (CFA analyses with the ADD
      would not converge). However, most of the items on these three instruments had
      significant loadings on their respective factors.

PMID- 21889297
TI  - How do teachers with self-reported voice problems differ from their peers with
      self-reported voice health?
AB  - OBJECTIVES: This randomized case-control study compares teachers with self
      reported voice problems to age-, gender-, and school-matched colleagues with self
      reported voice health. The self-assessed voice function is related to factors
      known to influence the voice: laryngeal findings, voice quality, personality,
      psychosocial and coping aspects, searching for causative factors of voice
      problems in teachers. METHODS: Subjects and controls, recruited from a teacher
      group in an earlier questionnaire study, underwent examinations of the larynx by
      high-speed imaging and kymograms; voice recordings; voice range profile;
      audiometry; self-assessment of voice handicap and voice function; teaching and
      environmental aspects; personality; coping; burnout, and work-related issues. The
      laryngeal and voice recordings were assessed by experienced phoniatricians and
      speech pathologists. RESULTS: The subjects with self-assessed voice problems
      differed from their peers with self-assessed voice health by significantly longer
      recovery time from voice problems and scored higher on all subscales of the Voice
      Handicap Index-Throat. CONCLUSIONS: The results show that the cause of voice
      dysfunction in this group of teachers with self-reported voice problems is not
      found in the vocal apparatus or within the individual. The individual's
      perception of a voice problem seems to be based on a combination of the number of
      symptoms and of how often the symptoms occur, along with the recovery time. The
      results also underline the importance of using self-assessed reports of voice
      dysfunction.

PMID- 21889298
TI  - Determination of fundamental frequency and voice intensity in Iranian men and
      women aged between 18 and 45 years.
AB  - OBJECTIVES: Acoustic measurements have become an essential aspect of voice
      assessment during the last few decades, and studies have established that
      normative data is necessary for acoustic analysis. In this study, two aspects of
      voice are reviewed. These two factors are fundamental frequency and intensity.
      This study was designed to establish the normal acoustic analysis parameters in
      normal Iranian adults. METHODS: In this cross-sectional study, 200 healthy
      randomly selected subjects (100 men and 100 women) were assessed. Data collection
      was carried out using the Studio Speech software and Laryngograph processor
      (Laryngograph Ltd, London, UK), type: PCLX at the Larynx and Voice Disorders
      Clinic of Rasoul-e-Akram Hospital under comfortable phonation. RESULTS: The value
      of fundamental frequency in reading was greater for women (170-240 Hz) than for
      men (107-140 Hz). Also, the value of intensity was greater for women (73.54-84.99
      dB) than for men (72.40-86.03 dB). CONCLUSION: The present study developed the
      normal data for fundamental frequency and intensity in Iranian speakers aged
      between 18 and 45 years. We concluded, fundamental frequency has significant
      differences between men and women, but intensity has no significant difference
      between them.

PMID- 21889299
TI  - Acoustic measures of the voices of older singers and nonsingers.
AB  - OBJECTIVES: This study investigated whether there were differences in the
      acoustic measures of fundamental frequency (Fo), jitter, intensity, and shimmer
      of older amateur singers and nonsingers and whether there were significant
      correlations between these acoustic measurements and listener judgments of
      speaker age. METHODS: Acoustic measurements were obtained on 60 speaker
      participants from a sustained vowel production. Study participants included 30
      male and female singers and 30 male and female nonsingers between the ages of 65
      and 80 years. In addition, 10 speech-language pathology graduate students were
      recruited as listener participants to estimate the age of speaker participants
      from recorded vowel sounds. RESULTS: The results of this study indicate that
      participants were perceived as significantly younger than their real ages, and
      male and female singers were perceived to be significantly younger than male and
      female nonsingers. Significant differences were found between male and female
      singers and nonsingers regarding jitter and intensity, with singers displaying
      significantly less jitter and significantly greater intensity than nonsingers.
      Perceived age was found to be related to jitter in male singers and nonsingers
      and female singers. Perceived age was found to be related to intensity in female
      nonsingers. No statistically significant differences were found between singers
      and nonsingers regarding Fo or shimmer. No significant correlations were found
      between perceived age and intensity in male singers, male nonsingers, or female
      singers. CONCLUSIONS: Acoustic and auditory-perceptual features of the aging
      voice appear to be factors associated with participation in amateur singing.

PMID- 21889301
TI  - An examination of surface EMG for the assessment of muscle tension dysphonia.
AB  - OBJECTIVES: Muscle tension dysphonia (MTD) is the pathological condition in which
      an excessive tension of the (para)laryngeal musculature leads to a disturbed
      voice. Surface electromyography (sEMG) was used to investigate differences in
      extralaryngeal muscles' tension in patients with MTD compared with normal
      speakers. sEMG was examined as a diagnostic tool to differentiate between
      patients with MTD and controls. METHODS: Eighteen patients with MTD and 44 normal
      speakers were included in the study. All subjects were evaluated with
      videostroboscopy, voice assessment protocol, and sEMG. sEMG was performed on
      three locations of the anterior neck. Measurements were taken during silence,
      phonation tasks, and while reading, with comparisons made between both study
      groups. RESULTS: Patients with MTD did not express higher levels of sEMG during
      rest, phonation, or reading compared with normal speakers. There were no
      significant differences in sEMG values between males and females in both study
      groups. CONCLUSION: sEMG was not able to detect an increase in muscle tension in
      patients with MTD. The results of this study do not support the use of sEMG as a
      diagnostic tool for distinguishing patients with and without MTD. Clinical
      examination with laryngeal palpation, videostroboscopy, and dysphonia severity
      index remain the key investigations.

PMID- 21889300
TI  - The effect of segment selection on acoustic analysis.
AB  - OBJECTIVE/HYPOTHESIS: Acoustic analysis is a commonly used method for
      quantitatively measuring vocal fold function. Voice signals are analyzed by
      selecting a waveform segment and using various algorithms to arrive at parameters
      such as jitter, shimmer, and signal-to-noise ratio (SNR). Accurate and reliable
      methods for selecting a representative vowel segment have not been established.
      STUDY DESIGN: Prospective repeated-measure experiment. METHODS: We applied a
      moving window method by isolating consecutive, overlapping segments of the raw
      voice signal from onset through offset. Ten normal voice signals were analyzed
      using acoustic measures calculated from the moving window. The location and value
      of minimum perturbation/maximum SNR was compared across individuals. The moving
      window method was compared with data from the whole vowel excluding onset and
      offset, the mid-vowel, and the visually selected steadiest portion of the voice
      signal. RESULTS: Results showed that the steadiest portion of the waveforms, as
      defined by minimum perturbation and maximum SNR values, was not consistent across
      individuals. Perturbation and nonlinear dynamic values differed significantly
      based on what segment of the waveform was used. Other commonly used segment
      selection methods resulted in significantly higher perturbation values and
      significantly lower SNR values than those determined by the moving window method
      (P<0.001). CONCLUSIONS: The selection of a sample for acoustic analysis can
      introduce significant inconsistencies into the analysis procedure. The moving
      window technique may provide more accurate and reliable acoustic measures by
      objectively identifying the steadiest segment of the voice sample.

PMID- 21889302
TI  - Can listeners hear who is singing? What is the pitch bandwidth of singer
      discrimination in untrained listeners?
AB  - OBJECTIVE/HYPOTHESIS: This study sought to determine the pitch bandwidth of
      singer discrimination based on singer gender, pitch range, and same-different
      voice category. STUDY DESIGN: Repeated measures factorial design. METHODS: This
      study used a forced-choice paradigm, where listeners heard two different singers
      (singer 1 and singer 2) producing /alpha/ at an identical pitch and an unknown
      singer (either singer 1 or singer 2) producing /alpha/ at a different pitch. It
      was the listener's task to identify which singer (singer 1 or singer 2) was the
      unknown singer. Two baritones and two tenors were recorded producing /alpha/ at
      the pitches C3, E3, G3, B3, D4, and F4. Two sopranos and two mezzo-sopranos were
      recorded producing /alpha/ at the pitches C4, E4, G4, B4, D5, and F5. For each
      group of stimuli, male and female, all possible pairs of singers were constructed
      for the lowest pitch (C2 or C3, respectively) and highest pitch (F4 or F5,
      respectively). The unknown singer was varied across the remaining pitches.
      RESULTS: For between category comparisons, the ability to discriminate singers
      diminished monotonically with pitch interval, reaching below chance levels
      between the intervals of the 9th and 11th. For within category comparisons, it
      was much harder to discriminate singers across pitch, particularly when the
      voices were female. CONCLUSION: Timbre is not perceived as invariant across the
      entire singing range, and the bandwidth of this timbre invariance depends on
      multiple factors, including pitch range, gender, and same-different voice
      category.

PMID- 21889303
TI  - A systematic review of rehabilitation protocols after surgical repair of the
      extensor tendons in zones V-VIII of the hand.
AB  - STUDY DESIGN: Systematic review. INTRODUCTION: Controversy exists as to which
      rehabilitation protocol provides the best outcomes for patients after surgical
      repair of the extensor tendons of the hand. PURPOSE OF THE STUDY: To determine
      which rehabilitation protocol yields the best outcomes with respect to range of
      motion and grip strength in extensor zones V-VIII of the hand. METHODS: A
      comprehensive literature review and assessment was undertaken by two independent
      reviewers. Methodological quality of randomized controlled trials and cohort
      studies was assessed using the Scottish Intercollegiate Guidelines Network scale.
      RESULTS: Seventeen articles were included in the final analysis (kappa=0.9). From
      this total, seven evaluated static splinting, 12 evaluated dynamic splinting, and
      four evaluated early active splinting. Static splinting yielded "excellent/good"
      results ranging from 63% (minimum) to 100% (maximum) on the total active motion
      (TAM) classification scheme and TAM ranging from 185 degrees  (minimum) to 258
      degrees  (maximum) across zones V-VIII. Dynamic splinting studies demonstrated a
      percentage of "excellent/good" results ranging from 81% (minimum) and 100%
      (maximum) and TAM ranging from 214 degrees  (minimum) and 261 degrees  (maximum).
      Early active splinting studies showed "excellent/good" results ranging from 81%
      (minimum) and 100% (maximum). Only one study evaluated TAM in zones V-VIII, which
      ranged from 160 degrees  (minimum) and 165 degrees  (maximum) when using two
      different early active modalities. CONCLUSIONS: The available level 3 evidence
      suggests better outcomes when using dynamic splinting over static splinting.
      Additional studies comparing dynamic and early active motion protocols are
      required before a conclusive recommendation can be made. LEVEL OF EVIDENCE: 2.

PMID- 21889304
TI  - Using short information leaflets as recruitment tools did not improve
      recruitment: a randomized controlled trial.
AB  - OBJECTIVE: To assess if the type of patient information leaflet (PIL) received at
      an initial invitation to participate in a randomized trial influences the number
      of patients recruited. STUDY DESIGN AND SETTING: A randomized controlled trial
      was used to compare the effects of short or full PILs on recruitment in a primary
      care setting. Patients invited to take part in the Randomised Evaluation of the
      Effectiveness and Acceptability of Computerised Therapy study through a database
      mail out were randomly allocated to receive one of two types of PIL. RESULTS: The
      type of PIL received with the initial invitation did not influence recruitment.
      Of those receiving the short PIL, 5.4% were recruited compared with 5.1% in the
      full PIL group. The difference in proportions between the groups was not
      statistically significant (mean difference=0.3%; 95% confidence interval [CI]=
      1.5%, 2.2%; P=0.75). Secondary analyses on the numbers of ineligible patients
      showed a statistically significant difference between the groups in favor of the
      full PIL group, which yielded fewer ineligible patients (P=0.04; mean
      difference=1.4%; CI=0.03%, 2.8%). CONCLUSION: Providing patients with shorter
      PILs when inviting them to participate in research does not affect the numbers
      who are subsequently recruited and yields more ineligible patients. Therefore, it
      is recommended to use the full PIL as a recruitment tool.

PMID- 21889305
TI  - Memory complaint questionnaire performed poorly as screening tool: validation
      against psychometric tests and affective measures.
AB  - OBJECTIVE: This study examined the internal and external validity of the Memory
      Complaint Questionnaire (MAC-Q), a brief measure of subjective memory complaint
      in people with normal cognitive function. STUDY DESIGN AND SETTING: The Study of
      Health Outcomes in Aircraft Maintenance Personnel was a retrospective cohort
      study investigating the association between aircraft fuel tank deseal/reseal
      activities and health status in Royal Australian Air Force personnel. Cross
      sectional comparison tests included measures of executive functioning,
      psychomotor speed, attention/working memory, new learning/memory, depression, and
      anxiety. An adjusted regression analysis accounted for confounders including age,
      dates of posting, rank, education, alcohol use, tobacco use, and affective
      status. RESULTS: Eight hundred seventy-nine participants completed the MAC-Q.
      Although the MAC-Q tested as highly reliable and internally valid, it was highly
      associated with affective status and was only associated with Digit Symbol Coding
      after adjustment for depression/anxiety. CONCLUSION: The MAC-Q is greatly
      influenced by affective status but not memory performance. It is probably not
      useful as a specific screen of memory complaint for general population research.

PMID- 21889306
TI  - Rasch analysis supports the use of the depression, anxiety, and stress scales to
      measure mood in groups but not in individuals with chronic low back pain.
AB  - OBJECTIVE: Chronic pain is a common problem that is associated with mood
      disorders such as depression. The Depression, Anxiety, and Stress Scales (DASS
      21) questionnaire is commonly used to help measure disordered mood. In this
      study, we used Rasch analysis to analyze the clinimetric properties of the DASS
      21 in a chronic low back pain sample. STUDY DESIGN AND SETTING: A Rasch analysis
      was conducted on data collected as a part of a randomized hospital-based placebo
      controlled trial. DASS-21 questionnaires were completed by the 154 enrolled
      participants. RESULTS: The DASS-21 subscales fit the Rasch model. No differential
      item functioning was detected for age, gender, pain severity, or disability.
      Reliability for individual use was supported for the depression subscale (Person
      Separation Index [PSI]=0.86) but group use only for the anxiety (PSI=0.74) and
      stress (PSI=0.82) subscales. A DASS-21 aggregate score of "negative affect"
      lacked fit to the Rasch model (chi(2)=191.48, P<0.001). CONCLUSION: This is the
      first study that used Rasch analysis to demonstrate that the DASS-21 subscales
      demonstrate adequate measurement properties for research involving groups with
      chronic pain. Only the DASS-21 depression subscale demonstrated adequate
      reliability for use with individuals with chronic pain. The use of a single DASS
      21 aggregate score as a measure of "negative affect" was not supported.

PMID- 21889307
TI  - Retrospective cohort study highlighted outcome reporting bias in UK publicly
      funded trials.
AB  - OBJECTIVE: To assess outcome reporting bias and dissemination bias in trials
      funded by the National Health System (NHS) Health Technology Assessment (HTA)
      program. STUDY DESIGN AND SETTING: A retrospective cohort study of HTA monographs
      and corresponding journal publications including all clinical effectiveness
      randomized controlled trials published as HTA monographs between 1999 and 2005 by
      the NHS HTA program. RESULTS: There was a higher median P-value (P=0.33,
      interquartile range [IQR]: 0.02-0.54) among trials without a journal publication
      compared with those with a journal publication (P=0.14, IQR: 0.007-0.43),
      although the difference was not statistically significant (Mann-Whitney U test,
      z=-0.70; P=0.48). A higher proportion of statistically significant findings were
      reported in journal articles when compared with the outcomes reported in the HTA
      monographs. Trials published in general medical journals tended to have smaller P
      values (median: 0.05, IQR: 0.001-0.22) than those published in more specialist
      journals (median: 0.33 IQR: 0.008-0.58), although this result was not significant
      (Mann-Whitney U test, z=-1.63; P=0.10). CONCLUSIONS: Among journal-published
      trials, there were a greater proportion of statistically significant findings
      included in the journal reports compared with those in the HTA monographs.

PMID- 21889308
TI  - Strength of evidence and handling uncertainty: practical considerations and
      general observations.

PMID- 21889309
TI  - Accuracy of self-reported family history is strongly influenced by the accuracy
      of self-reported personal health status of relatives.
AB  - OBJECTIVE: We investigated the accuracy of self-reported family history for
      diabetes, hypertension, and overweight against two reference standards: family
      history based on physician-assessed health status of relatives and on self
      reported personal health status of relatives. STUDY DESIGN AND SETTING: Subjects
      were participants from the Erasmus Rucphen Family study, an extended family study
      among descendants of 20 couples who lived between 1850 and 1900 in a southwest
      region of the Netherlands and their relatives (n=1,713). Sensitivity and
      specificity of self-reported family history were calculated. RESULTS: Sensitivity
      of self-reported family history was 89.2% for diabetes, 92.2% for hypertension,
      and 78.4% for overweight when family history based on relatives' self-reported
      personal health status was used as reference and 70.8% for diabetes, 67.4% for
      hypertension, and 77.3% for overweight when physician-assessed health status of
      relatives was used. Sensitivity and specificity of self-reported personal health
      status were 76.8% and 98.8% for diabetes, 38.9% and 98.0% for hypertension, and
      80.9% and 75.7% for overweight, respectively. CONCLUSION: The accuracy of self
      reported family history of diabetes and hypertension is strongly influenced by
      the accuracy of self-reported personal health status of relatives. Raising
      awareness of personal health status is crucial to ensure the utility of family
      history for the assessment of risk and disease prevention.

PMID- 21889310
TI  - Multivariate graphical methods provide an insightful way to formulate explanatory
      hypotheses from limited categorical data.
AB  - OBJECTIVE: Graphical methods for generating explanatory hypotheses from limited
      categorical data are described and illustrated. STUDY DESIGN AND SETTING:
      Univariate, bivariate, multivariate, and multiplicative graphical methods were
      applied to clinical data regarding very ill older persons. The data to which
      these methods were applied were limited as to their nature (e.g., nominal
      categorical data) or quality (e.g., data subject to measurement error and missing
      values). Such limitations make confirmatory inference problematic but might still
      allow for meaningful generation of new explanatory hypotheses in some cases.
      RESULTS: A striking feature of the graphical results from this study's major
      illustrative application was that posttraumatic stress disorder (PTSD) after
      intensive care unit discharge occurred rarely and nearly always co-occurred with
      two or more other mental health conditions. These results suggest the explanatory
      hypothesis that PTSD in this context is less attributable to single traumatic
      causes than to acute illnesses contributing to a cascade of mental health
      decrements. CONCLUSION: Illustrative applications of a sequence of graphical
      procedures yield more informative and less abstract representations of limited
      data than do descriptive statistics alone, and by doing so, they aid in the
      formulation of explanatory hypotheses.

PMID- 21889311
TI  - Development of temporomandibular joint ankylosis in rats using stem cells and
      bone graft.
AB  - 64 male Wistar rats were used: 24 for the removal of stem cells, 4 as a control
      group, and 36 for the experiment, in which either stem cells or bone graft was
      used. The rats were divided into groups according to the type of procedure and
      time span (15, 30 or 60 days). The joints were submitted to histological study in
      order to score the ankylosis. The mean differences between initial and final
      maximal mouth opening (MMO) were gradually increased from 15 to 60 days, for all
      times of evaluation for both groups, being statistically significant at 15 days
      (p=0.045) in the bone-graft group. When both groups were compared, the mean
      differences between initial and final MMO were statistically significant at 15
      days (p=0.018) and 30 days (p=0.029). In relation to the histological scores, in
      the bone-graft group almost all animals had intra-articular fibrosis at all times
      of evaluation (n=17). In the stem-cell group, there was new bone at 15 days
      (n=4), 30 days (n=3) and 60 days (n=4). The study model permitted the development
      of fibrous ankylosis in the majority of animals for both groups and no bony
      bridge was observed.

PMID- 21889312
TI  - Temporomandibular disorders in patients with mandibular fractures: a preliminary
      comparative case-control study between South Australia and Oman.
AB  - The status of temporomandibular disorders (TMD) in subjects with previously
      treated mandibular fracture was evaluated in two centres: South Australia (SA)
      and Oman (O). TMD status was evaluated using Mandibular Function Impairment
      Questionnaire (MFIQ), Helkimo index for clinical dysfunction (HI), RDC/TMD and
      Wilkes' classification. Data were retrieved for adult patients treated for
      mandibular fracture over 3 years from January 2004 to December 2006. Thirty-six
      subjects participated from SA and 23 from O. Their results were compared with
      matched controls. The incidence of TMD symptoms in SA injured and control groups
      was higher compared with the O groups. There was statistically significant
      difference on all evaluation indices for SA injured subjects compared with
      controls (MFIQ/P 0.04, HI/P 0.0015, RDC/TMD/P 0.05, Wilkes classification/P
      0.03). These TMD symptoms were clinically insignificant for most subjects and all
      were internal derangement of the temporomandibular joint (TMJ). There was no
      significant difference in all evaluation indices for O injured subjects compared
      with controls. For SA injured subjects who reported clinically significant TMD
      symptoms, assault and bilateral mandibular fractures were predominant features.
      The study shows that most mandibular injuries fully recover and the associated
      TMJ trauma usually has low clinical significance in the long term.

PMID- 21889313
TI  - Chlamydia pneumoniae heat shock protein 60 is associated with apoptotic signaling
      pathway in human atheromatous plaques of coronary artery disease patients.
AB  - BACKGROUND: Chlamydia pneumoniae heat shock protein (HSP) 60 is known to
      contribute to the activation of inflammation. In addition, there are
      contradictory reports on C. pneumoniae and their role in activation of pathways
      (apoptotic/antiapoptotic/necrosis) in coronary artery disease (CAD). Hence, more
      studies are required to know the actual role of C. pneumoniae in activation of
      apoptotic/antiapoptotic/necrosis pathways. METHODS AND RESULTS: In this study,
      two sets of patient groups (cHSP60 positive and cHSP60 negative) were included
      and gene expression was studied by cDNA micro array and real time polymerase
      chain reaction arrays. Expression of Caspase-3, 8, 9, c-FLIP, PPAR-gamma, PGC
      1alpha, and Gsk-3b were also evaluated at protein level by immunoblotting. In
      cHSP60 positive CAD patients significantly higher (p<0.001) mRNA expression was
      found for CCL4, CXCL4, CXCL9, IL-8, CD40LG, CD8, TGFbeta1, TGFbeta2, APOE, EGR1,
      CTGF, APOB, LDLR, LPA, and LPL, whereas significantly lower (p<0.001) mRNA
      expression was detected for CD4, IL1F10, IFNA2, and IL-10 as compared to cHSP60
      negative CAD patients. Additionally, at protein level expression of Caspase-3
      (p=0.027), 8 (p=0.028), and 9 (p=0.037) were higher and c-FLIP (p=0.028) and PPAR
      gamma (p=0.95) expression were comparable in cHSP60 positive CAD patients
      compared to cHSP60 negative CAD patients. CONCLUSION: Genes/proteins of pre
      apoptotic caspase dependent/independent pathways, chemokines, and inflammatory
      cytokines receptors were significantly up-regulated in human atheromatous plaques
      of cHSP60 positive CAD patients suggesting an association of cHSP60 with CAD.

PMID- 21889314
TI  - Fast activity during EEG seizures in neonates.
AB  - INTRODUCTION: Paroxysmal fast activity (FA) has been proposed as a marker for
      epileptic networks. We explore the presence and significance of ictal FA on scalp
      video EEG seizures (EEG Sz) recorded in neonates. METHODOLOGY: Forty two babies
      had 159 EEG Szs. The seizures were analysed for ictal FA, using a low frequency
      filter of 30 Hz. We explored the relationship of ictal FA to the occurrence of
      electroclinical and electrographic seizures, the use of phenobarbitone and to
      neurodevelopmental outcomes. RESULTS: Ictal FA occurred in 62 (39%) of the 159
      EEG Szs. In the 62 seizures with ictal FA, 34 (55%) were electroclinical seizures
      (ECSz) and 28 (45%) were electrographic (ESz). In the remaining 97 seizures
      without ictal FA, 27 (28%) were ECSz and 70 (72%) ESz. There was a significant
      correlation (p=0.0006) between ictal FA and electroclinical seizures. There was
      no relationship between phenobarbitone and presence of ictal FA. There was no
      significant difference in the background EEG, neuroimaging abnormalities,
      neurodevelopmental impairment or post neonatal seizures between those with and
      without ictal FA. CONCLUSIONS: Ictal FA is highly correlated to the occurrence of
      clinical features during an EEG seizure. The presence of ictal FA does not appear
      to influence neurodevelopmental outcomes.

PMID- 21889315
TI  - Transition to absence seizures and the role of GABA(A) receptors.
AB  - Absence seizures appear to be initiated in a putative cortical 'initiation site'
      by the expression of medium-amplitude 5-9Hz oscillations, which may in part be
      due to a decreased phasic GABA(A) receptor function. These oscillations rapidly
      spread to other cortical areas and to the thalamus, leading to fully developed
      generalized spike and wave discharges. In thalamocortical neurons of genetic
      models, phasic GABA(A) inhibition is either unchanged or increased, whereas tonic
      GABA(A) inhibition is increased both in genetic and pharmacological models. This
      enhanced tonic inhibition is required for absence seizure generation, and in
      genetic models it results from a malfunction in the astrocytic GABA transporter
      GAT-1. Contradictory results from inbred and transgenic animals still do not
      allow us to draw firm conclusions on changes in phasic GABA(A) inhibition in the
      GABAergic neurons of the nucleus reticularis thalami. Mathematical modelling may
      enhance our understanding of these competing hypotheses, by permitting
      investigations of their mechanistic aspects, hence enabling a greater
      understanding of the processes underlying seizure generation and evolution.

PMID- 21889316
TI  - Prenatal exposure to bacterial endotoxin reduces the number of GAD67- and reelin
      immunoreactive neurons in the hippocampus of rat offspring.
AB  - Epidemiological studies implicate prenatal infection as a risk factor for the
      development of schizophrenia and autism. Subjects with schizophrenia and autism
      are reported to exhibit reduced levels of glutamic acid decarboxylase 67 (GAD67),
      a marker for GABA neurons, in various brain regions. Reduced levels of reelin, a
      secretory glycoprotein present in a subpopulation of GABA neurons, have also been
      found in these disorders. To test if prenatal infection can cause abnormalities
      in GAD67 and reelin in the brains of offspring, this study used a rat model of
      prenatal exposure to the bacterial endotoxin, lipopolysaccharide (LPS), and
      assessed numbers of GAD67-immunoreactive (GAD67+) and reelin-immunoreactive
      (reelin+) neurons in the hippocampus of offspring. In offspring at postnatal day
      14 (PD14), GAD67+ cell counts were reduced in the dentate gyrus of the prenatal
      LPS group compared to prenatal saline controls, while at PD28, GAD67+ cells
      counts were reduced in the prenatal LPS group in both the dentate gyrus and the
      CA1. There was a decrease in the number of reelin+ cells in the prenatal LPS
      offspring compared to controls in the dentate gyrus at PD14. However using
      Western blotting, no significant effects of prenatal LPS on levels of GAD67 or
      reelin protein were observed in various brain regions at PD14. These findings
      support the idea that prenatal infection can cause reductions in postnatal
      expression of GAD67 and reelin, and in this way, possibly contribute to the
      pathophysiology of schizophrenia or autism.

PMID- 21889317
TI  - Triple monoamine inhibitor tesofensine decreases food intake, body weight, and
      striatal dopamine D2/D3 receptor availability in diet-induced obese rats.
AB  - The novel triple monoamine inhibitor tesofensine blocks dopamine, serotonin and
      norepinephrine re-uptake and is a promising candidate for the treatment of
      obesity. Obesity is associated with lower striatal dopamine D2 receptor
      availability, which may be related to disturbed regulation of food intake. This
      study assesses the effects of chronic tesofensine treatment on food intake and
      body weight in association with changes in striatal dopamine D2/D3 receptor
      (D2/3R) availability of diet-induced obese (DIO) rats. Four groups of 15 DIO rats
      were randomized to one of the following treatments for 28 days: 1. tesofensine
      (2.0 mg/kg), 2. vehicle, 3. vehicle+restricted diet isocaloric to caloric intake
      of group 1, and 4. tesofensine (2.0 mg/kg)+ a treatment-free period of 28 days.
      Caloric intake and weight gain decreased significantly more in the tesofensine
      treated rats compared to vehicle-treated rats, which confirms previous findings.
      After treatment discontinuation, caloric intake and body weight gain gradually
      increased again. Tesofensine-treated rats showed significantly lower D2/3R
      availability in nucleus accumbens and dorsal striatum than both vehicle-treated
      rats and vehicle-treated rats on restricted isocaloric diet. No correlations were
      observed between food intake or body weight and D2/3R availability. Thus, chronic
      tesofensine treatment leads to decreased food intake and weight gain. However,
      this appears not to be directly related to the decreased striatal D2/3R
      availability, which is mainly a pharmacological effect.

PMID- 21889318
TI  - Effects of the relative humidity and water droplet on adhesion of a bio-inspired
      nano-film.
AB  - Inspired by geckos' adhesion, the effect of water membrane forming due to the
      environmental humidity, on the adhesion between a bio-inspired nano-film and a
      substrate is investigated first. The disjoining pressure is considered, which
      results in an enhancing adhesion between the nano-film and substrate. When the
      thickness of water membrane increases, water droplets will form and a repulsive
      capillary force between the nano-film and substrate is produced. The total
      adhesion force decreases with an increasing volume of water droplets. The two
      opposite results in the two different models are consistent well with two
      seemingly inconsistent experimental observations by Huber et al. (2005) [4] and
      Sun et al. (2005) [5], respectively, and may be significant for the development
      of artificial biomimetic attachment systems.

PMID- 21889319
TI  - [Intrafamilial transmission of Staphylococcus aureus Panton-Valentine leukocidin
      responsible for two cases of neonatal necrotizing pneumonia].
AB  - Necrotizing Staphylococcus aureus Panton-Valentine leukocidin (SA-PLV+) accounts
      for less than 1% of community-acquired lung diseases in children and young
      adults. Neonatal cases are exceptional. We report the observations of two newborn
      female twins, who were not breastfed, presenting a necrotizing lung disease due
      to the same strain of SA-PVL+ despite nasal decolonization measures taken. These
      two cases are informative and bring to light (1) the possibility of severe SA
      PVL+ lung infections in young infants and (2) their strictly intrafamilial mode
      of transmission for which eradication measures were ineffective.

PMID- 21889320
TI  - [Neonatal renal venous thrombosis: the recent experience of Robert-Debre
      hospital].
AB  - Neonatal renal venous thrombosis (NRVT) is a rare disease, with variable
      consequences on kidney function. We report a retrospective study of 9 newborns
      with NRVT admitted to our hospital from 1996 to 2005. The median age at diagnosis
      was 2 days (range, 1-10 days). In 7 patients, diagnosis was suspected based on
      one classical clinical or biological sign and was confirmed by ultrasound. Seven
      newborns had at least one known obstetrical or neonatal risk factor. NRVT was
      unilateral in three cases, was bilateral in 6 cases, and was associated with
      inferior vena cava thrombosis in 5 patients, with surrenal hemorrhage in 3
      patients. Three patients did not receive specific treatment. The median delay
      between diagnosis and specific treatment was 20 h (range, 3-36 h). Three patients
      were treated by fibrinolysis, including 2 with bilateral NRVT, 2 newborns
      received heparins, and 1 patient was treated with a vitamin K antagonist. With a
      median evaluation time of 5 years and 2 months for 6 patients, 5 patients
      recovered their kidney function completely and the 6th child has moderate renal
      failure. It seems illusory to wait for randomized control studies to appreciate
      the potential long-term benefit of treatments on kidney function after a NRVT,
      whose bilateral forms appear to be more severe. A case-by-case approach appears
      better adapted. These results reinforce recommendations that suggest an early
      pediatric nephrologic follow-up for all newborns with a NRVT.

PMID- 21889321
TI  - [A rare complication of Streptococcal B meningitis in a newborn: central diabetes
      insipidus].

PMID- 21889322
TI  - Sex determination of Joseon people skeletons based on anatomical, cultural and
      molecular biological clues.
AB  - Sex determination is very integral to examinations conducted by anatomists on
      human skeletons discovered in the archaeological field. In Korea, as in other
      countries, cultural or anatomical information has been the tool of first resort
      in making such determinations. In cases in which anatomical examination has
      revealed only borderline characteristics, PCR-based analysis of X/Y-chromosome
      genes has been employed. Even so, there are as yet very few reports on how
      accurately the respective results correspond with each other. In this study on 34
      examined medieval Korean skeletons, 11 (32.3%) showed perfectly matching results
      for the three methods of sex determination. In the cases in which the cultural
      and anatomical findings were discordant, the amelogenin assay corroborated either
      the former or the latter. Although we must admit the relatively limited role of
      aDNA analysis, when only very small amounts of amplifiable DNA remain, we believe
      that the amelogenin assay can be very meaningful to Korean anatomists when
      employed in adjunct to conventional anatomically or culturally based sex
      determination.

PMID- 21889324
TI  - Plasma levels of neuropeptides and metabolic hormones, and sleepiness in
      obstructive sleep apnea.
AB  - BACKGROUND: Obstructive sleep apnea (OSA) is related to obesity and metabolic
      disorders. The main clinical symptoms are excessive daytime sleepiness (EDS) and
      snoring. However, not all patients with OSA manifest EDS. Hypocretin-1,
      neuropeptide Y, leptin, ghrelin and adiponectin are implicated in both metabolic
      and sleep regulation, two conditions affected by OSA. We hypothesized that levels
      of these peptides may be related to EDS in OSA patients. METHODS: We included 132
      patients with EDS, as defined by an Epworth Sleepiness Scale (ESS) score >= 13
      (mean +/- SD, 15.7 +/- 2.3) and 132 patients without EDS as defined by an ESS
      score <= 9 (6.5 +/- 1.9). All patients had an apnea-hypopnea index (AHI) >= 20 h(
      1). Both groups were matched for gender (males; 83.3% vs. 85.6%), age (50.15 +/-
      11.2 yrs vs. 50.7 +/- 9.9 yrs), body mass index (BMI) (31.8 +/- 5.6 kg m(-2) vs.
      32.1 +/- 4.8 kg m(-2)), and apnea-hypopnea index (AHI) (45.5 +/- 19.1 h(-1) vs.
      43 +/- 19.2 h(-1)). RESULTS: OSA patients with EDS showed significantly higher
      plasma hypocretin-1 levels (p < 0.001) and lower plasma ghrelin levels (p <
      0.001) than OSA patients without EDS. There were no statistically significant
      differences in neuropeptide Y (p = 0.08), leptin (p = 0.07) and adiponectin (p =
      0.72) between the two groups. In the multiple linear regression model ESS score
      was associated with plasma levels of hypocretin-1, ghrelin and total sleep time.
      CONCLUSION: Our study shows that EDS in patients with OSA is associated with
      increased circulating hypocretin-1 and decreased circulating ghrelin levels, two
      peptides involved in the regulation of body weight, energy balance, sympathetic
      tone and sleep-wake cycle. This relationship is independent of AHI and obesity
      (two key phenotypic features of OSA).

PMID- 21889325
TI  - GOLD COPD stage I is not associated with increased risk of death.

PMID- 21889323
TI  - IL-2 family cytokines: new insights into the complex roles of IL-2 as a broad
      regulator of T helper cell differentiation.
AB  - Interleukin-2 (IL-2) is a pleiotropic cytokine that drives T-cell growth,
      augments NK cytolytic activity, induces the differentiation of regulatory T
      cells, and mediates activation-induced cell death. Along with IL-4, IL-7, IL-9,
      IL-15, and IL-21, IL-2 shares the common cytokine receptor gamma chain, gamma(c),
      which is mutated in humans with X-linked severe combined immunodeficiency.
      Herein, we primarily focus on the recently discovered complex roles of IL-2 in
      broadly modulating T cells for T helper cell differentiation. IL-2 does not
      specify the type of Th differentiation that occurs; instead, IL-2 modulates
      expression of receptors for other cytokines and transcription factors, thereby
      either promoting or inhibiting cytokine cascades that correlate with each Th
      differentiation state. In this fashion, IL-2 can prime and potentially maintain
      Th1 and Th2 differentiation as well as expand such populations of cells, whereas
      it inhibits Th17 differentiation but also can expand Th17 cells.

PMID- 21889326
TI  - Analysis of energy recovery potential using innovative technologies of waste
      gasification.
AB  - In this paper, two alternative thermo-chemical processes for waste treatment were
      analysed: high temperature gasification and gasification associated to plasma
      process. The two processes were analysed from the thermodynamic point of view,
      trying to reconstruct two simplified models, using appropriate simulation tools
      and some support data from existing/planned plants, able to predict the energy
      recovery performances by process application. In order to carry out a comparative
      analysis, the same waste stream input was considered as input to the two models
      and the generated results were compared. The performances were compared with
      those that can be obtained from conventional combustion with energy recovery
      process by means of steam turbine cycle. Results are reported in terms of energy
      recovery performance indicators as overall energy efficiency, specific energy
      production per unit of mass of entering waste, primary energy source savings,
      specific carbon dioxide production.

PMID- 21889327
TI  - Define baseline levels of segments per beam for intensity-modulated radiation
      therapy delivery for brain, head and neck, thoracic, abdominal, and prostate
      applications.
AB  - The purpose of this study was to evaluate the number of segments per beam for
      intensity-modulated radiation therapy (IMRT) treatments and its effects on the
      plan quality, treatment delivery time, machine quality assurance, and machine
      maintenance. We have retrospectively analyzed 24 patients treated with IMRT. Five
      were selected within each of the following regions: head and neck, thoracic,
      abdomen, and prostate. Four patients were optimized within the brain region. The
      clinically treated plans were re-optimized using Philips Pinnacle3 v. 8 with the
      direct machine parameter optimization algorithm. The number of segments per beam
      from the treated plan was systematically reduced by 80%, 60%, 40%, and 30%, and
      the following statistics have been analyzed for plan quality: target min, mean,
      and max doses; critical structure doses; and integral dose. We have attempted to
      define the smallest number of segments per beam for IMRT treatment plans. Results
      indicate that IMRT plans can be delivered with acceptable quality with
      approximately 3-6 segments per beam for the anatomical regions analyzed. A
      reduction in the number of segments decreases treatment delivery time, reduces
      machine wear and tear, and minimizes the amount of time the patient is on the
      treatment table, which in turn reduces the chances of intrafractional
      uncertainties.

PMID- 21889328
TI  - Olfactory networks: from sensation to perception.
AB  - Olfactory networks, comprised of sensory neurons and interneurons, detect and
      process changes in the chemical environment to drive animal behavior. Recent
      studies combining genetics with behavioral analyses and imaging in worms, flies
      and mice have revealed new insights into the mechanisms of olfaction. In this
      discussion, we focus on three interesting findings. First, sensory neuron
      responses to odor are modulated by neuropeptides. This modulation might serve to
      extend the range of responses of the sensory neurons and also to integrate
      internal state information into the chemosensory circuit. Second, genetic tracing
      studies in mice and flies have shown that the first layer of connections in
      chemosensory circuits from olfactory epithelium to the glomeruli are stereotyped,
      while the subsequent connections to higher order sensory processing regions are
      not. Distributed connectivity to the higher order sensory processing regions has
      profound implications for how odors are represented in those regions. Third,
      recent work has revealed that odors are surprisingly sparsely represented in the
      piriform cortex. The sparse coding in the higher brain centers implies a much
      greater role for experience and learning in mediating responses to olfactory
      cues. Analyzing olfactory network function in various species provides us with
      fascinating clues about how sensory information is acquired, processed and
      represented at multiple levels within the nervous system.

PMID- 21889329
TI  - Post-translational regulation of signaling mucins.
AB  - Signaling mucins are large transmembrane glycoproteins that regulate signal
      transduction pathways. Recent advances have shown that two major types of post
      translational modifications, protein glycosylation and proteolytic processing,
      play important and unexpected roles in regulating signaling mucin function. New O
      glycosyltransferases and proteases have been identified, and the structure of the
      domain that undergoes auto-proteolysis has been solved. A picture is beginning to
      emerge where specific glycosyl modifications and regulated processing control the
      signaling and adherence properties of signaling glycoproteins and contribute to
      the routing of signals to specific pathways.

PMID- 21889330
TI  - Key predictive factors of axitinib (AG-013736)-induced proteinuria and efficacy:
      a phase II study in Japanese patients with cytokine-refractory metastatic renal
      cell Carcinoma.
AB  - BACKGROUND: Axitinib (AG-013736) is an oral, selective and potent inhibitor of
      vascular endothelial growth factor receptors (VEGFR)-1, 2 and 3. This phase II
      study investigated axitinib efficacy, safety and biomarkers in Japanese patients
      with cytokine-refractory metastatic renal cell carcinoma (mRCC). PATIENTS AND
      METHODS: In an open-label, multicentre study, 64 patients received an axitinib
      starting dose of 5mg twice daily. RESULTS: Objective response rate (ORR) was
      50.0% and median progression-free survival (PFS) was 11.0 months per independent
      review committee. Common treatment-related adverse events were hypertension (84%;
      70% grade >=3), hand-foot syndrome (75%; 22% grade >=3) and diarrhoea (64%; 5%
      grade >=3). Eighteen patients (28%) developed proteinuria >=2g/24h and required
      dose reduction or treatment interruption/discontinuation. Proteinuria was a major
      cause for treatment discontinuation. Baseline urine protein levels were
      associated with development of proteinuria >=2g/24h (hazard ratio [HR]=5.457,
      P=0.0035 in patients with baseline proteinuria >=1+ versus <1+). Baseline urine
      protein levels correlated more strongly with axitinib-related proteinuria than
      other baseline renal function test values or blood pressure. Patients with
      greater decreases in soluble VEGFR-2 concentrations had significantly higher ORR
      and longer PFS than those with smaller decreases (ORR: 64.5% versus 37.5%,
      P=0.045; median PFS: 12.9 months versus 9.2 months, HR=0.42, P=0.01).
      CONCLUSIONS: Axitinib showed significant antitumour activity and was well
      tolerated in Japanese mRCC patients. Baseline proteinuria and soluble VEGFR-2
      levels may be key indicators of axitinib-induced proteinuria and efficacy,
      respectively.

PMID- 21889331
TI  - Glutamine inhibits platelet-activating factor-mediated pulmonary tumour
      metastasis.
AB  - Inflammation has been increasingly recognised as an important component of
      tumourigenesis. Platelet-activating factor (PAF), a potent inflammatory mediator,
      has the ability to enhance tumour growth and metastasis. In this study, we have
      investigated (i) the role of mitogen-activated protein kinases (MAPKs) and (ii)
      the therapeutic efficacy of the non-essential amino acid, l-glutamine (Gln),
      which evidences MAPKs inhibition activity in PAF-mediated B16F10 melanoma
      metastasis to the lungs. Mice were given intraperitoneal injection of PAF. ERK,
      JNK, and p38 MAPKs were activated rapidly by PAF in the lungs, and the PAF
      induced metastasis of B16F10 was inhibited in a dose-dependent manner by
      pretreatment with either U0126 (ERK inhibitor), SP600125 (JNK inhibitor), or
      SB202190 (p38 inhibitor). Intraperitoneal administration of Gln after, but not
      before, PAF injection deactivated ERK, JNK, and p38 by dephosphorylating them.
      Gln inhibited PAF-induced metastasis when Gln was administered either
      intraperitoneally or orally. PAF induced pronounced angiogenic activity in an in
      vivo mouse Matrigel implantation model. MAPK inhibitors as well as Gln
      significantly inhibited PAF-induced angiogenesis. These data indicate that Gln
      exerts a beneficial effect against inflammation-associated enhanced tumour
      metastasis via the deactivation of MAPKs.

PMID- 21889332
TI  - Type 2 diabetes mellitus and colorectal cancer: meta-analysis on sex-specific
      differences.
AB  - Although there is consent concerning a higher risk for colorectal cancer (CRC)
      amongst patients with type 2 diabetes mellitus (T2DM), there remains uncertainty
      regarding potential sex differences in the strength of this association. We
      reviewed and summarised epidemiological studies assessing the sex-specific
      association of T2DM with the risk for CRC. All relevant studies published until
      14th February 2011 were identified by a systematic search of MEDLINE, EMBASE,
      BIOSIS Previews and ISI Web of Knowledge databases and cross-referencing. We
      included observational studies that reported relative risk (RR) or odds ratio
      (OR) estimates with 95% confidence intervals (CIs) for the association between
      T2DM and CRC. Two authors independently extracted data and assessed study quality
      of each study in a standardised manner. Study-specific estimates were pooled for
      both sexes separately using random-effects models. A total of 29 eligible studies
      were used for meta-analysis. Overall estimates of relative risk (RR) were very
      similar amongst men (RR=1.29; 95%-confidence interval (CI): 1.19-1.140) and women
      (RR=1.34; 95%-CI: 1.22-1.47). In both men and women, risk estimates from case
      control studies were slightly higher than those from cohort studies. Overall,
      T2DM is associated with a moderate increase in CRC risk in both men and women.

PMID- 21889333
TI  - Discovery of potent, metabolically stable purine CRF-1 antagonists with
      differentiated binding kinetic profiles.
AB  - Optimisation of the potency of a bicyclic CRF antagonist whilst retaining
      metabolic stability is described. A core change and incorporation of
      metabolically stable lipophilic groups resulted in a further potency gain without
      increasing metabolic liability. Pharmacological investigation of binding kinetics
      led to the identification of compound 25, a sub-nanomolar CRF-1 antagonist with
      slow dissociation kinetics and an encouraging pharmacokinetic profile.

PMID- 21889334
TI  - Design, synthesis and X-ray crystallographic study of new nonsecosteroidal
      vitamin D receptor ligands.
AB  - We designed and synthesized nonsecosteroidal vitamin D receptor (VDR) ligands
      that formed H-bonds with six amino acid residues (Tyr143, Ser233, Arg270, Ser274,
      His301 and His393) of the VDR ligand-binding domain. The ligand YR335 exhibited
      potent transcriptional activity, which was comparable to those of 1alpha,25
      dihydroxyvitamin D(3) and YR301. The crystal structure of the complex formed
      between YR335 and the VDR ligand-binding domain was solved, which revealed that
      YR335 formed H-bonds with the six amino acid residues mentioned above.

PMID- 21889335
TI  - Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and
      their pharmacologies. Part 2: Synthesis of novel triplet drugs with the
      epoxymethano structure (capped homotriplet).
AB  - An improved synthetic method for triplet drugs with the 1,3,5-trioxazatriquinane
      skeleton was developed that used p-toluenesulfonylmethyl isocyanide (TosMIC)
      instead of 1,3-dithiane. Using the improved method, we synthesized compounds with
      two identical pharmacophore units and an epoxymethano group, that is, capped
      homotriplets. Among the synthesized capped homotriplets, KNT-123 showed high
      selectivity for the MU receptor over the kappa receptor, and the MU selectivity
      was the highest among the reported MU selective nonpeptide ligands. KNT-123
      administered subcutaneously induced a dose-dependent analgesic effect in the
      acetic acid writhing assay, and its potency was 11-fold more potent than that of
      morphine. KNT-123 may serve as a useful tool for the study of the pharmacological
      actions mediated specifically via the MU receptor.

PMID- 21889336
TI  - Oleanane-type triterpene saponins from the bark of Aralia elata and their NF
      kappaB inhibition and PPAR activation signal pathway.
AB  - Two new oleanane-type triterpene saponins, tarasaponin IV (1) and elatoside L
      (2), and four known; stipuleanoside R(2) (3), kalopanax-saponin F (4), kalopanax
      saponin F methylester (5), and elatoside D (6) were isolated from the bark of
      Aralia elata. Kalopanax-saponin F methyl ester was isolated from nature for the
      first time. Their chemical structures were elucidated using the chemical and
      physical methods as well as good agreement with those of reported in the
      literature. Oleanane-type triterpene saponins are the main component of A. elata.
      All compounds were investigated the anti-inflammatory activity. We measured their
      inhibition of NF-kappaB and activation of PPARs activities in HepG2 cells using
      luciferase reporter system. As results, compounds 2 and 4 were found to inhibit
      NF-kappaB activation stimulated by TNFalpha in a dose-dependent manner with
      IC(50) values of 4.1 and 9.5 MUM, respectively, when compared with that of
      positive control, sulfasalazine (0.9 MUM). Compounds 2 and 4 also inhibited
      TNFalpha-induced expression of iNOS and COX-2 mRNA. Furthermore, compounds 1-6
      were evaluated PPAR activity using PPAR subtype transactivation assays. Among of
      them, compounds 4-6 significantly increased PPARgamma transactivation. However,
      compounds 4-6 did not activate in any other PPAR subtypes.

PMID- 21889337
TI  - Inhibition of xc- transporter-mediated cystine uptake by sulfasalazine analogs.
AB  - A series of sulfasalazine analogs were synthesized and tested for their ability
      to block cystine-glutamate antiporter system xc- using L-[(14)C]cystine as a
      substrate. Replacement of sulfasalazine's diazo group with an alkyne group led to
      an equally potent inhibitor, 2-hydroxy-5-((4-(N-pyridin-2
      ylsulfamoyl)phenyl)ethynyl)benzoic acid 6. Our SAR studies also revealed that the
      carboxylate group of sulfasalazine is essential for its inhibitory activity while
      the phenolic hydroxyl group is dispensable. Truncated analogs lacking an N
      pyridin-2-ylsulfamoyl moiety were less potent than sulfasalazine, but may serve
      as more tractable templates because of their low molecular weight by applying a
      variety of fragment growing approaches. Given that sulfasalazine is rapidly
      metabolized through cleavage of the diazo bond, these analogs may possess a more
      desirable pharmacological profile as system xc- blockers, in particular, for in
      vivo studies.

PMID- 21889338
TI  - Synthesis and evaluation of phosphoramidate and phosphorothioamidate analogues of
      amiprophos methyl as potential antimalarial agents.
AB  - A series of phosphoramidate and phosphorothioamidate compounds based on the lead
      antitubulin herbicidal agents amiprophos methyl (APM) and butamifos were
      synthesised and evaluated for antimalarial activity. Of these compounds,
      phosphorothioamidates were more active than their oxo congeners and the nature of
      both aryl and amido substituents influenced the desired activity. The most active
      compound was 46, O-ethyl-O-(2-methyl-4-nitrophenyl)-N-cyclopentyl
      phosphorothioamidate, which was more effective than the lead compound.

PMID- 21889339
TI  - Benzotriazinone and benzopyrimidinone derivatives as potent positive allosteric
      AMPA receptor modulators.
AB  - AMPA receptors (AMPARs) have been demonstrated to be an important therapeutic CNS
      target. A series of substituted benzotriazinone and benzopyrimidinone derivatives
      were prepared with the aim to improve in vivo activity over the previously
      reported bis-benzoxazinone based AMPAKINE series from our laboratory. These
      compounds were shown to be potent, positive allosteric AMPAR modulators that have
      better in vivo activity and improved metabolic stability over the analogous
      benzoxazinone derivatives.

PMID- 21889340
TI  - Dinucleotide cap analogue affinity resins for purification of proteins that
      specifically recognize the 5' end of mRNA.
AB  - Here we present first dinucleotide affinity resins for purification of proteins
      that specifically recognize the 5' end of mRNA. Constructed resins possess either
      a naturally occurring mono- or trimethylated cap or their analogues resistant
      towards enzymatic degradation, bearing a CH(2) bridge between beta and gamma
      position of the 5',5'-triphosphate chain. All cap analogues were attached to a
      polymer support (EAH-Sepharose) through the carboxylic group that had been
      generated by derivatization of the 2',3'-cis diol of the second nucleotide in the
      cap structure with levulinic acid.

PMID- 21889341
TI  - Novel 4-azasteroidal N-glycoside analogues bearing sugar-like D ring: synthesis
      and anticancer activities.
AB  - A series of novel N-glycoside analogues with 4-azasteroid moiety bearing sugar
      like D ring were conveniently synthesized by constructing the core dihydropyran
      ring embedded in 4-azasteroidal skeleton which was prepared from 4-aza-5alpha
      androst-3,17-dione 1 in four steps. The structure of 6b were unambiguously proved
      by the appropriate X-ray structural analysis. Anticancer activity was found for
      all of the analogues with purinyl moiety against breast cancer (MCF-7), human
      neuroblastoma (SK-N-SH), cervical cancer cell (HeLa) and prostatic cancer (PC-3),
      while the analogue 7 containing 1,2,4-triazole heterocycle as the nucleobase was
      inactive against all of the tested cancer cell lines. The biology results showed
      the purinyl moiety attached to the pyran ring of 6a-d, substituent at 6'-position
      of purine base and introduction of a halogen atom at 2'-position of 6'
      chloropurine had obviously effect on the evaluated anticancer activity.

PMID- 21889342
TI  - Ferrocenyl chalcone difluoridoborates inhibit HIV-1 integrase and display low
      activity towards cancer and endothelial cells.
AB  - We report here the discovery of a potent series of HIV-1 integrase (IN)
      inhibitors based on the ferrocenyl chalcone difluoridoborate structure. Ten new
      compounds have been synthesized and were generally found to have similar
      inhibitory activities against the IN 3' processing and strand transfer (ST)
      processes. IC(50) values were found to be in the low micromolar range, and
      significantly lower than those found for the non-coordinated ferrocenyl chalcones
      and other ferrocene molecules. The ferrocenyl chalcone difluoridoborates
      furthermore exhibited low cytotoxicity against cancer cells and low morphological
      activity against epithelial cells.

PMID- 21889343
TI  - The structural requirements of histone deacetylase inhibitors: Suberoylanilide
      hydroxamic acid analogs modified at the C3 position display isoform selectivity.
AB  - The FDA-approved drug suberoylanilide hydroxamic acid (SAHA, Vorinostat) was
      modified to improve its selectivity for a single histone deaetylase (HDAC)
      isoform. We show that attaching an ethyl group at the C3 position transforms SAHA
      from nonselective to an HDAC6-selective inhibitor. Theses results indicate that
      small structural changes in SAHA can significantly influence selectivity, which
      will lead future anti-cancer design efforts targeting HDAC proteins.

PMID- 21889344
TI  - Acylglycinamides as inhibitors of glycine transporter type 1.
AB  - A screening hit was used as the basis for the core structure of a new series of
      acylglycinamide GlyT-1 inhibitors. Investigation of the SAR around four areas of
      diversity used facile chemistry to prepare compounds quickly. By focussing on
      reducing the lipophilicity and improving the aqueous solubility in the series we
      were able to prepare a compound (17e) with a good level of activity at GlyT-1,
      selectivity over GlyT-2 and moderate oral bioavailability.

PMID- 21889345
TI  - Synthesis, biological evaluation and molecular docking studies of 1,3,4
      thiadiazole derivatives containing 1,4-benzodioxan as potential antitumor agents.
AB  - A series of 1,3,4-thiadiazole derivatives containing 1,4-benzodioxan (2a-2s) have
      been synthesized to screen for FAK inhibitory activity. Compound 2p showed the
      most potent biological activity against HEPG2 cancer cell line (EC(50)=10.28
      MUg/mL for HEPG2 and EC(50)=10.79 MUM for FAK), which was comparable to the
      positive control. Docking simulation was performed to position compound 2p into
      the FAK structure active site to determine the probable binding model. The
      results of antiproliferative and Western-blot assay demonstrated that compound 2p
      possessed good antiproliferative activity against HEPG2 cancer cell line.
      Therefore, compound 2p with potent FAK inhibitory activity may be a potential
      anticancer agent against HEPG2 cancer cell.

PMID- 21889346
TI  - Training attentional control in infancy.
AB  - Several recent studies have reported that cognitive training in adults does not
      lead to generalized performance improvements [1, 2], whereas many studies with
      younger participants (children 4 years and older) have reported distal transfer
      [3, 4]. This is consistent with convergent evidence [5-8] for greater neural and
      behavioral plasticity earlier in development. We used gaze-contingent paradigms
      to train 11-month-old infants on a battery of attentional control tasks. Relative
      to an active control group, and following only a relatively short training
      period, posttraining assessments revealed improvements in cognitive control and
      sustained attention, reduced saccadic reaction times, and reduced latencies to
      disengage visual attention. Trend changes were also observed in spontaneous
      looking behavior during free play, but no change was found in working memory. The
      amount of training correlated with the degree of improvement on some measures.
      These findings are to our knowledge the first demonstration of distal transfer
      following attentional control training in infancy. Given the longitudinal
      relationships identified between early attentional control and learning in
      academic settings [9, 10], and the causal role that impaired control of attention
      may play in disrupting learning in several disorders [11-14], the current results
      open a number of avenues for future work.

PMID- 21889347
TI  - The intraoperative gap difference (flexion gap minus extension gap) is altered by
      insertion of the trial femoral component.
AB  - A Tensor/Balancer device has been recently developed in order to assess soft
      tissue balancing in total knee arthroplasty (TKA) under more physiological
      conditions. This device allows us to measure the joint gap with a trial femoral
      component in place with the patella reduced. The purpose of this study was to
      clarify whether the placement of the component changes the intraoperative gap
      difference (flexion gap distance minus extension gap distance). We prospectively
      investigated the extension (0 degrees ) and flexion (90 degrees ) gaps in 73
      posterior-stabilized TKAs under 30 lb of joint distraction force. Then, we
      compared the gap difference with and without the trial femoral component in
      place. Our results showed that the intraoperative gap difference with the trial
      femoral component in place was larger than the intraoperative gap difference
      without the trial component (p=0.00003; with the trial component: mean 4.7 mm
      (standard deviation (SD): 3.0mm); without the trial component: mean 2.7 mm (SD:
      3.3mm)). We consider that the change in gap difference with or without femoral
      component was caused by a relative difference in the elasticity and/or tightness
      of the soft tissue in extension versus flexion. Surgeons should be aware of this
      effect of the femoral component when considering intraoperative soft tissue
      balancing which leads to postoperative stability of the knee joint consequently.

PMID- 21889348
TI  - Synthesis, binding and cellular uptake properties of oligodeoxynucleotides
      containing cationic bicyclo-thymidine residues.
AB  - The synthesis and incorporation into oligodeoxynucleotides of two novel
      derivatives of bicyclothymidine carrying a cationic diaminopropyl or lysine unit
      in the C(6')-beta position is described. Compared to unmodified DNA these
      oligonucleotides show T(m)-neutral behavior when paired against complementary DNA
      and are destabilizing when paired against RNA. Unaided uptake experiments of a
      decamer containing five lys-bcT units into HeLa and HEK293T cells showed
      substantial internalization with mostly cytosolic distribution which was not
      observed in the case of an unmodified control oligonucleotide.

PMID- 21889349
TI  - Modeling the molecular basis for alpha4beta1 integrin antagonism.
AB  - We report a 3D QSAR study of almost 300 structurally diverse small molecule
      antagonists of the integrin alpha4beta1 whose biological activity spans six
      orders of magnitude. The alignment of the molecules was based on the conformation
      of a structurally related ligand bound to the alphaIIBbeta3 and alphavbeta3
      integrins in X-ray crystallographic studies. The molecular field method, CoMSIA,
      was used to generate the 3D QSAR models. The resulting models showed that the
      lipophilic properties were the most important, with hydrogen bond donor and
      steric properties less relevant. The models were highly significant (r(2)=0.89,
      q2(LOO)=0.67, r(2) (test set)=0.76), and could make robust predictions of the
      data (SEE=0.46, SEP=0.78, SEP (test set)=0.66). We predicted the antagonist
      activities of a further ten compounds with useful accuracy. The model appears
      capable of predicting alpha4beta1 integrin antagonist activity to within a factor
      of five for compounds within its domain of applicability. The implications for
      design of improved integrin antagonists will be discussed.

PMID- 21889350
TI  - Synthesis of new six- and seven-membered 1-N-iminosugars as promising glycosidase
      inhibitors.
AB  - New six- and seven-membered 1-N-iminosugars were prepared from d-glucose by the
      stereoselective Michael addition of nitromethane to d-glucose derived alpha,beta
      unsaturated ester A followed by one pot reduction of nitro/ester functionality
      and subsequent amine protection to get N-Cbz protected aminol 6. Hydrolysis of
      1,2-acetonide and reductive aminocyclization gave seven membered 1-N-iminosugar
      5b. While, hydrolysis of 1,2-acetonide followed by NaIO(4) oxidative cleavage and
      hydrogenation using 10% Pd(OH)(2)/C, H(2) gave six membered 1-N-iminosugar 4a;
      the hydrogenation using 10% Pd/C-H(2) however, gave N-methyl substituted 1-N
      iminosugar 4b. The hydrochloride salts of 4a/4b and 5b were found to be specific
      alpha-galactosidase and moderate alpha-glucosidae inhibitors, respectively, in
      micro molar range.

PMID- 21889351
TI  - The Phe105 loop of Alix Bro1 domain plays a key role in HIV-1 release.
AB  - Alix and cellular paralogs HD-PTP and Brox contain N-terminal Bro1 domains that
      bind ESCRT-III CHMP4. In contrast to HD-PTP and Brox, expression of the Bro1
      domain of Alix alleviates HIV-1 release defects that result from interrupted
      access to ESCRT. In an attempt to elucidate this functional discrepancy, we
      solved the crystal structures of the Bro1 domains of HD-PTP and Brox. They
      revealed typical "boomerang" folds they share with the Bro1 Alix domain. However,
      they each contain unique structural features that may be relevant to their
      specific function(s). In particular, phenylalanine residue in position 105
      (Phe105) of Alix belongs to a long loop that is unique to its Bro1 domain.
      Concurrently, mutation of Phe105 and surrounding residues at the tip of the loop
      compromise the function of Alix in HIV-1 budding without affecting its
      interactions with Gag or CHMP4. These studies identify a new functional
      determinant in the Bro1 domain of Alix.

PMID- 21889352
TI  - Ligand-dependent perturbation of the conformational ensemble for the GPCR beta2
      adrenergic receptor revealed by HDX.
AB  - Mechanism of G protein-coupled receptor (GPCR) activation and their modulation by
      functionally distinct ligands remains elusive. Using the technique of amide
      hydrogen/deuterium exchange coupled with mass spectrometry, we examined the
      ligand-induced changes in conformational states and stability within the beta-2
      adrenergic receptor (beta(2)AR). Differential HDX reveals ligand-specific
      alterations in the energy landscape of the receptor's conformational ensemble.
      The inverse agonists timolol and carazolol were found to be most stabilizing even
      compared with the antagonist alprenolol, notably in intracellular regions where G
      proteins are proposed to bind, while the agonist isoproterenol induced the
      largest degree of conformational mobility. The partial agonist clenbuterol
      displayed conformational effects found in both the inverse agonists and the
      agonist. This study highlights the regional plasticity of the receptor and
      characterizes unique conformations spanning the entire receptor sequence
      stabilized by functionally selective ligands, all of which differ from the
      profile for the apo receptor.

PMID- 21889353
TI  - Measurements of relative depth doses and Cerenkov light using a scintillating
      fiber-optic dosimeter with Co-60 radiotherapy source.
AB  - In this study, we fabricated a scintillating fiber-optic dosimeter, which
      consists of an organic scintillator and a plastic optical fiber, for radiotherapy
      dosimetry. To select an adequate kind and length of scintillator for gamma-rays
      generated from a Co-60 source, scintillating light from various kinds and lengths
      of organic scintillators is measured. Using a scintillating fiber-optic
      dosimeter, the gamma-rays generated from a Co-60 therapy unit are measured and
      relative doses are obtained according to the field size of the gamma-ray beam and
      the depth in a water phantom. Also, Cerenkov light generated by the interactions
      of primary or secondary electrons and the plastic optical fiber is measured with
      different field sizes and depths of a water phantom using a background optical
      fiber.

PMID- 21889354
TI  - Neuroprotective actions of estradiol revisited.
AB  - Results from animal experiments showing that estradiol is neuroprotective were
      challenged 10 years ago by findings indicating an increased risk of dementia and
      stroke in women over 65 years of age taking conjugated equine estrogens. Our
      understanding of the complex signaling of estradiol in neural cells has recently
      clarified the causes of this discrepancy. New data indicate that estradiol may
      lose its neuroprotective activity or even increase neural damage, a situation
      that depends on the duration of ovarian hormone deprivation and on age-associated
      modifications in the levels of other molecules that modulate estradiol action.
      These studies highlight the complex neuroprotective mechanisms of estradiol and
      suggest a window of opportunity during which effective hormonal therapy could
      promote brain function and cognition.

PMID- 21889357
TI  - Autophagy and cytokines.
AB  - Autophagy is a highly conserved homoeostatic mechanism for the lysosomal
      degradation of cytosolic constituents, including long-lived macromolecules,
      organelles and intracellular pathogens. Autophagosomes are formed in response to
      a number of environmental stimuli, including amino acid deprivation, but also by
      both host- and pathogen-derived molecules, including toll-like receptor ligands
      and cytokines. In particular, IFN-gamma, TNF-alpha, IL-1, IL-2, IL-6 and TGF-beta
      have been shown to induce autophagy, while IL-4, IL-10 and IL-13 are inhibitory.
      Moreover, autophagy can itself regulate the production and secretion of
      cytokines, including IL-1, IL-18, TNF-alpha, and Type I IFN. This review
      discusses the potentially pivotal roles of autophagy in the regulation of
      inflammation and the coordination of innate and adaptive immune responses.

PMID- 21889355
TI  - Androgen receptor-driven chromatin looping in prostate cancer.
AB  - The androgen receptor (AR) is important for prostate cancer development and
      progression. Genome-wide mapping of AR binding sites in prostate cancer has found
      that the majority of AR binding sites are located within non-promoter regions.
      These distal AR binding regions regulate AR target genes (e.g. UBE2C) involved in
      prostate cancer growth through chromatin looping. In addition to long-distance
      gene regulation, looping has been shown to induce spatial proximity of two genes
      otherwise located far away along the genomic sequence and the formation of double
      strand DNA breaks, resulting in aberrant gene fusions (e.g. TMPRSS2-ERG) that
      also contribute to prostate tumorigenesis. Elucidating the mechanisms of AR
      driven chromatin looping will increase our understanding of prostate
      carcinogenesis and may lead to the identification of new therapeutic targets.

PMID- 21889356
TI  - FKBP51 and FKBP52 in signaling and disease.
AB  - FKBP51 and FKBP52 are diverse regulators of steroid hormone receptor signaling,
      including receptor maturation, hormone binding and nuclear translocation.
      Although structurally similar, they are functionally divergent, which is largely
      attributed to differences in the FK1 domain and the proline-rich loop. FKBP51 and
      FKBP52 have emerged as likely contributors to a variety of hormone-dependent
      diseases, including stress-related diseases, immune function, reproductive
      functions and a variety of cancers. In addition, recent studies have implicated
      FKBP51 and FKBP52 in Alzheimer's disease and other protein aggregation disorders.
      This review summarizes our current understanding of FKBP51 and FKBP52
      interactions within the receptor-chaperone complex, their contributions to health
      and disease, and their potential as therapeutic targets for the treatment of
      these diseases.

PMID- 21889358
TI  - Lactobacilli and bifidobacteria induce differential interferon-beta profiles in
      dendritic cells.
AB  - The health promoting effects of probiotics are well-documented; however, current
      knowledge on immunostimulatory effects is based on data from a single strain or a
      limited selection of strains or species. Here, we compared the capacity of 27
      lactobacilli and 16 bifidobacteria strains to stimulate bone marrow-derived
      dendritic cells (DC). Most lactobacilli strains, including Lactobacillus
      acidophilus, Lactobacillus gasseri, Lactobacillus casei and Lactobacillus
      plantarum, induced strong IL-12 and TNF-alpha production and up-regulation of
      maturation markers. In contrast, all bifidobacteria and certain lactobacilli
      strains were low IL-12 and TNF-alpha inducers. IL-10 and IL-6 levels showed less
      variation and no correlation with IL-12 and TNF-alpha. DC matured by strong IL-12
      inducing strains also produced high levels of interferon (IFN)-beta. When
      combining two strains, low IL-12 inducers inhibited this IFN-beta production as
      well as IL-12 and Th1-skewing chemokines. The IFN-beta induction was mediated
      through c-Jun N-terminal kinase (JNK) irrespective of the stimulating strain. The
      inhibitory bacteria induced higher levels of the transcription factor c-Jun
      dimerization protein (JDP)-2, thereby counteracting the effect of JNK. Our data
      demonstrate that lactobacilli can be divided into two groups of bacteria
      featuring contrasting effects, while all bifidobacteria exhibit uniform effects.
      This underlines the importance of selecting the proper strain(s) for probiotic
      purposes.

PMID- 21889359
TI  - Sleep duration, sleep quality, and biomarkers of inflammation in a Taiwanese
      population.
AB  - PURPOSE: Short and long sleep duration and sleep quality are associated with
      health including all-cause mortality, cardiovascular disease, diabetes, and
      obesity. Inflammation may play a role in mediating these associations. METHODS:
      We examined associations between inflammation and self-reported sleep
      characteristics in 1020 respondents of the 2000 and 2006 Social Environment and
      Biomarkers of Aging Study, a nationally representative survey of Taiwanese adults
      ages 53 and over. Regression models were used to estimate cross-sectional
      relationships between inflammation (interleukin-6, C-reactive protein,
      fibrinogen, e-selectin, soluble intercellular adhesion molecule-1, albumin, and
      white blood cell count) and a modified Pittsburgh Sleep Quality Index, index
      subcomponents, and self-reported sleep duration. Change in inflammatory markers
      between 2000 and 2006 was also used to predict long or short sleep duration in
      2006. RESULTS: Inflammation was not related to the overall index of sleep
      quality. However, longer sleep (>8 hr) was associated with higher levels of
      inflammation. These associations remained after adjustment for waist
      circumference, self-reported health decline, diabetes, arthritis/rheumatism,
      heart disease, and depressive symptoms. Increases in inflammation between 2000
      and 2006 were associated with long but not short sleep duration in 2006 for
      several markers. CONCLUSIONS: Long sleep duration may be a marker of underlying
      inflammatory illness in older populations. Future studies should explore whether
      inflammation explains observed relationships between long sleep and mortality.

PMID- 21889360
TI  - Moderating effects of interactions between dietary intake and socioeconomic
      status on the prevalence of metabolic syndrome.
AB  - PURPOSE: The purpose of this study is to examine how nutrients can affect the
      relationship between the development of metabolic syndrome (MS) and socioeconomic
      factors. METHODS: This study was based on data obtained from the 2005 Korea
      National Health and Nutrition Examination Survey was conducted as a health survey
      of nationally representative samples of non-institutionalized Korean. The final
      sample was composed of 3146 people over 40 years of age. RESULTS: The
      relationship between the prevalence of MS and socioeconomic factors was
      associated with the consumption of nutrients. The slope of the graphs increased
      sequentially from the 1st quintile to 5th quintile of nutrient consumption.
      However, the directions of the 4th and 5th quintile were reversed from that of
      the 1st, 2nd, and 3rd quintile in reference to the horizontal axis. That is, the
      1st, 2nd, and 3rd quintiles indicate that higher household income was associated
      with lower prevalence of MS. However, the plots for the 4th and 5th quintile
      indicate that higher the household income was associated with higher the
      prevalence of MS. This tendency was shown in all the models that yielded
      statistically significant confirmation of moderating effects. CONCLUSIONS: The
      association between the prevalence of MS and different socioeconomic status
      varies according to the level of nutrient consumption.

PMID- 21889361
TI  - Comparison of different analysis techniques for the determination of muscle onset
      in individuals with patellofemoral pain syndrome.
AB  - To understand patellofemoral pain syndrome (PFPS), recent studies have focused on
      assessing the onset in the vastus medialis and vastus lateralis to determine
      whether there is a delay between these muscles' activation. However, the results
      of these studies are not in agreement, as some research shows that there is a
      delay in the VMO, while others do not show delay. It has been suggested that this
      discrepancies may be due to differences in the signal processing and analysis.
      For this reason, this study aimed to compare the three techniques used for onset
      determination - automatic detection, visual inspection and cross-correlation -
      and to verify whether these methods are able to detect PFPS. The surface
      electromyography evaluation procedure was conducted in 22 pain-free control
      individuals and 11 with PFPS diagnoses, during a stair climbing. The standard
      error of measurement (SEM) showed that cross-correlation presents the lower
      variation (2.56/3.27, control/PFPS) in relation to visual (3.77/10.19,
      control/PFPS) and automatic detection (43.23/51.98, control/PFPS, respectively).
      But when using the cross-correlation technique, we were not able to distinguish
      the groups (-6.56/-9.74ms, control/PFPS, p=0.15). Therefore, use of muscle onset
      may not be the best way to distinguish individuals with PFPS.

PMID- 21889362
TI  - Altered activity of the serratus anterior during unilateral arm elevation in
      patients with cervical disorders.
AB  - Altered activity in the axioscapular muscles is considered to be an important
      feature in patients with neck pain. The activity of the serratus anterior (SA)
      and trapezius muscles during arm elevation has not been investigated in these
      patients. The objectives of this study was to investigate whether there is a
      pattern of altered activity in the SA and trapezius in patients with insidious
      onset neck pain (IONP) (n=22) and whiplash associated disorders (WAD) (n=27). An
      asymptomatic group was selected for baseline measurements (n=23). Surface
      electromyography was used to measure the onset of muscle activation and duration
      of muscle activity of the SA as well as the upper, middle, and lower trapezius
      during unilateral arm elevation in the three subject groups. Both arms were
      tested. With no interaction, the main effect for the onset of muscle activation
      and duration of muscle activity for serratus anterior was statistically
      significant among the groups. Post hoc comparison revealed a significantly
      delayed onset of muscle activation and less duration of muscle activity in the
      IONP group, and in the WAD group compared to the asymptomatic group. There were
      no group main effects or interaction effects for upper, middle and lower
      trapezius. This finding may have implications for scapular stability in these
      patients because the altered activity in the SA may reflect inconsistent or
      poorly coordinated muscle activation that may reduce the quality of neuromuscular
      performance and induce an increased load on the cervical and the thoracic spine.

PMID- 21889363
TI  - sEMG activity of masticatory, neck, and trunk muscles during the treatment of
      scoliosis with functional braces. A longitudinal controlled study.
AB  - BACKGROUND: Studies on the relationship between occlusal problems and the spine
      are of increasing interest. In this study, we monitored the sEMG activity of
      masticatory, neck, and trunk muscles during the treatment of scoliosis in young
      patients, and compared the data with a control of untreated group. SUBJECTS AND
      METHODS: Twelve white Caucasian patients (nine males and three females; mean age
      of 8.0+/-1.5 years) with scoliosis and Class I occlusion (without crowding) were
      included in this study (study group). Fifteen healthy subjects (nine males and
      six females; mean age of 9.5+/-0.8 years) were recruited as control group. The
      subjects were visited before they underwent the treatment of scoliosis, as well
      as after 3 (T1) and 6 months (T2) of their treatment for scoliosis. The patients
      were instructed to wear the device during sleep and during the day, according to
      the protocol given by their orthopedic. RESULTS: The treated group showed
      statistically significant changes in the sEMG activity of masticatory, neck, and
      trunk muscles, both at rest and during MVC of the mandible with respect to T0.
      The masseter and the anterior temporalis showed a significant improvement in the
      asymmetry index from T0 to T2. On the other hand, subjects in the control group
      did not register much change. CONCLUSION: Our findings suggest that the use of a
      functional device for the treatment of scoliosis induces a significant reduction
      in the asymmetry index of the trunk muscles, as well as a significant increase in
      the contractility of masticatory muscles.

PMID- 21889364
TI  - Evaluation of tricuspid and pulmonary valves using epicardial and transesophageal
      echocardiography--a comparative study.
AB  - OBJECTIVE: To compare measurements obtained by transesophageal echocardiography
      (TEE) and epicardial echocardiography (EE) for evaluation of the tricuspid valve
      (TV) and pulmonary valve (PV). DESIGN: Prospective observational. SETTING:
      University hospital. PARTICIPANTS: Patients undergoing elective coronary artery
      bypass grafting with or without aortic valve replacement. INTERVENTIONS: After
      routine intraoperative TEE, EE was performed to compare measurements obtained by
      the 2 methods. MEASUREMENTS AND MAIN RESULTS: After institutional review board
      approval, 25 patients >18 years old were recruited. Biases with EE versus TEE for
      E and A waves were 11.9 cm/second (95% confidence interval [CI], 48.2 to -24.4)
      and 6.8 cm/second (95% CI, 28 to -15), respectively, and for E/A ratio was 0.08
      (95% CI, 1.2 to -1). Pulmonary velocity bias was 57.94 cm/second (95% CI, 192.9
      to -76.98), with higher values using EE. Bias for pulmonary trunk diameter was 
      0.31 cm (95% CI, 1.5 to -2.1). For quality of images, means were 2.4 (standard
      deviation [SD], 1.0) for EE and 2.3 (SD, 0.57) with TEE for TV and 2.4 (SD, 1.0)
      with EE and 2.5 (SD, 1.0) with TEE for PV. For the number of leaflets visualized,
      means were 2.2 (SD, 1.0) with EE and 2.5 (SD, 0.5) with TEE for TV and 2.5 (SD,
      0.5) for EE and 1.3 (SD, 1.1) with TEE for PV. CONCLUSIONS: There was good
      agreement for Doppler measurements across TVs; however, measurements across PVs
      were significantly higher with EE versus TEE. TV Doppler measurements were
      difficult to acquire even for surgeons experienced in epiaortic scanning.

PMID- 21889365
TI  - Pilot implementation of a perioperative protocol to guide operating room-to
      intensive care unit patient handoffs.
AB  - OBJECTIVES: Perioperative handoffs are a particularly high-risk period given
      patients' postprocedural physiology, their physical transport through the
      hospital, and the triad transfer of personnel, information, and technology. The
      authors piloted a new perioperative handoff process to guide patient transfers
      from the cardiac operating room (OR) to the cardiac surgical intensive care unit
      (CSICU). The aim of the study was to evaluate the impact of a standardized
      handoff process on patient care and provider satisfaction. DESIGN: A prospective,
      unblinded intervention study. SETTING: A CSICU in a teaching hospital.
      PARTICIPANTS: Two hundred thirty-eight health care practitioners during the
      transfer of care of 60 patients. INTERVENTIONS: The implementation of a
      standardized handoff protocol and checklist. MEASUREMENTS AND MAIN RESULTS: After
      the protocol's implementation, the presence of all handoff core team members at
      the bedside increased from 0% at baseline to 68% after intervention. The
      percentage of missed information in the surgery report decreased from 26% to 16%
      (p = 0.03), but the percentage of missed information in the anesthesia report
      showed no significant change (19% to 17%, p > 0.05). Handoff satisfaction scores
      among intensive care unit (ICU) nurses increased from 61% to 81%. On average, the
      duration of handoff increased by 1 minute. CONCLUSIONS: A standardized handoff
      protocol that guides the transfer of care from the OR team to the CSICU team can
      reduce the risk of missed information and improve satisfaction among
      perioperative providers.

PMID- 21889366
TI  - The effectiveness of therapeutic exercise for painful shoulder conditions: a meta
      analysis.
AB  - BACKGROUND: Shoulder pain is the third leading musculoskeletal complaint seen by
      general practitioners. Physical therapy is often the first line of intervention
      in this population; however, there is limited description of what constitutes
      effective physical therapy treatment. No study has examined the effectiveness of
      therapeutic exercise across all painful shoulder conditions. Our purpose was to
      examine the effectiveness of therapeutic exercise as an intervention across all
      pathoanatomic mechanisms of shoulder pain in terms of range of motion (ROM),
      pain, and function. METHODS: Medline via Ovid, CINAHL (Cumulative Index to
      Nursing and Allied Health Literature), and the Cochrane Central Register of
      Controlled Trials were searched from 1997 through March 2011. Randomized
      controlled trials comparing physical therapist-prescribed exercises against any
      other type of intervention were included. Articles were qualitatively evaluated
      by use of the Physiotherapy Evidence Database scale by 5 separate reviewers. Data
      from included studies were extracted and synthesized with respect to the primary
      outcomes of ROM, pain, and function. Individual effect sizes were calculated with
      a standard formula, and overall effect was calculated by use of random- and fixed
      effects models. RESULTS: We qualitatively reviewed 19 articles; 17 achieved the
      criterion of 6 or better on the Physiotherapy Evidence Database scale.
      Significant heterogeneity in reporting among included studies limited
      quantitative assessment. Overall, therapeutic exercise has a positive effect on
      pain and function above all other interventions. The findings for ROM were
      inconclusive. CONCLUSION: Therapeutic exercise is an effective intervention for
      the treatment of painful shoulder conditions; however, subsequent research is
      necessary for translation into clinical practice.

PMID- 21889367
TI  - Small interfering RNA targeting heat shock protein 70 enhances chemosensitivity
      in human bladder cancer cells.
AB  - OBJECTIVES: To evaluate the expression levels of heat shock protein 70 (HSP70) in
      human urothelial cancer of the bladder and to assess the therapeutic effects of
      treatment with small interfering RNA (siRNA) targeting HSP70 on human bladder
      cancer KoTCC-1 cells. MATERIALS AND METHODS: HSP70 expression in bladder cancer
      specimens obtained from 235 patients were evaluated by immunohistochemical
      staining. We then analyzed changes in the growth and chemosensitivity of KoTCC-1
      cells following treatment with HSP70 siRNA. RESULTS: Expression levels of HSP70
      protein in bladder cancer specimens were significantly related to major
      prognostic indicators, including pathologic stage and tumor grade. Treatment of
      KoTCC-1 with HSP70 siRNA resulted in a dose-dependent inhibition of HSP70
      expression. HSP70 siRNA significantly inhibited the growth of KoTCC-1 compared
      with that after treatment with scrambled control siRNA. Among several
      chemotherapeutic agents, the most powerful synergistic cytotoxic effect was
      observed when KoTCC-1 was treated with gemcitabine plus HSP70 siRNA, which
      induced more than 50% reduction in the IC50 of gemcitabine. Furthermore, a
      significant increase in the subG0-G1 fraction of KoTCC-1 and the DNA
      fragmentation was observed only after combined treatment with HSP70 siRNA and
      sublethal doses of gemcitabine, but not after treatment with either agent alone.
      Similarly, caspase-3 and caspase-9, but not caspase-8, in KoTCC-1 were
      synergistically activated by combined treatment with gemcitabine and HSP70 siRNA.
      CONCLUSIONS: Silencing of HSP70 expression using siRNA could be an attractive
      therapeutic strategy for bladder cancer by inducing inhibition of tumor growth as
      well as enhancing chemosensitivity.

PMID- 21889368
TI  - Age >= 80 years is independently associated with survival outcomes after radical
      cystectomy: results from the Canadian Bladder Cancer Network Database.
AB  - OBJECTIVES: The role of advanced age as an independent prognostic factor for
      clinical outcomes after radical cystectomy is controversial. The objective of the
      current study was to assess the associations between age and clinical outcomes in
      a large, multi-institutional series of patients treated with radical cystectomy
      for bladder cancer. MATERIALS AND METHODS: Institutional radical cystectomy
      databases containing detailed information on bladder cancer patients treated
      between 1993 and 2008 were obtained from 8 academic centers in Canada. Data were
      collected on 2,287 patients and combined into a relational database formatted
      with patient characteristics, pathologic characteristics, recurrence status, and
      survival status. Patient age was coded as <60 years, 60-69 years, 70-79 years, or
      >= 80 years. Clinical outcomes were 30-day mortality, 90-day mortality, overall
      survival (OS), disease-specific survival (DSS), and recurrence-free survival
      (RFS). Logistic regression and Cox proportional hazards regression analysis were
      used to analyze survival data. RESULTS: Five hundred fifty-seven (24.6%), 679
      (30.0%), 846 (37.4%), and 181 (8.0%) patients were <60 years, 60-69 years, 70-79
      years, and >= 80 years, respectively. Increased age was associated with decreased
      utilization rates of neoadjuvant chemotherapy (P = 0.0143), adjuvant chemotherapy
      (P < 0.0001), and continent urinary diversion (P < 0.0001) as well as advanced
      pathologic tumor stage (P = 0.0003), increased positive surgical margins (P <
      0.0001), and lymphovascular invasion (P = 0.0335). Compared with patients < 60
      years, multivariate regression analysis showed that age >= 80 years was
      independently associated with 90-day mortality (OR 2.98, 95% CI 1.22-7.30), OS
      (HR 2.03, 95% CI 1.51-2.75), DSS (HR 1.56, 95% CI 1.09-2.24), and RFS (HR 2.06,
      95% CI 1.57-2.70). CONCLUSIONS: Age >= 80 years at the time of radical cystectomy
      was independently associated with adverse survival outcomes. These data suggest
      that increased chronologic age should be considered in clinical trial design and
      in nomograms predicting survival.

PMID- 21889369
TI  - Multicentric retrospective study of endovascular treatment for restenosis after
      open carotid surgery.
AB  - OBJECTIVES: To analyse perioperative and midterm outcomes of carotid artery
      stenting (CAS) for symptomatic >50% and asymptomatic >70% restenosis after open
      carotid surgery (OCS). DESIGN: A multicentric retrospective study. METHODS:
      Outcome measures 30-day death, neurologic and anatomic (thrombosis, restenosis)
      events. Univariant and multivariant logistic regression analyses were performed
      to identify predictive factors for neurologic and anatomic events. RESULTS: A
      total of 249 patients with a mean age of 69 years (range, 45-88) were treated for
      asymptomatic (86%) or symptomatic (14%) restenosis. The 30-day combined operative
      mortality and stroke morbidity was 2.8% in asymptomatic patients and 2.9% in
      symptomatic patients. Events during follow-up (mean duration, 29 months) included
      stroke in four cases, TIA in two, stent thrombosis in four and restenosis in 21.
      Kaplan-Meier estimates of overall survival, neurologic-event-free survival,
      anatomic-event-free survival and reintervention-free survival were 95.4%, 94.7%,
      96.7% and 99.5%, respectively, at 1 year and 80.3%, 93.8%, 85.1% and 96%,
      respectively, at 4 years. Multivariant analysis showed that statin use was
      correlated with a lower risk of anatomic events (odds ratio (OR) = 0.15 (95%
      confidence interval (CI) 0.03-0.68), p = 0.01) and that bypass was associated
      with a higher risk of anatomic events than endarterectomy (OR = 5.0 (95% CI 1.6
      16.6), p = 0.009). CONCLUSION: CAS is a feasible therapeutic alternative to OCS
      for carotid restenosis with acceptable risks in the perioperative period.
      Restenosis rate may be higher in patients treated after bypass.

PMID- 21889370
TI  - Impact of aortic grafts on arterial pressure: a computational fluid dynamics
      study.
AB  - OBJECTIVE: Vascular prostheses currently used in vascular surgery do not have the
      same mechanical properties as human arteries. This computational study analyses
      the mechanisms by which grafts, placed in the ascending aorta (proximal) and
      descending aorta (distal), affect arterial blood pressure. METHODS: A one
      dimensional cardiovascular model was developed and adapted to include the graft
      geometry with in vitro measured mechanical properties. Pressure at the aortic
      root and haemodynamic parameters were computed and compared for a control,
      proximal and distal graft case. RESULTS: In comparison to the control case, the
      proximal graft increased characteristic impedance by 58% versus only 1% change
      for the distal graft. The proximal and distal graft increased pulse pressure by
      21% and 10%, respectively. CONCLUSIONS: The mechanisms underlying pulse pressure
      increase are different for proximal and distal grafts. For the proximal graft,
      the primary reason for pulse pressure rise is augmentation of the forward wave,
      resulting from characteristic impedance increase. For the distal graft, the pulse
      pressure rise is associated with augmented wave reflections resulting from
      compliance mismatch. Overall, the proximal aortic graft resulted in greater
      haemodynamic alterations than the distal graft. Thus, it is likely that patients
      who receive ascending aorta grafts are more prone to systolic hypertension and
      therefore deserve closer blood pressure monitoring.

PMID- 21889371
TI  - Infected Viabahn stent graft in the superficial femoral artery.
AB  - We present a case of an infected stent graft in the superficial femoral artery
      (SFA). A 67-year-old woman underwent excision of an infected Viabahn stent graft.
      At exploration there was no apparent artery around the majority of the stent
      graft, suggesting that the SFA had been autolysed. Infected stents and stent
      grafts are rare in the SFA position. The risk of infection is likely minimised
      with standard treatments including drainage of infection prior to stent graft
      placement and periprocedural antibiotic administration. Successful management
      will, in most cases, require excision of the stent graft and adjunctive arterial
      reconstruction, as necessary.

PMID- 21889373
TI  - Thoughts on the psychological component of TMJ/TMD syndrome.

PMID- 21889374
TI  - Gaucher disease type 2: homozygosity for the mutation F331S in two unrelated
      consanguineous Muslim Arab patients with Gaucher disease from the Gaza and Jenin
      regions.

PMID- 21889375
TI  - Does abnormal non-rapid eye movement sleep impair declarative memory
      consolidation?: Disturbed thalamic functions in sleep and memory processing.
AB  - Non-rapid eye movement (NREM) sleep has recently garnered support for its role in
      consolidating hippocampus-based declarative memories in humans. We provide a
      brief review of the latest research on NREM sleep activity and its association
      with declarative memory consolidation. Utilizing empirical findings from sleep
      studies on schizophrenia, Alzheimer's disease, and fibromyalgia, we argue that a
      significant reduction of slow-wave sleep and sleep spindle activity contribute to
      the development of deficits in declarative memory consolidation along with
      concomitant sleep disturbances commonly experienced in the aforementioned
      disorders. A tentative model is introduced to describe the mediating role of the
      thalamocortical network in disruptions of both declarative memory consolidation
      and NREM sleep. The hope is to stimulate new research in further investigating
      the intimate link between these two very important functions.

PMID- 21889376
TI  - Rotor-synchronized dipolar-filter sequence at fast MAS in solid-state NMR.
AB  - Dipolar filters are of considerable importance for eliminating the (1)H NMR
      signal of the rigid components of heterogeneous compounds while selecting the
      signal of their mobile parts. On the basis of such filters, structural and
      dynamical information of these compounds can often be acquired through further
      manipulations (e.g. spin diffusion) on the spin systems. To overcome the
      destructive interferences between the magic angle spinning (MAS) speed and the
      cycle-time of the widely-used Rotor-Asynchronized Dipolar Filter (RADF) sequence,
      we introduce a new method called Rotor-Synchronized Dipolar Filter (RSDF). This
      communication shows that this sequence does not present any interference with the
      spinning speed and is more compatible than RADF with high MAS frequencies
      (nu(R)>12 kHz). This new pulse sequence will potentially contribute to future
      researches on heterogeneous materials, such as multiphase polymer and membrane
      systems.

PMID- 21889377
TI  - The principle of reciprocity.
AB  - The circumstances surrounding the realisation that NMR signal reception could be
      quantified in a simple fundamental manner using Lorentz's Principle of
      Reciprocity are described. The poor signal-to-noise ratio of the first European
      superconducting magnet is identified as a major motivating factor, together with
      the author's need to understand phenomena at a basic level. A summary is then
      given of the thought processes leading to the very simple pseudo-static formula
      that has been the basis of signal-to-noise calculations for over a generation.

PMID- 21889378
TI  - Optimising time-varying gradient orientation for microstructure sensitivity in
      diffusion-weighted MR.
AB  - Here we investigate whether varying the diffusion-gradient orientation during a
      general waveform single pulsed-field gradient sequence improves sensitivity to
      the size of coherently oriented pores over having a fixed orientation. The
      experiment optimises the shape and the orientation of the gradient waveform in
      each of a set of measurements to minimise the expected variance of estimates of
      the parameters of a simple model. A key application motivating the work is
      measuring the size of axons in white matter. Thus, we use a two compartment white
      matter model with impermeable, single-radius cylinders, and search for waveforms
      that maximise the sensitivity to axon radius, intra-cellular volume fraction and
      diffusion constants. Output of the optimisation suggests the only benefit of
      allowing the gradient orientation to vary in the plane perpendicular to the
      cylinders is that we can gain perpendicular gradient strength by maximising two
      orthogonal gradients simultaneously. This suggests that varying orientation in
      itself does not increase the sensitivity to model parameters. On the other hand,
      the variation in a plane containing the parallel direction increases the
      sensitivity significantly because parallel sensitivity improves the diffusion
      constant estimates. However, we also find that similar improvement in the
      estimates can be achieved without optimising the orientation, but by having one
      measurement in the parallel and the rest in the perpendicular direction. The
      optimisation searches a very large space where it cannot hope to find the global
      minimum so we cannot make a categorical conclusion. However, given the
      consistency of the results in multiple reruns and variations of the experiments
      reported here, we can suggest that for probing coherently oriented systems, pulse
      sequences with variable orientation, such as double-wave vector sequences, do not
      offer more advantage than fixed orientation sequences with optimised shape. The
      advantage of varying orientation is however likely to emerge for more complex
      systems with dispersed pore orientation.

PMID- 21889379
TI  - Non-uniformity correction of human brain imaging at high field by RF field
      mapping of B1+ and B1-.
AB  - A new method of non-uniform image correction is proposed. Image non-uniformity is
      originated from the spatial distribution of RF transmission and reception fields,
      represented as B(1)(+) and B(1)(-), respectively. In our method, B(1)(+) mapping
      was performed invivo by a phase method. In B(1)(-) mapping, images with multiple
      TEs were acquired with a multi-echo adiabatic spin echo (MASE) sequence which
      enables homogeneous excitation. By T(2) fitting of these images an M(0) map
      (M(0)(MASE)) was obtained, in which signal intensity was expressed as the product
      of B(1)(-) and M0(1-e-(TR/T1)) . The ratio of this M(0)(MASE) map to the B(1)(+)
      map showed a similar spatial pattern in different human brains. These ratios of
      M(0)(MASE) to B(1)(+) in 24 subjects were averaged and then fitted with a
      spatially polynomial function to obtain a ratio map of B(1)(-)/B(1)(+)(alpha).
      Uniform image was achieved in spin echo (SE), MASE and inversion recovery
      turboFLASH (IRTF) images using measured B(1)(+) and calculated B(1)(-) by
      alphaB(1)(+). Water fractions in gray and white matters obtained from the M(0)
      images corrected by this method were in good agreement with previously reported
      values. From these experimental results, the proposed method of non-uniformity
      correction is validated at 4.7 T imaging.

PMID- 21889380
TI  - Recoupling in solid state NMR using gamma prepared states and phase matching.
AB  - The paper describes two-dimensional solid state NMR experiments that use powdered
      dephased antiphase coherence (gamma preparation) to encode chemical shifts in the
      indirect dimension. Both components of this chemical shift encoded gamma-prepared
      states can be refocused into inphase coherence by a recoupling element. This
      helps to achieve sensitivity enhancement in 2D NMR experiments by quadrature
      detection. The powder dependence of the gamma-prepared states allows for
      manipulating them by suitable insertion of delays in the recoupling periods. This
      helps to design experiments that suppress diagonal peaks in 2D spectra, leading
      to improved resolution. We describe some new phase modulated heteronuclear and
      homonuclear recoupling pulse sequences that simplify the implementation of the
      described experiments based on gamma prepared states. Recoupling in the
      heteronuclear spin system is achieved by matching the difference in the amplitude
      of the sine/cosine modulated phase on the two rf-channels to the spinning
      frequency while maintaining the same power on the two rf-channels.

PMID- 21889381
TI  - Site-specific phi- and psi-torsion angle determination in a uniformly/extensively
      13C- and 15N-labeled peptide.
AB  - A solid-state rotational-echo double resonance (REDOR) NMR method was introduced
      to identify the phi- and psi-torsion angle from a (1)H-(15)N or (1)H-(13)C' spin
      system of alanine-like residues in a selectively, uniformly, or extensively (15)N
      /(13)C-labeled peptide. When a C(alpha)(i) or a (15)N peak is site-specifically
      obtainable in the NMR spectrum of a uniformly (15)N/(13)C-labeled sample system,
      the psi- or phi-torsion angle specified by the conformational structure of
      peptide geometry involving (15)N(i)-(1)H(alpha)i-(15)N(i+1) or (13)C'(i-1)
      (1)H(N)i-(13)C'(i) spin system can be identified based on (13)C(alpha)- or (15)N
      detected (1)H(alpha)-(15)N or (1)H(N)-(13)C REDOR experiment. This method will
      conveniently be utilized to identify major secondary motifs, such as alpha-helix,
      beta-sheet, and beta-turn, from a uniformly (15)N-/(13)C-labled peptide sample
      system. When tested on a (13)C-/(15)N-labeled model system of a three amino acid
      peptide Gly-[U-(13)C, (15)N]Ala-[U-(13)C, (15)N]Leu, the psi-angle of alanine
      obtained experimentally, psi = -40 +/- 30 degrees , agreed reasonably well with
      the X-ray determined angle, psi = -39 degrees .

PMID- 21889382
TI  - Recollections of REDOR.
AB  - Rotational-echo, double-resonance NMR (REDOR) is an experiment designed to
      measure heteronuclear dipolar couplings in solids and is most often used to
      obtain structural details in solids. A brief history of its inception and
      development is presented.

PMID- 21889383
TI  - Platelet satellitism and dual surface immunoglobulin light-chain expression in
      circulating splenic marginal zone lymphoma cells.
AB  - Platelet satellitism is believed to be an in vitro phenomenon induced at room
      temperature in ethylenediamine tetraacetic acid-anticoagulated blood. Most
      reports involve neutrophils; involvement with circulating lymphoma cells are
      exceedingly rare. Normally, mature B cells exhibit allelic exclusion in which a
      single class of surface immunoglobulin light chains (either kappa or lambda) is
      expressed. The simultaneous expression of both kappa and lambda immunoglobulin
      light chains is rare. Herein, we report the unusual case of a patient with
      splenic marginal zone lymphoma in which circulating lymphoma cells express dual
      surface immunoglobulin light chains and exhibit platelet satellitism. In addition
      to clinical findings, a comprehensive analysis of the peripheral blood including
      correlated light and electron microscopy as well as flow cytometry are described.

PMID- 21889384
TI  - Therapeutic approaches to bone pathology in Gaucher disease: past, present and
      future.
AB  - Enzyme replacement therapy (ERT) is effective for the treatment of the systemic
      manifestations of Gaucher disease (GD) and can have a significant impact on
      skeletal manifestations. Bone involvement is broad and can occur in otherwise
      clinically asymptomatic individuals. The heterogeneity in GD-related bone disease
      may implicate multiple pathological processes such as disruption of coordinated
      bone cell activity, in addition to the physical impact of Gaucher cells causing
      vascular occlusion. Accumulated data suggests that earlier treatment initiation
      decreases skeletal complications and that bone disease may require a longer
      duration of treatment and higher dose than is necessary for organ involvement and
      hematopoietic manifestations. However, in some patients, bone manifestations
      persist and even worsen despite ERT, regardless of dose or duration of treatment.
      Treating skeletal disease should be considered of equal importance as treating
      visceral and hematologic manifestations. When treatment decisions involve
      multiple enzyme preparations and other therapeutic modalities such small
      molecules, the choice should be tailored on an individual basis with continuing
      evaluation.

PMID- 21889385
TI  - Atypical immunologic response in a patient with CRIM-negative Pompe disease.
AB  - We report the clinical course of a patient with severe infantile onset Pompe
      disease [cross-reactive immunologic material (CRIM) negative, R854X/R854X] who
      was diagnosed prenatally and received standard dosing of alglucosidase alfa
      (Myozyme(r)) enzyme replacement therapy (ERT) from day 10 of life until she
      passed away at the age of 3 years 9 months. In the immediate neonatal period
      there was cardiomegaly on chest X-ray, cardiac hypertrophy by echocardiogram, and
      development of a wide complex tachycardia. CRIM negative (CN) status was
      suspected based on her family history, and the available data at the time
      indicated that CN patients had limited survival even with ERT. However, given the
      opportunity for very early treatment, the treating provider and family elected to
      initiate treatment with ERT, without immune modulation. By 9 months of age
      echocardiogram was normal. Early motor development was within normal limits but
      by 2 years of age her developmental progress had slowed. She seroconverted by the
      4th month of ERT, and anti-rhGAA antibody titers peaked at 25,600 in the 27th
      month. Immunomodulatory therapy was considered but declined by family. She
      acquired Influenza A at 2 years 6 months, which led to a prolonged
      hospitalization with invasive respiratory support, and placement of tracheostomy
      and gastrostomy tube. Her developmental progress ceased, and she died suddenly at
      home from a presumed cardiac event at age 3 years 9 months. The poor outcomes
      observed in CN patients have been attributed to the development of high sustained
      antibody titers. Although this CN patient's anti-rhGAA response was elevated and
      sustained, it is unlike any of the 3 patterns that have been previously
      described: high titer CN, high titer CRIM positive (HTCP), and low titer CP
      (LTCP) patients. This patient's clinical course, with achievement of 24 months of
      motor gains, 30 months of ventilator-free survival and 45 month survival, is like
      that of only a fraction of ERT treated CN patients, yet it is identical to other
      reported CN patients in its relentless progression and early fatality. The
      immunologic response (moderate sustained antibody titers) described here has not
      been previously reported and may have played a role in the overall pattern of
      developmental decline. In light of proposed universal newborn screening for Pompe
      disease, there is an urgent need for improved understanding of the interplay
      between immunologic responses to the only available treatment, ERT, and the
      relentless nature of this disease in CN patients.

PMID- 21889386
TI  - Clinical outcome following pneumonectomy for management of chronic pyothorax in
      four cats.
AB  - Pneumonectomy is the resection of all lung lobes from one side of the thorax. The
      clinical findings, treatment and outcome of four cases of feline chronic
      pyothorax managed with exploratory thoracotomy and pneumonectomy are reported.
      All cases were initially medically managed with thoracic drain placement and
      antibiosis. However, resolution was not achieved with medical therapy and
      diagnostic imaging findings consistent with an area of abscessation or marked
      lung lobe consolidation were identified, supporting a decision for surgical
      management. Surgical exploration was performed via median sternotomy and, on the
      basis of gross inspection, non-functional lung was removed. A left-sided
      pneumonectomy was performed in three cats and a right-sided pneumonectomy in one.
      All cases survived to discharge and an excellent quality of life was reported on
      long-term follow-up. Pneumonectomy appears to be well tolerated in the cat.

PMID- 21889387
TI  - [Patient identification errors].

PMID- 21889388
TI  - Telemedicine and diabetes: achievements and prospects.
AB  - Health authorities currently have high expectations for telemedicine (TM), as it
      addresses several major challenges: to improve access to healthcare (especially
      for patients in underserved or remote areas); to overcome the scarcity of
      specialists faced with epidemic disease; and to reduce the costs of healthcare
      while improving quality. The aims of TM in the field of diabetes differ according
      to the type of diabetes. In type 1 diabetes (T1DM) associated with complex
      insulin regimens, the goal of TM is to help patients achieve better control of
      their blood glucose levels through accurate adjustment of insulin doses. In type
      2 diabetes (T2DM), while therapeutic adjustments may be necessary, improvement in
      blood glucose control is based primarily on behavioural changes (reduced calorie
      and carbohydrate intakes, increased physical activity). Many TM studies focusing
      on management of blood glucose levels have been published, but most failed to
      demonstrate any superiority of TM vs traditional care. While previously published
      meta-analyses have shown a slight advantage at best for TM, these meta-analyses
      included a mix of studies of varying durations and different populations (both
      T1DM and T2DM patients, adults and children), and tested systems of inconsistent
      quality. Studies published to date on TM suggest two currently promising
      approaches. First, handheld communicating devices, such as smartphones, loaded
      with software to apply physicians' prescriptions, have been shown to improve
      glycaemic control. These systems provide immediate assistance to the patient
      (such as insulin-dose calculation and food choice optimization at meals), and all
      data stored in the smartphone can be transmitted to authorized caregivers,
      enabling remote monitoring and even teleconsultation. These systems, initially
      developed for T1DM, appear to offer many possibilities for T2DM, too. Second,
      systems combining an interactive Internet system (or a mobile phone coupled to a
      remote server) with a system of communication between the healthcare provider and
      the patient by e-mail, texting or phone calls have also shown certain benefits
      for glycaemic control. These systems, primarily aimed at T2DM patients, generally
      provide motivational support as well. Although the individual benefits of these
      systems for glycaemic control are fewer than with smartphones, their widespread
      use should be of particular value for overcoming the relative shortage of doctors
      and reducing the health costs associated with a disease of such epidemic
      proportions.

PMID- 21889389
TI  - Fractal and nonlinear changes in the long-term baseline fluctuations of fetal
      heart rate.
AB  - The interpretation of heart rate patterns obtained by fetal monitoring relies on
      the definition of a baseline, which is considered as the running average heart
      rate in the absence of external stimuli during periods of fetal rest. We present
      a study along gestation of the baseline's fluctuations, in relation to fractal
      and nonlinear properties, to assess these fluctuations according with time
      varying attracting levels introduced by maturing regulatory mechanisms. A low
      risk pregnancy was studied weekly from the 17th to 38th week of gestation during
      long-term recording sessions at night (>6 h). Fetal averaged pulse rate samples
      and corresponding baseline series were obtained from raw abdominal ECG ambulatory
      data. The fractal properties of these series were evaluated by applying detrended
      fluctuation analysis. The baseline series were also explored to evaluate
      nonlinear properties and time ordering by applying the scaling magnitude and sign
      analyses. Our main findings are that the baseline shows fractal and even
      nonlinear anticorrelated fluctuations. This condition was specially the case
      before mid-gestation, as revealed by alpha values near to unit, yet becoming
      significantly more complex after 30 weeks of gestation as indicated by alpha(mag)
      values >0.5. The structured (i.e. not random) fluctuations and particular
      nonlinear changes that we found thus suggest that the baseline provides on itself
      information concerning the functional integration of cardiac regulatory
      mechanisms.

PMID- 21889390
TI  - Associations between availability of facilities within three different
      neighbourhood buffer sizes and objectively assessed physical activity in
      adolescents.
AB  - This study aims to explore whether objectively measured availability of parks and
      sports facilities within three different buffer sizes are associated with
      moderate-to-vigorous physical activity (MVPA) among adolescents, and to identify
      potential cognitive mediators of this association. Data were obtained from
      adolescents (N=209, mean age: 14.5 (SD: 0.6) years) at the follow-up measurement
      of the Children Living in Active Neighbourhoods study in 2004. MVPA was measured
      using accelerometers. Availability of parks and sport facilities were measured
      within 400, 800 and 2000 m buffers around participants' residential homes.
      Potential mediators (self-efficacy, attitude and the perceived availability of
      parks and sports grounds) were measured by self-administered questionnaires. No
      direct association was found between the objectively measured availability of
      facilities and objective assessments of MVPA and no evidence for mediation by
      cognitions was found in any of the buffer sizes. More specific and sensitive
      measures may be needed to understand environmental correlates of MVPA.

PMID- 21889391
TI  - A unified framework for inhibitory control.
AB  - Inhibiting unwanted thoughts, actions and emotions figures centrally in daily
      life, and the prefrontal cortex (PFC) is widely viewed as a source of this
      inhibitory control. We argue that the function of the PFC is best understood in
      terms of representing and actively maintaining abstract information, such as
      goals, which produces two types of inhibitory effects on other brain regions.
      Inhibition of some subcortical regions takes a directed global form, with
      prefrontal regions providing contextual information relevant to when to inhibit
      all processing in a region. Inhibition within neocortical (and some subcortical)
      regions takes an indirect competitive form, with prefrontal regions providing
      excitation of goal-relevant options. These distinctions are crucial for
      understanding the mechanisms of inhibition and how they can be impaired or
      improved.

PMID- 21889393
TI  - A comparative study on the aggregate formation of two oxazine dyes in aqueous and
      aqueous urea solutions.
AB  - The visible absorption spectra of two oxazine dyes, brilliant cresyl blue and
      nile blue, in aqueous and aqueous urea solutions (0.01-1 M) were studied as a
      function of the dye concentration. Due to structural similarity of the
      investigated dyes, their spectral features were compared. The dimerization
      behavior of the dyes in water with or without urea was analyzed in terms of
      monomer-dimer equilibrium. The nature and structure of the interacting pairs for
      these dyes were discussed using the exciton theory. The dimerization constant
      values of the dyes in aqueous and aqueous urea solutions were calculated. For
      both the dyes in aqueous urea solutions, a reduction in dimer formation was
      observed. The excitonic parameters were compared with those of oxazine-1, which
      is structurally similar to the investigated dyes.

PMID- 21889392
TI  - Serum biomarkers as potential predictors of antitumor activity of cetuximab
      containing therapy for locally advanced head and neck cancer.
AB  - We sought to identify biomarkers of antitumor activity in patients with locally
      advanced head and neck cancer treated with therapy containing cetuximab, an
      epidermal growth factor receptor (EGFR) inhibitor. Patients with stage III-IVB
      head and neck cancer received cisplatin, docetaxel, and cetuximab (TPE) followed
      by radiotherapy, cisplatin, and cetuximab (XPE) and maintenance cetuximab in a
      phase II clinical trial. Serum and tissue biomarkers were examined for treatment
      related changes and for association with clinical outcomes. Concentrations of 31
      cytokines, chemokines and growth factors were measured before and after 3 cycles
      (9 weeks) of induction TPE using multi-analyte immunobead-based profiling
      (Luminex Corp., Austin, TX), with selected analytes validated by a single analyte
      enzyme-linked immunosorbent assay. Tumor biomarkers included phosphorylated
      signal transducer and activator of transcription-3 (pSTAT3), EGFR and human
      papillomavirus (HPV). Thirty-one patients had baseline biomarkers and 25 had
      paired samples, pre- and post-TPE. Adjusting for false discovery, 14 analytes
      including MCP1c, IP-10, Leptin, interleukin (IL)-5, Eotaxin, IL-6, G-CSF, CXCL5
      changed significantly post TPE induction. Serum vascular endothelial growth
      factor (VEGF) and IL-6 levels were associated with tumor response as assessed by
      positron emission tomography and progression-free survival, however, the
      association was not significant after adjustment for false discovery. Analytes
      were not associated with toxicities, smoking history, HPV status, EGFR
      amplification, or pSTAT3 tumor protein levels. Baseline serum biomarkers, in
      particular VEGF and IL-6, were identified as potentially useful prognostic
      markers of cetuximab-containing therapy. Validation is warranted in future
      studies specifically designed to detect biomarker associations.

PMID- 21889394
TI  - Vibrational spectroscopic analysis of taranakite (K,NH4)Al3(PO4)3(OH).9(H2O) from
      the Jenolan Caves, Australia.
AB  - Many phosphate containing minerals are found in the Jenolan Caves. Such minerals
      are formed by the reaction of bat guano and clays from the caves. Among these
      cave minerals is the mineral taranakite (K,NH(4))Al(3)(PO(4))(3)(OH).9(H(2)O)
      which has been identified by X-ray diffraction. Jenolan Caves taranakite has been
      characterised by Raman spectroscopy. Raman and infrared bands are assigned to
      H(2)PO(4), OH and NH stretching vibrations. By using a combination of XRD and
      Raman spectroscopy, the existence of taranakite in the caves has been proven.

PMID- 21889395
TI  - Crimean-Congo hemorrhagic fever serosurvey in at-risk professionals, Madagascar,
      2008 and 2009.
AB  - BACKGROUND: Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic arboviral
      infection with hemorrhagic manifestation and often a fatal ending. Human become
      infected mainly through tick bite or by crushing infected tick, by contact with
      blood or tissues from viraemic livestock or patient. CCHF virus (CCHFV) has been
      isolated once in Madagascar but data on the epidemiology of the disease in the
      country are very scarce. OBJECTIVES: To investigate the circulation and the
      geographic distribution of CCHFV infection among at risk population in
      Madagascar. STUDY DESIGN: A national cross-sectional serologic survey was
      performed in 2008-2009 among slaughterhouse workers. RESULTS: A total of 1995
      workers were included. A recent CCHFV infection was detected in 1 of the 1995
      participants (0.50/00; 95% confidence interval [CI]: 0-0.15%), and a past CCHFV
      infection was detected in 15 participants (0.75%; 95% CI: 0.37-1.13%).
      CONCLUSION: Overall, the percentage of CCHFV infection seen in Madagascar among
      at-risk professionals is very low compared to endemic countries. An assessment of
      the prevalence in livestock as a sensitive indicator of CCHFV activity must be
      considered in order to confirm the lack or the weak endemicity of CCHF in
      Madagascar.

PMID- 21889396
TI  - Foveal and parafoveal spatial attention and its impact on the processing of
      facial expression: an ERP study.
AB  - OBJECTIVE: The aim was to investigate the effects of spatial attention, stimulus
      location, and emotional expression on the processing of face stimuli. METHODS:
      Healthy volunteers performed two sustained attention tasks, focusing their
      attention on either fixation (foveal location) or on a location several degrees
      above fixation (parafoveal location). Photographs of faces with either a neutral
      or a fearful expression were presented randomly at one of these locations. Event
      related potentials were recorded in response to the face stimuli. RESULTS:
      Spatial attention modulated the early P1 and N1 components for both foveally and
      parafoveally presented stimuli. Emotional expression effects already occurred at
      the P1 stage in response to attended foveal stimuli, but only arose from 220ms
      post-stimulus onwards in response to attended parafoveal stimuli. When faces were
      unattended, emotional expression effects were still present for parafoveal
      stimuli, whereas they were completely absent for foveal stimuli. CONCLUSIONS: The
      modulations of the P1/N1 components by fearful faces are due to an early sensory
      modulation of extrastriate generators, and reflect an enhanced allocation of
      attention to threat-related stimuli. SIGNIFICANCE: Future studies should take
      into account the possibility that spatial attention effects and effects of
      emotional expression processing are different for different positions in the
      visual field.

PMID- 21889397
TI  - Reference values for voluntary and stimulated single-fibre EMG using concentric
      needle electrodes: a multicentre prospective study.
AB  - OBJECTIVE: The aim of this study is to establish reference values for single
      fibre electromyography (SFEMG) using concentric needles in a prospective,
      multicentre study. METHODS: Voluntary or stimulated SFEMG at the extensor
      digitorum communis (EDC) or frontalis (FRO) muscles was conducted in 56-63 of a
      total of 69 normal subjects below the age of 60years at six Japanese institutes.
      The cut-off values for mean consecutive difference (MCD) of individual potentials
      were calculated using +2.5 SD or 95% prediction limit (one-tail) of the upper
      10th percentile MCD value for individual subjects. RESULTS: The cut-off values
      for individual MCD (+2.5 SD) were 56.8MUs for EDC-V (voluntary SFEMG for EDC),
      58.8MUs for EDC-S (stimulated SFEMG for EDC), 56.8MUs for FRO-V (voluntary SFEMG
      for FRO) and 51.0MUs for FRO-S (stimulated SFEMG for FRO). The false positive
      rates using these cut-off values were around 2%. CONCLUSIONS: The +2.5 SD and 95%
      prediction limit might be two optimal cut-off values, depending on the clinical
      question. The obtained reference values were larger than those reported
      previously using concentric needles, but might better coincide with conventional
      values. SIGNIFICANCE: This is the first multicentre study reporting reference
      values for SFEMG using concentric needles. The way to determine cut-off values
      and the statistically correct definition of the percentile were discussed.

PMID- 21889398
TI  - Tonic pain and continuous EEG: prediction of subjective pain perception by alpha
      1 power during stimulation and at rest.
AB  - OBJECTIVE: Pain neurophysiology has been chiefly characterized via event-related
      potentials (ERPs), which are exerted using brief, phase-locked noxious stimuli.
      Striving for objectively characterizing clinical pain states using more natural,
      prolonged stimuli, tonic pain has been recently associated with the individual
      peak frequency of alpha oscillations. This finding encouraged us to explore
      whether alpha power, reflecting the magnitude of the synchronized activity within
      this frequency range, will demonstrate a corresponding relationship with
      subjective perception of tonic pain. METHODS: Five-minute-long continuous EEG was
      recorded in 18 healthy volunteers under: (i) resting-state; (ii) innocuous
      temperature; and (iii) psychophysically-anchored noxious temperature. Numerical
      pain scores (NPSs) collected during the application of tonic noxious stimuli were
      tested for correlation with alpha-1 and alpha-2 power. RESULTS: NPSs and alpha
      power remained stable throughout the recording conditions (Ps?0.381). In the
      noxious condition, alpha-1 power obtained at the bilateral temporal scalp was
      negatively correlated with NPSs (Ps?0.04). Additionally, resting-state alpha-1
      power recorded at the bilateral temporal scalp was negatively correlated with
      NPSs reported during the noxious condition (Ps?0.038). CONCLUSIONS: Current
      findings suggest alpha-1 power may serve as a direct, objective and
      experimentally stable measure of subjective perception of tonic pain.
      Furthermore, resting-state alpha-1 power might reflect individuals' inherent
      tonic pain responsiveness. SIGNIFICANCE: The relevance of alpha-1 power to tonic
      pain perception may deepen the understanding of the mechanisms underlying the
      processing of prolonged noxious stimulation.

PMID- 21889399
TI  - Antimicrobial activity of the surface coatings on TiAlZr implant biomaterial.
AB  - This study is devoted to antimicrobial activity of new surface coatings on
      TiAlZr. Ti alloys such as TiAlZr are used as implant biomaterials, but, despite
      the good behavior of such alloys in simulated conditions, bacterial infections
      appear after the introduction of an implant into the body. The infections are
      typically caused by the adherence and colonization of bacteria on the surfaces of
      the implants. The study presents preparation and surface morphology
      characterization of coatings obtained via anodizing, as well as biomimetic
      coatings with hydroxyapatite and silver ions with and without antibiotic. The
      percentage inhibition of Escherichia coli bacteria growth was evaluated for each
      of the studied coating, and a Trojan-horse model of silver nanoparticles (nAg)
      antibacterial activity at interface was proposed. Such coatings could be more
      important taking into account that antibacterial treatments with antibiotics are
      becoming less effective due to their intensive use.

PMID- 21889400
TI  - Antioxidant properties of rare sugar D-allose: Effects on mitochondrial reactive
      oxygen species production in Neuro2A cells.
AB  - The anti-oxidative activity of the rare sugar D-allose has recently been
      reported, but the mechanism is largely unclear. In this study, we evaluated the
      reactive oxygen species (ROS) scavenging activities of D-allose and then examined
      the effects of D-allose on ROS production in mitochondria to clarify the
      antioxidant properties of D-allose. While D-allose did not scavenge hydrogen
      peroxide and superoxide anions, it eliminated hydroxyl radicals to the same
      extent as D-glucose. Rotenone, an uncoupler of mitochondrial respiratory complex
      I, induces ROS production in mouse neuroblastoma Neuro2A cells in the presence of
      D-glucose. However, in the presence of D-allose, there was no change in the ROS
      levels in Neuro2A cells following rotenone treatment. Furthermore, treatment with
      D-allose attenuated the D-glucose-dependent ROS generation induced by rotenone.
      Whereas treatment with D-glucose enhanced ATP synthesis in Neuro2A cells, D
      allose was less effective in producing intracellular ATP than D-glucose.
      Treatment with D-allose inhibited the ATP synthesis stimulated by D-glucose.
      These results suggest that D-allose suppresses ROS production in the mitochondria
      due to competition with D-glucose at the cellular level.

PMID- 21889401
TI  - Lipase-catalyzed process in an anhydrous medium with enzyme reutilization to
      produce biodiesel with low acid value.
AB  - One major problem in the lipase-catalyzed production of biodiesel or fatty acid
      methyl esters (FAME) is the high acidity of the product, mainly caused by water
      presence, which produces parallel hydrolysis and esterification reactions instead
      of transesterification to FAME. Therefore, the use of reaction medium in absence
      of water (anhydrous medium) was investigated in a lipase-catalyzed process to
      improve FAME yield and final product quality. FAME production catalyzed by
      Novozym 435 was carried out using waste frying oil (WFO) as raw material,
      methanol as acyl acceptor, and 3A molecular sieves to extract the water. The
      anhydrous conditions allowed the esterification of free fatty acids (FFA) from
      feedstock at the initial reaction time. However, after the initial esterification
      process, water absence avoided the consecutives reactions of hydrolysis and
      esterification, producing FAME mainly by transesterification. Using this
      anhydrous medium, a decreasing in both the acid value and the diglycerides
      content in the product were observed, simultaneously improving FAME yield. Enzyme
      reuse in the anhydrous medium was also studied. The use of the moderate polar
      solvent tert-butanol as a co-solvent led to a stable catalysis using Novozym 435
      even after 17 successive cycles of FAME production under anhydrous conditions.
      These results indicate that a lipase-catalyzed process in an anhydrous medium
      coupled with enzyme reuse would be suitable for biodiesel production, promoting
      the use of oils of different origin as raw materials.

PMID- 21889402
TI  - Development of a suction device for stabilizing in vivo real-time imaging of
      murine tissues.
AB  - In vivo real-time imaging of molecular or cellular dynamics in tissues in live
      animals is difficult due to their physiological movements. In this study, we
      propose a suction device for stabilizing live imaging, which was used to
      demonstrate fluorescence detection of circulating blood cells in vessels of mouse
      livers.

PMID- 21889403
TI  - Indoor environment and children's health: recent developments in chemical,
      biological, physical and social aspects.
AB  - Much research is being carried out into indoor exposure to harmful agents. This
      review focused on the impact on children's health, taking a broad approach to the
      indoor environment and including chemical, microbial, physical and social
      aspects. Papers published from 2006 onwards were reviewed, with regards to
      scientific context. Most of publications dealt with chemical exposure. Apart from
      the ongoing issue of combustion by-products, most of these papers concerned semi
      volatile organic compounds (such as phthalates). These may be associated with
      neurotoxic, reprotoxic or respiratory effects and may, therefore, be of
      particular interest so far as children are concerned. In a lesser extent,
      volatile organic compounds (such as aldehydes) that have mainly respiratory
      effects are still studied. Assessing exposure to metals is still of concern, with
      increasing interest in bioaccessibility. Most of the papers on microbial exposure
      focused on respiratory tract infections, especially asthma linked to allergens
      and bio-aerosols. Physical exposure includes noise and electromagnetic fields,
      and articles dealt with the auditory and non auditory effects of noise. Articles
      on radiofrequency electromagnetic fields mainly concerned questions about non
      thermal effects and papers on extremely low-frequency magnetic fields focused on
      the characterization of exposure. The impact of the indoor environment on
      children's health cannot be assessed merely by considering the effect of these
      different types of exposure: this review highlights new findings and also
      discusses the interactions between agents in indoor environments and also with
      social aspects.

PMID- 21889404
TI  - Anatomical organization of antennal-lobe glomeruli in males and females of the
      scarab beetle Holotrichia diomphalia (Coleoptera: Melolonthidae).
AB  - The glomerular organization of the primary olfactory brain center, the antennal
      lobe, was studied in males and females of Holotrichia diomphalia adults using
      serial histological sections labeled by the reduced silver-stain technique. The
      results revealed an apparent sexual dimorphism. Whereas an enlarged cap-shaped
      glomerulus was found at the antennal nerve entrance into the antennal lobe in
      males, no such unit was present in females. Also the size of the antennal lobe
      differed between the sexes, the antennal lobe of males being larger than that of
      females. We estimated the total number of glomeruli at approximately 60 units in
      the female antennal lobe. In males, we could discriminate only those glomeruli
      that were located in the anterior area of the antennal lobe.

PMID- 21889405
TI  - Origin, phenotype and function of human natural killer cells in pregnancy.
AB  - During the early phases of pregnancy, natural killer (NK) cells are the
      predominant lymphoid cells in the human decidua. Here, rather than act as killers
      and/or drivers of inflammation, NK cells contribute to tissue building and
      remodeling and formation of new vessels due to the release of interleukin-8,
      vascular endothelial growth factor, stromal cell-derived factor-1 and interferon
      gamma-inducible protein-10. Here, we propose that the interaction of NK cells
      with CD14(+) myelomonocytic cells to promote induction of T regulatory cells
      plays a pivotal role in immunosuppression and tolerance towards the fetus
      allograft. Importantly, CD34(+) hematopoietic precursors are present in human
      decidua and may give rise to decidual NK cells. Defects in decidual NK cell
      generation, or in appropriate functional interactions with other cell types,
      could have major consequences for successful pregnancy.

PMID- 21889406
TI  - Endoplasmic reticulum stress, obesity and diabetes.
AB  - The endoplasmic reticulum (ER) stress response, also commonly known as the
      unfolded protein response (UPR), is an adaptive response used to align ER
      functional capacity with demand. It is activated in various tissues under
      conditions related to obesity and type 2 diabetes. Hypothalamic ER stress
      contributes to inflammation and leptin/insulin resistance. Hepatic ER stress
      contributes to the development of steatosis and insulin resistance, and
      components of the UPR regulate liver lipid metabolism. ER stress in enlarged fat
      tissues induces inflammation and modifies adipokine secretion, and saturated fats
      cause ER stress in muscle. Finally, prolonged ER stress impairs insulin synthesis
      and causes pancreatic beta cell apoptosis. In this review, we discuss ways in
      which ER stress operates as a common molecular pathway in the pathogenesis of
      obesity and diabetes.

PMID- 21889407
TI  - Potential benefits of plasma exchange by apheresis on the treatment of severe
      Icteric Leptospirosis: case report and literature review.
AB  - The role of plasmapheresis on the treatment of Leptospirosis has not been define,
      although it has already been used with beneficial effects in the reported case
      mentioned above, where was possible to contribute to the resolution of the toxic
      effects on the tubular renal cells. This case report show how plasma exchange
      prevents the multiorganic failure.

PMID- 21889408
TI  - High frequency of autoimmunization among transfusion-dependent Tunisian
      thalassaemia patients.
AB  - BACKGROUND: Limited data are available on the frequency of RBC alloimmunization
      and autoimmunization in transfusion-dependent Tunisian beta thalassaemia
      patients. MATERIALS AND METHODS: We analyzed the clinical and transfusion records
      of 130 patients (57 females and 73 males; mean age 119 months; range 12-11
      months) with beta thalassaemia major and who had regular blood transfusions for
      periods ranging from 12 to 311 months. RESULTS: Of the 130 patients, ten (7.7%)
      developed RBC alloantibodies. The most common alloantibodies were directed
      against antigens in the Rh systems. Erythrocyte-autoantibodies as determined by a
      positive direct antiglobulin Coombs test, developed in 52(40%) patients with and
      without underlying RBC alloantibodies, thereby causing autoimmune haemolytic
      anaemia in eleven patients (21%). CONCLUSIONS: Autoimmunization to erythrocyte
      antigens is a frequent complication in patients with beta thalassaemia major.
      Several factors might have contributed to the high autoimmunization rate observed
      in this study, including non phenotypic blood exposure and alloantibody formation
      prior to positive Coombs test.

PMID- 21889409
TI  - What is a fair comparison in head-to-head trials of antiepileptic drugs?

PMID- 21889411
TI  - Idiopathic macro-orchidism with testicular lobulation in an adolescent.
AB  - Marked testicular enlargement in the pediatric age group can be caused by many
      different conditions and is rarely idiopathic. Ultrasound is the primary imaging
      modality for evaluation of such cases. Bilateral asymmetric idiopathic macro
      orchidism with diffuse testicular lobulations is a condition which has not been
      described before in the literature. We report the clinical, sonographic and
      histological features of this unusual combination in an adolescent boy.

PMID- 21889410
TI  - Efficacy and safety of pregabalin versus lamotrigine in patients with newly
      diagnosed partial seizures: a phase 3, double-blind, randomised, parallel-group
      trial.
AB  - BACKGROUND: Efficacious and safe monotherapy options are needed for adult
      patients with newly diagnosed epilepsy. As an adjunctive treatment for partial
      seizures, pregabalin compares favourably with lamotrigine and is an effective,
      approved treatment. We studied the efficacy and safety of pregabalin as
      monotherapy, using a design that complied with European regulatory requirements
      and International League Against Epilepsy guidelines. METHODS: This phase 3,
      double-blind, randomised, non-inferiority study compared the efficacy and
      tolerability of pregabalin and lamotrigine monotherapy in patients with newly
      diagnosed partial seizures at 105 centres, mostly in Europe and Asia.
      Randomisation to treatment groups (1:1 ratio) was by a computer-generated
      pseudorandom code (random permuted blocks), with patients sequentially assigned
      numbers by telephone. Investigators, site staff, and patients were masked to the
      assigned treatment. After randomisation, patients were titrated to either 75 mg
      oral pregabalin or 50 mg oral lamotrigine twice daily during a 4-week dose
      escalation phase, followed by a 52-week efficacy assessment phase during which
      the daily dose could be increased as needed to a maximum of 600 mg and 500 mg,
      respectively. The primary efficacy endpoint was the proportion of patients who
      remained seizure-free for 6 or more continuous months during the efficacy
      assessment phase; analysis included all patients who were randomly assigned to
      treatment groups and received at least one dose of study treatment. This study is
      registered with ClinicalTrials.gov, number NCT00280059. FINDINGS: 660 patients
      were randomly assigned to treatment groups (330 pregabalin, 330 lamotrigine), of
      whom 622 entered the efficacy assessment phase (314 pregabalin, 308 lamotrigine).
      Fewer patients in the pregabalin group than in the lamotrigine group became
      seizure-free for 6 or more continuous months (162 [52%] vs 209 [68%]; difference
      in proportion, -0.16, 95% CI -0.24 to -0.09). The overall incidence of adverse
      events was similar between the groups and consistent with that in previous
      studies; dizziness (55 [17%] vs 45 [14%] patients), somnolence (29 [9%] vs 14
      [4%]), fatigue (27 [8%] vs 19 [6%]), and weight increase (21 [6%] vs 7 [2%]) were
      numerically more common in the pregabalin group than in the lamotrigine group.
      INTERPRETATION: Pregabalin has similar tolerability but seems to have inferior
      efficacy to lamotrigine for the treatment of newly diagnosed partial seizures in
      adults. Inferior efficacy of pregabalin might have been attributable to
      limitations in the study design, as treatment doses might have not been optimised
      adequately or early enough. FUNDING: Pfizer Inc.

PMID- 21889412
TI  - Cell-mediated immune responses to inactivated trivalent influenza-vaccination are
      decreased in patients with common variable immunodeficiency.
AB  - Influenza-specific cell-mediated immune (CMI) responses can protect from
      influenza, but may be decreased in CVID-patients since defects in CMI responses
      have been demonstrated in CVID-patients. Therefore CMI responses were evaluated
      in 15 CVID-patients and 15 matched healthy controls (HC) by determining
      frequencies of interferon (IFN)gamma-producing PBMC, and frequencies of IFNgamma
      , interleukin (IL)-2- and tumour necrosis factor (TNF)alpha-producing CD4+ and
      CD8+ T-cells before and after influenza vaccination using IFNgamma enzyme-linked
      immunospot (IFNgamma-ELISpot) and flow cytometry. Humoral responses were
      determined using haemagglutination inhibition assay. In CVID-patients the number
      of spotforming PBMC in the IFNgamma-ELISpot did not increase following influenza
      vaccination, in contrast to HC. In flow cytometry, the frequencies of IFNgamma
      producing T-cells decreased in CVID-patients after influenza vaccination, while
      in HC the frequencies of IFNgamma-production flow cytometry increased.
      Concluding, CMI responses following influenza vaccination are hampered in CVID
      patients compared to HC. Additional protective strategies against influenza other
      than vaccination are warranted.

PMID- 21889413
TI  - Results of a research study evaluating WebEase, an online epilepsy self
      management program.
AB  - WebEase (Epilepsy Awareness, Support, and Education) is an online epilepsy self
      management program to assist people with taking medication, managing stress, and
      improving sleep quality. The primary study aims were to determine if those who
      participated in WebEase demonstrated improvements in medication adherence,
      perceived stress, and sleep quality. Participants were randomized to a treatment
      (T) or waitlist control (WCL) group (n=148). At follow-up, participants in the T
      group reported higher levels of medication adherence than those in the WLC group.
      Analyses were also conducted comparing those who had completed WebEase modules
      with those who had not. Those who had completed at least some modules within the
      WebEase program reported higher levels of self-efficacy and a trend toward
      significance was observed for the group*time interactions for medication
      adherence, perceived stress, self-management, and knowledge. The results
      highlight the usefulness of online tools to support self-management among people
      with epilepsy.

PMID- 21889414
TI  - Ictal singing due to left frontal lobe epilepsy: a case report and review of the
      literature.
AB  - Ictal singing has been rarely reported and the neural networks underlying this
      specific symptom remain unknown. We report a nineteen-year-old man with medically
      refractory seizures who exhibited ictal singing and laughing. He underwent
      intracranial stereotactic EEG recording which demonstrated ictal activity in
      medial and dorsolateral regions of the left frontal lobe in the generation of
      ictal singing. Thereafter, a left frontal resection of the superior and middle
      frontal gyri made him seizure-free. Among the previously reported cases of ictal
      singing, the symptomatogenic zones included bilateral frontal and temporal lobes.
      The wide variance of ictal onset zones suggests that the mechanism of ictal
      singing is probably related to the recruitment of music-related neural networks
      in different regions of both hemispheres rather than activation of a specific
      cortical region.

PMID- 21889415
TI  - Muslim nursing homes in the United States: barriers and prospects.
AB  - Historically, many nursing homes in the United States have been established by
      religious groups. This was done to provide care for the elderly when care could
      not be furnished in other venues. Despite several attempts reported in the
      literature, there are currently no Muslim nursing homes in the United States. In
      the Arab and Muslim world, the acceptance and success of such an institution has
      been somewhat variable. As the Arab Muslim population in the United States ages
      and becomes more frail, the Muslim community will have to evaluate the need to
      establish nursing homes to provide care for elderly.

PMID- 21889416
TI  - Fall prevention and monitoring of assisted living patients: an exploratory study
      of physician perspectives.
AB  - OBJECTIVE: Explore physician perspectives on their involvement in fall prevention
      and monitoring for residential care/assisted living (RC/AL) residents. DESIGN:
      Exploratory cross-sectional study; mailed questionnaire. SETTING: Four RC/AL
      communities, North Carolina. PARTICIPANTS: Primary physicians for RC/AL
      residents. MEASUREMENTS: Past Behavior and future Intentions of physicians with
      regard to (1) fall risk assessment and (2) collaboration with RC/AL staff to
      reduce falls and fall risks among RC/AL residents were explored using Theory of
      Planned Behavior (TPB) constructs. Predictor variables examined (1) physicians'
      views on their own responsibilities (Attitude), (2) their views of expectations
      from important referent groups (Subjective Norms), and (3) perceived constraints
      on engaging in fall prevention and monitoring (Perceived Behavioral Control).
      RESULTS: Physicians reported conducting fall risk assessments of 47% of RC/AL
      patients and collaborating with RC/AL staff to reduce fall risks for 36% of RC/AL
      patients (Behavior). These proportions increased to 75% and 62%, respectively,
      for future Intentions. TPB-based models explained approximately 60% of the
      variance in self-reported Behavior and Intentions. Physician's involvement in
      fall prevention and monitoring was significantly associated (P < .05) with their
      perceptions of barriers and facilitators-ease, time, reimbursement, and
      expertise. CONCLUSION: This study provides first data on physician beliefs
      regarding their involvement in fall risk assessment of RC/AL patients and
      collaboration with RC/AL staff to reduce fall risks of individual patients.
      Challenges to physician involvement identified in our study are not unique or
      specific to the RC/AL setting, and instead relate to clinical practice and
      reimbursement constraints in general.

PMID- 21889417
TI  - Cement leakage in percutaneous vertebroplasty for osteoporotic vertebral
      compression fractures: identification of risk factors.
AB  - BACKGROUND CONTEXT: Percutaneous vertebroplasty (PVP) is a common treatment
      modality for painful osteoporotic vertebral compression fractures (OVCFs). The
      complication rate of PVP is low, but cement leakage occurs in up to 90% of the
      treated levels. Recent evidence suggests that sequelae of cement leakage may be
      more common and clinically relevant than previously thought. Preoperative
      appreciation of risk factors would therefore be helpful but has not been
      thoroughly investigated. PURPOSE: Identification of preoperative risk factors for
      the occurrence of cement leakage in PVP for painful OVCFs. STUDY DESIGN:
      Retrospective assessment of risk factors using multivariate analysis. PATIENT
      SAMPLE: Eighty-nine patients treated with PVP for 177 painful OVCFs. OUTCOME
      MEASURE: Occurrence of cement leakage. METHODS: The influence of all known risk
      factors and other parameters potentially affecting the occurrence of cement
      leakage was retrospectively assessed using multivariate analysis. Patient age,
      sex, and spinal deformity index; fracture age, level, type, and semiquantitative
      severity grade (1-4), the presence of an intravertebral cleft and/or cortical
      disruption on preoperative magnetic resonance imaging (MRI), and the viscosity of
      bone cement were included. Cement leakage was assessed on direct postoperative
      computed tomography scanning of the treated levels. In addition to cement leakage
      in general, three fundamentally different leakage types (cortical, epidural, and
      anterior venous), with different possible clinical sequelae, were discerned, and
      their respective risk factors were assessed. RESULTS: In 130 of 173 (75.1%)
      treated OVCFs, cement leakage was detected. Leakage incidence was found to
      increase approximately linear with advancing severity grade. High fracture
      semiquantitative severity grade (adjusted per grade relative risk [RR], 1.14; 95%
      confidence interval [CI], 1.05-1.24; p=.002) and low bone cement viscosity
      (medium vs. low viscosity: adjusted RR, 0.73; 95% CI, 0.61-0.87; p<.001) were
      strong risk factors for cement leakage in general. For cortical leakage (in 95%
      intradiscal leakage), the presence of cortical disruption on MRI (adjusted RR,
      1.62; 95% CI, 1.16-2.26; p=.004) and an intravertebral cleft on MRI (adjusted RR,
      1.43; 95% CI, 1.07-1.77; p=.017) were identified as additional strong risk
      factors. CONCLUSIONS: High fracture severity grade and low viscosity of
      polymethylmethacrylate bone cement are general, strong, and independent risk
      factors for cement leakage. Using MRI assessment, cortical disruption and the
      presence of an intravertrebral cleft were identified as additional strong risk
      factors regarding cortical (intradiscal) cement leakage, thereby potentiating
      anticipation.

PMID- 21889418
TI  - Ionizing radiation exposure and the development of intervertebral disc
      degeneration in humans: myth or reality.

PMID- 21889419
TI  - Current management review of thoracolumbar cord syndromes.
AB  - BACKGROUND CONTEXT: Injuries to the thoracolumbar spine may lead to a complex
      array of clinical syndromes that result from dysfunction of the anterior motor
      units, lumbosacral nerve roots, and/or spinal cord. Neurologic dysfunction may
      manifest in the lower extremities as loss of fine and gross motor function,
      touch, pain, temperature, and proprioceptive and vibratory sense deficits. Two
      clinical syndromes sometimes associated with these injuries are conus medullaris
      syndrome (CMS) and cauda equina syndrome (CES). PURPOSE: To review the current
      management of thoracolumbar spinal cord injuries. STUDY DESIGN: Literature
      review. METHODS: Index Medicus was used to search the primary literature for
      articles on thoracolumbar injuries. An emphasis was placed on the current
      management, controversies, and newer treatment options. RESULTS/CONCLUSIONS:
      After blunt trauma, these syndromes may reflect a continuum of dysfunction rather
      than a distinct clinical entity. The transitional anatomy at the thoracolumbar
      junction, where the conus medullaris is present, makes it less likely that a
      "pure" CMS or CES syndrome will occur and more likely that a "mixed" injury will.
      Surgical decompression is the mainstay of treatment for incomplete spinal cord
      injury (SCI) and incomplete CMS and CES. The value of timing of surgical
      intervention in the setting of incomplete SCI is unclear at this time. This
      review summarizes the recent information on epidemiology, pathophysiology,
      diagnosis, and controversies in the management of thoracolumbar neurologic injury
      syndromes.

PMID- 21889420
TI  - Vertebral body fractures after transpsoas interbody fusion procedures.
AB  - BACKGROUND CONTEXT: Although the frequency of transpsoas lumbar interbody fusion
      procedures has increased in recent years, complication reports remain scarce in
      the literature. PURPOSE: To present four cases of vertebral body fracture after
      transpsoas interbody fusion procedures in nonosteoporotic patients without
      significant trauma and discuss relevant biomechanical factors. STUDY DESIGN: Case
      series and literature review. PATIENT SAMPLE: Patients 1 and 2 were obese men who
      underwent one- and two-level transpsoas interbody fusion procedures and
      subsequently experienced coronal plane fracture. Patients 3 and 4 were elderly
      women who underwent multilevel transpsoas interbody fusion procedures and
      experienced L5 compression fracture. RESULTS: Patients 2 and 3 were treated
      nonsurgically after fracture. The fractures healed uneventfully; however, Patient
      3 developed a flat back syndrome. Patient 1 underwent posterior instrumented
      fusion and had solid bridging bone above and below the fracture. Patient 4 was
      treated with vertebroplasty. Factors potentially contributing to these fractures
      were discussed. CONCLUSIONS: Fracture can occur after transpsoas lumbar interbody
      fusion, even in nonosteoporotic patients. Factors, such as intraoperative end
      plate breach, subsidence, compression by lateral screws, and cage rolling, could
      contribute to the development of fractures after transpsoas interbody fusion.

PMID- 21889422
TI  - Immersing the foot in painfully-cold water evokes ipsilateral extracranial
      vasodilatation.
AB  - Temporal pulse amplitude was recorded bilaterally in 56 participants before,
      during and after three ice-water immersions of the foot. Half of the participants
      were told that prolonged exposure to freezing temperatures could cause frostbite.
      Increases in pulse amplitude were greater in the ipsilateral than contralateral
      temple during and after the three foot-immersions. Although pulse amplitude
      decreased after threatening instructions and repeated immersion of the foot, the
      vasodilator response persisted during all three immersions. These findings
      suggest that nociceptive stimulation of the foot evokes an ipsilateral supra
      spinal extracranial vasodilator response, possibly as part of a broader defense
      response.

PMID- 21889421
TI  - Transcriptional activation of lysosomal exocytosis promotes cellular clearance.
AB  - Lysosomes are cellular organelles primarily involved in degradation and recycling
      processes. During lysosomal exocytosis, a Ca2+-regulated process, lysosomes are
      docked to the cell surface and fuse with the plasma membrane (PM), emptying their
      content outside the cell. This process has an important role in secretion and PM
      repair. Here we show that the transcription factor EB (TFEB) regulates lysosomal
      exocytosis. TFEB increases the pool of lysosomes in the proximity of the PM and
      promotes their fusion with PM by raising intracellular Ca2+ levels through the
      activation of the lysosomal Ca2+ channel MCOLN1. Induction of lysosomal
      exocytosis by TFEB overexpression rescued pathologic storage and restored normal
      cellular morphology both in vitro and in vivo in lysosomal storage diseases
      (LSDs). Our data indicate that lysosomal exocytosis may directly modulate
      cellular clearance and suggest an alternative therapeutic strategy for disorders
      associated with intracellular storage.

PMID- 21889423
TI  - Electrochemical determination of hydrogen peroxide with cytochrome c peroxidase
      and horse heart cytochrome c entrapped in a gelatin hydrogel.
AB  - A novel and versatile method, based on a membrane-free enzyme electrode in which
      both the enzyme and a mediator protein are entrapped in a gelatine hydrogel was
      developed for the fabrication of biosensors. As a proof of principle, we prepared
      a hydrogen peroxide biosensor by successfully entrapping both horse heart
      cytochrome c (HHC) and Saccharomyces cerevisae cytochrome c peroxidase (CCP) in a
      gelatin matrix which is immobilized on a gold electrode. This electrode was first
      pretreated with 6-mercaptohexanol. The biosensor displayed a rapid response and
      an expanded linear response range from 0 to 0.3 mM (R = 0.987) with a detection
      limit of 1 * 10(-5)M in a HEPES buffer solution (pH 7.0). This method of
      encapsulation is now further investigated for industrial biosensor applications.

PMID- 21889424
TI  - Some amino acids of the Pseudomonas aeruginosa MutL D(Q/M)HA(X)(2)E(X)(4)E
      conserved motif are essential for the in vivo function of the protein but not for
      the in vitro endonuclease activity.
AB  - Human and Saccharomyces cerevisiae MutLalpha, and some bacterial MutL proteins,
      possess a metal ion-dependent endonuclease activity which is important for the in
      vivo function of these proteins. Conserved amino acids of the C-terminal region
      of human PMS2, S. cerevisiae PMS1 and of some bacterial MutL proteins have been
      implicated in the metal-binding/endonuclease activity. However, the contribution
      of individual amino acids to these activities has not yet been fully elucidated.
      In this work we show that Pseudomonas aeruginosa MutL protein possess an in vitro
      metal ion-dependent endonuclease activity. In agreement with previous published
      results, we observed that mutation of the aspartic acid, the first histidine or
      the first glutamic acid of the conserved C-terminal DMHAAHERITYE region results
      in nonfunctional in vivo proteins. We also determined that the arginine residue
      is essential for the in vivo function of this protein. However, we unexpectedly
      observed that although the first glutamic acid mutant derivative is not
      functional in vivo, its in vitro endonuclease activity is even higher than that
      of the wild-type protein.

PMID- 21889425
TI  - Breadth by depth: expanding our understanding of the repair of transposon-induced
      DNA double strand breaks via deep-sequencing.
AB  - The transposases of DNA transposable elements catalyze the excision of the
      element from the host genome, but are not involved in the repair of the resulting
      double-strand break. To elucidate the role of various host DNA repair and damage
      response proteins in the repair of the hairpin-ended double strand breaks (DSBs)
      generated during excision of the maize Ac element in Arabidopsis thaliana, we
      deep-sequenced hundreds of thousands of somatic excision products from a variety
      of repair- or response-defective mutants. We find that each of these
      repair/response defects negatively affects the preservation of the ends,
      resulting in an enhanced frequency of deletions, insertions, and inversions at
      the excision site. The spectra of the resulting repair products demonstrate, not
      unexpectedly, that the canonical nonhomologous end joining (NHEJ) proteins DNA
      ligase IV and KU70 play an important role in the repair of the lesion generated
      by Ac excision. Our data also indicate that auxiliary NHEJ repair proteins such
      as DNA ligase VI and DNA polymerase lambda are routinely involved in the repair
      of these lesions. Roles for the damage response kinases ATM and ATR in the repair
      of transposition-induced DSBs are also discussed.

PMID- 21889426
TI  - Delayed publication of clinical trials in cystic fibrosis.
AB  - BACKGROUND: When the publication of important trial data is delayed, or data are
      never published, this will prevent the proper practice of evidence based medicine
      through robust systematic reviews. Clinical trial registries allow researchers to
      interrogate the trial protocol and afford the opportunity to identify studies
      that have been completed and so determine the time lag between completion and
      publication. METHODS: We searched ClinicalTrials.gov with the keywords 'cystic
      fibrosis'. Intervention trials which had completed 1st Jan 1998-31st Dec 2010
      were selected. Time to publication in a peer-reviewed journal was calculated.
      Survival analyses using the log rank test were undertaken. RESULTS: We identified
      142 records. Of these, 62 had full paper publications. The median time to
      publication was 3.25 years. Phase of study (phase one studies more delayed,
      p=0.024) but not source of funding (p=0.34) was associated with time to
      publication. CONCLUSIONS: Clinical trials in cystic fibrosis take a considerable
      amount of time to report their findings. More importantly, a large number of
      trials fail to report at all.

PMID- 21889427
TI  - Quantitative analysis of PD 0332991 in mouse plasma using automated micro-sample
      processing and microbore liquid chromatography coupled with tandem mass
      spectrometry.
AB  - In the oncology therapeutic area, the mouse is the primary animal model used for
      efficacy studies. Often with mouse pharmacokinetic (PK) and
      pharmacokinetic/pharmacodynamic (PK/PD) studies, less than 20 MUL of total plasma
      sample volume is available for bioanalysis due to the small size of the animal
      and the need to split samples for other measurements such as biomarker analyses.
      The need to conduct automated "small volume" sample processing for quantitative
      bioanalysis has therefore increased. An automated fit for purpose protein
      precipitation (PPT) method using a Hamilton MicroLab Star (Reno, NV, USA) to
      support mouse PK and PK/PD studies for an oncology drug candidate PD 0332991, (a
      specific inhibitor of cyclin-dependent kinase 4 (CDK-4) currently in development)
      for processing "small volumes" was developed. The automated PPT method was
      achieved by extracting and processing 10 MUL out of a minimum sample volume of 15
      MUL plasma utilizing the Hamilton MicroLab Star. A 96-conical shallow well plate
      by Agilent Technologies, Inc (Wilmington, DE, USA) was the labware of choice used
      in the automated Hamilton "small volume" method platform. Analyses of a 10 MUL
      plasma aliquot from 15 MUL of plasma study samples were conducted by both
      automated and manual PPT method. All plasma samples were quantitated using a
      Sciex API 4000 triple quadrupole mass spectrometer coupled with an Eksigent
      Express HT Ultra HPLC system. The chromatography was achieved using an Agilent
      microbore C(18) Extend, 1.0 * 50 mm, 3.5 MUm column at a flow rate of 0.150
      mL/min with a total run time of 1.8 min. Accuracy and precision of standard and
      QC concentration levels were within 90-107% and <14%, respectively. Calibration
      curves were linear over the dynamic range of 1.0-1000 ng/mL. PK studies for PD
      0332991 were conducted in female C3H mice following intravenous administration at
      1mg/kg and oral administration at 2mg/kg. PK values such as area under curve
      (AUC), volume of distribution (Vd), clearance (Cl), half life (T(1/2)) and
      bioavailability (F%) demonstrated less than 11% difference between the automated
      Hamilton and manual PPT methods. The results demonstrate that the automated
      Hamilton PPT method can accurately and precisely aliquot 10 MUL of plasma from 15
      MUL or larger volume plasma samples. The fit for purpose Hamilton PPT method is
      suitable for routine analyses of plasma samples from micro-sampling PK and PK/PD
      samples to support discovery studies.

PMID- 21889428
TI  - Socioeconomic disparities and the familial coexistence of child stunting and
      maternal overweight in Guatemala.
AB  - The double burden of malnutrition, defined here as households with a stunted
      child and an overweight mother (SCOM), is a growing problem in Guatemala. We
      explored the magnitude of SCOM and the identification of socio-economic factors
      associated with this malnutrition duality. From the 2000 Living Standards
      Measurement Study from Guatemala, we obtained a sample of 2492 households with
      pairs of children 6-60 months and their mothers (18-49 years) and estimated the
      prevalence of SCOM. Economic characteristics of this sample were assessed with
      the Concentration Index (CI). Results revealed higher prevalence of child
      stunting, but a lower prevalence of maternal overweight among the poor compared
      to the rich households. Economic inequality in child stunting was greater than
      economic inequality in maternal overweight (CI=-0.22 vs. +0.14). SCOM pairs were
      more prevalent among the poor and middle SES groups as compared to the rich
      households. A multivariate logistic regression model showed that SCOM was more
      likely to occur in households from the middle consumption quintile than in those
      from the first quintile (odds ratio=1.7). The findings reported here add new
      insights into the complex phenomenon observed in households with both extremes of
      the malnutrition continuum, and support the need for the identification of
      economic, social and biological interventions aimed at, on the one hand, the
      prevention of this duality of the malnutrition in those households where it is
      still non-existent, and on the other hand, to deter or correct the economic,
      social and biological environments where those mother-child dyads are already
      affected by such phenomena.

PMID- 21889429
TI  - Internalization of the thin and muscular body ideal and disordered eating in
      adolescence: the mediation effects of body esteem.
AB  - This study investigates body esteem factors (weight-esteem and appearance-esteem)
      as mediators of the relationship between 'internalization of the ideal body
      figure' and disordered eating behaviors (restrained, emotional and external
      eating) in a community sample of adolescent males (n=810) and females (n=1137)
      from the Ontario Research on Eating and Adolescent Lifestyles (REAL) study.
      Mediation models were examined using a bootstrapping approach to test indirect
      effects and indirect contrasts. In males, weight-esteem partially mediated the
      relationship between muscular ideal and restrained eating; appearance-esteem
      partially mediated effects in the emotional and external eating regressions. In
      females, both weight-esteem and appearance-esteem partially mediated the
      relationship between thin ideal and all three forms of disordered eating; weight
      esteem was a stronger mediator for restrained eating, and appearance-esteem a
      stronger mediator for emotional and external eating. Body esteem is important to
      consider for prevention and treatment of disordered eating in both genders.

PMID- 21889430
TI  - Thrombotic and bleeding disorders in perinatal medicine.

PMID- 21889431
TI  - Factors that may influence midwives work-related stress and burnout.
AB  - RESEARCH QUESTION: To determine the incidence and level of work-related stress
      and burnout in midwives and contributing and protective demographic factors that
      may influence those levels. PARTICIPANTS AND METHOD: All registered midwives
      (152) working in two public hospital maternity units within the same health
      service district in NSW completed the Maslach Burnout Inventory Human Services
      Survey and a demographic survey including care model, shift work, lifestyle data
      and exercise level. FINDINGS: There was a response rate of 36.8% with 56 (56/152)
      midwives completing the surveys. Almost two thirds (60.7%) of midwives in this
      sample experienced moderate to high levels of emotional exhaustion, a third
      (30.3%) scoring low personal accomplishment and a third (30.3%) experiencing
      depersonalization related to burnout. Significant differences were found among
      groups of midwives according to years in the profession, shifts worked, how many
      women with multiple psychosocial issues were included in the midwife's workload
      and the midwife's uptake of physical exercise. Those midwives who had spent
      longer in the profession and exercised scored low burnout levels. CONCLUSION: The
      impact of years in the profession, shifts worked, how many women with multiple
      psychosocial issues were included in their workload and the midwife's level of
      exercise significantly affected how these midwives dealt with burnout and
      provided care for women. As the response rate was low, and the study cannot be
      generalised to the entire midwifery workforce but provides important insights for
      further research. Understanding factors related to burnout can benefit health
      care institutions financially and in terms of human costs, especially in view of
      consistent international shortages of midwives.

PMID- 21889432
TI  - Submental sensitive transcutaneous electrical stimulation (SSTES) at home in
      neurogenic oropharyngeal dysphagia: a pilot study.
AB  - OBJECTIVE: Oropharyngeal dysphagia is frequent in chronic neurological disorders
      and increases mortality, mainly due to pulmonary complications. Our aim was to
      show that submental sensitive transcutaneous electrical stimulation (SSTES)
      applied during swallowing at home can improve swallowing function in patients
      with chronic neurological disorders. METHODS: Thirteen patients were recruited
      for the study (4 f, 68 +/- 12 years). They all suffered from neurogenic
      oropharyngeal dysphagia. We first compared the swallowing of paste and liquid
      with and without SSTES. Thereafter, the patients were asked to perform SSTES at
      home with each meal. Swallowing was evaluated before and after six weeks of SSTES
      using the SWAL-QoL questionnaire. RESULTS: With the stimulator switch turned on,
      swallowing coordination improved, with a decrease in swallow reaction time for
      the liquid (P<0.05) and paste boluses (P<0.01). Aspiration scores also decreased
      significantly with the electrical stimulations (P<0.05), with no change in
      stasis. At-home compliance was excellent and most patients tolerated the
      electrical stimulations with no discomfort. A comparison of the SWAL-QoL
      questionnaires after 6 weeks revealed an improvement in the burden (P=0.001),
      fatigue (P<0.05), and pharyngeal symptom (P<0.001) scales. CONCLUSION: The
      present study demonstrated that SSTES is easy to use at home and improves
      oropharyngeal dysphagia quality of life.

PMID- 21889433
TI  - Racial differences in the presentation and outcomes of chronic lymphocytic
      leukemia and variants in the United States.
AB  - BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common form of adult
      leukemia in the United States, and prolymphocytic leukemia (PLL) is a related,
      rare chronic lymphoproliferative disorder. METHODS: Using the United States
      Surveillance, Epidemiology and End Results (SEER) data from 13 registries, we
      examined differences in incidence and survival for CLL, small lymphocytic
      lymphoma (SLL) and PLL by race. International Classification of Diseases for
      Oncology 3(rd) edition histology codes 9670, 9823, and 9632-34 were used to
      identify cases. RESULTS: From 1992 to 2007, 30,622 cases of CLL/SLL and 268 cases
      of PLL were recorded. Males had higher incidence than females (male-to-female
      incidence rate ratio CLL/SLL 1.89, 95% confidence interval (CI) 1.85-1.94 and PLL
      2.47, 95%CI 1.90-3.20). Black patients were diagnosed at younger age compared to
      white patients (mean age at diagnosis for white versus black patients for
      CLL/SLL, 70 versus 67 years, P < .001; for PLL, 71 versus 61 years, P < .001).
      Greater proportion of black patients with SLL presented with B symptoms,
      extranodal primary site, and advanced disease compared to white patients (P =
      .003, P = .012, and P = .009 respectively). White patients with CLL/SLL had
      better survival rates than black patients (5-year relative survival rate 77.1%
      versus 63.9%, P < .01). In univariate Cox regression models, black race, male
      gender, age at diagnosis > 65 years, advanced stage, and B-symptoms were
      predictors of worse survival (P < .01) among CLL/SLL patients. CONCLUSIONS: Black
      patients with CLL/SLL and PLL present at younger age and black patients with
      CLL/SLL have worse survival than white patients. Epidemiological studies
      examining the biological variants of these diseases in concert with race are
      needed to elucidate the etiology of these disparities.

PMID- 21889434
TI  - EBV-positive diffuse large b-cell lymphoma in young immunocompetent individuals.

PMID- 21889435
TI  - Ribosomal protein metallopanstimulin-1 impairs multiple myeloma CAG cells growth
      and inhibits fibroblast growth factor receptor 3.
AB  - INTRODUCTION: It was demonstrated that metallopanstimulin-1 (MPS-1, RPS27)
      inhibited the growth of tumors formed by head and neck squamous cell carcinoma
      cells and reduced paxillin gene expression. METHODS: The present study examined
      whether and how MPS-1 affects another type of cancer, multiple myeloma (CAG).
      Enhanced expression of MPS-1 dramatically inhibited CAG in vitro and in vivo.
      RESULTS: Overexpression of MPS-1 resulted in decreased fibroblast growth factor
      (FGF2) receptor 3 and impaired endogenous MAPK/ErK signaling. MAPK/ErK signaling
      was not stimulated by adding recombinant FGF2 to myeloma cells overexpressing MPS
      1. CONCLUSIONS: These data suggest that MPS-1 suppresses CAG growth and that
      weakened FGF2 signaling may contribute to this effect.

PMID- 21889436
TI  - Genetic and environmental influences on impulsivity: a meta-analysis of twin,
      family and adoption studies.
AB  - A meta-analysis of twin, family and adoption studies was conducted to estimate
      the magnitude of genetic and environmental influences on impulsivity. The best
      fitting model for 41 key studies (58 independent samples from 14 month old
      infants to adults; N=27,147) included equal proportions of variance due to
      genetic (0.50) and non-shared environmental (0.50) influences, with genetic
      effects being both additive (0.38) and non-additive (0.12). Shared environmental
      effects were unimportant in explaining individual differences in impulsivity.
      Age, sex, and study design (twin vs. adoption) were all significant moderators of
      the magnitude of genetic and environmental influences on impulsivity. The
      relative contribution of genetic effects (broad sense heritability) and unique
      environmental effects were also found to be important throughout development from
      childhood to adulthood. Total genetic effects were found to be important for all
      ages, but appeared to be strongest in children. Analyses also demonstrated that
      genetic effects appeared to be stronger in males than in females. Method of
      assessment (laboratory tasks vs. questionnaires), however, was not a significant
      moderator of the genetic and environmental influences on impulsivity. These
      results provide a structured synthesis of existing behavior genetic studies on
      impulsivity by providing a clearer understanding of the relative genetic and
      environmental contributions in impulsive traits through various stages of
      development.

PMID- 21889437
TI  - Collective motion of surfactant-producing bacteria imparts superdiffusivity to
      their upper surface.
AB  - Swarming bacteria move on agar surfaces in groups, using flagella as motive
      organelles. Motility depends critically on surface wetness, which is enabled by
      osmotic agents and surfactants secreted by the bacteria. In a recent study, the
      upper surface of an Escherichia coli swarm was found to be stationary, as
      determined from the motion of MgO particles deposited on the swarm. This led to
      the remarkable conclusion that the bacteria move between two stationary surfaces
      the agar gel below and the liquid/air interface above. That study suggested that
      secreted surfactants may contribute to immobilizing the upper surface of a swarm.
      Here, we test this proposition using two robust surfactant-producing bacteria. We
      find antithetically that the upper surfaces of both these swarms are mobile,
      showing a superdiffusive behavior in swarms with stronger surfactant activity.
      Superdiffusive behavior was not observed on the surface of a drop of bacterial
      culture, on bacteria-free culture supernatant, or on nonswarming surfactant
      producer colonies, which suggests that superdiffusion is an emergent property
      resulting from the interaction of the collective motion of the bacteria within
      the swarm with the surfactant layer above. Swarming not only allows bacteria to
      forage for food, but also confers protective advantages against antimicrobial
      agents. Our results are therefore relevant to superdiffusive strategies in
      biological foraging and survival.

PMID- 21889438
TI  - Rapid, massively parallel single-cell drug response measurements via live cell
      interferometry.
AB  - A central question in cancer therapy is how individual cells within a population
      of tumor cells respond to drugs designed to arrest their growth. However, the
      absolute growth of cells, their change in physical mass, whether cancerous or
      physiologic, is difficult to measure directly with traditional techniques. Here,
      we develop live cell interferometry for rapid, real-time quantification of cell
      mass in cells exposed to a changing environment. We used tunicamycin induction of
      the unfolded protein stress response in multiple myeloma cells to generate a mass
      response that was temporally profiled for hundreds of cells simultaneously.
      Within 2 h, the treated cells were growth suppressed compared to controls, with a
      few cells in both populations showing a robust increase (+15%) or little change
      (<5%) in mass accumulation. Overall, live cell interferometry provides a
      conceptual advance for assessing cell populations to identify, monitor, and
      measure single cell responses, such as to therapeutic drugs.

PMID- 21889440
TI  - Spontaneous contractility-mediated cortical flow generates cell migration in
      three-dimensional environments.
AB  - We present a model of cell motility generated by actomyosin contraction of the
      cell cortex. We identify, analytically, dynamical instabilities of the cortex and
      show that they yield steady-state cortical flows, which, in turn, can induce cell
      migration in three-dimensional environments. This mechanism relies on the
      regulation of contractility by myosin, whose transport is explicitly taken into
      account in the model. Theoretical predictions are compared to experimental data
      of tumor cells migrating in three-dimensional matrigel and suggest that this
      mechanism could be a general mode of cell migration in three-dimensional
      environments.

PMID- 21889439
TI  - Bistability of cell adhesion in shear flow.
AB  - Cell adhesion plays a central role in multicellular organisms helping to maintain
      their integrity and homeostasis. This complex process involves many different
      types of adhesion proteins, and synergetic behavior of these proteins during cell
      adhesion is frequently observed in experiments. A well-known example is the
      cooperation of rolling and stationary adhesion proteins during the leukocytes
      extravasation. Despite the fact that such cooperation is vital for proper
      functioning of the immune system, its origin is not fully understood. In this
      study we constructed a simple analytic model of the interaction between a
      leukocyte and the blood vessel wall in shear flow. The model predicts existence
      of cell adhesion bistability, which results from a tug-of-war between two kinetic
      processes taking place in the cell-wall contact area-bond formation and rupture.
      Based on the model results, we suggest an interpretation of several cytoadhesion
      experiments and propose a simple explanation of the existing synergy between
      rolling and stationary adhesion proteins, which is vital for effective cell
      adherence to the blood vessel walls in living organisms.

PMID- 21889441
TI  - Similar endothelial glycocalyx structures in microvessels from a range of
      mammalian tissues: evidence for a common filtering mechanism?
AB  - The glycocalyx or endocapillary layer on the luminal surface of microvessels has
      a major role in the exclusion of macromolecules from the underlying endothelial
      cells. Current structural evidence in the capillaries of frog mesentery indicates
      a regularity in the structure of the glycocalyx, with a center-to-center fiber
      spacing of 20 nm and a fiber width of 12 nm, which might explain the observed
      macromolecular filtering properties. In this study, we used electron micrographs
      of tissues prepared using perfusion fixation and tannic acid treatment. The
      digitized images were analyzed using autocorrelation to find common spacings and
      to establish whether similar structures, hence mechanisms, are present in the
      microvessel glycocalyces of a variety of mammalian tissues. Continuous glycocalyx
      layers in mammalian microvessels of choroid, renal tubules, glomerulus, and psoas
      muscle all showed similar lateral spacings at ~19.5 nm (possibly in a
      quasitetragonal lattice) and longer spacings above 100 nm. Individual glycocalyx
      tufts above fenestrations in the first three of these tissues and also in stomach
      fundus and jejunum showed evidence for similar short-range structural regularity,
      but with more disorder. The fiber diameter was estimated as 18.8 (+/- 0.2) nm,
      but we believe this is an overestimate because of the staining method used. The
      implications of these findings are discussed.

PMID- 21889442
TI  - Rectification of the channelrhodopsin early conductance.
AB  - We analyzed the nonlinear current-voltage relationships of the early conducting
      state of channelrhodopsin-2 expressed in Xenopus oocytes and human embryonic
      kidney cells with respect to changes of the electrochemical gradients of H(+),
      Na(+)/K(+), and Ca(2+)/Mg(2+). Several models were tested for wild-type ChR2 and
      mutations at positions E90, E123, H134, and T159. Voltage-gating was excluded as
      cause for the nonlinearity. However, a general enzyme kinetic model with one
      predominant binding site yielded good fits throughout. The empty site with an
      apparent charge number of about -0.3 and strong external cation binding causes
      some inward rectification of the uniport function. Additional inward
      rectification is due to asymmetric competition from outside between the
      transported ion species. Significant improvement of the fits was achieved by
      introducing an elastic voltage-divider formed by the voltage-sensitive barriers.

PMID- 21889443
TI  - The LIM domain of zyxin is sufficient for force-induced accumulation of zyxin
      during cell migration.
AB  - Cellular responses to mechanical perturbation are vital to cell physiology. In
      particular, migrating cells have been shown to sense substrate stiffness and
      alter cell morphology and speed. Zyxin is a focal adhesion protein that responds
      to external mechanical forces; however, the mechanisms of zyxin recruitment at
      force-bearing sites are unknown. Using force-sensing microfabricated substrates,
      we simultaneously measured traction force and zyxin recruitment at force-bearing
      sites. GFP-tagged zyxin accumulates at force-bearing sites at the leading edge,
      but not at the trailing edge, of migrating epithelial cells. Zyxin recruitment at
      force-bearing sites depends on Rho-kinase and myosin II activation, suggesting
      that zyxin responds not only to the externally applied force, as previously
      shown, but also to the internally generated actin-myosin force. Zyxin in turn
      recruits vasodilator-stimulated phosphoprotein, a regulator of actin assembly, to
      force-bearing sites. To dissect the domains of zyxin that are essential for this
      unique force-dependent accumulation, we generated two zyxin truncation mutants:
      one lacking the LIM domain (DeltaLIM) and one containing only the LIM domain with
      all three LIM motifs (LIM). GFP-tagged DeltaLIM does not localize to the force
      bearing sites, but GFP-tagged zyxin LIM-domain is sufficient for the recruitment
      to and dynamics at force-bearing focal adhesions. Furthermore, one or two LIM
      motifs are not sufficient for force-dependent accumulation, suggesting that all
      three LIM motifs are required. Therefore, the LIM domain of zyxin recruits zyxin
      to force-bearing sites at the leading edge of migrating cells.

PMID- 21889444
TI  - Biomimetic N-terminal alkylation of peptoid analogues of surfactant protein C.
AB  - Surfactant protein C (SP-C) is a hydrophobic lipopeptide that is critical for
      lung function, in part because it physically catalyzes the formation of surface
      associated surfactant reservoirs. Many of SP-C's key biophysical properties
      derive from its highly stable and hydrophobic alpha-helix. However, SP-C's
      posttranslational modification with N-terminal palmitoyl chains also seems to be
      quite important. We created a new (to our knowledge) class of variants of a
      synthetic, biomimetic family of peptide mimics (peptoids) that allow us to study
      the functional effects of biomimetic N-terminal alkylation in vitro. Mimics were
      designed to emulate the amphipathic patterning, helicity, and hydrophobicity of
      SP-C, and to include no, one, or two vicinal amide-linked, N-terminal octadecyl
      chains (providing a reach equivalent to that of natural palmitoyl chains).
      Pulsating bubble surfactometry and Langmuir-Wilhelmy surface balance studies
      showed that alkylation improved biomimetic surface activities, yielding lower
      film compressibility and lower maximum dynamic surface tensions. Atomic force
      microscopy studies indicated that alkyl chains bind to and retain segregated
      interfacial surfactant phases at low surface tensions by inducing 3D structural
      transitions in the monolayer's fluid-like phase, forming surfactant-associated
      reservoirs. Peptoid-based SP-C mimics are easily produced and purified, and offer
      much higher chemical and secondary structure stability than polypeptide-based
      mimics. In surfactant replacements intended for medical use, synthetic SP mimics
      reduce the odds of pathogen contamination, which may facilitate the wider use of
      surfactant treatment of respiratory disorders and diseases.

PMID- 21889445
TI  - Amphipathic antimicrobial piscidin in magnetically aligned lipid bilayers.
AB  - The amphipathic antimicrobial peptide piscidin 1 was studied in magnetically
      aligned phospholipid bilayers by oriented-sample solid-state NMR spectroscopy.
      (31)P NMR and double-resonance (1)H/(15)N NMR experiments performed between 25 
      degrees C and 61  degrees C enabled the lipid headgroups as well as the peptide
      amide sites to be monitored over a range of temperatures. The alpha-helical
      peptide dramatically affects the phase behavior and structure of anionic bilayers
      but not those of zwitterionic bilayers. Piscidin 1 stabilizes anionic bilayers,
      which remain well aligned up to 61  degrees C when piscidin 1 is on the membrane
      surface. Two-dimensional separated-local-field experiments show that the tilt
      angle of the peptide is 80 +/- 5 degrees , in agreement with previous results on
      mechanically aligned bilayers. The peptide undergoes fast rotational diffusion
      about the bilayer normal under these conditions, and these studies demonstrate
      that magnetically aligned bilayers are well suited for structural studies of
      amphipathic peptides.

PMID- 21889446
TI  - Hemagglutinin fusion peptide mutants in model membranes: structural properties,
      membrane physical properties, and PEG-mediated fusion.
AB  - While the importance of viral fusion peptides (e.g., hemagglutinin (HA) and gp41)
      in virus-cell membrane fusion is established, it is unclear how these peptides
      enhance membrane fusion, especially at low peptide/lipid ratios for which the
      peptides are not lytic. We assayed wild-type HA fusion peptide and two mutants,
      G1E and G13L, for their effects on the bilayer structure of 1,2-dioleoyl-3-sn
      phosphatidylcholine/1,2-dioleoyl-3-sn
      phosphatidylethanolamine/Sphingomyelin/Cholesterol (35:30:15:20) membranes, their
      structures in the lipid bilayer, and their effects on membrane fusion. All
      peptides bound to highly curved vesicles, but fusion was triggered only in the
      presence of poly(ethylene glycol). At low (1:200) peptide/lipid ratios, wild-type
      peptide enhanced remarkably the extent of content mixing and leakage along with
      the rate constants for these processes, and significantly enhanced the bilayer
      interior packing and filled the membrane free volume. The mutants caused no
      change in contents mixing or interior packing. Circular dichroism, polarized
      attenuated total-internal-reflection Fourier-transform infrared spectroscopy
      measurements, and membrane perturbation measurements all conform to the inverted
      V model for the structure of wild-type HA peptide. Similar measurements suggest
      that the G13L mutant adopts a less helical conformation in which the N-terminus
      moves closer to the bilayer interface, thus disrupting the V-structure. The G1E
      peptide barely perturbs the bilayer and may locate slightly above the interface.
      Fusion measurements suggest that the wild-type peptide promotes conversion of the
      stalk to an expanded trans-membrane contact intermediate through its ability to
      occupy hydrophobic space in a trans-membrane contact structure. While wild-type
      peptide increases the rate of initial intermediate and final pore formation, our
      results do not speak to the mechanisms for these effects, but they do leave open
      the possibility that it stabilizes the transition states for these events.

PMID- 21889447
TI  - Hysteresis-based mechanism for the directed motility of the Ncd motor.
AB  - Ncd is a Kinesin-14 family protein that walks to the microtubule's minus end.
      Although available structures show its alpha-helical neck in either pre- or post
      stroke orientations, little is known about the transition between these two
      states. Using a combination of molecular dynamics simulations and structural
      analyses, we find that the neck sequentially makes intermediate contacts with the
      motor head along its mostly longitudinal path, and it develops a 24 degrees 
      twist in the post-stroke orientation. The forward (pre-stroke to post-stroke)
      motion has an ~4.5 k(B)T (where k(B) is the Boltzmann constant, and T=300 K) free
      energy barrier and is a diffusion guided by the intermediate contacts. The post
      stroke free-energy minimum is higher and is formed ~10 degrees  before reaching
      the orientation in the post-stroke crystal structure, consistent with previous
      structural data. The importance of intermediate contacts correlates with the
      existing motility data, including those for mutant Ncds. Unlike the forward
      motion, the recovery stroke goes nearly downhill in free energy, powered in part
      by torsional relaxation of the neck. The hysteresis in the energetics of the neck
      motion arises from the mechanical compliance of the protein, and together with
      guided diffusion, it may be key to the directed motility of Ncd.

PMID- 21889448
TI  - Disrupting the myosin converter-relay interface impairs Drosophila indirect
      flight muscle performance.
AB  - Structural interactions between the myosin converter and relay domains have been
      proposed to be critical for the myosin power stroke and muscle power generation.
      We tested this hypothesis by mutating converter residue 759, which interacts with
      relay residues I508, N509, and D511, to glutamate (R759E) and determined the
      effect on Drosophila indirect flight muscle mechanical performance. Work loop
      analysis of mutant R759E indirect flight muscle fibers revealed a 58% and 31%
      reduction in maximum power generation (P(WL)) and the frequency at which maximum
      power (f(WL)) is generated, respectively, compared to control fibers at 15 
      degrees C. Small amplitude sinusoidal analysis revealed a 30%, 36%, and 32%
      reduction in mutant elastic modulus, viscous modulus, and mechanical rate
      constant 2pib, respectively. From these results, we infer that the mutation
      reduces rates of transitions through work-producing cross-bridge states and/or
      force generation during strongly bound states. The reductions in muscle power
      output, stiffness, and kinetics were physiologically relevant, as mutant wing
      beat frequency and flight index decreased about 10% and 45% compared to control
      flies at both 15  degrees C and 25  degrees C. Thus, interactions between the
      relay loop and converter domain are critical for lever-arm and catalytic domain
      coordination, high muscle power generation, and optimal Drosophila flight
      performance.

PMID- 21889449
TI  - High-affinity quasi-specific sites in the genome: how the DNA-binding proteins
      cope with them.
AB  - Many prokaryotic transcription factors home in on one or a few target sites in
      the presence of a huge number of nonspecific sites. Our analysis of lambda
      repressor in the Escherichia coli genome based on single basepair substitution
      experiments shows the presence of hundreds of sites having binding energy within
      3 Kcal/mole of the O(R)1 binding energy, and thousands of sites with binding
      energy above the nonspecific binding energy. The effect of such sites on DNA
      based processes has not been fully explored. The presence of such sites
      dramatically lowers the occupation probability of the specific site far more than
      if the genome were composed of nonspecific sites only. Our Brownian dynamics
      studies show that the presence of quasi-specific sites results in very
      significant kinetic effects as well. In contrast to lambda-repressor, the E. coli
      genome has orders of magnitude lower quasi-specific sites for GalR, an integral
      transcription factor, thus causing little competition for the specific site. We
      propose that GalR and perhaps repressors of the same family have evolved binding
      modes that lead to much smaller numbers of quasi-specific sites to remove the
      untoward effects of genomic DNA.

PMID- 21889450
TI  - Predicting the effects of basepair mutations in DNA-protein complexes by
      thermodynamic integration.
AB  - Thermodynamically rigorous free energy methods in principle allow the exact
      computation of binding free energies in biological systems. Here, we use
      thermodynamic integration together with molecular dynamics simulations of a DNA
      protein complex to compute relative binding free energies of a series of mutants
      of a protein-binding DNA operator sequence. A guanine-cytosine basepair that
      interacts strongly with the DNA-binding protein is mutated into adenine-thymine,
      cytosine-guanine, and thymine-adenine. It is shown that basepair mutations can be
      performed using a conservative protocol that gives error estimates of ~10% of the
      change in free energy of binding. Despite the high CPU-time requirements, this
      work opens the exciting opportunity of being able to perform basepair scans to
      investigate protein-DNA binding specificity in great detail computationally.

PMID- 21889451
TI  - The binding process of a nonspecific enzyme with DNA.
AB  - Protein-DNA recognition of a nonspecific complex is modeled to understand the
      nature of the transient encounter states. We consider the structural and
      energetic features and the role of water in the DNA grooves in the process of
      protein-DNA recognition. Here we have used the nuclease domain of colicin E7 (N
      ColE7) from Escherichia coli in complex with a 12-bp DNA duplex as the model
      system to consider how a protein approaches, encounters, and associates with DNA.
      Multiscale simulation studies using Brownian dynamics and molecular-dynamics
      simulations were performed to provide the binding process on multiple length- and
      timescales. We define the encounter states and identified the spatial and
      orientational aspects. For the molecular length-scales, we used molecular
      dynamics simulations. Several intermediate binding states were found, which have
      different positions and orientations of protein around DNA including major and
      minor groove orientations. The results show that the contact number and the
      hydrated interfacial area are measures that facilitate better understanding of
      sequence-independent protein-DNA binding landscapes and pathways.

PMID- 21889452
TI  - Orientation of cyanine fluorophores terminally attached to DNA via long, flexible
      tethers.
AB  - Cyanine fluorophores are commonly used in single-molecule FRET experiments with
      nucleic acids. We have previously shown that indocarbocyanine fluorophores
      attached to the 5'-termini of DNA and RNA via three-carbon atom linkers stack on
      the ends of the helix, orienting their transition moments. We now investigate the
      orientation of sulfoindocarbocyanine fluorophores tethered to the 5'-termini of
      DNA via 13-atom linkers. Fluorescence lifetime measurements of
      sulfoindocarbocyanine 3 attached to double-stranded DNA indicate that the
      fluorophore is extensively stacked onto the terminal basepair at 15  degrees C,
      with properties that depend on the terminal sequence. In single molecules of
      duplex DNA, FRET efficiency between sulfoindocarbocyanine 3 and 5 attached in
      this manner is modulated with helix length, indicative of fluorophore orientation
      and consistent with stacked fluorophores that can undergo lateral motion. We
      conclude that terminal stacking is an intrinsic property of the cyanine
      fluorophores irrespective of the length of the tether and the presence or absence
      of sulfonyl groups. However, compared to short-tether indocarbocyanine, the mean
      rotational relationship between the two fluorophores is changed by ~60 degrees 
      for the long-tether sulfoindocarbocyanine fluorophores. This is consistent with
      the transition moments becoming approximately aligned with the long axis of the
      terminal basepair for the long-linker species.

PMID- 21889453
TI  - Development of a "modular" scheme to describe the kinetics of transcript
      elongation by RNA polymerase.
AB  - Transcript elongation by RNA polymerase involves the sequential appearance of
      several alternative and off-pathway states of the transcript elongation complex
      (TEC), and this complicates modeling of the kinetics of the transcription
      elongation process. Based on solutions of the chemical master equation for such
      transcription systems as a function of time, we here develop a modular scheme for
      simulating such kinetic transcription data. This scheme deals explicitly with the
      problem of TEC desynchronization as transcript synthesis proceeds, and develops
      kinetic modules to permit the various alternative states of the TECs (paused
      states, backtracked states, arrested states, and terminated states) to be
      introduced one-by-one as needed. In this way, we can set up a comprehensive
      kinetic model of appropriate complexity to fit the known transcriptional
      properties of any given DNA template and set of experimental conditions,
      including regulatory cofactors. In the companion article, this modular scheme is
      successfully used to model kinetic transcription elongation data obtained by bulk
      gel electrophoresis quenching procedures and real-time surface plasmon resonance
      methods from a template of known sequence that contains defined pause, stall, and
      termination sites.

PMID- 21889454
TI  - Fitting experimental transcription data with a comprehensive template-dependent
      modular kinetic model.
AB  - In the companion article, we developed a modular scheme for representing the
      kinetics of transcription elongation by RNA polymerase. As an example of how to
      use these approaches, in this article we use a comprehensive modular model of
      this sort to fit experimental transcript elongation results obtained on the
      canonical tR2 template of phage lambda by means of complementary bulk gel
      electrophoresis and surface plasmon resonance assays. The gel electrophoresis
      results, obtained in experiments quenched at various times after initiation of
      transcription, provide distributions of RNA lengths as a function of time. The
      surface plasmon resonance methods were used to monitor increases and decreases in
      the total mass of transcription elongation complexes in the same experiments. The
      different measures of transcription dynamics that these methods provide allow us
      to use them in combination to obtain a set of largely robust and well-defined
      kinetic parameters. The results show that our modular approach can be used to
      develop and test predictive kinetic schemes that can be fit to real transcription
      elongation data. They also suggest that these approaches can be extended to
      simulate the kinetics of other processes that involve the processive extension or
      shortening of nucleic acid chains and related systems of sequential branching
      reaction events.

PMID- 21889455
TI  - Rationalizing 5000-fold differences in receptor-binding rate constants of four
      cytokines.
AB  - The four cytokines erythropoietin (EPO), interleukin-4 (IL4), human growth
      hormone (hGH), and prolactin (PRL) all form four-helix bundles and bind to type I
      cytokine receptors. However, their receptor-binding rate constants span a 5000
      fold range. Here, we quantitatively rationalize these vast differences in rate
      constants by our transient-complex theory for protein-protein association. In the
      transient complex, the two proteins have near-native separation and relative
      orientation, but have yet to form the short-range specific interactions of the
      native complex. The theory predicts the association rate constant as
      k(a)=k(a0)exp(-DeltaG(el)(*)/k(B)T) where k(a0) is the basal rate constant for
      reaching the transient complex by random diffusion, and the Boltzmann factor
      captures the rate enhancement due to electrostatic attraction. We found that the
      vast differences in receptor-binding rate constants of the four cytokines arise
      mostly from the differences in charge complementarity among the four cytokine
      receptor complexes. The basal rate constants (k(a0)) of EPO, IL4, hGH, and PRL
      were similar (5.2 * 10(5) M(-1)s(-1), 2.4 * 10(5) M(-1)s(-1), 1.7 * 10(5) M(-1)s(
      1), and 1.7 * 10(5) M(-1)s(-1), respectively). However, the average electrostatic
      free energies (DeltaG(e1)(*)) were very different (-4.2 kcal/mol, -2.4 kcal/mol, 
      0.1 kcal/mol, and -0.5 kcal/mol, respectively, at ionic strength=160 mM). The
      receptor-binding rate constants predicted without adjusting any parameters, 6.2 *
      10(8) M(-1)s(-1), 1.3 * 10(7) M(-1)s(-1), 2.0 * 10(5) M(-1)s(-1), and 7.6 * 10(4)
      M(-1)s(-1), respectively, for EPO, IL4, hGH, and PRL agree well with experimental
      results. We uncover that these diverse rate constants are anticorrelated with the
      circulation concentrations of the cytokines, with the resulting cytokine-receptor
      binding rates very close to the limits set by the half-lives of the receptors,
      suggesting that these binding rates are functionally relevant and perhaps
      evolutionarily tuned. Our calculations also reproduced well-observed effects of
      mutations and ionic strength on the rate constants and produced a set of
      mutations on the complex of hGH with its receptor that putatively enhances the
      rate constant by nearly 100-fold through increasing charge complementarity. To
      quantify charge complementarity, we propose a simple index based on the charge
      distribution within the binding interface, which shows good correlation with
      DeltaG(e1)(*). Together these results suggest that protein charges can be
      manipulated to tune k(a) and control biological function.

PMID- 21889456
TI  - On the involvement of single-bond rotation in the primary photochemistry of
      photoactive yellow protein.
AB  - Prior experimental observations, as well as theoretical considerations, have led
      to the proposal that C(4)-C(7) single-bond rotation may play an important role in
      the primary photochemistry of photoactive yellow protein (PYP). We therefore
      synthesized an analog of this protein's 4-hydroxy-cinnamic acid chromophore, (5
      hydroxy indan-(1E)-ylidene)acetic acid, in which rotation across the C(4)-C(7)
      single bond has been locked with an ethane bridge, and we reconstituted the apo
      form of the wild-type protein and its R52A derivative with this chromophore
      analog. In PYP reconstituted with the rotation-locked chromophore, 1), absorption
      spectra of ground and intermediate states are slightly blue-shifted; 2), the
      quantum yield of photochemistry is ~60% reduced; 3), the excited-state dynamics
      of the chromophore are accelerated; and 4), dynamics of the thermal recovery
      reaction of the protein are accelerated. A significant finding was that the yield
      of the transient ground-state intermediate in the early phase of the photocycle
      was considerably higher in the rotation-locked samples than in the corresponding
      samples reconstituted with p-coumaric acid. In contrast to theoretical
      predictions, the initial photocycle dynamics of PYP were observed to be not
      affected by the charge of the amino acid residue at position 52, which was varied
      by 1), varying the pH of the sample between 5 and 10; and 2), site-directed
      mutagenesis to construct R52A. These results imply that C(4)-C(7) single-bond
      rotation in PYP is not an alternative to C(7)=C(8) double-bond rotation, in case
      the nearby positive charge of R52 is absent, but rather facilitates, presumably
      with a compensatory movement, the physiological Z/E isomerization of the blue
      light-absorbing chromophore.

PMID- 21889457
TI  - Solution and solid-state NMR structural studies of antimicrobial peptides LPcin-I
      and LPcin-II.
AB  - Lactophoricin (LPcin-I) is an antimicrobial, amphiphatic, cationic peptide with
      23-amino acid residues isolated from bovine milk. Its analogous peptide, LPcin
      II, lacks six N-terminal amino acids compared to LPcin-I. Interestingly, LPcin-II
      does not display any antimicrobial activity, whereas LPcin-I inhibits the growth
      of both Gram-negative and Gram-positive bacteria without exhibiting any hemolytic
      activity. Uniformly (15)N-labeled LPcin peptides were prepared by the recombinant
      expression of fusion proteins in Escherichia coli, and their properties were
      characterized by electrospray ionization mass spectrometry, circular dichroism
      spectroscopy, and antimicrobial activity tests. To understand the structure
      activity relationship of these two peptides, they were studied in model membrane
      environments by a combination of solution and solid-state NMR spectroscopy. We
      determined the tertiary structure of LPcin-I and LPcin-II in the presence of
      dodecylphosphorylcholine micelles by solution NMR spectroscopy. Magnetically
      aligned unflipped bicelle samples were used to investigate the structure and
      topology of LPcin-I and LPcin-II by solid-state NMR spectroscopy.

PMID- 21889458
TI  - Effect of zinc binding on beta-amyloid structure and dynamics: implications for
      Abeta aggregation.
AB  - Assembly of beta-amyloid (Abeta) peptide into toxic oligomers is widely believed
      to initiate Alzheimer's disease pathogenesis. Under in vitro physiological
      conditions, zinc (Zn(II)) can bind to Abeta and redirect its assembly from
      amyloid fibrillar toward less toxic amorphous aggregation. Propensity of Abeta to
      go toward a specific form of aggregate state is determined by structural and
      dynamical properties of the initial monomeric as well as the aggregate state.
      Here we probe the structural and dynamical impact of binding of Zn(II) to
      monomeric Abeta40 using NMR spectroscopy. To obtain further support for the
      importance of intrinsic dynamics in the aggregation precursor, (15)N relaxation
      measurements were also performed for Abeta42, the more fibrillar aggregation
      prone variant of Abeta. The combined data suggest that, upon Zn(II)-binding to
      the N-terminus of Abeta40, a relatively rigid turnlike structure is induced at
      residues Val(24)-Lys(28) whereas the residues flanking this region become more
      mobile on the picosecond-to-nanosecond timescale. This is in contrast to the
      increased rigidity of Abeta42 at the C-terminus, and proposed to be linked to the
      higher propensity of Zn(II)-bound peptide to form amorphous aggregates with less
      entropic penalties than their fibrillar counterparts.

PMID- 21889459
TI  - Molecular dynamics simulation of Bombolitin II in the
      dipalmitoylphosphatidylcholine membrane bilayer.
AB  - The orientation behavior of Bombolitin II (BLT2) in the
      dipalmitoylphosphatidylcholine membrane bilayer was investigated by using
      molecular-dynamics simulation. During the 20-ns simulation, the BLT2 began to
      tilt and finally reached the angle of 51 degrees  from the membrane-normal. The
      structure of the peptide formed the amphipathic alpha-helical structure during
      the entire simulation time. The peptide tilts with its hydrophobic side faced to
      the hydrophobic core of the bilayer. We analyzed the mechanism of the tilting
      behavior of the peptide associated with the membrane in detail. The analysis
      showed that the hydrogen-bond interaction and the electrostatic interaction were
      found to exist between Lys(12) and a lipid molecule. These interactions are
      considered to work as an important factor in tilting the peptide to the membrane
      normal.

PMID- 21889460
TI  - Microsecond unfolding kinetics of sheep prion protein reveals an intermediate
      that correlates with susceptibility to classical scrapie.
AB  - The microsecond folding and unfolding kinetics of ovine prion proteins (ovPrP)
      were measured under various solution conditions. A fragment comprising residues
      94-233 of the full-length ovPrP was studied for four variants with differing
      susceptibilities to classical scrapie in sheep. The observed biexponential
      unfolding kinetics of ovPrP provides evidence for an intermediate species.
      However, in contrast to previous results for human PrP, there is no evidence for
      an intermediate under refolding conditions. Global analysis of the kinetic data,
      based on a sequential three-state mechanism, quantitatively accounts for all
      folding and unfolding data as a function of denaturant concentration. The
      simulations predict that an intermediate accumulates under both folding and
      unfolding conditions, but is observable only in unfolding experiments because the
      intermediate is optically indistinguishable from the native state. The relative
      population of intermediates in two ovPrP variants, both transiently and under
      destabilizing equilibrium conditions, correlates with their propensities for
      classical scrapie. The variant susceptible to classical scrapie has a larger
      population of the intermediate state than the resistant variant. Thus, the
      susceptible variant should be favored to undergo the PrP(C) to PrP(Sc) conversion
      and oligomerization.

PMID- 21889461
TI  - Differential mechanical stability of filamin A rod segments.
AB  - Prompted by recent reports suggesting that interaction of filamin A (FLNa) with
      its binding partners is regulated by mechanical force, we examined mechanical
      properties of FLNa domains using magnetic tweezers. FLNa, an actin cross-linking
      protein, consists of two subunits that dimerize through a C-terminal self
      association domain. Each subunit contains an N-terminal spectrin-related actin
      binding domain followed by 24 immunoglobulinlike (Ig) repeats. The Ig repeats in
      the rod 1 segment (repeats 1-15) are arranged as a linear array, whereas rod 2
      (repeats 16-23) is more compact due to interdomain interactions. In the rod 1
      segment, repeats 9-15 augment F-actin binding to a much greater extent than do
      repeats 1-8. Here, we report that the three segments are unfolded at different
      forces under the same loading rate. Remarkably, we found that repeats 16-23 are
      susceptible to forces of ~10 pN or even less, whereas the repeats in the rod 1
      segment can withstand significantly higher forces. The differential force
      response of FLNa Ig domains has broad implications, since these domains not only
      support the tension of actin network but also interact with many transmembrane
      and signaling proteins, mostly in the rod 2 segment. In particular, our finding
      of unfolding of repeats 16-23 at ~10 pN or less is consistent with the
      hypothesized force-sensing function of the rod 2 segment in FLNa.

PMID- 21889462
TI  - Structure and dynamics of oligomeric intermediates in beta2-microglobulin self
      assembly.
AB  - beta(2)-Microglobulin is a 99-residue protein with a propensity to form amyloid
      like fibrils in vitro which exhibit distinct morphologies dependent on the
      solution conditions employed. Here we have used ion mobility spectrometry-mass
      spectrometry to characterize the oligomeric species detected during the formation
      of worm-like fibrils of beta(2)-microglobulin at pH 3.6. Immediately upon sample
      dissolution, beta(2)-microglobulin monomer and oligomers-the latter ranging in
      size from dimer to hexamer-are present as a pool of rapidly interconverting
      species. Increasing the ionic strength of the solution initiates fibril formation
      without a lag-phase whereupon these oligomers become more stable and higher-order
      species (7-mer to >14-mer) are observed. The oligomers detected have collision
      cross-sectional areas consistent with a linearly stacked assembly comprising
      subunits of native-like volume. The results provide insights into the identity
      and properties of the transient, oligomeric intermediates formed during assembly
      of worm-like fibrils and identify species that differ significantly from the
      oligomers previously characterized during the nucleated assembly of long,
      straight fibrils. The data presented demonstrate the interrelationship between
      different fibril-forming pathways and identify their points of divergence.

PMID- 21889463
TI  - Structured functional domains of myelin basic protein: cross talk between actin
      polymerization and Ca(2+)-dependent calmodulin interaction.
AB  - The 18.5-kDa myelin basic protein (MBP), the most abundant isoform in human adult
      myelin, is a multifunctional, intrinsically disordered protein that maintains
      compact assembly of the sheath. Solution NMR spectroscopy and a hydrophobic
      moment analysis of MBP's amino-acid sequence have previously revealed three
      regions with high propensity to form strongly amphipathic alpha-helices. These
      regions, located in the central, N- and C-terminal parts of the protein, have
      been shown to play a role in the interactions of MBP with cytoskeletal proteins,
      Src homology 3-domain-containing proteins, Ca(2+)-activated calmodulin (Ca(2+)
      CaM), and myelin-mimetic membrane bilayers. Here, we have further characterized
      the structure-function relationship of these three domains. We constructed three
      recombinant peptides derived from the 18.5-kDa murine MBP: (A22-K56), (S72-S107),
      and (S133-S159) (which are denoted alpha1, alpha2, and alpha3, respectively). We
      used a variety of biophysical methods (circular dichroism spectroscopy,
      isothermal titration calorimetry, transmission electron microscopy, fluorimetry,
      and solution NMR spectroscopy and chemical shift index analysis) to characterize
      the interactions of these peptides with actin and Ca(2+)-CaM. Our results show
      that all three peptides can adopt alpha-helical structure inherently even in
      aqueous solution. Both alpha1- and alpha3-peptides showed strong binding with
      Ca(2+)-CaM, and both adopted an alpha-helical conformation upon interaction, but
      the binding of the alpha3-peptide appeared to be more dynamic. Only the alpha1
      peptide exhibited actin polymerization and bundling activity, and the addition of
      Ca(2+)-CaM resulted in depolymerization of actin that had been polymerized by
      alpha1. The results of this study proved that there is an N-terminal binding
      domain in MBP for Ca(2+)-CaM (in addition to the primary site located in the C
      terminus), and that it is sufficient for CaM-induced actin depolymerization.
      These three domains of MBP represent molecular recognition fragments with
      multiple roles in both membrane- and protein-association.

PMID- 21889464
TI  - A modified FCCS procedure applied to Ly49A-MHC class I cis-interaction studies in
      cell membranes.
AB  - The activity of natural killer (NK) cells is regulated by a fine-tuned balance
      between activating and inhibitory receptors. Dual-color fluorescence cross
      correlation spectroscopy (FCCS) was used to directly demonstrate a so-called cis
      interaction between a member of the inhibitory NK cell receptor family Ly49
      (Ly49A), and its ligand, the major histocompatibility complex (MHC) class I,
      within the plasma membrane of the same cell. By a refined FCCS model, calibrated
      by positive and negative control experiments on cells from the same lymphoid cell
      line, concentrations and diffusion coefficients of free and interacting proteins
      could be determined on a collection of cells. Using the intrinsic intercellular
      variation of their expression levels for titration, it was found that the
      fraction of Ly49A receptors bound in cis increase with increasing amounts of MHC
      class I ligand. This increase shows a tendency to be more abrupt than for a
      diffusion limited - three dimensional bimolecular reaction, which most likely
      reflects the two-dimensional confinement of the reaction. For the Ly49A- MHC
      class I interaction it indicates that within a critical concentration range the
      local concentration level of MHC class I can provide a distinct regulation
      mechanism of the NK cell activity.

PMID- 21889465
TI  - Submolecular-scale imaging of alpha-helices and C-terminal domains of tubulins by
      frequency modulation atomic force microscopy in liquid.
AB  - In this study, we directly imaged subnanometer-scale structures of tubulins by
      performing frequency modulation atomic force microscopy (FM-AFM) in liquid.
      Individual alpha-helices at the surface of a tubulin protofilament were imaged as
      periodic corrugations with a spacing of 0.53 nm, which corresponds to the common
      pitch of an alpha-helix backbone (0.54 nm). The identification of individual
      alpha-helices allowed us to determine the orientation of the deposited tubulin
      protofilament. As a result, C-terminal domains of tubulins were identified as
      protrusions with a height of 0.4 nm from the surface of the tubulin. The imaging
      mechanism for the observed subnanometer-scale contrasts is discussed in relation
      to the possible structures of the C-terminal domains. Because the C-terminal
      domains are chemically modified to regulate the interactions between tubulins and
      other biomolecules (e.g., motor proteins and microtubule-associated proteins),
      detailed structural information on individual C-terminal domains is valuable for
      understanding such regulation mechanisms. The results obtained in this study
      demonstrate that FM-AFM is capable of visualizing the structural variation of
      tubulins with subnanometer resolution. This is an important first step toward
      using FM-AFM to analyze the functions of tubulins.

PMID- 21889466
TI  - STED nanoscopy of actin dynamics in synapses deep inside living brain slices.
AB  - It is difficult to investigate the mechanisms that mediate long-term changes in
      synapse function because synapses are small and deeply embedded inside brain
      tissue. Although recent fluorescence nanoscopy techniques afford improved
      resolution, they have so far been restricted to dissociated cells or tissue
      surfaces. However, to study synapses under realistic conditions, one must image
      several cell layers deep inside more-intact, three-dimensional preparations that
      exhibit strong light scattering, such as brain slices or brains in vivo. Using
      aberration-reducing optics, we demonstrate that it is possible to achieve
      stimulated emission depletion superresolution imaging deep inside scattering
      biological tissue. To illustrate the power of this novel (to our knowledge)
      approach, we resolved distinct distributions of actin inside dendrites and spines
      with a resolution of 60-80 nm in living organotypic brain slices at depths up to
      120 MUm. In addition, time-lapse stimulated emission depletion imaging revealed
      changes in actin-based structures inside spines and spine necks, and showed that
      these dynamics can be modulated by neuronal activity. Our approach greatly
      facilitates investigations of actin dynamics at the nanoscale within functionally
      intact brain tissue.

PMID- 21889467
TI  - Determination of IL28B polymorphisms in liver biopsies obtained after liver
      transplantation.
AB  - BACKGROUND & AIMS: Recipient and donor IL28B polymorphisms seem to play an
      important role in the response to hepatitis C treatment after liver
      transplantation (LT). Since donor peripheral blood mononuclear cells (PBMC) are
      not always available, the aim of our study was to assess whether follow-up
      biopsies obtained after LT could be used to determine donor IL28B genotype.
      METHODS: Genotyping of IL28B rs12979860 was performed by TaqMan real-time PCR and
      direct sequencing in 56 HCV-infected LT recipients and their donors. Liver
      biopsies were obtained at the moment of LT (reperfusion) and at any time when
      clinically indicated (follow-up). Direct sequencing always confirmed the real
      time PCR results. RESULTS: Genotyping of donor IL28B rs12979860 polymorphisms
      showed a 100% match both in PBMC and reperfusion biopsies. The frequency of IL28B
      rs12979860 polymorphisms differed significantly between donors and follow-up
      biopsies (p=0.024). We found an enrichment of the IL28B rs12979860 CT genotype
      (72%) in follow-up biopsies compared to donor samples (46%). Recipient alleles
      were clearly detected in 14 heterozygous follow-up samples: 10 CT/CC, 1 CT/TT,
      and 3 TT/CC (recipient/donor), thus reflecting a mixture of both donor and
      recipient genotypes. CONCLUSIONS: Our results support that follow-up liver
      biopsies from LT recipients are not suitable for determining donor IL28B
      rs12979860 genotype by TaqMan real-time PCR or direct sequencing and that PBMC or
      reperfusion biopsies should be used instead. Thus, it is very important to obtain
      adequate samples in order to accurately determine the relative contributions of
      both donor and recipient.

PMID- 21889468
TI  - Relative performances of FibroTest, Fibroscan, and biopsy for the assessment of
      the stage of liver fibrosis in patients with chronic hepatitis C: a step toward
      the truth in the absence of a gold standard.
AB  - BACKGROUND & AIMS: Liver fibrosis stage is traditionally assessed with biopsy, an
      imperfect gold standard. Two widely used techniques, FibroTest(r), and liver
      stiffness measurement (LSM) using Fibroscan(r) have been validated using biopsy,
      and therefore the true performances of these estimates are still unknown in the
      absence of a perfect reference. The aim was to assess the relative accuracy of
      FibroTest, LSM, and biopsy using methods without gold standard in patients with
      chronic hepatitis C (CHC) and controls. METHODS: A total of 1289 patients with
      CHC and 604 healthy volunteers, with assessment of fibrosis stage by the three
      techniques, and alanine aminotransferase (ALT) taken as a control test, were
      analyzed by latent class method with random effects. In the volunteers, the false
      positive risk of biopsy was obtained from a large surgical sample of four normal
      livers. RESULTS: The latent class model with random effects permitted to
      conciliate the observed data and estimates of test performances. For advanced
      fibrosis, the specificity/sensitivity was for FibroTest 0.93/0.70, LSM 0.96/0.45,
      ALT 0.79/0.78 and biopsy 0.67/0.63, and for cirrhosis FibroTest 0.87/0.41, LSM
      0.93/0.39, ALT 0.78/0.08 and biopsy 0.95/0.51. The analysis of the discordances
      between pairs suggested that the variability of the model was mainly related to
      the discordances between biopsy and LSM (residuals>10; p<0.0001). CONCLUSIONS: A
      method without the use of a gold standard confirmed the accuracy of FibroTest and
      Fibroscan for the diagnosis of advanced fibrosis and cirrhosis in patients with
      chronic hepatitis C. The variability of the model was mostly due to the
      discordances between Fibroscan and biopsy.

PMID- 21889469
TI  - Hepatotoxicity associated with statins: reports of idiosyncratic liver injury
      post-marketing.
AB  - BACKGROUND & AIMS: Limited data exist on drug-induced liver injury (DILI)
      associated with statins. METHODS: Reports on adverse reactions suspected to be
      due to statins received by the Swedish Adverse Drug Reactions Advisory Committe
      1988-2010 were analyzed. Only cases with >5*upper limit of normal (ULN) in
      aminotransferases and/or alkaline phosphatase >2*ULN were included. RESULTS: The
      most common types of ADRs suspected were DILI in 124/217 (57%) cases. A total of
      73/124 (59%) cases had at least possible relationship, median age 64 years (57
      73), 55% males, whereas 25/124 cases (20%) were excluded due to mild elevations
      of liver tests and 26 due to unlikely relationship and/or lack of data. A statin
      related DILI episode was reported in 1.2/100,000 users. Atorvastatin was
      implicated in 30/73 (41%) cases, simvastatin in 28 (38%), fluvastatin (15%), and
      others. Two patients died of acute liver failure, one underwent liver
      transplantation and 25 (34%) had jaundice. Three patients were rechallenged with
      the same statin producing similar patterns of liver injury. The median duration
      of therapy was 90 days (30-120), 120 (39-248) for atorvastatin, and 75 (30-150)
      for simvastatin (NS). Cholestatic/mixed injury was more common with atorvastatin,
      17/30 (56%) than with simvastatin, 7/28 (24%) (p=0.018). CONCLUSIONS:
      Idiosyncratic liver injury associated with statins is rare but can be severe.
      After recovery, a similar pattern of liver injury can be reproduced on re
      exposure. Most patients experience liver injury 3-4 months after start of
      therapy. Atorvastatin is mostly associated with cholestatic liver injury whereas
      hepatocellular injury is more common with simvastatin.

PMID- 21889470
TI  - Motion detection technology as a tool for cardiopulmonary resuscitation (CPR)
      quality improvement.

PMID- 21889471
TI  - Pauses during CPR--are breaks hindering our efforts?

PMID- 21889472
TI  - Continuous capnography and ultrasound-based airway management.

PMID- 21889473
TI  - Resolving the M-cell debate: mechanics matters.

PMID- 21889475
TI  - Imaging of size-dependent uptake and identification of novel pathways in mouse
      Peyer's patches using fluorescent organosilica particles.
AB  - We investigated size-dependent uptake of fluorescent thiol-organosilica particles
      by Peyer's patches (PPs). We performed an oral single-particle administration
      (95, 130, 200, 340, 695 and 1050 nm) and a simultaneous dual-particle
      administration using 2 kinds of particles. Histological imaging and quantitative
      analysis revealed that particles taken up by the PP subepithelial dome were size
      dependent, and there was an optimal size range for higher uptake. Quantitative
      analysis of simultaneous dual-particle administration revealed that the
      percentage of fluorescence areas for 95, 130, 200, 340, 695 and 1050 nm with
      respect to 110 nm area was 124.0, 89.1, 73.8, 20.2, 9.2 and 0.5%, respectively.
      Additionally, imaging using fluorescent thiol-organosilica particles could detect
      2 novel pathways through mouse PP epithelium: the transcellular pathway and the
      paracellular pathway. The uptake of nanoparticles based on an optimal size range
      and 2 novel pathways could indicate a new approach for vaccine delivery and
      nanomedicine development. FROM THE CLINICAL EDITOR: Studying various sizes of
      fluorescent organosilica particles and their uptake in Peyer's patches, this team
      of authors determined the optimal size range of administration. Two novel
      pathways through mouse Peyer's patch epithelium were detected, i.e., the
      transcellular pathway and the paracellular pathway. This observation may have
      important applications in future vaccine delivery and nano-drug delivery.

PMID- 21889474
TI  - Accessing the genomic effects of naked nanoceria in murine neuronal cells.
AB  - Cerium oxide nanoparticles (nanoceria) are engineered nanoparticles whose
      versatility is due to their unique redox properties. We and others have
      demonstrated that naked nanoceria can act as antioxidants to protect cells
      against oxidative damage. Although the redox properties may be beneficial, the
      genome-wide effects of nanoceria on gene transcription and associated biological
      processes remain elusive. Here we applied a functional genomic approach to
      examine the genome-wide effects of nanoceria on global gene transcription and
      cellular functions in mouse neuronal cells. Importantly, we demonstrated that
      nanoceria induced chemical- and size-specific changes in the murine neuronal cell
      transcriptome. The nanoceria contributed more than 83% of the population of
      uniquely altered genes and were associated with a unique spectrum of genes
      related to neurological disease, cell cycle control, and growth. These
      observations suggest that an in-depth assessment of potential health effects of
      naked nanoceria and other naked nanoparticles is both necessary and imminent.
      FROM THE CLINICAL EDITOR: Cerium oxide nanoparticles are important antioxidants,
      with potential applications in neurodegenerative conditions. This team of
      investigators demonstrated the genomic effects of nanoceria, showing that it
      induced chemical- and size-specific changes in the murine neuronal cell
      transcriptome.

PMID- 21889476
TI  - Increased anticoagulant activity of thrombin-binding DNA aptamers by nanoscale
      organization on DNA nanostructures.
AB  - Control over thrombin activity is much desired to regulate blood clotting in
      surgical and therapeutic situations. Thrombin-binding RNA and DNA aptamers have
      been used to inhibit thrombin activity and thus the coagulation cascade. Soluble
      DNA aptamers, as well as two different aptamers tethered by a flexible single
      strand linker, have been shown to possess anticoagulant activity. Here, we link
      multiple aptamers at programmed positions on DNA nanostructures to optimize
      spacing and orientation of the aptamers and thereby to maximize anticoagulant
      activity in functional assays. By judicious engineering of the DNA
      nanostructures, we have created a novel, functional DNA nanostructure, which is a
      multi-aptamer inhibitor with activity eightfold higher than free aptamer.
      Reversal of the thrombin inhibition was also achieved by the use of single
      stranded DNA antidotes, thus enabling significant control over blood coagulation.
      FROM THE CLINICAL EDITOR: Thrombin inhibition via DNA aptamers has recently
      become a possibility. In this study, thrombin-binding DNA aptamers were further
      optimized by nanoscale organization on DNA nanostructures. The authors have
      created a novel, functional DNA nanostructure, which is a multi-aptamer inhibitor
      with activity eightfold higher than that of free aptamer. Reversal of thrombin
      inhibition was also achieved by single-stranded DNA antidotes, enabling
      significant control over the coagulation pathway.

PMID- 21889477
TI  - Physiological validation of cell health upon probing with carbon nanotube
      endoscope and its benefit for single-cell interrogation.
AB  - New-generation nanoscale devices for single-cell study are intensively being
      developed. As has been shown, nanodevices are minimally invasive because of their
      order-of-magnitude smaller size in comparison to conventional glass pipettes.
      However, in most studies the evaluation of the nanodevice impact on cell health
      has not extended to their effects on cell metabolic integrity. In this work we
      evaluated the degree to which the insertion of a carbon-based nanotube endoscope
      into a cell induces mechanical and biochemical stress, and affects cellular key
      metabolic systems. The effects of insertion of the nanotube endoscope on cell
      morphological and physiological modulations were monitored and compared to those
      of glass micropipettes. We report that nanotube endoscope insertion does not
      significantly modulate the plasma membrane and actin network. The cell metabolic
      mechanisms such as energy production and inositol 1,4,5-trisphosphate-dependent
      calcium signaling remain preserved for prolonged endoscope presence within a
      cell. FROM THE CLINICAL EDITOR: In this basic science study, the effects of
      insertion of carbon nanotube endoscope on cell morphological and physiological
      modulations were monitored and compared to those of glass micropipettes. Nanotube
      endoscope insertion is truly minimally invasive: it does not significantly
      modulate the plasma membrane and actin network; the energy production and
      inositol 1,4,5-trisphosphate-dependent calcium signaling also remain preserved
      during prolonged endoscope presence within a cell.

PMID- 21889478
TI  - Self-assembling peptide-based nanoparticles enhance cellular delivery of the
      hydrophobic anticancer drug ellipticine through caveolae-dependent endocytosis.
AB  - A special class of self-assembling peptide (EAK16-II) has been found to stabilize
      the hydrophobic anticancer agent ellipticine (EPT) in aqueous solution. In this
      study, the mechanism of such peptide-EPT complexes to enhance cellular delivery
      and anticancer activity was evaluated. Results revealed that EAK16-II can form
      nanoparticles with EPT, having an average size of ~100 nm. This nanoformulation
      had cytotoxicity to human lung carcinoma A549 cells that was comparable to EPT
      dissolved in dimethyl sulfoxide. It enhanced EPT uptake drastically when compared
      to the microformulation. Such enhanced uptake was significantly reduced by
      inhibitors specifically for the caveolae-dependent pathway. We also found both
      protonated and neutral forms of EPT present in the cells. Interestingly, both
      were found in the cytoplasm, co-localized with LysoTracker, whereas only
      protonated EPT was seen in the nucleus. The promising therapeutic efficacy,
      specific delivery pathway, and intracellular distribution pattern discovered in
      this work may help further develop EPT as a nanoformulation for clinical
      applications. FROM THE CLINICAL EDITOR: A special class of self-assembling
      peptide (EAK16-II) has been found to stabilize ellipticine in aqueous solution.
      The authors demonstrate therapeutic efficacy, describe specific delivery
      pathways, and effective intracellular distribution pattern, which will aid the
      development of this technology for future clinical applications.

PMID- 21889479
TI  - Nanoparticles in the treatment and diagnosis of neurological disorders: untamed
      dragon with fire power to heal.
AB  - The incidence of neurological diseases of unknown etiology is increasing,
      including well-studied diseases such as Alzhiemer's, Parkinson's, and multiple
      sclerosis. The blood-brain barrier provides protection for the brain but also
      hinders the treatment and diagnosis of these neurological diseases, because the
      drugs must cross the blood-brain barrier to reach the lesions. Thus, attention
      has turned to developing novel and effective delivery systems that are capable of
      carrying drug and that provide good bioavailability in the brain.
      Nanoneurotechnology, particularly application of nanoparticles in drug delivery,
      has provided promising answers to some of these issues in recent years. Here we
      review the recent advances in the understanding of several common forms of
      neurological diseases and particularly the applications of nanoparticles to treat
      and diagnose them. In addition, we discuss the integration of bioinformatics and
      modern genomic approaches in the development of nanoparticles. FROM THE CLINICAL
      EDITOR: In this review paper, applications of nanotechnology-based diagnostic
      methods and therapeutic modalities are discussed addressing a variety of
      neurological disorders, with special attention to blood-brain barrier delivery
      methods. These novel nanomedicine approaches are expected to revolutionize
      several aspects of clinical neurology.

PMID- 21889480
TI  - Nanovesicle aerosols as surfactant therapy in lung injury.
AB  - Acute lung injury causes inactivation of pulmonary surfactant due to leakage of
      albumin and other markers. Current surfactants are ineffective in this condition
      and are instilled intratracheally. Nanovesicles of 300 +/- 50 nm composed of
      nonlamellar phospholipids were developed as pulmonary surfactant aerosols for
      therapy in acid-induced lung injury. A combination of dipalmitoyl
      phosphatidylcholine and dioleoyl phosphatidylethanolamine was used. The size and
      composition of the nanovesicles were optimized for an improved airway patency in
      the presence of albumin and serum. In an acid-induced lung injury model in mice,
      on treatment with nanovesicle aerosols at a dose of 200 mg/kg, the alveolar
      protein leakage decreased from 8.62 +/- 0.97 MUg/mL to 1.94 +/- 0.74 MUg/mL,
      whereas the airway patency of the bronchoalveolar lavage fluid increased from 0.6
      +/- 0.0% to 91.7 +/- 1.05%. Nanovesicle aerosols of nonlamellar lipids improved
      the resistance of pulmonary surfactants to inhibition and were promising as a
      noninvasive aerosol therapy in acute lung injury. FROM THE CLINICAL EDITOR: In
      acute lung injury, intrinsic surfactants are inactivated via albumin leakage and
      other mechanisms. Currently existing intratracheal surfactants are ineffective in
      this condition. The authors demonstrate that novel nanovesicle aerosols of
      nonlamellar lipids improved the resistance of pulmonary surfactants to inhibition
      and are promising as a noninvasive aerosol therapy in acute lung injury.

PMID- 21889482
TI  - DNA melting analysis: application of the "open tube" format for detection of
      mutant KRAS.
AB  - High-resolution melting (HRM) analysis is a very effective method for genotyping
      and mutation scanning that is usually performed just after PCR amplification (the
      "closed tube" format). Though simple and convenient, the closed tube format makes
      the HRM dependent on the PCR mix, not generally optimal for DNA melting analysis.
      Here, the "open tube" format, namely the post-PCR optimization procedure
      (amplicon shortening and solution chemistry modification), is proposed. As a
      result, mutation scanning of short amplicons becomes feasible on a standard real
      time PCR instrument (not primarily designed for HRM) using SYBR Green I. This
      approach has allowed us to considerably enhance the sensitivity of detecting
      mutant KRAS using both low- and high-resolution systems (the Bio-Rad iQ5-SYBR
      Green I and Bio-Rad CFX96-EvaGreen, respectively). The open tube format, though
      more laborious than the closed tube one, can be used in situations when maximal
      sensitivity of the method is needed. It also permits standardization of DNA
      melting experiments and the introduction of instruments of a "lower level" into
      the range of those suitable for mutation scanning.

PMID- 21889481
TI  - RNA Foci, CUGBP1, and ZNF9 are the primary targets of the mutant CUG and CCUG
      repeats expanded in myotonic dystrophies type 1 and type 2.
AB  - Expansions of noncoding CUG and CCUG repeats in myotonic dystrophies type 1 (DM1)
      and DM2 cause complex molecular pathology, the features of which include
      accumulation of RNA aggregates and misregulation of the RNA-binding proteins
      muscleblind-like 1 (MBNL1) and CUG-binding protein 1 (CUGBP1). CCUG repeats also
      decrease amounts of the nucleic acid binding protein ZNF9. Using tetracycline
      (Tet)-regulated monoclonal cell models that express CUG and CCUG repeats, we
      found that low levels of long CUG and CCUG repeats result in nuclear and
      cytoplasmic RNA aggregation with a simultaneous increase of CUGBP1 and a
      reduction of ZNF9. Elevation of CUGBP1 and reduction of ZNF9 were also observed
      before strong aggregation of the mutant CUG/CCUG repeats. Degradation of CUG and
      CCUG repeats normalizes ZNF9 and CUGBP1 levels. Comparison of short and long CUG
      and CCUG RNAs showed that great expression of short repeats form foci and alter
      CUGBP1 and ZNF9; however, long CUG/CCUG repeats misregulate CUGBP1 and ZNF9 much
      faster than high levels of the short repeats. These data suggest that correction
      of DM1 and DM2 might be achieved by complete and efficient degradation of CUG and
      CCUG repeats or by a simultaneous disruption of CUG/CCUG foci and correction of
      CUGBP1 and ZNF9.

PMID- 21889483
TI  - Local and global factors affecting RNA sequencing analysis.
AB  - High-throughput RNA sequencing (RNA-seq) continues to provide unparalleled
      insight into transcriptome complexity. Now the "gold standard" for assessing
      global transcript levels, RNA-seq is poised to revolutionize our understanding of
      transcription and posttranscriptional regulation of RNA. Despite significant
      advantages over prior experimental strategies, RNA-seq is not without pitfalls.
      We have identified a number of confounding factors that significantly affect
      sequencing coverage. These include regional GC content, preferential sites of
      fragmentation, and read "pile-up" due to primer affinity and transcript end
      effects. Independent of cell type and laboratory, when ignored, these factors can
      bias analyses. Understanding the underlying principles responsible for producing
      these artifacts is key to recognizing both their presence and how their effects
      may be controlled. Here we outline the causes of and strategies to avoid several
      previously unreported complicating factors common to RNA-seq experiments.

PMID- 21889484
TI  - Characterization of the 3':5' ratio for reliable determination of RNA quality.
AB  - Determination of RNA quality is a critical first step in obtaining meaningful
      gene expression data. The PCR-based 3':5' assay is an RNA quality assessment
      tool. This assay is a simple, fast, and low-cost method of selecting samples for
      further analysis. However, its practical applications are unexploited primarily
      because of the absence of an experimental threshold. We show that, by anchoring
      the 5' assay a specific distance from the 3' end of the sequence and by spacing
      the 3' at a distance of a number of nucleotides, a cutoff determines whether a
      sample is suitable for downstream quantification studies.

PMID- 21889485
TI  - Foam fractionation of protein: correlation of protein adsorption onto bubbles
      with a pH-induced conformational transition.
AB  - A foam fractionation apparatus was prepared to aid protein separation at the gas
      liquid interface. Using lysozyme as a model protein, we investigated the
      alteration of enzymatic and optical activities through foaming. The lysozyme
      transferred to the gaseous nitrogen phase after 5 min of bubbling with no
      exogenous detergent. The bacteriolytic and optical activities of lysozyme from
      the foamate were nearly equivalent to those of the original lysozyme. This result
      indicated that lysozyme did not irreversibly denature during foam fractionation.
      We then performed protein separation using binary mixtures of lysozyme and alpha
      amylase. When the two proteins were dissolved in bulk solution of pH 10.5, which
      is close to the isoelectric point (pI) of lysozyme (10.7), selective
      fractionation of lysozyme from the foam was observed. Indeed, this fractionation
      was identical to that from a single component solution of lysozyme. Similarly,
      selective fractionation of alpha-amylase was achieved in pH 3.0 buffer.
      Furthermore, circular dichroism (CD) and subsequent model fitting revealed that
      the protein had a reduced or nearly complete absence of alpha-helical content,
      whereas the amount of beta-sheet structure and random coil was elevated in the
      buffer conditions that promoted protein adsorption. These results indicate that a
      pH-induced conformational transition might correlate with protein foaming.

PMID- 21889486
TI  - Development of a high-throughput method for the determination of pharmacological
      levels of plasma D-serine.
AB  - D-Serine administration has been shown to be effective for the treatment of
      schizophrenia symptoms. However, D-Serine must be administered at high doses to
      observe clinical effects. This is due in large part to D-Serine undergoing
      oxidation by D-Serine acid oxidase (DAAO) before it reaches the brain.
      Consequently, coadministration of D-Serine with a DAAO inhibitor has been
      suggested as a way to lower the dose of D-serine required to treat schizophrenia.
      During the characterization of DAAO inhibitors as potential drugs, inhibitors are
      evaluated in rodents for their ability to increase plasma D-Serine levels after
      oral coadministration. Current high-performance liquid chromatography (HPLC)
      based methodologies to measure D-Serine in plasma are time-consuming and are not
      amenable to concomitant analysis of multiple samples. We report the
      characterization of a 96-well format assay to monitor D-Serine in plasma that
      greatly expedites analysis time. The assay involves the use of strong cation
      exchange solid phase extraction (SPE) to isolate D-Serine from plasma followed by
      quantitation of D-Serine using the DAAO-catalyzed reaction. Plasma D-Serine
      determination using this assay could also be used as pharmacodynamic marker and
      as biomarker.

PMID- 21889487
TI  - Tanshinone II-A attenuates and stabilizes atherosclerotic plaques in
      apolipoprotein-E knockout mice fed a high cholesterol diet.
AB  - Tanshinone II-A (Tan), a bioactive diterpene isolated from Salvia miltiorrhiza
      Bunge (Danshen), possesses anti-oxidant and anti-inflammatory activities. The
      present study investigated whether Tan can decrease and stabilize atherosclerotic
      plaques in Apolipoprotein-E knockout (ApoE(-/-)) mice maintained on a high
      cholesterol diet (HCD). Six week-old mice challenged with a HCD were randomly
      assigned to 4 groups: (a) C57BL/6J; (b) ApoE(-/-); (c) ApoE(-/-)+Tan-30 (30
      mg/kg/d); (d) ApoE(-/-)+Tan-10 (10mg/kg/d). After 16 weeks of intervention, Tan
      treated mice showed decreased atherosclerotic lesion size in the aortic sinus and
      en face aorta. Furthermore, immunohistochemical analysis revealed that Tan
      rendered the lesion composition a more stable phenotype as evidenced by reduced
      necrotic cores, decreased macrophage infiltration, and increased smooth muscle
      cell and collagen contents. Tan also significantly reduced in situ superoxide
      anion production, aortic expression of NF-kappaB and matrix metalloproteinase-9
      (MMP-9). In vitro treatment of RAW264.7 macrophages with Tan significantly
      suppressed oxidized LDL-induced reactive oxygen species production, pro
      inflammatory cytokine (IL-6, TNF-alpha, MCP-1) expression, and MMP-9 activity.
      Tan attenuates the development of atherosclerotic lesions and promotes plaque
      stability in ApoE(-/-) mice by reducing vascular oxidative stress and
      inflammatory response. Our findings highlight Tan as a potential therapeutic
      agent to prevent atherosclerotic cardiovascular diseases.

PMID- 21889488
TI  - The translocator protein (peripheral benzodiazepine receptor) mediates rat
      selective activation of the mitochondrial permeability transition by norbormide.
AB  - We have investigated the mechanism of rat-selective induction of the
      mitochondrial permeability transition (PT) by norbormide (NRB). We show that the
      inducing effect of NRB on the PT (i) is inhibited by the selective ligands of the
      18kDa outer membrane (OMM) translocator protein (TSPO, formerly peripheral
      benzodiazepine receptor) protoporphyrin IX, N,N-dihexyl-2-(4-fluorophenyl)indole
      3-acetamide and 7-chloro-5-(4-chlorophenyl)-1,3-dihydro-1-methyl-2H-1,4
      benzodiazepin-2-one; and (ii) is lost in digitonin mitoplasts, which lack an
      intact OMM. In mitoplasts the PT can still be induced by the NRB cationic
      derivative OL14, which contrary to NRB is also effective in intact mitochondria
      from mouse and guinea pig. We conclude that selective NRB transport into rat
      mitochondria occurs via TSPO in the OMM, which allows its translocation to PT
      regulating sites in the inner membrane. Thus, species-specificity of NRB toward
      the rat PT depends on subtle differences in the structure of TSPO or of TSPO
      associated proteins affecting its substrate specificity.

PMID- 21889490
TI  - Compatible solutes: ectoine and hydroxyectoine improve functional nanostructures
      in artificial lung surfactants.
AB  - Ectoine and hydroxyectoine belong to the family of compatible solutes and are
      among the most abundant osmolytes in nature. These compatible solutes protect
      biomolecules from extreme conditions and maintain their native function. In the
      present study, we have investigated the effect of ectoine and hydroxyectoine on
      the domain structures of artificial lung surfactant films consisting of
      dipalmitoylphosphatidylcholine (DPPC), dipalmitoylphosphatidylglycerol (DPPG) and
      the lung surfactant specific surfactant protein C (SP-C) in a molar ratio of
      80:20:0.4. The pressure-area isotherms are found to be almost unchanged by both
      compatible solutes. The topology of the fluid domains shown by scanning force
      microscopy, which is thought to be responsible for the biophysical behavior under
      compression, however, is modified giving rise to the assumption that ectoine and
      hydroxyectoine are favorable for a proper lung surfactant function. This is
      further evidenced by the analysis of the insertion kinetics of lipid vesicles
      into the lipid-peptide monolayer, which is clearly enhanced in the presence of
      both compatible solutes. Thus, we could show that ectoine and hydroxyectoine
      enhance the function of lung surfactant in a simple model system, which might
      provide an additional rationale to inhalative therapy.

PMID- 21889489
TI  - Expression, purification, electron microscopy, N-glycosylation mutagenesis and
      molecular modeling of human P2X4 and Dictyostelium discoideum P2XA.
AB  - The recent publication of the apo-, closed-state 3D crystal structure of
      zebrafish (zf) P2X4.1 has not only revolutionized the P2X research field, but
      also highlighted the need for further crystal structures, of receptors in
      different activation states, so that we can gain a complete molecular
      understanding of ion channel function. zfP2X4.1 was selected as a 3D
      crystallization candidate because of its ability to form stable trimers in
      detergent solution, and purified from over-expression in baculovirus-infected
      Spodoptera frugiperda (Sf9) insect cells. In this work, we have used a similar
      approach to express both human P2X4 (hP2X4) and Dictyostelium discoideum P2XA
      (DdP2XA) in Sf9 cells. Although hP2X4 did not form stable trimers in detergent
      solution, both receptors bound to ATP-coupled resins, indicating that their
      extracellular domains were folded correctly. DdP2XA formed strong trimers in
      detergent solution, and we were able to selectively purify trimers using
      preparative electrophoresis, and build a 21A-resolution 3D structure using
      transmission electron microscopy and single particle analysis. Although the
      structure of DdP2XA possessed similar dimensions to those of the previously
      determined low-resolution hP2X4 structure and the zfP2X4.1 crystal structure, N
      glycosylation mutagenesis and molecular modeling indicated differences between N
      glycan usage and predicted accessibility in models of DdP2XA based on the
      zfP2X4.1 crystal structure. Our data demonstrate that DdP2XA expressed in insect
      cells retains ATP-binding capacity after detergent solubilization, is an ideal
      candidate for structural study, and possesses a significantly different 3D
      structure to that of both hP2X4 and zfP2X4.1.

PMID- 21889491
TI  - Correlation between the ripple phase and stripe domains in membranes.
AB  - We investigate the relationship between stripe domains and the ripple phase in
      membranes. These have previously been observed separately without being linked
      explicitly. Past results have demonstrated that solid and ripple phases exhibit
      rich textural patterns related to the orientational order of tilted lipids and
      the orientation of ripple corrugations. Here we reveal a highly complex network
      pattern of ripple and solid domains in DLPC, DPPC bilayers with structures
      covering length scales from 10 nm to 100 MUm. Using spincoated double supported
      membranes we investigate domains by correlated AFM and fluorescence microscopy.
      Cooling experiments demonstrate the mode of nucleation and growth of stripe
      domains enriched in the fluorescent probe. Concurrent AFM imaging reveals that
      these stripe domains have a one-to-one correspondence with a rippled morphology
      running parallel to the stripe direction. Both thin and thick stripe domains are
      observed having ripple periods of 13.5+/-0.2 nm and 27.4+/-0.6 nm respectively.
      These are equivalent to previously observed asymmetric/equilibrium and
      symmetric/metastable ripple phases, respectively. Thin stripes grow from small
      solid domains and grow predominantly in length with a speed of ~3 times that of
      the thick stripes. Thick stripes grow by templating on the sides of thinner
      stripes or can emerge directly from the fluid phase. Bending and branching angles
      of stripes are in accordance with an underlying six fold lattice. We discuss
      mechanisms for the nucleation and growth of ripples and discuss a generic phase
      diagram that may partly rationalize the coexistence of metastable and stable
      phases.

PMID- 21889492
TI  - The tricyclic antidepressant imipramine induces autophagic cell death in U-87MG
      glioma cells.
AB  - In this study, we investigated the antitumor effects of the tricyclic
      antidepressant 3-(10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)-N,N-dimethylpropan-1
      amine (imipramine) on glioma cells. We found that exposure of U-87MG cells to
      imipramine resulted in the inhibition of PI3K/Akt/mTOR signaling, reduction of
      clonogenicity, and induction of cell death. Imipramine stimulated the formation
      of acidic vesicular organelles, the conversion of LC3-I to LC3-II, and the
      redistribution of LC3 to autophagosomes, suggesting that it stimulates the
      progression of autophagy. It did not, however, induce apoptosis. We further
      showed that knockdown of Beclin-1 using siRNA abrogated imipramine-induced cell
      death. These results suggest that imipramine exerts antitumor effects on PTEN
      null U-87MG human glioma cells by inhibiting PI3K/Akt/mTOR signaling and by
      inducing autophagic cell death.

PMID- 21889493
TI  - Role of metabolism by the human intestinal microflora in arbutin-induced
      cytotoxicity in HepG2 cell cultures.
AB  - A possible role for metabolism by the human intestinal microflora in arbutin
      induced cytotoxicity was investigated using human hepatoma HepG2 cells. When the
      cytotoxic effects of arbutin and hydroquinone (HQ), a deglycosylated metabolite
      of arbutin, were compared, HQ was more toxic than arbutin. Incubation of arbutin
      with a human fecal preparation could produce HQ. Following incubation of arbutin
      with a human fecal preparation for metabolic activation, the reaction mixture was
      filter-sterilized to test its toxic effects on HepG2 cells. The mixture induced
      cytotoxicity in HepG2 cells in a concentration-dependent manner. In addition, the
      mixture considerably inhibited expression of Bcl-2 together with an increase in
      Bax expression. Likewise, activation stimulated cleavage of caspase-3 and
      production of reactive oxygen species in HepG2 cell cultures. Furthermore,
      induction of apoptosis by the intestinal microflora reaction mixture was
      confirmed by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick
      end labeling assay. Taken together, these findings suggest that the human
      intestinal microflora is capable of metabolizing arbutin to HQ, which can induce
      apoptosis in mammalian cells.

PMID- 21889494
TI  - Sir-2.1 modulates 'calorie-restriction-mediated' prevention of neurodegeneration
      in Caenorhabditis elegans: implications for Parkinson's disease.
AB  - The phenomenon of aging is known to modulate many disease conditions including
      neurodegenerative ailments like Parkinson's disease (PD) which is characterized
      by selective loss of dopaminergic neurons. Recent studies have reported on such
      effects, as calorie restriction, in modulating aging in living systems. We reason
      that PD, being an age-associated neurodegenerative disease might be modulated by
      interventions like calorie restriction. In the present study we employed the
      transgenic Caenorhabditis elegans model (P(dat-1)::GFP) expressing green
      fluorescence protein (GFP) specifically in eight dopaminergic (DA) neurons.
      Selective degeneration of dopaminergic neurons was induced by treatment of worms
      with 6-hydroxy dopamine (6-OHDA), a selective catecholaminergic neurotoxin,
      followed by studies on effect of calorie restriction on the neurodegeneration.
      Employing confocal microscopy of the dopaminergic neurons and HPLC analysis of
      dopamine levels in the nematodes, we found that calorie restriction has a
      preventive effect on dopaminergic neurodegeneration in the worm model. We further
      studied the role of sirtuin, sir-2.1, in modulating such an effect. Studies
      employing RNAi induced gene silencing of nematode sir-2.1, revealed that presence
      of Sir-2.1 is necessary for achieving the protective effect of calorie
      restriction on dopaminergic neurodegeneration. Our studies provide evidence that
      calorie restriction affords, an sir-2.1 mediated, protection against the
      dopaminergic neurodegeneration, that might have implications for
      neurodegenerative Parkinson's disease.

PMID- 21889495
TI  - The MUC4 membrane-bound mucin regulates esophageal cancer cell proliferation and
      migration properties: Implication for S100A4 protein.
AB  - MUC4 is a membrane-bound mucin known to participate in tumor progression. It has
      been shown that MUC4 pattern of expression is modified during esophageal
      carcinogenesis, with a progressive increase from metaplastic lesions to
      adenocarcinoma. The principal cause of development of esophageal adenocarcinoma
      is the gastro-esophageal reflux, and MUC4 was previously shown to be upregulated
      by several bile acids present in reflux. In this report, our aim was thus to
      determine whether MUC4 plays a role in biological properties of human esophageal
      cancer cells. For that stable MUC4-deficient cancer cell lines (shMUC4 cells)
      were established using a shRNA approach. In vitro (proliferation, migration and
      invasion) and in vivo (tumor growth following subcutaneous xenografts in SCID
      mice) biological properties of shMUC4 cells were analyzed. Our results show that
      shMUC4 cells were less proliferative, had decreased migration properties and did
      not express S100A4 protein when compared with MUC4 expressing cells. Absence of
      MUC4 did not impair shMUC4 invasiveness. Subcutaneous xenografts showed a
      significant decrease in tumor size when cells did not express MUC4. Altogether,
      these data indicate that MUC4 plays a key role in proliferative and migrating
      properties of esophageal cancer cells as well as is a tumor growth promoter. MUC4
      mucin appears thus as a good therapeutic target to slow-down esophageal tumor
      progression.

PMID- 21889496
TI  - Regioselectivity of human UDP-glucuronosyltransferase isozymes in flavonoid
      biotransformation by metal complexation and tandem mass spectrometry.
AB  - Based on reactions with five flavonoids, the regioselectivities of twelve human
      UDP-glucuronosyltransferase (UGT) isozymes were elucidated. The various flavonoid
      glucuronides were differentiated based on LC-MS/MS fragmentation patterns of
      [Co(II)(flavonoid-H)(4,7-diphenyl-1,10-phenanthroline)(2)](+) complexes generated
      upon post-column complexation. Glucuronide distributions were evaluated to allow
      a systematic assessment of the regioselectivity of each isozyme. The various UGT
      enzymes, including eight UGT1A and four UGT2B, displayed a remarkable range of
      selectivities, both in terms of the positions of glucuronidation and relative
      reactivity with flavanones versus flavonols.

PMID- 21889497
TI  - Combating enterovirus replication: state-of-the-art on antiviral research.
AB  - Enteroviruses form an important genus within the large family of Picornaviridae.
      They are small, non-enveloped (+)RNA viruses, many of which are important
      pathogens in human and veterinary science. Despite their huge medical and socio
      economical impact, there is still no approved antiviral therapy at hand for the
      treatment of these infections. Three capsid-targeting molecules (pleconaril, BTA
      798 and V-073) are in clinical development. Pleconaril and BTA-798 are in phase
      II clinical trials for the treatment of enterovirus-induced sepsis syndrome and
      rhinovirus-induced aggravation of pre-existing asthma or COPD respectively. V-073
      is in preclinical development for the treatment of poliovirus infections in the
      context of the worldwide polio eradication program. The capsid binding molecules
      have shown good in vitro potency against a number of enterovirus species, but
      lack activity against others. Another potential drawback of capsid inhibitors in
      the clinical setting could be the rapid emergence of drug resistance. It will
      therefore be important to develop inhibitors that affect other stages in the
      viral replication cycle. Several viral proteins, such as the viral 3C protease,
      the putative 2C helicase and the 3D RNA-dependent RNA polymerase may be/are
      excellent targets for inhibition of viral replication. Also host cell factors
      that are crucial in viral replication may be considered as potential targets for
      an antiviral approach. Unraveling these complex virus-host interactions will also
      provide better insights into the replication of enteroviruses. This review aims
      to summarize and discuss known inhibitors and potential viral and cellular
      targets for antiviral therapy against enteroviruses.

PMID- 21889498
TI  - Molecular analysis of ABCD1 gene in Indian patients with X-linked
      adrenoleukodystrophy.
AB  - BACKGROUND: X-linked Adrenoleukodystrophy (X-ALD), with an incidence of 1:14,000
      is the most frequent monogenic demyelinating disorder worldwide. The principal
      biochemical abnormality in X-ALD is the increased levels of saturated, unbranched
      very long chain fatty acids (VLCFA). It is caused by mutations in ABCD1 gene. No
      molecular data on X-ALD is available in India and mutational spectrum in Indian
      patients is not known. METHODS: We standardized conformation sensitive gel
      electrophoresis (CSGE) method to detect mutations in ABCD1 gene in twenty Indian
      patients with X-ALD. The results were confirmed by sequencing. Genotype-phenotype
      correlation was also attempted. Prenatal diagnosis (PND) in one family was done
      using chorionic villi (CV) sample at 12 weeks of gestation. RESULTS: Out of
      twenty, causative mutations could be identified in twelve patients (60%). Six
      reported and four novel mutations were identified. Three polymorphisms were also
      observed. No hot spot was found. No significant genotype-phenotype correlation
      could be established. CONCLUSIONS: The study identified the mutation spectrum of
      Indian X-ALD patients, which enabled us to offer accurate genetic counseling,
      carrier detection and prenatal diagnosis where needed.

PMID- 21889499
TI  - Sample collection and handling considerations for peptidomic studies in whole
      saliva; implications for biomarker discovery.
AB  - BACKGROUND: Proteomic studies in saliva have demonstrated its potential as a
      diagnostic biofluid, however the salivary peptidome is less studied. Here we
      study the effects of several sample collection and handling factors on salivary
      peptide abundance levels. METHODS: Salivary peptides were isolated using an
      ultrafiltration device and analyzed by tandem mass spectrometry. A panel of 41
      peptides common after various treatments were quantified and normalized. We
      evaluated the effects of freezing rate of the samples, nutritional status of the
      donors (fed vs. fasted), and room-temperature sample degradation on peptide
      abundance levels. Repeatability of our sample processing method and our
      instrumental analysis method were investigated. RESULTS: Increased sample
      freezing rate produced higher levels of peptides. Donor nutritional status had no
      influence on the levels of measured peptides. No significant difference was
      detected in donors' saliva following 5, 10 and 15 min of room-temperature
      degradation. Sample processing and instrumental variability were relatively
      small, with median CVs of 9.6 and 6.6. CONCLUSIONS: Peptide abundance levels in
      saliva are rather forgiving towards variations in sample handling and donor
      nutritional status. Differences in freezing methods may affect peptide abundance,
      so consistency in freezing samples is preferred. Our results are valuable for
      standardizing sample collection and handling methods for peptidomic-based
      biomarker studies in saliva.

PMID- 21889500
TI  - Inosine 5'-monophosphate dehydrogenase activity as a biomarker in the field of
      transplantation.
AB  - Inosine 5'monophosphate dehydrogenase (IMPDH) is the rate limiting enzyme in the
      de novo synthesis of guanine nucleotides. The direct determination of target
      enzyme activity as a biomarker of mycophenolic acid (MPA) may help to estimate
      better the individual response to the immunosuppressant. However, the assessment
      of the clinical utility of this approach is limited by the diversity of the assay
      systems, which has not yet allowed the prospective assessment of this enzyme in
      larger patient cohorts. A recently validated and standardized assay allows the
      investigation of IMPDH activity in larger clinical studies. Although descriptive
      results from observational studies hold promise for a more individualized therapy
      in transplant medicine, more studies are needed to prospectively validate this
      approach.

PMID- 21889501
TI  - Overexpression of UDP-GlcNAc transporter partially corrects galactosylation
      defect caused by UDP-Gal transporter mutation.
AB  - Nucleotide sugar transporters deliver substrates for glycosyltransferases into
      the endoplasmic reticulum and the Golgi apparatus. We demonstrated that
      overexpression of UDP-GlcNAc transporter (NGT) in MDCK-RCA(r) and CHO-Lec8 mutant
      cells defective in UDP-Gal transporter (UGT) restored galactosylation of N
      glycans. NGT overexpression resulted in decreased transport of UDP-GlcNAc into
      the Golgi vesicles. This effect resembled the phenotype of mutant cells corrected
      by UGT1 overexpression. The transport of UDP-Gal was not significantly changed.
      Our data suggest that the biological function of UGT and NGT in galactosylation
      of macromolecules may be coupled.

PMID- 21889502
TI  - The endogenous siRNA pathway in Drosophila impacts stress resistance and lifespan
      by regulating metabolic homeostasis.
AB  - Small non-coding RNAs regulate gene expression in a sequence-specific manner. In
      Drosophila, Dicer-2 (Dcr-2) functions in the biogenesis of endogenous small
      interfering RNAs (endo-siRNAs). We identified 21 distinct proteins that exhibited
      a >= 1.5-fold change as a consequence of loss of dcr-2 function. Most of these
      were metabolic genes implicated in stress resistance and aging. dcr-2 Mutants had
      reduced lifespan and were hypersensitive to oxidative, endoplasmic reticulum,
      starvation, and cold stresses. Furthermore, loss of dcr-2 function led to
      abnormal lipid and carbohydrate metabolism. Our results suggest roles for the
      endo-siRNA pathway in metabolic regulation and defense against stress and aging
      in Drosophila.

PMID- 21889503
TI  - The cytochrome f-plastocyanin complex as a model to study transient interactions
      between redox proteins.
AB  - Transient complexes, with a lifetime ranging between microseconds and seconds,
      are essential for biochemical reactions requiring a fast turnover. That is the
      case of the interactions between proteins engaged in electron transfer reactions,
      which are involved in relevant physiological processes such as respiration and
      photosynthesis. In the latter, the copper protein plastocyanin acts as a soluble
      carrier transferring electrons between the two membrane-embedded complexes
      cytochrome b(6)f and photosystem I. Here we review the combination of
      experimental efforts in the literature to unveil the functional and structural
      features of the complex between cytochrome f and plastocyanin, which have widely
      been used as a suitable model for analyzing transient redox interactions.

PMID- 21889504
TI  - Conformations of the Huntingtin N-term in aqueous solution from atomistic
      simulations.
AB  - The first 17 amino acids of Huntingtin protein (N17) play a crucial role in the
      protein's aggregation. Here we predict its free energy landscape in aqueous
      solution by using bias exchange metadynamics. All our findings are consistent
      with experimental data. N17 populates four main kinetic basins, which
      interconvert on the microsecond time-scale. The most populated basin (about 75%)
      is a random coil, with an extended flat exposed hydrophobic surface. This might
      create a hydrophobic seed promoting Huntingtin aggregation. The other main
      populated basins contain helical conformations, which could facilitate N17
      binding on its cellular targets.

PMID- 21889505
TI  - Role of microglia in CNS inflammation.
AB  - There is increasing confusion about the meaning of the terms inflammation,
      neuroinflammation, and microglial inflammation. We aim in this review to achieve
      greater clarity regarding these terms, which are essential for our understanding
      of the role of microglia in CNS inflammatory conditions. The important concept of
      sterile inflammation is explained against the backdrop of classical inflammation,
      and its key differences from what researchers refer to when they use the terms
      neuroinflammation and microglial inflammation are illustrated. We propose to
      replace the term "neuroinflammation" with "microglial activation" or "CNS pseudo
      inflammation", if microglial activation does not suffice. In addition, we
      recommend abandoning the terms "microglial inflammation" and "inflamed microglia"
      because of the lack of a clear concept behind them.

PMID- 21889506
TI  - Cytochrome c oxidase: Intermediates of the catalytic cycle and their energy
      coupled interconversion.
AB  - Several issues relevant to the current studies of cytochrome c oxidase catalytic
      mechanism are discussed. The following points are raised. (1) The terminology
      currently used to describe the catalytic cycle of cytochrome oxidase is outdated
      and rather confusing. Presumably, it would be revised so as to share nomenclature
      of the intermediates with other oxygen-reactive heme enzymes like P450 or
      peroxidases. (2) A "catalytic cycle" of cytochrome oxidase involving complete
      reduction of the enzyme by 4 electrons followed by oxidation by O(2) is a chimera
      composed artificially from two partial reactions, reductive and oxidative phases,
      that never operate together as a true multi-turnover catalytic cycle. The 4e(-)
      reduction-oxidation cycle would not serve a paradigm for oxygen reduction
      mechanism and protonmotive function of cytochrome oxidase. (3) The foremost role
      of the K-proton channel in the catalytic cycle may consist in securing faultless
      delivery of protons for heterolytic O-O bond cleavage in the oxygen-reducing
      site, minimizing the danger of homolytic scission reaction route. (4)
      Protonmotive mechanism of cytochrome oxidase may vary notably for the different
      single-electron steps in the catalytic cycle.

PMID- 21889507
TI  - Evolution of Cryptosporidium in vitro culture.
AB  - This overview discusses findings from culturing Cryptosporidium spp. in cell and
      axenic cultures as well as factors limiting the development of this parasite in
      cultivation systems during recent years. A systematic review is undertaken of
      findings regarding the life cycle of the parasite, taking into account
      physiological, biochemical and genetic aspects, in the hope that this attempt
      will facilitate future approaches to research and developments in the
      understanding of Cryptosporidium biology.

PMID- 21889509
TI  - The search for the missing link: a relic plastid in Perkinsus?
AB  - Perkinsus marinus (Phylum Perkinsozoa) is a protozoan parasite that has
      devastated natural and farmed oyster populations in the USA, significantly
      affecting the shellfish industry and the estuarine environment. The other two
      genera in the phylum, Parvilucifera and Rastrimonas, are parasites of
      microeukaryotes. The Perkinsozoa occupies a key position at the base of the
      dinoflagellate branch, close to its divergence from the Apicomplexa, a clade that
      includes parasitic protista, many harbouring a relic plastid. Thus, as a taxon
      that has also evolved toward parasitism, the Perkinsozoa has attracted the
      attention of biologists interested in the evolution of this organelle, both in
      its ultrastructure and the conservation, loss or transfer of its genes. A review
      of the recent literature reveals mounting evidence in support of the presence of
      a relic plastid in P. marinus, including the presence of multimembrane
      structures, characteristic metabolic pathways and proteins with a bipartite N
      terminal extension. Further, these findings raise intriguing questions regarding
      the potential functions and unique adaptation of the putative plastid and/or
      plastid genes in the Perkinsozoa. In this review we analyse the above-mentioned
      evidence and evaluate the potential future directions and expected benefits of
      addressing such questions. Given the rapidly expanding molecular/genetic
      resources and methodological toolbox for Perkinsus spp., these organisms should
      complement the currently established models for investigating plastid evolution
      within the Chromalveolata.

PMID- 21889508
TI  - Polymorphism associated with the Schistosoma mansoni tetraspanin-2 gene.
AB  - A vaccine against schistosomiasis would contribute significantly to reducing the
      3-70 million disability-adjusted life years lost annually to the disease. Towards
      this end, inoculation with the large extracellular loop (EC-2) of Schistosoma
      mansoni tetraspanin-2 protein (Sm-TSP-2) has proved effective in reducing worm
      and egg burdens in S. mansoni-infected mice. The EC-2 loop of Schistosoma
      japonicum TSP-2, however, has been found to be highly polymorphic, perhaps
      diminishing the likelihood that this antigen can be used for vaccination against
      this species. Here, we examine polymorphism of the EC-2 of Sm-TSP-2 in
      genetically unique worms derived from six individuals from Kisumu, Kenya.

PMID- 21889510
TI  - A new model for the estimation of cell proliferation dynamics using CFSE data.
AB  - CFSE analysis of a proliferating cell population is a popular tool for the study
      of cell division and divisionlinked changes in cell behavior. Recently Banks et
      al. (2011), Luzyanina et al. (2009), Luzyanina et al. (2007), a partial
      differential equation (PDE) model to describe lymphocyte dynamics in a CFSE
      proliferation assay was proposed. We present a significant revision of this model
      which improves the physiological understanding of several parameters. Namely, the
      parameter used previously as a heuristic explanation for the dilution of CFSE dye
      by cell division is replaced with a more physical component, cellular
      autofluorescence. The rate at which label decays is also quantified using a
      Gompertz decay process. We then demonstrate a revised method of fitting the model
      to the commonly used histogram representation of the data. It is shown that these
      improvements result in a model with a strong physiological basis which is fully
      capable of replicating the behavior observed in the data.

PMID- 21889512
TI  - Development of a high-sensitivity latex reagent for the detection of C-reactive
      protein.
AB  - Various convenient and high-sensitivity immunoassays based on luminescent oxygen
      channeling and chromatographic techniques have been developed in recent years.
      This study focused on the latex agglutination immunoassay because it is a simple,
      homogenous immunoassay, which is also cost effective. We developed a highly
      sensitive latex reagent and examined the method of antibody conjugation on the
      latex particle surface. We introduced spacer amino acids in the latex surface to
      investigate the relationship between the amino acid spacer and the binding of an
      anti-C-reactive protein (anti-CRP) antibody as well as to investigate the
      resulting reactivity of the latex reagent to antigen. Because the distance
      between the latex particle and the antibody is equal in each case, differences in
      immunoreactivity are attributed to the structure of the amino acid side chain
      (R). Thus, reactivity of the latex reagent depends on the inorganicity and
      organicity of R. We suggest that a useful amino acid spacer has an inorganicity
      to-organicity ratio of approximately 2.

PMID- 21889511
TI  - An improved cell isolation method for flow cytometric and functional analyses of
      cutaneous wound leukocytes.
AB  - Isolation of leukocytes from full-thickness excisional wounds has proven to be a
      difficult process that results in poor cell yield and holds significant
      limitations for functional assays. Given the increased interest in the isolation,
      characterization and functional measurements of wound-derived cell populations,
      herein we describe a method for preparing wound cell suspensions with an improved
      yield that enables both phenotypic and functional assessments.

PMID- 21889513
TI  - Rapid isolation of nuclei from living immune cells by a single centrifugation
      through a multifunctional lysis gradient.
AB  - Due to their low protein content and limited nuclear detergent stability, primary
      human immune cells such as monocytes or T lymphocytes represent a great challenge
      for standard nuclear isolation protocols. Nuclei clumping during the multiple
      centrifugation steps or contamination of isolated nuclei with cytoplasmic
      proteins due to membrane lysis is a frequently observed problem. Here we describe
      a versatile and novel method for the isolation of clean and intact nuclei from
      primary human monocytes, which can be applied for virtually any cell type. Living
      cells were applied on an iso-osmolar discontinuous iodixanol-based density
      gradient including a detergent-containing lysis layer. Mild cell lysis as well as
      efficient washing of the nuclei was performed during the course of one single low
      g-force centrifugation step. The isolation procedure, which we call lysis
      gradient centrifugation (LGC), results in the recovery of 90-95% of highly pure
      nuclei. This easy and highly reproducible procedure allows an effective
      preparation of nuclei and the cytoplasm in only 15 min with the ability to handle
      as little as one million cells per sample and easy parallel processing of
      multiple samples.

PMID- 21889514
TI  - S100B-RAGE dependent VEGF secretion by cardiac myocytes induces myofibroblast
      proliferation.
AB  - Post-infarct remodeling is associated with the upregulation of the receptor for
      advanced glycation end products (RAGE), the induction of its ligand the calcium
      binding protein S100B and the release of the potent endothelial-cell specific
      mitogen vascular endothelial growth factor (VEGF). To determine a possible
      functional interaction between S100B, RAGE and VEGF we stimulated rat neonatal
      cardiac myocyte cultures transfected with either RAGE or a dominant-negative
      cytoplasmic deletion mutant of RAGE with S100B for 48 h. Under baseline
      conditions, cardiac myocytes express low levels of RAGE and VEGF and secrete VEGF
      in the medium as measured by ELISA. In RAGE overexpressing myocytes, S100B (100
      nM) resulted in increases in VEGF mRNA, VEGF protein, VEGF secretion, and
      activation of the transcription factor NF-kappaB. Pre-treatment of RAGE
      overexpressing myocytes with the NF-kappaB inhibitor caffeic acid phenethyl ester
      inhibited increases in VEGF mRNA, VEGF protein and VEGF in the medium by S100B.
      In myocytes expressing dominant-negative RAGE, S100B did not induce VEGF mRNA,
      VEGF protein, VEGF secretion or NF-kappaB activation. In culture, rat neonatal
      and adult cardiac fibroblasts undergo phenotypic transition to myofibroblasts.
      Treatment of neonatal and adult myofibroblasts with VEGF (10 ng/mL) induces VEGFR
      2 (flk-1/KDR) tyrosine kinase phosphorylation, ERK1/2 phosphorylation and
      myofibroblast proliferation. Together these data demonstrate that secreted VEGF
      by cardiac myocytes in response to S100B via RAGE ligation induces myofibroblast
      proliferation potentially contributing to scar formation observed in infarcted
      myocardium. This article is part of a Special Issue entitled "Local Signaling in
      Myocytes".

PMID- 21889516
TI  - Nandrolone and resistance training induce heart remodeling: role of fetal genes
      and implications for cardiac pathophysiology.
AB  - AIMS: This study was conducted to assess the isolated and combined effects of
      nandrolone and resistance training on cardiac morphology, function, and mRNA
      expression of pathological cardiac hypertrophy markers. MAIN METHODS: Wistar rats
      were randomly divided into four groups and submitted to 6 weeks of treatment with
      nandrolone and/or resistance training. Cardiac parameters were determined by
      echocardiography. Heart was analyzed for collagen infiltration. Real-time RT-PCR
      was used to assess the pathological cardiac hypertrophy markers. KEY FINDINGS:
      Both resistance training and nandrolone induced cardiac hypertrophy. Nandrolone
      increased the cardiac collagen content, and reduced the cardiac index in non
      trained and trained groups, when compared with the respective vehicle-treated
      groups. Nandrolone reduced the ratio of maximum early to late transmitral flow
      velocity in non-trained and trained groups, when compared with the respective
      vehicle-treated groups. Nandrolone reduced the alpha-myosin heavy chain gene
      expression in both non-trained and trained groups, when compared with the
      respective vehicle-treated groups. Training reduced the beta-myosin heavy chain
      gene expression in the groups treated with vehicle and nandrolone. Only the
      association between training and nandrolone increased the expression of the
      skeletal alpha-actin gene and atrial natriuretic peptide in the left ventricle.
      SIGNIFICANCE: This study indicated that nandrolone, whether associated with
      resistance training or not, induces cardiac hypertrophy, which is associated with
      enhanced collagen content, re-expression of fetal genes the in left ventricle,
      and impaired diastolic and systolic function.

PMID- 21889515
TI  - Statistical potentials for hairpin and internal loops improve the accuracy of the
      predicted RNA structure.
AB  - RNA is directly associated with a growing number of functions within the cell.
      The accurate prediction of different RNA higher-order structures from their
      nucleic acid sequences will provide insight into their functions and molecular
      mechanics. We have been determining statistical potentials for a collection of
      structural elements that is larger than the number of structural elements
      determined with experimentally determined energy values. The experimentally
      derived free energies and the statistical potentials for canonical base-pair
      stacks are analogous, demonstrating that statistical potentials derived from
      comparative data can be used as an alternative energetic parameter. A new
      computational infrastructure-RNA Comparative Analysis Database (rCAD)-that
      utilizes a relational database was developed to manipulate and analyze very large
      sequence alignments and secondary-structure data sets. Using rCAD, we determined
      a richer set of energetic parameters for RNA fundamental structural elements
      including hairpin and internal loops. A new version of RNAfold was developed to
      utilize these statistical potentials. Overall, these new statistical potentials
      for hairpin and internal loops integrated into the new version of RNAfold
      demonstrated significant improvements in the prediction accuracy of RNA secondary
      structure.

PMID- 21889517
TI  - Identification and functional analyses of polymorphism haplotypes of protein
      phosphatase 2A-Aalpha gene promoter.
AB  - The serine-threonine protein phosphatase 2A (PP2A) is a heterotrimeric enzyme
      family that plays an essential regulatory role in cell growth, differentiation,
      and apoptosis. Mutations in the genes encoding PP2A-Aalpha/beta subunits are
      associated with tumorigenesis and other human diseases. To explore whether
      genetic variations in the promoter region of the PP2A-Aalpha gene (PPP2R1A) and
      their frequent haplotypes in the Han Chinese population have an impact on
      transcriptional activity, we collected DNA samples from 63 healthy Chinese donors
      and searched for genetic variations in the 5'-flanking promoter region of PPP2R1A
      (PPP2R1Ap). Haplotypes were characterized by Haploview analysis and individual
      subcloning. A set of molecular and functional experiments was performed using
      reporter genes and electrophoretic mobility shifting assay (EMSA). Seven genetic
      variations were identified within the promoter locus (2038bp) of PPP2R1A. Linkage
      disequilibrium (LD) patterns and haplotype profiles were analyzed using the
      identified genetic variants. Using serially truncated human PPP2R1A promoter
      luciferase constructs, we found that a 685bp (-448nt to +237nt) fragment around
      the transcription start site (TSS) was the core promoter region. Individual
      subcloning revealed the existence of six haplotypes in this proximal promoter
      region of PPP2R1Ap. Using luciferase reporter assays, we found that different
      haplotypes bearing different variant alleles exhibit distinct promoter
      activities. The EMSA revealed that the -241 -/G variant influences DNA-protein
      interactions involving the transcription factor NF-kappaB, which may regulate the
      activity of the PPP2R1A proximal promoter. Our findings suggest that functional
      genetic variants in the proximal promoter of the PP2A-Aalpha gene and their
      haplotypes are critical in the regulation of transcriptional activation.

PMID- 21889518
TI  - The GABA system in anxiety and depression and its therapeutic potential.
AB  - In the regulation of behavior, the role of GABA neurons has been extensively
      studied in the circuit of fear, where GABA interneurons play key parts in the
      acquisition, storage and extinction of fear. Therapeutically, modulators of
      alpha(2)/alpha(3) GABA(A) receptors, such as TPA023, have shown clinical proof of
      concept as novel anxiolytics, which are superior to classical benzodiazepines by
      their lack of sedation and much reduced or absent dependence liability. In view
      of the finding that anxiety disorders and major depression share a GABAergic
      deficit as a common pathophysiology, the GABA hypothesis of depression has found
      increasing support. It holds that alpha(2)/alpha(3) GABA(A) receptor modulators
      may serve as novel antidepressants. Initial clinical evidence for this view comes
      from the significantly enhanced antidepressant therapeutic response when
      eszopicole, an anxiolytic/hypnotic acting preferentially on alpha(2)/alpha(3) and
      alpha(1) GABA(A) receptors, was coadministered with an antidepressant. This
      effect persisted even when sleep items were not considered. These initial results
      warrant efforts to profile selective alpha(2)/alpha(3) GABA(A) receptor
      modulators, such as TPA023, as novel antidepressants. In addition, GABA(B)
      receptor antagonists may serve as potential antidepressants. This article is part
      of a Special Issue entitled 'Anxiety and Depression'.

PMID- 21889519
TI  - The timing of feature-based attentional effects during object perception.
AB  - Allocating attention to basic features such as colour enhances perception of the
      respective features throughout the visual field. We have previously shown that
      feature-based attention also plays a role for more complex features required for
      object perception. To investigate at which level object perception is modulated
      by feature-based attention we recorded high-density event-related potentials
      (ERPs). Participants detected contour-defined objects or motion, and were
      informed to expect each feature dimension. Participants perceived contour-defined
      objects and motion better when they expected the congruent feature. This is
      consistent with modulation of the P1 when attending to lower-level features. For
      contours, modulation occurred at 290 ms, first at frontal electrodes and then at
      posterior sites, associated with sources in ventral visual areas accompanied by
      greater signal strength. This pattern of results is consistent with what has been
      observed in response to illusory contours. Our data provide novel insights into
      the contribution of feature-based attention to object perception that are
      associated with higher tier brain areas.

PMID- 21889520
TI  - Sensory and semantic category subdivisions within the anterior temporal lobes.
AB  - In the semantic memory literature the anterior temporal lobe (ATL) is frequently
      discussed as one homogeneous region when in fact, anatomical studies indicate
      that it is likely that there are discrete subregions within this area. Indeed,
      the influential Hub Account of semantic memory has proposed that this region is a
      sensory-amodal, general-purpose semantic processing region. However review of the
      literature suggested two potential demarcations: sensory subdivisions and a
      social/nonsocial subdivision. To test this, participants were trained to
      associate social or non-social words with novel auditory, visual, or audiovisual
      stimuli. Later, study participants underwent an fMRI scan where they were
      presented with the sensory stimuli and the task was to recall the semantic
      associate. The results showed that there were sensory specific subdivisions
      within the ATL - that the perceptual encoding of auditory stimuli preferentially
      activated the superior ATL, visual stimuli the inferior ATL, and multisensory
      stimuli the polar ATL. Moreover, our data showed that there is stimulus-specific
      sensitivity within the ATL - the superior and polar ATLs were more sensitive to
      the retrieval of social knowledge as compared to non-social knowledge. No ATL
      regions were more sensitive to the retrieval of non-social knowledge. These
      findings indicate that the retrieval of newly learned semantic associations
      activates the ATL. In addition, superior and polar aspects of the ATL are
      sensitive to social stimuli but relatively insensitive to non-social stimuli, a
      finding that is predicted by anatomical connectivity and single-unit studies in
      non-human primates. And lastly, the ATL contains sensory processing subdivisions
      that fall along superior (auditory), inferior (visual), polar (audiovisual)
      subdivisions.

PMID- 21889521
TI  - Area postrema lesions attenuate LiCl-induced c-Fos expression correlated with
      conditioned taste aversion learning.
AB  - Lesions of the area postrema (AP) block many of the behavioral and physiological
      effects of lithium chloride (LiCl) in rats, including formation of conditioned
      taste aversions (CTAs). Systemic administration of LiCl induces c-Fos
      immunoreactivity in several brain regions, including the AP, nucleus of the
      solitary tract (NTS), lateral parabrachial nucleus (latPBN), supraoptic nucleus
      (SON), paraventricular nucleus (PVN), and central nucleus of the amygdala (CeA).
      To determine which of these brain regions may be activated in parallel with the
      acquisition of LiCl-induced CTAs, we disrupted CTA learning in rats by ablating
      the AP and then quantified c-Fos-positive cells in these brain regions in sham-
      and AP-lesioned rats 1 h following LiCl or saline injection. Significant c-Fos
      induction after LiCl was observed in the CeA and SON of AP-lesioned rats,
      demonstrating activation independent of an intact AP. LiCl-induced c-Fos was
      significantly attenuated in the NTS, latPBN, PVN and CeA of AP-lesioned rats,
      suggesting that these regions are dependent on AP activation. Almost all of the
      lesioned rats showed some damage to the subpostremal NTS, and some rats also had
      damage to the dorsal motor nucleus of the vagus; this collateral damage in the
      brainstem may have contributed to the deficits in c-Fos response. Because c-Fos
      induction in several regions was correlated with magnitude of CTA acquisition,
      these regions are implicated in the central mediation of lithium effects during
      CTA learning.

PMID- 21889524
TI  - Successful acquisition of an olfactory discrimination test by Asian elephants,
      Elephas maximus.
AB  - The present study demonstrates that Asian elephants, Elephas maximus, can
      successfully be trained to cooperate in an olfactory discrimination test based on
      a food-rewarded two-alternative instrumental conditioning procedure. The animals
      learned the basic principle of the test within only 60 trials and readily
      mastered intramodal stimulus transfer tasks. Further, they were capable of
      distinguishing between structurally related odor stimuli and remembered the
      reward value of previously learned odor stimuli after 2, 4, 8, and 16 weeks of
      recess without any signs of forgetting. The precision and consistency of the
      elephants' performance in tests of odor discrimination ability and long-term odor
      memory demonstrate the suitability of this method for assessing olfactory
      function in this proboscid species. An across-species comparison of several
      measures of olfactory learning capabilities such as speed of initial task
      acquisition and ability to master intramodal stimulus transfer tasks shows that
      Asian elephants are at least as good in their performance as mice, rats, and
      dogs, and clearly superior to nonhuman primates and fur seals. The results
      support the notion that Asian elephants may use olfactory cues for social
      communication and food selection and that the sense of smell may play an
      important role in the control of their behavior.

PMID- 21889522
TI  - Corticotrophin releasing factor (CRF) induced reinstatement of cocaine seeking in
      male and female rats.
AB  - Significant sex differences have been demonstrated in clinical and preclinical
      studies of cocaine addiction, with some of the most consistent differences noted
      in regard to the role of stress and craving. The current study examined stress
      induced reinstatement of cocaine seeking in male and female rats in an animal
      model of relapse using corticotropin-releasing factor (CRF) administration. Both
      male and female rats demonstrated increased cocaine seeking in response to CRF.
      CRF-induced reinstatement was highly variable across both male and female rats,
      and further analysis revealed a subpopulation that was particularly sensitive to
      CRF (high responders). Female high responders displayed significantly increased
      responding to CRF compared to males. Individual differences in stress
      responsivity could thus contribute to the likelihood of relapse, with females
      showing greater heterogeneity to stress-induced relapse.

PMID- 21889523
TI  - Estradiol increases the anorexia associated with increased 5-HT(2C) receptor
      activation in ovariectomized rats.
AB  - Estradiol's inhibitory effect on food intake is mediated, in part, by its ability
      to increase the activity of meal-related signals, including serotonin (5-HT),
      which hastens satiation. The important role that postsynaptic 5-HT(2C) receptors
      play in mediating 5-HT's anorexigenic effect prompted us to investigate whether a
      regimen of acute estradiol treatment increases the anorexia associated with
      increased 5-HT(2C) receptor activation in ovariectomized (OVX) rats. We
      demonstrated that intraperitoneal and intracerebroventricular (i.c.v.)
      administration of low doses of the 5-HT(2C) receptor agonist meta
      chlorophenylpiperazine (mCPP) decreased 1-h dark-phase food intake in estradiol
      treated, but not oil-treated, OVX rats. During a longer feeding test, we
      demonstrated that i.c.v. administration of mCPP decreased 22-h food intake in oil
      treated and, to a greater extent, estradiol-treated OVX rats. In a second study,
      we demonstrated that estradiol increased 5-HT(2C) receptor protein content in the
      caudal brainstem, but not hypothalamus, of OVX rats. We conclude that a
      physiologically-relevant regimen of acute estradiol treatment increases
      sensitivity to mCPP's anorexigenic effect. Our demonstration that this same
      regimen of estradiol treatment increases 5-HT(2C) receptor protein content in the
      caudal hindbrain of OVX rats provides a possible mechanism to explain our
      behavioral findings.

PMID- 21889525
TI  - The effects of phencyclidine (PCP) on anxiety-like behavior in the elevated plus
      maze and the light-dark exploration test are age dependent, sexually dimorphic,
      and task dependent.
AB  - Previous research in our laboratory revealed sexually dimorphic effects of prior
      exposure to phencyclidine (PCP) on elevated plus maze behavior. In an attempt to
      examine the developmental time course of this effect and determine the extent to
      which it generalizes to other anxiety paradigms, young adult (61-64 days old) and
      adult (96-107 days old) male and female rats were treated with PCP (15 mg/kg) or
      saline. Following a two week withdrawal period, animals were tested in either the
      elevated plus maze (EPM) or a light-dark exploration (LD) test. In adults, both
      tests revealed a sexually dimorphic effect driven by PCP-induced decreases in
      anxiety in females as indicated by increased time spent in the open arms of the
      EPM and in the lit compartment of the LD test and increased anxiety in males as
      indicated by decreased time spent in the lit compartment of the LD. In young
      animals, PCP pretreatment decreased open arm exploration in the elevated plus
      maze, indicating increased anxiety. However, PCP increased time spent in the
      light compartment in the light-dark exploration test, indicating decreased
      anxiety. Corticosterone levels measured 15 min after the onset of the EPM failed
      to reveal an association between the behavioral effects of PCP and corticosterone
      levels. The results in adults substantiate the previously observed sexually
      dimorphic effect of PCP on elevated plus maze behavior in adults and indicate
      that the effect generalizes to another anxiety paradigm. The results in the
      younger animals suggest an age dependent effect of PCP on anxiety in general and
      indicate that behaviors in the elevated plus maze and the light-dark exploration
      test reflect dissociable psychobiological states.

PMID- 21889526
TI  - Antinociceptive effects of intragastric DL-tetrahydropalmatine on visceral and
      somatic persistent nociception and pain hypersensitivity in rats.
AB  - Although tetrahydropalmatine (THP), an alkaloid constituent of plants from the
      genera Stephania and Corydalis, is known to have analgesic property, the
      antinociceptive effects of THP have not been well evaluated experimentally and
      the appropriate indications for treatment of clinical pain remain unclear. In the
      present study, nociceptive and inflammatory models of both somatic and visceral
      origins were used to assess the antinociceptive and antihyperalgesic effects of
      intragastric (i.g.) pretreatment of dl-THP in rats. In the bee venom (BV) test
      that has been well established experimentally, i.g. pretreatment of three doses
      of dl-THP (20, 40, 60 mg/kg, body weight) resulted in less stably antinociceptive
      effect on the BV-induced persistent paw flinches that are known to be processed
      by spinal nociceptive circuit, however the drug of the two higher doses produced
      distinct suppression of the BV-induced persistent nociception rated by
      nociceptive score that reflects both spinal and supraspinal mediation. Similarly,
      the antinociception of dl-THP (60 mg/kg) was only significant for phase 1 but not
      for phase 2 of the formalin-induced persistent paw flinches, however, the
      inhibition was distinct for both phase 1 and phase 2 of the formalin nociceptive
      score. For the antihyperalgesic effect, in contrast, pretreatment of dl-THP (60
      mg/kg) produced significant inhibition of both primary hyperalgesia to either
      thermal or mechanical stimuli and the mirror-image thermal hyperalgesia
      identified in the BV test. In the acetic acid writhing test, the number of
      writhes was completely blocked at the first 5-min interval followed by a
      sustained suppression in the remaining period of the whole time course comparing
      to the vehicle control. These data suggest that i.g. pre-administration of dl-THP
      could more effectively inhibit visceral nociception as well as thermal and
      mechanical inflammatory pain hypersensitivity (hyperalgesia) than persistent
      nociception. Moreover, the drug is likely to produce more effectiveness on
      supraspinally processed nociceptive behaviors than spinally mediated nociceptive
      behaviors, implicating an action of THP at the supraspinal level.

PMID- 21889527
TI  - Promoting stair climbing in public-access settings: an audit of intervention
      opportunities in England.
AB  - OBJECTIVE: Introducing message prompts at the 'point-of-choice' (POC) between
      stairs and escalators increases stair choice in 'public-access' settings (e.g.
      malls). For nationwide campaigns, plentiful POCs appear needed. We audited the
      availability of POCs in public-access settings across England. METHODS:
      Boundaries for 25 urban areas (population=6,829,874) were verified using
      Ordinance Survey maps, which showed all airports and train/tram stations. Malls
      and bus stations were identified from commercial listings and local authority web
      pages. From September 2010-March 2011 two investigators visually inspected all
      venues (N=410), counting 'true' POCs and 'quasi' POCs (i.e. instances where
      stairs were visible from, but not adjacent to, escalators). RESULTS: 5% of venues
      had >=1 true POC (quasi POC=3%). Aggregating across areas, there was a true and
      quasi POC for every 243,924 and 379,437 people, respectively. There were regional
      variations; one area had 10 true/quasi POCs, whilst 10/24 remaining areas had
      none. POCs were more common in airports (4/6 venues) than malls (11/85) and train
      stations (4/215). CONCLUSION: Although public-access POCs reach sizeable
      audiences, their availability in England is sporadic, precluding nationwide
      campaigns. Interventions should be considered locally, based on available POCs.
      Work/community venues (e.g. offices, hospitals), where pedestrians choose between
      stairs and elevators, may provide greater intervention opportunities.

PMID- 21889528
TI  - Use of conventional care and complementary/alternative medicine among US adults
      with arthritis.
AB  - OBJECTIVE: Managing arthritis and co-morbid conditions is of public health
      importance. It is therefore critical to have a comprehensive understanding of
      healthcare utilization among US adults with arthritis. Thus, the present study
      identified characteristics associated with using both complementary and
      alternative medicine (CAM) and conventional healthcare. METHOD: Using 2007
      National Health Interview Survey data, multinomial logistic regression was
      performed to compare four categories of past year healthcare use (both CAM and
      conventional care vs. conventional care only, CAM only, and no healthcare use) on
      their potential correlates. RESULTS: The sample (n=3850) was 62.8% female and
      80.4% non-Hispanic White. Nearly half were at least 65 years old, and had used
      both CAM and conventional services in the previous year. The following
      characteristics were associated with having used neither CAM nor conventional
      care in the previous year (vs. having used both CAM and conventional care): being
      from an ethnic and racial minority group (ORs=2.44, 3.26, and 3.91) and being
      uninsured (OR=4.06), identifying individuals potentially at risk for unmet need.
      CONCLUSION: To ensure access to comprehensive care, potentially underserved
      populations should be targeted with outreach (e.g., providing low-cost,
      accessible care, and education about benefits of various treatments for arthritis
      and co-morbid conditions).

PMID- 21889529
TI  - Formulation optimization of chelerythrine loaded O-carboxymethylchitosan
      microspheres using response surface methodology.
AB  - The aims of this investigation were to develop a procedure to prepare
      chelerythrine (CHE) loaded O-carboxymethylchitosan (O-CMCS) microspheres by
      emulsion cross-linking method and optimize the process and formulation variables
      using response surface methodology (RSM) with a three-level, three-factor Box
      Behnken design (BBD). The independent variables studied were O-CMCS/CHE ratio,
      O/W phase ratio, and O-CMCS concentration, dependent variables (responses) were
      drug loading content and encapsulation efficiency. Mathematical equations and
      response surface plots were used to relate the dependent and independent
      variables. The process and formulation variables were optimized to achieve
      maximum drug loading content and entrapment efficiency by the desirability
      function. The optimized microsphere formulation was characterized for particle
      size, shape, morphology and in vitro drug release. Results for mean particle
      size, drug loading content, entrapment efficiency, and in vitro drug release of
      CHE-loaded O-CMCS microspheres were found to be of 12.18 MUm, 4.16 +/- 3.36%,
      57.40 +/- 2.30%, and 54.5% at pH 7.4 after 70 h, respectively. The combination
      use of RSM, BBD and desirability function could provide a promising application
      for O-CMCS as controlled drug delivery carrier and help to develop procedures for
      a lab-scale microemulsion process.

PMID- 21889530
TI  - Encapsulation of probiotic Bifidobacterium longum BIOMA 5920 with alginate-human
      like collagen and evaluation of survival in simulated gastrointestinal
      conditions.
AB  - Alginate (ALg)-human-like collagen (HLC) microspheres were prepared by the
      technology of electrostatic droplet generation in order to develop a
      biocompatible vehicle for probiotic bacteria. Microparticles were spherical with
      mean particle size of 400MUm. The encapsulation efficiency (EE) of ALg-HLC
      microspheres could reach 92-99.2%. Water-soluble and fibrous human-like collagen
      is combined with sodium alginate through intermolecular hydrogen bonding and
      electrostatic force which were investigated by Fourier transform infrared
      spectroscopy (FTIR) and differential scanning calorimetry (DSC), thus the matrix
      of ALg-HLC was very stable. Bifidobacterium longum BIOMA 5920, as a kind of
      probiotic bacteria, was encapsulated with alginate-human-like collagen to survive
      and function in simulated gastrointestinal juice. Microparticles were very easy
      to degradation in simulated intestinal juices. After incubation in simulated
      gastric (pH 2.0, 2h), the encapsulated B. longum BIOMA 5920 numbers were 4.81 +/-
      0.38 log cfu/g.

PMID- 21889532
TI  - X-ray structure of a galactose-specific lectin from Spatholobous parviflorous.
AB  - A galactose-specific seed lectin from Spatholobous parviflorus (SPL) has been
      purified, crystallized and its X-ray structure solved. It is the first lectin
      purified and crystallized from the genus Spatholobus (family: Fabaceae). The
      crystals belong to the space group P1, with a=60.792 A, b=60.998 A, c=78.179 A,
      alpha=78.68 degrees , beta=88.62 degrees , gamma=104.32 degrees . The data were
      collected at 2.04 A resolution under cryocondition, on a MAR image-plate detector
      system, mounted on a rotating anode X-ray generator. The coordinates of Dolichos
      biflorus lectin (1lu1) were successfully used for the structure solution by
      molecular replacement method. The primary structure of the SPL was not known
      earlier and it was unambiguously visible in the electron density. S. parviflorus
      lectin is a hetero-dimeric-tetramer with two alpha and two beta chains of 251 and
      239 residues respectively. SPL has two metal ions, Ca(2+) and Mn(2+), bound to a
      loop region of each chain. The SPL monomers are in jelly roll form.

PMID- 21889531
TI  - Molecular characterization and solution properties of enzymatically tailored
      arabinoxylans.
AB  - Two alpha-L-arabinofuranosidases with different substrate specificities were used
      to modify the arabinose-to-xylose ratio of cereal arabinoxylans: one enzyme (AXH
      m) removed the L-arabinofuranosyl substituents from the monosubstituted
      xylopyranosyl residues and the other (AXH-d3) the (1->3)-linked L
      arabinofuranosyl units from the disubstituted xylopyranosyl residue. In this
      study, we noticed that not only the arabinose-to-xylose ratio but also the
      position of the arabinofuranosyl substituents affects the water-solubility of
      arabinoxylans. The AXH-d3 treatment had no significant effect on the solution
      conformation of arabinoxylans, but the density of the arabinoxylan molecules
      decreased in DMSO solution after AXH-m modification. The possible heterogeneity
      of arabinoxylans complicated the interpretation of data describing the
      macromolecular properties of the enzymatically modified samples.

PMID- 21889533
TI  - Roles of hinge region, loops 3 and 4 in the activation of Escherichia coli cyclic
      AMP receptor protein.
AB  - The cAMP receptor protein (CRP) requires cAMP for an allosteric change and
      regulates more than 150 genes in Escherichia coli. In this study, the modular
      half of cAMP receptor protein was used to investigate the allosteric signal
      transmission pathway induced by cAMP binding. The activation of CRP upon cAMP
      binding is indicated to be realignment of the two subunits within the CRP dimer.
      The interaction of loop 3 and Phe136 do not involve in signal transmission.

PMID- 21889534
TI  - Mechanism of inhibition of arginine kinase by flavonoids consistent with
      thermodynamics of docking simulation.
AB  - Arginine kinase plays a vital role in invertebrate homeostasis by buffering ATP
      concentrations. Arginine kinase might serve as a target for environmentally
      friendly insect-selective pesticides, because it differs notably from its
      counterpart in vertebrates, creatine kinase. In this study, two members of the
      flavonoid family, quercetin (QU) and luteolin (LU), were identified as novel
      noncompetitive inhibitors of locust arginine kinase. They were found to have
      inhibition parameters (K(i)) of 11.2 and 23.9 MUM, respectively. By comparing
      changes in the activity and intrinsic fluorescence of AK, the inhibition
      mechanisms of these flavonoids were found to involve binding to Trp residues in
      the active site. This was determined by examination of the static quenching
      parameter K(sv). The main binding forces between flavonoids and AK were found to
      be hydrophobic based on the thermodynamic parameters of changes in enthalpy
      (DeltaH), entropy (DeltaS), and free energy (DeltaG) and on docking simulation
      results. Molecular docking analyses also suggested that flavonoids could bind to
      the active site of AK and were close to the Trp 221 in active site. Molecular
      simulation results mimic the experimental results, indicated that QU had a lower
      binding energy and a stronger inhibitory effect on AK than LU, suggesting that
      the extra hydroxyl group in QU might increase binding ability.

PMID- 21889536
TI  - Three-dimensional strain fields in human brain resulting from formalin fixation.
AB  - Before investigating human brains post mortem, the first preparation step is
      often formalin fixation of the brain. As the brain consists of inhomogeneous
      tissues, the fixation leads to a three-dimensional strain field within the
      tissue. During the single case MR-based investigation of the brain, first, the
      starting point with the brain post mortem but still within the cranium, was
      examined. Then 13 MR data sets were acquired over a fixation period of 70 days
      and compared to the initial data set. Based on affine registration of the data
      sets, the global volume shrinkage was found to be 8.1%. By means of a non-rigid
      registration additional maximal local volume strains of 32% were determined.

PMID- 21889535
TI  - Fish consumption and prenatal methylmercury exposure: cognitive and behavioral
      outcomes in the main cohort at 17 years from the Seychelles child development
      study.
AB  - INTRODUCTION: People worldwide depend upon daily fish consumption as a major
      source of protein and other nutrients. Fish are high in nutrients essential for
      normal brain development, but they also contain methylmercury (MeHg), a
      neurotoxicant. Our studies in a population consuming fish daily have indicated no
      consistent pattern of adverse associations between prenatal MeHg and children's
      development. For some endpoints we found performance improved with increasing
      prenatal exposure to MeHg. Follow up studies indicate this association is related
      to the beneficial nutrients present in fish. OBJECTIVES: To determine if the
      absence of adverse outcomes and the presence of beneficial associations between
      prenatal MeHg and developmental outcomes previously reported persists into
      adolescence. METHODS: This study was conducted on the Main Cohort of the
      Seychelles Child Development Study (SCDS). We examined the association between
      prenatal MeHg exposure and subjects' performance at 17 years of age on 27
      endpoints. The test battery included the Wisconsin Card Sorting Test (WCST), the
      California Verbal Learning Test (CVLT), the Woodcock-Johnson (W-J-II) Achievement
      Test, subtests of the Cambridge Neuropsychological Test Automated Battery
      (CANTAB), and measures of problematic behaviors. Analyses for all endpoints were
      adjusted for postnatal MeHg, sex, socioeconomic status, maternal IQ, and child's
      age at testing and the child's IQ was added for problematic behavioral endpoints.
      RESULTS: Mean prenatal MeHg exposure was 6.9 ppm. There was no association
      between prenatal MeHg and 21 endpoints. Increasing prenatal MeHg was associated
      with better scores on four endpoints (higher W-J-II math calculation scores,
      reduced numbers of trials on the Intra-Extradimensional Shift Set of the CANTAB),
      fewer reports of substance use and incidents of and referrals for problematic
      behaviors in school. Increasing prenatal MeHg was adversely associated with one
      level of referrals to a school counselor. CONCLUSIONS: At age 17 years there was
      no consistent pattern of adverse associations present between prenatal MeHg
      exposure and detailed domain specific neurocognitive and behavioral testing.
      There continues to be evidence of improved performance on some endpoints as
      prenatal MeHg exposure increases in the range studied, a finding that appears to
      reflect the role of beneficial nutrients present in fish as demonstrated
      previously in younger subjects. These findings suggest that ocean fish
      consumption during pregnancy is important for the health and development of
      children and that the benefits are long lasting.

PMID- 21889537
TI  - Evaluation of techniques used to estimate cortical feature maps.
AB  - Functional properties of neurons are often distributed nonrandomly within a
      cortical area and form topographic maps that reveal insights into neuronal
      organization and interconnection. Some functional maps, such as in visual cortex,
      are fairly straightforward to discern with a variety of techniques, while other
      maps, such as in auditory cortex, have resisted easy characterization. In order
      to determine appropriate protocols for establishing accurate functional maps in
      auditory cortex, artificial topographic maps were probed under various
      conditions, and the accuracy of estimates formed from the actual maps was
      quantified. Under these conditions, low-complexity maps such as sound frequency
      can be estimated accurately with as few as 25 total samples (e.g., electrode
      penetrations or imaging pixels) if neural responses are averaged together. More
      samples are required to achieve the highest estimation accuracy for higher
      complexity maps, and averaging improves map estimate accuracy even more than
      increasing sampling density. Undersampling without averaging can result in
      misleading map estimates, while undersampling with averaging can lead to the
      false conclusion of no map when one actually exists. Uniform sample spacing only
      slightly improves map estimation over nonuniform sample spacing typical of serial
      electrode penetrations. Tessellation plots commonly used to visualize maps
      estimated using nonuniform sampling are always inferior to linearly interpolated
      estimates, although differences are slight at higher sampling densities. Within
      primary auditory cortex, then, multiunit sampling with at least 100 samples would
      likely result in reasonable feature map estimates for all but the highest
      complexity maps and the highest variability that might be expected.

PMID- 21889538
TI  - Automated detection and analysis of neuronal persistent activity.
AB  - Cortical neurons receive individual as well as synchronized synaptic events. The
      latter may drive a neuron into an active state where a persistently depolarized
      membrane potential lasts for several seconds. Visual inspection and manual
      detection of these persistent events is labor-intensive. We built a set of
      scripts in MATLAB with the goal of having a core software package for the
      systematic and objective detection of persistent neural activity out of large
      time-series data. This analysis software includes multiple steps, from a pre
      processing stage, event detection, user-interactive detection reviewing, and
      filtering/graphing. Analysis scripts and brief usage information are freely
      available upon request.

PMID- 21889539
TI  - A bundled microwire array for long-term chronic single-unit recording in deep
      brain regions of behaving rats.
AB  - Chronic single-unit recording in subcortical brain regions is increasingly
      important in neurophysiological studies. However, methods for long-term, stable
      recording of multiple single-units in deep brain regions and in dura-surrounded
      ganglion have not yet been established. In the present study, we propose a
      bundled microwire array design which is capable of long-term recording of the
      trigeminal ganglion and deep-brain units. This electrode set is easy to construct
      from common materials and tools found in an electrophysiological laboratory. The
      salient features of our design include: (1) short and separated tungsten
      microwires for stable chronic recording; (2) the use of a 30-guage stainless
      steel guide tube for facilitating penetration and aiming for deep targets as well
      as electrical grounding; (3) the inclusion of a reference of the same microwire
      material inside the bundle to enhance common mode rejection of far field noises;
      and (4) an adjustable connector. In our case, we used a 90 degrees  backward
      bending connector so that implanted rats could perform the same hole-seeking
      behavior and their faces and the whiskers could be stimulated in the behaving
      state. It was demonstrated that this multi-channel electrode caused minimal
      tissue damage at the recording site and we were able to obtain good, stable
      single-unit recordings from the trigeminal ganglion and ventroposterior medial
      thalamus areas of freely moving rats for up to 80 days. This methodology is
      useful for the studies that require long term and high quality unit recording in
      the deep brain or in the trigeminal system.

PMID- 21889540
TI  - Rapid typing of influenza viruses using super high-speed quantitative real-time
      PCR.
AB  - The development of a rapid and sensitive system for detecting influenza viruses
      is a high priority for controlling future epidemics and pandemics. Quantitative
      real-time PCR is often used for detecting various kinds of viruses; however, it
      requires more than 2h per run. Detection assays were performed with super high
      speed RT-PCR (SHRT-PCR) developed according to a newly designed heating system.
      The new method uses a high-speed reaction (18s/cycle; 40 cycles in less than
      20min) for typing influenza viruses. The detection limit of SHRT-PCR was 1
      copy/reaction and 10(-1) plaque-forming unit/reaction for viruses in culture
      supernatants during 20min. Using SHRT-PCR, 86 strains of influenza viruses
      isolated by the Tokyo Metropolitan Institute of Public Health were tested; the
      results showed 100% sensitivity and specificity for each influenza A and B virus,
      and swine-origin influenza virus. Twenty-seven swabs collected from the
      pharyngeal mucosa of outpatients were also tested, showing positive signs for
      influenza virus on an immunochromatographic assay; the results between SHRT-PCR
      and immunochromatography exhibited 100% agreement for both positive and negative
      results. The rapid reaction time and high sensitivity of SHRT-PCR makes this
      technique well suited for monitoring epidemics and pre-pandemic influenza
      outbreaks.

PMID- 21889541
TI  - Antiviral activity of tenofovir against Cauliflower mosaic virus and its
      metabolism in Brassica pekinensis plants.
AB  - The antiviral effect of the acyclic nucleoside phosphonate tenofovir (R)-PMPA on
      double-stranded DNA Cauliflower mosaic virus (CaMV) in Brassica pekinensis plants
      grown in vitro on liquid medium was evaluated. Double antibody sandwich ELISA and
      PCR were used for relative quantification of viral protein and detecting nucleic
      acid in plants. (R)-PMPA at concentrations of 25 and 50 mg/l significantly
      reduced CaMV titers in plants within 6-9 weeks to levels detectable neither by
      ELISA nor by PCR. Virus-free plants were obtained after 3-month cultivation of
      meristem tips on semisolid medium containing 50 mg/l (R)-PMPA and their
      regeneration to whole plants in the greenhouse. Studying the metabolism of (R)
      PMPA in B. pekinensis revealed that mono- and diphosphate, structural analogs of
      NDP and/or NTP, are the only metabolites formed. The data indicate very low
      substrate activity of the enzymes toward (R)-PMPA as substrate. The extent of
      phosphorylation in the plant's leaves represents only 4.5% of applied labeled (R)
      PMPA. In roots, we detected no radioactive peaks of phosphorylated metabolites of
      (R)-PMPAp or (R)-PMPApp.

PMID- 21889542
TI  - Vesicular Stomatitis Virus glycoprotein G carrying a tandem dimer of Foot and
      Mouth Disease Virus antigenic site A can be used as DNA and peptide vaccine for
      cattle.
AB  - Effective Foot and Mouth Disease Virus (FMDV) peptide vaccines for cattle have
      two major constraints: resemblance of one or more of the multiple conformations
      of the major VP1 antigenic sites to induce neutralizing antibodies, and
      stimulation of T cells despite the variable bovine-MHC polymorphism. To overcome
      these limitations, a chimeric antigen was developed, using Vesicular Stomatitis
      Virus glycoprotein (VSV-G) as carrier protein of an in tandem-dimer of FMDV
      antigenic site A (ASA), the major epitope on the VP1 capsid protein (aa 139-149,
      FMDV-C3 serotype). The G-ASA construct was expressed in the Baculovirus system to
      produce a recombinant protein (DEL BAC) (cloned in pCDNA 3.1 plasmid) (Invitrogen
      Corporation, Carlsbad, CA) and was also prepared as a DNA vaccine (pC DEL).
      Calves vaccinated with both immunogens elicited antibodies that recognized the
      ASA in whole virion and were able to neutralize FMDV infectivity in vitro. After
      two vaccine doses, DEL BAC induced serum neutralizing titers compatible with an
      "expected percentage of protection" above 90%. Plasmid pC DEL stimulated FMDV
      specific humoral responses earlier than DEL BAC, though IgG1 to IgG2 ratios were
      lower than those induced by both DEL BAC and inactivated FMDV-C3 after the second
      dose. DEL BAC induced FMDV-specific secretion of IFN-gamma in peripheral blood
      mononuclear cells of outbred cattle immunized with commercial FMDV vaccine,
      suggesting its capacity to recall anamnestic responses mediated by functional T
      cell epitopes. The results show that exposing FMDV-VP1 major neutralizing
      antigenic site in the context of N-terminal sequences of the VSV G protein can
      overcome the immunological limitations of FMDV-VP1 peptides as effective protein
      and DNA vaccines for cattle.

PMID- 21889543
TI  - The effect of cytokine profiles on the viral response to re-treatment in
      antiviral-experienced patients with chronic hepatitis C virus infection.
AB  - BACKGROUND: There have been few studies on the potential immunological factors
      associated with viral controls in antiviral-experienced patients on a second
      round of combination therapy. In this study, we evaluated the level of systemic
      cytokines and potential impact on combination therapy in both antiviral-naive and
      -experienced patients chronically infected with hepatitis C virus. METHODS:
      Longitudinal analysis of 27 cytokines and chemokines was performed using the
      multiplex Biorad 27 plex assay in 37 antiviral-naive and 24 experienced
      chronically HCV-1b-infected patients during combination therapy with
      peginterferon-alfa and ribavirin. A group of healthy donors was included as the
      control (n=11). RESULTS: Fifty percent of antiviral-experienced chronically HCV
      patients could achieve a delayed and slow virologic response after 48 weeks
      combination therapy, comparing with an early and fast virologic response in
      antiviral-naive patients. A distinction of immune mediators profiling before and
      during antiviral therapy between antiviral-naive and -experienced patients was
      identified, IL-4, IFN-gamma and CCL-3 (MIP-1a) were significantly higher in naive
      patients than those in experienced patients (P=0.005, 0.047 and 0.017,
      respectively) while G-CSF in naive was lower than in experienced patients
      (P<0.05). Notably, higher Th1 type cytokine IFN-gamma and lower Th2 type cytokine
      IL-4 at baseline and week 4 were associated with HCV clearance in naive patients,
      and a similar trend appeared at week 12 in experienced patients. CONCLUSIONS: We
      found a successful second round therapy in antiviral-experienced patients appears
      to be associated with the host immune response. Dominant Th1-polar cytokines,
      especially IFN-gamma, is a potential predictor of viral responsiveness.

PMID- 21889545
TI  - Behavioral alterations and changes in Ca/calmodulin kinase II levels in the
      striatum of connexin36 deficient mice.
AB  - Gap junctions (GJ) are intercellular channels which directly connect the
      cytoplasm of adjacent cells. GJ allow direct cell-to-cell communication via the
      diffusion of ions, metabolites and second messengers such as IP(3). The
      connexin36 (Cx36) protein has been detected in GJ between interneurons of the
      hippocampus, cerebral cortex, striatum, amygdala, the inferior olive, cerebellum
      and other brain structures, such as the olfactory bulb. Cx36 knockout (Cx36 KO)
      mice display changes in synchronous network oscillations in the hippocampus,
      neocortex and inferior olive and exhibit impaired spatial alternation and one
      trial object recognition in a Y-maze. Here, we further characterized the
      behavioral changes induced by Cx36 deficiency in the mouse by using different
      behavioral measures and experimental procedures. Additionally, we examined the
      effects of Cx36 deficiency on acetylcholine esterase (AChE) activity and calcium
      calmodulin kinase II alpha (CaMKII) protein levels in the striatum. The
      homozygous Cx36 KO mice displayed increased locomotion and running speed in the
      open-field, reduced object exploration and impaired one-trial object-place
      recognition. Furthermore, they exhibited more anxiety-like behavior as compared
      to the heterozygous controls in the light-dark box. Homozygous Cx36 KO mice
      exhibited reduced CaMKII levels in the striatum as compared to the heterozygous
      mice. AChE activity in the striatum was not significantly different between
      groups. The present results suggest that Cx36 deficiency in the mouse leads to
      reduced CaMKII levels in the striatum and behavioral changes in open-field
      activity, anxiety-related behavior in the light-dark box and one-trial object
      place recognition.

PMID- 21889544
TI  - Sex differences in the behavioral response to methylphenidate in three adolescent
      rat strains (WKY, SHR, SD).
AB  - Methylphenidate (MPD) is the most widely used drug in the treatment of attention
      deficit hyperactivity disorder (ADHD). ADHD has a high incidence in children and
      can persist in adolescence and adulthood. The relation between sex and the
      effects of acute and chronic MPD treatment was examined using adolescent male and
      female rats from three genetically different strains: spontaneously hyperactive
      rat (SHR), Wistar-Kyoto (WKY) and Sprague-Dawley (SD). Rats from each strain and
      sex were randomly divided into a control group that received saline injections
      and three MPD groups that received either 0.6 or 2.5 or 10mg/kg MPD injections.
      All rats received saline on experimental day 1 (ED1). On ED2 to ED7 and ED11, the
      rats were injected either with saline or MPD and received no treatment on ED8
      ED10. The open field assay was used to assess the dose-response of acute and
      chronic MPD administration. Significant sex differences were found. Female SHR
      and SD rats were significantly more active after MPD injections than their male
      counterparts, while the female WKY rats were less active than the male WKY rats.
      Dose dependent behavioral sensitization or tolerance to MPD treatment was not
      observed for SHR or SD rats, but tolerance to MPD was found in WKY rats for the
      10mg/kg MPD dose. The use of dose-response protocol and evaluating different
      locomotor indices provides the means to identify differences between the sexes
      and the genetic strain in adolescent rats. In addition these differences suggest
      that the differences to MPD treatment between the sexes are not due to the
      reproductive hormones.

PMID- 21889546
TI  - Exogenous oxytocin reverses the decrease of colonic smooth muscle contraction in
      antenatal maternal hypoxia mice via ganglia.
AB  - Oxytocin (OT) has been reported to have a potential protective effect on stress
      induced functional gastrointestinal disorders. This study determined whether
      colonic contraction in adults was affected by antenatal maternal hypoxia, and
      whether OT is involved in antenatal maternal hypoxia induced colonic contraction
      disorder. Isometric spontaneous contractions were recorded in colonic
      longitudinal muscle strips in order to investigate colonic contractions and the
      effects of exogenous OT on the contraction in antenatal maternal hypoxia and
      control mice. Both high potassium and carbachol-induced contractions of proximal
      colon but not distal colon were reduced in antenatal maternal hypoxia mice.
      Exogenous OT decreased the contractions of proximal colonic smooth muscle strips
      in control mice, while it increased contractions in antenatal maternal hypoxia
      mice. OT increased the contractions of distal colonic smooth muscle strips in
      both antenatal maternal hypoxia and control mice. Hexamethonium blocked the OT
      induced potentiation of proximal colon but not distal colon in antenatal maternal
      hypoxia mice. These results suggest that exogenous oxytocin reverses the decrease
      of proximal colonic smooth muscle contraction in antenatal maternal hypoxia mice
      via ganglia.

PMID- 21889547
TI  - Expanding the cellular molecular chaperone network through the ubiquitous
      cochaperones.
AB  - Cellular environments are highly complex and contain a copious variety of
      proteins that must operate in unison to achieve homeostasis. To guide and
      preserve order, multifaceted molecular chaperone networks are present within each
      cell type. To handle the vast client diversity and regulatory demands, a wide
      assortment of chaperones are needed. In addition to the classic heat shock
      proteins, cochaperones with inherent chaperoning abilities (e.g., p23, Hsp40,
      Cdc37, etc.) are likely used to complete a system. In this review, we focus on
      the HSP90-associated cochaperones and provide evidence supporting a model in
      which select cochaperones are used to differentially modulate target proteins,
      contribute to combinatorial client regulation, and increase the overall reach of
      a cellular molecular chaperone network. This article is part of a Special Issue
      entitled: Heat Shock Protein 90 (HSP90).

PMID- 21889548
TI  - Exploration of novel in vitro assays to study drugs against Trichuris spp.
AB  - Though trichuriasis is a significant public health problem, few effective drugs
      are available underscoring the need for new drug therapies. For the evaluation of
      trichuricidal activity of test compounds in vitro an accurate, reliable,
      sensitive, fast and cheap drug sensitivity assay is essential. The aim of the
      present investigation was to evaluate the performance of different in vitro drug
      sensitivity assays in comparison to the standard motility assay. Trichuris muris
      L4 larvae or adult worms were isolated from the intestinal tract from infected
      female C57BL/10 mice and incubated in the presence of ivermectin, levamisole and
      nitazoxanide (200, 100 and 50 MUg/ml) for 72 h. The health status of the worms
      was either evaluated microscopically using a motility scale from 0 to 3 (motility
      assay), by examination of absorbance or emission in response to metabolic
      activity (MTT (Thiazolyl Blue Tetrazolium Bromide) and Alamar Blue assay),
      through analysis of absorbance of an enzyme-substrate reaction (acid phosphatase
      activity assay), by measuring the noise amplitudes (isothermal microcalorimetry
      and xCELLigence System) or the heat flow (isothermal microcalorimetry) of T.
      muris. The Alamar Blue assay, xCELLigence and microcalorimetry compared favorably
      to the standard motility assay. These three assays precisely determined the
      trichuricidal activity of the three test drugs. The acid phosphatase and the MTT
      assays showed a poorer performance than the motility assay. In conclusion, the
      colorimetric Alamar Blue in vitro assay is a good alternative to the motility
      assay to study drug effects against T. muris L4 and adults, since it is easy to
      perform, precise and of low cost.

PMID- 21889549
TI  - Preparation of highly infective Leishmania promastigotes by cultivation on SNB-9
      biphasic medium.
AB  - Protozoan hemoflagellates Leishmania are causative agents of leishmaniases and an
      important biological model for study of host-pathogen interaction. A wide range
      of methods of Leishmania cultivation on both biphasic and liquid media is
      available. Biphasic media are considered to be superior for initial isolation of
      the parasites and obtaining high promastigote infectivity; however, liquid media
      are more suitable for large-scale experiments. The aim of the present study was
      the adaptation and optimization of the cultivation of Leishmania promastigotes on
      a biphasic SNB-9 (saline-neopeptone-blood 9) medium that was originally developed
      for Trypanosoma cultivation and combines the advantages of biphasic and liquid
      media. SNB-9 medium is characterized with a large volume of the liquid phase,
      which facilitates the manipulation with the culture and provides parasite yields
      comparable to parasite yields on such liquid medium as Schneider's Insect Medium.
      We demonstrate that SNB-9 very considerably surpasses Schneider's Insect Medium
      in in vitro infectivity of the parasites. Additionally, we show that the ratio of
      apoptotic parasites, which are important for the infectivity of the inoculum, in
      Leishmania culture in SNB-9 is higher than in Leishmania culture in Schneider's
      Insect Medium. Thus, we demonstrate that the cultivation of Leishmania on SNB-9
      reliably yields highly infective promastigotes suitable for experimental
      infection.

PMID- 21889550
TI  - Intervention of mitochondrial dysfunction-oxidative stress-dependent apoptosis as
      a possible neuroprotective mechanism of alpha-lipoic acid against rotenone
      induced parkinsonism and L-dopa toxicity.
AB  - The current study evidenced hypothesis that mitochondrial dysfunction-oxidative
      stress-dependent apoptotic pathways play a critical role in degeneration of
      dopaminergic neurons in Parkinson's disease. Model of rotenone-induced
      parkinsonism in rats produced decrease in striatal complex I activity and reduced
      glutathione with increase in nitrites concentration and caspase-3 activity. This
      was confirmed by significant correlation of catalepsy score with neurochemical
      parameters. Moreover, electron microscopic examination of striatal neurons
      displayed ultrastructure affection as hyperchromatic nuclei and disrupted
      mitochondria that are typical features of undergoing apoptosis. Administration of
      L-dopa as replacement therapy, although caused symptomatic improvement in
      catalepsy score, but further worsening in neurochemical parameters. Therefore,
      efforts are not only to improve effect of L-dopa, but also to introduce drugs
      provide antiparkinsonian and neuroprotective effects. In this study, alpha-lipoic
      acid exhibited noticeable neuroprotective effects by a mechanism via intervention
      of mitochondrial dysfunction-oxidative stress-dependent apoptotic pathways.
      Combination of alpha-lipoic acid efficiently halting deleterious toxic effects of
      L-dopa, revealed normalization of catalepsy score in addition to amelioration of
      neurochemical parameters and apparent preservation of striatal ultrastructure
      integrity, indicating benefit of both symptomatic and neuroprotective therapy. In
      conclusion, alpha-lipoic acid could be recommended as a disease-modifying therapy
      when given with L-dopa early in course of Parkinson's disease.

PMID- 21889551
TI  - Overexpression and purification of the recombinant diphtheria toxin variant
      CRM197 in Escherichia coli.
AB  - The expression of the recombinant diphtheria toxin mutant CRM197 in bacteria
      other than Corynebacterium diphtheriae has proven to be difficult. Here we
      propose a new and alternative procedure for the production of full-length CRM197
      in Escherichia coli. The present study relates specifically to the expression of
      an artificial sequence and to a method for the isolation and purification of the
      corresponding protein. In particular, a synthetic gene coding for CRM197, bearing
      a short histidine tag and optimized for E. coli codon usage, was cloned in the
      pET9a vector. Accordingly, the over-expression of the protein was simply induced
      with arabinose in E. coli BL21AI. The recombinant protein was insoluble and
      always found inside protein aggregates, which were solubilised using urea.
      Surprisingly, the expression of CRM197, devoid of the short tag, always failed.
      Following a refolding step, the his-tagged CRM197 was purified by affinity and
      gel-filtration chromatography and the purity of the final preparation reached
      95%. Interestingly, the recombinant protein features DNase activity, indicating
      that the presence of the tag is not affecting its biochemical properties.
      However, the removal of the synthetic tag could be easily obtained by incubating
      the target protein with a proper quantity of a commercial enterokinase.

PMID- 21889552
TI  - A novel prokaryotic expression system for biosynthesis of recombinant human
      membrane-bound catechol-O-methyltransferase.
AB  - Membrane proteins constitute 20-30% of all proteins encoded by the genome of
      various organisms. While large amounts of purified proteins are required for
      pharmaceutical and crystallization attempts, there is an unmet need for the
      development of novel heterologous membrane protein overexpression systems.
      Specifically, we tested the application of Brevibacillus choshinensis cells for
      the biosynthesis of human membrane bound catechol-O-methyltransferase (hMBCOMT).
      In terms of the upstream stage moderate to high expression was obtained for
      complex media formulation with a value near 45 nmol/h/mg for hMBCOMT specific
      activity achieved at 20 h culture with 37 degrees C and 250 rpm. Subsequently,
      the efficiency for reconstitution of hMBCOMT is markedly null in the presence of
      ionic detergents, such as sodium dodecyl sulphate (SDS). In general, for non
      ionic and zwiterionic detergents, until a detergent critic micellar concentration
      (CMC) of 1.0 mM, hMBCOMT shows more biological activity at lower detergent
      concentrations while for detergent CMC higher than 1 mM, higher detergent
      concentrations seem to be ideal for hMBCOMT solubilization. Indeed, from the
      detergents tested, the non-ionic digitonin at 0.5% (w/v) appears to be the most
      suitable for hMBCOMT solubilization.

PMID- 21889553
TI  - Association of Vpu with hepatitis C virus NS3/4A stimulates transcription of type
      1 human immunodeficiency virus.
AB  - Type 1 human immunodeficiency virus (HIV-1) and hepatitis C virus (HCV) are
      deadly bloodborne-transmitting pathogens. Due to sharing the routes of
      transmission, co-infection of HIV-1 and HCV is common with a high rate. Co
      infection of HCV affects morbidity and mortality of patients with AIDS and
      impairs their tolerance to antiretroviral therapy. In this study, the roles of
      HCV proteins in the regulation of HIV-1 replication and the molecular mechanism
      involved in such regulation were investigated. We demonstrated that HCV NS3
      protein stimulated HIV-1 LTR transcription and that HIV-1 Vpu protein was
      required for the activation of HIV-1 transcription regulated by HCV NS3/4A
      complex. Further study revealed that Vpu mediated ubiquitination-associated
      degradation of NS4A, detached NS3/4A complex and release NS3 for nuclear
      translocation. Since both degradation of NS4A and activation of HIV-1 LTR were
      closely correlated and mediated by Vpu, we proposed that Vpu impairs the
      stability of NS4A and releases NS3 from NS3/4A complex for the stimulation of HIV
      1 transcription. This study enriched our understanding on HIV-1/HCV co-infection
      and provided new insights in molecular mechanism involved in the co-infection of
      the two viruses.

PMID- 21889554
TI  - Photochemical internalisation of a macromolecular protein toxin using a cell
      penetrating peptide-photosensitiser conjugate.
AB  - Photochemical internalisation (PCI) is a site-specific technique for improving
      cellular delivery of macromolecular drugs. In this study, a cell penetrating
      peptide, containing the core HIV-1 Tat 48-57 sequence, conjugated with a
      porphyrin photosensitiser has been shown to be effective for PCI. Herein we
      report an investigation of the photophysical and photobiological properties of a
      water soluble bioconjugate of the cationic Tat peptide with a hydrophobic
      tetraphenylporphyrin derivative. The cellular uptake and localisation of the
      amphiphilic bioconjugate was examined in the HN5 human head and neck squamous
      cell carcinoma cell line. Efficient cellular uptake and localisation in
      endo/lysosomal vesicles was found using fluorescence detection, and light
      induced, rupture of the vesicles resulting in a more diffuse intracellular
      fluorescence distribution was observed. Conjugation of the Tat sequence with a
      hydrophobic porphyrin thus enables cellular delivery of an amphiphilic
      photosensitiser which can then localise in endo/lysosomal membranes, as required
      for effective PCI treatment. PCI efficacy was tested in combination with a
      protein toxin, saporin, and a significant reduction in cell viability was
      measured versus saporin or photosensitiser treatment alone. This study
      demonstrates that the cell penetrating peptide-photosensitiser bioconjugation
      strategy is a promising and versatile approach for enhancing the therapeutic
      potential of bioactive agents through photochemical internalisation.

PMID- 21889555
TI  - Nanogel with endosome-escaping function.

PMID- 21889556
TI  - Post-translational modifications of pro-opiomelanocrtin related hormones in
      medaka pituitary based on mass spectrometric analyses.
AB  - Direct tissue matrix-assisted laser desorption ionization with time-of-flight
      mass spectrometry analysis provides a selective detection of mass profile for the
      peptides contained into cell secretory granules. By this mass spectrometry with
      slice of pituitary, two novel molecular forms of pro-opimelanocrtin related
      hormone were found in the orange-red strain medaka (Oryzias latipes var.). The
      structures of [N,O-diacetyl Serine(1), O-acetyl Serine(3)]-alpha-melanocyte
      stimulating hormone (MSH) and [hydroxyproline(15)]-beta-MSH, together with
      [phosphoserine(15)]-corticotropin-like intermediate lobe peptide, were determined
      for the first time using a collision-induced dissociation with electrospray
      ionization mass spectrometry. A combination of mass spectrometry analyses is thus
      a powerful tool to lead to the elucidation of the post-translational processing
      from the pre-prohormone.

PMID- 21889558
TI  - Contacts with children and young people and adult risk of suffering herpes
      zoster.
AB  - We carried out a matched case-control study to analyze the possible association
      between exposure to the children and the risk of suffering herpes-zoster in
      adulthood. Cases of herpes zoster in immunocompetent healthy patients aged >= 25
      years seen in the dermatology department of the Sagrado Corazon Hospital in 2007
      2008 were matched with four controls. Data were analyzed using conditional
      logistic regression. 153 cases and 604 matched controls were included. Contacts
      with children were significantly associated with a reduction in the risk of
      suffering herpes zoster in adulthood (adjusted OR 0.56 [0.37-0.85]). Herpes
      zoster vaccination in immunocompetent people aged >= 50 years could counteract
      the possible negative effects of mass varicella vaccination in childhood on the
      epidemiology of herpes zoster in adults.

PMID- 21889557
TI  - Global expression profiling of peripheral Qa-1-restricted
      CD8alphaalpha+TCRalphabeta+ regulatory T cells reveals innate-like features:
      implications for immune-regulatory repertoire.
AB  - Among peripheral regulatory T cells, CD8(+) T cells also play an important role
      in the maintenance of immune homeostasis. A subset of CD8(+) Treg that express
      alphabeta T cell receptor (TCR) and CD8alphaalpha homodimers can recognize TCR
      derived peptides in the context of the class Ib MHC molecule Qa-1. To gain a
      better understanding of the nature and phenotype of CD8alphaalpha(+)TCRalphabeta+
      Treg, a global gene expression profiling using microarray, real-time quantitative
      polymerase chain reaction, and flow-cytometric analysis was performed using
      functional Treg clones and lines. The study findings show that CD8(+) Treg shared
      gene profile expressed by innate-like lymphocytes, including murine
      intraepithelial lymphocytes and thymic CD8alphaalpha(+)TCRalphabeta+ T-cell
      populations. In addition, this subset displays differential expression of several
      key regulatory molecules, including CD200. CD8alphaalpha(+) Treg expressed higher
      levels of a number of natural killer cell-related receptors and molecules
      belonging to the TNF superfamily. Collectively, peripheral class Ib-reactive
      CD8alphaalpha(+)TCRalphabeta+ T cells represent a unique regulatory population
      different from class Ia major histocompatibility complex-restricted conventional
      T cells. These studies have important implications for the regulatory mechanisms
      mediated by the CD8(+) Treg population in general.

PMID- 21889559
TI  - Using the fish plasma model for comparative hazard identification for
      pharmaceuticals in the environment by extrapolation from human therapeutic data.
AB  - Thousands of drugs are currently in use, but only for a few of them experimental
      chronic fish data exist. Therefore, Huggett et al. (Human Ecol Risk Assess 2003;
      9:1789-1799) proposed the fish plasma model (FPM) to extrapolate the potential of
      unintended long-term effects in fish. The FPM compares human therapeutic plasma
      concentrations (HPC(T)) with estimated fish steady-state concentrations
      (FPC(ss)), under the assumption that biological drug targets may be conserved
      across the species. In this study, the influence of using different input
      parameters on the model result was characterised for 42 drugs. The existence of
      structurally and functionally conserved protein targets in zebrafish could not be
      refuted. Thus, the FPM model application was not in contradiction to its basic
      assumption. Further, dissociation of drugs was shown to be important in
      determining the output and model robustness. As the proposed model for FPC(ss)
      estimation was considered to predict accurate values for neutral and lipophilic
      chemicals only, a modified bioconcentration model was used with D(OW) as
      predictor. Using reasonable worst case assumptions, a hazard was indicated for
      one third of the selected drugs. Our results support the notion that this
      approach might help to prioritise among in use drugs to identify compounds where
      follow up evidence should be considered.

PMID- 21889560
TI  - Is switching antidepressants following early nonresponse more beneficial in acute
      phase treatment of depression?: a randomized open-label trial.
AB  - RATIONALE: Treatment guidelines for major depressive disorder (MDD) recommend a
      continuous use of antidepressants for several weeks, while recent meta-analyses
      indicate that antidepressant efficacy starts to appear within 2 weeks and early
      treatment nonresponse is a predictor of subsequent nonresponse. OBJECTIVES: We
      prospectively compared 8-week outcomes between switching antidepressants and
      maintaining the same antidepressant in early nonresponders, to generate a
      hypothesis on possible benefits of early switching strategy. METHOD: Patients
      with MDD without any treatment history for the current episode were included.
      When subjects failed to show an early response (i.e., >=20% improvement in the
      Montgomery-Asberg Depression Rating Scale (MADRS)) to the initial treatment with
      sertraline 50mg at week 2, they were randomly divided into two groups; in the
      Continuing group, sertraline was titrated at 50-100mg, whereas sertraline was
      switched to paroxetine 20-40 mg in the Switching group. A primary outcome measure
      was a response rate (i.e., >=50% improvement in the MADRS) at week 8. RESULTS:
      Among 132 subjects, 41 subjects showed early nonresponse. The Switching group
      (n=20) showed a higher rate of responders than the Continuing group (n=21) (75%
      vs. 19%: p=0.002). Further, the Switching group was also superior in the rate of
      remitters (total score of <=10 in the MADRS) (60% vs. 14%: p=0.004) and
      continuous changes in the MADRS (19.0 vs. 7.5: p<0.001). CONCLUSIONS: Our
      preliminary findings suggest that patients with MDD who fail to show early
      response to an initial antidepressant may derive benefits from the early
      switching antidepressants in the acute-phase treatment of depression.

PMID- 21889561
TI  - Sertraline promotes hippocampus-derived neural stem cells differentiating into
      neurons but not glia and attenuates LPS-induced cellular damage.
AB  - Sertraline is one of the most commonly used antidepressants in clinic. Although
      it is well accepted that sertraline exerts its action through inhibition of the
      reuptake of serotonin at presynaptic site in the brain, its effect on the neural
      stem cells (NSCs) has not been well elucidated. In this study, we utilized NSCs
      separated from the hippocampus of fetal rat to investigate the effect of
      sertraline on the proliferation and differentiation of NSCs. The study
      demonstrated that sertraline had no effect on NSCs proliferation but it
      significantly promoted NSCs to differentiate into serotoninergic neurons other
      than glia cells. Furthermore, we found that sertraline protected NSCs against the
      lipopolysaccharide-induced cellular damage. These data indicate that sertraline
      can promote neurogenesis and protect the viability of neural stem cells.

PMID- 21889563
TI  - Evaluating potential of curcumin loaded solid lipid nanoparticles in aluminium
      induced behavioural, biochemical and histopathological alterations in mice brain.
AB  - Aluminium, a well established neurotoxicant, is reported to be involved in the
      aetiology of Alzheimer's disease (AD) due to its easy admittance and accumulation
      in central nervous system (CNS). Simultaneous curcumin treatment during the
      induction of neurotoxicity by AlCl(3) is reported to provide protection. However,
      the therapeutic potential of curcumin in terms of reversing the neuronal damage
      once induced is limited due to its compromised bioavailability (BA). We prepared
      solid lipid nanoparticles of curcumin (C-SLNs) with enhanced BA (32-155 times)
      and investigated its therapeutic role in alleviating behavioural, biochemical and
      histochemical changes upon oral administration (100mg/kg) of AlCl(3) in male
      Lacca mice. Adverse effects of AlCl(3) were completely reversed by oral
      administration of C-SLNs. Treatment with free curcumin showed <= 15% recovery in
      membrane lipids (LPO) and 22% recovery in acetylcholinesterase (AChE) with
      respect to AlCl(3) treated group. C-SLNs showed significantly better results
      (97.46% and 73% recovery in LPO and AChE) at a dose of 50mg/kg, and the results
      were comparable (p <= 0.001) to those achieved with rivastigmine. Histopathology
      of the brain sections of C-SLNs treated groups also indicated significant
      improvement. Study highlights the potential of C-SLNs for treatment of AD.

PMID- 21889562
TI  - Antidepressant-like effect of Valeriana glechomifolia Meyer (Valerianaceae) in
      mice.
AB  - The antidepressant-like effect of a supercritical CO2 (SCCO2) Valeriana
      glechomifolia extract enriched in valepotriates was investigated in a mice tail
      suspension test (TST) and forced swimming test (FST). The SCCO2 extract decreased
      mice immobility in the FST (0.5-20 mg/kg p.o.) and elicited a biphasic dose
      response relationship in the TST (1-20 mg/kg p.o.) with no alterations in
      locomotor activity and motor coordination (assessed in the open-field and rota
      rod tests, respectively). The anti-immobility effect of the SCCO2 extract (5
      mg/kg, p.o.) was prevented by mice pre-treatment with yohimbine (1 mg/kg, i.p.,
      an alpha2 adrenoceptor antagonist), SCH 23390 (15 MUg/kg, s.c., D1 dopamine
      receptor antagonist) and sulpiride (50 mg/kg, i.p., D2 dopamine receptor
      antagonist). However, mice pre-treatments with prazosin (1 mg/kg, i.p., alpha1
      adrenoceptor antagonist) and p-chlorophenilalanine methyl ester (4*100 mg/kg/day,
      i.p., a serotonin synthesis inhibitor) were not able to block the anti-immobility
      effect of the SCCO2 extract. Administration (p.o.) of the SCCO2 extract (0.25
      mg/kg) and imipramine (10 mg/kg), desipramine (5 mg/kg) and bupropion (3 mg/kg)
      at sub-effective doses significantly reduced mice immobility time in the FST.
      These data provide the first evidence of the antidepressant-like activity of V.
      glechomifolia valepotriates, which is due to an interaction with dopaminergic and
      noradrenergic neurotransmission.

PMID- 21889564
TI  - Fructose and non-fructose sugar intakes in the US population and their
      associations with indicators of metabolic syndrome.
AB  - BACKGROUND: Relationships of sugar intakes with indicators of metabolic syndrome
      are important concerns for public health and safety. For individuals, dietary
      intake data for fructose and other sugars are limited. METHOD: Descriptive
      statistics. The data from 25,506 subjects, aged 12-80 yr, contained in the NHANES
      1999-2006 databases were analyzed for sugar intakes and health parameters.
      RESULTS: Dietary fructose was almost always consumed with other sugars. On
      average, fructose provided 37% of total simple sugar intake and 9% of energy
      intake. In more than 97% of individuals studied, fructose caloric contribution
      was lower than that of non-fructose sugars. Fructose and non-fructose sugar
      intakes had no positive association with blood concentrations of TG, HDL
      cholesterol, glycohemoglobin, uric acid, blood pressure, waist circumference, and
      BMI in the adults studied (aged 19 to 80 yr, n=17,749). CONCLUSION: Daily
      fructose intakes with the American diet averaged approximately 37% of total
      sugars and 9% of daily energy. Fructose was rarely consumed solely or in excess
      over non-fructose sugars. Fructose and non-fructose sugar ordinary consumption
      was not positively associated with indicators of metabolic syndrome, uric acid
      and BMI.

PMID- 21889565
TI  - How porphyrinogenic drugs modeling acute porphyria impair the hormonal status
      that regulates glucose metabolism. Their relevance in the onset of this disease.
AB  - This work deals with the study of how porphyrinogenic drugs modeling acute
      porphyrias interfere with the status of carbohydrate-regulating hormones in
      relation to key glucose enzymes and to porphyria, considering that glucose
      modulates the development of the disease. Female Wistar rats were treated with 2
      allyl-2-isopropylacetamide (AIA) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine
      (DDC) using different doses of AIA (100, 250 and 500mg/kg body weight) and a
      single dose of DDC (50mg DDC/kg body weight). Rats were sacrificed 16h after
      AIA/DDC administration. In the group treated with the highest dose of AIA (group
      H), hepatic 5-aminolevulinic acid synthase (ALA-S) increased more than 300%,
      phosphoenolpyruvate carboxykinase (PEPCK) and glycogen phosphorylase (GP)
      activities were 43% and 46% lower than the controls, respectively, plasmatic
      insulin levels exceeded normal values by 617%, and plasmatic glucocorticoids (GC)
      decreased 20%. GC results are related to a decrease in corticosterone (CORT)
      adrenal production (33%) and a significant reduction in its metabolization by UDP
      glucuronosyltransferase (UGT) (62%). Adrenocorticotropic hormone (ACTH)
      stimulated adrenal production 3-fold and drugs did not alter this process. Thus,
      porphyria-inducing drugs AIA and DDC dramatically altered the status of hormones
      that regulate carbohydrate metabolism increasing insulin levels and reducing GC
      production, metabolization and plasmatic levels. In this acute porphyria model,
      gluconeogenic and glycogenolytic blockages caused by PEPCK and GP depressed
      activities, respectively, would be mainly a consequence of the negative
      regulatory action of insulin on these enzymes. GC could also contribute to PEPCK
      blockage both because they were depressed by the treatment and because they are
      positive effectors on PEPCK. These disturbances in carbohydrates and their
      regulation, through ALA-S de-repression, would enhance the porphyria state
      promoted by the drugs on heme synthesis and destruction. This might be the
      mechanism underlying the "glucose effect" observed in hepatic porphyrias. The
      statistical correlation study performed showed association between all the
      variables studied and reinforce these conclusions.

PMID- 21889566
TI  - Evaluation of Streptococcus mutans biofilms formed on fluoride releasing and non
      fluoride releasing resin composites.
AB  - OBJECTIVES: The aim of this study was to evaluate the acid production, acid
      tolerance and composition of Streptococcus mutans biofilms formed on fluoride
      releasing and non fluoride releasing resin composites. METHODS: S. mutans
      biofilms were formed on saliva-coated discs prepared from fluoride releasing
      (Unifil Flow and F2000) or non fluoride releasing materials (Filtek Z350, GRADIA
      DIRECT and hydroxyapatite). To assess the level of acid production and acid
      tolerance, glycolytic pH drop and proton permeability assays were performed using
      94h old S. mutans biofilms. To evaluate the biofilm composition, the biomass
      (total dry-weight), colony forming unit (CFU), water-insoluble extracellular
      polysaccharides (EPS), water-soluble EPS and intracellular iodophilic
      polysaccharides (IPS) of 94 h old S. mutans biofilms were analysed. The amount of
      fluoride of old culture medium released from the materials during the
      experimental period was also determined. Each assay was performed in duplicate in
      at least four different experiments (n=8). RESULTS: All biofilms showed similar
      initial rates of acid production (0.083-0.089 pH drop/min) and proton
      permeability (0.025-0.036 pH increase/min), irrespective of fluoride release from
      the materials. On the other hand, the amount of biomass, water-insoluble EPS and
      IPS of the biofilms on Unifil Flow, which releases a larger amount of fluoride in
      the early stages of biofilm formation, were significantly lower than those on the
      other materials (up to 27%, 38% and 36% reduction in biomass, water-insoluble and
      IPS, respectively). CONCLUSIONS: Our finding suggests that fluoride releasing
      resin composites might contribute to the decrease in cariogenic composition of S.
      mutans biofilms if an appropriate amount of fluoride is released in the early
      stages of biofilm formation.

PMID- 21889567
TI  - Pharmacological and structural characterization of long-sarafotoxins, a new
      family of endothelin-like peptides: Role of the C-terminus extension.
AB  - Long-sarafotoxins (l-SRTXs) have recently been identified in both the venom of
      Atractaspis microlepidota and that of Atractaspis irregularis. They are
      characterized by different C-terminus extensions that follow the invariant Trp21,
      which plays a crucial role in endothelin-receptor binding. We initially
      determined the toxicity and three-dimensional structures of two chemically
      synthesized l-SRTXs that have different C-terminus extensions, namely SRTX-m (24
      aa, including extension "D-E-P") and SRTX-i3 (25 aa, including extension "V-N-R
      N"). Both peptides were shown to be highly toxic in mice and displayed the
      cysteine-stabilized alpha-helical motif that characterizes endothelins and short
      SRTXs, to which a longer C-terminus with variable flexibility is added. To
      discern the functional and pharmacological consequences of the supplementary
      amino acids, different chimerical as well as truncated forms of SRTX were
      designed and synthesized. Thus, we either removed the extra-C-terminal residues
      of SRTX-m or i3, or grafted the latter onto the C-terminal extremity of a short
      SRTX (s-SRTX) (ie. SRTX-b). Our competitive binding assays where SRTXs competed
      for iodinated endothelin-1 binding to cloned ET(A) and ET(B) receptor subtypes
      over-expressed in CHO cells, revealed the essential role of the C-terminus
      extensions for ET-receptor recognition. Indeed, l-SRTXs displayed an affinity
      three to four orders of magnitude lower as compared to SRTX-b for the two
      receptor subtypes. Moreover, grafting the C-terminus extension to SRTX-b induced
      a drastic decrease in affinity, while its removal (truncated l-SRTXs) yielded an
      affinity for ET-receptors similar to that of s-SRTXs. Furthermore, we established
      by intracellular Ca(2+) measurements that l-SRTXs, as well as s-SRTXs, display
      agonistic activities. We thus confirmed in these functional assays the major
      difference in potency for these two SRTX families as well as the crucial role of
      the C-terminus extension in their various pharmacological profiles. Finally, one
      of the chimeric toxin synthesized in this study appears to be one of the most
      potent and selective ligand of the ET(B) receptor known to date.

PMID- 21889568
TI  - Motifs in the C-terminal region of the Penicillium chrysogenum ACV synthetase are
      essential for valine epimerization and processivity of tripeptide formation.
AB  - The first step in the penicillin biosynthetic pathway is the non-ribosomal
      condensation of L-alpha-aminoadipic acid, L-cysteine and L-valine into the
      tripeptide delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV). This reaction
      is catalysed by the multienzyme ACV synthetase (ACVS), which is encoded in the
      filamentous fungus Penicillium chrysogenum by the pcbAB gene. This enzyme
      contains at least ten catalytic domains. The precise role of the C-terminal
      domain of this multidomain NRPS still remains obscure. The C-terminal region of
      ACVS bears the epimerase and the thioesterase domains and may be involved in the
      epimerization of LLL-ACV to LLD-ACV and in the hydrolysis of the thioester bond.
      In this work, the conserved motifs (3371)EGHGRE(3376) (located in the putative
      epimerase domain) and (3629)GWSFG(3633) (located in the thioesterase domain) were
      changed by site-directed-mutagenesis to LGFGLL and GWAFG, respectively. In
      addition, the whole thioesterase domain (230 amino acids) and the different parts
      of this domain were deleted. The activity of these mutant enzymes was assessed in
      vivo by two different procedures: i) through the quantification of bisACV
      produced by the fungus and ii) by quantifying the benzylpenicillin production
      using tailored strains of P. chrysogenum, which lack the pcbAB gene, as host
      strains. All indicated mutant enzymes showed lower or null activity than the
      control strain confirming that E3371, H3373, R3375 and E3376 belong to the
      epimerase active centre. Different fragments included in the C-terminal region of
      ACVS control thioester hydrolysis. Overexpression of the sequence encoding the
      ACVS integrated thioesterase domain as a separate (stand-alone) transcriptional
      unit complemented mutants lacking the integrated thioesterase domain, although
      with low ACV releasing activity, suggesting that the stand-alone thioesterease
      interacts with the other ACVS domains.

PMID- 21889569
TI  - Frontal late positivity in dental phobia: a study on gender differences.
AB  - Although dental phobia afflicts men and women, gender differences in neural
      correlates of this disorder have not been investigated thus far. We recorded
      event-related potential (ERPs) in 30 individuals with dental phobia (15 women, 15
      men with comparable disorder severity) and 30 nonphobic controls (15 women, 15
      men) while they passively viewed pictures depicting dental treatment, generally
      fear-eliciting, disgust-eliciting and neutral contents. Male and female
      individuals with dental phobia as compared with controls displayed an enlarged
      centro-parietal late positivity (300-1500 ms). Gender difference concerned
      prefrontal ERPs. Only men with dentophobia showed an enhanced positivity towards
      the phobic relative to the neutral pictures in the time window between 300 and
      1500 ms. Such a differentiation was absent in the other groups (male controls,
      female phobics, female controls). This finding indicates a gender-dependent
      recruitment of frontal attention networks in dental phobia and might reflect that
      male and female sufferers of dentophobia differ with regard to controlled
      attention focusing and cognitive avoidance during exposure.

PMID- 21889570
TI  - Effort-reward imbalance, overcommitment, and cellular immune measures among white
      collar employees.
AB  - We investigated whether chronic job stress, i.e., effort-reward imbalance (ERI)
      and overcommitment is associated with cellular immunity among 190 male and 157
      female white-collar daytime employees (mean age 38; range 22-69 years).
      Participants provided a blood sample for the measurement of circulating immune
      (natural killer (NK), B, and T) cell counts and NK cell cytotoxicity (NKCC) and
      completed a questionnaire survey during April to June 2002. Stepwise multiple
      linear regression analyses revealed that NK cells were associated with effort
      (beta=-.230; p=.013), reward (beta=.169; p=.047), and ERI (beta=-.182; p=.047)
      scores but not with overcommitment in men; reward score was positively associated
      with NKCC (beta=.167; p=.049) and inversely associated with B cells (beta=-.181;
      p=.030). No significant associations were found in women. Although the picture
      remains less clear in women, our findings suggest a potential immunological
      pathway linking adverse working conditions and stress-related disorders in men.

PMID- 21889571
TI  - Vitamin D and diabetes: its importance for beta cell and immune function.
AB  - Experimental evidence indicates that vitamin D may play a role in the defense
      against type 1 diabetes (T1D) as well as type 2 diabetes (T2D). Epidemiological
      data have established a link between vitamin D deficiency and an increased
      incidence of both T1D and T2D, whereas early and long-term vitamin D
      supplementation may decrease the risk of these disorders. The protective effects
      of vitamin D are mediated through the regulation of several components such as
      the immune system and calcium homeostasis. However, an increasing amount of
      evidence suggests that vitamin D also affects beta cells directly thereby
      rendering them more resistant to the types of cellular stress encountered during
      T1D and T2D. This review evaluates the role of vitamin D signaling in the
      pathogenesis of T1D and T2D with a special emphasis on the direct effects of
      vitamin D on pancreatic beta cells.

PMID- 21889572
TI  - Melatonin: the smart killer: the human trophoblast as a model.
AB  - Melatonin has both the ability to induce intrinsic apoptosis in tumor cells while
      it inhibits it in non-tumor cells. Melatonin kills tumor cells through induction
      of reactive oxygen species generation and activation of pro-apoptotic pathways.
      In contrast, melatonin promotes the survival of non-tumor cells due to its
      antioxidant properties and the inhibition of pro-apoptotic pathways. In primary
      human villous trophoblast, a known pseudo-tumorigenic tissue, melatonin promotes
      the survival through inhibition of the Bax/Bcl-2 pathway while in BeWo
      choriocarcinoma cell line melatonin induces permeabilization of the mitochondrial
      membrane leading to cellular death. These findings suggest that the trophoblast
      is a good model to study the differential effects of melatonin on the intrinsic
      apoptosis pathway. This review describes the differential effects of melatonin on
      the intrinsic apoptosis pathway in tumor and non-tumor cells and presents the
      trophoblast as a novel model system in which to study these effects of melatonin.

PMID- 21889573
TI  - Intracellular Ca(2+) channels - a growing community.
AB  - The Ca(2+) signals that control almost every cellular activity are generated by
      regulating Ca(2+) transport, usually via Ca(2+)-permeable channels, across the
      plasma membrane or the membranes of intracellular organelles. The most widespread
      and best understood of the intracellular Ca(2+) channels are inositol
      trisphosphate receptors (IP(3)R) and ryanodine receptors, most of which are
      expressed in the endoplasmic or sarcoplasmic reticulum. However, accumulating
      evidence suggests physiological roles for many additional Ca(2+) channels in both
      ER and other intracellular organelles. Interactions between these channels,
      whether mediated by Ca(2+) itself or interactions between proteins, is a
      recurrent feature of the Ca(2+) signals evoked by physiological stimuli. We focus
      on two specific examples, clustering of IP(3)Rs and NAADP (nicotinic acid
      dinucleotide phosphate)-evoked Ca(2+) release from endo-lysosomes, to illustrate
      the diversity of Ca(2+) channels and the interplay between them.

PMID- 21889574
TI  - Association analysis between the Val66Met polymorphism in the brain-derived
      neurotrophic factor (BDNF) gene and treatment response to venlafaxine XR in
      generalized anxiety disorder.
AB  - While antidepressant drugs are used to treat generalized anxiety disorder (GAD),
      patients vary greatly in their treatment response. Evidence shows genetic factors
      may play a role in treatment response in GAD. We examined whether the BDNF gene,
      which has been shown to play a role in antidepressant treatment response in major
      depressive disorder (MDD), also has an effect in GAD. In our study, 155 patients
      diagnosed with GAD received venlafaxine XR treatment as part of an 18-month
      relapse prevention study. Genotypes were obtained for the BDNF functional variant
      rs6265 (Val66Met) for the entire sample (n=155); however, only the European
      American (EA) population was considered (n=111) for pharmacogenetic analysis. We
      did not find a significant association between rs6265 and antidepressant
      treatment response in our GAD population. Future studies in larger populations
      will need to be conducted to further elucidate the pharmacogenetic role of this
      variant in anxiety disorders.

PMID- 21889575
TI  - Rosiglitazone enhances the proliferation of neural progenitor cells and inhibits
      inflammation response after spinal cord injury.
AB  - It has been previously shown that peroxisome proliferators-activated receptor
      gamma (PPAR-gamma) is beneficial for nervous system injury. In present study, we
      examined the effect of rosiglitazone, a PPAR-gamma agonist, on spinal cord injury
      (SCI) in rats. SCI was induced by dropping a 10g weight rod at a height of 25mm.
      The animals were randomly divided into vehicle group, rosiglitazone treated
      group, and G3335 treated group. Locomotor function recovery was evaluated by the
      Basso-Beattie-Bresnahan locomotor rating scale (BBB scale), NF-kappaB expression
      and endogenous neural progenitor cells (NPCs) proliferation and differentiation
      was assessed by flow cytometry and immunohistochemistry. Compared with the
      vehicle groups, we found that the rosiglitazone could significantly ameliorate
      locomotor recovery, reduce NF-kappaB expression, and increase the proliferation
      of endogenous NPCs. when the PPAR-gamma antagonist was use, these effects were
      abolished. However, neurons differentiating from endogenous NPCs were inhibited
      when PPAR-gamma was activated. Our results suggest that the activation of PPAR
      gamma may be a potential alternative treatment for spinal cord injury.

PMID- 21889576
TI  - Contributions of vision and proprioception to arm movement planning in the
      vertical plane.
AB  - The roles of visual and somatosensory information in arm movement planning remain
      enigmatic. Previous studies have examined these roles by dissociating visual and
      somatosensory cues about limb position prior to movement onset and examining the
      resulting effects on movements performed in the horizontal plane. Here we
      examined the effects of misaligned limb position cues prior to movement onset as
      reaches were planned and executed along different directions in the vertical
      plane. Movements were planned with somatosensory and visual feedback aligned at
      the starting position of the reach or with visual feedback displaced horizontally
      (Experiment 1) or vertically (Experiment 2). As in the horizontal plane, changes
      in movement directions induced by misaligned feedback indicated that vision and
      proprioception were both generally taken into account when planning vertical
      plane movements. However, we also found evidence that the contributions of vision
      and proprioception differed across target directions and between directions of
      displaced visual feedback. These findings suggest that the contributions of
      vision and proprioception to movement planning in the vertical plane reflect the
      unique multisensory and biomechanical demands associated with moving against
      gravity.

PMID- 21889577
TI  - Effects of D-cycloserine on extinction and reinstatement of morphine-induced
      conditioned place preference.
AB  - d-Cycloserine (DCS), a partial agonist at the strychnine-insensitive glycine
      recognition site on the N-methyl-d-aspartate (NMDA) receptor complex, has been
      shown to facilitate the extinction and prevent the relapse of cocaine-induced
      conditioned place preference (CPP) when administered before or after each
      extinction trail. However, some studies have suggested that DCS does not
      influence or even enhance relapse of seeking behavior on cocaine self
      administration (SA) in rats or cocaine-dependent individuals undergoing clinical
      exposure treatment. Furthermore, there are no reports on the effects of DCS and
      the extinction of morphine-conditioned behaviors in mice. The present study
      investigated the effects of DCS on extinction by exposing mice to drug-paired
      cues and the subsequent reinstatement of morphine-primed CPP. Our results showed
      that DCS at doses of 7.5, 15, and 30mg/kg did not induce conditioned appetitive
      or aversive effects and DCS combined with morphine conditioning failed to affect
      the acquisition of morphine-induced CPP. Moreover, pretreatment with DCS (7.5,
      15, and 30mg/kg, i.p.) prior to extinction training had no significant effects on
      the extinction and subsequent morphine-primed reinstatement of morphine-induced
      CPP. These results suggested that DCS may not be a powerful adjunct for cue
      exposure therapy of opioid addiction. In view of differing outcomes in both
      preclinical and clinical studies, the potential of DCS in exposure treatment of
      drug-seeking behaviors should be carefully evaluated.

PMID- 21889578
TI  - Sex differences in a landmark environmental re-orientation task only during the
      learning phase.
AB  - Sex differences are consistently reported in human navigation. Indeed, to orient
      themselves during navigation women are more likely to use landmark-based
      strategies and men Euclidean-based strategies. The difference could be due to
      selective social pressure, which fosters greater spatial ability in men, or
      biological factors. And the great variability of the results reported in the
      literature could be due to the experimental setting more than real differences in
      ability. In this study, navigational behaviour was assessed by means of a place
      learning task in which a modified version of the Morris water maze for humans was
      used to evaluate sex differences. In using landmarks, sex differences emerged
      only during the learning phase. Although the men were faster than the women in
      locating the target position, the differences between the sexes disappeared in
      delayed recall.

PMID- 21889579
TI  - Motor lateralization is characterized by a serial hybrid control scheme.
AB  - Our previous studies of limb coordination in healthy right- and left-handers led
      to the development of a theoretical model of motor lateralization, dynamic
      dominance, which was recently supported by studies in patients with unilateral
      stroke. One of our most robust findings was on single-joint movements in young
      healthy subjects [Sainburg and Schaefer (2004) J Neurophysiol 92:1374-1383]. In
      this study, subjects made elbow joint reaching movements toward four targets of
      different amplitudes with each arm. Although both arms achieved equivalent task
      performance, each did so through different strategies. The dominant arm strategy
      scaled peak acceleration with peak velocity and movement extent, while the
      nondominant strategy adjusted acceleration duration to achieve the different
      velocities and distances. We now propose that these observed interlimb
      differences can be explained using a serial hybrid controller in which movements
      are initiated using predictive control and terminated using impedance control.
      Further, we propose that the two arms should differ in the relative time that
      control switches from the predictive to the impedance mechanisms. We present a
      mathematical formulation of our hybrid controller and then test the plausibility
      of this control paradigm by investigating how well our model can explain
      interlimb differences in experimental data. Our findings confirm that the model
      predicts early shifts between controllers for left arm movements, which rely on
      impedance control mechanisms, and late shifts for right arm movements, which rely
      on predictive control mechanisms. This is the first computational model of motor
      lateralization and is consistent with our theoretical model that emerged from
      empirical findings. It represents a first step in consolidating our theoretical
      understanding of motor lateralization into an operational model of control.

PMID- 21889580
TI  - Chemical stimulation of the ST36 acupoint reduces both formalin-induced
      nociceptive behaviors and spinal astrocyte activation via spinal alpha-2
      adrenoceptors.
AB  - Spinal astrocytes have emerged as important mechanistic contributors to
      pathological and chronic pain. Recently, we have demonstrated that injection of
      diluted bee venom (DBV) into the Zusanli (ST36) acupoint produces a potent anti
      nociceptive effect via the activation of spinal alpha-2 adrenoceptors. However,
      it is unclear if this anti-nociceptive effect is associated with alterations in
      spinal astrocytes. Thus, the present study was designed to determine: (1) whether
      DBV's anti-nociceptive effect in the formalin test involves suppression of spinal
      astrocyte activation; (2) whether DBV-induced astrocyte inhibition is mediated by
      spinal alpha-2 adrenoceptors; and (3) whether this glial modulation is
      potentiated by intrathecal administration of the glial metabolic inhibitor,
      fluorocitrate (FC) in combination with DBV injection. DBV was injected directly
      into the ST36 acupoint, and spinal expression of the astrocytic marker, glial
      fibrillary acidic protein (GFAP), was assessed together with effects on formalin
      induced nociception. DBV treatment reduced pain responses in the late phase of
      the formalin test and significantly blocked the formalin-evoked increase in
      spinal GFAP expression. These effects of DBV were prevented by intrathecal
      pretreatment with selective alpha-2A and alpha-2C adrenoceptor antagonists.
      Moreover, low dose intrathecal injection of FC in conjunction with low dose DBV
      injection into the ST36 acupoint synergistically suppressed pain responses and
      GFAP expression. These results demonstrate that DBV stimulation of the ST36
      acupoint inhibits the formalin-induced activation of spinal astrocytes and
      nociceptive behaviors in this inflammatory pain model and this inhibition is
      associated with the activation of spinal alpha-2 adrenoceptors.

PMID- 21889581
TI  - Metabolomic analysis of the toxic effects of chronic exposure to low-level
      dichlorvos on rats using ultra-performance liquid chromatography-mass
      spectrometry.
AB  - The purpose of the current study was to assess the effects of long-term exposure
      to low levels of DDVP on the biochemical parameters and metabolic profiles of
      rats. Three different doses (2.4, 7.2, and 21.6 mg/kg body weight/day) of DDVP
      were administered to rats through their drinking water over 24 weeks. Significant
      changes in blood cholinesterase, creatinine, urea nitrogen, aspartate
      aminotransferase, alanine aminotransferase, and albumin concentrations were
      observed in the middle and high dose groups. Changes in the concentration of some
      urine metabolites were detected via ultra performance liquid chromatography-mass
      spectrometry (UPLC-MS). Dimethyl phosphate (DMP), which was exclusively detected
      in the treated groups, can be an early, sensitive biomarker for DDVP exposure.
      Moreover, DDVP treatment resulted in an increase in the lactobionic acid, estrone
      sulfate, and indoxyl sulfic concentrations, and a decrease in citric acid,
      suberic acid, gulonic acid, urea, creatinine, and uric acid. These results
      suggest that chronic exposure to low-level DDVP can cause a disturbance in
      carbohydrate and fatty acid metabolism, the antioxidant system, etc. Therefore,
      an analysis of the metabolic profiles can contribute to the understanding of the
      adverse effects of long-term exposure to low doses of DDVP.

PMID- 21889582
TI  - Nanosuspensions as advanced printing ink for accurate dosing of poorly soluble
      drugs in personalized medicines.
AB  - Folic acid was used as a model drug to demonstrate the advantages of formulating
      poorly soluble drugs as nanosuspensions and their use in an inkjet-type printing
      technique to produce personalized medicines. 10% folic acid nanosuspensions
      stabilized with Tween 20, a stabilizer showing the best wetting potential for
      folic acid, were prepared via high pressure homogenization. The particle size of
      the folic acid nanosuspension was well below 5 MUm being a prerequisite for
      inkjet type printing technique. A good reproducibility of the particle size of
      folic acid nanosuspension prepared via high pressure homogenization was found. As
      indicated by the zeta potential the formulation showed a good storage stability.
      High pressure homogenization had no influence on the crystalline state of folic
      acid. An increase in the saturation solubility by 53.7% was found reducing the
      particle size from the micrometer range to the nanometer range. The dissolution
      velocity of the folic acid nanosuspension was significantly enhanced compared to
      a folic acid suspension, i.e. after 5 min 78.6% of the folic acid was dissolved
      from the nanosuspension and only 6.2% from the suspension. Moreover, the printing
      of 10% folic acid nanosuspension could be successfully demonstrated.

PMID- 21889583
TI  - Validation of USP apparatus 4 method for microsphere in vitro release testing
      using Risperdal Consta.
AB  - The current manuscript addresses the need for a validated in vitro release
      testing method for controlled release parenteral microspheres. A USP apparatus 4
      method was validated with the objective of possible compendial adaptation for
      microsphere in vitro release testing. Commercial microspheres (Risperdal Consta)
      were used for method validation. Accelerated and real-time release tests were
      conducted. The accelerated method had significantly reduced test duration and
      showed a good correlation with the real-time release profile (with limited number
      of sample analysis). Accelerated conditions were used for method validation
      (robustness and reproducibility). The robustness testing results revealed that
      release from the microspheres was not flow rate dependent and was not affected by
      minor variations in the method (such as cell preparation technique, amount of
      microspheres, flow-through cell size and size of glass beads). The significant
      difference in the release profile with small variations (+/- 0.5 degrees C) in
      temperature was shown to be due to a change in risperidone catalyzed PLGA
      degradation in response to temperature. The accelerated method was reproducible
      as changing the system/equipment or the analyst did not affect the release
      profile. This work establishes the suitability of the modified USP apparatus 4
      for possible compendial adaptation for drug release testing of microspheres.

PMID- 21889584
TI  - Nuclear delivery of a therapeutic peptide by long circulating pH-sensitive
      liposomes: benefits over classical vesicles.
AB  - The purpose of this study is to propose a suitable vector combining increased
      circulation lifetime and intracellular delivery capacities for a therapeutic
      peptide. Long circulating classical liposomes [SPC:CHOL:PEG-750-DSPE (47:47:6
      molar% ratio)] or pH-sensitive stealth liposomes [DOPE:CHEMS:CHOL:PEG(750)-DSPE
      (43:21:30:6 molar% ratio)] were used to deliver a therapeutic peptide to its
      nuclear site of action. The benefit of using stealth pH-sensitive liposomes was
      investigated and formulations were compared to classical liposomes in terms of
      size, shape, charge, encapsulation efficiency, stability and, most importantly,
      in terms of cellular uptake. Confocal microscopy and flow cytometry were used to
      evaluate the intracellular fate of liposomes themselves and of their hydrophilic
      encapsulated material. Cellular uptake of peptide-loaded liposomes was also
      investigated in three cell lines: Hs578t human epithelial cells from breast
      carcinoma, MDA-MB-231 human breast carcinoma cells and WI-26 human diploid lung
      fibroblast cells. The difference between formulations in terms of peptide
      delivery from the endosome to the cytoplasm and even to the nucleus was
      investigated as a function of time. Characterization studies showed that both
      formulations possess acceptable size, shape and encapsulation efficiency but
      cellular uptake studies showed the important benefit of the pH-sensitive
      formulation over the classical one, in spite of liposome PEGylation. Indeed,
      stealth pH-sensitive liposomes were able to deliver hydrophilic materials
      strongly to the cytoplasm. Most importantly, when encapsulated in pH-sensitive
      stealth liposomes, the peptide was able to reach the nucleus of tumorigenic and
      non tumorigenic breast cancer cells.

PMID- 21889585
TI  - Engineering of microorganisms for the production of biofuels and perspectives
      based on systems metabolic engineering approaches.
AB  - The increasing oil price and environmental concerns caused by the use of fossil
      fuel have renewed our interest in utilizing biomass as a sustainable resource for
      the production of biofuel. It is however essential to develop high performance
      microbes that are capable of producing biofuels with very high efficiency in
      order to compete with the fossil fuel. Recently, the strategies for developing
      microbial strains by systems metabolic engineering, which can be considered as
      metabolic engineering integrated with systems biology and synthetic biology, have
      been developed. Systems metabolic engineering allows successful development of
      microbes that are capable of producing several different biofuels including
      bioethanol, biobutanol, alkane, and biodiesel, and even hydrogen. In this review,
      the approaches employed to develop efficient biofuel producers by metabolic
      engineering and systems metabolic engineering approaches are reviewed with
      relevant example cases. It is expected that systems metabolic engineering will be
      employed as an essential strategy for the development of microbial strains for
      industrial applications.

PMID- 21889586
TI  - Peripheral bacterial endotoxin administration triggers both memory consolidation
      and reconsolidation deficits in mice.
AB  - Peripherally administered inflammatory stimuli, such as lipopolysaccharide (LPS),
      induce the synthesis and release of proinflammatory cytokines and chemokines in
      the periphery and the central nervous system, and trigger a variety of
      neurobiological responses. Indeed, prior reports indicate that peripheral LPS
      administration in rats disrupts contextual fear memory consolidation processes,
      potentially due to elevated cytokine expression. We used a similar, but partially
      olfaction-based, contextual fear conditioning paradigm to examine the effects of
      LPS on memory consolidation and reconsolidation in mice. Additionally,
      interleukin-1beta (IL-1beta), brain-derived neurotrophic factor (BDNF), and zinc
      finger (Zif)-268 mRNA expression in the hippocampus and the cortex, along with
      peripheral cytokines and chemokines, were assessed. As hypothesized, LPS
      administered immediately or 2 h, but not 12 h, post-training impaired memory
      consolidation processes that support the storage of the conditioned contextual
      fear memory. Additionally, as hypothesized, LPS administered immediately
      following the fear memory trace reactivation session impaired memory
      reconsolidation processes. Four hours post-injection, both central cytokine and
      peripheral cytokine and chemokine levels were heightened in LPS-treated animals,
      with a simultaneous decrease in BDNF, but not Zif-268, mRNA. Collectively, these
      data reinforce prior work showing LPS- and cytokine-related effects on memory
      consolidation, and extend this work to memory reconsolidation.

PMID- 21889587
TI  - Comparative pharmacokinetics of perfluorooctanesulfonate (PFOS) in rats, mice,
      and monkeys.
AB  - Perfluorooctanesulfonate (PFOS) has been found in biological samples in wildlife
      and humans. The geometric mean half-life of serum elimination of PFOS in humans
      has been estimated to be 4.8 years (95% CI, 4.0-5.8). A series of studies was
      undertaken to establish pharmacokinetic parameters for PFOS in rats, mice, and
      monkeys after single oral and/or IV administration of K(+)PFOS. Animals were
      followed for up to 23 weeks, and pharmacokinetic parameters were determined by
      WinNonlin(r) software. Rats and mice appeared to be more effective at eliminating
      PFOS than monkeys. The serum elimination half-lives in the rodent species were on
      the order of 1-2 months; whereas, in monkeys, the serum elimination half lives
      approximated 4 months. Collectively, these studies provide valuable insight for
      human health risk assessment regarding the potential for accumulation of body
      burden in humans on repeated exposure to PFOS and PFOS-generating materials.

PMID- 21889588
TI  - In utero and lactational exposure to fenvalerate disrupts reproductive function
      in female rats.
AB  - Fenvalerate is a synthetic pyrethroid insecticide used in agriculture and
      domestic insect control. Some studies have proposed that it may act as an
      environmental estrogen; other studies suggest possible genotoxicity in germ
      cells. This study aimed to evaluate the effects of fenvalerate on the female
      reproduction in rats whose mothers were exposed during gestation and lactation.
      Pregnant Wistar rats were exposed to fenvalerate (40 mg/kg) or corn oil (vehicle)
      orally from gestational day 12 until the end of lactation. The dose selection was
      based on previous studies, whereas this was considered an effective dose. Results
      showed decreases in ovarian weight, pre-antral follicles and corpora lutea at PND
      75 and an increase in the resorption number, when fertility test was performed at
      PND 80. Under some experimental conditions, fenvalerate may impair reproductive
      development of female offspring, manifested as reduced fecundity and ovulation
      number, resulting from the impairment in corpora lutea counting.

PMID- 21889589
TI  - A lymphoblast model for IDH2 gain-of-function activity in d-2-hydroxyglutaric
      aciduria type II: novel avenues for biochemical and therapeutic studies.
AB  - The recent discovery of heterozygous isocitrate dehydrogenase 2 (IDH2) mutations
      of residue Arg(140) to Gln(140) or Gly(140) (IDH2(wt/R140Q), IDH2(wt/R140G)) in d
      2-hydroxyglutaric aciduria (D-2-HGA) has defined the primary genetic lesion in
      50% of D-2-HGA patients, denoted type II. Overexpression studies with IDH1(R132H)
      and IDH2(R172K) mutations demonstrated that the enzymes acquired a new function,
      converting 2-ketoglutarate (2-KG) to d-2-hydroxyglutarate (D-2-HG), in lieu of
      the normal IDH reaction which reversibly converts isocitrate to 2-KG. To confirm
      the IDH2(wt/R140Q) gain-of-function in D-2-HGA type II, and to evaluate potential
      therapeutic strategies, we developed a specific and sensitive IDH2(wt/R140Q)
      enzyme assay in lymphoblasts. This assay determines gain-of-function activity
      which converts 2-KG to D-2-HG in homogenates of D-2-HGA type II lymphoblasts, and
      uses stable-isotope-labeled 2-keto[3,3,4,4-(2)H(4)]glutarate. The specificity and
      sensitivity of the assay are enhanced with chiral separation and detection of
      stable-isotope-labeled D-2-HG by ultra performance liquid chromatography-tandem
      mass spectrometry (UPLC-MS/MS). Eleven potential inhibitors of IDH2(wt/R140Q)
      enzyme activity were evaluated with this procedure. The mean reaction rate in D-2
      HGA type II lymphoblasts was 8-fold higher than that of controls and D-2-HGA type
      I cells (14.4nmolh(-1)mgprotein(-1) vs. 1.9), with a corresponding 140-fold
      increase in intracellular D-2-HG level. Optimal inhibition of IDH2(wt/R140Q)
      activity was obtained with oxaloacetate, which competitively inhibited
      IDH2(wt/R140Q) activity. Lymphoblast IDH2(wt/R140Q) showed long-term cell culture
      stability without loss of the heterozygous IDH2(wt/R140Q) mutation, underscoring
      the utility of the lymphoblast model for future biochemical and therapeutic
      studies.

PMID- 21889591
TI  - Gene therapy for amyotrophic lateral sclerosis.
AB  - Gene therapy continues to be a potential option for amyotrophic lateral sclerosis
      (ALS). This chapter will inform the reader about promising therapeutic transgenes
      and proof-of-principle studies in transgenic rodent models of ALS. Challenges
      regarding the disease targets and time for therapeutic intervention will be also
      discussed. Finally, restorative therapy for ALS, as well as gene therapy for
      other motor neuron diseases will be briefly reviewed.

PMID- 21889592
TI  - Network excitability in a model of chronic temporal lobe epilepsy critically
      depends on SK channel-mediated AHP currents.
AB  - Hippocampal CA1 pyramidal neurons generate an after-hyperpolarization (AHP) whose
      medium component is thought to be generated by small-conductance Ca(2+)-activated
      K(+) channels (SK channels). Neuronal excitability is increased in epilepsy, and
      the AHP in turn is fundamentally involved in regulation of cellular excitability.
      We therefore investigated the involvement of the SK channel-mediated AHP in
      controlling cell and network excitability in the pilocarpine model epilepsy. Both
      acutely isolated CA1 pyramidal cells and isolated hippocampal slices were
      investigated in terms of the impact of SK channel-mediated AHP on
      hyperexcitability. Our findings show that pilocarpine-treated chronically
      epileptic rats exhibit significantly reduced SK channel-mediated hyperpolarizing
      outward current which was accompanied by a significant decrease in the somatic
      AHP. Paradoxically, inhibiting SK channels strongly exacerbated 0-Mg(2+)-induced
      epileptiform activity in slices from pilocarpine-treated animals, while having a
      significantly smaller effect in control tissue. This suggests that in chronically
      epileptic tissue, network excitability very critically depends on the remaining
      SK-channel mediated AHP. Additional real-time RT-PCR and semiquantitative Western
      blot experiments revealed that both the SK2 channel transcript and protein were
      significantly downregulated in the epileptic CA1 region. We conclude that SK2
      channels are down-regulated in chronic epilepsy underlying the impaired SK
      channel function in CA1 pyramidal cells, and a further reduction of the remaining
      critical mass of SK channels results in an acute network decompensation.

PMID- 21889590
TI  - Volume of white matter hyperintensities in healthy adults: contribution of age,
      vascular risk factors, and inflammation-related genetic variants.
AB  - Aging is associated with appearance of white matter hyperintensities (WMH) on MRI
      scans. Vascular risk and inflammation, which increase with age, may contribute to
      white matter deterioration and proliferation of WMH. We investigated whether
      circulating biomarkers and genetic variants associated with elevated vascular
      risk and inflammation are associated with WMH volume in healthy adults (144
      volunteers, 44-77 years of age). We examined association of WMH volume with age,
      sex, hypertension, circulating levels of total plasma homocysteine (tHcy),
      cholesterol (low-density lipoprotein), and C-reactive protein (CRP), and four
      polymorphisms related to vascular risk and inflammation: Apolipoprotein epsilon
      (ApoE epsilon2,3,4), Angiotensin-Converting Enzyme insertion/deletion (ACE I/D),
      methylenetetrahydrofolate reductase (MTHFR) C677T, C-reactive protein (CRP)
      286C>A>T, and interleukin-1beta (IL-1beta) C-511T. We found that larger WMH
      volume was associated with advanced age, hypertension, and elevated levels of
      homocysteine and CRP but not with low-density lipoprotein levels. Homozygotes for
      IL-1beta-511T allele and carriers of CRP-286T allele that are associated with
      increased inflammatory response had larger WMH than the other allelic
      combinations. Carriers of the APOE epsilon2 allele had larger frontal WMH than
      epsilon3 homozygotes and epsilon4 carriers did. Thus, in healthy adults, who are
      free of neurological and vascular disease, genetic variants that promote
      inflammation and elevated levels of vascular risk biomarkers can contribute to
      brain abnormalities. This article is part of a Special Issue entitled: Imaging
      Brain Aging and Neurodegenerative disease.

PMID- 21889593
TI  - The Rab1 GTPase of Sciaenops ocellatus modulates intracellular bacterial
      infection.
AB  - The Rab family proteins belong to the Ras-like GTPase superfamily and play
      important roles in intracellular membrane trafficking. To date no studies on fish
      Rab have been documented, though rab-like sequences have been found in a number
      of teleosts. In this study, we identified and analyzed a Rab homologue, SoRab1,
      from red drum, Sciaenops ocellatus. The cDNA of SoRab1 contains a 5'-
      untranslated region (UTR) of 358 bp, an open reading frame (ORF) of 612 bp, and a
      3'-UTR of 265 bp. The ORF encodes a putative protein of 203 residues, which
      shares 92-99% overall sequence identities with the Rab1 from fish, human, and
      mouse. SoRab1 possesses a typical Rab1 GTPase domain with the conserved G box
      motifs and the switch I and switch II regions. Recombinant SoRab1 purified from
      Escherichia coli exhibits apparent GTPase activity. Quantitative real time RT-PCR
      analysis showed that SoRab1 expression was detected in a number of tissues, with
      the lowest expression found in blood and highest expression found in muscle.
      Bacterial and lipopolysaccharide challenges significantly upregulated SoRab1
      expression in liver, kidney, and spleen in time-dependent manners. Transient
      overexpression of SoRab1 in primary hepatocytes reduced intracellular bacterial
      infection, whereas interference with SoRab1 expression by RNAi enhanced
      intracellular bacterial invasion. These results provide the first indication that
      a fish Rab1 GTPase, SoRab1, regulates intracellular bacterial infection and thus
      is likely to play a role in bacteria-induced host immune defense.

PMID- 21889594
TI  - Association between language and spatial laterality and cognitive ability: an
      fMRI study.
AB  - The interaction between language and spatial laterality and its association with
      cognitive ability was explored in a group of 42 right-handers and 40 left-handers
      using functional magnetic resonance imaging. Cognitive ability measures including
      working memory, verbal comprehension and perceptual organisation were assessed
      using the Wechsler Adult Intelligence Scale (version III). Left-handers show
      lower working memory scores than right-handers. Increased rightward language
      laterality is also associated with decreased working memory performance, which we
      suggest is related to the involvement of the left inferior frontal gyrus in
      subvocal rehearsal during working memory tasks. The interaction between language
      and spatial laterality is associated with performance on verbal comprehension and
      perceptual organisation, such that when language and spatial laterality are
      dissociated between the hemispheres a significant increase in verbal
      comprehension and perceptual organisation performance is found. There is a
      decrease in performance on the verbal comprehension and perceptual organisation
      subtests when language and spatial processing are associated to the same
      hemisphere (i.e. both lateralised to the right hemisphere or both lateralised to
      the left). This interaction is interpreted in relation to the 'hemispheric
      crowding' hypothesis, which proposes increased cognitive ability when language
      and spatial laterality are dissociated.

PMID- 21889595
TI  - Conflict caused by visual feedback modulates activation in somatosensory areas
      during movement execution.
AB  - The role of sensory information in motor control has been studied, but the
      cortical processing underlying cross-modal relationship between visual and
      somatosensory information for movement execution remains a matter of debate.
      Visual estimates of limb positions are congruent with proprioceptive estimates
      under normal visual conditions, but a mismatch between the watched and felt
      movement of the hand disrupts motor execution. We investigated whether activation
      in somatosensory areas was affected by the discordance between the intended and
      an executed action. Subjects performed self-paced thumb movement of the left hand
      under normal visual and mirror conditions. The Mirror condition provided a non
      veridical and unexpected visual feedback. The results showed activity in the
      primary somatosensory area to be inhibited and activity in the secondary
      somatosensory area (SII) to be enhanced with voluntary movement, and neural
      responses in the SII and parietal cortex were strongly affected by the unexpected
      visual feedback. These results provide evidence that the visual information plays
      a crucial role in activation in somatosensory areas during motor execution. A
      mechanism that monitors sensory inputs and motor outputs congruent with current
      intension is necessary to control voluntary movement.

PMID- 21889596
TI  - The trajectory of recovery and the inter-relationships of symptoms, activity and
      participation in the first year following total hip and knee replacement.
AB  - OBJECTIVE: Primary total hip (THR) and knee (TKR) replacement outcomes typically
      include pain and function with a single time of follow-up post-surgery. This
      research evaluated the trajectory of recovery and inter-relationships within and
      across time of physical impairments (PI) (e.g., symptoms), activity limitations
      (AL), and social participation restrictions (PR) in the year following THR and
      TKR for osteoarthritis. DESIGN: Participants (hip: n=437; knee: 494) completed
      measures pre-surgery and at 2 weeks, 1, 3, 6 and 12 months post-surgery. These
      included PI (Hip Disability and Osteoarthritis Outcome Score (HOOS)/Knee Injury
      and Osteoarthritis Outcome Score (KOOS) symptoms and Chronic Pain Grade); AL
      (HOOS/KOOS activities of daily living and sports/leisure activities); and, PR
      (Late Life Disability and the Calderdale community mobility). Repeated measures
      analysis of variance (RANOVA) was used to evaluate the trajectory of recovery of
      outcomes and the inter-relationships of PI, AL and PR were evaluated using path
      analysis. All analyses were adjusted for age, sex, obesity, THR/TKR, low back
      pain and mood. RESULTS: THR: age 31-86 years with 55% female; TKR: age 35-88
      years with 65% female. Significant improvements in outcomes were observed over
      time. However, improvements were lagged over time with earlier improvements in PI
      and AL and later improvements in PR. Within and across time, PI was associated
      with AL and AL was associated with PR. The magnitude of these inter-relationships
      varied over time. CONCLUSION: Given the lagged inter-relationship of PI, AL and
      PR, the provision and timing of interventions targeting all constructs are
      critical to maximizing outcome. Current care pathways focusing on short-term
      follow-up with limited attention to social and community participation should be
      re-evaluated.

PMID- 21889597
TI  - Gene expression associated with vegetative incompatibility in Amylostereum
      areolatum.
AB  - In filamentous fungi, vegetative compatibility among individuals of the same
      species is determined by the genes encoded at the heterokaryon incompatibility
      (het) loci. The hyphae of genetically similar individuals that share the same
      allelic specificities at their het loci are able to fuse and intermingle, while
      different allelic specificities at the het loci result in cell death of the
      interacting hyphae. In this study, suppression subtractive hybridization (SSH)
      followed by pyrosequencing and quantitative reverse transcription PCR were used
      to identify genes that are selectively expressed when vegetatively incompatible
      individuals of Amylostereum areolatum interact. The SSH library contained genes
      associated with various cellular processes, including cell-cell adhesion, stress
      and defence responses, as well as cell death. Some of the transcripts encoded
      proteins that were previously implicated in the stress and defence responses
      associated with vegetative incompatibility. Other transcripts encoded proteins
      known to be associated with programmed cell death, but have not previously been
      linked with vegetative incompatibility. Results of this study have considerably
      increased our knowledge of the processes underlying vegetative incompatibility in
      Basidiomycetes in general and A. areolatum in particular.

PMID- 21889598
TI  - Diet affects resting, but not basal metabolic rate of normothermic Siberian
      hamsters acclimated to winter.
AB  - We examined the effect of different dietary supplements on seasonal changes in
      body mass (m(b)), metabolic rate (MR) and nonshivering thermogenesis (NST)
      capacity in normothermic Siberian hamsters housed under semi-natural conditions.
      Once a week standard hamster food was supplemented with either sunflower and flax
      seeds, rich in polyunsaturated fatty acids (FA), or mealworms, rich in saturated
      and monounsaturated FA. We found that neither of these dietary supplements
      affected the hamsters' normal winter decrease in m(b) and fat content nor their
      basal MR or NST capacity. NST capacity of summer-acclimated hamsters was lower
      than that of winter-acclimated ones. The composition of total body fat reflected
      the fat composition of the dietary supplements. Resting MR below the lower
      critical temperature of the hamsters, and their total serum cholesterol
      concentration were lower in hamsters fed a diet supplemented with mealworms than
      in hamsters fed a diet supplemented with seeds. These results indicate that in
      mealworm-fed hamsters energy expenditure in the cold is lower than in animals
      eating a seed-supplemented diet, and that the degree of FA unsaturation of diet
      affects energetics of heterotherms, not only during torpor, but also during
      normothermy.

PMID- 21889599
TI  - Triacylglycerol catabolism in the prawn Macrobrachium borellii (Crustacea:
      Palaemoniade).
AB  - While invertebrates store neutral lipids as their major energy source, little is
      known about triacylglycerol (TAG) class composition and their differential
      catabolism in aquatic arthropods. This study focuses on the composition of the
      main energy source and its catabolism by lipase from the midgut gland
      (hepatopancreas) of the crustacean Macrobrachium borellii. Silver-ion thin-layer
      chromatography of prawn large TAG deposit (80% of total lipids) and its
      subsequent fatty acid analysis by gas chromatography allowed the identification
      of 4 major fractions. These are composed of fatty acids of decreasing
      unsaturation and carbon chain length, the predominant being 18:1n-9. Fraction I,
      the most unsaturated one, contained mainly 20:5n-3; fraction II 18:2n-6; fraction
      III 18:1n-9 while the most saturated fraction contained mostly 16:0.
      Hepatopancreas main lipase (Mr 72 kDa) cross-reacted with polyclonal antibodies
      against insect lipase, was not dependent on the presence of Ca(2+) and had an
      optimum activity at 40 degrees C and pH 8.0. Kinetic analysis showed a Michaelis
      Menten behavior. A substrate competition assay evidenced lipase specificity
      following the order: 18:1n-9-TAG>PUFA-enriched-TAG>16:0-TAG different from that
      in vertebrates. These data indicate there is a reasonable correspondence between
      the fatty acid composition of TAG and the substrate specificity of lipase, which
      may be an important factor in determining which fatty acids are mobilized during
      lipolysis for oxidation in crustaceans.

PMID- 21889600
TI  - In vitro lipid transfer between lipoproteins and midgut-diverticula in the spider
      Polybetes pythagoricus.
AB  - It has been already reported that most hemolymphatic lipids in the spider
      Polybetes pythagoricus are transported by HDL1 and VHDL lipoproteins. We studied
      in vitro the lipid transfer among midgut-diverticula (M-diverticula), and either
      hemolymph or purified lipoproteins as well as between hemolymphatic lipoproteins.
      M-diverticula and hemolymph were labeled by in vivo (14)C-palmitic acid
      injection. In vitro incubations were performed between M-diverticula and either
      hemolymph or isolated lipoproteins. Hemolymph lipid uptake was associated to HDL1
      (67%) and VHDL (32%). Release from hemolymph towards M-diverticula showed the
      opposite trend, VHDL 75% and HDL1 45%. Isolated lipoproteins showed a similar
      behavior to that observed with whole hemolymph. Lipid transfer between
      lipoproteins showed that HDL1 transfer more (14)C-lipids to VHDL than vice versa.
      Only 38% FFA and 18% TAG were transferred from M-diverticula to lipoproteins,
      while on the contrary 75% and 73% of these lipids, respectively, were taken up
      from hemolymph. A similar trend was observed regarding lipoprotein phospholipids.
      This study supports the hypothesis that HDL1 and hemocyanin-containing VHDL are
      involved in the uptake and release of FFA, phospholipids and triacylglycerols in
      the spider P. pythagoricus. The data support a directional flow of lipids from
      HDL1 and VHDL suggesting a mode of lipid transport between lipoproteins and M
      diverticula.

PMID- 21889601
TI  - Effects of sexual steroids on the expression of foxl2 in Gobiocypris rarus.
AB  - Gobiocypris rarus is an emerging fish model for aquatic toxicology in China as it
      is sensitive to environmental hormone disruptors. Exogenous sex steroids can
      affect sex differentiation and the expression of sex-related genes. Foxl2, a
      member of forkhead-box transcription factor family, is the key gene for ovary
      development and its mutation causes the blepharophimosis ptosis epicanthus
      inversus syndrome in human. We find that two foxl2 genes exist in fish genome,
      one is foxl2, and the other is foxl2b. Here, we reported the isolation and
      expression of foxl2 in G. rarus. G. rarus foxl2 cDNA is 1700bp in length with a
      921bp of open reading frame encoding 306 amino acids containing the typical FH
      domain. Semi-quantitative RT-PCR revealed its predominant expression in the eye,
      brain, gill and gonads. Moreover, the expression level in the ovary was
      significantly higher than that in the testis. Quantitative RT-PCR showed that
      foxl2 was up regulated after treatment with estradiol and was down regulated with
      2-methyl-testosterone. These results suggested that Foxl2 plays an important role
      in female development of G. rarus, foxl2 mRNA expression is regulated by
      downstream sex hormones, and foxl2 can be used as a molecular indicator
      monitoring the environmental endocrine disruptors.

PMID- 21889602
TI  - Induction of ambicoloration by exogenous cortisol during metamorphosis of spotted
      halibut Verasper variegatus.
AB  - Cortisol, the main glucocorticoid in fish, increases during flatfish
      metamorphosis and peaks before the surge of thyroxine. A large body of evidence
      indicates the essential role of thyroxine in flatfish metamorphosis, whereas
      information on cortisol is limited. We administered cortisol to spotted halibut
      Verasper variegatus larvae in order to examine the effect on pigmentation during
      metamorphosis. Administration of 10 MUg cortisol per mL of water from before the
      onset of metamorphosis (stage E) to metamorphic climax (stage G) induced the
      development of adult type pigment cells on the blind side of the metamorphosed
      juveniles and increased the occurrence of ambicolored juveniles. When 10 MUg/mL
      cortisol was administered during stage D, stages E-F, stage G or stage H, only
      the administration during stages E-F induced the development of adult type
      pigment cells on the blind side. In addition, the expression of the gene
      dopachrome tautomerase (dct), a marker of melanoblasts, was enhanced at Stage E
      by cortisol administration. These results clearly indicated, for the first time,
      the enhancement of pigmentation by exogenous high-dose cortisol. Since endogenous
      cortisol is secreted in response to various kinds of stress in rearing
      conditions, these results indicate a possible influence of stress conditions in
      the occurrence of ambicoloration in flatfish.

PMID- 21889603
TI  - O-Acetylated peptidoglycan: controlling the activity of bacterial autolysins and
      lytic enzymes of innate immune systems.
AB  - The O-acetylation of peptidoglycan is now known to occur in 50 different
      bacterial species, both Gram positive and Gram negative, including a number of
      important human pathogens. This modification to the essential cell wall component
      of bacteria provides both a level of control over endogenous autolysins and
      protection from the lysozymes of innate immune systems. In this review, we
      describe the details of the pathways for peptidoglycan O-acetylation that are now
      beginning to emerge and we explore the possibility that the associated enzymes
      may present new candidates for antibacterial targets.

PMID- 21889604
TI  - HIV vaccine: hopes and hurdles.
AB  - The AIDS vaccine development effort has already been facing various scientific
      and economic challenges. The fundamental challenge resides at the level of
      understanding the basic biology of HIV-1 infection and an effective antiviral
      immune response. There is a need to design immunogens that can elicit cross-clade
      neutralizing antibodies (NAbs) along with effective T-cell responses against a
      wide variety of primary HIV isolates. We must exploit the capabilities of the
      vaccine-elicited cytotoxic T cells and the NAb responses in controlling HIV-1
      replication. A coordinated approach is required to understand the intricacies
      involved in the basic immune responses against HIV infection as well as the cross
      clade effectiveness of an AIDS vaccine.

PMID- 21889605
TI  - Where do innovative drugs come from?

PMID- 21889606
TI  - Study on X-ray-induced apoptosis and chromosomal damage in G2 human lymphocytes
      in the presence of pifithrin-alpha, an inhibitor of p53.
AB  - The aim of this study is to investigate the role of the cell-cycle phase in cells
      exposed to radiation and chemicals in relation to the cellular response. The
      analysis was focused on the G2 cell-cycle phase, exploring the impact of p53
      inhibition in human lymphocytes irradiated with X-rays in the presence or absence
      of pifithrin-alpha (PFT-alpha), a p53-specific inhibitor. Lymphocytes, 44h after
      stimulation to proliferate, were X-irradiated with 0.5Gy both in the presence or
      the absence of PFT-alpha and post-treated with a pulse of 5-bromodeoxyuridine
      (BrdUrd) to distinguish cells in the S- or G2-phase at the moment of irradiation.
      At early sampling times after X-ray exposure the following parameters were
      analysed: cellular proliferation, apoptosis, chromosomal aberrations and p53
      expression. The results show an enhancement of apoptotic cells in G2 at early
      sampling times after irradiation and no differences in terms of chromosomal
      aberration induction both in cells treated with X-rays alone and in cells treated
      with X-rays plus PFT-alpha. Expression of p53 was not detectable at all recovery
      times. The results suggest a p53-independent apoptotic pathway acting at early
      times after X-ray exposure in G2 lymphocytes. Furthermore, the same yield of X
      ray-induced chromatid breaks was observed both in the presence or absence of PFT
      alpha implying that in G2 X-irradiated lymphocytes this inhibitor of the p53
      protein does not affect DNA repair.

PMID- 21889607
TI  - In vitro and in vivo induction of chromosome aberrations by alpha- and beta
      zearalenols: comparison with zearalenone.
AB  - Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by Fusarium
      fungi. It contaminates different components of the food chain and can cause
      serious economic and public health problems. The major metabolites of ZEN in
      various animal species are alpha- and beta-zearalenol (alpha-, beta-ZOL). Some in
      vivo studies have shown that these two metabolites are as toxic as the mother
      molecule (ZEN), but other investigations have demonstrated that alpha- and beta
      ZOL are less toxic than ZEN. Thus, the aim of the present study was to evaluate
      cytotoxicity and genotoxicity of alpha- and beta-ZOL in vivo, in mouse bone
      marrow cells and in vitro, in cultured HeLa cells, and to compare it with ZEN.
      ZEN showed the same cytotoxicity as alpha-ZOL and both are more cytotoxic than
      beta-ZOL. Genotoxicity of ZEN and its derivatives was assessed by the chromosome
      aberration assay. Our results show that ZEN as well as alpha- and beta-ZOL
      increased the percentage of chromosome aberrations in mouse bone-marrow cells and
      in HeLa cells. In the two systems, ZEN and alpha-ZOL exhibited the same range of
      genotoxicity and both were more genotoxic than beta-ZOL. Furthermore, our results
      show that either ZEN or its two metabolites inhibited cell viability in a dose
      dependent manner. We conclude that biotransformation of ZEN may be considered as
      only a partial detoxification pathway since the resulting metabolites remain
      relatively toxic.

PMID- 21889608
TI  - The LXR agonist GW3965 increases apoA-I protein levels in the central nervous
      system independent of ABCA1.
AB  - Lipoprotein metabolism in the central nervous system (CNS) is based on high
      density lipoprotein-like particles that use apoE as their predominant
      apolipoprotein rather than apoA-I. Although apoA-I is not expressed in astrocytes
      and microglia, which produce CNS apoE, apoA-I is reported to be expressed in
      porcine brain capillary endothelial cells and also crosses the blood-brain
      barrier (BBB). These mechanisms allow apoA-I to reach concentrations in
      cerebrospinal fluid (CSF) that are approximately 0.5% of its plasma levels.
      Recently, apoA-I has been shown to enhance cognitive function and reduce
      cerebrovascular amyloid deposition in Alzheimer's Disease (AD) mice, raising
      questions about the regulation and function of apoA-I in the CNS. Peripheral apoA
      I metabolism is highly influenced by ABCA1, but less is known about how ABCA1
      regulates CNS apoA-I. We report that ABCA1 deficiency leads to greater retention
      of apoA-I in the CNS than in the periphery. Additionally, treatment of
      symptomatic AD mice with GW3965, an LXR agonist that stimulates ABCA1 expression,
      increases apoA-I more dramatically in the CNS compared to the periphery.
      Furthermore, GW3965-mediated up-regulation of CNS apoA-I is independent of ABCA1.
      Our results suggest that apoA-I may be regulated by distinct mechanisms on either
      side of the BBB and that apoA-I may serve to integrate peripheral and CNS lipid
      metabolism. This article is part of a Special Issue entitled Advances in High
      Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945
      2010).

PMID- 21889609
TI  - Quantitative and qualitative analyses of the SNRPN gene using real-time PCR with
      melting curve analysis.
AB  - Prader-Willi syndrome and Angelman syndrome are distinct neurodevelopmental
      disorders that are associated with the deletion of the chromosomal 15q11-13
      region or uniparental disomy of chromosome 15. In this article, we applied SYBR
      Green I-based real-time PCR and melting curve analysis assay for rapid genotyping
      of the small nuclear ribonucleoprotein polypeptide N (SNRPN) gene methylation
      status and for detecting aberrations in copy number in a single tube. A single
      pair of primers was designed to create a 357 bp fragment containing the cytosine
      phosphodiester guanine islands in the SNRPN promoter and to amplify both
      unmethylated and methylated sequences. Genotypes were identified based on the TC
      value for copy number changes and the characteristic melting temperature of
      methylated cytosine phosphodiester guanine. Genotyping of SNRPN was performed on
      blood samples of 20 individuals with Prader-Willi syndrome, 3 individuals with
      Angelman syndrome, and 20 unaffected individuals. The promoter methylation status
      and the copy number changes were successfully determined and compared with
      standard methylation-specific PCR, and were validated by multiplex ligation
      dependent probe amplification. This single-tube, SYBR Green I, real-time PCR with
      melting curve assay is rapid, reliable, sensitive, and easy to perform. It is
      suitable for high-throughput analysis as an alternative technique for
      quantitative and qualitative analysis of target genes.

PMID- 21889610
TI  - Diagnostic testing for IDH1 and IDH2 variants in acute myeloid leukemia an
      algorithmic approach using high-resolution melting curve analysis.
AB  - Isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations and polymorphism are
      reported in 5% to 15% of acute myeloid leukemia (AML) cases, with G105 and R132
      of IDH1 and R140 and R172 of IDH2 known to be clinically significant. Current
      Sanger sequencing assays to detect IDH mutations are labor intensive and not cost
      effective for clinical testing of low-frequency mutations. Therefore, we
      developed clinical assays using high-resolution melting (HRM) analysis to screen
      for all four variants listed above, followed by Sanger sequencing confirmation.
      The sensitivities of the assays were 7.3% and 7.9% for the detection of IDH2 and
      IDH1 variants, respectively, against the background of wild-type transcripts.
      Comparison of HRM to Sanger sequencing on 146 AML bone marrow samples for
      validation showed near-perfect concordance for all positive and negative results
      for IDH1 (98%) and IDH2 (94%). Postvalidation clinical implementation of upfront
      HRM screening (N = 106), using a more conservative algorithm to avoid false
      negative results, reduced the number of Sanger sequencing tests by 73% (IDH1) and
      78% (IDH2). Of the variant calls made by HRM in postvalidation clinical samples,
      Sanger confirmed the presence of a variant in 62% (IDH1) and 44% (IDH2) of the
      samples. In conclusion, our HRM assays are rapid, convenient, and versatile
      assays for screening and confirmation of alterations in IDH1 and IDH2.

PMID- 21889611
TI  - Novel, improved sample preparation for rapid, direct identification from positive
      blood cultures using matrix-assisted laser desorption/ionization time-of-flight
      (MALDI-TOF) mass spectrometry.
AB  - Matrix-assisted laser desorption ionization time-of-flight mass spectrometry
      (MALDI-TOF MS) is widely used for rapid and reliable identification of bacteria
      and yeast grown on agar plates. Moreover, MALDI-TOF MS also holds promise for
      bacterial identification from blood culture (BC) broths in hospital laboratories.
      The most important technical step for the identification of bacteria from
      positive BCs by MALDI-TOF MS is sample preparation to remove blood cells and host
      proteins. We present a method for novel, rapid sample preparation using
      differential lysis of blood cells. We demonstrate the efficacy and ease of use of
      this sample preparation and subsequent MALDI-TOF MS identification, applying it
      to a total of 500 aerobic and anaerobic BCs reported to be positive by a Bactec
      9240 system. In 86.5% of all BCs, the microorganism species were correctly
      identified. Moreover, in 18/27 mixed cultures at least one isolate was correctly
      identified. A novel method that adjusts the score value for MALDI-TOF MS results
      is proposed, further improving the proportion of correctly identified samples.
      The results of the present study show that the MALDI-TOF MS-based method allows
      rapid (<20 minutes) bacterial identification directly from positive BCs and with
      high accuracy.

PMID- 21889612
TI  - Comparison of QIAsymphony automated and QIAamp manual DNA extraction systems for
      measuring Epstein-Barr virus DNA load in whole blood using real-time PCR.
AB  - Automated and manual extraction systems have been used with real-time PCR for
      quantification of Epstein-Barr virus [human herpesvirus 4 (HHV-4)] DNA in whole
      blood, but few studies have evaluated relative performances. In the present
      study, the automated QIAsymphony and manual QIAamp extraction systems (Qiagen,
      Valencia, CA) were assessed using paired aliquots derived from clinical whole
      blood specimens and an in-house, real-time PCR assay. The detection limits using
      the QIAsymphony and QIAamp systems were similar (270 and 560 copies/mL,
      respectively). For samples estimated as having >=10,000 copies/mL, the intrarun
      and interrun variations were significantly lower using QIAsymphony (10.0% and
      6.8%, respectively), compared with QIAamp (18.6% and 15.2%, respectively); for
      samples having <=1000 copies/mL, the two variations ranged from 27.9% to 43.9%
      and were not significantly different between the two systems. Among 68 paired
      clinical samples, 48 pairs yielded viral loads >=1000 copies/mL under both
      extraction systems. Although the logarithmic linear correlation from these
      positive samples was high (r(2) = 0.957), the values obtained using QIAsymphony
      were on average 0.2 log copies/mL higher than those obtained using QIAamp. Thus,
      the QIAsymphony and QIAamp systems provide similar EBV DNA load values in whole
      blood.

PMID- 21889613
TI  - Activating transcription factor 3 and reactive astrocytes following optic nerve
      injury in zebrafish.
AB  - Nerve regeneration in the central nervous system is restricted in mammals, but
      fish and amphibians show amazing resiliency following injury to the central
      nervous system. We have examined the response of zebrafish (Danio rerio) to optic
      nerve injury to try to understand the differences between fish and mammals that
      enable fish to regenerate their optic nerves following crushing and severing. In
      previous work, we have shown that activating transcription factor 3 (atf3) is
      expressed at higher levels following optic nerve injury. Here we use a polyclonal
      anti-ATF3 antibody, anti-cytokeratin (KRT-18) and anti-bystin (BYSL) antibodies
      to show that Atf3 and Bysl colocalize with cytokeratin-expressing astrocytes in
      the optic nerve following severing. Furthermore, anti-ATF3 antibodies fail to
      colocalize with GFP in transgenic zebrafish expressing EGFP in astrocytes
      Tg(gfap:GFP) or oligodendrocytes Tg(olig2:EGFP). Interestingly, labeling of Atf3
      was detected in retinal ganglion cell axons in both the nerve fiber layer and the
      optic nerve on the injured side. Finally, optic nerve astrocytes labeled with
      anti-bystin antibodies showed evidence of hypertrophy, suggesting that fish
      astrocytes in the optic nerve raise a bona fide reactive response to injury even
      though they do not express glial fibrillary acidic protein.

PMID- 21889614
TI  - In vitro evaluation of co-exposure of arsenium and an organic nanomaterial
      (fullerene, C60) in zebrafish hepatocytes.
AB  - Taking into account the concept of the "Trojan Horse", where contaminants may
      have its entry into specific organs potentiated by its association with
      nanomaterials, the aim of this study was to analyze the joint toxic effects
      induced by an organic nanomaterial, fullerene (C(60)) with the metalloid arsenic
      (As(III)). Hepatocytes of zebrafish Danio rerio were exposed to As(III) (2.5 or
      100 MUM), C(60) or As+C(60) for 4h, not altering cells viability. Intracellular
      reactive oxygen species concentration was reduced in cells exposed only to the
      C(60) (1mg/L) and in the treatment of 100 MUM As(III)+C(60). Co-exposure with
      C(60) abolished the peak of the antioxidant glutathione (GSH) registered in cells
      exposed to the lowest As(III) concentration (2.5 MUM). A similar result was
      observed in terms of lipid damage (TBARS). Total antioxidant capacity was
      significantly higher at both As(III) concentrations co-exposed to C(60) when
      compared with the control group. Activity of glutathione-S-transferase omega, a
      limiting enzyme in the methylation pathway of As(III), was reduced in the 100 MUM
      As(III)+C(60) treatment. Cells co-exposed to C(60) had a significantly higher
      accumulation of As(III), showing a "Trojan Horse" effect which did not result in
      higher cell toxicity. Instead, co-exposure of As(III) with C(60) showed to reduce
      cellular injury.

PMID- 21889615
TI  - Method selection and adaptation for distributed monitoring of infectious diseases
      for syndromic surveillance.
AB  - BACKGROUND: Automated surveillance systems require statistical methods to
      recognize increases in visit counts that might indicate an outbreak. In prior
      work we presented methods to enhance the sensitivity of C2, a commonly used time
      series method. In this study, we compared the enhanced C2 method with five
      regression models. METHODS: We used emergency department chief complaint data
      from US CDC BioSense surveillance system, aggregated by city (total of 206
      hospitals, 16 cities) during 5/2008-4/2009. Data for six syndromes (asthma,
      gastrointestinal, nausea and vomiting, rash, respiratory, and influenza-like
      illness) was used and was stratified by mean count (1-19, 20-49, >=50 per day)
      into 14 syndrome-count categories. We compared the sensitivity for detecting
      single-day artificially-added increases in syndrome counts. Four modifications of
      the C2 time series method, and five regression models (two linear and three
      Poisson), were tested. A constant alert rate of 1% was used for all methods.
      RESULTS: Among the regression models tested, we found that a Poisson model
      controlling for the logarithm of total visits (i.e., visits both meeting and not
      meeting a syndrome definition), day of week, and 14-day time period was best.
      Among 14 syndrome-count categories, time series and regression methods produced
      approximately the same sensitivity (<5% difference) in 6; in six categories, the
      regression method had higher sensitivity (range 6-14% improvement), and in two
      categories the time series method had higher sensitivity. DISCUSSION: When
      automated data are aggregated to the city level, a Poisson regression model that
      controls for total visits produces the best overall sensitivity for detecting
      artificially added visit counts. This improvement was achieved without increasing
      the alert rate, which was held constant at 1% for all methods. These findings
      will improve our ability to detect outbreaks in automated surveillance system
      data.

PMID- 21889616
TI  - Distinct expression patterns of dickkopf genes during late embryonic development
      of Danio rerio.
AB  - Dickkopf (dkk) genes belong to the family of secreted wnt-inhibitors with
      conserved cysteine-rich domains. In contrast to the prototype dkk1, dkk3 does not
      modulate canonical Wnt/beta-catenin signalling. Until now, neither functions nor
      interaction partners of dkk3 in lower vertebrates have been described. In this
      study we cloned two dkk3 homologues dkk3a(dkk3l) and dkk3b(dkk3) and a dkk1
      homologue dkk1a of the zebrafish and studied their expression patterns during
      embryonic development in comparison to the known dkk1b gene. Moreover, mutants
      with defects in hedgehog signalling (smo), notch (mib) signalling, nodal
      signalling (Zoep) or retinoic acid synthesis (neckless) were analyzed for changes
      in dkk3 gene expression. In situ hybridization analyses showed a dynamic
      expression of dkk1a and dkk1b primarily in epidermal structures of the otic
      vesicle, lens, branchial arches and fin folds. While dkk1a was expressed mainly
      in deep tissues, dkk1b expression was mainly found in protrusions at the outer
      surface of the branchial arch epidermis. In contrast, dkk3 genes showed
      expression in different tissues. Strong signals for dkk3a(dkk3l) were present in
      various neuronal structures of the head, whereas dkk3b(dkk3) expression was
      restricted mainly to endocrine cells of the pancreas and to the brachial arches.
      In summary, both dkk3 genes display a unique and distinct expression pattern in
      late embryonic development, pointing to a specific role during neuronal and
      pancreatic cell differentiation.

PMID- 21889617
TI  - Quantification and molecular characterization of the feline leukemia virus A
      receptor.
AB  - Virus receptors and their expression patterns on the cell surface determine the
      cell tropism of the virus, host susceptibility and the pathogenesis of the
      infection. Feline thiamine transport protein 1 (fTHTR1) has been identified as
      the receptor for feline leukemia virus (FeLV) A. The goal of the present study
      was to develop a quantitative, TaqMan real-time PCR assay to investigate fTHTR1
      mRNA expression in tissues of uninfected and FeLV-infected cats, cats of
      different ages, in tumor tissues and leukocyte subsets. Moreover, the receptor
      was molecularly characterized in different feline species. fTHTR1 mRNA expression
      was detected in all 30 feline tissues investigated, oral mucosa scrapings and
      blood. Importantly, identification of significant differences in fTHTR1
      expression relied on normalization with an appropriate reference gene. The lowest
      levels were found in the blood, whereas high levels were measured in the oral
      mucosa, salivary glands and the musculature. In the blood, T lymphocytes showed
      significantly higher fTHTR1 mRNA expression levels than neutrophil granulocytes.
      In vitro activation of peripheral blood mononuclear cells with concanavalin A
      alone or followed by interleukin-2 led to a transient increase of fTHTR1 mRNA
      expression. In the blood, but not in the examined tissues, FeLV-infected cats
      tended to have lower fTHTR1 mRNA levels than uninfected cats. The fTHTR1 mRNA
      levels were not significantly different between tissues with lymphomas and the
      corresponding non-neoplastic tissues. fTHTR1 was highly conserved among different
      feline species (Iberian lynx, Asiatic and Indian lion, European wildcat,
      jaguarundi, domestic cat). In conclusion, while ubiquitous fTHTR1 mRNA expression
      corresponded to the broad target tissue range of FeLV, particularly high fTHTR1
      levels were found at sites of virus entry and shedding. The differential
      susceptibility of different species to FeLV could not be attributed to variations
      in the fTHTR1 sequence.

PMID- 21889618
TI  - Differential association of KIR gene loci to risk of malaria in ethnic groups of
      Assam, Northeast India.
AB  - Receptors encoded within the Natural Killer Cell (NKC) complex and Killer
      Immunoglobulin like (KIRs) genomic regions have been suggested to influence
      malaria pathogenesis and infection susceptibility. We have examined KIR locus in
      relation to risk of infection and disease in Tea tribes (TT) of Austro Asiatic
      affinity and Tibeto-Burman (TB) populations from malaria endemic regions of
      Assam. Consistent with differences in their genetic background, KIR gene loci
      frequencies differed in studied groups. Surprisingly, KIR3DS1 frequency in TT was
      low (17%) and comparable to that reported from African populations. KIR3DL1
      frequency was positively associated with malaria severity (Pearson phi, R(2) =
      0.297 p = 0.006) and logistic regression modelling predicted KIR3DL1 as a risk
      factor in complicated malaria [Odds Ratio (95% C.I)] = [6.39 (1.34-30.60)]. An
      interaction between ethnicity and KIR3DL1 was also seen where higher proportion
      of KIR3DL1 positive and complicated malaria patients belonged to Tea tribes (p =
      0.009). Notably, four activating genes protected from frequent malaria (p = 0.02)
      while six activating genes enhanced the risk of complicated malaria (p = 0.05).
      Combination of KIR2DS4, KIR2DS4del, KIR2DS5 negatively influenced disease outcome
      in Tea tribes (p = 0.048) but not in Tibeto-Burman. In conclusion our data
      indicates KIR gene loci differentially influenced malaria outcome in Tea tribes
      and Tibeto-Burman and that four activating genes appeared to provide optimal
      activation that protected from frequent episodes of malaria. Our data also
      indicated KIR3DS1 to be an ancestral genotype, maintained at low frequency
      possibly by malaria in the Austro Asiatic tribes.

PMID- 21889619
TI  - Genetic variation of the alpha subunit of the epithelial Na+ channel influences
      exhaled Na+ in healthy humans.
AB  - Epithelial Na(+) channels (ENaC) are located in alveolar cells and are important
      in beta(2)-adrenergic receptor-mediated lung fluid clearance through the removal
      of Na(+) from the alveolar airspace. Previous work has demonstrated that genetic
      variation of the alpha subunit of ENaC at amino acid 663 is important in channel
      function: cells with the genotype resulting in alanine at amino acid 663 (A663)
      demonstrate attenuated function when compared to genotypes with at least one
      allele encoding threonine (T663, AT/TT). We sought to determine the influence of
      genetic variation at position 663 of ENaC on exhaled Na(+) in healthy humans.
      Exhaled Na(+) was measured in 18 AA and 13 AT/TT subjects (age=27+/-8 years vs.
      30+/-10 years; ht.=174+/-12 cm vs. 171+/-10 cm; wt.=68+/-12 kg vs. 73+/-14 kg;
      BMI=22+/-3 kg/m(2) vs. 25+/-4 kg/m(2), mean+/-SD, for AA and AT/TT,
      respectively). Measurements were made at baseline and at 30, 60 and 90 min
      following the administration of a nebulized beta(2)-agonist (albuterol sulfate,
      2.5 mg diluted in 3 ml normal saline). The AA group had a higher baseline level
      of exhaled Na(+) and a greater response to beta(2)-agonist stimulation
      (baseline=3.1+/-1.8 mmol/l vs. 2.3+/-1.5 mmol/l; 30 min-post=2.1+/-0.7 mmol/l vs.
      2.2+/-0.8 mmol/l; 60 min-post=2.0+/-0.5 mmol/l vs. 2.3+/-1.0 mmol/l; 90 min
      post=1.8+/-0.8 mmol/l vs. 2.6+/-1.5 mmol/l, mean+/-SD, for AA and AT/TT,
      respectively, p<0.05). The results are consistent with the notion that genetic
      variation of ENaC influences beta(2)-adrenergic receptor stimulated Na(+)
      clearance in the lungs, as there was a significant reduction in exhaled Na(+)
      over time in the AA group.

PMID- 21889621
TI  - Base-metal dental casting alloy biocompatibility assessment using a human-derived
      three-dimensional oral mucosal model.
AB  - Nickel-chromium (Ni-Cr) alloys used in fixed prosthodontics have been associated
      with type IV Ni-induced hypersensitivity. We hypothesised that the full-thickness
      human-derived oral mucosa model employed for biocompatibility testing of base
      metal dental alloys would provide insights into the mechanisms of Ni-induced
      toxicity. Primary oral keratinocytes and gingival fibroblasts were seeded onto
      AllodermTM and maintained until full thickness was achieved prior to Ni-Cr and
      cobalt-chromium (Co-Cr) alloy disc exposure (2-72 h). Biocompatibility assessment
      involved histological analyses with cell viability measurements, oxidative stress
      responses, inflammatory cytokine expression and cellular toxicity analyses.
      Inductively coupled plasma mass spectrometry analysis determined elemental ion
      release levels. We detected adverse morphology with significant reductions in
      cell viability, significant increases in oxidative stress, inflammatory cytokine
      expression and cellular toxicity for the Ni-Cr alloy-treated oral mucosal models
      compared with untreated oral mucosal models, and adverse effects were increased
      for the Ni-Cr alloy that leached the most Ni. Co-Cr demonstrated significantly
      enhanced biocompatibility compared with Ni-Cr alloy-treated oral mucosal models.
      The human-derived full-thickness oral mucosal model discriminated between dental
      alloys and provided insights into the mechanisms of Ni-induced toxicity,
      highlighting potential clinical relevance.

PMID- 21889620
TI  - Opposing influences by subsite -1 and subsite +1 residues on relative
      xylopyranosidase/arabinofuranosidase activities of bifunctional beta-D
      xylosidase/alpha-L-arabinofuranosidase.
AB  - Conformational inversion occurs 7-8kcal/mol more readily in furanoses than
      pyranoses. This difference is exploited here to probe for active-site residues
      involved in distorting pyranosyl substrate toward reactivity. Spontaneous
      glycoside hydrolysis rates are ordered 4-nitrophenyl-alpha-l-arabinofuranoside
      (4NPA)>4-nitrophenyl-beta-d-xylopyranoside (4NPX)>xylobiose (X2). The
      bifunctional beta-d-xylosidase/alpha-l-arabinofuranosidase exhibits the opposite
      order of reactivity, illustrating that the enzyme is well equipped in using
      pyranosyl groups of natural substrate X2 in facilitating glycoside hydrolysis.
      Probing the roles of all 17 active-site residues by single-site mutation to
      alanine and by changing both moieties of substrate demonstrates that the
      mutations of subsite -1 residues decrease the ratio k(cat)(4NPX/4NPA), suggesting
      that the native residues support pyranosyl substrate distortion, whereas the
      mutations of subsite +1 and the subsite -1/+1 interface residues increase the
      ratio k(cat)(4NPX/4NPA), suggesting that the native residues support other
      factors, such as C1 migration and protonation of the leaving group. Alanine
      mutations of subsite -1 residues raise k(cat)(X2/4NPX) and alanine mutations of
      subsite +1 and interface residues lower k(cat)(X2/4NPX). We propose that
      pyranosyl substrate distortion is supported entirely by native residues of
      subsite -1. Other factors leading to the transition state are supported entirely
      by native residues of subsite +1 and interface residues.

PMID- 21889622
TI  - iTRAQ-coupled 2-D LC-MS/MS analysis of cytoplasmic protein profile in Escherichia
      coli incubated with apidaecin IB.
AB  - Apidaecins refer to a series of proline-rich, 18- to 20-residue antimicrobial
      peptides produced by insects. Accumulating evidence that proline-rich
      antimicrobial peptides are not-toxic to human and animal cells makes them
      potential candidates for the development of novel antibiotic drugs. However, the
      mechanism of action was not fully understood. In this study, antibacterial
      mechanism of apidaecins was investigated. iTRAQ-coupled 2-D LC-MS/MS technique
      was utilized to identify altered cytoplasmic proteins of Escherichia coli
      incubated with one isoform of apidaecins--apidaecin IB. The production of the
      chaperonin GroEL and its cofactor GroES, which together form the only essential
      chaperone system in E. coli cytoplasm under all growth conditions, was decreased
      in cells incubated with apidaecin IB. The decreasing of the GroEL-GroES chaperone
      team was further found to be involved in a new antibacterial mechanism of
      apidaecins. Our findings therefore provide important new insights into the
      antibacterial mechanism of apidaecins and perhaps, by extension, for other
      proline-rich antimicrobial peptides.

PMID- 21889623
TI  - The influence of Escherichia coli Hfq mutations on RNA binding and sRNA*mRNA
      duplex formation in rpoS riboregulation.
AB  - The Escherichia coli RNA binding protein Hfq plays an important role in
      regulating mRNA translation through its interactions with small non-coding RNAs
      (sRNAs) and specific mRNAs sites. The rpoS mRNA, which codes for a transcription
      factor, is regulated by several sRNAs. DsrA and RprA enhance translation by
      pairing to a site on this mRNA, while OxyS represses rpoS mRNA translation. To
      better understand how Hfq interacts with these sRNAs and rpoS mRNA, the binding
      of wt Hfq and eleven mutant Hfqs to DsrA, RprA, OxyS and rpoS mRNA was examined.
      Nine of the mutant Hfq had single-residue mutations located on the proximal,
      distal, and outer-edge surfaces of the Hfq hexamer, while two Hfq had truncated C
      terminal ends. Hfq with outer-edge mutations and truncated C-terminal ends
      behaved similar to wt Hfq with regard to binding the sRNAs, rpoS mRNA segments,
      and stimulating DsrA*rpoS mRNA formation. Proximal surface mutations decreased
      Hfq binding to the three sRNAs and the rpoS mRNA segment containing the
      translation initiation region. Distal surface mutations lowered Hfq's affinity
      for the rpoS mRNA segment containing the (ARN)(4) sequence. Strong Hfq binding to
      both rpoS mRNA segments appears to be needed for maximum enhancement of DsrA*rpoS
      mRNA annealing. OxyS bound tightly to Hfq but exhibited weak affinity for rpoS
      mRNA containing the leader region and 75 nt of coding sequence in the absence or
      presence of Hfq. This together with other results suggest OxyS represses rpoS
      mRNA translation by sequestering Hfq rather than binding to rpoS mRNA.

PMID- 21889624
TI  - Method ruggedness studies incorporating a risk based approach: a tutorial.
AB  - This tutorial explains how well thought-out application of design and analysis
      methodology, combined with risk assessment, leads to improved assessment of
      method ruggedness. The authors define analytical method ruggedness as an
      experimental evaluation of noise factors such as analyst, instrument or
      stationary phase batch. Ruggedness testing is usually performed upon transfer of
      a method to another laboratory, however, it can also be employed during method
      development when an assessment of the method's inherent variability is required.
      The use of a ruggedness study provides a more rigorous method for assessing
      method precision than a simple comparative intermediate precision study which is
      typically performed as part of method validation. Prior to designing a ruggedness
      study, factors that are likely to have a significant effect on the performance of
      the method should be identified (via a risk assessment) and controlled where
      appropriate. Noise factors that are not controlled are considered for inclusion
      in the study. The purpose of the study should be to challenge the method and
      identify whether any noise factors significantly affect the method's precision.
      The results from the study are firstly used to identify any special cause
      variability due to specific attributable circumstances. Secondly, common cause
      variability is apportioned to determine which factors are responsible for most of
      the variability. The total common cause variability can then be used to assess
      whether the method's precision requirements are achievable. The approach used to
      design and analyse method ruggedness studies will be covered in this tutorial
      using a real example.

PMID- 21889625
TI  - A review of recent, unconventional applications of ion mobility spectrometry
      (IMS).
AB  - The applications of ion mobility spectrometry (IMS) have grown exponentially
      beyond its uses for explosive, illicit drug and chemical warfare agent monitoring
      in recent years. Instrumental developments including new drift tube materials and
      ionization sources have enabled the manufacturing of more sophisticated and
      affordable IMS equipment for the advantageous analysis of samples with no
      pretreatment. The most recent applications of IMS include quality control and
      cleaning validation procedures in the pharmaceutical industry; determinations of
      contaminants in food samples; clinical analyses of biological fluids;
      environmental analyses of contaminants in gaseous, liquid and solid samples; and
      (bio)process quality control monitoring. Coupling IMS with MS(n) has enabled the
      analysis of very complex samples and the extraction of knowledge unavailable from
      isolated MS measurements, especially in the polymer and petroleomic industries.

PMID- 21889626
TI  - Technology behind commercial devices for blood glucose monitoring in diabetes
      management: a review.
AB  - The blood glucose monitoring devices (BGMDs) are an integral part of diabetes
      management now-a-days. They have evolved tremendously within the last four
      decades in terms of miniaturization, rapid response, greater specificity,
      simplicity, minute sample requirement, painless sample uptake, sophisticated
      software and data management. This article aims to review the developments in the
      technologies behind commercial BGMD, especially those in the areas of
      chemistries, mediators and other components. The technology concerns, on-going
      developments and future trends in blood glucose monitoring (BGM) are also
      discussed.

PMID- 21889627
TI  - Determination of ultra trace arsenic species in water samples by hydride
      generation atomic absorption spectrometry after cloud point extraction.
AB  - Cloud point extraction (CPE) methodology has successfully been employed for the
      preconcentration of ultra-trace arsenic species in aqueous samples prior to
      hydride generation atomic absorption spectrometry (HGAAS). As(III) has formed an
      ion-pairing complex with Pyronine B in presence of sodium dodecyl sulfate (SDS)
      at pH 10.0 and extracted into the non-ionic surfactant, polyethylene glycol tert
      octylphenyl ether (Triton X-114). After phase separation, the surfactant-rich
      phase was diluted with 2 mL of 1M HCl and 0.5 mL of 3.0% (w/v) Antifoam A. Under
      the optimized conditions, a preconcentration factor of 60 and a detection limit
      of 0.008 MUg L(-1) with a correlation coefficient of 0.9918 was obtained with a
      calibration curve in the range of 0.03-4.00 MUg L(-1). The proposed
      preconcentration procedure was successfully applied to the determination of
      As(III) ions in certified standard water samples (TMDA-53.3 and NIST 1643e, a low
      level fortified standard for trace elements) and some real samples including
      natural drinking water and tap water samples.

PMID- 21889628
TI  - Synthesis and application of imprinted polyvinylimidazole-silica hybrid copolymer
      for Pb2+ determination by flow-injection thermospray flame furnace atomic
      absorption spectrometry.
AB  - A novel ion imprinted polyvinylimidazole-silica hybrid copolymer (IIHC) was
      synthesized and used as a selective solid sorbent for Pb(2+) ions
      preconcentration using an on-line solid phase extraction (SPE) system coupled to
      TS-FF-AAS. The ionic hybrid sorbent was prepared using 1-vinylimidazole and 3
      (trimethoxysilyl)propylmethacrylate as monomers, Pb(2+) ions as template,
      tetraethoxysilane as reticulating agent and 2,2'-azobis-isobutyronitrile as
      initiator. The best on-line SPE conditions concerning sorption behavior,
      including sample pH (6.46), buffer concentration (9.0 mmol L(-1)), eluent
      (HNO(3)) concentration (0.5 mol L(-1)) and preconcentration flow rate (4.0 mL
      min(-1)), were optimized by means of full factorial design and Doehlert matrix.
      The analytical curve ranged from 2.5 to 65.0 MUg L(-1) (r=0.999) with limit of
      detection of 0.75 MUg L(-1); the precision (repeatability) calculated as relative
      standard deviation (n=10) was 5.0 and 3.6% for Pb(2+) concentration of 10.0 and
      60.0 MUg L(-1), respectively. From on-line breakthrough curve, column capacity
      was 3.5 mg g(-1). Preconcentration factor (PF), consumptive index (CI) and
      concentration efficiency (CE) were 128.0, 0.16 mL and 25.6 min(-1), respectively.
      The selective performance of the sorbent, based on relative selectivity
      coefficient, was compared to NIC (non imprinted copolymer) for the binary mixture
      Pb(2+)/Cd(2+), Pb(2+)/Cu(2+) and Pb(2+)/Zn(2+). The results showed that ion
      imprinted polyvinylimidazole-silica hybrid polymer had higher selectivity for
      Pb(2+) than NIC at 64.9, 16.0 and 8.8 folds. The developed method was
      successfully applied for highly sensitive and selective Pb(2+) determination in
      different kinds of water samples, parenteral solutions and urine. Accuracy was
      also assessed by analyzing certified reference fish protein (DORM-3) and marine
      sediment (MESS-3 and PACS-2) with satisfactory results.

PMID- 21889629
TI  - Support vector machines in water quality management.
AB  - Support vector classification (SVC) and regression (SVR) models were constructed
      and applied to the surface water quality data to optimize the monitoring program.
      The data set comprised of 1500 water samples representing 10 different sites
      monitored for 15 years. The objectives of the study were to classify the sampling
      sites (spatial) and months (temporal) to group the similar ones in terms of water
      quality with a view to reduce their number; and to develop a suitable SVR model
      for predicting the biochemical oxygen demand (BOD) of water using a set of
      variables. The spatial and temporal SVC models rendered grouping of 10 monitoring
      sites and 12 sampling months into the clusters of 3 each with misclassification
      rates of 12.39% and 17.61% in training, 17.70% and 26.38% in validation, and
      14.86% and 31.41% in test sets, respectively. The SVR model predicted water BOD
      values in training, validation, and test sets with reasonably high correlation
      (0.952, 0.909, and 0.907) with the measured values, and low root mean squared
      errors of 1.53, 1.44, and 1.32, respectively. The values of the performance
      criteria parameters suggested for the adequacy of the constructed models and
      their good predictive capabilities. The SVC model achieved a data reduction of
      92.5% for redesigning the future monitoring program and the SVR model provided a
      tool for the prediction of the water BOD using set of a few measurable variables.
      The performance of the nonlinear models (SVM, KDA, KPLS) was comparable and these
      performed relatively better than the corresponding linear methods (DA, PLS) of
      classification and regression modeling.

PMID- 21889630
TI  - Identification of protein methylation sites by coupling improved ant colony
      optimization algorithm and support vector machine.
AB  - Protein methylation is involved in dozens of biological processes and plays an
      important role in adjusting protein physicochemical properties, conformation and
      function. However, with the rapid increase of protein sequence entering into
      databanks, the gap between the number of known sequence and the number of known
      methylation annotation is widening rapidly. Therefore, it is vitally significant
      to develop a computational method for quick and accurate identification of
      methylation sites. In this study, a novel predictor (Methy_SVMIACO) based on
      support vector machine (SVM) and improved ant colony optimization algorithm
      (IACO) is developed to identify methylation sites. The IACO is utilized to find
      the optimal feature subset and parameter of SVM, while SVM is employed to perform
      the identification of methylation sites. Comparison of the IACO with conventional
      ACO shows that the IACO converges quickly toward the global optimal solution and
      it is more useful tool for feature selection and SVM parameter optimization. The
      performance of Methy_SVMIACO is evaluated with a sensitivity of 85.71%, a
      specificity of 86.67%, an accuracy of 86.19% and a Matthew's correlation
      coefficient (MCC) of 0.7238 for lysine as well as a sensitivity of 89.08%, a
      specificity of 94.07%, an accuracy of 91.56% and a MCC of 0.8323 for arginine in
      10-fold cross-validation test. It is shown through the analysis of the optimal
      feature subset that some upstream and downstream residues play important role in
      the methylation of arginine and lysine. Compared with other existing methods, the
      Methy_SVMIACO provides higher Acc, Sen and Spe, indicating that the current
      method may serve as a powerful complementary tool to other existing approaches in
      this area. The Methy_SVMIACO can be acquired freely on request from the authors.

PMID- 21889631
TI  - A three-dimensional hierarchical nanoporous PdCu alloy for enhanced
      electrocatalysis and biosensing.
AB  - Nanoporous copper (NPC) obtained by dealloying CuAl alloy is used as both three
      dimensional template and reducing agent for the fabrication of nanoporous PdCu
      alloy with hollow ligaments by a simple galvanic replacement reaction with
      H(2)PdCl(4) aqueous solution. Electron microscopy and X-ray diffraction
      characterizations demonstrate that after the replacement reaction, the ligaments
      become hollow tubular structure and the ligament shell is also comprised of small
      pores and nanoparticles with a typical size of ~4 nm (third order porosity). The
      as-prepared nanotubular mesoporous PdCu alloy (NM-PdCu) structure exhibits
      remarkably improved electrocatalytic activity towards the oxidation of formic
      acid and H(2)O(2) compared with nanoporous Pd (NP-Pd), and can be used for
      sensitive electrochemical sensing applications. After coupled with glucose
      oxidase (GOx), the enzyme modified NM-PdCu electrode can sensitively detect
      glucose over a wide linear range (0.5-20 mM).

PMID- 21889632
TI  - Pre-analytical method for NMR-based grape metabolic fingerprinting and
      chemometrics.
AB  - Although metabolomics aims at profiling all the metabolites in organisms, data
      quality is quite dependent on the pre-analytical methods employed. In order to
      evaluate current methods, different pre-analytical methods were compared and used
      for the metabolic profiling of grapevine as a model plant. Five grape cultivars
      from Portugal in combination with chemometrics were analyzed in this study. A
      common extraction method with deuterated water and methanol was found effective
      in the case of amino acids, organic acids, and sugars. For secondary metabolites
      like phenolics, solid phase extraction with C-18 cartridges showed good results.
      Principal component analysis, in combination with NMR spectroscopy, was applied
      and showed clear distinction among the cultivars. Primary metabolites such as
      choline, sucrose, and leucine were found discriminating for 'Alvarinho', while
      elevated levels of alanine, valine, and acetate were found in 'Arinto' (white
      varieties). Among the red cultivars, higher signals for citrate and GABA in
      'Touriga Nacional', succinate and fumarate in 'Aragones', and malate, ascorbate,
      fructose and glucose in 'Trincadeira', were observed. Based on the phenolic
      profile, 'Arinto' was found with higher levels of phenolics as compared to
      'Alvarinho'. 'Trincadeira' showed lowest phenolics content while higher levels of
      flavonoids and phenylpropanoids were found in 'Aragones' and 'Touriga Nacional',
      respectively. It is shown that the metabolite composition of the extract is
      highly affected by the extraction procedure and this consideration has to be
      taken in account for metabolomics studies.

PMID- 21889633
TI  - Optimized cleanup method for the determination of short chain polychlorinated n
      alkanes in sediments by high resolution gas chromatography/electron capture
      negative ion-low resolution mass spectrometry.
AB  - The performances of three adsorbents, i.e. silica gel, neutral and basic alumina,
      in the separation of short chain polychlorinated n-alkanes (sPCAs) from potential
      interfering substances such as polychlorinated biphenyls (PCBs) and
      organochlorine pesticides were evaluated. To increase the cleanup efficiency, a
      two-step cleanup method using silica gel column and subsequent basic alumina
      column was developed. All the PCB and organochlorine pesticides could be removed
      by this cleanup method. The very satisfying cleanup efficiency of sPCAs has been
      achieved and the recovery in the cleanup method reached 92.7%. The method
      detection limit (MDL) for sPCAs in sediments was determined to be 14 ng g(-1).
      Relative standard deviation (R.S.D.) of 5.3% was obtained for the mass fraction
      of sPCAs by analyzing four replicates of a spiked sediment sample. High
      resolution gas chromatography/electron capture negative ion-low resolution mass
      spectrometry (HRGC/ECNI-LRMS) was used for sPCAs quantification by monitoring [M
      HCl](-) ions. When applied to the sediment samples from the mouth of the Daliao
      River, the optimized cleanup method in conjunction with HRGC/ECNI-LRMS allowed
      for highly selective identifications for sPCAs. The sPCAs levels in sediment
      samples are reported to range from 53.6 ng g(-1) to 289.3 ng g(-1). C(10)- and
      C(11)-PCAs are the dominant residue in most of investigated sediment samples.

PMID- 21889634
TI  - Implications of partial tryptic digestion in organic-aqueous solvent systems for
      bottom-up proteome analysis.
AB  - For bottom-up MS, the digestion step is critical and is typically performed with
      trypsin. Solvent-assisted digestion in 80% acetonitrile has previously been shown
      to improve protein sequence coverage at shorter digestion times. This has been
      attributed to enhanced enzyme digestion efficiency in this solvent. However, our
      results demonstrate that tryptic digestion in 80% acetonitrile is less efficient
      than that of conventional (aqueous) digestion. This is a consequence of decreased
      enzyme activity beyond ~40% acetonitrile, increased enzyme autolysis and lower
      protein solubility in 80% acetonitrile. We observe multiple missed cleavages and
      reduced concentration of fully cleaved digestion products. Nonetheless we
      confirm, through room temperature solvent-assisted digestion, a consistent
      improvement in protein sequence coverage when analyzed by mass spectrometry.
      These results are explained through the increased number of unique digestion
      products available for detection. Thus, while solvent-assisted digestion has
      clear merits for proteome analysis, one should be aware of the inefficiency of
      protein digestion though this protocol, particularly with absolute protein
      quantitation experiments.

PMID- 21889635
TI  - Metabolomic approach for determination of key volatile compounds related to beef
      flavor in glutathione-Maillard reaction products.
AB  - The non-targeted analysis, combining gas chromatography coupled with time-of
      flight mass spectrometry (GC-TOF/MS) and sensory evaluation, was applied to
      investigate the relationship between volatile compounds and the sensory
      attributes of glutathione-Maillard reaction products (GSH-MRPs) prepared under
      different reaction conditions. Volatile compounds in GSH-MRPs correlating to the
      sensory attributes were determined using partial least-squares (PLS) regression.
      Volatile compounds such as 2-methylfuran-3-thiol, 3-sulfanylpentan-2-one, furan-2
      ylmethanethiol, 2-propylpyrazine, 1-furan-2-ylpropan-2-one, 1H-pyrrole, 2
      methylthiophene, and 2-(furan-2-ylmethyldisulfanylmethyl)furan could be
      identified as possible key contributors to the beef-related attributes of GSH
      MRPs. In this study, we demonstrated that the unbiased non-targeted analysis
      based on metabolomic approach allows the identification of key volatile compounds
      related to beef flavor in GSH-MRPs.

PMID- 21889636
TI  - Determination of amines based on their interaction with QDs: effect of the
      formation QD-assemblies.
AB  - Assemblies of closed nanoparticles have focused interest because they exhibit new
      optical and chemical properties. The use of a 1D covalent strategy for quantum
      dots-assemblies has been proposed in this work as novelty. It was studied the
      effect of use different dithiols, including aromatic and aliphatic dithiol
      compounds, on the formation of QDs-assemblies in order to establish the influence
      of the linker's structure on the geometry of the assemblies, and hence on their
      properties. As a second part of the work, the changes on analytical response to
      analytes thanks to the formation of QDs-assemblies when dithiols are added were
      studied for firs time. For this study, some biogenic amines were selected as
      target analytes. We observed an improvement of 2.7-4 times in the sensitivity,
      expressed as slope of the calibration graph, when the dithiols were added to the
      system obtaining QDs-assemblies.

PMID- 21889637
TI  - A carbohydrate modified fluoride ion sensor and its applications.
AB  - A new fluorescent probe for the detection of F(-) (TBA(+) and Na(+) salts) has
      been developed, which is based on a desilylation triggered chromogenic reaction
      in water. This probe exhibits excellent F(-) ion selectivity as well as
      significant color changes visible to the naked eye at the concentration of 1.5 mg
      L(-1), the WHO recommended level of F(-) ions in drinking water. This new
      carbohydrate modified probe can be used directly in aqueous medium without using
      organic co-solvents. Furthermore, the probe presents high sensitivity and
      selectivity for the imaging of F(-) ions in HepG2 cells.

PMID- 21889638
TI  - Molecularly imprinted polymers as optical sensing receptors: correlation between
      analytical signals and binding isotherms.
AB  - Despite the increasing number of usage of molecularly imprinted polymers (MIPs)
      in optical sensor application, the correlation between the analytical signals and
      the binding isotherms has yet to be fully understood. This work investigates the
      relationship between the signals generated from MIPs sensors to its respective
      binding affinity variables generated using binding isotherm models. Two different
      systems based on the imprinting of metal ion and organic compound have been
      selected for the study, which employed reflectance and fluorescence sensing
      schemes, respectively. Batch binding analysis using the standard binding isotherm
      models was employed to evaluate the affinity of the binding sites. Evaluation
      using the discrete bi-Langmuir isotherm model found both the MIPs studied have
      generally two classes of binding sites that was of low and high affinities, while
      the continuous Freundlich isotherm model has successfully generated a
      distribution of affinities within the investigated analytical window. When the
      MIPs were incorporated as sensing receptors, the changes in the analytical signal
      due to different analyte concentrations were found to have direct correlation
      with the binding isotherm variables. Further data analyses based on this
      observation have generated robust models representing the analytical performance
      of the optical sensors. The best constructed model describing the sensing trend
      for each of the sensor has been tested and demonstrated to give accurate
      prediction of concentration for a series of spiked analytes.

PMID- 21889639
TI  - Surface-enhanced Raman scattering detection of cholinesterase inhibitors.
AB  - A new sensitive surface-enhanced Raman scattering (SERS) assay for detection of
      cholinesterase inhibitors such as organophosphorous pesticides using silver
      colloidal nanoparticles was developed and optimized. Acetylcholinesterase (AChE)
      mediated the hydrolysis of acetylthiocholine to produce thiocholine, which
      interacted with the silver nanoparticles to give a specific SERS spectrum.
      Variation in enzyme activity due to inhibition was measured from changes in
      intensity of a characteristic peak (772 cm(-1)) of the SERS spectrum that was
      directly correlated with the concentration of produced thiocholine. The method
      was demonstrated for the detection of paraoxon as reference AChE inhibitor. Limit
      of detection of paraoxon for 5 min incubation at 25  degrees C was 1.8*10(-8) M.
      This assay can be utilized for the detection of trace amounts of any AChE
      inhibitor.

PMID- 21889640
TI  - Comparison of molecular imprinted particles prepared using precipitation
      polymerization in water and chloroform for fluorescent detection of
      nitroaromatics.
AB  - A comparative study was conducted to study the effects that two different
      polymerization solvents would have on the properties of imprinted polymer
      microparticles prepared using precipitation polymerization. Microparticles
      prepared in chloroform, which previous results indicated was the optimal solvent
      for molecular imprinting of nitroaromatic explosive compounds, were compared to
      water, which was hypothesized to decrease water swelling of the polymer and allow
      enhanced rebinding of aqueous template. The microparticles were characterized and
      were integrated into a fluorescence sensing mechanism for detection of
      nitroaromatic explosive compounds. The performance of the sensing mechanisms was
      compared to illustrate which polymerization solvent produced optimal imprinted
      polymer microparticles for detection of nitroaromatic molecules. Results
      indicated that the structures of microparticles synthesized in chloroform versus
      water varied greatly. Sensor performance studies showed that the microparticles
      prepared in chloroform had greater imprinting efficiency and higher template
      rebinding than those prepared in water. For detection of 2,4,6-trinitrotoluene,
      the chloroform-based fluorescent microparticles achieved a lower limit of
      detection of 0.1 MUM, as compared to 100 MUM for the water-based fluorescent
      microparticles. Detection limits for 2,4-dinitrotoluene, as well as time response
      studies, also demonstrated that the chloroform-based particles are more effective
      for detection of nitroaromatic compounds than water-based particles. These
      results illustrate that the enhanced chemical properties of using the
      experimentally determined optimal polymerization solvent overcome deformation of
      imprinted binding sites by water swelling and benefits of using the
      polymerization solvent for rebinding of the template.

PMID- 21889641
TI  - Anomalies in evaporative light scattering detection.
AB  - A two-dimensional (2-D) "heart-cutting" HPLC system was used to fractionate
      oligostyrenes into the respective diastereoisomers. For samples of known
      composition, the response of an ultraviolet (UV) absorbance detector followed the
      anticipated pattern. The response of an evaporative light-scattering (ELSD)
      detector on the other hand indicated quite different concentrations for the two
      diastereoisomers, relative to what was anticipated and what was indicated by the
      UV detector. Whereas approximately the same concentration was indicated by UV,
      ELSD in some cases indicated no detection of the later eluting isomer. The
      magnitude of the errors depended on both the molecular weight and the tacticity
      of the diastereomers. These anomalies appear to be an artifact of power transform
      functions imbedded within the firmware processor of the ELSD, invisible to the
      user.

PMID- 21889642
TI  - Weak affinity ligands selection using quartz crystal microbalance biosensor:
      multi-hydroxyl amine ligands for protein separation.
AB  - Multi-hydroxyl amines including tris(hydroxymethyl)aminomethane (Tris), serinol
      and ethanolamine were selected as weak affinity ligands using a rapid screening
      by quartz crystal microbalance (QCM) biosensor. Based on the specific recognition
      between the ligands and two proteins, lysozyme (LZM) and cytochrome c (Cyt c), a
      weak affinity chromatography method was developed for specific separation of the
      two proteins. The frontal analysis results showed that the apparent dissociation
      constants (K(D)) of ligand-protein complexes were all in the order of weak
      affinity (10(-4) M). By weak affinity columns modified with the three multi
      hydroxyl amines individually, LZM and Cyt c were baseline separated as retarded
      peaks from non-specific protein and each other in a single cycle of loading and
      eluting. Moreover, the Tris-modified column typically showed the satisfactory
      repeatability and stability as a new type of weak affinity columns. The present
      strategy composed of QCM selecting and affinity chromatography separating was
      promising to extend the variety of weak affinity ligands and develop inexpensive
      specific affinity methods for separation and purification of multiple proteins on
      one single column.

PMID- 21889643
TI  - One-pot labeling-based capillary zone electrophoresis for separation of amino
      acid mixture and assay of biofluids.
AB  - A fast, simple and cost-effective one-pot labeling strategy coupled with
      capillary zone electrophoresis was developed for the complete separation of amino
      acid mixture. The strategy includes two steps of reactions: Cyanuric chloride was
      made to react first with 7-amino-1,3-naphthalenedisulfonic acid monopotassium
      salt at 0  degrees C for 10 min, and then with amino acids at 55  degrees C for 6
      min. The resulted products, after diluted with water, were injected into
      capillary zone electrophoresis system for separation. Using a running buffer of
      20 mM sodium tetraborate decahydrate at pH 10.1, nineteen amino acids were
      efficiently separated in 25 min, with relative standard deviation of 0.36-1.6%
      and 0.96-2.1% (within and between days, respectively) for migration time and
      0.030-1.6% and 0.22-2.4% (within and between days, respectively) for peak area.
      The proposed method has been successfully applied to the determination of free
      amino acids in biofluids, including human serum, urine, and saliva. The linearity
      of quantification was over two orders of magnitude for most amino acids, with a
      correlation coefficient larger than 0.999. The average recovery, determined by
      spiking a known amount of amino acid standards into real samples, was in a range
      from 91.6% to 105.9%. This method can be a noninvasive means since it could
      directly assay the urine and saliva samples.

PMID- 21889644
TI  - Memories and the human spirit.

PMID- 21889645
TI  - Reflections on a defining moment.

PMID- 21889646
TI  - Ten years later: reflections of 9/11.

PMID- 21889647
TI  - Ten years later: reflections of 9/11.

PMID- 21889648
TI  - Ten years later: reflections of 9/11.

PMID- 21889649
TI  - Ten years later: reflections of 9/11.

PMID- 21889650
TI  - Catastrophic progression of preterm delivery caused by 2009 H1N1 influenza
      infection.

PMID- 21889651
TI  - Emergency department policies and procedures for treatment of patients abusing
      methamphetamine.

PMID- 21889652
TI  - Theory development for situational awareness in multi-casualty incidents.
AB  - INTRODUCTION: Nurses and other field-level providers will be increasingly called
      on to respond to both natural and manmade situations that involve multiple
      casualties. Situational Awareness (SA) is necessary for managing these
      complicated incidents. The purpose of the study was to create new knowledge by
      discovering the process of SA in multi-casualty incidents (MCI) and develop
      substantive theory with regard to field-level SA for use by emergency response
      nurses and other providers. METHODS: A qualitative, grounded theory approach was
      used to develop the first substantive theory of SA for MCI. The sample included
      15 emergency response providers from the Southeastern United States. One pilot
      interview was conducted to trial and refine the semi-structured interview
      questions. Following Institutional Review Board approval, data collection and
      analysis occurred from September 2008 through January 2009. The grounded theory
      methods of Corbin and Strauss (2008) and Charmaz (2006) informed this study.
      Transcribed participant interviews constituted the bulk of the data with
      additional data provided by field notes and extensive memos. Multiple levels of
      coding, theoretical sampling, and theoretical sensitivity were used to develop
      and relate concepts resulting in emerging theory. Multiple methods were used for
      maintaining the rigor of the study. RESULTS: The process of SA in MCI involves
      emergency responders establishing and maintaining control of dynamic,
      contextually-based situations. Against the backdrop of experience and other
      preparatory interval actions, responders handle various types of information and
      manage resources, roles, relationships and human emotion. The goal is to provide
      an environment of relative safety in which patient care is provided. SA in MCI is
      an on-going and iterative process with each piece of information informing new
      actions. Analysis culminated in the development of the Busby Theory of
      Situational Awareness in Multi-casualty Incidents. CONCLUSION: SA in MCI is a
      growing need at local, national and international levels. The newly developed
      theory provides a useful model for appreciating SA in the context of MCI thereby
      improving practice and providing a tool for education. The theory also provides a
      catalyst for further research refining and testing of the theory and for studying
      larger-scale incidents.

PMID- 21889653
TI  - Responding to mental health emergencies: implementation of an innovative
      telehealth service in rural and remote new South Wales, Australia.
AB  - INTRODUCTION: Mental health is a national priority in Australia, and the need is
      greatest where access to specialist care is poorest, in the rural and remote
      regions of the nation. The Mental Health Emergency Care-Rural Access Project
      (MHEC) was developed to provide 24-hour access to mental health specialists in
      rural and remote New South Wales using video conferencing equipment. METHOD: An
      evaluation of the service activity of MHEC using a concurrent mixed methods
      approach. RESULTS: Use of the service increased from a low base to around 60
      video assessments per month at the end of the study period. Use of video
      assessments was greatest in the remote zone (30.7 video assessments/10,000
      population/year). The number of people referred to a mental health inpatient unit
      declined (50 fewer patients, representing a decrease from 73% to 52% of all
      admissions between 2008 and 2009). Both patients and providers found the service
      helpful. Most patients (81%) stated that they would recommend or use the service
      again. DISCUSSION: This service is well positioned to have an increasing effect
      on emergency nursing and patient outcomes, as well as potentially on
      transportations. Continued use of MHEC suggests that video conference technology
      is acceptable and offers responsive specialist emergency mental health care to
      rural and remote communities.

PMID- 21889654
TI  - Treatment of hemophilia with inhibitors: an advance in options for pediatric
      patients.

PMID- 21889655
TI  - Nursing process and critical thinking linked to disaster preparedness.

PMID- 21889656
TI  - Responding to a multiple-casualty incident: room for improvement.

PMID- 21889657
TI  - A 57-year-old woman with atypical chest pain.

PMID- 21889658
TI  - Three people, three different complaints, three stories, one thing in common.

PMID- 21889660
TI  - Myocardial revascularization by percutaneous coronary intervention: past,
      present, and the future.
AB  - Percutaneous coronary revascularization was introduced over 30 years ago by Dr
      Andreas Gruntzig. This event catapulted adult invasive cardiology from a
      diagnostic entity to a therapeutic modality, which has since become the most
      frequently performed coronary revascularization procedure worldwide. This success
      has been built on several key concepts-problem identification, targeted
      solutions, applied technology, populations-based testing, postmarket
      surveillance, and education. These concepts will continue to be of paramount
      importance as novel percutaneous innovations and strategies are brought to bear
      on an increasingly broader group of patients with cardiovascular disease. In this
      review, we trace the history, review current practices, and also provide insight
      into future potential innovations, as it pertains to percutaneous coronary
      revascularization.

PMID- 21889661
TI  - Improving cataract surgery refractive outcomes.

PMID- 21889662
TI  - Orbital inflammation and lyme disease.

PMID- 21889663
TI  - Golimumab for uveitis.

PMID- 21889664
TI  - Beta-blockade affects simulator scores.

PMID- 21889665
TI  - Surgery for floaters.

PMID- 21889666
TI  - Blue-blocking IOLs.

PMID- 21889668
TI  - Blue-blocking IOLs.

PMID- 21889670
TI  - Repeat endothelial keratoplasty.

PMID- 21889672
TI  - Pediatric lamellar keratoplasty.

PMID- 21889674
TI  - Preface.

PMID- 21889675
TI  - Medically unexplained symptoms: a treacherous foundation for somatoform
      disorders?

PMID- 21889676
TI  - The somatoform disorders: 6 characters in search of an author.

PMID- 21889678
TI  - The relationship between somatic symptoms, health anxiety, and outcome in medical
      out-patients.

PMID- 21889677
TI  - Health care utilization and poor reassurance: potential predictors of somatoform
      disorders.

PMID- 21889679
TI  - Relevance of cognitive and behavioral factors in medically unexplained syndromes
      and somatoform disorders.

PMID- 21889680
TI  - Does psychological stress cause chronic pain?

PMID- 21889681
TI  - Can neural imaging explain pain?

PMID- 21889683
TI  - Simulated illness: the factitious disorders and malingering.

PMID- 21889684
TI  - Somatoform disorders in children and adolescents.

PMID- 21889682
TI  - Inflammation at the intersection of behavior and somatic symptoms.

PMID- 21889685
TI  - Somatization in older people.

PMID- 21889686
TI  - Functional somatic syndromes and somatoform disorders in special psychosomatic
      units: organizational aspects and evidence-based treatment.

PMID- 21889687
TI  - Teaching trainees about the practice of consultation-liaison psychiatry in the
      general hospital.

PMID- 21889688
TI  - Preface: Surgical complications.

PMID- 21889689
TI  - Metabolic complications of endocrine surgery in companion animals.
AB  - Metabolic complications of endocrine surgery occur commonly and precautions
      should be taken to avoid potentially life-threatening situations and to lessen
      expense associated with a more extended hospital stay. Common complications of
      endocrine surgery as well as prevention strategies will be reviewed for
      pancreatic, parathyroid, and adrenal surgery.

PMID- 21889690
TI  - Complications of upper urinary tract surgery in companion animals.
AB  - Due to the negative effects of urine on wound healing, the high rate of
      complications associated with surgical incisions in the ureter and a desire to
      avoid large open approaches to the abdomen, there is a strong trend in human
      medicine toward the use of endoscopic methods in the treatment of upper urinary
      tract disease. However, the small size of urogenital structures in companion
      animals has prevented the widespread application of endoscopy of the upper
      urinary tract and surgery continues to be the mainstay of treatment. Through
      careful decision making, veterinary surgeons now use microsurgical technique and
      interventional radiology to provide a high success rate. The current review will
      discuss complications pertaining to surgery of the kidney and ureter in companion
      animals, using experimental and clinical data to guide the detection and
      avoidance of these complications.

PMID- 21889691
TI  - Complications of lower urinary tract surgery in small animals.
AB  - Surgical procedures of the lower urinary tract are commonly performed in small
      animal practice. Cystotomy for removal of uroliths and urethrostomy diverting
      urine outflow due to urethral obstruction are the most commonly performed
      surgical procedures of the bladder and urethra respectively. Surgical procedures
      of the lower urinary tract are typically associated with few complications,
      including leakage of urine, loss of luminal diameter (stricture or stenosis),
      urine outflow obstruction, tissue devitalization, denervation, urinary
      incontinence, urinary tract infection, and death. Complications can result from
      inappropriate or inadequate diagnosis, localization, and surgical planning;
      failure to respect regional anatomy, and other causes.

PMID- 21889692
TI  - Complications of gastrointestinal surgery in companion animals.
AB  - The small animal surgeon creates wounds in the gastrointestinal (GI) tract for
      biopsy, for foreign body or neoplasm removal, or to relieve obstruction. Unlike a
      skin wound, dehiscence of a wound of the GI tract often leads to generalized
      bacterial peritonitis and potentially death. Technical failures and factors that
      negatively affect GI healing are of great clinical significance. Surgery of the
      GI tract must be considered clean-contaminated at best; as one progresses
      aborally down the GI tract, the bacterial population increases. Intraoperative
      spillage, wound dehiscence, or perforations that occur in the lower small
      intestine or colon tend to be associated with a relatively higher mortality rate.

PMID- 21889693
TI  - Complications of hepatic surgery in companion animals.
AB  - The most common hepatic procedures performed in companion animals are liver
      biopsies and partial or complete liver lobectomies. Although these procedures are
      relatively simple to perform in healthy animals, surgery in clinical patients
      with liver disease is often complicated by the presence of significant systemic
      illness or by the technical challenges associated with removing massive hepatic
      tumors. An in-depth understanding of the possible complications that can occur
      with hepatic surgery helps to provide the best possible outcome for the patient
      by allowing the surgeon to not only take precautions to try to prevent
      complications but allows one to monitor for them postoperatively and treat them
      early if noted.

PMID- 21889694
TI  - Complications of the extrahepatic biliary surgery in companion animals.
AB  - Surgery of the biliary tract is demanding and is associated with several
      potentially life-threatening complications. Veterinarians face challenges in
      obtaining accurate diagnosis of biliary disease, surgical decision-making,
      surgical hemostasis and bile peritonitis. Intensive perioperative monitoring is
      required to achieve early recognition of common postoperative complications.
      Proper treatment and ideally, avoidance of surgical complications can be achieved
      by gaining a clear understanding physiology, anatomy, and the indications for
      hepatobiliary surgery.

PMID- 21889695
TI  - Complications of upper airway surgery in companion animals.
AB  - Surgery of the upper airway is performed in dogs for the correction of
      brachycephalic airway syndrome and laryngeal paralysis and for temporary or
      permanent tracheostomy. Although technically simple to perform, upper airway
      surgeries can lead to the development of significant postoperative complications.
      This article reviews complications associated with common surgical conditions of
      the upper airway. It involves a discussion of brachycephalic airway syndrome and
      associated respiratory and gastrointestinal complications. It also covers
      laryngeal paralysis with a focus on unilateral arytenoid lateralization and the
      complication of aspiration pneumonia. The condition of acquired laryngeal
      webbing/stenosis and potential treatment options is also discussed. Finally,
      tracheostomies and associated complications in dogs and cats are reviewed.

PMID- 21889696
TI  - Management of complications associated with total ear canal ablation and bulla
      osteotomy in dogs and cats.
AB  - Total ear canal ablation combined with bulla osteotomy is a salvage procedure
      recommended primarily for end-stage inflammatory ear canal disease but also for
      neoplasia and severe traumatic injuries. Due to the complexity of the procedure
      and the poor exposure associated with the surgical approach, there is significant
      risk for a variety of complications. This review discusses intraoperative, early
      postoperative, and late postoperative complications reported in large
      retrospective studies, the causes for these complications, and recommendations
      about how to prevent them.

PMID- 21889697
TI  - Complications of reconstructive surgery in companion animals.
AB  - Factors that affect wound healing include the general health of the patient,
      nutritional status, and wound factors. Treatments such as corticosteroids,
      chemotherapy, or radiation are also common causes of delayed healing. Multimodal
      cancer treatment has become more common and the veterinary surgeon may be
      required to perform reconstructive procedures on an animal that has received or
      will receive chemotherapy and/or radiation treatments. Complications of
      reconstructive cutaneous procedures include seroma, hematoma formation,
      infection, wound dehiscence, distal tip necrosis of skin flaps, paresthesia, and
      free skin graft failure. Procedures such as maxillectomy or hemipelvectomy also
      have complications. Knowledge of common complications can facilitate client
      education and even allow the surgeon to avoid these complications.

PMID- 21889698
TI  - Complications of minimally invasive surgery in companion animals.
AB  - Minimally invasive surgery (MIS) has become increasingly popular in recent years
      for diagnosis and treatment of an ever-expanding list of disease processes in
      small animal patients. Reports in the veterinary literature have documented a
      large number of MIS alternatives to traditional open surgery albeit mostly in
      small cohorts of patients. Advantages of MIS have been documented by many
      investigators and include significant decreases in postoperative pain, length of
      hospital stay, and analgesic requirements, as well as other types of morbidity,
      with some procedures now being performed on an outpatient basis. However, MIS
      procedures are not without surgical morbidity and in some cases may be associated
      with higher levels or different types of complications compared to open surgery.

PMID- 21889699
TI  - Complications of ovariohysterectomy and orchiectomy in companion animals.
AB  - Complications following elective spay or neuter procedures are particularly
      feared by new graduates. However, even the most experienced surgeons may
      encounter surgical or postoperative complications. At best, complications
      associated with elective procedures can harm the doctor-client relationship. At
      worst, these can present legal and financial problems. Veterinary surgeons should
      be aware of the potential complications associated with elective sterilization,
      these should be communicated to the client, and there should be a clear plan for
      action when a complication occurs. This article reviews the reported
      complications encountered in elective sterilization surgery in companion animals,
      with a special focus on early detection and prevention.

PMID- 21889700
TI  - Surgical site infections in small animal surgery.
AB  - Surgical site infections (SSIs) are a significant source of morbidity, mortality,
      and cost associated with small animal surgery. The most well-established
      strategies to reduce the impact of SSI are preventive, focusing on bolstering
      host immunity while decreasing wound contamination during surgery. When SSI is
      identified, the use of consistent definitions and culture-based therapy help to
      facilitate surveillance and appropriate management. Debridement and open wound
      management of infected wounds are important for successful treatment.

PMID- 21889701
TI  - Updated Society for Vascular Surgery guidelines for management of extracranial
      carotid disease.
AB  - Management of carotid bifurcation stenosis is a cornerstone of stroke prevention
      and has been the subject of extensive clinical investigation, including multiple
      controlled randomized trials. The appropriate treatment of patients with carotid
      bifurcation disease is of major interest to the community of vascular surgeons.
      In 2008, the Society for Vascular Surgery published guidelines for treatment of
      carotid artery disease. At the time, only one randomized trial, comparing carotid
      endarterectomy (CEA) and carotid stenting (CAS), had been published. Since that
      publication, four major randomized trials comparing CEA and CAS have been
      published, and the role of medical management has been re-emphasized. The current
      publication updates and expands the 2008 guidelines with specific emphasis on six
      areas: imaging in identification and characterization of carotid stenosis,
      medical therapy (as stand-alone management and also in conjunction with
      intervention in patients with carotid bifurcation stenosis), risk stratification
      to select patients for appropriate interventional management (CEA or CAS),
      technical standards for performing CEA and CAS, the relative roles of CEA and
      CAS, and management of unusual conditions associated with extracranial carotid
      pathology. Recommendations are made using the GRADE (Grades of Recommendation
      Assessment, Development and Evaluation) system, as has been done with other
      Society for Vascular Surgery guideline documents.[corrected] The perioperative
      risk of stroke and death in asymptomatic patients must be <3% to ensure benefit
      for the patient. CAS should be reserved for symptomatic patients with stenosis of
      50% to 99% at high risk for CEA for anatomic or medical reasons. CAS is not
      recommended for asymptomatic patients at this time. Asymptomatic patients at high
      risk for intervention or with <3 years life expectancy should be considered for
      medical management as the first-line therapy.

PMID- 21889702
TI  - One year outcomes of the United States regulatory trial of the Endurant Stent
      Graft System.
AB  - OBJECTIVE: To report the 1-year outcomes of the United States (US) regulatory
      trial of the Endurant Stent Graft System (Medtronic Vascular), a new device for
      the treatment of abdominal aortic aneurysms (AAA). METHODS: This was a
      prospective, single arm, multicenter trial conducted at 26 sites in the US. From
      April 2008 to May 2009, 150 patients with AAA were treated with the Endurant
      bifurcated stent graft. The main inclusion criteria were an AAA diameter >5 cm,
      proximal neck length >= 10 mm, bilateral iliac fixation length >= 15 mm, and a
      neck angulation of <= 60 degrees. A clinical events committee (CEC) adjudicated
      all adverse events except blood loss, and a core laboratory reviewed all imaging.
      The primary safety endpoint was freedom from major adverse events at 30 days, and
      the primary effectiveness endpoint was successful aneurysm treatment at 12
      months. RESULTS: One hundred forty-nine patients (99.3%) had a successful stent
      graft implant, 83.3% under general anesthesia. One failure was due to inability
      to cannulate the contralateral gate. One patient developed a neck rupture during
      the procedure, but was still treated successfully. Patients were predominantly
      male (91.3%), elderly (mean age, 73.1 years) with significant comorbidities. Mean
      estimated blood loss was 185 mL (range, 0-1450 mL), with blood transfusion
      required in one patient. Average hospital stay was 2.1 days. At 1 month, the
      major adverse events rate was only 4% with no operative mortality. Serious
      adverse events were recorded in 43 of 150 (28.7%) patients. Cardiac (8.7%), fever
      (6%), urological (4.7%), pulmonary (4%), and vascular events (4%) were the most
      frequent. Through 12 months of follow up, there were no migrations, ruptures, or
      conversions. No type I or III endoleaks were identified during the first year.
      Fifteen of 129 patients (11.6%) had endoleaks at 6 months and 13 of 130 (10%) at
      1 year, all type II except for one indeterminate endoleak. One Type II endoleak
      proved to be a Type IB on later angiography. Ten aneurysm related reinterventions
      were performed during the first year of follow up, mostly for limb thrombosis or
      stenosis (5) or for type II endoleak (2). Four of the procedures were
      endovascular. Aneurysm sac diameter decreased >5 mm at 1 year in 47% of patients
      and remained stable in 53%. No sac showed an increase of >5 mm. None of seven
      late deaths (range, 90-458 days post-implant) was adjudicated to be aneurysm
      related. CONCLUSION: Early results of the Endurant pivotal trial are quite
      encouraging and suggest a safe and effective new device for the treatment of
      abdominal aortic aneurysms.

PMID- 21889703
TI  - Prevalence and clinical significance of stent fracture and deformation following
      carotid artery stenting.
AB  - OBJECTIVE: Carotid artery stenting (CAS) is a developing intervention for carotid
      artery stenosis, and long-term outcomes remain unclear. We examined the
      prevalence and clinical significance of carotid stent fractures or deformations
      following CAS. METHODS: Two hundred thirty-one CAS performed in 219 patients at
      one academic institution between August 2000 and March 2009 were reviewed. One
      hundred sixteen stents (57 closed cell, 59 open cell) were evaluated with
      multiplanar plain films of the neck to assess for stent fracture or deformation.
      Stent fracture was identified by wire strut disruption. Deformation was defined
      as an increase in stent-cell area from stent strut distortion. Study endpoints
      included rate of stent fracture or deformation determined using Kaplan-Meier and
      life table analysis. Factors associated with stent fracture or deformation were
      identified by Cox regression. Effect of stent fracture or deformation on
      recurrent carotid artery stenosis >70% requiring reintervention and postoperative
      stroke was studied. RESULTS: There were five stent fractures (4%) and 27 deformed
      stents (23%). Rate of stent fracture or deformation was 15% at 2 years and 50% at
      4 years. Deformations were significantly more common in open cell stents than in
      closed cell stents (58% vs 5% at 4 years, P < .00005). Presence of calcified
      plaque on plain film was significantly associated with increased rate of stent
      fracture or deformation (P = .0006). At median follow-up of 25 months, restenosis
      requiring treatment occurred in four (5%) and late stroke in one (1%). Neither
      stent fracture nor deformation was associated with late stroke or reintervention.
      CONCLUSIONS: Stent fracture and deformation is not uncommon following CAS and is
      associated with the presence of heavy calcification. Whether a carotid stent
      fractures or deforms correlates with stent design. Larger studies are necessary
      to determine the possible clinical significance of carotid stent fracture and
      deformation.

PMID- 21889705
TI  - Updated Society for Vascular Surgery guidelines for management of extracranial
      carotid disease: executive summary.
AB  - In 2008, the Society for Vascular Surgery published guidelines for the treatment
      of carotid bifurcation stenosis. Since that time, a number of prospective
      randomized trials have been completed and have shed additional light on the best
      treatment of extracranial carotid disease. This has prompted the Society for
      Vascular Surgery to form a committee to update and expand guidelines in this
      area. The review was done using the GRADE methodology.[corrected] The
      perioperative risk of stroke and death in asymptomatic patients must be below 3%
      to ensure benefit for the patient. Carotid artery stenting (CAS) should be
      reserved for symptomatic patients with stenosis 50% to 99% at high risk for CEA
      for anatomic or medical reasons. CAS is not recommended for asymptomatic patients
      at this time. Asymptomatic patients at high risk for intervention or with <3
      years life expectancy should be considered for medical management as first line
      therapy. In this Executive Summary, we only outline the specifics of the
      recommendations made in the six areas evaluated. The full text of these
      guidelines can be found on the on-line version of the Journal of Vascular Surgery
      at http://journals.elsevierhealth.com/periodicals/ymva.

PMID- 21889706
TI  - Ethics of re-hearsing procedures on a corpse.
AB  - You are the attending surgeon of a homeless pedestrian who sustained multiple
      injuries when struck by a car. He died soon after being brought to the emergency
      department. It is late in the evening. A first-year resident and a medical
      student have been helping with the failed attempt at resuscitation. The emergency
      department is empty, except for your case. A central line kit lies on the bed,
      opened but not used. The junior resident asks your permission for herself and the
      student to practice the technique of subclavian cauterization and tracheal
      intubation on the fresh cadaver to get a "feel" for the procedures. There is no
      medical simulation for these procedures at your medical center. The best ethical
      response is: A. Tell them to go ahead and practice. B. They can only practice
      intubation because it leaves no external wounds. C. You should supervise them
      yourself to assure educational benefit. D. They should wait until you get
      permission from the medical examiner. E. The present case is not appropriate for
      educational purposes.

PMID- 21889707
TI  - ViPS technique as a novel concept for a sutureless vascular anastomosis.
AB  - OBJECTIVE: To describe a novel technique (Viabhan Padova Sutureless [ViPS]) that
      connects a vascular prosthetic graft to a target artery in a sutureless fashion.
      METHODS: The patient was a 74-year-old male with complete superficial femoral
      artery (FA) occlusion and reconstitution of a circumferentially calcified above
      knee popliteal artery (ANPA). The proximal end of a surgeon-modified 7-mm Viabahn
      endoprosthesis was sutured to a 7-mm polytetrafluoroethylene graft (PTFEg). After
      surgical exposure, the ANPA was transected, and the undeployed distal portion of
      the Viabahn was inserted, supported by a stiff guidewire. The distal portion of
      the Viabahn graft was then deployed and ballooned with optimal apposition.
      Finally, the proximal end of the PTFEg was sutured to the common FA. RESULTS:
      Operative time was 60 minutes. Completion angiogram and the computed tomography
      angiogram at 6 months demonstrated a patent graft. CONCLUSION: The ViPS technique
      provides an alternative for bypass creation when challenging arterial anastomoses
      are required.

PMID- 21889710
TI  - Regarding "Optimal statin type and dosage for vascular patients".

PMID- 21889708
TI  - Thrombolysis for acute ischemic stroke.
AB  - Thrombolysis with intravenous alteplase is the primary therapy for acute ischemic
      stroke, and is approved in most countries. Early administration improves
      functional outcome though benefit and risk depend on the time elapsed between
      stroke onset and initiation of treatment. Randomized controlled trials
      demonstrated benefit from intravenous thrombolysis when initiated up to 4.5 hours
      after symptom onset, and pooled analysis of all trials indicates that the sooner
      that alteplase is given, the greater is the benefit. Treatment carries a risk of
      bleeding, with symptomatic intracranial hemorrhage (SICH) of around 3%.
      Initiating treatment after 4.5 hours increases mortality and reverses the risk
      benefit balance. Baseline stroke severity, age, diabetes and concomitant stroke
      are associated with poorer outcome from acute stroke; but secondary analyses and
      controlled registry data suggest that intravenous alteplase remains effective in
      most subgroups. Intra-arterial thrombolysis has a less extensive evidence base
      and is mostly unapproved for acute stroke. Access to thrombolysis remains patchy
      and involves unacceptable delays: greater awareness of the benefits and time
      dependency are crucial.

PMID- 21889712
TI  - Hormones and cancer: breast and prostate.

PMID- 21889713
TI  - Endocrinology and Metabolism Clinics of North America. Hormones and cancer:
      breast and prostate. Preface.

PMID- 21889714
TI  - The pivotal role of insulin-like growth factor I in normal mammary development.
AB  - Mammary development begins in puberty in response to an estrogen (E(2)) surge.
      E(2) does not act alone. It relies on pituitary growth hormone (GH) to induce
      insulin-like growth factor I (IGF-I) production in the mammary stromal
      compartment. In turn, IGF-I permits E(2) (and progesterone) action. During
      puberty, E(2) and IGF-I synergize for ductal morphogenesis. During pregnancy,
      progesterone joins IGF-I and E(2) to stimulate secretory differentiation
      necessary to produce milk. Prolactin stimulates milk production, while
      transforming growth factor-beta inhibits proliferation. The orchestrated action
      of hormones, growth factors, and receptors necessary for mammary development and
      function are also critical in breast cancer.

PMID- 21889715
TI  - Estrogen carcinogenesis in breast cancer.
AB  - Many studies have reported a correlation between elevated estrogen blood levels
      and breast cancer and this observation has raised controversy concerning the long
      term use of hormonal replacement therapy. This review will not address further
      this controversial topic; but rather, this review focuses on the role of estrogen
      signaling in first, the normal development of the breast and second, how
      alterations of this signaling pathway contribute to breast cancer.

PMID- 21889716
TI  - Hormonal mechanisms underlying the relationship between obesity and breast
      cancer.
AB  - Given the worldwide epidemic of obesity, it is inevitably an increasingly common
      comorbidity for women who develop breast cancer; therefore, it is critical to
      understand its impact on this disease. This review focuses on the influence of
      obesity on breast cancer development and progression and describes the hormonal
      factors that may underlie the observations, with particular emphasis on the roles
      of estrogen, insulin/insulin-like growth factor axis, and adipokines.

PMID- 21889718
TI  - Hormonal modulation in the treatment of breast cancer.
AB  - This article explores the history of endocrine therapy for the treatment of
      breast cancer, the clinical evidence behind the current standards of care, and
      controversies that may change these standards in the future.

PMID- 21889717
TI  - Postmenopausal hormone therapy and breast cancer risk: current status and
      unanswered questions.
AB  - Many women take hormone therapy (HT) for menopausal symptom relief. Studies have
      tried to clarify whether various factors can modify the risk of HT, such as the
      age at initiation, dose, duration, or type of HT, or characteristics of the
      individual, such as family history or body mass index. The relative risks of
      breast cancer associated with HT across various subgroups of women should be
      considered similar, but absolute risks can vary significantly among women and
      this may inform individual decision making. For breast cancer survivors, systemic
      HT should be discouraged.

PMID- 21889719
TI  - Androgens and breast cancer in men and women.
AB  - Abundant clinical evidence suggests that androgens normally inhibit mammary
      epithelial proliferation and breast growth. Clinical and nonhuman primate studies
      support the notion that androgens inhibit mammary proliferation and, thus, may
      protect from breast cancer. On the other hand, administration of conventional
      estrogen treatment suppresses endogenous androgens and may, thus, enhance
      estrogenic breast stimulation and possibly breast cancer risk. Addition of
      testosterone to the usual hormone therapy regimen may diminish the
      estrogen/progestin increase in breast cancer risk, but the impact of this
      combined use on mammary gland homeostasis still needs evaluation.

PMID- 21889720
TI  - Management of bone disease in patients undergoing hormonal therapy for breast
      cancer.
AB  - Estrogen deficiency at menopause is associated with increased risk of bone loss
      and osteoporosis. Aromatase inhibitors (AIs) are increasingly being used for the
      treatment of postmenopausal hormone-sensitive breast cancer because of better
      disease-free survival compared with tamoxifen seen in clinical trials with AIs.
      This article reviews the effect of endocrine therapies of breast cancer on bone
      and the management of bone disease with these endocrine therapies. The effect of
      these therapies on bone mineral density and bone turnover along with possible
      interventions is discussed. AIs are also associated with skeletal-related events,
      which are not discussed.

PMID- 21889721
TI  - Overview of prostate anatomy, histology, and pathology.
AB  - The human prostate is heterogeneous with regard to its embryologic origin. The
      two most prevalent diseases of aging males, benign prostatic hyperplasia and
      prostate cancer (PCa), arise from different zones within the prostate. The
      biology of PCa is also heterogeneous and even within a single individual there
      often exist prostate cancers with varying potential to progress and metastasize.
      Through careful study of the histology and molecular signatures of both the human
      and mouse-modeled disease, treatment decisions can be tailored to individual
      cases so as to optimize efficacy and minimize side effects from therapy.

PMID- 21889722
TI  - The critical role of androgens in prostate development.
AB  - Androgens are involved in every aspect of prostate development, growth, and
      function from early in male embryogenesis to prostatic hyperplasia in aging men
      and dogs. Likewise, androgen deprivation at any phase of life causes a decrease
      in prostate cell number and DNA content. The process by which the circulating
      androgen testosterone is converted to dihydrotestosterone in the tissue and
      dihydrotestosterone in turn gains access to the nucleus where it regulates gene
      expression, largely via interaction with a receptor protein, is understood, but
      the downstream control mechanisms by which hormonal signals are translated into
      differentiation, growth, and function are being unraveled.

PMID- 21889724
TI  - The timing and extent of androgen deprivation therapy for prostate cancer:
      weighing the clinical evidence.
AB  - Androgen deprivation therapy (ADT) is an effective means of palliating symptoms
      of prostate cancer but is associated with significant toxicities that increase
      with treatment duration. Primary ADT in men with localized disease provides no
      survival advantage. Neoadjuvant ADT, when combined with external beam radiation,
      improves survival for men with locally advanced disease. Immediate adjuvant
      androgen deprivation does not seem to benefit most men undergoing radical
      prostatectomy. No evidence supports combined androgen blockade or monotherapy
      with nonsteroidal antiandrogens for locally advanced prostate cancer. ADT with
      orchiectomy or gonadotropin-releasing hormone agonists or antagonists is standard
      care for men with metastatic prostate cancer.

PMID- 21889726
TI  - Androgens and prostate cancer bone metastases: effects on both the seed and the
      soil.
AB  - Androgens are essential for normal prostate development and are necessary, but
      not sufficient, for the development of prostate cancer (PCa). Androgen
      deprivation therapy has long been the mainstay of treatment for PCa bone
      metastases, providing palliation of symptoms in the majority of patients,
      followed by relapse and progression. The majority of published preclinical
      studies demonstrate a stimulatory effect of androgens and androgen receptor
      signaling on the multistep process of PCa bone metastases, including androgenic
      promotion of local PCa growth, angiogenesis, invasion, bone targeting,
      stimulation of PCa growth factors that enhance osteoclastogenesis, and
      enhancement of Wnt signaling in osteoblasts.

PMID- 21889727
TI  - Management of side effects of androgen deprivation therapy.
AB  - Androgen deprivation therapy (ADT) is a major component of the contemporary
      management of prostate cancer. ADT's use is increasing rapidly. The side effects
      of this therapy include loss of bone mass and fractures, increase in fat mass,
      and worsening of insulin resistance, the metabolic syndrome, diabetes and
      cardiovascular risk, and anemia and loss of muscle. Neuropsychological and sexual
      symptoms are common. The impact of these side effects is often overlooked or
      underestimated in decisions about prostate cancer therapy. This review surveys
      the data relating to the side effects of ADT and provides recommendations
      regarding their minimization and management.

PMID- 21889728
TI  - [Open letter to the members of the French Hand Surgery Society].

PMID- 21889725
TI  - New hormonal therapies for castration-resistant prostate cancer.
AB  - Continued activation of the androgen receptor (AR) axis despite castration
      remains a critical force in the development of castration-resistant prostate
      cancer (CRPC). Therapeutic strategies designed to more effectively ablate tumoral
      androgen activity are required to improve clinical efficacy and prevent disease
      progression. Tumor-based alterations in expression and activity of the AR and in
      steroidogenic pathways mediating ligand generation facilitate the development of
      CRPC. This article reviews AR and ligand-dependent mechanisms underlying CRPC
      progression and the status of novel hormonal therapies targeting the AR axis that
      are currently in clinical and preclinical development.

PMID- 21889729
TI  - Reprint of: Theoretical and experimental basis of slow freezing.
AB  - In human IVF, cryopreservation of oocytes has become an alternative to embryo
      storage. It has also shown enormous potential for oocyte donation, fertility
      preservation and animal biotechnology. Mouse oocytes have represented the
      elective model to develop oocyte cryopreservation in the human and over several
      decades their use has made possible the development of theoretical and empirical
      approaches. Progress in vitrification has overshadowed slow freezing to such an
      extent that it has been suggested that vitrification could soon become the
      exclusive cryopreservation choice in human IVF. However, recent studies have
      clearly indicated that human embryo slow freezing, a practice considered well
      established for decades, can be significantly improved by a simple empirical
      approach. Alternatively, recent and more advanced theoretical models can predict
      oocyte responses to the diverse factors characterizing an entire slow-freezing
      procedure, offering a global method for the improvement of current protocols.
      This gives credit to the notion that oocyte slow freezing still has considerable
      margins for improvement. In human IVF, cryopreservation of oocytes has become an
      alternative to embryo storage. It has also shown enormous potential for oocyte
      donation, fertility preservation and animal biotechnology. Mouse oocytes have
      represented the elective model to develop oocyte cryopreservation in the human
      and over several decades their use has made possible the development of
      theoretical and empirical approaches. Progress in vitrification has overshadowed
      slow freezing to such an extent that it has been suggested that vitrification
      could soon become the exclusive cryopreservation choice in human IVF. However,
      recent studies have clearly indicated that human embryo slow freezing, a practice
      considered well established for decades, can be significantly improved by a
      simple empirical approach. Alternatively, recent and more advanced theoretical
      models can predict oocyte responses to the diverse factors characterizing an
      entire slow freezing procedure, offering a global method for the improvement of
      current protocols. This gives credit to the notion that oocyte slow freezing
      still has considerable margins of improvement.

PMID- 21889723
TI  - Estrogens and prostate cancer: etiology, mediators, prevention, and management.
AB  - The mainstay targets for hormonal prostate cancer (PCa) therapies are based on
      negating androgen action. Recent epidemiologic and experimental data have
      pinpointed the key roles of estrogens in PCa development and progression. Racial
      and geographic differences, as well as age-associated changes, in estrogen
      synthesis and metabolism contribute significantly to the etiology. This article
      summarizes how different estrogens/antiestrogens/estrogen mimics contribute to
      prostate carcinogenesis, the roles of the different mediators of estrogen in the
      process, and the potentials of new estrogenic/antiestrogenic compounds for
      prevention and treatment of PCa.

PMID- 21889739
TI  - Re: "ACR Appropriateness Criteria(r) on treatment of uterine leiomyomas".

PMID- 21889741
TI  - Planning for the future through intersociety collaboration.

PMID- 21889742
TI  - Reconciliation.

PMID- 21889743
TI  - The opt-out option.

PMID- 21889744
TI  - The virtues of democracy.

PMID- 21889745
TI  - Accreditation and you.

PMID- 21889746
TI  - ACR Appropriateness Criteria(r) on acute shoulder pain.
AB  - The shoulder joint is a complex array of muscles, tendons, and capsuloligamentous
      structures that has the greatest freedom of motion of any joint in the body.
      Acute (<2 weeks) shoulder pain can be attributable to structures related to the
      glenohumeral articulation and joint capsule, rotator cuff, acromioclavicular
      joint, and scapula. The foundation for investigation of acute shoulder pain is
      radiography. Magnetic resonance imaging is the procedure of choice for the
      evaluation of occult fractures and the shoulder soft tissues. Ultrasound, with
      appropriate local expertise, is an excellent evaluation of the rotator cuff, long
      head of the biceps tendon, and interventional procedures. Fluoroscopy is an
      excellent modality to guide interventional procedures. Computed tomography is an
      excellent modality for characterizing complex shoulder fractures. Computed
      tomographic arthrography or fluoroscopic arthrography may be alternatives in
      patients for whom MR arthrography is contraindicated. A multimodal approach may
      be required to accurately assess shoulder pathology. The ACR Appropriateness
      Criteria((r)) are evidence-based guidelines for specific clinical conditions that
      are reviewed every 2 years by a multidisciplinary expert panel. The guideline
      development and review include an extensive analysis of current medical
      literature from peer-reviewed journals and the application of a well-established
      consensus methodology (modified Delphi) to rate the appropriateness of imaging
      and treatment procedures by the panel. In those instances in which evidence is
      lacking or not definitive, expert opinion may be used to recommend imaging or
      treatment.

PMID- 21889747
TI  - Medical imaging data reconciliation, part 1: innovation opportunity.
AB  - The concept of data reconciliation has been well described in the industrial and
      pharmaceutical literature and is designed to ensure the integrity, reliability,
      and accuracy of sequential data in a multistep process. This concept can
      similarly be applied to the delivery of medical imaging services, which begins
      with order entry and ends with reporting and communication. The ultimate goal of
      medical imaging data reconciliation is to ensure continuity of care, extending
      across multiple service providers and imaging and information system
      technologies. The longitudinal analysis of standardized data across the imaging
      continuum presents an opportunity to improve communication between service
      providers, education and training, workflow, and clinical outcomes. In addition,
      the derived data can in turn be used to create data-driven best-practice
      guidelines and computerized decision support tools.

PMID- 21889748
TI  - The value-added services of hospital-based radiology groups.
AB  - The authors discuss the ways in which a single, cohesive, on-site radiology group
      adds value to both the processes of patient care and the success of the hospital.
      The value-added services fall into 6 categories: (1) patient safety, (2) quality
      of the images, (3) quality of the interpretations, (4) service to patients and
      referring physicians, (5) cost containment, and (6) helping build the hospital's
      business. If the hospital allows its radiology department to become fragmented by
      the intrusion of other specialists or teleradiology companies in remote
      locations, most of these added values would be lost, and chaos could ensue.

PMID- 21889749
TI  - A survey of emergency physician-performed ultrasound: implications for academic
      radiology departments.
AB  - A survey of academic radiology departments shows that the prevalence of emergency
      room physician-performed ultrasound examinations is high and that providing a
      24/7 attending radiology service leads to no significant reduction in physician
      activity.

PMID- 21889750
TI  - Automatically inserted technical details improve radiology report accuracy.
AB  - PURPOSE: To assess the effect of automatically inserted technical details on the
      concordance of a radiology report header with the actual procedure performed.
      METHODS AND MATERIALS: The study was IRB approved and informed consent was
      waived. We obtained radiology report audit data from the hospital's compliance
      office from the period of January 2005 through December 2009 spanning a total of
      20 financial quarters. A "discordance percentage" was defined as the percentage
      of total studies in which a procedure code change was made during auditing. Using
      Chi-square analysis we compared discordance percentages between reports with
      manually inserted technical details (MITD) and automatically inserted technical
      details (AITD). The second quarter data of 2007 was not included in the analysis
      as the switch from MITD to AITD occurred during this quarter. RESULTS: The
      hospital's compliance office audited 9,110 studies from 2005-2009. Excluding the
      564 studies in the second quarter of 2007, we analyzed a total of 8,546 studies,
      3,948 with MITD and 4,598 with AITD. The discordance percentage in the MITD group
      was 3.95% (156/3,948, range per quarter, 1.5- 6.1%). The AITD discordance
      percentage was 1.37% (63/4,598, range per quarter, 0.0-2.6%). A Chi-square
      analysis determined a statistically significant difference between the 2 groups
      (P < 0.001). CONCLUSION: There was a statistically significant improvement in the
      concordance of a radiology report header with the performed procedure using
      automatically inserted technical details compared to manually inserted details.

PMID- 21889751
TI  - Putting the heat back into radiology morbidity and mortality conferences.
AB  - Morbidity and mortality (M&M) conferences run the gamut from heated adversarial
      affairs seen in traditional surgery departments, to more passive versions often
      seen in radiology departments. If done well, not only can M&M conferences have
      great utility as a resident training tool, but they also can be a vehicle for
      quality improvement and allow a first impression for how a complication might be
      perceived in court. The legislature and courts have deemed candid peer review so
      essential that such proceedings have been provided with a qualified privilege. To
      maximize the benefit of M&M conferences, an emphasis on accountability and robust
      debate, preconference preparation, broader faculty attendance, and an
      understanding of the ground rules are necessary. M&M conferences also should be
      solution oriented, and practice quality improvements and teaching modules should
      regularly be generated from such conferences. An example of a potential revised
      M&M conference is outlined.

PMID- 21889752
TI  - Putting the light (not the heat) back into radiology morbidity and mortality
      conferences.

PMID- 21889753
TI  - Identifying benchmarks for discrepancy rates in preliminary interpretations
      provided by radiology trainees at an academic institution.
AB  - PURPOSE: At many academic medical centers, radiology house staff provide
      preliminary interpretations for imaging studies after hours, the accuracy and
      timely availability of which are crucial to patient care. Nevertheless, these
      preliminary interpretations are sometimes discrepant with finalized attending
      reports. The rate of such discrepancies can provide valuable information for
      quality improvement. The aim of this study was to identify specific benchmarks
      for resident discrepancy rates by reviewing all 73,072 on-call reports generated
      at the authors' institution over 1 year. METHODS: A custom-built interface called
      Orion was used to track all on-call reports generated in 2010. Reports graded as
      discrepant with major changes during attending review were automatically
      identified. The turnaround time (TAT) of all reports was measured. These data
      were used to identify specific benchmarks for resident performance on call.
      RESULTS: A total of 45,608 of 73,072 preliminary dictations (62%) were
      interpreted by residents; of these, 407 (0.89%) had major discrepancies. The
      major discrepancy rates varied among individual residents (0.2% to 1.8%),
      modalities, and level of resident training. On the basis of distributions, major
      discrepancy benchmarks were established for overall rate (1.7%) and for the
      modalities of conventional radiography (1.5%), CT (4.0%), and ultrasound (4.0%).
      The mean TAT was significantly shorter for the emergency department (46 minutes)
      than for inpatient services (144 minutes). A benchmark TAT of 1 hour has been
      adopted for all imaging studies performed through the emergency department.
      CONCLUSIONS: Identifying benchmarks for major discrepancy rates and TAT of
      preliminary interpretations by radiology trainees is a valuable first step for
      individual and departmental quality improvement.

PMID- 21889754
TI  - Enhancing same-day access to magnetic resonance imaging.
AB  - PURPOSE: The aim of this study was to provide better patient access to MRI within
      24 hours through process improvement. METHODS: The MRI process in an academic
      radiology department was examined. Customer value was determined using a Kano
      questionnaire. Current state process and performance data were measured. Process
      time and process value mapping were conducted. Underlying root causes that
      hampered MRI process flow were identified and prioritized using a fishbone
      diagram and failure mode and effect analysis. Statistical analysis, queuing
      theory, and statistical process control were used to describe and understand
      process behaviors, to test hypotheses, to validate solutions, and to monitor
      results. RESULTS: Timely access to MRI examinations within 24 hours was
      identified as a key customer value. A total of 33 failure modes leading to
      process wastes, together with 113 potential failure causes, were worked out, of
      which 14 failure modes were prioritized and dealt with. Having improved the
      process, patient access within 24 hours increased from 53% to >90%. The mean
      cycle time was reduced from 52 to 39 minutes. The monthly throughput increased by
      38%. Scanner productivity was increased by 32%. Revenue and savings are estimated
      to be about ?247,000 in the first year, after subtracting all costs. CONCLUSIONS:
      Patient access to MRI within 24 hours has been granted for >90% of requests.
      Improved productivity and cost saving are achieved simultaneously.

PMID- 21889755
TI  - Meaningful use in radiology.
AB  - With an estimated $1.5 billion in potential stimulus bonus payments for
      radiologist professionals at stake, and penalties looming farther down the road,
      radiologists would be wise to study and respond to recent federal regulations
      related to meaningful use of complete certified ambulatory electronic health
      records and their equivalents. Many radiologists mistakenly believe that they
      were "left out" of the meaningful use rewards or that compliance is technically
      impractical. With diligent preparation, including the adoption of new technology
      and workflows, the vast majority of radiologists can qualify before October 2012
      to capture the full available rewards and avoid later penalties.

PMID- 21889756
TI  - Accountable care organizations: before you jump in....

PMID- 21889757
TI  - Pointers for optimizing radiation dose in chest CT protocols.

PMID- 21889758
TI  - Investing in radiology's future: ongoing efforts by the Minnesota Radiological
      Society to promote resident participation and leadership.

PMID- 21889759
TI  - Richard Hall Chamberlain.

PMID- 21889760
TI  - [Restricted intrauterine growth: a problem of definition or content?].

PMID- 21889761
TI  - Comparison of frequencies of patent foramen ovale and thoracic aortic
      atherosclerosis in patients with cryptogenic ischemic stroke undergoing
      transesophageal echocardiography.
AB  - Studies have shown an association between the presence of a patent foramen ovale
      (PFO) and cryptogenic stroke (CS) in patients aged <55 years. In addition,
      protruding atheromatous plaques in the ascending aorta and aortic arch are an
      independent risk factor for ischemic stroke in patients aged >=55 years. The aim
      of this study was to determine the association of CS in the 2 age groups with PFO
      and with atheromatous plaques in the ascending aorta and in the aortic arch.
      Transesophageal echocardiograms in 229 patients evaluated for CS were compared to
      those in 314 patients evaluated for cardiac disease other than PFO with no
      histories of stroke (the control group). The prevalence of PFO and the presence
      of complex atheromatous plaques in the ascending aorta and aortic arch were
      determined in all patients and compared between the CS and control patients in
      the 2 age groups. The prevalence of PFO was significantly higher in patients with
      CS than in control patients among those aged <55 years (31 of 114 [27%] vs 24 of
      171 [14%], p = 0.006) and those aged >=55 years (28 of 115 [24%] vs 21 of 143
      [15%], p = 0.049). The incidence of atrial septal aneurysm was similar in the 2
      groups irrespective of patient age, as was the prevalence of complex atheromatous
      plaques. Multivariate analysis showed that PFO was independently associated with
      CS, irrespective of patient age (<55 years: odds ratio 2.4, 95% confidence
      interval 1.3 to 4.5, p = 0.01; >=55 years: odds ratio 1.9, 95% confidence
      interval 1.1 to 3.5, p = 0.03). In conclusion, PFO was significantly associated
      with CS in younger (aged <55 years) and older (aged >=55 years) patients. Atrial
      septal aneurysm and complex atheromas in the ascending aorta and aortic arch do
      not appear to be associated with CS.

PMID- 21889762
TI  - Cervical carcinomas overexpress human trophoblast cell-surface marker (Trop-2)
      and are highly sensitive to immunotherapy with hRS7, a humanized monoclonal anti
      Trop-2 antibody.
AB  - OBJECTIVE: We evaluated the expression of human trophoblast cell-surface marker
      (Trop-2) and the potential of hRS7, a humanized monoclonal anti-Trop-2 antibody,
      against treatment-refractory cervical cancer. STUDY DESIGN: Trop-2 expression was
      evaluated by immunohistochemistry, real-time polymerase chain reaction, and flow
      cytometry. Sensitivity to hRS7 antibody-dependent cell-mediated cytotoxicity
      (ADCC) and complement-dependent cytotoxicity was tested in 5-hour chromium
      release assays. The effect of interleukin (IL)-2 on hRS7 ADCC was also
      investigated. RESULTS: Membrane Trop-2 expression was observed in 8 of 8 (100%)
      of the cancer samples tested by immunohistochemistry, but not in normal cervix.
      High messenger RNA expression by real-time polymerase chain reaction and high
      Trop-2 surface expression by flow cytometry were detected in 80% of cervical
      cancers (4 of 5 cell lines). Although these tumors were resistant to natural
      killer cell-dependent cytotoxicity in vitro (mean killing, 6.0%), Trop-2-positive
      cell lines showed high sensitivity to hRS7 ADCC (range of killing, 30.6-73.2%).
      Incubation with IL-2 further increased the level of cytotoxicity against Trop-2
      positive tumors. CONCLUSION: hRS7 may represent a novel treatment option for
      patients with cervical cancer refractory to conventional treatment modalities.

PMID- 21889763
TI  - Anatomic relationships of the pudendal nerve branches.
AB  - OBJECTIVE: We sought to characterize the distribution of the pudendal nerve
      branches and to correlate findings with injury risk related to common midurethral
      sling procedures. STUDY DESIGN: Dissections were performed in 18 female cadavers.
      Biopsies were obtained to confirm gross findings by histology. RESULTS: In all
      dissections, most of the clitoral and perineal nerves coursed caudal to the
      ventral portion of the perineal membrane. The inferior rectal nerve did not enter
      the pudendal canal in 44% (n = 8) of specimens. Nerve tissue was confirmed
      histologically in tissue sampled. CONCLUSION: The clitoral and perineal branches
      of the pudendal nerve should be at low risk of direct nerve injury during
      midurethral slings and similar procedures as they course caudal to the ventral
      portion of the perineal membrane. The inferior rectal nerve might be at risk of
      injury during procedures that involve passage of needles through the ischioanal
      fossa.

PMID- 21889764
TI  - Mean, lowest, and highest pulsatility index of the uterine artery and adverse
      pregnancy outcome in twin pregnancies.
AB  - OBJECTIVE: The objective of the study was to assess the use of mean, lowest, and
      highest pulsatility index (PI) of the uterine arteries to screen for adverse
      pregnany outcome in twin pregnancies. STUDY DESIGN: This was a screening study of
      423 twin pregnancies. Relationship between PI at 20-22 weeks and adverse
      pregnancy outcome was evaluated. RESULTS: Mean, lowest, and highest PI above the
      95th centile were significant risk factors for preeclampsia and adverse pregnancy
      outcome in monochorionic and dichorionic twins. We calculated a sensitivity for
      preeclampsia for mean, highest, and lowest PI of 35%, 29%, and 27%, respectively.
      CONCLUSION: Increased mean, lowest, and highest PI is associated with a higher
      risk of preeclampsia and adverse pregnancy outcome in twins. We observed the
      highest sensitivity and specificity by using highest PI. The high incidence of
      preeclampsia in twins makes it attractive to use the PI of the uterine artery for
      risk stratification in twins.

PMID- 21889765
TI  - Risks of stress urinary incontinence and pelvic organ prolapse surgery in
      relation to mode of delivery.

PMID- 21889766
TI  - Use of expiratory CT pulmonary angiography to reduce inspiration and breath-hold
      associated artefact: contrast dynamics and implications for scan protocol.
AB  - AIM: To investigate the effects of scanning in expiration during computed
      tomography pulmonary angiography (CTPA). MATERIALS AND METHODS: One hundred and
      eighty-one consecutive expiratory CTPA examinations were compared with 145
      inspiratory CTPA examinations performed using a standardized protocol through
      assessment of attenuation seen in the cardiac chambers, pulmonary artery (PA),
      and ascending aorta. RESULTS: Expiratory scans showed greater attenuation at the
      pulmonary trunk, right PA, left PA, lobar and segmental PAs (p<0.05). Expiratory
      scans showed a lower incidence of transient contrast medium interruption
      (p<0.001) and generalized unsatisfactory PA opacification (p<0.05). Scans with
      generalized low PA attenuation had lower attenuation in the right ventricle, left
      heart, and ascending aorta (p<0.001) suggesting that contrast medium delivery or
      dilution prior to contrast medium entry into the PA is responsible. Expiratory
      scans showed lower quality scores (p<0.001) for depiction of lung parenchyma.
      CONCLUSION: Expiratory scanning could be used as an optimal protocol for
      dedicated PA imaging. However, it suffers from inferior parenchymal imaging and
      should probably be reserved for failed inspiratory breath-hold CTPA.

PMID- 21889767
TI  - Development of an automatic subsea blowout preventer stack control system using
      PLC based SCADA.
AB  - An extremely reliable remote control system for subsea blowout preventer stack is
      developed based on the off-the-shelf triple modular redundancy system. To meet a
      high reliability requirement, various redundancy techniques such as controller
      redundancy, bus redundancy and network redundancy are used to design the system
      hardware architecture. The control logic, human-machine interface graphical
      design and redundant databases are developed by using the off-the-shelf software.
      A series of experiments were performed in laboratory to test the subsea blowout
      preventer stack control system. The results showed that the tested subsea blowout
      preventer functions could be executed successfully. For the faults of
      programmable logic controllers, discrete input groups and analog input groups,
      the control system could give correct alarms in the human-machine interface.

PMID- 21889768
TI  - D-dimer testing versus multislice computed tomography in the diagnosis of
      postpartum pulmonary embolism in symptomatic high-risk women.

PMID- 21889770
TI  - Increased resting heart rate and greater progression of subclinical coronary
      atherosclerosis: another bad fact about fast hearts? Commentary on the study of
      Rubin et al.

PMID- 21889769
TI  - Variants in the APOA5 gene region and the response to combination therapy with
      statins and fenofibric acid in a randomized clinical trial of individuals with
      mixed dyslipidemia.
AB  - OBJECTIVE: Atherogenic dyslipidemia is highly associated with coronary heart
      disease and is characterized by elevated triglycerides (TG), low high-density
      lipoprotein cholesterol (HDL-C), and elevated low-density lipoprotein cholesterol
      (LDL-C). The combination of statins and fibrates is a common modality to treat
      individuals with atherogenic dyslipidemia. We sought to identify single
      nucleotide polymorphisms (SNPs) associated with HDL-C, TG, and apolipoprotein A1
      (ApoA-I) response to combination therapy with statins and fenofibric acid (FA) in
      individuals with atherogenic dyslipidemia. METHODS: 2228 individuals with mixed
      dyslipidemia who were participating in a multicenter, randomized, double-blind,
      active-controlled study comparing FA alone, in combination with a statin, or
      statin alone for a 12-week period, were genotyped for 304 candidate SNPs. A
      multivariate linear regression analysis for percent change in HDL-C, ApoA-I and
      TG levels was performed. RESULTS: SNPs in the apolipoprotein (APO) A5-ZNF259
      region rs3741298 (P = 1.8 * 10(-7)), rs964184 (P = 3.6 * 10(-6)), rs651821 (P =
      4.5 * 10(-5)), and rs10750097 (P = 1 * 10(-4)), were significantly associated
      with HDL-C response to combination therapy with statins and FA, with a similar
      association identified for ApoA-I. A haplotype composed of the minor alleles of
      SNPs rs3741298, rs964184, and rs10750097, was associated with a positive response
      to statins and FA (P = 8.7 * 10(-7)) and had a frequency of 18% in the study
      population. CONCLUSION: In a population with atherogenic dyslipidemia, common
      SNPs and haplotypes within the APOA5-ZNF259 region are highly associated with HDL
      C and ApoA-I response to combination therapy with statins and FA.

PMID- 21889771
TI  - Lack of association between IL6 single nucleotide polymorphisms and
      cardiovascular disease in Spanish patients with rheumatoid arthritis.
AB  - INTRODUCTION: Rheumatoid arthritis (RA) is a complex polygenic inflammatory
      disease associated with accelerated atherosclerosis. IL-6 is a key mediator of
      inflammation in RA. A recent study showed an association between IL6-174 G/C gene
      polymorphism and cardiovascular (CV) disease in UK individuals with RA. To
      confirm this association we assessed the influence of three IL6 gene
      polymorphisms in the risk of CV disease in a large series of patients with RA.
      MATERIAL AND METHODS: We studied 1250 Spanish patients with RA. Besides
      genotyping the traditional single nucleotide polymorphism (SNP) promoter -174G/C
      (rs1800795), we assessed another two SNPs (rs2069827 and rs2069840) located in
      the IL6 gene that were selected by SNP-tagging. RESULTS: Two-hundred and twenty
      (17.6%) of the 1250 patients experienced CV events. No significant differences in
      the genotype, allele and haplotype frequencies between RA patients with and
      without CV events were observed. CONCLUSION: Our results do not confirm in a
      Spanish population the association of IL6 gene with CV disease in RA previously
      reported in the UK.

PMID- 21889772
TI  - An analysis of the frame-content theory in babble of 9-month-old babies with
      cleft lip and palate.
AB  - The aim of this study was to examine the consonant-vowel co-occurrence patterns
      predicted by the Frame-Content theory in 16 nine-month-old babies with unrepaired
      cleft palate (+/-cleft lip) and 16 age-matched non-cleft babies. Babble from
      these babies was phonetically transcribed and grouped according to the
      intrasyllabic predictions of the theory (labial-central, alveolar-front, and
      velar-back). Both groups demonstrated the three consonant-vowel co-occurrence
      patterns predicted by the Frame-Content theory. Other patterns not predicted by
      the Frame-Content theory emerged as strong patterns as well. LEARNING OUTCOMES:
      The reader will be able to: * Describe consonant-vowel co-occurrence patterns
      produced by babies with and without cleft palate. * Describe vowel inventories of
      babies with cleft palate. * Identify possible therapy targets for babies with
      cleft palate.

PMID- 21889773
TI  - Intentional communication in nonverbal and verbal low-functioning children with
      autism.
AB  - In this study we characterized profiles of communicative functions and forms of
      children with autism and intellectual disability (n=26), as compared to typically
      developing children (n=26) with a comparable nonverbal mental age (2-5 years).
      Videotapes of the Communication and Symbolic Behavior Scales - Developmental
      Profile were analyzed using a standardized observation scheme in which three main
      functions were distinguished: behavior regulation, social interaction, and joint
      attention. Different forms of communication were also investigated: gestures,
      vocalizations/verbalizations, and eye gaze. Results indicated that in typically
      developing children the proportion of communication for the purpose of joint
      attention was much higher than for behavior regulation, whereas in children with
      autism the opposite pattern was seen. Low-functioning nonverbal children with
      autism mainly communicated for behavior regulation and not or only rarely for
      declarative purposes. Generally, this subgroup used the least complex forms to
      communicate. Low-functioning verbal children with autism differed from typically
      developing children only in the rate, not in the proportion of communication for
      specific functions. Combinations of three different communicative forms were used
      by verbal children with autism less frequently than by typically developing
      children. LEARNING OUTCOMES: After reading this paper, readers should be able to:
      (1) describe early development of communicative functions, (2) explain
      differences in communication profiles with respect to form and function between
      verbal and nonverbal low-functioning children with autism and typically
      developing children matched on nonverbal mental age and (3) discuss clinical
      implications of the findings for communication interventions in verbal and
      nonverbal low-functioning children with autism.

PMID- 21889774
TI  - Feasibility of group voice therapy for individuals with Parkinson's disease.
AB  - PURPOSE: The primary purpose was to demonstrate the feasibility of executing
      treatment tasks focused on increasing loudness in a group format for individuals
      with Parkinson's disease (PD). A second purpose was to report preliminary pre-to
      post treatment outcomes for individuals with PD immediately after they complete
      the group program. METHODS: The group intervention is described. Fifteen adults
      with PD who participated in the group and three clinicians leading the group
      provided feedback about the execution of the intervention. The participants also
      provided voice samples and self-ratings of voice handicap once before completing
      the 8-week voice group and once immediately after completing the voice group.
      Outcome measures included voice intensity, fundamental frequency (F0) mean,
      standard deviation and range, maximum phonation time, and listener judgment of
      loudness. RESULTS: Feedback from the clinicians suggested that many, but not all,
      of the voice activities could be executed within a group setting. Participants
      with PD indicated they understood the focus of the group and that subjectively
      they felt the group was helpful for increasing loudness. Statistically
      significant increases occurred for voice intensity, F0 maximum, and F0 range.
      Voice handicap scores decreased significantly and 80% of the participants were
      judged louder post intervention. CONCLUSIONS: Clinician and participant feedback
      indicated that it was feasible to execute most LSVT((r)) tasks in a group format
      with some modifications. The preliminary outcome data indicate that the targeted
      behavior (voice dB and loudness) did change in the predicted direction as did
      several other measures. Future studies comparing outcomes of group intervention
      to the gold standard LSVT((r)), and exploring retention of treatment gains over
      time, are needed. LEARNING OUTCOMES: After reading the manuscript, readers will
      be able to: (1) Describe previous attempts at group intervention to improve voice
      for individuals with Parkinson's disease. (2) List three ways that the group
      intervention tried in this study differed from LSVT((r)). (3) Identify three
      limitations to this study that must be addressed before advocating implementation
      of the group approach in clinical situations.

PMID- 21889775
TI  - Lignans as food constituents with estrogen and antiestrogen activity.
AB  - Phytoestrogens are plant-derived food ingredients assumed to contribute to the
      prevention of hormone-dependent cancers, osteoporosis, cardiovascular disease,
      and menopausal symptoms. Lignans occur in numerous food plants and various
      structures; they are common constituents of human diet, and estrogen activity has
      been assessed for lignan metabolites formed in the mammalian intestine. We
      examined natural lignans and semisynthetic norlignans for estrogen and
      antiestrogen activity. A transformed yeast strain (Saccharomyces cerevisiae)
      expressing the estrogen receptor alpha and a reporter system was applied as test
      system. Some plant lignans showed estrogen activity while others and the
      semisynthetic norlignans were moderately active antiestrogens. Docking of lignans
      to protein models of estrogen receptor alpha in the active and inactive form
      sustained the results of the yeast estrogen assay and supported the concept of
      plant lignans as phytoestrogens.

PMID- 21889776
TI  - Outcome of depression in primary care: better than expected.

PMID- 21889777
TI  - Histomolecular classification of adult diffuse gliomas: the diagnostic value of
      immunohistochemical markers.
AB  - Adult gliomas are most often infiltrative. The World Health Organization (WHO)
      has classed them into three major groups according to the presomptive cell of
      origin: astrocytoma, oligodendroglioma and mixed oligoastrocytoma. Depending on
      the presence or absence of a small number of signs of anaplasia (mitosis, nuclear
      atypia, cell density, microvascular proliferation and necrosis) the WHO
      distinguishes grade II (LGG), III (anaplastic), and IV (glioblastomas, GBM).
      Mutation in the isocitrate deshydrogenase I and II (IDH1 and 2) genes
      distinguishes grade II, III and secondary GBM from primary GBM. Moreover two
      additional genetic alterations are recorded in grade II and III gliomas: TP53
      mutations that characterize astrocytomas and 1p19q codeletion (as the result of
      t(1;19)(q10;p10) translocation) recorded in oligodendrogliomas. Mixed gliomas,
      the most non-reproducible category, share with astrocytomas and
      oligodendrogliomas the same genetic alterations. Interestingly TP53 mutation
      (p53+) and 1p19q codeletion (1p19q+) are mutually exclusive and involve IDH
      mutated (IDH+) glial precursor cells. According to IDH, TP53, and 1p19q status,
      four major subtypes of LGG are recorded: IDH+/p53-/1p19q-, IDH+/p53+/1p19q-,
      IDH+/p53-/1p19q+ and triple negative, this last subgroup having the worst
      prognosis. Interestingly, p53 expression and internexin alpha (INA) expression
      can replace to some extent TP53 mutation and 1p19 codeletion, respectively.
      Moreover the antibody directed against the IDH1R132H isoform is highly specific.
      Because this mutation is the most frequent it is sufficient to assess IDH status
      in more than 80% of grade II and III gliomas. Taken together these three
      immunohistochemical markers are contribute greatly to the classification of
      gliomas and should be tested routinely as diagnostic markers. Finally, although
      GBM are genetically heterogeneous, the vast majority display EGFR amplification,
      often associated with EGFR expression, which can be helpful for diagnosis in
      certain cases.

PMID- 21889778
TI  - Physiopathology of radiation-induced neurotoxicity.
AB  - Ionizing irradiation for the treatment of malignant brain tumors has associated
      with it a risk of inducing serious morphologic and functional deficits. While
      obvious tissue damage generally occurs after relatively high radiation doses,
      cognitive impairment can be seen after lower exposures. The mechanisms
      responsible for cognitive injury are not well understood, but may involve
      neurogenesis, a process that is affected by microenvironmental factors including
      oxidative stress and inflammation. In addition, damage to neurons, either
      directly or through environmental influences may have a profound impact on
      cognition. The relationships between cellular response, environmental factors and
      behavior are complex and difficult to study. However, understanding such issues
      should provide critical information relevant to the development of strategies and
      approaches to ameliorate or treat radiation-induced injuries that are associated
      with behavioral performance.

PMID- 21889779
TI  - [Anti-angiogenic strategies in glioblastoma].
AB  - INTRODUCTION: Glioblastoma, a highly angiogenic tumor, has poor prognosis despite
      aggressive conventional therapies combining surgery, chemotherapy and
      radiotherapy. Anti-angiogenic strategies that have recently come to the clinic,
      are the most promising therapeutic approaches for these tumors. STATE OF ART:
      Tumor hypoxia is the main trigger of angiogenesis processes driven primarily by
      vascular endothelial growth factor (VEGF). Clinical data indicate that inhibitors
      of VEGF such as bevacizumab or VEGF receptors such as tyrosine kinase inhibitors
      are of potential interest in the treatment of recurrent glioblastoma, with an
      acceptable toxicity. However, despite high rate of initial radiological response
      and rapid clinical improvement in about half of patients, therapeutic failure is
      the rule. Mechanisms of resistance remain poorly understood but an invasive
      phenotype and alternative angiogenesis factors may contribute to tumor escape.
      CONCLUSIONS AND PERSPECTIVES: Anti-angiogenic strategies already play an
      important role in the management of recurrent glioblastoma. However, optimal
      combination and schedules of angiogenic inhibitors with radiotherapy and
      chemotherapy remain to be established. Important randomized clinical trials
      currently investigate therapeutic combinations for newly diagnosed glioblastoma.

PMID- 21889780
TI  - [OMICS and biomarkers of glial tumors].
AB  - INTRODUCTION: OMICS is the term used to designate new biological sciences
      investigating a large group of molecules in biological samples. For instance,
      genomics and transcriptomics study changes in genome and transcription expression
      respectively. Numerous others OMICS are emerging (e.g. epigen-, prote-, metabol-,
      lipid-, glucid-OMICS). Support from bioinformatics and biostatistics, together
      with new molecular biology technologies for screening these large molecular
      groups (i.e. high-throughput biological arrays), has led to the development of
      these scientific fields. They help to draw relevant molecular identity cards of
      tumors. STATE OF THE ART: Glial tumors form a heterogeneous morphological and
      clinical tumor group including astrocytomas (from grade I to IV),
      oligodendrogliomas and oligoastrocytomas (grades II and III). OMICS has enabled a
      better understanding of clinical and biological behavior of these tumors
      identifying new molecular abnormalities and relevant biomarkers (i.e. diagnostic,
      prognostic, predictive of response to treatments and predisposing to gliomas).
      BRAF abnormalities are diagnostic markers in pilocytic astrocytomas and
      pleomorphic xanthoastrocytomas (duplication with rearrangement and V600E
      mutation, respectively). Translocation (1;19)(q10;p10) is associated with
      oligodendroglial phenotype and better prognosis in gliomas. MGMT promoter
      methylation is predictive of response to chemotherapy in grade IV astrocytomas
      (GBM). In GBM, high-throughput studies have discovered: genetic and genomic
      disruption of tyrosine kinase receptors, TP53 and RB signaling pathways in the
      vast majority of cases; several transcriptomic (e.g. neural, proneural, classic
      and mesenchymal), epigenomic (e.g. CpG Island Methylator phenotype versus non
      methylator phenotype) and proteomic (e.g. EGFR, PDGFR and NF1) patterns with
      biological and/or clinical impacts. Finally, OMICS have identified recurrent
      IDH1/IDH2 mutations with prognostic significance in glial tumors and five single
      nucleotide polymorphisms associated with susceptibility to gliomas (e.g. TERT,
      CCDC26, PHLDB1, RTEL1 and CDKN2A/CDKN2B). These latter data combined with already
      known inherited cancer syndromes (i.e. Turcot type 1, Cowden, melanoma
      astrocytoma, Li-Fraumeni, tuberous sclerosis complex, type I and II
      neurofibromatosis) improve our knowledge of genetic predisposition to gliomas.
      PERSPECTIVES: Data generated by OMICS are huge, multidimensional and promising.
      Bioinformatics and biostatistics will allow their integration (integromics)
      toward a precise dissection of their clinical of biological significance in neuro
      oncology. CONCLUSIONS: OMICS have a growing impact in neuro-oncology improving
      basic research in brain tumors and clinical management of patients through the
      discovery of biomarkers.

PMID- 21889781
TI  - Associations among pathogenic bacteria, parasites, and environmental and land use
      factors in multiple mixed-use watersheds.
AB  - Over a five year period (2004-08), 1171 surface water samples were collected from
      up to 24 sampling locations representing a wide range of stream orders, in a
      river basin in eastern Ontario, Canada. Water was analyzed for Cryptosporidium
      oocysts and Giardia cyst densities, the presence of Salmonella enterica
      subspecies enterica, Campylobacter spp., Listeria monocytogenes, and Escherichia
      coli O157:H7. The study objective was to explore associations among pathogen
      densities/occurrence and objectively defined land use, weather, hydrologic, and
      water quality variables using CART (Classification and Regression Tree) and
      binary logistical regression techniques. E. coli O157:H7 detections were
      infrequent, but detections were related to upstream livestock pasture density;
      20% of the detections were located where cattle have access to the watercourses.
      The ratio of detections:non-detections for Campylobacter spp. was relatively
      higher (>1) when mean air temperatures were 6% below mean study period
      temperature values (relatively cooler periods). Cooler water temperatures, which
      can promote bacteria survival and represent times when land applications of
      manure typically occur (spring and fall), may have promoted increased frequency
      of Campylobacter spp. Fifty-nine percent of all Salmonella spp. detections
      occurred when river discharge on a branch of the river system of Shreve stream
      order = 9550 was >83 percentile. Hydrological events that promote off farm/off
      field/in stream transport must manifest themselves in order for detection of
      Salmonella spp. to occur in surface water in this region. Fifty seven percent of
      L. monocytogenes detections occurred in spring, relative to other seasons. It was
      speculated that a combination of winter livestock housing, silage feeding during
      winter, and spring application of manure that accrued during winter, contributed
      to elevated occurrences of this pathogen in spring. Cryptosporidium and Giardia
      oocyst and cyst densities were, overall, positively associated with surface water
      discharge, and negatively associated with air/water temperature during spring
      summer-fall. Yet, some of the highest Cryptosporidium oocyst densities were
      associated with low discharge conditions on smaller order streams, suggesting
      wildlife as a contributing fecal source. Fifty six percent of all detections of
      >= 2 bacteria pathogens (including Campylobacter spp., Salmonella spp., and E.
      coli O157:H7) in water was associated with lower water temperatures (<~ 14 
      degrees C; primarily spring and fall) and when total rainfall the week prior to
      sampling was >~ 27 mm (62 percentile). During higher water temperatures (>~ 14 
      degrees C), a higher amount of weekly rainfall was necessary to promote detection
      of >= 2 pathogens (primarily summer; weekly rainfall ~>42 mm (>77 percentile);
      15% of all >= 2 detections). Less rainfall may have been necessary to mobilize
      pathogens from adjacent land, and/or in stream sediments, during cooler water
      conditions; as these are times when manures are applied to fields in the area,
      and soil water contents and water table depths are relatively higher. Season,
      stream order, turbidity, mean daily temperature, surface water discharge,
      cropland coverage, and nearest upstream distance to a barn and pasture were
      variables that were relatively strong and recurrent with regard to discriminating
      pathogen presence and absence, and parasite densities in surface water in the
      region.

PMID- 21889782
TI  - Impacts of China's Three Gorges Dam Project on net primary productivity in the
      reservoir area.
AB  - China's Three Gorges Dam Project (TGP) is the world's largest hydroelectric power
      project, and as a consequence the reservoir area is at risk of ecological
      degradation. This study uses net primary productivity (NPP) as an important
      indicator of the reservoir ecosystem's productivity to estimate the impacts of
      the TGP in the local resettlement region of the Three Gorges Reservoir Area
      (TGRA) over the 2000-2010 period. The modeling method is based upon the Carnegie
      Ames Stanford Approach (CASA) terrestrial carbon model and uses Moderate
      Resolution Imaging Spectroradiometer (MODIS) remote sensing data for modeling
      simulation. The results demonstrate that total NPP in the resettlement region
      decreased by 8.0% (632.8Gg) from 2000 to 2010. The impact of the TGP on NPP is
      mainly mediated by land-use change brought about by the large-scale inundation of
      land and subsequent massive resettlement of both rural and urban residents.
      Nearby resettlement, land inundation, and relocation of old urban centers and
      affiliated urban dwellers are responsible for 54.3%, 28.0%, and 5.8% respectively
      of total NPP reduction in the resettlement region over the study period. The
      major national ecological projects implemented in the TGRA since 1998 have played
      a key role in offsetting the negative impacts of the TGP on NPP in the region.

PMID- 21889783
TI  - Removal of airborne nanoparticles by membrane coated filters.
AB  - The increasing amount of nanoparticles with the development of nanotechnology
      gives rise to concerns about potential negative impact on the environment and
      health hazards posed to humans. Membrane filter is an effective media to control
      nanoparticles. Three filters coated with polytetrafluoroethylene (PTFE) membrane
      were investigated in this study. A series of experiments on the filter efficiency
      and relevant parameters such as the particle size and face velocity were carried
      out. The data show that the efficiency curves for the membrane filters
      demonstrate the typical shape of "v" for particle sizes from 10 to 300nm at face
      velocities from 0.3 to 15cm/s. Membrane filters with larger pore sizes have
      larger Most Penetrating Particles Sizes (MPPS), and the MPPS decreases with
      increasing face velocity. The efficiencies decrease with increasing face velocity
      for particle sizes from 10 to 300nm. We present the filtration efficiency data as
      a novel three-dimensional graph to illustrate its dependence on the particle size
      and face velocity. The membrane coated filter can be considered as two combined
      layers, one fibrous layer and one membrane layer. We develop a new filtration
      efficiency model which is a combination of the models for the two layers. Results
      from the model calculation agree with experimental data well. The study can help
      to optimize the filter product and to determine the operational parameters of
      filters, thus contributing to reduction of air pollution by rapidly emerging
      nanoparticles.

PMID- 21889784
TI  - Soot-driven reactive oxygen species formation from incense burning.
AB  - This study investigated the effects of reactive oxygen species (ROS) generated as
      a function of the physicochemistry of incense particulate matter (IPM), diesel
      exhaust particles (DEP) and carbon black (CB). Microscopical and elemental
      analyses were used to determine particle morphology and inorganic compounds. ROS
      was determined using the reactive dye, Dichlorodihydrofluorescin (DCFH), and the
      Plasmid Scission Assay (PSA), which determine DNA damage. Two common types of
      soot were observed within IPM, including nano-soot and micro-soot, whereas DEP
      and CB mainly consisted of nano-soot. These PM were capable of causing oxidative
      stress in a dose-dependent manner, especially IPM and DEP. A dose of IPM (36.6
      102.3MUg/ml) was capable of causing 50% oxidative DNA damage. ROS formation was
      positively correlated to smaller nano-soot aggregates and bulk metallic
      compounds, particularly Cu. These observations have important implications for
      respiratory health given that inflammation has been recognised as an important
      factor in the development of lung injury/diseases by oxidative stress. This study
      supports the view that ROS formation by combustion-derived PM is related to PM
      physicochemistry, and also provides new data for IPM.

PMID- 21889785
TI  - Size distribution and source apportionment of polycyclic aromatic hydrocarbons
      (PAHs) in aerosol particle samples from the atmospheric environment of Delhi,
      India.
AB  - Ambient aerosol particles were collected using a five-stage impactor at six
      different sites in Delhi. The impactor segregates the TSPM into five different
      sizes (viz. >10.9, 10.9-5.4, 5.4-1.6, 1.6-0.7, and <0.7MUm). Samples collected
      were chemically analyzed for all the five size ranges, for the estimation of 16
      different PAHs. The particle size distribution of PAHs was observed to be
      unimodal in nature with the highest peak towards the smallest size aerosol
      particle (<0.7MUm). The five size ranges were categorized into two broad
      categories viz. coarse (>10.9+10.9 to 5.4+5.4 to 1.6MUm) and fine (1.6 to
      0.7+<0.7MUm). It was observed that the dominant PAHs found were pyrene,
      benzo(a)pyrene, benzo(ghi)perylene and benzo(b)fluoranthene for both the coarse
      and fine fractions. Source apportionment of polycyclic aromatic hydrocarbons
      (PAHs) has been carried out using principal component analysis method (PCA) in
      both coarse and fine size modes. The major sources identified in this study,
      responsible for the elevated concentration of PAHs in Delhi, are vehicular
      emission and coal combustion. Some contribution from biomass burning was also
      observed.

PMID- 21889786
TI  - Outdoor, but not indoor, nitrogen dioxide exposure is associated with persistent
      cough during the first year of life.
AB  - BACKGROUND AND AIMS: Because their lungs and immune system are not completely
      developed, children are more susceptible to respiratory disease and more
      vulnerable to ambient pollution. We assessed the relation between prenatal and
      postnatal nitrogen dioxide (NO(2)) levels and the development of lower
      respiratory tract infections (LRTI), wheezing and persistent cough during the
      first year of life. METHODS: The study population consisted of 352 children from
      a birth cohort in Valencia, Spain. Prenatal exposure to NO(2), a marker of
      traffic related air pollution was measured at 93 sampling sites spread over the
      study area during four different sampling periods of 7 days each. It was modeled
      for each residential address through land use regression using the empirical
      measurements and data from geographic information systems. Postnatal exposure was
      measured once inside and outside each home using passive samplers for a period of
      14 days. Outcomes studied were any episode of LRTI during the child's first year
      of life diagnosed by a doctor (bronchitis, bronchiolitis or pneumonia), wheezing
      (defined as whistling sounds coming from the chest), and persistent cough (more
      than three consecutive weeks). Outcomes and potential confounders were obtained
      from structured questionnaires. Multiple logistic regression was used to identify
      associations. RESULTS: The cumulative incidence (CI) at first year of life was
      30.4% for LRTI (23.0% bronchiolitis, 11.9% bronchitis and 1.4% pneumonia), 26.1%
      for wheezing and 6.3% for persistent cough. The adjusted odds ratio (95%
      confidence interval) per 10MUg/m(3) increment in postnatal outdoor NO(2)
      concentration was 1.40 (1.02-1.92) for persistent cough. We also found some
      pattern of association with LRTI, bronchiolitis, bronchitis, wheezing and
      persistent cough in different prenatal periods, although it was not statistically
      significant. CONCLUSIONS: Our results indicate that exposure to outdoor, but not
      indoor, NO(2) during the first year of life increases the risk of persistent
      cough.

PMID- 21889787
TI  - The new era of the livestock production in Mongolia: Consequences on streams of
      the Great Lakes Depression.
AB  - Mongolia, a landlocked country of the Central Asian plateau, is experiencing a
      significant modification of herding practices coupled with an increase in
      livestock numbers. These modifications lead to increasing impacts of grazing on
      the Mongolian steppes with major consequences on the waterbodies. We researched
      the impacts of grazing intensity on the streams of the Great Lakes Depression in
      northwestern Mongolia. We assessed the level of watershed and stream bank erosion
      and the type of vegetation structure. We calculated the livestock densities per
      watershed and linked them to the stream water discharge through a new metric
      (I(CU)). I(CU) was created as a function of cattle unit density and water
      discharge, having water discharge at a stream section reflecting its location in
      the drainage and therefore accounting for the surface area drained upstream. We
      measured also the major nutrients in the stream water and researched the
      causalities between the grazing and the impairment of watersheds and streams. Our
      results suggest that the increase of livestock numbers is reaching beyond the
      grassland and affecting the stream ecosystem. Two major impacts were highlighted
      by this study, 1) the extensive watershed and stream bank erosion and 2) the
      increase in concentration of suspended particles and orthophosphate in stream
      systems. When compared with past values from literature, our results show recent
      eutrophication of the streams compared to the pre-liberalization of the herding
      activity in Mongolia (before 1991). Consequently the continued uncontrolled
      increase of livestock numbers could threaten the conservation of the Mongolian
      waterbodies, with notable consequences on the life of the nomadic population of
      the Central Asian Plateau.

PMID- 21889788
TI  - The Posidonia oceanica marine sedimentary record: A Holocene archive of heavy
      metal pollution.
AB  - The study of a Posidonia oceanica mat (a peat-like marine sediment) core has
      provided a record of changes in heavy metal abundances (Fe, Mn, Ni, Cr, Cu, Pb,
      Cd, Zn, As and Al) since the Mid-Holocene (last 4470yr) in Portlligat Bay (NW
      Mediterranean). Metal contents were determined in P. oceanica. Both, the
      concentration records and the results of principal components analysis showed
      that metal pollution in the studied bay started ca. 2800yr BP and steadily
      increased until present. The increase in Fe, Cu, Pb, Cd, Zn and As concentrations
      since ca. 2800yr BP and in particular during Greek (ca. 2680-2465cal BP) and
      Roman (ca. 2150-1740cal BP) times shows an early anthropogenic pollution rise in
      the bay, which might be associated with large- and short-scale cultural and
      technological development. In the last ca. 1000yr the concentrations of heavy
      metals, mainly derived from anthropogenic activities, have significantly
      increased (e.g. from ~15 to 47MUg g(-1) for Pb, ~23 to 95MUg g(-1) for Zn and ~8
      to 228MUg g(-1) for As). Our study demonstrates for the first time the uniqueness
      of P. oceanica meadows as long-term archives of abundances, patterns, and trends
      of heavy metals during the Late Holocene in Mediterranean coastal ecosystems.

PMID- 21889789
TI  - Toxicity and potential risk assessment of a river polluted by acid mine drainage
      in the Iberian Pyrite Belt (SW Spain).
AB  - Metal contamination from acid mine drainage (AMD) is a serious problem in the
      southwest of the Iberian Peninsula, where the Iberian Pyrite Belt is located.
      This zone contains original sulfide reserves of about 1700Mt distributed among
      more than 50 massive sulfide deposits. Weathering of these minerals releases to
      the waters significant quantities of toxic elements, which severely affect the
      sediments and surface waters of the region. The main goal of this paper is to
      evaluate the toxicity and the potential risk associated with the mining areas
      using Microtox test and different factors which assess the degree of
      contamination of the sediments and waters. For this, a natural stream polluted by
      AMD-discharge from an abandoned mine has been studied. The results show that
      elevated concentrations of Cu, As and Zn involve an important potential risk on
      the aquatic environment, associated both with sediments and waters. Microtox test
      informs that the sediments are extremely or very toxic, mainly related to
      concentrations of Fe, As, Cr, Al, Cd, Cu and Zn. Pollution is mainly transferred
      to the sediments increasing their potential toxicity. A natural creek affected by
      AMD can store a huge amount of pollution in its sediments while exhibiting a not
      very low water pH and low water metal concentration.

PMID- 21889791
TI  - Safe injection practices: keeping safety in and the "bugs" out.

PMID- 21889792
TI  - Key words: a prescriptive approach to reducing patient anxiety and improving
      safety.

PMID- 21889790
TI  - Assembly of the prothrombinase complex on the surface of human foreskin
      fibroblasts: Implications for connective tissue growth factor.
AB  - Activated factor X (FXa) and thrombin can up-regulate gene expression of
      connective tissue growth factor (CTGF/CCN2) on fibroblasts. Since tissue factor
      (TF) is expressed on these cells, we hypothesized that they may assemble the
      prothrombinase complex leading to CTGF/CCN2 upregulation. In addition, the effect
      of thrombospondin-1 (TSP1) on this reaction was evaluated. Human foreskin
      fibroblasts were incubated with purified factor VII (FVII), factor X (FX), factor
      V (FV), prothrombin and calcium in the presence and absence of TSP1. Generation
      of FXa and of thrombin were assessed using chromogenic substrates. SMAD pathway
      phosphorylation was detected via Western-blot analysis. Pre-incubation of
      fibroblasts with FVII led to its auto-activation by cell-surface expressed TF,
      which in turn in the presence of FX, FVa, prothrombin and calcium led to FXa
      (9.7+/-0.8nM) and thrombin (7.9+/-0.04 U/mL*10-3) generation. Addition of TSP1
      significantly enhanced thrombin (23.3+/-0.7 U/mL*10-3) but not FXa (8.5+/-0.6nM)
      generation. FXa and thrombin generation leads to upregulation of CTGF/CCN2. TSP1
      alone upregulated CTGF/CCN2, an effect mediated via activation of transforming
      growth factor beta (TGFbeta) as shown by phosphorylation of the SMAD pathway, an
      event blunted by using a TGFbeta receptor I inhibitor (TGFbetaRI). FXa- and
      thrombin-induced upregulation of CTGF/CCN2 was not blocked by TGFbetaRI. In
      summary, assembly of the prothrombinase complex occurs on fibroblast's surface
      leading to serine proteases generation, an event enhanced by TSP1 and associated
      with CTGF/CCN2 upregulation. These mechanisms may play an important role in human
      diseases associated with fibrosis.

PMID- 21889793
TI  - A 54-year-old woman with a "machine on my back".

PMID- 21889794
TI  - Time for action in New York on non-communicable diseases.

PMID- 21889795
TI  - Effect of alginate encapsulation on the cellular transcriptome of human islets.
AB  - Encapsulation of human islets may prevent their immune rejection when
      transplanted into diabetic recipients. To assist in understanding why clinical
      outcomes with encapsulated islets were not ideal, we examined the effect of
      encapsulation on their global gene (mRNA) and selected miRNAs (non-coding
      (nc)RNA) expression. For functional studies, encapsulated islets were
      transplanted into peritoneal cavity of diabetic NOD-SCID mice. Genomics analysis
      and transplantation studies demonstrate that islet origin and isolation centres
      are a major source of variation in islet quality. In contrast, tissue culture and
      the encapsulation process had only a minimal effect, and did not affect islet
      viability. Microarray analysis showed that as few as 29 genes were up-regulated
      and 2 genes down-regulated (cut-off threshold 0.1) by encapsulation. Ingenuity
      analysis showed that up-regulated genes were involved mostly in inflammation,
      especially chemotaxis, and vascularisation. However, protein expression of these
      factors was not altered by encapsulation, raising doubts about the
      biosignificance of the gene changes. Encapsulation had no effect on levels of
      islet miRNAs. In vivo studies indicate differences among the centres in the
      quality of the islets isolated. We conclude that microencapsulation of human
      islets with barium alginate has little effect on their transcriptome.

PMID- 21889796
TI  - Accelerated mineralization of dense collagen-nano bioactive glass hybrid gels
      increases scaffold stiffness and regulates osteoblastic function.
AB  - Plastically compressed dense collagen (DC) gels mimic the microstructural,
      mechanical, and biological properties of native osteoid. This study investigated
      the effect of hybridizing DC with osteoinductive nano-sized bioactive glass (nBG)
      particles in order to potentially produce readily implantable, and mineralizable,
      cell seeded hydrogel scaffolds for bone tissue engineering. Due to the high
      surface area of nBG and increased reactivity, calcium phosphate formation was
      immediately detected within as processed DC-nGB hybrid gel scaffolds. By day 3 in
      simulated body fluid, accelerated mineralization was confirmed through the
      homogeneous growth of carbonated hydroxylapatite on the nanofibrillar collagen
      framework. At day 7, there was a 13 fold increase in the hybrid gel scaffold
      compressive modulus. MC3T3-E1 pre-osteoblasts, three-dimensionally seeded at the
      point of nanocomposite self-assembly, were viable up to day 28 in culture. In the
      absence of osteogenic supplements, MC3T3-E1 metabolic activity and alkaline
      phosphatase production were affected by the presence of nBG, indicating
      accelerated osteogenic differentiation. Additionally, no cell-induced contraction
      of DC-nBG gel scaffolds was detected. The accelerated mineralization of rapidly
      produced DC-nBG hybrid gels indicates their potential suitability as
      osteoinductive cell delivery scaffolds for bone regenerative therapy.

PMID- 21889797
TI  - Interactions between acute lymphoblastic leukemia and bone marrow stromal cells
      influence response to therapy.
AB  - The cure rate for pediatric patients with B precursor acute lymphoblastic
      leukemia (pre-B ALL) is steadily improving, however relapses do occur despite
      initial response to therapy. To identify links between drug resistance and gene
      deregulation we used oligonucleotide microarray technology and determined in 184
      pre-B ALL specimen genes differentially expressed compared to normal CD34(+)
      specimens. We identified 20 signature genes including CTGF, BMP-2, CXCR4 and
      IL7R, documented to regulate interactions in the bone marrow. We recorded
      remarkably similar levels of expression in three independent patient cohorts, and
      found distinct patterns in cytogenetically defined subgroups of pre-B ALL. The
      canonical pathways that were affected are involved in inter- and intra-cellular
      communication, regulating signaling within the microenvironment. We tested
      experimentally whether interaction with stromal cells conferred protection to
      four drugs used in current ALL therapy, and demonstrated that bone marrow stromal
      cells significantly influenced resistance to vincristine and cytosine
      arabinoside. Compounds designed to block the identified cellular interactions
      within the bone marrow microenvironment are expected to mobilise the leukemic
      cells and make them more accessible to contemporary antileukemic agents. The data
      provide novel insight into the pathobiology of ALL and indicate new therapeutic
      targets for patients with ALL.

PMID- 21889798
TI  - Hippophagy in the UK: a failed dietary revolution.
AB  - This study explores the history of horseflesh consumption in modern Britain and
      France. It examines why horsemeat became relatively popular in France, but not
      Britain. These reasons include the active role of scientists, philanthropists,
      journalists and butchers. These figures did not actively promote horsemeat in
      Britain. These factors are as important as cultural and economic ones in
      explaining dietary transformation.

PMID- 21889799
TI  - Prevalence and risk factors of dry eye disease in Japan: Koumi study.
AB  - OBJECTIVE: To estimate the prevalence and risk factors of dry eye disease (DED)
      in a rural setting in Japan. DESIGN: Cross-sectional study. PARTICIPANTS: We
      included 3294 subjects, aged >= 40 years who were in the residential registry for
      Koumi town. INTERVENTION: Subjects in a rural mountain area, Koumi town,
      completed questionnaires designed to detect dry eye diagnosis and risk factors.
      MAIN OUTCOME MEASURES: Clinically diagnosed DED was defined as the presence of a
      previous clinical diagnosis of DED by ophthalmologists or severe symptoms of DED
      (both dryness and irritation constantly or often). Current symptoms of DED and
      possible risk factors such as age, gender, educational history, smoking history,
      alcohol drinking history, height and weight, visual display terminal (VDT) use,
      and contact lens (CL) wear, and past/current history of certain common systemic
      diseases were the main outcome measures. We used logistic regression analysis to
      examine associations between DED and other demographic factors. RESULTS: Of the
      3294 eligible residents, 2791 residents (85%) completed the questionnaire. The
      percentage of women with a composite outcome of clinically diagnosed DED or
      severe symptoms (21.6%; 95% confidence interval [CI], 19.5-23.9) was higher than
      that of men (12.5%; 95% CI, 10.7-14.5; P<0.001). A low body mass index (BMI; odds
      ratio [OR], 2.07; 95% CI, 0.98-4.39), CL use (OR, 3.84; 95% CI, 1.46-10.10), and
      hypertension (HT) (OR, 1.39; 95% CI, 0.94-2.06) were risk factors for DED in men.
      Use of a VDT (OR, 2.33; 95% CI, 1.12-4.85), CL use (OR, 3.61; 95% CI, 2.13-6.10),
      and myocardial infarction or angina were the risk factors (OR, 2.64; 95% CI, 1.51
      4.62), whereas high BMI was a preventive factor (OR, 0.69; 95% CI, 0.48-1.01) for
      DED in women. CONCLUSIONS: Among a Japanese cohort, DED leading to a clinical
      diagnosis or severe symptoms is prevalent. Use of CLs was a common dry eye risk
      factor in both genders. The condition is more prevalent in men with low BMI, HT,
      and in women with myocardial infarction or angina and VDT use. Relevant measures
      directed against the modifiable risks may provide a positive impact on public
      health and quality of life of Japanese. FINANCIAL DISCLOSURE(S): The authors have
      no proprietary or commercial interest in any materials discussed in this article.

PMID- 21889800
TI  - Randomized, controlled trial of an educational intervention to promote spectacle
      use in rural China: the see well to learn well study.
AB  - OBJECTIVE: To test an educational intervention promoting the purchase of
      spectacles among Chinese children. DESIGN: Randomized, controlled trial.
      PARTICIPANTS: Children in years 1 and 2 of all 20 junior and senior high schools
      (ages 12-17 years) in 3 rural townships in Guangdong, China. METHODS: Children
      underwent visual acuity (VA) testing, and parents of participants with presenting
      VA worse than 6/12 in either eye improving by more than 2 lines with cycloplegic
      refraction were recommended to purchase glasses. Children at 10 randomly selected
      schools received a lecture, video, and classroom demonstration promoting
      spectacle purchase. MAIN OUTCOME MEASURES: Self-reported purchase of spectacles
      (primary outcome) and observed wear or possession of newly purchased glasses
      (secondary outcome) at follow-up examinations (mean, 219 +/- 87 days after the
      baseline visit). RESULTS: Among 15 404 eligible children, examinations were
      completed for 6379 (74.6%) at intervention schools and 5044 (73.6%) at control
      schools. Spectacles were recommended for 2236 (35.1%) children at intervention
      schools and for 2212 (43.9%) at control schools. Of these, 417 (25.7%)
      intervention schools children and 537 (34.0%, P = 0.45) control schools children
      reported buying glasses. Predictors of purchase in regression models included
      female gender (P = 0.02), worse uncorrected VA (P < 0.001), and higher absolute
      value of refractive error (P = 0.001). Neither the rate of self-reported purchase
      of glasses or observed wear or possession of newly purchased glasses differed
      between control schools and intervention schools in mixed-effect logistic
      regression models. Among children not purchasing glasses, 21.7% had better-eye VA
      of worse than 6/18. CONCLUSIONS: An intervention based on extensive pilot testing
      and focus groups in the area failed to promote spectacle purchase or wear. The
      high burden of remaining uncorrected poor vision underscores the need to develop
      better interventions. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary
      or commercial interest in any materials discussed in this article.

PMID- 21889801
TI  - The Ahmed Versus Baerveldt study: one-year treatment outcomes.
AB  - OBJECTIVE: To report the 1-year treatment outcomes of the Ahmed Versus Baerveldt
      (AVB) Study. DESIGN: Multicenter randomized clinical trial. PARTICIPANTS: A total
      of 238 patients were enrolled in the study, including 124 in the Ahmed group and
      114 in the Baerveldt group. METHODS: Patients aged 18 years or older with
      uncontrolled glaucoma refractory to medicinal, laser, and surgical therapy were
      randomized to undergo implantation of an Ahmed-FP7 valve (New World Medical,
      Inc., Rancho Cucamonga, CA) or a Baerveldt-350 implant (Abbott Medical Optics,
      Inc., Santa Ana, CA), to be followed for 5 years. MAIN OUTCOME MEASURES: The
      primary outcome measure was failure, defined as intraocular pressure (IOP) out of
      target range (5-18 mmHg with >= 20% reduction from baseline) for 2 consecutive
      visits after 3 months, vision-threatening complications, additional glaucoma
      procedures, or loss of light perception. Secondary outcome measures included IOP,
      medication use, visual acuity, complications, and interventions. RESULTS: There
      were no significant differences in baseline ocular or demographic characteristics
      between the study groups with the exception of sex. Preoperatively, the study
      group had a mean IOP of 31.4 +/- 10.8 mmHg on a mean of 3.1 +/- 1.0 glaucoma
      medications with a median Snellen acuity of 20/100. The cumulative probability of
      failure a 1-year was 43% in the Ahmed group and 28% in the Baerveldt group (P =
      0.02). The mean IOP at 1 year was 16.5 +/- 5.3 mmHg in the Ahmed group and 13.6
      +/- 4.8 mmHg in the Baerveldt group (P < 0.001). The mean number of glaucoma
      medications required was 1.6 +/- 1.3 in the Ahmed group and 1.2 +/- 1.3 in the
      Baerveldt group (P = 0.03). Visual acuity was similar in both groups at all
      visits in the first year (P = 0.66). In the first year after surgery, there were
      a similar number of patients who experienced postoperative complications in the 2
      groups (45% Ahmed, 54% Baerveldt, P = 0.19), but a greater number of patients in
      the Baerveldt group required interventions (26% Ahmed vs. 42% Baerveldt, P =
      0.009). CONCLUSIONS: The Baerveldt-350 group had a higher success rate than the
      Ahmed-FP7 group after 1 year of follow-up, but required a greater number of
      interventions. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may
      be found after the references.

PMID- 21889802
TI  - The impact of depression on the treatment of obsessive-compulsive disorder:
      results from a 5-year follow-up.
AB  - BACKGROUND: Many OCD patients present with comorbid conditions, and major
      depression is one of the most frequent comorbidities observed. OCD patients with
      comorbid depression exhibit functional disability and poor quality of life.
      However, it is unclear whether depressive symptoms are predictive of treatment
      response, and debate remains whether they should be targeted in the treatment of
      comorbid patients. The current study aimed at assessing the predictive value of
      depression and OCD symptoms in the long term outcome of OCD treatment. METHODS:
      In the current study, relations between OCD and depressive symptoms were
      systematically investigated in a group of 121 OCD patients who received 16
      sessions of behavior or cognitive therapy either alone or with fluvoxamine.
      RESULTS: Depression (either as a continuous or categorical variable) was not
      predictive of treatment response in any of the treatment modalities for up to 5
      years of follow-up. Changes in OCD symptoms largely predicted changes in
      depressive symptoms but not vice versa. LIMITATIONS: Subsequent to participation
      in the RCT, almost two-thirds of the participants received some form of
      additional treatment (either pharmacological or psychological), and as a result,
      it is impossible to determine interaction effects with additional treatment
      received after the trial. CONCLUSIONS: Treatment of OCD with comorbid depression
      should focus on amelioration of OCD symptoms. When OCD treatment is successful,
      depressive symptoms are likely to ameliorate as well.

PMID- 21889803
TI  - Expression and distribution of canine antimicrobial peptides in the skin of
      healthy and atopic beagles.
AB  - Antimicrobial peptides (AMPs) are small immuno-modulatory proteins important in
      defense against pathogenic organisms. Defensins and cathelicidin are the most
      frequently studied human AMPs. An increase in AMPs in atopic humans has been
      reported recently. Our goals were to determine the distribution of AMPs and
      evaluate their mRNA and protein expression in non-lesional (Day 0), acute
      lesional skin (Day 3) and post-challenged skin after resolution of skin lesions
      (Day 10) using a canine model of atopic dermatitis (AD). All dogs were
      environmentally challenged for three consecutive days with house dust mite.
      Clinical evaluation of atopic beagles was performed using a CADESI score at each
      time point before and after environmental challenge. Skin biopsies were taken
      from six healthy and seven atopic beagles before and after allergen challenge
      (Day 0, Day 3 and Day 10). The transcription of canine cathelicidin (cCath) and
      beta-defensins (cBD)-1, -2 and -3 mRNA was quantified using quantitative-RT-PCR
      while the protein distribution of cBD2, cBD3 and cCath was detected by indirect
      immunofluorescence. A significant effect, over-time, was seen in CADESI score in
      AD beagles with an increase score after challenge (Day 3). Quantitative analysis
      showed a significant difference in mRNA transcript levels between groups (with
      atopic dogs having more than controls) for all AMPs but cBD2. No effect over time
      was evident for either group. No significant differences were seen for the AMP
      protein patterns of distribution (homogenous distribution). Although, these
      results showed no differences in AMP's localization after allergen exposure in
      each group; atopic dogs had a higher mRNA expression of AMPs when compared with
      healthy dogs, a similar finding to humans.

PMID- 21889804
TI  - Laminar chemokine mRNA concentrations in horses with carbohydrate overload
      induced laminitis.
AB  - Chemokines play a vital role in leukocyte activation and emigration that
      reportedly plays a central role in laminar injury in equine laminitis. The
      purpose of this study was to evaluate the pattern of laminar chemokine expression
      in horses in the classical carbohydrate overload (CHO)-model of laminitis.
      Laminar samples were obtained 24h following water administration in the control
      group (CON, n=8), and at the onset of fever (>= 102 degrees F, 12-22 h post CHO,
      DEV group, n=8) and at the onset of lameness (20-48 h post CHO, LAM group, n=8)
      in induced horses. Real time quantitative PCR was performed on all samples in
      order to determine laminar mRNA concentrations of both CXC chemokines (CXCL1,
      CXCL6, CXCL8) and CC chemokines (CCL2 [MCP-1], CCL3 [MIP-1alpha], and CCL8 [MCP
      2]). Data were subjected to ANOVA followed by Student-Newman-Keuls (P<0.05).
      Laminar mRNA concentrations for all CXC chemokines were increased (P<0.05) at
      both the DEV and LAM horses when compared to the control horses, whereas mRNA
      concentrations of CCL2 and CCL8 were only increased in the LAM horses when
      compared to controls and the DEV horses. When taken in context with our previous
      studies, CXCL1, CXCL6 and CXCL8 increases precede peak laminar leukocyte
      accumulation. Additionally, CCL2 and CCL8 expression corroborate previous reports
      of monocyte/macrophage accumulation in affected laminae. Compared with previous
      studies, our findings demonstrate that increased laminar CXC chemokine expression
      consistently precedes peak leukocyte accumulation and onset of lameness in CHO
      laminitis models. Chemokine antagonists may be considered as possible therapeutic
      targets to decrease the influx of leukocytes that occurs during the development
      of equine laminitis.

PMID- 21889805
TI  - Training speech-in-noise perception in mainstream school children.
AB  - OBJECTIVE: Auditory training has been advocated as a management strategy for
      children with hearing, listening or language difficulties. Because poor speech-in
      noise perception is commonly reported, previous research has focused on the use
      of complex (word/sentence) stimuli as auditory training material to improve
      sentence-in-noise perception. However, some evidence suggests that engagement
      with the training stimuli is more important than the type of stimuli used for
      training. The aim of this experiment was to assess if sentence-in-noise
      perception could be improved using simpler auditory training stimuli. METHODS: We
      recruited 41 typically developing, normal-hearing children aged 8-10 years
      divided into four groups. Groups 1-3 trained over 4 weeks (12 * 30 min sessions)
      on either: (1) pure-tone frequency discrimination (FD), (2) FD in a modulated
      noise (FDN) or, (3) mono-syllabic words in a modulated noise (WN). Group 4 was an
      untrained Control. In the training tasks, either tone frequency (Group 1), or
      tone (Group 2) or speech (Group 3) level was varied adaptively. All children
      completed pre- and post-training tests of sentence perception in modulated (SMN)
      and unmodulated (SUN) noise and a probe measure of each training task. RESULTS:
      All trained groups improved significantly on the trained tasks. Transfer of
      training occurred between FDN training and FD, WN and SMN testing, and between WN
      training and SMN testing. A significant performance suppression on the SUN test
      resulted from FD and FDN training. CONCLUSION: The pattern of training-induced
      improvement, relative to Controls, suggests that transfer of training is more
      likely when some stimulus dimensions (tone frequency, speech, modulated noise)
      are shared between training tasks and outcomes. This and the finding of
      suppressed post-training performance, relative to Controls, between tasks not
      sharing a stimulus dimension both favour the use of outcome-specific material for
      auditory training.

PMID- 21889806
TI  - The hippocampal-striatal axis in learning, prediction and goal-directed behavior.
AB  - The hippocampal formation and striatum subserve declarative and procedural
      memory, respectively. However, experimental evidence suggests that the ventral
      striatum, as opposed to the dorsal striatum, does not lend itself to being part
      of either system. Instead, it may constitute a system integrating inputs from the
      amygdala, prefrontal cortex and hippocampus to generate motivational, outcome
      predicting signals that invigorate goal-directed behaviors. Inspired by
      reinforcement learning models, we suggest an alternative scheme for computational
      functions of the striatum. Dorsal and ventral striatum are proposed to compute
      outcome predictions largely in parallel, using different types of information as
      input. The nature of the inputs to striatum is furthermore combinatorial, and the
      specificity of predictions transcends the level of scalar value signals,
      incorporating episodic information.

PMID- 21889807
TI  - Detecting and categorizing frailty status in older adults using a self-report
      screening instrument.
AB  - PURPOSE: The purpose of this study was to design and validate a self-reported
      assessment tool for the identification of frailty. MATERIALS AND METHODS: A
      thousand community-dwelling older adults (>=60 years), users of the medical
      insurance of the French national education system, received (Year 1) a postal
      questionnaire requesting information about health and socio-demographic
      characteristics. Among those who responded to the questionnaire (n=535), 398
      individuals were classified as frail, pre-frail, or robust. One year later (Year
      2), the same questionnaire was sent to this group and n=309 were returned.
      Frailty was operationalized using four criteria: low body mass index (BMI), low
      level of physical activity, and dissatisfaction with both muscle strength and
      endurance. RESULTS: Frailty constituted a single entity, different from physical
      limitation and co-morbidity. Compared with robust individuals, frail persons were
      older, had more chronic diseases, higher levels of disability and physical
      function decline. Pre-frail individuals had an intermediate distribution. Those
      people classified as either frail or pre-frail had higher frequency of
      hospitalization, and a higher probability of co-morbidity than robust. Frailty
      was also associated with higher mortality. CONCLUSIONS: Our screening tool for
      frailty was able to evidence important characteristics of this syndrome, i.e., it
      is a single entity with grades of severity which are associated with health
      problems. Detecting and categorizing frailty may lead to early therapeutic
      interventions to combat this condition.

PMID- 21889808
TI  - Predictors of smoking cessation in 50-66-year-old male Taiwanese smokers: a 7
      year national cohort study.
AB  - The study was aimed to determine the predictors of smoking cessation in 50-66
      year-old male Taiwanese smokers. The study analyzed datasets of the "Survey of
      Health and Living Status of the Elderly in Taiwan" (SHLSET), a population-based
      longitudinal cohort study conducted by the Bureau of Health Promotion of Taiwan.
      Binary logistic regression analysis was performed to determine the association of
      demographic, socioeconomic, lifestyle and health-related variables with changes
      in smoking status at baseline, or with subsequent changes in smoking status in 50
      66-year-old male Taiwanese. Functional impairment was the strongest predictor of
      quitting smoking for 50-66-year-old Taiwanese men. Other factors including a
      first hospitalization, emergency visit, or diagnosis of heart disease, quitting
      drinking, living with a spouse and older age were associated with increased
      likelihood of quitting smoking. Men with long smoking history, heavy daily
      cigarette consumption and more formal education were less likely to quit. Results
      suggest that functional decline is the major cause for quitting smoking for older
      Taiwanese men. Physical impairment and traumatic diseases that cause physical
      impairment have the most impact whereas "silent diseases" such as hypertension or
      diabetes have little impact. These findings should be useful for designing target
      specific intervention strategies for older male Taiwanese smokers.

PMID- 21889809
TI  - An evaluation of Foot-and-Mouth Disease outbreak reporting in mainland South-East
      Asia from 2000 to 2010.
AB  - Foot and Mouth Disease (FMD) is considered to be endemic throughout mainland
      South-East Asia (SEA). The South-East Asia and China FMD (SEACFMD) campaign is a
      regional control programme which has been ongoing since 1997. The programme
      encourages countries to submit reports of outbreaks regularly. This paper evolved
      from a collaboration with SEACFMD to evaluate 10 years worth of reporting. All
      publicly available outbreak reports (5237) were extracted from the ASEAN Region
      Animal Health Information System (ARAHIS) for the period from 2000 to mid 2010.
      These reports included date, outbreak location (at the province and district
      level) and serotype (if known) plus information on the outbreak size and affected
      species. Not all records had complete information on the population at-risk or
      the number of animals affected. This data was transferred into a spatially
      enabled database (along with data from other sources) and analysed using R and
      SaTScan. Outbreak serotype was unknown in 2264 (43%) of reports and some
      countries had very few laboratory confirmed cases (range <1-86%). Outbreak
      reports were standardised by number of villages in each province. Outbreak
      intensity varied however there did not appear to be a consistent pattern, nor was
      there any seasonal trend in outbreaks. Spatial and spatio-temporal cluster
      detection methods were applied. These identified significant clusters of disease
      reports. FMD is endemic across the region but is not uniformly present. ARAHIS
      reports can be regarded as indicators of disease reporting: there may be reports
      in which laboratory confirmation has not occurred, and in some cases clinical
      signs are inconsistent with FMD. This raises questions about the specificity of
      the data. Advances in decentralised testing techniques offer hope for improved
      verification of FMD as the cause of disease outbreaks. Advances in molecular
      typing may provide a substantial leap forward in understanding the circulation of
      FMD in South East Asia.

PMID- 21889810
TI  - The impact of legalized abortion on child health outcomes and abandonment.
      Evidence from Romania.
AB  - We use household survey data and a unique census of institutionalized children to
      analyze the impact of abortion legalization in Romania. We exploit the lift of
      the abortion ban in December 1989, when communist dictator Ceausescu and his
      regime were removed from power, to understand its impact on children's health at
      birth and during early childhood and whether the lift of the ban had an immediate
      impact on child abandonment. We find insignificant estimates for health at birth
      outcomes and anthropometric z-scores at age 4 and 5, except for the probability
      of low birth weight which is slightly higher for children born after abortion
      became legal. Additionally, our findings suggest that the lift of the ban had
      decreased the number of abandoned children.

PMID- 21889811
TI  - Increasing prevalence of diabetes in middle or low income residents in Louisiana
      from 2000 to 2009.
AB  - OBJECTIVE: To examine the trends in the prevalence of diabetes in patients who
      received medical care from the Louisiana State University Health Care Services
      Division (LSUHCSD) hospital system between 2000 and 2009. METHODS: The study
      population included 969,609 unique outpatients and inpatients between 2000 and
      2009. The diabetes cases were identified by using ICD-9 code (250*). The annual
      diabetes prevalence was calculated as the number of unique individuals with an
      ICD-9 diabetes during the year divided by the number of unique individuals
      visiting the LSUHCSD hospitals during the year. RESULTS: The age-standardized
      prevalence of diabetes in LSUHCSC hospital patients aged >= 20 years increased by
      36.2% during 2000-2009, from 10.5% to 14.3%. The rise in age-standardized
      prevalence of diabetes from 2000 to 2009 occurred in men (from 8.9% to 13.3%) and
      women (from 11.5% to 15.0%), and in white (from 8.9% to 13.1%), African (from
      11.7% to 15.8%) and other race Americans (from 8.2% to 10.4%). The age
      standardized prevalence of diabetes was higher in women than in men (p < 0.001).
      CONCLUSION: The annual prevalence of diabetes has dramatically increased from
      2000 to 2009 in both men and women and in all races of the population served by
      the LSUHCSD hospitals.

PMID- 21889812
TI  - Dimethylarginines in patients with type 2 diabetes mellitus: relation with the
      glycaemic control.
AB  - We tested the relationship between plasma levels of dimethylarginines (ADMA and
      SDMA) and glycaemic control in 43 type 2 diabetic patients. Type 2 diabetics with
      poor glycaemic control (HbA1c>6.5) had significantly lower SDMA and higher ADMA
      concentrations than those with well-controlled glycaemia (HbA1c<6.5).

PMID- 21889813
TI  - The foot in type 2 diabetes: is there a link between vascular calcification and
      bone mineral density?
AB  - AIMS: To examine the relationship between vascular calcification in the foot
      (FVC) and bone mineral density (BMD) in the heel of type 2 diabetes mellitus (DM)
      subjects. METHODS: 65 subjects with type 2 DM and serum creatinine<125 MUmol/l
      underwent CT scanning of the foot to assess FVC and dual energy X ray
      absorptiometry (DEXA) scan to assess heel BMD. Routine biochemistry including
      osteoprotegerin (OPG) and Receptor activator of nuclear factor kappa-B ligand
      (RANKL) was also carried out. RESULTS: The proportion of subjects with FVC was
      43%, whilst 40% had low BMD (T score<-1.0). Age, neuropathy and 25 hydroxyvitamin
      D were independent predictors of FVC. Body-weight, eGFR, 25 hydroxyvitamin D,
      OPG, and total cholesterol were independent predictors of low heel BMD. There was
      no correlation between albuminuria and BMD or FVC. There was no difference in
      heel BMD between those with FVC and those without, but those with frank
      osteoporosis were significantly more likely to have FVC than those with higher
      BMD. CONCLUSIONS: There is no clear-cut association between FVC and low BMD in
      type 2 DM with relatively well-preserved renal function. Age, neuropathy, eGFR,
      hyperlipidemia, body-weight, 25 hydroxyvitamin D and OPG play a complex role in
      their pathogenesis.

PMID- 21889814
TI  - [Childhood sarcoidosis: ophthalmological manifestations and diagnostic
      difficulties in two cases].
AB  - Sarcoidosis is a systemic expression of granuloma found in young adults, but
      which remains rare in children. Its incidence is underestimated because of the
      asymptomatic forms. Ocular involvement is present in 25% of the cases. The
      diagnosis is sometimes difficult and is based on clinical, radiological, and
      biological arguments and is confirmed by histopathological examination. The
      authors report the observations of two children, aged 5 and 10 years, discussing
      the diagnostic difficulty and most particularly, the differential diagnosis with
      tuberculosis, thereby illustrating the two forms of pediatric sarcoidosis.

PMID- 21889815
TI  - [Management of eyelid burns].
AB  - Burns are devastating injuries scarring patients, both physically and
      psychologically, for life. This remains particularly true for facial burns.
      Eyelid burns occur in about 10% of thermal injuries and is a considerable
      challenge for the reconstructive surgeon given the particular anatomy of the
      eyelids. Reconstruction of the eyelids following burn injuries has been performed
      by plastic surgeons since the earliest days of reconstructive surgery, yet a
      consensus on a treatment regime has not been reached and plastic surgeons are
      divided on the subject. Controversies exist regarding the excision and
      debridement of eschar, temporary suture and surgical tarsorrhaphy, timing of
      surgery for eyelid contraction, and the role of full and split-thickness skin
      grafts in eyelid reconstruction. This paper describes the particularities of the
      treatment of burned eyelids in our Burn Center.

PMID- 21889816
TI  - [OCT measurement of the impact of Nd:YAG laser capsulotomy on foveal thickness].
AB  - INTRODUCTION: Posterior capsular opacification is the commonest complication of
      cataract surgery. It is treated with Nd:YAG laser capsulotomy. However, after
      treatment, cases of cystoid macular edema have been reported. The purpose of this
      study was to measure the foveal thickness change after Nd:YAG capsulotomy using
      optical coherence tomography (OCT) in order to clarify the physiopathology of
      this edema. PATIENTS AND METHODS: A prospective, single-center study was
      conducted on patients who underwent Nd:YAG laser capsulotomy between May 2008 and
      November 2009. All patients received the same drug protocol after Nd:YAG
      capsulotomy (acetazolamide, apraclonidine, and rimexolone). Demographic
      parameters (age, sex, and medical history), clinical features (visual acuity,
      intraocular pressure) before and after Nd:YAG laser, and laser complications were
      analyzed. Central foveal thickness was measured by OCT (Stratus OCT 3, Zeiss).
      Data were collected before Nd:YAG laser capsulotomy and 1 week, 1 month, and 3
      months after capsulotomy. The preoperative and postoperative thicknesses were
      compared. We used a Student t-test for statistical analysis. RESULTS: Thirty eyes
      of 26 patients were analyzed. The mean foveal thickness was 209 +/- 26 MUm before
      capsulotomy, 213 +/- 23 MUm, 204 +/- 19 MUm, 213 +/- 23 MUm 1 week, 1 month, and
      3 months, respectively, after capsulotomy. The foveal thickness did not
      significantly change during the first 3 months following laser treatment. No
      complications occurred. DISCUSSION AND CONCLUSION: Macular cystoid edema was a
      classical complication after Nd:YAG capsulotomy. However, there was no
      significant increase of macular thickness shortly after Nd:YAG capsulotomy in our
      study.

PMID- 21889817
TI  - [Photodynamic therapy for chronic central serous chorioretinopathy and diffuse
      retinal epitheliopathy].
AB  - PURPOSE: To report outcomes in patients with long-standing (more than 6 months)
      chronic central serous chorioretinopathy (CSC) treated with low-fluence
      Visudyne((r)) photodynamic therapy (LFV-PDT). PATIENTS AND METHODS: The clinical,
      angiographic and optical coherence tomography (OCT) results of patients with long
      standing chronic central serous chorioretinopathy (CCSC) treated with LFV-PDT in
      the Lyon Centre Rabelais between 2002 and 2008 were retrospectively analyzed. A
      comprehensive check-up (macular syndrome signs, ETDRS best-corrected visual
      acuity [BCVA], biomicroscopy, fluorescein [FA] and indocyanine green [ICGA]
      angiographies, OCT scans) was performed before LFV-PDT treatment and 3 months
      later. Patients were then followed regularly and retreated in case of recurrence.
      The LFV-PDT treatment, with a fluence of 25 J/cm(2) at an irradiance of 300 mW,
      was guided by ICGA. RESULTS: Forty-one eyes of 34 patients (27 males; mean age:
      53 years) were included, of which 18 eyes had already been treated with laser
      photocoagulation. Several leaking points were visible on FA in most of the cases
      (n=38), mainly in the macula (35 cases). Before treatment, metamorphopsia was
      noted in 51% of the cases, intraretinal edema (IRE) was present on OCT scans in
      71%, serous retinal detachment (SRD) in 85%, and pigment epithelial detachment
      (PED) in 10%. Thirty-nine eyes had only one treatment session and one eye was
      retreated once. At 3 months after LFV-PDT, IRE was present in 15% of the cases,
      SRD in 12%, and PED in 2%. At the end of the 20-month follow-up, IRE was present
      in 14% of the cases, SRD in 15%, and PED in 0%. Macular atrophy was observed on
      OCT in most of the cases at the end of the follow-up (mean central thickness,
      144.5 MUm). Compared to the initial BCVA, at 3 months after LFV-PDT, BCVA
      decreased in 22% of the cases, stabilized in 39%, and increased in 39%, while at
      the end of the follow-up, BCVA decreased in 12% of the cases, stabilized in 17%,
      and increased in 71%. No complication was observed. DISCUSSION: LFV-PDT treatment
      for patients with long-standing chronic central serous chorioretinopathy results
      in anatomical and functional improvement (sustained disappearance of the
      exudative phenomenon in most cases and increased BCVA in more than two-thirds of
      the cases). The macular atrophy observed may be due to the treatment or the
      natural course of the disease.

PMID- 21889818
TI  - [Epidemiologic study of pediatric uveitis: a series of 49 cases].
AB  - PURPOSE: To analyze the patterns of pediatric uveitis. PATIENTS AND METHODS: A
      retrospective study of 49 children with uveitis, examined from January 2000 to
      December 2009. All patients underwent a complete ophthalmic examination and an
      etiological search; follow-up varied from six months to seven years. RESULTS: The
      mean age at onset of uveitis was 11.6 years (range, 5-14 years). The sex ratio
      was 1.04. Uveitis was bilateral in 59.20% of the patients, anterior in 22 cases
      (44.9%), intermediate in seven cases (14.3%), posterior in four cases (8.1%), and
      panuveitis was found in 16 cases (32.7%). In 57.2% of the patients, uveitis was
      idiopathic. Infectious uveitis was responsible for 14.1% of the cases, the most
      common of which were toxoplasmosis and toxocarosis. Systemic associations were
      found in 22.5%, with juvenile idiopathic arthritis in 6.2%. A specific ocular
      entity was responsible for 6.2% of the cases. Ocular complications occurred in
      65.3% of the affected eyes, the most common being cataract (24.5%) and cystoid
      macular edema (20.5%). The final visual acuity was less than 20/200 in 18%.
      CONCLUSIONS: Pediatric uveitis is rare but may cause visual loss. In our study,
      the cause of uveitis in childhood remains most often undiagnosed. Toxoplasmosis
      and toxocarosis are the most frequent infectious causes. Cataract was the most
      frequent complication. A strict ophthalmological follow-up is mandatory to
      improve the prognosis.

PMID- 21889819
TI  - [In vivo confocal microscopy (HRT-II(r)) of posterior polymorphous dystrophy
      (PPMD)].

PMID- 21889820
TI  - [Intravitreal bevacizumab pretreatment in vitrectomy for severe diabetic
      retinopathy: a series of six cases].
AB  - INTRODUCTION: Bevacizumab (Avastin((r)), Roche) is a full-length humanized
      monoclonal antibody applicable to all subtypes of vascular endothelial growth
      factor (VEGF). The purpose of this study was to report the results of its use as
      a surgical additive in severe cases of proliferative diabetic retinopathy (PDR).
      PATIENTS AND METHOD: This retrospective study focused on six eyes of six patients
      with complicated diabetic retinopathy. A vitrectomy was performed within 13.6
      days after an intravitreal bevacizumab injection of 0.1 mL (2.5mg), with
      dissection of the fibrovascular proliferation using a mono- or bimanual
      delamination technique. RESULTS: The mean follow-up after intravitreal injection
      was 13.3 months. The mean surgery time was 64 minutes. The bimanual technique was
      not necessary. Only one iatrogenic retinal tear was repaired. The intraoperative
      bleeding was negligible. No adverse events resulting from the drug nor recurrence
      were observed throughout the follow-up period. CONCLUSION: Intravitreal
      bevacizumab is useful as a surgical additive in severe cases of PDR,
      significantly improving surgical conditions. Nevertheless, its use beyond
      approved indications should be reserved for complex surgical cases.

PMID- 21889821
TI  - [Bidirectional barbed suture for bladder neck reconstruction, posterior
      reconstruction and vesicourethral anastomosis during robot assisted radical
      prostatectomy].
AB  - BACKGROUND: The urethrovesical anastomosis is a particular challenging step of
      robot assisted radical prostatectomy (RARP). Failure to achieve a watertight
      anastomosis is associated with postoperative urinary leak and its consequences,
      which include paralytic ileus, prolonged catheterization, urinary peritonitis and
      possibly re-intervention. The bidirectional barbed suture is a new technology
      that may lead to improve the quality of the urethrovesical anastomosis.
      OBJECTIVE: To present our surgical technique of urethrovesical anastomosis,
      bladder neck reconstruction and posterior reconstruction, using a bidirectional
      barbed suture. MATERIAL AND METHODS: The bladder neck reconstruction, posterior
      reconstruction and vesicourethral anastomosis were performed using a 2-0
      synthetic absorbable bidirectional monofilament barbed suture RESULTS: All cases
      were finished successfully without major complication or conversion to
      laparoscopic or open surgery. CONCLUSION: The authors successfully modified their
      RARP technique to take advantage of the properties of the bidirectional barbed
      suture. Comparative studies that evaluate objective outcomes such as leakage
      rates and operative time are needed to definitely establish the benefits of this
      device in comparison to the traditional absorbable monofilament.

PMID- 21889822
TI  - Bilateral supraclinoid aneurysms associated with progressive visual impairment.

PMID- 21889823
TI  - Cranial trepanation in The Egyptian.
AB  - INTRODUCTION: Medicine and literature have been linked from ancient times; proof
      of this shown by the many doctors who have made contributions to literature and
      the many writers who have described medical activities and illnesses in their
      works. An example is The Egyptian, the book by Mika Waltari that provides a
      masterly narration of the protagonist's medical activity and describes the
      trepanation technique. DEVELOPMENT: The present work begins with the analysis of
      trepanations since prehistory and illustrates the practice of the trepanation in
      The Egyptian. The book mentions trepanation frequently and illustrates how to
      practice it and which instruments are required to perform it. Trepanation is one
      of the oldest surgical interventions carried out as treatment for cranial trauma
      and neurological diseases, but it also had the magical and religious purpose of
      expelling the evil spirits which caused the mental illness, epilepsy, or migraine
      symptoms. CONCLUSIONS: Trepanation is a surgical practice that has been carried
      out since prehistory to treat post-traumatic epilepsy, migraine, and psychiatric
      illness. The Egyptian is a book that illustrates the trepan, the trepanation
      technique, and the required set of instruments in full detail.

PMID- 21889824
TI  - Humeral arterial access: an alternative route to the femoral artery in the
      endovascular treatment of acute stroke.

PMID- 21889825
TI  - Natural products: an evolving role in future drug discovery.
AB  - The therapeutic areas of infectious diseases and oncology have benefited from
      abundant scaffold diversity in natural products, able to interact with many
      specific targets within the cell and indeed for many years have been source or
      inspiration for the majority of FDA approved drugs. The present review describes
      natural products (NPs), semi-synthetic NPs and NP-derived compounds that have
      undergone clinical evaluation or registration from 2005 to 2010 by disease area
      i.e. infectious (bacterial, fungal, parasitic and viral), immunological,
      cardiovascular, neurological, inflammatory and related diseases and oncology.

PMID- 21889827
TI  - Telangiectasia macularis eruptive perstans (TMEP) in childhood: a case report and
      literature review.

PMID- 21889826
TI  - [Management of the risk of hepatitis B virus reactivation in patients receiving
      immunosuppressive and immunomodulatory agents in internal medicine: data from the
      REACTI-B survey and proposal for a management algorithm].
AB  - PURPOSE: [corrected] This study aimed to evaluate the screening practices and
      management of the risk of hepatitis B virus (HBV) reactivation in patients
      receiving immunosuppressive and immunomodulatory agents in internal medicine
      departments and to propose a diagnostic and therapeutic algorithm. METHODS:
      Descriptive, cross-sectional survey of the 1350 members of the French Society of
      Internal Medicine, which took place in France in January 2011 using an electronic
      questionnaire. Experts in the field of HBV infection proposed a decisional
      algorithm. RESULTS: The overall response rate was 21.5%. Screening of HBV
      infection was performed in 44%, 68% and 76% of patients receiving or prior to
      initiating corticosteroids, immunosuppressive and immunomodulatory agents,
      respectively. Among participants, 35% had been confronted with one or several
      cases of HBV reactivation, mainly in patients receiving corticosteroids (54%),
      cyclophosphamide (34%) or rituximab (33%). Chronic, inactive carriers of HBV were
      considered to be at risk of reactivation in 89% of cases, while 41% of anti-HBc
      positive patients were considered at risk. In at-risk patients initiating
      immunosuppressive and/or immunomodulatory agents, 43% of practitioners consider
      the use of pre-emptive therapy, whereas 33% treat in case of confirmed
      reactivation. Systematic HBV vaccination of seronegative patients is planned in
      less than 50% of cases. Finally, 89% of participants feel they are not
      sufficiently educated regarding the risks of HBV reactivation and its prevention.
      CONCLUSION: This survey highlights the need to improve the education of
      physicians regarding the risks of HBV reactivation prior to initiating
      corticosteroids, immunosuppressive and immunomodulatory agents, and to provide
      more specific guidelines for patients managed in internal medicine departments.

PMID- 21889828
TI  - Plasma adrenomedullin levels in children with asthma: any relation with atopic
      dermatitis?
AB  - BACKGROUND: Asthma is a chronic, inflammatory disease of the airway, and
      adrenomedullin (ADM) may have some effects against bronchoconstriction. However,
      the role(s) of ADM in asthmatic children have not been evaluated yet. The aims of
      this study were to determine if there are any changes in plasma ADM levels during
      acute asthma attack, and to search for any association between allergen
      sensitivity and ADM level in asthmatic children. METHODS: Twenty-seven children
      with acute asthma attack, ranging in age from 5 to 15 years were investigated and
      compared with 20 controls. Plasma ADM levels (ng/mL) were measured by ELISA
      method. RESULTS: No significant difference was found in ADM levels between the
      controls and patients in either the acute attack or remission period. Plasma ADM
      levels were significantly higher in the acute attack (p=0.043) compared to the
      remission period in patients who were considered as having a "severe attack"
      according to GINA (Global Initiative for Asthma) classification. There were
      statistically significant correlations between the patients' AlaTOP and Food
      Panel 7 levels and plasma ADM levels in the acute attack period (p=0.010,
      p=0.001, respectively). The ADM levels in patients with a history of atopic
      dermatitis were significantly higher in the acute attack period compared to those
      without a history of atopic dermatitis (p=0.007). CONCLUSION: We speculate that
      ADM may have a role in children with atopic dermatitis, and may also have a role
      in the immuno-inflammatory process of asthma.

PMID- 21889829
TI  - Food anaphylaxis, antiphospholipid syndrome and thrombosis.

PMID- 21889830
TI  - Evaluation of angiotensin converting enzyme gene polymorphism and susceptibility
      to bronchial asthma among Egyptians.
AB  - BACKGROUND: Angiotensin converting enzyme (ACE) is expressed at high levels in
      the lungs and plays a role in the metabolism of the endogenous peptides involved
      in asthma pathogenesis. ACE gene polymorphisms have been reported to be linked to
      asthma. However, the results are conflicting, with no reported studies on
      Egyptian asthmatics. We aimed to assess ACE gene polymorphism among Egyptian
      asthmatics, and to determine its possible association with asthma severity.
      METHODS: This case-control study was conducted on 30 adult asthmatic patients,
      and 30 healthy controls with no history of asthma or atopy. Atopic status among
      asthmatics was determined by skin prick test (SPT). Lung functions were assessed
      by spirometry. Determination of ACE genotypes was performed for all subjects.
      Total serum IgE levels were measured by ELISA. RESULTS: The frequencies of the
      DD, ID and II genotypes were 46.7%, 40%, and 13.3%, respectively among the cases,
      and 33.3%, 40%, and 26.7%, respectively among the controls. No significant
      differences in ACE genotype distribution were observed between cases and controls
      (p=0.37). Genotype distribution did not differ according to age of onset or
      severity of asthma, total serum IgE levels, SPT positivity, or number of positive
      SPT reactions. Furthermore, ACE polymorphism was not statistically different
      between asthmatic patients without any associated atopic disease and those with
      an associated atopic disease. CONCLUSION: The results of our study indicate that
      ACE gene polymorphism is not significantly associated with bronchial asthma or
      with its severity among Egyptian adults.

PMID- 21889831
TI  - Urticaria caused by dimenhydrinate.

PMID- 21889832
TI  - Dose escalation for prostate cancer radiotherapy: predictors of long-term
      biochemical tumor control and distant metastases-free survival outcomes.
AB  - BACKGROUND: Higher radiation dose levels have been shown to be associated with
      improved tumor-control outcomes in localized prostate cancer (PCa) patients.
      OBJECTIVE: Identify predictors of biochemical tumor control and distant
      metastases-free survival (DMFS) outcomes for patients with clinically localized
      PCa treated with conformal external-beam radiotherapy (RT) as well as present an
      updated nomogram predicting long-term biochemical tumor control after RT. DESIGN,
      SETTING, AND PARTICIPANTS: This retrospective analysis comprised 2551 patients
      with clinical stages T1-T3 PCa. Median follow-up was 8 yr, extending >20 yr.
      INTERVENTION: Prescription doses ranged from 64.8 to 86.4 Gy. A total of 1249
      patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation
      therapy (ADT); median duration of ADT was 6 mo. MEASUREMENTS: A proportional
      hazards regression model predicting the probability of biochemical relapse and
      distant metastases after RT included pretreatment prostate-specific antigen (PSA)
      level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A
      nomogram predicting the probability of biochemical relapse after RT was
      developed. RESULTS AND LIMITATIONS: Radiation dose was one of the important
      predictors of long-term biochemical tumor control. Dose levels < 70.2 Gy and 70.2
      79.2 Gy were associated with 2.3- and 1.3-fold increased risks of PSA relapse
      compared with higher doses. Improved PSA relapse-free survival (PSA-RFS) outcomes
      with higher doses were observed for all risk groups. Use of ADT, especially for
      intermediate- and high-risk patients, was associated with significantly improved
      biochemical tumor-control outcomes. A nomogram predicting PSA-RFS was generated
      and was associated with a concordance index of 0.67. T stage, Gleason score,
      pretreatment PSA, ADT use, and higher radiation doses were also noted to be
      significant predictors of improved DMFS outcomes. CONCLUSIONS: Higher radiation
      dose levels were consistently associated with improved biochemical control
      outcomes and reduction in distant metastases. The use of short-course ADT in
      conjunction with RT improved long-term PSA-RFS and DMFS in intermediate- and high
      risk patients; however, an overall survival advantage was not observed.

PMID- 21889833
TI  - A randomized double-blind, placebo-controlled multicenter study to evaluate the
      efficacy and safety of two doses of the tramadol orally disintegrating tablet for
      the treatment of premature ejaculation within less than 2 minutes.
AB  - BACKGROUND: Premature ejaculation (PE) is a widely observed male sexual
      dysfunction with a major impact on quality of life for many men and their sexual
      partners. OBJECTIVE: To assess the safety of tramadol orally disintegrating
      tablet (ODT) (Zertane) and its efficacy in prolonging intravaginal ejaculation
      latency time (IELT) and improving Premature Ejaculation Profile (PEP) scores.
      DESIGN, SETTING, AND PARTICIPANTS: We conducted an integrated analysis of two
      identical 12-wk randomized double-blind, placebo-controlled phase 3 trials across
      62 sites in Europe. Healthy men 18-65 yr of age with a history of lifelong PE
      according to the Diagnostic and Statistical Manual of Mental Disorders, 4th
      Edition, Text Revision, and an IELT <= 120 s were included. There were 604 intent
      to-treat subjects included in the analysis. INTERVENTION: Subjects were
      randomized to receive 1:1:1 placebo (n=200), 62 mg tramadol ODT (n=206), or 89 mg
      tramadol ODT (n=198). MEASUREMENTS: We measured overall change and fold increase
      in median IELT and the mean change in all four measures of the PEP. Differences
      across treatment groups were analyzed using Wilcoxon rank-sum tests, analysis of
      variance, and chi-square analyses. RESULTS AND LIMITATIONS: Tramadol ODT resulted
      in significant increases in median IELT compared with placebo; increases were 0.6
      min (1.6 fold), 1.2 min (2.4 fold), and 1.5 min (2.5 fold) for placebo, 62 mg
      tramadol ODT, and 89 mg tramadol ODT, respectively (p<0.001 for all comparisons).
      Men saw significantly greater improvement in all four measures of the PEP in both
      doses compared with placebo (p<0.05 for all comparisons). Tramadol ODT was well
      tolerated; study discontinuation occurred in 0%, 1.0%, and 1.6% of subjects in
      placebo, 62 mg, and 89 mg tramadol ODT groups, respectively. Limitations include
      study inclusion for men with IELT up to 120 s. CONCLUSIONS: On-demand 62mg
      tramadol ODT is an effective treatment for PE in a low and safe therapeutic dose
      and provides a new option for managing mild to severe PE.

PMID- 21889834
TI  - LESS: an acronym searching for a home.

PMID- 21889835
TI  - Prostate cancer units: the patients' perspective.

PMID- 21889836
TI  - Prostate-specific antigen-based risk assessment in younger men.

PMID- 21889838
TI  - Intraoperative MRI for transphenoidal procedures: short-term outcome for 100
      consecutive cases.
AB  - BACKGROUND: The majority of pituitary lesions are benign and can be cured with
      complete surgical resection. However, the transsphenoidal technique (the most
      common approach for pathology in this region) is limited by poor visualization
      and anatomical constraints. This can lead to incomplete tumor resection and thus
      increased recurrence rates. The use of iMRI during these procedures offers the
      advantage of radiographic confirmation during the procedure and may improve
      extent of resection. We reviewed our experience with this technology in 100
      consecutive cases and compared the outcomes to published results. METHODS: 100
      patients were treated via transnasal transsphenoidal approach using the GE Signa
      SP 0.5Tesla (double doughnut design) iMRI system between July 2002 and August
      2009 and followed prospectively. Intraoperative findings, imaging results,
      postoperative MRI and clinical outcome were evaluated to determine the extent of
      tumor resection, monitor for recurrence and determine outcome. RESULTS: There
      were 100 patients studied, 81 macroadenomas, 9 microadenomas, and 10 other
      pathological diagnosis. The average extent of resection was 96% with gross total
      resection based on iMRI in 76 patients (76%). Four patients (4%) all with
      macroadenomas greater than 4 cm experienced major perioperative complications
      (hydrocephalus 2, thalamic infarct 1, major arterial bleeding 1), six patients
      (6%) developed post-operative CSF leaks, one patient (1%) had post-operative
      worsening of visual fields, and five patients (5%) had abdominal fat graft
      infections. Nine patients (9%) including five with known residual tumor required
      post-operative adjuvant treatment during the follow-up period secondary to either
      disease progression or failure to achieve endocrinological cure. CONCLUSIONS:
      iMRI-guided transsphenoidal pituitary surgery provides the surgeon with immediate
      radiographic feedback during the procedure and aides in overcoming the
      limitations in direct visualization during such procedures. As a result of this
      it may enable surgeons to perform such procedures with fewer complications and
      increased rate of gross total resection. However, the impact of this technology
      on long-term tumor control still needs to be determined with further follow-up.

PMID- 21889839
TI  - Use of microwaves for in-situ removal of pollutant compounds from solid matrices.
AB  - Thermal treatments are the most used methods to remediate contaminated solids.
      However, they may seriously damage the otherwise recoverable matrices, especially
      when mild operating conditions cannot be used. Microwaves recently raised as a
      powerful tool in industrial engineering for their ability, among other
      advantages, to offer a selected heating, thus allowing to treat and remove only
      the undesired components of a matrix. This work approaches the microwave assisted
      thermal treatments of waste from a physical-chemical point of view. Two
      recovering operations have been performed, respectively, on a soil contaminated
      by volatile organic compounds and on a ceramic filter spoiled by soot, using two
      specially designed prototypes, both realized on pre-pilot scale. The heat and
      mass transfer balances have then been analyzed in their more general form, and
      terms related to the use of microwaves outlined. Solutions of the differential
      equations have been applied to interpret the effects of microwaves on rate and
      efficiency of the remediation processes.

PMID- 21889840
TI  - Exceptional catalytic efficiency in mineralization of the reactive textile azo
      dye (RB5) by a combination of ultrasound and core-shell nanoparticles (CdS/TiO2).
AB  - A novel composite with a core-shell structure (CdS/TiO(2)) was prepared through
      the combination of microemulsion and ultrasound (20 kHz). The degradation of
      reactive black 5 (RB5) was carried out in aqueous solution in a series of
      experiments by CdS/TiO(2) nanoparticles. This composite with mole ratio of 1/6
      has shown an exceptional sonocatalytic activity in comparison to the pure
      nanoparticles of TiO(2) and CdS. A significant decrease in the concentration of
      RB5 (~ 94%) was observed in 3 min sonication of the solution containing the core
      shell nanocomposite. While at the same time, the concentration was reduced to 4%
      under sonication without nanocomposite and 50% under UV light with nanocomposite.
      The increased catalytic activity of nanocomposite in the presence of ultrasound
      is due to the enhancement of mass transfer, cleaning and sweeping the surface of
      catalyst, and preventing the aggregation of particles. In addition, the presence
      of CdS nanoparticles in the composite acts as photosensitizer which not only
      extends the spectral response to the visible region but also reduces the charge
      recombination. The selected combined method (sonocatalysis) was able to
      decolorize and oxidize simultaneously the organic dye with a complete
      mineralization into SO(4)(2-) and NO(3)(-) ions.

PMID- 21889841
TI  - Chelating agent free-solid phase extraction (CAF-SPE) of Co(II), Cu(II) and
      Cd(II) by new nano hybrid material (ZrO2/B2O3).
AB  - New nano hybrid material (ZrO(2)/B(2)O(3)) was synthesized and applied as a
      sorbent for the separation and/or preconcentration of Co(II), Cu(II) and Cd(II)
      in water and tea leaves prior to their determination by flame atomic absorption
      spectrometry. Synthesized nano material was characterized by scanning electron
      microscope, transmission electron microscope and X-ray diffraction. The optimum
      conditions for the quantitative recovery of the analytes, including pH, eluent
      type and volume, flow rate of sample solution were examined. The effect of
      interfering ions was also investigated. Under the optimum conditions, adsorption
      isotherms and adsorption capacities have been examined. The recoveries of Co(II),
      Cu(II) and Cd(II) were 96 +/- 3%, 95 +/- 3%, 98 +/- 4% at 95% confidence level,
      respectively. The analytical detection limits for Co(II), Cu(II), and Cd(II) were
      3.8, 3.3, and 3.1 MUg L(-1), respectively. The reusability and adsorption
      capacities (32.2 mg g(-1) for Co, 46.5 mg g(-1) for Cu and 109.9 mg g(-1) for Cd)
      of the sorbent were found as satisfactory. The accuracy of the method was
      confirmed by analyzing certified reference material (GBW-07605 Tea leaves) and
      spiked real samples. The method was applied for the determination of analytes in
      tap water and tea leaves.

PMID- 21889842
TI  - Stabilization of ZnCl2-containing wastes using calcium sulfoaluminate cement:
      leaching behaviour of the solidified waste form, mechanisms of zinc retention.
AB  - To assess the potential of calcium sulfoaluminate cement to solidify and
      stabilize wastes containing high amounts of soluble zinc chloride (a strong
      inhibitor of Portland cement hydration), a simulated cemented waste form was
      submitted to leaching by pure water at a fixed pH of 7 for three months,
      according to a test designed to understand the degradation processes of cement
      pastes. Leaching was controlled by diffusion. The zinc concentration in the
      leachates always remained below the detection limit (2 MUmol/L), showing the
      excellent confining properties of the cement matrix. At the end of the
      experiment, the solid sample exhibited three zones which were accurately
      characterized: (i) a highly porous and friable surface layer, (ii) a less porous
      intermediate zone in which several precipitation and dissolution fronts occurred,
      and (iii) the sound core. Ettringite was a good tracer for degradation. The good
      retention of zinc by the cement matrix was mainly attributed to the precipitation
      of a hydrated and well crystallized phase with platelet morphology (which may
      belong to the layered double hydroxide family) at early age (<= 1 day), and to
      chemisorption onto aluminum hydroxide at later age.

PMID- 21889843
TI  - Synthesis of a novel silica-supported dithiocarbamate adsorbent and its
      properties for the removal of heavy metal ions.
AB  - Silica-supported dithiocarbamate adsorbent (Si-DTC) was synthesized by anchoring
      the chelating agent of macromolecular dithiocarbamate (MDTC) to the chloro
      functionalized silica matrix (SiCl), as a new adsorbent for adsorption of Pb(II),
      Cd(II), Cu(II) and Hg(II) from aqueous solution. The surface characterization was
      performed by FT-IR, XPS, SEM and elemental analysis indicating that the
      modification of the silica surface was successfully performed. The effects of
      media pH, adsorption time, initial metal ion concentration and adsorption
      temperature on adsorption capacity of the adsorbent had been investigated.
      Experimental data were exploited for kinetic and thermodynamic evaluations
      related to the adsorption processes. The characteristics of the adsorption
      process were evaluated by using the Langmuir, Freundlich and Dubinin-Radushkevich
      (D-R) adsorption isotherms and adsorption capacities were found to be 0.34 mmol
      g(-1), 0.36 mmol g(-1), 0.32 mmol g(-1) and 0.40 mmol g(-1) for Pb(II), Cd(II),
      Cu(II) and Hg(II), respectively. The adsorption mechanism of Hg(II) onto Si-DTC
      is quite different from that of Pb(II), Cd(II) or Cu(II) onto Si-DTC, which is
      demonstrated by the XPS and FT-IR results.

PMID- 21889844
TI  - Retention-oxidation-adsorption process for emergent treatment of organic liquid
      spills.
AB  - The feasibility and effectiveness of retention-oxidation-adsorption process (ROA)
      for the elimination of organic contaminants induced by chemical accidents were
      investigated in this study. Organobentonites (DTMA-, TTA-, CTMA- and OTMA
      bentonite), potassium ferrate (Fe(VI)), ozone and granular activated carbon (GAC)
      were used as rapid and efficient materials in the treatment and recovery of
      organic liquid spills. Results indicated that the retention capacities of
      organobentonites (especially CTMA-bentonite) were much higher than that of
      natural bentonite towards the chosen organic compounds. Additionally, pH, oxidant
      dosage, initial concentration of contaminant and chemical structure had
      significant influences on the effectiveness of the oxidation process. In a pilot
      scale experiment, the ferrate/GAC (F/G) and ozone/GAC (O/G) processes made a
      comparatively good performance in the treatment of wastewater containing aniline
      or nitrobenzene, with the removal efficiencies of the contaminants greater than
      80%. Overall, the ROA process showed a high efficiency and steady operation in
      the removal of hazardous organic liquids and subsequent clean up of the
      contaminated site.

PMID- 21889845
TI  - Removal of Ag+ from water environment using a novel magnetic thiourea-chitosan
      imprinted Ag+.
AB  - A novel, thiourea-chitosan coating on the surface of magnetite (Fe(3)O(4)) (Ag
      TCM) was successfully synthesized using Ag(I) as imprinted ions for adsorption
      and removal of Ag(I) ions from aqueous solutions. The thermal stability, chemical
      structure and magnetic property of the Ag-TCM were characterized by the scanning
      electron microscope (SEM), Fourier transform infrared spectrometer (FT-IR) and
      vibrating sample magnetometer (VSM), respectively. Batch adsorption experiments
      were performed to evaluate the adsorption conditions, selectivity and
      reusability. The results showed that the maximum adsorption capacity was 4.93
      mmol/g, observed at pH 5 and temperature 30 degrees C. Equilibrium adsorption was
      achieved within 50 min. The kinetic data, obtained at the optimum pH 5, could be
      fitted with a pseudo-second order equation. Adsorption process could be well
      described by Langmuir adsorption isotherms and the maximum adsorption capacity
      calculated from Langmuir equation was 5.29 mmol/g. The selectivity coefficient of
      Ag(I) ions and other metal cations onto Ag-TCM indicated an overall preference
      for Ag(I) ions, which was much higher than non-imprinted thiourea-chitosan beads.
      Moreover, the sorbent was stable and easily recovered, the adsorption capacity
      was about 90% of the initial saturation adsorption capacity after being used five
      times.

PMID- 21889846
TI  - Liquid-liquid extraction and flat sheet supported liquid membrane studies on
      Am(III) and Eu(III) separation using 2,6-bis(5,6-dipropyl-1,2,4-triazin-3
      yl)pyridine as the extractant.
AB  - Solvent extraction and supported liquid membrane transport studies for the
      preferential removal of Am(3+) from feeds containing a mixture of Am(3+) and
      Eu(3+) was carried out using 2,6-bis(5,6-dipropyl-1,2,4-triazin-3-yl)pyridine (n
      Pr-BTP) as the extractant. Diluent plays an important role in these studies. It
      was observed that the distribution coefficients deteriorate significantly for
      both Am(3+) and Eu(3+) though the separation factors were affected only
      marginally. The transport studies were carried out at pH 2.0 in the presence of
      NaNO(3) to result in the preferential Am(3+) transport with high separation
      factors. Effect of different experimental parameters, viz. feed composition,
      stripping agents, diluents of the organic liquid membrane and membrane pore size
      was studied on the transport and separation behaviour of Am(3+) and Eu(3+). The
      supported liquid membrane studies indicated about 85% Am(3+) and 6% Eu(3+)
      transport in 6h using 0.03 M n-Pr-BTP in n-dodecane/1-octanol (7:3) diluent
      mixture for a feed containing 1M NaNO(3) at pH 2 and a receiver phase containing
      pH 2 solution as the strippant. Consequently, a permeability coefficient of (1.75
      +/- 0.21) * 10(-4)cms(-1) was determined for the Am(3+) transport. Stability of
      the n-Pr-BTP and its SLM was also studied by carrying out the distribution and
      transport experiment after different time intervals.

PMID- 21889847
TI  - Adsorption and photocatalytic and photosensitised bleaching of acid orange 7 on
      multilayer mesoporous films of TiO2.
AB  - A series of mesoporous films of titania of different thicknesses are prepared and
      their surface areas and porosities determined by physical adsorption using Kr as
      the adsorbate. The amounts of acid orange 7 (AO7) adsorbed by these films are
      found to be proportional to their measured surface areas and so the possibility
      of using this as a method of determining the surface area of thin titania films
      is discussed. The initial rates of UV-driven photocatalytic- and visible-driven
      photosensitised-bleaching of AO7 in solution, upon UVA and visible light
      irradiation, respectively, are also directly dependent upon the measured surface
      areas of the titania films. The quantum efficiencies for the UV photocatalytic-
      and visible photosensitised-bleaching of AO7 by the thickest of the AO7 films
      were estimated to be 0.08 and 0.01%, respectively.

PMID- 21889848
TI  - CO2 sequestration by carbonation of steelmaking slags in an autoclave reactor.
AB  - Carbon dioxide (CO(2)) sequestration experiments using the accelerated
      carbonation of three types of steelmaking slags, i.e., ultra-fine (UF) slag, fly
      ash (FA) slag, and blended hydraulic slag cement (BHC), were performed in an
      autoclave reactor. The effects of reaction time, liquid-to-solid ratio (L/S),
      temperature, CO(2) pressure, and initial pH on CO(2) sequestration were
      evaluated. Two different CO(2) pressures were chosen: the normal condition (700
      psig) and the supercritical condition (1300 psig). The carbonation conversion was
      determined quantitatively by using thermo-gravimetric analysis (TGA). The major
      factors that affected the conversion were reaction time (5 min to 12h) and
      temperature (40-160 degrees C). The BHC was found to have the highest carbonation
      conversion of approximately 68%, corresponding to a capacity of 0.283 kg CO(2)/kg
      BHC, in 12h at 700 psig and 160 degrees C. In addition, the carbonation products
      were confirmed to be mainly in CaCO(3), which was determined by using scanning
      electron microscopy (SEM) and X-ray powder diffraction (XRD) to analyze samples
      before and after carbonation. Furthermore, reaction kinetics were expressed with
      a surface coverage model, and the carbon footprint of the developed technology in
      this investigation was calculated by a life cycle assessment (LCA).

PMID- 21889849
TI  - Evaluation of conventional PCR for detection of Strongylus vulgaris on horse
      farms.
AB  - Strongyle parasites are ubiquitous in grazing horses. Of these, the bloodworm
      Strongylus vulgaris is regarded as most pathogenic. Increasing levels of
      anthelmintic resistance in strongyle parasites has led to recommendations of
      decreased treatment intensities, and there is now a pronounced need for reliable
      tools for detection of parasite burdens in general and S. vulgaris in particular.
      The only method currently available for diagnosing S. vulgaris in practice is the
      larval culture, which is laborious and time-consuming, so veterinary
      practitioners most often pool samples from several horses together in one culture
      to save time. Recently, molecular tools have been developed to detect S. vulgaris
      in faecal samples. The aim of this study was to compare the performance of a
      conventional polymerase chain reaction (PCR) assay with the traditional larval
      culture and furthermore test the performance of pooled versus individual PCR for
      farm screening purposes. Faecal samples were obtained from 331 horses on 18
      different farms. Farm size ranged from 6 to 56 horses, and horses aged between 2
      months and 31 years. Larval cultures and PCR were performed individually on all
      horses. In addition, PCR was performed on 66 faecal pools consisting of 3-5
      horses each. Species-specific PCR primers previously developed were used for the
      PCR. PCR and larval culture detected S. vulgaris in 12.1 and 4.5% of individual
      horses, respectively. On the farm level, eight farms tested positive with the
      larval culture, while 13 and 11 farms were positive with the individual and
      pooled PCRs, respectively. The individual PCR method was statistically superior
      to the larval culture, while no statistical difference could be detected between
      pooled and individual PCR for farm screening. In conclusion, pooled PCR appears
      to be a useful tool for farm screening for S. vulgaris.

PMID- 21889850
TI  - Prevalence of Dirofilaria immitis infection in dogs from Dandong, China.
AB  - The aim of the present study was to estimate the prevalence and risk factors of
      Dirofilaria immitis infection in dogs from Dandong, China. A total of 886 dogs
      were examined for D. immitis infection by microscopic examination and PCR,
      indicating that the prevalence was 16.6% (213/886) and 24.0% (147/886),
      respectively. The odds of infection were significantly higher in older dogs and
      dogs sheltered in outdoor, compared to the younger ones and ones sheltered in
      indoor. No significant difference of infection was observed in different genders,
      and between pure breed and cross-breed dogs in the same rearing conditions. These
      results indicated that the risk of exposure to D. immitis in dogs is high in
      Dandong, China, and prophylaxis against the parasite is advisable to decrease the
      incidence of canine dirofilariosis.

PMID- 21889851
TI  - Molecular and functional characterization of a Schistosoma bovis annexin:
      fibrinolytic and anticoagulant activity.
AB  - Annexins belong to an evolutionarily conserved multigene family of proteins
      expressed throughout the animal and plant kingdoms. Although they are soluble
      cytosolic proteins that lack signal sequences, they have also been detected in
      extracellular fluids and have been associated with cell surface membranes, where
      they could be involved in anti-haemostatic and anti-inflammatory functions.
      Schistosome annexins have been identified on the parasite's tegument surface and
      excretory/secretory products, but their functions are still unknown. Here we
      report the cloning, sequencing, in silico analysis, and functional
      characterization of a Schistosoma bovis annexin. The predicted protein has
      typical annexin secondary and tertiary structures. Bioassays with the recombinant
      protein revealed that the protein is biologically active in vitro, showing
      fibrinolytic and anticoagulant properties. Finally, the expression of the native
      protein on the tegument surface of S. bovis schistosomula and adult worms is
      demonstrated, revealing the possibility of exposure to the host's immune system
      and thus offering a potential vaccine target for the control of schistosomiasis
      in ruminants.

PMID- 21889852
TI  - Impacts of naturally acquired protozoa and strongylid nematode infections on
      growth and faecal attributes in lambs.
AB  - On two separate sampling occasions, faecal samples were collected from lambs (2-5
      months of age) grazing pasture on two separate sheep farms in southern Western
      Australia. Live weight, body condition score (BCS), faecal consistency score
      (FCS) and faecal dry matter percentage (DM%) were measured. Faecal samples were
      screened by PCR for Cryptosporidium (18S rRNA, actin and 60 kDa glycoprotein
      [gp60] loci), Giardia duodenalis (glutamate dehydrogenase [gdh] and beta-giardin)
      and patent strongylid nematode infections (ITS-2 nuclear ribosomal DNA for
      Haemonchus contortus, Teladorsagia circumcincta, Trichostrongylus spp. Chabertia
      ovina and Oesophagostomum spp.). Faecal worm egg counts (WECs) were performed
      using a modified McMaster WEC technique. The WECs were adjusted for FCS and
      transformed using log(10)(adjusted WEC+25) prior to statistical analyses.
      Cryptosporidium, Giardia and Trichostrongylus spp. detected by PCR were
      associated with an increased risk of non-pelleted faeces (FCS >= 3.0) for both
      flocks. Cryptosporidium-positive lambs were 2.8-11.6 times more likely to have
      non-pelleted faeces and Giardia-positive lambs were 2.4-14.0 times more likely to
      have non-pelleted faeces compared to lambs negative for each respective parasite.
      Lambs positive for both Cryptosporidium and Giardia were 2.9-11.8 times more
      likely to have non-pelleted faeces than lambs positive for only one or neither of
      these parasites. Mixed internal parasite infections were found to have greater
      impacts on FCS and BCS than single infections. A higher number of internal
      parasites detected per lamb was associated with lower BCS and more loose faeces.
      The relationship between parasite detection and live weight or growth rate were
      inconsistent for both flocks. Adjusted WEC was correlated with FCS and faecal DM%
      for one flock only, although little or no correlation was found with live weight
      and growth rate for both flocks. Cryptosporidium ubiquitum and Cryptosporidium
      parvum were the most prevalent Cryptosporidium species isolated in the two
      flocks. Giardia assemblage E was the most commonly isolated genotype assemblage
      from both flocks, while assemblage A was isolated almost as frequently as
      assemblage E in the one flock. One flock was a potential source of zoonotic
      Cryptosporidium and the other flock was a potential source of zoonotic Giardia.

PMID- 21889853
TI  - Self and peer perceptions of childhood aggression, social withdrawal and
      likeability predict adult substance abuse and dependence in men and women: a 30
      year prospective longitudinal study.
AB  - While childhood behaviors such as aggression, social withdrawal and likeability
      have been linked to substance abuse outcomes in adolescence and adulthood, the
      mechanisms by which these variables relate are not yet well established. Self and
      peer perceptions of childhood behaviors in men and women were compared to assess
      the role of context in the prediction of drug and alcohol abuse and dependence.
      Participants (N=676) in an ongoing longitudinal project examining the relation
      between childhood behavior and adult mental health outcomes completed the
      Structured Clinical Interview for the DSM IV regarding their histories of
      substance abuse in mid-adulthood (mean age=34, SD=2). In women, higher levels of
      both self and peer reported aggression were associated with drug and alcohol
      abuse and dependence, and higher levels of peer reported aggression were
      associated with higher levels of alcohol abuse and dependence. As well, higher
      levels of self-perceived likeability were protective regarding substance abuse
      and dependence outcomes. In men, higher levels of peer perceived social
      withdrawal were protective regarding substance abuse and dependence outcomes.
      Findings support the comparison of self and peer perceptions of childhood
      behavior as a method of assessing the mechanisms by which childhood behaviors
      impact adult outcomes, and suggest the importance of gender in the relation
      between childhood behaviors and adult substance abuse and dependence.

PMID- 21889854
TI  - Identification of cattle, llama and horse meat by near infrared reflectance or
      transflectance spectroscopy.
AB  - Visible and near infrared reflectance spectroscopy (VIS-NIRS) was used to
      discriminate meat and meat juices from three livestock species. In a first trial,
      samples of Longissimus lumborum muscle, corresponding to beef (31) llamas (21)
      and horses (27), were homogenised and their spectra collected in reflectance
      (NIRSystems 6500 scanning monochromator, in the range of 400-2500 nm). In the
      second trial, samples of meat juice (same muscle) from the same species (20 beef,
      19 llama and 19 horse) were scanned in folded transmission (transflectance).
      Discriminating models (PLS regression) were developed against "dummy" variables,
      testing different mathematical treatments of the spectra. Best models indentified
      the species of almost all samples by their meat (reflectance) or meat juice
      (transflectance) spectra. A few (three of beef and one of llama, for meat
      samples; one of beef and one of horse, for juice samples) were classified as
      uncertain. It is concluded that NIRS is an effective tool to recognise meat and
      meat juice from beef, llama and horses.

PMID- 21889855
TI  - Characterization and clonal grouping of pathogenic Escherichia coli isolated from
      intestinal contents of diarrheic piglets in Villa Clara province, Cuba, according
      to their antibiotic resistance and ERIC-PCR profiles.

PMID- 21889856
TI  - Administration of a gonadotropin-releasing hormone antagonist to mares at
      different times during the luteal phase of the estrous cycle.
AB  - The GnRH antagonist cetrorelix was given during the early (Days 1-5), mid (Days 6
      10 or 5-12) or for the entire (Days 1-16) luteal phase of mares to inhibit the
      secretion of FSH and LH (Day 0=ovulation). Frequent blood sampling from Day 6 to
      Day 14 was used to determine the precise time-course of the suppression
      (cetrorelix given Days 6-10). Cetrorelix treatment caused a decrease in FSH and
      LH concentrations by 8 and 16 h, respectively, and an obliteration of the
      response to exogenous GnRH given 24h after treatment onset. Treatment never
      suppressed gonadotropin concentrations to undetectable levels; e.g. frequent
      sampling showed that the nadirs reached in FSH and LH were 46.2+/-6% and 33.1+/
      11%, respectively, of pre-treatment concentrations. Daily FSH concentrations were
      decreased in all treatment groups but daily LH concentrations were lower only
      when treatment commenced at the beginning of the luteal phase; progesterone
      concentrations depended on the time of cetrorelix administration, but the changes
      suggested a role for LH in corpus luteum function. The inter-ovulatory interval
      was longer than controls when cetrorelix was given in the mid- or for the entire
      luteal phase, but was unaffected by treatment in the early phase. Nevertheless,
      in all groups, FSH concentrations were higher (P<0.05 when compared to Day 0,
      subsequent ovulation) approximately 6-10 days before this next ovulation. This
      consistent relationship suggests a stringent requirement for a GnRH-induced
      elevation of FSH above a threshold at, but only at, this time; i.e. approximately
      6-10 days before ovulation.

PMID- 21889857
TI  - Cervical cancer in Indigenous women: The case of Australia.
AB  - Globally, health inequities between Indigenous and non-Indigenous populations
      exist. The disparity in health outcomes between Indigenous and non-Indigenous
      Australians is exemplified by cervical cancer. Current evidence suggests that
      Indigenous women have higher age standardised incidence and mortality than non
      Indigenous women when adjusted for stage at diagnosis and co-morbidities;
      however, there is little information pertaining to national estimates of cervical
      cancer in Indigenous women. In this paper we review available evidence on the
      difference in occurrence and case fatality of cervical cancer among Indigenous
      and non-Indigenous Australian women. The Australian Bureau of Statistics,
      Australian Institute of Health and Welfare, and State- or Territory-based Cancer
      Registries were utilised to collect surveillance data. To corroborate existing
      data, further available journal literature was identified through Medline and
      Embase. All papers selected for review were cross-referenced to identify further
      relevant studies. The most recent national estimate of age-standardised cervical
      cancer incidence rate was 16.9 and 7.1 per 100,000 women-years in Indigenous and
      non-Indigenous women respectively (incidence ratio 2.4). The Indigenous age
      standardised mortality rate was 9.9 per 100,000 women years (95% CI 7.1-13.3),
      over 5 times the non-Indigenous rate. Cervical cancer incidence, in both
      Indigenous and non-Indigenous women, has decreased since 1991. Despite the
      decline, age-standardised incidence among Indigenous women is still higher than
      non-Indigenous women. The pattern of cervical cancer incidence and survival
      corroborates the health inequities that exist in Australia. Indigenous women are
      more likely than non-Indigenous women to develop cervical cancer and are less
      likely to survive it. Similar patterns exist in Indigenous populations worldwide,
      such as New Zealander Maoris and Canadian Aboriginals, suggesting that high rates
      of cervical cancer incidence and mortality may be a symptom of social and
      economic inequity.

PMID- 21889858
TI  - Embryonal rhabdomyosarcoma of the head and neck in an adult.
AB  - OBJECTIVE: This report describes an exceedingly rare case of adult embryonal
      rhabdomyosarcoma arising in the head and neck, which was initially diagnosed as a
      primary unknown cancer. METHOD: The patient underwent a radical neck dissection
      with the total excision of the tumor, which was diagnosed as embryonal
      rhabdomyosarcoma. RESULT: The patient received intensive adjuvant chemotherapy,
      and is still alive with no signs of recurrence or metastasis. CONCLUSION: This
      case report demonstrates not only the rarity of this neoplasm but the importance
      of the differential diagnosis for planning the therapeutic strategy.

PMID- 21889859
TI  - [Influence of malnutrition on childhood mortality in a rural hospital in Rwanda].
AB  - BACKGROUND: Recent estimates of the role of malnutrition on childhood mortality
      have led to a call for action by decision makers in the fight against child
      malnutrition. Further evaluation is needed to assess the burden of malnutrition
      in terms of morbidity and mortality, as well as to assess the impact of various
      interventions. The objective of this study is to determine the effect of
      malnutrition on mortality in a pediatric service of a rural hospital in Rwanda.
      METHODS: A prospective cohort study included children aged 6-59 months coming
      from the catchment area of the hospital and admitted to the pediatric ward
      between January 2008 and June 2009. Anthropometric, clinical and biological data
      were gathered at the time of admission. The effect of malnutrition at the time of
      admission on mortality during hospitalization was analyzed by using logistic
      regression. RESULTS: At the time of admission, the prevalences of wasting,
      underweight and stunting among children was 14.2%, 37.5% and 57.3% respectively.
      Fifty-six children died during hospitalization. The period mortality rate was
      6.9%. After adjustment for age, sex, malaria thick smear and breathing with chest
      retractions, death was associated with underweight and stunting with adjusted
      odds rations of 4.6 (IC95% 2.5-8.4) and 4.0 (IC95% 2.0-8.2) respectively.
      CONCLUSION: The study confirmed the influence of malnutrition on child mortality
      in pediatrics wards. These results can be of great help for improving the
      awareness of the community decision-makers in the fight to prevent malnutrition.

PMID- 21889860
TI  - Permeability to macromolecular contrast media quantified by dynamic MRI
      correlates with tumor tissue assays of vascular endothelial growth factor (VEGF).
AB  - PURPOSE: To correlate dynamic MRI assays of macromolecular endothelial
      permeability with microscopic area-density measurements of vascular endothelial
      growth factor (VEGF) in tumors. METHODS AND MATERIAL: This study compared tumor
      xenografts from two different human cancer cell lines, MDA-MB-231 tumors (n=5),
      and MDA-MB-435 (n=8), reported to express respectively higher and lower levels of
      VEGF. Dynamic MRI was enhanced by a prototype macromolecular contrast medium
      (MMCM), albumin-(Gd-DTPA)35. Quantitative estimates of tumor microvascular
      permeability (K(PS); MUl/min * 100 cm(3)), obtained using a two-compartment
      kinetic model, were correlated with immunohistochemical measurements of VEGF in
      each tumor. RESULTS: Mean K(PS) was 2.4 times greater in MDA-MB-231 tumors
      (K(PS)=58 +/- 30.9 MUl/min * 100 cm(3)) than in MDA-MB-435 tumors (K(PS)=24 +/-
      8.4 MUl/min * 100 cm(3)) (p<0.05). Correspondingly, the area-density of VEGF in
      MDA-MB-231 tumors was 2.6 times greater (27.3 +/- 2.2%, p<0.05) than in MDA-MB
      435 cancers (10.5 +/- 0.5%, p<0.05). Considering all tumors without regard to
      cell type, a significant positive correlation (r=0.67, p<0.05) was observed
      between MRI-estimated endothelial permeability and VEGF immunoreactivity.
      CONCLUSION: Correlation of MRI assays of endothelial permeability to a MMCM and
      VEGF immunoreactivity of tumors support the hypothesis that VEGF is a major
      contributor to increased macromolecular permeability in cancers. When applied
      clinically, the MMCM-enhanced MRI approach could help to optimize the appropriate
      application of VEGF-inhibiting therapy on an individual patient basis.

PMID- 21889861
TI  - Halorubellus salinus gen. nov., sp. nov. and Halorubellus litoreus sp. nov.,
      novel halophilic archaea isolated from a marine solar saltern.
AB  - Two extremely halophilic archaeal strains GX3(T) and GX26(T) were isolated from
      the Gangxi marine solar saltern near the Weihai city of Shandong Province, China.
      Cells from the two strains were pleomorphic and stained Gram-negative, colonies
      were red-pigmented. Strains GX3(T) and GX26(T) were able to grow at 25-50 
      degrees C (optimum 37  degrees C), at 1.4-5.1M NaCl (optimum 3.1M), at pH 5.5-9.5
      (optimum pH 7.0) and neither strain required Mg(2+) for growth. Cells lyse 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 PA (phosphatidic acid), PG
      (phosphatidylglycerol), PGP-Me (phosphatidylglycerol phosphate methyl ester) and
      three major glycolipids (GL1, GL2 & GL3) chromatographically identical to S-TGD-1
      (sulfated galactosyl mannosy glucosyl diether), S-DGD-1 (sulfated mannosyl
      glucosyl diether), and DGD-1 (mannosyl glucosyl diether) respectively, an
      unidentified lipid (GL4) was also detected in strain GX26(T). Phylogenetic
      analysis based on 16S rRNA gene revealed that strain GX3(T) and strain GX26(T)
      formed a distinct clade with the closest relative, Haladaptatus paucihalophilus
      (89.9-92.4% and 90.4-92.7, respectively). The rpoB' gene similarities between
      strains GX3(T) and GX26(T), and between the two strains and the closest relative,
      Halorussus rarus TBN4(T) are 96.5%, 84.3% and 83.9%, respectively. The DNA G+C
      contents of strain GX3(T) and strain GX26(T) are 67.3 mol% and 67.2 mol%,
      respectively. The DNA-DNA hybridization value between strain GX3(T) and strain
      GX26(T) was 44%. The phenotypic, chemotaxonomic and phylogenetic properties
      suggest that strain GX3(T) and strain GX26(T) represent two novel species in a
      new genus within the family Halobacteriaceae, Halorubellus salinus gen. nov., sp.
      nov. (type strain GX3(T)=CGMCC 1.10384(T)=JCM 17115(T)) and Halorubellus litoreus
      sp. nov. (type strain GX26(T)=CGMCC 1.10386(T)=JCM 17117(T)).

PMID- 21889863
TI  - Response to letter to the editor and commentary to "'And then one day he'd shot
      himself. Then I was really shocked': general practitioners' reaction to patient
      suicide".

PMID- 21889862
TI  - The bacterial microbiota in the ceca of Capercaillie (Tetrao urogallus) differs
      between wild and captive birds.
AB  - The diet of wild capercaillie differs strongly between seasons. Particularly
      during winter, when energy demands are high and the birds forage solely on
      coniferous needles, microbial fermentations in the ceca are considered to
      contribute significantly to the energy requirement and to the detoxification of
      the resinous diet. Here, we present the first cultivation-independent analysis of
      the bacterial community in the cecum of capercaillie, using the 16S rRNA gene as
      a molecular marker. Cloning and fingerprinting analyses of cecum feces show
      distinct differences between wild and captive birds. While certain lineages of
      Clostridiales, Synergistetes, and Actinobacteria are most prevalent in wild
      birds, they are strongly reduced in individuals raised in captivity. Most
      striking is the complete absence of Megasphaera and Synergistes species in
      captive capercaillie, which are characterized by a large abundance of
      Gammaproteobacteria closely related to members of the genus Anaerobiospirillum,
      bacteria that are commonly connected with intestinal dysfunction. The community
      profiles of cecum content from wild birds differed between summer and winter
      season, and the cecum wall may be an important site for bacterial colonization.
      Our results corroborate the hypothesis that the bacterial community in the ceca
      of tetraonid birds changes in response to their highly specialized seasonal
      diets. Moreover, we propose that the observed differences in community profiles
      between wild and captive capercaillie reflects a disturbance in the bacterial
      microbiota that compromises the performance of the cecum and may be responsible
      for the high mortality of captive birds released into nature.

PMID- 21889864
TI  - Further validation of the 5-item Perceived Efficacy in Patient-Physician
      Interactions (PEPPI-5) scale in patients with osteoarthritis.
AB  - OBJECTIVE: To examine the structural validity, internal consistency, test-retest
      reliability, and construct validity of the 5-item Perceived Efficacy in Patient
      Physician Interactions (PEPPI-5) scale in patients with osteoarthritis (OA).
      METHODS: A cross-sectional sample of 224 outpatients with OA completed a survey
      containing the Dutch PEPPI-5 and other standardized measures assessing perceived
      health-management skills, general self-efficacy, social support, and health
      related quality of life. A subsample of 100 patients completed the PEPPI-5 again
      approximately 3 weeks later. RESULTS: Confirmatory factor analysis demonstrated
      good fit for a unidimensional model of the PEPPI-5. Additionally, the scale
      showed high internal consistency (alpha=0.92) and fair test-retest reliability
      (ICC=0.68). As hypothesized, the PEPPI-5 was strongly correlated with perceived
      health-management skills, moderately with social support and psychosocial aspects
      of health, and not with physical aspects of health. Contrary to expectations,
      however, it was not correlated with general self-efficacy. CONCLUSION: The Dutch
      PEPPI-5 demonstrated adequate validity and reliability in patients with OA.
      PRACTICE IMPLICATIONS: The PEPPI-5 is a brief and appropriate tool for measuring
      self-efficacy of patients with OA to interact with their physicians. Additional
      research into its sensitivity to change is needed before it can be confidently
      recommended as an outcome measure in intervention studies.

PMID- 21889866
TI  - Supporting self management--a necessity in diabetes healthcare.

PMID- 21889865
TI  - A conceptual model of the role of communication in surrogate decision making for
      hospitalized adults.
AB  - OBJECTIVE: To build a conceptual model of the role of communication in decision
      making, based on literature from medicine, communication studies and medical
      ethics. METHODS: We proposed a model and described each construct in detail. We
      review what is known about interpersonal and patient-physician communication,
      described literature about surrogate-clinician communication, and discussed
      implications for our developing model. RESULTS: The communication literature
      proposes two major elements of interpersonal communication: information
      processing and relationship building. These elements are composed of constructs
      such as information disclosure and emotional support that are likely to be
      relevant to decision making. We propose these elements of communication impact
      decision making, which in turn affects outcomes for both patients and surrogates.
      Decision making quality may also mediate the relationship between communication
      and outcomes. CONCLUSION: Although many elements of the model have been studied
      in relation to patient-clinician communication, there is limited data about
      surrogate decision making. There is evidence of high surrogate distress
      associated with decision making that may be alleviated by communication-focused
      interventions. More research is needed to test the relationships proposed in the
      model. PRACTICE IMPLICATIONS: Good communication with surrogates may improve both
      the quality of medical decisions and outcomes for the patient and surrogate.

PMID- 21889867
TI  - The "50% rule" in arthroscopic and orthopaedic surgery.
AB  - The "50% rule" is used commonly to guide treatment of partial tears of tendons
      and ligaments. The purpose of this study was to examine the history and validity
      of the 50% rule in arthroscopic and orthopaedic surgery. A PubMed search yielded
      1,039 articles that were reviewed to identify the origins of the 50% rule for
      hand flexor tendon lacerations, partial anterior cruciate ligament tears, partial
      thickness rotator cuff tears, and partial injuries of the long head of the biceps
      tendon. The rule appears to have evolved from the hand literature toward somewhat
      arbitrary application for other orthopaedic conditions. Little scientific
      information is available to support the 50% rule for these disparate entities. In
      our Level V opinion, the 50% rule allows surgeons to use subjective discretion in
      the management of prevalent orthopaedic conditions but there is very little
      scientific support for this ubiquitous decision-making criterion.

PMID- 21889868
TI  - Posterior shoulder dislocation: systematic review and treatment algorithm.
AB  - PURPOSE: Posterior shoulder dislocations (PSDs) comprise a small subset of
      shoulder dislocations, and there are few evidence-based treatment protocols and
      no actual algorithm for the treatment of PSDs available in the literature. This
      article provides a systematic review of the literature, as well as an overview of
      clinical and radiologic diagnostic techniques, and presents an algorithm for
      treatment of PSDs, including minimally invasive treatment options. METHODS: For a
      systematic review of current literature, a systematic search was performed in the
      Medline and Cochrane databases. Journal articles published between January 1940
      and June 2010 were taken into account. Studies that only existed as abstracts
      were not included in the analysis. Broad exclusion criteria consisted of
      radiologic reports, review articles, case reports, and technical notes. Refined
      exclusion criteria consisted of a minimum of 4 patients with PSDs operated on by
      the same surgical technique and clinical outcome documented by a functional
      shoulder score. RESULTS: The final set of articles for evaluating closed or open
      techniques included 5 prospective case series and 6 retrospective studies. Within
      this group, there was no study with a level of evidence higher than Level IV. We
      present a descriptive comparison of these studies because of the heterogeneity
      and/or number of patients and the level of evidence. Case reports illustrate the
      different surgical approaches according to the literature. CONCLUSIONS: PSDs are
      still a challenge for the treating physician. There are few articles available
      about PSDs in evidence-based literature, with a limited number of cases. Our
      algorithm provides guidelines for decision making including minimally invasive
      treatment options according to the available literature. LEVEL OF EVIDENCE: Level
      IV, systematic review of Level IV studies.

PMID- 21889869
TI  - Comparisons of femoral tunnel position and length in anterior cruciate ligament
      reconstruction: modified transtibial versus anteromedial portal techniques.
AB  - PURPOSE: We aimed to compare the modified transtibial and anteromedial (AM)
      portal techniques of anterior cruciate ligament reconstruction with respect to
      femoral tunnel position and length, as well as to identify factors associated
      with tunnel length. METHODS: After exclusions, 105 primary anterior cruciate
      ligament reconstructions (55 in transtibial group and 50 in AM portal group) were
      studied. Femoral tunnel positions were assessed on postoperative tunnel-view
      radiographs, and tunnel lengths were measured during surgery. Differences between
      femoral tunnel positions in the coronal plane and lengths in these 2 groups were
      examined, and factors associated with tunnel lengths were investigated. RESULTS:
      The AM portal group had a significantly more oblique femoral tunnel position than
      the transtibial group. However, femoral tunnels in the AM portal group were
      substantially shorter than tunnels in the transtibial group (34.2 v 43.3 mm, P <
      .001); the proportions of knees with femoral tunnels measuring less than 30 mm in
      the AM portal and transtibial groups were 26% and only 2%, respectively. In
      addition, a more oblique femoral tunnel position and a shorter distal femur
      mediolateral width were found to be significantly associated with a shorter
      femoral tunnel. CONCLUSIONS: This study shows that the AM portal technique can
      achieve a more oblique femoral tunnel position but that resultant tunnels are
      substantially shorter than tunnels produced by the modified transtibial
      technique.

PMID- 21889870
TI  - [Towards the end of eponyms in medicine].

PMID- 21889871
TI  - Not everything that is hot on a staging bone scan is malignant: a pictorial
      review of benign causes of increased isotope uptake.

PMID- 21889872
TI  - Complete dislodgement of a femoral component of a knee arthroplasty and expulsion
      through an infected sinus.
AB  - This is an unusual presentation of complete loosening of an infected femoral
      component of a knee arthroplasty and expulsion of the metal foreign body out of
      the body.

PMID- 21889873
TI  - Refractive outcomes after cataract surgery: Scheimpflug keratometry versus
      standard automated keratometry in virgin corneas.
AB  - PURPOSE: To compare pupil size-based Scheimpflug Holladay equivalent keratometry
      with conventional automated keratometry in refractive outcomes after cataract
      surgery in patients with virgin corneas. SETTING: Private practice, Lombard,
      Illinois, USA. DESIGN: Comparative case series. METHODS: Two groups had
      phacoemulsification with implantation of a posterior chamber intraocular lens
      (IOL). Both had immersion ultrasound biometry. The study group had Scheimpflug
      keratometry based on pupil size. The control group had conventional automated
      keratometry. The IOL power was calculated with the Holladay 2 formula.
      Statistical analysis of the refractive outcomes and the keratometry (K) readings
      was performed. RESULTS: The study group comprised 76 patients (110 eyes) and the
      control group, 94 patients (137 eyes). The mean average K reading was 43.45
      diopters (D) in the study group and 43.51 D in the control group; the difference
      was not statistically significant (P=.779). The mean absolute refractive error
      was 0.480 D in the study group and 0.252 D in the control group; the difference
      was statistically significant (P<.001). In the study group, 77 eyes were within
      +/- 0.50 D of the intended postoperative refraction, 28 were between +/- 0.50 D
      and +/- 1.00 D, 4 were between +/- 1.00 D and +/- 1.50 D, and 1 was between +/-
      1.50 D and +/- 2.00 D. In the control group, 131 eyes were within +/- 0.50 D, 3
      were between +/- 0.50 D and +/- 1.00 D, and 3 were between +/- 1.00 D and +/-
      1.50 D. The between-group difference was statistically significant (P<.001).
      CONCLUSION: Conventional automated keratometry gave better refractive outcomes
      after cataract surgery than pupil-based Scheimpflug keratometry. FINANCIAL
      DISCLOSURE: No author has a financial or proprietary interest in any material or
      method mentioned.

PMID- 21889874
TI  - Phacoemulsification cataract surgery in a large cohort of diabetes patients:
      visual acuity outcomes and prognostic factors.
AB  - PURPOSE: To assess visual acuity outcomes after phacoemulsification cataract
      surgery in a large population of diabetic patients with all degrees of diabetic
      retinopathy. SETTING: Diabetology and ophthalmology unit, Copenhagen, Denmark.
      DESIGN: Cohort study. METHODS: This review of prospectively collected data
      comprised patients who had small-incision phacoemulsification cataract surgery
      between 1999 and 2008 (10 years) according to the Danish National Patient
      Registry. RESULTS: Data of 7323 diabetic patients were reviewed. Of these
      patients, 285 had cataract surgery. The corrected distance visual acuity (CDVA)
      increased significantly after cataract surgery (P<.001; P<.05 in all diabetic
      retinopathy categories). The postoperative CDVA outcome was positively correlated
      with preoperative CDVA and negatively correlated with the degree of diabetic
      retinopathy and age (P<.001). Patients with a history of focal laser treatment
      for clinically significant macular edema had a higher risk for not gaining from
      cataract surgery (P=.04; relative risk, 1.6). In post hoc analysis, the
      proportion of patients in the cohort without diabetic retinopathy appeared to
      increase the year before cataract surgery (P=.03) and decrease the year after
      cataract surgery (P<.001). CONCLUSIONS: The CDVA increased significantly after
      phacoemulsification cataract surgery in diabetic patients regardless of the
      degree of diabetic retinopathy. The apparent progression in diabetic retinopathy
      after modern cataract surgery seems to reflect the masking of low grades of
      diabetic retinopathy by preoperative lens opacities. FINANCIAL DISCLOSURE: No
      author has a financial or proprietary interest in any material or method
      mentioned.

PMID- 21889875
TI  - Hoarding behaviors among nonclinical elderly adults: correlations with hoarding
      cognitions, obsessive-compulsive symptoms, and measures of general
      psychopathology.
AB  - This study examines correlates of hoarding behaviors among nonclinical elderly
      adults, focusing upon hoarding cognitions, obsessive-compulsive symptoms, and
      measures of general psychopathology. Two hundred and sixty-nine adults aged 56-93
      years (M=72.49 years) completed the Saving Inventory-Revised, Savings Cognitions
      Inventory-Revised, Obsessive Compulsive Inventory-Revised, Social Interaction
      Anxiety Scale, Penn State Worry Questionnaire, and Beck Depression Inventory. Our
      geriatric sample evidenced significantly greater severity of hoarding behaviors
      than did a younger community sample (24-72 years; M=44.4 years; Frost, Steketee,
      & Grishman, 2004). Within our sample, moderate correlations were found between
      hoarding behaviors and hoarding cognitions; however, controlling for obsessive
      compulsive and depressive symptoms resulted in reduced-magnitude associations. As
      well, relationships between obsessive-compulsive symptoms and both hoarding
      behaviors and hoarding cognitions were generally strong, with most relationships
      diminishing after controlling for depressive symptoms. Associations between
      hoarding symptoms and symptoms of social anxiety, general worry, and depression
      were generally moderate. A significant regression model showed depressive
      symptoms explaining the most unique variance in hoarding behaviors. Findings
      confirm a relatively greater severity of hoarding behaviors in older adults (as
      compared to younger adults) and suggest that related psychopathology plays a
      critical role in hoarding expression among older adults. As well, the current
      study contributes to the ongoing investigation of the diagnostic categorization
      of compulsive hoarding.

PMID- 21889876
TI  - The effects of high molecular weight hyaluronic acid (Hylan G-F 20) on
      experimentally induced temporomandibular joint osteoartrosis: part II.
AB  - The aim of this study was to determine the efficacy of Hylan G-F 20 on
      experimentally induced osteoarthritic changes in rabbit temporomandibular joint
      (TMJ). A 3mg/ml concentration of sodium mono iodoacetate (MIA) had been injected
      into both joints of 24 rabbits to create osteoartrosis. The study group was
      injected with Hylan G-F 20 in one joint and saline in the contralateral joint as
      a control (once a week for 3 weeks). Histological changes in articular cartilage,
      osteochondral junction, chondrocyte appearance and subchondral bone were
      determined at 4, 6, and 8 weeks. Regarding cartilage, there was a statistically
      significant difference between the two groups at 4 weeks. Degenerative bony
      changes to subchondral bone were significantly higher in the controls. No
      statistical difference was found in the study group at 6 weeks. A positive
      correlation was found between osteochondral junction and subchondral bone in the
      study group at 8 weeks. The changes in chondrocyte appearance were significantly
      decreased in the study group at all follow-up times. Intra-articular injection of
      Hylan G-F 20 decreased cartilage changes in early stage TMJ osteoartrosis and
      clustering of chondrocytes showed the chondroprotective effects of Hylan G-F 20
      caused by hypertrophic responses.

PMID- 21889877
TI  - Factors leading to failure to diagnose acute aortic dissection in the emergency
      room.
AB  - BACKGROUND: Acute aortic dissection (AAD) is often missed on initial assessment.
      PURPOSE: The aim of our study was to identify features associated with
      misdiagnosis of AAD. METHODS AND RESULTS: We examined a total of 109 emergency
      room (ER) patients who were ultimately diagnosed with AAD. Misdiagnosis of AAD
      was defined as failure to diagnose AAD at the end of the initial assessment in
      the ER, and occurred in 17 patients (16%). The alternate diagnosis consisted of
      acute coronary syndrome (n=10), other cardiovascular disease (n=3), abdominal
      disease (n=3), and cerebral infarction (n=1). In the misdiagnosed patients, walk
      in mode of admission to the ER (29% vs. 10%, p=0.042) and anterior chest pain
      (71% vs. 41%, p=0.025) were more frequent, and widened mediastinum (25% vs. 55%,
      p=0.023) was less frequent than in diagnosed patients. The number of imaging
      studies performed per patient was also fewer in misdiagnosed patients than in
      diagnosed patients (0.82 +/- 0.81 vs. 1.53 +/- 0.52, p<0.001). However, there was
      no significant difference in in-hospital mortality (18% vs. 15%, p=0.520).
      Multivariate analysis showed that the strongest predictor of misdiagnosis was
      walk-in mode of admission (odds ratio 4.777; 95% confidence interval 1.267
      18.007; p=0.021). CONCLUSIONS: Both diversity of symptoms and variability of the
      severity of symptoms, especially walk-in mode of admission lead ER physicians to
      miss AAD in about 1 in 6 cases of AAD. It is therefore important to keep AAD as a
      differential diagnosis in mind, even when patients present with mild enough
      symptoms that allow them to walk into the ER.

PMID- 21889878
TI  - Double-blind comparison of the safety and efficacy of lurasidone and ziprasidone
      in clinically stable outpatients with schizophrenia or schizoaffective disorder.
AB  - BACKGROUND: Lurasidone is a new atypical antipsychotic agent with high affinity
      for D(2), 5-HT(2A) and 5-HT(7) receptors. The current study evaluated the safety
      and efficacy of lurasidone and ziprasidone in stable outpatients diagnosed with
      schizophrenia or schizoaffective disorder. METHODS: Adult outpatients who met DSM
      IV criteria for schizophrenia or schizoaffective disorder that was chronic (>=6
      months duration) and stable were randomized to 21 days of double-blind treatment
      with a fixed dose of lurasidone 120 mg once daily (N=150) or ziprasidone 80 mg
      BID (N=151). Changes from baseline in efficacy measures were evaluated using
      mixed model for repeated measures (MMRM) analyses. RESULTS: The proportion of
      patients who discontinued from the study was similar for lurasidone and
      ziprasidone (32.5% vs. 30.7%); the proportion who discontinued due to adverse
      events was similar (10.4% vs. 11.1%). Treatment with lurasidone and ziprasidone
      was associated with a small endpoint reduction in median weight (-0.65 kg vs. 
      0.35 kg) and median total cholesterol (-6.4 vs. -4.4 mg/dL); no endpoint change
      was observed in median triglycerides (0.0 vs. 0.0 mg/dL). There were no
      clinically significant changes in other laboratory or ECG parameters. Improvement
      was observed on an MMRM analysis of the PANSS total score for lurasidone and
      ziprasidone at Week 1 (-4.1 vs. -1.6; P=0.020), Week 2, (-6.1 vs. -3.6; P=0.074),
      and Week 3 (-6.3 vs. -4.5; P=0.229). CONCLUSION: In this double-blind, fixed-dose
      comparison of lurasidone 120 mg and ziprasidone 160 mg, treatment with lurasidone
      was well-tolerated and safe, and was not associated with clinically significant
      changes from baseline in weight, metabolic parameters, or QTc interval. Study
      limitations include the relatively short trial duration and lack of placebo
      control.

PMID- 21889879
TI  - The roles of P- and E-selectins and P-selectin glycoprotein ligand-1 in primary
      and metastatic mouse melanomas.
AB  - BACKGROUND: Malignant melanoma is often accompanied by a host response of
      inflammatory cell infiltration that is highly regulated by multiple adhesion
      molecules. OBJECTIVE: To evaluate the role of adhesion molecules, including P
      selectin glycoprotein ligand-1 (PSGL-1), P-selectin, and E-selectin. METHODS:
      Subcutaneous primary growth and metastasis to the lung of B16 melanoma cells were
      examined in mice lacking PSGL-1, P-selectin, or E-selectin. RESULTS: Primary
      subcutaneous growth of B16 melanoma was augmented by loss of PSGL-1, P-selectin,
      or E-selectin, while pulmonary metastasis was reduced by the loss of E-selectin.
      The enhancement of subcutaneous tumor growth was associated with a reduced
      accumulation of natural killer cells, CD4(+) T cells and CD8(+) T cells, while
      the attenuation of pulmonary metastasis was related to the numbers of CD8(+) T
      cells. The expressions of transforming growth factor (TGF)-beta and interleukin
      (IL)-6 were correlated with primary subcutaneous growth; TGF-beta, IL-6, and
      interferon-gamma were related to number of metastatic lung nodules. Cytotoxicity
      against melanoma cells in splenocytes and in tumor-draining lymph node cells were
      not defective by the absence of adhesion molecules, suggesting that the
      enhancement of tumor growth and metastasis caused by the loss of selectins
      results from an impaired migration of effector cells into the tissue.
      CONCLUSIONS: The results indicate the complexity of anti-tumor responses mediated
      by adhesion molecules in primary subcutaneous tumors and pulmonary metastasis of
      murine experimental melanoma.

PMID- 21889880
TI  - (18)FDG PET/CT is a powerful tool for detecting subclinical arthritis in patients
      with psoriatic arthritis and/or psoriasis vulgaris.

PMID- 21889882
TI  - Pseudomonas aeruginosa and carbapenems: the urgent need to harmonise disagreeing
      breakpoints.

PMID- 21889883
TI  - Poly (N-isopropylacrylamide)/poly (ethylene oxide) blend nanofibrous scaffolds:
      thermo-responsive carrier for controlled drug release.
AB  - A facile electrospinning method has been utilized to fabricate poly (N
      isopropylacrylamide) (PNIPAM)/poly (ethylene oxide) (PEO) blend nanofibers having
      the mean fiber diameters from approximately 250 to 380 nm. Scanning electron
      microscopy (SEM) images showed that the morphology and diameter distribution of
      the nanofibrous scaffolds can be easily modulated by changing the weight ratio of
      PNIPAM/PEO in electrospinning solution. X-ray diffraction (XRD) and
      thermogravimetric analysis (TGA) demonstrated that there were interactions
      between the molecules of PNIPAM and PEO. Vitamin B12 was chosen as a hydrophilic
      model drug for in situ encapsulation in PNIPAM/PEO blend nanofibrous scaffolds.
      The rate of drug release can be controlled by adjusting the weight ratio of
      PNIPAM/PEO, the temperature of release medium and the drug loading amount. It is
      suggested that the blend nanofibrous scaffold could be used as a new thermo
      responsive matrix for the entrapment and controlled release of drugs.

PMID- 21889881
TI  - Galectin-3 and the skin.
AB  - Galectin-3 is highly expressed in epithelial cells including keratinocytes and is
      involved in the pathogenesis of inflammatory skin diseases by affecting the
      functions of immune cells. For example, galectin-3 can contribute to atopic
      dermatitis (AD) by promoting polarization toward a Th2 immune response by
      regulating dendritic cell (DC) and T cell functions. In addition, galectin-3 may
      be involved in the development of contact hypersensitivity by regulating the
      migratory capacity of antigen presenting cells. Galectin-3 may act as a regulator
      of epithelial tumor progression and development through various signaling
      pathways, such as inhibiting keratinocyte apoptosis through regulation of the
      activation status of extracellular signal-regulated kinase (ERK) and activated
      protein kinase B (AKT). Galectin-3 is detected at different stages of melanoma
      development. In contrast, a marked decrease in the expression of galectin-3 is
      observed in non-melanoma skin cancers, such as squamous cell carcinoma (SCC) and
      basal cell carcinoma (BCC). Galectin-3 may play an important role in tumor cell
      growth, apoptosis, cell motility, invasion, and metastasis. Galectin-3 may be a
      novel therapeutic target for a variety of skin diseases.

PMID- 21889884
TI  - Liver X receptor negatively regulates fibroblast growth factor 21 in the fatty
      liver induced by cholesterol-enriched diet.
AB  - Cholesterol homeostasis is regulated by the liver X receptor (LXR) at the
      transcriptional level, but it remains unknown whether LXR can affect expression
      levels of intrahepatic lipolysis related gene. Recent evidence has demonstrated
      that fibroblast growth factor 21 (FGF21) regulates hepatic lipolysis and fatty
      acid utilization. In the present study, we examined the role of LXR in FGF21 gene
      expression associated with regulation of cross-talk signals between cholesterol
      and triglyceride metabolism in the liver. An in vivo cholesterol feeding test
      revealed that intake of excess cholesterol increased cholesterol catabolism
      related gene expression as well as fatty-acid biosynthesis related gene
      expression. Moreover, the accumulated cholesterol suppressed FGF21 and hormone
      sensitive lipase (HSL) gene expression. After 15-day cholesterol feeding, hepatic
      triglyceride concentrations were negatively correlated with expression levels of
      the FGF21 and HSL genes in the liver. An LXR agonist (TO-901317) repressed the
      FGF21 gene expression in mouse primary hepatocytes and HepG2 cells. A promoter
      deletion study and electrophoretic mobility shift assay revealed that the human
      FGF21 promoter has at least one LXR response element located from -37 to -22 bp.
      In summary, LXR represses FGF21 gene expression at the transcription level and
      might suppress lipolysis and lipid utilization to protect the liver from excess
      accumulation of toxic cholesterol.

PMID- 21889885
TI  - Tiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic
      disorders via activation of adiponectin signaling followed by enhancement of
      fatty acid oxidation in liver and skeletal muscle in obese-diabetic mice.
AB  - Tiliroside contained in several dietary plants, such as rose hips, strawberry and
      raspberry, is a glycosidic flavonoid and possesses anti-inflammatory,
      antioxidant, anticarcinogenic and hepatoprotective activities. Recently, it has
      been reported that the administration of tiliroside significantly inhibited body
      weight gain and visceral fat accumulation in normal mice. In this study, we
      evaluated the effects of tiliroside on obesity-induced metabolic disorders in
      obese-diabetic KK-A(y) mice. In KK-A(y) mice, the administration of tiliroside
      (100 mg/kg body weight/day) for 21 days failed to suppress body weight gain and
      visceral fat accumulation. Although tiliroside did not affect oxygen consumption,
      respiratory exchange ratio was significantly decreased in mice treated with
      tiliroside. In the analysis of metabolic characteristics, it was shown that
      plasma insulin, free fatty acid and triglyceride levels were decreased, and
      plasma adiponectin levels were increased in mice administered tiliroside. The
      messenger RNA expression levels of hepatic adiponectin receptor (AdipoR)-1 and
      AdipoR2 and skeletal muscular AdipoR1 were up-regulated by tiliroside treatment.
      Furthermore, it was indicated that tiliroside treatment activated AMP-activated
      protein kinase in both the liver and skeletal muscle and peroxisome proliferator
      activated receptor alpha in the liver. Finally, tiliroside inhibited obesity
      induced hepatic and muscular triglyceride accumulation. These findings suggest
      that tiliroside enhances fatty acid oxidation via the enhancement adiponectin
      signaling associated with the activation of both AMP-activated protein kinase and
      peroxisome proliferator-activated receptor alpha and ameliorates obesity-induced
      metabolic disorders, such as hyperinsulinemia and hyperlipidemia, although it
      does not suppress body weight gain and visceral fat accumulation in obese
      diabetic model mice.

PMID- 21889886
TI  - Association between Omega3 and Omega6 fatty acid intakes and serum inflammatory
      markers in COPD.
AB  - Dietary intake of polyunsaturated fatty acids, including omega-3 and omega-6,
      could modulate chronic obstructive pulmonary disease (COPD) persistent
      inflammation. We aimed to assess the relationship between dietary intake of omega
      3 and omega-6 fatty acids and serum inflammatory markers in COPD. A total of 250
      clinically stable COPD patients were included. Dietary data of the last 2 years
      were assessed using a validated food frequency questionnaire (122 items), which
      provided levels of three omega-3 fatty acids: docosahexaenoic acid,
      eicosapentaenoic acid and alpha-linolenic acid (ALA); and two omega-6 fatty
      acids: linoleic acid and arachidonic acid (AA). Inflammatory markers [C-reactive
      protein (CRP), interleukin (IL)-6, IL-8 and tumor necrosis factor alpha
      (TNFalpha)] were measured in serum. Fatty acids and inflammatory markers were
      dichotomised according to their median values, and their association was assessed
      using multivariate logistic regression. Higher intake of ALA (an anti
      inflammatory omega-3 fatty acid) was associated with lower TNFalpha
      concentrations [adjusted odds ratio (OR)=0.46; P=.049]. Higher AA intake (a
      proinflammatory omega-6 fatty acid) was related to higher IL-6 (OR=1.96; P=.034)
      and CRP (OR=1.95; P=.039) concentrations. Therefore, this study provides the
      first evidence of an association between dietary intake of omega-3 and omega-6
      fatty acids and serum inflammatory markers in COPD patients.

PMID- 21889887
TI  - Low background signal platform for the detection of ATP: when a molecular aptamer
      beacon meets graphene oxide.
AB  - A novel molecular aptamer beacon (MAB) was designed by integrating a single
      labeled hairpin-shaped aptamer and graphene oxide (GO). The hairpin-shaped
      aptamer was constructed with anti-ATP aptamer and another five nucleotides added
      to the 5'-end of the aptamer which are complementary to nucleotides at the 3'-end
      of the aptamer to form a hairpin-shaped probe. This newly designed MAB which acts
      as a low background signal platform was used for the ATP detection based on long
      range resonance energy transfer (LrRET). In the absence of ATP, the adsorption of
      the dye-labeled hairpin-shaped aptamer on GO makes the dyes close proximity to GO
      surface resulting in high efficiency quenching of fluorescence of the dyes.
      Therefore, the fluorescence of the designed MAB is completely quenched by GO, and
      the system shows very low background. Conversely, and very importantly, upon the
      adding of ATP, the quenched fluorescence is recovered significantly, and ATP can
      be detected in a wide range of 5-2500MUM with a detection limit of 2MUM and good
      selectivity. Moreover, when the GO-based MAB was used in cellular ATP assays,
      preeminent fluorescence signals were obtained, thus the platform of GO-based MAB
      could be used to detect ATP in real-world samples.

PMID- 21889888
TI  - Modeling transcriptional networks in Drosophila development at multiple scales.
AB  - Quantitative models of developmental processes can provide insights at multiple
      scales. Ultimately, models may be particularly informative for key questions
      about network level behavior during development such as how does the system
      respond to environmental perturbation, or operate reliably in different genetic
      backgrounds? The transcriptional networks that pattern the Drosophila embryo have
      been the subject of numerous quantitative experimental studies coupled to
      modeling frameworks in recent years. In this review, we describe three studies
      that consider these networks at different levels of molecular detail and
      therefore result in different types of insights. We also discuss other
      developmental transcriptional networks operating in Drosophila, with the goal of
      highlighting what additional insights they may provide.

PMID- 21889890
TI  - Plant Y chromosome degeneration is retarded by haploid purifying selection.
AB  - Sex chromosomes evolved many times independently in many different organisms [1].
      According to the currently accepted model, X and Y chromosomes evolve from a pair
      of autosomes via a series of inversions leading to stepwise expansion of a
      nonrecombining region on the Y chromosome (NRY) and the consequential
      degeneration of genes trapped in the NRY [2]. Our results suggest that plants
      represent an exception to this rule as a result of their unique life-cycle that
      includes alteration of diploid and haploid generations and widespread haploid
      expression of genes in plant gametophytes [3]. Using a new high-throughput
      approach, we identified over 400 new genes expressed from X and Y chromosomes in
      Silene latifolia, a plant that evolved sex chromosomes about 10 million years
      ago. Y-linked genes show faster accumulation of amino-acid replacements and loss
      of expression, compared to X-linked genes. These degenerative processes are
      significantly less pronounced in more constrained genes and genes that are likely
      exposed to haploid-phase selection. This may explain why plants retain hundreds
      of expressed Y-linked genes despite millions of years of Y chromosome
      degeneration, whereas animal Y chromosomes are almost completely degenerate.

PMID- 21889889
TI  - Emerging themes in cryptococcal capsule synthesis.
AB  - Cryptococcus neoformans, a basidiomycete yeast and opportunistic pathogen,
      expends significant biosynthetic effort on construction of a polysaccharide
      capsule with a radius that may be many times that of the cell. Beyond posing a
      stimulating challenge in terms of defining biosynthetic pathways, the capsule is
      required for this yeast to cause fatal disease. This combination has focused the
      attention of researchers on this system. Here we briefly review two aspects of
      the rapidly advancing field of capsule synthesis: the extensive variation that
      occurs in capsule polymers and the regulation of capsule biosynthesis.

PMID- 21889892
TI  - Essence of life: essential genes of minimal genomes.
AB  - Essential genes are absolutely required for cell survival. Determination of the
      universal minimal set of genes needed to sustain life is, therefore, expected to
      contribute greatly to our understanding of life at its simplest level, with
      applications in medicine and synthetic biology. The search for the minimal genome
      has led to the identification of often variable gene sets. We argue here that,
      based on the outcome of these analyses, it is becoming increasingly evident that
      some genes, and the functions encoded by them, are absolutely necessary for the
      survival of any living entity, whereas others can be omitted. We also examine
      ways of determining the minimal genome and discuss possible practical
      applications of a minimal cell.

PMID- 21889893
TI  - What are the factors in risk prediction models for rehospitalisation for adults
      with chronic heart failure?
AB  - BACKGROUND: Risk prediction models can assist in identifying individuals at risk
      of adverse events and also the judicious allocation of scare resources. Our
      objective was to describe risk prediction models for the rehospitalisation of
      individuals with chronic heart failure (CHF) and identify the elements
      contributing to these models. METHODS: The electronic data bases MEDLINE,
      PsychINFO, Ovid Evidence-Based Medicine Reviews and Scopus (1950-2010), were
      searched for studies that describe models to predict all-cause hospital
      readmission for individuals with CHF. Search terms included: patient readmission;
      risk; chronic heart failure, congestive heart failure and heart failure. We
      excluded non-English studies, pediatric studies, and publications without
      original data. RESULTS: Only 1 additional model was identified since the review
      undertaken by Ross and colleagues in 2008. All models were derived from data sets
      collected in the United States and patients were followed from 60 days to 18
      months. The only common predictors of re-hospitalisation in the models identified
      by Ross and colleagues were a history of diabetes mellitus and a history of prior
      hospitalisation. The additional model extends its scope to include the non
      clinical factors of social instability and socioeconomic status as predictors of
      rehospitalisation. CONCLUSIONS: In spite of the burden of hospitalisation in CHF,
      there are limited tools to assist clinicians in assessing risk. Developing risk
      prediction models, based on patient, provider and system characteristics may
      assist in identifying individuals in the community at greatest risk and in need
      of targeted interventions to improve outcomes.

PMID- 21889894
TI  - Heart transplantation in HIV-infected patients: more cases in Europe.

PMID- 21889895
TI  - Will CT ordering practices change if we educate residents about the potential
      effects of radiation exposure? Experience at a large academic medical center.
AB  - RATIONALE AND OBJECTIVES: The aim of this study was to determine if educating
      residents about the potential effects of radiation exposure from computed
      tomographic (CT) imaging alters ordering patterns. This study also explored
      whether referring physicians are interested in radiation education and was an
      initial effort to address their CT ordering behavior. MATERIALS AND METHODS: Two
      to four months after a radiologist's lecture on the potential effects of
      radiation exposure related to CT scans, urology and orthopedic residents were
      surveyed regarding the number and types of CT scans they ordered, the use of
      alternative imaging modalities, and whether they used the lecture information to
      educate patients. RESULTS: Twenty-one resident lecture attendants completed the
      survey. The number of CT scans ordered after the lecture stayed constant for 90%
      (19 of 21) and decreased for 10% (two of 21). The types of CT scans ordered
      changed after the lecture for 14% (three of 21). Thirty-three percent (seven of
      21) reported increases in alternative imaging after the lecture, including 24%
      (five of 21) reporting increases in magnetic resonance imaging and 19% (four of
      21) reporting increases in ultrasound. Patients directed questions about
      radiation exposure to 57% (12 of 21); 38% (eight of 21) used the lecture
      information to educate patients. Referring physicians were interested in the
      topic, and afterward, other physician groups requested radiation education
      lectures. CONCLUSIONS: Most clinicians did not change their CT scan ordering
      after receiving education about radiation from a radiologist. Radiation education
      allowed clinicians to discuss CT benefits and risks with their patients and to
      choose appropriate CT protocols. Referring physician groups are interested in
      this topic, and radiologists should be encouraged to give radiation lectures to
      them.

PMID- 21889896
TI  - Interactive high-resolution computed tomography digital atlas of interstitial
      lung disease.
AB  - High-resolution computed tomography is a necessary tool used in the diagnosis of
      interstitial lung disease. The interpretation of high-resolution computed
      tomography can be difficult given the wide spectrum of imaging appearances within
      the same disease and among different diseases. The authors provide a new
      educational method to learn about the spectrum of idiopathic interstitial lung
      disease through the use of a free online digital atlas and review article. This
      atlas can be downloaded at
      http://www.seattlechildrens.org/radiologyeducation/ILD.

PMID- 21889891
TI  - Preservation of the Y transcriptome in a 10-million-year-old plant sex chromosome
      system.
AB  - Classical genetic studies discovered loss of genes from the ancient sex
      chromosome systems of several animals (genetic degeneration), and complete genome
      sequencing confirms that the heterogametic sex is hemizygous for most sex-linked
      genes. Genetic degeneration is thought to result from the absence of
      recombination between the sex chromosome pair (reviewed by [1]) and is very rapid
      after sex chromosome-autosome fusions in Drosophila [2-4]. Plant sex chromosome
      systems allow study of the time course of degeneration, because they evolved from
      a state wholly without sex chromosomes (rather than after a large genome region
      fused to a preexisting sex chromosome), and, in several taxa, recombination
      stopped very recently. However, despite increasing genetic and physical mapping
      of plant nonrecombining sex-determining regions [5-8], it remains very difficult
      to discover sex-linked genes, and it is unclear whether Y-linked genes are losing
      full function. We therefore developed a high-throughput method using RNA-Seq to
      identify sex linkage in Silene latifolia. Recombination suppression between this
      plant's XY sex chromosome pair started only about 10 million years ago [9]. Our
      approach identifies several hundred new sex-linked genes, and we show that this
      young Y chromosome retains many genes, yet these already have slightly reduced
      gene expression and are accumulating changes likely to reduce protein functions.

PMID- 21889897
TI  - Correlation between Doppler velocities and duplex ultrasound carotid cross
      sectional percent stenosis.
AB  - RATIONALE AND OBJECTIVES: Cross-sectional imaging is being increasingly proposed
      as a suitable tool to characterize carotid plaques. The aim of this work was to
      correlate the Doppler velocity parameters with the cross-sectional percent
      stenosis (CPoS) of internal carotid artery (ICA) and to identify the cutoff
      values of these parameters in five progressive classes of stenosis area severity
      (ie, 40%-49%, 50%-59%, 60%-69%, 70%-79%, 80%-90%). MATERIALS AND METHODS: High
      quality scans from 90 patients (mean age, 74 +/- 9 years) with 43%-90% ICA
      stenosis were analyzed. ICA peak-systolic (PSV) and end-diastolic (EDV)
      velocities were measured at maximum stenosis level. Total ICA area and residual
      lumen (RL) were measured to derive the CPoS. A simple physical model described by
      the equation Velocity = Flow rate/Area was considered. Effectively, the CPoS is
      expected to negatively correlate with the inverse of velocity parameters,
      assuming flow rate to be constant. Multiple stepwise regression analyses were
      used to investigate the relationships between velocity and echographic measures.
      RESULTS: With CPoS as the dependent variable, the first significant regressor was
      the inverse ICA-EDV (r(2) = 0.64; P < .0001) followed by inverse ICA-PSV (r(2) =
      0.43; P < .0001). ICA-EDV mean values throughout five progressive classes of
      stenosis were: 28 cm/second for 40%-49% stenosis, 35 cm/second for 50%-59%, 43
      cm/second for 60%-69%, 69 cm/second for 70%-79%. and 103 cm/second for 80%-90%.
      ICA-PSV mean values were: 97 cm/second for 40%-49%, 110 cm/second for 50%-59%,
      136 cm/second for 60%-69%, 224 cm/second for 70%-79%, and 286 cm/second for 80%
      90%. CONCLUSION: ICA-EDV is the parameter that better correlates with CPoS.
      Nevertheless, ICA-PSV maintained a highly significant correlation with CPoS.
      Moreover, the categorization of Doppler parameters in five progressive classes of
      severity of stenosis could provide physicians with an easily accessible tool in
      clinical practice, complementary to the morphological evaluation of cross
      sectional stenosis.

PMID- 21889898
TI  - Detection of a fatty liver after binge drinking: correlation of MR-spectroscopy,
      DECT, biochemistry and histology in a rat model.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate the
      possibility of detecting a fatty liver after binge drinking in an animal model
      using (1)H magnetic resonance spectroscopy ((1)H-MRS), dual-energy computed
      tomography (DECT), biochemistry, and the gold standard of histology. MATERIALS
      AND METHODS: In 20 inbred female Lewis rats, an alcoholic fatty liver was
      induced; 20 rats served as controls. To simulate binge drinking, each rat was
      given a dose of 9.3 g/kg body weight 50% ethanol twice, with 24 hours between
      applications. Forty-eight hours after the first injection, DECT and (1)H-MRS were
      performed. Fat content as well as triglycerides were also determined
      histologically and biochemically, respectively. To assess specific liver enzymes,
      blood was drawn from the orbital venous plexus. RESULTS: In all 20 animals in the
      experimental group, fatty livers were detected using (1)H-MRS, DECT, and
      biochemical and histologic analysis. The spectroscopic fat/water ratio and the
      biochemical determination were highly correlated (r = 0.892, P < .05). A
      significant correlation was found between (1)H-MRS and histologic analysis (r =
      0.941, P < .001). Also, a positive linear correlation was found between the dual
      energy computed tomographic density of DeltaHU and the biochemical (r = 0.751, P
      < .05) and histologic (r = 0.786, P < .001) analyses. CONCLUSIONS: Quantification
      of hepatic fat content on (1)H-MRS showed high correlation with histologic and
      biochemical steatosis determination. In comparison to DECT, it is more suitable
      to reflect the severity of acute fatty liver.

PMID- 21889899
TI  - Epidermoid cyst of the temporal region.
AB  - Epidermoid cysts are rare, slow-growing, benign, developmental cysts that are
      derived from abnormally situated ectodermal tissue. Epidermoid cysts may grow
      anywhere on the body and about 7% of them are located in the head and neck. In
      literature, very few epidermoid cysts have been reported in the temporal region.
      Histopathologically, they are lined with plain stratified keratin-producing
      squamous epithelium, although in some cases part of the lining is made up of
      mucous secreting and ciliated epithelium. This may suggest an endodermal rather
      than an ectodermal origin. We present and discuss the management of a patient
      presenting a posttraumatic epidermoid cyst of the temporal region.

PMID- 21889900
TI  - [Hypofractionated whole breast irradiation: Pro and cons].
AB  - The continuous increase of breast cancer (BC) incidence, the logistic constraints
      of the protracted standard 5-week radiations regimen have led to test short
      hypofractionated whole breast radiation therapy schemes. Three prospective
      randomized trials and a pilot trial have been published. Large numbers of
      patients were included, with follow-up duration ranging from 5 to 12 years. The
      conclusions of these trials were similar, showing local control and toxicity
      equivalent to those of the standard regimen, and supporting the use of three
      schemes: 42.5 Gy/16 fractions/3 weeks, 40 Gy/15 fractions/3 weeks or 41.6 Gy/13
      fractions/5 weeks. However, the patients in these trials had favourable
      prognostic factors, were treated to the breast only and the boost dose, when
      indicated, was delivered with a standard fractionation. Hypofractionated
      treatment can only be recommended in patients treated to the breast only, without
      nodal involvement, with grade<3 tumours and who are not candidate to
      chemotherapy. If a boost is to be given, a standard fractionation should be used.
      Particular care should be taken to avoid heterogeneities leading to high
      fractional doses to organs at risk (lung and heart).

PMID- 21889901
TI  - [Stereotactic radiotherapy for non-small cell lung cancer: From concept to
      clinical reality. 2011 update].
AB  - Only 60% of patients with early-stage non-small cell lung cancer (NSCLC), a
      priori bearing a favorable prognosis, undergo radical resection because of the
      very frequent co-morbidities occurring in smokers, precluding surgery to be
      safely performed. Stereotactic radiotherapy consists of the use of multiple
      radiation microbeams, allowing high doses of radiation to be delivered to the
      tumour (ranging from 7.5 to 20 Gy per fraction) in a small number of fractions
      (one to eight on average). Several studies with long-term follow-up are now
      available, showing the effectiveness of stereotactic radiotherapy to control
      stage I/II non-small cell lung cancer in medically inoperable patients. Local
      control rates are consistently reported to be above 95% with a median survival of
      34 to 45 months. Because of these excellent results, stereotactic radiation
      therapy is now being evaluated in operable patients in several randomized trials
      with a surgical arm. Ultimately, the efficacy of stereotactic radiotherapy in
      early-stage tumours leads to hypothesize that it may represent an opportunity for
      locally-advanced tumors. The specific toxicities of stereotactic radiotherapy
      mostly correspond to radiation-induced chest wall side effects, especially for
      peripheral tumours. The use of adapted fractionation schemes has made feasible
      the use of stereotactic radiotherapy to treat proximal tumours. Overall, from a
      technical concept to the availability of specific treatment devices and the
      publication of clinical results, stereotactic radiotherapy represents a model of
      implementation in thoracic oncology.

PMID- 21889902
TI  - Molecular control and function of endoreplication in development and physiology.
AB  - Endoreplication, also called endoreduplication, is a cell cycle variant of
      multicellular eukaryotes in which mitosis is skipped and cells repeatedly
      replicate their DNA, resulting in cellular polyploidy. In recent years, research
      results have shed light on the molecular mechanism of endoreplication control,
      but the function of this cell-cycle variant has remained elusive. However, new
      evidence is at last providing insight into the biological relevance of cellular
      polyploidy, demonstrating that endoreplication is essential for developmental
      processes, such as cell fate maintenance, and is a prominent response to
      physiological conditions, such as pathogen attack or DNA damage. Thus,
      endoreplication is being revealed as an important module in plant growth that
      contributes to the robustness of plant life.

PMID- 21889903
TI  - DNA replication and repair bypass machines.
AB  - Maintenance of genetic stability is of crucial importance for any form of life.
      Before cell division in each mammalian cell, the process of DNA replication must
      faithfully duplicate three billion bases with an absolute minimum of mistakes.
      This is complicated by the fact that DNA itself is highly reactive and is
      constantly attacked by endogenous and exogenous factors leading to 50,000-100,000
      different damages in the DNA of human cells every day. In this mini-review we
      will focus on lesion bypass by DNA polymerase machines either in replication or
      repair, with particular focus on the repair of oxidative lesions.

PMID- 21889904
TI  - Composition of prehistoric rock-painting pigments from Egypt (Gilf Kebir area).
AB  - The composition of rock-painting pigments from Egypt (Gilf Kebia area) has been
      analyzed by means of molecular spectroscopy such as Fourier transform infrared
      and micro-Raman spectroscopy and scanning electron microscopy coupled to an
      energy dispersive X-ray spectrometer and X-ray fluorescence analysis. Red and
      yellow pigments were recognized as red and yellow ochre with additional rutile.

PMID- 21889905
TI  - Current management and recommendations for access to antiviral therapy of herpes
      labialis.
AB  - Herpes labialis is a common skin infective condition, worldwide, which is
      primarily caused by HSV-1. Recurrent episodes of herpes labialis, also known as
      cold sores, can be frequent, painful, long-lasting and disfiguring for infected
      patients. At present, there are two types of antivirals for the treatment of
      herpes labialis, topical and oral, which are available over the counter or as
      prescription-only. The aim of antiviral therapy is to block viral replication to
      enable shortening the duration of symptoms and to accelerate healing of the
      lesions associated with herpes labialis. This review examines the evidence for
      the effectiveness of current topical and oral antivirals in the management of
      recurrent episodes of herpes labialis. In most countries, oral antivirals for
      herpes labialis are available as prescription-only. However, in early 2010, the
      oral antiviral famciclovir was reclassified from prescription-only medicine to
      pharmacist-controlled status in New Zealand. The benefits and risks associated
      with moving an antiviral therapy for herpes labialis from prescription-only to
      pharmacist-controlled status are reviewed here, and the implications for
      patients, general physicians and pharmacists are considered.

PMID- 21889906
TI  - Rhabdomyolysis and severe muscular weakness in a traveler diagnosed with Alkhurma
      hemorrhagic fever virus infection.
AB  - Alkhurma hemorrhagic fever virus (AHFV) is a tick-borne flavivirus with high case
      fatality rates, endemic in the Arabian Peninsula. Recently AHFV was detected in
      travelers returning from Egypt suggesting geographical spreading. We also report
      AHFV infection in a traveler ex Egypt, representing atypical symptoms of
      rhabdomyolysis and severe muscular weakness.

PMID- 21889907
TI  - Trends of the internal phthalate exposure of young adults in Germany--follow-up
      of a retrospective human biomonitoring study.
AB  - The exposure of the general population to phthalates is of increasing public
      health concern. Variations in the internal exposure of the population are likely,
      because the amounts, distribution and application characters of the phthalate use
      change over time. Estimating the chronological sequences of the phthalate
      exposure, we performed a retrospective human biomonitoring study by investigating
      the metabolites of the five most prominent phthalates in urine. Therefore, 24h
      urine samples from the German Environmental Specimen Bank (ESB) collected from
      240 subjects (predominantly students, age range 19-29 years, 120 females, 120
      males) in the years 2002, 2004, 2006 and 2008 (60 individuals each), were
      analysed for the concentrations of mono-n-butyl phthalate (MnBP) as metabolite of
      di-n-butyl phthalate (DnBP), mono-iso-butyl phthalate (MiBP) as metabolite of di
      iso-butyl phthalate (DiBP), mono-benzyl phthalate (MBzP) as metabolite of
      butylbenzyl phthalate (BBzP), mono-(2-ethylhexyl) phthalate (MEHP), mono-(2-ethyl
      5-hydroxyhexyl) phthalate (5OH-MEHP), mono-(2-ethyl-5-oxohexyl) phthalate (5oxo
      MEHP), mono-(2-ethyl-5-carboxypentyl) phthalate (5cx-MEPP) and mono-(2
      carboxymethyl hexyl) phthalate (2cx-MMHxP) as metabolites of di(2-ethylhexyl)
      phthalate (DEHP), monohydroxylated (OH-MiNP), monooxidated (oxo-MiNP) and
      monocarboxylated (cx-MiNP) mono-iso-nonylphthalates as metabolites of di-iso
      nonyl phthalates (DiNP). Based on the urinary metabolite excretion, together with
      results of a previous study, which covered the years 1988-2003, we investigated
      the chronological sequences of the phthalate exposure over two decades. In more
      than 98% of the urine samples metabolites of all five phthalates were detectable
      indicating a ubiquitous exposure of people living in Germany to all five
      phthalates throughout the period investigated. The medians in samples from the
      different years investigated are 65.4 (2002), 38.5 (2004), 29.3 (2006) and 19.6
      MUg/l (2008) for MnBP, 31.4 (2002), 25.4 (2004), 31.8 (2006) and 25.5 MUg/l
      (2008) for MiBP, 7.8 (2002), 6.3 (2004), 3.6 (2006) and 3.8 MUg/l (2008) for
      MBzP, 7.0 (2002), 5.6 (2004), 4.1 (2006) and 3.3 MUg/l (2008) for MEHP, 19.6
      (2002), 16.2 (2004), 13.2 (2006) and 9.6 MUg/l (2008) for 5OH-MEHP, 13.9 (2002),
      11.8 (2004), 8.3 (2006) and 6.4 MUg/l (2008) for 5oxo-MEHP, 18.7 (2002), 16.5
      (2004), 13.8 (2006) and 10.2 MUg/l (2008) for 5cx-MEPP, 7.2 (2002), 6.5 (2004),
      5.1 (2006) and 4.6 MUg/l (2008) for 2cx-MMHxP, 3.3 (2002), 2.8 (2004), 3.5 (2006)
      and 3.6 MUg/l (2008) for OH-MiNP, 2.1 (2002), 2.1 (2004), 2.2 (2006) and 2.3
      MUg/l (2008) for oxo-MiNP and 4.1 (2002), 3.2 (2004), 4.1 (2006) and 3.6 MUg/l
      (2008) for cx-MiNP. The investigation of the time series 1988-2008 indicates a
      decrease of the internal exposure to DnBP by the factor of 7-8 and to DEHP and
      BzBP by the factor of 2-3. In contrast, an increase of the internal exposure by
      the factor of 4 was observed for DiNP over the study period. The exposure to DiBP
      was found to be stable. In summary, we found decreases of the internal human
      exposure for legally restricted phthalates whereas the exposure to their
      substitutes increased. Future investigations should verify these trends. This is
      of increasing importance since the European Commission decided to require ban or
      authorization from 1.1.2015 for DEHP, DnBP, DiBP and BzBP according to REACh
      Annex XIV.

PMID- 21889908
TI  - A pitfall in the diagnosis of giant bronchogenic cyst presented as loculated
      pleural effusion.
AB  - Being considered as an uncommon congenital anomaly, pulmonary bronchogenic cyst
      requires surgical treatment due to its rarity and mortality especially in
      complicated forms. In the present paper, we are presenting a case report of a
      giant pulmonary bronchogenic cyst (18 cm * 15 cm * 10 cm) misdiagnosed with
      loculated pleural effusion. Because of unsuccessful treatment of tube
      thoracostomy, the patient was scheduled for left thoracotomy. Later giant
      pulmonary cyst was removed completely without any complications. Histopathology
      studies revealed a giant bronchogenic cyst with abscess formation.

PMID- 21889909
TI  - Culture-negative infective endocarditis of the aortic valve due to Aerococcus
      urinae: a rare aetiology.
AB  - Bacteria of the species Aerococcus urinae are Gram-positive, catalase-negative
      cocci that are arranged in pairs, tetrads, or clusters resembling enterococci or
      staphylococci. They are rare causative agents of infective endocarditis.
      Repetitive urinary tract infections based upon underlying genitourinary tract
      abnormalities could involve these bacteria. Due to their similarity to other Gram
      positive cocci misinterpretation may occur along the line of microbiologic
      differentiation, which could potentially lead to a fatal outcome. We herein
      report on the clinical course of a 68 year-old male patient who in the setting of
      an embolic stroke was initially diagnosed with a culture-negative acute infective
      endocarditis of the aortic valve.

PMID- 21889910
TI  - Pericardial tamponade: a life threatening complication of laparoscopic gastro
      oesophageal surgery.
AB  - Laparoscopic surgical procedures involving the gastro-oesophageal region are
      commonly performed for the management of morbid obesity and refractory gastro
      oesophageal reflux disease (GORD). In general, laparoscopic procedures are
      associated with lower morbidity and mortality in comparison with open techniques.
      This report highlights cases of potentially life threatening, late onset
      pericardial tamponade, occurring in the absence of infection or trauma,
      complicating laparoscopic gastro-oesophageal surgery. Possible mechanisms,
      clinical manifestations, diagnostic investigations and management of pericardial
      tamponade are reviewed.

PMID- 21889911
TI  - Assessment of efficacy of antifungals in experimental models of invasive
      aspergillosis in an era of emerging resistance: the value of real-time
      quantitative PCR.
AB  - Experimental models of invasive aspergillosis (IA) have been used to explore
      pharmacokinetic and pharmacodynamic (PK/PD) properties of antifungal agents.
      Survival is still considered the golden standard effect measure but has the
      disadvantage that a large number of animals are needed to determine the dose
      response relationships and PK/PD of antifungals. The feasibility of using fungal
      load by real-time quantitative PCR (qPCR) as an effect measure has been explored
      recently. The majority of studies reported convincingly demonstrate a larger
      dynamic range for qPCR compared to conventional assays. However interpretation
      and translating the results to guidance in clinical decision making need further
      study. It is expected that the use of qPCR will become the primary outcome
      measure for assessment of PK/PD relationships of antifungals in experimental
      models of IA.

PMID- 21889912
TI  - RAGE against the self.

PMID- 21889913
TI  - Obsessive-compulsive disorder in chronic epilepsy.
AB  - There is a long-recognized association between obsessive-compulsive disorder
      (OCD) and chronic epilepsy, most notably refractory temporal lobe epilepsy (TLE).
      The literature documents this association with case reports, patient series, and
      some larger controlled studies that reveal that almost a quarter of patients with
      TLE exhibit OCD features, which may go unrecognized. Obsession features with
      ordering, symmetry, exactness, handwashing, and religiosity occur more often in
      persons with right- or left-sided epileptic foci than in those with idiopathic
      generalized epilepsies or controls. Neurobiological and social factors suggest
      abnormalities of the frontal-thalamic-pallidal-striatal-anterior cingulate
      frontal circuits stemming from the observation that certain diseases, damage, or
      surgery along these circuits may produce or, conversely, reduce OCD in TLE. This
      review explores the literature on case reports, case series, and larger
      retrospective controlled studies and looks at the associations of epilepsy with
      OCD. Contemporary speculation on the theoretical neurobiological underpinnings
      provides some basis on how and where to direct treatment. Invasive deep brain
      stimulation has triggered recent controversy on newer treatment modalities.

PMID- 21889914
TI  - Insular lateralization in tinnitus distress.
AB  - Tinnitus affects 15% of the population. Of these 1-2% are severely disabled by
      it. The role of the autonomic system in tinnitus is hardly being investigated.
      The aim of this study is to investigate the relationship between tinnitus
      distress and lateralization of the anterior insula, known to be involved in
      interoceptive awareness and (para)sympathetic changes. For this, Tinnitus
      Questionnaire scores are correlated to Heart Rate Variability markers, and
      related to neural activity in left and right anterior insula. Our results show
      that tinnitus distress is related to sympathetic activation, in part mediated via
      the right anterior insula.

PMID- 21889915
TI  - Modulation of the processive abasic site lyase activity of a pyrimidine dimer
      glycosylase.
AB  - The repair of cis-syn cyclobutane pyrimidine dimers (CPDs) can be initiated via
      the base excision repair (BER) pathway, utilizing pyrimidine dimer-specific DNA
      glycosylase/lyase enzymes (pdgs). However, prior to incision at lesion sites,
      these enzymes bind to non-damaged DNAs through charge-charge interactions.
      Following initial binding to DNA containing multiple lesions, the enzyme incises
      at most of these sites prior to dissociation. If a subset of these lesions are in
      close proximity, clustered breaks may be produced that could lead to decreased
      cell viability or increased mutagenesis. Based on the co-crystal structures of
      bacteriophage T4-pdg and homology modeling of a related enzyme from Paramecium
      bursaria Chlorella virus-1, the structure-function basis for the processive
      incision activity for both enzymes was investigated using site-directed
      mutagenesis. An assay was developed that quantitatively measured the rates of
      incision by these enzymes at clustered apurinic/apyrimidinic (AP) sites.
      Mathematical modeling of random (distributive) versus processive incisions
      predicted major differences in the rate and extent of the accumulation of singly
      nicked DNAs between these two mechanisms. Comparisons of these models with
      biochemical nicking data revealed significant changes in the damage search
      mechanisms between wild-type pdgs and most of the mutant enzymes. Several
      conserved arginine residues were shown to be critical for the processivity of the
      incision activity, without interfering with catalysis at AP sites. Comparable
      results were measured for incision at clustered CPD sites in plasmid DNAs. These
      data reveal that pdgs can be rationally engineered to retain full catalytic
      activity, while dramatically altering mechanisms of target site location.

PMID- 21889916
TI  - PCNA ubiquitination-independent activation of polymerase eta during somatic
      hypermutation and DNA damage tolerance.
AB  - The generation of high affinity antibodies in B cells critically depends on
      translesion synthesis (TLS) polymerases that introduce mutations into
      immunoglobulin genes during somatic hypermutation (SHM). The majority of
      mutations at A/T base pairs during SHM require ubiquitination of PCNA at lysine
      164 (PCNA-Ub), which activates TLS polymerases. By comparing the mutation spectra
      in B cells of WT, TLS polymerase eta (Poleta)-deficient, PCNA(K164R)-mutant, and
      PCNA(K164R);Poleta double-mutant mice, we now find that most PCNA-Ub-independent
      A/T mutagenesis during SHM is mediated by Poleta. In addition, upon exposure to
      various DNA damaging agents, PCNA(K164R) mutant cells display strongly impaired
      recruitment of TLS polymerases, reduced daughter strand maturation and
      hypersensitivity. Interestingly, compared to the single mutants,
      PCNA(K164R);Poleta double-mutant cells are dramatically delayed in S phase
      progression and far more prone to cell death following UV exposure. Taken
      together, these data support the existence of PCNA ubiquitination-dependent and 
      independent activation pathways of Poleta during SHM and DNA damage tolerance.

PMID- 21889917
TI  - Plastic surgeons: are we dextrous or sinister?

PMID- 21889918
TI  - Interpreting lineage markers in view of subpopulation effects.
AB  - The interpretation of lineage markers is usually carried out as a count in a
      database. The count is a factual statement and does not take into account
      subpopulation effects that may be acting on the data. Subpopulation effects are
      usually taken into consideration for autosomal DNA genotype interpretation by the
      incorporation of a correction, theta. The question has arisen as to whether
      lineage markers should also have such a correction. This paper discusses if and
      how subpopulation effects could be considered.

PMID- 21889919
TI  - Components anteversion in primary cementless THA using straight stem and
      hemispherical cup: a prospective study in 91 hips using CT-scan measurements.
AB  - BACKGROUND: The recommended range of anteversion of the components in total hip
      arthroplasty (THA) is between 10 and 30 degrees , but the intraoperative
      estimation of these versions may be inadequate. HYPOTHESIS: The components
      anteversion in primary cementless THA using straight stem and hemispherical cup
      is not significantly different from the native anteversion of the hip joint.
      OBJECTIVES: To evaluate in a prospective manner the range of anteversion
      currently achieved in cementless THA. PATIENTS AND METHODS: Five senior surgeons
      operated 91 patients with primary cementless THA. We used a straight press fit
      stem and a hemispherical press fit cup. We aimed to obtain femoral anteversion of
      10 to 30 degrees , acetabular anteversion of 10 to 30 degrees  and a global
      combined anteversion of 25 to 55 degrees . Cup position was checked with an
      impactor-positioner, and stem position was determined with the knee flexed 90
      degrees . In all cases we used elevated liners and 28 mm diameter ceramic heads.
      At 3 months postoperatively the component versions were measured using a General
      Electric LightSpeed Pro 16 (Milwaukee, Wi, USA) with the patient in supine
      position. RESULTS: Femoral component measurements ranged from 17 degrees  of
      retroversion to 60 degrees  of anteversion with a mean of 23.0+/-11.8 degrees .
      Similarly, acetabular component version ranged from 28 degrees  of retroversion
      to 46 degrees  of anteversion with a mean of 18.5+/-13.7 degrees . There were no
      correlations to the native femoral and acetabular versions. Only 55 hips (60.4%)
      were within the accepted range of 25 to 55 degrees  of combined anteversion, but
      none of the cases dislocated during a follow-up of 2 years. CONCLUSION: In
      cementless THA with our operative technique, the intraoperative estimation of
      femoral and acetabular anteversion, in many cases, resulted to be inadequate in
      relation to the intended range of 10 to 30 degrees  of anteversion.

PMID- 21889920
TI  - Frequent low expression of chromatin remodeling gene ARID1A in breast cancer and
      its clinical significance.
AB  - BACKGROUND: ARID1A gene encodes BAF250a which is a member of the ARID family of
      DNA-binding proteins and a subunit of human SWI/SNF-related complexes. Low
      expression of ARID1A has been correlated with specific tumor cell lines or
      specific pathological types of cancer tissue. The purpose of this study was to
      investigate the expression of ARID1A in invasive ductal breast carcinomas and to
      evaluate its clinicopathological characteristics and prognostic value. METHODS:
      ARID1A mRNA expression was evaluated by real-time reverse transcriptase
      polymerase chain reaction (RT-PCR) in 40 pairs of fresh frozen breast cancer and
      normal breast samples. BAF250a expression was evaluated by immunohistochemistry
      in 112 paraffin-embedded surgical specimens of invasive breast cancers and 20
      cases of matched normal breast tissues. We further analyzed the
      clinicopathological characteristics of ARID1A expression. Overall survival time
      was assessed by the Kaplan-Meier method and Cox regression model. RESULTS: ARID1A
      mRNA expression was lower in breast cancer tissue than in corresponding normal
      tissue (P<0.001), and this decreased expression level was markedly associated
      with factors such as larger tumor size (P=0.038), higher stage (P=0.016), ER(-)
      (P=0.038), higher Ki-67 (P=0.025), P53 mutation (P=0.018) and ER(-)/PR(-)/Her-2(
      ) molecular subtype (P=0.044). With immunohistochemical staining, we showed that
      low BAF250a expression existed in 56% (63/112) of the breast cancers tissues. Low
      BAF250a expression was significantly associated with tumor stage (P=0.021), P53
      (P=0.018), Ki-67 (P=0.031) and ER(-)/PR(-)/Her-2(-) molecular subtype (P=0.044).
      Low ARID1A expression was a predictor, not an independent, of overall survival.
      CONCLUSION: These data suggest that low ARID1A expression is frequent in breast
      cancers, and we need to investigate further the role of ARID1A and SWI/SNF
      complexes in breast tumorigenesis, especially in triple-negative breast cancer.

PMID- 21889921
TI  - What you should know before your surgical residency, but were afraid to ask.

PMID- 21889922
TI  - Primary peritonitis due to Streptococcus A: laparoscopic treatment.
AB  - Primary peritonitis is defined as peritoneal infection without an evident
      intraperitoneal septic focus. This is a rare condition and few cases are reported
      in the literature. We report a case of primary peritonitis in a 23-year-old
      female that was diagnosed and treated laparoscopically. The challenge for the
      surgeon is to consider the possibility of this diagnosis, and to avoid conversion
      to laparotomy in search of a hypothetical septic focus when none is apparent on
      laparoscopy.

PMID- 21889923
TI  - Long-term expansion of epithelial organoids from human colon, adenoma,
      adenocarcinoma, and Barrett's epithelium.
AB  - BACKGROUND & AIMS: We previously established long-term culture conditions under
      which single crypts or stem cells derived from mouse small intestine expand over
      long periods. The expanding crypts undergo multiple crypt fission events,
      simultaneously generating villus-like epithelial domains that contain all
      differentiated types of cells. We have adapted the culture conditions to grow
      similar epithelial organoids from mouse colon and human small intestine and
      colon. METHODS: Based on the mouse small intestinal culture system, we optimized
      the mouse and human colon culture systems. RESULTS: Addition of Wnt3A to the
      combination of growth factors applied to mouse colon crypts allowed them to
      expand indefinitely. Addition of nicotinamide, along with a small molecule
      inhibitor of Alk and an inhibitor of p38, were required for long-term culture of
      human small intestine and colon tissues. The culture system also allowed growth
      of mouse Apc-deficient adenomas, human colorectal cancer cells, and human
      metaplastic epithelia from regions of Barrett's esophagus. CONCLUSIONS: We
      developed a technology that can be used to study infected, inflammatory, or
      neoplastic tissues from the human gastrointestinal tract. These tools might have
      applications in regenerative biology through ex vivo expansion of the intestinal
      epithelia. Studies of these cultures indicate that there is no inherent
      restriction in the replicative potential of adult stem cells (or a Hayflick
      limit) ex vivo.

PMID- 21889924
TI  - Core-shell biodegradable nanoassemblies for the passive targeting of docetaxel:
      features, antiproliferative activity and in vivo toxicity.
AB  - Amphiphilic block copolymers of poly(E-caprolactone) and poly(ethylene oxide)
      were assembled in core-shell nanoparticles (NPs) by a melting-sonication
      technique (MeSo). The entrapment of the poorly water-soluble anticancer drug
      docetaxel (DTX), nanocarrier cytotoxicity toward different cells and toxicity in
      mice were investigated. The encapsulation mechanism was rationalized and related
      to copolymer properties such as crystallinity and drug solubility in the
      copolymer phase. DTX release from NPs occurred in 2 drug pulses over 30 days. DTX
      entrapment in NPs strongly decreased haemolysis of erythrocytes in comparison
      with a commercial DTX formulation. In comparison with free DTX, NPs were both
      more efficient in inhibiting cell growth of breast and prostate cancer cells and
      less toxic in experimental animal models. The results of this study indicate that
      MeSo is an interesting technique for the achievement of peculiar core-shell
      nanocarriers for the passive targeting and sustained release of poorly water
      soluble anticancer drugs. FROM THE CLINICAL EDITOR: In this study, stealth
      nanoparticles of PEO/PCL block copolymers for passive targeting of docetaxel to
      solid tumors were developed using a novel technique. The studied properties of
      NPs suggest strong potential as anticancer drug-delivery system.

PMID- 21889925
TI  - Self-assembled, cation-selective ion channels from an oligo(ethylene glycol)
      derivative of benzothiazole aniline.
AB  - This paper describes the spontaneous formation of well-defined pores in planar
      lipid bilayers from the self-assembly of a small synthetic molecule that contains
      a benzothiazole aniline (BTA) group attached to a tetra-ethylene glycol (EG4)
      moiety. Macroscopic and single-channel current recordings suggest that these
      pores are formed by the assembly of four BTA-EG4 monomers with an open pore
      diameter that appears similar to the one of gramicidin pores (~0.4 nm). The
      single-channel conductance of these pores is modulated by the pH of the
      electrolyte and has a minimum at pH~3. Self-assembled pores from BTA-EG4 are
      selective for monovalent cations and have long open channel lifetimes on the
      order of seconds. BTA-EG4 monomers in these pores appear to be arranged
      symmetrically across both leaflets of the bilayer, and spectroscopy studies
      suggest that the fluorescent BTA group is localized inside the lipid bilayers. In
      terms of biological activity, BTA-EG4 molecules inhibited growth of gram-positive
      Bacillus subtilis bacteria (IC50~50 MUM) and human neuroblastoma SH-SY5Y cells
      (IC50~60 MUM), while they were not toxic to gram-negative Escherichia coli
      bacteria at a concentration up to 500 MUM. Based on these properties, this drug
      like, synthetic, pore-forming molecule with a molecular weight below 500 g mol(
      1) might be appealing as a starting material for development of antibiotics or
      membrane-permeating moieties for drug delivery. From a biophysical point of view,
      long-lived, well-defined ion-selective pores from BTA-EG4 molecules offer an
      example of a self-assembled synthetic supramolecule with biological function.

PMID- 21889926
TI  - Unresolved mysteries in the biogenesis of mitochondrial membrane proteins.
AB  - Mitochondria are essential eukaryotic organelles that are surrounded by two
      membranes. Both membranes contain a variety of different integral membrane
      proteins. After three decades of research on mitochondrial biogenesis five major
      import complexes with more than 40 subunits altogether were identified and
      characterized. In the current contribution we want to draw attention to some
      unexplored issues regarding the integration of mitochondrial membrane proteins
      and to formulate crucial questions that remain unanswered. This article is part
      of a Special Issue entitled: Protein Folding in Membranes.

PMID- 21889927
TI  - M2, a novel anthracenedione, elicits a potent DNA damage response that can be
      subverted through checkpoint kinase inhibition to generate mitotic catastrophe.
AB  - Pixantrone is a promising anti-cancer aza-anthracenedione that has prompted the
      development of new anthracenediones incorporating symmetrical side-chains of
      increasing length varying from two to five methylene units in each pair of drug
      side-chains. A striking relationship has emerged in which anthracenedione-induced
      growth inhibition and apoptosis was inversely associated with side-chain length,
      a relationship that was attributable to a differential ability to stabilise the
      topoisomerase II (TOP2) cleavage complex. Processing of the complex to a DNA
      double strand break (DSB) flanked by gammaH2AX in nuclear foci is likely to
      occur, as the generation of the primary lesion was antecedent to gammaH2AX
      induction. M2, bearing the shortest pair of side-chains, induced TOP2-mediated
      DSBs efficiently and activated cell cycle checkpoints via Chk1 and Chk2
      phosphorylation, implicating the involvement of ATM and ATR, and induced a
      protracted S phase and subsequent G2/M arrest. The inactive analogue M5,
      containing the longest pair of side-chains, only weakly stimulated any of these
      responses, suggesting that efficient stabilisation of the TOP2 cleavage complex
      was crucial for eliciting a strong DNA damage response (DDR). An M2 induced DDR
      in p53-defective MDA-MB-231 cells was abrogated by UCN-01, a ubiquitous inhibitor
      of kinases including Chk1, in a response associated with substantial mitotic
      catastrophe and strong synergy. The rational selection of checkpoint kinase
      inhibitors may significantly enhance the therapeutic benefit of anthracenediones
      that efficiently stabilise the TOP2 cleavage complex.

PMID- 21889928
TI  - Increased apoptotic efficacy of lonidamine plus arsenic trioxide combination in
      human leukemia cells. Reactive oxygen species generation and defensive protein
      kinase (MEK/ERK, Akt/mTOR) modulation.
AB  - Lonidamine is a safe, clinically useful anti-tumor drug, but its efficacy is
      generally low when used in monotherapy. We here demonstrate that lonidamine
      efficaciously cooperates with the anti-leukemic agent arsenic trioxide (ATO,
      Trisenox) to induce apoptosis in HL-60 and other human leukemia cell lines, with
      low toxicity in non-tumor peripheral blood lymphocytes. Apoptosis induction by
      lonidamine/ATO involves mitochondrial dysfunction, as indicated by early
      mitochondrial permeability transition pore opening and late mitochondrial
      transmembrane potential dissipation, as well as activation of the intrinsic
      apoptotic pathway, as indicated by Bcl-X(L) and Mcl-1 down-regulation, Bax
      translocation to mitochondria, cytochrome c and Omi/HtrA2 release to the cytosol,
      XIAP down-regulation, and caspase-9 and -3 cleavage/activation, with secondary
      (Bcl-2-inhibitable) activation of the caspase-8/Bid axis. Lonidamine stimulates
      reactive oxygen species production, and lonidamine/ATO toxicity is attenuated by
      antioxidants. Lonidamine/ATO stimulates JNK phosphorylation/activation, and
      apoptosis is attenuated by the JNK inhibitor SP600125. In addition, lonidamine
      elicits ERK and Akt/mTOR pathway activation, as indicated by increased ERK, Akt,
      p70S6K and rpS6 phosphorylation, and these effects are reduced by co-treatment
      with ATO. Importantly, co-treatment with MEK/ERK inhibitor (U0126) and PI3K/Akt
      (LY294002) or mTOR (rapamycin) inhibitors, instead of ATO, also potentiates
      lonidamine-provoked apoptosis. These results indicate that: (i) lonidamine
      efficacy is restrained by drug-provoked activation of MEK/ERK and Akt/mTOR
      defensive pathways, which therefore represent potential therapeutic targets. (ii)
      Co-treatment with ATO efficaciously potentiates lonidamine toxicity via defensive
      pathway inhibition and JNK activation. And (iii) conversely, the pro-oxidant
      action of lonidamine potentiates the apoptotic efficacy of ATO as an anti
      leukemic agent.

PMID- 21889929
TI  - Different types of storage devices for blood transportation in the anti-doping
      field.

PMID- 21889930
TI  - Changes in serum obestatin, preptin and ghrelins in patients with Gestational
      Diabetes Mellitus.
AB  - OBJECTIVES: The present study aims to establish the levels of acylated ghrelin,
      desacylated ghrelin, obestatin and preptin, during pregnancy and the postpartum
      period in pregnant women with Gestational Diabetes Mellitus (GDM) and healthy
      pregnancy women. DESIGN AND METHODS: The study registered 20 pregnant women with
      GDM and 20 healthy pregnant women. Fasting venous blood samples were collected
      from all cases between weeks 24 and 28 of pregnancy and after 24h postpartum.
      Hormones were analyzed using ELISA method. RESULTS: Serum acylated ghrelin
      (p:0.001), desacylated ghrelin (p:0.001), obestatin (p:0.006) and preptin
      (p:0.001) levels were all found statistically higher in both groups during the
      postpartum period, when compared to the pregnancy period. A positive correlation
      was established between desacylated ghrelin and acylated ghrelin (p:0.008),
      desacylated ghrelin and preptin (p:0.012) and preptin and insulin (p:0.039) in
      the GDM group during pregnancy. CONCLUSIONS: The studied hormones (especially
      desacylated ghrelin and obestatin) are critical in GDM pathophysiology based on
      the comparison of measure after and before the delivery.

PMID- 21889931
TI  - Prooxidant-anti-oxidant balance is not associated with extent of coronary artery
      disease.
AB  - OBJECTIVE: We have measured the pro-oxidant-antioxidant-balance (PAB) levels in
      patients with defined coronary artery disease (CAD) and compared them with
      concentrations in healthy subjects. DESIGN AND METHODS: Based on angiography
      results, 400 patients with stable CAD were divided into CAD- and CAD+, this being
      further subcategorized into groups with single-, double- and triple-vessel
      disease (VD). RESULTS: The mean PAB values in the healthy subjects, was
      significantly lower than for other groups (P<0.001). In CAD- patients, PAB levels
      were 123.2 +/- 43.9, which was not statistically different compared to groups
      with SVD, 2VD and 3VD (P>0.05). In the CAD+ group, PAB values in 1VD, 2VD and 3VD
      were not significantly different among patients with SVD, 2VD and 3VD (P>0.05).
      CONCLUSIONS: In conclusion, we found higher levels of oxidative stress in CAD+
      patients compared to healthy subjects. The oxidation level was not related to
      measures of the extent of CAD such as number of stenosed vessels.

PMID- 21889932
TI  - Glycerol as a reference material for fecal fat quantitation using low-resolution
      time domain 1H NMR spectroscopy.
AB  - OBJECTIVES: To assess glycerol as reference material for low-resolution time
      domain (1)H NMR analysis of fecal fat. DESIGN AND METHODS: NMR analysis of fecal
      fat in stool samples with added glycerol was used to assess linearity, recovery,
      and relationship with NMR lipid signal. RESULTS: The study revealed for added
      glycerol excellent linearity (r=0.9998), recovery (101-104%), and linear
      relationship with simulated fecal fat content. CONCLUSIONS: Glycerol is an
      effective reference material for NMR fecal fat analysis.

PMID- 21889933
TI  - High Resolution Melting Analysis (HRMA) for the identification of a rare UGT1A1
      promoter polymorphism.

PMID- 21889934
TI  - Evaluation of an ELISA assay for total proinsulin and establishment of reference
      values during an oral glucose tolerance test in a healthy population.
AB  - OBJECTIVES: Assessment of the analytical performance of the Total Proinsulin
      ELISA Kit (Millipore) and determination of reference values. DESIGN AND METHODS:
      Imprecision, specificity, antibodies interference and reference values in
      normoglycaemic non-obese adults were determined. RESULTS: The inter-assay CV is
      <6.9%, the limits of detection and quantification are 0.2 and 0.6 pmol/L. Molar
      cross-reactivity of split proinsulins varies from 103 to 92.5%. The interference
      of anti-(pro)insulin antibodies can be eliminated with the use of polyethylene
      glycol. The reference values are 2.7-14.2 pmol/L at fasting, 8.5-56.5 pmol/L at
      T30 min and 11.9-70.5 pmol/L at T120 min during an OGTT. CONCLUSION: The
      reference values established for this kit, which showed good analytical
      performances, allow for a better assessment of pathologies associated with
      increased proinsulinaemia.

PMID- 21889935
TI  - The gap junctional protein INX-14 functions in oocyte precursors to promote C.
      elegans sperm guidance.
AB  - Innexins are the subunits of invertebrate gap junctions. Here we show that the
      innexin INX-14 promotes sperm guidance to the fertilization site in the
      Caenorhabditis elegans hermaphrodite reproductive tract. inx-14 loss causes cell
      nonautonomous defects in sperm migration velocity and directional velocity.
      Results from genetic and immunocytochemical analyses provide strong evidence that
      INX-14 acts in transcriptionally active oocyte precursors in the distal gonad,
      not in transcriptionally inactive oocytes that synthesize prostaglandin sperm
      attracting cues. Somatic gonadal sheath cell interaction is necessary for INX-14
      function, likely via INX-8 and INX-9 expressed in sheath cells. However, electron
      microscopy has not identified gap junctions in oocyte precursors, suggesting that
      INX-14 acts in a channel-independent manner or INX-14 channels are difficult to
      document. INX-14 promotes prostaglandin signaling to sperm at a step after F
      series prostaglandin synthesis in oocytes. Taken together, our results support
      the model that INX-14 functions in a somatic gonad/germ cell signaling mechanism
      essential for sperm function. We propose that this mechanism regulates the
      transcription of a factor(s) that modulates prostaglandin metabolism, transport,
      or activity in the reproductive tract.

PMID- 21889936
TI  - The FGD homologue EXC-5 regulates apical trafficking in C. elegans tubules.
AB  - Maintenance of the shape of biological tubules is critical for development and
      physiology of metazoan organisms. Loss of function of the Caenorhabditis elegans
      FGD protein EXC-5 allows large fluid-filled cysts to form in the lumen of the
      single-cell excretory canal tubules, while overexpression of exc-5 causes defects
      at the tubule's basolateral surface. We have examined the effects of altering
      expression levels of exc-5 on the distribution of fluorescently-marked
      subcellular organelles. In exc-5 mutants, early endosomes build up in the cell,
      especially in areas close to cysts, while recycling endosomes are depleted.
      Endosome morphology changes prior to cyst formation. Conversely, when exc-5 is
      overexpressed, recycling endosomes are enriched. Since FGD proteins activate the
      small GTPases CDC42 and Rac, these results support the hypothesis that EXC-5 acts
      through small GTPases to move material from apical early endosomes to recycling
      endosomes, and that loss of such movement is likely the cause of tubule
      deformation both in nematodes and in tissues affected by FGD dysfunction such as
      Charcot-Marie-Tooth Syndrome type 4H.

PMID- 21889937
TI  - SoxE gene duplication and development of the lamprey branchial skeleton: Insights
      into development and evolution of the neural crest.
AB  - SoxE genes are multifunctional transcriptional regulators that play key roles in
      specification and differentiation of neural crest. Three members (Sox8, Sox9,
      Sox10) are expressed in the neural crest and are thought to modulate the
      expression and activity of each other. In addition to regulating the expression
      of other early neural crest marker genes, SoxE genes are required for development
      of cartilage. Here we investigated the role of SoxE genes in development of the
      neural crest-derived branchial skeleton in the sea lamprey. Using a morpholino
      knockdown approach, we show that all three SoxE genes described in lamprey are
      required for branchial basket development. Our results suggest that SoxE1 and
      SoxE2 are required for specification of the chondrogenic neural crest. SoxE3
      plays a morphogenetic role in patterning of the branchial basket and may be
      required for the development of mucocartilage, a tissue unique to larval
      lampreys. While the lamprey branchial basket develops primarily from an elastin
      like major extracellular matrix protein that is specific to lampreys, fibrillar
      collagen is also expressed in developing branchial cartilage and may be regulated
      by the lamprey SoxE genes. Our data suggest that the regulation of Type II
      collagen by Sox9 might have been co-opted by the neural crest in development of
      the branchial skeleton following the divergence of agnathan and gnathostome
      vertebrates. Finally, our results also have implications for understanding the
      independent evolution of duplicated SoxE genes among agnathan and gnathostome
      vertebrates.

PMID- 21889938
TI  - Initial diameter of the polar body contractile ring is minimized by the
      centralspindlin complex.
AB  - Polar body formation is an essential step in forming haploid eggs from diploid
      oocytes. This process involves completion of a highly asymmetric cytokinesis that
      results in a large egg and two small polar bodies. Unlike mitotic contractile
      rings, polar body contractile rings assemble over one spindle pole so that the
      spindle must move through the contractile ring before cytokinesis. During time
      lapse imaging of C. elegans meiosis, the contractile ring moved downward along
      the length of the spindle and completed scission at the midpoint of the spindle,
      even when spindle length or rate of ring movement was increased. Patches of
      myosin heavy chain and dynamic furrowing of the plasma membrane over the entire
      embryo suggested that global cortical contraction forces the meiotic spindle and
      overlying membrane out through the contractile ring center. Consistent with this
      model, depletion of myosin phosphatase increased the velocity of ring movement
      along the length of the spindle. Global dynamic furrowing, which was restricted
      to anaphase I and II, was dependent on myosin II, the anaphase promoting complex
      and separase, but did not require cortical contact by the spindle. Large cortical
      patches of myosin during metaphase I and II indicated that myosin was already in
      the active form before activation of separase. To identify the signal at the
      midpoint of the anaphase spindle that induces scission, we depleted two proteins
      that mark the exact midpoint of the spindle during late anaphase, CYK-4 and ZEN
      4. Depletion of either protein resulted in the unexpected phenotype of initial
      ingression of a polar body ring with twice the diameter of wild type. This
      phenotype revealed a novel mechanism for minimizing polar body size. Proteins at
      the spindle midpoint are required for initial ring ingression to occur close to
      the membrane-proximal spindle pole.

PMID- 21889939
TI  - Short-term changes in fathers' hormones during father-child play: impacts of
      paternal attitudes and experience.
AB  - Hormonal differences between fathers and non-fathers may reflect an effect of
      paternal care on hormones. However, few studies have evaluated the hormonal
      responses of fathers after interacting with their offspring. Here we report
      results of a 30-minute in-home experiment in which Filipino fathers played with
      their toddlers and consider whether paternal experience and men's perceptions of
      themselves as fathers affect hormonal changes. Fathers provided saliva and dried
      blood spot samples at baseline (B) and 30 (P30) and 60 (P60, saliva only) minutes
      after the interaction. We tested whether testosterone (T), cortisol (CORT), and
      prolactin (PRL) shifted after the intervention. In the total sample, T did not
      vary over the study period, while CORT declined from B to P30 and P60, and PRL
      also declined from B to P30. Fathers who spent more time in daily caregiving and
      men who thought their spouses evaluated them positively as parental caregivers
      experienced a larger decline in PRL (B to P30) compared to other fathers. First
      time fathers also had larger declines in PRL compared to experienced fathers.
      Experienced fathers also showed a greater decline in CORT (B to P60) compared to
      first-time fathers. These results suggest that males' paternal experience and age
      of offspring affect hormonal responses to father-child play and that there is a
      psychobiological connection between men's perceptions of themselves as fathers
      and their hormonal responsivity to childcare.

PMID- 21889941
TI  - Mineralocorticoid receptors in the medial prefrontal cortex and hippocampus
      mediate rats' unconditioned fear behaviour.
AB  - Corticosterone is released from the adrenal cortex in response to stress, and
      binds to glucocorticosteroid receptors (GRs) and mineralocorticosteroid receptors
      (MRs) in the brain. Areas such as the dorsal hippocampus (DH), ventral
      hippocampus (VH) and medial prefrontal cortex (mPFC) all contain MRs and have
      been previously implicated in fear and/or memory. The purpose of the following
      experiments was to examine the role of these distinct populations of MRs in rats'
      unconditioned fear and fear memory. The MR antagonist (RU28318) was microinfused
      into the DH, VH, or mPFC of rats. Ten minutes later, their unconditioned fear was
      tested in the elevated plus-maze and the shock-probe tests, two behavioral models
      of rat "anxiety." Twenty-four hours later, conditioned fear of a non-electrified
      probe was assessed in rats re-exposed the shock-probe apparatus. Microinfusions
      of RU28318 into each of the three brain areas reduced unconditioned fear in the
      shock-probe burying test, but only microinfusions into the VH reduced
      unconditioned fear in the plus-maze test. RU28318 did not affect conditioned fear
      of the shock-probe 24hr later. MRs in all three areas of the brain mediated
      unconditioned fear to a punctate, painful stimulus (probe shock). However, only
      MRs in the ventral hippocampus seemed to mediate unconditioned fear of the more
      diffuse threat of open spaces (open arms of the plus maze). In spite of the known
      roles of the hippocampus in spatial memory and conditioned fear memory, MRs
      within these sites did not appear to mediate memory of the shock-probe.

PMID- 21889940
TI  - Galanthamine plus estradiol treatment enhances cognitive performance in aged
      ovariectomized rats.
AB  - We hypothesize that beneficial effects of estradiol on cognitive performance
      diminish with age and time following menopause due to a progressive decline in
      basal forebrain cholinergic function. This study tested whether galanthamine, a
      cholinesterase inhibitor used to treat memory impairment associated with
      Alzheimer's disease, could enhance or restore estradiol effects on cognitive
      performance in aged rats that had been ovariectomized in middle-age. Rats were
      ovariectomized at 16-17 months of age. At 21-22 months of age rats began
      receiving daily injections of galanthamine (5mg/day) or vehicle. After one week,
      half of each group also received 17beta-estradiol administered subcutaneously.
      Rats were then trained on a delayed matching to position (DMP) T-maze task,
      followed by an operant stimulus discrimination/reversal learning task. Treatment
      with galanthamine+estradiol significantly enhanced the rate of DMP acquisition
      and improved short-term delay-dependent spatial memory performance. Treatment
      with galanthamine or estradiol alone was without significant effect. Effects were
      task-specific in that galanthamine+estradiol treatment did not significantly
      improve performance on the stimulus discrimination/reversal learning task. In
      fact, estradiol was associated with a significant increase in incorrect responses
      on this task after reversal of the stimulus contingency. In addition, treatments
      did not significantly affect hippocampal choline acetyltransferase activity or
      acetylcholine release. This may be an effect of age, or possibly is related to
      compensatory changes associated with long-term cholinesterase inhibitor
      treatment. The data suggest that treating with a cholinesterase inhibitor can
      enhance the effects of estradiol on acquisition of a DMP task by old rats
      following a long period of hormone deprivation. This could be of particular
      benefit to older women who have not used hormone therapy for many years and are
      beginning to show signs of mild cognitive impairment. Potential mechanisms for
      these effects are discussed.

PMID- 21889942
TI  - Influence of obesity and metabolic dysfunction on the endothelial control in the
      coronary circulation.
AB  - Diseases of the coronary circulation remain the leading cause of death in Western
      society despite impressive advances in diagnosis, pharmacotherapy and post-event
      management. Part of this statistic likely stems from a parallel increase in the
      prevalence of obesity and metabolic dysfunction, both significant risk factors
      for coronary disease. Obesity and diabetes pose unique challenges for the heart
      and their impact on the coronary vasculature remains incompletely understood. The
      vascular endothelium is a major interface between arterial function and the
      physical and chemical components of blood flow. Proper function of the
      endothelium is necessary to preserve hemostasis, maintain vascular tone and limit
      the extent of vascular diseases such as atherosclerosis. Given its central role
      in vascular health, endothelial dysfunction has been the source of considerable
      research interest in diabetes and obesity. In the current review, we will examine
      the pathologic impact of obesity and diabetes on coronary function and the extent
      to which these two factors impact endothelial function. This article is part of a
      Special Issue entitled "Coronary Blood Flow".

PMID- 21889944
TI  - High fat diet induces central obesity, insulin resistance and microvascular
      dysfunction in hamsters.
AB  - Microvascular dysfunction is an early finding in obesity possibly related to co
      morbidities like diabetes and hypertension. Therefore we have investigated
      changes on microvascular function, body composition, glucose and insulin
      tolerance tests (GTT and ITT) on male hamsters fed either with high fat (HFD,
      n=20) or standard (Control, n=21) diet during 16 weeks. Total body fat and
      protein content were determined by carcass analysis, aorta eNOS and iNOS
      expression by immunoblotting assay and mean blood pressure (MAP) and heart rate
      (HR) by an arterial catheter. Microvascular reactivity in response to
      acetylcholine and sodium nitroprusside, functional capillary density (FCD),
      capillary recruitment induced by a hyperinsulinemic status and macromolecular
      permeability after 30 min ischemia was assessed on either cheek pouch or
      cremaster muscle preparations. Compared to Control, HFD animals have shown
      increased visceral fat (6.0 +/- 0.8 vs. 13.8 +/- 0.6g/100g BW), impaired
      endothelial dependent vasodilatation, decreased FCD (11.3 +/- 1.3 vs. 6.8 +/-
      1.2/field) and capillary recruitment during hyperinsulinemia and increased
      macromolecular permeability after ischemia/reperfusion (86.4 +/- 5.2 vs.105.2 +/-
      5.1 leaks/cm(2)), iNOS expression and insulin resistance. MAP, HR, endothelial
      independent vasodilatation and eNOS expression were not different between groups.
      Our results have shown that HFD elicits an increase on visceral fat deposition,
      microvascular dysfunction and insulin resistance in hamsters.

PMID- 21889943
TI  - Myocardial perfusion and contraction in acute ischemia and chronic ischemic heart
      disease.
AB  - A large body of evidence has demonstrated that there is a close coupling between
      regional myocardial perfusion and contractile function. When ischemia is mild,
      this can result in the development of a new balance between supply and energy
      utilization that allows the heart to adapt for a period of hours over which
      myocardial viability can be maintained, a phenomenon known as "short-term
      hibernation". Upon reperfusion after reversible ischemia, regional myocardial
      function remains depressed. The "stunned myocardium" recovers spontaneously over
      a period of hours to days. The situation in myocardium subjected to chronic
      repetitive ischemia is more complex. Chronic dysfunction can initially reflect
      repetitive stunning with insufficient time for the heart to recover between
      episodes of spontaneous ischemia. As the frequency and/or severity of ischemia
      increases, the heart undergoes a series of adaptations which downregulate
      metabolism to maintain myocyte viability at the expense of contractile function.
      The resulting "hibernating myocardium" develops regional myocyte cellular
      hypertrophy as a compensatory response to ischemia-induced apoptosis along with a
      series of molecular adaptations that while regional, are similar to global
      changes found in advanced heart failure. As a result, flow-function relations
      become independently affected by tissue remodeling and interventions that
      stimulate myocyte regeneration. Similarly, chronic vascular remodeling may alter
      flow regulation in a fashion that increases myocardial vulnerability to ischemia.
      Here we review our current understanding of myocardial flow-function relations
      during acute ischemia in normal myocardium and highlight newly identified
      complexities in their interpretation in viable chronically dysfunctional
      myocardium with myocyte cellular and molecular remodeling. This article is part
      of a Special Issue entitled "Coronary Blood Flow".

PMID- 21889945
TI  - Mutagens interfere with microRNA maturation by inhibiting DICER. An in silico
      biology analysis.
AB  - Exposure to environmental mutagens results in alteration of microRNA expression
      mainly oriented towards down-regulation, as typically observed in cigarette
      smoke. However, the molecular mechanism triggering this event is still unknown.
      To shed light on this issue, we developed an 'in silico' analysis testing 25
      established environmental mutagens (polycyclic aromatic hydrocarbons,
      heterocyclic compounds, nitrosoamines, morpholine, ethylnitrosurea, benzene
      derivatives, hydroxyl amines, alkenes) for their potential to interfere with the
      function of DICER, the enzyme involved in the cytoplasmic phase of microRNA
      maturation. In order to analyse the binding affinity between DICER and each
      mutagen, the three-dimensional bioinformatic structures of DICER-RNase III
      domains and of mutagens have been constructed. The binding affinity of mutagens
      for each DICER's RNase III domain was estimated by calculating the global contact
      energy and the number of intermolecular contacts. These two parameters reflect
      the stability of the DICER-mutagen complexes. All the 25 mutagens tested form
      stable complexes with DICER, 20 of which form a complex with DICER A domain, that
      is more stable than those formed by DICER with its natural substrate, i.e. double
      strand short RNAs. These mutagens are benzo(a)pyrene diol epoxide,
      nitroimidazoles, fluorenes, naphthalene, morpholine, stilbenes, hydroxylamines,
      fecapentenes. In the case of exposure to mutagen mixtures (benzo(a)pyrene
      diolepoxide and 4-acetylaminostilbene), synergistic or less than addictive
      effects occur depending on the docking order of the compounds. A group of 8
      mutagens with the highest ability to interfere with this DICER function, was
      identified by hierarchical cluster analysis. This group included 1-ethyl-1
      nitrosourea and 4-nitrosomorpholine. Herein, presented data support the view that
      mutagens interfere with microRNA maturation by binding DICER. This finding sheds
      light on a new epigenetic mechanism exerted by environmental mutagens in inducing
      cell damage.

PMID- 21889946
TI  - AT cells are not radiosensitive for simple chromosomal exchanges at low dose.
AB  - Cells deficient in ATM (product of the gene that is mutated in ataxia
      telangiectasia patients) or NBS (product of the gene mutated in the Nijmegen
      breakage syndrome) show increased yields of both simple and complex chromosomal
      aberrations after high doses (>0.5Gy) of ionizing radiation (X-rays or gamma
      rays), however less is known on how these cells respond at low dose. Previously
      we had shown that the increased chromosome aberrations in ATM and NBS defective
      lines was due to a significantly larger quadratic dose-response term compared to
      normal fibroblasts for both simple and complex exchanges. The linear dose
      response term for simple exchanges was significantly higher in NBS cells compared
      to wild type cells, but not for AT cells. However, AT cells have a high
      background level of exchanges compared to wild type or NBS cells that confounds
      the understanding of low dose responses. To understand the sensitivity
      differences for high to low doses, chromosomal aberration analysis was first
      performed at low dose-rates (0.5Gy/d), and results provided further evidence for
      the lack of sensitivity for exchanges in AT cells below doses of 1Gy. Normal lung
      fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, showed
      increased numbers of exchanges at a dose of 1Gy and higher, but were similar to
      wild type cells at 0.5Gy or below. These results were confirmed using siRNA
      knockdown of ATM. The present study provides evidence that the increased
      radiation sensitivity of AT cells for chromosomal exchanges found at high dose
      does not occur at low dose.

PMID- 21889948
TI  - Neural correlates of an illusory touch experience investigated with fMRI.
AB  - When asked to judge the presence or absence of near-threshold tactile stimuli,
      participants often report touch experiences when no tactile stimulation has been
      delivered ('false alarms'). The simultaneous presentation of a light flash during
      the stimulation period can increase the frequency of touch reports, both when
      touch is and is not present. Using fMRI, we investigated the BOLD response during
      both light-present and light-absent false alarms, testing predictions concerning
      two possible neural mechanisms underlying these illusory touch experiences:
      activation of a tactile representation in primary somatosensory cortex (SI)
      and/or activation of a tactile representation in late processing areas outside of
      sensory-specific cortex, such as medial prefrontal cortex (MPC). Our behavioural
      results showed that participants made false alarms in light-present and light
      absent trials, both of which activated regions of the medial parietal and medial
      prefrontal cortex including precuneus, posterior cingulate and paracingulate
      cortex, suggesting the same underlying mechanism. However, only a non-significant
      increase in SI activity was measured in response to false alarm vs. correct
      rejection trials. We argue that our results provide evidence for the role of top
      down regions in somatic misperception, consistent with findings from studies in
      humans and non-human primates.

PMID- 21889947
TI  - Neural correlates of contextual cueing are modulated by explicit learning.
AB  - Contextual cueing refers to the facilitated ability to locate a particular visual
      element in a scene due to prior exposure to the same scene. This facilitation is
      thought to reflect implicit learning, as it typically occurs without the
      observer's knowledge that scenes repeat. Unlike most other implicit learning
      effects, contextual cueing can be impaired following damage to the medial
      temporal lobe. Here we investigated neural correlates of contextual cueing and
      explicit scene memory in two participant groups. Only one group was explicitly
      instructed about scene repetition. Participants viewed a sequence of complex
      scenes that depicted a landscape with five abstract geometric objects.
      Superimposed on each object was a letter T or L rotated left or right by 90
      degrees . Participants responded according to the target letter (T) orientation.
      Responses were highly accurate for all scenes. Response speeds were faster for
      repeated versus novel scenes. The magnitude of this contextual cueing did not
      differ between the two groups. Also, in both groups repeated scenes yielded
      reduced hemodynamic activation compared with novel scenes in several regions
      involved in visual perception and attention, and reductions in some of these
      areas were correlated with response-time facilitation. In the group given
      instructions about scene repetition, recognition memory for scenes was superior
      and was accompanied by medial temporal and more anterior activation. Thus,
      strategic factors can promote explicit memorization of visual scene information,
      which appears to engage additional neural processing beyond what is required for
      implicit learning of object configurations and target locations in a scene.

PMID- 21889949
TI  - Enhanced suppression of tumor growth by concomitant treatment of human lung
      cancer cells with suberoylanilide hydroxamic acid and arsenic trioxide.
AB  - The efficacy of arsenic trioxide (ATO) against acute promyelocytic leukemia (APL)
      and relapsed APL has been well documented. ATO may cause DNA damage by generating
      reactive oxygen intermediates. Suberoylanilide hydroxamic acid (SAHA), a histone
      deacetylase inhibitor, modulates gene and protein expression via histone
      dependent or -independent pathways that may result in chromatin decondensation,
      cell cycle arrest, differentiation, and apoptosis. We investigated whether ATO
      and SAHA act synergistically to enhance the death of cancer cells. Our current
      findings showed that combined treatment with ATO and SAHA resulted in enhanced
      suppression of non-small-cell lung carcinoma in vitro in H1299 cells and in vivo
      in a xenograft mouse model. Flow cytometric analysis of annexin V+ cells showed
      that apoptotic cell death was significantly enhanced after combined treatment
      with ATO and SAHA. At the doses used, ATO did not interfere with cell cycle
      progression, but SAHA induced p21 expression and led to G1 arrest. A Comet assay
      demonstrated that ATO, but not SAHA, induced DNA strand breaks in H1299 cells;
      however, co-treatment with SAHA significantly increased ATO-induced DNA damage.
      Moreover, SAHA enhanced acetylation of histone H3 and sensitized genomic DNA to
      DNase I digestion. Our results suggest that SAHA may cause chromatin relaxation
      and increase cellular susceptibility to ATO-induced DNA damage. Combined
      administration of SAHA and ATO may be an effective approach to the treatment of
      lung cancer.

PMID- 21889950
TI  - Identification of aryl hydrocarbon receptor binding targets in mouse hepatic
      tissue treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin.
AB  - Genome-wide, promoter-focused ChIP-chip analysis of hepatic aryl hydrocarbon
      receptor (AHR) binding sites was conducted in 8-week old female C57BL/6 treated
      with 30 MUg/kg/body weight 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 2 h and
      24 h. These studies identified 1642 and 508 AHR-bound regions at 2h and 24h,
      respectively. A total of 430 AHR-bound regions were common between the two time
      points, corresponding to 403 unique genes. Comparison with previous AHR ChIP-chip
      studies in mouse hepatoma cells revealed that only 62 of the putative target
      genes overlapped with the 2 h AHR-bound regions in vivo. Transcription factor
      binding site analysis revealed an over-representation of aryl hydrocarbon
      response elements (AHREs) in AHR-bound regions with 53% (2 h) and 68% (24 h) of
      them containing at least one AHRE. In addition to AHREs, E2f-Myc activator motifs
      previously implicated in AHR function, as well as a number of other motifs,
      including Sp1, nuclear receptor subfamily 2 factor, and early growth response
      factor motifs were also identified. Expression microarray studies identified 133
      unique genes differentially regulated after 4 h treatment with TCDD. Of which, 39
      were identified as AHR-bound genes at 2 h. Ingenuity Pathway Analysis on the 39
      AHR-bound TCDD responsive genes identified potential perturbation in biological
      processes such as lipid metabolism, drug metabolism, and endocrine system
      development as a result of TCDD-mediated AHR activation. Our findings identify
      direct AHR target genes in vivo, highlight in vitro and in vivo differences in
      AHR signaling and show that AHR recruitment does not necessarily result in
      changes in target gene expression.

PMID- 21889951
TI  - Neural effects of acute nicotinic treatment on visual spatial attention in non
      smokers.
AB  - Enhanced cortical cholinergic signaling associated with nicotinic acetylcholine
      receptor (nAChR) stimulation has been linked with pro-cognitive actions in a
      variety of performance domains, including attentional tasks. Improvements in
      stimulus selection with the nAChR agonist nicotine have been reported but its
      effects on visual spatial selective attention are unclear. Employing a double
      blind, placebo-controlled design, this study examined the acute actions of
      nicotine (6 mg) in 24 non-smokers performing a visual search task of spatial
      attention that was probed with behavioral performance measures and the N2pc
      component of the event-related potentials (ERPs), which served as a neural index
      of spatial attentional selection. Nicotine did not affect behavioral performance
      indices. In high symptomatic subjects (as indexed by greater increases in heart
      rate post-administration), nicotine was associated with an N2pc amplitude
      enhancement while in low symptomatic individuals it was associated with an N2pc
      difference amplitude decrease. Nicotine modulation of the ERP marker of spatial
      attentional selection corroborates in general the attentional effects of nAChR
      agonists and extends these properties to include altered selective mechanisms
      during visual spatial processing.

PMID- 21889952
TI  - Overview of glutamatergic neurotransmission in the nervous system.
AB  - This introductory article to the special edition on glutamate neurotransmission
      in neuropsychiatric disorders provides an overview of glutamate neurotransmitter
      system physiology and pharmacology. Glutamate was only relatively recently
      recognized as the major excitatory neurotransmitter in the mammalian brain, in
      part due to its ubiquitous nature and diverse metabolic roles within the CNS. The
      extremely high concentration of glutamate in brain tissue paired with its
      excitotoxic potential requires tight physiological regulation of extracellular
      glutamate levels and receptor signaling in order to assure optimal excitatory
      neurotransmission but limits excitotoxic damage. In order to achieve this high
      level of control, the system has developed a complex physiology with multiple
      regulatory processes modulating glutamate metabolism, release, receptor
      signaling, and uptake. The basic physiology of the various regulatory components
      of the system including the rich receptor pharmacology is briefly reviewed.
      Potential contributions from each of the system's components to the
      pathophysiology of neuropsychiatric illnesses are briefly discussed, as are the
      many new pharmacological targets for drug development provided by the system,
      especially as they pertain to the proceeding preclinical and clinical articles in
      this issue.

PMID- 21889954
TI  - Development of a specific ELISA to measure BACE1 levels in human tissues.
AB  - The aspartyl protease BACE1 is the rate limiting enzyme in the synthesis of
      amyloid beta, which accumulation in the human brain is a hallmark of Alzheimer's
      disease (AD). BACE1 has been proposed as a surrogate marker of AD; however, very
      few BACE1 immunoassays have been reported. In the present study we have screened
      ten BACE1 antibodies by Western blot and several antibody pairs to develop a new
      BACE1 sandwich ELISA procedure. We identified one pair that showed little
      background and good reproducibility. Several dilution buffers and sample
      denaturation methods were tried to partially unfold BACE1 before capture. We
      found that dilution in PBS followed by 10 min incubation at 50 degrees C
      critically improves the performance of the assay. Finally, we successfully
      measured BACE1 levels in a few human brain and platelet lysates as well as in
      plasma and AD CSF. We anticipate that this assay will lay the ground to
      accurately measure BACE1 levels in human tissues, which could facilitate the
      molecular diagnosis of AD in the near future.

PMID- 21889955
TI  - Proliferating culture of aged microglia for the study of neurodegenerative
      diseases.
AB  - Microglial cells' phenotype and function change with aging. Since microglial cell
      impairments that are relevant for neurodegenerative diseases appear to be unique
      to aged individuals, it is important to assess function of aged microglia.
      However, most studies are done with microglia from neonates, mostly due to lack
      of reliable protocols to obtain microglia from adult animals. Here, we present a
      conditioned media-dependent culture system that promotes proliferation of adult
      microglia. We observed that inflammatory activation was increasingly oxidative in
      microglia from aged animals. Also, whereas phagocytosis of Abeta by microglia
      from adult animals was more robust than that of microglia from neonates, the
      induction of phagocytosis by TGFbeta was abolished in aged animals. Our results
      show the importance of using adult animals cells for the study of
      neurodegenerative processes or other diseases associated with aging. The proposed
      culture method is inexpensive and cell yield allows for their assessment by
      functional bioassays and biochemistry.

PMID- 21889953
TI  - Anatomical insights into the interaction of emotion and cognition in the
      prefrontal cortex.
AB  - Psychological research increasingly indicates that emotional processes interact
      with other aspects of cognition. Studies have demonstrated both the ability of
      emotional stimuli to influence a broad range of cognitive operations, and the
      ability of humans to use top-down cognitive control mechanisms to regulate
      emotional responses. Portions of the prefrontal cortex appear to play a
      significant role in these interactions. However, the manner in which these
      interactions are implemented remains only partially elucidated. In the present
      review we describe the anatomical connections between ventral and dorsal
      prefrontal areas as well as their connections with limbic regions. Only a subset
      of prefrontal areas are likely to directly influence amygdalar processing, and as
      such models of prefrontal control of emotions and models of emotional regulation
      should be constrained to plausible pathways of influence. We also focus on how
      the specific pattern of feedforward and feedback connections between these
      regions may dictate the nature of information flow between ventral and dorsal
      prefrontal areas and the amygdala. These patterns of connections are inconsistent
      with several commonly expressed assumptions about the nature of communications
      between emotion and cognition.

PMID- 21889956
TI  - Human telomerase reverse transcriptase-immortalized porcine monomyeloid cell
      lines for the production of porcine reproductive and respiratory syndrome virus.
AB  - Porcine reproductive and respiratory syndrome virus (PRRSV) shows highly
      restricted cell tropism and targets subpopulations of differentiated macrophages
      such as porcine alveolar macrophages (PAM) in the natural host. Although primary
      PAM cells would be ideal for in vitro virus production, they are not only
      difficult and expensive for establishment but cannot be frozen reliably for long
      term storage and use. Apart from PAM cells, African green monkey kidney derived
      Marc-145 cells are used commonly for virus propagation. However, concerns have
      been raised regarding a possible modification of specific epitopes associated
      with virus neutralization because of distinct virus entry between PAM and Marc
      145 cells. In order to overcome these problems, the present study was aimed to
      generate immortalized porcine monocyte/macrophage cell lines and to evaluate
      their potential for PRRSV production. Primary PAM cells were transfected stably
      with the human telomerase reverse transcriptase (hTERT) cDNA by a retrovirus
      vector so that constitutive expression of the hTERT protein allows cells to
      proliferate indefinitely. The newly immortalized PAM clones were shown to exert
      functional telomerase activity, indicating sustained expression of hTERT. In
      addition, telomerase-immortalization of PAMs did not affect expression levels of
      the native CD163 receptor on their surface. It was further demonstrated that
      these continuous PAM cell lines are fully permissive for the efficient growth of
      both type 1 and 2 PRRSV strains. The findings suggest that the hTERT-immortalized
      PAM cell lines can enable us to facilitate the continued use of PAMs for virus
      isolation and production and to provide a promising tool for viral pathogenesis
      and immune function studies.

PMID- 21889957
TI  - Effects of D-cycloserine and midazolam on the expression of the GABA-A alpha-2
      receptor subunits in brain structures of fear conditioned rats.
AB  - The role of the GABA-A alpha-2 receptor subunit in the basolateral amygdala
      (BLA), dentate gyrus of the hippocampus (DG) and prefrontal cortex (M2 area)
      during a fear session (performed one week after the conditioned fear test), was
      studied. We employed a model of high (HR) and low anxiety (LR) rats divided
      according to their conditioned freezing response. Pretreatment of rats with d
      cycloserine immediately before the fear session attenuated fear response in HR
      and LR rats and increased the density of alpha-2 subunits in the BLA, M2 area and
      DG of HR animals. The less potent behavioural influence of midazolam (in HR group
      only) was linked to the increased expression of alpha-2 subunit in M2 area and
      DG. These results support a role of the GABA-A receptor alpha-2 subunit in
      processing of emotional cortico-hippocampal input to the BLA.

PMID- 21889958
TI  - Distinct differentiation of closely related species of Bacillus subtilis group
      with industrial importance.
AB  - PCR amplification of 16S rRNA gene by universal primers followed by restriction
      fragment length polymorphism analysis using RsaI, CfoI and HinfI endonucleases,
      distinctly differentiated closely related Bacillus amyloliquefaciens, Bacillus
      licheniformis and Bacillus pumilus from Bacillus subtilis sensu stricto. This
      simple, economical, rapid and reliable protocol could be an alternative to
      misleading phenotype-based grouping of these closely related species.

PMID- 21889959
TI  - Ethanol interferes with gustatory plasticity in Caenorhabditis elegans.
AB  - Ethanol affects the formation of learning and memory in many species. However,
      the molecular mechanisms underlying the behavioral effects of ethanol are still
      poorly understood. In Caenorhabditis elegans, gustatory plasticity is a simple
      learning paradigm, in which animals after prolonged pre-exposure to a chemo
      attractive salt in the absence of food show chemo-aversion to this salt during
      subsequent chemotaxis test stage. We characterized the effect of ethanol on this
      simple learning model. Our results showed that ethanol administration interfered
      with gustatory plasticity during pre-exposure or test stage in well-fed worms.
      Genetic analysis revealed that one mutant previously implicated involved in acute
      ethanol responses, slo-1, as well as two mutants with defects in serotonin
      synthesis, tph-1 and bas-1, failed to exhibit ethanol interference with gustatory
      plasticity. Furthermore, two metabotropic serotonin receptors, SER-4 and SER-7,
      were found to be involved in ethanol-mediated gustatory plasticity. In addition,
      the tph-1 and ser-4 loci were also involved in ethanol's effect on locomotion
      behavior. These data suggested an essential role of serotonin signaling in
      modulating acute effects of ethanol.

PMID- 21889960
TI  - Induction of virus-specific neutralizing immune response against West Nile and
      Japanese encephalitis viruses by chimeric peptides representing T-helper and B
      cell epitopes.
AB  - West Nile virus (WNV) and Japanese encephalitis virus (JEV), the members of JEV
      serocomplex group are pathogens of global health concern. The co-circulation of
      these viruses poses challenges in effective diagnostics due to antigenic
      similarity between the E-protein of these viruses. The present study aimed to
      design chimeric peptides and study the immune response against the same. B-cell
      epitopes were predicted on structural proteins of WNV and JEV based on
      bioinformatics tools. The peptides representing to these B-cell epitopes were
      synthesized and subjected to ELISA. Two peptides, one each from WNV (named WE147)
      and JEV (named JE40) E-protein, showed virus-specific and strong reactivity to
      the immune mice sera and human clinical samples. The chimeric peptides for WNV
      and JEV were constructed by synthesizing the B-cell epitope of WNV (WE147) or JEV
      (JE40) with T-helper epitope (JM17) separated by diglycine spacer in between. The
      immune response generated against these chimeric peptides was found to be
      specific to the respective B-cell epitopes. The anti-peptide sera showed virus
      specific reactivity in ELISA and in immunofluorescence assay with no cross
      reactivity. Also, the anti-peptide sera could neutralize JE and WN viruses in an
      in vitro virus neutralization assay. The B-cell epitopes identified in the
      present study may be used as diagnostic markers for differentiating between WN
      and JE virus infections. The present study can form a basis for future design of
      vaccines.

PMID- 21889961
TI  - Distinct mutant hepatitis B virus genomes, with alterations in all four open
      reading frames, in a single South African hepatocellular carcinoma patient.
AB  - Sequence variation of hepatitis B virus (HBV) can influence the replication,
      antigen expression and pathogenicity of the virus. We report on the mutational
      analysis of HBV performed in a 28-year-old Black South African female diagnosed
      with HBV-induced hepatocellular carcinoma. Full-genome amplification and DNA
      sequencing of HBV was carried out. Five distinct complete genomic clones were
      described with extensive genomic and intragenic variation. Phylogenetic analysis
      revealed that all five clones belonged to subgenotype A1 and that there were at
      least four virus populations with genomes of different lengths ranging from 3194
      to 3253 base pairs. In this particular patient, four major characteristic
      features, not previously reported to occur simultaneously in HBV isolated from a
      single patient, were observed. Firstly, all the clones harboured a 13 base pair
      deletion and a 45 base pair insertion in the basic core promoter (BCP). Secondly,
      a 37 base pair insertion in the core gene with three adjacent single nucleotide
      deletions were observed. Thirdly, premature S gene stop codons were observed in
      some clones and lastly X gene initiation codon mutations were also observed. The
      complex nature of the mutations in the HBV isolated from this single patient may
      have contributed to the early onset of hepatocarcinogenesis.

PMID- 21889962
TI  - Rana grylio virus as a vector for foreign gene expression in fish cells.
AB  - In the present study, Rana grylio virus (RGV, an iridovirus) thymidine kinase
      (TK) gene and viral envelope protein 53R gene were chosen as targets for foreign
      gene insertion. DeltaTK-RGV and Delta53R-RGV, two recombinant RGV, expressing
      enhanced green fluorescence protein (EGFP) were constructed and analyzed in
      Epithelioma papulosum cyprinid (EPC) cells. The EGFP gene which fused to the
      virus major capsid protein (MCP) promoter p50 was inserted into TK and 53R gene
      loci of RGV, respectively. Cells infected with these two recombinant viruses not
      only displayed plaques, but also emitted strong green fluorescence under
      fluorescence microscope, providing a simple method for selection and purification
      of recombinant viruses. DeltaTK-RGV was purified by seven successive rounds of
      plaque isolation and could be stably propagated in EPC cells. All of the plaques
      produced by the purified recombinant virus emitted green fluorescence. However,
      Delta53R-RGV was hard to be purified even through twenty rounds of plaque
      isolation. The purified recombinant virus DeltaTK-RGV was verified by PCR
      analysis and Western blotting. These results showed EGFP was expressed in DeltaTK
      RGV infected cells. Furthermore, one-step growth curves and electron microscopy
      revealed that infection with recombinant DeltaTK-RGV and wild-type RGV are
      similar. Therefore, RGV was demonstrated could be as a viral vector for foreign
      gene expression in fish cells.

PMID- 21889963
TI  - Novel cell-specific and pH-sensitive non-viral gene carrier system. Preface.

PMID- 21889964
TI  - Antifungal action of human cathelicidin fragment (LL13-37) on Candida albicans.
AB  - Human cathelicidin LL37 and its fragments LL13-37 and LL17-32 exhibited similar
      potencies in inhibiting growth of the yeast Candida albicans. After treatment
      with 0.5 MUM and 5 MUM LL13-37, the hyphae changed from a uniformly thick to an
      increasingly slender appearance, with budding becoming less normal in appearance
      and cell death could be detected. Only the yeast form and no hyphal form could be
      observed following exposure to 50 MUM LL13-37. LL13-37 at a concentration of 5
      MUM was able to permeabilize the membrane of yeast form as well as hyphal form of
      C. albicans since the nuclear stain SYTOX Green was localized in both forms.
      Mycelia treated with LL13-37 stained with SYTOX Green, but did not stain with
      MitoTracker deep red, indicating that the mitochondria were adversely affected by
      LL13-37. Bimane-labeled LL13-37 was able to enter some of the hyphae, but not all
      hyphae were affected, suggesting that LL37 impaired membrane permeability
      characteristics in some of the hyphae. Reactive oxygen species was detectable in
      the yeast form of C. albicans cells after treatment with LL13-37 but not in the
      untreated cells. The results suggest that the increased membrane permeability
      caused by LL13-37 might not be the sole cause of cell death. It might lead to the
      uptake of the peptide, which might have some intracellular targets.

PMID- 21889965
TI  - Novel anti-inflammatory peptides as cosmeceutical peptides.
AB  - Ultraviolet (UV) radiation induced inflammation plays an important role in the
      aging of human skin. Prostaglandin (PG) E(2) is the primary mediator of UVB
      induced photoinflammation. We screened an internal library for dipeptides that
      inhibited UVB induced PGE(2) synthesis but showed no cytotoxicity toward human
      keratinocytes. We identified three highly active inhibitory sequences, LE
      (Leu+Glu), MW (Met+Trp) and MY (Met+Tyr). To evaluate their efficacy in human
      skin, 24 sites of abdomen skin were irradiated with a 308 nm excimer laser (300
      mJ/cm(2)), after which 2% LE, MW, MY or a control were applied to the irradiated
      sites for 24h. The erythema index (EI) was measured before and 24h after
      treatment. The results showed that LE and MW significantly decreased UVB induced
      erythema (p=0.041 and p=0.036, respectively), but ME did not. Overall, LE and MW
      are candidate cosmeceutical peptides that can protect skin from UVB induced
      photoinflammation.

PMID- 21889966
TI  - MBL1 gene in nonhuman primates.
AB  - With the aim of investigating the evolution of MBL1P1 (MBL1) gene, we analyzed
      the MBL1 coding region sequences in several specimens of two species of great
      apes, two species of Hylobatidae, four species of Cercopithecidae, and one
      Platyrrhine species, and in human beings. An indication for a progressive
      silencing of the molecule has been found. We found a ~300 bp insertion in the
      first intron of MBL1 in the Cercopithecidae that could explain the different
      splicing between primates species and possibly why Macaca mulatta is able to
      produce a complete protein, whereas in human beings the protein product is
      truncated. Based on our genetic findings, we could speculate that all the
      Cercopithecidae (presenting the 300-bp insertion) may express MBL1 mature protein
      like the M mulatta, whereas the lesser and great apes, which lack this insertion
      as do human beings, may have only the truncated pseudogene.

PMID- 21889967
TI  - Autoimmune and inflammatory mechanisms of CNS damage.
AB  - Brain morphology and function are susceptible to various psysiological
      influences, including changes in the immune system. Inflammation and autoimmunity
      are two principal immunological responses that can compromise the function of
      multiple organs and tissues, including the central nervous system. The present
      article reviews clinical and experimental evidence pointing to structural brain
      damage induced by chronic autoimmune and/or inflammatory processes. Largely due
      to the vast complexity of neuroendocrine and immune systems, most of the
      principal pathogenic circuits are far from elucidated. In addition to summarizing
      the current knowledge, this article aims to highlight the importance of
      interdisciplinary research and combined efforts of physicians and scientists in
      revealing the intricate links between immunity and mental health.

PMID- 21889968
TI  - Social distance modulates recipient's fairness consideration in the dictator
      game: an ERP study.
AB  - Previous research showed that social distance (e.g., being friends or strangers)
      influences people's fairness consideration and other-regarding behavior. However,
      it is not entirely clear how social distance influences the recipient's
      evaluation of (un)fair behavior. In this study, we let people play a dictator
      game in which they received (un)fair offers from either friends or strangers
      while their brain potentials were recorded. Results showed that the medial
      frontal negativity (MFN), a component associated with the processing of
      expectancy violation, was more negative-going in response to unfair than to fair
      offers from friends whereas it did not show differential responses to offers from
      strangers. The P300 was more positive for fair than for unfair offers
      irrespective of friends or strangers making the offers. These results suggest
      that violation of social norms can be detected at an early stage of evaluative
      processing and that this detection can be modulated by social distance.

PMID- 21889969
TI  - Has dysregulated interleukin-6 gene a role in the development of Alzheimer's
      disease?

PMID- 21889970
TI  - Biomarkers of anhedonic-like behavior, antidepressant drug refraction, and stress
      resilience in a rat model of depression.
AB  - The aim of the present study was to identify potential biomarkers for depression
      in the search for novel disease targets and treatment regimens. Furthermore, the
      study includes a search for biomarkers involved in treatment resistance and
      stress resilience in order to investigate mechanisms underlying antidepressant
      drug refraction and stress-coping strategies. Depression-related transcriptomic
      changes in gene expression profiles were investigated in laser-captured
      microdissected (LCM) rat hippocampal granular cell layers (GCL) using the chronic
      mild stress (CMS) rat model of depression and chronic administration of two
      selective serotonin reuptake inhibitors (SSRIs), escitalopram and sertraline. CMS
      rats were segregated into diverging groups according to behavioral readouts, and
      under stringent constraints, the associated differential gene regulations were
      analyzed. Accordingly, we identified four genes associated with recovery, two
      genes implicated in treatment resistance, and three genes involved in stress
      resilience. The identified genes associated with mechanisms of cellular
      plasticity, including signal transduction, cell proliferation, cell
      differentiation, and synaptic release. Hierarchical clustering analysis confirmed
      the subgroup segregation pattern in the CMS model. Thus antidepressant treatment
      refractors cluster with anhedonic-like rats, and, interestingly, stress-resilient
      rats cluster with rats undergoing antidepressant-mediated recovery from
      anhedonia, suggesting antidepressant mechanisms of action to emulate endogenous
      stress-coping strategies.

PMID- 21889971
TI  - Spinal glycinergic and GABAergic neurons expressing C-fos after capsaicin
      stimulation are increased in rats with contralateral neuropathic pain.
AB  - There is increasing evidence that pain transmission on one side of the body is
      influenced by a painful state on the other side. We have investigated this
      phenomenon by studying the activation pattern (using C-fos labeling) of spinal
      glycinergic and GABAergic (Gly/GABA) neurons after capsaicin injection in the
      ipsilateral hind paw of rats that were preconditioned with an acute or chronic
      pain stimulus in the contralateral hind paw or rats that were not preconditioned
      (control). For this purpose, fluorescent in situ hybridization with GlyT2 and
      GAD67 mRNA probes was combined with fluorescent C-fos immunohistochemistry. Rats
      were preconditioned with acute (capsaicin, Complete Freund's Adjuvant (CFA) 1.5
      h), chronic inflammatory (CFA 20 h and 4 days), neuropathic (spared nerve injury
      (SNI) 2 weeks), or control pain stimuli (saline 20 h and 4 days; sham-SNI 2
      weeks). We found that after capsaicin injection in rats preconditioned with CFA
      inflammation (4 days), sham-SNI or with SNI neuropathic pain, the numbers (27 +/-
      3, 21 +/- 2, and 21 +/- 2, respectively) and percentages (55% +/- 4, 43% +/- 2,
      and 42% +/- 2, respectively) of C-fos activated neurons that were Gly/GABA
      increased significantly as compared with control (10 +/- 1 and 25% +/- 2). The
      increase in the total number of C-fos activated Gly/GABA neurons was present
      primarily in the superficial dorsal horn (laminae I and II; control: 9%; CFA 4
      days: 56%; SNI 2 weeks: 42%). This increase in C-fos activation of Gly/GABA
      neurons occurred without significant changes in the total number of C-fos
      activated neurons, and without any significant changes in the mechanical
      thresholds in the hind paws after capsaicin injection. The results showed that
      one-sided chronic pain, especially inflammation, significantly increases the C
      fos activation pattern of spinal Gly/GABA neurons on the other side of the spinal
      cord. This further underlines the existence of a dynamic interaction between ipsi
      and contralateral spinal neurons in the processing of nociceptive information.

PMID- 21889972
TI  - Decreased pain inhibition in irritable bowel syndrome depends on altered
      descending modulation and higher-order brain processes.
AB  - Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder
      involving abdominal pain and bowel dysfunction. IBS pain symptoms have been
      hypothesized to depend on peripheral and central mechanisms, but the
      pathophysiology is still unclear. The aim of the present study was to assess the
      contribution of cerebral and cerebrospinal processes to pain inhibition deficits
      in IBS. Fourteen female patients with diarrhea-predominant IBS (IBS-D) and 14
      healthy female volunteers were recruited. Acute pain and the nociceptive
      withdrawal reflex (RIII reflex) were evoked by transcutaneous electrical
      stimulation of the right sural nerve with modulation by hetero-segmental counter
      irritation produced by sustained cold pain applied on the left forearm.
      Psychological symptoms were assessed by questionnaires. Shock pain decreased
      significantly during counter-irritation in the controls (P<0.001) but not in IBS
      patients (P=0.52). Similarly, RIII-reflex amplitude declined during counter
      irritation in the controls (P=0.009) but not in IBS patients (P=0.11).
      Furthermore, pain-related anxiety increased during counter-irritation in IBS
      patients (P=0.003) but not in the controls (P=0.74). Interestingly, across all
      subjects, counter-irritation analgesia was positively correlated with RIII-reflex
      inhibition (r=0.39, P=0.04) and negatively with pain-related anxiety (r=-0.61,
      P<0.001). In addition, individual differences in counter-irritation analgesia
      were predicted independently by the modulation of RIII responses (P=0.03) and by
      pain catastrophizing (P=0.01), with the latter mediating the effect of pain
      related anxiety. In conclusion, these results demonstrate that pain inhibition
      deficits in female IBS-D patients depend on two potentially separable mechanisms
      reflecting: (1) altered descending modulation and (2) higher-order brain
      processes underlying regulation of pain and affect.

PMID- 21889973
TI  - Female choice for heterozygous mates changes along successive matings in a
      lizard.
AB  - Female mate choice and female multiple mating are major focuses of studies on
      sexual selection. In a multiple mating context, the benefits of mate choice can
      change along successive matings, and female choice would be expected to change
      accordingly. We investigated sequential female mate choice in the moderately
      polyandrous common lizard (Zootoca vivipara, synonym Lacerta vivipara). Along
      successive mating opportunities, we found that females were relatively
      unselective for the first mate, but accepted males of higher heterozygosity for
      subsequent mating, consistent with the trade-up choice hypothesis. We discuss the
      evidence of trade-up mate choice in squamates and generally trade-up for mate
      heterozygosity in order to motivate new studies to fill gaps on these questions.

PMID- 21889974
TI  - Drying eggs to inhibit bacteria: Incubation during laying in a cavity nesting
      passerine.
AB  - Early incubation has been suggested as a defensive adaptation against potentially
      pathogenic bacteria colonizing avian eggshells in the wild. The inhibitory
      mechanisms underlying this adaptation are poorly understood and only recent
      experimental evidence demonstrates that keeping eggs dry is a proximate mechanism
      for the antimicrobial effects of avian incubation. We estimated partial
      incubation (the bouts of incubation that some birds perform during the egg-laying
      period, days of lay 3-5 in our population) intensity of female pied flycatchers
      breeding in nest-boxes using data loggers that allowed a precise measurement of
      temperature just between the eggs in the nest-cup. We also measured relative
      humidity within the nest-boxes and related it to incubation intensity, showing
      that more intense incubation during laying contributes to drying the air near the
      eggs. We analyzed separately the effects of incubation and of relative humidity
      on loads of three types of culturable bacteria known to be present on eggshells,
      heterotrophic bacteria, Gram-negative enterics and pseudomonads. Our results show
      an association of early incubation with an inhibition of bacterial proliferation
      through a drying effect on eggshells, as we found that incubation intensity was
      negatively and relative humidity positively associated with eggshell bacterial
      loads for heterotrophic bacteria, Gram-negative bacteria and pseudomonads,
      although the significance of these associations varied between bacterial groups.
      These results point to microclimatically driven effects of incubation on
      bacterial proliferation on eggshells during laying in a temperate cavity nesting
      passerine.

PMID- 21889975
TI  - Comparison of the effects of nicotine upon the transcellular electrical
      resistance and sucrose permeability of human ECV304/rat C6 co-cultures and human
      CaCo2 cells.
AB  - It is now well established that nicotine adversely affects the integrity of the
      blood-brain barrier (BBB). In contrast, nicotine has been reported to increase
      the transendothelial electrical resistance (TEER) of CaCo2 colon cancer cells. In
      the present study, the effects of nicotine upon the TEER and sucrose permeability
      of ECV304/C6 co-cultures and, for comparative purposes, CaCo2 cells has been
      investigated. Neither ECV304 nor C6 cells were found to express measurable
      membrane levels of nicotinic acetylcholine receptors, as assessed by [3H]
      epibatidine binding. Nicotine treatment (0.01-1 MUM) for up to 48 h had little or
      no effect upon the TEER or sucrose permeability of either ECV304/C6 co-cultures
      or CaCo2 cells. It is concluded that in contrast to the situation for the BBB,
      ECV304 cells lack nicotinic acetylcholine receptors and the barrier properties of
      ECV304/C6 co-cultures are not affected to any important extent by nicotine. This
      study underlines the conclusions made by other authors that the ECV304/C6 co
      culture system is of limited validity as a model of the BBB.

PMID- 21889976
TI  - Key strongylid nematodes of animals - Impact of next-generation transcriptomics
      on systems biology and biotechnology.
AB  - The advent and integration of high-throughput 'omic technologies (e.g., genomics,
      transcriptomics, proteomics and metabolomics) are becoming instrumental to assist
      fundamental explorations of the systems biology of organisms. In particular,
      these technologies now provide unique opportunities for global, molecular
      investigations of parasites. For example, studies of the transcriptomes (all
      transcripts in an organism, tissue or cell) of different species and/or
      developmental stages of parasitic nematodes provide insights into aspects of gene
      expression, regulation and function, which is a major step to understanding their
      biology. The purpose of this article was to review salient aspects of the
      systematics and biology of selected species of parasitic nematodes (particularly
      key species of the order Strongylida) of socio-economic importance, to describe
      conventional and advanced sequencing technologies and bioinformatic tools for
      large-scale investigations of the transcriptomes of these parasites and to
      highlight the prospects and implications of these explorations for developing
      novel methods of parasite intervention.

PMID- 21889977
TI  - Production of plant proteases in vivo and in vitro--a review.
AB  - In the latest two decades, the interest received by plant proteases has increased
      significantly. Plant enzymes such as proteases are widely used in medicine and
      the food industry. Some proteases, like papain, bromelain and ficin are used in
      various processes such as brewing, meat softening, milk-clotting, cancer
      treatment, digestion and viral disorders. These enzymes can be obtained from
      their natural source or through in vitro cultures, in order to ensure a
      continuous source of plant enzymes. The focus of this review will be the
      production of plant proteases both in vivo and in vitro, with particular emphasis
      on the different types of commercially important plant proteases that have been
      isolated and characterized from naturally grown plants. In vitro approaches for
      the production of these proteases is also explored, focusing on the techniques
      that do not involve genetic transformation of the plants and the attempts that
      have been made in order to enhance the yield of the desired proteases.

PMID- 21889978
TI  - Rate and irregularity of electrical activation during atrial fibrillation affect
      myocardial NGF expression via different signalling routes.
AB  - An irregular ventricular response during atrial fibrillation (AF) has been shown
      to mediate an increase in sympathetic nerve activity in human subjects. The
      molecular mechanisms remain unclear. This study aimed to investigate the impact
      of rate and irregularity on nerve growth factor (NGF) expression in
      cardiomyocytes, since NGF is known to be the main contributor to cardiac
      sympathetic innervation density. Cell cultures of neonatal rat ventricular
      myocytes were electrically stimulated for 48 h with increasing rates (0, 5 and 50
      Hz) and irregularity (standard deviation (SD)=5%, 25% and 50% of mean cycle
      length). Furthermore, we analyzed the calcineurin-NFAT and the endothelin-1
      signalling pathways as possible contributors to NGF regulation during arrhythmic
      stimulation. We found that the increase of NGF expression reached its maximum at
      the irregularity of 25% SD by 5 Hz (NGF: 5 Hz 0% SD=1 vs. 5Hz 25% SD=1.57,
      P<0.05). Specific blockade of the ET-A receptor by BQ123 could abolish this NGF
      increase (NGF: 5 Hz 25% SD+BQ123=0.66, P<0.05). High frequency electrical field
      stimulation (HFES) with 50 Hz decreased the NGF expression in a significant
      manner (NGF: 50Hz=0.55, P<0.05). Inhibition of calcineurin-NFAT signalling with
      cyclosporine-A or 11R-VIVIT abolished the HFES induced NGF down-regulation (NGF:
      50 Hz+CsA=1.14, P<0.05). In summary, this study reveals different signalling
      routes of NGF expression in cardiomyocytes exposed to increasing rates and
      irregularity. Whether this translates into different degrees of NGF expression
      and possibly neural sympathetic growth in various forms of ventricular rate
      control during AF remains to be elucidated in further studies.

PMID- 21889979
TI  - Brief seizures cause dendritic injury.
AB  - Seizures may directly cause brain injury by disrupting the structure and function
      of synapses. Previous studies using in vivo time-lapse imaging have demonstrated
      an acute beading of dendrites and loss of dendritic spines immediately following
      status epilepticus, but the effects of brief seizures and the long-term evolution
      of this dendritic injury are unknown. Here, we examined the effects of seizures
      of varying durations on dendritic structure over several weeks using in vivo
      multiphoton imaging with kainate-induced seizures in mice. The degree of
      dendritic injury was directly dependent on the duration of the seizures, with
      seizures lasting more than 30 min (status epilepticus) resulting in a greater
      than 75% spine loss. However, even brief seizures (<5 min) induced moderate
      dendritic beading and spine loss. The dendritic injury from brief seizures
      usually recovered within 2 weeks, whereas status epilepticus-induced injury only
      partially reversed. These studies demonstrate that seizures of all durations may
      trigger at least transient neuronal injury.

PMID- 21889980
TI  - Genetically encoded redox sensor identifies the role of ROS in degenerative and
      mitochondrial disease pathogenesis.
AB  - Mitochondrial dysfunction plays an important role in the pathogenesis of
      neurodegenerative diseases, numerous other disease states and senescence. The
      ability to monitor reactive oxygen species (ROS) within tissues and over time in
      animal model systems is of significant research value. Recently, redox-sensitive
      fluorescent proteins have been developed. Transgenic flies expressing genetically
      encoded redox-sensitive GFPs (roGFPs) targeted to the mitochondria function as a
      useful in vivo assay of mitochondrial dysfunction and ROS. We have generated
      transgenic flies expressing a mitochondrial-targeted roGFP2, demonstrated its
      responsiveness to redox changes in cultured cells and in vivo and utilized this
      protein to discover elevated ROS as a contributor to pathogenesis in a
      characterized neurodegeneration mutant and in a model of mitochondrial
      encephalomyopathy. These studies identify the role of ROS in pathogenesis
      associated with mitochondrial disease and demonstrate the utility of genetically
      encoded redox sensors in Drosophila.

PMID- 21889981
TI  - Viral-mediated overexpression of mutant huntingtin to model HD in various
      species.
AB  - Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder
      caused by an expansion of CAG repeats in the huntingtin (Htt) gene. Despite
      intensive efforts devoted to investigating the mechanisms of its pathogenesis,
      effective treatments for this devastating disease remain unavailable. The lack of
      suitable models recapitulating the entire spectrum of the degenerative process
      has severely hindered the identification and validation of therapeutic
      strategies. The discovery that the degeneration in HD is caused by a mutation in
      a single gene has offered new opportunities to develop experimental models of HD,
      ranging from in vitro models to transgenic primates. However, recent advances in
      viral-vector technology provide promising alternatives based on the direct
      transfer of genes to selected sub-regions of the brain. Rodent studies have shown
      that overexpression of mutant human Htt in the striatum using adeno-associated
      virus or lentivirus vectors induces progressive neurodegeneration, which
      resembles that seen in HD. This article highlights progress made in modeling HD
      using viral vector gene transfer. We describe data obtained with of this highly
      flexible approach for the targeted overexpression of a disease-causing gene. The
      ability to deliver mutant Htt to specific tissues has opened pathological
      processes to experimental analysis and allowed targeted therapeutic development
      in rodent and primate pre-clinical models.

PMID- 21889983
TI  - Anticholinergics boost the pathological process of neurodegeneration with
      increased inflammation in a tauopathy mouse model.
AB  - Anticholinergics, and drugs with anticholinergic properties, are widely and
      frequently prescribed, especially to the elderly. It is well known that these
      drugs decrease cognitive function and increase the risk of dementia. Although the
      mechanism of anticholinergic drug-induced cognitive impairment has been assumed
      to be functionally reduced acetylcholine (ACh) neurotransmission, some data have
      indicated that anticholinergics might enhance the pathology of Alzheimer's
      disease. In this study, we investigated the pathological effects of
      anticholinergics on neurodegeneration. We chronically administered two
      anticholinergics, trihexyphenidyl (TP) and propiverine (PP) (the latter with less
      central anticholinergic action), to neurodegenerative tauopathy model mice 2 to
      10 months old. Furthermore, because the ACh nervous system regulates both central
      and peripheral inflammation, we administered TP or PP to PS19 mice in which we
      had artificially induced inflammation by lipopolysaccharide injection. Tau
      pathology, synaptic loss, and neurodegeneration in the hippocampal region, as
      well as tau insolubility and phosphorylation, were markedly increased in TP
      treated mice and mildly increased in PP-treated mice. Furthermore,
      immunohistochemical analysis revealed microglial proliferation and activation.
      Moreover, anticholinergics increased interleukin-1beta expression in both the
      spleen and brain of the tauopathy model mice intraperitoneally injected with
      lipopolysaccharide to induce systemic inflammation. Interestingly, these
      alterations were more strongly observed in TP-treated mice than in PP-treated
      mice, consistent with the level of central anticholinergic action.
      Anticholinergic drugs not only impair cognitive function by decreased ACh
      neurotransmission, but also accelerate neurodegeneration by suppressing an ACh
      dependent anti-inflammatory system. Anticholinergics should be less readily
      prescribed to reduce the risk of dementia.

PMID- 21889984
TI  - The modulation of Amyotrophic Lateral Sclerosis risk by ataxin-2 intermediate
      polyglutamine expansions is a specific effect.
AB  - Full expansions of the polyglutamine domain (polyQ>=34) within the polysome
      associated protein ataxin-2 (ATXN2) are the cause of a multi-system
      neurodegenerative disorder, which usually presents as a Spino-Cerebellar Ataxia
      and is therefore known as SCA2, but may rarely manifest as Levodopa-responsive
      Parkinson syndrome or as motor neuron disease. Intermediate expansions
      (27<=polyQ<=33) were reported to modify the risk of Amyotrophic Lateral Sclerosis
      (ALS). We have now tested the reproducibility and the specificity of this
      observation. In 559 independent ALS patients from Central Europe, the association
      of ATXN2 expansions (30<=polyQ<=35) with ALS was highly significant. The study of
      1490 patients with Parkinson's disease (PD) showed an enrichment of ATXN2 alleles
      27/28 in a subgroup with familial cases, but the overall risk of sporadic PD was
      unchanged. No association was found between polyQ expansions in Ataxin-3 (ATXN3)
      and ALS risk. These data indicate a specific interaction between ATXN2 expansions
      and the causes of ALS, possibly through altered RNA-processing as a common
      pathogenic factor.

PMID- 21889982
TI  - Enhanced GABAergic network and receptor function in pediatric cortical dysplasia
      Type IIB compared with Tuberous Sclerosis Complex.
AB  - Tuberous Sclerosis Complex (TSC) and cortical dysplasia Type IIB (CDIIB) share
      histopathologic features that suggest similar epileptogenic mechanisms. This
      study compared the morphological and electrophysiological properties of cortical
      cells in tissue from pediatric TSC (n=20) and CDIIB (n=20) patients using whole
      cell patch clamp recordings and biocytin staining. Cell types were normal
      appearing and dysmorphic-cytomegalic pyramidal neurons, interneurons, and
      giant/balloon cells, including intermediate neuronal-glial cells. In the cortical
      mantle, giant/balloon cells occurred more frequently in TSC than in CDIIB cases,
      whereas cytomegalic pyramidal neurons were found more frequently in CDIIB. Cell
      morphology and membrane properties were similar in TSC and CDIIB cases. Except
      for giant/balloon and intermediate cells, all neuronal cell types fired action
      potentials and displayed spontaneous postsynaptic currents. However, the
      frequency of spontaneous glutamatergic postsynaptic currents in normal pyramidal
      neurons and interneurons was significantly lower in CDIIB compared with TSC cases
      and the GABAergic activity was higher in all neuronal cell types in CDIIB.
      Further, acutely dissociated pyramidal neurons displayed higher sensitivity to
      exogenous application of GABA in CDIIB compared with TSC cases. These results
      indicate that, in spite of similar histopathologic features and basic cell
      membrane properties, TSC and CDIIB display differences in the topography of
      abnormal cells, excitatory and inhibitory synaptic network properties, and
      GABA(A) receptor sensitivity. These differences support the notion that the
      mechanisms of epileptogenesis could differ in patients with TSC and CDIIB.
      Consequently, pharmacologic therapies should take these findings into
      consideration.

PMID- 21889985
TI  - Reprint of: Current strategies for the use of affinity tags and tag removal for
      the purification of recombinant proteins.
AB  - Affinity tags are highly efficient tools for protein purification. They allow the
      purification of virtually any protein without any prior knowledge of its
      biochemical properties. The use of affinity tags has therefore become widespread
      in several areas of research e.g., high throughput expression studies aimed at
      finding a biological function to large numbers of yet uncharacterized proteins.
      In some cases, the presence of the affinity tag in the recombinant protein is
      unwanted or may represent a disadvantage for the projected application of the
      protein, like for clinical use. Therefore, an increasing number of approaches are
      available at present that are designed for the removal of the affinity tag from
      the recombinant protein. Most of these methods employ recombinant endoproteases
      that recognize a specific sequence. These process enzymes can subsequently be
      removed from the process by affinity purification, since they also include a tag.
      Here, a survey of the most common affinity tags and the current methods for tag
      removal is presented, with special emphasis on the removal of N-terminal
      histidine tags using TAGZyme, a system based on exopeptidase cleavage. In the
      quest to reduce the significant costs associated with protein purification at
      large scale, relevant aspects involved in the development of downstream processes
      for pharmaceutical protein production that incorporate a tag removal step are
      also discussed. A comparison of the yield of standard vs. affinity purification
      together with an example of tag removal using TAGZyme is also included.

PMID- 21889987
TI  - Reprint of: A new tagged-TEV protease: Construction, optimisation of production,
      purification and test activity.
AB  - The Tobacco Etch Virus (TEV) protease is frequently used in the cleavage of
      recombinant fusion proteins because of its efficiency and high specificity. In
      this work, we present a new recombinant form of TEV termed Streptag II-TEV for
      high-level production and purification of TEV protease from Escherichia coli and
      compare it to the hexahistidine (6xHis) tagged version of TEV. The effects of
      varying the host strain, the bacterial induction temperature (25, 30 and 37
      degrees C) and the IPTG inducer concentration on production and solubility of the
      two recombinant TEV proteases have been examined. Optimal Streptag II-TEV protein
      expression were obtained in the E. coli KRX strain under an induction temperature
      of 25 degrees C in the presence of IPTG at 0.5mM. In these conditions, soluble
      Streptag II-TEV and 6xHis-TEV proteases accounted for about 25% and 18% of total
      soluble proteins, respectively. About 70% of Streptag II-TEV and 60% of 6xHis-TEV
      were detected in the supernatant. Streptag II-TEV protease purifies to near
      homogeneity (approximately 99%) via a simple, single step Strep-Tactin
      chromatography purification protocol based on the presence of Streptag II. The
      higher production of Streptag II-TEV coupled to its purification and cleavage
      efficiencies make it an attractive alternate to 6xHis-TEV.

PMID- 21889988
TI  - Reprint of: Tagging for Protein Expression.
AB  - Tags are frequently used in the expression of recombinant proteins to improve
      solubility and for affinity purification. A large number of tags have been
      developed for protein production and researchers face a profusion of choices when
      designing expression constructs. Here, we survey common affinity and solubility
      tags, and offer some guidance on their selection and use.

PMID- 21889989
TI  - Reprint of: Current strategies for the use of affinity tags and tag removal for
      the purification of recombinant proteins.
AB  - Affinity tags are highly efficient tools for protein purification. They allow the
      purification of virtually any protein without any prior knowledge of its
      biochemical properties. The use of affinity tags has therefore become widespread
      in several areas of research e.g., high throughput expression studies aimed at
      finding a biological function to large numbers of yet uncharacterized proteins.
      In some cases, the presence of the affinity tag in the recombinant protein is
      unwanted or may represent a disadvantage for the projected application of the
      protein, like for clinical use. Therefore, an increasing number of approaches are
      available at present that are designed for the removal of the affinity tag from
      the recombinant protein. Most of these methods employ recombinant endoproteases
      that recognize a specific sequence. These process enzymes can subsequently be
      removed from the process by affinity purification, since they also include a tag.
      Here, a survey of the most common affinity tags and the current methods for tag
      removal is presented, with special emphasis on the removal of N-terminal
      histidine tags using TAGZyme, a system based on exopeptidase cleavage. In the
      quest to reduce the significant costs associated with protein purification at
      large scale, relevant aspects involved in the development of downstream processes
      for pharmaceutical protein production that incorporate a tag removal step are
      also discussed. A comparison of the yield of standard vs. affinity purification
      together with an example of tag removal using TAGZyme is also included.

PMID- 21889990
TI  - Randomness of resting-state brain oscillations encodes Gray's personality trait.
AB  - Randomness of functional Magnetic Resonance Imaging (fMRI) resting-state time
      series has recently been used as a biomarker for numerous disorders including
      Alzheimer's and Parkinson's disease as well as autism. To date, however, it
      remains unknown whether and to what degree personality traits are associated with
      the randomness of resting-state temporal dynamics. To investigate this question,
      we estimated the Hurst exponent - a measure of the randomness of a time-series -
      during resting-state fMRI in brain areas previously associated with trait
      Impulsivity as defined in Gray's Reinforcement Sensitivity Theory of Personality
      in 15 healthy individuals. The Hurst exponent in the ventral striatum as well as
      in the orbitofrontal cortex (OFC) was significantly associated with the measure
      of Gray's trait Impulsivity. Specifically, more random resting-state neural
      dynamics corresponded to higher Impulsivity scores both in the ventral striatum
      (r(15)=-.71; p=.003) and the OFC (r(15)=-.81; p<.001). In summary, we provide
      evidence for an association between individual differences in Gray's Impulsivity
      and randomness in key areas of the reward system which have previously been
      associated with this personality trait. Based on evidence from fMRI and
      electroencephalographical studies, we suggest that this association might arise
      from resting-state fluctuations constraining task-related neural responsiveness.
      Thereby, we outline a potential mechanism linking randomness of resting-state
      dynamics and personality.

PMID- 21889991
TI  - Does training or deprivation modulate amygdala activation?
AB  - Amygdala involvement in visual emotional processing has been unequivocally
      established, but the amygdala's participation in auditory emotional processing is
      less clear. In a previous functional magnetic resonance imaging study (Klinge et
      al., 2010) we investigated the amygdala's role in auditory emotional processing
      in blind and sighted humans. We observed stronger amygdala responses to auditory
      emotional stimuli in the blind who were also better at discriminating emotional
      stimuli. Importantly, inter-individual differences in this skill correlated with
      amygdala activation. While these data suggested that the amygdala serves the
      dominant sensory modality for emotional perception, we could not rule out
      possible influences of use-dependent training effects. To disambiguate between
      plastic changes due to deprivation or training we now studied professional actors
      who have undergone extensive perceptual and expressive auditory emotional
      trainings but no sensory deprivation. Actors showed emotion discrimination skills
      comparable to those of blind individuals. However, in contrast to blind
      volunteers they lacked increased amygdala activations. Surprisingly, actors
      selectively rated angry stimuli as less intense than control participants,
      paralleled by a down-regulation of amygdala responses via the anterior cingulate
      cortex. Taken together, the data from our two studies suggest that enhanced
      amygdala responses in the blind are mainly due to deprivation-induced plasticity,
      as highly trained actors who possess the same excellent emotion discrimination
      skills as the blind did not show these responses. It is also conceivable that the
      actors' training requires a more professional and controlled dealing with the
      emotional stimuli, resulting in a down-regulation of affective experience and
      accompanying amygdala responses.

PMID- 21889992
TI  - The neural markers of an imminent failure of response inhibition.
AB  - In his novel Ulysses, James Joyce wrote that mistakes are the "...portals of
      discovery". The present study investigated the pre-stimulus oscillatory EEG
      signatures of selective attention and motor preparation that predicted failures
      of overt response inhibition. We employed a trial-by-trial spatial cueing task
      using a go/no-go response paradigm with bilateral target stimuli. Subjects were
      required to covertly attend to the spatial location cued on each trial and
      respond to most of the number targets (go trials) at that location while
      withholding responses for one designated number (no-go trials). We analyzed the
      post-cue/pre-target spectral patterns comparing no-go trials in which a response
      occurred in error (False Alarms, FA) with trials in which participants correctly
      withheld a response (Correct Rejections, CR). We found that cue-induced occipital
      alpha (8-12 Hz) lateralization and inter-frequency anti-correlations between the
      motor beta (18-24 Hz) and pre-frontal theta (3-5 Hz) bands each independently
      predicted subsequent failures of response inhibition. Based on these findings, we
      infer that independent perceptual and motor mechanisms operate in parallel to
      contribute to failures of response inhibition.

PMID- 21889993
TI  - PET imaging predicts future body weight and cocaine preference.
AB  - Deficits in dopamine D2/D3 receptor (D2R/D3R) binding availability using PET
      imaging have been reported in obese humans and rodents. Similar deficits have
      been reported in cocaine-addicts and cocaine-exposed primates. We found that
      D2R/D3R binding availability negatively correlated with measures of body weight
      at the time of scan (ventral striatum), at 1 (ventral striatum) and 2 months
      (dorsal and ventral striatum) post scan in rats. Cocaine preference was
      negatively correlated with D2R/D3R binding availability 2 months (ventral
      striatum) post scan. Our findings suggest that inherent deficits in striatal
      D2R/D3R signaling are related to obesity and drug addiction susceptibility and
      that ventral and dorsal striatum serve dissociable roles in maintaining weight
      gain and cocaine preference. Measuring D2R/D3R binding availability provides a
      way for assessing susceptibility to weight gain and cocaine abuse in rodents and
      given the translational nature of PET imaging, potentially primates and humans.

PMID- 21889994
TI  - Anticorrelations in resting state networks without global signal regression.
AB  - Anticorrelated relationships in spontaneous signal fluctuation have been
      previously observed in resting-state functional magnetic resonance imaging
      (fMRI). In particular, it was proposed that there exists two systems in the brain
      that are intrinsically organized into anticorrelated networks, the default mode
      network, which usually exhibits task-related deactivations, and the task-positive
      network, which usually exhibits task-related activations during tasks that
      demands external attention. However, it is currently under debate whether the
      anticorrelations observed in resting state fMRI were valid or were instead
      artificially introduced by global signal regression, a common preprocessing
      technique to remove physiological and other noise in resting-state fMRI signal.
      We examined positive and negative correlations in resting-state connectivity
      using two different preprocessing methods: a component base noise reduction
      method (CompCor, Behzadi et al., 2007), in which principal components from noise
      regions-of-interest were removed, and the global signal regression method. Robust
      anticorrelations between a default mode network seed region in the medial
      prefrontal cortex and regions of the task-positive network were observed under
      both methods. Specificity of the anticorrelations was similar between the two
      methods. Specificity and sensitivity for positive correlations were higher under
      CompCor compared to the global regression method. Our results suggest that
      anticorrelations observed in resting-state connectivity are not an artifact
      introduced by global signal regression and might have biological origins, and
      that the CompCor method can be used to examine valid anticorrelations during
      rest.

PMID- 21889995
TI  - Asymmetric bias in user guided segmentations of brain structures.
AB  - Brain morphometric studies often incorporate comparative hemispheric asymmetry
      analyses of segmented brain structures. In this work, we present evidence that
      common user guided structural segmentation techniques exhibit strong left-right
      asymmetric biases and thus fundamentally influence any left-right asymmetry
      analyses. In this study, MRI scans from ten pediatric subjects were employed for
      studying segmentations of amygdala, globus pallidus, putamen, caudate, and
      lateral ventricle. Additionally, two pediatric and three adult scans were used
      for studying hippocampus segmentation. Segmentations of the sub-cortical
      structures were performed by skilled raters using standard manual and semi
      automated methods. The left-right mirrored versions of each image were included
      in the data and segmented in a random order to assess potential left-right
      asymmetric bias. Using shape analysis we further assessed whether the asymmetric
      bias is consistent across subjects and raters with the focus on the hippocampus.
      The user guided segmentation techniques on the sub-cortical structures exhibited
      left-right asymmetric volume bias with the hippocampus displaying the most
      significant asymmetry values (p<<0.01). The hippocampal shape analysis revealed
      the bias to be strongest on the lateral side of the body and medial side of the
      head and tail. The origin of this asymmetric bias is considered to be based in
      laterality of visual perception; therefore segmentations with any degree of user
      interaction contain an asymmetric bias. The aim of our study is to raise
      awareness in the neuroimaging community regarding the presence of the asymmetric
      bias and its influence on any left-right hemispheric analyses. We also recommend
      reexamining previous research results in the light of this new finding.

PMID- 21889996
TI  - AFNI: what a long strange trip it's been.
AB  - AFNI is an open source software package for the analysis and display of
      functional MRI data. It originated in 1994 to meet the specific needs of
      researchers at the Medical College of Wisconsin, in particular the mapping of
      activation maps to Talairach-Tournoux space, but has been expanded steadily since
      then into a wide-ranging set of tool for FMRI data analyses. AFNI was the first
      platform for real-time 3D functional activation and registration calculations.
      One of AFNI's main strengths is its flexibility and transparency. In recent
      years, significant efforts have been made to increase the user-friendliness of
      AFNI's FMRI processing stream, with the introduction of "super-scripts" to setup
      the entire analysis, and graphical front-ends for these managers.

PMID- 21889997
TI  - A rapid, semi-automated method for scoring micronuclei in mononucleated mouse
      lymphoma cells.
AB  - A semi-automated scoring system has been developed to provide rapid, accurate
      assessment of micronuclei in preparations of mononuclear mouse lymphoma L5178Y
      cells. Following exposure to a range of test agents, flat, single-cell
      preparations were produced from exponentially growing cultures by
      cytocentrifugation. Following staining with 4'-6-diamidino-2-phenylindole (DAPI),
      cells were scanned by use of the MicroNuc module of Metafer 4 v 3.4.102, after
      modifying the classifier developed for selecting micronuclei in binucleate cells
      to increase its sensitivity. The image gallery of all cells was then sorted to
      bring aberrant cells to the top of the gallery to assess visually the numbers of
      cells with micronuclei, as distinct from other debris. Slide quality was shown to
      be paramount in obtaining accurate results from an automated scan and the data
      obtained compared very well with the incidence of micronuclei scored
      conventionally by microscopy. Compared with manual scoring the time saving is
      considerable, as more than 2000 images are captured in approximately 2min, with
      subsequent visual assessment of aberrant cells in the image gallery taking about
      1-2min/slide. By scanning all aberrant cells, the system also captures additional
      information on necrotic, apoptotic and fragmented cells. Although optimised for
      mouse lymphoma cells, it should be simple to adapt the method for any cell type
      growing in suspension.

PMID- 21889998
TI  - Metabolic and growth inhibitory effects of conjugated fatty acids in the cell
      line HT-29 with special regard to the conversion of t11,t13-CLA.
AB  - Conjugated fatty acids (CFAs) exhibit growth inhibitory effects on colon cancer
      in vitro and in vivo. To investigate whether the anticancerogenic potency depends
      on number or configuration of the conjugated double bonds, the effect of
      conjugated linoleic acid (CLA; C18:2) isomers and conjugated linolenic acid
      (CLnA; C18:3) isomers on viability and growth of HT-29 cells were compared. Low
      concentrations of CLnAs (<10MUM) yielded a higher degree of inhibitory effects
      compared to CLAs (40MUM). All trans-CFAs were more effective compared to
      cis/trans-CFAs as follows: t9,t11,t13-CLnA>=c9,t11,t13-CLnA>t11,t13-CLA>=t9,t11
      CLA>c9,t11-CLA. The mRNA expression analysis of important genes associated with
      fatty acid metabolism showed an absence of ?5-/?6-desaturases and elongases in HT
      29 cells, which was confirmed by fatty acid analysis. Using time- and dose
      dependent stimulation experiments several metabolites were determined. Low
      concentrations of all trans-CFAs (5-20MUM) led to dose-dependent increase of
      conjugated t/t-C16:2 formed by beta-oxidation of C18 CFAs, ranging from 1-5% of
      total FAME. Importantly, it was found that CLnA is converted to CLA and that CLA
      is inter-converted (t11,t13-CLA is metabolized to c9,t11-CLA) by HT-29 cells. In
      summary, our study shows that growth inhibition of human cancer cells is
      associated with a specific cellular transcriptomic and metabolic profile of fatty
      acid metabolism, which might contribute to the diversified ability of CFAs as
      anti-cancer compounds.

PMID- 21889999
TI  - Identification and characterization of ABCB1-mediated and non-apoptotic sebum
      secretion in differentiated hamster sebocytes.
AB  - Sebaceous glands secrete sebum onto the skin surface in a holocrine manner and as
      such a thin lipid layer is formed as a physiological barrier. In the present
      study, extracellular level of triacylglycerols (TG), a major sebum component, as
      well as intracellular TG accumulation was augmented in insulin-differentiated
      hamster sebocytes (DHS). The DHS exhibited phosphatidylserine exposure in an
      apoptosis-independent manner. In addition, intracellular ATP level and membrane
      transporter activity using a substrate, Rhodamine 123, were highly detectable in
      the DHS rather than in the undifferentiated hamster sebocytes. A membrane
      transporter activating reagent, 2'(3')-O-(4-benzoylbenzoyl) adenosine 5'
      triphosphate (BzATP), enhanced transporter activity, extracellular TG level, and
      phosphatidylserine exposure in the DHS. Both transporter activity and TG
      secretion were suppressed by R-verapamil, a potent membrane-transporter
      inhibitor, in the BzATP-treated and untreated DHS. Furthermore, the gene
      expression and production of ATP-binding cassette subfamily B member 1 (ABCB1)
      were augmented in the DHS. ABCB1 was also detectable in sebaceous glands in the
      skin of hamsters. Moreover, the cell-differentiation- and BzATP-augmented
      transporter activity and TG secretion were dose-dependently inhibited by adding
      not only an ABCB1 antibody but also a selective inhibitor of ABCB1, PSC833. Thus,
      these results provide novel evidence that ABCB1 is involved in sebum secretion in
      the DHS, which is associated with non-apoptotic phosphatidylserine exposure and
      the increased level of intracellular ATP. These findings should accelerate the
      understanding of sebum secretion occurring in a holocrine-independent manner in
      sebaceous glands, and may contribute to the development of therapies for
      sebaceous gland disorders such as acne, seborrhea, and xerosis.

PMID- 21890000
TI  - Cholesterol and membrane phospholipid compositions modulate the leakage capacity
      of the swaposin domain from a potato aspartic protease (StAsp-PSI).
AB  - Potato aspartic proteases (StAPs) and their swaposin domain (StAsp-PSI) are
      proteins with cytotoxic activity which involves plasma membrane destabilization.
      The ability of these proteins to produce cell death varies with the cellular
      type. Therefore, StAPs and StAsp-PSI selective cytotoxicity could be attributed
      to the different membrane lipid compositions of target cells. In this work we
      investigate the possible mechanism by which StAPs and StAsp-PSI produce selective
      membrane destabilization. Results obtained from leakage assays show that StAsp
      PSI is a potent inducer of the leakage of LUVs containing anionic phospholipids,
      especially those containing phosphatidylglycerol. Based in these results, we
      suggest that the cytotoxic activity of StAsp-PSI on pathogenic microorganisms
      could be mediated by the attraction between the exposed positive domains of StAsp
      PSI and the negatively charged microorganism membrane. On the other hand, our
      circular dichroism spectroscopic measurements and analysis by size exclusion
      chromatography and followed by electrophoresis, indicate that hydrophobic
      environment is necessary to StAsp-PSI oligomerization and both StAsp-PSI
      disulfide bounds and membrane with negative charged phospholipids are required by
      StAsp-PSI to produce membrane destabilization and then induce cell death in
      tumors and microorganism cell targets. Additionally, we demonstrate that the
      presence of cholesterol into the LUV membranes strongly diminishes the capacity
      of StAsp-PSI to produce leakage. This result suggests that the lack of hemolytic
      and cytotoxic activities on human lymphocytes of StAsp-PSI/StAPs may be partly
      due by the presence of cholesterol in these cell membrane types.

PMID- 21890001
TI  - Dendrobium officinale polysaccharides ameliorate the abnormality of aquaporin 5,
      pro-inflammatory cytokines and inhibit apoptosis in the experimental Sjogren's
      syndrome mice.
AB  - Sjogren's syndrome (SS) is a chronic autoimmune disease with exocrine glands
      disorder. Our previous work demonstrated the protective effect of Dendrobium
      officinale polysaccharides (DP) both on the phenotypes of patients and animal
      model with SS. In this study, we expand these observations to explore the
      possible mechanisms. The experimental SS mice model was established with or
      without the administration of DP (20mg/ml). The time frame of lymphocytes
      infiltration, apoptotic indicators such as Bax, Bcl-2 and caspase-3 were
      determined in submandibular gland (SG), as well as the subsequent mRNA expression
      of cytokines such as TNF-alpha, IL-1 beta and IL-6. The expression and
      localization of aquaporin-5 (AQP-5) was examined by Western blot and
      immunofluorescent staining. As the result, DP could suppress the progressive
      lymphocytes infiltration and apoptosis, and balance the chaos of pro-inflammatory
      cytokines in the SG. Further, DP ameliorated the abnormalities of AQP-5 and
      maintained its functional importance of saliva secretion. In addition, the
      protection of AQP-5 by DP from human TNF-alpha was supported by an in vitro study
      on A-253 cell line. Our study further supported the efficacy of DP as the
      promising candidate for the therapy of SS.

PMID- 21890002
TI  - Protected effect of Esenbeckia leiocarpa upon the inflammatory response induced
      by carrageenan in a murine air pouch model.
AB  - This study was conducted to investigate the anti-inflammatory efficacy of
      Esenbeckia leiocarpa against the inflammation caused by the carrageenan using a
      murine air pouch model. MATERIAL AND METHODS: The effects of the crude
      hydroalcoholic extract (CHE), fractions (n-hexane (Hex) and ethyl acetate
      (AcOEt)), subfractions (polar (Pol) and nonpolar (Nonpol)), or isolated compounds
      (dihydrocorynantheol (DHC) and beta-sitosterol (beta-Sit)) isolated from CHE upon
      leukocytes, exudate, myeloperoxidase (MPO) adenosine-deaminase (ADA),
      nitrate/nitrite (NO(x)), interleukin-1 beta (IL-1beta), tumor necrosis factor
      alpha (TNF-alpha), and inhibitory kappa-B-alpha (IkappaB-alpha) degradation were
      evaluated. The CHE, Alk, Pol, Nonpol, DHC and beta-Sit, inhibited leukocytes,
      exudate, MPO and ADA, NO(x), IL-1beta, and TNF-alpha (P<0.05). The Hex and AcOEt
      fractions inhibited all of the proinflammatory parameters, except the exudate.
      The compound DHC prevented the IkappaB-alpha degradation. CONCLUSION: E.
      leiocarpa possesses important anti-inflammatory properties. These inhibitory
      effects occurred along with the downregulation of nitric oxide, IL-1beta and TNF
      alpha levels. The isolated compounds DHC and beta-Sit may be partially
      responsible for these anti-inflammatory effects.

PMID- 21890003
TI  - Short-term modulation of the exercise ventilatory response in younger and older
      women.
AB  - The exercise ventilatory response (EVR; defined as the slope of the relationship
      between ventilation and CO(2) production) is reversibly augmented within a single
      exercise trial with increased respiratory dead space (DS) in both younger (Wood,
      H.E., Mitchell, G.S., Babb, T.G., 2008. Short-term modulation of the exercise
      ventilatory response in young men. J. Appl. Physiol. 104, 244-252) and older
      (Wood, H.E., Mitchell, G.S., Babb, T.G., 2010. Short-term modulation of the
      exercise ventilatory response in older men. Respir. Physiol. Neurobiol. 173, 37
      46) men. The neural mechanism accounting for this augmentation is known as short
      term modulation (STM) of the EVR. Since the effects of female sex hormones on STM
      are unknown, we examined the capacity for STM in healthy adult women of two age
      groups; nine younger (29+/-3 yrs, eumenorrheic) and seven older (69+/-3 yrs,
      postmenopausal) women were studied at rest and during cycle exercise (10 W, 30 W;
      not randomized) in control conditions and with added external DS (200 mL, 400 mL;
      randomized). Within groups, the main effects of DS and work rate on EVR were
      analyzed with a two-way repeated measures ANOVA; EVR comparisons between groups
      were made with unpaired t-tests. In both groups, EVR increased progressively with
      increasing DS volume (e.g. at 10 W 31+/-4 and 35+/-6 in control, 40+/-11 and 40+/
      6 with 200 mL, 48+/-12 and 49+/-11 with 400 mL DS in younger and older women,
      respectively). In younger women, the effects of DS on EVR differed between work
      rates (significant interaction, p<0.05), although this was not the case for older
      women. In both groups, [Formula: see text] regulation was similar between DS and
      control; hence, increased EVR was not due to altered chemoreceptor feedback from
      rest to exercise. EVR with and without added DS did not differ between age
      groups. We conclude that the capacity for STM of the EVR with added DS is similar
      in healthy younger and older women.

PMID- 21890004
TI  - Kinetic mechanism of an aldehyde reductase of Saccharomyces cerevisiae that
      relieves toxicity of furfural and 5-hydroxymethylfurfural.
AB  - An effective means of relieving the toxicity of furan aldehydes, furfural (FFA)
      and 5-hydroxymethylfurfural (HMF), on fermenting organisms is essential for
      achieving efficient fermentation of lignocellulosic biomass to ethanol and other
      products. Ari1p, an aldehyde reductase from Saccharomyces cerevisiae, has been
      shown to mitigate the toxicity of FFA and HMF by catalyzing the NADPH-dependent
      conversion to corresponding alcohols, furfuryl alcohol (FFOH) and 5
      hydroxymethylfurfuryl alcohol (HMFOH). At pH 7.0 and 25 degrees C, purified Ari1p
      catalyzes the NADPH-dependent reduction of substrates with the following values
      (k(cat) (s(-1)), k(cat)/K(m) (s(-1)mM(-1)), K(m) (mM)): FFA (23.3, 1.82, 12.8),
      HMF (4.08, 0.173, 23.6), and dl-glyceraldehyde (2.40, 0.0650, 37.0). When acting
      on HMF and dl-glyceraldehyde, the enzyme operates through an equilibrium ordered
      kinetic mechanism. In the physiological direction of the reaction, NADPH binds
      first and NADP(+) dissociates from the enzyme last, demonstrated by k(cat) of HMF
      and dl-glyceraldehyde that are independent of [NADPH] and (K(ia)(NADPH)/k(cat))
      that extrapolate to zero at saturating HMF or dl-glyceraldehyde concentration.
      Microscopic kinetic parameters were determined for the HMF reaction (HMF+NADPH<
      >HMFOH+NADP(+)), by applying steady-state, presteady-state, kinetic isotope
      effects, and dynamic modeling methods. Release of products, HMFOH and NADP(+), is
      84% rate limiting to k(cat) in the forward direction. Equilibrium constants,
      [NADP(+)][FFOH]/[NADPH][FFA][H(+)]=5600*10(7)M(-1) and
      [NADP(+)][HMFOH]/[NADPH][HMF][H(+)]=4200*10(7)M(-1), favor the physiological
      direction mirrored by the slowness of hydride transfer in the non-physiological
      direction, NADP(+)-dependent oxidation of alcohols (k(cat) (s(-1)), k(cat)/K(m)
      (s(-1)mM(-1)), K(m) (mM)): FFOH (0.221, 0.00158, 140) and HMFOH (0.0105,
      0.000104, 101).

PMID- 21890005
TI  - A novel halotolerant xylanase from marine isolate Bacillus subtilis cho40: gene
      cloning and sequencing.
AB  - Although several xylanases have been studied, only few xylanases from marine
      micro-organisms have been reported. We report here a novel halotolerant xylanase
      from marine bacterium Bacillus subtilis cho40 isolated from Chorao island of
      mandovi estuary Goa, India. Extracellular xylanase was produced by using
      agricultural residue such as wheat bran as carbon source under solid-state
      fermentation (SSF). The optimal pH and temperature of xylanase were reported to
      be 6.0 and 60 degrees C, respectively. Xyn40 was highly salt-tolerant, and showed
      highest activity at 0.5M NaCl. Xylanase activity was greatly induced (140%) when
      pre-incubated with 0.5M NaCl for 4h. The xylanase gene, xyn40, from marine
      bacterium B. subtilis cho40 was cloned, and expressed in Escherichia coli. The
      xylanase gene was 645 bp long and had a 215 amino acid ORF protein with a
      molecular mass of 22.9 kDa. It had all features of xylanase enzyme and showed
      homology to xylanases reported from B. subtilis. It differs from the earlier
      reported xylanase sequences by the presence of more serine residues compared to
      threonine and also by the presence of polar (hydrophilic) amino acids in higher
      abundance (61%) than non-polar amino acids (39%). The novel xylanase, reported in
      this study is a halotolerant enzyme from marine isolate and can play a very
      important role in bioethanol production from marine seaweeds.

PMID- 21890006
TI  - SILAC zebrafish for quantitative analysis of protein turnover and tissue
      regeneration.
AB  - Defective tissue regeneration is thought to contribute to several human diseases,
      including neurodegenerative disorders, heart failure and various lung diseases.
      Boosting the regenerative capacity has been suggested a possible therapeutic
      approach. Methods to metabolically label newly synthesized proteins in vivo with
      stable isotopic forms of amino acids holds promise for the study of protein
      turnover and tissue regeneration that are fundamental to the sustained life of
      all organisms. Here, we used the "stable isotope labeling with amino acids in
      cell culture" (SILAC) approach to explore normal protein turnover and tissue
      regeneration in adult zebrafish. The ratio of labeled and unlabeled
      proteins/peptides in specific organs of zebrafish fed a SILAC diet containing
      (13)C(6)-labeled lysine was determined by liquid chromatography and tandem mass
      spectrometry. Labeling was highest in tissues with high regenerative capacity,
      including intestine, liver, and fin, whereas brain and heart displayed the lowest
      labeling. Proteins with high degree of labeling were mainly involved in catalytic
      or transport activity pathways. The technique also verified increased protein
      synthesis during regeneration of the caudal fin following amputation. This newly
      developed SILAC zebrafish model constitutes a novel tool to analyze tissue
      regeneration in an animal model amenable to genetic and pharmacologic
      manipulation.

PMID- 21890007
TI  - Effects of Clostridium difficile Toxin A on the proteome of colonocytes studied
      by differential 2D electrophoresis.
AB  - Clostridium difficile is a spore-forming anaerobic pathogen, commonly associated
      with severe diarrhea or life-threatening pseudomembraneous colitis. Its main
      virulence factors are the single-chain, multi-domain toxin A (TcdA) and B (TcdB).
      Their glucosyltransferase domain selectively inactivates Rho proteins leading to
      a reorganization of the cytoskeleton. To study exclusively glucosyltransferase
      dependent molecular effects of TcdA, human colonic cells (Caco-2) were treated
      with recombinant wild type TcdA and the glucosyltransferase deficient variant of
      the toxin, TcdA(gd) for 24h. Changes in the protein pattern of the colonic cells
      were investigated by 2-D DIGE and LCMS/MS methodology combined with detailed
      proteome mapping. gdTcdA did not induce any detectable significant changes in the
      protein pattern. Comparing TcdA-treated cells with a control group revealed seven
      spots of higher and two of lower intensity (p<0.05). Three proteins are involved
      in the assembly of the cytoskeleton (beta-actin, ezrin, and DPYL2) and four are
      involved in metabolism and/or oxidative stress response (ubiquitin, DHE3, MCCB,
      FABPL) and two in regulatory processes (FUBP1, AL1A1). These findings correlate
      well to known effects of TcdA like the reorganization of the cytoskeleton and
      stress the importance of Rho protein glucosylation for the pathogenic effects of
      TcdA.

PMID- 21890008
TI  - Increased callus mass and enhanced strength during fracture healing in mice
      lacking the sclerostin gene.
AB  - Humans with inherited sclerostin deficiency have high bone mass. Targeted
      deletion of the sclerostin gene in mice (SOST-KO) causes increases in bone
      formation, bone mass and bone strength. Inhibition of sclerostin by a monoclonal
      antibody increases bone formation and enhances fracture healing in rodent and
      primate models. In this study, we describe the temporal progression of femoral
      fracture healing in SOST-KO mice compared with wild type (WT) control mice to
      further characterize the role of sclerostin in fracture healing. Sixty-seven male
      9-10 week-old SOST-KO (N=37) and WT (N=30) mice underwent a closed femoral
      fracture. Weekly radiography was used to monitor the progress of healing.
      Histologic sections were used to characterize callus composition, evaluate callus
      bridging, and quantify lamellar bone formation on days 14 and 28. Densitometry
      and biomechanical testing were utilized to characterize bone mass and strength at
      the fractured and contralateral femurs on day 45. A significant improvement in
      time to radiographic healing (no discernible fracture line) was observed in SOST
      KO mice, which corresponded to an increase in histologic bony bridging at 14 days
      (38% versus 0% in WT). Both genotypes appeared to be nearly fully bridged at 28
      days post-fracture. The increased bridging at 14 days was associated with 97%
      greater bone area and 40% lower cartilage area in the callus of SOST-KO mice as
      compared to WT mice. Bone formation-related endpoints were higher in SOST-KO mice
      at both 14 and 28 days. At 45 days post-fracture, peak load and bone mass were
      significantly greater in the fractured femurs of SOST-KO mice as compared to WT
      mice. In conclusion, fractures in mice lacking sclerostin showed accelerated
      bridging, greater callus maturation, and increased bone formation and strength in
      the callus.

PMID- 21890009
TI  - Sclerostin expression is induced by BMPs in human Saos-2 osteosarcoma cells but
      not via direct effects on the sclerostin gene promoter or ECR5 element.
AB  - Sclerostin is a secreted inhibitor of Wnt signaling and plays an essential role
      in the regulation of bone mass. The expression of sclerostin is largely
      restricted to osteocytes although its mode of transcriptional regulation is not
      well understood. We observed regulated expression of sclerostin mRNA and protein
      that was directly correlated with the mineralization response in cultured human
      Saos-2 osteosarcoma cells and rat primary calvarial cells. Sclerostin mRNA and
      protein levels were increased following treatment of cells with BMP2, BMP4 and
      BMP7. Analysis of deletion mutants from the -7.4 kb upstream region of the human
      sclerostin promoter did not reveal any specific regions that were responsive to
      BMPs, Wnt3a, PTH, TGFbeta1 or Activin A in Saos-2 cells. The downstream ECR5
      element did not show enhancer activity in Saos-2 cells and also was not affected
      when Saos-2 cells were treated with BMPs or PTH. Genome-wide microarray analysis
      of Saos-2 cells treated with BMP2 showed significant changes in expression of
      several transcription factors with putative consensus DNA binding sites in the
      region of the sclerostin promoter. However, whereas most factors tested showed
      either a range of inhibitory activity (DLX family, MSX2, HEY1, SMAD6/7) or lack
      of activity on the sclerostin promoter including SMAD9, only MEF2B showed a
      positive effect on both the promoter and ECR5 element. These results suggest that
      the dramatic induction of sclerostin gene expression by BMPs in Saos-2 cells
      occurs indirectly and is associated with late stage differentiation of
      osteoblasts and the mineralization process.

PMID- 21890010
TI  - In vivo validation of a computational bone adaptation model using open-loop
      control and time-lapsed micro-computed tomography.
AB  - Cyclic mechanical loading augments trabecular bone mass, mainly by increasing
      trabecular thickness. For this reason, we hypothesized that an in silico
      thickening algorithm using open-loop control would be sufficient to reliably
      predict the response of trabecular bone to cyclic mechanical loading. This would
      also mean that trabecular bone adaptation could be modeled as a system responding
      to an input signal at the onset of the process in a predefined manner, without
      feedback from the outputs. Here, time-lapsed in vivo micro-computed tomography
      scans of mice cyclically loaded at the sixth caudal vertebra were used to
      validate the in silico model. When comparing in silico and in vivo data sets
      after a period of four weeks, a maximum prediction error of 2.4% in bone volume
      fraction and 5.4% in other bone morphometric indices was calculated.
      Superimposition of sequentially acquired experimental images and simulated
      structures revealed that in silico simulations deposited thin and homogeneous
      layers of bone whilst the experiment was characterized by local areas of strong
      thickening, as well as considerable volumes of bone resorption. From the results,
      we concluded that the proposed computational algorithm predicted changes in bone
      volume fraction and global parameters of bone structure very well over a period
      of four weeks while it was unable to reproduce accurate spatial patterns of local
      bone formation and resorption. This study demonstrates the importance of
      validation of computational models through the use of experimental in vivo data,
      including the local comparison of simulated and experimental remodeling sites. It
      is assumed that the ability to accurately predict changes in bone micro
      architecture will facilitate a deeper understanding of the cellular mechanisms
      underlying bone remodeling and adaptation due to mechanical loading.

PMID- 21890011
TI  - Prematurity viewed through the social ecological framework.

PMID- 21890012
TI  - Understanding and preventing preterm birth: the power of collaboration.

PMID- 21890013
TI  - Epidemiology: the changing face of preterm birth.
AB  - Preterm birth, defined as a pregnancy ending at less than 37 completed weeks of
      gestation, is the leading cause of infant mortality in the United States. The
      occurrence of preterm births rose steadily from 9.4% of all pregnancies in the
      United States in 1981 to 12.8% in 2006, before declining to 12.7% in 2007 and
      12.3% in 2008. Most of the increase was attributable to increases in multiple
      gestations. Recent research has sought to understand this condition by evaluating
      its familial occurrence and both clinical and pathologic information to derive an
      etiologically homogeneous categorization.

PMID- 21890015
TI  - The role of inflammation and infection in preterm birth.
AB  - Much emphasis in recent decades has been devoted to inflammation and infection as
      a premier causal mechanism of preterm birth. This article explores the
      epidemiologic, clinical, and animal data that exist to support this conceptual
      paradigm as well as proposed mechanisms through which to potentially mitigate the
      adversity of prematurity. Truly successful interventions are not likely to occur
      until the pathogenesis of preterm birth and the role of inflammation in causing
      not only parturition but also fetal and neonatal injury is fully elucidated.

PMID- 21890016
TI  - Abruption-associated prematurity.
AB  - Chronic, subacute decidual hemorrhage (ie, abruptio placenta and retrochorionic
      hematoma formation) is an important contributor to preterm parturition. Such
      hemorrhage induces thrombin from decidual tissue factor, which plays a pivotal
      role in the development of preterm premature rupture of membranes and preterm
      delivery by acting through protease-activated receptors to promote the production
      of pro-inflammatory cytokines, and matrix-degrading metalloproteinases. Severe,
      acute abruption can lead to maternal and fetal mortality. Current management of
      abruption is individualized based on severity of disease, underlying etiology,
      and gestational age.

PMID- 21890017
TI  - Medically indicated--iatrogenic prematurity.
AB  - Premature delivery of an infant is occasionally performed because of
      complications of pregnancy. This article reviews common medical indications for
      preterm delivery and the available evidence supporting delivery before 37 weeks
      of gestation. In many conditions, few data exist to guide optimal timing of
      delivery and management is guided by expert opinion. Ultimately, an individual
      assessment must be made in each case to weigh the risks that pregnancy
      continuation poses to the mother and/or fetus with the risks of prematurity and
      its associated morbidities.

PMID- 21890014
TI  - The contribution of maternal stress to preterm birth: issues and considerations.
AB  - Preterm birth represents the most significant problem in maternal-child health,
      with maternal stress identified as a variable of interest. The effects of
      maternal stress on risk of preterm birth may vary as a function of context. This
      article focuses on select key issues and questions highlighting the need to
      develop a better understanding of which particular subgroups of pregnant women
      may be especially vulnerable to the potentially detrimental effects of maternal
      stress, and under what circumstances and at which stages of gestation. Issues
      related to the characterization and assessment of maternal stress and candidate
      biologic mechanisms are addressed.

PMID- 21890018
TI  - Outcomes of preterm infants: morbidity replaces mortality.
AB  - Over the last 50 years in the United States a rising preterm birth rate, a
      progressive decrease in preterm mortality, and a lowering of the limit of
      viability have made preterm birth a significant public health problem.
      Neuromaturation, the functional development of the central nervous system (CNS),
      is a dynamic process that promotes and shapes CNS structural development. This
      article reviews preterm outcomes, recognizing that multiple factors influence
      neuromaturation and lead to a range of neurodevelopmental disabilities,
      dysfunctions, and altered CNS processing. Ways to protect preterm infants and
      support their growth and development in and beyond intensive care are examined.

PMID- 21890019
TI  - Neuroprotective approaches: before and after delivery.
AB  - Infants born preterm are especially vulnerable to cerebral palsy, the risk of
      which is inversely proportional to gestational age at birth. The contribution of
      prematurity to the overall burden of cerebral palsy is substantial. This article
      reviews and discusses potential antenatal and postnatal neuroprotective
      approaches targeted at the numerous risk factors associated with cerebral palsy
      among preterm infants, including magnesium sulfate.

PMID- 21890020
TI  - Care at the edge of viability: medical and ethical issues.
AB  - Decision-making for extremely immature preterm infants at the margins of
      viability is ethically, professionally, and emotionally complicated. A standard
      for prenatal consultation should be developed incorporating assessment of
      parental decision-making preferences and styles, a communication process
      involving a reciprocal exchange of information, and effective strategies for
      decisional deliberation, guided by and consistent with parental moral framework.
      Professional caregivers providing perinatal consultations or end-of-life
      counseling for extremely preterm infants should be sensitive to these issues and
      be taught flexibility in counseling techniques adhering to consistent guidelines.
      Emphasis must shift away from physician beliefs and behaviors about the
      boundaries of viability.

PMID- 21890021
TI  - Morbidity and mortality in late preterm and early term newborns: a continuum.
AB  - Late preterm and early term infants are at higher risk for short-term and long
      term morbidities and mortality than term infants. Such outcomes are influenced by
      many factors, the strongest of which is gestational age. Counseling and educating
      women and families about risks of late preterm and early term births is helpful
      for timing and route of delivery, managing the pregnancy and infant, and
      prognosticating outcomes for infants.

PMID- 21890022
TI  - What we have here is a failure to communicate: obstacles to optimal care for
      preterm birth.
AB  - Obstetricians and pediatricians share the common goal of a healthy beginning for
      every baby, mother, and family. This article asserts that miscommunication
      between the specialties, fostered by separate definitions, metrics, and outcomes,
      is an impediment to optimal care. Solutions are suggested for improving
      communication and outcomes.

PMID- 21890024
TI  - Late preterm birth: preventable prematurity?
AB  - Prematurity is one of the leading causes of infant morbidity and mortality
      globally. Over the years, however, advances in medicine and technology have
      enhanced the ability to care for babies at very early gestations. There has also
      been a shift in the distribution of births away from term/post-term gestations
      and toward earlier gestational ages. These changes have added to the burden of
      premature births. The focus of this article is to present both sides of the
      story, one that highlights the many problems and morbidities faced by this
      subgroup of premature infants and the other that justifies their early delivery.

PMID- 21890025
TI  - Term pregnancy: time for a redefinition.
AB  - The designation term pregnancy and the distinction between term, preterm, and
      postterm pregnancy carry with them significant clinical implications with respect
      to the management of pregnancy complications. Although the potential hazards of
      both preterm birth and postterm pregnancy have been long recognized, little
      attention has, until recently, been given to the differential morbidity
      experienced by neonates born at different times within the 5-week interval
      classically considered term gestation. This article is a reevaluation of the
      concept of term pregnancy in light of current data.

PMID- 21890023
TI  - Controversy: antenatal steroids.
AB  - There is no controversy that women at risk of preterm delivery before 32 to 34
      weeks' gestational age should be treated with antenatal steroids. Three recent
      meta-analyses by the Cochrane Collaboration on the benefits of antenatal
      steroids, the choice of steroid and dosing, and repeat doses of corticosteroids
      comprehensively summarize the available clinical information to about 2007.
      However, there are many unanswered questions about which steroid and dose to use
      and about their use in selected populations. This review focuses on those areas
      of uncertainty.

PMID- 21890026
TI  - Quality improvement opportunities to prevent preterm births.
AB  - Quality improvement initiatives have been successfully employed in many areas of
      medicine, but few have been implemented in preventing prematurity (or preterm
      birth), which continues to be one of the most common complications in obstetrics,
      and the leading cause of perinatal morbidity and mortality in the United States.
      Due to the complex nature of the causes of prematurity, developing and
      instituting a quality improvement program to prevent prematurity can be
      challenging. However, using proven quality improvement principles and techniques,
      along with institutional will and commitment, are invaluable in rapidly
      implementing evidence-based initiatives for the prevention of preterm births.

PMID- 21890027
TI  - 9/11: ten years on.

PMID- 21890028
TI  - War and peace.

PMID- 21890029
TI  - 9/11--new data, reviews, and reflections.

PMID- 21890030
TI  - Taking the terror out of terrorism: mortality data after 9/11.

PMID- 21890031
TI  - 9/11: the view ahead.

PMID- 21890032
TI  - Medical care for workers exposed to the WTC disaster.

PMID- 21890033
TI  - Suicide attacks--the rationale and consequences.

PMID- 21890034
TI  - Fighting a war, sparing civilians.

PMID- 21890035
TI  - Role of law in global response to non-communicable diseases.

PMID- 21890036
TI  - To err is human.

PMID- 21890038
TI  - Mechthild Prinz: using DNA to identify the victims of 9/11.

PMID- 21890039
TI  - JoAnn Difede: emotional engagement with victims of trauma.

PMID- 21890040
TI  - National, regional, and worldwide estimates of stillbirth rates.

PMID- 21890041
TI  - National, regional, and worldwide estimates of stillbirth rates.

PMID- 21890043
TI  - Stillbirth in high-income countries.

PMID- 21890044
TI  - Stillbirth in high-income countries.

PMID- 21890046
TI  - Stillbirth and healthy timing and spacing of pregnancy.

PMID- 21890048
TI  - Trials of antenatal syphilis screening urgently needed.

PMID- 21890050
TI  - Better understanding needed of physiology of sustaining life in utero.

PMID- 21890051
TI  - Genetic factors in stillbirths.

PMID- 21890052
TI  - Mortality among survivors of the Sept 11, 2001, World Trade Center disaster:
      results from the World Trade Center Health Registry cohort.
AB  - BACKGROUND: The Sept 11, 2001 (9/11) World Trade Center (WTC) disaster has been
      associated with several subacute and chronic health effects, but whether excess
      mortality after 9/11 has occurred is unknown. We tested whether excess mortality
      has occurred in people exposed to the WTC disaster. METHODS: In this
      observational cohort study, deaths occurring in 2003-09 in WTC Health Registry
      participants residing in New York City were identified through linkage to New
      York City vital records and the National Death Index. Eligible participants were
      rescue and recovery workers and volunteers; lower Manhattan area residents,
      workers, school staff and students; and commuters and passers-by on 9/11. Study
      participants were categorised as rescue and recovery workers (including
      volunteers), or non-rescue and non-recovery participants. Standardised mortality
      ratios (SMR) were calculated with New York City rates from 2000-09 as the
      reference. Within the cohort, proportional hazards were used to examine the
      relation between a three-tiered WTC-related exposure level (high, intermediate,
      or low) and total mortality. FINDINGS: We identified 156 deaths in 13,337 rescue
      and recovery workers and 634 deaths in 28,593 non-rescue and non-recovery
      participants. All-cause SMRs were significantly lower than that expected for
      rescue and recovery participants (SMR 0.45, 95% CI 0.38-0.53) and non-rescue and
      non-recovery participants (0.61, 0.56-0.66). No significantly increased SMRs for
      diseases of the respiratory system or heart, or for haematological malignancies
      were found. In non-rescue and non-recovery participants, both intermediate and
      high levels of WTC-related exposure were significantly associated with mortality
      when compared with low exposure (adjusted hazard ratio 1.22, 95% CI 1.01-1.48,
      for intermediate exposure and 1.56, 1.15-2.12, for high exposure). High levels of
      exposure in non-rescue and non-recovery individuals, when compared with low
      exposed non-rescue and non-recovery individuals, were associated with heart
      disease-related mortality (adjusted hazard ratio 2.06, 1.10-3.86). In rescue and
      recovery participants, level of WTC-related exposure was not significantly
      associated with all-cause mortality (adjusted hazard ratio 1.25, 95% CI 0.56
      2.78, for high exposure and 1.03, 0.52-2.06, for intermediate exposure when
      compared with low exposure). INTERPRETATION: This exploratory study of mortality
      in a well defined cohort of 9/11 survivors provides a baseline for continued
      surveillance. Additional follow-up is needed to establish whether these
      associations persist and whether a similar association over time will occur in
      rescue and recovery participants. FUNDING: US Centers for Disease Control and
      Prevention (National Institute for Occupational Safety and Health, Agency for
      Toxic Substances and Disease Registry, and National Center for Environmental
      Health); New York City Department of Health and Mental Hygiene.

PMID- 21890053
TI  - Persistence of multiple illnesses in World Trade Center rescue and recovery
      workers: a cohort study.
AB  - BACKGROUND: More than 50,000 people participated in the rescue and recovery work
      that followed the Sept 11, 2001 (9/11) attacks on the World Trade Center (WTC).
      Multiple health problems in these workers were reported in the early years after
      the disaster. We report incidence and prevalence rates of physical and mental
      health disorders during the 9 years since the attacks, examine their associations
      with occupational exposures, and quantify physical and mental health
      comorbidities. METHODS: In this longitudinal study of a large cohort of WTC
      rescue and recovery workers, we gathered data from 27,449 participants in the WTC
      Screening, Monitoring, and Treatment Program. The study population included
      police officers, firefighters, construction workers, and municipal workers. We
      used the Kaplan-Meier procedure to estimate cumulative and annual incidence of
      physical disorders (asthma, sinusitis, and gastro-oesophageal reflux disease),
      mental health disorders (depression, post-traumatic stress disorder [PTSD], and
      panic disorder), and spirometric abnormalities. Incidence rates were assessed
      also by level of exposure (days worked at the WTC site and exposure to the dust
      cloud). FINDINGS: 9-year cumulative incidence of asthma was 27.6% (number at
      risk: 7027), sinusitis 42.3% (5870), and gastro-oesophageal reflux disease 39.3%
      (5650). In police officers, cumulative incidence of depression was 7.0% (number
      at risk: 3648), PTSD 9.3% (3761), and panic disorder 8.4% (3780). In other rescue
      and recovery workers, cumulative incidence of depression was 27.5% (number at
      risk: 4200), PTSD 31.9% (4342), and panic disorder 21.2% (4953). 9-year
      cumulative incidence for spirometric abnormalities was 41.8% (number at risk:
      5769); three-quarters of these abnormalities were low forced vital capacity.
      Incidence of most disorders was highest in workers with greatest WTC exposure.
      Extensive comorbidity was reported within and between physical and mental health
      disorders. INTERPRETATION: 9 years after the 9/11 WTC attacks, rescue and
      recovery workers continue to have a substantial burden of physical and mental
      health problems. These findings emphasise the need for continued monitoring and
      treatment of the WTC rescue and recovery population. FUNDING: Centers for Disease
      Control and Prevention and National Institute for Occupational Safety and Health.

PMID- 21890054
TI  - Early assessment of cancer outcomes in New York City firefighters after the 9/11
      attacks: an observational cohort study.
AB  - BACKGROUND: The attacks on the World Trade Center (WTC) on Sept 11, 2001 (9/11)
      created the potential for occupational exposure to known and suspected
      carcinogens. We examined cancer incidence and its potential association with
      exposure in the first 7 years after 9/11 in firefighters with health information
      before 9/11 and minimal loss to follow-up. METHODS: We assessed 9853 men who were
      employed as firefighters on Jan 1, 1996. On and after 9/11, person-time for 8927
      firefighters was classified as WTC-exposed; all person-time before 9/11, and
      person-time after 9/11 for 926 non-WTC-exposed firefighters, was classified as
      non-WTC exposed. Cancer cases were confirmed by matches with state tumour
      registries or through appropriate documentation. We estimated the ratio of
      incidence rates in WTC-exposed firefighters to non-exposed firefighters, adjusted
      for age, race and ethnic origin, and secular trends, with the US National Cancer
      Institute Surveillance Epidemiology and End Results (SEER) reference population.
      CIs were estimated with overdispersed Poisson models. Additional analyses
      included corrections for potential surveillance bias and modified cohort
      inclusion criteria. FINDINGS: Compared with the general male population in the
      USA with a similar demographic mix, the standardised incidence ratios (SIRs) of
      the cancer incidence in WTC-exposed firefighters was 1.10 (95% CI 0.98-1.25).
      When compared with non-exposed firefighters, the SIR of cancer incidence in WTC
      exposed firefighters was 1.19 (95% CI 0.96-1.47) corrected for possible
      surveillance bias and 1.32 (1.07-1.62) without correction for surveillance bias.
      Secondary analyses showed similar effect sizes. INTERPRETATION: We reported a
      modest excess of cancer cases in the WTC-exposed cohort. We remain cautious in
      our interpretation of this finding because the time since 9/11 is short for
      cancer outcomes, and the reported excess of cancers is not limited to specific
      organ types. As in any observational study, we cannot rule out the possibility
      that effects in the exposed group might be due to unidentified confounders.
      Continued follow-up will be important and should include cancer screening and
      prevention strategies. FUNDING: National Institute for Occupational Safety and
      Health.

PMID- 21890055
TI  - Casualties in civilians and coalition soldiers from suicide bombings in Iraq,
      2003-10: a descriptive study.
AB  - BACKGROUND: Suicide bombs in Iraq are a major public health problem. We aimed to
      describe documented casualties from suicide bombs in Iraq during 2003-10 in Iraqi
      civilians and coalition soldiers. METHODS: In this descriptive study, we analysed
      and compared suicide bomb casualties in Iraq that were documented in two datasets
      covering March 20, 2003, to Dec 31, 2010--one reporting coalition-soldier deaths
      from suicide bombs, the other reporting deaths and injuries of Iraqi civilians
      from armed violence. We analysed deaths and injuries over time, by bomb subtype
      and victim demographics. FINDINGS: In 2003-10, 1003 documented suicide bomb
      events caused 19% (42,928 of 225,789) of all Iraqi civilian casualties in our
      dataset, 26% (30,644 of 117,165) of injured civilians, and 11% (12,284 of
      108,624) of civilian deaths. The injured-to-killed ratio for civilians was 2.5
      people injured to one person killed from suicide bombs. Suicide bombers on foot
      caused 43% (5314 of 12,284) of documented suicide bomb deaths. Suicide bombers
      who used cars caused 40% (12,224 of 30,644) of civilian injuries. Of 3963
      demographically identifiable suicide bomb fatalities, 2981 (75%) were men, 428
      (11%) were women, and 554 (14%) were children. Children made up a higher
      proportion of demographically identifiable deaths from suicide bombings than from
      general armed violence (9%, 3669 of 40,276 deaths; p<0.0001). The injured-to
      killed ratio for all suicide bombings was slightly higher for women than it was
      for men (p=0.02), but the ratio for children was lower than it was for both women
      (p<0.0001) and men (p=0.0002). 200 coalition soldiers were killed in 79 suicide
      bomb events during 2003-10. More Iraqi civilians per lethal event were killed
      than were coalition soldiers (12 vs 3; p=0.004). INTERPRETATION: Suicide bombers
      in Iraq kill significantly more Iraqi civilians than coalition soldiers. Among
      civilians, children are more likely to die than adults when injured by suicide
      bombs. FUNDING: None.

PMID- 21890056
TI  - Effectiveness of battlefield-ethics training during combat deployment: a
      programme assessment.
AB  - BACKGROUND: Breakdowns in the ethical conduct of soldiers towards non-combatants
      on the battlefield are of grave concern in war. Evidence-based training
      approaches to prevent unethical conduct are scarce. We assessed the effectiveness
      of battlefield-ethics training and factors associated with unethical battlefield
      conduct. METHODS: The training package, based on movie vignettes and leader-led
      discussions, was administered 7 to 8 months into a 15-month high-intensity combat
      deployment in Iraq, between Dec 11, 2007, and Jan 30, 2008. Soldiers from an
      infantry brigade combat team (total population about 3500) were randomly
      selected, on the basis of company and the last four digits of each soldier's
      social security number, and invited to complete an anonymous survey 3 months
      after completion of the training. Reports of unethical behaviour and attitudes in
      this sample were compared with a randomly selected pre-training sample from the
      same brigade. The response patterns for ethical behaviour and reporting of
      ethical violations were analysed with chi-square analyses. We developed two
      logistic regression models using self-reported unethical behaviours as dependent
      variables. Factors associated with unethical conduct, including combat
      experiences and post-traumatic stress disorder (PTSD), were assessed with
      validated scales. FINDINGS: Of 500 randomly selected soldiers 421 agreed to
      participate in the anonymous post-training survey. A total of 397 soldiers of the
      same brigade completed the pre-training survey. Training was associated with
      significantly lower rates of unethical conduct of soldiers and greater
      willingness to report and address misconduct than in those before training. For
      example, reports of unnecessary damage or destruction of private property
      decreased from 13.6% (54 of 397; 95% CI 10.2-17.0) before training to 5.0% (21 of
      421; 2.9-7.1) after training (percent difference -63.2%; p<0.0001), and
      willingness to report a unit member for mistreatment of a non-combatant increased
      from 36.0% (143 of 397; 31.3-40.7) to 58.9% (248 of 421; 54.2-63.6; percent
      difference 63.6; p<0.0001). Nearly all participants (410 [97%]) reported that
      training made it clear how to respond towards non-combatants. Combat frequency
      and intensity was the strongest predictor of unethical behaviour; PTSD was not a
      significant predictor of unethical behaviour after controlling for combat
      experiences. INTERPRETATION: Leader-led battlefield ethics training positively
      influenced soldiers' understanding of how to interact with and treat non
      combatants, and reduced reports of ethical misconduct. Unethical battlefield
      conduct was associated with high-intensity combat but not with PTSD. FUNDING:
      None.

PMID- 21890058
TI  - Islam, medicine, and Arab-Muslim refugee health in America after 9/11.
AB  - Islam is the world's second largest religion, representing nearly a quarter of
      the global population. Here, we assess how Islam as a religious system shapes
      medical practice, and how Muslims view and experience medical care. Islam has
      generally encouraged the use of science and biomedicine for the alleviation of
      suffering, with Islamic authorities having a crucial supportive role. Muslim
      patients are encouraged to seek medical solutions to their health problems. For
      example, Muslim couples who are infertile throughout the world are permitted to
      use assisted reproductive technologies. We focus on the USA, assessing how
      Islamic attitudes toward medicine influence Muslims' engagement with the US
      health-care system. Nowadays, the Arab-Muslim population is one of the fastest
      growing ethnic-minority populations in the USA. However, since Sept 11, 2001,
      Arab-Muslim patients--and particularly the growing Iraqi refugee population--face
      huge challenges in seeking and receiving medical care, including care that is
      judged to be religiously appropriate. We assess some of the barriers to care--ie,
      poverty, language, and discrimination. Arab-Muslim patients' religious concerns
      also suggest the need for cultural competence and sensitivity on the part of
      health-care practitioners. Here, we emphasise how Islamic conventions might
      affect clinical care, and make recommendations to improve health-care access and
      services for Arab-Muslim refugees and immigrants, and Muslim patients in general.

PMID- 21890057
TI  - Short-term and medium-term health effects of 9/11.
AB  - The New York City terrorist attacks on Sept 11, 2001 (9/11), killed nearly 2800
      people and thousands more had subsequent health problems. In this Review of
      health effects in the short and medium terms, strong evidence is provided for
      associations between experiencing or witnessing events related to 9/11 and post
      traumatic stress disorder and respiratory illness, with a correlation between
      prolonged, intense exposure and increased overall illness and disability. Rescue
      and recovery workers, especially those who arrived early at the World Trade
      Center site or worked for longer periods, were more likely to develop respiratory
      illness than were other exposed groups. Risk factors for post-traumatic stress
      disorder included proximity to the site on 9/11, living or working in lower
      Manhattan, rescue or recovery work at the World Trade Center site, event-related
      loss of spouse, and low social support. Investigators note associations between
      9/11 exposures and additional disorders, such as depression and substance use;
      however, for some health problems association with exposures related to 9/11 is
      unclear.

PMID- 21890059
TI  - Adverse health consequences of US Government responses to the 2001 terrorist
      attacks.
AB  - In response to the attacks on Sept 11, 2001 (9/11), and the related security
      concerns, the USA and its coalition partners began a war in Afghanistan and
      subsequently invaded Iraq. The wars caused many deaths of non-combatant
      civilians, further damaged the health-supporting infrastructure and the
      environment (already adversely affected by previous wars), forced many people to
      migrate, led to violations of human rights, and diverted resources away from
      important health needs. After 9/11 and the anthrax outbreak shortly afterwards,
      the USA and other countries have improved emergency preparedness and response
      capabilities, but these actions have often diverted attention and resources from
      more urgent health issues. The documentation and dissemination of information
      about the adverse health effects of these wars and about the diversion of
      resources could help to mitigate these consequences and prevent their recurrence.

PMID- 21890060
TI  - Public health preparedness and response in the USA since 9/11: a national health
      security imperative.

PMID- 21890061
TI  - Redefining of public health preparedness after 9/11.

PMID- 21890062
TI  - Sepsis and spontaneous bacterial peritonitis in Thailand.

PMID- 21890063
TI  - Another good news from TTBDIS.

PMID- 21890064
TI  - Updates on Borrelia burgdorferi sensu lato complex with respect to public health.
AB  - Borrelia burgdorferi sensu lato (s.l.) complex is a diverse group of worldwide
      distributed bacteria that includes 18 named spirochete species and a still not
      named group proposed as genomospecies 2. Descriptions of new species and variants
      continue to be recognized, so the current number of described species is probably
      not final. Most of known spirochete species are considered to have a limited
      distribution. Eleven species from the B. burgdorferi s.l. complex were identified
      in and strictly associated with Eurasia (B. afzelii, B. bavariensis, B. garinii,
      B. japonica, B. lusitaniae, B. sinica, B. spielmanii, B. tanukii, B. turdi, B.
      valaisiana, and B. yangtze), while another 5 (B. americana, B. andersonii, B.
      californiensis, B. carolinensis, and B. kurtenbachii) were previously believed to
      be restricted to the USA only. B. burgdorferi sensu stricto (s.s.), B. bissettii,
      and B. carolinensis share the distinction of being present in both the Old and
      the New World. Out of the 18 genospecies, 3 commonly and 4 occasionally infect
      humans, causing Lyme borreliosis (LB) - a multisystem disease that is often
      referred to as the 'great imitator' due to diversity of its clinical
      manifestations. Among the genospecies that commonly infect people, i.e. B.
      burgdorferi s.s., B. afzelii, and B. garinii, only B. burgdorferi s.s. causes LB
      both in the USA and in Europe, with a wide spectrum of clinical conditions
      ranging from minor cutaneous erythema migrans (EM) to severe arthritis or
      neurological manifestations. The epidemiological data from many European
      countries and the USA show a dramatic increase of the diagnosed cases of LB due
      to the development of new progressive diagnostic methods during the last decades
      (Hubalek, 2009). Recently, the definition of the disease has also changed. What
      was not considered Lyme borreliosis before might be now.

PMID- 21890065
TI  - Prospective study on the incidence of infection by Borrelia burgdorferi sensu
      lato after a tick bite in a highly endemic area of Switzerland.
AB  - The periurban forest of Neuchatel (Switzerland) is a high-risk area for Lyme
      Borreliosis, due to a high density of infected Ixodes ricinus ticks. In this
      study, we evaluated the risk of subclinical (seroconversion) and clinical
      infection after a tick bite in Neuchatel inhabitants from 2003 to 2005.
      Inhabitants have been invited, through media, to visit a physician after a tick
      bite. A questionnaire was filled out and two blood samples were taken at 8-week
      interval. EIA screening tests for IgM and IgG (IMX system, Abbott) were applied
      for paired sera. In case of a change in antibody titres between both samples, a
      homemade Western-blot using Borrelia afzelii, B. burgdorferi sensu stricto and B.
      garinii as antigens was performed. Participants were included into two groups.
      Group one included asymptomatic participants (n=255). Among them, nine (3.5%)
      seroconverted with seroconversion rates varying between 6.8% in 2003, 2.1% in
      2004 and 2.3% in 2005. Participants who developed clinical symptoms of LB were
      included into group two (n=14). Erythema migrans (EM) was reported in 5.2% of
      participants (5.2%), varying between 7.5% in 2003, 5% in 2004 and 3.4% in 2005.
      Ticks obtained from 186 participants were examined for B. burgdorferi infection
      by PCR/Reverse Line Blotting, and by Real Time PCR and tick attachment duration
      was estimated. Among I. ricinus ticks collected from participants, 32.8% were
      infected by B. burgdorferi sensu lato. B. afzelii predominated among these ticks.
      Globally, 65.9% of nymphs remained attached for more than 24h whereas only 38.3%
      of female ticks remained attached for more than 24h. We observed that 6.6% and
      2.4% of participants bitten by infected and uninfected ticks, respectively,
      developed EM.

PMID- 21890066
TI  - Borrelia afzelii ospC genotype diversity in Ixodes ricinus questing ticks and
      ticks from rodents in two Lyme borreliosis endemic areas: contribution of co
      feeding ticks.
AB  - In Europe, the Lyme borreliosis (LB) agents like Borrelia burgdorferi sensu
      stricto (ss), B. afzelii, and B. garinii are maintained in nature by enzoonotic
      transmission cycles between vertebrate hosts and Ixodes ricinus ticks. The outer
      surface protein C is a highly antigenic protein expressed by spirochaetes during
      transmission from ticks to mammals as well as during dissemination in the
      vertebrate hosts. Previous studies based on analysis of ospC gene sequences have
      led to the classification of ospC genotypes into ospC groups. The aim of this
      study was to analyse and compare ospC group distribution among isolates of the
      rodent-associated genospecies, B. afzelii, at 3 levels (questing ticks, ticks
      feeding on rodents, and xenodiagnostic ticks). Isolates were obtained during a
      study carried out in 2 LB endemic areas located on the Swiss Plateau [Portes
      Rouges (PR) and Staatswald (SW)], where rodents were differently infested by co
      feeding ticks (Perez et al., unpublished data). Overall, we identified 10
      different ospC groups with different distributions among isolates from questing
      ticks, ticks that detached from rodents, and xenodiagnostic ticks at the 2 sites.
      We observed a higher ospC diversity among isolates from ticks that fed on rodents
      at SW, and mixed infections with 2 ospC groups were also more frequent among
      isolates from ticks that fed on rodents at SW (n=18) than at PR (n=1). At both
      sites, B. afzelii isolates obtained from larvae that were feeding on the rodents
      simultaneously with nymphs displayed a higher diversity of ospC groups (mean
      number of ospC groups: 2.25 for PR and 1.75 for SW) than isolates from larvae
      feeding without nymphs (mean number of ospC groups: 1.17 for PR and 1 for SW). We
      suggest that co-feeding transmission of Borrelia, previously described in
      laboratory models, contributes in nature in promoting and maintaining ospC
      diversity within local tick populations.

PMID- 21890067
TI  - Genetic diversity in Ixodes scapularis (Acari: Ixodidae) from six established
      populations in Canada.
AB  - Although Ixodes scapularis is the most important vector of Borrelia burgdorferi
      sensu stricto, the causative agent of Lyme disease in North America, little is
      known of the genetic diversity in this tick species within the recently
      established populations in Canada. In the present study, 153 I. scapularis adults
      collected from southern Canada were compared genetically using single-strand
      conformation polymorphism (SSCP) analyses in combination with DNA sequencing of
      the mitochondrial 16S rRNA gene. Nineteen haplotypes were detected, 8 of which
      have not been reported in the U.S.A. One 'new' haplotype was only detected at
      Lunenburg, Nova Scotia, and comprised 38% of the ticks examined for that
      population. The population in the southeast corner of Manitoba contained 3 'new'
      haplotypes. Although the most common haplotype (Is-1) was present in all 6
      populations of I. scapularis in Canada, there were significant differences in the
      genetic structure among population. This suggests different geographical origins
      for the tick populations in Canada, which may be related to the transportation of
      larval and nymphal ticks by migratory passerines using different flyways.
      Determination of the origins of the endemic populations of I. scapularis in
      Canada, as well as those predicted to establish in the near future, has important
      implications with respect to understanding the risk of exposure to pathogenic
      bacteria infecting these ticks.

PMID- 21890068
TI  - Nest box-deployed bait for delivering oral vaccines to white-footed mice.
AB  - Although a wide range of interventions are available for use in reducing the
      public health burden of Lyme disease, additional tools are needed. Vaccinating
      mouse reservoirs may reduce the prevalence of spirochetal infection due to the
      powerful vector and reservoir competence-modulating effects of anti-outer surface
      protein A (OspA) antibody. A delivery system for an oral immunogen would be
      required for field trials of any candidate vaccine. Accordingly, we tested
      candidate bait preparations that were designed to be environmentally stable,
      attractive to mice, and non-nutritive. In addition, we determined whether
      delivery of such baits within nest boxes could effectively target white-footed
      mice. A peanut butter-scented bait was preferred by mice over a blueberry-scented
      one. At a deployment rate of 12.5 nest boxes per hectare, more than half of
      resident mice ingested a rhodamine-containing bait, as demonstrated by
      fluorescent staining of their vibrissae. We conclude that a peanut butter-scented
      hardened bait placed within simple wood nest boxes would effectively deliver
      vaccine to white-footed mice, thereby providing baseline information critical for
      designing field trials of a candidate oral vaccine.

PMID- 21890069
TI  - Human anaplasmosis in Belgium: a 10-year seroepidemiological study.
AB  - Human granulocytic anaplasmosis (HGA) is a tick-borne rickettsial infection of
      neutrophils caused by Anaplasma phagocytophilum. Although the pathogen was known
      as a veterinary agent as early as 1932, the link with human disease was first
      established in 1990. In the past decennium, the involvement of HGA as an
      important and frequent cause of fever with a history of tick bite was
      increasingly recognized in many regions of Europe. This paper presents a 10-year
      A. phagocytophilum serosurveillance (2000-2009), wherein 1672 serum samples were
      tested and 418 were found positive. A total of 111 patients had a history of tick
      bite, fever, and at least a 4-fold rise in titre and are thus considered to be
      confirmed cases. These findings suggest that Belgium is a hot spot for HGA
      infections.

PMID- 21890070
TI  - Toxic effects of various solvents against Rhipicephalus (Boophilus) annulatus.
AB  - The current need of identification of a new acaricidal agent which is acceptable
      to public as environmentally safe is a daring task. Use of herbal acaricides is
      such an alternative. Most of the herbal extracts or fractions are dissolved in
      polar or non-polar solvents or detergents before tested for acaricidal activity.
      The solvent or detergent to be used for dissolving the herbal extract should be
      of little acaricidal activity. In the present study, experimentations were
      carried out on adult engorged female ticks to detect the toxicity of different
      solvents, viz. hexane, petroleum ether, n-butanol, isopropyl alcohol, chloroform,
      glycerol, ethyl acetate, acetone, ethanol, and methanol. The study revealed that
      methanol was the least toxic solvent against Rhipicephalus (Boophilus) annulatus.

PMID- 21890071
TI  - History and critical review of Theileria parva (Boleni), the vaccine stock
      against Zimbabwean cattle theileriosis.
AB  - The paper reviews the infectivity, cross-immunization experiments, and cattle
      vaccination of Zimbabwean cattle-derived Theileria parva (Boleni) sporozoite
      stabilates produced at the Central Veterinary Laboratory (CVL) in Harare between
      1980 and 2003. The Boleni stock was first isolated in July 1978 during a
      theileriosis outbreak and was shown to be virulent in susceptible cattle.
      Thereafter, the reactions observed in susceptible cattle produced by different
      tick stabilates derived from the original have been mostly severe (76%) or
      moderate (24%). The parasite concentrations in the Boleni vaccine, the vaccines
      used in East Africa, and a Malawian stock were compared. The infective Theileria
      sporozoite concentration in 1 ml of stabilate in the Muguga and Serengeti (from
      East Africa) and Kasoba (from Malawi) vaccines were 8*, 9*, and 14* the
      concentration of the Boleni stabilate, respectively. The Boleni strain, like the
      other Zimbabwean T. parva isolates, produces a characteristic low piroplasm
      parasitaemia of usually less than 1% in susceptible cattle. This has largely
      contributed to the difference in infection rates (1963; average 40%) among tick
      batches used to prepare the various stabilates. Subsequently, the sporozoite
      concentrations in 1 ml of stabilate also varied considerably (6-91; average 53),
      making the reproducibility and standardization of the stabilates for immunization
      difficult. Immunization of cattle using Boleni stabilates with oxytetracycline
      therapy or with titrated low doses without treatment was found to be safe and
      efficacious. Cross-immunity experiments demonstrated that T. parva Boleni
      stabilates cross-protected against all the Zimbabwean cattle-derived T. parva
      stocks tested. The characteristics of the Boleni stock in affording a wide
      spectrum of cross-protection make it an excellent candidate for cattle
      immunization in Zimbabwe, hence protecting the country from the introduction of
      foreign vaccines and subsequently, foreign parasite populations.

PMID- 21890072
TI  - Clinical and haematological study on water buffaloes (Bubalus bubalis) and
      crossbred cattle naturally infected with Theileria annulata in Sharkia province,
      Egypt.
AB  - This study was conducted to investigate the clinical and haematological findings
      in water buffaloes and crossbred cattle naturally infected with Theileria
      annulata with special reference to the clinical picture of tropical theileriosis
      in Egyptian buffaloes. A total 50 field cases of buffaloes and cattle was
      clinically and laboratory investigated from March to June 2008. Forty-four
      buffaloes and cattle out of 50 were naturally infected with T. annulata and
      showed typical signs of infection. Six animals showed no clinical signs and were
      free from external, internal, and blood parasites. The clinical findings of
      examined cattle and buffaloes showed typical signs of tropical theileriosis:
      fever, enlargement of the superficial lymph nodes, severe lacrimation, bilateral
      conjunctivitis, photophobia, and corneal opacity. It was clear that the severity
      of clinical signs in infected buffaloes was more prominent than in infected
      cattle with persistence of some lesions after recovery as corneal opacity and
      pulmonary lesions. Haematological analysis revealed a significant decrease in
      RBCS count, PCV%, haemoglobin amount, and WBCs in the infected animals when
      compared to the control group. It was concluded from our study that T. annulata
      infection is associated with impairment and alteration of blood parameters in
      both cattle and water buffaloes. Theileriosis in water buffaloes might cause
      irreversible ocular changes that could lead to complete blindness. Data obtained
      in this study might be the basis for subsequent studies under natural and
      experimental field conditions.

PMID- 21890073
TI  - Relationships between tick counts and coat characteristics in Nguni and Bonsmara
      cattle reared on semiarid rangelands in South Africa.
AB  - Indigenous Nguni cattle are adapted to the semiarid rangeland and appear to be
      resistant to ticks; however, the mechanism for tick resistance is yet to be
      established. To understand tick resistance in cattle, relationships among skin
      thickness, hair length, coat score, and tick counts were estimated in Nguni
      (n=12) and Bonsmara (n=12) heifers on semiarid rangelands of South Africa. The
      tick species observed to infest the heifers were Rhipicephalus (Boophilus)
      decoloratus (frequency: 76%), Rhipicephalus (Boophilus) microplus (9%), Amblyomma
      hebraeum (5%), Rhipicephalus appendiculatus (5%), Rhipicephalus evertsi evertsi
      (3%), and Hyalomma marginatum (2%). Nguni heifers had lower (P<0.05) log(10)
      (x+1)-transformed coat scores (0.6+/-0.01), hair length (1.4+/-0.01), and tick
      counts (1.4+/-0.03) than Bonsmara heifers whose log(10) (x+1)-transformed coat
      score, hair length, and tick count values were 0.7+/-0.01, 1.5+/-0.01, and 1.8+/
      0.02, respectively. The skin thickness between the two breeds were similar
      (P>0.05). There was a positive linear (P<0.05) relationship between log(10) (x+1)
      tick counts and log(10) (x+1) coat score in the Nguni (y=1.90x-0.40) and a
      quadratic relationship in the Bonsmara (y=-7.98x(2)+12.74x-3.12) breed. It was
      concluded that the smooth coats may be one of the important mechanisms of tick
      resistance in the indigenous Nguni breed. Determination of genetic resistance to
      ticks in the Nguni breed is recommended as this will give more specific
      indication to the mechanism of host resistance in this breed.

PMID- 21890074
TI  - [Diagnostic and treatment of leg ulcers].
AB  - Ulcers are a frequent cause of dermatologic consultation, and most correspond to
      leg ulcers. Major advances in the treatment of ulcers have occurred in recent
      years as a result of research that has led to new concepts such as the
      consideration of the chronic ulcer as an inflammatory process involving
      proinflammatory cytokines and deficits of growth factors. Furthermore, studies
      into the use of the wet dressing have led to the appearance of a wide variety of
      new dressings. The aim of this review is to update the reader's knowledge of the
      treatment of ulcers in general and of leg ulcers in particular, with a detailed
      description of the new dressings available and of the new therapies for use in
      refractory cases.

PMID- 21890075
TI  - Wearable defibrillator in congenital structural heart disease and inherited
      arrhythmias.
AB  - Patients with congenital structural heart disease (CSHD) and inherited
      arrhythmias (IAs) are at high risk of ventricular tachyarrhythmias and sudden
      cardiac death. The present study was designed to evaluate the short- and long
      term outcomes of patients with CSHD and IA who received a wearable cardioverter
      defibrillator (WCD) for the prevention of sudden cardiac death. The study
      population included 162 patients with CSHD (n = 43) and IA (n = 119) who were
      prospectively followed up in a nationwide registry from 2005 to 2010. The
      mortality rates were compared using Kaplan-Meier survival analysis. The mean age
      of the study patients was 38 +/- 27 years. The patients with CSHD had a greater
      frequency of left ventricular dysfunction (ejection fraction <30%) than did the
      patients with IA (37% vs 5%, respectively; p = 0.002). The predominant indication
      for WCD was pending genetic testing in the IA group and transplant listing in the
      CSHD group. Compliance with the WCD was similar in the 2 groups (91%). WCD shocks
      successfully terminated 3 ventricular tachyarrhythmias in the patients with IA
      during a median follow-up of 29 days of therapy (corresponding to 23 appropriate
      WCD shocks per 100 patient-years). No arrhythmias occurred in the patients with
      CSHD during a median follow-up of 27 days. No patients died while actively
      wearing the WCD. At 1 year of follow-up, the survival rates were significantly
      lower among the patients with CSHD (87%) than among the patients with IA (97%, p
      = 0.02). In conclusion, our data suggest that the WCD can be safely used in high
      risk adult patients with IA and CSHD. Patients with IA showed a greater rate of
      ventricular tachyarrhythmias during therapy but significantly lower long-term
      mortality rates.

PMID- 21890076
TI  - Clinical and echocardiographic predictors of outcomes in patients with apical
      hypertrophic cardiomyopathy.
AB  - Apical hypertrophic cardiomyopathy (HC) is considered to have a favorable
      prognosis, but recent observations have suggested less benign clinical courses.
      We investigated the outcomes in patients with apical HC and evaluated the
      predictors. All 454 patients with apical HC (316 men, age 61 +/- 11 years) were
      recruited. Major cardiovascular events (MACE) were defined as unplanned
      hospitalization because of heart failure, stroke, or cardiovascular mortality.
      The patients were divided into 2 groups: group 1 with MACE and group 2 without
      MACE. During the follow-up period (43 +/- 20 months), the all-cause mortality
      rate was 9% (39 of 454), and 110 patients (25%) had MACE. The subjects in group 1
      were older and a greater proportion had diabetes, hypertension, and atrial
      fibrillation. On the echocardiogram, the left atrial volume index (left atrial
      volume index 36 +/- 17 vs 31 +/- 12 ml/m(2)), transmitral E velocity (65 +/- 17
      vs 61 +/- 16 cm/s), mitral annulus Ea velocity (4.5 +/- 1.4 vs 5.1 +/- 1.8 cm/s),
      Sa velocity (5.8 +/- 1.4 vs 6.6 +/- 1.4 cm/s), E/Ea ratio (15 +/- 5 vs 13 +/- 5),
      and right ventricular systolic pressure (31 +/- 8 vs 28 +/- 7 mm Hg) were
      significantly different between groups 1 and 2 (p <0.05 for all). The left atrial
      volume index (for each 1-ml/m(2) increase, hazard ratio 1.01, 95% confidence
      interval 1.00 to 1.03; p = 0.047), Sa velocity (hazard ratio 0.83, 95% confidence
      interval 0.72 to 0.96, p = 0.014), and E/Ea ratio (hazard ratio 1.04, 95%
      confidence interval 1.00 to 1.09, p = 0.030) were independent predictors of a
      poor prognosis, along with age and the presence of diabetes or hypertension. In
      conclusion, the clinical outcomes of patients with apical HC were less benign in
      older patients and in those with hypertension or diabetes. In addition, the left
      atrial volume index, Sa velocity, and E/Ea ratio were predicters of a poor
      prognosis in patients with apical HC.

PMID- 21890078
TI  - Maternal and paternal environmental risk factors, metabolizing GSTM1 and GSTT1
      polymorphisms, and congenital heart disease.
AB  - Congenital heart defects (CHDs) are the most prevalent of all birth malformations
      arising from the complex interplay of environmental exposures and genes.
      Modifiable environmental risk factors are still largely unknown, especially for
      paternal exposure. The aim of the present study was to examine the association
      between the environmental exposures of both parents and CHD risk and to explore
      the modification effect of metabolizing gene polymorphisms in children who lack
      the genetic capacity to produce the glutathione S-transferase (GST) GSTM1 and
      GSTT1 enzymes. A total of 330 parents of a child with CHD and 330 parents of a
      child without any congenital malformations were compared in terms of lifestyle
      habits and toxicant exposure. GST gene polymorphisms were investigated in 180
      patients with CHD (104 males, age 4.9 +/- 5.8 years). Paternal smoking (>=15
      cigarettes/day) was significantly associated with CHD risk (odds ratio [OR] 2.1,
      95% confidence interval [CI] 1.3 to 3.5, p = 0.002). Both maternal (OR 2.6, 95%
      CI 1.6 to 4.2, p <0.0001) and paternal (OR 2.5, 95% CI 1.6 to 3.8, p <0.0001)
      occupational/environmental exposures increased the risk of CHD. Also, a
      significant additive risk (OR 4.5, 95% CI 2.5 to 8.3, p <0.0001) was found when
      both parents were exposed to toxicants. Both maternal (OR 3.6, 95% CI 1.1 to
      11.2, p = 0.03) and paternal (OR 3.3, 95% CI 1.0 to 10.8, p = 0.03) exposure to
      toxicants increased the CHD risk in children who carried the combined null GST
      genotypes. The effect for the combined null GST genotypes was also stronger (OR
      6.5, 95% CI 1.5 to 28.0) when both parents were exposed. In conclusion, paternal
      smoking and exposure to toxicants for both parents affect the risk of children
      with CHD. Polymorphisms in GST genes can modify a person's risk of toxicant
      exposure-induced disease.

PMID- 21890077
TI  - Comparison of bare-metal and drug-eluting stents in patients with chronic kidney
      disease (from the NHLBI Dynamic Registry).
AB  - Patients with chronic kidney disease (CKD) have a disproportionate burden of
      coronary artery disease and commonly undergo revascularization. The role and
      safety of percutaneous coronary intervention (PCI) using drug-eluting stents
      (DESs) verses bare-metal stents in patients with CKD not on renal replacement
      therapy has not been fully evaluated. This study investigated the efficacy and
      safety of DES in patients with CKD not on renal replacement therapy. Patients
      were drawn from the National Heart, Lung, and Blood Institute Dynamic Registry
      and were stratified by renal function based on estimated glomerular filtration
      rate (GFR). Of the 4,157 participants, 1,108 had CKD ("low GFR" <60 ml/min/1.73
      m(2)), whereas 3,049 patients had normal renal function ("normal GFR" >=60
      ml/min/1.73 m(2)). For each stratum of renal function we compared risk of death,
      myocardial infarction, or repeat revascularization between subjects who received
      DESs and bare-metal stents at the index procedure. Patients with low GFR had
      higher 1-year rates of death and myocardial infarction and a decreased rate of
      repeat revascularization compared to patients with normal GFR. Use of DESs was
      associated with a decreased need for repeat revascularization in the normal-GFR
      group (adjusted hazard ratio 0.63, 95% confidence interval 0.50 to 0.79, p
      <0.001) but not in the low-GFR group (hazard ratio 0.69, 95% confidence interval
      0.45 to 1.06, p = 0.09). Risks of death and myocardial infarction were not
      different between the 2 stents in either patient population. In conclusion,
      presence of CKD predicted poor outcomes after PCI with high rates of mortality
      regardless of stent type. The effect of DES in decreasing repeat
      revascularization appeared to be attenuated in these patients.

PMID- 21890079
TI  - Relation of milrinone after surgery for congenital heart disease to significant
      postoperative tachyarrhythmias.
AB  - Milrinone reduces the risk of low cardiac output syndrome for some pediatric
      patients after congenital heart surgery. Data from adults undergoing cardiac
      surgery suggest an association between milrinone and an increased risk of
      postoperative arrhythmias. We tested the hypothesis that milrinone is an
      independent risk factor for tachyarrhythmias after congenital heart surgery.
      Subjects undergoing congenital heart surgery at our institution were
      consecutively enrolled for 38 months, through September 2010. The data were
      prospectively collected, including a review of full-disclosure telemetry and the
      medical records. Within 38 months, 603 enrolled subjects underwent 724 operative
      procedures. The median age was 5.5 months (range 0.0 to 426), the median weight
      was 6.0 kg (range 0.7 to 108), and the cohort was 45% female. The overall
      arrhythmia incidence was 50%, most commonly monomorphic ventricular tachycardia
      (n = 85, 12%), junctional ectopic tachycardia (n = 69, 10%), accelerated
      junctional rhythm (n = 58, 8%), and atrial tachyarrhythmias (including atrial
      fibrillation, atrial flutter, and ectopic or chaotic atrial tachycardia, n = 58,
      8%). Multivariate logistic regression analysis demonstrated that independent of
      age <1 month, the use of cardiopulmonary bypass, the duration of cardiopulmonary
      bypass, Risk Adjusted classification for Congenital Heart Surgery, version 1,
      score >3, and the use of epinephrine or dopamine, milrinone use on admission to
      the cardiac intensive care unit remained independently associated with an
      increase in the odds of postoperative tachyarrhythmia resulting in an
      intervention (odds ratio 2.8, 95% confidence interval 1.3 to 6.0, p = 0.007). In
      conclusion, milrinone use is an independent risk factor for clinically
      significant tachyarrhythmias in the early postoperative period after congenital
      heart surgery.

PMID- 21890080
TI  - Comparison of the frequency of coronary artery disease in alcohol-related versus
      non-alcohol-related endstage liver disease.
AB  - There are conflicting data as to the prevalence of coronary artery disease (CAD)
      in patients with end-stage liver disease (ESLD) being assessed for liver
      transplantation (LT). The aims of this study were to compare the prevalence of
      CAD in patients with alcohol-related versus non-alcohol-related ESLD and to
      assess the diagnostic utility of dobutamine stress echocardiography (DSE) in
      predicting angiographically important CAD. Consecutive patients with ESLD being
      assessed for LT (n = 420, mean age 56 +/- 8 years) were identified and divided
      into groups of those with alcohol-related ESLD (n = 125) and non-alcohol-related
      ESLD (n = 295). Demographic characteristics, CAD risk factors, results of DSE,
      and coronary angiographic characteristics were recorded. There were no
      significant differences in age or CAD risk factors between groups. The incidence
      of severe CAD (>70% diameter stenosis) was 2% in the alcohol-related ESLD group
      and 13% in the non-alcohol-related ESLD group (p <0.005). In the 2 groups, the
      presence of >=1 CAD risk factor was associated with significant CAD (p <0.05 for
      all). Absence of cardiac risk factors was highly predictive in ruling out
      angiographically significant disease (negative predictive value 100% for alcohol
      related ESLD and 97% for non-alcohol-related ESLD). DSE was performed in 205
      patients. In the 2 groups, DSE had poor predictive value for diagnosing
      significant CAD but was useful in ruling out patients without significant disease
      (negative predictive value 89% for alcohol-related ESLD and 80% for non-alcohol
      related ESLD). In conclusion, there was a significantly lower prevalence of
      severe CAD in patients with alcohol-related ESLD. These findings suggest that
      invasive coronary angiography may not be necessary in this subgroup, particularly
      in the absence of CAD risk factors and negative results on DSE.

PMID- 21890081
TI  - Effects of high adherence to mediterranean or low-fat diets in medicated
      secondary prevention patients.
AB  - Although the Mediterranean diet (MD) and the low-fat Therapeutic Lifestyle
      Changes Diet (TLCD) promote equivalent increases in event-free survival in
      secondary coronary prevention, possible mechanisms of such complete dietary
      patterns in these patients, usually medicated, are unclear. The aim of this study
      was to investigate the effects of the MD versus the TLCD in markers of
      endothelial function, oxidative stress, and inflammation after acute coronary
      syndromes. Comparison was made between 3 months of the MD (n = 21; rich in whole
      grains, vegetables, fruits, nuts, and olive oil, plus red wine) and the TLCD (n =
      19; plus phytosterols 2 g/day) in a highly homogenous population of stable
      patients who experienced coronary events in the previous 2 years (aged 45 to 65
      years, all men) allocated to each diet under a strategy designed to optimize
      adherence, documented as >90%. Baseline demographics, body mass index and
      clinical data, and use of statins and other drugs were similar between groups.
      The MD and TLCD promoted similar decreases in body mass index and blood pressure
      (p <=0.001) and particularly in plasma asymmetric dimethylarginine levels (p =
      0.02) and l-arginine/asymmetric dimethylarginine ratios (p = 0.01). The 2 diets
      did not further enhance flow-mediated brachial artery dilation compared to
      baseline (4.4 +/- 4.0%). Compared to the TLCD, the MD promoted decreases in blood
      leukocyte count (p = 0.025) and increases in high-density lipoprotein levels (p =
      0.053) and baseline brachial artery diameter. Compared to the MD, the TLCD
      decreased low-density lipoprotein and oxidized low-density lipoprotein plasma
      levels, although the ratio of oxidized to total low-density lipoprotein remained
      unaltered. Glucose, high-sensitivity C-reactive protein, triglycerides,
      myeloperoxidase, intercellular adhesion molecular, vascular cell adhesion
      molecule, and glutathione serum and plasma levels remained unchanged with either
      diet. In conclusion, medicated secondary prevention patients show evident
      although small responses to the MD and the TLCD, with improved markers of redox
      homeostasis and metabolic effects potentially related to atheroprotection.

PMID- 21890082
TI  - Effects of QRS duration and pacing location on pressure-volume loop evaluation of
      cardiac resynchronization therapy in end-stage heart failure.
AB  - Cardiac resynchronization therapy (CRT) decreases the morbidity and mortality in
      patients with end-stage heart failure. However, patient selection remains
      challenging, because a considerable 30% to 50% do not respond. Controversy exists
      on the cutoff values for the QRS duration and the optimal lead location. The
      present study relates these parameters on an individual basis to acute pump
      function improvement using invasively obtained pressure-volume loops. Fifty-seven
      patients with symptomatic end-stage heart failure were included in our temporary
      biventricular stimulation study and were grouped according to the QRS duration
      (QRS <20 ms, QRS >=120 ms but <150 ms, and QRS >=150 ms). All patients underwent
      pressure-volume loop assessment of the response to biventricular pacing,
      comparing the baseline measurements to both right ventricular apex pacing
      combined with a left ventricular lead in the posterolateral and anterolateral
      region of the LV. Group analysis during conventional (posterolateral and right
      ventricular apex) CRT did not show improvement in stroke work and dP/dt(max) (
      2%, p = NS; and -7%; p <0.001) in the narrow QRS group but a significant increase
      in the intermediate (+27%, p = 0.020, and +5%, p = 0.044) and wide (+48%, p =
      0.002, and +18%, p <0.001) QRS groups. CRT using the anterolateral and right
      ventricular apex configuration evoked a consistently lower response compared to
      posterolateral and right ventricular apex, resulting in a significant hemodynamic
      deterioration in the narrow QRS group. However, analysis on an individual basis
      identified 25% of patients with narrow QRS duration showing possible hemodynamic
      benefit from CRT compared to 83% of patients with intermediate and wide QRS
      combined. In contrast, 15% of patients had deterioration by conventional
      (posterolateral right ventricular apex) CRT in the intermediate and wide QRS
      groups compared to 31% in the narrow QRS group; 19% of patients could be improved
      by lead placement in the anterolateral rather than the posterolateral region. In
      conclusion, the acute hemodynamic response to CRT is generally in line with the
      long-term results from large randomized trials; however, the individual variation
      is large. The temporary biventricular stimulation protocol might aid in
      individual patient selection and in research aiming at a reduction of
      nonresponders and improvement in lead positioning.

PMID- 21890083
TI  - Long-term safety and efficacy of Pitavastatin in patients with acute myocardial
      infarction (from the Livalo Acute Myocardial Infarction Study [LAMIS]).
AB  - Pitavastatin is a potent lipophilic statin and may play an important role in
      acute myocardial infarction (AMI) but there have been limited data on the safety
      and efficacy of pitavastatin in AMI. This study consisted of 1,039 consecutive
      patients with AMI (74.0% men, mean age 61.4 +/- 12.6 years) who presented in 10
      major percutaneous coronary intervention centers in Korea from February 2007
      through September 2009. Pitavastatin 2 mg/day was routinely administered in
      patients with AMI from time of presentation. We investigated changes of lipid
      profiles, biochemical markers, adverse events, and clinical outcomes up to 12
      months. During the study 318 events overall occurred in 220 patients (21.2%) who
      reported >=1 treatment emergent adverse event, although 20 events in 14 patients
      (1.4%) were treatment-related adverse events. Low-density lipoprotein (LDL)
      cholesterol percent change was -25.6% and LDL cholesterol target attainment was
      70.5% at 12-month follow-up. Levels of creatinine phosphokinase, serum glutamic
      oxaloacetic transaminase, glutamic pyruvic transaminase, and high-sensitivity C
      reactive protein decreased significantly during the first 1 month of pitavastatin
      treatment and were sustained to 12-month follow-up. Major adverse cardiac events
      occurred in 66 patients (7.3%). All-cause deaths occurred in 32 patients (3.5%)
      including 19 (2.1%) cardiac deaths and recurrent MIs occurred in 14 (1.6%) and
      target lesion revascularizations in 42 (4.7%). In conclusion, administration of
      pitavastatin 2 mg/day in patients with AMI showed 70.5% LDL cholesterol target
      attainment with good tolerance and was associated with favorable clinical
      outcomes up to 12 months.

PMID- 21890084
TI  - Acute safety and 30-day outcome after percutaneous edge-to-edge repair of mitral
      regurgitation in very high-risk patients.
AB  - Percutaneous edge-to-edge mitral valve repair using the MitraClip device has
      evolved as a new tool for the treatment of severe mitral valve regurgitation.
      This technique has been evaluated in surgical low- and high-risk patients.
      Patients with advanced age, multiple morbidities, and heart failure will be the
      first to be considered for a nonsurgical approach. Thus safety and feasibility
      data in very high-risk patients are crucial for clinical decision making. The aim
      of this study was to assess short-term safety and clinical efficacy in high-risk
      patients with a Society of Thoracic Surgeons (STS) score >15% after MitraClip
      implantation (mean STS score 24 +/- 4%). All relevant complications, mortality,
      echocardiographic improvement, and changes in brain natriuretic peptide, high
      sensitive troponin T, 6-minute walk distance test, and New York Heart Association
      functional class were collected in patients within 30 days after MitraClip
      implantation. Mitral regurgitation had significantly decreased after 30 days from
      grade 2.9 +/- 0.2 to 1.7 +/- 0.7 (p < 0.0001). Accordingly, New York Heart
      Association functional class had significantly improved from 3.38 +/- 0.59 to 2.2
      +/- 0.4 (p <0.001). Objective parameters of clinical improvement showed a
      significant increase in 6-minute walk distance test (from 194 +/- 44 to 300 +/-
      70 m, p <0.01) and insignificant trends in brain natriuretic peptide (10,376 +/-
      1,996 vs 4,385 +/- 1,266 ng/L, p = 0.06) and high-sensitive troponin T (43 +/-
      8.9 vs 36 +/- 7.7 pg/L, p = 0.27) improvement. Thirty-day mortality was 0. Two
      patients developed a left atrial thrombus, 1 patient was on a ventilator for >12
      hours, and 1 patient had significant access site bleeding. In conclusion, this
      study shows that percutaneous edge-to-edge mitral valve repair can be safely
      performed even in surgical high-risk patients with an STS score >15. At 1-month
      follow-up most patients showed persistent improvement in mitral regurgitation and
      a clinical benefit.

PMID- 21890085
TI  - Pulmonary function in patients with acute coronary syndrome treated with
      ticagrelor or clopidogrel (from the Platelet Inhibition and Patient Outcomes
      [PLATO] pulmonary function substudy).
AB  - The Platelet Inhibition and Patient Outcomes (PLATO) trial showed that ticagrelor
      reduced the risk for cardiovascular events in patients with acute coronary
      syndromes compared to clopidogrel but was associated with increased incidence of
      dyspnea. This substudy assessed whether ticagrelor affects pulmonary function in
      patients with acute coronary syndromes: 199 patients enrolled in the PLATO trial
      and receiving randomized treatment with ticagrelor 90 mg twice daily (n = 101) or
      clopidogrel 75 mg/day (n = 98) took part in the pulmonary function substudy.
      Patients with advanced lung disease, congestive heart failure, or coronary artery
      bypass graft surgery after the index event were excluded. Pulse oximetry (blood
      oxygen saturation), spirometry (forced expiratory volume in 1 second, forced
      vital capacity, and forced expiratory flow between 25% and 75% of forced vital
      capacity before and 20 minutes after inhalation of a beta(2) agonist), lung
      volumes (total lung capacity, functional residual capacity, residual volume), and
      diffusion capacity were performed after patients received study medication for 30
      to 40 days. Tests were then repeated <10 days before and approximately 30 days
      after the discontinuation of study medication. After a mean treatment duration of
      31 days, there were no differences between the groups for any of the pulmonary
      function parameters. At the end of treatment (mean 211 days) and after the
      discontinuation of study medication (mean 32 days after the last dose), there was
      also no evidence of a change in pulmonary function in either group. For example,
      forced expiratory volume in 1 second values before beta(2) agonist inhalation in
      the ticagrelor and clopidogrel groups were 2.81 +/- 0.73 and 2.70 +/- 0.84 L,
      respectively, at the first visit and did not change significantly at subsequent
      visits. In conclusion, no effect of ticagrelor on pulmonary function was seen in
      this cohort of patients with acute coronary syndromes compared to clopidogrel.

PMID- 21890086
TI  - Predictors of response to cardiac resynchronization therapy in patients with a
      non-left bundle branch block morphology.
AB  - Patients with non-left bundle branch block (LBBB) morphologies are thought to
      derive less benefit from cardiac resynchronization therapy (CRT) than those with
      LBBB. However, some patients do exhibit improvement. The characteristics
      associated with a response to CRT in patients with non-LBBB morphologies are
      unknown. Clinical, electrocardiographic, and echocardiographic data were
      collected from 850 consecutive patients presenting for a new CRT device. For
      inclusion, all patients had a left ventricular ejection fraction of <=35%, a QRS
      duration of >=120 ms, and baseline and follow-up echocardiograms available.
      Patients with a paced rhythm or LBBB were excluded. The response was defined as
      an absolute decrease in left ventricular end-systolic volume of >=10% from
      baseline. Multivariate models were constructed to identify variables
      significantly associated with the response and long-term outcomes. A total of 99
      patients met the inclusion criteria. Of these 99 patients, 22 had right bundle
      branch block and 77 had nonspecific intraventricular conduction delay; 52.5% met
      the criteria for response. On multivariate analysis, the QRS duration was the
      only variable significantly associated with the response (odds ratio per 10-ms
      increase 1.23, 95% confidence interval 1.01 to 1.52, p = 0.048). During a mean
      follow-up of 5.4 +/- 0.9 years, 65 patients died or underwent heart transplant or
      left ventricular assist device placement. On multivariate analysis, the QRS
      duration was inversely associated with poor long-term outcomes (hazard ratio per
      10-ms increase 0.79, 95% confidence interval 0.66 to 0.94, p = 0.005). In
      patients with advanced heart failure and non-LBBB morphologies, a wider baseline
      QRS duration is an important determinant of enhanced reverse ventricular
      remodeling and improved long-term outcomes after CRT.

PMID- 21890087
TI  - Comparison of outcomes of patients >= 80 years of age having percutaneous
      coronary intervention according to presentation (stable vs unstable angina
      pectoris/non-ST-segment elevation myocardial infarction vs ST-segment elevation
      myocardial infarction).
AB  - Patients >= 80 years old with coronary artery disease constitute a particular
      risk group in relation to percutaneous coronary intervention (PCI). From 2002
      through 2008 we examined the annual proportion of patients >= 80 years old
      undergoing PCI in western Denmark, their indications for PCI, and prognosis. From
      2002 through 2009 all elderly patients treated with PCI were identified in a
      population of 3.0 million based on the Western Denmark Heart Registry. Cox
      regression analysis was used to compare mortality rates according to clinical
      indications controlling for potential confounding. In total 3,792 elderly
      patients (>= 80 years old) were treated with PCI and the annual proportion
      increased from 224 (5.4%) in 2002 to 588 (10.2%) in 2009. The clinical indication
      was stable angina pectoris (SAP) in 30.2%, ST-segment elevation myocardial
      infarction (STEMI) in 35.0%, UAP/non-STEMI in 29.7%, and "ventricular arrhythmia
      or congestive heart failure" in 5.1%. Overall 30-day and 1-year mortality rates
      were 9.2% and 18.1%, respectively. Compared to patients with SAP the adjusted 1
      year mortality risk was significantly higher for patients presenting with STEMI
      (hazard ratio 3.86, 95% confidence interval 3.08 to 4.85), UAP/non-STEMI (hazard
      ratio 1.95, 95% confidence interval 1.53 to 2.50), and ventricular arrhythmia or
      congestive heart failure (hazard ratio 2.75, 95% confidence interval 1.92 to
      3.92). In patients with SAP target vessel revascularization decreased from 7.1%
      in 2002 to 2.5% in 2008. In conclusion, the proportion of patients >= 80 years
      old treated with PCI increased significantly over an 8-year period. Patients with
      SAP had the lowest mortality rates and rates of clinically driven target vessel
      revascularization decreased over time.

PMID- 21890088
TI  - Relation of C-reactive protein to endothelial fibrinolytic function in healthy
      adults.
AB  - Increased plasma concentrations of C-reactive protein (CRP) independently predict
      future atherothrombotic events in healthy asymptomatic adults. CRP may promote
      atherothrombosis by altering fibrinolytic balance; however, the influence of
      increased plasma CRP concentrations on endothelial fibrinolysis in healthy adults
      is unclear. We tested the hypothesis that endothelial release of tissue-type
      plasminogen activator (t-PA) is impaired in adults with increased plasma CRP
      concentrations independent of other cardiometabolic risk factors. Fifty-four
      healthy adults were studied: 24 with CRP <1.0 mg/L (low CRP; 18 men and 6 women,
      55 +/- 2 years old), 18 with CRP 1.0 to 3.0 mg/L (moderate CRP; 8 men and 10
      women, 58 +/- 2 years old), and 12 with CRP >3.0 mg/L (high CRP; 7 men and 5
      women, 56 +/- 2 years old). Net endothelial release of t-PA was determined in
      vivo in response to intrabrachial infusions of bradykinin (125 to 500 ng/min) and
      sodium nitroprusside (2.0 to 8.0 MUg/min). Capacity of the endothelium to release
      t-PA was significantly lower (~30%) in the high (0.32 +/- 0.5 to 38.9 +/- 6.0 ng
      . 100 ml tissue(-1) . min(-1)) and moderate (-0.05 +/- 0.4 to 39.3 +/- 5.2 ng .
      100 ml tissue(-1) . min(-1)) compared to the low (0.42 +/- 0.9 to 61.8 +/- 5.2 ng
      . 100 ml tissue(-1) . min(-1)) CRP group. There was no significant difference in
      t-PA release between the high and moderate CRP groups. Plasma CRP concentrations
      were inversely related to t-PA release (r = -0.38, p <0.05). In conclusion, these
      results indicate that the capacity of the endothelium to release t-PA is
      decreased in adults with plasma CRP >=1.0 mg/L. Endothelial fibrinolytic
      dysfunction may underlie the increased atherothrombotic risk associated with
      increases in plasma CRP concentrations in otherwise healthy adults.

PMID- 21890089
TI  - Usefulness of serial N-terminal pro-B-type natriuretic peptide measurements for
      determining prognosis in patients with pulmonary arterial hypertension.
AB  - Previous studies have shown the prognostic benefit of N-terminal pro-brain
      natriuretic peptide (NT-pro-BNP) in pulmonary arterial hypertension (PAH) at time
      of diagnosis. However, there are only limited data on the clinical utility of
      serial measurements of the inactive peptide NT-pro-BNP in PAH. This study
      examined the value of serial NT-pro-BNP measurements in predicting prognosis PAH.
      We retrospectively analyzed all available NT-pro-BNP plasma samples in 198
      patients who were diagnosed with World Health Organization group I PAH from
      January 2002 through January 2009. At time of diagnosis median NT-pro-BNP levels
      were significantly different between survivors (610 pg/ml, range 6 to 8,714) and
      nonsurvivors (2,609 pg/ml, range 28 to 9,828, p <0.001). In addition, NT-pro-BNP
      was significantly associated (p <0.001) with other parameters of disease severity
      (6-minute walking distance, functional class). Receiver operating curve analysis
      identified >=1,256 pg/ml as the optimal NT-pro-BNP cutoff for predicting
      mortality at time of diagnosis. Serial measurements allowed calculation of
      baseline NT-pro-BNP (i.e., intercept obtained by back-extrapolation of
      concentration-time graph), providing a better discrimination between survivors
      and nonsurvivors than NT-pro-BNP at time of diagnosis alone (p = 0.010).
      Furthermore, a decrease of NT-pro-BNP of >15%/year was associated with survival.
      In conclusion, a serum NT-pro-BNP level >=1,256 pg/ml at time of diagnosis
      identifies poor outcome in patients with PAH. In addition, a decrease in NT-pro
      BNP of >15%/year is associated with survival in PAH.

PMID- 21890090
TI  - Myocardial ischemia and ventricular tachycardia on continuous
      electrocardiographic monitoring and risk of cardiovascular outcomes after non-ST
      segment elevation acute coronary syndrome (from the MERLIN-TIMI 36 Trial).
AB  - Among patients with non-ST-segment elevation acute coronary syndromes, recurrent
      ischemia and ventricular arrhythmias detected on continuous electrocardiographic
      monitoring remain common events that are associated with worse outcomes. The
      relative clinical significance of both events together is not well described. We
      determined the risk associated with ischemia (>=1 mm ST depression lasting >=1
      minutes) and ventricular tachycardia (VT) (>=4 beats) detected on 7-day
      continuous electrocardiographic monitoring in 6,355 patients with non-ST-segment
      elevation acute coronary syndromes from the Metabolic Efficiency with Ranolazine
      for Less Ischemia in Non-ST-elevation Acute Coronary Syndrome-Thrombolysis In
      Myocardial Infarction (MERLIN-TIMI) 36 trial. The patients were categorized into
      4 groups according to the presence or absence of VT and ischemia. Cardiovascular
      death, sudden cardiac death (SCD), myocardial infarction, and recurrent ischemia
      were assessed during a median follow-up of 348 days. A total of 60.0% patients
      had no VT or ischemia, 20.0% had VT alone, 14.7% had ischemia alone, and 5.3% had
      both. The patients with either VT or ischemia were at increased risk of
      cardiovascular outcomes. The combination of ischemia and VT identified a
      particularly high-risk population for cardiovascular death (10.1% vs 3.0%, p
      <0.001), SCD (7.8% vs 0.9%, p <0.001), and myocardial infarction (15.4% vs 6.2%,
      p <0.001) compared to patients with neither. The addition of arrhythmia and
      ischemia significantly improved the clinical model for predicting cardiovascular
      death or SCD (p <0.001). In patients with both ischemia and VT, 66.6% of SCD
      occurred within 90 days of the non-ST-segment elevation acute coronary syndromes.
      In conclusion, in >6,300 patients with non-ST-segment elevation acute coronary
      syndromes, the presence of myocardial ischemia or VT alone, and particularly in
      combination, was independently associated with poor cardiovascular outcomes and
      thus provides incremental improvement in early risk stratification.

PMID- 21890091
TI  - A propensity-matched study of the comparative effectiveness of angiotensin
      receptor blockers versus angiotensin-converting enzyme inhibitors in heart
      failure patients age >= 65 years.
AB  - The comparative effectiveness of angiotensin-converting enzyme (ACE) inhibitors
      versus angiotensin II type 1 receptor blockers (ARBs) in real-world older heart
      failure (HF) patients remains unclear. Of the 8,049 hospitalized HF patients aged
      >= 65 years discharged alive from 106 Alabama hospitals, 4,044 received discharge
      prescriptions of either ACE inhibitors (n = 3,383) or ARBs (n = 661). Propensity
      scores for ARB use, calculated for each of 4,044 patients, were used to match 655
      (99% of 661) patients receiving ARBs with 661 patients receiving ACE inhibitors.
      The assembled cohort of 655 pairs of patients was well balanced on 56 baseline
      characteristics. During >8 years of follow-up, all-cause mortality occurred in
      63% and 68% of matched patients receiving ARBs and ACE inhibitors, respectively
      (hazard ratio [HR] associated with ARB use 0.86, 95% confidence interval [CI]
      0.75 to 0.99, p = 0.031). Among the 956 matched patients with data on the left
      ventricular ejection fraction (LVEF), the association between ARB (vs ACE
      inhibitor) use was significant in only 419 patients with LVEFs >= 45% (HR 0.65,
      95% CI 0.51 to 0.84, p = 0.001) but not in the 537 patients with LVEFs < 45% (HR
      1.00, 95% CI 0.81 to 1.23, p = 0.999; p for interaction = 0.012). HRs for HF
      hospitalization associated with ARB use were 0.99 (95% CI 0.86 to 1.14, p =
      0.876) overall, 0.80 (95% CI 0.63 to 1.03, p = 0.080) in those with LVEFs >=45%,
      and 1.14 (95% CI 0.91 to 1.43, p = 0.246) in those with LVEFs <45% (p for
      interaction = 0.060). In conclusion, in older HF patients with preserved LVEFs,
      discharge prescriptions of ARBs (vs ACE inhibitors) were associated with lower
      mortality and a trend toward lower HF hospitalization, findings that need
      replication in other HF populations.

PMID- 21890092
TI  - Mode of death and hospitalization from the Second Follow-up Serial Infusions of
      Nesiritide (FUSION II) trial and comparison of clinical events committee
      adjudicated versus investigator reported outcomes.
AB  - The aim of this study was to evaluate the mode of death and hospitalizations in
      advanced heart failure (HF) patients with renal dysfunction and to examine the
      rate of concordance between events reported by the clinical events committee and
      site investigators (using case report forms) in the Second Follow-Up Serial
      Infusions of Nesiritide (FUSION II) trial. Little is known about the cause of
      death and hospitalization in patients with advanced HF. FUSION II was a
      randomized, double-blind, placebo-controlled trial evaluating outpatient
      nesiritide infusions versus placebo, with 911 patients with advanced HF (New York
      Heart Association class III or IV) and renal dysfunction enrolled. There were 151
      deaths and 1,041 hospitalizations at 24 weeks. The clinical events committee
      classified events as cardiac, renal, cardiorenal, other or noncardiovascular, or
      unknown. Kappa statistics and McNemar tests were used to assess agreement
      (overall and by individual modes of death and hospitalization indications). In
      conclusion, the most common cause of death or hospitalization was cardiac
      related, with 70% of deaths and 60% of hospitalizations due to cardiac causes.
      There was 74% agreement (26% disagreement) on cardiac cause of death (kappa =
      0.40, McNemar p = 0.001) and 75% agreement (25% disagreement) between the
      investigators and the clinical events committee on cardiac classification for
      hospitalization (kappa = 0.49, McNemar p <0.0001).

PMID- 21890093
TI  - Effect of Joint National Committee VII report on hospitalizations for
      hypertensive emergencies in the United States.
AB  - Approximately 1% to 2% of patients with hypertension will have a hypertensive
      emergency at some time in their life. However, no data are available on the
      frequency of hospitalizations for a hypertensive emergency after the publication
      of the Seventh Joint National Committee (JNC7) on the prevention, detection,
      evaluation, and treatment of high blood pressure. We sought to explore the
      changes in the frequency of hospitalizations and in-hospital mortality for
      hypertensive emergencies before and after the JNC7 report. Using the Nationwide
      Inpatient Sample from 2000 to 2007, adult patients (aged >=18 years) who were
      hospitalized with a diagnosis of a hypertensive emergency were identified through
      appropriate "International Classification of Diseases, 9th revision, Clinical
      Modification" codes. A total of 456,259 hospitalizations with the diagnosis of
      hypertensive emergency occurred from the start of calendar year 2000 to the end
      of calendar year 2007. After adjusting for the United States census for 2000 and
      American Community Survey estimates for 2007 for adults, the frequency of
      hospitalizations with a hypertensive emergency increased in United States adults
      from 101/100,000 in 2000 to 111/100,000 in 2007, an average increase of about
      1.11%. Despite the increase in hospitalizations, the all-cause in-hospital
      mortality rate decreased from 2.8% in the pre-JNC7 era to 2.6% in the post-JNC7
      era (odds ratio 0.91, 95% confidence interval 0.86 to 0.96). In conclusion, the
      results of the present study have shown that although the number of patients with
      hypertensive emergency increased from 2000 to 2007, the mortality rates decreased
      significantly after the JNC7 guidelines.

PMID- 21890095
TI  - Cervical endometriosis: clinical character and management experience in a 27-year
      span.
AB  - OBJECTIVE: The purpose of this study was to analyze the clinicopathologic
      characters and explore the possible cause of cervical endometriosis. STUDY
      DESIGN: By retrospective review, among 13,566 cases of endometriosis that had
      been treated in our hospital, 33 cases of pathologically proven cervical
      endometriosis were extracted. RESULTS: Of 33 cases, 17 women had abnormal vaginal
      bleeding or visible cervical lesions; the other 16 women had no obvious clinical
      manifestations but were diagnosed retrospectively on histopathologic reports.
      Vaginal delivery or curettage procedures had occurred in 84.8% of patients. Only
      2 patients had undergone cervical surgery of cryotherapy or electric excision.
      Seven cases were misdiagnosed before final surgery with the primary suspicion of
      cervical myoma, inflammatory cyst, cervical polyp, uterine submucous myoma,
      melanoma or melanin mole, and cervical cancer. Surgical treatment was performed
      for all symptomatic patients. No recurrence was seen. CONCLUSION: Cervical
      endometriosis should be distinguished from other benign or malignant cervical
      lesions. Surgical excision is suggested for symptomatic patients.

PMID- 21890096
TI  - Association between preterm delivery and subsequent C-reactive protein: a
      retrospective cohort study.
AB  - OBJECTIVE: We sought to determine whether giving birth preterm is associated with
      raised maternal C-reactive protein (CRP) in later life and whether the
      association is specific to indicated or spontaneous delivery. STUDY DESIGN: This
      was a Scotland-wide retrospective cohort study of 1124 women who had a first
      pregnancy resulting in a singleton, liveborn infant delivered between 24-43
      weeks' gestation. Linear regression analysis was used to examine the association
      between preterm delivery and subsequent CRP concentration. RESULTS: The
      difference in CRP between women who delivered term and preterm was nonsignificant
      on univariate analysis (beta coefficient 0.04, P = .18) but was statistically
      significant following adjustment for potential confounders (beta coefficient
      0.05, P < .05). On subgroup analysis the association was specific to women who
      had had indicated preterm delivery (unadjusted beta coefficient 0.09, P < .01;
      adjusted beta coefficient 0.09, P < .01). CONCLUSION: Women who undergo indicated
      preterm delivery are at increased risk of raised CRP in later life.

PMID- 21890097
TI  - Comment on: "de rerum natura" by Josef Fischer, MD.

PMID- 21890098
TI  - Frailty predicts increased hospital and six-month healthcare cost following
      colorectal surgery in older adults.
AB  - BACKGROUND: The purpose of this study was to determine the relationship of
      frailty and 6-month postoperative costs. METHODS: Subjects aged >= 65 years
      undergoing elective colorectal operations were enrolled in a prospective
      observational study. Frailty was assessed by a validated measure of function,
      cognition, nutrition, comorbidity burden, and geriatric syndromes. Frailty was
      quantified by summing the number of positive characteristics in each subject.
      RESULTS: Sixty subjects (mean age, 75 +/- 8 years) were studied. Inpatient
      mortality was 2% (n = 1). Overall, 40% of subjects (n = 24) were considered
      nonfrail, 22% (n = 13) were prefrail, and 38% (n = 22) were frail. With advancing
      frailty, hospital costs increased (P < .001) and costs from discharge to 6-months
      increased (P < .001). Higher degrees of frailty were related to increased rates
      of discharge institutionalization (P < .001) and 30-day readmission (P = .044).
      CONCLUSIONS: A simple, brief preoperative frailty assessment accurately forecasts
      increased surgical hospital costs and postdischarge to 6-month healthcare costs
      after colorectal operations in older adults.

PMID- 21890099
TI  - Mediastinal goiter: a comprehensive study of 60 consecutive cases with special
      emphasis on identifying predictors of malignancy and sternotomy.
AB  - BACKGROUND: We describe the clinical characteristics of patients with mediastinal
      goiter and our principles in surgical management of this pathology; we also
      identify the predictive factors of malignancy, sternotomy, and posterior
      mediastinal extension. METHODS: We conducted a retrospective chart review of 60
      patients with mediastinal goiter who underwent surgical intervention. RESULTS:
      Major perioperative complications were recurrent laryngeal nerve sacrifice (3.3%)
      and vagus nerve sacrifice (1.7%). A total of 12.7% of cases were malignant. The
      presence of dysphonia increased the likelihood of malignancy (P = .02), and
      malignancy was associated with a significant increase in sternotomy (P = .04) and
      nerve sacrifice (P < .001) during surgery. A history of thyroidectomy was a
      predictive factor for extension of the tumor to the posterior mediastinum (P =
      .02). CONCLUSIONS: Presenting with dysphonia is a predictor of malignancy that
      necessitates careful surgical planning because malignancy is associated with an
      increase in nerve injury and sternotomy during surgery.

PMID- 21890100
TI  - Response to: topical gentamicin does not provide any additional anastomotic
      strength when combined with fibrin glue.

PMID- 21890101
TI  - Response to: topical gentamicin does not provide any additional anastomotic
      strength when combined with fibrin glue.

PMID- 21890102
TI  - Increased skin autofluorescence after colorectal operation reflects surgical
      stress and postoperative outcome.
AB  - BACKGROUND: Abdominal surgery is a major oxidative stress effector. The increase
      in oxidative stress has been related to postoperative complications. Oxidative
      stress leads to the formation and accumulation of oxidation protein end products,
      which exhibit autofluorescence (AF) and induce inflammatory reactions. METHODS:
      Skin AF was assessed perioperatively in 40 consecutive colorectal surgery
      patients until discharge. Duration of surgery, estimated blood loss, and urinary
      production per hour were analyzed as measures of surgical stress. The clinical
      occurrence of anastomotic leakage, systemic infections, and cardiopulmonary
      complications within 30 days of surgery were analyzed. RESULTS: A perioperative
      increase in skin AF of 19 +/- .2% was observed. Duration of operation and blood
      loss were independently associated with the perioperative increase in skin AF.
      Skin AF correlated with C-reactive protein levels postoperatively. American
      Society of Anesthesiologists classification, duration of operation, and
      preoperative and perioperative increases in AF were independently associated with
      postoperative complications. CONCLUSIONS: This is the first study to demonstrate
      an association between skin AF and surgical stress and outcomes, which may rate
      the condition of a patient after operation.

PMID- 21890103
TI  - Is aviation a good model to study human errors in health care?

PMID- 21890104
TI  - [A non-fatal Nerium oleander self-poisoning: case report and discussion].
AB  - Nerium oleander is potentially lethal plants after ingestion. We report a case of
      poisoning by these plants. Our patient complained of nausea, vomiting, and
      diarrhoea. He had bradycardia during first twelve hours. He was discharge after 3
      days. All parts of these plants are toxic and contain a variety of cardiac
      glycosides including oleandrin. In most cases, clinical management of poisoning
      by N. oleander involves administration of activated charcoal and supportive care.
      Digoxin specific Fab fragments are an effective treatment.

PMID- 21890105
TI  - [Contribution of closed mitral commissurotomy in the surgery of rheumatic mitral
      stenosis].
AB  - The objective of this work was to study the indications, techniques and results
      of closed heart mitral commissurotomy in patients with rheumatic mitral stenosis
      in Morocco. METHODS: All patients who had undergone closed heart mitral
      commissurotomy for rheumatic mitral stenosis, operated between 1999 and 2008 were
      collected in this study. Mitral stenosis was diagnosed and evaluated using
      Doppler echocardiography. Patients with commissural calcification, severe mitral
      regurgitation, and surgical tricuspid or aortic valvular disease were excluded
      from this study. RESULTS: Six hundred and twenty-five patients have been
      collected. 62.2% were young with an age between 18 and 35 years and 491 (78.8%)
      were female. Seventy-nine percent of patients had stage III or IV NYHA and were
      in sinus regular rhythm. The closed heart mitral commissurotomy was performed for
      all patients through a left thoracotomy using either digital or dual dilatation.
      The mitral area was significantly increased postoperatively to 2.11 +/- 0.32 with
      100% opening of the anterior commissure, while the posterior commissure was
      opened only for 93.7% of patients. There were nine perioperative deaths (4.9%)
      and all patients who died had severe mitral stenosis (<0.8 cm(2)) with an
      elevated systolic pulmonary artery pressure (>60 mmHg). CONCLUSION: The closed
      heart mitral commissurotomy provides excellent results in young patients with
      rheumatic mitral stenosis.

PMID- 21890106
TI  - [An exceptional cause of pacemaker dysfunction].
AB  - Twiddler syndrome is a very rare and surprising complication of pacemaker
      treatment. We report the case of a woman with psychiatric disease who presented
      two cardiac arrests due to loss of ventricular capture. Finally, pacemaker
      retropectoral implantation resolves the problem.

PMID- 21890107
TI  - Preferential recruitment of bone marrow-derived cells to rat palatal wounds but
      not to skin wounds.
AB  - OBJECTIVE: To investigate the contribution of bone marrow-derived cells to oral
      mucosa wounds and skin wounds. BACKGROUND: Bone marrow-derived cells are known to
      contribute to wound healing, and are able to differentiate in many different
      tissue-specific cell types. As wound healing in oral mucosa generally proceeds
      faster and with less scarring than in skin, we compared the bone marrow
      contribution in these two tissues. DESIGN: Bone marrow cells from GFP-transgenic
      rats were transplanted to irradiated wild-type rats. After recovery, 4-mm wounds
      were made in the mucoperiosteum or the skin. Two weeks later, wound tissue with
      adjacent normal tissue was stained for GFP-positive cells, myofibroblasts (a
      smooth muscle actin), activated fibroblasts (HSP47), and myeloid cells (CD68).
      RESULTS: The fraction of GFP-positive cells in unwounded skin (19%) was larger
      than in unwounded mucoperiosteum (0.7%). Upon wounding, the fraction of GFP
      positive cells in mucoperiosteum increased (8.1%), whilst it was unchanged in
      skin. About 7% of the myofibroblasts in both wounds were GFP-positive, 10% of the
      activated fibroblasts, and 25% of the myeloid cells. CONCLUSIONS: The results
      indicate that bone marrow-derived cells are preferentially recruited to wounded
      oral mucosa but not to wounded skin. This might be related to the larger healing
      potential of oral mucosa.

PMID- 21890108
TI  - Relationship between glycemic subsets and generalized chronic periodontitis in
      type 2 diabetic Brazilian subjects.
AB  - OBJECTIVE: The aim of the present study was to evaluate the relationship between
      glycemic subsets and clinical periodontal conditions in type 2 diabetic
      Brazilians with generalized chronic periodontitis. DESIGN: Ninety-one Brazilians
      with type 2 DM and generalized chronic periodontitis were involved in this study.
      The clinical examination included full-mouth assessment of plaque index (PI),
      bleeding on probing (BoP), probing depth (PD), suppuration (SUP), clinical
      attachment level (CAL) and number of remaining teeth. Blood analyses were carried
      out for glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG). The
      relationship between the extent of periodontitis, defined as the percentage of
      sites with PD and CAL>=5 mm, and glycemic parameters were also analysed. In
      addition, clinical parameters were compared amongst four (HbA1c levels <=7.5%,
      7.6-9%, 9.1-11% and >11%) and two (<9% and >=9%) glycemic subsets. RESULTS: The
      frequency of uncontrolled diabetic subjects (HbA1c>7.5%) was higher than well
      controlled subjects (HbA1c<=7.5%). Amongst the clinical parameters evaluated,
      only PI was positively correlated with the levels of HbA1c and FPG (p<0.05). The
      number of remaining teeth was negatively associated with the levels of HbA1c
      (p<0.05). In addition, PI was significantly higher in subjects presenting HbA1c
      levels >11% and >=9% than those with HbA1c levels <=7.5% and <9%, respectively
      (p<0.05). CONCLUSION: Although an increased frequency of the subjects with
      generalized chronic periodontitis included presented type 2 uncontrolled DM, a
      dose-response relationship between the severity and extension of periodontitis
      and the glycemic control was not established in these subjects.

PMID- 21890109
TI  - Differential sensitivity to psychostimulants across prefrontal cognitive tasks:
      differential involvement of noradrenergic alpha1 - and alpha2-receptors.
AB  - BACKGROUND: Psychostimulants improve a variety of cognitive and behavioral
      processes in patients with attention-deficit/hyperactivity disorder (ADHD).
      Limited observations suggest a potentially different dose-sensitivity of
      prefrontal cortex (PFC)-dependent function (narrow inverted-U-shaped dose
      response curves) versus classroom/overt behavior (broad inverted U) in children
      with ADHD. Recent work in rodents demonstrates that methylphenidate (MPH;
      Ritalin) elicits a narrow inverted-U-shaped improvement in performance in PFC
      dependent tests of working memory. The current studies first tested the
      hypothesis that PFC-dependent tasks, in general, display narrow dose sensitivity
      to the beneficial actions of MPH. METHODS: The effects of varying doses of MPH
      were examined on performance of rats in two tests of PFC-dependent cognition,
      sustained attention and attentional set shifting. Additionally, the effect of
      pretreatment with the alpha1-antagonist prazosin (.5 mg/kg) on MPH-induced
      improvement in sustained attention was examined. RESULTS: MPH produced a broad
      inverted-U-shaped facilitation of sustained attention and attentional set
      shifting. Prior research indicates alpha1-receptors impair, whereas alpha2
      receptors improve, working memory. In contrast, attentional set shifting is
      improved with alpha1-receptor activation, whereas alpha2-receptors exert minimal
      effects in this task. Given the similar dose sensitivity of sustained attention
      and attentional set-shifting tasks, additional studies examined whether alpha1
      receptors promote sustained attention, similar to attentional set shifting. In
      these studies, MPH-induced improvement in sustained attention was abolished by
      alpha1-receptor blockade. CONCLUSIONS: PFC-dependent processes display
      differential sensitivity to the cognition-enhancing actions of psychostimulants
      that are linked to the differential involvement of alpha1- versus alpha2
      receptors in these processes. These observations have significant preclinical and
      clinical implications.

PMID- 21890110
TI  - A time-dependent history of mood disorders in a murine model of neuropathic pain.
AB  - BACKGROUND: Chronic pain is clinically associated with the development of
      affective disorders. However, studies in animal models of neuropathic pain are
      contradictory and the relationship with mood disorders remains unclear. In this
      study, we aimed to characterize the affective consequences of neuropathic pain
      over time and to study potential underlying mechanisms. METHODS: Neuropathic pain
      was induced by inserting a polyethylene cuff around the main branch of the right
      sciatic nerve in C57BL/6J mice. Anxiety- and depression-related behaviors were
      assessed over 2 months, using a battery of tests, such as elevated plus maze,
      marble burying, novelty suppressed feeding, splash test, and forced swimming
      test. Plasma corticosterone levels were assessed by radioimmunoassay. We also
      investigated changes in cyclic adenosine monophosphate response element (CRE)
      activity using CRE-LacZ transgenic mice. RESULTS: Mice developed anxiety-related
      behavior 4 weeks after induction of the neuropathy, and depression-related
      behaviors were observed after 6 to 8 weeks. Control and neuropathic mice did not
      differ for basal or stress-induced levels of corticosterone or for hypothalamic
      pituitary-adrenal axis negative feedback. After 8 weeks, the CRE-mediated
      activity decreased in the outer granule layer of dentate gyrus of neuropathic
      mice but not in the amygdala or in the anterior cingulate cortex. CONCLUSIONS:
      Our results demonstrate that the affective consequences of neuropathic pain
      evolve over time, independently from the hypothalamic-pituitary-adrenal axis,
      which remains unaffected. CRE-mediated transcription within a limbic structure
      was altered at later time points of the neuropathy. These experiments provide a
      preclinical model to study time-dependent development of mood disorders and the
      underlying mechanism in a neuropathic pain context.

PMID- 21890112
TI  - Diverse excitatory and inhibitory synaptic plasticity outcomes in complex
      horizontal circuits near a functional border of adult neocortex.
AB  - The primary somatosensory cortex (SI) is topographically organized into a map of
      the body. This organization is dynamic, undergoing experience-dependent
      modifications throughout life. It has been hypothesized that excitatory and
      inhibitory synaptic plasticity of horizontal intracortical connections
      contributes to functional reorganization. However, very little is known about
      synaptic plasticity of these connections; particularly the characteristics of
      inhibitory synaptic plasticity, its relationship to excitatory synaptic
      plasticity, and their relationship to the functional organization of the cortex.
      To investigate this, we located the border between the forepaw and lower jaw
      representation of SI in vivo, and used whole cell-patch electrophysiology to
      record post-synaptic excitatory and inhibitory currents in complex horizontal
      connections in vitro. Connections that remained within the representation
      (continuous) and those that crossed from one representation to another
      (discontinuous) were stimulated differentially, allowing us to examine
      differences associated with the border. To induce synaptic plasticity, tetanic
      stimulation was applied to either continuous or discontinuous pathways. Tetanic
      stimulation induced diverse forms of excitatory and inhibitory synaptic
      plasticity, with LTP dominating for excitation and LTD dominating for inhibition.
      The border did not restrict plasticity in either case. In contrast, tetanization
      elicited LTP of monosynaptic inhibitory responses in continuous, but not
      discontinuous connections. These results demonstrate that continuous and
      discontinuous pathways are capable of diverse synaptic plasticity responses that
      are differentially inducible. Furthermore, continuous connections can undergo
      monosynaptic inhibitory LTP, independent of excitatory drive onto interneurons.
      Thus, coordinated excitatory and inhibitory synaptic plasticity of horizontal
      connections are capable of contributing to functional reorganization.

PMID- 21890111
TI  - Multivariate searchlight classification of structural magnetic resonance imaging
      in children and adolescents with autism.
AB  - BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopmental disorders with
      a prevalence of nearly 1:100. Structural imaging studies point to disruptions in
      multiple brain areas, yet the precise neuroanatomical nature of these disruptions
      remains unclear. Characterization of brain structural differences in children
      with ASD is critical for development of biomarkers that may eventually be used to
      improve diagnosis and monitor response to treatment. METHODS: We use voxel-based
      morphometry along with a novel multivariate pattern analysis approach and
      searchlight algorithm to classify structural magnetic resonance imaging data
      acquired from 24 children and adolescents with autism and 24 age-, gender-, and
      IQ-matched neurotypical participants. RESULTS: Despite modest voxel-based
      morphometry differences, multivariate pattern analysis revealed that the groups
      could be distinguished with accuracies of approximately 90% based on gray matter
      in the posterior cingulate cortex, medial prefrontal cortex, and bilateral medial
      temporal lobes-regions within the default mode network. Abnormalities in the
      posterior cingulate cortex were associated with impaired Autism Diagnostic
      Interview communication scores. Gray matter in additional prefrontal, lateral
      temporal, and subcortical structures also discriminated between groups with
      accuracies between 81% and 90%. White matter in the inferior fronto-occipital and
      superior longitudinal fasciculi, and the genu and splenium of the corpus
      callosum, achieved up to 85% classification accuracy. CONCLUSIONS: Multiple brain
      regions, including those belonging to the default mode network, exhibit aberrant
      structural organization in children with autism. Brain-based biomarkers derived
      from structural magnetic resonance imaging data may contribute to identification
      of the neuroanatomical basis of symptom heterogeneity and to the development of
      targeted early interventions.

PMID- 21890113
TI  - Alteration of protein expression profile following voluntary exercise in the
      perilesional cortex of rats with focal cerebral infarction.
AB  - Identification of functional molecules in the brain related to improvement of the
      degree of paralysis or increase of activities will contribute to establishing a
      new treatment strategy for stroke rehabilitation. Hence, protein expression
      changes in the cerebral cortex of rat groups with/without voluntary exercise
      using a running wheel after cerebral infarction were examined in this study.
      Motor performance measured by the accelerated rotarod test and alteration of
      protein expression using antibody microarray analysis comprised 725 different
      antibodies in the cerebral cortex adjacent to infarction area were examined. In
      behavioral evaluation, the mean latency until falling from the rotating rod in
      the group with voluntary exercise for five days was significantly longer than
      that in the group without voluntary exercise. In protein expression profile,
      fifteen proteins showed significant quantitative changes after voluntary exercise
      for five days compared to rats without exercise. Up-regulated proteins were
      involved in protein phosphorylation, stress response, cell structure and
      motility, DNA replication and neurogenesis (11 proteins). In contrast, down
      regulated proteins were related to apoptosis, cell adhesion and proteolysis (4
      proteins). Additional protein expression analysis showed that both growth
      associated protein 43 (GAP43) and phosphorylated serine41 GAP43 (pSer41-GAP43)
      were significantly increased. These protein expression changes may be related to
      the underlying mechanisms of exercise-induced paralysis recovery, that is,
      neurite formation, and remodeling of synaptic connections may be through the
      interaction of NGF, calmodulin, PKC and GAP43. In the present study at least some
      of the participation of modulators associated with the improvement of paralysis
      might be detected.

PMID- 21890115
TI  - The association of testosterone, sleep, and sexual function in men and women.
AB  - Testosterone has been the focus of several investigations and review studies in
      males, but few have addressed its effects on sleep and sexual function, despite
      evidence of its androgenic effects on circadian activity in both sexes. Studies
      have been conducted to understand how sleeping increases (and how waking
      decreases) testosterone levels and how this rhythm can be related to sexual
      function. This review addresses the inter-relationships among testosterone,
      sexual function and sleep, including sleep-disordered breathing in both sexes,
      specifically its effects related to sleep deprivation. In addition, hormonal
      changes in testosterone that occur in the gonadal and adrenal axis with
      obstructive sleep apnea and other conditions of chronic sleep deprivation, and
      which consequently affect sexual life, have also been explored. Nevertheless,
      hormone-associated sleep disruptions occur across a lifetime, particularly in
      women. The association between endogenous testosterone and sex, sleep and sleep
      disturbances is discussed, including the results of clinical trials as well as
      animal model studies. Evidence of possible pathophysiological mechanisms
      underlying this relationship is also described. Unraveling the associations of
      sex steroid hormone concentrations with sleep and sexual function may have
      clinical implications, as sleep loss reduces testosterone levels in males, and
      low sex steroid hormone concentrations have been associated with sexual
      dysfunction.

PMID- 21890114
TI  - Information analysis of posterior canal afferents in the turtle, Trachemys
      scripta elegans.
AB  - We have used sinusoidal and band-limited Gaussian noise stimuli along with
      information measures to characterize the linear and non-linear responses of
      morpho-physiologically identified posterior canal (PC) afferents and to examine
      the relationship between mutual information rate and other physiological
      parameters. Our major findings are: 1) spike generation in most PC afferents is
      effectively a stochastic renewal process, and spontaneous discharges are fully
      characterized by their first order statistics; 2) a regular discharge, as
      measured by normalized coefficient of variation (cv*), reduces intrinsic noise in
      afferent discharges at frequencies below the mean firing rate; 3) coherence and
      mutual information rates, calculated from responses to band-limited Gaussian
      noise, are jointly determined by gain and intrinsic noise (discharge regularity),
      the two major determinants of signal to noise ratio in the afferent response; 4)
      measures of optimal non-linear encoding were only moderately greater than optimal
      linear encoding, indicating that linear stimulus encoding is limited primarily by
      internal noise rather than by non-linearities; and 5) a leaky integrate and fire
      model reproduces these results and supports the suggestion that the combination
      of high discharge regularity and high discharge rates serves to extend the linear
      encoding range of afferents to higher frequencies. These results provide a
      framework for future assessments of afferent encoding of signals generated during
      natural head movements and for comparison with coding strategies used by other
      sensory systems. This article is part of a Special Issue entitled: Neural Coding.

PMID- 21890116
TI  - Synergic effect of diazepam and muscimol via presynaptic GABA(A) receptors on
      glutamatergic evoked EPSCs.
AB  - We investigated the functional roles of diazepam (DZP) at presynaptic GABA(A)
      receptors on glutamatergic nerve terminals in contributing to glutamatergic
      transmission evoked by single and/or paired-pulse focal electrical stimulation.
      In mechanically dissociated rat hippocampal CA3 neurons with adherent
      glutamatergic nerve terminals (boutons), namely 'synaptic bouton' preparation,
      action potential-evoked excitatory postsynaptic currents (eEPSCs) were recorded
      using conventional whole-cell patch configuration under voltage-clamp condition.
      Selective activation of presynaptic GABA(A) receptors by muscimol (3-30MUM)
      induced presynaptic inhibition: i.e. the decrease of amplitude and increase of
      failure rate (Rf) and paired-pulse ratio (PPR) of eEPSCs which are sensitive to
      bicuculline. DZP (10-100MUM) also induced such presynaptic inhibition, but the
      bicuculline-insensitive effects were caused by inhibition of both voltage
      dependent Na(+) and Ca(2+) channels. Muscimol (0.01-0.3MUM) or DZP (0.1-3MUM)
      itself did not induce any currents at the low concentration used. However,
      simultaneous application of muscimol and DZP at low concentrations induced a
      significant bicuculline-sensitive presynaptic inhibition. Marked desensitization
      of presynaptic inhibition was also caused by muscimol at higher concentrations
      than 10MUM. The results suggest that in vivo conditions, activation of
      presynaptic GABA(A) receptors could be readily available with a tiny amount of
      DZP.

PMID- 21890117
TI  - Involvement of the anterior thalamic radiation in boys with high functioning
      autism spectrum disorders: a Diffusion Tensor Imaging study.
AB  - BACKGROUND: Autism has been hypothesized to reflect neuronal disconnection.
      Several recent reports implicate the key thalamic relay nuclei and cortico
      thalamic connectivity in the pathophysiology of autism. Accordingly, we aimed to
      focus on evaluating the integrity of the thalamic radiation and sought to
      replicate prior white matter findings in Korean boys with high-functioning autism
      spectrum disorders (ASD) using Diffusion Tensor Imaging (DTI). METHODS: We
      compared fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity
      (AD) and radial diffusivity (RD) in 17 boys with ASD and 17 typically developing
      controls in the anterior thalamic radiation (ATR), superior thalamic radiation
      (STR), posterior thalamic radiation (PTR), corpus callosum (CC), uncinate
      fasciculus (UF) and inferior longitudinal fasciculus (ILF). RESULTS: The two
      groups were group-matched on age, IQ, handedness and head circumference. In whole
      brain voxel-wise analyses, FA was significantly reduced and MD was significantly
      increased in the right ATR, CC, and left UF in subjects with ASD (p<0.05,
      corrected). We found significantly lower FA in right and left ATR, CC, left UF
      and right and left ILF and significantly higher MD values of the CC in the ASD
      group in region of interest-based analyses. We also observed significantly higher
      RD values of right and left ATR, CC, left UF, left ILF in subjects with ASD
      compared to typically developing boys and significantly lower AD values of both
      ILF. Right ATR and right UF FA was significantly negatively correlated with total
      SRS score within the ASD group (r=-.56, p=.02). CONCLUSIONS: Our preliminary
      findings support evidence implicating disturbances in the thalamo-frontal
      connections in autism. These findings highlight the role of hypoconnectivity
      between the frontal cortex and thalamus in ASD.

PMID- 21890118
TI  - Optimizing estimation of hemispheric dominance for language using magnetic source
      imaging.
AB  - The efficacy of magnetoencephalography (MEG) as an alternative to invasive
      methods for investigating the cortical representation of language has been
      explored in several studies. Recently, studies comparing MEG to the gold standard
      Wada procedure have found inconsistent and often less-than accurate estimates of
      laterality across various MEG studies. Here we attempted to address this issue
      among normal right-handed adults (N=12) by supplementing a well-established MEG
      protocol involving word recognition and the single dipole method with a sentence
      comprehension task and a beamformer approach localizing neural oscillations.
      Beamformer analysis of word recognition and sentence comprehension tasks revealed
      a desynchronization in the 10-18Hz range, localized to the temporo-parietal
      cortices. Inspection of individual profiles of localized desynchronization (10
      18Hz) revealed left hemispheric dominance in 91.7% and 83.3% of individuals
      during the word recognition and sentence comprehension tasks, respectively. In
      contrast, single dipole analysis yielded lower estimates, such that activity in
      temporal language regions was left-lateralized in 66.7% and 58.3% of individuals
      during word recognition and sentence comprehension, respectively. The results
      obtained from the word recognition task and localization of oscillatory activity
      using a beamformer appear to be in line with general estimates of left
      hemispheric dominance for language in normal right-handed individuals.
      Furthermore, the current findings support the growing notion that changes in
      neural oscillations underlie critical components of linguistic processing.

PMID- 21890119
TI  - Reciprocal projections in hierarchically organized evolvable neural circuits
      affect EEG-like signals.
AB  - Modular architecture is a hallmark of many brain circuits. In the cerebral
      cortex, in particular, it has been observed that reciprocal connections are often
      present between functionally interconnected areas that are hierarchically
      organized. We investigate the effect of reciprocal connections in a network of
      modules of simulated spiking neurons. The neural activity is recorded by means of
      virtual electrodes and EEG-like signals, called electrochipograms (EChG),
      analyzed by time- and frequency-domain methods. A major feature of our approach
      is the implementation of important bio-inspired processes that affect the
      connectivity within a neural module: synaptogenesis, cell death, spike-timing
      dependent plasticity and synaptic pruning. These bio-inspired processes drive the
      build-up of auto-associative links within each module, which generate an areal
      activity, recorded by EChG, that reflect the changes in the corresponding
      functional connectivity within and between neuronal modules. We found that
      circuits with intra-layer reciprocal projections exhibited enhanced stimulus
      locked response. We show evidence that all networks of modules are able to
      process and maintain patterns of activity associated with the stimulus after its
      offset. The presence of feedback and horizontal projections was necessary to
      evoke cross-layer coherence in bursts of -frequency at regular intervals. These
      findings bring new insights to the understanding of the relation between the
      functional organization of neural circuits and the electrophysiological signals
      generated by large cell assemblies. This article is part of a Special Issue
      entitled "Neural Coding".

PMID- 21890120
TI  - Lesions and reversible inactivation of the dorsolateral caudate-putamen impair
      cocaine-primed reinstatement to cocaine-seeking in rats.
AB  - Recent evidence suggests that cocaine addiction may involve progressive drug
      induced neuroplasticity of the dorsal striatum. Here, we examined the effects of
      a) dorsolateral caudate putamen (dlCPu) lesions on cocaine self-administration,
      extinction of responding, and subsequent reinstatement to cocaine-seeking, and b)
      reversible inactivation of the dlCPu with GABA receptor agonists (baclofen and
      muscimol) immediately prior to reinstatement testing. Male, Sprague-Dawley rats
      self-administered cocaine (0.2mg/50MUl infusion, i.v.) along an FR1 schedule in
      daily 2h sessions for 10days, whereby lever presses resulted in cocaine infusions
      and presentation of a paired light-tone stimulus complex. After 14days of
      abstinence, animals were returned to the self-administration chamber and lever
      responding was recorded, but had no programmed consequences (relapse test).
      Animals then underwent daily extinction, followed by reinstatement tests in the
      presence of the conditioned cues, after a cocaine priming injection (10mg/kg), or
      cues+cocaine prime. Lesions of the dlCPu failed to affect responding during self
      administration, extinction, relapse, or cued-induced reinstatement. However,
      lesioned animals showed reduced cocaine-seeking during cocaine-primed
      reinstatement as compared to sham controls. Furthermore, reversible inactivation
      of the dlCPu significantly impaired both cocaine-primed and cocaine-primed+cue
      induced reinstatement. These results demonstrate the critical involvement of the
      dlCPu in cocaine-primed reinstatement, perhaps via chronic drug-induced changes
      in the interoceptive effects of cocaine that impact drug-seeking.

PMID- 21890121
TI  - Immunohistochemical studies on disabled-2 protein in the spinal cords of rats
      with experimental autoimmune encephalomyelitis.
AB  - Disabled-2 (Dab-2), an adaptor protein of transforming growth factor beta (TGF
      beta) signaling, was studied in the spinal cords of rats with experimental
      autoimmune encephalomyelitis (EAE) to evaluate the possible involvement of Dab-2
      in the pathogenesis of EAE using Western blot and immunohistochemical analyses.
      Western blot analysis showed that two isoforms (p96 kDa and p67 kDa) of Dab-2
      were detected in the spinal cords of rats used as controls. Both isoforms of Dab
      2 were significantly elevated in the EAE spinal cord at the peak stage of EAE
      (P<0.05) and declined at the recovery stage. However, only the p96 kDa isoform
      was markedly phosphorylated in the EAE spinal cord. Immunohistochemistry showed
      that Dab-2 and p-Dab-2 were detected in some vascular endothelial cells, glial
      cells, and some neurons in the rat spinal cords of normal and immunized CFA-alone
      controls. In EAE lesions, Dab-2 and p-Dab-2 were immunodetected in some
      inflammatory cells (mainly in ED1-positive macrophages and R73-positive T cells),
      while the enhanced immunoreactivity of Dab-2 in spinal cord cells suggested
      constitutive expression. Additionally, TGF-beta1 immunoreactivity showed a
      similar expression pattern of Dab-2 in EAE lesions. These findings suggest that
      Dab-2 is transiently upregulated and phosphorylated (particularly the p96 kDa
      isoform) in EAE, a CNS autoimmune disease, and may be involved in TGF-beta
      signaling.

PMID- 21890122
TI  - [Assessment of the surgical risk of 1,000 consecutive episodes using the POSSUM
      system. Comparison between elective and emergency gastrointestinal surgery].
AB  - INTRODUCTION: The aim of the present study was to assess the predictive capacity
      of the POSSUM system in a Spanish university hospital, and to determine its
      behaviour in elective gastrointestinal surgery and compare it with emergency
      gastrointestinal surgery (operation < 24 hours). PATIENTS AND METHOD: A total of
      1,000 surgical episodes corresponding to 909 patients who required hospital
      admission, operated on under general or loco-regional anaesthesia, either in the
      elective (n= 547 episodes) or the emergency setting (n= 453), were included in
      the study. RESULTS: The overall morbidity was 31.9% (32.8% in elective surgery;
      30.7% in emergency surgery). The discriminatory capacity of the POSSUM scale,
      evaluated using receiver operating characteristic (ROC) curves, was higher for
      the Portsmouth variant of mortality (Area Under the Curve [AUC] = 0,92) than for
      morbidity (AUC= 0,74). The goodness of fit between the expected values using the
      POSSUM scale and those observed was reduced for morbidity (Hosmer-Lemeshow [H-L]
      = 164.1; p< 0.05). The POSSUM scale predicted a higher number of deaths than
      those observed, although the Portsmouth variant was better at predicting
      mortality. The goodness of fit for morbidity was better for elective
      gastrointestinal surgery (H-L= 27.7) than emergency gastrointestinal surgery (H
      L= 177.3). The logistic regression analysis identified (besides the estimated
      risk using the POSSUM scale itself), surgical complexity, surgery type (elective,
      emergency), and age of patient, as significant predictive factors of morbidity
      and mortality. CONCLUSIONS: In a Spanish university hospital, the POSSUM system
      adequately predicts morbidity risk in elective gastrointestinal surgery, and over
      estimates morbidity risk in emergency gastrointestinal surgery.

PMID- 21890123
TI  - Reporting and management of breast lesions detected using MRI.
AB  - Magnetic resonance imaging (MRI) is the most accurate technique for diagnosing
      and delineating the extent of both invasive and in-situ breast cancer and is
      increasingly being used as part of the preoperative work-up to assess the local
      extent of disease. It is proving invaluable in providing information that allows
      successful single-stage surgery. An inevitable consequence of the high
      sensitivity of MRI is that it will identify additional lesions that may or may
      not represent significant extra disease. This may complicate and delay the
      preoperative process. This paper outlines a strategy for managing MRI-detected
      lesions to optimize the benefits of breast MRI as a local staging tool while
      minimizing the false-positive diagnoses. It discusses the importance of good
      technique to reduce the number of indeterminate lesions. Methods to refine the
      patient pathway to minimize delays are discussed. The format of MRI reporting is
      discussed in detail as is the usefulness of discussion of cases at
      multidisciplinary meetings. Illustrative cases are used to clarify the points
      made.

PMID- 21890124
TI  - Variability in photos of the same face.
AB  - Psychological studies of face recognition have typically ignored within-person
      variation in appearance, instead emphasising differences between individuals.
      Studies typically assume that a photograph adequately captures a person's
      appearance, and for that reason most studies use just one, or a small number of
      photos per person. Here we show that photographs are not consistent indicators of
      facial appearance because they are blind to within-person variability. Crucially,
      this within-person variability is often very large compared to the differences
      between people. To investigate variability in photos of the same face, we
      collected images from the internet to sample a realistic range for each
      individual. In Experiments 1 and 2, unfamiliar viewers perceived images of the
      same person as being different individuals, while familiar viewers perfectly
      identified the same photos. In Experiment 3, multiple photographs of any
      individual formed a continuum of good to bad likeness, which was highly sensitive
      to familiarity. Finally, in Experiment 4, we found that within-person variability
      exceeded between-person variability in attractiveness. These observations are
      critical to our understanding of face processing, because they suggest that a key
      component of face processing has been ignored. As well as its theoretical
      significance, this scale of variability has important practical implications. For
      example, our findings suggest that face photographs are unsuitable as proof of
      identity.

PMID- 21890125
TI  - Escaping capture: bilingualism modulates distraction from working memory.
AB  - We ask whether bilingualism aids cognitive control over the inadvertent guidance
      of visual attention from working memory and from bottom-up cueing. We compare
      highly-proficient Catalan-Spanish bilinguals with Spanish monolinguals in three
      visual search conditions. In the working memory (WM) condition, attention was
      driven in a top-down fashion by irrelevant objects held in WM. In the Identify
      condition, attention was driven in a bottom-up fashion by visual priming. In the
      Singleton condition, attention was driven in a bottom-up fashion by including a
      unique distracting object in the search array. The results showed that bilinguals
      were overall faster than monolinguals in the three conditions, replicating
      previous findings that bilinguals can be more efficient than monolinguals in the
      deployment of attention. Interestingly, bilinguals were less captured by
      irrelevant information held in WM but were equally affected by visual priming and
      unique singletons in the search displays. These observations suggest that
      bilingualism aids top-down WM-mediated guidance of attention, facilitating
      processes that keep separate representations in WM from representations that
      guide visual attention. In contrast, bottom-up attentional capture by salient yet
      unrelated input operates similarly in bilinguals and monolinguals.

PMID- 21890126
TI  - Automatic colposcopy video tissue classification using higher order entropy-based
      image registration.
AB  - Colposcopy is a well-established method to detect and diagnose intraepithelial
      lesions and uterine cervical cancer in early stages. During the exam color and
      texture changes are induced by the application of a contrast agent (e.g.3-5%
      acetic acid solution or iodine). Our aim is to densely quantify the change in the
      acetowhite decay level for a sequence of images captured during a colposcopy exam
      to help the physician in his diagnosis providing new tools that overcome
      subjectivity and improve reproducibility. As the change in acetowhite decay level
      must be calculated from the same tissue point in all images, we present an
      elastic image registration scheme able to compensate patient, camera and tissue
      movement robustly in cervical images. The image registration is based on a novel
      multi-feature entropy similarity criterion. Temporal features are then extracted
      using the color properties of the aligned image sequence and a dual compartment
      tissue model of the cervix. An example of the use of the temporal features for
      pixel-wise classification is presented and the results are compared against
      ground truth histopathological annotations.

PMID- 21890127
TI  - [Wernicke encephalopathy in alcoholic patients].
AB  - A 67-year old male was brought to the hospital by his family because he had been
      suffering from somnolence, bradypsychia and gait disturbance for one week. He
      lived alone, reported an ethanol intake higher than 100-120 g/day. His diet was
      limited in quality and amount. The physical examination showed stigmata of
      chronic liver disease. The neurological exam revealed right-side cerebellar
      tremor, bilateral dysmetria and gait ataxia as well as hyporeflexia in the lower
      limbs. He was diagnosed of Wernicke encephalopathy. How should this patient be
      evaluated and treated?

PMID- 21890128
TI  - [Venous thromboembolic disease and May-Thurner syndrome].

PMID- 21890129
TI  - Melatonin protects human spermatozoa from apoptosis via melatonin receptor- and
      extracellular signal-regulated kinase-mediated pathways.

PMID- 21890130
TI  - Triple ultrasound markers including fetal cardiac activity are related to
      miscarriage risk.
AB  - OBJECTIVE: To identify early ultrasound markers in pregnant patients that predict
      a favorable pregnancy outcome. DESIGN: Retrospective case-control study. SETTING:
      Infertility patients in fertility clinic. PATIENT(S): 1051 women with early
      pregnancies conceived after fertility treatment. INTERVENTION(S): None. MAIN
      OUTCOME MEASURE(S): Ongoing pregnancy >20 weeks' gestation. RESULT(S): Ongoing
      pregnancy rate was 90.5% for those pregnancies having early fetal cardiac
      activity (odds ratio [OR] = 66.5). Gestational sac diameter >=12 mm was
      associated with ongoing pregnancy rate of 91.9%. Small gestational sac diameter,
      <8 mm, was associated with high miscarriage rate, 85.3%. Ongoing pregnancy rates
      for yolk sac diameter <2 mm, 2-6 mm, and >6 mm were 20%, 89.2%, and 20%,
      respectively (OR = 33.1, 2-6 vs <2 mm; OR = 33.1, 2-6 vs >6 mm). Ongoing
      pregnancy rate was 94% when all three markers were present. CONCLUSION(S): On
      postconception days 33-36, gestational sac diameter >=12 mm, yolk sac diameter 2
      6 mm, and the presence of fetal cardiac activity were favorable markers.

PMID- 21890131
TI  - Assessment of 1,2-propanediol (PrOH) genotoxicity on mouse oocytes by comet
      assay.
AB  - OBJECTIVE: To assess the genotoxicity of 1,2-propanediol (PrOH) on mouse oocytes
      by comet assay. DESIGN: In vitro assay using murine model. SETTING:
      Biogenotoxicology research laboratory. ANIMAL(S): CD1 female mice.
      INTERVENTION(S): Three 40-oocyte groups were exposed to different PrOH
      concentrations (5%, 7.5%, and 15%). Each concentration was tested during both
      long and short exposures (1-2 hours and 1-5 minutes) in comparison with control
      groups. DNA damage was evaluated by a single-cell gel electrophoresis assay, also
      called "comet assay," and analyzed with Komet software. MAIN OUTCOME MEASURE(S):
      DNA damage was quantified as Olive tail moment (OTM). Interpretation was done on
      OTM with the use of chi(2). RESULT(S): High PrOH concentrations (7.5% and 15%)
      induced significant DNA damage on mouse oocytes. The OTM chi(2) values were 4.16
      +/- 0.40 and 6.80 +/- 0.4 with 7.5% PrOH at 1 and 2 hours, respectively, 24.35 +/
      1.60 with 15% at 1 hour, and for 2h at 15% the DNA damage was too drastic to
      calculate OTM chi(2). After 1 and 5 minutes, the OTM chi(2) values were,
      respectively, 5.19 +/- 0.26 and 6.06 +/- 0.42 with 7.5%, and 7.53 +/- 0.33 and
      16.81 +/- 0.67 with 15%. CONCLUSION(S): High concentrations of PrOH (7.5% and
      15%) induced significant DNA damage on mouse oocytes, whatever the exposure
      duration. These results should be interpreted with caution, because additional
      data are needed to evaluate PrOH genotoxicity and DNA oocyte reparation after
      exposure to high PrOH concentrations.

PMID- 21890132
TI  - Subsequent alterations in the contractile property of the vas deferens according
      to duration of spermatic cord torsion.
AB  - OBJECTIVE: To determine whether twisting of the ipsilateral vas deferens results
      in alteration of its contractility. DESIGN: Experimental study. SETTING:
      University animal lab. ANIMAL(S): 24 male Wistar rats. INTERVENTION(S): All the
      rats in the experimental groups underwent spermatic cord torsion. Durations of
      torsion were 45 minutes, 3 hours, and 24 hours in groups 2, 3, and 4,
      respectively. In groups 2 and 3, subgroups b were created to evaluate late
      effects using in vitro pharmacological techniques. MAIN OUTCOME MEASURE(S): The
      contractility of the vas deferens was evaluated in groups 1, 2a, 3a, and 4 right
      after and in groups 2b and 3b 48 hours after the initial operation. RESULT(S):
      Group 4 and subgroups 2b and 3a had significantly diminished responses compared
      with the control group, whereas in subgroups 2a and 3b, the responses to
      noradrenaline and to single-pulse field stimulation were not significantly
      different. CONCLUSION(S): The impairment of contractility with the twisting of
      the vas deferens might be another factor responsible for subfertility,
      particularly that related to sperm transport. The unfavorable late change in
      short duration of torsion may be the result of either ischemia and reperfusion
      injury or sympathetic overactivation in the acute period of torsion.

PMID- 21890133
TI  - Cryopreservation of blastocysts is the most feasible strategy in good responder
      patients.
AB  - OBJECTIVE: To assess on which day to cryopreserve and transfer thawed embryos in
      good-responder patients by comparing the cycle outcomes of day 3 transfers vs
      blastocysts formed through extended culture before or after cryopreservation.
      DESIGN: Retrospective clinical study. SETTING: Private IVF center. PATIENT(S):
      Frozen-thawed cycles (n = 2,531) who had ETs at day 3, 5, and 6 and post-thawed
      extended culture of day 3 until day 5 or 6. INTERVENTION(S): None. MAIN OUTCOME
      MEASURE(S): Primary outcomes were implantation and delivery rates. Secondary
      outcomes were clinical pregnancy and miscarriage rates. RESULT(S): In thawing
      cycles, embryos developing to blastocysts on day 5 through extended culture
      before or after cryopreservation yielded higher rates of implantation (51.1% and
      51.3%, respectively), clinical pregnancy (69.9% and 62.2%, respectively), and
      delivery per thawing cycle (56.7% and 51%, respectively) accompanied by lower
      miscarriage rates (15.2%, 16.4%, respectively) compared with day 3 transfers
      (28.3%, 55.3%, 42.5%, 20.1%, respectively). Late-developing embryos formed before
      or after cryopreservation resulted in compromised implantation (44.7% and 44.2%,
      respectively), clinical pregnancy (59.9% and 45.9%, respectively), delivery per
      thawing cycle (42.8% and 32.4%, respectively) and higher miscarriage rates (25.7%
      and 23.5%, respectively) than day 5 embryos. CONCLUSION(S): The feasible strategy
      in good responder patients appears to be the cryopreservation of blastocysts in
      the fresh cycle. Retardation in development results in a compromised outcome
      because of reduced inherent capacity of embryos.

PMID- 21890134
TI  - Couples with unexplained subfertility and unfavorable prognosis: a randomized
      pilot trial comparing the effectiveness of in vitro fertilization with elective
      single embryo transfer versus intrauterine insemination with controlled ovarian
      stimulation.
AB  - OBJECTIVE: To evaluate the effectiveness of IVF with elective single embryo
      transfer (IVF-eSET) vs. IUI with controlled ovarian stimulation (IUI-COS) as an
      alternative treatment to reduce the risk for a multiple pregnancy. DESIGN:
      Randomized pilot trial. SETTING: Three academic and six teaching hospitals in the
      Netherlands. PATIENT(S): Couples with unexplained or mild male subfertility and
      an unfavorable prognosis for natural conception. INTERVENTION(S): One cycle of
      IVF-eSET or three cycles of IUI-COS. MAIN OUTCOME MEASURE(S): Ongoing pregnancy
      per couple. RESULT(S): We randomly allocated 116 women to IVF-eSET (n = 58) or
      IUI-COH (n = 58). There were 14 ongoing pregnancies (24%) in the IVF-eSET group
      and 12 pregnancies (21%) in the IUI-COS group (relative ratio 1.17; 95%
      confidence interval 0.60-2.30). There were two twin pregnancies in the IVF-eSET
      group (14%) and two twin pregnancies and one triplet pregnancy in the IUI-COH
      group (25%). CONCLUSION(S): In patients with unexplained or mild male
      subfertility and a poor prognosis for natural conception, one cycle of IVF-eSET
      might be as effective as three cycles of IUI-COS as primary treatment. Elective
      single embryo transfer does not seem an effective strategy in preventing multiple
      pregnancies in this particular population. In the future a strict SET policy
      (i.e., compulsory SET) might be an option. Our trial provides evidence for the
      feasibility and highlights the importance of a large definitive trial to
      determine the effectiveness and side effects of both strategies.

PMID- 21890135
TI  - Esophageal squamous papilloma with tentacular processes.

PMID- 21890136
TI  - Pulmonary and peritoneal inflammatory findings in transgastric NOTES compared
      with laparoscopy: pooled analysis from randomized porcine survival studies.
AB  - BACKGROUND: Laparoscopy, which is a minimally invasive surgery, is associated
      with decreased peritoneal adhesions and inflammatory response compared with
      laparotomy. OBJECTIVE: To evaluate whether natural orifice transluminal
      endoscopic surgery (NOTES) leads to an attenuated peritoneal response compared
      with laparoscopy. DESIGN: Pooled histologic analysis from 2 randomized porcine
      trials. SETTING: Laboratory. INTERVENTION: Histologic analysis of swine
      undergoing diagnostic laparoscopy, diagnostic NOTES peritoneoscopy, NOTES with
      transgastric mesh placement, or diagnostic endoscopy (no gastrotomy) followed by
      laparoscopic mesh placement. MAIN OUTCOME MEASUREMENTS: The presence and grade of
      inflammation in necropsy specimens of lung, liver, and spleen as reviewed by a
      blinded veterinary pathologist. RESULTS: Four NOTES mesh animals exhibited mesh
      infections at necropsy. Tissue from 48 swine were available for analysis.
      Pulmonary inflammation, liver fibrosis, and spleen capsulitis were the primary
      findings. No difference was seen in the incidence of each finding among groups.
      The severity of the pulmonary inflammation in the laparoscopy group was
      significantly higher than in the NOTES groups. The NOTES mesh group exhibited
      significantly more severe liver fibrosis and spleen capsulitis. There was no
      difference between clinical behavior, serum white blood cell count, or peritoneal
      white blood cell count among groups in either study. Intra-abdominal pressures
      during NOTES were lower than during laparoscopy. LIMITATIONS: Pooled analysis of
      2 separate studies. CONCLUSION: More severe pulmonary inflammation was found in
      animals undergoing longer laparoscopic procedures with higher intra-abdominal
      pressures. Intraperitoneal inflammation was most significant with transgastric
      mesh placement, likely caused by infections.

PMID- 21890138
TI  - Identification and partial characterization of C-glycosylflavone markers in Asian
      plant dyes using liquid chromatography-tandem mass spectrometry.
AB  - Flavonoids in the grasses (Poaceae family), Arthraxon hispidus (Thunb.) Makino
      and Miscanthus tinctorius (Steudel) Hackel have long histories of use for
      producing yellow dyes in Japan and China, but up to now there have been no
      analytical procedures for characterizing the dye components in textiles dyed with
      these materials. LC-MS analysis of plant material and of silk dyed with extracts
      of these plants shows the presence, primarily, of flavonoid C-glycosides, three
      of which have been tentatively identified as luteolin 8-C-rhamnoside, apigenin 8
      C-rhamnoside and luteolin 8-C-(4-ketorhamnoside). Two of these compounds,
      luteolin 8-C-rhamnoside (M=432), apigenin 8-C-rhamnoside (M=416), along with the
      previously known tricin (M=330) and several other flavonoids that appear in
      varying amounts, serve as unique markers for identifying A. hispidus and M.
      tinctorius as the source of yellow dyes in textiles. Using this information, we
      have been able to identify grass-derived dyes in Japanese textiles dated to the
      Nara and Heian periods. However, due to the high variability in the amounts of
      various flavonoid components, our goal of distinguishing between the two plant
      sources remains elusive.

PMID- 21890137
TI  - Outcome of conjoined tendon and coracoacromial ligament transfer for the
      treatment of chronic type V acromioclavicular joint separation.
AB  - BACKGROUND: Numerous surgical methods are used to treat acromioclavicular (AC)
      joint dislocations, and an anatomical reconstruction using a free tendon graft
      has attracted considerable attention, particularly for chronic cases. The purpose
      of this study was to introduce the results of lateral half conjoined tendon
      (LHCT) and coracoacromial ligament (CAL) transfer for chronic type V injuries.
      MATERIALS AND METHODS: A retrospective evaluation was performed on the clinical
      and radiographic outcomes of the 12 patients who underwent LHCT and CAL transfer
      for chronic type V AC injuries and had been followed for 2 years postoperatively.
      All 12 patients were males with a mean age of 37.3 +/- 7.7 years (range: 26-49
      years) at surgery. The causes of the injury were traffic accidents (five), falls
      (three) and sports injuries (four). The mean time elapsed between trauma and
      surgery was 12.5 +/- 5.4 weeks (range: 7-22 weeks). RESULTS: No reduction loss
      was observed at the final follow-up. The postoperative coracoclavicular (CC)
      distance was 8.9 +/- 1.6mm, which represented a significant improvement versus
      the preoperative status (20.3 +/- 3.0mm; p < 0.001), and no significant
      difference was observed between the injured and uninjured contralateral sides
      (8.7 +/- 0.8mm), postoperatively (p = 0.619). The temporary use of a Steinman pin
      for AC fixation did not cause any complications. On the other hand, there were
      eight cases of mild radiographic arthrosis at the AC joint and two cases of
      heterotopic ossification of the CC space, although neither affected the
      functional outcomes. The mean modified UCLA score was 18.5 +/- 2.1 (range: 12
      20), which represented an excellent result in 11 of the 12 cases. The single case
      with a poorer postoperative score had a pre-existing brachial plexus injury.
      CONCLUSIONS: Despite the small study cohort, the results of LHCT and CAL transfer
      in chronic type V AC separation are promising. CAL transfer alone has been shown
      to be biomechanically insufficient for an AC reconstruction, particularly in
      chronic situations. The advantage of LHCT transfer is that it does not require a
      distant donor site or incur the costs of an allograft or implant.

PMID- 21890139
TI  - Detailed molecular characterization of castor oil ethoxylates by liquid
      chromatography multistage mass spectrometry.
AB  - The molecular characterization of castor oil ethoxylates (CASEOs) was studied by
      reverse-phase liquid chromatography (RPLC) mass spectrometry (MS) and multistage
      mass spectrometry (MS(n)). The developed RPLC method allowed the separation of
      the various CASEO components, and especially, the baseline separation of multiple
      nominal isobars (same nominal mass) and isomers (same exact mass). MS and MS(n)
      were used for the determination and structure elucidation of various structures
      and for the discrimination of the isobars and isomers. Different ionization
      techniques and adduct ions were also tested for optimization of the MS detection
      and the MS(n) fragmentation. A unique fragmentation pathway of ricinoleic acid is
      proposed, which can be used as a marker of the polymerization process and the
      topology of ethoxylation in the CASEO. In addition, characteristic neutral losses
      of ricinoleic acid reveal its (terminal or internal) position in the molecule.

PMID- 21890140
TI  - Protein UTLC-MALDI-MS using thin films of submicrometer silica particles.
AB  - Slides for ultra thin-layer chromatography (UTLC) were made by coating nonporous
      silica particles, chemically modified with polyacrylamide, as 15 MUm films on
      glass or silicon. Three proteins, myoglobin, cytochrome c and lysozyme, are
      nearly baseline resolved by the mechanism of hydrophilic interaction
      chromatography. A plate height as low as 3 MUm, with 3900 plates, is observed in
      14 mm. Varying silica particle diameter among 900, 700 and 350 nm showed that
      decreasing particle diameter slightly improves resolution but slows the
      separation. Matrix-assisted laser desorption/ionization (MALDI)-MS of the
      proteins after separation is demonstrated by wicking sufficient sinapinic acid
      into the separation medium.

PMID- 21890141
TI  - A discontinuous Galerkin method to solve chromatographic models.
AB  - This article proposes a discontinuous Galerkin method for solving model equations
      describing isothermal non-reactive and reactive chromatography. The models
      contain a system of convection-diffusion-reaction partial differential equations
      with dominated convective terms. The suggested method has capability to capture
      sharp discontinuities and narrow peaks of the elution profiles. The accuracy of
      the method can be improved by introducing additional nodes in the same solution
      element and, hence, avoids the expansion of mesh stencils normally encountered in
      the high order finite volume schemes. Thus, the method can be uniformly applied
      up to boundary cells without loosing accuracy. The method is robust and well
      suited for large-scale time-dependent simulations of chromatographic processes
      where accuracy is highly demanding. Several test problems of isothermal non
      reactive and reactive chromatographic processes are presented. The results of the
      current method are validated against flux-limiting finite volume schemes. The
      numerical results verify the efficiency and accuracy of the investigated method.
      The proposed scheme gives more resolved solutions than the high resolution finite
      volume schemes.

PMID- 21890142
TI  - Aptamer-targeted magnetic nanospheres as a solid-phase extraction sorbent for
      determination of ochratoxin A in food samples.
AB  - A sorbent based on the aptamer for ochratoxin A was immobilized onto magnetic
      nanospheres (MNS) and used to develop a magnetic solid-phase extraction procedure
      to clean up food samples in conjunction with high-performance liquid
      chromatography separation and fluorescence detection. Specific retention of
      ochratoxin A by the sorbent was demonstrated, and the capacity of the MNS-aptamer
      sorbent was determined. The efficacy of this new approach was successfully
      evaluated through comparison with solid-phase extraction on commercial C18
      cartridge. Several different food samples fortified in the range of with 2.5-50
      MUg/kg yielded mean recoveries from 67% to 90%, respectively. Finally, this
      oligosorbent was applied to the selective extraction of ochratoxin A from
      unfortified food samples.

PMID- 21890144
TI  - Use of isopycnic plots in designing operations of supercritical fluid
      chromatography. III: reason for the low column efficiency in the critical region.
AB  - This paper discusses the origins of efficiency loss in supercritical fluid
      chromatography (SFC) when analyses are carried out in the low pressure
      supercritical region of carbon-dioxide, close to its critical point. Recent
      publications have shown strong evidence of radial thermal heterogeneity inside an
      SFC column and suggested that it leads to peak-shape distortion and greatly
      reduces the column efficiency. We demonstrate that the physico-chemical
      properties of CO(2) close to the critical point are such that formation of
      thermal heterogeneity inside the column is highly probable and could cause the
      observed efficiency loss. Consideration of isopycnic plots of CO(2) permits clear
      identification of the problematic region and explains why these properties of
      CO(2) are primarily responsible for the often perplexing efficiency losses taking
      place during the SFC operations.

PMID- 21890143
TI  - Protein adsorption and transport in dextran-modified ion-exchange media. III.
      Effects of resin charge density and dextran content on adsorption and
      intraparticle uptake.
AB  - Custom-synthesized variants of the commercial Capto S resin were used to examine
      the effects of resin charge density and dextran content on protein adsorption and
      intraparticle uptake. For the small protein lysozyme, resin charge density had
      the greatest effect on equilibrium capacity, consistent with calculations
      suggesting that lysozyme capacity should be limited by the available charge on
      the resin. Isocratic retention data and confocal microscopy imaging for this
      protein revealed a consistent ordering of the resins linking stronger protein
      resin interactions with higher static capacities but slower intraparticle uptake
      rates over the range of properties studied. For the larger protein lactoferrin,
      it was found that increasing dextran content led to increased protein exclusion
      from the dextran layer, but that increasing resin charge density helped overcome
      the exclusion, presumably due to the increased electrostatic attraction between
      the resin and protein. Collectively examining the lysozyme and lactoferrin data
      along with information from previous studies suggests that a trade-off in
      maximizing dynamic capacities should exist between static capacities that
      increase to a finite extent with increased resin charge density and uptake rates
      that decrease with increased charge density. Column breakthrough data for
      lysozyme and lactoferrin appear to support the hypothesis, though it appears that
      whether a resin charge density is low or high must be considered in relation to
      the protein charge density. Using these trends, this work could be useful in
      guiding resin selection or design.

PMID- 21890145
TI  - A sensitive and simple ultra-high-performance-liquid chromatography-tandem mass
      spectrometry based method for the quantification of D-amino acids in body fluids.
AB  - D-Amino acids are increasingly being recognized as important signaling molecules
      in mammals, including humans. D-Serine and D-aspartate are believed to act as
      signaling molecules in the central nervous system. Interestingly, several other D
      amino acids also occur in human plasma, but very little is currently known
      regarding their function and origin. Abnormal levels of D-amino acids have been
      implicated in the pathogenesis of different diseases, including schizophrenia and
      amyotrophic lateral sclerosis (ALS), indicating that D-amino acid levels hold
      potential as diagnostic markers. Research into the biological functions of D
      amino acids is hindered, however, by the lack of sufficiently sensitive, high
      throughput analytical methods. In particular, the interference of large amounts
      of L-amino acids in biological samples and the low concentrations of D-amino
      acids are challenging. In this paper, we compared 7 different chiral
      derivatization agents for the analysis of D-amino acids and show that the chiral
      reagent (S)-NIFE offers outstanding performance in terms of sensitivity and
      enantioselectivity. An UPLC-MS/MS based method for the quantification of D-amino
      acids human biological fluids was then developed using (S)-NIFE. Baseline
      separation (R(s)>2.45) was achieved for the isomers of all 19 chiral
      proteinogenic amino acids. The limit of detection was <1 nM for all amino acids
      except d-alanine (1.98 nM), d-methionine (1.18 nM) and d-asparagine (5.15 nM).
      For measurements in human plasma, cerebrospinal fluid and urine, the accuracy
      ranged between 85% and 107%. The intra-assay and inter-assay were both <16% RSD
      for these three different matrices. Importantly, the method does not suffer from
      spontaneous racemization during sample preparation and derivatization. Using the
      described method, D-amino acid levels in human cerebrospinal fluid, plasma and
      urine were measured.

PMID- 21890146
TI  - Size tuning of luminescent silicon nanoparticles with meso-porous silicon
      membranes.
AB  - Size tuning of silicon (Si) nanoparticles (NPs) with the use of meso-porous
      silicon (meso-PS) free-standing layers is reported for the first time.
      Accumulation of Si NPs inside the membrane pores during the filtering process (NP
      transport through the meso-PS) leads to an auto-filtration effect (called Si-by
      Si (SBS) filtration) allowing more efficient size selection of the NPs. General
      complex fractal shape and surface chemistry of the whole porous network, layer
      thickness as well as a given initial NP size dispersion determine final size of
      the NPs in the filtered solution. Moreover, quantum of step-like NP size
      increasing equal to 0.12 nm was found.

PMID- 21890148
TI  - Safe at home?

PMID- 21890147
TI  - Markers of severe vaso-occlusive painful episode frequency in children and
      adolescents with sickle cell anemia.
AB  - OBJECTIVE: To identify factors associated with frequent severe vaso-occlusive
      pain crises in a contemporary pediatric cohort of patients with sickle cell
      anemia (SCA) enrolled in a prospective study of pulmonary hypertension and the
      hypoxic response in sickle cell disease. STUDY DESIGN: Clinical and laboratory
      characteristics of children with SCA who had >=3 severe pain crises requiring
      health care in the preceding year were compared with those of subjects with <3
      such episodes. RESULTS: Seventy-five children (20%) reported >=3 severe pain
      episodes in the preceding year, and 232 (61%) had none. Frequent pain episodes
      were associated with older age (OR, 1.2; 95% CI, 1.1-1.3; P < .0001), alpha
      thalassemia trait (OR 3.5; 1.6-6.7; P = .002), higher median hemoglobin (OR 1.7;
      95% CI: 1.2-2.4; P < .003), and lower lactate dehydrogenase concentration (OR
      1.82; 95% CI: 1.07-3.11; P = .027). Children with high pain frequency also had an
      increased iron burden (serum ferritin, 480 vs 198 MUg/L; P = .006) and higher
      median tricuspid regurgitation jet velocity (2.41 vs 2.31 m/s; P = .001). Neither
      hydroxyurea use nor fetal hemoglobin levels were significantly different
      according to severe pain history. CONCLUSIONS: In our cohort of children with
      SCA, increasing age was associated with higher frequency of severe pain episodes
      as were alpha-thalassemia, iron overload, higher hemoglobin and lower lactate
      dehydrogenase concentration, and higher tricuspid regurgitation velocity.

PMID- 21890150
TI  - In vitro comparison of different mechanical prostheses suitable for replacement
      of the systemic atrioventricular valve in children.
AB  - OBJECTIVE: The aim of the present study was to compare the hydrodynamics of 4
      different mechanical prostheses fitting the atrioventricular annulus in children.
      METHODS: We tested different inverted aortic prostheses with a prosthesis-annulus
      relationship in the mitral chamber of the Sheffield pulse duplicator (Department
      of Medical Physics and Clinical Engineering, Royal Hallamshire Hospital,
      Sheffield, UK), analyzed by comparing the prosthetic housing diameter and the
      predicted annulus diameter based on body surface area (0.8 and 1 m(2)
      corresponding to an annulus diameter of 18.8-20.2 mm). The On-X 19 (On-X Life
      Technologies, Inc, Austin, Tex), SJM Regent 19 (St Jude Medical Inc, St Paul,
      Minn), Sorin Overline 18 (Sorin Biomedica, Saluggia, Italy), and Medtronic
      Advantage Supra 19 (Medtronic Inc, Minneapolis, Minn) valves with a housing
      diameter of 19 to 20 mm were hydrodynamically compared. The tests were carried
      out at increasing pulse rate of 72, 80, 100, and 120 beats/min for a stroke
      volume of 20 and 30 mL. Therefore, cardiac output ranged from 1.44 to 3.6 L/min.
      RESULTS: Regardless of the pulse rate and stroke volume, the Medtronic Advantage
      Supra valve showed the highest mean diastolic pressure difference at each cardiac
      output (P < .05). The mean gradients were significantly lower for the Sorin
      Overline valve regardless of the cardiac output, stroke volume, and pulse rate (P
      < .05). The effective orifice areas observed followed exactly the same behavior:
      the lowest for the Medtronic Advantage Supra valve and the highest for the Sorin
      Overline valve. The Sorin Overline valve showed the highest closure volumes (P <
      .05), and the On-X prosthesis showed the highest leakage volumes (P < .05). The
      Sorin Overline valve had the highest total regurgitant volume (P < .05), and the
      Medtronic Advantage Supra valve had the lowest total regurgitant volume (P <
      .05). The On-X valve showed the highest total energy loss regardless of the pulse
      rate at 20 mL of stroke volume, which was comparable to the SJM Regent and Sorin
      Overline valves at increased stroke volume. The Medtronic Advantage Supra valve
      showed the lowest total energy loss regardless of cardiac outputs (P < .05).
      CONCLUSIONS: This hydrodynamic evaluation model allowed us to compare the
      efficiency of currently available valve prostheses suitable for atrioventricular
      replacement in children. Among these prostheses, the Sorin Overline valve showed
      the best diastolic performance. On the other hand, for total energy loss, the
      Medtronic Advantage Supra valve demonstrated excellent performance.

PMID- 21890149
TI  - Maternal smoking during pregnancy and anger temperament among adult offspring.
AB  - Maternal smoking during pregnancy has been consistently associated with
      aggressive behaviors among offspring across the life course. We posit that anger,
      as a precedent of aggression, may have mediated the association. The current
      study examines the relation between maternal smoking during pregnancy and anger
      proneness among the adult offspring. Participants were 611 adult offspring (ages
      38-48 years) of mothers enrolled in the Collaborative Perinatal Project between
      1959 and 1966 in Boston and Providence. Information on maternal smoking during
      pregnancy was collected during prenatal visits. Spielberger's trait anger scale
      was used to measure anger proneness which has two components: anger temperament
      and angry reaction. Results from the full sample analyses showed that offspring
      whose mother smoked one pack or more per day on average scored 1.7 higher in
      anger temperament T scores in comparison to offspring whose mother never smoked
      during pregnancy (beta=1.7, 95% Confidence Interval (CI): 0.1, 3.2). The fixed
      effects analyses among siblings that accounted for more confounding found a
      greater effect of around one standard deviation increase in anger temperament T
      scores corresponding to maternal smoking of one pack or more (beta=7.4, 95% CI:
      0.5, 14.4). We did not observe an association of maternal smoking during
      pregnancy with offspring angry reaction or other negative emotions including
      anxiety and depression. We concluded that prenatal exposure to heavy cigarette
      smoke was associated with an increased level of anger temperament, a stable
      personality trait that may carry the influence of prenatal smoking through the
      life course.

PMID- 21890151
TI  - An exploratory study of boarding home sanctions and compliance in Washington
      State.
AB  - States vary in enforcement systems that monitor the quality of care in
      residential boarding homes. The growing number of people seeking long-term care
      services in boarding homes requires regulatory systems that are effective in
      quality assurance enforcement. This 6 year retrospective study describes the
      characteristics of 601 sanctioned and nonsanctioned homes in the state of
      Washington and evaluates the effectiveness of enforcement actions such as
      intermediate sanctions on future boarding home compliance. The intermediate
      sanctions evaluated are stop placement of admissions, civil fines, and conditions
      placed on licenses. Boarding homes that were sanctioned tended to be homes that
      were for-profit and had governmental contracts for Medicaid services. Homes that
      remained sanctioned throughout the 6 year study tended to be homes that were
      individual ownership corporations, had smaller numbers of licensed beds, and did
      not provide nursing services. Intermediate sanctions were found to vary in
      effectiveness. Conditions placed on licenses were the most effective intermediate
      sanction, and civil fines the least effective. Higher citation numbers and the
      most severe level of complaint types were found to be predictors of becoming a
      sanctioned boarding home.

PMID- 21890152
TI  - Improvement of the nutritional quality of foods as a public health tool.
AB  - OBJECTIVES: To assess the potential contribution of improving the nutritional
      quality of processed foods on individuals' nutritional intake and food supply.
      This paper also discusses the means to encourage firms to implement these
      reformulations, particularly in public/private partnerships. STUDY DESIGN: The
      French Observatory of Food Quality was created by the Government for the
      quantification and follow-up of food reformulation by the food industry. This
      nutritional composition database on branded products was matched with two
      consumption databases: TNS Kantar Worldpanel, which provides details on
      quantities bought and food expenditures; and INCA 2, an individuals' food
      consumption survey completed by the French Food Safety Agency. Three food groups
      were considered: breakfast cereals (355 items in 2008), biscuits and pastries
      (1805 items in 2008), and bread-based products (620 items in 2009). METHODS:
      First, the variability in nutrient composition within food categories was
      determined, which made it possible to consider several food composition
      modification scenarios within each category. The formulation of the food items
      with the lowest nutritional quality was modified to three different levels to
      improve the overall level of quality in a given category. Second, the quantities
      of sugars, fat, fibre and sodium delivered to the French market through breakfast
      cereals, biscuits, pastries and bread-based products were calculated for each
      scenario. Finally, the distribution of individuals' nutrient consumption from the
      three food groups among the French population was assessed. RESULTS: These
      scenarios generated important improvements of 1-22% (increase in the amount of
      fibre or decrease in the amounts of sugars, fat and sodium delivered to the
      market), depending on the scenario, the food group and the nutrient considered.
      Improvement of the products with the lowest nutritional quality would also lead
      to significant variation in individuals' nutrient consumption for the average
      adult and child consumers of the three groups (range 4.2-18.8%, depending on the
      scenario, the food group and the nutrient considered). CONCLUSION: Encouraging
      the reformulation of foods, especially for products with the lowest nutritional
      quality in each category of processed foods, is a worthy target for health policy
      makers. The methodology presented in this paper provides information for
      negotiations between policy makers and firms to quantify commitments in terms of
      their potential impacts on individuals' nutrient intake, and to check that the
      firms' commitments are actually met.

PMID- 21890154
TI  - A multicancer-like syndrome in a dog characterized by p53 and cell cycle
      checkpoint kinase 2 (CHK2) mutations and sirtuin gene (SIRT1) down-regulation.
AB  - INTRODUCTION: We have investigated SIRT1, p53 and cell cycle-checkpoint kinase 2
      (CHK2) gene dysfunction in a dog with a multicancer syndrome-like in order to
      evaluate their potential role in the determinism of the disease and to establish
      a possible correlation between SIRT1 transcript level and p53 expression status.
      MATERIAL AND METHODS: Blood sample and tumour samples from a pure breed English
      Setter dog with different tumours were used for this study. Nucleotide sequence
      analysis was performed with a DNA autosequencer in order to examine p53 and CHK2
      mutations. In addition, the expression level of SIRT1 was quantified by Southern
      Blot analysis of Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR).
      RESULTS: Cytological examination revealed five different tumours: a cutaneous
      sebaceous epithelioma, a cutaneous mast cell tumour, a testicular Sertoli cell
      tumour, an oral malignant melanoma, and a cutaneous squamous cell carcinoma.
      Sequencing analysis revealed the presence of a nucleotide substitution, (CGG>CAG)
      exon 7 of the p53 gene in DNA from peripheral blood mononuclear cells (PBMCs) as
      well as in the melanoma; whereas the other four cancers showed the loss of the
      wild-type allele. Furthermore, CHK2 mutation at codon 311 has been identified in
      the melanoma and sebaceous epithelioma. In addition, SIRT1 cDNA expression
      decreased in all tumour samples compared to cDNA SIRT1expression level in
      peripheral blood mononuclear cells (PBMCs) in the same dog. CONCLUSIONS: These
      results suggest that the germ line mutation of the p53 gene at codon 248 might
      be, at least, one cause of the multicancer syndrome-like in our dog; furthermore,
      we show a possible correlation between SIRT1 transcript level and p53 mutations
      status. The regulatory role of SIRT1 in tumour suppressor pathways suggests that
      the net effect seen may represent both direct and indirect downstream regulation
      and it is likely to depend on the presence or absence of functional p53.

PMID- 21890155
TI  - Mathematical modeling of glioma on MRI.
AB  - The advent of Magnetic Resonance Imaging (MRI) has enabled quantification of
      glioma growth with millimetric accuracy. Thus, it is now possible to monitor the
      growth curve of tumor diameter for each patient. Mathematical modeling
      contributes to the analysis of these curves and to determining individual
      parameters characterizing tumor dynamics. We will focus on the most studied
      model, based on a proliferation-diffusion equation. We will review how this
      approach, when applied to low-grade gliomas, has enabled defining a new way to
      quantify their natural history, leading to the inclusion of tumor kinetics among
      prognostic factors. Finally, quantitative imaging coupled with mathematical
      modeling is opening new avenues in our understanding of treatment effects,
      allowing to optimize therapeutic strategies for gliomas in the near future.

PMID- 21890156
TI  - New concepts in paraneoplastic neurological syndromes.
AB  - Paraneoplastic neurological syndromes (PNS) are rare diseases defined so far by
      the presence of a neurological disorder associated with cancer in the absence of
      invasion of the nervous system by tumor cells. Discovery of circulating
      autoantibodies specific for these patients has revolutionized the diagnosis and
      understanding of these syndromes and demonstrated a role of the immune system in
      the neurological syndromes. Until recent years, we thought that these
      autoantibodies were only markers of the disease and had no role in the
      pathophysiology. The recent description of autoantibodies directed against
      membrane receptors or channels and playing a direct pathological role has
      transformed the concept of PNS. Especially, it appears that many patients may
      have a neurological syndrome and autoantibodies without cancer. This results in a
      classification based on the nature of the autoantibodies associated with
      neurological syndrome. In case of autoantibodies targeting intracellular
      antigens, cancer is almost always associated, the neurological disorders are
      mainly related to neuronal death, patients are rarely sensitive to
      immunomodulatory treatments and cellular immunity appears to play a major role.
      In contrast, patients with autoantibodies targeting membrane antigens (receptors,
      channels or receptor associated proteins) have rarely cancer, neurological
      disorders are related to a reversible neuronal dysfunction, patients are mostly
      sensitive to immunomodulatory treatments and it seems that humoral immunity and
      autoantibodies play a major role.

PMID- 21890157
TI  - [Glioblastoma in the elderly].
AB  - The incidence of malignant gliomas in the aging population of industrialized
      countries is increasing. This observation justifies an important ongoing clinical
      research effort specifically dedicated to this population. The first results of
      prospective studies have showed the interest of radiotherapy and chemotherapy
      with temozolomide. The effect of combined concomitant and adjuvant chemotherapy
      with radiotherapy is currently being evaluated in a phase III study. The likely
      beneficial effect of surgical resection needs to be formally demonstrated in this
      fragile population. Initial functional status, quality of life and concomitant
      systemic pathologies are important factors to tailor the treatment according to
      patients status.

PMID- 21890158
TI  - Brain tumor epilepsy: a reappraisal and six remaining issues to be debated.
AB  - Epilepsy associated with brain tumors presents with specific features deserving
      medical attention. Although commonly reported in patients with brain tumor,
      either as revealing mode or as a remote complication, limited knowledge is
      available regarding their epidemiology, clinical evolution, surgical outcome,
      physiopathology and treatment, providing only clues for clinical management.
      Seizures appear even more threatening for patients and caregivers, providing
      seizures could mean tumor progression and recurrence. This factor adds to the
      negative impact of epilepsy carried on quality of life measures. Pharmacotherapy
      is complicated by the use of chemotherapy and interaction between antiepileptic
      drugs and antineoplastic agents are frequent and potentially harmful. The high
      incidence of epilepsy enlights the question of prophylaxy with antiepileptic
      drugs, in patients without seizures, or during the perioperative period, and
      after surgery, when gross total resection has been achieved. This article
      attempts to provide the reader with an overview of brain tumor epilepsy in its
      specific aspects and to comment on some remaining issues.

PMID- 21890159
TI  - Wild, synanthropic and domestic hosts of Leishmania in an endemic area of
      cutaneous leishmaniasis in Minas Gerais State, Brazil.
AB  - Domestic, synanthropic and wild hosts of Leishmania spp. parasites were studied
      in an area endemic for American tegumentary leishmaniasis (ATL), specifically in
      northern Minas Gerais State, Brazil. Domestic dogs and small forest mammals are
      reservoir hosts for L. (Leishmania) infantum. However, the role that these
      animals play in the transmission cycle of the Leishmania spp. that cause
      cutaneous leishmaniasis is not well known. This study evaluated 72 rodents, 25
      marsupials and 98 domestic dogs found in two villages of the Xakriaba Indigenous
      Territory, an area of intense ATL transmission. A total of 23 dogs (23.47%) were
      shown to be positive according to at least one test; 8 dogs (8.16%) tested
      positive in a single serological test and 15 dogs (15.31%) tested positive by
      IFAT and ELISA. Eleven dogs were euthanised to allow for molecular diagnosis, of
      which nine (81.8%) tested positive by PCR for Leishmania in at least one tissue.
      Seven animals were infected only with L. (L.) infantum, whilst two displayed a
      mixed infection of L. (L.) infantum and L. (V.) braziliensis. Isoenzymatic
      characterisation identified L. (L.) infantum parasites isolated from the bone
      marrow of two dogs. Of the 97 small mammals captured, 24 tested positive for
      Leishmania by PCR. The results showed that L. (V.) braziliensis, L. (L.) infantum
      and L. (V.) guyanensis are circulating among wild and synanthropic mammals
      present in the Xakriaba Reserve, highlighting the epidemiological diversity of
      ATL in this region.

PMID- 21890160
TI  - Evaluation of the safety and tolerability of a short higher-dose primaquine
      regimen for presumptive anti-relapse therapy in healthy subjects.
AB  - The safety and tolerability of primaquine (PQ) administered as a short higher
      dose (30mg twice daily for 7 days) regimen in 203 Australian Defence Force
      personnel was evaluated in an open-label presumptive anti-relapse therapy study.
      No clinically significant differences were measured in the subjects'
      haematological and biochemical indices before and after PQ treatment. The most
      common adverse events were nausea, abdominal pain, headache and insomnia, many of
      which were mild in severity (30%; 60/203) and transient; 19% of subjects (39/203)
      experienced moderate (with some interference with daily duties requiring no or
      minimal medical therapy) adverse events. Two subjects (1%) had severe
      gastrointestinal adverse events requiring cessation of medication, but neither
      was seriously ill. Ten subjects (5%) had peripheral cyanosis (blueness of the
      lips), but none reported any respiratory compromise. These findings suggest that
      the short higher-dose PQ regimen is safe and well tolerated, which could improve
      PQ compliance and effectiveness.

PMID- 21890161
TI  - Massive enlargement of a paraumbilical vein in a patient with advanced portal
      hypertension.

PMID- 21890162
TI  - Solution to the influence of the MSSW propagating velocity on the bandwidths of
      the single-scale wavelet-transform processor using MSSW device.
AB  - The objective of this research was to investigate the possibility of solving the
      influence of the magnetostatic surface wave (MSSW) propagating velocity on the
      bandwidths of the single-scale wavelet transform processor using MSSW device. The
      motivation for this work was prompted by the processor that -3dB bandwidth varies
      as the propagating velocity of MSSW changes. In this paper, we present the
      influence of the magnetostatic surface wave (MSSW) propagating velocity on the
      bandwidths as the key problem of the single-scale wavelet transform processor
      using MSSW device. The solution to the problem is achieved in this study. we
      derived the function between the propagating velocity of MSSW and the -3dB
      bandwidth, so we know from the function that -3dB bandwidth of the single-scale
      wavelet transform processor using MSSW device varies as the propagating velocity
      of MSSW changes. Through adjusting the distance and orientation of the permanent
      magnet, we can implement the control of the MSSW propagating velocity, so that
      the influence of the MSSW propagating velocity on the bandwidths of the single
      scale wavelet transform processor using MSSW device is solved.

PMID- 21890163
TI  - Porcine circovirus genotype 2a (PCV2a) and genotype 2b (PCV2b) recombinant
      mutants showed significantly enhanced viral replication and altered antigenicity
      in vitro.
AB  - Two recombinant mutants of porcine circovirus type 2 (PCV2), which resulted from
      replacement of a genomic fragment containing the open reading frame 2 (ORF2) of
      genotype PCV2b with that of genotype PCV2a, were obtained initially from co
      infection with PCV2a and 2b genotype viruses in vitro. The two mutant viruses
      contained the ORF1 sequence from genotype PCV2b and the ORF2 sequence from
      genotype PCV2a. They were designated according to the nomenclature proposed by
      Grau et al., indicating the origin of the ORF1 sequence first and that of the
      ORF2 sequence second, i.e., PCV2b(JF11)/2a(CL1) and PCV2b(YJ)/2a(CL1). The
      replication efficiencies of the two PCV2 recombinant mutants were enhanced
      significantly and their antigenicities were altered significantly in vitro when
      compared with their parental strains.

PMID- 21890164
TI  - A chimeric measles virus with a lentiviral envelope replicates exclusively in
      CD4+/CCR5+ cells.
AB  - We generated a replicating chimeric measles virus in which the hemagglutinin and
      fusion surface glycoproteins were replaced with the gp160 envelope glycoprotein
      of simian immunodeficiency virus (SIVmac239). Based on a previously cloned live
      attenuated Schwarz vaccine strain of measles virus (MV), this chimera was rescued
      at high titers using reverse genetics in CD4+ target cells. Cytopathic effect
      consisted in the presence of large cell aggregates evolving to form syncytia, as
      observed during SIV infection. The morphology of the chimeric virus was identical
      to that of the parent MV particles. The presence of SIV gp160 as the only
      envelope protein on chimeric particles surface altered the cell tropism of the
      new virus from CD46+ to CD4+ cells. Used as an HIV candidate vaccine, this
      MV/SIVenv chimeric virus would mimic transient HIV-like infection, benefiting
      both from HIV-like tropism and the capacity of MV to replicate in dendritic
      cells, macrophages and lymphocytes.

PMID- 21890165
TI  - Operational aspects of the desulfurization process of energy gases mimics in
      biotrickling filters.
AB  - Biological removal of reduced sulfur compounds in energy-rich gases is an
      increasingly adopted alternative to conventional physicochemical processes,
      because of economical and environmental benefits. A lab-scale biotrickling filter
      reactor for the treatment of high-H(2)S-loaded gases was developed and previously
      proven to effectively treat H(2)S concentrations up to 12,000 ppm(v) at gas
      contact times between 167 and 180 s. In the present work, a detailed study on
      selected operational aspects affecting this system was carried out with the
      objective to optimize performance. The start-up phase was studied at an inlet
      H(2)S concentration of 1000 ppm(v) (loading of 28 g H(2)S m(-3) h(-1)) and
      inoculation with sludge from a municipal wastewater treatment plant. After
      reactor startup, the inlet H(2)S concentration was doubled and the influence of
      different key process parameters was tested. Results showed that there was a
      significant reduction of the removal efficiency at gas contact times below 120 s.
      Also, mass transfer was found to be the main factor limiting H(2)S elimination,
      whereas performance was not influenced by the bacterial colonization of the
      packed column after the initial startup. The effect of gas supply shutdowns for
      up to 5 days was shown to be irrelevant on process performance if the trickling
      liquid recirculation was kept on. Also, the trickling liquid velocity was
      investigated and found to influence sulfate production through a better use of
      the supplied dissolved oxygen. Finally, short-term pH changes revealed that the
      system was quite insensitive to a pH drop, but was markedly affected by a pH
      increase, affecting both the biological activity and the removal of H(2)S.
      Altogether, the results presented and discussed herein provide new insight and
      operational data on H(2)S removal from energy gases in biotrickling filters.

PMID- 21890166
TI  - Effect of short-chain organic acids on the enhanced desorption of phenanthrene by
      rhamnolipid biosurfactant in soil-water environment.
AB  - This study investigated the effect of short-chain organic acids on biosurfactant
      enhanced mobilization of phenanthrene in soil-water system. The desorption
      characteristics of phenanthrene by soils were assessed in the presence of
      rhamnolipid and four SCOAs, including acetic acid, oxalic acid, tartaric acid and
      citric acid. The tests with rhamnolipid and different organic acids could attain
      the higher desorption of phenanthrene compared to those with only rhamnolipid.
      Among the different combinations, the series with rhamnolipid and citric acid
      exhibited more significant effect on the desorption performance. The removal of
      phenanthrene using rhamnolipid and SCOAs gradually increased as the SCOA
      concentration increased up to a concentration of 300 mmol/L. The effects of pH,
      soil dissolved organic matter and ionic strength were further evaluated in the
      presence of both biosurfactant and SCOAs. The results showed that the extent of
      phenanthrene desorption was more significant at pH 6 and 9. Desorption of
      phenanthrene was relatively lower in the DOM-removed soils with the addition of
      biosurfactant and SCOAs. The presence of more salt ions made phenanthrene more
      persistent on the solid phase and adversely affected its desorption from
      contaminated soil. The results from this study may have important implications
      for soil washing technologies used to treat PAH-contaminated soil and
      groundwater.

PMID- 21890167
TI  - Dietary uptake of polybrominated diphenyl ethers (PBDEs), occurrence and
      profiles, in aquacultured turbots (Psetta maxima) from Galicia, Spain.
AB  - Polybromodiphenyl ethers (PBDEs) are one of the many toxic chemicals present in
      the environment and in the food we eat every day, being fish one of the main
      sources of persistent organic pollutants in our diet; like other lipid-related
      contaminants, they are of concern since they can bioaccumulate and biomagnify
      through the trophic chain. We published a study focused on the dietary uptake of
      dioxins and furans (PCDD/Fs) and dioxin-like polychlorobiphenyls (dl-PCBs) in a
      set of samples of Spanish farmed turbot (Blanco et al., 2007). In the present
      paper, we extend the study to PBDEs to provide more information about the uptake
      and transfer from feed to fish of halogenated contaminants. PBDEs in the feeds
      (2.35-4.76 ng g(-1)) were reflected in turbot fillets (0.54-2.05 ng g(-1)):
      predominant congeners were tetra-BDE 47, penta-BDEs 99 and 100. It is remarkable
      that tetra-BDE 49, accounting for only 2% in the feed, contributed to 15% of
      total PBDEs in turbot fillets. Dietary net accumulation values, 30-45%, showed
      that tri-, tetra-, penta- and hexa-BDEs were as efficiently transferred into
      turbot as dl-PCBs and tetra- and penta-chlorinated PCDD/Fs. Lipid-normalized
      biomagnification factors relating concentration in fish and in feed, BMFs>1 were
      obtained, except for BDE 209. BDE 49 accumulation, 90%, was possibly contributed
      by metabolism of higher brominated BDEs. Implication in aquaculture management is
      a need for uncontaminated fish feed to offer safe products.

PMID- 21890168
TI  - Influence of anionic, cationic and nonionic surfactants on adsorption and
      desorption of oxytetracycline by ultrasonically treated and non-treated
      multiwalled carbon nanotubes.
AB  - High adsorption capacity of carbon nanotubes (CNTs) may greatly determine the
      bioavailability and mobility of organic contaminants. The fate of contaminants
      adsorbed by CNTs may be substantially influenced by surfactants used both in the
      synthesis and dispersion of CNTs. The aim of this research was to determine the
      influence of surfactants (nonionic - TX100, cationic - CTAB and anionic - SDBS)
      on adsorption and desorption of oxytetracycline (OTC) by multiwalled carbon
      nanotubes (MWCNTs). The surfactants used had a substantial influence on both
      adsorption and desorption of OTC. The direction of changes depended clearly on
      the type of surfactant. In case of anionic SDBS, increased adsorption of OTC by
      MWCNTs was observed. The presence of TX100 and CTAB decreased the adsorption of
      OTC by MWCNTs significantly. The increase of OTC adsorption after ultrasonic
      treatment was observed in case of MWCNTs alone and MWCNTs with SDBS and TX100.
      However, ultrasonic treatment caused OTC adsorption decrease in the presence of
      CTAB. The change of pH had also an important effect on OTC adsorption in the
      presence of surfactants. Depending on the surfactant and pH, an increase or
      decrease of OTC adsorption was observed. The presence of surfactants increased
      OTC desorption from MWCNTs significantly as follows: SDBS=CTAB < TX100. The
      results obtained suggest new potential threats and constitute a basis for further
      research considering the bioavailability and toxicity of antibiotics in the
      presence of MWCNTs and surfactants.

PMID- 21890169
TI  - Contamination of nonylphenolic compounds in creek water, wastewater treatment
      plant effluents, and sediments from Lake Shihwa and vicinity, Korea: comparison
      with fecal pollution.
AB  - Nonylphenolic compounds (NPs), coprostanol (COP), and cholestanol, major
      contaminants in industrial and domestic wastewaters, were analyzed in creek
      water, wastewater treatment plant (WWTP) effluent, and sediment samples from
      artificial Lake Shihwa and its vicinity, one of the most industrialized regions
      in Korea. We also determined mass discharge of NPs and COP, a fecal sterol, into
      the lake, to understand the linkage between discharge and sediment contamination.
      Total NP (the sum of nonylphenol, and nonylphenol mono- and di-ethoxylates) were
      0.32-875 MUg L(-1) in creeks, 0.61-87.0 MUg L(-1) in WWTP effluents, and 29.3-230
      MUg g(-1) TOC in sediments. Concentrations of COP were 0.09-19.0 MUg L(-1) in
      creeks, 0.11-44.0 MUg L(-1) in WWTP effluents, and 2.51-438 MUg g(-1) TOC in
      sediments. The spatial distributions of NPs in creeks and sediments from the
      inshore region were different from those of COP, suggesting that Lake Shihwa
      contamination patterns from industrial effluents differ from those from domestic
      effluents. The mass discharge from the combined outfall of the WWTPs, located in
      the offshore region, was 2.27 kg d(-1) for NPs and 1.00 kg d(-1) for COP,
      accounting for 91% and 95% of the total discharge into Lake Shihwa, respectively.
      The highest concentrations of NPs and COP in sediments were found in samples at
      sites near the submarine outfall of the WWTPs, indicating that the submarine
      outfall is an important point source of wastewater pollution in Lake Shihwa.

PMID- 21890170
TI  - Monitoring of PBDEs concentration in umbilical cord blood and breast milk from
      Korean population and estimating the effects of various parameters on
      accumulation in humans.
AB  - In this study, we investigated concentration, congener distribution pattern, and
      effects of potential environmental factors that affect PBDE accumulation. We also
      estimated correlation between PBDE concentration and health status or thyroid
      function by analyzing 90 cord blood and 21 breast milk samples obtained from
      Korean population. Seven from tri- to hepta-BDEs were analyzed by solid phase
      extraction-high-resolution gas chromatography/high-resolution mass spectrometry
      (SPE-HRGC/HRMS). The total concentration of 7 PBDEs in cord blood was 2.786-94.64
      ng g(-1) lipid and that in breast milk was 1.076-8.664 ng g(-1) lipid. Tetra-BDE
      (#47) was the predominant type of PBDE and was present at concentrations of over
      40% in both sample types. A weak correlation was observed between the
      concentration of BDE28 and 153 and thyroid hormone concentration only in the
      breast milk samples. In children, a weak negative correlation was observed
      between free thyroxine (FT4) concentration and BDE28 concentration (0.302,
      p<0.05), while in mothers, a weak positive correlation was observed between
      thyroid hormone concentration and BDE153 concentration (0.403, p<0.05). No
      significant correlations between PBDE concentration and work and residential
      environments were found in this study, but a weak correlation between BDE
      concentration in cord blood and potential PBDE sources was confirmed by
      investigating the frequency of oil paint usage (0.510, p<0.001). A weak
      correlation was also found between PBDE concentration in breast milk during
      pregnancy and dietary habits such as green tea drinking (0.541, p=0.025) and
      Trichiuridae intake (0.565, p=0.015).

PMID- 21890171
TI  - Longitudinal increases in PCDD/F and dl-PCB concentrations in human milk in
      northern China.
AB  - There is a dearth of information on the temporal changes in polychlorinated
      dibenzodioxin/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (dl
      PCBs) contamination, in both environmental and biological specimens, in China. We
      compared the concentrations of PCDD/Fs and dl-PCBs in human milk collected in
      Shijiazhuang, Hebei Province, in northern China in 2002 (n=30) and 2007 (n=20).
      The level of PCDD/Fs and dl-PCBs showed an increasing trend. The mean
      concentrations of PCDD/Fs plus dl-PCBs were 4.47 TEQ pg g(-1) fat and 6.24 TEQ pg
      g(-1) fat in human milk from Shijiazhuang in 2002 and in 2007, respectively.
      Based on statistical analysis of questionnaire data collected by in-person
      interviews with mothers, we found positive correlations between consumption of
      sea fish and PCDFs. The PCDDs, PCDFs, PCDD/Fs, and PCDD/Fs plus dl-PCBs levels in
      individuals consuming greater amounts of sea fish were higher than those
      consuming less sea fish, both with and without adjustments for potential
      confounding factors. Among 17 congeners of PCDD/Fs, the 2,3,7,8-TCDF, 1,2,3,7,8
      PeCDF, 2,3,4,7,8-PeCDF, 1,2,3,4,7,8-HxCDF, 1,2,3,6,7,8-HxCDF, and 2,3,4,6,7,8
      HxCDF congener concentrations in 2007 increased 134%, 55%, 53%, 57%, 65% and 130%
      when compared to 2002 levels, respectively. The 2007 dl-PCB congener levels were
      greater than those of the 2002 samples, with the exception of PCB81 and PCB77.
      Specifically, PCB105, PCB114, PCB118, PCB123 and PCB156 had increased greater
      than twofold from 2002 to 2007. Continuous surveillance of PCDD/F and dl-PCB
      levels in human milk is needed to accurately evaluate both environmental
      contamination and the human health risk to neonates in China.

PMID- 21890172
TI  - Application of a computational model for Michael addition reactivity in the
      prediction of toxicity to Tetrahymena pyriformis.
AB  - A computational model to predict acute aquatic toxicity to the ciliate
      Tetrahymena pyriformis has been developed. A general prediction of toxicity can
      be based on three consecutive steps: 1. Identification of a potential reactive
      mechanism via structural alerts; 2. Confirmation and quantification of
      (bio)chemical reactivity; 3. Establishing a relationship between calculated
      reactivity and toxicity. The method described herein uses a combination of a
      reactive toxicity (RT) model, including computed kinetic rate constants for
      adduct formation (log k) via a Michael acceptor mechanism of action, and baseline
      toxicity (BT), modelled by hydrophobicity (octanol-water partition coefficient).
      The maximum of the RT and BT values defines acute toxicity for a particular
      compound. The reactive toxicity model is based on site-specific steric and
      quantum chemical ground state electronic properties. The performance of the model
      was examined in terms of predicting the toxicity of 106 potential Michael
      acceptor compounds covering several classes of compounds (aldehydes, ketones,
      esters, heterocycles). The advantages of the computational method are described.
      The method allows for a closer and more transparent mechanistic insight into the
      molecular initiating events of toxicological endpoints.

PMID- 21890173
TI  - The use of hard- and soft-modelling to predict radiostrontium solid-liquid
      distribution coefficients in soils.
AB  - The solid-liquid distribution coefficient (K(d)) is the parameter that governs
      the incorporation of contaminants in soils. Its estimation allows the prediction
      of the fate of contaminants in the short- and long-term after a contamination
      event. Here, the K(d) of radiostrontium (K(d)(Sr)), a radionuclide of significant
      environmental interest, was predicted by hard models, which are based on
      knowledge of the mechanisms governing its sorption, and by soft models based on
      Partial Least Squares (PLS), using a large data set with the main soil
      parameters. The two approaches were tested and compared for 30 soils in Spain.
      Correlations between the predicted and experimental values of K(d)(Sr) obtained
      using hard- and soft-modelling showed slopes close to 1 and regression
      coefficients higher than 0.95, which confirms that both approaches are able to
      obtain satisfactory estimates for K(d)(Sr) from soil parameters.

PMID- 21890174
TI  - Predicting the bioavailability of sediment-associated polybrominated diphenyl
      ethers using a 45-d sequential Tenax extraction.
AB  - A 45-d Tenax extraction was used to evaluate the bioavailability of
      polybrominated diphenyl ethers (PBDEs) in three spiked sediments. The effect of
      aging on desorption kinetics of PBDEs was investigated by incubating one of the
      sediments for 7, 14, 30 and 60 d at room temperature. Desorption kinetics were
      well described by a three-compartment model. The fraction of very slow desorption
      (Fvs) contributed the most of the desorbed PBDEs from sediments. The total
      desorption amount of PBDEs decreased with the increase of total organic carbon in
      the sediments, suggesting that organic matter is an important factor controlling
      the partition of PBDEs in sediments. The total desorption amount of PBDEs
      decreased while log [(Fslow+Fvs)/Frap] increased with logKow of PBDE congeners,
      indicating that the bioavailability of PBDEs in sediment decreases with logKow of
      the congeners. As the residential time of PBDEs in the sediment increased from 7
      to 60 d, Frap of individual PBDE congeners decreased gradually with simultaneous
      increase of Fvs. There was a good positive correlation between Frap and F6/F24,
      indicating that either 6 h or 24 h Tenax extraction could be a proxy for Frap and
      bioavailability. In general, the results in present study suggest that the
      bioavailability of nona- and deca-BDEs in sediment is very low due to their
      strong hydrophobicity and large molecular size.

PMID- 21890175
TI  - Multivariate toxicity profiles and QSAR modeling of non-dioxin-like PCBs--an
      investigation of in vitro screening data from ultra-pure congeners.
AB  - The non-dioxin-like PCBs (NDL-PCBs) found in food and human samples have a
      complex spectrum of adverse effects, but lack a detailed risk assessment. The
      toxicity profiles of 21 carefully selected PCBs (19 NDL-PCBs) were identified by
      in vitro screening in 17 different assays on specific endpoints related to
      neurotoxicity, endocrine disruption and tumor promotion. To ensure that the test
      results were not affected by polychlorinated dioxins, dibenzofurans or DL-PCB
      contaminants, the NDL-PCB congeners were thoroughly purified before testing.
      Principal component analysis (PCA) was used to derive general toxicity profiles
      from the in vitro screening data. The toxicity profiles indicated different
      structure-activity relationships (SAR) and distinct mechanisms of action. The
      analysis also indicated that the NDL-PCBs could be divided into two groups. The
      first group included generally smaller, ortho-substituted congeners, comprising
      PCB 28, 47, 51, 52, 53, 95, 100, 101, 104 and 136, with PCB 95, 101 and 136 as
      generally being most active. The second group comprising PCB 19, 74, 118, 122,
      128, 138, 153, 170, 180 and 190 had lower biological activity in many of the
      assays, except for three endocrine-related assays. The most abundant congeners,
      PCB 138, 153, 170, 180 and 190, cluster in the second group, and thereby show
      similar SAR. Two quantitative structure-activity relationship (QSAR) models could
      be developed that added information to the SAR and could aid in risk assessments
      of NDL-PCBs. The QSAR models predicted a number of congeners as active and among
      these e.g., PCB 18, 25, 45 and 49 have been found in food or human samples.

PMID- 21890176
TI  - PCBs in wild mussels (Mytilus galloprovincialis) from the N-NW Spanish coast:
      current levels and long-term trends during the period 1991-2009.
AB  - Concentrations of polychlorinated biphenyls (PCBs) were determined in wild
      mussels (Mytilus galloprovincialis) from seven areas of the N-NW Spanish coast,
      during the period 1991-2009. The studied area is comprised of highly productive
      ecosystems which support important commercial fishing and shellfishing
      activities. The seven PCBs indicator congeners recommended by ICES (IUPAC nos.
      28, 52, 101, 118, 138, 153 and 180), were analysed by gas chromatography with an
      electron capture detector (GC-ECD). Lowest average concentrations of PCBs were
      recorded in Arousa (1.04 MUg kg(-1) wet weight), a low populated area with no
      industry; while the highest levels were found in areas near cities and/or showing
      a high industrial activity such as: Bilbao Zierbena (139 MUg kg(-1) ww) or A
      Coruna (55 MUg kg(-1) ww). The hexachlorinated congeners CB153 and CB138
      dominated the profiles in all wild mussel populations, although a geographical
      pattern was found in which the relative contributions of the lower chlorinated
      congeners were higher in the west coast (Rias of Vigo, Pontevedra and Arousa),
      which may reflect the occurrence of recent inputs of those compounds in the area.
      Finally, the application of the Mann-Kendall's test demonstrate the existence of
      a significant decrease in PCBs levels since 1991 up to 1996 in the studied area,
      whereas either a slow decrease or stable concentrations were registered over the
      past decade.

PMID- 21890177
TI  - Mousterian technology and settlement dynamics in the site of Hummal (Syria).
AB  - The site of Hummal is one of several artesian springs in the El Kowm area
      (Central Syria) that became the focus of archaeological research at the beginning
      of the 1980s. The archaeological sequence spans the whole Paleolithic period and
      the spring is therefore a reference site for the Paleolithic in the interior part
      of the Levant. Archaeological remains are found in a more than 15 m thick
      succession of deposits that contain Lower, Middle and Upper Paleolithic
      assemblages. The present paper addresses archaeological and geological data,
      which were recovered during recent years' excavations of Mousterian deposits.
      With a compiled stratigraphy of over 6 m and more than 30 archaeological levels,
      the Hummal Mousterian sequence is especially apt for the reconstruction of
      changing site-use patterns through time. Lithic analysis helps to elucidate
      technological traditions as well as organization and the changing ways in which
      mobile foragers used a site in the context of an arid steppe. Results contribute
      further to existing models of Levantine Middle Paleolithic land-use strategies
      and demography in the time span of between 130,000 and 50,000 BP, and partly
      contradict existing interpretations. Two different lithic industries were
      defined, which correspond to a C- and B-type Levantine Mousterian according to
      the three-stage Tabun model. The discovery of a C-type Mousterian in the lower
      deposits further extends the geographical range of this cultural facies into the
      interior arid part of the Levant. An increasing importance and standardization of
      Levallois points is observable and thereby supports models that postulate a
      growing specialization of hunting techniques at the end of the Middle
      Paleolithic.

PMID- 21890178
TI  - Macrophage migration inhibitory factor induces ICAM-1and thrombomobulin
      expression in vitro.
AB  - Macrophage migration inhibitory factor (MIF) is an important cytokine in the
      modulation of inflammatory and immune responses, but its role in coagulation
      remains to be elucidated. In this study, we investigated the potential role of
      MIF in coagulation through its influence on two factors, thrombomodulin (TM) and
      intercellular adhesion molecule-1 (ICAM-1). Recombinant human MIF was added to
      human microvascular endothelial cell line (HMEC-1) to investigate its influence
      on the expression of TM and ICAM-1. The results showed that both TM and ICAM-1
      were induced with MIF addition in a dose-dependent and time-dependent manner. The
      expression of ICAM-1 and TM was increased as MIF doses were increased, with the
      highest expression seen at 12 hr after 400 ng/ml of MIF treatment. Besides, anti
      MIF antibody treatment reduced the TM expression in HMEC-1 cells. In conclusion,
      our data support a role of MIF as an important factor in the regulation of
      coagulation.

PMID- 21890179
TI  - Immunolocalization of Smad4 protein in the testis of domestic fowl (Gallus
      domesticus) during postnatal development.
AB  - The transforming growth factor beta (TGF-beta) superfamily exerts a wide range of
      effects on biological events, including spermatogenesis. Smad proteins are
      downstream signal mediators, which transduce TGF-beta signals from the cell
      surface to the nucleus. Smad4 protein is the common transducer of the TGF-beta
      superfamily that participates in the signaling of all the members of TGF-beta
      superfamily. Smad4 is expressed in the mammalian testis and is believed to play
      an important role during testicular development and spermatogenesis. Information
      about Smad4 distribution and function in the testis of birds, including the
      domestic fowl, is still unclear. In the current study, our objective was to
      clarify the signal transduction pathway of the TGF-beta superfamily in the
      regulation of testicular development and spermatogenesis by investigating the
      expression of Smad4 protein in the testis of newborn, prepuberty, puberty and
      adult domestic fowl. Cellular localization of Smad4 was determined by
      immunohistochemistry. Our study revealed that the Smad4 was widely expressed in
      the fowl testis, mainly immunolocalized in the cytoplasm of Sertoli cells, Leydig
      cells and germ cells. The presence of Smad4 protein in these testicular cells
      provides molecular and morphological evidence for TGF-beta signal transduction
      during testicular development and spermatogenesis.

PMID- 21890180
TI  - A modified ureteroileal anastomosis technique for Bricker urinary diversion.
AB  - OBJECTIVE: Up to 10% of patients who have undergone the Bricker ileal conduit
      urinary diversion may develop ureteroileal anastomotic complications that are
      more frequently associated with the left side ureter. We have therefore modified
      the standard Bricker ileal conduit technique to minimize the anastomotic
      complications associated with the left side ureter. MATERIALS AND METHODS: In our
      modification, the proximate end of the ileal conduit was brought from the right
      side to the left under the mesosigmoid in an isoperistaltic fashion. The left
      ureter that remained in the natural extraperitoneal location was anastomosed to
      the ileal segment in the usual end-to-side fashion without the need of extensive
      ureteral dissection. RESULTS: A series of 42 patients have undergone ileal
      conduit urinary diversion using this modified technique. During a median follow
      up period of 18.6 months, this technique was found to have no associated major
      perioperative complications and early- and intermediate-term ureteroileal
      anastomotic complications from both sides of the ureters. CONCLUSION: Our
      modified ileal conduit diversion technique was easy and safe to perform, and may
      serve as an alternative technique for the standard Bricker ileal conduit urinary
      diversion, especially when the left distal ureter was involved extensively with
      urothelial carcinoma.

PMID- 21890181
TI  - Pure NOTES transvesical venous ligation: translational animal model of
      varicocelectomy.
AB  - OBJECTIVE: To assess the feasibility of pure natural orifice transluminal
      endoscopic surgery (NOTES) transvesical venous ligation mimicking bilateral
      varicocelectomy in an animal model. MATERIALS AND METHODS: Transvesical NOTES
      bilateral venous ligation was performed in 6 female pigs by considering lower
      epigastric vessels as a model for gonadal vessels. Under flexible cystoscopic
      guidance, a cystotomy was created on the anterior bladder. The flexible
      cystoscope was introduced through the over tube, and the lower epigastric vessels
      were visualized in retroflexion. Thulium laser was used to cut and coagulate the
      vessels. A bladder catheter was left in place for 4 days in all animals and they
      were sacrificed 15 days after the procedure. RESULTS: The procedure was
      successfully carried out in all animals without intraoperative complications.
      Epigastric vessels were safely cut and coagulated using the thulium laser. Median
      time for the overall procedure, including establishment of the transvesical port,
      was 23 minutes (range 20-30). No complications were encountered during the
      postoperative follow-up period. Postmortem examination revealed complete
      coagulation and separation of vessels. CONCLUSION: An animal model mimicking a
      NOTES transvesical bilateral varicocelectomy procedure is successfully shown in
      the present study. Despite being encouraging, these novel findings need to be
      interpreted with caution. Further research is warranted and development of
      purpose-built instrumentation is awaited to define potential urological
      applications of transvesical NOTES.

PMID- 21890182
TI  - Oncological and functional outcomes after robot-assisted radical cystectomy:
      critical review of current status.
AB  - Although open radical cystectomy (ORC) remains the gold-standard management of
      muscle-invasive bladder cancer, the number of centers performing robotic-assisted
      radical cystectomy (RARC) has recently increased, prompting greater oncological
      outcome concerns. Although limited in patient number and follow-up, short-term
      RARC data from centers of excellence appear to show the approach to be safe and
      effective, with improved perioperative and functional outcomes, while maintaining
      comparable oncologic efficiency. Nevertheless, despite the surge of centers
      adopting RARC, the long-term effectiveness of minimally-invasive techniques has
      yet to be proven. This review of published RARC series affirms the need for
      prospective, long-term, controlled studies to adequately evaluate the role of
      robotics in bladder cancer surgery.

PMID- 21890183
TI  - Transurethral resection of the prostate with monopolar resectoscope: single
      surgeon experience and long-term results of after 3589 procedures.
AB  - OBJECTIVE: To present our clinical outcomes and to assess the impact of
      technological improvements that have occurred recently in transurethral resection
      of the prostate (TURP) on its morbidity. METHODS: The data from the 3589 patients
      who underwent conventional monopolar TURP for BPH from March 2000 to December
      2008 were evaluated retrospectively. Data were analyzed to obtain perioperative
      and postoperative complications, operative time, weight of prostate chips
      resected, time to catheter removal, and hospitalization time. Patients were
      followed at 3 months and then yearly. The follow-up included the International
      Prostate Symptom Score (IPSS), quality of life score (QoL), maximum urinary flow
      rate (Q(max.)), and prostate-specific antigen. The significant improvements in
      mean the IPSS, QoL score, and Q(max.) were observed in postoperative visits.
      RESULTS: Intraoperative perforation of prostatic capsule or bladder neck was
      observed in 27 (0.75%) patients. In the early postoperative period, clot
      retention with secondary bleeding was observed in 81 (2.3%) patients.
      Recatheterization was required in 195 (5.4%) patients. Mild to moderate dysuria
      was observed in 819 (23%) patients. Urinary tract infection occurred in 234
      (6.5%) cases. Severe dysuria, urgency, and urge incontinence was observed in 93
      (2.6%) patients in the first week after surgery. During the follow-up period,
      urethral stricture and bladder neck contracture occurred in 117 (3.2%) and 39
      (1.08%) patients, respectively. There was no the iatrogenic incontinence. Re
      operation as a result of rest prostatic adenoma was required in 158 (4.4%)
      patients. CONCLUSION: These data demonstrate that a technical improvement in TURP
      provides a lower complication rate. Conventional monopolar TURP can now be
      performed with excellent long-term efficacy combined with reduced complications.

PMID- 21890184
TI  - Chronic rhinosinusitis: epidemiology and medical management.
AB  - Chronic rhinosinusitis (CRS) affects 12.5% of the US population. On epidemiologic
      grounds, some association has been found between CRS prevalence and air
      pollution, active cigarette smoking, secondhand smoke exposure, perennial
      allergic rhinitis, and gastroesophageal reflux. The majority of pediatric and
      adult patients with CRS are immune competent. Data on genetic associations with
      CRS are still sparse. Current consensus definitions subclassify CRS into CRS
      without nasal polyposis (CRSsNP), CRS with nasal polyposis (CRSwNP), and allergic
      fungal rhinosinusitis (AFRS). Evaluation and medical management of CRS has been
      the subject of several recent consensus reports. The highest level of evidence
      for treatment for CRSsNP exists for saline lavage, intranasal steroids, and long
      term macrolide antibiotics. The highest level of evidence for treatment of CRSwNP
      exists for intranasal steroids, systemic glucocorticoids, and topical steroid
      irrigations. Aspirin desensitization is beneficial for patients with aspirin
      intolerant CRSwNP. Sinus surgery followed by use of systemic steroids is
      recommended for AFRS. Other modalities of treatment, such as antibiotics for
      patients with purulent infection and antifungal drugs for patients with AFRS, are
      potentially useful despite a lack of evidence from controlled treatment trials.
      The various modalities of medical treatment are reviewed in the context of recent
      consensus documents and the author's personal experience.

PMID- 21890185
TI  - Low prevalence of IgE to cross-reactive carbohydrate determinants in beekeepers.

PMID- 21890186
TI  - In vitro maturation of canine oocytes co-cultured with bovine and canine
      granulosa cell monolayers.
AB  - The present study investigated the effects of bovine granulosa cell monolayers
      (BGML) and canine granulosa cell monolayers (CGML) on nuclear maturation of
      canine oocytes with and without cumulus cells. Cumulus-oocyte complexes (COCs) or
      cumulus-free oocytes were cultured in Dulbecco's Modified Eagle's Medium (DMEM,
      control group), DMEM with BGML (BGML group), or DMEM with CGML (CGML group) for
      72 h at 38.5  degrees C in 5% CO(2), 5% O(2,) and 90% N(2). All media were
      supplemented with 10% of FCS, 50 ng/mL of EGF, 2 MUg/mL of estradiol-17beta, 0.1
      IU/mL of hCG, 0.1 IU/mL of FSH, 0.25 mM of pyruvic acid, 100 MUM of beta
      mercaptoethanol, 100 IU/mL of penicillin, and 100 MUg/mL of streptomycin. In
      cumulus-enclosed oocytes retrieved from ovaries at estrus and/or diestrus, the
      highest percentage of M-II oocytes (P < 0.05) was present in the BGML group
      (27.0%) compared with the CGML group (7.9%) and the control group (3.5%). In
      cumulus-free oocytes collected from ovaries at estrus and/or diestrus, the
      proportions of M-II oocytes co-cultured with the CGML were low (3.0%) and similar
      (P > 0.05) to proportions achieved with control (3.0%). However, the presence of
      BGML improved (P < 0.05) the ability of denuded oocytes to develop into M-II
      (10.2%). The BGML group had the highest overall meiotic resumption (P < 0.05),
      and least oocyte degeneration (P < 0.05) among experimental groups. In
      conclusion, BGML had a positive impact on the in vitro maturation system, as well
      as meiotic resumption of canine oocytes.

PMID- 21890187
TI  - Reproductive tract defense and disease in postpartum dairy cows.
AB  - This paper briefly reviews recent data and concepts on the development and
      mitigation of infection and inflammation in the reproductive tract of dairy cows
      during the first 2 mo after calving. The incidence of metritis is typically
      between 10 and 20%, of clinical endometritis or purulent vaginal discharge (PVD)
      approximately 15%, and of subclinical or cytological endometritis a further 15%.
      Worse postpartum negative energy balance is associated with more severe or
      prolonged uterine inflammation. Changes in feed intake, expression of genes for
      pro-inflammatory cytokines, notably interleukin (IL) 1, IL6 and IL8, circulating
      concentrations of beta-hydroxybutyrate (BHBA) or nonesterified fatty acids
      (NEFA), and innate immune function precede both metritis and endometritis by
      several weeks. Infections with Escherichia coli and Arcanobacterium pyogenes are
      associated with both metritis and PVD. There are new data to suggest that
      specific virulence factors in E. coli associated with adherence may be important
      in metritis and PVD. Cytological endometritis and PVD are overlapping but largely
      distinct conditions, and there are emerging data that cervicitis exists both
      concurrent with and separate from endometritis. Much remains to be learned about
      what initiates and sustains harmful inflammation of the reproductive tract. Such
      information is necessary to develop effective treatments for the various forms of
      disease and, more importantly, to develop means to prevent endometritis and
      cervicitis. In particular, vaccination against specific uterine pathogens and
      interventions to modulate innate immune response appear to be important avenues
      for investigation. Presently, commonly recommended best management practices for
      cows in the transition period are likely to be helpful to mitigate the risk of
      reproductive disease.

PMID- 21890188
TI  - Experimentally induced mastitis and metritis modulate soy bean derived isoflavone
      biotransformation in diary cows.
AB  - The present study compared the changes in isoflavone (daidzein and genistein) and
      their metabolite (equol and para-ethyl-phenol) concentrations in the blood plasma
      of cows with induced mastitis and metritis after feeding with soy bean. Sixteen
      cows were divided into four groups: control for mastitis group, cows with induced
      mastitis group, control for metritis group, and cows with induced metritis group.
      All cows were fed a single dose of 2.5 kg of soy bean and then blood samples were
      taken from the jugular vein for 8 h at predetermined intervals. The
      concentrations of soy bean-derived isoflavones and their active metabolites were
      measured in the blood plasma on HPLC system. beta-Glucuronidase activity in the
      blood plasma of cows was measured by fluorometric method. In the blood plasma of
      cows with induced mastitis and metritis, we found considerably higher
      concentrations and time-dependent increase in isoflavone metabolites (equol and
      para-ethyl-phenol) with reference to cyclic cows (P < 0.05). Moreover, we noticed
      significant decrease of genistein in the blood plasma of the cows with induced
      metritis compared with control cows (P < 0.05). In addition, in the blood plasma
      of the cows with induced metritis, we found an increase in beta-glucuronidase
      activity compared with control cows (P < 0.05). In conclusion, health status of
      the females influenced the concentrations of isoflavone metabolites in the blood
      plasma of the cows. Experimentally induced mastitis and metritis increased
      isoflavone absorption, biotransformation and metabolism. Therefore, we suggest
      that cows with induced mastitis and metritis are more exposed to active
      isoflavone metabolite actions than healthy cows.

PMID- 21890189
TI  - Improving post-transfer survival of bovine embryos produced in vitro: actions of
      insulin-like growth factor-1, colony stimulating factor-2 and hyaluronan.
AB  - Technologies for in vitro embryo production have the potential to enhance the
      efficiency of cattle production systems. However, utilization of in vitro
      produced embryos for transfer remains limited throughout much of the world.
      Despite improvements over the past two decades, problems associated with the
      production of bovine embryos in vitro still exist which limit the widespread
      commercial application of this technology. In particular, bovine embryos produced
      in vitro have a reduced capacity to establish and maintain pregnancy as compared
      with their in vivo-derived counterparts. Embryo competence for survival following
      transfer is improved by in vivo culture in the sheep oviduct, thus indicating
      that standard embryo culture conditions are sub-optimal. Therefore, one strategy
      to improve post-transfer survival is to modify embryo culture media to more
      closely mimic the in vivo microenvironment. The maternal environment in which the
      bovine embryo develops in vivo contains various growth factors, cytokines,
      hormones, and other regulatory molecules. In addition to affecting bovine embryo
      development in vitro, recent research indicates that embryo competence for
      survival following transfer can also be improved when such molecules are added to
      embryo culture medium. Among the specific molecules that can increase post
      transfer embryo survival are insulin-like growth factor-1 (IGF-1), colony
      stimulating factor-2 (CSF-2) and hyaluronan. This paper will review the effects
      IGF-1, CSF-2 and hyaluronan on post-culture embryo viability and discuss the
      potential mechanisms through which each of these molecules improves post-transfer
      survival.

PMID- 21890190
TI  - Estrus synchronization affects WNT signaling in the porcine reproductive tract
      and embryos.
AB  - The purpose of the study was to investigate an effect of estrus synchronization
      with prostaglandin (PG) F(2alpha) and PMSG/hCG on WNT4, WNT5A, WNT7A, beta
      catenin (CTNNB1) and E-cadherin (CDH1) gene expression. The weight of the uterus,
      morphometrical parameters of the endometrium and the number of CL were recorded.
      The analysis of estradiol (E(2)), prostaglandin (PG) F(2alpha) and E(2) content
      in the uterine luminal flushings (ULFs) and progesterone (P(4)) level in the
      blood serum were conducted. RNA was isolated from endometrial, luteal and
      embryonic tissue of pregnant non-synchronized (Control; n = 15) and pregnant
      synchronized (PGF(2alpha)/PMSG/hCG; n = 15) pigs. Whereas there was no change in
      uterine weight, differences in height of endometrial surface and glandular
      epithelium were found. However, height of the endometrium, number of the glands
      and capillaries were unaffected. The total number of the CLs was higher (P <
      0.05) in animals treated with PGF(2alpha)/PMSG/hCG. The amount of E(2) and P(4)
      was lower (P < 0.05, P < 0.001, respectively) in pregnant gilts administrated
      with PGF(2alpha)/PMSG/hCG. The concentration of PGF(2alpha) in ULFs was not
      affected by hormonal management, while PGE(2) was higher (P < 0.01) in hormonally
      in comparison to non-hormonally treated pigs. The content of WNT4 mRNA in
      conceptuses increased on particular Days studied in Control and
      PGF(2alpha)/PMSG/hCG administered animals. WNT7A and CTNNB1 were affected by
      PGF(2alpha)/PMSG/hCG treatment in both conceptuses (P < 0.001, P < 0.05) and
      endometrial tissue (P < 0.001, P < 0.01). The PGF(2alpha)/PMSG/hCG treatment
      resulted in elevated expression of WNT4 (P < 0.001) and CTNNB1 (P < 0.05) in
      luteal tissue in comparison to the Control gilts. Moreover, luteal amount of
      WNT5A mRNA was higher in PGF(2alpha)/PMSG/hCG animals in comparison to the
      Control group (P < 0.05). Presented data show that exogenous hormones
      administration can affect gene expression in the porcine reproductive tract and
      embryo.

PMID- 21890191
TI  - Immunoadsorption for haemolytic uraemic syndrome.

PMID- 21890192
TI  - Treatment of severe neurological deficits with IgG depletion through
      immunoadsorption in patients with Escherichia coli O104:H4-associated haemolytic
      uraemic syndrome: a prospective trial.
AB  - BACKGROUND: In May 2011, an outbreak of Shiga toxin-producing enterohaemorrhagic
      E coli O104:H4 in northern Germany led to a high proportion of patients
      developing post-enteritis haemolytic uraemic syndrome and thrombotic
      microangiopathy that were unresponsive to therapeutic plasma exchange or
      complement-blocking antibody (eculizumab). Some patients needed ventilatory
      support due to severe neurological complications, which arose 1 week after onset
      of enteritis, suggesting an antibody-mediated mechanism. Therefore, we aimed to
      assess immunoadsorption as rescue therapy. METHODS: In our prospective non
      controlled trial, we enrolled patients with severe neurological symptoms and
      confirmed recent E coli O104:H4 infection without other acute bacterial infection
      or raised procalcitonin concentrations. We did IgG immunoadsorption processing of
      12 L plasma volumes on 2 consecutive days, followed by IgG replacement (0.5 g/kg
      intravenous IgG). We calculated a composite neurological symptom score (lowest
      score was best) every day and assessed changes before and after immunoadsorption.
      FINDINGS: We enrolled 12 patients who initially presented with enteritis and
      subsequent renal failure; 10 (83%) of 12 patients needed renal replacement
      therapy by a median of 8.0 days (range 5-12). Neurological complications
      (delirium, stimulus sensitive myoclonus, aphasia, and epileptic seizures in 50%
      of patients) occurred at a median of 8.0 days (range 5-15) and mandated
      mechanical ventilation in nine patients. Composite neurological symptom scores
      increased in the 3 days before immunoadsorption to 3.0 (SD 1.1, p=0.038), and
      improved to 1.0 (1.2, p=0.0006) 3 days after immunoadsorption. In non-intubated
      patients, improvement was apparent during immunoadsorption (eg, disappearance of
      aphasia). Five patients who were intubated were weaned within 48 h, two within 4
      days, and two patients needed continued ventilation for respiratory problems. All
      12 patients survived and ten had complete neurological and renal function
      recovery. INTERPRETATION: Antibodies are probably involved in the pathogenesis of
      severe neurological symptoms in patients with E coli O104:H4-induced haemolytic
      uraemic syndrome. Immunoadsorption can safely be used to rapidly ameliorate these
      severe neurological complications. FUNDING: Greifswald University and Hannover
      Medical School.

PMID- 21890193
TI  - Human cardiosphere-seeded gelatin and collagen scaffolds as cardiogenic
      engineered bioconstructs.
AB  - Cardiac tissue engineering (CTE) aims at regenerating damaged myocardium by
      combining cells to a biocompatible and/or bioactive matrix. Collagen and gelatin
      are among the most suitable materials used today for CTE approaches. In this
      study we compared the structural and biological features of collagen (C-RGD) or
      gelatin (G-FOAM)-based bioconstructs, seeded with human adult cardiac progenitor
      cells in the form of cardiospheres (CSps). The different morphology between C-RGD
      (fibrous ball-of-thread-like) and G-FOAM (trabecular sponge-like) was evidenced
      by SEM analysis and X-ray micro-tomography, and was reflected by their different
      mechanical characteristics. Seeded cells were viable and proliferating after 1
      week in culture, and a reduced expression of cell-stress markers versus standard
      CSp culture was detected by realtime PCR. Cell engraftment inside the scaffolds
      was assessed by SEM microscopy and histology, evidencing more relevant cell
      migration and production of extracellular matrix in C-RGD versus G-FOAM.
      Immunofluorescence and realtime PCR analysis showed down-regulation of vascular
      and stemness markers, while early-to-late cardiac markers were consistently and
      significantly upregulated in G-FOAM and C-RGD compared to standard CSps culture,
      suggesting selective commitment towards cardiomyocytes. Overall our results
      suggest that CSp-bioconstructs have suitable mechanical properties and improved
      survival and cardiogenic properties, representing promising tools for CTE.

PMID- 21890194
TI  - Hemocompatibility of siRNA loaded dextran nanogels.
AB  - Although the behavior of nanoscopic delivery systems in blood is an important
      parameter when contemplating their intravenous injection, this aspect is often
      poorly investigated when advancing from in vitro to in vivo experiments. In this
      paper, the behavior of siRNA loaded dextran nanogels in human plasma and blood is
      examined using fluorescence fluctuation spectroscopy, platelet aggregometry, flow
      cytometry and single particle tracking. Our results show that, in contrast to
      their negatively charged counterparts, positively charged siRNA loaded dextran
      nanogels cause platelet aggregation and show increased binding to human blood
      cells. Although PEGylating the nanogels did not have a significant effect on
      their interaction with blood cells, single particle tracking revealed that it is
      necessary to prevent their aggregation in human plasma. We therefore conclude
      that PEGylated negatively charged dextran nanogels are the most suited for
      further in vivo studies as they do not aggregate in human plasma and exhibit
      minimal interactions with blood cells.

PMID- 21890195
TI  - Delivery of Oct4 and SirT1 with cationic polyurethanes-short branch PEI to aged
      retinal pigment epithelium.
AB  - Cationic polyurethane, a biodegradable non-viral vector, protects DNA from
      nuclease degradation and helps to deliver genes efficiently. Oct4, a POU-domain
      transcription factor, is highly expressed in maintaining pluripotency and
      cellular reprogramming process in stem cells. SirT1, a NAD-dependent histone
      deacetylase, is an essential mediator of cellular longevity. Herein we
      demonstrated that both Oct4 and SirT1 (Oct4/SirT1) expression was decreased in an
      age-dependent manner in retina with aged-related macular degeneration and retinal
      pigment epithelium cells (RPEs). To investigate the possible rescuing role of
      Oct4/SirT1, polyurethane-short branch polyethylenimine (PU-PEI) was used to
      deliver Oct4/SirT1 into aged RPEs (aRPEs) or light-injured rat retinas.
      Oct4/SirT1 overexpression increased the expression of several progenitor-related
      genes and the self-renewal ability of aRPEs. Moreover, Oct4/SirT1 overexpression
      resulted in the demethylation of the Oct4 promoter and enhanced the expression of
      antioxidant enzymes, which was accompanied by a decrease in intracellular ROS
      production and hydrogen peroxide-induced oxidative stress. Importantly, PU-PEI
      mediated Oct4/SirT1 gene transfer rescued retinal cell loss and improved
      electroretinographic responses in light-injured rat retinas. In summary, these
      data suggest that PU-PEI-mediated delivery of Oct4/SirT1 reprograms aRPEs into a
      more primitive state and results in cytoprotection by regulating the
      antioxidative capabilities of these cells.

PMID- 21890196
TI  - MicroRNAs in the regulation of interfacial behaviors of MSCs cultured on
      microgrooved surface pattern.
AB  - Cell-substrate interaction is one of the most important aspects of tissue
      engineering. Changes of MSCs interfacial behaviors were found to be triggered by
      10 MUm wide grooved pattern on poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)
      (PHBHHx). Global marker genes expression and miRNAs profiling analysis provided
      insights into the regulation network of the topography induced MSCs' cell
      responses including adhesion, proliferation, differentiation and apoptosis.
      Compared to MSCs cultured on the smooth substrates, MSCs incubated on
      microgrooved PHBHHx substrates showed increased expression of osteogenesis
      related marker genes including cbfa1, col1a1 and bmp2, and decreased expression
      of vcl, vinculin encoding gene, adipogenesis-related genes including lpl, des and
      acta2, as well as myogenesis-related genes of myh11 and nse. The miRNA
      microarrays revealed that 18 differentially-expressed miRNAs on microgrooved
      pattern had multiple target genes, contributing comprehensively to the cellular
      regulation process. Similar to the topography-triggered ostegenenesis, co
      transfection of the osteogenic miRNAs combination (miR-140, miR-214, miR-320, miR
      351 and miR-674-5p) was able to stimulate the expression of osteogenic marker
      genes. This study elucidated the important roles of miRNAs in the regulation
      processes of the microenvironment triggered cell behaviors, and provided clues
      for the PHA biomedical materials development.

PMID- 21890197
TI  - The determination of stem cell fate by 3D scaffold structures through the control
      of cell shape.
AB  - Stem cell response to a library of scaffolds with varied 3D structures was
      investigated. Microarray screening revealed that each type of scaffold structure
      induced a unique gene expression signature in primary human bone marrow stromal
      cells (hBMSCs). Hierarchical cluster analysis showed that treatments sorted by
      scaffold structure and not by polymer chemistry suggesting that scaffold
      structure was more influential than scaffold composition. Further, the effects of
      scaffold structure on hBMSC function were mediated by cell shape. Of all the
      scaffolds tested, only scaffolds with a nanofibrous morphology were able to drive
      the hBMSCs down an osteogenic lineage in the absence of osteogenic supplements.
      Nanofiber scaffolds forced the hBMSCs to assume an elongated, highly branched
      morphology. This same morphology was seen in osteogenic controls where hBMSCs
      were cultured on flat polymer films in the presence of osteogenic supplements
      (OS). In contrast, hBMSCs cultured on flat polymer films in the absence of OS
      assumed a more rounded and less-branched morphology. These results indicate that
      cells are more sensitive to scaffold structure than previously appreciated and
      suggest that scaffold efficacy can be optimized by tailoring the scaffold
      structure to force cells into morphologies that direct them to differentiate down
      the desired lineage.

PMID- 21890198
TI  - Non-viral gene transfection in vitro using endosomal pH-sensitive reversibly
      hydrophobilized polyethylenimine.
AB  - Reversibly hydrophobilized 10 kDa polyethylenimine (PEI) based on rapidly acid
      degradable acetal-containing hydrophobe was designed for nontoxic and highly
      efficient non-viral gene transfer. Water soluble PEI derivatives with average 5,
      9 and 14 units of pH-sensitive 2,4,6-trimethoxybenzylidene
      tris(hydroxymethyl)ethane (TMB-THME) hydrophobe per molecule, denoted as PEI-g
      (TMB-THME)(n), were readily obtained by treating 10 kDa PEI with varying amounts
      of TMB-THME-nitrophenyl chloroformate. Gel retardation assays showed that all PEI
      g-(TMB-THME)(n) derivatives could effectively condense DNA at an N/P ratio of
      5/1. Notably, polyplexes of PEI-g-(TMB-THME)(n) derivatives had smaller sizes
      (about 100~170 nm) and higher surface charges (+25 ~ +43 mV) than the parent 10
      kDa PEI at the same N/P ratios ranging from 10/1 to 40/1. MTT assays revealed
      that these PEI-g-(TMB-THME)(n) derivatives were practically non-toxic at polymer
      concentrations used in transfection experiments. The acetal degradation of PEI-g
      (TMB-THME)(9) was shown to be highly pH dependent in which half lives of 1.3, 2.8
      and 11 h were determined for pH 4.0, 5.0 and 6.0, respectively, while negligible
      hydrolysis (<12%) was observed after 24 h at pH 7.4. Gel electrophoresis, dynamic
      light scattering (DLS) and zeta potential analyses indicated that polyplexes
      formed at an N/P ratio of 10/1 were dissociated following 5 h incubation at pH
      5.0, highlighting the importance of hydrophobic TMB-THME moieties in DNA
      condensation and supporting that acetal hydrolysis in endosomes would facilitate
      DNA release. Notably, in vitro transfection experiments performed at N/P ratios
      of 10/1 and 20/1 in HeLa, 293T, HepG2 and KB cells using plasmid pGL3 expressing
      luciferase as the reporter gene showed that reversibly hydrophobilized PEIs had
      superior transfection activity to 25 kDa PEI control. For example, polyplexes of
      PEI-g-(TMB-THME)(14) showed about 235-fold and 175-fold higher transfection
      efficiency as compared to 10 kDa PEI in HeLa cells in serum-free and 10% serum
      media, respectively, which were approximately 7-fold and 16-fold higher than 25
      kDa PEI formulation at its optimal N/P ratio under otherwise the same conditions.
      Confocal laser scanning microscope (CLSM) studies confirmed that PEI-g-(TMB
      THME)(14) efficiently delivered Cy5-labeled DNA to the nuclei of HeLa cells.
      These endosomal pH-sensitive reversibly hydrophobilized PEIs have great
      potentials for safe and efficient non-viral gene transfection.

PMID- 21890199
TI  - Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation, lacking
      cutaneous involvement: Case series and literature review.
AB  - The diagnosis of blastic plasmacytoid dendritic cell neoplasm (BPDCN) can be
      challenging, owing to the absence of traditional lineage-specific markers, but is
      facilitated by CD4/CD56 co-expression and frequent skin involvement. Herein, we
      present our collective experiences with three BPDCN cases lacking cutaneous
      presentation and the inherent diagnostic pitfalls. Taken in context of similar
      historical cases, we suggest that BPDCN with "leukemic" presentation (L-BPDCN)
      otherwise presents no major distinguishing features and is at least as aggressive
      as its cutaneous-involved BPDCN counterpart.

PMID- 21890200
TI  - JAK2 46/1 haplotype predisposes to splanchnic vein thrombosis-associated BCR-ABL
      negative classic myeloproliferative neoplasms.

PMID- 21890201
TI  - Reversible pulmonary arterial hypertension likely related to long-term, low-dose
      dasatinib treatment for chronic myeloid leukaemia.

PMID- 21890202
TI  - Looking for suitable biomarkers in benthic macroinvertebrates inhabiting coastal
      areas with low metal contamination: comparison between the bivalve Cerastoderma
      edule and the Polychaete Diopatra neapolitana.
AB  - Metals accumulated in marine sediments are often a threat to benthic communities.
      With the recognized importance and wide use of stress biochemical responses as
      indicators of metal contamination it becomes essential to compare these markers
      between different species and verify their ubiquity and accuracy. Using wild
      Diopatra neapolitana and Cerastoderma edule, collected at several areas differing
      in metal contamination, this study aimed to assess the use of these two
      macrobenthic species as sentinel organisms and to determine the applicability of
      currently used biomarkers in benthic species exposed to a range of low metal and
      As concentrations. Total metal accumulation and intracellular partitioning was
      analyzed and metal-induced alterations were assessed through the analysis of
      several biochemical parameters in both organisms, including stress-induced
      reactive oxygen species (ROS), lipid peroxidation and protein content, the
      activity of antioxidant enzymes catalase (CAT), superoxide dismutase (SOD) and of
      glutathione S-transferase (GST). Metal chelation by Metallothioneins (MTs) was
      also determined. Results revealed that D. neapolitana accumulated higher levels
      of metals when compared to C. edule, independently of the sediment concentration.
      Results also showed strong species-specific responses to metals and differences
      in the ability to sequester metals. Overall, C. edule showed to be more efficient
      metal chelator and precipitatior than D. neapolitana, which was less tolerant and
      presented oxidative stress. MTs proved to be a good predictor of metal
      accumulation in both species, even under low metal exposures. On the other hand,
      lipid peroxidation was a good indicator of oxidative damage, only observed in D.
      neapolitana, which was a result of higher metal retention in the soluble
      fraction.

PMID- 21890203
TI  - An assessment of the genotoxic effects of landfill leachates using bacterial and
      plant tests.
AB  - Two bacterial tests (the Ames test and the umu-test) and the Allium test were
      used to assess the genotoxicity of aqueous leachates from municipal solid waste
      landfill sites in Southern Poland. A comparison of the sensitivity of the applied
      tests was performed. None of the tested samples revealed genotoxic activity in
      the umu-test and thus did not appear to be sensitive enough for evaluations of
      leachates. Two out of 22 leachates were described as genotoxic in the Ames test
      and 3 out of 6 leachates in the Allium test. All of the analyzed leachates
      samples affected cell divisions. Two of the tests applied, the Allium and Ames
      test, revealed the high genotoxicity of leachate 4. Among the bioassays used in
      these studies, the Allium test proved to be more sensitive than bacterial tests
      for the investigation of leachate toxicity. The results suggest that the Allium
      cytogenetic bioassay is efficient and simple for genotoxicity studies of
      leachates. The potential correlations between the chemical characteristics and
      genotoxic effects is discussed. The biological effects of selected appeared to be
      related to chemical parameters. Leachates have a genotoxic potential and pose a
      risk to human health and the environment. A combination of biotests and chemical
      analyses is the best approach for the assessment of the risk or impact of
      leachates.

PMID- 21890204
TI  - Case of interstitial lung disease possibly induced by exposure to iron dust.
AB  - Interstitial lung diseases are primarily attributable to occupational or
      environmental exposures to dusts and irritants. We report on a case of
      interstitial lung disease, possibly secondary to iron exposure. Our male patient
      presented with cough and shortness of breath of more than 20 years' duration
      after his occupational exposure had ended. A chest radiograph showed patchy
      shadows throughout both lower fields, and computed tomography showed ground-glass
      like opacification, with fibrosis in the lower lobes. A lung biopsy revealed
      foamy cells in the alveolar spaces, with bronchiolitis obliterans. Microelemental
      analysis showed an increased level of iron in the lung tissue. After treatment
      with N-acetyl cysteine effervescent tablets, the patient's symptoms gradually
      improved. This probable case of iron-induced interstitial lung disease suggests
      the importance of obtaining a patient's history of occupational and environmental
      exposures for the sake of an accurate diagnosis.

PMID- 21890206
TI  - Assessment of the clinical use of intravenous and oral N-acetylcysteine in the
      treatment of acute acetaminophen poisoning in children: a retrospective review.
AB  - BACKGROUND: N-acetylcysteine (NAC) is the most effective therapy for
      acetaminophen (APAP) toxicity and is currently available for oral and intravenous
      (IV) administration. Although both routes are effective, use of the IV
      formulation has been increasing since becoming available in the United States in
      2004, raising questions about cost/benefit comparisons between the 2
      formulations. Decreased length of treatment and hospital stay have been used to
      justify the use of IV NAC; however, some patients may receive extended therapy of
      either NAC regimen. OBJECTIVE: This retrospective review assessed the clinical
      use of oral and IV NAC in pediatric patients with APAP intoxication from June 1,
      2004 through May 31, 2008. METHODS: Electronic medical charts for patients aged
      <=21 years were identified with International Classification of Diseases, Ninth
      Revision (ICD-9) codes for APAP overdose. Descriptive statistics were used to
      describe the overall patient population and route of NAC administration. The
      primary outcome variable was the length of treatment with IV and oral NAC
      therapy. RESULTS: A total of 62 charts for patients with APAP toxicity were
      reviewed; 37 patients (60%) received IV NAC and 25 patients (40%) received oral
      NAC. The average lengths of treatment and stay for IV dosing were 23.5 hours
      (range, 17.6-54.9 hours) and 1.6 days (range, 1-3 days), respectively; those for
      oral dosing were 69.5 hours (range, 33-133 hours) and 1.95 days (range, 1-5
      days), respectively. Of 16 patients who received oral NAC and were admitted for
      <3 days, 14 were transferred to an inpatient psychiatric unit and completed the
      72-hour therapy. A total of 3 patients received extended NAC dosing-2 with IV
      dosing and 1 with oral dosing. CONCLUSIONS: Based on our review, the majority of
      patients received recommended dosing of NAC therapy; however, 3 patients received
      extended NAC therapy. Patient-specific factors should be considered when
      assessing whether NAC therapy should be extended and if one route of
      administration may be preferred. ClinicalTrials.gov identifier: NCT00725179.

PMID- 21890207
TI  - Spatial and temporal distribution of Pu in the Northwest Pacific Ocean using
      modern coral archives.
AB  - Historical (239)Pu activity concentrations and (240)Pu/(239)Pu atom ratios were
      determined in skeletons of dated modern corals collected from three locations
      (Chuuk Lagoon, Ishigaki Island and Iki Island) to identify spatial and temporal
      variations in Pu inputs to the Northwest Pacific Ocean. The main Pu source in the
      Northwest Pacific is fallout from atmospheric nuclear weapons testing which
      consists of global fallout and close-in fallout from the former US Pacific
      Proving Grounds (PPG) in the Marshall Islands. PPG close-in fallout dominated the
      Pu input in the 1950s, as was observed with higher (240)Pu/(239)Pu atom ratios
      (>0.30) at the Ishigaki site. Specific fallout Pu contamination from the Nagasaki
      atomic bomb and the Ivy Mike thermonuclear detonation at the PPG were identified
      at Ishigaki Island from the (240)Pu/(239)Pu atom ratios of 0.07 and 0.46,
      respectively. During the 1960s and 1970s, global fallout was the major Pu source
      to the Northwest Pacific with over 60% contribution to the total Pu. After the
      cessation of the atmospheric nuclear tests, the PPG again dominated the Pu input
      due to the continuous transport of remobilised Pu from the Marshall Islands along
      the North Equatorial Current and the subsequent Kuroshio Current. The Pu
      contributions from the PPG in recent coral bands (1984 onwards) varied over time
      with average estimated PPG contributions between 54% and 72% depending on
      location.

PMID- 21890208
TI  - Maternal parenting stress and mothers' reports of their infants' mastery
      motivation.
AB  - Mastery motivation is a psychological force that stimulates an individual to
      attempt to master a task that is challenging to him or her. This prospective
      longitudinal study examined the relationship between maternal stress, using the
      Parenting Stress Index-Short Form, and infant mastery motivation, using the
      Dimensions of Mastery Questionnaire, for 150 mother-infant pairs assessed at both
      6- and 18-months of age. Infants of mothers with elevated stress levels at 6
      months tended to show lower mastery motivation at 18 months (standardized beta=
      .46, p=.001). Conversely, infants with lower general competence (standardized
      beta=-.24, p=.021) and lower persistence during social interactions with other
      children (standardized beta=-.18, p=.037) at 6 months of age had mothers with
      elevated total stress at 18 months of age. Implications for programs which
      simultaneously intervene with child and mother are discussed.

PMID- 21890209
TI  - Resilience as a response to the stigma of depression: a mixed methods analysis.
AB  - BACKGROUND: Stigma has been shown to have a significant influence on help
      seeking, adherence to treatment and social opportunities for those experiencing
      depression. There is a need for studies which examine how the stigma of
      depression intersects with responses to depression. METHODS: 161 telephone
      interviews with people experiencing depressive symptoms, derived from a
      longitudinal cohort study, were sampled on the basis of their perceptions of
      stigma around depression. Interview transcripts were searched for references to
      stigma and analysed thematically. The frequency of the themes was calculated and
      cross-referenced, producing a meta-theme matrix. RESULTS: Stigma was closely
      linked to ideas about responsibility for causation and/or continuation of
      depressive symptoms. Stigmatized individuals felt compelled to take steps to
      develop their resilience including drawing on existing support networks and
      expanding on positive emotions and personal strengths in order to counteract this
      stigma. However, such strategies were burdensome for some. These participants
      gained relief from relinquishing their personal responsibility. LIMITATIONS: The
      data were briefer than many interview studies. This narrowed its interpretation,
      but allowed a large sample of participants. CONCLUSIONS: When considering how to
      tailor therapies for those experiencing depressive symptoms, health professionals
      should consider the interaction of stigma with coping strategies. Many
      individuals can build on existing relationships and personal strengths to develop
      resilience, some however need to first relinquish the expectation of having
      sufficient pre-existing resilience within themselves.

PMID- 21890210
TI  - Obstetrical and neonatal outcomes after prenatal exposure to selective serotonin
      reuptake inhibitors: the relevance of dose.
AB  - OBJECTIVE: The purpose of this study was to evaluate the effects of prenatal
      exposure to selective serotonin reuptake inhibitors (SSRIs) on obstetrical and
      neonatal outcomes. METHOD: A case-control study was conducted to compare
      perinatal outcomes among pregnant women with affective disorder (DSM-IV criteria)
      and who received SSRIs during pregnancy with those of women without an active
      psychiatric disorder during pregnancy who were non-exposed to antidepressants
      during pregnancy. Each case was matched to two controls for maternal age (+/- 2
      years) and parity. RESULTS: A total of 252 women were enrolled in the study, 84
      exposed and 168 non-exposed. Demographic and clinical characteristics did not
      differ significantly between the groups. The rates of prelabor rupture of
      membranes, induction of labor and cesarean delivery were slightly higher but not
      statistically significant in the exposed group. The mean gestational age at birth
      was 38.8 (+/- 1.86) weeks for the exposed group and 39.4 (+/- 1.52) weeks for the
      non-exposed group (p=.005). Rates for preterm birth were higher in the exposed
      group (OR=3.44, 95% CI=1.30-9.11). After stratification for dose, it was found
      that exposure to a high-dose was associated with lower gestational age (p=.009)
      and higher rates of prematurity (OR=5.07, 95% CI=1.34-19.23). The differences
      remained significant after controlling for maternal status and the length of
      exposure. CONCLUSION: Women treated with SSRIs during pregnancy, mainly at high
      dose, had an increased risk of preterm birth compared to healthy women of similar
      age and parity who were not exposed to SSRI during pregnancy.

PMID- 21890211
TI  - Mapping the depressed brain: a meta-analysis of structural and functional
      alterations in major depressive disorder.
AB  - BACKGROUND: Depression has a lifetime prevalence of up to 20%. Neuroimaging
      methods have revealed various structural and functional changes that occur in a
      human brain during a depressive episode. However, we still lack information
      concerning the extent to which structural and functional changes co-occur in a
      depressed brain. Furthermore, it is difficult to evaluate from a merely
      qualitative literature review what regional brain changes in volume and
      activation are robust across depressed patient samples and consistent across
      imaging centers. METHODOLOGY AND PRINCIPLE FINDINGS: This study is a meta
      analysis from 10 selected studies published previously. We applied the
      statistical anatomical/activation likelihood estimate method (ALE) in a total of
      176 depressed patients and 175 controls for the MRI modality and in a total of
      102 depressed patients and 94 controls for the PET modality to quantitatively
      identify those brain regions that show concordant alteration in the midst of a
      depressive episode across imaging modalities and study sites. We find a
      convergent change in the limbic-cortical brain circuit in depression compared to
      controls of both Positron Emission Tomography (PET) and Magnetic Resonance
      Imaging (MRI) data. The specific changes include lower gray matter volumes in the
      amygdala, the dorsal frontomedian cortex, and the right paracingulate cortex, as
      well as increases in glucose metabolism in the right subgenual and pregenual
      anterior cingulate cortices. CONCLUSIONS/SIGNIFICANCE: Our current findings
      represent an important first step towards a more focused approach to neuroimaging
      unipolar depression. The regions identified could serve as a specific region-of
      interest-for-disease template for both individual in vivo imaging studies and
      postmortem histopathologic exploration.

PMID- 21890212
TI  - Altered patterns of brain activity during transient sadness in children at
      familial risk for major depression.
AB  - INTRODUCTION: We used functional magnetic resonance imaging (fMRI) to investigate
      the neural correlates of sadness, the prevailing mood in major depression (MD),
      in a prospective, well-documented community sample followed since birth. METHODS:
      The children, comprising 136 children (65 boys and 71 girls) of mothers with
      varying levels of depressive symptomatology, were scanned - using a 1.5-Tesla
      system - while they watched 5 blocks of both sad and neutral film excerpts.
      Following scanning, they rated the emotions they experienced, and if they
      identified sadness, they were also asked to rate its intensity. RESULTS: In
      children whose mothers exhibited higher depressive symptomatology, compared to
      children whose mothers displayed lower depressive symptomatology, altered neural
      responses to sad film excerpts were noted in brain regions known to be involved
      in sadness and MD, notably the insula, anterior cingulate cortex and caudate
      nucleus, even though the children did not differ in current mood. LIMITATIONS:
      Whether this represents genetic vulnerability or a consequence of exposure to
      maternal depressive symptoms at a young age is unknown. DISCUSSION: The results
      are consistent with the results of studies in healthy adults and MD patients. The
      present study suggests that an altered pattern of regional brain responses to sad
      stimuli, is already present in childhood and might represent vulnerability for MD
      later in life.

PMID- 21890213
TI  - Psychological interventions for alcohol misuse among people with co-occurring
      depression or anxiety disorders: a systematic review.
AB  - OBJECTIVE: Depression, anxiety and alcohol misuse frequently co-occur. While
      there is an extensive literature reporting on the efficacy of psychological
      treatments that target depression, anxiety or alcohol misuse separately, less
      research has examined treatments that address these disorders when they co-occur.
      We conducted a systematic review to determine whether psychological interventions
      that target alcohol misuse among people with co-occurring depressive or anxiety
      disorders are effective. DATA SOURCES: We systematically searched the PubMed and
      PsychINFO databases from inception to March 2010. Individual searches in alcohol,
      depression and anxiety were conducted, and were limited to 'human' published
      'randomized controlled trials' or 'sequential allocation' articles written in
      English. STUDY SELECTION: We identified randomized controlled trials that
      compared manual guided psychological interventions for alcohol misuse among
      individuals with depressive or anxiety disorders. Of 1540 articles identified,
      eight met inclusion criteria for the review. DATA EXTRACTION: From each study, we
      recorded alcohol and mental health outcomes, and other relevant clinical factors
      including age, gender ratio, follow-up length and drop-out rates. Quality of
      studies was also assessed. DATA SYNTHESIS: Motivational interviewing and
      cognitive-behavioral interventions were associated with significant reductions in
      alcohol consumption and depressive and/or anxiety symptoms. Although brief
      interventions were associated with significant improvements in both mental health
      and alcohol use variables, longer interventions produced even better outcomes.
      CONCLUSIONS: There is accumulating evidence for the effectiveness of motivational
      interviewing and cognitive behavior therapy for people with co-occurring alcohol
      and depressive or anxiety disorders.

PMID- 21890214
TI  - Impact of employment status and work-related factors on risk of completed
      suicide. A case-control psychological autopsy study.
AB  - The objective of this study was to determine the impact of work-related factors
      on risk for completed suicide. Psychiatric disorders and socio-demographic
      factors including work-related factors were assessed by a semi-structured
      interview using the psychological autopsy method in 163 completed suicide cases
      and by personal interview in 396 living population-based control persons.
      Unemployment (in particular, for more than six months), (early) retirement, or
      homemaker status were associated with highly significantly increased suicide
      risk, independently of categorized psychiatric diagnosis. In addition, adverse
      psychosocial working conditions, such as monotonous work, increased
      responsibility and pronounced mental strain due to contact with work clients,
      significantly increased suicide risk as well, again independently of categorized
      psychiatric diagnosis. These findings demonstrate that negative consequences of
      unemployment, homemaker status with no outside occupation, or (early) retirement,
      as well as adverse psychosocial working conditions, present relevant risk factors
      contributing to suicidal behavior, independently of diagnosed psychiatric
      disorders. Employment and a positive modification of working conditions, may
      possibly be preventive to important adverse mental health outcomes, including
      suicidality.

PMID- 21890215
TI  - No association of polymorphisms in the CDK5, NDEL1, and LIS1 with autism in
      Chinese Han population.
AB  - Autism is a pervasive neurodevelopmental disorder. CDK5 (cyclin-dependent kinase
      5) and its interacting molecules are involved in neurodevelopment. We performed a
      family-based association analysis between CDK5, NDEL1, and LIS1 polymorphisms and
      autism in a Chinese Han population. Our study did not detect a significant
      association. It indicated that common genetic variations in these genes might not
      play a role in the genetic predisposition to autism.

PMID- 21890216
TI  - A reduced incidence of digestive disorders in rabbits is associated with allelic
      diversity at the TLR4 locus.
AB  - Toll-like receptor 4 (TLR4) plays a fundamental role in pathogen recognition and
      activation of host innate immunity. In this study, we detected five coding single
      nucleotide polymorphisms (cSNPs) of the TLR4 gene in New Zealand White rabbits
      and analyzed their associations with genetic resistance against digestive
      disorders based on case-control study (125 cases and 147 controls). The five
      cSNPs included two synonymous mutations (c.57 C>T and c.1098 G>A) and three non
      synonymous mutations (c.566 G>A, c.760 G>A, and c.923 A>G), which totally
      determined two alleles (haplotypes) H1 (the five cSNPs: CGGAG) and H2 (the five
      cSNPs: TAAGA) with pair-wise LD (D') estimates of 1.0. The frequencies of alleles
      and genotypes significantly differed between case group and control group
      (P<0.05). The association analyses revealed that allele H2 carried a potential
      protective role with an odds ratio (OR) value of 0.521 (95% confidence interval
      0.324-0.837, P=0.0064). To our knowledge, this is first report to study the
      genetic polymorphism of TLR4 gene and association with incidence of digestive
      disorders in rabbits.

PMID- 21890217
TI  - Development of a multiplex assay for the detection of antibodies to Borrelia
      burgdorferi in horses and its validation using Bayesian and conventional
      statistical methods.
AB  - Lyme disease is a zoonotic, vector-borne disease and occurs in mammals including
      horses. The disease is induced by infection with spirochetes of the Borrelia
      burgdorferi sensu lato group. Infection of mammalian hosts requires transmission
      of spirochetes by infected ticks during tick bites. Lyme disease diagnosis is
      based on clinical signs, possible exposure to infected ticks, and antibody
      testing which is traditionally performed by ELISA and Western blotting (WB). This
      report describes the development and validation of a new fluorescent bead-based
      multiplex assay for the detection of antibodies to B. burgdorferi outer surface
      protein A (OspA), OspC and OspF antigens in horse serum. Testing of 562 equine
      sera was performed blindly and in parallel by using WB and the new multiplex
      assay. Because a true gold standard is missing for Lyme antibody testing, we
      performed and compared different statistical approaches to validate the new Lyme
      multiplex assay. One approach was to use WB results as a 'relative gold standard'
      in ROC-curve and likelihood-ratio analyses of the new test. Cut-off values and
      interpretation ranges of the multiplex assay were established by the analysis.
      The second statistical approach used a Bayesian model for the calculation of
      diagnostic sensitivities and specificities of the multiplex assay. The Bayesian
      analysis takes into consideration that no true gold standard exists for detecting
      antibodies to B. burgdorferi and estimated sensitivities and specificities of
      both tests that were compared. Therefore, the Bayesian analysis also resulted in
      an evaluation of diagnostic sensitivity and specificity of WB. Overall, the new
      assay was characterized by low background values and a wide dynamic
      quantification range for the detection of antibodies to OspA, OspC and OspF
      antigens of B. burgdorferi. The diagnostic sensitivity and specificity for the
      OspA bead-based assay were calculated as 49% and 85%, respectively, and by a
      standard ROC curve analysis only because the Bayesian model could not be run on
      this parameter. The Bayesian-derived diagnostic sensitivities of the OspC and
      OspF assays were 80% and 86%, respectively. For comparison, the Bayesian-derived
      estimates for WB resulted in sensitivities of 72% for OspC and 80% for OspF. The
      Bayesian diagnostic specificities of the multiplex assay were 79% and 69% for
      OspC and OspF, respectively. WB analysis had specificities of 92% for OspC and
      77% for OspF. Although the analysis of a new assay in the absence of a true gold
      standard remains challenging, the approach used here can help to address this
      problem when new technologies and traditionally used test standards differ
      significantly in their analytical sensitivities, which consequently causes
      problems in the calculation of diagnostic sensitivity and sensitivity values for
      the new assay. In summary, the new multiplex assay for the detection of
      antibodies to B. burgdorferi OspA, OspC and OspF antigens in horse serum has
      improved analytical and diagnostic sensitivities compared to WB analysis.
      Multiplex analysis is a valuable quantitative tool that simultaneously detects
      antibodies indicative for natural infection with and/or vaccination against the
      Lyme pathogen.

PMID- 21890218
TI  - Detection of calprotectin and apoptotic activity within the equine colon from
      horses with black walnut extract-induced laminitis.
AB  - The black walnut extract (BWE) model of equine laminitis is associated with a
      systemic inflammatory response manifest by increased expression of inflammatory
      cytokines in the lungs and liver as well as the laminae. The specific role of the
      gastrointestinal tract in development of this response is unclear and is of
      utmost importance, as gastrointestinal disease and laminitis are intimately
      related. We investigated calprotectin expression and epithelial and endothelial
      apoptosis in the colon of horses exposed to orally administered BWE. Sections of
      colon from 19 horses including 7 controls not exposed to BWE, 6 horses at the
      developmental time-point of leukopenia (DTP) and 6 at the onset of Obel grade 1
      laminitis (LAM) after BWE-administration were histologically examined.
      Immunohistochemical evaluation for calprotectin expression with MAC 387 antibody
      was performed along with assessment of epithelial and endothelial apoptosis with
      caspase-3 active antibody. Calprotectin expression and percentage of apoptotic
      cells were compared between controls and the two treatment groups and presence of
      a correlation between calprotectin expression and apoptosis was evaluated.
      Histological findings from BWE-treated horses included eosinophil and lymphocyte
      epitheliotropism. The DTP group had a higher (p<0.01) calprotectin score with
      respect to the control group, while there was no significant difference in
      percentage of epithelial and endothelial apoptotic cells between groups (p=0.08
      and p=0.48 respectively). No significant correlation was found between
      calprotectin score and epithelial or endothelial apoptosis (p=0.69 and p=0.29
      respectively). There is preliminary evidence that exposure of horses to BWE
      results in an early inflammatory response in the colon. Further studies are
      needed to characterize the nature of the colonic injury in BWE-exposed horses and
      the link to the development of laminitis.

PMID- 21890219
TI  - The role of apoptosis in immunosuppression of dogs with demodicosis.
AB  - The aim of the present study was to evaluate the status of apoptosis in
      peripheral blood leukocytes of dogs with demodicosis. A total of 26 dogs
      suffering from demodicosis, and positive for Demodex canis mites by skin
      scraping, participated in the study, 13 with localized demodicosis (LD) and 13
      with generalized demodicosis (GD). A further 13 clinically healthy dogs, all of
      whom were negative for mites upon skin scraping, were used as controls. The dogs
      with GD revealed significantly higher (P <= 0.0001) percentage of leukocytes with
      externalization of phosphatidylserine (PS) and depolarized mitochondrial membrane
      potentials (DeltaPsim) as compared with the dogs with LD and healthy controls.
      These dogs also revealed significantly lower values (P <= 0.0001) of
      hematological parameters viz. hemoglobin, total erythrocytes count total
      leukocytes count, lymphocytes, monocytes and neutrophils. Significantly higher (P
      <= 0.0001) percentages of leukocytes with externalization of PS and depolarized
      DeltaPsim were also found in dogs with LD as compared with the healthy controls.
      These dogs also revealed significantly lower values of Hb (P <= 0.0001), TEC
      (P=0.025), TLC (P <= 0.0001), lymphocytes (P=0.008), monocytes (P <= 0.0001) and
      neutrophils (P=0.03). It is concluded that premature apoptosis of PBL may be
      implicated in the immunosuppression of the dogs with demodicosis.

PMID- 21890220
TI  - Neuroadaptive changes in cerebellar neurons induced by chronic exposure to IL-6.
AB  - IL-6 is an important signaling molecule in the CNS. CNS neurons express IL-6
      receptors and their signal transduction molecules, consistent with a role for IL
      6 in neuronal physiology. Research indicates that IL-6 levels are low in the
      normal brain but can be significantly elevated in CNS injury and disease.
      Relatively little is known about how the elevated levels of IL-6 affect neurons.
      In the current study we show that under conditions of chronic exposure, IL-6
      induces alterations in the level of protein expression in developing CNS cells.
      Such changes may play a role in the altered CNS function observed in CNS
      conditions associated with elevated levels of IL-6 in the CNS.

PMID- 21890221
TI  - Endoscopic surgery in pediatric recurrent antrochoanal polyp, rule of wide
      ostium.
AB  - OBJECTIVE: To evaluate the use of wide middle meatal antrostomy in recurrent
      antrochoanal polyp (ACP) in children as regard technical difficulty, efficacy,
      and safety in children. STUDY DESIGN: Retrospective study. PATIENTS AND METHODS:
      In a retrospective study, 12 children with unilateral recurrent ACP (5 left
      sided, 7 right-sided). All the ACPs were documented by preoperative endoscopy and
      computer tomographic (CT) scans. All cases were treated using endoscopic wide
      middle meatal antrostomy. The average age at the onset of symptoms was 9.3 years
      (median age: 10 years; range: 6-15 years). RESULTS: Postoperative improvement in
      all cases was achieved using both subjective measures (symptoms improvement) and
      objective measures (radiological and endoscopical). No postoperative
      complications or recurrence during the follow up period. CONCLUSIONS: Endoscopic
      wide middle meatal antrostomy is a useful and easily applicable technique to
      manage recurrent antrochoanal 3 polyp in children. Managing associated pathology
      as turbinate hypertrophy, associated adenoids, anterior ethmoidectomy,
      uncinectomy and endoscopic limited septoplasty should be put in mind in order to
      improve ventilations. Powered instrumentations, angled endoscopes (45 and 70
      degrees ) and angled instrumentations can assure complete clearance of the polyp
      by identifying the origin of polyp in maxillary antrum.

PMID- 21890223
TI  - Metapopulation dynamics and determinants of H5N1 highly pathogenic avian
      influenza outbreaks in Indonesian poultry.
AB  - In 2008, the Indonesian Government implemented a revised village-level
      Participatory Disease Surveillance and Response (PDSR) program to gain a better
      understanding of both the magnitude and spatial distribution of H5N1 highly
      pathogenic avian influenza (HPAI) outbreaks in backyard poultry. To date, there
      has been considerable collection of data, but limited publically available
      analysis. This study utilizes data collected by the PDSR program between April
      2008 and September 2010 for Java, Bali and the Lampung Province of Sumatra. The
      analysis employs hierarchical Bayesian occurrence models to quantify spatial and
      temporal dynamics in backyard HPAI infection reports at the District level in 90
      day time periods, and relates the probability of HPAI occurrence to PDSR-reported
      village HPAI infection status and human and poultry density. The probability of
      infection in a District was assumed to be dependent on the status of the District
      in the previous 90 day time period, and described by either a colonization
      probability (the probability of HPAI infection in a District given there had not
      been infection in the previous 90 day time period) or a persistence probability
      (the probability of HPAI infection being maintained in the District from the
      previous to current 90 day period). Results suggest that the number of
      surveillance activities in a district had little relationship to outbreak
      occurrence probabilities, but human and poultry densities were found to have non
      linear relationships to outbreak occurrence probabilities. We found significant
      spatial dependency among neighboring districts, indicating that there are latent
      spatial processes that are not captured by the covariates available for this
      study, but which nonetheless impact outbreak dynamics. The results of this work
      may help improve understanding of the seasonal nature of H5N1 in poultry and the
      potential role of poultry density in enabling endemicity to occur, as well as to
      assist the Government of Indonesia target scarce resources to regions and time
      periods when outbreaks of HPAI in poultry are most likely to occur.

PMID- 21890222
TI  - Survey disability questionnaire does not generate valid accurate data compared to
      clinical assessment on an older population.
AB  - PURPOSE: Policy-makers and health care managers need accurate information on
      disabilities in the population to plan appropriate services to the older
      population. Disability information from population surveys are often very crude
      as compared to information used on the clinical field. This study aimed to verify
      the concurrent validity of a survey questionnaire version of a disability
      instrument (SMAF) administered by lay interviewers, compared to the original SMAF
      rating scale completed by clinicians. METHODS: The survey questionnaire version
      was developed by a panel of experts and pretested with 15 patients attending a
      day hospital program using a think-aloud approach. A social worker administered
      the SMAF rating scale at home to a sample of Community-dwelling frail people over
      81 years old who participated in the PRISMA longitudinal study in Sherbrooke,
      Quebec, Canada. The same subjects were contacted one month later by a lay
      interviewer, who completed the survey questionnaire. The two versions were
      compared using intraclass correlation coefficients (ICCs) and weighted kappas
      (WK). RESULTS: 96 subjects participated in the study. The ICC was 0.82 for the
      total SMAF score and ranged from 0.46 (mental functions) to 0.82 (IADL) for the
      subscores. The questionnaire version systematically underestimated disability by
      4.7 points on average (out of 87) (p<0.0001). For the case-mix classification
      generated from the disability assessment (Iso-SMAF profiles), the underestimation
      was even more striking. CONCLUSIONS: A survey questionnaire is not a valid method
      for accurately estimating disability in a population.

PMID- 21890224
TI  - Image-guided radiotherapy using surgical clips as fiducial markers after
      prostatectomy: a report of total setup error, required PTV expansion, and
      dosimetric implications.
AB  - PURPOSE: To determine the total setup error and the required planning target
      volume (PTV) margin for prostate bed without image guided radiotherapy (IGRT),
      and to demonstrate the feasibility and dosimetric benefit of IGRT post
      prostatectomy using surgical clips. MATERIALS AND METHODS: Seventeen patients
      were treated with intensity modulated radiotherapy (IMRT) to the prostate bed
      with a 1cm PTV margin. Three-dimensional shifts of the surgical clips inside the
      prostate bed were measured with respect to the isocenter from 364 orthogonal kV
      image pairs, and the total setup error was calculated to determine the required
      PTV margin. Alternative IMRT plans using 5mm or 1cm PTV expansion were generated
      and compared for rectal and bladder sparing. RESULTS: Surgical clips were
      reproducibly and reliably identified. The mean (standard deviation) shifts in the
      left-right (LR), superior-inferior (SI), and anterior-posterior (AP), axes were: 
      0.1 mm (1.7 mm), 0.6 mm (2.4 mm), and -2.1 mm (2.6 mm), respectively. The
      required PTV margins were calculated to be 6, 8, and 9 mm in the LR, AP, and SI
      axis, respectively. A PTV expansion of 5mm, compared to 1cm, significantly
      reduced V65 Gy to the rectum by 10%. CONCLUSIONS: In the absence of IGRT, a non
      uniform PTV margin of 6mm LR, 8mm AP, and 9 mm SI should be considered. Use of
      clips as fiducial markers can decrease the total setup error, enable a smaller
      PTV margin, and improve rectal sparing.

PMID- 21890225
TI  - Phase I study of radiochemotherapy with gemcitabine in invasive bladder cancer.
AB  - Tolerability to gemcitabine radiochemotherapy was evaluated in 33 patients with
      inoperable, locally advanced transitional-cell bladder cancers. The dose of 75
      mg/m(2) gemcitabine once a week, concurrently with standard radiotherapy of 60
      Gy/6 weeks, was found to be acceptable. Eighty-one percentage of 3-year local
      progression-free survival suggests efficiency warranting further studies.

PMID- 21890226
TI  - Aerobic and resistance training effects compared to aerobic training alone in
      obese type 2 diabetic patients on diet treatment.
AB  - AIMS: The study was designed to compare a combined aerobic and resistance
      training (ART) with an aerobic training (AT) over hemodynamic, glucose metabolism
      and endothelial factors, adipokines and pro-inflammatory marker release in a
      population of obese type 2 diabetic patients. METHODS: Forty-seven patients were
      randomly assigned to aerobic (27 patients) or aerobic plus resistance (20
      patients) exercise trainings, on the top of a diet regime. Anthropometric,
      metabolic, hormonal and inflammatory variables were measured at hospitalization
      and discharge. RESULTS: Both exercise programs equally improved body weight and
      fructosamine levels however ART only partially decreased HOMA index compared with
      AT (ART: -25% vs AT: -54%, p<0.01). Mean blood pressure (AT: -3.6 mmHg vs ART:
      +0.6 mmHg, p<0.05) and endothelin-1 (ET-1) incremental areas during walking test
      (AT: -11% vs ART: +30%, p<0.001) decreased after AT while increased after ART.
      Adiponectin levels increased by 54% after AT while decreased by 13% after ART
      (p<0.0001) and matrix metalloproteinase-2 (MMP-2), tumor necrosis factor-alpha
      (TNF-alpha) and monocyte chemoattractan protein-1 (MCP-1) levels significantly
      decreased in AT while increased in ART group. CONCLUSIONS: Compared with AT, ART
      similarly enhanced body weight loss but exerted less positive effects on insulin
      sensitivity and endothelial factors, adipokines and pro-inflammatory marker
      release.

PMID- 21890227
TI  - Temporal changes in the prevalence of diabetes, impaired fasting glucose and its
      associated risk factors in the rural area of Baluchistan.
AB  - AIMS: To observe temporal changes in the prevalence of diabetes, impaired fasting
      glucose and its associated risk factors in the rural area of Baluchistan province
      of Pakistan according to American Diabetes Association criteria by comparing the
      two surveys done in 2002 and 2009. METHODOLOGY: This community based survey of
      1264 subjects aged 25 years and above was conducted from February 2009 to
      February 2010 in sixteen villages of southern Baluchistan. The temporal changes
      were assessed in comparison with a similar survey conducted seven years
      previously. Data from 2002 survey was also re-analyzed according to the latest
      ADA criteria. RESULTS: A two-fold increase in the prevalence of diabetes (from
      7.2% to 14.2%) was seen in 2009 survey and the prevalence of impaired fasting
      glucose also increased significantly (6.5-11.0%). An important finding was the
      number of hypertensives and subjects with positive family history of diabetes
      also increased significantly (p<0.000) from the previous survey. CONCLUSION:
      Coordinated National Programs for primary prevention to counteract the increasing
      prevalence of diabetes are the need of time. Further large scale studies with
      proper risk factor assessment are needed to ascertain the reasons of rising
      prevalence of glucose intolerance.

PMID- 21890228
TI  - Safety and effectiveness of pemetrexed in patients with malignant pleural
      mesothelioma based on all-case drug-registry study.
AB  - BACKGROUND: Pemetrexed in combination with cisplatin (Pem/Cis) is the only
      approved chemotherapeutic regimen for malignant pleural mesothelioma (MPM). At
      the time of launch, limited safety information was available. The purpose of this
      postmarketing all-case registry study was to investigate the safety and
      effectiveness of pemetrexed in patients with MPM. METHODS: From January 2007 to
      May 2008, MPM patients to be treated with pemetrexed in Japan were registered to
      this study to monitor its safety and effectiveness. Supply of pemetrexed was
      restricted to institutions with experienced medical oncologists based on
      predetermined criteria. RESULTS: Of 953 patients registered, data from 903
      patients were eligible for analysis. Most patients were male, with median age of
      65 years and 68.5% had a history of asbestos exposure. More than 90% of patients
      received the first cycle of Pem/Cis treatment; median number of treatment cycles
      was 4.0. Treatment-associated death was reported in 0.8% of patients. The
      incidence of Interstitial lung disease (ILD) associated with Pem/Cis during the
      observation period was 0.9%. The frequency of ILD in patients with pre-existing
      asbestosis was higher than that in patients without it. For tumor response, the
      overall response rate was 25.0% (95% confidence interval (CI): 22.2-28.0%). The
      six-month survival rate estimated by the Kaplan-Meier method was 75.9%.
      CONCLUSIONS: This large scale all case registry study appeared to have enrolled a
      major portion of Japanese MPM patients. Treatment with pemetrexed was generally
      well tolerated and showed safety and effectiveness comparable to prior clinical
      trials.

PMID- 21890229
TI  - Correlation between tumor measurement on Computed Tomography and resected
      specimen size in lung adenocarcinomas.
AB  - OBJECTIVE: To compare preoperative size of stage I and stage II lung
      adenocarcinoma as measured by Computed Tomography (CT) and as assessed on gross
      pathology specimens. MATERIALS AND METHODS: 47 patients diagnosed with stage I or
      II lung adenocarcinoma were evaluated. Institutional Review Board permission was
      obtained. Tumor contours were delineated using a semi-automated segmentation
      algorithm and adjusted based on a radiologist's input. Based on the tumor
      perimeter, maximal in-plane tumor diameter was calculated automatically. The
      largest single diameter from the pathology gross report was utilized. A paired t
      test was used to examine the measurement difference between CT and pathology.
      RESULTS: The mean largest diameter of the tumors at CT and pathology was 29.53 mm
      and 24.04 mm, respectively. There was a statistically significant difference
      between the mean CT measurement and mean pathology measurement of 5.49 mm
      (standard deviation 9.08 mm, p<0.001). The percent relative difference between
      the two measurements was 18.3% (standard deviation 28.2%). CONCLUSION: There is a
      statistically significant difference between the tumor diameter as measured by CT
      and on pathology gross specimen. These differences could have implications in the
      treatment and prognosis of patients with early stage lung adenocarcinoma.

PMID- 21890230
TI  - The evolution and significance of male mate choice.
AB  - The distinct reproductive roles of males and females, which for many years were
      characterised in terms of competitive males and choosy females, have remained a
      central focus of sexual selection since Darwin's time. Increasing evidence now
      shows that males can be choosy too, even in apparently unexpected situations,
      such as under polygyny or in the absence of male parental care. Here, we provide
      a synthesis of the theory on male mate choice and examine the factors that
      promote or constrain its evolution. We also discuss the evolutionary significance
      of male mate choice and the contrasts in male versus female mate choice. We
      conclude that mate choice by males is potentially widespread and has a distinct
      role in how mating systems evolve.

PMID- 21890231
TI  - Applications and implications of direct groundwater velocity measurement at the
      centimetre scale.
AB  - Three projects involving point velocity probes (PVPs) illustrate the advantages
      of direct groundwater velocity measurements. In the first, a glacial till and
      outwash aquifer was characterized using conventional methods and multilevel PVPs
      for designing a bioremediation program. The PVPs revealed a highly conductive
      zone that dominated the transport of injected substances. These findings were
      later confirmed with a natural gradient tracer test. In the second, PVPs were
      used to map a groundwater velocity field around a dipole recirculation well. The
      PVPs showed higher than expected velocities near the well, assuming homogeneity
      in the aquifer, leading to improved representations of the aquifer heterogeneity
      in a 3D flow model, and an improved match between the modelled and experimental
      tracer breakthrough curves. In the third study, PVPs detected subtle changes in
      aquifer permeability downgradient of a biostimulation experiment. The changes
      were apparently reversible once the oxygen source was depleted, but in locations
      where the oxygen source lingered, velocities remained low. PVPs can be a useful
      addition to the hydrogeologist's toolbox, because they can be constructed
      inexpensively, they provide data in support of models, and they can provide
      information on flow in unprecedented detail.

PMID- 21890232
TI  - A socio-ecological adaptive approach to contaminated mega-site management: from
      'control and correct' to 'coping with change'.
AB  - Mega-sites have a notable impact on surrounding ecological systems. At such sites
      there are substantial risks associated with complex socio-ecological interactions
      that are hard to characterize, let alone model and predict. While the urge to
      control and clean-up mega-sites (control and correct) is understandable, rather
      than setting a goal of cleaning up such sites, we suggest a more realistic
      response strategy is to address these massive and persistent sources of
      contamination by acknowledging their position as new features of the socio
      ecological landscapes within which they are located. As it seems nearly
      impossible to clean up such sites, we argue for consideration of a 'coping with
      change' rather than a 'control and correct' approach. This strategy recognizes
      that the current management option for a mega-site, in light of its physical
      complexities and due to changing societal preferences, geochemical
      transformations, hydrogeology knowledge and remedial technology options may not
      remain optimal in future, and therefore needs to be continuously adapted, as
      community, ecology, technology and understanding change over time. This approach
      creates an opportunity to consider the relationship between a mega-site and its
      human and ecological environments in a different and more dynamic way. Our
      proposed approach relies on iterative adaptive management to incorporate mega
      site management into the overall socio-ecological systems of the site's context.
      This approach effectively embeds mega-site management planning in a triple bottom
      line and environmental sustainability structure, rather than simply using single
      measures of success, such as contaminant-based guidelines. Recognizing that there
      is probably no best solution for managing a mega-site, we present a starting
      point for engaging constructively with this seemingly intractable issue.
      Therefore, we aim to initiate discussion about a new approach to mega-site
      management, in which the complexity of the problems posed by mega-sites is
      reflected upon in its entirety. These complexities are associated with
      uncertainties and unknowns that have to be addressed, as they have an impact on
      the strategies being developed and applied. We contend that the best that can be
      hoped for in mega-site management is an acceptable solution for the current state
      of affairs, with good flexibility to modify strategies as new site conditions,
      remediation possibilities, community preferences and management objectives
      develop over time.

PMID- 21890233
TI  - [Intraocular foreign bodies (IOFB) of the posterior segment: retrospective
      analysis and management of 57 cases].
AB  - PURPOSE: To determine the influence of prognostic factors and the type of
      tamponade agent in surgical management of intraocular foreign bodies (IOFBs) for
      better visual outcome. PATIENTS AND METHODS: Fifty-seven consecutive cases were
      retrospectively reviewed at the XV-XX National Hospital (Paris) between 1 January
      2004 and 31 December 2007. Univariate and multivariate analyses were performed to
      identify prognostic variables. Several parameters were measured: pre- and
      postoperatively: best corrected visual acuity (BCVA), material and size of the
      foreign body, entry site, time from trauma to surgical removal, IOFB location,
      initial retinal detachment, choice of vitreous tamponade agent (none, gas,
      silicone oil), postoperative visual outcome, and complications (siderosis,
      endophthalmitis, and vitreoproliferative retinal detachment). RESULTS: Metal
      IOFBs accounted for the majority with 80.7% (n=46). The inferior retinal segment
      was the most frequent location found: 47.4% (n=27). Initial and final mean BCVAs
      were, respectively, 1.47 (+/-0.99) and 1.03 (+/-0.96) (LogMar scale). The mean
      follow-up was 20.7 months (range, 12-60 months). Initial retinal detachment was
      found in 24.56% (n=14), with a statically worse prognosis. The BCVA was better in
      the group with gas tamponade (n=16) than in the group with silicone tamponade
      (n=21) and the group without a tamponade agent (n=20). Initial BCVA was the most
      important predictive factor for final BCVA. Time to surgery was a predictive
      factor of final visual outcome with a cut-off in the first week. The scleral or
      corneoscleral entry site had a better prognosis than the corneal site. Five cases
      of siderosis (8.7%) related to delayed management and two cases of
      endophthalmitis (3.5%) were found (despite use of prophylactic systemic
      antibiotics). No statistical difference was found regarding the IOFB location on
      the retina, its size, or the material. Finally, the retina remained detached in
      nine cases (15.78%). A final BCVA of 20/40 or more was obtained in 39.3 and 17.5%
      had light perception or worse. CONCLUSION: The prognosis of an IOFB injury is for
      the most part uncertain due to a complex combination of parameters. Nevertheless,
      good postoperative results can be achieved without a silicone tamponade agent.
      The main prognostic factors related to better visual outcome were initial BCVA,
      time to surgery (first week), initially attached retina, and the scleral entry
      site. The main complications were vitreoproliferative retinal detachment,
      endophthalmitis, and siderosis. The location, type, and size of IOFBs were not
      statistically significant predictive factors in this study.

PMID- 21890234
TI  - Children's sun exposure and sun protection: prevalence in Australia and related
      parental factors.
AB  - BACKGROUND: Reducing childhood exposure to ultraviolet radiation is important to
      minimize lifetime skin cancer risk. OBJECTIVES: We sought to describe the
      prevalence of children's sun-related behaviors and associated parental and other
      factors. METHODS: In weekly cross-sectional telephone interviews during summer,
      1140 parents/guardians of children aged 0 to 11 years were recruited. Parents
      provided proxy reports for one of their children. Key questions related to
      weekend sun protection and sunburn, parent's sun-related attitudes, and
      demographic characteristics. Potential predictors of children's sun protection
      and sunburn were analyzed adjusting for covariates including weather conditions
      on the previous weekend. RESULTS: On summer weekends, 73% of children spent
      longer than 15 minutes outdoors in peak ultraviolet radiation periods. Of these,
      64% were protected by a hat and 58% by sun-protection factor 15 or higher
      sunscreen, 32% stayed under shade, and 18% wore three-quarter or long-sleeved
      tops. Overall, 8% of children had sunburn. Parental attitudes were typically
      supportive of children's sun protection. Parental use of hats (odds ratio [OR]
      3.1; 95% confidence interval [CI] 1.6-6.2), shade (OR 9.6; 95% CI 4.4-20.8),
      sunscreen (OR 12.6; 95% CI 5.2-30.4), longer leg cover (OR 10.3; 95% CI 4.4
      24.0), and two or more protective behaviors (OR 5.7; 95% CI 2.8-11.9) increased
      the odds of their children practicing these behaviors, as did some parental
      attitudes. LIMITATIONS: We relied on cross-sectional parent reports. CONCLUSION:
      Although children's sun protection was favorable, there was room for improvement.
      Health promotion to improve sun-protection practices in adults may benefit
      children's sun-safe behaviors.

PMID- 21890235
TI  - Common complementary and alternative therapies with potential use in dermatologic
      surgery: risks and benefits.
AB  - BACKGROUND: Ambulatory surgery patients often use complementary and alternative
      medicine (CAM) therapies. CAM therapies may create beneficial and detrimental
      perioperative conditions. OBJECTIVE: We sought to improve knowledge of CAM
      effects in dermatologic surgery, allowing dermatologists to potentially
      capitalize on therapeutic actions and to mitigate complications. METHODS: PubMed
      literature search of CAM therapies in dermatologic and surgical settings was
      performed. Common CAM therapies with possible effects on dermatologic surgery
      were selected. Beneficial and detri-mental effects were reviewed. RESULTS: A
      myriad of products may be used perioperatively by the patient. Therapies
      appearing to have some evidence for potential benefit include bromelain, honey,
      propolis, arnica, vitamin C and bioflavonoids, chamomile, aloe vera gel, grape
      seed extract, zinc, turmeric, calendula, chlorella, lavender oil, and gotu kola.
      Potential complications vary according to product and include platelet
      inhibition, contact dermatitis and, in rare cases, systemic toxicity.
      LIMITATIONS: This review focuses on CAM having significant published studies
      evaluating efficacy for wound healing, anti-inflammatory, antipurpuric, or
      perioperative-related use. Most published studies have been small and often have
      design flaws. The scope of CAM is large and not all therapies are discussed.
      CONCLUSION: Selected CAM therapies have been reported to promote wound healing,
      reduce edema or purpura, and provide anti-inflammatory effects. Because of high
      rates of CAM use, surgeons should familiarize themselves with common uses,
      potential benefits, and complications. Further study of effects in the
      dermatologic surgery setting may improve the patient-doctor relationship and
      enhance outcomes.

PMID- 21890236
TI  - Patient-centered online management of psoriasis: a randomized controlled
      equivalency trial.
AB  - BACKGROUND: Previous research suggests that technology-enabled health care
      delivery may improve access to dermatologic specialty care. Outcomes research
      using validated outcomes measures is necessary for evaluation of novel health
      care delivery models. OBJECTIVE: We sought to compare the clinical equivalence of
      a novel patient-centered online health care delivery model with standard in
      office care for follow-up treatment of patients with psoriasis. METHODS: A total
      of 64 participants with psoriasis were randomized to receive follow-up care
      either in-office or online over a 24-week period. Patients randomized to the
      online group underwent standardized training on capturing high-quality digital
      images of their psoriatic skin and transmitting these images and clinical history
      to a dermatologist securely. The dermatologist then performed asynchronous,
      online evaluation and provided recommendations directly to patients. We used
      clinically validated disease severity and quality-of-life measures to assess
      effectiveness between the models. RESULTS: Both online and in-office groups
      showed improvement in psoriasis disease severity as measured by mean improvement
      in Psoriasis Area and Severity Index (online group: mean = -3.4, in-office: mean
      = -3.4). Patient-centered online care resulted in similar improvement in
      psoriasis severity compared with in-person follow-up care (mean difference in
      Psoriasis Area and Severity Index change 0.1, 95% confidence interval -2.2 to
      2.3, a priori equivalence margin of 2.5). Investigator Global Assessment and
      Dermatology Life Quality Index scores also improved during the study period; no
      significant differences existed between the two groups. LIMITATIONS: The follow
      up period was limited to 24 weeks. CONCLUSION: A patient-centered online model
      may be an effective alternative to in-office care for follow-up management of
      psoriasis.

PMID- 21890237
TI  - Selective use of computed tomography compared with routine whole body imaging in
      patients with blunt trauma.
AB  - STUDY OBJECTIVE: Routine pan-computed tomography (CT, including of the head,
      neck, chest, abdomen/pelvis) has been advocated for evaluation of patients with
      blunt trauma based on the belief that early detection of clinically occult
      injuries will improve outcomes. We sought to determine whether selective imaging
      could decrease scan use without missing clinically important injuries. METHODS:
      This was a prospective observational study of 701 patients with blunt trauma at
      an academic trauma center. Before scanning, the most senior emergency physician
      and trauma surgeon independently indicated which components of pan-CT were
      necessary. We calculated the proportion of scans deemed unnecessary that: (a)
      were abnormal and resulted in a pre-defined critical action or (b) were abnormal.
      RESULTS: Pan-CT was performed in 600 of the patients; the remaining 101 underwent
      limited scanning. One or both physicians indicated a willingness to omit 35% of
      the individual scans. An abnormality was present in 18% of scans, including 22%
      of desired scans and 10% of undesired scans. Among the 95 patients who had one of
      the 102 undesired scans with abnormal results, 3 underwent a predefined critical
      action. There is disagreement among the authors about the clinical significance
      of the abnormalities found on the 99 undesired scans that did not lead to a
      critical action. CONCLUSION: Selective scanning could reduce the number of scans,
      missing some injuries but few critical ones. The clinical importance of injuries
      missed on undesired scans was subject to individual interpretation, which varied
      substantially among authors. This difference of opinion serves as a microcosm of
      the larger debate on appropriate use of expensive medical technologies.

PMID- 21890238
TI  - Viral study on a ventilation filter from a public building.

PMID- 21890239
TI  - Self-administered preoperative antiseptic wash to prevent postoperative infection
      after deep brain stimulation.
AB  - BACKGROUND: Prevention of surgical site infections is critical in deep brain
      stimulation (DBS). In the present study, we tested the ability of a self
      administered preoperative alcohol-based (70% ethyl alcohol) preparation to reduce
      the rate of postoperative infection after DBS surgery. METHODS: This
      Institutional Review Board-approved retrospective review was conducted at our
      institution between January 2005 and October 2007 (mean follow-up, 23 months).
      The participants comprised a consecutive sample of 172 patients with movement
      disorders who underwent DBS surgery at our institution. Starting in January 2007,
      all patients were required to use the alcohol-based preparation. These patients
      (n = 48) were instructed to self-administer the wash on the night before surgery
      and the morning of surgery. Before this time, no self-administered wash was used
      (n = 122). RESULTS: There was no difference in preoperative skin cleansing
      between the 2 groups, and all patients received intravenous antibiotics
      immediately before and after surgery for 24 hours. We compared the rate of
      postoperative infection in the 2 groups and reviewed other possible factors
      underlying infection. We found 11 cases of infection (6.47%), all in the group
      without the preoperative antiseptic wash. The infection rate was 9.02% in the
      group without the preoperative wash and 0 in the group with the preoperative wash
      (P < .029). There was no difference between the 2 groups in terms of mean age,
      duration of operative procedure, or number of microelectrode tracts attempted.
      CONCLUSIONS: Our results support the incorporation of this self-administered
      antiseptic wash into our standard antiseptic protocol for patients undergoing DBS
      surgery.

PMID- 21890240
TI  - ["Time is brain": only in the acute phase of stroke?].
AB  - INTRODUCTION AND OBJECTIVE: In Spain, stroke is the leading cause of death in
      women as well as the leading cause of disability in adults. This translates into
      a huge human and economic cost. In recent years there have been significant
      advances both in the treatment of acute stroke and in the neuro-rehabilitation
      process; however, it is still unclear when the best time is to initiate
      neurorehabilitation and what the consequences of delaying treatment are. To test
      the effect of a single day delay in the onset of neurorehabilitation on
      functional improvement achieved, and the influence of that delay in the rate of
      institutionalisation at discharge. METHODS: A retrospective study of patients
      admitted to Parkwood Hospital's Stroke Neurorehabilitation Unit (UNRHI)
      (University of Western Ontario, Canada) between April 2005 and September 2008 was
      performed. We recorded age, Functional Independence Measurement (FIM) score at
      admission and discharge, the number of days between the onset of stroke and
      admission to the Neurorehabilitation Unit and discharge destination. RESULTS:
      After adjustment for age and admission FIM, we found a significant association
      between patient functional improvement (FIM gain) and delay in starting
      rehabilitation. We also observed a significant correlation between delay in
      initiating therapy and the level of institutionalisation at discharge.
      CONCLUSIONS: A single day delay in starting neurorehabilitation affects the
      functional prognosis of patients at discharge. This delay is also associated with
      increased rates of institutionalisation at discharge.

PMID- 21890242
TI  - Schizencephaly: a study of 16 patients.
AB  - OBJECTIVE: To present 16 patients with schizencephaly and neurological
      involvement, and analyse their characteristics and neuroimages. MATERIAL AND
      METHODS: The study included 16 patients, 8 males and 8 females, all of whom were
      diagnosed with schizencephaly at less than 3 years of age; 2 patients were
      diagnosed prenatally. Schizencephaly was identified by computerized tomography
      (CT) in 1 patient and by MR or three-dimensional MR (3DMR) with a 1.5tesla
      apparatus in the others. Most patients were referred for evaluation because of
      psychomotor delay, motor disabilities and/or seizures. RESULTS: Five patients had
      bilateral schizencephaly with open lips (2 of them had suffered intrauterine
      cytomegalovirus infections); 2 showed unilateral schizencephaly with separated
      lips, 8 presented unilateral schizencephaly with fused lips, and 1 had
      schizencephaly with open lips on one side and fused lips on the other. Prenatal
      cytomegalovirus infection was diagnosed in 2 patients. A cerebral malformation
      that affected the midline was diagnosed by routine ultrasound studies in 2
      patients. Eight patients (50%) presented with seizures that were focal, except
      for one patient who showed secondary generalisation. The latter was the only
      patient whose disease was refractory to complete seizure control with
      antiepileptic medication. All patients had some degree of motor deficit, which
      was either unilateral (hemiparesis) or bilateral (tetraparesis). CONCLUSION: 3D
      MR imaging was very important in diagnosing of schizencephaly in our patients
      because it showed the polymicrogyria that covered the area of the cleft and
      permitted us to rule out porencephaly. Neuronal migration disorders such as
      heterotopias and, more frequently, cortical dysplasias, were observed in several
      patients. Half of the patients had epilepsy which was controlled with
      antiepileptic medication, except in 1 patient.

PMID- 21890243
TI  - Interhemispheric lipoma associated with agenesis of the corpus callosum.

PMID- 21890244
TI  - [Trafficking of women for sexual exploitation: the role of the health sector].

PMID- 21890241
TI  - Guidelines for the preventive treatment of ischaemic stroke and TIA (I). Update
      on risk factors and life style.
AB  - OBJECTIVE: To update the ad hoc Committee of the Cerebrovascular Diseases Study
      Group of The Spanish Neurological Society guidelines on prevention of ischaemic
      stroke (IS) and transient ischaemic attack (TIA). METHODS: We reviewed available
      evidence on risk factors and means of modifying them to prevent ischaemic stroke
      and TIA. Levels of evidence and recommendation grades are based on the
      classification of the Centre for Evidence-Based Medicine. RESULTS: This first
      section summarises the recommendations for action on the following factors: blood
      pressure, diabetes, lipids, tobacco and alcohol consumption, diet and physical
      activity, cardio-embolic diseases, asymptomatic carotid stenosis, hormone
      replacement therapy and contraceptives, hyperhomocysteinemia, prothrombotic
      states and sleep apnea syndrome. CONCLUSIONS: Changes in lifestyle and
      pharmacological treatment for hypertension, diabetes mellitus and dyslipidemia,
      according to criteria of primary and secondary prevention, are recommended for
      preventing ischemic stroke.

PMID- 21890245
TI  - Synthesis and anti-microbial activity of some 1- substituted amino-4,6-dimethyl-2
      oxo-pyridine-3-carbonitrile derivatives.
AB  - A new series of 1- substituted amino-4,6-dimethyl-2-oxo-pyridine-3-carbonitrile
      such as hydrazide hydrazones 3a-h; ethane-1,2-diaminopyridine 6;
      phthalimidopyridines 8a,b; hydrazides 10a,b; urea 11a and thiourea 11b were
      synthesized in a good to excellent yield in step efficient process, using 1-amino
      4,6-dimethyl-2-oxo-1,2-dihydropyridine-3-carbonitrile (1) as a key intermediate.
      The antibacterial and antifungal activities of the synthesized compounds were
      evaluated. The obtained data indicated that the majority of the tested compounds
      exhibited both antibacterial and antifungal activities, particularly compounds 8a
      and 8b showed a comparable effect to a well known antibacterial and antifungal
      agents.

PMID- 21890247
TI  - Design, synthesis and evaluation of PEGylated lipoic acid derivatives with
      functionality as potent anti-melanogenic agents.
AB  - The novel PEGylated lipoic acid (LA) derivatives with functionality were
      synthesized in satisfactory yield by simple procedures and evaluated about its
      anti-melanogenic activity on the B16F10 melanoma cells. Grafting a PEG moiety
      onto the carboxyl group of LA has reduced the cell cytotoxicity and provided the
      water solubility and functionality to incorporate the other bioactive moieties.
      We have found that derivatives showed inhibition of melanin formation by up to
      36.5% at 0.1 mM, whereas LA decreased the melanin formation by 8.6%. In addition,
      it also inhibits at least 86.4% UV-induced MMP-1 expression at 0.1 mM which is
      higher than LA. These data suggest that the novel PEGylated LA derivatives with
      functionality may thus serve as a potentially effective anti-melanogenic and anti
      aging agent.

PMID- 21890246
TI  - Polymeric systems containing dual biologically active ions.
AB  - This paper reports the synthesis and characterization of dual functional
      polymerizable salts containing quaternary ammonium cations ionically linked to
      non steroidal anti-inflammatory drugs (NSAIDs), and their polymers and
      copolymeric systems obtained with acrylic monomers of different hydrophilicity,
      e.g. methyl methacrylate and 2-hydroxyethyl methacrylate. NSAIDs used were
      meclofenamic acid, ketoprofen and ibuprofen. Sustained release of the NSAID from
      polymeric and copolymeric samples was observed over a period of 10 days and the
      hydrophobic/hydrophilic character of both the polymeric system and the drug
      played a role in the release behaviour. The antimicrobial activity of dual
      functional monomeric and polymeric derivatives was confirmed against Gram
      positive and Gram-negative bacteria and polymeric compounds presented higher
      bactericidal action than the precursory monomers. The extracts of copolymeric
      samples had anti-inflammatory activity in a nitric oxide inhibitory assay on RAW
      264.7 cells and they produced a NO inhibition around 80% within the first seven
      days.

PMID- 21890248
TI  - Anticancer and radio-sensitizing evaluation of some new thiazolopyrane and
      thiazolopyranopyrimidine derivatives bearing a sulfonamide moiety.
AB  - Recently, it has been reported that compounds bearing a sulfonamide moiety posses
      many types of biological activities, including anticancer activity. There are a
      variety of mechanisms for their anticancer activity, and the most prominent
      mechanism is the inhibition of carbonic anhydrase (CA) isozymes. The present work
      reports the synthesis of some new thiazolo[4,5-b]pyrane, thiazolo[4,5
      b]pyrano[2,3-d]pyrimidine derivatives bearing a sulfonamide moiety. The design of
      the structures of these compounds complies with the general pharmacophoric
      requirements for CA inhibiting anticancer drugs. The newly synthesized compounds
      were evaluated for their in vitro anticancer activity against human breast cancer
      cell line (MCF7). Most of the screened compounds showed interesting cytotoxic
      activities compared to doxorubicin as a reference drug. Compounds 5, 6, 10 and 12
      (IC(50) values 39.4 MUM, 41.6 MUM, 35.72 MUM and 34.64 MUM, respectively)
      exhibited higher cytotoxic activities than the reference drug doxorubicin (IC(50)
      = 71.8 MUM). Additionally, the previously mentioned compounds were evaluated
      again for their ability to enhance the cell killing effect of gamma-radiation.

PMID- 21890249
TI  - [Practical role of neuro-immunology in the diagnosis and management of peripheral
      neuropathies].
AB  - Anti-glycolipid antibodies have emerged since a decade as a useful tool in the
      diagnosis of inflammatory neuropathies. These autoantibodies target various
      Schwann cells antigens, and are characterized by modest specificity and
      sensitivity, complex nomenclature and cross-reactions. For all these reasons, the
      use of anti-glycolipid antibodies measurement may be confusing. In this article,
      we describe the clinical manifestations associated with anti-glycolipid
      antibodies and propose guidelines for indication and interpretation of anti
      glycolipids measurement.

PMID- 21890250
TI  - A nutritional program to improve outcome of very low birth weight infants.
AB  - BACKGROUND & AIMS: The growth of very low birth weight infants does not match
      intrauterine trajectories, likely due to inappropriate caloric intake. We
      therefore investigated whether modification of the standard nutritional schedule
      can impact postnatal growth. METHODS: We introduced a set of evidence-based
      strategies in a study group of infants (n = 123): 1) higher maximum intake of
      intravenous amino acids and lipids; 2) prioritisation of earlier enteral feeding;
      3) faster attainment of full enteral feeds; 4) daily adjustment of enteral feeds
      according to growth trajectory; and 5) utilisation of an electronic pre
      structured prescription ordering system that tracks individual growth and energy
      intake. These infants were compared with a control group (n = 115) in a pre/post
      retrospective cohort study. RESULTS: The study group achieved a higher caloric
      intake, attained full enteral feeds 5 days earlier, and returned to their birth
      weight more rapidly than the control group. At 36 weeks postmenstrual age,
      infants who had been born at <30 weeks were heavier (Delta260 g) but had a
      similar percentage fat mass. Those born at <28 weeks had a larger head
      circumference (Delta1.4 cm) and lower sepsis rate (7.8%). CONCLUSIONS:
      Optimization of early postnatal nutrition and daily adjustment of milk intake
      according to weight gain improved growth, without any unfavourable outcomes for
      body composition and neurodevelopmental follow-up.

PMID- 21890251
TI  - Effects of high atmospheric CO2 concentration on root hydraulic conductivity of
      conifers depend on species identity and inorganic nitrogen source.
AB  - We examined root hydraulic conductivity (L(p)) responses of one-year-old
      seedlings of four conifers to the combined effects of elevated CO2 and inorganic
      nitrogen (N) sources. We found marked interspecific differences in L(p) responses
      to high CO2 ranging from a 37% increase in P. abies to a 27% decrease in P.
      menziesii, but these effects depended on N source. The results indicate that CO2
      effects on root water transport may be coupled to leaf area responses under
      nitrate (NO(3)(-)), but not ammonium (NH(4)(+)) dominated soils. To our
      knowledge, this is the first study that highlights the role of inorganic N source
      and species identity as critical factors that determine plant hydraulic responses
      to rising atmospheric CO2 levels. The results have important implications for
      understanding root biology in a changing climate and for models designed to
      predict feedbacks between rising atmospheric CO2, N deposition, and ecohydrology.

PMID- 21890252
TI  - Engineered nanomaterials in rivers--exposure scenarios for Switzerland at high
      spatial and temporal resolution.
AB  - Probabilistic material flow analysis and graph theory were combined to calculate
      predicted environmental concentrations (PECs) of engineered nanomaterials (ENMs)
      in Swiss rivers: 543 river sections were used to assess the geographical
      variability of nano-TiO(2), nano-ZnO and nano-Ag, and flow measurements over a 20
      year period at 21 locations served to evaluate temporal variation. A conservative
      scenario assuming no ENM removal and an optimistic scenario covering complete ENM
      transformation/deposition were considered. ENM concentrations varied by a factor
      5 due to uncertain ENM emissions (15%-85% quantiles of ENM emissions) and up to a
      factor of 10 due to temporal river flow variations (15%-85% quantiles of flow).
      The results indicate highly variable local PECs and a location- and time
      dependent risk evaluation. Nano-TiO(2) median PECs ranged from 11 to 1'623 ng L(
      1) (conservative scenario) and from 2 to 1'618 ng L(-1) (optimistic scenario).
      The equivalent values for nano-ZnO and nano-Ag were by factors of 14 and 240
      smaller.

PMID- 21890254
TI  - What should a guideline panel do when evidence is inconclusive? The case of
      treatments for CKD-mineral and bone disorder (CKD-MBD).

PMID- 21890253
TI  - XAFS study of starch-stabilized magnetite nanoparticles and surface speciation of
      arsenate.
AB  - It has been shown that starch can effectively stabilize nanoscale magnetite
      particles, and starch-stabilized magnetite nanoparticles (SMNP) are promising for
      in situ remediation of arsenic-contaminated soils. However, a molecular level
      understanding has been lacking. Here, we carried out XAFS studies to bridge this
      knowledge gap. Fe K-edge XAFS spectra indicated that the Fe-O and Fe-Fe
      coordination numbers of SMNP were lower than those for bare magnetite particles,
      and these coordination numbers decreased with increasing starch concentration.
      The decrease in the average coordination number at elevated stabilizer
      concentration was attributed to the increase in the surface-to-volume ratio.
      Arsenic K-edge XAFS spectra indicated that adsorbed arsenate on SMNP consisted
      primarily of binuclear bidentate (BB) complexes and monodentate mononuclear (MM)
      complexes. More BB complexes (energetically more favorable) were observed at
      higher starch concentrations, indicating that SMNP not only offered greater
      adsorption surface area, but also stronger adsorption affinity toward arsenate.

PMID- 21890255
TI  - Erythropoiesis-stimulating agent responsiveness and mortality in hemodialysis
      patients: results from a cohort study from the dialysis registry in Japan.
AB  - BACKGROUND: Patient responsiveness to erythropoiesis-stimulating agents (ESAs),
      notoriously difficult to measure, has attracted attention for its association
      with mortality. We defined categories of ESA responsiveness and attempted to
      clarify their association with mortality. STUDY DESIGN: Cohort study. SETTING &
      PARTICIPANTS: Data from Japan's dialysis registry (2005-2006), including 95,460
      adult hemodialysis patients who received ESAs. PREDICTOR: We defined 6 categories
      of ESA responsiveness based on a combination of ESA dosage (low [<6,000 U/wk] or
      high [>=6,000 U/wk]) and hemoglobin level (low [<10 g/dL], medium [10-11.9 g/dL],
      or high [>=12 g/dL]), with medium hemoglobin level and low-dose ESA therapy as
      the reference category. OUTCOMES: All-cause and cardiovascular mortality during 1
      year follow-up. MEASUREMENTS: HRs were estimated using a Cox model for the
      association between responsiveness categories and mortality, adjusting for
      potential confounders such as age, sex, postdialysis weight, dialysis duration,
      comorbid conditions, serum albumin level, and transferrin saturation. RESULTS:
      Median ESA dosage (4,500-5,999 U/wk) was used as a cutoff point, and mean
      hemoglobin level was 10.1 g/dL in our cohort. Of 95,460 patients during follow
      up, 7,205 (7.5%) died of all causes, including 5,586 (5.9%) cardiovascular
      deaths. Low hemoglobin levels and high-dose ESA therapy were both associated with
      all-cause mortality (adjusted HRs, 1.18 [95% CI, 1.09-1.27] for low hemoglobin
      level with low-dose ESA and 1.44 [95% CI, 1.34-1.55] for medium hemoglobin level
      with high-dose ESA). Adjusted HRs for high-dose ESA with low hemoglobin level
      (hyporesponsiveness) were 1.94 (95% CI, 1.82-2.07) for all-cause and 2.02 (95%
      CI, 1.88-2.17) for cardiovascular mortality. We also noted the interaction
      between ESA dosage and hemoglobin level on all-cause mortality (likelihood ratio
      test, P = 0.002). LIMITATIONS: Potential residual confounding from unmeasured
      factors and single measurement of predictors. CONCLUSIONS: Mortality can be
      affected by ESA responsiveness, which may include independent and interactive
      effects of ESA dose and hemoglobin level. Responsiveness category has prognostic
      importance and clinical relevance in anemia management.

PMID- 21890256
TI  - Lifetime income patterns and alcohol consumption: investigating the association
      between long- and short-term income trajectories and drinking.
AB  - Lifetime patterns of income may be an important driver of alcohol use. In this
      study, we evaluated the relationship between long-term and short-term measures of
      income and the relative odds of abstaining, drinking lightly-moderately and
      drinking heavily. We used data from the US Panel Study on Income Dynamics (PSID),
      a national population-based cohort that has been followed annually or biannually
      since 1968. We examined 3111 adult respondents aged 30-44 in 1997. Latent class
      growth mixture models with a censored normal distribution were used to estimate
      income trajectories followed by the respondent families from 1968 to 1997, while
      repeated measures multinomial generalized logit models estimated the odds of
      abstinence (no drinks per day) or heavy drinking (at least 3 drinks a day),
      relative to light/moderate drinking (<1-2 drinks a day), in 1999-2003. Lower
      income was associated with higher odds of abstinence and of heavy drinking,
      relative to light/moderate drinking. For example, belonging to a household with
      stable low income ($11-20,000) over 30 years was associated with 1.57 odds of
      abstinence, and 2.14 odds of heavy drinking in adulthood. The association between
      lifetime income patterns and alcohol use decreased in magnitude and became non
      significant once we controlled for past-year income, education and occupation.
      Lifetime income patterns may have an indirect association with alcohol use,
      mediated through current socioeconomic conditions.

PMID- 21890257
TI  - Estimates of peer effects in adolescent smoking across twenty six European
      countries.
AB  - Although it is widely believed that one of the key factors influencing whether an
      adolescent smokes or not is the smoking behaviour of his or her peers, empirical
      evidence on the magnitude of such peer effects, and even on their existence, is
      mixed. This existing evidence comes from a range of studies using a variety of
      country-specific data sources and a variety of identification strategies. This
      paper exploits a rich source of individual level, school-based, survey data on
      adolescent substance use across countries--the 2007 European Schools Survey
      Project on Alcohol and Other Drugs--to provide estimates of peer effects between
      classmates in adolescent smoking for 75,000 individuals across 26 European
      countries, using the same methods in each case. The results suggest statistically
      significant peer effects in almost all cases. These peer effects estimates are
      large: on average across countries, the probability that a 'typical' adolescent
      smokes increases by between .31 and .38 percentage points for a one percentage
      point increase in the proportion of classmates that smoke. Further, estimated
      peer effects in adolescent smoking are stronger intra-gender than inter-gender.
      They also vary across countries: in Belgium, for example, a one percentage point
      increase in reference group smoking is associated with a .16 to .27 percentage
      point increase in own smoking probability; in The Netherlands the corresponding
      increase is between .42 and .59 percentage points.

PMID- 21890259
TI  - Prevalence of maternal anaemia and its predictors: a multi-centre study.
AB  - OBJECTIVE: To investigate the prevalence, predictors, and management of anaemia
      in pregnancy. STUDY DESIGN: A multi centre study across 11 maternity units in the
      UK. Data were collected over a two week study period in 2008 on maternal history,
      haemoglobin (Hb) and ferritin concentrations, iron therapy during pregnancy and
      in the postpartum period. Logistic regression models were used to explore factors
      associated with anaemia during pregnancy. Main outcomes included anaemia, defined
      as Hb<11 g/dl at booking, Hb<10.5 g/dl in subsequent antenatal visits, and Hb<10
      g/dl postnatally. RESULTS: Completed data were received on 2103 of 2155 women
      (97% completion rate). Of these, 24.4% (502) (95% CI 22.5-26.2%) were anaemic at
      some stage during the antenatal period. Predictors for having anaemia by 32 weeks
      gestation included young maternal age (odds ratio 1.96, 95% CI 1.38-2.79), non
      white ethnic origin (odds ratios varied 1.37-2.89 depending on ethnic origin) and
      increasing parity (odds ratio 1.24, 95% CI 1.08-1.41). Of women who had postnatal
      Hb levels checked, 30% (309/1031) were anaemic and, depending on centre, 16% to
      86% of these received iron therapy. CONCLUSION: Anaemia was reported in nearly
      one in four women in the antenatal period, and nearly one in three of the women
      who had a postpartum Hb checked. Despite national guidelines, there was
      considerable variation in administration of iron including low utilisation of
      parenteral iron therapy. Future research needs to focus on the consequences of
      iron deficiency anaemia for maternal and infant health outcomes and effectiveness
      of implementation strategies to reduce anaemia.

PMID- 21890258
TI  - Daily effects of air pollutants and pollen types on asthma and COPD hospital
      emergency visits in the industrial and Mediterranean Spanish city of Cartagena.
AB  - BACKGROUND: Associations found in time-series studies on hospital emergency room
      (ER) visits due to asthma and chronic obstructive pulmonary disease (COPD) with
      single air pollutants show some lack of consistency. The respiratory effects of
      aeroallergens in the air pollution mix are not well established. Non-linear
      relationships of different airborne pollen types with certain respiratory
      diseases have also been described. We aim to study the short-term effects of
      major air pollutants and aeroallergen pollen on asthma and COPD hospital ER
      visits in the industrial and Mediterranean Spanish city of Cartagena during 1995
      1998. METHODS: The association of asthma and COPD to ER visits with mean levels
      of sulphur and nitrogen dioxides (SO(2) and NO(2)), total suspended particles
      (TSP), ozone (O(3)), and the main allergenic airborne pollen types were analysed
      using Poisson regression with Generalised Additive Models, taking into account
      delayed effects and adjusting for long-term trends, seasonality, weather
      conditions, holidays and flu notifications. RESULTS: Multipollutant models showed
      a similar relative risk (RR) increase (in %), of around 5% in asthma and COPD ER
      visits per 10 MUg/m(3) SO(2) increments. The risk of an ER visit for the same
      NO(2) increment was 2.6% for asthma and 3.3% for COPD. Visits to the ER due to
      asthma showed a positive increase with both Urticaceae and Poaceae levels, but
      did not substantially modify the previous percentages. CONCLUSIONS: Air levels of
      SO(2) and NO(2) were associated with a substantial increased risk in ER visits
      due to asthma and COPD. The inclusion of Poaceae and Urticaceae pollen did not
      alter that association.

PMID- 21890260
TI  - Scenario realism and welfare estimates in choice experiments--a non-market
      valuation study on the European water framework directive.
AB  - Using choice experiment data for economic valuation we analyse how disbelief in
      survey information could affect the retrieved welfare estimates. We distinguish
      between two types of survey information to the respondents. The first type of
      information concerns the current environmental status of a water body. This
      information is provided prior to the valuation questions and the corresponding
      beliefs in the provided information are also elicited before valuation. The
      second type of information concerns the proposed improvements in the
      environmental status of the water body. We find that average welfare measures
      differ considerably according to whether respondents who disagree with the status
      quo levels and find proposed scenarios unlikely are included or not.

PMID- 21890261
TI  - Status dystonicus in tardive dystonia successfully treated by bilateral deep
      brain stimulation.

PMID- 21890262
TI  - What are the differences between younger and older patients with symptomatic
      small vessel disease?
AB  - OBJECTIVE: Although typically linked to aging, small vessel disease (SVD) is also
      observed in younger adult patients, with common vascular risk factors (RF). We
      aimed to investigate features of SVD occurrence at an early adult age. PATIENTS
      AND METHODS: Vascular RF, functional and cognitive status and severity of lesions
      on MRI expressed as total score on Age-Related White Matter Changes (ARWMC) scale
      were analyzed in 200 consecutive patients with cerebral SVD admitted to a
      tertiary neurological hospital. Variables were compared between younger (35-55
      years) and older (>56 years) patients. RESULTS: In this study, 63 (31.5%) of
      patients were 55 years or younger. Both age groups had comparable RF profiles,
      but smoking emerged as an independent predictor for SVD at a younger age (OR 2.9;
      95% CI 1.5-5.5; p=0.002). Younger patients had better functional (OR 1.8; 95% CI
      1.3-2.5; p=0.0001) and cognitive (chi(2) 13.94; p=0.0009) status compared to
      older patients. However, two thirds of younger patients had some degree of
      cognitive deficit. Total score on ARWMC scale was lower in younger patients (mean
      12.3 in younger versus 15.2 in older, OR 1.11; 95% CI 1.0-1.18; p=0.001). There
      was a strong correlation in both groups between functional score, cognitive
      status and ARWMC score (p<0.0001). CONCLUSION: In our dataset, younger patients
      with SVD shared common vascular RF with older patients. In the group aged <=55,
      better functional and cognitive status and less severe MRI changes were noted.
      However, a substantial number of younger SVD patients presenting with TIA or
      ischemic stroke had various deficits.

PMID- 21890263
TI  - Ulnar nerve compression in the cubital tunnel by a nodular fasciitis.

PMID- 21890264
TI  - Rapid automated detection of ABL kinase domain mutations in imatinib-resistant
      patients.
AB  - ABL tyrosine kinase inhibitor (TKI), imatinib is used for BCR-ABL(+) leukemias.
      We developed an automatic method utilizing guanine-quenching probes (QP) to
      detect 17 kinds of mutations frequently observed in imatinib-resistance. Results
      were obtained from 100MUL of whole blood within 90min by this method. Detected
      mutations were almost identical between QP method and direct sequencing.
      Furthermore, the mutation-biased PCR (MBP) was added to the QP method to increase
      sensitivity, resulting earlier detection of T315I mutation which was insensitive
      to any ABL TKIs. Thus, the QP and MBP-QP may become useful methods for the
      management of ABL TKI-treated patients.

PMID- 21890265
TI  - Pro-inflammatory and tumour proliferative properties of excess visceral adipose
      tissue.
AB  - Obesity has been associated with increased incidence and mortality of oesophageal
      and colorectal adenocarcinoma. Excess central adiposity may drive this
      association through an altered inflammatory milieu. Utilising a unique adipose
      tissue bioresource we aimed to determine the pro-tumour properties of visceral
      adipose tissue. Comparing subcutaneous and visceral adipose tissue depots, we
      observed significantly higher levels of VEGF and IL-6, along with significantly
      higher proportions of CD8(+) T cells and NKT cells in visceral adipose tissue.
      Significantly higher levels of VEGF were observed in the conditioned media from
      visceral adipose tissue of centrally obese compared to non-obese patients. We
      also report a significant increase in oesophageal and colorectal tumour cell
      proliferation following culture with conditioned media from visceral adipose
      tissue of centrally obese patients. Neutralising VEGF in the conditioned media
      significantly decreased tumour cell proliferation. This novel report highlights a
      potential mechanism whereby visceral adipose tissue from centrally obese cancer
      patients may drive tumour progression.

PMID- 21890266
TI  - Feasibility study of a photocatalytic reactor for in situ groundwater remediation
      of organic compounds.
AB  - Remediation of groundwater contaminated by gasoline leakage from underground
      structures is usually complicated and costly. This work describes the use of an
      underground reactor, in a sand tank, placed downgradient from a simulated leakage
      of MTBE and other gasoline components. The reactor, Honeycomb I, is full scale in
      the horizontal plane. It tested the remediation of MTBE plumes at various
      velocities and in the presence of other gasoline compounds (toluene, ethylbenzene
      and o-xylene - TEo-X). The overall performance of Honeycomb I was evaluated and
      the efficiencies of two different experimental scales were compared. The MTBE
      plume was longer but narrower with increasing groundwater to MTBE velocity ratio.
      MTBE appeared to have a minor co-solvent effect on the TEo-X migration as TEo-X
      migrated at the MTBE migration rate but at significantly low concentrations. The
      MTBE removal efficiency decreased by about 8% in the presence of TEo-X. The
      scaled up Honeycomb I successfully treated 212L of groundwater in 24 days and
      demonstrated its reliability over a 10-month period, achieving an overall 76%
      MTBE removal. In essence, this study demonstrated the potential of the
      immobilised photocatalytic reactor for in situ groundwater remediation, at the
      velocities tested in this study.

PMID- 21890267
TI  - Potential of modified iron-rich foundry waste for environmental applications:
      Fenton reaction and Cr(VI) reduction.
AB  - A magnetic fraction (15%) from a waste of foundry sand (WFS), composed of sand,
      carbon, bentonite clay and iron (10%) was modified by thermal treatment at 400,
      600 and 800 degrees C under inert atmosphere. Mossbauer analyses showed that the
      thermal treatment increased the amount of Fe(3)O(4) from 25 to 55% by reduction
      of Fe(2)O(3) and highly dispersed Fe(3+) by the carbon present in the waste. The
      Fe(3)O(4) caused a significant increase on the activity of two important
      reactions with application in environmental remediation: the Fenton oxidation of
      indigo carmine dye with H(2)O(2) and the reduction of Cr(VI) to Cr(III). The
      magnetic fraction of WFS was also mixed with hematite (Fe(2)O(3)) and thermally
      treated at 400, 600 and 800 degrees C. This treatment produced large amounts of
      surface Fe(3)O(4) and increased substantially the rate of Fenton reaction as well
      as Cr(VI) reduction. This reactivity combined with the presence of carbon (an
      adsorbent for organic contaminants), bentonite clay (an adsorbent for metallic
      contaminants) and the granulometry/packing/hydrodynamic features make WFS a
      promising material for use in reactive permeable barriers.

PMID- 21890268
TI  - Performance and mechanisms of a microbial-earthworm ecofilter for removing
      organic matter and nitrogen from synthetic domestic wastewater.
AB  - The performance of a microbial-earthworm ecofilter for the treatment of synthetic
      domestic wastewater is evaluated, and the mechanisms of organic matter and
      nitrogen transformation investigated. Vermifiltration efficiently reduced
      chemical oxygen demand (COD) and ammonia nitrogen (NH(3)-N) from the influent. A
      combination of soil with sawdust possessed higher porosity and specific surface
      area than other media, and this microporous structure together with wormcast
      surface greatly facilitated COD reduction at depths from 5 to 35 cm. Nitrogen
      variations in wastewater were influenced by soil properties, earthworm
      activities, and wormcast characteristics. Their interaction with added nitrogen
      determined soil nitrogen distribution. In addition, denaturing gradient gel
      electrophoresis (DGGE) profiles revealed a highly diverse community of ammonia
      oxidizing bacteria (AOB) and Nitrospira in soil layers. There was a positive
      correlation between the Shannon biodiversity index for AOB and decreasing NH(3)-N
      concentration, indicating that dominant soil microbes played a major role in
      removing NH(3)-N and nitrogen conversion. In contrast to previous reports,
      identification of retrieved sequences of AOB species showed that most belonged to
      an uncertain AOB genus. This biofiltration system is a low cost, efficient
      alternative for decontaminating local domestic wastewater.

PMID- 21890269
TI  - Removal of Chemazol Reactive Red 195 from aqueous solution by dehydrated beet
      pulp carbon.
AB  - An agricultural low-cost by-product, dehydrated beet pulp carbon (DBPC) was used
      as an adsorbent for removal of Chemazol Reactive Red 195 (CRR 195) from aqueous
      solution. The surface area of DBPC was measured as 9.5m(2)g(-1) by using BET
      method. The results indicated that adsorption was strongly pH-dependent and
      optimum pH was determined as 1.0. The maximum dye adsorption capacity was
      obtained as 58.0 mg g(-1)at the temperature of 50 degrees C at this pH value. The
      Freundlich and Langmuir adsorption models were used for the mathematical
      description of the adsorption equilibrium and it was reported that, experimental
      data fitted very well to Freundlich model. Mass transfer and kinetic models were
      applied to the experimental data to examine the mechanisms of adsorption and
      potential rate-controlling steps. It was found that both external mass transfer
      and intra-particle diffusion played an important role in the adsorption
      mechanisms of dye and adsorption kinetics followed the pseudo-first-order type
      kinetic model. The thermodynamic parameters such as, Gibbs free energy changes
      (DeltaG degrees ), standard enthalpy change (DeltaH degrees ) and standard
      entropy change (DeltaS degrees ) had been determined. The results show that
      adsorption of CRR 195 on DBPC is endothermic and spontaneous in nature.

PMID- 21890270
TI  - Critical assessment of suitable methods used for determination of antibacterial
      properties at photocatalytic surfaces.
AB  - This work describes the development of methods necessary for antibacterial effect
      evaluation on irradiated TiO(2) layers. Two methods using bacteria suspensions
      and the glass adhesion method (based on ISO 27447:2009(E)) were critically
      assessed and compared. As test bacteria gram negative Escherichia coli and gram
      positive Enterococcus faecalis were employed. The method using 50 cm(3) of
      bacteria suspension is convenient for testing layers with strong antibacterial
      effect (prepared from powder photocatalysts). For the evaluation of the
      antibacterial effect of sol gel layers, the glass adhesion method based on the
      ISO is more appropriate than the method with 3 cm(3) of bacteria suspension. The
      reason is that the later does not allow a distinction between the inhibition
      effect of TiO(2) and UV light itself. Some improvements of the ISO method were
      suggested, namely the use of gelatinous pills (CCM) of bacteria, using saline
      solution instead of nutrient broth for bacteria suspension preparation and the
      application of selective media for bacteria cultivation. Decreasing the light
      intensity from 0.6 mW cm(-2) to 0.2 mW cm(-2) (fulfilling the requirements of the
      ISO) results in almost negligible effect of UV light itself, thus enabling proper
      testing of the antibacterial properties of TiO(2) thin films.

PMID- 21890271
TI  - Assessment of heavy metal contamination in sediments of the Tigris River (Turkey)
      using pollution indices and multivariate statistical techniques.
AB  - Heavy metal concentrations in sediment samples from the Tigris River were
      determined to evaluate the level of contamination. The highest concentrations of
      metals were found at the first site due to metallic wastewater discharges from
      copper mine plant. Sediment pollution assessment was carried out using
      contamination factor (CF), pollution load index (PLI), geoaccumulation index
      (Igeo) and enrichment factor (EF). The CF values for Co, Cu and Zn were >6 in
      sediments of the first site, which denotes a very high contamination by these
      metals. The PLIs indicated that all sites except the first site were moderately
      polluted. Cu, Co, Zn and Pb had the highest Igeo values, respectively. The mean
      EF values for all metals studied except Cr and Mn were >1.5 in the sediments of
      the Tigris River, suggesting anthropogenic impact on the metal levels in the
      river. The concentrations of Cr, Cu, Ni and Pb are likely to result in harmful
      effects on sediment-dwelling organisms which are expected to occur frequently
      based on the comparison with sediment quality guidelines. PCA/FA and cluster
      analysis suggest that As, Cd, Co, Cr, Cu, Mn, Ni and Zn are derived from the
      anthropogenic sources, particularly metallic discharges of the copper mine plant.

PMID- 21890272
TI  - Applying the Triad method in a risk assessment of a former surface treatment and
      metal industry site.
AB  - With a greater focus on soil protection in the E.U., the need for ecological risk
      assessment tools for cost-effective characterization of site contamination is
      increasing. One of the challenges in assessing the risk of soil contaminants is
      to accurately account for changes in mobility of contaminants over time, as a
      result of ageing. Improved tools for measuring the bioavailable and mobile
      fraction of contaminants is therefore highly desirable. In this study the Triad
      method was used to perform a risk characterization of a former surface treatment
      and metal industry in Eskilstuna, Sweden. The risk assessment confirmed the
      environmental risk of the most heavily contaminated sample and showed that the
      toxic effect was most likely caused by high metal concentrations. The assessment
      of the two soil samples with low to moderate metal contamination levels was more
      complex, as there was a higher deviation between the results from the three lines
      of evidence; chemistry, (eco)toxicology and ecology. For the slightly less
      contaminated sample of the two, a weighting of the results from the
      ecotoxicological LoE would be recommended in order to accurately determine the
      risk of the metal contamination at the sampling site as the toxic effect detected
      in the Microtox(r) test and OstracodtoxkitTM test was more likely to be due to
      oil contamination. The soil sample with higher total metal concentrations
      requires further ecotoxicological testing, as the integrated risk value indicated
      an environmental risk from metal contamination. The applied methodology, the
      Triad method, is considered appropriate for conducting improved environmental
      risk assessments in order to achieve sustainable remediation processes.

PMID- 21890273
TI  - Implication of allopregnanolone in the antinociceptive effect of N
      palmitoylethanolamide in acute or persistent pain.
AB  - We investigated the involvement of de novo neurosteroid synthesis in the
      mechanisms underlying the analgesic and antihyperalgesic effects of N
      palmitoylethanolamine (PEA) in two models of acute and persistent pain, the
      formalin test and carrageenan-induced paw edema. The pivotal role of peroxisome
      proliferator-activated receptor (PPAR)-alpha in the antinocifensive effect of PEA
      was confirmed by the lack of this effect in PPAR-alpha-null mice. PEA
      antinociceptive activity was partially reduced when the animals were treated with
      aminoglutethimide or finasteride, implying that de novo neurosteroid synthesis is
      involved in the effect of PEA. Accordingly, in the spinal cord, the
      allopregnanolone (ALLO) levels were increased by PEA treatment both in formalin-
      and carrageenan-exposed mice, as revealed by gas chromatography-mass
      spectrometry. In agreement with those data, in both pain models, PEA
      administration in challenged mice specifically restored the expression of two
      proteins involved in neurosteroidogenensis, the steroidogenic acute regulatory
      protein (StAR) and cytochrome P450 side-chain cleavage (P450scc) in the
      ipsilateral horns of spinal cord, without affecting their expression in the
      contralateral side. These results provide new information about the involvement
      of de novo neurosteroid synthesis in the modulation of pain behavior by PEA.

PMID- 21890274
TI  - Anthelmintic activity of Jatropha curcas L. seeds on Haemonchus contortus.
AB  - The aim of this study was to evaluate the anthelmintic activity of hexane (HE),
      ethyl acetate (EA) and ethanol (EE) extracts obtained from the seeds of Jatropha
      curcas using the egg hatch inhibition assay (EHA) and the artificial larval
      exsheathment inhibition assay (LEIA). For the egg hatch assay, HE, EA and EE were
      used in concentrations of 3.12, 6.25, 12.5, 25 and 50 mg ml(-1), accompanied by a
      negative control (5% Tween 80) and a positive control (0.025 g ml(-1)
      thiabendazole). In LEIA, the extracts were tested at a concentration of 1000 MUg
      ml(-1), accompanied by a negative control (PBS). To evaluate the effect of
      tannins, the extract with the greatest effect was incubated with polyvinyl
      polypyrrolidone (PVPP). The EE (50 mg ml(-1)) inhibited 99.8% of egg hatching.
      After the addition of PVPP, the ovicidal effectiveness of EE was reduced to
      91.9%. Using the HE and EA, inhibition of egg hatching was 15.3% and 32.2%,
      respectively. In the LEIA, 18.9% of L3 incubated with EE were exsheathed
      (p<0.01). The addition of PVPP to EE reversed the inhibitory effect on larval
      exsheathment. The percentage of exsheathment of L3 incubated with HE (99.6%) and
      EA (97.8%) did not differ from the control group (p>0.05). The results show that
      the effects of EE on eggs are not solely due to the tannins. However, these
      secondary metabolites are implicated in blocking the larval exsheathment.

PMID- 21890275
TI  - Prevalence of Giardia and Cryptosporidium species in dog park attending dogs
      compared to non-dog park attending dogs in one region of Colorado.
AB  - Dog parks are very popular in urban areas, but there are no current studies
      attempting to correlate visits to dog parks and risk of colonization by enteric
      parasites. The purpose of this study was to determine whether dog park visitation
      is associated with an increased prevalence of enteric parasites or an increase in
      prevalence of gastrointestinal signs in dogs in northern Colorado. Feces from
      dogs owned by veterinary students or Veterinary Teaching Hospital staff members
      were submitted with a completed survey form detailing dog park attendance rates,
      fecal character scores, and other clinical information. Feces were examined
      microscopically for parasites after sugar centrifugation, for Giardia spp. cysts
      and Cryptosporidium spp. oocysts by a commercially available immunofluorescence
      assay (FA) and the FA positive samples were genotyped after PCR amplification.
      The Giardia assemblages were determined using the glutamate dehydrogenase (GDH)
      beta-giardin and triose phosphate isomerase (TPI) genes and the Cryptosporidium
      species were determined using the heat shock protein-70 gene. A total of 129
      fecal samples were assayed; 66 were from dog park attending dogs and 63 were from
      non-dog park-attending dogs. The overall parasite prevalence rate was 7.0% (9 of
      129 samples). Dog park attending dogs were more likely to be positive for Giardia
      or Cryptosporidium than non-dog park-attending dogs (p=0.0279), but there was no
      association of gastrointestinal signs with dog park attendance or with fecal
      flotation or FA results. The five Giardia isolates were assemblage C and/or D and
      the one Cryptosporidium isolate was Ctenocephalides canis.

PMID- 21890276
TI  - Vaccination of rabbits against coccidiosis using precocious lines of Eimeria
      magna and Eimeria media in Benin.
AB  - Three groups of twelve 35-day-old rabbits were used for the experiment. Two
      groups were vaccinated with a mixture of precocious lines of Eimeria magna and
      Eimeria media originating from corresponding wild strains isolated in Benin. One
      group benefited of a booster whereas the second one was kept without booster. A
      third non-vaccinated group was used as control. All groups were challenged per os
      with an equal mixture of the wild strains of E. magna and E. media at a dose of
      104 oocysts per animal. Three weeks after the challenge inoculation, no case of
      diarrhoea was recorded in the two groups of vaccinated rabbits, as compared to
      the non-vaccinated rabbits that developed diarrhoea. No mortality was recorded in
      the three groups. During the patent period, oocyst output of vaccinated rabbits
      was significantly lower than that of control animals (P<0.01), confirming a good
      immunogenic characteristic of the precocious lines. No booster effect was noticed
      for the boost vaccinated group. The daily weigh gain of the two groups of
      vaccinated rabbits was significantly higher than that of the non-vaccinated
      rabbits (P<0.05). Consequently the precocious lines of Benin origin turned out to
      be immunogenic and therefore constitute good potential candidates for vaccine
      production for this country.

PMID- 21890278
TI  - Degenerative pathological irritations to cervical PLL may play a role in
      presenting sympathetic symptoms.
AB  - The mechanism of cervical vertigo remains unknown. Stimulation of arterial
      vertebralis caused by osteophyte of the Luschka joint or segmental instability of
      the cervical spine was considered to be a potential factor contributing to it.
      Years of studies found that the ischemia of the vertebral artery is not directly
      correlated with the clinical symptoms of vertigo, and can not be used to explain
      cervical vertigo as a sole reason. As proven by clinical practical experience,
      the routine anterior cervical decompression and fusion (ACDF) procedure, in which
      the degenerative disc and posterior longitudinal ligament (PLL) were often
      removed, shows positive results for elimination of the sympathetic symptoms. In
      this article, we hypothesize that: (1) there are sympathetic nerve postganglionic
      fibers distributed in the PLL or discs; (2) pathological changes secondary to
      degeneration of the intervertebral disc may cause irritation of sympathetic nerve
      fibers in PLL or discs, leading to sympathetic symptoms via certain pathways; (3)
      removal of the PLL or stabilization of the segment which decreases the irritation
      to PLL will help to eliminate the sympathetic symptoms.

PMID- 21890280
TI  - Altered metabolism of maternal micronutrients and omega 3 fatty acids
      epigenetically regulate matrix metalloproteinases in preterm pregnancy: a novel
      hypothesis.
AB  - Preterm birth is an important perinatal health problem. Several possible
      mechanisms have been proposed but it may be important to have a testable
      mechanistic hypothesis that can explain the possible common mechanism for preterm
      births around the globe. Altered metabolism of micronutrients, like folic acid,
      vitamin B(12), zinc and copper are known to be associated with adverse pregnancy
      outcomes such as preterm birth. We have recently reported that increased
      oxidative stress and reduced docosahexaenoic acid levels are associated with
      preterm delivery. Matrix metalloproteinases and their tissue inhibitors play
      vital roles in extracellular matrix remodelling/degradation during pregnancy.
      Expression and the activity of matrix metalloproteinases have been shown to be
      regulated by oxidative stress and hyperhomocysteinemia. We have recently reported
      gestation dependant changes in placental global methylation levels. Here, we
      propose a novel hypothesis that altered maternal micronutrients (folic acid,
      vitamin B(12)), omega 3 fatty acids, and consequent oxidative stress lead to
      altered epigenetic mechanisms resulting in altered expression of matrix
      metalloproteinases and their tissue inhibitors during pregnancy. This may have
      important implications in the epigenetic programming of adult diseases since
      preterm infants are known to be at increased risk for neurodevelopmental,
      metabolic and cardiovascular dysfunctions in later life.

PMID- 21890277
TI  - A history of depression in women is associated with an altered GABAergic
      neuroactive steroid profile.
AB  - The 3alpha,5alpha- and 3alpha,5beta-reduced metabolites of progesterone,
      deoxycorticosterone, and dehydroepiandrosterone (DHEA) have potent effects on
      neurotransmission mediated by GABA(A) receptors, and dysregulation of these
      receptors has been implicated in depression. Using gas chromatography-mass
      spectrometry, we compared neuroactive steroid concentrations in women with a
      history of depressive disorders, but who were in full remission at the time of
      testing (n=11) to never depressed women (n=17) both before and after a challenge
      with oral micronized progesterone (300 mg). Serum concentrations of the following
      were obtained: four progesterone-derived GABAergic neuroactive steroids, the
      precursor pregnenolone, androstenedione-derived neuroactive steroids, and the
      precursor DHEA. As an index of conversion of progesterone to neuroactive
      steroids, we also examined ratios of neuroactive steroids to progesterone
      following the oral progesterone challenge. Results indicated that both before and
      after oral progesterone, women with histories of depression showed lower
      concentrations of all GABAergic neuroactive steroids than never depressed women.
      Those with a history of depression also had lower cortisol concentrations.
      Because serum neuroactive steroids are mainly synthesized in the adrenals, we
      hypothesize that histories of depression may be associated with persistent
      adrenal suppression. Following the progesterone challenge, ratios of the
      progesterone-derived neuroactive steroids to plasma progesterone concentrations
      were elevated in women with depression histories, suggesting there may be an
      adaptive shift in the metabolism of progesterone that compensates for lower
      circulating neuroactive steroid concentrations.

PMID- 21890279
TI  - Correlation of endothelin-1 mRNA expression and bone structure in advanced
      osteoarthritis.
AB  - Recent understandings of the vascular contribution of pathophysiology of
      osteoarthritis (OA) mount new evidence of cross-talking between subchondral bone
      tissue and articular cartilage that might have a decisive role in a
      pathophysiology of Osteoarthritis (OA). These understandings include blood flow
      (or interstitial fluid) impairment in subchondral bone. With regard to the
      mentioned role of the vasculature, the absence of custom nourishing to articular
      cartilage, and established, vasoconstrictive role of endothelin-1 (ET-1) it was
      reasonable to assume that ET-1 has an inconvertible role in pathophysiology of
      OA. Another moment in pathophysiology of OA is apoptosis of subchondral
      osteocytes, what induces osteoclastic resorption and at least temporarily reduces
      the bony support for the overlying cartilage. Since regional dependence of this
      protein's expression was presumed, we suggest a regional division of subchondral
      bone by histomorphometrical analysis and quantification of identified protein by
      Real Time Polymerase Chain Reaction Analysis (RT-PCR). Obtained results should be
      compared to serum levels of soluble ET-1, what would enforce this methods
      validity. Herewith, a new screening marker of patients with osteoarthritis would
      be established. This would enable detection and follow-up of groups threatened by
      this, growing, cause of disability and decreased quality of life.

PMID- 21890281
TI  - Effects of different storage conditions on quality related porphyrin fluorescence
      signatures of pork slices.
AB  - This study evaluated the potential of fluorescence as an indicator of pork
      quality by determining the effects of various conditions on fluorescence
      signatures (excitation at 420 nm, emission at 550-750 nm). Storage of porcine
      musculus longissimus dorsi in PE bags led to a clear increase in porphyrin
      fluorescence intensity after approx. 10 d post mortem. Modified gas atmosphere
      (70% O(2), 30% CO(2)) inhibited the fluorescence emission of zinc protoporphyrin
      and protoporphyrin IX due to quenching by oxygen. Bleaching processes caused
      similar effects by halogen light exposure during meat storage. However, already
      formed signals could not be manipulated by oxygen or halogen light. Storage under
      vacuum reduced the quenching effects and resulted in increased fluorescence
      intensities. Freezing and thawing of meat samples delayed and reduced the
      increase in fluorescence intensity. Only minor effects could be detected at long
      term frozen storage for two months. Consequently porphyrin fluorescence analysis
      is a potential means to indicate changes of pork quality and remaining shelf
      life.

PMID- 21890282
TI  - The Obsessive Compulsive Cocaine Use Scale: development and initial validation of
      a self-rated instrument for the quantification of thoughts about cocaine use.
AB  - BACKGROUND: Craving is a hallmark of addiction and characterized by obsessive
      thoughts about, and compulsive urges to use, a substance. While craving is
      frequently thought of as primarily being a feature of acute withdrawal, there is
      evidence to suggest that it increases in strength over extended periods of
      abstinence. While several measures are available to assess acute craving states,
      there remains a lack of clinical measures appropriate for capturing the enduring
      cognitive aspects of urges to use drugs. The present study was designed to
      develop and validate a measure of obsessive-compulsive thoughts in cocaine
      dependent individuals. METHODS: The proposed 14-item Obsessive Compulsive Cocaine
      Use Scale (OCCUS) was administered to 107 individuals: 55 participants meeting
      diagnostic criteria for cocaine dependence and 52 recreational users of cocaine.
      In addition to the OCCUS, participants also completed the Drug Abuse Screening
      Test, Cocaine Craving Questionnaire-Now, and Social Desirability Scale of the
      California Personality Inventory. RESULTS: Results of confirmatory factor
      analysis indicated that the OCCUS fit the two-factor structure of the Obsessive
      Compulsive Drinking Scale on which it was based, independently assessing the
      "obsessive" and "compulsive" aspects of cocaine dependence. The OCCUS
      demonstrated good internal consistency reliability and convergent, discriminant,
      and criterion validity. CONCLUSION: The proposed measure is a promising step
      towards the successful capture of the long-term cognitive features of craving for
      cocaine via self-report, and should represent a useful tool for clinical and
      research use.

PMID- 21890283
TI  - Characterization of bovine ruminal epithelial bacterial communities using 16S
      rRNA sequencing, PCR-DGGE, and qRT-PCR analysis.
AB  - Currently, knowledge regarding the ecology and function of bacteria attached to
      the epithelial tissue of the rumen wall is limited. In this study, the diversity
      of the bacterial community attached to the rumen epithelial tissue was compared
      to the rumen content bacterial community using 16S rRNA gene sequencing, PCR
      DGGE, and qRT-PCR analysis. Sequence analysis of 2785 randomly selected clones
      from six 16S rDNA (~1.4kb) libraries showed that the community structures of
      three rumen content libraries clustered together and were separated from the
      rumen tissue libraries. The diversity index of each library revealed that ruminal
      content bacterial communities (4.12/4.42/4.88) were higher than ruminal tissue
      communities (2.90/2.73/3.23), based on 97% similarity. The phylum Firmicutes was
      predominant in the ruminal tissue communities, while the phylum Bacteroidetes was
      predominant in the ruminal content communities. The phyla Fibrobacteres,
      Planctomycetes, and Verrucomicrobia were only detected in the ruminal content
      communities. PCR-DGGE analysis of the bacterial profiles of the rumen content and
      ruminal epithelial tissue samples from 22 steers further confirmed that there is
      a distinct bacterial community that inhibits the rumen epithelium. The
      distinctive epimural bacterial communities suggest that Firmicutes, together with
      other epithelial-specific species, may have additional functions other than food
      digestion.

PMID- 21890284
TI  - Evaluation of the sensitivity and specificity of bovine tuberculosis diagnostic
      tests in naturally infected cattle herds using a Bayesian approach.
AB  - Test-and-slaughter strategies have been the basis of bovine tuberculosis (BT)
      eradication programs worldwide; however, eradication efforts have not succeeded
      in certain regions, and imperfect sensitivity and specificity of applied
      diagnostic techniques have been deemed as one of the possible causes for such
      failure. Evaluation of tuberculosis diagnostic tools has been impaired by the
      lack of an adequate gold standard to define positive and negative individuals.
      Here, a Bayesian approach was formulated to estimate for the first time
      sensitivity (Se) and specificity (Sp) of the tests [single intradermal tuberculin
      (SIT) test, and interferon-gamma (IFN-gamma) assay] currently used in Spain.
      Field data from the first implementation of IFN-gamma assay (used in parallel
      with SIT test 2-6months after a first disclosure SIT test) in infected beef,
      dairy and bullfighting cattle herds from the region of Castilla and Leon were
      used for the analysis. Model results suggested that in the described situation:
      (i) Se of SIT test was highly variable (40.1-92.2% for severe interpretation,
      median=66-69%), and its Sp was high (>99%) regardless interpretation criteria;
      (ii) IFN-gamma assay showed a high Se (median=89-90% and 83.5% for 0.05 and 0.1
      cut-off points respectively) and an acceptable Sp (85.7% and 90.3% for 0.05 and
      0.1 thresholds) and (iii) parallel application of both tests maximized the
      combined Se (95.6% using severe SIT and 0.05 cut-off point in the IFN-gamma
      assay). These results support the potential use of the IFN-gamma assay as an
      ancillary technique for routine BT diagnosis.

PMID- 21890285
TI  - Multiplex real-time PCR SYBR Green for detection and typing of group III
      Clostridium botulinum.
AB  - Clostridium botulinum type C and type D belonging to the group III organisms, are
      mainly responsible for animal botulism outbreaks. Clinical signs alone are often
      insufficient to make a diagnosis of botulism and a laboratory confirmation is
      required. Laboratory confirmation can be performed by demonstrating the presence
      of botulinum neurotoxins in serum, gastrointestinal contents, liver, wound of
      sick or dead animals, or by demonstrating the presence of C. botulinum in
      gastrointestinal contents, liver, and wound. Demonstration of spores in
      gastrointestinal contents or tissue of animals with clinical signs indicative of
      botulism reinforces the clinical diagnosis. With the aim of detecting and typing
      C. botulinum group III organisms, a multiplex real-time PCR SYBR Green was
      developed and in-house validated. Selectivity, limit of detection, relative
      accuracy, relative specificity, relative sensitivity, and repeatability of the
      method were investigated. The multiplex real-time PCR SYBR green used showed a
      100% selectivity, 100% relative accuracy, 100% relative specificity, 100%
      relative sensitivity and a limit of detection of 277 and 580 DNA copies for C.
      botulinum type C and C. botulinum type D, respectively. The method reported here
      represents a suitable tool for laboratory diagnosis of type C and D botulism and
      for testing a large number of samples collected during the animal botulism
      surveillance and prevention activities.

PMID- 21890286
TI  - Evaluation of salt concentrations, chromogenic media and anatomical sampling
      sites for detection of methicillin-resistant Staphylococcus aureus in pigs.
AB  - The performance of chromogenic media for the detection of methicillin-resistant
      Staphylococcus aureus (MRSA) in humans, has been evaluated in numerous studies.
      However, few comparative studies have been performed for the detection of MRSA in
      pigs. In this study two different salt concentrations (2.5% or 7.5% NaCl) were
      evaluated in the enrichment nutrient broth and three selective chromogenic media
      (chromID MRSA, BrillianceMRSA and MRSASelect) for their ability to detect MRSA in
      swabs from 29 pigs obtained from three different anatomical sampling sites
      (anterior nares, skin behind both ears and perineum). ChromID MRSA showed the
      highest relative sensitivity and specificity after enrichment in 7.5% NaCl,
      followed by MRSASelect and BrilianceMRSA. For all chromogenic media more MRSA
      positive results were obtained for specimens collected from skin behind the ears
      than for specimens taken from both nares and perineum. The results with regard to
      the anatomical sampling sites were confirmed in a larger study on three different
      pig farms involving 60 pigs per farm. Skin behind the ears was the anatomical
      site with the highest relative sensitivity (91.4%) for MRSA detection compared to
      perineum and anterior nares, with a relative sensitivity of 76.5% and 75.3%,
      respectively. An increased relative sensitivity could be achieved when combining
      two anatomical sites. Sampling of anterior nares and skin behind the ears
      appeared to be the most sensitive combination with a relative sensitivity of
      98.2%. These results show that sampling of only the anterior nares underestimates
      the real pig MRSA prevalence.

PMID- 21890288
TI  - Gestational diabetes and preeclampsia--similar risk factor profiles?
AB  - BACKGROUND: Gestational diabetes and preeclampsia are leading causes of
      complications during pregnancy. AIMS: The aims of this study were to quantify the
      probability that both diseases occur together, to evaluate commonality of risk
      factor profiles, and to clarify the connection between gestational diabetes and
      preeclampsia in combination with the maternal body mass index. STUDY DESIGN: We
      analysed data of the German Perinatal Quality Registry 2006, an annual full
      inventory of all hospital births in Germany. SUBJECTS: The Registry contains the
      complete national birth cohort of 668,085 newborn infants and 647,392 mothers
      from 896 German obstetric clinics. OUTCOME MEASURES: Each case of gestational
      diabetes or preeclampsia that was identified during pregnancy by a gynaecologist
      or in the hospital was fully registered. RESULTS: The prevalence of GDM was 2.32%
      and that of PE was 2.31%, resulting in 0.09% of all pregnant women being
      diagnosed with both diseases. GDM was found to be an independent risk factor for
      PE. Increased maternal age, nulliparity, and multiple gestation pregnancies could
      be identified as common risk factors for both diseases, while increased pre
      pregnancy body mass index was found to be the most important predictor for both
      diseases. CONCLUSIONS: As PE and GDM share similar risk factors, identification
      of high-risk groups by simultaneous screening methods seems to be reasonable for
      prevention of complications. Further studies will be needed to investigate
      possible pathophysiological pathways increased body mass index has on the
      induction of both diseases.

PMID- 21890287
TI  - Production and characterization of recombinant transmembrane proteins from
      Mycoplasma hyopneumoniae.
AB  - Mycoplasma hyopneumoniae is the etiological agent of swine enzootic pneumonia
      (EP), a chronic respiratory disease which causes significant economic losses to
      the swine industry worldwide. More efficient strategies for controlling this
      disease are necessary. In this study, we cloned17 genes coding for transmembrane
      proteins from M. hyopneumoniae, among which six were successfully expressed in
      Escherichia coli and had their immunogenic and antigenic properties evaluated.
      All proteins were immunogenic in mice and sera from naturally infected pigs
      reacted with the recombinant proteins, suggesting that they are expressed during
      infection. These antigens may contribute for the development of new recombinant
      vaccines and diagnostic tests against EP.

PMID- 21890289
TI  - Maternal use of selective serotonin reuptake inhibitors during pregnancy and
      neonatal bone density.
AB  - BACKGROUND: Selective serotonin reuptake inhibitors (SSRI) are commonly used to
      treat depression in pregnant women. Several adverse effects of prenatal SSRI
      exposure on the offspring have been described, including decreased growth. SSRI
      use by adults decreases bone mineral density, but this effect had not been
      examined in infants. AIM: To examine growth parameters and bone mineral density
      of infants born to mothers using SSRIs during pregnancy. STUDY DESIGN:
      Anthropometric variables and bone density were compared between 40 newborns
      exposed to SSRIs in utero, and 40 gestational-age matched control infants. Tibial
      bone speed of sound, a marker of bone density and strength, was measured using
      quantitative ultrasound. The difference in bone speed of sound between the two
      groups was compared using linear models, adjusting for relevant confounders.
      RESULTS: Infants in the SSRI-exposed group were shorter, with a marginal
      statistical significance (49.3+/-2.1 vs. 50.1+/-1.3cm, p=0.07), while mean birth
      weight did not differ substantially between study groups. Head circumference was
      significantly smaller in the SSRI group (33.8+/-1.2 vs 34.4+/-1.1cm, p=0.005),
      remaining so even after adjustment for several confounders. No considerable
      difference was found in the bone speed of sound between SSRI-exposed infants and
      controls (3011+/-116 vs. 3029+/-129m/s). CONCLUSIONS: We found no evidence that
      prenatal SSRI exposure hindered neonatal bone quality, yet a marginally shorter
      length and a smaller head circumference raise the possibility of an effect on
      bone growth. We conclude that the effect of SSRIs on fetal bone density seems
      minimal or absent.

PMID- 21890290
TI  - Cryopreservation and fertility of ejaculated and epididymal stallion sperm.
AB  - The cryopreservation of epididymal sperm is important to preserve genetic
      material from valuable deceased males. This study evaluated the viability of
      sperm samples from eight stallions under three conditions: (1) collected using an
      artificial vagina (EJ-0h), (2) recovered from the epididymal cauda immediately
      after orchiectomy (EP-0h), and (3) recovered from the epididymal cauda after 24h
      of storage at 5 degrees C (EP-24h). To obtain EJ-0h sperm, two ejaculates were
      collected from each stallion. After 1 week, the stallions were submitted to
      bilateral orchiectomy, and one of the removed epididymides was flushed to obtain
      EP-0h sperm. The contralateral epididymis was stored at 5 degrees C for 24h
      before being flushed to obtain EP-24h sperm. The sperm samples were analyzed at
      three different times: immediately after sperm recovery, after dilution in the
      freezing extender, and post-thawing. A fertility trial was performed using 39
      estrous cycles. After ovulation induction with 1mg of deslorelin acetate (i.m.),
      mares were inseminated with 800*10(6) sperm. The total number of sperm recovered
      was 7.8+/-4.7*10(9) for EJ-0h sperm, 12.9+/-9.2*10(9) for EP-0h sperm and 12.0+/
      8.0*10(9) for EP-24h sperm. The sperm motility, evaluated by total motility,
      progressive motility and the percentage of rapid cells, was similar among the
      samples before and after freezing (P>0.05). However, the plasma membrane
      integrity was different between EJ-0h and EP-0h pre-freezing and between EJ-0h
      and EP-24h post-thawing (P<0.05). The conception rates were similar between
      groups inseminated with sperm recovered from the epididymal cauda immediately
      after orchiectomy (EP-0h), after 24h of storage at 5 degrees C of the epididymal
      cauda (EP-24h) and with ejaculated sperm (EJ-0h) (P>0.05). In conclusion, the
      viability and fertility of cauda epididymal sperm are similar to those of
      ejaculated sperm.

PMID- 21890291
TI  - Parthenogenic blastocysts cultured under in vivo conditions exhibit proliferation
      and differentiation expression genes similar to those of normal embryos.
AB  - Parthenote embryos offer multiple possibilities in biotechnological
      investigation, such as stem cell research. However, there is still a dearth of
      knowledge of this kind of embryo. In this study, development and ploidy were
      analysed in parthenotes under in vitro and in vivo culture conditions.
      Subsequently, using real-time PCR, the expressions of factor OCT-4, Vascular
      Endothelial Growth Factor, Epidermal Growth Factor Receptor 3 and Transforming
      Growth Factor beta2 genes were analysed to compare the embryo types at the
      blastocyst stage. Development and implantation of parthenote embryos were
      described after transfer at day 10 of pregnancy. Parthenotes showed similar
      blastocyst development for both culture conditions and most of the parthenotes
      produced were diploid. However, parthenotes developed under in vivo conditions
      showed similar mRNA expression of OCT-4, VEGF and TGF-beta2 to 5 and 6 day old
      blastocysts. In contrast, parthenotes developed under in vitro conditions had
      altered the expression pattern of these genes, except for erbB3 mRNA. Finally,
      transferred parthenotes had the ability to implant but showed severe growth
      retardation and lesser size. This is the first demonstration of the influence of
      culture conditions on parthenote mRNA expression. Our study highlights the
      importance of culture conditions in subsequent uses of parthenotes, such as the
      production of stem cell lines.

PMID- 21890292
TI  - Management of type 2 diabetes mellitus in the elderly.
AB  - AIM: To provide evidence based recommendations for optimal care diabetes care in
      the elderly. BACKGROUND: Diabetes affects approximately 25% of the population
      >=65 years, and that percentage is increasing rapidly, particularly in minorities
      who represent an important fraction of the uninsured/underinsured. Diabetes is an
      important cause of hospital admissions and a co-morbidity in as high as 50% of
      hospital inpatients. It impacts mortality and quality of life. While tools have
      become available to improve glycemic control, enthusiasm for their application
      must be tempered with the sober realization of the risks involved in
      intensification of glycemic control, chiefly hypoglycemia. METHODS: Weighted
      review from PubMed and other literature search tools in descending order of
      randomized control trials, observational studies, pilot studies, published
      guidelines, the authors' clinical experience, and expert opinion.
      RESULTS/CONCLUSIONS: * HbA1c targets should be stratified according to the
      frailty of the elderly diabetic patient: <7.0% in the generally well elderly and
      < 8.0% in the frail elderly. * Therapies are available that achieve glycemic
      goals, while minimizing the risk of hypoglycemia, taking into consideration such
      factors as cognitive function, renal and hepatic function, bone density, fall
      risk, and hypoglycemia unawareness. * When insulin is used determir or glargine
      are safer choices than NPH. * Ultra-short acting prandial insulins are safer than
      regular insulin. * Pen devices for insulin delivery significantly reduce dosing
      errors and the risk of hypoglycemia. * Sudden managed care formulary changes that
      disrupt patients' diabetes treatment should be prevented through national policy
      initiatives. * Up to date home medication lists help prevent dangerous medication
      errors. * Widespread adoption of telehealth approaches can significantly improve
      glycemic control and render it safer.

PMID- 21890293
TI  - Forged seal detection based on the seal overlay metric.
AB  - This paper describes a method for verifying the authenticity of a seal impression
      imprinted on a document based on the seal overlay metric, which refers to the
      ratio of an effective seal impression pattern and the noise in the neighborhood
      of the reference impression region. A reference seal pattern is obtained by
      taking the average of a number of high-quality impressions of a genuine seal. A
      target seal impression to be examined, often on paper with some background texts
      and lines, is segmented out from the background by an adaptive threshold applied
      to the histogram of color components. The segmented target seal impression is
      then spatially aligned with the reference by maximizing the count of matching
      pixels. Then the seal overlay metric is computed for the reference and the
      target. If the overlay metric of a target seal is below a predetermined limit for
      the similarity to the genuine, then the target is classified as a forged seal. To
      further reduce the misclassification rate, the seal overlay metric is adjusted by
      the filling rate, which reflects the quality of inked pattern of the target seal.
      Experiment results demonstrate that the proposed method can detect elaborate seal
      impressions created by advanced forgery techniques such as lithography and
      computer-aided manufacturing.

PMID- 21890294
TI  - Blow flies (Diptera: Calliphoridae) survive burial: Evidence of ascending
      vertical dispersal.
AB  - This study was undertaken to determine if immature blow flies could complete
      development following burial and emerge from the soil as adults. Two species of
      blow flies, Cochliomyia macellaria and Protophormia terraenovae, were placed at
      three depths and at three different life stages, in a simulated burial to
      evaluate the impact of soil on ascending vertical dispersal and fly survival. In
      soil columns, immature stages of each species were covered with 5, 25 and 50cm of
      soil. Emerging adult flies of both species reached the surface from all depths at
      all three immature stages (2nd instar, 3rd instar and pupae). At the 50-cm depth,
      flies were least successful in reaching the surface when buried as pupae and most
      successful as late 3rd instar larvae (prepupae). Collectively, more adult flies
      emerged from the soil if buried as 3rd instars (79.6%) than either 2nd instars or
      pupae (59.6% and 59.3%, respectively (F(2,159)=14.76, P<0.0001)). Similarly, at
      shallow burial depths of 5 and 25cm, 75.6% and 70.4% of the adults successfully
      reached the surface, compared with 52.6% at the 50-cm depth (F(2,159)=15.95,
      P<0.0001). Second instars demonstrated ascending vertical dispersal behaviours in
      the soil column by pupating closer to the surface. Nearly half (46.6%) of the C.
      macellaria 2nd instars buried in 25cm of soil pupated nearer to the surface.
      Similarly, 45.4% of the P. terraenovae 2nd instars pupated nearer to the surface.
      When buried at 50cm, approximately 25% of 2nd instars of both species pupated
      nearer to the surface. When 3rd instars of C. macellaria and P. terraenovae were
      buried at 120cm, 40% and 4.3% of the adults, respectively, successfully reached
      the soil surface.

PMID- 21890295
TI  - Cerebral neoplastic enhancing lesions: multicenter, randomized, crossover
      intraindividual comparison between gadobutrol (1.0M) and gadoterate meglumine
      (0.5M) at 0.1 mmol Gd/kg body weight in a clinical setting.
AB  - OBJECTIVE: Two macrocyclic extracellular contrast agents, one-molar neutral
      gadobutrol and ionic gadoterate meglumine, were compared to determine the overall
      preference for one or the other in a clinical setting. MATERIALS AND METHODS:
      Multicenter, randomized, single-blind, intra-individually controlled, comparison
      study with a corresponding blinded read. Efficacy analysis was based on 136
      patients who underwent identical MRI examinations: group A first received 1.0M
      gadobutrol followed by 0.5M gadoterate meglumine 48 h to 7 days later; group B
      had a reversed administration order. Three independent blinded readers assessed
      off-site their overall diagnostic preference (primary efficacy parameter) based
      on a matched pairs approach. RESULTS: Superiority of gadobutrol over gadoterate
      meglumine was demonstrated for the qualitative assessment of overall preference
      across all readers by a statistically significant difference between both
      contrast agents for this primary endpoint. Preferences in lesion enhancement
      (secondary endpoint) were also found significantly in favor of gadobutrol. For
      preference in lesion delineation from surrounding tissue/edema and for internal
      structure only a trend towards a higher proportion for gadobutrol was found
      (except for internal structure reported by one reader, which showed a result of
      statistical significance). Lesion contrast and relative lesion enhancement
      (quantitative parameters) were statistically significantly higher for gadobutrol
      compared to gadoterate meglumine. CONCLUSION: Contrast-enhanced MRI of neoplastic
      brain lesions at a dose of 0.1 mmol Gd/kg body weight, assessed in a standardized
      off-site blinded reading, results in a significantly higher qualitative and
      quantitative preference for gadobutrol compared to gadoterate meglumine.

PMID- 21890296
TI  - Development and validation of a dried blood spot LC-MS/MS assay to quantify
      ranitidine in paediatric samples.
AB  - A novel approach has been developed to determine ranitidine in paediatric samples
      using dried blood spots (DBS) on Guthrie cards (Whatman 903). A selective and
      sensitive HPLC-MS/MS assay has been developed and validated using small volumes
      of blood (30 MUl). A 6 mm disc was punched from each DBS and extracted with
      methanolic solution of the internal standard (IS) nizatidine. This was further
      subjected to solid phase extraction (SPE), followed by reversed phase HPLC
      separation, using a XBridgeTM C18 column and mobile phase 10 mM ammonium
      acetate/methanol (98:2 v/v) with a flow rate of 0.3 mL/min. This was combined
      with multiple reaction monitoring (MRM) mass detection using electrospray
      ionisation (ESI). The calibration curve for ranitidine was found linear over the
      range 10-500 ng/mL (r=0.996). The limit of quantification (LOQ) of the method was
      validated at 10 ng/mL. Accuracy and precision values for within and between days
      were <20% at the LOQ and <15% at all other concentrations. The validated DBS
      method was successfully applied to a clinical study employing 81 samples from 36
      paediatric patients.

PMID- 21890297
TI  - Determination of berberine, palmatine and jatrorrhizine in rabbit plasma by
      liquid chromatography-electrospray ionization-mass spectrometry.
AB  - Incurred rabbit plasmas samples were utilized for method quality assessment in
      this study, where an optimized protein precipitation method for the preparation
      of rabbit plasma samples and a rapid and sensitive liquid chromatography
      electrospray ionization-mass spectrometry for the simultaneous determination of
      berberine, palmatine and jatrorrhizine was described. Plasma samples (100 MUl)
      were pretreated by protein precipitation with the mixture of 3% formic acid and
      50 ng/ml clozapine (internal standard) in acetonitrile followed by LC analysis
      using a C(18) column and a mobile phase composed of 0.4% formic acid solution and
      0.2% formic acid solution of methanol (60:40, v/v) operated at a flow rate of 0.4
      ml/min. The analysis was performed in the multiple reaction monitoring mode via
      electrospray ionization source operating in the positive ionization mode. The
      method was linear over the concentration range of 0.1-400 ng/ml for all target
      components. The lower limits of quantification were 0.1 ng/ml for all analytes,
      all intra- and inter-day precision values were less than 7.10%, and accuracy
      (bias, %) was within +/-7.11%. The mean absolute recovery was more than 72% for
      all analytes. The validated method has been successfully applied to the
      pharmacokinetic study of berberine, palmatine and jatrorrhizine in rabbit plasma
      after oral administration of San-Huang decoction to rabbits.

PMID- 21890298
TI  - Determination and characterization of degradation products of anastrozole by LC
      MS/MS and NMR spectroscopy.
AB  - Two new degradation products for Anastrozole active pharmaceutical ingredient
      (ANZ) have been identified and reported in this paper. The ANZ was subjected to
      thermal, photolytic, oxidative and base stress conditions prescribed by ICH
      guidelines. Separation of ANZ from its existing impurities and the two new
      impurities was achieved by using on Oyster ODS-3 (100 mm*4.6 mm*3.0 MUm) column
      with an isocratic mixture of 10 mM ammonium formate and acetonitrile in the ratio
      60:40 (v/v). The flow rate was 0.5 ml min(-1). The elution was monitored at 215
      nm. An isocratic stability indicating reverse phase liquid chromatographic (RP
      LC) and LC-MS/MS method was developed for the determination of purity and assay
      of ANZ through forced degradation studies. The two new impurities detected were
      further subjected to spectroscopic studies. Based on the results obtained from
      the different spectroscopic studies, these impurities have been characterized as
      2,2'-(5-((1H-1,2,4-triazol-1-yl)methyl)-1,3-phenylene)bis(2-methylpropanoicacid)
      (Diacid) and 2-(3-((1H-1,2,4-triazol-1-yl)methyl)-5-(2-cyanopropan-2-yl)phenyl)-2
      methylpropanoicacid (Monoacid). ANZ was found to degrade in base, slightly in
      oxidative degradation conditions. The degradation products were well resolved
      from main peak and its impurities thus proved the stability, indicating power of
      the method. The developed method was validated as per International Conference on
      Harmonization (ICH) guidelines with respect to specificity, limit of detection,
      limit of quantitation, precision, linearity, accuracy, robustness and system
      suitability.

PMID- 21890299
TI  - Disparities in patient reports of communications to inform decision making in the
      DECISIONS survey.
AB  - OBJECTIVE: To identify patient- and decision-type predictors of two key aspects
      of informed decision making: discussing the cons (not just the pros) of medical
      interventions and asking patients what they want to do. METHODS: Using data from
      2473 members of the DECISIONS survey, a nationally representative sample of U.S.
      adults age 40+, we used logistic regression analysis to identify which patient
      characteristics predicted patient reports of healthcare providers discussing cons
      or eliciting preferences about one of 9 common medical decisions. RESULTS:
      Multiple demographic characteristics predicted both discussions of cons and
      elicitations of preferences, although the specific characteristics varied between
      decision contexts. In particular, African-American respondents reported being
      more likely to receive a discussion of the cons of cancer screening (OR=1.69,
      p<0.05) yet less likely to have been asked their opinion about either getting a
      cancer screening test (OR=0.56, p<0.05) or initiating medications (OR=0.53,
      p<0.05). Significant cross-decision variations remained even after controlling
      for patient characteristics. CONCLUSIONS: Important disparities in patient
      communication and involvement appear to exist both between different types of
      medical decisions and between different types of patients. PRACTICE IMPLICATIONS:
      Providers must make sure to consistently discuss the cons of treatment and to
      solicit input from all patients, especially African-Americans.

PMID- 21890300
TI  - Does motivational interviewing counseling time influence HIV-positive persons'
      self-efficacy to practice safer sex?
AB  - OBJECTIVE: This study examined the impact of motivational interviewing (MI)
      counseling time on self-efficacy to practice safer sex for people living with
      HIV/AIDS (PLWHA). METHODS: In 4 month intervals we followed a cohort of 490 PLWHA
      for 12 months. We conducted hierarchical linear regression models to examine
      changes in safer sex self-efficacy when participants received zero, low to
      moderate (5-131 min) and high (132-320 min) doses of MI time. We conducted a
      similar analysis using number of counseling sessions as the predictor variable.
      RESULTS: Participants with low to moderate doses of MI counseling had 0.26 higher
      self-efficacy scores than participants with zero MI time (p=0.01). Also, they had
      0.26 lower self-efficacy scores than participants with high amounts of MI time
      (p=0.04). Participants with high doses of MI had a 0.5 higher self-efficacy score
      than participants with zero amount of MI time (p<0.0001). Participants who
      received 3-4 counseling sessions had 0.41 greater self-efficacy scores than
      participants who did not receive any sessions (p<0.0001) but did not differ from
      participants receiving 1-2 sessions. CONCLUSION: MI time is a key to enhancing
      safer sex self-efficacy among PLWHA. PRACTICE IMPLICATIONS: Safer sex self
      efficacy improves the more MI counseling time and sessions PLWHA receive.

PMID- 21890301
TI  - The doctor and the patient--how is a clinical encounter perceived?
AB  - OBJECTIVE: To examine the population distribution of different types of
      relationships between people with chronic conditions and their doctors that
      influence decisions being made from a shared-decision making perspective.
      METHODS: A survey questionnaire based on recurring themes about the
      doctor/patient relationship identified from qualitative in-depth interviews with
      people with chronic conditions and doctors was administered to a national
      population sample (n=999) of people with chronic conditions. RESULTS: Three
      factors explained the doctor/patient relationship. Factor 1 identified a positive
      partnership characteristic of involvement and shared decision-making; Factor 2
      doctor-controlled relationship; Factor 3 relationship with negative dimensions.
      Cluster analysis identified four population groups. Cluster 1 doctor is in
      control (9.7% of the population); Cluster 2 ambivalent (27.6%); Cluster 3
      positive long-term relationship (58.6%); Cluster 4 unhappy relationship (4.4%).
      The proportion of 18-34 year olds is significantly higher than expected in
      Cluster 4. The proportion of 65+ year olds is significantly higher than expected
      in Cluster 1, and significantly lower than expected in Cluster 4. CONCLUSION:
      This study adds to shared decision-making literature in that it shows in a
      representative sample of people with chronic illnesses how their perceptions of
      their experiences of the doctor-patient relationship are distributed across the
      population. PRACTICE IMPLICATIONS: Consideration needs to be given as to whether
      it is better to help doctors to alter their styles of interactions to suit the
      preferences of different patients or if it is feasible to match patients with
      doctors by style of decision-making and patient preference.

PMID- 21890302
TI  - Soluble p-selectin, D-dimer, and high-sensitivity C-reactive protein after acute
      deep vein thrombosis of the lower limb.
AB  - BACKGROUND: Soluble p-selectin (sP-selectin), D-dimer, and C-reactive protein
      (CRP) are elevated in deep vein thrombosis (DVT), and may play a role as risk
      predictors of recurrent venous thromboembolism. However, these parameters have
      only been assessed at manifestation or at single time points after DVT so far. We
      therefore investigated the course of sP-selectin, D-dimer, and high-sensitivity
      (hs)-CRP after acute unprovoked DVT of the lower limb. METHODS: In this
      prospective, longitudinal study, sP-selectin, D-dimer, and hs-CRP were determined
      by enzyme-linked immunosorbent assay, quantitative latex assay, and particle
      enhanced immunonephelometry, respectively, in 44 patients with sonographically
      confirmed acute DVT at the time of diagnosis, and 1, 3, 6, and 12 months later.
      sP-selectin and hs-CRP were also measured in 88 age- and gender-matched healthy
      controls. Further, color duplex sonography was performed in all patients at each
      time point. RESULTS: At DVT diagnosis, sP-selectin and hs-CRP were significantly
      higher in patients compared with healthy controls. From baseline to 1 month, both
      parameters decreased significantly. In patients with oral anticoagulation (OAC)
      for 6 months (n = 35), levels of sP-selectin increased significantly after
      cessation of anticoagulant therapy (P = .002), while sP-selectin was similar to
      healthy controls in patients with ongoing OAC (n = 9) at 12 months (P = .49). In
      contrast, hs-CRP in both subgroups remained constantly low at levels seen in
      healthy controls. The course of D-dimer was similar to sP-selectin. Color duplex
      sonography showed no ongoing thrombus formation in any patient. Thirty-four
      (77.3%), 29 (65.9%), 26 (59.1%), and 25 (56.8%) patients had residual thrombosis
      1, 3, 6, and 12 months after the acute event, respectively. D-dimer was
      significantly higher in patients with residual thrombosis compared with patients
      without residual thrombosis 1 month after DVT (0.58 MUg/mL [range, 0.2-9.67
      MUg/mL] vs 0.25 MUg/mL [range, 0.2-0.62 MUg/mL]; P = .02). At all other time
      points, the levels of D-dimer and sP-selectin did not differ significantly
      between patients without and with residual thrombosis (all P > .05). CONCLUSIONS:
      Concentrations of sP-selectin and D-dimer after acute DVT seem to be strongly
      influenced by treatment with vitamin K antagonists. After withdrawal of oral
      anticoagulation, they rise again and could therefore reflect a prothrombotic
      state, which is susceptible to pharmacologic therapy.

PMID- 21890303
TI  - New method for absolute spinal cord ischemia protection in rabbits.
AB  - OBJECTIVE: This study aims to establish a superior procedure to prevent spinal
      cord damage after severe spinal cord ischemia during aortic surgery. We examined
      the synergistic effect of topical hypothermia of the spinal cord combined with
      radical scavenger infusion into the clamped segment of the aorta to prevent
      spinal cord damage in an animal model. METHODS: Spinal cord ischemia was induced
      in rabbits by clamping the aorta between the renal artery and aortic bifurcation
      for 30 minutes. Rabbits were divided into four groups of 16 each: group I, sham
      operated; group II, edaravone (6 mL, 4 degrees C, 1 mg/kg); group III, saline (6
      mL, 4 degrees C) with transvertebral cooling pads; group IV, edaravone (6 mL, 4
      degrees C, 1 mg/kg) and transvertebral cooling pads. Solutions were injected into
      the clamped segment of the aorta. Postoperative assessments included the Tarlov
      score, spinal cord histopathology, and measurement of malondialdehyde levels in
      the spinal cord tissue. RESULTS: At 48 hours after reperfusion, the mean Tarlov
      scores in groups I, II, III, and IV were 4.0, 1.5, 1.9, and 4.0, respectively.
      The mean number of normal motor neurons was significantly higher in groups I
      (54.1) and IV (53.7) than in groups II (32.8) and III (36.3; P < .001). The mean
      malondialdehyde level in groups I (19.8 nmol/mL) and IV (22.6 nmol/mL) was
      significantly lower than in groups II (64.8 nmol/mL) and III (60.9 nmol/mL; P <
      .001). At 168 hours after reperfusion, the mean Tarlov scores in groups I, II,
      III, and IV were 4.0, 1.1, 1.3, and 4.0, respectively. The mean number of normal
      motor neurons was significantly higher in groups I (52.9) and IV (50.8) than in
      groups II (22.4) and III (25.9; P < .001). The mean malondialdehyde level in
      groups I (20.7 nmol/mL) and IV (23.4 nmol/mL) was significantly lower than in
      groups II (68.9 nmol/mL) and III (61.6 nmol/mL; P < .001). CONCLUSION: In a
      rabbit model with aortic clamping up to 30 minutes, which consistently produces
      complete paraplegia in rabbits, spinal cord damage was partially reduced by
      topical cooling with transvertebral cooling pads or the injection of edaravone
      into the clamped segment of aorta, but was more effectively protected by a
      combined use of these two strategies.

PMID- 21890304
TI  - Pioglitazone prevents intimal hyperplasia in experimental rabbit vein grafts.
AB  - BACKGROUND: Intimal hyperplasia is a major obstacle to patency after vein
      grafting. Several clinical trials revealed that pioglitazone, a peroxisome
      proliferator-activated receptor-gamma ligand, exerts beneficial actions on
      cardiovascular complications. We investigated whether pioglitazone modulates
      intimal hyperplasia in experimental rabbit autologous vein grafts. METHODS: Male
      Japanese White rabbits were randomly divided into two groups: one group received
      pioglitazone as food admixture at a concentration of 0.01%, and the other did not
      (control). One week later, each group underwent reversed autologous vein bypass
      grafting of the right common carotid artery using ipsilateral external jugular
      vein. Pioglitazone therapy was continued after surgery and until harvest. Intimal
      hyperplasia of the grafted vein was assessed at 28 days. Two weeks after
      implantation, proliferative cells in the neointima were identified by
      immunohistochemical staining with Ki-67 monoclonal antibody. To determine
      apoptotic cells, we performed terminal deoxynucleotidyl transferase-mediated
      deoxyuride-5'-triphosphate nick-end labeling (TUNEL) staining. Blood samples were
      collected at 28 days after implantation for measuring metabolic parameters such
      as plasma glucose and total cholesterol. Adiponectin levels were determined by
      Western blot analysis. Finally, we assessed adiponectin-related signaling
      pathway, 5' adenosine monophosphate-activated protein kinase (AMPK), and
      extracellular signal-regulated kinase (ERK) in the grafted vein by Western blot
      analysis. RESULTS: Treatment with pioglitazone markedly inhibited intimal
      hyperplasia of carotid interposition-reversed jugular vein grafts in the
      pioglitazone group (0.54 +/- 0.04 mm(2)) vs control (0.93 +/- 0.04 mm(2); n = 7;
      P < .01). Pioglitazone treatment reduced the number of Ki-67-positive
      proliferating cells in the neointima of the vein grafts at 14 days after
      implantation in the pioglitazone group (4.1% +/- 1.1%) vs the controls (16.8% +/-
      1.7%; P < .05). The frequency of TUNEL-positive apoptotic cells was enhanced by
      pioglitazone (3.5% +/- 0.5%) vs the controls (1.2% +/- 0.1%; P < .05).
      Pioglitazone treatment also increased plasma levels of adiponectin, a vascular
      protective hormone, and led to an increase in phosphorylation of AMPK and a
      decrease in phosphorylation of ERK in the grafted vein. CONCLUSIONS: Pioglitazone
      attenuates intimal hyperplasia of the vein graft after autologous bypass grafting
      by its ability to suppress cell proliferation and enhance apoptosis. Pioglitazone
      could represent a therapeutic target for the prevention of graft failure after
      bypass grafting.

PMID- 21890305
TI  - Novel use of endoluminal repair as prophylaxis of aortic rupture secondary to
      radiotherapy for lung cancer.
AB  - Non-small-cell lung cancer (NSCLC) invading the aorta is staged as T(4). Only 9%
      of T(4) tumors are resected; the alternative is chemoradiotherapy, but for peri
      aortic NSCLC, radiation damage to the aortic wall can induce fatal rupture. We
      report the case of a 76 year-old man with a 3-cm left lower lobe NSCLC clearly
      invading the aortic wall. A thoracic stent graft was inserted prophylactically to
      prevent aortic rupture. He then received 64 Gy radiotherapy in 32 fractions,
      resulting in tumor shrinkage. Prophylactic aortic endografting, a less invasive
      treatment than open surgery, may enable high dose irradiation of the aortic wall.

PMID- 21890306
TI  - Sugarcane biopolymer patch in femoral vein angioplasty on dogs.
AB  - PURPOSE: To evaluate the use of the sugarcane biopolymer membrane in femoral vein
      patch angioplasty on dogs. METHODS: Eight dogs were submitted to bilateral
      femoral vein patch angioplasty with a sugarcane biopolymer membrane patch on one
      side and an expanded polytetrafluoroethylene (e-PTFE) patch on the contralateral
      side. This research was performed at Experimental Surgical Research Laboratory of
      the Centro de Ciencias da Saude at Universidade Federal de Pernambuco. The dogs
      underwent new surgery at 180 days after the patch angioplasty in order to harvest
      the femoral vein. All the animals were evaluated by clinical examination, measure
      of femoral vein diameter, venogram, and Doppler fluxometry. The material
      harvested was sent for histologic study. Each animal served as its own control.
      RESULTS: In all veins of both groups, there were no cases of infection, rupture,
      or pseudoaneurysm formation and thrombosis. In both groups, a chronic
      inflammatory reaction was observed, with lymphocytes, neutrophils, and fibrosis
      in the outer surface of the patches. Fibrosis was seen in the inner surfaces of
      all the patches. In e-PTFE patches, invasion by fibroblasts occurred.
      CONCLUSIONS: The sugarcane biopolymer membrane can be used as a patch in femoral
      vein angioplasty on dogs. CLINICAL RELEVANCE: The sugarcane biopolymer membrane
      is easily synthesized with a low cost of production. This membrane has been used
      in many areas of experimental surgery as in the healing of skin wounds, in
      urinary reconstruction, in reconstruction of tympanic membrane, and as an
      arterial substitute, but there is no report of its use as a vein substitute. In
      order to evaluate the possibility of using the sugarcane biopolymer membrane in
      venous reconstructive surgery, this study analyzed its utilization in femoral
      vein patch angioplasty.

PMID- 21890307
TI  - The results of a simplified technique for safe carotid stenting in the elderly.
AB  - PURPOSE: The purpose of this study was to report the preliminary experience of a
      modified transcervical carotid angioplasty and stenting (CAS) technique with
      filter protection and flow reversal only during filter placement in patients
      unsuitable for transfemoral CAS and at high risk for carotid endarterectomy
      (CEA). PATIENTS AND METHODS: Twenty-five of 132 patients, aged 75 to 86 years
      old, with severe carotid stenosis had been selected. Eighteen patients had
      transient ischemic attacks (TIAs) in the last month and seven patients were
      asymptomatic. Patients with limited life expectancy were not included. The common
      carotid artery (CCA) was mobilized and cannulated. The flow in the internal
      carotid artery (ICA) was reversed by occluding the proximal CCA and connecting
      the introducing sheath to a blood transfusion bag positioned close to the floor,
      instead of returning it directly to the venous system. This produced retrograde
      flow in the ICA in all patients as a result of greater pressure gradient. The
      carotid filter was inserted to the distal ICA under retrograde flow and then
      antegrade flow was resumed and CAS was performed. All patients were
      autotransfused except for four patients who had severe renal insufficiency to
      avoid readministration of contrast media. RESULTS: All procedures were successful
      except in one patient converted to open endarterectomy because of CCA dissection
      (technical success rate 97.5%) and one patient who had a TIA involving the right
      hand 10 hours after CAS and recovered completely after 3 hours (event rate 2.5%).
      Reversed flow was visualized with intraoperative angiography in the ICA in all
      patients. Twenty-two patients were discharged the next morning and three (12%) on
      the following day because of hypotension. The duration of reversed flow was 1 to
      4 minutes (mean, 1.5 minutes), the amount of blood collected was 100 to 400 mL
      (mean, 250 mL), and none of these patients had any hemodynamic disturbance during
      the procedure. Creatinine levels showed no increase postoperatively in either
      patient. The patients were followed-up clinically and with color Duplex scan for
      3 to 24 months, so far, and they are free of symptoms or significant restenosis.
      CONCLUSION: The results of this preliminary study indicate that the transcervical
      approach with flow reversal during the insertion of the protecting filter allows
      CAS with minimal interruption of cerebral circulation and is simple and safe in
      patients unsuitable for CEA and transfemoral CAS for anatomic reasons. Further
      research with randomization and with pre-procedure and post-procedure diffusion
      weighted magnetic resonance imaging (DW-MRI) is required in order to expand the
      indications of this method.

PMID- 21890308
TI  - Oxygen uptake before and after the onset of claudication during a 6-minute walk
      test.
AB  - OBJECTIVE: This study compared oxygen uptake before and after the onset of
      claudication in individuals with peripheral artery disease (PAD) during a 6
      minute walk test, and identified predictors of the change in oxygen uptake after
      the onset of claudication pain. METHODS: The study included 50 individuals with
      PAD. During a 6-minute walk test, 33 experienced claudication (pain group), and
      17 were pain-free (pain-free group). Oxygen uptake and ambulatory cadence were
      the primary outcomes evaluated during the 6-minute walk test. RESULTS: The pain
      group experienced onset of claudication pain at a mean (standard deviation) of
      179 (45) meters and continued to walk to achieve a 6-minute walk distance of 393
      (74) meters, which was similar to the 401 (76) meters walked in the pain-free
      group (P = .74). Oxygen uptake increased (P < .0001) after the onset of pain in
      the pain group, and this change was greater (P = .025) than the increase in
      oxygen uptake from the second to fifth minutes of walking in the pain-free group.
      Ambulatory cadence decreased after the onset of pain in the pain group (P =
      .0003). The change in oxygen uptake was associated with metabolic syndrome (P =
      .0023), 6-minute walk distance (P = .0037), age (P = .0041), and oxygen uptake
      during the second minute of the test (P = .012). CONCLUSION: Claudication
      increases oxygen uptake of self-paced, over-the-ground ambulation, despite a
      decrease in cadence. The pain-mediated increase in oxygen uptake was blunted in
      individuals with metabolic syndrome, suggesting that the ability to increase
      oxygen uptake during ambulation is impaired. The clinical significance is that
      claudication increases the metabolic cost of ambulation, thereby increasing the
      relative intensity of exercise and reducing the tolerance to sustain ambulation.

PMID- 21890309
TI  - Surveillance of a coiled renal artery aneurysm by contrast-enhanced ultrasound
      with Definity.
AB  - Imaging surveillance is necessary to assess for long-term procedural outcomes
      after endovascular treatment. This is generally performed by computed tomography
      (CT) or magnetic resonance imaging (MRI). Contrast-enhanced ultrasound (CEUS) has
      recognized utility for cardiovascular and abdominal applications and is an
      alternative option in patients with renal impairment or CT/MR contrast-related
      reactions. We believe that we present the first reported case of CEUS in the
      surveillance of a treated renal artery aneurysm. The 57-year-old patient had a
      severe CT contrast allergy. CEUS performed with Definity microbubble ultrasound
      contrast (Lantheus Medical Imaging, Billerica, Mass) was well tolerated and
      showed no residual filling of the aneurysm.

PMID- 21890310
TI  - Common femoral endovenectomy with iliocaval endoluminal recanalization improves
      symptoms and quality of life in patients with postthrombotic iliofemoral
      obstruction.
AB  - BACKGROUND: The postthrombotic syndrome is a debilitating condition occurring in
      30% to 50% of patients with lower extremity deep vein thrombosis (DVT). Following
      iliofemoral DVT, however, postthrombotic morbidity is especially severe, due to
      occlusion of the common femoral vein (CFV) and iliac veins. While endoluminal
      recanalization appears effective in restoring patency to the iliac venous system,
      infrainguinal obstruction of the CFV remains a problem. The purpose of this study
      is to report preliminary observations of common femoral endovenectomy and
      intraoperative endoluminal recanalization of the iliac veins in patients with
      incapacitating postthrombotic iliofemoral obstruction. METHODS: Ten patients
      underwent common femoral endovenectomy with endoluminal iliocaval recanalization.
      The Venous Clinical Severity Score (VCSS), a validated tool to assess chronic
      venous disease, the Villalta scale, a validated tool to quantify postthrombotic
      syndrome, the clinical classification of CEAP, and the Venous Insufficiency
      Epidemiological and Economic Study-Quality of Life (VEINES-QOL)/Sym
      questionnaires were completed preoperatively and readministered postoperatively
      at 8.8 months (mean). RESULTS: Five patients were followed for more than 6 months
      and form the basis of the long-term analysis. All demonstrated significant
      improvement in their venous scores postoperatively. The VCSS preoperatively was
      17 and fell to 9.8 postoperatively (P = .02). The Villalta scale dropped from
      13.6 preoperatively to 6.0 postoperatively (P = .002). The VEINES-QOL/Sym
      questionnaire, a sensitive marker of patient quality of life and symptom status,
      was improved (P = .01 and .02, respectively). CONCLUSION: Chronic postthrombotic
      iliofemoral venous obstruction treated with common femoral endovenectomy and
      endoluminal recanalization improves objective outcome measures of patients with
      chronic postthrombotic obstruction. By restoring unobstructed venous drainage
      through the CFV to the vena cava, patients' postthrombotic morbidity is reduced
      and quality of life is improved.

PMID- 21890311
TI  - Poly-L/D-lactic acid anchors are associated with reoperation and failure of SLAP
      repairs.
AB  - PURPOSE: This study investigates factors associated with failure and reoperation
      after glenoid labrum repair. METHODS: We studied a nonconcurrent cohort of
      consecutive patients undergoing arthroscopic superior labrum repair at a single
      institution by 2 fellowship-trained surgeons over a 10-year period. RESULTS:
      There were 348 patients included in this study with a mean age of 33.4 years (95%
      confidence interval [CI], 32.1 to 35.9) and a mean clinical follow-up of 12.3
      months (95% CI, 10.9 to 13.8). The overall reoperation rate was 6.3%, with a
      revision labrum repair rate of 4.3%. Subsequent surgery and failure after
      arthroscopic labrum repair were significantly correlated with Workers'
      Compensation claims (odds ratio [OR], 4.6; P < .001; 95% CI, 1.8 to 11.7), the
      use of tobacco (OR, 12.0; P = .03; 95% CI, 1.2 to 114.9), and the use of
      absorbable poly-L/D-lactic acid (PLDLA) anchors (100% correlation, P < .001). The
      OR for having repeat surgery was 12.7 (95% CI, 4.9 to 32.9; P < .001) with poly
      96L/4D-lactic acid (Mini-Revo; Linvatec, Largo, FL) and also increased with the
      use of poly-70L/30D-lactic acid (Bio-Fastak and Bio-Suturetak; Arthrex, Naples,
      FL) anchor material (P = .04) after removal of the patients exposed to poly
      96L/4D-lactic acid anchors. The rates of repeat surgery with PLDLA anchors from
      Linvatec and PLDLA anchors from Arthrex were 24% and 4%, respectively. None of
      the patients treated with nonabsorbable suture anchors (polyether ether ketone or
      metallic) returned to the operating room (P < .001). After we controlled for
      associated factors in a multivariate analysis, the use of absorbable anchors, in
      particular poly-96L/4D-lactic acid anchors (OR, 14.7; P < .001), and having a
      work-related injury (OR, 8.1; P < .001) remained independent factors associated
      with both repeat surgery and revision superior labrum repair. CONCLUSIONS:
      Bioabsorbable PLDLA anchor material led to significantly more SLAP repair
      failures and reoperations compared with nonabsorbable suture anchors. Our
      recommendation is that glenoid labrum repairs be performed with nondegradable
      material and, specifically, that the use of anchors composed of PLDLA material
      should be avoided.

PMID- 21890312
TI  - [Innovative therapeutics for idiopathic pulmonary fibrosis].
AB  - Idiopathic pulmonary fibrosis (IPF), the most common and severe interstitial lung
      disease, remains a great challenge for clinicians. The natural history of the
      disease is incompletely understood and its prognosis is as devastating as that of
      many cancers. The most recent international consensus conference on IPF does not
      recommend any specific medical treatment and underlines the role of symptomatic
      care and management of co-morbidities, as well as lung transplantation, which
      should be openly discussed with the patient, if applicable, without delay. The
      lack of efficacy observed with steroids and immunosuppressive agents argues the
      current pathogenic hypothesis consistent with an abnormal alveolar epithelium
      wound healing after repeated injury. Thus, a need for anti-fibrosing and
      epithelial protective drugs emerged. Considerable progress has been made
      regarding the validation of relevant endpoints for clinical trials on IPF and
      pathogenesis, these two aspects of research being a framework for the exploration
      of new therapeutic approaches. Pirfenidone is the first drug that has been
      approved by health-care system for IPF treatment in Japan and in Europe. Many
      novel and promising drugs based on recent targets are under investigation.
      Combined therapies targeting different pathogenic pathways may represent the
      future for the treatment of IPF.

PMID- 21890313
TI  - [Thromboembolic events and air travel].
AB  - Relation between air travel and thromboembolic events is clearly demonstrated.
      The risk increases for travel of more than 5,000 km. Women are suspected to have
      an increased risk. However, the role of other potential thromboembolic risk
      factors remains unknown. The role of hypoxia and hypobaria, of the class traveled
      and of usual thromboembolic risk factors are unclear. Then, prophylactic strategy
      has to be decided regarding risk related to both travel and patient.
      Compartmental prophylactic therapy is largely indicated. Elastic stocking is
      widely recommended. Pharmacologic prophylactic therapy should be rarely indicated
      and discussed case by case.

PMID- 21890314
TI  - Quantifying cardiovascular risks in patients with metabolic syndrome undergoing
      total joint arthroplasty.
AB  - The coexistence of diabetes, hypertension, obesity, and dyslipidemia is defined
      as metabolic syndrome. Studies show substantial cardiovascular risks among these
      patients. The risk of patients with metabolic syndrome undergoing total joint
      arthroplasty (TJA) is unknown. Patients with and without metabolic syndrome
      undergoing TJA during a 3-year period were analyzed for postoperative
      complications. Metabolic syndrome was defined by having 3 of the following 4
      criteria: obesity (body mass index >=30 kg/m(2)), dyslipidemia, hypertension, and
      diabetes. Patients with metabolic syndrome had a significantly higher risk of
      cardiovascular complications compared with controls (P = .017). The risk of an
      adverse event increased by 29% and 32%, respectively, when there were 3 or 4
      syndrome components. Patients with metabolic syndrome undergoing TJA have
      increased risk for cardiovascular complications. Our results show that metabolic
      syndrome may have a clustering effect and pose increased risk when individual
      risks factors are combined.

PMID- 21890315
TI  - Clinical comparison of valgus and varus deformities in primary total knee
      arthroplasty following midvastus approach.
AB  - The purpose of this retrospective study was to compare clinical parameters in
      preoperative, perioperative, and postoperative categories between valgus and
      varus deformities in primary total knee arthroplasty (TKA) following midvastus
      approach. We compared 83 patients (83 TKAs in valgus) with 949 patients (1084
      TKAs in varus), with a mean follow-up of 72 months. In valgus deformity, mean age
      and body mass index at TKA were younger and smaller with more percentage of
      patellar subluxation. Cutting thickness from distal femur, tibial plateau, and
      lateral aspect of posterior femur were significantly different. The incidence of
      lateral release was 10.8% in valgus and 2.1% in varus. Although several
      significant differences were observed in preoperative and perioperative
      categories, the postoperative functional results were similarly evaluated by Knee
      Society knee and function scores.

PMID- 21890316
TI  - Health anxiety and attentional bias: the time course of vigilance and avoidance
      in light of pictorial illness information.
AB  - Cognitive-behavioral models of health anxiety stress the importance of selective
      attention not only towards internal but also towards external health threat
      related stimuli. Yet, little is known about the time course of this attentional
      bias. The current study investigates threat related attentional bias in
      participants with varying degrees of health anxiety. Attentional bias was
      assessed using a visual dot-probe task with health-threat and neutral pictures at
      two exposure durations, 175ms and 500ms. A baseline condition was added to the
      dot-probe task to dissociate indices of vigilance towards threat and difficulties
      to disengage from threat. Substantial positive correlations of health anxiety,
      anxiety sensitivity, and absorption with difficulties to disengage from threat
      were detected at 500ms exposure time. At an early stage (i.e., at 175ms exposure
      time), we found significant positive correlations of health anxiety and
      absorption with orientation towards threat. Results suggest a vigilance avoidance
      pattern of selective attention associated with pictorial illness related stimuli
      in health anxiety.

PMID- 21890317
TI  - Comorbidity of physical and motor problems in children with autism.
AB  - Autism and the related pervasive developmental disorders are a heavily researched
      group of neurodevelopmental conditions. In addition to core symptoms, there are a
      number of other physical and motor conditions that co-occur at high rates. This
      paper provides a review of factors and behaviors that correlate highly with
      disorders on the autism spectrum. Among these conditions are premature birth,
      birth defects, gross and fine motor skills, and obesity. Each of these topics is
      addressed, and what researchers have found are presented. These data have
      important implications for the types of collateral behaviors that should be
      assessed and treated, along with the core symptoms of autism.

PMID- 21890318
TI  - Reduction of restraint of people with intellectual disabilities: an
      organizational behavior management (OBM) approach.
AB  - We used an organizational behavior management (OBM) approach to increase behavior
      intervention plans and decrease the use of mechanical restraint. First,
      recipients were tracked as a member of the priority group if they engaged in
      frequent self-injurious behavior or physical aggression toward others and/or if
      they had been placed in mechanical restraint as a result of the problem
      behaviors. Second, a behavior data monitoring and feedback system was put in
      place. Third, organizational contingencies for the use of mechanical restraint or
      the occurrence of frequent self-injurious behavior or physical aggression toward
      others were initiated. Over the course of 17 months, behavior intervention plans
      were more than doubled to 124 and mechanical restraints decreased by almost 80%.
      This study represents the first to use an organizational behavior management
      (OBM) to reduce restraint with people who have intellectual disabilities.

PMID- 21890319
TI  - A coordinate descent margin based-twin support vector machine for classification.
AB  - Twin support vector machines (TWSVMs) obtain faster learning speed by solving a
      pair of smaller SVM-type problems. In order to increase its efficiency further,
      this paper presents a coordinate descent margin based twin vector machine
      (CDMTSVM) compared with the original TWSVM. The major advantages of CDMTSVM lie
      in two aspects: (1) The primal and dual problems are reformulated and improved by
      adding a regularization term in the primal problems which implies maximizing the
      "margin" between the proximal hyperplane and bounding hyperplane, yielding the
      dual problems to be stable positive definite quadratic programming problems. (2)
      A novel coordinate descent method is proposed for our dual problems which leads
      to very fast training. As our coordinate descent method handles one data point at
      a time, it can process very large datasets that need not reside in memory. Our
      experiments on publicly available datasets indicate that our CDMTSVM is not only
      fast, but also shows good generalization performance.

PMID- 21890320
TI  - Joining distributed pattern processing and homeostatic plasticity in recurrent on
      center off-surround shunting networks: noise, saturation, short-term memory,
      synaptic scaling, and BDNF.
AB  - The activities of neurons vary within small intervals that are bounded both above
      and below, yet the inputs to these neurons may vary many-fold. How do networks of
      neurons process distributed input patterns effectively under these conditions? If
      a large number of input sources intermittently converge on a cell through time,
      then a serious design problem arises: if cell activities are sensitive to large
      inputs, then why do not small inputs get lost in internal system noise? If cell
      activities are sensitive to small inputs, then why do they not all saturate at
      their maximum values in response to large inputs and thereby become incapable of
      processing analog differences in inputs across an entire network? Grossberg
      (1973) solved this noise-saturation dilemma using neurons that obey the membrane,
      or shunting, equations of neurophysiology interacting in recurrent and non
      recurrent on-center off-surround networks, and showed how different signal
      functions can influence the activity patterns that the network stores in short
      term memory. These results demonstrated that maintaining a balance between
      excitation and inhibition in a neural network is essential to process distributed
      patterns of inputs and signals without experiencing the catastrophies of noise or
      saturation. However, shunting on-center off-surround networks only guarantee that
      cell activities remain sensitive to the relative sizes of inputs and recurrent
      signals, but not that they will use the full dynamic range that each cell can
      support. Additional homeostatic plasticity mechanisms are needed to anchor the
      activities of networks to exploit their full dynamic range. This article shows
      how mechanisms of synaptic scaling can be incorporated within recurrent on-center
      off-surround networks in such a way that their pattern processing capabilities,
      including the ability to make winner-take-all decisions, is preserved. This model
      generalizes the synaptic scaling model of van Rossum, Bi, & Turrigiano (2000) for
      a single cell to a pattern-processing network of shunting cells that is capable
      of short-term memory storage, including a representation of how BDNF may
      homeostatically scale the strengths of excitatory and inhibitory synapses in
      opposite directions.

PMID- 21890321
TI  - Motion correction for cellular-resolution multi-photon fluorescence microscopy
      imaging of awake head-restrained mice using speed embedded HMM.
AB  - Multi-photon fluorescence microscopy (MFM) captures high-resolution fluorescence
      image sequences and can be used for the intact brain imaging of small animals.
      Recently, it has been extended from anesthetized and head-stabilized mice to
      awake and head-restrained ones for in vivo neurological study. In these
      applications, motion correction is an important pre-processing step since brain
      pulsation and body movement can cause motion artifact and prevent stable serial
      image acquisition at such high spatial resolution. This paper proposes a speed
      embedded Hidden Markov model (SEHMM) for motion correction in MFM imaging of
      awake head-restrained mice. The algorithm extends the traditional Hidden Markov
      model (HMM) method by embedding a motion prediction model to better estimate the
      state transition probability. The novelty of the method lies in using adaptive
      probability to estimate the linear motion, while the state-of-the-art method
      assumes that the highest probability is assigned to the case with no motion. In
      experiments we demonstrated that SEHMM is more accurate than the traditional HMM
      using both simulated and real MFM image sequences.

PMID- 21890322
TI  - Agreement between dietary and lifestyle guidelines for cancer prevention in
      population samples of Europeans and Mesoamericans.
AB  - OBJECTIVE: To assess concordance with selected individual guideline components of
      the 1997 World Cancer Research Fund/American Institute for Cancer Research
      (WCRF/AICR) diet and lifestyle recommendations to decrease cancer risk across
      four population samples. METHODS: The study was a prospectively designed survey
      examining concordance with individual-level guidelines of the WCRF/AICR
      recommendations using target criteria across sites. The status of concordance
      with eight dietary and eight lifestyle components subject to evaluation was
      described and compared across samples and with the target criteria. Population
      samples were from the Netherlands, Scotland, Mexico, and Guatemala. In total 3564
      male and female adults 18 to 70 y old were recruited in equal proportions by
      site. RESULTS: Overall concordance with the WCRF/AICR was low in all samples,
      with 28%, 63%, 77%, and 81% of subjects concordant with at least half of the
      selected recommendation components in the Netherlands, Scotland, Mexico, and
      Guatemala, respectively. Concordance was especially low for the recommendations
      to prefer fish or poultry, limit refined sugar consumption, and avoid eating
      charred food and especially high for the recommendations that dietary supplements
      are probably unnecessary, to avoid being underweight, and to consume
      predominately plant-based diets. CONCLUSION: A prospectively designed research
      instrument with exhaustive prior examination of operative criteria allows for the
      assessment of individual-level concordance or compliance with cancer-prevention
      guidelines. We postulate that efforts to maintain currently positive practices
      are the strategic priority in Central America, whereas efforts at behavioral
      reorientation are needed in Europe to bring the populations into concordance.

PMID- 21890323
TI  - Oral preoperative antioxidants in pancreatic surgery: a double-blind, randomized,
      clinical trial.
AB  - OBJECTIVE: Oxidative stress due to ischemia/reperfusion injury increases systemic
      inflammation and impairs immune defenses. Much interest has developed for the
      administration of antioxidant substrates in surgical patients. The purpose of
      this study was to perform a pilot evaluation of the impact of a carbohydrate-
      containing preconditioning oral nutritional supplement (pONS) enriched with
      glutamine, antioxidants, and green tea extract on postoperative oxidative stress.
      METHODS: We performed a double-blind placebo-controlled randomized clinical
      trial, involving 36 cancer patients undergoing pancreaticoduodenectomy. Patients
      were randomized to receive either pONS or placebo twice the day before surgery
      and once 3 hours before surgery. Total endogenous antioxidant capacity (TEAC),
      plasma levels of vitamin C, vitamin E, selenium, zinc, F2-isoprostanes, and C
      reactive protein were measured at baseline and on postoperative day (POD) 1, 3,
      and 7. RESULTS: At surgery, the mean gastric residual volume (mL) was 54.2 in the
      pONS group versus 51.3 in the placebo group (P = NS). On POD 1 plasma levels of
      vitamin C (P = 0.001), selenium (P = 0.07), and zinc (P = 0.06) were higher in
      the pONS group compared to placebo. TEAC was improved on POD 1, 3, and 7 in the
      pONS group compared to placebo (P = 0.01). No difference was found in plasma C
      reactive protein levels after surgery in both groups. CONCLUSIONS: Perioperative
      pONS administration positively affected plasma vitamin C levels and improved TEAC
      shortly after surgery, but did not reduce oxidative stress and systemic
      inflammation markers.

PMID- 21890324
TI  - Nutritional status and dietary habits of the population of the Calchaqui Valleys
      of Tucuman, Argentina.
AB  - OBJECTIVE: To assess the nutritional status and dietary habits of the adult
      population of the Calchaqui Valleys of Tucuman. METHODS: A cross-sectional
      nutritional survey that included one 24-h recall, a semiquantitative food
      frequency questionnaire, and anthropometric measurements was conducted in a
      representative sample of 113 adult participants. Pregnant and lactating women
      were excluded. Overweight and obesity were assessed according to body mass index,
      and the percentage of individuals with cardiovascular risk according to waist
      circumference and waist-to-hip circumference ratio was determined. Dietary habits
      were described according to the mean nutrient and food intakes of men and women.
      RESULTS: Means +/- standard deviations for total energy intake of men and women
      were 1856 +/- 859 and 1589 +/- 799 kcal/d, respectively. The average body mass
      indices of men and women were 26.8 and 26.7 kg/m(2), respectively. Thirty-seven
      percent of the population was overweight and 22.8% was obese, whereas 1.8% of the
      population was undernourished. Central adiposity was high (mean waist
      circumferences 99.8 and 87.3 cm in men and women, respectively). CONCLUSIONS:
      Despite the low average energy intake, the population under study showed a high
      prevalence of overweight and obesity and a high risk of cardiovascular disease
      according to the central adiposity values. These findings could be explained by
      the introduction of new high-energy foods and a sedentary lifestyle or the
      possibility that the biological characteristics of these individuals make them
      more predisposed to a rapid increase in adiposity.

PMID- 21890325
TI  - Plasma metalloproteinase levels and left ventricular remodeling in hypertrophic
      cardiomyopathy in patients with an identical mutation.
AB  - BACKGROUND AND PURPOSE: Although it has been reported that matrix
      metalloproteinases (MMPs) are associated with left ventricular (LV) remodeling in
      patients with hypertrophic cardiomyopathy (HCM), the impact of plasma MMP levels
      in patients with HCM is somewhat vague. METHODS AND SUBJECTS: Plasma levels of
      MMP-2, MMP-9, and clinical/echocardiographic findings were evaluated in 16 HCM
      patients with preserved LV ejection fraction (defined as LV ejection fraction
      more than 50%) caused by an identical frameshift mutation (S593fs: a one-base
      deletion of a thymidine at nucleotide 11,645) in the cardiac myosin-binding
      protein C gene. RESULTS: MMP-2 levels were inversely related to LV ejection
      fraction (r(2)=-37, p=0.01). MMP-9 levels were inversely related to LV end
      diastolic dimension (r(2)=-0.24, p=0.06) and positively related to the maximum LV
      wall thickness (r(2)=0.25, p=0.04). During follow-up period of 4.1 +/- 1.2 years,
      LV ejection fraction decreased from 68.5 +/- 7.4% to 64.9 +/- 9% (p=0.03). Among
      clinical, echocardiographic findings at baseline and levels of biomarkers, high
      MMP-9 levels were only related to the decrease of LV ejection fraction from
      baseline to follow-up (r(2)=0.39, p=0.009). CONCLUSIONS: MMP-2 levels are related
      to reduced LV systolic function in HCM patients with preserved LV ejection
      fraction caused by an identical cardiac myosin-binding protein C gene
      abnormality. On the other hand, MMP-9 levels are associated with small LV size
      and the degree of LV hypertrophy and related to the deterioration in LV systolic
      function during follow-up. These results suggest that MMPs are important in the
      process of LV remodeling in HCM.

PMID- 21890326
TI  - Visualization of coronary plaque in type 2 diabetes mellitus patients using a new
      40 MHz intravascular ultrasound imaging system.
AB  - BACKGROUND: Previous epidemiological studies demonstrated plaque vulnerability to
      be high in diabetic patients. iMap-intravascular ultrasound (IVUS) is a recently
      developed radiofrequency 40 MHz IVUS imaging system for tissue characterization.
      This study aimed to characterize coronary plaque in target lesions of diabetic
      patients using iMap-IVUS. METHODS: We studied 175 treated vessels in 146 patients
      with stable angina pectoris and analyzed plaque components of culprit lesions by
      iMAP-IVUS. Patients were divided into 2 groups: non-diabetic (non-DM: 112
      vessels, 93 patients) and diabetic (DM: 63 vessels, 53 patients). RESULTS: In
      gray-scale IVUS 2D analysis, there were no differences in IVUS parameters. In 3D
      analysis, the DM group tended to have a larger plaque volume (p=0.07) and plaque
      burden (p=0.10). At minimum lumen sites, the absolute lipidic and necrotic areas
      (0.84 +/- 0.44 mm(2) vs. 0.58 +/- 0.41 mm(2), p<0.001, and 2.42 +/- 1.65 mm(2)
      vs. 1.46 +/- 1.76 mm(2), p<0.001, respectively) and percent lipidic and necrotic
      areas were significantly greater in the DM than in the non-DM group (8.39 +/-
      3.38% vs. 5.25 +/- 2.30%, p<0.0001, and 23.65 +/- 11.54% vs. 12.99 +/- 10.71%,
      p<0.0001, respectively). In addition, the absolute lipidic and necrotic volumes
      (11.75 +/- 10.59 mm(3) vs. 8.18 +/- 6.24 mm(3), p<0.01, and 29.99 +/- 28.90 mm(3)
      vs. 19.44 +/- 19.35 mm(3), p<0.01, respectively) and percent lipidic and necrotic
      volumes were significantly greater in the DM than in the non-DM group (6.27 +/-
      1.92% vs. 5.13 +/- 1.82%, p<0.0001, and 16.54 +/- 7.56% vs. 12.08 +/- 6.05%,
      p<0.0001, respectively). CONCLUSION: Characterization of coronary plaque by iMAP
      IVUS in diabetic patients showed increased lipidic amount and necrotic plaque
      volume relative to subjects without DM.

PMID- 21890327
TI  - Scoring of late gadolinium enhancement in cardiac magnetic resonance imaging can
      predict cardiac events in patients with hypertrophic cardiomyopathy.
AB  - BACKGROUND: Late gadolinium enhancement (LGE) of cardiac magnetic resonance
      imaging (MRI) represents myocardial fibrosis and may be related to the clinical
      outcome of various heart diseases. This study evaluated the relationship between
      LGE and cardiac events in hypertrophic cardiomyopathy (HCM) using a new scoring
      method. METHODS AND RESULTS: This study retrospectively followed 46 HCM patients
      without heart failure symptoms for 3.8 +/- 1.8 years. Gadolinium-enhanced cardiac
      MRI was performed in all patients. Cardiac events including newly developed heart
      failure or ventricular tachyarrhythmia were evaluated during the follow-up
      period. We evaluated the predictive factors to identify the patients with cardiac
      events. None of the risk factors reported to be related to poor outcome or the
      existence of LGE alone could predict cardiac events, which might be due to the
      small number of subjects investigated in this study. A new scoring method for LGE
      positive areas (LGE score) was applied and higher LGE score can predict cardiac
      events in this study population. CONCLUSIONS: The proposed LGE score for cardiac
      MRI is considered to be a potentially valid method for assessing cardiac events
      in HCM patients.

PMID- 21890328
TI  - The putative functional rs1045881 marker of neurexin-1 in schizophrenia and
      clozapine response.
AB  - Neurexin-1 (NRXN1) modulates recruitment of NMDA receptors. Furthermore,
      clozapine reduces hyperactivity of NMDA receptors. Thus, regulation of the NRXN1
      gene may mediate the efficacy of clozapine at reducing cortical hyperactivity. We
      examined the putative functional SNP, rs1045881, for association with
      schizophrenia, and the potential role of this SNP in clozapine response. The
      rs1045881 variant was not significantly associated with schizophrenia (N=302 case
      control pairs), but with clozapine response (N=163; p=0.030). Baseline and BPRS
      scores after six months revealed a trend for rs1045881 genotype by treatment
      interaction (p=0.079). In the post hoc analysis, a significant association
      between BPRS negative symptoms score and genotype was observed (p=0.033). These
      results suggest that the rs1045881 NRXN1 polymorphism may influence clozapine
      response.

PMID- 21890329
TI  - Toxoplasma gondii antibody titers and history of suicide attempts in patients
      with schizophrenia.
AB  - Toxoplasma gondii (T. gondii) a widespread neurotropic parasite, has been
      previously associated with schizophrenia and more recently with suicidal
      behavior. However, no previous study has examined the association of T. gondii
      with suicidal behavior in schizophrenia patients. 950 individuals diagnosed with
      schizophrenia by SCID were recruited from the Munich area of Germany. Solid
      enzyme immunoassay methods were used to measure IgG plasma antibodies to T.
      gondii, other neurotropic pathogens and gliadin. Logistic regression models were
      developed to analyze the association of T. gondii seropositivity or serointensity
      with history of suicidal behavior. In those younger than the median age of the
      sample, 38, T. gondii serointensity was associated with history of suicidal
      behavior (p = 0.02), while in the older patients the relationship was not
      significant (p = 0.21). Seropositivity was also associated with history of
      suicide attempt in younger patients, odds ratio 1.59 (95% CI 1.06 to 2.40), p =
      0.03. Seropositivity for CMV (p = 0.22), HSV-1 (p = 0.36) and gliadin (p = 0.92)
      was not related to history of suicide attempt in the entire sample or any age
      subgroup. T. gondii serology might become, with interaction with vulnerability
      genes, a candidate biomarker for a subgroup of schizophrenia patients prone to
      attempting suicide.

PMID- 21890330
TI  - Silver resistance: an alarming public health concern?

PMID- 21890331
TI  - Incorporation and release behavior of amitriptylene in core-shell-corona type
      triblock copolymer micelles.
AB  - A cationic antidepressant drug, amitriptylene (AMT), was successfully
      incorporated into core-shell-corona micelles of poly[styrene-b-sodium 2
      (acrylamido)-2-methyl-1-propanesulfonate-b-ethylene oxide] (PS-b-PAMPS-b-PEO).
      Zeta-potential measurements revealed that both electrostatic and hydrophobic
      interactions contributed to the binding of the drug to the polymer. The AMT/PS-b
      PAMPS-b-PEO nanocomplexes were characterized by dynamic light scattering,
      scanning electron microscopy, and transmission electron microscopy. The
      hydrodynamic diameter of the AMT loaded nanocomplexes decreased from 80 to 40nm
      depending on the amount of the drug loaded on the polymer. This is attributed to
      the cancellation of the negative charge of the PAMPS group by the cationic drug.
      The AMT/PS-b-PAMPS-b-PEO nanocomplexes were stable in aqueous solution exhibiting
      no aggregation or no precipitation for several months. Release of the AMT from
      the nanocomplexes was investigated in vitro in salt-free and 0.1M NaCl solutions.
      The drug was released faster in the 0.1M NaCl solution than in the salt-free
      solution. This is due to the shielding effect of the salt on the electrostatic
      interaction. However, in both cases, the drug release mainly occurs by the
      Fickian diffusion mechanism.

PMID- 21890332
TI  - Preparation of highly dispersible and tumor-accumulative, iron oxide
      nanoparticles Multi-point anchoring of PEG-b-poly(4-vinylbenzylphosphonate)
      improves performance significantly.
AB  - This paper describes the preparation of iron oxide nanoparticles, surface of
      which was coated with extremely high immobilization stability and relatively
      higher density of poly(ethylene glycol) (PEG), which are referred to as PEG
      protected iron oxide nanoparticles (PEG-PIONs). The PEG-PIONs were obtained
      through alkali coprecipitation of iron salts in the presence of the PEG-poly(4
      vinylbenzylphosphonate) block copolymer (PEG-b-PVBP). In this system, PEG-b-PVBP
      served as a surface coating that was bound to the iron oxide surface via
      multipoint anchoring of the phosphonate groups in the PVBP segment of PEG-b-PVBP.
      The binding of PEG-b-PVBP onto the iron oxide nanoparticle surface and the
      subsequent formation of a PEG brush layer were proved by FT-IR, zeta potential,
      and thermogravimetric measurements. The surface PEG-chain density of the PEG
      PIONs varied depending on the [PEG-b-PVBP]/[iron salts] feed-weight ratio in the
      coprecipitation reaction. PEG-PIONs prepared at an optimal feed-weight ratio in
      this study showed a high surface PEG-chain surface density (~0.8 chainsnm(-2))
      and small hydrodynamic diameter (<50 nm). Furthermore, these PEG-PIONs could be
      dispersed in phosphate-buffered saline (PBS) that contains 10% serum without any
      change in their hydrodynamic diameters over a period of one week, indicating that
      PEG-PIONs would provide high dispersion stability under in vivo physiological
      conditions as well as excellent anti-biofouling properties. In fact we have
      confirmed the prolong blood circulation time and facilitate tumor accumulation
      (more than 15% IDg(-1) tumor) of PEG-PIONs without the aid of any target ligand
      in mouse tumor models. The majority of the PEG-PIONs accumulated in the tumor by
      96 h after administration, whereas those in normal tissues were smoothly
      eliminated by 96 h, proving the enhancement of tumor selectivity in the PEG-PION
      localization. The results obtained here strongly suggest that originally
      synthesized PEG-b-PVBP, having multipoint anchoring character by the phosphonate
      groups, is rational design for improvement in nanoparticle as in vivo
      application. Two major points, viz., extremely stable anchoring character and
      dense PEG chains tethered on the nanoparticle surface, worked simultaneously to
      become PEG-PIONs as an ideal biomedical devices intact for prolonged periods in
      harsh biological environments.

PMID- 21890333
TI  - Structural and ultrastructural differentiation of the thyroid gland during
      embryogenesis in the grass snake Natrix natrix L. (Lepidosauria, Serpentes).
AB  - The differentiation of the thyroid primordium of reptilian species is poorly
      understood. The present study reports on structural and ultrastructural studies
      of the developing thyroid gland in embryos of the grass snake Natrix natrix L. At
      the time of oviposition, the thyroid primordium occupied its final position in
      the embryos. Throughout developmental stages I-IV, the undifferentiated thyroid
      primordium contained cellular cords, and the plasma membranes of adjacent cells
      formed junctional complexes. Subsequently, the first follicular lumens started to
      form. The follicular lumens were of intracellular origin, as in other vertebrate
      species, but the mechanism of their formation is as yet unclear. At developmental
      stages V-VI, the thyroid anlage was composed of small follicles with lumens and
      cellular cords. Cells of the thyroid primordium divided, and follicles were
      filled with a granular substance. At developmental stage VI, the cells
      surrounding the follicular lumen were polarized, the apical cytoplasm contained
      dark granules and the Golgi complex and the rough endoplasmic reticulum (RER)
      developed gradually. Resorption of the colloid began at developmental stage VIII.
      At the end of this stage, the embryonic thyroid gland was surrounded by a
      definitive capsule. During developmental stages IX-X, the follicular cells
      contained granules and vesicles of different sizes and electron densities and a
      well-developed Golgi apparatus and RER. At developmental stage XI, most follicles
      were outlined by squamous epithelial cells and presented wide lumens filled with
      a light colloid. The Golgi complex and RER showed changes in their morphology
      indicating a decrease in the activity of the thyroid gland. At developmental
      stage XII, the activity of the embryonic thyroid gradually increased, and at the
      time of hatching, it exhibited the features of a fully active gland.

PMID- 21890334
TI  - Determination of bioactive markers in Cleome droserifolia using cell-based
      bioassays for antidiabetic activity and isolation of two novel active compounds.
AB  - The antidiabetic activities of the aqueous (AqEx) and ethanolic (AlEx) extracts
      of Cleome droserifolia (Forssk.) Del., were tested in cultured C2C12 skeletal
      muscle cells and 3T3-L1 adipocytes. An 18-h treatment with the AqEx increased
      basal glucose uptake by 33% [insulin equivalent (IE)=1.3+/-0.04] in muscle cells
      comparable to a 25.5% increase caused by 100 nM insulin (IE=1+/-0.03).
      Fractionation of the tested AqEx yielded hexane (HxFr), chloroform (ClFr) and
      ethyl acetate (EtFr) fractions which exerted 38, 52 and 35% increase in the
      glucose uptake corresponding to an IE of 1.5+/-0.06, 2.0+/-0.04 and 1.4+/-0.04,
      respectively. Only the ClFr and EtFr accelerated the triglyceride accumulation
      [rosiglitazone equivalent (RE) was 0.9+/-0.13 and 0.63+/-0.12, respectively] in
      pre-adipocytes undergoing differentiation comparably with 10 MUM rosiglitazone.
      Six terpenoids (C1-C6) and three flavonol glycosides (F1-F3) were isolated from
      the active ClFr and EtFr, respectively, and identified. C5, C2 and C4 had an IE
      of 0.86+/-0.05, 1.01+/-0.04 and 0.9+/-0.08, while F1, F2 and F3 gave an IE of
      1.3+/-0.05, 2.3+/-0.05 and 2.0+/-0.04, respectively. We could conclude that the
      reported antihyperglycemic activity of Cleome droserifolia is attributed to
      significant insulin-like effects in peripheral tissues, and that compounds F2 and
      F3, being highly active, could be used as bioactive markers to standardize the C.
      droserifolia herbal extract.

PMID- 21890335
TI  - Efficacy of a fixed combination of ciclesonide and formoterol: the EXCITED-study.
AB  - Recommended treatment for moderate to severe asthma is the combination of an
      inhaled corticosteroid and a long-acting beta2-agonist. The present study was
      designed to evaluate the efficacy of a newly developed fixed combination of
      ciclesonide and formoterol in comparison to the marketed fixed combination of
      fluticasone and salmeterol in patients with moderate asthma. This was a phase II,
      multi-centre, randomized, parallel-group, double-blind, double-dummy study. After
      a 2-week run-in period, 160 patients with moderate asthma were randomized to a 6
      week treatment with ciclesonide/formoterol 320/9 MUg bid (CIC/F) or fluticasone
      propionate/salmeterol 250/50 MUg bid (FP/S), both delivered as powder
      formulations. The primary outcome FEV1 increased during treatment by 0.356 L in
      the CIC/F group and by 0.288 L in the FP/S group (p < 0.0001). The increases were
      statistically significant and clinically relevant. The between-treatment analysis
      demonstrated non-inferiority of CIC/F to FP/S treatment (p < 0.0001). A
      significant improvement from baseline in lung function, symptom score and rescue
      medication use was observed in both groups at all time points. No differences
      were observed between treatments in the frequency of adverse events and overnight
      urinary cortisol/creatinine ratio. The studied fixed combination of
      ciclesonide/formoterol is not inferior to the marketed fixed combination of
      fluticasone/salmeterol in terms of efficacy and tolerability.

PMID- 21890337
TI  - Mechanotransduction at cadherin-mediated adhesions.
AB  - Cell-to-cell junctions are crucial mechanical and signaling hubs that connect
      cells within tissues and probe the mechanics of the surrounding environment.
      Although the capacity of cell-to-extracellular-matrix (ECM) adhesions to sense
      matrix mechanics and proportionally modify cell functions is well established,
      cell-cell adhesions only recently emerged as a new class of force sensors. This
      finding exposes new pathways through which force can instruct cell functions.
      This review highlights recent findings, which demonstrate that protein complexes
      associated with classical cadherins, the principal architectural proteins at cell
      cell junctions in all soft tissues, are mechanosensors. We further discuss the
      current understanding of the rudiments of a cadherin-based mechanosensing and
      transduction pathway, which is distinct from the force sensing machinery of cell
      ECM adhesions.

PMID- 21890336
TI  - Clinical characteristics and possible phenotypes of an adult severe asthma
      population.
AB  - BACKGROUND: Currently, there are no studies of well-characterized severe
      asthmatics in Brazil. We aimed to study a population of severe treated asthmatics
      still uncontrolled to characterize them and define possible phenotypes. METHODS:
      Descriptive cross-sectional outpatient study of severe asthmatics, evaluating
      functional and inflammatory markers, health-related quality of life, anxiety and
      depression symptoms, clinical control status, and characteristics related to
      atopy, age of asthma onset, induced sputum eosinophil levels, and airflow
      limitation. We also grouped the subgroups characteristics to identify phenotypes.
      The study is registered on ClinicalTrial.gov NCT 01089322. RESULTS: From 128
      eligible patients with severe/uncontrolled asthma, 74 fulfilled the inclusion
      criteria. The cohort was comprised of 85% women, frequently with a body mass
      index higher than 31 kg m(-2), atopy (60%), early-onset disease (50%), sputum
      eosinophilia (80%), comorbidities, and reduced quality of life. Nonatopics had
      significant higher asthma onset (19 y.a.) and twice level of induced sputum
      eosinophil. Late-onset patients had significantly less atopy (57%) and higher
      levels of induced sputum eosinophils. Non-eosinophilics had lower levels of
      inflammatory markers. Patients with airflow limitation had more intensive care
      unit admissions (56%) and 1.5 times more airway resistance. Subgroups
      characteristics identified a priori four well-characterized phenotypes, with 55%
      presenting sputum eosinophilia. CONCLUSION: Our data emphasize the high burden of
      disease, the persistence of inflammation and the existence of clinical possible
      phenotypes population sharing common features with published cohorts. Despite the
      necessity of further investigation into pathogenic mechanisms, this study with
      clinically difficult patient group may help to improve future asthma care.

PMID- 21890338
TI  - Partnerships and communities in English drug policy: the challenge of
      deprivation.
AB  - BACKGROUND: From the mid-1990s, UK governments developed partnerships to tackle
      drugs nationally and locally. Over time, increased resources focused on
      communities and localities in greatest need. This reflected growing awareness of
      the concentration of problems in deprived areas, with social and spatial
      segregation being a feature of post-industrial urban areas. METHODS: A review of
      English drug policy since the 1990s, drawing on:- analysis of documents; a review
      of sociological studies; an illustrative case-study of one northern town;
      interviews with local policy players; statistical analysis of key indicators with
      some of these data presented using Geographical Information System (GIS) mapping.
      RESULTS: In-depth sociological studies demonstrate interconnections between
      historical patterns, socio-economic change, cultural complexity, deprivation,
      limited opportunities and illicit drugs. At local level, there are links between
      concentrated multiple deprivation, poor health, acquisitive crime and problematic
      drug use. Partnership policies, encouraged by the provision of ring-fenced funds,
      have been effective in containing problems. Underlying issues of inequality are
      however neglected in political debates. The article argues that post-industrial
      towns and cities are characterised by an increase in problems related to poverty
      and drugs. Both the real shape and perceptions of what is the problem change over
      time. In England, the profile of the problem drug user was described in a number
      of sociological studies conducted from the 1980s onwards. Key features were the
      concentration of problems in certain social groups (such as the poorly educated
      or unemployed) and in certain areas (inner cities or outer estates). Responding
      to rising public concern, national drug strategies developed and the New Labour
      Government after 1997 prioritised the issue of drugs, directing increased
      resources to drug treatment with tight control over the use of these new monies
      through target setting and measurement of performance. The emphasis was on the
      most dangerous drugs and most disadvantaged areas. CONCLUSION: There is local
      variation in the pattern of problems and in implementation of national policies.
      In UK after 1997, New Labour policy aimed to promote a fair and cost-effective
      distribution of resources and improved availability and quality of treatment
      services and local policing. Tensions appeared between the drive to meet national
      targets and local perceptions of need. Ideas of localism, promoting market
      solutions and flexibility in provision, are now gaining ground in English social
      policy with the arrival of a Coalition (Conservative/Liberal Democrat)
      Government. These, together with an emphasis on abstinence and recovery, raise
      questions about the future adequacy of (a) attention to marginalised problems and
      stigmatised groups and (b) the distribution of resources in a context of severe
      fiscal restraint.

PMID- 21890339
TI  - Toxin detection by Si photosensitive biosensors with a new measurement scheme.
AB  - We propose a new type of photosensitive biosensor with a CMOS compatible Si
      photodiode integrated circuit, for the high-sensitive detection of small
      mycotoxin molecules requiring competitive assay approach. In this work, a
      photodiode is connected to the gate of a field effect transistor (FET) so that
      the open circuit voltage (V(OC)) of the illuminated photodiode is transferred
      into the drain/source current (I(DS)) of the FET. The sensing scheme employs
      competitive binding of toxin molecules (within the sample solution) and toxin-BSA
      conjugates (immobilized on the photodiode surface) with Au-nanoparticle-labeled
      antibodies, followed by silver enhancement to generate opaque structures on the
      photodiode surface. By utilizing the non-linear dependence of the V(OC) on the
      light intensity, we can maintain a sufficiently high signal resolution at low
      toxin concentrations (with most of the incident light blocked) for the
      competitive assay. By monitoring the I(DS) of the FET whose gate is driven by the
      V(OC), quantitative detection of Aflatoxin B1 has been achieved in the range of 0
      15ppb.

PMID- 21890340
TI  - Integrating photobiological hydrogen production with dye-metal bioremoval from
      simulated textile wastewater.
AB  - The study reports production of hydrogen in photobioreactors with free (PBR(Fr))
      and immobilized (PBR(Imm)) Nostoc biomass at enhanced and sustained rates. Before
      running the photobioreactors, effects of different immobilization matrices and
      cyanobacterial dose on hydrogen production were studied in batch mode. As
      hydrogen production in the PBRs declined spent biomass from the photobioreactors
      were collected and utilized further for column biosorption of highly toxic dyes
      (Reactive Red 198+Crystal Violet) and metals (hexavalent chromium and bivalent
      cobalt) from simulated textile wastewater. Breakthrough time, adsorption capacity
      and exhaustion time of the biosorption column were studied. The photobioreactors
      with free and immobilized cyanobacterium produced hydrogen at average rates of
      101 and 151 MUmol/h/mg Chl a, respectively over 15 days, while the adsorption
      capacity of the spent biomass was up to 1.4 and 0.23 mg/g for metals and 15 and
      1.75 mg/g for the dyes, respectively in continuous column mode.

PMID- 21890341
TI  - Enzymatic synthesis of sialic acid derivative by immobilized lipase from Candida
      antarctica.
AB  - The effects of important reaction parameters on the enhancement of sialic acid
      derivative lipophilic properties through the lipase-catalyzed esterification of N
      acetyl neuraminic acid methyl ester are investigated in this study. It is found
      that the lipase Novozym 435 from Candida antarctica is particularly useful in the
      preparation of sialic acid methyl ester monononanoate (SAMEMN). The optimum
      temperature for the SAMEMN synthesis reaction using Novozym 435 is 60 degrees C,
      and nonanoic anhydride is found to be the best substrate among all acyl donors.
      The Novozym 435-catalyzed esterification of N-acetyl neuraminic acid methyl ester
      gave a maximum yield of 87.7% after 6h in acetonitrile at 60 degrees C. Because
      the novel method developed is simple, yet effective, it could potentially be used
      industrially for the production of sialic acid derivatives.

PMID- 21890342
TI  - Ethanol production from selected lignocellulosic hydrolysates by genome shuffled
      strains of Scheffersomyces stipitis.
AB  - Two genome-shuffled Scheffersomyces stipitis strains, GS301 and GS302, exhibiting
      improved tolerance to hardwood spent sulphite liquor, were tested for growth and
      fermentation performance on three wood hydrolysates: (a) steam-pretreated
      enzymatically hydrolyzed poplar hydrolysate from Mascoma Canada, (b) steam
      pretreated poplar hydrolysate from University of British Columbia Forest Products
      Biotechnology Laboratory, and (c) mixed hardwoods pre-hydrolysate from
      FPInnovations (FPI). In the FPI hydrolysate, the wild type (WT) died off within
      25 h, while GS301 and GS302 survived beyond 100 h. In fermentation tests, GS301
      and GS302 completely utilized glucose and xylose in each hydrolysate and produced
      0.39-1.4% (w/v) ethanol. In contrast, the WT did not utilize or poorly utilized
      glucose and xylose and produced non-detectable to trace amounts of ethanol. The
      results demonstrated cross tolerance of the mutants to inhibitors in three
      different wood hydrolysates and reinforced the utility of mating-based genome
      shuffling approach in industrial yeast strain improvement.

PMID- 21890343
TI  - Anaerobic digestion of thin stillage for energy recovery and water reuse in corn
      ethanol plants.
AB  - Recycling of anaerobically-digested thin stillage within a corn-ethanol plant may
      result in the accumulation of nutrients of environmental concern in animal feed
      coproducts and inhibitory organic materials in the fermentation tank. Our focus
      is on anaerobic digestion of treated (centrifugation and lime addition) thin
      stillage. Suitability of digestate from anaerobic treatment for reuse as process
      water was also investigated. Experiments conducted at various inoculum-to
      substrate ratios (ISRs) revealed that alkalinity is a critical parameter limiting
      digestibility of thin stillage. An ISR level of 2 appeared optimal based on high
      biogas production level (763 mL biogas/g volatile solids added) and organic
      matter removal (80.6% COD removal). The digester supernatant at this ISR level
      was found to contain both organic and inorganic constituents at levels that would
      cause no inhibition to ethanol fermentation. Anaerobic digestion of treated-thin
      stillage can be expected to improve the water and energy efficiencies of dry
      grind corn-ethanol plants.

PMID- 21890344
TI  - Biogas production from supernatant of hydrothermally treated municipal sludge by
      upflow anaerobic sludge blanket reactor.
AB  - The supernatant of hydrothermally treated sludge was treated by an upflow
      anaerobic sludge blanket (UASB) reactor for a 550-days running test. The
      hydrothermal parameter was 170 degrees C for 60 min. An mesophilic 8.6L UASB
      reactor was seeded with floc sludge. The final organic loading rate (OLR) could
      reach 18 kg COD/m(3)d. At the initial stage running for 189 days, the feed
      supernatant was diluted, and the OLR reached 11 kg COD/m(3)d. After 218 days, the
      reactor achieved a high OLR, and the supernatant was pumped into the reactor
      without dilution. The influent COD fluctuated from 20,000 to 30,000 mg/L and the
      COD removal rate remained at approximately 70%. After 150 days, granular sludge
      was observed. The energy balance calculation show that heating 1.0 kg sludge
      needs 0.34 MJ of energy, whereas biogas energy from the supernatant of the heated
      sludge is 0.43MJ.

PMID- 21890346
TI  - A simple and rapid harvesting method for microalgae by in situ magnetic
      separation.
AB  - A simple and rapid harvesting method by in situ magnetic separation with naked
      Fe(3)O(4) nanoparticles has been developed for the microalgal recovery of
      Botryococcus braunii and Chlorella ellipsoidea. After adding the magnetic
      particles to the microalgal culture broth, the microalgal cells were adsorbed and
      then separated by an external magnetic field. The maximal recovery efficiency
      reached more than 98% for both microalgae at a stirring speed of 120 r/min within
      1 min, and the maximal adsorption capacity of these Fe(3)O(4) nanoparticles
      reached 55.9 mg-dry biomass/mg-particles for B. braunii and 5.83 mg-dry
      biomass/mg-particles for C. ellipsoidea. Appropriate pH value and high
      nanoparticle dose were favorable to the microalgae recovery, and the adsorption
      mechanism between the naked Fe(3)O(4) nanoparticles and the microalgal cells was
      mainly due to the electrostatic attraction. The developed in situ magnetic
      separation technology provides a great potential for saving time and energy
      associated with improving microalgal harvesting.

PMID- 21890345
TI  - Long-term starvation and subsequent reactivation of a high-rate partial
      nitrification activated sludge pilot plant.
AB  - The starvation process of a high-rate partial nitrification system during 30 days
      and its controlled recovery were studied in an activated sludge pilot plant. Four
      ammonium-starved reactors under anoxic, aerobic and two different alternating
      aerobic/anoxic conditions were evaluated. The highest and the lowest decay rates
      of ammonia oxidizing bacteria (AOB) were obtained under full aerobic (0.24 d(-1))
      and full anoxic (0.11 d(-1)) conditions, respectively. The evolution of biomass
      activity correlated well with the AOB quantification using FISH technique. AOB
      fractions lower than 1% were measured in the four reactors after 23 days of
      starvation. The recovery of the system was achieved in only 5 days using a
      nitrogen loading rate (NLR) control loop, obtaining the same conditions than
      before the long-term starvation period with a NLR of 1.2 g N L(-1)d(-1) and 98%
      of nitrite accumulation in the effluent.

PMID- 21890347
TI  - Inactivation of Amphidinium sp. in ballast waters using UV/Ag-TiO2+O3 advanced
      oxidation treatment.
AB  - Ballast water poses a biological threat to the world's waterways by transferring
      aquatic species from one body of water to another. This study investigates the
      use of combined ultraviolet (UV)/Ag-TiO(2)+ozone (O(3)) processes for treating
      ballast water using Amphidinium sp. as an indicator microorganism. Sufficient
      Amphidinium sp. cells in ballast waters can be inactivated using O(3) alone, UV
      irradiation alone (with or without an Ag-TiO(2) coating), and combined
      treatments. For the low inactivation ratio (<40%) regime, the effects of
      ozonation and photocatalysis were observed to be cumulative. The combined UV/Ag
      TiO(2)+O(3) treatment produced excess hydroxyl radicals and total residual
      oxidants (TROs), and readily damaged cell membranes to release intracellular
      substances. The comparison tests revealed that the combined treatments
      synergistically inactivate Escherichia coli in ballast waters. However, the
      combined process did not synergistically inactivate Amphidinium sp. cells.
      Inactivating different aqua species in ballast waters needs distinct treatment
      methods and dosages.

PMID- 21890348
TI  - Synergistic action of azoreductase and laccase leads to maximal decolourization
      and detoxification of model dye-containing wastewaters.
AB  - The azoreductase PpAzoR from Pseudomonas putida shows a broader specificity for
      decolourization of azo dyes than CotA-laccase from Bacillus subtilis. However,
      the final products of PpAzoR activity exhibited in most cases a 2 to 3-fold
      higher toxicity than intact dyes themselves. We show that addition of CotA
      laccase to PpAzoR reaction mixtures lead to a significant drop in the final
      toxicity. A sequential enzymatic process was validated through the use of 18
      representative azo dyes and three model wastewaters that mimic real dye
      containing effluents. A heterologous Escherichia coli strain was successfully
      constructed co-expressing the genes coding for both PpAzoR and CotA. Whole-cell
      assays of recombinant strain for the treatment of model dye wastewater resulted
      in decolourization levels above 80% and detoxification levels up to 50%. The high
      attributes of this strain, make it a promising candidate for the biological
      treatment of industrial dye containing effluents.

PMID- 21890349
TI  - Ultrasound-assisted extraction of flaxseed oil using immobilized enzymes.
AB  - An aqueous enzymatic process assisted by ultrasound extraction (AEP-UE) was
      applied to the extraction of oil from flaxseed (Linum usitatissimum L.). The
      highest oil recovery of 68.1% was obtained when ground flaxseed was incubated
      with 130 U/g of cellulase, pectinase, and hemicellulase for 12h, at 45 degrees C
      and pH 5.0. The IC(50) values of oil obtained by AEP-UE and organic solvent
      extraction (OSE), as measured by DPPH scavenging activity essay, were 2.27 mg/mL
      and 3.31 mg/mL. The AEP-UE-derived oil had a 1.5% higher content of unsaturated
      fatty acids than the OSE-derived oil. AEP-UE is therefore a promising
      environmentally friendly method for large-scale preparation of flaxseed oil.

PMID- 21890350
TI  - Preparatory production of quercetin-3-beta-D-glucopyranoside using alkali
      tolerant thermostable alpha-L-rhamnosidase from Aspergillus terreus.
AB  - Extensive screening for a robust producer of alpha-L-rhamnosidase activity from
      well-defined strains of filamentous fungi, including multifactorial optimization
      (inducers, cultivation conditions) was accomplished. Enzyme production of the
      optimal producer Aspergillus terreus (non-toxigenic) was scaled up to 50L. alpha
      L-Rhamnosidase, which was fully characterized, proved to be thermo- and alkali
      tolerant, thus enabling effective operation at 70 degrees C and pH 8.0. These
      conditions allow for a very high substrate (rutin) load up to 100-300 g/L, thus
      enabling very high volumetric productivity of the reaction product quercetin-3
      beta-D-glucopyranoside (isoquercitrin). Here, a novel concept of "immobilised
      substrate" is used. Isoquercitrin is a highly effective and biocompatible
      antioxidant with strong anti-inflammatory activities. Rutin biotransformation was
      optimized and scaled up to ca 10 kg production and thus the robustness of the
      large-scale production was demonstrated. Isoquercitrin can be produced to a very
      high purity (98%) in multikilogram amounts, without any quercetin and directly
      applicable in nutraceuticals.

PMID- 21890351
TI  - Evaluation of the potential role of the macroalga Laminaria japonica for
      alleviating coastal eutrophication.
AB  - The rapid development of human activities has caused serious eutrophication of
      coastal waters in China in the recent decades. The study of the biofiltration
      capacity of Laminaria japonica under laboratory conditions showed a significant
      nutrient uptake. After 36 h of incubation, around 42%, 46%, 44% of N and 45%,
      42%, 35% of P were removed from three gradients of medium concentrations,
      respectively. In the conditions of different ratios of N/P and NO(3)-N/NH(4)-N,
      the optimum N/P ratio for nutrient uptake was 7.4 and L. japonica preferred NO(3)
      N rather than NH(4)-N as nitrogen source. Temperature and irradiance affected
      uptake rates significantly. The maximal N uptake rate appeared at 10 degrees C
      and 18 MUmol photons m(-2)s(-1) and the maximal P uptake rate was found at 15
      degrees C and 144 MUmol photons m(-2)s(-1). Moreover, further studies were needed
      to investigate the bioremediation potential of L. japonica in the open sea.

PMID- 21890352
TI  - Characterization of the steam-exploded spent Shiitake mushroom medium and its
      efficient conversion to ethanol.
AB  - Spent Shiitake mushroom medium was subjected to steam explosion followed by
      simultaneous saccharification and fermentation (SSF) using Meicelase and
      Saccahromyces cerevisiae AM12. Water extraction of the medium exposed to steam at
      20 atm for 5 min enhanced the saccharification rate by about 20% compared to
      steam-exploded medium before water extraction and resulted in the production of
      23.8 g/l ethanol from a substrate concentration of 100g/l. This corresponded to
      87.6% of the theoretical ethanol yield, i.e., 15.9 g ethanol was obtained from
      100g of spent Shiitake mushroom medium. Spent Shiitake mushroom medium subjected
      to steam explosion and then water extraction appears to be a candidate for
      efficient bioconversion to ethanol.

PMID- 21890353
TI  - Nitrogen removal in moving bed sequencing batch reactor using polyurethane foam
      cubes of various sizes as carrier materials.
AB  - The performance of moving bed sequencing batch reactors (MBSBRs) added with 8 %
      (v/v) of polyurethane (PU) foam cubes as carrier media in nitrogen removal was
      investigated in treating low COD/N wastewater. The results indicate that MBSBR
      with 8-mL cubes achieved the highest total nitrogen (TN) removal efficiency of
      37% during the aeration period, followed by 31%, 24% and 19 % for MBSBRs with 27
      , 64- and 125-mL cubes, respectively. The increased TN removal in MBSBRs was
      mainly due to simultaneous nitrification and denitrification (SND) process which
      was verified by batch studies. The relatively lower TN removal in MBSBR with
      larger PU foam cubes was attributed to the observation that larger PU foam cubes
      were not fully attached by biomass. Higher concentrations of 8-mL PU foam cubes
      in batch reactors yielded higher TN removal.

PMID- 21890354
TI  - Carbon mineralization and distribution of nutrients within different particle
      size fractions of commercially produced olive mill pomace.
AB  - Composting is a realistic option for disposal of olive mill pomace (OMP) by
      making it suitable as a soil amendment for organic farming. The chemical and
      physical characteristics and contribution of particle-size fractions to total
      nutrients and carbon mineralization of seven commercial composts of OMP (COMP)
      were investigated. Higher proportions of manure, co-composted with OMP, reduced
      the organic matter (OM), total carbon and C:N ratio of the product, but increased
      the content of nutrients and fine particles. The fine particles had higher
      nutrient contents, but less OM and carbon and, unlike larger particles, did not
      exhibit any phytotoxicity. Less than 1.5% of added carbon was mineralized in
      whole compost, but a lower rate was found with larger particles. Separation of
      COMP by particle size fractionation and application as a soil conditioner is
      recommended for better optimization of COMP with the <1mm fraction providing the
      higher quality compost.

PMID- 21890355
TI  - Localization of GroEL determined by in vivo incorporation of a fluorescent amino
      acid.
AB  - The molecular chaperone GroEL is required for bacterial growth under all
      conditions, mediating folding assistance, via its central cavity, to a diverse
      set of cytosolic proteins; yet the subcellular localization of GroEL remains
      unresolved. An earlier study, using antibody probing of fixed Escherichia coli
      cells, indicated colocalization with the cell division protein FtsZ at the
      cleavage furrow, while a second E. coli study of fixed cells indicated more even
      distribution throughout the cytoplasm. Here, for the first time, we have examined
      the spatial distribution of GroEL in living cells using incorporation of a
      fluorescent unnatural amino acid into the chaperone. Fluorescence microscopy
      indicated that GroEL is diffusely distributed, both under normal and stress
      conditions. Importantly, the present procedure uses a small, fluorescent
      unnatural amino acid to visualize GroEL in vivo, avoiding the steric demands of a
      fluorescent protein fusion, which compromises proper GroEL assembly. Further,
      this unnatural amino acid incorporation avoids artifacts that can occur with
      fixation and antibody staining.

PMID- 21890356
TI  - Conformationally constrained farnesoid X receptor (FXR) agonists: alternative
      replacements of the stilbene.
AB  - To further explore the optimum placement of the acid moiety in conformationally
      constrained analogs of GW 4064 1a, a series of stilbene replacements were
      prepared. The benzothiophene 1f and the indole 1g display the optimal orientation
      of the carboxylate for enhanced FXR agonist potency.

PMID- 21890357
TI  - Substitution of the GalNAc-alpha-O-Thr11 residue in drosocin with O-linked glyco
      peptoid residue: effect on antibacterial activity and conformational change.
AB  - One of the obvious disadvantages of natural peptides is their liability to
      proteases. Among the several solutions for this issue, peptoids or oligomers of N
      substituted glycine have emerged as a promising tool that may enhance the
      stability of proteolysis-susceptible natural peptides. We have synthesized the
      drosocin and its glyco-peptoid analogues linked O-GalNAc at the Thr(11) residue.
      One of our glyco-peptoid analogues showed an increased antibacterial activity by
      the modification of the Thr(11) residue with glyco-peptoid. Structure-activity
      relationship studies revealed that the antibacterial activity by glyco-peptoid
      drosocin requires three key elements: free hydroxyl group on the carbohydrate
      moiety, gamma-methyl group of the Thr(11) residue derivative and (S)
      configuration over (R)-configuration.

PMID- 21890358
TI  - Isomeric acetoxy analogs of celecoxib and their evaluation as cyclooxygenase
      inhibitors.
AB  - A group of celecoxib analogs having a SO(2)NH(2) (9a-f), or SO(2)Me (12a-f), COX
      2 pharmacophore at the para-position of the N-1 phenyl ring in conjunction with a
      C-5 phenyl ring having a variety of substituents (4-, 3-, 2-OAc; 4-Me,2-OAc, 4
      Me,3-OAc, 4-F,2-OAc) was synthesized for evaluation as cyclooxygenase (COX)
      inhibitors of the COX-1/COX-2 isozymes. Within this group of compounds, 1-(4
      aminosulfonylphenyl)-3-trifluoromethyl-5-(2-acetoxy-4-fluorophenyl)pyrazole (9f)
      emerged as the most potent (COX-1 IC(50)=0.7 MUM; COX-2 IC(50)=0.015 MUM) and
      selective (COX-2 selectivity index=47) inhibitor agent that exhibited good anti
      inflammatory activity (ED(50)=42.3mg/kg) which was lower than the reference drug
      celecoxib (ED(50)=10.8 mg/kg), but greater than ibuprofen (ED(50)=67.4 mg/kg) and
      aspirin (ED(50)=128.7 mg/kg). Molecular modeling studies for 9f showed that the
      SO(2)NH(2) group assumes a position within the secondary pocket of the COX-2
      active site wherein the SO(2)NH(2) oxygen atom is hydrogen bonded to the H90
      residue (2.90A), the SO(2)NH(2) nitrogen atom forms a hydrogen bond with L352
      (N?O=2.80A), and the acetyl group is positioned in the vicinity of the S530
      residue where the acetyl oxygen atom undergoes hydrogen bonding to L531 (2.99A).

PMID- 21890359
TI  - Microwave assisted synthesis and antimicrobial evaluation of new fused pyran
      derivatives bearing 2-morpholinoquinoline nucleus.
AB  - A new series of fused pyran derivatives 5a-x bearing 2-morpholinoquinoline
      nucleus has been synthesized under microwave irradiation by a reaction of 2
      morpholinoquinoline-3-carbaldehyde 2a-c, malononitrile 3 and compounds 4a-h in
      presence of NaOH as basic catalyst. All the compounds were screened against three
      Gram positive bacteria (Streptococcus pneumoniae, Clostridium tetani, Bacillus
      subtilis), three Gram negative bacteria (Salmonella typhi, Vibrio cholerae,
      Escherichia coli) and two fungi (Aspergillus fumigatus, Candida albicans) using
      broth microdilution MIC (Minimum Inhibitory Concentration) method. Of the
      compounds studied, compounds 5b, 5f, 5k, 5m, 5q, 5s and 5v have found to be most
      efficient members of the series.

PMID- 21890360
TI  - Breast reconstruction: a quality measure for breast cancer care?
AB  - Parallel to its life-threatening nature, breast cancer can affect physical
      integrity, having a psychosocial impact on patients. Determining the optimal
      proportion of patients who should undergo breast reconstruction after cancer
      surgery represents a complex task. What seems to be unquestionable is that the
      ability to offer reconstruction and a wide range of surgical options plays an
      important role in current breast cancer management. The multidisciplinary
      approach is a paramount aspect not only for a successful oncologic treatment, but
      also for improving patient quality of life.

PMID- 21890361
TI  - Kinematic strategies for walking across a destabilizing rock surface.
AB  - It is important to understand how people adapt their gait when walking in real
      world conditions with variable surface characteristics. This study quantified
      lower-extremity joint kinematics, estimated whole body center of mass height
      (COM(VT)), and minimum toe clearance (MTC) while 15 healthy, young subjects
      walked on level ground (LG) and a destabilizing loose rock surface (RS) at four
      controlled speeds. There were no significant differences in average step
      parameters (length, time, or width) between the walking surfaces. However, the
      variability of these parameters increased twofold on the RS compared to LG. When
      walking on the RS, subjects contacted the surface with a flatter foot and
      increased knee and hip flexion, which enabled them to lower COM(VT). Subjects
      exhibited increased hip and knee flexion and ankle dorsiflexion during swing on
      the RS. These changes contributed to a 3.8 times greater MTC on the RS compared
      to LG. Peak hip and knee flexion during early stance and swing increased with
      walking speed, contributing to decreased COM(VT) and increased MTC. Overall,
      subjects systematically adapted their movement kinematics to overcome the
      challenge imposed by the destabilizing loose rock surface.

PMID- 21890362
TI  - The effects of symmetric and asymmetric foot placements on sit-to-stand joint
      moments.
AB  - The purpose of this study was to determine the effects of symmetric and
      asymmetric foot placements on joint moments during sit-to-stand movements. Three
      symmetric (foot-neutral, foot-back, and foot-intermediate) and three asymmetric
      foot placements (preferred stagger, nonpreferred stagger, and intermediate
      stagger) were tested. Standard (46 cm) and low (41 cm) seat heights were chosen
      to represent an average public seat height and a 10% lower seat height. Using
      inverse dynamics, maximum ankle plantarflexion, knee extension, hip extension,
      and hip abduction moments were calculated. Hip extension moments were
      significantly increased when using foot-neutral as compared to foot-back. Ankle
      plantarflexion and knee extension moments were significantly increased when a
      foot was placed in the posterior position as compared to the anterior position
      for preferred and nonpreferred stagger. Knee extension moments were significantly
      increased at the low seat height as compared to the standard seat height. When
      shifting the feet anterior or posterior for symmetric placements during sit-to
      stand, the most dramatic effect was an increase in hip extension moments when the
      feet are shifted anteriorly. Utilizing asymmetric foot placements during sit-to
      stand produced increases in ankle plantarflexion and knee extension moments for
      the posteriorly placed limb, with reductions in the anteriorly placed limb.

PMID- 21890363
TI  - Responsiveness of the single-limb stance test.

PMID- 21890364
TI  - Biochemical and anisotropical properties of tendons.
AB  - Tendons are formed by dense connective tissue composed of an abundant
      extracellular matrix (ECM) that is constituted mainly of collagen molecules,
      which are organized into fibrils, fibers, fiber bundles and fascicles
      helicoidally arranged along the largest axis of the tendon. The biomechanical
      properties of tendons are directly related to the organization of the collagen
      molecules that aggregate to become a super-twisted cord. In addition to collagen,
      the ECM of tendons is composed of non-fibrillar components, such as proteoglycans
      and non-collagenous glycoproteins. The capacity of tendons to resist mechanical
      stress is directly related to the structural organization of the ECM. Collagen is
      a biopolymer and presents optical anisotropies, such as birefringence and linear
      dichroism, that are important optical properties in the characterization of the
      supramolecular organization of the fibers. The objective of this study was to
      present a review of the composition and organization of the ECM of tendons and to
      highlight the importance of the anisotropic optical properties in the study of
      alterations in the ECM.

PMID- 21890365
TI  - Measurement of nanomechanical properties of biomolecules using atomic force
      microscopy.
AB  - The capabilities of atomic force microscopy (AFM) have been rapidly expanding
      beyond topographical imaging to now allow for the analysis of a wide range of
      properties of diverse materials. The technique of nanoindentation, traditionally
      performed via dedicated indenters can now be reliably achieved using AFM
      instrumentation, enabling mechanical property determination at the nanoscale
      using the high spatial and force resolutions of the AFM. In the study of
      biological systems, from biomolecules to complexes, this technique provides
      insight into how mesoscale properties and functions may arise from a myriad of
      single biomolecules. In vivo and in situ analyses of native structures under
      physiological conditions as well as the rapid analysis of molecular species under
      a variety of experimental treatments are made possible with this technique. As a
      result, AFM nanoindentation has emerged as a critical tool for the study of
      biological systems in their natural state, further contributing to both
      biomaterial design and pharmacological research. In this review, we detail the
      theory and progression of AFM-based nanoindentation, and present several
      applications of this technique as it has been used to probe biomolecules and
      biological nanostructures from single proteins to complex assemblies. We further
      detail the many challenges associated with mechanical models and required
      assumptions for model validity. AFM nanoindentation capabilities have provided an
      excellent improvement over conventional nanomechanical tools and by integration
      of topographical data from imaging, enabled the rapid extraction and presentation
      of mechanical data for biological samples.

PMID- 21890366
TI  - An international round-robin calibration protocol for nanoindentation
      measurements.
AB  - Nanoindentation has become a common technique for measuring the hardness and
      elastic-plastic properties of materials, including coatings and thin films. In
      recent years, different nanoindenter instruments have been commercialised and
      used for this purpose. Each instrument is equipped with its own analysis software
      for the derivation of the hardness and reduced Young's modulus from the raw data.
      These data are mostly analysed through the Oliver and Pharr method. In all cases,
      the calibration of compliance and area function is mandatory. The present work
      illustrates and describes a calibration procedure and an approach to raw data
      analysis carried out for six different nanoindentation instruments through
      several round-robin experiments. Three different indenters were used, Berkovich,
      cube corner, spherical, and three standardised reference samples were chosen,
      hard fused quartz, soft polycarbonate, and sapphire. It was clearly shown that
      the use of these common procedures consistently limited the hardness and reduced
      the Young's modulus data spread compared to the same measurements performed using
      instrument-specific procedures. The following recommendations for nanoindentation
      calibration must be followed: (a) use only sharp indenters, (b) set an upper cut
      off value for the penetration depth below which measurements must be considered
      unreliable, (c) perform nanoindentation measurements with limited thermal drift,
      (d) ensure that the load-displacement curves are as smooth as possible, (e)
      perform stiffness measurements specific to each instrument/indenter couple, (f)
      use Fq and Sa as calibration reference samples for stiffness and area function
      determination, (g) use a function, rather than a single value, for the stiffness
      and (h) adopt a unique protocol and software for raw data analysis in order to
      limit the data spread related to the instruments (i.e. the level of drift or
      noise, defects of a given probe) and to make the H and E(r) data intercomparable.

PMID- 21890367
TI  - Insights into the structure and composition of the peritubular dentin organic
      matrix and the lamina limitans.
AB  - Dentin is a mineralized dental tissue underlying the outer enamel that has a
      peculiar micro morphology. It is composed of micrometer sized tubules that are
      surrounded by a highly mineralized structure, called peritubular dentin (PTD),
      and embedded in a collagen-rich matrix, named intertubular dentin. The PTD has
      been thought to be composed of a highly mineralized collagen-free organic matrix
      with unknown composition. Here we tested the hypothesis that proteoglycans and
      glycosaminoglycans, two important organic structural features found in dentin,
      are key participants in the microstructure and composition of the PTD. To test
      this hypothesis dentin blocks were demineralized with 10 vol% citric acid for 2
      min and either digested with 1mg/ml TPCK-treated trypsin with 0.2 ammonium
      bicarbonate at pH 7.9 (TRY) or 0.1 U/mL C-ABC with 50mM Tris, 60mM sodium acetate
      and 0.02% bovine serum albumin at pH 8.0 (C-ABC). TRY is known to cleave the
      protein core of dentin proteoglycans, whereas C-ABC is expected to selectively
      remove glycosaminoglycans. All specimens were digested for 48 h in 37 degrees C,
      dehydrated in ascending grades of acetone, immersed in HMDS, platinum coated and
      imaged using an FE-SEM. Images of demineralized dentin revealed a meshwork of
      noncollagenous fibrils protruding towards the tubule lumen following removal of
      the peritubular mineral and confirmed the lack of collagen in the peritubular
      matrix. Further, images revealed that the peritubular organic network originates
      from a sheet-like membrane covering the entire visible length of tubule, called
      lamina limitans. Confirming our initial hypothesis, after the digestion with C
      ABC the organic network appeared to vanish, while the lamina limitans was
      preserved. This suggests that glycosaminoglycans are the main component of the
      PTD organic network. Following digestion with TRY, both the organic network and
      the lamina limitans disappeared, thus suggesting that the lamina limitans may be
      primarily composed of proteoglycan protein cores. In summary, our results provide
      novel evidence that (1) PTD lacks collagen fibrils, (2) PTD contains an organic
      scaffold embedded with mineral and (3) the PTD organic matrix is manly composed
      of glycosaminoglycans, whereas the lamina limitans is primarily made of
      proteoglycans protein cores.

PMID- 21890368
TI  - Measurement of 56Fe activity produced in inelastic scattering of neutrons created
      by cosmic muons in an iron shield.
AB  - We report on the study of the intensities of several gamma lines emitted after
      the inelastic scattering of neutrons in (56)Fe. Neutrons were produced via
      nuclear processes induced by cosmic muons in the 20tons massive iron cube placed
      at the Earth's surface and used as a passive shield for the HPGe detector.
      Relative intensities of detected gamma lines are compared with the results
      collected in the same iron shield by the use of the (252)Cf neutrons. Assessment
      against the published data from neutron scattering experiments at energies up to
      14MeV is also provided. It allowed us to infer the qualitative information about
      the average energy of muon-created neutrons in the iron shield.

PMID- 21890369
TI  - Proton beam simulation with MCNPX/CINDER'90: Germanium metal activation estimates
      below 30MeV relevant to the bulk production of arsenic radioisotopes.
AB  - Germanium metal targets encapsulated in Nb shells were irradiated in a proton
      beam. Proton and secondary neutron beam fluences as well as radionuclide activity
      formation were modeled using MCNPX in combination with CINDER90. Targets were
      chemically processed using distillation and anion exchange. Good agreement
      between the measured radiochemical yields and MCNPX/CINDER90 estimates was
      observed. A target of pentavalent (73,74)As radioarsenic for neutron activation
      studies was prepared.

PMID- 21890370
TI  - Au Lalpha x-rays induced by photons from 241Am: Comparison of experimental
      results and the predictions of PENELOPE.
AB  - The results of experiments performed, measuring the Lalpha x-rays emitted by Au
      due to excitation by photons of various energies from an (241)Am sample at
      forward-scattered angles in the range 0 degrees  to 65 degrees , are compared to
      the predictions of the Monte Carlo code, PENELOPE. The experimental data are in
      good agreement with the predictions of the program. A comparison of the angular
      distributions of the probability densities (as predicted by the program) related
      to the Au Lalpha and Lbeta x-rays suggests that PENELOPE does not simulate the
      phenomena described by Flugge et al. (1972).

PMID- 21890371
TI  - The radiolabeling of proteins by the [18F]AlF method.
AB  - A new ([(18)F]AlF)(2+)-binding ligand that contains 1,4,7-triazacyclononane-1,4
      diacetate (NODA) attached to a methyl phenylacetic acid group (MPA) was
      conjugated to N-(2-aminoethyl)maleimide (EM) to form NODA-MPAEM. The NODA-MPAEM
      was labeled with ([(18)F]AlF)(2+) at 105 degrees C in 49-82% yield and conjugated
      at room temperature to an antibody Fab' fragment in 69-80% yield (total time
      ~50min) and with retention of immunoreactivity. These data indicate that the
      rapid and simple [(18)F]AlF-labeling method can be easily adapted for preparing
      heat-sensitive compounds with (18)F quickly and in high yields.

PMID- 21890372
TI  - Jaw cysts - filling or no filling after enucleation? A review.
AB  - INTRODUCTION: Jaw cysts are common lesions in the oral and maxillofacial region.
      Enucleation of the lesions and primary closure of the defects, the so-called
      "cystectomy", has evolved as the treatment of choice. In order to reduce
      infections and to accelerate bone regeneration, different types of bone grafts
      are increasingly investigated for defect filling. MATERIAL AND METHODS: The
      present review reflects the most recent studies using autogenous, allogenic,
      xenogenic and alloplastic bone grafts and compares the results to current
      investigations about conservative cyst enucleation without using any filling
      materials. Relevant studies with significant patient sample sizes were
      electronically searched in PubMed and Medline. RESULTS: Simple cyst enucleation
      and blood clot healing show low complication rates and sufficient bone
      regeneration even in large defects. Prospective randomized trials comparing the
      additional use of filling materials to the "cystectomy" are rare. Currently
      available data do not indicate the superiority of additional bone grafts.
      CONCLUSION: Enucleation of jaw cysts and primary closure without bone substitutes
      remains "state of the art" in most cases.

PMID- 21890373
TI  - Histopathological evaluation of the effect of intranasal phototherapy on nasal
      mucosa in rabbits.
AB  - Allergic rhinitis is a high-incidence allergic inflammation of the nasal airways
      that impacts quality of life. Of the numerous therapies used to treat allergic
      rhinitis, intranasal phototherapy has emerged as a promising new treatment
      modality for inflammatory airway disease. Phototherapy is widely used for the
      treatment of immune-mediated skin diseases because its profound immunosuppressive
      effect inhibits hypersensitivity reactions in the skin. Intranasal phototherapy
      using a combination of Ultraviolet-A (UVA) and Ultraviolet-B (UVB) plus Visible
      light (VIS) has been shown to suppress the clinical symptoms of allergic
      rhinitis, but limited data regarding its adverse effects on the nasal mucosa
      currently exists. In this study, we demonstrate that UV displays no harmful
      effects on the nasal mucosa cells of rabbits following 2 weeks of intranasal
      phototherapy.

PMID- 21890374
TI  - Interferon regulatory factor-4 activates IL-2 and IL-4 promoters in cooperation
      with c-Rel.
AB  - Interferon regulatory factor (IRF)-4 is a member of the IRF transcription factor
      family, whose expression is primarily restricted to lymphoid and myeloid cells.
      In T-cells, IRF-4 expression is induced by T-cell receptor (TCR) cross-linking or
      treatment with phorbol-12-myristate-13-acetate (PMA)/Ionomycin, and IRF-4 is
      thought to be a critical factor for various functions of T-cells. To elucidate
      the IRF-4 functions in human adult T-cell leukemia virus type 1 (HTLV-1)-infected
      T-cells, which constitutively express IRF-4, we isolated IRF-4-binding proteins
      from T-cells, using a tandem affinity purification (TAP)-mass spectrometry
      strategy. Fourteen proteins were identified in the IRF-4-binding complex,
      including endogenous IRF-4 and the nuclear factor-kappaB (NF-kappaB) family
      member, c-Rel. The specific association of IRF-4 with c-Rel was confirmed by
      immunoprecipitation experiments, and IRF-4 was shown to enhance the c-Rel
      dependent binding and activation of the interleukin-4 (IL-4) promoter region. We
      also demonstrated that IL-2 production was also enhanced by exogenously-expressed
      IRF-4 and c-Rel in the presence of P/I, in T-cells, and that the optimal IL-2 and
      IL-4 productions in vivo was IRF-4-dependent using IRF-4-/- mice. These data
      provide molecular evidence to support the clinical observation that elevated
      expression of c-Rel and IRF-4 is associated with the prognosis in adult T-cell
      leukemia/lymphoma (ATLL) patients, and present possible targets for future gene
      therapy.

PMID- 21890375
TI  - Adiponectin stimulates release of CCL2, -3, -4 and -5 while the surface abundance
      of CCR2 and -5 is simultaneously reduced in primary human monocytes.
AB  - The adipokine adiponectin is well known to affect the function of immune cells
      and upregulation of CCL2 by adiponectin in monocytes/macrophages has already been
      reported. In the current study the effect of adiponectin on CCL2, -3, -4, and -5
      and their corresponding receptors CCR1, CCR2, and CCR5 has been analyzed.
      Adiponectin elevates mRNA and protein of the CC chemokines in primary human
      monocytes. Simultaneously the surface abundance of CCR2 and CCR5 is reduced while
      CCR1 is not affected. Downregulation of CCR2 by adiponectin is blocked by a CCR2
      antagonist although expression of the CCL2 regulated genes CCR2 and TGF-beta 1 is
      not altered in the adiponectin-incubated monocytes. CCL2, -3, and -5
      concentrations measured in supernatants of monocytes of normal-weight (NW),
      overweight (OW), and type 2 diabetic (T2D) patients positively correlate with BMI
      and are increased in obesity and T2D. In contrast CCL4 is similarly abundant in
      the supernatants of all of these monocytes. The degree of adiponectin-mediated
      induction of the chemokines CCL3, -4, and -5 negatively correlates with their
      basal levels and upregulation of CCL3 and CCL5 is significantly impaired in OW
      and T2D cells. Serum concentrations of these chemokines are almost equal in the
      three groups and do not correlate with the levels in monocyte supernatants. In
      conclusion these data demonstrate that adiponectin stimulates release of CCL2 to
      CCL5 in primary human monocytes, and induction in cells of overweight probands is
      partly impaired. Adiponectin also lowers surface abundance of CCR2 and CCR5 and
      downregulation of CCR2 seems to depend on autocrine/paracrine effects of CCL2.

PMID- 21890377
TI  - Quality, safety and efficacy of follow-on biologics in Japan.
AB  - Recently, WHO, EU, Japan and Canada have published guidelines on
      biosimilar/follow-on biologics. While there seems to be no significant difference
      in the general concept in these guidelines, the data to be submitted for product
      approval are partially different. Differences have been noted in the requirements
      for comparability studies on stability, prerequisites for reference product, or
      for the need of comparability exercise for determination of process-related
      impurities. In Japan, there have been many discussions about the amount and
      extent of data for approval of follow-on biologics. We try to clarify the
      scientific background and rational for regulatory pathway of biosimilar/follow-on
      biologics in Japan in comparison with the guidelines available from WHO, EU and
      Canada. In this article, we address and discuss the scientific background
      underlying these differences to facilitate the harmonization of follow-on
      biologic principles in the guidelines in future.

PMID- 21890376
TI  - Blockade of hypoxia-inducible factor-1alpha by YC-1 attenuates interferon-gamma
      and tumor necrosis factor-alpha-induced intestinal epithelial barrier
      dysfunction.
AB  - Proinflammatory cytokines play vital roles in intestinal barrier function
      disruption. YC-1 has been reported to have potent anti-inflammatory properties,
      and to be a potential agent for sepsis treatment. Here, we investigated the
      protective effect of YC-1 against intestinal barrier dysfunction caused by
      interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). To
      assess the protective effect of YC-1 on intestinal barrier function, Caco-2
      monolayers treated with simultaneous IFN-gamma and TNF-alpha were used to measure
      transepithelial electrical resistance (TER) and paracellular permeability. To
      determine the mechanisms involved in the protective action of YC-1, expression
      and distribution of tight junction proteins ZO-1 and occludin in Caco-2
      monolayers challenged with simultaneous IFN-gamma and TNF-alpha were analyzed by
      Western blot and immunofluorescence, respectively. Expressions of phosphorylated
      myosin light chain (MLC), MLC kinase (MLCK) and hypoxia-inducible factor-1alpha
      (HIF-1alpha) were analyzed by Western blot in IFN-gamma and TNF-alpha-treated
      Caco-2 monolayers. It was found that YC-1 attenuated barrier dysfunction caused
      by IFN-gamma and TNF-alpha, and also prevented IFN-gamma and TNF-alpha-induced
      morphological redistribution of tight junction proteins ZO-1 and occludin in Caco
      2 monolayers. In addition, YC-1 suppressed IFN-gamma and TNF-alpha-induced
      upregulation of MLC phosphorylation and MLCK protein expression. Furthermore,
      enhanced expression of HIF-1alpha in Caco-2 monolayers treated with IFN-gamma and
      TNF-alpha was also suppressed by YC-1. It is suggested that YC-1, by
      downregulating MLCK expression, attenuates intestinal barrier dysfunction induced
      by IFN-gamma and TNF-alpha, in which HIF-1alpha inhibition, at least in part,
      might by involved. YC-1 may be a potential agent for treatment of intestinal
      barrier disruption in inflammation.

PMID- 21890378
TI  - Women in HIV conference research: trends and content analysis of abstracts
      presented at 17 HIV/AIDS conferences from 2003 to 2010.
AB  - OBJECTIVE: HIV/AIDS conferences provide an opportunity to review current research
      from around the world. Conferences are a good gauge of the amount of research
      conducted on HIV/AIDS and women because papers are disseminated widely and
      publicly, and can represent published or unpublished material. The objective of
      this study was to conduct content analysis and data coding to quantify trends in
      women-specific research in HIV/AIDS abstracts at the International AIDS
      Conferences (AIDS), the Canadian Association for HIV Research (CAHR) Conferences,
      and the Conferences on Retroviruses and Opportunistic Infections (CROI) over a 7
      year time period. METHODS: Abstracts titles and text containing female keywords
      were retrieved from the AIDS, CAHR, and CROI conferences between 2003 and 2009
      and coded according to research category using content analysis. RESULTS: Over
      34,000 abstracts were searched. A total of 5,221 abstracts related to women
      (13.7%) were found over 7 years. Women-specific abstracts represented 16.2% (n =
      4,245/26,175) at AIDS, 13.7% (n = 257/1,876) at CAHR, and 11.1% (n = 719/6,370)
      at CROI. The AIDS and CAHR conferences demonstrated a slightly increasing trend
      in women-specific abstracts over 7 years. In categorical coding, the most
      prevalent research category was reproductive health, and the most infrequent was
      policy and program evaluation. CONCLUSION: The AIDS conferences showed an
      increase in women-specific abstracts over time, probably owing to a gender policy
      implemented in 2008 and a women's research award. The CAHR conference instituted
      a gender policy in 2011, and the CROI conference should follow suit. Conference
      abstracts should include breakdown and analysis by gender.

PMID- 21890379
TI  - Motor commands for fast point-to-point arm movements are customized for small
      changes in inertial load.
AB  - For repeated point-to-point arm movements it is often assumed that motor commands
      are customized in a trial-to-trial manner, based on previous endpoint error. To
      test this assumption, we perturbed movement execution without affecting the
      endpoint error by using a modest manipulation of inertia. Participants made point
      to-point elbow flexion and extension movements in the horizontal plane, under the
      instruction to move as fast as possible from one target area to another. In
      selected trials the moment of inertia of the lower arm was increased or decreased
      by 25%. First, we found that an unexpected increase or decrease of inertia did
      not affect the open loop controlled part of the movement path (and thus endpoint
      error was not affected). Second, we found that when the increased or decreased
      inertia was presented repeatedly, after 5-11 trials motor commands were
      customized: the first 100ms of agonistic muscle activity in the smoothed and
      rectified electromyographic signal of agonistic muscles was higher for the high
      inertia compared to the low inertia. We conclude that endpoint error is not the
      only parameter that is used to evaluate if motor commands lead to movements as
      planned.

PMID- 21890380
TI  - Quality improvement guidelines for the performance of inferior vena cava filter
      placement for the prevention of pulmonary embolism.

PMID- 21890381
TI  - Personal consequences of malpractice lawsuits on American surgeons.
AB  - BACKGROUND: Our objective was to identify the prevalence of recent malpractice
      litigation against American surgeons and evaluate associations with personal well
      being. Although malpractice lawsuits are often filed against American surgeons,
      the personal consequences with respect to burnout, depression, and career
      satisfaction are poorly understood. STUDY DESIGN: Members of the American College
      of Surgeons were sent an anonymous, cross-sectional survey in October 2010.
      Surgeons were asked if they had been involved in a malpractice suit during 2
      previous years. The survey also evaluated demographic variables, practice
      characteristics, career satisfaction, burnout, and quality of life. RESULTS: Of
      the approximately 25,073 surgeons sampled, 7,164 (29%) returned surveys.
      Involvement in a recent malpractice suit was reported by 1,764 of 7,164 (24.6%)
      responding surgeons. Surgeons involved in a recent malpractice suit were younger,
      worked longer hours, had more night call, and were more likely to be in private
      practice (all p <0.0001). Recent malpractice suits were strongly related to
      burnout (p < 0.0001), depression (p < 0.0001), and recent thoughts of suicide (p
      < 0.0001) among surgeons. In multivariable modeling, both depression (odds ratio
      = 1.273; p = 0.0003) and burnout (odds ratio = 1.168; p = 0.0306) were
      independently associated with a recent malpractice suit after controlling for all
      other personal and professional characteristics. Hours worked, nights on call,
      subspecialty, and practice setting were also independently associated with recent
      malpractice suits. Surgeons who had experienced a recent malpractice suit
      reported less career satisfaction and were less likely to recommend a surgical or
      medical career to their children (p < 0.0001). CONCLUSIONS: Malpractice lawsuits
      are common and have potentially profound personal consequences for US surgeons.
      Additional research is needed to identify individual, organizational, and
      societal interventions to support surgeons subjected to malpractice litigation.

PMID- 21890382
TI  - Proposed competencies in geriatric patient care for use in assessment for initial
      and continued board certification of surgical specialists.

PMID- 21890383
TI  - A phase II study of mitomycin, fluorouracil, folinic acid, and irinotecan (MFI)
      for the treatment of transitional cell carcinoma of the bladder.
AB  - BACKGROUND AND OBJECTIVES: Cisplatin-based chemotherapy is standard care for
      metastatic transitional cell carcinoma (TCC) of the urinary tract. However it is
      not appropriate for all patients, particularly those with poor renal function.
      There is no clear consensus on the optimal regimen for these individuals or for
      those after cisplatin failure. Here we present data using mitomycin, 5
      fluorouracil, and irinotecan (MFI) in these patients. MATERIALS AND METHODS:
      Patients with TCC, who had either received cisplatin-based chemotherapy
      previously or who were not deemed fit for cisplatin therapy (creatinine clearance
      was less than 60 ml/min) were eligible for treatment with the experimental
      combination chemotherapy regimen MFI. RESULTS: Thirty-six patients were treated
      with MFI between 2001 and 2004. Overall response rate was 19% and median overall
      survival (OS) was 5.4 months (95% CI 3.3-8.4 months). The response rate and
      overall survival in both groups was 19% and 5.4 months, respectively, (95% CI 2.9
      7.1 months) in the pretreated and 2.5- 9.3 months in the untreated. The most
      common toxicity was malaise (grade 3 or 4 = 28%). CONCLUSIONS: MFI appear to be a
      combination which requires further investigation in patients where cisplatin and
      gemcitabine are not applicable.

PMID- 21890384
TI  - Type two "endoleak": medical jargon that causes significant anxiety in patients.

PMID- 21890386
TI  - Carotid endarterectomy within seven days after the neurological index event is
      safe and effective in stroke prevention.
AB  - BACKGROUND: Timing of surgery remains a controversial subject with some concerns
      persisting that the benefit of early carotid endarterectomy (CEA) offsets the
      perioperative risks. We investigated the neurological outcome of patients with
      symptomatic internal carotid artery (ICA) stenosis after surgery in relation to
      the timing of treatment. METHODS: From January 2005 to June 2010, 468 patients (n
      = 349 male, 74.6%, median age 71 years) underwent CEA for symptomatic stenosis.
      Perioperative morbidity and mortality rates were assessed in the 30 days' follow
      up. RESULTS: The median time interval between index event and CEA was 7 days; the
      overall stroke and death rate reached 3.4%. There was no difference in the 30
      days' rate of stroke /death rate, depending on the timing of surgery (n = 5/241,
      2.1% in patients treated within 1 week vs. n = 10/215, 4.7% in patients treated
      thereafter, p = 0.12). Patients with a postoperative neurological deterioration
      had more often an ischaemic infarction on preoperative cerebral computed
      tomography (CCT) compared with those without deterioration (n = 6/15, 40.0% vs. n
      = 39/441, 9.0%, p = 0.003). Logistic regression analysis showed that patients
      with preoperative infarction on CCT had the highest risk for postoperative
      neurological deterioration. CONCLUSION: An infarction on the preoperative CCT
      leads to an increased risk for a postoperative deterioration after CEA. Patients
      should be treated at an early point in time with bland CCTs.

PMID- 21890387
TI  - Comments regarding 'Vascular access for haemodialysis in patients with central
      vein thrombosis'.

PMID- 21890389
TI  - Introduction to: A k-space analysis of small-tip-angle excitation.
AB  - The article "A k-space analysis of small-tip-angle excitation" introduced a
      spatial frequency interpretation of the effect of RF excitation pulses. This
      introduction describes where the initial ideas for this paper came from, and
      traces out some of the applications that have been developed using this
      perspective.

PMID- 21890390
TI  - Addendum to the paper "Dead-time free measurement of dipole-dipole interactions
      between electron spins" by M. Pannier, S. Veit, A. Godt, G. Jeschke, and H.W.
      Spiess [J. Magn. Reson. 142 (2000) 331-340].
AB  - The development of four-pulse DEER as described, which has been published in the
      Journal of Magnetic Resonance more than 10 years ago. The corresponding paper is
      an example where a slight advance, such as adding a refocusing pulse, which in
      retrospect looks so simple, can have a remarkable impact on an entire field of
      science. In our case it offered a simple way to exact measurements of distances
      between defined species in the nanometer range. The current applications are
      mainly in determining structures of proteins and nucleic acids.

PMID- 21890391
TI  - "Development of REDOR rotational-echo double-resonance NMR" by Terry Gullion and
      Jacob Schaefer [J. Magn. Reson. 81 (1989) 196-200].
AB  - The popularity of rotational-echo double-resonance (REDOR) NMR arises from its
      ability to measure weak dipolar couplings and long-range heteronuclear distances
      accurately. This ability was not anticipated in the first REDOR experiments and
      resulted from the effectiveness of a simple radiofrequency phase alternation
      scheme to suppress amplitude and phase distortions in echo trains even after
      hundreds of pi pulses.

PMID- 21890392
TI  - The spectrum of phenylketonuria genotypes in the Armenian population:
      identification of three novel mutant PAH alleles.
AB  - We present the spectrum of phenylalanine hydroxylase (PAH) gene mutations upon
      investigating 35 index patients identified with hyperphenylalaninemia in Armenia.
      One patient was diagnosed with dihydropteridine reductase (DHPR) deficiency,
      whereas all other 34 and their 6 affected siblings presented with mild or
      classical phenylketonuria (PKU). By analyzing all 13 exons plus exon-intron
      boundaries of the PAH gene, we identified two mutant alleles in 23 PKU patients,
      three mutations in 1, only one mutation in 5, and no mutation in 5 PKU patients.
      The most prevalent mutation was the well defined splicing error in intron 10,
      c.1066-11G>A (17/68 alleles). The three alterations, c.836C>T (p.Pro279Leu) in
      exon 7, c.1129T>G (p.Tyr377Asp) in exon 11, and c.1244A>T (p.Asp415Val) in exon
      12, have not been reported in the PAH locus database (http://www.pahdb.mcgill.ca)
      and, thus, might be specific for the culturally homogenous Armenian population.

PMID- 21890393
TI  - [Rectal cancer: The radiation basis of radiotherapy, target volume].
AB  - Since the implementation of preoperative chemoradiotherapy and mesorectal
      excision, the 5-year rates of locoregional failures in T3-T4 N0-N1 M0 rectal
      cancer fell from 25-30% thirty years ago to 5-8% nowadays. A critical analysis of
      the locoregional failures sites and mechanisms, as well as the identification of
      nodal extension, helps the radiation oncologist to optimize the radiotherapy
      target definition. The upper limit of the clinical target volume is usually set
      at the top of the third sacral vertebra. The lateral pelvic nodes should be
      included when the tumor is located in the distal part of the rectum. The anal
      sphincter and the levator muscles should be spared when a conservative surgery is
      planned. In case of abdominoperineal excision, the ischiorectal fossa and the
      sphincters should be included in the clinical target volume. A confrontation with
      radiologist and surgeon is mandatory to improve the definition of the target
      volumes to be treated.

PMID- 21890394
TI  - Determining the maximum diameter for holes in the shoe without compromising shoe
      integrity when using a multi-segment foot model.
AB  - Measuring individual foot joint motions requires a multi-segment foot model, even
      when the subject is wearing a shoe. Each foot segment must be tracked with at
      least three skin-mounted markers, but for these markers to be visible to an
      optical motion capture system holes or 'windows' must be cut into the structure
      of the shoe. The holes must be sufficiently large avoiding interfering with the
      markers, but small enough that they do not compromise the shoe's structural
      integrity. The objective of this study was to determine the maximum size of hole
      that could be cut into a running shoe upper without significantly compromising
      its structural integrity or changing the kinematics of the foot within the shoe.
      Three shoe designs were tested: (1) neutral cushioning, (2) motion control and
      (3) stability shoes. Holes were cut progressively larger, with four sizes tested
      in all. Foot joint motions were measured: (1) hindfoot with respect to midfoot in
      the frontal plane, (2) forefoot twist with respect to midfoot in the frontal
      plane, (3) the height-to-length ratio of the medial longitudinal arch and (4) the
      hallux angle with respect to first metatarsal in the sagittal plane. A single
      subject performed level walking at her preferred pace in each of the three shoes
      with ten repetitions for each hole size. The largest hole that did not disrupt
      shoe integrity was an oval of 1.7cm*2.5cm. The smallest shoe deformations were
      seen with the motion control shoe. The least change in foot joint motion was
      forefoot twist in both the neutral shoe and stability shoe for any size hole.
      This study demonstrates that for a hole smaller than this size, optical motion
      capture with a cluster-based multi-segment foot model is feasible for measure
      foot in shoe kinematics in vivo.

PMID- 21890395
TI  - An analysis of contact stiffness between a finger and an object when wearing an
      air-cushioned glove: the effects of the air pressure.
AB  - Air-cushioned gloves have the advantages of lighter weight, lower cost, and
      unique mechanical performance, compared to gloves made of conventional
      engineering materials. The goal of this study is to analyze the contact
      interaction between fingers and object when wearing an air-cushioned glove. The
      contact interactions between the the fingertip and air bubbles, which is
      considered as a cell of a typical air-cushioned glove, has been analyzed
      theoretically. Two-dimensional finite element models were developed for the
      analysis. The fingertip model was assumed to be composed of skin layers,
      subcutaneous tissue, bone, and nail. The air bubbles were modeled as air sealed
      in the container of nonelastic membrane. We simulated two common scenarios: a
      fingertip in contact with one single air bubble and with two air cushion bubbles
      simultaneously. Our simulation results indicated that the internal air pressure
      can modulate the fingertip-object contact characteristics. The contact stiffness
      reaches a minimum when the initial air pressure is equal to 1.3 and 1.05 times of
      the atmosphere pressure for the single air bubble and the double air bubble
      contact, respectively. Furthermore, the simulation results indicate that the
      double air bubble contact will result in smaller volumetric tissue strain than
      the single air bubble contact for the same force.

PMID- 21890396
TI  - Apomorphine infusion in advanced Parkinson's patients with subthalamic
      stimulation contraindications.
AB  - BACKGROUND: The efficacy of continuous subcutaneous apomorphine infusion (APO)
      has been evaluated in advanced Parkinson's disease in several open-label studies
      but never in a population of patients for whom subthalamic nucleus deep brain
      stimulation (STN-DBS) was contraindicated. METHODS: The aim of this study was to
      evaluate the efficacy and cognitive safety of APO at 12-month follow-up in 23
      advanced parkinsonian patients (mean age: 62.3 years; mean disease duration: 13.9
      years) whose dopa-resistant axial motor symptoms and/or cognitive decline
      constituted contraindications for STN-DBS. Their motor and cognitive status were
      evaluated before APO and 12 months afterwards. RESULTS: After one year, patients
      expressed high levels of satisfaction, with a mean rating on the Visual Analog
      Scale of 52.8% under APO. Daily OFF time, recorded in a 24-h diary, was reduced
      by 36% and ON time improved by 48%. There was a significant reduction (-26%) in
      mean oral levodopa equivalent dose. Dopa-resistant axial symptoms and
      neuropsychological performance remained stable. No adverse event was noted and
      none of the patients needed to take clozapine at any time. CONCLUSIONS: APO is
      both safe and effective in advanced parkinsonian patients with untreatable motor
      fluctuations, for whom STN-DBS is contraindicated due to dopa-resistant axial
      motor symptoms and/or cognitive decline. As such, it should be regarded as a
      viable alternative for these patients.

PMID- 21890397
TI  - Does the region of pain influence the presence of sensorimotor disturbances in
      neck pain disorders?
AB  - Impairments in sensorimotor control have been demonstrated in neck pain
      disorders. However, there are more anatomical and neurophysiological connections
      between the sensorimotor control system and the upper cervical region and thus
      potential for greater disturbances in those with upper region pain. This study
      investigated whether sensorimotor impairment was greater in those suffering pain
      from the upper rather than lower cervical spine region, taking the onset of pain
      into account. Sixty-four subjects with persistent neck pain were divided into 4
      groups -upper and lower region non-traumatic and upper and lower region
      traumatic. Cervical Joint Position Error (JPE), smooth pursuit neck torsion
      (SPNT) and standing balance tests were compared between groups. The lower non
      traumatic group demonstrated significantly less (p < 0.03) deficit in SPNT
      compared to all other groups as well as less total energy of sway on the eyes
      open balance tests (p < 0.05) compared to both traumatic neck pain groups. The
      upper traumatic group demonstrated significantly greater JPE following rotation
      to the right (p < 0.04) when compared to both lower groups. Less sensorimotor
      dysfunction appears to occur in those with lower compared to upper cervical
      region pain, although this depends on whether trauma is involved in the onset of
      pain.

PMID- 21890398
TI  - Clinical presentation and management of mTOR inhibitor-associated stomatitis.
AB  - Anti-cancer agents that inhibit the mTOR pathway are associated with a number of
      unique toxicities, with one of the most significant and potentially dose-limiting
      being stomatitis. The objective of this study was to report the clinical features
      and management outcomes of a series of cancer patients who developed painful mTOR
      inhibitor-associated stomatitis (mIAS). Seventeen cancer patients developed mIAS
      while being treated with everolimus- or ridaforolimus-containing protocols at the
      Dana-Farber Cancer Institute and were referred to the oral medicine clinic for
      evaluation and management. Clinical characteristics, toxicity management, and
      outcomes were summarized. In addition, the frequency and rationale for dose
      reductions and therapy discontinuation were assessed. The median duration of mTOR
      inhibitor therapy was 80 days (range 9-187 days). The median time to development
      of mouth ulcers was 10 days (range 4-25 days). Five patients required protocol
      directed dose reductions due to grades 2 and 3 stomatitis and one patient
      discontinued cancer treatment due to mouth ulcers. Clinical improvement and pain
      relief was reported in 86.6% of patients following topical, intralesional, or
      systemic corticosteroid therapy, with side effects limited to secondary
      candidiasis (n=2). Mouth ulcers are a common and potentially dose limiting
      toxicity associated with the use of mTOR inhibitors in cancer treatment. This
      case series demonstrates that local and systemic corticosteroid therapy is an
      effective approach to managing patients with symptomatic mIAS. Prospective
      studies are necessary to evaluate the effectiveness of treatment and prevention
      strategies with the ultimate goal of improving overall cancer treatment outcomes.

PMID- 21890399
TI  - Fluorescence "Turn-On" chemosensor for the selective detection of beryllium.
AB  - A new fluorogenic method for selective and sensitive determination of beryllium
      using 2,6-diphenyl-4-benzo-9-crown-3-pyrane (DBCP) was developed. The proposed
      fluorescent probe undergoes fluorescent emission intensity enhancement upon
      binding to beryllium ions in MeOH/H(2)O (70:30, v/v) solution. The fluorescence
      enhancement of DBCP is attributed to a 1:1 complex formation between DBCP and
      Be(2+) ion, which has been utilized as the basis for selective detection of
      Be(2+) ion. With the optimum condition described, the fluorescence enhancement at
      531 nm was linear to the concentration of beryllium in the range of 1.6*10(-8)
      1.6*10(-7) M and a detection limit of 1.5*10(-9) M. The fluorescent probe
      exhibits high selectivity for Be(2+) ion over the other common mono, di- and
      trivalent cations.

PMID- 21890400
TI  - A novel fluorescent sensor for Cr3+ based on rhodamine-cored poly (amidoamine)
      dendrimer.
AB  - A novel poly (amidoamine) (PAMAM) dendrimer, comprising rhodamine B unit in the
      core and 1-phenyl-3-methyl-5-pyrazolone unit at the periphery, has been
      synthesized and characterized. The dendrimer shows dramatic increase in its
      fluorescence intensity in the presence of proton and metal cations, especially in
      the presence of Cr(3+). The complex formed by dendrimer and Cr(3+) in ethanol
      solution has also been studied, considering the potential application for Cr(3+)
      fluorescent sensor. The influence of the unique chemical structure and resulted
      photoinduced electron transfer, as well as spirolactam ring-opening on the
      photophysical properties of the product has been investigated.

PMID- 21890401
TI  - Interaction of sodium benzoate with trypsin by spectroscopic techniques.
AB  - The toxicity of sodium benzoate to trypsin was investigated by fluorescence
      spectroscopy, synchronous fluorescence spectroscopy, UV-visible absorption
      spectroscopy and circular dichroism (CD) spectroscopy under mimic physiological
      conditions. Sodium benzoate could unfold trypsin by decreasing the beta-sheet
      structure, which leads to more exposure of internal amino acid groups and the
      obvious intrinsic fluorescence quenching with the rising concentration of sodium
      benzoate. The results of spectroscopic measurements indicated that sodium
      benzoate changed the internal microenvironment of trypsin and induced the
      alteration of the whole molecule, which were performed toxic effects on the
      organism. Trypsin and sodium benzoate interacted with each other to produce a
      substance by van der Waals forces and hydrogen bond, the model of which was shown
      by AutoDock software.

PMID- 21890402
TI  - Effect of Bi2O3 on spectroscopic and structural properties of Er3+ doped cadmium
      bismuth borate glasses.
AB  - Glasses with composition 20CdO.xBi(2)O(3).(79.5-x)B(2)O(3) (15<=x<=35, x in mol%)
      containing 0.5 mol% of Er(3+) ions were prepared by melt-quench technique (1150
      degrees C in air). The amorphous nature of the glasses was confirmed by X-ray
      diffraction. The spectroscopic properties of the glasses were investigated using
      optical absorption spectra and fluorescence spectra. The phenomenological Judd
      Ofelt intensity parameters Omega(lambda) (lambda=2, 4, 6) were determined from
      the spectral intensities of absorption bands in order to calculate the radiative
      transition probability (A(R)), radiative life time (tau(R)), branching ratios
      (beta(R)) for various excited luminescent states. Using the near infrared
      emission spectra, full width at half maxima (FWHM), stimulated emission cross
      section (sigma(e)) and figure of merit (FOM) were evaluated and compared with
      other hosts. Especially, the numerical values of these parameters indicate that
      the emission transition (4)I(13/2)->(4)I(15/2) at 1.506 MUm in Er(3+)-doped
      cadmium bismuth borate glasses may be useful in optical communication.

PMID- 21890403
TI  - Bridging two translation gaps: a new informatics research agenda for
      telemonitoring of chronic disease.
AB  - OBJECTIVE: To propose a research agenda that addresses technological and other
      knowledge gaps in developing telemonitoring solutions for patients with chronic
      diseases, with particular focus on detecting deterioration early enough to
      intervene effectively. DESIGN: A mixed methods approach incorporating literature
      review, key informant, and focus group interviews to gain an in-depth,
      multidisciplinary understanding of current approaches, and a roadmapping process
      to synthesise a research agenda. RESULTS: Counter to intuition, the research
      agenda for early detection of deterioration in patients with chronic diseases is
      not only primarily about advances in sensor technology but also much more about
      the problems of clinical specification, translation, and interfacing. The
      ultimate aim of telemonitoring is not fully agreed between the actors (patients,
      clinicians, technologists, and service providers). This leads to unresolved
      issues such as: (1) How are sensors used by patients as part of daily routines?
      (2) What are the indicators of early deterioration and how might they be used to
      trigger alerts? (3) How should alerts lead to appropriate levels of responses
      across different agencies and sectors? CONCLUSION: Attempts to use telemonitoring
      to improve the care of patients with chronic diseases over the last two decades
      have so far failed to lead to systems that are embedded in routine clinical
      practice. Attempts at implementation have paid insufficient attention to
      understanding patient and clinical needs and the complex dynamics and
      accountabilities that arise at the level of service models. A suggested way ahead
      is to co-design technology and services collaboratively with all stakeholders.

PMID- 21890405
TI  - Serendipity in nerve excitability research.

PMID- 21890404
TI  - Amplitude- and velocity-dependency of rigidity measured at the wrist in
      Parkinson's disease.
AB  - OBJECTIVE: Quantify the effects of increased amplitude and rate of muscle stretch
      on parkinsonian rigidity. METHODS: Eighteen subjects with Parkinson's disease
      participated in this study. Subjects' tested hand was passively displaced through
      60 degrees  and 90 degrees  ranges of wrist flexion and extension at velocities
      of 50 degrees /s and 280 degrees /s in both treated and untreated conditions.
      Joint angular position, resistance torque, and surface electromyography (EMG) of
      the wrist flexors and extensors were recorded. Rigidity was quantified by
      normalized work scores and normalized angular impulses for flexion and extension,
      separately. Reflex responses of stretched and shortened muscles were quantified
      by mean EMG and EMG ratio. A series of ANOVAs was performed to determine the
      effect of amplitude, velocity and medication on selected variables. RESULTS: Both
      work scores and angular impulses revealed that the larger displacement amplitude
      and the higher velocity were associated with significantly greater rigidity,
      increased EMG ratio and mean EMG of stretched muscles. Dopaminergic medication
      was not associated with a reduction in rigidity. CONCLUSIONS: Parkinsonian
      rigidity is modulated by the amplitude and rate of muscle stretch. SIGNIFICANCE:
      These findings shed light on the biomechanical underpinnings and physiological
      characteristics of rigidity and may inform clinical rigidity assessment in
      Parkinson's disease.

PMID- 21890406
TI  - Synthesis of (-)-beta-caryophyllene oxide via regio- and stereoselective
      endocyclic epoxidation of beta-caryophyllene with Nemania aenea SF 10099-1 in a
      liquid-liquid interface bioreactor (L-L IBR).
AB  - Nemania aenea SF 10099-1, a basidiomycete isolated from a forest soil sample,
      regio- and stereoselectively epoxidized beta-caryophyllene (Car) to (-)-beta
      caryophyllene oxide (Car-Ox) in a liquid-liquid interface bioreactor (L-L IBR)
      consisted of a liquid medium (a bottom phase), a fungus-ballooned microsphere
      (MS) mat (a middle phase), and an organic phase containing Car (a top phase). The
      cultivation conditions, such as carbon and nitrogen sources, kind of MS, initial
      medium pH and Car concentration, were optimized in the L-L IBR system. The best
      carbon and nitrogen sources were xylose and tryptone, respectively. The most
      suitable polyacrylonitrile MS was MMF-DE-1 (former MFL-80SDE; non-coated type).
      Although the strain could not grow below pH 5.5, the endocyclic epoxidation of
      Car efficiently proceeded at a wide range of initial medium pH (6.0 to 9.0). The
      bioconversion system exhibited an excellent alleviation effect toward substrate
      and product inhibitions. While Car could be added into an organic phase (KF-96L
      1CS, dimethyl silicone oil) at 50% (w/v), the accumulation of Car-Ox reached over
      30g/l in spite of these strong microbial toxicities. Moreover, the epoxidation
      reaction smoothly proceeded in a novel L-L IBR system, a multistory L-L IBR
      systems, consisted of 5 stacked reactor units. The optical rotation of Car-Ox
      produced was (-) and the enantiomeric excesses of (-)-beta-Car-Ox purified by 1st
      and 2nd recrystallization from methanol reached 97.51 and 99.33%, respectively.

PMID- 21890407
TI  - Effects of BmKIT3R gene transfer on the development and survival of silkworm
      Bombyx mori.
AB  - To verify the effects of gain-of-function mutation of the BmKIT3(R) gene (from
      the Chinese scorpion Buthus martensii Karsch) on the development and survival
      rate of insects and to explore a novel strategy for pest control, the effects of
      BmKIT3(R) gene transfer on the development and survival rate of silkworms were
      investigated. A novel transgenic vector derived from the piggyBac transposon with
      the BmKIT3(R) gene controlled by the Bmhsp20.4 promoter was transferred into
      silkworm eggs. Transgenic silkworms were obtained after screening with GFP and
      G418 antibiotics and verification by PCR and dot hybridization. The results
      showed that the oviposition number decreased by 18.9%, and the hatching and final
      survival rates were approximately 63% and 47.5%, respectively. Some 18.9% of
      surviving pupae died before developing into moths in the G3 generation. A
      specific band corresponding to BmKIT3(R) was detected for transgenic silkworms by
      Western blotting. This indicates that the Bmhsp 20.4 promoter has constitutive
      expression activity. The significant decrease in the survival rate suggests that
      pest population numbers could be effectively controlled by using BmKIT3(R) gene
      transfer. Furthermore, it can be speculated that pupal development to moths could
      be blocked if BmKIT3(R) were specially expressed in the pupal stage and reeling
      with fresh cocoons was performed.

PMID- 21890408
TI  - Right atrial mass after open heart surgery: tumour or thrombus?
AB  - Detection of a rapidly growing mass in the right atrium during routine inter
      echocardiogram follow-up period in two patients after corrective open-heart
      surgery raises concerns about nature of the mass and the probable cause. One
      turned out to be an atrial myxoma that grew rapidly over a eight month period and
      the other a well encapsulate thrombus in a fully anticoagulated patient.
      Preoperative transthoracic echocardiogram had reported both the cases to be a
      myxoma. This article highlights the importance of considering rare causes in the
      face of a seemingly obvious diagnosis and possible use of imaging modalities in
      the management of these cases.

PMID- 21890409
TI  - 'Necrosome'-induced inflammation: must cells die for it?
AB  - Necrosis, a form of death characterized by rupture of the cell membrane, is
      closely interlinked with inflammation. Cellular components released during
      necrotic death can trigger inflammation. Conversely, inflammation often yields
      tissue damage and, as a consequence, cell death. Which occurs first--necrosis or
      inflammation--in specific in vivo situations is currently difficult to tell. A
      way out of this 'chicken-and-egg' conundrum may be found via the recent finding
      that both necrotic cell death and inflammation can be initiated by a distinct set
      of signaling proteins, the 'necrosome', that includes receptor-interacting
      protein (RIP)1, RIP3 and caspase-8. Further clarifying the function of these
      signaling proteins should make it possible to establish when they induce
      inflammation directly and when inflammation is caused by necrotic cell death.

PMID- 21890410
TI  - mTOR: A pathogenic signaling pathway in developmental brain malformations.
AB  - The mTOR signaling network functions as a pivotal regulatory cascade during the
      development of the cerebral cortex. Aberrant hyperactivation of mTOR as a
      consequence of loss-of-function gene mutations encoding mTOR inhibitor proteins
      such as TSC1, TSC2, PTEN and STRADalpha has been recently linked to developmental
      cortical malformations associated with epilepsy and neurobehavioral disabilities.
      Investigation of mTOR signaling in these disorders provides for the first time
      exciting future avenues for assessment of biomarkers, patient stratification and
      prognostic measures as well as the opportunity for targeted therapy to regulate
      mTOR activity across all age groups. As we learn more about mTOR and its activity
      in the developing brain, many challenges will arise that must be overcome before
      widespread clinical therapeutics can be implemented.

PMID- 21890411
TI  - Metchnikoff's policemen: macrophages in development, homeostasis and
      regeneration.
AB  - Over the past decade, modern genetic tools have permitted scientists to study the
      function of myeloid lineage cells, including macrophages, as never before.
      Macrophages were first detected more than a century ago as cells that ingested
      bacteria and other microbes, but it is now known that their functional roles are
      far more numerous. In this review, we focus on the prevailing functions of
      macrophages beyond their role in innate immunity. We highlight examples of
      macrophages acting as regulators of development, tissue homoeostasis, remodeling
      (the reorganization or renovation of existing tissues) and repair. We also detail
      how modern genetic tools have facilitated new insights into these mysterious
      cells.

PMID- 21890413
TI  - Identification and validation of candidate biomarkers involved in human ovarian
      autoimmunity.
AB  - Antibodies to multiple ovarian antigens have been proposed as markers of ovarian
      autoimmunity. The role of ovarian autoantibodies has been widely discussed in the
      pathophysiology of premature ovarian failure and unexplained infertility, but the
      autoantigens are yet to be identified. Three immunodominant ovarian autoantigens,
      alpha-actinin 4 (alphaACTN4), heat shock 70 protein 5 (HSPA5) and beta-actin
      (ACTB), have been identified using anti-ovarian antibody-positive sera from women
      with idiopathic premature ovarian failure (n=50) and women undergoing IVF
      (n=695), using mass spectrometry. These autoantigens were subsequently validated
      using Western blot, immunohistochemistry and enzyme-linked immunosorbent assay.
      These autoantigens are localized to different components of the ovary such as the
      ooplasm of the oocyte, theca, granulosa, corpus luteum and zona pellucida. All
      the above antigens were found to be expressed in the ooplasm throughout
      follicular development. All the autoantigens are expressed specifically in the
      oocyte except alphaACTN4. The three autoantigens could contribute to the array of
      biomarkers to be used for developing specific and sensitive tests for diagnosis
      of women at risk of premature ovarian failure and IVF failure due to ovarian
      autoimmunity and could give an insight into the molecular mechanisms involved in
      the pathophysiology of these conditions.

PMID- 21890412
TI  - Balancing acts: the role of TGF-beta in the mucosal immune system.
AB  - The gastrointestinal mucosal immune system faces unique challenges in dealing not
      only with fed antigens but also both commensal and pathogenic bacteria. It is
      tasked with digesting, transporting and using nutritional antigens while
      protecting the host from pathogenic organisms. As such, mechanisms that mediate
      effective immunity and immune tolerance are active within the gut environment. To
      accomplish this, the mucosal immune system has evolved sophisticated mechanisms
      that safeguard the integrity of the mucosal barrier. Transforming growth factor
      beta (TGF-beta) emerges as a key mediator, balancing the tolerogenic and
      immunogenic forces at play in the gut. In this review, we discuss the role of TGF
      beta in the generation and functioning of gut lymphocyte populations. We
      highlight recent findings, summarize controversies, outline remaining questions
      and provide our personal perspectives.

PMID- 21890414
TI  - PPE_MPTR genes are differentially expressed by Mycobacterium tuberculosis in
      vivo.
AB  - The PPE_MPTR protein sub-family is unique to mycobacteria and comprises proteins
      found only in MTB complex and in few other pathogenic mycobacteria. Very little
      is known about the precise function of PPE_MPTR, as well as on the expression
      pattern and the transcriptional regulation of their structural genes. In the
      present work, real time RT-PCR techniques were used to determine the expression
      profile of PPE_MPTR genes of Mycobacterium tuberculosis during infection in vivo
      and in different culture conditions. The PPE_MPTR genes showed a similar
      expression profile in axenic cultures, with a significant increase of gene
      expression following exposure to environmental signals such as SDS, isoniazid and
      ethambutol. The PPE_MPTR genes were expressed in lung and spleen tissues infected
      by M. tuberculosis, and levels of expression were similar to those of genes
      encoding M. tuberculosis virulence factors such as hbhA and mpt64. Levels and
      pattern of gene expression in host tissues were different for each PPE_MPTR gene
      under study. The results of this study indicate that PPE_MPTR genes are
      differentially regulated in the lung and spleen tissues during M. tuberculosis
      infection, suggesting that each gene responds independently to the different and
      complex environmental signals encountered in host tissues.

PMID- 21890416
TI  - Commentary to 'persistent renin-angiotensin system activation after anti-reflux
      surgery and its management'.

PMID- 21890415
TI  - Long-term extracorporeal photochemotherapy in a pediatric patient with refractory
      sclerodermatous chronic graft-versus-host disease.
AB  - Sclerodermatous chronic graft-versus-host disease (cGVHD) following allogeneic
      hematopoietic stem cell transplantation (HSCT) in children is difficult to treat
      and life-threatening. Extracorporeal photochemotherapy (ECP; photopheresis), an
      immunomodulatory therapy that involves the infusion of autologous peripheral
      blood leukocytes after ex vivo exposure to the photoactive agent 8
      methoxypsoralen and ultraviolet A radiation, is an effective treatment for
      steroid-refractory cGVHD. After undergoing allogeneic HSCT for pre-B-cell acute
      lymphoblastic leukemia, a 14-year-old boy developed extensive sclerodermatous
      cGVHD that was refractory to prednisone, tacrolimus, and sirolimus. ECP was
      administered over the course of 53 months, during which the skin softened
      substantially and immunosuppressive therapy was discontinued. This case suggests
      that long-term ECP is a viable option in children with sclerodermatous cGVHD.

PMID- 21890417
TI  - Impact of insurance status on access to care and out-of-pocket costs for U.S.
      individuals with epilepsy.
AB  - We analyzed data from the 2002-2007 Medical Expenditure Panel Survey (MEPS) to
      assess whether individuals with epilepsy who are uninsured and those who have
      Medicaid coverage experience differences in medical resource utilization or out
      of-pocket costs compared with those having other types of insurance. With
      sociodemographic characteristics controlled for, uninsured individuals had
      significantly fewer outpatient visits, fewer visits with neurologists, and
      greater antiepileptic drug costs than did those with private insurance.
      Individuals with Medicaid coverage had similar medical resource utilization rates
      but lower out-of-pocket costs compared with privately insured individuals. These
      findings indicate substantial barriers to receipt of appropriate medical care for
      uninsured individuals with epilepsy, but not for those with Medicaid coverage.
      Future studies should evaluate whether ongoing changes to the US health care
      system are able to address the differences in care we found among uninsured
      individuals with epilepsy and should incorporate measures of disease severity and
      unmet need.

PMID- 21890418
TI  - Ictal fear auras after selective amygdalohippocampectomy: the use of ictal SPECT
      and scalp EEG in the presurgical reevaluation.
AB  - The perception of fear aura in complex partial seizures is linked to epileptic
      discharges within mesial temporal lobe structures. Although selective
      amygdalohippocampectomy often leads to favorable seizure control, persistence of
      fear auras after surgery can hamper quality of life significantly. We describe
      two patients with persistent fear auras after selective amygdalohippocampectomy
      who had to be reevaluated for a second operative procedure. In one patient, ictal
      SPECT revealed focal hyperperfusion within the left temporal pole. In the other
      patient, localization of the focus was possible with ictal scalp EEG, which
      revealed closely time-related focal theta activity in the right frontotemporal
      electrodes. Both patients underwent a second surgery leading to complete
      remission. The persistence of fear auras after selective amygdalohippocampectomy
      provides an example of involvement of a complex neuronal network in the
      generation of this emotional state during mesiotemporal lobe seizures. Ictal
      SPECT or ictal scalp EEG may be valuable in identifying the involved areas and in
      guiding the surgeon to render these patients seizure free.

PMID- 21890419
TI  - Heredity in epilepsy: neurodevelopment, comorbidity, and the neurological trait.
AB  - The genetic bases of common, nonmendelian epilepsy have been difficult to
      elucidate. In this article, we argue for a new approach to genetic inquiry in
      epilepsy. In the latter part of the 19th century, epilepsy was universally
      acknowledged to be part of a wider "neurological trait" that included other
      neuropsychiatric conditions. In recent years, studies of comorbidity have shown
      clear links between epilepsy and various neuropsychiatric disorders including
      psychosis and depression, and genetic studies of copy number variants (CNVs) have
      shown that in some cases, the same CNV underpins neuropsychiatric illness and
      epilepsy. Functional annotation analysis of the sets of genes impacted by
      epilepsy CNVs shows enrichment for genes involved with neural development, with
      gene ontological (GO) categories including "neurological system process"
      (P=0.006), "synaptic transmission" (P=0.009), and "learning or memory" (P=0.01).
      These data support the view that epilepsy and some neuropsychiatric conditions
      share pathogenic neurodevelopmental pathways, and that epilepsy should be
      included in the spectrum of neurodevelopmental disorders. Yet, most current
      genetic research in epilepsy has restricted samples to specific types of epilepsy
      categorized according to the clinical classification schemes on the basis of
      seizure type, anatomical location, or epilepsy syndrome. These schemes are, to an
      extent, arbitrary and do not necessarily align with biological reality. We
      propose an alternative approach that makes no phenotypic assumptions beyond
      including epilepsy in the neurodevelopmental spectrum. A "'value-free" strategy
      of reverse phenotyping may be worth exploring, starting with genetic association
      and looking backward at the phenotype. Finally, it should be noted that there are
      societal implications to associating epilepsy with other neuropsychiatric
      disorders, and it is vital to ensure research in this area does not result in
      increased stigma for patients with epilepsy.

PMID- 21890420
TI  - Predisposition to epilepsy in fragile X syndrome: does the Val66Met polymorphism
      in the BDNF gene play a role?
AB  - Epilepsy is detected in about 23% of patients with fragile X syndrome (FXS).
      Absence or reduced levels of the fragile X mental retardation protein (FMRP), a
      global regulator of translation in neurons and an important factor in synaptic
      plasticity, produce the observed epileptic patterns. The brain-derived
      neurotrophic factor (BDNF) gene is a specific regulator of synaptic plasticity,
      and disturbances in its function cause dendrite abnormalities similar to those
      observed in FXS. A putative reciprocal regulation of FMRP and BDNF has been
      hypothesized. The Val66Met polymorphism in the BDNF gene may be involved in the
      alteration of normal secretion of the mature peptide and may modulate the
      epileptic phenotype observed in some patients with FXS. We investigated the
      relationship of this Met66 allele to the prevalence of epilepsy in 77 patients
      with FXS. No association was observed between this polymorphism and epilepsy in
      our group of patients. Therefore, it should not be considered a biomarker for
      developing epilepsy in patients with FXS.

PMID- 21890421
TI  - Adjunctive lacosamide in clinical practice: sodium blockade with a difference?
AB  - Lacosamide (LCM) was licensed in the United Kingdom in 2008 for the adjunctive
      treatment of partial-onset seizures. It exerts its effect by enhancing sodium
      channel slow inactivation. This article reports preliminary outcomes with
      adjunctive LCM in the everyday clinical setting. To date, 113 patients (57 males,
      56 females; aged range=18-74 years, median=39 years) with uncontrolled partial
      onset seizures (monthly frequency range=1-300, median=4) have been included in
      the audit. Patients were taking 1-4 (median=1) antiepileptic drugs (AEDs), having
      previously tried 1-12 (median 3) drug schedules. After 12 weeks on stable AED
      dosing, LCM was added, aiming at an initial target range of 200-400mg/day. Review
      took place every 6-8 weeks until one of four endpoints was reached: seizure
      freedom for >=6 months on a given LCM dose; >=50% (responder) or <50% (marginal
      benefit) seizure reduction over 6 months compared with baseline on the highest
      tolerated LCM dose; withdrawal of LCM because of lack of efficacy, side effects,
      or both. An endpoint has been reached by 65 (57.5%) patients so far. Seventeen
      (26.2%) have remained seizure free on a median daily LCM dose of 100mg (range=50
      300 mg). Patients were more likely to become seizure free when LCM was used as a
      first add-on (15/36, 41.7%), compared with a later treatment schedule (1/27,
      3.7%, P=0.001). With appropriate dose manipulation, patients taking traditional
      sodium blockers (5/26, 19.2%) were as likely to become seizure free as those
      taking AEDs with other mechanisms of action only (11/37, 29.7%). Fifty percent or
      greater seizure reduction was achieved in an additional 16 (24.6%) patients (1
      monotherapy); 18 (27.7%) reported marginal benefit. Two patients were established
      on LCM monotherapy (one seizure free, one responder). Patients remaining on LCM
      were as likely to also be taking sodium blockers only (23/27, 85.1%) as AEDs with
      other mechanisms (26/36, 72.2%). LCM was withdrawn in 14 patients (12.3% of
      ongoing patients, 21.5% of those at an endpoint; 10 for side effects, 4 for lack
      of efficacy). The most common side effects leading to withdrawal were sedation,
      ataxia, and dizziness. Of the 10 with side effects, only 2 patients took
      concomitant sodium blockers. Patients on sodium valproate were more likely to
      discontinue LCM (8/21, P=0.018) than those also taking other AEDs; 5 of the 8 did
      so because of side effects and 3 because of lack of efficacy. In patients with
      partial-onset seizures, LCM is an effective and well-tolerated adjunctive AED
      when combined with appropriate doses of traditional sodium blockers, as well as
      agents with other mechanisms of action. Seizure freedom was more likely when LCM
      was used as a first add-on compared with a later treatment schedule. Patients
      also taking sodium valproate were significantly more likely to discontinue LCM
      compared with those taking other AEDs. These data suggest that the
      pharmacological effect of LCM differs importantly from that of AEDs that
      influence fast inactivation of the sodium channel.

PMID- 21890422
TI  - Retrospective analysis of third-line and fourth-line chemotherapy for advanced
      non-small-cell lung cancer.
AB  - BACKGROUND: The efficacy of third-line and further-line chemotherapy for advanced
      non-small-cell lung cancer (NSCLC) remains unknown. PATIENTS AND METHODS: We
      evaluated the clinical outcome of third- and fourth-line chemotherapy for the
      treatment of advanced NSCLC in consecutive patients who received first-line
      chemotherapy at our institute between July 2002 and June 2006. From a hospital
      based registry, the following data were extracted: (a) patient characteristics,
      (b) type of chemotherapeutic agents, and (c) objective response and survival
      data. RESULTS: A total of 599 patients were included in this analysis. Overall,
      69.3%, 38.4%, 17.7%, and 6.0% of the patients received second-, third-, fourth-,
      and fifth-line chemotherapy, respectively. Significant differences in age (P <
      .0001), performance status at the start of first-line chemotherapy (P < .0001),
      and histology (P = .0175) were observed between patients who received third-line
      chemotherapy and those who did not. Docetaxel, gefitinib, and S-1 were the most
      frequently used regimens for third- or fourth-line chemotherapy. Five percent of
      the patients had participated in phase I trials of investigational new drugs. The
      objective response rates and disease control rates of third- and fourth-line
      chemotherapy were 17.0% and 34.4% and 11.3% and 24.5%, respectively. The median
      survival times (95% confidence interval [CI]) from the start of first-, second-,
      third-, and fourth-line chemotherapy until death were 15.3 months (95% CI, 13.8
      16.5 months), 12.8 months (95% CI, 10.7-14.5 months), 12.0 months (95% CI, 9.3
      14.2 months), and 9.9 months (95% CI, 8.6-12.0 months), respectively. CONCLUSION:
      As many as 38% of patients with advanced NSCLC who received first-line
      chemotherapy could receive third-line chemotherapy. This result emphasizes the
      need for randomized controlled trials of third-line treatment in patients with
      advanced NSCLC.

PMID- 21890423
TI  - "Spring-back" closure associated with open-door cervical laminoplasty.
AB  - BACKGROUND CONTEXT: Spring-back complication after open-door laminoplasty as
      described by Hirabayashi is a well-known risk, but its definition, incidence, and
      associated neurologic outcome remain unclear. OBJECTIVE: To investigate the
      incidence and the neurologic consequence of spring-back closure after open-door
      laminoplasty. STUDY DESIGN: A retrospective radiographic and clinical review.
      OUTCOME MEASURES: Lateral cervical spine X-rays were evaluated. Anteroposterior
      diameters (APD) of the vertebral canal of C3-C7 were measured. Spring-back was
      defined as loss of APD on follow-up in comparison to immediate postoperative
      canal expansion. The loss of the end-on lamina silhouette with consequent
      reappearance of the lateral profile of the spinous processes was also assessed to
      verify the presence of spring-back. Spring-back closure was classified based on
      whether the collapse was total or partial, and whether all the operated levels or
      only a subset had collapsed (ie, complete vs. partial closure, segmental closure
      vs. total-construct closure). Neurologic status was documented using the Japanese
      Orthopaedic Association (JOA) score. METHODS: Thirty consecutive patients who
      underwent open-door laminoplasty from 1995 to 2005 at a single institution with a
      minimum follow-up of 2 years were assessed. They were all operated on using the
      classic Hirabayashi technique. Radiographic outcomes were assessed independently
      by two individuals. RESULTS: Sixteen men and 14 women with an average follow-up
      of 5 years (range, 2-12 years) were included. Of these patients, 24 had cervical
      spondylotic myelopathy and six had ossification of the posterior longitudinal
      ligament. Spring-back closure was found in three patients (10%) and 7 of 117
      laminae (6%) within 6 months of the operation, which was further confirmed by
      computed tomography and magnetic resonance imaging. All spring-back closures were
      partial segmental closures. Gender and age were not significant factors related
      to spring back (p>.05). The mean JOA score on follow-up was 12.5, with a recovery
      rate of 40%. All patients with spring back and available JOA data exhibited
      postoperative neurologic deterioration. Of the three patients with spring back,
      two patients underwent revision surgery, whereas one declined. CONCLUSIONS:
      Spring-back closure occurred in 10% of our patients at or before 6 months after
      surgery. The incidence of spring-back by level (ie, 117 laminae) was 6%, mainly
      occurring at the lower cervical spine. All spring-back closures were partial
      segmental closures, most commonly involving C5 and C6. Postoperative neurologic
      deficit was associated with spring-back closure; therefore, surgeons should adopt
      preemptive surgical measures to prevent the occurrence of such a complication.

PMID- 21890424
TI  - Medication reconciliation: identifying medication discrepancies in acutely ill
      hospitalized older adults.
AB  - BACKGROUND: Medication discrepancies may occur during transitions from community
      to acute care hospitals. The elderly are at risk for such discrepancies due to
      multiple comorbidities and complex medication regimens. Medication reconciliation
      involves verifying medication use and identifying and rectifying discrepancies.
      OBJECTIVE: The aim of this study was to describe the prevalences and types of
      medication discrepancies in acutely ill older patients. METHODS: Patients who
      were >= 70 years and were admitted to any of 3 acute care for elders (ACE) units
      over a period of 2 nonconsecutive months in 2008 were prospectively enrolled.
      Medication discrepancies were classified as intentional, undocumented
      intentional, and unintentional. Unintentional medication discrepancies were
      classified by a blinded rater for potential to harm. This study was primarily
      qualitative, and descriptive (univariate) statistics are presented. RESULTS:
      Sixty-seven patients (42 women; mean [SD] age, 84.0 [6.5] years) were enrolled.
      There were 37 unintentional prescription-medication discrepancies in 27 patients
      (40.3%) and 43 unintentional over-the-counter (OTC) medication discrepancies in
      19 patients (28.4%), which translates to Medication Reconciliation Success Index
      (MRSI) of 89% for prescription medications and 59% for OTC medications. The
      overall MRSI was 83%. More than half of the prescription-medication discrepancies
      (56.8%) were classified as potentially causing moderate/severe discomfort or
      clinical deterioration. CONCLUSION: Despite a fairly high overall MRSI in these
      patients admitted to ACE units, a substantial proportion of the prescription
      medication discrepancies were associated with potential harm.

PMID- 21890425
TI  - Roux-en-Y gastric bypass improves hepatic mitochondrial function in obese rats.
AB  - BACKGROUND: Obesity-related fatty liver disease is linked to mitochondrial
      dysfunction and oxidative stress. Nuclear factor (erythroid-derived 2)-like 2
      (Nrf2) regulates mitochondrial function and is a transcriptor of multiple genes
      that produce antioxidants. Because Roux-en-Y gastric bypass (RYGB) improves fatty
      liver and decreases the oxidative stress in the liver, we hypothesized that RYGB
      activates Nrf2 and increases cytochrome C oxidase subunit II (COX-II) in the
      liver of obese rats. METHODS: Sprague-Dawley rats were fed a high-fat diet for 16
      weeks. The obese rats underwent either RYGB (n = 20) or a sham operation (n =
      20). The tissues were harvested 13 weeks postoperatively. The nuclear fraction
      and mitochondrial extracts were used for protein analysis with immunoblotting.
      Immunostaining was done on liver sections for COX-II, Nrf2, and the macrophage
      marker ED2 and F4/80. The gels were quantified using densitometry; P <= .05 was
      considered significant. RESULTS: RYGB increased COX-II expression in the liver
      sections (3330 +/- 56 versus 2056 +/- 37 for RYGB versus sham, P < .001). The
      total (nuclear and cytoplasmic) Nrf2 expression was high in the obese sham
      operated control (2456 +/- 45 versus 4352 +/- 76, RYGB versus sham, P < .001).
      However, the nuclear fraction of Nrf2 was significantly increased in the RYGB
      liver (2341 +/- 46 versus 1352 +/- 35, RYGB versus sham, P < .001). Furthermore,
      Nrf2 protein co-localized with the molecular markers of Kupffer cells.
      CONCLUSIONS: Diet-induced fatty liver is associated with mitochondrial
      dysfunction. RYGB increases COX-II, which is involved in mitochondrial
      respiration, and increases the nuclear translocation of the Nrf2 transcriptional
      factor, which is involved in mitochondrial biogenesis and function. Taken
      together, these data suggest that surgically induced weight loss is associated
      with improved mitochondrial function in obese rats.

PMID- 21890426
TI  - Comment on: Long-term follow-up in patients undergoing open gastric bypass as a
      revisional operation for previous failed restrictive procedures.

PMID- 21890427
TI  - Carbon dioxide elimination pattern in morbidly obese patients undergoing
      laparoscopic surgery.
AB  - BACKGROUND: Hypercapnia can result from carbon dioxide pneumoperitoneum and
      adversely affect the postoperative period, particularly in morbidly obese
      patients. The purpose of the present study was to examine carbon dioxide
      homeostasis using a metabolic monitor in morbidly obese and normal weight
      patients during laparoscopic surgical procedures. The setting was a university
      hospital in Italy. METHODS: The data from 25 patients with a body mass index of
      47.7 +/- 5.5 kg/m2 undergoing laparoscopic gastric mini-bypass were compared with
      the data from 25 normal weight patients undergoing laparoscopic cholecystectomy.
      The minute ventilation was adjusted to maintain a normal arterial partial
      pressure of carbon dioxide and normal end-tidal partial pressure of carbon
      dioxide throughout surgical procedures. The arterial partial pressure of carbon
      dioxide, end-tidal partial pressure of carbon dioxide, total exhaled carbon
      dioxide per minute, and arterial blood gas analysis were obtained at 10-minute
      intervals, along with other cardiorespiratory parameters. RESULTS: The total
      exhaled carbon dioxide per minute increased by the same percentage in both groups
      (around 20%). In the laparoscopic cholecystectomy patients, a definite plateau in
      the total exhaled carbon dioxide per minute was observed within 20 minutes from
      the start of pneumoperitoneum but not in the morbidly obese patients. After
      desufflation, the total exhaled carbon dioxide per minute returned more rapidly
      to the baseline values in the laparoscopic cholecystectomy group than in the
      morbidly obese group (17.4 +/- 6.2 and 24.1 +/- 8.3 min, respectively).
      CONCLUSION: The results of our study have shown that the load of carbon dioxide
      insufflated is well tolerated in morbidly obese patients, as well as in normal
      patients, with proper intraoperative ventilation adjustments. However, after
      pneumoperitoneum, the return to a normal total exhaled carbon dioxide per minute
      required a longer period in the morbidly obese group. Prolonged mechanical
      ventilation is therefore advisable in morbidly obese patients.

PMID- 21890428
TI  - Laparoscopic conversion of laparoscopic sleeve gastrectomy to gastric bypass for
      intractable gastroesophageal reflux disease.

PMID- 21890429
TI  - Single incision laparoscopic adjustable gastric banding: 111 cases.
AB  - BACKGROUND: As single incision surgery increases in popularity, the feasibility
      of offering this approach in bariatric surgery is further progression of this
      surgical technique. With the technical challenges that both operating on the
      morbidly obese patient and single incision surgery present, we describe our
      initial experience undertaking 111 single-incision gastric band insertions.
      METHODS: From June 2009 to October 2010, 111 obese patients underwent single
      incision laparoscopic adjustable gastric banding through a single transverse
      incision using a multichannel single port and a pars flaccida technique.
      Prospective data collection was undertaken, including visual analog scores.
      RESULTS: In this initial series, the median operative time was 65 minutes (range
      34-165). There was 1 conversion to a 5-port laparoscopic technique (.9%), and an
      additional port was placed in 7 patients (6%). Male patients were more likely to
      require an additional port (P < .05). The single-incision size ranged from 26 to
      45 mm (median 35). At 23 hours postoperatively, the median pain score was 2.5 on
      a 0-10 visual analog score. On multivariate analysis, pain was found to increase
      with operation time (P < .001). The median length of stay was 24 hours (range 5.5
      48). There was no mortality and minimal morbidity, with 1 wound infection
      necessitating band removal. CONCLUSIONS: Single-incision laparoscopic adjustable
      gastric banding can be performed safely with minimal morbidity and mortality in
      the morbidly obese patient, and our technique has a high rate of success. The
      benefits compared with the traditional laparoscopic approach and long-term
      outcomes are yet to be established. However, if the intra-abdominal operative
      time is >60 minutes, one should consider the placement of an additional port,
      especially in male patients.

PMID- 21890430
TI  - Long-term follow-up after laparoscopic sleeve gastrectomy: 8-9-year results.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) has rapidly gained popularity
      as a definitive bariatric procedure despite the sparse long-term follow-up data.
      On the basis of extensive experience with the open Magenstrasse and Mill
      operation, we began practice of LSG in 2000. The objective of the present study
      was to analyze 8-9 years of our follow-up data for LSG at a university hospital
      in the United Kingdom. METHODS: From January 2000 to December 2001, 20 patients
      underwent LSG. A 32F bougie was used for calibration in all cases. RESULTS: The
      preoperative median body mass index was 45.8 kg/m(2) (range 35.8-63.7), and 9
      patients (45%) were superobese (body mass index >= 50 kg/m(2)). For LSG as a
      definitive bariatric procedure, 8-9-year follow-up data were available for 13
      patients. Of the remainder, 4 patients underwent revision surgery and 3 were lost
      to follow-up after 2 years. For the entire cohort, the median excess weight loss
      (EWL) was 73% (range 13-105%) at 1 year, 78% (range 22-98%) at 2 years, 73%
      (range 28-90%) at 3 years, and 68% (range 18-85%) at 8 or 9 years (P = .074). Of
      the 13 LSG-only patients with 8-9 years of follow-up, 11 (55% of the starting
      cohort) had >50% EWL at 8 or 9 years. No significant difference was found in the
      initial body mass index between the LSG-only patients with >50% EWL and others
      (45.9 kg/m(2), range 35.8-59.4 versus 45.7 kg/m(2), range 38.9-63.7,
      respectively; P = .70). The LSG-only patients with >50% EWL had a marginally
      significantly greater EWL at 1 year compared with the others (76%, range 48-103%
      versus 45%, range 13-99%, respectively; P = .058). CONCLUSION: At 8-9 years of
      follow-up, 55% of patients had >50% EWL from LSG as a definitive bariatric
      procedure.

PMID- 21890431
TI  - Comparative study of laparoscopic sleeve gastrectomy with and without partial
      enterectomy and omentectomy.
AB  - BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) is a novel bariatric surgical
      procedure that constitutes the first-stage procedure of laparoscopic Roux-en-Y
      gastric bypass in high-risk patients, the long-term results of which are unknown.
      Our objective was to establish whether partial enterectomy and omentectomy are
      necessary in addition to LSG to achieve weight loss in obese patients. The
      setting was a case series in a provincial hospital. METHODS: A total of 40 obese
      patients (29 women and 11 men) were separated into 2 equal groups according to
      patient choice. Group 1 underwent LSG alone, and group 2 underwent LSG plus
      partial enterectomy and omentectomy. The partial enterectomy left the first 100
      cm of the jejunum and the last 200 cm of the ileum. The data were collected
      during the follow-up examinations, performed at 1, 3, 6, and 12 months
      postoperatively. RESULTS: The body mass index loss (BMIL) was 3.9 +/- .5 kg/m(2)
      and 9.4 +/- 1.3 kg/m(2) at 1 and 12 months in group 1, respectively. The BMIL was
      4.5 +/- .9 kg/m(2) and 10.4 +/- 1.9 kg/m(2) at 1 and 12 months in group 2,
      respectively. At 1 and 12 months postoperatively, the percentage of excess body
      weight loss was 32.2% +/- 12.6% and 81.5% +/- 20.4% in group 1 and 35.5% +/-
      10.5% and 83.8% +/- 24.5% in group 2, respectively. Except for the BMIL at 1
      month after surgery, no significant differences were found in the BMIL or
      percentage of excess body weight loss. CONCLUSION: LSG with and without partial
      enterectomy and omentectomy in our study was an effective method of bariatric
      surgery, but they did not differ in their effect on weight loss. However, the
      long-term effect of weight loss with LSG alone or combined with partial
      enterectomy and omentectomy needs additional study.

PMID- 21890432
TI  - Lysophosphatidic acid induced red blood cell aggregation in vitro.
AB  - Under physiological conditions healthy RBCs do not adhere to each other. There
      are indications that RBCs display an intercellular adhesion under certain
      (pathophysiological) conditions. Therefore we investigated signaling steps
      starting with transmembrane calcium transport by means of calcium imaging. We
      found a lysophosphatidic acid (LPA) concentration dependent calcium influx with
      an EC(50) of 5 MUM LPA. Downstream signaling was investigated by flow cytometry
      as well as by video-imaging comparing LPA induced with "pure" calcium mediated
      phosphatidylserine exposure and concluded the coexistence of two branches of the
      signaling pathway. Finally we performed force measurements with holographic
      optical tweezers (HOT): The intercellular adhesion of RBCs (aggregation) exceeds
      a force of 25 pN. These results support (i) earlier data of a RBC associated
      component in thrombotic events under certain pathophysiological conditions and
      (ii) the concept to use RBCs in studies of cellular adhesion behavior, especially
      in combination with HOT. The latter paves the way to use RBCs as model cells to
      investigate molecular regulation of cellular adhesion processes.

PMID- 21890433
TI  - Exercise improves lung function and habitual activity in children with cystic
      fibrosis.
AB  - BACKGROUND: Cystic fibrosis (CF) lung disease leads to progressive deterioration
      in exercise capacity. Because physical activity has been shown to improve lung
      function and quality of life (QoL), developing routine exercise programs can
      benefit this patient population. METHODS: Lung function, nutritional status, and
      exercise capacity and assessments of habitual activity and QoL were measured
      before and after a two-month, subject-designed exercise regimen based on self
      reported activity assessment. Statistical analysis included Wilcoxon signed-rank,
      Wilcoxon rank sum, and Fisher's exact tests. RESULTS: Subjects completing the
      study demonstrated significant improvement in exercise capacity and body image
      perception, a CF-specific QoL measure (p<0.001). In secondary analyses, subjects
      improving exercise capacity showed significant increases in lung function and
      self-reported habitual activity. CONCLUSIONS: Increases in exercise capacity over
      a two-month period resulted in significantly improved lung function and self
      reported habitual activity. Longer, controlled trials are needed to develop
      individualized exercise recommendations.

PMID- 21890434
TI  - Metabolic profiling of urine in young obese men using ultra performance liquid
      chromatography and Q-TOF mass spectrometry (UPLC/Q-TOF MS).
AB  - Obesity is currently epidemic in many countries worldwide. In the young adult,
      obesity often accompanies hyperlipemia, which is strongly related to the
      occurrence and development of obesity-related chronic diseases such as diabetes
      mellitus, hypertension and cardiovascular disease. This study investigated the
      differences in metabolomic profiling between obese (with hyperlipemia, n=30) and
      normal-weight (n=30) young men. Anthropometric parameters and conventional
      metabolites were measured. There were no significant differences between obese
      and normal-weight young men in age, height and fasting plasma glucose level.
      Obese young men showed increased weight, body mass index, fat mass, systolic
      blood pressure, and triglyeride, total cholesterol and insulin levels, and lower
      levels of testosterone. The endogenous metabolite profile of urine was
      investigated by UPLC/Q-TOF MS (ultra performance liquid chromatography and Q-TOF
      mass spectrometry) with electrospray ionization (ESI). Partial least squares
      (PLS) enabled clusters to be visualized. Eight urine principal metabolites
      contributing to the clusters were identified; these included increased L-prolyl-L
      proline, leucyl-phenylalanine, and decanoylcarnitine in positive ESI mode (m/z
      213.1267, 279.1715 and 316.2459, respectively) and N-acetylornithine, 17
      hydroxypregnenolone sulfate, 11beta-hydroxyprogesterone, 5a-dihydrotestosterone
      sulfate and glucosylgalactosyl hydroxylysine in negative ESI mode (m/z 173.0931,
      411.1883, 331.185, 369.1751 and 485.1875, respectively). These metabolite changes
      in obese men suggested early changes of metabolism in young-male obesity with
      hyperlipemia. The study may further aid the clinical prevention and treatment of
      obesity and related chronic disease.

PMID- 21890435
TI  - Liquid chromatography-mass spectrometry method for the quantification of
      tamoxifen and its metabolite 4-hydroxytamoxifen in rat plasma: application to
      interaction study with biochanin A (an isoflavone).
AB  - Tamoxifen is the agent of choice for the treatment of estrogen receptor-positive
      breast cancer. Tamoxifen is a substrate of P-glycoprotein (P-gp) and microsomal
      cytochrome P450 (CYP) 3A, and biochanin A (BCA) is an inhibitor of P-gp and
      CYP3A. Hence, it could be expected that BCA would affect the pharmacokinetics of
      tamoxifen. In the present study we have developed and validated a simple,
      sensitive and specific LC-ESI-MS/MS method for the simultaneous quantification of
      tamoxifen and its metabolite 4-hydroxytamoxifen with 100 MUL rat plasma using
      centchroman as an internal standard (IS). Tamoxifen, 4-hydroxytamoxifen and IS
      were separated on a Supelco Discovery C18 (4.6 mm * 50 mm, 5.0 MUm) column under
      isocratic condition using 0.0 1M ammonium acetate (pH 4.5):acetonitrile (10:90,
      v/v) as a mobile phase. The mobile phase was delivered at a flow rate of 0.8
      mL/min. The method was proved to be accurate and precise at linearity range of
      0.78-200 ng/mL with a correlation coefficient (r) of >= 0.996. The intra- and
      inter-day assay precision ranged from 1.89 to 8.54% and 3.97 to 10.26%,
      respectively; and intra- and inter-day assay accuracy was between 87.63 and
      109.06% and 96 and 103.89%, respectively for both the analytes. The method was
      successfully applied to study the effect of oral co-administration of BCA (an
      isoflavone) on the pharmacokinetics of tamoxifen and 4-hydroxytamoxifen in female
      rats. The coadministration of BCA caused no significant changes in the
      pharmacokinetics of tamoxifen and 4-hydroxytamoxifen. However, the peak plasma
      concentration (C(max)) of 4-hydroxytamoxifen in BCA pretreated rats was
      significantly (P<0.05) lower than those from control group.

PMID- 21890436
TI  - Comparative studies of HPLC-fluorometry and LC/MS method for the determination of
      N-acetylneuraminic acid as a marker of deteriorated ophthalmic solutions.
AB  - Methods for determining the deterioration of ophthalmic solutions using both high
      performance liquid chromatography (HPLC) with fluorescence detection and liquid
      chromatography coupled with selected ion monitoring mass spectrometry (LC/MS) are
      described. The methods are based on the determination of N-acetylneuraminic acid
      (NeuAc) released by the hydrolysis of foreign bodies that contaminate eye drops
      during use. The released NeuAc was either labeled with 1,2-diamino-4,5
      methylenedioxybenzene (DMB) for fluorometric detection or detected without
      derivatization by mass spectrometry. The calibration curves for NeuAc showed good
      linearity between 1.2 ng/mL and 39 ng/mL for fluorometric HPLC and 5.0 ng/mL and
      100 ng/mL for LC/MS, respectively. Detection limits for fluorometric HPLC and
      LC/MS were 0.20 ng/mL and 0.88 ng/mL, respectively. The NeuAc content of some
      model glycoproteins determined by LC/MS method were 62-78% of those determined by
      fluorometry. The differences are attributed to matrix effects but the LC/MS
      method afforded sufficiently high sensitivity that NeuAc in the foreign bodies
      could be determined in eight of nine test samples.

PMID- 21890437
TI  - Dairy products and physical stature: a systematic review and meta-analysis of
      controlled trials.
AB  - The positive relationship between per capita availability of dairy products and
      average height found in historical studies (for instance in nineteenth century
      Bavaria, Prussia and France; Baten, 2009) does not necessarily indicate a causal
      relationship. Historical studies usually apply non-experimental methods that may
      produce substantial bias. Modern experimental controlled studies may provide high
      quality evidence supporting a causal relationship between consumption of dairy
      products and physical growth. This paper provides a systematic review and meta
      analysis of controlled trials investigating the effect of supplementing usual
      diet with dairy products on physical growth. Twelve studies provided sufficient,
      independent data for meta-analysis. Seven studies were conducted since the 1990s.
      The other studies were conducted between 1926 and 1980. Studies were conducted in
      Europe, USA, China, Northern Vietnam, Kenya, Indonesia and India. Many studies
      had some internal validity problems such as lack of randomisation or
      dissimilarity of groups at baseline regarding height and age, which affects the
      quality of evidence. Meta-analysis and sensitivity analysis showed that the most
      likely effect of dairy products supplementation is 0.4 cm per annum additional
      growth per ca 245 ml of milk daily. Meta-regression analysis indicated that milk
      might have more effect on growth than other dairy products while lower height-for
      age and being a teenager increased the effect of supplementation. In conclusion,
      there is moderate quality evidence that dairy products supplementation stimulate
      linear growth supporting hypotheses that changing levels of consumption of dairy
      products in the 19th and 20th centuries contributed to trends in height.

PMID- 21890438
TI  - Serum lipids in primary sclerosing cholangitis.
AB  - BACKGROUND: Limited data are available regarding the serum lipids in primary
      sclerosing cholangitis. AIMS: To determine the lipid levels in patients with
      primary sclerosing cholangitis. METHODS: We monitored the serum lipid levels
      annually for up to 6 years in 157 patients included in three previous trials of
      ursodeoxycholic acid. RESULTS: The baseline lipid values were: total
      cholesterol=207 mg/dL (127-433); high-density lipoprotein=56 mg/dL (26-132); low
      density lipoprotein=129 mg/dL (48-334); triglycerides=102 mg/dL (41-698).
      Cirrhotic stage was associated with lower levels of total cholesterol (186 mg/dL
      vs. 217 mg/dL, p=.02). A significant correlation between the liver biochemistries
      and total and low-density lipoprotein cholesterol levels was observed.
      Ursodeoxycholic acid, as compared to placebo, significantly decreased total (-27
      mg/dL vs. 22 mg/dL, p=.0004) and low-density lipoprotein cholesterol (-24 mg/dL
      vs. 17 mg/dL, p=.0001). After extended follow-up, small changes in the lipid
      levels were noticed. The incidence of coronary artery disease was 4%.
      CONCLUSIONS: Our findings suggest that the lipid levels in primary sclerosing
      cholangitis are often above levels where treatment with lipid-lowering agents is
      recommended. However, primary sclerosing cholangitis patients seem to have no
      elevated risk for cardiovascular events. The correlation of total and low-density
      lipoprotein cholesterol with liver biochemistries implies that mechanisms linked
      to cholestasis may regulate cholesterol metabolism.

PMID- 21890439
TI  - Adding banding ligation is effective as rescue therapy to prevent variceal
      rebleeding in haemodynamic non-responders to pharmacological therapy.
AB  - BACKGROUND: It is unknown which is the best therapy to treat haemodynamic non
      responders to pharmacological therapy after variceal bleeding. AIM: To evaluate
      the efficacy of adding banding ligation to drugs to prevent variceal rebleeding
      in haemodynamic non-responders to drugs. METHODS: Fifty-three cirrhotic patients
      with variceal bleeding underwent a hepatic venous pressure gradient (HVPG)
      measurement 5 days after the episode. Nadolol and nitrates were then titrated to
      maximum tolerated doses. A second HVPG was taken 14 days later. Responders (HVPG
      <=12 mm Hg or >=20% decrease from baseline) were maintained on drugs and non
      responders had banding ligation added to drugs. RESULTS: Mean follow-up was 28
      months. In 5 patients the second HVPG could not be performed because of early
      rebleeding. The remaining 48 patients were classified as responders (n=24) and
      non-responders (n=24), who had banding added. No baseline differences were
      observed between groups. Variceal rebleeding occurred in 12% of the 48 patients
      whose haemodynamic response was assessed. Responders on drug therapy presented a
      16% rebleeding rate, whilst non-responders rescued with banding showed an 8%
      rebleeding rate. Rebleeding-related mortality was not different between groups.
      CONCLUSION: In a HVPG-guided strategy, adding banding ligation to drugs is an
      effective rescue strategy to prevent rebleeding in haemodynamic non-responders to
      drug therapy.

PMID- 21890440
TI  - Gene expression profiling of a fish parasite Ichthyophthirius multifiliis:
      Insights into development and senescence-associated avirulence.
AB  - The ciliate parasite Ichthyophthirius multifiliis (Ich) infects many freshwater
      fish, causing white spot disease that leads to heavy economic losses to
      aquaculture and ornamental industries. Despite its economic importance, molecular
      studies examining fundamental processes such as life stage regulation and
      infectivity have been scarce. In this study, we developed an oligo microarray
      platform using all available I. multifiliis expressed sequence tag (EST)
      information as well as probes designed through comparative genomics to other
      protozoa. Gene expression profiling for developmental and virulence factors was
      conducted using this platform. For the developmental study, the microarray was
      used to examine gene expression profiles between the three major life stages of
      Ich: infective theront, parasitic trophont, and reproductive tomont. A total of
      135 putative I. multifiliis genes were found to be differentially expressed among
      all three life-stages. Examples of differentially expressed transcripts among
      life stages include immobilization antigens and epiplasmin, as well as various
      other transcripts involved in developmental regulation and host-parasite
      interactions. I. multifiliis has been shown to lose infectivity at later cell
      divisions potentially due to cellular senescence. Therefore, the microarray was
      also used to explore expression of senescence-associated genes as related to the
      passage number of the parasite. In this regard, comparison between tomont early
      and late passages yielded 493 differently expressed genes; 1478 differentially
      expressed genes were identified between trophont early and late passages. The EST
      derived oligo microarray represents a first generation array of this ciliate and
      provided reproducible expression data as validated by quantitative RT-PCR.

PMID- 21890441
TI  - An internal distraction device for Le Fort distraction osteogenesis: the NAVID
      system.
AB  - Le Fort distraction osteogenesis is sometimes applied to improve the facial
      appearance in craniofacial dysostosis or cleft lip and palate. Distraction
      devices are generally classified into external and internal types. The movement
      of external distractors can be controlled easily but their large size and the
      need for a facial mask cause much psychological stress to the patient. Internal
      distractors are smaller and better tolerated, but they are not easily
      controllable and removal is difficult. We designed an internal distraction device
      to eliminate the problems of the currently available distractors -Nakajima's
      angle-variable internal distraction (NAVID) system - and aimed to assess its
      clinical applicability. Between 2000 and 2010, we treated 16 patients with the
      NAVID system: Le Fort I, III, III + I and IV distractions were performed in
      three, five, four and four patients, respectively. Distraction was started after
      a 1-week latency period. Then, the exposed rod was cut, and the distractors were
      left in place for 3 months or more as retention devices, and thereafter removed.
      All patients showed satisfactory occlusion and facial aesthetics. Open bite
      during the consolidation period was the main complication. In conclusion, the
      NAVID system is safe, effective and reliable for all types of Le Fort distraction
      osteogenesis.

PMID- 21890442
TI  - Analysis of anatomic positioning in computer-assisted and conventional anterior
      cruciate ligament reconstruction.
AB  - INTRODUCTION: Anterior cruciate ligament (ACL) reconstruction should be anatomic
      while achieving favorable anisometric behavior to avoid impingement with the
      femoral notch. Computerization enables these biomechanical conditions to be
      optimally fulfilled; but what of anatomic positioning? The present study compared
      the positioning of tibial and femoral tunnels, drilled using either a
      conventional ACL guide or a navigation system, using the anatomic foot-print
      areas of the native ACL. MATERIAL AND METHODS: This cadaver study used
      computerized recording to compare tibial and femoral ACL attachment areas to the
      positioning of tunnels created either conventionally or under computer-guided
      navigation. RESULTS: Computer guidance enabled the tibial and femoral tunnels to
      be systematically positioned within the anatomic area and, as regards the tibial
      area, within the anterior third near to the medial tibial spine, without femoral
      notch impingement. Anisometry was in all cases favorable, at a mean 3.3 +/- 0.7
      mm; using a conventional guide, anisometry was favorable in only 50% of cases, at
      a mean 5.4 +/- 1.2 mm. CONCLUSION: Computer-guided navigation ensured implant
      positioning within the so-called anatomometric area of the native ACL attachment,
      avoiding impingement with the femoral notch. LEVEL OF EVIDENCE: Level 2.

PMID- 21890443
TI  - Metabolic syndrome and incidence of liver and breast cancers in Japan.
AB  - AIM OF THE STUDY: To clarify the relationship between the presence of metabolic
      syndrome and the incidence of cancer in a general Japanese population. METHODS: A
      retrospective cohort study was conducted among 8329 male and 15,386 female
      subjects between 1992 and 2000. The analysis used five definitions of metabolic
      syndrome. The information on the site-specific cancer was obtained from the
      population-based cancer registry. A Cox proportional hazard model was adapted for
      the statistical analyses. The average follow-up period was 9.1 years. RESULTS:
      The National Cholesterol Education Program Adult Treatment Panel III 2001
      criteria of metabolic syndrome revealed that the hazard ratio of metabolic
      syndrome for liver cancer was 1.89 (95% confidence interval (CI) 1.11-3.22) for
      males, and 3.67 (CI 1.78-7.57) for females. The hazard ratio for female breast
      cancer was 2.87 (CI 1.67-4.94). When the analysis was limited to postmenopausal
      women (55 years of age or older), the ratio increased to 6.73 (CI 2.93-15.43).
      The NCEP-ATPIII 2001 criteria were superior to the other four proposed criteria
      for predicting the incidence of cancer. In the statistical model, which included
      all components of the metabolic syndrome and the metabolic syndrome (present or
      absent), high blood glucose was a significant associated factor for all sites and
      liver cancers, whereas the metabolic syndrome was found to be a significant
      associated factor for breast cancer. CONCLUSION: Metabolic syndrome may play an
      important role in the incidence of breast cancer. High fasting plasma glucose
      level is considered to be useful as an associated factor for the incidence of all
      sites and liver cancer.

PMID- 21890444
TI  - Expressions of p53, c-MYC, BCL-2 and apoptotic index in human osteosarcoma and
      their correlations with prognosis of patients.
AB  - BACKGROUND: Nowadays it remains a controversial issue whether a correlation
      exists between the apoptosis rate of tumor tissue and the prognosis of the
      patients. The aim of the study is to investigate the relationships of apoptotic
      genes and apoptotic index of osteosarcoma tissue to prognosis of the patients,
      meanwhile to explore the valid prognostic biomarkers of osteosarcoma that will
      enhance efficacy of clinical treatments for osteosarcoma. METHODS: In our
      studies, the immunohistochemical ABC and terminal DNA breakpoints in situ 3
      hydroxy end labeling (TUNEL) techniques were used to detect the expressions of
      p53, c-MYC, BCL-2 and apoptotic index in 56 osteosarcoma specimens. The
      relationships between apoptotic genes expression and apoptotic index in
      osteosarcoma tissue and their correlations with pathologic classification and
      prognosis of osteosarcoma cases were analyzed. RESULTS: We found that the
      expressions of p53, c-MYC, and BCL-2 were negatively correlated with apoptotic
      index of osteosarcoma tissue, were not correlated with pathological types of
      osteosarcoma, and were closely related to prognosis of the patients. Moreover,
      apoptotic index of osteosarcoma tissue was positively correlated with the long
      term survival of the patients. CONCLUSION: We concluded that the expressions of
      p53, c-MYC, BCL-2 protein and apoptotic index could be used as potential biomarks
      for predicting the progression and prognosis of osteosarcoma, and for optimizing
      clinical treatments.

PMID- 21890445
TI  - Socio-economic inequalities in testicular cancer survival within two clinical
      studies.
AB  - BACKGROUND: Testicular cancer is the most common cancer in men under 35 years of
      age, and has the highest survival for adult male malignancies. Despite the fact
      that survival is very high, there is evidence that survival differs between socio
      economic groups. METHODS: We analysed survival patterns for 1606 testicular
      cancer patients diagnosed during 1984-2001 and recruited to one of two clinical
      studies. The first was a surveillance study to determine relapse-free survival
      after orchidectomy in 865 patients with stage I nonseminomatous germ-cell
      testicular cancer diagnosed during 1984-1991 (TE04). The second study was a trial
      in which 1174 men with stage I seminomatous germ-cell tumours were randomised to
      receive radiotherapy or one injection of carboplatin between 1996 and 2001
      (TE19). The number of men available for analysis from these two studies was 578
      and 1028, respectively. We followed these patients up for their vital status, and
      assigned them an ecological measure of deprivation. Crude and relative survival
      were estimated at 5 and 10 years by socio-economic deprivation. RESULTS: No
      significant socio-economic gradient was seen: 1.3% (95% CI -0.3% to 3.1%) at 5
      years and 2.1% (95% CI -0.5% to 4.7%) at 10 years. CONCLUSION: We conclude that,
      given equal treatment at a given stage of disease, survival from testicular
      cancer does not depend on socio-economic status. This suggests that the socio
      economic gradient in testicular cancer survival in the general population is more
      likely to be attributable to health care system factors than to personal or socio
      economic factors in the men themselves.

PMID- 21890446
TI  - Is salt intake an independent risk factor of stroke mortality? Demographic
      analysis by regions in Japan.
AB  - We reported a remarkable regional difference within Japan in the incidence of end
      stage renal disease. Regional differences were also well-known for salt intake,
      blood pressure (BP), and mortality from stroke, which remains one of the leading
      causes of death. Noting these regional differences, we examined mutual
      relationships among salt intake, BP, and stroke mortality in 12 regions of Japan.
      Data of salt intake, BP, and stroke mortality in 12 regions were collected from
      National Nutrition Survey (NNS-J), reanalysis of NNS-J, and Vital Statistics of
      National Population Dynamic Survey (Ministry of Health, Labor and Welfare),
      respectively. Significant regional differences were found in salt intake (P <
      .0001), mean arterial BP (P = .0001), and stroke mortality (P < .0001). Although
      annual changes in these parameters were also significant, their regional
      differences persisted. Salt intake had positive relationships with both mean
      arterial BP (r = 0.26, P = .0009) and stroke mortality (r = 0.26, P < .0001)
      across 12 regions, whereas mean arterial BP was not correlated with stroke
      mortality. Multiple regression analysis further identified salt intake as an
      independent factor to increase stroke mortality, but mean arterial BP was not a
      determinant. Compared with the four regions with lowest salt intake, odds ratios
      of stroke mortality adjusted by mean arterial BP were 1.04 (95% CI, 1.03-1.06)
      for the intermediate four regions and 1.25 (95% CI, 1.23-1.27) for the four
      regions with highest salt intake. These findings suggest that salt intake may
      have an adverse effect on stroke mortality independently of BP.

PMID- 21890447
TI  - Intravenous hydralazine for blood pressure management in the hospitalized
      patient: its use is often unjustified.
AB  - Due to observations of increased off-label use of intravenous hydralazine in area
      hospitals, we studied its use in a university teaching hospital. Patients were
      prospectively identified between April and October 2010 with a pharmacy order for
      intravenous hydralazine. Demographic and clinical information, including
      pretreatment blood pressure (BP), change in BP and heart rate within 2 hours
      after administration of hydralazine, and adverse events were obtained. Ninety
      four patients (mean age, 69 +/- 18 years, 48% women, 89% with known hypertension)
      received 201 intravenous hydralazine doses (mean dose of 11.4 +/- 4.3 mg). Only 4
      (2%) patients had evidence of an urgent hypertensive condition. Following
      hydralazine, BP was reduced by 24/9 +/- 29/15 mmHg and heart rate increased by 4
      +/- 13 beats per minute. Changes from baseline in BP were related to baseline BP.
      Seventeen patients experienced an adverse event, the most common being
      hypotension (n = 11). Intravenous hydralazine is commonly prescribed for non
      urgent cases of hypertension in the hospitalized patient. While changes in
      systolic BP are related to baseline BP values, they are highly variable, and
      associated with hypotension. Thus, this agent may not be useful for treating
      hypertension in many hospitalized patients and may cause harm if used
      inappropriately.

PMID- 21890449
TI  - Noncanonical intracrine action.
AB  - Over the past 3 decades it has become clear that a large number of extracellular
      signaling proteins/peptides also act in the intracellular space. These factors
      are termed intracrines and, although diverse in structure, they share a variety
      of functional features. In recent years, attention has increasingly turned to
      identifying the intracellular mechanisms of intracrine action and their
      implications for human disorders, such as cancer and cardiovascular disease.
      Perhaps not surprisingly, some intracrines have been shown to bind to and
      activate their cognate receptors located on intracellular membranes, such as the
      nuclear envelope. Here we discuss known intracrine actions and argue that
      mechanisms distinct from membrane receptor activation (that is, "noncanonical"
      actions) are often operative and physiologically relevant. These actions, we
      argue, expand our understanding of peptide signaling in important ways. Moreover,
      an appreciation of noncanonical intracrine functionality informs our
      understanding of the major effector protein of the renin-angiotensin system,
      angiotensin II, as well as other hormones operative in cardiovascular biology.

PMID- 21890448
TI  - Association of self-reported race/ethnicity and genetic ancestry with arterial
      elasticity: the Multi-Ethnic Study of Atherosclerosis (MESA).
AB  - African Americans have a disproportionate burden of hypertension compared with
      white, whereas data on Hispanics is less well-defined. Mechanisms underlying
      these differences are unclear, but could be in part because of ancestral
      background and vascular function. We studied 660 African Americans and 635
      Hispanics from the Multi-Ethnic Study of Atherosclerosis (MESA) with complete
      data on genetic ancestry, pulse pressure (PP), and large and small arterial
      elasticity (LAE, SAE). LAE and SAE were obtained using the HDI PulseWave CR-2000
      Research CardioVascular Profiling Instrument. Among African Americans, higher
      European ancestry was marginally associated with higher LAE (P = .05) and lower
      PP (P = .05); results for LAE were attenuated after adjustment for potential
      mediators (P = .30). Among Hispanics, higher Native American ancestry was
      associated with higher SAE (P = .0006); higher African ancestry was marginally
      associated with lower SAE (P = .07). Ancestry was not significantly associated
      with LAE or PP in Hispanics. Among African Americans, higher European ancestry
      may be associated with less large artery damage, as measured by LAE and PP,
      although these associations warrant further study. Among Hispanics, ancestry is
      strongly associated with SAE. Future studies should consider genetic ancestry
      when studying hypertension in race/ethnic minorities, particularly among
      Hispanics.

PMID- 21890450
TI  - Conducting research with tribal communities: sovereignty, ethics, and data
      sharing issues.
AB  - BACKGROUND: When conducting research with American Indian tribes, informed
      consent beyond conventional institutional review board (IRB) review is needed
      because of the potential for adverse consequences at a community or governmental
      level that are unrecognized by academic researchers. OBJECTIVES: In this article,
      we review sovereignty, research ethics, and data-sharing considerations when
      doing community-based participatory health-related or natural-resource-related
      research with American Indian nations and present a model material and data
      sharing agreement that meets tribal and university requirements. DISCUSSION: Only
      tribal nations themselves can identify potential adverse outcomes, and they can
      do this only if they understand the assumptions and methods of the proposed
      research. Tribes must be truly equal partners in study design, data collection,
      interpretation, and publication. Advances in protection of intellectual property
      rights (IPR) are also applicable to IRB reviews, as are principles of sovereignty
      and indigenous rights, all of which affect data ownership and control.
      CONCLUSIONS: Academic researchers engaged in tribal projects should become
      familiar with all three areas: sovereignty, ethics and informed consent, and IPR.
      We recommend developing an agreement with tribal partners that reflects both
      health-related IRB and natural-resource-related IPR considerations.

PMID- 21890451
TI  - A 5-microRNA signature for lung squamous cell carcinoma diagnosis and hsa-miR-31
      for prognosis.
AB  - PURPOSE: Recent studies have suggested that microRNA biomarkers could be useful
      for stratifying lung cancer subtypes, but microRNA signatures varied between
      different populations. Squamous cell carcinoma (SCC) is one major subtype of lung
      cancer that urgently needs biomarkers to aid patient management. Here, we
      undertook the first comprehensive investigation on microRNA in Chinese SCC
      patients. EXPERIMENTAL DESIGN: MicroRNA expression was measured in cancerous and
      noncancerous tissue pairs strictly collected from Chinese SCC patients (stages I
      III), who had not been treated with chemotherapy or radiotherapy prior to
      surgery. The molecular targets of proposed microRNA were further examined.
      RESULTS: We identified a 5-microRNA classifier (hsa-miR-210, hsa-miR-182, hsa-miR
      486-5p, hsa-miR-30a, and hsa-miR-140-3p) that could distinguish SCC from normal
      lung tissues. The classifier had an accuracy of 94.1% in a training cohort (34
      patients) and 96.2% in a test cohort (26 patients). We also showed that high
      expression of hsa-miR-31 was associated with poor survival in these 60 SCC
      patients by Kaplan-Meier analysis (P = 0.007), by univariate Cox analysis (P =
      0.011), and by multivariate Cox analysis (P = 0.011). This association was
      independently validated in a separate cohort of 88 SCC patients (P = 0.008,
      0.011, and 0.003 in Kaplan-Meier analysis, univariate Cox analysis, and
      multivariate Cox analysis, respectively). We then determined that the tumor
      suppressor DICER1 is a target of hsa-miR-31. Expression of hsa-miR-31 in a human
      lung cancer cell line repressed DICER1 activity but not PPP2R2A or LATS2.
      CONCLUSIONS: Our results identified a new diagnostic microRNA classifier for SCC
      among Chinese patients and a new prognostic biomarker, hsa-miR-31.

PMID- 21890452
TI  - A phase I trial of liposomal doxorubicin, bevacizumab, and temsirolimus in
      patients with advanced gynecologic and breast malignancies.
AB  - PURPOSE: Liposomal doxorubicin (D) and bevacizumab (A) are active single agents
      in gynecologic and breast malignancies which share a resistance mechanism:
      upregulation of hypoxia inducible factor (HIF-1alpha). We, therefore, added
      temsirolimus (T), which inhibits HIF-1alpha, to D and A (DAT). Trial objectives
      were assessment of safety, preliminary efficacy, and identification of biological
      response correlates. PATIENTS AND METHODS: Cycle length was 21 days, with IV D,
      A, and T on day 1; T on days 8 and 15 (3+3 dose-escalation design with expansion
      cohorts). Mutational assays for PIK3CA, BRAF, KRAS, and immunhistochemistry for
      PTEN loss were conducted. RESULTS: This article details 74 patients with
      gynecologic and breast malignancies who received at least one dose of drug on
      study. Median patient age: 52 (27-79); prior regimens: 4 (1-11). Responses: 1
      (1.4%) complete response (CR), 14 (18.9%) partial responses (PR), and 13 (17.6%)
      with stable disease (SD) >= 6 months (total = 37.9%). The most common grade 1
      toxicities were fatigue (27%) and anemia (20.2%). Notable grade 3/4 toxicities:
      thrombocytopenia (9.5%), mucositis (6.7%), and bowel perforation (2.7%). PIK3CA
      mutations or PTEN loss were identified in 25 of 59 (42.3%) of tested patients.
      Among these, nine (36%) achieved CR/PR and four (16%) had SD >= 6 months
      (CR+PR+SD >= 6 months = 52%). CONCLUSIONS: DAT is well tolerated with manageable
      side effects. Responses observed warrant further evaluation. Mutational analyses
      were notable for a high percentage of responders with phosphoinositide-3-kinase
      pathway aberrations.

PMID- 21890453
TI  - The reconstruction of transcriptional networks reveals critical genes with
      implications for clinical outcome of multiple myeloma.
AB  - PURPOSE: The combined use of microarray technologies and bioinformatics analysis
      has improved our understanding of biological complexity of multiple myeloma (MM).
      In contrast, the application of the same technology in the attempt to predict
      clinical outcome has been less successful with the identification of
      heterogeneous molecular signatures. Herein, we have reconstructed gene regulatory
      networks in a panel of 1,883 samples from MM patients derived from publicly
      available gene expression sets, to allow the identification of robust and
      reproducible signatures associated with poor prognosis across independent data
      sets. EXPERIMENTAL DESIGN: Gene regulatory networks were reconstructed by using
      Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) and
      microarray data from seven MM data sets. Critical analysis of network components
      was applied to identify genes playing an essential role in transcriptional
      networks, which are conserved between data sets. RESULTS: Network critical
      analysis revealed that (i) CCND1 and CCND2 were the most critical genes; (ii)
      CCND2, AIF1, and BLNK had the largest number of connections shared among the data
      sets; (iii) robust gene signatures with prognostic power were derived from the
      most critical transcripts and from shared primary neighbors of the most connected
      nodes. Specifically, a critical-gene model, comprising FAM53B, KIF21B, WHSC1, and
      TMPO, and a neighbor-gene model, comprising BLNK shared neighbors CSGALNACT1 and
      SLC7A7, predicted survival in all data sets with follow-up information.
      CONCLUSIONS: The reconstruction of gene regulatory networks in a large panel of
      MM tumors defined robust and reproducible signatures with prognostic importance,
      and may lead to identify novel molecular mechanisms central to MM biology.

PMID- 21890454
TI  - Species D adenoviruses as oncolytics against B-cell cancers.
AB  - PURPOSE: Oncolytic viruses are self-amplifying anticancer agents that make use of
      the natural ability of viruses to kill cells. Adenovirus serotype 5 (Ad5) has
      been extensively tested against solid cancers, but less so against B-cell cancers
      because these cells do not generally express the coxsackie and adenoviral
      receptor (CAR). To determine whether other adenoviruses might have better
      potency, we "mined" the adenovirus virome of 55 serotypes for viruses that could
      kill B-cell cancers. EXPERIMENTAL DESIGN: Fifteen adenoviruses selected to
      represent Ad species B, C, D, E, and F were tested in vitro against cell lines
      and primary patient B-cell cancers for their ability to infect, replicate in, and
      kill these cells. Select viruses were also tested against B-cell cancer
      xenografts in immunodeficient mice. RESULTS: Species D adenoviruses mediated most
      robust killing against a range of B-cell cancer cell lines, against primary
      patient marginal zone lymphoma cells, and against primary patient CD138+ myeloma
      cells in vitro. When injected into xenografts in vivo, single treatment with
      select species D viruses Ad26 and Ad45 delayed lymphoma growth. CONCLUSIONS:
      Relatively unstudied species D adenoviruses have a unique ability to infect and
      replicate in B-cell cancers as compared with other adenovirus species. These data
      suggest these viruses have unique biology in B cells and support translation of
      novel species D adenoviruses as oncolytics against B-cell cancers.

PMID- 21890455
TI  - Toll-like receptor 9 agonist IMO cooperates with cetuximab in K-ras mutant
      colorectal and pancreatic cancers.
AB  - PURPOSE: K-Ras somatic mutations are a strong predictive biomarker for resistance
      to epidermal growth factor receptor (EGFR) inhibitors in patients with colorectal
      and pancreatic cancer. We previously showed that the novel Toll-like receptor 9
      (TLR9) agonist immunomodulatory oligonucleotide (IMO) has a strong in vivo
      activity in colorectal cancer models by interfering with EGFR-related signaling
      and synergizing with the anti-EGFR monoclonal antibody cetuximab. EXPERIMENTAL
      DESIGN: In the present study, we investigated, both in vitro and in vivo, the
      antitumor effect of IMO alone or in combination with cetuximab in subcutaneous
      colon and orthotopic pancreatic cancer models harboring K-Ras mutations and
      resistance to EGFR inhibitors. RESULTS: We showed that IMO was able to
      significantly restore the sensitivity of K-Ras mutant cancer cells to cetuximab,
      producing a marked inhibition of cell survival and a complete suppression of
      mitogen-activated protein kinase phosphorylation, when used in combination with
      cetuximab. IMO interfered with EGFR-dependent signaling, modulating the
      functional interaction between TLR9 and EGFR. In vivo, IMO plus cetuximab
      combination caused a potent and long-lasting cooperative antitumor activity in
      LS174T colorectal cancer and in orthotopic AsPC1 pancreatic cancer. The
      capability of IMO to restore cetuximab sensitivity was further confirmed by using
      K-Ras mutant colorectal cancer cell models obtained through homologous
      recombination technology. CONCLUSIONS: We showed that IMO markedly inhibits
      growth of K-Ras mutant colon and pancreatic cancers in vitro and in nude mice and
      cooperates with cetuximab via multiple mechanisms of action. Therefore, we
      propose IMO plus cetuximab as a therapeutic strategy for K-Ras wild-type as well
      for K-Ras mutant, cetuximab-resistant colorectal and pancreatic cancers.

PMID- 21890457
TI  - Bile acid-induced expression of activation-induced cytidine deaminase during the
      development of Barrett's oesophageal adenocarcinoma.
AB  - Activation-induced cytidine deaminase (AID) induces somatic mutations in various
      host genes of non-lymphoid tissues, thereby contributing to carcinogenesis. We
      recently demonstrated that Helicobacter pylori infection and/or proinflammatory
      cytokine stimulation triggers aberrant AID expression in gastric epithelial
      cells, causing mutations in the tumour-suppressor TP53 gene. The findings of the
      present study provide evidence of ectopic AID expression in Barrett's oesophagus
      and Barrett's oesophageal adenocarcinoma, a cancer that develops under chronic
      inflammatory conditions. Immunoreactivity for endogenous AID was observed in 24
      of 28 (85.7%) specimens of the columnar cell-lined Barrett's oesophagus and in 20
      of 22 (90.9%) of Barrett's adenocarcinoma, whereas weak or no AID protein
      expression was detectable in normal squamous epithelial cells of the oesophagus.
      We validated these results by analysing tissue specimens from another cohort
      comprising 16 cases with Barrett's oesophagus and four cases with Barrett's
      adenocarcinoma. In vitro treatment of human non-neoplastic oesophageal squamous
      derived cells with sodium salt deoxycholic acid induced ectopic AID expression
      via the nuclear factor-kappaB activation pathway. These findings suggest that
      aberrant AID expression occurs in a substantial proportion of Barrett's
      epithelium, at least in part due to bile acid stimulation. Considering the
      genotoxic activity of AID, our current findings suggest that aberrant AID
      expression might enhance the susceptibility to genetic alterations in Barrett's
      columnar-lined epithelial cells, leading to cancer development.

PMID- 21890456
TI  - The prognostic significance of various 13q14 deletions in chronic lymphocytic
      leukemia.
AB  - PURPOSE: To further our understanding of the biology and prognostic significance
      of various chromosomal 13q14 deletions in chronic lymphocytic leukemia (CLL).
      EXPERIMENTAL DESIGN: We analyzed data from SNP 6.0 arrays to define the anatomy
      of various 13q14 deletions in a cohort of 255 CLL patients and have correlated
      two subsets of 13q14 deletions (type I exclusive of RB1 and type II inclusive of
      RB1) with patient survival. Furthermore, we measured the expression of the 13q14
      resident microRNAs by quantitative PCR (Q-PCR) in 242 CLL patients and
      subsequently assessed their prognostic significance. We sequenced all coding
      exons of RB1 in patients with monoallelic RB1 deletion and have sequenced the
      13q14-resident miR locus in all patients. RESULTS: Large 13q14 (type II)
      deletions were detected in approximately 20% of all CLL patients and were
      associated with shortened survival. A strong association between 13q14 type II
      deletions and elevated genomic complexity, as measured through CLL-FISH or SNP
      6.0 array profiling, was identified, suggesting that these lesions may contribute
      to CLL disease evolution through genomic destabilization. Sequence and copy
      number analysis of the RB1 gene identified a small CLL subset that is RB1 null.
      Finally, neither the expression levels of the 13q14-resident microRNAs nor the
      degree of 13q14 deletion, as measured through SNP 6.0 array-based copy number
      analysis, had significant prognostic importance. CONCLUSIONS: Our data suggest
      that the clinical course of CLL is accelerated in patients with large (type II)
      13q14 deletions that span the RB1 gene, therefore justifying routine
      identification of 13q14 subtypes in CLL management.

PMID- 21890458
TI  - Small GTPase RAB45-mediated p38 activation in apoptosis of chronic myeloid
      leukemia progenitor cells.
AB  - Chronic myelogenous leukemia (CML) is characterized by a reciprocal chromosomal
      translocation (9;22) that generates the Bcr-Abl fusion gene. BCR-ABL transforming
      activity is mediated by critical downstream signaling pathways that are
      aberrantly activated by tyrosine kinases. However, the mechanisms of BCR-ABL anti
      apoptotic effects and the signaling pathways by which BCR-ABL influences
      apoptosis in BCR-ABL-expressing cells are poorly defined. In this study, we found
      that treatment with ABL kinase inhibitors or depletion of BCR-ABL induced the
      expression of RAB45 messenger RNA and protein and induced apoptosis via reduction
      of mitochondrial membrane potential and p38 activation in CML cell lines and BCR
      ABL(+) progenitor cells from CML patients. Overexpressed RAB45 induced the
      activation of caspases-3 and -9 and reduced the expression of Survivin, XIAP, c
      IAP1 and c-IAP2 in CML cells. Moreover, in colony-forming cells derived from CML
      aldehyde dehydrogenase(hi)/CD34(+) cells, treatment with ABL kinase inhibitors
      induced RAB45 expression and reduced mitochondrial membrane potential, resulting
      in inhibited colony formation of Bcr-Abl(+) progenitor cells. The overexpression
      of RAB45 significantly decreased colony numbers and induced apoptosis through the
      activation of caspases-3 and -9. Furthermore, the overexpression of RAB45
      increased the phosphorylation levels of p38, resulting in the induction of
      apoptosis and inhibition of proliferation of CML progenitor cells. Our results
      identify a new signaling molecule involved in BCR-ABL modulation of apoptosis and
      suggest that RAB45 induction strategies may have therapeutic utility in patients
      with CML.

PMID- 21890459
TI  - The inhibition of RANKL/RANK signaling by osteoprotegerin suppresses bone
      invasion by oral squamous cell carcinoma cells.
AB  - Oral squamous cell carcinomas (OSCCs) are malignant tumors that frequently invade
      the maxilla and mandibular bone. However, the molecular mechanisms underlying
      bone invasion by OSCC are unclear. Recent studies showed that receptor activator
      of nuclear factor kappaB (RANK) was expressed not only in osteoclast precursors
      but also in tumor cells. Therefore, we examined whether RANK ligand (RANKL)/RANK
      signaling regulates bone invasion by OSCC cells in vivo and in vitro. We first
      injected human OSCC B88 cells into the masseter region of nude mice. Mice were
      treated for 3 weeks with osteoprotegerin (OPG), the decoy receptor for RANKL.
      Treatment with OPG decreased bone invasion by B88 cells, reduced the number of
      osteoclasts and increased B88 cell apoptosis. However, OPG did not affect
      apoptosis and proliferation in B88 cells in vitro, suggesting that the effects of
      OPG on apoptosis in B88 cells are restricted in a bone environment. RANK was
      expressed in the B88 cells and in OSCC cells from patients. RANKL induced NF
      kappaB activation and extracellular signal-regulated kinase phosphorylation in
      B88 cells and enhanced B88 cell migration in a modified chemotaxis chamber
      equipped with a gelatin-coated filter. OPG inhibited RANKL-induced NF-kappaB
      activation, extracellular signal-regulated kinase phosphorylation and cell
      migration. Our data clearly indicate that RANKL/RANK inhibition suppresses bone
      invasion by inhibiting osteoclastogenesis and cancer cell migration and by
      inducing apoptosis of cancer cells via indirect anticancer action in vivo.

PMID- 21890460
TI  - MicroRNA-423 promotes cell growth and regulates G(1)/S transition by targeting
      p21Cip1/Waf1 in hepatocellular carcinoma.
AB  - MicroRNAs (miRNAs) are small non-coding RNA molecules that are often located in
      genomic breakpoint regions and can act as oncogenes or tumor suppressor genes in
      human cancer. Our previous study showed that microRNA-423 (miR-423), which
      localized to the frequently amplified region of chromosome 17q11, was upregulated
      in hepatocellular carcinoma (HCC). However, the potential functions and exact
      mechanistic roles of miR-423 in hepatic carcinogenesis remain unknown. Here, we
      demonstrated that miR-423 significantly promotes cell growth and cell cycle
      progression at the G(1)/S transition in HCC cells. In particular, we found that
      miR-423-3p contributes to these effects, whereas miR-423-5p does not. Further
      studies revealed that p21Cip1/Waf1 is a downstream target of miR-423 in HCC
      cells, as miR-423 bound directly to its 3' untranslated region and reduced both
      the messenger RNA and protein levels of p21Cip1/Waf1. Moreover, enforced
      expression of p21Cip1/Waf1 abrogated miR-423-induced effects on HCC cell
      proliferation and cell cycle progression. These findings indicate that miR-423
      exerts growth-promoting effects in hepatic carcinogenesis through the suppression
      of tumor suppressor p21Cip1/Waf1 expression. The results of this study define miR
      423 as a new oncogenic miRNA in HCC.

PMID- 21890469
TI  - Takotsubo cardiomyopathy in a patient with pulmonary embolism.
AB  - Takotsubo cardiomyopathy is an acute cardiac syndrome characterized by transient
      regional wall motion abnormalities of the left ventricular apex or midventricle.
      Patients often present with chest pain or dyspnoea, ST-segment elevation, and
      minor elevations of cardiac enzyme levels. Takotsubo cardiomyopathy has been
      associated with severe emotional or physical stress such as severe burns, spinal
      cord injury, subarachnoid haemorrhage, and multiple traumas. We report a case of
      takotsubo cardiomyopathy in a 79-year-old woman with pulmonary embolism. Although
      pulmonary embolism has been listed as a potential cause of takotsubo
      cardiomyopathy, this is the first case reported with this association.

PMID- 21890461
TI  - Activation of the mTOR pathway by low levels of xenoestrogens in breast
      epithelial cells from high-risk women.
AB  - Breast cancer is an estrogen-driven disease. Consequently, hormone replacement
      therapy correlates with disease incidence. However, increasing male breast cancer
      rates over the past three decades implicate additional sources of estrogenic
      exposure including wide spread estrogen-mimicking chemicals or xenoestrogens
      (XEs), such as bisphenol-A (BPA). By exposing renewable, human, high-risk donor
      breast epithelial cells (HRBECs) to BPA at concentrations that are detectable in
      human blood, placenta and milk, we previously identified gene expression profile
      changes associated with activation of mammalian target of rapamycin (mTOR)
      pathway genesets likely to trigger prosurvival changes in human breast cells. We
      now provide functional validation of mTOR activation using pairwise comparisons
      of 16 independent HRBEC samples with and without BPA exposure. We demonstrate
      induction of key genes and proteins in the PI3K-mTOR pathway--AKT1, RPS6 and
      4EBP1 and a concurrent reduction in the tumor suppressor, phosphatase and tensin
      homolog gene protein. Altered regulation of mTOR pathway proteins in BPA-treated
      HRBECs led to marked resistance to rapamycin, the defining mTOR inhibitor.
      Moreover, HRBECs pretreated with BPA, or the XE, methylparaben (MP), surmounted
      antiestrogenic effects of tamoxifen showing dose-dependent apoptosis evasion and
      induction of cell cycling. Overall, XEs, when tested in benign breast cells from
      multiple human subjects, consistently initiated specific functional changes of
      the kind that are attributed to malignant onset in breast tissue. Our
      observations demonstrate the feasibility of studying renewable human samples as
      surrogates and reinforce the concern that BPA and MP, at low concentrations
      detected in humans, can have adverse health consequences.

PMID- 21890470
TI  - Assessment of the American Society of Echocardiography-European Association of
      Echocardiography guidelines for diastolic function in patients with depressed
      ejection fraction: an echocardiographic and invasive haemodynamic study.
AB  - AIMS: There is controversy surrounding the accuracy of echo-Doppler variables,
      including early mitral inflow/mitral annular velocity (E/e'), for estimating left
      ventricular filling pressure (LVFP) in patients with depressed ejection fraction
      (EF < 50%). METHODS AND RESULTS: The American Society of Echocardiography
      European Association of Echocardiography (ASE-EAE) algorithm for diastolic
      function in depressed LVEF was retrospectively applied to a database of patients
      who underwent echocardiography <=20 min of cardiac catheterization. LV pre-atrial
      contraction pressure (pre-A) >=15 mmHg was elevated. Of 62 patients studied, the
      mean age was 53.6 +/- 10.6 years and the mean LVEF was 27.2 +/- 11.8%. The
      correlations of E/e' (R = 0.43, P = 0.0005) and E (R = 0.39, P = 0.002) with LV
      pre-A were modest, compared with pulmonary artery pressure (PAP, R = 0.69, P =
      0.0006), E/late mitral (A) velocity (R = 0.52, P < 0.0001), and mitral
      deceleration time (DT, R = -0.51, P < 0.0001). Using the ASE-ESE algorithm
      starting with E/A, E, and DT, 54 of 62 patients were accurately classified to
      predict LV pre-A >15 or <15 mmHg (sensitivity = 84%, specificity = 80%, area
      under the curve = 0.86, P < 0.001). The 6 of 6 patients with E/A < 1 and E < 50
      and the 14 of 15 (93%) patients with E/A> 2 and DT < 150 were correctly
      classified as having normal and elevated LVFP, respectively, while 34 of 41 (83%)
      patients with E/A = 1-2 or E/A<1 and E>50 cm/s were correctly classified using
      the addition of E/e' and PAP. CONCLUSION: This retrospective study shows that in
      this population with depressed LVEF, no single echo-Doppler variable had high
      accuracy for predicting LV pre-A >=15 mmHg. However, the ASE-EAE algorithm using
      multiple variables predicted LVFP with good accuracy, superior to any single echo
      Doppler variable alone.

PMID- 21890471
TI  - Impact of aortic stiffness on left ventricular function and B-type natriuretic
      peptide release in severe aortic stenosis.
AB  - AIMS: In aortic stenosis (AS), both reduced systemic arterial compliance and
      increased valvular load have been shown to contribute to impaired left
      ventricular (LV) function. However, the relationship between LV function and
      aortic stiffness has not yet been investigated. We aimed to assess the
      relationship between aortic stiffness and LV global longitudinal strain (GLS), LV
      filling pressures (E/E') and B-type natriuretic peptide (BNP) in AS. METHODS AND
      RESULTS: A comprehensive echocardiogram was performed in 48 consecutive patients
      with severe AS (<0.6 cm(2)/m(2)) and preserved LV ejection fraction (>=50%).
      Aortic stiffness index (beta) was calculated based on aortic diameters measured
      by echocardiography and blood pressure. Systemic arterial compliance (SAC) and
      valvulo-arterial impedance (Z(va)) were also determined. Aortic beta index was
      significantly correlated with Z(va) (r = 0.30, P= 0.03) and SAC (r = -0.29, P =
      0.04). GLS (r = 0.45, P = 0.001), E/E' (r = 0.48, P = 0.001) and BNP levels (r =
      0.45, P = 0.001) were significantly related to aortic beta index. No significant
      correlation was found between GLS or E/E' and SAC or Z(va). In multivariate
      regression analysis, aortic beta index remained correlated with GLS, E/E', and
      BNP levels. CONCLUSIONS: In patients with severe AS and preserved LV ejection
      fraction, independently of the valvular load, an increase in aortic rigidity, as
      assessed by aortic beta index, is independently correlated with reduced LV
      longitudinal function, increased LV filling pressures, and BNP levels.

PMID- 21890472
TI  - Proteomic analysis of Brassica stigmatic proteins following the self
      incompatibility reaction reveals a role for microtubule dynamics during pollen
      responses.
AB  - Mate selection and maintenance of genetic diversity is crucial to successful
      reproduction and species survival. Plants utilize self-incompatibility system as
      a genetic barrier to prevent self pollen from developing on the pistil, leading
      to hybrid vigor and diversity. In Brassica (canola, kale, and broccoli), an
      allele-specific interaction between the pollen SCR/SP11 (S-locus cysteine rich
      protein/S locus protein 11) and the pistil S Receptor Kinase, results in the
      activation of SRK which recruits the Arm Repeat Containing 1 (ARC1) E3 ligase to
      the proteasome. The targets of Arm Repeat Containing 1 are proposed to be
      compatibility factors, which when targeted for degradation by Arm Repeat
      Containing 1 results in pollen rejection. Despite the fact that protein
      degradation is predicted to be important for successful self-pollen rejection,
      the identity of the various proteins whose abundance is altered by the SI pathway
      has remained unknown. To identify potential candidate proteins regulated by the
      SI response, we have used the two-dimensional difference gel electrophoresis
      analysis, coupled with matrix-assisted laser desorption ionization/time of
      flight/MS. We identified 56 differential protein spots with 19 unique candidate
      proteins whose abundance is down-regulated following self-incompatible
      pollinations. The identified differentials are predicted to function in various
      pathways including biosynthetic pathways, signaling, cytoskeletal organization,
      and exocytosis. From the 19 unique proteins identified, we investigated the role
      of tubulin and the microtubule network during both self-incompatible and
      compatible pollen responses. Moderate changes in the microtubule network were
      observed with self-incompatible pollinations; however, a more distinct localized
      break-down of the microtubule network was observed during compatible
      pollinations, that is likely mediated by EXO70A1, leading to successful
      pollination.

PMID- 21890473
TI  - A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals
      widespread regulatory roles.
AB  - Post-translational modification of proteins by ubiquitin is a fundamentally
      important regulatory mechanism. However, proteome-wide analysis of endogenous
      ubiquitylation remains a challenging task, and almost always has relied on cells
      expressing affinity tagged ubiquitin. Here we combine single-step
      immunoenrichment of ubiquitylated peptides with peptide fractionation and high
      resolution mass spectrometry to investigate endogenous ubiquitylation sites. We
      precisely map 11,054 endogenous putative ubiquitylation sites (diglycine-modified
      lysines) on 4,273 human proteins. The presented data set covers 67% of the known
      ubiquitylation sites and contains 10,254 novel sites on proteins with diverse
      cellular functions including cell signaling, receptor endocytosis, DNA
      replication, DNA damage repair, and cell cycle progression. Our method enables
      site-specific quantification of ubiquitylation in response to cellular
      perturbations and is applicable to any cell type or tissue. Global quantification
      of ubiquitylation in cells treated with the proteasome inhibitor MG-132 discovers
      sites that are involved in proteasomal degradation, and suggests a nonproteasomal
      function for almost half of all sites. Surprisingly, ubiquitylation of about 15%
      of sites decreased more than twofold within four hours of MG-132 treatment,
      showing that inhibition of proteasomal function can dramatically reduce
      ubiquitylation on many sites with non-proteasomal functions. Comparison of
      ubiquitylation sites with acetylation sites reveals an extensive overlap between
      the lysine residues targeted by these two modifications. However, the crosstalk
      between these two post-translational modifications is significantly less frequent
      on sites that show increased ubiquitylation upon proteasome inhibition. Taken
      together, we report the largest site-specific ubiquitylation dataset in human
      cells, and for the first time demonstrate proteome-wide, site-specific
      quantification of endogenous putative ubiquitylation sites.

PMID- 21890474
TI  - Testing for "snowballing" hybrid incompatibilities in Solanum: impact of
      ancestral polymorphism and divergence estimates.
AB  - Two recent high-profile studies offered empirical evidence for a "snowballing"
      accumulation of postzygotic incompatibilities in Drosophila and Solanum
      (tomatoes). Here we present a reanalysis of the Solanum data that is motivated by
      population genetic principles. Specifically, the high levels of intraspecific
      nucleotide polymorphism in wild tomato species and presumably large effective
      population size throughout the divergence history of this clade imply that
      ancestral polymorphism should be taken into account when evaluating sequence
      divergence between species. Based on our reanalyses of synonymous-site divergence
      between the four focal Solanum species and a wide range of ancestral
      polymorphism, we assessed under which conditions the reported accumulation of
      seed sterility factors supports the snowball effect. Our results highlight the
      pivotal impact of levels of ancestral polymorphism and alternate divergence
      values, and they illustrate that robust tests of the snowball effect in Solanum
      require genome-wide estimates of divergence.

PMID- 21890475
TI  - Recombination gives a new insight in the effective population size and the
      history of the old world human populations.
AB  - The information left by recombination in our genomes can be used to make
      inferences on our recent evolutionary history. Specifically, the number of past
      recombination events in a population sample is a function of its effective
      population size (Ne). We have applied a method, Identifying Recombination in
      Sequences (IRiS), to detect specific past recombination events in 30 Old World
      populations to infer their Ne. We have found that sub-Saharan African populations
      have an Ne that is approximately four times greater than those of non-African
      populations and that outside of Africa, South Asian populations had the largest
      Ne. We also observe that the patterns of recombinational diversity of these
      populations correlate with distance out of Africa if that distance is measured
      along a path crossing South Arabia. No such correlation is found through a Sinai
      route, suggesting that anatomically modern humans first left Africa through the
      Bab-el-Mandeb strait rather than through present Egypt.

PMID- 21890476
TI  - Parallel duplication and partial subfunctionalization of beta-catenin/armadillo
      during insect evolution.
AB  - beta-Catenin is a multifunctional scaffolding protein with roles in Wnt
      signaling, cell adhesion, and centrosome separation. Here, we report on
      independent duplications of the insect beta-Catenin ortholog armadillo (arm) in
      the red flour beetle Tribolium castaneum and the pea aphid Acyrthosiphon pisum.
      Detailed sequence analysis shows that in both species, one paralog lost critical
      residues of the alpha-Catenin binding domain, which is essential for cell
      adhesion, and accumulated a dramatically higher number of amino acid
      substitutions in the central Arm repeat domain. Residues associated with aspects
      of Wnt signaling, however, are conserved in both paralogs. Consistent with these
      molecular signatures, the effects of specific and combinatorial knockdown
      experiments in the Tribolium embryo indicate that the duplication resulted in
      redundant involvement in Wnt signaling of both beta-Catenin paralogs but
      differential inheritance of the ancestral cell adhesion and centrosome separation
      functions. We conclude that the duplicated pea aphid and flour beetle beta
      catenin genes experienced partial subfunctionalization, which appears to be
      evolutionarily favored. Providing first evidence of genetic separability of the
      cell adhesion and centrosome separation functions, the duplicated Tribolium and
      Acyrthosiphon arm paralogs offer new inroads for context-specific analyses of
      beta-Catenin. Our data also revealed the conservation of a C-terminally truncated
      Arm isoform in both singleton and duplicated homologs, suggesting an as yet
      unexplored role in Wnt signaling.

PMID- 21890477
TI  - An early divergence of KhoeSan ancestors from those of other modern humans is
      supported by an ABC-based analysis of autosomal resequencing data.
AB  - Sub-Saharan Africa has consistently been shown to be the most genetically diverse
      region in the world. Despite the fact that a substantial portion of this
      variation is partitioned between groups practicing a variety of subsistence
      strategies and speaking diverse languages, there is currently no consensus on the
      genetic relationships of sub-Saharan African populations. San (a subgroup of
      KhoeSan) and many Pygmy groups maintain hunter-gatherer lifestyles and cluster
      together in autosomal-based analysis, whereas non-Pygmy Niger-Kordofanian
      speakers (non-Pygmy NKs) predominantly practice agriculture and show substantial
      genetic homogeneity despite their wide geographic range throughout sub-Saharan
      Africa. However, KhoeSan, who speak a set of relatively unique click-based
      languages, have long been thought to be an early branch of anatomically modern
      humans based on phylogenetic analysis. To formally test models of divergence
      among the ancestors of modern African populations, we resequenced a sample of
      San, Eastern, and Western Pygmies and non-Pygmy NKs individuals at 40 nongenic
      (~2 kb) regions and then analyzed these data within an Approximate Bayesian
      Computation (ABC) framework. We find substantial support for a model of an early
      divergence of KhoeSan ancestors from a proto-Pygmy-non-Pygmy NKs group ~110
      thousand years ago over a model incorporating a proto-KhoeSan-Pygmy hunter
      gatherer divergence from the ancestors of non-Pygmy NKs. The results of our
      analyses are consistent with previously identified signals of a strong bottleneck
      in Mbuti Pygmies and a relatively recent expansion of non-Pygmy NKs. We also
      develop a number of methodologies that utilize "pseudo-observed" data sets to
      optimize our ABC-based inference. This approach is likely to prove to be an
      invaluable tool for demographic inference using genome-wide resequencing data.

PMID- 21890478
TI  - Mitochondrial-nuclear interactions and accelerated compensatory evolution:
      evidence from the primate cytochrome C oxidase complex.
AB  - Accelerated rates of mitochondrial protein evolution have been proposed to
      reflect Darwinian coadaptation for efficient energy production for mammalian
      flight and brain activity. However, several features of mammalian mtDNA (absence
      of recombination, small effective population size, and high mutation rate)
      promote genome degradation through the accumulation of weakly deleterious
      mutations. Here, we present evidence for "compensatory" adaptive substitutions in
      nuclear DNA- (nDNA) encoded mitochondrial proteins to prevent fitness decline in
      primate mitochondrial protein complexes. We show that high mutation rate and
      small effective population size, key features of primate mitochondrial genomes,
      can accelerate compensatory adaptive evolution in nDNA-encoded genes. We combine
      phylogenetic information and the 3D structure of the cytochrome c oxidase (COX)
      complex to test for accelerated compensatory changes among interacting sites.
      Physical interactions among mtDNA- and nDNA-encoded components are critical in
      COX evolution; amino acids in close physical proximity in the 3D structure show a
      strong tendency for correlated evolution among lineages. Only nuclear-encoded
      components of COX show evidence for positive selection and adaptive nDNA-encoded
      changes tend to follow mtDNA-encoded amino acid changes at nearby sites in the 3D
      structure. This bias in the temporal order of substitutions supports compensatory
      weak selection as a major factor in accelerated primate COX evolution.

PMID- 21890479
TI  - Tail paradox, partial identifiability, and influential priors in Bayesian branch
      length inference.
AB  - Recent studies have observed that Bayesian analyses of sequence data sets using
      the program MrBayes sometimes generate extremely large branch lengths, with
      posterior credibility intervals for the tree length (sum of branch lengths)
      excluding the maximum likelihood estimates. Suggested explanations for this
      phenomenon include the existence of multiple local peaks in the posterior, lack
      of convergence of the chain in the tail of the posterior, mixing problems, and
      misspecified priors on branch lengths. Here, we analyze the behavior of Bayesian
      Markov chain Monte Carlo algorithms when the chain is in the tail of the
      posterior distribution and note that all these phenomena can occur. In Bayesian
      phylogenetics, the likelihood function approaches a constant instead of zero when
      the branch lengths increase to infinity. The flat tail of the likelihood can
      cause poor mixing and undue influence of the prior. We suggest that the main
      cause of the extreme branch length estimates produced in many Bayesian analyses
      is the poor choice of a default prior on branch lengths in current Bayesian
      phylogenetic programs. The default prior in MrBayes assigns independent and
      identical distributions to branch lengths, imposing strong (and unreasonable)
      assumptions about the tree length. The problem is exacerbated by the strong
      correlation between the branch lengths and parameters in models of variable rates
      among sites or among site partitions. To resolve the problem, we suggest two
      multivariate priors for the branch lengths (called compound Dirichlet priors)
      that are fairly diffuse and demonstrate their utility in the special case of
      branch length estimation on a star phylogeny. Our analysis highlights the need
      for careful thought in the specification of high-dimensional priors in Bayesian
      analyses.

PMID- 21890480
TI  - Estimating the basic reproductive number from viral sequence data.
AB  - Epidemiological processes leave a fingerprint in the pattern of genetic structure
      of virus populations. Here, we provide a new method to infer epidemiological
      parameters directly from viral sequence data. The method is based on phylogenetic
      analysis using a birth-death model (BDM) rather than the commonly used coalescent
      as the model for the epidemiological transmission of the pathogen. Using the BDM
      has the advantage that transmission and death rates are estimated independently
      and therefore enables for the first time the estimation of the basic reproductive
      number of the pathogen using only sequence data, without further assumptions like
      the average duration of infection. We apply the method to genetic data of the HIV
      1 epidemic in Switzerland.

PMID- 21890481
TI  - Cognitive decline in the elderly: an analysis of population heterogeneity.
AB  - BACKGROUND: studies of cognitive ageing at the group level suggest that age is
      associated with cognitive decline; however, there may be individual differences
      such that not all older adults will experience cognitive decline. OBJECTIVE: to
      evaluate patterns of cognitive decline in a cohort of older adults initially free
      of dementia. DESIGN, SETTING AND SUBJECTS: elderly Catholic clergy members
      participating in the Religious Orders Study were followed for up to 15 years.
      Cognitive performance was assessed annually. METHODS: performance on a composite
      global measure of cognition was analysed using random effects models for baseline
      performance and change over time. A profile mixture component was used to
      identify subgroups with different cognitive trajectories over the study period.
      RESULTS: from a sample of 1,049 participants (mean age 75 years), three subgroups
      were identified based on the distribution of baseline performance and change over
      time. The majority (65%) of participants belonged to a slow decline class that
      did not experience substantial cognitive decline over the observation period [
      0.04 baseline total sample standard deviation (SD) units/year]. About 27%
      experienced moderate decline (-0.19 SD/year), and 8% belonged to a class
      experiencing rapid decline (-0.57 SD/year). A subsample analysis revealed that
      when substantial cognitive decline does occur, the magnitude and rate of decline
      is correlated with neuropathological processes. CONCLUSIONS: in this sample, the
      most common pattern of cognitive decline is extremely slow, perceptible on a time
      scale measured by decades, not years. While in need of cross validation, these
      findings suggest that cognitive changes associated with ageing may be minimal and
      emphasise the importance of understanding the full range of age-related
      pathologies that may diminish brain function.

PMID- 21890482
TI  - 'There's a hell of a noise': living with a hearing loss in residential care.
AB  - BACKGROUND: Hearing loss is common in older age. Research with older people in
      residential care settings has identified high prevalence of hearing loss and low
      uptake of hearing aids. Hearing loss in these settings is associated with reduced
      social engagement. Although hearing aids remain the default treatment for
      presbyacusic hearing loss, these are not well used. We do not know what other
      modifiable factors contribute to communication problems for older people with
      hearing loss living in residential care. OBJECTIVES: To explore the factors
      affecting communicating with a hearing loss in residential care. METHODS: An
      ethnographic study in two residential care homes comprised 19 sessions of
      observation, and in-depth interviews with 18 residents. Observations explored
      communication behaviour in everyday interactions, including mealtimes, structured
      groups and informal group activities. Interviews were informed by the
      observations and identified reasons for these behaviours and communication
      preferences. Observational data were recorded in field notes and interviews were
      audio-recorded and transcribed. Analysis was conducted using constant comparison
      methods. RESULTS: Hearing loss affected whether residents were able to access
      social opportunities. Two key themes influenced this (i) contextual issues
      compounded communication difficulties and (ii) environmental noise restricted the
      residents' communication choices. Problems were observed at every mealtime and
      during formal and informal group activities. The use of hearing aids and access
      to hearing services did not improve social engagement. CONCLUSIONS: Environmental
      and social factors are key to maximising communication opportunities.
      Improvements to communication in residential care settings could be based on
      changes in these with input from residents and staff. Further work is needed to
      develop effective communication strategies in residential care.

PMID- 21890483
TI  - The prevalence of mental health problems among older adults admitted as an
      emergency to a general hospital.
AB  - BACKGROUND: A high prevalence of co-morbid mental health problems is reported
      among older adults admitted to general hospitals. SETTING: An 1,800 bed teaching
      hospital. DESIGN: Consecutive general medical and trauma orthopaedic admissions
      aged 70 or older were screened for mental health problems. Those screening
      positive were invited to undergo further assessment, and were interviewed to
      complete a battery of health status measurements. RESULTS: Of 1,004 patients
      screened, 36% had no mental health problems or had anxiety alone. Of those
      screening positive 250 took part in the full study. Adjusting for the two-stage
      sampling design, 50% of admitted patients over 70 were cognitively impaired, 27%
      had delirium and 8-32% were depressed. Six percent had hallucinations, 8%
      delusions, 21% apathy and 9% agitation/aggression (of at least moderate
      severity). Of those with mental health problems, 47% were incontinent, 49% needed
      help with feeding and 44% needed major help to transfer. INTERPRETATION: We
      confirm the high prevalence of mental health problems among older adults admitted
      to general hospitals. These patients have high levels of functional dependency,
      psychological and behavioural problems which have implications for how they are
      cared for. Services that identify these problems and offer therapeutic
      intervention should be evaluated.

PMID- 21890484
TI  - Why drivers start drinking and driving--a prospective study over a 6-year period
      in the GAZEL cohort.
AB  - AIMS: To estimate the frequency with which a group of formerly safe drivers adopt
      driving while alcohol-intoxicated (DWI), and to determine the factors associated
      with DWI adoption. METHODS: Participants were current employees or recent
      retirees of the French national electricity and gas company. An annual cohort
      questionnaire that includes two questions about overall alcohol consumption is
      sent each year to participants. A Driving Behaviour and Road Safety (DBRS)
      questionnaire was administered in 2001, 2004 and 2007. Only drivers who
      participated in the 2001 survey received the 2004 and 2007 questionnaires.
      RESULTS: More than 462 participants ceased DWI between 2001 and 2007, while 511
      adopted this behaviour for the first time. Multivariate analysis showed that the
      risk of adopting DWI was associated with male gender and with several changes
      over the preceding years: increased alcohol consumption, increased number of
      close friends, decreased number of close relatives and decreased attitudes in
      favour of strict enforcement/regulations. CONCLUSION: A large number of offenders
      stopped DWI between 2001 and 2007, concomitantly with an increased crackdown on
      road violations in France. But this success was compromised by the occurrence of
      new drunk drivers. Preventive strategies should target factors that facilitate
      DWI adoption-in particular, increased alcohol consumption and low acceptance of
      law enforcement initiatives.

PMID- 21890485
TI  - Clinical experience with baclofen in the management of alcohol-dependent patients
      with psychiatric comorbidity: a selected case series.
AB  - AIMS: To illustrate the potential indications for, and adverse effects of,
      baclofen pharmacotherapy for alcohol dependence in patients with co-existing
      psychiatric illness. METHODS: Audit of the files of alcohol-dependent patients
      treated for comorbid non-psychotic psychiatric illness in a specialist
      detoxification unit with integrated outpatient treatment. Files were selected of
      patients who had been offered treatment with baclofen because other alcohol
      pharmacotherapies had previously been unsuccessful in preventing relapse or were
      contraindicated. RESULTS: Of the 21 selected patients, 13 attended for outpatient
      treatment, with follow-up periods ranging from 4 days to 27 months, and the
      outcomes could be rated. Prescribed baclofen doses ranged from 30 to 275 mg
      daily. Common side effects at lower doses included tiredness and sedation; one
      patient on 120 mg/day developed reversible severe back pain, and a patient taking
      up to 275 mg/day developed somnolence, dizziness and incontinence. Seven patients
      maintained significant periods of abstinence, and one patient reduced daily
      consumption to non-problematic levels. Two patients consumed an overdose of other
      central nervous system (CNS) depressants, while taking baclofen in the first week
      of treatment, were briefly unwell, were given emergency monitoring, but made a
      full recovery. CONCLUSION: While more than half the patients reported significant
      reduction in alcohol use, it is not possible to draw definite conclusions about
      the effectiveness of baclofen, given that it was combined with other psychiatric
      and alcohol treatments, and because there was no control or comparison group. We
      recommend caution when offering baclofen to patients with a history of recurrent
      overdosing or a history of other substance misuse. When prescribing in
      conjunction with other medications with CNS depressant action, close monitoring
      is recommended at initiation and during dose escalation.

PMID- 21890486
TI  - Letter from Russia: child abuse and alcohol misuse in a victim.

PMID- 21890487
TI  - Evidence for progenitor-derivative speciation in sexually deceptive orchids.
AB  - BACKGROUND AND AIMS: Sexually deceptive orchids of the genus Ophrys use mimicry
      of pollinator females to attract specific pollinators. Pollinator shifts may
      drive speciation in Ophrys, since novel pollinators may in principle act as
      isolating factors immediately. It is thus possible that evolution of novel
      species occurs rapidly and with a progenitor-derivative pattern. The aims of this
      study are to compare genetic structure and diversity among widespread and
      geographically restricted Ophrys taxa, to test whether genetic structure is
      associated with specific pollinators, and to investigate whether any widespread
      species may have acted as a progenitor for the evolution of more restricted taxa.
      METHODS: Genetic differentiation and diversity were investigated in O. leucadica
      and O. cinereophila, the two taxa of the Ophrys fusca sensu lato complex
      widespread in the Aegean, and three geographically restricted taxa from Rhodes,
      O. attaviria, O. parvula and O. persephonae, all differing in their specific
      pollinators. This was done using amplified fragment length polymorphism (AFLP)
      DNA fingerprinting, and sequencing of the low-copy nuclear gene LEAFY (LFY). KEY
      RESULTS: All taxa were found to be separate genetic entities, with O. leucadica
      forming two geographic groups from the west and east of the Aegean. Genetic
      structure was significantly shaped by pollinators and geography, and comparison
      of sequence and AFLP data revealed ancestral polymorphisms shared among several
      taxa. Among the sampled taxa, O. leucadica harbours the greatest genetic
      differentiation and geographic structure, and the highest genetic diversity. Part
      of the genome of O. parvula, endemic to Rhodes, may be derived from O. leucadica.
      CONCLUSIONS: Pollinators probably influence the genetic structure of the
      investigated Ophrys species. The genetic pattern identified is consistent with O.
      leucadica being the oldest of the sampled taxa, making O. leucadica a candidate
      progenitor species from which more restricted taxa such as O. parvula may have
      evolved.

PMID- 21890488
TI  - Primary angioplasty in acute myocardial infarction with right bundle branch
      block: should new onset right bundle branch block be added to future guidelines
      as an indication for reperfusion therapy?
AB  - AIMS: The current guidelines recommend reperfusion therapy in acute myocardial
      infarction (AMI) with ST-segment elevation or left bundle branch block (LBBB).
      Surprisingly, the right bundle branch block (RBBB) is not listed as an indication
      for reperfusion therapy. This study analysed patients with AMI presenting with
      RBBB [with or without left anterior hemiblock (LAH) or left posterior hemiblock
      (LPH)] and compared them with those presenting with LBBB or with other
      electrocardiographic (ECG) patterns. The aim was to describe angiographic
      patterns and primary angioplasty use in AMI patients with RBBB. METHODS AND
      RESULTS: A cohort of 6742 patients with AMI admitted to eight participating
      hospitals was analysed. Baseline clinical characteristics, ECG patterns, coronary
      angiographic, and echocardiographic data were correlated with the reperfusion
      therapies used and with in-hospital outcomes. Right bundle branch block was
      present in 6.3% of AMI patients: 2.8% had RBBB alone, 3.2% had RBBB + LAH, and
      0.3% had RBBB + LPH. TIMI flow 0 in the infarct-related artery was present in
      51.7% of RBBB patients vs. 39.4% of LBBB patients (P = 0.023). Primary
      percutaneous coronary intervention (PCI) was performed in 80.1% of RBBB patients
      vs. 68.3% of LBBB patients (P< 0.001). In-hospital mortality of RBBB patients was
      similar to LBBB (14.3 vs. 13.1%, P = 0.661). Patients with new or presumably new
      blocks had the highest (LBBB 15.8% and RBBB 15.4%) incidence of cardiogenic shock
      from all ECG subgroups. Percutaneous coronary intervention was done more
      frequently (84.8%) in patients with new or presumably new RBBB when compared with
      other patients with blocks (old RBBB 66.0%, old LBBB 62.3%, new or presumably new
      LBBB 73.0%). In-hospital mortality was highest (18.8%) among patients presenting
      with new or presumably new RBBB, followed by new or presumably new LBBB (13.2%),
      old LBBB (10.1%), and old RBBB (6.4%). Among 35 patients with acute left main
      coronary artery occlusion, 26% presented with RBBB (mostly with LAH) on the
      admission ECG. CONCLUSION: Acute myocardial infarction with RBBB is frequently
      caused by the complete occlusion of the infarct-related artery and is more
      frequently treated with primary PCI when compared with AMI + LBBB. In-hospital
      mortality of patients with AMI and RBBB is highest from all ECG presentations of
      AMI. Restoration of coronary flow by primary PCI may lead to resolution of the
      conduction delay on the discharge ECG. Right bundle branch block should strongly
      be considered for listing in future guidelines as a standard indication for
      reperfusion therapy, in the same way as LBBB.

PMID- 21890490
TI  - KDM6B/JMJD3 histone demethylase is induced by vitamin D and modulates its effects
      in colon cancer cells.
AB  - KDM6B/JMJD3 is a histone H3 lysine demethylase with an important gene regulatory
      role in development and physiology. Here, we show that human JMJD3 expression is
      induced by the active vitamin D metabolite 1alpha,25-dihydroxyvitamin D(3)
      (1,25(OH)(2)D(3)) and that JMJD3 modulates the gene regulatory action of this
      hormone. 1,25(OH)(2)D(3) activates the JMJD3 gene promoter and increases the
      level of JMJD3 RNA in human cancer cells. JMJD3 upregulation was strictly
      dependent on vitamin D receptor (VDR) expression and was abolished by
      cycloheximide. In SW480-ADH colon cancer cells, JMJD3 knockdown or expression of
      an inactive mutant JMJD3 fragment decreased the induction by 1,25(OH)(2)D(3) of
      several target genes and of an epithelial adhesive phenotype. Moreover, JMJD3
      knockdown upregulated the epithelial-to-mesenchymal transition inducers SNAIL1
      and ZEB1 and the mesenchymal markers fibronectin and LEF1, while it downregulated
      the epithelial proteins E-cadherin, Claudin-1 and Claudin-7. Additionally, JMJD3
      knockdown abolished the nuclear export of beta-catenin and the inhibition of beta
      catenin transcriptional activity caused by 1,25(OH)(2)D(3). Importantly, the
      expression of JMJD3 correlated directly with that of VDR and inversely with that
      of SNAI1 in a series of 96 human colon tumours. Our results indicate for the
      first time that an epigenetic gene coding for a histone demethylase such as JMJD3
      is a VDR co-target that partially mediates the effects of 1,25(OH)(2)D(3) on
      human colon.

PMID- 21890491
TI  - Keratin disorders: from gene to therapy.
AB  - The term 'keratin' is generally accepted to refer to the epithelial keratins of
      soft and hard epithelial tissues such as: skin, cornea, hair and nail. Since
      their initial characterization, the total number of mammalian keratins has
      increased to 54, including 28 type I and 26 type II keratins. Inherited defects
      that weaken the keratin load-bearing cytoskeleton produce phenotypes
      characterized by fragility of specific subsets of epithelial tissues. The vast
      majority of mutations are either missense or small in-frame in-del mutations and
      disease severity often relates to the position of the mutation in relation to the
      rod domain. The most complex epithelial structure in humans, the hair follicle,
      contains trichocyte ('hard') keratin filaments and approximately half of the 54
      functional human keratin genes are trichocyte keratins. So far, only four of
      these have been linked to human genetic disorders: monilethrix, hair-nail
      ectodermal dysplasia, pseudofolliculitis barbae and woolly hair, while the
      majority of the hair keratins remain unlinked to human phenotypes. Keratin
      disorders are a classical group of dominant-negative genetic disorders,
      representing a large healthcare burden, especially within dermatology. Recent
      advances in RNA interference therapeutics, particularly in the form of small
      interfering RNAs, represent a potential therapy route for keratin disorders
      through selectively silencing the mutant allele. To date, mutant-specific siRNAs
      for epidermolysis bullosa simplex, pachyonychia congenita and Messmann epithelial
      corneal dystrophy-causing missense mutations have been developed and proven to
      have unprecedented specificity and potency. This could herald the dawn of a new
      era in translational medical research applied to genetics.

PMID- 21890489
TI  - Nitric oxide synthases: regulation and function.
AB  - Nitric oxide (NO), the smallest signalling molecule known, is produced by three
      isoforms of NO synthase (NOS; EC 1.14.13.39). They all utilize l-arginine and
      molecular oxygen as substrates and require the cofactors reduced nicotinamide
      adenine-dinucleotide phosphate (NADPH), flavin adenine dinucleotide (FAD), flavin
      mononucleotide (FMN), and (6R-)5,6,7,8-tetrahydrobiopterin (BH(4)). All NOS bind
      calmodulin and contain haem. Neuronal NOS (nNOS, NOS I) is constitutively
      expressed in central and peripheral neurons and some other cell types. Its
      functions include synaptic plasticity in the central nervous system (CNS),
      central regulation of blood pressure, smooth muscle relaxation, and
      vasodilatation via peripheral nitrergic nerves. Nitrergic nerves are of
      particular importance in the relaxation of corpus cavernosum and penile erection.
      Phosphodiesterase 5 inhibitors (sildenafil, vardenafil, and tadalafil) require at
      least a residual nNOS activity for their action. Inducible NOS (NOS II) can be
      expressed in many cell types in response to lipopolysaccharide, cytokines, or
      other agents. Inducible NOS generates large amounts of NO that have cytostatic
      effects on parasitic target cells. Inducible NOS contributes to the
      pathophysiology of inflammatory diseases and septic shock. Endothelial NOS (eNOS,
      NOS III) is mostly expressed in endothelial cells. It keeps blood vessels
      dilated, controls blood pressure, and has numerous other vasoprotective and anti
      atherosclerotic effects. Many cardiovascular risk factors lead to oxidative
      stress, eNOS uncoupling, and endothelial dysfunction in the vasculature.
      Pharmacologically, vascular oxidative stress can be reduced and eNOS
      functionality restored with renin- and angiotensin-converting enzyme-inhibitors,
      with angiotensin receptor blockers, and with statins.

PMID- 21890492
TI  - Mitochondrial respiratory complex I dysfunction promotes tumorigenesis through
      ROS alteration and AKT activation.
AB  - Previously, we have shown that a heteroplasmic mutation in mitochondrial DNA
      encoded complex I ND5 subunit gene resulted in an enhanced tumorigenesis through
      increased resistance to apoptosis. Here we report that the tumorigenic phenotype
      associated with complex I dysfunction could be reversed by introducing a yeast
      NADH quinone oxidoreductase (NDI1) gene. The NDI1 mediated electron transfer from
      NADH to Co-Q, bypassed the defective complex I and restored oxidative
      phosphorylation in the host cells. Alternatively, suppression of complex I
      activity by a specific inhibitor, rotenone or induction of oxidative stress by
      paraquat led to an increase in the phosphorylation of v-AKT murine thymoma viral
      oncogene (AKT) and enhanced the tumorigenesis. On the other hand, antioxidant
      treatment can ameliorate the reactive oxygen species-mediated AKT activation and
      reverse the tumorigenicity of complex I-deficient cells. Our results suggest that
      complex I defects could promote tumorigenesis through induction of oxidative
      stress and activation of AKT pathway.

PMID- 21890494
TI  - Combined deficiency of alpha and epsilon sarcoglycan disrupts the cardiac
      dystrophin complex.
AB  - Cardiomyopathy is a puzzling complication in addition to skeletal muscle
      pathology for patients with mutations in beta-, gamma- or delta-sarcoglycan (SG)
      genes. Patients with mutations in alpha-SG rarely have associated cardiomyopathy,
      or their cardiac pathology is very mild. We hypothesize that a fifth SG, epsilon
      SG, may compensate for alpha-SG deficiency in the heart. To investigate the
      function of epsilon-SG in striated muscle, we generated an Sgce-null mouse and a
      Sgca-;Sgce-null mouse, which lacks both alpha- and epsilon-SGs. While Sgce-null
      mice showed a wild-type phenotype, with no signs of muscular dystrophy or heart
      disease, the Sgca-;Sgce-null mouse developed a progressive muscular dystrophy and
      a more anticipated and severe cardiomyopathy. It shows a complete loss of
      residual SGs and a strong reduction in both dystrophin and dystroglycan. Our data
      indicate that epsilon-SG is important in preventing cardiomyopathy in alpha-SG
      deficiency.

PMID- 21890495
TI  - Multi-ethnic studies in complex traits.
AB  - The successes of genome-wide association (GWA) studies have mainly come from
      studies performed in populations of European descent. Since complex traits are
      characterized by marked genetic heterogeneity, the findings so far may provide an
      incomplete picture of the genetic architecture of complex traits. However, the
      recent GWA studies performed on East Asian populations now allow us to globally
      assess the heterogeneity of association signals between populations of European
      ancestry and East Asians, and the possible obstacles for multi-ethnic GWA
      studies. We focused on four different traits that represent a broad range of
      complex phenotypes, which have been studied in both Europeans and East Asians:
      type 2 diabetes, systemic lupus erythematosus, ulcerative colitis and height. For
      each trait, we observed that most of the risk loci identified in East Asians were
      shared with Europeans. However, we also observed that a significant part of the
      association signals at these shared loci seems to be independent between
      populations. This suggests that disease aetiology is common between populations,
      but that risk variants are often population specific. These variants could be
      truly population specific and result from natural selection, genetic drift and
      recent mutations, or they could be spurious, caused by the limitations of the
      method of analysis employed in the GWA studies. We therefore propose a three
      stage framework for multi-ethnic GWA analyses, starting with the commonly used
      single-nucleotide polymorphism-based analysis, and followed by a gene-based
      approach and a pathway-based analysis, which will take into account the
      heterogeneity of association between populations at different levels.

PMID- 21890496
TI  - Therapeutic value of prenatal rapamycin treatment in a mouse brain model of
      tuberous sclerosis complex.
AB  - Epileptic seizures, particularly infantile spasms, are often seen in infants with
      tuberous sclerosis complex (TSC) soon after birth. It is feared that there are
      long-term developmental and cognitive consequences from ongoing, frequent
      epilepsy. In addition, the hallmark brain pathology of TSC, cortical tubers and
      giant cells are fully developed at late gestational ages. These observations have
      led us to examine the benefit of prenatal rapamycin in a new fetal brain model of
      TSC. In this Tsc1(cc) Nes-cre(+) mouse model, recombination and loss of Tsc1 in
      neural progenitor cells leads to brain enlargement, hyperactivation of mTOR, and
      neonatal death on P0 due to reduced pup-maternal interaction. A single dose of
      prenatal rapamycin given to pregnant dams (1 mg/kg, subcutaneous) rescued the
      lethality of mutant mice. This one dose of prenatal rapamycin treatment reduced
      hyperactivation of the mTOR pathway in the mutant brain without causing apparent
      pregnancy loss. Continued postnatal rapamycin beginning at day 8 extended the
      survival of these mice to a median of 12 days with complete suppression of
      hyperactive mTOR. However, the rapamycin-treated mutants developed enlarged
      brains with an increased number of brain cells, displaying marked runting and
      developmental delay. These observations demonstrate the therapeutic benefit and
      limitations of prenatal rapamycin in a prenatal-onset brain model of TSC. Our
      data also suggest the possibility and limitations of this approach for TSC
      infants and mothers.

PMID- 21890497
TI  - The 2-thiouridylase function of the human MTU1 (TRMU) enzyme is dispensable for
      mitochondrial translation.
AB  - MTU1 (TRMU) is a mitochondrial enzyme responsible for the 2-thiolation of the
      wobble U in tRNA(Lys), tRNA(Glu) and tRNA(Gln), a post-transcriptional
      modification believed to be important for accurate and efficient synthesis of the
      13 respiratory chain subunits encoded by mtDNA. Mutations in MTU1 are associated
      with acute infantile liver failure, and this has been ascribed to a transient
      lack of cysteine, the sulfur donor for the thiouridylation reaction, resulting in
      a mitochondrial translation defect during early development. A mutation in
      tRNA(Lys) that causes myoclonic epilepsy with ragged-red fibers (MERRF) is also
      reported to prevent modification of the wobble U. Here we show that mitochondrial
      translation is unaffected in fibroblasts from an MTU1 patient, in which MTU1 is
      undetectable by immunoblotting, despite the severe reduction in the 2-thiolation
      of mitochondrial tRNA(Lys), tRNA(Glu) and tRNA(Gln). The only respiratory chain
      abnormality that we could observe in these cells was an accumulation of a Complex
      II assembly intermediate, which, however, did not affect the level of the fully
      assembled enzyme. The identical phenotype was observed by siRNA-mediated
      knockdown of MTU1 in HEK 293 cells. Further, the mitochondrial translation
      deficiencies present in myoblasts from mitochondrial encephalomyopathy, lactic
      acidosis and stroke-like episode and MERRF patients, which are associated with
      defects in post-transcriptional modification of mitochondrial tRNAs, did not
      worsen following knockdown of MTU1 in these cells. This study demonstrates that
      MTU1 is not required for mitochondrial translation at normal steady-state levels
      of tRNAs, and that it may possess an as yet uncharacterized function in another
      sulfur-trafficking pathway.

PMID- 21890499
TI  - Effects of limited and excess protein intakes of pregnant gilts on carcass
      quality and cellular properties of skeletal muscle and subcutaneous adipose
      tissue in fattening pigs.
AB  - The aim of this study was to investigate whether dietary protein intake of gilts
      during gestation below (50%) or above (250%) recommendations affects body
      composition, carcass and meat quality, and properties of skeletal muscle and
      subcutaneous adipose tissue (SCAT) in offspring at d 83 and 188 of age. German
      Landrace gilts were fed isoenergetic gestation diets (~13.7 MJ of ME/kg)
      containing a low (LP, 6.5%; n = 18), an adequate (AP, 12.1%; n = 20), or a high
      (HP, 30%; n = 16) protein content from mating until farrowing. Within 48 h of
      birth, offspring were cross-fostered to sows fed a standard diet. On d 83 of age,
      no effects of the LP diet on BW and body composition were detected, whereas HP
      pigs showed a slight growth delay (P = 0.06) associated with increased relative
      weights of small intestine (P < 0.01) and brain (P = 0.08), and reduced relative
      thymus weight (P < 0.01). On d 188 of age, BW was not different among the dietary
      groups. However, the carcass of LP pigs contained less (P = 0.01) lean and more
      (P = 0.07) fat compared with AP and HP pigs, which was only pronounced in pigs
      originating from large litters (P < 0.05). Like skeletal muscles (P = 0.06), the
      heart muscle weighed less (P = 0.02) in LP than AP pigs. Compared with AP pigs,
      LP pigs exhibited a fewer (P = 0.09) total number of myofibers in semitendinosus
      muscle plus LM both at d 83 and 188 of age, whereas total muscular DNA was less
      (P = 0.02) at d 188 only. The mRNA abundance of IGF2 measured on d 188 was
      reduced in SCAT (P = 0.03) and LM (P = 0.07) of LP compared with AP pigs. No
      changes in muscular fiber type frequency, capillary density, or creatine kinase
      activity, as well as SCAT adipocyte size and number, were observed at either
      stages of age. Meat quality characteristics remained unchanged at d 83, whereas
      Warner-Bratzler shear force value in LM was decreased (P = 0.03) in LP compared
      with AP pigs on d 188 of age. The results suggest that the maternal LP diet
      impairs prenatal myofiber formation, reduces the potential of postnatal lean
      growth related to reduced IGF2 mRNA expression and myonuclear accumulation, and
      consequently changes carcass quality toward reduced lean proportion and improved
      tenderness at market weight. In contrast, except for a slight transient growth
      delay, excess dietary protein during gestation seems to have little effect on the
      fetal programming of postnatal muscle and adipose tissue phenotype of the
      progeny.

PMID- 21890498
TI  - A valid mouse model of AGRIN-associated congenital myasthenic syndrome.
AB  - Congenital myasthenic syndromes (CMS) are inherited diseases affecting the
      neuromuscular junction (NMJ). Mutations in AGRIN (AGRN) and other genes in the
      AGRIN signaling pathway cause CMS, and gene targeting studies in mice confirm the
      importance of this pathway for NMJ formation. However, these mouse mutations are
      complete loss-of-function alleles that result in an embryonic failure of NMJ
      formation, and homozygous mice do not survive postpartum. Therefore, mouse models
      of AGRIN-related CMS that would allow preclinical testing or studies of postnatal
      disease progression are lacking. Using chemical mutagenesis in mice, we
      identified a point mutation in Agrn that results in a partial loss-of-function
      allele, creating a valid model of CMS. The mutation changes phenylalanine 1061 to
      serine in the SEA domain of AGRIN, a poorly characterized motif shared by other
      extracellular proteoglycans. NMJs in homozygous mice progressively degrade
      postnataly. Severity differs with genetic background, in different muscles, and
      in different regions within a muscle in a pattern matching mouse models of motor
      neuron disease. Mutant NMJs have decreased acetylcholine receptor density and an
      increased subsynaptic reticulum, evident by electron microscopy. Synapses
      eventually denervate and the muscles atrophy. Molecularly, several factors
      contribute to the partial loss of AGRIN's function. The mutant protein is found
      at NMJs, but is processed differently than wild-type, with decreased
      glycosylation, changes in sensitivity to the protease neurotrypsin and other
      proteolysis, and less efficient externalization and secretion. Therefore, the
      Agrn point mutation is a model for CMS caused by Agrn mutations and potentially
      other related neuromuscular diseases.

PMID- 21890493
TI  - Common variants of the BRCA1 wild-type allele modify the risk of breast cancer in
      BRCA1 mutation carriers.
AB  - Mutations in the BRCA1 gene substantially increase a woman's lifetime risk of
      breast cancer. However, there is great variation in this increase in risk with
      several genetic and non-genetic modifiers identified. The BRCA1 protein plays a
      central role in DNA repair, a mechanism that is particularly instrumental in
      safeguarding cells against tumorigenesis. We hypothesized that polymorphisms that
      alter the expression and/or function of BRCA1 carried on the wild-type (non
      mutated) copy of the BRCA1 gene would modify the risk of breast cancer in
      carriers of BRCA1 mutations. A total of 9874 BRCA1 mutation carriers were
      available in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) for
      haplotype analyses of BRCA1. Women carrying the rare allele of single nucleotide
      polymorphism rs16942 on the wild-type copy of BRCA1 were at decreased risk of
      breast cancer (hazard ratio 0.86, 95% confidence interval 0.77-0.95, P = 0.003).
      Promoter in vitro assays of the major BRCA1 haplotypes showed that common
      polymorphisms in the regulatory region alter its activity and that this effect
      may be attributed to the differential binding affinity of nuclear proteins. In
      conclusion, variants on the wild-type copy of BRCA1 modify risk of breast cancer
      among carriers of BRCA1 mutations, possibly by altering the efficiency of BRCA1
      transcription.

PMID- 21890500
TI  - Effect of dietary organic and inorganic selenium on antioxidant status, embryo
      development, and reproductive performance in hyperovulatory first-parity gilts.
AB  - This project aimed to determine the effect of Se as inorganic Na-selenite (MSe)
      or organic Se-yeast (OSe) on antioxidant status, hormonal profile, reproductive
      performance, and embryo development in first-parity gilts. Forty-nine gilts were
      allocated to 1 of the 3 dietary treatments starting at first pubertal estrus and
      lasting up to 30 d after AI: control [CONT: basal diet (Se = 0.2 mg/kg) without
      added Se; n = 16], MSe (CONT + 0.3 mg/kg of MSe; n = 16), and OSe (CONT + 0.3
      mg/kg of OSe; n = 17). Blood was collected from all gilts on the day after each
      onset of estrus and on d 30 after AI. Blood was also collected daily from d -4 to
      d +4 of the third onset of estrus (d 0) in 8 CONT, 9 MSe, and 8 OSe cannulated
      gilts. Gilts had received, after d 14 and 15 of their third estrus, a hormonal
      challenge to induce super-ovulation. At slaughter, embryos and corpora lutea (CL)
      were weighed and measured. Blood Se was less (P < 0.01) in CONT than in Se gilts
      and greater in OSe than in MSe (P < 0.01) from the first estrus until d 30 of
      gestation. At the same time, blood Se-dependent glutathione peroxidase (GSH-Px)
      decreased for CONT gilts, whereas it increased for both Se groups. The increase
      was greater in MSe than in OSe gilts (treatment * time, P = 0.02). Plasma 3,3',5
      triiodothyronine and thyroxine concentrations for MSe tended to be less than for
      OSe gilts (P < 0.06). In cannulated gilts, plasma FSH tended to change among
      treatments (treatment * time, P = 0.06), and plasma estradiol-17beta (E(2)) was
      less (P = 0.01) for MSe than for OSe. There was no treatment effect on mean
      litter size or embryonic antioxidant status. The Se content of individual embryos
      was greater for Se-treated than for CONT gilts (P = 0.03), and Se content of
      individual embryos and total litter was greater for OSe than for MSe gilts (P <
      0.01). The length, weight, and protein content of embryos were greater in OSe
      than in MSe gilts (P < 0.05). There was no treatment effect on weight, length, Se
      content, and ferric reducing antioxidant power of CL, but GSH-Px in CL was
      greater for Se than for CONT gilts (P = 0.02). In summary, the Se status response
      of gilts to dietary Se was affected by both the quantity and the source of Se
      dietary supplements. Moreover, the uterine transfer of Se to embryos was improved
      with OSe as compared with MSe, and this was concomitant with an enhanced
      development of embryos.

PMID- 21890501
TI  - Leptin gene haplotypes are associated with change in immunological and
      hematological variables in dairy cow during the peripartum period.
AB  - In this study, the effect of polymorphisms in the leptin gene on the
      hematological variables in periparturient dairy cows was investigated. The
      hematological profile of 67 Holstein cows was assessed for 6 wk around calving.
      The DNA of the cows was genotyped at 6 polymorphic loci within the leptin gene,
      and 7 haplotypes were reconstructed. Significant haplotype substitution effects
      were found, for haplotype 1, on total white blood cell count for 2 wk around
      calving (+0.70 10(3)/MUL, P = 0.05; +1.38 10(3)/MUL, P = 0.0001); on neutrophil
      cell count in the first week after calving (+0.94 10(3)/MUL, P = 0.001); on
      lymphocyte count during the 3 wk before and the first week after calving (+0.32
      10(3)/MUL, P = 0.05; +0.27 10(3)/MUL, P = 0.03; +0.26 10(3)/MUL, P = 0.04; +0.34
      10(3)/MUL, P = 0.01); on red blood cell count during the last week before calving
      and wk 1 and 2 after calving (+0.21 10(6)/MUL, P = 0.02; +0.23 10(6)/MUL, P =
      0.01; +0.20 10(6)/MUL, P = 0.03); on mean corpuscular volume (-1.35 fL, P = 0.01;
      -1.29 fL, P = 0.002; -1.18 fL, P = 0.004; -1.09 fL, P = 0.008; -1.23 fL, P =
      0.003; -1.31 fL, P = 0.003); and on mean corpuscular hemoglobin (-0.37 pg, P =
      0.05; -0.38 pg, P = 0.02; -0.39 pg, P = 0.01; -0.34 pg, P = 0.03; -0.40 pg, P =
      0.01; -0.40 pg, P = 0.01) during all 6 wk analyzed. Significant haplotype
      substitution effects, but opposite those of haplotype-1, were found for haplotype
      2 on white blood cell count (-1.10 10(3)/MUL, P = 0.01; -1.30 10(3)/MUL, P =
      0.002; -1.09 10(3)/MUL, P = 0.01) and neutrophil count (-0.82 10(3)/MUL, P =
      0.02; -0.95 10(3)/MUL, P = 0.005; -0.92 10(3)/MUL, P = 0.01). Haplotype-3
      influenced red blood cell count (-0.23 10(6)/MUL, P = 0.03; -0.28 10(6)/MUL, P =
      0.01; -0.34 10(6)/MUL, P = 0.002) during the last 2 wk before and the first week
      after calving, and also, with effects evident only in wk 3 and 2 before calving,
      mean corpuscular volume (+1.38 fL, P = 0.03; +0.97 fL, P = 0.05; +1.08 fL, P =
      0.05), mean corpuscular hemoglobin (+0.58 pg, P = 0.02; +0.38 pg, P = 0.04; 0.51
      pg, P = 0.01), and red blood cell distribution width (-0.56% P = 0.02; -0.47%, P
      = 0.05). The current study provided evidence that several polymorphisms in the
      leptin gene play a role in the variability of hematological variables during the
      peripartum period, and might be used as genetic markers for improving the
      immunological conditions of dairy cows in critical productive periods.

PMID- 21890502
TI  - Factors affecting storage stability of various commercial phytase sources.
AB  - A 360-d study was performed to evaluate the effects of different environmental
      conditions on storage stability of exogenous phytases. Coated and uncoated
      products from 3 phytase sources [Ronozyme P (DSM Nutritional Products, Basel,
      Switzerland), OptiPhos (Phytex LLC, Sheridan, IN), and Phyzyme (Danisco Animal
      Nutrition, Marlborough, UK)] were stored as pure forms, in a vitamin premix, or
      in a vitamin and trace mineral (VTM) premix. Pure products were stored at -18, 5,
      23, and 37 degrees C (75% humidity). Premixes were stored at 23 and 37 degrees C.
      Sampling was performed on d 0, 30, 60, 90, 120, 180, 270, and 360. Sampling of
      the pure products stored at -18 (lack of sample) and 5 degrees C (because of mold
      growth) was discontinued after d 120. Stability was reported as the residual
      phytase activity (% of initial) at each sampling point. For the stability of the
      pure forms, all interactive and main effects of the phytase product, coating,
      time, and storage temperature were significant (P < 0.01), except for the time *
      coating interaction. When stored at 23 degrees C or less, pure phytases retained
      at least 91, 85, 78, and 71% of their initial phytase activity at 30, 60, 90, and
      120 d of storage, respectively. However, storing pure products at 37 degrees C
      reduced (P < 0.01) phytase stability, with OptiPhos retaining the most (P < 0.01)
      activity. Coating mitigated (P < 0.01) the negative effects of high storage
      temperature for Ronozyme and OptiPhos (from d 90 onward), but not for Phyzyme.
      For the stability of phytase in different forms of storage, all interactive and
      main effects of phytase product, form, coating, time, and temperature of storage
      were significant (P < 0.01). When stored at room temperature (23 degrees C),
      retained phytase activities for most the phytase sources were more than 85, 73,
      and 60% of the initial activity up to 180 d when stored as pure products, vitamin
      premixes, or VTM premixes, respectively. When stored at 37 degrees C, pure
      phytase products had greater (P < 0.01) retention of initial phytase activity
      than when phytases were mixed with the vitamin or VTM premixes. Coated phytases
      stored in any form had greater (P < 0.01) activity retention than the uncoated
      phytases at all sampling periods. Results indicate that storage stability of
      commercially available phytases is affected by duration of storage, temperature,
      product form, coating, and phytase source. Pure products held at 23 degrees C or
      less were the most stable. In premixes, longer storage times and higher
      temperatures reduced phytase activity, but coating mitigated some of these
      negative effects.

PMID- 21890503
TI  - Meat Science and Muscle Biology Symposium: extracellular matrix regulation of
      skeletal muscle formation.
AB  - Skeletal muscle development and growth is a complex process that involves the
      interaction of muscle cells with their extracellular environment. Because muscle
      development involves the interaction of the cell surface and extracellular matrix
      molecules, research focus has been placed on the proteoglycans. Proteoglycans are
      macromolecules containing a central core protein with attached carbohydrates,
      called glycosaminoglycans, that are located at both the cell surface and the
      extracellular matrix. Research focus has been placed on understanding the
      mechanisms of the membrane-associated heparan sulfate proteoglycans, syndecan-4
      and glypican-1, which are both capable of regulating cellular responsiveness to
      fibroblast growth factor 2 (FGF2). Fibroblast growth factor 2 is a potent
      stimulator of muscle cell proliferation and a strong inhibitor of
      differentiation. Studies on syndecan-4 and glypican-1 show that these
      proteoglycans differentially regulate muscle cell proliferation, differentiation,
      and cellular responsiveness to FGF2 with syndecan-4 predominantly modulating
      muscle cell proliferation and glypican-1 modulating differentiation. Site
      directed mutagenesis approaches were used to define the effect of the syndecan-4
      and glypican-1 covalently attached side chains on their activity. In general, a
      functional association was found between the glycosaminoglycan and N-glycosylated
      chains attached to the central core proteins of syndecan-4 and glypican-1
      affecting their regulation of muscle cell proliferation, differentiation, and
      FGF2 responsiveness. Current research efforts are directed at identifying the
      cellular signaling pathways modulated by syndecan-4 and glypican-1.

PMID- 21890504
TI  - Residual intake and body weight gain: a new measure of efficiency in growing
      cattle.
AB  - Interest in improving feed efficiency in cattle is intensifying. Residual feed
      intake (RFI), which is the difference between expected intake and that predicted
      based on energy demands, is now the most commonly used measure of feed efficiency
      over a given time period. However, RFI, as commonly defined, is independent of
      growth rate, which may affect its acceptance by industry. Residual BW gain (RG)
      has also been proposed as a measure of feed efficiency and is represented as the
      residuals from a multiple regression model regressing ADG on both DMI and BW. In
      this study, we propose a new trait, residual intake and BW gain (RIG), which
      retains the favorable characteristic of both RFI and RG being independent of BW,
      but animals superior for RIG have, on average, both greater ADG and reduced DMI.
      Phenotypic and genetic analyses were undertaken on up to 2,605 purebred
      performance-tested bulls. Clear phenotypic differences in DMI and ADG existed
      between animals divergent for RIG. The heritability of RIG was 0.36 +/- 0.06,
      which is consistent with the heritability estimates of RFI and other feed
      efficiency traits measured in the study. The RIG trait was both phenotypically
      and genetically negatively correlated with DMI and positively correlated with
      ADG; no correlation existed between RIG and BW. The advantages of both reduced
      daily DMI and greater ADG in animals superior for RIG are demonstrated compared
      with animals superior for either RFI or RG.

PMID- 21890505
TI  - Meat Science and Muscle Biology Symposium: manipulating meat tenderness by
      increasing the turnover of intramuscular connective tissue.
AB  - Controlled reduction of the connective tissue contribution to cooked meat
      toughness is an objective that would have considerable financial impact in terms
      of added product value. The amount of intramuscular connective tissue in a muscle
      appears connected to its in vivo function, so reduction of the overall connective
      tissue content is not thought to be a viable target. However, manipulation of the
      state of maturity of the collagenous component is a biologically viable target;
      by increasing connective tissue turnover, less mature structures can be produced
      that are functional in vivo but more easily broken down on cooking at
      temperatures above 60 degrees C, thus improving cooked meat tenderness. Recent
      work using cell culture models of fibroblasts derived from muscle and myoblasts
      has identified a range of factors that alter the activity of the principal
      enzymes responsible for connective tissue turnover, the matrix metalloproteinases
      (MMP). Fibroblasts cultured from 3 different skeletal muscles from the same
      animal show different cell proliferation and MMP activity, which may relate to
      the different connective tissue content and architecture in functionally
      different muscles. Expression of MMP by fibroblasts is increased by vitamins that
      can counter the negative effects of oxidative stress on new collagen synthesis.
      Preliminary work using in situ zymography of myotubes in culture also indicates
      increased MMP activity in the presence of epinephrine and reactive oxidative
      species. Comparison of the relative changes in MMP expression from muscle cells
      vs. fibroblasts shows that myoblasts are more responsive to a range of stimuli.
      Muscle cells are likely to produce more of the total MMP in muscle tissue as a
      whole, and the expression of latent forms of the enzymes (i.e., pro-MMP) may vary
      between oxidative and glycolytic muscle fibers within the same muscle. The
      implication is that the different muscle fiber composition of different muscles
      eaten as meat may influence the potential for manipulation of their connective
      tissue turnover.

PMID- 21890506
TI  - Effects of slaughter time post-second injection on carcass cutting yields and
      bacon characteristics of immunologically castrated male pigs.
AB  - Body weights of finishing pigs can be variable within a finishing barn near the
      time of slaughter; therefore, it is common to market pigs over a period of time.
      This allows lighter pigs more time to gain BW and approach a desired end point.
      Use of immunological castration late in life to control boar taint, as an
      alternative to physical castration early in life, increases cutting yields of
      finishing male pigs compared with physical castrates. Because of common marketing
      strategies, it is important for advantages in cutting yields to span a broad
      spectrum of slaughter ages and BW. The primary objectives in this study were to
      evaluate carcass cutting yields, pork quality, belly quality, and bacon
      processing characteristics of immunologically castrated (IC) male pigs fed a
      moderate level of distillers dried grains with solubles and slaughtered at either
      4 wk (early slaughter group) or 6 wk (late slaughter group) post-second
      injection. A total of 156 male pigs (physical castrates or IC males) were
      selected from a population of 1,200 finishing pigs. Data were analyzed with the
      MIXED procedure of SAS as a split-split plot design. Body weights of IC males
      were 3.60 kg heavier (P = 0.03) than physical castrates when slaughtered at 4 wk
      post-second injection and 7.52 kg heavier (P < 0.0001) than physical castrates
      when slaughtered at 6 wk post-second injection. Because of a lack of interaction
      (P > 0.05) between sex and time of slaughter post-second injection, some response
      variables were pooled. Hot carcass weights were not different (P = 0.57) between
      physical castrates (91.98 kg) and IC males (92.52 kg). There was a 2.77
      percentage unit decrease (P < 0.001) in dressing percentage of IC males (71.78%)
      compared with physical castrates (74.55%). Lean cutting yields of IC males were
      2.62 percentage units greater (P < 0.0001) than physical castrates and carcass
      cutting yields were 2.27 percentage units greater (P < 0.0001) for IC males when
      compared with physical castrates. There were no differences between IC males and
      physical castrates for shear force (P = 0.09), ultimate pH (P = 0.57), objective
      color (P >= 0.31), subjective color score (P = 0.64), or drip loss (P = 0.30).
      Bellies from IC males were thinner (P = 0.01) and had narrower belly flops (P <
      0.0001) than bellies from physical castrates. There were no differences (P =
      0.74) in cured belly cooked yield between IC males and physical castrates.
      Overall, immunological castration improved cutting yields, did not affect pork
      quality, made fresh bellies thinner, and did not affect cured belly
      characteristics when pigs were fed a moderate level of distillers dried grains
      with solubles during the finishing phase of production.

PMID- 21890507
TI  - Weaned pig responses to Escherichia coli K88 oral challenge when receiving a
      lysozyme supplement.
AB  - Lysozyme is a low-molecular-weight protein with antimicrobial properties. An
      experiment was conducted to investigate the response of piglets receiving a water
      soluble lysozyme supplement [Entegard (EG), Neova Technologies Inc., Abbotsford,
      British Columbia, Canada; 4,000 lysozyme units/mg] after oral challenge with
      enterotoxigenic Escherichia coli (ETEC). A total of 36 individually housed
      weanling pigs were randomly allotted to 1 of the 4 treatments, with 9 replicates
      per treatment. Treatments were a control (CONT, no additive), antibiotic (AB; 2.5
      g/kg of feed of antibiotic with chlortetracycline, sulfamethazine, and
      penicillin), and EG delivered in the drinking water at concentrations of 0.1%
      (EG1) and 0.2% (EG2). All pigs received a basal diet similar in composition and
      nutrients, except for pigs receiving the AB diet, which had an added antibiotic.
      Pigs were acclimated to treatments for a 7-d period to monitor growth
      performance. On d 8, blood samples were collected from each pig to obtain serum,
      and each pig was gavaged with 6 mL (2 * 10(9) cfu/mL) of ETEC solution. Pigs were
      monitored for another 7 d to assess incidences of diarrhea and growth
      performance, and then all pigs were killed to obtain intestinal tissue and
      digesta samples. Treatments did not influence growth performance throughout the
      study. Greater ETEC counts were observed in the ileal mucosal scrapings (P =
      0.001) and colonic digesta (P = 0.025) of pigs in the CONT group compared with
      pigs in the AB and EG1 groups. Pigs receiving AB and EG1 had greater (P < 0.05)
      small intestinal weights and ileal villus heights than pigs receiving CONT;
      however, the ileal villus height-to-crypt depth ratio was greater in pigs fed the
      AB diet (1.69) compared with those fed the CONT diet (1.34), whereas pigs
      receiving EG1 were intermediate. Pigs in the EG1 group showed greater (P < 0.001)
      serum tumor necrosis factor alpha and IL-6 concentrations before ETEC challenge;
      however, at 7 d postchallenge, pigs receiving EG2 showed the least (P < 0.05)
      circulating tumor necrosis factor alpha and IL-6 concentrations. Overall, better
      intestinal growth and development, as well as decreased ETEC counts on the
      intestinal mucosa and serum proinflammatory cytokines, suggest that EG can
      maintain gut health and function in piglets commensurate with antibiotics.
      However, it is noteworthy that at the largest dose tested, EG seemed to have a
      dramatic effect on proinflammatory cytokines but had a minimal or no effect on
      the other response criteria.

PMID- 21890508
TI  - Therapeutic potential of pegylated hemin for reactive oxygen species-related
      diseases via induction of heme oxygenase-1: results from a rat hepatic
      ischemia/reperfusion injury model.
AB  - Many diseases and pathological conditions, including ischemia/reperfusion (I/R)
      injury, are the consequence of the actions of reactive oxygen species (ROS).
      Controlling ROS generation or its level may thus hold promise as a standard
      therapeutic modality for ROS-related diseases. Here, we assessed heme oxygenase-1
      (HO-1), which is a crucial antioxidative, antiapoptotic molecule against
      intracellular stresses, for its therapeutic potential via its inducer, hemin. To
      improve the solubility and in vivo pharmacokinetics of hemin for clinical
      applications, we developed a micellar hemin by conjugating it with poly(ethylene
      glycol) (PEG) (PEG-hemin). PEG-hemin showed higher solubility in water and
      significantly prolonged plasma half-life than free hemin, which resulted from its
      micellar nature with molecular mass of 126 kDa in aqueous media. In a rat I/R
      model, administration of PEG-hemin significantly elevated HO-1 expression and
      enzymatic activity. This induction of HO-1 led to significantly improved liver
      function, reduced apoptosis and thiobarbituric acid reactive substances of the
      liver, and decreased inflammatory cytokine production. PEG-hemin administration
      also markedly improved hepatic blood flow. These results suggest that PEG-hemin
      exerted a significant cytoprotective effect against I/R injury in rat liver by
      inducing HO-1 and thus seems to be a potential therapeutic for ROS-related
      diseases, including I/R injury.

PMID- 21890509
TI  - Transient lower esophageal sphincter relaxation pharmacokinetic-pharmacodynamic
      modeling: count model and repeated time-to-event model.
AB  - Transient lower esophageal sphincter relaxation (TLESR) is the major mechanism
      for gastroesophageal reflux. Characterizations of candidate compounds for
      reduction of TLESRs are traditionally done through summary exposure and response
      measures and would benefit from model-based analyses of exposure-TLESR events
      relationships. Pharmacokinetic (PK)-pharmacodynamic (PD) modeling approaches
      treating TLESRs either as count data or repeated time-to-event (RTTE) data were
      developed and compared in terms of their ability to characterize system and drug
      characteristics. Vehicle data comprising 294 TLESR events were collected from
      nine dogs. Compound [(R)-(+)-[2,3-dihydro-5-methyl-3-(4
      morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone
      mesylate (WIN55212-2)] data containing 66 TLESR events, as well as plasma
      concentrations, were obtained from four dogs. Each experiment lasted for 45 min
      and was initiated with a meal. Counts in equispaced 5- and 1-min intervals were
      modeled based on a Poisson probability distribution model. TLESR events were
      analyzed with the RTTE model. The PK was connected to the PD with a one
      compartment model. Vehicle data were described by a baseline and a surge
      function; the surge peak was determined to be approximately 9.69 min by all
      approaches, and its width in time at half-maximal intensity was 5 min (1-min
      count and RTTE) or 10 min (5-min count). TLESR inhibition by WIN55212-2 was
      described by an I(max) model, with an IC(50) of on average 2.39 nmol . l(-1).
      Modeling approaches using count or RTTE data linked to a dynamic PK-PD
      representation of exposure are superior to using summary PK and PD measures and
      are associated with a higher power for detecting a statistically significant drug
      effect.

PMID- 21890510
TI  - Chronic hypoxia-induced acid-sensitive ion channel expression in chemoafferent
      neurons contributes to chemoreceptor hypersensitivity.
AB  - Previously we demonstrated that chronic hypoxia (CH) induces an inflammatory
      condition characterized by immune cell invasion and increased expression of
      inflammatory cytokines in rat carotid body. It is well established that chronic
      inflammatory pain induces the expression of acid-sensitive ion channels (ASIC) in
      primary sensory neurons, where they contribute to hyperalgesia and allodynia. The
      present study examines the effect of CH on ASIC expression in petrosal ganglion
      (PG), which contains chemoafferent neurons that innervate oxygen-sensitive type I
      cells in the carotid body. Five isoforms of ASIC transcript were increased ~1.5
      2.5-fold in PG following exposure of rats to 1, 3, or 7 days of hypobaric hypoxia
      (380 Torr). ASIC transcript was not increased in the sympathetic superior
      cervical ganglion (SCG). In the PG, CH also increased the expression of channel
      interacting PDZ domain protein, a scaffolding protein known to enhance the
      surface expression and the low pH-induced current density mediated by ASIC3.
      Western immunoblot analysis showed that CH elevated ASIC3 protein in PG, but not
      in SCG or the (sensory) nodose ganglion. ASIC3 transcript was likewise elevated
      in PG neurons cultured in the presence of inflammatory cytokines. Increased ASIC
      expression was blocked in CH rats concurrently treated with the nonsteroidal anti
      inflammatory drug ibuprofen (4 mg.kg(-1).day(-1)). Electrophysiological recording
      of carotid sinus nerve (CSN) activity in vitro showed that the specific ASIC
      antagonist A-317567 (100 MUM) did not significantly alter hypoxia-evoked activity
      in normal preparations but blocked ~50% of the hypoxic response following CH.
      Likewise, a high concentration of ibuprofen, which is known to block ASIC1a,
      reduced hypoxia-evoked CSN activity by ~50% in CH preparations. Our findings
      indicate that CH induces inflammation-dependent phenotypic adjustments in
      chemoafferent neurons. Following CH, ASIC are important participants in
      chemotransmission between type I cells and chemoafferent nerve terminals, and
      these proton-gated channels appear to enhance chemoreceptor sensitivity.

PMID- 21890511
TI  - Injury and repair in the very immature lung following brief mechanical
      ventilation.
AB  - Mechanical ventilation (MV) of very premature infants contributes to lung injury
      and bronchopulmonary dysplasia (BPD), the effects of which can be long-lasting.
      Little is currently known about the ability of the very immature lung to recover
      from ventilator-induced lung injury. Our objective was to determine the ability
      of the injured very immature lung to repair in the absence of continued
      ventilation and to identify potential mechanisms. At 125 days gestational age
      (days GA, 0.85 of term), fetal sheep were partially exposed by hysterotomy under
      anesthesia and aseptic conditions; they were intubated and ventilated for 2 h
      with an injurious MV protocol and then returned to the uterus to continue
      development. Necropsy was performed at either 1 day (short-term group, 126 days
      GA, n = 6) or 15 days (long-term group, 140 days GA, n = 5) after MV; controls
      were unventilated (n = 7-8). At 1 day after MV, lungs displayed signs of injury,
      including hemorrhage, disorganized elastin and collagen deposition in the distal
      airspaces, altered morphology, significantly reduced secondary septal crest
      density, and decreased airspace. Bronchioles had thickened epithelium with
      evidence of injury and sloughing. Relative mRNA levels of early response genes
      (connective tissue growth factor, cysteine-rich 61, and early growth response-1)
      and proinflammatory cytokines [interleukins (IL)-1beta, IL-6, IL-8, tumor
      necrosis factor-alpha, and transforming growth factor-beta] were not different
      between groups 1 day after MV. At 15 days after MV, lung structure was normal
      with no evidence of injury. We conclude that 2 h of MV induces severe injury in
      the very immature lung and that these lungs have the capacity to repair
      spontaneously in the absence of further ventilation.

PMID- 21890512
TI  - Mitochondrial DNA integrity may be a determinant of endothelial barrier
      properties in oxidant-challenged rat lungs.
AB  - In cultured pulmonary artery endothelial cells and other cell types,
      overexpression of mt-targeted DNA repair enzymes protects against oxidant-induced
      mitochondrial DNA (mtDNA) damage and cell death. Whether mtDNA integrity governs
      functional properties of the endothelium in the intact pulmonary circulation is
      unknown. Accordingly, the present study used isolated, buffer-perfused rat lungs
      to determine whether fusion proteins targeting 8-oxoguanine DNA glycosylase 1
      (Ogg1) or endonuclease III (Endo III) to mitochondria attenuated mtDNA damage and
      vascular barrier dysfunction evoked by glucose oxidase (GOX)-generated hydrogen
      peroxide. We found that both Endo III and Ogg1 fusion proteins accumulated in
      lung cell mitochondria within 30 min of addition to the perfusion medium. Both
      constructs prevented GOX-induced increases in the vascular filtration
      coefficient. Although GOX-induced nuclear DNA damage could not be detected,
      quantitative Southern blot analysis revealed substantial GOX-induced oxidative
      mtDNA damage that was prevented by pretreatment with both fusion proteins. The
      Ogg1 construct also reversed preexisting GOX-induced vascular barrier dysfunction
      and oxidative mtDNA damage. Collectively, these findings support the ideas that
      mtDNA is a sentinel molecule governing lung vascular barrier responses to oxidant
      stress in the intact lung and that the mtDNA repair pathway could be a target for
      pharmacological intervention in oxidant lung injury.

PMID- 21890513
TI  - S-carboxymethylcysteine inhibits adherence of Streptococcus pneumoniae to human
      alveolar epithelial cells.
AB  - Streptococcus pneumoniae is a major pathogen of respiratory infections that
      utilizes platelet-activating factor receptor (PAFR) for firm adherence to host
      cells. The mucolytic agent S-carboxymethylcysteine (S-CMC) has been shown to
      exert inhibitory effects against infection by several respiratory pathogens
      including S. pneumoniae in vitro and in vivo. Moreover, clinical studies have
      implicated the benefits of S-CMC in preventing exacerbation of chronic
      obstructive pulmonary disease, which is considered to be related to respiratory
      infections. In this study, to assess whether the potency of S-CMC is attributable
      to inhibition of pneumococcal adherence to host cells, an alveolar epithelial
      cell line stimulated with interleukin-1alpha was used as a model of inflamed
      epithelial cells. Despite upregulation of PAFR by inflammatory activation,
      treatment with S-CMC efficiently inhibited pneumococcal adherence to host
      epithelial cells. In order to gain insight into the inhibitory mechanism, the
      effects of S-CMC on PAFR expression were also investigated. Following treatment
      with S-CMC, PAFR expression was reduced at both mRNA and post-transcriptional
      levels. Interestingly, S-CMC was also effective in inhibiting pneumococcal
      adherence to cells transfected with PAFR small interfering RNAs. These results
      indicate S-CMC as a probable inhibitor targeting numerous epithelial receptors
      that interact with S. pneumoniae.

PMID- 21890514
TI  - Environmental pH changes, but not the LuxS signalling pathway, regulate SpeB
      expression in M1 group A streptococci.
AB  - The autoinducer-2/LuxS signalling pathway participates in quorum sensing in
      diverse bacterial species. In group A streptococci (GAS), LuxS has been shown to
      be involved in regulating the expression of several important virulence factors.
      Streptococcal pyrogenic exotoxin B (SpeB), a cysteine protease that has important
      roles in GAS pathogenesis, is positively regulated by LuxS in M3 and M5 strains.
      In the present study, it was found that the supernatant harvested from an
      overnight culture stimulated M1 strains to express speB. However, mutation of the
      luxS gene in M1 strains or treating M1 strains with luxS mutant culture
      supernatant did not affect speB expression, indicating that the LuxS pathway is
      not involved in regulation of speB expression in M1 strains. In addition, the
      acid property of culture broth was found to be able to stimulate M1 strains to
      express speB in the same LuxS-independent manner. These results indicate that
      speB expression in M1 strains is induced by environmental pH changes but is not
      regulated by the LuxS signalling pathway.

PMID- 21890515
TI  - Tellurite-reduction-based assay for screening potential antibiotics.

PMID- 21890516
TI  - Nuclear factor kappaB is a key transcription factor in the duodenal contractility
      alterations induced by lipopolysaccharide.
AB  - Alterations in intestinal motility are one of the features of sepsis induced by
      lipopolysaccharide (LPS). This study investigated the role of the nuclear
      transcription factor kappaB (NF-kappaB) in the LPS-induced duodenal contractility
      alterations, generation of reactive oxygen species (ROS) and production of
      cytokines in rabbit duodenum. Rabbits were treated with saline, LPS,
      sulfasalazine + LPS, pyrrolidinedithiocarbamate (PDTC) + LPS or RO 106-9920 +
      LPS. Contractility studies were performed in an organ bath. The formation of
      products of oxidative damage to proteins (carbonyls) and lipids (malondialdehyde
      and 4-hydroxyalkenals) was quantified in intestinal tissue and plasma. The
      protein expression of NF-kappaB was measured by Western blot. The DNA binding
      activity of NF-kappaB was evaluated by transcription factor activity assay. The
      expression of interleukin-1beta, tumour necrosis factor alpha (TNF-alpha),
      interleukin-6, interleukin-10 and interleukin-8 mRNA was determined by RT-PCR.
      Sulfasalazine, PDTC and RO 106-9920 blocked the inhibitory effect of LPS on
      contractions induced by ACh in the longitudinal smooth muscle of rabbit duodenum.
      Sulfasalazine, PDTC and RO 106-9920 reduced the increased levels of
      malondialdehyde and 4-hydroxyalkenals and the carbonyls induced by LPS in plasma.
      Lipopolysaccharide induced the activation, translocation to the nucleus and DNA
      binding of NF-kappaB. Lipopolysaccharide increased the mRNA expression of
      interleukin-6 and TNF-alpha in duodenal tissue, and this effect was partly
      reversed by PDTC, sulfasalazine and RO 106-9920. In conclusion, NF-kappaB
      mediates duodenal contractility disturbances, the generation of ROS and the
      increase in the expression of interleukin-6 and TNF-alpha induced by LPS.
      Sulfasalazine, PDTC and RO 106-9920 may be therapeutic drugs to reduce these
      effects.

PMID- 21890517
TI  - Effects of chronic caffeine intake and low-intensity exercise on skeletal muscle
      of Wistar rats.
AB  - Caffeine can affect muscle cell physiology and the inflammatory response during
      exercise. The purpose of this study was to analyse muscle damage markers and
      inflammatory cell infiltration into the soleus muscle of sedentary and exercised
      animals submitted to chronic caffeine intake. Thirty-two male Wistar rats were
      divided into the following four groups (n = 8 per group): sedentary control
      (SCO); sedentary + caffeine (SCAF); trained control (TCO); and trained + caffeine
      (TCAF). The animals were housed in individual cages and received tap water or
      caffeine (1 mg ml(-1)); they were maintained at rest or submitted to swimming for
      up to 40 min day(-1) with a 4% load, five times per week for 30 days. Blood
      samples were collected for analysis of serum lactate, creatine kinase and
      calcium. The right soleus muscle and the epididymal fat depot were weighed, and
      the muscle was submitted to histological analysis. Training and caffeine did not
      change body or muscle weight, food and liquid intake or serum calcium levels
      among groups. Decreased fat tissue (P < 0.05) was observed in the SCAF (4.05 +/-
      1.03 g), TCO (4.14 +/- 0.78 g) and TCAF groups (4.02 +/- 1.02 g) compared with
      the SCO group (5.31 +/- 1.06 g). Serum creatine kinase activity was significantly
      reduced in the SCAF (787.3 +/- 230.3 U l(-1)), TCO (775.3 +/- 232.3 U l(-1)) and
      TCAF groups (379.5 +/- 110.5 U l(-1)) compared with the SCO group (1610.2 +/-
      276.5 U l(-1)). Few damaged muscle fibres (P < 0.05) were found in SCAF (16.7 +/-
      12.8%) and TCAF groups (17.3 +/- 11.7%) compared with the SCO group (53.6 +/-
      13.9%). The SCAF group presented fewer fields with inflammatory cells (7.6 +/-
      8.7 fields) compared with the SCO group (123 +/- 146 fields). The results suggest
      that the chronic intake of caffeine, as well as chronic low-intensity exercise,
      decreased muscle damage and inflammatory infiltration into skeletal muscle.

PMID- 21890518
TI  - Modulation of nitric oxide affects myocardial perfusion-contraction matching in
      anaesthetized dogs with recurrent no-flow ischaemia.
AB  - Myocardial perfusion and contraction are closely coupled; however, the effect of
      recurrent no-flow ischaemia on perfusion-contraction matching remains to be
      established. In the present studies, we examined the influence of modulating
      nitric oxide availability on perfusion-contraction matching after recurrent no
      flow ischaemia in acute open-chest, anaesthetized dogs. The following three
      groups were studied: (1) saline; (2) L-NAME (10 mg kg(-1) I.V.); and (3)
      enalaprilat (1.5 mg kg(-1) I.V.). Regional myocardial blood flow was measured
      with microspheres and contractile function with piezoelectric crystals to
      determine systolic wall thickening. Dogs underwent four cycles of 5 min acute
      ischaemia and 5 min coronary reperfusion; area at risk was similar for all
      groups. In all dogs, ischaemic zone contractile function was depressed after
      recurrent no-flow ischaemia despite increased myocardial blood flow during
      reperfusion; contractile function was further depressed during L-NAME and was
      partly restored with enalaprilat. Within the ischaemic region, blood flow in
      subendocardial and subepicardial layers increased significantly compared with
      baseline during each reperfusion period independently of treatment. Our findings
      suggest that reduced NO availability can significantly impair myocardial
      perfusion-contraction matching, which is partly restored by administration of an
      NO donor.

PMID- 21890519
TI  - Sensory and sympathetic nerve contributions to the cutaneous vasodilator response
      from a noxious heat stimulus.
AB  - We investigated the roles of sensory and noradrenergic sympathetic nerves on the
      cutaneous vasodilator response to a localized noxious heating stimulus. In two
      separate studies, four forearm skin sites were instrumented with microdialysis
      fibres, local heaters and laser-Doppler probes. Skin sites were locally heated
      from 33 to 42  degrees C or rapidly to 44  degrees C (noxious). In the first
      study, we tested sensory nerve involvement using EMLA cream. Treatments were as
      follows: (1) control 42  degrees C; (2) EMLA 42  degrees C; (3) control 44
      degrees C; and (4) EMLA 44  degrees C. At the EMLA-treated sites, the axon reflex
      was reduced compared with the control sites during heating to 42  degrees C (P <
      0.05). There were no differences during the plateau phase (P > 0.05). At both the
      sites heated to 44  degrees C, the initial peak and nadir became
      indistinguishable, and the EMLA-treated sites were lower compared with the
      control sites during the plateau phase (P < 0.05). In the second study, we tested
      the involvement of noradrenergic sympathetic nerves in response to the noxious
      heating using bretylium tosylate (BT). Treatments were as follows: (1) control 42
      degrees C; (2) BT 42  degrees C; (3) control 44  degrees C; and (4) BT 44 
      degrees C. Treatment with BT at the 42  degrees C sites resulted in a marked
      reduction in both the axon reflex and the secondary plateau (P < 0.05). At the 44
      degrees C sites, there was no apparent initial peak or nadir, but the plateau
      phase was reduced at the BT-treated sites (P < 0.05). These data suggest that
      both sympathetic nerves and sensory nerves are involved during the vasodilator
      response to a noxious heat stimulus.

PMID- 21890521
TI  - Neural control of the circulation during exercise: insights from the 1970-1971
      Oxford studies.
AB  - During exercise the magnitude of the cardiovascular response is closely matched
      to the intensity of the exercise. In achieving this appropriate matching, an
      important role is played by the autonomic nervous system. Two mechanisms have
      been postulated to regulate this response. In one mechanism the changes in
      autonomic nerve activity to the heart and blood vessels are caused by signals
      arising in a central area of the brain and in the other mechanism the changes are
      caused by signals arising in the contracting skeletal muscle. In 1970-71 two
      studies were performed in Oxford which furthered our understanding of these two
      mechanisms. In one of these studies it was shown in cats that a reflex arising in
      the contracting skeletal muscle reflexly increased blood pressure and heart rate
      and that the thinly myelinated (Group III or A ) and the unmyelinated (Group IV
      or C) afferent nerve fibers were responsible. In the second of these studies it
      was shown in humans that a central mechanism could also increase the blood
      pressure and heart rate during static contraction at a fixed force. Tendon
      vibration of a skeletal muscle induces an involuntary reflex contraction.
      Utilizing this effect the central command needed to produce the same tension
      development was reduced or increased. When the same force was achieved with less
      central command the cardiovascular response was reduced and with more central
      command was increased. This demonstrated that descending motor commands from
      higher brain centers have an effect on the cardiovascular response to exercise.

PMID- 21890520
TI  - Low-frequency power of heart rate variability is not a measure of cardiac
      sympathetic tone but may be a measure of modulation of cardiac autonomic outflows
      by baroreflexes.
AB  - Power spectral analysis of heart rate variability has often been used to assess
      cardiac autonomic function; however, the relationship of low-frequency (LF) power
      of heart rate variability to cardiac sympathetic tone has been unclear. With or
      without adjustment for high-frequency (HF) power, total power or respiration, LF
      power seems to provide an index not of cardiac sympathetic tone but of baroreflex
      function. Manipulations and drugs that change LF power or LF:HF may do so not by
      affecting cardiac autonomic outflows directly but by affecting modulation of
      those outflows by baroreflexes.

PMID- 21890522
TI  - Endogenous hydrogen peroxide in paraventricular nucleus mediates sympathetic
      activation and enhanced cardiac sympathetic afferent reflex in renovascular
      hypertensive rats.
AB  - An enhancement of the cardiac sympathetic afferent reflex (CSAR) contributes to
      sympathetic activation in renovascular hypertension. Angiotensin II in the
      paraventricular nucleus (PVN) augments the CSAR and increases sympathetic outflow
      and blood pressure. The present study aimed to determine whether endogenous
      hydrogen peroxide in the PVN mediated the enhanced CSAR, sympathetic activity and
      the effects of angiotensin II in the PVN in renovascular hypertension induced by
      the two-kidney, one-clip method (2K1C) in rats. At the end of the fourth week,
      the rats underwent sino-aortic and vagal denervation under general anaesthesia
      with urethane and alpha-chloralose. Renal sympathetic nerve activity (RSNA) and
      mean arterial pressure (MAP) were recorded. The CSAR was evaluated by the RSNA
      response to epicardial application of bradykinin. Microinjection of polyethylene
      glycol-catalase (PEG-CAT), an analogue of endogenous catalase, into the PVN
      decreased the RSNA and MAP and abolished the CSAR in both sham-operated and 2K1C
      rats. Microinjection into the PVN of the catalase inhibitor, aminotriazole,
      increased the RSNA and MAP and enhanced the CSAR. The effects of PEG-CAT or
      aminotriazole were greater in 2K1C rats than in sham-operated animals. The
      effects of angiotensin II in the PVN were abolished by pretreatment with PEG-CAT
      in both sham-operated and 2K1C rats; however, aminotriazole failed to potentiate
      the effects of angiotensin II. The catalase activity was decreased but the
      H(2)O(2) levels were increased in the PVN of 2K1C rats. These results indicate
      that endogenous H(2)O(2) in the PVN not only mediates the enhanced sympathetic
      activity and CSAR, but also the effects of angiotensin II in the PVN in
      renovascular hypertensive rats.

PMID- 21890523
TI  - Anoctamin 2/TMEM16B: a calcium-activated chloride channel in olfactory
      transduction.
AB  - In vertebrate olfactory transduction, a Ca(2+)-dependent Cl(-) efflux greatly
      amplifies the odorant response. The binding of odorants to receptors in the cilia
      of olfactory sensory neurons activates a transduction cascade that involves the
      opening of cyclic nucleotide-gated channels and the entry of Ca(2+) into the
      cilia. The Ca(2+) activates a Cl(-) current that, in the presence of a maintained
      elevated intracellular Cl(-) concentration, produces an efflux of Cl(-) ions and
      amplifies the depolarization. In this review, we summarize evidence supporting
      the hypothesis that anoctamin 2/TMEM16B is the main, or perhaps the only,
      constituent of the Ca(2+)-activated Cl(-) channels involved in olfactory
      transduction. Indeed, studies from several laboratories have shown that anoctamin
      2/TMEM16B is expressed in the ciliary layer of the olfactory epithelium, that
      there are remarkable functional similarities between currents in olfactory
      sensory neurons and in HEK 293 cells transfected with anoctamin 2/TMEM16B, and
      that knockout mice for anoctamin 2/TMEM16B did not show any detectable Ca(2+)
      activated Cl(-) current. Finally, we discuss the involvement of Ca(2+)-activated
      Cl(-) channels in the transduction process of vomeronasal sensory neurons and the
      physiological role of these channels in olfaction.

PMID- 21890524
TI  - Effect of physical restraint on the limits of thermoregulation in telemetered
      rats.
AB  - Physical restraint of rodents is needed for nose-only exposure to airborne
      toxicants and is also used as a means of psychological stress. Hyperthermia is
      often observed in restrained rats, presumably as a result of impairments in heat
      dissipation. However, such a hyperthermic response should be dependent on the
      prevailing ambient conditions. To understand how ambient temperature (T(a))
      affects the thermoregulatory response to restraint, core temperature (T(c)) and
      heart rate (HR) were monitored by telemetry in rats subjected to 1 h of physical
      restraint while T(a) was maintained at 14-30  degrees C in 2  degrees C
      increments. The T(c) of unrestrained rats was unaffected by T(a). During
      restraint, T(c) was elevated at ambient temperatures with the exception of 14 
      degrees C, at which the rats became mildly hypothermic. There was an inverse
      relationship between T(a) and HR in both unrestrained and restrained rats;
      however, HR was significantly elevated in restrained rats at all ambient
      temperatures except 22 and 24  degrees C. Heat loss from the tail, estimated from
      T(c) and tail skin temperature, was markedly reduced at all but the highest
      ambient temperatures in restrained rats. The data suggest that the T(a) limits of
      normothermia are narrowed in the restrained rat. That is, between 16 and 20 
      degrees C, the rat maintains a relatively stable T(c) that is slightly elevated
      above that of the unrestrained rat. At ambient temperatures above or below this
      range, the rat shows signs of hyperthermia and hypothermia, respectively. In
      contrast, the limits of normothermia for unrestrained rats range from 14 (or
      lower) to 30  degrees C. Overall, the ideal T(a) for restrained rats appears to
      be 20  degrees C and no higher than 22  degrees C for the thermoregulatory system
      to maintain a regulated T(c) in rats well adapted to physical restraint.

PMID- 21890525
TI  - Relevance of the volume-axis intercept, V0, compared with the slope of end
      systolic pressure-volume relationship in response to large variations in inotropy
      and afterload in rats.
AB  - The end-systolic pressure-volume relationship (ESPVR) is proposed and used as a
      reliable index of left ventricular (LV) contractility despite the fact that its
      afterload independence has been challenged. Furthermore, the physiological
      relevance of its volume-axis intercept, V(0), remains unclear. Systemic
      haemodynamics and pressure-volume loops obtained by inferior vena cava occlusion
      were recorded in 21 rats anaesthetized by isoflurane inhalation and instrumented
      with a conductance pressure-volume catheter in response to incremental I.V. doses
      of adrenaline, dobutamine, phenylephrine, metoprolol, papaverine and isoflurane
      inhalation. In conditions with large variations (+/- 100%) of both inotropy and
      afterload, infusion of negative inotropic drugs was associated with a dose
      dependent rightward shift of ESPVR accompanied by a decrease in its slope (end
      systolic elastance, E(es)), whereas positive inotropic agents produced an
      isolated decrease in V(0). With the predominant vasoactive drugs, there was a
      dose-dependent change in E(es) without major horizontal shifts, demonstrating
      that this slope mainly represents LV afterload rather than inotropy. When
      contractility was altered, V(0) was negatively correlated to the preload-adjusted
      contractility index, PAdP/dt(max), demonstrating that a reduced V(0) provides a
      good reflection of increased LV contractility. From these results, we computed a
      logarithmically adjusted E(es)/V(0) ratio, which resulted in reasonably strong
      concordance with PAdP/dt(max), including all the investigated drugs and dosages
      [n = 288; bias, 0.8 +/- 16.2% (SD)]. Concordance with E(es) (bias, 7.2 +/- 58.7%)
      or V(0) (bias, -0.6 +/- 33.4%), used alone or with other commonly used
      contractility indices, was far less significant. In contrast to E(es), V(0)
      provides a relatively good LV contractility index because it is much less
      sensitive to afterload.

PMID- 21890526
TI  - Exercise as migraine prophylaxis: a randomized study using relaxation and
      topiramate as controls.
AB  - AIM: Scientific evidence regarding exercise in migraine prophylaxis is required.
      Therefore this study aimed to evaluate the effects of exercise in migraine
      prevention. METHODS: In a randomized, controlled trial of adults with migraine,
      exercising for 40 minutes three times a week was compared to relaxation according
      to a recorded programme or daily topiramate use, which was slowly increased to
      the individual's highest tolerable dose (maximum 200 mg/day). The treatment
      period lasted for 3 months, and migraine status, quality of life, level of
      physical activity, and oxygen uptake were evaluated. The primary efficacy
      variable was the mean reduction of the frequency of migraine attacks during the
      final month of treatment compared with the baseline. RESULTS: Ninety-one patients
      were randomized and included in the intention-to-treat analysis. The primary
      efficacy variable showed a mean reduction of 0.93 (95% confidence interval (CI)
      0.31-1.54) attacks in the exercise group, 0.83 (95% CI 0.22-1.45) attacks in the
      relaxation group, and 0.97 (95% CI 0.36-1.58) attacks in the topiramate group. No
      significant difference was observed between the groups (p = 0.95). CONCLUSION:
      Exercise may be an option for the prophylactic treatment of migraine in patients
      who do not benefit from or do not want to take daily medication.

PMID- 21890527
TI  - Individual monitoring for external radiation at accelerator facilities.
AB  - Individual monitoring at accelerator facilities is discussed, within the
      framework set out by the International Commission on Radiological Protection and
      with reference to the implementation of the recommendations of that body within
      the European Basic Safety Standards. Legislation in other parts of the world may
      differ, but a worldwide perspective on this subject would be too exhaustive. The
      fields at accelerator facilities are contrasted in terms of particle type and
      energy with those encountered at more conventional sites within the nuclear fuel
      cycle, medical applications and general industry. The implications for individual
      monitoring are discussed in relation to the dose quantities for these accelerator
      fields and also with respect to the personal dosemeters options.

PMID- 21890528
TI  - Review of bubble detector response characteristics and results from space.
AB  - A passive neutron-bubble dosemeter (BD), developed by Bubble Technology
      Industries, has been used for space applications. Both the bubble detector
      personal neutron dosemeter and bubble detector spectrometer have been studied at
      ground-based facilities in order to characterise their response due to neutrons,
      heavy ion particles and protons. This technology was first used during the
      Canadian-Russian collaboration aboard the Russian satellite BION-9, and
      subsequently on other space missions, including later BION satellites, the space
      transportation system, Russian MIR space station and International Space Station.
      This paper provides an overview of the experiments that have been performed for
      both ground-based and space studies in an effort to characterise the response of
      these detectors to various particle types in low earth orbit and presents results
      from the various space investigations.

PMID- 21890530
TI  - Intimate partner violence against women in the capital province of Sri Lanka:
      prevalence, risk factors, and help seeking.
AB  - This article presents findings from a cross-sectional community survey exploring
      intimate partner violence (IPV) against women in the Western province of Sri
      Lanka. Findings show that lifetime prevalence of physical violence (34%),
      controlling behavior (30%), and emotional abuse (19%) was high and the prevalence
      of sexual violence was low (5%). Young women and those with partners who abused
      alcohol/drugs and had extra-marital affairs are at increased risk of violence.
      Although living in a patriarchal society, low prevalence of child marriages and
      lack of dowry-related violence could be to Sri Lankan women's advantage relative
      to their Asian counterparts in preventing IPV.

PMID- 21890529
TI  - Radioactivity of 210Pb in Japanese cigarettes and radiation dose from smoking
      inhalation.
AB  - It is well known that cigarette tobaccos contain naturally occurring radioactive
      nuclides such as (210)Pb and (210)Po. In many countries, the radioactivity of
      tobaccos has been measured to estimate the effective dose from smoking
      inhalation. The present study covered 24 cigarette brands including the top 20 of
      sales in Japan between April 2008 and March 2009. The activity concentrations of
      (210)Pb were measured by gamma-ray spectrometry, and then those of its progeny
      ((210)Po) were evaluated assuming the radioactive equilibrium between the two
      nuclides. Their concentrations were in the range of 2-14 mBq cigarette(-1) with
      an arithmetic mean of 8+/-3 mBq cigarette(-1). The annual committed effective
      doses were also calculated, based on the scenario that a smoker consumes 20
      cigarettes a day. The average doses from (210)Pb and (210)Po inhalations were
      22+/-9 and 68+/-27 MUSv y(-1), respectively.

PMID- 21890531
TI  - A Canadian model for building university and community partnerships: centre for
      research & education on violence against women and children.
AB  - The importance of Canadian research on violence against women became a national
      focus after the 1989 murder of 14 women at Ecole Polytechnique in Montreal. This
      tragedy led to several federal government studies that identified a need to
      develop centers for applied research and community-university alliances on
      violence against women. One such center is the Centre for Research & Education on
      Violence against Women and Children. The Centre was founded in London, Canada in
      1992 out of a partnership of a university, a community college, and community
      services. The centre's history and current activities are summarized as a model
      for the development and sustainability of similar centers.

PMID- 21890532
TI  - Upregulation of aldolase B and overproduction of methylglyoxal in vascular
      tissues from rats with metabolic syndrome.
AB  - AIMS: Methylglyoxal (MG) overproduction has been reported in metabolic syndrome
      with hyperglycaemia (diabetes) or without hyperglycaemia (hypertension), and the
      underlying mechanism was investigated. METHODS AND RESULTS: Contributions of
      different pathways or enzymes to MG formation were evaluated in aorta or cultured
      vascular smooth muscle cells (VSMCs). In all four animal models of metabolic
      syndrome, i.e. chronically fructose-fed hypertensive Sprague-Dawley rats,
      spontaneously hypertensive rats, obese non-diabetic Zucker rats, and diabetic
      Zucker rats, serum and aortic MG and fructose levels were increased, and the
      expression of GLUT5 (transporting fructose) and aldolase B (converting fructose
      to MG) in aorta were up-regulated. Aortic expressions of aldolase A,
      semicarbazide-sensitive amine oxidase (SSAO), and cytochrome P450 2E1 (CYP 2E1),
      accounting for MG formation during glycolysis, protein, and lipid metabolism,
      respectively, was unchanged/reduced. Fructose (25 mM) treatment of VSMCs up
      regulated the expression of GLUT5 and aldolase B and accelerated MG formation.
      Insulin (100 nM) increased GLUT5 expression and augmented fructose-increased
      cellular fructose accumulation and MG formation. Glucose (25 mM) treatment
      activated the polyol pathway and enhanced fructose formation, leading to aldolase
      B upregulation and MG overproduction. Inhibition of the polyol pathway reduced
      the glucose-increased aldolase B expression and MG generation. The excess
      formation of MG in under these conditions was eliminated by knock-down of
      aldolase B, but not by knock-down of aldolase A or inhibition of SSAO or CYP 2E1.
      CONCLUSION: Upregulation of aldolase B by accumulated fructose is a common
      mechanism for MG overproduction in VSMCs and aorta in different models of
      metabolic syndrome.

PMID- 21890533
TI  - Effectiveness of a college-level self-management course on successful behavior
      change.
AB  - Studies have shown that college-level self-management (SM) courses, which
      typically require students to complete an individual project as part of the
      course, can be an effective method for promoting successful self-change (i.e.,
      targeted behavioral change). However, only a handful of studies have focused on
      and investigated the intensity of the SM component required for successfully
      changing a target behavior. The purpose of this study was to (a) examine the
      effectiveness of a SM course in improving a target behavior within a college
      setting, (b) determine the level of SM course intensity necessary for successful
      behavioral change, and (c) identify the characteristics of successful self
      managers in terms of strategy use. A total of 84 college students were enrolled
      in a high-intensity SM course, low-intensity SM course, or non-SM course (i.e.,
      control group). Self-report questionnaires were administered at the beginning and
      end of the courses. Results showed that only the high-intensity SM course was
      effective for successful behavioral change and helped increase certain
      psychosocial characteristics (e.g., internal locus of control, expectancy of
      success). Overall, successful self-managers used significantly more SM strategies
      than participants who were unable to meet their behavioral goals. Implications
      and limitations are also discussed.

PMID- 21890534
TI  - Gender differences in the prevalence, causes and treatment of high cardiovascular
      risk: findings from the FINRISK Survey.
AB  - BACKGROUND: Concerns have been raised that high cardiovascular (CVD) risk is not
      always recognized in women and treated effectively enough. We aimed to analyze,
      whether there are differences between men and women in the prevalence, underlying
      causes and treatment of high CVD risk. DESIGN: A cross-sectional analysis of data
      from population-based health examination surveys was conducted. METHODS: Pooled
      data from the population-based National FINRISK Surveys from the years 1992,
      1997, 2002 and 2007 were used. Subjects with any of the following were considered
      as having high-risk: history of a major CVD event, prevalent diabetes or 10-year
      risk of CVD >= 20% calculated according to the Framingham equation. RESULTS: We
      identified 835 (46.0% women) high-risk subjects in the age group 25-54 years and
      3587 (27.3% women) in the age group 55-74 years. In the younger age group men had
      more often prevalent CVD (29.3% vs 7.8%, p < 0.001) and were more likely to be
      smokers (46.3% vs 21.4%, p < 0.001), whereas women had more diabetes (94.0 % vs
      60.5%, p < 0.001). Younger women were less likely to achieve the recommended
      total cholesterol level of <4.5 mmol/l (14.3 % vs 17.3 %, p = 0.03) and had a
      lower rate of hypolipidaemic therapy (9.6% vs 21.2%, p < 0.001) and
      acetylsalicylic acid therapy (8.3% vs 27.7%, p < 0.001). CONCLUSION: Among young
      individuals, high CVD risk was almost as common in women as in men. It appears
      that the high-risk situation is not always recognized and treated adequately in
      young women.

PMID- 21890535
TI  - Plasma calprotectin levels reflect disease severity in patients with chronic
      heart failure.
AB  - BACKGROUND: Low-grade inflammation has been associated with cardiovascular
      disease (CVD) and chronic heart failure (CHF). The aim of the present study was
      to investigate the potential usefulness of the inflammatory protein calprotectin
      as a biomarker in CHF. METHODS: Plasma calprotectin was measured in 193 CHF
      patients with left ventricular function <45% and in 100 healthy controls at
      baseline. Patients with CHF were followed for a median period of 2.6 years
      according to mortality. RESULTS: The levels of plasma calprotectin were
      significantly increased in the CHF patients compared to the control group (P <
      0.01), primarily due to elevated levels in the patients with New York Heart
      Association (NYHA) class III and IV. Furthermore, plasma calprotectin was a
      superior biomarker of high NYHA classes than other parameters reflecting CHF
      severity, OR 2.2 (1.1-4.3) (P = 0.019). After the follow-up period, 46 patients
      had died. Plasma calprotectin levels did not predict mortality in CHF patients.
      CONCLUSIONS: Plasma calprotectin is increased in CHF patients, indicating that
      inflammatory activity is upregulated in CHF and may be associated with the
      severity of CHF.

PMID- 21890536
TI  - Neomacrolides in the treatment of patients with severe asthma and/or
      bronchiectasis: a retrospective observational study.
AB  - RATIONALE: Previous studies have demonstrated that long-term low-dose macrolides
      are efficacious in cystic fibrosis (CF) and diffuse panbronchiolitis, two chronic
      neutrophilic airway diseases. AIMS: The aims of this study were to evaluate the
      efficacy and safety of low-dose neomacrolides as add-on therapy in patients with
      severe asthma and/or bronchiectasis and to identify predictors for therapeutic
      response. METHODS: In a retrospective observational cohort study, we examined 131
      adult, non-CF patients with severe asthma and/or bronchiectasis, receiving low
      dose neomacrolides as add-on treatment. Pulmonary function tests and symptom
      scores were assessed at baseline and after 3 to 8 weeks of therapy. RESULTS:
      After 3-8 weeks of treatment with low-dose neomacrolides, 108 patients were
      available for evaluation. In asthma patients (n = 47), pulmonary function tests
      and symptom scores improved significantly. Responders (>=7% forced expiratory
      volume in one second predicted [FEV(1)%] improvement) were older (55 vs. 47
      years; p = 0.042) and had a longer duration of asthma (29 vs. 9 years; p =
      0.052). In patients with bronchiectasis only (n = 61), symptom scores improved
      significantly. Responders (>=60% symptom score improvement) were older (61 vs. 53
      years; p = 0.004), more frequently male (53% vs. 27%; p = 0.043), and there was a
      nonsignificant trend towards higher high-resolution CT (HRCT) score for
      bronchiectasis in responders (6.4 vs. 4.6; p = 0.053). In multivariate logistic
      regression analysis, age and male gender were independent predictors for
      improvement in this group. CONCLUSION: The results of this retrospective study
      suggest that neomacrolides may be useful as an add-on therapy in patients with
      severe asthma and/or bronchiectasis. Older age may predict good response in
      patients with severe asthma, whereas older age, male gender and a higher HRCT
      score for bronchiectasis may predict therapeutic response in patients with
      bronchiectasis only. Prospective controlled trials of neomacrolides in patients
      with severe asthma are needed to confirm these observations.

PMID- 21890537
TI  - 'Sentinel' mutations in standard population sequencing can predict the presence
      of HIV-1 reverse transcriptase major mutations detectable only by ultra-deep
      pyrosequencing.
AB  - OBJECTIVES: This proof-of-concept study aimed to identify whether mutations
      considered not yet relevant for drug resistance (but located at key drug
      resistance positions) can act as 'sentinels' of minority resistant variants in
      HIV-1 drug-naive patients. METHODS: We focused our attention on three reverse
      transcriptase (RT) mutations (T69S, L210M and K103R) easily detected by standard
      population sequencing [i.e. the genotypic resistance test (GRT)]. Ultra-deep
      pyrosequencing (UDPS) of HIV-1 RT was performed using GS-FLX Roche, on plasma RNA
      from 40 drug-naive patients infected with HIV-1 subtype B without primary
      resistance detected by GRT. Only RT drug resistance mutations detected at >0.1%
      in both forward and reverse directions were considered. Associations between GRT
      sentinel mutations and UDPS drug resistance were assessed using Fisher's exact
      test. RESULTS: UDPS detected drug resistance mutations in 18/40 drug-naive
      patients. Patients carrying HIV-1 strains with T69S and L210M by GRT showed a
      trend to greater infection by minority drug-resistant variants than control
      patients infected by HIV-1 without these mutations (5/10 and 7/10 versus 3/10; P
      = not significant). No association was found for K103R by GRT. Notably, T69S and
      L210M (but not K103R or control viruses) were associated with GRT minority drug
      resistant variants with a prevalence >1% (3/10 and 4/10 versus 0/20 in K103R and
      controls; P = 0.03 and P = 0.008, respectively). Moreover, the presence of L210M
      or T69S viruses by GRT significantly correlated with that of minority thymidine
      analogue mutations by UDPS (6/20 patients carrying HIV-1 strains with T69S/L210M
      versus 0/20 patients carrying HIV-1 having K103R or none of these mutations; P =
      0.03). CONCLUSIONS: This proof-of-concept study suggests the existence of genetic
      markers, detectable by routine testing, potentially acting as sentinel mutations
      of minority drug resistance. Their identification may help in the selection of
      patients at high risk of resistance in reservoirs without the necessity of using
      UDPS.

PMID- 21890538
TI  - Plasma concentrations of efavirenz are associated with body weight in HIV
      positive individuals.
AB  - BACKGROUND: Efavirenz is among the most widely used antiretroviral drugs.
      Increased efavirenz exposure has been associated with CNS side effects and also
      with the chance of emergence of resistance upon treatment interruptions. The
      objective of this study was to evaluate factors associated with efavirenz plasma
      concentrations in a cohort of HIV-infected individuals. METHODS: From July 2009
      to March 2010, HIV-infected patients with efavirenz as part of antiretroviral
      therapy (600 mg at night), undetectable viral load for at least 1 year and CD4
      cell count >200 cells/mm(3) were consecutively enrolled at the HIV/AIDS
      ambulatory care unit in southern Brazil. Plasma samples were taken 18-23 h after
      efavirenz last dose and analysed by validated ultra-performance liquid
      chromatography. RESULTS: Forty-one subjects were included (21 females). Mean age
      and weight were 45.4 years and 70.9 kg, respectively. Mean efavirenz plasma
      concentration was 2.20 +/- 2.17 mg/L. Most plasma concentrations (73%) were
      within the therapeutic window (1-4 mg/L); 17% were below and 10% above the
      limits. There were no significant associations between efavirenz concentration
      and age, CD4 cell count, time on antiretroviral treatment and gender. There was
      significant and inverse correlation between efavirenz concentrations and body
      weight (P = 0.013) and body mass index (P = 0.001). CONCLUSIONS: In this cohort
      of well-controlled HIV-positive individuals, patients with lower weight or body
      mass index had a higher chance of presenting elevated plasma concentrations of
      efavirenz. Therapeutic drug monitoring to adjust dose might be a helpful tool to
      decrease efavirenz dose in order to minimize costs and adverse effects.

PMID- 21890540
TI  - Dropout from computer-based interventions for children and adolescents with
      chronic health conditions.
AB  - Dropout is a frequent problem in face-to-face psychological interventions.
      However, little is known regarding dropout in computer-based interventions
      (CBIs). It is important to understand the extent to which children and
      adolescents drop out of CBIs, so we can ensure that more people complete the
      programmes to gain maximum benefit. A systematic review of current research on
      dropout from CBIs identified 15 studies. Dropout rate ranged from 0 per cent to
      54 per cent with a median of 15 per cent. There is a need for more rigorous
      investigation of the extent of, and reasons for, dropout from CBIs with children
      and adolescents with chronic health conditions.

PMID- 21890541
TI  - Infectious syphilis in young heterosexuals: responding to an evolving epidemic.

PMID- 21890539
TI  - Bevacizumab impairs oxidative energy metabolism and shows antitumoral effects in
      recurrent glioblastomas: a 31P/1H MRSI and quantitative magnetic resonance
      imaging study.
AB  - Bevacizumab shows unprecedented rates of response in recurrent glioblastomas
      (GBM), but the detailed mechanisms are still unclear. We employed in vivo
      magnetic resonance spectroscopic imaging (MRSI) and quantitative magnetic
      resonance imaging to investigate whether bevacizumab alters oxygen and energy
      metabolism and whether this effect has antitumoral activity in recurrent GBM.
      (31)P and (1)H MRSI, apparent diffusion coefficient (ADC), and high-resolution T2
      and T2' mapping (indirect marker of oxygen extraction) were investigated in 16
      patients with recurrent GBM at 3 Tesla before and 1.5-2 months after initiation
      of therapy with bevacizumab. Changes of metabolite concentrations and of the
      quantitative values in the tumor and normal appearing brain tissue were
      calculated. The Wilcoxon signed-ranks test was used to evaluate differences for
      tumor/edema versus control as well as changes before versus after commencement of
      therapy. Survival analyses were performed for significant parameters. Tumor T2',
      pH, ADC, and T2 decreased significantly in patients responding to bevacizumab
      therapy (n = 10). Patients with at least 25% T2' decrease during treatment showed
      longer progression-free and overall survival durations. Levels of high-energy
      metabolites were lower at baseline; these persisted under therapy.
      Glycerophosphoethanolamine as catabolic phospholipid metabolite increased in
      responders. The MRSI data support the hypothesis that bevacizumab induces
      relative tumor hypoxia (T2' decrease) and affects energy homeostasis in recurrent
      GBM, suggesting that bevacizumab impairs vascular function. The antiangiogenic
      effect of bevacizumab is predictive of better outcome and seems to induce
      antitumoral activity in the responding GBMs.

PMID- 21890542
TI  - Dysaesthetic penoscrotodynia: nomenclature, classification, diagnosis and
      treatment.
AB  - Male patients can present with a genital skin burning sensation that bears
      similarities to vulvodynia. The classification of vulvodynia by International
      Society for the Study of Vulvovaginal Disease of vulvodynia provides a blueprint
      for nomenclature and classification of Dysaesthetic penoscrotodynia (DPSD).
      Recognizing DPSD as generalized, localized, provoked, unprovoked and mixed will
      enable precise and objective communication between practitioners. Learning from
      research on the aetiology and management of vulvodynia can improve the care of
      patients suffering with DPSD. Scope remains for better acknowledgement of DPSD
      within the medical profession and improvement in its public profile in order to
      enhance patient care.

PMID- 21890543
TI  - The public health response to the re-emergence of syphilis in Wales, UK.
AB  - During the 1990s, cases of infectious syphilis were uncommon in Wales. In 2002,
      an outbreak occurred in a sexual network of men who have sex with men (MSM)
      attending a sauna. A multidisciplinary outbreak control team was convened to
      raise awareness of the outbreak among MSM and health professionals, assess the
      extent of outbreak, and initiate surveillance measures. It is likely that early
      intensive control efforts dampened the epidemic curve. However, since 2006 the
      number of cases has increased steadily to a peak of four cases per 100,000
      population in 2008. The majority of cases continue to occur in MSM (81% in 2009)
      and in those attending genitourinary (GU) medicine clinics in south east Wales
      (76%). Traditional sexual networks such as saunas, bars/clubs and cruising
      grounds remain frequently reported, but Internet-based networks are assuming
      increasing importance. Public health interventions have been sustained, using
      traditional partner notification, health promotion initiatives, and more
      innovative Internet network tracing methods.

PMID- 21890544
TI  - Syphilis resurgence in Dublin, Ireland.
AB  - A large outbreak of syphilis was reported in Dublin, Ireland, in 2001. The mean
      age of patients in 2001 was 35 years and 22.5% of patients were HIV-positive. The
      number of new cases decreased from 2003 on, however, new diagnoses have again
      increased. All positive syphilis serology results from 2007-09 were identified.
      Patients were included if they had a newly positive syphilis serology or, in the
      case of patients with previously treated syphilis, had a four-fold rise in rapid
      plasma reagin titre. Four hundred and thirty-nine new diagnoses of syphilis were
      made. The mean age of patients at diagnosis was 35.7 years (range 17-73 years).
      Four hundred and twelve (93.8%) cases occurred in men. Three hundred and eighty
      one (86.8%) cases occurred in men who have sex with men (MSM). The estimated
      crude incidence rate among MSM is 378.16 per 100,000 population. Where known,
      126/421 (28.7%) occurred in HIV-positive patients. Sixty-eight (15.5%) episodes
      of syphilis infection were diagnosed in patients who had had previously been
      diagnosed and treated for syphilis; 43/68 (63.2%) cases of re-infection occurred
      in HIV-positive patients. The rising number of syphilis diagnoses and high
      associated HIV co-infection rate is concerning and prevention efforts must
      continue to decrease the number of new syphilis cases.

PMID- 21890545
TI  - Survival of HIV-infected patients admitted to the intensive care unit in the era
      of highly active antiretroviral therapy.
AB  - We retrospectively studied outcomes for HIV-infected patients admitted to the
      intensive care unit (ICU) between January 1999 and June 2009. Patient
      demographics, receipt of highly active antiretroviral therapy (HAART), reason for
      ICU admission and survival to ICU and hospital discharge were recorded.
      Comparison was made against outcomes for general medical patients
      contemporaneously admitted to the same ICU. One hundred and ninety-two HIV
      infected patients had 222 ICU admissions; 116 patients required mechanical
      ventilation (MV) and 43 required renal replacement therapy. ICU admission was due
      to an HIV-associated diagnosis in 113 patients; 37 had Pneumocystis pneumonia.
      Survival to ICU discharge and hospital discharge for HIV-infected patients was
      78% and 70%, respectively, and was 75% and 68% among 2065 general medical
      patients with 2274 ICU admissions; P = 0.452 and P = 0.458, respectively. HIV
      infection was newly diagnosed in 42 patients; their ICU and hospital survival was
      69% and 57%, respectively. From multivariable analysis, factors associated with
      ICU survival were patient's age (odds ratio [OR] = 0.74 [95% confidence interval
      (CI) = 0.53-1.02] per 10-year increase), albumin (OR = 1.05 [1.00-1.09] per 1
      g/dL increase), Acute Physiology and Chronic Health Evaluation (APACHE) II score
      (OR = 0.55 [0.35-0.87] per 10 unit increase), receipt of HAART (OR = 2.44 [1.01
      4.94]) and need for MV (OR = 0.14 [0.06-0.36]). In the era of HAART, HIV-infected
      patients should be offered ICU admission if it is likely to be of benefit.

PMID- 21890547
TI  - A cluster of infectious syphilis among young heterosexuals in south-east
      Hampshire.
AB  - A small cluster of infectious syphilis among young heterosexuals aged under 25
      years in south-east Hampshire has highlighted the limitations of effective
      partner notification, the challenges of providing effective awareness raising and
      the need for increased accessibility to genitourinary (GU) medicine services.
      Evaluation of awareness raising to both the target age group and health care
      professionals indicated that the strategies employed did not increase testing and
      had limited impact on young people in terms of seeking further information.

PMID- 21890546
TI  - Voluntary counselling and testing sites as a source of sentinel information on
      HIV prevalence in a concentrated epidemic: a pilot project from Indonesia.
AB  - A new system for monitoring HIV voluntary counselling and testing (VCT) outcomes
      was established in 2007 at seven VCT clinics in Jakarta and Bali, Indonesia.
      Counsellors collected demographic and risk information from VCT clients. Logistic
      regression was used to determine factors associated with HIV infection. In 15
      months, HIV prevalence in 5569 new clients without HIV symptoms was 63.3% in
      injecting drug users (IDUs) (n = 783), 7.7% in female sex workers (n = 1437),
      31.6% among transgender people (n = 395), 9.3% in men who have sex with men (n =
      268), 13.5% in clients of sex workers (n = 643), 21.1% in people with high-risk
      partners (n = 569) and 3.2% in other VCT clients (n = 822). Among IDUs, being
      older, tested though outreach, tested due to being 'at risk' and having injected
      for one or more years were independently associated with HIV infection. This
      network confirmed high HIV prevalence among IDUs and transgender people. HIV
      prevalence estimates were consistent with serosurveys.

PMID- 21890548
TI  - An ongoing outbreak of heterosexually-acquired syphilis across Teesside, UK.
AB  - Prior to 2006, diagnoses of heterosexually acquired syphilis were rare in
      Teesside (an area in the north east of England, UK). Since 2006, there has been
      an increase in such cases, with 24 cases diagnosed in 2006 and 22 in 2007. There
      was a marked reduction in cases in 2008 with six cases reported, but a large
      increase in diagnoses in 2009 (34 cases). There have been 14 cases to date in
      2010. Of concern is the increase noted in women and younger age groups.
      Geographical mapping of cases shows a wide dispersion across Teesside although
      some clusters were identified, mostly in areas of high deprivation. Little
      detailed information is available to help identify social and sexual networks
      widely and target intervention. A multiagency outbreak control team is addressing
      this problem, based on the principles of partner notification, increased
      awareness, increased screening and health promotion activities. A range of
      measures, including a detailed communications plan, have been implemented.

PMID- 21890549
TI  - Heterosexual transmission of infectious syphilis in central Scotland, 2009.
AB  - A local outbreak of infectious syphilis among heterosexual men and women was
      noted among residents of a National Health Services board in central Scotland in
      2009. This is the first, and remains the only, such outbreak in Scotland
      reporting transmission in the heterosexual population. It was characterized by
      the young age of those infected. This highlights the need for increasing
      knowledge and awareness of syphilis infection among this group.

PMID- 21890550
TI  - An outbreak of infectious syphilis among young heterosexuals in an English town.
AB  - We describe a recent outbreak of syphilis in young heterosexuals in the north
      west of England. A cluster of 12 cases of syphilis (7 primary and 5 early latent)
      was identified in Rochdale in heterosexuals aged 20 or under. Nine were women.
      Five were asymptomatic at presentation. This outbreak occurred in a group not
      usually associated with syphilis transmission in the north west. Not all the
      identified cases could be linked, and so potentially this outbreak is a sentinel
      of a larger problem.

PMID- 21890551
TI  - Investigation of a cluster of syphilis among heterosexuals in an English town.
AB  - A cluster of five (3 primary and 2 early latent) cases of syphilis were
      identified in young heterosexuals in the east of England. Three were symptomatic
      at presentation. No further cases linked to this cluster have been diagnosed
      since June 2010. Effective partner notification is key to the identification and
      treatment of infected contacts.

PMID- 21890552
TI  - Sexual health in general practice: do practitioners comply with the sexually
      transmitted infections guidelines for management of suspected chlamydial
      infections?
AB  - Escalating notifications of chlamydia in Western Australia (WA) prompted an audit
      of the compliance of general practitioners (GPs) with the current guidelines for
      management. The audit consisted of a telephone survey of GPs known to have
      treated a case of chlamydia. GPs generally performed opportunistic screening well
      and complied with the guidelines for testing and treatment. Only 8% of GPs took a
      comprehensive sexual history from symptomatic cases, 53% routinely tested for
      blood-borne sexually transmitted infections and 29% recorded a discussion of
      partner notification in the medical records. The results of the audit form part
      of the review of the current edition of the guidelines, and will be noted in the
      plans for promotion and dissemination of the next edition.

PMID- 21890553
TI  - Use of Telephonetics RESULTS computer-facilitated telephone system with automatic
      results upload.
AB  - Our genitourinary medicine service implemented an automated telephone results
      system in 2010. This system is used in other services but few are able to upload
      negative results automatically from laboratory software. The use of this system
      reduced unanswered calls to a telephone results line and also the number of calls
      that had to be connected to clinical staff. Patients have better access to their
      results in a timely manner, as per the requirements of the recent Standards for
      the Management of Sexually Transmitted Infections document.

PMID- 21890554
TI  - Primary syphilis of the urethral meatus complicated by urethral stricture.
AB  - A 27-year-old man who has sex with men presented with a painful lesion at the
      urethral meatus. A diagnosis of genital herpes was suspected, and initial tests
      for sexually transmitted infections (STIs), including syphilis serology, were
      negative. However, a polymerase chain reaction (PCR) swab for Treponema pallidum
      from the lesion was positive, and a diagnosis of chancre of primary syphilis at
      the meatus was made. Subsequently, the patient required urological surgery due to
      the formation of a urethral stricture. Chancre at the meatus and development of
      stricture are unusual complications of syphilis that may become more common in
      the future with increasing case numbers. We also discuss the development of PCR
      as a useful test for early primary syphilis.

PMID- 21890555
TI  - Early syphilis in a man with a negative Treponema pallidum enzyme immunoassay
      IgM.
AB  - Most serological tests for syphilis rely on an individual's ability to produce
      antibodies. A single screening test may be unreliable for screening in those with
      primary immunodeficiency. We present the first reported case of primary and
      secondary syphilis with negative Treponema pallidum enzyme immunoassay-IgM and
      Venereal Disease Research Laboratory tests in a man with common variable
      immunodeficiency.

PMID- 21890556
TI  - The gumma and the gonad: syphilitic orchitis, a rare presentation of testicular
      swelling.
AB  - A 47-year-old man presented to his general practitioner (GP) with painful
      swelling of his right testis. He was diagnosed with epididymo-orchitis and a two
      week course of erythromycin 500 mg four times daily was prescribed by his GP.
      Despite initial improvement, his symptoms persisted and he was referred to the
      local urology department. His sexual history revealed one lifetime sexual
      contact. A midstream urine sample grew non-lactose fermenting coliforms sensitive
      to ciprofloxacin and a two-week course of ciprofloxacin 500 mg two times daily
      was prescribed. Despite clinical improvement, a persistent suspicious abnormality
      on the ultrasound scan of his right testis prompted a right radical inguinal
      orchidectomy to exclude malignancy. Further diagnostic tests including
      histopathology excluded malignancy but confirmed tertiary syphilis. A
      comprehensive literature search revealed only 11 confirmed cases in the past 59
      years.

PMID- 21890557
TI  - Condyloma acuminatum: atypical presentation during pregnancy.
AB  - Genital warts (condylomata acuminata) are caused by human papillomavirus (HPV)
      and are usually transmitted sexually. We present an atypical case of a vaginal
      wart presenting as a single pedunculated mass protruding outside the vagina in a
      pregnant woman in labour. On examination of the vulva, a soft, pink papilliferous
      growth of 6 * 4 cm size was seen hanging outside the vaginal introitus. Speculum
      examination revealed that the growth was attached to the posterior and lateral
      vaginal wall near the fornix. Genital warts can proliferate during pregnancy due
      to altered immunity and increased blood supply, as seen in this case. Vaginal
      warts can also cause problems during delivery, since they prevent the vagina from
      stretching appropriately.

PMID- 21890558
TI  - Immune restoration Klebsiella lymphadenitis.
AB  - A subset of HIV-infected patients who receive antiretroviral therapy (ART)
      develop immune restoration syndrome. A case of immune restoration Klebsiella
      lymphadenitis is described. Fine needle aspiration cytology remains a useful
      investigative tool in the post-ART era, particularly in the diagnosis of
      persistent generalized lymphadenopathy, infection and malignancy of the lymph
      nodes.

PMID- 21890559
TI  - Is unprotected insertive anal sex a predisposing factor in causing sexually
      transmitted urinary tract infection in men?

PMID- 21890560
TI  - Posterior nutcracker syndrome.
AB  - Renal vein compression syndromes are rare causes of hematuria and can be divided
      into anterior and posterior nutcracker syndrome. When the left renal vein is
      compressed between the aorta and the superior mesenteric artery it causes
      anterior nutcracker syndrome. The posterior nutcracker syndrome is very rare and
      is considered when the left renal vein is compressed between the aorta and
      vertebral column. Symptoms of nutcracker syndromes may include intermittent left
      flank pain associated with hematuria, proteinuria, and sometimes with symptoms of
      pelvic congestion. Diagnosis is often difficult and plan for treatment is always
      challenging and requires careful evaluation of the patient's history and workup
      findings. We present a rare case report of a posterior nutcracker syndrome
      diagnosed in a young lady with long-standing symptoms that required surgical
      intervention.

PMID- 21890561
TI  - Thrombin injection for the treatment of mycotic gluteal aneurysm.
AB  - Gluteal aneurysms are rare entity, whose surgical or endovascular management is
      traditionally challenging. Infectious source being increasingly more common as
      the underlying etiology. We herein describe successful implementation of direct
      thrombin injection as another therapeutic option for these patients.

PMID- 21890562
TI  - Toxicity of cyanuric acid to broilers on hepatic and renal health with and
      without melamine.
AB  - The purpose of this study was to evaluate the toxicity potential of cyanuric acid
      (CYA) and a combination of melamine (MEL) and CYA in broilers. A total of 1200
      male COBB 500 broilers were randomly allocated into 1 of 10 treatment groups by a
      5 * 2 factorial design in a 42-d experiment. The dietary treatments were as
      follows: T(1) to T(5): basal diets with 0, 10, 20, 33.3, and 50 mg CYA per kg
      diet; T(6) to T(10): basal diet with CYA regimens similar to T(1) to T(5) but
      with 100 mg MEL per kg diet. There were 6 replication pens with 20 chicks per
      pen. No differences were observed in alanine transaminase (ALT) and aspartate
      aminotransferase (AST) activities. But on d 22, uric acid (UA) and creatinine
      (Crea) concentrations were significantly greater when birds were fed CYA at 33.3
      mg/kg with MEL 100 mg/kg, and Crea concentration was also higher when birds were
      fed CYA at 50 mg/kg. No crystals were found in kidneys but dilated renal tubules
      and small blood vessel expansion were found in kidneys of birds fed CYA at 50
      mg/kg and CYA at 33.3 mg/kg with MEL 100 mg/kg. The apoptosis rate (AR) of
      kidneys of all birds fed CYA and MEL contaminated diets were higher than the
      control group. These results indicated that the dietary addition of CYA and MEL
      could induce kidney damage, and the effects were harmful when the ratio of
      CYA/MEL was 1:3.

PMID- 21890564
TI  - What is the best way to deliver subcutaneous insulin to infants, children, and
      young people with type 1 diabetes mellitus?

PMID- 21890565
TI  - There IT goes again.

PMID- 21890566
TI  - UK access to primary angioplasty services is still highly variable.

PMID- 21890567
TI  - US commission recommends increased protection for people in research after
      reviewing 1940s syphilis study.

PMID- 21890568
TI  - UK peers call for extra investment in HIV and AIDS services.

PMID- 21890569
TI  - "The end of good luck''--long-term survival without anticoagulation: a case
      report and review of the literature.
AB  - Long-term anticoagulation in patients with metallic prosthetic valve disease is
      required according to current guidelines. We describe a patient with a
      functioning mitral mechanical valve without anticoagulation for 27 years. A 46
      year-old man admitted to the emergency department with complains of palpitation.
      The patient had a mitral valve replacement because of severe mitral stenosis. He
      discontinued warfarin treatment 1 month after surgery because of the
      unavailability of this drug in Turkey. Transthoracic echocardiography revealed
      functioning metalic mitral valve with a mean gradient of 9 mm Hg. Fluoroscopy
      showed normal excursions of the mechanical mitral valve. Transesophageal
      echocardiography was performed and revealed fresh thrombus formation in the left
      atrial appendix. Admission international normalized ration (INR) level was 1.79.
      Due to the higher INR level and long-term survival, genetic analysis of warfarin
      polymorphism was performed. There was a homozygous mutation in the vitamin K
      epoxide reductase complex 1 (VKORC1) 1173C>T and 1639G>A genotypes. The possible
      explanations of long-term survival and baseline higher INR level were linked to
      the mutation in warfarin metabolism. We also briefly review the literature.

PMID- 21890570
TI  - Probable warfarin and dapsone interaction.
AB  - We describe a case of a 41-year-old woman who was stable for over a year on 22.5
      mg/week of warfarin. At a follow-up visit, her international normalized ratio
      (INR) was found to be supratherapeutic at 3.9. Her only significant change was
      acyclovir initiation for shingles, and clindamycin and dapsone for infection on
      her right foot. An interaction report was run using Micromedex with no
      interactions reported. Sixteen percent of the weekly dose was held and
      maintenance dose was continued. Two weeks later, the INR remained
      supratherapeutic at 4.3, with discontinuation of clindamycin and dapsone, 5 days
      earlier, as the only change. This time an interaction report was run using Lexi
      Comp, which identified an interaction between warfarin and dapsone. The INR has
      been therapeutic and stable since discontinuation of transient factors. It is
      hypothesized that warfarin and dapsone compete for binding on the CYP2C9 and
      CYP3A4 isoenzymes and therefore serum concentration of warfarin was elevated.

PMID- 21890571
TI  - Hemostasis research in India: past, present, and future.
AB  - Hemostasis research in India has a long history considering the fact that it is
      one of the youngest specialities in the world. If we take creation of prothrombin
      time (PT) test as one of the beginning of modern hemostsis research, then the
      specialty is no older than 60 years. School of Tropical Medicine Kolkata, Banaras
      Hindu University, All India Institute of Medical Sciences at Delhi, Christian
      Medical College at Vellore, Post Graduate Institute of Medical Education and
      Research at Chandigarh, and KEM Hospital at Mumbai contributed substantially in
      defining various bleeding disorders in our country. Unfortunately, some of these
      institutes are no longer as active in the field as they used to be. Currently,
      the Institute of Immunohaematology at Mumbai, Chrstian medical College at
      Vellore, and All India Institute of Medical Sciences at Delhi are actively
      engaged in hemostsis research in India. Developing prenatal diagnostic
      technologies, mutation detection of various hemostatic disorders, developing low
      cost management technologies for hemophilia, and other bleeding disorders are
      becoming important present day research activity in the area of hemostasis in
      addition to age old areas of prevalence and unusual case description studies.
      Entry of many new corporate hospitals, development of structured postgraduate
      training program in hematology, and easy availability of instruments and reagents
      are likely to foster further growth in this area of medical research in India in
      future.

PMID- 21890572
TI  - Labour government's increased NHS spend produced better health outcomes, study
      finds.

PMID- 21890573
TI  - Long-term exposure to air pollution and asthma hospitalisations in older adults:
      a cohort study.
AB  - BACKGROUND: Exposure to air pollution in early life contributes to the burden of
      childhood asthma, but it is not clear whether long-term exposure to air pollution
      can lead to asthma onset or progression in adulthood. OBJECTIVES: The authors
      studied the effect of exposure to traffic-related air pollution over 35 years on
      the risk for asthma hospitalisation in older people. METHODS: 57 053 participants
      in the Danish Diet, Cancer and Health cohort, aged 50-65 years at baseline (1993
      1997), were followed up for first hospital admission for asthma until 2006, and
      the annual nitrogen dioxide (NO(2)) levels were estimated as a proxy of the
      exposure to traffic-related air pollution at the residential addresses of the
      participants since 1971. The association between NO(2) and hospitalisation for
      asthma was modelled using Cox regression, for the full cohort and in people with
      and without previous hospitalisations for asthma, and the effect modification by
      comorbid conditions was assessed. RESULTS: During 10.2 years' median follow-up,
      977 (1.9%) of 53 695 eligible people were admitted to hospital for asthma: 821
      were first-ever admissions and 176 were readmissions. NO(2) levels were
      associated with risk for asthma hospitalisation in the full cohort (HR and 95% CI
      per IQR, 5.8 MUg/m(3): 1.12; 1.04-1.22), and for first-ever admissions (1.10;
      1.01-1.20), with the highest risk in people with a history of asthma (1.41; 1.15
      2.07) or chronic obstructive pulmonary disease (COPD) (1.30; 1.07-1.52)
      hospitalisation. CONCLUSIONS: Long-term exposure to traffic-related air pollution
      increases the risk for asthma hospitalisation in older people. People with
      previous asthma or COPD hospitalisations are most susceptible.

PMID- 21890574
TI  - Grey matter atrophy in cognitively impaired Parkinson's disease.
AB  - OBJECTIVE: Mild cognitive impairment and dementia are common non-motor features
      of Parkinson's disease (PD). The aim of this study was to characterise grey
      matter changes associated with clearly defined stages of cognitive impairment in
      PD using structural MRI. METHODS: 96 PD subjects were classified using detailed
      cognitive testing as PD with normal cognition (PD-N, n=57), PD with mild
      cognitive impairment (PD-MCI, n=23) or PD with dementia (PD-D, n=16); 34 controls
      matched for mean age and sex ratio also participated. Grey matter volume
      differences were evaluated using voxel based morphometry of grey matter segments
      derived from T1 weighted 3 T MRI, and multiple linear regression assessed the
      relationship between cognitive and motor impairments and grey matter
      concentration. RESULTS: Compared with controls, no grey matter differences were
      found in PD-N. PD-MCI showed limited grey matter atrophy in the temporal,
      parietal and frontal cortex as well as the bilateral caudal hippocampus, amygdala
      and right putamen. PD-D subjects exhibited far more extensive atrophy in regions
      involved in PD-MCI but also had reduced grey matter volume in other large areas
      of the temporal lobe (including the parahippocampi), the intracalcarine and
      lingual gyri, posterior cingulate gyrus, frontal regions and bilateral caudate.
      Grey matter loss in PD correlated with global cognitive score but not motor
      impairment in most of these regions. INTERPRETATION: Marked grey matter atrophy
      occurs in PD with dementia but far less extensive changes are evident in PD-MCI.
      Some grey matter atrophy precedes the development of dementia but may be
      accelerated once frank dementia begins.

PMID- 21890575
TI  - Deep brain stimulation in early stage Parkinson's disease: operative experience
      from a prospective randomised clinical trial.
AB  - BACKGROUND: Recent evidence suggests that deep brain stimulation of the
      subthalamic nucleus (STN-DBS) may have a disease modifying effect in early
      Parkinson's disease (PD). A randomised, prospective study is underway to
      determine whether STN-DBS in early PD is safe and tolerable. OBJECTIVES/METHODS:
      15 of 30 early PD patients were randomised to receive STN-DBS implants in an
      institutional review board approved protocol. Operative technique, location of
      DBS leads and perioperative adverse events are reported. Active contact used for
      stimulation in these patients was compared with 47 advanced PD patients
      undergoing an identical procedure by the same surgeon. RESULTS: 14 of the 15
      patients did not sustain any long term (>3 months) complications from the
      surgery. One subject suffered a stroke resulting in mild cognitive changes and
      slight right arm and face weakness. The average optimal contact used in
      symptomatic treatment of early PD patients was: anterior -1.1+/-1.7 mm, lateral
      10.7+/-1.7 mm and superior -3.3+/-2.5 mm (anterior and posterior commissure
      coordinates). This location is statistically no different (0.77 mm, p>0.05) than
      the optimal contact used in the treatment of 47 advanced PD patients.
      CONCLUSIONS: The perioperative adverse events in this trial of subjects with
      early stage PD are comparable with those reported for STN-DBS in advanced PD. The
      active contact position used in early PD is not significantly different from that
      used in late stage disease. This is the first report of the operative experience
      from a randomised, surgical versus best medical therapy trial for the early
      treatment of PD.

PMID- 21890576
TI  - Survey of non-invasive ventilation use in ALS in Britain.

PMID- 21890577
TI  - Cortical pathology in multiple sclerosis patients with epilepsy: a 3 year
      longitudinal study.
AB  - INTRODUCTION: The cause of epilepsy in multiple sclerosis (MS) has not yet been
      elucidated. The relevance of cortical pathology (cortical lesions and thickness)
      in MS patients with and without epilepsy was evaluated in a longitudinal study.
      METHODS: 32 relapsing-remitting MS patients with epilepsy (RRMS/E) and 60 matched
      RRMS patients without epilepsy were included in a 3 year longitudinal study. The
      following clinical and MR parameters were analysed: Expanded Disability Status
      Scale (EDSS), cognitive score (CS), cortical lesion (CL) number and volume, grey
      matter fraction (GMf), global cortical thickness (CTh), T2 white matter lesion
      volume (T2WMLV), new CLs and new WM lesions. RESULTS: At baseline (T0), CLs were
      observed in 27/32 (84.4%) RRMS/E and in 26/60 (43.3%) RRMS (p<0.001) patients,
      and the RRMS/E group had a higher number (10.2 +/- 8.9 vs 4.5 +/- 2.4; p<0.001)
      and total volume (2.0 +/- 1.3 vs 0.7 +/- 0.8 cm(3); p<0.001) of CLs compared with
      the RRMS group. No significant difference in T2WMLV was observed. Global CTh was
      lower in RRMS/E (2.12 +/- 0.19 vs 2.35 +/- 0.14 mm; p<0.001), and this group also
      showed a decline in cognition (CS 10.9 +/- 6.3 vs 6.2 +/- 3.5; p<0.001). After 3
      years (T1), the RRMS/E group had a higher accumulation of new CLs (3.4 +/- 3.2 vs
      1.2 +/- 1.1; p<0.001) and faster reduction of GMf (p=0.022) while the two groups
      did not differ in the number of new WM and new Gad+ lesions. DISCUSSION: RRMS/E
      had a more severe and rapidly evolving cortical pathology (CLs and atrophy)
      compared with RRMS without epilepsy. The RRMS/E group was also characterised by
      more pronounced cognitive decline, higher EDSS and higher prevalence of men.

PMID- 21890578
TI  - Bicyclist deaths and striking vehicles in the USA.
AB  - OBJECTIVES: Bicycling is a popular means of transportation that is sometimes
      associated with injury from collisions. The authors analysed national data for
      the USA to evaluate bicyclist deaths associated with motor vehicle impacts.
      METHODS: The authors conducted a population-based case-control analysis of road
      deaths reported by the National Highway Traffic Safety Administration. The
      authors included bicyclist deaths from 1 January 2008 to 31 December 2008
      (cases), along with the non-bicyclist road deaths immediately before and after
      the bicyclist death in the same state (controls). Analyses also included linkages
      to auto appraisal websites to estimate type, size and cost of the motor vehicle
      involved in each death. RESULTS: A total of 711 bicyclist deaths were included,
      equivalent to a rate of 2 deaths per million population annually. No state had a
      rate statistically significantly below the national average whereas Florida was a
      high outlier with three times the national rate (p<0.001). The typical bicyclist
      who died was a man travelling in the afternoon or evening. The average estimated
      resale value of the involved motor vehicle was about one-third higher for
      bicyclist deaths than control deaths (US$10 603 vs US$8118, p<0.001). Analyses
      based on median estimated resale value and luxury resale value yielded similar
      findings. Stratified analyses based on demographics, time and posted speed limits
      yielded similar discrepancies. Larger motor vehicles were particularly common in
      bicyclist deaths compared to control deaths, especially freight trucks (11% vs
      8%, p=0.008) and large automobiles (43% vs 37%, p=0.004). Conversely, motorcycles
      were distinctly infrequent in bicyclist deaths compared to control deaths (1% vs
      14%, p<0.001). CONCLUSIONS: Large expensive motor vehicles account for a
      disproportionate share of bicyclist deaths. Bicyclists, motorists, policy-makers
      and vehicle manufacturers need to consider more imaginative solutions to help
      prevent future deaths.

PMID- 21890579
TI  - Preventing unintentional injuries to children under 15 years in the outdoors: a
      systematic review of the effectiveness of educational programs.
AB  - INTRODUCTION: Unintentional injuries to children in the outdoors have a
      significant impact on child mortality, development and healthcare costs. This
      paper presents the findings of a systematic review about the effectiveness of
      programs that provided information, advice or education about the prevention of
      unintentional injuries to children under 15 years during outdoor play and
      leisure. METHODS: A structured search strategy was conducted in a range of
      databases. All report titles and abstracts were screened using pre-defined
      criteria. Included reports were quality appraised using a modified Graphical
      Appraisal Tool for Epidemiological studies (GATE) tool. All quality appraisals
      and data extraction were checked by a second reviewer. If not provided in the
      original reports, ORs and mean differences were calculated, where sufficient data
      were available. RESULTS: Twenty-three studies met the inclusion criteria. There
      was a paucity of robust study designs. The majority of studies only reported a
      short-term follow-up of intermediate outcome measures. Only two studies measured
      injury rates; both reported a reduction, but both studies also had considerable
      methodological weaknesses. The five studies that measured the use of protective
      equipment reported mixed results, although there is some evidence that suggests
      that more extensive educational programs (such as health fairs and media
      campaigns) increase their use. The 20 studies that measured behaviour, attitude
      or knowledge outcomes reported highly mixed results. DISCUSSION: Methodological
      weaknesses of the included studies limit support for a particular course of
      action. To better inform policy and practice, future research should (1) use
      robust study designs and (2) not rely on short-term proxy outcome measures.

PMID- 21890580
TI  - Pilot cluster randomised controlled trial of flooring to reduce injuries from
      falls in elderly care units: study protocol.
AB  - Falls are an issue disproportionately affecting older people who are at increased
      risk of falls and injury. This protocol describes a pilot study investigating
      shock-absorbing flooring for fall-related injuries in wards for older people.
      OBJECTIVES: To inform future research by evaluating fall-related injuries on the
      intervention and existing flooring, assessing the sustainability of the flooring
      in ward environments, estimating the cost-effectiveness of the floor and
      assessing how the floor affects patients and other users. DESIGN: This study uses
      mixed methods a pilot cluster randomised controlled trial, observation via
      mechanical testing and interviews. Eight participating wards (clusters) are
      randomised using a computer-generated list. No blinding is incorporated into the
      study. Each site has a baseline period of approximately 6 months. Then, four
      sites receive the intervention floor, while four continue using standard floors.
      Sites are then followed up for approximately 1 year. PARTICIPANTS: Any person
      admitted to a bed in the 'study area' of a participating ward can be entered into
      the trial. Orientated patients, visitors and any hospital staff who use the floor
      in a study area are eligible for inclusion in an interview. INTERVENTION: An 8.3
      mm thick vinyl floor covering with polyvinyl chloride foam backing (Tarkett
      Omnisports EXCEL). OUTCOMES: The primary outcome is fall-related injuries.
      Severity of injuries, falls, cost-effectiveness, user views and mechanical
      performance (shock absorbency and slip resistance) are also being assessed.

PMID- 21890581
TI  - Reducing regional inequality in mortality from road traffic injuries through
      enforcement of the mandatory motorcycle helmet law in Taiwan.
AB  - BACKGROUND: This study was conducted to examine whether passage of the mandatory
      motorcycle helmet law in 1997 reduced the regional inequality in mortality from
      road traffic injuries (RTIs) across 22 cities/counties in Taiwan. METHODS: We
      calculated the absolute (between-group variance, BGV) and relative (rate ratio
      between the city/county with the highest and lowest rate, RR) terms of inequality
      for the overall and motorcycle-related RTI mortality rates, the rate of helmet
      use and three other explanatory factors associated with RTI mortality at the
      city/county level from 1997 through 2008. RESULTS: The BGV of the overall and
      motorcycle-related RTI mortality rates across the 22 cities/counties showed
      persistently decreasing trends from 1997 to 2008; however, the RR of RTI
      mortality first increased and then levelled off from 2002. The decreasing trend
      in inequality was most prominent in males aged 0-24 years. The BGV and RR of the
      rate of motorcycle helmet use decreased after passage of the law but increased
      from 2002 onwards. CONCLUSION: In Taiwan, passage of the mandatory motorcycle
      helmet law reduced the regional inequality in RTI mortality; however, a
      resurgence in regional inequality in the helmet use rate years after passage of
      the helmet law was noted. It is therefore necessary to monitor the helmet use
      rate after passage of such a law to ensure the effect of a reduction in regional
      inequality in RTI mortality.

PMID- 21890582
TI  - Modulation of anxiety behavior in the elevated plus maze using peptidic oxytocin
      and vasopressin receptor ligands in the rat.
AB  - Oxytocin (OT) and arginine vasopressin (AVP), in their capacities as
      neuromodulators, are believed to play an important role in mood control,
      including regulation of the anxiety response. In the present study, the
      contributions of oxytocin and vasopressin receptor modulation to anxiety-like
      behaviors were examined in male Sprague-Dawley rats. The behavioral effects of
      the OT receptor agonist, carbetocin (intracerebroventricular, intravenous and
      intraperitoneal routes), the AVP receptor agonist desmopressin (intravenous
      route), and the OT/AVP(1A) receptor antagonist atosiban (intravenous route) were
      evaluated in the elevated plus maze. The benzodiazepine diazepam was included as
      a positive control. Central but not systemic administration of carbetocin
      produced pronounced anxiolytic-like behavioral changes comparable to those
      measured following systemic diazepam treatment. The anxiolytic efficacy of
      carbetocin was maintained following 10 days of once-daily treatment, contrasting
      with the effects of diazepam which were no longer distinguishable from saline
      treatment. Systemic administration of desmopressin produced anxiogenic-like
      effects whereas systemic atosiban produced anxiolytic-like effects. Co
      administration of desmopressin with atosiban resulted in saline-like behavioral
      responses, implicating an AVP(1A) receptor mechanism in the anxiolytic and
      anxiogenic effects of these neuropeptides following systemic administration. A
      peripherally-mediated antidiuretic effect of desmopressin on water consumption
      was also demonstrated. These results highlight the potential therapeutic utility
      of AVP(1A) receptor blockade in the modulation of anxiety-related behaviors;
      AVP(1A) receptor blockade appears to be a more promising pharmacological target
      than does OT receptor activation following systemic drug administration.

PMID- 21890583
TI  - Alcohol selectively impairs negative self-relevant associations in young
      drinkers.
AB  - The stress-dampening effects of alcohol have been attributed to 'appraisal
      disruption'- decreased ability of stimuli to evoke threatening associations in
      memory. Appraisal disruption could apply to oneself as well as situational
      stimuli. This question was investigated in undergraduate drinkers (n=90/Gender)
      with low or high anxiety sensitivity (AS; n=90/AS Group), a trait linked with
      hyper-vigilance to threat. Subjects received alcohol (0.7 g/kg males; 0.63 g/kg
      females), placebo or soft drink and performed a speech about their appearance.
      Sequence of drink administration and speech advisory (threat) was manipulated
      between subjects: Threat before Drink, Threat after Drink, No-Threat Control. The
      Implicit Association Test measured self-relevant associations based upon time to
      classify positive and negative attribute words (e.g. Cute, Ugly) paired with self
      relevant or non-self-relevant object words (e.g. Me, Them). Alcohol selectively
      slowed negative self-relevant decisions, regardless of other factors. Relative
      fluency of negative versus positive decisions (D) correlated inversely with state
      anxiety and systolic blood pressure immediately before speech performance, and
      correlated directly with severity of alcohol problems. These findings are
      consistent with the Appraisal Disruption hypothesis. Preferential impairment of
      negative self-relevant associations may decrease perceived vulnerability under
      alcohol and increase risk for alcohol problems in young drinkers.

PMID- 21890585
TI  - The effects of TPA023, a GABAAalpha2,3 subtype-selective partial agonist, on
      essential tremor in comparison to alcohol.
AB  - Essential tremor (ET) is a relatively frequent neurological disorder that
      responds in some patients to gamma-aminobutyric acid A (GABA(A)) agonists such as
      the benzodiazepines. Partial subtype-selective GABA(A) agonists may have an
      improved side effect profile compared to non-selective GABA(A) agonists. However,
      it is unknown which GABA(A) subtypes are involved in the therapeutic effects of
      benzodiazepines in ET. The effects of 2 mg TPA023, a GABA(A) alpha2,3 subtype
      selective partial agonist, on ET were compared to the effects of a stable alcohol
      level (0.6 g/L) and placebo in nine patients with ET. Tremor evaluation included
      laboratory accelerometry and a performance-based scale. Additional measurements
      were performed to evaluate other effects on the central nervous system (CNS).
      Alcohol significantly diminished tremor symptoms in the postural and kinetic
      condition, as assessed by laboratory accelerometry, but the performance-based
      rating scale was unaffected. Tremor was also reduced after TPA023 treatment in
      the kinetic condition, albeit not significantly. Additionally, TPA023 decreased
      saccadic peak velocity, while alcohol decreased subjective feelings of alertness.
      This study showed that alcohol reduced maximum tremor power, as assessed by
      laboratory accelerometry, unlike TPA023, which decreased tremor symptoms to some
      extent but not significantly. This study showed that treatment with an alpha2,3
      subunit-selective GABA(A) partial agonist was less effective than a stable level
      of alcohol in reducing ET symptoms. These results provide no support for a
      therapeutic role of TPA023 in the suppression of ET symptoms.

PMID- 21890586
TI  - Effects of positive modulators of alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid (AMPA)-type glutamate receptors in a benzodiazepine
      induced deficit of spatial discrimination in mice.
AB  - Imbalance between GABAergic and glutamatergic neurotransmission has been recently
      hypothesized to trigger memory decline related either to ageing or to Alzheimer's
      disease (AD). Thereby, benzodiazepine-induced anterograde amnesia has been
      construed as a model of hippocampal-related cognitive dysfunctions. Since spatial
      memory is altered both by ageing and by benzodiazepines such as alprazolam, we
      investigated the pharmacological sensitivity of alprazolam-induced deficit in a
      delayed spatial discrimination (SD) task, notably with positive allosteric
      modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
      type glutamate receptors. We showed that alprazolam (0.1 mg/kg intraperitoneally)
      induced memory impairments as compared with vehicle-treated mice. The oral
      administration of modulators of AMPA receptors (IDRA-21: 10 mg/kg; S18986: 3 and
      10 mg/kg) reversed the alprazolam-induced deficits. This study is first to show
      evidence that reference treatments of AD, such as memantine (a NMDA receptor
      antagonist) at 3 mg/kg per os (po) and donepezil (an acetylcholinesterase
      inhibitor) at 1 mg/kg po, also reversed the alprazolam-induced amnesia. Given
      such results, the SD task emerges as a valuable novel task to screen pro
      cognitive compounds. Thus, we highlight the efficacy of modulators of AMPA-type
      glutamate receptors to counteract alprazolam-induced spatial deficits. These
      results could be viewed alongside the imbalance between excitation and inhibition
      observed during normal and pathological ageing.

PMID- 21890584
TI  - Task demands dissociate the effects of muscarinic M1 receptor blockade and
      protein kinase C inhibition on attentional performance in rats.
AB  - The cholinergic system is known to be necessary for normal attentional
      processing. However, the receptors and mechanisms mediating the effects of
      acetylcholine on attention remain unclear. Previous work in our laboratory
      suggested that cholinergic muscarinic receptors are critical for maintaining
      performance in an attention-demanding task in rats. We examined the role of the
      muscarinic M(1) receptor and protein kinase C (PKC), which is activated by the
      M(1) receptor, in attention task performance. Rats were trained in an attention
      demanding task requiring discrimination of brief (500, 100, 25 ms) visual signals
      from trials with no signal presentation. The effects of muscarinic M(1) receptor
      blockade were assessed by administering dicyclomine (0-5.0 mg/kg). The effects of
      PKC inhibition were assessed by administering chelerythrine chloride (0-2.0
      mg/kg). Dicyclomine decreased the accuracy of detecting longer signals in this
      attention task, including when attentional demands were increased by flashing a
      houselight throughout the session. Chelerythrine chloride decreased the accuracy
      of signal detection in the standard version of the task but not when the
      houselight was flashed throughout the session. The present findings indicate that
      muscarinic M(1) receptors are critical for maintaining performance when
      attentional demands are increased, and that PKC activity may contribute to some
      aspects of attentional performance.

PMID- 21890587
TI  - Long-term ovariectomy modulates the antidepressant-like action of estrogens, but
      not of antidepressants.
AB  - Controversial results related to effectiveness of estrogen replacement therapy
      (ERT) to alleviate depression are frequently reported. The discrepancies could be
      related to (a) time when ERT is initiated after the beginning of menopause and/or
      (b) type of estrogen used. Furthermore, estrogens modulate the antidepressant
      effect of different compounds; therefore, the effectiveness of antidepressant
      drugs could also depend on the menopausal status. The aim of the present study
      was to analyze whether the time after estrogen decline can influence
      antidepressant-like effects of two estrogens and/or two antidepressants. Thus,
      the antidepressant-like actions of 17beta-estradiol (E(2)), 17alpha-ethynyl
      estradiol (EE(2)), fluoxetine (FLX) and desipramine (DMI) were studied at
      different periods (1, 3 and 12 weeks) after ovariectomy (OVX), using the forced
      swimming test (FST). Results showed that OVX increased depressive-like behavior
      only 1 week after OVX. The antidepressant-like actions of E(2), but not those of
      EE(2), were cancelled 12 weeks after OVX. Conversely, antidepressant-like actions
      of FLX and DMI were observed at 1, 3 and 12 weeks after OVX. In conclusion, while
      the antidepressant-like effects of estrogens depended on the time at which
      treatment is initiated after OVX as well as on the estrogenic compound used,
      antidepressant-like effects of FLX and DMI were not blocked by OVX.

PMID- 21890588
TI  - The effects of 7.5% carbon dioxide inhalation on task performance in healthy
      volunteers.
AB  - Studies have shown that anxiety can positively or negatively affect performance
      with respect to focusing of attention or distractibility, subjective workload and
      effort (Humphreys and Revelle, 1984). The inhalation of carbon dioxide (CO(2)) is
      associated with physiological and psychological effects of anxiety (Bailey et
      al., 2005) but its effects on performance have rarely been reported. The studies
      reported here looked at the effects of CO(2) inhalation on physiological and
      subjective measures and performance on two tasks. Eight healthy male participants
      completed a tracking task with a reaction time component, and 12 healthy
      participants (six male) completed a complex target identification task. Tasks
      were performed during 20-min inhalations of 7.5% CO(2)/21% O(2)/71.5% N(2)
      mixture or medical air. Continuous heart rate and blood pressure measures were
      taken, in addition to subjective measures of mood and workload. In comparison
      with air, CO(2) increased heart rate and blood pressure, increased subjective
      scores of panic, anxiety, fear, and tension, and reduced subjective scores of
      relaxation and happiness. Attention was focussed when inhaling CO(2) during the
      simple task, and central demand was greater when inhaling CO(2) during the
      complex task. Therefore, inhalation of 7.5% CO(2) produces effects on task
      performance which are consistent with anxiety.

PMID- 21890589
TI  - A clozapine-like effect of cyproheptadine on progressive ratio schedule
      performance.
AB  - The atypical antipsychotic drug clozapine has multiple pharmacological actions,
      some of which, including 5-hydroxytryptamine (5-HT2) and histamine (H1) receptor
      antagonist effects, are shared by the non-selective 5-HT receptor antagonist
      cyproheptadine. Atypical antipsychotics have a characteristic profile of action
      on operant behaviour maintained by progressive ratio schedules, as revealed by
      Killeen's (1994) mathematical model of schedule controlled behaviour. These drugs
      increase the values of a parameter that expresses the 'incentive value' of the
      reinforcer (a) and a parameter that is inversely related to the 'motor capacity'
      of the organism (delta). This experiment examined the effects of acute treatment
      with cyproheptadine and clozapine on performance on a progressive ratio schedule
      of food reinforcement in rats; the effects of a conventional antipsychotic,
      haloperidol, and two drugs with food intake-enhancing effects, chlordiazepoxide
      and Delta9-tetrahydrocannabinol (THC), were also examined. Cyproheptadine (1, 5
      mg kg-1) and clozapine (3.75, 7.5 mg kg-1) increased a and delta. Haloperidol
      (0.05, 0.1 mg kg-1) reduced a and increased delta. Chlordiazepoxide (3, 10 mg kg
      1) increased a but reduced delta. THC (1, 3 mg kg-1) had no effect.
      Interpretation based on Killeen's (1994) model suggests that cyproheptadine and
      clozapine enhanced the incentive value of the reinforcer and impaired motor
      performance. Motor impairment may be due to sedation (possibly reflecting H1
      receptor blockade). Enhancement of incentive value may reflect simultaneous
      blockade of H1 and 5-HT2 receptors, which has been proposed as the mechanism
      underlying the food intake-enhancing effect of cyproheptadine. In agreement with
      previous findings, haloperidol impaired motor performance and reduced the
      incentive value of the reinforcer. Chlordiazepoxide's effect on a is consistent
      with its food intake-enhancing effect.

PMID- 21890590
TI  - The effects of sertindole on sensory gating, sensorimotor gating, and cognition
      in healthy volunteers.
AB  - Sensory gating, indexed by P50 suppression, and sensorimotor gating, indexed by
      prepulse inhibition (PPI), are impaired in schizophrenia spectrum disorders.
      There is considerable evidence that schizophrenia patients treated with atypical
      antipsychotics exhibit relatively less gating deficits than do other patients
      with schizophrenia. Some recent studies have investigated the effects of
      antipsychotic medications on gating in healthy volunteers exhibiting low levels
      of gating, rather than in patients. Therefore, the current study investigated the
      influence of sertindole versus placebo in two separate experimental sessions, on
      PPI, P50 suppression, and cognition in 30 male volunteers stratified for low and
      high baseline gating levels. Sertindole increased PPI and P50 suppression in
      healthy subjects exhibiting low baseline PPI and low baseline P50 suppression,
      respectively, while sertindole attenuated gating in subjects exhibiting high
      baseline gating. Furthermore, subjects exhibiting low PPI chose worse strategies
      in a spatial working memory task. These findings suggest that mixed D(2)/5-HT(2)
      receptor antagonists enhance both PPI and P50 suppression in a way that enhances
      it in healthy subjects exhibiting low baseline gating. Furthermore, the results
      militate in favor of the concomitant assessment of PPI, P50 suppression and
      cognitive measures while investigating the effect of antipsychotic medication in
      healthy subjects.

PMID- 21890591
TI  - Pharmacokinetics and central nervous system effects of the novel dopamine D2
      receptor antagonist JNJ-37822681.
AB  - Using the rate of dissociation from the D(2) receptor as a means to screen novel
      compounds for antipsychotic drug candidates, the centrally acting and fast
      dissociating selective dopamine D(2) receptor antagonist JNJ-37822681 was
      developed. In a blinded, placebo-controlled, randomized first-in-human study, JNJ
      37822681 was administered orally to 27 healthy male volunteers at doses of 0.5,
      2, 5, 10, 15 and 20 mg. Safety, pharmacokinetics and central nervous system
      effects were evaluated by measuring prolactin levels, eye movements, adaptive
      tracking, visual analogue scales, body sway, finger tapping and
      electroencephalography. JNJ-37822681 was well tolerated and somnolence was the
      most frequently reported adverse effect. Peak plasma concentrations increased
      more than proportional to dose, but increases in the area under curve (AUC) were
      dose-proportional. Prolactin elevations started at doses of 5 mg, whereas small
      decreases in adaptive tracking were demonstrated at 10 mg doses. At higher doses,
      JNJ-37822681 caused a small decrease in saccadic peak velocity, smooth pursuit,
      alertness, finger tapping and electroencephalography activity, and an increase in
      body sway. This effect profile is likely to be the result of the selectivity of
      JNJ-37822681 for the D(2) receptor, leading to strong D(2) receptor-mediated
      elevations in serum prolactin, but fewer effects on more complex central nervous
      system functions, which are likely to involve multiple neurotransmitters.

PMID- 21890592
TI  - Clinical and pathogenic aspects of candidate genes for lithium prophylactic
      efficacy.
AB  - A number of candidate genes for lithium prophylactic efficacy have been proposed,
      some of them being also associated with a predisposition to bipolar illness. The
      aim of the present study was to investigate a possible association between
      polymorphisms of 14 common genes with the quality of prophylactic lithium
      response in patients with bipolar mood disorder, in relation to the putative role
      of these genes in the pathogenesis of this disorder. Some association with
      lithium prophylactic efficacy was found for the polymorphisms of 5HTT, DRD1,
      COMT, BDNF and FYN genes, but not for 5HT2A, 5HT2C, DRD2, DRD3, DRD4, GSK-3,
      NTRK2, GRIN2B and MMP-9. Possible aspects of these genes with regard to the
      mechanism of lithium activity and pathogenesis of bipolar mood disorder are
      discussed.

PMID- 21890593
TI  - Serum levels of BDNF are associated with craving in opiate-dependent patients.
AB  - Preclinical study results suggest that brain-derived neurotrophic factor (BDNF)
      and glial cell line-derived neurotrophic factor (GDNF) are involved in the
      modulation of addictive behaviour. We investigated alterations in serum levels of
      BDNF and GDNF in opiate-dependent patients (28 males) who received
      diacetylmorphine treatment within a structured opiate maintenance programme. BDNF
      (T = 2.735, p = 0.009) serum levels were significantly increased in the opiate
      dependent patients as compared with healthy controls (21 males), whereas GDNF
      serum levels (T = 1.425, p = 0.162) did not differ significantly from GDNF serum
      levels of the healthy controls. BDNF serum levels were significantly associated
      with craving for heroin (measured by the Heroin Craving Questionnaire (r = 0.420,
      p = 0.029) and by the General Craving Scale (r = 0.457, p = 0.016), whereas GDNF
      serum levels were not associated with psychometric dimensions of heroin craving.
      In conclusion, our results show a positive association between BDNF serum levels
      and opiate craving in opiate-dependent patients.

PMID- 21890594
TI  - History of cannabis use is not associated with alterations in striatal dopamine
      D2/D3 receptor availability.
AB  - Cannabis use in adolescence is emerging as a risk factor for the development of
      psychosis. In animal studies, Delta9-tetrahydrocannabinol (THC), the psychoactive
      component of cannabis, modulates striatal dopaminergic neurotransmission.
      Alterations in human striatal dopaminergic function have also been reported both
      in psychosis and in stimulant use. We sought to examine whether striatal dopamine
      D(2)/D(3) receptor availability was altered in volunteers with a history of
      cannabis use using a database of previously acquired [(11)C]-raclopride positron
      emission tomography (PET) scans. Ten [(11)C]-raclopride scans from volunteers
      with a history of cannabis use were compared to ten control scans using a
      functional striatal subdivision region of interest (ROI) analysis. No significant
      differences in either overall striatal BP(ND) values or BP(ND) values in any
      functional striatal subdivision were found between the two groups. There was also
      no correlation between lifetime frequency of cannabis use and BP(ND) values.
      Limbic striatal BP(ND) values were ten percent lower in current nicotine
      cigarette smokers. These findings suggest that, unlike other drugs of abuse, a
      history of cannabis use is not associated with alterations in striatal dopamine
      D(2)/D(3) receptor availability.

PMID- 21890595
TI  - Acute restraint stress enhances hippocampal endocannabinoid function via
      glucocorticoid receptor activation.
AB  - Exposure to behavioural stress normally triggers a complex, multilevel response
      of the hypothalamic-pituitary-adrenal (HPA) axis that helps maintain homeostatic
      balance. Although the endocannabinoid (eCB) system (ECS) is sensitive to chronic
      stress, few studies have directly addressed its response to acute stress. Here we
      show that acute restraint stress enhances eCB-dependent modulation of GABA
      release measured by whole-cell voltage clamp of inhibitory postsynaptic currents
      (IPSCs) in rat hippocampal CA1 pyramidal cells in vitro. Both Ca(2+)-dependent,
      eCB-mediated depolarization-induced suppression of inhibition (DSI), and
      muscarinic cholinergic receptor (mAChR)-mediated eCB mobilization are enhanced
      following acute stress exposure. DSI enhancement is dependent on the activation
      of glucocorticoid receptors (GRs) and is mimicked by both in vivo and in vitro
      corticosterone treatment. This effect does not appear to involve cyclooxygenase-2
      (COX-2), an enzyme that can degrade eCBs; however, treatment of hippocampal
      slices with the L-type calcium (Ca(2+)) channel inhibitor, nifedipine, reverses
      while an agonist of these channels mimics the effect of in vivo stress. Finally,
      we find that acute stress produces a delayed (by 30 min) increase in the
      hippocampal content of 2-arachidonoylglycerol, the eCB responsible for DSI. These
      results support the hypothesis that the ECS is a biochemical effector of
      glucocorticoids in the brain, linking stress with changes in synaptic strength.

PMID- 21890596
TI  - ADHD matures: time for practitioners to do the same?
AB  - Attention deficit and hyperactivity disorder (ADHD) is not restricted to
      children. Abundant evidence from follow-up studies accumulated since the 1970s
      supports the concept of ADHD in adulthood. Genetic research points to a
      heritability of 76%, and neuroimaging studies have reported structural and
      functional brain abnormalities in patients with ADHD. Contrary to popular belief,
      ADHD is not a culturally bound disorder and has been described worldwide. ADHD
      has a cost for society, as adults with this disorder suffer from increased rates
      of unemployment and psychiatric comorbidity, including substance use disorders.
      Studies undertaken in forensic populations describe high rates of ADHD in these
      groups, particularly amongst young offenders. One of the main issues in the
      diagnosis of ADHD in the adult is the fact that most clinicians have not been
      educated to diagnose and treat ADHD. Effective pharmacological treatments for
      ADHD are available and should be prescribed for these patients. The National
      Institute for Health and Clinical Excellence (NICE) and the British Association
      for Psychopharmacology (BAP) guidelines established a benchmark for service
      development required to treat ADHD adequately in the adult population. However,
      the implementation of new services has been slow. More resources are needed to
      effectively assess and treat ADHD in the adult.

PMID- 21890598
TI  - Appeal for funds to support emergency response in Kenya.

PMID- 21890600
TI  - Possible role for MHC I in bleeding calf syndrome.

PMID- 21890597
TI  - Lysophosphatidic acid-induced p21Waf1 expression mediates the cytostatic response
      of breast and ovarian cancer cells to TGFbeta.
AB  - Lysophosphatidic acid (LPA) is a multifunctional intercellular phospholipid
      mediator present in blood and other biological fluids. In cancer cells, LPA
      stimulates expression or activity of inflammatory cytokines, angiogenic factors,
      matrix metalloproteinases, and other oncogenic proteins. In this study, we showed
      that LPA upregulated expression of the cyclin-dependent kinase inhibitor
      p21(Waf1) in TGFbeta-sensitive breast and ovarian cancer cells, but not in
      TGFbeta-resistant ones. We examined the possibility that LPA-induced p21 might
      contribute to the cytostatic response to TGFbeta. In serum-free conditions,
      TGFbeta alone induced p21 expression weakly in TGFbeta-sensitive cells. Serum or
      serum-borne LPA cooperated with TGFbeta to elicit the maximal p21 induction. LPA
      stimulated p21 via LPA(1) and LPA(2) receptors and Erk-dependent activation of
      the CCAAT/enhancer binding protein beta transcription factor independent of p53.
      Loss or gain of p21 expression led to a shift between TGFbeta-sensitive and 
      resistant phenotypes in breast and ovarian cancer cells, indicating that p21 is a
      key determinant of the growth inhibitory activity of TGFbeta. Our results reveal
      a novel cross-talk between LPA and TGFbeta that underlies TGFbeta-sensitive and 
      resistant phenotypes of breast and ovarian cancer cells.

PMID- 21890601
TI  - New pig health and welfare strategy launched by BPEX.

PMID- 21890604
TI  - Finding medicines for horses.

PMID- 21890605
TI  - Investigating the suitability of electronic identification in livestock.

PMID- 21890606
TI  - Where next for veterinary education?

PMID- 21890608
TI  - Idiopathic arterial aneurysm/rupture causing sudden death in dairy cattle.

PMID- 21890609
TI  - Celebrating 150 years of Glasgow vet school.

PMID- 21890610
TI  - Renal function of dairy cows with subclinical ketosis.

PMID- 21890615
TI  - A personalized medicine approach to biologic treatment of rheumatoid arthritis: a
      preliminary treatment algorithm.
AB  - RA is a syndrome consisting of different pathogenetic subsets in which distinct
      molecular mechanisms may drive common final pathways. Recent work has provided
      proof of principle that biomarkers may be identified predictive of the response
      to targeted therapy. Based on new insights, an initial treatment algorithm is
      presented that may be used to guide treatment decisions in patients who have
      failed one TNF inhibitor. Key questions in this algorithm relate to the question
      whether the patient is a primary vs a secondary non-responder to TNF blockade and
      whether the patient is RF and/or anti-citrullinated peptide antibody positive.
      This preliminary algorithm may contribute to more cost-effective treatment of RA,
      and provides the basis for more extensive algorithms when additional data become
      available.

PMID- 21890616
TI  - Calcinosis cutis associated with primary Sjogren's syndrome: strong expression of
      osteonectin and matrix Gla protein.

PMID- 21890618
TI  - Peripheral neuropathy in ANCA-associated vasculitis: outcomes from the European
      Vasculitis Study Group trials.
AB  - OBJECTIVES: To describe the incidence and prevalence of peripheral neuropathy in
      ANCA-associated vasculitis (AAV); to evaluate the correlation of neuropathy with
      other clinical manifestations; and to review the long-term outcome of treated
      neuropathy. METHODS: Presence of neuropathy was determined using items from the
      BVAS and vasculitis damage index (VDI) during 5 years from enrollment into
      clinical trials conducted by the European Vasculitis Study Group (EUVAS).
      RESULTS: Forty (8%) of 506 patients had vasculitic neuropathy at baseline.
      Incidence of vasculitic motor-involving neuropathy was identical between
      microscopic polyangiitis (MPA) [16 (7%) out of 237] and granulomatosis with
      polyangiitis (Wegener's) [19 (7%) out of 269], P = 0.94. Pure sensory neuropathy
      was reported in 5 (2%) out of 269 patients with granulomatosis with polyangiitis,
      but not in patients with MPA, P = 0.065. Vasculitic neuropathy at baseline was
      associated with systemic [odds ratio (OR) = 1.81], cutaneous (OR = 1.29), mucous
      membranes (OR = 1.21) and ENT (OR = 1.14) manifestations of vasculitis (P < 0.05
      for all). There was no association between neuropathy and renal, chest,
      cardiovascular or abdominal vasculitis or with overall mortality. Of the 40
      patients with vasculitic neuropathy at baseline, 35% had complete resolution
      within 6 months. The cumulative prevalence of chronic neuropathy at any time up
      to 5 years was 15% (75 of 506). Chronic neuropathy was associated with older age
      [hazard ratio (HR) = 1.03], higher BVAS (HR = 1.07) and lower baseline creatinine
      (HR = 0.82) (P < 0.01 for all). CONCLUSION: Peripheral neuropathy is an
      occasional accompaniment of AAV that typically remits in concert with non
      neuropathic manifestations, usually involves motor nerves, often produces long
      lasting symptoms and is not associated with life-threatening organ involvement.

PMID- 21890619
TI  - Safety and efficacy of exercise training in patients with an idiopathic
      inflammatory myopathy--a systematic review.
AB  - OBJECTIVE: Idiopathic inflammatory myopathies (IIMs) are a group of rare
      heterogeneous autoimmune skeletal muscle disorders characterized by muscle
      weakness, excessive muscle fatigue and diminished aerobic fitness. Exercise
      training could be one way to prevent or delay the negative effects of the disease
      and the impairments seen in patients with an IIM. The objective was to examine
      whether exercise training is safe and effective in patients with an IIM. METHODS:
      All experimental studies that assessed the safety and/or efficacy of an exercise
      training programme in patients with an IIM except for case studies were reviewed.
      Pre-MEDLINE, MEDLINE and EMBASE database searching was done up to November 2010.
      Information was extracted on the number of participants, characteristics of
      participants, type of intervention, type of outcome measure, type of study
      design, report characteristics, geographical origin and risk of bias within
      studies. The change (percentage and significance) in group mean or median for
      each outcome measure in each study was determined as well. RESULTS: Two
      randomized controlled trials, one non-randomized controlled trial and nine
      uncontrolled trials were included. No studies in children were found. Safety
      measures did not worsen and efficacy measures improved or did not change. Most of
      the included studies had a high selection and/or allocation bias. CONCLUSIONS: In
      conclusion, it appears that exercise training is safe and effective in adult
      patients with active as well as inactive stable IIMs. However, more studies with
      a well-controlled design are needed. In addition, studies in children with an IIM
      are indicated.

PMID- 21890620
TI  - Clinical significance of serum levels of sCD36 in patients with systemic
      sclerosis: preliminary data.
AB  - OBJECTIVE: To evaluate the clinical significance of anti-angiogenic receptor
      cluster of differentiation 36 (CD36) in serum of patients with SSc. METHODS: We
      studied 47 SSc patients (28 with lcSSC and 19 with dcSSC) and 38 age- and gender
      matched healthy controls. Demographic, clinical, autoantibodies and serological
      data were prospectively assessed. Peripheral vascular affection was classified
      into mild, moderate, severe or end-stage based on a vascular severity scale.
      Soluble CD36 (sCD36) serum levels were measured using ELISA. RESULTS: Serum sCD36
      levels were significantly higher in patients with SSc compared with healthy
      controls (P = 0.045). When the patients were divided into clinical subsets, sCD36
      was higher in lcSSc than in healthy controls (P = 0.03). Levels of sCD36 were
      found to be positively correlated with pulmonary artery systolic pressure (PASP)
      and negatively correlated with percentage diffusing lung capacity for carbon
      monoxide (DL(CO)). In the multivariate analysis, 50% of the variation of sCD36
      levels could be explained by elevated PASP (0.000), telangiectasias (0.026) and
      increasing vascular severity (P = 0.003). CONCLUSION: Serum sCD36 levels were
      higher in SSc patients (particularly the limited subset) than in healthy controls
      and were found to be correlated with PASP and vascular severity. We conclude that
      sCD36 may be a marker for elevated PASP and vascular involvement in SSc. To
      confirm our results we propose that larger scale, multicentre studies with longer
      evaluation periods are needed.

PMID- 21890617
TI  - Rheumatoid arthritis and pregnancy: evolution of disease activity and
      pathophysiological considerations for drug use.
AB  - It has long been known that pregnancy and childbirth have a profound effect on
      the disease activity of rheumatic diseases. For clinicians, the management of
      patients with RA wishing to become pregnant involves the challenge of keeping
      disease activity under control and adequately adapting drug therapy during
      pregnancy and post-partum. This article aims to summarize the current evidence on
      the evolution of RA disease activity during and after pregnancy and the use of
      anti-rheumatic drugs around this period. Of recent interest is the potential use
      of anti-TNF compounds in the preconception period and during pregnancy.
      Accumulating experience with anti-TNF therapy in other immune-mediated
      inflammatory diseases, such as Crohn's disease, provides useful insights for the
      use of TNF blockade in pregnant women with RA, or RA patients wishing to become
      pregnant.

PMID- 21890621
TI  - Associations between body mass, radiographic joint damage, adipokines and risk
      factors for bone loss in rheumatoid arthritis.
AB  - OBJECTIVE: To evaluate the association between BMI and radiographic joint damage
      (RJD) in RA. METHODS: van der Heijde-Sharp (vdHS) erosion scores were determined
      in 499 participants with RA, ages 18-85 years, while enrolled in a clinical trial
      of golimumab (GO-BEFORE trial). Subjects were MTX and biologic therapy naive.
      Multivariable logistic regressions determined the odds of prevalent RJD (defined
      as vdHS score >10) according to BMI category. Longitudinal analyses evaluated the
      association between BMI category and progression of vdHS score over 52 weeks.
      Analyses in a subset of 100 participants examined the association between
      adipokines and vdHS scores. RESULTS: At enrolment and 52 weeks, 37.6 and 43.6% of
      participants had RJD. Compared with normal weight, obese subjects had lower odds
      of RJD [0.40 (95% CI 0.22, 0.74); P = 0.003], and underweight subjects had
      greater odds [3.86 (95% CI 1.66, 9.00); P = 0.002] at baseline, adjusted for
      demographic and disease characteristics. The baseline associations between BMI
      category and RJD were greater among participants with multiple risk factors for
      bone loss (female >50 years, smoking, glucocorticoid exposure and vitamin D
      deficiency); test for interaction P = 0.05. Adjustment for adiponectin levels did
      not attenuate the association between BMI and vdHS scores. Baseline BMI and
      change in weight did not independently predict radiographic progression (P >
      0.1). CONCLUSIONS: Higher BMI was independently associated with less RJD and was
      greatest in participants with risk factors for bone loss. Future studies are
      needed to examine the associations between RJD, obesity, weight loss and
      osteoporosis.

PMID- 21890622
TI  - An observational study of tocilizumab and TNF-alpha inhibitor use in a Japanese
      community hospital: different remission rates, similar drug survival and safety.
AB  - OBJECTIVE: To assess the effectiveness, drug survival and safety of tocilizumab
      compared with TNF-alpha inhibitors in clinical practice. METHODS: Patients in the
      Cohort of Arthritis Biologic Users at Kameda Institute (CABUKI) registry who were
      on biologics during July 2003 to October 2010 were included. Remission rates at 6
      months, Kaplan-Meier drug survival estimates and serious adverse event (SAE)
      rates were compared. RESULTS: A total of 247 RA patients were analysed. For first
      line biologic users, the 6-month 28-joint DAS (DAS-28)-ESR remission rates were
      66.7% for tocilizumab vs 25.8% for TNF inhibitors (P < 0.001, Fisher's exact
      test). This advantage disappeared with the application of the newly suggested
      Boolean remission criterion for clinical trials: 0% for tocilizumab vs 8.2% for
      TNF inhibitors (P = 0.367, Fisher's exact test). Tocilizumab users in DAS-28-ESR
      remission had lower mean ESR (3.9  mm/h for tocilizumab vs 7.9  mm/h for TNF
      inhibitors, P = 0.026, t-test) and higher mean swollen joint count (2.6 for
      tocilizumab vs 1.3 for TNF inhibitors, P = 0.036, t-test), thus failing to meet
      the more stringent Boolean criteria. First- and second-line tocilizumab users
      showed similar drug survival and SAE rates compared with TNF inhibitor users.
      CONCLUSION: Tocilizumab had drug survival and safety profiles similar to those of
      TNF inhibitors in this Japanese single-centre registry. Tocilizumab was superior
      to TNF inhibitors when compared at 6 months by DAS-28-ESR remission. However, the
      newly suggested Boolean criteria are more appropriate measures of effectiveness
      as DAS-28-ESR remission by tocilizumab was mainly due to very low ESR in our
      study population.

PMID- 21890623
TI  - Ubiquitin-mediated modulation of the cytoplasmic viral RNA sensor RIG-I.
AB  - RIG-I-like receptors, including RIG-I, MDA5 and LGP2, recognize cytoplasmic viral
      RNA. The RIG-I protein consists of N-terminal CARDs, central RNA helicase and C
      terminal domains. RIG-I activation is regulated by ubiquitination. Three
      ubiquitin ligases target the RIG-I protein. TRIM25 and Riplet ubiquitin ligases
      are positive regulators of RIG-I and deliver the K63-linked polyubiquitin moiety
      to RIG-I CARDs and the C-terminal domain. RNF125, another ubiquitin ligase, is a
      negative regulator of RIG-I and mediates K48-linked polyubiquitination of RIG-I,
      leading to the degradation of the RIG-I protein by proteasomes. The K63-linked
      polyubiquitin chains of RIG-I are removed by a deubiquitin enzyme, CYLD. Thus,
      CYLD is a negative regulator of RIG-I. Furthermore, TRIM25 itself is regulated by
      ubiquitination. HOIP and HOIL proteins are ubiquitin ligases and are also known
      as linear ubiquitin assembly complexes (LUBACs). The TRIM25 protein is
      ubiquitinated by LUBAC and then degraded by proteasomes. The splice variant of
      RIG-I encodes a protein that lacks the first CARD of RIG-I, and the variant RIG-I
      protein is not ubiquitinated by TRIM25. Therefore, ubiquitin is the key regulator
      of the cytoplasmic viral RNA sensor RIG-I.

PMID- 21890624
TI  - Polo-like kinase 1 facilitates loss of Pten tumor suppressor-induced prostate
      cancer formation.
AB  - Loss of the tumor suppressor Pten (phosphatase and tensin homolog deleted on
      chromosome 10) is thought to mediate the majority of prostate cancers, but the
      molecular mechanism remains elusive. In this study, we demonstrate that Pten
      depleted cells suffer from mitotic stress and that nuclear function of Pten, but
      not its phosphatase activity, is required to reverse this stress phenotype.
      Further, depletion of Pten results in elevated expression of Polo-like kinase 1
      (Plk1), a critical regulator of the cell cycle. We show that overexpression of
      Plk1 correlates with genetic inactivation of Pten during prostate neoplasia
      formation. Significantly, we find that elevated Plk1 is critical for Pten
      depleted cells to adapt to mitotic stress for survival and that reintroduction of
      wild-type Pten into Pten-null prostate cancer cells reduces the survival
      dependence on Plk1. We further show that Plk1 confers the tumorigenic competence
      of Pten-deleted prostate cancer cells in a mouse xenograft model. These findings
      identify a role of Plk1 in facilitating loss of Pten-induced prostate cancer
      formation, which suggests that Plk1 might be a promising target for prostate
      cancer patients with inactivating Pten mutations.

PMID- 21890625
TI  - Tbx20 transcription factor is a downstream mediator for bone morphogenetic
      protein-10 in regulating cardiac ventricular wall development and function.
AB  - Bone morphogenetic protein 10 (BMP10) belongs to the TGFbeta-superfamily.
      Previously, we had demonstrated that BMP10 is a key regulator for ventricular
      chamber formation, growth, and maturation. Ablation of BMP10 leads to hypoplastic
      ventricular wall formation, and elevated levels of BMP10 are associated with
      abnormal ventricular trabeculation/compaction and wall maturation. However, the
      molecular mechanism(s) by which BMP10 regulates ventricle wall growth and
      maturation is still largely unknown. In this study, we sought to identify the
      specific transcriptional network that is potentially mediated by BMP10. We
      analyzed and compared the gene expression profiles between alpha-myosin heavy
      chain (alphaMHC)-BMP10 transgenic hearts and nontransgenic littermate controls
      using Affymetrix mouse exon arrays. T-box 20 (Tbx20), a cardiac transcription
      factor, was significantly up-regulated in alphaMHC-BMP10 transgenic hearts, which
      was validated by quantitative RT-PCR and in situ hybridization. Ablation of BMP10
      reduced Tbx20 expression specifically in the BMP10-expressing region of the
      developing ventricle. In vitro promoter analysis demonstrated that BMP10 was able
      to induce Tbx20 promoter activity through a conserved Smad binding site in the
      Tbx20 promoter proximal region. Furthermore, overexpression of Tbx20 in
      myocardium led to dilated cardiomyopathy that exhibited ventricular
      hypertrabeculation and an abnormal muscular septum, which phenocopied genetically
      modified mice with elevated BMP10 levels. Taken together, our findings
      demonstrate that the BMP10-Tbx20 signaling cascade is important for ventricular
      wall development and maturation.

PMID- 21890626
TI  - Charcot-Marie-Tooth-related gene GDAP1 complements cell cycle delay at G2/M phase
      in Saccharomyces cerevisiae fis1 gene-defective cells.
AB  - Mutations in the GDAP1 gene are responsible of the Charcot-Marie-Tooth CMT4A,
      ARCMT2K, and CMT2K variants. GDAP1 is a mitochondrial outer membrane protein that
      has been related to the fission pathway of the mitochondrial network dynamics. As
      mitochondrial dynamics is a conserved process, we reasoned that expressing GDAP1
      in Saccharomyces cerevisiae strains defective for genes involved in mitochondrial
      fission or fusion could increase our knowledge of GDAP1 function. We discovered a
      consistent relation between Fis1p and the cell cycle because fis1Delta cells
      showed G(2)/M delay during cell cycle progression. The fis1Delta phenotype, which
      includes cell cycle delay, was fully rescued by GDAP1. By contrast, clinical
      missense mutations rescued the fis1Delta phenotype except for the cell cycle
      delay. In addition, both Fis1p and human GDAP1 interacted with beta-tubulins
      Tub2p and TUBB, respectively. A defect in the fis1 gene may induce abnormal
      location of mitochondria during budding mitosis, causing the cell cycle delay at
      G(2)/M due to its anomalous interaction with microtubules from the mitotic
      spindle. In the case of neurons harboring defects in GDAP1, the interaction
      between mitochondria and the microtubule cytoskeleton would be altered, which
      might affect mitochondrial axonal transport and movement within the cell and may
      explain the pathophysiology of the GDAP1-related Charcot-Marie-Tooth disease.

PMID- 21890627
TI  - MYPT1 protein isoforms are differentially phosphorylated by protein kinase G.
AB  - Smooth muscle relaxation in response to NO signaling is due, in part, to a Ca(2+)
      independent activation of myosin light chain (MLC) phosphatase by protein kinase
      G Ialpha (PKGIalpha). MLC phosphatase is a trimeric complex of a 20-kDa subunit,
      a 38-kDa catalytic subunit, and a 110-133-kDa myosin-targeting subunit (MYPT1).
      Alternative mRNA splicing produces four MYPT1 isoforms, differing by the presence
      or absence of a central insert and leucine zipper (LZ). The LZ domain of MYPT1
      has been shown to be important for PKGIalpha-mediated activation of MLC
      phosphatase activity, and changes in LZ+ MYPT1 isoform expression result in
      changes in the sensitivity of smooth muscle to NO-mediated relaxation.
      Furthermore, PKGIalpha has been demonstrated to phosphorylate Ser-694 of MYPT1,
      but phosphorylation at this site does not always accompany cGMP-mediated smooth
      muscle relaxation. This study was designed to determine whether MYPT1 isoforms
      are differentially phosphorylated by PKGIalpha. The results demonstrate that
      purified LZ+ MYPT1 fragments are rapidly phosphorylated by PKGIalpha at Ser-667
      and Ser-694, whereas fragments lacking the LZ domain are poor PKGIalpha
      substrates. Mutation of Ser-667 and Ser-694 to Ala and/or Asp showed that Ser-667
      phosphorylation is more rapid than Ser-694 phosphorylation, suggesting that Ser
      667 may play an important role in the activation of MLC phosphatase. These
      results demonstrate that MYPT1 isoform expression is important for determining
      the heterogeneous response of vascular beds to NO and NO-based vasodilators,
      thereby playing a central role in the regulation of vascular tone in health and
      disease.

PMID- 21890628
TI  - The regulator of calcineurin 1 (RCAN1/DSCR1) activates the cAMP response element
      binding protein (CREB) pathway.
AB  - cAMP response element-binding protein (CREB) is one of the best known
      transcription factors in the development and function of the nervous system. In
      this report, we found that the regulator of calcineurin 1 (RCAN1), which is
      overexpressed in the brain of patients with Down syndrome, increased the
      phosphorylation of CREB and cAMP response element-mediated gene transcription in
      response to the activation of the intracellular cAMP pathway. Furthermore, we
      found that the increased activation of CREB signaling by RCAN1 depended on the
      ability of RCAN1 to inhibit calcineurin activity. Our data provide the first
      evidence that RCAN1 acts as an important regulatory component in the control of
      CREB signaling.

PMID- 21890629
TI  - Extra-long Galphas variant XLalphas protein escapes activation-induced
      subcellular redistribution and is able to provide sustained signaling.
AB  - Murine models indicate that Galphas and its extra-long variant XLalphas, both of
      which are derived from GNAS, markedly differ regarding their cellular actions,
      but these differences are unknown. Here we investigated activation-induced
      trafficking of Galphas and XLalphas, using immunofluorescence microscopy, cell
      fractionation, and total internal reflection fluorescence microscopy. In
      transfected cells, XLalphas remained localized to the plasma membrane, whereas
      Galphas redistributed to the cytosol after activation by GTPase-inhibiting
      mutations, cholera toxin treatment, or G protein-coupled receptor agonists
      (isoproterenol or parathyroid hormone (PTH)(1-34)). Cholera toxin treatment or
      agonist (isoproterenol or pituitary adenylate cyclase activating peptide-27)
      stimulation of PC12 cells expressing Galphas and XLalphas endogenously led to an
      increased abundance of Galphas, but not XLalphas, in the soluble fraction.
      Mutational analyses revealed two conserved cysteines and the highly charged
      domain as being critically involved in the plasma membrane anchoring of XLalphas.
      The cAMP response induced by M-PTH(1-14), a parathyroid hormone analog,
      terminated quickly in HEK293 cells stably expressing the type 1 PTH/PTH-related
      peptide receptor, whereas the response remained maximal for at least 6 min in
      cells that co-expressed the PTH receptor and XLalphas. Although isoproterenol
      induced cAMP response was not prolonged by XLalphas expression, a GTPase
      deficient XLalphas mutant found in certain tumors and patients with fibrous
      dysplasia of bone and McCune-Albright syndrome generated more basal cAMP
      accumulation in HEK293 cells and caused more severe impairment of osteoblastic
      differentiation of MC3T3-E1 cells than the cognate Galphas mutant (gsp oncogene).
      Thus, activated XLalphas and Galphas traffic differently, and this may form the
      basis for the differences in their cellular actions.

PMID- 21890630
TI  - Allosteric communication in cysteinyl tRNA synthetase: a network of direct and
      indirect readout.
AB  - Protein structure networks are constructed for the identification of long-range
      signaling pathways in cysteinyl tRNA synthetase (CysRS). Molecular dynamics
      simulation trajectory of CysRS-ligand complexes were used to determine
      conformational ensembles in order to gain insight into the allosteric signaling
      paths. Communication paths between the anticodon binding region and the
      aminoacylation region have been identified. Extensive interaction between the
      helix bundle domain and the anticodon binding domain, resulting in structural
      rigidity in the presence of tRNA, has been detected. Based on the predicted
      model, six residues along the communication paths have been examined by mutations
      (single and double) and shown to mediate a coordinated coupling between anticodon
      recognition and activation of amino acid at the active site. This study on CysRS
      clearly shows that specific key residues, which are involved in communication
      between distal sites in allosteric proteins but may be elusive in direct
      structure analysis, can be identified from dynamics of protein structure
      networks.

PMID- 21890631
TI  - AKAP220 protein organizes signaling elements that impact cell migration.
AB  - Cell movement requires the coordinated reception, integration, and processing of
      intracellular signals. We have discovered that the protein kinase A anchoring
      protein AKAP220 interacts with the cytoskeletal scaffolding protein IQGAP1 to
      influence cell motility. AKAP220/IQGAP1 networks receive and integrate calcium
      and cAMP second messenger signals and position signaling enzymes near their
      intended substrates at leading edges of migrating cells. IQGAP1 supports
      calcium/calmodulin-dependent association of factors that modulate microtubule
      dynamics. AKAP220 suppresses GSK-3beta and positions this kinase to allow
      recruitment of the plus-end microtubule tracking protein CLASP2. Gene silencing
      of AKAP220 alters the rate of microtubule polymerization and the lateral tracking
      of growing microtubules and retards cell migration in metastatic human cancer
      cells. This reveals an unappreciated role for this anchored kinase/microtubule
      effector protein network in the propagation of cell motility.

PMID- 21890632
TI  - Consensus substrate sequence for protein-tyrosine phosphatase receptor type Z.
AB  - Protein-tyrosine phosphatase receptor type Z (Ptprz) has multiple substrate
      proteins, including G protein-coupled receptor kinase-interactor 1 (Git1),
      membrane-associated guanylate kinase, WW and PDZ domain-containing 1 (Magi1), and
      GTPase-activating protein for Rho GTPase (p190RhoGAP). We have identified a
      dephosphorylation site at Tyr-1105 of p190RhoGAP; however, the structural
      determinants employed for substrate recognition of Ptprz have not been fully
      defined. In the present study, we revealed that Ptprz selectively
      dephosphorylates Git1 at Tyr-554, and Magi1 at Tyr-373 and Tyr-858 by in vitro
      and cell-based assays. Of note, the dephosphorylation of the Magi1 Tyr-858 site
      required PDZ domain-mediated interaction between Magi1 and Ptprz in the cellular
      context. Alignment of the primary sequences surrounding the target
      phosphotyrosine residue in these three substrates showed considerable similarity,
      suggesting a consensus motif for recognition by Ptprz. We then estimated the
      contribution of surrounding individual amino acid side chains to the catalytic
      efficiency by using fluorescent peptides based on the Git1 Tyr-554 sequence in
      vitro. The typical substrate motif for the catalytic domain of Ptprz was deduced
      to be Glu/Asp-Glu/Asp-Glu/Asp-Xaa-Ile/Val-Tyr(P)-Xaa (Xaa is not an acidic
      residue). Intriguingly, a G854D substitution of the Magi1 Tyr-858 site matching
      better to the motif sequence turned this site to be susceptible to
      dephosphorylation by Ptprz independent of the PDZ domain-mediated interaction in
      cells. Furthermore, we found by database screening that the substrate motif is
      present in several proteins, including paxillin at Tyr-118, its major
      phosphorylation site. Expectedly, we verified that Ptprz efficiently
      dephosphorylates paxillin at this site in cells. Our study thus provides key
      insights into the molecular basis for the substrate recognition of Ptprz.

PMID- 21890633
TI  - New mode of action for a knottin protein bioinsecticide: pea albumin 1 subunit b
      (PA1b) is the first peptidic inhibitor of V-ATPase.
AB  - PA1b (for pea albumin 1 subunit b) is a plant bioinsecticide lethal to several
      pests that are important in agriculture or human health. PA1b belongs to the
      inhibitory cystine knot family or knottin family. Originating from a plant (the
      garden pea) commonly eaten by humans without any known toxic or allergic effects,
      PA1b is a candidate for transgenic applications and is one of the most promising
      biopesticides for pest control. Using whole-cell patch-clamp techniques on Sf9
      PA1b-sensitive lepidopteran insect cells, we discovered that PA1b reversibly
      blocked ramp membrane currents in a dose-dependent manner (EC(50) = 0.52 MUM).
      PA1b had the same effect as bafilomycin, a specific inhibitor of the vacuolar
      proton pump (V-type H(+)-ATPase), and the PA1b-sensitive current depended on the
      internal proton concentration. Biochemical assays on purified V-ATPase from the
      lepidopteran model Manduca sexta showed that PA1b inhibited the V(1)V(0)-type
      H(+)-ATPase holoenzyme activity (IC(50) ~ 70 nM) by interacting with the membrane
      bound V(0) part of the V-ATPase. V-ATPase is a complex protein that has been
      studied increasingly because of its numerous physiological roles. In the midgut
      of insects, V-ATPase activity is essential for energizing nutrient absorption,
      and the results reported in this work explain the entomotoxic properties of PA1b.
      Targeting V-ATPase is a promising means of combating insect pests, and PA1b
      represents the first peptidic V-ATPase inhibitor. The search for V-ATPase
      inhibitors is currently of great importance because it has been demonstrated that
      V-ATPase plays a role in so many physiological processes.

PMID- 21890634
TI  - Genomic analyses of the RNA-binding protein Hu antigen R (HuR) identify a complex
      network of target genes and novel characteristics of its binding sites.
AB  - The ubiquitously expressed RNA-binding protein Hu antigen R (HuR) or ELAVL1 is
      implicated in a variety of biological processes as well as being linked with a
      number of diseases, including cancer. Despite a great deal of prior investigation
      into HuR, there is still much to learn about its function. We take an important
      step in this direction by conducting cross-linking and immunoprecipitation and
      RNA sequencing experiments followed by an extensive computational analysis to
      determine the characteristics of the HuR binding site and impact on the
      transcriptome. We reveal that HuR targets predominantly uracil-rich single
      stranded stretches of varying size, with a strong conservation of structure and
      sequence composition. Despite the fact that HuR sites are observed in intronic
      regions, our data do not support a role for HuR in regulating splicing. HuR sites
      in 3'-UTRs overlap extensively with predicted microRNA target sites, suggesting
      interplay between the functions of HuR and microRNAs. Network analysis showed
      that identified targets containing HuR binding sites in the 3' UTR are highly
      interconnected.

PMID- 21890635
TI  - Role of MbtH-like proteins in the adenylation of tyrosine during aminocoumarin
      and vancomycin biosynthesis.
AB  - MbtH-like proteins consist of ~70 amino acids and are encoded in the biosynthetic
      gene clusters of non-ribosomally formed peptides and other secondary metabolites
      derived from amino acids. Recently, several MbtH-like proteins have been shown to
      be required for the adenylation of amino acid in non-ribosomal peptide synthesis.
      We now investigated the role of MbtH-like proteins in the biosynthesis of the
      aminocoumarin antibiotics novobiocin, clorobiocin, and simocyclinone D8 and of
      the glycopeptide antibiotic vancomycin. The tyrosine-adenylating enzymes CloH,
      SimH, and Pcza361.18, involved in the biosynthesis of clorobiocin, simocyclinone
      D8, and vancomycin, respectively, required the presence of MbtH-like proteins in
      a 1:1 molar ratio, forming heterotetrameric complexes. In contrast, NovH,
      involved in novobiocin biosynthesis, showed activity in the absence of MbtH-like
      proteins. Comparison of the active centers of CloH and NovH showed only one amino
      acid to be different, i.e. Leu-383 versus Met-383. Mutation of this amino acid in
      CloH (L383M) indeed led to MbtH-independent adenylating activity. All
      investigated tyrosine-adenylating enzymes exhibited remarkable promiscuity for
      MbtH-like proteins from different pathways and organisms. YbdZ, the MbtH-like
      protein from the expression host Escherichia coli, was found to bind to
      adenylating enzymes during expression and to influence their biochemical
      properties markedly. Therefore, the use of ybdZ-deficient expression hosts is
      important in biochemical studies of adenylating enzymes.

PMID- 21890637
TI  - Ubiquitin-specific cysteine protease 2a (USP2a) regulates the stability of Aurora
      A.
AB  - The ubiquitin/proteasome pathway plays critical roles in virtually all aspects of
      cell biology. Enzymes of the ubiquitin pathway add (ligases) or remove
      (deubiquitinases) ubiquitin tags to or from their target proteins in a selective
      fashion. USP2a is a member of a subfamily of deubiquitinases, called ubiquitin
      specific cysteine proteases (USPs). Although USP2a has been reported to be a bona
      fide oncogene that regulates the stability of MDM2, MDMX, and FAS, it is likely
      that there are other unidentified substrates for USP2a. In this study, we show
      that USP2a mediates mitotic progression by regulating the stability of Aurora-A.
      Through cell-based screening of a USP siRNA library, we discovered that knockdown
      of USP2a reduced the protein levels of Aurora-A. USP2a interacts with Aurora-A
      directly in vitro and in vivo. In addition, Aurora-A is a substrate for USP2a in
      vitro and in vivo. Our study provides a novel mechanism for the role of USP2a in
      mediating the stability of Aurora-A.

PMID- 21890636
TI  - Alternative splicing modulates inactivation of type 1 voltage-gated sodium
      channels by toggling an amino acid in the first S3-S4 linker.
AB  - Voltage-gated sodium channels underlie the upstroke of action potentials and are
      fundamental to neuronal excitability. Small changes in the behavior of these
      channels are sufficient to change neuronal firing and trigger seizures. These
      channels are subject to highly conserved alternative splicing, affecting the
      short linker between the third transmembrane segment (S3) and the voltage sensor
      (S4) in their first domain. The biophysical consequences of this alternative
      splicing are incompletely understood. Here we focus on type 1 sodium channels
      (Nav1.1) that are implicated in human epilepsy. We show that the functional
      consequences of alternative splicing are highly sensitive to recording
      conditions, including the identity of the major intracellular anion and the
      recording temperature. In particular, the inactivation kinetics of channels
      containing the alternate exon 5N are more sensitive to intracellular fluoride
      ions and to changing temperature than channels containing exon 5A. Moreover,
      Nav1.1 channels containing exon 5N recover from inactivation more rapidly at
      physiological temperatures. Three amino acids differ between exons 5A and 5N.
      However, the changes in sensitivity and stability of inactivation were reproduced
      by a single conserved change from aspartate to asparagine in channels containing
      exon 5A, which was sufficient to make them behave like channels containing the
      complete exon 5N sequence. These data suggest that splicing at this site can
      modify the inactivation of sodium channels and reveal a possible interaction
      between splicing and anti-epileptic drugs that stabilize sodium channel
      inactivation.

PMID- 21890638
TI  - Expression patterns and function of chromatin protein HMGB2 during mesenchymal
      stem cell differentiation.
AB  - The superficial zone (SZ) of articular cartilage is critical in maintaining
      tissue function and homeostasis and represents the site of the earliest changes
      in osteoarthritis (OA). The expression of chromatin protein HMGB2 is restricted
      to the SZ, which contains cells expressing mesenchymal stem cell (MSC) markers.
      Age-related loss of HMGB2 and gene deletion are associated with reduced SZ
      cellularity and early onset OA. This study addressed HMGB2 expression patterns in
      MSC and its role during differentiation. HMGB2 was detected at higher levels in
      human MSC as compared with human articular chondrocytes, and its expression
      declined during chondrogenic differentiation of MSC. Lentiviral HMGB2
      transduction of MSC suppressed chondrogenesis as reflected by an inhibition of
      Col2a1 and Col10a1 expression. Conversely, in bone marrow MSC from Hmgb2(-/-)
      mice, Col10a1 was more strongly expressed than in wild-type MSC. This is
      consistent with in vivo results from mouse growth plates showing that Hmgb2 is
      expressed in proliferating and prehypertrophic zones but not in hypertrophic
      cartilage where Col10a1 is strongly expressed. Osteogenesis was also accelerated
      in Hmgb2(-/-) MSC. The expression of Runx2, which plays a major role in late
      stage chondrocyte differentiation, was enhanced in Hmgb2(-/-) MSC, and HMGB2
      negatively regulated the stimulatory effect of Wnt/beta-catenin signaling on the
      Runx2 proximal promoter. These results demonstrate that HMGB2 expression is
      inversely correlated with the differentiation status of MSC and that HMGB2
      suppresses chondrogenic differentiation. The age-related loss of HMGB2 in
      articular cartilage may represent a mechanism responsible for the decline in
      adult cartilage stem cell populations.

PMID- 21890640
TI  - Gamete formation resets the aging clock in yeast.
AB  - Gametogenesis is a process whereby a germ cell differentiates into haploid
      gametes. We found that, in budding yeast, replicatively aged cells remove age
      induced cellular damage during gametogenesis. Importantly, gametes of aged cells
      have the same replicative potential as those derived from young cells, indicating
      that life span resets during gametogenesis. Here, we explore the potential
      mechanisms responsible for gametogenesis-induced rejuvenation and discuss
      putative analogous mechanisms in higher eukaryotes.

PMID- 21890642
TI  - Regulated histone methyltransferase and demethylase complexes in the control of
      genes by nuclear receptors.
AB  - Liganded nuclear receptors (NRs) are DNA-binding transcription factors that
      control the transcription of target genes. Such NRs exert their transcriptional
      functions via ligand binding-induced interactions with a number of coregulator
      complexes to reorganize chromatin state. Intensive investigation of NR
      coregulator complexes has revealed that, besides histone acetylation, histone
      methylation is critical for ligand-dependent transcriptional controls by NRs. Our
      recent biochemical screening for NR coregulator complexes showed that the
      enzymatic activities of these histone methylation/demethylation complexes are
      under the control of posttranslational modifications (PTMs) of their catalytic
      subunit. Characterization of such regulated complexes has established the concept
      that transcriptional coregulator complexes sense and decode cellular signals at
      the molecular level. In this symposium review, we will illustrate our recent
      findings regarding PTM-based regulation of NR transcriptional control and discuss
      how these findings are applicable to the diverse roles of NR coregulators in
      interpreting regulatory signals into proper gene regulation.

PMID- 21890641
TI  - Circadian clocks in fuel harvesting and energy homeostasis.
AB  - Circadian systems have evolved in plants, eubacteria, neurospora, and the metazoa
      as a mechanism to optimize energy acquisition and storage in synchrony with the
      rotation of the Earth on its axis. In plants, circadian clocks drive the
      expression of genes involved in oxygenic photosynthesis during the light and
      nitrogen fixation during the dark, repeating this cycle each day. In mammals, the
      core clock in the suprachiasmatic nucleus (SCN) functions to entrain extra-SCN
      and peripheral clocks to the light cycle, including regions central to energy
      homeostasis and sleep, as well as peripheral tissues involved in glucose and
      lipid metabolism. Tissue-specific gene targeting has shown a primary role of
      clock genes in endocrine pancreas insulin secretion, indicating that local clocks
      play a cell-autonomous role in organismal homeostasis. A present focus is to
      dissect the consequences of clock disruption on modulation of nuclear hormone
      receptor signaling and on posttranscriptional regulation of intermediary
      metabolism. Experimental genetic studies have pointed toward extensive interplay
      between circadian and metabolic systems and offer a means to dissect the impact
      of local tissue molecular clocks on fuel utilization across the sleep-wake cycle.

PMID- 21890643
TI  - The CXCR4 antagonist plerixafor corrects panleukopenia in patients with WHIM
      syndrome.
AB  - WHIM syndrome is a rare congenital immunodeficiency disorder characterized by
      warts, hypogammaglobulinemia, infections, and myelokathexis (neutropenia because
      of impaired egress from the BM); most patients also have severe panleukopenia.
      Because WHIM syndrome is caused by mutations in the chemokine receptor CXCR4 that
      result in increased agonist-dependent signaling, we hypothesized that the CXCR4
      antagonist plerixafor (Mozobil [Genyzme Corporation], AMD3100), might be an
      effective treatment. To test this, we enrolled 3 unrelated adult patients with
      the most common WHIM mutation, CXCR4(R334X), in a phase 1 dose-escalation study.
      Plerixafor increased absolute lymphocyte, monocyte, and neutrophil counts in
      blood to normal without significant side effects in all 3 patients. Peak
      responses occurred at 3-12 hours after injection and waned by 24 hours after
      injection which tracked the drug's pharmacokinetics. All 3 cell types increased
      in a dose-dependent manner with the rank order of responsiveness absolute
      lymphocyte > monocyte > neutrophil. These data provide the first pharmacologic
      evidence that panleukopenia in WHIM syndrome is caused by CXCL12-CXCR4 signaling
      dependent leukocyte sequestration, and support continued study of plerixafor as
      mechanism-based therapy in this disease. This study is registered at
      http://www.clinicaltrials.gov as NCT00967785.

PMID- 21890644
TI  - Heparin and warfarin anticoagulation intensity as predictors of recurrence after
      deep vein thrombosis or pulmonary embolism: a population-based cohort study.
AB  - To test recommended anticoagulation measures as predictors of 180-day venous
      thromboembolism (VTE) recurrence, we identified all Olmsted County, MN residents
      with incident VTE over the 14-year period of 1984-1997, and followed each case (N
      = 1166) forward in time for VTE recurrence. We tested the activated partial
      thromboplastin time (APTT), international normalized ratio (INR), and other
      measures of heparin and warfarin anticoagulation as predictors of VTE recurrence
      while controlling for baseline and time-dependent characteristics using Cox
      proportional hazards modeling. Overall, 1026 (88%) and 989 (85%) patients
      received heparin and warfarin, respectively, and 85 (8%) developed VTE
      recurrence. In multivariable analyses, increasing proportions of time on heparin
      with an APTT >= 0.2 anti-X(a) U/mL and on warfarin with an INR >= 2.0 were
      associated with significant reductions in VTE recurrence, while the hazard with
      active cancer was significantly increased. Time from VTE onset to heparin start,
      duration of overlapping heparin and warfarin, and inferior vena cava (IVC) filter
      placement were not independent predictors of recurrence. At a heparin dose >= 30
      000 U/d, the median proportion of time with an APTT >= 0.2 anti-X(a) U/mL was
      92%, suggesting that routine APTT monitoring and heparin dose adjustment may be
      unnecessary. In summary, lower-intensity heparin and standard-intensity warfarin
      anticoagulation are effective in preventing VTE recurrence.

PMID- 21890645
TI  - Arabidopsis TERMINAL FLOWER1 is involved in the regulation of flowering time and
      inflorescence development through transcriptional repression.
AB  - TERMINAL FLOWER1 (TFL1) is a key regulator of flowering time and the development
      of the inflorescence meristem in Arabidopsis thaliana. TFL1 and FLOWERING LOCUS T
      (FT) have highly conserved amino acid sequences but opposite functions. For
      example, FT promotes flowering and TFL1 represses it; FT-overexpressing plants
      and TFL1 loss-of-function mutants have a similar phenotype production of terminal
      flowers in the shoot apex. FT is believed to function in a transcriptional
      activator complex by interacting with FD. Here, we demonstrate that TFL1 is
      involved in the transcriptional repression of genes that are activated by FT. We
      analyzed transgenic plants overexpressing TFL1 fused to a transcriptional
      repressor domain (TFL1-SRDX) or an activator domain (TFL1-VP16). Plants carrying
      35S:TFL1-SRDX showed delayed flowering similar to 35S:TFL1 plants, and plants
      carrying 35S:TFL1-VP16 showed an early flowering phenotype and produced terminal
      flowers. Furthermore, the tfl1 and 35S:TFL1-VP16 plant phenotypes were strongly
      suppressed by the fd mutation, and TFL1 interacted with FD in the cell nucleus,
      as shown by bimolecular fluorescence complementation experiments. We conclude
      that TFL1 negatively modulates the FD-dependent transcription of target genes to
      fine-tune flowering time and the development of the inflorescence meristem.

PMID- 21890646
TI  - TERMINAL FLOWER1 acts in transcriptional repression.

PMID- 21890647
TI  - Integrative annotation of human large intergenic noncoding RNAs reveals global
      properties and specific subclasses.
AB  - Large intergenic noncoding RNAs (lincRNAs) are emerging as key regulators of
      diverse cellular processes. Determining the function of individual lincRNAs
      remains a challenge. Recent advances in RNA sequencing (RNA-seq) and
      computational methods allow for an unprecedented analysis of such transcripts.
      Here, we present an integrative approach to define a reference catalog of >8000
      human lincRNAs. Our catalog unifies previously existing annotation sources with
      transcripts we assembled from RNA-seq data collected from ~4 billion RNA-seq
      reads across 24 tissues and cell types. We characterize each lincRNA by a
      panorama of >30 properties, including sequence, structural, transcriptional, and
      orthology features. We found that lincRNA expression is strikingly tissue
      specific compared with coding genes, and that lincRNAs are typically coexpressed
      with their neighboring genes, albeit to an extent similar to that of pairs of
      neighboring protein-coding genes. We distinguish an additional subset of
      transcripts that have high evolutionary conservation but may include short ORFs
      and may serve as either lincRNAs or small peptides. Our integrated,
      comprehensive, yet conservative reference catalog of human lincRNAs reveals the
      global properties of lincRNAs and will facilitate experimental studies and
      further functional classification of these genes.

PMID- 21890648
TI  - Cooperation between both Wnt/{beta}-catenin and PTEN/PI3K/Akt signaling promotes
      primitive hematopoietic stem cell self-renewal and expansion.
AB  - Although self-renewal is the central property of stem cells, the underlying
      mechanism remains inadequately defined. Using a hematopoietic stem and progenitor
      cell (HSPC)-specific conditional induction line, we generated a compound genetic
      model bearing both Pten deletion and beta-catenin activation. These double mutant
      mice exhibit a novel phenotype, including expansion of phenotypic long-term
      hematopoietic stem cells (LT-HSCs) without extensive differentiation.
      Unexpectedly, constitutive activation of beta-catenin alone results in apoptosis
      of HSCs. However, together, the Wnt/beta-catenin and PTEN/PI3k/Akt pathways
      interact to drive phenotypic LT-HSC expansion by inducing proliferation while
      simultaneously inhibiting apoptosis and blocking differentiation, demonstrating
      the necessity of complementary cooperation between the two pathways in promoting
      self-renewal. Mechanistically, beta-catenin activation reduces multiple
      differentiation-inducing transcription factors, blocking differentiation
      partially through up-regulation of Inhibitor of differentiation 2 (Id2). In
      double mutants, loss of Pten enhances the HSC anti-apoptotic factor Mcl-1. All of
      these contribute in a complementary way to HSC self-renewal and expansion. While
      permanent, genetic alteration of both pathways in double mutant mice leads to
      expansion of phenotypic HSCs, these HSCs cannot function due to blocked
      differentiation. We developed a pharmacological approach to expand normal,
      functional HSCs in culture using factors that reversibly activate both Wnt/beta
      catenin and PI3K/Akt signaling simultaneously. We show for the first time that
      activation of either single pathway is insufficient to expand primitive HSCs, but
      in combination, both pathways drive self-renewal and expansion of HSCs with long
      term functional capacity.

PMID- 21890650
TI  - Pheochromocytoma and pregnancy: a deceptive connection.
AB  - A pheochromocytoma in a pregnant patient is one of the most threatening medical
      conditions for mother, fetus, and physician. Although extraordinarily rare with a
      frequency of 0.002% of all pregnancies, this tumor is notorious for its
      devastating consequences. As in non-pregnant patients, the signs and symptoms are
      quite variable but not specific, with hypertension being one of the most
      prominent signs. Confusion with the much more prevalent forms of pregnancy
      related hypertension is the main cause of overlooking the diagnosis. If
      undiagnosed, maternal and fetal mortality is around 50%. Conversely, early
      detection and proper treatment during pregnancy decrease the maternal and fetal
      mortality to <5 and 15% respectively. For the biochemical diagnosis, plasma or
      urinary metanephrines are the tests of first choice since they have a nearly
      maximal negative predictive value. For reliable localization, only magnetic
      resonance imaging is suitable, with a sensitivity of more than 90%. When the
      tumor is diagnosed in the first 24 weeks of gestation, it should be removed by
      laparoscopic adrenalectomy after 10-14 days of medical preparation with the same
      drugs as in non-pregnant patients. If the tumor is diagnosed in the third
      trimester, the patient should be managed until the fetus is viable using the same
      drug regimen as for regular surgical preparation. Cesarean section with tumor
      removal in the same session or at a later stage is then preferred since vaginal
      delivery is possibly associated with higher mortality. Despite all technical
      diagnostic and therapeutic progress over the last decades, the key factor for
      further reduction of maternal and fetal mortality is early awareness and
      recognition of the potential presence of a pheochromocytoma in a pregnant patient
      with hypertension.

PMID- 21890649
TI  - Identification of enzyme activity quantitative trait loci in a Solanum
      lycopersicum x Solanum pennellii introgression line population.
AB  - Activities of 28 enzymes from central carbon metabolism were measured in pericarp
      tissue of ripe tomato fruits from field trials with an introgression line (IL)
      population generated by introgressing segments of the genome of the wild relative
      Solanum pennellii (LA0716) into the modern tomato cultivar Solanum lycopersicum
      M82. Enzyme activities were determined using a robotized platform in optimized
      conditions, where the activities largely reflect the level of the corresponding
      proteins. Two experiments were analyzed from years with markedly different
      climate conditions. A total of 27 quantitative trait loci were shared in both
      experiments. Most resulted in increased enzyme activity when a portion of the S.
      lycopersicum genome was substituted with the corresponding portion of the genome
      of S. pennellii. This reflects the change in activity between the two parental
      genotypes. The mode of inheritance was studied in a heterozygote IL population. A
      similar proportion of quantitative trait loci (approximately 30%) showed
      additive, recessive, and dominant modes of inheritance, with only 5% showing
      overdominance. Comparison with the location of putative genes for the
      corresponding proteins indicates a large role of trans-regulatory mechanisms.
      These results point to the genetic control of individual enzyme activities being
      under the control of a complex program that is dominated by a network of trans
      acting genes.

PMID- 21890651
TI  - Approach to the patient with advanced differentiated thyroid cancer.
AB  - Patients with advanced thyroid cancer may benefit from l-thyroxine treatment at
      doses that suppress serum TSH level, local treatment interventions, and
      radioiodine therapy. In those patients who are refractory to radioiodine therapy
      and in whom progressive disease has been documented, the efficacy of cytotoxic
      chemotherapy is poor. Encouraging results have been obtained with the use of
      kinase inhibitors that should be offered as first-line treatment, preferably in
      the context of a prospective trial.

PMID- 21890652
TI  - Family history of diabetes and distribution of class II HLA genotypes in children
      with newly diagnosed type 1 diabetes: effect on diabetic ketoacidosis.
AB  - OBJECTIVE: Our purpose was to assess whether family history of diabetes or the
      HLA-DR-DQ genotype of the index case was associated with the frequency of
      diabetic ketoacidosis (DKA) at diagnosis of childhood type 1 diabetes. PATIENTS
      AND METHODS: The study cohort comprised 1518 children aged <15 years and
      diagnosed with type 1 diabetes in Finland in 2002-2005. Family history of type 1
      and type 2 diabetes among first-degree relatives (FDRs) and grandparents was
      assessed at diagnosis. HLA-DR-DQ genotypes were analysed using time-resolved
      fluorometry. RESULTS: In total, 12.6 and 1.7% of children had at least one FDR
      affected with type 1 or type 2 diabetes, respectively, and 6.6 and 34.8% had at
      least one grandparent with type 1 or type 2 diabetes. DKA (pH <7.30) occurred
      less frequently in children having a type 1 diabetes affected FDR (7.4 vs 20.5%,
      P<0.001). Type 2 diabetes among the parents or grandparents had no such effect.
      Lower risk HLA genotypes were observed to predispose to DKA (P<0.024). In a
      logistic regression analysis, the risk of DKA was independently associated with
      the absence of a family member affected by type 1 diabetes, the presence of a low
      risk HLA genotype and older age at diagnosis (odds ratio 3.23, 1.45 and 1.07
      respectively). CONCLUSION: The presence of type 1 diabetes in an FDR is
      associated with an decreased risk of DKA at diagnosis. The rate of DKA seems to
      be higher in children with lower HLA-conferred risk for type 1 diabetes.

PMID- 21890653
TI  - A search filter for increasing the retrieval of animal studies in Embase.
AB  - Collecting and analysing all available literature before starting a new animal
      experiment is important and it is indispensable when writing systematic reviews
      of animal research. In practice, finding all animal studies relevant to a
      specific research question turns out to be anything but simple. In order to
      facilitate this search process, we previously developed a search filter for
      retrieving animal studies in the most often used biomedical database, PubMed. It
      is a general requirement for systematic reviews, however, that at least two
      databases are searched. In this report, we therefore present a similar search
      filter for a second important database, namely Embase. We show that our filter
      retrieves more animal studies than (a combination of) the options currently
      available in Embase. Our search filters for PubMed and Embase therefore represent
      valuable tools for improving the quality of (systematic) reviews and thereby of
      new animal experiments.

PMID- 21890654
TI  - Successful treatment with bortezomib and thalidomide for POEMS syndrome
      associated with multicentric mixed-type Castleman's disease.
AB  - Polyneuropathy, organomegaly, endocrinopathy, M-protein and skin changes syndrome
      is a rare multi-systematic disorder of uncertain etiology, if associated with
      multicentric Castleman's disease, it can lead to a more serious condition. We
      here presented a case of polyneuropathy, organomegaly, endocrinopathy, M-protein
      and skin changes syndrome in a 37-year-old male patient who initially presented
      with progressive lower limb weakness accompanied by pain, low skin temperature,
      and hyperpigmentation. He was admitted with increasingly serious dyspnea and
      lower leg edema. Fluid of serous cavities in the patient were also indicated in
      ultrasonic inspection and X-ray. Furthermore, biopsy of a left axillary lymph
      node showed mixed hyaline-vascular and plasma cell type of multicentric
      Castleman's disease. Administration of bortezomib (Velcade) (1.3 mg/m(2) on days
      1, 4, 8 and 11 of a 21-day cycle) combined with thalidomide (100 mg/day and 21
      day cycle) dramatically improved the condition of this disease. Of note, in our
      study, combination therapy of bortezomib and thalidomide successfully improved
      the condition of the patient with polyneuropathy, organomegaly, endocrinopathy, M
      protein and skin changes syndrome associated with multicentric Castleman's
      disease, suggesting that the combination therapy may be an effective therapeutic
      strategy for the intractable polyneuropathy, organomegaly, endocrinopathy, M
      protein and skin changes syndrome associated with multicentric Castleman's
      disease.

PMID- 21890655
TI  - The history of the Gynecologic Cancer Study Group (GCSG) of the Japan Clinical
      Oncology Group (JCOG).
AB  - The Gynecologic Cancer Study Group (GCSG) of the Japan Clinical Oncology Group
      (JCOG) was organized in 1994. The GCSG has developed under the leadership of
      three successive group representatives, five principal study investigators, the
      cooperation of group members and the support of several public research funds. At
      present, 38 institutions are participating as active members of the GCSG of the
      JCOG. In addition to gynecologic oncologists, medical oncologists, pathologists
      and radiotherapists are participating in our group. Our group manages female
      genital malignancies including uterine cervical, endometrial, ovarian, tubal and
      vulvar cancers. Because the incidences of uterine cervical (in younger women),
      endometrial and ovarian cancer have increased in Japan in recent years, we are
      developing new standard treatments especially for these malignancies. As of 31
      May 2011, our group has conducted six JCOG clinical trials (three completed and
      three ongoing) and completed one JCOG accompanying study, which is now in
      preparation for publication. Our group has also conducted several retrospective
      studies, and Phase I and II trials independent of the JCOG Data Center. Our aim
      is to conduct unique and high-quality clinical trials which we can appeal to the
      world. In this review, we present the organization and achievements of our group,
      along with a list of participating institutions, as the history of the GCSG of
      the JCOG.

PMID- 21890656
TI  - Experimental arthritis triggers periodontal disease in mice: involvement of TNF
      alpha and the oral Microbiota.
AB  - Rheumatoid arthritis (RA) and periodontal disease (PD) are prevalent chronic
      inflammatory disorders that affect bone structures. Individuals with RA are more
      likely to experience PD, but how disease in joints could induce PD remains
      unknown. This study aimed to experimentally mimic clinical parameters of RA
      induced PD and to provide mechanistic findings to explain this association.
      Chronic Ag-induced arthritis (AIA) was triggered by injection of methylated BSA
      in the knee joint of immunized mice. Anti-TNF-alpha was used to assess the role
      of this cytokine. Intra-articular challenge induced infiltration of cells,
      synovial hyperplasia, bone resorption, proteoglycan loss, and increased
      expression of cytokines exclusively in challenged joints. Simultaneously, AIA
      resulted in severe alveolar bone loss, migration of osteoclasts, and release of
      proinflammatory cytokines in maxillae. Anti-TNF-alpha therapy prevented the
      development of both AIA and PD. AIA did not modify bacterial counts in the oral
      cavity. PD, but not AIA, induced by injection of Ag in immunized mice was
      decreased by local treatment with antiseptic, which decreased the oral
      microbiota. AIA was associated with an increase in serum C-reactive protein
      levels and the expression of the transcription factors RORgamma and Foxp3 in
      cervical lymph nodes. There were higher titers of anti-collagen I IgG, and
      splenocytes were more responsive to collagen I in AIA mice. In conclusion, AIA
      induced PD was dependent on TNF-alpha and the oral microbiota. Moreover, PD was
      associated with changes in expression of lymphocyte transcription factors,
      presence of anti-collagen Abs, and increased reactivity to autoantigens.

PMID- 21890657
TI  - A TLR5 agonist inhibits acute renal ischemic failure.
AB  - Reperfusion of ischemic organs induces a potent inflammatory response initiated
      by the generation of reactive oxygen species that directly damage tissue and
      promote leukocyte infiltration and activation that also mediate tissue injury. We
      recently found that radiation-induced tissue injury, which is caused by radiation
      induced reactive oxygen species, is attenuated by administration of CBLB502, a
      pharmacologically optimized derivative of the TLR5 agonist flagellin. Therefore,
      we tested the ability of CBLB502 to attenuate injury in a murine model of acute
      ischemic renal failure. CBLB502 given 30 min before imposition of bilateral renal
      pedicle occlusion provided marked protection against the renal dysfunction and
      inflammation that follows reperfusion of ischemic kidneys, including marked
      decreases in leukocyte infiltration, proinflammatory cytokine production, and
      tubular injury. Importantly, CBLB502 given within 30 min after ischemic kidney
      reperfusion reproduced the protective effects of pretreatment with the TLR5
      agonist, indicating a window following reperfusion in which CBLB502
      administration abrogates acute renal ischemic failure. Bone marrow-reconstituted
      chimeras were used to show that the protective effects of CBLB502 could be
      delivered by intact MyD88 signaling on renal parenchymal cells. Consistent with
      this, Ab staining of kidney sections indicated that cells lining the renal
      vasculature expressed TLR5. Overall, these results indicate the use of TLR5
      agonists as mitigators and protectants of acute renal ischemic failure.

PMID- 21890658
TI  - Functional CD8 T cell memory responding to persistent latent infection is
      maintained for life.
AB  - Aging is associated with depressed naive T cell responses, but it is less clear
      whether T cell memory established early in life also becomes impaired with age.
      This is particularly important for T cells responding to latent persistent
      infection, which need to remain functional and capable of controlling the
      infection over the lifetime; however, repeated stimulation over the lifetime may
      dysregulate their maintenance or function, potentially contributing to impaired
      immunity in the elderly. Systemic infection with HSV-1, a persistent latent
      virus, is associated with memory inflation of virus-specific CD8 T cells. We
      tested how these inflated memory cells are maintained from adulthood into old
      age. We found no significant differences in the numbers (i.e., blood, spleen), ex
      vivo Ag-specific IFN-gamma production, and in vivo recall response to HSV-1
      (i.e., proliferation, IFN-gamma production, cytolysis) between adult and old
      memory T cells. There was a discrete shift from dominantly effector memory
      phenotype in the adults to a central memory-like phenotype in the old mice, with
      fewer old cells expressing the killer cell lectin-like receptor G1 (KLRG1). Adult
      and old KLRG1(+) memory CD8 T cells were functionally identical: both produced
      IFN-gamma but could minimally proliferate in response to viral challenge.
      Interestingly, regardless of age, KLRG1(+) cells retained the ability to
      proliferate and survive in response to homeostatic signals, both in vitro
      (culture with IL-7 and IL-15) and in vivo (expansion following transfer into
      lymphopenic recipients). This finding demonstrates that functional effector
      memory T cells, including those expressing KLRG-1, are maintained and are
      functional for life, despite the presence of persistent viral infection.

PMID- 21890659
TI  - Selenite induces posttranscriptional blockade of HLA-E expression and sensitizes
      tumor cells to CD94/NKG2A-positive NK cells.
AB  - CD94/NKG2A is an inhibitory receptor that controls the activity of a large
      proportion of human NK cells following interactions with the nonclassical HLA
      class Ib molecule HLA-E expressed on target cells. In this study, we show that
      selenite (SeO(3)(2-)), an inorganic selenium compound, induces an almost complete
      loss of cell surface expression of HLA-E on tumor cells of various origins.
      Selenite abrogated the HLA-E expression at a posttranscriptional level, since
      selenite exposure led to a dose-dependent decrease in cellular HLA-E protein
      expression whereas the mRNA levels remained intact. The loss of HLA-E expression
      following selenite treatment was associated with decreased levels of
      intracellular free thiols in the tumor cells, suggesting that the reduced HLA-E
      protein synthesis was caused by oxidative stress. Indeed, HLA-E expression and
      the level of free thiols remained intact following treatment with
      selenomethionine, a selenium compound that does not generate oxidative stress.
      Loss of HLA-E expression, but not of total HLA class I expression, on tumor cells
      resulted in increased susceptibility to CD94/NK group 2A-positive NK cells. Our
      results suggest that selenite may be used to potentiate the anti-tumor
      cytotoxicity in settings of NK cell-based immunotherapies.

PMID- 21890660
TI  - Macrophages at the fetal-maternal interface express markers of alternative
      activation and are induced by M-CSF and IL-10.
AB  - During pregnancy, the maternal immune system is challenged by the presence of the
      fetus, which must be tolerated despite being semiallogeneic. Uterine mucosal (or
      decidual) macrophages (M), one of the major leukocyte populations at the fetal
      maternal interface, have been implicated in fetal tolerance, but information
      regarding their regulation is scarce. In this study, we investigated the role of
      several factors potentially involved in the differentiation and polarization of
      decidual M with an in vitro M differentiation model. By using flow cytometry, we
      showed that M-CSF and IL-10 were potent inducers of M2 (immunoregulatory) M
      markers expressed on human decidual M (CD14, CD163, CD206, CD209). In contrast,
      proinflammatory stimuli, and unexpectedly also the Th2-associated IL-4 and IL-13,
      induced different patterns of expression, indicating that a Th2-dominated
      environment is not required for decidual M polarization. M-CSF/IL-10-stimulated
      and decidual M also showed similar cytokine secretion patterns, with production
      of IL-10 as well as IL-6, TNF, and CCL4. Conversely, the proinflammatory, LPS/IFN
      gamma-stimulated M produced significantly higher levels of TNF and no IL-10. We
      also used a gene array with 420 M-related genes, of which 100 were previously
      reported to be regulated in a global gene expression profiling of decidual M,
      confirming that M-CSF/IL-10-induced M are closely related to decidual M. Taken
      together, our results consistently point to a central role for M-CSF and in
      particular IL-10 in the shaping of decidual M with regulatory properties. These
      cytokines may therefore play an important role in supporting the homeostatic and
      tolerant immune milieu required for a successful pregnancy.

PMID- 21890662
TI  - Mechanosensitivity before and after hysterectomy: a prospective study on the
      prediction of acute and chronic postoperative pain.
AB  - BACKGROUND: The incidence of chronic pain after hysterectomy is reported to be up
      to 30%, but the relative role of different pathogenic factors has not been
      defined. This study aimed to assess the predictive value of preoperative
      abdominal and vaginal mechanosensitivity for the subsequent development of acute
      and chronic pain after hysterectomy. METHODS: Ninety women undergoing
      hysterectomy for benign conditions were studied. Experimental testing was carried
      out on the day before hysterectomy, on the first postoperative day, and after 4
      months. Abdominal testing included brush-evoked allodynia, pinprick hyperalgesia,
      wind-up-like pain, and pressure pain thresholds. Vaginal testing included
      pressure pain thresholds. The intensity of pelvic pain was recorded on a
      numerical rating scale before hysterectomy, daily in the first postoperative
      week, and after 4 months. RESULTS: The incidence of pelvic pain was 51% before
      hysterectomy and 17% after 4 months. Before hysterectomy, brush-evoked allodynia
      and pinprick hyperalgesia were more frequent in women with pelvic pain (P=0.04
      and 0.02, respectively), with abdominal and vaginal pressure pain thresholds
      being lower in those with preoperative pelvic pain (P=0.04 and <0.01,
      respectively). Preoperative brush-evoked allodynia, pinprick hyperalgesia, and
      vaginal pressure pain threshold were associated with the intensity of acute
      postoperative pain (P=0.04, <0.01, and <0.01, respectively). Preoperative brush
      evoked allodynia was also associated with pelvic pain after 4 months (P<0.01).
      CONCLUSIONS: Preoperative pain sensitization as reflected by cutaneous and
      vaginal hypersensitivity is associated with acute pain after hysterectomy, but
      less so with persistent pain.

PMID- 21890661
TI  - Incidence and predictors of major perioperative adverse cardiac and
      cerebrovascular events in non-cardiac surgery.
AB  - BACKGROUND: Major adverse cardiac and cerebrovascular events (MACCE) represent
      the most common cause of serious perioperative morbidity and mortality. Our aim
      was to identify risk factors for MACCE in a broad surgical population with
      intermediate-to-high surgery-specific risk and to build and validate a model to
      predict the risk of MACCE. METHODS: A prospective, multicentre study of patients
      undergoing surgical procedures under general or regional anaesthesia in 23
      hospitals. The main outcome was the occurrence of at least one perioperative
      MACCE, defined as any of the following complications from admittance to
      discharge: cardiac death, cerebrovascular death, non-fatal cardiac arrest, acute
      myocardial infarction, congestive heart failure, new cardiac arrhythmia, angina,
      or stroke. The MACCE predictive index was based on beta-coefficients and
      validated in an external data set. RESULTS: Of 3387 patients recruited, 146
      (4.3%) developed at least one MACCE. The regression model identified seven
      independent risk factors for MACCE: history of coronary artery disease, history
      of chronic congestive heart failure, chronic kidney disease, history of
      cerebrovascular disease, preoperative abnormal ECG, intraoperative hypotension,
      and blood transfusion. The area under the receiver-operating characteristic curve
      was 75.9% (95% confidence interval, 71.2-80.6%). CONCLUSIONS: The risk score
      based on seven objective and easily assessed factors can accurately predict MACCE
      occurrence after non-cardiac surgery in a population at intermediate-to-high
      surgery-specific risk.

PMID- 21890663
TI  - Shedding of the coronary endothelial glycocalyx: effects of hypoxia/reoxygenation
      vs ischaemia/reperfusion.
AB  - BACKGROUND: Vascular endothelium is covered by a glycocalyx. Damage to the
      glycocalyx after systemic inflammation or ischaemia/reperfusion contributes to
      increased vascular permeability and leucocyte adhesion. The underlying mechanisms
      leading to ischaemia/reperfusion-induced glycocalyx shedding are incompletely
      understood, in terms of lack of oxygen, absence of flow, or return of oxygen.
      METHODS: Isolated guinea pig hearts perfused with Krebs-Henseleit buffer at 37
      degrees C underwent 20 min of either stopped-flow ischaemia or hypoxic perfusion
      with subsequent reperfusion/reoxygenation (n = 6 each). Hearts perfused with
      normoxic buffer served as time controls. Epicardial transudate was collected to
      assess coronary net fluid filtration, colloid extravasation, and histamine
      release by mast cells. Syndecan-1 and heparan sulphate were measured in coronary
      effluent, together with lactate, purines, and the release of mast-cell tryptase
      beta. Additional hearts were perfusion-fixed to visualize the glycocalyx.
      RESULTS: Both ischaemia and hypoxia with reperfusion/reoxygenation resulted in
      significant increases in net fluid filtration (P < 0.05) and release of syndecan
      1 and heparan sulphate in coronary effluent. These effects were already seen with
      the onset of hypoxic perfusion. Histamine was released during hypoxia and
      reoxygenation and also reperfusion, as was tryptase beta, and high concentrations
      of adenosine (>1 umol litre-1, hypoxia group) and inosine (> 7 umol litre-1,
      ischaemia group) were measured in effluent (P < 0.05). Damage to the coronary
      glycocalyx was evident upon electron microscopy. CONCLUSIONS: Both ischaemic and
      hypoxic hypoxia initiate glycocalyx degradation, promoting an increase in
      permeability. A contributing mechanism could be purine-mediated degranulation of
      resident mast cells, with liberated tryptase beta acting as potential 'sheddase'.

PMID- 21890664
TI  - Functional analyses of multiple lichenin-degrading enzymes from the rumen
      bacterium Ruminococcus albus 8.
AB  - Ruminococcus albus 8 is a fibrolytic ruminal bacterium capable of utilization of
      various plant cell wall polysaccharides. A bioinformatic analysis of a partial
      genome sequence of R. albus revealed several putative enzymes likely to hydrolyze
      glucans, including lichenin, a mixed-linkage polysaccharide of glucose linked
      together in beta-1,3 and beta-1,4 glycosidic bonds. In the present study, we
      demonstrate the capacity of four glycoside hydrolases (GHs), derived from R.
      albus, to hydrolyze lichenin. Two of the genes encoded GH family 5 enzymes
      (Ra0453 and Ra2830), one gene encoded a GH family 16 enzyme (Ra0505), and the
      last gene encoded a GH family 3 enzyme (Ra1595). Each gene was expressed in
      Escherichia coli, and the recombinant protein was purified to near homogeneity.
      Upon screening on a wide range of substrates, Ra0453, Ra2830, and Ra0505
      displayed different hydrolytic properties, as they released unique product
      profiles. The Ra1595 protein, predicted to function as a beta-glucosidase,
      preferred cleavage of a nonreducing end glucose when linked by a beta-1,3
      glycosidic bond to the next glucose residue. The major product of Ra0505
      hydrolysis of lichenin was predicted to be a glucotriose that was degraded only
      by Ra0453 to glucose and cellobiose. Most importantly, the four enzymes
      functioned synergistically to hydrolyze lichenin to glucose, cellobiose, and
      cellotriose. This lichenin-degrading enzyme mix should be of utility as an
      additive to feeds administered to monogastric animals, especially those high in
      fiber.

PMID- 21890665
TI  - Rapid, transient, and proportional activation of sigma(B) in response to osmotic
      stress in Listeria monocytogenes.
AB  - The osmotic activation of sigma B (sigma(B)) in Listeria monocytogenes was
      studied by monitoring expression of four known sigma(B)-dependent genes, opuCA,
      lmo2230, lmo2085, and sigB. Activation was found to be rapid, transient, and
      proportional to the magnitude of the osmotic stress applied, features that
      underpin the adaptability of this pathogen.

PMID- 21890666
TI  - Microcolony formation by single-cell Synechococcus strains as a fast response to
      UV radiation.
AB  - UV radiation (UVR) has different effects on prokaryotic cells, such as, for
      instance, filamentation and aggregation in bacteria. Here we studied the effect
      of UVR on microcolony formation in two freshwater Synechococcus strains of
      different ribotypes (group B and group I) and phycobiliprotein compositions
      (phycoerythrin [PE] and phycocyanin [PC]). Each strain was photoacclimated at two
      light intensities, low light (LL) (10 MUmol m-2 s-1) and moderate light (ML) (100
      MUmol m-2 s-1). The cultures were exposed for 6 days to treatments with UVR or
      without UVR. PE-rich Synechococcus acclimated to LL had a low
      carotenoid/chlorophyll a (car/chl) ratio but responded faster to UVR treatment,
      producing the highest percentages of microcolonies and of cells in microcolonies.
      Conversely, the same strain acclimated to ML, with a higher car/chl ratio, did
      not aggregate significantly. These results suggest that microcolony formation by
      PE-rich Synechococcus is induced by UVR if carotenoid levels are low. PC-rich
      Synechococcus formed a very low percentage of microcolonies in both acclimations
      even with low car/chl ratio. The different responses of the two Synechococcus
      strains to UVR depend on their pigment compositions. On the other hand, this
      study does not exclude that UVR-induced microcolony formation could also be
      related to specific ribotypes.

PMID- 21890667
TI  - Phage specificity of the freshwater fish pathogen Flavobacterium columnare.
AB  - Flavobacteria and their phages were isolated from Finnish freshwaters and fish
      farms. Emphasis was placed on finding phages infecting the fish pathogen
      Flavobacterium columnare for use as phage therapy agents. The host ranges of the
      flavobacterial phages varied, phages infecting F. columnare being more host
      specific than the other phages.

PMID- 21890668
TI  - The Lcn972 bacteriocin-encoding plasmid pBL1 impairs cellobiose metabolism in
      Lactococcus lactis.
AB  - pBL1 is a Lactococcus lactis theta-replicating 10.9-kbp plasmid that encodes the
      synthetic machinery of the bacteriocin Lcn972. In this work, the transcriptomes
      of exponentially growing L. lactis strains with and without pBL1 were compared. A
      discrete response was observed, with a total of 10 genes showing significantly
      changed expression. Upregulation of the lactococcal oligopeptide uptake (opp)
      system was observed, which was likely linked to a higher nitrogen demand required
      for Lcn972 biosynthesis. Strikingly, celB, coding for the membrane porter IIC of
      the cellobiose phosphoenolpyruvate-dependent phosphotransferase system (PTS), and
      the upstream gene llmg0186 were downregulated. Growth profiles for L. lactis
      strains MG1363, MG1363/pBL1, and MG1363 DeltacelB grown in chemically defined
      medium (CDM) containing cellobiose confirmed slower growth of MG1363/pBL1 and
      MG1363 DeltacelB, while no differences were observed with growth on glucose. The
      presence of pBL1 shifted the fermentation products toward a mixed acid profile
      and promoted substantial changes in intracellular pool sizes for glycolytic
      intermediates in cells growing on cellobiose as determined by high-pressure
      liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Overall, these
      data support the genetic evidence of a constriction in cellobiose uptake.
      Notably, several cell wall precursors accumulated, while other UDP-activated
      sugar pools were lower, which could reflect rerouting of precursors toward the
      production of structural or storage polysaccharides. Moreover, cells growing
      slowly on cellobiose and those lacking celB were more tolerant to Lcn972 than
      cellobiose-adapted cells. Thus, downregulation of celB could help to build up a
      response against the antimicrobial activity of Lcn972, enhancing self-immunity of
      the producer cells.

PMID- 21890669
TI  - Barcoded primers used in multiplex amplicon pyrosequencing bias amplification.
AB  - "Barcode-tagged" PCR primers used for multiplex amplicon sequencing generate a
      thus-far-overlooked amplification bias that produces variable terminal
      restriction fragment length polymorphism (T-RFLP) and pyrosequencing data from
      the same environmental DNA template. We propose a simple two-step PCR approach
      that increases reproducibility and consistently recovers higher genetic diversity
      in pyrosequencing libraries.

PMID- 21890670
TI  - Contribution of a sodium ion gradient to energy conservation during fermentation
      in the cyanobacterium Arthrospira (Spirulina) maxima CS-328.
AB  - Sodium gradients in cyanobacteria play an important role in energy storage under
      photoautotrophic conditions but have not been well studied during
      autofermentative metabolism under the dark, anoxic conditions widely used to
      produce precursors to fuels. Here we demonstrate significant stress-induced
      acceleration of autofermentation of photosynthetically generated carbohydrates
      (glycogen and sugars) to form excreted organic acids, alcohols, and hydrogen gas
      by the halophilic, alkalophilic cyanobacterium Arthrospira (Spirulina) maxima CS
      328. When suspended in potassium versus sodium phosphate buffers at the start of
      autofermentation to remove the sodium ion gradient, photoautotrophically grown
      cells catabolized more intracellular carbohydrates while producing 67% higher
      yields of hydrogen, acetate, and ethanol (and significant amounts of lactate) as
      fermentative products. A comparable acceleration of fermentative carbohydrate
      catabolism occurred upon dissipating the sodium gradient via addition of the
      sodium-channel blocker quinidine or the sodium-ionophore monensin but not upon
      dissipating the proton gradient with the proton-ionophore dinitrophenol (DNP).
      The data demonstrate that intracellular energy is stored via a sodium gradient
      during autofermentative metabolism and that, when this gradient is blocked, the
      blockage is compensated by increased energy conversion via carbohydrate
      catabolism.

PMID- 21890671
TI  - Detection of enterotoxigenic Clostridium perfringens in meat samples by using
      molecular methods.
AB  - To prevent food-borne bacterial diseases and to trace bacterial contamination
      events to foods, microbial source tracking (MST) methods provide important
      epidemiological information. To apply molecular methods to MST, it is necessary
      not only to amplify bacterial cells to detection limit levels but also to prepare
      DNA with reduced inhibitory compounds and contamination. Isolates carrying the
      Clostridium perfringens enterotoxin gene (cpe) on the chromosome or a plasmid
      rank among the most important food-borne pathogens. Previous surveys indicated
      that cpe-positive C. perfringens isolates are present in only ~5% of nonoutbreak
      food samples and then only at low numbers, usually less than 3 cells/g. In this
      study, four molecular assays for the detection of cpe-positive C. perfringens
      isolates, i.e., ordinary PCR, nested PCR, real-time PCR, and loop-mediated
      isothermal amplification (LAMP), were developed and evaluated for their
      reliability using purified DNA. For use in the artificial contamination of meat
      samples, DNA templates were prepared by three different commercial DNA
      preparation kits. The four molecular assays always detected cpe when >103 cells/g
      of cpe-positive C. perfringens were present, using any kit. Of three tested
      commercial DNA preparation kits, the InstaGene matrix kit appeared to be most
      suitable for the testing of a large number of samples. By using the InstaGene
      matrix kit, the four molecular assays efficiently detected cpe using DNA prepared
      from enrichment culture specimens of meat samples contaminated with low numbers
      of cpe-positive C. perfringens vegetative cells or spores. Overall, the current
      study developed molecular assay protocols for MST to detect the contamination of
      foods with low numbers of cells, and at a low frequency, of cpe-positive C.
      perfringens isolates.

PMID- 21890672
TI  - Spatial variations in archaeal lipids of surface water and core-top sediments in
      the South china sea and their implications for paleoclimate studies.
AB  - The South China Sea (SCS) is the largest marginal sea of the western Pacific
      Ocean, yet little is known about archaeal distributions and TEX86-based
      temperatures in this unique oceanic setting. Here we report findings of
      abundances in both core lipids (CL) and intact polar lipids (IPL) of Archaea from
      surface water (CL only) and core-top sediments from different regions of the SCS.
      TEX86-derived temperatures were also calculated for these samples. The surface
      water had extremely low abundances of CL (average of 0.05 +/- 0.13 ng/liter; n =
      75), with higher values present in regions where upwelling is known to occur. The
      core-top sediments had CL values of 0.1 to 0.9 MUg/g, which are on the low end of
      CL concentrations reported for other marine sediments and may reflect the
      oligotrophic nature of the open SCS. The IPL of Archaea accounted for 6 to 36.4%
      of total lipids (CL plus IPL), indicating that the majority of archaeal lipids in
      core-top sediments were derived from nonliving cells. The TEX86-based
      temperatures of surface water were overall lower than satellite-based sea surface
      temperatures or CTD-measured in situ temperatures. The core-top sediment samples,
      however, had TEX86 temperatures very close to the mean annual sea surface
      temperatures, except for samples with water depths of less than 100 m. Our
      results demonstrated low and heterogeneous distributions of archaeal lipids in
      surface water and core-top sediments of the SCS, which may reflect local or
      regional differences in productivity of Archaea. While TEX86-based temperatures
      for core-top marine sediments at deep water depths (>100 m) generally reflected
      mean annual sea surface temperatures, TEX86 temperatures in surface water varied
      basin wide and underestimated sea surface temperatures in most locations for the
      season when surface water samples were collected.

PMID- 21890673
TI  - Selective utilization of exogenous amino acids by Dehalococcoides ethenogenes
      strain 195 and its effects on growth and dechlorination activity.
AB  - Bacteria of the genus Dehalococcoides are important members of bioremediation
      communities because of their ability to detoxify chloroethenes to the benign end
      product ethene. Genome-enabled studies conducted with Dehalococcoides ethenogenes
      195 have revealed that two ATP-binding cassette (ABC)-type amino acid
      transporters are expressed during its exponential growth stages. In light of
      previous findings that Casamino Acids enhanced its dechlorination activity, we
      hypothesized that strain 195 is capable of importing amino acids from its
      environment to facilitate dechlorination and growth. To test this hypothesis, we
      applied isotopomer-based dilution analysis with (13)C-labeled acetate to
      differentiate the amino acids that were taken up by strain 195 from those
      synthesized de novo and to determine the physiological changes caused by the
      significantly incorporated amino acids. Our results showed that
      glutamate/glutamine and aspartate/asparagine were almost exclusively synthesized
      by strain 195, even when provided in excess in the medium. In contrast,
      phenylalanine, isoleucine, leucine, and methionine were identified as the four
      most highly incorporated amino acids, at levels >30% of respective proteinogenic
      amino acids. When either phenylalanine or all four highly incorporated amino
      acids were added to the defined mineral medium, the growth rates, dechlorination
      activities, and yields of strain 195 were enhanced to levels similar to those
      observed with supplementation with 20 amino acids. However, genes for the
      putative ABC-type amino acids transporters and phenylalanine biosynthesis
      exhibited insignificant regulation in response to the imported amino acids. This
      study also demonstrates that using isotopomer-based metabolite analysis can be an
      efficient strategy for optimizing nutritional conditions for slow-growing
      microorganisms.

PMID- 21890674
TI  - Active autotrophic ammonia-oxidizing bacteria in biofilm enrichments from
      simulated creek ecosystems at two ammonium concentrations respond to temperature
      manipulation.
AB  - The first step of nitrification, the oxidation of ammonia to nitrite, is
      important for reducing eutrophication in freshwater environments when coupled
      with anammox (anaerobic ammonium oxidation) or denitrification. We analyzed
      active formerly biofilm-associated aerobic ammonia-oxidizing communities
      originating from Ammerbach (AS) and Leutra South (LS) stream water (683 +/- 550
      [mean +/- standard deviation] and 16 +/- 7 MUM NH(4)(+), respectively) that were
      developed in a flow-channel experiment and incubated under three temperature
      regimens. By stable-isotope probing using (13)CO(2), we found that members of the
      Bacteria and not Archaea were the functionally dominant autotrophic ammonia
      oxidizers at all temperatures under relatively high ammonium loads. The copy
      numbers of bacterial amoA genes in (13)C-labeled DNA were lower at 30 degrees C
      than at 13 degrees C in both stream enrichment cultures. However, the community
      composition of the ammonia-oxidizing bacteria (AOB) in the (13)C-labeled DNA
      responded differently to temperature manipulation at two ammonium concentrations.
      In LS enrichments incubated at the in situ temperature (13 degrees C),
      Nitrosomonas oligotropha-like sequences were retrieved with sequences from
      Nitrosospira AmoA cluster 4, while the proportion of Nitrosospira sequences
      increased at higher temperatures. In AS enrichments incubated at 13 degrees C and
      20 degrees C, AmoA cluster 4 sequences were dominant; Nitrosomonas nitrosa-like
      sequences dominated at 30 degrees C. Biofilm-associated AOB communities were
      affected differentially by temperature at two relatively high ammonium
      concentrations, implicating them in a potential role in governing contaminated
      freshwater AOB distributions.

PMID- 21890676
TI  - Influence of a bacteriophage on the population dynamics of toxic dinoflagellates
      by lysis of algicidal bacteria.
AB  - A lytic phage (oZCW1) was isolated from an algicidal bacterium Pseudoalteromonas
      sp. strain SP48 that specifically kills the toxic dinoflagellate Alexandrium
      tamarense. We demonstrated that oZCW1 could trigger the growth of A. tamarense by
      inhibiting the growth of algicidal bacterium SP48. In contrast, the growth of A.
      tamarense was suppressed when cocultured with either SP48 or the oZCW1-resistant
      mutant of SP48. This study provides the first evidence of the indirect impact of
      bacteriophage on bloom-forming microalgae via phage lysis of alga-killing
      bacteria.

PMID- 21890675
TI  - Fine-scale distribution patterns of Synechococcus ecological diversity in
      microbial mats of Mushroom Spring, Yellowstone National Park.
AB  - Past analyses of sequence diversity in high-resolution protein-encoding genes
      have identified putative ecological species of unicellular cyanobacteria in the
      genus Synechococcus, which are specialized to 60 degrees C but not 65 degrees C
      in Mushroom Spring microbial mats. Because these studies were limited to only two
      habitats, we studied the distribution of Synechococcus sequence variants at 1
      degrees C intervals along the effluent flow channel and at 80-MUm vertical-depth
      intervals throughout the upper photic layer of the microbial mat. Diversity at
      the psaA locus, which encodes a photosynthetic reaction center protein (PsaA),
      was sampled by PCR amplification, cloning, and sequencing methods at 60, 63, and
      65 degrees C sites. The evolutionary simulation programs Ecotype Simulation and
      AdaptML were used to identify putative ecologically distinct populations
      (ecotypes). Ecotype Simulation predicted a higher number of putative ecotypes in
      cases where habitat variation was limited, while AdaptML predicted a higher
      number of ecologically distinct phylogenetic clades in cases where habitat
      variation was high. Denaturing gradient gel electrophoresis was used to track the
      distribution of dominant sequence variants of ecotype populations relative to
      temperature variation and to O2, pH, and spectral irradiance variation, as
      measured using microsensors. Different distributions along effluent channel flow
      and vertical gradients, where temperature, light, and O2 concentrations are known
      to vary, confirmed the ecological distinctness of putative ecotypes.

PMID- 21890677
TI  - Identification and characterization of Sclerotinia sclerotiorum NADPH oxidases.
AB  - Numerous studies have shown both the detrimental and beneficial effects of
      reactive oxygen species (ROS) in animals, plants, and fungi. These organisms
      utilize controlled generation of ROS for signaling, pathogenicity, and
      development. Here, we show that ROS are essential for the pathogenic development
      of Sclerotinia sclerotiorum, an economically important fungal pathogen with a
      broad host range. Based on the organism's completed genome sequence, we
      identified two S. sclerotiorum NADPH oxidases (SsNox1 and SsNox2), which
      presumably are involved in ROS generation. RNA interference (RNAi) was used to
      examine the function of SsNox1 and SsNox2. Silencing of SsNox1 expression
      indicated a central role for this enzyme in both virulence and pathogenic
      (sclerotial) development, while inactivation of the SsNox2 gene resulted in
      limited sclerotial development, but the organism remained fully pathogenic.
      DeltaSsnox1 strains had reduced ROS levels, were unable to develop sclerotia, and
      unexpectedly correlated with significantly reduced oxalate production. These
      results are in accordance with previous observations indicating that fungal NADPH
      oxidases are required for pathogenic development and are consistent with the
      importance of ROS regulation in the successful pathogenesis of S. sclerotiorum.

PMID- 21890678
TI  - Effect of genetically modified poplars on soil microbial communities during the
      phytoremediation of waste mine tailings.
AB  - The application of transgenic plants to clean up environmental pollution caused
      by the wastes of heavy metal mining is a promising method for removing metal
      pollutants from soils. However, the effect of using genetically modified
      organisms for phytoremediation is a poorly researched topic in terms of microbial
      community structures, despite the important role of microorganisms in the health
      of soil. In this study, a comparative analysis of the bacterial and archaeal
      communities found in the rhizosphere of genetically modified (GM) versus wild
      type (WT) poplar was conducted on trees at different growth stages (i.e., the
      rhizospheres of 1.5-, 2.5-, and 3-year-old poplars) that were cultivated on
      contaminated soils together with nonplanted control soil. Based on the results of
      DNA pyrosequencing, poplar type and growth stages were associated with
      directional changes in the structure of the microbial community. The rate of
      change was faster in GM poplars than in WT poplars, but the microbial communities
      were identical in the 3-year-old poplars. This phenomenon may arise because of a
      higher rate and greater extent of metal accumulation in GM poplars than in
      naturally occurring plants, which resulted in greater changes in soil
      environments and hence the microbial habitat.

PMID- 21890679
TI  - An exometabolomics approach to monitoring microbial contamination in microalgal
      fermentation processes by using metabolic footprint analysis.
AB  - The early detection of microbial contamination is crucial to avoid process
      failure and costly delays in fermentation industries. However, traditional
      detection methods such as plate counting and microscopy are labor-intensive,
      insensitive, and time-consuming. Modern techniques that can detect microbial
      contamination rapidly and cost-effectively are therefore sought. In the present
      study, we propose gas chromatography-mass spectrometry (GC-MS)-based metabolic
      footprint analysis as a rapid and reliable method for the detection of microbial
      contamination in fermentation processes. Our metabolic footprint analysis
      detected statistically significant differences in metabolite profiles of axenic
      and contaminated batch cultures of microalgae as early as 3 h after contamination
      was introduced, while classical detection methods could detect contamination only
      after 24 h. The data were analyzed by discriminant function analysis and were
      validated by leave-one-out cross-validation. We obtained a 97% success rate in
      correctly classifying samples coming from contaminated or axenic cultures.
      Therefore, metabolic footprint analysis combined with discriminant function
      analysis presents a rapid and cost-effective approach to monitor microbial
      contamination in industrial fermentation processes.

PMID- 21890680
TI  - Characterization of complex chromosomal rearrangements by targeted capture and
      next-generation sequencing.
AB  - Translocations are a common class of chromosomal aberrations and can cause
      disease by physically disrupting genes or altering their regulatory environment.
      Some translocations, apparently balanced at the microscopic level, include
      deletions, duplications, insertions, or inversions at the molecular level.
      Traditionally, chromosomal rearrangements have been investigated with a
      conventional banded karyotype followed by arduous positional cloning projects.
      More recently, molecular cytogenetic approaches using fluorescence in situ
      hybridization (FISH), array comparative genomic hybridization (aCGH), or whole
      genome SNP genotyping together with molecular methods such as inverse PCR and
      quantitative PCR have allowed more precise evaluation of the breakpoints. These
      methods suffer, however, from being experimentally intensive and time-consuming
      and of less than single base pair resolution. Here we describe targeted
      breakpoint capture followed by next-generation sequencing (TBCS) as a new
      approach to the general problem of determining the precise structural
      characterization of translocation breakpoints and related chromosomal
      aberrations. We tested this approach in three patients with complex chromosomal
      translocations: The first had craniofacial abnormalities and an apparently
      balanced t(2;3)(p15;q12) translocation; the second has cleidocranial dysplasia
      (OMIM 119600) associated with a t(2;6)(q22;p12.3) translocation and a breakpoint
      in RUNX2 on chromosome 6p; and the third has acampomelic campomelic dysplasia
      (OMIM 114290) associated with a t(5;17)(q23.2;q24) translocation, with a
      breakpoint upstream of SOX9 on chromosome 17q. Preliminary studies indicated
      complex rearrangements in patients 1 and 3 with a total of 10 predicted
      breakpoints in the three patients. By using TBCS, we quickly and precisely
      defined eight of the 10 breakpoints.

PMID- 21890682
TI  - Making competition work in the English NHS: the case for maintaining regulated
      prices.

PMID- 21890681
TI  - Genome-wide analysis distinguishes hyperglycemia regulated epigenetic signatures
      of primary vascular cells.
AB  - Emerging evidence suggests that poor glycemic control mediates post-translational
      modifications to the H3 histone tail. We are only beginning to understand the
      dynamic role of some of the diverse epigenetic changes mediated by hyperglycemia
      at single loci, yet elevated glucose levels are thought to regulate genome-wide
      changes, and this still remains poorly understood. In this article we describe
      genome-wide histone H3K9/K14 hyperacetylation and DNA methylation maps conferred
      by hyperglycemia in primary human vascular cells. Chromatin immunoprecipitation
      (ChIP) as well as CpG methylation (CpG) assays, followed by massive parallel
      sequencing (ChIP-seq and CpG-seq) identified unique hyperacetylation and CpG
      methylation signatures with proximal and distal patterns of regionalization
      associative with gene expression. Ingenuity knowledge-based pathway and gene
      ontology analyses indicate that hyperglycemia significantly affects human
      vascular chromatin with the transcriptional up-regulation of genes involved in
      metabolic and cardiovascular disease. We have generated the first installment of
      a reference collection of hyperglycemia-induced chromatin modifications using
      robust and reproducible platforms that allow parallel sequencing-by-synthesis of
      immunopurified content. We uncover that hyperglycemia-mediated induction of genes
      and pathways associated with endothelial dysfunction occur through modulation of
      acetylated H3K9/K14 inversely correlated with methyl-CpG content.

PMID- 21890683
TI  - Provider diversity in the English NHS: a study of recent developments in four
      local health economies.
AB  - OBJECTIVES: To assess the impact of provider diversity on quality and innovation
      in the English NHS by mapping the extent of diverse provider activity and
      identifying the differences in performance between Third Sector Organisations
      (TSOs), for-profit private enterprises, and incumbent organizations within the
      NHS, and the factors that affect the entry and growth of new providers. METHODS:
      Case studies of four local health economies. Data included: semi-structured
      interviews with 48 managerial and clinical staff from NHS organizations and
      providers from the private and third sector; some documentary evidence; a focus
      group with service users; and routine data from the Care Quality Commission and
      Companies House. Data collection was mainly between November 2008 and November
      2009. RESULTS: Involvement of diverse providers in the NHS is limited.
      Commissioners' local strategies influence degrees of diversity. Barriers to entry
      for TSOs include lack of economies of scale in the bidding process. Private
      providers have greater concern to improve patient pathways and patient
      experience, whereas TSOs deliver quality improvements by using a more holistic
      approach and a greater degree of community involvement. Entry of new providers
      drives NHS trusts to respond by making improvements. Information sharing
      diminishes as competition intensifies. CONCLUSIONS: There is scope to increase
      the participation of diverse providers in the NHS but care must be taken not to
      damage public accountability, overall productivity, equity and NHS providers
      (especially acute hospitals, which are likely to remain in the NHS) in the
      process.

PMID- 21890684
TI  - Prospects for knowledge exchange in health policy and management: institutional
      and epistemic boundaries.
AB  - OBJECTIVES: There have been calls for greater exchange between research and
      practice in health care policy and management, but little empirical research on
      what commissioners of research and researchers themselves consider appropriate,
      good quality research knowledge. This paper addresses this gap, considering the
      views of commissioners and producers of policy and management research in health
      care and other fields. METHODS: Qualitative semi-structured interviews with 18
      commissioners and producers of research, in central government, the NHS and other
      commissioning organizations, and in universities and independent sector
      providers. RESULTS: Commissioners and producers agreed that research often fails
      to fulfil policy-makers' and managers' needs, and that greater interaction is
      required to improve this relationship. However, they offered differing accounts
      of the nature of research knowledge (as a 'product' or a 'mindset'), and of what
      constitutes value, validity and originality in research, reflecting the differing
      priorities and pressures faced by the two groups. CONCLUSIONS: Efforts to promote
      greater interaction between research, policy and practice, and more critical,
      reflexive engagement between policy-makers, managers and researchers, are likely
      to face significant obstacles given these competing constructions of research
      knowledge and their reinforcement by divergent priorities.

PMID- 21890685
TI  - Dehydroepiandrosterone inhibits the Src/STAT3 constitutive activation in
      pulmonary arterial hypertension.
AB  - Pulmonary arterial hypertension (PAH) is an obstructive vasculopathy
      characterized by enhanced pulmonary artery smooth muscle cell (PASMC)
      proliferation and suppressed apoptosis. This phenotype is sustained by the
      activation of the Src/signal transducer and activator of transcription 3 (STAT3)
      axis, maintained by a positive feedback loop involving miR-204 and followed by an
      aberrant expression/activation of its downstream targets such as Pim1 and nuclear
      factor of activated T-cells (NFATc2). Dehydroepiandrosterone (DHEA) is a steroid
      hormone shown to reverse vascular remodeling in systemic vessels. Since STAT3 has
      been described as modulated by DHEA, we hypothesized that DHEA reverses human
      pulmonary hypertension by inhibiting Src/STAT3 constitutive activation. Using
      PASMCs isolated from patients with PAH (n = 3), we demonstrated that DHEA
      decreases both Src and STAT3 activation (Western blot and nuclear translocation
      assay), resulting in a significant reduction of Pim1, NFATc2
      expression/activation (quantitative RT-PCR and Western blot), as well as Survivin
      and upregulation of bone morphogenetic protein receptor 2 (BMPR2) and miR-204.
      Src/STAT3 axis inhibition by DHEA is associated with 1) mitochondrial membrane
      potential (tetramethylrhodamine methyl-ester perchlorate; n = 150; P < 0.05)
      depolarization increasing apoptosis by 25% (terminal deoxynucleotidyl transferase
      dUTP-mediated nick-end labeling; n = 150; P < 0.05); and 2) decreased
      intracellular Ca(2+) concentration (fluo-3 AM; n = 150; P < 0.05) and
      proliferation by 30% (PCNA). Finally, in vivo similarly to STAT3 inhibition DHEA
      improves experimental PAH (monocrotaline rats) by decreasing mean PA pressure and
      right ventricle hypertrophy. These effects were associated with the inhibition of
      Src, STAT3, Pim1, NFATc2, and Survivin and the upregulation of BMPR2 and miR-204.
      We demonstrated that DHEA reverses pulmonary hypertension in part by inhibiting
      the Src/STAT3.

PMID- 21890686
TI  - Metabolic stress in isolated mouse ventricular myocytes leads to remodeling of t
      tubules.
AB  - Cardiac ventricular myocytes possess an extensive t-tubular system that
      facilitates the propagation of membrane potential across the cell body. It is
      well established that ionic currents at the restricted t-tubular space may lead
      to significant changes in ion concentrations, which, in turn, may affect t
      tubular membrane potential. In this study, we used the whole cell patch-clamp
      technique to study accumulation and depletion of t-tubular potassium by measuring
      inward rectifier potassium tail currents (I(K1,tail)), and inward rectifier
      potassium current (I(K1)) "inactivation". At room temperatures and in the absence
      of Mg(2+) ions in pipette solution, the amplitude of I(K1,tail) measured ~10 min
      after the establishment of whole cell configuration was reduced by ~18%, but
      declined nearly twofold in the presence of 1 mM cyanide. At ~35 degrees C
      I(K1,tail) was essentially preserved in intact cells, but its amplitude declined
      by ~85% within 5 min of cell dialysis, even in the absence of cyanide.
      Intracellular Mg(2+) ions played protective role at all temperatures. Decline of
      I(K1,tail) was accompanied by characteristic changes in its kinetics, as well as
      by changes in the kinetics of I(K1) inactivation, a marker of depletion of t
      tubular K(+). The data point to remodeling of t tubules as the primary reason for
      the observed effects. Consistent with this, detubulation of myocytes using
      formamide-induced osmotic stress significantly reduced I(K1,tail), as well as the
      inactivation of inward I(K1). Overall, the data provide strong evidence that
      changes in t tubule volume/structure may occur on a short time scale in response
      to various types of stress.

PMID- 21890687
TI  - Sepiapterin enhances angiogenesis and functional recovery in mice after
      myocardial infarction.
AB  - Uncoupling of nitric oxide synthase (NOS) has been implicated in left ventricular
      (LV) remodeling and dysfunction after myocardial infarction (MI). We hypothesized
      that inducible NOS (iNOS) plays a crucial role in LV remodeling after MI,
      depending on its coupling status. MI was created in wild-type, iNOS-knockout
      (iNOS(-/-)), endothelial NOS-knockout (eNOS(-/-)), and neuronal NOS-knockout
      (nNOS(-/-)) mice. iNOS and nNOS expressions were increased after MI associated
      with an increase in nitrotyrosine formation. The area of myocardial fibrosis and
      LV end-diastolic volume and ejection fraction were more deteriorated in eNOS(-/-)
      mice compared with other genotypes of mice 4 wk after MI. The expression of GTP
      cyclohydrolase was reduced, and tetrahydrobiopterin (BH(4)) was depleted in the
      heart after MI. Oral administration of sepiapterin after MI increased
      dihydrobiopterin (BH(2)), BH(4), and BH(4)-to-BH(2) ratio in the infarcted but
      not sham-operated heart. The increase in BH(4)-to-BH(2) ratio was associated with
      inhibition of nitrotyrosine formation and an increase in nitrite plus nitrate.
      However, this inhibition of NOS uncoupling was blunted in iNOS(-/-) mice.
      Sepiapterin increased capillary density and prevented LV remodeling and
      dysfunction after MI in wild-type, eNOS(-/-), and nNOS(-/-) but not iNOS(-/-)
      mice. N(omega)-nitro-L-arginine methyl ester abrogated sepiapterin-induced
      increase in nitrite plus nitrate and angiogenesis and blocked the beneficial
      effects of sepiapterin on LV remodeling and function. These results suggest that
      sepiapterin enhances angiogenesis and functional recovery after MI by activating
      the salvage pathway for BH(4) synthesis and increasing bioavailable nitric oxide
      predominantly derived from iNOS.

PMID- 21890688
TI  - Nitric oxide formation by lymphatic bulb and valves is a major regulatory
      component of lymphatic pumping.
AB  - Microscopic lymphatics produce nitric oxide (NO) during contraction as flow shear
      activates the endothelial cells. The valve leaflets and bulbous valve housing
      contain a large amount of endothelial nitric oxide synthase (eNOS) due both to
      many endothelial cells and increased expression of eNOS. Direct NO measurements
      indicate the valve area has a 30-50% higher NO concentration ([NO]) than tubular
      regions although both regions generate equivalent relative increases in [NO] with
      each contraction. We hypothesize that 1) the greater eNOS and [NO] of the bulb
      region would have greater effects to lower pumping activity of the overall
      lymphatic than occurs in tubular regions and 2), the elevated [NO] in the bulb
      region may be because of high NO production in the valve leaflets that diffuses
      to the wall of the bulb. Measurement of [NO] with a micropipette inside the
      lymphatic bulb revealed the valve leaflets generate ~50% larger [NO] than the
      bulb wall in the in vivo rat mesenteric lymphatics. The valves add NO to the
      lymph that quickly diffuses to the bulb wall. Bradykinin locally released
      iontophoretically from a micropipette on both bulbs and tubes increased the [NO]
      in a dose-dependent manner up to ~50%, demonstrating agonist activation of the NO
      pathway. However, pumping output determined by contraction frequency and stroke
      volume decreased much more for the bulb than tubular areas in response to the
      bradykinin. In effect, NO generation by the bulb area and its valves limits the
      pumped flow of the total lymphatic by lowering frequency and stroke volume of
      individual contractions.

PMID- 21890689
TI  - Myocardial injury after ischemia-reperfusion in mice deficient in Akt2 is
      associated with increased cardiac macrophage density.
AB  - Akt2 protein kinase has been shown to promote cell migration and actin
      polymerization in several cell types, including macrophages. Because migrating
      macrophages constitute an important inflammatory response after myocardial
      ischemia, we determined cardiac macrophage expression after ischemia-reperfusion
      (I/R) injury and cryo-injury in mice lacking Akt2 (Akt2-KO). At 7 days post-I/R,
      Akt2-KO cardiac tissues showed an increase in immunohistochemical staining for
      macrophage markers (Galectin 3 and F4/80) compared with wild-type (WT) mice,
      indicating macrophage density was increased in the injured Akt2-KO myocardium.
      This change was time dependent because macrophage density was similar between WT
      and Akt2-KO myocardium at 3 days post-I/R, but by 7 and 14 days post-I/R,
      macrophage density was significantly increased in Akt2-KO myocardium.
      Concomitantly, infarct size was larger and cardiac function was reduced in Akt2
      KO mice subjected to I/R. However, when cryo-infarction produced similar infarct
      sizes in the anterior wall in both WT and Akt2-KO mice, macrophage density
      remained higher in Akt2-KO mouse myocardium, suggesting Akt2 regulates myocardial
      macrophage density independent of infarct size. Consistently, bone marrow from
      Akt2-KO mice enhanced myocardial macrophage density in both C57/B6 WT and Akt2-KO
      recipient mice. Finally, reciprocal ex-vivo coculturing of macrophages and
      cardiac myocytes showed that activated Akt2-KO peritoneal macrophages had reduced
      mobility and adhesion when compared with WT littermate controls. Thus, although
      Akt-2 KO mice did not affect the initial inflammation response after injury and
      Akt2 deficiency has been shown to impair cell migration or motility in
      macrophages, our data suggested a novel mechanism in which increasing retention
      of Akt2-KO macrophages resulted in increasing cardiac Akt2-KO macrophage density
      in the myocardial space.

PMID- 21890690
TI  - Mitochondrial autophagy by Bnip3 involves Drp1-mediated mitochondrial fission and
      recruitment of Parkin in cardiac myocytes.
AB  - The Bcl2/adenovirus E1B 19-kDa interacting protein 3 (Bnip3) is an atypical BH3
      only protein that is associated with mitochondrial dysfunction and cell death.
      Bnip3 is also a potent inducer of mitochondrial autophagy, and in this study we
      have investigated the mechanisms by which Bnip3 induces autophagy in cardiac
      myocytes. We found that Bnip3 induced mitochondrial translocation of dynamin
      related protein 1 (Drp1), a protein involved in mitochondrial fission in adult
      myocytes. Drp1-mediated mitochondrial fission correlated with increased
      autophagy, and inhibition of Drp1 reduced Bnip3-mediated autophagy.
      Overexpression of Drp1K38E, a dominant negative of Drp1, or mitofusin 1 prevented
      mitochondrial fission and autophagy by Bnip3. Also, inhibition of mitochondrial
      fission or autophagy resulted in increased death of myocytes overexpressing
      Bnip3. Moreover, Bnip3 promoted translocation of the E3 ubiquitin ligase Parkin
      to mitochondria, which was prevented in the presence of a Drp1 inhibitor.
      Interestingly, induction of autophagy by Bnip3 was reduced in Parkin-deficient
      myocytes. Thus our data suggest that induction of autophagy in response to Bnip3
      is a protective response activated by the cell that involves Drp1-mediated
      mitochondrial fission and recruitment of Parkin.

PMID- 21890691
TI  - Endothelial growth factor therapy improves preeclampsia-like manifestations in a
      murine model induced by overexpression of sVEGFR-1.
AB  - This study examines the effects of VEGF-121 therapy in an animal model of
      preeclampsia induced by overexpression of soluble VEGF receptor 1 (sVEGFR-1). At
      day 8 of gestation, CD-1 mice were implanted with subcutaneous osmotic pumps
      containing either VEGF-121 or vehicle and fitted with telemetric blood pressure
      (BP) catheters for continuous BP monitoring (days 8-18 of gestation). On day 9,
      the animals in the VEGF-121 group were randomly allocated for injection with
      adenovirus carrying sVEGFR-1 or the murine immunoglobulin G2alpha Fc fragment
      (mFc) as virus control (Adv-sVEGFR-1; Adv-mFc). Animals in the vehicle group were
      injected with Adv-sVEGFR-1. On day 18, mice were euthanized, placentas and pups
      weighted, carotid arteries isolated, and their responses studied in vitro using a
      wire myograph for isometric tension recording. In mice overexpressing sVEGFR-1,
      treatment with VEGF-121 significantly reduced BP from days 10 to 18 of gestation
      compared with that of vehicle. VEGF-sVEGFR-1 animals had significantly higher
      vasorelaxant response to sodium nitroprusside and significantly lower contractile
      response to the thromboxane agonist (U-46619) compared with that of the vehicle
      sVEGFR-1 mice. Phenylephrine and acetylcholine responses did not significantly
      vary between the VEGF-sVEGFR-1 and the vehicle-sVEGFR-1 mice. Average pup weight
      was significantly lower in the vehicle-sVEGFR-1 group compared with the VEGF
      sVEGFR-1 and VEGF-mFc groups. In conclusion, VEGF-121 therapy attenuates vascular
      dysfunction and diminishes intrauterine growth abnormality in an animal model of
      preeclampsia induced by overexpression of sVEGFR-1. Modulation of VEGF pathway
      turns into a promising therapeutic approach of preeclampsia.

PMID- 21890692
TI  - Nuclear GPCRs in cardiomyocytes: an insider's view of beta-adrenergic receptor
      signaling.
AB  - In recent years, we have come to appreciate the complexity of G protein-coupled
      receptor signaling in general and beta-adrenergic receptor (beta-AR) signaling in
      particular. Starting originally from three beta-AR subtypes expressed in
      cardiomyocytes with relatively simple, linear signaling cascades, it is now clear
      that there are large receptor-based networks which provide a rich and diverse set
      of responses depending on their complement of signaling partners and the
      physiological state. More recently, it has become clear that subcellular
      localization of these signaling complexes also enriches the diversity of
      phenotypic outcomes. Here, we review our understanding of the signaling
      repertoire controlled by nuclear beta-AR subtypes as well our understanding of
      the novel roles for G proteins themselves in the nucleus, with a special focus,
      where possible, on their effects in cardiomyocytes. Finally, we discuss the
      potential pathological implications of alterations in nuclear beta-AR signaling.

PMID- 21890693
TI  - Splanchnic sympathetic nerves in the development of mild DOCA-salt hypertension.
AB  - We previously reported that mild deoxycorticosterone acetate (DOCA)-salt
      hypertension develops in the absence of generalized sympathoexcitation. However,
      sympathetic nervous system activity (SNA) is regionally heterogeneous, so we
      began to investigate the role of sympathetic nerves to specific regions. Our
      first study on that possibility revealed no contribution of renal nerves to
      hypertension development. The splanchnic sympathetic nerves are implicated in
      blood pressure (BP) regulation because splanchnic denervation effectively lowers
      BP in human hypertension. Here we tested the hypothesis that splanchnic SNA
      contributes to the development of mild DOCA-salt hypertension. Splanchnic
      denervation was achieved by celiac ganglionectomy (CGX) in one group of rats
      while another group underwent sham surgery (SHAM-GX). After DOCA treatment (50
      mg/kg) in rats with both kidneys intact, CGX rats exhibited a significantly
      attenuated increase in BP compared with SHAM-GX rats (15.6 +/- 2.2 vs. 25.6 +/-
      2.2 mmHg, day 28 after DOCA treatment). In other rats, whole body norepinephrine
      (NE) spillover, measured to determine if CGX attenuated hypertension development
      by reducing global SNA, was not found to be different between SHAM-GX and CGX
      rats. In a third group, nonhepatic splanchnic NE spillover was measured as an
      index of splanchnic SNA, but this was not different between SHAM (non-DOCA
      treated) and DOCA rats during hypertension development. In a final group, CGX
      effectively abolished nonhepatic splanchnic NE spillover. These data suggest that
      an intact splanchnic innervation is necessary for mild DOCA-salt hypertension
      development but not increased splanchnic SNA or NE release. Increased splanchnic
      vascular reactivity to NE during DOCA-salt treatment is one possible explanation.

PMID- 21890695
TI  - The Rho kinase inhibitor Y-27632 increases erythrocyte deformability and low
      oxygen tension-induced ATP release.
AB  - Low oxygen (O(2)) tension and mechanical deformation are stimuli for ATP release
      from erythrocytes. It has been shown previously that rabbit erythrocytes made
      less deformable with diamide, a thiol cross-linking agent, release less ATP in
      response to low O(2) tension, suggesting a link between these two stimuli. In
      nonerythroid cells, activation of the Rho/Rho kinase signaling pathway has been
      reported to decrease cell deformability by altering Rho kinase-dependent
      cytoskeleton-protein interactions. We investigated the hypothesis that the Rho
      kinase inhibitor Y-27632 would increase erythrocyte deformability and thereby
      increase low O(2) tension-induced ATP release from erythrocytes. Here we show
      that Y-27632 (1 MUM) increases erythrocyte deformability (5%) and increases low
      O(2) tension-induced ATP release (203%) from healthy human erythrocytes. In
      addition, we found that, when erythrocytes were made less deformable by
      incubation with diamide (100 MUM), Y-27632 restored both deformability and low
      O(2) tension-induced ATP release to levels similar to those measured in the
      absence of diamide. These findings suggest that the Rho kinase inhibitor Y-27632
      is able to reverse the diamide-induced decrease in erythrocyte deformability and
      rescue low O(2) tension-induced ATP release. These results further support a link
      between erythrocyte deformability and ATP release in response to low O(2)
      tension.

PMID- 21890696
TI  - The impact of a school garden and cooking program on boys' and girls' fruit and
      vegetable preferences, taste rating, and intake.
AB  - The aim of this study was to examine gender differences in the impact of a school
      garden and nutrition curriculum on fruit and vegetable intake, willingness to
      taste, and taste ratings in 127 children (11 to 12 years, 54% boys) in regional
      New South Wales, Australia. Classes were assigned to wait-list control, nutrition
      education only (NE), or nutrition education plus garden (NE + G) groups. Carrot
      taste rating was the only vegetable for which there was a significant gender
      difference, with girls rating it more highly (p = .04). There were no significant
      gender differences in fruit and vegetable consumption or willingness to taste
      scores for any other vegetables. There was a group effect (p < .001) for overall
      willingness to taste, overall taste rating, and the taste rating of pea and
      broccoli (p < .001), tomato (p = .03), and lettuce (p = .02). In the post hoc
      analysis by gender, both boys and girls in NE + G and NE groups were more willing
      to taste vegetables compared with control boys and girls postintervention (p <
      .001, p = .02). Boys in the NE + G group were more willing to taste all
      vegetables overall compared with NE boys at posttest (p = .05) and this
      approached significance for girls (p = .07). For overall tasting scores, a group
      effect was seen in girls only (p = .05). No significant treatment-time effect was
      found for vegetable intake in either gender. Further research is needed to
      examine whether a school garden, with or without school curriculum components,
      can be used to optimize fruit and vegetable intakes, particularly in boys.

PMID- 21890694
TI  - High purity human-induced pluripotent stem cell-derived cardiomyocytes:
      electrophysiological properties of action potentials and ionic currents.
AB  - Human-induced pluripotent stem cells (hiPSCs) can differentiate into functional
      cardiomyocytes; however, the electrophysiological properties of hiPSC-derived
      cardiomyocytes have yet to be fully characterized. We performed detailed
      electrophysiological characterization of highly pure hiPSC-derived
      cardiomyocytes. Action potentials (APs) were recorded from spontaneously beating
      cardiomyocytes using a perforated patch method and had atrial-, nodal-, and
      ventricular-like properties. Ventricular-like APs were more common and had
      maximum diastolic potentials close to those of human cardiac myocytes, AP
      durations were within the range of the normal human electrocardiographic QT
      interval, and APs showed expected sensitivity to multiple drugs (tetrodotoxin,
      nifedipine, and E4031). Early afterdepolarizations (EADs) were induced with E4031
      and were bradycardia dependent, and EAD peak voltage varied inversely with the
      EAD take-off potential. Gating properties of seven ionic currents were studied
      including sodium (I(Na)), L-type calcium (I(Ca)), hyperpolarization-activated
      pacemaker (I(f)), transient outward potassium (I(to)), inward rectifier potassium
      (I(K1)), and the rapidly and slowly activating components of delayed rectifier
      potassium (I(Kr) and I(Ks), respectively) current. The high purity and large cell
      numbers also enabled automated patch-clamp analysis. We conclude that these hiPSC
      derived cardiomyocytes have ionic currents and channel gating properties
      underlying their APs and EADs that are quantitatively similar to those reported
      for human cardiac myocytes. These hiPSC-derived cardiomyocytes have the added
      advantage that they can be used in high-throughput assays, and they have the
      potential to impact multiple areas of cardiovascular research and therapeutic
      applications.

PMID- 21890697
TI  - Role of ArgP (IciA) in lysine-mediated repression in Escherichia coli.
AB  - Initially identified as an inhibitor of oriC-initiated DNA replication in vitro,
      the ArgP or IciA protein of Escherichia coli has subsequently been described as a
      nucleoid-associated protein and also as a transcriptional regulator of genes
      involved in DNA replication (dnaA and nrdA) and amino acid metabolism (argO,
      dapB, and gdhA [the last in Klebsiella pneumoniae]). ArgP mediates lysine (Lys)
      repression of argO, dapB, and gdhA in vivo, for which two alternative mechanisms
      have been identified: at the dapB and gdhA regulatory regions, ArgP binding is
      reduced upon the addition of Lys, whereas at argO, RNA polymerase is trapped at
      the step of promoter clearance by Lys-bound ArgP. In this study, we have examined
      promoter-lac fusions in strains that were argP(+) or DeltaargP or that were
      carrying dominant argP mutations in order to identify several new genes that are
      ArgP-regulated in vivo, including lysP, lysC, lysA, dapD, and asd (in addition to
      argO, dapB, and gdhA). All were repressed upon Lys supplementation, and in vitro
      studies demonstrated that ArgP binds to the corresponding regulatory regions in a
      Lys-sensitive manner (with the exception of argO, whose binding to ArgP was Lys
      insensitive). Neither dnaA nor nrdA was ArgP regulated in vivo, although their
      regulatory regions exhibited low-affinity binding to ArgP. Our results suggest
      that ArgP is a transcriptional regulator for Lys repression of genes in E. coli
      but that it is noncanonical in that it also exhibits low-affinity binding,
      without apparent direct regulatory effect, to a number of additional sites in the
      genome.

PMID- 21890698
TI  - Modulation of substrate efflux in bacterial small multidrug resistance proteins
      by mutations at the dimer interface.
AB  - Bacteria evade the effects of cytotoxic compounds through the efflux activity of
      membrane-bound transporters such as the small multidrug resistance (SMR)
      proteins. Consisting typically of ca. 110 residues with four transmembrane (TM)
      alpha-helices, crystallographic studies have shown that TM helix 1 (TM1) through
      TM helix 3 (TM3) of each monomer create a substrate binding "pocket" within the
      membrane bilayer, while a TM4-TM4 interaction accounts for the primary dimer
      formation. Previous work from our lab has characterized a highly conserved small
      residue heptad motif in the Halobacterium salinarum transporter Hsmr as
      (90)GLXLIXXGV(98) that lies along the TM4-TM4 dimer interface of SMR proteins as
      required for function. Focusing on conserved positions 91, 93, 94, and 98, we
      substituted the naturally occurring Hsmr residue for Ala, Phe, Ile, Leu, Met, and
      Val at each position in the Hsmr TM4-TM4 interface. Large-residue replacements
      were studied for their ability to dimerize on SDS-polyacrylamide gels, to bind
      the cytotoxic compound ethidium bromide, and to confer resistance by efflux.
      Although the relative activity of mutants did not correlate with dimer strength
      for all mutants, all functional mutants lay within 10% of dimerization relative
      to the wild type (WT), suggesting that the optimal dimer strength at TM4 is
      required for proper efflux. Furthermore, nonfunctional substitutions at the
      center of the dimerization interface that do not alter dimer strength suggest a
      dynamic TM4-TM4 "pivot point" that responds to the efflux requirements of
      different substrates. This functionally critical region represents a potential
      target for inhibiting the ability of bacteria to evade the effects of cytotoxic
      compounds.

PMID- 21890699
TI  - Phage-borne factors and host LexA regulate the lytic switch in phage GIL01.
AB  - The Bacillus thuringiensis temperate phage GIL01 does not integrate into the host
      chromosome but exists stably as an independent linear replicon within the cell.
      Similar to that of the lambdoid prophages, the lytic cycle of GIL01 is induced as
      part of the cellular SOS response to DNA damage. However, no CI-like maintenance
      repressor has been detected in the phage genome, suggesting that GIL01 uses a
      novel mechanism to maintain lysogeny. To gain insights into the GIL01 regulatory
      circuit, we isolated and characterized a set of 17 clear plaque (cp) mutants that
      are unable to lysogenize. Two phage-encoded proteins, gp1 and gp7, are required
      for stable lysogen formation. Analysis of cp mutants also identified a 14-bp
      palindromic dinBox1 sequence within the P1-P2 promoter region that resembles the
      known LexA-binding site of Gram-positive bacteria. Mutations at conserved
      positions in dinBox1 result in a cp phenotype. Genomic analysis identified a
      total of three dinBox sites within GIL01 promoter regions. To investigate the
      possibility that the host LexA regulates GIL01, phage induction was measured in a
      host carrying a noncleavable lexA (Ind(-)) mutation. GIL01 formed stable lysogens
      in this host, but lytic growth could not be induced by treatment with mitomycin
      C. Also, mitomycin C induced beta-galactosidase expression from GIL01-lacZ
      promoter fusions, and induction was similarly blocked in the lexA (Ind(-)) mutant
      host. These data support a model in which host LexA binds to dinBox sequences in
      GIL01, repressing phage gene expression during lysogeny and providing the switch
      necessary to enter lytic development.

PMID- 21890700
TI  - The surfactant of Legionella pneumophila Is secreted in a TolC-dependent manner
      and is antagonistic toward other Legionella species.
AB  - When Legionella pneumophila grows on agar plates, it secretes a surfactant that
      promotes flagellum- and pilus-independent "sliding" motility. We isolated three
      mutants that were defective for surfactant. The first two had mutations in genes
      predicted to encode cytoplasmic enzymes involved in lipid metabolism. These genes
      mapped to two adjacent operons that we designated bbcABCDEF and bbcGHIJK.
      Backcrossing and complementation confirmed the importance of the bbc genes and
      suggested that the Legionella surfactant is lipid containing. The third mutant
      had an insertion in tolC. TolC is the outer membrane part of various trimolecular
      complexes involved in multidrug efflux and type I protein secretion.
      Complementation of the tolC mutant restored sliding motility. Mutants defective
      for an inner membrane partner of TolC also lacked a surfactant, confirming that
      TolC promotes surfactant secretion. L. pneumophila (lspF) mutants lacking type II
      protein secretion (T2S) are also impaired for a surfactant. When the tolC and
      lspF mutants were grown next to each other, the lsp mutant secreted surfactant,
      suggesting that TolC and T2S conjoin to mediate surfactant secretion, with one
      being the conduit for surfactant export and the other the exporter of a molecule
      that is required for induction or maturation of surfactant synthesis/secretion.
      Although the surfactant was not required for the extracellular growth,
      intracellular infection, and intrapulmonary survival of L. pneumophila, it
      exhibited antimicrobial activity toward seven other species of Legionella but not
      toward various non-Legionella species. These data suggest that the surfactant
      provides L. pneumophila with a selective advantage over other legionellae in the
      natural environment.

PMID- 21890701
TI  - Adjusting the spokes of the flagellar motor with the DNA-binding protein H-NS.
AB  - The H-NS protein of bacteria is a global regulator that stimulates transcription
      of flagellar genes and that also acts directly to modulate flagellar motor
      function. H-NS is known to bind FliG, a protein of the rotor that interacts with
      the stator and is directly involved in rotation of the motor. Here, we find that
      H-NS, well known for its ability to organize DNA, acts in the flagellar motor to
      organize protein subunits in the rotor. It binds to a middle domain of FliG that
      bridges the core parts of the rotor and parts nearer the edge that interact with
      the stator. In the absence of H-NS the organization of FliG subunits is
      disrupted, whereas overexpression of H-NS enhances FliG organization as monitored
      by targeted disulfide cross-linking, alters the disposition of a helix joining
      the middle and C-terminal domains of FliG, and enhances motor performance under
      conditions requiring a strengthened rotor-stator interface. The H-NS homolog StpA
      was also shown to bind FliG and to act similarly, though less effectively, in
      organizing FliG. The motility-enhancing effects of H-NS contrast with those of
      the recently characterized motility inhibitor YcgR. The present findings provide
      an integrated, structurally grounded framework for understanding the roughly
      opposing effects of these motility regulators.

PMID- 21890702
TI  - Genetic analysis of SCO2997, encoding a TagF homologue, indicates a role for wall
      teichoic acids in sporulation of Streptomyces coelicolor A3(2).
AB  - Streptomyces coelicolor contains two gene clusters putatively involved in wall
      teichoic acid biosynthesis. Inactivation of the tagF homologue SCO2997 or
      SCO2584, a component of the Streptomyces spore wall synthesizing complex,
      affected sporulation. The mutant phenotypes resembled those of mre mutants,
      suggesting a function of wall teichoic acids in the differentiation of
      Streptomyces.

PMID- 21890703
TI  - An ATP-grasp ligase involved in the last biosynthetic step of the
      iminomycosporine shinorine in Nostoc punctiforme ATCC 29133.
AB  - We investigated the genetic basis for mycosporine sunscreen biosynthesis by the
      cyanobacterium Nostoc punctiforme ATCC 29133. Heterologous expression in
      Escherichia coli of three contiguous N. punctiforme genes (NpR5600, NpR5599, and
      NpR5598, here named mysA, mysB, and mysC, respectively) led to the production of
      mycosporine-glycine, an oxomycosporine. Additional expression of gene NpF5597
      (mysD) led to the conversion of mycosporine-glycine into iminomycosporines
      (preferentially shinorine but also others like mycosporine-2-glycine and porphyra
      334). This represents a new mode of enzymatic synthesis for iminomycosporines,
      one that differs in genetic origin, mechanism, and apparent substrate specificity
      from that known in Anabaena variabilis ATCC 29413. These results add to the
      emerging profile of the protein family of ATP-dependent ligases, to which the
      mysC product belongs, as important condensation enzymes in microbial secondary
      metabolism.

PMID- 21890704
TI  - Mutations in genes patA and patL of Anabaena sp. strain PCC 7120 result in
      similar phenotypes, and the proteins encoded by those genes may interact.
AB  - PatA resembles a response regulator protein with a defective DNA-binding domain,
      and PatL (All3305) is a pentapeptide repeat protein. A yeast two-hybrid library
      identified PatL as a protein with which PatA may interact. Heterocysts of patA
      and patL Anabaena sp. form nearly exclusively terminally in long filaments,
      further linking the genes.

PMID- 21890705
TI  - The opportunistic pathogen Serratia marcescens utilizes type VI secretion to
      target bacterial competitors.
AB  - The type VI secretion system (T6SS) is the most recently described and least
      understood of the protein secretion systems of Gram-negative bacteria. It is
      widely distributed and has been implicated in the virulence of various pathogens,
      but its mechanism and exact mode of action remain to be defined. Additionally
      there have been several very recent reports that some T6SSs can target bacteria
      rather than eukaryotic cells. Serratia marcescens is an opportunistic enteric
      pathogen, a class of bacteria responsible for a significant proportion of
      hospital-acquired infections. We describe the identification of a functional T6SS
      in S. marcescens strain Db10, the first report of type VI secretion by an
      opportunist enteric bacterium. The T6SS of S. marcescens Db10 is active, with
      secretion of Hcp to the culture medium readily detected, and is expressed
      constitutively under normal growth conditions from a large transcriptional unit.
      Expression of the T6SS genes did not appear to be dependent on the integrity of
      the T6SS. The S. marcescens Db10 T6SS is not required for virulence in three
      nonmammalian virulence models. It does, however, exhibit dramatic antibacterial
      killing activity against several other bacterial species and is required for S.
      marcescens to persist in a mixed culture with another opportunist pathogen,
      Enterobacter cloacae. Importantly, this antibacterial killing activity is highly
      strain specific, with the S. marcescens Db10 T6SS being highly effective against
      another strain of S. marcescens with a very similar and active T6SS. We conclude
      that type VI secretion plays a crucial role in the competitiveness, and thus
      indirectly the virulence, of S. marcescens and other opportunistic bacterial
      pathogens.

PMID- 21890706
TI  - Are United States and Canadian cancer screening rates consistent with guideline
      information regarding the age of screening initiation?
AB  - OBJECTIVE: To understand whether US and Canadian breast, colorectal and prostate
      cancer screening test utilization is consistent with US and Canadian cancer
      screening guideline information with respect to the age of screening initiation.
      DESIGN: Cross-sectional, regression discontinuity. SETTING: Canada and the US.
      PARTICIPANTS: Canadian and American women of ages 30-60 and men of ages 40-60.
      INTERVENTIONS: None. Main Outcomes Measures Mammography, prostate-specific
      antigen (PSA) and colorectal cancer test use within the past 2 years. METHODS: We
      identify US and Canadian compliance with age screening information in a novel
      manner, by comparing test utilization rates of individuals who are immediately on
      either side of the guideline recommended initiation ages. RESULTS: US mammography
      utilization within the last 2 years increased from 33% at age 39 to 48% at age 40
      and 60% at age 41. US colorectal cancer test utilization, within the last 2
      years, increased from 15% at age 49 to 18% at age 50 and 28% at age 51. US PSA
      utilization within the last 2 years increased from 37% at age 49 to 44% at age 50
      and 54% at age 51. In Canada, mammography utilization within the last 2 years
      increased from 47% at age 49 to 57% at age 50 and 66% at age 51. CONCLUSION:
      American and Canadian cancer screening utilization is generally consistent with
      each country's guideline recommendations regarding age. US and Canadian
      differences in screening due to guidelines can potentially explain cross-country
      differences in breast cancer mortality and affect interpretation of international
      comparisons of cancer statistics.

PMID- 21890707
TI  - Nitric oxide, nitrate reductase and UV-B tolerance.

PMID- 21890708
TI  - Profile of microRNAs differentially produced in hearts from patients with
      hypertrophic cardiomyopathy and sarcomeric mutations.

PMID- 21890709
TI  - Registered nurses integrate traditional Chinese medicine into the triage process.
AB  - People in the United States often consult registered nurses (nurses) for advice
      when they want to explore alternatives to Western medicine, such as traditional
      Chinese medicine (TCM). Nurses find themselves confronting dilemmas when they are
      caught between these radically different worlds of medical cultures and thinking.
      Twenty Minnesota nurses were interviewed to learn how they integrate TCM into
      their triage process. Symbolic interactionism was the research framework used,
      and mixed coding methods facilitated data analysis. Several sociological theories
      explain the findings. The major finding is that nurses use a four-step triage
      process that begins from the Western medical perspective and includes
      consideration of TCM use. Nurses' recommendations are influenced by their
      situational roles and relationships, and by the cues they read from the person
      who is asking their advice. The results point to nurses being natural
      disseminators of TCM information and education in their resource role for others
      making health care decisions.

PMID- 21890710
TI  - Living positively: the experiences of Thai women living with HIV/AIDS in central
      Thailand.
AB  - Living with an incurable illness such as HIV/AIDS is a stressful experience.
      However, many HIV-positive individuals are able to maintain their emotional well
      being. This begs the question of what strategies these individuals employ to
      allow them to do so. In this article, we examine how Thai women living with
      HIV/AIDS learned about their health status, what feelings they had, and how they
      dealt with the illness. In-depth interviews were conducted with 26 women in
      central Thailand. The women adopted several strategies to deal with their HIV
      status, including taking care of themselves, accepting their own faith,
      disclosing their HIV status to family, and joining AIDS support groups. These
      strategies can be situated within the "living positively" discourse, which helped
      to create a sense of optimism to combat the HIV epidemic among the women.
      Additionally, the acceptance of their HIV status played an essential role in the
      meaning-making process because it assisted the women in sustaining the
      equilibrium of their emotional well-being.

PMID- 21890711
TI  - Parental cancer: catalyst for positive growth and change.
AB  - Cancer is a disease that affects the entire family, with each member having
      unique psychological needs. To date, there has been limited research into the
      effect of parental cancer on adult children. Furthermore, existing research has
      largely overlooked the possibility of positive psychological growth in the adult
      offspring of cancer patients. To investigate the perceived benefits arising from
      parental cancer, 11 interviews were undertaken with adults whose parents had been
      diagnosed with cancer, to discuss their experiences of their parent's illness,
      and their evaluation of both the positive and negative changes that had arisen.
      All participants were able to identify positive outcomes in direct response to
      their parent's cancer. Frequently suggested changes included improved
      relationships with their sick parent, an increased emphasis on family, revised
      life priorities, and personal development. The implications of these findings,
      their link to posttraumatic growth theory, and avenues for future research are
      discussed.

PMID- 21890712
TI  - "This is the best fatal illness that you can have": contrasting and comparing the
      experiences of parenting youth with cystic fibrosis and congenital heart disease.
AB  - Despite the important instrumental and emotional role that parents play in the
      lives of children with cystic fibrosis (CF) and congenital heart disease (CHD),
      qualitative researchers have not examined the similarities and differences
      between caregivers' experiences. Informed by thematic analysis, in this
      qualitative study I explored what it is like to care for a child with a chronic
      illness from the perspective of CF and CHD parents at a children's hospital in
      Canada. Pediatric caregiver stress was qualitatively different between CF and CHD
      parents, whereas temporal dilemmas were unique sources of stress for CF parents
      only. To alleviate stress, all parents drew on a three-way, interrelated process
      to comprehend their child's illness and acquire perspective. By opening up the
      social worlds of parents, I illuminate important similarities and differences in
      the caregiving experience of parents of youth with CF and CHD, and offer novel
      contributions to the literature.

PMID- 21890713
TI  - Discourses of influence and autonomy in physicians' accounts of treatment
      decision making for depression.
AB  - Models of patient-physician decision making are typically framed on a continuum
      of discourses and practices ranging from patient autonomy to physician
      paternalism, with the middle ground being occupied by terms such as shared
      decision making. Critiques of these models center on the gulf between these
      idealized models and actual practice and on how context influences decision
      making practices. In this article I focus on how 11 Canadian family physicians
      talked about patient-physician decision making in interviews about their
      diagnostic and treatment practices for depression. I adopt a discursive approach
      to analyzing extracts from these interviews, and show how these physicians
      constructed themselves as engaging in acts of professional judgment and
      persuasion, and patients as having the final say in decision making about
      treatment for depression. I argue that whether the intertwining of discourses of
      physician influence and patient autonomy is understood as a balance of power
      between physicians and patients is an open question.

PMID- 21890714
TI  - Living with arthritis: using self-management of valued activities to promote
      health.
AB  - In this article, we explore how adults with arthritis use self-care strategies in
      their valued leisure activities, and variations in use based on their access to
      environmental resources. We conducted six focus groups (N = 34) with adults aged
      55 and older with a diagnosis of arthritis. Adults living in residential
      communities were recruited, with 31% of the sample residing in subsidized
      housing. Focus group transcripts were analyzed using content analysis based on
      themes of selective optimization with compensation. We found some differences in
      strategy use between the resource-rich and resource-poor participants. Adults
      highlighted the value of their leisure activities and the importance of leisure
      in maintaining their health and well-being. Our findings point to the need to
      incorporate leisure education into interventions and programs targeting adults
      with arthritis.

PMID- 21890715
TI  - A working relationship model that reduces homelessness among people with mental
      illness.
AB  - We applied grounded theory methodology to generate a working relationship model
      that influences motivation for stable housing among homeless people with serious
      mental illness, to understand the role of a working relationship in critical
      service transitions. We focused on practitioners' perspectives and practices in
      Critical Time Intervention (CTI), a community intervention aimed to reduce
      homelessness through providing support during the transition from institutional
      to community living. We found a working relationship that highlighted
      "nonauthoritative" and "humanistic" features. Workers respected client autonomy
      and maintained flexibility in the format of client contact and service
      activities. They used practice strategies including following client leads and
      informal relating approaches to facilitate the development of client trust. The
      trusting relationship enhanced client interest in obtaining housing and the
      commitment to the transformation crucial for retaining housing. We discuss the
      significance of the relationship and ethical considerations of relationship
      building activities in community mental health practices.

PMID- 21890716
TI  - Parents' emotional and social experiences of caring for a child through cleft
      treatment.
AB  - Little is known about the experiences of parents caring for a child through long
      term treatment for cleft lip and/or cleft palate. We conducted in-depth
      interviews with 35 parents with children between the ages of 20 weeks and 21
      years to explore experiences across the treatment program. We analyzed the data
      using a constructivist grounded theory approach and present in detail in this
      article one subcategory from the analysis: managing emotions. Throughout
      childhood and adolescence, parents experienced conflicting emotions about their
      child's impairment, uncertainty about cleft treatment, and stigmatizing
      attitudes. Although parents attempted to manage emotional tensions by pursuing
      cleft treatments, the interventions could themselves be a source of conflict for
      them. We suggest that routine assessment of parents' emotional and social well
      being should be included in cleft treatment programs, and access to psychosocial
      support made available.

PMID- 21890717
TI  - Perceived competency and resolution of homelessness among women with substance
      abuse problems.
AB  - Using a metasynthesis approach, our aim was to articulate new insights relating
      to the most efficient and effective means of helping homeless women with
      substance abuse problems to enhance their well-being and become more stably
      housed. Distorted perceptions of competency, which are shaped by dysfunctional
      relationships and mental health problems, make it challenging for women with
      substance abuse problems to resolve homelessness. Women with particularly low or
      high levels of perceived competency tend to grapple with challenges related to
      structure and control, trust, and hopelessness. Therapeutic strategies for
      approaching these women include careful assessment, caring, personalized
      structure and control, development of interpersonal trust, instillation of hope,
      and the targeted use of psychotherapeutic agents and counseling. Framing care for
      homeless women within the context of perceived competency offers a new way of
      understanding their plight and shaping interventions to more expeditiously move
      them toward healthy and stable lives.

PMID- 21890718
TI  - Establishing therapeutic relationships with vulnerable and potentially
      stigmatized clients.
AB  - Grounded theory was employed to elucidate how public health nurses (PHNs) develop
      therapeutic relationships with vulnerable and potentially stigmatized clients,
      specifically, single mothers living in low-income situations. We named the
      emerging theoretical model Targeting Essence: Pragmatic Variation of the
      Therapeutic Relationship, after discovering that although PHNs strove to achieve
      relational goals, their attention was primarily focused on the goal of
      ascertaining concerns foremost on the hearts and minds of mothers, and that PHNs
      had to accomplish these goals within short practice timeframes. The study's
      focused context elicited a nuanced explanation of the dynamic relationship
      building process derived from subjective relationship experiences of PHNs and
      single mothers living in low-income situations. We believe Targeting Essence will
      serve as an effectual relationship-building model, enabling PHNs to know
      essentially what mothers want and need, and enabling mothers to know essentially
      that their PHN can be trusted not to render judgment.

PMID- 21890719
TI  - Social networks of substance users with HIV infection: application of the Norbeck
      Social Support Scale.
AB  - The role of social support networks in medication adherence among HIV-infected
      substance users remains understudied. In this secondary data analysis, the
      authors sought to determine the relationship between social support networks and
      antiretroviral adherence among HIV-infected substance abusers receiving
      methadone. They analyzed data collected in a 24-week study of 76 methadone
      maintained, HIV-infected substance abusers randomized to directly observed
      antiretroviral therapy or treatment as usual. The authors used logistic
      regression to examine the relationship between social support networks and self
      reported antiretroviral adherence. Their results showed that study participants
      had an average of 1.36 social network members (SD = 1.4); 34% of participants had
      at least one drug user and 25% had at least one HIV-infected person in their
      network. The presence of network drug users and HIV-infected network members was
      associated with less antiretroviral medication adherence (p < .05). The authors
      conclude that both social network density and characteristics of network members
      have implications for medication adherence.

PMID- 21890720
TI  - Arenimonas daejeonensis sp. nov., isolated from compost.
AB  - A Gram-negative, aerobic, motile and rod-shaped bacterium, designated strain T7
      07(T), was isolated from compost in Daejeon, Korea. Phylogenetic analysis based
      on 16S rRNA gene sequencing showed that strain T7-07(T) had 99.0% gene sequence
      similarity with Arenimonas malthae KACC 14618(T) and 94.7-95.9% with other
      recognized species of the genus Arenimonas. Cells formed creamy white to
      yellowish colonies on R2A agar and contained Q-8 as the predominant ubiquinone,
      C(15:0) iso, C(16:0) iso, C(17:1) iso omega9c and C(11:0) iso 3-OH as the major
      fatty acids, and diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylglycerol, phosphatidylmethylethanolamine and an unknown aminolipid as
      the major polar lipids. The DNA G+C content of strain T7-07(T) was 68.3 mol%. DNA
      DNA reassociation experiments between T7-07(T) and Arenimonas malthae KACC
      14618(T) resulted in a mean relatedness value of 22.2%. Combined genotypic and
      phenotypic data supported the conclusion that the strain T7-07(T) represents a
      novel species, for which the name Arenimonas daejeonensis sp. nov. is proposed.
      The type strain is T7-07(T) (=KCTC 12667(T)=DSM 18060(T)).

PMID- 21890721
TI  - Promicromonospora endophytica sp. nov., an endophytic actinobacterium isolated
      from the root of an Australian native Grey Box tree.
AB  - A novel aerobic actinobacterium, strain EUM 273(T), was isolated from the root of
      a Grey Box tree (Eucalyptus microcarpa Maiden). Cells were Gram-staining-positive
      with well-developed substrate mycelia which were non-motile and rod-like, with
      coccoid elements. Phylogenetic evaluation based on 16S rRNA gene sequence
      analysis placed the isolate as a member of the family Promicromonosporaceae that
      was most closely related to Promicromonospora xylanilytica YIM 61515(T) (98.2%)
      and Promicromonospora vindobonensis V45(T) (98%). Chemotaxonomic data including
      cell wall components, major menaquinone and major fatty acids confirmed the
      affiliation of strain EUM 273(T) to the genus Promicromonospora. The results of
      the phylogenetic analysis, including physiological and biochemical studies in
      combination with DNA-DNA hybridization, allowed the genotypic and phenotypic
      differentiation of strain EUM 273(T) from the closest related species with
      validly published names. The name proposed for the novel species is
      Promicromonospora endophytica sp. nov. The type strain is EUM 273(T) (=DSM
      23716(T)=NRRL B-24816(T)).

PMID- 21890722
TI  - Emended description of the genus Methylophaga Janvier et al. 1985.
AB  - The genus Methylophaga Janvier et al. 1985 comprises eight species with validly
      published names at the time of writing. The original description of the genus was
      published over 26 years ago and was based on only two species, namely
      Methylophaga marina and Methylophaga thalassica - as such, the description of the
      genus requires updating to take into account the other six known species. Based
      on literature concerning the eight species of Methylophaga published over the
      last 26 years, an emended description of the genus is presented, taking into
      account properties of all members of the species with validly published names.

PMID- 21890724
TI  - Shewanella dokdonensis sp. nov., isolated from seawater.
AB  - A novel bacterial strain, designated UDC329(T), was isolated from a sample of
      seawater collected at Dong-do, on the coast of Dokdo Island, in the East Sea of
      the Republic of Korea. The Gram-staining-negative, motile, facultatively
      anaerobic, non-spore-forming rods of the strain developed into dark orange-yellow
      colonies. The strain grew optimally between 25 and 30  degrees C, with 1% (w/v)
      NaCl and at pH 7. It grew in the absence of NaCl, but not with NaCl at >7% (w/v).
      The predominant menaquinone was MK-7, the predominant ubiquinones were Q-7 and Q
      8, and the major fatty acids were iso-C(15:0) (33.52%) and C(17:1)omega8c
      (11.73%). The genomic DNA G+C content of strain UDC329(T) was 50.2 mol%. In
      phylogenetic analyses based on 16S rRNA and gyrB gene sequences, strain UDC329(T)
      was grouped with members of the genus Shewanella and appeared most closely
      related to Shewanella fodinae JC15(T) (97.9% 16S rRNA gene sequence similarity),
      Shewanella indica KJW27(T) (95.0%), Shewanella algae ATCC 51192(T) (94.8%),
      Shewanella haliotis DW01(T) (94.5%) and Shewanella chilikensis JC5(T) (93.9%).
      The level of DNA-DNA relatedness between strain UDC329(T) and S. fodinae JC15(T)
      was, however, only 27.4%. On the basis of phenotypic, genotypic and DNA-DNA
      relatedness data, strain UDC329(T) represents a novel species in the genus
      Shewanella, for which the name Shewanella dokdonensis sp. nov. is proposed. The
      type strain is UDC329(T) (=KCTC 22898(T)=DSM 23626(T)).

PMID- 21890723
TI  - Planktotalea frisia gen. nov., sp. nov., isolated from the southern North Sea.
AB  - A heterotrophic, aerobic bacterium, designated strain SH6-1(T), was obtained from
      a seawater sample collected from the open North Sea during a phytoplankton bloom.
      Strain SH6-1(T) was isolated from a 10(-6) dilution culture, which indicated a
      high abundance of this organism in the environmental sample. 16S rRNA gene
      sequence comparison revealed that strain SH6-1(T) belonged to the marine
      Roseobacter clade (order Rhodobacterales) within the class Alphaproteobacteria.
      Pelagicola litoralis CL-ES2(T) was the closest phylogenetic neighbour (96.4% 16S
      rRNA gene sequence similarity). Cells of strain SH6-1(T) were small or elongated
      irregular rods. Optimal growth occurred between 20 and 25  degrees C and between
      pH 7.5 and 9.0 with peptone and yeast extract. On marine agar, the isolate formed
      non-pigmented, small, circular, convex colonies. For growth, cells required
      sodium ions and the vitamins pantothenic acid and nicotinic acid amide. The DNA
      G+C content was 53.8 mol%. The fatty acids (>1%) were C(10:0) 3-OH, C(16:0),
      C(12:1), C(12:1) 3-OH, C(18:0), C(18:1)omega7c, C(18:2) and 11-methyl
      C(18:1)omega7c. The polar lipid pattern indicated the presence of
      phosphatidylcholine, phosphatidylglycerol, an unidentified aminolipid and one
      unidentified phospholipid. The major respiratory lipoquinone was ubiquinone Q-10.
      Strain SH6-1(T) contained the genes pufLM, which code for the bacterial
      photosynthesis reaction centre; however, no bacteriochlorophyll a could be
      detected. Physiological, genotypic and phenotypic differences from P. litoralis
      support the description of a novel genus and species, for which we suggest the
      name Planktotalea frisia gen. nov., sp. nov; the type strain of the type species
      is SH6-1(T) (=DSM 23709(T)=LMG 25294(T)).

PMID- 21890725
TI  - Nocardiopsis coralliicola sp. nov., isolated from the gorgonian coral, Menella
      praelonga.
AB  - An actinobacterial strain, SCSIO 10427(T), was isolated from a gorgonian coral
      sample collected from Weizhou Island, Guangxi province, China, and its taxonomic
      position was investigated using a polyphasic approach. The organism was found to
      have a range of chemical and morphological properties consistent with its
      classification in the genus Nocardiopsis. Phylogenetic analysis indicated that
      16S rRNA gene sequence similarity between strain SCSIO 10427(T) and type strains
      of other recognized members of the genus Nocardiopsis was lower than 98.4%.
      Furthermore, phenotypic characteristics revealed that the strain differed from
      the currently recognized species of the genus Nocardiopsis. Therefore, strain
      SCSIO 10427(T) represents a novel species of the genus Nocardiopsis, for which
      the name Nocardiopsis coralliicola sp. nov. is proposed. The type strain is SCSIO
      10427(T) (=CCTCC AA 2011010(T)=DSM 45611(T)).

PMID- 21890726
TI  - Mucilaginibacter soli sp. nov., isolated from Arctic tundra soil.
AB  - A novel pale-pink-coloured strain, designated R9-65(T), was isolated from a
      tundra soil near Ny-Alesund, Svalbard Archipelago, Norway (78 degrees  N). The
      cells were facultatively anaerobic, Gram-staining-negative, non-motile and rod
      shaped. Growth occurred at 4-32  degrees C (optimum, 25-28  degrees C), at pH 5.0
      9.0 (optimum, pH 6.0-7.0) and with 0-1.0% (w/v) NaCl (optimum, no NaCl).
      Flexirubin-type pigments were absent. Phylogenetic analysis based on 16S rRNA
      gene sequences indicated that strain R9-65(T) belonged to the genus
      Mucilaginibacter in the family Sphingobacteriaceae. The 16S rRNA gene sequence
      similarity between strain R9-65(T) and type strains of related species ranged
      from 93.4 to 96.6%. Strain R9-65(T) contained summed feature 3 (C(16:1)omega7c
      and/or C(16:1)omega6c, 34.3%) and iso-C(15:0) (20.3%) as major cellular fatty
      acids, MK-7 as the major respiratory quinone, and phosphatidylethanolamine as the
      main polar lipid. The DNA G+C content of strain R9-65(T) was 47.2 mol%. On the
      basis of phylogenetic, physiological and chemotaxonomic data, strain R9-65(T) is
      considered to represent a novel species of the genus Mucilaginibacter, for which
      the name Mucilaginibacter soli sp. nov. is proposed. The type strain is R9-65(T)
      (=CCTCC AB 2010331(T)=NRRL B-59458(T)).

PMID- 21890727
TI  - Lysobacter arseniciresistens sp. nov., an arsenite-resistant bacterium isolated
      from iron-mined soil.
AB  - A Gram-negative, aerobic, motile, rod-shaped, arsenite [As(III)]-resistant
      bacterium, designated strain ZS79(T), was isolated from subsurface soil of an
      iron mine in China. Phylogenetic analyses based on 16S rRNA gene sequences
      revealed that strain ZS79(T) clustered closely with strains of five Lysobacter
      species, with 96.9, 96.1, 96.0, 95.8 and 95.3% sequence similarities to
      Lysobacter concretionis Ko07(T), L. daejeonensis GH1-9(T), L. defluvii IMMIB APB
      9(T), L. spongiicola KMM 329(T) and L. ruishenii CTN-1(T), respectively. The
      major cellular fatty acids were iso-C(15:0) (28.6%), iso-C(17:1)omega9c (19.9%),
      iso-C(16:0) (13.6%), iso-C(11:0) (12.6%) and iso-C(11:0) 3-OH (12.4%). The
      genomic DNA G+C content was 70.7 mol% and the major respiratory quinone was Q-8.
      The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine,
      phosphatidylglycerol and an unknown phospholipid. On the basis of morphological
      and physiological/biochemical characteristics, phylogenetic position and
      chemotaxonomic data, this strain is considered to represent a novel species of
      the genus Lysobacter, for which the name Lysobacter arseniciresistens sp. nov. is
      proposed; the type strain is ZS79(T) (=CGMCC 1.10752(T)=KCTC 23365(T)).

PMID- 21890728
TI  - Hydrotalea sandarakina sp. nov., isolated from a hot spring runoff, and emended
      descriptions of the genus Hydrotalea and the species Hydrotalea flava.
AB  - Two bacterial isolates, designated AF-51(T) and AF-50, with an optimum growth
      temperature of about 45  degrees C and an optimum pH for growth between 6.0 and
      6.5, were recovered from a hot spring in the Furnas, Area da Fonte 1825, on the
      Island of Sao Miguel in the Azores. Based on 16S rRNA gene sequence analysis,
      these strains were related most closely to the type strain of Hydrotalea flava at
      a pairwise similarity of 95.7%. The two strains were orange-pigmented and formed
      non-motile, rod-shaped cells that stained Gram-negative and were aerobic and
      oxidase- and catalase-positive. The major fatty acids were iso-C(15:0), iso
      C(17:0) 3-OH and iso-C(16:0). The major respiratory quinone was menaquinone 7.
      Based on phylogenetic, physiological and biochemical characteristics, these
      strains from the Azores are considered to represent a single novel species of the
      genus Hydrotalea, for which the name Hydrotalea sandarakina sp. nov. is proposed.
      The type strain is AF-51(T) (=DSM 23241(T)=LMG 25526(T)). We provide emended
      descriptions of the genus Hydrotalea and of H. flava to reflect new results
      obtained in this study.

PMID- 21890729
TI  - Albidovulum xiamenense sp. nov., a moderately thermophilic bacterium from a
      terrestrial hot spring.
AB  - An aerobic, motile, moderately thermophilic, rod-shaped bacterium, strain YBY
      7(T), was isolated from a terrestrial hot spring of a garden exhibition located
      in Xiamen City, Fujian Province, People's Republic of China. Cells of strain YBY
      7(T) were Gram-negative, irregular rods, 2-6 um long and 0.4-0.6 um wide, with
      polar flagella, and the organism formed beige colonies. The temperature and pH
      ranges for growth of strain YBY-7(T) were 28-65  degrees C (optimum 50-58 
      degrees C) and pH 6.5-9.5 (optimum pH 7.5-8.5). Growth occurred in the presence
      of 5.5% NaCl (optimum 3.0%). Phylogenetic analysis based on the 16S rRNA gene
      sequence revealed that Albidovulum inexpectatum FRR-10(T) was its closest
      neighbour (95.9% similarity). Ubiquinone (Q-10) was the sole respiratory quinone
      and the DNA G+C content of strain YBY-7(T) was 70.6 mol%. The predominant polar
      lipids were phosphatidylcholine, phosphatidylglycerol and
      phosphatidylethanolamine. The major fatty acids were C(18:1)omega7c (29.3%),
      C(19:0) cyclo omega8c (25.6%), C(18:0) (23.6%) and C(16:0) (9.6%). Based on its
      physiological characteristics and our phylogenetic analysis, we propose that
      strain YBY-7(T) represents a novel species of the genus Albidovulum, for which
      the name Albidovulum xiamenense sp. nov. is proposed, with the type strain YBY
      7(T) (=MCCC 1A06317(T) =CGMCC 1.10789(T) =LMG 26247(T)).

PMID- 21890730
TI  - Methanobacterium lacus sp. nov., isolated from the profundal sediment of a
      freshwater meromictic lake.
AB  - An autotrophic, hydrogenotrophic methanogen, designated strain 17A1(T), was
      isolated from the profundal sediment of the meromictic Lake Pavin, France. The
      cells of the novel strain, which were non-motile, Gram-staining-negative rods
      that measured 2-15 um in length and 0.2-0.4 um in width, grew as filaments.
      Strain 17A1(T) grew in a mineral medium and its growth was stimulated by the
      addition of yeast extract, vitamins, acetate or rumen fluid. Penicillin,
      vancomycin and kanamycin reduced growth but did not completely inhibit it. Growth
      occurred at 14-41  degrees C (optimum 30  degrees C), at pH 5.0-8.5 (optimum pH
      6.5) and with 0-0.4 M NaCl (optimum 0.1 M). The novel strain utilized H(2)/CO(2)
      and methanol/H(2) as substrates but not formate, acetate, methylamine/H(2),
      isobutanol or 2-propanol. Its genomic DNA G+C content was 37.0 mol%. In
      phylogenetic analyses based on 16S rRNA gene sequences, strain 17A1(T) appeared
      to be a member of the genus Methanobacterium, with Methanobacterium beijingense 8
      2(T) (96.3% sequence similarity) identified as the most closely related
      established species. Based on phenotypic and phylogenetic data, strain 17A1(T)
      represents a novel species of methanogen within the genus Methanobacterium, for
      which the name Methanobacterium lacus sp. nov. is proposed. The type strain is
      17A1(T) (=DSM 24406(T)=JCM 17760(T)).

PMID- 21890731
TI  - Methylophaga lonarensis sp. nov., a moderately haloalkaliphilic methylotroph
      isolated from the soda lake sediments of a meteorite impact crater.
AB  - A moderately haloalkaliphilic methylotrophic bacterium possessing the ribulose
      monophosphate pathway for carbon assimilation, designated MPL(T), was isolated
      from Lonar Lake sediment microcosms that were oxidizing methane for two weeks.
      The isolate utilized methanol and was an aerobic, Gram-negative, asporogenous,
      motile, short rod that multiplied by binary fission. The isolate required
      NaHCO(3) or NaCl for growth and, although not auxotrophic for vitamin B(12), had
      enhanced growth with vitamin B(12). Optimal growth occurred with 0.5-2% (w/v)
      NaCl, at 28-30  degrees C and at pH 9.0-10.0. The cellular fatty acid profile
      consisted primarily of straight-chain saturated C(16:0) and unsaturated
      C(16:1)omega7c and C(18:1)omega7c. The major ubiquinone was Q-8. The dominant
      phospholipids were phosphatidylethanolamine, phosphatidylglycerol and
      diphosphatidylglycerol. Cells accumulated ectoine as the main compatible solute.
      The DNA G+C content was 50.0 mol%. The isolate exhibited 94.0-95.4% 16S rRNA gene
      sequence similarity with the type strains of methylotrophs belonging to the genus
      Methylophaga and 31% DNA-DNA relatedness with the reference strain, Methylophaga
      alcalica VKM B-2251(T). It is proposed that strain MPL(T) represents a novel
      species, Methylophaga lonarensis sp. nov. (type strain MPL(T)=VKM B-2684(T)=MCC
      1002(T)).

PMID- 21890732
TI  - Nonomuraea soli sp. nov., an actinomycete isolated from soil.
AB  - A straight-chain, spore-forming actinobacterium, strain YIM 120770(T), was
      isolated from soil. Phylogenetic analysis on the basis of 16S rRNA gene sequence
      comparisons revealed that the isolate represents a distinct cluster within the
      clade comprising the genus Nonomuraea and is related most closely to Nonomuraea
      rhizophila YIM 67092(T) (96.5% similarity). Cells of strain YIM 120770(T) grew in
      the presence of 0-3% (w/v) NaCl, at 15-37  degrees C and at pH 7.0-8.0. The
      diagnostic amino acid was meso-diaminopimelic acid, cell hydrolysates contained
      madurose, glucose, mannose, ribose and galactose, the predominant cellular fatty
      acids were 10-methyl C(17:0) and iso-C(16:0), and the DNA G+C content was 66.4
      mol%, data consistent with affiliation of strain YIM 120770(T) to the genus
      Nonomuraea. Strain YIM 120770(T) shared low levels of 16S rRNA gene sequence
      similarity (<97%) with the type strains of recognized species of the genus
      Nonomuraea and could be differentiated from its closest phylogenetic relative
      based on phenotypic characteristics. These results suggested that strain YIM
      120770(T) represents a novel species of the genus Nonomuraea, for which the name
      Nonomuraea soli sp. nov. is proposed. The type strain is YIM 120770(T) (=DSM
      45533(T)=JCM 17347(T)).

PMID- 21890734
TI  - Role of residue 87 in the activity and regioselectivity of clozapine metabolism
      by drug-metabolizing CYP102A1 M11H: application for structural characterization
      of clozapine GSH conjugates.
AB  - In the present study, a site-saturation mutagenesis library of drug-metabolizing
      CYP102A1 M11H with all 20 amino acids at position 87 was applied as a biocatalyst
      for the production of stable and reactive metabolites of clozapine. Clozapine is
      an atypical antipsychotic drug in which formation of reactive metabolites is
      considered to be responsible for several adverse drug reactions. Reactive
      intermediates of clozapine can be inactivated by GSH to multiple GSH conjugates
      by nonenzymatic and glutathione transferase (GST)-mediated conjugation reactions.
      The structures of several GST-dependent metabolites have not yet been elucidated
      unequivocally. The present study shows that the nature of the amino acid at
      position 87 of CYP102A1 M11H strongly determines the activity and
      regioselectivity of clozapine metabolism. Some mutants showed preference for N
      demethylation and N-oxidation, whereas others showed high selectivity for
      bioactivation to reactive intermediates. The mutant containing Phe87 showed high
      activity and high selectivity for the bioactivation pathway and was used for the
      large-scale production of GST-dependent GSH conjugates by incubation in the
      presence of recombinant human GST P1-1. Five human-relevant GSH adducts were
      produced at high levels, enabling structural characterization by (1)H NMR. This
      work shows that drug-metabolizing CYP102A1 mutants, in combination with GSTs, are
      very useful tools for the generation of GSH conjugates of reactive metabolites of
      drugs to enable their isolation and structural elucidation.

PMID- 21890733
TI  - Proposal to reclassify Brenneria quercina (Hildebrand and Schroth 1967) Hauben et
      al. 1999 into a new genus, Lonsdalea gen. nov., as Lonsdalea quercina comb. nov.,
      descriptions of Lonsdalea quercina subsp. quercina comb. nov., Lonsdalea quercina
      subsp. iberica subsp. nov. and Lonsdalea quercina subsp. britannica subsp. nov.,
      emendation of the description of the genus Brenneria, reclassification of Dickeya
      dieffenbachiae as Dickeya dadantii subsp. dieffenbachiae comb. nov., and
      emendation of the description of Dickeya dadantii.
AB  - Bacterial isolates from oak trees in Spain and Britain, showing symptoms of bark
      canker and Acute Oak Decline (AOD), respectively, were examined by a polyphasic
      approach. Both 16S rRNA gene sequencing and multilocus sequence analysis (MLSA),
      based on partial sequences of gyrB, rpoB, infB and atpD genes, revealed that the
      isolates were separated into two genetic groups according to their origin. Their
      closest phylogenetic relative was Brenneria quercina, the causal agent of drippy
      nut disease of oak, which clustered distant to the other species of the genus
      Brenneria. MLSA data for species of the genera Brenneria, Pectobacterium,
      Dickeya, Erwinia, Pantoea and Samsonia confirmed the polyphyletic nature of the
      genus Brenneria and indicated synonymy of Dickeya dadantii and Dickeya
      dieffenbachiae. DNA-DNA hybridization experiments confirmed this synonymy and
      also revealed DNA-DNA relatedness values of 58-73% between the new oak isolates
      and B. quercina. Phenotypic and/or chemotaxonomic methods allowed B. quercina and
      the two genetic groups of new oak isolates to be discriminated from other
      recognized species of the genus Brenneria and from members of the closely related
      genera Dickeya, Pectobacterium and Samsonia. Based on the data obtained, the
      following taxonomic proposals are made: (1) reclassification of B. quercina as
      the type species of a novel genus, Lonsdalea gen. nov., as Lonsdalea quercina
      comb. nov. (type strain LMG 2724(T)=ATCC 29281(T)=CCUG 48867(T)=CFBP 3617(T)=CIP
      105201(T)=DSM 4561(T)=ICMP 1845(T)), (2) classification of the oak isolates as
      Lonsdalea quercina subsp. iberica subsp. nov. (type strain LMG26264(T)=NCPPB
      4490(T)) and Lonsdalea quercina subsp. britannica subsp. nov. (type strain LMG
      26267(T)=NCPPB 4481(T)) and leading to the automatic creation of Lonsdalea
      quercina subsp. quercina subsp. nov. (type strain LMG 2724(T)=ATCC 29281(T)), (3)
      emendation of the description of the genus Brenneria, and (4) reclassification of
      Dickeya dieffenbachiae as Dickeya dadantii subsp. dieffenbachiae comb. nov. (type
      strain LMG 25992(T)=CFBP 2051(T)), with the automatic creation of Dickeya
      dadantii subsp. dadantii subsp. nov. (type strain LMG 25991(T)=CFBP 1269(T)).

PMID- 21890735
TI  - Proluciferin acetals as bioluminogenic substrates for cytochrome P450 activity
      and probes for CYP3A inhibition.
AB  - Cytochrome P450 (P450) assays use probe substrates to interrogate the influence
      of new chemical entities toward P450 enzymes. We report the synthesis and study
      of a family of bioluminogenic luciferin acetal substrates that are oxidized by
      P450 enzymes to form luciferase substrates. The luciferin acetals were screened
      against a panel of purified P450 enzymes. In particular, one proluciferin acetal
      has demonstrated sensitive and selective CYP3A4-catalyzed oxidation to a
      luciferin ester-K(m) and k(cat) are 2.88 MUM and 5.87 pmol metabolite . min(-1) .
      pmol enzyme(-1), respectively. The proluciferin acetal was used as a probe
      substrate to measure IC(50) values of known inhibitors against recombinant CYP3A4
      or human liver microsomes. IC(50) values for the known inhibitors correlate
      strongly with IC(50) values calculated from the traditional high-performance
      liquid chromatography-based probe substrate testosterone. Luciferin acetals are
      rapidly oxidized to unstable hemi-orthoesters by CYP3A resulting in luciferin
      esters and, therefore, are conducive to simple rapid CYP3A bioluminescent assays.

PMID- 21890736
TI  - Aryl hydrocarbon receptor-mediated induction of Stearoyl-CoA desaturase 1 alters
      hepatic fatty acid composition in TCDD-elicited steatosis.
AB  - 2,3,7,8-tetrachlorodibenzo-rho-dioxin (TCDD) induces hepatic dyslipidemia
      mediated by the aryl hydrocarbon receptor (AhR). Stearoyl-CoA desaturase 1 (Scd1)
      performs the rate-limiting step in monounsaturated fatty acid (MUFA) synthesis,
      desaturating 16:0 and 18:0 into 16:1n7 and 18:1n9, respectively. To further
      examine the role of Scd1 in TCDD-induced hepatotoxicity, comparative studies were
      performed in Scd1(+/+) and Scd1(-/-) mice treated with 30 MUg/kg TCDD. TCDD
      induced Scd1 activity, protein, and messenger RNA (mRNA) levels approximately
      twofold. In Scd1(+/+) mice, hepatic effects were marked by increased
      vacuolization and inflammation and a 3.5-fold increase in serum alanine
      aminotransferase (ALT) levels. Hepatic triglycerides (TRGs) were induced 3.9-fold
      and lipid profiling by gas chromatography-mass spectroscopy measured a 1.9-fold
      increase in fatty acid (FA) levels, consistent with the induction of lipid
      transport genes. Induction of Scd1 altered FA composition by decreasing saturated
      fatty acid (SFA) molar ratios 8% and increasing MUFA molar ratios 9%.
      Furthermore, ChIP-chip analysis revealed AhR enrichment (up to 5.7-fold), and
      computational analysis identified 16 putative functional dioxin response elements
      (DREs) within Scd1 genomic loci. Band shift assays confirmed AhR binding with
      select DREs. In Scd1(-/-) mice, TCDD induced minimal hepatic vacuolization and
      inflammation, while serum ALT levels remained unchanged. Although Scd1 deficiency
      attenuated TCDD-induced TRG accumulation, overall FA levels remained unchanged
      compared with Scd1(+/+) mice. In Scd1(-/-) mice, TCDD induced SFA ratios 8%,
      reduced MUFA ratios 13%, and induced polyunsaturated fatty acid ratios 5%
      relative to treated Scd1(+/+) mice. Collectively, these results suggest that AhR
      regulation of Scd1 not only alters lipid composition but also contributes to the
      hepatotoxicity of TCDD.

PMID- 21890737
TI  - Cardiomyopathy is associated with ribosomal protein gene haplo-insufficiency in
      Drosophila melanogaster.
AB  - The Minute syndrome in Drosophila melanogaster is characterized by delayed
      development, poor fertility, and short slender bristles. Many Minute loci
      correspond to disruptions of genes for cytoplasmic ribosomal proteins, and
      therefore the phenotype has been attributed to alterations in translational
      processes. Although protein translation is crucial for all cells in an organism,
      it is unclear why Minute mutations cause effects in specific tissues. To
      determine whether the heart is sensitive to haplo-insufficiency of genes encoding
      ribosomal proteins, we measured heart function of Minute mutants using optical
      coherence tomography. We found that cardiomyopathy is associated with the Minute
      syndrome caused by haplo-insufficiency of genes encoding cytoplasmic ribosomal
      proteins. While mutations of genes encoding non-Minute cytoplasmic ribosomal
      proteins are homozygous lethal, heterozygous deficiencies spanning these non
      Minute genes did not cause a change in cardiac function. Deficiencies of genes
      for non-Minute mitochondrial ribosomal proteins also did not show abnormal
      cardiac function, with the exception of a heterozygous disruption of mRpS33. We
      demonstrate that cardiomyopathy is a common trait of the Minute syndrome caused
      by haplo-insufficiency of genes encoding cytoplasmic ribosomal proteins. In
      contrast, most cases of heterozygous deficiencies of genes encoding non-Minute
      ribosomal proteins have normal heart function in adult Drosophila.

PMID- 21890739
TI  - Disentangling prenatal and postnatal maternal genetic effects reveals persistent
      prenatal effects on offspring growth in mice.
AB  - Mothers are often the most important determinant of traits expressed by their
      offspring. These "maternal effects" (MEs) are especially crucial in early
      development, but can also persist into adulthood. They have been shown to play a
      role in a diversity of evolutionary and ecological processes, especially when
      genetically based. Although the importance of MEs is becoming widely appreciated,
      we know little about their underlying genetic basis. We address the dearth of
      genetic data by providing a simple approach, using combined genotype information
      from parents and offspring, to identify "maternal genetic effects" (MGEs)
      contributing to natural variation in complex traits. Combined with experimental
      cross-fostering, our approach also allows for the separation of pre- and
      postnatal MGEs, providing rare insights into prenatal effects. Applying this
      approach to an experimental mouse population, we identified 13 ME loci affecting
      body weight, most of which (12/13) exhibited prenatal effects, and nearly half
      (6/13) exhibiting postnatal effects. MGEs contributed more to variation in body
      weight than the direct effects of the offsprings' own genotypes until mice
      reached adulthood, but continued to represent a major component of variation
      through adulthood. Prenatal effects always contributed more variation than
      postnatal effects, especially for those effects that persisted into adulthood.
      These results suggest that MGEs may be an important component of genetic
      architecture that is generally overlooked in studies focused on direct mapping
      from genotype to phenotype. Our approach can be used in both experimental and
      natural populations, providing a widely practicable means of expanding our
      understanding of MGEs.

PMID- 21890740
TI  - Role of testis-specific gene expression in sex-chromosome evolution of Anopheles
      gambiae.
AB  - Gene expression in Anopheles gambiae shows a deficiency of testis-expressed genes
      on the X chromosome associated with an excessive movement of retrogene
      duplication. We suggest that the degeneration of sex chromosomes in this
      monandrous species is likely the result of pressures from X inactivation, dosage
      compensation, and sexual antagonism.

PMID- 21890738
TI  - MicroRNA sequence variation potentially contributes to within-species functional
      divergence in the nematode Caenorhabditis briggsae.
AB  - Mounting evidence points to differences in gene regulation as a major source of
      phenotypic variation. MicroRNA-mediated post-transcriptional regulation has
      emerged recently as a key factor controlling gene activity during development.
      MicroRNA genes are abundant in genomes, acting as managers of gene expression by
      directing translational repression. Thus, understanding the role of microRNA
      sequence variation within populations is essential for fully dissecting the
      origin and maintenance of phenotypic diversity in nature. In this study, we
      investigate allelic variation at microRNA loci in the nematode Caenorhabditis
      briggsae, a close relative of C. elegans. Phylogeographic structure in C.
      briggsae partitions most strains from around the globe into a "temperate" or a
      "tropical" clade, with a few strains having divergent, geographically restricted
      genotypes. Remarkably, strains that follow this latitudinal dichotomy also differ
      in temperature-associated fitness. With this phylogeographic pattern in mind, we
      examined polymorphisms in 18 miRNAs in a global sample of C. briggsae isolates
      and tested whether newly isolated strains conform to this phylogeography.
      Surprisingly, nucleotide diversity is relatively high in this class of gene that
      generally experiences strong purifying selection. In particular, we find that
      miRNAs in C. briggsae are substantially more polymorphic than in Arabidopsis
      thaliana, despite similar background levels of neutral site diversity between the
      two species. We find that some mutations suggest functional divergence on the
      basis of requirements for target site recognition and computational prediction of
      the effects of the polymorphisms on RNA folding. These findings demonstrate the
      potential for miRNA polymorphisms to contribute to phenotypic variation within a
      species. Sequences were deposited in GenBank under accession nos. JN251323
      JN251744.

PMID- 21890741
TI  - Rapid GAL gene switch of Saccharomyces cerevisiae depends on nuclear Gal3, not
      nucleocytoplasmic trafficking of Gal3 and Gal80.
AB  - The yeast transcriptional activator Gal4 localizes to UAS(GAL) sites even in the
      absence of galactose but cannot activate transcription due to an association with
      the Gal80 protein. By 4 min after galactose addition, Gal4-activated gene
      transcription ensues. It is well established that this rapid induction arises
      through a galactose-triggered association between the Gal80 and Gal3 proteins
      that decreases the association of Gal80 and Gal4. How this happens
      mechanistically remains unclear. Strikingly different hypotheses prevail
      concerning the possible roles of nucleocytoplasmic distribution and trafficking
      of Gal3 and Gal80 and where in the cell the initial Gal3-Gal80 association
      occurs. Here we tested two conflicting hypotheses by evaluating the subcellular
      distribution and dynamics of Gal3 and Gal80 with reference to induction kinetics.
      We determined that the rates of nucleocytoplasmic trafficking for both Gal80 and
      Gal3 are slow relative to the rate of induction. We find that depletion of the
      nuclear pool of Gal3 slows the induction kinetics. Thus, nuclear Gal3 is critical
      for rapid induction. Fluorescence-recovery-after-photobleaching experiments
      provided data suggesting that the Gal80-Gal4 complex exhibits kinetic stability
      in the absence of galactose. Finally, we detect Gal3 at the UAS(GAL) only if
      Gal80 is covalently linked to the DNA-binding domain. Taken altogether, these new
      findings lead us to propose that a transient interaction of Gal3 with Gal4
      associated Gal80 could explain the rapid response of this system. This notion
      could also explain earlier observations.

PMID- 21890742
TI  - Epigenetic QTL mapping in Brassica napus.
AB  - There is increasing evidence that epigenetic marks such as DNA methylation
      contribute to phenotypic variation by regulating gene transcription,
      developmental plasticity, and interactions with the environment. However,
      relatively little is known about the relationship between the stability and
      distribution of DNA methylation within chromosomes and the ability to detect
      trait loci. Plant genomes have a distinct range of target sites and more
      extensive DNA methylation than animals. We analyzed the stability and
      distribution of epialleles within the complex genome of the oilseed crop plant
      Brassica napus. For methylation sensitive AFLP (MSAP) and retrotransposon (RT)
      epimarkers, we found a high degree of stability, with 90% of mapped markers
      retaining their allelic pattern in contrasting environments and developmental
      stages. Moreover, for two distinct parental lines 97% of epialleles were
      transmitted through five meioses and segregated in a mapping population. For the
      first time we have established the genetic position for 17 of the 19 centromeres
      within this amphidiploid species. Epiloci and genetic loci were distributed
      within distinct clusters, indicating differential detection of recombination
      events. This enabled us to identify additional significant QTL associated with
      seven important agronomic traits in the centromeric regions of five linkage
      groups.

PMID- 21890744
TI  - Fitness landscapes: an alternative theory for the dominance of mutation.
AB  - Deleterious mutations tend to be recessive. Several theories, notably those of
      Fisher (based on selection) and Wright (based on metabolism), have been put
      forward to explain this pattern. Despite a long-lasting debate, the matter
      remains unresolved. This debate has focused on the average dominance of
      mutations. However, we also know very little about the distribution of dominance
      coefficients among mutations, and about its variation across environments. In
      this article we present a new approach to predicting this distribution. Our
      approach is based on a phenotypic fitness landscape model. First, we show that
      under a very broad range of conditions (and environments), the average dominance
      of mutation of small effects should be approximately one-quarter as long as
      adaptation of organisms to their environment can be well described by stabilizing
      selection on an arbitrary set of phenotypic traits. Second, the theory allows
      predicting the whole distribution of dominance coefficients among mutants.
      Because it provides quantitative rather than qualitative predictions, this theory
      can be directly compared to data. We found that its prediction on mean dominance
      (average dominance close to 0.25) agreed well with the data, based on a meta
      analysis of dominance data for mildly deleterious mutations. However, a simple
      landscape model does not account for the dominance of mutations of large effects
      and we provide possible extension of the theory for this class of mutations.
      Because dominance is a central parameter for evolutionary theory, and because
      these predictions are quantitative, they set the stage for a wide range of
      applications and further empirical tests.

PMID- 21890743
TI  - Pervasive recombination and sympatric genome diversification driven by frequency
      dependent selection in Borrelia burgdorferi, the Lyme disease bacterium.
AB  - How genomic diversity within bacterial populations originates and is maintained
      in the presence of frequent recombination is a central problem in understanding
      bacterial evolution. Natural populations of Borrelia burgdorferi, the bacterial
      agent of Lyme disease, consist of diverse genomic groups co-infecting single
      individual vertebrate hosts and tick vectors. To understand mechanisms of
      sympatric genome differentiation in B. burgdorferi, we sequenced and compared 23
      genomes representing major genomic groups in North America and Europe. Linkage
      analysis of >13,500 single-nucleotide polymorphisms revealed pervasive horizontal
      DNA exchanges. Although three times more frequent than point mutation,
      recombination is localized and weakly affects genome-wide linkage disequilibrium.
      We show by computer simulations that, while enhancing population fitness,
      recombination constrains neutral and adaptive divergence among sympatric genomes
      through periodic selective sweeps. In contrast, simulations of frequency
      dependent selection with recombination produced the observed pattern of a large
      number of sympatric genomic groups associated with major sequence variations at
      the selected locus. We conclude that negative frequency-dependent selection
      targeting a small number of surface-antigen loci (ospC in particular)
      sufficiently explains the maintenance of sympatric genome diversity in B.
      burgdorferi without adaptive divergence. We suggest that pervasive recombination
      makes it less likely for local B. burgdorferi genomic groups to achieve host
      specialization. B. burgdorferi genomic groups in the northeastern United States
      are thus best viewed as constituting a single bacterial species, whose generalist
      nature is a key to its rapid spread and human virulence.

PMID- 21890745
TI  - Perceptual measurement in schizophrenia: promising electrophysiology and
      neuroimaging paradigms from CNTRICS.
AB  - The sixth meeting of the Cognitive Neuroscience Treatment Research to Improve
      Cognition in Schizophrenia (CNTRICS) focused on selecting promising imaging
      paradigms for each of the cognitive constructs selected in the first CNTRICS
      meeting. In the domain of perception, the 2 constructs of interest were "gain
      control" and "visual integration." CNTRICS received 6 task nominations for
      imaging paradigms for gain control and 3 task nominations for integration. The
      breakout group for perception evaluated the degree to which each of these tasks
      met prespecified criteria. For gain control, the breakout group believed that one
      task (mismatch negativity) was already mature and was being incorporated into
      multisite clinical trials. The breakout group recommended that 1 visual task
      (steady-state visual evoked potentials to magnocellular- vs parvocellular-biased
      stimuli) and 2 auditory measures (an event-related potential (ERP) measure of
      corollary discharge and a functional magnetic resonance imaging (fMRI) version of
      prepulse inhibition of startle) be adapted for use in clinical trials in
      schizophrenia research. For visual integration, the breakout group recommended
      that fMRI and ERP versions of a contour integration test and an fMRI version of a
      coherent motion test be adapted for use in clinical trials. This manuscript
      describes the ways in which each of these tasks met the criteria used in the
      breakout group to evaluate and recommend tasks for further development.

PMID- 21890746
TI  - Effects of ERCC2 Lys751Gln (A35931C) and CCND1 (G870A) polymorphism on outcome of
      advanced-stage squamous cell carcinoma of the head and neck are treatment
      dependent.
AB  - BACKGROUND: Germline variation in DNA damage response may explain variable
      treatment outcomes in squamous cell carcinoma of the head and neck (SCCHN). By
      grouping patients according to stage and radiation treatment, we compared SCCHN
      survival with regard to ERCC2 A35931C (Lys751Gln, rs13181) and CCND1 G870A
      (Pro241Pro, rs9344) genotypes. METHODS: In a hospital-based SCCHN case series
      (all white, 24.7% female, mean age 58.4 years), this treatment-outcome cohort
      study genotyped 275 stage III-IV cases that were initially treated with radiation
      (with or without chemotherapy) and 80 stage III-IV and 130 stage I-II cases that
      were initially treated without radiation or chemotherapy and used Kaplan-Meier
      and Cox regression analyses to compare genotype groups on the basis of overall,
      disease-specific, progression-free, and recurrence-free survival rates. RESULTS:
      ERCC2 35931 AA predicted worse survival in stage III-IV cases treated with
      radiation [multiply-adjusted HR = 1.66, 95% confidence interval (CI), 1.15-2.40;
      HR over the first 3 follow-up years = 1.92; 95% CI, 1.28-2.88] and better
      survival in stage III-IV cases not treated with radiation (HR = 0.26; 95% CI,
      0.11-0.62). Although not associated with survival in stage III-IV cancers treated
      with radiation (HR = 1.00; 95% CI, 0.67-1.51), CCND1-870 GG predicted better
      survival in stage III-IV cancers not treated with radiation (HR = 0.14; 95% CI,
      0.04-0.50). Survival in stage I-II did not depend on ERCC2 A35931C or CCND1 G870A
      genotype. CONCLUSIONS: Although promoting tumor progression in untreated
      patients, germline differences in DNA-repair or cell-cycle control may improve
      treatment outcome in patients treated with DNA-damaging agents. IMPACT: ERCC2
      A35931C may help distinguish advanced stage SCCHN with better outcomes from
      radiation treatment.

PMID- 21890747
TI  - 3,5-bis(2,4-difluorobenzylidene)-4-piperidone, a novel compound that affects
      pancreatic cancer growth and angiogenesis.
AB  - Dysregulated Notch signaling plays an important role in the progression of
      cancer. Notch signaling affects tumor growth and angiogenesis through the actions
      of its ligand Jagged-1. In this study, we developed a novel compound 3,5-bis(2,4
      difluorobenzylidene)-4-piperidone (DiFiD) and determined that it inhibits cancer
      cell growth and its effects on Notch signaling. Intraperitoneal administration of
      DiFiD significantly suppressed growth of pancreatic cancer tumor xenografts.
      There was a reduction in CD31-positive blood vessels, suggesting that there was
      an effect on angiogenesis. In vitro, DiFiD inhibited the proliferation of various
      human and mouse pancreatic cancer cells while increasing activated caspase-3.
      Cell-cycle analyses showed that DiFiD induced G(2)-M arrest and decreased the
      expression of cell-cycle-related proteins cyclin A1 and D1 while upregulating
      cyclin-dependent kinase inhibitor p21WAF1. We next determined the mechanism of
      action. DiFiD reduced Notch-1 activation, resulting in reduced expression of its
      downstream target protein Hes-1. We further determined that the reduced Notch-1
      activation was due to reduction in the ligand Jagged-1 and two critical
      components of the gamma-secretase enzyme complex presenilin-1 and nicastrin.
      Ectopic expression of the Notch intracellular domain rescued the cells from DiFiD
      mediated growth suppression. DiFiD-treated tumor xenografts also showed reduced
      levels of Jagged-1 and the gamma-secretase complex proteins presenilin-1 and
      nicastrin. Taken together, these data suggest that DiFiD is a novel potent
      therapeutic agent that can target different aspects of the Notch signaling
      pathway to inhibit both tumor growth and angiogenesis.

PMID- 21890748
TI  - Subunit stabilization and polyethylene glycolation of cocaine esterase improves
      in vivo residence time.
AB  - No small-molecule therapeutic is available to treat cocaine addiction, but enzyme
      based therapy to accelerate cocaine hydrolysis in serum has gained momentum.
      Bacterial cocaine esterase (CocE) is the fastest known native enzyme that
      hydrolyzes cocaine. However, its lability at 37 degrees C has limited its
      therapeutic potential. Cross-linking subunits through disulfide bridging is
      commonly used to stabilize multimeric enzymes. Herein we use structural methods
      to guide the introduction of two cysteine residues within dimer interface of CocE
      to facilitate intermolecular disulfide bond formation. The disulfide-crosslinked
      enzyme displays improved thermostability, particularly when combined with
      previously described mutations that enhance stability (T172R-G173Q). The newly
      modified enzyme yielded an extremely stable form of CocE (CCRQ-CocE) that
      retained greater than 90% of its activity after 41 days at 37 degrees C,
      representing an improvement of more than 4700-fold over the wild-type enzyme.
      CCRQ-CocE could also be modified by polyethylene glycol (PEG) polymers, which
      improved its in vivo residence time from 24 to 72 h, as measured by a cocaine
      lethality assay, by self-administration in rodents, and by measurement of
      inhibition of cocaine-induced cardiovascular effects in rhesus monkeys. PEG-CCRQ
      elicited negligible immune response in rodents. Subunit stabilization and
      PEGylation has thus produced a potential protein therapeutic with markedly higher
      stability both in vitro and in vivo.

PMID- 21890750
TI  - Effectiveness of antibiotic-lock therapy for long-term catheter-related
      bacteremia due to Gram-negative bacilli: a prospective observational study.
AB  - A prospective observational study evaluated the effectiveness of combining
      antibiotic-lock therapy and systemic antibiotics for Gram-negative bacilli long
      term catheter-related bacteremia. In 46 uncomplicated episodes, the most
      frequently isolated microorganisms were Pseudomonas aeruginosa (15), Enterobacter
      cloacae (12), Escherichia coli (10), and Klebsiella spp. (8). Cure was achieved
      in 95% of cases.

PMID- 21890752
TI  - Plasmodium knowlesi: An Overlooked Italian Discovery?

PMID- 21890751
TI  - Viremia copy-years predicts mortality among treatment-naive HIV-infected patients
      initiating antiretroviral therapy.
AB  - BACKGROUND: Cross-sectional plasma human immunodeficiency virus (HIV) viral load
      (VL) measures have proven invaluable for clinical and research purposes. However,
      cross-sectional VL measures fail to capture cumulative plasma HIV burden
      longitudinally. We evaluated the cumulative effect of exposure to HIV replication
      on mortality following initiation of combination antiretroviral therapy (ART).
      METHODS: We included treatment-naive HIV-infected patients starting ART from 2000
      to 2008 at 8 Center for AIDS Research Network of Integrated Clinical Systems
      sites. Viremia copy-years, a time-varying measure of cumulative plasma HIV
      exposure, were determined for each patient using the area under the VL curve.
      Multivariable Cox models were used to evaluate the independent association of
      viremia copy-years for all-cause mortality. RESULTS: Among 2027 patients
      contributing 6579 person-years of follow-up, the median viremia copy-years was
      5.3 log10 copy * y/mL (interquartile range: 4.9-6.3 log10 copy * y/mL), and 85
      patients (4.2%) died. When evaluated separately, viremia copy-years (hazard ratio
      [HR] = 1.81 per log10 copy * y/mL; 95% confidence interval [CI], 1.51-2.18 per
      log(10) copy * y/mL), 24-week VL (1.74 per log10 copies/mL; 95% CI, 1.48-2.04 per
      log10 copies/mL), and most recent VL (HR = 1.89 per log10 copies/mL; 95% CI: 1.63
      2.20 per log10 copies/mL) were associated with increased mortality. When
      simultaneously evaluating VL measures and controlling for other covariates,
      viremia copy-years increased mortality risk (HR = 1.44 per log10 copy * y/mL; 95%
      CI, 1.07-1.94 per log10 copy * y/mL), whereas no cross-sectional VL measure was
      independently associated with mortality. CONCLUSIONS: Viremia copy-years
      predicted all-cause mortality independent of traditional, cross-sectional VL
      measures and time-updated CD4+ T-lymphocyte count in ART-treated patients,
      suggesting cumulative HIV replication causes harm independent of its effect on
      the degree of immunodeficiency.

PMID- 21890753
TI  - Lack of sustained improvement in adherence or viral load following a directly
      observed antiretroviral therapy intervention.
AB  - BACKGROUND: Methadone clinic-based directly observed antiretroviral therapy (DOT)
      has been shown to be more efficacious for improving adherence and suppressing
      human immunodeficiency virus (HIV) load than antiretroviral self-administration.
      We sought to determine whether the beneficial effects of DOT remain after DOT is
      discontinued. METHODS: We conducted a post-trial cohort study of 65 HIV-infected
      opioid-dependent adults who had completed a 24-week randomized controlled trial
      of methadone clinic-based DOT versus treatment as usual (TAU). For 12 months
      after DOT discontinuation, we assessed antiretroviral adherence using monthly
      pill counts and electronic monitors. We also assessed viral load at 3, 6, and 12
      months after DOT ended. We examined differences between DOT and TAU in (1)
      adherence, (2) viral load, and (3) proportion of participants with viral load of
      <75 copies/mL. RESULTS: At trial end, adherence was higher among DOT participants
      than among TAU participants (86% and 54%, respectively; P < .001), and more DOT
      participants than TAU participants had viral loads of <75 copies/mL (71% and 44%,
      respectively; P = .03). However, after DOT ended, differences in adherence
      diminished by 1 month (55% for DOT vs 48% for TAU; P = .33) and extinguished
      completely by 3 months (49% for DOT vs 50% for TAU; P = .94). Differences in
      viral load between DOT and TAU disappeared by 3 months after the intervention,
      and the proportion of DOT participants with undetectable viral load decreased
      steadily after DOT was stopped until there was no difference (36% for DOT and 34%
      for TAU; P = .92). CONCLUSIONS: Because the benefits of DOT for adherence and
      viral load among HIV-infected methadone patients cease after DOT is stopped,
      methadone-based DOT should be considered a long-term intervention.

PMID- 21890754
TI  - Infections in patients with hematologic neoplasms and hematopoietic stem cell
      transplantation: neutropenia, humoral, and splenic defects.
AB  - Infections are common in patients with hematologic neoplasms and following
      allogeneic hematopoietic transplantation. Neutropenia and defects in adaptive B
      cell-mediated immunity and/or lack of splenic function predispose patients to a
      host of diverse and often serious infections. It is important to recognize that
      patients who undergo treatment for hematologic neoplasms may have mixed immune
      defects, and their vulnerability to infection may continue to change, in part as
      a reflection of the dynamic developments in the practice of oncology. The main
      obstacle in providing targeted, evidence-based antimicrobial treatment is the
      unpredictable results of even the new generation of diagnostic assays. A definite
      diagnosis for most end-organ opportunistic diseases requires tissue samples that
      are seldom available. Because immune defects may coexist, empirical therapy is
      directed toward a wide spectrum of pathogens. Real-time information about innate
      and adaptive immune functions and the role of acute and chronic phase molecules
      may improve target-specific therapy.

PMID- 21890755
TI  - How do centres begin the process to prevent contrast-induced acute kidney injury:
      a report from a new regional collaborative.
AB  - OBJECTIVES: This study evaluates the variation in practice patterns associated
      with contrast-induced acute kidney injury (CI-AKI) and identifies clinical
      practices that have been associated with a reduction in CI-AKI. Background CI-AKI
      is recognised as a complication of invasive cardiovascular procedures and is
      associated with cardiovascular events, prolonged hospitalisation, end-stage renal
      disease, and all-cause mortality. Reducing the risk of CI-AKI is a patient safety
      objective set by the National Quality Forum. METHODS: This study prospectively
      collected quantitative and qualitative data from 10 centres, which participate in
      the Northern New England Cardiovascular Disease Study Group PCI Registry.
      Quantitative data were collected from the PCI Registry. Qualitative data were
      obtained through clinical team meetings to map care processes related to CI-AKI
      and focus groups to understand attitudes towards CI-AKI prophylaxis. Fixed and
      random effects modelling were conducted to test the differences across centres.
      RESULTS: Significant variation in rates of CI-AKI were found across 10 medical
      centres. Both fixed effects and mixed effects logistic regression demonstrated
      significant variability across centres, even after adjustment for baseline
      covariates (p<0.001 for both modelling approaches). Patterns were found in
      reported processes and clinical leadership that were attributable to centres with
      lower rates of CI-AKI. These included reducing nil by mouth (NPO) time to 4 h
      prior to case, and standardising volume administration protocols in combination
      with administering three to four high doses of N-acetylcysteine (1200 mg) for
      each patient. CONCLUSIONS: These data suggest that clinical leadership and
      institution-focused efforts to standardise preventive practices can help reduce
      the incidence of CI-AKI.

PMID- 21890757
TI  - Exploring situational awareness in diagnostic errors in primary care.
AB  - OBJECTIVE: Diagnostic errors in primary care are harmful but poorly studied. To
      facilitate the understanding of diagnostic errors in real-world primary care
      settings that use electronic health records (EHRs), this study explored the use
      of the situational awareness (SA) framework from aviation human factors research.
      METHODS: A mixed-methods study was conducted involving reviews of EHR data
      followed by semi-structured interviews of selected providers from two
      institutions in the USA. The study population included 380 consecutive patients
      with colorectal and lung cancers diagnosed between February 2008 and January
      2009. Using a pre-tested data collection instrument, trained physicians
      identified diagnostic errors, defined as lack of timely action on one or more
      established indications for diagnostic work-up for lung and colorectal cancers.
      Twenty-six providers involved in cases with and without errors were interviewed.
      Interviews probed for providers' lack of SA and how this may have influenced the
      diagnostic process. RESULTS: Of 254 cases meeting inclusion criteria, errors were
      found in 30 of 92 (32.6%) lung cancer cases and 56 of 167 (33.5%) colorectal
      cancer cases. Analysis of interviews related to error cases revealed evidence of
      lack of one of four levels of SA applicable to primary care practice: information
      perception, information comprehension, forecasting future events, and choosing
      appropriate action based on the first three levels. In cases without error,
      application of the SA framework provided insight into processes involved in
      attention management. CONCLUSIONS: A framework of SA can help analyse and
      understand diagnostic errors in primary care settings that use EHRs.

PMID- 21890762
TI  - Diagnostic accuracy of real-time polymerase chain reaction in detection of
      Clostridium difficile in the stool samples of patients with suspected Clostridium
      difficile Infection: a meta-analysis.
AB  - BACKGROUND: Current detection methods for Clostridium difficile infection (CDI)
      can be time-consuming and have variable sensitivities. Real-time polymerase chain
      reaction (PCR) may allow earlier and more accurate diagnosis of CDI than other
      currently available diagnostic tests. A meta-analysis was performed to determine
      the diagnostic accuracy of real-time PCR. METHODS: We searched MEDLINE
      (Pubmed/Ovid) and 4 other online electronic databases (1995-2010) to identify
      diagnostic accuracy studies that compared PCR with cell culture cytotoxicity
      neutralization assay (CCCNA) or anaerobic toxigenic culture (TC) of C. difficile.
      Screening for inclusion, data extraction, and quality assessment were carried out
      independently by 2 investigators and disagreements resolved. Data were combined
      by means of a random-effects model, and summary receiver operating characteristic
      curves and diagnostic odds ratios were calculated. RESULTS: Nineteen studies
      (7392 samples) met our inclusion criteria. The overall mean sensitivity of PCR
      was 90% (95% confidence interval [CI]: 88%-91%), specificity 96% (CI: 96%-97%),
      positive likelihood ratio 26.89 (CI: 20.81-34.74), negative likelihood ratio 0.11
      (CI: .08-.15), diagnostic odds ratio 278.23 (CI: 213.56-362.50), and area under
      the curve 0.98 (CI: .98-.99). Test accuracy depended on the prevalence of C.
      difficile but not on the reference test used. At C. difficile prevalence of <10%,
      10%-20% and >20% the positive predictive value and the negative predictive value
      were 71%, 79%, 93% and 99%, 98% and 96%, respectively. CONCLUSIONS: Real-time PCR
      has a high sensitivity and specificity to confirm CDI. Overall diagnostic
      accuracy is variable and depends on CDI prevalence.

PMID- 21890763
TI  - Liposomal amphotericin B for visceral leishmaniasis in human immunodeficiency
      virus-coinfected patients: 2-year treatment outcomes in Bihar, India.
AB  - BACKGROUND: Reports on treatment outcomes of visceral leishmaniasis (VL)-human
      immunodeficiency virus (HIV) coinfection in India are lacking. To our knowledge,
      none have studied the efficacy of liposomal amphotericin B in VL-HIV coinfection.
      We report the 2-year treatment outcomes of VL-HIV-coinfected patients treated
      with liposomal amphotericin B followed by combination antiretroviral treatment
      (cART) in Bihar, India. METHODS: The study included all patients with newly
      diagnosed VL-HIV coinfection and initiating treatment with liposomal amphotericin
      B (20-25 mg/kg in 4-15 days) between July 2007 and September 2010. Kaplan-Meier
      estimates of the cumulative incidence of death/treatment failure were calculated.
      RESULTS: Fifty-five patients were included (83.6% male; median age, 35 years; 62%
      migrant laborers; median follow-up, 1 year). The median CD4 cell count at VL
      diagnosis was 66 cells/MUL (interquartile range, 38-112). Twenty-seven patients
      (49.1%) presented with VL relapse of VL. The overall tolerance of liposomal
      amphotericin B was excellent, with no interrupted treatment. Survival by 1 and 2
      years after VL treatment was estimated at 85.5%. No patients had initial
      treatment failure. The probabilities of VL relapse were 0%, 8.1%, and 26.5% at
      0.5, 1, and 2 years after VL treatment, respectively; relapse rates were similar
      for primary VL and VL relapse. CD4 counts <200 cells/MUL at 6 months after cART
      initiation were predictive of subsequent relapse. The mean CD4 cell counts at 6
      and 24 months after cART initiation were 187 and 261 cells/MUL, respectively. The
      rate for retention in HIV care was 83.6%. CONCLUSIONS: Good long-term survival
      and retention rates were obtained for VL-HIV-coinfected patients treated with
      liposomal amphotericin B and cART. Although the initial VL treatment response was
      excellent, VL relapse within 2 years remained frequent.

PMID- 21890766
TI  - Executive summary: the management of community-acquired pneumonia in infants and
      children older than 3 months of age: clinical practice guidelines by the
      Pediatric Infectious Diseases Society and the Infectious Diseases Society of
      America.
AB  - Evidenced-based guidelines for management of infants and children with community
      acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians
      and investigators representing community pediatrics, public health, and the
      pediatric specialties of critical care, emergency medicine, hospital medicine,
      infectious diseases, pulmonology, and surgery. These guidelines are intended for
      use by primary care and subspecialty providers responsible for the management of
      otherwise healthy infants and children with CAP in both outpatient and inpatient
      settings. Site-of-care management, diagnosis, antimicrobial and adjunctive
      surgical therapy, and prevention are discussed. Areas that warrant future
      investigations are also highlighted.

PMID- 21890768
TI  - Outpatient antibiotic use in the United States: time to "get smarter".

PMID- 21890767
TI  - Outpatient antibiotic prescribing and nonsusceptible Streptococcus pneumoniae in
      the United States, 1996-2003.
AB  - BACKGROUND: Streptococcus pneumoniae infections have become increasingly
      complicated and costly to treat with the spread of antibiotic resistance. We
      evaluated the relationship between antibiotic prescribing and nonsusceptibility
      among invasive pneumococcal disease (IPD) isolates. METHODS: Outpatient
      antibiotic prescription data for penicillins, cephalosporins, macrolides, and
      trimethoprim-sulfamethoxazole were abstracted from the IMS Health Xponent
      database to calculate the annual number of prescriptions per capita. We analyzed
      IPD data from 7 of the Centers for Disease Control and Prevention's Active
      Bacterial Core surveillance sites (population, 18.6 million) for which data were
      available for the entire time period under study (1996-2003). Logistic regression
      models were used to assess whether sites with high antibiotic prescribing rates
      had a high proportion of nonsusceptible and serotype 19A IPD. RESULTS: Yearly
      prescribing rates during the period 1996-2003 for children <5 years of age
      decreased by 37%, from 4.23 to 2.68 prescriptions per capita per year (P < .001),
      and those for persons >=5 years of age decreased by 42%, from 0.98 to 0.57
      prescriptions per capita per year (P < .001); increases in azithromycin
      prescribing were noted for both groups. Sites with high rates of antibiotic
      prescribing had a higher proportion of IPD nonsusceptibility than did low
      prescribing sites (P = .003 for penicillin, P < .001 for every other antibiotic
      class). Cephalosporin and macrolide prescribing were associated with penicillin
      and multidrug nonsusceptibility and serotype 19A IPD (P < .001). CONCLUSIONS: In
      sites where antibiotic prescribing is high, the proportion of nonsusceptible IPD
      is also high, suggesting that local prescribing practices contribute to local
      resistance patterns. Cephalosporins and macrolides seem to be selecting for
      penicillin- and multidrug-resistant pneumococci, as well as serotype 19A IPD.
      Antibiotic use is a major factor contributing to the spread of antibiotic
      resistance; strategies to reduce antibiotic resistance should continue to include
      judicious use of antibiotics.

PMID- 21890769
TI  - Antimicrobial use: a risk factor or a protective factor for acquiring
      campylobacteriosis?
AB  - BACKGROUND: It is well acknowledged that the use of antimicrobial drugs in food
      animals leads to antimicrobial drug resistance in foodborne bacteria such as
      Campylobacter; however, the role of human antimicrobial usage is much less
      investigated. The aim of this study was to quantify the odds of
      campylobacteriosis conferred by human consumption of fluoroquinolones and
      macrolides. METHODS: We conducted a registry-based retrospective case-control
      study on 31 669 laboratory-confirmed cases of campylobacteriosis between 1999 and
      2005 in Denmark. Data were obtained from several Danish databases: the National
      Registry of Enteric Pathogens, the Danish Civil Registration System, the Danish
      National Prescription Database, and the Integrated Database on Labor Market
      Research. Odds ratios (OR) for campylobacteriosis were calculated by conditional
      logistic regression. RESULTS: The risk of campylobacteriosis was reduced 1 month
      after exposure to macrolides (OR, 0.72; 95% confidence interval [CI], 0.56-0.92).
      Macrolide exposure 1 month to 2 years before infection was associated with an
      increased risk of a Campylobacter diagnosis (OR, 1.5; 95% CI, 1.4-1.6). A history
      of fluoroquinolone use was also associated with increased risk (OR, 2.5; 95% CI,
      1.8-3.5). This risk was higher for resistant isolates than for susceptible ones.
      CONCLUSIONS: Treatment with macrolides may protect against Campylobacter
      infection for a limited period of time, possibly due to the antibacterial effects
      of the drug or its metabolites. Fluoroquinolone treatment confers increased risk,
      probably due to a combination of competitive and selective effects, similar to
      what has been observed for nontyphoid Salmonella infection.

PMID- 21890770
TI  - Behavior change strategies to influence antimicrobial prescribing in acute care:
      a systematic review.
AB  - BACKGROUND: Antimicrobial use in acute care is widely reported to be suboptimal.
      Inappropriate use of antimicrobials is a major contributing factor to the
      emergence of multidrug resistance and health care-associated infection.
      Addressing prescribing behavior is a key component of antimicrobial stewardship.
      METHODS: We performed a novel systematic review of both qualitative and
      quantitative literature on antimicrobial prescribing behavior in acute care. We
      assessed the extent to which behavioral sciences and social marketing were used
      and whether this could be related to the effectiveness of reported outcomes.
      MEDLINE, Excerpta Medica Database (EMBASE), Applied Social Sciences Index and
      Abstracts (ASSIA), Business Source Complete, The Cochrane Library, PsychInfo,
      Database of Abstracts of Reviews of Effectiveness (DARE) and Health Management
      Information Consortium (HMIC) were searched for studies undertaken during the
      period January 1999-April 2011 and published in English. RESULTS: Five
      qualitative and 5 quantitative studies met the quality criteria. Qualitative
      studies highlight the predominant influence of social norms, attitudes, and
      beliefs on antimicrobial prescribing behavior. Quantitative studies reporting
      interventions to optimize antimicrobial prescribing behavior do not use
      theoretical science or primary research to inform the design and choice of the
      interventions deployed. CONCLUSIONS: Despite qualitative evidence demonstrating
      the impact of behavioral determinants and social norms on prescribing, these
      influences are not given due consideration in the design and evaluation of
      interventions. To ensure a better understanding of prescribing behaviors and to
      improve the quality of interventions and research in this area, the incorporation
      and application of behavioral sciences supported by appropriate multidisciplinary
      collaboration is recommended.

PMID- 21890771
TI  - Massive increase, spread, and exchange of extended spectrum beta-lactamase
      encoding genes among intestinal Enterobacteriaceae in hospitalized children with
      severe acute malnutrition in Niger.
AB  - BACKGROUND: From the time of CTX-M emergence, extended-spectrum beta-lactamase
      producing enterobacteria (ESBL-E) have spread worldwide in community settings as
      well as in hospitals, particularly in developing countries. Although their
      dissemination appears linked to Escherichia coli intestinal carriage, precise
      paths of this dynamic are largely unknown. METHODS: Children from a pediatric
      renutrition center were prospectively enrolled in a fecal carriage study.
      Antibiotic exposure was recorded. ESBL-E strains were isolated using selective
      media from fecal samples obtained at admission and, when negative, also at
      discharge. ESBL-encoding genes were identified, their environments and plasmids
      were characterized, and clonality was assessed with polymerase chain reaction
      based methods and pulsed-field gel electrophoresis for E. coli and Klebsiella
      pneumoniae. E. coli strains were subjected to multilocus sequence typing.
      RESULTS: The ESBL-E carriage rate was 31% at admission in the 55 children
      enrolled. All children enrolled received antibiotics during hospitalization.
      Among the ESBL-E-negative children, 16 were resampled at discharge, and the
      acquisition rate was 94%. The bla(CTX-M-15) gene was found in >90% of the
      carriers. Genetic environments and plasmid characterization evidenced the roles
      of a worldwide, previously described, multidrug-resistant region and of IncF
      plasmids in CTX-M-15 E. coli dissemination. Diversity of CTX-M-15-carrying
      genetic structures and clonality of acquired ESBL E. coli suggested horizontal
      genetic transfer and underlined the potential of some ST types for nosocomial
      cross-transmission. CONCLUSIONS: Cross-transmission and high selective pressure
      lead to very high acquisition of ESBL-E carriage, contributing to dissemination
      in the community. Strict hygiene measures as well as careful balancing of benefit
      risk ratio of current antibiotic policies need to be reevaluated.

PMID- 21890772
TI  - Risk factors for surgical site infections following spinal fusion procedures: a
      case-control study.
AB  - BACKGROUND: Spinal fusion procedures are associated with a significant rate of
      surgical site infection (SSI) (1%-12%). The goal of this study was to identify
      modifiable risk factors for spinal fusion SSIs at a large tertiary care center.
      METHODS: A retrospective, case-control (1:3 ratio) analysis of SSIs following
      posterior spine fusion procedures was performed over a 1-year period. Clinical
      and surgical data were collected through electronic database and chart review.
      Variables were evaluated by univariate analysis and multivariable logistic
      regression. RESULTS: In total, 57 deep SSIs were identified out of 1587
      procedures (3.6%). Infections were diagnosed a mean of 13.5 +/- 8 days
      postprocedure. Staphylococcus aureus was the predominant pathogen (63%); 1/3 of
      these isolates were methicillin resistant. Significant patient risk factors for
      infection by univariate analysis included ASA score >2 and male gender. Among
      surgical variables, infected cases had significantly higher proportions of staged
      procedures and thoracic level surgeries and had a greater number of vertebrae
      fused. Notably, infected fusion procedures had a longer duration of closed
      suction drains than controls (5.1 +/- 2 days vs 3.4 +/- 1 day, respectively; P <
      .001). Drain duration (unit odds ratio [OR], 1.6 per day drain present; 95%
      confidence interval [CI], 1.3-1.9), body mass index (OR, 1.1; 95% CI, 1.0-1.1),
      and male gender (OR, 2.7; 95% CI, 1.4-5.6) were significant risk factors in the
      multivariate analysis. CONCLUSIONS: Prolonged duration of closed suction drains
      is a strong independent risk factor for SSI following instrumented spinal fusion
      procedures. Therefore, removing drains as early as possible may lower infection
      rates.

PMID- 21890773
TI  - High-dose oral fluconazole therapy effective for cutaneous leishmaniasis due to
      Leishmania (Vianna) braziliensis.
AB  - We report for the first time the successful use of fluconazole to treat cutaneous
      leishmaniasis due to Leishmania braziliensis. We used escalating doses from 5 to
      8 mg/kg per day. At a dose of 5 mg/kg per day, 75% patients were cured, and at 8
      mg/kg per day, the cure rate was 100%. Fluconazole was well tolerated.

PMID- 21890774
TI  - Pervasive pneumatosis in a patient on immunosuppressive agents.

PMID- 21890775
TI  - Defining bloodstream infections related to central venous catheters in patients
      with cancer: a systematic review.
AB  - The objective of this review was to determine whether consistent definitions were
      used in published studies of bloodstream infections due to central venous
      catheters in patients with cancer (ie, catheter-related or catheter-associated
      bloodstream infections). Review of 191 studies reporting catheter-related or
      catheter-associated bloodstream infections in patients with cancer revealed a
      lack of uniformity in these definitions. We grouped definitions by type, with 39
      articles failing to cite or report a definition. Definitions included those of
      the Centers for Disease Control and Prevention (n = 39) and the Infectious
      Diseases Society of America (n = 18). The criteria included in the definitions in
      studies were also tabulated. Clinical manifestations were frequently included.
      Definitions used have been highly variable; comparability of risk factors,
      incidence, management, and outcomes of such infections is difficult to achieve
      across studies. Future research should focus on development of a common
      definition of catheter-related and catheter-associated bloodstream infections for
      both adults and children with cancer.

PMID- 21890776
TI  - Efficacy and safety of once-daily nevirapine- or efavirenz-based antiretroviral
      therapy in HIV-associated tuberculosis: a randomized clinical trial.
AB  - BACKGROUND: Nevirapine (NVP) can be safely and effectively administered once
      daily but has not been assessed in human immunodeficiency virus (HIV)-infected
      patients with tuberculosis (TB). We studied the safety and efficacy of once-daily
      NVP, compared with efavirenz (EFV; standard therapy); both drugs were
      administered in combination with 2 nucleoside reverse-transcriptase inhibitors.
      METHODS: An open-label, noninferiority, randomized controlled clinical trial was
      conducted at 3 sites in southern India. HIV-infected patients with TB were
      treated with a standard short-course anti-TB regimen (2EHRZ(3)/4RH(3); [2 months
      of Ethambutol, Isoniazid, Rifampicin, Pyrazinamide / 4 months of Isoniazid and
      Rifampicin] thrice weekly) and randomized to receive once-daily EFV at a dose of
      600 mg or NVP at a dose of 400 mg (after 14 days of 200 mg administered once
      daily) with didanosine 250/400 mg and lamivudine 300 mg after 2 months. Sputum
      smears and mycobacterial cultures were performed every month. CD4+ cell count,
      viral load, and liver function test results were monitored periodically. Primary
      outcome was a composite of death, virological failure, default, or serious
      adverse event (SAE) at 24 weeks. Both intent-to-treat and per protocol analyses
      were done, and planned interim analyses were performed. RESULTS: A total of 116
      patients (75% [87 patients] of whom had pulmonary TB), with a mean age of 36
      years, a median CD4+ cell count of 84 cells/mm(3), and a median viral load of 310
      000 copies/mL, were randomized. At 24 weeks, 50 of 59 patients in the EFV group
      and 37 of 57 patients in the NVP group had virological suppression (P = .024).
      There were no deaths, 1 SAE, and 5 treatment failures in the EFV arm, compared
      with 5 deaths, 2 SAEs, and 10 treatment failures in the NVP arm. The trial was
      halted by the data and safety monitoring board at the second interim analysis.
      Favorable TB treatment outcomes were observed in 93% of the patients in the EFV
      arm and 84% of the patients in the NVP arm (P = .058). CONCLUSIONS: Compared with
      a regimen of didanosine, lamivudine, and EFV, a regimen of once-daily didanosine,
      lamivudine, and NVP was inferior and was associated with more frequent virologic
      failure and death. Clinical Trials Registration. NCT00332306.

PMID- 21890777
TI  - Incarceration predicts virologic failure for HIV-infected injection drug users
      receiving antiretroviral therapy.
AB  - BACKGROUND: Incarceration may lead to interruptions in antiretroviral therapy
      (ART) for persons receiving treatment for human immunodeficiency virus (HIV)
      infection. We assessed whether incarceration and subsequent release were
      associated with virologic failure for injection drug users (IDUs) who were
      previously successfully treated with ART. METHODS: ALIVE is a prospective,
      community-based cohort study of IDUs in Baltimore, Maryland. IDUs receiving ART
      during 1998-2009 who successfully achieved an HIV RNA level below the limit of
      detection (<400 copies/mL) were followed up for development of virologic failure
      at the subsequent semiannual study visit. Logistic regression with generalized
      estimating equations was used to assess whether incarceration was independently
      associated with virologic failure. RESULTS: Of 437 HIV-infected IDUs who achieved
      undetectable HIV RNA for at least one study visit, 69% were male, 95% were
      African-American, and 40% reported at least one incarceration during follow-up.
      Virologic failure occurred at 26.3% of visits after a median of 6 months since
      achieving undetectable HIV RNA. In multivariate analysis accounting for
      demographic characteristics, drug use, and HIV disease stage, brief incarceration
      was strongly associated with virologic failure (adjusted odds ratio, 7.7; 95%
      confidence interval, 3.0-19.7), although incarceration lasting >30 days was not
      (odds ratio, 1.4; 95% confidence interval, .8-2.6). CONCLUSIONS: Among IDUs
      achieving viral suppression while receiving ART, virologic failure occurred with
      high frequency and was strongly associated with brief incarceration. Efforts
      should be made to ensure continuity of care both during and after incarceration
      to improve treatment outcomes and prevent viral resistance in this vulnerable
      population.

PMID- 21890778
TI  - Deep V3 sequencing for HIV type 1 tropism in treatment-naive patients: a
      reanalysis of the MERIT trial of maraviroc.
AB  - BACKGROUND: Deep sequencing is a highly sensitive technique that can detect and
      quantify the proportion of non-R5 human immunodeficiency virus (HIV) variants,
      including small minorities, that may emerge and cause virologic failure in
      patients who receive maraviroc-containing regimens. We retrospectively tested the
      ability of deep sequencing to predict response to a maraviroc-containing regimen
      in the Maraviroc versus Efavirenz in Treatment-Naive Patients (MERIT) trial.
      Results were compared with those obtained using the Enhanced Sensitivity Trofile
      Assay (ESTA), which is widely used in clinical practice. METHODS: Screening
      plasma samples from treatment-naive patients who received maraviroc and efavirenz
      in the MERIT trial were assessed. Samples were extracted, and the V3 region of
      HIV type 1 glycoprotein 120 was amplified in triplicate and combined in equal
      quantities before sequencing on a Roche/454 Genome Sequencer-FLX (n = 859).
      Tropism was inferred from third variable (V3) sequences, with samples classified
      as non-R5 if >=2% of the viral population scored <=3.5 using geno2pheno. RESULTS:
      Deep sequencing distinguished between responders and nonresponders to maraviroc.
      Among patients identified as having R5-HIV by deep sequencing, 67% of maraviroc
      recipients and 69% of efavirenz recipients had a plasma viral load <50 copies/mL
      at week 48, similar to the ESTA results: 68% and 68%, respectively. CONCLUSIONS:
      Reanalysis of the MERIT trial using deep V3 loop sequencing indicates that, had
      patients originally been screened using this method, the maraviroc arm would have
      likely been found to be noninferior to the efavirenz arm.

PMID- 21890780
TI  - Prevention of intravascular central venous catheter-related infections: 0.5%
      concentration of chlorhexidine preparation with alcohol for skin preparation and
      femoral vein for renal replacement therapy.

PMID- 21890783
TI  - A comment on Marschall et Al.

PMID- 21890784
TI  - Chronic Q fever: relevance of serology.

PMID- 21890785
TI  - Clinical outcomes of xeno-free autologous cultivated limbal epithelial
      transplantation: a 10-year study.
AB  - PURPOSE: Ocular burns can damage the corneal epithelial stem cells located at the
      limbus. This study evaluated the efficacy of xeno-free autologous cell-based
      treatment of limbal stem cell deficiency. METHODS: This retrospective study
      included 200 patients, above 8 years of age, with clinically diagnosed unilateral
      total limbal stem cell deficiency due to ocular surface burns treated between
      2001 and 2010. A small limbal biopsy was obtained from the unaffected eye. The
      limbal epithelial cells were expanded ex vivo on human amniotic membrane for 10
      14 days using a xeno-free explant culture system. The resulting cultured
      epithelial monolayer and amniotic membrane substrate were transplanted on to the
      patient's affected eye. Postoperative corneal surface stability, visual
      improvement and complications were objectively analysed. RESULTS: A completely
      epithelised, avascular and clinically stable corneal surface was seen in 142 of
      200 (71%) eyes at a mean follow-up of 3 +/- 1.6 (range: 1-7.6) years. A two-line
      improvement in visual acuity, without further surgical intervention, was seen in
      60.5% of eyes. All donor eyes remained healthy. CONCLUSIONS: Autologous
      cultivated limbal epithelial transplantation using a xeno-free explant culture
      technique was effective in long-term restoration of corneal epithelial stability
      and improvement of vision in eyes with ocular surface burns.

PMID- 21890787
TI  - Predictive factors of resolved retinal fluid after intravitreal ranibizumab for
      polypoidal choroidal vasculopathy.
AB  - BACKGROUND/AIMS: To investigate the predictive factors for the resolution of
      retinal fluid after intravitreal injections of ranibizumab (IVRs) for polypoidal
      choroidal vasculopathy (PCV). METHODS: Forty-seven eyes of 45 patients with
      symptomatic PCV received 0.5 mg of IVR monthly for 3 months. One month after the
      third IVR, the presence of dry macula, defined as absence of retinal fluid as
      detected by the use of optical coherence tomography, was retrospectively
      evaluated and correlated with clinical characteristics at baseline. Most of the
      eyes were followed for over 6 months. RESULTS: Of the 47 eyes, 31 eyes (66%)
      achieved the dry macula along with increased best-corrected visual acuity (BCVA)
      (0.64 to 0.46 logarithm of the minimum angle of resolution units, p<0.0001),
      while the other 16 eyes without dry macula showed no significant change of BCVA.
      Univariate analyses of the baseline characteristics identified the smaller size
      of the largest polyp (p=0.0008) and the absence of serous or haemorrhagic pigment
      epithelial detachment (p=0.045) as predictive factors for the dry macula.
      Multivariate logistic regression found the independent predictor for the dry
      macula to be the smaller size of the largest polyp (p=0.001). No severe systemic
      or ocular adverse events were observed. CONCLUSIONS: IVR may be helpful for
      resolution of retinal fluid and increased BCVA in the short term, but larger
      polyps and pigment epithelial detachments at baseline may be negative prognostic
      factors for a therapeutic response. Further studies are needed to clarify the
      long-term efficacy of IVR for PCV.

PMID- 21890786
TI  - The oil spill in ageing Bruch membrane.
AB  - Ageing is the largest risk factor for age-related macular degeneration (AMD), and
      soft drusen and basal linear deposits are lipid-rich extracellular lesions
      specific to AMD. Oil red O binding neutral lipid represents a major age-related
      deposition in the Bruch membrane (BrM) and the first identified druse component.
      Decades after these seminal observations, a natural history of neutral lipid
      deposition has been articulated and a biochemical model proposed. Results
      obtained with multiple biochemical, histochemical, and ultrastructural methods,
      and supported indirectly by epidemiology, suggest that the RPE secretes
      apolipoprotein B (apoB)-lipoprotein particles of unusual composition into BrM,
      where they accumulate with age eventually forming a lipid wall, a precursor of
      basal linear deposit. The authors propose that constituents of these lesions
      interact with reactive oxygen species to form pro-inflammatory peroxidised lipids
      that elicit neovascularisation. Here, the authors summarise key evidence
      supporting both accumulation of BrM lipoproteins leading to lesion formation and
      lipoprotein production by the RPE. The authors update their model with genetic
      associations between AMD and genes historically associated with plasma HDL
      metabolism, and suggest future directions for research and therapeutic strategies
      based on an oil-spill analogy.

PMID- 21890788
TI  - Do shapes and dimensions of scleral flap and sclerostomy influence aqueous
      outflow in trabeculectomy? A finite element simulation approach.
AB  - BACKGROUND/AIM: This study aimed to provide an objective assessment of the
      effects on the aqueous outflow rate of various geometries of the scleral flap and
      sclerostomy created in trabeculectomy. METHOD: Computer-based models and
      simulations of this surgical procedure were used to investigate the relative
      effects of various shapes and dimensions of scleral flap and sclerostomy on the
      aqueous outflow. RESULT: In these computer simulations, increasing scleral flap
      size was found to be associated with an increase of 48.55% in aqueous egress. In
      addition, a square scleral flap increased the aqueous drainage by 36.26% compared
      with a triangular flap of equivalent flap area. Surprisingly, our simulation
      results showed that a smaller semicircular sclerostomy improved aqueous drainage
      by up to 33.00%, while a semicircular sclerostomy, compared with a circular
      sclerostomy, led to a further 6.16% increase in aqueous outflow. Decreasing flap
      thickness beyond half-thickness caused an additional increase in aqueous outflow.
      However, clinically the flap should not be thinner than half the thickness of the
      sclera as this may result in hypotony. CONCLUSION: These simulations indicate
      that the optimal flow rate through operation site will be achieved in
      trabeculectomy using a square scleral flap with a large flap-to-sclerostomy
      ratio.

PMID- 21890789
TI  - Increased risk of schizophrenia from additive interaction between infant motor
      developmental delay and obstetric complications: evidence from a population-based
      longitudinal study.
AB  - OBJECTIVE: Obstetric complications and developmental delay are well-established
      risk factors for schizophrenia. The authors investigated whether these risk
      factors interact in an additive manner to further increase risk for
      schizophrenia. METHOD: The study population encompassed all individuals born in
      Helsinki between 1962 and 1969 who had developmental records archived in the
      Helsinki City Archives. Through linkage between the Finnish Population Register,
      the Finnish Hospital Discharge Register, and the Child Health Archives, child
      health cards were traced for 189 individuals who had received a diagnosis of
      schizophrenia and 189 healthy comparison subjects, individually matched to case
      subjects on gender and year of birth. Child health cards from the Child Health
      Archives contain detailed prospective developmental data from birth as well as an
      indicator of fetal distress, as measured by the Apgar score. Detailed
      developmental data from the first year of life were extracted. RESULTS: Delayed
      attainment of milestones in infancy significantly increased the risk of later
      development of schizophrenia in a dose-response manner. There was no significant
      main effect of obstetric complications on risk for schizophrenia and no
      significant association between obstetric complications and subsequent
      developmental delay. However, the additive effect of obstetric complications and
      delayed attainment of developmental milestones significantly increased the risk
      of schizophrenia beyond that associated with each factor independently (odds
      ratio=4.6, 95% confidence interval=1.3-17.2). CONCLUSIONS: These data provide
      evidence that underlying neurodevelopmental vulnerability, as indexed by delayed
      attainment of milestones, combined with obstetric adversity significantly
      increases the risk of schizophrenia in adulthood.

PMID- 21890790
TI  - Allelic differences between Han Chinese and Europeans for functional variants in
      ZNF804A and their association with schizophrenia.
AB  - OBJECTIVE: ZNF804A is a schizophrenia risk gene that was recently identified by
      genome-wide association studies as well as subsequent replications. Although the
      results are consistent among studies in European populations, there have been
      conflicting reports in Chinese populations. The authors conducted both
      association and functional analyses to test whether ZNF804A is a risk gene for
      schizophrenia in Chinese populations. METHOD: The authors recruited two case
      control samples of independent Han Chinese (a total of 2,207 participants) from
      southwestern China. A total of six single-nucleotide polymorphisms (SNPs),
      including the key SNP (rs1344706) that showed significant association with
      schizophrenia in European populations and the other five promoter SNPs of
      ZNF804A, were tested. Based on the results of the association analysis, the
      authors performed two functional assays to test the impact of the risk SNP on
      transcriptional factor binding affinity and promoter activity. RESULTS: The SNP
      rs1344706 was not associated with schizophrenia in either of the two Han Chinese
      groups, and this result was confirmed by meta-analyses in five Han Chinese
      samples. However, the authors identified two ZNF804A promoter SNPs that were
      significantly associated with schizophrenia in both samples, and the significance
      was strengthened in the combined samples and further supported by haplotype
      analysis. The functional assays demonstrated that the risk SNP (rs359895) can
      influence Sp1 binding affinity, resulting in a higher promoter activity of the
      risk allele. CONCLUSIONS: Our results suggest that ZNF804A is a common risk gene
      for schizophrenia in world populations and that the newly identified functional
      SNP (rs359895) is likely a risk SNP for schizophrenia.

PMID- 21890791
TI  - A critical review of the first 10 years of candidate gene-by-environment
      interaction research in psychiatry.
AB  - OBJECTIVE: Gene-by-environment interaction (G*E) studies in psychiatry have
      typically been conducted using a candidate G*E (cG*E) approach, analogous to the
      candidate gene association approach used to test genetic main effects. Such cG*E
      research has received widespread attention and acclaim, yet cG*E findings remain
      controversial. The authors examined whether the many positive cG*E findings
      reported in the psychiatric literature were robust or if, in aggregate, cG*E
      findings were consistent with the existence of publication bias, low statistical
      power, and a high false discovery rate. METHOD: The authors conducted analyses on
      data extracted from all published studies (103 studies) from the first decade
      (2000-2009) of cG*E research in psychiatry. RESULTS: Ninety-six percent of novel
      cG*E studies were significant compared with 27% of replication attempts. These
      findings are consistent with the existence of publication bias among novel cG*E
      studies, making cG*E hypotheses appear more robust than they actually are. There
      also appears to be publication bias among replication attempts because positive
      replication attempts had smaller average sample sizes than negative ones. Power
      calculations using observed sample sizes suggest that cG*E studies are
      underpowered. Low power along with the likely low prior probability of a given
      cG*E hypothesis being true suggests that most or even all positive cG*E findings
      represent type I errors. CONCLUSIONS: In this new era of big data and small
      effects, a recalibration of views about groundbreaking findings is necessary.
      Well-powered direct replications deserve more attention than novel cG*E findings
      and indirect replications.

PMID- 21890792
TI  - Behavioral health insurance parity: does Oregon's experience presage the national
      experience with the Mental Health Parity and Addiction Equity Act?
AB  - OBJECTIVE: The Mental Health Parity and Addiction Equity Act of 2008 prohibits
      commercial group health plans from imposing spending and visit limitations for
      mental health and substance abuse services that are not imposed on medical
      surgical services. The act also restricts the use of managed care tools that
      apply to behavioral health benefits in ways that differ from how they apply to
      medical-surgical benefits. The only precedent for this approach is Oregon's state
      parity law, which was implemented in 2007. The goal of this study was to estimate
      the effect of Oregon's parity law on expenditures for mental health and substance
      abuse treatment services. METHOD: The authors compared expenditures for
      commercially insured individuals in four Oregon health plans from 2005 through
      2008 and a matched group of commercially insured individuals in Oregon who were
      exempt from parity. Using a difference-in-differences analysis, the authors
      analyzed the effect of comprehensive parity on spending for mental health and
      substance abuse services. RESULTS: Increases in spending on mental health and
      substance abuse services after implementation of Oregon's parity law were almost
      entirely the result of a general trend observed among individuals with and
      without parity. Expenditures per enrollee for mental health and substance abuse
      services attributable to parity were positive, but they did not differ
      significantly from zero in any of the four plans. CONCLUSIONS: Behavioral health
      insurance parity rules that place restrictions on how plans manage mental health
      and substance abuse services can improve insurance protections without
      substantial increases in total costs.

PMID- 21890794
TI  - Roles of the placenta in fetal brain development.

PMID- 21890797
TI  - The highs and lows of counting autism.

PMID- 21890793
TI  - Blood pressure and heart rate over 10 years in the multimodal treatment study of
      children with ADHD.
AB  - OBJECTIVE: It is unknown whether prolonged childhood exposure to stimulant
      medication for the treatment of attention deficit hyperactivity disorder (ADHD)
      increases the risk for developing abnormalities in blood pressure or heart rate.
      The authors examined the association between stimulant medication and blood
      pressure and heart rate over 10 years. METHOD: A total of 579 children, ages 7-9,
      were randomly assigned to 14 months of medication treatment, behavioral therapy,
      the combination of the two, or usual community treatment. The controlled trial
      was followed by naturalistic treatment with periodic assessments. Blood pressure
      and heart rate data were first analyzed with linear regression models based on an
      intent-to-treat approach, using raw data and the blood pressure categories of
      prehypertension and hypertension. Currently medicated patients were then compared
      with never or previously medicated patients. Associations between cumulative
      stimulant exposure and blood pressure or heart rate were assessed. RESULTS: No
      treatment effect on either systolic or diastolic blood pressure could be
      detected. Children who were treated with stimulants had a higher heart rate
      (mean=84.2 bpm [SD=12.4] on medication alone and mean=84.6 bpm [SD=12.2] on
      medication plus behavioral therapy) than those who were treated with behavioral
      therapy alone (mean=79.1 bpm [SD=12.0]) or those who received usual community
      treatment (mean=78.9 bpm [SD=12.9]) at the end of the 14-month controlled trial,
      but not thereafter. Stimulant medication did not increase the risk for
      tachycardia, but greater cumulative stimulant exposure was associated with a
      higher heart rate at years 3 and 8. CONCLUSIONS: Stimulant treatment did not
      increase the risk for prehypertension or hypertension over the 10-year period of
      observation. However, stimulants had a persistent adrenergic effect on heart rate
      during treatment.

PMID- 21890796
TI  - Highly variable recessive lethal or nearly lethal mutation rates during germ-line
      development of male Drosophila melanogaster.
AB  - Each cell of higher organism adults is derived from a fertilized egg through a
      series of divisions, during which mutations can occur. Both the rate and timing
      of mutations can have profound impacts on both the individual and the population,
      because mutations that occur at early cell divisions will affect more tissues and
      are more likely to be transferred to the next generation. Using large-scale
      multigeneration screening experiments for recessive lethal or nearly lethal
      mutations of Drosophila melanogaster and recently developed statistical analysis,
      we show for male D. melanogaster that (i) mutation rates (for recessive lethal or
      nearly lethal) are highly variable during germ cell development; (ii) first cell
      cleavage has the highest mutation rate, which drops substantially in the second
      cleavage or the next few cleavages; (iii) the intermediate stages, after a few
      cleavages to right before spermatogenesis, have at least an order of magnitude
      smaller mutation rate; and (iv) spermatogenesis also harbors a fairly high
      mutation rate. Because germ-line lineage shares some (early) cell divisions with
      somatic cell lineage, the first conclusion is readily extended to a somatic cell
      lineage. It is conceivable that the first conclusion is true for most (if not
      all) higher organisms, whereas the other three conclusions are widely applicable,
      although the extent may differ from species to species. Therefore, conclusions or
      analyses that are based on equal mutation rates during development should be
      taken with caution. Furthermore, the statistical approach developed can be
      adopted for studying other organisms, including the human germ-line or somatic
      mutational patterns.

PMID- 21890798
TI  - Depression, smoking, and heart disease: how can psychiatrists be effective?

PMID- 21890799
TI  - Molecular etiologies of schizophrenia: are we almost there yet?

PMID- 21890800
TI  - Switching antipsychotic medications: not enough, too often, or just right?

PMID- 21890801
TI  - Imaging a brighter future.

PMID- 21890802
TI  - Palliative psychotherapy.

PMID- 21890803
TI  - A suicidal adult in crisis: an unexpected diagnosis of autism spectrum disorder.

PMID- 21890804
TI  - An early Greek portrayal of a mad mind.

PMID- 21890805
TI  - Succinylcholine shortage and electroconvulsive therapy.

PMID- 21890806
TI  - Do all relapses in schizophrenia warrant resumption of medication?

PMID- 21890807
TI  - Determination of premenstrual symptom exacerbations.

PMID- 21890808
TI  - Safety of antipsychotics in the setting of QTc prolongation: the utility of the
      JT index.

PMID- 21890809
TI  - Medicine as combining natural and human science.
AB  - Medicine is unique in being a combination of natural science and human science in
      which both are essential. Therefore, in order to make sense of medical practice,
      we need to begin by drawing a clear distinction between the natural and the human
      sciences. In this paper, I try to bring the old distinction between the Geistes
      and Naturwissenschaften up to date by defending the essential difference between
      a realist explanatory theoretical study of nature including the body in which the
      scientist discovers the causal properties of natural kinds and the interpretive
      understanding of human beings as embodied agents which, as Charles Taylor has
      convincingly argued, requires a hermeneutic account of self-interpreting human
      practices.

PMID- 21890810
TI  - The relationships of perpetrator and victim substance use to the sexual
      aggression of rapists and child molesters.
AB  - OBJECTIVE: This study investigated substance use in rape and child molestation.
      We hypothesized that perpetrator substance use would be associated with a greater
      increase in rapists' aggression in sexual crimes compared with that of child
      molesters. We also predicted that victim substance use would be negatively
      related to both rapists and child molesters' aggression in sexual crimes. METHOD:
      The sample included 245 male rapists and 273 male child molesters who had been
      evaluated at the Massachusetts Treatment Center (MTC) between 1959 and 1991 for
      potential civil commitment. Data were obtained from offenders' archival records
      and were coded by trained research assistants on perpetrator and victim substance
      use and perpetrator aggression in sexual crimes. RESULTS: Analyses showed that
      the magnitude of the positive association between perpetrator alcohol use and
      aggression in sexual crimes did not differ between rapists and child molesters.
      In contrast, perpetrator drug use was associated with increased aggression among
      child molesters only. Victim substance use was related to increased aggression
      among rapists only. CONCLUSIONS: The results indicate that victim substance use
      and perpetrator drug use, but not perpetrator alcohol use, are differentially
      related to the aggression of rapists and child molesters in sexual crimes. Those
      findings imply that substance use may play different roles depending on offender
      type.

PMID- 21890811
TI  - Cell surface proteomics identifies glucose transporter type 1 and prion protein
      as candidate biomarkers for colorectal adenoma-to-carcinoma progression.
AB  - BACKGROUND AND OBJECTIVE: Early detection of colon adenomas at high risk of
      progression and early-stage colorectal cancer (CRC) is an effective approach to
      reduce CRC death rates. Current screening methods lack specificity as they detect
      many adenomas that will never progress to CRC. The authors aimed to identify cell
      surface protein biomarkers with extracellular domains that could be targeted for
      molecular imaging and discriminate low-risk adenomas and normal colon from high
      risk adenomas and CRC. DESIGN: Cell surface proteins of five CRC cell lines were
      biotinylated, isolated and analysed by in-depth proteomics using gel
      electrophoresis and nanoliquid chromatography coupled to tandem mass
      spectrometry. Differential expression in adenomas and CRCs was based on mRNA
      expression and verified by immunohistochemical staining of tissue microarrays.
      RESULTS: In total, 2609 proteins were identified in the cell surface fractions.
      Of these, 44 proteins were selected as promising cell surface candidate
      biomarkers for adenoma-to-carcinoma progression based on the following criteria:
      protein identification in at least four out of five cell lines, a predicted
      (trans)membrane location and increased mRNA expression in CRCs compared to
      adenomas. Increased protein expression in high-risk adenomas and CRCs compared to
      low-risk adenomas was confirmed by immunohistochemistry for glucose transporter
      type 1 (gene symbol SLC2A1; p<0.00001) and prion protein (gene symbol PRNP;
      p<0.005). CONCLUSION: This study revealed glucose transporter type 1, prion
      protein and 42 other cell surface candidate biomarkers for adenoma-to-carcinoma
      progression that could potentially serve as targets for emerging molecular
      imaging modalities like optical imaging, 19F-MRI and positron emission
      tomography.

PMID- 21890812
TI  - Intestinal permeability in coeliac disease: insight into mechanisms and relevance
      to pathogenesis.
AB  - Coeliac disease is a gut disease driven by an abnormal immune response towards
      dietary gluten in genetically susceptible individuals. Whether and, if so, how
      abnormal transport of gluten across the gut epithelium may participate in the
      pathogenesis of coeliac disease remains debatable. This paper summarises the
      interactions of gluten-derived peptides with the intestinal epithelium and
      discusses the mechanisms that control their transport across the epithelium. It
      shows how recent data point to a key role for the transcellular pathway and
      highlights the 'Trojan horse' role of secretory IgA which can hijack the
      transferrin receptor and allow the rapid translocation of intact gluten peptides
      into the mucosa. These recent findings might be useful for the design of new
      treatments.

PMID- 21890813
TI  - Constipation and recurrent abdominal distension in a 39-year-old woman with
      irritable bowel syndrome.

PMID- 21890815
TI  - Gastrointestinal and liver diseases: genetic and epigenetic markers.

PMID- 21890814
TI  - Prevention by daily soluble aspirin of colorectal adenoma recurrence: 4-year
      results of the APACC randomised trial.
AB  - BACKGROUND: Aspirin inhibits colorectal carcinogenesis. In a randomised double
      blind placebo-controlled trial, daily soluble aspirin significantly reduced
      recurrence of colorectal adenomas at 1-year follow-up. In this study the results
      of daily intake of low-dose aspirin on polyp recurrence at 4-year follow-up are
      presented. METHODS: 272 patients (naive for chronic aspirin use) with colorectal
      adenomas were randomly assigned to treatment with lysine acetylsalicylate 160
      mg/day (n=73) or 300 mg/day (n=67) or placebo (n=132) for 4 years. The primary
      endpoints were adenoma recurrence and adenomatous polyp burden at year 4,
      comparing aspirin at either dose with placebo. The same endpoints were also
      assessed at year 1 or 4 (last colonoscopy performed for each patient). RESULTS:
      At the final year 4 colonoscopy the analysis included 185 patients (55 receiving
      aspirin 160 mg/day, 47 aspirin 300 mg/day and 83 placebo). There was no
      difference in the proportion of patients with at least one recurrent adenoma
      between patients receiving aspirin at either dose and those treated with placebo
      (42/102 (41%) vs 33/83 (40%); NS) or in the adenomatous polyp burden (3.1 +/- 5.8
      mm vs 3.4 +/- 6.2 mm; NS). Also, the proportion of patients with at least one
      advanced recurrent adenoma did not differ (10/102 [corrected] (10%) in the
      aspirin group vs 7/83 (8.4%) [corrected] in the placebo group; NS). CONCLUSION:
      Daily low-dose aspirin decreased adenoma recurrence significantly at 1 year but
      not at year 4. This discrepancy might be explained by a differential effect of
      aspirin according to the natural history of the polyp. TRIAL REGISTRATION NUMBER:
      NCT 00224679.

PMID- 21890816
TI  - Long-term clinical outcome of gastric MALT lymphoma after eradication of
      Helicobacter pylori: a multicentre cohort follow-up study of 420 patients in
      Japan.
AB  - OBJECTIVE: A multicentre cohort follow-up study of a large number of patients
      with gastric mucosa-associated lymphoid tissue (MALT) lymphoma was conducted to
      elucidate the long-term outcome of the disease after Helicobacter pylori
      eradication. METHODS: 420 patients with gastric low-grade MALT lymphoma who had
      undergone successful H pylori eradication and been followed up for at least 3
      years were registered from 21 participating institutes. Responders to treatment
      were defined as patients whose post-treatment biopsies showed complete
      histological response (ChR) or probable minimal residual disease (pMRD).
      Treatment failure was defined as the status of progressive disease or lymphoma
      relapse after ChR/pMRD. RESULTS: 323 patients (77%) responded to H pylori
      eradication. A logistic regression analysis showed that absence of H pylori,
      submucosal invasion determined by endoscopic ultrasonography and t(11;18)/API2
      MALT1 were independent predictors of resistance to H pylori eradication. During
      the follow-up periods ranging from 3.0 to 14.6 years (mean 6.5 years, median 6.04
      years), the disease relapsed in 10 of 323 responders (3.1%) while progressive
      disease was found in 27 of 97 non-responders (27%). Thus, 37 of 420 patients
      (8.8%) were regarded as treatment failures. Of these 37 patients, transformation
      into diffuse large B cell lymphoma occurred in nine patients. Among the non
      responders and relapsed patients, 17 patients were subjected to a 'watch and
      wait' strategy while 90 patients underwent second-line treatments including
      radiotherapy (n=49), chemotherapy (n=26), surgical resection (n=6),
      chemoradiotherapy (n=5), antibiotic treatment (n=2), rituximab monotherapy (n=1)
      or endoscopic resection (n=1). Probabilities of freedom from treatment failure,
      overall survival and event-free survival after 10 years were 90%, 95% and 86%,
      respectively. Cox multivariate analysis revealed endoscopic non-superficial type
      to be an independent prognostic factor for adverse freedom from treatment
      failure, overall survival and event-free survival. CONCLUSIONS: The excellent
      long-term outcome of gastric MALT lymphoma after H pylori eradication was
      confirmed by this large-scale follow-up study.

PMID- 21890817
TI  - Zap1 control of cell-cell signaling in Candida albicans biofilms.
AB  - Biofilms of Candida albicans include both yeast cells and hyphae. Prior studies
      indicated that a zap1Delta/Delta mutant, defective in zinc regulator Zap1, has
      increased accumulation of yeast cells in biofilms. This altered yeast-hypha
      balance may arise from internal regulatory alterations or from an effect on the
      production of diffusible quorum-sensing (QS) molecules. Here, we develop
      biosensor reporter strains that express yeast-specific YWP1-RFP or hypha-specific
      HWP1-RFP, along with a constitutive TDH3-GFP normalization standard. Seeding
      these biosensor strains into biofilms allows a biological activity assay of the
      surrounding biofilm milieu. A zap1Delta/Delta biofilm induces the yeast-specific
      YWP1-RFP reporter in a wild-type biosensor strain, as determined by both
      quantitative reverse transcription-PCR (qRT-PCR) gene expression measurements and
      confocal microscopy. Remediation of the zap1Delta/Delta zinc uptake defect
      through zinc transporter gene ZRT2 overexpression reverses induction of the yeast
      specific YWP1-RFP reporter. Gas chromatography-mass spectrometry (GC-MS)
      measurements of known organic QS molecules show that the zap1Delta/Delta mutant
      accumulates significantly less farnesol than wild-type or complemented strains
      and that ZRT2 overexpression does not affect farnesol accumulation. Farnesol is a
      well-characterized inhibitor of hypha formation; hence, a reduction in farnesol
      levels in zap1Delta/Delta biofilms is unexpected. Our findings argue that a Zap1-
      and zinc-dependent signal affects the yeast-hypha balance and that it is
      operative in the low-farnesol environment of the zap1Delta/Delta biofilm. In
      addition, our results indicate that Zap1 is a positive regulator of farnesol
      accumulation.

PMID- 21890818
TI  - RAS/cyclic AMP and transcription factor Msn2 regulate mating and mating-type
      switching in the yeast Kluyveromyces lactis.
AB  - In response to harsh environmental conditions, ascomycetes produce stress
      resistant spores to promote survival. As sporulation requires a diploid DNA
      content, species with a haploid lifestyle, such as Kluyveromyces lactis, first
      induce mating in response to stress. In K. lactis, mating and mating-type
      switching are induced by the DNA-binding protein Mts1. Mts1 expression is known
      to be upregulated by nutrient limitation, but the mechanism is unknown. We show
      that a ras2 mutation results in a hyperswitching phenotype. In contrast, strains
      lacking the phosphodiesterase Pde2 had lower switching rates compared to that of
      the wild type (WT). As Ras2 promotes cyclic AMP (cAMP) production and Pde2
      degrades cAMP, these data suggest that low cAMP levels induce switching. Because
      the MTS1 regulatory region contains several Msn2 binding sites and Msn2 is a
      transcription factor that is activated by low cAMP levels, we investigated if
      Msn2 regulates MTS1 transcription. Consistently with this idea, an msn2 mutant
      strain displayed lower switching rates than the WT strain. The transcription of
      MTS1 is highly induced in the ras2 mutant strain. In contrast, an msn2 ras2
      double mutant strain displays WT levels of the MTS1 transcript, showing that Msn2
      is a critical inducer of MTS1 transcription. Strains lacking Msn2 and Pde2 also
      exhibit mating defects that can be complemented by the ectopic expression of
      Mts1. Finally, we show that MTS1 is subjected to negative autoregulation,
      presumably adding robustness to the mating and switching responses. We suggest a
      model in which Ras2/cAMP/Msn2 mediates the stress-induced mating and mating-type
      switching responses in K. lactis.

PMID- 21890819
TI  - Protein phosphatase Pph3 and its regulatory subunit Psy2 regulate Rad53
      dephosphorylation and cell morphogenesis during recovery from DNA damage in
      Candida albicans.
AB  - The ability of the pathogenic fungus Candida albicans to switch cellular
      morphologies is important for infection and virulence. Recent studies have
      revealed that C. albicans yeast cells can switch to filamentous growth under
      genotoxic stress in a manner dependent on the DNA replication/damage checkpoint.
      Here, we have investigated the functions of Pph3 (orf19.4378) and Psy2
      (orf19.3685), whose orthologues in Saccharomyces cerevisiae mediate the
      dephosphorylation of the DNA damage checkpoint kinase Rad53 and the histone
      variant H2AX during recovery from DNA damage. Deleting PPH3 or PSY2 causes
      hypersensitivity to DNA-damaging agents, including cisplatin, methylmethane
      sulfonate (MMS), and UV light. In addition, pph3Delta and psy2Delta cells exhibit
      strong filamentous growth under genotoxic stress. Flow cytometry analysis shows
      that the mutant cells have lost the ability to adapt to genotoxic stress and
      remain arrested even after the stress is withdrawn. Furthermore, we show that
      Pph3 and Psy2 are required for the dephosphorylation of Rad53, but not H2AX,
      during DNA damage recovery. Taken together, these results show that C. albicans
      Pph3 and Psy2 have important roles in mediating genotoxin-induced filamentous
      growth and regulating Rad53 dephosphorylation.

PMID- 21890820
TI  - Expression of biomass-degrading enzymes is a major event during conidium
      development in Trichoderma reesei.
AB  - The conidium plays a critical role in the life cycle of many filamentous fungi,
      being the primary means for survival under unfavorable conditions. To investigate
      the transcriptional changes taking place during the transition from growing
      hyphae to conidia in Trichoderma reesei, microarray experiments were performed. A
      total of 900 distinct genes were classified as differentially expressed, relative
      to their expression at time zero of conidiation, at least at one of the time
      points analyzed. The main functional categories (FunCat) overrepresented among
      the upregulated genes were those involving solute transport, metabolism,
      transcriptional regulation, secondary metabolite synthesis, lipases, proteases,
      and, particularly, cellulases and hemicellulases. Categories overrepresented
      among the downregulated genes were especially those associated with ribosomal and
      mitochondrial functions. The upregulation of cellulase and hemicellulase genes
      was dependent on the function of the positive transcriptional regulator XYR1, but
      XYR1 exerted no influence on conidiation itself. At least 20% of the
      significantly regulated genes were nonrandomly distributed within the T. reesei
      genome, suggesting an epigenetic component in the regulation of conidiation. The
      significant upregulation of cellulases and hemicellulases during this process,
      and thus cellulase and hemicellulase content in the spores of T. reesei,
      contributes to the hypothesis that the ability to hydrolyze plant biomass is a
      major trait of this fungus enabling it to break dormancy and reinitiate
      vegetative growth after a period of facing unfavorable conditions.

PMID- 21890821
TI  - Evolutionary dynamics of Candida albicans during in vitro evolution.
AB  - While mechanisms of resistance to major antifungal agents have been characterized
      in Candida albicans, little is known about the evolutionary trajectories during
      the emergence of drug resistance. Here, we examined the evolutionary dynamics of
      C. albicans that evolved in vitro in the presence or absence of fluconazole using
      the visualizing evolution in real-time (VERT) method, a novel experimental
      approach that facilitates the systematic isolation of adaptive mutants that arise
      in the population. We found an increase in the frequency of adaptive events in
      the presence of fluconazole compared to the no-drug controls. Analysis of the
      evolutionary dynamics revealed that mutations that led to increased drug
      resistance appeared frequently and that mutants with increased levels of
      resistance arose in independent lineages. Interestingly, most adaptive mutants
      with increased fitness in the presence of the drug did not exhibit a significant
      fitness decrease in the absence of the drug, supporting the idea that rapid
      resistance can arise from mutations in strains maintained in the population prior
      to exposure to the drug.

PMID- 21890824
TI  - Risk factors for childhood mental health symptoms: national longitudinal study of
      Australian children.
AB  - OBJECTIVE: To determine predictors of child externalizing (behavioral) and
      internalizing (emotional) symptoms in a national population sample. METHODS: Data
      were collected in 3 biennial waves (2004, 2006, and 2008) from 2 cohorts in the
      Longitudinal Study of Australian Children, initially including 5107 children 0 to
      1 year of age and 4983 children 4 to 5 years of age. The primary outcomes were
      child externalizing and internalizing symptoms. Relationships between potential
      risk factors and child mental health outcomes were described by using linear
      regression. RESULTS: In unadjusted analyses, children's mental health symptoms
      were predicted by a large number of risk factors. In multivariate models, early
      childhood factors (birth through 5 years) explained 30% and 18% of variations in
      externalizing and internalizing symptoms, respectively, at 4 to 5 years of age.
      Middle childhood (5-9 years of age) factors explained 20% and 23% of variations
      in externalizing and internalizing symptoms, respectively, at 8 to 9 years of
      age. Harsh discipline was a strong consistent predictor of externalizing symptoms
      in both age groups, whereas poorer child physical health, maternal emotional
      distress, harsh discipline, and overinvolved/protective parenting (younger cohort
      only) predicted internalizing symptoms consistently. CONCLUSIONS: National data
      on predictors of child mental health symptoms highlighted a small number of
      significant risk factors, situated in the family context and present from a very
      young age. This knowledge is informing population-level, randomized, prevention
      trials of family support programs.

PMID- 21890823
TI  - Age-specific differences in outcomes after out-of-hospital cardiac arrests.
AB  - OBJECTIVE: We assessed out-of-hospital cardiac arrests (OHCAs) for various
      pediatric age groups. METHODS: This prospective, population-based, observational
      study included all emergency medical service-treated OHCAs in Osaka, Japan,
      between 1999 and 2006 (excluding 2004). Patients were grouped as adults (>17
      years), infants (<1 year), younger children (1-4 years), older children (5-12
      years), and adolescents (13-17 years). The primary outcome measure was 1-month
      survival with favorable neurologic outcome. RESULTS: Of 950 pediatric OHCAs,
      resuscitations were attempted for 875 patients (92%; 347 infants, 203 younger
      children, 135 older children, and 190 adolescents). The overall incidence of
      nontraumatic pediatric OHCAs was 7.3 cases per 100 000 person-years, compared
      with 64.7 cases per 100 000 person-years for adults and 65.5 cases per 100 000
      person-years for infants. Most infant OHCAs occurred in homes (93%) and were not
      witnessed (90%). Adolescent OHCAs often occurred outside the home (45%), were
      witnessed by bystanders (37%), and had shockable rhythms (18%). One-month
      survival was more common after nontraumatic pediatric OHCAs than adult OHCAs (8%
      [56 of 740 patients] vs 5% [1677 of 33 091 patients]; adjusted odds ratio: 2.26
      [95% confidence interval: 1.63-3.13]). One-month survival with favorable
      neurologic outcome was more common among children than adults (3% [21 of 740
      patients] vs 2% [648 of 33 091 patients]; adjusted odds ratio: 2.46 [95%
      confidence interval: 1.45-4.18]). Rates of 1-month survival with favorable
      neurologic outcome were 1% for infants, 2% for younger children, 2% for older
      children, and 11% for adolescents. CONCLUSION: Survival and favorable neurologic
      outcome at 1 month were more common after pediatric OHCAs than adult OHCAs.

PMID- 21890825
TI  - A brief sleep intervention improves outcomes in the school entry year: a
      randomized controlled trial.
AB  - OBJECTIVE: To determine the feasibility of screening for child sleep problems and
      the efficacy of a behavioral sleep intervention in improving child and parent
      outcomes in the first year of schooling. METHODS: A randomized controlled trial
      was nested in a population survey performed at 22 elementary schools in
      Melbourne, Australia. Intervention involved 2 to 3 consultations that covered
      behavioral sleep strategies for children whose screening results were positive
      for a moderate/severe sleep problem. Outcomes were parent-reported child sleep
      problem (primary outcome), sleep habits, psychosocial health-related quality of
      life, behavior, and parent mental health (all at 3, 6, and 12 months) and
      blinded, face-to-face learning assessment (at 6 months). RESULTS: The screening
      survey was completed by 1512 parents; 161 (10.8%) reported a moderate/severe
      child sleep problem, and 108 of 136 (79.2% of those eligible) entered the trial.
      Sleep problems tended to resolve more rapidly in intervention children. Sleep
      problems affected 33% of 54 intervention children versus 43% of 54 control
      children at 3 months (P = .3), 25.5% vs 46.8% at 6 months (P = .03), and 32% vs
      33% at 12 months (P = .8). Sustained sleep-habit improvements were evident at 3,
      6, and 12 months (effect sizes: 0.33 [P = .03]; 0.51 [P = .003]; and 0.40 [P =
      .02]; respectively), and there were initial marked improvements in psychosocial
      scores that diminished over time (effect sizes: 0.47 [P = .02]; 0.41 [P = .09];
      and 0.26 [P = .3]; respectively). Better prosocial behavior was evident at 12
      months (effect size: 0.35; P = .03), and learning and parent outcomes were
      similar between groups. CONCLUSIONS: School-based screening for sleep problems
      followed by a targeted, brief behavioral sleep intervention is feasible and has
      benefits relevant to school transition.

PMID- 21890822
TI  - A NOTCH3-mediated squamous cell differentiation program limits expansion of EMT
      competent cells that express the ZEB transcription factors.
AB  - Zinc finger E-box-binding (ZEB) proteins ZEB1 and ZEB2 are transcription factors
      essential in TGF-beta-mediated senescence, epithelial-to-mesenchymal transition
      (EMT), and cancer stem cell functions. ZEBs are negatively regulated by members
      of the miR-200 microRNA family, but precisely how tumor cells expressing ZEBs
      emerge during invasive growth remains unknown. Here, we report that NOTCH3
      mediated signaling prevents expansion of a unique subset of ZEB-expressing cells.
      ZEB expression was associated with the lack of cellular capability of undergoing
      NOTCH3-mediated squamous differentiation in human esophageal cells. Genetic
      inhibition of the Notch-mediated transcriptional activity by dominant-negative
      Mastermind-like 1 (DNMAML1) prevented squamous differentiation and induction of
      Notch target genes including NOTCH3. Moreover, DNMAML1-enriched EMT-competent
      cells exhibited robust upregulation of ZEBs, downregulation of the miR-200
      family, and enhanced anchorage-independent growth and tumor formation in nude
      mice. RNA interference experiments suggested the involvement of ZEBs in anchorage
      independent colony formation, invasion, and TGF-beta-mediated EMT. Invasive
      growth and impaired squamous differentiation were recapitulated upon Notch
      inhibition by DNMAML1 in organotypic three-dimensional culture, a form of human
      tissue engineering. Together, our findings indicate that NOTCH3 is a key factor
      limiting the expansion of ZEB-expressing cells, providing novel mechanistic
      insights into the role of Notch signaling in the cell fate regulation and disease
      progression of esophageal squamous cancers.

PMID- 21890826
TI  - School absenteeism among children living with smokers.
AB  - OBJECTIVE: Involuntary tobacco smoke exposure causes substantial morbidity in
      children. We hypothesized that children exposed to tobacco smoke in the home
      would have increased school absenteeism with associated costs due to lost
      caregiver wages/time. METHODS: We analyzed data on health and absenteeism among
      schoolchildren aged 6 to 11 years identified in the 2005 National Health
      Interview Survey (NHIS). We used multivariate models to assess the relationships
      between adult-reported household smoking and child health and school absenteeism.
      Analyses were adjusted for children's and parents' demographic and socioeconomic
      characteristics. The value of lost caregiver time was estimated by using self
      reported employment and earnings data in the NHIS and publicly available time-use
      data. RESULTS: Children living with 1 or >= 2 adults who smoked in the home had
      1.06 (95% confidence interval [CI]: 0.54-1.55) and 1.54 (95% CI: 0.95-2.12) more
      days absent from school per year, respectively, than children living with 0
      smokers in the home. Living with >= 2 adults who smoked in the home was
      associated with increased reports of having >= 3 ear infections in the previous
      12 months (adjusted odds ratio [aOR]: 2.65 [95% CI: 1.36-5.16]) and having a
      chest cold in the 2 weeks before interview (aOR: 1.77 [95% CI: 1.03-3.03]) but
      not with having vomiting/diarrhea in the previous 2 weeks (aOR: 0.93 [95% CI:
      0.45-1.89]). Caregivers' time tending children absent from school was valued at
      $227 million per year. CONCLUSIONS: Tobacco smoke exposure has significant
      consequences for children and families above and beyond child morbidity,
      including academic disadvantage and financial burden.

PMID- 21890827
TI  - Development of a novel curriculum to enhance the autonomy and motivation of
      residents.

PMID- 21890828
TI  - Effect on behavior problems of teen online problem-solving for adolescent
      traumatic brain injury.
AB  - PURPOSE: To report the results of a randomized clinical trial of teen online
      problem-solving (TOPS) meant to improve behavioral outcomes of adolescents with
      traumatic brain injury (TBI). METHODS: A randomized clinical trial was conducted
      to compare the efficacy of TOPS with access to Internet resources in teenagers
      with TBI in improving parent and self-reported behavior problems and parent-teen
      conflicts. Participants included 41 adolescents aged 11 to 18 years (range: 11.47
      17.90 years) who had sustained a moderate-to-severe TBI between 3 and 19 months
      earlier. Teens in the TOPS group received 10 to 14 online sessions that provided
      training in problem-solving, communication skills, and self-regulation. Outcomes
      were assessed before treatment and at a follow-up assessment an average of 8
      months later. Groups were compared on follow-up scores after we controlled for
      pretreatment levels. Injury severity and socioeconomic status were examined as
      potential moderators of treatment efficacy. RESULTS: Forty-one participants
      provided consent and completed baseline assessments, and follow-up assessments
      were completed for 35 participants (16 TOPS, 19 Internet resource comparison).
      The TOPS group reported significantly less parent-teen conflict at follow-up than
      did the Internet-resource-comparison group. Improvements in teen behavior after
      TOPS were moderated by injury severity; there were greater improvements in the
      teens' internalizing symptoms after TOPS among adolescents with severe TBI.
      Family socioeconomic status also moderated the efficacy of TOPS in improving
      behavior problems reported by both parents and teens, although the nature of the
      moderation effects varied. CONCLUSION: Our findings suggest that TOPS contributes
      to improvements in parent-teen conflict generally and parent and self-reported
      teen behavior problems for certain subsets of participants.

PMID- 21890829
TI  - Recurrence and outcomes of Stevens-Johnson syndrome and toxic epidermal
      necrolysis in children.
AB  - OBJECTIVES: To report clinical course, etiology, management, and long-term
      outcomes of children suffering from Stevens-Johnson syndrome (SJS) or toxic
      epidermal necrolysis (TEN). METHODS: We conducted a study of all pediatric
      patients with SJS or TEN admitted between 2000 and 2007 to the Hospital for Sick
      Children and Children's Hospital Boston, and particular attention was paid to
      clinical manifestations, etiology, mortality, and long-term outcomes. RESULTS: We
      identified 55 cases of SJS (n = 47), TEN (n = 5), or SJS/TEN overlap syndrome (n
      = 3). Drugs were identified as the most likely etiologic agent in 29 children
      (53%); antiepileptic drugs were the most common agents (n = 16), followed by
      sulfonamide antibiotics (n = 7) and chemotherapy drugs (n = 2). Acute Mycoplasma
      pneumoniae infection was confirmed in 12 children (22%), and herpes simplex virus
      was confirmed in 5 children (9%). Treatment regimens differed significantly
      between participating sites and included systemic antimicrobial agents (67%),
      systemic corticosteroids (40%), and antiviral drugs (31%). Intravenous
      immunoglobulin was administered to 21 children (38%), of whom 8 received
      concomitant systemic corticosteroids. Ten children (18%) had recurrence of SJS up
      to 7 years after the index episode, and 3 experienced multiple recurrences.
      Twenty-six children (47%) suffered long-term sequelae that mostly involved the
      skin and eyes. CONCLUSIONS: Mortality rate in children was lower than that
      reported in adults, but half of affected children suffered long-term
      complications. The recurrence rate of SJS was high (1 in 5), which suggests
      vulnerability and potential genetic predisposition. In the absence of
      standardized management guidelines for these conditions, treatment regimens
      differed significantly between participating institutions.

PMID- 21890830
TI  - Statistical uncertainty of mortality rates and rankings for children's hospitals.
AB  - OBJECTIVES: Hospitals are being required to report publically their adjusted
      mortality rates, which are then being used to rank hospitals. Our objectives were
      to assess the statistical reliability of the determination of a hospital's
      adjusted mortality rate, of comparisons of that rate with the rates of other
      hospitals, and of the use of those rates to rank the hospitals. METHODS: A cross
      sectional study of 473 383 patients discharged from 42 US children's hospitals in
      2008 was performed. Hospital-specific observed/expected (O/E) mortality rate
      ratios and corresponding hospital rankings, with 95% confidence intervals (CIs),
      were examined. RESULTS: Hospitals' O/E mortality rate ratios exhibited wide 95%
      CIs, and no hospital was clearly distinguishable from the other hospitals'
      aggregated mean mortality performance. Only 2 hospitals' mortality performance
      fell outside the comparator hospitals' 95% CI. Those hospitals' 95% CIs
      overlapped with the overall comparator set's 95% CI, which suggests that there
      were no statistically significant hospital outliers. Fourteen (33.3%) of the 42
      hospitals had O/E ratios that were not statistically different from being in the
      95% CI of the top 10% of hospitals. Hospital-specific mortality rate rankings
      displayed even broader 95% CIs; the typical hospital had a 95% CI range that
      spanned 22 rank-order positions. CONCLUSION: Children's hospital-specific
      measures of adjusted mortality rate ratios and rankings have substantial amounts
      of statistical imprecision, which limits the usefulness of such measures for
      comparisons of quality of care.

PMID- 21890831
TI  - Race, ancestry, and development of food-allergen sensitization in early
      childhood.
AB  - OBJECTIVE: We examined whether the risk of food-allergen sensitization varied
      according to self-identified race or genetic ancestry. METHODS: We studied 1104
      children (mean age: 2.7 years) from an urban multiethnic birth cohort. Food
      sensitization was defined as specific immunoglobulin E (sIgE) levels of >= 0.35
      kilo-units of allergen (kUA)/L for any of 8 common food allergens. Multivariate
      logistic regression analyses were used to evaluate the associations of self
      identified race and genetic ancestry with food sensitization. Analyses also
      examined associations with numbers of food sensitizations (0, 1 or 2, and >= 3
      foods) and with logarithmically transformed allergen sIgE levels. RESULTS: In
      this predominantly minority cohort (60.9% black and 22.5% Hispanic), 35.5% of
      subjects exhibited food sensitizations. In multivariate models, both self
      reported black race (odds ratio [OR]: 2.34 [95% confidence interval [CI]: 1.24
      4.44]) and African ancestry (in 10% increments; OR: 1.07 [95% CI: 1.02-1.14])
      were associated with food sensitization. Self-reported black race (OR: 3.76 [95%
      CI: 1.09-12.97]) and African ancestry (OR: 1.19 [95% CI: 1.07-1.32]) were
      associated with a high number (>= 3) of food sensitizations. African ancestry was
      associated with increased odds of peanut sIgE levels of >= 5 kUA/L (OR: 1.25 [95%
      CI: 1.01-1.52]). Similar ancestry associations were seen for egg sIgE levels of
      >= 2 kUA/L (OR: 1.13 [95% CI: 1.01-1.27]) and milk sIgE levels of >= 5 kUA/L (OR:
      1.24 [95% CI: 0.94-1.63]), although findings were not significant for milk.
      CONCLUSIONS: Black children were more likely to be sensitized to food allergens
      and were sensitized to more foods. African ancestry was associated with peanut
      sensitization.

PMID- 21890832
TI  - Nurse practitioners and physician assistants employed by general and subspecialty
      pediatricians.
AB  - OBJECTIVE: There is little nationally representative information describing the
      current manner in which nurse practitioners (NPs) and physician assistants (PAs)
      work in pediatric practices and their professional activities. To understand
      better the current NP and PA workforce in pediatric primary and subspecialty
      care, we conducted a national survey of pediatricians. METHODS: A survey study of
      a random national sample of 498 pediatric generalists and 1696 subspecialists in
      the United States was performed by using a structured questionnaire administered
      by mail. The survey focused on practice settings, employment, and scope of work
      of NPs and PAs. RESULTS: Response rates were 72% for generalists and 77% for
      subspecialists. More than one-half (55%) of generalists reported that they do not
      currently work with NPs or PAs, compared with only one-third of subspecialists
      who do not. Many generalists and subspecialists intend to increase the number of
      NPs and PAs in their practices in the next 5 years. More generalist and
      subspecialty practices work with NPs than with PAs. There was great variability
      between generalists and subspecialists and among different subspecialties in the
      proportions that worked with NPs and PAs. The scope of work of NPs and PAs also
      varied between generalists and subspecialists. CONCLUSIONS: Planned increases in
      the number of NPs hired and expansion of their scope of work might put
      subspecialists and general pediatricians in competition with regard to
      recruitment and hiring of a limited pool of new pediatric NPs. Similar issues
      might arise with PAs.

PMID- 21890833
TI  - Clinical presentation and treatment of transfusion-associated babesiosis in
      premature infants.
AB  - We review here 7 cases of neonatal transfusion-associated babesiosis at a NICU in
      the northeast United States. Transfusion from 2 infected units of blood resulted
      in the 7 cases described. The clinical presentation was highly variable in this
      cohort; the extremely low birth weight neonates were the most severely affected.
      Antibiotic therapy was effective in neonates with mild and asymptomatic
      infection; however, double-volume exchange blood transfusion with prolonged
      multidrug treatment was required for the 2 most severe cases. The risk of Babesia
      microti infection is not eliminated through current blood-bank practices.
      Neonatologists in endemic areas should have a high index of suspicion for
      babesiosis in premature infants exposed to blood transfusions.

PMID- 21890834
TI  - Recommendations for prevention and control of influenza in children, 2011-2012.
AB  - The purpose of this statement is to update recommendations for routine use of
      trivalent seasonal influenza vaccine and antiviral medications for the prevention
      and treatment of influenza in children. The key points for the upcoming 2011-2012
      season are that (1) the influenza vaccine composition for the 2011-2012 season is
      unchanged from the 2010-2011 season, (2) annual universal influenza immunization
      is indicated, (3) a simplified dosing algorithm for administration of influenza
      vaccine to children 6 months through 8 years of age has been created, (4) most
      children presumed to have egg allergy can safely receive influenza vaccine in the
      office without need for an allergy consultation, and (5) an intradermal trivalent
      inactivated influenza vaccine has been licensed for the 2011-2012 season for use
      in people 18 through 64 years of age. Pediatricians, nurses, and all health care
      personnel have leadership roles in the prevention of influenza through vaccine
      use and public education. In addition, pediatricians should promptly identify
      influenza infections to enable rapid treatment, when indicated, to reduce
      childhood morbidity and mortality.

PMID- 21890835
TI  - Genetic and management approaches to boost UK wheat yields by ameliorating water
      deficits.
AB  - Faced with the challenge of increasing global food production, there is the need
      to exploit all approaches to increasing crop yields. A major obstacle to boosting
      yields of wheat (an important staple in many parts of the world) is the
      availability and efficient use of water, since there is increasing stress on
      water resources used for agriculture globally, and also in parts of the UK.
      Improved soil and crop management and the development of new genotypes may
      increase wheat yields when water is limiting. Technical and scientific issues
      concerning management options such as irrigation and the use of growth-promoting
      rhizobacteria are explored, since these may allow the more efficient use of
      irrigation. Fundamental understanding of how crops sense and respond to multiple
      abiotic stresses can help improve the effective use of irrigation water.
      Experiments are needed to test the hypothesis that modifying wheat root system
      architecture (by increasing root proliferation deep in the soil profile) will
      allow greater soil water extraction thereby benefiting productivity and yield
      stability. Furthermore, better knowledge of plant and soil interactions and how
      below-ground and above-ground processes communicate within the plant can help
      identify traits and ultimately genes (or alleles) that will define genotypes that
      yield better under dry conditions. Developing new genotypes will take time and,
      therefore, these challenges need to be addressed now.

PMID- 21890836
TI  - Reliability of self-rated health in US adults.
AB  - General self-rated health (SRH) is widely used to study trends and inequalities
      in population health. Recently, there has been an increased interest in
      understanding the measurement properties of SRH. This study evaluated for the
      first time the test-retest reliability of SRH among US adults. Analyses were
      based on a nationally representative sample of 9,235 adults interviewed in the
      2005-2008 National Health and Nutrition Examination Survey (NHANES). Respondents
      reported SRH on 2 occasions (about 1 month apart). Kappa statistics, polyserial
      correlations, and agreement tabulations were used to assess reliability across
      population subgroups; regression models tested the association of
      sociodemographic factors and the stability of the rating. Nearly 40% of
      respondents changed their health rating between interviews, indicating moderate
      test-retest reliability of SRH. Reliability differed significantly by
      sociodemographic characteristics: Racial/ethnic minorities and adults with less
      education had lower reliability of SRH judgments. Health events between
      interviews did not influence consistency, but conditional on a rating change,
      they increased the odds of downgrading one's health. The results suggest that 1)
      there is a substantial amount of error in individuals' self-assessment of health
      and 2) reliability is worse for disadvantaged sociodemographic groups,
      potentially biasing estimates of health inequalities among US adults.

PMID- 21890838
TI  - Utility of post-urinary tract infection imaging in patients with normal prenatal
      renal ultrasound.
AB  - The American Academy of Pediatrics recommends renal ultrasound (RUS) and voiding
      cystourethrography (VCUG) for all infants after a first urinary tract infection
      (UTI). However, many congenital renal anomalies are identified by a prenatal US.
      At the present time, there are no data regarding the yield of post-UTI imaging
      among infants who have a documented normal prenatal US. We retrospectively
      reviewed the charts of all patients <1 year of age with a first UTI who had
      normal kidneys noted on prenatal US to determine the frequency of abnormal
      findings. Abnormal RUS and VCUG results were noted in 5.1% (24 of 471) and 20.4%
      (75 of 368) of infants, respectively. While the abnormal US rate is significantly
      less than what has been previously reported, the frequency of abnormal VCUGs is
      similar. These results suggest that a post-UTI RUS may not be needed if the
      prenatal US was normal. However, a VCUG continues to be indicated.

PMID- 21890837
TI  - Green tea polyphenol epigallocatechin gallate activates TRPA1 in an intestinal
      enteroendocrine cell line, STC-1.
AB  - A characteristic astringent taste is elicited by polyphenols. Among the
      polyphenols, catechins and their polymers are the most abundant polyphenols in
      wine and tea. A typical green tea polyphenol is epigallocatechin gallate (EGCG).
      Currently, the mechanism underlying the sensation of astringent taste is not well
      understood. We observed by calcium imaging that the mouse intestinal endocrine
      cell line STC-1 responds to the astringent compound, EGCG. Among major catechins
      of green tea, EGCG was most effective at eliciting a response in this cell line.
      This cellular response was not observed in HEK293T or 3T3 cells. Further analyses
      demonstrated that the 67-kDa laminin receptor, a known EGCG receptor, is not
      directly involved. The Ca(2+) response to EGCG in STC-1 cells was decreased by
      inhibitors of the transient receptor potential A1 (TRPA1) channel. HEK293T cells
      transfected with the mouse TRPA1 (mTRPA1) cDNA showed a Ca(2+) response upon
      application of EGCG, and their response properties were similar to those observed
      in STC-1 cells. These results indicate that an astringent compound, EGCG,
      activates the mTRPA1 in intestinal STC-1 cells. TRPA1 might play an important
      role in the astringency taste on the tongue.

PMID- 21890839
TI  - The impact of CHIP coverage on children with asthma in Alabama.
AB  - This study evaluates the impact of coverage in ALL Kids, the Alabama Child Health
      Insurance Program (CHIP), by examining asthma-related utilization and outcomes
      among children continuously enrolled for 3 years (N = 1954)with persistent asthma
      at enrollment. Outcomes and costs were compared for the first, second, and third
      years of enrollment using repeated measures analysis of variance and controlling
      for age, gender, and year fixed-effects. Compared with subsequent years, first
      year enrollment utilization was higher for asthma-related hospitalizations (6% vs
      2% vs 2%; P < .0001) and emergency visits (10% vs 3% vs 2%; P < .0001). Also
      decreasing were asthma-related outpatient visits (1.46 vs 1.12 vs 0.94; P <
      .0001), quick-relief prescriptions (2.6 vs 2.2 vs 2.1; P < .0001), and long-term
      control prescriptions (5.8 vs 5.2 vs 4.4; P < .0001). As a result, significant
      declines in the mean costs per child were observed. Ongoing ALL Kids coverage is
      associated with improved disease-management and lower costs for persistent
      asthma.

PMID- 21890840
TI  - Genetic signature of reproductive manipulation in the phylogeography of the bat
      fly, Trichobius major.
AB  - The bat fly (Trichobius major) is a blood-feeding ectoparasite of the cave myotis
      (Myotis velifer). A recent mitochondrial DNA (mtDNA) study examining population
      structure of T. major in the South Central United States detected a single
      haplotype from all individuals examined (N = 48 from 12 different caves),
      representing one of only a few known examples of such widespread mtDNA
      uniformity. We examined nuclear genetic diversity using amplified fragment length
      polymorphism and detected high levels of nuclear genetic diversity in all
      populations sampled. Amplified fragment length polymorphism analyses indicated
      significant levels of gene flow among caves >700 km apart, suggesting the absence
      of mtDNA diversity in T. major is the result of a selective sweep, not a
      demographic event (i.e., a recent bottleneck). One mechanism by which mtDNA
      sweeps occur in arthropods is through bacterial parasites that manipulate host
      reproduction and mtDNA inheritance. We used PCR to test for the presence of all
      known reproductive parasites and detected a widespread infection (91.33%
      infection rate) of T. major with a novel Arsenophonus bacterium, as well as the
      infection of 2 individuals (1.16% infection rate) with a novel strain of
      Rickettsia. We discuss the implications for T. major phylogeography and the
      necessity of a bigenomic approach in arthropod population genetics.

PMID- 21890842
TI  - Quality of diabetes care in public primary care clinics in Hong Kong.
AB  - BACKGROUND: Little is known about the quality of care for patients with Type 2
      diabetes in primary care setting in Hong Kong. OBJECTIVES: To investigate the
      quality of care for patients with Type 2 diabetes in Hong Kong primary care
      setting and potential disparities by patient characteristics and clinics.
      METHODS: Cross-sectional study in three general outpatient clinics (GOPCs; public
      primary care clinics) in Hong Kong involving 1970 patients. Main outcome measures
      were achievement rates of seven process measures and three intermediate outcome
      targets and adjusted odds ratios of age, sex, socio-economic status and clinic on
      the quality measures. RESULTS: The achievement rates for the recording of HbA1c,
      blood pressure (BP), cholesterol, body mass index, smoking status, nephropathy
      screening and retinopathy screening in the previous 12 months were 92.8%, 99.9%,
      91.0%, 47.9%, 91.3%, 69.0% and 38.0%, respectively. A total of 58.0%, 38.2% and
      36.4% of patients achieved the glycaemic, BP and cholesterol targets,
      respectively. Older patients were less likely to have records of process measures
      and more likely to achieve the HbA1c target. Women were less likely to have
      smoking status recorded and to achieve the HbA1c target. Patients of lower socio
      economic status were less likely to have records of process measures and to
      achieve the BP target. Family medicine training practices had better achievements
      of the quality measures. CONCLUSIONS: There is scope for improvement in the
      quality of diabetes care in the GOPCs. Variations in the quality of care were
      observed. Family medicine training may enhance the health care quality.

PMID- 21890841
TI  - Investigation of thyroid dysfunction is more likely in patients with high
      psychological morbidity.
AB  - BACKGROUND: Mild or subclinical hypothyroidism [raised thyroid-stimulating
      hormone (TSH) but normal free thyroxine (T4)] affects 5-10% of adults. Symptoms
      are non-specific and TSH levels are needed for diagnosis. OBJECTIVES: We explore
      the relationship between thyroid function and psychological distress and
      investigate the usefulness of an expert-designed Thyroid Symptom Questionnaire
      (TSQ) in identifying hypothyroidism. METHODS: DEPTH (DEPression and THyroid) is a
      cross-sectional study of 325 patients recruited from general practices in
      Bristol, for whom thyroid function tests were requested by the GP. Subjects
      completed the TSQ, General Health Questionnaire (GHQ-12) and Patient Health
      Questionnaire (PHQ) and had blood tests for TSH and free T4. RESULTS: The mean
      age was 45.7 years; 252 subjects (78%) were female; median TSH was 1.6.
      Psychological morbidity in this population is high: 54.2% have a GHQ-12 score >3,
      indicating psychological distress. We found no relationship between TSH and
      psychological distress [adjusted odds ratio 1.02 (95% confidence interval 0.91
      1.13), P = 0.78]. The prevalence of hypothyroidism was 6.2% (95% confidence
      interval 3.8-9.5%). We found no evidence of an unadjusted association between TSQ
      score and subclinical hypothyroidism [adjusted odds ratio of 1.09 (95% confidence
      interval 0.95-1.24), P = 0.23]. CONCLUSIONS: Those referred for thyroid function
      tests, although no more likely than others to have hypothyroidism, have high
      rates of psychological distress. When mild (subclinical) hypothyroidism is
      detected in patients with psychological distress, it is important that GPs are
      aware that this is likely to be coincidental rather than causal and offer
      appropriate treatment.

PMID- 21890843
TI  - Changes in social-cognitive variables are associated with stage transitions in
      physical activity.
AB  - When it comes to the adoption or maintenance of physical activity, individuals
      can be placed along a continuum or into stages of change. The Health Action
      Process Approach proposes three such stages: non-intentional, intentional and
      actional. Intraindividual differences are reflected by stage transitions: either
      progression or regression. The present study examines social-cognitive factors of
      stage transitions: outcome expectancies, self-efficacy and planning. In an online
      study on physical activity, 660 adults completed questionnaires at baseline and
      approximately 3 weeks later. Social-cognitive factors were converted into
      standardized residual change scores to account for changes in outcome
      expectancies, self-efficacy and planning within the observation period.
      Discriminant function analyses revealed stage-specific patterns: progression out
      of non-intentional stage was associated with self-efficacy increases. Out of
      intentional stage, regression was correlated with decreases in planning, whereas
      progression was linked to increases in self-efficacy and planning. Regression
      from action stage was associated with decreases in self-efficacy. Physical
      activity promotion should focus on improving self-efficacy for non-intending,
      intending and acting individuals, whereas planning interventions are recommended
      for intending individuals. Interventions may be more effective by considering
      specific mechanisms instead of providing generic interventions for all
      individuals at different stages.

PMID- 21890844
TI  - Results of the 'in control: no alcohol!' pilot study.
AB  - More than 50% of Dutch 12-year olds already started drinking. Since it is known
      that delaying the onset of alcohol use results in a lower risk of alcohol-related
      problems, the recently developed 'In control: No alcohol!' prevention program is
      targeted at elementary school children and their mothers. In this pilot study,
      the success of program implementation and impact of the program on quality of
      alcohol-specific communication, rules and monitoring were evaluated, using a
      randomized controlled design. A total of 108 children (11-12 years) and their
      mothers participated in the prevention program, while the control group consisted
      of 105 dyads. Families participating in the experimental condition showed an
      increase in frequency of alcohol-specific communication and 75% of the dyads
      reported that they took part in at least 3 of 5 magazines, suggesting
      implementation was successful. The program led to an increase in quality of
      communication but only for those dyads in which mothers' alcohol use was above
      average. The program led parents to set up a non-drinking contract with their
      children and to monitor their children more closely. Results are promising but
      need to be replicated in a larger longitudinal study.

PMID- 21890846
TI  - Rubrics 101: a primer for rubric development in dental education.
AB  - Identifying and implementing effective methods for assessing dental student
      performance are ongoing challenges for dental educators. Questions related to
      grading and assessment are common among faculty and students alike. Faculty
      members who are well-trained clinicians or scientists often have little formal
      training in education. In addition, assessment of performance brings with it an
      element of subjectivity. Questions about assessment and grading are most likely
      to arise when expectations are unclear or the rationale for the grade awarded is
      not articulated. The authors propose that one solution to assessment dilemmas can
      be found in the use of rubrics: scaled tools with levels of achievement and
      clearly defined criteria placed in a grid. Rubrics establish clear rules for
      evaluation and define the criteria for performance. Rubrics speak to both
      teaching and learning expectations and outcomes and can provide faculty members
      with a tool that can be useful in evaluating dental student performance. Rubrics
      can also provide students with clear expectations of performance, an opportunity
      to self-assess, and timely, detailed feedback. The purpose of this article is to
      define a rubric, apply the steps of rubric development as described in the
      educational literature to dental student assessment, present two examples of
      rubric implementation for assessing student progress toward competence, and
      recommend electronic resources for rubric development.

PMID- 21890847
TI  - Student-led courses to teach cone beam CT in the predoctoral dental curriculum.
AB  - Cone beam computed tomography (CBCT) provides a new method to evaluate the
      craniofacial region. The goal of our project was to introduce into the
      predoctoral dental curriculum a student-initiated, student-led introduction to
      CBCT and how to use it, with minimal expenditure of financial resources. A third
      year student worked with two faculty members to design a course in which a small
      number of third-year students would lead a small group of second-year students.
      The first approach involved each small group of second-year dental students
      discussing one clinical case in which the patient's CBCT record was included.
      Representatives of each of the ten small groups presented the patient and that
      patient's clinical problem (e.g., an impacted tooth) to the entire class as well
      as demonstrating the superiority and limitations of using CBCT in clinical
      dentistry. The second approach also used small-group meetings led by third-year
      dental students, but paired two second-year dental students as a team to present
      the patient's CBCT data in the small-group setting. There were five teams each
      presenting a different type of patient as assessed only from the CBCT data. The
      first model focused on the problem (e.g., an impacted tooth), while the second
      model focused on how to evaluate and use CBCT scans to determine the patient's
      primary problem. Based on surveys conducted at the end of each course, the
      majority of students felt they had gained a better understanding of CBCT.

PMID- 21890848
TI  - Inclusion of oral-systemic health in predoctoral/undergraduate curricula of
      pharmacy, nursing, and medical schools around the world: a preliminary study.
AB  - There is increasing evidence that oral health is a critical component of overall
      health and that poor oral health may lead to initiation or exacerbation of
      chronic inflammatory diseases/conditions and adverse pregnancy outcomes. Added to
      this is an increasing awareness that among non-dental health care professions
      curricula (e.g., medicine, nursing, pharmacy, and allied health) there is an
      apparent lack of information regarding the interrelationships between oral health
      and overall health or recognition of the significance of oral health in achieving
      and sustaining general health outcomes. This study explored the amount of
      information related to oral-systemic science currently being taught in the
      predoctoral/undergraduate professional curricula of pharmacy, nursing, and
      medical schools in English-speaking universities around the world. The Oral
      Systemic Health Educational Curriculum Survey was circulated online to associate
      or academic deans at medical, nursing, and pharmacy schools in universities
      across Canada, the United States, Europe, Asia, Australia, and New Zealand. The
      survey found that 53.7 percent of the respondents ranked the inclusion of oral
      systemic science as somewhat important, 51.2 percent reported no or limited
      requirements to incorporate oral health education within their curricula, and
      59.6 percent rated their current curricula in oral-systemic health as inadequate.
      The majority of students in these programs are not being instructed to examine
      the mouth, nor are they being taught how to perform an oral examination. Despite
      growing awareness of emerging evidence of oral-systemic relationships and
      recommendations that all health care providers should contribute to enhancing
      oral health, this knowledge base appears to be substantially deficient in the
      curricula of pharmacy, nursing, and medical students in many universities. This
      study provides the first formal documentation that the curricula of non-dental
      health care professions, specifically in medicine, nursing, and pharmacy, do not
      contain adequate content related to oral-systemic health.

PMID- 21890849
TI  - Measuring clinical productivity in community-based dental education programs.
AB  - Community-based dental education programs (CBDEPs) are an important part of the
      curriculum in many dental schools. This article describes the redesign of the
      CBDEP at the University of Kentucky College of Dentistry. As part of the
      formative evaluation of this CBDEP, information on clinical productivity was
      collected in order to educate intramural faculty members about the scope and
      extent of services provided in extramural sites; develop an understanding of the
      productivity expected; complement the intramural education by placing dental
      students in particular settings where they could enhance certain clinical
      disciplines; and serve as a decision making tool in the selection of sites that
      provide the richest clinical experiences. A total of 158 students participated in
      the CBDEP during the three years of our study (2006-08). Productivity per site
      was calculated based on total, mean, and median number of services provided,
      billing (utilizing Kentucky's Medicaid fees for 2006), and Relative Value Units
      (RVUs). A total of 26,202 services, $972,109 in billing, and 43,053 RVUs was
      generated by the students, with an average of 175 services, $6,481, and 287 RVUs
      per student. Four categories (restorative, oral surgery, preventive, and
      diagnostic) accounted for 88 percent of total RVUs for all sites and all years.
      Productivity measured with RVU was the highest at private practices. Students
      spent most of their time providing restorative and oral surgery services.
      Measuring clinical productivity can be an effective tool to establish benchmarks,
      improve the site selection process, and educate those skeptical about the
      benefits of extramural education. Such an evaluation will enable faculty and
      program administrators involved in CBDEP to make continuous improvements.

PMID- 21890850
TI  - Evaluation of a pilot bridging program to enable Australian dental therapists to
      treat adult patients.
AB  - This study evaluated a pilot educational bridging program designed to provide
      dental therapists in Australia with the appropriate knowledge and skills required
      to enable them to translate their current clinical scope of practice to adult
      patients. Ten dental therapists completed a bridging program consisting of forty
      two hours of didactic content, fourteen hours of clinical observation, forty-two
      hours of clinical practicum under direct supervision, and 105 hours of clinical
      experience with supervision by mentoring dentists. Process and impact evaluation
      was undertaken at various stages of the program by participants and supervising
      dentists. Self-reported confidence and knowledge for dental therapists had
      increased at the completion of the course. Supervising dentists reported high
      levels of knowledge for dental therapists after completing the course and said
      that the course adequately prepared the dental therapists to translate their
      current clinical scope of practice to treat adult patients. Eight of the ten
      participants successfully completed the assessment at the completion of the
      course and were permitted by the Dental Practice Board of Victoria to extend
      their clinical scope of practice to adult patients aged twenty-six years of age
      or more. The dental therapists thought that the educational model was relevant in
      developing their clinical skills. The evaluation indicates that this model is an
      effective method of extending the scope of practice for dental therapists and has
      important implications in enhancing the flexibility of the dental team.

PMID- 21890851
TI  - Health literacy impact on patient-provider interactions involving the treatment
      of dental problems.
AB  - Health literacy-related problems can interfere with effective doctor-patient
      communication and effective patient care. This study examined several health
      literacy-related markers for patients seeking treatment in hospital emergency
      departments and physician and dentist offices for dental problems and injuries.
      Participants consisted of low-income white, black, and Hispanic adults who had
      experienced a dental problem or injury during the previous twelve months and who
      visited a hospital emergency department, physician, or dentist for treatment. A
      stratified random sample of Maryland households participated in a cross-
      sectional telephone survey. Interviews were completed with 94.8 percent of 423
      eligible individuals. Multivariable logistic regression analyses were performed.
      Only 10.0 percent of the respondents expressed a difficulty understanding what
      they were told by the health provider, while 4.9 percent expressed a difficulty
      understanding the dental or medical forms they were asked to complete and 6.9
      percent reported that they had difficulty getting the health provider to
      understand their dental problem or injury. Logistic regression analysis found
      that males and Hispanics were significantly (p<0.05) more likely to experience
      health literacy-related problems. In general, respondents did not express health
      literacy-related problems. Additional research is needed to identify health
      literacy-related barriers to effective patient-provider communication.

PMID- 21890852
TI  - Medicaid patients in dental school clinics: do personal and professional
      experiences matter?
AB  - The purpose of this study was to explore dental and dental hygiene students' and
      faculty members' personal experiences with Medicaid prior to coming to dental
      school as well as their professional/educational experiences with patients on
      Medicaid during their dental/dental hygiene education and how these experiences
      relate to their professional attitudes and behavior concerning treating patients
      on Medicaid. Survey data were collected from 317 dental students, fifty-five
      dental hygiene students, and fifty-seven clinical faculty members at the
      University of Michigan. The results showed that while responding students'
      confidence concerning treating Medicaid patients increased over the course of
      their education, their intention to treat these patients actually decreased. The
      more personal experiences with Medicaid these students had before dental school,
      the more they enjoyed treating Medicaid patients, the more confident they were
      when treating these patients, and the more likely they were to treat these
      patients in the future. The more professional experiences these students had
      during dental school, the more they enjoyed treating Medicaid patients, and the
      more confident they were when treating these patients, but the less likely they
      were to treat them in the future. In conclusion, experiences with Medicaid before
      dental school as well as professional experiences during dental education
      correlated with later professional attitudes and behaviors. The implications of
      these findings for dental education are explored.

PMID- 21890853
TI  - Increasing predoctoral dental students' motivations to specialize in
      prosthodontics.
AB  - This study provides data about factors that influence dental students' decision
      of which specialty to pursue and describes program changes in prosthodontics
      designed to expand student interest in a prosthodontics training program. Of 176
      current and recently graduated students at Harvard School of Dental Medicine, 167
      responded to the e-mail survey for a 94.9 percent response rate. Using the
      Pearson chi-square analysis, we analyzed nine factors to determine their
      contribution to these students' choice of specialty. Two factors, lecture and
      faculty/mentoring, were highly significant (p<0.006) regarding impact on the
      students' introductory experience with prosthodontics. When choosing a specialty,
      44 percent of all students ranked "enjoyment of providing the specialty service"
      as the most important factor. Students wishing to specialize in prosthodontics,
      however, ranked four significant factors: enjoyment of providing the specialty
      service (p<0.037, p<0.057); faculty influence (p<0.0002, p<0.0001); length of
      program (p<0.039, p<0.006); and cost of program (p<0.023, p<0.004). Respondents
      also ranked the nine American Dental Association-recognized specialties regarding
      their perceptions of future salary and impact on the dental profession. They
      ranked prosthodontics fourth for future salary and fifth for impact on the
      profession. At the same time that this study was being conducted, key changes
      were being made in the graduate prosthodontics program; those appear to have had
      a positive impact on students' interest in pursuing prosthodontics as a
      specialty.

PMID- 21890854
TI  - Introduction of implants into postdoctoral endodontic residency programs.
AB  - The purpose of this study was to survey the directors of postdoctoral endodontic
      programs in the United States to ascertain their attitudes and approaches
      regarding incorporation of implants into the endodontic curriculum. We
      hypothesized that program directors would agree that implant training should be
      incorporated into the endodontic curriculum. We also hypothesized that they would
      all prefer apical surgeries and retreatment over implants when plausible. A
      twenty-item online survey was emailed to all fifty-two postdoctoral endodontic
      program directors in the United States. A 100 percent response was received. The
      results showed that 78.6 percent agreed that implant training should be
      incorporated, 85.7 percent preferred the didactic approach, and 42.9 percent
      preferred clinical implant training. One hundred percent preferred apical
      surgeries and retreatment over implants when plausible, and 53.8 percent did not
      prefer implants over endodontic treatment for teeth with a questionable
      prognosis. This survey indicates that implant training has been incorporated into
      postdoctoral endodontic programs and that the Commission on Dental Accreditation
      standards are being met. The trend may be to become more hands-on in the future
      if program directors believe there is a need to provide training in actual
      placement of implants.

PMID- 21890855
TI  - Computer-assisted dental simulation as a predictor of preclinical operative
      dentistry performance.
AB  - We tested whether a computerized dental simulator (CDS) pre-test could predict
      preclinical operative dentistry examination scores. Thirty-eight first-year
      students completed cavity preparations during a single four-hour CDS pre-test
      prior to the operative dentistry course and during subsequent practical
      examinations. Masked, calibrated faculty members scored the preparations in both
      settings. Pass rates for the CDS pre-test, Exam 1, and Exam 2 were 50 percent, 66
      percent, and 86 percent, respectively. Students who passed the CDS pre-test were
      more likely to pass Exam 1 (95 percent vs. 37 percent, p=0.0004) but not Exam 2
      (89 percent vs. 83 percent, p=0.66) and had better mean scores on Exam 1 (73.4
      vs. 68.3, p<0.0001), but not Exam 2 (76.2 vs. 74.7, p=0.35). As a diagnostic,
      success on the CDS pre-test predicted success on Exam 1 with 72 percent
      sensitivity and 92 percent specificity (positive predictive value 95 percent,
      negative predictive value 63 percent). As a diagnostic for Exam 2 performance,
      the CDS pre-test was a weaker predictor and not statistically significant. These
      findings suggest that a pre-course CDS test may help to identify students in need
      of early instructional intervention. Future studies are warranted to further
      define and implement the use of simulation technology in the assessment of
      students' psychomotor learning potential.

PMID- 21890856
TI  - Introduction of an implant surgical selective into a predoctoral dental
      curriculum.
AB  - This article describes the introduction of an implant surgical selective into a
      predoctoral dental curriculum. It outlines the various challenges encountered in
      developing the program and the methods used to overcome those challenges. The
      article also discusses the outcomes of the first year of the program.

PMID- 21890857
TI  - Teaching local anesthesia in dental schools: opinions about the student-to
      student administration model.
AB  - The student-to-student local anesthesia administration model has been an accepted
      part of the formal curriculum in dental schools for teaching this clinical skill.
      However, there is very little published literature that explores the validity of
      this model or examines students' attitudes toward it. The ethics of this
      educational model and the value of consent also need to be explored. In this
      study, an online survey regarding the student-to-student administration model was
      used to obtain the opinions of students and faculty members at three dental
      schools in one state of the United States. The survey was distributed by the
      Office of Academic Affairs at each school. A total of 152 individuals responded
      to this survey: 123 (80.9 percent) dental students and twenty-nine (19.1 percent)
      faculty members. The respondents consistently identified the perceived strengths
      of this model, while a number also identified the need for consent and raised
      ethical concerns. These findings highlight the complex nature of the respondents'
      opinions and raise the question of whether modification of this mode of
      instruction may be needed.

PMID- 21890858
TI  - Graduates' perceived preparedness for dental practice from PBL and traditional
      curricula.
AB  - The objective of this study was to compare dental graduates' perceived
      preparedness for practice after being educated in a problem-based learning (PBL)
      curriculum with those who graduated from a traditional undergraduate curriculum,
      both at the University of Hong Kong. A cohort of graduates from the traditional
      dental curriculum (1997-2001) and a cohort of graduates from the PBL curriculum
      (2004-08) rated their self-perceived preparedness for dental practice in fifty
      nine aspects of dentistry across nine domains. Perceived preparedness for dental
      practice was compared at domain and item levels (accounting for multiple
      comparisons) using chi-square statistics. Both cohorts felt well prepared for the
      "bread and butter" aspects of dentistry, but less so for specific specialty
      disciplines. There was no significant difference between PBL and traditional
      graduates' self-perceived preparedness in eight of the nine domains of dental
      practice (P>0.05). However, in the area of orthodontics, both cohorts felt ill
      prepared for practice and more so among the PBL cohort (P<0.01). For the most
      part, regardless of curriculum design, these dental graduates perceived
      themselves to be well prepared for dental practice.

PMID- 21890859
TI  - Training device for dental students to practice mirror-inverted movements.
AB  - The goal of this study was to explore whether the ability of precise mirror
      inverted movements can be learned and improved with the device Mirroprep and
      whether practice success can be transferred to the clinical situation. Three
      groups of students at different levels of dental study and different achievement
      levels were asked to perform a drawing exercise with indirect vision using
      Mirroprep. Further, the group of most senior students were asked whether the
      motor skills learned with this device were helpful in clinical tooth preparations
      by use of the dental mirror. According to the test results, we were able to show
      that mirror-inverted motor functions can be learned and improved by practice and
      that it is also helpful for performing tooth preparations. Because of this, it is
      deemed reasonable for students to start practicing with the training device
      during their preclinical studies and to have their skills tested.

PMID- 21890860
TI  - Towards a specific approach to education in dental ethics: a proposal for
      organising the topics of biomedical ethics for dental education.
AB  - Understanding dental ethics as a field separate from its much better known
      counterpart, medical ethics, is a relatively new, but necessary approach in
      bioethics. This need is particularly felt in dental education and establishing a
      curriculum specifically for dental ethics is a challenging task. Although certain
      topics such as informed consent and patient rights can be considered to be of
      equal importance in both fields, a number of ethical issues in dental practice
      are only remotely-if at all-relevant for medical practice. Therefore, any sound
      approach to education in dental ethics has to recognise the unique aspects of
      dental practice in order to meet the needs of dental students and prepare them
      for the ethical challenges they may face during their professional practice. With
      this goal in mind, this paper examines the approach of the authors to dental
      ethics education and proposes a system to organise the topics of biomedical
      ethics for dental education. While the authors' perspective is based on their
      experience in Turkey, the proposed system of classification is not a rigid one;
      it is open to interpretation in other contexts with different social, cultural
      and professional expectations. Therefore, the paper also aims to inspire
      discussion on the development of an ideal dental ethics curriculum at an
      international level.

PMID- 21890861
TI  - Plagued by kindness: contagious sympathy in Shakespearean drama.
AB  - This article considers Shakespeare's metaphors of transmission, contagion and
      infection in the light of period plague tracts, medical treatises and plague time
      literature. The author demonstrates how period conceptions of disease are
      predicated upon a notion of sympathetic transference and, consequently, how
      kindness, likeness and communication between characters in Shakespearean drama
      are complicated and fraught with period specific anxiety. This article situates
      Shakespearean literary texts within a precise historical and medical moment,
      considering how scientific conceptions contaminate dramatic text.

PMID- 21890862
TI  - Outcome measures in major trauma care: a review of current international trauma
      registry practice.
AB  - Multiple reports over the past 20 years have criticised the care delivered to
      major trauma patients in England. The setting up of regional trauma networks is
      well underway to address these deficiencies. Outcomes currently collected in
      major trauma are restricted to mortality rates and process measures; however,
      many patients are left with long-term disabilities and reduced quality of life
      (QoL), which are not measured at present. Trauma systems need to develop outcome
      measures that capture this important information to judge the quality of care and
      influence the development of services. This review aimed to identify the current
      practice of international trauma registries with regard to outcome measurement
      and review the literature surrounding these measures. An internet-based search of
      international trauma registry websites including data dictionaries and annual
      reports was carried out as well as a literature review to determine what outcome
      measures are routinely collected by trauma registries. All registries were found
      to look at mortality and process measures, but only one registry routinely
      collected morbidity outcome measures for both adults and children. There is a
      considerable amount of disability and reduced QoL in survivors of major trauma
      that lasts for years following the injury. At present only the Victorian State
      Trauma Registry collects outcome measures that evaluate the extent of this.
      English regional trauma networks and the Trauma Audit and Research Network have
      the opportunity to learn from this experience and routinely start to collect
      measures of outcome that can drive service improvement and reduce patient
      morbidity.

PMID- 21890863
TI  - Patients who leave emergency departments without being seen: literature review
      and English data analysis.
AB  - OBJECTIVES: The purpose of this review was to determine the rate of those that
      leave the emergency department (ED) without being seen and their reasons, to
      clarify if such behaviour poses a health risk, to analyse the impact initiatives
      have made on the leave without being seen (LWBS) rate, and to discuss the
      implications of using it as a national performance indicator within the NHS.
      METHODS: A combination of data sources was reviewed: a 'realistic' literature
      review, analysis of hospital episode statistics data from England and a local NHS
      trust audit. MAJOR FINDINGS: LWBS rates vary across the world, from 15% to 0.36%.
      Also initiatives to reduce LWBS rates demonstrated mixed outcomes, with
      reductions in the rate by as much as 96%, while others were ineffective. The most
      common reason quoted for LWBS was long waiting times and there were few data to
      suggest LWBS posed a risk to patient health. CONCLUSIONS: LWBS is an issue
      experienced in many countries that has responded in a varying manner to many
      initiatives in attempts to reduce it; however, it is clearly associated with the
      waiting times experienced in ED and therefore working within a packet of
      performance measures it would assess the effect of waiting times from another
      perspective.

PMID- 21890864
TI  - The effects of bed height and time on the quality of chest compressions delivered
      during cardiopulmonary resuscitation: a randomised crossover simulation study.
AB  - INTRODUCTION: The 2010 International Liaison Committee on Resuscitation gave a
      detailed update on best practice for cardiopulmonary resuscitation (CPR) with a
      discussion on appropriate patient and CPR provider position, based largely on
      expert opinion. The objective of this study was to ascertain robust evidence on
      the effect of bed height and fatigue on chest compression effectiveness. METHODS:
      A modified Laerdal manikin was connected to a Dragor ventilator (to measure
      intrathoracic pressures generated). The manikin was placed on a hospital trolley
      and CPR was performed by candidates at three different bed heights in a
      randomised order: (1) mid-thigh, (2) anterior superior iliac spine and (3)
      xiphisternum. Chest compressions were continuous and asynchronous with
      ventilation, and were allowed to continue for 30 s before recordings were taken.
      At the anterior superior iliac spine level, chest compressions were continued for
      2 min, when further measurements were taken. RESULTS: 101 subjects took part. The
      differences in intrathoracic pressures generated at different bed heights were
      compared using analysis of variance testing for multiple groups and were
      statistically significant for p<0.05. The authors also found that the
      effectiveness of CPR decreased 17% over a 2-minute period (p<0.05). CONCLUSIONS:
      The most effective bed height position, allowing CPR providers to achieve the
      highest intrathoracic pressures during CPR, was one where the patient's chest was
      in line with the CPR provider's mid-thigh. The provider performing CPR should
      change every 2 min.

PMID- 21890865
TI  - The prognostic usefulness of platelets in acute heart failure.

PMID- 21890866
TI  - NICE guidance for off-pump CABG: keep the pump primed.
AB  - Because of a desire to reduce the morbidity of a well-established and effective
      procedure for coronary artery disease, up to 30% of coronary bypass operations
      are being performed without the use of a heart-lung pump. Concerns remain about
      the quality of the coronary anastomoses and the completeness of
      revascularisation. Randomised trials have not disclosed the significant reduction
      in morbidity or mortality that the early enthusiasts had hoped for. Yet a number
      of non-randomised studies have shown clinical benefit with the avoidance of an
      extracorporeal circulation, but these studies have been criticised for potential
      bias in patient selection and management. Most surgeons have not yet adopted this
      technique and are waiting for more evidence.

PMID- 21890867
TI  - Almanac 2011: heart failure. The national society journals present selected
      research that has driven recent advances in clinical cardiology.

PMID- 21890868
TI  - Ambivalent effect of aortic stenosis on von Willebrand factor and thrombin
      generation. Is transvalvular gradient the guilty party?

PMID- 21890870
TI  - A common standard.

PMID- 21890869
TI  - Prevalence of Anderson-Fabry disease in patients with hypertrophic
      cardiomyopathy: the European Anderson-Fabry Disease survey.
AB  - OBJECTIVES: The prevalence of Anderson-Fabry disease (AFD) in patients presenting
      with unexplained left ventricular hypertrophy (LVH) is controversial. The aim of
      this study was to determine the prevalence of AFD in a large, consecutive cohort
      of patients with hypertrophic cardiomyopathy (HCM) using rapid mutation
      screening. DESIGN, SETTING AND PATIENTS: A European multicentre cross-sectional
      study involving 13 referral centres. Inclusion criteria for the study were: men
      aged at least 35 years and women aged at least 40 years with unexplained LVH
      (maximum left ventricular wall thickness >= 1.5 cm). All patients were screened
      using a denaturing high-performance liquid chromatography protocol for rapid
      mutation screening of the alpha-galactosidase A (alpha-Gal A) gene and, if a
      sequence variant was found, direct sequencing was performed. 1386 patients (63.9%
      men, mean age 57.9 +/- 12.0 years) were enrolled in the study. RESULTS: Seven
      (0.5%) patients (age 57.4 +/- 9.0 years (45-72); three (43%) men) had pathogenic
      alpha-galactosidase A mutations. Polymorphisms were identified in 283 patients
      (20.4%). Maximal left ventricular wall thickness in patients carrying a disease
      causing mutation was 18 +/- 2 mm (range 15-22); four patients had concentric LVH
      and the remainder had asymmetric septal hypertrophy. CONCLUSIONS: The prevalence
      of AFD gene mutations in a large, consecutive cohort of European patients with
      unexplained LVH is 0.5%.

PMID- 21890871
TI  - Development of an optical character recognition pipeline for handwritten form
      fields from an electronic health record.
AB  - BACKGROUND: Although the penetration of electronic health records is increasing
      rapidly, much of the historical medical record is only available in handwritten
      notes and forms, which require labor-intensive, human chart abstraction for some
      clinical research. The few previous studies on automated extraction of data from
      these handwritten notes have focused on monolithic, custom-developed recognition
      systems or third-party systems that require proprietary forms. METHODS: We
      present an optical character recognition processing pipeline, which leverages the
      capabilities of existing third-party optical character recognition engines, and
      provides the flexibility offered by a modular custom-developed system. The system
      was configured and run on a selected set of form fields extracted from a corpus
      of handwritten ophthalmology forms. OBSERVATIONS: The processing pipeline allowed
      multiple configurations to be run, with the optimal configuration consisting of
      the Nuance and LEADTOOLS engines running in parallel with a positive predictive
      value of 94.6% and a sensitivity of 13.5%. DISCUSSION: While limitations exist,
      preliminary experience from this project yielded insights on the generalizability
      and applicability of integrating multiple, inexpensive general-purpose third
      party optical character recognition engines in a modular pipeline.

PMID- 21890872
TI  - Prevalence of medication administration errors in two medical units with
      automated prescription and dispensing.
AB  - OBJECTIVE: To identify the frequency of medication administration errors and
      their potential risk factors in units using a computerized prescription order
      entry program and profiled automated dispensing cabinets. DESIGN: Prospective
      observational study conducted within two clinical units of the Gastroenterology
      Department in a 1537-bed tertiary teaching hospital in Madrid (Spain).
      MEASUREMENTS: Medication errors were measured using the disguised observation
      technique. Types of medication errors and their potential severity were
      described. The correlation between potential risk factors and medication errors
      was studied to identify potential causes. RESULTS: In total, 2314 medication
      administrations to 73 patients were observed: 509 errors were recorded (22.0%)-68
      (13.4%) in preparation and 441 (86.6%) in administration. The most frequent
      errors were use of wrong administration techniques (especially concerning food
      intake (13.9%)), wrong reconstitution/dilution (1.7%), omission (1.4%), and wrong
      infusion speed (1.2%). Errors were classified as no damage (95.7%), no damage but
      monitoring required (2.3%), and temporary damage (0.4%). Potential clinical
      severity could not be assessed in 1.6% of cases. The potential risk factors
      morning shift, evening shift, Anatomical Therapeutic Chemical medication class
      antacids, prokinetics, antibiotics and immunosuppressants, oral administration,
      and intravenous administration were associated with a higher risk of
      administration errors. No association was found with variables related to
      understaffing or nurse's experience. CONCLUSIONS: Medication administration
      errors persist in units with automated prescription and dispensing. We identified
      a need to improve nurses' working procedures and to implement a Clinical Decision
      Support tool that generates recommendations about scheduling according to dietary
      restrictions, preparation of medication before parenteral administration, and
      adequate infusion rates.

PMID- 21890873
TI  - Comparison of a basic and an advanced pharmacotherapy-related clinical decision
      support system in a hospital care setting in the Netherlands.
AB  - OBJECTIVE To compare the clinical relevance of medication alerts in a basic and
      in an advanced clinical decision support system (CDSS). DESIGN: A prospective
      observational study. MATERIALS AND METHODS: We collected 4023 medication orders
      in a hospital for independent evaluation in two pharmacotherapy-related decision
      support systems. Only the more advanced system considered patient characteristics
      and laboratory test results in its algorithms. Two pharmacists assessed the
      clinical relevance of the medication alerts produced. The alert was considered
      relevant if the pharmacist would undertake action (eg, contact the physician or
      the nurse). The primary analysis concerned the positive predictive value (PPV)
      for clinically relevant medication alerts in both systems. RESULTS: The PPV was
      significantly higher in the advanced system (5.8% vs 17.0%; p<0.05). Significant
      differences were found in the alert categories: drug-(drug) interaction (9.9% vs
      14.8%; p<0.05), drug-age interaction (2.9% vs 73.3%; p<0.05), and dosing guidance
      (5.6% vs 16.9%; p<0.05). Including laboratory values and other patient
      characteristics resulted in a significantly higher PPV for the advanced CDSS
      compared to the basic medication alerts (12.2% vs 23.3%; p<0.05). CONCLUSION: The
      advanced CDSS produced a higher proportion of clinically relevant medication
      alerts, but the number of irrelevant alerts remained high. To improve the PPV of
      the advanced CDSS, the algorithms should be optimized by identifying additional
      risk modifiers and more data should be made electronically available to improve
      the performance of the algorithms. Our study illustrates and corroborates the
      need for cyclic testing of technical improvements in information technology in
      circumstances representative of daily clinical practice.

PMID- 21890874
TI  - A clinical decision support needs assessment of community-based physicians.
AB  - OBJECTIVE: To conduct a grounded needs assessment to elicit community-based
      physicians' current views on clinical decision support (CDS) and its desired
      capabilities that may assist future CDS design and development for community
      based practices. MATERIALS AND METHODS: To gain insight into community-based
      physicians' goals, environments, tasks, and desired support tools, we used a
      human-computer interaction model that was based in grounded theory. We conducted
      30 recorded interviews with, and 25 observations of, primary care providers
      within 15 urban and rural community-based clinics across Oregon. Participants
      were members of three healthcare organizations with different commercial
      electronic health record systems. We used a grounded theory approach to analyze
      data and develop a user-centered definition of CDS and themes related to desired
      CDS functionalities. RESULTS: Physicians viewed CDS as a set of software tools
      that provide alerts, prompts, and reference tools, but not tools to support
      patient management, clinical operations, or workflow, which they would like. They
      want CDS to enhance physician-patient relationships, redirect work among staff,
      and provide time-saving tools. Participants were generally dissatisfied with
      current CDS capabilities and overall electronic health record usability.
      DISCUSSION: Physicians identified different aspects of decision-making in need of
      support: clinical decision-making such as medication administration and
      treatment, and cognitive decision-making that enhances relationships and
      interactions with patients and staff. CONCLUSION: Physicians expressed a need for
      decision support that extended beyond their own current definitions. To meet this
      requirement, decision support tools must integrate functions that align time and
      resources in ways that assist providers in a broad range of decisions.

PMID- 21890875
TI  - Effects of organic loading rate on reactor performance and archaeal community
      structure in mesophilic anaerobic digesters treating municipal sewage sludge.
AB  - In this study, the organic loading rate (OLR) of a high-solids anaerobic
      digestion (HSAD) system was increased from 3.4 to 5.0 gVS L(-1) day(-1) and
      reactor stability, performance and microbial community structure were determined.
      Laboratory simulations (3.5 L) of the full-scale process (500 dry ton year(-1))
      were conducted using continuously stirred-tank mesophilic reactors. OLRs of 3.4
      gVS L(-1)day(-1) (equal to the full-scale HSAD), 4.0, 4.5 and 5.0 gVS L(-1)day(
      1) were evaluated. Biochemical parameters and archaeal community dynamics were
      measured over 42 days of steady state operation. Results showed that increasing
      OLR increased the amount of organic matter conversion and resulted in higher
      organic matter removal and volumetric methane (CH4) production (VMP) rates. The
      highest volatile solids (VS) removal and VMP results of 54 +/- 2% and 1.4 +/- 0.1
      L CH4 L(-1)day(-1) were observed for 5.0 gVS L(-1) day(-1). The efficiency of
      reactor conversion of organic matter to CH(4) was found to be similar in all the
      treatments with an average value of 0.57 +/- 0.07 LCH(4) gVS(-1) (removed). 16S
      rRNA gene terminal restriction fragment polymorphism (T-RFLP) analyses revealed
      that archaeal TRFs remained stable during the experiment accounting for an
      average relative abundance (RA) of 81 +/- 1%. Archaea consistent with multiple
      terminal restriction fragments (TRFs) included members of the Euryarchaeota and
      Crenarchaeota phyla, including acetoclastic and hydrogenotrophic groups. In
      conclusion, this laboratory-scale study suggests that performance and stability
      as well as the archaeal community structure in this HSAD system was unaffected by
      increasing the OLR by nearly 50% and that this increase resulted in a similar
      increase in the amount of CH(4) gas generated.

PMID- 21890876
TI  - Bulky waste quantities and treatment methods in Denmark.
AB  - Bulky waste is a significant and increasing waste stream in Denmark. However,
      only little research has been done on its composition and treatment. In the
      present study, data about collection methods, waste quantities and treatment
      methods for bulky waste were obtained from two municipalities. In addition a
      sorting analysis was conducted on combustible waste, which is a major fraction of
      bulky waste in Denmark. The generation of bulky waste was found to be 150-250 kg
      capita(-1) year(-1), and 90% of the waste was collected at recycling centres; the
      rest through kerbside collection. Twelve main fractions were identified of which
      ten were recyclable and constituted 50-60% of the total quantity. The others were
      combustible waste for incineration (30-40%) and non-combustible waste for
      landfilling (10%). The largest fractions by mass were combustible waste, bricks
      and tile, concrete, non-combustible waste, wood, and metal scrap, which together
      made up more than 90% of the total waste amounts. The amount of combustible waste
      could be significantly reduced through better sorting. Many of the waste
      fractions consisted of composite products that underwent thorough separation
      before being recycled. The recyclable materials were in many cases exported to
      other countries which made it difficult to track their destination and further
      treatment.

PMID- 21890877
TI  - Cities as development drivers: from waste problems to energy recovery and climate
      change mitigation.
AB  - There is a strong connection between economic growth and development of cities.
      Economic growth tends to stimulate city growth, and city economies have often
      shaped innovative environments that in turn support economic growth.
      Simultaneously, social and environmental problems related to city growth can be
      serious threats to the realization of the socio-economic contributions that
      cities can make. However, as a result of considerable diversity of competences
      combined with interactive learning and innovation, cities may also solve these
      problems. The 'urban order' may form a platform for innovative problem solving
      and potential spill-over effects, which may stimulate further economic growth and
      development. This paper discusses how waste problems of cities can be transformed
      to become part of new, more sustainable solutions. Two cases are explored:
      Aalborg in Denmark and Malmo in Sweden. It is shown that the cities have the
      potential to significantly contribute to a more sustainable development through
      increased material recycling and energy recovery. Waste prevention may increase
      this potential. For example, instead of constituting 3% of the total greenhouse
      gas emission problem, it seems possible for modern European cities to contribute
      to greenhouse gas emission reduction by 15% through up to date technology and
      integrated waste management systems for material and energy recovery. Going from
      being part of the problem to providing solutions; however, is not an easy
      endeavour. It requires political will and leadership, supportive regulatory
      frameworks, realistic timetables/roadmaps, and a diverse set of stakeholders that
      can provide the right creative and innovative mix to make it possible.

PMID- 21890878
TI  - Improved detection of acute myocardial infarction in patients with chest pain and
      significant left main stem coronary stenosis.
AB  - BACKGROUND: Non-invasive diagnosis of acute myocardial infarction (AMI)
      associated with significant left main stem (LMS) stenosis remains challenging.
      METHODS: Consecutive patients presenting with acute ischaemic-type chest pain
      from 2000 to 2010 were analysed. Entry criteria: 12-lead ECG and Body Surface
      Potential Map (BSPM) at presentation, cardiac troponin T (cTnT) >=12 h and
      coronary angiography during admission. cTnT >=0.03 ug/l defined AMI. ECG
      abnormalities assessed: STEMI by Minnesota criteria; ST elevation (STE) aVR >=0.5
      mm; ST depression (STD) >=0.5 mm in >=2 contiguous leads (CL); T-wave inversion
      (TWI) >=1 mm in >=2 CL. BSPM STE was >=2 mm in anterior, >=1 mm in lateral,
      inferior, right ventricular or high right anterior and >=0.5 mm in posterior
      territories. Significant LMS stenosis was >=70%. RESULTS: Enrolled were 2810
      patients (aged 60 +/- 12 years; 71% male). Of these, 116 (4.1%) had significant
      LMS stenosis with AMI occurring in 92 (79%). STEMI by Minnesota criteria occurred
      in 13 (11%) (sensitivity 12%, specificity 92%), STE in lead aVR in 23 (20%)
      (sensitivity 23%, specificity 92%), TWI in 38 (33%) (sensitivity 34%, specificity
      71%) and STD in 51 (44%) (sensitivity 49%, specificity 75%). BSPM STE occurred in
      85 (73%): sensitivity 88%, specificity 83%, positive predictive value 95% and
      negative predictive value 65%. Of those with AMI, 74% had STE in either the high
      right anterior or right ventricular territories not identified by the 12-lead
      ECG. C-Statistic for AMI diagnosis using BSPM STE was 0.800 (P < 0.001).
      CONCLUSION: In patients with significant LMS stenosis presenting with chest pain,
      BSPM STE has improved sensitivity (88%), with specificity 83%, over 12-lead ECG
      in the diagnosis of AMI.

PMID- 21890879
TI  - Targeted systemic radiotherapy with scVEGF/177Lu leads to sustained disruption of
      the tumor vasculature and intratumoral apoptosis.
AB  - Tumor vessels abundantly express receptors for vascular endothelial growth factor
      (VEGF), despite treatment with conventional or antiangiogenic drugs. We wished to
      determine whether the high levels of VEGF receptor (VEGFR) within the tumor
      vasculature could be leveraged for intracellular delivery of therapeutically
      significant doses of scVEGF/(177)Lu, a novel radiopharmaceutical based on a
      recombinant single-chain (sc) derivative of VEGF, in orthotopic breast cancer
      models. METHODS: scVEGF-PEG (polyethylene gycol)-DOTA conjugates containing 2.0-,
      3.4-, or 5.0-kDa PEG linkers site-specifically conjugated to a cysteine
      containing tag (Cys-tag) in scVEGF were radiolabeled with (177)Lu
      (scVEGF/(177)Lu) for in vivo studies. Human MDA231luc and mouse 4T1luc cell lines
      were injected orthotopically to establish breast carcinoma tumors in
      immunodeficient and immunocompetent hosts, respectively. The effects of
      scVEGF/(177)Lu were defined by analysis of changes in tumor growth and
      immunohistochemical staining for the endothelial markers CD31 and VEGFR-2 and
      terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)
      staining for intratumoral apoptosis. RESULTS: Biodistribution assays and
      dosimetric calculations established that scVEGF/(177)Lu with a 3.4-kDa PEG linker
      delivered the highest dose of radiation to tumors (69.9 cGy/MBq/g of tissue) and
      the lowest dose to the kidneys (33.3 cGy/MBq/organ). Total doses below 40
      MBq/mouse of scVEGF/(177)Lu did not affect renal function, and 3 divided doses of
      6.3 MBq/mouse or a bolus dose of 18.9 MBq/mouse induced only transient
      lymphopenia and weight loss (<10% baseline weight). In mice with orthotopic
      mammary breast carcinoma, intravenous injections of well-tolerated bolus and
      fractionated doses of scVEGF/(177)Lu in the range from 6.3 to 18.9 MBq/mouse (25
      76 MBq/m(2)) resulted in dose-dependent tumor growth inhibition.
      Immunohistochemical analysis of tumors at 4-5 wk after single injections of
      scVEGF/(177)Lu indicated dose-dependent regression of tumor vasculature and
      widespread intratumoral apoptosis. A single dose of 7.4 MBq/mouse of
      scVEGF/(177)Lu given before a course of bevacizumab or sunitinib treatment
      enhanced the antiangiogenic effects of both drugs. CONCLUSION: Selective
      targeting of VEGFR in tumor vasculature with well-tolerated doses of
      scVEGF/(177)Lu is effective in orthotopic breast cancer models. As high levels of
      VEGFR expression in the tumor vasculature are a common feature in a variety of
      cancers, targeting tumor angiogenesis with scVEGF/(177)Lu warrants further
      exploration.

PMID- 21890880
TI  - 89Zr-nanocolloidal albumin-based PET/CT lymphoscintigraphy for sentinel node
      detection in head and neck cancer: preclinical results.
AB  - Identifying sentinel nodes near the primary tumor remains a problem in, for
      example, head and neck cancer because of the limited resolution of current
      lymphoscintigraphic imaging when using (99m)Tc-nanocolloidal albumin. This study
      describes the development and evaluation of a nanocolloidal albumin-based tracer
      specifically dedicated for high-resolution PET detection. METHODS: (89)Zr was
      coupled to nanocolloidal albumin via the bifunctional chelate p
      isothiocyanatobenzyldesferrioxamine B. Quality control tests, including particle
      size measurements, and in vivo biodistribution and imaging experiments in a
      rabbit lymphogenic metastasis model were performed. RESULTS: Coupling of (89)Zr
      to nanocolloidal albumin appeared to be efficient, resulting in a stable product
      with a radiochemical purity greater than 95%, without affecting the particle
      size. PET showed distinguished uptake of (89)Zr-nanocolloidal albumin in the
      sentinel nodes, with visualization of lymphatic vessels, and with a
      biodistribution comparable to (99m)Tc-nanocolloidal albumin. CONCLUSION: (89)Zr
      nanocolloidal albumin is a promising tracer for sentinel node detection by PET.

PMID- 21890881
TI  - Paradoxical embolism, stroke and sclerotherapy.
AB  - Sclerotherapy has been associated with 13 published cases of stroke since 1994.
      Four earlier reports implicated liquid sclerosants while nine recent cases have
      followed foam sclerotherapy. This adverse event represents a very rare
      complication of a very popular procedure. Ten of the 13 reported patients
      recovered completely with no long-term sequelae. A right-to-left shunt and in
      particular a patent foramen ovale (PFO) was the most consistent risk factor.
      Paradoxical gas emboli were observed in the brain-supplying or the intra-cranial
      arteries of five patients with an immediate onset of stroke after foam
      sclerotherapy. Paradoxical clot embolism was suspected in three patients with a
      delayed onset of stroke and concurrent venous thrombosis. In the remaining five
      cases, which included two cases with an immediate onset after liquid
      sclerotherapy, no specific cause was identified. Patients with a past history of
      cryptogenic stroke or a long life history of recurrent classic migraine attacks
      (with aura) have a higher risk of neurological adverse events and may benefit
      from preoperative screening and percutaneous closure of PFO.

PMID- 21890882
TI  - A mannequin study of intubation with the AP advance and GlideScope Ranger
      videolaryngoscopes and the Macintosh laryngoscope.
AB  - BACKGROUND: The AP Advance (APA) is a videolaryngoscope with interchangeable
      blades: intubators can choose standard Macintosh blades or a difficult-airway
      blade with increased curvature and a channel to guide the tube to the larynx. The
      APA may therefore be comparably effective in both normal and difficult airways.
      We tested the hypotheses that intubation with the APA is no slower than Macintosh
      laryngoscopy for normal mannequin airways, and that it is no slower than
      videolaryngoscopy using a GlideScope Ranger in difficult mannequin airways.
      METHODS: Medical professionals whose roles potentially include tracheal
      intubation were trained with each device. Participants intubated simulated
      (Laerdal SimMan) normal and difficult airways with the APA, GlideScope, and a
      conventional Macintosh blade. Speed of intubation was compared using Cox
      proportional hazards regression, with a hazard ratio >0.8 considered noninferior.
      We also compared laryngeal visualization, failures, and participant preferences.
      RESULTS: Unadjusted intubation times in the normal airway with the APA and
      Macintosh were virtually identical (median, 22 vs 23 seconds); after adjustment
      for effects of experience, order, and period, the hazard ratio (95% confidence
      interval) comparing APA with Macintosh laryngoscopy was 0.87 (0.65, 1.17), which
      was not significantly more than our predefined noninferiority boundary of 0.8 (P
      = 0.26). Intubation with the APA was faster than with the GlideScope in difficult
      airways (hazard ratio = 7.6 [5.0, 11.3], P < 0.001; median, 20 vs 59 seconds).
      All participants intubated the difficult airway mannequin with the APA, whereas
      33% and 37% failed with the GlideScope and Macintosh, respectively. In the
      difficult airway, 99% of participants achieved a Cormack and Lehane grade I to II
      view with the APA, versus 85% and 33% with the GlideScope and Macintosh,
      respectively. When asked to choose 1 device overall, 82% chose the APA.
      CONCLUSIONS: Intubation times were similar with the APA and Macintosh
      laryngoscopes in mannequins with normal airways. However, intubation with the APA
      was significantly faster than with the GlideScope in the difficult mannequin
      simulation.

PMID- 21890883
TI  - The effects of anesthetic preconditioning with sevoflurane in an experimental
      lung autotransplant model in pigs.
AB  - BACKGROUND: Ischemia-reperfusion lung injury is doubly important in thoracic
      surgery because of the associated ventilation damage to 1 lung. In this study we
      evaluated the cytoprotective effects of sevoflurane in a pulmonary autotransplant
      model in pigs. METHODS: Twenty Large White pigs undergoing pneumonectomy plus
      lung autotransplant were divided into 2 10-member groups on the basis of the
      anesthetic received (propofol or sevoflurane). Proinflammatory mediators,
      oxidative stress, nitric oxide metabolism, and hemodynamic and blood variables
      were measured at 5 different time points. RESULTS: There was an increase of
      oxidative stress markers and proinflammatory mediators in the propofol group,
      whereas the hemodynamic variables were similar in both groups. CONCLUSIONS: We
      demonstrated that sevoflurane decreased the inflammatory response and oxidative
      stress in a live ischemia-reperfusion lung model.

PMID- 21890884
TI  - Propofol in a modified cyclodextrin formulation: first human study of dose
      response with emphasis on injection pain.
AB  - BACKGROUND: A new lipid-free preparation of propofol has been developed
      containing the drug, sulfobutylether beta-cyclodextrin and water. The primary
      objective of this study was to compare the effects of propofol in the lipid
      formulation with those of the new cyclodextrin formulation, particularly with
      regard to pain on injection. We hypothesized that the propofol in cyclodextrin
      would be associated with less pain on injection than propofol in lipid. METHODS:
      The study was a single-center, double-blind, 2-period, randomized, dose
      escalating study using a completely balanced cross-over design in healthy
      volunteers. Pain on injection was compared between propofol in cyclodextrin and
      propofol in lipid using subject and observer assessments of pain rated at several
      different time points. Five response variables to pain were analyzed. RESULTS:
      Propofol in cyclodextrin had significantly higher pain scores for all 5
      variables. Other endpoints, including sedation, showed no difference. CONCLUSION:
      The propofol in cyclodextrin formulation failed to reduce the pain on injection
      associated with propofol.

PMID- 21890885
TI  - The optimal dose of prophylactic intravenous naloxone in ameliorating opioid
      induced side effects in children receiving intravenous patient-controlled
      analgesia morphine for moderate to severe pain: a dose finding study.
AB  - BACKGROUND: Opioid-induced side effects, such as pruritus, nausea, and vomiting
      are common and may be more debilitating than pain itself. A continuous low-dose
      naloxone infusion (0.25 MUg/kg/h) ameliorates some of these side effects in many
      but not all patients without adversely affecting analgesia. We sought to
      determine the optimal dose of naloxone required to minimize opioid-induced side
      effects and to measure plasma morphine and naloxone levels in a dose escalation
      study. METHODS: Fifty-nine pediatric patients (24 male/35 female; average age
      14.2 +/- 2.2 years) experiencing moderate to severe postoperative pain were
      started on IV patient-controlled analgesia morphine (basal infusion 20 MUg/kg/h,
      demand dose 20 MUg/kg, 5 doses/h) and a low-dose naloxone infusion (initial
      cohort: 0.05 MUg/kg/h; subsequent cohorts: 0.10, 0.15, 0.25, 0.40, 0.65, 1, and
      1.65 MUg/kg/h). If 2 patients developed intolerable nausea, vomiting, or
      pruritus, the naloxone infusion was increased for subsequent patients.
      Dose/treatment success occurred when 10 patients had minimal side effects at a
      naloxone dose. Blood samples were obtained for measurement of plasma morphine and
      naloxone levels after initiation of the naloxone infusion, processed, stored, and
      measured by tandem mass spectrometry with electrospray positive ionization.
      RESULTS: The minimum naloxone dose at which patients were successfully treated
      with a <10% side effect/failure rate was 1 MUg/kg/h; cohort size varied between 4
      and 11 patients. Naloxone was more effective in preventing pruritus than nausea
      and vomiting. Concomitant use of supplemental medicines to treat opioid-induced
      side effects was required at all naloxone infusion rates. Plasma naloxone levels
      were below the level of assay quantification (0.1 ng/mL) for infusion rates
      <=0.15 MUg/kg/h. At rates >0.25 MUg/kg/h, plasma levels increased linearly with
      increasing infusion rate. In each dose cohort, patients who failed therapy had
      comparable or higher plasma naloxone levels than those levels measured in
      patients who did not fail treatment. Plasma morphine levels ranged between 3.52
      and 172 ng/mL, and >90% of levels ranged between 10.2 and 61.6 ng/mL. Plasma
      morphine levels were comparable between patients who failed therapy and those
      patients who achieved symptom control. CONCLUSIONS: Naloxone infusion rates >=1
      MUg/kg/h significantly reduced, but did not eliminate, the incidence of opioid
      induced side effects in postoperative pediatric patients receiving IV patient
      controlled analgesia morphine. Patients who failed therapy generally had plasma
      naloxone and morphine levels that were comparable to those who had good symptom
      relief suggesting that success or failure to ameliorate opioid-induced side
      effects was unrelated to plasma levels.

PMID- 21890886
TI  - Maternal cardiac output changes after crystalloid or colloid coload following
      spinal anesthesia for elective cesarean delivery: a randomized controlled trial.
AB  - BACKGROUND: Minimizing hypotension associated with spinal anesthesia for cesarean
      delivery by administration of IV fluids and vasopressors reduces fetal and
      maternal morbidity. Most studies have concentrated on noninvasive systolic blood
      pressure (SBP) measurements to evaluate the effect of such regimens. We used a
      suprasternal Doppler flow technique to measure maternal cardiac output (CO)
      variables in parturients receiving a phenylephrine infusion combined with the
      rapid administration of crystalloid or colloid solution at the time of initiation
      of anesthesia (coload). We hypothesized that a colloid coload compared with a
      crystalloid coload would produce a larger sustained increase in CO and therefore
      reduce vasopressor requirements. METHODS: We recruited 60 healthy term women
      scheduled for elective cesarean delivery under spinal anesthesia for this
      randomized double-blind study. Baseline heart rate, baseline SBP, and CO
      variables including stroke volume, corrected flow time, and contractility were
      recorded in the left lateral tilt position. At the time of spinal injection,
      subjects were allocated to receive a rapid 1-L coload of either 6% w/v
      hydroxyethyl starch solution (HES) or Hartmann (crystalloid) solution (HS). A
      phenylephrine infusion was titrated to maintain maternal baseline SBP. CO was
      measured at 5-minute intervals for 20 minutes after initiation of spinal
      anesthesia. The primary outcome, CO, was compared between groups, as were
      secondary outcomes: phenylephrine dose and maternal hemodynamic and fetal outcome
      data. RESULTS: Maternal demographics, surgical times, and fetal outcome data were
      similar between groups. There were no significant differences between groups in
      any measured CO variable at any time point. CO was transiently higher than
      baseline at 5 minutes in the HS group and at 5 and 10 minutes in the HES group
      (range, 0.13-1.74 L/min); the overall mean difference in CO between crystalloid
      and colloid over the study period was 0.06 L/min (95% confidence interval: -0.46
      to 0.58). Stroke volume was higher than baseline in both groups throughout; peak
      velocity was consistently higher than baseline only in the HES group; and
      corrected flow time increased in both groups; the effect was transient in the HS
      but sustained in the HES group. Heart rate was not different at any time point
      within or between groups but did decrease over time. The total phenylephrine dose
      from time of spinal anesthesia to delivery was similar between groups.
      CONCLUSION: We found no difference in CO in women randomized to colloid or
      crystalloid coload. In addition, there were no differences in vasopressor
      requirements or hemodynamic stability. We conclude that there is no advantage in
      using colloid over crystalloid when used in combination with a phenylephrine
      infusion during spinal anesthesia for elective cesarean delivery.

PMID- 21890887
TI  - Does the baricity of bupivacaine influence intrathecal spread in the prolonged
      sitting position before elective cesarean delivery? A prospective randomized
      controlled study.
AB  - BACKGROUND: Difficulties in inserting an epidural catheter while performing
      combined spinal-epidural anesthesia for cesarean delivery may lead to undue
      delays between the spinal injection of the local anesthetic mixture and the
      adoption of the supine position with lateral tilt. We hypothesized that this
      delay may affect the intrathecal distribution of local anesthetic of different
      baricities such that hypobaric local anesthetic would lead to a higher sensory
      block level. METHODS: Healthy parturients with uncomplicated pregnancies
      undergoing elective cesarean delivery under combined spinal-epidural anesthesia
      were enrolled in this prospective double-blind randomized controlled trial. The
      subjects were allocated to receive hyperbaric (hyperbaric group), isobaric
      (isobaric group), or hypobaric (hypobaric group) spinal bupivacaine 10 mg. After
      the spinal injection, the subjects remained in the sitting position for 5 minutes
      (to simulate difficulty in inserting the epidural catheter) before being helped
      into the supine lateral tilt position. The primary outcome was the sensory block
      level during the 25 minutes after the spinal injection. Other end points included
      motor block score, maternal hypotension, and vasopressor requirements. RESULTS:
      Data from 89 patients were analyzed. Patient characteristics were similar in all
      groups. The median [interquartile range] (95% confidence interval) sensory levels
      after spinal injection were significantly higher with decreasing baricity:
      hyperbaric T10 [T11-8] (T10-9), isobaric T9 [T10-7] (T9-7), and hypobaric T6 [T8
      4] (T8-5) (P < 0.001, Cuzick trend). All patients in the hypobaric group reached
      a sensory block level of T4 at 25 minutes after spinal injection compared with
      80% of the patients in both the isobaric and hyperbaric groups (P = 0.04;
      difference 20%, 95% confidence interval of difference 4%-33%). Significantly more
      patients in the hypobaric group had complete lower limb motor block (Bromage
      score = 4) (hyperbaric 43%, isobaric 63%, and hypobaric 90%; P < 0.001). The
      incidences of maternal hypotension and nausea and vomiting were similar among
      groups, although the ephedrine requirements were significantly increased in the
      isobaric and hypobaric groups by factors of 1.83 and 3.0, respectively, compared
      with the hyperbaric group (P < 0.001, Cuzick trend). CONCLUSIONS: We demonstrated
      that when parturients undergoing cesarean delivery were maintained in the sitting
      position for 5 minutes after spinal injection of the local anesthetic, hypobaric
      bupivacaine resulted in sensory block levels that were higher compared with
      isobaric and hyperbaric bupivacaine, respectively, during the study period.

PMID- 21890888
TI  - Reversal of clopidogrel-induced bleeding with rFVIIa in healthy subjects: a
      randomized, placebo-controlled, double-blind, exploratory study.
AB  - BACKGROUND: Clopidogrel (Plavix(r)) therapy, although effective for minimizing
      risk of thrombotic events, is also associated with potential bleeding risk.
      Recombinant activated FVII (rFVIIa, NovoSeven(r)) induces hemostasis in
      hemophilia patients with inhibitors (alloantibodies) and has been proposed as
      potential treatment for mitigating clopidogrel therapy-mediated bleeding.
      METHODS: In this single-center, randomized, placebo-controlled, double-blind,
      dose-escalation, exploratory phase I trial, we assessed the safety and effects of
      rFVIIa in reversing clopidogrel-enhanced bleeding in an experimentally induced
      punch biopsy in healthy subjects. Efficacy assessments included the reversal of
      bleeding characteristics (bleed duration [BD], the primary end point and blood
      loss volume [BV] induced by punch biopsy, and thromboelastograph [TEG(r)]
      parameters) with rFVIIa or placebo after clopidogrel treatment. RESULTS: A
      significant number of subjects (56%) had limited response to clopidogrel (defined
      as <=30% platelet aggregation inhibition) and were discontinued from study. The
      remaining subjects continued and had 4 biopsies. Of 40 subjects randomized, 37
      were evaluated for efficacy. Clopidogrel treatment increased BD and BV compared
      with the baseline biopsy. Recombinant FVIIa (10 and 20 MUg/kg) significantly
      mitigated the clopidogrel-induced effects on BV (P = 0.007 and P = 0.001,
      respectively). Early trial termination limited the evaluation of effects of
      higher rFVIIa doses. Subgroup analyses of subjects biopsied by the same physician
      demonstrated significant reduction of clopidogrel-induced BD with 20 MUg/kg
      rFVIIa (P = 0.048). Ex vivo analysis of rFVIIa demonstrated clotting dynamics
      presented by parameters time to clot onset (TEG(r)-R) and clot angle (TEG(r)-A)
      (P < 0.005). CONCLUSIONS: In this clinical study, rFVIIa (10 and 20 MUg/kg)
      reversed the effect of clopidogrel on blood loss.

PMID- 21890889
TI  - A comparison between remifentanil and meperidine for labor analgesia: a
      systematic review.
AB  - BACKGROUND: Remifentanil is an ultrashort-acting opioid with favorable
      pharmacokinetic properties that make it suitable as a labor analgesic. Although
      it crosses the placenta freely, it is eliminated quickly in the neonate by rapid
      metabolism and redistribution. We aimed to determine whether remifentanil
      compared with meperidine is effective in reducing pain scores in laboring
      parturients. Other effects on the mother, the labor process, and the neonate were
      also examined. METHODS: MEDLINE, CINAHL, Embase, Cochrane CENTRAL, and Maternity
      and Infant Care databases were searched without language restriction using
      multiple keywords for labor analgesia, remifentanil, and meperidine. Published
      abstracts from 5 key research meetings and references from retrieved articles
      were examined for additional studies. Randomized controlled trials in laboring
      parturients comparing remifentanil with meperidine were selected. Risk of bias
      was assessed using criteria outlined in the Cochrane Handbook for Systematic
      Reviews of Interventions. We assessed for adequacy of sequence generation,
      allocation concealment, blinding, and completeness of follow-up. Data were
      extracted from each study using a standardized data collection form. The primary
      outcome was reduction in pain scores (visual analog scale [VAS], 0-100 mm). We
      also evaluated maternal side effects (sedation, oxygen desaturation, and
      bradypnea) and effects on the neonate (Apgar scores, umbilical cord pH, and
      Neurologic and Adaptive Capacity Scores). RESULTS: Seven studies (349 patients)
      were identified for inclusion; only 3 studies were suitable for quantitative
      synthesis in a meta-analysis (233 patients). We found that remifentanil reduces
      the mean VAS score at 1 hour by 25 mm more than meperidine (P < 0.001) (95%
      confidence interval = 19-31 mm). Limited conclusions can be made regarding the
      side-effect profile of remifentanil because of insufficient data. CONCLUSION:
      Compared with meperidine, remifentanil is superior in reducing mean VAS scores
      for labor pain after 1 hour.

PMID- 21890890
TI  - Arterial waveform analysis for the anesthesiologist: past, present, and future
      concepts.
AB  - Qualitative arterial waveform analysis has been in existence for millennia;
      quantitative arterial waveform analysis techniques, which can be traced back to
      Euler's work in the 18th century, have not been widely used by anesthesiologists
      and other clinicians. This is likely attributable, in part, to the widespread use
      of the sphygmomanometer, which allows the practitioner to assess arterial blood
      pressure without having to develop a sense for the higher-order characteristics
      of the arterial waveform. The 20-year delay in the development of devices that
      measure these traits is a testament to the primitiveness of our appreciation for
      this information. The shape of the peripheral arterial pressure waveform may
      indeed contain information useful to the anesthesiologist and intensivist. The
      maximal slope of the peripheral arterial pressure tracing seems to be related to
      left ventricular contractility, although the relationship may be confounded by
      other hemodynamic variables. The area under the peripheral arterial pressure
      tracing is related to stroke volume when loading conditions are stable; this
      finding has been used in the development of several continuous cardiac output
      monitors. Pulse wave velocity may be related to vascular impedance and could
      potentially improve the accuracy of waveform-based stroke volume estimates.
      Estimates of central arterial pressures (e.g., aortic) can be produced from
      peripheral (e.g., brachial, radial) tracings using a Generalized Transfer
      Function, and are incorporated into the algorithms of several continuous cardiac
      output monitors.

PMID- 21890891
TI  - New functional ligands for ficolin-3 among lipopolysaccharides of Hafnia alvei.
AB  - Ficolin-1 (M), ficolin-2 (L), ficolin-3 (H) and mannan-binding lectin (MBL)
      activate the complement system and have opsonic activity. The specificity of
      ficolin-3 is poorly characterized and currently limited to a few ligands only. We
      present new specific targets for human ficolin-3, identified among
      lipopolysaccharides (LPSs, endotoxin) of Hafnia alvei. The interaction was
      restricted to LPSs of four strains: 23, Polish Collection of Microorganisms (PCM)
      1200, PCM 1203 and PCM 1205 and limited to their O-specific polysaccharides (O
      specific PSs) composed of different numbers of oligosaccharide (OS) repeating
      units (RUs). Moreover, these LPS/ficolin-3 complexes activated the lectin pathway
      of complement in a C4b-deposition assay in a calcium- and magnesium-dependent
      way. A neoglycoconjugate of the O-specific PS fraction of H. alvei 1200 LPS with
      bovine serum albumin (BSA) was prepared and used as a tool for the determination
      of ficolin-3 concentration and activity in serum. To confirm a structure of the O
      specific PS 1200 selected for the conjugate preparation, structural analysis was
      performed on a series of O-specific PSs released by the mild acid hydrolysis of
      the LPS. The isolated O-specific PSs, showing the different length distributions,
      were devoid of a major part of the core OS region and had Hep-Kdo disaccharide at
      a reducing end. The neoglycoconjugate was a highly selective tool for the
      determination of ficolin-3 concentration and activity in serum (lectin pathway
      activation in the C4b deposition assay) and was not affected by MBL, ficolin-1
      and ficolin-2 or natural antibodies.

PMID- 21890892
TI  - Ncam1a and Ncam1b: two carriers of polysialic acid with different functions in
      the developing zebrafish nervous system.
AB  - Polysialic acid (polySia) is mainly described as a glycan modification of the
      neural cell adhesion molecule NCAM1. PolySia-NCAM1 has multiple functions during
      the development of vertebrate nervous systems including axon extension and
      fasciculation. Phylogenetic analyses reveal the presence of two related gene
      clusters, NCAM1 and NCAM2, in tetrapods and fishes. Within the ncam1 cluster,
      teleost fishes express ncam1a (ncam) and ncam1b (pcam) as duplicated paralogs
      which arose from a second round of ray-finned fish-specific genome duplication.
      Tetrapods, in contrast, express a single NCAM1 gene. Using the zebrafish model,
      we identify Ncam1b as a novel major carrier of polySia in the nervous system.
      PolySia-Ncam1a is expressed predominantly in rostral regions of the developing
      nervous system, whereas polySia-Ncam1b prevails caudally. We show that ncam1a and
      ncam1b have different expression domains which only partially overlap.
      Furthermore, Ncam1a and Ncam1b and their polySia modifications serve different
      functions in axon guidance. Formation of the posterior commissure at the
      forebrain/midbrain junction requires polySia-Ncam1a on the axons for proper
      fasciculation, whereas Ncam1b, expressed by midbrain cell bodies, serves as an
      instructive guidance cue for the dorso-medially directed growth of axons. Spinal
      motor axons, on the other hand, depend on axonally expressed Ncam1b for correct
      growth toward their target region. Collectively, these findings suggest that the
      genome duplication in the teleost lineage has provided the basis for a functional
      diversification of polySia carriers in the nervous system.

PMID- 21890893
TI  - SIRT1 links CIITA deacetylation to MHC II activation.
AB  - Antigen-dependent stimulation of T cells plays a critical role in adaptive
      immunity and host defense. Activation of major histocompatibility complex II (MHC
      II) molecules, dictated by Class II transactivator (CIITA), is considered a
      pivotal step in this process. The mechanism underlying differential regulation of
      CIITA activity by the post-translational modification machinery (PTM) and its
      implications are not clearly appreciated. Here, we report that SIRT1, a type III
      deacetylase, interacts with and deacetylates CIITA. SIRT1 activation augments MHC
      II transcription by shielding CIITA from proteasomal degradation and promoting
      nuclear accumulation and target binding of CIITA. In contrast, depletion of SIRT1
      upregulates CIITA acetylation and attenuates its activity. Nicotinamide
      phosphoribosyltransferase (NAMPT) that synthesizes NAD(+) required for SIRT1
      activation exerts similar effects on CIITA activity. Two different types of
      stress stimuli, hypobaric hypoxia and oxidized low-density lipoprotein (oxLDL),
      induce the acetylation of CIITA and suppress its activity by inhibiting the SIRT1
      expression and activity. Thus, our data link SIRT1-mediated deacetylation of
      CIITA to MHC II transactivation in macrophages and highlight a novel strategy
      stress cues may employ to manipulate host adaptive immune system.

PMID- 21890894
TI  - Signal-induced Brd4 release from chromatin is essential for its role transition
      from chromatin targeting to transcriptional regulation.
AB  - Bromodomain-containing protein Brd4 is shown to persistently associate with
      chromosomes during mitosis for transmitting epigenetic memory across cell
      divisions. During interphase, Brd4 also plays a key role in regulating the
      transcription of signal-inducible genes by recruiting positive transcription
      elongation factor b (P-TEFb) to promoters. How the chromatin-bound Brd4 transits
      into a transcriptional regulation mode in response to stimulation, however, is
      largely unknown. Here, by analyzing the dynamics of Brd4 during ultraviolet or
      hexamethylene bisacetamide treatment, we show that the signal-induced release of
      chromatin-bound Brd4 is essential for its functional transition. In untreated
      cells, almost all Brd4 is observed in association with interphase chromatin. Upon
      treatment, Brd4 is released from chromatin, mostly due to signal-triggered
      deacetylation of nucleosomal histone H4 at acetylated-lysine 5/8 (H4K5ac/K8ac).
      Through selective association with the transcriptional active form of P-TEFb that
      has been liberated from the inactive multi-subunit complex in response to
      treatment, the released Brd4 mediates the recruitment of this active P-TEFb to
      promoter, which enhances transcription at the stage of elongation. Thus, through
      signal-induced release from chromatin and selective association with the active
      form of P-TEFb, the chromatin-bound Brd4 switches its role to mediate the
      recruitment of P-TEFb for regulating the transcriptional elongation of signal
      inducible genes.

PMID- 21890895
TI  - OPM database and PPM web server: resources for positioning of proteins in
      membranes.
AB  - The Orientations of Proteins in Membranes (OPM) database is a curated web
      resource that provides spatial positions of membrane-bound peptides and proteins
      of known three-dimensional structure in the lipid bilayer, together with their
      structural classification, topology and intracellular localization. OPM currently
      contains more than 1200 transmembrane and peripheral proteins and peptides from
      approximately 350 organisms that represent approximately 3800 Protein Data Bank
      entries. Proteins are classified into classes, superfamilies and families and
      assigned to 21 distinct membrane types. Spatial positions of proteins with
      respect to the lipid bilayer are optimized by the PPM 2.0 method that accounts
      for the hydrophobic, hydrogen bonding and electrostatic interactions of the
      proteins with the anisotropic water-lipid environment described by the dielectric
      constant and hydrogen-bonding profiles. The OPM database is freely accessible at
      http://opm.phar.umich.edu. Data can be sorted, searched or retrieved using the
      hierarchical classification, source organism, localization in different types of
      membranes. The database offers downloadable coordinates of proteins and peptides
      with membrane boundaries. A gallery of protein images and several visualization
      tools are provided. The database is supplemented by the PPM server
      (http://opm.phar.umich.edu/server.php) which can be used for calculating spatial
      positions in membranes of newly determined proteins structures or theoretical
      models.

PMID- 21890896
TI  - Role of sequence encoded kappaB DNA geometry in gene regulation by Dorsal.
AB  - Many proteins of the Rel family can act as both transcriptional activators and
      repressors. However, mechanism that discerns the 'activator/repressor' functions
      of Rel-proteins such as Dorsal (Drosophila homologue of mammalian NFkappaB) is
      not understood. Using genomic, biophysical and biochemical approaches, we
      demonstrate that the underlying principle of this functional specificity lies in
      the 'sequence-encoded structure' of the kappaB-DNA. We show that Dorsal-binding
      motifs exist in distinct activator and repressor conformations. Molecular
      dynamics of DNA-Dorsal complexes revealed that repressor kappaB-motifs typically
      have A-tract and flexible conformation that facilitates interaction with co
      repressors. Deformable structure of repressor motifs, is due to changes in the
      hydrogen bonding in A:T pair in the 'A-tract' core. The sixth nucleotide in the
      nonameric kappaB-motif, 'A' (A(6)) in the repressor motifs and 'T' (T(6)) in the
      activator motifs, is critical to confer this functional specificity as A(6) ->
      T(6) mutation transformed flexible repressor conformation into a rigid activator
      conformation. These results highlight that 'sequence encoded kappaB DNA-geometry'
      regulates gene expression by exerting allosteric effect on binding of Rel
      proteins which in turn regulates interaction with co-regulators. Further, we
      identified and characterized putative repressor motifs in Dl-target genes, which
      can potentially aid in functional annotation of Dorsal gene regulatory network.

PMID- 21890897
TI  - Activity, specificity and structure of I-Bth0305I: a representative of a new
      homing endonuclease family.
AB  - Novel family of putative homing endonuclease genes was recently discovered during
      analyses of metagenomic and genomic sequence data. One such protein is encoded
      within a group I intron that resides in the recA gene of the Bacillus
      thuringiensis 03058-36 bacteriophage. Named I-Bth0305I, the endonuclease cleaves
      a DNA target in the uninterrupted recA gene at a position immediately adjacent to
      the intron insertion site. The enzyme displays a multidomain, homodimeric
      architecture and footprints a DNA region of ~60 bp. Its highest specificity
      corresponds to a 14-bp pseudopalindromic sequence that is directly centered
      across the DNA cleavage site. Unlike many homing endonucleases, the specificity
      profile of the enzyme is evenly distributed across much of its target site, such
      that few single base pair substitutions cause a significant decrease in cleavage
      activity. A crystal structure of its C-terminal domain confirms a nuclease fold
      that is homologous to very short patch repair (Vsr) endonucleases. The domain
      architecture and DNA recognition profile displayed by I-Bth0305I, which is the
      prototype of a homing lineage that we term the 'EDxHD' family, are distinct from
      previously characterized homing endonucleases.

PMID- 21890898
TI  - Novel dimeric structure of phage phi29-encoded protein p56: insights into uracil
      DNA glycosylase inhibition.
AB  - Protein p56 encoded by the Bacillus subtilis phage phi29 inhibits the host uracil
      DNA glycosylase (UDG) activity. To get insights into the structural basis for
      this inhibition, the NMR solution structure of p56 has been determined. The
      inhibitor defines a novel dimeric fold, stabilized by a combination of polar and
      extensive hydrophobic interactions. Each polypeptide chain contains three
      stretches of anti-parallel beta-sheets and a helical region linked by three short
      loops. In addition, microcalorimetry titration experiments showed that it forms a
      tight 2:1 complex with UDG, strongly suggesting that the dimer represents the
      functional form of the inhibitor. This was further confirmed by the functional
      analysis of p56 mutants unable to assemble into dimers. We have also shown that
      the highly anionic region of the inhibitor plays a significant role in the
      inhibition of UDG. Thus, based on these findings and taking into account previous
      results that revealed similarities between the association mode of p56 and the
      phage PBS-1/PBS-2-encoded inhibitor Ugi with UDG, we propose that protein p56
      might inhibit the enzyme by mimicking its DNA substrate.

PMID- 21890899
TI  - Identification and remediation of biases in the activity of RNA ligases in small
      RNA deep sequencing.
AB  - Deep sequencing of small RNAs (sRNA-seq) is now the gold standard for small RNA
      profiling and discovery. Biases in sRNA-seq have been reported, but their
      etiology remains unidentified. Through a comprehensive series of sRNA-seq
      experiments, we establish that the predominant cause of the bias is the RNA
      ligases. We further demonstrate that RNA ligases have strong sequence-specific
      biases which distort the small RNA profiles considerably. We have devised a
      pooled adapter strategy to overcome this bias, and validated the method through
      data derived from microarray and qPCR. In light of our findings, published small
      RNA profiles, as well as barcoding strategies using adapter-end modifications,
      may need to be revisited. Importantly, by providing a wide spectrum of substrate
      for the ligase, the pooled-adapter strategy developed here provides a means to
      overcome issues of bias, and generate more accurate small RNA profiles.

PMID- 21890900
TI  - Influence of ground-state structure and Mg2+ binding on folding kinetics of the
      guanine-sensing riboswitch aptamer domain.
AB  - Riboswitch RNAs fold into complex tertiary structures upon binding to their
      cognate ligand. Ligand recognition is accomplished by key residues in the binding
      pocket. In addition, it often crucially depends on the stability of peripheral
      structural elements. The ligand-bound complex of the guanine-sensing riboswitch
      from Bacillus subtilis, for example, is stabilized by extensive interactions
      between apical loop regions of the aptamer domain. Previously, we have shown that
      destabilization of this tertiary loop-loop interaction abrogates ligand binding
      of the G37A/C61U-mutant aptamer domain (Gsw(loop)) in the absence of Mg(2+).
      However, if Mg(2+) is available, ligand-binding capability is restored by a
      population shift of the ground-state RNA ensemble toward RNA conformations with
      pre-formed loop-loop interactions. Here, we characterize the striking influence
      of long-range tertiary structure on RNA folding kinetics and on ligand-bound
      complex structure, both by X-ray crystallography and time-resolved NMR. The X-ray
      structure of the ligand-bound complex reveals that the global architecture is
      almost identical to the wild-type aptamer domain. The population of ligand
      binding competent conformations in the ground-state ensemble of Gsw(loop) is
      tunable through variation of the Mg(2+) concentration. We quantitatively describe
      the influence of distinct Mg(2+) concentrations on ligand-induced folding
      trajectories both by equilibrium and time-resolved NMR spectroscopy at single
      residue resolution.

PMID- 21890901
TI  - Chromatin disruption in the promoter of bovine leukemia virus during
      transcriptional activation.
AB  - Bovine leukemia virus expression relies on its chromatin organization after
      integration into the host cell genome. Proviral latency, which results from
      transcriptional repression in vivo, represents a viral strategy to escape the
      host immune system and likely allows for tumor progression. Here, we
      discriminated two types of latency: an easily reactivable latent state of the YR2
      provirus and a 'locked' latent state of the L267 provirus. The defective YR2
      provirus was characterized by the presence of nuclease hypersensitive sites at
      the U3/R junction and in the R/U5 region of the 5'-long terminal repeat (5'-LTR),
      whereas the L267 provirus displayed a closed chromatin configuration at the U3/R
      junction. Reactivation of viral expression in YR2 cells by the phorbol 12
      myristate 13-acetate (PMA) plus ionomycin combination was accompanied by a rapid
      but transient chromatin remodeling in the 5'-LTR, leading to an increased PU.1
      and USF-1/USF-2 recruitment in vivo sustained by PMA/ionomycin-mediated USF
      phosphorylation. In contrast, viral expression was not reactivated by
      PMA/ionomycin in L267 cells, because the 5'-LTR U3/R region remained inaccessible
      to nucleases and hypermethylated at CpG dinucleotides. Remarkably, we elucidated
      the BLV 5'-LTR chromatin organization in PBMCs isolated from BLV-infected cows,
      thereby depicting the virus hiding in vivo in its natural host.

PMID- 21890902
TI  - Generating the optimal mRNA for therapy: HPLC purification eliminates immune
      activation and improves translation of nucleoside-modified, protein-encoding
      mRNA.
AB  - In vitro-transcribed mRNA has great therapeutic potential to transiently express
      the encoded protein without the adverse effects of viral and DNA-based
      constructs. Mammalian cells, however, contain RNA sensors of the innate immune
      system that must be considered in the generation of therapeutic RNA.
      Incorporation of modified nucleosides both reduces innate immune activation and
      increases translation of mRNA, but residual induction of type I interferons
      (IFNs) and proinflammatory cytokines remains. We identify that contaminants,
      including double-stranded RNA, in nucleoside-modified in vitro-transcribed RNA
      are responsible for innate immune activation and their removal by high
      performance liquid chromatography (HPLC) results in mRNA that does not induce
      IFNs and inflammatory cytokines and is translated at 10- to 1000-fold greater
      levels in primary cells. Although unmodified mRNAs were translated significantly
      better following purification, they still induced high levels of cytokine
      secretion. HPLC purified nucleoside-modified mRNA is a powerful vector for
      applications ranging from ex vivo stem cell generation to in vivo gene therapy.

PMID- 21890903
TI  - tRNAHis-guanylyltransferase establishes tRNAHis identity.
AB  - Histidine transfer RNA (tRNA) is unique among tRNA species as it carries an
      additional nucleotide at its 5' terminus. This unusual G(-1) residue is the major
      tRNA(His) identity element, and essential for recognition by the cognate histidyl
      tRNA synthetase to allow efficient His-tRNA(His) formation. In many organisms G(
      1) is added post-transcriptionally as part of the tRNA maturation process.
      tRNA(His) guanylyltransferase (Thg1) specifically adds the guanylyate residue by
      recognizing the tRNA(His) anticodon. Thg1 homologs from all three domains of life
      have been the subject of exciting research that gave rise to a detailed
      biochemical, structural and phylogenetic enzyme characterization. Thg1 homologs
      are phylogenetically classified into eukaryal- and archaeal-type enzymes
      differing characteristically in their cofactor requirements and specificity.
      Yeast Thg1 displays a unique but limited ability to add 2-3 G or C residues to
      mutant tRNA substrates, thus catalyzing a 3' -> 5' RNA polymerization. Archaeal
      type Thg1, which has been horizontally transferred to certain bacteria and few
      eukarya, displays a more relaxed substrate range and may play additional roles in
      tRNA editing and repair. The crystal structure of human Thg1 revealed a
      fascinating structural similarity to 5' -> 3' polymerases, indicating that Thg1
      derives from classical polymerases and evolved to assume its specific function in
      tRNA(His) processing.

PMID- 21890904
TI  - A second base pair interaction between U3 small nucleolar RNA and the 5'-ETS
      region is required for early cleavage of the yeast pre-ribosomal RNA.
AB  - In eukaryotes, U3 snoRNA is essential for pre-rRNA maturation. Its 5'-domain was
      found to form base pair interactions with the 18S and 5'-ETS parts of the pre
      rRNA. In Xenopus laevis, two segments of U3 snoRNA form base-pair interactions
      with the 5'-ETS region and only one of them is essential to the maturation
      process. In Saccharomyces cerevisiae, two similar U3 snoRNA-5' ETS interactions
      are possible; but, the functional importance of only one of them had been tested.
      Surprisingly, this interaction, which corresponds to the non-essential one in X.
      laevis, is essential for cell growth and pre-rRNA maturation in yeast. In
      parallel with [Dutca et al. (2011) The initial U3 snoRNA:pre-rRNA base pairing
      interaction required for pre-18S rRNA folding revealed by in vivo chemical
      probing. Nucleic Acids Research, 39, 5164-5180], here we show, that the second
      possible 11-bp long interaction between the 5' domain of S. cerevisiae U3 snoRNA
      and the pre-rRNA 5'-ETS region (helix VI) is also essential for pre-rRNA
      processing and cell growth. Compensatory mutations in one-half of helix VI fully
      restored cell growth. Only a partial restoration of growth was obtained upon
      extension of compensatory mutations to the entire helix VI, suggesting sequence
      requirement for binding of specific proteins. Accordingly, we got strong
      evidences for a role of segment VI in the association of proteins Mpp10, Imp4 and
      Imp3.

PMID- 21890905
TI  - Identification of potentially cytotoxic lesions induced by UVA photoactivation of
      DNA 4-thiothymidine in human cells.
AB  - Photochemotherapy-in which a photosensitizing drug is combined with ultraviolet
      or visible radiation-has proven therapeutic effectiveness. Existing approaches
      have drawbacks, however, and there is a clinical need to develop alternatives
      offering improved target cell selectivity. DNA substitution by 4-thiothymidine
      (S(4)TdR) sensitizes cells to killing by ultraviolet A (UVA) radiation. Here, we
      demonstrate that UVA photoactivation of DNA S(4)TdR does not generate reactive
      oxygen or cause direct DNA breakage and is only minimally mutagenic. In an
      organotypic human skin model, UVA penetration is sufficiently robust to kill
      S(4)TdR-photosensitized epidermal cells. We have investigated the DNA lesions
      responsible for toxicity. Although thymidine is the predominant UVA photoproduct
      of S(4)TdR in dilute solution, more complex lesions are formed when S(4)TdR
      containing oligonucleotides are irradiated. One of these, a thietane/S(5)-(6
      4)T:T, is structurally related to the (6-4) pyrimidine:pyrimidone [(6-4) Py:Py]
      photoproducts induced by UVB/C radiation. These lesions are detectable in DNA
      from S(4)TdR/UVA-treated cells and are excised from DNA more efficiently by
      keratinocytes than by leukaemia cells. UVA irradiation also induces DNA
      interstrand crosslinking of S(4)TdR-containing duplex oligonucleotides. Cells
      defective in repairing (6-4) Py:Py DNA adducts or processing DNA crosslinks are
      extremely sensitive to S(4)TdR/UVA indicating that these lesions contribute
      significantly to S(4)TdR/UVA cytotoxicity.

PMID- 21890907
TI  - Complexity in the binding of minor groove agents: netropsin has two
      thermodynamically different DNA binding modes at a single site.
AB  - Structural results with minor groove binding agents, such as netropsin, have
      provided detailed, atomic level views of DNA molecular recognition. Solution
      studies, however, indicate that there is complexity in the binding of minor
      groove agents to a single site. Netropsin, for example, has two DNA binding
      enthalpies in isothermal titration calorimetry (ITC) experiments that indicate
      the compound simultaneously forms two thermodynamically different complexes at a
      single AATT site. Two proposals for the origin of this unusual observation have
      been developed: (i) two different bound species of netropsin at single binding
      sites and (ii) a netropsin induced DNA hairpin to duplex transition. To develop a
      better understanding of DNA recognition complexity, the two proposals have been
      tested with several DNAs and the methods of mass spectrometry (MS),
      polyacrylamide gel electrophoresis (PAGE) and nuclear magnetic resonance
      spectroscopy in addition to ITC. All of the methods with all of the DNAs
      investigated clearly shows that netropsin forms two different complexes at AATT
      sites, and that the proposal for an induced hairpin to duplex transition in this
      system is incorrect.

PMID- 21890906
TI  - Evolution of the deaminase fold and multiple origins of eukaryotic editing and
      mutagenic nucleic acid deaminases from bacterial toxin systems.
AB  - The deaminase-like fold includes, in addition to nucleic acid/nucleotide
      deaminases, several catalytic domains such as the JAB domain, and others involved
      in nucleotide and ADP-ribose metabolism. Using sensitive sequence and structural
      comparison methods, we develop a comprehensive natural classification of the
      deaminase-like fold and show that its ancestral version was likely to operate on
      nucleotides or nucleic acids. Consequently, we present evidence that a specific
      group of JAB domains are likely to possess a DNA repair function, distinct from
      the previously known deubiquitinating peptidase activity. We also identified
      numerous previously unknown clades of nucleic acid deaminases. Using inference
      based on contextual information, we suggest that most of these clades are toxin
      domains of two distinct classes of bacterial toxin systems, namely polymorphic
      toxins implicated in bacterial interstrain competition and those that target
      distantly related cells. Genome context information suggests that these toxins
      might be delivered via diverse secretory systems, such as Type V, Type VI, PVC
      and a novel PrsW-like intramembrane peptidase-dependent mechanism. We propose
      that certain deaminase toxins might be deployed by diverse extracellular and
      intracellular pathogens as also endosymbionts as effectors targeting nucleic
      acids of host cells. Our analysis suggests that these toxin deaminases have been
      acquired by eukaryotes on several independent occasions and recruited as
      organellar or nucleo-cytoplasmic RNA modifiers, operating on tRNAs, mRNAs and
      short non-coding RNAs, and also as mutators of hyper-variable genes, viruses and
      selfish elements. This scenario potentially explains the origin of mutagenic
      AID/APOBEC-like deaminases, including novel versions from Caenorhabditis,
      Nematostella and diverse algae and a large class of fast-evolving fungal
      deaminases. These observations greatly expand the distribution of possible
      unidentified mutagenic processes catalyzed by nucleic acid deaminases.

PMID- 21890908
TI  - Math fluency is etiologically distinct from untimed math performance, decoding
      fluency, and untimed reading performance: evidence from a twin study.
AB  - The authors examined whether math fluency was independent from untimed math and
      from reading using 314 pairs of school-aged twins drawn from the Western Reserve
      Reading and Math Projects. Twins were assessed through a 90-min home visit at
      approximately age 10 and were reassessed in their homes approximately 1 year
      later. Results suggested that the shared environment and genetics influenced the
      covariance among math fluency, untimed math measures, and reading measures.
      However, roughly two thirds of the variance in math fluency was independent from
      untimed math measures and reading, including reading fluency. The majority of
      this independent variance was the result of genetic factors that were
      longitudinally stable across two measurement occasions. These results suggest
      that math fluency, although related to other math measures, may also be a
      genetically distinct dimension of mathematics performance.

PMID- 21890909
TI  - Distribution of metastatic sites in renal cell carcinoma: a population-based
      analysis.
AB  - BACKGROUND: We assessed the distribution of site-specific metastases in patients
      with renal cell carcinoma (RCC) according to age. Moreover, we evaluated
      recommendations proposed by guidelines and focused specifically on bone and brain
      metastases. PATIENTS AND METHODS: Patients with metastatic RCC (mRCC) were
      abstracted from the Nationwide Inpatient Sample (1998-2007). Age was stratified
      into four groups: <55, 55-64, 65-74 and >= 75 years. Cochran-Armitage trend test
      and multivariable logistic regression analysis tested the relationship between
      age and the rate of multiple metastatic sites. Finally, we examined the rates of
      brain or bone metastases according to the presence of other metastatic sites.
      RESULTS: In 11,157 mRCC patients, the rate of multiple metastatic sites decreased
      with increasing age (P < 0.001). This phenomenon was confirmed in patients with
      lung, bone, liver and brain metastases (all P <= 0.01). The rate of bone
      metastases was 10% in patients with exclusive abdominal metastases and 49% in
      patients with abdominal, thoracic and brain metastases. The rate of brain
      metastases was 2% in patients with exclusive abdominal metastases and 16% in
      patients with thoracic and bone metastases. CONCLUSIONS: The proportion of
      patients with multiple metastatic sites is higher in young patients. The rates of
      bone (10%-49%) and brain (2%-16%) metastases are nonnegligible in mRCC patients.

PMID- 21890910
TI  - Body mass index, abdominal fatness and pancreatic cancer risk: a systematic
      review and non-linear dose-response meta-analysis of prospective studies.
AB  - BACKGROUND: Questions remain about the shape of the dose-response relationship
      between body mass index (BMI) and pancreatic cancer risk, possible confounding by
      smoking, and differences by gender or geographic location. Whether abdominal
      obesity increases risk is unclear. METHODS: We conducted a systematic review and
      meta-analysis of prospective studies of the association between BMI, abdominal
      fatness and pancreatic cancer risk and searched PubMed and several other
      databases up to January 2011. Summary relative risks (RRs) were calculated using
      a random-effects model. RESULTS: Twenty-three prospective studies of BMI and
      pancreatic cancer risk with 9504 cases were included. The summary RR for a 5-unit
      increment was 1.10 [95% confidence interval (CI) 1.07-1.14, I(2) = 19%] and
      results were similar when stratified by gender and geographic location. There was
      evidence of a non-linear association, P(non-linearity) = 0.005; however, among
      nonsmokers, there was increased risk even within the 'normal' BMI range. The
      summary RR for a 10-cm increase in waist circumference was 1.11 (95% CI 1.05
      1.18, I(2) = 0%) and for a 0.1-unit increment in waist-to-hip ratio was 1.19 (95%
      CI 1.09-1.31, I(2) = 11%). CONCLUSIONS: Both general and abdominal fatness
      increases pancreatic cancer risk. Among nonsmokers, risk increases even among
      persons within the normal BMI range.

PMID- 21890911
TI  - Annual Meeting of the American Acadmey of Otolaryngology-Head and Neck Surgery
      Foundation, San Francisco, CA, September 11-14, 2011. Abstracts.

PMID- 21891772
TI  - Serum free p-cresyl sulfate levels predict cardiovascular and all-cause mortality
      in elderly hemodialysis patients--a prospective cohort study.
AB  - BACKGROUND: The mortality rate of elderly hemodialysis (HD) patients is high.
      Serum p-cresyl sulfate (PCS) and indoxyl sulfate (IS) are associated with
      cardiovascular (CV) disease and mortality in renal patients. The association
      between such biomarkers and mortality in elderly HD patients has a high clinical
      value but remains unclear. METHODS: This prospective cohort study investigated
      the association of serum IS and PCS with all-cause and CV mortality in elderly HD
      patients. Multivariate Cox regression analysis was used to estimate the risk of
      all-cause and CV mortality in this prospective cohort. RESULTS: Of 112 patients,
      45 deaths (18 CV deaths) were identified after a mean follow-up of 33.2 months.
      The cumulative and CV survival of patients with lower free PCS was significantly
      better than high free PCS patients. In multivariate Cox regression analysis,
      serum free PCS was associated with all-cause and CV mortality after various
      adjustments, including age, gender and diabetes status (Model 1), albumin (Model
      2), Ca * P product and intact parathyroid hormone (Model 3), hemoglobin and high
      sensitivity C-reactive protein (Model 4) and hierarchically selected covariates
      (age, diabetes status and albumin, Model 5). CONCLUSION: Serum free PCS levels
      may help in predicting risk of all-cause and CV mortality in elderly HD patients
      beyond traditional and uremia related risk factors.

PMID- 21891773
TI  - Effect of the intensity of continuous renal replacement therapy in patients with
      sepsis and acute kidney injury: a single-center randomized clinical trial.
AB  - INTRODUCTION: Acute kidney injury (AKI) is a major complication in patients with
      sepsis and is an independent predictor of mortality. However, the optimal
      intensity of renal replacement therapy for such patients is still controversial.
      METHODS: From 1 January 2004 to 30 September 2009, we randomly assigned 280
      patients with sepsis and AKI to continuous renal replacement therapy by high
      volume hemofiltration (50 mL/kg/h, HVHF) or extra high-volume hemofiltration (85
      mL/kg/h, EHVHF). The primary study outcome was death from any cause within 28, 60
      and 90 days. Results were analyzed by univariate and multivariate methods and by
      Kaplan-Meier survival curves. RESULTS: A total of 141 patients were given EHVHF
      and 139 were given HVHF. The two groups had similar baseline characteristics and
      received treatment for an average of 9.38 days (EHVHF group) and 8.88 days (HVHF
      group). There were no significant differences between the groups in number of
      deaths at 28, 60 or 90 days. There were also no differences between the groups in
      renal outcome of survivors at 90 days. Multivariate analysis indicated that
      inotropic support by norepinephrine, time in hospital of >7 days, blood platelet
      count <8 * 10(9)/L, Acute Physiological and Chronic Health Evaluation (APACHE) II
      score >25, total bilirubin >100 MUmol/L, prothrombin time >18 s, serum creatinine
      <250 MUmol/L and blood urea nitrogen >20 mmol/L were independent risk factors for
      death at 90 days after initiation of renal replacement therapy. CONCLUSIONS: In
      patients with sepsis and AKI, increasing the intensity of renal replacement
      therapy from 50 (HVHF) to 85 mL/kg/h (EHVHF) had no effect on survival at 28 and
      90 days.

PMID- 21891774
TI  - Circulating microRNA expression is reduced in chronic kidney disease.
AB  - BACKGROUND: MicroRNAs (miRNAs) are important regulators of gene expression, which
      have roles in renal development and disease. They exist in biological fluids
      including blood and urine and may have signalling roles and potential as disease
      biomarkers. METHODS: We measured the levels of miRNAs in patients with different
      stages of chronic kidney failure including those receiving maintenance
      haemodialysis treatment. RESULTS: In patients with severe chronic renal failure,
      circulating levels of total and specific miRNAs are reduced in comparison to
      patients with mild renal impairment or normal renal function. A strong
      correlation exists between detected circulating miRNAs and estimated glomerular
      filtration rate, and less strong correlations with other features of chronic
      kidney disease, such as anaemia and hyperparathyroidism. CONCLUSION: These
      findings have important implications for the use of circulating miRNAs as
      biomarkers in individuals with renal impairment and for the pathogenesis of
      uraemia.

PMID- 21891775
TI  - Peritoneal dialysis-associated nontuberculous mycobacterium peritonitis: a
      systematic review of reported cases.
AB  - BACKGROUND: Peritonitis caused by nontuberculous mycobacterium (NTM) is an
      important complication in peritoneal dialysis (PD) patients. METHODS: Cases of PD
      complicated by NTM peritonitis reported in the English language literature were
      identified in the PubMed database. The characteristics of these cases were
      reviewed. RESULTS: In 41 articles, we identified 57 cases of PD-associated NTM
      peritonitis in patients ranging from 5 to 82 years. The prevalent clinical
      findings of these cases were fever, abdominal pain, cloudy fluid and an elevated
      leukocyte count in peritoneal fluid. These findings were non-specific and could
      not be differentiated from symptoms caused by Mycobacterium tuberculosis or other
      bacteria. The majority of these cases received empirical antibacterial therapy
      before diagnosis of NTM peritonitis. Isolates in more than half of the
      peritonitis cases were the rapidly growing Mycobacterium, Mycobacterium fortuitum
      (38.6%) and Mycobacterium chelonae (14.0%). In most cases, PD catheters were
      removed and experience with non-removal was limited. CONCLUSION: Diagnosis of NTM
      infection should be considered in PD patients with peritonitis that are culture
      negative or refractory to empirical antibiotic therapy.

PMID- 21891776
TI  - The retrospective analysis of 343 Czech patients with IgA nephropathy--one centre
      experience.
AB  - BACKGROUND: The aim of our study was to retrospectively analyse the clinical data
      and the histological findings of 343 patients (pts) followed up with IgA
      nephropathy (IgAN) in our department of nephrology. We have assessed the main
      demographic, clinical and histological data, and the medical treatment of IgAN
      pts. METHODS: Multivariate analysis was used to evaluate the effect of different
      variables on >=50% increase of plasma creatinine level from baseline during a
      median follow-up of 4 years. RESULTS: In our group of IgAN pts, the male gender
      (68%) predominated over female gender (32%). At the time of renal biopsy, the
      median age of IgAN pts was 32.3 (18-90) years, the median level of serum
      creatinine was 119 MUmol/L and the median level of proteinuria was 1.8 g/day.
      Most of the pts were found to have arterial hypertension (56.7%). The majority of
      the pts with arterial hypertension were treated with inhibitors of angiotensin
      converting enzyme (80.4%) and the remaining pts (42.6%) were treated with
      angiotensin II receptor blockers. Fifty per cent of the pts (170 pts) were
      treated of corticosteroids, 21% of the pts (71 pts) used a combined
      immunosuppressive treatment of corticosteroids and cyclophosphamide, 8% of the
      pts (27 pts) took azathioprine, 1.5% of the pts (5 pts) took cyclosporine and
      1.5% of the pts (5 pts) were given mycophenolate mofetil. Hypertension at
      presentation, fibrointimal proliferation of arterial vessels, interstitial
      fibrosis and interstitial inflammation were shown to be associated with >=50%
      increase of plasma creatinine level from baseline in univariate analysis (P<0.05
      for hypertension and fibrointimal proliferation; P<0.01 for interstitial fibrosis
      and inflammation). Using stepwise logistic regression presenting proteinuria>2
      g/day [odds ratio (OR)=2.24, P<0.01], tubular atrophy (OR=4.97, P<0.01) and
      damage of tubular epithelium (OR=1.78, P<0.05) were found as risk factors for
      >=50% increase of plasma creatinine level from baseline. CONCLUSION: Our
      retrospective analysis found valuable information not only about the clinical,
      laboratory and histological findings in IgAN pts but also information about the
      risk factors influencing the progression of renal insufficiency.

PMID- 21891777
TI  - Dialysate sodium, serum sodium and mortality in maintenance hemodialysis.
AB  - BACKGROUND: Individuals with end-stage kidney disease appear to have stable pre
      dialysis serum sodium concentrations over time, with lower values associating
      with increased mortality. Dialysate sodium concentrations have increased over
      many years in response to shorter treatments, but the relationship between serum
      sodium, dialysate sodium and outcomes in chronic hemodialysis patients has not
      yet been systematically examined. METHODS: We studied a cohort of 2272
      individuals receiving thrice-weekly hemodialysis treatment. Available data
      included demographics, laboratory and clinical measures, details of the dialysis
      prescription and 30-month follow-up. We examined the distribution of serum and
      dialysate sodium among subjects and compared mortality according to dialysate and
      serum sodium concentrations using Cox regression models. RESULTS: Dialysate
      sodium concentration varied within and among dialysis centers. The pre-dialysis
      serum sodium concentration (mean 136.1 mmol/L) did not differ across dialysate
      sodium concentrations. There was evidence for effect modification for mortality
      according to differing serum sodium and dialysate sodium concentrations (P=0.05).
      For each 4 mmol/L increment in serum sodium, the hazard ratio for death was 0.72
      [95% confidence interval (CI) 0.63-0.81] with lower dialysate sodium compared to
      0.86 (95% CI 0.75-0.99) for higher dialysate sodium. Higher dialysate sodium
      concentration was associated with mortality at higher, but not lower, pre
      dialysis serum sodium concentrations. CONCLUSIONS: The pre-dialysis serum sodium
      concentration appears to be unaffected by the dialysate sodium concentration. The
      relationship between serum and dialysate sodium and mortality appears to be
      variable. Further research is warranted to determine the biological mechanisms of
      these associations and to re-examine total body sodium handling in hemodialysis.

PMID- 21891778
TI  - Participation in a workplace web-based health risk assessment program.
AB  - BACKGROUND: Web-based health risk assessment (HRA) programs can be effective in
      primary prevention of cardiovascular diseases (CVD). Insight into determinants of
      participation could improve implementation in the workplace. AIMS: To evaluate
      determinants of participation and reasons for non-participation in a web-based
      HRA offered to 5125 employees at four Dutch financial and information technology
      services companies. METHODS: The study consisted of a questionnaire to compare
      sex, age, self-rated health, smoking, current work ability and sick leave between
      participants and non-participants in the HRA program, as well as reasons for non
      participation. RESULTS: HRA participation rate was 37% (1907/5125) and 14% of the
      non-participants (423/3102) completed the non-participant questionnaire. There
      were no differences between participants and non-participants in sex, education
      level, smoking, and current work ability. Compared with non-participants,
      participants were older (44 versus 41 years, P < 0.001). Among participants, 85%
      rated their health as 'good' or 'very good', compared with 78% among non
      participants (P < 0.001); 88% of the participants reported fewer than 10 days
      sickness absence in the previous year, compared with 86% of the non-participants
      (P < 0.05). Reported reasons for non-participation included lack of time (39%)
      and not being aware of the opportunity to participate (11%). CONCLUSIONS:
      Evaluation of demographic, health-related, and work-related determinants of
      participation in a web-based HRA showed differences between participants and non
      participants in self-rated health and absenteeism. Implementing a less time
      consuming HRA process and providing adequate information to employees prior to
      inviting them may be necessary to reach larger proportions of employees,
      including those with less favourable health and work characteristics.

PMID- 21891779
TI  - Effect of working conditions on non-work-related sickness absence.
AB  - BACKGROUND: There is limited evidence of the role of working conditions as
      prognostic factors for non-work-related sickness absence (i.e. absence due to
      injuries or diseases of non-occupational origin). AIMS: To analyse the
      association between working conditions and time to return to work (RTW) in
      workers with long-term (>15 days) non-work-related sickness absence. METHODS: We
      followed up a total of 655 workers, who completed a baseline questionnaire
      including physical and psychosocial work factors, until their non-work-related
      long-term sickness absence ended. Time to RTW was determined based on the health
      insurance company register. Cox proportional hazard models were constructed to
      evaluate the associations between working conditions and time to RTW. RESULTS: A
      self-perceived high level of physical activity at work and work with back twisted
      or bent were related to longer duration of sickness absence. We did not find any
      strong evidence of associations between psychosocial work factors and time to
      RTW, although higher job insecurity and low reward showed marginal statistical
      significance. CONCLUSIONS: Hazardous physical working conditions are associated
      with longer duration of non-work-related sickness absence. Workplace ergonomic
      interventions could conceivably shorten the length of sickness absence that has
      not originated at work.

PMID- 21891780
TI  - Work ability, psychosocial hazards and work experience in prison environments.
AB  - BACKGROUND: Work ability is predicted by age- and work-related psychosocial
      hazards; however, its association with work experience has not been studied. Work
      ability has not been studied in prison environments as well. AIMS: To describe
      work ability and its associates among prison workers. METHODS: A cross-sectional
      study was carried out in two prisons in Spain, one large and one medium prison,
      randomly selected from 17 in total. Prison workers were randomly administered a
      voluntary anonymous questionnaire to measure work ability [Work Ability Index
      (WAI)], work-related psychosocial hazards (Spanish version of COPSOQ),
      sociodemographic, lifestyle and work-related variables. RESULTS: Four hundred and
      forty-one workers (54%) participated. Results confirmed that older and more
      experienced workers (analysis of variance analysis) and workers in large prisons
      (t-student) presented significantly lower WAI scores. Quantitative and emotional
      demands, family work conflict, low work control, low autonomy, low social support
      from colleagues and stress had negative significant associations with WAI. Age,
      which highly correlated with work experience (Spearman's r = 0.85), had
      significant association with WAI (beta = -0.62). In the stepwise linear
      regression, the association between age and WAI lost statistical significance
      after controlling for work experience, which maintained significant correlation
      with WAI (beta = -0.37). CONCLUSIONS: The apparent association between age and
      WAI was confounded by work experience. Interventions to improve work ability
      among prison workers may benefit from results of this study to focus their
      efforts on the risk groups in such a psychologically demanding work environment
      rarely examined in previous research.

PMID- 21891781
TI  - Site-specific recombinases: from tag-and-target- to tag-and-exchange-based
      genomic modifications.
AB  - Site-specific recombinases (SSRs) enable novel tag-and-target as well as tag-and
      exchange strategies for tailoring mammalian genomes. If used in combination with
      homologous recombination, which per se is inefficient but can serve to introduce
      SSR sites, the tagged locus lends itself to repeated modification at largely
      increased efficiency and specificity. The more conventional SSR-based genetic
      modifications enable straightforward integration of a transgene with efficiencies
      depending on both the target locus and the vector composition. Only the more
      recent tag-and-exchange strategies in conjunction with advanced selection
      principles enable the clean replacement of a genomically anchored cassette by a
      donor cassette with the related architecture. Meanwhile this recombinase-mediated
      cassette exchange (RMCE) concept could be verified for two classes of SSRs,
      belonging to either the Tyr or the Ser family. Certain members of these open
      different fields of application that will be discussed with reference to the
      molecular properties of the respective enzymes. A major aim of our review is to
      characterize the RMCE-relevant components and describe their optimal utilization
      in the fields of gene therapy and molecular genomics. Early contributions to the
      field of experimental animal models will be mentioned considering in vivo
      modifications enabled by microinjection into oocytes.

PMID- 21891783
TI  - Effect of thinning on anatomical adaptations of Norway spruce needles.
AB  - Conifers and other trees are constantly adapting to changes in light conditions,
      water/nutrient supply and temperatures by physiological and morphological
      modifications of their foliage. However, the relationship between physiological
      processes and anatomical characteristics of foliage has been little explored in
      trees. In this study we evaluated needle structure and function in Norway spruce
      families exposed to different light conditions and transpiration regimes. We
      compared needle characteristics of sun-exposed and shaded current-year needles in
      a control plot and a thinned plot with 50% reduction in stand density. Whole-tree
      transpiration rates remained similar across plots, but increased transpiration of
      lower branches after thinning implies that sun-exposed needles in the thinned
      plot were subjected to higher water stress than sun-exposed needles in the
      control plot. In general, morphological and anatomical needle parameters
      increased with increasing tree height and light intensity. Needle width, needle
      cross-section area, needle stele area and needle flatness (the ratio of needle
      thickness to needle width) differed most between the upper and lower canopy. The
      parameters that were most sensitive to the altered needle water status of the
      upper canopy after thinning were needle thickness, needle flatness and percentage
      of stele area in needle area. These results show that studies comparing needle
      structure or function between tree species should consider not only tree height
      and light gradients, but also needle water status. Unaccounted for differences in
      needle water status may have contributed to the variable relationship between
      needle structure and irradiance that has been observed among conifers.

PMID- 21891784
TI  - Congenital polyarthritis in goat kids attributed to Mycoplasma agalactiae.

PMID- 21891782
TI  - p73 protein regulates DNA damage repair.
AB  - Although the p53 tumor suppressor is relatively well characterized, much less is
      known about the functions of other members of the p53 family, p73 and p63. Here,
      we present evidence that in specific pathological conditions caused by exposure
      of normal cells to bile acids in acidic conditions, p73 protein plays the
      predominant role in the DNA damage response. These pathological conditions
      frequently occur during gastric reflux in the human esophagus and are associated
      with progression to esophageal adenocarcinoma. We found that despite strong DNA
      damage induced by bile acid exposure, only p73 (but not p53 and p63) is
      selectively activated in a c-Abl kinase-dependent manner. The activated p73
      protein induces DNA damage repair. Using a human DNA repair PCR array, we
      identified multiple DNA repair genes affected by p73. Two glycosylases involved
      in base excision repair, SMUG1 and MUTYH, were characterized and found to be
      transcriptionally regulated by p73 in DNA damage conditions. Using a surgical
      procedure in mice, which recapitulates bile acid exposure, we found that p73
      deficiency is associated with increased DNA damage. These findings were further
      investigated with organotypic and traditional cell cultures. Collectively our
      studies demonstrate that p73 plays an important role in the regulation of DNA
      damage repair.

PMID- 21891785
TI  - Large outbreak of blackleg in housed cattle.

PMID- 21891786
TI  - Survey of Salmonella prevalence on commercial turkey breeding and fattening farms
      in the UK in 2006 to 2007.
AB  - A total of 29 breeding turkey holdings and 317 fattening turkey holdings were
      sampled between October 2006 and September 2007 in order to establish the
      baseline prevalence of Salmonella in turkeys in the UK. The weighted holding
      level Salmonella prevalence was found to be 20.1 per cent (95 per cent confidence
      interval [CI] 8.6 to 40.3 per cent) in breeding turkeys and 37.7 per cent (95 per
      cent CI 33.4 to 42.3 per cent) in fattening turkeys. For breeding turkeys, a
      weighted flock-level prevalence, as more than one flock per holding was sampled,
      was estimated at 7.1 per cent (95 per cent CI 3.2 to 14.8 per cent). A total of
      13 different serovars were identified in the survey. The most frequent serovar in
      both turkey flock classes was Salmonella Kottbus, which was found on two breeding
      holdings and 63 of the fattening holdings giving weighted prevalences of 10.4 per
      cent (95 per cent CI 2.6 to 34.1 per cent) and 23.0 per cent (95 per cent CI 19.3
      to 27.3 per cent), respectively. On breeding holdings, a single isolate of
      Salmonella Typhimurium, identified as DT12 (weighted prevalence 3.5 per cent [95
      per cent CI 0.7 to 15.8 per cent] [holding], 0.7 per cent [95 per cent CI 0.1 to
      3.7 per cent] [flock)], was found. On fattening holdings, there were 55 isolates
      of S Typhimurium from 16 holdings, giving a weighted prevalence of this serovar
      of 5.4 per cent (95 per cent CI 3.6 to 8.0 per cent). There were no isolates of
      Salmonella serovars Enteritidis, Hadar, Infantis or Virchow.

PMID- 21891787
TI  - Linked outbreaks and control of porcine reproductive and respiratory syndrome and
      postweaning multisystemic wasting syndrome in a pig farm in Poland.
AB  - In a newly established farrow-to-finish farm (porcine reproductive and
      respiratory virus [PRRSV]-free, porcine circovirus type 2 [PCV-2]-infected),
      reproductive failure was seen seven months after population. The conception rate
      dropped from 89 to 51 per cent, and the abortion rate increased from 0.5 to 11
      per cent. The following month, characteristic lesions of postweaning
      multisystemic wasting syndrome (PMWS) and elevated mortality were observed in
      weaned pigs. Laboratory examinations confirmed reproductive failure due to PRRSV
      and PMWS associated with apparent activation of the PCV-2 circulating in the
      farm. The herd was closed for replacement and a number of measures to improve
      hygiene, environmental conditions and feeding were applied. The abortion rate
      returned to preoutbreak levels four months after the beginning of the PRRS
      outbreak and the conception rate returned to normal four months later. Slower
      improvement was observed regarding the PMWS outbreak, with PMWS-related losses
      disappearing nine months after the detection of PMWS. Analysis of seroconversion
      profiles to PCV-2 and PRRSV during the outbreak and after its control indicated
      that while PRRSV was eliminated from sows and weaners by the control measures,
      the time of PCV-2 infection was unchanged and occurred at seven weeks of age
      during the PMWS outbreak as well as after its elimination. However, the
      elimination of PMWS from the herd coincided with increased levels of maternally
      derived antibodies to PCV-2 in one- to five-week-old pigs and faster serological
      responses to infection with PCV-2.

PMID- 21891788
TI  - Web 2.0 and the veterinary profession: current trends and future implications for
      lifelong learning.
AB  - The NOVICE project is an EU initiative under the Lifelong Learning Programme,
      which aims to develop an online, professional network to promote informal,
      lifelong learning within the veterinary profession, using Web 2.0 tools. To
      inform the development of the network, a need analysis study was undertaken with
      relevant stakeholders. Focus group discussions were undertaken with veterinary
      students and veterinarians and a survey was administered to first-year students
      and recent graduates. The results indicate that use of computers and the internet
      is ubiquitous among junior members of the profession and that use of Web 2.0
      tools is increasing. Concerns raised in relation to participation in online
      communities include verifying the quality of information and issues around
      professionalism. Compared with face-to-face communities, online communities were
      perceived to offer a number of advantages. These include convenient access to
      expert advice on an international scale, as well as helping to alleviate certain
      barriers to participation in formal, continuing education such as time, distance
      and cost.

PMID- 21891789
TI  - Socio-economic inequalities in survival from screen-detected breast cancer in
      South West England: population-based cohort study.
AB  - BACKGROUND: Socio-economic inequalities in breast cancer survival have been
      reported worldwide, but whether these exist in screen detected as well as
      symptomatic women has not been established. Making this distinction will allow
      inferences about the relative contributions of pre- and post-diagnostic delay to
      these inequalities. METHODS: Screening-eligible women diagnosed with breast
      cancer in South West England (2002-06) were followed-up to 2007. Five-year
      relative survival ratios (RSRs) were calculated for each deprivation quintile,
      using deprivation-specific life-tables and a period approach. The 'deprivation
      gap' in survival was calculated as the slope index of inequality between least
      and most deprived women. RESULTS: The study included 11 018 women, of whom 1176
      died during follow-up. Screening status of 54% of women was missing. A clear
      gradient in survival across deprivation groups ranged from 83.6% [95% confidence
      interval (CI) 80.0, 86.6] in the most deprived to 90.8% (95% CI 89.0, 92.3) in
      the least deprived group. Comparing the most deprived to least deprived women,
      the estimated deprivation gap was -9.42% (95% CI -12.80, -6.04, P = 0.003). Among
      screen-detected women, inequalities were attenuated, but persisted, ranging from
      95.6% (95% CI 90.6, 98.0) in the most deprived to 98.2% (95% CI 95.9, 99.2) in
      least deprived; the estimated deprivation gap was -3.03% (95% CI -5.75, -0.85, P
      = 0.023). CONCLUSION: The deprivation gap in survival does not appear as marked
      with screen-detected breast cancer as the other groups, though still apparent.
      Efforts to eliminate inequalities should consider both increasing breast
      screening participation and ensuring equal access through secondary care systems
      for women of lower socio-economic position.

PMID- 21891791
TI  - In-region versus out-of-region hospitalizations at the end of life among older
      rural residents: the relationship between personal and system-related factors.
AB  - BACKGROUND: Even though a large segment of the population lives in rural areas,
      relatively little attention has been paid in the literature to date to hospital
      use at the end of life among rural residents. The objective of this study was to
      examine factors associated with in- or out-of-region hospitalizations at the end
      of life among older rural residents. METHODS: The study included all community
      dwelling adults aged 65 or older living in rural regions of a mid-Western
      Canadian province who had died in fiscal years 2003-04 to 2005-06, as determined
      from Vital Statistics data (N = 5,550). Complete hospital discharge abstract data
      were used to identify in- or out-of-region hospitalizations in the last 6 months
      before death and on the day of death. The type of out-of-region hospitals older
      adults were admitted to was also examined (urban tertiary hospital, urban
      community hospital, and rural hospital). RESULTS: Twenty percent of
      hospitalizations and 21% of hospital deaths occurred in a hospital that was out
      of older adults' region of residence. Compared with decedents aged 65-74, those
      aged 75-84 and even more so those aged 85+ had reduced odds of being hospitalized
      out of region or dying in an out-of-region hospital. Those 85+ years old also had
      reduced odds of being hospitalized in a (out-of-region) tertiary hospital. Higher
      hospital bed rates and physician rates were associated with reduced odds of out
      of-region hospitalization and hospital death. CONCLUSION: Efforts should focus on
      recruiting physicians to those rural areas with low physician rates, as well as
      finding mechanisms to retain physicians in those rural regions.

PMID- 21891790
TI  - Dynamic regulation of glucocorticoid signalling in health and disease.
AB  - Activation of the glucocorticoid receptor (GR) by endogenous and synthetic
      glucocorticoids regulates hundreds of genes to control regulatory networks in
      development, metabolism, cognition and inflammation. Elucidation of the
      mechanisms that regulate glucocorticoid action has highlighted the dynamic nature
      of hormone signalling and provides novel insights into genomic glucocorticoid
      actions. The major factors that regulate GR function include chromatin structure,
      epigenetics, genetic variation and the pattern of glucocorticoid hormone
      secretion. We review our current understanding of the mechanisms that contribute
      to GR signalling and how these contribute to glucocorticoid sensitivity,
      resistance and side effects.

PMID- 21891792
TI  - A rare cause of an ileocaecal mass and lymphadenopathy.

PMID- 21891793
TI  - Further research is required to provide evidence of the effectiveness and
      feasibility of the nurse-led, case management approach to the care of older
      adults with chronic comorbid conditions.

PMID- 21891794
TI  - Nurse-initiated analgesia improves patients' pain experience: time for change?

PMID- 21891795
TI  - Oxygen may reduce dyspnoea in people with COPD who have mild or no hypoxaemia.

PMID- 21891796
TI  - Hydroxycarbamide for very young children with sickle cell anaemia: no effect on
      the primary outcomes of spleen or kidney function, but evidence for decreased
      pain and dactylitis, with minimal toxicity.

PMID- 21891798
TI  - Lung lobectomy in a patient with an implantable left ventricular assist device.
AB  - Non-cardiac surgical procedures in patients with left ventricular assist devices
      (LVADs) pose a special challenge given the hemodynamic and hematologic
      considerations in these patients. During pulmonary procedures in patients with
      LVADs, special attention should be paid to hemodynamics because lung resection
      surgery requires a lateral decubitus position, single-lung ventilation and
      postoperative decrease in the pulmonary vascular bed, all of which may lead to
      inadequate preload to the LVAD. We present a case of lower lobectomy of the left
      lung for an adenocarcinoma found in a patient with an implantable continuous-flow
      LVAD.

PMID- 21891799
TI  - Vascular antispastic medication should take priority over other antihypertensives
      after coronary artery bypass grafting using a radial artery conduit.
AB  - Radial artery conduits have recently been used more often in coronary artery
      bypass grafting because of their potentially better long-term patency than
      saphenous vein conduits. However, vasospasm of the radial artery conduit due to
      its nature as a muscular artery has always been of concern and a variety of
      vasodilators have empirically been used to reduce the risk of spasm. When a
      patient who was preoperatively taking antihypertensive agents undergoes coronary
      artery bypass using a radial artery graft, and if he/she is not hypertensive
      postoperatively, it is not always easy to decide what medication to start with.
      We report a case of a patient with a radial artery graft who did not receive
      vasodilators after surgery due to hypotension. The patient developed vasospasm of
      the radial artery conduit which did not respond to direct injection of
      vasodilators into the conduit but recovered after taking oral vasodilators for
      four weeks.

PMID- 21891797
TI  - HDAC inhibitor SAHA normalizes the levels of VLCFAs in human skin fibroblasts
      from X-ALD patients and downregulates the expression of proinflammatory cytokines
      in Abcd1/2-silenced mouse astrocytes.
AB  - X-adrenoleukodystrophy (X-ALD) is a peroxisomal metabolic disorder caused by
      mutations in the ABCD1 gene encoding the peroxisomal ABC transporter
      adrenoleukodystrophy protein (ALDP). The consistent metabolic abnormality in all
      forms of X-ALD is an inherited defect in the peroxisomal beta-oxidation of very
      long chain FAs (VLCFAs >C22:0) and the resultant pathognomic accumulation of
      VLCFA. The accumulation of VLCFA leads to a neuroinflammatory disease process
      associated with demyelination of the cerebral white matter. The present study
      underlines the importance of a potent histone deacetylase (HDAC) inhibitor,
      suberoylanilide hydroxamic acid (SAHA) in inducing the expression of ABCD2
      [adrenoleukodystrophy-related protein (ALDRP)], and normalizing the peroxisomal
      beta-oxidation, as well as the saturated and monounsaturated VLCFAs in cultured
      human skin fibroblasts of X-ALD patients. The expression of ELOVL1, the single
      elongase catalyzing the synthesis of both saturated VLCFA (C26:0) and
      monounsaturated VLCFA (C26:1), was also reduced by SAHA treatment. In addition,
      using Abcd1/Abcd2-silenced mouse primary astrocytes, we also examined the effects
      of SAHA in VLCFA-induced inflammatory response. SAHA treatment decreased the
      inflammatory response as expression of inducible nitric oxide synthase,
      inflammatory cytokine, and activation of NF-kappaB in Abcd1/Abcd2-silenced mouse
      primary astrocytes was reduced. These observations indicate that SAHA corrects
      both the metabolic disease of VLCFA as well as secondary inflammatory disease;
      therefore, it may be an ideal drug candidate to be tested for X-ALD therapy in
      humans.

PMID- 21891800
TI  - Valve prosthesis-patient mismatch: hemodynamic, echocardiographic and clinical
      consequences.
AB  - OBJECTIVES: The purpose is to evaluate in vivo at rest and under stress
      conditions hemodynamic performance of the small size St. Jude Medical Regent
      (SJMR) prosthetic valve in patients with a body surface area (BSA) of 1.8 +/-
      0.11 m(2) and to define the role of valve prosthesis- patient mismatch on left
      ventricular mass regression following aortic valve replacement. METHODS: We
      evaluated 25 cases (12 males and 13 females, mean age 65.2 +/- 8 years) of aortic
      valve replacement (17 mm SJMR in three cases and 19 mm SJMR in 22 cases). All the
      patients underwent at rest Doppler echocardiography before and after surgery and
      both basal and dobutamine stress echocardiography (DSE) at follow-up. The mean
      duration of follow-up was 41.3 +/- 24 months. RESULTS: A significant reduction in
      mean and peak transaortic gradients and peak transaortic velocity over time
      following valve replacement has been identified. After surgery, there was a
      significant increase of ejection fraction. DSE significantly increased heart
      rate, ejection fraction, peak transaortic gradient and peak transaortic velocity.
      All patients passed DSE without complication. Even if a significant mismatch was
      present in 76% of cases, the left ventricular mass decreased significantly from
      preoperative value of 278.7 +/- 51.1 g to 181.5 +/- 52.73 g, respectively.
      CONCLUSION: Aortic valve replacement with 17 mm SJMR or 19 mm SJMR prostheses
      appear to provide satisfactory clinical and hemodynamic results at rest and under
      DSE, even in those patients with BSA of 1.8 +/- 0.11 m(2) where it was not
      possible to enlarge the aortic annulus. Prosthesis-patient mismatch is not
      associated with lesser regression of left ventricular mass. Dobutamine stress
      echocardiography should be a useful and effective means for evaluating prosthesis
      hemodynamic aspects.

PMID- 21891801
TI  - Surgical treatment of primary intracardiac myxoma: 19 years of experience.
AB  - Cardiac myxoma is the most common benign tumor of the heart. It presents with a
      variety of clinical signs and symptomatology making diagnosis frequently quite a
      challenge. We review our experience with 41 patients who underwent surgical
      intervention for cardiac myxoma between 1994 and 2011. All patients'
      preoperative, intraoperative and postoperative characteristics were recorded.
      They all had a standard sternotomy and cardiopulmonary bypass with cardioplegic
      cardiac arrest and were followed up with clinical examination and
      echocardiography. The surgical goal was to remove not only the tumor but the
      whole area of attachment to prevent recurrence. Biatrial approach facilitated the
      complete excision of the tumor. Surgical excision of cardiac myxoma carries a low
      operative risk and gives excellent short- and long-term results.

PMID- 21891802
TI  - Interatrial rupture of a non-coronary sinus of Valsalva aneurysm: a rare
      presentation of a rare disorder.
AB  - A 65-year-old male was referred to our team after the incidental finding of a
      large non-coronary sinus of Valsalva aneurysm on computed tomography (CT)-scan of
      the thorax. Further imaging with transesophageal echocardiography (TOE) excluded
      intracardiac shunting. Unusually, the aneurysm had ruptured into the interatrial
      septum and was seen to be compressing both atria. At operative intervention, a 20
      mm defect which had replaced the non-coronary sinus was repaired using a patch
      graft. An aneurysm of an aortic sinus is a rare disorder, and a rupture of a non
      coronary sinus typically results in the formation of a fistulous tract in the
      right atrium. These images highlight an unusual case of a non-coronary sinus of
      Valsalva aneurysm which ruptured into the interatrial septum (IAS), and
      demonstrate the benefit of multi-modality cardiac imaging in guiding surgical
      repair.

PMID- 21891803
TI  - Relationship of walking impairment and ankle-brachial index assessments with
      peripheral arterial translesional pressure gradients.
AB  - BACKGROUND: The relationship of peripheral arterial mean translesional pressure
      gradient (TLG) to presenting symptom, functional impairment, and initial
      noninvasive ABI assessments has never been established. OBJECTIVES: To evaluate
      the association between TLG, severity of walking impairment, rest and exercise
      ankle-brachial indices (ABI). METHODS: TLG in 19 patients presenting with
      claudication and single superficial femoral artery lesion were measured
      invasively. TLG was measured at rest and post-hyperemia induction with intra
      arterial adenosine (100 and 200 MUg), nitroglycerin (100 and 200 MUg), and after
      3 minutes of ipsilateral calf cuff pressure inflation-deflation sequence. For
      each patient, a walking impairment questionnaire (WIQ) was completed and rest and
      exercise ABI were measured prior to TLG assessment. RESULTS: Mean age was 60 +/-
      6 years, 89% were men. Mean WIQ score was 4817 +/- 3549, mean rest and exercise
      ABI were 0.79 +/- 0.14 and 0.59 +/- 0.17, respectively, and mean exercise
      duration was 6.3 +/- 3.4 minutes. TLG with 100 MUg of adenosine strongly
      correlates with WIQ score (r = -0.723); rest ABI (r = -0.748); exercise ABI (r = 
      0.888), exercise duration (r = -0.711), and percent angiographic stenosis (r = 
      0.818), respectively (p < 0.01 for all). TLG with adenosine 200 MUg,
      nitroglycerin 100 and 200 MUg and after cuff inflation-deflation also
      demonstrated significant correlation. Receiver operator curve analysis
      demonstrated that a TLG > or = 11 mmHg post 100 MUg adenosine administration had
      71.43% sensitivity and 100% specificity for identifying patients with disease
      defining state of exercise ABI < or = 0.70. CONCLUSION: This study validates the
      utility of invasive TLG measurements using vasodilation for determining the
      functional and hemodynamic significance of superficial femoral artery lesions.

PMID- 21891804
TI  - What is the role of translesional pressure gradient measurement in peripheral
      intervention?

PMID- 21891806
TI  - Conquering CTOs.

PMID- 21891805
TI  - Endoluminal treatment of peripheral chronic total occlusions using the Crosser(r)
      recanalization catheter.
AB  - PURPOSE: Revascularization of lower extremity chronic total occlusions (CTOs) is
      technically challenging. The Crosser(r) recanalization catheter was designed to
      facilitate distal vessel intraluminal entry that is both rapid and safe. We
      present our experience with the Crosser device as primary therapy for peripheral
      CTOs. METHODS: Subjects undergoing evaluation for arterial insufficiency at our
      institution between 2008-2010 who were noted to have a CTO in the lower extremity
      by duplex ultrasonography and who subsequently underwent Crosser recanalization
      were enrolled. Clinical characteristics, ankle-brachial indices, Rutherford
      Becker symptom category, and angiographic CTO parameters were collected. Primary
      technical success was intraluminal delivery of the guidewire into the distal
      vessel solely by the Crosser device. Secondary technical success was assisted
      delivery using the Outback LTD(r) re-entry device. Safety endpoints were the
      occurrence of dissections, thromboembolism, and perforations related to the
      Crosser device. Statistical analysis was performed to find independent predictors
      for failure to achieve Crosser recanalization. RESULTS: Fifty-six subjects with
      73 CTOs were enrolled. The mean Crosser use time was 17.6 +/- 12.7 minutes. The
      overall primary and secondary technical success rates for Crosser recanalization
      were 76.7% and 87.7%, respectively. Technical success was highest for CTOs
      located in the aorto-iliac (90.0%) and tibial (95.2%) arterial segments. There
      were no perforations related to the Crosser device. For successful cases, the
      mean ABI improved significantly from pre- to post-intervention (0.57 +/- 0.13 to
      0.89 +/- 0.15, p < 0.001). The only predictors for failure were lesion length
      longer than 100 mm (p = 0.04) and calcification within 10 mm of the exit cap (p =
      0.02). CONCLUSION: The Crosser device is safe and shows excellent efficacy in
      facilitating guidewire distal lumen entry, especially for aorto-iliac and tibial
      occlusions. The technical success rate for the femoral and popliteal occlusions
      is comparable to those reported with other recanalization techniques.

PMID- 21891807
TI  - New drug-eluting stent implantation for recalcitrant in-stent restenosis treated
      with drug-eluting stents. the Stent-in-Stent Cube (SIS3) registry.
AB  - The best management for patients with recurrent in-stent restenosis is still not
      clear. The aim of the present study was to describe the long-term clinical
      results of re-DES (drug-eluting stent) implantation in patients suffering
      recurrences after stenting with DES for in-BMS (bare metal stent) restenosis.
      METHODS: All consecutive patients with in-BMS restenosis treated with DES and
      presenting with recurrent ISR (in-DES restenosis) treated with re-DES in 3
      tertiary care centers were retrospectively selected and analyzed. RESULTS: In the
      time period 2005-2009, 40 consecutive patients with recalcitrant ISR were
      selected. At a mean follow-up of 701 +/- 570 days, no patient died. The incidence
      of target lesion revascularization (TLR) and target vessel revascularization
      (TVR) was 12.5% and 17.5%, respectively. Survival free from composite endpoint
      (any death + MI + TLR) was 82% at 2 years. CONCLUSIONS: DES implantation for
      patients with recurrent ISR offers good clinical outcomes at long-term follow-up.

PMID- 21891808
TI  - DES "club sandwich": a viable (if imperfect) option for recalcitrant restenosis.

PMID- 21891809
TI  - Initial results of inflammatory response, matrix remodeling, and reactive oxygen
      species following PCI in acute ischemic myocardial injury in man.
AB  - BACKGROUND: Neutrophils and reactive oxygen species (ROS) are suggested to be
      involved in irreversible myocardial reperfusion injury and stunning. We
      investigated the relations between circulating biochemical markers and myocardium
      at risk (MaR), myocardial infarct (MI) size, salvage, and recovery of function in
      man. METHODS AND RESULTS: In patients undergoing PCI serial blood samples were
      acquired for markers of inflammatory response (myeloperoxidase [MPO], neutrophil
      gelatinase-associated lipocalin [NGAL], interleukins 6 and 8 [IL-6/8], tumor
      necrosis factor-a [TNF-a], high-sensitive C-reactive protein [hsCRP]), matrix
      remodeling (matrixmetalloproteinase-9 [MMP-9]) and ROS (malondialdehyde [MDA],
      isoprostane [IsoP]). Samples were obtained before PCI and 1.5, 3, and 24 hours
      after reperfusion. Myocardial perfusion SPECT (MPS) was used to assess MaR. Late
      gadolinum-enhanced cardiac magnetic resonance imaging was performed for regional
      function in the acute setting, at 1 week and 6 months, and at 1 week also for MI
      size. Sixteen patients (15 men; 42-78 years) were enrolled, 12 of whom underwent
      MPS. Peak and cumulative NGAL and cumulative MMP-9 showed inverse correlations to
      MaR. No correlation was found for MI size. Peak MPO correlated inversely to
      salvage and to recovery of regional function in the infarcted segments at 1 week
      and 6 months. CONCLUSIONS: This is the first study in man to show inverse
      relations between circulating NGAL and MMP-9 and MaR. The current results do not
      support that ROS has a role in stunning in man. MI size showed no significant
      correlation to any parameter, challenging inflammatory treatment in reperfusion.

PMID- 21891810
TI  - Transcatheter aortic and mitral valve implantations for failed bioprosthetic
      heart valves.
AB  - BACKGROUND: Restoring degenerated bioprosthetic valves by transcatheter valve
      implantation may obviate the need for redo surgery in carefully selected
      patients. We present our initial experience with valve-in-valve (VIV) procedures
      for failed aortic and mitral bioprosthetic valves. METHODS: Data were collected
      for all patients who underwent VIV procedures at a tertiary medical center (n =
      6). Findings were analyzed and compared with those for transcatheter valve
      implantation in native valves at the same center during the last 3 years (n =
      84). RESULTS: Six patients of mean age 78.3 +/- 13.8 years (range, 51-87)
      underwent VIV procedures with the CoreValve (n = 4) or Edwards-SAPIEN device (n =
      2). Four (66%) had a failed prosthetic aortic valve, and 2 (33%) had a failed
      prosthetic mitral valve. Regurgitation accounted for valve failure in 83.3% of
      the VIV group versus 1.2% of the comparison group (p < 0.001). Procedural success
      and 30-day survival rates were 100%. Patient functional class improved
      significantly from 0% class I/II, 50% class III, and 50% class IV before the
      procedure to 66% class I, 33% class II, and 0% class III/IV after (p < 0.001).
      CONCLUSION: This preliminary experience demonstrates that in carefully selected
      cases, transcathether valve implants can be safely and effectively deployed in
      stenotic and/or regurgitant degenerated bioprosthetic valves. Further evaluations
      in larger series are needed.

PMID- 21891811
TI  - Transradial coronary angiography and percutaneous intervention in the era of
      health care reform, cost containment, and patient-centered care.
AB  - There has been tremendous pressure on cardiovascular services to reduce costs in
      health care delivery while maintaining the quality of care. The transradial
      approach to coronary angiography and interventions has been demonstrated to
      answer this call by offering superior outcomes while reducing the cost burden of
      vascular complications compared to traditional transfemoral approaches. Herein,
      we discuss the cost effectiveness of the transradial approach as a valid modality
      for angiography and interventions in this era of health care reform.

PMID- 21891812
TI  - Modified technique of BMV for severe submitral stenosis.
AB  - We present a case where difficulty was encountered during balloon mitral
      valvotomy (BMV) because of severe submitral stenosis. As the orifice was 0.4 cm2
      at submitral level the BMV balloon catheter could not enter the left ventricle.
      We used a modified technique of liberating the submitral apparatus that
      facilitated successful BMV.

PMID- 21891813
TI  - Management of an unusual type of intra-aortic balloon pump dysfunction.

PMID- 21891814
TI  - Intraventricular stent loss after interventional treatment of a coronary
      dissection--a case report.
AB  - The introduction of stents for treatment of coronary lesions markedly improved
      the outcome of coronary interventions. We report on a female patient who was
      admitted to our hospital with acute coronary syndrome and stent loss into the
      left ventricle during coronary intervention performed in another hospital. Stent
      loss is a very rare but potentially lethal complication of a stent implantation.

PMID- 21891815
TI  - Multimodality imaging to diagnose pulmonary vein stenosis following atrial
      fibrillation ablation.
AB  - BACKGROUND: Atrial fibrillation (AF) is increasing in prevalence. Although
      experienced centers performing radiofrequency pulmonary vein isolation procedures
      have reported success rates approaching 72%, in rare instances it is complicated
      by stenosis of one or more pulmonary veins. In this report we present a case of
      recurrent pulmonary vein stenosis (PVS) following radiofrequency ablation for AF.

PMID- 21891816
TI  - An isolated single L-I type coronary artery with severe LAD lesions treated by
      transradial PCI.
AB  - Cases of coronary arteries with anomalous aortic origin are rare. An isolated
      single coronary artery is a congenital anomaly occurring in approximately 0.024
      0.066% of the population. Atherosclerosis of these arteries is not infrequent
      with potentially severe consequences, but interventional procedures are rarely
      performed. We report an acute coronary syndrome case due to a subtotal paraostial
      left anterior descending (LAD) occlusion of a single L-I type coronary artery.
      Another severe stenosis was also present at mid-LAD. The patient was successfully
      treated with transradial percutaneous coronary intervention (PCI). Our case shows
      that when the anatomy is suitable, complex PCI can be performed successfully in
      single coronary arteries.

PMID- 21891817
TI  - Complete heart block in late presentation of inferior STEMI successfully treated
      with percutaneous coronary intervention.
AB  - A 55-year-old female presented with 4-day history of fatigue and exertional
      shortness of breath. A late presentation inferior ST elevation myocardial
      infarction (STEMI) was diagnosed based on ST elevation in the inferior leads of
      electrocardiography and elevated cardiac troponin T (TnT). She developed complete
      heart block 1 day after admission to the hospital and remained hemodynamically
      stable. She was taken to the catheterization laboratory for a temporary pacing
      wire insertion. Coronary angiogram at the same time showed an occluded right
      coronary artery at the mid-section. The lesion was successfully opened. Within 24
      hours, the patient's heart rhythm returned to sinus with first-degree
      atrioventricular block (AVB), thus avoiding the need for a permanent pacemaker.
      Current guidelines recommend medical management for late presentation
      hemodynamically stable STEMI of more than 72 H onset. Current ACC/AHA/HRS
      Pacemaker Guidelines recommend reperfusion strategy for acute presentation
      inferior STEMI associated with AVB. However, no clear strategy exists in the case
      of late presentation inferior STEMI with advanced AVB. Our case report suggests
      that late coronary intervention could be a management strategy in such a scenario
      in order to avoid a permanent pacemaker.

PMID- 21891818
TI  - Optical coherence tomography findings during "evolving" stent thrombosis.
AB  - Stent thrombosis is a rare but feared complication. While intravascular
      ultrasound and optical coherence tomography are frequently used to unravel
      mechanical predisposing factors in patients suffering from this dreadful
      complication, no information exists on the early pathophysiology of stent
      thrombosis before coronary flow has been interrupted. We present a case where
      optical coherence tomography was used to gain novel insights into the earliest
      stages of stent thrombosis. In our patient with a possible "evolving" stent
      thrombosis, optical coherence tomography revealed a unique "spider web-like" or
      "cheese-like" thrombus morphology not previously reported.

PMID- 21891819
TI  - Desperate times, desperate measures: rotablating dissections in acute myocardial
      infarction.
AB  - The concomitant existence of an acute ST elevation myocardial infarction (STEMI)
      and a truly undilatable lesion is not a common occurrence, although STEMI lesions
      can be calcified and sometimes difficult to fracture. The manufacturer lists the
      presence of a dissection as a contraindication to use for rotational atherectomy.
      There are no previously reported cases in the literature of rotablation of
      significant macro dissections in the setting of acute myocardial infarction (MI).
      Noncompliant balloons, the Cutting Balloon Ultra (Boston Scientific), the Fx
      miniRAILTM (Abbott Vascular), and the "cutting wire" technique have all been
      previously described for calcific lesion modification.1 Heavily calcific lesions
      especially in the setting of a thrombotic infarction may predispose to under
      expansion, restenosis, and stent thrombosis. Rotational atherectomy (RA) through
      plaque ablation and altering arterial wall compliance may be helpful in
      negotiating heavily calcific lesions.2 Previously, a single case report of the
      use of RA in the setting of a STEMI has been reported.3 Two previous RA reports
      have been de- scribed in the setting of acute and delayed healing of dissections;
      however neither were in the setting of acute STEMI.4,5 We describe the first
      report to our knowledge of RA for a truly undilatable lesion with accompanying
      NHLBI type C iatrogenic dissection post balloon dilation during an acute STEMI to
      allow lesion fracture and subsequent stent deployment.

PMID- 21891820
TI  - Smad molecules expression pattern in human bronchial airway induced by sulfur
      mustard.
AB  - Airway remodelling is characterized by the thickening and reorganization of the
      airways seen in mustard lung patients. Mustard lung is the general description
      for the chronic obstructive pulmonary disease induced by sulfur mustard(SM).
      Pulmonary disease was diagnosed as the most important disorder in individuals
      that had been exposed to sulfur mustard. Sulfur mustard is a chemical warfare
      agent developed during Wars. Iraqi forces frequently used it against Iranian
      during Iran -Iraq in the 1980-1988. Peribronchial fibrosis result from airway
      remodeling that include excess of collagen of extracellular matrix deposition in
      the airway wall. Some of Smads families in association with TGF-beta are involved
      in airway remodeling due to lung fibrosis. In the present study we compared the
      mRNA expression of Smad2, Smad3, and Smad4 and Smad7 genes in airway wall
      biopsies of chemical-injured patients with non-injured patients as control. We
      used airway wall biopsies of ten unexposed patients and fifteen SM-induced
      patients. Smads expression was evaluated by RT-PCR followed by bands
      densitometry. Expression levels of Smad3 and Smad4 in SM exposed patients were
      upregulated but Smad2 and Smad7 was not significantly altered. Our results
      revealed that Smad3, and 4 may be involved in airway remodeling process in SM
      induced patients by activation of TGF-beta. Smad pathway is the most represented
      signaling mechanism for airway remodeling and peribronchial fibrosis. The complex
      of Smads in the nucleus affects a series of genes that results in peribronchial
      fibrosis in SM-induced patients.

PMID- 21891821
TI  - FOXP3 gene expression in multiple sclerosis patients pre- and post mesenchymal
      stem cell therapy.
AB  - Multiple Sclerosis (MS) is an inflammatory demyelinating and neurodegenerative
      disorder of the central nervous system (CNS), which mainly affects young adults.
      Activated T lymphocytes promote the neuro-inflammatory cascade of MS by secreting
      pro-inflammatory cytokines and play a significant role in its pathogenesis. T
      lymphocytes may trigger the inflammation, which in turn leads to axonal loss and
      neurodegeneration observed in the course of MS. Currently, there is no cure for
      MS, however, one of the most promising neuroprotective research tools consists of
      the use of bone marrow derived mesenchymal stem cells (MSC). This method promotes
      immune system regulation and possibly induces neurological repair and re
      myelination of the damaged axons. Recent studies have shown that MSC exert an
      immune regulatory function and induce T regulatory-cell proliferation, therefore,
      it may serve as a potentially useful treatment for immune-mediated diseases such
      as MS. In this pilot study a group of MS patients underwent MSC therapy and we
      assayed the expression of an X-linked transcription factor, FoxP3, as a specific
      marker of T Regulatory cells in peripheral blood, prior to and after the
      treatment. Using q RT-PCR for measurement of expression of FoxP3 by peripheral
      blood mononuclear cells, we found that in all subjects, except for one, the
      expression of FoxP3 at 6 months after intrathecal injection of MSC was
      significantly higher than the levels prior to treatment. Such significant
      enhanced expression of FoxP3 associated with clinical stability. Findings from
      this pilot study further support the potential of bone marrow derived MSC for
      treatment of MS patients.

PMID- 21891822
TI  - Spleen and liver dendritic cells differ in their tolerogenic and cytokine
      induction potential.
AB  - Dendritic cells (DCs) play an important role in induction of cellular immune
      responses. It seems that DCs that reside in different organs may be distinct in
      their ability to induce immune responses. This study was done to address the
      differences between spleen and liver DCs in induction of immune response and/or
      tolerance. CD11c+ DCs were separated from the liver and spleen of C57BL/6 mice
      and pulsed with myelin oligodendrocyte glycoprotein (MOG) peptide 35-55. 6105
      MOG35-55 pulsed spleen or liver DCs were injected in foot pad of different groups
      of mice. Control groups received unpulsed DCs. After 5 days, the mononuclear
      cells (MNCs) of the regional lymph nodes were isolated from immunized mice for
      cytokine assays and lymphocyte transformation test. To study the immunologic or
      tolerogenic effects of DCs, three weeks after immunization of mice with MOG
      pulsed liver or spleen DCs, experimental autoimmune encephalomyelitis (EAE) was
      induced in DC-immunized mice by injection of MOG along with complete Freund's
      adjuvant. Our results showed that spleen DCs were more potent in stimulating
      lymph node T cells as illustrated in lymphocyte transformation test. Moreover IL
      10 production was higher in mice immunized with liver DCs compared with those
      immunized with splenic DCs (p=0.017). However, no significant difference in IFN
      gamma production was observed between two groups. We also found that liver
      DCs+MOG immunized mice displayed a significantly delayed disease onset compared
      with spleen DCs+MOG immunized mice and the control groups. The disease score was
      also milder in liver DCs immunized mice compared with other groups. It seems that
      the higher IL-10 production induced by the liver DCs may be one of the main
      factors in down regulation of immune responses in this organ. It can be concluded
      also that the liver DCs may inhibit the progress of EAE by shifting the cytokines
      profile.

PMID- 21891823
TI  - beta-arrestin2 stimulates interleukin-17 production and expression of CD4+ T
      lymphocytes in a murine asthma model.
AB  - Allergic asthma is a complex and chronic inflammatory airway disease. Interleukin
      17 is a pro-inflammatory cytokine which plays critical role in the pathogenesis
      of allergic asthma. It has been reported that beta-arrestin2 regulated the
      development of allergic asthma at a proximal step in the inflammatory cascade. In
      this study, the influence of beta-arrestin2 on Interleukin-17 production and
      expression of CD4+ T lymphocytes in a murine asthma model was investigated.
      Splenic CD4+ T lymphocytes from wild-type mice and those from a murine asthma
      model were purified. CD4+ T lymphocytes from a murine asthma model were
      transfected with siRNAs targeting the beta-arrestin2 or were pretreated with the
      ERK1/2 inhibitor, PD98059. After stimulation, the protein expression of beta
      arrestin2,phosphorylated-ERK1/2 and IL-17 were detection by Western blot; the
      mRNA expression of IL-17 were detected by real-time PCR; the accumulation of IL
      17 in supernatants were detected by ELISA. We found that beta
      arrestin2,phosphorylated-ERK1/2 and IL-17 expression in CD4+ T lymphocytes from a
      murine asthma model were increased compared with those from wild-type mice (p <
      0.01). Treatment of CD4+ T lymphocytes with siRNAs targeting the beta-arrestin2
      down-regulated phosphorylated- ERK 1/2 and IL-17 expression (p < 0.01). PD98059
      decreased IL-17 production and expression in CD4+ T lymphocytes in a murine
      asthma model (p < 0.05). We conclude that beta-arrestin2 stimulated IL-17
      production and expression of CD4+ T lymphocytes in a murine asthma model. The
      effect was partly mediated by ERK 1/2 activation. Targeting beta-arrestin2
      biological activity could be a valid therapeutic approach for the treatment of
      allergic asthma.

PMID- 21891824
TI  - Serotonin in allergic rhinitis: a possible role for behavioural symptoms.
AB  - Allergic rhinitis (AR) is a very frequent disease which is not only characterized
      by nasal symptoms, but also with behavioural changes. This study evaluated the
      serum serotonin levels in patients with pollen-induced AR during and outside the
      pollen season.One-hundred-two (56 females, 46 males, median age: 28.7 years) were
      included in this study: 56 with seasonal AR (SAR) evaluated outside the pollen
      season and so without allergic inflammation and symptoms, and 46 with SAR
      evaluated during the pollen season with symptoms. Blood specimens were collected
      to assess serum concentrations of serotonin and to compare results to scores of a
      Quality of Life (QoL) questionnaire which was performed in all subjects.
      Serotonin serum concentrations were higher in AR patients out of pollen season
      than in (p<0.01). There was a very strong direct relationship between QoL and
      serotonin concentrations.This preliminary study demonstrates that SAR influences
      serotonin concentrations and that serum serotonin could serve as a biomarker in
      AR patients with behavioural symptoms.

PMID- 21891825
TI  - Study of KIR expression and HLA ligands in CD56+ lymphocytes of drug resistant
      tuberculosis patients.
AB  - Analysis of receptor-ligand interactions in the context of diseases necessitates
      to understand how HLA-KIR genotypes function in diseases. Although CD56+
      lymphocytes are derived from multiple lineages, they share a functional
      association with immunosurviellance and antimicrobial responses. The present
      study aimed to determine whether KIR phenotype in CD56 lymphocytes and
      corresponding HLA-class 1 ligands are associated with multidrug resistance
      tuberculosis (MDR-TB). We compared the frequencies of HLA-C and HLA-BW4 genes,
      the expression of KIRs 2DL1/2DS1, 2DL2/2DL3, 3DL1, and 2DS4 and the combinations
      of HLA/KIR in 32 Nifamycin and Isoniazid-resistant TB with those in 68 drug non
      resistant (NR) sputum smear positive pulmonary TB patients. PCR-SSP and flow
      cytometry were performed for HLA and KIRs typing, respectively. We showed no
      significant differences between inhibitory or activating KIRs as well as HLA
      ligands in MDR TB patients compared with NR-TB . The combinations of inhibitory
      KIR-HLA ligands in MDR-TB were much more prevalent, but not statistically
      significant than in NR patients (p=0.07). The frequency of MDR patients with all
      HLA-C and HLA-BW4 ligands was higher than NR-TB (p<0.009). Conversely, the
      percentage of MDR patients having only one kind of HLA gene was significantly
      lower than NR-TB (p<0.01). We conclude that the expression of inhibitory KIRs
      with corresponding HLA ligands genes, and/or co-existence of three HLA class 1
      ligands for inhibitory KIRs may be associated with drug resistance in pulmonary
      tuberculosis.

PMID- 21891826
TI  - Epidemiological study of periocular dermatitis in a specialised hospital
      department.
AB  - Contact dermatitis is frequent skin pathology and eyelids are one of the more
      frequent locations of this pathology. The objective of the present work was to
      study the population distribution of periocular dermatitis, determine the
      allergens which most frequently indicate positive in patch tests and in
      provocative use tests, and analyse the clinical relevance of the positive
      tests.Patients with periocular dermatitis (N=93) underwent a thorough physical
      examination and a patch test with standard series. According to clinical
      suspicions, 76 patients underwent a patch test with specific series. Finally a
      provocative use test was done for 36 patients with suspected products that the
      patients brought. The tests were classified according their relevance.The most
      frequently observed allergen in the patch tests (with standard and specific
      series) was nickel followed by mercury, and anti-glaucoma drops in the
      provocative use tests with patients products.Patients' sex, age, occupation,
      clinical status, presence of associated periocular symptoms, and presence of
      atopic or seborrheic dermatitis and/or rosacea did not relate with relevance.We
      conclude that a clinical diagnosis may not always be made with patch tests with
      standard and specific series due to lack of relevance. It is important to do
      provocative use tests with the products suspected as allergens in those cases
      where patch tests with standard and specific series indicated positive for more
      than one allergen.

PMID- 21891827
TI  - Phosphodiesterases inhibition by Bacilli Calmette-Guerin contributes to decrease
      asthma in allergic rats.
AB  - Phosphodiesterases (PDE) hydrolyse intracellular cAMP and cGMP to inactive 5'
      monophosphates. Decreased level of cAMP is involved in the pathogenesis of
      asthma. We and others have shown that phosphodiesterases were upregulated in the
      lung of allergic rats, and Bacilli Calmette-Guerin (BCG) induced the production
      of cAMP in vitro. However, it is unclear how BCG's effect asthma and whether it
      is related to PDEs.In this study, BCG was intraperitoneally injected into male
      Sprague-Dawley rats sensitized and later the rats were challenged with
      ovabumin/pertusis. The inflammation in lungs was measured. Airway
      hyperresponsiveness was determined using MedLab software after intravenous
      methacholine challenge. Furthermore, cAMP level and adenylate cyclase activity in
      lungs were analyzed by ELISA, phosphodiesterases activities were analyzed by
      HPLC, while PDEs mRNA levels in lungs was analyzed by reverse transcription
      polymerase chain reaction. Administration of BCG significantly attenuated
      allergen-induced lung inflammatory response and hyper responsiveness as compared
      with vehicle treatment. Furthermore, the levels of cAMP in lungs were
      significantly increased in BCG-treated allergic rats. Interestingly,
      administration of BCG decreased the activity of cAMP-PDE, but not adenylyl
      cyclase (AC), activity in lungs of animals. Furthermore, pretreatment with BCG
      significantly decreased the mRNA levels of PDE4A, 4C, 5 and 8, which were induced
      in lungs of allergic rats. BCG administration attenuated airway inflammatory
      response and bronchial hyper responsiveness in rats, which are the most important
      symptoms in asthma. The decreased PDEs mRNA and inhibited cAMP-PDE activities by
      BCG contribute, at least in part, prevention of allergen-induced airway
      inflammation and asthma in rats.

PMID- 21891828
TI  - Alternaria in patients with allergic rhinitis.
AB  - Inhalation of fungal spores is shown to participate in the development of
      allergic rhinitis symptoms. In this study, relation between presence of
      Alternaria in the human nasal cavity and allergic rhinitis is assessed. In a case
      control study, 58 allergic rhinitis patients were compared with a well-matched
      control group of fifty healthy volunteers for sensitization to Alternaria (by
      skin prick test) and detection of Alternaria in their nasal mucous by
      conventional methods (microscopy with Methylene Blue stain and culture in
      Sabourad dextrose agar). Severity of the disease was determined according to the
      ARIA classification. Pearson chi-square test was applied to compare the
      proportional difference between the study groups for detection of Alternaria in
      the nasal cavity, and sensitization to Alternaria. Relation between detection of
      Alternaria and allergic rhinitis was significant [OR = 18.18 (4.02-82.50)] In
      addition, sensitization to Alternaria showed a significant relation with the
      disease [OR = 2.8 (2.1-3.8)]. There was a significant relation between the
      presence of Alternaria in the nasal cavity and sensitization to Alternaria [OR =
      10.4 (3.8-28.3)]. Both sensitization to Alternaria and presence of Alternaria in
      the nasal cavity did not have a significant relation with the severity of
      allergic rhinitis. This study suggests Alternaria as a major allergen that its
      presence in the nasal cavity and subsequent development of sensitization have
      significant role in the induction of allergic rhinitis.

PMID- 21891829
TI  - Two cases of syndromic neutropenia with a report of novel mutation in G6PC3.
AB  - Severe congenital neutropenia (SCN) is a rare primary immunodeficiency. Different
      genes are found to be associated with SCN, including ELA2, HAX1, WAS, GFI1, G
      CSFR. Also, recently G6PC3 as a rare gene in SCN has been reported. Patients with
      G6PC3 often have cardiac and/or urogenital malformations. Two patients with
      persistent severe neutropenia, recurrent infections and maturation arrest at
      promyelocyte-myelocyte stage in their bone marrow were assessed in this study.
      Both patients showed structural heart disease and one of them also showed
      urogenital anomaly. Sequence analyses of G6PC3 in 2 patients revealed two
      different homozygous mutations, one in exon 6 (Asn 313 fs), and the other in exon
      3 (Ser 139 Met), the latter is a new mutation which has not been reported in
      previous studies. It can be concluded that G6PC3 is one of the responsible gene
      for SCN in Iranian patients. Based on the results, a new mutation in G6PC3
      observed in one patient.

PMID- 21891830
TI  - Absence of long-range magnetic ordering in the pyrochlore compound Er2Sn2O7.
AB  - The low temperature behaviour of powder Er2Sn2O7 samples has been studied by
      magnetic susceptibility, heat capacity, and neutron scattering experiments. We
      report here the absence of magnetic ordering down to 100 mK. Anomalies in the
      heat capacity can be accounted for through an analysis of the crystal field
      spectrum observed by inelastic neutron scattering spectroscopy. These new
      measurements on Er2Sn2O7 suggest a new lower bound for the frustration index of f
      = |Theta(CW)|/T(N) = 14/0.1 = 140, placing this compound into a highly frustrated
      regime.

PMID- 21891831
TI  - Zigzag graphene nanoribbons: bandgap and midgap state modulation.
AB  - We study zigzag graphene nanoribbons with periodic edge roughness and report
      significant band gap opening. Interestingly, such nanoribbons have a near-midgap
      state with a small band width. We extensively study the electronic structure and
      the electric-field modulation of the conduction/valence bands and the near-midgap
      state. We summarize the important electronic-structure features like the band
      gap, the band width and the effective mass. We show that by applying an external
      electric field in the width direction, the band width of the near-midgap state
      varies linearly due to the edge localization, whereas the band gap remains almost
      constant. Additionally, the effective mass of these states can switch polarity
      from negative (hole-like) to positive (carrier-like) at the Gamma-point with the
      field modulation.

PMID- 21891832
TI  - Real space observation of current-induced magnetic domain wall displacement in
      Co/Ni nano-wire by photoemission electron microscopy.
AB  - Current-induced magnetic domain wall (DW) displacement in a Co/Ni nano-wire with
      perpendicular magnetic anisotropy was investigated in real space by photoemission
      electron microscopy (PEEM) for the first time. DW velocity determined from the
      PEEM observation was 40 m s(-1) for the current density of 2.5 * 10(12) A m(-2),
      which was consistent with the result obtained by the electrical measurement used
      in our previous reports.

PMID- 21891833
TI  - Adsorption of Cu, Ag, and Au atoms on graphene including van der Waals
      interactions.
AB  - We performed a systematic density functional (DF) study of the adsorption of
      copper, silver, and gold adatoms on pristine graphene, especially accounting for
      van der Waals (vdW) interactions by the vdW-DF and PBE + D2 methods. In
      particular, we analyze the preferred adsorption site (among top, bridge, and
      hollow positions) together with the corresponding distortion of the graphene
      sheet and identify diffusion paths. Both vdW schemes show that the coinage metal
      atoms do bind to the graphene sheet and that in some cases the buckling of the
      graphene layer can be significant. Only the results for silver are qualitatively
      at variance with those obtained with the generalized gradient approximation,
      which gives no binding in this case. However in all three cases, we observe some
      quantitative differences between the vdW-DF and PBE + D2 methods. For instance
      the adsorption energies calculated with the PBE + D2 method are systematically
      higher than the ones obtained with vdW-DF. Moreover, the equilibrium distances
      computed with PBE + D2 are shorter than those calculated with the vdW-DF method.

PMID- 21891834
TI  - Electronic states of a C70 monolayer on the surface of Ag(111).
AB  - We have investigated the electronic states of a C(70) monolayer on the surface of
      Ag(111) (1 ML C(70)/Ag(111)) using synchrotron radiation photoelectron
      spectroscopy and soft x-ray absorption spectroscopy techniques. The experimental
      data exhibit metallic properties and at least 2.6 e(-) charge transfer per C(70)
      molecule. The screening effect of Ag(111) on the electronic structure of C(70) is
      remarkable; it greatly reduces or even eliminates the on-site Hubbard energy. The
      work functions of the C(70) multilayer and monolayer are determined as 4.53 eV
      and 4.52 eV respectively. The energy levels of C(70) align with the Fermi level
      of the Ag(111) substrate, and the shift of the vacuum level caused by C(70)
      adsorption is negligible. Potassium doping indicates that 1 ML C(70)/Ag(111) can
      still accommodate about nine electrons and that the sample remains metallic at
      any doping level.

PMID- 21891835
TI  - Calculating activation energies for temperature compensation in circadian
      rhythms.
AB  - Many biological species possess a circadian clock, which helps them anticipate
      daily variations in the environment. In the absence of external stimuli, the
      rhythm persists autonomously with a period of approximately 24 h. However, single
      pulses of light, nutrients, chemicals or temperature can shift the clock phase.
      In the case of light- and temperature-cycles, this allows entrainment of the
      clock to cycles of exactly 24 h. Circadian clocks have the remarkable property of
      temperature compensation, that is, the period of the circadian rhythm remains
      relatively constant within a physiological range of temperatures. For several
      organisms, temperature-regulated processes within the circadian clock have been
      identified in recent years. However, how these processes contribute to
      temperature compensation is not fully understood. Here, we theoretically
      investigate temperature compensation in general oscillatory systems. It is known
      that every oscillator can be locally temperature compensated around a reference
      temperature, if reactions are appropriately balanced. A balancing is always
      possible if the control coefficient with respect to the oscillation period of at
      least one reaction in the oscillator network is positive. However, for global
      temperature compensation, the whole physiological temperature range is relevant.
      Here, we use an approach which leads to an optimization problem subject to the
      local balancing principle. We use this approach to analyse different circadian
      clock models proposed in the literature and calculate activation energies that
      lead to temperature compensation.

PMID- 21891836
TI  - Skin perfusion pressure measured with a photo sensor in an air-filled plastic
      balloon: validity and reproducibility on the lower leg in normal subjects and
      patients suspected of obliterative arterial disease.
AB  - An inflatable small plastic bag including a photo sensor was constructed for
      measurement of skin perfusion pressure avoiding the rim of the photo sensor over
      bony and tendineous surfaces of the tibia below the knee, at the ankle, and on
      the dorsal forefoot. Compression was obtained using a conical blood pressure cuff
      with continuous decrease from suprasystolic arm pressure. The validity of skin
      perfusion pressure with the new device was compared to that of isotope washout
      below the knee in normal subjects and in patients with an ischemic forefoot with
      acceptable agreement. The method had a high reproducibility within and between
      days in normal subjects. Compared to systolic arterial pressure measured using a
      strain gauge with a cuff on the ankle in normal subjects and patients with
      intermittent claudication the new device showed blood pressure in the skin closer
      to the diastolic pressure. The new pressure device thus had acceptable validity
      and reproducibility for estimation of the skin perfusion pressure and can be used
      on bony and tendineous sites on the lower limb in regions where critical wound
      healing is frequent, e.g. ankle and forefoot.

PMID- 21891837
TI  - Aligned carbon nanotube based ultrasonic microtransducers for durability
      monitoring in civil engineering.
AB  - Structural health monitoring of porous materials such as concrete is becoming a
      major component in our resource-limited economy, as it conditions durable
      exploitation of existing facilities. Durability in porous materials depends on
      nanoscale features which need to be monitored in situ with nanometric resolution.
      To address this problem, we put forward an approach based on the development of a
      new nanosensor, namely a capacitive micrometric ultrasonic transducer whose
      vibrating membrane is made of aligned single-walled carbon nanotubes (SWNT). Such
      sensors are meant to be embedded in large numbers within a porous material in
      order to provide information on its durability by monitoring in situ neighboring
      individual micropores. In the present paper, we report on the feasibility of the
      key building block of the proposed sensor: we have fabricated well-aligned, ultra
      thin, dense SWNT membranes that show above-nanometer amplitudes of vibration over
      a large range of frequencies spanning from 100 kHz to 5 MHz.

PMID- 21891838
TI  - Piezoresistance of top-down suspended Si nanowires.
AB  - Measurements of the gauge factor of suspended, top-down silicon nanowires are
      presented. The nanowires are fabricated with a CMOS compatible process and with
      doping concentrations ranging from 2 * 10(20) down to 5 * 10(17) cm(-3). The
      extracted gauge factors are compared with results on identical non-suspended
      nanowires and with state-of-the-art results. An increase of the gauge factor
      after suspension is demonstrated. For the low doped nanowires a value of 235 is
      measured. Particular attention was paid throughout the experiments to
      distinguishing real resistance change due to strain modulation from resistance
      fluctuations due to charge trapping. Furthermore, a numerical model correlating
      surface charge density with the gauge factor is presented. Comparison of the
      simulations with experimental measurements shows the validity of this approach.
      These results contribute to a deeper understanding of the piezoresistive effect
      in Si nanowires.

PMID- 21891839
TI  - Assembly of live micro-organisms on microstructured PDMS stamps by
      convective/capillary deposition for AFM bio-experiments.
AB  - Immobilization of live micro-organisms on solid substrates is an important
      prerequisite for atomic force microscopy (AFM) bio-experiments. The method
      employed must immobilize the cells firmly enough to enable them to withstand the
      lateral friction forces exerted by the tip during scanning but without denaturing
      the cell interface. In this work, a generic method for the assembly of living
      cells on specific areas of substrates is proposed. It consists in assembling the
      living cells within the patterns of microstructured, functionalized poly
      dimethylsiloxane (PDMS) stamps using convective/capillary deposition. This
      versatile approach is validated by applying it to two systems of foremost
      importance in biotechnology and medicine: Saccharomyces cerevisiae yeasts and
      Aspergillus fumigatus fungal spores. We show that this method allows multiplexing
      AFM nanomechanical measurements by force spectroscopy on S. cerevisiae yeasts and
      high-resolution AFM imaging of germinated Aspergillus conidia in buffer medium.
      These two examples clearly demonstrate the immense potential of micro-organism
      assembly on functionalized, microstructured PDMS stamps by convective/capillary
      deposition for performing rigorous AFM bio-experiments on living cells.

PMID- 21891840
TI  - Spin-polarized quantum pumping in bilayer graphene.
AB  - We study adiabatic quantum pumping in bilayer graphene where two-barrier
      potentials are weakly modulated as pumping parameters. Comparing the results with
      those for a normal quantum pump of non-chiral quasiparticles, we find that the
      chirality of quasiparticles in bilayer graphene heavily affects the pumped
      current through chiral tunnelling. When an exchange splitting induced by the
      proximity of a ferromagnetic insulator is introduced, the pumped current becomes
      spin-polarized. It is interesting that an almost 100% polarized charge current
      and a pure spin current with vanishing charge current can all be achieved under
      suitable conditions. The experimental feasibility and the interlayer asymmetric
      effect in bilayer graphene caused by the gate and the ferromagnet structures are
      also discussed. The results are useful for spintronics applications based on
      graphene.

PMID- 21891841
TI  - SnO2/WO3 core-shell nanorods and their high reversible capacity as lithium-ion
      battery anodes.
AB  - WO(3) nanorods are uniformly coated with SnO(2) nanoparticles via a facile wet
      chemical route. The reversible capacity of SnO(2)/WO(3) core-shell nanorods is
      845.9 mA h g(-1), higher than that of bare WO(3) nanorods, SnO(2) nanostructures,
      and traditional theoretical results. Such behavior can be attributed to a novel
      mechanism by which nanostructured metallic tungsten makes extra Li(2)O (from
      SnO(2)) reversibly convert to Li(+). This mechanism is confirmed by x-ray
      diffraction results. Our results open a way for enhancing the reversible capacity
      of alloy-type metal oxide anode materials.

PMID- 21891842
TI  - Upconversion fluorescent nanoparticles as a potential tool for in-depth imaging.
AB  - Upconversion nanoparticles (UCNs) are nanoparticles that are excited in the near
      infrared (NIR) region with emission in the visible or NIR regions. This makes
      these particles attractive for use in biological imaging as the NIR light can
      penetrate the tissue better with minimal absorption/scattering. This paper
      discusses the study of the depth to which cells can be imaged using these
      nanoparticles. UCNs with NaYF(4) nanocrystals doped with Yb(3+), Er(3+) (visible
      emission)/Yb(3+), Tm(3+) (NIR emission) were synthesized and modified with silica
      enabling their dispersion in water and conjugation of biomolecules to their
      surface. The size of the sample was characterized using transmission electron
      microscopy and the fluorescence measured using a fluorescence spectrometer at an
      excitation of 980 nm. Tissue phantoms were prepared by reported methods to mimic
      skin/muscle tissue and it was observed that the cells could be imaged up to a
      depth of 3 mm using the NIR emitting UCNs. Further, the depth of detection was
      evaluated for UCNs targeted to gap junctions formed between cardiac cells.

PMID- 21891843
TI  - Large-scale ordered silicon microtube arrays fabricated by Poisson spot
      lithography.
AB  - A novel approach based on the Poisson spot effect in a conventional optical
      lithography system is presented for fabricating large-scale ordered ring patterns
      at low cost, in which the pattern geometries are tuned by controlling the
      exposure dose and deliberate design of the mask patterns. Following this by
      cryogenic deep etching, the ring patterns are transferred into Si substrates,
      resulting in various vertical tubular Si array structures. Microscopic analysis
      indicates that the as-fabricated Si microtubes have smooth interior and exterior
      surfaces that are uniform in size, shape and wall-thickness, which exhibit
      potential applications as electronic, biological and medical devices.

PMID- 21891844
TI  - Ultra-fast vapour-liquid-solid synthesis of Si nanowires using ion-beam implanted
      gallium as catalyst.
AB  - The feasibility of gallium as a catalyst for vapour-liquid-solid (VLS) nanowire
      (NW) growth deriving from an implantation process in silicon by a focused ion
      beam (FIB) is investigated. Si(100) substrates are subjected to FIB implantation
      of gallium ions with various ion fluence rates. NW growth is performed in a hot
      wall chemical vapour deposition (CVD) reactor at temperatures between 400 and 500
      degrees C with 2% SiH(4)/He as precursor gas. This process results in ultra-fast
      growth of (112)- and (110)-oriented Si-NWs with a length of several tens of
      micrometres. Further investigation by transmission electron microscopy indicates
      the presence of a NW core-shell structure: while the NW core yields crystalline
      structuring, the shell consists entirely of amorphous material.

PMID- 21891845
TI  - Convenient immobilization of Pt-Sn bimetallic catalysts on nitrogen-doped carbon
      nanotubes for direct alcohol electrocatalytic oxidation.
AB  - Pt-Sn alloy nanoparticles were conveniently immobilized on nitrogen-doped carbon
      nanotubes (NCNTs) through microwave-assisted ethylene glycol reduction. The
      nanoparticles have a narrow particle size distribution with the average particle
      size around 3 nm as measured by transmission electron microscopy and x-ray
      diffraction. The binding energy of metallic Sn passively shifts due to the charge
      transfer from Sn to Pt, as revealed by x-ray photoelectron spectroscopy. In
      comparison with the commercial Pt/C catalyst, Pt/NCNT presents a clear increase
      in activity for alcohol electro-oxidation due to the improved support, while the
      bimetallic Pt-Sn/NCNT has even higher activity owing to the alloying of Pt with
      Sn. Both Pt-Sn/NCNT and Pt/NCNT catalysts exhibit competitive long-term stability
      to Pt/C catalyst. The low cost, simple preparation and superior electrocatalytic
      performance indicate the great potential of Pt-Sn/NCNT in direct alcohol fuel
      cells.

PMID- 21891846
TI  - Purity-enhanced bulk synthesis of thin single-wall carbon nanotubes using iron
      copper catalysts.
AB  - We report high purity and high yield synthesis of single-wall carbon nanotubes
      (SWCNTs) of narrow diameter from iron-copper bimetal catalysts. The SWCNTs with
      diameter of 0.8-1.2 nm are synthesized using the zeolite-supported alcohol
      chemical vapour deposition method. Single metal and bimetal catalysts are
      systematically investigated to achieve both the enhancement of SWCNT yield and
      the suppression of the undesired formation of graphitic impurities. The relative
      yield and purity of SWCNTs are quantified using optical absorption spectroscopy
      with an ultracentrifuge-based purification technique. For the single metal
      catalyst, iron shows the highest catalytic activity compared with the other
      metals such as cobalt, nickel, molybdenum, copper, and platinum. It has been
      found that the addition of copper to iron results in the suppression of
      carbonaceous impurity formation without decreasing the SWCNT yield. The purity
      enhanced SWCNT shows fairly low sheet resistance due to the improvement of inter
      nanotube contacts. This scalable design of SWCNT synthesis with enhanced purity
      is therefore a promising tool for shaping future high performance devices.

PMID- 21891847
TI  - Predictive models for pressure-driven fluid infusions into brain parenchyma.
AB  - Direct infusions into brain parenchyma of biological therapeutics for serious
      brain diseases have been, and are being, considered. However, individual brains,
      as well as distinct cytoarchitectural regions within brains, vary in their
      response to fluid flow and pressure. Further, the tissue responds dynamically to
      these stimuli, requiring a nonlinear treatment of equations that would describe
      fluid flow and drug transport in brain. We here report in detail on an individual
      specific model and a comparison of its prediction with simulations for living
      porcine brains. Two critical features we introduced into our model-absent from
      previous ones, but requirements for any useful simulation-are the infusion
      induced interstitial expansion and the backflow. These are significant
      determinants of the flow. Another feature of our treatment is the use of cross
      property relations to obtain individual-specific parameters that are coefficients
      in the equations. The quantitative results are at least encouraging, showing a
      high fraction of overlap between the computed and measured volumes of
      distribution of a tracer molecule and are potentially clinically useful. Several
      improvements are called for; principally a treatment of the interstitial
      expansion more fundamentally based on poroelasticity and a better delineation of
      the diffusion tensor of a particle confined to the interstitial spaces.

PMID- 21891848
TI  - Beam orientation optimization for intensity modulated radiation therapy using
      adaptive l(2,1)-minimization.
AB  - Beam orientation optimization (BOO) is a key component in the process of
      intensity modulated radiation therapy treatment planning. It determines to what
      degree one can achieve a good treatment plan in the subsequent plan optimization
      process. In this paper, we have developed a BOO algorithm via adaptive l(2, 1)
      minimization. Specifically, we introduce a sparsity objective function term into
      our model which contains weighting factors for each beam angle adaptively
      adjusted during the optimization process. Such an objective function favors a
      small number of beam angles. By optimizing a total objective function consisting
      of a dosimetric term and the sparsity term, we are able to identify unimportant
      beam angles and gradually remove them without largely sacrificing the dosimetric
      objective. In one typical prostate case, the convergence property of our
      algorithm, as well as how beam angles are selected during the optimization
      process, is demonstrated. Fluence map optimization (FMO) is then performed based
      on the optimized beam angles. The resulting plan quality is presented and is
      found to be better than that of equiangular beam orientations. We have further
      systematically validated our algorithm in the contexts of 5-9 coplanar beams for
      five prostate cases and one head and neck case. For each case, the final FMO
      objective function value is used to compare the optimized beam orientations with
      the equiangular ones. It is found that, in the majority of cases tested, our BOO
      algorithm leads to beam configurations which attain lower FMO objective function
      values than those of corresponding equiangular cases, indicating the
      effectiveness of our BOO algorithm. Superior plan qualities are also demonstrated
      by comparing DVH curves between BOO plans and equiangular plans.

PMID- 21891850
TI  - Comment on 'fast attainment of computer cursor control with noninvasively
      acquired brain signals'.
AB  - In a recent paper by Bradberry, Gentili and Contreras-Vidal published in Journal
      of Neural Engineering (2011, 8 036010), an interesting method for the control of
      a two-dimensional mouse cursor was proposed, which apparently attained excellent
      control and good speed with relatively simple techniques. We believe some of the
      results in the paper have been misinterpreted due to a failure in appreciating
      the self-fulfilling nature of the success criteria adopted. In this comment, we
      explain the nature of the problem and attempt to assess its influence on the
      results reported in the aforementioned paper.

PMID- 21891851
TI  - A valley-filtering switch based on strained graphene.
AB  - We investigate valley-dependent transport through a graphene sheet modulated by
      both the substrate strain and the fringe field of two parallel ferromagnetic
      metal (FM) stripes. When the magnetizations of the two FM stripes are switched
      from the parallel to the antiparallel alignment, the total conductance, valley
      polarization and valley conductance excess change greatly over a wide range of
      Fermi energy, which results from the dependence of the valley-related
      transmission suppression on the polarity configuration of inhomogeneous magnetic
      fields. Thus the proposed structure exhibits the significant features of a valley
      filtering switch and a magnetoresistance device.

PMID- 21891852
TI  - The phase diagram for coexisting d-wave superconductivity and charge-density
      waves: cuprates and beyond.
AB  - Phase diagrams of d-wave superconductivity characterized by an order parameter
      Delta coexisting with charge-density waves (CDWs) characterized by an order
      parameter Sigma were constructed for the two-dimensional Fermi surface (FS)
      appropriate to, e.g., cuprates. CDWs were considered as an origin of the
      pseudogap appearing at antinodal FS sections of the d(x2-y2) superconductor. Two
      types of the Sigma-reentrance were found: with the temperature, T, and with the
      opening of the CDW sector, 2alpha. The angular plots in the momentum space for
      the resulting gap profile over the FS ('gap roses') were obtained. The gap
      patterns are rather involved, giving insight into the difficulties of the
      interpretation of photoemission spectra. It was shown that the Sigma-Delta
      coexistence region exists even for the complete dielectric gapping due to the
      distinction between the superconducting and CDW order parameter symmetries. The
      checkerboard and unidirectional CDW configurations were examined, and both the
      phase diagrams and the behavior with T and alpha of the order parameters were
      found to differ. A more general case with a non-zero mismatch angle beta between
      the superconducting lobes and the CDW sectors was analyzed, the case beta = pi/4
      corresponding to the d(xy) symmetry of the superconducting order parameter. The
      phase diagrams were found to be sensitive to beta-variations, showing that
      internal strains and external pressure can drastically affect the behavior of
      Sigma(T) and Delta(T).

PMID- 21891853
TI  - Magnetic properties of hole-doped SCGO, SrCr(8)Ga(4-x)M(x)O(19) (M = Zn, Mg, Cu).
AB  - We report changes in the magnetic properties of hole-doped SCGO, SrCr8Ga4O19,
      induced by replacing non-magnetic Ga3+ with both non-magnetic (Mg2+ and Zn2+) and
      magnetic (Cu2+) cations. The resulting solid solutions, SrCr(8)Ga(4-x)M(x)O(19)
      (M = Zn, Mg, Cu) have been studied by x-ray diffraction and magnetic
      susceptibility measurements. For all cases, at least 10% of Ga can be replaced by
      divalent cations resulting in oxidation of >=5% of the Cr3+ d3 to Cr4+ (d2). The
      hole doping results in an increase in ferromagnetic interactions and reduces the
      magnetic frustration. In the SrCr(8)Ga(4-x)Cu(x)O(19) series an enhancement of
      the spin-glass-like transition is observed, T(f)~ 6 K, which we ascribe to the
      magnetic nature of the Cu2+ (d9) dopant.

PMID- 21891854
TI  - Topological defect motifs in two-dimensional Coulomb clusters.
AB  - We study the distribution of topological defects in two-dimensional Coulomb
      clusters with parabolic lateral confinement. The minima hopping algorithm based
      on molecular dynamics is used to efficiently locate the ground- and low-energy
      metastable states, and their structure is analysed by means of the Delaunay
      triangulation. The size, structure and distribution of geometry-induced lattice
      imperfections strongly depends on the system size and the energetic state.
      Besides isolated disclinations and dislocations, classification of defect motifs
      includes defect compounds-grain boundaries, rosette defects, vacancies and
      interstitial particles. Proliferation of defects in metastable configurations
      destroys the orientational order of the Wigner lattice.

PMID- 21891855
TI  - Structural characterization of self-assembled ZnO nanoparticles obtained by the
      sol-gel method from Zn(CH3COO)2.2H2O.
AB  - Zinc oxide nanopowders were synthesized by the sol-gel method from an ethanol
      solution of zinc acetate dihydrate. Detailed structural and microstructural
      investigations were carried out using x-ray diffraction, Raman spectroscopy,
      thermogravimetric and differential thermal analyses, as well as high-resolution
      transmission electron microscopy (TEM) and field-emission scanning electron
      microscopy. The intermediate compound of the reaction was layered zinc hydroxide
      acetate that further transforms into hexagonally shaped ZnO crystalline
      nanoplates (d(m) = 4 nm), which aggregate into larger spherical particles.
      According to the TEM analysis the ZnO nanoparticles were self-assembled into
      larger particles with the same orientation, i.e. aligned lattice planes of the
      particles. A further solvothermal treatment resulted in hexagonal, prismatic ZnO
      mesocrystals.

PMID- 21891856
TI  - Near-infrared responsive PbS-sensitized photovoltaic photodetectors fabricated by
      the spin-assisted successive ionic layer adsorption and reaction method.
AB  - A PbS-sensitized photovoltaic photodetector responsive to near-infrared (NIR)
      light was fabricated by depositing monolayered PbS nanoparticles on a mesoporous
      TiO(2) (mp-TiO(2)) film via the spin-assisted successive ionic layer adsorption
      and reaction (SILAR) method. By adjusting the size and morphology of the PbS
      nanoparticles through repeated spin-assisted SILAR cycles, the PbS-sensitized
      photovoltaic photodetector achieved an external quantum efficiency of 9.3% at
      1140 nm wavelength and could process signals up to 1 kHz.

PMID- 21891857
TI  - Capacity based nondestructive readout for complementary resistive switches.
AB  - Complementary resistive switches (CRS) were recently suggested to solve the sneak
      path problem of larger passive memory arrays. CRS cells consist of an antiserial
      setup of two bipolar resistive switching cells. The conventional destructive
      readout for CRS cells is based on a current measurement which makes a
      considerable call on the switching endurance. Here, we report a new approach for
      a nondestructive readout (NDRO) based on a capacity measurement. We suggest a
      concept of an alternative setup of a CRS cell in which both resistive switching
      cells have similar switching properties but are distinguishable by different
      capacities. The new approach has the potential of an energy saving and fast
      readout procedure without decreasing cycling performance and is not limited by
      the switching kinetics for integrated passive memory arrays.

PMID- 21891858
TI  - Synergistic manipulation of micro-nanostructures and composition: anatase/rutile
      mixed-phase TiO2 hollow micro-nanospheres with hierarchical mesopores for
      photovoltaic and photocatalytic applications.
AB  - The construction of nanocrystals with controllable composition and desirable
      micro-nanostructures is a well-known challenge. A combination of favorable
      composition and optimized micro-nanostructures can enhance the performance of a
      material significantly. Using TiO(2) as an example, we demonstrate here a facile
      approach to prepare anatase/rutile mixed-phase TiO(2) hollow micro-nanospheres
      with hierarchical mesopores. Our strategy relies on polymer-assisted assembly of
      ~ 5 nm nano-building blocks into three-dimensional hierarchical hollow micro
      nanospheres in a mixed alcohol-water solution. This superior micro-nanostructure
      endows the sample with hierarchical mesopores and a high surface area of 106 m(2)
      g(-1). We also show that, due to the synergetic effects of the mixed-phase
      composition and the micro-nanostructures, the sample exhibited significantly
      improved photovoltaic performance and similar photocatalytic performance compared
      with the commercial Degussa P25. These results suggested that our sample has
      great potential for future photovoltaic and photocatalytic applications.

PMID- 21891859
TI  - A study of Joule heating-induced breakdown of carbon nanotube interconnects.
AB  - We investigate breakdown of carbon nanotube (CNT) interconnects induced by Joule
      heating in air and under high vacuum conditions (10(-5) mbar). A CNT with a
      diameter of 18 nm, which is grown by chemical vapor deposition to connect
      opposing titanium nitride (TiN) electrodes, is able to carry an electrical power
      up to 0.6 mW before breaking down under vacuum, with a corresponding maximum
      current density up to 8 * 10(7) A cm(-2) (compared to 0.16 mW and 2 * 10(7) A cm(
      2) in air). Decoration with electrochemically deposited Ni particles allows
      protection of the CNT interconnect against oxidation and improvement of the heat
      release through the surrounding environment. A CNT decorated with Ni particles is
      able to carry an increased electrical power of about 1.5 mW before breaking down
      under vacuum, with a corresponding maximum current density as high as 1.2 * 10(8)
      A cm(-2). The Joule heating produced along the current carrying CNT interconnect
      is able to melt the Ni particles and promotes the formation of titanium carbon
      nitride which improves the electrical contact between the CNT and the TiN
      electrodes.

PMID- 21891860
TI  - Precise in situ tuning of the critical current of a superconducting nanowire
      using high bias voltage pulses.
AB  - We present a method for in situ tuning of the critical current (or switching
      current) and critical temperature of a superconducting MoGe nanowire using high
      bias voltage pulses. Our main finding is that as the pulse voltage is increased,
      the nanowire demonstrates a reduction, a minimum and then an enhancement of the
      switching current and critical temperature. Using controlled pulsing, the
      switching current of a superconducting nanowire can be set exactly to a desired
      value. These results correlate with in situ transmission electron microscope
      imaging where an initially amorphous nanowire transforms into a single crystal
      nanowire by high bias voltage pulses. We compare our transport measurements to a
      thermally activated model of Little's phase slips in nanowires.

PMID- 21891862
TI  - Identification of polyphenolic compounds and black tea extract as potent
      inhibitors of lipid membrane destabilization by Abeta42 aggregates.
AB  - Amyloid-beta (Abeta) aggregation is a recognized key process in the pathogenesis
      of Alzheimer's disease (AD). Misfolded Abeta peptides self-assemble into higher
      order oligomers that compromise membrane integrity, leading to synaptic
      degeneration and neuronal cell death. The main aim of this study was to explore
      whether small-molecule compounds and black tea extract can protect phospholipid
      membranes from disruption by Abeta aggregates. We first established a robust
      protocol for aggregating Abeta42 peptides into a range of oligomers that
      efficiently permeabilized small unilamellar liposomes. Next, 15 natural plant
      polyphenolic compounds, 8 N'-benzylidene-benzohydrazide (NBB) compounds and black
      tea extract were assessed for their ability to antagonize liposome
      permeabilization by the Abeta42 oligomers. Our data indicates that black tea
      extract, the flavones apigenin and baicalein, and the stilbene
      nordihydroguaiaretic acid (NDGA) are indeed potent inhibitors. Taking into
      consideration the results of all the small-molecule polyphenols and NBB
      compounds, it can be proposed that a dihydroxyphenyl ring structure, alone or as
      part of a flavone scaffold, is particularly effective for protection against
      membrane damage by the Abeta42 oligomers. Given the critical role of membrane
      perforation in the neurodegenerative cascade, these conclusions may guide the
      design and development of novel therapeutic drugs in AD.

PMID- 21891863
TI  - Infant exposure to lead (Pb) and epigenetic modifications in the aging primate
      brain: implications for Alzheimer's disease.
AB  - The beginnings of late onset Alzheimer's disease (LOAD) are still unknown;
      however, the progressive and latent nature of neurodegeneration suggests that the
      triggering event occurs earlier in life. Aging primates exposed to lead (Pb) as
      infants exhibited an overexpression of the amyloid-beta protein precursor
      (AbetaPP), amyloid-beta (Abeta) and enhanced pathologic neurodegeneration. In
      this study, we measured the latent expression of a wide array of brain-specific
      genes and explored whether epigenetic pathways mediated such latent molecular and
      pathological changes. We analyzed the levels of proteins associated with DNA
      methylation, i.e., DNA methyltransferase 1 (Dnmt1), DNA methyltransferase3a
      (Dnmt3a), methyl-CpG binding protein-2 (MeCP2) and those involved in histone
      modifications (acetylated and methylated histones). We monitored the expression
      profiles of these intermediates across the lifespan and analyzed their levels in
      23-year-old primate brains exposed to Pb as infants. Developmental Pb exposure
      altered the gene expression of the arrayed genes, which were predominately
      repressed, with fewer upregulated genes. The latent induction and repression of
      genes was accompanied by a significant decrease in the protein levels of Dnmts,
      MeCP2, and proteins involved in histone modifications. The attenuation of DNA
      methylation enzymes is consistent with hypomethylating effects, which promote
      upregulation of the genes, while the alterations in the histone modifiers are
      associated with the repression of genes. Hence, we deduce that early life
      exposure to Pb can reprogram gene expression resulting in both upregulation and
      down-regulation of genes through alternate epigenetic pathways contributing to an
      enhancement in neurodegeneration in old age.

PMID- 21891864
TI  - N'-benzylidene-benzohydrazides as novel and selective tau-PHF ligands.
AB  - The structure activity relationship of N'-benzylidene-benzohydrazide (NBB)
      binding to tau and paired helical filament (PHF) proteins as well as amyloid
      beta1-42 fibrils indicate differential selectivity for these protein aggregates.
      The ability of the compounds to stain neurofibrillary tangles and senile plaques
      isolated from human AD brain was investigated histochemically. These studies
      resulted in several tau-PHF and amyloid-beta1-42 fibril selective ligands
      respectively. Supported by these results, we rationalized a model for the design
      of selective ligands for tau, PHF, and amyloid-beta1-42 fibrils.

PMID- 21891865
TI  - Cerebrospinal fluid biomarkers in Progranulin mutations carriers.
AB  - Cerebrospinal fluid (CSF) biomarkers (Abeta1-42, total tau, P-181 tau) are
      currently used to support a clinical diagnosis of Alzheimer's disease (AD). The
      CSF profile in frontotemporal lobar degeneration (FTLD) caused by Progranulin
      (GRN) mutation is unknown. We assessed CSF biomarkers in 145 AD, 140 FTLD (20 GRN
      positive, 120 GRN negative) patients, and 38 controls. Taking into account the
      reference values used in clinical practice, GRN mutation carriers and controls
      did not differ significantly for any biomarker, whereas GRN negative FTLD
      patients had higher tau levels than controls (p < 0.001) and patients carrying
      GRN Thr272fs mutation (p = 0.033, Chi-Square test). Comparing CSF biomarkers mean
      values among groups, total tau was significantly increased in GRN negative FTLD
      and in mutation carriers compared with controls (p < 0.001). P-181 tau CSF was
      increased in AD patients and in GRN negative FTLD compared with controls (p <
      0.001), but not in 17 patients carrying the Thr272fs mutation. 88.2% of mutation
      carriers had normal CSF tau, despite the neurodegenerative nature of FTLD. Our
      results suggest that GRN mutation carriers have normal or borderline CSF
      biomarkers. In patients with an AD-like phenotype but normal or borderline CSF
      biomarkers, a diagnosis of FTLD-U caused by GRN mutations should be considered.

PMID- 21891867
TI  - Homocysteine, vitamin B12, and folic acid levels in Alzheimer's disease, mild
      cognitive impairment, and healthy elderly: baseline characteristics in subjects
      of the Australian Imaging Biomarker Lifestyle study.
AB  - There is some debate regarding the differing levels of plasma homocysteine,
      vitamin B12 and serum folate between healthy controls (HC), mild cognitive
      impairment (MCI), and Alzheimer's disease (AD). As part of the Australian Imaging
      Biomarker Lifestyle (AIBL) study of aging cohort, consisting of 1,112
      participants (768 HC, 133 MCI patients, and 211 AD patients), plasma
      homocysteine, vitamin B12, and serum and red cell folate were measured at
      baseline to investigate their levels, their inter-associations, and their
      relationships with cognition. The results of this cross-sectional study showed
      that homocysteine levels were increased in female AD patients compared to female
      HC subjects (+16%, p-value < 0.001), but not in males. Red cell folate, but not
      serum folate, was decreased in AD patients compared to HC (-10%, p-value =
      0.004). Composite z-scores of short- and long-term episodic memory, total
      episodic memory, and global cognition all showed significant negative
      correlations with homocysteine, in all clinical categories. Increasing red cell
      folate had a U-shaped association with homocysteine, so that high red cell folate
      levels were associated with worse long-term episodic memory, total episodic
      memory, and global cognition. These findings underscore the association of plasma
      homocysteine with cognitive deterioration, although not unique to AD, and
      identified an unexpected abnormality of red cell folate.

PMID- 21891868
TI  - Gene signature in Alzheimer's disease and environmental factors: the virus
      chronicle.
AB  - Genome wide association investigations from large cohorts of patients with
      Alzheimer's disease (AD) and non demented controls (CTR) showed that a limited
      set of genes were associated (p > 10-5) with the disease. A very recent study
      from our group showed that an additional limited group of SNP in selected genes
      were associated with AD. In this report we argue that the association of these
      genes with AD is suggestive of a pivotal role of environmental factors in the
      pathogenesis of the disease and one of these factors is virus infection. In other
      words, the genetic signature revealed by genome wide association (GWA) studies
      discloses a network of genes that might influence the ability of the central
      nervous system to cope with and fight against the invasion by virus of the herpes
      family. In fact, Nectin-2 (NC-2); apolipoprotein E (APOE); glycoprotein
      carcinoembryonic antigen related cell adhesion molecule-16 (CEACAM-16); B-cell
      lymphoma-3 (Bcl-3); translocase of outer mitochondrial membrane 40 homolog (T0MM
      40); complement receptor-1 (CR-l); APOJ or clusterin and C-type lectin domain A
      family-16 member (CLEC-16A); Phosphatidyl inositol- binding clathrin assembly
      protein gene (PICALM); ATP-bonding cassette, sub family A, member 7 (ABCA7);
      membrane spanning A4 (MSA4); CD2 associated protein (CD2AP); cluster of
      differentiation 33 (CD33); and ephrin receptor A1 (EPHA1) result in a genetic
      signature that might affect individual brain susceptibility to infection by the
      herpes virus family during aging, leading to neuronal loss, inflammation, and
      amyloid deposition.

PMID- 21891866
TI  - Is TNF a link between aging-related reproductive endocrine dyscrasia and
      Alzheimer's disease?
AB  - This commentary addresses a novel mechanism by which aging-related changes in
      reproductive hormones could mediate their action in the brain. It presents the
      evidence that dyotic endocrine signals modulate the expression of tumor necrosis
      factor (TNF) and related cytokines, and that these cytokines are a functionally
      important downstream link mediating neurodegeneration and dysfunction. This
      convergence of dyotic signaling on TNF-mediated degeneration and dysfunction has
      important implications for understanding the pathophysiology of AD, stroke, and
      traumatic brain disease, and also for the treatment of these diseases.

PMID- 21891869
TI  - From genotype to phenotype: two cases of genetic frontotemporal lobar
      degeneration with premorbid bipolar disorder.
AB  - Frontotemporal lobar degeneration (FTLD) is a common early-onset dementia, which
      shows highly heterogeneous phenotypic presentations. Although an autosomal
      dominant transmission can be found only in about 10% cases, familial aggregation
      is frequently observed in FTLD. Recently, the progranulin gene (GRN) was reported
      to be involved in the disease pathogenesis. We describe two clinically different,
      apparently sporadic FTLD cases, sharing the previously described GRN mutation
      g.11019_11022delCACT (relative to nt1, NCBI NG_007886.1), alias Thr272fs, with a
      premorbid psychiatric history. Both patients are males and were in their sixties
      when diagnosed clinically with, respectively, the behavioral variant of
      frontotemporal dementia (bvFTD) and progressive nonfluent aphasia (PNFA). In both
      cases, the medical history revealed the presence of bipolar spectrum disorders.
      Mutations in GRN are considered to be a major cause of FTLD. However, the
      phenotypes associated with these mutations are highly variable. Our description
      of two novel FTLD genetic cases confirms the high frequency of the
      g.11019_11022delCACT mutation in Northern Italy. On this basis, we recommend to
      consider the presence of this mutation as a possible cause of the disease,
      particularly in patients with premorbid psychiatric symptoms.

PMID- 21891870
TI  - Loss of astrocyte polarization in the tg-ArcSwe mouse model of Alzheimer's
      disease.
AB  - Aquaporin-4 (AQP4) is the predominant water channel in brain and is selectively
      expressed in astrocytes. Astrocytic endfoot membranes exhibit tenfold higher
      densities of AQP4 than non-endfoot membranes, making AQP4 an excellent marker of
      astrocyte polarization. Loss of astrocyte polarization is known to compromise
      astrocytic function and to be associated with impaired water and K+ homeostasis.
      Here we investigate by a combination of light and electron microscopic
      immunocytochemistry whether amyloid deposition is associated with a loss of
      astrocyte polarization, using AQP4 as a marker. We used the tg-ArcSwe mouse model
      of Alzheimer's disease, as this model displays perivascular plaques as well as
      plaques confined to the neuropil. 3D reconstructions were done to establish the
      spatial relation between plaques and astrocytic endfeet, the latter known to
      contain the perivascular pool of AQP4. Changes in AQP4 expression emerge just
      after the appearance of the first plaques. Typically, there is a loss of AQP4
      from endfoot membranes at sites of perivascular amyloid deposits, combined with
      an upregulation of AQP4 in the neuropil surrounding plaques. By electron
      microscopy it could be verified that the upregulation reflects an increased
      concentration of AQP4 in those delicate astrocytic processes that abound in
      synaptic regions. Thus, astrocytes exhibit a redistribution of AQP4 from endfoot
      membranes to non-endfoot membrane domains. The present data suggest that the
      development of amyloid deposits is associated with a loss of astrocyte
      polarization. The possible perturbation of water and K+ homeostasis could
      contribute to cognitive decline and seizure propensity in patients with
      Alzheimer's disease.

PMID- 21891871
TI  - Long-term effects of galantamine on cognitive function in Alzheimer's disease: a
      large-scale international retrospective study.
AB  - In Alzheimer's disease (AD), it is important to consider long-term effects, not
      only in patients receiving treatment, but also in subjects in whom therapy has
      been discontinued. The present analysis evaluates the long-term effects of
      galantamine on cognitive function in AD in terms of Mini-Mental State Examination
      (MMSE) scores for up to 7 years, using both clinical data and epidemiological
      modeling. Consideration is given not only to patients continuing to receive
      galantamine therapy, but also to those who stop this treatment. In a
      retrospective review of medical notes, re-contacted study investigators obtained
      data from 258 patients originally recruited into three previously described
      randomized clinical trials involving galantamine: two placebo-controlled trials
      in mild-to-moderate AD (of 3 and 6 months' duration, followed by open-label
      extensions) and the galantamine-treatment arm of a 12-month comparative study
      with donepezil in moderate AD. Information relating to disease progression was
      collated (up to five MMSE scores, separated by at least 3 months, for each
      patient). Changes in MMSE scores over time were evaluated using observed data. In
      the absence of long-term placebo, the rate of cognitive decline without treatment
      was projected using a previously described epidemiological model. A new,
      exploratory statistical model was also developed. Results showed that patients
      with mild-to-moderate AD who received long-term galantamine treatment exhibited
      attenuated decline in cognitive function, as assessed by MMSE, compared with
      decline predicted in the absence of treatment. Furthermore, patients who stopped
      treatment experienced subsequent cognitive decline at a rate similar to that
      predicted for untreated patients.

PMID- 21891872
TI  - Diffusion-weighted magnetic resonance imaging of the musculoskeletal system: an
      emerging technology with potential to impact clinical decision making.
AB  - Diffusion-weighted imaging (DWI) is an application of magnetic resonance imaging
      that allows the measurement of water movement within and between tissues.
      Originally developed as a way of detecting early signs of stroke or brain
      disease, DWI is now being used to study physiologic events within the
      musculoskeletal system. The accurate measurement of water diffusion can provide
      important information regarding tissue responses associated with trauma and
      disease, as well as offer insight toward the mechanism by which physical therapy
      interventions affect tissues. The purpose of this paper is to discuss the
      rationale for DWI and its potential clinical and research applications for
      patients with musculoskeletal disorders. Specific examples of the use of DWI for
      patients with painful spinal disorders are used as illustrations.

PMID- 21891873
TI  - Screening the lumbopelvic muscles for a relationship to injury of the quadriceps,
      hamstrings, and adductor muscles among elite Australian Football League players.
AB  - STUDY DESIGN: Longitudinal observational study. OBJECTIVES: To examine the
      relationship between severity of preseason hip, groin, and thigh (HGT) muscle
      injuries, and lumbopelvic muscle size, asymmetry, and function at the start and
      end of the preseason. BACKGROUND: In Australian Rules Football, HGT muscle
      injuries have the highest prevalence and incidence. Deficits within the
      lumbopelvic region, such as impaired muscle function and muscle asymmetry, could
      contribute to injuries in the preseason, and injury could, in turn, affect muscle
      size and function. METHODS: MRI examinations were performed on 47 male elite
      Australian Rules Football players at the start and at the end of the football
      preseason. The cross-sectional area (CSA) of multifidus, psoas major, and
      quadratus lumborum muscles was measured, as well as change in trunk CSA due to
      the function of voluntarily contracting the transversus abdominis muscle.
      Injuries occurring during each preseason training session were routinely recorded
      by the club's performance staff. RESULTS: Analysis of variance indicated that
      players with more severe preseason HGT injuries (more training sessions missed)
      had significantly smaller multifidus muscle CSA compared to players with no HGT
      injury (P = .006). No relationship was found for size or asymmetry of the
      quadratus lumborum or psoas major muscles, or ability to contract the transversus
      abdominis muscle through drawing in of the abdominal wall (P>.05). Small
      multifidus muscle size at L5 predicted 5 of 6 players who incurred a more severe
      HGT injury. CONCLUSIONS: An association between multifidus muscle size (relative
      to age, height, and weight) and preseason injury suggests a way to identify
      players at risk of severe HGT injuries. This result needs to be replicated in a
      larger sample before resources are committed to intervention efforts.

PMID- 21891874
TI  - Reliability and diagnostic accuracy of the Lachman test performed in a prone
      position.
AB  - STUDY DESIGN: Prospective, blinded, diagnostic accuracy study. OBJECTIVE: To
      investigate the reliability and diagnostic accuracy of the Lachman test,
      performed in a prone position, to detect the presence of an anterior cruciate
      ligament (ACL) tear. Direct arthroscopic visualization and a consensus of
      clinical findings, including joint arthrometry and magnetic resonance imaging,
      were used as the reference standards. BACKGROUND: An alternative position for
      evaluating the integrity of the ACL has been proposed as a means for examiners
      with smaller hands to adequately stabilize the thigh of a larger individual;
      however, the diagnostic accuracy of this method has not been established.
      METHODS: Fifty-two consecutive patients with a complaint of knee pain were
      independently evaluated in a prone position for the status of their ACL by 2
      physical therapists, before any other diagnostic assessment. The 31 men and 21
      women ranged in age from 16 to 57 (mean +/- SD, 34.3 +/- 4.2) years and in acuity
      of knee injury from 21 to 365 (mean +/- SD, 195 +/- 130) days. RESULTS: Twenty
      three of 52 (44%) of the patients had a torn ACL. The agreement between examiners
      was 90%, with a kappa coefficient of 0.81. The sensitivity of the prone Lachman
      test was 70% and the specificity was 97%, resulting in a positive likelihood
      ratio of 20.17 and a negative likelihood ratio of 0.32. The positive predictive
      value was 94% and the negative predictive value was 80%. The diagnostic odds
      ratio was 64.0, with a number needed to diagnose of 1.5. CONCLUSION: The prone
      Lachman test is a reliable evaluation technique that can be used to confirm the
      presence of an ACL tear; however, the test should not be used as the sole
      criterion to rule out the presence of the injury. LEVEL OF EVIDENCE: Diagnosis,
      level 2b.

PMID- 21891875
TI  - The effect of therapeutic exercise and mobilization on patients with shoulder
      dysfunction : a systematic review with meta-analysis.
AB  - STUDY DESIGN: Systematic review with meta-analysis. OBJECTIVE: To pool and
      summarize the published research evidence examining if the combination of
      therapeutic exercise and joint mobilization is more beneficial than therapeutic
      exercise alone in patients with shoulder dysfunction. BACKGROUND: Therapeutic
      exercise is an effective intervention for patients with shoulder dysfunction,
      which is often supplemented by joint mobilization techniques. Numerous studies
      have examined the effects of the combination of therapeutic exercise and joint
      mobilization on patients with shoulder dysfunction. METHODS: Six databases were
      searched for randomized controlled trials. All the randomized controlled trials
      published in English that have studied the effectiveness of therapeutic exercise
      and joint mobilization on adults with either clinically or radiographically
      confirmed shoulder dysfunction resulting in pain, restriction of range of motion
      (ROM), and/or limitation in function, were included in this review. Effect size
      was calculated in the form of standardized mean difference and 95% confidence
      interval (CI) for each variable, then combined to represent weighted standardized
      mean differences (WSMDs) and 95% CIs. RESULTS: Seven studies that met the
      inclusion criteria were identified, with a total of 290 participants. The WSMDs
      and CIs, which combined the results of all the studies for a particular variable,
      revealed equivocal results for all variables. The resulting WSMD (95% CI) for
      each of the variables was 0.2 (-0.68, 1.08) for pain, 0.15 (-0.67, 0.97) for
      abduction ROM, -0.04 (-0.65, 0.57) for flexion ROM, 0.01(-0.79, 0.81) for
      internal and external rotation ROM, and 0.09 (-0.46, 0.64) for function and
      disability. Even after elimination of sources of heterogeneity, the new WSMDs and
      CIs continued to overlap zero, giving equivocal results. CONCLUSION: The current
      evidence is inconclusive with respect to the beneficial effects of the
      combination of therapeutic exercise and joint mobilization versus therapeutic
      exercise alone for reducing pain, increasing ROM and function, and limiting
      disability in patients with shoulder dysfunction. LEVEL OF EVIDENCE: Therapy,
      level 1a-.

PMID- 21891876
TI  - Evoked spinal reflexes and force development in elite athletes with middle
      portion Achilles tendinopathy.
AB  - STUDY DESIGN: Controlled laboratory study. OBJECTIVES: To compare the
      neuromuscular function of the triceps surae muscle bilaterally in elite athletes
      with unilateral chronic Achilles tendinopathy. BACKGROUND: Previous studies
      suggest that tendinopathies or chronic pain may lead to a spinal/supraspinal
      level modulation of the excitability or voluntary activation of ipsilateral motor
      units. However, this has not been studied in Achilles tendinopathy. METHODS:
      Fourteen college athletes (mean +/- SD age, 24.2 +/- 1.7 years) who had
      unilateral chronic middle-portion tendinopathy in their Achilles tendons were
      recruited. Bilateral measurements of soleus reflex tests, including H-reflex and
      V wave, and rate of force development (RFD), as well as corresponding
      electromyography of the tibialis anterior and triceps surae muscles, were
      performed. Statistical within-subject and between-leg comparisons were made.
      RESULTS: In the leg with tendinopathy, the V wave of the soleus muscle was
      significantly increased (P<.001). The side with tendinopathy also had a reduced
      normalized RFD (0-30, 0-50, and 0-100 ms) in plantar flexion, and concomitant
      higher electromyography ratios between the tibialis anterior and soleus (0-30 and
      0-50 milliseconds) during the early stage of explosive contractions (P<.05). No
      significant differences were found for H-reflex, maximal plantar flexion and
      dorsiflexion torque, and absolute RFD. CONCLUSIONS: Higher volitional supraspinal
      reflexes and lower maximal-strength independent force development occur in the
      triceps surae of elite athletes with unilateral middle-portion Achilles
      tendinopathy. These changes potentially indicate an acquired compensatory
      mechanism for maximal force production and deficits in explosive strength. The
      RFD is also suggested as a sensitive parameter to depict neuromuscular changes
      during treatment of chronic tendinopathies.

PMID- 21891877
TI  - Muscle functional MRI as an imaging tool to evaluate muscle activity.
AB  - Muscle functional magnetic resonance imaging (mfMRI) is an innovative technique
      that offers a noninvasive method to quantify changes in muscle physiology
      following the performance of exercise. The mfMRI technique is based on signal
      intensity changes due to increases in the relaxation time of tissue water. In
      contemporary practice, mfMRI has proven to be an excellent tool for assessing the
      extent of muscle activation following the performance of a task and for the
      evaluation of neuromuscular adaptations as a result of therapeutic interventions.
      This article focuses on the underlying mechanisms and methods of mfMRI, discusses
      the validity and advantages of the method, and provides an overview of studies in
      which mfMRI is used to evaluate the effect of exercise and exercise training on
      muscle activity in both experimental and clinical studies.

PMID- 21891878
TI  - Meniscus repair and transplantation: a comprehensive update.
AB  - Preservation of meniscal tissue is paramount for long-term joint function,
      especially in younger patients who are athletically active. Many studies have
      reported encouraging results following repair of meniscus tears for both simple
      longitudinal tears located in the periphery and complex multiplanar tears that
      extend into the central third avascular region. This operation is usually
      indicated in active patients who have tibiofemoral joint line pain and are less
      than 50 years of age. However, not all meniscus tears are repairable, especially
      if considerable damage has occurred. In select patients, meniscus transplantation
      may restore partial load-bearing meniscus function, decrease symptoms, and
      provide chondroprotective effects. The initial postoperative goal after both
      meniscus repair and transplantation is to prevent excessive weight bearing, as
      high compressive and shear forces can disrupt healing meniscus repair sites and
      transplants. Immediate knee motion and muscle strengthening are initiated the day
      after surgery. Variations are built into the rehabilitation protocol according to
      the type, location, and size of the meniscus repair, if concomitant procedures
      are performed, and if articular cartilage damage is present. Meniscus repairs
      located in the periphery heal rapidly, whereas complex multiplanar repairs tend
      to heal more slowly and require greater caution. The authors have reported the
      efficacy of the rehabilitation programs and the results of meniscus repair and
      transplantation in many studies.

PMID- 21891879
TI  - Treatment of patients with degenerative cervical radiculopathy using a multimodal
      conservative approach in a geriatric population: a case series.
AB  - STUDY DESIGN: Retrospective clinical case series. OBJECTIVE: To describe the
      management of 10 patients with advanced cervical spondyloarthrosis with
      radiculopathy, using manual therapy, intermittent mechanical cervical traction,
      and home exercises. BACKGROUND: Predictors and short-term outcomes of cervical
      radiculopathy have been published. These predictors have not been developed for,
      or applied to, geriatric patients with spondylitic radiculopathy. CASE
      DESCRIPTION: A series of 10 patients (aged 67 to 82 years) were referred to a
      physical therapist for medically prediagnosed cervical spondyloarthrosis and
      radiculopathy, as determined by magnetic resonance imaging. Neck Disability Index
      (NDI), numeric pain rating scale (NPRS), upper limb tension testing, Spurling's
      test, and the cervical distraction test were all completed on each patient at
      initial examination and at discharge. NDI and NPRS data were also collected at 6
      months posttreatment. Intervention included manual therapy (including high
      velocity low-amplitude thrust manipulation) of the upper thoracic and cervical
      spine, intermittent mechanical cervical traction, and a home program (including
      deep cervical flexor strengthening) for 6 to 12 sessions over a period of 3 to 6
      weeks. OUTCOMES: All 10 patients had substantial improvement in NPRS and NDI
      scores. The mean NPRS score was less than 1/10, and the mean NDI score was 6/50
      at discharge, compared to the original mean NPRS and NDI scores of 5.7 and 27.4,
      respectively. All patients reported maintaining those gains for 6 months.
      DISCUSSION: A multimodal approach for patients diagnosed with cervical
      spondyloarthrosis with radicular symptoms was useful in this geriatric population
      to reduce pain, minimize radicular symptoms, and improve functional outcomes.
      LEVEL OF EVIDENCE: Therapy, level 4.

PMID- 21891880
TI  - Management of anterior cruciate ligament injuries in skeletally immature
      individuals.
AB  - Anterior cruciate ligament (ACL) injuries in skeletally immature individuals
      remain a challenge for the child, the parents, orthopaedic surgeons, and physical
      therapists. The main challenges are the potential risk of recurrent instability,
      secondary injuries following nonoperative treatment, and the risks involved with
      surgical treatment due to the vulnerability of the epiphyseal growth plates. We
      first present the physiological background for considerations that must be made
      when advising on treatment alternatives for skeletally immature individuals after
      ACL injury. The implications of continuous musculoskeletal development for
      treatment decisions are emphasized. No randomized controlled trials have been
      performed to investigate outcomes of different treatment algorithms. There is no
      consensus in the literature on clinical treatment decision criteria for whether a
      skeletally immature child should undergo transphyseal ACL reconstruction, physeal
      sparing ACL reconstruction, or nonoperative treatment. Additionally, well
      described rehabilitation programs designed for either nonoperative treatment or
      postoperative rehabilitation have not been published. Based on the currently
      available evidence, we propose a treatment algorithm for the management of ACL
      injuries in skeletally immature individuals. Finally, we suggest directions for
      future prospective studies, which should include development of valid and
      reliable outcome measures and specific rehabilitation programs.

PMID- 21891882
TI  - Using teledentistry for providing the specialist access to rural Indians.

PMID- 21891881
TI  - Change in knee cartilage volume in individuals completing a therapeutic exercise
      program for knee osteoarthritis.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVES: To characterize knee
      cartilage change in individuals with knee osteoarthritis (KOA) who have completed
      a therapeutic exercise program. BACKGROUND: While therapeutic exercise is
      frequently used successfully to improve pain and function in individuals with
      KOA, no studies have reported the volume of cartilage change or individual
      factors that may impact volume of cartilage change in those completing an
      exercise program for KOA. METHODS: Thirteen individuals with KOA underwent
      magnetic resonance imaging to quantify cartilage volume change in the weight
      bearing regions of the medial and lateral femoral condyles and the entire surface
      of the tibial plateaus from baseline to 1-year follow-up. Body structure and
      function measures were taken for body mass index, knee axis alignment, knee
      motion, and knee strength. Activity limitations and activity levels were also
      measured prior to the therapeutic exercise program, using the Western Ontario and
      McMaster Universities Osteoarthritis Index and the Physical Activity Scale for
      the Elderly. At 6 months from baseline, follow-up clinical measurements of knee
      strength and motion were performed. At 1 year from baseline, imaging of the knee
      cartilage and knee alignment were performed, and participants completed the
      Western Ontario and McMaster Universities Osteoarthritis Index and Physical
      Activity Scale for the Elderly. RESULTS: The central region of the medial femoral
      condyle (cMF) had a median volume of cartilage loss of 3.8%. The other 3 knee
      tibiofemoral articular surfaces had minimal median cartilage volume change.
      Individuals were dichotomized into progressors (n = 6) and nonprogressors (n =
      7), based on the standard error of measurement of cartilage volume change for the
      cMF. Progressors were younger, had a larger body mass index, had a higher
      Kellgren-Lawrence grade in the medial compartment of the knee, and had a greater
      increase in knee varus alignment from baseline to 1-year follow-up. The
      progressors also had frontal plane hip and knee kinetics during baseline gait
      analysis that potentially increased medial knee joint loading. CONCLUSION: The
      loss of cMF cartilage volume was highly variable and the median loss of cartilage
      was within the range previously reported. Seven of the 13 individuals did not
      have cMF cartilage volume loss greater than the standard error of measurement.
      Change in cartilage volume of the cMF may be influenced to a greater extent by
      personal factors than by completion of a therapeutic exercise program. Additional
      research is needed to decipher the interactions among therapeutic exercise and
      personal characteristics that impact knee cartilage loss.

PMID- 21891883
TI  - Effect of ProRoot MTA, Portland cement, and amalgam on the expression of
      fibronectin, collagen I, and TGFbeta by human periodontal ligament fibroblasts in
      vitro.
AB  - CONTEXT: Today many materials have been introduced for root-end filling
      materials. One of them is mineral trioxide aggregate (MTA) that is mentioned as a
      gold standard. AIMS: The purpose of this in vitro study was to evaluate the
      reaction of human periodontal ligament fibroblasts to the root-end filling
      materials, such as ProRoot MTA, Portland cement, and amalgam. SETTINGS AND
      DESIGN: Eight impacted teeth were extracted in aseptic condition. The tissues
      around the roots were used to obtain fibroblast cells. After cell proliferation,
      they were cultured in the chamber slides and the extracts of the materials were
      added to the wells. MATERIALS AND METHODS: Immunocytochemical method for
      measuring the expression of Fibronectin, collagen I and transforming growth
      factor beta (TGF(r)) was performed by Olysia Bioreport Imaging Software.
      STATISTICAL ANALYSIS USED: The results were analyzed by SPSS 13.0 and Tukey post
      hoc test with P<0.05 as the limit of significance. RESULTS: Collagen expression
      in MTA specimens was higher than the other groups in 24 h significantly. After 48
      h, the Portland cement group showed the most expression of collagen significantly
      and after 1 week, Portland cement and MTA groups had the most expression of
      collagen but there was no significant difference between these 2 groups. After 1
      week, the Portland cement group demonstrated a higher amount of TGF(r) and
      fibronectin. CONCLUSIONS: The results suggest that Portland cement can be used as
      a less expensive root filling material with low toxicity. It has better effects
      than amalgam on the fibroblasts.

PMID- 21891884
TI  - Self-reported tobacco use, knowledge on tobacco legislation and tobacco hazards
      among adolescents in rural Kerala State.
AB  - CONTEXT: Tobacco consumption initiated during the adolescent period is a major
      contributor to the pathogenesis of fatal diseases in adulthood. Information on
      tobacco use and awareness regarding tobacco legislation and hazards among
      adolescents in rural Kerala is limited. AIMS: To assess the prevalence of tobacco
      use among adolescent students in a rural district in Kerala state and to
      understand the extent of awareness about the prominent legislative measures
      against tobacco and tobacco hazards. MATERIALS AND METHODS: Data on awareness
      regarding health hazards due to tobacco use and legislation against tobacco
      consumption were collected from students of 15 randomly selected high schools in
      an educational sub-district in Kerala, using a cross-sectional study design. Chi
      square and Fisher's exact test statistics were used for statistical analysis.
      RESULTS: A total of 1473 students participated in the study, of which 79% were
      males (mean age 15.4 years, SD 1.5). The overall prevalence of 'current tobacco
      users' was 8%. A significant association between age and tobacco use was noted
      among tobacco habitues (P<0.05). Awareness regarding legislation against smoking
      in public places was more in the higher age-groups (P<0.05). Females were more
      aware of the 'smoking ban' than males (P<0.05). Our survey of the awareness
      regarding the hazards associated with tobacco use revealed that 41.5% of the
      students knew about the link between oral cancer and tobacco, with the awareness
      being greater among females than among males (64.3% vs 35.4%). CONCLUSION: The
      finding that tobacco consumption increases with age is a matter of concern. In
      addition to their clinical work, dental professionals should also educate the
      public on the hazards of tobacco and conduct tobacco cessation programmes for
      adolescent groups to control the tobacco epidemic.

PMID- 21891885
TI  - Comparison of the linear dimensional accuracy of denture bases cured the by
      conventional method and by the new press technique.
AB  - AIM: The purpose of this study was to investigate and compare the linear
      dimensional accuracy of denture bases processed with the conventional heat
      polymerization technique and the Rafael and Saide (RS) tension system, taking a
      multidirectional approach. MATERIALS AND METHODS: Twenty standard edentulous
      maxillary casts were randomly assigned into two groups. A uniform denture base of
      1.5 mm thickness was fabricated in wax and later processed by two methods: Group
      I acrylic resin flasked with the conventional technique and Group II acrylic
      resin flasked with the RS tension system. The dimensional accuracy was assessed
      using traveling microscope. RESULTS: The linear dimensional changes that occurred
      between the dentures produced with the new press method and the conventional
      method were statistically insignificant and ranged from 0.002 to 0.11. The
      dimensionally stable areas were the canines and the most unstable was the
      posterior palate. CONCLUSIONS: The results of this study suggest that the maximum
      linear dimensional change occurs around the molars and palatal segment, with the
      most stable areas being the canines. There was no significant linear dimensional
      change of the dentures processed between the conventional and the new press
      technique.

PMID- 21891886
TI  - In vitro evaluation of marginal leakage using invasive and noninvasive technique
      of light cure glass ionomer and flowable polyacid modified composite resin used
      as pit and fissure sealant.
AB  - AIM: This study compared the microleakage of light cure glass ionomer and
      flowable compomer as pit and fissure sealant, with and without tooth preparation.
      MATERIALS AND METHODS: One hundred premolars that were extracted for orthodontic
      purpose were used. After adequate storage and surface debridement, the teeth were
      randomly divided into four groups. In Group I and III, the occlusal surfaces were
      left intact, while in Group II and Group IV, tooth surfaces were prepared. Teeth
      in Group I and Group II were sealed with Light cure glass ionomer, whereas
      flowable compomer was used to seal teeth in Group III and IV. The sealed teeth
      were then immersed in dye. Subsequently, buccolingual sections were made and each
      section was examined under stereomicroscope for microleakage followed by scoring.
      RESULTS: In group I, microleakage score ranged from 2 to 4 with mean of 3.64 (+/
      0.757), while in group II the range was observed to be 1-4 with mean of 2.88 (+/
      1.236). Group III recorded a range of 0-4 with the mean of 2.20 (+/-1.443) while
      0-2 and 0.60 (+/-0.707) being the range and mean observed, respectively, for
      group IV. CONCLUSION: Flowable compomer placed after tooth preparation showed
      better penetration and less marginal leakage than the light cure glass ionomer.

PMID- 21891887
TI  - The effect of bur preparation on the surface roughness and reline bond strength
      of urethane dimethacrylate denture base resin.
AB  - BACKGROUND: The clinical success of relining depends on the ability of reline
      resin to bond to denture base. Surface preparations may influence reline bond
      strength of urethane-based dimethacrylate denture base resin. AIM: To investigate
      the effect of bur preparation on the surface roughness (R a ) of eclipse denture
      base resin and its shear bond strength (SBS) to an intra-oral self-curing reline
      material. The mode of reline bonding failure was also examined. MATERIALS AND
      METHODS: Twenty-four cylindrical EclipseTM specimens were prepared and separated
      into three groups of eight specimens each. Two groups were subjected to
      mechanical preparation using standard and fine tungsten carbide (TC) burs and the
      third group (control) was left unprepared. The R a of all specimens was measured
      using a contact stylus profilometer. Subsequently, relining was done on the
      prepared surface and SBS testing was carried out a day later using a universal
      testing machine. RESULTS: One-way ANOVA revealed significant differences (P<0.05)
      in R a and SBS values for all the groups. Post-hoc Tukey's HSD test showed
      significant differences (P<0.05) between all the groups in the R a values. For
      SBS also there were significant differences (P<0.05), except between standard bur
      and control. CONCLUSIONS: 1) There was a statistically significant difference in
      the R a of EclipseTM specimens prepared using different carbide burs (P<0.05). 2)
      There was a statistically significant difference in the relined SBS (P<0.05) when
      prepared using different burs, but the difference between the standard bur and
      the control group was not statistically significant.

PMID- 21891888
TI  - Palmistry: a tool for dental caries prediction!
AB  - BACKGROUND: Dermatoglyphics can prove to be an extremely useful tool for
      preliminary investigations in conditions with a suspected genetic base. Since
      caries is a multifactorial disease with the influence of genetic pattern, early
      prediction for high-risk children can help in using effective and efficient
      caries preventive measures that are a part of the pedodontist arsenal. AIMS AND
      OBJECTIVES: This study was done to determine the genetic aspect involved in the
      occurrence of dental caries through a cost-effective means, which can be used in
      field studies. MATERIALS AND METHODS: 550 kindergarten school children in the age
      group 3-6 years were examined during a school examination camp. Of these, only
      336 children were included in the study. They were divided into four groups as
      follows: caries-free males (df score=0), caries-free females, caries males (df
      score>=10), caries females. The handprints of each child were taken and the
      frequency of occurrence of type of dermatoglyphic pattern on fingertip of each
      digit was noted. Separate df scores were recorded. SPSS software and test of
      proportions were used for the analysis. RESULTS AND CONCLUSION: Handprints of
      caries-free children, especially females, showed maximum ulnar loops. The caries
      group showed maximum occurrence of whorls (r=2:1), which were more prevalent in
      females on the left hand 3rd digit than in males where the whorls were found on
      the right hand 3 rd digit, and also low total ridge count, especially in males.

PMID- 21891889
TI  - A comparative evaluation of film and digital panoramic radiographs in the
      assessment of position and morphology of impacted mandibular third molars.
AB  - BACKGROUND AND OBJECTIVE: Digital photo stimulable phosphor (PSP)-based
      radiography has many known theoretical advantages over conventional film
      radiography but its diagnostic efficacy has to be assessed clinically. This study
      compared the efficiency of conventional film-based panoramic radiographs with
      that of digital PSP-based panoramic radiographs in the assessment of position and
      morphology of impacted mandibular third molars. MATERIALS AND METHODS: We
      selected a total of 80 impacted mandibular third molars that fulfilled the
      inclusion and exclusion criteria of this study. Both conventional film-based
      panoramic radiographs and digital PSP-based panoramic radiographs were taken of
      all the study samples and the teeth were later surgically removed. Conventional
      film-based and digital PSP-based panoramic radiographs were compared for their
      relative efficiencies in the assessment of impaction status, position of tooth,
      number of roots, root morphology, and proximity to mandibular canal of impacted
      mandibular third molars. An oral surgeon graded these same factors during/after
      surgical exploration and this assessment was considered the gold standard. The
      data obtained were statistically analyzed using descriptive statistics, chi
      square test, and McNemar's test. RESULTS: There was no statistically significant
      difference between conventional film-based radiographic assessment and digital
      PSP-based panoramic radiographic assessment of impaction status, position of
      tooth, number of roots, and proximity to mandibular canal of impacted mandibular
      third molars (P>0.05). However, there was significant difference between the two
      methods with regard to assessment of root morphology of impacted mandibular third
      molars (P=0.00). INTERPRETATION AND CONCLUSION: Conventional film-based panoramic
      radiographs and digital PSP-based panoramic radiographs were comparable in their
      accuracy in the preoperative study of impacted mandibular third molar with regard
      to impaction status, tooth position, number of roots, and proximity to the
      mandibular canal. Digital PSP-based panoramic radiographs were more accurate than
      conventional film-based panoramic radiographs in the assessment of root
      morphology of impacted mandibular third molars. Hence, we conclude that digital
      PSP-based panoramic radiographs can be used as an effective alternative to
      conventional film-based panoramic radiographs for assessment of position and
      morphology of impacted mandibular third molars.

PMID- 21891890
TI  - Evaluation of the relative efficacy of an alloplast used alone and in conjunction
      with an osteoclast inhibitor in the treatment of human periodontal infrabony
      defects: a clinical and radiological study.
AB  - BACKGROUND: Mucoperiosteal flap surgery stimulates varying amounts of alveolar
      bone loss due to accelerated osteoclastic activity [Regional Accelerated
      Phenomenon (RAP)]. Alendronate sodium inhibits osteoclastic activity and is
      thought to result in a net increase in osteoblastic activity. We undertook a
      preliminary study evaluating the effect of adjunctive use of topically delivered
      bisphosphonate alendronate (ALN) along with regenerative bone graft material in
      the treatment of periodontal infrabony defects. MATERIALS AND METHODS: Fifteen
      patients with two-walled or three-walled infrabony defects were selected. In each
      patient, the infrabony defect of one side of arch was designated as group A
      (control site) and received hydroxyapatite (HA) bone graft material, while the
      infrabony defect on the contralateral side of same arch was designated as group B
      (test site) and received HA+200 MUg drug solution of ALN. RESULTS: Both the
      groups exhibited a highly significant reduction in probing depth and gain in
      clinical attachment level and linear bone fill at the end of 24 weeks.
      Comparative evaluation between the study groups revealed a statistically
      nonsignificant reduction in probing depth (P=0.128NS) and mean gain in attachment
      level (P=0.218NS). However, there was a statistically significant gain in linear
      bone fill (P=0.040*) in group B as compared to group A. CONCLUSIONS: The results
      suggest that use of ALN along with graft material led to enhanced linear bone
      fill at the surgical site. This research provides a clue that bone-targeting
      properties of bisphosphonates can be harnessed along with regenerative materials
      to potentiate osseous regeneration.

PMID- 21891891
TI  - Lingual vascular canal assessment by dental computed tomography: a retrospective
      study.
AB  - BACKGROUND: Lingual vascular canal (LVC) is an important anatomical structure in
      mandibular anterior region. Trauma to this structure during implant placement has
      been reported in this study. Dental computed tomography (DCT) provides a three
      dimensional visualization of lingual vascular canal. AIM: To assess the
      frequency, location, and size of LVC using dental CT. MATERIALS AND METHODS: A
      retrospective analysis of 75 mandibular DCT was done. Evaluation was done to
      detect the frequency, size, and number of lingual vascular canal using Seimens
      Somatom Sensation 64. RESULTS: About 73.3% patients (male=34, female=21)
      demonstrated presence of LVC with only one patient showing two canals. The mean
      distance from the inferior border of mandible was 0.5 mm, S.D.+/-0.70. The mean
      diameter of the canal was 0.31 mm, S.D.+/-0.70. CONCLUSION: Dental CT provides
      adequate information regarding frequency, number, and size of lingual vascular
      canal, which is an important anatomical structure in mandibular anterior region.

PMID- 21891892
TI  - Evaluation of an innovative radiographic technique--parallel profile radiography-
      to determine the dimensions of dentogingival unit.
AB  - BACKGROUND: Maintenance of gingival health is a key factor for longevity of the
      teeth as well as of restorations. The physiologic dentogingival unit (DGU), which
      is composed of the epithelial and connective tissue attachments of the gingiva,
      functions as a barrier against microbial entry into the periodontium. Invasion of
      this space triggers inflammation and causes periodontal destruction. Despite the
      clinical relevance of the determination of the length and width of the DGU, there
      is no standardized technique. The length of the DGU can be either determined by
      histologic preparations or by transgingival probing. Although width can also be
      assessed by transgingival probing or with an ultrasound device, they are either
      invasive or expensive AIMS: This study sought to evaluate an innovative
      radiographic exploration technique--parallel profile radiography--for measuring
      the dimensions of the DGU on the labial surfaces of anterior teeth. MATERIALS AND
      METHODS: Two radiographs were made using the long-cone parallel technique in ten
      individuals, one in frontal projection, while the second radiograph was a
      parallel profile radiograph obtained from a lateral position. The length and
      width of the DGU was measured using computer software. Transgingival probing
      (trans-sulcular) was done for these same patients and length of the DGU was
      measured. The values obtained by the two methods were compared. Pearson product
      correlation coefficient was calculated to examine the agreement between the
      values obtained by PPRx and transgingival probing. RESULTS: The mean biologic
      width by the parallel profile radiography (PPRx) technique was 1.72 mm (range
      0.94-2.11 mm), while the mean thickness of the gingiva was 1.38 mm (range 0.92
      1.77 mm). The mean biologic width by trans-gingival probing was 1.6 mm (range 0.8
      2.2 mm). Pearson product correlation coefficient (r) for the above values was
      0.914; thus, a high degree of agreement exists between the PPRx and TGP
      techniques. CONCLUSIONS: We conclude that the biologic width of the DGU in humans
      can be measured with the PPRx technique. The values obtained agree with the
      values obtained by transgingival probing, a technique considered standard so far.
      Thus, the PPRx technique offers a simple, concise, noninvasive, and reproducible
      method that can be used in the clinical setup to measure both the length and
      thickness of the DGU with accuracy.

PMID- 21891893
TI  - Perception differences of altered dental esthetics by dental professionals and
      laypersons.
AB  - BACKGROUND: When we smile, our smile could often become the target of close
      scrutiny by the person you are smiling at. A trained eye readily detects any
      asymmetricity or any aspect of that smile which may be out of balance, or
      disharmonious with its environment. The purpose of this study was to determine
      whether any such asymmetric or symmetric dental discrepancies were detectable by
      various groups of evaluators. AIMS: The aim was to determine whether asymmetric
      and symmetric anterior dental discrepancies were detectable by orthodontists,
      general dentists, and laypersons, and to establish threshold levels for several
      specific aesthetic criteria that could be used by orthodontists and general
      dentists as an aid in the treatment planning. MATERIALS AND METHODS: Three images
      of smiles were intentionally altered with a software-imaging program. The
      alterations involved the crown length, crown width, midline diastema, and the
      papillary height of the maxillary anterior teeth. These altered images were then
      rated by groups of general dentists, orthodontists, and laypersons using a visual
      analog scale. Statistical analysis of their responses resulted in the
      establishment of threshold levels of attractiveness for each group. RESULTS: The
      orthodontists were more critical than the general dentists and laypersons when
      evaluating asymmetric crown length discrepancies. All three groups could identify
      a unilateral crown width discrepancy of 2.0 mm. A small midline diastema was not
      rated as unattractive by any group. Reduction of papillary height was generally
      rated as less attractive. CONCLUSIONS: Asymmetric alterations make teeth more
      unattractive not only to the dental professionals, but also to laypersons.

PMID- 21891894
TI  - Assessment of periodontal status among dental fluorosis subjects using community
      periodontal index of treatment needs.
AB  - AIM: To determine the periodontal status and treatment needs among dental
      fluorosis subjects residing in Ennore, Chennai, using Community Periodontal Index
      of Treatment Needs (CPITN). MATERIALS AND METHODS: All the subjects with dental
      fluorosis above 15 years of age, permanent residents of Ennore, were included in
      the study. Subjects with known systemic diseases and subjects with other
      intrinsic dental stains were excluded from the study. Periodontal status was
      estimated using CPITN and Dental fluorosis was recorded using Dean's Dental
      Fluorosis Index. RESULTS: The total number of study subjects was 1075, of which
      489 were males and 586 were females. Males were predominantly affected with
      periodontal disease than females. This was found to be statistically significant
      (P=0.000). The association between Degree of Fluorosis and Periodontal Status is
      statistically significant (P=0.000). There was statistically significant
      difference in mean number of sextants between the degree of fluorosis in each of
      the periodontal status (P=0.000). CONCLUSION: The finding that the lower
      prevalence of shallow pockets in the study area, where the fluoride level in the
      drinking water ranges from 1.83 to 2.01 ppm, indicates that the use of fluoride
      in water is beneficial to the periodontal tissues.

PMID- 21891895
TI  - Microleakage of bonded amalgam restorations using different adhesive agents with
      dye under vacuum: an in vitro study.
AB  - AIM: In an effort to minimize tooth preparation, yet provide additional retention
      to compromised tooth structure, bonded amalgam restorations were introduced.
      Various resin-based adhesives have been tried earlier under bonded amalgam
      restorations. Still there are controversies regarding the outcome of bonded
      amalgam restorations regarding their adaptability to the tooth structure and
      microleakage. Therefore, this study was undertaken to compare the microleakage of
      bonded amalgam restorations using different adhesive materials. MATERIALS AND
      METHODS: Standard Class I cavities were prepared on occlusal surfaces of 60 human
      molars. Teeth (n=60) were divided into three groups according to the material
      employed, as follows: group I: amalgam with glass ionomer cement (GIC) (type I);
      group II: amalgam with resin cement (Panavia F 2.0) and group III: amalgam with
      Copalex varnish as a control. Following restoration, the teeth were submitted to
      thermal cycling. The teeth were subsequently immersed in 2% rhodamine B dye under
      vacuum for 48 hours and sectioned to allow the assessment of microleakage under
      stereomicroscope. RESULTS: The values were tabulated and the results were
      statistically analyzed using analysis of variance (ANOVA), Tukey's post hoc test
      and Kruskal-Wallis test. Amalgam with type I GIC showed the least leakage with no
      statistically significant difference (P value 0.226) when compared to amalgam
      with Panavia F 2.0 and amalgam with varnish (P value 0.107). CONCLUSION: It can
      be concluded that bonded amalgam with type I GIC is a good alternative to amalgam
      with resin cement (Panavia F 2.0) and amalgam with varnish for large
      restorations, with the added advantages of GICs. CLINICAL SIGNIFICANCE: Bonded
      amalgam restorations prevent over-preparation and reduce the tooth flexure. GIC
      type I under amalgam provides chemical bonding in between amalgam and tooth
      structure and thus reduces the microleakage.

PMID- 21891896
TI  - Expression of heat shock protein70 in oral submucous fibrosis and oral squamous
      cell carcinoma: an immunohistochemical study.
AB  - BACKGROUND: Heat shock proteins are a highly conserved group of protective
      cellular proteins whose synthesis is increased in response to a variety of
      environmental or pathophysiological stresses. Heat shock proteins are useful
      biomarkers for carcinogenesis in tissues and signal the degree of differentiation
      and the aggressiveness of cancers. Regulation of heat shock protein 70 (HSP70)
      expression in oral submucous fibrosis is not known much, and the aim of this
      study was to evaluate HSP70 expression in oral submucous fibrosis and oral
      squamous cell carcinoma by immunohistochemical method and to understand the role
      of HSP70 in tumorigenesis. MATERIALS AND METHODS: Immunohistochemical method was
      used to detect HSP70 expression in normal oral mucosa, oral submucous fibrosis
      (n=30) and oral squamous cell carcinoma (n=20). HSP70 immunoreactivity was
      correlated with histological and clinicopathological features. RESULTS: A
      significant increase in expression of HSP70 was observed (P<0.000) as the tissue
      progressed from oral submucous fibrosis towards oral squamous cell carcinoma.
      CONCLUSION: HSP70 is synthesized upon stress situations arising in cells of all
      living organisms. Expression of HSP70 indicates that stress plays an important
      role as a predisposing factor in oral submucous fibrosis and its subsequent
      progression to oral squamous cell carcinoma.

PMID- 21891897
TI  - Detection of odoriferous subgingival and tongue microbiota in diabetic and
      nondiabetic patients with oral malodor using polymerase chain reaction.
AB  - BACKGROUND: Halitosis has been correlated with the concentration of volatile
      sulfur compounds (VSCs) produced in the oral cavity by metabolic activity of
      bacteria colonizing the periodontal pockets and the dorsum of the tongue. It has
      been assumed that there is a relationship between periodontal disease and
      diabetes mellitus. OBJECTIVES: The aim of the study was to assess the malodor
      using the organoleptic method and tanita device; to quantify odoriferous
      microorganisms of subgingival plaque and tongue coating, such as P. gingivalis
      (Pg), T. forsythia (Tf), and F. nucleatum (Fn) using polymerase chain reaction
      (PCR) in nondiabetic and diabetic chronic periodontitis patients. PATIENTS AND
      METHODS: Thirty chronic periodontitis patients (with and without diabetes) with 5
      7 mm pocket depth, radiographic evidence of bone loss, and presence of oral
      malodor participated in this study. Subjective assessment of mouth air was done
      organoleptically and by using a portable sulfide monitor. Tongue coating was also
      assessed. RESULTS: The scores of plaque index, gingival index, gingival bleeding
      index, VSC levels, and tongue coating between the nondiabetic and diabetic
      patients were not significant (P>0.5). In nondiabetic patients, Fn was found to
      be significantly (P<0.5) more in tongue samples, whereas Pg and Tf have not shown
      significant values (P>0.5). In diabetic patients, Fn and Tf have shown
      significant (P<0.5) an increase in subgingival and tongue samples, respectively,
      whereas Pg has not shown significant difference between subgingival and tongue
      samples. INTERPRETATION AND CONCLUSION: The results confirm that there is no
      difference in clinical parameters between nondiabetic and diabetic periodontitis
      patients, but the odoriferous microbial profiles in tongue samples of diabetic
      patients were found to be high. However, there is a weak positive correlation
      between VSC levels, clinical parameters, and odoriferous microbial profiles.

PMID- 21891898
TI  - A color contrast aided density imaging technique to differentiate between dental
      hard tissues and its relevance.
AB  - AIM: Radiographic interpretation of a disease requires knowledge about normal
      structures. The calcifying jaw diseases can range from radiolucent areas to
      varying degrees of calcification. Therefore, it is vital to differentiate
      radiographically between various hard tissues. MATERIALS AND METHODS: We have
      illustrated the use of computed tomography scan to quantify the calcified
      structures as dentin and enamel in a case of ameloblastic fibro-odontoma.
      RESULTS: The enamel, dentin and cementum showed different values. CONCLUSION: The
      "Dentascan" can be used to distinguish the hard tissues in a variety of
      calcifying diseases of jaws.

PMID- 21891899
TI  - Correlation of periodontal status and bone mineral density in postmenopausal
      women: a digital radiographic and quantitative ultrasound study.
AB  - BACKGROUND: Data suggest that postmenopausal women with osteoporosis are at an
      increased risk for periodontal attachment loss and tooth loss; however, the
      extent of relationship between these two diseases is still not clear. AIM: The
      aim of the study was to evaluate the correlation of periodontal status and bone
      mineral density (BMD) in postmenopausal women. MATERIALS AND METHODS: The study
      population included 60 postmenopausal women aged 50-60 years (mean+/-SD: 55.5+/
      3.4 years). Periodontal status was examined by plaque index, bleeding index,
      probing depth, and clinical attachment level (CAL). Digital panoramic radiograph
      was taken to measure the maxillary and mandibular alveolar bone density values.
      Skeletal (calcaneal) BMD was measured by quantitative ultrasound technique for T
      score values. The recorded data for T-score, maxillary and mandibular alveolar
      bone densities, and periodontal status were subjected to statistical analysis for
      correlation and regression procedures. RESULTS: The results showed that
      mandibular alveolar (r=0.907, P<0.001) and maxillary alveolar bone density
      (r=0.898, P<0.001) had significant positive correlation with calcaneal T-score.
      Probing depth (r=-0.316, P<0.05), bleeding index (r=-0.277, P<0.05), and plaque
      index (r=-0.285, P<0.05) showed weak but significant negative correlation with
      calcaneal T-score and alveolar bone density of both the jaws, whereas CAL showed
      weak correlation with T-score which could not reach to a statistically
      significance level (r=-0.221, P>0.05). CONCLUSION: Calcaneal BMD was related to
      alveolar bone loss and, to a lesser extent, to clinical attachment loss,
      implicating postmenopausal bone loss as a risk indicator for periodontal disease
      in postmenopausal women.

PMID- 21891900
TI  - In vivo bone response and interfacial properties of titanium-alloy implant with
      different designs in rabbit model with time.
AB  - BACKGROUND: Using implants for dental applications are well-accepted procedures
      as one of the solutions for periodontal defect repair. Suitable design and
      materials, their reaction with the surrounding hard tissues and interfacial
      biomechanical properties are still considered to be the primary criteria which
      need to be addressed systematically. In the present study, a thorough and
      systemic approach was made to identify a suitable implant, considering the above
      criteria after both in vitro and in vivo animal trials. MATERIALS AND METHODS:
      Titanium alloy (Ti-6Al-4V) implants, with thread and without thread models, were
      implanted to the mid-metaphysial portion of the tibia of the right hind leg of
      three white Australian Chinchilla rabbit species and their effects and response
      to the surrounding bone were investigated. Parameters studied included
      hematological and biochemical features (serum alkaline phosphatase and calcium),
      both preoperatively and postoperatively, consecutively for 7 days and after 1-3
      months. The interfacial integrity and compositional variation along the interface
      were studied using scanning electron microscope (SEM) with energy dispersive
      analysis of X-ray (EDAX) and histopathology from 1 to 3 months consecutively.
      Finally, biomechanical properties were studied with the help of push-out test.
      RESULTS: Bone remineralization started through the process of electro
      physiological ionic exchanges, which helps in formation of osteoblastic cells in
      the area of bony injury. The SEM-EDAX results confirmed the initial stability for
      the Ti (with thread) implant, but the regeneration of new bone formation was
      faster in the case of Ti (Without thread) implant, and hence could be used for
      faster healing. These have also been substantiated through push-out and
      histopathlogical tests. CONCLUSION: From the physico-chemical and biomechanical
      observations, it was found that that smooth type implants were well accepted in
      the physiological condition although chances of elemental leaching from the
      surface were also observed. Increase of the surface roughness can help into the
      formation of physico-chemical bondage with the surrounding hard tissues.

PMID- 21891901
TI  - A randomized clinical study to assess the reliability and reproducibility of
      "Sign Grading System".
AB  - BACKGROUND: Signs such as +, ++ and +++ for mild, moderate and severe
      stains/calculus are being used in India effectively for more than four decades.
      However, there are no standardized criteria for grading, and no data regarding
      how and when this system was introduced, but it became very popular throughout
      India and is being used since then. AIMS AND OBJECTIVES: An attempt was made here
      to standardize the criteria on which the grades would be given and designate it
      as "Sign Grading System". Along with this, the objective of this paper was to
      evaluate whether this index/system satisfies all the requirements of an ideal
      index, particularly reliability and reproducibility. SETTINGS AND DESIGN: Inter
      examiner and intra-examiner reliability and reproducibility of this index was
      assessed through a randomized clinical study. Patients were recruited from an
      institutional setting by random selection from the outpatient department.
      MATERIALS AND METHODS: One month of training was conducted before the actual
      start of study. The clinical aspect of the study involved 3 investigators and 50
      patients of whom 45 patients were reassessed. All the data were kept blind by a
      research assistant to reduce bias. Necessary measures were taken to
      reduce/eliminate the confounding variables, which could have affected the outcome
      of this study. Cohen's kappa and Fleiss' kappa statistics were employed for
      statistical analysis. RESULTS AND CONCLUSION: The index fulfills most of the
      ideal requirements of an index along with a high degree of reliability and
      reproducibility.

PMID- 21891902
TI  - Periodontal treatment needs in diabetic and non-diabetic individuals: a case
      control study.
AB  - AIM: Diabetes mellitus is a chronic metabolic disorder of the carbohydrate,
      protein and fat metabolism, resulting in increased blood glucose levels. Various
      complications of diabetes have been described with periodontitis being added as
      the sixth complication of diabetes mellitus. The aim of this study was to assess
      periodontal status and treatment needs (TN) in diabetic patients and to compare
      the findings between diabetic and non-diabetic individuals using community
      periodontal index (CPI). MATERIALS AND METHODS: We evaluated the periodontal
      status and periodontal TN in diabetic and non-diabetic individuals in Guwahati,
      Assam. A total of 459 (223 diabetic and 236 non-diabetic) individuals were
      assessed. A person was considered to be diabetic when his blood glucose levels
      were above 140 mg/dl under fasting condition and 200 mg/dl 2 hours
      postprandially. Periodontal status was assessed using CPI. RESULTS: Periodontal
      destruction was found to be increased in diabetic individuals, with periodontal
      destruction increasing with increased blood glucose levels. The necessity of
      complex periodontal treatment also increased with increasing blood glucose
      levels. CONCLUSIONS: Individuals with diabetes are more prone to periodontal
      destruction, and hence, regular periodontal screening and treatment is essential
      in these individuals.

PMID- 21891903
TI  - Effect of occlusal restoration on stresses around class V restoration interface:
      a finite-element study.
AB  - BACKGROUND: Causes of failures in class V restorations have always been
      controversial until now, since the biomechanical aspects of these restorations
      have been understood. AIMS AND OBJECTIVE: This study was aimed to verify the
      hypothesis that eccentric forces are the cause of cuspal flexure, which lead to
      excessive stresses at the periphery of a class V restoration, further it
      identifies the amount of the stress and the flexure increase in the presence of
      an occlusal restoration using different restorative materials to restore (both
      cervical and occlusal) along with their comparison with respect to amount of
      stresses around the cervical restorations. MATERIALS AND METHODS: The study was
      done by modeling a mandibular first premolar which was sectioned bucco-lingually,
      in the NISA, EMRC II finite element software. A 100N eccentric load was applied
      on the tooth structure and stresses were observed at the peripheries of the class
      V restoration when it was restored with composite and with glass ionomer cement.
      The stresses were further analyzed in the presence of occlusal restorations with
      different materials and configurations. RESULTS: It was seen that the stresses at
      the gingival wall interface in case of class V glass ionomer cement was more than
      that for composite. In the presence of an occlusal amalgam restoration, the
      cuspal flexure was more than that of occlusal composite and the stresses at the
      class V peripheries were also statistically significant. CONCLUSION: It was
      suggested that lower modulus composites can flex with the tooth structure
      decreasing the bond failure and that the stresses are much lesser when there is
      absence of an occlusal restoration. Occlusal composite restorations reinforce the
      tooth structure and reduce the cuspal flexure as compared to silver amalgam.

PMID- 21891904
TI  - An electromyographic study to assess the minimal time duration for using the
      splint to raise the vertical dimension in patients with generalized attrition of
      teeth.
AB  - BACKGROUND: To investigate the effect of restoration of lost vertical by centric
      stabilizing splint on electromyographic (EMG) activity of masseter and anterior
      temporalis muscles bilaterally in patients with generalized attrition of teeth.
      MATERIALS AND METHODS: EMG activity of anterior temporalis and masseter muscle
      was recorded bilaterally for 10 patients whose vertical was restored with centric
      stabilizing splint. The recording was done at postural rest position and in
      maximum voluntary clenching for each subject before the start of treatment,
      immediately after placement of splint and at subsequent recall visits, with
      splint and without the splint. RESULTS: The EMG activity at postural rest
      position (PRP) and maximum voluntary clench (MVC) decreased till 1 month for both
      the muscles. In the third month, an increase in muscle activity toward
      normalization was noted at PRP, both with and without splint. At MVC in the third
      month, the muscle activity without splint decreased significantly as compared to
      pretreatment values for anterior temporalis and masseter, while with the splint
      an increase was seen beyond the pretreatment values. CONCLUSION: A definite
      response of anterior temporalis and masseter muscle was observed over a period of
      3 months. This is suggestive that the reversible increase in vertical prior to
      irreversible intervention must be carried out for a minimum of 3 months to
      achieve neuromuscular deprogramming. This allows the muscle to get adapted to the
      new postural position and attain stability in occlusion following splint therapy.

PMID- 21891905
TI  - Evaluation of skeletal maturation by comparing the hand wrist radiograph and
      cervical vertebrae as seen in lateral cephalogram.
AB  - BACKGROUND AND OBJECTIVES: Aim of this study was to determine the validity of
      cervical vertebrae radiographic assessment to predict skeletal maturation.
      MATERIALS AND METHODS: Left-hand wrist and lateral cephalometric radiographs of
      100 Bangalore children aged 8-18 years, divided into 10 groups of 10 subjects
      each with equal distribution of males and females, were measured. On left-hand
      wrist radiograph, the classification of Fishman was used to assess skeletal
      maturation. Cervical vertebrae maturation was evaluated with lateral
      cephalometric radiograph, using the stages developed by Hassel and Farman. The
      changes in hand wrist and cervical vertebrae were correlated. RESULTS:
      Significant association was observed between skeletal maturation indicator stages
      and cervical vertebrae maturation indicator stages. Correlation coefficient was
      found to be significant (P<0.0001). CONCLUSION: The results of the study
      indicated that the cervical vertebrae maturation and hand wrist skeletal
      maturation was significantly related.

PMID- 21891906
TI  - Crestal bone preservation: a review of different approaches for successful
      implant therapy.
AB  - The level of bone crest surrounding the implant is of utmost significance to
      determine osseointegrated implant success, as preservation of marginal bone
      height is highly important for long-term dental implant survival. Various
      approaches have been described in the literature to prevent the crestal bone
      loss, including platform switching, non-submerged approach, scalloped implants,
      implant design modifications, progressive loading, immediate implant placement,
      etc. The purpose of this paper is to review all the possible methods to preserve
      the crestal bone, when each method should be used and their success rates in an
      attempt to address this complex problem of crestal bone resorption. "PubMed" and
      "Google Scholar" were used to find out any studies involving platform switching
      concept from 1990 up to 2009. Twenty-four studies involving methods for
      preservation of crestal bone were evaluated, which included 26% studies on
      platform switching, 22% on non-submerged approach, 17% on scalloped implants, 13%
      on progressive loading and 22% on immediate implant placement. Crestal bone
      preservation should be thought of starting from the design of the implant to be
      placed. The technique to be followed in a given case will depend upon the density
      of bone, force factors by the patient, bone volume and amount of soft tissues,
      etc. The best possible method or the combination of the methods should be used to
      preserve the crestal bone for the long-term success of the implants.

PMID- 21891907
TI  - Probiotics and prebiotics in periodontal therapy.
AB  - There has been a paradigm shift toward ecological and microbial community-based
      approach in understanding oral diseases. A marked improvement in gastrointestinal
      health has been reported after using probiotic bacteria and/or prebiotic
      supplements,which has prompted much interest in the use of this approach for oral
      applications. Treatment of periodontal disease in recent years has moved toward
      an antibiotic/antimicrobial model of disease management. With increase in the
      incidence of resistance to antibiotics, probiotics may be a promising area of
      research in periodontal therapy. This paper reviews the evidences for the use of
      probiotics or prebiotics for the prevention of dental caries or periodontal
      diseases, and also adresses the risk associated with their prolonged use. Many
      questions have been raised pertaining to the benefits of probiotic
      administration, as the role of probiotics in periodontics is still in infancy,
      and a complete understanding of the broad ecological changes induced in the mouth
      by probiotics or prebiotics is essential to assess their long-term consequences
      for oral health and disease.

PMID- 21891908
TI  - Sequence of oral manifestations in rhino-maxillary mucormycosis.
AB  - Mucormycosis, caused by saprophytic fungi of the order Mucorales of the class
      Zygomycetes, is a rare opportunistic fungal infection, which has a rapidly
      progressive and fulminant course with fatal outcome. These fungi are ubiquitous,
      found in soil, bread molds, decaying fruits and vegetables. The most common form
      of mucormycosis is rhinocerebral and is usually seen in uncontrolled diabetes
      mellitus or in immunocompromised patients. This fungus invades the arteries,
      leading to thrombosis that subsequently causes necrosis of hard and soft tissues.
      We report a case of palatal perforation by rhino-maxillary mucormycosis in an
      immunocompromised patient. The aim of this article is to draw attention to the
      clinical presentation and pathogenesis of mucormycosis and to emphasize the need
      for high degree of suspicion in its diagnosis and management.

PMID- 21891909
TI  - Sialocele: an unusual case report and its management.
AB  - A post traumatic parotid sialocele is an acquired lesion that arises from
      extravasation of saliva into glandular or periglandular tissues secondary to
      disruption of the parotid duct or parenchyma. Facial trauma and surgery in the
      parotid region are the most common causes of this rare condition. This paper
      presents an unusual incidence of post traumatic parotid sialocele after Le-Fort
      II fracture reduction and its management by relatively simple and cost-effective
      technique which can be carried out in routine dental surgery suite. The results
      achieved justify our recommendation of scalp vein cannula for the treatment of
      sialocele in clinical practice.

PMID- 21891910
TI  - Burkitt's lymphoma in leukemic phase in an Indian boy.
AB  - Burkitt's lymphoma (BL) is the most common childhood cancer in Africa and is most
      prevalent in areas endemic for malaria. The disease, a malignant growth of
      lymphoid tissue, usually presents itself as a large tumor of the jaw. It is
      however, a rarity in the Indian subcontinent. Through an extensive literary
      survey, it is seen that only a few cases of BL have been reported, accounting for
      only 0.76% of solid malignant tumors among Indian children. Here we present a
      case of BL of mandible extending to maxilla in a 13-year-old boy of Indian
      origin.

PMID- 21891911
TI  - Ameloblastic fibrodentinoma.
AB  - Odontogenic tumors comprise a complex group of lesions of diverse
      histopathological types and clinical behavior. The group of mixed odontogenic
      tumors, which are also rare, is composed of proliferating odontogenic epithelium
      in a cellular ectomesenchyme resembling dental papilla. Ameloblastic
      fibrodentinoma is a rare benign odontogenic tumor. The present case report
      discusses this tumor composed of odontogenic epithelium and odontogenic
      mesenchyme with dentin or dentin like tissue. The present paper also throws light
      on various histological similarities and complexities which make the
      interpretation of these set of odontogenic tumors a diagnostic dilemma.

PMID- 21891912
TI  - Prosthodontic management of anhidrotic ectodermal dysplasia.
AB  - Ectodermal dysplasia is characterized by the absence or defects of two or more
      ectodermally derived structures. Anodontia or hypodontia is the most striking
      dental manifestation. In severe hypodontia, there is lack of alveolar development
      with consequent protrusion and eversion of the lips. Patients with anhidrotic
      forms suffer from heat intolerance due to lack of sweat glands and mild
      infections may lead to death in infancy from hyperthermia. A case of a 4-year-old
      child with anhidrotic ectodermal dysplasia with partial anodontia is presented.
      Dental, oral, and physical features were taken into consideration in diagnosis
      and treatment planning for this patient. Clinical management consisted of
      removable partial prosthesis in maxillary arch and complete denture prosthesis in
      mandibular arch. The main aim of the treatment was to improve psychological
      development and to promote better functioning of the stomatognathic system.

PMID- 21891913
TI  - Cemento-ossifying fibroma.
AB  - Cemento-ossifying fibromas (COFs) are benign lesions affecting the jaws and other
      craniofacial bones. They commonly affect adult females between the third and
      fourth decade of life, predominantly occurring in the premolar/molar region of
      the mandible. Most of the lesions typically show slow and often expansile growth,
      centrally within the jaw and characteristically behave in a benign form, but
      occasionally they may present as an aggressive gigantiform lesion.
      Radiographically, they appear as well-defined unilocular or multilocular
      intraosseous masses. The lesion is invariably encapsulated and of mixed
      radiolucent densities. The tumor may grow quite extensively; thus, the term
      "aggressive" is sometimes applied. Surgical resection is the treatment of choice.
      They are insensitive to radiotherapy and recurrences are uncommon. Clinical,
      radiographic and histopathologic features of COF and other fibro-osseous lesions
      are overlapping and may cause confusion in classification, diagnosis and
      treatment.

PMID- 21891914
TI  - Impact of delayed prosthetic treatment of velopharyngeal insufficiency on quality
      of life.
AB  - Palatopharyngeal dysfunction may take place when palatopharyngeal valve is unable
      to perform its own closing due to a lack of tissue (palatopharyngeal
      insufficiency) or lack of proper movement (palatopharyngeal incompetence).
      Palatopharyngeal insufficiency induces nasal regurgitation of liquids, hypernasal
      speech, nasal escape, disarticulations and impaired speech intelligibility.
      Prosthetic management of palatopharyngeal insufficiency requires a close co
      operation between an otolaryngologist and a speech pathologist. As a result, the
      patient can be socially and physically rehabilitated with the improved speech
      quality as well as prevention of leakage of liquids.

PMID- 21891915
TI  - Overdenture with accesspost system: a clinical report.
AB  - A patient presented with an unfavorable distribution of teeth in the arch which
      precluded treatment with a removable partial denture. The unique pattern of
      partial edentulism was treated with an overdenture restoration using accesspost
      system. The final restoration was stable, well retained and esthetic, serving as
      a conservative approach to root preservation.

PMID- 21891916
TI  - Immunohistochemical detection of human telomerase reverse transcriptase in oral
      cancer and pre-cancer.
AB  - PURPOSE: Telomerase is a specialized ribonucleoprotein complex that stabilizes
      telomeres by adding "TAG" repeats to the end of chromosomes. The catalytic
      subunit of telomerase is human telomerase reverse transcriptase (hTERT), whose
      expression is the critical determinant of telomerase activity. Telomeres and
      telomerases play an important role in the longevity of cell and are known to
      conform "immortalization" on neoplastic cells. Although there exists a lot of
      information on telomerase in oral cancer, very little is known about their
      expression in leukoplakia and oral submucous fibrosis (OSF). This study addresses
      this lacuna. MATERIALS AND METHODS: In this preliminary study,
      immunohistochemistry (IHC) was used to detect the expression of hTERT protein in
      oral squamous cell carcinoma (OSCC) (n=30), leukoplakia (n=15), OSF (n=15) and
      normal oral mucosa (n=10). The cellular localization of immunostain, intensity of
      stain, mean nuclear labeling index (LI) and mean nuclear labeling score (LS) of
      hTERT protein were studied. A total number of 1000 cells were counted in each
      slide. All the data were analyzed using SPSS software version 10.0.2. The
      cellular localization of cytoplasmic/nuclear/both of hTERT stain, staining
      intensity and LI were compared across the groups using Pearson's chi2 test. The
      mean LI and LS for OSF, leukoplakia, OSCC and normal were compared using analysis
      of variance (ANOVA). A P-value <0.05 was considered to be statistically
      significant. RESULTS: The mean nuclear LI increased from OSF (22.46+/-4.53),
      through normal (28.3+/-12.3) to OSCC (47.56+/-21.30) (P=0.002) and from normal
      (28.3+/-12.3), through leukoplakia (44.06+/-14.6), to OSCC (47.56+/-21.30)
      (P=0.00). The mean nuclear labeling score was observed to increase from OSF
      (37.8+/-15), through normal (64.9+/-30.7), to OSCC samples (106.9+/-29.77)
      (P=0.00) and from normal (64.9+/-30.7), through leukoplakia (85.6+/-25.1) to OSCC
      samples (106.9+/-29.77) (P=0.00). CONCLUSION: There was increased expression of
      hTERT protein in OSCC and leukoplakia samples when compared to normal oral
      mucosa. The cellular localization, LI and LS in OSF were significantly different
      from OSCC and leukoplakia.

PMID- 21891917
TI  - Reliability of Logicon caries detector in the detection and depth assessment of
      dental caries: an in-vitro study.
AB  - BACKGROUND: Digital radiography has so far not resulted in improved rates of
      proximal caries detection. Historically, automated caries detection tools have
      been largely academic. Opinions regarding the performance of the only such
      commercially available tool, viz., Logicon caries Detector (LCD) have been
      equivocal. This study was conducted to evaluate the reliability of LCD in the
      detection and depth assessment of proximal caries. MATERIALS AND METHODS: Digital
      images were obtained of 100 proximal tooth surfaces using the Kodak RVG 5000
      sensor and analyzed by three observers. The images were then analyzed by the
      principal investigator using the LCD software. The teeth were then sectioned and
      magnified photographic images were obtained which were taken as the gold
      standard. All the grades were entered in proformas and the data were
      statistically analyzed using the chi-square test. Five parameters of reliability
      were calculated. RESULTS: The sensitivity, specificity, positive predictive
      value, negative predictive value, and overall accuracy of LCD for the grade No
      caries were 33, 96, 73, 82, and 81%, respectively; for the grade Enamel caries
      were 5, 97, 33, 80, and 79%, respectively; and for the grade Dentin caries were
      100, 96, 50, 100, and 96%, respectively. CONCLUSIONS: In conclusion, LCD appears
      to be more reliable in ruling out (both enamel and dentin) caries than in
      detecting caries.

PMID- 21891918
TI  - Rotary Mtwo system versus manual K-file instruments: efficacy in preparing
      primary and permanent molar root canals.
AB  - AIM: To compare the cleaning ability and preparation time of rotary instruments
      (Mtwo) and conventional manual instruments (K-file) in preparing primary and
      permanent molar root canals. MATERIALS AND METHODS: Access cavities were prepared
      in 70 primary and 70 permanent teeth and India ink was injected into 120 canals
      of selected molars. The teeth were randomly divided into two main subgroups
      (n=20) and three control groups (n=10). In each of these main subgroups, either
      the manual instrument (K-file) or the rotary system (Mtwo) was used to prepare
      root canals. After cleaning the canals and clearing the teeth, dye removal was
      evaluated with the help of a stereomicroscope. In addition, the time needed for
      root canal preparation was recorded by a chronometer. STATISTICAL ANALYSIS:
      Statistical analyses were done using the Kruskal-Wallis, Mann-Whitney and t
      tests. RESULTS: With regard to the cleaning ability of root canals, there were no
      significant differences between the K-file and Mtwo rotary system in primary and
      permanent teeth in the apical, middle or coronal third of the canals. Moreover,
      there were no significant differences between primary and permanent teeth
      prepared with K-files and rotary instruments. In all the groups, shorter times
      were recorded with the rotary technique. The working time was shorter in primary
      than in permanent teeth. CONCLUSION: The Mtwo rotary system showed acceptable
      cleaning ability in both primary and permanent teeth, and achieved results
      similar to those of K-files in less time.

PMID- 21891919
TI  - Glandular odontogenic cyst: report of an unusual bilateral occurrence.
AB  - Glandular odontogenic cyst (GOC) is a recently recognized rare developmental
      odontogenic cyst having an aggressive behavior and accounting for 0.012% to 1.3%
      of all jaw cysts. GOC usually presents as a painless, slow-growing swelling that
      tends to affect the anterior part of the jaws. It chiefly occurs in the fourth
      and fifth decades of life and presents as an expansion of jaws with or without
      pain or paresthesia. Aggressive nature of the lesion has been reported, as
      supported by the fact that 25 to 55% of cases recur following curettage. So far
      only just over 113 cases of GOC have been reported in the literature. Here, we
      report a case of bilateral GOC in the posterior region of the maxilla, in a 29
      year-old male patient, which is unique, being the first case of bilateral GOC to
      be reported in the literature.

PMID- 21891920
TI  - Prevalence of permanent tooth loss among children and adults in a suburban area
      of Chennai.
AB  - AIM: To determine the prevalence of permanent tooth loss among children and
      adults in a suburban area of Chennai. DESIGN: Cross sectional descriptive study.
      STUDY SETTING: The study was conducted in Tiruverkadu, a suburban area of
      Chennai. MATERIALS AND METHODS: A house-to-house survey was done in Tiruverkadu.
      The study population consisted of 6, 12, 15 years children, 35-44 years, and 65
      74 years adults. Type III dental examination was carried out. Cross tabulations
      and Chi-square statistics were computed. The level of significance was chosen as
      P<0.05. RESULTS: Out of the total 679 subjects, 309 subjects had tooth loss.
      Females (47.9%) had greater tooth loss compared to males (42.9%). Tooth loss
      increased as age progressed. Subjects in the lower socio-economic status had
      greatest tooth loss. The mean tooth loss among the subjects was 2.7. CONCLUSION:
      This study indicates that tooth loss increases with age and differs for gender
      and socio-economic status. The prevalence of tooth loss among the subjects was
      found to be high in children as well as in adults. Therefore, dental
      professionals should utilize various measures available in preventive dentistry
      to minimize tooth loss.

PMID- 21891921
TI  - The application of intraoperative fluorescence utilizing 5-aminolevulinic acid in
      detection of residual cerebellar hemangioblastoma following visually assessed
      gross total resection.

PMID- 21891922
TI  - Management of prolactinomas: the fine print between the lines!

PMID- 21891923
TI  - Chronic encapsulated intracerebral hematoma.

PMID- 21891924
TI  - Spontaneous intracranial hypo and hypertensions: an imaging review.
AB  - Cerebrospinal fluid (CSF) pressure changes can manifest as either intracranial
      hypertension or hypotension. The idiopathic forms are largely under or
      misdiagnosed. Spontaneous intracranial hypotension occurs due to reduced CSF
      pressure usually as a result of a spontaneous dural tear. Idiopathic intracranial
      hypertension (IIH) is a syndrome of elevated intracranial tension without
      hydrocephalus or mass lesions and with normal CSF composition. Neuroimaging plays
      an important role in excluding secondary causes of raised intracranial tension.
      As the clinical presentation is varied, imaging may also help the clinician in
      arriving at the diagnosis of IIH with the help of a few specific signs. In this
      review, we attempt to compile the salient magnetic resonance imaging findings in
      these two conditions. Careful observation of these findings may help in early
      accurate diagnosis and to provide appropriate early treatment.

PMID- 21891925
TI  - Immunohistochemical differentiation of inflammatory myopathies.
AB  - BACKGROUND: Idiopathic inflammatory myopathies are a heterogeneous group of
      acquired muscle disorders with considerable overlap in the histological features,
      making histological diagnosis difficult at times. AIMS: To determine the
      immunohistochemical profile of clinically suspected cases of inflammatory
      myopathies, using monoclonal antibodies to HLA-1 and membrane attack complex
      (MAC), and to correlate the clinical, serological, and electromyographic profile
      and the histopathological picture, with the immunohistochemical profile. SETTINGS
      AND DESIGN: This was a retrospective study analyzing the clinical and
      histopathological features in muscle of clinically suspected cases of
      inflammatory myopathy and correlating it to their HLA-1 and MAC immunostaining
      profiles. MATERIAL AND METHODS: The study subjects included 33 cases with
      suspected inflammatory myopathy and 59 with non-inflammatory muscle disease, as
      controls. Clinical data, electromyographic findings, serological profile, and
      details of therapy were obtained from patient records. STATISTICAL ANALYSIS:
      Student 'T' test, Pearson's Chi square test, and Kappa statistics were used
      appropriately. RESULTS: Although HLA-1 and MAC immunostaining did not help to
      differentiate the individual subtypes of inflammatory myopathy, when either HLA-1
      or MAC was positive, inflammatory myopathy could be ruled in with 86.5% certainty
      and when both HLA-1 and MAC were negative, it could be ruled out with 95%
      certainty. CONCLUSIONS: A combination of clinical presentation, serological
      profile, electromyographic and histopathological features, together with the
      immunoprofile for HLA-1 and MAC, contribute toward making a diagnosis of
      inflammatory myopathy.

PMID- 21891926
TI  - Association of atherosclerotic cerebral infarction and human leukocyte antigen
      DRB in a North Chinese Han population.
AB  - BACKGROUND AND OBJECTIVES: Evidence from experimental and genetic studies suggest
      the existence of a potential link between the polymorphisms of human leukocyte
      antigen class II gene (HLA-DR) and ischemic stroke. This study addressed the
      association of HLA-DR gene with atherosclerotic cerebral infarction (ACI) in a
      North Chinese Han population. MATERIAL AND METHODS: The genotyping of HLA-DRB1
      was determined by standard techniques based on polymerase chain reaction and
      sequence-specific oligonucleotides hybridization in a gene chip. RESULTS: The
      relative risk (RR) of HLA-DRB1 FNx01 04 and HLA-DRB1 FNx01 03 (17) in patients
      with ACI and their first-degree relatives were significantly higher than those in
      the control group (RR=2.56 and 18.77, respectively; P <0.05). In contrast, the RR
      of HLA-DRB1 FNx01 12 was dramatically reduced in patients with ACI in relation to
      healthy controls (RR=0.17; P <0.01). CONCLUSIONS: These data indicate that the
      polymorphisms in HLA-DRB1 may influence the risk of ACI in the North Han
      population of China. Further studies are necessary to validate the observation in
      larger samples.

PMID- 21891927
TI  - Expression patterns of two potassium channel genes in skeletal muscle cells of
      patients with familial hypokalemic periodic paralysis.
AB  - BACKGROUND: Familial hypokalemic periodic paralysis is an autosomal-dominant
      disorder characterized by episodic attacks of muscle weakness with hypokalemia.
      The combination of sarcolemmal depolarization and hypokalemia has been attributed
      to abnormalities of the potassium conductance governing the membrane potential;
      however, the molecular mechanism that causes hypokalemia has not yet been
      determined. AIM: To test the hypothesis that the expression patterns of delayed
      rectifier potassium channel genes in the skeletal muscle cells of patients with
      familial hypokalemic periodic paralysis differ from those in normal cells.
      MATERIAL AND METHODS: We examined both mRNA and protein levels of two major
      delayed rectifier potassium channel genes KCNQ3 and KCNQ5 in the skeletal muscle
      cells from three patients with familial hypokalemic periodic paralysis and three
      healthy controls. RESULTS: When normal cells were exposed to 50 mM potassium
      buffer, which was used to induce depolarization, the KCNQ3 protein level
      significantly increased in the membrane fraction but decreased in the cytosolic
      fraction, whereas the opposite was true in patient cells. CONCLUSION: Abnormal
      subcellular distribution of the KCNQ3 protein was observed in patient cells. Our
      results suggest that the altered expression of KCNQ3 in patient cells exposed to
      high extracellular potassium levels could possibly hinder normal function of the
      channel protein. These findings may provide an important clue to understanding
      the molecular mechanism of familial hypokalemic periodic paralysis.

PMID- 21891928
TI  - Microsurgical management of prolactinomas - clinical and hormonal outcome in a
      series of 172 cases.
AB  - AIMS AND OBJECTIVES: To report hormonal outcome after surgery in a special
      subgroup of prolactinomas in whom medical therapy is not effective or not
      indicated. PATIENTS AND METHODS: All patients who underwent surgery for
      prolactinomas, between December 2002 and December 2009, were analyzed
      retrospectively. The study group consisted of patients who were either intolerant
      or noncompliant to dopamine agonist (DA) therapy or those in whom medical
      treatment could not be given due to various reasons. The surgical results were
      assessed according to whether patients had microadenoma (<1 cm diameter),
      macroadenoma (>1 cm diameter), or giant prolactinoma (>4 cm diameter). Initial
      and final hormonal remission was defined as normalization of serum prolactin
      levels (<25 ng/ml) at 7 days after surgery and at last follow up, respectively.
      RESULTS: Of the 172 patients, 133 (77%) were operated by primary transsphenoidal
      approach and 25 (14.5%) were operated transcranially and 14 patients required
      reoperation, either transsphenoidally (6 patients) or transcranially (8
      patients). Overall, at last follow-up, hormonal remission could be achieved in
      44% patients (83% microadenomas, 48% macroadenomas, and 16% of giant adenomas).
      There were three deaths (1.7%), 12 patients (7%) had single/multiple
      postoperative treatable complications. 59% of those patients, who did not achieve
      remission after surgery, finally attained normoprolactinemia with either DA
      therapy or radiotherapy, at last follow-up. CONCLUSIONS: Medical treatment of
      prolactinomas with DA should be considered as treatment of choice for these
      tumors. However, there is a major subgroup of patients who respond better to
      surgery rather than protracted medical therapy.

PMID- 21891929
TI  - Radial artery grafts for symptomatic cavernous carotid aneurysms in elderly
      patients.
AB  - BACKGROUND: Radial artery grafts (RAG) have been used in the treatment of complex
      vascular lesions, but not for symptomatic cavernous carotid aneurysms in elderly
      patients. AIM: To investigate the safety, usefulness, and perioperative
      complications of RAGs for symptomatic cavernous carotid aneurysms in elderly
      patients. MATERIAL AND METHODS: Of the 74 consecutive patients, in whom RAGs were
      used, we retrospectively investigated the postoperative outcomes and
      complications in eight elderly patients aged over 70 years with symptomatic
      internal carotid artery aneurysms in cavernous sinus. RESULTS: Postoperative
      complications included one case of cerebral infarction, one case of symptomatic
      seizures, and one case of delayed cranial nerve palsy. OUTCOME: Seven patients
      had an mRS score of 0, and one patient had a score of 2. Postoperatively there
      was improvement in cranial nerve palsy in seven patients and the patients who had
      symptoms for one year and eight months had residual deficits. Although it cannot
      be stated that the frequency of perioperative complications was low, the final
      outcomes were favorable. CONCLUSION: Even in carotid disease that is difficult to
      treat among the elderly, RAG would appear to be a useful and safe treatment.

PMID- 21891930
TI  - Management outcome of the transcallosal, transforaminal approach to colloid cysts
      of the anterior third ventricle: an analysis of 78 cases.
AB  - BACKGROUND: Colloid cysts are not common brain lesions and account for 0.2-2.0%
      of all brain lesions. Transcallosal, transforaminal approach is a safe route and
      the most direct path to excise third ventricular colloid cyst, without dependence
      on hydrocephalus. AIM: To assess the surgical outcome of patients with colloid
      cysts of the anterior third ventricle treated by the transcallosal,
      transforaminal approach. PATIENTS AND METHODS: Seventy-eight patients operated by
      the above approach over a period of 20 years were analyzed. A pre- and
      postoperative neurological assessment was done in all the patients. Neuro
      cognitive evaluation of corpus callosum function was done in the last 20
      patients. Computer tomography scan of the brain was done in all patients pre- and
      postoperatively. RESULTS: Clinical features of raised intracranial pressure
      without localizing signs were the commonest presenting feature in 52 (66.7%)
      patients. Hydrocephalus was present in 65 (83.3%) patients. All patients
      underwent the transcallosal, transforaminal approach, and total excision of the
      lesion was achieved in 77 patients and subtotal in 1. Four patients required a
      postoperative shunt for acute hydrocephalus. There was no incidence of
      postoperative disconnection syndrome. In two patients, there was recurrence of
      the lesion after 2 and 6 years, respectively. Two patients died in the
      postoperative period. CONCLUSION: Colloid cyst is surgically curable. Early
      detection and total excision of the lesion can be a permanent cure with low
      mortality and minimum morbidity, when compared to the natural history of the
      disease. The limited anterior callosotomy does not result in disconnection
      syndromes or behavioral disturbance.

PMID- 21891932
TI  - Stem cell therapy for brain disorders: why results are discordant?

PMID- 21891931
TI  - Endovascular treatment for wide-necked intracranial aneurysms with the Enterprise
      stent.
AB  - BACKGROUND: The development of self-expanding stents dedicated to intracranial
      use has significantly widened the applicability of endovascular therapy to many
      intracranial aneurysms OBJECTIVE: To report the angiographic and clinical
      outcomes of wide-necked intracranial aneurysms treated using the Enterprise
      stent. MATERIAL AND METHODS: Forty-six patients with 50 wide-necked and fusiform
      aneurysms (19 aneurysms with dissections), admitted between June 2009 and
      December 2010, were treated using Enterprise stents. Demographic information,
      procedural data, and technical complication were reviewed. Angiographic and
      clinical outcomes were evaluated at a 9.1-month follow-up. RESULTS: Stent
      deployment was successful in all the 50 lesions, and additional coil embolization
      was performed in 48. Complete or near-complete occlusion immediately after stent
      deployment was achieved in 44 aneurysms, whereas, no immediate coil embolization
      was chosen in two cases. There was one (2%) procedure-related complication, which
      resulted in death. At mean 9.1-month follow-up, the result was good (GOS <=2) in
      45 patients. Angiographic recurrences arose in two cases, one of which was re
      treated completely. CONCLUSIONS: The Enterprise stent is very useful for
      endovascular embolization of wide-necked intracranial aneurysms, because it is
      easy to navigate and place precisely. The overall morbidity and mortality rates
      are low.

PMID- 21891933
TI  - Induced pluripotent stem cells and promises of neuroregenerative medicine.
AB  - First created in 2006 from adult somatic cells by a simple molecular genetic
      trick, induced pluripotent stem cells (iPS) system is the latest platform in stem
      cell research. Induced pluripotent stem cells are produced by nuclear
      reprogramming technology and they resemble embryonic stem cells (ES) in key
      elements; they possess the potentiality to differentiate into any type of cell in
      the body. More importantly, the iPS platform has distinct advantage over ES
      system in the sense that iPS-derived cells are autologous and therefore the iPS
      derived transplantation does not require immunosuppressive therapy. In addition,
      iPS research obviates the political and ethical quandary associated with embryo
      destruction and ES research. This remarkable discovery of cellular plasticity has
      important medical implications. This brief review summarizes currently available
      stem cell platforms, with emphasis on cellular reprogramming and iPS technology
      and its application in disease modeling and cell replacement therapy in
      neurodegenerative diseases.

PMID- 21891934
TI  - Pluripotent stem cells - a review of the current status in neural regeneration.
AB  - Pharmacological or neurosurgical therapies currently in practice to treat the
      damage in various neurodegenerative disorders are not efficient in preventing
      progression or cure of these progressive neurodegenerative processes. Recently, a
      new approach, cell therapy using stem cell, is being evaluated. However, the use
      of this therapy in the treatment of these neurological diseases is highly
      restricted, mainly owing to several technical difficulties and limitations. The
      strategy of isolation and characterization of neural stem cells from various
      sources will probably provide a major impetus and open up an interesting, novel
      therapeutic modality for several neurodegenerative disorders. The high
      regenerative potential of damaged neural tissues suggests that various
      embryonic/adult sources serve as a proxy for neural stem cells for cell-based
      therapy.

PMID- 21891935
TI  - Motor recovery following olfactory ensheathing cell transplantation in rats with
      spinal cord injury.
AB  - BACKGROUND: Olfactory ensheathing cells (OEC) are considered to be the most
      suitable cells for transplantation therapy in the central nervous system (CNS)
      because of their unique ability to help axonal regrowth and remyelination in the
      CNS. However, there are conflicting reports about the success rates with OEC.
      AIM: This study was undertaken to evaluate the therapeutic effect of OEC in rat
      models using different cell dosages. MATERIAL AND METHODS: OECs harvested from
      the olfactory mucosa of adult white Albino rats were cultured. Spinal cord injury
      (SCI) was inflicted at the lower thoracic segment in a control and test group of
      rats. Two weeks later, OECs were delivered in and around the injured spinal cord
      segment of the test group of the rats. The outcome in terms of locomotor recovery
      of limb muscles was assessed on a standard rating scale and by recording the
      motor-evoked potentials from the muscles during transcranial electrical
      stimulation. Finally, the animals were sacrificed to assess the structural repair
      by light microscopy. STATISTICAL ANALYSIS: Wilcoxon signed rank test and Mann
      Whitney U-test were used to compare the data in the control and the test group of
      animals. A P value of <0.05 was considered significant. RESULTS: The study showed
      a moderate but significant recovery of the injured rats after OEC transplantation
      (P=0.005). CONCLUSION: Transplantation of OECs along with olfactory nerve
      fibroblasts improved the motor recovery in rat models with SCI.

PMID- 21891936
TI  - Intralesional mesenchymal stromal cell transplant in a rodent model of cortical
      cryoinjury.
AB  - BACKGROUND: The effect of intralesional mesenchymal stromal cell (MSC) transplant
      in the subacute phase of brain injury has not been studied. AIM: To evaluate the
      role of intralesional transplant of mouse MSC following coldinduced cerebral
      cortical injury in mouse in improving neurological function. MATERIAL AND
      METHODS: Twelve mice (Swiss albino strain) received an intralesional injection of
      2*106 mouse MSCs labelled with Bromodeoxyuridine (BrdU) and suspended in
      phosphate-buffered saline (PBS), 72 h after cerebral cryoinjury. Six mice
      received intralesional injection of PBS and served as controls. Neurological
      severity score (NSS) and rotarod treadmill test were used to perform serial
      assessments. RESULTS: The mean NSS in the control group (n=5) on the first
      posttrauma day was 9.3+/-1.2 and it improved to 14.2+/-1.3 on day 28. The mean
      NSS in the MSC group (n=11) was 10.7+/-1.8 on the first posttrauma day and it
      improved to 16+/-1.1 on day 28 posttransplant. This difference was not found to
      be statistically significant when subgroup analysis of animals, where the
      assessments were blinded, was performed. There was no significant difference in
      the rotarod treadmill scores between the control and the MSC group at any time
      point. Few BrdU-positive cells could be identified in the periphery of the
      contusion up to day 10 posttransplant. CONCLUSIONS: Transplanted MSCs were shown
      to survive for at least 10 days after intralesional transplant in the cryoinjury
      model of the mouse cerebral cortex but the functional recovery observed in the
      experimental group was not statistically different from the controls.

PMID- 21891937
TI  - Combination of NEP 1-40 infusion and bone marrow-derived neurospheres
      transplantation inhibit glial scar formation and promote functional recovery
      after rat spinal cord injury.
AB  - BACKGROUND AND AIMS: Studies have shown that administration of NEP1-40, a Nogo-66
      receptor antagonist peptide, improves locomotor recovery in rats. We hypothesize
      that combining NEP1-40 with another promising therapy, neural stem cell
      transplantation, might further improve the degree of locomotor recovery. In the
      present study, we examined whether NEP1-40 combined with bone marrow stromal
      cells-derived neurospheres (BMSC-NSs) transplantation would produce synergistic
      effects on recovery. MATERIAL AND METHODS: Adult Sprague-Dawley rats were
      subjected to spinal cord injury (SCI) at the T10 vertebral level. Immediately
      after injury, rats were administrated NEP1-40 intrathecally for 4 weeks. BrdU
      labeled BMSC-NSs (2*105 ) were transplanted into the injured site 7 days after
      SCI. Locomotor recovery was assessed for 10 weeks with BBB scoring. Animals were
      perfused transcardially 10 weeks after contusion, and histological examinations
      were performed. RESULTS: The combined therapy group showed statistically better
      locomotor recovery than the control group at 7 weeks of contusion. Neither of the
      two single-agent treatments improved locomotor function. The average area of the
      cystic cavity was significantly smaller in the combined therapy group than in the
      control group. Fluorescence microscopic analysis showed that NEP1-40 dramatically
      inhibited the formation of glial scar and promoted the axons penetration into the
      scar barrier. CONCLUSION: This study revealed that BMSC-NSs and NEP 1-40 exhibit
      synergistic effects on recovery in rat SCI. This may represent a potential new
      strategy for the treatment of SCI.

PMID- 21891938
TI  - Spectrum of neurological manifestations of idiopathic hypoparathyroidism and
      pseudohypoparathyroidism.
AB  - We describe clinical, biochemical, radiological profile, and treatment outcome in
      97 patients with idiopathic hypoparathyroidism seen over a period of 18 years. Of
      the 97 patients, 78 (80%) had idiopathic hypoparathyroidism and 19 (20%) had
      pseudohypoparathyroidism. The mean age+/-standard deviation (SD) at presentation
      was 28.7+/-14.1 years. There were 52 males, the mean lag time from first reported
      symptom to diagnosis was 5.9+/-5.2 years and the mean (+/-SD) follow-up was 1.8+/
      0.4 years. The most common presenting manifestation was carpopedal spasm in 68
      (70%) patients, followed by paresthesia and seizures in 52 (54%) patients. The
      mean (+/-SD) serum calcium and inorganic phosphate concentrations were 6.1+/-1.5
      mg/dl and 6.3+/-1.5 mg/dl, respectively. The most common imaging abnormality
      noted was basal ganglia calcification followed by cerebral cortex and cerebellum
      calcification. More than one-third of patients were on various antiepileptic
      drugs including phenytoin. In addition to oral calcium and active vitamin D
      (calcitriol), twenty-six patients (27%) also required hydrochlorothiazide. The
      important finding in our study was long lag time from the first reported symptom
      to diagnosis. Phenytoin was the drug in almost one- third of our patients with
      seizures. Practicing clinicians should have high index of suspicion of diagnosis
      hypoparathyroidism in the appropriate clinical states to avoid the morbidity
      associated with hypoparathyroidism. Phenytoin should be avoided in patients with
      hypoparathyroidism and seizures.

PMID- 21891939
TI  - Use of O-arm for spinal surgery in academic institution in India: experience from
      JPN apex trauma centre.
AB  - There is a relatively high incidence of screw misplacement during spinal
      instrumentation due to distortion of normal anatomy following spinal trauma. The
      O-arm(r) is the next-generation spinal navigation tool that provides
      intraoperative 3-D imaging for complex spine surgeries. In this prospective study
      over 1-month period, 25 patients (mean age 29.16 years (range 7-58 years), 22
      (88%) males) with spinal injury who underwent spinal instrumentation under O
      arm(r) guidance were included. Fall from height (64%) was the most common
      etiology seen in 16 patients. The majority (68%) had dorsolumbar fractures.
      Spinal canal compromise was seen in 21 patients (84%). Ten patients (40%) had
      American Spinal Injury Association (ASIA) grade A injuries, two patients (8%) had
      grade B, five patients (20%) had grade C, four patients (16%) each had grade D,
      and grade E injuries. A total of 140 screws were inserted under O-arm guidance.
      Of these, 113 (81%) were dorsolumbar pedicle screws, 2 were odontoid screws, 12
      were anterior cervical screws, and 12 screws (48%) were lateral mass screws. Mean
      duration of surgery was 4.5 h with a mean blood loss of 674 mL. The mean
      postoperative stay was 6.3 days. None of the patients had screw malplacement ort
      canal breach. No patient deteriorated in ASIA grade postoperatively. The system
      was rated as excellent for ease of use by all faculty using the system. Accurate
      screw placement provides better patient safety and reduces the in hospital stay
      thereby leading early patient mobilization and may reduce the cost incurred in
      patient management.

PMID- 21891940
TI  - Herpes simplex virus encephalitis complicated by intracerebral hematoma.
AB  - Herpes simplex virus (HSV) encephalitis complicated by cerebral hematoma is
      extremely rare. We report a 54-year-old man with hepes simplex encephalitis
      complicated by intracerebral hematoma and review the literature and describe the
      characteristics of HSV encephalitis complicated by intracerebral hematoma.

PMID- 21891941
TI  - Balo's concentric sclerosis involving bilateral thalami.
AB  - Balo's concentric sclerosis (BCS) is a rare inflammatory demyelinating disease of
      central nervous system, pathologically characterized by alternate bands of
      demyelination and preserved myelin tissue. Before the era of magnetic resonance
      imaging (MRI), most cases of BCS were diagnosed on postmortem examination. MRI
      allows for noninvasive diagnosis by demonstrating characteristic changes which
      closely parallels the histopathological features of BCS. We report a case of 26
      year-old female with BCS involving bilateral thalami, with typical MRI
      appearance.

PMID- 21891942
TI  - Neuroplasticity in hemispheric syndrome: an interesting case report.
AB  - Functional hemispherectomy is an accepted treatment in hemispherical intractable
      epilepsy syndromes. We report a patient who had functional hemispherectomy for
      intractable seizures secondary to right hemispheric cortical dysplasia.
      Preoperatively, the patient had mild left hemiparesis and functional magnetic
      resonance imaging (fMRI) showed bilateral motor function lateralization to normal
      left hemisphere. The patient remains seizure free at 1-year follow-up, with no
      deterioration of motor power on left side. This report reviews physiology of
      neural plasticity for motor function lateralization and also reliability of fMRI
      in determining the functional shift.

PMID- 21891943
TI  - Epstein Barr virus encephalitis: clinical diversity and radiological similarity.
AB  - Clinico-radiological features of two patients with cerebrospinal fluid polymerase
      chain reaction-positive Epstein Barr virus (EBV) encephalitis have been reported.
      Both the patients presented with fever and altered sensorium, one had visual
      hallucination, decerebration followed by visual loss and the other had downward
      ocular deviation and orofacial and upper limb choreiform movement. Magnetic
      resonance imaging (MRI) revealed parieto-occipital involvement in both the
      patients. Follow-up MRI at one month was normal in one and revealed regression of
      lesion in the other. Both the patients, however, had severe neurologic sequelae
      at 18 months' follow-up. EBV encephalitis may have diverse clinical presentation
      with characteristic parieto-occipital involvement.

PMID- 21891944
TI  - Gamma knife treatment of an endolymphatic sac tumor: unique features of a case
      and review of the literature.
AB  - Endolymphatic sac tumors are rare, histologically non-aggressive lesions, but
      often become locally invasive and lead to erosion of the petrous bone. We report
      a rare case with multiple endolymphatic sac tumors located at bilateral
      cerebellopontine angles and vermis of the cerebellum. One of the lesions was
      surgically resected and others were treated using gamma knife radiosurgery. Local
      recurrence and metastasis occurred, which was treated with gamma knife
      radiosurgery. With an appropriate prescription dose and isodose, gamma knife
      radiosurgery may have an important role in the treatment of endolymphatic sac
      tumor.

PMID- 21891946
TI  - Delayed otogenic pneumocephalus complicating ventriculoperitoneal shunt.
AB  - Tension pneumocephalus complicating ventriculoperitoneal shunt is extremely rare.
      We report an elderly male who developed delayed tension pneumocephalus 12 months
      after ventriculoperitoneal shunt for hydrocephalus complicating aneurysmal
      subarachnoid hemorrhage. Fine-cut reformatted computer tomography scan revealed a
      large pneumatocele on the petrous apex associated with tegmen tympani defect. The
      shunt valve pressure was temporarily raised from 120 mm H 2 O to 200 mm H 2 O,
      and the patient underwent successful subtemporal extradural repair of the bony
      defect in the temporal bone. Although extremely rare, otogenic tension
      pneumocephalus is a potentially life-threatening condition, and urgent surgical
      repair of the bony defect in the temporal bone reduces the risk of both the
      morbidity and mortality.

PMID- 21891945
TI  - Utility of intraoperative fluorescent diagnosis of residual hemangioblastoma
      using 5-aminolevulinic acid.
AB  - Hemangioblastoma is a benign tumor of the cerebellum, and treatment involves
      surgical excision, both as the initial treatment and also in case of recurrence.
      Recurrence of hemangioblastoma can be local due to incomplete resection or can be
      distant and separate from the tumor resection region. Local recurrence can
      largely be avoided by verifying for any residual tumor intraoperatively before
      closure. In this study, we used intraoperative fluorescent diagnosis using 5
      aminolevulinic acid (5-ALA) to verify the presence of a residual tumor during
      surgical resection. Nine patients with hemangioblastoma were given 1 g of 5-ALA
      orally before surgery, and a laser beam of 405 nm was focused on the tumor during
      resective surgery. Fluorescence of protoporphyrin IX (PPIX) was observed in the
      core of tumor in all the cases. Fluorescence of PPIX was observed in the
      peritumoral cyst wall in two patients after tumor resection, and in both of them
      fluorescent parts of PPIX were resected and histological examination showed tumor
      cells. Usually, there are no tumor cells in the peritumoral cyst of a
      hemangioblastoma, yet hemangioblastomas may sometimes recur from an unresected
      cyst wall. It is thus necessary to excise an infiltrating cyst of tumor cells to
      prevent recurrence. Intraoperative fluorescent diagnosis using 5-ALA is a useful
      method to discern whether tumor cells are present in the peritumoral cyst wall of
      a hemangioblastoma.

PMID- 21891947
TI  - Delayed brain abscess after embolization of arterio-venous malformation: report
      of two cases and review of literature.
AB  - Infections of central nervous system are rare complications of endovascular
      procedures. Review of literature revealed only four reported cases of brain
      abscesses after embolization of intracranial arteriovenous malformations (AVMs).
      We report two new cases of delayed brain abscess after embolization of AVM. In
      one of the patients, it was due to an unusual organism, Burkholderia caeci.

PMID- 21891948
TI  - Chronic encapsulated intracerebral hematoma formation after radiosurgery for
      cerebral arteriovenous malformation.
AB  - We report a rare case of chronic encapsulated intracerebral hematoma (CEIH) after
      radiosurgery for a cerebral arteriovenous malformation (AVM). A 49-year-old male
      underwent transarterial embolization and surgical excision of a cerebral AVM
      presenting with cerebral hemorrhage in the left temporal lobe. Stereotactic
      radiosurgery (SRS) was done after 12 months. Magnetic resonance imaging (MRI) 14
      months after SRS showed a small-enhancing lesion close to the left lateral
      ventricle and marked white matter edema. At that time a diagnosis of radiation
      induced necrosis was made and steroids administered. At 43 months after SRS, MRI
      showed a small-enhancing mass close to the lateral ventricle with a hematoma
      cavity. Surgical excision was performed and histological examination revealed
      that the capsule consisted of an outer collagenous layer and an inner granulated
      layer with deposits of hemosiderin, which was compatible with CEIH. CEIH should
      be considered after SRS for AVM.

PMID- 21891949
TI  - Thoracic disc herniation with affection of the anterior spinothalamic tract: a
      case report and review of literature.

PMID- 21891950
TI  - Meningeal tuberculoma mimicking chloroma in a patient with chronic myeloid
      leukemia on imatinib.

PMID- 21891951
TI  - An unusual case of copper myelopathy.

PMID- 21891952
TI  - Reversible cerebellar ataxia: a rare presentation of depletional hyponatremia.

PMID- 21891953
TI  - Spontaneous intracranial hypotension in a patient with classical type Ehlers
      Danlos syndrome.

PMID- 21891954
TI  - Medulloblastoma with extreme nodularity.

PMID- 21891955
TI  - Anterior interhemispheric fissure meningioma without dural attachment in an
      adult.

PMID- 21891956
TI  - Human tail continuing as transitional lipoma.

PMID- 21891957
TI  - Hemorrhagic brain metastasis from osteogenic sarcoma of iliac bone in young
      female: unusual site of presentation.

PMID- 21891958
TI  - Massive subarachnoid pneumocephalus after a stereotactic brain biopsy.

PMID- 21891959
TI  - Non-awakening from anesthesia following posterior fossa surgery due to skull pin
      induced tension pneumocephalus.

PMID- 21891960
TI  - Calcification in vestibular schwannoma: report of two cases and review of the
      literature.

PMID- 21891961
TI  - Metastatic squamous cell carcinoma of the lung to the conus medullaris.

PMID- 21891962
TI  - Tracheal tube kinking during craniotomy in supine position after application of
      fish hook retractors.

PMID- 21891963
TI  - Primary thoracic primitive neuroectodermal tumor mimicking as neurofibroma.

PMID- 21891964
TI  - Pin site bilateral epidural hematoma - a rare complication of using Mayfield
      clamp in neurosurgery.

PMID- 21891965
TI  - Pan-meningiomatosis in an operated case of cerebellopontine angle meningioma.

PMID- 21891966
TI  - Thoracic epidural angiolipoma with extraspinal extension.

PMID- 21891967
TI  - Current state of symptomatic aortic valve stenosis in the elderly patient.

PMID- 21891968
TI  - Prognostic value of N-terminal pro-B-type natriuretic peptide in patients with
      acute coronary syndromes undergoing left main percutaneous coronary intervention.
AB  - BACKGROUND: Patients undergoing acute left main (LM) coronary artery
      revascularization have a high mortality and natriuretic peptides such as N
      terminal pro-B-type (NT-proBNP) have been shown to have prognostic value in
      patients with acute coronary syndromes. The present study looked at the
      prognostic value of NT-proBNP in these patients. METHODS AND RESULTS: We studied
      all consecutive patients undergoing acute LM coronary artery percutaneous
      coronary intervention between January 2005 and December 2008 in whom NT-proBNP
      was measured (n=71). We analyzed the clinical characteristics and the short- and
      long-term outcomes in relation to NT-proBNP level at admission. Median NT-proBNP
      was 1,364 ng/L, ranging from 46 to 70,000 ng/L. NT-proBNP was elevated in 63
      (89%) patients and was >=1,000ng/L in 42 (59%). Log NT-proBNP (hazard ratio [HR]
      3.51, 95% confidence interval [CI] 1.55-7.97, P=0.003) and left ventricular
      ejection fraction (HR 0.95, 95%CI 0.91-0.99, P=0.007) were predictors for all
      cause mortality. Log NT-proBNP was the only independent significant predictor of
      cardiovascular mortality. In-hospital mortality was 0% for patients with NT
      proBNP <1,000, but 17% for those with NT-proBNP >=1,000 (P=0.036). CONCLUSIONS:
      NT-proBNP is a strong predictor of outcome in patients undergoing acute LM
      coronary artery stenting. Mortality in such patients is high, but those with NT
      proBNP < 1,000ng/L may have a favorable short- and long-term prognosis. Further
      research, including a larger patient population, is needed to determine the
      optimal cut-off value for NT-proBNP in patients undergoing acute LM coronary
      artery intervention.

PMID- 21891969
TI  - Significant increase in the incidence of ventricular arrhythmic events after an
      intrathoracic impedance change measured with a cardiac resynchronization therapy
      defibrillator.
AB  - BACKGROUND: Cardiac resynchronization therapy defibrillator (CRT-D) devices are
      now capable of monitoring changes in intrathoracic impedance. Intrathoracic
      impedance monitoring resulting in a fluid index threshold crossing has been
      proven to predict heart failure (HF) exacerbations. We retrospectively
      investigated the relationship between changes in intrathoracic impedance and the
      occurrence of arrhythmic events. METHODS AND RESULTS: From 282 patients with New
      York Heart Association class III or IV HF who were implanted with a CRT-D device
      with a fluid index feature based on intrathoracic impedance monitoring
      capabilities, arrhythmic events were retrospectively analyzed in terms of the
      threshold crossings. The patients were divided into 2 groups: those with fluid
      index threshold crossings and those without threshold crossings. A total of 4,725
      tachyarrhythmic events were reported in 129 patients (46%), and there were 221
      fluid index crossing events in 145 patients (51%) during 10.0 +/- 3.2 months.
      Tachyarrhythmic events were more frequently recorded in patients with threshold
      crossing events than in those who did not experience a threshold crossing (3,241
      vs. 1,484 events, P<0.0001). Ventricular tachyarrhythmic events mainly occurred
      within the first 30 days after the threshold crossing event; however, a similar
      trend was not observed for the atrial tachyarrhythmic events. CONCLUSIONS:
      Intrathoracic impedance monitoring may predict arrhythmic events, especially
      ventricular arrhythmias, in patients with HF and provides an additional
      management tool.

PMID- 21891970
TI  - Serum level of fibrinogen Aalpha chain fragment increases in chronic
      thromboembolic pulmonary hypertension.
AB  - BACKGROUND: The cause of chronic thromboembolic pulmonary hypertension is unknown
      and there is no specific circulating biomarker for its detection. The aim of the
      present study was to use proteomic analysis to detect serum biomarkers by
      evaluating the serum profiles of low-molecular-weight peptides using matrix
      assisted laser desorption/ionization time-of-flight/time-of-flight mass
      spectrometry in patients with chronic thromboembolic pulmonary hypertension.
      METHODS AND RESULTS: Serum low-molecular-weight peptide profiling using the
      spectrophotometric technique was studied retrospectively in patients with chronic
      thromboembolic pulmonary hypertension and in controls matched for sex and age.
      The serum level of a 2989-Da peptide in the sera of patients was significantly
      higher compared to that of controls. Tandem mass spectrometry indicated that the
      peptide was a fragment of fibrinogen Aalpha chain (KMADEAGSEADHEGTHSTKRGHAKSRPV).
      The serum level of fibrinogen Aalpha chain fragment, measured using a heavy
      isotope internal standard, tended toward negative correlation with plasmin-alpha2
      plasmin inhibitor complex (P=0.073) and had a positive correlation with thrombin
      anti-thrombin complex (P=0.031). CONCLUSIONS: This fragment may be a potential
      diagnostic biomarker for chronic thromboembolic pulmonary hyper-tension.

PMID- 21891971
TI  - Prodrug approach in current drug discovery.

PMID- 21891972
TI  - Transient changes in thyroid functions tests after zoledronic acid infusion.
AB  - Zoledronic acid (ZA) induces an acute phase response in association with
      elevation of serum cytokines, which possibly alter the 3 types of iodothyronine
      deiodinase activity.  We therefore studied the possible alteration in thyroid
      function tests by ZA.  We investigated the acute changes in serum thyroid
      hormones, TSH, cortisol, white blood cells, CRP, interleukin-6 (IL-6) and tumor
      necrosis factor (TNF-alpha), before (0) and 1, 2 and 3 days after iv infusion of
      5 mg ZA in 24 asymptomatic postmenopausal women with osteoporosis (ZA group) in
      comparison with a placebo group.  In the majority of patients the ZA infusion was
      associated with acute phase response and fever within 24h after infusion which
      became attenuated on day three.  Concurrently with increase in serum cortisol,
      CRP, IL-6 and TNF-alpha, on day 1 and 2, total serum T3 (TT3), free T3  (fT3),
      total T4 (TT4) and fT4 decreased with a nadir on day 2 in association with an
      increase in the  fT4/fT3 ratio and reverse T3 (rT3) levels.  All thyroid function
      changes returned to the baseline levels on day 3, with cytokines still at higher
      levels, although lower than those on day 2.  Serum TSH remained essentially
      unchanged throughout the study.  The changes in thyroid hormones were at least in
      part explained by the increased TNF-alpha, but not by IL-6.  ZA induces short
      term changes in thyroid hormones, characteristic of nonthyroidal illness syndrome
      (NTIS), in association with an increase in TNF-alpha and IL-6.

PMID- 21891973
TI  - Binding of curcumin to senile plaques and cerebral amyloid angiopathy in the aged
      brain of various animals and to neurofibrillary tangles in Alzheimer's brain.
AB  - The binding of curcumin to senile plaques (SPs) and cerebral amyloid angiopathy
      (CAA) was examined in the aged brain of various animal species and a human
      patient with Alzheimer's disease (AD), together with its binding to
      neurofibrillary tangles (NFTs). Brain sections were immunostained with anti
      amyloid beta protein 1-42 (Abeta42) and anti-amyloid beta protein 1-40 (Abeta40)
      antibodies. These sections were also stained with alkaline Congo red, periodic
      acid-methenamine silver (PAM), and curcumin (0.009% curcumin solution) with or
      without formic acid pretreatment. The sections from the AD brain were also
      immunostained for anti-paired helical filament-tau (PHF-tau), and were stained
      with Gallyas silver for NFTs. Some SPs in the AD, monkey, dog, bear, and amyloid
      precursor protein transgenic mouse (APP Tg-mouse) brains contained congophilic
      materials, and were intensely positive for curcumin. In addition, curcumin
      labeled some diffuse SPs negative for Congo red in the AD, monkey, bear, and APP
      Tg-mouse brains. In all animals, CAA was intensely positive for both Congo red
      and curcumin. The specific curcumin staining activity was lost by formic acid
      pretreatment. In the AD brain, NFTs positive for PHF-tau and Gallyas silver were
      moderately stained with curcumin. These findings indicate that curcumin
      specifically binds to the aggregated Abeta molecules in various animals, and
      further to phosphorylated tau protein, probably according to its conformational
      nature.

PMID- 21891974
TI  - Physiological characterization of Campylobacter jejuni under cold stresses
      conditions: its potential for public threat.
AB  - Campylobacter jejuni is the major cause of human gastroenteritis worldwide. Under
      stress conditions, C. jejuni can enter a viable but non-culturable (VBNC) state.
      We found that the C. jejuni was able to enter a VBNC state by prolonged
      incubation at 4 degrees C. The standard isolation methods using pre-enrichment
      steps in Bolton broth or Preston broth could not detect the VBNC cells in spiked
      chicken meat. The transcription levels of virulence-associated genes (flaA, flaB,
      cadF, ciaB, cdtA, cdtB and cdtC) were expressed in VBNC cells but in low levels.
      The VBNC cells retained the ability to invade Caco-2 human intestinal epithelial
      cells in vitro. In most cases, VBNC cells failed to resuscitate in Caco-2 cells,
      but in some experiments, they formed colonies after co-incubation with host
      cells. Collectively, C. jejuni enters into a VBNC state at 4 degrees C and the
      VBNC C. jejuni remains virulent which may possibly lead to disease in humans. C.
      jejuni in VBNC state is a potential concern for food safety.

PMID- 21891975
TI  - Vitamin D status in cattle with malignant catarrhal fever.
AB  - The aim of the present study was to determine the vitamin D status in cattle with
      malignant catarrhal fever (MCF). Twelve cattle diagnosed as MCF and 6 healthy
      cattle (controls) were used in the study. Serum 1,25-dihydroxyvitamin D(3) (1,25
      D), 25-hydroxyvitamin D(3) (25-D), calcium, phosphorus and parathyroid hormone
      (PTH) levels were determined as 96.83 pg/ml, 30.0 ng/ml, 2.19 mmol/l, 1.57 mmol/l
      and 15.21 pg/ml in MCF group and 42.33 pg/ml, 37.0 ng/ml, 2.43 mmol/l, 1.96
      mmol/l and 36.08 pg/ml in controls, respectively. Although serum 1,25-D level in
      the MCF group was increased (P<0.01), serum calcium (P<0.01) and PTH (P<0.05)
      levels were decreased compared to the controls. The results suggest that there
      might be an interaction between vitamin D status and MCF.

PMID- 21891976
TI  - Nicotinamide prevents the down-regulation of MEK/ERK/p90RSK signaling cascade in
      brain ischemic injury.
AB  - Nicotinamide attenuates neuronal cell death related to focal cerebral ischemic
      injury. This study investigated whether nicotinamide exerts a neuroprotective
      effect through the activation of Raf- mitogen-activated protein kinase kinase
      (MEK)-ERK and its downstream targets, including p90 ribosomal S6 kinase (p90RSK)
      and Bad. Adult male Sprague-Dawley rats were treated with nicotinamide (500
      mg/kg) or vehicle 2 hr after the onset of middle cerebral artery occlusion
      (MCAO). Brains were collected 24 hr after MCAO. In the present study,
      nicotinamide significantly reduces the volume of infarct regions and decreases
      the number of positive cells by terminal deoxynucleotidyl transferase dUTP nick
      end labeling (TUNEL) staining in the cerebral cortex. Nicotinamide prevents
      injury-induced decrease in Raf-1, MEK1/2, and ERK1/2 phosphorylation. As part of
      the downstream cascade, nicotinamide inhibits the injury-induced decrease in
      p90RSK and Bad phosphorylation. Moreover, nicotinamide prevents the injury
      induced increase in cleaved caspase-3 levels. These findings suggest that
      nicotinamide protects neuronal cells against cerebral ischemic injury and that
      MEK-ERK-p90RSK cascade activation by nicotinamide contributes to these
      neuroprotective effects.

PMID- 21891977
TI  - Comparison of Campylobacter contamination levels on chicken carcasses between
      modern and traditional types of slaughtering facilities in Malaysia.
AB  - A total of 360 samples including fresh fecal droppings, neck skins, and swab
      samples was collected from 24 broiler flocks and processed by 12 modern
      processing plants in 6 states in Malaysia. Ninety samples from 10 traditional wet
      markets located in the same states as modern processing plants were also
      collected. Microbiological isolation for Campylobacter was performed following
      ISO 10272-1:2006 (E). The overall rate of contamination for Campylobacter in
      modern processing plants and in traditional wet markets was 61.1% (220/360) and
      85.6% (77/90), respectively. Campylobacter jejuni was detected as the majority
      with approximately 70% for both facilities. In the modern processing plants, the
      contamination rate for Campylobacter gradually declined from 80.6% before the
      inside-outside washing to 62.5% after inside-outside washing and to 38.9% after
      the post chilling step. The contamination rate for Campylobacter from processed
      chicken neck skin in traditional wet markets (93.3%) was significantly (P<0.01)
      higher than in modern processing plants (38.9%).

PMID- 21891978
TI  - [Tinea Corporis and Tinea Pedis].

PMID- 21891979
TI  - [Cryptococcosis].

PMID- 21891980
TI  - [The genus Aspergillus].

PMID- 21891981
TI  - [Cryptococcus].

PMID- 21891982
TI  - Sensitization to Bjerkandera adusta enhances severity of cough symptom in
      patients with fungus-associated chronic cough (FACC).
AB  - OBJECTIVE: The aim of the present study was to clarify the influence of
      sensitization to Bjerkandera adusta (B. adusta) on the clinical manifestation in
      patients with fungus-associated chronic cough (FACC). METHODS: Seventeen patients
      with FACC who underwent bronchoprovocation tests using an antigenic solution of
      B. adusta were selected from among 21 FACC patients. We compared the
      allergological findings and clinical characteristics of the FACC patients who
      showed a positive reaction to the bronchoprovocation test (Allergic fungal cough
      sensitized to B. adusta; AFC-Bj) with the remaining FACC patients (non AFC-Bj)
      retrospectively. RESULTS: The eleven patients with AFC-Bj had a median age of 52
      (range, 22-70) years, and 45.5% were female. The respective values for six
      patients with non AFC-Bj were 47.5 (range, 36-60) years of age, and 33.3% were
      female. The positive ratios for an immediate cutaneous reaction (45.5%; p<0.05)
      and the lymphocyte stimulation test (63.6%; p<0.05) to B. adusta were found to be
      significantly higher in the AFC-Bj group than in the non AFC-Bj group. The total
      time required for complete remission of cough symptoms was longer (median 20,
      range 12-43 weeks; p=0.0009), and the recurrence ratio of coughing was more
      frequent in the AFC-Bj group in comparison to those in non AFC-Bj group (2, range
      1-3 times and 0.5, range 0-1 times, respectively). CONCLUSIONS: This study
      demonstrated that B. adusta, a basidiomycetous is an environmental fungus
      attracting attention because of its possible role in enhancing the cough severity
      of FACC patients via the sensitization to this fungus.

PMID- 21891983
TI  - [Evaluation of antifungal effects of a traditional medicine containing 17
      components on Trichophyton verrucosum and Malassezia pachydermatis by
      microdilution].
AB  - The minimum inhibitory concentration(MIC)of a traditional medicine containing 17
      components against 9 strains of Trichophyton verrucosum and 13 strains of
      Malassezia pachydermatis was determined using a method recommended by the
      Clinical and Laboratory Standards Institute(CLSI). We also measured the MIC of
      each of the 17 components using the same method, and identified the main
      antifungal components.In order to evaluate MIC as a parameter of the antifungal
      effects using the microdilution method, we prepared 10% working solutions from
      10% (w/v)medicines. The geometric mean MIC of the medicinal extract against T.
      verrucosum was 2.51%, and that against M. pachydermatis was 2.25%. The components
      that exhibited antifungal effects were Rheum palmatum, Glycyrrhiza uralensis,
      Magnolia obovata, Phellodendron amurense, and Geranium thunbergii.

PMID- 21891984
TI  - Genetic relationship between Trichophyton mentagrophytes var. interdigitale and
      Arthroderma vanbreuseghemii.
AB  - Thirty-nine Arthroderma vanbreuseghemii isolates identified by mating behavior
      were assayed to determine their ribosomal RNA gene internal transcribed spacer
      (ITS) region genotypes. Twenty-two isolates of mating type (+) and 4 of (-)
      showed the genotype of Trichophyton mentagrophytes var. interdigitale, 9 isolates
      of mating type (+) and 4 of (-) showed the genotype of A. vanbreuseghemii. Nine
      of 14 isolates with granular or asteroid colony morphology showed the genotype of
      T. mentagrophytes var. interdigitale. There was no relation between ITS genotype
      and morphology or mating type of the isolates. Isolates of T. mentagrophytes var.
      interdigitale genotype were shown to include non-sexually degenerate zoophilic
      strains with granular colony morphology as well as sexually and morphologically
      degenerate anthropophilic strains and may be just one genotype of a heterogeneous
      species, A. vanbreuseghemii.

PMID- 21891985
TI  - [Study on the usefulness of rinse containing miconazole nitrate for treatment of
      dandruff--a double-blind, comparative study].
AB  - A double-blind, comparative study was performed on the usefulness of rinse
      containing miconazole nitrate(COFRM)compared to rinse without the reagent for the
      treatment of dandruff, when together with shampoo containing miconazole nitrate
      (COF). This study showed that both COFR and COFRM had about 80% utility. On the
      other hand, though it was not significant, enhanced improvement of itching by
      COFRM compared to COFR was detected 2 weeks after start of the examination. These
      results suggest that by mixing the miconazole nitrate with not only the shampoo
      but also rinse, the reagent more certainly remained on the scalp so that
      proliferation of the Malassezia was disturbed. Therefore, the effectiveness could
      clearly be more practically felt at the early stage. Collectively, these results
      indicate that COFRM was a useful rinse that allowed the effect to actually be
      felt in the short-term when used together with COF and contributed to the
      compliance improvement.

PMID- 21891986
TI  - [Case of primary cutaneous Aspergillus caldioustus infection caused by nerve
      block therapy].
AB  - We report a case of primary cutaneous Aspergillus caldioustus infection caused by
      nerve block therapy. A 67-year-old Japanese woman had been treated with oral
      predonisolon and tacrolimus for adult-onset Still disease and interstitial
      pneumonia. She presented with a 2-month-history of the lesions on the left back.
      A biopsy specimen from the skin lesion revealed granulomatous inflammation with
      hyphae. Culture of the pus and the skin specimen confirmed the diagnosis of
      cutaneous Aspergillus infection. The sequence of beta- tubulin gene was analyzed
      to confirm the mycological diagnosis and the causative agent was identified as A.
      caldioustus. The patient was treated with surgical removal of the lesions and
      oral 200 mg/day itraconazole but she died of infectious interstitial pneumonia
      due to Pneumocystis jiroveci and Cytomegalovirus infection Percutaneous infection
      may have been responsible for the incidence of localized infection. There was no
      evidence of systemic aspergillosis. A. caldioustus is an emerging opportunistic
      fungal pathogen in immunocompromised patients. Immunocompromised patients who
      have persistent traumatic atypical skin lesion need to be ruled out of such rare
      fungus infection. An opportunistic infection in Immunocompromised patients can be
      life-threatening and prompt treatment based on accurate diagnosis is important.

PMID- 21891987
TI  - Multiple gene analyses are necessary to understand accurate phylogenetic
      relationships among Trichophyton species.
AB  - Phylogenetic relationships among 34 isolates from 11 Trichophyton and 3
      Arthroderma species were investigated using the nucleotide sequences from 4 DNA
      regions: internal transcribed spacers (ITS) 1 and 2 including the 5.8S rRNA gene,
      and the actin (ACT), DNA topoisomerase (TOP) 2 and glyceraldehyde-3-phosphate
      dehydrogenase (GPD) genes. All four phylogenetic trees showed that the 34
      isolates can be divided into 3 clades, the Arthroderma simii, A. benhamiae and
      Trichophyton rubrum clades. The Shimodaira-Hasegawa test (SH test) revealed
      significant topological incongruities within the A. benhamiae and A. simii
      clades. Although branching patterns of the 3 clades were inconsistent among the
      four trees, the SH test did not support these differences except that the best
      tree topology according to ACT sequences was significantly rejected by the TOP
      data set. These results show that multiple gene analyses are necessary to more
      precisely understand the phylogenetic relationships among these fungi.

PMID- 21891988
TI  - [Chromoblastomycosis caused by Fonsecaea monophora].
AB  - Fonsecaea species are major etiologic agents of Chromoblastomycosis (CBM). By
      genetic analysis, the genus Fonsecaea has recently been revised and classified
      into F. pedorosoi, F. monophora and F. nubica. Here we report a severe chronic
      case of CBM caused by F. monophora. A 55-year-old Filipino male developed
      progressive skin lesions on the left lateral ankle in 1973, when he worked at a
      coconut plantation in the Philippines. In 1999, he received medical treatments
      for enlarged, multiple lesions on the left lower limb. When he moved to Japan in
      2005, the lesions were remarkably improved and he discontinued taking the
      medicine. On our first examination in October 2008, a large, reddish, cicatricial
      plaque was observed on the left lower aspect of his leg. Several tumorous lesions
      surrounded the plaque, indicating that the therapies performed before had been
      insufficient. In addition, there were many patchy scars scattered on the thigh
      and the upper part of the lower leg. The diagnosis of CBM was made by the
      presence of muriform cells. Black, pulverulent colonies were yielded in culture
      of skin scrapings and tissues. Although the fungus could not be identified by
      microscopic morphology, r-RNA ITS sequence analysis enabled identification of
      Fonsecaea monophora. The patient responded well to oral voriconazole combined
      with local thermotherapy using pocket warmers. The tumoral masses subsided in 6
      months, leaving pink scars with negative fungal culture. Voriconazole treatment
      was continued for 18 months. It seems that drugs are insufficiently delivered in
      the cicatricial lesions because of the paucity of blood flow, suggesting that a
      long-term follow-up is necessary for such a case.

PMID- 21891989
TI  - [Recent advances in the study of the Helicobacter pylori CagA oncoprotein].

PMID- 21891990
TI  - [New approach for prevention of gastric cancer].

PMID- 21891991
TI  - [Recent advance of chemotherapy in gastric cancer].

PMID- 21891992
TI  - [Current progress in gastric malignant lymphoma].

PMID- 21891993
TI  - [Infliximab-induced lupus erythematosus in a case of ulcerative colitis].
AB  - Infliximab is widely used in the treatment of inflammatory bowel disease, but
      despite its good clinical efficacy and tolerance, drug-induced autoimmune
      disorders have been reported as adverse reactions and are a matter of concern.
      Here we report a patient with ulcerative colitis who developed drug-induced lupus
      erythematosus after infliximab treatment. While this is a rare complication of
      infliximab, early diagnosis and successful management are essential.

PMID- 21891994
TI  - [Ileocecal resection for idiopathic intussusception in an adult].
AB  - A 60-year-old woman presented with abdominal pain and bloody stools. On
      examination, there was muscular guarding and rebound tenderness in the right
      abdomen. Abdominal ultrasonography and CT showed a concentric structure in the
      ascending colon and ascites. Emergency surgery was performed with a preoperative
      diagnosis of idiopathic intussusception. At operation, an intussusception was not
      seen, but ileocecal resection was performed to remove a possible tumor. No lesion
      that could have caused intussusception was identified in the resected bowel
      segment, so the condition was idiopathic.

PMID- 21891995
TI  - [A case of ampullary cancer with pancreas divisum treated by endoscopic
      papillectomy].
AB  - A 60's man underwent a medical check-up and esophagogastroduodenoscopy revealed
      an exposed-type tumor at the ampulla of Vater. Endoscopic ultrasonography and
      intraductal ultrasonography showed a hypoechoic mass limited to the ampulla of
      Vater. Endoscopic retrograde cholangiopancreatography (ERCP) revealed a slightly
      dilated ventral pancreatic duct not connected to the dorsal duct. Endoscopic
      papillectomy was performed without pancreatic stent placement and his
      postprocedural course was uneventful. The specimen was histologically diagnosed
      as well-differentiated adenocarcinoma limited to the mucosa of the ampulla of
      Vater. Endoscopic papillectomy without pancreatic stent placement can be
      performed without a risk of post-ERCP pancreatitis for ampullary tumor limited to
      the mucosa of the ampulla of Vater associated with pancreas divisum.

PMID- 21891996
TI  - [Two cases of ileocecal carcinoid found by total colonoscopy and a review of the
      literature on 16 cases].
AB  - We report 2 cases of ileocecal carcinoid with review of the literature recently
      reported in Japan. Both cases were diagnosed as carcinoid by colonoscopic biopsy
      after ileocecal tumors had been pointed out by computed tomography. We performed
      curative operation with lymph node dissection. Since multiple lymph node
      metastases were shown in both cases pathologically, they were closely followed
      after surgery, but no recurrence has been shown. Since SSTR2a stain was strongly
      positive in both cases, octreotide, the effectiveness of which was verified in
      the PROMID study might be administered if necessary. As ileocecal carcinoid has a
      tendency to metastasize to other organs, careful surveillance by colonoscopy and
      early detection are required. Furthermore, development of effective drugs
      following octreotide and further investigation including biological and
      histopathological analysis of neuroendocrine tumors including carcinoid are
      necessary.

PMID- 21891997
TI  - [A case of true diverticulosis of the appendix with intussusception].
AB  - A 50-year-old woman who was given a diagnosis of acute appendicitis was referred
      to our hospital. Because an abdominal enhanced CT revealed a dilated and cystic
      lesion in the appendix, operation was performed under the diagnosis of the
      suspicion of acute appendicitis or appendiceal mucocele. We performed
      laparoscopic cecal resection because of the intraoperative diagnosis of
      intussusception of the appendix. On the resected specimen, an elevated lesion was
      identified near the base of appendix. Histopathologically it was shown to be a
      true diverticulum in which the proper muscle layer are intact. To the best of our
      knowledge, this is the first report of true diverticulosis of the appendix with
      intussusception in the Japanese literature.

PMID- 21891998
TI  - [Autoimmune hemolytic anemia in a case of chronic hepatitis type C 56 weeks after
      initiation of second line treatment with pegylated interferon alpha2b/ribavirin
      combination therapy].
AB  - A 49-year-old man with chronic type C hepatitis had agreed to undergo pegylated
      interferon alpha2b/ribavirin (RBV) combination therapy during 48 weeks, but his
      hepatitis relapsed. Despite of second line treatment with the same combination,
      56 weeks later, his hemoglobin decreased and the dose of RBV was decreased. He
      was then admitted to our hospital because of increasing anemia and this
      combination therapy was stopped. The results of blood chemistry and immunological
      examination revealed he had contracted autoimmune hemolytic anemia (AIHA). In
      cases of deterioration of anemia during this combination, we must discuss about
      not only RBV-induced hemolytic anemia but also AIHA.

PMID- 21891999
TI  - [A case of metachronous invasive ductal carcinoma concomitant with intraductal
      papillary-mucinous neoplasm (IPMN) of the pancreas, which could not be detected
      in contrast-enhanced CT scan performed 3 months ago].
AB  - A 61-year-old man had been followed up in another hospital under diagnosis of
      branch duct type IPMN for 4 years. Contrast-enhanced CT scan for regular check
      performed 3 months ago revealed no increase of IPMN and no pancreatic tumor.
      However, he complained of back pain after that, MRI was performed. It revealed a
      solid tumor in size of 25mm diameter at the head of pancreas. The tumor was
      apparent from IPMN in several imaging modalities. Pancreatoduodenectomy was
      performed under diagnosis of invasive ductal carcinoma concomitant with IPMN.
      Post-operative pathological findings revealed IPMN was adenoma with mild atypia,
      and solid tumor was diagnosed invasive ductal carcinoma with solitary minute
      liver metastasis.

PMID- 21892000
TI  - [Annular pancreas with high confluence of pancreaticobiliary ducts in an adult].
AB  - A man in his 80's was admitted complaining of epigastralgia, and acute
      pancreatitis was diagnosed. Abdominal CT and MRI showed enlargement of the
      pancreatic head encircling the descending part of the duodenum and a duodenal
      diverticulum. Endoscopic retrograde cholangio-pancreatography (ERCP) revealed
      annular pancreas and high confluence of pancreaticobiliary ducts. Annular
      pancreas had been reported to have associated with a broad spectrum of pancreatic
      anomalies, few cases of annular pancreas coexisting with high confluence of
      pancreaticobiliary ducts, or pancreaticobiliary maljunction have been reported.
      Combination of both anomalies was interesting from the view point of embryology.
      We report a rare case of annular pancreas with high confluence of
      pancreaticobiliary ducts.

PMID- 21892001
TI  - Clinical characteristics of seven patients with Aeromonas septicemia in a
      Japanese hospital.
AB  - The genus Aeromonas comprises flagellated gram-negative rods widely distributed
      in freshwater, estuarine and marine environments. Aeromonas species may cause a
      variety of illnesses in humans, such as enterocolitis and septicemia, especially
      in warmer tropical or subtropical environments. To recognize the characteristics
      of Aeromonas septicemia in Japan, we reviewed laboratory data and medical records
      in our hospital. During 11 years (from 2000 to 2010), Aeromonas septicemia was
      observed in seven patients involving six female subjects. Six patients were
      observed in summer or fall. The incidence of Aeromonas septicemia was about 0.07
      per 1000 admissions, and two out of the seven patients died. All patients had
      underlying diseases such as malignancy (six patients) and choledocholithiasis
      (one patient). Two patients developed septicemia within two days after ingesting
      raw seafood. Five patients developed Aeromonas septicemia > 48 h after admission.
      Fever was present in all patients, and four out of the seven patients developed
      septic shock. All patients developed monomicrobial septicemia. A. hydrophila was
      isolated from five patients, and A. caviae and A. veronii biovar sobria were
      isolated from one patient each. Most antimicrobial agents had high activity
      against the isolated strains. However, a carbapenem-resistant strain appeared in
      one patient during treatment and led to death. Aeromonas septicemia is uncommon
      in temperate areas but can occur particularly in warm seasons. Immunocompromised
      conditions and recent ingestion of raw fish or shellfish are important
      characteristics of developing Aeromonas septicemia.

PMID- 21892002
TI  - Prenatal diagnosis of sirenomelia in the late second trimester with three
      dimensional helical computed tomography.
AB  - Sirenomelia is a rare congenital syndrome that is characterized by the anomalous
      development of the caudal region of the body. The anomalies include bilateral
      renal agenesis or dysgenesis and the absence of the sacrum and other vertebral
      defects. Sirenomelia is also known as "mermaid syndrome," because of the one
      lower extremity. It is usually associated with severe oligohydramnios, and its
      prognosis is very poor due to pulmonary hypoplasia that is caused by severe
      oligohydramnios. The patient referred to our hospital at the gestational age of
      27 weeks with fetal growth restriction and oligohydramnios. The estimated fetal
      body weight was 970 g (-4.9 S.D.). We could identify only one-side extremities,
      and could not identify kidneys by ultrasound examination. Because a single lower
      extremity and severe oligohydramnios are characteristics of the sirenomelia, we
      suspected sirenomelia. However, it could not be confirmed by ultrasound
      examination because of oligohydramnios. Therefore, we performed three-dimensional
      helical computed tomography (3D-CT), which is more accurate than ultrasound
      examinations for prenatal diagnosis of skeletal abnormalities. 3D-CT revealed an
      only one lower extremity. At 36 weeks and 5 days of gestation, the woman went
      into spontaneous labor and delivered an infant weighing 870 g. The infant has a
      single upper extremity and a single lower extremity. We provided supportive care
      for the neonate, who however died 1 hour 36 minutes after birth from severe
      respiratory distress. In summary, we report the correct diagnosis of sirenomelia
      with 3D-CT in the late second trimester.

PMID- 21892003
TI  - Single nucleotide polymorphisms of ABCC5 and ABCG1 transporter genes correlate to
      irinotecan-associated gastrointestinal toxicity in colorectal cancer patients: a
      DMET microarray profiling study.
AB  - Recent findings have disclosed the role of UDP-glucuronosyltransferase (UGT)
      1A1*28 on the haematological toxicity induced by irinotecan (CPT-11), a drug
      commonly used in the treatment of metastatic colorectal cancer (mCRC). We
      investigated the pharmacogenomic profile of irinotecan-induced gastrointestinal
      (GI) toxicity by the novel drug-metabolizing enzyme and transporter (DMET)
      microarray genotyping platform. Twenty-six mCRC patients who had undergone to
      irinotecan-based chemotherapy were enrolled in a case (patients experiencing >=
      grade 3 gastrointestinal, (GI) toxicity) - control (matched patients without GI
      toxicity) study. A statistically significant difference of SNP genotype
      distribution was found in the case versus control group. The homozygous genotype
      C/C in the (rs562) ABCC5 gene occurred in 6/9 patients with GI toxicity versus
      1/17 patients without GI toxicity (P=0.0022). The homozygous genotype G/G in the
      (rs425215) ABCG1 was found in 7/9 patients with GI toxicity versus 4/17 patients
      without GI toxicity (P=0.0135). The heterozygous genotype G/A in the 388G>A
      (rs2306283) OATP1B1/SLCO1B1 was found in 3/9 patients with grade >= 3 GI toxicity
      vs. 14/17 patients without GI toxicity (P=0.0277). DNA extracted from peripheral
      blood cells was genotyped by DMET Plus chip on Affymetrix array system. Genotype
      association was calculated by Fisher's exact test (two tailed) and relevant SNPs
      were further analyzed by direct sequencing. We have identified 3 SNPs mapping in
      ABCG1, ABCC5 and OATP1B1/SLCO1B1 transporter genes associated with GI toxicity
      induced by irinotecan in mCRC patients expanding the available knowledge of
      irinogenomics. The DMET microarray platform is an emerging technology for easy
      identification of new genetic variants for personalized medicine.

PMID- 21892004
TI  - The use of Streptomyces for immunization against mycobacterial infections.
AB  - Tuberculosis is one of the leading causes of mortality produced by an infectious
      agent. Different strategies including bioinformatics are currently being tested
      to identify and improve vaccines against tuberculosis. Comparative genome
      analysis between Streptomyces coelicolor and Mycobacterium tuberculosis suggest
      that both descend from a common Actinomycete ancestor. In this work, we suggest
      the use of Streptomyces as a live vector and explore the capacity of Streptomyces
      immunization to induce a protective response against mycobacterial infection.
      First, we compared the theoretical proteomes of S. coelicolor A3(2) with those of
      M. tuberculosis H37Rv and Mycobacterium bovis AF2122/97. This study showed a high
      similarity at the level of individual genes sequences with both bacteria sharing
      several membrane proteins. Then, we administered Streptomyces intraperitoneally
      to mice and determined its distribution by histopathology and culture; we did not
      find systemic dissemination. After administration of Streptomyces through
      different routes, we identified the most immunogenic, inducing strong humoral
      response, as denoted by the high serum antibody titers against this organism with
      cross reactivity to mycobacterial antigens. Finally, we evaluated the level of
      protection elicited by the inoculation of Streptomyces in Balb/c mice challenged
      with BCG. In these animals, lung bacillary loads were significantly lower than
      the control non-sensitized group.. These observations, along with Streptomyces'
      potential for expressing foreign proteins, suggest that Streptomyces could be an
      advantageous vector in the design of new tuberculosis vaccines.

PMID- 21892005
TI  - Persistence of immune response to HPV-16/18 AS04-adjuvanted cervical cancer
      vaccine in women aged 15-55 years.
AB  - The HPV-16/18 AS04-adjuvanted vaccine (Cervarix(r), GlaxoSmithKline Biologicals)
      has been shown to induce a robust immune response in women aged 15-55 years
      (103514/NCT00196937). This follow-up study is the first report of persistence of
      immune response and safety profile through 48 months after vaccination in women
      aged 15-55 years. In this open-label, age-stratified Phase III study in Germany
      and Poland (105882/NCT00196937), healthy women aged 15-55 years received 3 doses
      of HPV-16/18 AS04-adjuvanted vaccine at 0, 1, and 6 months. Anti-HPV-16/18
      seropositivity rates and geometric mean antibody titers (GMTs) were assessed by
      enzyme-linked immunosorbent assay (ELISA) in women aged 15-25 (n=168), 26-45
      (n=186) and 46-55 years (n=177) from the time of first vaccination through 48
      months. At Month 48, all subjects were seropositive for anti-HPV-16 antibodies
      and 99.4% were seropositive for anti-HPV-18. Antibody kinetics were as previously
      reported, with peak response at Month 7 followed by a gradual decline tending
      towards a plateau in all age groups. Anti-HPV-16/18 GMTs were sustained at Month
      48 in all age groups, including women aged 46-55 years in whom GMTs were
      respectively 11-fold and 5-fold higher than natural infection levels. The vaccine
      exhibited a clinically acceptable safety profile in all age groups. In summary,
      the HPV-16/18 AS04-adjuvanted vaccine induces high and sustained immune responses
      in women aged 15-55 years, with antibody levels remaining several-fold higher
      than natural infection levels for at least 4 years after the first vaccine dose.

PMID- 21892006
TI  - Anti-HBs antibody persistence following primary vaccination with an
      investigational AS02(v)-adjuvanted hepatitis B vaccine in patients with renal
      insufficiency.
AB  - BACKGROUND: Three doses of the investigational AS02(v)-adjuvanted hepatitis B
      virus (HBV) vaccine HB-AS02 have been shown to induce more rapid seroprotection
      and higher anti-HBs antibody concentrations in patients with renal insufficiency
      than four doses of FENDrixTM (HB-AS04), an adjuvanted HBV vaccine licensed in
      Europe for use in this population. This study evaluated persistence of immune
      response up to 36 months after primary vaccination. METHODS: In this open,
      international, Phase III follow-up study, 151 pre-dialysis, peritoneal dialysis
      and hemodialysis patients >=15 years of age received HB-AS02 at 0, 1, 6 months
      and 149 received HB-AS04 at 0, 1, 2, 6 months. Of these, 99 and 80 returned at
      Month 36, 76 and 62 of whom were eligible for inclusion in the Long-Term
      According-To-Protocol (LT-ATP) cohort for descriptive analysis of antibody
      persistence (mean age: 65.6 years). RESULTS: At Month 36, 89.5% of subjects in
      the HB-AS02 group and 72.6% of those in the HB-AS04 group had anti-HBs antibody
      concentrations >=10 mIU/ml. Anti-HBs antibody concentrations were >=100 mIU/ml in
      82.9% and 35.5% of subjects, respectively. Anti-HBs geometric mean antibody
      concentrations were higher in the HB-AS02 group over the 36 months of follow-up.
      An exploratory "time to boost" analysis confirmed that subjects who received HB
      AS02 were 2.54 times more likely than those who received HB-AS04 to have anti-HBs
      antibody concentrations >=10 mIU/ml at Month 36 (p=0.013 [95% CI: 1.22, 5.31]).
      CONCLUSION: HB-AS02 candidate vaccine induces high and persistent anti-HBs
      antibody levels in pre-dialysis, peritoneal dialysis and hemodialysis patients,
      potentially reducing the need for booster doses in this population.

PMID- 21892008
TI  - Mucosally-targeted HIV-1 vaccines.

PMID- 21892007
TI  - The evaluation of the opinions and attitudes of healthcare personnel of the
      province Diyarbakir against influenza A (H1N1) and the vaccination.
AB  - In this study it was targeted aimed to evaluate the opinions and attitudes of
      healthcare personnel of the province Diyarbakir against Influenza A(H1N1) and the
      vaccination and to determine the undesired effects after the vaccination. In this
      descriptive study, 1691 healthcare personnel participated. The participants were
      asked about their opinions about being included in the risk group or not, status
      of advising and having Influenza A(H1N1) vaccination, reasons of having or not
      having the vaccination, their opinions and attitudes about the pandemic and
      influenza vaccine and the practices of the press and the Ministry of Health. Of
      participants, 49.6% stated that they advised pandemic influenza vaccination. Of
      the healthcare personnel, 35.3% stated that they had pandemic influenza vaccine.
      Age, sex, profession, having seasonal influenza vaccine , using Media and the
      Ministry of Health as a source of information were important factors for the
      status of advising and having Influenza A(H1N1)v vaccine. The healthcare
      personnel should be informed about the purpose and practices of protection
      programs. It might be suggested to use press, which is regarded as the most
      important communication media, in accordance with the conditions in order to
      achieve suitable risk communication with the society.

PMID- 21892011
TI  - From immunology to vaccinology: a journey of trial and error towards more
      rational design.

PMID- 21892013
TI  - Canadian Academy of Sport and Exercise Medicine position paper: abuse,
      harassment, and bullying in sport.

PMID- 21892012
TI  - Chk1 inhibition and Wee1 inhibition combine synergistically to impede cellular
      proliferation.
AB  - Inhibition of the checkpoint kinase Chk1, both as a monotherapy and in
      combination with DNA damaging cytotoxics, is a promising therapeutic approach for
      the treatment of a wide array of human cancers. However, much remains to be
      elucidated in regard to the patient populations that will respond best to a Chk1
      inhibitor and the optimal therapeutics to combine with a Chk1 inhibitor. In an
      effort to discover sensitizing mutations and novel combination strategies for
      Chk1 inhibition, an siRNA screen was performed in combination with the selective
      Chk1 inhibitor AR458323. This screen employed a custom made library of siRNAs
      targeting 195 genes, most of which are involved in cell-cycle control or DNA
      damage repair. One of the most prominent and consistent hits across runs of the
      screen performed in three different cancer cell lines was Wee1 kinase. MK-1775 is
      a small molecule inhibitor of Wee1 that is currently in early stage clinical
      trials. In confirmation of the results obtained from the siRNA screen, AR458323
      and MK-1775 synergistically inhibited proliferation in multiple cancer cell
      types. This antiproliferative effect correlated with a synergistic induction of
      apoptosis. In cellular mechanistic studies, the combination of the two molecules
      resulted in dramatic decreases in inhibitory phosphorylation of cyclin-dependent
      kinases, an increase in DNA damage, alterations in cell-cycle profile, and
      collapse of DNA synthesis. In conclusion, the clinical combination of a Chk1
      inhibitor and a Wee1 inhibitor holds promise as an effective treatment strategy
      for cancer.

PMID- 21892014
TI  - Attention deficit hyperactivity disorder and the athlete: an American Medical
      Society for Sports Medicine position statement.
AB  - Attention deficit hyperactivity disorder (ADHD) is an important issue for the
      physician taking care of athletes since ADHD is common in the athletic
      population, and comorbid issues affect athletes of all ages. The health care
      provider taking care of athletes should be familiar with making the diagnosis of
      ADHD, the management of ADHD, and how treatment medications impact exercise and
      performance. In this statement, the term "Team Physician" is used in reference to
      all healthcare providers that take care of athletes. These providers should
      understand the side effects of medications, regulatory issues regarding stimulant
      medications, and indications for additional testing. This position statement is
      not intended to be a comprehensive review of ADHD, but rather a directed review
      of the core issues related to the athlete with ADHD.

PMID- 21892015
TI  - Does cervical muscle strength in youth ice hockey players affect head impact
      biomechanics?
AB  - OBJECTIVE: To evaluate the effect of cervical muscle strength on head impact
      biomechanics. DESIGN: Prospective cohort. SETTING: Field setting. PARTICIPANTS:
      Thirty-seven volunteer ice hockey players (age = 15.0 +/- 1.0 years, height =
      173.5 +/- 6.2 cm, mass = 66.6 +/- 9.0 kg, playing experience = 2.9 +/- 3.7
      years). INTERVENTIONS: Participants were equipped with accelerometer-instrumented
      helmets to collect head impact biomechanics (linear and rotational acceleration)
      throughout an entire playing season. Before the season, isometric cervical muscle
      strength was measured for the anterior neck flexors, anterolateral neck flexors,
      cervical rotators, posterolateral neck extensors, and upper trapezius. Data were
      analyzed using random intercept general mixed linear models, with each individual
      player as a repeating factor/cluster. MAIN OUTCOME MEASURES: Dependent variables
      included linear and rotational head accelerations. Cervical strength data were
      categorized into tertiles, creating groups with high, moderate, and low strength.
      Strength measures were averaged and normalized to body mass. RESULTS: Significant
      differences in cervical muscle strength existed across our strength groups (P <
      0.05). No differences were observed in linear or rotational acceleration across
      strength groups for the anterior neck flexors (PLin = 0.399; PRot = 0.060),
      anterolateral neck flexors (PLin = 0.987; PRot = 0.579), cervical rotators (PLin
      = 0.136; PRot = 0.238), posterolateral neck extensors (PLin = 0.883; PRot =
      0.101), or upper trapezius (PLin = 0.892; PRot = 0.689). CONCLUSIONS: Our
      hypothesis that players with greater static neck strength would experience lower
      resultant head accelerations was not supported. This contradicts the notion that
      cervical muscle strength mitigates head impact acceleration. Because we evaluated
      cervical strength isometrically, future studies should consider dynamic (ie,
      isokinetic) methods in the context of head impact biomechanics.

PMID- 21892016
TI  - Web-based portrayal of platelet-rich plasma injections for orthopedic therapy.
AB  - OBJECTIVE: Previous studies on Internet sites indicate that some Web-based
      material on sport-related orthopedic disorders is biased, misleading, and
      conveying inaccurate health messages. Our hypothesis was that Web-based content
      on platelet-rich plasma (PRP) therapy from commercial sites is frequently
      imbalanced, biased, and incorrect. DESIGN: In this descriptive epidemiological
      study, an Internet search was performed using the search engine Google using
      keywords "platelet-rich plasma" and "platelet-rich plasma therapy." Exclusion
      criteria were medical or scientific journal, encyclopedia, or medical reference
      articles. SETTING: Publicly available Internet resources were examined.
      PARTICIPANTS: Web-based resources identified through an Internet search engine.
      MAIN OUTCOMES MEASURES: Using content analysis, we assessed each reference for
      factual accuracy, themes depicted, opinions, and recommendations. RESULTS: Our
      search yielded a total of 44 articles, of which 26 unique articles met the
      inclusion criteria. Twenty of 26 articles (77%) made inappropriate statements
      regarding evidence, treatment, efficacy, or safety of PRP injections. Twenty
      three articles (88%) were medically imbalanced, discussing only perspectives of
      physicians favoring the treatment. Only 8 articles (31%) discussed alternative
      treatment options. Twenty-two articles (85%) used individual dramatized patient
      experiences to demonstrate the effectiveness of PRP. Nineteen articles (73%) made
      unsubstantiated promises regarding health outcomes of PRP injections. Many
      accessed Internet sites were from medical practices or institutions where PRP
      therapy was used. CONCLUSIONS: Our data indicate that some Web-based references
      to PRP therapy are biased and inaccurate. We are concerned that some readers will
      misinterpret such easily available, but poorly controlled, information,
      potentially leading to use of unproven therapies.

PMID- 21892017
TI  - The impact of ST elevation on athletic screening.
AB  - OBJECTIVE: To demonstrate the prevalence and patterns of ST elevation (STE) in
      ambulatory individuals and athletes and compare the clinical outcomes. DESIGN:
      Retrospective cohort study. ST elevation was measured by computer algorithm and
      defined as >=0.1 mV at the end of the QRS complex. Elevation was confirmed, and J
      waves and slurring were coded visually. SETTING: Veterans Affairs Palo Alto
      Health Care System and Stanford University varsity athlete screening evaluation.
      PATIENTS: Overall, 45 829 electrocardiograms (ECGs) were obtained from the
      clinical patient cohort and 658 ECGs from athletes. We excluded inpatients and
      those with ECG abnormalities, leaving 20 901 outpatients and 641 athletes.
      INTERVENTIONS: Electrocardiogram evaluation and follow-up for vital status. MAIN
      OUTCOME MEASURES: All-cause and cardiovascular mortality and cardiac events.
      RESULTS: ST elevation in the anterior and lateral leads was more prevalent in men
      and in African Americans and inversely related to age and resting heart rate.
      Athletes had a higher prevalence of early repolarization even when matched for
      age and gender with nonathletes. ST elevation greater than 0.2 mV (2 mm) was very
      unusual. ST elevation was not associated with cardiac death in the clinical
      population or with cardiac events or abnormal test results in the athletes.
      CONCLUSIONS: Early repolarization is not associated with cardiac death and has
      patterns that help distinguish it from STE associated with cardiac conditions,
      such as myocardial ischemia or injury, pericarditis, and the Brugada syndrome.

PMID- 21892018
TI  - The value of anterior inguinal exploration with local anesthesia for better
      diagnosis of chronic groin pain in soccer players.

PMID- 21892021
TI  - An hour of physical activity per day helps to keep weight gain at bay.

PMID- 21892020
TI  - In response to: is there evidence for mandating electrocardiogram as part of the
      pre-participation exam?

PMID- 21892022
TI  - Type of running shoe, individual footprint, and risk of injury in Marine Corps
      training.

PMID- 21892023
TI  - Does the addition of a corticosteroid injection to exercise therapy improve
      outcomes in subacromial impingement syndrome?

PMID- 21892024
TI  - Manual therapy and home exercise for chronic rotator cuff disease.

PMID- 21892025
TI  - Imaging of extranodal lymphoma with PET/CT.
AB  - Hodgkin disease (HD) and non-Hodgkin lymphoma (NHL) represent a spectrum of
      malignant neoplasms arising from the lymphoid system with an incidence of around
      8% of all malignancies. Although they are generally known as tumors of lymph
      nodes, 25% to 40% of HD/NHL tumors, especially NHL, arise at extranodal sites
      along the gastrointestinal tract, head and neck, orbit, central and peripheral
      nervous system, thorax, bone, skin, breast, testis, thyroid, and genitourinary
      tract. Extranodal involvement is an important pretreatment prognostic factor for
      patients with lymphoma and its incidence has increased in the past 2 decades.
      Imaging plays an important role in the noninvasive pretreatment assessment of
      patients with extranodal lymphoma. This involvement can be subtle and may be
      overlooked during computed tomography (CT). Positron emission tomography/CT
      (PET/CT) has evolved into an important imaging tool for evaluation of lymphomas,
      facilitating the detection of affected extranodal sites even when CT shows subtle
      or no obvious lesions. Familiarity with extranodal manifestations and suggestive
      PET/CT features in different sites is important for accurate evaluation of
      lymphoma. This article reviews the extranodal PET/CT imaging findings regarding
      HD and NHL.

PMID- 21892026
TI  - Progressive transformation of germinal centers in a pediatric patient: initial
      evaluation and follow-up with serial F-18 FDG PET/CT imaging.

PMID- 21892027
TI  - Huge tumor thrombus of chondrosarcoma on FDG PET/CT.

PMID- 21892028
TI  - F-18 fluoride PET/CT in the detection of radiation-induced pelvic insufficiency
      fractures.

PMID- 21892029
TI  - Stress fracture of the first metatarsal in a fencer: typical appearance on bone
      scan and pinhole imaging.

PMID- 21892030
TI  - Bilateral cutaneous diffuse large B-cell lymphoma on FDG PET/CT.

PMID- 21892031
TI  - Dynamic O-(2-[18F]fluoroethyl)-L-tyrosine (F-18 FET) PET for glioma grading:
      assessment of individual probability of malignancy.
AB  - PURPOSE: (1) To investigate the diagnostic value of some O-(2-[F]fluoroethyl)-L
      tyrosine (F-18 FET) indices derived from the dynamic acquisition to differentiate
      low-grade gliomas from high-grade; (2) to analyze the course of tumor time
      activity curves (TACs); and (3) to calculate the individual probability of a high
      grade glioma using the logistic regression. METHODS: Seventeen low-grade (WHO I
      II) and 15 high-grade (WHO III-IV) gliomas were studied with dynamic F-18 FET
      PET. Regions of interests were drawn over the tumor and contralateral brain, and
      TACs were analyzed. We considered early standardized uptake value (SUV), middle
      SUV, late SUV, early-to-middle SUV tumor ratio, early-to-late SUV tumor ratio;
      time to peak (Tpeak), in minutes, from the beginning of the dynamic acquisition
      up to the maximum SUV of the tumor; and SoD (sum of the frame-to-frame
      differences). To assess the individual probability of high-grade, logistic
      regression was also used. RESULTS: High-grade gliomas showed significantly (P <
      0.0001) higher values when compared with low-grade gliomas in early SUV, early-to
      middle ratio, early-to-late ratio, Tpeak, and SoD. For the grading of gliomas,
      the best indices were early-to-middle ratio and Tpeak providing a diagnostic
      accuracy of 94%. TACs analysis provided an 87% diagnostic accuracy. For
      individual high-grade diagnosis, the logistic regression provided 93%
      sensitivity, 100% specificity, and 97% accuracy. CONCLUSION: Early-to-middle SUV
      tumor ratio and Tpeak were the best indices for assessing the grading of gliomas.
      Since early-to-middle ratio derives from the first 35 minutes of the dynamic
      acquisition, the PET study could last half an hour instead of 1 hour. By logistic
      regression, it is possible to assess the individual probability of high-grade,
      useful for prognosis and treatment.

PMID- 21892032
TI  - Incidence and intensity of F-18 FDG uptake after vaccination with H1N1 vaccine.
AB  - OBJECTIVE: To analyze the effect of H1N1 influenza A virus vaccination in
      patients referred for staging or follow-up F-18 fluorodeoxyglucose (FDG) positron
      emission tomography/computed tomography (PET/CT) for different malignant tumors.
      METHOD AND MATERIALS: Medical history of all patients scheduled for FDG PET/CT
      during the national vaccination campaign against H1N1 was evaluated for recent
      vaccination. Site of injection and time between PET/CT and the date of
      vaccination (dTime) was determined. A difference in the maximum SUV between ipsi-
      and contralateral deltoid muscle or axillary lymph node of more than 0.5 was
      determined as positive reaction. The best cut-off dTime for still visible
      reaction was calculated. All patients with positive ipsilateral lymph node were
      clinically followed. Institutional Review Board approval was waived. RESULTS: Of
      269 patients, 58 (21.5%) were vaccinated for the H1N1 within 4 weeks prior to
      PET/CT (mean, 14.5 +/- 8.7 days). Of them, 17 (29.3%) patients had FDG-positive
      lymph nodes (mean SUV, 1.43 +/- 1.06), with a dTime range from 1 to 14 days. Only
      2 of them had no increased FDG uptake in the ipsilateral deltoid muscle. The area
      under the receiver operator characteristic curve revealed a strong relation
      between time delay (dTime) and axillary activity (AUC, 0.9; 95% confidence
      interval, 0.816-0.983) with a cutoff at 8 days (Youden Index). At follow-up
      (mean, 183 days; range, 173-196 days), no patient was found to have required
      treatment or signs of axillary lymphadenopathy. CONCLUSIONS: H1N1 vaccination can
      cause false-positive FDG PET/CT findings, when administered less than 14 days
      before the test, with the highest probability if the vaccination was administered
      less than 8 days ago. Increased FDG activity in the ipsilateral deltoid muscle is
      a key finding for accurate interpretation of increased FDG activity in axillary
      lymph nodes.

PMID- 21892033
TI  - F-18 FDG PET/CT contributes to more accurate detection of lymph nodal metastasis
      from actively proliferating esophageal squamous cell carcinoma.
AB  - PURPOSE: Evaluating the status of disease progression is critical for planning a
      therapeutic strategy for esophageal cancer. In this regard, F-18
      fluorodeoxyglucose-labeled positron emission tomography (PET) is one of the most
      useful diagnostic modalities. However, there is room to improve its diagnostic
      performance, such as distinguishing lymph nodal metastases from false positives.
      In this study, we examined the diagnostic accuracy of fluorodeoxyglucose PET
      accompanied by computed tomography imaging (PET/CT) to detect regional lymph
      nodal metastasis from esophageal squamous cell carcinoma (ESCC). METHODS: A total
      of 102 patients diagnosed as ESCC were subjected to this study. These patients
      had a preoperative PET/CT examination to evaluate the existence of metastasis.
      The values of maximum standardized uptake value (SUVmax) in primary tumors and in
      metastasized lymph nodes were measured to analyze their relationship with various
      clinicopathologic characteristics including the status of tumor cell
      proliferation, which was assessed by immunohistochemistry for Ki-67. RESULTS: The
      SUVmax of the primary tumor was positively correlated with tumor size and vessel
      invasion, and was positively related with the SUVmax of lymph nodal metastasis,
      especially in cases of poorly differentiated ESCC. The SUVmax of metastasized
      lymph nodes was higher in larger-sized metastasized lymph nodes, whereas the Ki
      labeling index of lymph nodal metastasis was positively related with the SUVmax
      per unit area (SUVmax/mm). The diagnostic accuracy of PET/CT (87.3%) was higher
      than that of conventional CT scans (78.4%). CONCLUSIONS: The improved diagnostic
      accuracy of PET/CT can be explained by its ability to detect actively progressive
      metastasis at an early phase regardless of size.

PMID- 21892034
TI  - Prediction of the outcome of definitive chemoradiation by decrease in F-18 FDG
      uptake in nonsurgical esophageal squamous cell cancer.
AB  - PURPOSE: To analyze the predictive value of fluorine-18 fluorodeoxyglucose (F-18
      FDG) uptake using positron emission tomography and computed tomography to assess
      the outcome of definitive chemoradiation in nonsurgical esophageal squamous cell
      carcinoma. MATERIALS AND METHODS: A retrospective review of 61 patients with
      clinical stage T1-4, N0/1, and M0 was performed. Chemoradiation included
      chemotherapy with fluorouracil plus cisplatin and irradiation with a total dose
      of 5600 to 6400 centigray (cGy). Positron emission tomography combined with
      computed tomography scans were acquired before and during the therapy. The
      correlation between a decrease in FDG uptake and 5-year progression-free survival
      (PFS) was analyzed by a receiver operating characteristic curve method to
      determine a cutoff value. A 5-year overall survival (OS), PFS, and cancer
      specific survival (CSS) were evaluated by Kaplan-Meier method. RESULTS: The mean
      of standardized uptake value decreased significantly during chemoradiation (P =
      0.001). Using 51% reduction of FDG uptake as a cutoff value provided a
      sensitivity of 76.9% and a specificity of 79.2% in predicting PFS (P = 0.000).
      The positive predictive value and negative predictive value were 50% and 95%,
      respectively. PFS, CSS, and OS were significantly different when grouped by this
      cutoff value (P < 0.05), and when dichotomized by stage T1-2 and T3-4 (P < 0.05),
      simultaneously with a decrease of 51% or more in FDG uptake. CONCLUSIONS: This
      study showed that a 51% decrease in FDG uptake during chemoradiation was a
      sensitive and accurate cut-point for predicting PFS. Stage T and decrease in FDG
      uptake were 2 independent predictive factors for 5-year PFS, CSS, and OS.

PMID- 21892035
TI  - Underperformance of gallium-67 scan is greater in relapse than in initial
      staging, compared with FDG PET.
AB  - PURPOSE: The purpose of this study is to evaluate the performance of gallium-67
      scan (GS) and F-18 fluorodeoxyglucose (FDG) PET scan in lymphoma staging and
      recurrence detection by comparing the 2 imaging studies in the same patient.
      MATERIALS AND METHODS: A total of 42 patients from the period between July 2002
      and May 2006 were included in this study. Of the 42 patients, 6 had Hodgkin
      disease and 36 had non-Hodgkin lymphomas. All of them underwent one or more FDG
      PET scans and also underwent corresponding GS performed within 7 days of FDG PET,
      for staging or detection of lymphoma recurrence. Among the non-Hodgkin lymphoma
      cases, 18 were diffuse large B-cell lymphoma, 10 were follicular center cell
      lymphoma, and 8 were of other types. Of the total 46 pairs of imaging performed
      in these 42 patients, 27 were for staging, and 19 for restaging after recurrence.
      RESULTS: In all these studies, FDG PET detected 230 lesion sites, whereas GS
      detected 85 lesion sites. All of the lesions detected by GS were noted on FDG
      PET, whereas GS detected only 37.0% of the lesions detected by FDG PET. Among the
      27 studies for staging, FDG PET detected 120 lesions, whereas GS detected 68
      lesions (56.7%). In the 19 images taken for relapse, FDG PET detected 110
      lesions, whereas GS detected only 17 (15.5%). CONCLUSIONS: FDG PET is superior to
      GS in staging and detecting all types of lymphoma. The difference is notably more
      significant in recurrence detection.

PMID- 21892036
TI  - Diagnostic performance of In-111 capromab pendetide SPECT/CT in localized and
      metastatic prostate cancer.
AB  - PURPOSE: To determine the diagnostic performance of In-111 capromab pendetide
      single photon emission computed tomography/computed tomography (SPECT/CT), in the
      prostate gland, seminal vesicles, and lymph nodes via correlation to a gold
      standard of histopathology. MATERIALS AND METHODS: In this study, we
      retrospectively reviewed all In-111 capromab pendetide SPECT/CT acquired at our
      institution for dedicated histopathology within a 4-month period. Statistical
      measures of performance were calculated in terms of glandular, seminal vesicle,
      and lymph node activity. The accuracies of glandular and seminal vesicle activity
      were then correlated to the indices of risk, including the stage, Gleason score,
      and prostate-specific antigen level, as well as the treatment history. RESULTS:
      Of the 200 scans meeting the criteria of our study, 197 had prostate gland
      histopathology, 94 had bilateral seminal vesicle histopathology, and 5 had a
      total of 43 resected lymph nodes for comparison. The overall accuracies of the
      scan results were determined to be 77.7% (area under the receiver operating
      characteristic curve [AUC] = 0.539) for the gland, 67.0% (AUC = 0.510) for the
      seminal vesicles, and 93.0% (AUC = 0.787) for lymph nodes. For glandular activity
      alone, scan accuracy was found to significantly improve with increasing Gleason
      score (P < 0.0001), and in a setting prior to treatment (P = 0.0005). No
      statistically significant differences were found between different scan groups
      with regards to seminal vesicle activity. CONCLUSIONS: The results of this study
      provide substantiating evidence In-111 capromab pendetide can be used to
      accurately diagnose lymph node metastases from primary cancers of the prostate;
      however, they also suggest the test may have limited utility in diagnosing tumors
      within the prostate gland and seminal vesicles.

PMID- 21892037
TI  - The value of F-18 FDG PET in patients with primary sclerosing cholangitis and
      cholangiocarcinoma using visual and semiquantitative analysis.
AB  - AIM: The aim of this study was to assess the value of 18F-fluorodeoxyglucose
      positron emission tomography (F-18 FDG PET) in patients with suspected
      cholangiocarcinoma (CC). METHODS: Sixty-five patients with suspected CC were
      included in this retrospective study. All patients had whole-body FDG PET/CT
      imaging at a mean time of 100 minutes after administration of FDG injection. PET
      studies were analyzed using visual analysis and semiquantitative analysis.
      Semiquantitative analysis was performed using maximum standardized uptake value
      (SUVmax) and tumor-to-normal liver (T/N) ratio. Malignancy was defined using the
      following criteria: (1) Visual analysis; (2) SUVmax >3.9; (3) T/N >1.6. Analysis
      of variance test and receiver operating characteristic analysis were used in
      statistical analysis. P < 0.05 was considered significant. RESULTS: Follow-up
      revealed 47 patients with CC. The average SUVmax in CC tumors was 8 +/- 2.9
      versus 3 +/- 1 in benign lesions (P < 0.0001). The average T/N in malignant
      lesions was 3.5 +/- 1.8 versus 1.3 +/- 0.4 in benign lesions (P < 0.0001).
      Sensitivity, specificity, and accuracy for the 3 criteria were as follows: (1)
      96%, 67%, and 88%; (2) 94%, 83%, and 91%; (3) 89%, 78%, and 86%. CONCLUSION: F-18
      FDG PET semiquantitative analysis using SUVmax >3.9 as criterion for malignancy
      could improve the diagnostic accuracy in differentiating malignant from benign
      lesions in patients with suspected CC.

PMID- 21892038
TI  - F-18 FDG PET/CT in rectal carcinoma: where are we now?
AB  - This short review aims at summarizing the available data pertaining to the
      usefulness of F-18 FDG PET/CT in rectal cancer. It is specifically focused on the
      emerging role of F-18 FDG PET/CT in assessing the response to neoadjuvant
      combined radiochemotherapy in locally advanced rectal cancer. It also probes the
      possibility of finding standardized PET/CT parameters that are capable of
      differentiating responders from nonresponders in whom therapeutic approach could
      be modified.

PMID- 21892039
TI  - Noninvasive and invasive staging of ovarian cancer: review of the literature.
AB  - The use of F-18 FDG PET/CT in the characterization of doubtful adnexal findings
      and in the staging of ovarian cancer is being extensively evaluated. The purpose
      of our article is to review the literature and to add our experience to the
      published works. We concluded that F-18 FDG PET/CT could represent an important
      method in addition to other imaging modalities (transvaginal ultrasound-, and
      contrast-enhanced computed tomography) in the characterization of adnexal masses
      and in the staging of ovarian cancer patients, particularly in assessing the
      presence of extra-abdominal metastatic spread.

PMID- 21892040
TI  - Preliminary study on the evaluation of olfactory neuroblastoma using PET/CT.
AB  - PURPOSE: Because of paucity of data available regarding the utility of PET/CT in
      the diagnosis and staging of patients with olfactory neuroblastoma (ONB), we
      retrospectively analyzed the efficacy of PET/CT in 9 patients with ONB. MATERIALS
      AND METHODS: Whole-body F-18 FDG PET/CT was performed in 7 patients with newly
      diagnosed ONB, as well as in 1 patient with recurrence and in 1 patient with
      remnant tumor. Regional C-11 choline (C-11 CHO) PET/CT was performed in 2
      patients with negative F-18 FDG scans. The lesion with intense radiotracer uptake
      was suggested as positive for tumor and the results of PET/CT were compared with
      conventional staging examinations. RESULTS: F-18 FDG PET/CT was positive in 7/9
      (77.7%) patients with ONB. In 2 patients with negative F-18 FDG, the lesions were
      C-11CHO avid. Both the primary tumors and its invasions were clearly delineated
      by F-18 FDG or C-11 CHO PET/CT. SUVmax of F-18 FDG in the primary tumor was 6.37
      +/- 4.22 and did not correlate with lesion size (F-18 FDG/size: r = 0.097, P =
      0.820). Whole-body F-18 FDG PET/CT detected parapharyngeal and cervical lymph
      node metastases in 2 patients, lung metastases in 1 patient, liver metastases in
      1 patients, and bone metastases in 2 patients. PET/CT altered the stages of 3 of
      9 patients with upstaging in 2 patients and downstaging in 1 patient.
      CONCLUSIONS: PET/CT may be useful for the diagnosis and staging of ONB.

PMID- 21892041
TI  - Radioiodine dilution due to levothyroxine when using recombinant human thyroid
      stimulating hormone: case report and discussion.
AB  - Following thyroidectomy, a patient with papillary thyroid carcinoma was found to
      have widespread radioiodine-avid metastatic lesions and was treated with I-131.
      When follow-up scanning was anticipated, his 24-hour urinary iodine was found to
      be 254 MUg. Because of the interim development of moderate renal failure, he was
      considered to be a candidate for preparation using recombinant human thyroid
      stimulating hormone (rhTSH), with continued administration of thyroid hormone. To
      decrease the dilution effect of nonradioactive iodine, levothyroxine was replaced
      with liothyronine, with a resultant decrease in 24-hour urinary iodine to less
      than 110 MUg, followed by radioiodine imaging, dosimetry, and retreatment with I
      131 for persistent, though improved disease. The dilution of radioiodine with
      nonradioactive iodine from any source may degrade image quality and reduce the
      effectiveness of therapy. The use of rhTSH has advantages in the evaluation and I
      131 treatment of differentiated thyroid cancer. There is evidence that this
      approach results in a longer effective half-time of radioiodine in remnants,
      improved bone marrow dosimetry, and comparable remnant ablation efficacy as
      compared with hormone withdrawal. However, it entails continued administration of
      thyroid hormone, which is a source of nonradioactive iodine. Reduction of the
      nonradioactive iodine burden of levothyroxine by conversion to liothyronine
      warrants investigation as possibly enhancing the advantages of rhTSH.

PMID- 21892042
TI  - Tips for leaders, part III: leadership during a time of change.
AB  - Good leaders anticipate the need for change and manage change well. However, the
      members of an organization generally oppose major change. There are many risks
      for the people and the group during a period of significant change. It is
      important that the leader communicates the reasons for the changes, involves as
      many people as possible in the process, develops a clear plan for implementation,
      and communicates well with the followers.

PMID- 21892043
TI  - Neurocutaneous melanosis: assessment on F-18 FDG and [11C]-methionine PET/CT and
      MRI.

PMID- 21892044
TI  - Ga-68-DOTA-NOC PET/CT reveals active Graves' orbitopathy in a single extraorbital
      muscle.

PMID- 21892045
TI  - Lesions of multiple myeloma adjacent to the skull are better visualized on F-18
      fluoroethyldimethyl-2-hydroxyethylammonium (FECH) PET images than on F-18 FDG PET
      images.

PMID- 21892047
TI  - A case of primary leptomeningeal melanoma evaluated on FDG PET/CT.

PMID- 21892046
TI  - Alveolar rhabdomyosarcoma with neuroendocrine differentiation detected by Ga-68
      DOTA-NOC PET/CT: a case report.

PMID- 21892048
TI  - Lung cancer metastasis to an adrenal myelolipoma detected by PET/CT.

PMID- 21892049
TI  - Sarcomatoid hepatocellular carcinoma diagnosed by FDG PET/CT.

PMID- 21892050
TI  - Hypertrophic osteoarthropathy seen with NaF18 PET/CT bone imaging.

PMID- 21892051
TI  - Rubidium-82 uptake in metastases from pheochromocytoma on PET myocardial
      perfusion images.

PMID- 21892052
TI  - F-18 FDG PET/CT findings of aggressive NK-cell leukemia.

PMID- 21892053
TI  - F-18 FDG PET/CT of a uterine smooth-muscle tumor of unknown malignant potential.

PMID- 21892054
TI  - Congenital triple kidney in a patient evaluated by F-18 FDG PET/CT for oncologic
      reason.

PMID- 21892055
TI  - PET appearance of tuberculous empyema necessitans.

PMID- 21892056
TI  - F-18 FDG PET/CT findings of huge cholesterol granuloma in multiple ribs.

PMID- 21892057
TI  - F-18 FDG PET/CT imaging of a hidradenocarcinoma of head and neck.

PMID- 21892058
TI  - Simultaneous rectal schwannoma and prostatic adenocarcinoma detected on FDG
      PET/CT.

PMID- 21892059
TI  - Mediastinal teratoma with metastatic lymph node: misleading normal thymic uptake
      of F-18 FDG.

PMID- 21892060
TI  - Fibrodysplasia ossificans progressiva detected on FDG PET/CT.

PMID- 21892061
TI  - Anthracotic solitary pulmonary nodule imitating lung malignancy on F-18 FDG
      PET/CT imaging.

PMID- 21892062
TI  - Incidental finding of multiple cavernous angiomas on FDG PET/CT.

PMID- 21892063
TI  - Absence of FDG uptake in a trauma patient with compromised vasculature as
      evidence of tissue nonviability.

PMID- 21892065
TI  - False positive F-18 FDG PET/CT in neck and mediastinum lymph nodes due to
      anthracosis in a buccal cancer patient.

PMID- 21892064
TI  - FDG PET/CT demonstration of pancreatic metastasis from prostate cancer.

PMID- 21892067
TI  - Current readings in nuclear medicine.

PMID- 21892066
TI  - Incidental finding of appendiceal tubular adenoma by F-18 FDG PET/CT.

PMID- 21892068
TI  - Pharmacotherapy and posttraumatic cephalalgia.

PMID- 21892070
TI  - Holy grail or false idol-and how to tell the difference.

PMID- 21892071
TI  - Ileal pouch microbial diversity.

PMID- 21892073
TI  - Is preoperative serum albumin enough to ensure nutritional status in the
      development of surgical site infection following gastrointestinal surgery?

PMID- 21892074
TI  - Prediction of posthepatectomy recurrence of hepatocellular carcinoma by
      circulating cancer stem cells: a prospective study.
AB  - OBJECTIVE: To investigate whether circulating cancer stem cells (CSCs) of
      hepatocellular carcinoma (HCC) can predict its recurrence after hepatectomy.
      BACKGROUND: HCC recurrence frequently occurs within the first year after
      hepatectomy, probably due to circulating tumor cells that have been shed from the
      primary tumor before hepatectomy. Because CSCs are more likely to initiate tumor
      growth than mature cancer cells, a high level of circulating CSCs may be a hint
      for HCC recurrence. METHODS: Multicolor flow cytometry was used to detect the
      number of circulating CSCs (CD45CD90CD44) in the peripheral circulation of 82 HCC
      patients 1 day before hepatectomy. The patients were monitored by CT or MRI for
      recurrence every 3 months. RESULTS: Forty-one (50%) patients had recurrence after
      a median follow-up period of 13.2 months (range, 1.3-57.1 months). Patients with
      recurrence had a higher median level of circulating CSCs than patients without
      recurrence (0.02% vs. 0.01%; P < 0.0001). Circulating CSCs > 0.01% predicted
      intrahepatic recurrence (relative risk 3.54; 95% CI, 1.41-8.88; P = 0.007) and
      extrahepatic recurrence (relative risk 10.15; 95% CI, 3-34.4; P = 0.0002).
      Patients with >0.01% circulating CSCs had a lower 2-year recurrence-free survival
      rate (22.7% vs. 64.2%; P < 0.0001) and overall survival rate (58.5% vs. 94.1%; P
      = 0.0005) than patients with <=0.01% circulating CSCs. On multivariable analysis,
      circulating CSCs > 0.01%, tumor stage and tumor size were independent factors
      predicting recurrence-free survival. CONCLUSIONS: Circulating CSCs predicted
      posthepatectomy HCC recurrence with high accuracy. They may be the target of
      eradication in the prevention of posthepatectomy HCC metastasis and recurrence.

PMID- 21892075
TI  - Probiotics and prebiotics in the management of irritable bowel syndrome:  a
      review of recent clinical trials and systematic reviews.
AB  - PURPOSE OF REVIEW: Irritable bowel syndrome (IBS) is a common disorder of the
      gastrointestinal tract, about which there has been considerable recent research.
      The aim of this article is to briefly review the aspects of IBS pathogenesis that
      involve the gastrointestinal microbiota, and then to critically appraise the
      recent and emerging evidence for the use of probiotics and prebiotics in its
      management. RECENT FINDINGS: The increased risk of developing IBS following
      gastroenteritis and the co-existence of dysbiosis, elevated luminal gas
      production and immune activation, indicate that the gastrointestinal microbiota
      may be a therapeutic target in IBS. Most systematic reviews indicate that
      probiotics have a beneficial impact on global IBS symptoms, abdominal pain and
      flatulence. However, recent trials indicate that different probiotics can
      improve, have no effect, or even worsen symptoms, confirming that benefits are
      likely to be strain and symptom-specific. There are no recent clinical trials of
      prebiotics in IBS, although previous studies indicate potential benefit at lower
      doses. SUMMARY: Clearly, some probiotics have considerable potential in the
      management of IBS; however, the benefits are likely to be strain-specific.
      Preliminary studies suggest low doses of prebiotics may improve symptoms of IBS,
      although further robust clinical trials are required.

PMID- 21892076
TI  - The thin-fat phenotype and global metabolic disease risk.
AB  - PURPOSE OF REVIEW: There has been a great deal of interest in the thin-fat
      phenotype evident in Asian Indians and its risk associations in the epidemic of
      noncommunicable chronic disease associated with it. The cause of this phenotype
      is probably related to lifestyle and environment; however, genotypic and
      epigenetic modifications in utero also have been considered. RECENT FINDINGS: The
      thin-fat phenotype occurs when fat is added to an already thin frame. This may
      occur with rural-urban migration, when positive energy balance occurs in a
      migrating population who were predominantly thin and physically active to begin
      with. The role of the pre-existing skeletal muscle mass and its interaction with
      newly deposited fat must be considered. The thin-fat phenotype may be programmed
      during fetal growth, but the evidence for this phenomenon is still not completely
      clear. Finally, although there is increased chronic disease morbidity at lower
      BMI and younger age in south Asian populations, BMI-related mortality does not
      appear to follow this trend. SUMMARY: At present, the weight of evidence appears
      to link the thin-fat phenotype to an environmental and lifestyle phenomenon
      occurring in previously thin people. This is particularly relevant in India,
      given the pace of transition over the last two decades.

PMID- 21892077
TI  - Update on micronutrients in bariatric surgery.
AB  - PURPOSE OF REVIEW: Obesity is a growing worldwide epidemic. Obese patients are
      often deficient in micronutrients despite macronutrient excess. Bariatric surgery
      is an increasingly utilized modality in the treatment of obesity and obesity
      related conditions. Bariatric surgery itself may cause or exacerbate
      micronutrient deficiencies with serious sequelae. This review will focus on
      perioperative strategies to detect, prevent and treat micronutrient deficiencies
      in patients undergoing bariatric surgery, and will highlight practical and
      clinical aspects of these nutritional problems. RECENT FINDINGS: Micronutrient
      deficiency is common in obese patients undergoing bariatric surgery both
      preoperatively and postoperatively. Bariatric procedures with a malabsorptive
      component are more likely to result in postoperative micronutrient deficiency. A
      system-based approach will facilitate clinical suspicion of specific or combined
      micronutrient deficiencies, leading to appropriate laboratory tests for
      confirmation. Supplementation by the oral route is always tried first, reserving
      parenteral administration for specific situations. SUMMARY: Clinicians should be
      aware that micronutrient deficiencies are common in obese patients who may have
      macronutrient excess. Micronutrient deficiency may exist preoperatively or be
      caused by bariatric procedures themselves. A systematic and team-based approach
      will decrease morbidity associated with delays in diagnosis and treatment.

PMID- 21892078
TI  - Iodine fortification:  why, when, what, how, and who?
AB  - PURPOSE OF REVIEW: To highlight current issues regarding the role of iodine
      fortification in correcting and preventing iodine deficiency. Universal salt
      iodization (USI) is recommended, wherein all salt is iodized; however, a more
      graduated approach may be warranted. RECENT FINDINGS: Iodine deficiency is
      widespread and has re-emerged in countries such as Australia, New Zealand and the
      UK. As well as supplementation in groups such as pregnant and lactating women who
      have increased iodine requirements, public health strategies to improve iodine
      intakes include voluntary or mandatory fortification of the food supply. A key
      player in the process of fortification is the food industry, wherein
      misperceptions that the addition of iodized salt to foods alters taste and colour
      still persist and legislation in some countries that prohibits its addition to
      manufactured foods, can result in a reluctance to support USI. SUMMARY:
      Ameliorating iodine deficiency on a population level in countries with mild-to
      moderate deficiency is warranted. Risk of both inadequate and excess iodine
      intakes requires regular monitoring to accompany fortification programmes as well
      as strategies to address subpopulations at risk. More sensitive indicators of
      recent iodine status are needed to rapidly assess the impact of fortification on
      improving the status.

PMID- 21892079
TI  - Impending therapies for Duchenne muscular dystrophy.
AB  - PURPOSE OF REVIEW: As the first genetic disease for which the culpable gene was
      identified by positional cloning, Duchenne muscular dystrophy has served as a
      paradigm for therapeutic approaches to neuromuscular disease, in which role it
      has proved especially testing. The large mass and broad distribution of the
      target tissue, skeletal muscle, have stretched the patience and ingenuity of
      those seeking therapeutic delivery of the largest known gene. The most promising
      recent advances are summarized in this article. RECENT FINDINGS: The main
      obstacle to genetic therapies has been the development of vectors able to
      efficiently deliver large, potentially therapeutic, genetic constructs to the
      large and widely dispersed mass of body musculature. Recombinant viral vectors
      that efficiently transduce muscle are unable to carry the full-length construct.
      Myogenic cells that are able both to carry full-length genes and to repair
      muscles are technically challenging to produce in sufficient quantity. A recent
      promising approach is the use of agents that obviate the mutation. SUMMARY:
      Although genetic and cell-mediated approaches are currently showing genuine
      promise in preclinical and clinical trials, there remains considerable interest
      in the development of agents that ameliorate the downstream pathology. One
      general challenge is the three-way tension between the interests of patients,
      regulators, and the biotechnology industry.

PMID- 21892080
TI  - Axonal Charcot-Marie-Tooth disease.
AB  - PURPOSE OF REVIEW: The aim is to specify the genetic causes of dominantly and
      recessively inherited axonal forms of Charcot-Marie-Tooth disease (CMT) and
      review the biological basis for these disorders. RECENT FINDINGS: More than 10
      genes that cause axonal CMT have been identified over the past decade. Many of
      these genes express proteins that are ubiquitously expressed. Clinical phenotypes
      of many of these disorders are being studied and animal and cellular models of
      these neuropathies have been created. SUMMARY: Identification of these new
      genetic causes of axonal neuropathy has not only been important for patients and
      their families but it has also provided exciting new information about disease
      mechanisms involved in neuronal degeneration. These mechanisms extend beyond the
      field of axonal CMT and have relevance to sensory neuropathies and motor neuron
      disorders. Therapeutic strategies for some of these are also provided. We hope
      that this review will be of interest to clinicians and scientists interested in
      axonal forms of CMT.

PMID- 21892081
TI  - Challenges in diagnosis and treatment of late-onset Pompe disease.
AB  - PURPOSE OF REVIEW: The first reports published in 2010 on enzyme replacement
      therapy in late-onset Pompe disease (LOPD) allow us now to stand back and adapt
      the strategies. In the meantime, substantial progress has been made in basic and
      applied research on animal models to enhance the efficacy of treatments. This
      brief review highlights the new concepts in a contemporary approach. RECENT
      FINDINGS: Interest in LOPD rose since its acknowledgement as a treatable
      myopathy. New insights from extensive analysis of injurious mechanisms resulted,
      over the past years, in the development of enzyme replacement therapy and a
      better understanding of its limits. SUMMARY: It seems reasonable to consider
      Pompe disease as a large spectrum of a single ubiquitous lysosomal disease
      resulting from an enzyme defect, more severe in newborns because of rapid
      cardiopulmonary and hepatic failures, with a much better prognosis when
      symptomatic after 12 months. This late-onset form demands therapy to avoid
      progressive motor disability and pulmonary insufficiency. Diagnosis is easy to
      confirm through rapid and reliable biochemical tests with sampling of blood dots
      on filter paper. When started early, treatment would avoid serious irrevocable
      damage to cells. Increasing precocity of diagnosis and efficacy of treatments are
      the core challenges for the next few years.

PMID- 21892082
TI  - Advances in acute lymphoblastic leukemia in adults.
AB  - PURPOSE OF REVIEW: This review will be focused on the advances in adult acute
      lymphoblastic leukemia (ALL) based on recently published articles. RECENT
      FINDINGS: Progress in the understanding of the molecular basis of ALL has
      contributed to a more precise definition of risk factors. The study of minimal
      residual disease has re-defined the baseline prognostic factors and has opened
      new strategies for postremission management. The use of pediatric-inspired
      therapies for young adults with standard-risk ALL, the broadening of the number
      of patients who are eligible for allogeneic stem cell transplantation, the
      increasing use of targeted therapies (monoclonal antibodies, tyrosine kinase
      inhibitors, and new purine analogs, etc.) in early phases of the disease,
      together with the improvements in supportive therapy explain the increased
      survival of young and middle-aged adult ALL. SUMMARY: These changes are improving
      long-term outcome, which in ongoing studies is expected to be of close to 50%,
      and are opening the door for future therapeutic advances.

PMID- 21892083
TI  - Advances in the understanding and management of primary myelofibrosis.
AB  - PURPOSE OF REVIEW: Identification of the JAK2V617F mutation in 2005 boosted basic
      and clinical research in primary myelofibrosis (PMF) and other Philadelphia
      negative chronic myeloproliferative neoplasms. We herein review the recent
      contributions to the understanding and management of PMF. RECENT FINDINGS: In
      addition to the JAK2V617F mutation, different genetic markers have recently been
      discovered in PMF, the most relevant ones being the mutations in the
      thrombopoietin (MPL), TET2, and EZH2 genes. From the clinical point of view,
      attention has recently been paid to thrombosis as a relevant complication of PMF
      and new prognostic models for this disease have been created and refined.
      Regarding therapy, reduced intensity conditioning regimens have allowed the
      possibility of performing allogeneic stem cell transplantation in older PMF
      patients, whereas the first clinical trials with JAK2 inhibitors have shown their
      efficacy in splenomegaly and constitutional symptoms. SUMMARY: The molecular
      biology of PMF is more complex than initially believed. Due to its associated
      mortality risk, stem cell transplantation should be restricted to patients with
      poor prognostic features. The JAK2-inhibitors are promising as a palliative
      treatment of PMF. In conclusion, the once neglected PMF has become a very active
      field of research, which will hopefully soon translate into relevant therapeutic
      advances.

PMID- 21892084
TI  - Signal transduction inhibitors in chronic lymphocytic leukemia.
AB  - PURPOSE OF REVIEW: Chronic lymphocytic leukemia (CLL) therapy has evolved over
      the past few decades as modern chemo-immunotherapy significantly improved the
      response and survival of CLL patients. However, treatment toxicity of the
      intensive chemo-immunotherapy often limits its use in the mostly elderly
      population of patients. Further, the disease eventually relapses and additional
      therapy options are required. Of particular interest are molecular targeted
      therapies that interfere with critical signal transduction pathways controlling
      cell growth and survival. This review will provide an update on the most recent
      preclinical and clinical development of signal transduction targeted therapy in
      CLL. RECENT FINDINGS: Small molecular kinase inhibitors have been developed to
      target the proximal B-cell receptor signaling pathway (e.g. spleen tyrosine
      kinase inhibitors and Bruton's tyrosine kinase inhibitors) or the downstream
      phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin pathway. These
      agents showed unique in-vitro activities by inducing apoptosis and blocking
      interaction of CLL cells and the protective microenvironment. They have also
      shown promising clinical activity in early-phase clinical studies and appear to
      alter lymphocyte trafficking. Inhibitors of the B-cell CLL/lymphoma 2 (BCL-2)
      family of antiapoptotic proteins and Cdk inhibitors are in active clinical
      development. Strategies modulating the CLL interaction with the microenvironment
      niche are emerging. Further understanding of novel signaling pathways helps to
      identify additional potential therapeutic targets. SUMMARY: Signal transduction
      inhibitors are promising new strategy for targeted CLL treatment. Identification
      of novel molecular targets and therapeutic agents will further expand our
      therapeutic options.

PMID- 21892085
TI  - Emerging roles for mammalian target of rapamycin inhibitors in the treatment of
      solid tumors and hematological malignancies.
AB  - PURPOSE OF REVIEW: The mammalian target of rapamycin (mTOR) is a key regulator of
      cell growth and survival in mammalian cells. mTOR pathways are frequently
      dysregulated in various malignancies, providing targets for new anticancer drugs
      and therapeutic strategies. Here, we summarize the clinical experience of trials
      using the first generation of mTOR inhibitors, the rapalogs, and highlight the
      development of the next generation of catalytic inhibitors of the pathway. RECENT
      FINDINGS: mTOR inhibitors have shown major clinical activity in the treatment of
      renal cell carcinoma and two rapalogs have been approved for treatment of this
      malignancy. Recently, clinically significant trials with these agents were
      conducted in mantle cell lymphoma, pancreatic neuroendocrine tumors and
      astrocytomas. There are also promising results emerging in sarcomas, breast
      cancer and lung carcinoma. Multiple agents targeting mTOR, belonging to the new
      class of catalytic inhibitors with activity against both mTORC1 and mTORC2, are
      currently in various stages of preclinical and clinical development. SUMMARY: The
      rapalogs are the first mTOR inhibitors to show promising, yet modest, antitumor
      effects. To fully exploit the potential of targeting this pathway, it will be
      important to better understand the mechanisms of action and precise targets of
      the various inhibitors. Moreover, definition of biomarkers of susceptibility and
      identification of predictors and/or correlates to drug resistance will
      substantially advance this area.

PMID- 21892086
TI  - Pediatric ependymomas:  will molecular biology change patient management?
AB  - PURPOSE OF REVIEW: Ependymomas remain a therapeutic challenge in pediatric neuro
      oncology. These tumors are chemoresistant and rather radioresistant and until
      recently little was known about their biology. RECENT FINDINGS: Histopathological
      grading of ependymomas according to the WHO classification is neither
      reproducible, nor correlated with outcome, especially in young children.
      Characterization of molecular abnormalities in ependymomas offers now a better
      understanding of their initiation and progression; different biological subtypes
      of tumors have been described and would need further validation. The
      identification of new prognostic biomarkers, such as tenascin-C overexpression or
      chromosome 1q gain, will considerably help patient stratification in future
      trials. Finally, the recent discovery of specific pathways involved in
      ependymomas oncogenesis, such as Notch-1or EPHB2 offers new perspectives for the
      development of targeted therapies. SUMMARY: A comprehensive biological work-out
      including CGHarray and immunohistochemistry for specific biomarkers should now be
      recommended for the current management of pediatric ependymoma, especially in
      young children if radiotherapy has to be omitted in the first line of treatment.

PMID- 21892087
TI  - Medulloblastomas:  update on a heterogeneous disease.
AB  - PURPOSE OF REVIEW: Medulloblastoma is the main primitive neuroectodermal tumour
      of the posterior fossa in childhood. The classical therapeutic approach consists
      of surgical resection, followed by craniospinal irradiation. Because of the good
      overall survival (75%), the main recent research efforts focus on refining the
      most relevant prognostic stratification and in decreasing the long-term sequelae.
      RECENT FINDINGS: Thanks to the better understanding of the heterogeneity of
      medulloblastomas, clinical, histological and biological markers have been clearly
      identified and allow risk-adapted strategies. A subset of tumours of early
      childhood (<3-5 years), frequently associated with a Sonic Hedgehog signalling,
      might be cured without irradiation. In older children, several trials have
      demonstrated the safety of reduced craniospinal irradiation in standard risk
      tumours. Furthermore, the evidence of an excellent prognosis associated with a
      subset of tumours characterized by an activation of the WNT pathway leads to
      forthcoming de-escalating strategies. Reducing long-term sequelae also relies on
      new surgical approaches aiming at reducing the cerebellar injuries. Tremendous
      efforts have also been made in defining the most adapted irradiation doses and
      fields. Intensity-modulated radiotherapy and proton beam therapy might also
      influence the long-term neurological and endocrine defects of the patients.
      SUMMARY: Histological and biological characteristics clearly define various
      prognostic groups within medulloblastomas; confirming the overall good outcome
      and reducing long-term sequelae are the main focus of current clinical trials.

PMID- 21892089
TI  - Letter commenting on "risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation
      carriers: experience with a consecutive series of 111 patients using a
      standardized surgical-pathological protocol" in Int J Gynecol Cancer 2011;21: 846
      851 by C. Bethan Powell et al.

PMID- 21892088
TI  - Comparative study of tamoxifen and raloxifene on endometrial cell proliferation
      of female rats in persistent estrus.
AB  - OBJECTIVE: The objective of the study was to compare the effect of tamoxifen and
      raloxifene on the endometrium of female rats in persistent estrus, by Ki-67
      protein expression. METHODS: The study comprised 60 Wistar-Hannover female rats
      in persistent estrus, induced by a single subcutaneous dose of 1.25 mg of
      testosterone propionate on the second day of age. At 90 days of life, the animals
      were randomly divided into 3 groups of 20 animals each. Group 1 (control),
      received only placebo; group 2, the animals were treated with tamoxifen, 250
      MUg/d; and group 3, the rats were treated with 750 MUg/d of raloxifene by gavage
      during 30 days. Then, the animals were killed, and the endometrium was removed
      for immunohistochemical analysis of Ki-67 antigen expression. Statistical
      analysis was performed by beta regression model (P < 0.05). RESULTS: Mean
      percentages of Ki-67 protein expression in the endometrium of rats in persistent
      estrus were 43.21% +/- 3.39%, 7.36% +/- 0.95%, and 7.20% +/- 0.76% in groups 1, 2
      and 3, respectively (P < 0.001). There was no statistical difference between
      groups 2 and 3 (P = 0.7159). CONCLUSIONS: The present results indicate that, at
      the doses and during the time of treatment used, both tamoxifen and raloxifene
      induce atrophy in a similar way of endometrial epithelium of rats in persistent
      estrus.

PMID- 21892090
TI  - Clinical significance of nucleostemin expression and its correlation with cyclin
      D1 expression in malignant ovarian tumors.
AB  - OBJECTIVE: To investigate the expression of the nucleostemin (NS) gene in ovarian
      tumors and its correlation with the expression of cyclin D1. METHODS: The
      expression levels of nucleostemin and cyclin D1 proteins were measured by
      immunohistochemical staining in ovarian tumors and normal ovarian tissues, and
      the relationship between their levels was analyzed. RESULTS: Nucleostemin gene
      and cyclin D1 expressions were detected in 28 and 27 specimens of malignant
      ovarian tumors (93.7% and 90.0%), 4 and 8 specimens of ovarian borderline tumors
      (40.0% and 80.0%), and in both specimens of benign ovarian tumors, respectively.
      The expression of NS gene was seen in 5, 13, and 10 specimens of malignant
      ovarian tumors of high, moderate, and low grade, respectively. The expression of
      the nucleostemin gene was significantly related to the tumor grade (r = 0.786, P
      < 0. 05), and a significant relationship between nucleostemin and cyclin D1
      expression was found (r = 0.834, P < 0.05). The expression of the nucleostemin
      gene was not detected in normal ovarian tissue. CONCLUSION: The expression of the
      nucleostemin gene in ovarian tumors is closely correlated with origination,
      progression, and grading of tumors and may serve as a marker in estimating the
      malignancy of ovarian tumors. The overexpression of cyclin D1 might be correlated
      with nucleostemin expression. Nucleostemin may have an impact on the passage of
      cells through the G1/S checkpoint, and thus cell cycle progress, by regulating
      cyclin D1 expression.

PMID- 21892091
TI  - Extended-field irradiation and intracavitary brachytherapy combined with
      cisplatin and amifostine for cervical cancer with positive para-aortic or high
      common iliac lymph nodes: results of arm II of Radiation Therapy Oncology Group
      (RTOG) 0116.
AB  - OBJECTIVES: Radiation Therapy Oncology Group (RTOG) 0116 was designed to test the
      ability of amifostine (Ethyol; MedImmune LLC, Gaithersburg, MD), a cytoprotective
      agent, to reduce the acute toxicity of combined therapy with extended-field
      irradiation, brachytherapy, and cisplatin chemotherapy in patients with cervical
      cancer with para-aortic or high common iliac disease. This report presents the
      results of part 2. MATERIALS AND METHODS: Radiation Therapy Oncology Group 0116
      was a 2-part trial. Part 1 delivered extended-field irradiation, brachytherapy,
      and cisplatin; part 2 added amifostine and required 16 evaluable patients to
      assess an improved toxicity profile. Eligibility included evidence for high
      common iliac or para-aortic metastasis. Patients were treated for a total dose of
      45 Gy in 25 fractions with intracavitary irradiation. Intensity-modulated
      radiation therapy was not allowed. The final point A dose was 85 Gy low-dose rate
      equivalent. High-dose rate techniques were allowed. The positive para-aortic and
      iliac nodes were to be boosted to 54 to 59.4 Gy. Amifostine at 500 mg was to be
      delivered with every fraction of radiotherapy. RESULTS: The study opened on
      August 1, 2001, and closed March 3, 2007, after accruing 45 patients, 18 for the
      second part with amifostine. This analysis reports the primary end point for the
      patients entered on part 2 of the study. Three patients were excluded, one was
      ineligible, and 2 withdrew. The median follow-up was 22.9 months (range, 6.5-45.4
      months). The median dose of amifostine delivered was 5000 mg (range, 500-13,500
      mg). Thirteen patients (87%) experienced an acute grade 3/4 toxicity (excluding
      grade 3 leukopenia). This compared to an 81% rate in part 1 of the trial. The
      estimated median survival was 34.8 months with a 20% late grade 3/4 toxicity
      rate. CONCLUSIONS: Amifostine, as delivered in this study, did not reduce acute
      toxicity in this patient population.

PMID- 21892092
TI  - Human papillomavirus genotype distribution and human papillomavirus 16 and human
      papillomavirus 18 genomic integration in invasive and in situ cervical carcinoma
      in human immunodeficiency virus-infected women.
AB  - BACKGROUND: Women infected with human immunodeficiency virus (HIV) are at
      increased risk of developing precancerous and cancerous lesions in cervix because
      of persistence of oncogenic human papillomavirus (HPV) infection. Scarce
      information about the HPV genotypes attributed to cervical cancer in the HIV
      infected population is available, especially in countries with a low prevalence
      of this pathology. OBJECTIVE: The objective of the study was to assess the
      prevalence and distribution of HPV types, and the viral integration of HPV-16 and
      HPV-18 in cervical squamous cell carcinoma of HIV-infected and HIV-negative
      women. METHODS: A total of 140 formaldehyde-fixed paraffin-embedded specimens
      from 31 HIV-infected and 109 matched HIV-negative women, with a diagnosis of in
      situ or invasive cervical carcinoma, were identified between 1987 and 2010 from
      different hospitals of the Barcelona area, Spain. Human papillomavirus genotyping
      and integration were analyzed by standardized polymerase chain reaction. RESULTS:
      Similar prevalence and distribution of HPV genotypes were detected in cervical
      cancers (in situ and invasive) regardless of HIV condition. The most common types
      were as follows: HPV-16 (58% in HIV-positive vs 72% in HIV-negative) and HPV-33
      (16% vs 8%). In invasive cervical carcinoma, HPV-18 was significantly more
      prevalent in HIV-positive women (14% vs 1%; P = 0.014). The proportion of samples
      with integrated forms of HPV-16 (39% vs 45%) and HPV-18 (50% vs 50%) was similar
      in both groups. CONCLUSIONS: The prevalence and distribution of principal HPV
      types involved in the carcinogenesis process of the cervix were similar in HIV
      infected and noninfected women, although a tendency toward a lower HPV-16 and a
      higher HPV-18 prevalence in invasive cervical carcinoma was detected in HIV
      positive women. Similar percentage of HPV-16 and HPV-18 viral integration was
      found in formaldehyde-fixed paraffin-embedded specimens of cervical cancer
      regardless of the HIV infection status.

PMID- 21892093
TI  - Trop-2 overexpression in poorly differentiated endometrial endometrioid
      carcinoma: implications for immunotherapy with hRS7, a humanized anti-trop-2
      monoclonal antibody.
AB  - OBJECTIVE: We evaluated the expression of human trophoblast cell surface marker
      (Trop-2) in endometrial endometrioid carcinoma (EEC) and the potential
      application of hRS7, a humanized monoclonal anti-Trop-2 antibody, as a
      therapeutic agent against poorly differentiated EEC. METHODS: Trop-2 expression
      was evaluated by immunohistochemistry in 131 EEC with different degrees of
      differentiation and 32 normal endometrial controls (NEC). Trop-2 expression was
      also evaluated by quantitative real-time polymerase chain reaction and flow
      cytometry in 3 primary EEC cell lines derived from patients harboring poorly
      differentiated EEC. Finally, the sensitivity of grade 3 EEC cell lines to hRS7
      antibody-dependent cellular cytotoxicity was tested in standard 5-hour Cr release
      assays. RESULTS: Trop-2 expression was detected in 126 (96.2%) of 131 EEC
      samples. Tumor tissues showed markedly increased Trop-2 positivity compared with
      NEC (P = 0.001). Trop-2 expression was significantly higher in all grades of EEC
      versus NEC. Grade 3 tumors displayed significantly stronger Trop-2 immunostaining
      compared with grade 1 EEC (P = 0.01). High Trop-2 expression by quantitative real
      time polymerase chain reaction and flow cytometry was found in 1 grade 3 EEC
      primary cell line (EEC-ARK-1). Unlike Trop-2-negative EEC cell lines, EEC-ARK-1
      was found highly sensitive to hRS7-mediated antibody-dependent cellular
      cytotoxicity in vitro (range of killing, 33.9%-50.6%; P = 0.004). Human serum did
      not significantly inhibit hRS7-mediated cytotoxicity against EEC-ARK-1 (P =
      0.773). CONCLUSIONS: Trop-2 is highly expressed in EEC, and its expression is
      significantly higher in poorly differentiated EEC when compared with well
      differentiated EEC. Primary grade 3 EECs overexpressing Trop-2 are highly
      sensitive to hRS7-mediated cytotoxicity in vitro. hRS7 may represent a novel
      therapeutic agent for the treatment of high-grade EEC refractory to standard
      treatment modalities.

PMID- 21892094
TI  - Risk factors for high-risk human papillomavirus infection and cofactors for high
      grade cervical disease in Peru.
AB  - OBJECTIVE: To evaluate the association between potential risk factors for high
      risk human papillomavirus (HR-HPV) infection and cofactors for cervical
      intraepithelial lesions grade 2 or worse (CIN2+) in women attending cervical
      screening in Amazonian Peru. MATERIALS AND METHODS: Participants completed a risk
      factor questionnaire before screening. High-risk human papillomavirus infection
      was determined by Hybrid Capture II. Logistic regression was used to evaluate
      associations between potential risk factors for HR-HPV infection and between
      cofactors and risk of CIN2+ among women with HR-HPV infection. RESULTS: Screening
      and questionnaires were completed by 5435 women aged 25 to 49 years. The
      prevalence of HR-HPV was 12.6% (95% confidence interval [CI], 11.8%-13.6%) and
      decreased by age. Early age at first sexual intercourse and several lifetime
      sexual partners increased the risk of having HR-HPV (age-adjusted odds ratio
      [AOR] of age at first sexual intercourse <18 vs >=20, 1.5; 95% CI, 1.2-2.0; AOR
      of >=5 lifetime sexual partners vs 1, 2.1; 95% CI, 1.4-3.2). Among women with HR
      HPV infection, those with no schooling (AOR relative to 1-5 years of schooling,
      3.2; 95% CI, 1.3-8.3) and those with parity >=3 (AOR relative to parity <3, 2.6;
      95% CI, 1.4-4.9) were at increased risk of CIN2+. The effect of parity was
      stronger for cancer (AOR of parity >=3 vs <3, 8.3; 95% CI, 1.0-65.6). Further
      analysis showed that the association between parity and CIN2+ was restricted to
      women younger than 40. Most women (83%) had previously been screened. Sixty-four
      percent of CIN2+ cases detected in this study occurred in women who reported
      having had a Papanicolaou test in the previous 3 years. Only 4 of 20 cancers were
      detected in women never screened before. Having had a previous abnormal
      Papanicolaou test increased the risk of CIN2+ (OR, 16.1; 95% CI, 6.2-41.9).
      CONCLUSION: Among women with HR-HPV, high parity (in young women), no schooling,
      lack of good-quality screening and of adequate follow-up care are the main risk
      factors for high-grade cervical disease in Peru.

PMID- 21892095
TI  - Routine hysterectomy in the surgical management of ovarian cancer: a
      retrospective case series, physician opinion survey, and review of the
      literature.
AB  - Current international guidelines recommend routine hysterectomy in the initial
      surgical management of epithelial ovarian cancer. However, there seems to be
      limited evidence to support these recommendations. We examined the data for a
      series of women undergoing hysterectomy as part of surgical management of ovarian
      cancer. Most of the women who underwent hysterectomy had no macroscopic uterine
      involvement in the ovarian cancer. However, almost half of them had macroscopic
      residual disease at completion of cytoreductive surgery. The incidence of
      synchronous primary endometrial cancers was 5%, and preoperative ultrasound had a
      sensitivity of 82% for predicting endometrial pathology. We also surveyed the
      members of the Australian Society of Gynaecological Oncologists (ASGO) regarding
      the role of hysterectomy in the management of ovarian cancer. Most of the
      respondents indicated that they believe hysterectomy should be routinely
      performed in the management of ovarian cancer but acknowledge that there is a
      lack of evidence to support the practice.

PMID- 21892096
TI  - Current clinical practice in cytoreductive surgery for advanced ovarian cancer: a
      European survey.
AB  - BACKGROUND: Surgical treatment of advanced ovarian cancer is a subject of fast
      development. The aim of this survey was to collect data on current surgical
      treatment from selected European gynecological oncology centers. METHODS: A
      questionnaire has been sent to gynecological oncology centers from 18 countries
      across Europe, which are presented on the ESGO Web site. Data were collected on
      an anonymous basis. All questions were related to the cytoreductive surgery of
      advanced ovarian cancer. RESULTS: Response rate reached 63%, and data from 17
      European countries were analyzed. The median number of new patients with ovarian
      cancer treated annually in a single centre was 95. Whereas 19% of centers perform
      infracolic omentectomy only, 81% carry on total omentectomy. Approximately half
      of the centers conduct appendectomy in all patients with advanced ovarian cancer,
      1/3 only if the appendix is macroscopically involved. Lymphadenectomy is carried
      out in 20% of centers in all cases but in 31% only if no residual disease is
      achieved. Proportion of patients in whom colorectal resection is performed ranged
      from less than 5% to more than 40%. Colorectal resection, splenectomy and liver
      resection are conducted by gynecological oncologist in 27%, 46%, and 12%,
      respectively. CONCLUSIONS: There were substantial differences in the spectrum and
      complexity of procedures performed in patients with advanced ovarian cancer among
      large European gynecologic oncology centers. Tendency to more complex surgery was
      shown in centers with a higher number of cases. Selected bowel and upper
      abdominal procedures are already performed by gynecological oncologists in large
      proportion of centers, without existence of well-established postgraduate
      training program.

PMID- 21892097
TI  - Is a low dose of concomitant chemotherapy with extended-field radiotherapy
      acceptable as an efficient treatment for cervical cancer patients with metastases
      to the para-aortic lymph nodes?
AB  - INTRODUCTION: Extended-field radiotherapy (EFRT) with the concomitant
      administration of chemotherapy for patients with advanced cervical cancer has
      problems regarding its feasibility. The goal of the present study was to assess
      the tolerability and control rate of low-dose cisplatin with EFRT in patients
      with imaging-confirmed positive para-aortic lymph nodes (PALs). METHODS: Sixteen
      patients with cervical cancer metastatic to the PALs treated with EFRT were
      evaluated. The patients included those with stages I to III disease according to
      the International Federation of Gynecology and Obstetrics with positive PALs
      diagnosed by computed tomographic imaging. The patients were treated with 25 to
      30 mg/m weekly of cisplatin concurrently with radiation therapy. Doses of 48.6 to
      51.0 Gy were delivered in 1.8-Gy fractions to the pelvis and included the PALs
      field. In addition, boost doses for the involved nodes of PALs were delivered
      contiguously for a total dose of 54 to 60 Gy. All patients were treated with a
      high dose rate of intracavitary brachytherapy combined with external irradiation.
      RESULTS: All patients completed the radiation therapy. Grade 3 or 4 acute
      hematologic toxicity occurred in 7 patients, but there were no cases of grade 3
      or 4 nonhematologic acute toxicity. As a late toxicity, 1 patient developed a
      grade 3 small bowel obstruction. No grade 4 or worse late toxicity occurred. The
      4-year overall survival rate was 56.3%. The 4-year distant metastasis-free
      survival rate was 50%. Seven patients had no recurrence. Eight patients developed
      distant failures, and another had an isolated local intrapelvic recurrence.
      CONCLUSIONS: A dose greater than 54 Gy for positive PALs in EFRT, in combination
      with intracavitary irradiation and low-dose weekly cisplatin administration, was
      safely completed by all of our patients. However, half of the patients had
      distant failure. This study provided relatively favorable local control and
      survival. Further considering modifications of the treatment should therefore be
      encouraged.

PMID- 21892098
TI  - Previous conization on patient eligibility of sentinel lymph node detection for
      early invasive cervical cancer.
AB  - OBJECTIVE: Sentinel lymph node (SLN) detection has been accepted as a common
      strategy to preserve the quality of life of the patients with gynecologic
      cancers. However, the feasibility of SLN detection after conization is not yet
      clarified. Accuracy of SLN after conization was evaluated. METHODS: Eighteen
      cases with prior conization (cone group) and 32 cases without conization (noncone
      group), all of which belonged to IB1 except 1 case in IA stage, underwent SLN
      detection. Systemic pelvic and para-aortic lymphadenectomy was coincidently
      performed for the estimation of negative and positive predictive values. RESULTS:
      Detection rate in which at least unilateral nodes were identified or bilaterally
      identified was 100% and 72.2% in the cone group, 90.6% and 71.9% in the noncone
      group, respectively. The average number of the detected SLN was 2.4 in the cone
      group and 2.1 in the noncone group. Negative and positive predictive value was
      100% in both groups. On the distribution of sentinel node stations, most of the
      detected nodes were internal iliac and obturator node in both groups. Less
      frequent detection was observed in superficial common iliac node (5.4% in the
      cone group, 3.1% in the noncone group), external iliac node (2.7% and 9.5%), and
      parauterine artery node (5.4% and 1.6%).In both groups, no other lymph nodes were
      identified as SLN except 1 case in the cone group with the node in cardinal
      ligament. CONCLUSIONS: No significant difference was observed on detection rate,
      predictive value, and the distribution of sentinel node between the cone and
      noncone groups. Sentinel lymph node detection after conization can be performed
      with a certain reliability.

PMID- 21892099
TI  - Association of the expression of mutant epidermal growth factor receptor protein
      as determined with mutation-specific antibodies in non-small cell lung cancer
      with progression-free survival after gefitinib treatment.
AB  - INTRODUCTION: Somatic mutations in the epidermal growth factor receptor (EGFR)
      gene are associated with an increased response to EGFR tyrosine kinase inhibitors
      (TKIs) such as gefitinib in patients with non-small cell lung cancer (NSCLC).
      Although most NSCLC patients with EGFR mutations benefit from EGFR-TKI treatment,
      the efficacy of such treatment varies among individuals. Molecular markers for
      prediction of EGFR-TKI treatment efficacy in EGFR mutation-positive NSCLC have
      not been well defined. METHODS: The expression of mutant EGFR proteins was
      quantitated by immunohistochemical analysis with mutation-specific antibodies in
      tumor specimens from 47 NSCLC patients with postoperative recurrent disease who
      harbored activating EGFR mutations. The expression score was determined from both
      the staining intensity and the proportion of tumor tissue expressing the mutant
      EGFR. RESULTS: The median progression-free survival after the start of gefitinib
      treatment was significantly longer in patients with a high score for mutant EGFR
      expression than in those with a low score (12.2 versus 3.4 months, p < 0.001),
      whereas no significant difference in median overall survival was apparent between
      the two groups (24.9 versus 17.7 months, respectively, p = 0.144). This
      association between the expression score for mutant EGFR and progression-free
      survival was apparent both in patients with deletions in exon 19 of EGFR and in
      those with the L858R mutation in exon 21. CONCLUSIONS: Quantitative analysis of
      mutant EGFR expression by immunohistochemical analysis with mutation-specific
      antibodies may predict the efficacy of gefitinib treatment for EGFR mutation
      positive NSCLC.

PMID- 21892100
TI  - Skin toxicities compromise prolonged pemetrexed treatment.
AB  - INTRODUCTION: Pemetrexed is approved to treat non-small cell lung cancer and has
      an overall favorable toxicity profile. A case of pemetrexed-induced cutaneous
      adverse events (CAE), i.e., periorbital edema with conjunctivitis and edema of
      the limbs, leading to severe fluid retention, was diagnosed in our unit. The aim
      of this study was to evaluate the incidence and risk factors for CAEs. METHODS:
      Patients treated with pemetrexed were identified from a prospective cohort. To
      detect pemetrexed-associated CAEs, questionnaires were answered by patients and
      the referring oncologist. RESULTS: Included were 107 patients treated with four
      cycles or more of pemetrexed. Pemetrexed-induced CAEs were observed in 37 of 107
      (35%) total patients (TPs) and 25 of 47 (53%) alive patients (APs).
      Conjunctivitis was the most frequent CAE: 27 of 107 (25%) in TPs and 21 of 47
      (44%) in APs. Periorbital edema occurred in 16 of 107 (15%) TPs and 14 of 47
      (30%) APs. Limb edema was present in 14 of 107 (13%) TPs and 12 of 47 (25%) APs.
      Only two cases of CAE influenced pemetrexed treatment. No significant differences
      in age, body surface area, smoking status, and performance status were detected.
      Patients with CAE had more cycles of pemetrexed (7 versus 5.5; p = 0.028). In
      univariate and multivariate analyses, gender ratio was statistically different (p
      = 0.031): 48% (12/25) of women in the CAE group versus only 18% (4/18) in the
      control group. CONCLUSION: Pemetrexed induces frequent conjunctivitis, peripheral
      edema, and edema of the limbs. Female gender seems to be an independent risk for
      CAE. CAEs are frequently disabling and symptomatic treatment should be proposed.

PMID- 21892102
TI  - Outcomes of stereotactic ablative radiotherapy for centrally located early-stage
      lung cancer.
AB  - INTRODUCTION: The use of stereotactic ablative radiotherapy (SABR) in centrally
      located early-stage lung tumors has been associated with increased toxicity. We
      studied outcomes after delivery of risk-adapted SABR of central tumors. METHODS:
      SABR was delivered in eight fractions of 7.5 Gy to 63 such patients between 2003
      and 2009. Of these, 37 patients had a tumor at a central hilar location, whereas
      26 patients had tumors abutting the pericardium or mediastinal structures.
      Survival outcomes were compared with patients with peripheral tumors treated
      during the same time period using fewer fractions of SABR. RESULTS: Median follow
      up was 35 months. Late grade III toxicity was limited to chest wall pain (n = 2)
      and increased dyspnoea (n = 2). No grade IV/V toxicity was observed, but grade V
      toxicity could not be excluded with certainty in nine patients who died of
      cardiopulmonary causes. Distant metastases were the predominant cause of death;
      cardiovascular deaths were not associated with a paracardial tumor location. No
      significant differences in outcomes were observed between these 63 patients and
      445 other SABR patients treated for peripheral early-stage lung tumors. Three
      year local control rates were 92.6% and 90.2% (p = 0.9). Three-year overall
      survival rates were 64.3% and 51.1% with median survival rates of 47 and 36
      months, in favor of the group of patients with central tumors (p = 0.09).
      CONCLUSIONS: Use of risk-adapted SABR delivered in eight fractions of 7.5 Gy did
      not result in excess toxicity for centrally located early-stage lung tumors, and
      clinical outcomes were comparable with those seen for peripheral lesions.

PMID- 21892101
TI  - Phase II trials of imatinib mesylate and docetaxel in patients with metastatic
      non-small cell lung cancer and head and neck squamous cell carcinoma.
AB  - PURPOSE: Two phase II clinical trials in the aerodigestive tumors were undertaken
      to evaluate the efficacy of imatinib mesylate-docetaxel. We hypothesized that
      imatinib mesylate would inhibit platelet-derived growth factor receptor (PDGFR)
      on pericytes and increase docetaxel uptake into tumor cells for an additive
      antitumor effect. Baseline tumor specimens, serum, and perfusion computed
      tomography (CT) scans were obtained for supportive evaluation. MATERIALS AND
      METHODS: Eligible patients with metastatic non-small cell lung cancer (NSCLC)
      treated with 1 prior therapy and chemonaive patients with head and neck squamous
      cell carcinoma (HNSCC) were enrolled in separate trials, which administered both
      docetaxel (60 mg/m every 3 weeks) and oral imatinib mesylate (400 mg daily). Both
      trials used interim analyses for efficacy and safety. RESULTS: Twenty-two
      patients with NSCLC and seven patients with HNSCC were enrolled. Both trials were
      closed early due to lack of efficacy, significant toxicity, and a potential
      antagonistic effect. In the NSCLC study, the response rate was 4.5%, median
      progression-free survival (PFS) 7.9 weeks, and overall survival 35.6 weeks. The
      HNSCC trial yielded a response rate 0%, PFS 8.8 weeks, and overall survival 34.7
      weeks. Baseline NSCLC tumor immunohistochemical biomarker analyses indicated that
      lower expression of stromal PDGFRbeta correlated with a better PFS, whereas
      stromal PDGFRalpha and tumor cell PDGFRbeta were associated with a worse clinical
      outcome when treated with imatinib mesylate-docetaxel. CONCLUSION: We do not
      recommend further investigation of this regimen in the aerodigestive tumors.
      Future investigations in PDGFR tyrosine kinase inhibitors should be used with
      caution in combination with taxanes and validation of the potential predictive or
      prognostic biomarkers stromal PDGFRalpha/beta, and tumor cell PDGFRbeta are
      needed.

PMID- 21892103
TI  - Combination chemotherapy with doxorubicin, vincristine, cyclophosphamide, and
      platinum compounds for advanced thymic carcinoma.
AB  - INTRODUCTION: Thymic carcinoma is a rare epithelial neoplasm that tends to be
      aggressive and metastasize widely. The optimal chemotherapy for unresectable
      advanced thymic carcinoma has not yet been established because of its rare
      occurrence. The purpose of this study was to evaluate the efficacy and
      tolerability of combination chemotherapy with doxorubicin, vincristine,
      cyclophosphamide, and platinum compounds for advanced thymic carcinoma. METHODS:
      A retrospective analysis of 34 patients with untreated and unresectable thymic
      carcinoma who received chemotherapy with doxorubicin, vincristine,
      cyclophosphamide, and platinum compounds between 1996 and 2010 was conducted.
      Twenty-nine patients were treated with a combination of cisplatin (50 mg/m(2))
      and doxorubicin (40 mg/m(2)) on day 1, vincristine (0.6 mg/m(2)) on day 3, and
      cyclophosphamide (700 mg/m(2)) on day 4. Five patients were treated with
      carboplatin (area under the curve of 3.0 minutes . mg/ml) instead of cisplatin.
      RESULTS: The responses of all 34 patients to the current regimen were assessed.
      The median number of treatment cycles for the present chemotherapy was 4. The
      overall response rate and disease control rate were 50.0% and 88.2%,
      respectively. The median survival was 21.3 months (95% confidence interval [CI],
      15.0-37.2 months), and the 1-year and 3-year survival rates were 72.7% (95% CI,
      56.8-88.6%) and 34.4% (95% CI, 16.2-52.6%), respectively. The most common adverse
      event was leukopenia/neutropenia, and nonhematological toxicities were mild.
      CONCLUSIONS: Combination chemotherapy with doxorubicin, vincristine,
      cyclophosphamide, and platinum compounds is an effective and well-tolerated
      treatment for unresectable advanced thymic carcinoma.

PMID- 21892104
TI  - Functional and clinical characterization of the putative tumor suppressor WWOX in
      non-small cell lung cancer.
AB  - INTRODUCTION: The oxidoreductase WWOX was initially described as a putative tumor
      suppressor in breast cancer. Non-small cell lung cancers (NSCLCs) frequently show
      aberrant WWOX expression. Herein, we characterized WWOX at a functional level in
      preclinical NSCLC models and in primary NSCLC biopsies. METHODS: The human wild
      type (wt) WWOX complementary DNA and a mutant WWOX with structurally disrupted
      short-chain dehydrogenase/reductase domain were conditionally expressed at
      physiological levels in several human NSCLC models. Resulting transgenic cell
      populations were analyzed with respect to clonogenic survival and apoptosis
      sensitivity in vitro and tumor growth in immune-deficient mice. Tissue
      microarrays prepared from surgically resected primary human NSCLC tumors were
      studied to correlate intratumoral WWOX expression with patient outcomes. RESULTS:
      Conditional expression of wt WWOX, but not mutant WWOX, suppressed clonogenic
      survival of NSCLC cells in vitro and tumor growth in vivo. In addition, preserved
      intratumoral WWOX expression was associated with improved outcome in a cohort of
      85 patients with surgically resected NSCLC. Unexpectedly, wt WWOX failed to
      sensitize NSCLC cells to various apoptotic stimuli but robustly protected against
      apoptosis induced by inhibitors of growth factor signal transduction.
      CONCLUSIONS: WWOX acts as a tumor suppressor in human NSCLC models in a short
      chain dehydrogenase/reductase domain-dependent manner. This activity is
      independent of sensitization to apoptotic cell death. WWOX expression as detected
      by immunohistochemistry may be a prognostic biomarker in surgically resected,
      early-stage NSCLC.

PMID- 21892105
TI  - Cost-effectiveness of computed tomography screening for lung cancer in the United
      States.
AB  - INTRODUCTION: A randomized trial has demonstrated that lung cancer screening
      reduces mortality. Identifying participant and program characteristics that
      influence the cost-effectiveness of screening will help translate trial results
      into benefits at the population level. METHODS: Six U.S. cohorts (men and women
      aged 50, 60, or 70 years) were simulated in an existing patient-level lung cancer
      model. Smoking histories reflected observed U.S. patterns. We simulated lifetime
      histories of 500,000 identical individuals per cohort in each scenario. Costs per
      quality-adjusted life-year gained ($/QALY) were estimated for each program:
      computed tomography screening; stand-alone smoking cessation therapies (4-30% 1
      year abstinence); and combined programs. RESULTS: Annual screening of current and
      former smokers aged 50 to 74 years costs between $126,000 and $169,000/QALY
      (minimum 20 pack-years of smoking) or $110,000 and $166,000/QALY (40 pack-year
      minimum), when compared with no screening and assuming background quit rates.
      Screening was beneficial but had a higher cost per QALY when the model included
      radiation-induced lung cancers. If screen participation doubled background quit
      rates, the cost of annual screening (at age 50 years, 20 pack-year minimum) was
      below $75,000/QALY. If screen participation halved background quit rates,
      benefits from screening were nearly erased. If screening had no effect on quit
      rates, annual screening costs more but provided fewer QALYs than annual cessation
      therapies. Annual combined screening/cessation therapy programs at age 50 years
      costs $130,500 to $159,700/QALY, when compared with annual stand-alone cessation.
      CONCLUSIONS: The cost-effectiveness of computed tomography screening will likely
      be strongly linked to achievable smoking cessation rates. Trials and further
      modeling should explore the consequences of relationships between smoking
      behaviors and screen participation.

PMID- 21892106
TI  - A randomized phase II trial of two regimens of moderate dose chemoradiation
      therapy for patients with non-small cell lung cancer not suitable for curative
      therapy: Trans Tasman Radiation Oncology Study TROG 03.07.
AB  - BACKGROUND: There are patients with stage I-III non-small cell lung cancer
      (NSCLC) who are not suitable for curative radical chemoradiation therapy. There
      are patients with an isolated solitary extracranial metastasis who have improved
      outcomes compared with those with cranial or multiple metastases. Patients of
      good performance status receiving moderate dose radiation therapy have improved
      survival. Two regimens of moderate dose chemoradiation therapy for such patients
      were compared in a randomized phase II trial. METHODS: Patients were eligible if
      they had stage I-IIIB NSCLC, unsuitable for curative therapy, or stage IV with a
      PET-detected extracranial solitary metastasis. Patients were randomized to the
      following groups-arm A: 40 Gy/20 fractions/4 weeks with concurrent weekly
      vinorelbine 25 mg/m + cisplatin 20 mg/m or arm B: 30 Gy/15 fractions/3 weeks with
      concurrent weekly gemcitabine 200 mg. Primary end points were feasibility,
      response rates, and toxicity. Secondary end points were progression-free
      survival, overall survival, and quality of life. RESULTS: Eighty-four patients
      were randomized. Compliance was above 90% for both arms. The overall response
      rate was 51% in arm A and 38% in arm B (p = 0.147). Grade 3/4 toxicity in both
      arms was acceptable. There was no difference in median progression-free survival
      between the two arms (5.5 versus 5.0 months, p = 0.19). Patients in arm A had
      longer median survival but this did not reach statistical significance (13.1
      versus 8.3 months, p = 0.25). No difference in quality of life was observed.
      CONCLUSIONS: Arm A was chosen for a future phase II comparison with radiation
      therapy alone as it demonstrated a response rate greater than 50%, and data
      suggested that arm A had superior survival to arm B.

PMID- 21892107
TI  - Lung cancer incidence and survival in England: an analysis by socioeconomic
      deprivation and urbanization.
AB  - INTRODUCTION: Most previous studies have investigated either socioeconomic
      deprivation or urbanization in relationship to lung cancer incidence or survival.
      We investigated the association between socioeconomic deprivation, urbanization,
      and lung cancer incidence and survival in England. METHODS: We extracted data on
      patients diagnosed with lung cancer (ICD-10 C33-C34) between 2003 and 2007 and
      who were resident in England. We assigned each patient to an urbanization score
      and to a socioeconomic quintile based on their postcode of residence. We
      calculated age-specific and age-standardized incidence rates (per 100,000
      European standard population) by urbanization, sex, and socioeconomic deprivation
      group. We used Kaplan-Meier survival analysis to compare the survival of patients
      from urban and rural areas by socioeconomic deprivation. RESULTS: A high
      proportion of urban areas in England were classified as deprived and rural areas
      were mostly affluent. The incidence of lung cancer was higher in urban areas than
      in rural areas. In the more affluent areas, the incidence of lung cancer in urban
      and rural areas was very similar. Survival from lung cancer was slightly higher
      in affluent areas than in deprived areas. Survival from lung cancer in urban and
      rural areas was similar across all socioeconomic deprivation quintiles.
      CONCLUSIONS: The difference in incidence between urban and rural areas can be
      explained by the differences in the distribution of socioeconomic deprivation
      quintiles in the two urbanization categories. When socioeconomic deprivation is
      taken into account, little difference is seen between both the incidence and
      survival of lung cancer in urban and rural areas.

PMID- 21892108
TI  - Survival benefits from follow-up of patients with lung cancer: a systematic
      review and meta-analysis.
AB  - INTRODUCTION: The burden of lung cancer is high for patients and carers. Care
      after treatment may have the potential to impact on this. We reviewed the
      published literature on follow-up strategies intended to improve survival and
      quality of life. METHODS: We systematically reviewed studies comparing follow-up
      regimes in lung cancer. Primary outcomes were overall survival (comparing more
      intensive versus less intensive follow-up) and survival comparing symptomatic
      with asymptomatic recurrence. Quality of life was identified as a secondary
      outcome measure. Hazard ratios (HRs) and 95% confidence intervals from eligible
      studies were synthesized. RESULTS: Nine studies that examined the role of more
      intensive follow-up for patients with lung cancer were included (eight
      observational studies and one randomized controlled trial). The studies of
      curative resection included patients with non-small cell lung cancer Stages I to
      III disease, and studies of palliative treatment follow-up included limited and
      extensive stage patients with small cell lung cancer. A total of 1669 patients
      were included in the studies. Follow-up programs were heterogeneous and
      multifaceted. A nonsignificant trend for intensive follow-up to improve survival
      was identified, for the curative intent treatment subgroup (HR: 0.83; 95%
      confidence interval: 0.66-1.05). Asymptomatic recurrence was associated with
      increased survival, which was statistically significant HR: 0.61 (0.50-0.74) (p <
      0.01); quality of life was only assessed in one study. CONCLUSIONS: This meta
      analysis must be interpreted with caution due to the potential for bias in the
      included studies: observed benefit may be due to systematic differences in
      outcomes rather than intervention effects. Some benefit was noted from intensive
      follow-up strategies. More robust data, in the form of randomized controlled
      trials, are needed to confirm these findings as the review is based primarily on
      observational studies. Future research should also include patient-centered
      outcomes to investigate the impact of follow-up regimes on living with lung
      cancer and psychosocial well-being.

PMID- 21892109
TI  - Intercalated erlotinib-docetaxel dosing schedules designed to achieve
      pharmacodynamic separation: results of a phase I/II trial.
AB  - INTRODUCTION: Epidermal growth factor receptor tyrosine kinase inhibitors given
      concurrently with chemotherapy do not improve patient outcomes compared with
      chemotherapy alone in advanced non-small cell lung cancer (NSCLC). On the basis
      of preclinical models, we hypothesized pharmacodynamic separation, achieved by
      intermittent delivery of epidermal growth factor receptor tyrosine kinase
      inhibitors intercalated with chemotherapy, as a reasonable strategy to deliver
      combination therapy. METHODS: A phase I dose-escalating trial using two
      scheduling strategies (arms A and B) was conducted in patients with advanced
      solid tumors to determine the feasibility of intermittent erlotinib and
      docetaxel. Phase II efficacy evaluation was conducted in an expanded cohort of
      patients with previously treated advanced NSCLC using arm B scheduling. Docetaxel
      was given every 21 days (70-75 mg/m intravenously) in both arms. In arm A,
      erlotinib was administered on days 2, 9, and 16 (600-1000 mg); in arm B,
      erlotinib was delivered on days 2 through 16 (150-300 mg). Patients without
      progression or unacceptable toxicity after six cycles continued erlotinib alone.
      RESULTS: Eighty-one patients were enrolled in this study (17 arm A; 25 arm B; and
      39 at phase II dose). Phase I patients had advanced solid tumors and 22 with
      NSCLC (10 and 12 patients for arms A and B, respectively). Treatment was well
      tolerated for both arms, with dose-limiting toxicities including grade 3
      infection and febrile neutropenia in arm A (maximum tolerated dose [MTD] of
      erlotinib 600 mg/docetaxel 70 mg/m) and grade 4 rash, febrile neutropenia, grade
      3 mucositis, and grade 3 diarrhea in arm B (MTD of erlotinib 200 mg/docetaxel 70
      mg/m). The MTD for arm B was chosen for phase II evaluation given the feasibility
      of administration, number of responses (one complete response and three partial
      responses), and achievement of pharmacodynamic separation. The response rate for
      patients treated at the phase II dose was 28.2%, and the disease control rate was
      64.1%. Median progression-free and overall survival were 4.1 and 18.2 months,
      respectively. Common grade >=3 toxicities were neutropenia (36%) and diarrhea
      (18%). CONCLUSIONS: Pharmacodynamic separation using intercalated schedules of
      erlotinib delivered on an intermittent basis together with docetaxel chemotherapy
      is feasible and tolerable. Further studies using this approach together with
      interrogation of relevant molecular pathways are ongoing.

PMID- 21892110
TI  - Renal stones, timing hypothesis, and eu-estrogenemia.
AB  - OBJECTIVE: The aim of this study was to apply the theory of the timing hypothesis
      to the data presented on the incidence of renal stones in the Women's Health
      Initiative and the theory of eu-estrogenemia. METHODS: The study is a review of
      the literature on the theory of renal stone formation and postmenopausal women,
      including data from the Nurses' Health Study and the Women's Health Initiative.
      RESULTS: The analysis of the hazard ratios and CIs of renal stones in the Women's
      Health Initiative shows that specific subgroups are affected. The CIs of the
      hazard ratios did not overlap 1.0 in the 60- to 64-year-old age group and in
      women whose time since menopause at study entry was 6 to 10 years. The CIs of all
      other age groups and years from menopause overlapped 1.0. Hormone therapy use by
      women described as "current users" at time of entry into the study in the
      treatment had a hazard ratio of 0.99. CONCLUSIONS: The timing hypothesis of
      Clarkson (Menopause 14:373-384; 2007) seems to explain the hazard ratio and CI of
      renal stones in the Women's Health Initiative. A closer analysis of the subgroups
      of women who had a higher incidence of renal stones suggests that the timing
      hypothesis may explain the results from the Women's Health Initiative versus
      previous studies such as the Nurses' Health Study. The CIs of the hazard ratios
      of the subgroups that did not overlap 1.0 included women 6 to 10 years beyond
      menopause, those who were aged from 60 to 64 years, and "never users" of hormone
      therapy. The hazard ratio for renal stones among "current users" in the Women's
      Health Initiative was 0.99. This analysis suggests that the timing hypothesis may
      affect estrogen receptor-alpha-mediated processes in the kidney. Furthermore,
      Clarkson's work may support the vascular etiology of renal stones.

PMID- 21892112
TI  - Tear menisci after overnight contact lens wear.
AB  - PURPOSE: To determine the effect of overnight wear of contact lenses (CL) on tear
      meniscus, tear film stability, and subjective comfort. METHODS: Sixty
      asymptomatic subjects were divided into three groups. The control group was
      composed of 20 non-CL wearers. Twenty inexperienced and 20 experienced CL wearers
      were enrolled as group 1 and group 2. For each subject in groups 1 and 2, a
      hydrogel and a silicone hydrogel CL were randomly assigned to each eye. Optical
      coherence tomography was used to determine volumes of the upper and lower tear
      menisci. Tear film stability was determined by non-invasive tear break-up time
      (NITBUT) measured by tearscope. A previously used questionnaire assessed dry eye
      symptoms. Subjects were evaluated during an 11-h period, including immediately
      before and after sleeping. RESULTS: Compared with the presleep levels, tear
      meniscus volume in the control group increased immediately after awakening and
      recovered by 1 hour later (p < 0.05). In contrast, tear meniscus volume in lens
      wearers increased on eye opening and recovered by 10 min later (p < 0.05). Tear
      meniscus volumes in CL wearers were less than those in controls at eye opening.
      NITBUT and comfort scores decreased immediately after CL insertion (p = 0.00).
      After eye opening, NITBUT was larger than the presleep levels until 10 min later.
      The comfort score was lower than the presleep values until 5 min later.
      CONCLUSIONS: Dynamic changes in the tear menisci, NITBUT, and comfort level were
      evident in both inexperienced and experienced CL wearers during and after
      overnight wear. Decreased tear meniscus volumes and tear film stability may
      contribute to lower eye comfort for extended CL wearers. The tearing on eye
      opening may facilitate improvement of ocular comfort and tear refreshment for a
      reconditioning of the tear system and the CL.

PMID- 21892113
TI  - Wolfram Syndrome: a rare optic neuropathy in youth with type 1 diabetes.
AB  - Wolfram Syndrome (WS) is a rare, autosomal recessive disorder that causes non
      autoimmune type 1 diabetes. The etiology involves a single gene mutation of the
      wolframin protein inducing endoplasmic reticulum stress and apoptosis in selected
      cell types with resultant diabetes insipidus, diabetes mellitus, optic atrophy,
      and sensory-neural deafness. Symptoms are initially absent and signs within the
      posterior segment of the eye are usually the earliest indicator of WS.These cases
      characterize unusual and poorly described findings of pigmentary maculopathy in
      WS and illustrate the importance of collaboration between diabetes and eye care
      providers; especially in cases of non-autoimmune type 1 diabetes exhibiting
      atypical human leukocyte-associated antigen haplotypes.

PMID- 21892111
TI  - C-reactive protein is associated with aortic stiffness in a cohort of African
      American and white women transitioning through menopause.
AB  - OBJECTIVE: Arterial stiffness is a marker of cardiovascular health. Arterial
      stiffness and C-reactive protein (CRP) are linked to cardiovascular outcomes.
      Increases in both inflammation and arterial stiffness are known to occur with
      menopause. The association between CRP and arterial stiffness is well accepted;
      however, no study has determined whether there are differences in this
      association by menopause status and race, independent of age. METHODS: The cross
      sectional association between CRP and aortic pulse wave velocity (PWV), a
      validated measure of central arterial stiffening, was evaluated in 307 African
      American and white women enrolled in an ancillary study to the Study of Women's
      Health Across the Nation. Women were categorized into premenopausal or early
      perimenopausal (n = 185) and late perimenopausal or postmenopausal (n = 122).
      RESULTS: Natural log-transformed CRP was not associated with PWV in a linear
      regression model adjusted for age and cardiovascular risk factors (beta = 15.9, P
      = 0.11). Moreover, models stratified by menopause status showed a linear
      relationship between CRP and PWV among late perimenopausal or postmenopausal
      women (beta = 36.2, P = 0.049) but not for premenopausal or early perimenopausal
      women (beta = 5.9, P = 0.61). The menopause status * log-transformed CRP and
      menopause status * race interactions were significant in their respective models
      adjusted for age and risk factors (P = 0.03 for both); however, when combined
      into one model, the two interactions were slightly attenuated (P = 0.063 and
      0.052, respectively). CONCLUSIONS: Menopause is strengthening the association
      between CRP and PWV, independent of age, and this effect seems to be stronger
      among African American women. This study provides a potential mechanism for the
      increased risk of cardiovascular disease among postmenopausal women.

PMID- 21892114
TI  - Prescribing for hyperopia in childhood and teenage by academic optometrists.
AB  - PURPOSE: The purpose of this study was to examine the prescribing patterns of
      academic optometrists for infants, children, and teenagers with hyperopia and the
      factors that affected the decision to prescribe. A comparison was made to
      published guidelines for prescribing for hyperopia in children. METHODS: The
      Waterloo Eye Study (WatES) database is a database of all patients attending the
      Primary Care Clinic or the Pediatric Clinic at the School of Optometry,
      University of Waterloo, between February 2007 and January 2008. Records for 698
      patients aged from birth to 19 years with hyperopia but without strabismus or
      significant anisometropia were extracted. They were analyzed to determine the
      factors that predicted whether a child was prescribed spectacles and the 50%
      prescribing points for hyperopia and astigmatism according to age. RESULTS:
      Univariate analysis showed that the level of hyperopia, astigmatism, age,
      distance, and near phoria and presence of symptoms were associated with the
      prescription of spectacles (p < 0.05). Multivariate analysis showed that the
      prescription of spectacles was predicted by age, highest sphere (either right or
      left eye), highest cylinder, the presence of symptoms, and distance phoria. Among
      0 to 3 year olds, all the children with 5 D or more of hyperopia had been
      prescribed spectacles. Among the 4 to 6 year olds, this point was 3.25 D; and for
      the 7 to 19 year olds, it was 2.25 D. The levels at which 50% of the population
      had been prescribed spectacles was 3.7, 1.8, and 1.1 D for the 0 to 3 year olds,
      4 to 6 year olds, and 7 to 19 year olds, respectively. There was frequently a
      difference between the refraction and the prescription such that the younger
      children, in particular, were often under corrected for both hyperopia and
      astigmatism. CONCLUSIONS: The optometrists in this academic setting appear to
      follow the available optometric guidelines for prescribing for hyperopia. They
      tend to prescribe for lower levels of hyperopia than U.S. ophthalmologists.

PMID- 21892115
TI  - Eye for modeling visual distortion in central serous retinopathy.
AB  - PURPOSE: To present a simple mathematical eye model capable of modeling the
      metamorphopsia (visual distortion) reported by patients with central serous
      retinopathy (CSR). METHODS: A computer program was developed to perform the
      modeling. A simple wide-angle eye model was adapted to include a spherical edema
      added at the retina. The visual impression was taken as the projection of the
      retinal pattern back into object space, after the edema had been deflated to its
      undistorted state. The deflation of the edema was facilitated by assuming a
      simplified "spreading of photoreceptors" rule. Numerical examples have been
      included to demonstrate the use of the model. In particular, an Amsler grid was
      projected to the retina with CSR, to illustrate the associated geometrical
      distortion. RESULTS: The eye model predicted a pincushion-like distortion of an
      Amsler grid, that depended (for given height) on the radius of curvature of the
      CSR. A larger radius of curvature resulted in less pincushion distortion
      extending over a larger area. CONCLUSIONS: An eye model has been developed that
      simulates distortion because of CSR. The predicted visual impression of a
      spherical edema is a pincushion-like distortion. This model may have applications
      in benchmarking alternate chart designs for detecting CSR, investigating optical
      aberrations over the edema as well as simulating the visual effect of
      metamorphopsia in other retinal conditions.

PMID- 21892116
TI  - Non-invasive collection and examination of human corneal epithelial cells.
AB  - PURPOSE: To report the development of a new apparatus for non-invasive collection
      of human corneal epithelial cells. METHODS: Previous methods of non-invasive,
      irrigative corneal cell collection resulted in low cell yields limiting potential
      analysis. A new ocular surface cell collection apparatus (OSCCA) was designed to
      collect more epithelial cells from direct irrigation of the corneal surface to
      allow for clinical comparisons. Forty-five samples were obtained (unilateral or
      bilateral over seven visits) from five human participants. Cell yield, size,
      phenotype, and corneal staining (prior and post eye wash) were examined. RESULTS:
      On average 364 +/- 230 epithelial cells were collected from the cornea per eye.
      Epithelial cell sizes ranged from 8.21 to 51.69 MUm in diameter, and 67.30 to
      2098.85 MUm area. The proportion of corneal specific cells collected per sample
      was 75 +/- 14% as determined by positive K3 expression with AE5. On average, 77
      +/- 0.2% of epithelial cells harvested were nucleated, the remainder were non
      nucleated ghost cells. Corneal staining was reduced in the OSCCA-washed vs.
      contralateral non-washed eyes (p = 0.02). CONCLUSIONS: The OSCCA allows
      collection of human corneal epithelial cells with significantly higher yields,
      and greater specificity than previously reported. Reduced corneal staining
      observed post eye-wash demonstrated the safety of the technique, and its ability
      to remove cells directly from the corneal surface. The OSCCA could provide an
      objective non-invasive method of investigating pathological changes, effects of
      topical therapeutics, and impact of contact lenses and care-solutions of the
      cells of the ocular surface.

PMID- 21892117
TI  - Continuous facial nerve stimulating burr for otologic surgeries.
AB  - OBJECTIVE: To evaluate a continuous facial nerve (FN) stimulating burr (the
      StimBurGard) during otologic/neurotologic procedures in terms of safety and
      reliability when drilling in contact with the Fallopian canal (FC) of the mastoid
      segment of the FN. STUDY DESIGN: Prospective clinical trial. SETTING: Tertiary
      referral center. PATIENTS: Thirty-five patients operated through
      translabyrinthine (TL) approach for vestibular schwannoma removal were divided
      into 3 groups. Group 1 (5 patients): the stimulation current was set at 3 and
      then at 2 mA visualizing the localization of the burr when the first response at
      100-MUV threshold was obtained in the mastoid cavity. Group 2 (15 patients):
      exposure of the FC in the mastoid segment during TL approach was stopped when the
      first response was obtained at 1-mA stimulation; FC thickness in the second genu
      and mastoid segment of the FC was evaluated on a postoperative computed
      tomographic (CT) scan, and FC dehiscence observed on CT scan was compared with
      surgical observation. Group 3 (15 patients), exposure of the FC was performed as
      routinely done during a TL approach and surgical observation of FC dehiscence;
      stimulation values in mA at the 100 MUV threshold and FC thickness on
      postoperative CT scan were evaluated. In all cases, the stimulation value at the
      cerebellopontine angle root of the FN with a 100-MUV response threshold was
      measured before tumor resection. RESULTS: Group 1: stimulation at 3 mA occurred
      in aditus ad antrum and at 2 mA near the FC. Group 2: mean thickness of 1.09 +/-
      0.69 mm with 2 cases of radiologic dehiscence of the FN. Group 3: the stimulation
      threshold was 0.6 +/- 0.37 mA, and the thickness was 0.41 +/- 0.56 mm with 9
      cases of uncovered FN (p = 0.0082). In all patients, FN at brainstem was
      stimulated at 0.03 mA before VS dissection. CONCLUSION: Continuous FN stimulating
      burr by means of the StimBurGard system is a safe and effective tool for FN
      stimulation and identification. The integrity of FC is preserved in most cases
      when the stimulation intensity is 1 mA.

PMID- 21892118
TI  - Length of nerve gap defects correlates with incidence of nerve regeneration but
      not with recovery of taste function in patients with severed chorda tympani
      nerve.
AB  - OBJECTIVE: To evaluate the relationship between the length of nerve gap defects,
      incidence of nerve regeneration, and recovery of gustatory function after
      severing the chorda tympani nerve (CTN). STUDY DESIGN: Retrospective study.
      SETTING: University hospital. PATIENTS: Eighty-eight consecutive patients whose
      CTNs were severed during primary surgery and who underwent secondary surgery were
      included. Proximal and distal stumps of severed nerves were readapted or
      approximated during surgery. INTERVENTION: Therapeutic. MAIN OUTCOME MEASURES:
      Before and after surgery, the taste function was periodically evaluated using
      electrogustometry. Nerve gaps were classified into 4 groups: readaptation (Group
      1), 1 to 3 mm (Group 2), 4 to 6 mm (Group 3), and more than 7 mm (Group 4).
      RESULTS: Regenerated nerves in the tympanic segment were detected in 36 (41%) of
      the 88 patients during secondary surgery. The incidence of nerve regeneration was
      100% (10/10) in Group 1, 45% (10/22) in Group 2, 47% (9/19) in Group 3, and 19%
      (7/37) in Group 4. There was a significant difference between the length of nerve
      gap defects and incidence of nerve regeneration (p < 0.001). In the 36 patients
      with a regenerated CTN, the incidence of gustatory function recovery was 60%
      (6/10) in Group 1, 50% (5/10) in Group 2, 56% (5/9) in Group 3, and 43% (3/7) in
      Group 4. There was no significant difference between the length of nerve gap
      defects and incidence of taste function recovery. CONCLUSION: Reconstruction of a
      severed CTN is very important for regeneration. However, the regenerated CTN in
      the tympanic segment does not always reinnervate the fungiform papillae.

PMID- 21892119
TI  - The impact of platelet-derived growth factor on closure of chronic tympanic
      membrane perforations: a randomized, double-blind, placebo-controlled study.
AB  - OBJECTIVE: Patients with tympanic membrane (TM) perforations often have
      infections, and repetitive topical treatment may be required. These infections
      can be prevented by permanent closure of the TM perforation. Different surgical
      treatment options have been described, but noninvasive techniques may be
      preferred as they carry less risk than surgery. One noninvasive approach is to
      induce wound healing by application of growth factors. The effect and clinical
      use of applying topical platelet-derived growth factor (PDGF) for decrease of
      size and closure of chronic TM perforations is evaluated. STUDY DESIGN:
      Prospective, randomized, placebo-controlled, double-blind study. SETTING:
      Tertiary referral center. PATIENTS: Twenty patients with chronic suppurative
      otitis media without cholesteatoma for more than 3 months. INTERVENTION: Topical
      treatment with PDGF or placebo applied weekly to the TM for 6 weeks. MAIN OUTCOME
      MEASURES: Success rate, defined as a reduction of perforation size of 50% or more
      to determine relative changes of the perforation size; effect of initial size and
      location of TM perforation on success rate; and air and bone conduction
      thresholds to determine air-bone gap measured before treatment. RESULTS:
      Randomization made matching pretreatment perforation size of the 2 study groups
      impossible, and the initial rate perforation/TM was significantly smaller in the
      PDGF group. No difference between the 2 groups was found for perforation/TM less
      than 10%. However, success rate did not differ significantly between the 2 groups
      (power = 0.8), and the effect of PDGF was found to be small (-2%; standard
      deviation, +/-49%). Initial size and position of the TM perforation were not
      significant factors determining success. Mean air-bone gap for the frequencies of
      0.5, 1, 2, and 4 kHz was 22.5 dB. CONCLUSION: The topical application of PDGF as
      an office treatment for chronic otitis media is not a favorable alternative to
      surgery.

PMID- 21892120
TI  - Involvement of the anterior semicircular canal in posttraumatic benign paroxysmal
      positioning vertigo.
AB  - OBJECTIVE: To study the involvement of the different semicircular canals in
      posttraumatic benign paroxysmal positioning vertigo (BPPV) with special reference
      to the anterior canal (AC). STUDY DESIGN: Retrospective review. SETTING: Tertiary
      referral center. PATIENTS: Seventy-four BPPV patients. INTERVENTIONS:
      Neurotologic assessment with video-oculography; treatment of BPPV with the
      canalith repositioning procedure appropriate for the affected semicircular canal.
      MAIN OUTCOME MEASURES: Number of patients with AC, posterior canal (PC),
      horizontal canal (HC), and multiple-canal involvement in posttraumatic versus
      idiopathic BPPV. RESULTS: 85.1% of patients were classified as idiopathic BPPV,
      whereas 14.9% had a history of posttraumatic BPPV. The prevalence of AC BPPV was
      significantly higher in the posttraumatic group (27.3%) compared with that in the
      idiopathic group (3.2%; Fisher's exact test: p = 0.021). Multiple-canal
      (combined) BPPV was observed more frequently after head trauma (27.3%) compared
      with the idiopathic form of the disorder (1.6%; p = 0.009). In particular, the
      risk for combined AC/PC BPPV was greater in posttraumatic than idiopathic cases
      (odds ratio, 13.78; 95% confidence interval, 1.13-167.8). No significant
      differences were observed for the involvement of the PC and HC between the two
      groups. Two cases of combined AC/PC BPPV are presented with particular respect to
      the underlying trauma mechanism. CONCLUSION: Head trauma is a risk factor for AC
      and combined BPPV, in particular AC/PC BPPV. Involvement of the AC should
      especially be considered in patients who experienced head trauma resulting in a
      nonupright position of the body.

PMID- 21892121
TI  - The modified Romberg Balance Test: normative data in U.S. adults.
AB  - OBJECTIVE: To generate normative values for performance on the modified Romberg
      Test of Standing Balance on Firm and Compliant Support Surfaces stratified by
      age, sex, and race/ethnicity and to determine fall risk associated with different
      levels of performance. STUDY DESIGN: National cross-sectional survey. SETTING:
      Ambulatory examination centers. PATIENTS: U.S. adults 40 years and older who
      participated in the 2001-2004 National Health and Nutrition Examination Survey (n
      = 5,086). INTERVENTIONS: Time to failure on the modified Romberg Test of Standing
      Balance on Firm and Compliant Support Surfaces. MAIN OUTCOME MEASURES: History of
      falling in the previous 12 months. RESULTS: We observed that the time to failure
      decreased with increasing age across all sex and race/ethnicity categories. We
      found that once individuals went below a time to failure of 20 seconds, there was
      a significant greater than 3-fold increase in the odds of falling. In general,
      participants crossed the 20-second threshold at the age of 60 to 69 years.
      CONCLUSION: We established nationally representative normative values for
      performance on the modified Romberg test and noted differences in the rates of
      change across demographic groups. In addition, we demonstrated the fall risk
      associated with different levels of performance. These data will aid the
      clinician in interpreting and risk stratifying their patient's performance on
      this postural test.

PMID- 21892122
TI  - Melanocytic nevus of the external auditory canal.

PMID- 21892123
TI  - New bone formation in patients with cochlear implants and otosclerosis.

PMID- 21892124
TI  - Antibiotic treatment of Escherichia coli O157 infection and the risk of hemolytic
      uremic syndrome, Minnesota.
AB  - BACKGROUND: Infection with Escherichia coli O157 (O157) can lead to the
      development of hemolytic uremic syndrome (HUS). Treating O157 infections with
      antibiotics is a possible risk factor for HUS development; however, previous
      studies evaluating this relationship have yielded conflicting results. The
      objective of this study was to further evaluate this issue. METHODS: An age
      matched case-case comparison study comprising Minnesota residents less than 20
      years of age with culture-confirmed O157 infection who did (n = 66) or did not (n
      = 129) subsequently develop HUS was conducted. Subjects were identified through
      statewide surveillance activities by the Minnesota Department of Health from 1996
      to 2002. RESULTS: Overall antibiotic treatment was not associated with the
      development of HUS. Self-reported vomiting and female gender were significantly
      associated with the development of HUS. After adjustment for illness severity and
      gender, subjects who developed HUS were more likely to have been treated only
      with bactericidal antibiotics within the first 3 days (adjusted matched odds
      ratio [OR], 12.4; 95% confidence interval [CI], 1.4-110.3) or within the first 7
      days (OR, 18.0; 95% CI, 1.9-170.9) after the onset of diarrhea. In particular,
      the use of beta-lactams (penicillins or cephalosporins) in the first 3 days after
      diarrhea onset was also significant after adjustment (OR, 11.3; 95% CI, 1.2
      106.7). CONCLUSIONS: Individuals infected with O157 infection presenting with a
      more severe illness were at an increased risk of developing HUS. The use of
      bactericidal antibiotics, particularly beta-lactams, to treat O157 infection was
      associated with the subsequent development of HUS.

PMID- 21892126
TI  - Application of preparative high-speed counter-current chromatography for the
      separation of two alkaloids from the roots of Tabernaemontana catharinensis
      (Apocynaceae).
AB  - The methanolic extract of Tabernaemontana catharinensis (Apocynaceae) roots,
      which contains alkaloids with several biological activities, was separated on a
      preparative scale using high-speed counter-current chromatography. The optimum
      solvent system was found to be a mixture of CHCl(3)-MeOH-H(2)O [5:10:6 (v/v/v)]
      and led to a successful separation of two monoterpenic indole alkaloids,
      voachalotine (1) and 12-methoxy-N(b)-methylvoachalotine (2) in approximately 4.0
      hours. The alkaloids were all isolated at purities over 95%, and their structures
      were established on the basis of spectroscopic methods, including 1D and 2D NMR
      and EI/MS.

PMID- 21892125
TI  - t-Bu2SiF-derivatized D2-receptor ligands: the first SiFA-containing small
      molecule radiotracers for target-specific PET-imaging.
AB  - The synthesis, radiolabeling and in vitro evaluation of new silicon-fluoride
      acceptor (SiFA) derivatized D(2)-receptor ligands is reported. The SiFA
      technology simplifies the introduction of fluorine-18 into target specific
      biomolecules for Positron-Emission-Tomography (PET). However, one of the
      remaining challenges, especially for small molecules such as receptor-ligands, is
      the bulkiness of the SiFA-moiety. We therefore synthesized four Fallypride SiFA
      conjugates derivatized either directly at the benzoic acid ring system (SiFA
      DMFP, SiFA-FP, SiFA-DDMFP) or at the butyl-side chain (SiFA-M-FP) and tested
      their receptor affinities. We found D(2)-receptor affinities for all compounds in
      the nanomolar range (K(i(SiFA-DMFP)) = 13.6 nM, K(i(SiFA-FP)) = 33.0 nM, K(i(SiFA
      DDMFP)) = 62.7 nM and K(i(SiFA-M-FP)) = 4.21 nM). The radiofluorination showed
      highest yields when 10 nmol of the precursors were reacted with
      [(18)F]fluoride/TBAHCO(3) in acetonitrile. After a reversed phased cartridge
      purification the desired products could be isolated as an injectable solution
      after only 10 min synthesis time with radiochemical yields (RCY) of more than 40%
      in the case of SiFA-DMFP resulting in specific activities >41 GBq/umol (>1,100
      Ci/mmol). Furthermore, the radiolabeled products were shown to be stable in the
      injectable solutions, as well as in human plasma, for at least 90 min.

PMID- 21892127
TI  - Thermal and rheological properties of a family of botryosphaerans produced by
      Botryosphaeria rhodina MAMB-05.
AB  - Differential scanning calorimetry (DSC), thermogravimetry (TG) and Fourier
      transform infra-red spectroscopy (FT-IR) analyses were performed to investigate
      changes in the physico-chemical properties of botryosphaerans, a family of
      exopolysaccharides (EPS) produced by the fungus Botryosphaeria rhodina MAMB-05
      grown on glucose (EPS(GLC)), sucrose (EPS(SUC)) and fructose (EPS(FRU)). A slight
      endothermic transition and small mass loss attributable to the removal of water
      of hydration were observed in the DSC and TG analyses, respectively, for the
      three EPS samples. The FT-IR spectra confirmed no structural changes occurred
      during thermal treatment. Viscometry was utilized to obtain information on the
      rheological behaviour of the EPS in aqueous solutions. The Power Law and Cross
      Equations determined the natural pseudoplastic characteristics of the EPS.
      Comparatively, results obtained for EPS produced when B. rhodina MAMB-05 was
      grown on each of the three carbohydrate sources demonstrated similar apparent
      viscosity values for EPS(GLC) and EPS(SUC), while EPS(FRU) displayed the lowest
      apparent viscosity of the three botryosphaerans, suggesting a higher degree of
      ramification and lower Mw. EPS(GLC) and EPS(SUC) possessed similar degrees of
      ramification. The slight differences found in their viscosities can be explained
      by the differences in the type of branching among the three botryosphaerans, thus
      varying the strength of intermolecular interactions and consequently, consistency
      and viscosity. The physico-chemical studies of botryosphaerans represent the
      originality of this work, and the knowledge of these properties is an important
      criterion for potential applications.

PMID- 21892128
TI  - Bioactivity of Carica papaya (Caricaceae) against Spodoptera frugiperda
      (Lepidoptera: Noctuidae).
AB  - The composition of a chloroform seed extract of C. papaya was determined by GC
      MS. Nineteen compounds were identified, with oleic (45.97%), palmitic (24.1%) and
      stearic (8.52%) acids being the main components. The insecticidal and
      insectistatic activities of the extract and the three main constituents were
      tested. Larval duration increased by 3.4 d and 2.5 d when the extract was used at
      16,000 and 9,600 ppm, respectively, whereas the pupal period increased by 2.2 d
      and 1.1 d at the same concentrations. Larval viability values were 0%, 29.2%, and
      50% when the extract was applied at 24,000, 16,000, and 9,600 ppm, respectively;
      pupal viability was 42.9% and 66.7% at 16,000 and 9,600 ppm; and pupal weight
      decreased by 25.4% and 11.5% at 16,000 and 9,600 ppm. The larval viability of the
      main compounds was 33.3%, 48.5%, and 62.5% when exposed to 1,600 ppm of palmitic
      acid, oleic acid, or stearic acid, respectively.

PMID- 21892129
TI  - IBD: UV protection and dermatological screening needed for IBD patients exposed
      to thiopurines.

PMID- 21892130
TI  - Liver: Successful conversion of fibroblasts into liver cells.

PMID- 21892132
TI  - Colorectal cancer: Telomere length and risk of CRC.

PMID- 21892133
TI  - Gastrointestinal bleeding: PPIs shown to exacerbate NSAID injury in rats through
      dysbiosis.

PMID- 21892134
TI  - Barrett esophagus: Blood group linked to risk of cancer in patients with Barrett
      esophagus.

PMID- 21892135
TI  - Liver: Potential of resistance exercise as a lipid-lowering treatment for NAFLD
      that is independent of weight loss.

PMID- 21892136
TI  - Obesity: Orlistat 60 mg reduces levels of visceral adipose tissue in obese
      individuals.

PMID- 21892137
TI  - Orientation-specific signalling by thrombopoietin receptor dimers.
AB  - Ligand binding to the thrombopoietin receptor is thought to stabilize an active
      receptor dimer that regulates megakaryocyte differentiation and platelet
      formation, as well as haematopoietic stem cell renewal. By fusing a dimeric
      coiled coil in all seven possible orientations to the thrombopoietin receptor
      transmembrane (TM)-cytoplasmic domains, we show that specific biological effects
      and in vivo phenotypes are imparted by distinct dimeric orientations, which can
      be visualized by cysteine mutagenesis and crosslinking. Using functional assays
      and computational searches, we identify one orientation that represents the
      inactive dimeric state and another similar to a physiologically activated
      receptor. Several other dimeric orientations are identified that induce
      proliferation and in vivo myeloproliferative and myelodysplastic disorders,
      indicating the receptor can signal from several dimeric interfaces. The set of
      dimeric thrombopoietin receptors with different TM orientations may offer new
      insights into the activation of distinct signalling pathways by a single receptor
      and suggests that subtle differences in cytokine receptor dimerization provide a
      new layer of signalling regulation that is relevant for disease.

PMID- 21892139
TI  - What's wrong with correlative experiments?
AB  - Here, we make a case for multivariate measurements in cell biology with minimal
      perturbation. We discuss how correlative data can identify cause-effect
      relationships in cellular pathways with potentially greater accuracy than
      conventional perturbation studies.

PMID- 21892138
TI  - Crystal structures of an archaeal class II DNA photolyase and its complex with UV
      damaged duplex DNA.
AB  - Class II photolyases ubiquitously occur in plants, animals, prokaryotes and some
      viruses. Like the distantly related microbial class I photolyases, these enzymes
      repair UV-induced cyclobutane pyrimidine dimer (CPD) lesions within duplex DNA
      using blue/near-UV light. Methanosarcina mazei Mm0852 is a class II photolyase of
      the archaeal order of Methanosarcinales, and is closely related to plant and
      metazoan counterparts. Mm0852 catalyses light-driven DNA repair and
      photoreduction, but in contrast to class I enzymes lacks a high degree of binding
      discrimination between UV-damaged and intact duplex DNA. We solved crystal
      structures of Mm0852, the first one for a class II photolyase, alone and in
      complex with CPD lesion-containing duplex DNA. The lesion-binding mode differs
      from other photolyases by a larger DNA-binding site, and an unrepaired CPD lesion
      is found flipped into the active site and recognized by a cluster of five water
      molecules next to the bound 3'-thymine base. Different from other members of the
      photolyase-cryptochrome family, class II photolyases appear to utilize an
      unusual, conserved tryptophane dyad as electron transfer pathway to the catalytic
      FAD cofactor.

PMID- 21892140
TI  - Visualizing branched actin filaments in lamellipodia by electron tomography.

PMID- 21892143
TI  - Wnt: what's needed to maintain pluripotency?
AB  - A precise role for the canonical Wnt pathway in maintaining pluripotency in mouse
      embryonic stem cells (mESCs) has been debated. Four recent reports add pieces to
      the puzzle and together these results may help establish a robust model.

PMID- 21892142
TI  - The AMPK signalling pathway coordinates cell growth, autophagy and metabolism.
AB  - One of the central regulators of cellular and organismal metabolism in eukaryotes
      is AMP-activated protein kinase (AMPK), which is activated when intracellular ATP
      production decreases. AMPK has critical roles in regulating growth and
      reprogramming metabolism, and has recently been connected to cellular processes
      such as autophagy and cell polarity. Here we review a number of recent
      breakthroughs in the mechanistic understanding of AMPK function, focusing on a
      number of newly identified downstream effectors of AMPK.

PMID- 21892144
TI  - Coupling mitochondrial and cell division.
AB  - The mitochondrial network fragments during mitosis to allow proper segregation of
      the organelles between daughter cells. Two mitotic kinases, the cyclin B-CDK1
      complex and Aurora A, are now shown to cooperate with the small G protein RALA
      and its effector RALBP1 to promote DRP1 phosphorylation and mitochondrial
      fission.

PMID- 21892149
TI  - Believe it or not: how much can we rely on published data on potential drug
      targets?

PMID- 21892150
TI  - FaST linear mixed models for genome-wide association studies.
AB  - We describe factored spectrally transformed linear mixed models (FaST-LMM), an
      algorithm for genome-wide association studies (GWAS) that scales linearly with
      cohort size in both run time and memory use. On Wellcome Trust data for 15,000
      individuals, FaST-LMM ran an order of magnitude faster than current efficient
      algorithms. Our algorithm can analyze data for 120,000 individuals in just a few
      hours, whereas current algorithms fail on data for even 20,000 individuals
      (http://mscompbio.codeplex.com/).

PMID- 21892152
TI  - Firefly luciferase mutants as sensors of proteome stress.
AB  - Maintenance of cellular protein homeostasis (proteostasis) depends on a complex
      network of molecular chaperones, proteases and other regulatory factors.
      Proteostasis deficiency develops during normal aging and predisposes individuals
      for many diseases, including neurodegenerative disorders. Here we describe sensor
      proteins for the comparative measurement of proteostasis capacity in different
      cell types and model organisms. These sensors are increasingly structurally
      destabilized versions of firefly luciferase. Imbalances in proteostasis manifest
      as changes in sensor solubility and luminescence activity. We used EGFP-tagged
      constructs to monitor the aggregation state of the sensors and the ability of
      cells to solubilize or degrade the aggregated proteins. A set of three sensor
      proteins serves as a convenient toolkit to assess the proteostasis status in a
      wide range of experimental systems, including cell and organism models of stress,
      neurodegenerative disease and aging.

PMID- 21892151
TI  - Toward the blood-borne miRNome of human diseases.
AB  - In a multicenter study, we determined the expression profiles of 863 microRNAs by
      array analysis of 454 blood samples from human individuals with different cancers
      or noncancer diseases, and validated this 'miRNome' by quantitative real-time
      PCR. We detected consistently deregulated profiles for all tested diseases;
      pathway analysis confirmed disease association of the respective microRNAs. We
      observed significant correlations (P = 0.004) between the genomic location of
      disease-associated genetic variants and deregulated microRNAs.

PMID- 21892153
TI  - Induced pluripotent stem cells from highly endangered species.
AB  - For some highly endangered species there are too few reproductively capable
      animals to maintain adequate genetic diversity, and extraordinary measures are
      necessary to prevent extinction. We report generation of induced pluripotent stem
      cells (iPSCs) from two endangered species: a primate, the drill, Mandrillus
      leucophaeus and the nearly extinct northern white rhinoceros, Ceratotherium simum
      cottoni. iPSCs may eventually facilitate reintroduction of genetic material into
      breeding populations.

PMID- 21892154
TI  - Experience-dependent expression of miR-132 regulates ocular dominance plasticity.
AB  - miR-132 is a CREB-induced microRNA that is involved in dendritic spine
      plasticity. We found that visual experience regulated histone post-translational
      modifications at a CRE locus that is important for miR-212 and miR-132 cluster
      transcription, and regulated miR-132 expression in the visual cortex of juvenile
      mice. Monocular deprivation reduced miR-132 expression in the cortex
      contralateral to the deprived eye. Counteracting this miR-132 reduction with an
      infusion of chemically modified miR-132 mimic oligonucleotides completely blocked
      ocular dominance plasticity.

PMID- 21892155
TI  - miR-132, an experience-dependent microRNA, is essential for visual cortex
      plasticity.
AB  - Using quantitative analyses, we identified microRNAs (miRNAs) that were
      abundantly expressed in visual cortex and that responded to dark rearing and/or
      monocular deprivation. The most substantially altered miRNA, miR-132, was rapidly
      upregulated after eye opening and was delayed by dark rearing. In vivo inhibition
      of miR-132 in mice prevented ocular dominance plasticity in identified neurons
      following monocular deprivation and affected the maturation of dendritic spines,
      demonstrating its critical role in the plasticity of visual cortex circuits.

PMID- 21892156
TI  - Constructing scenes from objects in human occipitotemporal cortex.
AB  - We used functional magnetic resonance imaging (fMRI) to demonstrate the existence
      of a mechanism in the human lateral occipital (LO) cortex that supports
      recognition of real-world visual scenes through parallel analysis of within-scene
      objects. Neural activity was recorded while subjects viewed four categories of
      scenes and eight categories of 'signature' objects strongly associated with the
      scenes in three experiments. Multivoxel patterns evoked by scenes in the LO
      cortex were well predicted by the average of the patterns elicited by their
      signature objects. By contrast, there was no relationship between scene and
      object patterns in the parahippocampal place area (PPA), even though this region
      responds strongly to scenes and is believed to be crucial for scene
      identification. By combining information about multiple objects within a scene,
      the LO cortex may support an object-based channel for scene recognition that
      complements the processing of global scene properties in the PPA.

PMID- 21892157
TI  - Engrailed protects mouse midbrain dopaminergic neurons against mitochondrial
      complex I insults.
AB  - Mice heterozygous for the homeobox gene Engrailed-1 (En1) display progressive
      loss of mesencephalic dopaminergic (mDA) neurons. We report that exogenous
      Engrailed-1 and Engrailed-2 (collectively Engrailed) protect mDA neurons from 1
      methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a mitochondrial complex I
      toxin used to model Parkinson's disease in animals. Engrailed enhances the
      translation of nuclearly encoded mRNAs for two key complex I subunits, Ndufs1 and
      Ndufs3, and increases complex I activity. Accordingly, in vivo protection against
      MPTP by Engrailed is antagonized by Ndufs1 small interfering RNA. An association
      between Engrailed and complex I is further confirmed by the reduced expression of
      Ndufs1 and Ndufs3 in the substantia nigra pars compacta of En1 heterozygous mice.
      Engrailed also confers in vivo protection against 6-hydroxydopamine and alpha
      synuclein-A30P. Finally, the unilateral infusion of Engrailed into the midbrain
      increases striatal dopamine content, resulting in contralateral amphetamine
      induced turning. Therefore, Engrailed is both a survival factor for adult mDA
      neurons and a regulator of their physiological activity.

PMID- 21892158
TI  - Mutations in GATA2 cause primary lymphedema associated with a predisposition to
      acute myeloid leukemia (Emberger syndrome).
AB  - We report an allelic series of eight mutations in GATA2 underlying Emberger
      syndrome, an autosomal dominant primary lymphedema associated with a
      predisposition to acute myeloid leukemia. GATA2 is a transcription factor that
      plays an essential role in gene regulation during vascular development and
      hematopoietic differentiation. Our findings indicate that haploinsufficiency of
      GATA2 underlies primary lymphedema and predisposes to acute myeloid leukemia in
      this syndrome.

PMID- 21892159
TI  - Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic
      leukemia.
AB  - Interleukin 7 (IL-7) and its receptor, formed by IL-7Ralpha (encoded by IL7R) and
      gammac, are essential for normal T-cell development and homeostasis. Here we show
      that IL7R is an oncogene mutated in T-cell acute lymphoblastic leukemia (T-ALL).
      We find that 9% of individuals with T-ALL have somatic gain-of-function IL7R exon
      6 mutations. In most cases, these IL7R mutations introduce an unpaired cysteine
      in the extracellular juxtamembrane-transmembrane region and promote de novo
      formation of intermolecular disulfide bonds between mutant IL-7Ralpha subunits,
      thereby driving constitutive signaling via JAK1 and independently of IL-7, gammac
      or JAK3. IL7R mutations induce a gene expression profile partially resembling
      that provoked by IL-7 and are enriched in the T-ALL subgroup comprising TLX3
      rearranged and HOXA deregulated cases. Notably, IL7R mutations promote cell
      transformation and tumor formation. Overall, our findings indicate that IL7R
      mutational activation is involved in human T-cell leukemogenesis, paving the way
      for therapeutic targeting of IL-7R-mediated signaling in T-ALL.

PMID- 21892160
TI  - Germline deletion of the miR-17~92 cluster causes skeletal and growth defects in
      humans.
AB  - MicroRNAs (miRNAs) are key regulators of gene expression in animals and plants.
      Studies in a variety of model organisms show that miRNAs modulate developmental
      processes. To our knowledge, the only hereditary condition known to be caused by
      a miRNA is a form of adult-onset non-syndromic deafness, and no miRNA mutation
      has yet been found to be responsible for any developmental defect in humans. Here
      we report the identification of germline hemizygous deletions of MIR17HG,
      encoding the miR-17~92 polycistronic miRNA cluster, in individuals with
      microcephaly, short stature and digital abnormalities. We demonstrate that
      haploinsufficiency of miR-17~92 is responsible for these developmental
      abnormalities by showing that mice harboring targeted deletion of the miR-17~92
      cluster phenocopy several key features of the affected humans. These findings
      identify a regulatory function for miR-17~92 in growth and skeletal development
      and represent the first example of an miRNA gene responsible for a syndromic
      developmental defect in humans.

PMID- 21892161
TI  - Genomic sequencing of colorectal adenocarcinomas identifies a recurrent VTI1A
      TCF7L2 fusion.
AB  - Prior studies have identified recurrent oncogenic mutations in colorectal
      adenocarcinoma and have surveyed exons of protein-coding genes for mutations in
      11 affected individuals. Here we report whole-genome sequencing from nine
      individuals with colorectal cancer, including primary colorectal tumors and
      matched adjacent non-tumor tissues, at an average of 30.7* and 31.9* coverage,
      respectively. We identify an average of 75 somatic rearrangements per tumor,
      including complex networks of translocations between pairs of chromosomes. Eleven
      rearrangements encode predicted in-frame fusion proteins, including a fusion of
      VTI1A and TCF7L2 found in 3 out of 97 colorectal cancers. Although TCF7L2 encodes
      TCF4, which cooperates with beta-catenin in colorectal carcinogenesis, the fusion
      lacks the TCF4 beta-catenin-binding domain. We found a colorectal carcinoma cell
      line harboring the fusion gene to be dependent on VTI1A-TCF7L2 for anchorage
      independent growth using RNA interference-mediated knockdown. This study shows
      previously unidentified levels of genomic rearrangements in colorectal carcinoma
      that can lead to essential gene fusions and other oncogenic events.

PMID- 21892162
TI  - Heritable GATA2 mutations associated with familial myelodysplastic syndrome and
      acute myeloid leukemia.
AB  - We report the discovery of GATA2 as a new myelodysplastic syndrome (MDS)-acute
      myeloid leukemia (AML) predisposition gene. We found the same, previously
      unidentified heterozygous c.1061C>T (p.Thr354Met) missense mutation in the GATA2
      transcription factor gene segregating with the multigenerational transmission of
      MDS-AML in three families and a GATA2 c.1063_1065delACA (p.Thr355del) mutation at
      an adjacent codon in a fourth MDS family. The resulting alterations reside within
      the second zinc finger of GATA2, which mediates DNA-binding and protein-protein
      interactions. We show differential effects of the mutations on the
      transactivation of target genes, cellular differentiation, apoptosis and global
      gene expression. Identification of such predisposing genes to familial forms of
      MDS and AML is critical for more effective diagnosis and prognosis, counseling,
      selection of related bone marrow transplant donors and development of therapies.

PMID- 21892163
TI  - Nanopore-based detection of circulating microRNAs in lung cancer patients.
AB  - MicroRNAs are short RNA molecules that regulate gene expression, and have been
      investigated as potential biomarkers because their expression levels are
      correlated with various diseases. However, detecting microRNAs in the bloodstream
      remains difficult because current methods are not sufficiently selective or
      sensitive. Here, we show that a nanopore sensor based on the alpha-haemolysin
      protein can selectively detect microRNAs at the single molecular level in plasma
      samples from lung cancer patients without the need for labels or amplification of
      the microRNA. The sensor, which uses a programmable oligonucleotide probe to
      generate a target-specific signature signal, can quantify subpicomolar levels of
      cancer-associated microRNAs and can distinguish single-nucleotide differences
      between microRNA family members. This approach is potentially useful for
      quantitative microRNA detection, the discovery of disease markers and non
      invasive early diagnosis of cancer.

PMID- 21892164
TI  - Graphene plasmonics for tunable terahertz metamaterials.
AB  - Plasmons describe collective oscillations of electrons. They have a fundamental
      role in the dynamic responses of electron systems and form the basis of research
      into optical metamaterials. Plasmons of two-dimensional massless electrons, as
      present in graphene, show unusual behaviour that enables new tunable plasmonic
      metamaterials and, potentially, optoelectronic applications in the terahertz
      frequency range. Here we explore plasmon excitations in engineered graphene micro
      ribbon arrays. We demonstrate that graphene plasmon resonances can be tuned over
      a broad terahertz frequency range by changing micro-ribbon width and in situ
      electrostatic doping. The ribbon width and carrier doping dependences of graphene
      plasmon frequency demonstrate power-law behaviour characteristic of two
      dimensional massless Dirac electrons. The plasmon resonances have remarkably
      large oscillator strengths, resulting in prominent room-temperature optical
      absorption peaks. In comparison, plasmon absorption in a conventional two
      dimensional electron gas was observed only at 4.2 K (refs 13, 14). The results
      represent a first look at light-plasmon coupling in graphene and point to
      potential graphene-based terahertz metamaterials.

PMID- 21892165
TI  - Experimental demonstration of a single-molecule electric motor.
AB  - For molecules to be used as components in molecular machines, methods that couple
      individual molecules to external energy sources and that selectively excite
      motion in a given direction are required. Significant progress has been made in
      the construction of molecular motors powered by light and by chemical reactions,
      but electrically driven motors have not yet been built, despite several
      theoretical proposals for such motors. Here we report that a butyl methyl
      sulphide molecule adsorbed on a copper surface can be operated as a single
      molecule electric motor. Electrons from a scanning tunnelling microscope are used
      to drive the directional motion of the molecule in a two-terminal setup.
      Moreover, the temperature and electron flux can be adjusted to allow each
      rotational event to be monitored at the molecular scale in real time. The
      direction and rate of the rotation are related to the chiralities of both the
      molecule and the tip of the microscope (which serves as the electrode),
      illustrating the importance of the symmetry of the metal contacts in atomic-scale
      electrical devices.

PMID- 21892166
TI  - Gold nanoparticles for high-throughput genotyping of long-range haplotypes.
AB  - Completion of the Human Genome Project and the HapMap Project has led to
      increasing demands for mapping complex traits in humans to understand the
      aetiology of diseases. Identifying variations in the DNA sequence, which affect
      how we develop disease and respond to pathogens and drugs, is important for this
      purpose, but it is difficult to identify these variations in large sample sets.
      Here we show that through a combination of capillary sequencing and polymerase
      chain reaction assisted by gold nanoparticles, it is possible to identify several
      DNA variations that are associated with age-related macular degeneration and
      psoriasis on significant regions of human genomic DNA. Our method is accurate and
      promising for large-scale and high-throughput genetic analysis of susceptibility
      towards disease and drug resistance.

PMID- 21892167
TI  - The Rad50 coiled-coil domain is indispensable for Mre11 complex functions.
AB  - The Mre11 complex (Mre11, Rad50 and Xrs2 in Saccharomyces cerevisiae) influences
      diverse functions in the DNA damage response. The complex comprises the globular
      DNA-binding domain and the Rad50 hook domain, which are linked by a long and
      extended Rad50 coiled-coil domain. In this study, we constructed rad50 alleles
      encoding truncations of the coiled-coil domain to determine which Mre11 complex
      functions required the full length of the coils. These mutations abolished
      telomere maintenance and meiotic double-strand break (DSB) formation, and
      severely impaired homologous recombination, indicating a requirement for long
      range action. Nonhomologous end joining, which is probably mediated by the
      globular domain of the Mre11 complex, was also severely impaired by alteration of
      the coiled-coil and hook domains, providing the first evidence of their influence
      on this process. These data show that functions of Mre11 complex are integrated
      by the coiled coils of Rad50.

PMID- 21892168
TI  - Spliceosome assembly is coupled to RNA polymerase II dynamics at the 3' end of
      human genes.
AB  - In the nucleus of higher eukaryotes, maturation of mRNA precursors involves an
      orderly sequence of transcription-coupled interdependent steps. Transcription is
      well known to influence splicing, but how splicing may affect transcription
      remains unclear. Here we show that a splicing mutation that prevents recruitment
      of spliceosomal snRNPs to nascent transcripts causes co-transcriptional retention
      of unprocessed RNAs that remain associated with polymerases stalled predominantly
      at the 3' end of the gene. In contrast, treatment with spliceostatin A, which
      allows early spliceosome formation but destabilizes subsequent assembly of the
      catalytic complex, abolishes 3' end pausing of polymerases and induces leakage of
      unspliced transcripts to the nucleoplasm. Taken together, the data suggest that
      recruitment of splicing factors and correct assembly of the spliceosome are
      coupled to transcription termination, and this might ensure a proofreading
      mechanism that slows down release of unprocessed transcripts from the
      transcription site.

PMID- 21892169
TI  - Apo and InsP3-bound crystal structures of the ligand-binding domain of an InsP3
      receptor.
AB  - We report the crystal structures of the ligand-binding domain (LBD) of a rat
      inositol 1,4,5-trisphosphate receptor (InsP(3)R) in its apo and InsP(3)-bound
      conformations. Comparison of these two conformations reveals that LBD's first
      beta-trefoil fold (beta-TF1) and armadillo repeat fold (ARF) move together as a
      unit relative to its second beta-trefoil fold (beta-TF2). Whereas apo LBD may
      spontaneously transition between gating conformations, InsP(3) binding shifts
      this equilibrium toward the active state.

PMID- 21892170
TI  - Structural analysis of the interaction between Hsp90 and the tumor suppressor
      protein p53.
AB  - In eukaryotes, the essential dimeric molecular chaperone Hsp90 is required for
      the activation and maturation of specific substrates such as steroid hormone
      receptors, tyrosine kinases and transcription factors. Hsp90 is involved in the
      establishment of cancer and has become an attractive target for drug design. Here
      we present a structural characterization of the complex between Hsp90 and the
      tumor suppressor p53, a key mediator of apoptosis whose structural integrity is
      crucial for cell-cycle control. Using biophysical methods, we show that the human
      p53 DNA-binding domain interacts with multiple domains of yeast Hsp90. p53 binds
      to the Hsp90 C-terminal domain in its native-like state in a charge-dependent
      manner, but it also associates weakly with binding sites in the middle and the N
      terminal domains. The fine-tuned interplay between several Hsp90 domains provides
      the interactions required for efficient chaperoning of p53.

PMID- 21892171
TI  - Defects in RNA quality control factors reveal RNAi-independent nucleation of
      heterochromatin.
AB  - Heterochromatin assembly at Schizosaccharomyces pombe centromeres involves a self
      reinforcing loop mechanism wherein chromatin-bound RNAi factors facilitate
      targeting of Clr4-Rik1 methyltransferase. However, the initial nucleation of
      heterochromatin has remained elusive. We show that cells lacking Mlo3, a protein
      involved in mRNP biogenesis and RNA quality control, assemble functional
      heterochromatin in RNAi-deficient cells. Heterochromatin restoration is linked to
      RNA surveillance because loss of Mlo3-associated TRAMP also rescues
      heterochromatin defects of RNAi mutants. mlo3Delta, which causes accumulation of
      bidirectional repeat-transcripts, restores Rik1 enrichment at repeats and
      triggers de novo heterochromatin formation in the absence of RNAi. RNAi
      independent heterochromatin nucleation occurs at selected euchromatic loci that
      show upregulation of antisense RNAs in mlo3Delta cells. We find that the exosome
      RNA degradation machinery acts parallel to RNAi to promote heterochromatin
      formation at centromeres. These results suggest that RNAi-independent mechanisms
      exploit transcription and non-coding RNAs to nucleate heterochromatin.

PMID- 21892172
TI  - The inflammasome adaptor ASC regulates the function of adaptive immune cells by
      controlling Dock2-mediated Rac activation and actin polymerization.
AB  - The adaptor ASC contributes to innate immunity through the assembly of
      inflammasome complexes that activate the cysteine protease caspase-1. Here we
      demonstrate that ASC has an inflammasome-independent, cell-intrinsic role in
      cells of the adaptive immune response. ASC-deficient mice showed defective
      antigen presentation by dendritic cells (DCs) and lymphocyte migration due to
      impaired actin polymerization mediated by the small GTPase Rac. Genome-wide
      analysis showed that ASC, but not the cytoplasmic receptor NLRP3 or caspase-1,
      controlled the mRNA stability and expression of Dock2, a guanine nucleotide
      exchange factor that mediates Rac-dependent signaling in cells of the immune
      response. Dock2-deficient DCs showed defective antigen uptake similar to that of
      ASC-deficient cells. Ectopic expression of Dock2 in ASC-deficient cells restored
      Rac-mediated actin polymerization, antigen uptake and chemotaxis. Thus, ASC
      shapes adaptive immunity independently of inflammasomes by modulating Dock2
      dependent Rac activation and actin polymerization in DCs and lymphocytes.

PMID- 21892173
TI  - Invariant natural killer T cells recognize glycolipids from pathogenic Gram
      positive bacteria.
AB  - Natural killer T cells (NKT cells) recognize glycolipid antigens presented by
      CD1d. These cells express an evolutionarily conserved, invariant T cell antigen
      receptor (TCR), but the forces that drive TCR conservation have remained
      uncertain. Here we show that NKT cells recognized diacylglycerol-containing
      glycolipids from Streptococcus pneumoniae, the leading cause of community
      acquired pneumonia, and group B Streptococcus, which causes neonatal sepsis and
      meningitis. Furthermore, CD1d-dependent responses by NKT cells were required for
      activation and host protection. The glycolipid response was dependent on vaccenic
      acid, which is present in low concentrations in mammalian cells. Our results show
      how microbial lipids position the sugar for recognition by the invariant TCR and,
      most notably, extend the range of microbes recognized by this conserved TCR to
      several clinically important bacteria.

PMID- 21892174
TI  - The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in
      dendritic cells.
AB  - The recognition of pathogenic DNA is important to the initiation of antiviral
      responses. Here we report the identification of DDX41, a member of the DEXDc
      family of helicases, as an intracellular DNA sensor in myeloid dendritic cells
      (mDCs). Knockdown of DDX41 expression by short hairpin RNA blocked the ability of
      mDCs to mount type I interferon and cytokine responses to DNA and DNA viruses.
      Overexpression of both DDX41 and the membrane-associated adaptor STING together
      had a synergistic effect in promoting Ifnb promoter activity. DDX41 bound both
      DNA and STING and localized together with STING in the cytosol. Knockdown of
      DDX41 expression blocked activation of the mitogen-activated protein kinase TBK1
      and the transcription factors NF-kappaB and IRF3 by B-form DNA. Our results
      suggest that DDX41 is an additional DNA sensor that depends on STING to sense
      pathogenic DNA.

PMID- 21892175
TI  - Human cytomegalovirus microRNA miR-US4-1 inhibits CD8(+) T cell responses by
      targeting the aminopeptidase ERAP1.
AB  - Major histocompatibility complex (MHC) class I molecules present peptides on the
      cell surface to CD8(+) T cells, which is critical for the killing of virus
      infected or transformed cells. Precursors of MHC class I-presented peptides are
      trimmed to mature epitopes by the aminopeptidase ERAP1. The US2-US11 genomic
      region of human cytomegalovirus (HCMV) is dispensable for viral replication and
      encodes three microRNAs (miRNAs). We show here that HCMV miR-US4-1 specifically
      downregulated ERAP1 expression during viral infection. Accordingly, the trimming
      of HCMV-derived peptides was inhibited, which led to less susceptibility of
      infected cells to HCMV-specific cytotoxic T lymphocytes (CTLs). Our findings
      identify a previously unknown viral miRNA-based CTL-evasion mechanism that
      targets a key step in the MHC class I antigen-processing pathway.

PMID- 21892176
TI  - Large variation of vacancy formation energies in the surface of crystalline ice.
AB  - Resolving the atomic structure of the surface of ice particles within clouds,
      over the temperature range encountered in the atmosphere and relevant to
      understanding heterogeneous catalysis on ice, remains an experimental challenge.
      By using first-principles calculations, we show that the surface of crystalline
      ice exhibits a remarkable variance in vacancy formation energies, akin to an
      amorphous material. We find vacancy formation energies as low as ~0.1-0.2 eV,
      which leads to a higher than expected vacancy concentration. Because a vacancy's
      reactivity correlates with its formation energy, ice particles may be more
      reactive than previously thought. We also show that vacancies significantly
      reduce the formation energy of neighbouring vacancies, thus facilitating pitting
      and contributing to pre-melting and quasi-liquid layer formation. These surface
      properties arise from proton disorder and the relaxation of geometric
      constraints, which suggests that other frustrated materials may possess unusual
      surface characteristics.

PMID- 21892177
TI  - Digitally tunable physicochemical coding of material composition and topography
      in continuous microfibres.
AB  - Heterotypic functional materials with compositional and topographical properties
      that vary spatiotemporally on the micro- or nanoscale are common in nature.
      However, fabricating such complex materials in the laboratory remains
      challenging. Here we describe a method to continuously create microfibres with
      tunable morphological, structural and chemical features using a microfluidic
      system consisting of a digital, programmable flow control that mimics the silk
      spinning process of spiders. With this method we fabricated hydrogel microfibres
      coded with varying chemical composition and topography along the fibre, including
      gas micro-bubbles as well as nanoporous spindle-knots and joints that enabled
      directional water collection. We also explored the potential use of the coded
      microfibres for tissue engineering applications by creating multifunctional
      microfibres with a spatially controlled co-culture of encapsulated cells.

PMID- 21892178
TI  - Gas detection by structural variations of fluorescent guest molecules in a
      flexible porous coordination polymer.
AB  - The development of a new methodology for visualizing and detecting gases is
      imperative for various applications. Here, we report a novel strategy in which
      gas molecules are detected by signals from a reporter guest that can read out a
      host structural transformation. A composite between a flexible porous
      coordination polymer and fluorescent reporter distyrylbenzene (DSB) selectively
      adsorbed CO2 over other atmospheric gases. This adsorption induced a host
      transformation, which was accompanied by conformational variations of the
      included DSB. This read-out process resulted in a critical change in DSB
      fluorescence at a specific threshold pressure. The composite shows different
      fluorescence responses to CO2 and acetylene, compounds that have similar
      physicochemical properties. Our system showed, for the first time, that
      fluorescent molecules can detect gases without any chemical interaction or energy
      transfer. The host-guest coupled transformations play a pivotal role in
      converting the gas adsorption events into detectable output signals.

PMID- 21892179
TI  - An artificial biomineral formed by incorporation of copolymer micelles in calcite
      crystals.
AB  - Biominerals exhibit morphologies, hierarchical ordering and properties that
      invariably surpass those of their synthetic counterparts. A key feature of these
      materials, which sets them apart from synthetic crystals, is their nanocomposite
      structure, which derives from intimate association of organic molecules with the
      mineral host. We here demonstrate the production of artificial biominerals where
      single crystals of calcite occlude a remarkable 13 wt% of 20 nm anionic diblock
      copolymer micelles, which act as 'pseudo-proteins'. The synthetic crystals
      exhibit analogous texture and defect structures to biogenic calcite crystals and
      are harder than pure calcite. Further, the micelles are specifically adsorbed on
      {104} faces and undergo a change in shape on incorporation within the crystal
      lattice. This system provides a unique model for understanding biomineral
      formation, giving insight into both the mechanism of occlusion of
      biomacromolecules within single crystals, and the relationship between the
      macroscopic mechanical properties of a crystal and its microscopic structure.

PMID- 21892180
TI  - A recombinant Mycobacterium smegmatis induces potent bactericidal immunity
      against Mycobacterium tuberculosis.
AB  - We report the involvement of an evolutionarily conserved set of mycobacterial
      genes, the esx-3 region, in evasion of bacterial killing by innate immunity.
      Whereas high-dose intravenous infections of mice with the rapidly growing
      mycobacterial species Mycobacterium smegmatis bearing an intact esx-3 locus were
      rapidly lethal, infection with an M. smegmatis Deltaesx-3 mutant (here designated
      as the IKE strain) was controlled and cleared by a MyD88-dependent bactericidal
      immune response. Introduction of the orthologous Mycobacterium tuberculosis esx-3
      genes into the IKE strain resulted in a strain, designated IKEPLUS, that remained
      susceptible to innate immune killing and was highly attenuated in mice but had a
      marked ability to stimulate bactericidal immunity against challenge with virulent
      M. tuberculosis. Analysis of these adaptive immune responses indicated that the
      highly protective bactericidal immunity elicited by IKEPLUS was dependent on
      CD4(+) memory T cells and involved a distinct shift in the pattern of cytokine
      responses by CD4(+) cells. Our results establish a role for the esx-3 locus in
      promoting mycobacterial virulence and also identify the IKE strain as a
      potentially powerful candidate vaccine vector for eliciting protective immunity
      to M. tuberculosis.

PMID- 21892181
TI  - Isolation and in vitro expansion of human colonic stem cells.
AB  - Here we describe the isolation of stem cells of the human colonic epithelium.
      Differential cell surface abundance of ephrin type-B receptor 2 (EPHB2) allows
      the purification of different cell types from human colon mucosa biopsies. The
      highest EPHB2 surface levels correspond to epithelial colonic cells with the
      longest telomeres and elevated expression of intestinal stem cell (ISC) marker
      genes. Moreover, using culturing conditions that recreate the ISC niche, a
      substantial proportion of EPHB2-high cells can be expanded in vitro as an
      undifferentiated and multipotent population.

PMID- 21892182
TI  - p38 MAPK-mediated regulation of Xbp1s is crucial for glucose homeostasis.
AB  - Here we show that p38 mitogen-activated protein kinase (p38 MAPK) phosphorylates
      the spliced form of X-box binding protein 1 (Xbp1s) on its Thr48 and Ser61
      residues and greatly enhances its nuclear migration in mice, whereas mutation of
      either residue to alanine substantially reduces its nuclear translocation and
      activity. We also show that p38 MAPK activity is markedly reduced in the livers
      of obese mice compared with lean mice. Further, we show that activation of p38
      MAPK by expression of constitutively active MAP kinase kinase 6 (MKK6Glu) greatly
      enhances nuclear translocation of Xbp1s, reduces endoplasmic reticulum stress and
      establishes euglycemia in severely obese and diabetic mice. Hence, our results
      define a crucial role for phosphorylation on Thr48 and Ser61 of Xbp1s in the
      maintenance of glucose homeostasis in obesity, and they suggest that p38 MAPK
      activation in the livers of obese mice could lead to a new therapeutic approach
      to the treatment of type 2 diabetes.

PMID- 21892183
TI  - Adaptive braking by Ase1 prevents overlapping microtubules from sliding
      completely apart.
AB  - Short regions of overlap between ends of antiparallel microtubules are central
      elements within bipolar microtubule arrays. Although their formation requires
      motors, recent in vitro studies demonstrated that stable overlaps cannot be
      generated by molecular motors alone. Motors either slide microtubules along each
      other until complete separation or, in the presence of opposing motors, generate
      oscillatory movements. Here, we show that Ase1, a member of the conserved
      MAP65/PRC1 family of microtubule-bundling proteins, enables the formation of
      stable antiparallel overlaps through adaptive braking of Kinesin-14-driven
      microtubule-microtubule sliding. As overlapping microtubules start to slide
      apart, Ase1 molecules become compacted in the shrinking overlap and the sliding
      velocity gradually decreases in a dose-dependent manner. Compaction is driven by
      moving microtubule ends that act as barriers to Ase1 diffusion. Quantitative
      modelling showed that the molecular off-rate of Ase1 is sufficiently low to
      enable persistent overlap stabilization over tens of minutes. The finding of
      adaptive braking demonstrates that sliding can be slowed down locally to
      stabilize overlaps at the centre of bipolar arrays, whereas sliding proceeds
      elsewhere to enable network self-organization.

PMID- 21892184
TI  - A genetically incorporated crosslinker reveals chaperone cooperation in acid
      resistance.
AB  - Acid chaperones are essential factors in preserving the protein homeostasis for
      enteric pathogens to survive in the extremely acidic mammalian stomach (pH 1-3).
      The client proteins of these chaperones remain largely unknown, primarily because
      of the exceeding difficulty of determining protein-protein interactions under low
      pH conditions. We developed a genetically encoded, highly efficient protein
      photocrosslinking probe, which enabled us to profile the in vivo substrates of a
      major acid-protection chaperone, HdeA, in Escherichia coli periplasm. Among the
      identified HdeA client proteins, the periplasmic chaperones DegP and SurA were
      initially found to be protected by HdeA at a low pH, but they subsequently
      facilitated the HdeA-mediated acid recovery of other client proteins. This
      unique, ATP-independent chaperone cooperation in the ATP-deprived E. coli
      periplasm may support the acid resistance of enteric bacteria. The crosslinker
      would be valuable in unveiling the physiological interaction partners of any
      given protein and thus their functions under normal and stress conditions.

PMID- 21892185
TI  - High-frequency transposition for determining antibacterial mode of action.
AB  - Connecting bacterial growth inhibitors to molecular targets at the whole-cell
      level is a major impediment to antibacterial development. Herein we report the
      design of a highly efficient and versatile bacteriophage-based mariner transposon
      delivery system in Staphylococcus aureus for determining inhibitor mode of
      action. Using bacteriophage-mediated delivery of concatameric minitransposon
      cassettes, we generated nonclonal transposant libraries with genome-wide
      insertion-site coverage in either laboratory or methicillin-resistant strain
      backgrounds and screened for drug resistance in situ on a single agar plate in
      one step. A gradient of gene-target expression levels, along with a
      correspondingly diverse assortment of drug-resistant phenotypes, was achieved by
      fitting the transposon cassette with a suite of outward-facing promoters. Using a
      panel of antibiotics, we demonstrate the ability to unveil not only an
      inhibitor's molecular target but also its route of cellular entry, efflux
      susceptibility and other off-target resistance mechanisms.

PMID- 21892186
TI  - Lymphadenoma of the salivary gland: clinicopathological and immunohistochemical
      analysis of 33 tumors.
AB  - Lymphadenomas (LADs) are rare salivary gland tumors. Their clinicopathologic
      characteristics and etiopathogenesis are poorly understood. We examined 33 LADs
      in 31 patients (17 women and 14 men) aged 11-79 years (median 65 years). There
      were 22 sebaceous LADs in 21 patients (9 women and 12 men) and 11 non-sebaceous
      LADs in 10 patients (8 women and 2 men). Two patients had synchronous double
      tumors. Twenty-six tumors (79%) arose in parotid, three in the neck, and two each
      in submandibular gland and oral cavity. Extraparotid tumors were seen in 2 of 21
      (10%) patients with sebaceous and 4 of 10 (40%) patients with non-sebaceous LADs.
      Seven of twenty-three (30%) patients had immunosuppressive therapy for unrelated
      diseases. The tumors were well circumscribed, encapsulated (n=28, 84%) painless
      masses, varying in size from 0.6 to 6 cm (median 2.2). The cut surfaces were gray
      tan to yellow, homogeneous and multicystic (n=24, 72%). The epithelial cells were
      basaloid, squamous and glandular, forming solid nests, cords, tubules, and cysts.
      Sebaceous differentiation was restricted to sebaceous lymphadenoma. The
      epithelial cells expressed basal cell markers (p63, 34BE12, and/or CK5/6, 18/18,
      100%) and the luminal glandular cells expressed CK7 (12/12, 100%). Myoepithelial
      cells were absent (n=10/16, 63%) or focal. The lymphoid stroma was reactive, with
      germinal centers in 28 (84%). There was no evidence of HPV (0/11), EBV (0/7), and
      HHV-8 (0/8). Malignant transformation to sebaceous and basal cell adenocarcinoma
      was seen in one patient each. None of the 11 patients with follow-up (1-8 years)
      recurred. In summary, sebaceous and non-sebaceous LADs are benign, encapsulated,
      solid and cystic tumors affecting older adults. Non-sebaceous LADs affect women
      and extraparotid sites more frequently than sebaceous LADs. Altered immune status
      may have a role in their etiopathogenesis. Multiple synchronous tumors, origin in
      buccal mucosa, and malignant transformation may rarely occur.

PMID- 21892187
TI  - Transcriptomic analysis of avian digits reveals conserved and derived digit
      identities in birds.
AB  - Morphological characters are the result of developmental gene expression. The
      identity of a character is ultimately grounded in the gene regulatory network
      directing development and thus whole-genome gene expression data can provide
      evidence about character identity. This approach has been successfully used to
      assess cell-type identity. Here we use transcriptomic data to address a long
      standing uncertainty in evolutionary biology, the identity of avian wing digits.
      Embryological evidence clearly identifies the three wing digits as developing
      from digit positions 2, 3 and 4 (ref. 6), whereas palaeontological data suggest
      that they are digits I, II and III. We compare the transcriptomes of the wing and
      foot digits and find a strong signal that unites the first wing digit with the
      first foot digit, even though the first wing digit develops from embryological
      position 2. Interestingly, our transcriptomic data of the posterior digits show a
      higher degree of differentiation among forelimb digits compared with hindlimb
      digits. These data show that in the stem lineage of birds the first digit
      underwent a translocation from digit position 1 to position 2, and further
      indicate that the posterior wing digits have unique identities contrary to any
      model of avian digit identity proposed so far.

PMID- 21892188
TI  - The structure and catalytic mechanism of a poly(ADP-ribose) glycohydrolase.
AB  - Post-translational modification of proteins by poly(ADP-ribosyl)ation regulates
      many cellular pathways that are critical for genome stability, including DNA
      repair, chromatin structure, mitosis and apoptosis. Poly(ADP-ribose) (PAR) is
      composed of repeating ADP-ribose units linked via a unique glycosidic ribose
      ribose bond, and is synthesized from NAD by PAR polymerases. PAR glycohydrolase
      (PARG) is the only protein capable of specific hydrolysis of the ribose-ribose
      bonds present in PAR chains; its deficiency leads to cell death. Here we show
      that filamentous fungi and a number of bacteria possess a divergent form of PARG
      that has all the main characteristics of the human PARG enzyme. We present the
      first PARG crystal structure (derived from the bacterium Thermomonospora
      curvata), which reveals that the PARG catalytic domain is a distant member of the
      ubiquitous ADP-ribose-binding macrodomain family. High-resolution structures of
      T. curvata PARG in complexes with ADP-ribose and the PARG inhibitor ADP-HPD,
      complemented by biochemical studies, allow us to propose a model for PAR binding
      and catalysis by PARG. The insights into the PARG structure and catalytic
      mechanism should greatly improve our understanding of how PARG activity controls
      reversible protein poly(ADP-ribosyl)ation and potentially of how the defects in
      this regulation are linked to human disease.

PMID- 21892189
TI  - The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes.
AB  - Sperm and eggs carry distinctive epigenetic modifications that are adjusted by
      reprogramming after fertilization. The paternal genome in a zygote undergoes
      active DNA demethylation before the first mitosis. The biological significance
      and mechanisms of this paternal epigenome remodelling have remained unclear. Here
      we report that, within mouse zygotes, oxidation of 5-methylcytosine (5mC) occurs
      on the paternal genome, changing 5mC into 5-hydroxymethylcytosine (5hmC).
      Furthermore, we demonstrate that the dioxygenase Tet3 (ref. 5) is enriched
      specifically in the male pronucleus. In Tet3-deficient zygotes from conditional
      knockout mice, paternal-genome conversion of 5mC into 5hmC fails to occur and the
      level of 5mC remains constant. Deficiency of Tet3 also impedes the demethylation
      process of the paternal Oct4 and Nanog genes and delays the subsequent activation
      of a paternally derived Oct4 transgene in early embryos. Female mice depleted of
      Tet3 in the germ line show severely reduced fecundity and their heterozygous
      mutant offspring lacking maternal Tet3 suffer an increased incidence of
      developmental failure. Oocytes lacking Tet3 also seem to have a reduced ability
      to reprogram the injected nuclei from somatic cells. Therefore, Tet3-mediated DNA
      hydroxylation is involved in epigenetic reprogramming of the zygotic paternal DNA
      following natural fertilization and may also contribute to somatic cell nuclear
      reprogramming during animal cloning.

PMID- 21892190
TI  - Phylogenomics reveals deep molluscan relationships.
AB  - Evolutionary relationships among the eight major lineages of Mollusca have
      remained unresolved despite their diversity and importance. Previous
      investigations of molluscan phylogeny, based primarily on nuclear ribosomal gene
      sequences or morphological data, have been unsuccessful at elucidating these
      relationships. Recently, phylogenomic studies using dozens to hundreds of genes
      have greatly improved our understanding of deep animal relationships. However,
      limited genomic resources spanning molluscan diversity has prevented use of a
      phylogenomic approach. Here we use transcriptome and genome data from all major
      lineages (except Monoplacophora) and recover a well-supported topology for
      Mollusca. Our results strongly support the Aculifera hypothesis placing
      Polyplacophora (chitons) in a clade with a monophyletic Aplacophora (worm-like
      molluscs). Additionally, within Conchifera, a sister-taxon relationship between
      Gastropoda and Bivalvia is supported. This grouping has received little
      consideration and contains most (>95%) molluscan species. Thus we propose the
      node-based name Pleistomollusca. In light of these results, we examined the
      evolution of morphological characters and found support for advanced
      cephalization and shells as possibly having multiple origins within Mollusca.

PMID- 21892192
TI  - Effects of the histamine H(1) receptor antagonist hydroxyzine on hERG K(+)
      channels and cardiac action potential duration.
AB  - AIM: To investigate the effects of hydroxyzine on human ether-a-go-go-related
      gene (hERG) channels to determine the electrolphysiological basis for its
      proarrhythmic effects. METHODS: hERG channels were expressed in Xenopus oocytes
      and HEK293 cells, and the effects of hydroxyzine on the channels were examined
      using two-microelectrode voltage-clamp and patch-clamp techniques, respectively.
      The effects of hydroxyzine on action potential duration were examined in guinea
      pig ventricular myocytes using current clamp. RESULTS: Hydroxyzine (0.2 and 2
      MUmol/L) significantly increased the action potential duration at 90%
      repolarization (APD(90)) in both concentration- and time-dependent manners.
      Hydroxyzine (0.03-3 MUmol/L) blocked both the steady-state and tail hERG
      currents. The block was voltage-dependent, and the values of IC(50) for blocking
      the steady-state and tail currents at +20 mV was 0.18+/-0.02 MUmol/L and 0.16+/
      0.01 MUmol/L, respectively, in HEK293 cells. Hydroxyzine (5 MUmol/L) affected
      both the activated and the inactivated states of the channels, but not the closed
      state. The S6 domain mutation Y652A attenuated the blocking of hERG current by ~6
      fold. CONCLUSION: The results suggest that hydroxyzine could block hERG channels
      and prolong APD. The tyrosine at position 652 in the channel may be responsible
      for the proarrhythmic effects of hydroxyzine.

PMID- 21892193
TI  - Interaction between Galpha12 and Galpha13 protein subunits and dopamine receptors
      in renal proximal tubules.

PMID- 21892191
TI  - Antidiabetic actions of a non-agonist PPARgamma ligand blocking Cdk5-mediated
      phosphorylation.
AB  - PPARgamma is the functioning receptor for the thiazolidinedione (TZD) class of
      antidiabetes drugs including rosiglitazone and pioglitazone. These drugs are full
      classical agonists for this nuclear receptor, but recent data have shown that
      many PPARgamma-based drugs have a separate biochemical activity, blocking the
      obesity-linked phosphorylation of PPARgamma by Cdk5. Here we describe novel
      synthetic compounds that have a unique mode of binding to PPARgamma, completely
      lack classical transcriptional agonism and block the Cdk5-mediated
      phosphorylation in cultured adipocytes and in insulin-resistant mice. Moreover,
      one such compound, SR1664, has potent antidiabetic activity while not causing the
      fluid retention and weight gain that are serious side effects of many of the
      PPARgamma drugs. Unlike TZDs, SR1664 also does not interfere with bone formation
      in culture. These data illustrate that new classes of antidiabetes drugs can be
      developed by specifically targeting the Cdk5-mediated phosphorylation of
      PPARgamma.

PMID- 21892195
TI  - Preparation and immunogenicity of tag-free recombinant human eppin.
AB  - Human epididymal protease inhibitor (eppin) may be effective as a male
      contraceptive vaccine. In a number of studies, eppin with an engineered His(6)
      tag has been produced using prokaryotic expression systems. For production of
      pharmaceutical-grade proteins for human use, however, the His(6)-tag must be
      removed. This study describes a method for producing recombinant human eppin
      without a His(6)-tag. We constructed plasmid pET28a (+)-His(6)-tobacco etch virus
      (TEV)-eppin for expression in Escherichia coli. After purification and refolding,
      the fusion protein His(6)-TEV-eppin was digested with TEV protease to remove the
      His(6)-tag and was further purified by NTA-Ni(2+) affinity chromatography. Using
      this procedure, 2 mg of eppin without a His(6)-tag was isolated from 1 l of
      culture with a purity of >95%. The immunogenicity of the eppin was characterized
      using male Balb/c mice.

PMID- 21892196
TI  - A systematic review of the effects and mechanisms of preoperative 5alpha
      reductase inhibitors on intraoperative haemorrhage during surgery for benign
      prostatic hyperplasia.
AB  - 5alpha-reductase inhibitors (5alpha-RIs), including finasteride and dutasteride,
      are commonly used medical therapies for benign prostatic hyperplasia (BPH). Many
      studies reported that preoperative 5alpha-RI had impact on intraoperative
      haemorrhage during surgery for BPH, but it was still in controversial. So, we
      conducted a systematic review of the effects and mechanisms of 5alpha-RIs on
      intraoperative bleeding for BPH. MEDLINE, EMBASE, the Cochrane Controlled Trail
      Register of Controlled Trials and the reference lists of retrieved studies were
      searched in the analysis. Sixteen publications involving 15 different randomized
      controlled trials (RCTs) and a total of 1156 patients were used in the analysis,
      including 10 RCTs for finasteride and five RCTs for dutasteride. We found that
      preoperative finasteride treatment decreases microvessel density (MVD) in
      resected prostate specimens. Total blood loss, blood loss per gram of resected
      prostate tissue and decreases in haemoglobin were all greatly reduced in the
      finasteride group as compared to controls. Dutasteride appeared to have no effect
      on bleeding. This meta-analysis shows that preoperative finasteride treatment
      could decrease intraoperative haemorrhage during surgery for BPH. Preoperative
      dutasteride had no effect on intraoperative haemorrhage, but further high-quality
      prospective studies are still needed to confirm this observation.

PMID- 21892197
TI  - Association of two polymorphisms within and near SOCS3 gene with obesity in three
      nationalities in Xinjiang province of China.
AB  - AIM: SOCS3 gene plays an important role in the pathogenesis of obesity in animal
      models, but the data from human studies are relatively limited. To address this
      issue, a genetic association analysis on nationalities with different genetic
      background living in the similar environmental conditions was performed. METHODS:
      Two thousand seven hundred eleven subjects were randomly recruited from the
      Kazakh, Uygur and Han nationalities in Xinjiang of China. SNP polymorphisms
      rs4969168 and rs9892622 within or near the SOCS3 gene were genotyped using TaqMan
      MGBTM assay. Association study between the two polymorphisms and obesity-related
      traits (body mass index [BMI]; waist-to-hip ratio [WHR]; weight; height, waist,
      and hip measurements) was conducted. RESULTS: Significant association was found
      between rs4969168 and the obesity-related traits, including BMI (25.32 +/- 3.49
      kg/m(2) for AA, 24.60 +/- 3.70 kg/m(2) for AG, 24.39 +/- 3.42 kg/m(2) for GG,
      P=0.042), weight (65.58 +/- 11.42 kg for AA, 63.50 +/- 11.30 kg for AG, 62.00 +/-
      10.78 kg for GG, P=0.011) in the Han nationality, but not in the Kazakh or Uygur
      nationalities. Rs9892622 was significantly associated with BMI, WHR, and WAIST in
      the Uygur males. Rs9892622 was also associated with BMI in Kazakh males. Linear
      regression analysis verified the above findings. However, neither of the two
      polymorphisms was associated with obesity-related traits in the total population.
      CONCLUSION: The polymorphism rs4969168 within or near the SOCS3 gene has a
      significant effect in the Han nationality, while rs9892622 was associated with
      obesity in Uygur and Kazakh nationalities in Xinjiang of China.

PMID- 21892198
TI  - Genetic polymorphisms in Kawasaki disease.
AB  - Kawasaki disease (KD) is an acute febrile systemic vasculitis, and the cause of
      KD is not well understood. It is likely due to multiple interactions between
      genes and environmental factors. The development of genetic association and
      genome-wide association studies (GWAS) has opened an avenue to better
      understanding the molecular mechanisms underlying KD. A novel ITPKC signaling
      pathway was recently found to be responsible for the susceptibility to KD.
      Furthermore, the GWAS demonstrated the functionally related susceptibility loci
      for KD in the Caucasian population. In the last decade, the identification of
      several genomic regions linked to the pathogenesis of KD has made a major
      breakthrough in understanding the genetics of KD. This review will focus on
      genetic polymorphisms associated with KD and describe some of the possible
      clinical implications and molecular mechanisms that can be used to explain how
      genetic variants regulate the pathogenesis in KD.

PMID- 21892199
TI  - Platonin inhibited PDGF-BB-induced proliferation of rat vascular smooth muscle
      cells via JNK1/2-dependent signaling.
AB  - AIM: To examine the inhibitory actions of the immunoregulator platonin against
      proliferation of rat vascular smooth muscle cells (VSMCs). METHODS: VSMCs were
      prepared from the thoracic aortas of male Wistar rats. Cell proliferation was
      examined using MTT assays. Cell cycles were analyzed using flow cytometry. c-Jun
      N-terminal kinase (JNK)1/2, extracellular signal-regulated kinase (ERK)1/2, AKT,
      and c-Jun phosphorylation or p27 expression were detected using immunoblotting.
      RESULTS: Pretreatment with platonin (1-5 MUmol/L) significantly suppressed VSMC
      proliferation stimulated by PDGF-BB (10 ng/mL) or 10% fetal bovine serum (FBS),
      and arrested cell cycle progression in the S and G(2)/M phases. The same
      concentrations of platonin significantly inhibited the phosphorylation of JNK1/2
      but not ERK1/2 or AKT in VSMCs stimulated by PDGF-BB. Furthermore, platonin also
      attenuated c-Jun phosphorylation and markedly reversed the down-regulation of p27
      expression after PDGF-BB stimulation. CONCLUSION: Platonin inhibited VSMC
      proliferation, possibly via inhibiting phosphorylation of JNK1/2 and c-Jun, and
      reversal of p27 down-regulation, thereby leading to cell cycle arrest at the S
      and G(2)/M phases. Thus, platonin may represent a novel approach for lowering the
      risk of abnormal VSMC proliferation and related vascular diseases.

PMID- 21892200
TI  - Modulation of pharmacokinetics of theophylline by antofloxacin, a novel 8-amino
      fluoroquinolone, in humans.
AB  - AIM: To evaluate the pharmacokinetic interactions between theophylline and
      antofloxacin in vivo and in vitro. METHODS: A randomized, 5-day treatment and 3
      way crossover design was documented in 12 healthy subjects. The subjects were
      orally administered with antofloxacin (400 mg on d 1 and 200 mg on d 2 to 5),
      theophylline (100 mg twice a day and morning dose 200 mg on d 1 and 5), or
      theophylline plus antofloxacin. The plasma and urinary pharmacokinetics of
      antofloxacin and theophylline were characterized after the first and last dose.
      The effect of antofloxacin on theophylline metabolism was also investigated in
      pooled human liver microsomes. RESULTS: The 5-day treatment with antofloxacin
      significantly increased the area of the plasma concentration-time curve and peak
      plasma concentration of theophylline, accompanied by a decrease in the excretion
      of theophylline metabolites. On the contrary, theophylline did not affect the
      pharmacokinetics of antofloxacin. In vitro studies using pooled human hepatic
      microsomes demonstrated that antofloxacin was a weak reversible and mechanism
      based inhibitor of CYP1A2. The clinical interaction between theophylline and
      antofloxacin was further validated by the in vitro results. CONCLUSION: The
      results showed that antofloxacin increases the plasma theophylline concentration,
      partly by acting as a mechanism-based inhibitor of CYP1A2.

PMID- 21892201
TI  - Comparison between cerebral state index and bispectral index as measures of
      electroencephalographic effects of sevoflurane using combined sigmoidal E(max)
      model.
AB  - AIM: The cerebral state index (CSI) was recently introduced as an
      electroencephalographic monitor for measuring the depth of anesthesia. We
      compared the performance of CSI to the bispectral index (BIS) as
      electroencephalographic measures of sevoflurane effect using two combined
      sigmoidal E(max) models. METHODS: Twenty adult patients scheduled for laparotomy
      were studied. After induction of general anesthesia, sevoflurane concentrations
      were progressively increased and then decreased over 70 min. An analysis of the
      BIS and CSI with the sevoflurane effect-site concentration was conducted using
      two combined sigmoidal E(max) models. RESULTS: The BIS and CSI decreased over the
      initial concentration range of sevoflurane and then reached a plateau in most
      patients. A further increase in sevoflurane concentration produced a secondary
      plateau in the pharmacodynamic response. The CSI was more strongly correlated
      with effect-site sevoflurane concentration (R(2)=0.95+/-0.04) than the BIS was
      (R(2)=0.87+/-0.07) (P<0.05). The individual E(max) and C(eff50) (effect-site
      concentration associated with 50% decrease from baseline to plateau) values for
      the upper and lower plateaus were significantly greater for BIS (12.7+/-7.3,
      1.6+/-0.4, and 4.2+/-0.5, respectively) than for CSI (3.4+/-2.2, 1.2+/-0.4, and
      3.8+/-0.5, respectively) (P<0.05). The remaining pharmacodynamic parameters for
      the BIS and CSI were similar. CONCLUSION: The overall performance of the BIS and
      CSI during sevoflurane anesthesia was similar despite major differences in their
      algorithms. However, the CSI was more consistent and more sensitive to changes in
      sevoflurane concentration, whereas the measured BIS seemed to respond faster. The
      newly developed combined E(max) model adequately described the clinical data,
      including the pharmacodynamic plateau.

PMID- 21892202
TI  - Reactive oxygen species contribute to oridonin-induced apoptosis and autophagy in
      human cervical carcinoma HeLa cells.
AB  - AIM: To investigate the role of reactive oxygen species (ROS) in oridonin-induced
      apoptosis and autophagy in HeLa cells. METHODS: The cell viability was measured
      using MTT assay. Morphological changes of apoptosis and autophagy were examined
      using Hoechst 33258 staining and monodansylcadaverine (MDC) staining,
      respectively. The mitochondrial membrane potential (DeltaPsim) was measured using
      fluorescent dye rhodamine 123. DCF-induced fluorescence was used to measure the
      intracellular ROS level. Protein expression was examined using Western blot.
      RESULTS: Treatment of HeLa cells with oridonin (20-160 MUmol/L) inhibited the
      cell growth in time- and concentration-dependent manners. The cells treated with
      oridonin (80 MUmol/L) for 24 h displayed marked DNA fragmentation and MDC
      positive autophagosomes. In the presence of the specific autophagy inhibitor 3-MA
      (2 mmol/L), the oridonin-induced apoptosis was significantly enhanced. Treatment
      of HeLa cells with oridonin (20-120 MUmol/L) induced intracellular ROS generation
      in a concentration-dependent manner. In the presence of the ROS scavenger NAC (5
      mmol/L), the oridinin-induced ROS generation was markedly reduced. NAC (5 mmol/L)
      or non-thiol antioxidant catalase (1000 U/mL) significantly reduced the oridonin
      induced inhibition of cell growth and apoptosis. Furthermore, oridonin
      significantly reduced DeltaPsim, which was blocked by NAC. Oridonin markedly
      increased Bax expression in mitochondria, and decreased Bcl-2 expression in both
      the cytosol and mitochondria. Oridonin also markedly increased the
      phosphorylation of Bcl-2 in the cytosol. All the effects were blocked by NAC.
      Oridonin increased the levels of caspase-3 and caspase-8, and decreased the
      expression of pro-caspase 3 and pro-caspase 9, which were blocked by NAC.
      CONCLUSION: ROS plays a critical role in oridonin-induced apoptosis and
      autophagy.

PMID- 21892203
TI  - Cytokines: Structuring the type I IFN response.

PMID- 21892204
TI  - Molecular mechanisms of cisplatin resistance.
AB  - Platinum-based drugs, and in particular cis-diamminedichloroplatinum(II) (best
      known as cisplatin), are employed for the treatment of a wide array of solid
      malignancies, including testicular, ovarian, head and neck, colorectal, bladder
      and lung cancers. Cisplatin exerts anticancer effects via multiple mechanisms,
      yet its most prominent (and best understood) mode of action involves the
      generation of DNA lesions followed by the activation of the DNA damage response
      and the induction of mitochondrial apoptosis. Despite a consistent rate of
      initial responses, cisplatin treatment often results in the development of
      chemoresistance, leading to therapeutic failure. An intense research has been
      conducted during the past 30 years and several mechanisms that account for the
      cisplatin-resistant phenotype of tumor cells have been described. Here, we
      provide a systematic discussion of these mechanism by classifying them in
      alterations (1) that involve steps preceding the binding of cisplatin to DNA (pre
      target resistance), (2) that directly relate to DNA-cisplatin adducts (on-target
      resistance), (3) concerning the lethal signaling pathway(s) elicited by cisplatin
      mediated DNA damage (post-target resistance) and (4) affecting molecular
      circuitries that do not present obvious links with cisplatin-elicited signals
      (off-target resistance). As in some clinical settings cisplatin constitutes the
      major therapeutic option, the development of chemosensitization strategies
      constitute a goal with important clinical implications.

PMID- 21892205
TI  - Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates human schwannoma
      proliferation, adhesion and survival.
AB  - Merlin is a tumour suppressor involved in the development of a variety of tumours
      including mesotheliomas. Neurofibromatosis type 2 (NF2), a dominantly inherited
      tumour disease, is also caused by loss of merlin. NF2 patients suffer from
      multiple genetically well-defined tumours, schwannomas are most frequent among
      those. Using our in vitro model for human schwannoma, we found that schwannoma
      cells display enhanced proliferation because of the overexpression/activation of
      platelet-derived growth factor receptor and ErbB2/3, increased cell-matrix
      adhesion because of the overexpression of integrins, and decreased apoptosis.
      Mechanisms underlying schwannomas basal proliferation and cell-matrix adhesion
      are not understood. Here, we investigated insulin-like growth factor-binding
      protein-1 (IGFBP-1), which is expressed and released from central nervous system
      tumours and strongly overexpressed in schwannoma at the mRNA level. IGFBP-1 acts
      via beta1-integrin and focal-adhesion-kinase (FAK), which are strongly
      overexpressed and basally activated in schwannoma. Using short hairpin RNA
      knockdown, small inhibitors and recombinant IGFBP-1, we demonstrate that
      schwannoma cells, in contrast to Schwann cells, release IGFBP-1 that activates
      the Src/FAK pathway, via integrin beta1, potentiating schwannoma's proliferation
      and cell-matrix adhesion. We show that FAK localizes to the nucleus and Src
      triggers IGFBP-1 production. Further, we observed downregulation of the tumour
      suppressor phosphatase and tensin homolog in schwannoma cells leading to
      increased activity of anti-apoptotic AKT. Thus, IGFBP-1/integrin beta1/Src/FAK
      pathway has a crucial role in merlin-related tumourigenesis and therefore
      represents an important therapeutic target in the treatment of merlin-deficient
      tumours.

PMID- 21892206
TI  - Different phenotypic consequences of simultaneous versus stepwise Apc loss.
AB  - APC is considered a gatekeeper for colorectal cancer (CRC). Cells with
      heterozygous APC mutations have altered expression profiles suggesting that the
      first APC hit may help set the stage for subsequent transformation. Therefore, we
      measured transformation efficiency following what we have designated as
      'simultaneous' versus 'stepwise' Apc loss. We combined a conditional Apc allele
      (Apc(CKO)) with a Cre reporter gene and an out-of-frame Cre allele (Pms2(cre))
      that stochastically becomes functional by a frameshift mutation in single cells.
      Loss of one Apc allele (Apc(CKO/+)) had little consequence, whereas simultaneous
      loss of both Apc alleles (Apc(CKO/CKO)) resulted in increased clonal expansion
      (crypt fission), consistent with the gatekeeper function of Apc. Interestingly,
      our analyses showed that most of the Apc-deficient crypts in Apc(CKO/CKO) mice
      appeared normal, with morphological transformation, including beta-catenin
      deregulation, occurring in only 17% of such crypts. To determine whether
      transformation efficiency was different following stepwise Apc loss, we combined
      Apc(CKO) with a germline mutant allele, either Apc(Min) or Apc(1638N).
      Transformation efficiency following stepwise Apc loss (Apc(Min/CKO) or
      Apc(1638N/CKO)) was increased five-fold and essentially all of the Apc-deficient
      cells were dysplastic. In summary, our data suggest that the gatekeeper function
      of Apc consists of two roles, clonal expansion and morphological transformation,
      because simultaneous Apc loss frequently leads to occult clonal expansion without
      morphological transformation, whereas stepwise Apc loss more often results in
      visible neoplasia. Finally, that Apc-deficient cells in certain scenarios can
      retain a normal phenotype is unexpected and may have clinical implications for
      surveillance strategies to prevent CRC.

PMID- 21892207
TI  - c-Abl and Arg are activated in human primary melanomas, promote melanoma cell
      invasion via distinct pathways, and drive metastatic progression.
AB  - Despite 35 years of clinical trials, there is little improvement in 1-year
      survival rates for patients with metastatic melanoma, and the disease is
      essentially untreatable if not cured surgically. The paucity of chemotherapeutic
      agents that are effective for treating metastatic melanoma indicates a dire need
      to develop new therapies. Here, we found a previously unrecognized role for c-Abl
      and Arg in melanoma progression. We demonstrate that the kinase activities of c
      Abl and Arg are elevated in primary melanomas (60%), in a subset of benign nevi
      (33%) and in some human melanoma cell lines. Using siRNA and pharmacological
      approaches, we show that c-Abl/Arg activation is functionally relevant because it
      is requiredfor melanoma cell proliferation, survival and invasion. Significantly,
      we identify the mechanism by which activated c-Abl promotes melanoma invasion by
      showing that it transcriptionally upregulates matrix metalloproteinase-1 (MMP-1),
      and using rescue approaches we demonstrate that c-Abl promotes invasion through a
      STAT3 -> MMP-1 pathway. Additionally, we show that c-Abl and Arg are not merely
      redundant, as active Arg drives invasion in a STAT3-independent manner, and
      upregulates MMP-3 and MT1-MMP, in addition to MMP-1. Most importantly, c-Abl and
      Arg not only promote in vitro processes important for melanoma progression, but
      also promote metastasis in vivo, as inhibition of c-Abl/Arg kinase activity with
      the c-Abl/Arg inhibitor, nilotinib, dramatically inhibits metastasis in a mouse
      model. Taken together, these data identify c-Abl and Arg as critical, novel, drug
      targets in metastatic melanoma, and indicate that nilotinib may be useful in
      preventing metastasis in patients with melanomas harboring active c-Abl and Arg.

PMID- 21892208
TI  - GATA3 inhibits lysyl oxidase-mediated metastases of human basal triple-negative
      breast cancer cells.
AB  - Discovery of mechanisms that impede the aggressive and metastatic phenotype of
      human basal triple-negative-type breast cancers (BTNBCs) could provide novel
      targets for therapy for this form of breast cancer that has a relatively poor
      prognosis. Previous studies have demonstrated that expression of GATA3, the
      master transcriptional regulator of mammary luminal differentiation, can reduce
      the tumorigenicity and metastatic propensity of the human BTNBC MDA-MB-231 cell
      line (MB231), although the mechanism for reduced metastases was not elucidated.
      We demonstrate through gene expression profiling that GATA3 expression in 231
      cells resulted in the dramatic reduction in the expression of lysyl oxidase
      (LOX), a metastasis-promoting, matrix-remodeling protein, in part, through
      methylation of the LOX promoter. Suppression of LOX expression by GATA3 was
      further confirmed in the BTNBC Hs578T cell line. Conversely, reduction of GATA3
      expression by small interfering RNA in luminal BT474 cells increased LOX
      expression. Reconstitution of LOX expression in 231-GATA3 cells restored
      metastatic propensity. A strong inverse association between LOX and GATA3
      expression was confirmed in a panel of 51 human breast cancer cell lines.
      Similarly, human breast cancer microarray data demonstrated that high LOX/low
      GATA3 expression is associated with the BTNBC subtype of breast cancer and poor
      patient prognosis. Expression of GATA3 reprograms BTNBCs to a less aggressive
      phenotype and inhibits a major mechanism of metastasis through inhibition of LOX.
      Induction of GATA3 in BTNBC cells or novel approaches that inhibit LOX expression
      or activity could be important strategies for treating BTNBCs.

PMID- 21892209
TI  - An integrated genomic approach identifies ARID1A as a candidate tumor-suppressor
      gene in breast cancer.
AB  - Tumor-suppressor genes (TSGs) have been classically defined as genes whose loss
      of function in tumor cells contributes to the formation and/or maintenance of the
      tumor phenotype. TSGs containing nonsense mutations may not be expressed because
      of nonsense-mediated RNA decay (NMD). We combined inhibition of the NMD process,
      which clears transcripts that contain nonsense mutations, with the application of
      high-density single-nucleotide polymorphism arrays analysis to discriminate
      allelic content in order to identify candidate TSGs in five breast cancer cell
      lines. We identified ARID1A as a target of NMD in the T47D breast cancer cell
      line, likely as a consequence of a mutation in exon-9, which introduces a
      premature stop codon at position Q944. ARID1A encodes a human homolog of yeast
      SWI1, which is an integral member of the hSWI/SNF complex, an ATP-dependent,
      chromatin-remodeling, multiple-subunit enzyme. Although we did not find any
      somatic mutations in 11 breast tumors, which show DNA copy-number loss at the
      1p36 locus adjacent to ARID1A, we show that low ARID1A RNA or nuclear protein
      expression is associated with more aggressive breast cancer phenotypes, such as
      high tumor grade, in two independent cohorts of over 200 human breast cancer
      cases each. We also found that low ARID1A nuclear expression becomes more
      prevalent during the later stages of breast tumor progression. Finally, we found
      that ARID1A re-expression in the T47D cell line results in significant inhibition
      of colony formation in soft agar. These results suggest that ARID1A may be a
      candidate TSG in breast cancer.

PMID- 21892210
TI  - Disabling the mitotic spindle and tumor growth by targeting a cavity-induced
      allosteric site of survivin.
AB  - Survivin is a member of the inhibitor of apoptosis protein family and has an
      essential role in mitosis. Survivin is overexpressed in a large variety of human
      cancers and represents an attractive target for cancer therapy. Epidermal growth
      factor receptor and Her/neu-transformed human tumors in particular exhibit high
      levels of survivin. The survivin protein forms dimers through a conserved region
      that is critical for subcellular localization and biological functions of the
      protein. We identified small molecules that target a specific cavity adjacent to
      the survivin dimerization surfaces. S12, a lead compound identified in the
      screen, can bind to the survivin protein at the intended target site. Moreover,
      S12 alters spindle formation, causing mitotic arrest and cell death, and inhibits
      tumor growth in vitro and in vivo. Cell death occurs in premetaphase stage
      following mitotic arrest and is not a consequence of general toxicity. Thus, the
      study validates a novel therapeutic target site in the survivin protein and
      provides a promising strategy to develop a new class of therapeutic small
      molecules for the treatment of human cancers.

PMID- 21892211
TI  - Silencing of Kruppel-like factor 2 by the histone methyltransferase EZH2 in human
      cancer.
AB  - The Kruppel-like factor (KLF) proteins are multitasked transcriptional regulators
      with an expanding tumor suppressor function. KLF2 is one of the prominent members
      of the family because of its diminished expression in malignancies and its growth
      inhibitory, pro-apoptotic and anti-angiogenic roles. In this study, we show that
      epigenetic silencing of KLF2 occurs in cancer cells through direct
      transcriptional repression mediated by the Polycomb group protein Enhancer of
      Zeste Homolog 2 (EZH2). Binding of EZH2 to the 5'-end of KLF2 is also associated
      with a gain of trimethylated lysine 27 histone H3 and a depletion of
      phosphorylated serine 2 of RNA polymerase. Upon depletion of EZH2 by RNA
      interference, short hairpin RNA or use of the small molecule 3-Deazaneplanocin A,
      the expression of KLF2 was restored. The transfection of KLF2 in cells with EZH2
      associated silencing showed a significant anti-tumoral effect, both in culture
      and in xenografted nude mice. In this last setting, KLF2 transfection was also
      associated with decreased dissemination and lower mortality rate. In EZH2
      depleted cells, which characteristically have lower tumorigenicity, the induction
      of KLF2 depletion 'rescued' partially the oncogenic phenotype, suggesting that
      KLF2 repression has an important role in EZH2 oncogenesis. Most importantly, the
      translation of the described results to human primary samples demonstrated that
      patients with prostate or breast tumors with low levels of KLF2 and high
      expression of EZH2 had a shorter overall survival.

PMID- 21892212
TI  - IgG antibodies to ATG early after pediatric hematopoietic SCT increase the risk
      of acute GVHD.
AB  - Anti-thymocyte globulin (ATG), raised in rabbits, is frequently used in
      allogeneic hematopoietic SCT (HSCT), to prevent graft rejection and acute GVHD.
      In solid organ transplant patients, antibodies to rabbit IgG result in an
      enhanced clearance of ATG. The occurrence of such antibodies in HSCT recipients
      and their clinical impact is unknown. Concentrations of ATG and anti-ATG
      antibodies were measured in 72 pediatric HSCT recipients treated with ATG as part
      of the conditioning. Anti-ATG antibodies were detected in 20 children (28%), all
      transplanted with a non-depleted graft. IgG anti-ATG, alone or combined with IgM
      and/or IgA anti-ATG, appeared in 10 children. Four patients developed IgG anti
      ATG antibodies early (before day 22) post-HSCT. They had steep drops in ATG
      levels and showed rapid T-cell recovery, which was associated with a
      significantly increased risk of acute GVHD. In six patients IgG anti-ATG
      responses occurred later (range 28-46 days) after HSCT without an increased risk
      of GVHD. A total of 10 children only mounted an IgM (and IgA) anti-ATG response,
      which was without major impact on ATG levels. These results indicate that early
      development of IgG anti-ATG antibodies has a major impact on acute GVHD. Routine
      analysis ATG/anti-ATG Ab measurement should be considered.

PMID- 21892213
TI  - Thorough work-up and new diagnostic criteria needed for CJD.

PMID- 21892214
TI  - Stroke: Consensus on evidence-based implementation of early supported discharge.

PMID- 21892215
TI  - [The AVERROES study].

PMID- 21892217
TI  - [Inferior vena cava filters: any indications anymore?].
AB  - Inferior vena cava filters (IVCFs) are metal alloy devices that mechanically trap
      fragmented thromboemboli from the deep leg veins en route to the pulmonary
      circulation. Filters are introduced (and in the case of retrievable filters,
      removed) percutaneously. Although their deployment seems of theoretical benefit,
      their clinical efficacy and adverse event profile are unclear because there are
      very few controlled and randomized data. IVCFs are most frequently used in
      patients with contraindications to anticoagulation and in anticoagulated patients
      with recurrent pulmonary embolism, but few data are available in the literature
      about their efficacy. The indications for filters are based largely on custom,
      historical practice patterns and physician preferences, and their use is
      increasing: more trials are needed to confirm their benefit and accurately assess
      their safety. The care of patients with or at risk of venous thromboembolism is
      as variable and challenging as the range of patients who suffer from venous
      thrombosis. Careful, individualized decision regarding IVCF placement will be
      required for many years as we strive to learn more about these devices.

PMID- 21892216
TI  - [Thromboembolic prophylaxis 2011: is warfarin on the wane?].
AB  - Warfarin has been the effective treatment in the prophylaxis of cardioembolism,
      in particular in patients with atrial fibrillation, for more than 50 years.
      Nevertheless, many patients with atrial fibrillation are not currently treated
      because of the numerous limits of oral anticoagulation and in those treated the
      quality of anticoagulation is often poor. Novel oral anticoagulant drugs, the
      direct thrombin antagonist dabigatran and factor Xa inhibitors such as
      rivaroxaban, apixaban, edoxaban, and betrixaban are more predictable and
      convenient anticoagulants in comparison with warfarin, mainly because of the non
      requirement of regular laboratory monitoring and dose adjustments. Current data
      from phase III clinical trials are available for dabigatran, rivaroxaban and
      apixaban, which show to be at least noninferior in efficacy to warfarin for the
      prevention of stroke in patients with atrial fibrillation. This review focuses on
      the potential of novel anticoagulants to replace warfarin in patients with atrial
      fibrillation. Also the place in therapy and the potential limitations of the new
      agents in clinical practice represent important issues to be considered. The
      promise of new oral anticoagulants gives us the hope that warfarin will finally
      be replaced in a near future, but more importantly that anticoagulant
      undertreatment of atrial fibrillation will be partially overcome.

PMID- 21892218
TI  - [Treatment of acute high-risk pulmonary embolism].
AB  - At present, high-risk pulmonary embolism represents a cardiovascular emergency
      burdened with high in-hospital mortality and characterized by acute right
      ventricular dysfunction and hemodynamic impairment. In addition to circulatory
      support and anticoagulation, thrombolytic therapy has become the cornerstone of
      the treatment in patients presenting with this condition. Despite the
      recommendations, a consistent proportion of patients does not currently receive
      thrombolytic therapy. Although performed in a limited number of patients,
      transcatheter and surgical embolectomy procedures are an alternative or
      synergistic therapeutic strategy to thrombolysis, enabling a prompt resolution of
      right ventricular volume overload. In this review, data from the literature are
      discussed with the aim of defining an algorithm for the treatment of high-risk
      patients.

PMID- 21892219
TI  - [Differences among beta-blockers for the treatment of patients with heart failure
      and chronic obstructive pulmonary disease].
AB  - Although current guidelines support the use of beta-blockers (BB) in all patients
      with symptomatic heart failure (HF) and left ventricular systolic dysfunction,
      unless contraindicated or not tolerated, they are still underused, especially in
      patients with chronic obstructive pulmonary disease (COPD). BB are associated
      with a potential risk for lung function decline and airway hyperresponsiveness,
      and reluctance still exists to prescribe these agents in COPD patients. However,
      a large body of evidence indicates that these patients tolerate well selective
      beta-blockade, and BB should not be denied to HF patients with concomitant COPD.
      Current guidelines and recent reports recommend the use of selective BB in all
      patients with stable COPD and irreversible airway obstruction, to be administered
      at the lowest dose and at a low titration rate. Close monitoring of lung function
      by spirometry is strongly encouraged to guide and enhance a safe BB use in
      everyday practice. Pneumologists and cardiologists should develop shared
      strategies with the aim to implement selective BB therapy in clinical practice
      and improve the prognosis of both HF and COPD.

PMID- 21892220
TI  - [Praise for a conscious ethical choice].

PMID- 21892221
TI  - [Spinal cord stimulation for refractory chronic angina pectoris: 100 patients
      treated in our 12-year experience].
AB  - BACKGROUND: The aim of this study was to evaluate the quality of life (QoL)
      benefit of patients with chronic refractory angina treated with spinal cord
      stimulation (SCS) in our experience. METHODS: Between February 1998 and August
      2010, 100 patients with chronic refractory angina who could not benefit from
      myocardial revascularization underwent SCS at the San Raffaele Scientific
      Institute of Milan (Italy). All patients were prospectively followed up at our
      outpatient clinic. The Spitzer index was used to evaluate QoL of patients before
      the procedure and at follow-up. RESULTS: Mean age was 66 +/- 8 years (range 46
      79). Ninety-four patients (94%) were in CCS class III-IV (mean CCS class 3.5 +/-
      0.1) and 62 patients (62%) were in NYHA class III-IV (mean NYHA class 2.6 +/-
      0.1). The preoperative Spitzer index was 4.4 +/- 1.4. Mean angina episodes per
      week were 12.6 +/- 9.3 and mean consumption of sublingual nitrates was 11.0 +/-
      9.4. At follow-up, overall mortality was 11% (n = 11), and cardiovascular death
      was 3%. A reduction in angina episodes per week >50% was observed in 88% of
      patients (from 12.6 +/- 9.3 to 2.7 +/- 1.13; p<0.0001). Mean consumption of
      sublingual nitrates decreased from 11.0 +/- 9.4 to 2.3 +/- 0.1 (p<0.0001). The
      Spitzer index significantly improved (from 4.4 +/- 0.1 to 2.3 +/- 0.1; p<0.0001).
      NYHA class and CCS class decreased from 2.6 +/- 0.1 to 2.0 +/- 0.1 and from 3.5
      +/- 0.1 to 1.7 +/- 0.1, respectively (both p<0.0001). CONCLUSIONS: SCS is an
      effective and safe therapeutic option for patients with chronic refractory angina
      and it is associated with improved functional status and QoL at follow-up.

PMID- 21892222
TI  - [Psycho-emotional impact of acute coronary syndromes].
AB  - BACKGROUND: Acute coronary syndromes can substantially disrupt the lives of our
      patients. However, patients' view of their illness is usually scarcely considered
      in routine medical practice. We aimed to investigate the psycho-emotional impact
      of acute coronary syndromes. METHODS: We studied 30 patients with acute coronary
      syndrome, aged <70 years. Before discharge, each patient was interviewed by a
      psychologist using a semi-structured interview; data were collected in the form
      of verbal reports. RESULTS: After learning that they had had a heart attack, 16
      patients (53%) reported a feeling of fear linked to the idea of death, sometimes
      real despair; 7 patients (23%) showed a weak emotional response, 4 (13%) reacted
      with denial, and 3 responded evasively. During the interview, 17 patients (57%)
      reported events relating to family life and 9 (30%) to work; all these events
      were negative and related to suffering, conflict, and stress. When compared to
      pre-admission status, 30% of patients experienced negative psychological changes,
      such as a sense of fragility, uncertainty and a redefinition of self-image, while
      50% reported no change. Surprisingly, 6 patients (20%) referred positive
      psychological changes. This positive restructuring was related to the patients'
      ability/need to change their lifestyle. This process entails a different vision
      of the past and the future, and is associated with a feeling of rebirth and
      physical wellbeing. CONCLUSIONS: The psycho-emotional effects of acute coronary
      syndromes may be immense, and may radically change the way the patient relates to
      himself and to the world. We often remain detached from these changes, and are
      sometimes even unaware of them.

PMID- 21892223
TI  - [Major epidemiological changes and clinical variables in patients undergoing a
      program of heart rehabilitation after cardiac surgery - MEPHISTOPHELES].
AB  - BACKGROUND: Recent observational studies show an increase of more complex and
      critically ill patients referred to Italian cardiac rehabilitation (CR)
      departments; the exact mechanisms underlying this phenomenon, however, have not
      been clearly identified. The aim of our study was to evaluate the epidemiological
      and clinical changes that occurred over the last decade in patients hospitalized
      in CR departments with high admittance rates. METHODS: We have retrospectively
      evaluated all patients admitted between 2002 and 2009 to our division of CR (n =
      3340, 1155 female, mean age 66.4 +/- 11 years) after recent cardiac surgery. The
      study population was divided into two homogeneous groups: the four-year period
      2002-2005, group A (n = 1614, 540 female, mean age 66.1 +/- 10 years) and the
      four-year period 2006-2009, group B (n = 1726, 615 female, mean age 67.4 +/- 11
      years). Data were compared using specific indicators of clinical complexity.
      RESULTS: Patients aged >75 years were more in group B compared to A (26.3 vs
      19.8%, p<0.0001), as well as patients with recent complex surgical interventions,
      such as combined coronary artery bypass grafting and heart valve surgery (16.4 vs
      10.2%, p<0.0001). An increased incidence of cardiovascular death (1.4 vs 0.6%,
      p=0.02), acute coronary syndrome (1.5 vs 0.7%, p=0.02) and persistent atrial
      fibrillation/flutter (13.5 vs 7.1%, p<0.0001) was observed in group B, as well as
      an increased prevalence of systolic heart failure (18.3 vs 9.0%, p<0.0001).
      Similarly, the incidence of acute respiratory failure episodes (1.0 vs 0.4%,
      p=0.05), the prevalence of patients admitted with a tracheostomy tube (2.6 vs
      0.2%, p<0.0001) and the incidence of acute renal failure (1.1 vs 0.5%, p=0.05)
      were significantly increased in group B. Postoperative infections and surgical
      wound complications were 4-fold higher in group B (13.9 vs 3.1%, p<0.0001, and
      12.8 vs 2.3%, p<0.0001, respectively). Compared to group A, patients of group B
      showed a significantly lower physical performance, as expressed by the Rivermead
      motility index (3.8 +/- 1.1 vs 5.2 +/- 0.8, p<0.001); moreover, the number of
      subjects able to perform an incremental training program was significantly lower
      in group B than group A (14.8 vs 60.6%, p<0.0001). Mean hospital stay was longer
      in group B than group A (25.4 +/- 13 vs 22.1 +/- 9 days, p<0.001). CONCLUSIONS:
      Our study, by collecting data from a CR division in northern Italy with high
      admittance rates, demonstrates a dramatic increase in clinical complexity over
      the last few years. This points to the need for new expertise and major resources
      to be allocated to CR departments.

PMID- 21892224
TI  - [Massive pulmonary embolism treated with selective infusion of tenecteplase].
AB  - Massive pulmonary embolism (PE) is a cardiovascular emergency due to a
      substantial obstruction of the pulmonary vascular bed, resulting in rapid right
      heart failure with a potentially fatal outcome.We present the case of a 50-year
      old woman with massive PE and recent trans-sphenoid surgery because of pituitary
      adenoma. An occluding embolus, arising from deep venous thrombosis of the lower
      limbs, was demonstrated in the right pulmonary artery with selective angiography
      and treated with selective loco-regional infusion of low-dose tenecteplase. To
      the best of our knowledge, this is the first case of selective administration of
      low-dose tenecteplase in the pulmonary artery with successful resolution of PE
      without the need for adjunctive interventional procedures.

PMID- 21892225
TI  - [How to expand the indications for an interventional procedure without comparing
      it with the best proven medical therapy: the case of carotid artery stenting in
      the CREST trial].

PMID- 21892226
TI  - Effect of Process Variables on the Microstructure of Hollow Hydroxyapatite
      Microspheres Prepared by a Glass Conversion Method.
AB  - Solid microspheres (diameter = 106-150 MUm) of a Li(2)O-CaO-B(2)O(3) glass were
      reacted in a K(2)HPO(4) solution to form hollow hydroxyapatite (HA) microspheres.
      The effect of the temperature (25 degrees -60 degrees C), K(2)HPO(4)
      concentration (0.01-0.25M), and pH (9-12) of the solution on the diameter (d) of
      the hollow core normalized to the diameter (D) of the HA microspheres, the
      surface area, and the pore size of the microsphere wall was studied. The
      statistically significant process variables that influenced these microstructural
      characteristics were evaluated using a factorial design approach. While the pH
      had little effect, the concentration of the solution had a marked effect on d/D,
      surface area, and pore size, whereas temperature markedly influenced d/D and pore
      size, but not the surface area. The largest hollow core size (d/D value ~ 0.6)
      was obtained at the lowest temperature (25 degrees C) or the lowest K(2)HPO(4)
      concentration (0.02M), while microspheres with the highest surface area (140
      m(2)/g), with pores of size 10-12 nm were obtained at the highest concentration
      (0.25M). The consequences of these results for potential application of these
      hollow HA microspheres as devices for local delivery of proteins, such as drugs
      or growth factors, are discussed.

PMID- 21892227
TI  - Enhanced Inter-helical Residue Contact Prediction in Transmembrane Proteins.
AB  - In this paper, based on a recent work by McAllister and Floudas who developed a
      mathematical optimization model to predict the contacts in transmembrane alpha
      helical proteins from a limited protein data set [1], we have enhanced this
      method by 1) building a more comprehensive data set for transmembrane alpha
      helical proteins and this enhanced data set is then used to construct the
      probability sets, MIN-1N and MIN-2N, for residue contact prediction, 2) enhancing
      the mathematical model via modifications of several important physical
      constraints and 3) applying a new blind contact prediction scheme on different
      protein sets proposed from analyzing the contact prediction on 65 proteins from
      Fuchs et al. [2]. The blind contact prediction scheme has been tested on two
      different membrane protein sets. Firstly it is applied to five carefully selected
      proteins from the training set. The contact prediction of these five proteins
      uses probability sets built by excluding the target protein from the training
      set, and an average accuracy of 56% was obtained. Secondly, it is applied to six
      independent membrane proteins with complicated topologies, and the prediction
      accuracies are 73% for 2ZY9A, 21% for 3KCUA, 46% for 2W1PA, 64% for 3CN5A, 77%
      for 3IXZA and 83% for 3K3FA. The average prediction accuracy for the six proteins
      is 60.7%. The proposed approach is also compared with a support vector machine
      method (TMhit [3]) and it is shown that it exhibits better prediction accuracy.

PMID- 21892228
TI  - Enhanced mechanical performance and biological evaluation of a PLGA coated beta
      TCP composite scaffold for load-bearing applications.
AB  - Porous beta-tricalcium phosphate (beta-TCP) has been used for bone repair and
      replacement in clinics due to its excellent biocompatibility, osteoconductivity,
      and biodegradability. However, the application of beta-TCP has been limited by
      its brittleness. Here, we demonstrated that an interconnected porous beta-TCP
      scaffold infiltrated with a thin layer of poly (lactic-co-glycolic acid) (PLGA)
      polymer showed improved mechanical performance compared to an uncoated beta-TCP
      scaffold while retaining its excellent interconnectivity and biocompatibility.
      The infiltration of PLGA significantly increased the compressive strength of beta
      TCP scaffolds from 2.90 MPa to 4.19 MPa, bending strength from 1.46 MPa to 2.41
      MPa, and toughness from 0.17 MPa to 1.44 MPa, while retaining an interconnected
      porous structure with a porosity of 80.65%. These remarkable improvements in the
      mechanical properties of PLGA-coated beta-TCP scaffolds are due to the
      combination of the systematic coating of struts, interpenetrating structural
      characteristics, and crack bridging. The in vitro biological evaluation
      demonstrated that rat bone marrow stromal cells (rBMSCs) adhered well,
      proliferated, and expressed alkaline phosphatase (ALP) activity on both the PLGA
      coated beta-TCP and the beta-TCP. These results suggest a new strategy for
      fabricating interconnected macroporous scaffolds with significantly enhanced
      mechanical strength for potential load-bearing bone tissue regeneration.

PMID- 21892229
TI  - "An Old Way to Solve an Old Problem": Provider Perspectives on Recovery-Oriented
      Services and Consumer Capabilities in New Mexico.
AB  - The goal of recovery has emerged as a core value in the reformation of public and
      private mental health services in the last twenty years. However, definitions of
      recovery remain as varied as methods of implementation. Through an ethnographic
      lens, we examine meanings of recovery in the context of a major statewide reform
      of mental health services in New Mexico, focusing specifically on provider-voiced
      concerns regarding recovery and recovery-oriented care. We argue that the concept
      of recovery functions as a symbol that seemingly reconciles the long-standing
      tension between biological and social explanations of mental illness. Drawing
      upon provider perspectives, we also discuss concerns that popular rhetoric about
      recovery may mask some needed fundamental changes to transform the mental health
      system to a recovery orientation. Finally, we consider recovery from a
      capabilities standpoint and discuss how this view lends itself to addressing both
      individual and social components of mental illness.

PMID- 21892230
TI  - Quantum Chemical Study of the Mechanism of Action of Vitamin K Carboxylase in
      Solvent.
AB  - We investigate the post-translational generation of Gla (gamma-carboxy glutamic
      acid) from Glu (glutamic acid) by vitamin K carboxylase (VKC) in solvent. VKC is
      thought to convert vitamin K, in the vitamin K cycle, to an alkoxide-epoxide
      form, which then reacts with CO(2) to generate an essential ingredient in blood
      coagulation, gamma-carboxyglutamic acid (Gla). The generation of Gla from Glu is
      found to be exergenic (-15 kcal/mol) in aqueous solution with the SM6 method. We
      also produced the free energy profile for this model biochemical process with
      other solvent methods (polarizable continuum model, dielectric polarizable
      continuum model) and different dielectric constants. The biological implications
      are discussed.

PMID- 21892231
TI  - Reported Contact with the Dead, Religious Involvement, and Death Anxiety in Late
      Life.
AB  - The purpose of this study is to examine the relationship between contact with the
      dead and death anxiety. The data come from an ongoing nationwide survey of older
      adults. A conceptual model is developed that contains the following theoretical
      linkages: (1) making contact with the dead instills a deeper appreciation of the
      connection that exists among all people; (2) this fundamental sense of
      connectedness with others fosters a deeper sense of religious meaning in life;
      and (3) individuals with a deeper sense of religious meaning in life are less
      likely to experience feelings of death anxiety than people who have not been able
      to find meaning in life through religion. The findings from this study provide
      support for each of these relationships. The theoretical implications of these
      hypotheses are discussed.

PMID- 21892232
TI  - AND/R: Advanced neutron diffractometer/reflectometer for investigation of thin
      films and multilayers for the life sciences.
AB  - An elastic neutron scattering instrument, the advanced neutron
      diffractometer/reflectometer (AND/R), has recently been commissioned at the
      National Institute of Standards and Technology Center for Neutron Research. The
      AND/R is the centerpiece of the Cold Neutrons for Biology and Technology
      partnership, which is dedicated to the structural characterization of thin films
      and multilayers of biological interest. The instrument is capable of measuring
      both specular and nonspecular reflectivity, as well as crystalline or
      semicrystalline diffraction at wave-vector transfers up to approximately 2.20 A(
      1). A detailed description of this flexible instrument and its performance
      characteristics in various operating modes are given.

PMID- 21892233
TI  - The Unintended Significance of Race: Environmental Racial Inequality in Detroit.
AB  - This article addresses shortcomings in the literature on environmental inequality
      by (a) setting forth and testing four models of environmental inequality and (b)
      explicitly linking environmental inequality research to spatial mismatch theory
      and to the debate on the declining significance of race. The explanatory models
      ask whether the distribution of blacks and whites around environmental hazards is
      the result of black/white income inequality, racist siting practices, or
      residential segregation. The models are tested using manufacturing facility and
      census data from the Detroit metropolitan area. It turns out that the
      distribution of blacks and whites around this region's polluting manufacturing
      facilities is largely the product of residential segregation which,
      paradoxically, has reduced black proximity to manufacturing facility pollution.

PMID- 21892234
TI  - Population Growth in High-Amenity Rural Areas: Does it Bring Socioeconomic
      Benefits for Long-Term Residents?
AB  - OBJECTIVE: A widely noted concern with amenity-driven rural population growth is
      its potential to yield only low-wage service-sector employment for long-term
      residents, while raising local costs of living. This research examines change in
      socioeconomic status during the 1990s for long-term residents of high-amenity,
      high-growth rural counties in the United States. METHODS: Using longitudinal data
      from the Panel Study of Income Dynamics, in combination with county-level
      information, we estimate growth-curve models to examine the extent to which the
      socioeconomic status of long-term residents is associated with amenity-related in
      migration. RESULTS: We find that, on average, residents in high-growth, amenity
      rich rural areas have higher income growth over time and higher levels of initial
      occupational prestige compared to those from other rural areas, but that
      socioeconomic gains are primarily for individuals with low baseline prestige.
      CONCLUSIONS: The socioeconomic gains made by long-term residents of high-growth,
      amenity-rich rural areas associated with net in-migration may be limited to
      individuals with low initial prestige and growth may be due to low-skill service
      sector jobs.

PMID- 21892235
TI  - Effect of a non-ionic surfactant, Merpol, on dye decolorization of Reactive blue
      19 by laccase.

PMID- 21892236
TI  - Anatomical Contributions to Hylobatid Taxonomy and Adaptation.
AB  - Compared with the great apes, the small-bodied hylobatids were treated
      historically as a relatively uniform group with 2 genera, Hylobates and the
      larger-bodied Symphalangus. Four genera are now recognized, each with a different
      chromosome number: Hoolock (hoolock) (38), Hylobates (44), Nomascus (crested
      gibbon) (52), and Symphalangus (siamang) (50). Previous morphological studies
      based on relative bone lengths, e.g., intermembral indices; molar tooth sizes;
      and body masses did not distinguish the 4 genera from each other. We applied
      quantitative anatomical methods to test the hypothesis that each genus can be
      differentiated from the others using the relative distribution of body mass to
      the forelimbs and hind limbs. Based on dissections of 13 hylobatids from captive
      facilities, our findings demonstrate that each of the 4 genera has a distinct
      pattern of body mass distribution. For example, the adult Hoolock has limb
      proportions of nearly equal mass, a pattern that differentiates it from species
      in the genus Hylobates, e.g., H. lar (lar gibbon), H. moloch (Javan gibbon), H.
      pileatus (pileated gibbon), Nomascus, and Symphalangus. Hylobates is distinct in
      having heavy hind limbs. Although Symphalangus has been treated as a scaled up
      version of Hylobates, its forelimb exceeds its hind limb mass, an unusual primate
      pattern otherwise found only in orangutans. This research provides new
      information on whole body anatomy and adds to the genetic, ecological, and
      behavioral evidence for clarifying the taxonomy of the hylobatids. The research
      also underscores the important contribution of studies on rare species in
      captivity.

PMID- 21892237
TI  - The Equivocal Relationship Between Territoriality and Scent Marking in Wild
      Saddleback Tamarins (Saguinus fuscicollis).
AB  - Researchers have often assumed that scent marking serves a territorial function
      in callitrichines, although some controversy exists. To fulfill such a function,
      scent marks should 1) prevent intrusions, 2) ensure access to feeding resources,
      3) enable avoidance of intergroup encounters, or 4) play an important role in the
      aggressive encounters between groups. We studied 13 saddleback tamarins (Saguinus
      fuscicollis) belonging to 3 free-ranging groups, which formed mixed-species
      troops with moustached tamarins (S. mystax) in the Amazonian rain forest of Peru.
      None of the predictions were confirmed. The tamarins used a border-marking
      strategy, marking more on the periphery of their territory. However, feeding
      trees in overlap and encounter areas received more scent marking but were still
      visited by neighboring groups. Intergroup encounters occurred more often than
      expected, and scent-marking frequency was not higher during them than when no
      other group was present. It appears that instead of defending a territory in the
      classic sense, the tamarins are optimizing signal transmission by depositing
      their scents where the probability of detection by neighbors is higher.
      Saddleback tamarins may use shared areas of their home ranges to exchange
      information with neighboring groups, perhaps regarding reproductive
      opportunities. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this
      article (doi:10.1007/s10764-011-9516-9) contains supplementary material, which is
      available to authorized users.

PMID- 21892238
TI  - Estrogen and Progestogen Correlates of the Structure of Female Copulation Calls
      in Semi-Free-Ranging Barbary Macaques (Macaca sylvanus).
AB  - Females of many Old World primates produce conspicuous vocalizations in
      combination with copulations. Indirect evidence exists that in Barbary macaques
      (Macaca sylvanus), the structure of these copulation calls is related to changes
      in reproductive hormone levels. However, the structure of these calls does not
      vary significantly around the timing of ovulation when estrogen and progestogen
      levels show marked changes. We here aimed to clarify this paradox by
      investigating how the steroid hormones estrogen and progesterone are related to
      changes in the acoustic structure of copulation calls. We collected data on semi
      free-ranging Barbary macaques in Gibraltar and at La Foret des Singes in
      Rocamadour, France. We determined estrogen and progestogen concentrations from
      fecal samples and combined them with a fine-grained structural analysis of female
      copulation calls (N = 775 calls of 11 females). Our analysis indicates a time lag
      of 3 d between changes in fecal hormone levels, adjusted for the excretion lag
      time, and in the acoustic structure of copulation calls. Specifically, we found
      that estrogen increased the duration and frequency of the calls, whereas
      progestogen had an antagonistic effect. Importantly, however, variation in
      acoustic variables did not track short-term changes such as the peak in estrogen
      occurring around the timing of ovulation. Taken together, our results help to
      explain why female Barbary macaque copulation calls are related to changes in
      hormone levels but fail to indicate the fertile phase.

PMID- 21892239
TI  - New and revisited species in Aspergillus section Nigri.
AB  - Four new species, Aspergillus eucalypticola, A. neoniger, A. fijiensis and A.
      indologenus are described and illustrated. Aspergillus eucalypticola was isolated
      from Eucalyptus leaf from Australia, and is related to A. tubingensis and A.
      costaricaensis, but could clearly be distinguished from them based on either beta
      tubulin or calmodulin sequence data. Aspergillus eucalypticola produced
      pyranonigrin A, funalenone, aurasperone B and other naphtho-gamma-pyrones.
      Aspergillus neoniger is also a biseriate species isolated from desert sand in
      Namibia, and mangrove water in Venezuela, which produces aurasperone B and
      pyranonigrin A. Aspergillus fijiensis is a uniseriate species related to A.
      aculeatinus, and was isolated from soil in Fiji, and from Lactuca sativa in
      Indonesia. This species is able to grow at 37  degrees C, and produces
      asperparalines and okaramins. Aspergillus indologenus was isolated from soil,
      India. This species also belongs to the uniseriate group of black aspergilli, and
      was found to be related to, but clearly distinguishable from A. uvarum based on
      beta-tubulin, calmodulin and ITS sequence data. Aspergillus indologenus produced
      the insecticidal compounds okaramins A, B, H, and two types of indol-alkaloids
      which have not been structure elucidated. Two other species, A. violaceofuscus
      and A. acidus, are revalidated based on molecular and extrolite data. Aspergillus
      violaceofuscus was found to be related to A. japonicus, and produced some of the
      same interesting indol-alkaloids as A. indologenus, and also produced several
      families of partially characterised extrolites that were also found in A.
      heteromorphus. Aspergillus acidus (previously known as A. foetidus var. pallidus
      and A. foetidus var. acidus) is also a valid species, while A. foetidus is a
      synonym of A. niger based on molecular and physiological data. Two other species
      described previously, A. coreanus and A. lacticoffeatus, were found to be colour
      mutants of A. acidus and A. niger, respectively. Methods which could be used to
      distinguish the two closely related and economically important species A. niger
      and A. awamori are also detailed. Although these species differ in their
      occurrence and several physiological means (elastase activities, abilities to
      utilise 2-deoxy-D-glucose as sole carbon source), our data indicate that only
      molecular approaches including sequence analysis of calmodulin or beta-tubulin
      genes, AFLP analysis, UP-PCR analysis or mtDNA RFLP analysis can be used reliably
      to distinguish these sibling species. Aspergillus section Nigri now includes 26
      taxa.

PMID- 21892240
TI  - Growth and hydrolase profiles can be used as characteristics to distinguish
      Aspergillus niger and other black aspergilli.
AB  - Wild type Aspergillus niger isolates from different biotopes from all over the
      world were compared to each other and to the type strains of other black
      Aspergillus species with respect to growth and extracellular enzyme profiles. The
      origin of the A. niger isolate did not result in differences in growth profile
      with respect to monomeric or polymeric carbon sources. Differences were observed
      in the growth rate of the A. niger isolates, but these were observed on all
      carbon sources and not specific for a particular carbon source. In contrast,
      carbon source specific differences were observed between the different species.
      Aspergillus brasiliensis is the only species able to grow on D-galactose, and A.
      aculeatus had significantly better growth on Locus Bean gum than the other
      species. Only small differences were found in the extracellular enzyme profile of
      the A. niger isolates during growth on wheat bran, while large differences were
      observed in the profiles of the different black aspergilli. In addition,
      differences were observed in temperature profiles between the black Aspergillus
      species, but not between the A. niger isolates, demonstrating no isolate-specific
      adaptations to the environment.These data indicate that the local environment
      does not result in stable adaptations of A. niger with respect to growth profile
      or enzyme production, but that the potential is maintained irrespective of the
      environmental parameters. It also demonstrates that growth, extracellular protein
      and temperature profiles can be used for species identification within the group
      of black aspergilli.

PMID- 21892241
TI  - Analysis of regulation of pentose utilisation in Aspergillus niger reveals
      evolutionary adaptations in Eurotiales.
AB  - Aspergilli are commonly found in soil and on decaying plant material. D-xylose
      and L-arabinose are highly abundant components of plant biomass. They are
      released from polysaccharides by fungi using a set of extracellular enzymes and
      subsequently converted intracellularly through the pentose catabolic pathway
      (PCP).In this study, the L-arabinose responsive transcriptional activator (AraR)
      is identified in Aspergillus niger and was shown to control the L-arabinose
      catabolic pathway as well as expression of genes encoding extracellular L
      arabinose releasing enzymes. AraR interacts with the D-xylose-responsive
      transcriptional activator XlnR in the regulation of the pentose catabolic
      pathway, but not with respect to release of L-arabinose and D-xylose.AraR was
      only identified in the Eurotiales, more specifically in the family Trichocomaceae
      and appears to have originated from a gene duplication event (from XlnR) after
      this order or family split from the other filamentous ascomycetes. XlnR is
      present in all filamentous ascomycetes with the exception of members of the
      Onygenales. Since the Onygenales and Eurotiales are both part of the subclass
      Eurotiomycetidae, this indicates that strong adaptation of the regulation of
      pentose utilisation has occurred at this evolutionary node. In Eurotiales a
      unique two-component regulatory system for pentose release and metabolism has
      evolved, while the regulatory system was lost in the Onygenales. The observed
      evolutionary changes (in Eurotiomycetidae) mainly affect the regulatory system as
      in contrast, homologues for most genes of the L-arabinose/D-xylose catabolic
      pathway are present in all the filamentous fungi, irrespective of the presence of
      XlnR and/or AraR.

PMID- 21892242
TI  - New species in Aspergillus section Terrei.
AB  - Section Terrei of Aspergillus was studied using a polyphasic approach including
      sequence analysis of parts of the beta-tubulin and calmodulin genes and the ITS
      region, macro- and micromorphological analyses and examination of extrolite
      profiles to describe three new species in this section. Based on phylogenetic
      analysis of calmodulin and beta-tubulin sequences seven lineages were observed
      among isolates that have previously been treated as A. terreus and its subspecies
      by Raper & Fennell (1965) and others. Aspergillus alabamensis, A. terreus var.
      floccosus, A. terreus var. africanus, A. terreus var. aureus, A. hortai and A.
      terreus NRRL 4017 all represent distinct lineages from the A. terreus clade.
      Among them, A. terreus var. floccosus, A. terreus NRRL 4017 and A. terreus var.
      aureus could also be distinguished from A. terreus by using ITS sequence data.
      New names are proposed for A. terreus var. floccosus, A. terreus var. africanus,
      A. terreus var. aureus, while Aspergillus hortai is recognised at species level.
      Aspergillus terreus NRRL 4017 is described as the new species A. pseudoterreus.
      Also included in section Terrei are some species formerly placed in sections
      Flavipedes and Versicolores. A. clade including the type isolate of A. niveus
      (CBS 115.27) constitutes a lineage closely related to A. carneus. Fennellia
      nivea, the hypothesized teleomorph is not related to this clade. Aspergillus
      allahabadii, A. niveus var. indicus, and two species originally placed in section
      Versicolores, A. ambiguus and A. microcysticus, also form well-defined lineages
      on all trees. Species in Aspergillus section Terrei are producers of a diverse
      array of secondary metabolites. However, many of the species in the section
      produce different combinations of the following metabolites: acetylaranotin,
      asperphenamate, aspochalamins, aspulvinones, asteltoxin, asterric acid,
      asterriquinones, aszonalenins, atrovenetins, butyrolactones, citreoisocoumarins,
      citreoviridins, citrinins, decaturins, fulvic acid, geodins, gregatins,
      mevinolins, serantrypinone, terreic acid (only the precursor 3,6
      dihydroxytoluquinone found), terreins, terrequinones, terretonins and territrems.
      The cholesterol-lowering agent mevinolin was found in A. terreus and A.
      neoafricanus only. The hepatotoxic extrolite citrinin was found in eight species:
      A. alabamensis, A. allahabadii, A. carneus, A. floccosus, A. hortai, A.
      neoindicus, A. niveus and A. pseudoterreus. The neurotoxic extrolite
      citreoviridin was found in five species: A. neoafricanus, A. aureoterreus, A.
      pseudoterreus, A. terreus and A. neoniveus. Territrems, tremorgenic extrolites,
      were found in some strains of A. alabamensis and A. terreus.

PMID- 21892243
TI  - Two new aflatoxin producing species, and an overview of Aspergillus section
      Flavi.
AB  - Aspergillus subgenus Circumdati section Flavi includes species with usually
      biseriate conidial heads, in shades of yellow-green to brown, and dark sclerotia.
      Several species assigned to this section are either important mycotoxin producers
      including aflatoxins, cyclopiazonic acid, ochratoxins and kojic acid, or are used
      in oriental food fermentation processes and as hosts for heterologous gene
      expression. A polyphasic approach was applied using morphological characters,
      extrolite data and partial calmodulin, beta-tubulin and ITS sequences to examine
      the evolutionary relationships within this section. The data indicate that
      Aspergillus section Flavi involves 22 species, which can be grouped into seven
      clades. Two new species, A. pseudocaelatus sp. nov. and A. pseudonomius sp. nov.
      have been discovered, and can be distinguished from other species in this section
      based on sequence data and extrolite profiles. Aspergillus pseudocaelatus is
      represented by a single isolate collected from Arachis burkartii leaf in
      Argentina, is closely related to the non-aflatoxin producing A. caelatus, and
      produces aflatoxins B & G, cyclopiazonic acid and kojic acid, while A.
      pseudonomius was isolated from insects and soil in the USA. This species is
      related to A. nomius, and produces aflatoxin B(1) (but not G-type aflatoxins),
      chrysogine and kojic acid. In order to prove the aflatoxin producing abilities of
      the isolates, phylogenetic analysis of three genes taking part in aflatoxin
      biosynthesis, including the transcriptional regulator aflR, norsolonic acid
      reductase and O-methyltransferase were also carried out. A detailed overview of
      the species accepted in Aspergillus section Flavi is presented.

PMID- 21892244
TI  - New taxa in Aspergillus section Usti.
AB  - Based on phylogenetic analysis of sequence data, Aspergillus section Usti
      includes 21 species, inclucing two teleomorphic species Aspergillus
      heterothallicus (= Emericella heterothallica) and Fennellia monodii. Aspergillus
      germanicus sp. nov. was isolated from indoor air in Germany. This species has
      identical ITS sequences with A. insuetusCBS 119.27, but is clearly distinct from
      that species based on beta-tubulin and calmodulin sequence data. This species is
      unable to grow at 37  degrees C, similarly to A. keveii and A. insuetus.
      Aspergillus carlsbadensis sp. nov. was isolated from the Carlsbad Caverns
      National Park in New Mexico. This taxon is related to, but distinct from a clade
      including A. calidoustus, A. pseudodeflectus, A. insuetus and A. keveii on all
      trees. This species is also unable to grow at 37  degrees C, and acid production
      was not observed on CREA. Aspergillus californicus sp. nov. is proposed for an
      isolate from chamise chaparral (Adenostoma fasciculatum) in California. It is
      related to a clade including A. subsessilis and A. kassunensis on all trees. This
      species grew well at 37  degrees C, and acid production was not observed on CREA.
      The strain CBS 504.65 from soil in Turkey showed to be clearly distinct from the
      A. deflectus ex-type strain, indicating that this isolate represents a distinct
      species in this section. We propose the name A. turkensis sp. nov. for this
      taxon. This species grew, although rather restrictedly at 37  degrees C, and acid
      production was not observed on CREA. Isolates from stored maize, South Africa, as
      a culture contaminant of Bipolaris sorokiniana from indoor air in Finland proved
      to be related to, but different from A. ustus and A. puniceus. The taxon is
      proposed as the new species A. pseudoustus. Although supported only by low
      bootstrap values, F. monodii was found to belong to section Usti based on
      phylogenetic analysis of either loci BLAST searches to the GenBank database also
      resulted in closest hits from section Usti. This species obviously does not
      belong to the Fennellia genus, instead it is a member of the Emericella genus.
      However, in accordance with the guidelines of the Amsterdam Declaration on fungal
      nomenclature (Hawksworth et al. 2011), and based on phylogenetic and
      physiological evidence, we propose the new combination Aspergillus monodii comb.
      nov. for this taxon. Species assigned to section Usti can be assigned to three
      chemical groups based on the extrolites. Aspergillus ustus, A. granulosus and A.
      puniceus produced ustic acid, while A. ustus and A. puniceus also produced
      austocystins and versicolorins. In the second chemical group, A. pseudodeflectus
      produced drimans in common with the other species in this group, and also several
      unique unknown compounds. Aspergillus calidoustus isolates produced drimans and
      ophiobolins in common with A. insuetus and A. keveii, but also produced austins.
      Aspergillus insuetus isolates also produced pergillin while A. keveii isolates
      produced nidulol. In the third chemical group, E. heterothallica has been
      reported to produce emethallicins, 5'-hydroxyaveranthin, emeheterone,
      emesterones, 5'-hydroxyaveranthin.

PMID- 21892245
TI  - Contributions of Maternal Adult Attachment to Socialization of Coping.
AB  - This research examined whether maternal adult attachment predicted the coping
      suggestions mothers made to their children. A sample of 157 youth (M age = 12.42,
      SD = 1.20) and their maternal caregivers completed semi-structured interviews and
      questionnaires in a two-wave longitudinal study. Results revealed that maternal
      insecure attachment predicted fewer engagement coping suggestions (orienting
      toward stress) and heightened disengagement coping suggestions (avoiding or
      denying stress) both concurrently and over time. These associations were found
      after adjusting for other relevant characteristics of the child, mother, and
      family context. This study contributes to our understanding of the implications
      of adult attachment for parenting behavior, suggesting that insecure attachment
      undermines a parent's ability to provide adaptive coping guidance to their
      children.

PMID- 21892246
TI  - Preparation and optical properties of novel bioactive photonic crystals obtained
      from core-shell poly(styrene/alpha-tert-butoxy-omega-vinylbenzyl-polyglycidol)
      microspheres.
AB  - Optical properties of polymer microspheres with polystyrene cores and
      polyglycidol-enriched shells poly(styrene/alpha-tert-butoxy-omega-vinylbenzyl
      polyglycidol) (P(S/PGL) particles with number average diameters D(n) determined
      by scanning electron microscopy equal 237 and 271 nm), were studied before and
      after immobilization of ovalbumin. The particles were synthesized by emulsifier
      free emulsion copolymerization of styrene and polyglycidol macromonomer
      (poly(styrene/alpha-tert-butoxy-omega-vinylbenzyl-polyglycidol)) initiated with
      potassium persulfate. Molar fraction of polyglycidol units in the interfacial
      layer of the microspheres determined by XPS was equal 42.6 and 34.0%, for the
      particles with D(n) equal 137 and 271 nm, respectively. Colloidal crystals from
      the aforementioned particles were prepared by deposition of particle suspensions
      on the glass slides and subsequent evaporation of water. It was found that
      optical properties of colloidal crystals from the P(S/PGL) microspheres strongly
      depend on modification of their interfacial layer by covalent immobilization of
      ovalbumin. The coating of particles with ovalbumin resulted in decreasing their
      refractive index from 1.58 to 1.52.

PMID- 21892247
TI  - Effect of hydrophobic and hydrophilic additives on sol-gel transition and release
      behavior of timolol maleate from polycaprolactone-based hydrogel.
AB  - The objective of this work was to delineate the effect of hydrophilic and
      hydrophobic polymeric additives on sol-gel transition and release profile of
      timolol maleate (TM) from poly (ethylene glycol)-poly (epsilon-caprolactone)-
      poly (ethylene glycol) (PEG-PCL-PEG)-based thermosensitive hydrogel.
      Polycaprolactone (hydrophobic additive) and polyvinyl alcohol (PVA) (hydrophilic
      additive) reduced critical gel concentration of PEG-PCL-PEG triblock polymer. The
      effect of PCL on sol-gel transition was more pronounced than PVA. However, with
      PCL no statistically significant difference in release profile was observed. The
      effect of PVA on release profile was more pronounced, which reduced the
      cumulative percentage release of TM from 86.4+/-0.8% to 73.7+/-1.8% over 316 h.
      Moreover, cytotoxicity of the hydrogel was also investigated utilizing rabbit
      primary corneal epithelial culture cells. No significant cytotoxicity of hydrogel
      alone or in presence of additives was observed. So, polymeric additive strategy
      serves as a valuable tool for optimizing TM release kinetics from PEG-PCL-PEG
      hydrogel matrix.

PMID- 21892248
TI  - Threat of allergenic airborne grass pollen in Szczecin, NW Poland: the dynamics
      of pollen seasons, effect of meteorological variables and air pollution.
AB  - The dynamics of Poaceae pollen season, in particularly that of the Secale genus,
      in Szczecin (western Poland) 2004-2008 was analysed to establish a relationship
      between the meteorological variables, air pollution and the pollen count of the
      taxa studied. Consecutive phases during the pollen season were defined for each
      taxon (1, 2.5, 5, 25, 50, 75, 95, 97.5, 99% of annual total), and duration of the
      season was determined using the 98% method. On the basis of this analysis, the
      temporary differences in the dynamics of the seasons were most evident for Secale
      in 2005 and 2006 with the longest main pollen season (90% total pollen). The
      pollen season of Poaceae started the earliest in 2007, when thermal conditions
      were the most favourable. Correlation analysis with meteorological factors
      demonstrated that the relative humidity, mean and maximum air temperature, and
      rainfall were the factors influencing the average daily pollen concentrations in
      the atmosphere; also, the presence of air pollutants such as ozone, PM(10) and
      SO(2) was statistically related to the pollen count in the air. However, multiple
      regression models explained little part of the total variance. Atmospheric
      pollution induces aggravation of symptoms of grass pollen allergy.

PMID- 21892249
TI  - The pollen season dynamics and the relationship among some season parameters
      (start, end, annual total, season phases) in Krakow, Poland, 1991-2008.
AB  - The dynamics of 15 taxa pollen seasons in Krakow, in 1991-2008 was monitored
      using a Burkard volumetric spore trap of the Hirst design. The highest daily
      pollen concentrations were achieved in the first half of May, and they were
      caused mainly by Betula and Pinus pollen. The second period of the high
      concentrations took place from the middle of July to the end of August (mainly
      Urtica pollen). Tree pollen seasons were shorter (18-24 days) in comparison with
      the most herbaceous pollen seasons (73-89 days), except at Artemisia and Ambrosia
      seasons (30 and 24 days, respectively). The season phases (percentyles) of the
      spring and late-summer taxa were the most variable in the consecutive years. The
      highest annual sums were noted for Urtica, Poaceae (herbaceous pollen seasons)
      and for Betula, Pinus, Alnus (tree pollen seasons), and the highest variability
      of annual totals was stated for Urtica, Populus, Fraxinus and the lowest for
      Ambrosia, Corylus, Poaceae. For the plants that pollinate in the middle of the
      pollen season (Quercus, Pinus and Rumex), the date of the season start seems not
      to be related to the season end, while for late pollen seasons, especially for
      Ambrosia and Artemisia, the statistically negative correlation between the start
      and the end season dates was found. Additionally, for the most studied taxa, the
      increase in annual pollen totals was observed. The presented results could be
      useful for the allergological practice and general botanical knowledge.

PMID- 21892250
TI  - Involuntary movements and their correlates in first-episode psychoses.

PMID- 21892251
TI  - Individual and ethnic aspects of preoperative planning for posttraumatic
      rhinoplasty.
AB  - The aim of this study was to compare the aesthetic results of post traumatic
      rhinoplasty among Europeans with populations of healthy Caucasians described in
      earlier reports, and to collate correct parameters of nasal shape in healthy
      representatives of both sexes and various races for improvement in aesthetic
      results of surgery. 3-D scanning of the face was performed in 54 patients after
      posttraumatic septorhinoplasty. Analysis of 3D model was based on two indices of
      the nasal proportions and four angles of the region from 18 anthropological
      points. Parameters of the nasal shape in addition to gender were compared to
      average values of healthy Caucasian population, described before. Normal
      characteristics of the nose among individuals of three races from previous
      studies were also compared to one another. In females, mean height and width of
      the nose as well as length of both nostrils was smaller. Neither were there any
      significant differences in width of the nostrils and length of the nasal pyramid
      nor nasal prominence. Nasal proportions were similar in both sexes. Some of the
      nasal angles differed in addition to gender. Posttraumatic rhinoplasty resulted
      in correct shape of the nose similar to the healthy Caucasian population. The
      aesthetic nose differ among healthy individuals of the three races analysed.
      While preoperative planning is important, knowledge of the normal values of
      parameters characterising shape in both genders is equally important as the
      individual differences in relation to the whole face.

PMID- 21892252
TI  - A study of cleft lip/palate in a community in the South East of Ghana.
AB  - The previous study in Wudoaba villages suggested that cleft lip and cleft palate
      (CL/CP) may be endemic in the Wudoaba cluster of villages in the Ketu South
      District of the Volta Region in South East Ghana. The study was to detect the
      prevalence of CL/CP in the Wudoaba communities and to investigate the factors
      associated with the causes of this malformation in the area. Two different
      interview-based questionnaires were designed to collect data over a period of 3
      days from March 27 to 29, 2006. A purposive and accidental random sampling
      technique was used in the administering of the various questionnaires to the
      respondents. Data collected were recorded and analyzed with SPSS version 17.0. A
      total 99 respondents, with a mean age of 55.0 years, were interviewed. Out of it,
      57.6% (n = 57) were related to their spouses: 54 first cousins and three other
      family relations. The prevalence of CL/CP is at least 6.3 per 1,000 people (i.e.,
      25/4,000). Majority (56.0%, n = 14) of the cleft cases were unilateral.
      Interviews revealed that genetic homogeneity and vitamin deficiencies in this
      community may be a causal factor for the high prevalence of CL/CP. This community
      provides clues suggesting that the magnitude of CL/CP may be larger than other
      studies and identifies the Wudoaba population as one that could be further
      studied to explore the underlying factors causing this congenital malformation.

PMID- 21892253
TI  - Oxalic acid, versatile peroxidase secretion and chelating ability of Bjerkandera
      fumosa in rich and limited culture conditions.
AB  - Efficient ligninolytic systems of wood-degrading fungi include not only oxidizing
      enzymes, but also low-molecular-weight effectors. The ability of Bjerkandera
      fumosa to secrete oxalic acid and versatile peroxidase (VP) in nitrogen-rich and
      nitrogen-limited media was studied. Higher activity of VP was determined in the
      nitrogen-limited media but greater concentration of oxalic acid was observed in
      the cultures of B. fumosa without nitrogen limitation. Ferric ions chelating
      ability of Bjerkandera fumosa studied in ferric ions limited media was correlated
      with the increased level of oxalic acid. The presence of hydroxamate-type
      siderophores in B. fumosa media were also detected. Oxalate decarboxylase was
      found to be responsible for regulation of oxalic acid concentration in the tested
      B. fumosa cultures.

PMID- 21892254
TI  - Ultrafiltrative separation of rhamnolipid from culture medium.
AB  - Classic methods of biosurfactant separation are difficult and require large
      amounts of organic solvents, thus generate high amounts of waste. This work
      presents and discusses in detail an original procedure to separate rhamnolipid
      from fermentation broth using high performance membrane techniques. Due to the
      unique properties of surface active agents, such as capability of forming
      aggregates above the critical micelle concentration, it is possible to easily
      purify the biosurfactant with high efficacy using inexpensive and commonly used
      membranes. In this article, two-stage ultrafiltration is proposed as a method for
      separating and purifying rhamnolipid from the culture medium. The obtained
      purified rhamnolipid solution was capable of reducing surface tension of water
      down to 28.6 mN/m at critical micelle concentration of 40 mg/l. Separation of
      rhamnolipid was confirmed by HPLC; three types of rhamnolipids were identified
      (RL1, RL2, RL4), with considerable predominance of RL2.

PMID- 21892255
TI  - Near-IR imaging of Erbium Laser Ablation with a Water Spray.
AB  - Near-IR (NIR) imaging can be used to view the formation of ablation craters
      during laser ablation since the enamel of the tooth is almost completely
      transparent near 1310-nm(1). Laser ablation craters can be monitored under
      varying irradiation conditions to assess peripheral thermal and transient-stress
      induced damage, measure the rate and efficiency of ablation and provide insight
      into the ablation mechanism. There are fundamental differences in the mechanism
      of enamel ablation using erbium lasers versus carbon dioxide laser systems due to
      the nature of the primary absorber and it is necessary to have water present on
      the tooth surface for efficient ablation at erbium laser wavelengths. In this
      study, sound human tooth sections of approximately 2-3-mm thickness were
      irradiated by free running and Q-switched Er:YAG & Er:YSGG lasers under varying
      conditions with and without a water spray. The incision area in the interior of
      each sample was imaged using a tungsten-halogen lamp with a band-pass filter
      centered at 1310-nm combined with an InGaAs area camera with a NIR zoom
      microscope. Obvious differences in the crater evolution were observed between
      CO(2) and erbium lasers. Ablation stalled after a few laser pulses without a
      water spray as anticipated. Efficient ablation was re-initiated by resuming the
      water spray. Micro-fractures were continuously produced apparently driven along
      prism lines during multi-pulse ablation. These fractures or fissures appeared to
      merge together as the crater evolved to form the leading edge of the ablation
      crater. These observations support the proposed thermo-mechanical mechanisms of
      erbium laser involving the strong mechanical forces generated by selective
      absorption by water.

PMID- 21892256
TI  - Dentin bond strength after ablation using a CO(2) laser operating at high pulse
      repetition rates.
AB  - Pulsed CO(2) lasers show great promise for the rapid and efficient ablation of
      dental hard tissues. Our objective was to demonstrate that CO(2) lasers operated
      at high repetition rates can be used for the rapid removal of dentin without
      excessive thermal damage and without compromising adhesion to restorative
      materials. Human dentin samples (3*3mm(2)) were rapidly ablated with a pulsed
      CO(2) laser operating at a wavelength of 9.3-MUm, pulse repetition rate of 300-Hz
      and an irradiation intensity of 18-J/cm(2). The bond strength to composite was
      determined by the modified single plane shear test. There were 8 test groups each
      containing 10 blocks: negative control (non-irradiated non-etched), positive
      control (non-irradiated acid-etched), and six laser treated groups (three etched
      and three non-etched sets). The first and second etched and non-etched sets were
      ablated at a speed of 25 mm/sec and 50 mm/sec with water, respectively. The third
      set was also ablated at 50 mm/sec without application of water during laser
      irradiation. Minimal thermal damage was observed on the dentin surfaces for which
      water cooling was applied. Bond strengths exceeded 20 MPa for laser treated
      surfaces that were acid-etched after ablation (25-mm/sec: 29.9-MPa, 50-mm/sec:
      21.3-MPa). The water-cooled etched laser groups all produced significantly
      stronger bonds than the negative control (p<0.001) and a lower bond strength than
      the positive control (p<0.05). These measurements demonstrate that dentin
      surfaces can be rapidly ablated by a CO(2) lasers with minimal peripheral thermal
      damage. Additional studies are needed to determine if a lower bond strength than
      the acid-etched control samples is clinically significant where durability of
      these bonded restoration supersedes high bond strength.

PMID- 21892257
TI  - Imaging Simulated Secondary Caries Lesions with Cross Polarization OCT.
AB  - The clinical diagnosis of secondary caries has been found to account for the
      replacement of the majority of intra-coronal restorations. Current methods to
      diagnose the presence of these lesions at early stages are considered
      insufficient due to their low sensitivity. Polarization-sensitive optical
      coherence tomography (PS-OCT) imaging studies have confirmed its effectiveness
      for imaging carious subsurface lesions in enamel and dentin. The objective of
      this study was to determine if PS-OCT can be used to nondestructively image
      demineralization through resin restorations on extracted teeth with both
      simulated and natural lesions. Simulated secondary caries lesions were created by
      exposing cavity preparations made in extracted human teeth to a demineralizing
      solution for 48 hours and subsequently restoring with resin. Negative control
      restorations were also prepared on each tooth. Optical changes in demineralized
      versus control preparations beneath restorations were measured as a function of
      depth using PS-OCT. PS-OCT images indicated that a significant increase in
      reflectivity and depth occurred in the simulated lesions compared with the
      control preparations. This study suggests that PS-OCT is well-suited to
      nondestructively detect early caries lesions in enamel beneath composite
      restorations.

PMID- 21892258
TI  - Endotracheal intubation skill acquisition by medical students.
AB  - BACKGROUND: During the course of their training, medical students may receive
      introductory experience with advanced resuscitation skills. Endotracheal
      intubation (ETI--the insertion of a breathing tube into the trachea) is an
      example of an important advanced resuscitation intervention. Only limited data
      characterize clinical ETI skill acquisition by medical students. We sought to
      characterize medical student acquisition of ETI procedural skill. METHODS: The
      study included third-year medical students participating in a required
      anesthesiology clerkship. Students performed ETI on operating room patients under
      the supervision of attending anesthesiologists. Students reported clinical
      details of each ETI effort, including patient age, sex, Mallampati score, number
      of direct laryngoscopies and ETI success. Using mixed-effects regression, we
      characterized the adjusted association between ETI success and cumulative ETI
      experience. RESULTS: ETI was attempted by 178 students on 1,646 patients (range 1
      23 patients per student; median 9 patients per student, IQR 6-12). Overall ETI
      success was 75.0% (95% CI 72.9-77.1%). Adjusted for patient age, sex, Mallampati
      score and number of laryngoscopies, the odds of ETI success improved with
      cumulative ETI encounters (odds ratio 1.09 per additional ETI encounter; 95% CI
      1.04-1.14). Students required at least 17 ETI encounters to achieve 90% predicted
      ETI success. CONCLUSIONS: In this series medical student ETI proficiency was
      associated with cumulative clinical procedural experience. Clinical experience
      may provide a viable strategy for fostering medical student procedural skills.

PMID- 21892259
TI  - Automatic Alignment of Myocardial Perfusion Images with Contrast Cardiac
      Tomography.
AB  - Explicit fusion of perfusion data from Positron Emission Tomography (PET) or
      Single Photon Emission Computed Tomography (SPECT) with coronary artery anatomy
      from Computed Tomographic Coronary Angiography (CTCA) has been shown to improve
      the diagnostic yield for coronary artery disease (CAD) compared to either
      modality alone. However, most clinically available methods were developed for
      multimodal scanners or require interactive alignment prior to display and
      analysis. A new approach was developed to register and display the two
      distributions obtained either from a single multimodal imager or from separate
      scanners, and a preliminary validation was undertaken using interactive alignment
      by experts.

PMID- 21892260
TI  - Palestinian children in the hemato-oncology ward of an israeli hospital.
AB  - PURPOSE: An encounter between Palestinian parents of children with cancer and
      Israeli medical staff is a very special situation where "potential enemies"
      interact in a caring, trusting and intimate relationship for long periods of
      time. Our aim was to study the psychological and cultural encounter in order to
      understand the dynamics involved. METHOD: The study is a qualitative one. Data
      was collected by way of structured in-depth interviews. Participants were
      physicians and nurses employed in the department, and Palestinian parents
      accompanying their children who were hospitalized during the research period.
      RESULTS: SIX MAIN THEMES EMERGED FROM THE ANALYSIS OF THE INTERVIEWS: (1) The
      decision to come to Israel for treatment. (2) The "meeting points" of the two
      peoples: the Israeli check points and the Palestinian Authority permits. (3)
      Encounter with the Israeli hospital. (4) Relationship between medical staff and
      parents. (5) Language and cultural barriers. (6) Emotions, thoughts and behaviors
      during high security tension. CONCLUSION: The interviews depict a poignant
      picture of the unique encounter between Israeli Doctors and nurses and
      Palestinian parents. The psychological mechanism used by parents and doctors is
      "splitting"-having a dichotomized, simple emotional-perceptual picture of a
      situation with no conflicts. Nurses use another psychological mechanism in
      addition which enables them to contain the paradox and the conflict.

PMID- 21892262
TI  - Late Relapse and Follow-up Protocols in Testicular Germ Cell Tumours: The
      Edinburgh Cancer Centre Experience and Review of the Literature.
AB  - AIMS: To identify clinicopathological features and outcomes in patients with late
      relapse (LR) of testicular germ cell tumours (GCTs) in order to guide follow-up
      policy. MATERIALS AND METHODS: The Edinburgh Cancer Centre (ECC) database
      identified all patients diagnosed with testicular GCT between 1988 and 2002. Of
      703 patients, six relapsed more than 24 months after their initial treatment. A
      retrospective casenote review was performed to extract clinical, pathological,
      treatment and outcome data. RESULTS: Six patients (0.85%) underwent late relapse.
      All patients presented initially with stage I disease and five were classified as
      good risk (International Germ Cell Consensus Classification, IGCCC). Median time
      to LR was 31 months. Two patients had previously relapsed less than 24 months
      from initial diagnosis. Markers at the time of relapse were normal in all
      patients. In all cases of late relapse disease was confined to axial
      lymphadenopathy. Three patients were treated with chemotherapy alone, two
      patients underwent surgical resection and one patient received combined
      treatment. All patients obtained a complete response and all remain disease free
      with a median follow-up of 52 months. CONCLUSIONS: The incidence of late relapse
      in this series is low. Chemo-naive patients with LR were successfully salvaged
      with chemotherapy alone and patients previously exposed to cisplatin-based
      chemotherapy were salvaged with complete surgical excision. The optimal length of
      follow-up in patients with testicular germ cell tumours is not known and practice
      varies widely. In this cohort of 703 patients, only one patient who relapsed was
      picked up by additional clinic follow-up between 5 and 10 years. Thus, on the
      basis of this small series, the authors suggest that follow-up after five years
      may not be justified.

PMID- 21892261
TI  - Biological Markers Predictive of Invasive Recurrence in DCIS.
AB  - DCIS is a heterogeneous group of non-invasive cancers of the breast characterized
      by various degrees of differentiation and unpredictable propensity for
      transformation into invasive carcinoma. We examined the expression and prognostic
      value of 9 biological markers with a potential role in tumor progression in 133
      patients with pure DCIS treated with breast conserving surgery alone, between
      1982-2000. Histology was reviewed and immunohistochemical staining was performed.
      Pearson correlation coefficient was used to determine the associations between
      markers and histopathological features. Univariate and multivariate analysis
      examined associations between time to recurrence and clinicopathologic features
      and biological markers.Median age at diagnosis was 55 years (25-85). With a
      median follow up of 8.91 years, 41/133 patients recurred (21 as invasive
      recurrence). In this cohort 13.5% had low, 43% intermediate and 42% high nuclear
      grade. Comedo necrosis was found in 65% of cases. Expression of ER (62.4%), PR
      (55.6%), HER2/neu (31.6%), MIB1 (39.8%), p53 (22.6%), p21 (39.8%), Cyclin D1
      (95.5%) calgranulin (20.5%), psoriasin (12%), was found in DCIS. HER2/neu was
      overexpressed in 45% that recurred as DCIS and 42.9% that recurred as invasive
      cancer, and only in 26.1% in cases that never recurred. On univariate analysis,
      HER2/neu overexpression was the only marker associated with an increased risk for
      any recurrence (p = 0.044). The hazard ratio for recurrence for HER2/neu positive
      DCIS was 1.927 (confidence interval 1.016-3.653) compared to HER2 negative DCIS.
      On multivariate analysis, HER2/neu overexpression remained the only independent
      variable significantly associated with any recurrence (p = 0.014) and with
      invasive recurrence (p = 0.044).This data suggest that HER2/neu testing may
      become an important parameter in the management of DCIS and the treatment of
      cases with positive HER2/neu status could be modified accordingly, similar to the
      current approach for HER2/neu positive invasive disease.

PMID- 21892263
TI  - Expression levels of thymidylate synthase, thymidylate phosphorylase and
      dihydropyrimidine dehydrogenase in head and neck squamous cell carcinoma:
      preliminary study.
AB  - INTRODUCTION: Pharyngo-laryngeal tumors classified as T3-4, N0-3, M0, are
      conventionally treated by mutilating surgery (total (pharyngo)-laryngectomy). Neo
      adjuvant chemotherapy with 5-FU/platinum salt can be proposed in an attempt to
      preserve the larynx. The level of the response to chemotherapy ranges from 36 to
      54% of cases. Thus, a large number of patients receive chemotherapy that is
      ineffective and not free from adverse effects. Three main enzymes are involved in
      the metabolism of 5-FU: thymidylate synthase (TS), thymidylate phosphorylase (TP)
      and dihydropyrimidine dehydrogenase (DPD). Several studies suggest that a high
      level of expression of these three genes correlates with a poor clinical response
      to 5-FU. The main purpose of our study was to look for a correlation between the
      levels of expression of the genes for sensitivity to 5-FU (TS, TP, DPD) within
      the tumor and the clinical response observed after three courses of chemotherapy
      combining 5-FU/platinum salt in patients presenting with advanced cancer of the
      pharyngo-larynx. METHODS: This was a prospective genetic study that had required
      approval from the Ethics Committee. The main assessment criterion was based on
      the assessment of the clinical response by an ENT panendoscopy and a cervical CT
      scan, after three courses of chemotherapy. The expression of the genes was
      determined by quantitative RT-PCR, using total RNA extracted from tumor biopsies
      taken during the initial panendoscopy. RESULTS: The means calculated, in our
      study, for the three genes of interest (TS, TP, DPD) were lower in the responder
      group than those in the non-responder group. DISCUSSION: Our preliminary findings
      reveal trends that confirm the hypothesis that the lower the level of expression
      of the sensitivity genes, the better the clinical response to chemotherapy. They
      now form part of a larger study that is currently in progress.

PMID- 21892264
TI  - Acute visual loss induced by dexamethasone during neoadjuvant docetaxol.
AB  - We present a case of a female patient who developed acute onset of visual loss
      due to central serous retinopathy as a consequence of steroid premedication for
      docetaxol given as second line neoadjuvant chemotherapy for breast cancer.
      Central serous retinopathy is a recognised association with steroids but has not
      been previously reported in association with the management of solid tumours.
      Reduction in steroid dose and duration permitted recovery of her visual acuity
      while allowing completion of the prescribed chemotherapy regimen. An overview of
      the presentation, pathogenesis, aetiologies and management of central serous
      retinopathy is given.

PMID- 21892265
TI  - Primary osteosarcoma of the right heart ventricle and atrium; a case report.
AB  - Most primary malignancies of the heart, among them also osteosarcoma are found in
      the left and very uncommonly in the right ventricle. We report a 75-year-old
      patient with a primary osteosarcoma sited in the right ventricle occluding the
      pulmonary outflow. The diagnosis was made when the patient was alive, using
      echocardiography and computerized scan tomography examinations. Like in previous
      reports on such malignancies, it was far too late for surgical or other
      therapeutic interventions, and the histological diagnosis was made post mortem.

PMID- 21892266
TI  - Molecular Mechanisms that Regulate Epidermal Growth Factor Receptor Inactivation.
AB  - The Epidermal Growth Factor Receptor (EGFR) is the prototypical receptor tyrosine
      kinase (RTK). These cell surface receptors are integral membrane proteins that
      bind ligands on their extracellular domain and relay that information to within
      the cell. The activated EGFR regulates diverse cell fates such as growth,
      proliferation, differentiation, migration, and apoptosis. These signaling
      properties are important for the appropriate development and maintenance of an
      organism. However, when inappropriately controlled, due to EGFR overexpression or
      hyperactivation, these signaling events are characteristic of many cancers. It
      remains unclear whether the uncontrolled EGFR activity leads to cell
      transformation or is a consequence of cell transformation. Regardless of the
      cause, increased EGFR activity serves both as a biomarker in the diagnosis of
      some cancers and is a molecular target for anti-cancer therapies. The promising
      results with current anti-EGFR therapies suggest that the receptor is a viable
      molecular target for a limited number of applications. However, to become an
      effective therapeutic target for other cancers that have elevated levels of EGFR
      activity, current approaches for inhibiting EGFR signaling will need to be
      refined. Here we describe the molecular mechanisms that regulate EGFR
      inactivation and discuss their potential as therapeutic targets for inhibiting
      EGFR signaling.

PMID- 21892267
TI  - Recent advances in proteomics and cancer biomarker discovery.
AB  - Early diagnosis and prevention is a key factor in reducing the mortality and
      morbidity of cancer. However, currently available screening tools lack enough
      sensitivity for early diagnosis. It is important to develop noninvasive
      techniques and methods that can screen and identify asymptomatic patients who
      have cancer. Biomarkers of cancer status can also serve as powerful tools in
      monitoring the course of cancer and in determining the efficacy and safety of
      novel therapies. Thus, discovery of novel specific biomarkers are needed that may
      provide informative clues for early diagnosis and treatment of cancer. Recently,
      remarkable progress has been made in the development of new proteomics
      technology. The progress that has been made in this field is helpful in
      identifying biomarkers that can be used for early diagnosis of cancer and
      improving the understanding of the molecular etiological mechanism of cancer.
      This article describes the current state of the art in this field.

PMID- 21892268
TI  - Molecular Cloning and Functional Characterization of Mouse alpha3(IV)NC1.
AB  - Non-collagenous alpha3 chain of type IV collagen or alpha3(IV)NC1, a 28 kDa C
      terminal domain of collagen type IV is a specific inhibitor of endothelial cell
      translation and angiogenesis. In the present study we have cloned and expressed
      mouse alpha3(IV)NC1 in baculovirus system. The recombinant protein was expressed
      in soluble form and tested for several of its biological functions. We identified
      that this recombinant mouse alpha3(IV)NC1 specifically inhibited proliferation,
      translation and tube formation of endothelial cells. Also, we show that
      alpha3(IV)NC1 treatment results in apoptosis specifically in proliferating
      endothelial cells. In addition we report for the first time that mouse
      alpha3(IV)NC1 inhibits migration and p38 MAPK phosphorylation in addition to
      inhibition of FAK/Akt/mTOR/4E-BP1 signaling. In mice alpha3(IV)NC1 treatment
      reduced tumor growth and CD-31 positive endothelial vasculature in tumors.
      Collectively, our data demonstrate the expression of biologically active form of
      mouse alpha3(IV)NC1 in Sf-9 cells and provide important mechanistic insights on
      alpha3(IV)NC1 antiangiogenic actions in endothelial cells.

PMID- 21892270
TI  - Oxaliplatin for metastatic colon cancer in a patient with renal failure.
AB  - OBJECTIVE: Oxaliplatin, a key part of the standard regimen for colorectal cancer
      in Western countries, has become available in Japan. In a hemodialysis patient
      with cecal cancer, we investigated the efficacy, safety, pharmacokinetics, and
      dialysability of oxaliplatin. METHODS: A 65-year-old man who had cecal cancer was
      treated with oxaliplatin (40 mg/m(2)) and l-leucovorin(l-LV) (200 mg/m(2)), which
      were administered simultaneously over 120 min via the side and main arms of a Y
      tube, respectively. Then 5-FU (400 mg/m(2)) was administered rapidly via the side
      tube, followed by 5-FU (2,000 mg/m(2)) over 46 hours via the main tube. The
      patient had chronic renal failure due to diabetic nephropathy and hemodialysis
      was performed 3 times a week. Blood samples were collected from the dialyzer
      before and after each hemodialysis session to examine platinum clearance.
      RESULTS: The patient received 3 courses of oxaliplatin before he died of cancer.
      During hemodialysis, the platinum level fell from 0.32 MUg/mL to 0.15 MUg/mL.
      CONCLUSION: Since patients with renal failure have various associated disorders
      and oxaliplatin has a long half-life, it is necessary to obtain more
      pharmacokinetic data to investigate its accumulation and dialysability during
      long-term treatment. Such data will assist in treating the rapidly increasing
      number of hemodialysis patients with colorectal cancer.

PMID- 21892271
TI  - Long survival in a patient with brain metastases from breast cancer.
AB  - The incidence of brain metastases (BMs) is apparently rising in patients with
      advanced breast cancer, possibly due to better therapeutic approaches for control
      of metastatic growth in other organs. Occurrence of BMs severely affects quality
      of life and is associated with dire prognosis. In this short report we describe
      the clinical case of a 47 year old woman, with BMs from breast cancer diagnosed
      in May 2001. The patient was treated with whole brain irradiation and
      radiosurgery, with initial control of BMs. Due to previous radiotherapy fields
      and doses, further local treatments are not feasible anymore. Since September
      2006, the patient has been receiving systemic therapy with Lapatinib at the dose
      of 1500 mg/die continuously, with a good control of cerebral, liver and nodal
      metastasis after one year of treatment (September 2007). Her quality of life is
      acceptable, her Karnofsky Performance Status (KPS) is more than 70%, and she
      takes care of her family, and has not experienced neuro-cognitive dysfunction.

PMID- 21892269
TI  - Oncolytic viruses: do they have a role in anti-cancer therapy?
AB  - Oncolytic viruses are replication competent, tumor selective and lyse cancer
      cells. Their potential for anti-cancer therapy is based upon the concept that
      selective intratumoral replication will produce a potent anti-tumor effect and
      possibly bystander or remote cell killing, whilst minimizing normal tissue
      toxicity. Viruses may be naturally oncolytic or be engineered for oncolytic
      activity, and possess a host of different mechanisms to provide tumor
      selectivity. Clinical use of live replicating viruses is associated with a unique
      set of safety issues. Clinical experience has so far provided evidence of limited
      efficacy and a favourable toxicity profile. The interaction with the host immune
      system is complex. An anti-viral immune response may limit efficacy by rapidly
      clearing the virus. However, virally-induced cell lysis releases tumor associated
      antigens in a 'dangerous' context, and limited evidence suggests that this can
      lead to the generation of a specific anti-tumor immune response. Combination
      therapy with chemotherapy or radiotherapy represents a promising avenue for
      ongoing translation of oncolytic viruses into clinical practice. Obstacles to
      therapy include highly effective non-specific host mechanisms to clear virus
      following systemic delivery, immune-mediated clearance, and intratumoral barriers
      limiting virus spread. A number of novel strategies are now under investigation
      to overcome these barriers. This review provides an overview of the potential
      role of oncolytic viruses, highlighting recent progress towards developing
      effective therapy and asks if they are a realistic therapeutic option at this
      stage.

PMID- 21892272
TI  - Signet-ring cell carcinoma arising in the gastric stump after
      duodenopancreatectomy for ductal adenocarcinoma of the pancreas: a case report.
AB  - The development of malignancy in the gastric stump following surgery for peptic
      ulcer disease is well recognized. There are also few reports on carcinomas
      occurring after surgery for malignant gastric disease. However, carcinoma of the
      gastric stump after duodenopancreatectomy is extremely rare. We describe what we
      believe to be an unusual case of signet-ring cell carcinoma of the gastric stump
      developing at the anastomotic site 5 years after duodenopancreatectomy for ductal
      adenocarcinoma of the pancreatic head. We performed remnant gastrectomy and Roux
      en-Y gastrojejunostomy as a curative resection. This experience clearly underlies
      that g astric stump carcinoma (GSC) may mimic metastatic disease recurrence
      leading to diagnostic confusion after surgery for malignancy. Although an
      increased risk of gastric stump carcinoma after pancreatoduodenectomy for
      pancreatic cancer has not been established, the possibility of such a
      complication should be kept in mind when evaluating patients after gastric
      resection who present with symptoms of metastatic disease recurrence years after
      the primary operation. Investigations should be independent of the entity of the
      primary disease or its localization, since GSC may well be amenable to surgical
      cure as demonstrated in the presented case. Outpatient follow up results of the
      last four years indicated no recurrence in this case.

PMID- 21892273
TI  - A hybrid lesion of lung cancer and aspergillosis.
AB  - A 74-year-old man presented with gradual wall thickening of a cystic lung lesion.
      Serologic tests indicated Aspergillus infection, but neither fungal organisms nor
      evidence of malignant disease were recovered from repeated sputum collections, a
      bronchoscopic lung biopsy specimen, or bronchial washings. Treatment with
      antifungal agents did not result in clinical improvement. Surgical resection of
      the lesion demonstrated both squamous cell carcinoma and aspergillosis. These
      distinct disorders share common radiologic manifestations that can present a
      diagnostic challenge, as in the present case.

PMID- 21892275
TI  - Thyroid carcinoma with bone metastases: a prognostic factor study.
AB  - OBJECTIVE: Occult clinical presentations usually hinder the early detection and
      management of patients with bone metastases from thyroid carcinoma. We
      retrospectively investigated the clinical outcomes of such patients from 1993 to
      2004 and analyzed the prognostic parameters. DESIGN: The basic demographic data
      and manifestations of 44 patients who had thyroid carcinoma with bone metastases
      were reviewed. We studied the gender, age, locations of metastases, histological
      types, treatment methods, hypercalcemic episodes and results of treatments. We
      used Kaplan-Meier survival analysis and log-rank tests to access the statistical
      significance. MAIN OUTCOME: The incidence of bone metastasis from thyroid
      carcinomas in this series was 5.0%. Twenty patients (45.4%) had follicular, 16
      (36.3%) had papillary, 3 (6.8%) had anaplastic, 3 (6.8%) had medullary, and 2
      (4.5%) had Hurthel cell carcinomas. Twelve patients had hypercalcemic episodes,
      ranging from 2.6 to 2.9 mmolL(-1) (mean +/- SD: 2.68 +/- 0.15 mmolL(-1)).
      Survival time after bone metastases ranged from 2 months to 8 years (mean +/- SD:
      5.3 +/- 1.3 years). The 5-year survival rate was 79.4% and the 10-year survival
      rate was 52.9%. Regarding the histological cancer type, patients with papillary
      and follicular cancers survived significantly longer than those with anaplastic
      and medullary cancers (p < 0.05). In addition, the patients presenting with
      hypercalcemia had the worst survival (p < 0.05). CONCLUSIONS: Thyroid carcinoma
      can present with bone metastases in its early stage. We found that both tumor
      type and hypercalcemia were significant prognostic factors for survival time.

PMID- 21892274
TI  - Atypical fibroxanthoma.
AB  - Atypical fibroxanthoma (AFX) is a nodular dermal ulcerative lesion with a
      favorable prognosis. AFX most commonly occurs on sun-exposed skin in elderly
      individuals. AFX is characterized by its association with ultraviolet radiation,
      not only from a clinical aspect, but also from a molecular aspect. Making a
      diagnosis of AFX is challenging, and it is important to differentiate it from
      squamous cell carcinoma and malignant melanoma. Histological features and
      combined immunohistochemical markers are necessary for a definitive diagnosis
      (i.e., an absence of immunostaining for cytokeratins, S100 and HMB45 in AFX is
      helpful for excluding both squamous cell carcinoma and malignant melanoma). AFX,
      as well as MFH (malignant fibrous histiocytoma), is a fibrohistiocytic lesion
      with myofibroblastic differentiation. AFX is considered to be a different lesion
      from MFH. AFX and MFH might share the same pathway which determines their
      morphology. However, they may have different pathways in development which
      determine their biological behavior.

PMID- 21892276
TI  - Successful downstaging of high rectal and recto-sigmoid cancer by neo-adjuvant
      chemo-radiotherapy.
AB  - PURPOSE: The benefit of neoadjuvant therapy for tumours above the peritoneal
      reflection is not clear. The purpose of this study is to demonstrate the
      feasibility and downstaging of treating locally advanced tumours from high rectum
      to distal sigmoid with preoperative chemoradiotherapy (CRT). METHODS AND
      MATERIALS: Seventeen patients with high rectal, rectosigmoid or distal sigmoid
      tumours above the peritoneal reflection received neoadjuvant CRT, selected on MRI
      findings indicating T4 disease or threatened circumferential resection margin.
      All patients were administered neoadjuvant chemotherapy, with Oxaliplatin or
      Mitomycin C and a Fluoropyrimidine. The pelvis received long-course CT-planned
      conformal RT, 45 Gy in 25 fractions, with a boost of 5.4-9 Gy in 3-5 fractions.
      Thirteen patients were treated with concomitant oral or intravenous
      Fluoropyrimidine chemotherapy. RESULTS: Median follow-up was 37 months. Overall
      survival was 82.35% (95% Confidence Interval (CI) 54.7-93.9) and disease free
      survival 81.25% (95% CI 52.5-93.5). Only 1 patient suffered loco-regional
      relapse. Chemotherapy regimens were well tolerated, though some patients required
      dose reductions. Nine patients (52.9%) lowered pathologic disease AJCC stage,
      i.e. 'downstaged'. Six patients (35.3%) achieved complete pathological response.
      Clear margins were attained in all but 1 patient. Three patients were converted
      from cT4 to ypT3. No patient required a gap during CRT. One patient suffered a
      grade III acute toxicity, but no grade IV (RTOG). There were 3 grade III and 3
      grade IV late toxicities (LENT-SOMA). CONCLUSIONS: Locally advanced high rectal
      and recto-sigmoid tumours may be treated with pre-operative CRT with acceptable
      toxicity, impressive down-staging, and clear surgical margins.

PMID- 21892277
TI  - Malignant struma ovarii: good response after thyroidectomy and I ablation
      therapy.
AB  - BACKGROUND: Malignant struma ovarii is a rare malignant germ cell tumor of the
      ovary. Due to the rarity of this disease, treatment has not been uniform
      throughout the published literature. CASES: We present three cases of malignant
      struma ovarii. Following primary surgery, all were subsequently treated with
      thyroidectomy and (131)I ablation therapy, two patients as first line management,
      one following the occurrence of metastatic disease. CONCLUSION: Histological
      diagnosis of malignant struma ovarii is similar to that of well differentiated
      thyroid carcinoma (WDTC). In line with the latest advice on treatment of WDTC, we
      believe that the best option for patients with malignant struma ovarii is
      surgical removal of the ovarian lesion followed by total thyroidectomy which
      allows the exclusion of primary thyroid carcinoma, and in addition, allows
      radioiodine ((131)I) ablation therapy for (micro) metastasis. After
      thyroidectomy, thyroglobulin can be used as a tumor marker for follow-up.
      Moreover, nuclear medicine imaging using radioiodine ((123)I) can be performed to
      demonstrate metastatic carcinoma. A multidisciplinary approach is essential.

PMID- 21892278
TI  - Primary MALT Type Skin Lymphoma-Is 'Wait and See' a Possible Strategy?
AB  - Primary cutaneous lymphomas are the second most common site of extranodal non
      Hodgkin lymphoma. A specifically type named extranodal marginal zone B-cell
      lymphomas are indolent low-grade neoplasma.We report a case of a 42-year-old
      white man with multiple subcutaneous tumors located on the trunk and neck. The
      histopathological exam showed a non-epidermotropic, dense lymphocytic infiltrate.
      Histologic, immunohistochemical and cytologenetic analysis diagnosed primary
      cutaneous B-cell lymphoma MALT type. Investigation for other extranodal MALT
      lymphoma gastrointestinal tract, lung, salivary and thyroid glands was negative.
      The patient refused radiotherapy, but he accepted every 6 months close follow-up.
      Over a seven years period, we noticed a progressively disappearance of the skin
      lesions.The necessity of aggressive treatment of this disease with excellent
      prognosis is discussed.The treatment necessity of primary cutaneous B-cell
      lymphoma MALT type is discussed.

PMID- 21892279
TI  - Integrated FDG PET/CT: Utility and Applications in Clinical Oncology.
AB  - Accurate diagnosis and staging are essential for an optimal management of cancer
      patients. Positron emision tomography with 2-deoxy-2-fluorine-18-fluoro-D-glucose
      ((18)FDG-PET) and, more recently, (18)FDG-PET/computed tomography ((18)FDG
      PET/CT) have emerged as powerful imaging tools in oncology, because of the
      valuable functional information they provide. The combined acquisition of PET and
      CT has synergistic advantages over its isolated constituents and minimizes their
      limitations. It decreases examination times by 25%-40%, leads to a higher patient
      throughput and unificates two imaging procedures in a single session. There is
      evidence that (18)FDG-PET/CT is a more accurate test than either of its
      components for the evaluation of various tumors. It is a particularly valuable
      tool for detection of recurrence, especially in asymptomatic patients with rising
      tumor markers and those with negative or equivocal findings on conventional
      imaging tests. Yet, there are some limitations and areas of uncertainty, mainly
      regarding the lack of specificity of the (18)FDG uptake and the variable (18)FDG
      avidity of some cancers. This article reviews the advantages, limitations and
      main applications of (18)FDG-PET/CT in oncology, with especial emphasis on lung
      cancer, colorectal cancer, lymphomas, melanoma and head and neck cancers.

PMID- 21892280
TI  - Review: mitochondrial defects in breast cancer.
AB  - Mitochondria play important roles in cellular energy metabolism, free radical
      generation, and apoptosis. Mitochondrial DNA has been proposed to be involved in
      carcinogenesis because of its high susceptibility to mutations and limited repair
      mechanisms in comparison to nuclear DNA. Breast cancer is the most frequent
      cancer type among women in the world and, although exhaustive research has been
      done on nuclear DNA changes, several studies describe a variety of mitochondrial
      DNA alterations present in breast cancer. In this review article, we to provide a
      summary of the mitochondrial genomic alterations reported in breast cancer and
      their functional consequences.

PMID- 21892282
TI  - Molecular determinants of glioblastoma response to epidermal growth factor
      receptor kinase inhibitors.

PMID- 21892281
TI  - Signal transduction involving the dmp1 transcription factor and its alteration in
      human cancer.
AB  - Dmp1 (cyclin D-interacting myb-like protein 1; also called Dmtf1) is a
      transcription factor that has been isolated in a yeast two-hybrid screen through
      its binding property to cyclin D2. Dmp1 directly binds to and activates the Arf
      promoter and induces Arf-p53-dependent cell cycle arrest in primary cells. D-type
      cyclins usually inhibit Dmp1-mediated transcription in a Cdk-independent fashion;
      however, Dmp1 shows synergistic effects with D-cyclins on the Arf promoter. Ras
      or Myc oncogene-induced tumor formation is accelerated in both Dmp1(+/-) and
      Dmp1(-/-) mice with no significant differences between Dmp1(+/-) and Dmp1(-/-).
      Thus, Dmp1 is haplo-insufficient for tumor suppression. Tumors from Dmp1(-/-) or
      Dmp1(+/-) mice often retain wild-type Arf and p53, suggesting that Dmp1 is a
      physiological regulator of the Arf-p53 pathway. The Dmp1 promoter is activated by
      oncogenic Ras-Raf signaling, while it is repressed by physiological mitogenic
      stimuli, overexpression of E2F proteins, and genotoxic stimuli mediated by NF
      kappaB. The human DMP1 gene (hDMP1) is located on chromosome 7q21 and is
      hemizygously deleted in approximately 40% of human lung cancers, especially those
      that retain normal INK4a/ARF and P53 loci. Thus, hDMP1 is clearly involved in
      human carcinogenesis, and tumors with hDMP1 deletion may constitute a discrete
      disease entity.

PMID- 21892283
TI  - Pemetrexed, Carboplatin, and Concomitant Radiation followed by Surgery for
      Locally Advanced Esophageal Cancer: Results of a Planned Interim Toxicity
      Analysis of North Central Cancer Treatment Group Study N044E.
AB  - PURPOSE: This brief report describes a planned, interim, 6-patient toxicity
      analysis that confirms the safety of pemetrexed, carboplatin, radiation with
      subsequent surgery, as prescribed in the North Central Cancer Treatment Group
      trial N044E, in patients with locally advanced esophageal cancer. METHODS: Six
      patients with locally advanced, potentially resectable esophageal cancer received
      pemetrexed 500 mg/m(2) and carboplatin AUC = 6 on days 1 and 22 with 5040
      centigray of concomitant radiation in 28 fractions over 5.5 weeks followed by
      esophagectomy as a prelude to a phase II multi-institutional trial. RESULTS: Only
      1 of the 6 patients experienced a grade 4 adverse event (neutropenia). This
      patient also experienced a grade 3 depression. Of the remaining 5 patients, three
      experienced at least one grade 3 adverse event (neutropenia, nausea/vomiting, and
      esophagitis). There were no deaths. Incidentally, one patient manifested a
      complete pathologic response, three a partial pathologic response, and one stable
      disease. CONCLUSION: These preliminary observations on safety suggest that this
      regimen can be further studied in this clinical setting.

PMID- 21892284
TI  - Pre-operative Concomitant Radio-chemotherapy in Bulky Carcinoma of the Cervix: A
      Single Institution Study.
AB  - OBJECTIVE: To evaluate the treatment results of patients (pts) with FIGO stage
      IB2, IIA, IIB cervical carcinoma (CC) treated with pre-operative radio
      chemotherapy, followed by extended radical hysterectomy. METHODS: Retrospective
      study of 148 women treated to the Institut Curie for operable FIGO Stage IB2 to
      IIB, biopsy proved CC. Among them, 70 pts, median age 46 years, were treated
      using the same regimen associating primary radio-cisplatinum based chemotherapy,
      intracavitary LDR brachytherapy, followed by extended radical hysterectomy.
      Kaplan-Meier estimates were used to draw survival curves. Comparisons of survival
      distribution were assessed by the log-rank test. RESULTS: Complete histological
      local-regional response was obtained in 56% of the pts (n = 39). Residual
      macroscopic or microscopic disease in the cervix was observed in 28 pts (40%).
      All but one had in-situ microscopic residual CC. Lateral residual disease in the
      parametria was also present in 9 pts, all with residual CC. Pelvic lymph nodes
      were free from microscopic disease in 56 pts (80%). Eight of 55 (11%)
      radiological N0 patients had microscopic nodal involvement, as compared to 6/15
      (40%) radiological N1 (p = 0.03). Seventeen pts (25%) had residual cervix disease
      but negative nodes. After median follow-up of 40 months (range, 8-141), 38/70
      patients (54.1%) are still alive and free of disease, 6 (8.6%) alive with
      disease, and 11 (15.8%) patients were lost for follow-up but free of disease. IN
      CONCLUSION: The treatment of locally advanced CC needs a new multidisciplinary
      diagnostic and treatment approach using new therapeutic arms to improve the
      survival and treatment tolerance among women presenting this disease.

PMID- 21892285
TI  - Therapeutic anti-tumor vaccines: from tumor inhibition to enhancement.
AB  - Numerous immunization trials have proved successful in preventing the growth of
      experimental animal tumors and human hepatocarcinomas induced by hepatitis B
      virus. These results have prompted researchers and physicians to use vaccines in
      a therapeutic mode but the results have, in general, been disappointing even when
      strongly immunogenic murine tumors were concerned. Data presented herein suggest
      that immunotherapy induced by a single dose of a dendritic cell-based vaccine
      against a murine established tumor or against residual tumor cells after
      debulking the primary tumor, can render not only inhibitory or null but also
      stimulatory effects on tumor growth. These different effects might be dependent
      on where the system is located in the immune response curve that relates the
      quantity of the immune response to the quantity of target tumor cells. We suggest
      that high ratios render tumor inhibition, medium and very low ratios render null
      effects and low ratios-between medium and very low ones-render tumor stimulation.
      Since the magnitude of these ratios would depend on the antigenic profile of the
      tumor, the immunogenic strength of the vaccine used and the immunological state
      of the host, studies aimed to determine the magnitude of these variables in each
      particular case, seem to be necessary as a pre-condition to design rational
      immunotherapeutic approaches to cancer. In contrast, if these studies are
      neglected, the worst thing that an immunotherapist could face is not merely a
      null effect but enhancement of tumor growth.

PMID- 21892286
TI  - Renal Cell Carcinoma with IVC Thrombi; Current Concepts and Future Perspectives.
AB  - The incidence of venous extension to the inferior vena cava (IVC) in renal cell
      carcinoma (RCC) is markedly increased recently mostly due to the advances in
      diagnostic modalities. Such vascular invasion implies a heightened biologic
      behavior and a surgical challenge during the course of treatment. In this study,
      we reviewed the classification guidelines, recent diagnostic tools and up-to-date
      therapeutic modalities for RCC with IVC tumor thrombi added to the prognostic
      significance regarding the pathologic nature of vascular invasion; cephalad
      extent of thrombi and any associated distant metastasis. Also, we are providing
      our suggestion regarding the use of angioscopy for removal of IVC thrombi in a
      relatively bloodless field without aggressive surgical manipulations or shunt
      techniques for maintenance of hemodynamic stability.

PMID- 21892287
TI  - Bead-selected antitumor genetic cell vaccines.
AB  - Cancer vaccines have always been in the scope of gene therapy research. One of
      the most successful approaches has been working with genetically modified tumor
      cells. However, to become a clinical reality, tumor cells must suffer a long and
      risky process from the extraction from the patient to the reimplantation as a
      vaccine. In this work, we explain our group's approach to reduce the cell number
      required to achieve an immune response against a melanoma murine model, employing
      bead-selected B16 tumor cells expressing GM-CSF and B7.2.

PMID- 21892288
TI  - The Relationship Between MR Demonstration of Extramural Venous Invasion and Nodal
      Disease in Rectal Cancer.
AB  - PURPOSE: To investigate the relationship between extramural venous invasion
      (EMVI) detected at T2-weighted MRI and nodal disease rectal cancer compared with
      histopathology. MATERIALS AND METHODS: The MR imaging of 79 consecutive patients
      with rectal cancer who underwent primary rectal surgery without neoadjuvant
      treatment were reviewed. MR images were scored by an expert radiologist for the
      presence and degree of EMVI using a five point scale blinded to pathological
      findings. Receiver operating characteristic curve analyses were performed to
      determine the sensitivity and specificity of MRI scoring in predicting EMVI and
      nodal disease at histopathology. RESULTS: Compared with histology, an MR score of
      >2 was found to have 100% sensitivity (95% CI: 77%-100%) and 89% specificity (95%
      CI: 79%-96%) in identifying EMVI involving veins >3 mm in diameter. An EMVI score
      of >2 was had a sensitivity of 56% (95% CI: 30%-80%) and specificity of 81% (95%
      CI: 69%-90%) for identifying patients with stage N2 disease. CONCLUSIONS: EMVI
      score of >2 on T2-weighted MR imaging has a high sensitivity and specificity for
      histopathologically proven extramural venous invasion involving venules >=3 mm in
      diameter. However, EMVI scores have only moderate sensitivity in the predicting
      nodal involvement.

PMID- 21892290
TI  - Evaluation of Image Enhancement Method on Target Registration Using Cone Beam CT
      in Radiation Therapy.
AB  - An intensity based six-degree image registration algorithm between cone-beam CT
      (CBCT) and planning CT has been developed for image-guided radiation therapy
      (IGRT). CT images of an anthropomorphic chest phantom were acquired using
      conventional CT scanner and corresponding CBCT was reconstructed based on
      projection images acquired by an on-board imager (OBI). Both sets of images were
      initially registered to each other using attached fudicial markers to achieve a
      golden standard registration. Starting from this point, an offset was applied to
      one set of images, and the matching result was found by a gray-value based
      registration method. Finally, The registration error was evaluated by comparing
      the detected shifts with the known shift. Three window-level (WL) combinations
      commonly used for image enhancement were examined to investigate the effect of
      anatomical information of Bony only (B), Bone+Tissue (BT), and Bone+Tissue+Air
      (BTA) on the accuracy and robustness of gray-value based registration algorithm.
      Extensive tests were performed in searching for the attraction range of
      registration algorithm. The widest attraction range was achieved with the WL
      combination of BTA. The average attraction ranges of this combination were 73.3
      mm and 81.6 degree in the translation and rotation dimensions, respectively, and
      the average registration errors were 0.15 mm and 0.32 degree. The WL combination
      of BT shows the secondary largest attraction ranges. The WL combination of B
      shows limited convergence property and its attraction range was the smallest
      among the three examined combinations (on average 33.3 mm and 25.0 degree). If
      two sets of 3D images in original size (512 * 512) were used, registration could
      be accomplished within 10~20 minutes by current algorithm, which is only
      acceptable for off-line reviewing purpose. As the size of image set reduced by a
      factor of 2~4, the registration time would be 2~4 minutes which is feasible for
      on-line target localization.

PMID- 21892289
TI  - Multiple Myeloma Includes Phenotypically Defined Subsets of Clonotypic CD20+ B
      Cells that Persist During Treatment with Rituximab.
AB  - Potential progenitor B cell compartments in multiple myeloma (MM) are clinically
      important. MM B cells and some circulating MM plasma cells express CD20,
      predicting their clearance by treatment with anti-CD20. Here we describe two
      types of clonotypic CD20+ B cell in peripheral blood of myeloma patients,
      identified by their expression of CD19 and CD20 epitopes, their expression of
      CD45RA and their light scatter properties. Thus, the circulating component of the
      MM clone includes at least two distinct CD19+ CD20+ B cell compartments, as well
      as CD138+ CD20+ plasma cells. To determine whether either or both B cell subsets
      and the CD20+ plasma cell subset were depleted by anti-CD20 therapy, they were
      evaluated before, during and after treatment of patients with rituximab (anti
      CD20), followed by quantifying B cell subsets over a 5 month period during and
      after treatment. Overall, all three types of circulating B lineage cells persist
      despite treatment with rituximab. The inability of rituximab to prolong survival
      in MM may result from this failure to deplete CD20+ B and plasma cells in MM.

PMID- 21892291
TI  - The effect of docetaxel (taxotere) on human gastric cancer cells exhibiting low
      dose radiation hypersensitivity.
AB  - Low-dose radiation hypersensitivity (HRS) describes a phenomenon of excessive
      sensitivity to X ray doses <0.5 Gy. Docetaxel is a taxane shown to arrest cells
      in the G(2)/M phase of the cell cycle. Some previous studies suggested that HRS
      might result from the abrogation of the early G(2) checkpoint arrest. First we
      tested whether HRS occurs in gastric cancer-derived cells, and whether pre
      treatment of cells with low docetaxel concentrations can enhance the magnitude of
      HRS in gastric cancer cells. The results demonstrated HRS at ~0.3 Gy and the
      synergy between 0.3 Gy and docetaxel (3 nM for 24 h), and the additivity of other
      drug/dose combinations. The synergistic effect was associated with a significant
      docetaxel-induced G(2) accumulation. Next, we evaluated in time-course
      experiments ATM kinase activity and proteins associated with the induction and
      maintenance of the early G(2) checkpoint. The results of multi-immunoblot
      analysis demonstrate that HRS does not correlate with the ATM-dependent early
      G(2) checkpoint arrest. We speculate that G(2) checkpoint adaptation, a
      phenomenon associated with a prolonged cell cycle arrest, might be involved in
      HRS. Our results also suggest a new approach for the improvement the
      effectiveness of docetaxel-based radiotherapy using low doses per fraction.

PMID- 21892292
TI  - A unique complication associated with concurrent chemoradiation for the treatment
      of locally advanced head and neck cancer.
AB  - BACKGROUND: Concurrent chemoradiation is becoming an increasingly popular
      treatment for patients with locally advanced head and neck cancer. The full
      extent of treatment related complications has not been completely documented in
      the literature. METHODS: We present the case of a patient treated with definitive
      intensity modulated radiation therapy and concurrent carboplatin and fluorouracil
      for a locally advanced oral cavity and base of tongue cancer. RESULTS: The
      patient suffered acute grade 4 dermatitis and mucositis during treatment. One
      month after completion of treatment, the patient was found to have permanent
      adherence of the tongue to the buccal mucosa as a result of severe scar tissue
      formation. CONCLUSIONS: As more patients undergo chemoradiation for the treatment
      of locally advanced head and neck cancer, the full extent of treatment related
      complications are being identified. To our knowledge, this is the first report of
      chemoradiation for head and neck cancer resulting in adherence of the tongue to
      the buccal mucosa.

PMID- 21892293
TI  - Radionuclide Imaging of Apoptosis in Malignancies: Promise and Pitfalls of Tc
      Hynic-rh-Annexin V Imaging.
AB  - Radionuclide detection of apoptosis with of (99m)Tc-Hynic-rh-Annexin V
      scintigraphy is an effective tool for in vivo visualisation and monitoring of
      apoptosis in various malignant tumour. Early therapy-induced increase of the
      tumour tracer uptake correlates with favourable outcome, whereas stable or
      decreased uptake correlates with stable disease or tumour progression. Therefore
      sequential (99m)Tc-Hynic-rh-Annexin V scintigraphy could be used to predict
      therapy outcome on a patient-to-patient basis within 48 hours after the start of
      treatment. However, moderate tumour-to-background ratio and therapy-induced
      changes in normal tissues could confound image analysis. To assure accurate
      interpretation of Annexin V scans, the awareness of the biophysiological and
      biochemical properties contributing to the tracer distribution is essential. In
      with manuscript we discuss the patterns of Annexin V tumour uptake and illustrate
      the most frequent pitfalls associated with Annexin V imaging in correlation with
      CT and MRI imaging.

PMID- 21892294
TI  - A comparison of merkel cell carcinoma and melanoma: results from the california
      cancer registry.
AB  - INTRODUCTION: Melanoma and Merkel cell carcinoma (MCC) are both aggressive skin
      malignancies associated with immunosuppression and possible UV exposure. Both
      tumors get similar surgical treatment; however, MCC is a relatively rare tumor in
      which less is known about prognosis and clinical behavior. METHODS: The
      California Cancer Registry (CCR), a population-based registry, was reviewed from
      the years 1988-2003. Merkel cell carcinoma and melanoma were compared with
      relation to gender, age, ethnicity, disease stage, site, and survival. RESULTS: A
      total of 113,187 cases of melanoma and 1,878 cases of MCC were identified in the
      CCR. Though both cancers are more common in men than in women, MCC had a higher
      incidence in men than melanoma (63% vs 57% p < 0.005). MCC occurs in the more
      elderly, with 73.6% of cases occurring in people over 70 years. In contrast, 69%
      of melanoma cases occurred in people younger than 70 years (p < 0.005). MCC shows
      a predilection for the head and neck compared to melanoma (47% vs 25.8%)
      Additionally, melanoma occurs more frequently on the trunk than MCC (30% vs
      8.7%). Finally, the 10-year cumulative survival is lower for MCC than for
      melanoma (17.7% vs 61.3%, p < 0.005). CONCLUSION: Many clinicians assume MCC and
      melanoma behave similarly. However, MCC occurs in an older population, more
      frequently on the head and neck, in a higher percentage of men. Additionally, MCC
      has a higher rate of regional metastasis and thus may have more of a benefit from
      regional staging procedures. Overall, MCC has a worse prognosis.

PMID- 21892296
TI  - A comparison of clinicopathological features and molecular markers in british and
      nigerian women with breast cancer.
AB  - BACKGROUND: Some studies have suggested that breast cancer in black women is more
      aggressive than in white women. This study's aim was to look for evidence of
      differences in tumour biology between the two cohorts. METHODS: This study
      compared the stage, grade and pathological expression of five immunohistochemical
      markers (oestrogen receptor [ER], progesterone receptor [PR], ERBB2, P53 and
      cyclin D1 [CCND1]) in tumour biopsies from age-matched cohorts of patients from
      Nigeria and England. Sixty-eight suitable samples from Nigerian (n = 34) and
      British (n = 34) breast cancer patients were retrieved from histology tissue
      banks. RESULTS: There were significant differences between the two cohorts in the
      expression of ER and CCND1; and stark differences in the clinical stage at
      presentation. But no significant differences were observed for tumour grade.
      CONCLUSION: There was a significantly, low ER expression in the Nigerian cases
      which also predicts a poor response to hormonal therapy as well as a poorer
      prognosis. Differences in clinical stage at presentation will most likely
      influence prognosis between Nigerian and British women with breast cancer.

PMID- 21892295
TI  - HSP70s: From Tumor Transformation to Cancer Therapy.
AB  - Heat shock proteins (HSPs) are a defined set of chaperones for maintaining proper
      functions of proteins. The HSP70 family, one of the most inducible families in
      response to stress, protects cells from stress-induced cell death. It has been
      documented that HSP70s are highly expressed in various types of cancer cells and
      make the cells resistant to adverse microenvironments, such as hypoxia and
      glucose starvation, which are common features in malignant progression. Over
      expression of HSP70s is thus associated with tumor transformation and eventually
      results in a decrease of chemotherapy efficacy. Notably, the distribution of
      HSP70s is deregulated in cancer cells. It has been reported that HSP70s localize
      distinct organelles or are exported to humoral circulation during cancer
      development. Either surface or exported HSP70s play danger signals and trigger
      immune response to destroy the tumor cells. In this review, we lay out recent
      advances in the HSP70s-mediated cancer diagnosis and therapy. This review would
      be enlightening for clinical cancer medicine.

PMID- 21892297
TI  - Primary adrenal leiomyosarcoma: a case report and literature review.
AB  - The case presented here illustrates a 75 year old female patient who underwent
      surgical resection of a right adrenal mass of uncertain nature. The final
      histological diagnosis was consistent with leiomyosarcoma arising from the
      adrenal anatomic site.PRIMARY LEIOMYOSARCOMA OF THE ADRENAL GLAND IS A VERY RARE
      MALIGNANT MESENCHYMAL NEOPLASM: to our knowledge, this is only the twelfth case
      reported in literature.We describe the clinical course and a brief review of
      clinical and histological features, biologic behaviour, diagnostic approaches and
      therapeutic strategies.

PMID- 21892298
TI  - The 'Pokemon' (ZBTB7) Gene: No Evidence of Association with Sporadic Breast
      Cancer.
AB  - It has been proposed that the excess of familiar risk associated with breast
      cancer could be explained by the cumulative effect of multiple weakly
      predisposing alleles. The transcriptional repressor FBI1, also known as Pokemon,
      has recently been identified as a critical factor in oncogenesis. This protein is
      encoded by the ZBTB7 gene. Here we aimed to determine whether polymorphisms in
      ZBTB7 are associated with breast cancer risk in a sample of cases and controls
      collected in hospitals from North and Central Spanish patients. We genotyped 15
      SNPs in ZBTB7, including the flanking regions, with an average coverage of 1
      SNP/2.4 Kb, in 360 sporadic breast cancer cases and 402 controls. Comparison of
      allele, genotype and haplotype frequencies between cases and controls did not
      reveal associations using Pearson's chi-square test and a permutation procedure
      to correct for multiple test. In this, the first study of the ZBTB7 gene in
      relation to, sporadic breast cancer, we found no evidence of an association.

PMID- 21892300
TI  - Octreotide in Palliative Treatment of Unresectable Cholangiocarcinoma: Is it
      Effective for Disease Stabilization?

PMID- 21892299
TI  - Should we consider cancers as embryonic diseases or as consequences of stem-cell
      deregulation?
AB  - Cancers have long been described as the result of successive selections of
      somatic cells progressively acquiring growth and survival advantages. Such a
      model was hardly compatible with the obvious heterogeneity of the cancer cell
      population present in tumors. This heterogeneity rather suggests that mutations
      hint multipotent cells that, in addition to the resulting proliferation and
      survival advantages, display differentiation capabilities. Adult stem cells or
      progenitors display similar properties, supporting the concept that cancers
      actually originate from these cells. The recent observation that differentiated
      cells can dedifferentiate and acquire stemness properties suggests an alternative
      and additional explanation for the origin of "cancer-initiating" cells and
      reopens the debate of the contribution of somatic cells to cancer progression.

PMID- 21892301
TI  - Leptomeningeal metastases in a patient with an extragonadal germ cell tumor.
AB  - We present a case of leptomeningeal metastases in a 30-year-old man with an
      extragonadal germ cell tumor. The patient was referred to our hospital for
      treatment of an occipital brain metastasis. This lesion was resected, followed by
      whole brain radiotherapy and further chemotherapy, and a temporary complete
      remission was achieved. However, leptomeningeal recurrence developed, and despite
      salvage chemotherapy, the patient died of disease. Although multidisciplinary
      treatment is given to treat brain metastases of germ cell tumors, the patients'
      prognosis has been unsatisfactory. The identification of a standard/effective
      treatment is required.

PMID- 21892302
TI  - Phase II Study of S-1 Monotherapy as a First-line, Combination Therapy of S-1
      plus Cisplatin as a Second-line, and Weekly Paclitaxel Monotherapy as a Third
      line Therapy in Patients with Advanced Gastric Carcinoma: Phase II Study of S-1,
      S-1 plus Cisplatin, and Weekly Paclitaxel in Patients with Advanced Gastric
      Carcinoma.
AB  - BACKGROUND: We conducted a pilot phase II study to evaluate the efficacy and
      safety of S-1 as a first-line, S-1 plus cisplatin as a second-line, and weekly
      paclitaxel as a third-line therapy for advanced gastric cancer. PATIENTS AND
      METHODS: Between 2002 and 2005, 19 patients were enrolled in this study.
      Chemotherapy consisted of either 60 mg/m(2) of S-1 for 4 weeks at 6 weeks
      interval, a combination of 60 mg/m(2) S-1 for 3 weeks and 60 mg/m(2) cisplatin on
      day 8 at 5 weeks interval, or 60 mg/m(2) paclitaxel at day 1, 8, 15, at 4 weeks
      interval. The regimen was repeated until the occurrence of unacceptable
      toxicities, disease progression, or patient refusal. The primary end point was
      the overall survival. RESULTS: The response rates were 33.3%, 12.5%, and 0% after
      the first, second, and third line chemotherapy, respectively. The mean overall
      survival time was 994 days. The median survival time could not be calculated
      because 12 out of 19 patients were still alive when the study was concluded.
      Regarding hematological toxicity, the major adverse effect was leukopenia, which
      reached grades 3-4 in all lines of chemotherapy investigated. In addition,
      regarding non-hematological toxicities, the major adverse effect was anorexia,
      which reached grade 3-4 in the second line chemotherapy, and no deaths were
      attributable to the adverse effects of the drugs. CONCLUSION: This sequential
      therapy was an effective treatment for advanced gastric cancer with acceptable
      toxic side-effects. We considered this sequential therapy to be effective because
      of the smooth switch to the next regimen.

PMID- 21892303
TI  - Multidisciplinary approach in managing orbital tumors in ibadan, Nigeria.

PMID- 21892304
TI  - Unusual malignant transformation of recurrent sebaceoma. A case report.
AB  - Sebaceoma is a benign tumor composed of incompletely differentiated sebaceous
      cells of varying degrees of maturity. Sebaceomas was never reported as a known
      premalignant lesion.This is a report of a sixteen year old boy who presented with
      a malignant transformation of a recurrent sebaceoma which was excised twice by
      Moh's surgery. Excision was done with a free margin of 1 cm down to the parotid
      fascia. Reconstruction was performed on the same set by using cervicofascial flap
      extending down to the supra-clavicular area. The patient had an uneventful
      postoperative period apart from distal marginal necrosis of the flap, which
      healed nicely with conservative measures and daily dressing and was sent to our
      cancer centre to start his adjuvant radiotherapy.Previous literature stated that
      sebaceoma is a distinctive benign tumor. We have presented a case of an unusual
      malignant transformation of a preauricular recurrent sebaceoma. This indicates
      that sebaceoma does have a potential risk of malignant transformation. We believe
      that managing recurrent sebaceoma more aggressively with wide local excision and
      postoperative adjuvant radiotherapy would provide better prognosis.

PMID- 21892305
TI  - Darbepoetin versus epoetin alfa for the correction of anemia in cancer patients
      receiving radiotherapy or chemoradiotherapy treatment.
AB  - INTRODUCTION: Anemia is the most frequent hematological disturbance in cancer
      patients, with prevalence between 30% and 90%, depending on the type of tumor,
      the antitumor treatment, and other factors (infection, malnutrition, bleeding,
      tumor infiltration of the bone marrow). A number of erythropoietic agents have
      shown to be effective in increasing the hemoglobin (Hb) levels, reducing the
      requirements for transfusion, and improving quality of life. The objective of
      this study is to compare darbepoetin alfa and epoetin alfa when used to correct
      anemia in cancer patients who are receiving radiotherapy or radiochemotherapy.
      MATERIAL AND METHODS: A prospective study of 125 consecutive patients with anemia
      (Hb <13 g/dL in males or <12 g/dL in females) who were undergoing treatment with
      radiotherapy (RT) or radiochemotherapy (RCT) in our department were enrolled
      between March 2003 and March 2005. The treatment for the anemia was either
      darbepoetin alfa 150 mcg/week (62 patients, group 1) or epoetin alfa 40,000
      IU/week (63 patients, group 2). Patients received iron supplements in both
      groups. Treatment was administered in a consecutive manner depending on tumor
      type. If the increase in Hb was <1 g/dL after 4 weeks of treatment, the dose was
      increased to 300 mcg/week in group 1 or to 60,000 IU/week in group 2. The
      treatment was terminated when a Hb value of >=15 g/dL was reached during RT
      treatment, a Hb value of >=14 g/dL was reached if the RT had been completed, or
      after 16 weeks of treatment whatever the Hb value. The mean age of patients was
      63.36 +/- 11.27 years, 67% were male. No significant differences were observed
      between the 2 groups in tumor type or stage, previous treatments, or intent to
      treat with RT or RCT. RESULTS: Comparing group 1 and group 2 by intent to treat,
      the mean Hb at the start of treatment with the study drug was 12.1 g/dL vs 11.8
      g/dL, the proportion of patients whose dose was increased was 19.7% vs 24.6%, the
      need for transfusion was 3.2% in each group, the duration of erythropoietic
      treatment was 6.5 weeks in both groups, and 2 patients in group 2 restarted
      treatment with epoetin alfa. The percentage of patients who responded (defined as
      an increase in the Hb >= 2 g/dL in the absence of transfusions) was of 72.6% and
      66.7%, respectively. Four vascular adverse events were observed, 2 in each group.
      No significant differences were observed with respect to the baseline, week 4,
      and week 12 levels of endogenous erythropoietin, serum iron,% saturation, and
      ferritin. The increase in Hb 1 month after the final administration of the study
      drug was 2.21 g/dL in group 1 and 2.46 g/dL in group 2 (p = ns). CONCLUSIONS: The
      results of our study demonstrate that both treatments are equally effective in
      correcting anemia in cancer patients undergoing RT or RCT.

PMID- 21892306
TI  - Octreotide in Palliative Treatment of Hepatic Metastases: Is it Effective for
      Clinical Stabilization?

PMID- 21892308
TI  - Response of cutaneous metastases from breast cancer to capecitabine.

PMID- 21892307
TI  - Pancreas cancer survival in the gemcitabine era.
AB  - After multiple positive studies, gemcitabine, approved for the treatment of
      pancreas cancer by the FDA in 1977, became standard of care. Whether this
      therapeutic advance has translated into longer survival for pancreas cancer
      patients in general has not been established. This study, derived from SEER
      (Surveillance, Epidemiology, and End Results (SEER) Program of the National
      Cancer Institute) data, compared the survival experiences of the gemcitabine
      (1998-2004) and pre-gemcitabine (1988-1997) eras for 7,151 patients who had
      metastatic disease and did not undergo extirpative surgery, 14,369 patients who
      had not undergone surgery and had metastases, 5,042 patients who had undergone
      surgery and did not have metastases, and 5,011 patients who had undergone surgery
      and had metastases. Calculated survival time ratios (TR) were adjusted for
      radiotherapy history, grade, nodal status, loco-regional extent of disease, age,
      race, and gender. For those who did not undergo extirpative surgery, improvements
      in survival in the gemcitabine era (1998-2004) versus the prior time period (1988
      1997) seen for patients with metastatic cancer (TR = 1.20, 95% c.i. 1.15-1.25)
      were not seen for those without metastatic cancer (TR = 1.05, 95% c.i. 1.00
      1.15). For those who did undergo extirpative surgery, improvements were much more
      dramatic for those with metastatic cancer (TR = 1.61, 95% c.i. 1.45-1.80) than
      those without metastases (TR = 1.23, 95% c.i. 1.15-1.31). The results are
      consistent with the notion that the promising findings with respect to
      gemcitabine in the controlled clinical trials have found expression in the
      general population of patients with pancreas cancer.

PMID- 21892309
TI  - Chromosome 1p and 11q deletions and outcome in neuroblastoma-a critical review.

PMID- 21892310
TI  - Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma-a
      critical review.

PMID- 21892311
TI  - Effect of thiazolidinediones on the erythropoeitic and germinal cells in the male
      wistar rats.
AB  - Hyperglycemia is the main determinant of long term diabetic complications mainly
      through induction of oxidative stress responsible for secondary defects including
      cancer, infertility etc. Thiazolidinediones (TZDs) are known to posses the
      antioxidant potential against the reactive oxygen species. The ability of
      clinically used TZDs like Rosiglitazone (RSG) and Pioglitazone (PIO) in diabetic
      complications is still need to be studied extensively in the literature. In this
      study, the role of RSG and PIO on the frequency of nuclear and germinal cell
      damage was studied using bone marrow micronucleus (MN) test, sperm shape
      abnormality and sperm count in normal animals. The drugs were tested in the three
      doses (1, 10 and 100 mg/kg) after acute (48 hrs and 72 hrs) and chronic (4 weeks)
      treatment. The results indicated that RSG has produced significant (p < 0.01)
      decrease in P/N (polychromatic and normochromatic erythrocytes) ratio at 10 and
      100 mg/kg without affecting the frequency of micronucleated erythrocytes, sperm
      shape morphology and sperm count. PIO in the tested doses did not induce any
      change in P/N ratio and sperm count but the higher dose (100 mg/kg) showed
      suppression of MN in normochromatic erythrocytes and % sperm shape abnormality
      compared to the control group.

PMID- 21892312
TI  - Experimental antioxidant therapy in ataxia telangiectasia.
AB  - Ataxia telangiectasia (AT) is a rare genetic disorder characterized by
      immunodeficiency, early onset neurological degeneration, hypersensitivity to
      ionizing radiation and a high incidence of lymphoid cancers. The disease results
      from bi-allelic mutations in the AT mutated (ATM) gene involved in cell cycle
      checkpoint control and repair of DNA double-strand breaks. Evidence has been
      accumulating that oxidative stress is associated with AT and may be involved in
      the pathogenesis of the disease. This led to a hypothesis that antioxidant
      therapy may mitigate the symptoms of AT, especially neurological degeneration and
      tumorigenesis. Consequently, several studies examined the effect of antioxidants
      in Atm deficient mice used as an animal model of AT. N-acetyl-L-cysteine (NAC),
      EUK-189, tempol and 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (CTMIO) have
      been tested for their chemopreventive properties and had some beneficial effects.
      In addition to antioxidants, cancer therapeutic agent dexamethasone was examined
      for cancer prevention in Atm deficient mice. Of the tested antioxidants, only NAC
      has wide clinical applications due to safety and efficacy and is available as an
      over-the-counter dietary supplement. In this article, we review chemoprevention
      studies in Atm deficient mice and, in more detail, our findings on the effect of
      NAC. The short-tem study showed that NAC suppressed genome rearrangements linked
      to cancer. The long-term study demonstrated that NAC reduced both the incidence
      and multiplicity of lymphoma.

PMID- 21892313
TI  - The presence of precursors of benign pre-B lymphoblasts (hematogones) in the bone
      marrow of a paediatric patient with cytomegalovirus infection.
AB  - Hematogones are normal B-lymphoid precursors that multiply in the bone marrow of
      small children and of adults with ferropenic anaemia, neuroblastoma or idiopathic
      thrombocytopenic purpura. They are not normally found in peripheral blood, and
      the immunophenotype is virtually indistinguishable from that of B lymphoblasts.
      We discuss the case of a 3-month infant with an active cytomegalovirus infection,
      with hepatitis and pancytopenia associated with 13% hematogones in the bone
      marrow.

PMID- 21892314
TI  - Multicentric Adenocarcinomas in a Long-Segment of Barrett's Esophagus.
AB  - This report describes a complicated course of a 58-year-old patient with
      multicentric Barrett's carcinoma within a long-segment of Barrett metaplasia.
      After abdominal-thoracic resection of the cancer, with incomplete removal of the
      long-segment metaplastic lesion, invasive carcinoma was diagnosed in the remnant
      Barrett's segment. Endoscopic mucosal resection was done, but Barrett's mucosa
      was left in situ again. Recurrent tumor growth was diagnosed only few months
      later. Finally, transthoracic complete resection on the remnant Barrett's segment
      was performed. Thus, our case demonstrates impressively the appearance of
      multicentric adenocarcinomas in Barrett's esophagus and underlines the necessity
      of resection of the complete Barrett mucosa.

PMID- 21892315
TI  - B-cell lymphoma of the mandible: a case report.
AB  - INTRODUCTION: The mandible is an infrequent localisation of primary osseous non
      Hodgkin's lymphomas. Few cases of mandibular non-Hodgkin's lymphomas (NHL) have
      been reported. CASE REPORT: A rare condition of primary malignant non-Hodgkin's
      lymphoma of the mandible in 53-year-old man, was reported at the Department of
      Maxillofacial and Plastic Surgery in Charles Nicolle Hospital (Tunis, Tunisia).
      Histologic and Immunohistochemical (IHC) examination Confirmed a B-Cell lymphoma.
      DISCUSSION: The purpose of this report is to describe this rare case of NHL of
      the mandible, explore the diagnosis and workup, and discuss treatment strategies.
      In this localisation, neither the clinical features nor the radiologic
      appearances are often pathognomonic. CONCLUSION: Particular care must be taken to
      consider lymphoma in the differential diagnosis because this uncommon lesion can
      pose significant diagnostic problems and is frequently misdiagnosed.

PMID- 21892316
TI  - Potential of neural stem cells for the treatment of brain tumors.
AB  - Neural stem cells (NSCs) are self-renewing multipotent cells that generate the
      main phenotypes of the nervous system, neurons, astrocytes and oligodendrocytes.
      As such they hold the promise to treat a broad range of neurological diseases and
      injuries. Neural progenitor and stem cells have been isolated and characterized
      in vitro, from adult, fetal and post-mortem tissues, providing sources of
      material for cellular therapy. However, NSCs are still elusive cells and remain
      to be unequivocally identified and characterized, limiting their potential use
      for therapy. Neural progenitor and stem cells, isolated and cultured in vitro,
      can be genetically modified and when transplanted migrate to tumor sites in the
      brain. These intrinsic properties of neural progenitor and stem cells provide
      tremendous potential to bolster the translation of NSC research to therapy. It is
      proposed to combine gene therapy and cellular therapy to treat brain cancers.
      Hence, neural progenitor and stem cells provide new opportunities for the
      treatment of brain cancers.

PMID- 21892317
TI  - A Single Institution's Experience with Bevacizumab in Combination with Cytotoxic
      Chemotherapy in Progressive Malignant Glioma.
AB  - BACKGROUND: Bevacizumab and irinotecan may represent one of the most active
      treatments in progressive malignant glioma. Limited published experience with
      bevacizumab in patients with CNS tumors raises concerns regarding toxicity,
      particularly in regards to hemorrhage and thromboembolism. METHODS: We
      retrospectively reviewed 36 patients with progressive malignant glioma after
      prior resection, chemotherapy and radiation who were treated with bevacizumab at
      our institution. Patients were evaluated for bevacizumab-related adverse events,
      time to treatment failure (TTF) and overall survival (OS). Two patients who
      progressed or died prior to completion of 4 cycles of therapy were analyzed for
      adverse events only. RESULTS: Patients were treated with bevacizumab alone (1),
      bevacizumab plus irinotecan (31), or bevacizumab plus carboplatin (4). In 34
      patients who received >4 cycles of bevacizumab, median TTF and OS were 16 and 32
      weeks, respectively. Toxicities included 1 arterial thrombosis, 4 venous
      thromboses, and 3 clinically significant CNS hemorrhages. CONCLUSION: Overall,
      our results confirm the efficacy and safety of bevacizumab in combination with
      chemotherapy in patients with progressive malignant glioma. Although the TTF and
      OS were less than previously reported with the combination of bevacizumab and
      irinotecan, this was an unselected patient population with 50% of patients having
      received >1 prior chemotherapy regimen.

PMID- 21892318
TI  - Exvivo experiments of human ovarian cancer ascites-derived exosomes presented by
      dendritic cells derived from umbilical cord blood for immunotherapy treatment.
AB  - OBJECTIVES: Exosomes, a type of membrane vesicles, released from tumor cells have
      been shown to be capable of transferring tumor antigens to dendritic cells and
      activating specific cytotoxic T-lymphocytes. Recent work has demonstrated the
      presence of high numbers of exosomes in malignant effusions. Umbilical cord blood
      (UCB) is a rich source of hematopoietic stem cells and from which a significant
      number of dendritic cells can be produced. We hypothesized that the exosomes
      released from metastatic ovarian carcinoma were able to present tumor specific
      antigen to dendritic cells derived from unrelated umbilical cord blood, then
      could stimulate resting T cells to differentiate and induce effective
      cytotoxicity. STUDY DESIGN: Exosomes were isolated by ultracentrifugation of
      malignant ascites from ovarian cancer patients (n = 10). Purified exosomes were
      further characterized by Western blot analyses and immunoelectronic microscopy.
      Dendritic cells were collected from unrelated umbilical cord blood and cultured
      in the presence of GM-CSF, IL-4 and TNF-alpha. Resting T cells were mixed with
      dentritic cells previously primed with exosomes and the cytotoxicity were
      measured by MTT method. T cells were activated by DCs presented with exosomes.
      RESULTS: 1) the exosomes isolated from the ascites were membrane vesicles of
      about 30-90nm in diameter; 2) the exosomes expressed MHC class I molecules,
      HSP70, HSP90, Her2/Neu, and Mart1; and 3)umbilical cord blood-derived DCs
      previously exosome-primed stimulated resting T cells to differentiate and produce
      effective cytotoxicity. CONCLUSIONS: These results suggested that tumor-specific
      antigens present on exosomes can be presented by DCs derived from unrelated
      umbilical cord blood to induce tumor specific cytotoxicity and this may represent
      as a novel immunotherapy for ovarian cancer.

PMID- 21892319
TI  - Documentation of complete response in metastatic breast cancer to liver and bone
      achieved with trastuzumab and pegylated liposomal Doxorubicin.

PMID- 21892320
TI  - Phase II Clinical Trial of GM-CSF Treatment in Patients with Hormone-Refractory
      or Hormone-Naive Adenocarcinoma of the Prostate.
AB  - The objective of this Phase II clinical trial was to determine the effects of
      chronic GM-CSF dosing on PSA levels in men with hormone-refractory or hormone
      naive prostate cancer. Six hormone-refractory and 10 hormone-naive patients were
      recruited from an institutional practice and were treated with 250 and 125
      MUg/m(2) of GM-CSF, respectively, 3 times per week for continuous 12-week
      treatment cycles until evidence of disease progression, as indicated by 2
      consecutive rising PSA levels. PSA levels were measured every 6 weeks. Of the 6
      hormone-refractory patients, 2 were classified with progressive disease after 4
      months and 1 after 1.75 months. The best PSA responses for the remaining 3
      patients were 3%, 12%, and 32% declines which lasted from 1.75 to 8.5 months. Of
      the 10 hormone-naive patients, 2 were classified with progressive disease after 3
      and 12 months, and 1 patient met the criteria for stable disease after 7.75
      months. The best PSA response for the remaining 7 patients ranged from 7% to 42%
      declines which lasted from 0.5 to 10 months. These results indicate that further
      study of GM-CSF administration is not warranted for hormone-refractory patients
      but is recommended for hormone-naive patients using a chronic dosing regimen.

PMID- 21892321
TI  - Case report: thymic carcinoma metastatic to small bowel.

PMID- 21892322
TI  - Recurrent Respiratory Papillomatosis (RRP)-Juvenile Onset.
AB  - In this article, we describe the treatment of long standing juvenile-onset
      recurrent respiratory papillomatosis (JORRP) with eventual transformation to
      carcinoma in a patient who lived to the age of 73. Treatment modalities consisted
      of bronchoscopy and local excision initially. Later, YAG and CO2 laser debulking
      were used. Radiotherapy, chemotherapy with carboplatin (300 mg/m2) and 5-FU (600
      mg/m2), oral methotrexate (5-7.5 mg/week), pegylated Interferon, indole-3
      carbamide, and intralesional cidofovir were also utilized in the treatment of
      this patient. Except for methotrexate, each of the treatment regimens used in
      this patient, initially decreased growth of the papillomas and improved symptoms
      experienced by the patient. Interestingly, we found that this patient's long
      standing JORRP initially responded to a chemotherapy regimen of 4 cycles of
      carboplatin (300 mg/m2) and 5-FU (600 mg/m2) as well. Ultimately, the disease
      became resistant to all forms of treatment and progressed. The patient eventually
      succumbed to the disease after an approximate 77 year course.

PMID- 21892323
TI  - Bone Marrow Micrometastases in Breast Cancer Patients: A Long-Term Follow-up
      Study.
AB  - In 125 early breast cancer patients who underwent multiple bone marrow aspirates,
      there was no significant difference in terms of disease-free and overall survival
      after a median follow-up of 163 months between the patients with or without
      micrometastasis at the time of primary surgery. However, when the time-dependent
      evolution of the bone marrow aspirates was taken into account, some evidence for
      a longer disease-free and overall survival was found for the patients with
      negative bone marrow.

PMID- 21892324
TI  - Targeted chemotherapy using a cytotoxic somatostatin conjugate to inhibit tumor
      growth and metastasis in nude mice.
AB  - The major problems of traditional chemotherapy are non-selectivity and non
      specificity, resulting in severe toxic side effects. Peptides are a new
      generation of drug-delivery vector to increase efficacy of this therapy and avoid
      the resulting damage. The cytotoxic somatostatin (SST) conjugate JF-10-81 was
      developed by coupling camptothecin (CPT) to the N-terminus of a SST analog (JF-07
      69) using an activated carbamate linker. This conjugate selectively targets
      somatostatin receptor subtype 2 (SSTR2) and also retains high binding affinity
      and rapid internalization as well as anti-proliferative activity towards various
      tumor cells. JF-10-81 was tested for its inhibitory activity against the growth
      of human tumors which included neuroblastoma (IMR32), pancreatic cancer (CFPAC
      1), leukemia (MOLT-4), pancreatic carcinoid (BON) and prostate cancer (PC-3).
      Both SSTR2 mRNAs and proteins were detected in all these tumor cell lines. The
      conjugate displayed potent in vivo inhibitory activity, although some of the
      potency measured in in vitro experiments was lost. JF-10-81 was found to
      significantly inhibit growth of these SSTR-positive tumors, resulting in 87%
      tumor reduction in neuroblastoma IMR32 and 97% in leukemia MOLT-4 bearing
      animals, even inducing regression of CFPAC-1 tumors. SSTR-overexpressing BON
      tumors were unfortunately relatively CPT-insensitive in vitro, however, JF-10-81
      again exhibited in vivo potency presumably by specifically increasing CPT
      concentrations inside the tumor cells so that the inhibition rate for JF-10-81
      was 85%. Also, JF-10-81 was used to treat highly invasive PC-3 tumors where s.c.
      injections inhibited both tumor growth (almost 60% reduction) and tumor
      metastasis (over 70%). This conjugate demonstrated its broad and excellent anti
      tumor activity by targeting SSTR2-specific tumor tissues, supporting that short
      peptides and their analogs may be applied as ideal drug-delivery carriers to
      improve the traditional chemotherapy.

PMID- 21892325
TI  - A phantom study on target localization accuracy using cone-beam computed
      tomography.
AB  - The purpose of this study is to evaluate the 3-dimensional target localization
      accuracy of cone-beam computed tomography (CBCT) using an on-board imager (OBI).
      An anthropomorphic pelvis phantom was used to simulate a range of offsets in the
      three translational directions and rotations around each of the three axes. After
      a translational or rotational offset was applied, a CBCT scan of the phantom was
      followed by image registration to detect the offsets in six degrees. The detected
      offsets were compared to the offset actually applied to give the detection error
      of the phantom position. Afterwards, the phantom was positioned by automatically
      moving the couch based on the detected offsets. A second CBCT scan followed by
      image registration was performed to give the residual error of the phantom
      positioning. On the average the detection errors and their standard deviations
      along the lateral, longitudinal and vertical axis are 0.3 +/- 0.1, 0.3 +/- 0.1
      and 0.4 +/- 0.1 mm respectively with respect to translational shifts ranging from
      0 to 10 mm. The corresponding residual errors after positioning are 0.3 +/- 0.1,
      0.5 +/- 0.1 and 0.3 +/- 0.1 mm. For simulated rotational shifts ranging from 0 to
      5 degrees, the average detection error and their standard deviation around
      lateral, longitudinal, and vertical axes are 0.1 +/- 0.0, 0.2 +/- 0.0, and 0.2 +/
      0.0 degrees respectively. The residual errors after positioning are 0.4 +/- 0.1,
      0.6 +/- 0.1, and 0.3 +/- 0.1 mm along the lateral, longitudinal and vertical
      directions. These results indicate that target localization based on CBCT is
      capable of achieving sub-millimeter accuracy.

PMID- 21892326
TI  - Serum messenger RNA as a biomarker and its clinical usefulness in malignancies.
AB  - A number of biomarkers are used clinically and many protein-based assay methods
      are available. Improvements in the method to utilize specific antibodies have led
      to remarkable progress in clinical diagnosis using biomarkers. Proteomics studies
      to identify better biomarkers have been performed worldwide by using a protein
      based comprehensive method. The detection rate of conventional biomarkers can not
      improve further. Now is a time that a breakthrough is needed. We previously
      proposed mRNA, which is circulating in the body, as a novel material for
      biomarkers. mRNA is an unexpectedly useful molecule, not only because it can
      detect genes with a low expression level in protein, but also because it can
      detect the expression from non-coding RNA precursor genes or gene products with
      limited secretion from the cells. Circulating mRNA has been thought to be
      unstable in blood containing RNase. We confirm that mRNA remains at the same
      level for 24 hours after blood sampling. Unlike DNA, the RNA molecule can reflect
      events in the human body which occurred within a day, resulting in an early
      diagnosis of diseases. We report the possibility to detect and quantify cancer
      derived mRNAs circulating in human vessels. We introduce the detection of serum
      mRNA as a useful biomarker of human malignancies.

PMID- 21892327
TI  - Adenocarcinoma Arising within a Colonic Diverticulum in a Patient with Recurrent
      Diverticulitis.
AB  - In 2006, while admitted in our hospital for surgical treatment of recurrent
      diverticulitis, a 54-year-old man was found to have an adenocarcinoma arising
      within a colonic diverticulum. Computed tomography, during this episode of
      diverticulitis, showed a thickened wall of the sigmoid and inflammatory
      induration of the pericolonic fat. Colonoscopy could be performed up to no more
      then 25 cm from the anus due to mucosal edema. A sigmoid resection was performed.
      Histopathological examination of the resected specimen showed an inflamed
      diverticulum with a submucosal adenocarcinoma of the intestinal type within its
      wall. The surrounding flat colonic mucosa was not involved by the cancerous
      process. Due to lymph node involvement the patient received adjuvant chemotherapy
      and remained disease free during follow up.

PMID- 21892328
TI  - Paclitaxel, Epirubicin and Capecitabine (TEX) as First-Line Treatment for
      Metastatic Breast Cancer: a Pilot Phase I/II Feasibility Study.
AB  - Thirteen patients with untreated metastatic breast cancer received epirubicin 60
      mg/m(2), paclitaxel 155 mg/m(2) (both day 1) and capecitabine 665 mg/m(2) twice
      daily (days 1-14) every 21 days, with intra-patient dose escalation/reduction.
      Grade 3/4 events were infrequent. Nine patients (69%) achieved an objective
      response. Median time to progression and overall survival were 6.6 and 23.5
      months, respectively.

PMID- 21892330
TI  - Increased incidence of loco-regional recurrences among african american women
      with terminal stage breast cancer.
AB  - A prospective analysis of women with terminal breast cancer admitted to CHNE from
      November 2006-August 2007 evaluated anecdotal observations that African American
      (AA) women are likelier than Caucasian women to evidence loco-regional
      recurrences (LRR). Women with terminal breast cancer who were admitted to CHNE, a
      not-for-profit hospice serving over 90% of Northeast Florida hospice patients,
      were eligible for participation. 134 terminal breast cancer patients were
      assessed by hospice nurses for LRR presence via chest wall examination. 80% of
      them (107) were Caucasian, 17% (23) were AA and 3% (4) were of other ethnicities.
      Evidence of LRR were noted in 13% of the women (17/134). The proportion of
      patients with LRR was higher in AA women than Caucasian women (26% vs. 10%, 6/23
      vs. 11/107, respectively), although this difference was not statistically
      significant (p = 0.08). The majority of Caucasian women with LRR consented to a
      medical record review, but a minority of AA women consented (8/11 vs. 2/6,
      respectively, p = 0.16). CONCLUSION: Evaluating disparities in breast cancer care
      outcomes is possible by reviewing data from patients served by hospice programs
      that aid a majority of patients within a community. This pilot data suggests that
      AA women with breast cancer have a higher incidence of loco-regional failure as a
      component of their terminal breast cancer disease than Caucasian women. A smaller
      proportion of AA patients and families agreed to participate in a medical record
      review study than Caucasians. Larger studies are necessary to confirm these
      findings, to elucidate factors contributing to disparities and to develop
      potential solutions.

PMID- 21892329
TI  - Nef as a Proliferative Factor for Kidney Epithelial Cells in HIV-Associated
      Nephropathy.

PMID- 21892331
TI  - Observational study of topical imiquimod immunotherapy in the treatment of
      difficult lentigo maligna.

PMID- 21892332
TI  - Docetaxel as salvage therapy in highly pretreated and drug resistant
      gastrointestinal carcinomas.
AB  - INTRODUCTION: Despite many efforts to develop new chemotherapies for metastatic
      upper gastrointestinal (GI) cancer, overall prognosis continues to be fatal,
      particularly in gastric and pancreatic cancer. Many of these patients deserve
      second-or third-line treatment after failure of first-line chemotherapy.
      Therefore, we analysed toxicity and response rate of weekly docetaxel after
      failed upfront regimes in these upper GI cancer patients. PATIENTS AND METHODS:
      Between 2001 and 2006, 18 patients received docetaxel based regimes (35 mg/m(2)
      weekly) after informed consent. Response rates were determined using RECIST
      criteria or tumor progression if clinically evident. Toxicities were graded based
      on NCI CTC criteria (version 2). Most patients had gastric cancer (13/18). The
      remaining entities comprised of bilio-pancreatic cancer (5/18). RESULTS:
      Docetaxel was administered as 2nd line therapy in 28% (5/18), 3rd line therapy in
      56% (10/18) and 4th or 5th line therapy in 17% (3/18). The average docetaxel dose
      was 38 mg/m(2) (Median: 35 mg/m(2)) once weekly. Over a treatment duration of
      14.7 weeks, the average dosage was 58 gr per patient and week. Overall, docetaxel
      was well tolerated with only few chemotherapy-associated toxicities (Grade 3/4),
      including nausea (17%), polyneuropathy (17%), anorexia (11%), neutropenia (6%)
      and leukopenia (17%). Docetaxel administration did not achieve any complete
      responses (CR) and one (5.6%) partial response (PR) was seen (1/18). In addition
      5 patients (27.8%) had stable disease (SD), thus inducing a tumor control rate of
      33.3% (6/18). Median progression-free survival was 2.4 months for all patients,
      2.1 months in the gastric-cancer and 2.4 months in the bilio-pancreatic cancer
      subgroups respectively. After first docetaxel administration median survival for
      all patients was 4.5 months, patients with gastric cancer survived for 4.9 months
      whereas patients suffering from bilio-pancreatic carcinoma survived for 4.2
      months. However, taken together 27% (5/18) had a remarkable overall survival of
      more than 2.5 years. DISCUSSION: In severely pretreated patients, with documented
      chemoresistant GI tumors, weekly docetaxel was well tolerated, presented good
      tumor control rate and overall survival. Therefore, this regimen may be used as
      salvage treatment in individual patients with upper GI cancers.

PMID- 21892333
TI  - Psychological Distress among Prostate Cancer Patients: Fact Or Fiction?
AB  - Although the detrimental effect upon psychological well-being of receiving a
      diagnosis of, or treatment for, cancer has been demonstrated across many
      different types of cancer, three recent reviews of the psychological health of
      prostate cancer patients have produced contradictory conclusions. In order to
      elucidate the reasons for these apparent different conclusions, each of these
      reviews is described, with principal methods and findings summarised. Actual
      data, methodology used to select/reject research studies for inclusion in
      reviews, plus the validity of strict methodological culling of some research
      studies are discussed. Several extra studies and commentaries are also described,
      and a resolution of the apparent contradictory review conclusions is offered.

PMID- 21892334
TI  - Current and emerging treatments for uterine myoma - an update.
AB  - Uterine myomas, the most common benign, solid, pelvic tumors in women, occur in
      20%-40% of women in their reproductive years and form the most common indication
      for hysterectomy. Various factors affect the choice of the best treatment
      modality for a given patient. Asymptomatic myomas may be managed by reassurance
      and careful follow up. Medical therapy should be tried as a first line of
      treatment for symptomatic myomas, while surgical treatment should be reserved
      only for appropriate indications. Hysterectomy has its place in myoma management
      in its definitiveness. However, myomectomy, rather than hysterectomy, should be
      performed when subsequent childbearing is a consideration. Preoperative
      gonadotropin-releasing hormone analog treatment before myomectomy decreases the
      size and vascularity of the myoma but may render the capsule more fibrous and
      difficult to resect. Uterine artery embolization is an effective standard
      alternative for women with large symptomatic myomas who are poor surgical risks
      or wish to avoid major surgery. Its effects on future fertility need further
      evaluation in larger studies. Serial follow-up without surgery for growth and/or
      development of symptoms is advisable for asymptomatic women, particularly those
      approaching menopause. The present article is incorporated with multiple clear
      clinical photographs and simplified elaboration of the available management
      options for these tumors of uterine smooth muscle to facilitate clear
      understanding.

PMID- 21892335
TI  - The role of corifollitropin alfa in controlled ovarian stimulation for IVF in
      combination with GnRH antagonist.
AB  - Corifollitropin alfa is a synthetic recombinant follicle-stimulating hormone
      (rFSH) molecule containing a hybrid beta subunit, which provides a plasma half
      life of ~65 hours while maintaining its pharmocodynamic activity. A single
      injection of corifollitropin alfa can replace daily FSH injections for the first
      week of ovarian stimulation for in vitro fertilization. Stimulation can be
      continued with daily FSH injections if the need arises. To date, more than 2500
      anticipated normoresponder women have participated in clinical trials with
      corifollitropin alfa. It is noteworthy that one-third of women did not require
      additional gonadotropin injections and reached human chorionic gonadotropin
      criterion on day 8. The optimal corifollitropin dose has been calculated to be
      100 MUg for women with a body weight <=60 kg and 150 MUg for women with a body
      weight >60 kg, respectively. Combination of corifollitropin with daily
      gonadotropin-releasing hormone antagonist injections starting on stimulation day
      5 seems to yield similar or significantly higher numbers of oocytes and good
      quality embryos, as well as similar ongoing pregnancy rates compared with women
      stimulated with daily rFSH injections. Stimulation characteristics, embryology,
      and clinical outcomes seem consistent with repeated corifollitropin-stimulated
      assisted reproductive technologies cycles. Multiple pregnancy or ovarian
      hyperstimulation syndrome rates with corifollitropin were not increased over
      daily FSH regimen. The corifollitropin alfa molecule does not seem to be
      immunogenic and does not induce neutralizing antibody formation. Drug
      hypersensitivity and injection-site reactions are not increased. Incidence and
      nature of adverse events and serious adverse events are similar to daily FSH
      injections. Current trials do not provide information regarding use of
      corifollitropin alfa in anticipated hyper- and poor responders to gonadotropin
      stimulation. Although corifollitropin alfa is unlikely to be teratogenic, at the
      moment data on congenital malformations is missing.

PMID- 21892336
TI  - The relationship of psychosocial factors to mammograms, physical activity, and
      fruit and vegetable consumption among sisters of breast cancer patients.
AB  - This study examined the relationship of psychosocial factors to health-promoting
      behaviors in sisters of breast cancer patients. One hundred and twenty sisters of
      breast cancer patients completed questionnaires assessing response efficacy of
      mammography screenings, physical activity, and fruit and vegetable consumption on
      decreasing breast cancer risk, breast cancer worry, involvement in their sister's
      cancer care, mammography screenings, physical activity, and fruit and vegetable
      consumption. Results indicate that greater perceived effectiveness for mammograms
      was associated with a 67% increase in odds of yearly mammograms. Greater
      involvement in the patient's care was associated with a 7% decrease in odds of
      yearly mammograms. Greater perceived effectiveness for physical activity was
      significantly related to greater physical activity. There was a trend for greater
      perceived effectiveness for fruits and vegetables to be associated with consuming
      more fruits and vegetables. Breast cancer worry was not significantly associated
      with the outcomes. While perceived effectiveness for a specific health behavior
      in reducing breast cancer risk was consistently related to engaging in that
      health behavior, women reported significantly lower perceived effectiveness for
      physical activity and fruits and vegetables than for mammograms. Making women
      aware of the health benefits of these behaviors may be important in promoting
      changes.

PMID- 21892337
TI  - A review of management of infertility in Nigeria: framing the ethics of a
      national health policy.
AB  - Infertility has recently been construed to be a serious problem in sub-Saharan
      Africa. This problem seems to be viewed as of low priority with reference to the
      effective and efficient allocation of available health resources by national
      governments as well as by international donors sponsoring either research or
      service delivery in the public health sector. In this paper the problem of
      infertility in Nigeria is surveyed with a view to assessing the ethical dimension
      of proposals to manage infertility as a public sector priority in health care
      delivery. The population/individual and public/private distinction in the
      formulation of health policy has ethical implications that cannot simply be
      ignored and are therefore engaged in critically assessing the problem of
      infertility. Cost-utility analysis (such as Quality Adjusted Life-Year composite
      index) in the management of infertility in Nigeria entails the need for caution
      relevant to the country's efforts to achieve Millennium Development Goals. This
      should remain the case whether the ethical evaluation appeals to utilitarian or
      contractarian (Rawlsian) principles. The "worst off " category of Nigerians
      includes (1) underweight children less than 5 years of age, with special concern
      for infants (0-1 years of age) and (2) the proportion of the population below a
      minimum level of dietary consumption. The Rawlsian ethic implies that any Federal
      Ministry of Health policy aimed at establishing public programs for infertility
      management can be considered a "fair" allocation and expenditure if, and only if,
      the situation for these two cohorts is not thereby made worse. Nigerian health
      policy cannot assume this type of increased allocation of its resources to
      infertility care without it being hard pressed to warrant defensible moral or
      rational argument.

PMID- 21892338
TI  - Transvaginal ultrasonography compared with Bishop score for predicting cesarean
      section after induction of labor.
AB  - BACKGROUND: Reproductive health researchers are interested in finding better
      methods for predicting an unwanted type of delivery after induction of labor. The
      aim of this study was to compare the value of transvaginal ultrasonography
      findings and the Bishop score in predicting cesarean section after induction of
      labor. METHODS: Two hundred women with singleton pregnancies undergoing induction
      of labor at 37-42 weeks were enrolled in this prospective study. Transvaginal
      investigation was done for all participants prior to induction. To compare the
      predictive value of the methods, receiver-operating characteristic (ROC) curves
      were plotted and equality of the area under curve (AUC) was tested. RESULTS: The
      mean age of the participants was 29.9 years, mean gestational age was 39.6 weeks,
      and mean gravid was 1.5. The AUC calculated for Bishop score was 0.39 (95%
      confidence interval [CI] 0.3-0.48). The AUC for cervical length measured by
      ultrasonography was 0.69 (95% CI 0.6-0.77). The AUC for the posterior cervical
      angle measured by ultrasonography was 0.38 (95% CI 0.29-0.47). Testing equality
      of the ROC curves for these three methods showed the ROC for cervical length to
      be statistically different from both Bishop score and posterior cervical angle (P
      < 0.001). However, the difference in ROC area compared between Bishop score and
      posterior cervical angle was not statistically significant. CONCLUSION: Based on
      our findings and available information in the literature, it seems that cervical
      length measured by transvaginal ultrasonography has the potential to replace the
      traditional Bishop score, provided that such a facility is available when needed.

PMID- 21892339
TI  - Estradiol valerate and dienogest: a new approach to oral contraception.
AB  - Most combination oral contraceptives contain ethinyl estradiol and a progestin. A
      new and novel oral contraceptive formulation combines estradiol valerate (E2V)
      with dienogest (DNG) in a four-phase dosing regimen. 17beta-estradiol is a
      naturally-occurring estrogen, and a contraceptive pill containing such an
      estrogen offers potential benefits with regard to metabolic side effects and
      adverse events. Dienogest is derived from 19-nortestosterone and exerts profound
      progestational effects on the endometrium, but it differs from other progestins
      in its class by its antiandrogenic activity. Estradiol valerate plus dienogest
      (E2V/DNG) is now available in a four-phasic regimen that integrates an estrogen
      stepdown and progestin stepup dosing approach along with a short two-day hormone
      free interval. This regimen offers safe, reliable contraception and has been
      shown to be an effective treatment for heavy menstrual bleeding. Metabolic
      effects and adverse events appear similar to those reported with oral
      contraceptives containing ethinyl estradiol.

PMID- 21892341
TI  - Similarities Among the Shapes of Writing and Their Effects on Learning.
AB  - Writing systems are usually studied in terms of the level of language that they
      represent, with little attention to the shapes that are used to do so. Those
      shapes are not random or accidental, however. They tend to be similar to one
      another within a script. Many of the Latin letters have a roughly vertical stem
      or hasta with an appendage or coda to the right. This arrangement is more common
      than one with the coda on the left of the hasta. We present data to show that
      young children are generally better at copying and writing from memory shapes
      such as <b> and <F>, which have the typical arrangement with the coda on the
      right, than those such as <d> and <J>, which do not. The results suggest that
      children start to learn about the statistics of the letter shapes before they
      know how or that these shapes represent language.

PMID- 21892340
TI  - Randomized clinical trial evaluating the frequency of membrane sweeping with an
      unfavorable cervix at 39 weeks.
AB  - BACKGROUND: Despite the widely accepted use of membrane sweeping to prevent
      postmaturity pregnancies, the optimal frequency for this procedure has not been
      established. AIM: To determine if the frequency of membrane sweeping in women
      with an unfavorable cervix at term results in fewer labor inductions. METHODS:
      This was a randomized trial of women with an unfavorable cervix (Bishop's score
      of <=4) at 39 weeks randomized into three groups: control, once-weekly membrane
      sweeping, and twice-weekly membrane sweeping. RESULTS: Between January 2005 and
      June 2008, 350 women were randomized into the study (groups: control [n = 116],
      once weekly [n = 117], and twice weekly [n = 117]). Randomization of Bishop's
      score was different between groups (P = 0.019), with 67%, 71%, and 83% of
      control, once-, and twice-weekly groups, respectively, having scores of 3-4.
      There was no difference in the unadjusted rate of labor induction between the
      groups (35% versus 27% versus 23%, P = 0.149), and after the adjustment for the
      randomization of Bishop's score (adjusted odds ratio [OR] = 0.73, 95% confidence
      interval [CI] 0.41-1.29 and OR = 0.65, 95% CI 0.36-1.18 for once- and twice
      weekly groups, respectively). A Bishop's score of 3-4 at randomization was the
      only statistically significant factor that decreased the likelihood of induction
      at 41 weeks (OR = 0.42, 95% CI 0.25-0.69). CONCLUSION: Frequency of membrane
      sweeping does not influence the likelihood of remaining undelivered at 41 weeks
      of pregnancy. The Bishop's score at around 39 weeks is the important factor as a
      predictor of the duration of pregnancy, and further studies would be required to
      determine whether membrane sweeping influences pregnancy duration.

PMID- 21892342
TI  - Differentially Private Empirical Risk Minimization.
AB  - Privacy-preserving machine learning algorithms are crucial for the increasingly
      common setting in which personal data, such as medical or financial records, are
      analyzed. We provide general techniques to produce privacy-preserving
      approximations of classifiers learned via (regularized) empirical risk
      minimization (ERM). These algorithms are private under the epsilon-differential
      privacy definition due to Dwork et al. (2006). First we apply the output
      perturbation ideas of Dwork et al. (2006), to ERM classification. Then we propose
      a new method, objective perturbation, for privacy-preserving machine learning
      algorithm design. This method entails perturbing the objective function before
      optimizing over classifiers. If the loss and regularizer satisfy certain
      convexity and differentiability criteria, we prove theoretical results showing
      that our algorithms preserve privacy, and provide generalization bounds for
      linear and nonlinear kernels. We further present a privacy-preserving technique
      for tuning the parameters in general machine learning algorithms, thereby
      providing end-to-end privacy guarantees for the training process. We apply these
      results to produce privacy-preserving analogues of regularized logistic
      regression and support vector machines. We obtain encouraging results from
      evaluating their performance on real demographic and benchmark data sets. Our
      results show that both theoretically and empirically, objective perturbation is
      superior to the previous state-of-the-art, output perturbation, in managing the
      inherent tradeoff between privacy and learning performance.

PMID- 21892343
TI  - Nurse empowerment from a middle-management perspective: nurse managers' and
      assistant nurse managers' workplace empowerment views.
AB  - BACKGROUND: Researchers have explored empowerment as an important condition for
      nursing staff but little current research focuses on empowerment from a middle
      management perspective. AIMS AND OBJECTIVES: The purpose of this study was to
      assess the empowerment of a middle-management group made up of only nurse
      managers (NMs) and assistant nurse managers (ANMs) in an acute-care hospital
      setting. METHODS: A questionnaire was distributed online to a convenience sample
      of NMs (n = 11) and ANMs (n = 31) working in an ethnically diverse acute-care
      hospital. RESULTS: Overall, this middle-management group did not feel empowered.
      CONCLUSIONS: Empowerment as perceived by middle management is crucial for
      carrying out leadership duties and, in turn, empowering frontline staff. Even
      though the work is challenging, resources and support, among other constructs of
      empowerment, must be improved to increase the empowerment of middle management.
      Nursing administration must understand the importance of an empowered middle
      management so that middle management can lead effectively and facilitate the
      delivery of safe, high-quality patient care.

PMID- 21892344
TI  - Maintaining optimal oxygen saturation in premature infants.
AB  - INTRODUCTION: Advances in technology have resulted in increasing survival rates
      for premature infants. Oxygen therapy is commonly used in neonatal units as part
      of respiratory support. The number of premature infants in our institution
      surviving with severe (stage >=3) retinopathy of prematurity (ROP) prompted a
      review of oxygen therapy as a contributing factor. Prolonged exposure to high
      concentrations of oxygen may cause irreversible damage to the eyes of very-low
      birth-weight preterm infants and is a potential cause of blindness. OBJECTIVE: We
      developed strategies to reduce incidence of severe ROP requiring laser surgery in
      premature infants. METHODS: We studied 37 preterm infants who were born at a
      gestational age of <32 weeks, with a birth weight of <1500 g, receiving
      supplemental oxygen, and had been admitted to our neonatal intensive care unit.
      Infants received oxygen via mechanical ventilator, nasal continuous positive
      airway pressure (CPAP), or intranasal (I/N) and titration of oxygen was based on
      each infant's measured oxygen saturation (Spo(2)). For each infant, we monitored
      the Spo(2) trend, Spo(2) alarm limit, and the percentage of time that the alarm
      limit was set incorrectly. We implemented a Spo(2) targeting protocol and
      developed an algorithm for titrating fraction of inspired oxygen (Fio(2)).
      RESULTS: After phase 1 of implementation, the percentage of time that Spo(2)
      readings were >95% was reduced to between 20% and 50%. However, our findings
      raised concern regarding the wide fluctuation of Spo(2) readings because of
      inconsistency in Fio(2) titration, which can contribute to deviation from the
      optimal target range. Accordingly, we developed an algorithm for titrating Fio(2)
      aimed at maintaining each infant's Spo(2) within the optimal target range. After
      phase 2 of implementation, the percentage of Spo(2) readings >95% was markedly
      reduced to between 0% and 15%. The incidence of infants with severe ROP requiring
      laser surgery decreased from 5 to 1. CONCLUSIONS: A change in clinical practice
      aimed at maintaining oxygen within the target range to avoid a high Spo(2) was
      associated with a significant decrease in the incidence of both severe ROP and
      the need for laser surgery, thus reducing hospital costs and length of hospital
      stays for premature infants.

PMID- 21892345
TI  - Neglected Food Bubbles: The Espresso Coffee Foam.
AB  - Coffee beverage known as espresso, must be topped by a velvety thick, reddish
      brown foam called crema, to be considered properly prepared and to be appreciated
      by connoisseurs. In spite of the relevant role played by crema as a quality
      marker, espresso coffee foam has not yet been the subject of detailed
      investigations. Only recently, some aspects of the Physics and Chemistry behind
      the espresso coffee foam have attracted the attention of scientists. In addition
      to sharing several characteristics with other food foams like beer foam, for
      instance, the espresso coffee foam may contain solid particles (minute coffee
      cell-wall fragments), it is subjected to a remarkable temperature gradient and
      its continuous phase is an oil in water emulsion rendering it a very complex
      system to be studied. Moreover, in the typical regular espresso coffee cup volume
      (serving) of 25-30 mL, crema represents at least 10% of the total volume, and
      this is a limitation in obtaining experimental data by conventional instruments.
      The present work is aimed at reviewing the literature on espresso coffee foam.
      The traditional espresso brewing method will be briefly described with emphasis
      on the steps particularly relevant to foam formation and stabilization. In
      addition to present up-dated experimental data on surface properties at
      solid/beverage and air/beverage interface, recent advances on the espresso foam
      formation mechanism, as well as on foam stability, will be critically examined.
      The key role played by carbon dioxide generated by roasting and the effects of
      low and high-molecular-weight coffee compounds in promoting/inhibiting the
      espresso coffee foam will be discussed and emphasized.

PMID- 21892346
TI  - New cembranolides from the Dongsha Atoll soft coral Lobophytum durum.
AB  - Chemical investigations of the Dongsha Atoll soft coral Lobophytum durum resulted
      in the isolation of five new cembranolides, durumolides M-Q (1-5). The structures
      of compounds 1-5 were characterized by the interpretation of extensive
      spectroscopic analysis. Compound 4 exhibited cytotoxicity against P-388 (mouse
      lymphocytic leukemia) cell line with an ED50 of 3.8 MUg/mL. Moreover, compound 5
      showed significant antiviral activity against human cytomegalovirus with an IC50
      of 5.2 MUg/mL.

PMID- 21892347
TI  - Lobocrassins A-E: new cembrane-type diterpenoids from the soft coral Lobophytum
      crassum.
AB  - Five new cembrane-type diterpenoids, lobocrassins A-E (1-5), were isolated from
      the soft coral Lobophytum crassum. The structures of cembranes 1-5 were
      established by spectroscopic and chemical methods and by comparison of the
      spectral data with those of known cembrane analogues. Lobocrassin A (1) is the
      first cembranoid possessing an alpha-chloromethyl-alpha-hydroxy-gamma-lactone
      functionality and is the first chlorinated cembranoid from soft corals belonging
      to the genus Lobophytum. Lobocrassins B (2) and C (3) were found to be the
      stereoisomers of the known cembranes, 14-deoxycrassin (6) and pseudoplexaurol
      (7), respectively. Lobocrassin B (2) exhibited modest cytotoxicity toward K562,
      CCRF-CEM, Molt4, and HepG2 tumor cells and displayed significant inhibitory
      effects on the generation of superoxide anion and the release of elastase by
      human neutrophils.

PMID- 21892349
TI  - Evaluation of marine brown algae and sponges from Brazil as anticoagulant and
      antiplatelet products.
AB  - The ischemic disorders, in which platelet aggregation and blood coagulation are
      involved, represent a major cause of disability and death worldwide. The
      antithrombotic therapy has unsatisfactory performance and may produce side
      effects. So, there is a need to seek molecules with antithrombotic properties.
      Marine organisms produce substances with different well defined ecological
      functions. Moreover, some of these molecules also exhibit pharmacological
      properties such as antiviral, anticancer, antiophidic and anticoagulant
      properties. The aim of this study was to evaluate, through in vitro tests, the
      effect of two extracts of brown algae and ten marine sponges from Brazil on
      platelet aggregation and blood coagulation. Our results revealed that most of the
      extracts were capable of inhibiting platelet aggregation and clotting measured by
      plasma recalcification tests, prothrombin time, activated partial thromboplastin
      time, and fibrinogenolytic activity. On the other hand, five of ten species of
      sponges induced platelet aggregation. Thus, the marine organisms studied here may
      have molecules with antithrombotic properties, presenting biotechnological
      potential to antithrombotic therapy. Further chemical investigation should be
      conducted on the active species to discover useful molecules for the development
      of new drugs to treat clotting disorders.

PMID- 21892348
TI  - Aqueous and methanolic extracts of Caulerpa mexicana suppress cell migration and
      ear edema induced by inflammatory agents.
AB  - The regulation of the inflammatory response is essential to maintaining
      homeostasis. Several studies have investigated new drugs that may contribute to
      avoiding or minimizing excessive inflammatory process. The aim of this study was
      to evaluate the effect of extracts of green algae Caulerpa mexicana on models
      inflammation. In mice, the inflammatory peritonitis model is induced by zymosan.
      Previous treatment of mice with aqueous and methanolic extracts of C. mexicana
      was able to suppress the cell migration to the peritoneal cavity, in a time
      dependent but not in a dose-dependent manner. The treatment of mice with C.
      mexicana extracts also decreased the xylene-induced ear edema, exerting strong
      inhibitory leukocyte migration elicited by zymosan into the air pouch. We
      concluded that administration of the extracts resulted in a reduction of cell
      migration to different sites as well as a decrease in edema formation induced by
      chemical irritants. This study demonstrates for the first time the anti
      inflammatory effect of aqueous and methanolic extracts from the green marine
      algae Caulerpa mexicana.

PMID- 21892350
TI  - Fucoidan from marine brown algae inhibits lipid accumulation.
AB  - In this study, we elucidated the inhibitory effect of fucoidan from marine brown
      algae on the lipid accumulation in differentiated 3T3-L1 adipocytes and its
      mechanism. The treatment of fucoidan in a dose-dependent manner was examined on
      lipid inhibition in 3T3-L1 cells by using Oil Red O staining. Fucoidan showed
      high lipid inhibition activity at 200 MUg/mL concentration (P < 0.001). Lipolytic
      activity in adipocytes is highly dependent on hormone sensitive lipase (HSL),
      which is one of the most important targets of lipolytic regulation. Here, we
      examined the biological response of fucoidan on the protein level of lipolysis
      pathway. The expressed protein levels of total hormone sensitive lipase (HSL) and
      its activated form, phosphorylated-HSL were significantly increased at
      concentration of 200 MUg/mL fucoidan. Furthermore, insulin-induced 2-deoxy-D-[3H]
      glucose uptake was decreased up to 51% in fucoidan-treated cells as compared to
      control. Since increase of HSL and p-HSL expression and decrease of glucose
      uptake into adipocytes are known to lead to stimulation of lipolysis, our results
      suggest that fucoidan reduces lipid accumulation by stimulating lipolysis.
      Therefore, these results suggest that fucoidan can be useful for the prevention
      or treatment of obesity due to its stimulatory lipolysis.

PMID- 21892351
TI  - Three new compounds from Aspergillus terreus PT06-2 grown in a high salt medium.
AB  - To investigate the structurally novel and bioactive natural compounds from marine
      derived microorganisms under high salinity, the fungus Aspergillus terreus PT06-2
      was isolated from the sediment of the Putian Sea Saltern, Fujian, China. Three
      new compounds, terremides A (1) and B (2) and terrelactone A (3), along with
      twelve known compounds (4-15) were isolated and identified from the fermentation
      broth of A. terreus PT06-2 at 10% salinity. Among these metabolites, compounds 4
      and 15 only produced in the 10% salinity culture, were identified as methyl 3,4,5
      trimethoxy-2-(2-(nicotinamido) benzamido) benzoate, and (+)-terrein,
      respectively. The new compounds 1 and 2 exhibited antibacterial activity against
      Pseudomonas aeruginosa and Enterobacter aerogenes with MIC values of 63.9 and
      33.5 MUM, respectively. Compounds 5 showed moderate anti-H1N1 activity and lower
      cytotoxicity with IC50 and CC50 values of and 143.1 and 976.4 MUM, respectively.

PMID- 21892352
TI  - Diversity and antibacterial activities of fungi derived from the Gorgonian
      Echinogorgia rebekka from the South China Sea.
AB  - The diversity of symbiotic fungi associated with the gorgonian coral Echinogorgia
      rebekka from the Weizhou coral reef in the South China Sea was investigated.
      Combined with morphologic traits, ITS-rDNA sequences revealed 18 fungal strains
      from this gorgonian. All of the 18 fungi belonged to the phylum Ascomycota and
      were distributed among seven genera in five orders: Eurotiales (Aspergillus and
      Penicillium), Pleosporales (Alternaria), Capnodiales (Cladosporium),
      Trichosphaeriales (Nigrospora) and Hypocreales (Hypocrea and Nectria).
      Antibacterial activities of these fungal strains were investigated with five
      pathogenic bacteria. All of the 18 fungal strains displayed different levels of
      antibacterial activities, most of which exhibited moderate to high antibacterial
      activities to the Gram-positive pathogens Staphylococcus aureus and Micrococcus
      tetragenus, and showed relatively low bioactivities to other three pathogenic
      bacteria. Several fungal strains in the genera Penicillium and Cladosporium with
      strong antibacterial activities provide potential for further research on
      isolation of bioactive secondary metabolites.

PMID- 21892353
TI  - Identification of the antibacterial compound produced by the marine epiphytic
      bacterium Pseudovibrio sp. D323 and related sponge-associated bacteria.
AB  - Surface-associated marine bacteria often produce secondary metabolites with
      antagonistic activities. In this study, tropodithietic acid (TDA) was identified
      to be responsible for the antibacterial activity of the marine epiphytic
      bacterium Pseudovibrio sp. D323 and related strains. Phenol was also produced by
      these bacteria but was not directly related to the antibacterial activity. TDA
      was shown to effectively inhibit a range of marine bacteria from various
      phylogenetic groups. However TDA-producers themselves were resistant and are
      likely to possess resistance mechanism preventing autoinhibition. We propose that
      TDA in isolate D323 and related eukaryote-associated bacteria plays a role in
      defending the host organism against unwanted microbial colonisation and,
      possibly, bacterial pathogens.

PMID- 21892354
TI  - Bioactive (3Z,5E)-11,20-epoxybriara-3,5-dien-7,18-olide diterpenoids from the
      South China Sea gorgonian Dichotella gemmacea.
AB  - Six new (3Z,5E)-11,20-epoxybriara-3,5-dien-7,18-olide diterpenoids, gemmacolides
      N-S (1-6), were isolated together with four known analogues, juncenolide D, and
      juncins R, S and U (7-10), from the South China Sea gorgonian Dichotella
      gemmacea. The structures of the new compounds were elucidated by the detailed
      analysis of spectroscopic data in combination with the comparison with reported
      data. The absolute configuration of 1 was determined by a TDDFT calculation of
      its solution ECD spectrum, affording the determination of absolute configuration
      of other analogues by simply comparing their ECD spectra with that of 1. The
      cytotoxic and antimicrobial activities of these compounds were evaluated. In
      preliminary in vitro bioassays, compounds 4, 5, 6, 8 and 9 showed cytotoxicity
      against A549 and MG63, while compounds 1, 2, 4, 7-10 showed antimicrobial
      activity against the fungus Septoria tritici and the bacterium Escherichia coli.

PMID- 21892355
TI  - Carotenoids in marine invertebrates living along the Kuroshio current coast.
AB  - Carotenoids of the corals Acropora japonica, A. secale, and A. hyacinthus, the
      tridacnid clam Tridacna squamosa, the crown-of-thorns starfish Acanthaster
      planci, and the small sea snail Drupella fragum were investigated. The corals and
      the tridacnid clam are filter feeders and are associated with symbiotic
      zooxanthellae. Peridinin and pyrrhoxanthin, which originated from symbiotic
      zooxanthellae, were found to be major carotenoids in corals and the tridacnid
      clam. The crown-of-thorns starfish and the sea snail D. fragum are carnivorous
      and mainly feed on corals. Peridinin-3-acyl esters were major carotenoids in the
      sea snail D. fragum. On the other hand, ketocarotenoids such as 7,8
      didehydroastaxanthin and astaxanthin were major carotenoids in the crown-of
      thorns starfish. Carotenoids found in these marine animals closely reflected not
      only their metabolism but also their food chains.

PMID- 21892357
TI  - Survival and growth of seedlings of 19 native tree and shrub species planted in
      degraded forest as part of a forest restoration project in Madagascar's
      highlands.
AB  - Percentage survival and mean percentage change in height were compared for 19
      native tree and shrub species planted at Ankafobe Forest, a degraded fragment of
      highland forest, at ten months after planting. The species varied considerably in
      both, survival and growth. Best performers included Macaranga alnifolia
      (Euphorbiaceae), Harungana madagascariensis (Clusiaceae), Filicium decipiens
      (Sapindaceae) and Dodonaea madagascariensis (Sapindaceae). A comparison of
      survival between relatively short seedlings compared to relatively tall seedlings
      revealed no significant difference. This information will be used to increase the
      efficiency of forest restoration at this site.

PMID- 21892356
TI  - Pseudonocardians A-C, new diazaanthraquinone derivatives from a deap-sea
      actinomycete Pseudonocardia sp. SCSIO 01299.
AB  - Pseudonocardians A-C (2-4), three new diazaanthraquinone derivatives, along with
      a previously synthesized compound deoxynyboquinone (1), were produced by the
      strain SCSIO 01299, a marine actinomycete member of the genus Pseudonocardia,
      isolated from deep-sea sediment of the South China Sea. The structures of
      compounds 1-4 were determined by mass spectrometry and NMR experiments (1H, 13C,
      HSQC, and HMBC). The structure of compound 1, which was obtained for the first
      time from a natural source, was confirmed by X-ray analysis. Compounds 1-3
      exhibited potent cytotoxic activities against three tumor cell lines of SF-268,
      MCF-7 and NCI-H460 with IC50 values between 0.01 and 0.21 MUm, and also showed
      antibacterial activities on Staphylococcus aureus ATCC 29213, Enterococcus
      faecalis ATCC 29212 and Bacillus thuringensis SCSIO BT01, with MIC values of 1-4
      MUg mL-1.

PMID- 21892358
TI  - Comparing different scientific approaches to personalized medicine: research
      ethics and privacy protection.
AB  - In this article, two different scientific approaches to personalized medicine are
      compared. Biorepository at Vanderbilt University (BioVU) is a genomic
      biorepository at Vanderbilt University Medical Center in Nashville, TN, USA.
      Genetic biosamples are collected from leftover clinical blood samples; medical
      information is derived from an electronic medical records. Greifswald Approach to
      Individualized Medicine is a research resource at the University of Greifswald,
      Germany, comprised of clinical records combined with biosamples collected for
      research. We demonstrate that although both approaches are based on the
      collection of clinical data and biosamples, different legal milieus present in
      the USA and Germany as well as slight differences in scientific goals have led to
      different 'ethical designs'. While BioVU can successfully operate with an 'opt
      out' mechanism, an informed consent-based 'opt-in' model is indispensable to
      allow GANI_MED to reach its scientific goals.

PMID- 21892359
TI  - Early Language Learning and Literacy: Neuroscience Implications for Education.
AB  - The last decade has produced an explosion in neuroscience research examining
      young children's early processing of language that has implications for
      education. Noninvasive, safe functional brain measurements have now been proven
      feasible for use with children starting at birth. In the arena of language, the
      neural signatures of learning can be documented at a remarkably early point in
      development, and these early measures predict performance in children's language
      and pre-reading abilities in the second, third, and fifth year of life, a finding
      with theoretical and educational import. There is evidence that children's early
      mastery of language requires learning in a social context, and this finding also
      has important implications for education. Evidence relating socio-economic status
      (SES) to brain function for language suggests that SES should be considered a
      proxy for the opportunity to learn and that the complexity of language input is a
      significant factor in developing brain areas related to language. The data
      indicate that the opportunity to learn from complex stimuli and events are vital
      early in life, and that success in school begins in infancy.

PMID- 21892360
TI  - Developing Mechanisms of Self-Regulation in Early Life.
AB  - Children show increasing control of emotions and behavior during their early
      years. Our studies suggest a shift in control from the brain's orienting network
      in infancy to the executive network by the age of 3-4 years. Our longitudinal
      study indicates that orienting influences both positive and negative affect, as
      measured by parent report in infancy. At 3-4 years of age, the dominant control
      of affect rests in a frontal brain network that involves the anterior cingulate
      gyrus. Connectivity of brain structures also changes from infancy to toddlerhood.
      Early connectivity of parietal and frontal areas is important in orienting; later
      connectivity involves midfrontal and anterior cingulate areas related to
      executive attention and self-regulation.

PMID- 21892361
TI  - Assessment of Transport Mechanisms Underlying the Bicoid Morphogen Gradient.
AB  - Morphogen gradients dictate the spatial patterning of multicellular organisms and
      are established via transport mechanisms. One of the best-characterized
      morphogens, Bicoid, acts as a polarity determinant in the Drosophila embryo
      through spatial-temporal control of gap gene expression. The prevailing model for
      establishment of the gradient has been localized anterior translation, subsequent
      diffusion, and spatially uniform degradation, consistent with the observed
      exponential anterior-posterior decay. However, a recent direct measurement of the
      Bicoid diffusion coefficient via fluorescence recovery after photobleaching
      (FRAP) resulted in a surprisingly low estimate, which challenged the prevailing
      model and led to more complicated active transport models. Here, we reassessed
      this conclusion using a detailed computational model of the FRAP experiment and
      analysis. In our model, we found disagreement between the input diffusion
      coefficient and the resulting estimated diffusion coefficient, as measured by
      previous methods. By using the model to reproduce the original data, we estimate
      that Bicoid's mitotic diffusion coefficient is 3-fold larger than the originally
      reported value. Thus, the long-standing diffusive transport model still holds.

PMID- 21892362
TI  - The proof for new oral anticoagulants: clinical trial evidence.
AB  - INTRODUCTION: Patients undergoing elective total hip or total knee replacement
      surgery are at increased risk of venous thromboembolism in the post-operative
      period and are recommended to receive thromboprophylaxis for 10-35 days. Although
      several thromboprophylactic agents are available, these are associated with well
      recognized limitations. For the low molecular weight heparins (LMWHs) such as
      enoxaparin, these limitations include parenteral administration, indirect mode of
      action, inability to inhibit clot-bound thrombin and association with
      complications such as heparin-induced thrombocytopenia. These limitations make
      post-operative thromboprophylaxis challenging. Several new oral anticoagulants
      are in the advanced stages of clinical development. These agents have been
      designed to target either thrombin (dabigatran etexilate) or factor Xa
      (rivaroxaban and apixaban), which are key coagulation cascade enzymes. METHODS
      AND RESULTS: This review will present the published phase III clinical trial
      evidence of the efficacy and safety of dabigatran etexilate, rivaroxaban and
      apixaban, compared with the LMWH enoxaparin for the prevention of venous
      thromboembolism in patients who have undergone elective total hip or total knee
      replacement surgery. All three agents have shown comparable or superior efficacy
      compared with the European dose regimen of enoxaparin (40 mg once daily), and
      comparable rates of major bleeding events. Dabigatran etexilate and rivaroxaban
      are currently licensed for use following elective hip and knee replacement
      surgery in many countries, but no direct comparative data exist upon which to
      base the choice of agent. CONCLUSION: A thorough assessment of each individual
      patient's thromboembolic and bleeding risks should be the basis of selecting the
      agent in order to balance efficacy and safety.

PMID- 21892363
TI  - Innovations in total knee replacement: new trends in operative treatment and
      changes in peri-operative management.
AB  - The human knee joint can sustain damage due to injury, or more usually
      osteoarthritis, to one, two or all three of the knee compartments: the medial
      femorotibial, the lateral femorotibial and the patellofemoral compartments. When
      pain associated with this damage is unmanageable using nonsurgical techniques,
      knee replacement surgery might be the most appropriate course of action. This
      procedure aims to restore a pain-free, fully functional and durable knee joint.
      Total knee replacement is a well-established treatment modality, and more
      recently, partial knee replacement-more commonly known as bi- or unicompartmental
      knee replacement-has seen resurgence in interest and popularity. Combined with
      the use of minimally invasive surgery (MIS) techniques, gender-specific
      prosthetics and computer-assisted navigation systems, orthopaedic surgeons are
      now able to offer patients knee replacement procedures that are associated with
      (1) minimal risks during and after surgery by avoiding fat embolism, reducing
      blood loss and minimising soft tissue disruption; (2) smaller incisions; (3)
      faster and less painful rehabilitation; (4) reduced hospital stay and faster
      return to normal activities of daily living; (5) an improved range of motion; (6)
      less requirement for analgesics; and (7) a durable, well-aligned, highly
      functional knee. With the ongoing advancements in surgical technique, medical
      technology and prosthesis design, knee replacement surgery is constantly
      evolving. This review provides a personal account of the recent innovations that
      have been made, with a particular emphasis on the potential use of MIS techniques
      combined with computer-assisted navigation systems to treat younger, more
      physically active patients with resurfacing partial/total implant knee
      arthroplasty.

PMID- 21892364
TI  - Prolonged exposure to isoflurane ameliorates infarction severity in the rat pup
      model of neonatal hypoxia-ischemia.
AB  - The neonatal hypoxia-ischemia rat model referred to as the Rice-Vannucci model is
      extensively used to study perinatal hypoxia-ischemia and child brain injury. One
      of the major weaknesses of this model is its inconsistency of brain infarction
      among animals. We hypothesize that the inconsistency of infarction is caused by
      prolonged operation time and therefore isoflurane exposure. Neonatal hypoxia
      ischemia was induced in postnatal days 7 and 10 rat pups by unilateral right
      common carotid ligation followed by 2.5 h of hypoxia (8% oxygen). The incision-to
      ligation (ITL) was defined as the amount of time from initial incision (4 min
      after 2% isoflurane exposure) to completion of carotid ligation (at which point
      isoflurane exposure was also terminated). In the first part of the study, the ITL
      of each group was designated to be 5, 13, and 21 min. In the second part of the
      study, the ITL is designated to 4 min; however, continued isoflurane was used to
      make 5, 13, and 21 min isoflurane exposure for each group. Percentages of brain
      infarction were assessed at 48 h following surgery. Motor deficits were accessed
      by Rotarod test. Marked brain infarction was observed in the 5-min ITL group and
      a decrease of brain infarction observed in the 13-and 21-min groups (P<0.05). In
      the second part of the study, marked brain infarction was observed in the 5-min
      isoflurane exposure group, and a decrease of brain infarction was observed in
      each of the 13- and 21-min isoflurane exposure groups (P<0.05). Similar
      tendencies were observed in Rotarod tests than 5-min ITL and 5-min isoflurane
      groups showed more marked deficits (P<0.05). This study demonstrated that brain
      infarction inconsistency of the neonatal hypoxia-ischemia rat pup model is
      related to the operation time. The observed time-dependent decrease of brain
      infarction is correlated to the isoflurane exposure time. Shorter operation and
      isoflurane exposure improves this model consistency of brain infarction and motor
      deficits. 

PMID- 21892365
TI  - Variables Affecting the Gingival Embrasure Space in Aesthetically Important
      Regions: Differences between Central and Lateral Papillae.
AB  - This study evaluated different variables to determine their role in the
      appearance of the central and lateral upper jaw papillae. 292 interdental
      embrasures were examined. Personal variables were: age, smoke, and use of
      interproximal hygiene devices. The clinical characteristics were: tooth shape,
      periodontal biotype and papilla appearance. Radiographic measurements were: root
      to root distance at the cemento-enamel junction (horizontal distance), and bone
      crest to interdental contact point distance (vertical distance). The papilla
      recession increased with patient age. The horizontal distance of the central
      papilla was always greater (up to 1 mm) than that of the other papillae. The
      vertical distance of the central papilla was greater (up to 2 mm) than that of
      the other papillae for each class except for the normal one (Nordland & Tarnow
      classification). For vertical distances <=5 mm, papillae were almost always
      present; for distances up to 6 mm, the lateral papillae belonging to the normal
      class disappeared, while the central papilla remained in 11% of cases; central
      papillae of class 1 were present in larger proportions until a vertical distance
      of 8 mm. The present observational study shows that differences on clinical and
      radiographic determinants do exist between central and lateral papillae. This
      variance should be strictly taken in account for a harmonious and stable
      treatment outcome on this highly aesthetic area.

PMID- 21892366
TI  - Oral characteristics of trisomy 8 and monosomy 18: a case report.
AB  - Several reports described various mosaic chromosomal syndromes characterized by
      alterations originated by either an excess or deficit in the number of
      chromosomes. A case of mosaic trisomy 8 and monosomy 18 with significant
      involvement of the oral cavity is described, both in terms of general medicine
      and from a dental-oral perspective, and the treatment plan was planned and
      discussed.Regular follow-up visits enabled to verify significant improvement in
      all parameters of the patient's oral health, which urged us to press on with our
      quest to protect the right to health of patients affected by disabilities.

PMID- 21892367
TI  - Subpathotypes of Avian Pathogenic Escherichia coli (APEC) Exist as Defined by
      their Syndromes and Virulence Traits.
AB  - Avian pathogenic Escherichia coli (APEC) strains cause different types of
      systemic extraintestinal infections in poultry, collectively termed
      colibacillosis, which can cause significant economic losses in the poultry
      industry. To date, there have been no descriptions of genes or characteristics
      that allow for the classification of avian strains pathotypes responsible for
      causing specific diseases in their hosts. In this study we aimed to characterize
      avian E. coli strains representing 4 groups, including one of commensal strains
      (AFEC - Avian Fecal Escherichia coli) and 3 groups of APEC strains, where each
      group is responsible for causing a different disease syndrome in their respective
      hosts (septicemia, omphalitis and swollen head syndrome). We chose to examine
      several biological characteristics of these strains including: adhesion to
      eukaryotic cells, pathogenicity levels according to the lethal dose (50%) assay,
      phylogenetic group and virulence gene profiles. The comparison of strains based
      on these genotypic and phenotypic traits, using multivariate statisticals tools
      and complex networks, allowed us to infer information about the population
      structure of the studied groups. Our results indicate that APEC strains do not
      constitute a unique homogeneous group, but rather a structured set of subgroups,
      where each one is associated with a specific infectious syndrome which can
      possibly be used to define pathotypes or subpathotypes within APEC strains. These
      results offer new possibilities with which to study the genes responsible for
      various pathogenetic processes within APEC strains, and for vaccine development.
      It may be important to consider these subgroups when developing a vaccine in an
      effort for obtain cross protection, which has not yet been successfully
      accomplished when working with APEC strains.

PMID- 21892368
TI  - Advances and developments in the use of human mesenchymal stem cells - a few
      considerations.
AB  - One less visited area in musculoskeletal stem cell research is the effects of
      donor age on quality of stem cells. The prevalence of degenerative orthopaedic
      conditions is large, and the older population is likely to receive great benefit
      from stem cell therapies. There are many known growth factors involved in
      controlling and influencing stem cell growth which are also related to cell
      senescence. Of which, expressions are found to be altered in mesenchymal stem
      cells from older donors. Considerations must also be taken of these mechanisms
      which also have a role in cell cycle and tumour suppression.

PMID- 21892369
TI  - Integration of medical images into the digital hospital.

PMID- 21892370
TI  - Micro soft tissues visualization based on x-ray phase-contrast imaging.
AB  - The current imaging methods have a limited ability to visualize microstructures
      of biological soft tissues. Small lesions cannot be detected at the early stage
      of the disease. Phase contrast imaging (PCI) is a novel non-invasive imaging
      technique that can provide high contrast images of soft tissues by the use of X
      ray phase shift. It is a new choice in terms of non-invasively revealing soft
      tissue details. In this study, the lung and hepatic fibrosis models of mice and
      rats were used to investigate the ability of PCI in microstructures observation
      of soft tissues. Our results demonstrated that different liver fibrosis stages
      could be distinguished non-invasively by PCI. The three-dimensional morphology of
      a segment of blood vessel was constructed. Noteworthy, the blood clot inside the
      vessel was visualized in three dimensions which provided a precise description of
      vessel stenosis. Furthermore, the whole lung airways including the alveoli were
      obtained. We had specifically highlighted its use in the visualization and
      assessment of the alveoli. To our knowledge, this was the first time for non
      invasive alveoli imaging using PCI. This finding may offer a new perspective on
      the diagnosis of respiratory disease. All the results confirmed that PCI will be
      a valuable tool in biological soft tissues imaging.

PMID- 21892371
TI  - Automatic detection and classification of breast tumors in ultrasonic images
      using texture and morphological features.
AB  - Due to severe presence of speckle noise, poor image contrast and irregular lesion
      shape, it is challenging to build a fully automatic detection and classification
      system for breast ultrasonic images. In this paper, a novel and effective
      computer-aided method including generation of a region of interest (ROI),
      segmentation and classification of breast tumor is proposed without any manual
      intervention. By incorporating local features of texture and position, a ROI is
      firstly detected using a self-organizing map neural network. Then a modified
      Normalized Cut approach considering the weighted neighborhood gray values is
      proposed to partition the ROI into clusters and get the initial boundary. In
      addition, a regional-fitting active contour model is used to adjust the few
      inaccurate initial boundaries for the final segmentation. Finally, three textures
      and five morphologic features are extracted from each breast tumor; whereby a
      highly efficient Affinity Propagation clustering is used to fulfill the
      malignancy and benign classification for an existing database without any
      training process. The proposed system is validated by 132 cases (67 benignancies
      and 65 malignancies) with its performance compared to traditional methods such as
      level set segmentation, artificial neural network classifiers, and so forth.
      Experiment results show that the proposed system, which needs no training
      procedure or manual interference, performs best in detection and classification
      of ultrasonic breast tumors, while having the lowest computation complexity.

PMID- 21892372
TI  - The research of sequential images: rebuilding of gray (position) ~ time function
      on direction lines and their applications.
AB  - Contrasted with other information carriers, such as speech and text, images
      contains larger amount of information, especially in sequential images, that is
      waiting to be exploited, in particular the dynamic information of correlation,
      difference, and temporal relationship between different frames. This dynamic
      information contributes a great deal in analysis of 4D images. This paper
      proposes a method for detecting dynamic information from sequential images, based
      on the rebuilding of their gray (position)~time function on direction lines, an
      approach that has been analyzed and studied extensively on the setting of various
      direction lines. This method is based on motion that is presented on sequential
      images. In particular, the method, Omni directional M-mode Echocardiography
      system, which we have studied extensively, will be described leading to a robust
      way of diagnosing heart diseases.

PMID- 21892373
TI  - Application study of vascular interventional robotic mechanism for remote
      steering.
AB  - BACKGROUND: Recently, robotic systems have been introduced as a useful method for
      surgical procedures. But in the field of vascular interventional therapy, the
      development of robotic system is slower. OBJECTIVE: The purpose of the study is
      to verify the reliability and safety of vascular interventional robotic system
      used in angiography, by the way of in vitro preliminary experiments and animal
      experiments. METHOD: The approach is to employ a proprietary vascular
      interventional robot system to complete glass vessel models and animal angiogram
      experiments. This robot system consists of a console port (remote steering
      system), an assistant port (propelled and rotation system) and a hydraulic fixing
      device, upon which surgeons control remotely to make go forward and rotate in the
      glass vessel models and animal vessels, on the 3D operation interface.
      Consequently, the operation time and success rate are counted and evaluated.
      RESULT: In the glass vessel model experiments, the Catheter can enter various
      kinds of vessel models with inside diameter length greater than 3mm and angle
      less than 90(o). In the animal (adult dogs) experiments, surgeons can accomplish
      smoothly the angiogram of the renal artery, the vertebral renal and the arteria
      carotis communis, without any complications of surgery. CONCLUSION: The angiogram
      by using vascular interventional robot system is safe and reliable. Surgeons can
      finish the angiogram in part by remote operation, and the result of angiogram can
      meet a number of simple expectations. However without wire control and force
      feedback systems, the applicability of this kind of robot system is not flexible
      enough and need to be improved in the future.

PMID- 21892375
TI  - Autism and metabolic cytopathy.
AB  - LETTER TO THE EDITOR: Autism is a wide spectrum disorder and a lot of factors
      play role in the etiology. Autism may accompany some genetic disorders such as
      fragile X, tuberosclerosis, neurofibromatosis and phenylketonuria [1]. However,
      the absence of sufficient evidence on the etiological roles of environmental,
      neuroanatomical and biochemical factors has shifted the direction of research to
      genetics and cytology [2].

PMID- 21892374
TI  - Prototypes for content-based image retrieval in clinical practice.
AB  - Content-based image retrieval (CBIR) has been proposed as key technology for
      computer-aided diagnostics (CAD). This paper reviews the state of the art and
      future challenges in CBIR for CAD applied to clinical practice.We define
      applicability to clinical practice by having recently demonstrated the CBIR
      system on one of the CAD demonstration workshops held at international
      conferences, such as SPIE Medical Imaging, CARS, SIIM, RSNA, and IEEE ISBI. From
      2009 to 2011, the programs of CADdemo@CARS and the CAD Demonstration Workshop at
      SPIE Medical Imaging were sought for the key word "retrieval" in the title. The
      systems identified were analyzed and compared according to the hierarchy of gaps
      for CBIR systems.In total, 70 software demonstrations were analyzed. 5 systems
      were identified meeting the criterions. The fields of application are (i) bone
      age assessment, (ii) bone fractures, (iii) interstitial lung diseases, and (iv)
      mammography. Bridging the particular gaps of semantics, feature extraction,
      feature structure, and evaluation have been addressed most frequently.In specific
      application domains, CBIR technology is available for clinical practice. While
      system development has mainly focused on bridging content and feature gaps,
      performance and usability have become increasingly important. The evaluation must
      be based on a larger set of reference data, and workflow integration must be
      achieved before CBIR-CAD is really established in clinical practice.

PMID- 21892376
TI  - Normal Range of CD4 Cell Counts and Temporal Changes in Two HIVNegative Malawian
      Populations.
AB  - Longitudinal studies were carried out to determine trends in CD4 cell counts over
      a four year period in healthy HIV-negative adults in a rural (134 individuals)
      and an urban (80 individuals) site in Malawi, using TruCountTM and FACScountTM
      platforms. At baseline, median counts and 95% ranges were 890 (359-1954) cells
      per microlitre (MUl) and 725 (114-1074) cells/MUl respectively. 1.5% and 6%
      respectively had baseline counts below 350 cells/MUl and 1.5% and 2.5% below 250
      cells per MUl. Transient dips to below 250 cells/MUl were observed in seven
      individuals, with two individuals having persistently low CD4 counts over more
      than one year. Women and individuals from the urban site were significantly more
      likely to have "low CD4 count" (< 500 cells/MUl) even when adjusted for other
      factors. In common with neighbouring countries, HIV-negative populations in
      Malawi have CD4 counts considerably lower than European reference ranges, and
      healthy individuals may have persistently or transiently low counts. Within
      Malawi, ranges differ according to the selected population.

PMID- 21892377
TI  - Erosion in the Healthcare Safety Net: Impacts on Different Population Groups.
AB  - Safety net hospitals (SNHs) have played a critical role in the U.S. health system
      providing access to health care for vulnerable populations, in particular the
      Medicaid and uninsured populations. However, little research has examined how
      access for these populations changes when contraction of the safety net occurs.
      Institutional policies, such as hospital closure or ownership conversion, could
      affect the supply of minority health care providers, thus exacerbating
      disparities in outcomes. We use multilevel logistic modeling of person-level
      hospital discharge data to examine the effects of contractions in the California
      safety net over the period of 1990-2000 on access to care as measured by changes
      in ambulatory care sensitive condition (ACSC) admissions, using geographic
      methods to characterize proximity to a contraction event. We found that presence
      of a contraction event was associated with a statistically significant increase
      in the predicted probability of impeded access, with an increase of about 1% for
      Medicaid-insured populations and about 4-5% for the uninsured. The Medicaid
      insured group also maintained the highest rates of ACSC admissions over time,
      suggesting persistent access problems for this vulnerable group. This research is
      timely given continued budget problems in many states, where rising unemployment
      has increased the number of Medicaid enrollees by 6 million and uninsured
      individuals by 1.5 million, increasing pressure on remaining SNHs.

PMID- 21892378
TI  - Stem Cell Transplantation for Hematological Malignancies: Prospects for
      Personalized Medicine and Co-therapy with Mesenchymal Stem Cells.
AB  - Bone marrow transplantation is a form of cell therapy that has been in practice
      for decades for the treatment of hematological disorders and solid tumors.
      Immunosuppressive therapy has been a mainstay for treatment, but the severity of
      the adverse effects has made it an undesirable choice. Mesenchymal stem cells
      (MSCs), which reside in the vascular regions of the bone marrow, have been shown
      to serve as cellular support for the hematopoietic stem cell (HSC) niche.
      Furthermore, the immune suppressive properties of MSCs have been explored in the
      treatment of inflammatory and autoimmune disorders. Thus, co-therapy with MSCs
      has been shown to facilitate engraftment of hematopoietic cells by suppressive
      graft versus host disease (GvHD). Although the mechanism by which MSCs suppress
      GvHD is unclear, the experimental evidence suggests that this partly occurs by
      modulation of immune response such as the induction of regulatory T cells. This
      paper discusses the role of MSCs as co-therapy for the future of stem cell
      transplantation, with the overarching theme of personalized medicine for cell
      based health interventions.

PMID- 21892380
TI  - STRUCTURED, SPARSE REGRESSION WITH APPLICATION TO HIV DRUG RESISTANCE.
AB  - We introduce a new version of forward stepwise regression. Our modification finds
      solutions to regression problems where the selected predictors appear in a
      structured pattern, with respect to a predefined distance measure over the
      candidate predictors. Our method is motivated by the problem of predicting HIV-1
      drug resistance from protein sequences. We find that our method improves the
      interpretability of drug resistance while producing comparable predictive
      accuracy to standard methods. We also demonstrate our method in a simulation
      study and present some theoretical results and connection.

PMID- 21892381
TI  - A joint model of longitudinal and competing risks survival data with
      heterogeneous random effects and outlying longitudinal measurements.
AB  - This article proposes a joint model for longitudinal measurements and competing
      risks survival data. The model consists of a linear mixed effects sub-model with
      t-distributed measurement errors for the longitudinal outcome, a proportional
      cause-specific hazards frailty sub-model for the survival outcome, and a
      regression sub-model for the variance-covariance matrix of the multivariate
      latent random effects based on a modified Cholesky decomposition. A Bayesian MCMC
      procedure is developed for parameter estimation and inference. Our method is
      insensitive to outlying longitudinal measurements in the presence of non
      ignorable missing data due to dropout. Moreover, by modeling the variance
      covariance matrix of the latent random effects, our model provides a useful
      framework for handling high-dimensional heterogeneous random effects and testing
      the homogeneous random effects assumption which is otherwise untestable in
      commonly used joint models. Finally, our model enables analysis of a survival
      outcome with intermittently measured time-dependent covariates and possibly
      correlated competing risks and dependent censoring, as well as joint analysis of
      the longitudinal and survival outcomes. Illustrations are given using a real data
      set from a lung study and simulation.

PMID- 21892379
TI  - Overview of Basic Mechanisms of Cardiac Arrhythmia.

PMID- 21892382
TI  - SkinScan(c): A PORTABLE LIBRARY FOR MELANOMA DETECTION ON HANDHELD DEVICES.
AB  - We have developed a portable library for automated detection of melanoma termed
      SkinScan(c) that can be used on smartphones and other handheld devices. Compared
      to desktop computers, embedded processors have limited processing speed, memory,
      and power, but they have the advantage of portability and low cost. In this study
      we explored the feasibility of running a sophisticated application for automated
      skin cancer detection on an Apple iPhone 4. Our results demonstrate that the
      proposed library with the advanced image processing and analysis algorithms has
      excellent performance on handheld and desktop computers. Therefore, deployment of
      smartphones as screening devices for skin cancer and other skin diseases can have
      a significant impact on health care delivery in underserved and remote areas.

PMID- 21892383
TI  - Impact of Absolute Stereochemistry on the Antiangiogenic and Antifungal
      Activities of Itraconazole.
AB  - Itraconazole is used clinically as an antifungal agent and has recently been
      shown to possess antiangiogenic acitivity. Itraconazole has three chiral centers
      that give rise to eight stereoisomers. The complete role of stereochemistry in
      the two activities of itraconazole, however, has not been addressed adequately.
      For the first time, all eight stereoisomers of itraconazole (1a-1h) have been
      synthesized and evaluated for activity against human endothelial cell
      proliferation and for antifungal activity against five fungal strains. Distinct
      antiangiogenic and antifungal activity profiles of the trans- stereoisomers,
      especially 1e and 1f, suggest different molecular mechanisms underlying the anti
      angiogenic and anti-fungal activities of itraconazole.

PMID- 21892384
TI  - In vitro Selection of DNA Aptamers to Glioblastoma Multiforme.
AB  - Aptamer probes for specific recognition of glioblastoma multiforme were generated
      using a repetitive and broad cell-SELEX-based procedure without negative
      selection. The 454 sequencing technology was used to monitor SELEX, and
      bioinformatics tools were used to identify aptamers from high throughput data. A
      group of aptamers were generated that can bind to target cells specifically with
      dissociation constants (K(d)) in the nanomolar range. Selected aptamers showed
      high affinity to different types of glioblastoma cell lines, while showing little
      or no affinity to other cancer cell lines. The aptamers generated in this study
      have potential use in different applications, such as probes for diagnosis and
      devices for targeted drug delivery, as well as tools for molecular marker
      discovery for glioblastomas.

PMID- 21892385
TI  - The Prevalence of Undetected Vertebral Fracture in Patients with Back Pain by
      Dual-Energy X-ray Absorptiometry (DXA) of the Lateral Thoracic and Lumbar Spine.
AB  - STUDY DESIGN: This is a prospective study. PURPOSE: This study is conducted to
      determine the prevalence of unrecognized vertebral fracture (VF) in patients who
      present with back pain. OVERVIEW OF LITERATURE: VF is often unrecognized, and
      significantly increases the risk of further fractures. Unfortunately, the
      patients at a high risk for VF usually do not receive adequate therapy to reduce
      the fracture risk. METHODS: This is a prospective study of 344 patients who
      presented with back pain from April 2008 to May 2009. The patients underwent dual
      energy X-ray absorptiometry (DXA) evaluation and vertebral fracture assessment
      from T4 to L4 using a hologic densitometer. RESULTS: Three hundred forty four of
      386 patients who presented with back pain were included. Forty two patients were
      excluded because of a prior history of VF or the lack of written consent. Most of
      the patients were female (95.3%). The mean age of the patients was 58.21 +/-
      11.74 years. According to the World Health Organization definition (based on the
      T-score), 13.4% of the patients had normal lumbar spine bone mineral density
      (BMD). 27.9% of them were osteopenic and 58.7% were osteoporotic. The overall
      prevalence of VF, as established by lateral vertebral assessment, was 39% (n =
      134). Moreover, 62.6% (n = 84) of the patients with VF had more than one fracture
      and 64.1% (n = 86) of them had Grade 2 or 3 fracture. CONCLUSIONS: We recommend
      performing not only DXA scanning for BMD evaluation, but also VFA by DXA in old
      patients with back pain.

PMID- 21892386
TI  - Posterior direct decompression and fusion of the lower thoracic and lumbar
      fractures with neurological deficit.
AB  - STUDY DESIGN: A retrospective study. PURPOSE: To analyze the treatment outcome of
      patients with lower thoracic and lumbar fractures combined with neurological
      deficits. OVERVIEW OF LITERATURE: Although various methods of the surgical
      treatment for lower thoracic and lumbar fractures are used, there has been no
      surgical treatment established as a superior option than others. METHODS: Between
      March 2001 and August 2009, this study enrolled 13 patients with lower thoracic
      and lumbar fractures who underwent spinal canal decompression by removing
      posteriorly displaced bony fragments via the posterior approach and who followed
      up for more than a year. We analyzed the difference between the preoperative and
      postoperative extents of canal encroachment, degrees of neurologic deficits and
      changes in the local kyphotic angle. RESULTS: The average age of the patients was
      37 years. There were 10 patients with unstable burst factures and 3 patients with
      translational injuries. Canal encroachment improved from preoperative average of
      84% to 9% postoperatively. Local kyphosis also improved from 20.5 degrees  to 1.5
      degrees . In 92% (12/13) of the patients, neurologic deficit improved more than
      Frankel grade 1 and an average improvement of 1.7 grade was observed.
      Deterioration of neurologic symptoms was not observed. Although some loss of
      reduction of kyphotic deformity was observed at the final follow-up, serious
      complications were not observed. CONCLUSIONS: When posteriorly displaced bony
      fragments were removed by the posterior approach, neurological recovery could be
      facilitated by adequate decompression without serious complications. The
      posterior direct decompression could be used as one of treatments for lower
      thoracic and lumbar fractures combined with neurologic injuries.

PMID- 21892387
TI  - The use of titanium mesh cages in the reconstruction of anterior column defects
      in active spinal infections: can we rest the crest?
AB  - STUDY DESIGN: Retrospective clinical series. PURPOSE: To assess whether titanium
      cages are an effective alternative to tricortical iliac crest bone graft for
      anterior column reconstruction in patients with active pyogenic and tuberculous
      spondylodiscitis. OVERVIEW OF LITERATURE: The use of metal cages for anterior
      column reconstruction in patients with active spinal infections, though
      described, is not without controversy. METHODS: Seventy patients with either
      tuberculous or pyogenic vertebral osteomyelitis underwent a single staged
      anterior debridement, reconstruction of the anterior column with titanium mesh
      cage and adjuvant posterior instrumentation. The lumbar spine was the predominant
      level of involvement. Medical co-morbidities were seen in 18 (25.7%) patients. A
      significant neurological deficit was seen in 32 (45.7%) patients. At follow up
      patients were assessed for healing of disease, bony fuson, and clinical outcome
      was assessed using Macnab's criteria. RESULTS: Final follow up was done on 64
      (91.4%) patients at a mean average of 25 months (range, 12 to 110 months).
      Pathologic organisms could be identified in 42 (60%) patients. Forty two (60%)
      patients had histopathological findings consistent with tuberculosis. Thirty of
      32 (93.7%) patients showed neurological recovery. The surgical wound healed
      uneventfully in 67 (95.7%) patients. Bony fusion was seen in 60 (93.7%) patients.
      At final follow up healing of infection was seen in all patients. As per Macnab's
      criteria 61 (95.3%) patients reported a good to excellent outcome. CONCLUSIONS:
      Inspite of the theoretical risks, titanium cages are a suitable alternative to
      autologous tricortical iliac crest bone graft in patients with active spinal
      infections.

PMID- 21892388
TI  - Efficacy of unipedicular baloon kyphoplasty for treatment of multiple myeloma
      vertebral lesions.
AB  - STUDY DESIGN: A retrospective cohort study. PURPOSE: To analyze differences in
      between the unipedicular vs. bipedicular balloon kyphoplasty for the treatment of
      multiple myeloma lesions. OVERVIEW OF LITERATURE: Both vertebroplasty and
      kyphoplasty are reported to be effective for the treatment of vertebral
      compression fractures in multiple myeloma patients. Kyphoplasty is often
      performed with a bipedicular approach while vertebroplasty with a monopedicular
      approach. Monopedicular kyphoplasty is investigated as a viable surgical
      technique alternatively in comparison with the bipedicular method. METHODS: We
      performed 37 vertebral body augmentation procedures, 18 vertebroplasty (group A)
      and 19 kyphoplasty, 9 unipedicular approaches (group B1) and 10 bipedicular
      approaches (group B2), on 14 patients affected by multiple myeloma with a mean
      clinical and radiographic follow up of more than 12 months. RESULTS: Both
      kyphoplasty techniques lead to a better postoperative improvement of the
      vertebral height and kyphotic deformity if compared with the vertebroplasty, with
      a statistical significance for the body height restoration only (p = 0.0066). The
      unipedicular and the bipedicular kyphoplasty have similar results in term of
      kyphotic deformity correction and height restoration. The 85.7% (12/14) of the
      patients had an immediate improvement of the pain and no difference between the
      vertebroplasty and kyphoplasty groups were observed regarding the pain. We
      observed a 24.3% of cement leakage in all groups with no clinical symptoms and
      noticed that the risk of extravasations was higher in multilevel treatment, in
      bipedicular kyphoplasty procedures and in patients not treated previously with a
      bone marrow transplant. CONCLUSIONS: Both vertebroplasty and kyphoplasty are
      effective in treating vertebral compression fracture due to multiple myeloma.
      Unipedicular kyphoplasty could give equivalent results as with bipedicular
      kyphoplasty in multilevel disease, aiming only to restore the sagittal alignment
      of the spine and the height of the vertebral body especially at the thoracolumbar
      spinal segment.

PMID- 21892389
TI  - Comparative study of clinical outcomes of anterior cervical discectomy and fusion
      using autobone graft or cage with bone substitute.
AB  - STUDY DESIGN: A retrospective study. PURPOSE: To compare the clinical and
      radiological outcomes of autogenous bone graft and cage with bone substitute for
      anterior cervical discectomy and fusion. OVERVIEW OF LITERATURE: The clinical
      outcomes of cage with bone substitute for anterior cervical discectomy and fusion
      is satisfactory. METHODS: Eighty four patients who underwent cervical spine
      surgery between February 2004 and April 2009 were included. Fifty-nine patients
      were approached anteriorly and underwent anterior cervical discectomy and fusion
      by the Smith-Robinson method (Group A), and 25 patients underwent fusion by
      decompression of the cervical spine and cage with bone substitute (Group B). We
      measured and evaluated the postoperative period until patients were able to
      ambulate, for pre- and postoperative symptomatic improvement, postoperative
      complications, pre- and postoperative change of lordosis, degree of endplate
      collapse or subsidence, and fusion rate and period of union. RESULTS: By
      Robinson's criteria, respectively 45, 10 and 4 patients in Group A experienced
      excellent, good and fair symptomatic improvement, and respectively 19, 5 and 1
      patients in Group B experienced excellent, good and fair symptomatic improvement.
      The postoperative period in which patients became ambulant and the period of
      hospital stay was significantly shorter in Group B. Increase of lordosis at final
      follow up after surgery was significantly larger in Group A, as was the fusion
      period. Significantly more endplate collapse occurred in Group B. CONCLUSIONS: Of
      patients who had anterior cervical discectomy and fusion, results of both groups
      were both satisfactory.

PMID- 21892390
TI  - A levering technique for open reduction of traumatic unilateral locked facets of
      cervical spine: technical note.
AB  - Reduction of traumatic unilateral locked facets of the cervical spine can be
      accomplished by closed or open means. If closed reduction is unsuccessful, then
      open reduction is indicated. The previously described techniques of open
      reduction of a unilateral locked facets of the cervical spine in the literature
      included drilling facet, forceful manipulation or using special equipment. We
      describe a reduction technique that uses a basic spinal curette, in a forceless
      manner, and it does not need facet drilling. We have successfully used this
      technique in 5 consecutive patients with unilateral locked facets. There have
      been no complications related to this technique.

PMID- 21892391
TI  - Risk factors of new compression fractures in adjacent vertebrae after
      percutaneous vertebroplasty.
AB  - STUDY DESIGN: Retrospective study. PURPOSE: To evaluate risk factors related to
      the development of new fractures in adjacent vertebrae after percutaneous
      vertebroplasty. OVERVIEW OF LITERATURE: Recent reports indicate that undue
      numbers of new fractures in adjacent vertebral bodies occur after percutaneous
      vertebroplasty. METHODS: One hundred four of 369 patients who underwent
      percutaneous vertebroplasty were followed for over 1 year. Fifty-four patients
      (51.9%) subsequently suffered from adjacent vertebral fractures. Age, lumbar
      lordotic angle, sacral slope, pelvic tilt, pelvic incidence, bone mineral
      density, amounts of cement injected, the restoration of vertebral height,
      kyphotic angle differences preexisting fracture, and intradiscal cement leakage
      were noted. RESULTS: Average bone mineral density was -3.52 in the fracture group
      and -2.91 in the fracture-free group; the risk of adjacent vertebral fracture
      increased as bone mineral density decreased (p < 0.05). Intradiscal cement
      leakage occurred in 18 patients (33.3%) in the fracture group, indicating that
      the risk of adjacent vertebral fracture increased with intradiscal cement
      leakage. In addition, 36 patients (66.7%) in the fracture group had a pre
      existing fracture; thus, the presence of a preexisting fracture was found to be
      significantly associated with an increased risk of an adjacent vertebral fracture
      (p < 0.05). Higher restoration rates are associated with a greater likelihood of
      developing adjacent vertebral fractures (p < 0.05). CONCLUSIONS: The factors
      found to contribute significantly to new fractures in adjacent vertebral bodies
      after percutaneous vertebroplasty were a lower bone mineral density, a greater
      restoration rate of vertebral height, a pre-existing fracture, and intradiscal
      cement leakage.

PMID- 21892392
TI  - Successful Bone Union Following Calcium Phosphate Cement-Assisted Percutaneous
      Transpedicular Balloon Kyphoplasty of a Large Interbody Cleft on Long-term
      Hemodialysis Patient.
AB  - A 68-year-old diabetic man, who had been on dialysis for 3 years, suffered a five
      week history of severe back pain that was unresponsive to bed rest, analgesics,
      and bracing. The vertebral cleft formed by an injury gradually increased in size
      on sequential plain films. Hence, he underwent calcium phosphate cement-assisted
      percutaneous transpedicular balloon kyphoplasty to treat a painful interbody
      vacuum cleft. Immediate pain relief and firm bone union were obtained.

PMID- 21892393
TI  - Primary Lumbo-sacral Spinal Epidural Non-Hodgkin's Lymphoma: A Case Report and
      Review of Literature.
AB  - We present a case of 24-year-old male presented with low back pain radiating to
      the left lower limb, tingling numbness and weakness of 6 months duration.
      Magnetic resonance imaging scan with contrast reveals an extradural mass at
      lumbosacral region. Patient was operated with laminectomy and complete excision
      of the lesion was done. Patient's radicular pain relieved following the surgery
      and weakness also improved. Histopathology was suggestive of non-Hodgkin's
      lymphoma. Patient received chemotherapy which was followed by radiotherapy.
      Primary Non-Hodgkin's lymphoma of the lumbosacral spinal epidural tissue is an
      uncommon lesion. Lymphoma involves the central nervous system in 5-11% of cases
      either at presentation of the disease or during its course. The spinal epidural
      tissue is involved primarily in 0.1-3.3% of cases with spinal cord compression
      being the commonest presentation. Excision of the lesion followed by chemotherapy
      and radiotherapy is required to achieve cure.

PMID- 21892394
TI  - Hemorrhagic facet cyst in the lumbar spine causing contralateral leg symptoms: a
      case report.
AB  - Here we present a case of hemorrhagic lumbar facet cyst presenting with
      progressive radiculopathy only on the contralateral side. If a patient has
      previous back pain or neuropathy for several months and then suddenly
      deteriorates, hemorrhagic facet cyst of the lumbar spine should be part of the
      differential diagnosis. However, as in the present case, we should be aware that
      there is a possibility of a contralateral lesion.

PMID- 21892395
TI  - Selected abstracts from the annual meeting of the scandinavian society of
      periodontology, bergen, june 9-12 2011.

PMID- 21892396
TI  - Thromboxane A2 synthetase inhibitor plus low dose aspirin : can it be a salvage
      treatment in acute stroke beyond thrombolytic time window.
AB  - OBJECTIVE: There is no proven regimen to reduce the severity of stroke in
      patients with acute cerebral infarction presenting beyond the thrombolytic time
      window. Ozagrel sodium, a selective thromboxane A2 synthetase inhibitor, has been
      known to suppress the development of infarction. The antiplatelet effect is
      improved when aspirin is used together with a thromboxane synthetase inhibitor.
      METHODS: Patients with non-cardiogenic acute ischemic stroke who were not
      eligible for thrombolysis were randomly assigned to two groups; one group
      received ozagrel sodium plus 100 mg of aspirin (group 1, n=43) and the other 100
      mg of aspirin alone (group 2, n=43). Demographic data, cardiovascular risk
      factors, initial stroke severity [National Institute of Health Stroke Scale
      (NIHSS) and motor strength scale] and stroke subtypes were analyzed in each
      group. Clinical outcomes were analyzed by NIHSS and motor strength scale at 14
      days after the onset of stroke. RESULTS: There were no significant differences in
      the mean age, gender proportion, the prevalence of cardiovascular risk factors,
      stroke subtypes, and baseline neurological severity between the two groups.
      However, the clinical outcome for group 1 was much better at 14 days after the
      onset of stroke compared to group 2 (NIHSS score, p=0.007, Motor strength scale
      score, p<0.001). There was one case of hemorrhagic transformation in group 1, but
      there was no statistically significant difference in bleeding tendency between
      two groups. CONCLUSION: In this preliminary study, thromboxane A2 synthetase
      inhibitor plus a low dose of aspirin seems to be safe and has a favorable outcome
      compared to aspirin alone in patients with acute ischemic stroke who presented
      beyond the thrombolytic time window.

PMID- 21892397
TI  - Clinical features of acute subdural hematomas caused by ruptured intracranial
      aneurysms.
AB  - OBJECTIVE: Spontaneous acute subdural hematomas (aSDH) secondary to ruptured
      intracranial aneurysms are rarely reported. This report reviews the clinical
      features, diagnostic modalities, treatments, and outcomes of this unusual and
      often fatal condition. METHODS: We performed a database search for all cases of
      intracranial aneurysms treated at our hospital between 2005 and 2010. Patients
      with ruptured intracranial aneurysms who presented with aSDH on initial computed
      tomography (CT) were selected for inclusion. The clinical conditions, radiologic
      findings, treatments, and outcomes were assessed. RESULTS: A total of 551
      patients were treated for ruptured intracranial aneurysms during the review
      period. We selected 23 patients (4.2%) who presented with spontaneous aSDH on
      initial CT. Ruptured aneurysms were detected on initial 3D-CT angiography in all
      cases. All ruptured aneurysms were located in the anterior portion of the circle
      of Willis. The World Federation of Neurosurgical Societies grade on admission was
      V in 17 cases (73.9%). Immediate decompressive craniotomy was performed 22 cases
      (95.7%). Obliteration of the ruptured aneurysm was achieved in all cases. The
      Glasgow outcome scales for the cases were good recovery in 5 cases (21.7%),
      moderate disability to vegetative in 7 cases (30.4%), and death in 11 cases
      (47.8%). CONCLUSION: Spontaneous aSDH caused by a ruptured intracranial aneurysm
      is rare pattern of aneurysmal subarachnoid hemorrhage. For early detection of
      aneurysm, 3D-CT angiography is useful. Early decompression with obliteration of
      the aneurysm is recommended. Outcomes were correlated with the clinical grade and
      CT findings on admission.

PMID- 21892398
TI  - Predictable factors for dural tears in lumbar burst fractures with vertical
      laminar fractures.
AB  - OBJECTIVE: The purpose of the present study was to determine the incidence of
      dural tears and predictable factors suggesting dural tears in patients who had
      lumbar burst fractures with vertical laminar fractures. METHODS: A retrospective
      review was done on thirty-one patients who underwent operative treatment for
      lumbar burst fractures with vertical laminar fractures between January 2003 and
      December 2008. All patients were divided into two groups according to existence
      of dural tears, which were surgically confirmed; 21 patients with dural tears and
      10 patients without dural tears. Clinical and radiographic findings were analyzed
      for their association with dural tears. RESULTS: Among a total of 31 patients,
      dural tears were detected in 21 (67%) patients. A preoperative neurological
      deficits and mean separation distances of the edges in laminar fractures were
      found to be the reliable factors of dural tears (p=0.001 and 0.002,
      respectively). Decreased ratio of the central canal diameter and interpedicular
      distance were also the reliable factors suggesting dural tears (p=0.006 and
      0.015, respectively). However, dural tears showed no significant association with
      age, sex, level of injury, absence of a posterior fat pad signal, the angle of
      retropulsed segment, or site of laminar fracture. CONCLUSION: Our study of lumbar
      burst fracture combined laminar fracture revealed that dural tears should be
      ruled out in cases of a preoperative neurological deficits, wide separation of
      the laminar fracture, severe canal encroachment, and wider interpedicular
      distance.

PMID- 21892399
TI  - Clinical outcomes of halo-vest immobilization and surgical fusion of odontoid
      fractures.
AB  - OBJECTIVE: In the present study, authors retrospectively reviewed the clinical
      outcomes of halo-vest immobilization (HVI) versus surgical fixation in patients
      with odontoid fracture after either non-surgical treatment (HVI) or with surgical
      fixation. METHODS: From April 1997 to December 2008, we treated a total of 60
      patients with upper cervical spine injuries. This study included 31 (51.7%)
      patients (22 men, 9 women; mean age, 39.3 years) with types II and III odontoid
      process fractures. The average follow-up was 25.1 months. We reviewed digital
      radiographs and analyzed images according to type of injury and treatment
      outcomes, following conservative treatment with HVI and surgical management with
      screw fixation. RESULTS: There were a total of 31 cases of types II and III
      odontoid process fractures (21 odontoid type II fractures, 10 type III
      fractures). Fifteen patients underwent HVI (10 type II fractures, 5 type III
      fractures). Nine (60%) out of 15 patients who underwent HVI experienced
      successful healing of odontoid fractures. The mean period for bone healing was
      20.2 weeks. Sixteen patients underwent surgery including anterior screw fixation
      (6 cases), posterior C1-2 screw fixation (8), and transarticular screw fixation
      (2) for healing the odontoid fractures (11 type II fractures, 5 type III
      fractures). Fifteen (93.8%) out of 16 patients who underwent surgery achieved
      healing of cervical fractures. The average bone healing time was 17.6 weeks.
      CONCLUSION: The overall healing rate was 60% after HVI and 93.8% with surgical
      management. Patients treated with surgery showed a higher fusion rate and shorter
      bony healing time than patients who received HVI. However, prospective studies
      are needed in the future to define better optimal treatment and cost-effective
      perspective for the treatment of odontoid fractures.

PMID- 21892400
TI  - Indocyanine green videoangiography for confirmation of bypass graft patency.
AB  - OBJECTIVE: The aim of the study is to determine the efficacy of indocyanine green
      (ICG) videoangiography for confirmation of vascular anastomosis patency in both
      extracranial-intracranial and intracranial-intracranial bypasses. METHODS:
      Intraoperative ICG videoangiography was used as a surgical adjunct for 56
      bypasses in 47 patients to assay the patency of intracranial vascular
      anastomosis. These patients underwent a bypass for cerebral ischemia in 31
      instances and as an adjunct to intracranial aneurysm surgery in 25. After
      completion of the bypass, ICG was administered to assess the patency of the
      graft. The findings on ICG videoangiography were then compared to intraoperative
      and/or postoperative imaging. RESULTS: ICG provided an excellent visualization of
      all cerebral arteries and grafts at the time of surgery. Four grafts were
      determined to be suboptimal and were revised at the time of surgery. Findings on
      ICG videoangiography correlated with intraoperative and/or postoperative imaging.
      CONCLUSION: ICG videoangiography is rapid, effective, and reliable in determining
      the intraoperative patency of bypass grafts. It provides intraoperative
      information allowing revision to reduce the incidence of technical errors that
      may lead to early graft thrombosis.

PMID- 21892401
TI  - Morphometric study of the upper thoracic sympathetic Ganglia.
AB  - OBJECTIVE: Morphometric data for the sympathetic ganglia (SG) of the upper
      thoracic spine was investigated to identify the exact location of the SG in order
      to reduce normal tissue injury in the thoracic cavity during thoracoscopic
      sympathectomy. METHODS: In 46 specimens from 23 formalin-fixed adult cadavers,
      the authors measured the shortest distance from the medial margin of the T1, T2
      and T3 SG to the most prominent point and medial margin of the corresponding rib
      heads, and to the lateral margin of the longus colli muscle. In addition, the
      distance between the most prominent point of the rib head and the lateral margin
      of longus colli muscle and the width of each SG were measured. RESULTS: The
      shortest distance from the medial margin of the SG to the prominent point of
      corresponding rib head was on average 1.9 mm on T1, 4.2 mm, and 4.1 mm on T2, T3.
      The distance from the medial margin of the SG to the medial margin of the
      corresponding rib head was 4.2 mm on T1, 5.9 mm, and 6.3 mm on T2, T3. The mean
      distance from the medial margin of the SG to the lateral margin of the longus
      colli muscle was 6.7 mm on T1, 8.8 mm, 9.9 and mm on T2, T3. The mean distance
      between the prominent point of the rib head and the lateral margin of the longus
      colli muscle was 4.8 mm on T1, 4.6 mm, and 5.9 mm on T2, T3. The mean width of SG
      was 6.1 mm on T1, 4.1 mm, and 3.1 mm on T2, T3. CONCLUSION: We present
      morphometric data to assist in surgical planning and the localization of the
      upper thoracic SG during thoracoscopic sympathectomy.

PMID- 21892402
TI  - The efficacy of scalene injection in thoracic outlet syndrome.
AB  - OBJECTIVE: To evaluate the efficacy of scalene injection in patients with
      thoracic outlet syndrome. METHODS: We selected 142 patients diagnosed with
      thoracic outlet syndrome between January 2005 and October 2009. We performed a
      series of scalene injection with conservative treatment in all cases. Patients
      rated their pain degrees using a visual analogue scale. We also evaluated the
      time to return to everyday life and work, and patients' functional capacity.
      RESULTS: There were no complications or instances of inadvertent somatic or
      sympathetic ganglionic blockade after scalene injection. Overall, 111 patients
      (76.5%) experienced improved symptoms after the first set of scalene injection
      and 128 patients (88.2%) improved after scalene injection followed by
      conservative treatment. Of the 68 patients who returned to work during the study
      period, 54 returned within 1 week, and 62 within 2 weeks. Of those who returned
      to work, 61 reported nearly full functional capacity. We found that scalene
      injection was more effective in cases of thoracic outlet syndrome related to
      trauma than in those related to work-related repetitive stress. CONCLUSION: In
      patients with thoracic outlet syndrome, scalene injection effectively reduces
      pain. We recommend scalene injection as an adjunct to conservative treatment.

PMID- 21892403
TI  - Significance of clopidogrel resistance related to the stent-assisted angioplasty
      in patients with atherosclerotic cerebrovascular disease.
AB  - OBJECTIVE: To evaluate the prevalence and risk factors of clopidogrel resistance,
      and association between thromboembolic complications and clopidogrel resistance
      in patient with stent-assisted angioplasty for atherosclerotic cerebrovascular
      disease. METHODS: Between September 2006 and June 2008, clopidogrel resistance
      test was performed on 41 patients who underwent stent-assisted angioplasty for
      atherosclerotic cerebrovascular disease. It was performed before drug
      administration and about 12 hours after drug administration (loading dose : 300
      mg, maintain dose : 75 mg). Two patients were excluded, and 41 patients were
      included (mean : 67.59+/-7.10 years, age range : 41-79). Among 41 patients, 18
      patients had intracranial lesions, and 23 had extracranial lesions. We evaluated
      the prevalence, risk factors and complications related to clopidogrel resistance.
      RESULTS: Twenty-one patients (51.2%) showed clopidogrel resistance [intracranial
      : 10 patients (55.6%), extracranial : 11 patients (47.8%)] and no clopidogrel
      resistance was seen in 20 patients. Hypercholesterolemia was an indepedent risk
      factor of clopidogrel resistance. Stent-assisted angioplasty was technically
      successful in all patients, but acute in-stent thrombosis occurred in 5 patients
      with intracranial lesions (4 patients with clopidogrel resistance and 1 without
      clopidogrel resistance). Acute thrombi were completely lysed after intra-arterial
      infusion of abciximab. CONCLUSION: There was relatively high prevalence of
      clopidogrel resistance in patients with atherosclerotic cerebrovascular disease.
      Hypercholesterolemia was an independent predictive factor of clopidogrel
      resistance. Acute in-stent thrombosis was more frequently seen in the clopidogrel
      resistant group. Therefore, clopidogrel resistance test should be performed to
      avoid thromboembolic complications related to stent-assisted angioplasty for
      atherosclerotic cerebrovascular disease, especially patients with
      hypercholeterolemia and intracranial lesion.

PMID- 21892404
TI  - Serious Blood-Brain Barrier Disruption after Coil Embolization of Unruptured
      Intracranial Aneurysm : Report of Two Cases and Role of Immediate
      Postembolization CT Scan.
AB  - Abnormal contrast enhancement on brain computed tomography (CT) scan after
      diagnostic or interventional angiography is not rare, and has known to be induced
      by temporary blood-brain barrier (BBB) disruption from contrast media.
      Furthermore, it has been regarded as clinically subtle, but reported to have no
      symptom or mild transient symptoms. However, we recently experienced two cases of
      serious BBB disruption during the acute period after coiling of an unruptured
      intracranial aneurysm. One patient presented with an unruptured paraclinoid
      internal carotid artery (ICA) aneurysm on the right and the other with an
      unruptured right supraclinoid ICA aneurysm. Both patients showed similar findings
      on immediate postembolization CT scan and clinical courses after coiling. Typical
      radiological, clinical characteristics of BBB disruption were described. In
      addition, the role of immediate postembolization CT scan are also discussed.

PMID- 21892406
TI  - Medulloblastoma manifesting as sudden sensorineural hearing loss.
AB  - We present a rare case of medulloblastoma which presented with unilateral sudden
      sensorineural hearing loss as an initial symptom. A 19-year-old man was admitted
      to our hospital with a chief complaint of dizziness and facial numbness on the
      right side. His illness had begun two years previously with sudden hearing loss
      on the right side, for which he had been treated as an idiopathic sudden hearing
      loss. Magnetic resonance imaging demonstrated abnormal signals located mainly in
      the right middle cerebellar peduncle. We performed partial resection of the tumor
      by suboccipital craniotomy. The histopathological diagnosis was medulloblastoma.
      Intrinsic brain tumor is an extremely rare cause of sudden sensorineural hearing
      loss and is therefore easily overlooked as was in the present case. The present
      case highlights not only the need to evaluate patients with sudden sensorineural
      hearing loss by magnetic resonance imaging but also the importance of paying
      attention to intrinsic lesions involving the brainstem. Although this condition
      like the presented case might be rare, intrinsic brain tumor should be considered
      as a potential cause of sudden sensorineural hearing loss, as it may be easily
      missed leading to a delay in appropriate treatment.

PMID- 21892405
TI  - Endovascular treatment using graft-stent for pseudoaneurysm of the cavernous
      internal carotid artery.
AB  - A 57-year-old man presented with a 2-day history of left oculomotor palsy.
      Digital subtraction angiography revealed a pseudoaneurysm of the left cavernous
      internal carotid artery (ICA) measuring 37*32 mm. The pseudoaneurysm was treated
      with a balloon expandable graft-stent to occlude the aneurysmal neck and preserve
      the parent artery. A post-procedure angiogram confirmed normal patency of the ICA
      and complete sealing of the aneurysmal neck with no opacification of the sac.
      After the procedure, the oculomotor palsy improved gradually, and had completely
      resolved 3 months after the procedure. A graft-stent can be an effective
      treatment for a pseudoaneurysm of the cavernous ICA with preservation of the
      parent artery.

PMID- 21892407
TI  - Foraminal synovial cyst associated with ankylosing spondylitis.
AB  - Ankylosing spondylitis (AS) is frequently associated with inflammatory lesions of
      the spine and continuous fatigue stress fractures; however, an association with
      an intraspinal synovial cyst has not been previously reported. A 55-year-old man
      with a five year history of AS who presented with back pain and a right
      radiculopathy was admitted to the hospital. Five years previously, he underwent a
      percutaneous vertebroplasty for an osteoporotic L1 compression fracture, and was
      diagnosed with AS at that time. Plain radiographs showed aggravated kyphosis and
      a stress fracture through the ossified posterior element, below the prior
      vertebroplasty. Magnetic resonance images revealed a right foraminal cystic
      lesion at the L2-L3 level with effacement of the nerve root. A 1.6 cm cystic
      lesion that appeared to arise from the L2-L3 facet joint without direct
      communication was excised from the L2-L3 foramen. Pathological examination
      confirmed synovial cyst. The patient's symptoms resolved immediately after
      surgery except for a mild dysesthesia of the right leg. We report herein a rare
      case of foraminal synovial cyst associated with AS accompanying posterior element
      fracture with a review of literature.

PMID- 21892408
TI  - Primary extramedullary ependymoma of the cervical spine : case report and review
      of the literature.
AB  - Intradural extramedullary (IDEM) ependymomas occur very rarely and little has
      been reported about their clinical characteristics. The authors present a case of
      a 57-year-old woman with an IDEM ependymoma. She was referred for the evaluation
      of a 4-month history of increasing neck pain and muscular weakness of the left
      extremities. Magnetic resonance imaging (MRI) of the cervical spine demonstrated
      an IDEM tumor with spinal cord compression. At the time of surgery, an
      encapsulated IDEM tumor without a dural attachment or medullary infiltration was
      noted, but the tumor capsule adherent to the spinal cord and root was left in
      place to minimize the risk of neurological sequelae. Histologic examination
      revealed a benign classic ependymoma. The post-operative course was uneventful
      and radiotherapy was performed. The patient showed an excellent clinical
      recovery, with no recurrence after 5 years of follow-up.

PMID- 21892409
TI  - Unexpected seizure attack in a patient with spinal metastasis diagnosed as
      posterior reversible encephalopathy syndrome.
AB  - Seizure is a foreseeable risk in patients with brain lesion. However, seizure
      during treating non-brain lesion is not a familiar situation to neurosurgeon.
      Posterior reversible encephalopathy syndrome (PRES) is a relatively common
      situation after systemic chemotherapy. The aim of this study is to make
      neurosurgeons aware of this potential medical problem. A 52-year-old woman with
      advanced gastric cancer, presented with low back pain due to spinal metastasis at
      the 4th lumbar vertebra. Ten cycles of chemotherapy with FOLFOX (5
      Fluoruracil/Oxaliplatin) had been completed 23 days ago. Two days before the
      planned operation, a generalized tonic clonic seizure occurred. She did not have
      a history of hypertension or seizure. The seizure was stopped with lorazepam 4mg.
      The brain magnetic resonance (MR) imaging showed high signal changes in both
      parieto-occipital lobes on the T2-weighted images, and these were partially
      enhanced, suggesting PRES. The surgery was preceded by treatment with an
      antiepileptic drug. The MR images, taken 1.5 months after the seizure, showed
      that the lesion was no longer present. At 3 month follow-up, no additional
      seizure attack occurred without any seizure medication. The possibility of a
      seizure attack should be considered if the patient has a history of chemotherapy.

PMID- 21892410
TI  - A case of broncho-paraspinal fistula induced by metallic devices: delayed
      complication of thoracic spinal surgery.
AB  - We present a case report of a 45-year-old woman with spontaneous pneumocephalus
      accompanied by pneumorrhachis of the thoracic spine, which is a very rare
      condition generally associated with trauma and thoracic or spinal surgery. The
      patient had undergone an operation about 10 years earlier to treat a giant cell
      tumor of the thoracic spine. During the operation, a metallic device was
      installed, which destroyed the bronchus and caused the formation of a broncho
      paraspinal fistula. This is the suspected cause of her pneumocephalus and
      pneumorrhachis. To our knowledge, this is a very rare case of pneumocephalus
      accompanied by pneumorrhachis induced by metallic device, and when considering
      the length of time after surgery these complications presented are also
      exceptional.

PMID- 21892411
TI  - Rapid Atypical Progression of Neuro-Behcet's Disease Involving Whole Brainstem
      and Bilateral Thalami.
AB  - We present a case of Neuro-Behcet's disease with an unpredictable clinical
      course. A 47-year-old man was admitted to the neurosurgery department of our
      hospital with a mild headache. Three days after admission, his consciousness
      suddenly decreased and respiratory distress progressed rapidly. A brain MRI
      revealed that the previously observed abnormal signal had extended markedly to
      both the thalamic areas and the entire brain stem, and the surrounding brain
      parenchyma were compressed by cerebral edema. Based on the patient's symptoms of
      recurrent oral and genital ulcers, skin lesions, and uveitis, a rheumatologist
      made a diagnosis of Behcet's disease with CNS involvement. The patient was
      treated with high-dose methylprednisolone with respiratory assistance in the
      intensive care unit for 9 days and his neurologic symptoms improved remarkably.
      Neuro-Behcet's disease must be considered in the differential diagnosis in
      rapidly deteriorated young neurological patients along with a stroke, low-grade
      glioma, multiple sclerosis, and occlusive venous disease.

PMID- 21892412
TI  - Expression profiling and pathway analysis of Kruppel-like factor 4 in mouse
      embryonic fibroblasts.
AB  - BACKGROUND: Kruppel-like factor 4 (KLF4) is a zinc-finger transcription factor
      with diverse regulatory functions in proliferation, differentiation, and
      development. KLF4 also plays a role in inflammation, tumorigenesis, and
      reprogramming of somatic cells to induced pluripotent stem (iPS) cells. To gain
      insight into the mechanisms by which KLF4 regulates these processes, we conducted
      DNA microarray analyses to identify differentially expressed genes in mouse
      embryonic fibroblasts (MEFs) wild type and null for Klf4. METHODS: Expression
      profiles of fibroblasts isolated from mouse embryos wild type or null for the
      Klf4 alleles were examined by DNA microarrays. Differentially expressed genes
      were subjected to the Database for Annotation, Visualization and Integrated
      Discovery (DAVID). The microarray data were also interrogated with the Ingenuity
      Pathway Analysis (IPA) and Gene Set Enrichment Analysis (GSEA) for pathway
      identification. Results obtained from the microarray analysis were confirmed by
      Western blotting for select genes with biological relevance to determine the
      correlation between mRNA and protein levels. RESULTS: One hundred and sixty three
      up-regulated and 88 down-regulated genes were identified that demonstrated a fold
      change of at least 1.5 and a P-value < 0.05 in Klf4-null MEFs compared to wild
      type MEFs. Many of the up-regulated genes in Klf4-null MEFs encode proto
      oncogenes, growth factors, extracellular matrix, and cell cycle activators. In
      contrast, genes encoding tumor suppressors and those involved in JAK-STAT
      signaling pathways are down-regulated in Klf4-null MEFs. IPA and GSEA also
      identified various pathways that are regulated by KLF4. Lastly, Western blotting
      of select target genes confirmed the changes revealed by microarray data.
      CONCLUSIONS: These data are not only consistent with previous functional studies
      of KLF4's role in tumor suppression and somatic cell reprogramming, but also
      revealed novel target genes that mediate KLF4's functions.

PMID- 21892413
TI  - An Etiological Model for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
AB  - Kindling might represent a heuristic model for understanding the etiology of
      Myalgic Encephalomyelitis/chronic fatigue syndrome (ME/CFS). Kindling occurs when
      an organism is exposed repeatedly to an initially sub-threshold stimulus
      resulting in hypersensitivity and spontaneous seizure-like activity. Among
      patients with ME/CFS, chronically repeated low-intensity stimulation due to an
      infectious illness might cause kindling of the limbic-hypothalamic-pituitary
      axis. Kindling might also occur by high-intensity stimulation (e.g., brain
      trauma) of the limbic-hypothalamic-pituitary axis. Once this system is charged or
      kindled, it can sustain a high level of arousal with little or no external
      stimulus and eventually this could lead to hypocortisolism. Seizure activity may
      spread to adjacent structures of the limbic-hypothalamic-pituitary axis in the
      brain, which might be responsible for the varied symptoms that occur among
      patients with ME/CFS. In addition, kindling may also be responsible for high
      levels of oxidative stress, which has been found in patients with ME/CFS.

PMID- 21892414
TI  - Alzheimer's risk variants in the clusterin gene are associated with alternative
      splicing.
AB  - Genetic variation in CLU encoding clusterin has been associated with Alzheimer's
      disease (AD) through replicated genome-wide studies, but the underlying
      mechanisms remain unknown. Following earlier reports that tightly regulated CLU
      alternative transcripts have different functions, we tested CLU single nucleotide
      polymorphisms (SNPs) including those associated with AD for quantitative effects
      on individual alternative transcripts. In 190 temporal lobe samples without
      pathology we found that the risk allele of the AD associated SNP rs9331888
      increases the relative abundance of transcript NM_203339 (P=4.3*10(-12)). Using
      an independent set of 115 AD and control samples, we replicated this result
      (p=0.0014) and further observed that multiple CLU transcripts are at higher
      levels in AD compared to controls. The AD SNP rs9331888 is located in the first
      exon of NM_203339 and therefore, it is a functional candidate for the observed
      effects. We tested this hypothesis by in vitro dual luciferase assays using SK-N
      SH cells and mouse primary cortical neurons and found allelic effects on enhancer
      function, consistent with our results on post-mortem human brain. These results
      suggest a biological mechanism for the genetic association of CLU with AD risk
      and indicate that rs9331888 is one of the functional DNA variants underlying this
      association.

PMID- 21892415
TI  - Relationships among Shoplifting, Compulsive Buying, and Borderline Personality
      Symptomatology.

PMID- 21892416
TI  - The challenging and complex nature of primary health care.

PMID- 21892417
TI  - Beyond the prescription pad.

PMID- 21892418
TI  - Effectiveness of problem-solving treatment by general practice registrars for
      patients with emotional symptoms.
AB  - INTRODUCTION: In general practice many patients present with emotional symptoms.
      Both patients and physicians desire effective non-pharmacological treatments.
      AIM: To study the effectiveness of problem-solving treatment (PST) delivered by
      trained general practice registrars (GP registrars) for patients with emotional
      symptoms. METHODS: In a controlled clinical trial we compared the effectiveness
      of PST versus usual care for patients with emotional symptoms. Dutch GP
      registrars provided either PST or usual care, according to their own preference.
      Patients were included if they (a) had presented for three or more consultations
      with emotional symptoms in the past six months; and (b) scored four or more on
      the 12-item General Health Questionnaire. Outcomes at three- and nine-month
      follow-up were standard measures of depression, anxiety and quality of life.
      RESULTS: Thirty-eight GP registrars provided PST and included 98 patients; 43
      provided usual care and included 104 patients. PST patients improved
      significantly more than usual care patients: at nine-month follow-up, recovery
      rates for somatoform disorder and anxiety were higher in the PST group (OR 6.50,
      p=0.01 respectively OR 11.25, p=0.03). PST patients had improved significantly
      more on the domains social functioning, role limitation due to emotional problems
      and general health perception. DISCUSSION: Patients with emotional symptoms
      improved significantly more after PST delivered by motivated GP registrars than
      after usual care by GP registrars. Further research, with randomisation of
      interested registrars or interested GPs, is needed.

PMID- 21892419
TI  - Online access and literacy in Maori New Zealanders with diabetes.
AB  - INTRODUCTION: Online web-based interventions can be effective ancillary tools for
      managing diabetes. There is a high prevalence of diabetes in New Zealand Maori,
      and yet this group has generally been a low priority for web-based interventions
      due to perceptions of low Internet access and Internet literacy. AIM: To assess
      Internet access and literacy in New Zealanders with diabetes, especially high
      risk Maori. METHODS: A telephone survey of all patients with diabetes in an urban
      general practice. Internet access is assessed by Internet presence in the home,
      and Internet literacy by the ability to use email and the World Wide Web.
      RESULTS: One hundred percent response rate with 68 participants, including 38%
      Maori. Internet access for Maori was 70% and Internet literacy 41%. DISCUSSION:
      Internet access and literacy for Maori with diabetes may be higher than
      previously thought. Health policies may wish to focus effective and cost
      efficient web-based interventions on this high diabetes risk group.

PMID- 21892420
TI  - New Zealand health disparities-pharmacists' knowledge gaps and training needs.
AB  - INTRODUCTION: Reducing health disparities is a priority for the New Zealand (NZ)
      Government and the health care sector and, although not mandatory until 2012,
      Competence Standard 1 for NZ pharmacists has been revised to reflect this. AIM:
      The main aim was to understand the information needs of pharmacists in the
      context of reducing health inequalities in NZ through undertaking a baseline
      study of pharmacists' knowledge of health status disparities, identifying
      relevant resources most commonly read by pharmacists, soliciting ideas on how the
      profession can contribute to reducing health disparities and gauging pharmacists'
      willingness to undergo further training. METHOD: An anonymous, semi-structured
      questionnaire was posted out to 500 randomly selected practising pharmacists
      registered in NZ. RESULTS: A 27% response rate was achieved. In general,
      responding pharmacists had good health disparity knowledge about asthma and the
      prevalence of cardiovascular disease, but were less knowledgeable about
      differences in life expectancies and some mortality rates. Responding pharmacists
      made a variety of achievable suggestions where pharmacists can contribute to
      decreasing health disparities. Eighty percent of respondents indicated they were
      interested in learning more about cultural competence and health disparities in
      their community. DISCUSSION: Our results indicate a need for pharmacists to up
      skill in the area of health disparities and cultural competence and for more
      effective promotion of the resources available to pharmacists to improve their
      knowledge in this area. The pharmacists in this study appear willing to undertake
      such study; however, due to the low response rate generalisations to all
      pharmacists practising in New Zealand cannot be made.

PMID- 21892421
TI  - Disposal practices for unused medications in New Zealand community pharmacies.
AB  - INTRODUCTION: One of the recommended methods for households to dispose of unused
      medications in many countries is to return them to community pharmacies. However,
      such a practice will only reduce the environmental levels of pharmaceuticals if
      the medications are also disposed of and destroyed properly by the pharmacies.
      AIM: This study reports the results of a questionnaire sent to New Zealand
      community pharmacists regarding disposal practices for unused or expired
      medications in their workplaces. METHODS: A pre-tested, self-administered
      questionnaire was sent to 500 randomly selected community pharmacies from all
      areas of New Zealand. The participants were asked how they disposed of a variety
      of medications. In addition, participants were also asked about whether they knew
      how unused medications were destroyed if their pharmacy used a third-party
      contractor or distributor to dispose of them. RESULTS: Of the 265 respondents,
      80.4% and 61.1% respectively reported that solid and semi-solid medications were
      removed by contractors. However liquid and Class B controlled drugs were
      predominantly disposed of down the pharmacy sink. Over 60% of the participating
      pharmacists indicated that they believed the contractors incinerated the
      collected pharmaceutical waste, and over 90% of the participating pharmacists
      indicated their wish for a state-run disposal and destruction system. DISCUSSION:
      Liquid medications and Class B controlled drugs, which were commonly reported to
      be disposed of down the sewage system, may increase the potential for
      environmental pollution by pharmaceuticals in New Zealand. There is a need for
      increased environmental awareness amongst community pharmacists in New Zealand.

PMID- 21892422
TI  - Recruitment and retention of primary care patients into a research study
      investigating medication adherence.
AB  - INTRODUCTION: General practitioners (GPs) and patients are key sources of
      information for investigating primary health care. However, recruiting these into
      health care studies has been reported to be difficult. AIM: This study aimed to
      determine the recruitment and retention rates of GP practices and patients into a
      research project in the primary health care setting. METHODS: All general
      practices in Dunedin, New Zealand, with three or more practitioners were invited
      to participate in a study investigating medication adherence. In practices that
      agreed to participate, 100 patients were recruited from waiting rooms and
      followed up by telephone over six months. The main outcome measures included
      recruitment rates of GPs and patients, the level of retention and loss to follow
      up of patients over a six-month period, the drop out and reasons for this drop
      out. RESULTS: Only two of the 15 practices agreed to participate. To recruit 100
      patients, 203 people were approached. Reasons for not wanting to participate were
      recorded where possible. Of those that agreed to participate, 86% of doctor
      consultations resulted in a prescription and, of these prescriptions, 87% were
      reported to be collected as prescribed. At the end of six months, 68 patients
      still remained in the study. DISCUSSION: Patients were interested in being
      involved in this type of study and were recruited at a rate of 82% and 56%
      depending on the practice. After the initial drop out, most patients remained in
      the study until the conclusion. Recruitment of general practices remains
      challenging.

PMID- 21892423
TI  - Exploring resilience in families living with addiction.
AB  - INTRODUCTION: Information about the impact of addiction on New Zealand (NZ)
      families is scarce. A good understanding of the nature and extent of family
      problems is essential to help families become more resilient and minimise the
      consequences. This study aimed to explore experiences of NZ families living with
      addiction, identify impacts on non-addicted family members, their coping
      strategies and barriers to help seeking. METHODS: Literature and key stakeholder
      interviews informed the development of an interview schedule for 29 family
      participants recruited through health and social services. Interviews were
      recorded for analysis of central themes and critical elements that underpin
      those. Key stakeholders and informal informants were again consulted to discuss
      findings and interpretation. FINDINGS: Addiction has widespread effects on NZ
      families. The coping strategies described by the participants in this project
      lacked the positive connotations of resilience, namely positive adaptation under
      significant adversity. CONCLUSION: Family impacts of addiction are complex, and
      similar family problems arise regardless of the substance(s) involved. This small
      exploratory study indicates that the implications for NZ families deserve further
      investigation. Future research is also required to further characterise the
      impact of behavioural addictions on families, addiction in particular ethnic
      groupings and the implications of the findings for clinical practice, other
      social and health services, and for public health and social policy.

PMID- 21892424
TI  - The educational value of peer groups from a general practitioner perspective.
AB  - INTRODUCTION: Peer review groups are compulsory for New Zealand (NZ) general
      practitioners (GPs) but little is known about how they function. This study aimed
      to understand the educational value of peer group meetings to general
      practitioners and explore methods of increasing value. METHODS: A qualitative
      study was undertaken comprising a single meeting involving 22 NZ GPs with an
      interest in education and subsequent thematic analysis on the raw data. FINDINGS:
      Respondents indicated a strong belief in the educational value of peer groups.
      Pastoral care was also perceived as a valuable outcome of peer groups that was
      somewhat separate from the educational value. It would appear that the majority
      of peer groups work on the basis of internally driven contemporaneous learning
      needs based on difficult work experiences. There was limited concern over the
      wide interpretation of what constitutes acceptable topics for discussion as well
      as the informal nature of training and structuring the meetings. DISCUSSION: The
      interactive nature of peer group learning with subject matter of 'real life'
      problems would suggest peer groups have the potential to make significant change
      in the performance of doctors. A broad and differing range of experience in the
      group is more likely to generate an educationally valuable environment. It would
      appear that there may be a limited role for assisting peer groups with methods of
      structuring content and increasing effectiveness.

PMID- 21892425
TI  - Outcomes of an interdisciplinary rehabilitation programme for the management of
      chronic low back pain.
AB  - BACKGROUND AND CONTEXT: The health and economic costs associated with chronic low
      back pain (CLBP) have increased substantially over the past few decades. Despite
      extensive research, a consistently valid, reliable and effective diagnostic and
      treatment regime for CLBP is yet to be determined. ASSESSMENT OF PROBLEM: This
      paper presents an established interdisciplinary rehabilitation model for CLBP
      initially developed by the Canadian Back Institute. An audit describes the
      symptomatic, functional and vocational outcomes achieved for patients who
      attended the programme over three years throughout a national network of primary
      health care facilities in New Zealand. RESULTS: Over a three-year period, 899
      patients with CLBP completed their rehabilitation programme at one of eight
      affiliated clinics. Of the 899 patients discharged, 780 (86.8%) reported that
      their back pain had gone or reduced at the end of their rehabilitation. There was
      a statistically significant, and clinically relevant, improvement in both average
      pain and subjective functional scores from baseline assessment levels to
      discharge and follow-up scores (p<0.001). STRATEGIES FOR IMPROVEMENT: Previous
      studies have shown that functional rehabilitation can improve outcomes in
      individuals with CLBP. This audit provides further support for the development of
      interdisciplinary functional rehabilitation programmes to help manage CLBP within
      the community. LESSONS: The routine measurement of symptomatic, functional and
      vocational outcomes throughout the rehabilitation process can assist in
      quantifying the effect of treatment and providing evidence of value for patients,
      stakeholders and funding groups.

PMID- 21892427
TI  - Co-payments must go! No.

PMID- 21892426
TI  - Co-payments must go! Yes.

PMID- 21892428
TI  - Pacific SUDI and stillbirth prevention.

PMID- 21892429
TI  - Ginger--Zingiber officinale Roscoe, Zingiberaceae.

PMID- 21892430
TI  - Disclosure of genetic information to at-risk relatives: privacy law and
      professional guidance in New Zealand.

PMID- 21892431
TI  - Medicines adherence--evidence for any intervention is disappointing.
AB  - Interventions to improve adherence with medicines have been studied for many
      years. The outcomes, both for improved adherence and clinical indicators, have
      not been as positive as expected or hoped for. Any improvement in adherence that
      may occur has not necessarily translated to improved clinical outcomes. The
      studies are heterogeneous, often of poor quality, with different outcomes and
      measures of outcome, and with ill-defined interventions, such as a lack of
      information on specific content of an 'educational' intervention. It appears that
      interventions are very resource intensive with no cost-effectiveness studies.
      More research is required into interventions to improve medicines adherence
      before more health care funding is invested in labour-intensive interventions
      that appear logical but are not supported by evidence from quality research.

PMID- 21892432
TI  - Community pharmacy does not appear as part of the collaboration discourse within
      New Zealand primary care.

PMID- 21892433
TI  - An enhanced primary health care role following psychological trauma: the
      Christchurch earthquakes.
AB  - Following the February 2011 earthquake in Christchurch, New Zealand (NZ), the
      authors participated in counselling local residents, and debriefing and
      supervising support teams. Indications were that risk for mental health
      disorders, including Post-Traumatic Stress Disorder (PTSD), may be elevated in
      residents, and that this risk may continue for some time. Patients may be de
      prioritising their mental health issues when these become normalised throughout
      the city's population. The authors recommend that primary care patients are
      assessed using a brief, comprehensive tool (for example, the Case-finding and
      Help Assessment Tool) that targets many health and behavioural issues identified
      as increasing in the city following the earthquake. Anxiety and mood disorder
      symptoms may indicate assessment is appropriate to reduce harm arising from
      increased risk for PTSD. Concern also is raised for primary health care providers
      who may have experienced the trauma and additionally may be vicariously affected
      by patients' reported trauma.

PMID- 21892434
TI  - Response to the Back to back debate about the effects of shaking a baby, in the
      absence of any impact trauma.

PMID- 21892435
TI  - Response to the Back to back debate about the effects of shaking a baby, in the
      absence of any impact trauma.

PMID- 21892436
TI  - Response to the Back to back debate about the effects of shaking a baby, in the
      absence of any impact trauma.

PMID- 21892437
TI  - NZ Medical Council's position on the Four Principles.

PMID- 21892443
TI  - Tunable full-color-emitting Ca3Sc2Si3O12:Ce3+, Mn2+ phosphor via charge
      compensation and energy transfer.
AB  - A tunable full-color-emitting Ca(3)Sc(2)Si(3)O(12):Ce(3+), Mn(2+)
      (CSS:Ce(3+),Mn(2+)) phosphor is obtained by addition of doped ions as charge
      compensation. White LEDs with high R(a) (> 90) are achieved using the single
      CSS:Ce(3+),Mn(2+) phosphor.

PMID- 21892444
TI  - Oxidative properties of a nonheme Ni(II)(O2) complex: Reactivity patterns for C-H
      activation, aromatic hydroxylation and heteroatom oxidation.
AB  - Density functional theory calculations on the reactivity of a Ni(II)-superoxo
      complex in C-H bond activation, aromatic hydroxylation and heteroatom oxidation
      reactions have been explored; the Ni(II)-superoxo complex is able to react with
      substrates with weak C-H bonds and PPh(3).

PMID- 21892445
TI  - Redox reactivity of photogenerated osmium(II) complexes.
AB  - Powerful reductants [Os(II)(NH(3))(5)L](2+) (L = OH(2), CH(3)CN) can be generated
      upon ultraviolet excitation of relatively inert [Os(II)(NH(3))(5)(N(2))](2+) in
      aqueous and acetonitrile solutions. Reactions of photogenerated Os(II) complexes
      with methyl viologen to form methyl viologen radical cation and
      [Os(III)(NH(3))(5)L](3+) were monitored by transient absorption spectroscopy.
      Rate constants range from 4.9 * 10(4) M(-1) s(-1) in acetonitrile solution to 3.2
      * 10(7) (pH 3) and 2.5 * 10(8) M(-1) s(-1) (pH 12) in aqueous media.
      Photogeneration of five-coordinate Os(II) complexes opens the way for mechanistic
      investigations of activation/reduction of CO(2) and other relatively inert
      molecules.

PMID- 21892446
TI  - Modulation of an IDP binding mechanism and rates by helix propensity and non
      native interactions: association of HIF1alpha with CBP.
AB  - Intrinsically disordered proteins that acquire their three dimensional structures
      only upon binding to their targets are very important in cellular signal
      regulation. While experimental studies have been made on the structures of both
      bound (structured) and unbound (disordered) states, less is known about the
      actual folding-binding transition. Coarse grained simulations using native
      centric (i.e. Go) potentials have been particularly useful in addressing this
      problem, given the large search space for IDP binding, but have well-known
      deficiencies in reproducing the unfolded state structure and dynamics. Here, we
      investigate the interaction of HIF1alpha with CBP using a hierarchy of coarse
      grained models, in each case matching the binding affinity at 300 K to the
      experimental value. Starting from a pure Go-like model based on the native
      structure of the complex we go on to consider a more realistic model of helix
      propensity in the HIF1alpha, and finally the effect of non-native interactions
      between binding partners. We find structural disorder (i.e."fuzziness") in the
      bound state of HIF1alpha in all models which is supported by the results of
      atomistic simulations. Correcting the over-stabilized helices in the unbound
      state gives rise to a more cooperative folding-binding transition (destabilizing
      partially bound intermediates). Adding non-native contacts lowers the free energy
      barrier for binding to an almost barrierless scenario, leading to higher
      binding/unbinding rates relative to the other models, in better agreement with
      the near diffusion-limited binding rates measured experimentally. Transition
      state structures for the three models are highly disordered, supporting a fly
      casting mechanism for binding.

PMID- 21892447
TI  - Polymorphism in spin-crossover systems.
AB  - The occurrence of spin-crossover (SCO) highly depends on external influences,
      i.e. temperature, pressure, light irradiation or magnetic field, this electronic
      switching phenomenon is accompanied by drastic changes in magnetic and optical
      properties, dielectric constants, colour and structures. Thus, SCO materials are
      particularly attractive for potential applications in molecular sensing,
      switching, data storage, display, and other electronic devices at nanometric
      scale. Polymorphism is widely encountered in the studies of crystallization,
      phase transition, materials synthesis, biomineralization, and in the manufacture
      of drugs. Because different crystal forms of the same substance can possess very
      different properties and behave as different materials, so they are particularly
      meaningful for investigating SCO phenomena. Studying polymorphism of SCO
      compounds is therefore important for better understanding the structural factors
      contributing to spin transition and the structure-function relationship. This
      critical review is aimed to provide general readers with a comprehensive view of
      polymorphism in SCO systems. The article is generally structured according to
      specific metal ions and the dimensionality of compounds in the field. This paper
      is addressed to readers who are interested in multifunctional materials and
      tuning magnetic properties through supramolecular chemistry principles (129
      references).

PMID- 21892448
TI  - In situ analysis of agrochemical residues on fruit using ambient ionization on a
      handheld mass spectrometer.
AB  - We describe a rapid in situ method for detecting agrochemicals on the surface or
      in the tissue of fruit using a portable mass spectrometer equipped with an
      ambient ionization source. Two such ionization methods, low temperature plasma
      (LTP) and paper spray (PS), were employed in experiments performed at a local
      grocery store. LTP was used to detect diphenylamine (DPA) directly from the skin
      of apples in the store and those treated after harvest with DPA were recognized
      by MS and MS/MS. These data therefore allowed ready distinction between organic
      and non-organic apples. DPA was also found within the internal tissue of
      purchased apples and its distribution was mapped using LTP. Similarly,
      thiabendazole residues were detected on the skin of treated oranges in a grocery
      store experiment in which paper spray was performed by wiping the orange surface
      with a moist commercial lens wipe and then applying a high voltage to ionize the
      chemicals directly from the wipe. The handheld mass spectrometer used in these
      measurements is capable of performing several stages of tandem mass spectrometry
      (up to MS(5)); the compounds on the fruit were identified by their MS/MS
      fragmentation patterns. Protonated DPA (m/z 170) produced a characteristic MS(2)
      fragment ion at m/z 92, while thiabendazole was identified by MS(3) using
      precursor to fragment ion transitions m/z 202 ->m/z 175 ->m/z 131. These
      particular examples exemplify the power of in situ analysis of complex samples
      using ambient ionization and handheld mass spectrometers.

PMID- 21892449
TI  - A graphene oxide-peptide fluorescence sensor tailor-made for simple and sensitive
      detection of matrix metalloproteinase 2.
AB  - A graphene oxide-peptide based fluorescence sensor has been developed for matrix
      metalloproteinase 2 (MMP2), and its applicability has been demonstrated by
      monitoring the concentration of MMP2 secreted by HeLa cells, revealing that HeLa
      cells with a density of 5.48 * 10(5) cells per mL can produce 22 nM in cell
      culture media in 24 h.

PMID- 21892450
TI  - Thienopyrrolyl dione end-capped oligothiophene ambipolar semiconductors for thin
      film- and light emitting transistors.
AB  - The design, synthesis and structure-property investigation of a new
      thienopyrrolyl dione substituted oligothiophene material showing reduced band gap
      energy, low lying LUMO energy level and ambipolar semiconducting behaviour is
      described.

PMID- 21892452
TI  - Preface for the themed issue of Chemical Society Reviews.

PMID- 21892451
TI  - A Mn(III)-superoxo complex of a zwitterionic calix[4]arene with an unprecedented
      linear end-on Mn(III)-O2 arrangement and good catalytic performance for alkene
      epoxidation.
AB  - Reactions of [H(4)L][PF(6)](4) with 4 equiv. of Mn(OAc)(2).4H(2)O in the presence
      of air gave rise to a mononuclear Mn(III)-superoxo complex
      [Mn(III)L(O(2))(H(2)O)](PF(6))(2), which contains a bowl-shaped cationic
      structure with a D(4d) symmetry. It has an unprecedented linear end-on Mn(III)
      O(2) unit and exhibited good efficiency and selectivity in the catalytic
      oxidation of alkenes with O(2) plus isobutyraldehyde under mild conditions.

PMID- 21892453
TI  - Exploring the potential of the beta-thiolactones in bioorganic chemistry.
AB  - A series of novel peptide-based beta-thiolactones were synthesized and assayed
      for cytotoxicity against several human cancer cell lines, where they showed
      greater activity than the corresponding beta-lactones and beta-lactams. Several
      of the beta-thiolactones prepared showed strong inhibitory activity in vitro
      against human cathepsins B and L.

PMID- 21892454
TI  - Highly sensitive electrical detection of TCNE on chemically passivated silicon-on
      insulator.
AB  - Adsorption of tetracyanoethylene (TCNE) onto hydrogen terminated, n-type silicon
      on-insulator is shown to cause significant depletion of majority carriers.
      Employing an ambient pseudo-MOSFET, ppm levels of TCNE vapour rapidly decrease
      the n-channel saturation current by at least two orders of magnitude. Covalent
      passivation with a decyl monolayer improves the reversibility of the response
      while only slightly decreasing the sensitivity.

PMID- 21892455
TI  - One-pot synthesis of hybrid TiO2-polyaniline nanoparticles by self-catalyzed
      hydroamination and oxidative polymerization from TiO2-methacrylic acid
      nanoparticles.
AB  - A simple self-catalyzed hydroamination method for creating hybrid TiO(2)
      polyaniline core-shell nanoparticles (NP) has been shown. Hybrid NPs with a range
      of possible sizes are afforded in high yield under mild reaction conditions and
      simultaneously show improved charge transport and electrochromic behavior
      compared to either polyaniline alone or physically blended with TiO(2).

PMID- 21892456
TI  - 13C-NMR quantification of proton exchange at LewisX hydroxyl groups in water.
AB  - NMR-based analysis of glycans by directly observing hydroxyl protons has been
      difficult because of their inherently fast exchange with water. We observed
      hydroxyl proton exchanges in a LewisX-LewisX interaction by using deuterium
      isotope shifts on (13)C-NMR. This strategy is suitable for analyzing weak
      interactions by identifying involved protons.

PMID- 21892457
TI  - Reverse orthogonal strategy for oligosaccharide synthesis.
AB  - Herein, we report the invention of a novel expeditious concept for
      oligosaccharide synthesis. Unlike the classic orthogonal strategy based on
      leaving groups, the reverse approach is based on orthogonal protecting groups,
      herein p-methoxybenzyl and 4-pentenoyl, which allows for efficient
      oligosaccharide assembly in the reverse direction.

PMID- 21892458
TI  - Selective Diels-Alder cycloaddition on semiconducting single-walled carbon
      nanotubes for potential separation application.
AB  - Selectivity for the Diels-Alder cycloaddition reaction of the electron-rich diene
      with single-walled carbon nanotubes was first investigated. This chemistry is a
      complete departure from the curvature-dependent reactivity based on the carbon
      pyramidalization angle.

PMID- 21892459
TI  - Twisted molecular magnets.
AB  - The use of derivatised salicylaldoximes in manganese chemistry has led to the
      synthesis of a family of approximately fifty hexanuclear ([Mn(III)(6)]) and
      thirty trinuclear ([Mn(III)(3)]) Single-Molecule Magnets (SMMs). Deliberate,
      targeted structural distortion of the metallic core afforded family members with
      increasingly puckered configurations, leading to a switch in the pairwise
      magnetic exchange from antiferromagnetic to ferromagnetic. Examination of both
      the structural and magnetic data revealed a semi-quantitative magneto-structural
      correlation, from which the factors governing the magnetic properties could be
      extracted and used for predicting the properties of new family members and even
      more complicated structures containing analogous building blocks. Herein we
      describe an overview of this extensive body of work and discuss its potential
      impact on similar systems.

PMID- 21892460
TI  - A novel pH-sensitive (+/-)-alpha-tocopherol-5-fluorouracil adduct with
      antioxidant and anticancer properties.
AB  - A novel pH-sensitive (+/-)-alpha-tocopherol-5-fluorouracil (VE-5-FU) adduct with
      antioxidant and anticancer properties for antioxidant-based cancer
      chemoprevention was synthesized and utilized for selective drug release in the
      stomach.

PMID- 21892461
TI  - Reducing the conformational flexibility of carbohydrates: locking the 6-hydroxyl
      group by cyclopropanes.
AB  - The 6-hydroxyl group of hexopyranosides was stereochemically locked by the
      spiroannelation of a cyclopropane unit at C-5. The corresponding glucose and
      mannose derivatives were prepared and their behaviour in glycosidation reactions
      was studied.

PMID- 21892462
TI  - Hydrogen-bond driven assembly of a molecular capsule facilitated by
      supramolecular chelation.
AB  - Resorcinarene-based cavitands functionalized with acetamido groups capable of
      self-complementary hydrogen-bond interactions, were synthesized in order to
      construct supramolecular capsules. The 1,3-bifunctionalized cavitand produced a
      polymeric assembly, whereas the tetra-functionalized analogue yielded a discrete
      capsule held together via N-H...O hydrogen bonds. The ethynyl species attached to
      the rim of these host molecules deepen each cavitand and expands the volume of
      the resulting capsule.

PMID- 21892463
TI  - Titanium nitride catalyst cathode in a Li-air fuel cell with an acidic aqueous
      solution.
AB  - TiN was used as an oxygen reduction reaction (ORR) catalyst in a Li-air fuel cell
      with a non-aqueous/acidic aqueous hybrid electrolyte. The electrochemical
      properties of the TiN based catalyst and the single cell were extensively
      investigated. It is suggested that TiN has considerable electrochemical catalytic
      activity for Li-air fuel cells in a weak acidic solution.

PMID- 21892464
TI  - Palladium nanoparticles in carbon thin film-lined SBA-15 nanoreactors: efficient
      heterogeneous catalysts for Suzuki-Miyaura cross coupling reaction in aqueous
      media.
AB  - Embedding Pd nanoparticles in carbon thin film-lined SBA-15 nanoreactors provides
      highly efficient catalysts for heterogeneous cross coupling reactions in aqueous
      media. No leaching or aggregation of Pd nanoparticles was found in these
      nanoreactors after reusing them several times. The carbon thin film lining of
      these nanoreactors was further confirmed with small molecular arene probing
      experiments.

PMID- 21892465
TI  - Thioflavin T forms a non-fluorescent complex with alpha-helical poly-L-glutamic
      acid.
AB  - Thioflavin T (ThT) is a molecular-rotor-type fluorophore reputed for the
      selective binding to amyloid fibrils. Using induced circular dichroism, here we
      show that ThT binds in an orderly manner to alpha-helical poly-L-glutamic acid
      (PLGA) implying that neither stacked beta-sheets nor pi-pi stacking interactions
      are necessary for the binding between the dye and proteins.

PMID- 21892466
TI  - Chemical and light triggering of peptide networks under partial thermodynamic
      control.
AB  - The kinetics of novel dynamic libraries that operate via reversible replication
      is described. In these systems, selective product formation is governed by
      peptides autocatalytic efficiency and by differences in their unfolding
      stability. We suggest ways to significantly alter the network behavior by
      chemical inputs (templates) or physical triggers (light).

PMID- 21892467
TI  - syn-Selective asymmetric cross-aldol reactions between aldehydes and glyoxylic
      acid derivatives catalyzed by an axially chiral amino sulfonamide.
AB  - syn-Selective asymmetric cross-aldol reactions of aldehydes with tert-butyl
      glyoxylate and glyoxamide were realized by the use of an axially chiral amino
      sulfonamide (S)-1. The cross-aldol products obtained are densely functionalized
      and readily converted to synthetically useful and important chiral building
      blocks such as gamma-lactone and gamma-lactam.

PMID- 21892468
TI  - Luminescence on-off switching via reversible interconversion between inter- and
      intramolecular aurophilic interactions.
AB  - Reversible interconversion between inter- and intramolecular AuAu interactions
      induces luminescence on/off switching in solid state. For the gold(I)
      photoluminescence system, intermolecular aurophilic interaction is a more
      significant factor than intramolecular aurophilic interaction.

PMID- 21892469
TI  - Enhancement of visible light photocatalysis by grafting ZnO nanoplatelets with
      exposed (0001) facets onto a hierarchical substrate.
AB  - A ZnO nanocatalyst with a high percentage exposure of (0001) facets embedded on a
      hierarchical flower-like matrix has been prepared by an in situ topotactic
      transformation of a layered double hydroxide precursor, and exhibits
      significantly higher visible light photocatalytic performance than other ZnO
      nanomaterials with fewer exposed (0001) facets.

PMID- 21892470
TI  - Early-late heterobimetallic Rh-Ti and Rh-Zr complexes via addition of early metal
      chlorides to mono- and divalent rhodium.
AB  - Addition of TiCl(4) or ZrCl(4) to (PNP)Rh(CH(2)==CH(t)Bu) (1) rapidly gives
      complexes (PNP)Rh(MCl(3))(Cl) (M = Ti, 2; Zr, 3) in 75-77% yield (PNP = (4-Me-2
      ((i)Pr(2)P)-C(6)H(3))(2)N). Compound 2 can also be synthesized via a reaction of
      (PNP)RhCl with TiCl(3) or of (PNP)TiCl(3) with 1/2 [(cod)RhCl](2).

PMID- 21892471
TI  - Ancillary nitrile substituents as convenient IR spectroscopic reporters for self
      assembly of mercapto- and isocyanoazulenes on Au(111).
AB  - Synthesis and self-assembly of structurally related mercapto- and
      isocyanoazulenes, including novel 2-mercapto-1,3-dicyanoazulene (4) and 2
      isocyano-1,3-dicyanoazulene (5), are reported. Exposing 5 adsorbed on Au(111) to
      a solution of 4 displaces the isocyanoazulene monolayer with that of the
      mercaptoazulene as judged by nu(C=N) signatures of these films.

PMID- 21892472
TI  - A molecular Mo4Bi4 framework composed exclusively of unsupported metal-metal
      bonds.
AB  - Reaction of [Cp(2)MoH(2)] with bismuth allyloxide, [Bi{OCH(CH(3))CH==CH(2)}(3)],
      gave rise to an extended octanuclear complex wherein two cyclic Mo(2)Bi(2) units
      composed of four Mo-Bi bonds are linked by a Bi-Bi bond. The fact that the
      construction of such an assembly could be accomplished only in the case of a
      monomethylation of the parent allyl residue demonstrates a subtle substituent
      effect.

PMID- 21892473
TI  - Intercalation and grafting of benzene derivatives into zinc-aluminum and copper
      chromium layered double hydroxide hosts: an XPS monitoring study.
AB  - We report an original strategy to describe, via X-ray photoelectron spectroscopy
      (XPS) measurements, the interactions between the organic and the mineral sub
      systems within a multifunctional hybrid material. A tunable layered double
      hydroxide (LDH) host system, either a Zn(2)Al- or Cu(2)Cr-hydrotalcite like
      compound, is modified with the insertion of the organic guest entities, 4-phenol
      sulfonate (HBS) or -carboxylate (HBC). The resulting interactions are studied at
      two levels: after the organic molecules' insertion in the host LDH (ionic
      exchange between the LDH counter-ions and the organic anions) and after the
      condensation (grafting) of the organic species onto the mineral layers when
      thermally treated. For the inserted material, the main XPS results show a
      stabilization of the organic molecules within the mineral sheets via H bonding as
      found elsewhere with FTIR study, the mineral matrix being unchanged. The XPS
      signal of the organic molecules slightly changes with a widening of core peaks,
      attesting to some local surrounding modifications. When heating up the Zn(2)Al
      hybrid material, stronger interactions between organic and inorganic systems
      appeared from around 80  degrees C with some obvious electronic changes as
      monitored with the XPS S2p signal of the HBS guest molecules. At the same time,
      the PXRD pattern clearly shows a decrease of the basal spacing according to a two
      step contraction process which could be interpreted as a progressive organic
      molecule condensation onto the inorganic layers via iono-covalent bonds. A copper
      chromium LDH is also studied to probe the same kind of interactions with the HBS
      molecules. The ability of distortion of such mineral material involves a peculiar
      process of contraction from 40  degrees C with the immediate and effective
      anchorage of organic molecules.

PMID- 21892474
TI  - Interaction strength between proteins and polyelectrolyte brushes: a small angle
      X-ray scattering study.
AB  - We present an investigation of beta-lactoglobulin adsorption onto spherical
      polyelectrolyte brushes (SPBs) by small angle X-ray scattering (SAXS). The SPB
      consists of a polystyrene core onto which long chains of poly(styrene sulfonate)
      are grafted. The amount and the distribution of proteins adsorbed in the brush
      layer at low ionic strength can be derived from SAXS. The analysis of the SAXS
      data reveals additionally that some of the protein molecules form aggregates of
      about six monomers in the adsorbed state. Furthermore, the position and the
      amount of slightly bound protein can be detected by the combination of the SAXS
      results and the SPB loading after extensive ultrafiltration. The total amount of
      adsorbed protein is compared to data derived from isothermal titration
      calorimetry. The comparison of both sets of data demonstrates that the protein
      molecules in the inner layers of the spherical polyelectrolyte brush are firmly
      bound. Proteins located in the outer layers are only weakly bound and can be
      washed out by prolonged ultrafiltration.

PMID- 21892475
TI  - Electron solvation and solvation-induced crystallization of an ammonia film on
      Ag(111) studied by 2-photon photoemission.
AB  - Intermolecular interaction plays a crucial role in electron solvation in the
      condensed phase. Here, we present a femtosecond time-resolved and angle-resolved
      2-photon photoemission (2PPE) study on the dynamics of electron solvation in a 2
      dimensional ammonia film on a metal substrate. While the weakly chemisorbed first
      monolayer (ML) supports delocalized image-potential (IP) states that resemble
      those of the bare Ag(111) substrate, an additional monolayer localizes the IP
      state with a larger binding energy obtained through a pre-solvation process.
      Structural disorder in the metastable ammonia films (>2 ML) leads to a prominent
      photoelectron peak that is attributed to the long-lived trapped electron state
      (e(T)) located at 1.5 eV above the Fermi level. Photoinduced crystallization of
      the metastable phase, verified by the recovery of a delocalized IP state, is
      suggested to result from inelastic scattering between interfacial electrons and
      disordered ammonia molecules.

PMID- 21892476
TI  - Molecular dynamics effects on luminescence properties of oligothiophene
      derivatives: a molecular mechanics-response theory study based on the CHARMM
      force field and density functional theory.
AB  - CHARMM force field parameter values for a class of oligothiophene derivatives
      have been derived with reference to density functional theory/B3LYP potential
      energy surfaces. The force field parametrization of these luminescent conjugated
      polyelectrolytes includes the electronic ground state as well as the strongly
      light absorbing first excited state. In conjunction with quantum chemical
      response theory calculations of transition state properties, a molecular
      dynamical model of the Stokes shift is obtained. The theoretical model is
      benchmarked against experimental data recorded at room temperature which refer to
      sodium salts of p-HTAA and p-FTAA with distilled water as a solvent. For p-HTAA
      the theoretically predicted Stokes shift of 112 nm is in good agreement with the
      experimental result of 124 nm, given the approximations about exciton
      localization that were introduced to obtain a force field for the excited state.

PMID- 21892477
TI  - Association of ionic liquids in solution: a combined dielectric and conductivity
      study of [bmim][Cl] in water and in acetonitrile.
AB  - Ion association of the ionic liquid [bmim][Cl] in acetonitrile and in water was
      studied by dielectric spectroscopy for salt concentrations c <= 1.3 M at 298.15 K
      and by measurement of molar electrical conductivities, Lambda, of dilute
      solutions (c <= 0.006 M) in the temperature range 273.15 ? T/K <= 313.15. Whilst
      acetonitrile solutions of [bmim][Cl] exhibit moderate ion pairing, with an
      association constant of K degrees (A) ~ 60 M(-1) and increasing with temperature,
      [bmim][Cl] is only weakly associated in water (K degrees (A) ~ 6 M(-1)) and ion
      pairing decreases with rising temperature. Only contact ion pairs were detected
      in both solvents. Standard-state enthalpy, entropy and heat capacity changes of
      ion association were derived, as well as the activation enthalpy of charge
      transport and the limiting conductivity of the cation, lambda(infinity)
      ([bmim](+)). These data, in conjunction with effective solvation numbers obtained
      from the dielectric spectra, suggest that the solvation of [bmim](+) is much
      weaker in water than in acetonitrile.

PMID- 21892478
TI  - Double template effect in [4 + 4] Schiff base macrocycle formation; an ESI-MS
      study.
AB  - The mechanism of self-assembly of a polynuclear complex of a [4 + 4] Schiff base
      iminomethylenediphenolate macrocycle [BaCu(4)(4 + 4)](2+) via a non-macrocyclic
      dialdehyde intermediate has been followed using ESI-MS of the reaction solutions.
      Both assembly of the intermediate and Schiff-base condensation with diamine give
      rise to single products; formation of the intermediate metallacycle is fast but
      Schiff-base condensation is much slower. Both intermediate complex and
      macrocyclic product have been structurally characterised.

PMID- 21892479
TI  - Spatiotemporal classification of environmental monitoring data in the Yeongsan
      River basin, Korea, using self-organizing maps.
AB  - Environmental monitoring data for planning, implementing and evaluating the Total
      Maximum Daily Loads (TMDL) management system have been measured at about 8-day
      intervals in a number of rivers in Korea since 2004. In the present study, water
      quality parameters such as Suspended Solids (SS), Biochemical Oxygen Demand
      (BOD), Dissolved Oxygen (DO), Total Nitrogen (TN), and Total Phosphorus (TP) and
      the corresponding runoff were collected from six stations in the Yeongsan River
      basin for six years and transformed into monthly mean values. With the primary
      objective to understand spatiotemporal characteristics of the data, a
      methodologically systematic application of a Self-Organizing Map (SOM) was made.
      The SOM application classified the environmental monitoring data into nine
      clusters showing exclusively distinguishable patterns. Data frequency at each
      station on a monthly basis identified the spatiotemporal distribution for the
      first time in the study area. Consequently, the SOM application provided useful
      information that the sub-basin containing a metropolitan city is associated with
      deteriorating water quality and should be monitored and managed carefully during
      spring and summer for water quality improvement in the river basin.

PMID- 21892480
TI  - Improving suspended sediment measurements by automatic samplers.
AB  - Suspended solids either as total suspended solids (TSS) or suspended sediment
      concentration (SSC) is an integral particulate water quality parameter that is
      important in assessing particle-bound contaminants. At present, nearly all
      stormwater runoff quality monitoring is performed with automatic samplers in
      which the sampling intake is typically installed at the bottom of a storm sewer
      or channel. This method of sampling often results in a less accurate measurement
      of suspended sediment and associated pollutants due to the vertical variation in
      particle concentration caused by particle settling. In this study, the
      inaccuracies associated with sampling by conventional intakes for automatic
      samplers have been verified by testing with known suspended sediment
      concentrations and known particle sizes ranging from approximately 20 MUm to 355
      MUm under various flow rates. Experimental results show that, for samples
      collected at a typical automatic sampler intake position, the ratio of sampled to
      feed suspended sediment concentration is up to 6600% without an intake strainer
      and up to 300% with a strainer. When the sampling intake is modified with
      multiple sampling tubes and fitted with a wing to provide lift (winged arm
      sampler intake), the accuracy of sampling improves substantially. With this
      modification, the differences between sampled and feed suspended sediment
      concentration were more consistent and the sampled to feed concentration ratio
      was accurate to within 10% for particle sizes up to 250 MUm.

PMID- 21892481
TI  - Rounded multi-level microchannels with orifices made in one exposure enable
      aqueous two-phase system droplet microfluidics.
AB  - Exposure of a negative photoresist-coated glass slide with diffused light from
      the backside through a mask with disconnected features provides multi-level
      rounded channels with narrow orifices in one exposure. Using these structures, we
      construct microfluidic systems capable of creating aqueous two-phase system
      droplets where one aqueous phase forms droplets and the other aqueous phase forms
      the surrounding matrix. Unlike water-in-oil droplet systems, aqueous two-phase
      systems can have very low interfacial tensions that prevent spontaneous droplet
      formation. The multi-level channels fabricated by backside lithography satisfy
      two conflicting needs: (i) the requirement to have narrowed channels for
      efficient valve closure by channel deformation and (ii) the need to have wide
      channels to reduce the flow velocity, thus reducing the capillary number and
      enhancing droplet formation.

PMID- 21892483
TI  - Rhenium-catalyzed allylation of C-H bonds of benzoic and acrylic acids.
AB  - We have succeeded in the allylation of aromatic and olefinic C-H bonds of benzoic
      and acrylic acids using a rhenium catalyst, Re(2)(CO)(10). In this reaction,
      isomerization of the introduced allyl group to the 1-propenyl group did not
      occur.

PMID- 21892484
TI  - Iridium(III) soft salts from dinuclear cationic and mononuclear anionic complexes
      for OLED devices.
AB  - Two iridium(III) soft salts based on ion-paired dinuclear cationic and
      mononuclear anionic complexes were designed and investigated as phosphorescent
      emitters for solution processed OLEDs. New dinuclear cationic complexes were
      prepared with two different bridging ligands, a carbazole and a phenylene spacer.
      Best devices were designed with the soft salt bearing a carbazole moiety.

PMID- 21892485
TI  - One-pot synthesis of luminol functionalized silver nanoparticles with
      chemiluminescence activity for ultrasensitive DNA sensing.
AB  - A novel one-pot method for the synthesis of chemiluminescence functionalized
      AgNPs has been reported and an ECL sensor has been developed for the detection of
      M. tuberculosis DNA.

PMID- 21892486
TI  - Spin-label ESR with nanochannels to improve the study of backbone dynamics and
      structural conformations of polypeptides.
AB  - Nanochannels of mesoporous silica materials were previously found useful for
      reducing the tumbling motion of encapsulated biomolecules while leaving the
      biomolecular structure undisturbed. Here we show that experiments of cw-ESR
      distance measurement in nano-confinement can benefit immediately from the above
      mentioned features of sufficiently slow molecular tumbling, enabling more
      accurate determination of interspin distances throughout the temperature range,
      from 200 to 300 K. A 26-residue prion protein peptide, which can fold into either
      a helical or hairpin structure, as well as its variants, are studied by using
      ESR. By comparing the spectra obtained in vitrified bulk solutions vs. mesopores,
      the spectra from the latter display typical slow-motional lineshapes, thereby
      enabling dipolar anisotropy to be unambiguously revealed throughout the
      temperature range, whereas the spectra from the former are dominated by the
      disordering of the side chain and the rotational tumbling of the peptide. The
      spectral changes regarding the two secondary structures in nano-confinement are
      found to show a strong correlation with the dynamic properties of the backbones.
      The effect of viscosity agent perturbation on the motion of an R1 nitroxide side
      chain, a commonly employed probe, could be substantial in a bulk solution
      condition, though it is absolutely absent in nanochannels. Under nano
      confinement, the probe is proven sufficiently sensitive to the backbone motions.
      Overall, the distance distributions determined from the mesopore studies not only
      describe the conformational structures (by average distances), but also the
      backbone dynamics (by distribution widths) of the spin-labeled peptides.

PMID- 21892487
TI  - Quantitative analysis of energy transfer between fluorescent proteins in CFP-GBP
      YFP and its response to Ca2+.
AB  - This article reports the full characterisation of the optical properties of a
      biosynthesised protein consisting of fused cyan fluorescent protein, glucose
      binding protein and yellow fluorescent protein. The cyan and yellow fluorescent
      proteins act as donors and acceptors for intramolecular fluorescence resonance
      energy transfer. Absorption, fluorescence, excitation and fluorescence decays of
      the compound protein were measured and compared with those of free fluorescent
      proteins. Signatures of energy transfer were identified in the spectral
      intensities and fluorescence decays. A model describing the fluorescence
      properties including energy transfer in terms of rate equations is presented and
      all relevant parameters are extracted from the measurements. The compound protein
      changes conformation on binding with calcium ions. This is reflected in a change
      of energy transfer efficiency between the fluorescent proteins. We track the
      conformational change and the kinetics of the calcium binding reaction from
      fluorescence intensity and decay measurements and interpret the results in light
      of the rate equation model. This visualisation of change in protein conformation
      has the potential to serve as an analytical tool in the study of protein
      structure changes in real time, in the development of biosensor proteins and in
      characterizing protein-drug interactions.

PMID- 21892488
TI  - Time-dependent intermolecular interaction during protein reactions.
AB  - A recently developed method to monitor reaction kinetics of intermolecular
      interaction is presented in this perspective. This method is based on time
      dependent diffusion coefficient measurements using the pulsed laser induced
      transient grating technique. Using this method, time dependent biomolecular
      interactions, such as transient association and dissociation reactions in
      solution, have been successfully detected in real time. The principles and
      particular applications are described. In particular, unique features of this
      time-dependent diffusion coefficient method are emphasized by comparison with
      other techniques.

PMID- 21892489
TI  - On the PES for the interaction of an H atom with an H chemisorbate on a graphenic
      platelet.
AB  - Motivated by the problem of H(2) formation in diffuse clouds of the interstellar
      medium (ISM), we study the effect of including van der Waals-type corrections in
      DFT calculations on the entrance PES of the Eley-Rideal reaction H(b) + H(a)-GR 
      > H(b)-H(a) + GR for a graphenic surface GR. The present calculations make use of
      the PBE-D3 dispersion corrected functional of Grimme et al. (2010) and are
      carried out on cluster models of graphenic surfaces: C(24)H(12) and C(54)H(18).
      To assess the soundness of the chosen functional we start by revisiting the H-GR
      adsorption potential. We find a satisfactory on top physisorption well (43-48
      meV) correctly located at an H-GR distance of 3 A. We then revisit the H(b)-H(a)
      GR system using both the PW91 and PBE functionals. Our calculations do not
      reproduce the tiny potential barrier reported earlier for large H(b)distances
      from the surface. The barrier in the calculations of Sidis et al. (2000) and
      Morisset et al. (2003, 2004) has been traced to their previous use of an LSDA +
      POSTSCF PW91 procedure rather than the genuine PW91 one. The new PBE-D3 PES for
      the H(b)-H(a)-GR system is reported as a function of the H(b) distance to the
      surface and its impact parameter relative to the H(a) chemisorbate for the so
      called "fixed puckered" ("diabatic" or "sudden") approach. The results are
      discussed in relation to recent experimental and theoretical work.

PMID- 21892490
TI  - Lipidology and lipidomics--quo vadis? A new era for the physical chemistry of
      lipids.
AB  - Our picture of lipid membranes has come a long way since Gorter and Grendel in
      1925 formulated the lipid bilayer hypothesis. Most modern textbook models of
      membranes are based on the Singer-Nicolson model from 1972, although we have in
      recent years seen significant amendments to this model, not least fuelled by the
      finding of lipid membrane domains and the subsequent 'raft rush'. The science of
      lipids, lipidology, has now become an established discipline, acknowledging that
      lipids organize in space and time and display emergent physico-chemical
      properties that are beyond the chemical nature of the individual molecules and
      which collectively control membrane function. Recently, lipidomics has been
      followed as a new discipline in the omics-sequel, characterized by an explosion
      in detailed data for lipid profiles of tissues, cells, and subcellular
      components. The focus is now swinging toward enumerating individual lipid
      species, determining their identity, and quantitating their amount. Time is ripe
      to marry the two disciplines, both in order to take lipidomics beyond the stage
      of 'stamp collection' and in order to incorporate into the lipidology approach
      the new knowledge about the individual lipid species. As an important matchmaker
      for this marriage, the physical chemistry of lipids in lipid bilayers and
      membranes is entering a new era of renaissance.

PMID- 21892491
TI  - Studies of the reactions of tripodal pyridine-containing ligands with Re(CO)5Br
      leading to rheniumtricarbonyl complexes with potential biomedical applications.
AB  - The complexes formed from the reaction of N-acylated tris-(pyridin-2
      yl)methylamine (LH) with [Re(CO)(5)Br] depend on the structure of the ligand and
      the reaction conditions. Thus, while N-[1,1,1-tris-(pyridin-2-yl)methyl]acetamide
      coordinates through the three pyridine nitrogens to give a stable cationic
      complex [LHRe(CO)(3)Br], the analogous N-benzoyl ligand reacts under similar
      conditions to give a neutral complex [LRe(CO)(3)] with coordination through two
      pyridine nitrogens and a deprotonated amide. To try to explain these different
      outcomes, the reactions of some structurally related N-acylated [1,1-bis(pyridin
      2-yl)]methylamines (L'H) with [Re(CO)(5)Br] have been studied and the reaction
      pathways identified. These studies indicate that a neutral complex
      [L'HRe(CO)(3)Br] is initially formed in which the amide portion of the ligand is
      uncoordinated, but that this complex under appropriate conditions then rearranges
      to give a cationic complex [L'HRe(CO)(3)]Br in which the coordinated amide
      nitrogen either remains protonated or is present in its imidic acid tautomeric
      form. Elimination of HBr from these complexes either thermally or in the presence
      of base then gives stable neutral complexes [L'Re(CO)(3)]. The impact of the N
      acyl group and any substituent at the apex of the tripodal ligands (L''H) on the
      relative stabilities of intermediate complexes on the reaction pathway helps
      provide an explanation for the observed difference in behaviour of the N-acylated
      tris(pyridin-2-yl)methylamines (LH).

PMID- 21892492
TI  - Mesoporous silica nanoparticles loading doxorubicin reverse multidrug resistance:
      performance and mechanism.
AB  - Multidrug resistance (MDR) is one of the major obstacles for successful
      chemotherapy in cancer. One of the effective approaches to overcome MDR is to use
      nanoparticle-mediated drug delivery to increase drug accumulation in drug
      resistant cancer cells. In this work, we first report that the performance and
      mechanism of an inorganic engineered delivery system based on mesoporous silica
      nanoparticles (MSNs) loading doxorubicin (DMNs) to overcome the MDR of MCF-7/ADR
      (a DOX-resistant and P-glycoprotein (P-gp) over-expression cancer cell line). The
      experimental results showed that DMNs could enhance the cellular uptake of
      doxorubicin (DOX) and increase the cell proliferation suppression effect of DOX
      against MCF-7/ADR cells. The IC(50) of DMNs against MCF-7/ADR cells was 8-fold
      lower than that of free DOX. However, an improved effect of DOX in DMNs against
      MCF-7 cells (a DOX-sensitive cancer cell line) was not found. The increased
      cellular uptake and nuclear accumulation of DOX delivered by DMNs in MCF-7/ADR
      cells was confirmed by confocal laser scanning microscopy, and could result from
      the down-regulation of P-gp and bypassing the efflux action by MSNs themselves.
      The cellular uptake mechanism of DMNs indicated that the macropinocytosis was one
      of the pathways for the uptake of DMNs by MCF-7/ADR cells. The in vivo
      biodistribution showed that DMNs induced a higher accumulation of DOX in drug
      resistant tumors than free DOX. These results suggested that MSNs could be an
      effective delivery system to overcome multidrug resistance.

PMID- 21892493
TI  - Silica nanoparticles functionalised with cation coordination sites and
      fluorophores for the differential sensing of anions in a quencher displacement
      assay (QDA).
AB  - In conjunction with quenching metal ions, silica nanoparticles carrying
      terpyridine coordination sites and sulforhodamine B signalling units were
      employed for the differential fluorometric recognition of anions.

PMID- 21892494
TI  - Precise engineering and visualization of signs and magnitudes of DNA writhe on
      the basis of PNA invasion.
AB  - It is demonstrated that the right and left handedness of DNA supercoils can be
      engineered precisely and readily at the molecular level in vitro through
      utilization of the invading property of peptide nucleic acid.

PMID- 21892495
TI  - Homoleptic tris(methoxydimethylsilyl)silanides of the alkaline earth metals:
      first zwitterionic silanides with two naked silyl anions.
AB  - The first zwitterionic alkaline earth metal silanides featuring two naked silyl
      anions were synthesized and a combined structural and computational study on
      these zwitterions revealed a correlation between the energy of the HOMO and the
      degree of negative charge of the naked silyl anions.

PMID- 21892496
TI  - Direct electronic communication at bio-interfaces assisted by layered-metal
      hydroxide slab arrays with controlled nano-micro structures.
AB  - The electronic transfer (eT) at bio-interfaces has been achieved by orientating
      2D inorganic slabs in a regular arrangement with the slab ab-planes vertical to
      the electrode substrate. The eT rate is effectively promoted by tuning the nano
      micro scale structures of perpendicular LDH arrays.

PMID- 21892497
TI  - Facile synthesis of thermosensitive magnetic nanoparticles as "smart" draw
      solutes in forward osmosis.
AB  - Thermosensitive superparamagnetic nanoparticles were synthesized by a one-step
      thermal decomposition method and successfully recycled as a 'smart' draw solute
      in forward osmosis processes for water reuse without losing performance
      efficiency.

PMID- 21892498
TI  - A gram scale synthesis of a multi-13C-labelled anthocyanin, [6,8,10,3',5'
      13C5]cyanidin-3-glucoside, for use in oral tracer studies in humans.
AB  - The major dietary anthocyanin, cyanidin-3-glucoside, was prepared on a 4 g scale
      from three units of diethyl [2-(13)C]malonate and one unit of [1,3
      (13)C(2)]acetone, such that five isotope locations were distributed throughout
      the molecule to provide a penta-(13)C(5)-labelled anthocyanin, [6,8,10,3',5'
      (13)C(5)]cyanidin-3-glucoside chloride, for use in human stable-isotope tracer
      studies.

PMID- 21892499
TI  - Use of alkyl 2,4,6-triisopropylbenzoates in the asymmetric homologation of
      challenging boronic esters.
AB  - (-)-Sparteine induced lithiation of primary 2,4,6-triisopropylbenzoates and
      subsequent homologation of boronic esters is reported. A comparative study with
      lithiated N,N-diisopropylcarbamates has demonstrated the superiority of the
      hindered benzoate.

PMID- 21892501
TI  - Asymmetric Bronsted acid catalyzed carbonyl activation--organocatalytic domino
      electrocyclization-halogenation reaction.
AB  - A highly efficient Bronsted acid catalyzed enantioselective Nazarov cyclization
      bromination reaction has been developed. The protocol gives access to highly
      functionalized trans-4,5-substituted 5-bromocyclopentenone derivatives in good
      yields and with excellent enantioselectivities.

PMID- 21892500
TI  - Optically pure bulky (hetero)arylalkyl carbinols via kinetic resolution.
AB  - Planar chiral nucleophilic catalyst Fc-PIP was employed in the kinetic resolution
      of bulky (hetero)arylalkyl carbinols delivering unreacted alcohols with extremely
      high enantiomeric excess (>99.0% ees) in ideal conversions ranging from 50.4
      56.7%.

PMID- 21892502
TI  - Use of 6-methylpyridine-2-carbaldehydeoxime in nickel(II) carboxylate chemistry:
      synthetic, structural and magnetic properties of penta and hexanuclear complexes.
AB  - The use of 6-methylpyridine-2-carbaldehydeoxime ligand (6-mepaoH), in nickel(II)
      chemistry has been investigated and three new clusters isolated in mild
      conditions. Depending on the nature of the metal starting salts and the reaction
      conditions, the Ni(II)/6-mepaoH system has provided access to the complexes
      [Ni(6)(O(2)CPh)(6)(6-mepao)(6)] (1), [Ni(6)(O(2)CMe)(6)(6-mepao)(6)] (2) and
      [Ni(5)(3-Cl-BzO)(4)(6-mepao)(4)(6-mepaoH)(2)(N(3))(2)] (3), where 3-Cl-BzO(-) is
      the 3-chlorobenzoate anion. Compounds 1 and 2 are two new members of the
      [Ni(6)(O(2)C-R)(oximato)(6)] family of hexanuclear complexes whereas 3 exhibits
      an unusual irregular bowtie topology including end-on azido bridges. The
      structures of the three compounds have been determined by single-crystal X-ray
      crystallography. Variable-temperature dc magnetic susceptibility studies were
      carried out for 1-3. The data indicate antiferromagnetic exchange for complexes 1
      and 2 and ferrimagnetic interaction for complex 3.

PMID- 21892503
TI  - Distribution of procyanidins and their metabolites in rat plasma and tissues
      after an acute intake of hazelnut extract.
AB  - Procyanidins are present in a wide range of dietary foods and their metabolism is
      well known. Nevertheless, the biological target and their distribution are topics
      lacking information. The purpose of the present work was to study the metabolism
      and distribution of procyanidins and their metabolites in rat plasma and
      different tissues, such as liver, brain, lung, kidney, intestine, testicle,
      spleen, heart and thymus, after 2 h of an acute intake of hazelnut extract rich
      in procyanidins (5 g kg(-1) of rat body weight). The interest of an acute intake
      of procyanidins instead of repeated low doses from daily ingestion of is to
      achieve a concentration of metabolites in the tissues that allows their detection
      and quantification. The results showed that catechin and epicatechin-glucuronide,
      methyl catechin and epicatechin-glucuronide and methyl catechin and epicatechin
      sulphate were detected in plasma samples at the MUmol level. On the other hand,
      catechin-glucuronide, methyl catechin-glucuronide and methyl catechin-sulphate
      were identified in some tissues, such as thymus, intestine, lung, kidney, spleen
      and testicle at the nmol level. Procyanidins with a low grade of polymerization
      (dimers and trimers) were detected in plasma samples and the intestine.
      Additionally, a wide range of simple aromatic acids from fermentation by the
      colonic microflora was detected in all tissues studied.

PMID- 21892504
TI  - Asymmetric anatase TiO2 nanocrystals with exposed high-index facets and their
      excellent lithium storage properties.
AB  - In this work, we demonstrate a unique organic solvent system to synthesize
      asymmetric anatase TiO(2) nanocrystals with a bipyramidal structure, where the
      upper pyramid is bound by (201) facets, and the lower pyramid is bound by (401)
      surfaces. Due to the high surface energy of these (401) high-index facets, the
      nanocrystals tend to assemble on these facets to minimize the free energy,
      leading to the formation of a dandelion-like hierarchical structure.

PMID- 21892505
TI  - New synthesis of spirocycles by utilizing in situ forming hypervalent iodine
      species.
AB  - A very effective spirocyclization procedure for installing nucleophiles (Nu =
      N(3), NO(2), SCN, SO(2)Tol, and halogens) via iodonium(III) salts has been
      developed using the combination of iodoarene and mCPBA. The high-yielding
      syntheses of the cyclohexadienone-type spirocyclic compounds 2 having varied
      functionalities in the skeletons have been achieved from the aryl alkynes 1 with
      the optimized bis(iodoarene) 3h.

PMID- 21892506
TI  - Acyl hydrazides as peptoid sub-monomers.
AB  - The use of acyl hydrazides as peptoid sub-monomers is investigated. We
      demonstrate here that azapeptoids derived entirely from acyl hydrazides can be
      made conveniently and efficiently using standard peptoid sub-monomer chemistry.
      Structural studies reveal that the main chain amide bond in these molecules
      predominantly adopts a trans conformation. A high-quality one bead one compound
      library of tetramers was made by split and pool synthesis and we found that the
      identity of the molecule on a single bead could be determined by tandem MALDI
      mass spectrometry.

PMID- 21892507
TI  - Potassium tert-butoxide mediated Heck-type cyclization/isomerization-benzofurans
      from organocatalytic radical cross-coupling reactions.
AB  - A transition metal-free Heck-type cyclization/isomerization reaction has been
      developed. Mediated by potassium tert-butoxide and phenanthroline a variety of
      benzofuran derivatives have been synthesized.

PMID- 21892508
TI  - CoFe2O4 magnetic nanoparticles as a peroxidase mimic mediated chemiluminescence
      for hydrogen peroxide and glucose.
AB  - This communication presents a new peroxidase mimic of CoFe(2)O(4) nanoparticles
      evaluated by the luminol-based chemiluminescent (CL) reaction. This offers a new
      method for evaluation and screening of the nanoparticles-based enzyme mimetics.

PMID- 21892509
TI  - When Cu4I4 cubane meets Cu3(pyrazolate)3 triangle: dynamic interplay between two
      classical luminophores functioning in a reversibly thermochromic coordination
      polymer.
AB  - A supramolecular dual emissive system incorporating two classical copper(I)
      cluster-based luminophores, namely, Cu(4)I(4) and Cu(3)Pz(3) (Pz = pyrazolate),
      is reported. The targeted luminescent coordination polymer exhibits reversible
      thermochromism spanning from green to orange-red.

PMID- 21892510
TI  - Dissociation of energy selected Sn(CH3)4(+), Sn(CH3)3Cl+, and Sn(CH3)3Br+ ions:
      evidence for isolated excited state dynamics.
AB  - The dissociation dynamics of Sn(CH(3))(4)(+), Sn(CH(3))(3)Cl(+), and
      Sn(CH(3))(3)Br(+) were investigated by threshold photoelectron photoion
      spectrometry using an electron imaging apparatus (iPEPICO) at the Swiss Light
      Source. The tetramethyltin ion was found to dissociate via Sn(CH(3))(4)(+) ->
      Sn(CH(3))(3)(+) + CH(3) -> Sn(CH(3))(2)(+) + 2CH(3), while the trimethyltin
      halide ions dissociated via methyl loss at low energies, and a competitive
      halogen loss at somewhat higher energies. The 0 K methyl loss onset for the three
      ions was found to be 9.410 +/- 0.020 eV, 10.058 +/- 0.020 eV, and 9.961 +/- 0.020
      eV, respectively. Statistical theory could not reproduce the observed onsets for
      the halogen loss steps in the halotrimethyltin ions. The halide loss signal as a
      function energy mimicked the excited state threshold photoelectron spectrum, from
      which we conclude that the halide loss from these ions takes place on an isolated
      excited state potential energy surface, which we describe by time dependent
      density functional calculations. The sequential loss of a second methyl group in
      the Sn(CH(3))(4)(+) ion, observed at about 3 eV higher energies than the first
      one, is also partially non-statistical. The derived product energy distribution
      resulting from the loss of the first methyl group is two-component with about 50%
      being statistical and the remainder associated with high translational energy
      products that peak at 2 eV. Time dependent DFT calculations show that a
      dissociative B state lies in the vicinity of the experimental measurements. We
      thus propose that 50% of the Sn(CH(3))(4)(+) ions produced in this energy range
      internally convert to the X state, on which they dissociate statistically, while
      the remainder dissociate directly from the repulsive B state leading to high
      kinetic energy products.

PMID- 21892511
TI  - Hydrogen bond dynamics in heavy water studied with quantum dynamical simulations.
AB  - The structure and dynamics of the hydrogen-bond network in heavy water (D(2)O) is
      studied as a function of the temperature using quantum dynamical simulations. Our
      approach combines an ab initio-based representation of the water interactions
      with an explicit quantum treatment of the molecular motion. A direct connection
      between the calculated linear and nonlinear vibrational spectra and the
      underlying molecular dynamics is made, which provides new insights into the
      rearrangement of the hydrogen-bond network in heavy water. A comparison with
      previous calculations on liquid H(2)O suggests that tunneling does not
      effectively contribute to the dynamics of the water hydrogen-bond network above
      the melting point. However, the effects of nuclear quantization are not
      negligible at all temperatures and become increasingly important near the melting
      point, which is in agreement with recent experimental analysis of the structural
      properties of liquid water as well as of the proton momentum distribution in
      supercooled water.

PMID- 21892512
TI  - Mechanochemistry: opportunities for new and cleaner synthesis.
AB  - The aim of this critical review is to provide a broad but digestible overview of
      mechanochemical synthesis, i.e. reactions conducted by grinding solid reactants
      together with no or minimal solvent. Although mechanochemistry has historically
      been a sideline approach to synthesis it may soon move into the mainstream
      because it is increasingly apparent that it can be practical, and even
      advantageous, and because of the opportunities it provides for developing more
      sustainable methods. Concentrating on recent advances, this article covers
      industrial aspects, inorganic materials, organic synthesis, cocrystallisation,
      pharmaceutical aspects, metal complexes (including metal-organic frameworks),
      supramolecular aspects and characterization methods. The historical development,
      mechanistic aspects, limitations and opportunities are also discussed (314
      references).

PMID- 21892513
TI  - Sulfo-click reaction via in situ generated thioacids and its application in
      kinetic target-guided synthesis.
AB  - Herein, we describe a practical, one-pot variant of the sulfo-click reaction, in
      which 9-fluorenylmethyl-protected thioesters are rapidly deprotected and reacted
      further with sulfonylazides to give N-acyl sulfonamides.

PMID- 21892514
TI  - Rapid determination of enantiomeric excess: a focus on optical approaches.
AB  - High-throughput screening (HTS) methods are becoming increasingly essential in
      discovering chiral catalysts or auxiliaries for asymmetric transformations due to
      the advent of parallel synthesis and combinatorial chemistry. Both parallel
      synthesis and combinatorial chemistry can lead to the exploration of a range of
      structural candidates and reaction conditions as a means to obtain the highest
      enantiomeric excess (ee) of a desired transformation. One current bottleneck in
      these approaches to asymmetric reactions is the determination of ee, which has
      led researchers to explore a wide range of HTS techniques. To be truly high
      throughput, it has been proposed that a technique that can analyse a thousand or
      more samples per day is needed. Many of the current approaches to this goal are
      based on optical methods because they allow for a rapid determination of ee due
      to quick data collection and their parallel analysis capabilities. In this
      critical review these techniques are reviewed with a discussion of their
      respective advantages and drawbacks, and with a contrast to chromatographic
      methods (180 references).

PMID- 21892515
TI  - Uterine pseudotumors.
AB  - Pseudotumoral uterine lesions include benign reactive and artefactual changes,
      epithelial and mesenchymal, which occasionally are incorrectly interpreted as
      malignant or even premalignant lesions. Although some of these changes may have
      architectural or cytological abnormality, they are different from those observed
      in premalignant and malignant uterine lesions. The most common pseudotumoral
      lesions of the endometrium include various types of epithelial and stromal
      metaplasia, pseudolymphomas, inflammatory pseudotumor, adenomyosis, post-therapy
      surgical changes, artefactual changes, etc. Most of these changes may coexist
      with endometrial hyperplasia or endometrial carcinoma, and also with some benign
      conditions such as polyps or in combination with hormonal therapy or even in
      normal cyclic endometrium. These associated endometrial changes may raise
      important issues regarding the diagnosis and subsequent therapy.

PMID- 21892516
TI  - Clinical, histopathological and therapeutic considerations in non-neoplastic
      abnormal uterine bleeding in menopause transition.
AB  - With the decline of ovarian hormonal function, from the fifth decade of life,
      women enter the menopause transition, during which bleeding becomes irregular in
      duration and time of occurrence. Secondary to ovarian dysfunction, developmental
      and maturation endometrial anomalies occur, which are clinically translated by
      abnormal uterine bleeding, which in many cases at this age can be caused by
      organic lesions (fibroma, polyps, endometritis, endometrial hyperplasia,
      adenomyosis, etc.). The retrospective study included a total of 256 patients with
      abnormal uterine bleeding in menopause transition. Statistics showed that the
      incidence of these types of bleeding increases with age (64.5%) and parity
      (30.5%), with symptoms consisting mostly in different clinical forms of abnormal
      uterine bleeding (62.1%), and leiomyomas prevailing at histopathological
      examination (49.6%). Progesterone replacement therapy was the first therapeutic
      choice for correcting these types of bleeding. Progesterone therapy is useful not
      only for therapeutic purposes to amend the bleeding, but also as a precaution
      against the development of endometrial carcinoma. Progestogens cancel the
      proliferative and mitogenic effect of estrogens, even when administered in
      sequential regimen 10-12 days per month.

PMID- 21892517
TI  - Molecular pathways and pathomorphology of colorectal cancers.
AB  - Colorectal carcinomas (CRCs) evolve through multiple pathways. These pathways may
      be defined based on two molecular features: (1) chromosomal instability and (2)
      chromosomal stability. Tumors showing chromosomal stability evolve through the so
      called microsatellite instability pathway. These types of tumors show different
      clinico-pathological features and need different therapy so very important to
      separate them. As Hematoxylin-Eosin (HE) based histology is influenced by the
      different genetic alterations of a tumor, it is reasonable that different gene
      expression profiles result in different HE morphology. Our aim was to find
      specific histomorphological features specific for colorectal tumors showing
      different molecular features. We analyzed the clinicopathological parameters of
      324 colorectal carcinomas, 26 hereditary non-polyposis colorectal cancers, 32
      sporadic high-level microsatellite-instable (MSI-H) cancers and 266
      microsatellite-stable or low-level microsatellite-instable (MSI-L) cancers among
      them. Our results showed that we could recognize different genetic types of
      tumors on the base of clinicopathological features like patient's age, tumor
      localization and histological characteristics of CRCs. Main histological
      parameters help in differentiation are inflammatory background, nuclear features
      and pattern of infiltration. Clinical parameters like clinical stage and
      localization and careful histological analysis helps to select molecular method
      to define molecular features and to select the most appropriate therapy of a
      given tumor.

PMID- 21892518
TI  - Clinical relevance of vascular endothelial growth factor-A in colorectal cancer.
AB  - PURPOSE: To study the expression status and clinical relevance of vascular
      endothelial growth factor-A (VEGF-A) in colorectal cancer (CRC) tissues.
      EXPERIMENTAL DESIGN: VEGF-A expression was investigated by immunohistochemistry
      in 89 cases with CRC. Some demographic and histopathological variables were
      compared with VEGF-A expression to determine the prognostic significance in CRC.
      RESULTS: VEGF-A (-) was found in 24 cases; (+), (++) and (+++) stainings were
      detected in 24, 35 and six cases, respectively. VEGF-A (-) was found in 20 of 58
      cases with left colon cancer, while only four of 31 cases with right colon cancer
      were VEGF-A (-) (p=0.024). There was a trend for lower tumor grade and lesser
      serosal invasion in cases with VEGF-A (-) samples (p=0.07 and p=0.079,
      respectively). Although the correlation was not statistically significant, there
      was a trend for lower death rate in cases with VEGF-A (-) tumor (p=0.087). The
      longest survival was found in cases with VEGF-A (-) tumor and the shortest
      survival was found in cases with VEGF-A (+++) tumor. Median survival for patients
      with VEGF-A (-), (+), (++) and (+++) tumors was 59, 47, 35 and 11 months,
      respectively (p=0.02). The Cox proportional hazards model identified stage IV
      disease and VEGF-A (+++) tumor as having the most important influences upon
      overall survival (odds ratio: 5.1, 95% confidence interval: 2.0-13.0 and odds
      ratio: 3.6, 95% confidence interval: 1.0-12.7, respectively), followed by serosal
      invasion (odds ratio: 2.4, 95% confidence interval: 1.0-5.9). CONCLUSIONS: This
      study shows that VEGF-A is a poor prognostic factor in cases with CRC, but the
      relatively small size of the study group precluded the correlation with the
      entire known prognostic indicator.

PMID- 21892519
TI  - Mucinous adenocarcinoma of the colon - a histochemical study.
AB  - Colorectal carcinoma is a major cause of cancer associated with a high rate of
      morbidity and mortality in the western world. One of the pathologic features
      considered to be important for prognostic is mucin production. Many authors
      confirmed that colon carcinomas with high mucin content tend to re-occur locally
      and carry a poor prognosis. For histochemical evaluation of mucin content, we
      investigated 149 patients who underwent surgical resection of sporadic colon
      adenocarcinomas, all over a 5-year period. For histological classification we
      used the WHO recommendation (2000) and to be more accurate we sub-classified
      mucinous adenocarcinomas by morphometrical analysis in three categories: pure
      mucinous, with extracellular mucin more than 80% of the tumoral volume; mixed
      type, with 50-80% extracellular mucin; and mixed type with less than 50%
      extracellular mucin. For histochemical investigation, we used stains such as:
      mucicarmine, PAS / Alcian Blue and High Iron Diamine / Alcian Blue. Our study
      proved the predominance of mixed mucinous adenocarcinomas with less than 50%
      extracellular mucin, followed by the pure mucinous type. From the biochemical
      composition's point of view, the predominant cases were those with acidic mucins,
      especially in pure mucinous adenocarcinomas (>90%), while those with mixtures of
      acidic and neutral mucins were present in 62% of the cases. In addition, our
      study showed the prevalence of sialomucins over sulphomucins (68%), particularly
      in pure mucinous adenocarcinomas (77%). Clinical pure mucinous forms were
      detected mainly in advanced stages, but in terms of lymph node metastasis rate,
      they were secondary after mixed type with 50-80% extracellular mucin.

PMID- 21892520
TI  - The association of the rs1049353 polymorphism of the CNR1 gene with
      hypoadiponectinemia.
AB  - The endocannabinoid system (ECS) is an important physiological system that
      modulates appetite, food intake, energy homeostasis, substance addiction. It is
      comprised of the cannabinoid receptors (CB1 and CB2), the endogenous lipid
      ligands of these receptors and the enzymes that mediate the endogenous ligands'
      biosynthesis and degradation. CB1 receptor is expressed in the brain, adipose
      tissue, liver, skeletal muscle, gastrointestinal tract and pancreas. The CB1
      receptor is encoded by CNR1 gene located at 6q14-q15 level. The aim of our study
      was to investigate the possible correlation between rs1049353 polymorphism of the
      CNR1 gene with levels of adiponectin in a group of subjects from Romania. The
      study included 305 subjects divided in two groups according to their fasting
      adiponectin levels. Fasting adiponectin levels were determined using ELISA
      technique. The genotyping of the rs1049353 polymorphism of the CNR1 gene was made
      using the Real-Time PCR technique. The statistical analysis was performed using
      De Finetti's program. The differences between the allelic frequencies indicated
      that the presence of G-wild allele seems to confer risk for expressing low levels
      of adiponectin (OR=1.917; 95%C.I.=1.353-2.715; p=0.00023) and A-mutant allele
      seems to be protective (OR=0.522; 95%C.I.=0.368-0.739; p=0.00023). At the test of
      allelic positivity, the presence of the G-allele conferred risk of
      hypoadiponectinemia (OR=2.113; 95%C.I.=1.324-3.373). In conclusion, this study
      indicates that the rs1049353 polymorphism of the CNR1 gene is associated with
      decreased levels of adiponectin. Further research is needed in order to elucidate
      the link between the polymorphisms of the CNR1 gene and adiponectin levels.

PMID- 21892521
TI  - Hyperplastic polyps and serrated adenomas: precancerous lesions with mixed
      immunophenotype.
AB  - Our immunohistochemical study wants to be a contribution to clarifying the
      adenoma-carcinoma sequence and serrated pathway of colorectal carcinogenesis.
      Thus, we performed immunohistochemical analysis of hyperplastic polyps (HP),
      serrated adenomas (SA), and classical adenomas (tubular adenomas - TA and
      tubulovillous adenomas - TVA) and carcinomas developed from adenomas (CA) using
      expression of p53, Ki-67, c-myc, APC, MSH2 and Ets-1 proteins. Because of
      correlation of the expression of these proteins, we propose several
      immunophenotypes, which show modifications along the known carcinogenetic
      mechanisms. Along the adenoma-carcinoma sequence we noted an increase in the
      expression of p53, Ki-67, c-myc and Ets-1, and a decrease in APC expression. The
      majority of TAs and TVAs are characterized by p53+/Ki-67+, p53+/c-myc+,
      p53+/APC+, and Ets-/p53+, Ets-/Ki-67+ immunophenotypes. The majority of HPs and
      SAs are Ets-/p53-, Ets-/Ki-67+, Ets-/c-myc+, APC+/MSH2-. In approximately 1/3 of
      the hyperplastic polyps and serrated adenomas, we noted that the decrease in
      expression of MSH2 is associated with an increase in the expression of p53, c
      myc, Ki-67, and Ets-1. Thus, we can conclude that a group of hyperplastic polyps
      and serrated adenomas display similar immunohistochemical characteristics to
      tubular and tubulovillous adenomas, which delineates a group of precancerous
      lesions that can develop via mixed carcinogenic pathways.

PMID- 21892522
TI  - Isolation and characterization of chorionic mesenchyal stem cells from the
      placenta.
AB  - The aim of the study was the isolation and characterization of mesenchymal stem
      cells from the placental chorion from a genotypical and phenotypical point of
      view. The placentas included in the study were derived from term pregnancies with
      a normal evolution. Along with the placentas, umbilical cord blood, maternal and
      newborn peripheral blood samples were taken. The isolation and culture of
      chorionic and, incidentally, trophoblastic cells was followed by the
      determination of markers of the former cells. They expressed proteins and genes
      characteristic of stem cells. Immunofluorescence and evaluation of gene
      expression evidenced the pluripotential properties of these cells and also their
      higher position on the differentiation pathway. HLA expression provides
      information that might help explain the immunological mechanisms of tolerance
      between the maternal organism and fetal structures.

PMID- 21892523
TI  - Neuroimaging parameters in early open spina bifida detection. Further benefit in
      first trimester screening?
AB  - OBJECTIVE: Morphological investigation of the central nervous system (CNS) in
      fetuses with positive markers for open spina bifida (OSB) detection, visualized
      by ultrasound during the first trimester of pregnancy. MATERIALS AND METHODS:
      Data from fetuses that underwent routine first trimester ultrasound scan in our
      center during September 2007-March 2011 and presented abnormal aspects of the
      fourth ventricle, also referred as intracranial translucency (IT), provided the
      morphological support to evaluate CNS features. A neuro-histological study of
      posterior cerebral fossa illustrated anatomical features of the structures
      involved in the sonographic first trimester detection of neural tube defects.
      RESULTS: Abnormal IT aspects were found in OSB cases examined in the first
      trimester, but also in other severe cerebral abnormalities. Brain stem antero
      posterior diameter (BS) and brain stem to occipital bone (BSOB) ratio may be more
      specific for OSB detection. Correlations between histological aspects of
      posterior brain fossa and ultrasound standard assessment have been made;
      highlighting the anatomical features involved by the new techniques developed for
      OSB early detection. CONCLUSIONS: Preliminary results show that modern
      sonographic protocols are capable to detect abnormalities in the morphometry of
      the posterior brain. First trimester fourth ventricle abnormalities should be
      followed by careful CNS evaluation because are likely to appear in OSB affected
      fetuses, but also in other CNS severe anomalies; in such cases, normal BS and
      BSOB ratio may serve as indirect argument for spine integrity, if specificity is
      confirmed in large series of fetuses.

PMID- 21892524
TI  - The effect of distraction rate on bone histological and histomorphometrical
      properties in an ovine mandible model.
AB  - Lengthening the mandible by distraction osteogenesis (DO) is nowadays a well
      recognized technique in maxillofacial surgery. This study compared two different
      distraction rates and evaluated histological and histomorphometrical properties
      of the distracted bone in an experimental ovine mandible model with the goal of
      elaborating a universally accepted distraction protocol. STUDY DESIGN: Tissue
      blocks of regenerated bone were harvested from twelve young adult sheep. DO was
      performed on the mandibular midline after five days of latency period. The sheep
      were divided into two groups. The first group underwent activation of 0.8 mm/day
      during 12 days resulting in 9.6 mm of new bone while the second group followed a
      geometric rate pattern of 0.2 mm - three days, 0.4 mm - three days, 0.8 mm -
      three days and 1.6 mm - three days resulting in 9 mm of new bone. The regenerated
      bone was histologically and histomorphometrically analyzed after 30, 45 and 60
      days of consolidation. The relative osteoid volume (OV/TTV) was significantly
      increased in the geometric rate distraction group (p=0.015) comparing with linear
      distraction group while the relative bone volume (BV/TTV) was significantly
      increased in the linear distraction group (p=0.019) compared to the geometric
      distraction group.

PMID- 21892525
TI  - Cone beam computed tomography observations of the lingual foramina and their bony
      canals in the median region of the mandible.
AB  - PURPOSE: To investigate by means of CBCT the presence of lingual foramina and
      their bony canals in the midline of the mandible and to describe their anatomical
      characteristics. MATERIALS AND METHODS: CBCT examinations of 36 patients were
      carefully examined in the median region of the mandible in order to detect the
      lingual foramina and their corresponding vascular canals. Their presence, number,
      position, diameter and trajectory were established. RESULTS: Lingual foramina in
      the midline of the mandible were observed in all 36 subjects. The number of
      canals varied from one to four, with the following distribution: one canal in
      71.9% of the cases, two canals in 9.4%, three in 15.6%, and four canals in 3.1%
      of the cases. The average diameter of the canals was 0.84 mm. The average
      distance from the foramina to the base of the mandible was of 11.2 mm. 19.4% of
      the vascular canals penetrated only the lingual third of the width, 52.8% reached
      the middle third of the mandible and 27.8% of the canals spread to the buccal
      third. CONCLUSIONS: CBCT is a useful tool in planning an implant treatment. It
      can reveal multiple anatomic features of the mandible, including the presence and
      the morphology of the lingual foramina and their vascular canals in the median
      region of the mandible. Clinicians should acknowledge the presence of these
      anatomical structures and should be aware of their possible implications.

PMID- 21892526
TI  - Histopathological aspects of benign epithelial tumors located in areas of
      friction or chronic irritation of the tongue.
AB  - Besides lesions considered to be premalignant (such as erythroplasia, Bowen
      disease), a number of other potentially malignant lesions with higher or lower
      degree of epithelial dysplasia depending on the keratinization degree or
      determined by the action of carcinogens and irritants substances are described in
      the oral mucosa. Although they are practically considered the most harmless
      formations located on the oral mucosa, papillomas and condylomas are also the
      most frequent. In this study (conducted on a total of 38 cases with benign
      neoplasia) we planned a histopathological evaluation of surgical excision samples
      obtained from interventions on lingual neoplasias and harvested from the areas
      most exposed to chronic trauma or the areas in direct contact with mechanical
      irritants, in order to determine the histopathological pattern of the different
      types of histopathological lesions, the possible presence of keratosis-type
      changes or even possible dysplasias.

PMID- 21892527
TI  - Angiogenesis in the pathogenesis of pterygium.
AB  - Pterygium represents an epithelial hyperplasia associated with fibro-vascular
      growth. It is an active process, associate with cellular proliferation,
      remodeling of the connective tissue, angiogenesis and inflammation. The aim of
      this study consists of emphasizing angiogenesis involvement in the pterygium
      pathogeny. The material used for this study consisted of 21 pterygion fragments
      surgically removed in the Ophthalmology Clinic of the Emergency County Hospital,
      Craiova. Nine patients were men, 22 were women, and they were aged between 58 and
      81 years. Ten fragments of epibulbar conjunctiva from the vicinity of the sclero
      corneal limbus were used as control tissue. They were initially histological
      processed by paraffin inclusion. The immunohistochemical processing was made in
      the Histological, Histopathological and Immunohistochemical Techniques Laboratory
      of the University of Medicine and Pharmacy of Craiova. The working technique used
      was ABC/HRP (Avidin complexed with biotinylated peroxidase). Angiogenesis in the
      pterygion was investigated with CD31 marker that allows the identification of the
      vascular endothelium and the establishment of the vascular microdensity and with
      VEGF, which allowed the identification of the main source of proangiogenic
      factors in pterygium. Our study emphasized the existence of a much richer
      vascularization at the level of the pterygium, compared with the one of the
      normal conjunctiva. The respective blood vessels were best represented in the
      subepithelial conjunctive, due to the increased necessities of the proliferating
      pterygium epithelium. The morphology of the blood vessels is specific for the
      neoformation vessels, which have a small caliber, are branched and have a rarely
      visible lumen. The investigation of the vascular microdensity has shown the
      existence of an intense angiogenesis process at the level of the pterygium and
      the overexpression of the VEGF, mainly in the proliferating structures of the
      pterygium, plead for the pathogenic involvement of this growth factor in the
      development of the pterygium.

PMID- 21892528
TI  - Fractal analysis differentiation of nuclear and vascular patterns in
      hepatocellular carcinomas and hepatic metastasis.
AB  - Hepatocellular carcinoma (HCC) currently represents the fifth most common cancer
      worldwide, while being the third leading cause of cancer death. Fractal analysis
      is a novel tool used in quantitative and qualitative image assessment. Vascular
      patterns and cellular nuclei particularities in tumoral pathology make ideal
      candidates for this technique. Our aim was to apply fractal analysis in
      quantifying nuclear chromatin patterns and vascular axels in order to identify
      differences between images of primary HCC, liver metastasis (LM) and surrounding
      normal liver tissue. Formalin-fixed, paraffin-embedded tissue sections from 40
      cases of HCC and 40 LM of various origins were used. We performed Hematoxylin
      staining for nuclear chromatin as well as immunohistochemical staining for
      vascular patterns. High-resolution images were captured; nuclear and vascular
      morphologies were assessed on binarized skeleton masks using the fractal box
      counting method. Analysis was performed using the free, public domain Java-based
      image processing tool, ImageJ, which provided the fractal dimensions (FDs) for
      each studied element. Statistical analysis was performed using the ANOVA test
      with Bonferroni post-tests and t-tests for paired samples. Fractal analysis of
      vascular patterns clearly differentiated between tumoral tissue and normal
      surrounding tissue (p<0.01). Further analysis of nuclear FDs improved the
      specificity of these results, providing clear differentiation between
      pathological and normal tissue (p<0.01). When comparing primary HCC images with
      metastatic formations, we encountered statistically significant differences in
      nuclear chromatin assessment. However, blood vessels had a higher FD in primary
      tumors when compared with liver metastasis (p<0.05) and also allowed for a
      differentiation between primary liver tumors with and without
      neurodifferentiation. Fractal analysis represents a potent tool for
      discriminating between tumoral and non-tumoral tissue images. It provides
      accurate, quantifiable data, which can be easily correlated with the pathology at
      hand. Primary and metastatic liver tissue can be differentiated to some extent,
      however further studies, possibly including other variables (cellular matrix for
      instance) are needed in order to validate the method.

PMID- 21892529
TI  - Vascular anatomical variants in renal surgery: classic and robotic approach.
AB  - INTRODUCTION AND OBJECTIVES: Conservative renal surgery is based on the nephron
      sparing principle. Renal arterial vascularization is of terminal type and the
      occlusion of an artery generates the necrosis of the corresponding region. The
      aim of this research is to analyze the anatomic particularities of the renal
      vascular system as they are highlighted in the course of standard and robotic
      surgeries. PATIENTS AND METHODS: Between May 2006 and November 2010 we have
      performed 35 partial nephrectomies out of which 30 cases (85.7%) were performed
      by standard surgical approach and the other five (14%) were robot-assisted. In
      the same interval, we have done 103 pyeloplasties to obstruct the pyeloureteral
      junction: 65 (63%) were carried through by standard surgical approach, 32 (31%)
      by laparoscopic approach and six cases (6%) were robot-assisted. RESULTS AND
      DISCUSSION: In 20 (54.3%) of cases, nine (25.7%) had two renal arteries (both
      superior and inferior), five (14.2%) had early ramifications of the renal artery
      outside the renal sinus, four (11.4%) patients showed two renal veins, one
      patient lacked the prepyelic venous plane, and in one patient we have found
      duplicate abdominal vena cava. Out of all the pyeloplasty cases, 31 (30%) showed
      an obstruction of the renal collecting system by crossing with a segmental artery
      or with a vein. CONCLUSIONS: Efficient renal surgery implies good knowledge of
      anatomical particularities of the renal vascular. The minimally invasive approach
      by robotic laparoscopy remains an essential coordinate in renal surgery and
      allows an efficient preparing of the vascular capital.

PMID- 21892530
TI  - Morphological and topographical anatomy of nutrient foramina in human upper limb
      long bones and their surgical importance.
AB  - OBJECTIVES: To study the morphology and topography of nutrient foramina and to
      determine the foraminal index of the upper limb long bones. MATERIALS AND
      METHODS: The study comprised 243 upper limb long bones, which included humeri,
      radii, and ulnae. The nutrient foramina were identified macroscopically in all
      the bones and an elastic rubber band was applied around these foramina. The bones
      were photographed with the digital camera and foramen index was calculated. Each
      bone was divided into five equal parts and was analyzed topographically. RESULTS:
      From our observations, 93.8% of the humeri had single nutrient foramen. The
      double foramen was observed in 3.1% of the cases and the foramen was found absent
      in 3.1% of the humeri. In case of radius, 94.4% had single foramen, 1.4% had
      double foramen, and in 4.2% of the cases it was absent. With respect to ulna, all
      the 75 bones had single foramen. The mean foraminal index was 57.6 for the
      humerus, 34.4 for both the ulna and radius. The majority (70%) of the foramina in
      humerus were located at the 3/5th part, 83.6% of the ulnae foramina at the 2/5th
      part and 87.7% of the radii foramina at the 2/5th part. CONCLUSIONS: The study
      has provided additional information on the morphology and topography of nutrient
      foramina in upper limb long bones. The knowledge about these foramina is useful
      in certain surgical procedures to preserve the circulation. As microvascular bone
      transfer is becoming more popular, a convention for the anatomical description of
      these foramina is important.

PMID- 21892531
TI  - Correlation between albuminemia, natremia and survival rates in patients with
      hepatorenal syndrome.
AB  - A two years prospective study was developed, based on the monitoring of 84
      patients with cirrhosis and elevated serum creatinine; 33 patients met the
      diagnostic criteria for the hepatorenal syndrome. In these 33 patients, survival
      rate has been studied in correlation with hepatorenal syndrome types, serum
      albumin and natremia.

PMID- 21892532
TI  - Histological evaluation of pure NOTES - related complications in a survival
      animal study.
AB  - Considered as an extension of both laparoscopic surgery and interventional
      endoscopy, natural orifice transluminal endoscopic surgery (NOTES) is emerging as
      a new alternative of minimal invasive surgery. Literature on the gastrointestinal
      complications of this novel technique is sparse. The goal of this study was the
      histopathologic evaluation of postoperative complications in a NOTES experimental
      animal group. Ten female pigs (Sus scrofus domesticus) underwent transgastric
      endoscopic oophorectomy and tubectomy followed by gastric closure using OTSC
      clips. Fourteen days after surgery, the animals were sacrificed. Based on the
      gross examination during necropsy focused excisional biopsies were performed.
      Gross and microscopic evidence of gastric ulcer distal to the puncture site and
      perigastric lymph node abscess were found on one animal. Histological evaluation
      plays a determinant role in the correct evaluation of postoperative complications
      of pure NOTES procedures.

PMID- 21892534
TI  - Enhanced dendritic arborization of hippocampal CA3 neurons by Bacopa monniera
      extract treatment in adult rats.
AB  - OBJECTIVE: Bacopa monniera (BM), a traditional Ayurvedic medicine has been used
      in treatment for a number of disorders, particularly those involving anxiety,
      intellect and poor memory. The current study examined the effects of standardized
      extract of Bacopa monniera on the dendritic morphology in adult rats of
      hippocampal CA3 neurons, one of the regions concerned with learning and memory.
      MATERIALS AND METHODS: Adult Wistar (2.5-month-old) rats were designated into 2-,
      4- and 6-week treatment groups. Rats in each of these groups were divided into 20
      mg/kg, 40 mg/kg and 80 mg/kg dose groups (n=8 for each dose). These rats along
      with age-matched control rats were then subjected to spatial learning (T-maze)
      and passive avoidance tests. Subsequent to the T-maze and passive avoidance
      tests, these rats were killed by decapitation, brains were removed and
      hippocampal neurons were impregnated with silver nitrate (Golgi staining).
      Hippocampal CA3 neurons were traced using camera lucida. Dendritic branching
      points (a measure of dendritic arborization) and dendritic intersections (a
      measure of dendritic length) were quantified. These data were compared with
      control rats. RESULTS AND CONCLUSIONS: The results showed improvement in spatial
      learning performance and enhanced memory retention in rats treated with BM
      extract. There was a significant increase in the dendritic intersections and
      dendritic branching points along the length of both apical and basal dendrites in
      rats treated with BM extract for four and six weeks. However, the rats treated
      with BM extract for two weeks did not show any significant change in hippocampal
      CA3 neuronal dendritic arborization. We conclude that constituents present in BM
      extract have neuronal dendritic growth stimulating properties.

PMID- 21892533
TI  - Morphometry and CT measurements of useful bony landmarks of skull base.
AB  - OBJECTIVE: Aim of this study was to determine the distance between Henle's spine
      (HS) on the temporal bone to the clinically important bony landmarks on the dry
      skulls that will act as a guide in various surgical procedures on skull base.
      Distances from the head of malleus (HOM) to surgically relevant landmarks were
      also studied on CT images. MATERIALS AND METHODS: Thirty-nine adult preserved dry
      skulls were studied bilaterally. The parapetrosal triangle bounded by
      spinopterygoidal, bispinal and the midsagittal lines was identified. The location
      of the HS and its distance from the various important anatomical structures were
      measured. In addition, five CT images, where distances from the HOM to various
      anatomical landmarks were measured. RESULTS: The mean and range of distances from
      the HS to various important anatomical landmarks on the spinopterygoidal line,
      bispinal line and in the parapetrosal triangle were tabulated. The mean and range
      of CT-based measurements of distances from HOM to other anatomical landmarks were
      also noted. CONCLUSIONS: The knowledge of unvarying relationship of the HS and
      the HOM to the various structures of the skull would assume significance while
      planning surgeries around the temporal bone by guiding the direction and degree
      of bone removal. Statistical differences between the two genders showed
      significant difference only in the distance between the HS to the medial margin
      of the external orifice of carotid canal. Therefore, these landmarks can also be
      applied as references for various surgeries of middle cranial fossa, as well as
      transpetrosal and transmastoid approaches.

PMID- 21892535
TI  - Angiogenesis assessment in experimental third degree skin burns: a histological
      and immunohistochemical study.
AB  - In the past 30 years, after the discovery of vascular proliferation factors,
      angiogenesis is one of the most intensively studied fields. Restoring the
      vascular network after burn injury is essential for healing, as it brings oxygen
      and nutrients to injured tissues, improves the contribution of inflammatory cells
      and prepares the damaged area for repair and tissue regeneration. To study the
      process of angiogenesis we used seven groups of five animals, each of adult
      Wistar rats, which were inflicted with third degree skin burns. From each group
      of animals, we sampled at successive intervals of three days the entire burnt
      wound with a ring of surrounding normal skin. Sampled skin fragments were
      processed for paraffin inclusion, sectioned with a microtome and stained with
      Hematoxylin-Eosin or Masson trichrome. The samples were also analyzed using
      single chromogenic immunohistochemistry or double immunofluorescence for the
      presence of CD34 and alpha smooth muscle actin (alpha-SMA). Angiogenesis process
      started at about three days after the burn infliction, with the appearance of
      tubular structures lined by CD34-positive cells. Subsequently, these cells showed
      intense proliferative activity that generated a network that included progressive
      neovascularization around the wound surface. Maximum vascular proliferation
      occurred at 9-15 days after injury, when the number of capillaries reached
      229/mm2, and the total area of capillary angiogenesis at 100.27 MUm2 (about 10%
      of the section area). Subsequently, the process of angiogenesis was gradually
      reduced, but remained at moderate levels after wound healing. During the process
      of angiogenesis, there was a very close relationship between CD34-positive cells
      and pericytes (as alpha-SMA-positive).

PMID- 21892536
TI  - Vertebral bone metastasis in breast cancer: a case report.
AB  - BACKGROUND: We report here a case of a 66-year-old woman with a very aggressive
      form of breast carcinoma, having both liver and bone dissemination points. CASE
      DESCRIPTION: The patient was admitted for a rapid onset disk-herniation-like
      syndrome, but which on further investigation proved to be in fact a metastatic
      case of breast cancer. We found evidence of disseminations at least in the lumbar
      vertebral bodies and the liver. Pathological analysis of the available vertebral
      metastasis revealed a HER2+ molecular pattern, accordingly to the newly evolving
      molecular typing of breast cancers. Despite a rapid treatment instauration, the
      patient reacted poorly to taxanes and octeoclast inhibitors, and died after less
      than 11 months from admitting to the hospital. CONCLUSIONS: This is a rare case
      of an aggressive breast carcinoma identified initially after the vertebral
      metastases themselves that induced a non-specific symptomatology.

PMID- 21892537
TI  - Follow-up of childhood chronic myelogenous leukemia with monitoring the BCR-ABL
      fusion gene expression in peripheral blood.
AB  - Chronic myelogenous leukemia (CML) accounts for 15-20% of adult leukemias but is
      very rare in children (2%). Fewer than 10% of CML patients are younger than 20
      years. CML is a myeloproliferative disorder characterized by the presence of the
      Philadelphia chromosome or the BCR-ABL fusion oncogene. The objective of this
      paper is to present the monitoring of imatinib therapy in two children with CML
      by the BCR-ABL fusion gene expression assessment from peripheral blood with
      quantitative real-time polymerase chain reaction (PCR) method. PATIENTS AND
      METHODS: The 18 and six months follow-up of the patients included clinical
      examination, routine laboratory tests, bone marrow aspirate investigation
      including cytogenetic tests and the major BCR-ABL fusion gene expression
      measurement with qRT-PCR method from the peripheral blood. RESULTS: Patient No. 1
      diagnosed with chronic phase CML showed excellent adherence to daily 400 mg
      imatinib treatment and achieved complete hematologic (CHR) and cytogenetic
      response (CCR) by three months and major molecular response (MMR) by 12 months,
      with lack of side effects due to imatinib. Patient No. 2 experienced severe
      hematologic toxicity, which necessitated temporary withdrawal of the drug.
      Transient non-compliance together with imatinib dose reduction has driven to
      treatment failure. In this case, mutational analysis is warranted. CONCLUSIONS:
      BCR-ABL fusion gene expression level measurement from peripheral blood with qRT
      PCR method is an excellent tool in the follow-up of CML patients.

PMID- 21892538
TI  - Sinusoidal hemangioma of the arm: case report and review of literature.
AB  - Sinusoidal hemangioma is a rare variant of cavernous hemangioma that develops
      more frequently subcutaneous, often in the extremities. We report the case of a
      19-year-old patient three times operated for a recurrent soft tissue tumor,
      located in the distal third of the antero-medial face of the right arm. Treatment
      was surgical and consisted of microsurgical excision of a tumor with dermal and
      intramuscular location. Histopathological analysis showed a nodular proliferation
      of interconnected thin-walled blood vessels, sinusoidal growth pattern and the
      presence of pseudopapillary structures. Immunohistochemical investigations were
      positive for CD31, CD34 and Ki67 index decreased, confirming the benign nature of
      vascular proliferation.

PMID- 21892539
TI  - Dystrophic epidermolysis bullosa: two case reports.
AB  - We identified the mutations in two patients with different phenotypes of
      dystrophic epidermolysis bullosa (DEB). We performed molecular diagnosis to a
      patient aged 45 years who showed the typical severe generalized autosomal
      recessive DEB signs when admitted to the hospital. The other patient is a 4-month
      old boy who showed a moderate clinical aspect of DEB, dominated by nail
      dystrophy. The molecular diagnosis disclosed in the first patient the presence of
      a heterozygous mutation consisting of a nucleotide substitution that lead to a
      splice site mutation, namely 425-2 A>G, associated to a premature termination
      codon, in exon 5, namely c.553 C>T, p.R185X and in the second patient a
      heterozygous substitution at nucleotide position 6100 that converts a glycine
      amino acid to arginine (6100G>A). The mutation is designated G2034R. We conclude
      that molecular diagnosis is the conclusive EBD investigation, maps the phenotype
      of a patient with his genotype and thus allows a better understanding of the
      disease mechanism and the development of gene therapy. Molecular diagnosis also
      enables genetic counseling and prenatal diagnosis.

PMID- 21892540
TI  - Endodontic treatment of a mandibular canine with two roots.
AB  - Lower canine is a tooth with a robust, long root and very good implantation,
      making it a valuable abutment tooth for any type of prosthetic treatment. In
      order to treat it conservatively and to prevent its loss from the dental arch it
      is necessary to accomplish a correct and complete endodontic treatment, which
      involves knowledge of all its morphological variation. The mandibular canine
      usually presents one root with a single large canal centrally located. The
      possible anatomical variations are the existence of a single root with two canals
      and of two different roots, each having a canal. The incidence of lower canines
      with two roots is usually low, as described in various studies, but their
      presence in everyday practice shows that the clinician must consider them if he
      wants to prevent dental endodontic treatment failure. This article presents a
      relatively rare case of a patient whose right mandibular canine has two roots and
      two canals. Although the frequency of mandibular canines with two roots is very
      low, we must not forget that we can deal with such cases, which can obviously
      occur even in patients in our country, as the ones described in foreign specialty
      literature.

PMID- 21892541
TI  - Idiopathic orbital inflammatory pseudotumor: case report and review of the
      literature.
AB  - Idiopathic orbital inflammatory pseudotumor is a chronic neoplasm-like
      inflammatory reaction, usually affecting the orbital tissues of both eyes and
      orbit. Isolated optic nerve involvement by the idiopathic inflammatory process is
      a rare finding and very few reports are available. Here a case of an isolated
      orbital nerve inflammatory pseudotumor presenting with gradually progressive
      unilateral loss of vision is described. It showed dramatic response to surgery
      and steroid treatment and its differential diagnoses are discussed.

PMID- 21892542
TI  - More actors, different play: sphenoethmoid cell intimately related to the
      maxillary nerve canal and cavernous sinus apex.
AB  - The sphenoid sinus is one of the most morphologically variable and surgically
      important structures of the skull base. Located below the sella turcica,
      neighbored by parasellar regions, such as the orbital apex, pterygopalatine fossa
      and lateral sellar region (cavernous sinus), it is clinically related to these
      and surgically relevant as corridor for various approaches. Moreover, at the
      sphenoethmoidal junction, important variations occur, most of these related to
      the presence of the Onodi cells and the intrasinusal protrusions of the optic
      nerve. That is why any identified and previously undescribed morphological
      variation at that level must be added to the well-established protocols, clinical
      and surgical. During a retrospective CT study of the sphenoid sinus anatomical
      features a previously unreported morphology was encountered and is reported here.
      It refers to a unilateral sphenoethmoid cell (SEC), Onodi-positive, not only
      overriding the superior aspect of the sphenoid but also its lateral side to get
      intimately related to the maxillary nerve. As that SEC expanded medially to the
      cavernous sinus apex, it altered the usual endosinusal morphological correlations
      and also added itself within the limits of the Mullan's triangle. It appears so
      that such postero-infero-lateral extended pneumatization of an Onodi cell alters
      the surgical landmarks and also can blur clinical pictures, by adding maxillary
      and pterygopalatine signs and symptoms.

PMID- 21892543
TI  - Undesirable dental hard tissue effects hypothetically linked to orthodontics - a
      microscopic study.
AB  - Like any other medical intervention, the orthodontic treatment may have, besides
      the positive effects, also unwanted secondary consequences. The aim of this study
      was to evaluate the changes present in dental hard tissue associated with
      orthodontic treatment. The stereo-microscopic ex vivo analysis was performed on
      two sets of maxillary first premolars undergoing orthodontic treatment for a long
      period of time (12 and 23 months); five teeth with other clinical situations were
      used as controls. By analyzing the teeth undergoing orthodontics, enamel color
      alterations were mainly found adjacent to the bracket, more pronounced in the
      gingival area, suggesting the need for a correct oral hygiene around it.
      Roughness was higher on the enamel surface corresponding to the bracket's base,
      aspect linked to the resign impregnation during bonding procedures. At the apical
      part, changes regarding contour, appearance and surface roughness were noticed.
      These modifications were suggestive for the presence of apical root resorption.
      The severity of root resorption was not correlated with the duration of
      treatment. In conclusion, through microscopic analysis changes that may be
      associated with orthodontic treatment have been observed in both crown and apical
      level.

PMID- 21892544
TI  - Secondary involvement of lymph nodes in Kaposi sarcoma.
AB  - Kaposi sarcoma is a low-grade neoplasm first described by Moricz Kaposi in 1872.
      Although many attempts have been made to explain its pathogenesis, its etiology
      still remains obscure. In this regard, many aspects of the disease's genetic,
      epidemiological and histopathological backgrounds are even today unclear. We
      present the case of a 57-year-old male patient, constant HIV negative, with a
      history of plaque-like lesions on his right foot approximately two years ago.
      Following surgical removal, a diagnosis of Kaposi sarcoma, plaque stage was
      settled. One year after, the patient was admitted to the hospital for pain in the
      right ankle and foot, associated to paresthesis and trophic lesions at this
      level. Similar lesions developed in the popliteal fossa. Biopsy and subsequent
      histological and immunohistochemical examination revealed a KS at that level. The
      most recent hospital admission revealed the appearance of an indolent
      lymphadenopathy in the groin. Our case represents a rare occurrence of Kaposi
      sarcoma at a HIV-negative patient, which, after several local recurrences and
      progressive behavior, produced a lymph node involvement at the groin level. The
      immunohistochemical assessments have confirmed the diagnosis.

PMID- 21892545
TI  - The lateral incisive canals of the adult hard palate - aberrant anatomy of a
      minor form of clefting?
AB  - Except the oral clefts and their associated dental development disturbances, no
      other discrete morphologies are reported in the literature as related to altered
      fusions of the fetal maxilla and premaxilla. We report here two cases related by
      the persistence in adult of an aberrant canal at the fusion site of the fetal
      premaxilla and maxilla. The first case presents an anastomosis of the superior
      anterior alveolar and greater palatine nerves, encountered during the dissection
      of a human adult male cadaver; that anastomosis, bilaterally present, projected
      on the aforementioned fusion site and traversed the hard palate to continue
      within the maxillary sinus wall. The second case evidenced on CT the unilateral
      presence of aberrant lateral incisive canals (LIC) at the level of the fetal
      premaxilla and maxilla fusion site; those canals, external (1.5 mm diameter) and
      internal (1.07 mm diameter), were corresponding as location to that one traversed
      by the aberrant anastomosis in the first case. Both LIC opened inferiorly but not
      superiorly, rather seeming to communicate with the bony canals within the nasal
      fossa floor at that level. We consider that such aberrant canals and nerves may
      represent very rare forms of clefting, previously undescribed; the possible
      anastomoses of the superior anterior alveolar and greater palatine nerves can be
      altered during a Le Fort I fracture and may be the morphology that can explain
      aberrant clinical nervous distributions at the level of the upper dentoalveolar
      arch and hard palate.

PMID- 21892546
TI  - Letter to the editor. Variant hepatic portal vein and incomplete celiac trunk:
      the anatomical context.

PMID- 21892547
TI  - [Evolution of the prison population mortality after introduction antiretroviral
      therapy (ART)].

PMID- 21892548
TI  - [Intervention of the case management nurse in hospital admissions of patients
      with HIV infection].
AB  - In countries with access to antiretroviral treatment such as ours, HIV is a
      chronic disease both characterized for being treated only in hospitals and for
      the aging of the affected population, the persistence of opportunist infections,
      the complexity of the antiretroviral treatment, the frequency of adverse effects
      due to therapies, drug interactions and the high costs of this disease for the
      Healthcare System. This could justify the need for the creation of the position
      of nurse case manager to monitor patients with HIV infection, admitted to
      conventional hospital wards, as a unifying element of the individual's needs and
      coordinate resources through proper planning and care management.

PMID- 21892549
TI  - [Causes and trends of mortality in a Spanish prison (1994-2009)].
AB  - BACKGROUND: There are a few mortality researches in prisons. To know this measure
      can to be important for take decisions of Public Health. The aim of the paper is
      to describe mortality and its trend in our prison. METHODS: This is a descriptive
      and retrospective study of the deaths between 01/01/1994 and 31/12/2009. Two
      periods of 8 years have been compared through exact test of Fisher in order to
      detect changes in causes of mortality. First of all, we made an indirect
      standardization of rates and compare mortality in our institution with other
      Spanish prisons. Through linear regression model we have settled in trends of
      mortality rates. RESULTS: Had 59 deaths, 58 in men with a median age 34.9 years
      old (28.7- 40.4). 64,4% were HIV+ . From 1994 to 2001 the main cause of mortality
      was VIH infection (48.6%) the second one was cardiovascular event (10.8%), while
      that between 2002 and 2009 this trend have change, cardiovascular event caused
      (31.8%) and VIH infection (22.07%) (p=0.026).The annual crude mortality rate
      decreased -0.485 deaths 0/00 inmates/year (IC 95%: -0.864 to -0.107).
      Standardizing rates, we get 42 deaths expected for the wholly period, with
      Standarized Mortality Ratio of 1.407 (I.C. 95%: 1.071 to 1.816). CONCLUSIONS: The
      main cause of mortality has been no-HIV diseases, among these mainly
      cardiovascular events. The trend of mortality rate has been decreasing although
      we observe 40.7% plus of deaths than we would expect.

PMID- 21892550
TI  - [Relationship between the number of hours of informal care and the mental health
      status of caregivers].
AB  - BACKGROUND: Mental health of caregivers is damaged by caregiving tasks. Studies
      are needed to determine the influence of several variables on the association
      between informal care and mental health. The aim of this paper is to analyse the
      effects of the time devoted to informal caregiving on the mental health of women
      and men in relation to the type of dependents. METHODS: National Health Survey
      2006, sample 29,478. VARIABLES: mental health state (GHQ-12), number of hours
      devoted to caregiving, age, social class, and functional support (Duke-UNC). A
      logistic regression analysis was performed to determine the probability of having
      poorer mental health according to the number of hours of caregiving, adjusted for
      age, social class and functional support. RESULTS: Women show poorer mental
      health when they spend more than 97 hours per week taking care of children
      [OR=1,372], more than 25 hours caring for persons over 74 years of age [OR=1,602
      between 25 and 48 hours; OR=1,467 49-96h.; OR=1,874 97-168h.], and when they
      devote some hours to provide care to adults with disabilities [OR=1,996 0-24h.;
      OR=2,507 25-48h.; OR=3,016 49-96h.; OR=1,651 97-168h.]. Men show deterioration in
      mental health when they devote a high number of hours to caring for persons over
      74 years [OR=2,810 97-168h.] and adults with disabilities [OR=3,411 97-168h.],
      and when they devote some hours to childcare [OR=1,595 0-24h.]. CONCLUSIONS: The
      effect of the number of hours devoted to caregiving on the mental health of
      caregivers is influenced by the type of dependents and the gender of the
      caregiver.

PMID- 21892551
TI  - [Variability in the control of oral anticoagulant therapy between primary care
      and hospital in Albacete (2009)].
AB  - BACKGROUND: After taking control of oral anticoagulant therapy in our health
      center it became necessary to detect possible differences with regard to hospital
      monitoring. The aim of our study was to determine the variability in the
      International Normalized Ratio (INR) values of patients on oral anticoagulant
      therapy (OAT), and the possible relation to control in primary care or hospital.
      METHODS: We analyzed the last 6 controls of 291 patients in an urban health
      centre in routine control by OAT. In order to analyze the variability, we
      calculated the standard deviation (SD) of natural logarithm (ln) of INR values,
      comparing by Student t test their mean between patients whose treatment had been
      scheduled in primary care and those on some occasions ruled by them and others in
      hospital. We compared also the proportion of controls within range in each group
      (chi2). RESULTS: 153 (52.6%) patients were women, and the mean age was 73.8 years
      (SD: 11.3). We analyzed a total of 1710 INR controls, of which 1412 have been
      validated by family physicians and 298 by haematologists; there were no
      significant differences in INR values. Patients whose treatment had been
      scheduled by professionals of the health centre had mean values of the SD of the
      ln of the INR of 6 controls analyzed significantly lower (p <0.0001) than in
      those who had taken a mixed control. Also, a higher proportion of controls within
      range (68.0% vs 38.6%, p <0.0001). CONCLUSIONS: Patients who are followed only by
      professionals in the health centre have less variability and more appropriate INR
      control than those with a mixed control health centre / hospital.

PMID- 21892552
TI  - [Trends in prevalence of risk factors and global cardiovascular risk in general
      population of albacete, Spain (1992-94 a 2004-06)].
AB  - BACKGROUND: To establish strategies for prevention of cardiovascular disease
      implies to know its epidemiology and evolution in time. The objective of this
      study is to know the prevalence of risk factors and cardiovascular risk in two
      moments during the following of a grownup general population. METHODS: Study of
      cohorts, followed at random selected general population during 12 years (1992-94
      to 2204-06). Two transversal studies were made, one at the beginning and the
      other one at the end of this follow-up. The population in this study was 18 years
      and older registered in the province of Albacete. Random sampling, stratified and
      two-stage. The sample size for the first cut was 2121 subjects and for second one
      1577. One specific anamnesis was made, physical examination, measurement of blood
      pressure, electrocardiogram and extraction of venous blood. The studied variables
      were: age, sex, personal and familiar antecedents, risk factors and global
      cardiovascular risk. RESULTS: 1322 subjects went to the appointment for the first
      examination (mean age 48.2 years. 53.6% women) and 997 for the second (mean age
      52.8 years. 56.7% women). Has Increased the prevalence of hypertension (32.7% to
      41,2%), diabetes (9,8 to 11,4%), obesity (27,8 to 34,3%) and hypercolesterolemia
      (47,5 to 53,5%), whereas smokers have decreased (32,6 to 23,7%) and have
      handicapped the average values of arterial pressure (132/81 to 129/73 mmHg),
      glycaemia (100,8 to 92,8 mg/dl) and LDL-cholesterol (128,7 to 116,7 mg/dl) and
      also a lowering of cardiovascular risk with Framingham (10,8% to 8,2%) and Score
      (2,3% to 1,6%). CONCLUSIONS: In the last years an increasing prevalence of risk
      factors has been seen (hypertension, diabetes and hypercolesterolemia), a better
      control of them, and lower prevalence of smoking and cardiovascular risk in the
      population has also be seen.

PMID- 21892553
TI  - [Public health service prescriptions of vaccines not included in systematic
      vaccination programs in Valencian community, Spain, during the period 2004-2009].
AB  - BACKGROUND: In the context of the policies of rational use of medicine, and in
      order to achieve an efficient management of the vaccinations programs, we expect
      to know the number of packings and cost of prescribed vaccines not included in
      the vaccination programs of Valencian Community and its departments during 2009
      and to analyze its evolution since 2004, focusing on an analysis of Heptavalent
      pneumococcal conjugate vaccine in children under two years old. METHODS:
      Retrospective descriptive study to analyze the prescriptions of vaccines in
      Valencian Community during 2009 and its evolution since 2004. VARIABLES: vaccine
      availability, number of packings, group of beneficiary (actives/pensioners),
      department, and cost of prescriptions. DATA SOURCES: Gestor de Prestacion
      Farmaceutica (GAIA) and Sistema Informacion Poblacional (SIP). RESULTS: In 2009
      prescribed vaccines on official national health system prescription forms that
      are not included in vaccination programs, supposed a cost of 683.445,71 ?
      corresponding to 17.353 packings (87% of the total prescribed vaccines).
      Heptavalent pneumococcal conjugate vaccine generated 72% of the total cost of
      vaccines not included in the vaccination programs. The trend from 2004 to 2009
      shows an increase in expenditure of 735.334 ? (24,66%) in 2005 from which there
      takes place a marked and gradual decrease that reaches 1.562.650,67 ? (-228.64%).
      The cost by departments of prescriptions per 1000 children under two years old of
      pneumococcal conjugate vaccine ranges between 17.377 and 324 ?. CONCLUSIONS: The
      declining trend of prescriptions, mainly of pneumococcal conjugate vaccines,
      continues during 2009. A great interdepartmental variability is observed,
      nevertheless, in rates of prescription that should be corrected.

PMID- 21892554
TI  - [Impact of a PET/CT facility in its community environment].
AB  - BACKGROUND: The PET/CT (Positron Emission Tomography/Computed Tomography)
      technique is currently expanding, with new facilities and indications appearing
      every year. Being mostly an outpatient technique, patients leave the facility
      when the study has been performed, although they still retain a certain amount of
      radiopharmaceutical. Therefore, setting up a PET/CT facility might involve a risk
      increase for the population. This study aims at estimating this risk. METHODS:
      Comprehensive measurements to estimate dose levels have been carried out in the
      PET/CT facility at Hospital General Universitario Gregorio Maranon. The
      population has been distributed into five categories according to their
      involvement in the studies and their radiation exposure. A quantitative dose
      estimation has been carried out. RESULTS: The risk associated with a PET/CT
      facility has been assessed and no risk increase has been detected. Staff dose is
      shown to be less than 2 MUSv per patient, ~20 MUSv for an accompanying person and
      ~40 MUSv for a relative. Citizens walking along with patients or sharing public
      transportation with them receive a dose that is below Madrid's background
      radiation. CONCLUSIONS: Values obtained are well below annual dose limits.
      Moreover, these results support the outpatient care of this kind of studies,
      because accompanying persons' and relatives' risk is negligible. The impact of a
      PET/CT facility does not involve an increase in risk for the general population.

PMID- 21892555
TI  - [Comorbidity and cardiovascular risk in subjects with initial diagnosis of
      hypercholesterolemia].
AB  - BACKGROUND: For a proper approach to the subjects, in which the presence of
      hypercholesterolemia is identified for the first time, is important to consider
      simultaneously both cardiovascular risk factors and the presence of other
      diseases. The purpose of our study was to describe the lipid profile of patients
      in which the presence of hypercholesterolemia is detected for the frist time and
      to determine their cardiovascular risk and comorbidity. METHODS: Observational
      cross-sectional study in a Primary Care setting. In 274 subjects with a plasma
      cholesterol level higher or equal to 200 mg / dL ("limit" hypercholesterolemia),
      selected by consecutive sampling, we assessed: lipid profile, cardiovascular risk
      factors and cardiovascular risk (SCORE and Castelli's atherogenic index),
      comorbidity (Charlson's Index) and sociodemographic characteristics. RESULTS: The
      mean cholesterol level was 232.9 mg/dl. Hypercholesterolaemia was reported
      "definite" (>= 250 mg / dl) in 21.1% (95% CI: 16.2 to 26.1). A 9.5% showed a
      cardiovascular risk >= 5%. Lipoprotein ratio of total cholesterol/HDL cholesterol
      was higher in men than in women (4.4 vs. 3.8, p <0.001) in subjects with
      Charlson's Comorbidity Index > = 1 (4.1 vs. 3.9, p = 0.04), in smokers (4.3 vs.
      3.9, p = 0.04) and in hypertensive subjects (4.2 vs. 3.9, p = 0.03), obese (4.2
      vs 3 , 7, p <0.05) or with the metabolic syndrome (4.4 vs 3.9, p = 0.02). We
      observed a higher proportion of subjects with moderate cardiovascular risk / high
      or cardiovascular disease in those with comorbidity (87.3% vs 42.3%, p <0.01).
      CONCLUSIONS: More than a third of the subjects in which "limit" cholesterol was
      identifiyed for the first time presents comorbidity, being "defined"
      hypercholesterolemia in 21.1% of the cases. Takeing in consideration the Score
      function assessment, one outif 10 subjects presents high cardiovascular mortality
      risk after 10 years. Both lipoprotein ratio and cardiovascular risk are markedly
      higher in subjects with comorbidity.

PMID- 21892556
TI  - [Patients' satisfaction with communication with their family doctors: comparison
      of three methods for assessing unmet needs].
AB  - BACKGROUND: Different aspects of the doctor-patient relationship were associated
      with satisfaction and other outcomes of the consultation. However, measurements
      of the perception of communication quality are often limited by the "ceiling
      effect". To evaluate the relationship and differences between three ways to
      obtain information regarding patient satisfaction and perception of unmet needs
      in communication aspects with your doctor. METHODS: An observational descriptive
      study was design. Patient perception regarding four communicational domains when
      attending family doctors measured by means of three different type of questions.
      RESULTS:  PARTICIPATION: 658 (91%) patients attending the consultation of 97
      physicians in 58 Health Centres. 401 (62%) of them were females. Average age 52
      years (TD:17,4; CI95%: 50,6-53,3 years), 401 females (62%: CI95%: 58,7-66,4%). In
      close ended questions, patients declared high rates of satisfaction for all the
      communicative domains studied: relationship 99,7% (CI95%: 98,8-99,9%), explaining
      reasons for consultation (CI95%: 94,4-97,7%), information regarding causes 96,2%
      (CI95%: 89,9- 94,3%), and therapeutic plan 97,9% (CI95%:96,7-99,1%). Patients
      declared as insatisfied gave high number of suggestions or showed more
      discrepancy of frequency (p<0.05); nevertheless, up to 28,9% of satisfied
      patients made suggestions for improving communication (p<0,001). CONCLUSIONS:
      [corrected] Designing open-ended questions where patient can make suggestions,
      seems to be a good method for detecting unmet needs in doctor patient
      communication that close-ended question about satisfaction or those exploring
      possible discrepancy on the frequency of some behaviours.

PMID- 21892557
TI  - Physical excercises on glycemic control in type 1 diabetes mellitus.
AB  - Type 1 diabetes is a metabolic diseases characterized by hyperglycemia, results
      from the destruction of insulin-producing pancreatic beta cells. Diabetes
      management usually by insulin, dietary and physical activity. AIM: Assess the
      relationship between physical activity and glycemic control in type 1 diabetes
      subjects. METHODS: The literature search conducted in Pubmed and ScienceDirect
      databases and was initially identified 24 articles and we applied the inclusion
      criteria that considered original, full-text, remaining thirteen articles
      published between 1992 and 2009. RESULTS AND DISCUSSION: Two studies found a
      positive association between physical exercises and adequacy of glycemic control
      on long-term, determining by glycated hemoglobin (HbAlc) and increase the insulin
      sensitivity, whereas three articles didn't found relations between exercises and
      glucose, insulin sensitivity and formation of ketone bodies. CONCLUSION: There
      are positive influences of exercise of long-term glycemic control in type 1
      diabetes, however results are contradictory with respect to insulin sensitivity
      and fasting glucose. Glycemic control in diabetes should be based on HbA1c
      values, self-monitoring of blood glucose and reduction of insulin requirement,
      such as have been demonstrated in several studies. Thus physical exercise, along
      with dietary therapy and medication, are important to control diabetes.

PMID- 21892558
TI  - Energy expenditure: components and evaluation methods.
AB  - INTRODUCTION: The determination of energy expenditure, considering the physical
      activity level and health status, is very important to adjust the individuals'
      nutritional supply. Energy expenditure can be determined by using indirect
      calorimetry, bioelectrical impedance, doubly labeled water, predictive equations,
      among others. All these methods have been used in clinical and research areas.
      However, considering the inconsistence in several research results, there is no
      consensus yet about the applicability of many of these methods. OBJECTIVES: The
      aim of this review is to describe the components of energy expenditure and the
      methods for its determination and estimation, summarizing their main advantages
      and limitations. RESULTS AND DISCUSSION: Indirect calorimetry and doubly labeled
      water are considered more accurate methods, but expensive. On the other hand,
      even though other methods present limitations, they are convenient and less
      expensive, and can be used with some caution.

PMID- 21892559
TI  - Molecular mechanisms of steatosis in nonalcoholic fatty liver disease.
AB  - Nonalcoholic fatty liver disease (NAFLD) is the most important cause of chronic
      liver disease and is considered the hepatic manifestation of the metabolic
      syndrome associated with diabetes mellitus type 2. The prevalence of NAFLD in the
      general population reaches 15-20%. It is also estimated that nonalcoholic
      steatohepatitis (NASH) affects 3% of the population. NAFLD refers to a wide
      spectrum of liver damage, which ranges from simple steatosis or intracellular
      triglyceride accumulation, to inflammation (NASH), fibrosis and cirrhosis. The
      mechanisms involved in the accumulation of triglycerides in the liver and
      subsequent hepatocellular damage are multifactorial and are not completely
      understood. However, metabolic changes such as insulin resistance (IR) are
      developed, being a common factor in the retention of fatty acids (FA) within the
      hepatocytes with oxidation and production of free radicals at the mitochondrial
      level, which are capable of causing lipid peroxidation, cytokine production, and
      necrosis. In addition, there are alterations in the hepatic bioavailability of
      long chain n-3 polyunsaturated fatty acids, conditions that alter the expression
      of a series of transcriptional factors involved in lipolytic and lipogenic
      processes in the liver. A greater knowledge of the etiopathogenic mechanisms of
      NAFLD is fundamental for the development of future effective therapeutic
      strategies. The pathophysiological fundamentals of liver steatosis are analyzed
      in this study.

PMID- 21892560
TI  - Systematic review of the clinical efficacy of sibutramine and orlistat in weigth
      loss, quality of life and its adverse effects in obese adolescents.
AB  - INTRODUCTION: The prevalence of obesity, a serious public health problem, is
      increasing among teenagers and thus also increases cardiovascular morbidity and
      mortality in adulthood. OBJECTIVE: To provide a systematic review of the best
      evidence about the effect of sibutramine and orlistat in weight loss, quality of
      life and its adverse effects in adolescents diagnosed with obesity. METHODS: We
      searched electronic databases and bibliographies of selected articles were
      inspected for any further reference. We included only randomized controlled
      trials that met a set of predefined criteria. The studies were reviewed by a
      narrative synthesis. RESULTS: We included 6 randomized controlled trials of
      sibutramine and 3 of orlistat. The majority reached a moderate to high
      methodological quality. Sibutramine and orlistat showed a reduction in body mass
      index (BMI) that was significantly higher compared with the placebo group. We
      also found a variation of weight with these drugs significantly better than
      placebo. Only one trial evaluated the quality of life. The incidence of adverse
      effects was similar for sibutramine and placebo, except for tachycardia. The most
      common adverse reactions associated with orlistat were gastrointestinal, mild to
      moderate. CONCLUSIONS: Sibutramine and orlistat in combination with a hypocaloric
      diet and changes in lifestyle in obese adolescents achieve a short-term loss of
      weight greater than that achieved through the dietary-behavioral therapy alone.

PMID- 21892561
TI  - Comparison of bioelectrical impedance with skinfold thickness and X-ray
      absorptiometry to measure body composition in HIV-infected with lipodistrophy.
AB  - INTRODUCTION: Human immunodeficiency virus (HIV)-associated lipodystrophy
      syndrome (LS) includes body composition and metabolic alterations. Lack of
      validated criteria and tools make difficult to evaluate body composition in this
      group. OBJECTIVE: The aim of the study was to compare different methods to
      evaluate body composition between Brazilians HIV subjects with (HIV+LIPO+) or
      without LS (HIV+LIPO-) and healthy subjects (Control). METHODS: in a cross
      sectional analyses, body composition was measured by bioelectrical impedance
      analysis (BIA), skinfold thickness (SF) and dual-energy x-ray absorptiometry
      (DXA) in 10 subjects from HIV+LIPO+ group; 22 subjects from HIV+LIPO- group and
      12 from Control group. RESULTS: There were no differences in age and body mass
      index (BMI) between groups. The fat mass (FM) (%) estimated by SF did not
      correlate with DXA in HIV+LIPO+ group (r = 0,46/ p > 0,05) and had fair agreement
      in both HIV groups (HIV+LIPO+ =0,35/ HIV+ LIPO- = 0,40). BIA had significant
      correlation in all groups (p < 0,05) and strong agreement, meanly in HIV groups,
      for FM (HIV+LIPO+ = 0,79/ HIV+LIPO- = 0,85 / Control = 0,60) and for fat free
      mass (FFM) (HIV+LIPO+ = 0,93 / HIV+LIPO- = 0,92 / Control = 0,73). DISCUSSION:
      Total fat mass can be measured by BIA with good precision, but not by SF in HIV
      infected patients with LS. Segmental BIA, triciptal SF, circumferences of arms,
      waist and legs maybe alternatives that need more studies.

PMID- 21892562
TI  - Comparison of NCHS, CDC and WHO growth charts in the nutritional assessment of
      hospitalized children up to five years old.
AB  - AIMS: This study evaluated the agreement of growth charts proposed by the
      National Center for Health Statistics (NCHS/1977), Centers for Disease Control
      and Prevention (CDC/2000) and World Health Organization (WHO/2006). METHODS: Were
      assessed children between 0 and 5 years old, hospitalized in the pediatric wards
      of a Brazilian school hospital. Z-score indexes: stature/age (S/A), weight/age
      (W/A) and weight/stature (W/S) was evaluated, in each of the three references
      (NCHS, CDC and WHO). ANOVA and test Bland & Altman and Lin plots were used in the
      comparison of the 3 charts. The agreement of the nutritional state categories was
      also evaluated, through kappa coefficient. The study was approved by the
      Institution's Research Ethics Committee. RESULTS: The study analyzed 337
      children, whose median age was 0.52 (IQR: 0.21-1.65) years, 65.3% of them were
      below 1 year old, 60.2% were male and 50% hospitalized due to acute respiratory
      disease. Lower Z-scores of W/A and S/A were obtained with the WHO charts and
      lower W/S with the CDC chart. High correlation and agreement were observed among
      the criteria, but more patients were classified as presenting shortness through
      the WHO criteria. CDC and WHO criteria were more rigorous than the NCHS criteria
      for the diagnosis of underweight (W/A) and malnutrition (W/S). CONCLUSION:
      Despite the strong agreement of the 3 charts, the adoption of the WHO charts
      seems to be more helpful for the children's nutritional screening for admission,
      as it enables to detect a higher number of malnourished children or at
      nutritional risk, who will benefit from an early intervention.

PMID- 21892563
TI  - [Agreement between the self-perception on the body image and the nutritional
      status in college students from Orense].
AB  - The aim of this study was to detect the possible changes in dietary behavior
      among college students from the University Campus of Orense by means of self
      perception of their body image. 145 college students participated, 107 women (74%
      of the study population with a mean age of 25.2 +/- 2.9 years) and 38 men (26%,
      with a mean age of 25.3 +/- 3.3 years). This is a descriptive cross-sectional
      study using questionnaires and assessing the body mass index (BMI), the
      subjective weight and using two sub-scales of the Eating Disorders Inventory 2:
      the body dissatisfaction (EDI-IC) sub-scale and the slimness obsession (EDI-OD)
      sub-scale. The results show that most of the population had normal weight, there
      exists no obesity among the female population and there were no underweight cases
      among the male population. More than half of the population (55% of women and 63%
      of men) that a distorted judgment of their body as compared to the BMI values,
      with men underestimating their weight and, among women, there are cases
      underestimating or overestimating their weight. The women more unsatisfied with
      their body image were those having overweight or low weight, and those more
      obsessed with losing weight are those in the upper limit of the normal weight.
      Among men, those having overweight or obesity are the most unsatisfied and most
      obsessed with losing weight.

PMID- 21892564
TI  - Agreement and association between the phase angle and parameters of nutritional
      status assessment in surgical patients.
AB  - BACKGROUND & AIMS: To assess the agreement and the association between phase
      angle (PA) and parameters of nutritional status in surgical patients. METHODS:
      This was a cross-sectional study that involved 98 patients admitted for elective
      gastrointestinal or hernia repair surgery. The risk and nutritional status were
      evaluated through Nutritional Risk Screening 2002 (NRS 2002), Subjective Global
      Assessment (SGA), Body Mass Index (BMI) and Total Lymphocytes Count (TLC). These
      assessments were compared with the mean standardized PA (SPA), obtained by
      Bioelectrical Impedance Analysis (BIA). Statistical analysis included kappa
      coefficient, Student's t-test, Mann-Whitney test, and the construction of a ROC
      Curve. RESULTS: The highest kappa agreement was obtained between the SPA and the
      SGA (0.27; CI95% 0.06-0.48). Malnourished patients diagnosed by NRS 2002, SGA and
      TLC had a significantly lower mean SPA as compared to those who were well
      nourished. A cut-off point of 0.8 for SPA showed 82.6% (CI95% 65.0-100.0%)
      sensitivity and 40.6% (CI95% 23.0-58.2%) specificity. CONCLUSION: The SPA
      presented weak agreement with the methods of nutritional assessment, as well as
      low specificity, and could not be recommended as a marker of nutritional status,
      despite the fact that the lowest values for SPA were found in malnourished
      patients.

PMID- 21892565
TI  - Determination of temperature variation during the individual steps of the
      production of hospital diets of modified consistency.
AB  - BACKGROUND & AIM: Many disease outbreaks of food origin are caused by foods
      prepared in Food Service and Nutrition Units of hospitals, affecting hospitalized
      patients who, in most cases, are immunocompromised and therefore at a higher risk
      of severe worsening of their clinical status. The aim of this study was to
      determine the variations in temperature and the time-temperature factor of
      hospital diets. METHODS: The time and temperature for the preparation of 4 diets
      of modified consistency were determined on 5 nonconsecutive days in a hospital
      Diet and Nutrition Unit at the end of preparation and during the maintenance
      period, portioning and distribution at 3 sites, i.e., the first, the middle and
      the last to receive the diets. RESULTS AND DISCUSSION: All foods reached an
      adequate temperature at the end of cooking, but temperature varied significantly
      from the maintenance period to the final distribution, characterizing critical
      periods for microorganism proliferation. During holding, temperatures that
      presented a risk were reached by 16.7% of the meats and 59% of the salads of the
      general diet, by 16.7% of the garnishes in the bland diet and by 20% of the meats
      and garnishes in the viscous diet. The same occurred at the end of distribution
      for 100% of the hot samples and of the salads and for 61% of the desserts. None
      of the preparations remained at risk temperature for a time exceeding that
      established by law. CONCLUSION: The exposure to inadequate temperature did not
      last long enough to pose risks to the patient.

PMID- 21892566
TI  - Dynamics of the components of energy intake between Spanish and Mexican preschool
      children: energy density and food volume in two contexts.
AB  - OBJECTIVE: To determine the differences in the dynamics of dietary energy density
      (ED), food volume (FV) and energy intake (EI) between two groups of healthy
      children, in normal conditions, from Spain and Mexico. METHODS: Crossectional
      study which analyses the habitual diet of two healthy children groups, 1-4 years
      old, from Reus (Spain, n = 203) and Guadalajara (Mexico, n = 147). Dietary intake
      was assessed using the 24-hour recall. Anthropometric data were also obtained. We
      estimated Z-score of weight, height and BMI, and EI (kcal/day), ED (kcal/g), FV
      (g/day), El/kg body weight (kcal/kg/day) and FV/kg body weight (g/kg/day).
      RESULTS: The Spanish children consumed significantly more cereals (p < 0.05),
      vegetables, meat, fish and eggs than the Mexican children (p < 0.001), while the
      latter consumed significantly more sweets (p < 0.001). The mean El/kg body weight
      was 107.7 +/- 36.2 kcal/kg/day in the children from Reus, and 102.4 +/- 38.8
      kcal/kg/day in the children from Guadalajara, without significant differences.
      While the ED was significantly higher (p < 0.001) in the Spanish sample (1.41 +/-
      0.35 kcal/g) that in the Mexican one (1.19 +/- 0.37 kcal/g), we observed the
      contrary on FV per kilogram of weight: it was significantly (p < 0.001) greater
      in Mexicans (91.0 +/- 36.1 g/kg/day) than in Spanish (79.5 +/- 27.5 g/kg/day).
      CONCLUSION: In two populations with different contexts, the balance between
      energy intake and energy requirements is achieved in different ways, allowing
      energy intake per unit of weight and growth to be adequate. Future studies are
      needed to clarify the factors of a possible alteration of this equilibrium
      through time, in such a way, that it would probably contribute to the development
      of overweight and obesity in several environments.

PMID- 21892567
TI  - [Oropharyngeal dysphagia in elderly inpatients in a unit of convalescence].
AB  - MAIN OBJECTIVE: To describe the prevalence of oropharyngeal dysphagia at hospital
      discharge in elderly patients admitted to a Subacute Care Unit (SACU) using the
      Volume-Viscosity Swalow Test (V-VST) and an adapted version for severe dementia
      (V-VST-G). METHODOLOGY AND DESIGN: Descriptive cross-sectional study; duration;
      50 days. Data gathered from the clinical chart at hospital discharge:
      demographical, clinical, risk factors, and complications of dysphagia, functional
      course, and V-VCAM and V-VCAM-G outcomes. The results are described comparing the
      data of the groups with and without dysphagia. RESULTS: 86 Patients (60% women),
      mean age 83.8 +/- 6.7 years. The specific clinical history detected previous
      oropharyngeal dysphagia in 23 patients (26%). The V-VCAM detected oropharyngeal
      dysphagia in 46 patients (53.5%). Of them, 30 patients (65.21%) had mixed
      swallowing disorder, 15 (32.6%) had isolated efficacy disorder, and 1 (2.17%) had
      isolated safety disorder. Those patients with a positive dysphagia test had a
      statistically significant higher prevalence of cognitive disorder, higher age,
      and more positive history of previous dysphagia, worse functional course and
      mobility impairment, and more complications during their staying at the SACU.
      CONCLUSIONS: Dysphagia is highly prevalent among this group of elderly patients.
      Only half of the cases are diagnosed through the specific anamnesis. The V-VCAM
      detected a high prevalence of dysphagia so that its routine use is recommended
      specially in patients at risk taking into account the peculiarities of using it
      in the elderly. This at-risk population would be defined by characteristics such
      as higher age, cognitive and/or functional impairment.

PMID- 21892568
TI  - [Nitrogen and protein content analysis of human milk, diurnality vs
      nocturnality].
AB  - Breast milk is changing with the progression of lactation and during a 24-h
      period. To determine the effect of diurnality or nocturnality on total nitrogen
      and protein content of the breast milk. We collected human milk samples from
      health mothers living throughout Community of Extremadura (Spain) from January
      2008 to December 2008 with less than two months of lactation. We divided the
      samples in three groups: calostral group (1-5 days postpartum), transitional
      group (6-15 days postpartum) and mature group (> 15 days postpartum). All samples
      were stored in a freezer at -80 oC. We considered as day period between 08:00
      20:00 h and night period 20:00-08:00 h. Analysis of the human milk samples was
      based on the Kjeldahl method. Protein contents were calculated from total
      nitrogen x 6,25. The statistical analysis of the data was descriptive (mean +/-
      standard deviation) and inferential (T-Student test). No differences (P > 0,05)
      were found to exist among the contents of individual human milk samples. The mean
      contents of each component were as follows: Total nitrogen of calostral,
      transitional and mature group was 0,30 +/- 0,06 g/dL (night period), 0,29 +/-
      0,05 g/dL (day period); 0,26 +/- 0,04 g/dL (night period), 0,25 +/- 0,04 g/dL
      (day period); 0,22 +/- 0,05 g/dL (night period), 0,20 +/- 0,04 g/dL (day period)
      respectively, in this mature group with a statistical variation (P < 0,05).
      Protein content of calostral, transitional and mature group was 1,88 +/- 0,4 g/dL
      (night period), 1,81 +/- 0,3 g/dL (day period); 1,62 +/- 0,3 g/dL (night period),
      1,59 +/- 0,3 g/dL (day period); 1,35 +/- 0,3 g/dL (night period), 1,26 +/- 0,3
      g/dL (day period) respectively, in this mature group with a statistical variation
      (P < 0,05). Although we observed differences in the nitrogen and protein content
      during the individual stages of lactation, it is just in the population of mature
      lactating women, where the components analyzed varied significantly between day
      and night.

PMID- 21892569
TI  - [Effect of nutritional support on survival in patients with amyotrophic lateral
      sclerosis].
AB  - INTRODUCTION: Malnutrition affects morbidity and mortality of patients with ALS.
      The nutrition unit should evaluate these patients early and regularly providing
      the necessary steps in the evolution of the disease. METHODS: A retrospective
      cohort study in which we analyzed 46 patients diagnosed with ALS, 21 of them
      received nutritional therapy. We studied age, mode of onset, date of entry into a
      nutritional protocol, placement of PEG and survival. We performed a test of
      Breslow comparing patients who were at nutritional protocol with those not
      receiving nutritional support, and those who received early nutritional therapy
      with those with delayed nutrition. RESULTS: There was an increase in median
      survival for patients in nutritional therapy in bulbar ALS (452 vs 55 days) and
      in spinal ALS (1,798 vs 357 days) (p = 0.002). The median delay in the initiation
      of nutritional therapy in spinal ALS was 557 days while in bulbar ALS was 230
      days. The survival in the spinal ALS of those who entered into nutritional
      protocol before the median survival was 325 days to 181 days (p = 0.09) while in
      bulbar ALS those who entered before had a median survival of 435 days to 177 days
      (p = 0.38). CONCLUSIONS: The entry of patients with ALS in a nutritional protocol
      increases survival. There is an advantage in the evolution of patients with early
      nutritional treatment.

PMID- 21892570
TI  - [Stability study of paediatric extemporaneous parenteral nutrition with lipids].
AB  - Stability of extemporaneous parenteral nutrition is a critical aspect of these
      formulations, with impact in patient safety and quality of service. In lipid
      emulsions physical stability can be assessed by the increase in the number of
      lipid globules of size superior than 500 nm, generated by coalescence of small
      globules during time. OBJECTIVES: To determine medium size of the lipid globules
      that compose the internal phase of TNA, in order to evaluate its stability and
      establish beyond-use date of the parenteral nutrition. To evaluate distribution
      profile of the lipid globules in the parenteral nutrition and compare it with
      this of the lipid emulsion used as raw material. METHOD: Globule size assessment
      by dynamic light scattering in a paediatric extemporaneous parenteral nutrition
      formula of frequent use, stored in different periods of time and temperatures.
      RESULTS: Medium globule size of the parenteral nutrition analyzed samples did not
      exceed the limit recommended by literature. Medium size and distribution of the
      lipid globules in the original lipid emulsion did not have significative changes
      after the compounding of the parenteral nutrition. DISCUSSION: Obtained data
      allow to consider that the extemporaneous parenteral nutrition evaluated would
      have a beyond-use date superior than the one now in use. This research must be
      deepened by the study of other formulas of parenteral nutrition in order to
      optimize the setting of beyond-use date.

PMID- 21892571
TI  - Factors associated with oxidative stress in women with breast cancer.
AB  - OBJECTIVE: To assess the association between physiological, physical, lifestyle
      and nutritional variables and oxidative stress biomarkers in women with breast
      cancer. METHODS: This cross-sectional study was conducted on 55 women newly
      diagnosed with breast cancer. The extent of oxidative stress was analyzed by the
      measurement of plasma lipid hydroperoxides (LH), thiobarbituric acid reactive
      substances (TBARS), protein carbonyl, whole blood reduced glutathione (GSH) and
      serum antioxidant capacity (AC). Diet data were obtained from food frequency
      questionnaire. Linear regression was used to determine the association between
      the variables studied and oxidative stress biomarkers. The protein carbonyl data
      was not included in the linear regression analyses since the data did not show a
      normal distribution, even after logarithmic and other transformations. RESULTS:
      After adjusting for energy intake, the intake of chicken and high-fat dairy
      products was associated with increased levels of LH, while vitamin E intake was
      associated with decreased LH levels (R2 = 23.8%). Intake of oils was associated
      with increased levels of TBARS (R2 = 6.82%). Positive axillary lymph node status
      was associated with decreased levels of GSH (R2 = 9.31%). Increasing age was
      directly associated with levels of AC, while animal fat, dairy product, and sweet
      food intakes were associated with low levels of AC (R2 = 41.42%). CONCLUSION:
      Intake of chicken, vitamin E, dairy products (particularly high-fat dairy
      products), oils, animal fat, and sweet foods, along with axillary lymph node
      status and age, may be important determinants of oxidative stress in women with
      breast cancer.

PMID- 21892573
TI  - Glycemic acute changes in type 2 diabetics caused by low and high glycemic index
      diets.
AB  - INTRODUCTION: Low-glycemic index diets may improve the glycemic control in type 2
      diabetes but the debate over their effectiveness continues. OBJECTIVES: To test
      the effects of low-glycemic index diets on acute glycemic control (2 days) by
      measuring capillary blood glucose in patients with type 2 diabetes. METHODS: This
      was a crossover randomized clinical trial with 12 type 2 diabetics which were
      randomly divided into 2 groups and targeted the following draft diets for low and
      high glycemic index (LGI and HGI) for 2 consecutive days in 2 consecutive weeks.
      Group 1 followed an LGI diet in week 1 and an HGI diet in week 2, group 2 adopted
      the contrary. They were oriented to maintain medication and lifestyle and to
      follow the recommendations. Measurements were made of glycemia capillaries in 2
      days (fasting, before lunch, post-prandial lunch and before dinner) and one last
      in fasting on day 3. A food record during the days and the counting of
      carbohydrates meals was made. The software SigmaStat (version 2.03) was used,
      with a statistical significance criterion of p < 0.05. RESULTS AND DISCUSSION:
      The amount of carbohydrates ingested by the LGI group was lower (p < 0.01),
      showing that the adoption of this diet reduces the intake of carbohydrates, being
      favorable for diabetics. Mean blood glucose on the first day was lower in the LGI
      group (p < 0.05).

PMID- 21892572
TI  - [Incidence of nutritional support complications in critical patients: multicenter
      study].
AB  - INTRODUCTION: Nutritional support (NS) leads complications that must be detected
      and prompt treated. OBJECTIVE: To estimate the incidence of some complications of
      nutritional support in critically ill patients. MATERIALS AND METHODS: A
      multicenter, descriptive, prospective study in patients with NS in intensive care
      units. Studied variables included medical diagnosis, nutritional status, length
      of NS, path, type of formula and ten complications. RESULTS: 419 patients
      evaluated, 380 received enteral nutrition (EN) and 39 parenteral nutrition (PN).
      The high gastric residue was the most incident complication in the ENS (24.2%),
      followed by diarrhea (14%) and withdrawal tube (6.6%). The high gastric residue
      and diarrhea were associated with the duration of the NS (p < 0.05). For the PNS
      the complication most incidents were hypophosphatemia (38.5%), followed by
      catheter sepsis (15.4%). The duration of the NS was associated with cholestasis,
      sepsis and hypophosphatemia (p < 0.05). CONCLUSIONS: complications of highest
      incidence were the high gastric residue for EN and hypophosphatemia for the PN;
      the withdrawal of the tube is a complication that claims further monitoring. The
      duration of the NS was the variable that showed greater association with the
      complications studied. Is a must to get consensus on complications definitions
      for comparisons establishment and best international standards target,
      furthermore propose protocols in order to decrease complications incidence of NS
      to fulfill the critical ill patient requirements.

PMID- 21892574
TI  - Lipid profile and cardiovascular risk factors among first-year Brazilian
      university students in Sao Paulo.
AB  - BACKGROUND/AIMS: The surveillance of cardiovascular risk factors has been
      recommended worldwide. The current study is aimed to estimate the prevalence of
      cardiovascular risk factors among first-year students from a public university in
      the city of Sao Paulo, Brazil. METHODS: A cross-sectional study of 56 first-year
      students, of both genders, was performed. Information about demographic
      characteristics, family history of chronic diseases, smoking, and physical
      activity was obtained by means of a standardised questionnaire. Anthropometrical
      parameters (BMI, waist circumference, body fat percentage), metabolic parameters
      (glycaemia, serum lipid profile), and dietary data (total energy intake,
      percentage of total energy from macronutrients, cholesterol and dietary fiber)
      were assessed. RESULTS: The risk of cardiovascular diseases was characterised by
      family history of cardiovascular diseases (44.6%), smoking (10.7%), physical
      inactivity (35.7%), borderline high total cholesterol and LDL-c levels (16.1% and
      5.4, respectively), decreased HDL-c levels (8.9%), increased triglyceride levels
      (8.9%), and overweight and obesity (17.8% and 7.1%, respectively). The diet of
      the students was inadequate: it was high in fat and protein, and low in
      carbohydrate and dietary fibre. CONCLUSIONS: The prevalence of risk factors for
      cardiovascular diseases in young adults draws attention to the need to adopt
      preventive plans in the university setting.

PMID- 21892575
TI  - [Changes on dietary habits of the late-breakfast in a school population].
AB  - BACKGROUND: The establishment of healthy eating habits in children at school and
      in family life is very important for preventing obesity in children. AIMS: To
      know the habits of late-breakfast in a scholar population, the prevalence of
      overweight and obesity, and establish healthy dietary habits through the late
      breakfast. METHODS: A prospective interventional study was performed in a school
      group. Children from 10 to 13 years-old were included. The study had three
      phases: pre-intervention (anthropometric assessment and questionnaire of late
      breakfast frequency), intervention (parents and teachers received information
      about "the importance of proper nutrition in school" focused on the transcendence
      of a healthy and balanced diet that includes a suitable late-breakfast every day
      at school, and the students received the late-breakfast during two weeks that
      included milk, fruit and a traditional sandwich), and post-intervention
      (questionnaire of late-breakfast frequency). RESULTS: Frequency of overweight was
      10.6% and obesity 2.6%. After the intervention the proportion of children who had
      late-breakfast increased by 9.2%, and the kind of food which they ate changed.
      CONCLUSION: Dietary habits can be modified in a scholar population with an easy
      nutritional intervention.

PMID- 21892576
TI  - [Micronutrient supplementation in parenteral nutrition in Spanish hospitals].
AB  - Several years ago, it was recommended not to add vitamins or oligoelements to
      parenteral nutrition (PN) solutions and to administer them immediately after the
      addition of the micronutrients to avoid their decay. Nowadays, it has been
      observed that with multilayer bags, ternary mixtures and sunlight protection
      vitamins degradation is minimal. Daily intake of micronutrients is necessary in
      the critically ill, malnourished or long-term PN patients. Aiming at knowing the
      schedules of use of micronutrients in PN in Spanish hospitals and the way PN bags
      are prepared regarding the factors conditioning their stability, we undertook a
      telephone survey to the pharmacists in charge of PN at the different hospitals.
      We compared the data obtained with those from other surveys performed in 2001 and
      2003. Pharmacists from 97 hospitals answered the questionnaire (answer rate 88%).
      The hospital sizes ranged 104-1728 beds. As compared to the data form preceding
      years, we observed a better adequacy to the current recommendations, although
      there are still 30% of the hospitals that administer micronutrients on an every
      other day basis independent of the clinical situation of the patients. In most of
      the hospitals, multilayer bags are used and/or sunlight protection and ternary
      mixtures. According to these results showing the different criteria for
      administering vitamins and oligoelements in PN solutions, it seems necessary to
      elaborate consensus documents that adapt to the reality of the diverse practices
      besides promoting the performance of well-designed clinical studies establishing
      the requirements under special clinical situations.

PMID- 21892577
TI  - Percentile values for aerobic performance running/walking field tests in children
      aged 6 to 17 years: influence of weight status.
AB  - The aim of this study was to provide percentiles values for four different
      aerobic performance tests in 2752 (1,261 girls) Spanish children aged 6 to 17.9
      years. Aerobic performance was assessed by the shuttle run test (20 mSRT), 1
      mile, 1/2-mile and 1/4-mile run/walk tests. Height and weight were measured, and
      body mass index was calculated. Boys had significantly better score than girls in
      the studied tests in all age groups, except in 1/4-mile test in 6-7 year old
      children. Underweight children had similar performance than their normalweight
      counterparts, and underweight boys had better performance than their obese
      counterparts. Overweight and obese children had lower performance than their
      normalweight counterparts. Having percentile values of the most used field tests
      to measure aerobic performance in youth may help to identify children and
      adolescents at risk for the major chronic diseases, as well as to evaluate the
      effects of alternative interventions.

PMID- 21892578
TI  - [Home-Based Parenteral Nutrition (HBPN)-associated hepatobiliary complications].
AB  - Home-based parenteral nutrition (HBPN) allows recovering or maintaining the
      nutritional status of patients with chronic intestinal failure that cannot afford
      their nutritional requirements through the digestive route. Frequently, liver
      function impairments develop along the treatment, which in the most severe cases,
      and especially in premature and low-weight infants, may lead to an irreversible
      liver failure. The proper composition of the parenteral nutrition bag, avoiding
      an excess of energy intake, together with the use of new types of lipid emulsions
      (with lower content in -6 fatty acids and voided of phytosterols) as well as the
      use, although being minimal, of the enteral route, may contribute to a decrease
      in the occurrence of HBPN-associated liver disease. It is necessary to perform
      monthly clinical and biochemical checks to early detect liver function
      impairments in order to perform the appropriate changes in the treatment and
      assess the indication of a potential bowel transplant before the liver damage
      becomes irreversible.

PMID- 21892579
TI  - Increased resting energy expenditure by fat-free mass in children and teenagers
      with constitutional leanness.
AB  - BACKGROUND/OBJECTIVES: To compare the resting energy expenditure (REE) and the
      REE/Fat-free-mass (FFM) quotient in children with constitutional leanness (CL)
      and children with normal body weight, and to describe the within-family
      clustering of CL. SUBJECTS/METHODS: We have studied 18 children and teenagers
      with CL, 10 girls and 8 boys, and 18 gender and age matched normal controls, with
      the same pubertal stage. All were recruited from the outpatient pediatric clinic
      nutrition unit. None of the children with CL showed symptoms of chronic illness,
      they had normal laboratory results, they had a normal caloric food intake, and
      they did not agree with the DSM-IV-TR criteria for anorexia nervosa. We describe
      the body mass index (BMI) of children and their parents. The children were
      classified according to Cole's recently published BMI cut-offs for thinness:
      under 18.5 points in CL group, stable at least in the last year, and between 18.5
      and 25 cutt-offs in the control group. The body composition was calculated by
      anthropometric methods (skinfold thickness measurements). In addition REE was
      measured using fasting indirect calorimetry. RESULTS: The CL group had a higher
      mean percentage of FFM, and a mean FM significantly less, relative to controls (p
      < 0.001). The average absolute REE was significantly lower in the CL group
      (1,106.55 +/- 240.72 kcal) than the control group (1,353.33 +/- 270.01 kcal/dia)
      (p < 0.01). However, the REE adjusted for FFM showed a mean significantly greater
      in the CL group (41.39 +/- 2.26 kcal/kg FFM) (Mean confidence interval (CI) 95 %:
      40.33-42.45) than the controls (37.37 +/- 3.06 kcal/kg FFM) (Mean CI 95 %: 35.93
      38.81) (p < 0.001). Finally, in the family study, the mean BMI of fathers of CL
      group was significantly lower (p < 0.01), but there were not any differences in
      the mean BMI of mothers. Among parents with BMI known, 8 of 35 parents of CL
      group had an BMI lower 18.5, and only 2 of 36 parents in the control group (p <
      0.05). CONCLUSIONS: This increased energy expenditure-to-FFM ratio differentiates
      between CL and controls. These metabolic differences are probably genetically
      determined.

PMID- 21892580
TI  - The use of biochemical and immunological parameters in nutritional screening and
      assessment.
AB  - OBJECTIVE: To evaluate the relationship between serum albumin, total cholesterol
      and total lymphocyte count with two nutritional assessment methods, to verify if
      their use is justified in nutritional screening tools. METHODS: 101 patients
      admitted to medical/surgical wards underwent the SGA and the Full Nutritional
      Assessment (FNA). Blood test which included serum albumin, total cholesterol and
      total lymphocyte count (TLC), were made. Percentage of weight loss and BMI were
      calculated. An Anova test was done to measure the differences in the mean levels
      of the three parameters for the nutritional status evaluated by SGA and FNA. The
      probability of a patient being malnourished in the four ranges established for
      each parameter was calculated, as well as the relationship between the ranges and
      the percentage of weight loss and BMI. Sensitivity and specificity were
      calculated and the corresponding ROC curves, using SGA as gold standard. RESULTS:
      Prevalence of undernutrition is 43.6% and 44.6% for SGA and FNA respectively.
      Mean levels of the three parameters decrease as the undernutrition degree
      increases (p < 0.005 for all cases). The probability of a patient being
      malnourished gets higher as parameter lowers (p = 0.000 for all cases). Total
      cholesterol shows a relationship with BMI < 18.5 and presence/absence of weight
      loss (p = 0.074 and p = 0.002 respectively). The area under ROC curves are
      albumin (0.823), cholesterol (0.790) and TLC (0.758) respectively. CONCLUSIONS:
      The analytical parameters analyzed show a statistically significant relationship
      with the nutritional status. Therefore, they are suitable for use in nutritional
      screening.

PMID- 21892581
TI  - [Adherence to a Mediterranean diet in a college population].
AB  - OBJECTIVE: To determine the adherence to the Mediterranean diet of a university
      population and to analyze several factors that may condition its nutritional
      quality. MATERIAL AND METHODS: Distribution of the Kidmed test to a random sample
      of 570 university students. The Kidmed index (0-12) indicated whether the
      adherence to the Mediterranean diet was low (0-3), intermediate (4-7) or high (8
      12). The gender, age, weight, height, and body mass index were gathered from each
      participant, as well as the type of residence and the province of origin.
      RESULTS: The sample comprised 217 men and 353 women aged 18-25 years. 9.5% of the
      university students had a low Kidmed index, 62.1% intermediate, and 28.4% high.
      Those students living at their parental home had a high percentage of adherence
      (35.6%), significantly higher (p < 0.05) to that of those living at a student's
      residence (11.1%) or at a student's apartment (11.2%). Overweighed students had a
      low percentage of adherence (15.5%), significantly higher (p < 0.05) to those
      with a normal nutritional situation (8.5%). CONCLUSIONS: 71.6% of university
      students need to improve their dietary pattern (low to intermediate adherence to
      the Mediterranean diet), and we could observe a certain family factor of
      preservation of the traditional dietary habits. Those university students with
      low adherence had a higher risk for being overweighed. It would be convenient to
      develop nutritional education programs in the university curricula.

PMID- 21892582
TI  - [Comparative analysis of vitamin D status and solar exposition habits in
      adolescent and elderly Spanish women. The Five Countries Study (OPTIFORD
      Project)].
AB  - INTRODUCTION: Vitamin D deficiency is known to be very common in adolescent girls
      and elderly women. AIM: To analyze vitamin D status, vitamin D intake and solar
      exposure of Spanish participants in The Five Countries Study of Optiford Project.
      METHODS: Questionnaires approved and validated of lifestyle and food consumption
      frequency applied. The biochemical analysis of 25-hidroxivitamin D and PTH and
      the evaluation of the solar exposure (dosymeter UV VioSpor) were carried out.
      RESULTS: The average solar exposure of adolescent girls (1,519 J/m2) was double
      than elderly women (740 J/m2). The vitamin D status of adolescent girls in summer
      and winter was better than elderly women. CONCLUSIONS: Solar exposure habits are
      different between the two age groups. This fact, jointly to the lower body's
      capacity to synthesize Vitamin D through exposure to the sun in the elderly, may
      justify the worse vitamin D status in this age group.

PMID- 21892583
TI  - Mineral and/or milk supplementation of fruit beverages helps in the prevention of
      H2O2-induced oxidative stress in Caco-2 cells.
AB  - INTRODUCTION: Fruit beverages are commonly supplemented with milk, vitamins
      and/or minerals in order to improve their healthy effects by providing some
      bioactive components that can act additively or synergistically against oxidative
      stress. AIMS: To test whether iron, zinc, and milk added to fruit beverages do
      not affect the cytoprotective effect against oxidative damage to Caco-2 cells
      through GSH-related enzymes induction and cell cycle progression preservation, in
      comparison with non-supplemented fruit beverage. METHODS: Caco-2 cells were
      incubated 24 h with the bioaccessible fraction (BF) of eight fruit beverages
      with/without iron and/or zinc, and/or milk, and then challenged with H2O2 (5 mmol
      L-1 -2 h). Mitochondrial enzyme activities (MTT test), GSH-Rd and GSH-Px enzyme
      activities, cell cycle progression and caspase-3 activity were measured. RESULTS
      AND DISCUSSION: Fruit beverages prevented the deleterious effect of H2O2 on cell
      viability, with almost all samples reaching control basal levels. Only
      independent iron or zinc supplementation with/without milk exerted positive
      effects upon GSH-Rd activity. Both minerals with milk, afforded improved
      preservation of GSH-Px activity. All samples prevented the decrease in the G1
      phase of cell cycle induced by H2O2, except iron supplemented samples
      with/without milk, but none of them avoided the increase in sub-G1 phase.
      However, this fact was not associated to caspase-3 activity, with a probable
      positive effect of zinc upon this parameter. CONCLUSION: Mineral and/or milk
      supplementation of fruit beverages helps in the prevention of oxidative stress in
      Caco-2 cells based on cell viability maintenance, GSH-related enzymes activation,
      cell cycle distribution preservation and inhibition of caspase-3 activation.

PMID- 21892584
TI  - [Blood glucose levels in the first 24 hours of admission is not a risk factor for
      mortality in critical care patients].
AB  - INTRODUCTION: Glycemic alterations are known as a risk condition of death in
      several diseases, such as ischemic cardiovascular and neurological disorders. The
      fact that its tight control under narrow normality levels decreases mortality and
      morbidity have led to further studies seeking to confirm the results and expand
      them to other disease areas. OBJECTIVES: To determine whether glycemic changes by
      themselves are a mortality risk factor in a sample of patients within an
      Intensive Care Unit (ICU), among which predominates traumatic-surgical patients.
      METHODS: Demographic and analytical characteristics were revised, as well as
      common monitoring variables in an ICU, among a sample of 2,554 patients from
      admissions between 1st January 2004 and 31 December 2008. Data were obtained from
      a database which endorsed records compiled with the monitoring ICU patients
      program "Carevue". They were processed with dynamics sheets included in the Excel
      software with the following variables: initial glycemia, mean glycemia during the
      first 24 hours and number of determinations performed. We used the mean value in
      the admission day of the remaining analytical and monitoring variables and the
      number of test performed on this first day. The sample was stratified in two
      groups for the statistical analysis: a) General Sample (MG) and b) sample
      excluding patients admitted after a programmed surgery (EQP). In both cases the
      effect of initial and averaged glycemia was checked. Group b was divided in two,
      according to the number of determinations b1) a single blood glucose
      determination group (EQP1) and b2) a multiple determination group (EQPM). From
      this group of non-programmed surgical patients the study was repeated in those
      patients who stayed at the ICU 3 or more days (EQP3D). Chi-square and Mantel
      Haenzel test for the ODD ratio determination were performed for qualitative
      variables; quantitative variables were examined with the Mann-Whitney test. At
      each analysis level, logistic regression was performed using mortality as the
      dependent variable, including those variables with p-values < 0.05 which
      represented more than 60% of the data. An initially saturated model with backward
      till the final equation was used. A p-value of 0.05 (i.e. p < 0.05) was set as
      the significant threshold for all statistical analysis. They were performed with
      SPSS and GSTAT 2 statistical software. RESULTS AND DISCUSSION: A total of 2,165
      of the 2,554 admitted patients during the study period were included (96.5%).
      Exclusion criteria were absence of plasma glucose determinations. In the
      bivariate analysis, first and mean glucose blood levels showed significant
      differences in mortality rates in absolute figures and also when data were
      classified stratified in three levels (< 60 mg/dl; 60-110 mg/dl or > 110 mg/dl)
      or in two (normal values 60 to 110 mg/dl and unusual figures < 60 mg/dl or > 110
      mg/dl). These significant differences were lost when a logistic model was
      applied. From the remaining variables, renal function and NEMS showed to be
      mortality risks factors in this sample. CONCLUSIONS: Hyperglycemia is a
      predominant phenomenon in critically ill patients. Hypoglycemia is less frequent
      and is associated with higher mortality rates. Initial glucose blood level, by
      itself, was not a mortality risk factor in the multivariate study and at none of
      the studied levels. Average glycemia did not add any prediction power. The
      changes in glucose blood levels seemed to be an adaptation process, which
      determined by itself a risk for the patient's discharge, at least in the first 24
      hours period after ICU admission.

PMID- 21892585
TI  - [Obesity in a school children population from Granada: assessment of the efficacy
      of an educational intervention].
AB  - OBJECTIVES: The objective of this research was to study the prevalence of obesity
      and excess weight in a population of school children and adolescents, and to
      verify the effectiveness of an educational intervention, as reflected in the
      variation of their body mass index values. MATERIALS: The population sample was
      composed of 977 school children and adolescents from 9 to 17 years of age,
      belonging to 13 public elementary schools and high schools in the city and
      province of Granada (Spain). METHODOLOGY: This longitudinal cohort study was
      analytical, muticentric, and observational. It was carried out in three phases.
      The first phase involved the evaluation of the nutritional state of the sample
      population by means of anthropometric measurements (weight, height, body mass
      index, six skin folds and four body perimeters) as well as arterial blood
      pressure. The second phase entailed an educational intervention focusing on good
      nutritional habits and physical exercise. The third and final phase evaluated the
      effectiveness of the intervention. RESULTS: A higher obesity prevalence (15.1%)
      was found in school girls between 12 and 13. In the case of boys, obesity
      prevalence was lower up to age 13 though afterwards, it progressively increased
      (12.6%). The educational intervention produced an important reduction in body
      mass index values in both sexes though this reduction was more significant in
      young females. CONCLUSIONS: There is a currently an alarming increase in obesity
      and overweight prevalence among the population evaluated in this study. The
      significant reduction in body mass index values resulting from this research
      confirmed the effectiveness of the educational intervention to reduce excess
      weight.

PMID- 21892586
TI  - [Consumption of the probiotic Lactobacillus planctarum CECT 7315/7316 improves
      general health in the elderly subjects].
AB  - INTRODUCTION: Ageing induces changes in gut microbiota that may affect the
      quality of life. In this work we analyze the effect of Lactobacillus plantarum
      CECT 7315/7316 on the regulation of intestinal transit and on nutritional status.
      METHODS: We carried out a double-blind, randomized and controlled by placebo
      clinical trial. We evaluated the evolution of the weekly defecation frequency and
      blood levels of total proteins, albumin, cholesterol and reactive C-protein.
      RESULTS: Lactobacillus plantarum CECT 7315/7316 helps to regulate intestinal
      transit and improves the nutritional status in elderly. CONCLUSIONS: Consumption
      of functional foods containing L. plantarum CECT 7315/7316 improves the quality
      of life in elderly subjects.

PMID- 21892587
TI  - [Wilkie syndrome: report of a case].
AB  - Wilkie syndrome is an unusual form of high gastrointestinal obstruction resulting
      from compression of the duodenum between the abdominal aorta and the superior
      mesenteric artery (SMA). The conditions that cause this syndrome can be
      classified into five categories: severe wasting diseases, severe injuries,
      diseases, deformity or trauma to the spine, dietary disorders and posoperative
      state. The symptoms include nausea, vomiting, distention postprandrial,
      epigastric pain and weight loss. Barium meal and arteriography were used as
      diagnostic tools, now CT-angiography is being used and shown higher diagnostic
      sensitivity. The diagnostic criteria are: dilated duodenum, compression of the
      duodenum by the SMA and aortomesenteric angle <20 degrees. Patients with acute
      syndrome often respond to conservative treatment (decompression, correction of
      dehydration and electrolyte imbalance and nutrition support). Most of the
      patients with chronic syndrome require surgical intervention. Duodenojejunostomy
      is the most effective surgical option, with a success rate of 90%.

PMID- 21892588
TI  - Biomarkers of metabolic syndrome and its relationship with the zinc nutritional
      status in obese women.
AB  - INTRODUCTION: Obesity is a chronic disease that induces risk factors for
      metabolic syndrome and, is associated with disturbances in the metabolism of the
      zinc. Therefore, the aim of this study was to investigate the existence of
      relationship between the biomarkers of metabolic syndrome and the zinc
      nutricional status in obese women. METHOD: Seventy-three premenopausal women,
      aged between 20 and 50 years, were divided into two groups: case group, composed
      of obese (n = 37) and control group, composed of no obese (n = 36). The
      assessment of the body mass index and waist circumference were carried out using
      anthropometric measurements. The plasmatic and erythrocytary zinc were analyzed
      by method atomic absorption spectrophotometry (lambda = 213.9 nm). RESULTS: In
      the study, body mass index and waist circumference were higher in obese women
      than control group (p < 0.05). The mean plasmatic zinc was 72.2 +/- 9.0 MUg/dl in
      obese women and 73.4 +/- 8.5 MUg/dl in control group (p > 0.05). The mean
      erythrocytary zinc was 36.4 +/- 15.0 MUg/gHb and 45.4 +/- 14.3 MUg/gHb in the
      obese and controls, respectively (p < 0.05). Regression analysis showed that the
      body mass index (t =-2.85) and waist circumference (t = -2.37) have a negative
      relationship only with the erythrocytary zinc (R2 = 0.32, p < 0.05). CONCLUSIONS:
      The study shows that there are alterations in biochemical parameters of zinc in
      obese women, with low zinc concentrations in erythrocytes. Regression analysis
      demonstrates that the erythrocytary zinc is influenced by biomarkers of the
      metabolic syndrome, presenting an inverse relationship with the waist
      circumference and body mass index.

PMID- 21892589
TI  - [Ceruloplasmin and its clinical relevance as an indactor of cardiovascular risk
      factor in a school population of Granada].
AB  - Also known as ferroxidase ceruloplasmin, belongs to the family of inflammation
      sensitive proteins, and its main function to transport copper in the blood.
      Although, in addition to this transport function, at present, there are numerous
      studies that have attempted to use the determination of serum concentrations as a
      predictive indicator of cardiovascular risk in patients who are overweight or
      obese. The results of this study confirm the existence of a significant
      correlation between serum ceruloplasmin and nutritional status of the subjects,
      which means that for the population of students assessed, serum levels of this
      protein are an important predictor the risk of cardiovascular disease.

PMID- 21892590
TI  - Effects of fish oil and Tamoxifen on preneoplastic lesion development and
      biomarkers of oxidative stress in the early stages of N-methyl-N-nitrosourea
      induced rat mammary carcinogenesis.
AB  - Epidemiologic studies on the protective role of omega-3 fatty acids (n:3) on
      breast cancer prevention remain inconclusive but studies in preclinical models
      provide more positive outcome. However, the mechanisms accounting for the
      protective effect of n:3 are not defined. In the present study, conducted in the
      N-methyl-N-nitrosourea-induced rat mammary carcinogenesis model, we examined the
      effects of n:3 individually and in combination with the anti-estrogen Tamoxifen
      (Tam) on a comprehensive panel of systemic and preneoplastic mammary gland
      restricted biomarkers which may be critical in the progression to invasive
      cancer. We observed that fish oil (FO) rich diets significantly reduced Ki67
      expression in hyperplastic lesions, while cleaved caspase-3 expression was not
      affected. Dietary FO and/or Tam did not have major effects on systemic oxidative
      stress biomarkers, based on oxidative damage to DNA measured as 8-hydroxy-2
      deoxyguanosine (8-OH-dG) and lipid peroxidation assessed as thiobarbituric acid
      reactive substances (TBARS). Tissue levels of 8-isoprostane, on the other hand,
      were markedly reduced (p<0.0001) in FO-fed rats, possibly as a result of FO
      induced depletion of arachidonic acid in the mammary gland. These results suggest
      that the protective effect of n:3 in this experimental system is not mediated by
      changes in the levels of oxidative stress but may result from suppression of
      arachidonic acid-specific pathways.

PMID- 21892591
TI  - Establishment and evaluation of three necrotizing enterocolitis models in
      premature rats.
AB  - Necrotizing enterocolitis (NEC) is a gastrointestinal disease that usually
      affects premature infants and has high morbidity and mortality rates. Reliable
      animal models aid further study of the etiological factors, pathogenesis,
      prevention and treatment of NEC. The present study aimed to establish NEC models
      in premature rats using three common methods, and to determine the optimal model
      establishment method. The study consisted of six groups; in group A, rats were
      raised with simulated milk and subjected to inhalation of 100% nitrogen gas
      (hypoxia) for 90 sec, followed by exposure to cold ambient conditions (4C) for 10
      min twice daily for 3 days. In group B, rats were exposed to 100% nitrogen gas
      for 5 min and 100% oxygen for 5 min twice daily for 3 days. Group C rats were
      intraperitoneally administered 5 mg/kg lipopolysaccharide. Group D and E rats did
      not receive any intervention. Group F rats were intraperitoneally administered 1
      ml/kg physiological saline. Groups D-F served as the control groups corresponding
      to groups A-C, respectively. Following hematoxylin and eosin staining, intestinal
      tract, liver, lung and kidney tissues were observed under optical microscopy and
      were scored. Successful NEC induction was measured by a score of >=2. Rats from
      groups A-C exhibited reduced movement, abdominal distention, diarrhea, intestinal
      tract expansion, and congestion to varying degrees. The pathological scores of
      intestinal injury in groups A-F were 3.13+/-0.64, 1.40+/-0.52, 2.00+/-0.42,
      0.30+/-0.48, 0.30+/-0.48, and 0.40+/-0.52 points, respectively. Significant
      differences were found between the model groups and their corresponding control
      groups (p<0.01). Among the model groups, the histological score of group A was
      higher than that of groups B (p<0.01) and C (p<0.05). The morbidity rate of NEC
      in groups A-C was 75, 20 and 50%, respectively. There was no morbidity in groups
      D-F. Compared with groups A and B, injury to the liver, kidney and lung was more
      severe in group C. Similar symptoms were not observed in groups D-F. Compared
      with methods of simple hypoxia-reoxygenation or intraperitoneal administration of
      lipopolysaccharide, the combination of artificial feeding and hypoxia plus cold
      stimulation most resembles the pathological causes of neonatal NEC. This method
      resulted in high morbidity, reproducibility and specificity, and was therefore
      considered an ideal model for establishing NEC.

PMID- 21892592
TI  - Direct absorption of methyl mercury by lymph.
AB  - Methyl mercury is contained in fish and seafood products and is taken up into the
      body in food. While the central nervous system is known as a target organ, methyl
      mercury also induces autoimmunity and acts as a potent immunosuppressor. The aim
      of the present study is to know whether methyl mercury is directly absorbed by
      lymph. Conscious rats were infused with methyl mercury (4 mg/kg) via duodenal
      tubing as a single pulse infusion, followed by the continuous infusion of saline,
      and lymphatic fluids were continuously collected from the thoracic lymph duct
      every 30 min until 360 min after infusion. Mercury was detected immediately after
      infusion, and total mercury contents in lymph gradually increased until 90-120
      min, remained steady, and then gradually decreased until 360 min; however, the
      amount of mercury collected during 330-360 min was about twofold higher than
      during 0-30 min. The amount of cumulative mercury in lymph at 360 min was 1.4
      MUg. In contrast, blood mercury concentration was 2.4 MUg/ml 5 min after
      infusion, with the value at 360 min being 12.6 times higher than at 5 min. Plasma
      mercury concentration was 56 ng/ml at 5 min, with hundreds of nanograms per
      milliliter of mercury detected until 360 min. From the present study, it is
      concluded that some methyl mercury is directly absorbed by lymph and remains
      steady 6 h after infusion.

PMID- 21892593
TI  - Accumulation of calcium and phosphorus in the coronary arteries of Thai subjects.
AB  - To clarify the manner of accumulation of Ca and P in the coronary arteries, the
      authors divided the coronary arteries into many segments based on arterial
      ramification and investigated the element contents of the segments by direct
      chemical analysis. After ordinary dissection at Chiang Mai University was
      finished, the left coronary (LC) and the right coronary (RC) arteries were
      removed successively from the hearts of Thai subjects. The Thai subjects
      consisted of seven men and five women, ranging in age from 42 to 87 years
      (average age = 73.9 +/- 13.5 years). The LC and the RC arteries were divided into
      19 segments based on arterial ramification. After incineration with nitric acid
      and perchloric acid, element contents of the segments were analyzed by
      inductively coupled plasma-atomic emission spectrometry. In two cases, a
      significant content of Ca and P was contained only in the left anterior
      descending (LAD) artery (type I). In four cases, a significant content of Ca and
      P was contained in both the LAD and the RC arteries (type II). In five cases, a
      significant content of Ca and P was contained in all the LAD, the RC, and the
      circumflex (CF) arteries (type III). In the other one case, no significant
      content of Ca and P was contained in the coronary arteries. The manner of
      accumulation of Ca and P in the coronary arteries was classified into the three
      types, I, II, and III. Regarding the average content of elements in 12 cases, the
      average content of Ca was the highest in the segment of the LAD artery ramifying
      the first left diagonal artery and was higher in the proximal and distal adjacent
      segments of the LAD artery ramifying the first left diagonal artery, the proximal
      segment of the RC artery, and the proximal segment of the CF artery. To examine
      an effect of arterial ramification on accumulation of Ca and P, the differences
      in the Ca and P content between artery-ramifying and non-ramified proximal or
      distal segments of the coronary arteries were analyzed with Student's t test. It
      was found that there were no significant differences in the Ca and P content
      between the artery-ramifying and non-ramified proximal or distal segments of the
      coronary arteries.

PMID- 21892594
TI  - A randomized trial of cognitive behaviour therapy and cognitive therapy for
      children with posttraumatic stress disorder following single-incident trauma.
AB  - The present study compared the efficacy of trauma-focused cognitive behavior
      therapy (CBT) with trauma-focused cognitive therapy (without exposure; CT) for
      children and youth with posttraumatic stress disorder (PTSD). Children and youth
      who had experienced single-incident trauma (N = 33; 7-17 years old) were randomly
      assigned to receive 9 weeks of either CBT or CT which was administered
      individually to children and their parents. Intent-to-treat analyses demonstrated
      that both interventions significantly reduced severity of PTSD, depression, and
      general anxiety. At posttreatment 65% of CBT and 56% of the CT group no longer
      met criteria for PTSD. Treatment completers showed a better response (CBT: 91%;
      CT: 90%), and gains were maintained at 6-month follow-up. Maternal depressive
      symptoms and unhelpful trauma beliefs moderated children's outcome. It is
      concluded that PTSD secondary to single-incident trauma can be successfully
      treated with trauma-focused cognitive behavioural methods and the use of exposure
      is not a prerequisite for good outcome.

PMID- 21892595
TI  - Multi-wave prospective examination of the stress-reactivity extension of response
      styles theory of depression in high-risk children and early adolescents.
AB  - The current study tested the stress-reactivity extension of response styles
      theory of depression (Nolen-Hoeksema Journal of Abnormal Psychology 100:569-582,
      1991) in a sample of high-risk children and early adolescents from a
      vulnerability-stress perspective using a multi-wave longitudinal design. In
      addition, we examined whether obtained results varied as a function of either age
      or sex. During an initial assessment, 56 high-risk children (offspring of
      depressed parents; ages 7-14) completed measures assessing rumination and
      depressive symptoms. Children were subsequently given a handheld personal
      computer which signalled them to complete measures assessing depressive symptoms
      and negative events at six randomly selected times over an 8-week follow-up
      interval. In line with hypotheses, higher levels of rumination were associated
      with prospective elevations in depressive symptoms following the occurrence of
      negative events. Sex, but not age, moderated this association. Rumination was
      more strongly associated with elevations in depressive symptoms following the
      occurrence of negative events in girls than in boys.

PMID- 21892596
TI  - Medicare managed care and primary care quality: examining racial/ethnic effects
      across states.
AB  - The study assesses the role of Medicare Advantage (MA) plans in providing quality
      primary care in comparison to FFS Medicare in three states, New York, California,
      Florida, across three racial ethnic groups. The performance is measured in terms
      of providing better quality primary care, as defined by lowering the risks of
      preventable hospital admissions. Using 2004 hospital discharge data (HCUP-SID) of
      Agency for Healthcare Research and Quality for three states, a multivariate cross
      sectional design is used with individual admission as the unit of analysis. The
      study found that MA plans were associated with lower preventable hospitalizations
      relative to marker admissions. The benefit also spilled over to different racial
      and ethnic subgroups and in some states, e.g. CA and FL, MA enrollment was
      associated with significantly lower odds of minority admissions than of white
      admissions. These results may indicate a potentially favorable role of MA plans
      in attenuating racial/ethnic inequalities in primary care in some states.

PMID- 21892597
TI  - Development of fluorescent probes for the detection of fucosylated N-glycans
      using an Aspergillus oryzae lectin.
AB  - The alpha(1,6)-fucose attached to the core N-glycan (core fucose) of
      glycoproteins has been known to play essential roles in various
      pathophysiological events, including oncogenesis and metastasis. Aspergillus
      oryzae lectin (AOL) encoded by the fleA gene has been reported to bind to N
      glycans containing core fucose. The fleA gene encoding AOL was cloned into an
      Escherichia coli expression vector and then fused with genes of fluorescent
      proteins for production of fusion proteins. The resulting FleA-fluorescent fusion
      proteins were expressed well in E. coli and shown to detect glycoproteins
      containing N-glycans with core fucose by lectin blot assay. It was also shown to
      bind to the surface of cancer cells highly expressing the fucosyltransferase VIII
      for attachment of core fucose. Surprisingly, we found that FleA-fluorescent
      fusion proteins could be internalized into the intracellular compartment, early
      endosome, when applied to live cells. This internalization was shown to occur
      through a clathrin-mediated pathway by endocytosis inhibitor assay. Taken
      together, these results suggest that FleA-fluorescent fusion proteins can be
      employed as a valuable fluorescent probe for the detection of fucosylated glycans
      and/or a useful vehicle for delivery of substances to the inside of cells.

PMID- 21892598
TI  - Purification and characterization of heterologously expressed nitrilases from
      filamentous fungi.
AB  - Nitrilases from Aspergillus niger CBS 513.88, A. niger K10, Gibberella
      moniliformis, Neurospora crassa OR74A, and Penicillium marneffei ATCC 18224 were
      expressed in Escherichia coli BL21-Gold (DE3) after IPTG induction. N. crassa
      nitrilase exhibited the highest yield of 69,000 U L(-1) culture. Co-expression of
      chaperones (GroEL/ES in G. moniliformis and P. marneffei; GroEL/ES and trigger
      factor in N. crassa and A. niger CBS 513.88) enhanced the enzyme solubility.
      Specific activities of strains expressing the former two enzymes increased
      approximately fourfold upon co-expression of GroEL/ES. The enzyme from G.
      moniliformis (co-purified with GroEL) preferred benzonitrile as substrate (K(m)
      of 0.41 mM, V(max) of 9.7 MUmol min(-1) mg(-1) protein). The P. marneffei enzyme
      (unstable in its purified state) exhibited the highest V(max) of 7.3 MUmol min(
      1) mg(-1) protein in cell-free extract, but also a high K(m) of 15.4 mM, for 4
      cyanopyridine. The purified nitrilases from A. niger CBS 513.88 and N. crassa
      acted preferentially on phenylacetonitrile (K(m) of 3.4 and 2.0 mM, respectively;
      V(max) of 10.6 and 17.5 MUmol min(-1) mg(-1) protein, respectively), and
      hydrolyzed also (R,S)-mandelonitrile with higher K(m) values. Significant amounts
      of amides were only formed by the G. moniliformis nitrilase from
      phenylacetonitrile and 4-cyanopyridine.

PMID- 21892600
TI  - PET in T-Cell Lymphoma.
AB  - Most non-Hodgkin lymphomas (NHL) are of B-cell origin; only about 10% are T-cell
      or NK-cell lymphomas. The clinical features of T/NK-cell lymphomas differ from
      those of B-cell lymphomas: advanced stage and extranodal disease are more common
      and the prognosis is worse. Several studies have confirmed that 2-[fluorine
      18]fluoro-2-deoxy-D-glucose (18FDG) uptake varies among different subtypes of
      lymphoma, a disparity that can be explained by the differences in histology,
      proliferation of tumor cells, and the ratio of viable tumor and reactive cells in
      the environment. These observations are based on investigation of B-cell
      lymphomas. Positron emission tomography (PET)/computed tomography (CT) was found
      to be useful both at staging and at measuring the therapeutic outcome after two
      to three cycles of chemotherapy (interim PET/CT). Several meta-analyses have
      confirmed the role of PET in evaluating the viability of the residual tumor mass
      after treatment. 18FDG-PET has been proved to have an excellent negative
      predictive value. Conversely, only a few studies have investigated the role of
      FDG-PET in T/NK-cell lymphomas. This paper summarizes the current information
      regarding the potential use of PET/CT in patients with T-cell lymphoma.

PMID- 21892599
TI  - A type of voltage-dependent Ca2+ channel on Vicia faba guard cell plasma membrane
      outwardly permeates K+.
AB  - The fine regulation of stomatal aperture is important for both plant
      photosynthesis and transpiration, while stomatal closing is an essential plant
      response to biotic and abiotic stresses such as drought, salinity, wounding, and
      pathogens. Quick stomatal closing is primarily due to rapid solute loss.
      Cytosolic free calcium ([Ca(2+)](cyt)) is a ubiquitous second messenger, and its
      elevation or oscillation plays important roles in stomatal movements, which can
      be triggered by the opening of Ca(2+)-permeable channels on the plasma membrane.
      For Ca(2+)-permeable channel recordings, Ba(2+) is preferred as a charge-carrying
      ion because it has higher permeability to Ca(2+) channels and blocks K(+) channel
      activities to facilitate current recordings; however, it prevents visualization
      of Ca(2+) channels' K(+) permeability. Here, we employed Ca(2+) instead of Ba(2+)
      in recording Ca(2+)-permeable channels on Vicia faba guard cell plasma membrane
      to mimic physiological solute conditions inside guard cells more accurately.
      Inward Ca(2+) currents could be recorded at the single-channel level, and these
      currents could be inhibited by micromolar Gd(3+), but their reversal potential is
      far away from the theoretical equilibrium potential for Ca(2+). Further
      experiments showed that the discrepancy of the reversal potential of the recorded
      Ca(2+) currents is influenced by cytosolic K(+). This suggests that voltage
      dependent Ca(2+) channels also mediate K(+) efflux at depolarization voltages. In
      addition, a new kind of high-conductance channels with fivefold to normal Ca(2+)
      channel and 18-fold to normal outward K(+) conductance was found. Our data
      presented here suggest that plants have their own saving strategies in their
      rapid response to stress stimuli, and multiple kinds of hyperpolarization
      activated Ca(2+)-permeable channels coexist on plasma membranes.

PMID- 21892601
TI  - The construction of an oxalate-degrading intestinal stem cell population in mice:
      a potential new treatment option for patients with calcium oxalate calculus.
AB  - About 80% of all urological stones are calcium oxalate, mainly caused by
      idiopathic hyperoxaluria (IH). The increased absorption of oxalate from the
      intestine is the major factor underlying IH. The continuous self-renewal of the
      intestinal epithelium is due to the vigorous proliferation and differentiation of
      intestinal stem cells. If the intestinal stem cell population can acquire the
      ability to metabolize calcium oxalate by means of oxc and frc transgenes, this
      will prove a promising new therapy option for IH. In our research, the oxalate
      degrading genes of Oxalobacter formigenes (Oxf)-the frc gene and oxc gene-were
      cloned and transfected into a cultured mouse-derived intestinal SC population to
      give the latter an oxalate-degrading function. Oxf was isolated and cultivated
      and the oxalate-degrading genes-frc and oxc-were cloned. The dicistronic
      eukaryotic expression vector pIRES-oxc-frc was constructed and transferred into
      the mouse stem cell population. After selection with G418, the expression of the
      genes was identified. The oxalate-degrading function of transfected cells was
      determined by transfection into the intestinal stem cell population of the mouse.
      The change in oxalate concentration was determined with an ion chromatograph. The
      recombinant plasmid containing oxc and frc genes was transfected into the stem
      cell population of the mouse and the expression of the genes found normal. The
      cell population had acquired an oxalate-degrading function. The oxc and frc genes
      could be transfected into the intestinal stem cell population of the mouse and
      the cells acquired an oxalate-degrading function.

PMID- 21892602
TI  - Two- and three-dimensional culture of keratinocyte stem and precursor cells
      derived from primary murine epidermal cultures.
AB  - In the skin, multipotent keratinocyte stem cells (KSC) are localised in the hair
      follicle bulge region. Although, KSC can be cultivated and grown in two
      dimensional (2D) culture they rapidly lose stem cell markers when isolated from
      their niche. Currently, there is no KSC culture method available which
      recapitulates an environment similar to the KSC niche in the hair follicle. Here
      we describe the successful establishment of an in vitro 3D stem cell culture
      model developed from clonally growing keratinocyte lines derived from neonatal
      mice using culture conditions previously established for human keratinocytes.
      After 20 passages, keratinocyte lines showed a stable ratio of holoclones (stem
      cells), meroclones (stem and precursor cells) and paraclones (differentiating
      cells), with approximately 29% holoclones, 54% meroclones and 17% paraclones, and
      were thus termed keratinocyte stem and precursor cell (KSPC) cultures. In high
      calcium medium, KSPC cultures grown at the air-liquid interphase differentiated
      and formed epidermal equivalents. Notably, and in contrast to primary
      keratinocytes, keratinocytes from KSPC cultures were able to aggregate and form
      spherical clusters in hanging drops, a characteristic hallmark shared with other
      stem cell types. Similar to the in vivo situation in the hair follicle bulge,
      KSPC aggregates also showed low proliferation, down-regulation of keratin 6,
      absence of keratin 1, and expression of the KSC markers keratin 15, Sox9, NFATc1
      and Zfp145. KSPC aggregates therefore provide an optimal in vitro 3D environment
      for the further characterisation and study of normal and genetically modified
      KSPC.

PMID- 21892604
TI  - Navigated laparoscopic ultrasound in abdominal soft tissue surgery: technological
      overview and perspectives.
AB  - PURPOSE: Two-dimensinal laparoscopic ultrasound (LUS) is commonly used for many
      laparoscopic procedures, but 3D LUS and navigation technology are not
      conventional tools in the clinic. Navigated LUS can help the user understand and
      interpret the ultrasound images in relation to the laparoscopic view and
      preoperative images. When combined with information from MRI or CT, navigated LUS
      has the potential to provide information about anatomic shifts during the
      procedure. In this paper, we present an overview of the ongoing technological
      research and development related to LUS combined with navigation technology, The
      purpose of this overview is threefold: (1) an introduction for those new to the
      field of navigated LUS; (2) an overview for those working in the field and; and
      (3) as a reference for those searching for literature on technological
      developments related to navigation in ultrasound-guided laparoscopic surgery.
      METHODS: Databases were searched to identify relevant publications from the last
      10 years. RESULTS: We were able to identify 18 key papers in the area of
      navigated LUS for the abdomen, originating from about 10-11 groups. We present
      the literature overview, including descriptions of our own experience in the
      field, and a discussion of the important clinical and technological aspects
      related to navigated LUS. CONCLUSIONS: LUS integrated with miniaturized tracking
      technology is likely to play an important role in guiding future laparoscopic
      surgery.

PMID- 21892605
TI  - The characterization of functional disturbances in Chinese patients with Bietti's
      crystalline dystrophy at different fundus stages.
AB  - PURPOSE: The aim of this study was to characterize the functional and clinical
      disturbances and screen the optimal functional tests in assessing Bietti's
      crystalline dystrophy (BCD) patients by a cross-sectional method. METHODS: The
      clinical characteristics of BCD were studied in 15 Chinese patients using
      fundoscopy, fundus fluorescein angiography (FFA), and autofluorescence (AF). The
      functional features were evaluated by full-field electroretinography (fERG), 85o
      and 30o perimetry, multifocal ERG (mERG), and chromatic pupillometry. RESULTS:
      The 15 patients were separated into three clinical stages according to their
      fundus features. fERG- and mERG- showed reduced reponses in the early stages.
      Substages could be further defined according to the fERG results in the
      intermediate stages. Reduced pupillary light reflex (PLR) activities with blue
      and white-light stumili existed in all patients. The most reduced PLR activities
      were elicited in the advanced stage of patients who had other nonresponsive
      functional tests. CONCLUSIONS: This study identified the most sensitive
      functional methods for assessing BCD patients, and the significance of PLR in the
      advanced stages. In addition, the defined-substages can help us understand the
      disease more clearly.

PMID- 21892606
TI  - Sperm carriers in Silurian sea scorpions.
AB  - Invasion of the land by arachnids required adaptations of numerous organs, such
      as gills evolving into lungs, as well as mechanisms facilitating sperm transfer
      in a terrestrial environment. Many modern arachnids use spermatophores for this
      purpose, i.e. sperm transmitters detached from the body. Exceptionally preserved
      Silurian (423 Ma) fossils of Eurypterus tetragonophthalmus Fischer, 1839
      (Chelicerata: Eurypterida) preserve so-called 'horn organs' which we here
      demonstrate as being equivalent to the spermatophore-producing parts of the
      genital tract in certain modern arachnids. This clarifies a long-running debate
      about sexing eurypterids based on the shape of the median abdominal (or genital)
      appendage. To our knowledge this is also the oldest direct evidence for
      spermatophore-mediated sperm transfer in the fossil record and suggests that
      eurypterids had evolved mating techniques using spermatophores as early as the
      Silurian, a valuable prerequisite for life on land. Spermatophores are absent in
      sea spiders (Pycnogonida) and horseshoe crabs (Xiphosura); thus the shared
      presence of sclerotized sperm-transfer devices in eurypterids and arachnids is a
      novel character, newly elucidated here, which offers explicit support for
      (Eurypterida + Arachnida). For this clade the name Sclerophorata n. nov. is
      proposed. Arachnida can be further defined by fusion of the originally paired
      genital opening.

PMID- 21892603
TI  - Immunosuppressive properties of mesenchymal stem cells.
AB  - Mesenchymal stem cells (MSC) can be isolated from different adult tissues
      including bone marrow, adipose tissue, cord blood and placenta. MSCs modulate the
      immune function of the major immune cell populations involved in alloantigen
      recognition and elimination, including antigen presenting cells, T cells, B cells
      and natural killer cells. Many clinical trials are currently underway that employ
      MSCs to treat human immunological diseases. However, the molecular mechanism that
      mediates the immunosuppressive effect of MSCs is still unclear and the safety of
      using MSC in patient needs further confirmation. Here, we review the cytokines
      that activate MSCs and the soluble factors produced by MSCs, which allow them to
      exert their immunosuppressive effects. We review the mechanism responsible, at
      least in part, for the immune suppressive effects of MSCs and highlight areas of
      research required for a better understanding of MSC immune modulation.

PMID- 21892608
TI  - Extraperitoneal vs. intraperitoneal route for permanent colostomy: a meta
      analysis of 1,071 patients.
AB  - BACKGROUND: Parastomal hernia is a common complication after colostomy
      construction. Whether an extraperitoneal route for colostomy creation can reduce
      the risk of parastomal hernia remains controversial. OBJECTIVE: A meta-analysis
      was performed to evaluate the value of extraperitoneal route in the prevention of
      parastomal hernia and other postoperative complications related to colostomy.
      DATA SOURCES: A literature search of Medline, Embase, Ovid, and Cochrane
      databases from the years 1966 to 2010 was performed. STUDY SELECTION: Studies
      comparing extraperitoneal colostomy with intraperitoneal colostomy were
      identified. INTERVENTION: Extraperitoneal colostomy was performed to prevent
      colostomy-related complications. MAIN OUTCOME MEASURES: Data on the following
      outcomes were sought: incidence of postoperative colostomy complications
      including parastomal hernia, prolapse, and bowel obstruction. RESULTS: Seven
      retrospective studies with a combined total of 1,071 patients (250
      extraperitoneal colostomy and 821 intraperitoneal colostomy) were identified.
      There was a significantly lower rate of parastomal hernia (odds ratio, 0.41; 95%
      confidence interval, 0.23-0.73, p = 0.002) in the extraperitoneal colostomy
      group. However, the occurrences of bowel obstruction and prolapse were not
      significantly different between the two groups. LIMITATIONS: A limitation of the
      study lies on the meta-analysis of observational studies. CONCLUSION:
      Extraperitoneal colostomy is associated with a lower rate of postoperative
      parastomal hernia as compared to intraperitoneal colostomy. Prospective
      randomized controlled trial is warranted to further determine the role of
      extraperitoneal route in the prevention of parastomal hernia.

PMID- 21892607
TI  - Downregulation of Notch-1/Jagged-2 in human colon tissues from Hirschsprung
      disease patients.
AB  - PURPOSE: Recent studies have shown that the Notch pathways play important roles
      in the differentiation and development of neurons. Hirschsprung disease (HSCR) is
      characterized by the absence of intramural ganglion cells in the nerve plexuses
      of the distal gut. However, putative Notch function in enteric nervous system
      (ENS) development and the etiology of HSCR is unknown. MATERIALS AND METHODS: The
      aganglionosis segments of 30 HSCR patients were introduced to investigate the
      expression pattern of Notch-1 and Jagged-2 using immunohistochemical staining,
      reverse transcriptase polymerase chain reaction (RT-PCR), and Western blot
      analysis. RESULTS: Intensive Notch-1 and Jagged-2 staining was detected in the
      submucosal and the myenteric plexuses in normal or oligoganglionosis segments.
      Aganglionosis segments from HSCR patients contained no plexuses and thus not
      labeled with Notch-1 and Jagged-2. Western blot analysis revealed reduced Notch-1
      and Jagged-2 protein levels, and RT-PCR revealed reduced Notch-1 and Jagged-2
      mRNA in the aganglionosis segments of HSCR patients. CONCLUSIONS: This study is
      the first illustration of Notch-1 and Jagged-2 expression in human tissues from
      non-cancerous disease and sets up the base for further investigations of Notch
      function in ENS development and intestinal motility.

PMID- 21892609
TI  - Benzyl isothiocyanate inhibits basal and hepatocyte growth factor-stimulated
      migration of breast cancer cells.
AB  - Benzyl isothiocyanate (BITC), which is found in cruciferous vegetables, has been
      shown to have anti-carcinogenic properties. Hepatocyte growth factor (HGF) has
      the ability to stimulate dissociation, migration, and invasion in various tumor
      cells, and abnormally increased expressions of HGF and its transmembrane tyrosine
      kinase receptor, c-Met, have previously been detected in human breast cancer, and
      are associated with high tumor grade and poor prognosis. In this study, in order
      to assess the mechanisms relevant to the BITC-induced regulation of breast cancer
      cell migration and invasion, MDA-MB-231 human breast cancer cells and 4T1 murine
      mammary carcinoma cells were cultured in the presence of 0-4 MUmol/l BITC with or
      without 10 MUg/l of HGF. BITC inhibited both the basal and HGF-induced migration
      of MDA-MB-231 and 4T1 cells in a dose-dependent manner. In MDA-MB-231 cells, BITC
      reduced both basal and HGF-induced secretion and activity of urokinase-type
      plasminogen activator (uPA). In addition, BITC increased the protein levels of
      plasminogen activator inhibitor-1. HGF stimulated c-Met and Akt phosphorylation,
      but did not affect the phosphorylation of extracellular signal-regulated kinase
      1/2 or stress-activated protein/c-jun N-terminal kinase. BITC suppressed NF
      kappaB activity and reduced the HGF-induced phosphorylation of c-Met and Akt in a
      dose-dependent manner. LY294002, a specific Akt inhibitor, reduced both basal and
      HGF-induced uPA secretion and migration of MDA-MB-231 cells. In this study, we
      demonstrated that BITC profoundly inhibits the migration and invasion of MDA-MB
      231 cells, which is associated with reduced uPA activity, and also that these
      phenomena are accompanied by the suppression of Akt signaling.

PMID- 21892610
TI  - Computed tomographic angiography identification of intramural segments in
      anomalous coronary arteries with interarterial course.
AB  - Certain coronary anomalies are associated with high risk features. We sought to
      determine the diagnostic accuracy of coronary computed tomographic angiography
      (CTA) in determining high-risk features, particularly intramural segments.
      Anomalous coronary arteries can be associated with adverse clinical events.
      Anomalous coronaries that course between the great vessels (interarterial) have
      been associated with sudden death. High-risk features of interarterial vessels
      described in the literature include; a slit-like orifice, acute angle of origin,
      and intramural segments (within the wall of the aorta). Although computed
      tomography (CT) findings of acute angle and slit like orifice have been described
      previously no prior evaluations regarding CT identification of an intramural
      segment have been reported. An intramural segment has distinct surgical
      management implications. All interarterial anomalous coronary arteries do not
      have an intramural segment. Since October 2004, 15 patients were diagnosed by CTA
      as having an anomalous coronary artery with an interarterial course, which were
      then confirmed by intraoperative examination of their coronary origins and course
      during aortic root/coronary artery surgery. The CTA images were retrospectively
      analyzed for the presence of high-risk features by a radiologist blinded to the
      surgical findings. Comparison of these findings was made to the findings at
      surgery. The anomalous coronary was the right coronary artery in 10 patients and
      the left coronary artery in 5. Eleven patients had an intramural segment
      identified at surgery. Pre-operative coronary CTA showed that all patients with
      an intramural course of the anomalous artery, had slit-like orifice, an acute
      angle of origin (mean 18.4 +/- 3.4 degrees ), and an elliptical shaped cross
      section throughout the intramural segment of the anomalous vessel. The average
      vessel height/width ratio for anomalous coronary vessels without an intramural
      segment was 1.03; compared to a ratio of 2.19 for anomalous vessels with an
      intramural segment (P = 0.003). Coronary CTA can identify an intramural segment
      of an anomalous interarterial coronary artery by its elliptical shape.
      Identifying an intramural segment has important clinical and surgical
      implications.

PMID- 21892611
TI  - Salivary enzymes and exhaled air affect Streptococcus salivarius growth and
      physiological state in complemented artificial saliva.
AB  - To better understand the phenomena governing the establishment of the oral
      bacterium Streptococcus salivarius in the mouth, the effect of some environmental
      factors has been studied in complemented artificial saliva, under oral pH and
      temperature conditions. Three salivary enzymes at physiological concentrations
      were tested: peroxidase, lysozyme and amylase, as well as injection of exhaled
      air. Injection of air containing 5% CO2 and 16% O2 induced a deleterious effect
      on S. salivarius K12, mainly by increasing redox potential. Addition of lysozyme
      slightly affected the physiological state of S. salivarius by altering membrane
      integrity. In contrast, peroxidase was not detrimental as it made it possible to
      decrease the redox potential. The addition of amylase reduced the specific growth
      rate of S. salivarius by formation of a complex with amylase and mucins, but led
      to high final biomass, as a result of enzymatic degradation of some nutrients.
      Finally, this work demonstrated that salivary enzymes had a slight impact on S.
      salivarius behaviour. It can thus be concluded that this bacterium was well
      adapted to in-mouth conditions, as it was able to resist certain salivary
      enzymes, even if tolerance to expired air was affected, as a result of an
      increased redox potential.

PMID- 21892612
TI  - Resveratrol attenuates apoptosis of pulmonary microvascular endothelial cells
      induced by high shear stress and proinflammatory factors.
AB  - Endothelial injury usually underlies the initial pathologic step of
      cardiovascular diseases. Primary endothelial cell (EC) apoptosis and secondary
      hyperproliferation both contribute to the development of atherosclerosis and
      luminal occlusion. In order to investigate the effects of resveratrol (RSV) on EC
      apoptosis, we applied high shear stress (HSS) with proinflammatory factors [tumor
      necrosis factor alpha (TNF-alpha) plus cycloheximide] to human pulmonary
      microvascular ECs (PMVECs) through an artificial capillary system. Intracellular
      reactive oxygen species (ROS) was measured by spectrofluorometry using
      dihydrorhodamine 123 fluorescent probe. Apoptosis and proliferation was
      determined by flow cytometric analysis. Protein expression was examined by
      Western blot. HSS plus inflammation significantly raised the ROS and the
      apoptosis level of PMVECs, which could be diminished by RSV pretreatment. In a 7
      days incubation assay, RSV effectively inhibited the initial increase in
      apoptosis and thereby prevented subsequent PMVEC hyperproliferation induced by
      HSS plus inflammation. Mercaptosuccinate, a glutathione peroxidase (GPx-1)
      inhibitor or nicotinamide, a silent information regulator 2/sirtuin 1 (SIRT1)
      inhibitor could attenuate the antiapoptotic action of RSV on PMVECs; and RSV
      treatment upregulated GPx-1 and SIRT1 expression in PMVECs. In conclusion, RSV,
      probably by activating SIRT1 signaling pathway, inhibits the oxidative-stress
      dependent phenotypical shift of ECs induced by HSS and proinflammatory factors in
      vitro.

PMID- 21892613
TI  - Saccharothrix yanglingensis sp. nov., an antagonistic endophytic actinomycete
      isolated from cucumber plant.
AB  - An endophytic actinomycete strain, designated Hhs.015(T), was isolated from roots
      of cucumber seedlings. The endophytic isolate was identified by means of a
      polyphasic taxonomic approach. On the basis of 16S rRNA gene sequence
      similarities, strain Hhs.015(T) was closely related to members of the genus
      Saccharothrix. DNA-DNA hybridization with the four closest relatives,
      Saccharothrix longispora NRRL B-16116(T), Saccharothrix xinjiangensis NRRL B
      24321(T), Saccharothrix autraliensis CGMCC 4.1355(T) and Saccharothrix
      espanaensis CGMCC 4.1714(T), gave similarity values of 33.8, 28.2, 44.1 and
      29.5%, respectively, which indicated that strain Hhs.015(T) represents a novel
      species of the genus Saccharothrix. This is consistent with the morphological,
      physiological and chemotaxonomic data. As a whole, these results suggest that
      strain Hhs.015(T) represents a novel Saccharothrix species. The name
      Saccharothrix yanglingensis sp. nov. is proposed, with the type strain Hhs.015(T)
      (=CGMCC 4.5627(T) = KCTC 19722(T)).

PMID- 21892614
TI  - Molecular characterization of a rice metal tolerance protein, OsMTP1.
AB  - Rice (Oryza sativa L. 'Nipponbare') cDNA subtractive suppression hybridization
      (SSH) libraries constructed using cadmium (Cd)-treated seedling roots were
      screened to isolate Cd-responsive genes. A cDNA clone, encoding the rice homolog
      of Metal Tolerance Protein (OsMTP1), was induced by Cd treatment. Plant MTPs
      belong to cation diffusion facilitator (CDF) protein family, which are widespread
      in bacteria, fungi, plants, and animals. OsMTP1 heterologous expression in yeast
      mutants showed that OsMTP1 was able to complement the mutant strains'
      hypersensitivity to Ni, Cd, and Zn, but not other metals including Co and Mn.
      OsMTP1 expression increased tolerance to Zn, Cd, and Ni in wild-type yeast BY4741
      during the exponential growth phase. OsMTP1 fused to green fluorescent protein
      was localized in onion epidermal cell plasma membranes, consistent with an OsMTP1
      function in heavy metal transporting. OsMTP1 dsRNAi mediated by transgenic assay
      in rice seedlings resulted in heavy metal sensitivity and changed the heavy metal
      accumulation in different organs of mature rice under low-concentration heavy
      metal stress. Taken together, our results show that OsMTP1 is a bivalent cation
      transporter localized in the cell membrane, which is necessary for efficient
      translocation of Zn, Cd and other heavy metals, and maintain ion homeostasis in
      plant.

PMID- 21892615
TI  - Assessment of radiological hazard of NORM in Margalla Hills limestone, Pakistan.
AB  - Studies on naturally occurring radioactive material (NORM) in the limestone from
      the Margalla Hills have been carried out by measuring gamma activity and to
      access its radiological implications if any. For data acquisition, a High-Purity
      Germanium detector was employed. The activity concentrations of (226)Ra, (232)Th,
      and (40)K were found to be 14.32 +/- 0.24, 2.05 +/- 0.04, and 13.80 +/- 0.20 Bq
      kg(-1), respectively. These values are relatively lower as compared to that in
      the limestone of other countries and much lower than the values reported for the
      natural building stones. The average specific activities due to (226)Ra were
      found to be higher when compared with (40)K and (232)Th. Indices of radium
      equivalent activity (Ra(eq)), internal hazard (H(in)), indoor absorbed gamma dose
      rate (D(R,)), and corresponding annual effective dose (E(eff)) were also
      determined for the limestone-made rooms. All of these indices were found to be in
      the lower ranges. The Margalla Hills limestone does not pose any excessive
      radiological health hazard as a building material and in industrial uses for a
      common man.

PMID- 21892616
TI  - Isolation of phlorotannins from Eisenia bicyclis and their hepatoprotective
      effect against oxidative stress induced by tert-butyl hyperoxide.
AB  - Eisenia bicyclis (Kjellman) Setchell is a common brown alga that inhabits the
      middle Pacific coast around Korea and Japan. In this study, the ethanol extract
      and its serial solvent fractions were prepared from fresh E. bicyclis, and their
      hepatoprotective effects were investigated against hepatotoxicity in tert-butyl
      hyperoxide(t-BHP)-injured HepG2 cells. When these samples were used at a dose of
      10-40 MUg/mL-1, they significantly protected the t-BHP-induced cell death in
      HepG2 cells. Among fractions, ethyl acetate fraction (EF) and n-butanol extract
      (BF) exhibited potent hepatoprotective activities (62.60% for EF and 64.86% for
      BF) in t-BHP-injured HepG2 cells at a concentration of 10 MUg/mL-1. To find the
      potential factors for this activity, the samples were characterized on total
      phenolics, chlorophylls, carotenoids, and radical scavenging activity. Among
      them, EF showed the highest content of total phenolics and the strongest
      antioxidant activity both in on- and offline assays. Five phlorotannin compounds,
      oligomers of phloroglucinol, were isolated chromatographically from this fraction
      and structurally identified by (1)H-NMR and liquid chromatography-electrospray
      ionization-mass spectrometry analyses as eckol(1), 6,6'-bieckol(2), 8,8'
      bieckol(3), dieckol(4), and phlorofucofuroeckol A(5). Compound 5 among five
      purified compounds showed the strongest protective activity (45.54%) at a
      concentration of 10 MUM. At the high dose (40 MUM), the protective activities of
      three compounds (compound 2, 4, and 5) were higher than that of quercetin treated
      with 10 MUM concentration. Therefore, we can speculate that they can be developed
      as potential candidates for natural hepatoprotective agents.

PMID- 21892617
TI  - Resection of liver metastases is beneficial in patients with gastric cancer:
      report on 15 cases and review of literature.
AB  - BACKGROUND: Although up to 9% of patients with gastric cancer develop liver
      metastases, liver resection is rarely performed because of co-existing non
      curative factors. Furthermore, the benefit of liver resection is still
      controversially discussed. Our goal was to investigate the outcome of patients
      who underwent liver resection or radiofrequency ablation (RFA) for hepatic
      metastasized gastric cancer. METHODS: Retrospectively collected data from a
      prospectively maintained database were analyzed from 15 patients who underwent
      liver resection or RFA for liver metastases from gastric cancer. RESULTS: Overall
      5-year survival and median survival were 27% and 48 months for resected/RFA
      patients. The peri-operative complication rate was low. One patient has been
      tumor-free for 90 months now. CONCLUSIONS: Liver resection in patients with
      hepatic metastasized gastric cancer is beneficial and safe if an R0 situation can
      be achieved. RFA might be a useful alternative in those patients where surgery is
      not feasible.

PMID- 21892618
TI  - HRD1 levels increased by zonisamide prevented cell death and caspase-3 activation
      caused by endoplasmic reticulum stress in SH-SY5Y cells.
AB  - Zonisamide, which is commonly prescribed at high doses (200-400 mg/day) for the
      treatment of partial seizures, has recently been used at a low dose (25 mg/day)
      for improving parkinsonian syndrome. However, the molecular mechanisms that
      underlie the antiparkinsonian effects of zonisamide have not been clarified. Here
      we show that low micromolar concentrations of zonisamide prevented cleavage of
      caspase-3 and cell death in human dopaminergic SH-SY5Y neuroblastoma cells that
      were subjected to endoplasmic reticulum stress induced by tunicamycin or 6
      hydroxydopamine. Hypodense zonisamide increased the expression levels of SEL1L,
      which is known to stabilize the ubiquitin ligase HRD1. Indeed, upregulation of
      HRD1 protein was observed. Thus, the results of this study strongly suggest that
      low concentrations of zonisamide inhibit neuronal cell death by increasing HRD1
      protein levels in patients with Parkinson's disease. Consequently, in addition to
      the treatment of Parkinson's disease, the therapeutic potential of zonisamide
      should be considered for the treatment of several neurodegenerative disorders
      with pathophysiological mechanisms involving endoplasmic reticulum stress.

PMID- 21892619
TI  - Parkinsonism and frontotemporal dementia: the clinical overlap.
AB  - Frontotemporal dementia is commonly associated with parkinsonism in several
      sporadic (i.e., progressive supranuclear palsy, corticobasal degeneration) and
      familial neurodegenerative disorders (i.e., frontotemporal dementia associated
      with parkinsonism and MAPT or progranulin mutations in chromosome 17). The
      clinical diagnosis of these disorders may be challenging in view of overlapping
      clinical features, particularly in speech, language, and behavior. The motor and
      cognitive phenotypes can be viewed within a spectrum of clinical, pathologic, and
      genetic disorders with no discrete clinicopathologic correlations but rather
      lying within a dementia-parkinsonism continuum. Neuroimaging and cerebrospinal
      fluid analysis can be helpful, but the poor specificity of clinical and imaging
      features has enormously challenged the development of biological markers that
      could differentiate these disorders premortem. This gap is critical to bridge in
      order to allow testing of novel biological therapies that may slow the
      progression of these proteinopathies.

PMID- 21892620
TI  - The multiple faces of valosin-containing protein-associated diseases: inclusion
      body myopathy with Paget's disease of bone, frontotemporal dementia, and
      amyotrophic lateral sclerosis.
AB  - Inclusion body myopathy associated with Paget's disease of bone and
      frontotemporal dementia (IBMPFD) is a progressive, fatal genetic disorder with
      variable penetrance, predominantly affecting three main tissue types: muscle
      (IBM), bone (PDB), and brain (FTD). IBMPFD is caused by mutations in the
      ubiquitously expressed valosin-containing protein (VCP) gene, a member of the AAA
      ATPase superfamily. The majority of individuals who develop IBM have progressive
      proximal muscle weakness. Muscle biopsies reveal rimmed vacuoles and inclusions
      that are ubiquitin- and TAR DNA binding protein-43 (TDP-43)-positive using
      immunohistochemistry. PDB, seen in half the individuals, is caused by overactive
      osteoclasts and is associated clinically with pain, elevated serum alkaline
      phosphatase, and X-ray findings of coarse trabeculation and sclerotic lesions.
      FTD diagnosed at a mean age of 55 years in a third of individuals is
      characterized clinically by comprehension deficits, dysnomia, dyscalculia, and
      social unawareness. Ubiquitin- and TDP-43-positive neuronal inclusions are also
      found in the brain. Genotype-phenotype correlations are difficult with marked
      intra-familial and inter-familial variations being seen. Varied phenotypes within
      families include frontotemporal dementia, amyotrophic lateral sclerosis,
      Parkinsonism, myotonia, cataracts, and anal incompetence, among others. Cellular
      and animal models indicate pathogenetic disturbances in IBMPFD tissues including
      altered protein degradation, autophagy pathway alterations, apoptosis, and
      mitochondrial dysfunction. Currently, mouse and drosophila models carrying VCP
      mutations provide insights into the human IBMPFD pathology and are useful as
      tools for preclinical studies and testing of therapeutic strategies. In this
      review, we will explore the pathogenesis and clinical phenotype of IBMPFD caused
      by VCP mutations.

PMID- 21892622
TI  - Quantification of receptor-ligand binding with [18F]fluciclatide in metastatic
      breast cancer patients.
AB  - PURPOSE: The purpose of the study was to estimate the receptor-ligand binding of
      an arginine-glycine-aspartic acid (RGD) peptide in somatic tumours. To this aim,
      we employed dynamic positron emission tomography (PET) data obtained from breast
      cancer patients with metastases, studied with the alpha(v)beta(3/5) integrin
      receptor radioligand [(18)F]fluciclatide. METHODS: First, compartmental modelling
      and spectral analysis with arterial input function were performed at the region
      of interest (ROI) level in healthy lung and liver, and in lung and liver
      metastases; compartmental modelling was also carried out at the pixel level. The
      selection of the most appropriate indexes for tumour/healthy tissue
      differentiation and for estimation of specific binding was then assessed.
      RESULTS: The two-tissue reversible model emerged as the best according to the
      Akaike Information Criterion. Spectral analysis confirmed the reversibility of
      tracer kinetics. Values of kinetic parameters, estimated as mean from parametric
      maps, correlated well with those computed from ROI analysis. The volume of
      distribution V(T) was on average higher in lung metastases than in the healthy
      lung, but lower in liver metastases than in the healthy liver. In agreement with
      the expected higher alpha(v)beta(3/5) expression in pathology, k(3) and k(3)/k(4)
      were both remarkably higher in metastases, which makes them more suitable than
      V(T) for tumour/healthy tissue differentiation. The ratio k(3)/k(4), in
      particular, appeared a reasonable measure of specific binding. CONCLUSION:
      Besides establishing the best quantitative approaches for the analysis of
      [(18)F]fluciclatide data, this study indicated that the k(3)/k(4) ratio is a
      reasonable measure of specific binding, suggesting that this index can be used to
      estimate alpha(v)beta(3/5) receptor expression in oncology, although further
      studies are necessary to validate this hypothesis.

PMID- 21892623
TI  - Peptide receptor radionuclide therapy with 177Lu-DOTATATE: the IEO phase I-II
      study.
AB  - PURPOSE: Peptide receptor radionuclide therapy (PRRT) is used in tumours
      expressing type 2 somatostatin receptors (sst(2)), mainly neuroendocrine. The aim
      of this prospective phase I-II study was to evaluate the toxicity and efficacy of
      (177)Lu-DOTATATE in multiple cycles. METHODS: Fifty-one consecutive patients with
      unresectable/metastatic sst(2)-positive tumours, divided into two groups,
      received escalating activities (3.7-5.18 GBq/cycle, group 1; 5.18-7.4 GBq/cycle,
      group 2) of (177)Lu-DOTATATE. Cumulative activities ranged from 3.7 to 29.2 GBq
      (median 26.4 GBq in median 6 cycles, group 1, 21 patients) and 5.55 to 28.9 GBq
      (median 25.2 GBq in 4 cycles, group 2, 30 patients), based on dosimetry. RESULTS:
      No major acute or delayed renal or haematological toxicity occurred (one grade 3
      leukopenia and thrombocytopenia). Cumulative renal absorbed doses were 8-37 Gy (9
      41 Gy bioeffective doses). A median decrease of creatinine clearance of 21.7% 6
      months after PRRT, 23.9% after 1 year and 27.6% after 2 years was observed.
      Higher losses (>20%) occurred in patients with risk factors for renal toxicity,
      particularly hypertension and diabetes. Cumulative bone marrow doses were <1.5
      Gy. Blood elements showed a progressive mild drop during cycles and recovered
      during follow-up (median 30 months). Thirty-nine patients were progressive at
      enrolment. Partial and complete responses occurred in 15 of 46 (32.6%) assessable
      patients. The median time to progression was 36 months. Overall survival was 68%
      at 36 months. Non-responders and patients with extensive tumour involvement had
      lower survival. CONCLUSION: (177)Lu-DOTATATE was well tolerated up to 29 GBq
      cumulative activity (up to 7.4 GBq/cycle). The maximum tolerated dose/cycle was
      not reached. However, considering the individual bone marrow function and the
      presence of risk factors for kidney toxicity, it seems safer to divide cumulative
      activities into lower activity cycles.

PMID- 21892624
TI  - Current approaches to micro-RNA analysis and target gene prediction.
AB  - It is becoming increasingly evident that micro-RNAs (miRNA) play a significant
      role in regulating the cellular machinery. These ~22-nt non-coding RNAs function
      as negative regulators of gene expression. Since their discovery, considerable
      information has been obtained on miRNA biology and the mechanism of their action.
      Guidelines have been established for miRNA nomenclature and databases have been
      built to house all miRNA from many species. A number of methodologies are
      available for miRNA analysis. There is a lot of interest in developing
      bioinformatics approaches to predict miRNA target genes. This article will bring
      together the information on our current knowledge of miRNA biology, the
      approaches for miRNA analysis, and computational strategies to gain insight in
      miRNA functional roles.

PMID- 21892625
TI  - Spinocerebellar ataxia: a rational approach to aetiological diagnosis.
AB  - The objective of this study was to determine the main causal diagnosis for
      spinocerebellar ataxia (SCA) in a geographically defined population of ataxia
      patients and to suggest a rational basis for choosing appropriate clinical and
      paraclinical assessments. Given the many aetiologies responsible for SCA, the
      diagnosis requires the performance of a wide range of paraclinical analyses. At
      present, there is no consensus on the diagnostic value of these examinations.
      Furthermore, most of the currently available data gathered by reference centres
      suffer from selection bias. We performed a prospective study of consecutive
      cerebellar ataxia patients referred by their family doctors to a university
      hospital in northern France. Multiple system atrophy and obvious secondary causes
      (e.g. alcoholism) were excluded by our screening process. The patient's family
      members were also assessed. Of the 204 patients examined, 47% presented autosomal
      dominant ataxia and 33% presented sporadic ataxia. Autosomal recessive ataxia was
      rare (8%) and age at onset was significantly earlier for this condition than for
      other forms. An aetiological diagnosis was established in 44% of patients, a
      plausible hypothesis could be formed in 13% of cases, and no diagnosis was made
      in the remaining 44%. Established diagnoses included SCA1, SCA2, SCA3 and SCA6
      mutations, Friedreich's ataxia, and one rare case of ataxia associated with anti
      glutamic acid decarboxylase antibodies. Two families presented ataxia associated
      with autosomal, dominant, optic atrophy with an OPA1 mutation. Mitochondrial
      diseases were suspected in about 10% of patients. In SCA, reliable determination
      of the transmission mode always requires the assessment of family members.
      Mitochondrial disease may be an emerging cause of ataxia. Metabolite assays
      appeared to be of little value when systematically performed and so should be
      prescribed only by metabolic disorder specialists in selected cases of sporadic
      and recessive ataxia. Ophthalmological examination was the most helpful
      physiological assessment.

PMID- 21892626
TI  - Cartilage repair in the rabbit knee: mosaic plasty resulted in higher degree of
      tissue filling but affected subchondral bone more than microfracture technique: a
      blinded, randomized, controlled, long-term follow-up trial in 88 knees.
AB  - PURPOSE: Discrepancies and variances in outcome following different surgical
      techniques for cartilage repair are poorly understood. Successful repair relies
      on proper tissue filling without initiating degenerative processes in the
      cartilage-bone unit. Consequently, the objective of the current study was to
      compare two available techniques for cartilage repair, i.e., microfracture
      technique and mosaic plasty, regarding tissue filling and subchondral bone
      changes in an experimental model. METHODS: A 4-mm pure chondral defect was
      created in the medial femoral condyle of both knees in New Zealand rabbits, aged
      22 weeks. A stereomicroscope was used to optimize the preparation of the defects.
      In one knee (randomized), the defect was treated with microfracture technique
      whereas in the other with mosaic plasty. The animals were killed at 12, 24 and 36
      weeks after surgery. Defect filling, new bone formation above the level of the
      tidemark and the density of subchondral mineralized tissue were estimated by
      histomorphometry. RESULTS: Mosaic plasty resulted in a significantly 34% higher
      degree of tissue filling than microfracture technique at 36 weeks, SD of mean
      difference being 34%. Mosaic plasty resulted in significantly more new bone
      formation and reduced subchondral mineralized tissue density compared to
      microfracture technique. The differences between the two techniques were apparent
      mainly at the long-term follow-up. CONCLUSION: Tissue filling is a limiting
      factor regarding microfracture technique when compared to mosaic plasty, whereas
      mosaic plasty resulted in more bone changes than microfracture technique-the
      implications of the latter remain to be settled. This study underlines the
      difficulty in predicting outcome in the single case with any of these two
      techniques, particularly in a long-term perspective.

PMID- 21892627
TI  - Neonatal exposure to high doses of 17beta-estradiol results in inhibition of
      heparanase-1 expression in the adult prostate.
AB  - Heparanase-1 (HPSE-1) is an endoglycosidase that cleaves heparan sulfate. The
      physiological functions of HPSE-1 include embryo development, hair growth, wound
      healing, tumor growth, angiogenesis, metastasis, and inflammation. HPSE-1
      expression was found to increase temporarily in the rat ventral prostate (VP)
      after castration. The promoter region of the Hpse-1 gene has estrogen-responsive
      elements, suggesting that the gene is regulated by estrogens. In this study, we
      investigated the expression of HPSE-1 in the VP of 90-day-old rats after neonatal
      exposure to a high dose of 17beta-estradiol. HPSE-1 was not found by
      immunohistochemistry in the epithelium of estrogenized animals. To determine
      whether inhibition of Hpse-1 expression in the epithelium was due to pre- or post
      transcriptional regulation, epithelial cells were isolated by centrifugation in
      Percoll gradient and the presence of Hpse-1 mRNA was investigated by RT-PCR. Hpse
      1 mRNA was not detected in the estrogenized animals. Considering that Hpse-1
      transcription could be inhibited by DNA methylation, we used the methylation
      sensitive restriction enzyme HpaII and PCR to show that a single CCGG site at
      position +185 was more frequently methylated in the epithelium of estrogenized
      than in control animals. Immunohistochemistry for 5-methylcytidine revealed that
      the epithelial cell nuclei in estrogenized animals were heavily methylated. These
      results suggest that Hpse-1 expression was blocked in the epithelial cells of the
      VP, by estrogen imprinting by a pre-transcriptional mechanism involving DNA
      methylation.

PMID- 21892629
TI  - Multistep liquid-phase lithography for fast prototyping of microfluidic free-flow
      electrophoresis chips.
AB  - We present a fast and versatile method to produce functional micro free-flow
      electrophoresis chips. Microfluidic structures were generated between two glass
      slides applying multistep liquid-phase lithography, omitting troublesome bonding
      steps or cost-intensive master structures. Utilizing a novel spacer-less approach
      with the photodefinable polymer polyethyleneglycol dimethacrylate (PEG-DA),
      microfluidic devices with hydrophilic channels of only 25 MUm in height were
      generated. The microfluidic chips feature ion-permeable segregation walls between
      the electrode channels and the separation bed and hydrophilic surfaces. The
      performance of the chip is demonstrated by free-flow electrophoretic separation
      of fluorescent xanthene dyes and fluorescently labeled amino acids.

PMID- 21892628
TI  - Transcription suppression of SARI (suppressor of AP-1, regulated by IFN) by BCR
      ABL in human leukemia cells.
AB  - The BCR-ABL tyrosine kinase has been implicated in the dysregulation of oncogenes
      and tumor suppressor genes involved in chronic myelogenous leukemia (CML).
      Suppressor of activator protein-1, regulated by interferon (SARI), is a recently
      identified tumor suppressor gene whose expression has been reported to be
      suppressed in several malignant neoplasms. However, the expression of SARI in
      leukemia and the underlying regulatory mechanism remain elusive. In this study,
      we demonstrated that SARI mRNA expression was low in CML patients. In vitro, BCR
      ABL kinase inhibitor imatinib mesylate or siRNA specific to BCR-ABL upregulated
      SARI mRNA expression in human leukemia cells. In addition, JAK/STAT signaling
      inhibitor AG490 and RAS/MAPK signaling inhibitor PD98059 upregulated SARI mRNA
      expression, but PI3K/AKT pathway inhibitor LY294002 had no such effect.
      Functionally, silencing of SARI in CML-derived cell line K562 partially decreased
      imatinib mesylate-induced apoptosis. Taken together, these data demonstrate that
      SARI mRNA expression is suppressed by BCR-ABL through the downstream signaling
      pathways, suggesting SARI as a potential therapeutic target in CML.

PMID- 21892630
TI  - Prevalence of obesity among patients with congenital and acquired heart disease.
AB  - Overweight and obesity rates have risen dramatically in the United States, with
      subsequent detrimental comorbidity risks. The rates for obesity among children
      with congenital and acquired heart disease have rarely been reported. A
      retrospective cross-sectional study was conducted to determine the prevalence of
      overweight and obesity in children with heart disease and to identify subgroups
      at increased risk. A total of 795 cases were identified from a chart review of
      patients presenting to an urban center's Pediatric Cardiology Program between 1
      January and 31 December 2006. A body mass index (BMI) at the 85th percentile or
      higher was defined as overweight, and a BMI at the 95th percentile or higher was
      defined as obese. Subjects with comorbidities affecting body habitus were
      excluded from the study. Overall, overweight and obesity rates were similar to
      national data. No significant differences in overweight or obesity rates were
      detected between heart disease and non-heart disease groups (P = 0.50). According
      to multivariate analysis, Hispanic ethnicity and male gender were the only
      predictors of obesity. This study shows that children with heart disease are not
      immune to the common predictors of obesity such as gender and ethnicity and that
      the future care of children with heart disease should include general discussions
      about the risks for obesity.

PMID- 21892631
TI  - Effects of motion sickness on thermoregulatory responses in a thermoneutral air
      environment.
AB  - Motion sickness (MS) has been identified as a non-thermal factor that can
      moderate autonomic thermoregulatory responses. It has been shown that MS
      exaggerates core cooling during immersion in cold (15  degrees C) and luke-warm
      (28  degrees C) water by attenuating cold-induced vasoconstriction. The aim of
      the present study was to investigate whether MS affects thermal balance in a
      thermoneutral air environment. Eleven subjects were exposed to rotation in two
      conditions, control (CN) and MS. In the CN condition subjects refrained from head
      movements, whereas in the MS condition they performed a sequence of maximal head
      movements (left, right, up, down) at 15-s intervals until they were very
      nauseous. Sweating rate, rectal temperature (T(re)), the difference in
      temperature between the right forearm and tip of the second finger (T(ff)) as an
      index of cutaneous vasomotor tone, perceived MS, thermal comfort and temperature
      perception were recorded before and during rotation, and during 90-min post
      rotation. During the post-rotation period, T(re) dropped and sweating rate
      increased in the MS but not in the CN condition. The T(ff) response suggests that
      MS-induced peripheral vasodilatation which, together with the sweating resulted
      in increased heat loss. During rotation, subjects perceived temperature to be
      uncomfortably high, suggesting that MS may also affect thermoregulatory
      behaviour. It thus appears that also in a thermoneutral air environment MS may
      substantially affect thermal balance.

PMID- 21892632
TI  - Radioprotection by the histone deacetylase inhibitor phenylbutyrate.
AB  - The histone deacetylase inhibitor (HDAC), phenylbutyrate (PB), is a novel anti
      tumor agent. Studies have demonstrated that HDAC inhibitors can suppress
      cutaneous radiation syndrome and stimulate hematopoiesis. The objective of this
      study was to test the ability of PB treatment to protect against acute gamma
      radiation-induced lethality in the DBA/2 mouse model. A 30-day radiation
      lethality study was used to assess radioprotective capability of PB. Mechanisms
      were evaluated using western blots, flow cytometry, and the single-cell gel
      electrophoresis assay. Western blot studies showed that PB treatment acetylated
      histones in vivo. For radiation protection studies, prophylactic administration
      of PB (24 h preradiation; 1-50 mg/kg) provided radioprotection against gamma
      radiation (8-9.5 Gy) and PB demonstrated a DRF of 1.31 (P = 0.001; 95% confidence
      interval: 1.27, 1.36). When PB (10 mg/kg) was administered post-radiation (4 h),
      it also provided significant radioprotection at 8.0 Gy radiation (P = 0.022). PB
      treatment before radiation was associated with significant elevations in
      neutrophils and platelets following radiation. Results from single-cell gel
      electrophoresis of peripheral blood leukocytes demonstrated that PB treatment
      before radiation can attenuate DNA damage and inhibit radiation-induced
      apoptosis. These results indicate that an HDAC inhibitor like PB has potential as
      a radiation protector and that mechanisms of action include attenuation of DNA
      damage and inhibition of apoptosis.

PMID- 21892634
TI  - Emergent carotid artery stenting using a flow reversal system for acute
      atherosclerotic occlusion of the internal carotid artery.

PMID- 21892633
TI  - A gyrB-targeted PCR for rapid identification of Salmonella.
AB  - Salmonella causes the majority of infections in humans and homeothermic animals.
      This article describes a specific polymerase chain reaction (PCR) method
      developed for a rapid identification of Salmonella. A gyrB-targeted species
      specific primer pair, S-P-for (5'-GGT GGT TTC CGT AAA AGT A-3') and S-P-rev (5'
      GAA TCG CCT GGT TCT TGC-3'), was successfully designed. PCR with all the
      Salmonella strains produced a 366- bp DNA fragment that was absent from all the
      non-Salmonella strains tested. The detection limit of the PCR was 0.01 ng with
      genomic DNA or 3.2 cells per assay. Good specificity was also demonstrated by
      fecal samples, from which only the gyrB gene of Salmonella was amplified. Using
      the culture-PCR method, 27 isolates on Salmonella-Shigella (SS) medium were
      rapidly identified as Salmonella, which was confirmed by the sequencing of the
      gyrB gene.

PMID- 21892635
TI  - Bilateral primary optic nerve sheath meningiomas with pneumosinus dilatans.

PMID- 21892636
TI  - Pilocytic astrocytoma originating at the cavernous sinus.
AB  - We report a case of histologically proven pilocytic astrocytoma arising within
      the cavernous sinus, confirmed radiographically and at operation. We discuss the
      implications in the context of previous reports of ectopic glioma origin. In
      particular, the possiblity of glioma development within glial cell islands in the
      peripheral segment of cranial nerves is explored.

PMID- 21892637
TI  - Accuracy of external ventricular drainage catheter placement.
AB  - BACKGROUND: External ventricular drainage (EVD) is a freehand neurosurgical
      procedure performed routinely using the anatomical landmarks. OBJECTIVE: The aim
      of this study was to determine the accuracy of EVD catheter freehand placement.
      MATERIALS AND METHODS: Pre-operative and post-operative computed tomography scans
      for 66 consecutive EVDs performed in 56 adult patients (26 men, 30 women) in 2008
      were retrospectively reviewed. Etiologies of acute hydrocephalus were
      subarachnoid or intraventricular haemorrhage (43 cases) or miscellaneous (13
      cases). Pre-operative lateral ventricular volume, position of the burr hole,
      length of the catheter and its sagittal and coronal angular variations from a
      theoretical trajectory were measured. RESULTS: The EVD was placed on the right
      (53 cases) or left (13 cases) side. The mean pre-operative lateral ventricular
      volume was 51 cc (10-118 cc). The average distance from the burr hole to the
      midline was 28 mm (10-49 mm) and to the supra-orbital ridge was 101 mm (75-125
      mm). The mean intracranial catheter length was 60 mm (from 39-102 mm). Only 50%
      of the EVDs in the coronal plane and 40% in the sagittal plane were placed with
      an angular variation of +/-5 degrees  to the target. The tip was placed outside
      of the ventricles in three cases; 13 catheters crossed the midline, and five
      intracranial minor haemorrhages were detected. CONCLUSION: Freehand placement of
      EVDs does not have sufficient accuracy and may lead to drainage dysfunctions.
      This data suggests that a guidance system for EVD's would be required.

PMID- 21892638
TI  - Measurement of 3-hydroxyisovaleric acid in urine from marginally biotin-deficient
      humans by UPLC-MS/MS.
AB  - Measurement of 3-hydroxyisovaleric acid (3HIA) in human urine has been shown to
      be a useful indicator of biotin status for a variety of clinical situations,
      including pregnancy. The work described herein presents a novel UPLC-MS/MS method
      for accurate and precise quantitation of urinary 3HIA. This method utilizes
      sample preparation prior to quantitation that has been simplified compared to the
      previous GC-MS method. To demonstrate the suitability of the UPLC-MS/MS method
      for human bio-monitoring, this method was used to measure 3-HIA in 64 human urine
      samples from eight healthy adults in whom marginal biotin deficiency had been
      induced experimentally by egg white feeding. 3HIA was detected in all specimens;
      the mean concentration [+/-standard deviation (SD)] was 80.6 +/- 51 MUM prior to
      inducing biotin deficiency. Mean excretion rate for 3HIA (expressed per mol
      urinary creatinine) before beginning the biotin-deficient diet was 8.5 +/- 3.2
      mmol 3HIA per mol creatinine and the mean increased threefold with deficiency.
      These specimens had been previously analyzed by GC-MS; the two data sets showed
      strong linear relationship with a correlation coefficient of 0.97. These results
      provide evidence that this method is suitable for bio-monitoring of biotin status
      in larger populations.

PMID- 21892639
TI  - Simultaneous LC-MS/MS determination of aflatoxin M1, ochratoxin A,
      deoxynivalenol, de-epoxydeoxynivalenol, alpha and beta-zearalenols and fumonisin
      B1 in urine as a multi-biomarker method to assess exposure to mycotoxins.
AB  - Humans and animals can be simultaneously exposed through the diet to different
      mycotoxins, including aflatoxins, ochratoxin A, deoxynivalenol, zearalenone, and
      fumonisins, which are the most important. Evaluation of the frequency and levels
      of human and animal exposure to these mycotoxins can be performed by measuring
      the levels of the relevant biomarkers in urine. Available data on the
      toxicokinetics of these mycotoxins in animals suggest that aflatoxin M(1)
      (AFM(1)), ochratoxin A (OTA), deoxynivalenol (DON)/de-epoxydeoxynivalenol (DOM
      1), alpha-zearalenol (alpha-ZOL)/beta-zearalenol (beta-ZOL), and fumonisin B(1)
      (FB(1)) can be used as urinary biomarkers. A liquid chromatographic-tandem mass
      spectrometric method has been developed for simultaneous determination of these
      mycotoxin biomarkers in human or animal urine. Urine samples were purified and
      concentrated by a double cleanup approach, using a multitoxin immunoaffinity
      column and a reversed-phase SPE Oasis HLB column. Separation of the biomarkers
      was performed by reversed-phase chromatography using a multi-step linear methanol
      water gradient containing 0.5% acetic acid as mobile phase. Detection and
      quantification of the biomarkers were performed by triple quadrupole mass
      spectrometry (LC-ESI-MS/MS). The clean-up conditions were optimised to obtain
      maximum analyte recovery and high sensitivity. Recovery from spiked samples was
      performed at four levels in the range 0.03-12 ng mL(-1), using matrix-matched
      calibration curves for quantification. Mean recoveries of the biomarkers tested
      ranged from 62 to 96% with relative standard deviations of 3-20%. Enzymatic
      digestion with beta-glucuronidase/sulfatase resulted in increased concentrations
      of the biomarkers, in both human and pig urine, in most samples containing
      measurable concentrations of DON, DOM-1, OTA, alpha-ZOL, or beta-ZOL. A highly
      variable increase was observed between individuals. Co-occurrence of OTA and DON
      in human urine is reported herein for the first time.

PMID- 21892640
TI  - Ca(2+)-triggered coelenterazine-binding protein from Renilla as an enzyme
      dependent label for binding assay.
AB  - The recombinant Ca(2+)-triggered coelenterazine-binding protein (CBP) from
      Renilla muelleri was investigated as a biospecifically labeled molecule for in
      vitro assay applications. The protein was shown to be stable in solutions in the
      frozen state, as well as stable under heating and to chemical modifications.
      Conjugates with biotin, oligonucleotide, and proteins were obtained and applied
      as biospecific molecules in a solid-phase microassay. CBP detection was performed
      with intact (no modifications were made) Renilla luciferase in the presence of
      calcium, and the detection limit was found to be 75 amol. Model experiments
      indicate that this approach shows much promise, especially with regard to the
      development of multianalytical systems.

PMID- 21892641
TI  - Quantitative analysis of eletriptan in human plasma by HPLC-MS/MS and its
      application to pharmacokinetic study.
AB  - Authors developed a simple, sensitive, selective, rapid, rugged, and reproducible
      liquid chromatography-tandem mass spectrometry method for the quantification of
      eletriptan (EP) in human plasma using naratriptan (NP) as an internal standard
      (IS). Chromatographic separation was performed on Ascentis Express C18, 50 * 4.6
      mm, 2.7 MUm column. Mobile phase was composed of 0.1% formic acid: methanol
      (40:60 v/v), with 0.5 mL/min flow rate. Drug and IS were extracted by liquid
      liquid extraction. EP and NP were detected with proton adducts at m/z 383.2->84.3
      and 336.2->97.8 in multiple reaction monitoring (MRM) positive mode,
      respectively. The method was validated with the correlation coefficients of
      (r(2)) >= 0.9963 over a linear concentration range of 0.5-250.0 ng/mL. This
      method demonstrated intra- and inter-day precision within 1.4-9.2% and 4.4-5.5%
      and accuracy within 96.8-103% and 98.5-99.8% for EP. This method is successfully
      applied in the bioequivalence study of 24 human volunteers.

PMID- 21892642
TI  - Electrochemical sensor for blood deoxyribonucleases: design and application to
      the diagnosis of autoimmune thyroiditis.
AB  - We designed an electrochemical sensor based on a carbon nanotube modified
      electrode (ME) to analyze DNA-cleaving activity. The cleavage of high molecular
      weight DNA resulted in an increase in the oxidation current from DNA guanine
      nucleotides due to a change in DNA adsorptive behavior on the surface of the ME.
      DNA digestion with DNAse I was accompanied by a linear increase in the DNA signal
      in proportion to the enzyme activity. We then proposed an assay based on the
      sensor for the direct assessment of the total deoxyribonuclease activity of blood
      serum as well as the separate detection of DNAse I and DNA abzymes. The assay was
      applied to analyze deoxyribonucleases in sera from 21 healthy donors and 17
      patients with autoimmune thyroiditis. Our results show that the response of the
      sensor to DNA cleavage by blood deoxyribonucleases is a promising diagnostic
      criterion for autoimmune thyroiditis. This sensor can be implemented in a
      disposable screen-printed electrode format for application in clinical
      laboratories.

PMID- 21892643
TI  - The impact of obesity on cardiac troponin levels after prolonged exercise in
      humans.
AB  - Elevated cardiac troponin I (cTnI), a marker for cardiac damage, has been
      reported after high-intensity exercise in healthy subjects. Currently, little is
      known about the impact of prolonged moderate-intensity exercise on cTnI release,
      but also the impact of obesity on this response. 97 volunteers (55 men and 42
      women), stratified for BMI, performed a single bout of walking exercise (30-50
      km). We examined cTnI-levels before and immediately after the exercise bout in
      lean (BMI < 25 kg/m(2), n = 30, 57 +/- 19 years), overweight (25 <= BMI < 30
      kg/m(2), n = 29, 56 +/- 11 years), and obese subjects (BMI >= 30 kg/m(2), n = 28,
      53 +/- 9 years). Walking was performed at a self-selected pace. cTnI was assessed
      using a high-sensitive cTnI-assay (Centaur; clinical cut-off value >= 0.04
      MUg/L). We recorded subject characteristics (body weight, blood pressure,
      presence of cardiovascular risk) and examined exercise intensity by recording
      heart rate. Mean cTnI-levels increased significantly from 0.010 +/- 0.006 to
      0.024 +/- 0.046 MUg/L (P < 0.001). The exercise-induced increase in cTnI was not
      different between lean, overweight and obese subjects (two-way ANOVA interaction;
      P = 0.27). In 11 participants, cTnI was elevated above the clinical cut-off value
      for myocardial infarction. Logistic regression analysis identified exercise
      intensity (P < 0.001), but not BMI, body fat percentage or waist circumference to
      significantly relate to positive troponin tests. In conclusion, prolonged,
      moderate-intensity exercise results in a comparable increase in cTnI-levels in
      lean, overweight and obese subjects. Therefore, measures of obesity unlikely
      relate to the magnitude of the post-exercise elevation in cTnI.

PMID- 21892644
TI  - Cognitive function following treadmill exercise in thermal protective clothing.
AB  - Occupational injuries are common among firefighters who perform strenuous
      physical exertion in extreme heat. The thermal protective clothing (TPC) worn by
      firefighters inhibits normal thermoregulation, placing the firefighter at risk of
      hypohydration and hyperthermia that may result in cognitive decline. We tested
      whether cognitive function changes after treadmill exercise in TPC. In an initial
      study (Cog 1), ten healthy volunteers performed up to 50 min of treadmill
      exercise while wearing TPC in a heated room. A battery of neurocognitive tests
      evaluating short-term memory, sustained and divided attention, and reaction time
      was administered immediately before and after exercise. In a follow-up study (Cog
      2), 19 healthy volunteers performed a similar exercise protocol with the battery
      of cognitive tests administered pre-exercise, immediately post-exercise, and
      serially up to 120 min after exercise. Subjects performed 46.4 +/- 4.6 and 48.1
      +/- 3.6 min of exercise in the Cog 1 and Cog 2, respectively. In both studies
      heart rate approached age predicted maximum, body mass was reduced 1.0-1.5 kg,
      and body core temperature increased to levels similar to what is seen after fire
      suppression. Neurocognitive test scores did not change immediately after
      exercise. Recall on a memory test was reduced 60 and 120 min after exercise. The
      mean of the 10 slowest reaction times increased in the 120 min after exercise.
      Fifty minutes of treadmill exercise in TPC resulted in near maximal physiologic
      strain but alterations in neurocognitive performance were not noted until an hour
      or more following exercise in TPC.

PMID- 21892645
TI  - [Monitoring a melanocytic tumor. When is excision indicated?].
AB  - Follow-up examination with comparison of dermoscopic images was performed over 24
      months on an initially unimpressive, distinctly asymmetrical melanocytic tumor in
      a 39-year-old woman. She did not follow the recommendation for an excision after
      19 months and 5 months later she came back for the next follow-up image. At this
      stage she was pregnant. The dermoscopic suspicion of a melanoma in-situ was
      confirmed by histology. This case is instructive in the view of follow-up, self
      examination, self- detection of a melanoma, asymmetric changes of melanocytic
      lesion and evaluation of changes during pregnancy.

PMID- 21892646
TI  - [Immunology of contact allergy].
AB  - Contact allergy is a skin disease that is caused by the reaction of the immune
      system to low molecular weight chemicals. A hallmark of contact allergens is
      their chemical reactivity, which is not exhibited by toxic irritants. Covalent
      binding of contact allergens to or complex formation with proteins is essential
      for the activation of the immune system. As a consequence antigenic epitopes are
      formed, which are recognized by contact allergen-specific T cells. The generation
      of effector and memory T cells causes the high antigen specificity and the
      repeated antigen-specific skin reaction of contact allergy. New findings reveal
      that the less specific reaction of the innate immune system to contact allergens
      closely resembles the reaction to an infection. Therefore, contact allergy can be
      viewed as an immunologic misunderstanding since the skin contact with chemical
      allergens is interpreted as an infection. The growing understanding of the
      molecular and cellular pathologic mechanisms of contact allergy can aid the
      development of specific therapies and of in vitro alternatives to animal testing
      for the identification of contact allergens.

PMID- 21892647
TI  - Diet-induced obesity blunts the behavioural effects of ghrelin: studies in a
      mouse-progressive ratio task.
AB  - RATIONAL: The ghrelinergic system is implicated in the development of obesity and
      in modulating central reward systems. It has been reported that diet-induced
      obesity causes blunted responding on food intake to ghrelin administration,
      associated with central ghrelin resistance. Here we investigate whether the
      stimulatory effects of ghrelin on the reward system are altered in diet-induced
      obese mice. METHODS: Obesity was induced in C57BL/6J mice by feeding high-fat
      diet for 13 weeks. Mice were trained in an operant fixed and exponential
      progressive ratio task to respond for sucrose rewards. In an ad libitum fed
      state, ghrelin and a ghrelin receptor antagonist were administered in the
      progressive ratio. Alterations in the central ghrelin system in diet-induced
      obese mice were assessed. RESULTS: Obese mice showed attenuated acquisition and
      performance in the fixed and progressive ratio paradigm. Most importantly, diet
      induced obesity inhibited the stimulatory effects of ghrelin (2 nmol, 3 nmol/10
      g) on progressive ratio responding whereas lean animals presented with increased
      responding. Administration of the ghrelin-receptor antagonist (D-Lys(3))-GHRP-6
      (66.6 nmol/10 g) decreased performance in lean but not obese mice. This
      insensitivity to ghrelin receptor ligands in mice on high-fat diet was further
      supported by decreased mRNA expression of the ghrelin receptor in the
      hypothalamus and the nucleus accumbens in obese mice. CONCLUSIONS: This study
      demonstrates that the modulatory effects of ghrelin receptor ligands are blunted
      in a mouse model of diet-induced obesity in a progressive ratio task. Thereby,
      our data extend the previously described ghrelin resistance in these mice from
      food intake to reward-associated behaviours.

PMID- 21892648
TI  - Cryo-balloon angioplasty for pulmonary vein stenosis in pediatric patients.
AB  - This study sought to determine the safety and effectiveness of cryo-balloon
      angioplasty (CbA) for pulmonary vein stenosis (PVS) in pediatric patients.
      Current therapy options for PVS are less than satisfactory due to recurrent
      progressive restenosis and neointimal proliferation. Catheterization database,
      hospital records, imaging studies, and pathologic specimens were reviewed for
      procedural-related and outcomes data in all patients who underwent pulmonary vein
      (PV) CbA using the Boston Scientific PolarCath Peripheral Dilation System between
      August 2006 and June 2009. Thirteen patients (19 PVs; median age 13 months [range
      3.5 months to 18.5 years] and weight 7.9 kg [range 3.8 to 47.7]) underwent CbA.
      Mean PVS diameter after CbA increased from 2.19 (+/- 0.6) to 3.77 (+/- 1.1) mm (p
      < 0.001). Mean gradient decreased from 14 (+/- 7.4) to 4.89 (+/- 3.2) mm Hg (p <
      0.001). Mean stenosis-to-normal vein diameter ratio increased from 0.52 (+/-
      0.15) to 0.89 (+/- 0.33) (p < 0.001). Eight patients underwent repeat
      catheterization a mean of 5.6 months (+/- 3.66) later. Improved PVS diameter was
      maintained in 2 PVs. Four veins had restenosis but maintained diameters greater
      than that before initial CbA. In 11 PVs, the diameter decreased from 4.28 (+/-
      1.14) to 2.53 (+/- 0.9) mm (p = 0.001). Mean gradient increased from 3.55 (+/-
      3.0) to 14.63 (+/- 9.6) mm Hg (p = 0.011). All vessels underwent repeat
      intervention with acute relief of PVS. Stroke occurred within 24 h of CbA in 1
      patient. CbA of PVS is safe and results in acute relief of stenosis. However, CbA
      appears minimally effective as the sole therapy in maintaining long-term relief
      of PVS.

PMID- 21892649
TI  - Near infrared spectroscopy describes physiologic payback associated with excess
      postexercise oxygen consumption in healthy controls and children with complex
      congenital heart disease.
AB  - Exercise creates a physiologic burden with recovery from such effort crucial to
      adaptation. Excess postexercise oxygen consumption (EPOC) refers to the body's
      increased metabolic need after work. This investigation was designed to determine
      the role of near infrared spectroscopy (NIRS) in the description of exercise
      recovery in healthy controls (NL) and children with congenital heart disease
      (CHD). Subjects were recruited with exercise testing performed to exhaustion.
      Exercise time (EXT), heart rate (HR), and oxygen consumption (VO(2)) were
      measured. Four-site NIRS (brain, kidney, deltoid, and vastus lateralis) were
      measured during exercise and into recovery to establish trends. Fifty individuals
      were recruited for each group (NL = 26 boys and 24 girls; CHD = 33 boys and 17
      girls). Significant differences existed between EXT, VO(2), and peak HR (P <
      0.01). NIRS values were examined at four distinct intervals: rest, peak work, and
      2 and 5 min after exercise. Significant cerebral hyperemia was seen in children
      with CHD post exercise when compared to normal individuals in whom redistribution
      patterns were directed to somatic muscles. These identified trends support an
      immediate compensation of organ systems to re-establish homeostasis in peripheral
      beds through enhanced perfusion. Noninvasive NIRS monitoring helps delineate
      patterns of redistribution associated with EPOC in healthy adolescents and
      children with CHD.

PMID- 21892650
TI  - Multiple risk factors before pediatric cardiac transplantation are associated
      with increased graft loss.
AB  - Identification of heart transplant recipients at highest risk for a poor outcome
      could lead to improved posttransplantation survival. A chart review of primary
      heart transplantations from 1993 to 2006 was performed. Analysis was performed to
      evaluate the risk of graft loss for those with a transplantation age less than 1
      year, congenital heart disease (CHD), elevated pulmonary vascular resistance
      (index > 6), positive panel reactive antibody or crossmatch, liver or renal
      dysfunction, mechanical ventilation, or mechanical circulatory support (MCS).
      Primary transplantation was performed for 189 patients. Among these patients, 37%
      had CHD, 23% had mechanical ventilation, and 6% had renal dysfunction. Overall
      graft survival was 82% at 1 year and 68% at 5 years. The univariate risk factors
      for graft loss included mechanical ventilation (hazard ratio [HR], 1.9; 95%
      confidence interval [CI], 1.15-3.18), CHD (HR, 1.68; 95% CI, 1.04-2.70), and
      renal dysfunction (HR, 3.05; 95% CI, 1.34-6.70). The multivariate predictors of
      graft loss were CHD (HR, 1.8; 95% CI, 1.02-2.64), mechanical ventilation (HR,
      1.9; 95% CI, 1.13-3.10), and the presence of two or more statistically
      significant univariate risk factors (SRF) (HR, 3.8; 95% CI, 2.00-7.32).
      Mechanical ventilation, CHD, and the presence of two or more SRFs identify
      pediatric patients at higher risk for graft loss and should be considered in the
      management of children with end-stage heart failure.

PMID- 21892651
TI  - Restrictive physiology is associated with poor outcomes in children with
      hypertrophic cardiomyopathy.
AB  - Pediatric patients with hypertrophic cardiomyopathy (HCM) and restrictive
      physiology (RP) with poor outcomes have been identified, but data on their course
      are limited. Our goal was to delineate the clinical features and course of
      children with HCM and RP. An institutional review of 119 patients identified
      between 1985 and 2010 with the diagnosis of HCM was performed. The diagnosis of
      RP was based on >1 echocardiogram along with at least one of the following: left
      atrial enlargement without evidence of left ventricle dilation, E/E' ratio >= 10,
      and E/A ratio >= 3. Outcomes analysis was performed using Cox or Poisson
      regression when appropriate. RP was present in 50 (42%) patients. In patients
      without RP, 10-year freedom-from-death or aborted sudden cardiac death (aSCD),
      and death or heart transplant (HT), were 93.6 and 98.5%, respectively. In
      patients with RP, 10-year freedom-from-death or aSCD, and death or HT, were 59.0
      and 71.2%, respectively. RP conferred a 3.5-fold increase in incidence rate of
      hospitalization (P = 0.01), a 3.8-fold increase in hazard of death or aSCD (P =
      0.02), and a 5.7-fold increase in hazard of death or HT (P = 0.04). Assessment
      for RP is of paramount importance in children with HCM because those without RP
      have a good prognosis, and those with RP account for the majority of poor
      outcomes.

PMID- 21892652
TI  - BMP9 inhibits the proliferation and invasiveness of breast cancer cells MDA-MB
      231.
AB  - BACKGROUND: Transforming growth factor-beta (TGF-beta) is known to promote tumor
      proliferation, migration, invasion, and metastasis. Bone morphogenetic proteins
      (BMPs) are members of the TGF-beta superfamily. Several BMPs (BMP2 and BMP7) can
      enhance the invasion and bone metastasis of breast cancer cells. The function of
      BMP9, the latest discovered and most powerful osteogenetic factor, in breast
      cancer has not been fully elucidated. METHODS: BMP9 expression in twenty-three
      breast cancer patients and three breast cancer cell line types was detected by
      reverse transcriptase polymerase chain reaction. Changes in proliferation,
      apoptosis, invasion, and migration in the recombinant MDA-MB-231/BMP9 cells were
      detected using various assays. The assays were MTT, flow cytometry, colony
      forming, cell wounding, and transwell invasion. Proliferating cell nuclear
      antigen and terminal deoxynucleotidy transferase biotin-dUTP nick end labeling
      staining methods were conducted to detect whether BMP9 affected proliferation and
      apoptosis in xenogenic mouse models. RESULTS: Twenty-one of the twenty-three
      breast cancer patients had amplified BMP9 mRNA transcripts in adjacent non-tumor
      tissues, although BMP9 was observed in the breast cancer tissue of two patients,
      its expression was higher in the adjacent non-tumor tissues. BMP9 overexpression
      inhibited the proliferation, migration, and invasion, as well as induced the
      apoptosis of the breast cancer cell line MDA-MB-231 in vitro. BMP9 also inhibited
      tumor growth and induced apoptosis significantly in the xenogenic mouse models.
      CONCLUSIONS: Decreased BMP9 expression is associated with the elevated
      proliferation and migration of human breast cancer. BMP9 can inhibit the growth,
      invasion, and migration of breast cancer cells in vitro and in vivo. BMP9 is a
      putative tumor suppressor in breast cancer.

PMID- 21892653
TI  - Successful treatment of azole-resistant Candida spondylodiscitis with high-dose
      caspofungin monotherapy.

PMID- 21892654
TI  - Rituximab-induced pulmonary disease.

PMID- 21892655
TI  - Generalized anhidrosis in a child following presumptive H1N1 influenza.
AB  - We report an 8-year-old girl who developed generalized anhidrosis following
      presumptive H1N1 infection. Pure autonomic dysfunction is an unusual complication
      following H1N1 infection and specially generalized anhidrosis without other
      autonomic dysfunction have not been reported before.

PMID- 21892656
TI  - Outcomes and general health-related quality of life among patients medically
      treated in general daily practice for lower urinary tract symptoms due to benign
      prostatic hyperplasia.
AB  - OBJECTIVE: This study's aim was to describe and evaluate outcomes of medical
      strategies used for lower urinary tract symptoms (LUTS) treatment in general
      practice and to assess impact of LUTS on patients' general health-related quality
      of life (HRQoL). METHODS: This cross-sectional observational study was conducted
      by French general practitioners. Eligible patients were males aged >=50 years,
      diagnosed for at least one year and currently treated for LUTS due to benign
      prostatic hyperplasia (BPH). Several validated questionnaires were documented by
      patients to assess severity of LUTS (IPSS), specific quality of life (IPSS-Q8),
      impact of LUTS (BII), LUTS evolution (VNS) and general HRQoL (EQ-5D). RESULTS:
      Among 1,098 patients included, 82.7% were treated with monotherapies and 17.3%
      with combinations. Mean treatment duration was 5.2 +/- 3.2 years, and 47.2% of
      patients had at least one treatment modification since initiation. Patients
      reported diminished quality of life (IPSS-Q8 >=3) (42.3%), persisting symptoms
      (IPSS-score >=12) (35.5%), symptoms worsening (VNS-score <=-1) (18.8%) and high
      bother (BII-score >=9) (2.6%). Globally, 52.8% had at least one of these
      unsatisfactory outcomes. Regarding general HRQoL, mean EQ-5D utility
      significantly decreased with LUTS severity (mild: 0.90 +/- 0.12; moderate: 0.81
      +/- 0.21; and severe symptoms: 0.73 +/- 0.25; P < 0.001). As well, all five
      dimensions of EQ-5D were significantly altered in patients with moderate-to
      severe LUTS (<0.001), especially 'Pain/Discomfort' and 'Anxiety/Depression'. In
      multivariate analyses including age and comorbidities, EQ-5D utility index
      remained negatively associated with each additional unit in the IPSS-score.
      CONCLUSIONS: This study shows that around half of BPH patients medically treated
      report unsatisfactory outcomes, suggesting consequential unmet medical needs in
      general practice. Also, moderate-to-severe LUTS significantly impact on general
      HRQoL.

PMID- 21892657
TI  - CETP polymorphisms associate with brain structure, atrophy rate, and Alzheimer's
      disease risk in an APOE-dependent manner.
AB  - Two alleles in cholesteryl ester transfer protein (CETP) gene polymorphisms have
      been disputably linked to enhanced cognition and decreased risk of Alzheimer's
      disease (AD): the V and A alleles of I405V and C-629A. This study investigates
      whether these polymorphisms affect brain structure in 188 elderly controls and
      318 AD or mild cognitive impairment (MCI) subjects from the Alzheimer's Disease
      Neuroimaging Initiative cohort. Nominally signficant associations were dependent
      on APOE epsilon4 carrier status. In APOE epsilon4 carriers, the V and A alleles,
      both of which decrease CETP and increase HDL, associated with greater baseline
      cortical thickness and less 12-month atrophy in the medial temporal lobe.
      Conversely, in APOE epsilon4 non-carriers, the I allele, which increases CETP and
      decreases HDL, associated with greater baseline thickness, less atrophy and lower
      risk of dementia. These results suggest CETP may contribute to the genetic
      variability of brain structure and dementia susceptibility in an APOE-dependent
      manner.

PMID- 21892660
TI  - Symptoms of anxiety and cardiac hospitalizations at 12 months in patients with
      heart failure.
AB  - OBJECTIVE: Heart failure (HF) is a leading cause of hospitalization. Clinical and
      socio-demographic factors have been associated with cardiac admissions, but
      little is known about the role of anxiety. We examined whether symptoms of
      anxiety were associated with cardiac hospitalizations at 12 months in HF
      patients. METHODS: HF outpatients (N = 237) completed the Hospital Anxiety and
      Depression Scale (HADS) at baseline (i.e., inclusion into the study). A cutoff
      >=8 was used to indicate probable clinical levels of anxiety and depression. At
      12 months, a medical chart abstraction was performed to obtain information on
      cardiac hospitalizations. RESULTS: The prevalence of symptoms of anxiety was
      24.9% (59/237), and 27.0% (64/237) of patients were admitted for cardiac reasons
      at least once during the 12-month follow-up period. Symptoms of anxiety were
      neither significantly associated with cardiac hospitalizations in univariable
      logistic analysis [OR = 1.13, 95% CI (0.59-2.17), p = 0.72] nor in multivariable
      analysis [OR = 0.94, 95% CI (0.38-2.31), p = 0.89]. New York Heart Association
      (NYHA) functional class III [OR = 3.00, 95% CI (1.08-8.12), p = 0.04] and a
      history of HF-related hospitalizations [OR = 1.18, 95% CI (1.01-1.38), p = 0.03]
      were independently associated with 12-month cardiac admissions. CONCLUSIONS: The
      current study found no significant association between symptoms of anxiety and
      cardiac hospitalizations at 12 months in HF patients. In contrast, clinical
      indicators (i.e., NYHA class III and a history of HF-related hospitalizations)
      were significantly associated with admissions due to a cardiac cause. Future
      studies are warranted to investigate the importance of symptoms of anxiety in HF
      using a larger sample size and a longer follow-up duration.

PMID- 21892661
TI  - Changes in disparities following the implementation of a health information
      technology-supported quality improvement initiative.
AB  - BACKGROUND: Health information technology (HIT)-supported quality improvement
      initiatives have been shown to increase ambulatory care quality for several
      chronic conditions and preventive services, but it is not known whether these
      types of initiatives reduce disparities. OBJECTIVES: To examine the effects of a
      multifaceted, HIT-supported quality improvement initiative on disparities in
      ambulatory care. DESIGN: Time series models were used to assess changes in racial
      disparities in performance between white and black patients for 17 measures of
      chronic disease and preventive care from February 2008 through February 2010, the
      first 2 years after implementation of a HIT-supported, provider-directed quality
      improvement initiative. PATIENTS: Black and white adults receiving care in an
      academic general internal medicine practice in Chicago. INTERVENTIONS: The
      quality improvement initiative used provider-directed point-of-care clinical
      decision support tools and quality feedback to target improvement in process of
      care and intermediate outcome measures for coronary heart disease, heart failure,
      hypertension, and diabetes as well as receipt of several preventive services.
      MAIN MEASURES: Modeled rate of change in performance, stratified by race and
      modeled rate of change in disparities for 17 ambulatory care quality measures KEY
      RESULTS: Quality of care improved for 14 of 17 measures among white patients and
      10 of 17 measures among black patients. Quality improved for both white and black
      patients for five of eight process of care measures, four of five preventive
      services, but none of the four intermediate outcome measures. Of the seven
      measures with racial disparities at baseline, disparities declined for two,
      remained stable for four, and increased for one measure after implementation of
      the quality improvement initiative. CONCLUSIONS: Generalized and provider
      directed quality improvement initiatives can decrease racial disparities for some
      chronic disease and preventive care measures, but achieving equity in areas with
      persistent disparities will require more targeted, patient-directed, and systems
      oriented strategies.

PMID- 21892662
TI  - Effects of physical exercise on spatial memory and astroglial alterations in the
      hippocampus of diabetic rats.
AB  - Type 1 diabetes mellitus (T1DM) is associated with neurocognitive dysfunction and
      astrogliosis. Physical exercise prevents cognitive impairments and induces
      important brain modifications. The aim of our study was to investigate the effect
      of treadmill exercise on spatial memory and astrocytic function in the
      hippocampus of a T1DM model. Fifty-seven Wistar rats were divided into four
      groups: trained control (TC) (n = 15), non-trained control (NTC) (n = 13),
      trained diabetic (TD) (n = 14) and non-trained diabetic (NTD) (n = 15). One month
      after streptozotocin-induced diabetes, exercise groups were submitted to 5 weeks
      of physical training, and then, all groups were assessed in the novel object
      placement recognition task. Locomotor activity was analyzed in the open field
      apparatus using Any-maze software. The expression of glial fibrillary acidic
      protein (GFAP) and S100B in hippocampus and cerebrospinal fluid were measured
      using ELISA assay, and hippocampal GFAP immunoreactivity was evaluated by means
      of immunohistochemistry and optical densitometry. The results showed that
      physical exercise prevents and/or reverts spatial memory impairments observed in
      NTD animals (P < 0.01). Decreased locomotor activity was observed in both the NTD
      and TD groups when compared with controls (P < 0.05). ELISA and
      immunohistochemistry analyzes showed there was a reduction in GFAP levels in the
      hippocampus of NTD animals, which was not found in TD group. ELISA also showed an
      increase in S100B levels in the cerebrospinal fluid from the NTD group (P < 0.01)
      and no such increase was found in the TD group. Our findings indicate that
      physical exercise prevents and/or reverts the cognitive deficits and astroglial
      alterations induced by T1DM.

PMID- 21892663
TI  - Biotransformation of 4-chloro-2-nitrophenol into 5-chloro-2-methylbenzoxazole by
      a marine Bacillus sp. strain MW-1.
AB  - Decolourization, detoxification and biotransformation of 4-chloro-2-nitrophenol
      (4C2NP) by Bacillus sp. strain MW-1 were studied. This strain decolorized 4C2NP
      only in the presence of an additional carbon source. On the basis of thin layer
      chromatography (TLC), high performance liquid chromatography (HPLC) and gas
      chromatography-mass spectrometry (GC-MS), 4-chloro-2-aminophenol, 4-chloro-2
      acetaminophenol and 5-chloro-2-methylbenzoxazole were identified as metabolites.
      Resting cells depleted 4C2NP with stoichiometric formation of 5-chloro-2-methyl
      benzoxazole. This is the first report of the formation of 5-chloro-2
      methylbenzoxazole from 4C2NP by any bacterial strain.

PMID- 21892664
TI  - Effect of biomass adaptation to biodegradation of dissolved organic carbon in
      water.
AB  - In the present study the time of adaptation of fixed biomass for biodegradation
      of natural organic matter was investigated. The experiments were done in columns
      that are usually used for rapid determination of biodegradable dissolved organic
      carbon (BDOC). The biomass was adapted to samples with different concentrations
      of organic substances before measurements by pumping water to be investigated
      through the columns for several days. The time of adaptation was dependent on the
      initial concentration of the organic matter in the water sample. The adaptation
      time increased from 6 to 24 h with increase of concentration of acetate solution
      from 2 to 10 mg/l, thus adaptation rate decreased simultaneously from 0.28 to
      0.11 min(-1). In natural water samples with the initial concentration in the
      range from 4.61-10.82 mg/l of dissolved organic carbon (DOC) the maximal
      adaptation time was less than 24 h. During the adaptation period the increase in
      reproducibility and decrease in the standard deviation was observed. The study
      showed that adaptation of column to the different concentration of organic matter
      in water sample is necessary in order to decrease the bias in BDOC measurements
      when using columns tests.

PMID- 21892665
TI  - Exceptional stability of artemin neurotrophic factor dimers: effects of
      temperature, pH, buffer and storage conditions on protein integrity and activity.
AB  - Artemin (ARTN) is a neurotrophic growth factor of the GDNF ligand family that
      signals through the specific GFRalpha-3 coreceptor/cRet tyrosine kinase-mediated
      signaling cascade. Its expression and signaling action in adults are restricted
      to nociceptive sensory neurons in the dorsal root ganglia. Consequently, Artemin
      supports survival and growth of sensory neurons and has been studied as a
      possible treatment for neuropathic pain. We have developed a robust and sensitive
      cellular assay to measure ARTN biological activity. Using recombinant Artemin
      produced in Escherichia coli bacteria together with this specific assay, we
      demonstrate that ARTN is an exceptionally stable polypeptide. Multiple freeze
      thaw cycles, incubation at elevated temperatures (up to 90  degrees C) for 0.5 h,
      prolonged storage at 4  degrees C, and exposure to conditions of different pH,
      salt concentration, and additives had no measurable effect on the biological
      activity of ARTN. In some of the tested conditions, partial removal of nine NH(2)
      terminal amino acids of the ARTN protein occurred, but this truncation had no
      important effect on the ARTN signaling response. Consequently, we postulate that
      formulation and storage for in vivo testing of ARTN in neuropathic pain paradigms
      in animals and humans should be straightforward.

PMID- 21892666
TI  - Direct and indirect organogenesis of Alpinia galanga and the phytochemical
      analysis.
AB  - Alpinia galanga is a rhizomatous herb rich in essential oils and various other
      significant phytoconstituents. Rapid direct regeneration was obtained from the
      rhizome explants (15.66 +/- 0.57 shoots) on MS media supplemented with zeatin at
      a concentration of 2 mg/l. The callus cultures of A. galanga were initiated from
      the rhizome explants on MS media supplemented with 2 mg/l each of BAP, 2,4-D, and
      NAA. The callus was analyzed for the presence of a vital phytoconstituent-
      acetoxychavicol acetate (ACA) associated with various biological properties. ACA
      was detected in the young friable callus as well as the stationary phase callus.
      Moreover, the induction of morphogenetic response in callus resulted in higher
      accumulation of ACA. The phytohormone withdrawal from the propagation media and
      the subsequent transfer of callus to BAP (2 mg/l) containing MS media has
      resulted in multiple shoot induction. The regenerated (indirect) plants have
      shown 1.6-fold higher ACA content (1.253%) when compared to the control plant
      (0.783%). Micropropagation of such conventionally propagated plants is very
      essential to meet the commercial demand as well as to ensure easy storage and
      transportation of disease free stocks.

PMID- 21892667
TI  - Enzymatic treatment and detoxification of acid orange 7 from textile wastewater.
AB  - A crude preparation of horseradish roots was used as a low-purity source of
      horseradish peroxidase (HRP) in dye decolorization experiments. The technical
      feasibility of the process was studied in bench scale for enzymatic removal of
      acid orange 7 (AO7), a synthetic dye. Further studies were carried out to
      understand the effects of process parameters such as pH value, H(2)O(2) level,
      concentrations of the synthetic dye, and HRP during enzyme-mediated dye
      degradation. Experimental data revealed that the concentration of AO7, pH of the
      aqueous phase, amount of the enzyme, and H(2)O(2) level played significant roles
      on the overall enzymatic reaction. Polyethylene glycol, as an anti-inactivation
      of HRP, in various concentrations showed no significant effect on the
      decolorization. The experimental data of initial reaction rates were fitted using
      an analytical equation proposed by Michaelis-Menten. The acute toxicity tests
      using Daphnia magna exhibited that the enzymatic treatment significantly
      decreased the toxicity of the dye solution.

PMID- 21892668
TI  - Association between weight gain, obesity, and sleep duration: a large-scale 3
      year cohort study.
AB  - OBJECTIVE: Previous research suggests that sleep duration is associated with
      obesity and weight gain. However, the majority of these studies are of cross
      sectional design, with only a few cohort studies. In order to validate previous
      findings in a more real-world context, we evaluated the association between sleep
      duration, obesity, and weight gain in a large, 3-year cohort study. METHODS: A
      retrospective cohort study was conducted involving 21,469 apparently healthy
      individuals aged 20 years or older who underwent annual health check-ups at the
      Center for Preventive Medicine, St. Luke's International Hospital, between 2005
      and 2008. The participants were divided into four groups according to their self
      reported average nightly sleep duration (<=5, 6, 7, and >=8 h). We identified
      individuals with obesity (body mass index >=25 kg/m(2)) and weight gain.
      Multivariate linear regression analysis and logistic regression analysis were
      used to explore the association between these variables and sleep duration,
      adjusting for age, gender, alcohol consumption, current smoking, past medical
      history, and level of physical activity. RESULTS: Compared with those who slept 7
      h, the individuals who slept <=5 h night were more likely to experience weight
      gain (beta coefficient = 0.03; 95% CI = 0.03-1.1) and to become obese (OR = 1.5;
      95% CI = 1.1-2.0). No significant difference was seen between subjects who slept
      more than 8 h and those sleeping 7 h (OR = 1.3; 95% CI = 0.9-1.8). CONCLUSION:
      Short sleep (<=5 h) is significantly associated with weight gain and obesity in
      both male and female adults.

PMID- 21892669
TI  - Extraosseous Ewing's sarcoma of the pancreas.
AB  - The Ewing's family of tumors (EFT) comprises a molecularly defined group of
      "small round blue cell tumors", consisting of Ewing's sarcoma of bone (ESB),
      extraosseous Ewing's sarcoma (EES), peripheral primitive neuroectodermal tumor
      (pPNET), and Askin's tumor. Characteristic translocations that disrupt the EWSR1
      gene located at 22q12 create novel fusion genes that are central to the
      pathogenesis. The EFT also shares certain clinical characteristics, such as a
      peak incidence during the teenage years, a tendency to spread rapidly, and
      responsiveness to the same chemotherapeutic regimens and radiation therapy.
      Nearly all patients have occult disseminated disease at diagnosis; hence,
      chemotherapy is routinely used. Improvements in multimodality treatment have had
      a dramatic impact on outcomes. EES/pPNET has been reported in a variety of sites,
      including the pancreas, though this is extremely rare. We describe a case of
      pancreatic EES/pPNET in a 35-year-old woman and provide a brief review of the
      relevant literature.

PMID- 21892670
TI  - Thinking twice before abandoning first-line chemotherapy in ovarian cancer:
      report of two cases and literature review. Passing from tri-weekly to weekly
      regimens.
AB  - We present two cases of advanced ovarian cancer treated with neoadjuvant
      chemotherapy with standard tri-weekly carboplatin and paclitaxel. Therapy was
      converted to weekly regimens because of disease progression, resulting in disease
      response. Weekly regimens could overcome drug resistance and this strategy should
      be attempted before abandoning first-line chemotherapy in favor of palliation.

PMID- 21892671
TI  - Study protocol of a multicenter registry of patients with rheumatoid arthritis
      starting biologic therapy in Japan: Tsurumai Biologics Communication Registry
      (TBCR) study.
AB  - Biologic agents have proven to be effective against rheumatoid arthritis (RA) in
      clinical trials and post-marketing surveillance (PMS) studies. However, limited
      follow-up periods and strict criteria for recruitment might lead to an
      underestimation of adverse events. To document the long-term course of patients
      with RA treated with biologics in clinical settings, we established the Tsurumai
      Biologics Communication Registry (TBCR). First, we retrospectively collected data
      of patients registered for any biologic PMS study or clinical trial at
      participating institutes. Thus far, thirteen institutes have joined the registry
      and 860 patients have been identified. Comparing baseline characteristics by age
      and initiation year of biologics, young patients had significantly less joint
      damage and dysfunction and a higher dose of concomitant methotrexate (MTX)
      compared to older patients. Older age and functional class were significantly
      related to the incidence of adverse events that resulted in discontinuation of
      the 1st biologic treatment. The TBCR is in its initial stages, and information on
      all patients newly starting biologic therapy at participating institutes is being
      collected prospectively. Differences in baseline characteristics by age and
      initiation year of biologics need to be carefully evaluated in order to report on
      drug-related survival and long-term prognosis, using follow-up data in the near
      future.

PMID- 21892672
TI  - Independent origins of vectored plant pathogenic bacteria from arthropod
      associated Arsenophonus endosymbionts.
AB  - The genus Arsenophonus (Gammaproteobacteria) is comprised of intracellular
      symbiotic bacteria that are widespread across the arthropods. These bacteria can
      significantly influence the ecology and life history of their hosts. For
      instance, Arsenophonus nasoniae causes an excess of females in the progeny of
      parasitoid wasps by selectively killing the male embryos. Other Arsenophonus
      bacteria have been suspected to protect insect hosts from parasitoid wasps or to
      expand the host plant range of phytophagous sap-sucking insects. In addition, a
      few reports have also documented some Arsenophonus bacteria as plant pathogens.
      The adaptation to a plant pathogenic lifestyle seems to be promoted by the
      infection of sap-sucking insects in the family Cixiidae, which then transmit
      these bacteria to plants during the feeding process. In this study, we define the
      specific localization of an Arsenophonus bacterium pathogenic to sugar beet and
      strawberry plants within the plant hosts and the insect vector, Pentastiridius
      leporinus (Hemiptera: Cixiidae), using fluorescence in situ hybridization assays.
      Phylogenetic analysis on 16S rRNA and nucleotide coding sequences, using both
      maximum likelihood and Bayesian criteria, revealed that this bacterium is not a
      sister taxon to "Candidatus Phlomobacter fragariae," a previously characterized
      Arsenophonus bacterium pathogenic to strawberry plants in France and Japan.
      Ancestral state reconstruction analysis indicated that the adaptation to a plant
      pathogenic lifestyle likely evolved from an arthropod-associated lifestyle and
      showed that within the genus Arsenophonus, the plant pathogenic lifestyle arose
      independently at least twice. We also propose a novel Candidatus status,
      "Candidatus Arsenophonus phytopathogenicus" novel species, for the bacterium
      associated with sugar beet and strawberry diseases and transmitted by the
      planthopper P. leporinus.

PMID- 21892673
TI  - [The role of resilience for coping in different age groups].
AB  - Personality traits, e.g., resilience, which is defined as emotional strength,
      have a strong impact on lifespan development. In this paper, a cross-sectional
      study examining the protective character of resilience in aging is presented. In
      a sample of persons ranging in age from 30-80 years, a significant negative
      association between resilience and depression was observed for the oldest group
      of our sample (age > 70 years). Thus, resilience might serve as a "safe-guard"
      against depression over the life course that, however, was found to disappear
      when people are faced with a transition into dependency and being in need of
      care.

PMID- 21892674
TI  - [Zones of transition: dimensions and interpretative patterns of aging].

PMID- 21892675
TI  - The cost of fall related presentations to the ED: a prospective, in-person,
      patient-tracking analysis of health resource utilization.
AB  - We prospectively collected data on elderly fallers to estimate the total cost of
      a fall requiring an Emergency Department presentation. Using data collected on
      102 falls, we found the average cost per fall causing an Emergency Department
      presentation of $11,408. When hospitalization was required, the average cost per
      fall was $29,363. INTRODUCTION: For elderly persons, falls are a major source of
      mortality, morbidity, and disability. Previous Canadian cost estimates of
      seniors' falls were based upon administrative data that has been shown to
      underestimate the incidence of falls. Our objective was to use a labor-intensive,
      direct observation patient-tracking method to accurately estimate the total cost
      of falls among seniors who presented to a major urban Emergency Department (ED)
      in Canada. METHODS: We prospectively collected data from seniors (>70 years)
      presenting to the Vancouver General Hospital ED after a fall. We excluded
      individuals who where cognitively impaired or unable to read/write English. Data
      were collected on the care provided including physician
      assessments/consultations, radiology and laboratory tests, ED/hospital time,
      rehabilitation facility time, and in-hospital procedures. Unit costs of health
      resources were taken from a fully allocated hospital cost model. RESULTS: Data
      were collected on 101 fall-related ED presentations. The most common diagnoses
      were fractures (n = 33) and lacerations (n = 11). The mean cost of a fall causing
      ED presentation was $11,408 (SD: $19,655). Thirty-eight fallers had injuries
      requiring hospital admission with an average total cost of $29,363 (SD: $22,661).
      Hip fractures cost $39,507 (SD: $17,932). Among the 62 individuals not admitted
      to the hospital, the average cost of their ED visit was $674 (SD: $429).
      CONCLUSIONS: Among the growing population of Canadian seniors, falls have
      substantial costs. With the cost of a fall-related hospitalization approaching
      $30,000, there is an increased need for fall prevention programs.

PMID- 21892676
TI  - Effect of supervised and home exercise training on bone mineral density among
      breast cancer patients. A 12-month randomised controlled trial.
AB  - The ability of combined step aerobic- and circuit-training to prevent bone loss
      after breast cancer treatments was related to skeletal site and patients'
      menopausal status. Among premenopausal breast cancer survivors, a 12-month
      exercise intervention completely prevented bone loss at the femoral neck, whereas
      no exercise effect was seen at lumbar spine or at neither site in postmenopausal
      women. INTRODUCTION: The primary objective of this randomised clinical trial was
      to determine the preventive effect of supervised weight-bearing jumping exercises
      and circuit training on bone loss among breast cancer patients. METHODS: Of 573
      breast cancer survivors aged 35-68 years randomly allocated into exercise or
      control group after adjuvant treatments, 498 (87%) were included in the final
      analysis. The 12-month exercise intervention comprised weekly supervised step
      aerobic- and circuit-exercises and similar home training. Bone mineral density
      (BMD) at lumbar spine and femoral neck were measured by dual-energy X-ray
      absorptiometry. Physical performance was assessed by 2-km walking and figure-8
      running tests, and the amount of physical activity was estimated in metabolic
      equivalent-hours/week. RESULTS: In premenopausal women, bone loss at the femoral
      neck was prevented by exercise, the mean BMD changes being -0.2% among the
      trainees vs. -1.4% among the controls (p = 0.01). Lumbar bone loss could not be
      prevented (-1.9% vs. -2.2%). In postmenopausal women, no significant exercise
      effect on BMD was found either at the lumbar spine (-1.6% vs. -2.1%) or femoral
      neck (-1.1% vs. -1.1%). CONCLUSIONS: This 12-month aerobic jumping and circuit
      training intervention completely prevented femoral neck bone loss in
      premenopausal breast cancer patients, whereas no effect on BMD was seen in
      postmenopausal women.

PMID- 21892677
TI  - Infections in postmenopausal women with osteoporosis treated with denosumab or
      placebo: coincidence or causal association?
AB  - Serious adverse events of infections that occurred in subjects receiving
      denosumab or placebo in the Fracture Reduction Evaluation of Denosumab in
      Osteoporosis every 6 Months (FREEDOM) study were examined in detail. Serious
      adverse events of infections in denosumab subjects had heterogeneous etiology,
      with no clear clinical pattern to suggest a relationship to time or duration of
      exposure to denosumab. INTRODUCTION: Denosumab reduces the risk for new
      vertebral, hip, and nonvertebral fractures compared with placebo. In the pivotal
      phase 3 fracture trial (FREEDOM), the overall safety profile and incidence of
      adverse events including adverse events of infections were similar between
      groups. Serious adverse events of erysipelas and cellulitis were more frequent in
      denosumab-treated subjects. In this report, we further evaluate the details of
      infectious events in FREEDOM to better understand if RANKL inhibition with
      denosumab influences infection risk. METHODS: FREEDOM was an international
      multicenter, randomized, double-blind, placebo-controlled study in postmenopausal
      women with osteoporosis randomly assigned to receive placebo (n = 3,906) or
      denosumab 60 mg every 6 months (n = 3,902). The incidence of adverse events and
      serious adverse events categorized within the Medical Dictionary for Regulatory
      Activities system organ class, "Infections and Infestations," was compared
      between the placebo and denosumab groups by body systems and preferred terms. The
      temporal relationship between occurrence of serious adverse events of infections
      of interest and administration of denosumab was explored. RESULTS: Serious
      adverse events of infections involving the gastrointestinal system, renal and
      urinary system, ear, and endocarditis were numerically higher in the denosumab
      group compared with placebo, but the number of events was small. No relationship
      was observed between serious adverse events of infections and timing of
      administration or duration of exposure to denosumab. CONCLUSIONS: Serious adverse
      events of infections that occurred with denosumab treatment had heterogeneous
      etiology, with no clear clinical pattern to suggest a relationship to time or
      duration of exposure to denosumab.

PMID- 21892678
TI  - The effects of combined human parathyroid hormone (1-34) and zoledronic acid
      treatment on fracture healing in osteoporotic rats.
AB  - Ovariectomized (OVX) rats with tibial fracture received vehicle, ZA, PTH, or ZA
      plus PTH treatment for 4 and 8 weeks. Bone metabolism, callus formation, and the
      mass of undisturbed bone tissue were evaluated by serum analysis, histology,
      immunohistochemistry, radiography, micro-computerized tomography, and
      biomechanical test. INTRODUCTION: Previous studies have demonstrated the effect
      of ZA or PTH on osteoporotic fracture healing. However, reports about effects of
      ZA plus PTH on callus formation of osteoporotic fracture were limited. This study
      was designed to investigate the impact of combined treatment with ZA and PTH on
      fracture healing in OVX rats. METHODS: Twelve weeks after bilateral ovariectomy,
      all rats underwent unilateral transverse osteotomy on tibiae. Animals then
      randomly received vehicle, ZA (1.5 MUg/kg weekly), PTH (60 MUg/kg, three times a
      week), or ZA plus PTH until death at 4 and 8 weeks. The blood and bilateral
      tibiae of rats were harvested for evaluation. RESULTS: All treatments increased
      callus formation and strength other than the control; ZA + PTH showed the
      strongest effects on percent bone volume (BV/TV), trabecular thickness, total
      fluorescence-marked callus area, and biomechanical strength. Additionally,
      inhibited RANKL and enhanced osteoprotegerin expression were observed in the ZA +
      PTH group. But no difference in bone mineral density and BV/TV of the
      contralateral tibiae was observed between treated groups. CONCLUSION: Findings in
      this study suggested an additive effect of ZA and PTH on fracture healing in OVX
      rats, and this additive effect was specific to callus formation, not to
      undisturbed bone tissue.

PMID- 21892683
TI  - Permanent suture used in uterosacral ligament suspension offers better anatomical
      support than delayed absorbable suture.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study was to compare the
      outcomes of uterosacral ligament suspension (USLS) procedures in relation to
      suture material used for apical suspension. METHODS: A retrospective chart review
      was performed for two senior surgeons who supervised and performed USLS with both
      suture types in 2008-2009. Permanent and delayed absorbable sutures were compared
      for failure of anatomical support. Failure, defined as recurrent prolapse beyond
      the hymen, was evaluated using survival analysis. RESULTS: Two hundred forty
      eight procedures were performed. One percent in the permanent group had a loss of
      support beyond the hymen compared to 6% in the delayed absorbable group (p =
      0.034). The preoperative prolapse stage and duration of follow-up did not differ
      between the two groups. The number of sutures used did not differ between
      patients who failed and those who did not fail. CONCLUSIONS: The use of permanent
      sutures for USLS of the vaginal apex was associated with a lower failure rate
      than delayed absorbable sutures in the short-term.

PMID- 21892685
TI  - Highlights of IUGA 36th Annual Meeting in Lisbon 2011.

PMID- 21892684
TI  - Retrospective study on tension-free vaginal tape obturator (TVT-O).
AB  - INTRODUCTION AND HYPOTHESIS: We aim to report the 3-year outcome and
      complications of the tension-free vaginal tape obturator (TVT-O) in treating
      female stress urinary incontinence (SUI). METHODS: Retrospective analysis for
      complications and outcome of surgery was performed in 419 women undergoing the
      TVT-O from 2004 to 2006. RESULTS: Three patients (0.8%) with an isolated TVT-O
      had a blood loss of more than 200 ml. Two patients (0.5%) had bladder
      perforation. Out of 11 readmitted patients (2.6%), 10 were due to voiding
      difficulty. Six patients (1.4%) required tape loosening or division. Persistent
      pain occurred in 3.6% and erosion in 2.4% of patients. One hundred eighty-five
      patients (44.2%) came for follow-up at 3 years. The actual subjective and
      objective success rates were 89.7% and 99.9% at 3 years follow-up, respectively.
      With imputation, the 3-year subjective and objective success rates were 86.9% and
      97.4%, respectively. CONCLUSIONS: The TVT-O is effective in treating female SUI
      with minimal complications.

PMID- 21892686
TI  - Seasonal influences on population spread and persistence in streams: spreading
      speeds.
AB  - The drift paradox asks how stream-dwelling organisms can persist, without being
      washed out, when they are continuously subject to the unidirectional stream flow.
      To date, mathematical analyses of the stream paradox have investigated the
      interplay of growth, drift and flow needed for species persistence under the
      assumption that the stream environment is temporally constant. However, in
      reality, streams are subject to major seasonal variations in environmental
      factors that govern population growth and dispersal. We consider the influence of
      such seasonal variations on the drift paradox, using a time-periodic
      integrodifferential equation model. We establish upstream and downstream
      spreading speeds under the assumption of periodically fluctuating environments,
      and also show the existence of periodic traveling waves. The sign of the upstream
      spreading speed then determines persistence. Fluctuating environments are
      characterized by seasonal correlations between the flow, transfer rates,
      diffusion and settling rates, and we investigate the effect of such correlations
      on the population spread and persistence. We also show how results in this paper
      can formally connect to those for autonomous integrodifferential equations,
      through the appropriate weighted averaging methods. Finally, for a specific
      dispersal function, we show that the upstream spreading speed is nonnegative if
      and only if the critical domain size exists in this temporally fluctuating
      environment.

PMID- 21892687
TI  - Glucagon-like peptide-1 (GLP-1) receptor agonists, obesity and psoriasis:
      diabetes meets dermatology.
AB  - Type 2 diabetes mellitus is characterised by beta cell failure, which frequently
      develops in the setting of insulin resistance. Inflammation contributes to the
      pathophysiology of type 2 diabetes by impairing insulin action in peripheral
      tissues and via reduction of beta cell function. Inflammation may also play an
      important role in the development of complications that arise in patients with
      type 2 diabetes. Hence, the anti-inflammatory actions of commonly used glucose
      lowering drugs may contribute, indirectly, to their mechanisms of action and
      therapeutic benefit. Herein we highlight the anti-inflammatory actions of
      glucagon-like peptide-1 (GLP-1), which exerts direct and indirect actions on
      immune function. The observations that GLP-1 receptor agonists exert anti
      inflammatory actions in preclinical studies, taken together with case reports
      linking improvements in psoriasis with GLP-1 receptor agonist therapy,
      illustrates the emerging clinical implications of non-classical anti-inflammatory
      actions of incretin-based therapeutics.

PMID- 21892688
TI  - The mechanism of hydrogen uptake in [NiFe] hydrogenase: first-principles
      molecular dynamics investigation of a model compound.
AB  - The recent discovery of a model compounds of [NiFe] hydrogenase that catalyzes
      the heterolytic cleavage of the H(2) molecule into a proton and a stable hydride
      in water solution under room conditions opened up the possibility to understand
      the mechanism of H(2) uptake by this peculiar class of enzymes. The simplest
      model compound belongs to the class of NiRu bimetallic cationic complexes
      mimicking, in water solution and at room conditions, the hydrogenase active site.
      By using first-principles molecular dynamics computer simulations, in the Car
      Parrinello scheme, we investigated models including the water solvent and nitrate
      counterions. Several simulations, starting from different initial configurations,
      provided information on the first step of the H(2) cleavage: (1) the pathway of
      H(2) approach towards the active site; (2) the role of the ruthenium-bonded water
      molecule in providing a base that extracts the proton from the activated H(2)
      molecule; (3) the minor role of Ni in activating the H(2) molecule and its role
      in stabilizing the hydride produced.

PMID- 21892689
TI  - Nitric oxide implicates c-Fos expression in the cuneate nucleus following
      electrical stimulation of the transected median nerve.
AB  - In this study, we investigated whether nitric oxide (NO) modulated injury-induced
      neuropeptide Y (NPY) releasing and c-Fos expression in the cuneate nucleus (CN)
      after median nerve transection (MNT). We first examined the temporal changes of
      neuronal nitric oxide synthase (nNOS) expression in the dorsal root ganglion
      (DRG) and CN after MNT. Following MNT, the amounts of nNOS-like immunoreactive
      (nNOS-LI) neurons in the DRG and CN significantly increased as compared with
      those of the sham-operated rats. Furthermore, 4 weeks after MNT, the increases of
      nNOS-LI neurons in the DRG and CN were attenuated by pre-emptive lidocaine
      treatment in a dose-dependent manner. Finally, 4 weeks after MNT, pre-stimulation
      administration of L-NAME (N (omega)-Nitro-L: -arginine methyl ester) or 7-NI (7
      nitroindazole) suppressed the amount of NPY release from the stimulated terminals
      and thus attenuated c-Fos expression in the CN. Our data implied that NO would
      modulate neuronal activity in the DRG and CN both after MNT.

PMID- 21892690
TI  - Inhibition of neuron-specific CREB dephosphorylation is involved in propofol and
      ketamine-induced neuroprotection against cerebral ischemic injuries of mice.
AB  - Propofol and ketamine may provide certain degree of neuroprotection, but the
      underlying mechanism remains unclear to date. The cAMP response element-binding
      protein (CREB) was proposed that its phosphorylation at Ser133 (P-CREB)
      constituted a convergence point involved in neuroprotection. The purpose of this
      study was to determine whether different dosages of propofol and ketamine could
      provide neuroprotection against permanent middle cerebral artery occlusion (MCAO)
      induced ischemic injuries and the involvement of P-CREB. Eighty adult male BALB/c
      mice that underwent 6 h MCAO were randomly divided into eight groups: Sham
      operation; MCAO + saline; MCAO + 25, 50, 100 mg/kg propofol; and MCAO + 25, 50,
      100 mg/kg ketamine (intraperitoneal injection 30 min following MCAO). We found
      that 50, 100 (not 25) mg/kg propofol, and 25 (not 50 and 100) mg/kg ketamine
      could significantly reduce the infarct volume, edema ratio and neurological
      deficit (n = 10 per group) as well as inhibit the decrease of P-CREB level in
      peri-infarct region when compared with that of MCAO + saline group (n = 6 per
      group). In addition, the results of double-labeled immunofluorescent staining
      showed that P-CREB co-localized with neuron-specific marker, NeuN, in the peri
      infarct region of 50 mg/kg propofol and 25 mg/kg ketamine treated 6 h MCAO mice
      (n = 4 per group). These results suggested that inhibition of neuron-specific P
      CREB dephosphorylation in the peri-infarct region is involved in high dose
      propofol and low dose ketamine-induced neuroprotection of 6 h MCAO mice.

PMID- 21892691
TI  - Women bar drinkers' discussions about birth control and risky sexual behavior.
AB  - This study evaluated how birth control discussions prior to sexual activity
      affected condom use in a sample of 225 young women bar drinkers. The use of
      alcohol and other drugs (AOD) and partner type also were assessed. Data were
      collected through daily reports and qualitative interviews over 12 weeks. A total
      of 1671 sexual events were reported (M = 7.4 events per participant), of which
      64.7% (n = 1081) did not involve condom use. Discussions of birth control
      occurred prior to 10.9% (n = 183) of all sexual events. These discussions were
      more likely to be initiated by the woman and to occur when AOD had been used.
      Thematic analysis revealed four common themes: confirmation of the need to use
      condoms, confirmation of oral/hormonal contraceptive use, use of sufficient birth
      control, and discrepant condom use. The discussions reduced rates of risky sex
      when the sexual partner was more intimate (i.e., boyfriend/dating partner),
      regardless of AOD use and when the sexual partner was a friend or ex-partner and
      no AOD were used. The thematic analysis suggested that pregnancy prevention was a
      stronger motivation for discussing condom use, rather than risk of contracting an
      STI. Given the substantial rate of high risk partners, history of STIs, and
      limited amount of time women reported knowing "regular" partners, we suggest that
      interventions designed to reduce risky sex should be tailored to increase women's
      awareness of STI and pregnancy risk when under the influence of AOD, and promote
      condom use regardless of partner type.

PMID- 21892692
TI  - Attributions for discriminatory events and satisfaction with social support in
      gay men.
AB  - Attributions modulate the impact of stressful events on mental health. However,
      little is known about attributions for discriminatory events and their
      relationship to psychosocial outcomes in sexual minority individuals.
      Relationships were examined between gay men's attributions for discrimination and
      their satisfaction with social support, a variable critical to mental health in
      this population. Gay men (N=307) completed online measures of satisfaction with
      social support, attributions for discriminatory events, and key minority stress
      constructs. Self blaming attributions for discrimination were associated with
      decreased satisfaction with social support, independent of the frequency with
      which participants reported experiencing discrimination. The link between self
      blaming and satisfaction with social support was partially mediated by a latent
      affective construct comprised of anxiety, depression, and low positive affect. A
      moderation effect was also found, such that the relationship between frequency of
      perceived discriminatory events and dissatisfaction with social support was
      amplified for men reporting more blame toward perpetrators of discrimination.
      Results support attributions for discrimination as valuable additions to minority
      stress models. Assessing self and other blame for these discriminatory events may
      help to clarify pathways by which discrimination can undermine gay men's
      satisfaction with their social support networks.

PMID- 21892693
TI  - Attentional and affective processing of sexual stimuli in women with hypoactive
      sexual desire disorder.
AB  - Hypoactive sexual desire disorder (HSDD) is the most common sexual problem in
      women. From an incentive motivation perspective, HSDD may be the result of a weak
      association between sexual stimuli and rewarding experiences. As a consequence,
      these stimuli may either lose or fail to acquire a positive meaning, resulting in
      a limited number of incentives that have the capacity to elicit a sexual
      response. According to current information processing models of sexual arousal,
      sexual stimuli automatically activate meanings and if these are not predominantly
      positive, processes relevant to the activation of sexual arousal and desire may
      be interrupted. Premenopausal U.S. and Dutch women with acquired HSDD (n = 42)
      and a control group of sexually functional women (n = 42) completed a single
      target Implicit Association Task and a Picture Association Task assessing
      automatic affective associations with sexual stimuli and a dot detection task
      measuring attentional capture by sexual stimuli. Results showed that women with
      acquired HSDD displayed less positive (but not more negative) automatic
      associations with sexual stimuli than sexually functional women. The same pattern
      was found for self-reported affective sex-related associations. Participants were
      slower to detect targets in the dot detection task that replaced sexual images,
      irrespective of sexual function status. As such, the findings point to the
      relevance of affective processing of sexual stimuli in women with HSDD, and imply
      that the treatment of HSDD might benefit from a stronger emphasis on the
      strengthening of the association between sexual stimuli and positive meaning and
      sexual reward.

PMID- 21892694
TI  - Azathioprine induced hepatitis in patients with inflammatory bowel disease.

PMID- 21892695
TI  - Nitrendipine nanocrystals: its preparation, characterization, and in vitro-in
      vivo evaluation.
AB  - The present investigation was undertaken with the objective of developing a solid
      formulation containing nitrendipine nanocrystals for oral delivery. Nitrendipine
      nanocrystals were prepared using a tandem precipitation-homogenization process.
      Then, spray drying, a cost-effective method very popular in industrial
      situations, was employed to convert the nanocrystals into a solid form. The
      parameters of the preparation process were investigated and optimized. The
      optimal process was as follows: firstly, nitrendipine/acetone solution (100
      mg/ml) was added to a polyvinyl alcohol solution (1 mg/ml) at 10 degrees C, then
      the pre-suspension was homogenized for 20 cycles at 1,000 bar. Both differential
      scanning calorimetry and X-ray diffraction analysis indicated that nitrendipine
      was present in crystalline form. The in vitro dissolution rate of the
      nanocrystals was significantly increased compared with the physical mixture and
      commercial tablet. The in vivo testing demonstrated that the C(max) of the
      nanocrystals was approximately 15-fold and 10-fold greater than that of physical
      mixture and commercial tablet, respectively. In addition, the AUC(0->24) of the
      nanocrystals was approximately 41-fold and 10-fold greater than that of physical
      mixture and commercial tablet, respectively.

PMID- 21892696
TI  - Treatment outcome and risk factors for visual loss in Cytomegalovirus
      endotheliitis.
AB  - BACKGROUND: To determine treatment outcome and risk factors for visual loss in
      Cytomegalovirus (CMV) endotheliitis. METHODS: Retrospective case-note review of
      all CMV positive endotheliitis patients seen at the Singapore National Eye
      Center, for demographics, visual acuity (VA), extent of corneal edema, anterior
      chamber (AC) activity, ocular history, glaucomatous optic neuropathy (GON), and
      ganciclovir therapy. Outcome measures were VA, corneal edema, and AC activity.
      RESULTS: Median age at diagnosis of the 19 patients (21 eyes) was 57 years.
      Median duration of follow up was 37 months. Sixteen eyes received systemic
      ganciclovir, and four eyes received ganciclovir gel. The AC inflammation resolved
      in 19 eyes. The corneal edema resolved in eight eyes, but persisted in 12 eyes.
      One patient resolved spontaneously. Pre-treatment corneal edema exceeding 75%,
      older age, GON, and previous corneal graft were risk factors for persistent
      corneal edema post treatment (P = < 0.001, 0.001, 0.02 and 0.02 respectively,
      Fisher's exact test), and VA worse than 6/60. CONCLUSIONS: Anterior chamber
      inflammation resolves with ganciclovir therapy, but severe pre-treatment corneal
      edema, older age, previous corneal graft, and GON are associated with a poor
      visual outcome.

PMID- 21892697
TI  - Radiographic findings in late-presenting congenital diaphragmatic hernia: helpful
      imaging findings.
AB  - BACKGROUND: Imaging findings in delayed presentation of congenital diaphragmatic
      hernia can be confusing and misleading, resulting in a delay in diagnosis.
      OBJECTIVE: To evaluate the often puzzling plain film findings of late-presenting
      CDH in an effort to determine whether any of the findings could be helpful in
      arriving at an early diagnosis. MATERIAL AND METHODS: We reviewed and documented
      the plain film findings and clinical data in eight patients seen during the last
      20 years with late-presenting CDH. IRB exempt status was obtained in this study.
      RESULTS: There were five boys and three girls. The age range was 4 months to 12
      years with a mean of 2.4 years. Five children presented with acute respiratory
      problems while three presented with acute abdominal pain. Two children presented
      with both respiratory and abdominal findings and one also presented with
      hematemesis. Two children had radiographic findings that were not difficult to
      analyze while the remaining six had findings that posed initial diagnostic
      problems. CONCLUSION: Although not common, late-presenting CDH can result in
      confusing plain film radiographic findings and a delay in diagnosis. We found
      that the most important finding in analyzing these radiographs is in evaluating
      the location and position of the gastric bubble with the more common left-side
      hernias.

PMID- 21892698
TI  - Adipocytes Promote B16BL6 Melanoma Cell Invasion and the Epithelial-to
      Mesenchymal Transition.
AB  - Metastatic melanoma is one of the most deadly and evasive types of cancer. On
      average, cancer patients with metastatic melanoma survive only 6-9 months after
      diagnosis. Epidemiological and animal studies suggest that obesity increases the
      metastatic ability of malignant melanoma, though the mechanism is not known. In
      the present studies, we assessed the ability of 3T3L1 adipocytes to modulate
      B16BL6 melanoma cell invasion and the Epithelial-to-Mesenchymal Transition (EMT).
      For this purpose, we induced the differentiation of 3T3L1 fibroblasts to
      adipocytes. Then, we collected the cell culture media from both fibroblasts and
      adipocytes and determined their effect on the invasive ability and EMT gene
      expression of B16BL6 melanoma cells. Results show that adipocyte media increased
      that ability of B16BL6 cells to invade. The higher invasive ability of B16BL6
      melanoma cells was associated with increased expression of EMT genes such as
      Snai1, MMP9, Twist, and Vimentin. Additionally, the expression of the cell-to
      cell adhesion protein E-cadherin and the metastasis suppressor gene Kiss1 were
      down-regulated in these B16BL6 cells. Also, adipocytes had high levels of the pro
      inflammatory cytokine Interleukin 6 (IL-6). Treatment of B16BL6 cells with IL-6
      elicited similar effects as the adipocyte media; IL-6 promoted the invasive
      ability of B16BL6 melanoma cells, increased the expression of Snai1, and
      decreased Kiss1 expression. IL-6 neutralization, however, did not have a visible
      effect on adipocyte media-induced invasion and snai1 staining. In summary,
      adipocytes may increase the invasive ability of B16BL6 melanoma cells by
      promoting EMT and decreasing the expression of genes such as E-cadherin and
      Kiss1.

PMID- 21892699
TI  - Partial mesenchymal to epithelial reverting transition in breast and prostate
      cancer metastases.
AB  - Epithelial to mesenchymal transition (EMT) is an oft-studied mechanism for the
      initiation of metastasis. We have recently shown that once cancer cells
      disseminate to a secondary organ, a mesenchymal to epithelial reverting
      transition (MErT) may occur, which we postulate is to enable metastatic
      colonization. Despite a wealth of in vitro and in vivo studies, evidence
      supportive of MErT in human specimens is rare and difficult to document because
      clinically detectable metastases are typically past the micrometastatic stage at
      which this transition is most likely evident. We obtained paired primary and
      metastatic tumors from breast and prostate cancer patients and evaluated
      expression of various epithelial and mesenchymal markers by immunohistochemistry.
      The metastases exhibited increased expression of membranous E-cadherin compared
      to primary tumors, consistent with EMT at the primary site and MErT at the
      metastatic site. However, the re-emergence of the epithelial phenotype was only
      partial or incomplete. Expression of epithelial markers connexins 26 and/or 43
      was also increased on the majority of metastases, particularly those to the
      brain. Despite the upregulation of epithelial markers in metastases, expression
      of mesenchymal markers vimentin and FSP1 was mostly unchanged. We also examined
      prostate carcinoma metastases of varied sizes and found that while E-cadherin
      expression was increased compared to the primary lesion, the expression inversely
      correlated with size of the metastasis. This not only suggests that a second EMT
      may occur in the ectopic site for tumor growth or to seed further metastases, but
      also provides a basis for the failure to discern epithelial phenotypes in
      clinically examined macrometastases. In summary, we report increased expression
      of epithelial markers and persistence of mesenchymal markers consistent with a
      partial MErT that readily allows for a second EMT at the metastatic site. Our
      results suggest that cancer cells continue to display phenotypic plasticity
      beyond the EMT that initiates metastasis.

PMID- 21892701
TI  - Using modified incremental chart parsing to ascribe intentions to animated
      geometric figures.
AB  - People spontaneously ascribe intentions on the basis of observed behavior, and
      research shows that they do this even with simple geometric figures moving in a
      plane. The latter fact suggests that 2-D animations isolate critical information-
      object movement--that people use to infer the possible intentions (if any)
      underlying observed behavior. This article describes an approach to using motion
      information to model the ascription of intentions to simple figures. Incremental
      chart parsing is a technique developed in natural-language processing that builds
      up an understanding as text comes in one word at a time. We modified this
      technique to develop a system that uses spatiotemporal constraints about simple
      figures and their observed movements in order to propose candidate intentions or
      nonagentive causes. Candidates are identified via partial parses using a library
      of rules, and confidence scores are assigned so that candidates can be ranked. As
      observations come in, the system revises its candidates and updates the
      confidence scores. We describe a pilot study demonstrating that people generally
      perceive a simple animation in a manner consistent with the model.

PMID- 21892700
TI  - An fMRI investigation of cerebellar function during verbal working memory in
      methadone maintenance patients.
AB  - Working memory is impaired in opioid-dependent individuals, yet the neural
      underpinnings of working memory in this population are largely unknown. Previous
      studies in healthy adults have demonstrated that working memory is supported by a
      network of brain regions that includes a cerebro-cerebellar circuit. The
      cerebellum, in particular, may be important for inner speech mechanisms that
      assist verbal working memory. This study used functional magnetic resonance
      imaging to examine brain activity associated with working memory in five opioid
      dependent, methadone-maintained patients and five matched, healthy controls. An
      item recognition task was administered in two conditions: (1) a low working
      memory load "match" condition in which participants determined whether target
      letters presented at the beginning of the trial matched a probe item, and (2) a
      high working memory load "manipulation" condition in which participants counted
      two alphabetical letters forward of each of the targets and determined whether
      either of these new items matched a probe item. Response times and accuracy
      scores were not significantly different between the groups. FMRI analyses
      indicated that, in association with higher working memory load ("manipulation"
      condition), the patient group exhibited hyperactivity in the superior and
      inferior cerebellum and amygdala relative to that of controls. At a more liberal
      statistical threshold, patients exhibited hypoactivity in the left prefrontal and
      medial frontal/pre-SMA regions. These results indicate that verbal working memory
      in opioid-dependent individuals involves a disrupted cerebro-cerebellar circuit
      and shed light on the neuroanatomical basis of working memory impairments in this
      population.

PMID- 21892702
TI  - Impact of mammographic screening on the detection of good and poor prognosis
      breast cancers.
AB  - We sought to compare the molecular signature of node negative cancers from two
      cohorts 15 years apart, to determine if there is molecular evidence of increase
      in low and ultralow risk cancers over time. We studied the impact of age, time
      period of diagnosis, and mammographic screening on biology of tumors where The
      Netherlands Cancer Institute 70-gene prognosis signature was generated as part of
      2 validation series, one retrospective (1984-1992), Cohort 1, and one prospective
      (2004-2006), Cohort 2. A total of 866 patients were analyzed. Regardless of time
      period of diagnosis, the proportion of T1, grade 1, hormone receptor positive
      (HR) tumors, and good prognosis by 70-gene signature significantly increases as
      age increases (P < 0.01). In women aged 49-60, the time period of diagnosis
      significantly affects the proportion of cancers that were NKI 70-gene low risk:
      40.6% (67/165) compared with 58% (119/205) for Cohorts 1 and 2, respectively.
      This is in contrast to the absence of a significant change for women under age
      40, where 25% (17/68) and 30% (17/56) were low risk in Cohorts 1 and 2,
      respectively. In women aged 49-60, using an ultralow risk threshold of the 70
      gene signature, 10% of tumors in Cohort 1 were ultralow risk compared with 30%
      for women with screen-detected cancers in Cohort 2. Older age and method of
      detection (screening) are associated with a higher likelihood of a biologically
      low risk tumor. In women over age 50, biologically low risk tumors are frequent
      and tools that classify risk may minimize overtreatment.

PMID- 21892703
TI  - Body mass index and risk of second primary breast cancer: the WECARE Study.
AB  - The identification of potentially modifiable risk factors, such as body size,
      could allow for interventions that could help reduce the burden of contralateral
      breast cancer (CBC) among breast cancer survivors. Studies examining the
      relationship between body mass index (BMI) and CBC have yielded mixed results.
      From the population-based, case-control, Women's Environmental, Cancer and
      Radiation Epidemiology (WECARE) Study, we included 511 women with CBC (cases) and
      999 women with unilateral breast cancer (controls) who had never used
      postmenopausal hormone therapy. Rate ratios (RR) and 95% confidence intervals
      (CI) were used to assess the relationship between BMI and CBC risk. No
      associations between BMI at first diagnosis or weight-change between first
      diagnosis and date of CBC diagnosis (or corresponding date in matched controls)
      and CBC risk were seen. However, obese (BMI >= 30 kg/m(2)) postmenopausal women
      with estrogen receptor (ER)-negative first primary tumors (n = 12 cases and 9
      controls) were at an increased risk of CBC compared with normal weight women (BMI
      < 25 kg/m(2)) (n = 43 cases and 98 controls) (RR = 5.64 (95% CI 1.76, 18.1)). No
      association between BMI and CBC risk was seen in premenopausal or postmenopausal
      women with ER-positive first primaries. Overall, BMI is not associated with CBC
      risk in this population of young breast cancer survivors. Our finding of an over
      five-fold higher risk of CBC in a small subgroup of obese postmenopausal women
      with an ER-negative first primary breast cancer is based on limited numbers and
      requires confirmation in a larger study.

PMID- 21892706
TI  - Transition to the clinical doctorate: attitudes of the genetic counseling
      training program directors in North America.
AB  - In North America, genetic counseling is an allied health profession where entry
      level practitioners currently must hold a master's degree earned from a graduate
      program accredited by the American Board of Genetic Counseling. This is one of
      many health care professions that could transition to an entry level clinical
      doctorate degree. This study explored the attitudes of genetic counseling
      training program directors toward such a transition. Thirty-one North American
      program directors were invited to complete an online survey and a follow-up
      telephone interview. Twenty-one program directors completed the survey and ten
      directors also completed a follow up phone interview. There was disagreement
      among the respondents on the issue of transitioning to a clinical doctorate
      degree (nine in favor, six against and six undecided). Respondents disagreed
      about whether the transition would lead to higher salaries (six yes, eight no,
      and seven unsure) or increased professional recognition (eight yes, eight no, and
      four unsure). Approximately half (n = 10) of directors were not sure if the
      transition to a clinical doctorate would help or hurt minority recruitment; six
      thought it would help and four thought it would hurt. However, the majority (n =
      13) thought a clinical doctorate would help genetic counselors to obtain faculty
      positions. If the field transitions to a clinical doctorate, 11 of the directors
      thought their program would convert, seven were unsure and one thought their
      program would shut down. Themes identified in interview data included 1)
      implications for the profession 2) institution-specific considerations and 3)
      perception of the unknown. Opinions are quite varied at this time regarding the
      possible transition to the clinical doctorate among genetic counseling training
      program directors.

PMID- 21892705
TI  - Urinary bladder cancer risk in relation to a single nucleotide polymorphism
      (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene.
AB  - Currently, twelve validated genetic variants have been identified that are
      associated with urinary bladder cancer (UBC) risk. However, those validated
      variants explain only 5-10% of the overall inherited risk. In addition, there are
      more than 100 published polymorphisms still awaiting validation or disproval. A
      particularly promising of the latter unconfirmed polymorphisms is rs2854744 that
      recently has been published to be associated with UBC risk. The [A] allele of
      rs2854744 has been reported to be associated with a higher promoter activity of
      the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to
      increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the
      association of rs2854744 with UBC in the IfADo case-control series consisting of
      1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No
      significant association of rs2854744 with UBC risk was obtained (all study groups
      combined: unadjusted P = 0.4446; adjusted for age, gender and smoking habits P =
      0.6510), besides a small effect of the [A] allele in the Pakistani study group
      opposed to the original findings (unadjusted P = 0.0508, odds ratio (OR) = 1.43
      for the multiplicative model) that diminished after adjustment for age, gender
      and smoking habits (P = 0.7871; OR = 0.93). Associations of rs2854744 with
      occupational exposure to urinary bladder carcinogens and smoking habits were also
      not present. A meta-analysis of all available case-control series including the
      original discovery study resulted in an OR of 1.00 (P = 0.9562). In conclusion,
      we could not confirm the recently published hypothesis that rs2854744 in the
      IGFBP3 gene is associated with UBC risk.

PMID- 21892707
TI  - The effects of PVP(Fe(III)) catalyst on polymer molecular weight and gene
      delivery via biodegradable cross-linked polyethylenimine.
AB  - PURPOSE: Crosslinked, degradable derivatives of low-molecular-weight
      polyethylenimine (PEI) are relatively efficient and non-cytotoxic gene delivery
      agents. To further investigate these promising materials, a new synthetic
      approach was developed using a poly(4-vinylpyridine)-supported Fe(III) catalyst
      (PVP(Fe(III))) that provides more facile synthesis and enhanced control of
      polymer molecular weight. METHODS: Biodegradable polymers (D.PEI) comprising 800
      Da PEI crosslinked with 1,6-hexanediol diacrylate and exhibiting molecular
      weights of 1.2, 6.2, and 48 kDa were synthesized utilizing the PVP(Fe(III))
      catalyst. D.PEI/DNA polyplexes were characterized using gel retardation, ethidium
      bromide exclusion, heparan sulfate displacement, and dynamic light scattering. In
      vitro transfection, cellular uptake, and cytotoxicity of the polyplexes were
      tested in human cervical cancer cells (HeLa) and human breast cancer cells (MDA
      MB-231). RESULTS: D.PEIs tightly complexed plasmid DNA and formed 320- to 440-nm
      diameter polyplexes, similar to those comprising non-degradable, 25-kDa, branched
      PEI. D.PEI polyplexes mediated 2- to 5-fold increased gene delivery efficacy
      compared to 25-kDa PEI and exhibited 20% lower cytotoxicity in HeLa and no
      toxicity in MDA-MB-231. In addition, 2- to 7-fold improved cellular uptake of DNA
      was achieved with D.PEI polyplexes. CONCLUSIONS: PVP(Fe(III)) catalyst provided a
      more controlled synthesis of D.PEIs, and these materials demonstrated improved in
      vitro transfection efficacy and reduced cytotoxicity .

PMID- 21892708
TI  - How well do selection tools predict performance later in a medical programme?
AB  - The choice of tools with which to select medical students is complex and
      controversial. This study aimed to identify the extent to which scores on each of
      three admission tools (Admission GPA, UMAT and structured interview) predicted
      the outcomes of the first major clinical year (Y4) of a 6 year medical programme.
      Data from three student cohorts (n = 324) were analysed using regression
      analyses. The Admission GPA was the best predictor of academic achievement in
      years 2 and 3 with regression coefficients (B) of 1.31 and 0.9 respectively (each
      P < 0.001). Furthermore, Admission GPA predicted whether or not a student was
      likely to earn 'Distinction' rather than 'Pass' in year 4. In comparison, UMAT
      and interview showed low predictive ability for any outcomes. Interview scores
      correlated negatively with those on the other tools. None of the tools predicted
      failure to complete year 4 on time, but only 3% of students fell into this
      category. Prior academic achievement remains the best measure of subsequent
      student achievement within a medical programme. Interview scores have little
      predictive value. Future directions include longer term studies of what UMAT
      predicts, and of novel ways to combine selection tools to achieve the optimum
      student cohort.

PMID- 21892709
TI  - Appropriateness: analysis of outpatient radiology requests.
AB  - PURPOSE: This study assessed radiology requests and the influence of previous
      radiological procedures on their specificity and appropriateness, evaluated
      diagnostic outcomes and recorded the economic impact of inappropriate
      examinations. MATERIALS AND METHODS: We prospectively analysed 4,018 outpatient
      requests, the appropriateness of which was assessed using an evaluation form.
      Economic analysis was based on costs listed in the Italian National Health
      Services (NHS) national tariff as established by the Ministerial Decree of 22
      July 1996. Statistical analysis was carried out using Pearson's test and
      univariate and multivariate logistic regression models. RESULTS: Of 4,018
      outpatient requests, 57% were not included in a follow-up protocol and 56% were
      found to be appropriate. The diagnostic question was confirmed in 66% of cases
      considered appropriate (p<0.001). The existence of previous investigations had a
      significant impact on appropriateness and diagnostic outcome (p<0.001). The total
      cost of the requests was 257,317 euro, with inappropriate requests accounting for
      94,012 euro (36.5%). CONCLUSIONS: We found a 56% rate of appropriate requests and
      demonstrated that appropriate prescriptions provided with a specific clinical
      question led to significantly higher confirmation rates of the diagnostic
      hypothesis. In addition, inappropriate requests had a major negative economic
      impact.

PMID- 21892710
TI  - Hypoxic liver perfusion with mitomycin-C for treating multifocal metastases and
      unresectable primary tumours: a single-centre series of 42 patients.
AB  - PURPOSE: The purpose of our study was to retrospectively evaluate the
      feasibility, toxicity and impact on overall (OS) and disease-free (DFS) survival
      of intra-arterial liver perfusion with mitomycin-C (MMC) [hypoxic liver perfusion
      with MMC (HLPM)] in patients with multifocal liver metastases or with
      unresectable primary liver tumours. MATERIALS AND METHODS: Forty-two patients
      underwent 56 intra-arterial liver infusions with MMC between June 2001 and May
      2009. The patients presented specific characteristics, i.e. they were all
      refractory to locoregional (LR) and/or systemic treatments. HLPM consists of
      selective catheterisation of the common hepatic artery, permanent occlusion of
      the gastroduodenal artery at its origin using metal coils, an inflated balloon
      catheter placement at the origin of the proper hepatic artery to block blood flow
      and induce hypoxia for around 10 min, MMC infusion and vascular-bed occlusion
      through injection of an absorbable haemostatic agent. During the procedure, the
      patients received anaesthesiological monitoring. Biochemical and morphological
      responses were evaluated, as were haematological, hepatic and systemic toxicity.
      RESULTS: Patients were hospitalised for 10 days on average (range 7-15). Side
      effects were liver toxicity in all cases, acute pancreatitis in one case and
      liver failure in one case. Computed tomography performed at 30 days documented a
      partial response (PR) in 29%, stable disease (SD) in 45% and progressive disease
      (PD) in 26% of patients. The response lasted 4 months on average (range 3-6).
      Mean overall survival (OS) was 20 months for all patients, reaching 30 months in
      those with colorectal carcinoma. CONCLUSIONS: The procedure is feasible, and
      treatmentrelated toxicity and mortality rates are acceptable. It may be
      considered a palliative treatment option in patients with advanced liver disease
      in centres with adequately experienced medical teams.

PMID- 21892711
TI  - Computed tomography coronary angiography in asymptomatic patients.
AB  - PURPOSE: This study assessed the accuracy of computed tomography coronary
      angiography (CT-CA) for detecting significant coronary artery disease (CAD; >=50%
      lumen reduction) in intermediate/high-risk asymptomatic patients. MATERIALS AND
      METHODS: A total of 183 consecutive asymptomatic individuals (92 men; mean age
      54+/-11 years) with more than one major risk factor (obesity, hypertension,
      diabetes, hypercholesterolaemia, family history, smoking) and an inconclusive or
      nonfeasible noninvasive stress test result (stress electrocardiography, stress
      echocardiography, nuclear stress scintigraphy) underwent CT-CA in an outpatient
      setting. All patients underwent conventional coronary angiography (CAG) within 4
      weeks. Data from CT-CA were compared with CAG regarding the presence of
      significant CAD (>=50% lumen reduction). RESULTS: Mean calcium score was 177+/
      432, mean heart rate during the CT-CA scan was 58+/-8 bpm and the prevalence (per
      patient) of obstructive CAD was 19%. CT-CA showed single-vessel CAD in 9% of
      patients, two-vessel CAD in 9% and three-vessel CAD in 0%. Per-patient
      sensitivity, specificity, positive predictive value and negative predictive value
      of CT-CA were 100% (90-100), 98% (96-99), 97% (85-99), 100% (97-100),
      respectively. Positive and negative likelihood ratios were 151 and 0,
      respectively. CONCLUSIONS: CT-CA is an excellent noninvasive imaging modality for
      excluding significant CAD in intermediate/ high-risk asymptomatic patients with
      inconclusive or nonfeasible noninvasive stress test.

PMID- 21892712
TI  - Coronary plaque burden in patients with stable and unstable coronary artery
      disease using multislice CT coronary angiography.
AB  - PURPOSE: We evaluated the multislice computed tomography (MSCT) coronary plaque
      burden in patients with stable and unstable angina pectoris. MATERIALS AND
      METHODS: Twenty-one patients with stable and 20 with unstable angina pectoris
      scheduled for conventional coronary angiography (CCA) underwent MSCT-CA using a
      64-slice scanner offering a fast rotation time (330 ms) and higher X-ray tube
      output (900 mAs). To determine the MSCT coronary plaque burden, we assessed the
      extent (number of diseased segments), size (small or large), type (calcific,
      noncalcific, mixed) of plaque, its anatomic distribution and angiographic
      appearance in all available >=2-mm segments. In a subset of 15 (seven stable,
      eight unstable) patients, the detection and classification of coronary plaques by
      MSCT was verified by intracoronary ultrasound (ICUS). RESULTS: Sensitivity and
      specificity of MSCT compared with ICUS to detect significant plaques (defined as
      >=1-mm plaque thickness on ICUS) was 83% and 87%. Overall, 473 segments were
      examined, resulting in 11.6+/-1.5 segments per patient. Plaques were present in
      62% of segments and classified as large in 47% of diseased segments. Thirty-two
      percent were noncalcific, 25% calcific and 43% mixed. Plaques were most
      frequently located in the proximal and mid segments. Plaque was found in 33% of
      segments classified as normal on CCA. Unstable patients had significantly more
      noncalcific plaques when compared with stable patients (45% vs. 21%, p<0.05).
      CONCLUSIONS: MSCT-CA provides important information regarding the coronary plaque
      burden in patients with stable and unstable angina.

PMID- 21892713
TI  - Prognostic value of Morise clinical score, calcium score and computed tomography
      coronary angiography in patients with suspected or known coronary artery disease.
AB  - PURPOSE: Our aim was to determine the prognostic value of computed tomography
      coronary angiography (CTCA), coronary artery calcium scoring (CACS) and Morise
      clinical score in patients with known or suspected coronary artery disease (CAD).
      MATERIALS AND METHODS: A total of 722 patients (480 men; 62.7+/-10.9 years) who
      were referred for further cardiac evaluation underwent CACS and contrast-enhanced
      CTCA to evaluate the presence and severity of CAD. Of these, 511 (71%) patients
      were without previous history of CAD. Patients were stratified according to the
      Morise clinical score (low, intermediate, high), to CACS (0-10, 11-100, 101-400,
      401-1,000, >1,000) and to CTCA (absence of CAD, nonsignificant CAD, obstructive
      CAD). Patients were followed up for the occurrence of major events: cardiac
      death, nonfatal myocardial infarction, unstable angina and revascularisation.
      RESULTS: Significant CAD (>50% luminal narrowing) was detected in 260 (36%)
      patients; nonsignificant CAD (<50% luminal narrowing) in 250 (35%) and absence of
      CAD in 212 (29%). During a mean follow-up of 20+/-4 months, 116 events (21 hard)
      occurred. In patients with normal coronary arteries on CTCA, the major event rate
      was 0% vs. 1.7% in patients with nonsignificant CAD and 7.3% in patients with
      significant CAD (p<0.0001). Three hard events (14%) occurred in patients with
      CACS<=100 and two (9.5%) in patients with intermediate Morise score; one
      revascularisation was observed in a patient with low Morise score. At
      multivariate analysis, diabetes, obstructive CAD and CACS >1,000 were significant
      predictors of events (p<0.05). CONCLUSIONS: An excellent prognosis was noted in
      patients with a normal CTCA (0% event rate). CACS <=100 and low-intermediate
      Morise score did not exclude the possibility of events at follow-up.

PMID- 21892714
TI  - MR-PET fusion imaging in evaluating adnexal lesions: a preliminary study.
AB  - PURPOSE: The objective of this preliminary study was to examine the effects of
      combined magnetic resonance/positron emission tomography (MR-PET) evaluation in
      the morphofunctional characterisation of ovarian lesions. MATERIALS AND METHODS:
      From June 2008 to September 2010, we evaluated 24 patients (mean age 44+/-10
      years; range 24-74) with ovarian lesions incidentally detected on ultrasonography
      (US) and/or multislice computed tomography (CT). All patients underwent MR
      imaging of the pelvis and total-body CT-PET. PET and MR images were subsequently
      fused at postprocessing using specific anatomical criteria. Results were compared
      with the histological examination. RESULTS: Of the 24 examined lesions, 19 were
      malignant and five were benign on histological examination. MR, CT-PET and MR-PET
      sensitivity was 84%, 74% and 94%, respectively and specificity 60%, 80% and 100%,
      respectively. Positive (PPV) and negative predictive (NPV) values were 93% and
      44% for CT-PET, 89% and 50% for MR and 100% and 83% for MR-PET, respectively.
      CONCLUSIONS: Pelvic MR-PET fusion imaging provides advantages in terms of
      sensitivity and especially specificity compared with MR imaging or CT-PET alone.
      The added value of this fusion imaging modality lies in combining the benefits of
      the morphological evaluation provided by MR imaging and the metabolic assessment
      provided by PET.

PMID- 21892715
TI  - Comparison between different kernel reformatting filters in 3D quantitative
      analysis of MDCT coronary angiography.
AB  - PURPOSE: Coronary angiography with multidetector-row computed tomography (MDCT
      CA) allows quantification of coronary artery stenosis with a high level of
      accuracy; however, a better estimation of stenosis can be achieved by using
      appropriate reformatting filters, especially in stents and calcified segments.
      Quantitative computed tomography angiography (QCTA) is intended to overcome the
      limitations of the visual score. The aim of this study was to evaluate the
      accuracy of QCTA with different filters in comparison with quantitative coronary
      angiography (QCA) and visual score. MATERIALS AND METHODS: Two blinded operators
      visually scored 17 consecutive patients referred for MDCT-CA with a per-segment
      analysis. The degree of stenosis was classified as 0-20%, 20-50% (wall
      irregularities), 50-70% (significant disease) and 70-100% (vessel occlusion).
      Each segment was then analysed using the electronic callipers of the QCTA system
      with 15 different filters. No contour editing was performed. Data were compared
      with QCA and conventional coronary angiography (CCA). Comparison between QCTA,
      visual score and QCA were performed using Spearman's rank correlation. RESULTS:
      Of 25 segments analysed (mean 1.4 diseased segment per patient), 375 measurements
      were considered. Good correlation was found between the visual score and QCA
      [Pearson correlation coefficient (rho=0.852; p<0.0001)] and between QCA and CCA
      (rho=0.804; p<0.0001). Moderate correlation was found between QCA and QCTA only
      using two filters (rho=0.444; p<0.0001 for YA filter and rho=0.450; p<0.0001 for
      YB filter). CONCLUSIONS: Overall QCTA accuracy is low if contour editing is not
      applied, especially in calcified vessels. Certain filters can help to better
      estimate the exact percentage of stenosis.

PMID- 21892716
TI  - Ultrasound contrast media in paediatric patients: is it an off-label use?
      Regulatory requirements and radiologist's liability.
AB  - The use of ultrasound contrast media is yet to be validated in children. The rare
      reports in the scientific literature denote their "sporadic" and "experimental"
      use. Their most likely use is in the setting of off-label prescription of
      medications. As there are still no guidelines available in Italy for the off
      label use of medications, we aim to define the duties, obligations and liability
      of ultrasound radiologists according to the laws in force.

PMID- 21892717
TI  - Endovascular treatment of ruptured abdominal aortic aneurysms: aorto-uni-iliac or
      bifurcated endograft?
AB  - PURPOSE: This study evaluated the safety and technical and clinical success rates
      of positioning endovascular endografts (EG) in ruptured abdominal aneurysms.
      MATERIALS AND METHODS: Patients with a ruptured abdominal aortic aneurysm
      confirmed by contrast-enhanced computed tomography angiography (CTA) were
      eligible for the analysis. Of 67 patients, 42 (62.7%) were treated with EG.
      Thirteen patients (30.9%) received an aorto-uni-iliac EG (group A) and 29 a
      bifurcated EG (group B). Patients were divided for comparative analysis according
      to the configuration of the EG implanted. RESULTS: The primary technical success
      rate was 100%; the primary clinical success rate was 95% (40/42). There were two
      intraoperative deaths (4.7%) related to intractable shock. No patient required
      conversion to open repair. Overall, 12 patients (28.5%) died within 30 days. The
      in-hospital death rate was 30.9% (13/42). Hospital mortality rate was
      statistically higher in group A; the type of EG and intensive care unit admission
      were the only independent predictors of hospital mortality. CONCLUSIONS: In our
      experience, a higher mortality rate was observed for the aorto-uni-iliac
      configuration; shock at admission was confirmed as the most important factor for
      postoperative survival.

PMID- 21892718
TI  - Acute toxicity in 14 patients with locally advanced head and neck squamous cell
      carcinoma treated with concurrent cetuximab and radiotherapy.
AB  - PURPOSE: The authors report acute toxicity in 14 patients with locally advanced
      head and neck squamous cell carcinoma treated with radiotherapy and cetuximab.
      MATERIALS AND METHODS: Data collection was performed prospectively on patients
      treated from September 2007 to March 2009. Treatment consisted of 64.8-70 Gy
      radiotherapy in conventional fractions and cetuximab. RESULTS: Two out of 14
      patients did not complete the planned combined treatment; radiotherapy was
      temporarily suspended in six other patients. Seven of 12 patients received
      cetuximab until the end of radiotherapy. Treatment breaks were principally due to
      severe acute cutaneous or mucous toxicity. Any grade acneiform rash occurred in
      all patients. In-field G3-4 cutaneous toxicity occurred in five (36%) patients
      and G3-4 mucous toxicity in seven (50%). One patient died of sepsis. CONCLUSIONS:
      In our experience, severe acute toxic reactions are common in patients treated
      with radiotherapy and concurrent cetuximab, resulting in frequent breaks or
      incomplete treatment with potential reduction in disease control.

PMID- 21892719
TI  - Clinical applications of dynamic susceptibility contrast perfusion-weighted MR
      imaging in brain tumours.
AB  - Magnetic resonance imaging (MRI) with a dynamic susceptibility contrast perfusion
      weighted imaging (DSC-PWI) sequence to study brain tumours provides information
      on the haemodynamic characteristics of the neoplastic tissue. Brain perfusion
      maps and calculation of perfusion parameters, such as relative cerebral blood
      flow (rCBF), relative cerebral blood volume (rCBV) and mean transit time (MTT)
      allow assessment of vascularity and angiogenesis within tumours of the central
      nervous system (CNS), thus providing additional information to conventional MRI
      sequences. Although DSC-PWI has long been used, its clinical use in the study of
      brain tumours in daily clinical practice is still to be defined. The aim of this
      review was to analyse the application of perfusion MRI in the study of brain
      tumours by summarising our personal experience and the main results reported in
      the literature.

PMID- 21892720
TI  - Adenomyosis: from the sign to the diagnosis. Imaging, diagnostic pitfalls and
      differential diagnosis: a pictorial review.
AB  - Adenomyosis is a pathological gynaecological condition characterised by benign
      invasion of the endometrium into the myometrium. It is often misdiagnosed, or is
      not easily recognised, although it is responsible for disabling symptoms such as
      menorrhagia, abnormal uterine bleeding, dysmenorrhoea and infertility in
      premenopausal women. The aim of this pictorial review is to analyse the features
      of adenomyosis by illustrating the most usual and typical imaging patterns, along
      with the unusual appearances, seen in a vast array of gynaecological imaging
      modalities. The different findings of focal and diffuse adenomyosis along with
      the diagnostic limitations of ultrasound, hysterosalpingography and magnetic
      resonance imaging are described, as are the pitfalls and differential diagnosis
      with other pathological conditions that are often misdiagnosed as adenomyosis.
      The role of the different imaging modalities in planning appropriate treatment
      and their usefulness in monitoring therapy are also discussed.

PMID- 21892721
TI  - Body iron stores as predictors of insulin resistance in apparently healthy urban
      Colombian men.
AB  - The aim of this study was to evaluate body iron stores as predictors of insulin
      resistance. We developed a cross-sectional study among 123 men, 25-64 years of
      age and determined fasting plasma glucose, insulin, serum ferritin, and C
      reactive protein levels. A survey was performed to record personal antecedents
      and family history of non-transmissible chronic diseases. Log-transformed
      ferritin levels was an independent predictor for log-transformed insulin
      resistance index assessed by homeostatic model assessment when body mass index or
      waist circumference were not included in multiple linear regression models.
      Sedentarism, heart attack family history, and log-C reactive protein levels were
      also significant predictors for insulin resistance. In conclusion, documented
      anthropometric predictors affect the significance of ferritin as a potential
      prediction variable for insulin resistance. Mechanisms of how body fat could
      influence ferritin levels should be evaluated. To our knowledge, this is the
      first evaluation of the relationship between body iron stores and insulin
      resistance in a Latin American population.

PMID- 21892722
TI  - Red fox Vulpes vulpes (L., 1758) as a bioindicator of mercury contamination in
      terrestrial ecosystems of north-western Poland.
AB  - In this study, we determined the concentrations of total mercury (Hg) in samples
      of liver, kidney and skeletal muscle of 27 red foxes Vulpes vulpes (L., 1758)
      from north-western Poland, and examined the morphometric characteristics of the
      collected specimens. The analysis also included the relationship between Hg
      concentration and the fox size, and the suitability of individual organs as
      bioindicators in indirect evaluation of environmental mercury contamination.
      Determination of Hg concentration was performed by atomic absorption
      spectroscopy. In the analysed samples, the Hg concentration was low and the
      maximum value did not exceed 0.85 mgHg/kg dry weight (dw). There were no
      significant differences in Hg concentrations in the analysed material between
      males and females or between immature and adult groups. The median concentrations
      of Hg in the liver, kidney and skeletal muscle were 0.22, 0.11 and 0.05 mgHg/kg
      dw, respectively. The correlation coefficients were significant between the
      concentrations of mercury in the liver, kidney and skeletal muscle (positive) and
      between the kidney Hg concentration and kidney mass (negative). Taking into
      account our results and findings of other authors, it may be argued that the red
      fox exhibits a measurable response to mercury environmental pollution and meets
      the requirements of a bioindicator.

PMID- 21892723
TI  - Scientific evaluation of modern clinical research: we need a new currency!

PMID- 21892704
TI  - The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in
      younger postmenopausal women and in those with chemotherapy-induced menopause.
AB  - Letrozole, an aromatase inhibitor, is ineffective in the presence of ovarian
      estrogen production. Two subpopulations of apparently postmenopausal women might
      derive reduced benefit from letrozole due to residual or returning ovarian
      activity: younger women (who have the potential for residual subclinical ovarian
      estrogen production), and those with chemotherapy-induced menopause who may
      experience return of ovarian function. In these situations tamoxifen may be
      preferable to an aromatase inhibitor. Among 4,922 patients allocated to the
      monotherapy arms (5 years of letrozole or tamoxifen) in the BIG 1-98 trial we
      identified two relevant subpopulations: patients with potential residual ovarian
      function, defined as having natural menopause, treated without adjuvant or
      neoadjuvant chemotherapy and age <= 55 years (n = 641); and those with
      chemotherapy-induced menopause (n = 105). Neither of the subpopulations examined
      showed treatment effects differing from the trial population as a whole
      (interaction P values are 0.23 and 0.62, respectively). Indeed, both among the
      641 patients aged <= 55 years with natural menopause and no chemotherapy (HR 0.77
      [0.51, 1.16]) and among the 105 patients with chemotherapy-induced menopause (HR
      0.51 [0.19, 1.39]), the disease-free survival (DFS) point estimate favoring
      letrozole was marginally more beneficial than in the trial as a whole (HR 0.84
      [0.74, 0.95]). Contrary to our initial concern, DFS results for young
      postmenopausal patients who did not receive chemotherapy and patients with
      chemotherapy-induced menopause parallel the letrozole benefit seen in the BIG 1
      98 population as a whole. These data support the use of letrozole even in such
      patients.

PMID- 21892724
TI  - Identification of host fruit volatiles from three mayhaw species (Crataegus
      series Aestivales) attractive to mayhaw-origin Rhagoletis pomonella flies in the
      southern United States.
AB  - The apple maggot fly, Rhagoletis pomonella, infests several hawthorn species in
      the southern USA. Here, we tested the hypothesis that these populations could
      serve as reservoirs for fruit odor discrimination behaviors facilitating
      sympatric host race formation and speciation, specifically the recent shift from
      downy hawthorn (Crataegus mollis) to domestic apple (Malus domestica) in the
      northern USA. Coupled gas chromatography and electroantennographic detection (GC
      EAD), gas chromatography with mass spectrometry (GC-MS), and flight tunnel
      bioassays were used to identify the behaviorally active natal fruit volatile
      blends for three of the five major southern hawthorns: C. opaca (western mayhaw),
      C. aestivalis (eastern mayhaw), and C. rufula (a possible hybrid between C. opaca
      and C. aestivalis). A 6-component blend was developed for C. opaca (3-methylbutan
      1-ol [44%], pentyl acetate [6%], butyl butanoate [6%], propyl hexanoate [6%],
      butyl hexanoate [26%], and hexyl butanoate [12%]); an 8-component blend for C.
      aestivalis (3-methylbutan-1-ol [2%], butyl acetate [47%], pentyl acetate [2%],
      butyl butanoate [12%], propyl hexanoate [1%], butyl hexanoate [25%], hexyl
      butanoate [9%], and pentyl hexanoate [2%]); and a 9-component blend for C. rufula
      (3-methylbutan-1-ol [1%], butyl acetate [57%], 3-methylbutyl acetate [3%], butyl
      butanoate [5%], propyl hexanoate [1%], hexyl propionate [1%], butyl hexanoate
      [23%], hexyl butanoate [6%], and pentyl hexanoate [3%]). Crataegus aestivalis and
      C. opaca-origin flies showed significantly higher levels of upwind directed
      flight to their natal blend in flight tunnel assays compared to the non-natal
      blend and previously developed apple, northern downy hawthorn, and flowering
      dogwood blends. Eastern and western mayhaw flies also were tested to the C.
      rufula blend, with eastern flies displaying higher levels of upwind flight
      compared with the western flies, likely due to the presence of butyl acetate in
      the C. aestivalis and C. rufula blends, an agonist compound for eastern mayhaw
      origin flies, but a behavioral antagonist for western flies. The results discount
      the possibility that the apple fly was "pre-assembled" and originated via a
      recent introduction of southern mayhaw flies predisposed to accepting apple.
      Instead, the findings are consistent with the possibility of southern mayhaw
      infesting fly host races. However, mayhaw fruits do emit several volatiles found
      in apple. It is, therefore, possible that the ability of the fly to evolve a
      preference for apple volatiles, although not the entire blend, stemmed, in part,
      from standing variation related to the presence of these compounds in southern
      mayhaw fruit.

PMID- 21892725
TI  - Cervical cancer control: deaf and hearing women's response to an educational
      video.
AB  - Deaf people encounter barriers to accessing cancer information. In this study, a
      graphically enriched educational video about cervical cancer was created in
      American Sign Language, with English open captioning and voice overlay. Deaf (n =
      127) and hearing (n = 106) women completed cancer knowledge surveys before and
      after viewing the video. Hearing women yielded higher scores before the
      intervention. Both groups demonstrated a significant increase in general and
      cervical cancer knowledge after viewing the video, rendering posttest knowledge
      scores nearly equal between the groups. These findings indicate that this video
      is an effective strategy for increasing cervical cancer knowledge among deaf
      women.

PMID- 21892726
TI  - Calcium-dependent decrease in the single-channel conductance of TRPV1.
AB  - TRPV1 is a Ca(2+) permeable cation channel gated by multiple stimuli including
      noxious heat, capsaicin, protons, and extracellular cations. In this paper, we
      show that Ca(2+) causes a concentration and voltage-dependent decrease in the
      capsaicin-gated TRPV1 single-channel conductance. This Ca(2+)-dependent effect on
      conductance was strongest at membrane potentials between -60 and +20 mV, but was
      diminished at more hyperpolarised potentials. Using simultaneous recordings of
      membrane current and fura-2 fluorescence to measure the fractional Ca(2+) current
      of whole-cell currents evoked through wild-type and mutant TRPV1, we investigated
      a possible link between the mechanisms underlying Ca(2+) permeation and the
      Ca(2+)-dependent effect on conductance. Surprisingly, we found no evidence of a
      structural correlation, and observed that the substitution of amino acids known
      to regulate Ca(2+) permeability had little effect on the ability for Ca(2+) to
      decrease TRPV1 conductance. However, we did observe that the Ca(2+)-dependent
      effect on conductance was not diminished by negative hyperpolarisation for a
      mutant receptor with severely impaired Ca(2+) permeability, TRPV1
      D646N/E648Q/E651Q. This would be consistent with the idea that Ca(2+) reduces
      conductance by interacting with an intra-pore binding site, and that negative
      hyperpolarization reduces occupancy of this site by speeding the exit of Ca(2+)
      into the cell. Taken together, our data show that in addition to directly and
      indirectly regulating channel gating, Ca(2+) also directly reduces the
      conductance of TRPV1. Surprisingly, the mechanism underlying this Ca(2+)
      dependent effect on conductance is largely independent of mechanisms governing
      Ca(2+) permeability.

PMID- 21892728
TI  - EXT2-positive multiple hereditary osteochondromas with some features suggestive
      of metachondromatosis.
AB  - Metachondromatosis (MC) and hereditary multiple osteochondromas (HMO) are thought
      to be distinct disorders, each with characteristic x-ray and clinical features.
      Radiographic differences are the current mainstay of differential diagnosis. Both
      disorders are autosomal dominant, but the majority of patients with HMO have
      mutations in EXT-1 or EXT 2 genes. The genetic defect in MC is unknown, although
      recent studies indicate a possible identifiable mutation. The cancer risk in HMO
      is thought to be greater than in MC, although the small number of cases make such
      conjecture imprecise. The purpose of this report is to review existing literature
      and examine whether radiographic findings in HMO and MC can be reliable as a
      stand-alone means of differential diagnosis. Three members of a multi
      generational family with an autosomal dominant exostosis syndrome were studied by
      clinical examination and complete skeletal survey. The roentgenographic
      characteristics of all osteochondromas were analyzed. The father underwent gene
      sequencing for EXT-1 and EXT-2, which revealed a novel EXT-2 mutation. Typical
      radiographic and clinical findings of both HMO and MC were seen throughout the
      family as well as in individuals. These family study findings contradict many of
      the long-standing clinical and x-ray diagnostic criteria for differentiating MC
      from HMO. The phenotypic crossover between the two conditions in this family, and
      results of genetic analysis, suggest that in the absence of a definitive genetic
      diagnosis, radiographic and clinical diagnosis of past and future cases HMO and
      MC may not be as reliable as previously assumed.

PMID- 21892727
TI  - Activity of cortical and thalamic neurons during the slow (<1 Hz) rhythm in the
      mouse in vivo.
AB  - During NREM sleep and under certain types of anaesthesia, the mammalian brain
      exhibits a distinctive slow (<1 Hz) rhythm. At the cellular level, this rhythm
      correlates with so-called UP and DOWN membrane potential states. In the
      neocortex, these UP and DOWN states correspond to periods of intense network
      activity and widespread neuronal silence, respectively, whereas in
      thalamocortical (TC) neurons, UP/DOWN states take on a more stereotypical
      oscillatory form, with UP states commencing with a low-threshold Ca(2+) potential
      (LTCP). Whilst these properties are now well recognised for neurons in cats and
      rats, whether or not they are also shared by neurons in the mouse is not fully
      known. To address this issue, we obtained intracellular recordings from
      neocortical and TC neurons during the slow (<1 Hz) rhythm in anaesthetised mice.
      We show that UP/DOWN states in this species are broadly similar to those observed
      in cats and rats, with UP states in neocortical neurons being characterised by a
      combination of action potential output and intense synaptic activity, whereas UP
      states in TC neurons always commence with an LTCP. In some neocortical and TC
      neurons, we observed 'spikelets' during UP states, supporting the possible
      presence of electrical coupling. Lastly, we show that, upon tonic depolarisation,
      UP/DOWN states in TC neurons are replaced by rhythmic high-threshold bursting at
      ~5 Hz, as predicted by in vitro studies. Thus, UP/DOWN state generation appears
      to be an elemental and conserved process in mammals that underlies the slow (<1
      Hz) rhythm in several species, including humans.

PMID- 21892729
TI  - Is bone scintigraphy necessary in the initial surgical staging of chondrosarcoma
      of bone?
AB  - OBJECTIVE: To assess the value of whole-body bone scintigraphy in the initial
      surgical staging of chondrosarcoma of bone. METHODS: A retrospective review was
      conducted of the bone scintigraphy reports of a large series of patients with
      peripheral or central chondrosarcoma of bone treated in a specialist orthopaedic
      oncology unit over a 13-year period. Abnormal findings were correlated against
      other imaging, histological grade and the impact on surgical staging. RESULTS: A
      total of 195 chondrosarcomas were identified in 188 patients. In 120 (63.8%)
      patients the reports of bone scintigraphy noted increased activity at the site of
      one or more chondrosarcomas. In one patient the tumour was outside the field-of
      view of the scan, and in the remaining 67 (35.6%) cases, there was increased
      activity at the site of the chondrosarcoma and further abnormal activity in other
      areas of the skeleton. Causes of these additional areas of activity included
      degenerative joint disease, Paget's disease and in one case a previously
      undiagnosed melanoma metastasis. No cases of skeletal metastases from the
      chondrosarcoma were found in this series. Multifocal chondrosarcomas were
      identified in three cases. In two it was considered that all the tumours would
      have been adequately revealed on the initial MR imaging staging studies. In only
      the third multifocal case was an unsuspected, further presumed low-grade, central
      chondrosarcoma identified in the opposite asymptomatic femur. Although this case
      revealed an unexpected finding the impact on surgical staging was limited as it
      was decided to employ a watch-and-wait policy for this tumour. CONCLUSION: There
      is little role for the routine use of whole-body bone scintigraphy in the initial
      surgical staging in patients with chondrosarcoma of bone irrespective of the
      histological grade.

PMID- 21892730
TI  - Functional features of a single chromosome arm in wheat (1AL) determined from its
      structure.
AB  - Bread wheat (Triticum aestivum L.) is one of the most important crops globally
      and a high priority for genetic improvement, but its large and complex genome has
      been seen as intractable to whole genome sequencing. Isolation of individual
      wheat chromosome arms has facilitated large-scale sequence analyses. However, so
      far there is no such survey of sequences from the A genome of wheat. Greater
      understanding of an A chromosome could facilitate wheat improvement and future
      sequencing of the entire genome. We have constructed BAC library from the long
      arm of T. aestivum chromosome 1A (1AL) and obtained BAC end sequences from 7,470
      clones encompassing the arm. We obtained 13,445 (89.99%) useful sequences with a
      cumulative length of 7.57 Mb, representing 1.43% of 1AL and about 0.14% of the
      entire A genome. The GC content of the sequences was 44.7%, and 90% of the
      chromosome was estimated to comprise repeat sequences, while just over 1% encoded
      expressed genes. From the sequence data, we identified a large number of sites
      suitable for development of molecular markers (362 SSR and 6,948 ISBP) which will
      have utility for mapping this chromosome and for marker assisted breeding. From
      44 putative ISBP markers tested 23 (52.3%) were found to be useful. The BAC end
      sequence data also enabled the identification of genes and syntenic blocks
      specific to chromosome 1AL, suggesting regions of particular functional interest
      and targets for future research.

PMID- 21892732
TI  - Primary malignant melanoma of the female urethra: 10-year survival.

PMID- 21892733
TI  - A novel tool for estimation of magnetic resonance occupational exposure to
      spatially varying magnetic fields.
AB  - OBJECT: Staff operating in the environment of magnetic resonance imaging (MRI)
      scanners are exposed daily to static magnetic fields (MFs). To protect workers
      several guidelines are present in literature reporting exposure limits values
      expressed in terms of magnetic flux density or induced current density. We
      present here a novel tool for estimating the induced current density due to
      worker movement in the MR environment. MATERIALS AND METHODS: A Matlab script was
      created to estimate the induced current density J due to operator movements along
      a chosen walking path. RESULTS: The induced current density associated with any
      worker's movements during MR procedures is dependent on the walking speed and on
      the spatial gradient fields associated with a specific path. Some examples of
      possible worker paths were considered here for a 3 T MR scanner and a maximum
      value of 160 cm/s walking speed. CONCLUSION: This tool permits one to find
      exposure level for specific worker walking path and speed; it can be used as
      assessment tool in any MRI centre and for workers safety education. It is valid
      for any kind of commercial scanner because it requires only the knowledge of the
      MR scanner room map with isogauss lines.

PMID- 21892731
TI  - Emerging roles of epigenetic mechanisms in Parkinson's disease.
AB  - Epigenetic mechanisms have emerged as important components of a variety of human
      diseases, including cancer and central nervous system disorders. Despite recent
      studies highlighting the role of epigenetic mechanisms in several
      neurodegenerative and neuropsychiatric disorders, to date, there has been a
      paucity of studies exploring the role of epigenetic factors in Parkinson's
      disease (PD). PD is a progressive neurological disorder with characteristic motor
      and non-motor symptoms, including a range of neuropsychiatric features, for which
      neither preventative nor effective long-term treatment strategies are available.
      It is one of the most common neurodegenerative disorders and the second most
      prevalent after Alzheimer's disease. In this review, we present several lines of
      evidence suggesting that epigenetic factors may play an important role in the
      pathogenesis of PD and propose on this basis a framework to guide future
      investigations into epigenetic mechanisms and systems biology of PD. These
      notions, together with technical advances in the ability to perform genome-wide
      analysis of epigenomic states, and newly available small-molecule probes
      targeting chromatin-modifying enzymes, may help design new treatment strategies
      for PD and other human diseases involving epigenetic dysregulation.

PMID- 21892734
TI  - 1H-MRS of hepatic fat using short TR at 3T: SNR optimization and fast T2
      relaxometry.
AB  - OBJECT: To increase the signal-to-noise ratio (SNR) efficiency of hepatic fat
      signals in proton magnetic resonance spectroscopy (1H MRS) at 3 T, in order to
      improve the quantitation of hepatic fat and allow fast, single breath-hold T2
      relaxometry of hepatic water and fat. MATERIALS AND METHODS: Since the T1 of
      lipid protons is relatively short, we hypothesized that it could be possible to
      increase the lipid SNR efficiency by choosing a TR shorter than that typically
      employed (>=1.5 s). The lipid SNR per unit-time was calculated using published
      values of lipid (CH2)n protons' T1 at 3 T. 1H MRS PRESS spectra were acquired
      from VOIs located in the right lobe of the liver in 28 healthy volunteers. At the
      short TR of 0.6 s, fast T2 relaxometry with the acquisition of 16 echo times (30,
      40, ..., 180 ms), was performed in a single breath-hold measurement using a
      modified PRESS sequence. RESULTS: Good agreement was observed between simulated
      and experimental data, with the shortening of TR to 0.6 s yielding an ~50% SNR
      improvement of hepatic lipid (CH2)n resonances, compared to the SNR at TR=2 s.
      The T2 relaxation time of water and lipid (CH2)n protons at 3 T was 25.8+/-1.1 ms
      and 55.4+/-3.9 ms, respectively, across five healthy volunteers. CONCLUSION: The
      short-TR approach allows for an improved SNR efficiency of lipids and for fast T2
      relaxometry of hepatic water and fat, with a detailed coverage of the T2
      relaxation decay curve, within a single breath-hold experiment.

PMID- 21892735
TI  - Characterization of human clinical isolates of Dietzia species previously
      misidentified as Rhodococcus equi.
AB  - In this study, 16 human clinical isolates of Dietzia species previously
      misidentified as Rhodococcus equi were evaluated using phenotypic methods,
      including traditional and commercial (API Coryne) biochemical tests,
      antimicrobial susceptibility testing, and 16S rRNA gene and gyrB gene sequencing.
      Positive results for both the hydrolysis of adenine and Christie-Atkins-Munch
      Petersen (CAMP) reaction allowed for differentiation between the Dietzia isolates
      and the type strain of Rhodococcus equi; however, traditional and commercial
      phenotypic profiles could not be used to reliably identify Dietzia species. The
      analysis of 16S rRNA gene and gyrB gene sequences could discriminate all Dietzia
      strains from the type strain of R. equi. Most Dietzia species had distinct 16S
      rRNA gene and gyrB gene sequences; however, the 16S rRNA gene sequences of the
      type strains of D. schimae and D. cercidiphylli were identical to D. maris and D.
      natronolimnaea, respectively. Based on comparative sequence analysis, five
      clinical isolates clustered with D. maris/D. schimae and nine with D.
      natronolimnaea/D. cercidiphylli. The two remaining isolates were found to be most
      closely related to the D. cinnamea/D. papillomatosis clade. Even though molecular
      analyses were not sufficiently discriminative to accurately identify all Dietzia
      species, the method was able to reliably identify isolates that were previously
      misidentified by phenotypic methods to the genus level.

PMID- 21892736
TI  - Analysis of heat-induced disassembly process of three different monomeric forms
      of the major light-harvesting chlorophyll a/b complex of photosystem II.
AB  - The temperature-dependent disassembly process of three monomeric isoforms, namely
      Lhcb1, Lhcb2, and Lhcb3, of the major light-harvesting chlorophyll (Chl) a/b
      complexes of photosystem II (LHCIIb) were characterized by observing the changes
      of absorption spectra, circular dichroism (CD), and dissociation processes of the
      bound pigments to the in vitro reconstituted complexes subjected to high
      temperatures. Our results suggest that the three isoforms of LHCIIb undergo
      conformational rearrangements, structural changes, and dissociations of the bound
      pigments when the ambient temperature increases from 20 to 90 degrees C. The
      conformation of the complexes changed sensitively to the changing temperatures
      because the absorption peaks in the Soret region (436 and 471 nm) and the Qy
      region (650-660 and 680 nm) decreased immediately upon elevating the ambient
      temperatures. Analyzing temperature-dependent denaturing and pigment dissociation
      process, we can divide the disassembly process into three stages: The first
      stage, appeared from 20 degrees C to around 50-60 degrees C, was characterized by
      the diminishment of the absorption around 650-660 and 680 nm, accompanied by the
      blue-shift of the peak at 471 nm and disappearance of the absorbance at 436 nm,
      which is related to changes in the transition energy of the Chl b cluster, and
      the red-most Chl a cluster in the LHCIIb. The second stage, beginning at about 50
      60 degrees C, was signified by the diminishment of the CD signal between (+)483
      nm and (-)490 nm, which implied the disturbance of dipole-dipole interaction of
      pigments, and the onset of the pigment dissociation. The last stage, beginning at
      about 70-80 degrees C, indicates the complete dissociation of the pigments from
      the complex. The physiological aspects of the three stages in the denaturing
      process are also discussed.

PMID- 21892737
TI  - Expression pattern of two paralogs of the PI/GLO-like locus during Orchis italica
      (Orchidaceae, Orchidinae) flower development.
AB  - The class B MADS-box genes belong to two distinct functional groups: the AP3/DEF
      like and the PI/GLO-like sub-families. In orchids, AP3/DEF-like genes are present
      in four copies, each with a different role in floral organ formation, which is
      described in the "orchid code" model. Interestingly, the orchid PI/GLO-like genes
      are present in two copies in Orchidinae, whereas they are described as single
      copy in the other orchid lineages. The two PI/GLO-like paralogs have site
      specific different selective constraints; in addition, they show relaxation of
      purifying selection when compared to the single-copy lineages. In this study, we
      present a comparative analysis of the expression patterns of the two PI/GLO-like
      paralogs, OrcPI and OrcPI2, in floral tissues of Orchis italica in different
      developmental stages using real-time PCR. The two genes show similar expression
      profiles in the tissue examined, with differences detectable between immature and
      mature inflorescence. In all cases, OrcPI2 is expressed at a higher level than
      OrcPI. Real-time PCR results reveal that the co-expression of the two duplicated
      loci could have a fully or partially redundant function. The possible
      evolutionary fate of OrcPI and OrcPI2 is discussed as well as their involvement
      in ovary development.

PMID- 21892738
TI  - Wnt gene loss in flatworms.
AB  - Wnt genes encode secreted glycoproteins that act in cell-cell signalling to
      regulate a wide array of developmental processes, ranging from cellular
      differentiation to axial patterning. Discovery that canonical Wnt/beta-catenin
      signalling is responsible for regulating head/tail specification in planarian
      regeneration has recently highlighted their importance in flatworm (phylum
      Platyhelminthes) development, but examination of their roles in the complex
      development of the diverse parasitic groups has yet to be conducted. Here, we
      characterise Wnt genes in the model tapeworm Hymenolepis microstoma and mine
      genomic resources of free-living and parasitic species for the presence of Wnts
      and downstream signalling components. We identify orthologs through a combination
      of BLAST and phylogenetic analyses, showing that flatworms have a highly reduced
      and dispersed complement that includes orthologs of only five subfamilies (Wnt1,
      Wnt2, Wnt4, Wnt5 and Wnt11) and fewer paralogs in parasitic flatworms (5-6) than
      in planarians (9). All major signalling components are identified, including
      antagonists and receptors, and key binding domains are intact, indicating that
      the canonical (Wnt/beta-catenin) and non-canonical (planar cell polarity and
      Wnt/Ca(2+)) pathways are functional. RNA-Seq data show expression of all
      Hymenolepis Wnts and most downstream components in adults and larvae with the
      notable exceptions of wnt1, expressed only in adults, and wnt2 expressed only in
      larvae. The distribution of Wnt subfamilies in animals corroborates the idea that
      the last common ancestor of the Cnidaria and Bilateria possessed all contemporary
      Wnts and highlights the extent of gene loss in flatworms.

PMID- 21892739
TI  - Intravascular ultrasound assessment of the association between spatial
      orientation of ruptured coronary plaques and remodeling morphology of culprit
      plaques in ST-elevation acute myocardial infarction.
AB  - The aim of this study was to assess the association between the spatial location
      of plaque rupture and remodeling pattern of culprit lesions in acute anterior
      myocardial infarction (MI). Positive remodeling suggests a potential surrogate
      marker of plaque vulnerability, whereas plaque rupture causes thrombus formation
      followed by coronary occlusion and MI. Intravascular ultrasound (IVUS) can
      determine the precise spatial orientation of coronary plaque formation. We
      studied 52 consecutive patients with acute anterior MI caused by plaque rupture
      of the culprit lesion as assessed by preintervention IVUS. The plaques were
      divided into those with and without positive remodeling. We divided the plaques
      into three categories according to the spatial orientation of plaque rupture
      site: myocardial (inner curve), epicardial (outer curve), and lateral quadrants
      (2 intermediate quadrants). Among 52 plaque ruptures in 52 lesions, 27 ruptures
      were oriented toward the epicardial side (52%), 18 toward the myocardial side
      (35%), and 7 in the 2 lateral quadrants (13%). Among 35 plaques with positive
      remodeling, plaque rupture was observed in 21 (52%) on the epicardial side, 12
      (34%) on the myocardial side, and 2 (6%) on the lateral side. However, among 17
      plaques without positive remodeling, plaque rupture was observed in 6 (35%), 6
      (35%), and 5 (30%), respectively (p = 0.047). Atherosclerotic plaques with
      positive remodeling showed more frequent plaque rupture on the epicardial side of
      the coronary vessel wall in anterior MI than those without positive remodeling.

PMID- 21892740
TI  - The correlation between the cardio-ankle vascular index (CAVI) and serum amyloid
      A in asymptomatic Japanese subjects.
AB  - Chronic inflammation has received a great deal of attention due to the role it
      plays in cardiovascular disease (CVD). The cardio-ankle vascular index (CAVI) has
      recently been developed to evaluate arterial stiffness. This index is independent
      of blood pressure at the time that it is measured, making it a better measure for
      clinical studies on the prevention of CVD. Information on the association of
      serum amyloid A (SAA) with arterial stiffness in relatively healthy subjects is
      still scarce. The aim of the present study was to investigate the potential
      correlation between SAA and CAVI in asymptomatic Japanese subjects. In addition
      to SAA and CAVI, data on smoking status, body mass index, blood pressure, and
      serum/plasma biochemical indices such as glucose and total cholesterol were
      collected in 387 nonmedicated and CVD-free adult subjects during a health check
      examination (male/female 191/196, mean age 61.8 years). Among them, a randomly
      selected subgroup of 256 subjects (male/female 133/123, mean age 62.4 years) had
      a full dataset, including low-density lipoprotein cholesterol, high-density
      lipoprotein cholesterol, triglyceride, and hemoglobin A1c. Among the whole
      population, CAVI levels were significantly higher in males than in females [mean
      8.5 +/- (SD 1.1) vs. 8.2 +/- 1.1, p < 0.05], while SAA levels were slightly but
      nonsignificantly higher in females than in males [median 6.4 (interquartile range
      4.0-9.3) MUg/mL vs. 5.1 (3.5-8.4)]. In a multiple linear regression analysis,
      CAVI was weakly but significantly, independently, and positively correlated with
      SAA (beta-coefficient 0.200, p < 0.01). The results of the same analyses for the
      randomly selected subgroup were relatively similar to the findings for the whole
      population. SAA may be a positive inflammatory factor associated with arterial
      stiffness, and the clinical relevance and the biological mechanism for this
      relationship should be established in future studies.

PMID- 21892741
TI  - Dosimetric comparison of Linac-based (BrainLAB(r)) and robotic radiosurgery
      (CyberKnife (r)) stereotactic system plans for acoustic schwannoma.
AB  - A dosimetric comparison of linear accelerator (LA)-based (BrainLAB) and robotic
      radiosurgery (RS) (CyberKnife) systems for acoustic schwannoma (Acoustic neuroma,
      AN) was carried out. Seven patients with radiologically confirmed unilateral AN
      were planned with both an LA-based (BrainLAB) and robotic RS (CyberKnife) system
      using the same computed tomography (CT) dataset and contours. Gross tumour volume
      (GTV) was contoured on post-contrast magnetic resonance imaging (MRI) scan
      [planning target volume (PTV) margin 2 mm]. Planning and calculation were done
      with appropriate calculation algorithms. The prescribed isodose in both systems
      was considered adequate to cover at least 95% of the contoured target. Plan
      evaluations were done by examining the target coverage by the prescribed isodose
      line, and high- and low-dose volumes. Isodose plans and dose volume histograms
      generated by the two systems were compared. There was no statistically
      significant difference between the contoured volumes between the systems. Tumour
      volumes ranged from 380 to 3,100 mm(3). Dose prescription was 13-15 Gy in single
      fraction (median prescribed isodose 85%). There were no significant differences
      in conformity index (CI) (0.53 versus 0.58; P = 0.225), maximum brainstem dose
      (4.9 versus 4.7 Gy; P = 0.935), 2.5-Gy volume (39.9 versus 52.3 cc; P = 0.238) or
      5-Gy volume (11.8 versus 16.8 cc; P = 0.129) between BrainLAB and CyberKnife
      system plans. There were statistically significant differences in organs at risk
      (OAR) doses, such as mean cochlear dose (6.9 versus 5.4 Gy; P = 0.001), mean
      mesial temporal dose (2.6 versus 1.7 Gy; P = 0.07) and high-dose (10 Gy) volume
      (3.2 versus 5.2 cc; P = 0.017). AN patients planned with the CyberKnife system
      had superior OAR (cochlea and mesial temporal lobe) sparing compared with those
      planned with the Linac-based system. Further evaluation of these findings in
      prospective studies with clinical correlation will provide actual clinical
      benefit from the dosimetric superiority of CyberKnife.

PMID- 21892742
TI  - Evidence for involvement of ROCK signaling in bradykinin-induced increase in
      murine blood-tumor barrier permeability.
AB  - We have previously shown that activation of RhoA by bradykinin (BK) is associated
      with cytoskeleton rearrangement, tight junction (TJ) protein disassembly, and an
      increase in blood-tumor barrier (BTB) permeability in rat brain microvascular
      endothelial cells (RBMECs). Subsequently, we investigated whether Rho-kinases
      (ROCKs), a family of downstream effectors of activated RhoA known to stimulate F
      actin rearrangement, play a key role in the above-mentioned processes in RBMECs.
      Our study uses primary RBMECs as an in vitro BTB model and a specific ROCK
      inhibitor (Y-27632) and ROCK II small interfering RNA (siRNA) to establish
      whether ROCK plays a role in the process of TJ opening by BK. Y-27632 and ROCK II
      siRNA could partially inhibit endothelial leakage and restored normal
      transendothelial electric resistance (TEER) values in RBMECs. A shift in occludin
      and claudin-5 distribution from insoluble to soluble fractions was prevented by Y
      27632. Additionally, Y-27632 inhibited BK-induced relocation of occludin and
      claudin-5 from cellular borders into the cytoplasm as well as stress fiber
      formation in RBMECs. A time-dependent increase in phosphorylated myosin light
      chain (p-MLC) and phosphorylated cofilin (p-cofilin) by BK was observed, which
      was also inhibited by Y-27632. An increase in ROCK activity by BK was inhibited
      by Y-27632. ROCK's contribution to BK-induced stress fiber formation is
      associated with TJ disassembly and an increase in BTB permeability.

PMID- 21892743
TI  - Cellular mechanisms in mitral valve disease.
AB  - The mitral valve is a living structure comprised of specific structural
      components which contain a heterogeneous population of cells. The cells include
      an amalgam of interstitial cells within the valve and a continuous covering of
      endothelial cells, each of which play a role in responding to the mechanical
      forces that the valve experiences, to maintain the function and durability of the
      valve. Attention on the characteristics and function of valve cells has focused
      mainly on those in the aortic valve, with relatively few studies addressing the
      role of these cells in the physiological and pathophysiological function of the
      mitral valve. This article reviews what is known about the function of cells
      within the mitral valve and how the changes in the physical and chemical
      environments can affect their function in the different types of mitral valve
      disease. Investigating the contribution of the cellular components of the mitral
      valve to valve function in health and disease will aid the understanding of how
      the durability and function of the valve are regulated, and possibly highlight
      molecular and pharmacological targets for the development of novel treatments for
      mitral valve disease.

PMID- 21892745
TI  - EphB signaling inhibits gap junctional intercellular communication and
      synchronized contraction in cultured cardiomyocytes.
AB  - Eph receptors and ephrin ligands are membrane-bound cell-cell communication
      molecules with important roles not only in development but also in the physiology
      of many adult organs. However, their cellular localization and functions in the
      myocardium are virtually unknown and therefore, we have investigated the
      expression of EphB receptors and ephrin-B ligands in the rodent heart ventricles
      and their functions in the rodent cardiomyocytes of primary culture. Examinations
      by RT-PCR, immunohistochemistry and in situ hybridization revealed that the EphB
      receptors are preferentially expressed in cardiomyocytes and ephrin-B ligands in
      the vasculature in adult mouse heart ventricles. Interestingly, we found that
      inducing high levels of EphB receptor activation in primary cultures of rodent
      cardiomyocytes by stimulation with ephrin-B1-Fc desynchronized the contraction of
      adjacent clusters of cardiomyocytes that had contracted synchronously before the
      treatment. Co-immunoprecipitation experiments revealed that EphB4 physically
      associates with connexin43, a major component of gap junctions in the myocardium,
      and that EphB activation inhibits gap junctional intracellular communication
      between cardiomyocytes. The present findings suggest that ephrin-B-EphB signaling
      can modulate the electrical coupling of cardiomyocytes through effects on gap
      junctions.

PMID- 21892746
TI  - The potential effects of anti-diabetic medications on myocardial ischemia
      reperfusion injury.
AB  - Heart disease and stroke account for 65% of the deaths in people with diabetes
      mellitus (DM). DM and hyperglycemia cause systemic inflammation, endothelial
      dysfunction, a hypercoagulable state with impaired fibrinolysis and increased
      platelet degranulation, and reduced coronary collateral blood flow. DM also
      interferes with myocardial protection afforded by preconditioning and
      postconditioning. Newer anti-diabetic agents should not only reduce serum glucose
      and HbA1c levels, but also improve cardiovascular outcomes. The older
      sulfonylurea agent, glyburide, abolishes the benefits of ischemic and
      pharmacologic preconditioning, but newer sulfonylurea agents, such as
      glimepiride, may not interfere with preconditioning. GLP-1 analogs and
      sitagliptin, an oral dipeptidyl peptidase IV inhibitor, limit myocardial infarct
      size in animal models by increasing intracellular cAMP levels and activating
      protein kinase A, whereas metformin protects the heart by activating AMP
      activated protein kinase. Both thiazolidinediones (rosiglitazone and
      pioglitazone) limit infarct size in animal models. The protective effect of
      pioglitazone is dependent on downstream activation of cytosolic phospholipase
      A(2) and cyclooxygenase-2 with subsequent increased production of 15-epi-lipoxin
      A(4), prostacyclin and 15-d-PGJ(2). We conclude that agents used to treat DM have
      additional actions that have been shown to affect the ability of the heart to
      protect itself against ischemia-reperfusion injury in preclinical models.
      However, the effects of these agents in doses used in the clinical setting to
      minimize ischemia-reperfusion injury and to affect clinical outcomes in patients
      with DM have yet to be shown. The clinical implications as well as the mechanisms
      of protection should be further studied.

PMID- 21892744
TI  - Biomaterials to prevascularize engineered tissues.
AB  - Tissue engineering promises to restore tissue and organ function following injury
      or failure by creating functional and transplantable artificial tissues. The
      development of artificial tissues with dimensions that exceed the diffusion limit
      (1-2 mm) will require nutrients and oxygen to be delivered via perfusion (or
      convection) rather than diffusion alone. One strategy of perfusion is to
      prevascularize tissues; that is, a network of blood vessels is created within the
      tissue construct prior to implantation, which has the potential to significantly
      shorten the time of functional vascular perfusion from the host. The
      prevascularized network of vessels requires an extracellular matrix or scaffold
      for 3D support, which can be either natural or synthetic. This review surveys the
      commonly used biomaterials for prevascularizing 3D tissue engineering constructs.

PMID- 21892747
TI  - NF-kappaB in the paraventricular nucleus modulates neurotransmitters and
      contributes to sympathoexcitation in heart failure.
AB  - Findings from our laboratory indicate that proinflammatory cytokines and their
      transcription factor, nuclear factor-kappaB (NF-kappaB), are increased in the
      hypothalamic paraventricular nucleus (PVN) and contribute towards the progression
      of heart failure. In this study, we determined whether NF-kappaB activation
      within the PVN contributes to sympathoexcitation via interaction with
      neurotransmitters in the PVN during the pathogenesis of heart failure. Heart
      failure was induced in rats by left anterior descending coronary artery ligation.
      Sham-operated control (SHAM) or heart failure rats were treated for 4 weeks
      through bilateral PVN infusion with SN50, SN50M or vehicle via osmotic minipump.
      Rats with heart failure treated with PVN vehicle or SN50M (inactive peptide for
      SN50) had increased levels of glutamate, norepinephrine (NE), tyrosine
      hydroxylase (TH), superoxide, gp91(phox) (a subunit of NAD(P)H oxidase),
      phosphorylated IKKbeta and NF-kappaB p65 activity, and lower levels of gamma
      aminobutyric acid (GABA) and the 67-kDa isoform of glutamate decarboxylase
      (GAD67) in the PVN compared with those of SHAM rats. Plasma levels of cytokines,
      norepinephrine, epinephrine and angiotensin II, and renal sympathetic nerve
      activity (RSNA) were increased in heart failure rats. Bilateral PVN infusion of
      SN50 prevented the decreases in PVN GABA and GAD67, and the increases in RSNA and
      PVN glutamate, norepinephrine, TH, superoxide, gp91(phox), phosphorylated IKKbeta
      and NF-kappaB p65 activity observed in vehicle or SN50M-treated heart failure
      rats. A same dose of SN50 given intraperitoneally did not affect
      neurotransmitters concentration in the PVN and was similar to vehicle-treated
      heart failure rats. These findings suggest that NF-kappaB activation in the PVN
      modulates neurotransmitters and contributes to sympathoexcitation in rats with
      ischemia-induced heart failure.

PMID- 21892749
TI  - Semirigid ureteroscopy: the effect of previous ipsilateral intraureteral
      manipulations on stone clearance.
AB  - We investigated whether previous intraureteral manipulations had an effect on the
      stone-free rates (SFR) after semi-rigid ureteroscopy (URS) with pneumatic
      lithotripsy. A retrospective review of all patients who were treated for ureteral
      stones at two different institutions from June 2003 through January 2010 was
      performed. Data of 161 URS procedures were analyzed. Stone size, location
      (distal, mid and proximal) and number (single and multiple), patient demographics
      and previous intraureteral manipulations were recorded. Patients were grouped as
      having undergone a previous ipsilateral intraureteral manipulation (Group 1) or
      not (Group 2). Stone location and number, stone clearance and ancillary
      procedures were compared. There were no significant differences between Group 1
      versus Group 2 for age (p > 0.05), gender (p > 0.05), stone site (p > 0.05) and
      stone size (p > 0.05). Stones with multiple locations were more frequent in Group
      1 (18.5%); however, the difference did not reach statistical significance between
      the two groups. Similarly, the frequency of multiple stones was also higher in
      Group 1 (29.6%). Stone site, diameter and gender were comparable in both groups.
      Stone-free rate of all patients was 84.6% after the first intervention. This rate
      increased to 98.1% after secondary procedures. Univariate analysis revealed that
      SFR after URS were low in patients who underwent previous intraureteral
      manipulations (Group 1:55.6% vs. Group 2:89.1%). SFR after the first intervention
      were related with stone size, location and number. Additionally, multiple
      logistic regression analysis indicated a relationship between previous
      intraureteral manipulations and initial stone clearance rates. Spontaneous
      passage of stone fragments after URS was associated with stone burden, location,
      number and previous intraureteral manipulations. Further multiple logistic
      regression analysis showed that only previous intraureteral manipulations were
      associated with the expulsion of the stones left for passage.

PMID- 21892748
TI  - Proteomic analyses of host and pathogen responses during bovine mastitis.
AB  - The pursuit of biomarkers for use as clinical screening tools, measures for early
      detection, disease monitoring, and as a means for assessing therapeutic responses
      has steadily evolved in human and veterinary medicine over the past two decades.
      Concurrently, advances in mass spectrometry have markedly expanded proteomic
      capabilities for biomarker discovery. While initial mass spectrometric biomarker
      discovery endeavors focused primarily on the detection of modulated proteins in
      human tissues and fluids, recent efforts have shifted to include proteomic
      analyses of biological samples from food animal species. Mastitis continues to
      garner attention in veterinary research due mainly to affiliated financial losses
      and food safety concerns over antimicrobial use, but also because there are only
      a limited number of efficacious mastitis treatment options. Accordingly,
      comparative proteomic analyses of bovine milk have emerged in recent years.
      Efforts to prevent agricultural-related food-borne illness have likewise fueled
      an interest in the proteomic evaluation of several prominent strains of bacteria,
      including common mastitis pathogens. The interest in establishing biomarkers of
      the host and pathogen responses during bovine mastitis stems largely from the
      need to better characterize mechanisms of the disease, to identify reliable
      biomarkers for use as measures of early detection and drug efficacy, and to
      uncover potentially novel targets for the development of alternative
      therapeutics. The following review focuses primarily on comparative proteomic
      analyses conducted on healthy versus mastitic bovine milk. However, a comparison
      of the host defense proteome of human and bovine milk and the proteomic analysis
      of common veterinary pathogens are likewise introduced.

PMID- 21892750
TI  - Angiogenesis in triple-negative adenoid cystic carcinomas of the breast.
AB  - We compared microvascular density (MVD), lymph vessel density (LVD), and the
      expression of hypoxia pathway-associated proteins between primary triple-negative
      adenoid cystic carcinoma of the breast (TN-ACC) and grade-matched triple-negative
      breast carcinomas of no special type (TNBC). Twelve TN-ACC and 15 TNBC were
      investigated immunohistochemically for CD31, podoplanin (D2-40), von Hippel
      Lindau protein (pVHL), and hypoxia-inducible factor-1alpha (HIF-1alpha) protein.
      All cases were lymph node negative (pN0). The study revealed a median MVD (CD31)
      of 34 vessels/mm(2) (mean +/- SD, 41.33 +/- 6.5/mm(2)) in the TN-ACC subgroup and
      a median of 55 microvessels (mean +/- SD, 54.9 +/- 6.3/mm(2)) in the TNBC
      subgroup. The median LVD (D2-40) was 10.5/mm(2) (mean +/- SD, 11.9 +/- 1.5/mm(2))
      in the TN-ACC subgroup and 15.0/mm(2) (mean +/- SD, 16.9 +/- 2.5/mm(2)) lymph
      vessels in the TNBC subgroup. The differences were not statistically significant
      (P = 0.93, P = 0.67, respectively). pVHL was detectable in all TN-ACCs whereas
      two cases of TNBC had less than 5% of the positive cells. HIF-1alpha protein
      expression was significantly higher in the tumor cell population than in adjacent
      normal cells in both subgroups (P = 0.009 for TNBC and P = 0.028 for TN-ACC,
      respectively), but there was no significant difference between the two tumor
      groups. Up-regulation of the hypoxia-induced signaling is seen in both TN-ACC and
      grade-matched TNBC. Despite its perceived low malignant potential, TN-ACC of the
      breast does not differ in the number of blood and lymphatic vessels in comparison
      with the grade-matched TNBC. The reported biologic differences between TN-ACC and
      TNBC do not appear to result from neoangiogenesis.

PMID- 21892751
TI  - The role of tumor hypoxia in MUC1-positive breast carcinomas.
AB  - Mucin 1 (MUC1) is a glycoprotein that is expressed on apical cell membranes in a
      variety of normal tissues. MUC1 is involved in cell signaling, inhibition of cell
      cell and cell matrix adhesion, apoptosis, proliferation, and transcription.
      Hypoxia is an important factor that promotes cancer metastasis and stimulates
      angiogenesis and tumor progression. Hypoxia inducible factor 1 (HIF-1alpha) and
      carbonic anhydrase IX (CAIX) are two molecules that are involved in this process.
      The role of hypoxia in MUC1+ invasive ductal breast carcinomas is not well
      established. In this study, the expression of MUC1 was correlated with the
      hypoxia-associated markers HIF-1alpha and CAIX, as well as several
      immunohistochemical markers and clinicopathologic features of prognostic
      significance in 243 invasive ductal carcinomas. MUC1 was overexpressed in 37.0%
      of patients and correlated with the expression of estrogen receptor (p = 0.0001),
      progesterone receptor (p = 0.0001), HIF-1alpha (p = 0.006), VEGF (p = 0.024), and
      p53 (p = 0.025). In breast cancer, MUC1 expression has been associated with
      increased degradation of inhibitor of NF-kappaB (IkappaBalpha), driving NF-kappaB
      to the nucleus and blocking apoptosis and promoting cell survival. We analyzed NF
      kappaB expression in MUC1+ breast carcinoma and found a very significant
      relationship between these proteins (p = 0.0001). Our findings indicate that MUC1
      may play a role in the regulation of hormone receptors by increasing the
      inactivation of p53 and targeting NF-kappaB to the nucleus. Our data also support
      the notion that activation of HIF-1alpha in MUC1+ breast carcinomas may modulate
      VEGF expression, allowing a metabolic adaptation to hypoxia.

PMID- 21892752
TI  - MTA1 expression correlates significantly with cigarette smoke in non-small cell
      lung cancer.
AB  - Metastasis tumor antigen 1 (MTA1), a novel candidate metastasis-associated gene,
      is known to increase the migration and invasion of various tumor cells in vitro.
      Expression of MTA1 has been shown to be closely correlated with aggressiveness in
      a variety of human cancers including non-small cell lung cancer (NSCLC).
      Cigarette smoke is the most established risk for lung carcinogenesis; however,
      its effects on the progression of NSCLC are still unclear. In this study, we
      investigated MTA1 expression and analyzed its association with cigarette smoke in
      NSCLC by immunohistochemistry. To gain a deeper insight into the molecular
      mechanism underlying the relation between MTA1 and cigarette smoke, we treated
      the NSCLC cell lines with cigarette smoke extract (CSE). MTA1 mRNA levels and
      proteins were detected in NSCLC cell lines via reverse transcriptase-polymerase
      chain reaction (RT-PCR) and western blot analysis. Matrigel invasion assay was
      performed to evaluate cell invasive ability with the treatment of CSE.
      Immunohistochemical analysis showed MTA1 expression in NSCLC (61/96, 63.5%) was
      higher than that in adjacent normal lung tissues (15/96, 15.6%; p < 0.05).
      Moreover, it was significantly associated with smoking history (p < 0.05). The
      results of RT-PCR and western blotting showed the upregulation of MTA1 after the
      treatment of CSE in NSCLC cell lines. Matrigel invasion assays showed that MTA1
      upregulation and cell invasion was accompanied with the treatment of CSE in the
      NSCLC cell lines. MTA1 expression correlated with cigarette smoke in NSCLC and
      suggested that it may play an important role in the smoked-related progress of
      NSCLC.

PMID- 21892753
TI  - Coronary artery calcium: utilization for primary prevention of CHD.
AB  - The rapidly accumulating data supporting coronary artery calcium (CAC) has
      necessitated multiple paradigm shifts in primary prevention: 1) CAC is the most
      powerful predictor of cardiac risk in the asymptomatic primary prevention
      population. 2) The most important role of risk factors may be to identify the
      modifiable targets of risk reduction in patients with risk already established by
      CAC. 3) "Normal cholesterol" values derived from population-based studies are not
      relevant for individual patients. 4) Measures of subclinical atherosclerosis (ie,
      serial CAC), rather than lipid values, define residual risk just as they define
      pretreatment risk. 5) Randomized controlled trials are not a prerequisite for
      implementation of CAC screening. 6) Trials evaluating lipid-treating drugs should
      exclude patients with 0 CAC. 7) CAC is the most cost-effective primary prevention
      approach.

PMID- 21892754
TI  - Clinical significance of CA125 and CA72-4 in gastric cancer with peritoneal
      dissemination.
AB  - BACKGROUND: Serum tumor markers have been shown to correlate with the clinical
      status of patients with advanced gastric cancer. However, the clinical
      significance of each tumor marker in patients with peritoneal dissemination has
      not been fully verified. METHODS: Four serum markers, carcinoembryonic antigen
      (CEA), carbohydrate antigen (CA) 19-9, CA125, and CA72-4, were periodically
      measured in 102 patients with peritoneal dissemination who received combination
      intravenous and intraperitoneal chemotherapy. The initial values at diagnosis and
      after treatment were analyzed in association with clinicopathological factors,
      response to chemotherapy, and overall survival. RESULTS: The sensitivities of
      CEA, CA19-9, CA125, and CA72-4 for peritoneal metastasis at the initial diagnosis
      were 19, 36, 46, and 45%, respectively. The CA125 level was significantly
      correlated with the degree of peritoneal dissemination and the existence of
      malignant ascites. Patients with ovarian metastasis showed significantly higher
      levels of CA72-4. The median survival time of patients with an elevated CA125
      level was significantly shorter than that of patients with a normal CA125 level
      (36.7 vs. 16.6 months, p < 0.001). Multivariate analysis showed that the degree
      of peritoneal metastasis and an elevated CA125 level were independent prognostic
      factors. Normalization of the CA125 level after 3 courses of chemotherapy was
      correlated with reduced ascites and improved survival. CONCLUSIONS: Serum CA125
      and CA72-4 are clinically useful markers in diagnosis, evaluating the efficacy of
      chemotherapy, and predicting the prognosis of patients with peritoneal
      dissemination. From an academic point of view, periodic measurements of these
      markers are warranted in gastric cancer patients with possible peritoneal
      dissemination.

PMID- 21892755
TI  - Development and characterization of intron-flanking EST-PCR markers in rubber
      tree (Hevea brasiliensis Muell. Arg.).
AB  - With a long-term goal of constructing a linkage map enriched with gene-specific
      markers in rubber tree (Hevea brasiliensis Muell. Arg.), we utilized rubber tree
      ESTs associated with tapping panel dryness (TPD) to develop intron-flanking PCR
      markers. After downloading and assembling the rubber tree ESTs associated with
      TPD, we predicted the exon/exon junction sites (E/E) by aligning rubber tree
      transcripts with the genomic sequences of castor bean (Ricinus communis L.).
      Based on the predicted E/E, the primers flanking intron(s) and no intron were
      designed. Compared with the markers designed by conventional method, the PCR
      success rate of the markers designed with the predicted E/E increased 28-30%,
      whereas the polymorphism rate of intron-flanking EST-PCR markers was
      approximately 3.43-fold increase. Therefore, the intron-flanking marker was more
      polymorphism-generating efficient than the markers designed by conventional
      methods. In addition, analyzing the polymorphic information content (PIC) among
      Hevea germplasm showed that the polymorphism of wild rubber tree accessions was
      higher than one of cultivated rubber tree clones and Hevea species. This study
      enriches the categories and numbers of molecular markers in rubber tree, and the
      markers developed in this research will have a wide application in DNA
      fingerprinting, marker-assisted selection and genetic mapping in rubber tree.
      This research also indicates that it is possible to develop intron-flanking EST
      PCR markers of rubber tree with castor bean genome as reference sequences, which
      provides new insights into developing intron-flanking EST-PCR markers for rubber
      tree or other plant species without genomic information.

PMID- 21892756
TI  - Three new megastigmanes from the leaves of Annona muricata.
AB  - Three new megastigmanes (1-3), named annoionols A and B (1, 2) and annoionoside
      (3), were isolated from the leaves of Annona muricata L. (Annonaceae) together
      with 14 known compounds (4-17). Among the known compounds, annoionol C (4) was
      isolated from a natural source for the first time. The structures of all
      compounds were elucidated by spectroscopic and chemical analyses.

PMID- 21892757
TI  - Omega-3 fatty acids in food and pharma: the enabling role of biotechnology.
AB  - Omega-3 fatty acid research, which began as an epidemiologic curiosity, has
      generated perhaps the strongest dataset for any nutrient in regard to
      cardiovascular disease risk reduction. Although once a relatively descriptive
      field, advances in analytic techniques have opened up the biochemistry of omega-3
      fatty acids and nutritional genomics in plants and man and have taken the field
      into the "omic" era. Despite this progress, fundamental questions remain
      unanswered, such as which fatty acid or metabolite thereof drives a given health
      benefit, how much of a given fatty acid should we consume, and how do we best
      source the requisite fatty acids? Of these questions, the ability to source omega
      3 fatty acids in order to meet dietary guidelines has become a practical concern.
      The advent of novel oils from plants and single cell organisms as enabled by
      biotechnology may provide a solution to this problem and in the process open up
      new uses for omega-3 fatty acids in dietary supplements and drugs.

PMID- 21892758
TI  - Potential mechanisms of progranulin-deficient FTLD.
AB  - Frontotemporal lobar dementia (FTLD) is the most common cause of dementia in
      patients younger than 60 years of age, and causes progressive neurodegeneration
      of the frontal and temporal lobes usually accompanied by devastating changes in
      language or behavior in affected individuals. Mutations in the progranulin (GRN)
      gene account for a significant fraction of familial FTLD, and in the vast
      majority of cases, these mutations lead to reduced expression of progranulin via
      nonsense-mediated mRNA decay. Progranulin is a secreted glycoprotein that
      regulates a diverse range of cellular functions including cell proliferation,
      cell migration, and inflammation. Recent fundamental discoveries about
      progranulin biology, including the findings that sortilin and tumor necrosis
      factor receptor (TNFR) are high affinity progranulin receptors, are beginning to
      shed light on the mechanism(s) by which progranulin deficiency causes FTLD. This
      review will explore how alterations in basic cellular functions due to PGRN
      deficiency, both intrinsic and extrinsic to neurons, might lead to the
      development of FTLD.

PMID- 21892759
TI  - Sarcomatous transformation in the McCune-Albright syndrome.
AB  - BACKGROUND: McCune-Albright syndrome is a relatively rare disease characterized
      by the trio of fibrous dysplasia, cafe-au-lait pigmentation, and endocrine
      disturbances. It predominantly affects females and may be associated with
      sarcomatous degeneration in 0.4% to 4% of the cases. CASE REPORT: This article
      reports on the case of a 24-year-old female patient who had presented a mass in
      the oral cavity for 30 days, probably originating from the left ramus of the
      mandible. She had a previous diagnosis of polyostotic fibrous dysplasia, along
      with cafe-au-lait spots and endocrine disorders, thus characterizing McCune
      Albright syndrome. Histopathological examination of a biopsy specimen revealed
      osteosarcoma of the mandible. The patient underwent chemotherapy and a surgical
      procedure for lesion resection. One year has now passed since the patient's
      operation, and the disease is under control. DISCUSSION: The patient presented
      sarcomatous degeneration in areas of fibrous dysplasia, consisting of mesenchymal
      cells that produced osteoid. Malignant degeneration is rare when it is not
      associated with McCune-Albright syndrome. There is no curative treatment for the
      syndrome. Attending physicians need to bring endocrine disorders under control,
      with surgical treatment in cases of significant deformities, as well as providing
      clinical and psychological care.

PMID- 21892760
TI  - Tau protein and beta-amyloid(1-42) CSF levels in different phenotypes of
      Parkinson's disease.
AB  - Parkinson's disease (PD) is a neurodegenerative disorder with highly
      heterogeneous clinical manifestations. This fact has prompted many attempts to
      divide PD patients into clinical subgroups. This could lead to a better
      recognition of pathogenesis, improving targeted treatment and the prognosis of PD
      patients. The aim of the present study was to obtain cerebrospinal fluid (CSF)
      samples in PD patients and to search for a relationship between neurodegenerative
      CSF markers (tau protein, beta-amyloid(1-42) and index tau protein/beta-amyloid(1
      42)) and the clinical subtypes. PD patients were divided into three subgroups:
      early disease onset (EDO), tremor-dominant PD (TD-PD), and non-tremor dominant PD
      (NT-PD) according to the previously published classification. Neurodegenerative
      markers in the CSF were assessed in these three groups of patients suffering from
      PD (EDO-17, TD-15, NT-16 patients) and in a control group (CG) of 19 patients
      suffering from non-degenerative neurological diseases and 18 patients with
      Alzheimer's disease (AD). The NT-PD patients were found to have significantly
      higher levels of CSF tau protein and index tau/beta than the control subjects and
      other Parkinsonian subgroups, but no significant differences in these markers
      were found between AD and NT-PD patients. In the context of more rapid clinical
      progression and more pronounced neuropathological changes in the NT-PD patient
      group, our results corroborate the opinion that CSF level of tau protein may be
      regarded as a potential laboratory marker of the presence and severity of
      neurodegeneration.

PMID- 21892761
TI  - Occurrence and sources of bromate in chlorinated tap drinking water in
      Metropolitan Manila, Philippines.
AB  - Significant levels of potentially carcinogenic bromate were measured in
      chlorinated tap drinking water in Metropolitan Manila, Philippines, using an
      optimized ion-chromatographic method. This method can quantify bromate in water
      down to 4.5 MUg l-1 by employing a postcolumn reaction with acidic fuchsin and
      subsequent spectrophotometric detection. The concentration of bromate in tap
      drinking water samples collected from 21 locations in cities and municipalities
      within the 9-month study period ranged from 7 to 138 MUg l-1. The average bromate
      concentration of all tap drinking water samples was 66 MUg l-1 (n = 567), almost
      seven times greater than the current regulatory limit in the country. The levels
      of bromate in other water types were also determined to identify the sources of
      bromate found in the distribution lines and to further uncover contaminated
      sites. The concentration of bromate in water sourced from two rivers and two
      water treatment plants ranged from 15 to 80 and 12 to 101 MUg l-1, respectively.
      Rainwater did not contribute bromate in rivers but decreased bromate level by
      dilution. Groundwater and wastewater samples showed bromate concentrations as
      high as 246 and 342 MUg l-1, respectively. Bromate presence in tap drinking water
      can be linked to pollution in natural water bodies and the practice of using
      hypochlorite chemicals in addition to gaseous chlorine for water disinfection.
      This study established the levels, occurrence, and possible sources of bromate in
      local drinking water supplies.

PMID- 21892762
TI  - Evaluation of naturally occurring radioactive materials (NORMs) in inorganic and
      organic oilfield scales from the Middle East.
AB  - The distribution of natural nuclide gamma-ray activities and their respective
      annual effective dose rates, produced by potassium-40 (40K), uranium-238 (238U),
      thorium-232 (232Th), and radium-226 (226Ra), were determined for 14 oilfield
      scale samples from the Middle East. Accumulated radioactive materials concentrate
      in tubing and surface equipment, and workers at equipment-cleaning facilities and
      naturally occurring radioactive materials (NORMs) disposal facilities are the
      population most at risk for exposure to NORM radiation. Gamma-spectra analysis
      indicated that photo-gamma lines represent the parents of 10 radioactive
      nuclides: 234Th, plutonium-239, actinium-228, 226Ra, lead-212 (212Pb), 214Pb,
      thallium-238 (208Tl), bismuth-212 (212Bi), 214Bi, and 40K. These nuclides
      represent the daughters of the natural radioactive series 238U and 232Th with 40K
      as well. The mean activity concentration of 238U, 232Th, and 40K were found to be
      25.8 +/- 11.6, 18.3 +/- 8.1, and 4487.2 +/- 2.5% Bq kg-1 (average values for 14
      samples), respectively. The annual effective dose rates and the absorbed doses in
      air, both indoor and outdoor, for the samples were obtained as well. The results
      can be used to assess the respective hazard on workers in the field and represent
      a basis for revisiting current engineering practices.

PMID- 21892763
TI  - Muscle invasion in oral tongue squamous cell carcinoma as a predictor of nodal
      status and local recurrence: just as effective as depth of invasion?
AB  - Tumor depth of invasion (DOI) is a histologic feature that consistently
      correlates with lymph node metastasis; however, there are many difficulties with
      accurately assessing DOI. The aim of this study was to identify a simpler and
      more reproducible method of determining DOI, by using skeletal muscle invasion as
      a surrogate marker of depth. Oral tongue squamous cell carcinoma  American Joint
      Committee on Cancer (AJCC) stage T1 cases were identified in the Emory University
      Department of Pathology database. 61 cases, with a minimum of 2 years of follow
      up, were included in the study. Cases were examined histologically to assess
      muscle invasion and DOI. The two methods of measurement were analyzed to
      determine the positive predictive value (PPV) of DOI or muscle invasion for both
      nodal disease and local recurrence. Cases with muscle invasion had a 23.3% PPV of
      occult lymph node metastasis. Cases with DOI of greater than 3 mm had a 29.7% PPV
      of occult lymph node metastasis. Cases with muscle invasion had a 43.7% PPV of
      local tumor recurrence. Cases with maximum DOI of greater than 3 mm had a 40.4%
      PPV of tumor recurrence. Although the PPV of muscle invasion in regards to nodal
      status was slightly less than DOI, it represents a more easily reproducible
      parameter which could guide surgeons in determining if the case warrants an
      elective neck dissection in a cN0 (clinically negative) neck. Interestingly, the
      PPV of local recurrence was higher with muscle invasion than DOI, and may
      represent an important indicator for extent of resection.

PMID- 21892764
TI  - Clinical pathologic conference case 6: infantile myofibroma.

PMID- 21892765
TI  - The high mitotic count detected by phospho-histone H3 immunostain does not alter
      the benign behavior of angiocentric glioma.
AB  - Angiocentric glioma (AG) has been formally codified in the revised 2007 WHO
      Classification of Tumours of the Central Nervous System. AGs characteristically
      exhibit mixed features of ependymal and diffuse astrocytic differentiation and
      low proliferation rates, with Ki-67 labeling indices ranging from less than 1 to
      5%. A single case with anaplastic recurrence and a labeling index of 10% has been
      reported. In the present study, we report a series of three AGs (Case 1: 4-year
      old girl at right frontal lobe; Case 2: 4-year-old boy at left frontal lobe; Case
      3: 9-year-old boy at right temporal lobe). Case 1 with elevated proliferation
      index (~10%) and increased mitotic activity (six mitoses per 10 high-power
      fields) on phospho-histone H3 (pHH3) immunostain at presentation, nonetheless,
      has shown protracted recurrence-free survival after 6 years of follow-up. So far,
      this is the first report for evaluating the mitotic activity in AGs using pHH3
      immunostain.

PMID- 21892766
TI  - Determination of bovine rotavirus G serotype by polymerase chain reaction.
AB  - A total of 113 diarrheic samples comprising of 68 buffalo calves and 45 cow
      calves were screened by RNA-PAGE for the detection of presence of rotavirus. RNA
      PAGE analysis of these samples revealed 11 (9.73%) was found positive for
      rotavirus. Out of 68 faecal samples of buffalo calves tested for viral
      gastroenteritis, 8 (11.76%) were found positive for rotavirus. Similarly, out of
      45 faecal samples of cattle calves tested for viral gastroenteritis, 3 (6.66%)
      was found positive for rotavirus. Rotavirus-positive samples represented long
      electropherotype. All RNA-PAGE-positive faecal samples for rotavirus subjected to
      RT-PCR for VP7 gene, ten samples yielded a specific product of 1,013 bp of VP7
      gene. All the PCR-positive samples of the present study were subjected to
      genotyping with primers for G6, G8 and G10 genotype. All positive samples showed
      G10 genotype. This indicates that G10 may be predominant genotype among bovine
      calves in Mumbai region in India.

PMID- 21892767
TI  - Coping with arthritis is experienced as a dynamic balancing process. A
      qualitative study.
AB  - The aim of this study was to investigate the process of coping in people living
      with chronic inflammatory arthritis. Semi-structured individual face-to-face
      interviews with 26 persons having rheumatoid arthritis, psoriatic arthritis or
      unspecified polyarthritis were performed. The informants were asked how they
      experienced to live with arthritis and how they coped with challenges due to the
      arthritis. The main finding was that the informants experienced the process of
      coping with arthritis as a dynamic, iterative, balancing process. They balanced
      between different states, entitled "go on as usual", "listen to the body",
      "adjustments" and "attitude towards life". The informants preferred to be in a
      "go on as usual" state as this was seen as normal life. However, disease
      fluctuations with pain, fatigue and stiffness disturbed the balance and made the
      informants "listen to the body", a state where they became aware of how the
      disease affected them, followed by the "adjustment" state. Adjustments were
      composed of different efforts to ease the arthritis influence and for regaining
      balance. The "attitude towards life" influenced the overall process of coping. A
      redefined view of what the informants considered to be normal life thus happened
      through longer periods of imbalance. The process of coping with arthritis was
      found to be a dynamic, iterative, balancing process where patients redefined what
      they considered as normal life through the course of the disease.

PMID- 21892769
TI  - SNP array-based whole genome homozygosity mapping as the first step to a
      molecular diagnosis in patients with Charcot-Marie-Tooth disease.
AB  - Considerable non-allelic heterogeneity for autosomal recessively inherited
      Charcot-Marie-Tooth (ARCMT) disease has challenged molecular testing and often
      requires a large amount of work in terms of DNA sequencing and data
      interpretation or remains unpractical. This study tested the value of SNP array
      based whole-genome homozygosity mapping as a first step in the molecular genetic
      diagnosis of sporadic or ARCMT in patients from inbred families or outbred
      populations with the ancestors originating from the same geographic area. Using
      10 K 2.0 and 250 K Nsp Affymetrix SNP arrays, 15 (63%) of 24 CMT patients
      received an accurate genetic diagnosis. We used our Java-based script eHoPASA CMT
      easy Homozygosity Profiling of SNP arrays for CMT patients to display the
      location of homozygous regions and their extent of marker count and base-pairs
      throughout the whole genome. CMT4C was the most common genetic subtype with
      mutations detected in SH3TC2, one (p.E632Kfs13X) appearing to be a novel founder
      mutation. A sporadic patient with severe CMT was homozygous for the c.250G > C
      (p.G84R) HSPB1 mutation which has previously been reported to cause autosomal
      dominant dHMN. Two distantly related CMT1 patients with early disease onset were
      found to carry a novel homozygous mutation in MFN2 (p.N131S). We conclude that
      SNP array-based homozygosity mapping is a fast, powerful, and economic tool to
      guide molecular genetic testing in ARCMT and in selected sporadic CMT patients.

PMID- 21892768
TI  - Cooperation of deregulated Notch signaling and Ras pathway in human
      hepatocarcinogenesis.
AB  - Aberrant Notch signaling and Ras pathway had been highlighted a potential role
      for in human cancers. Yet, relatively little was known about the roles of wild
      type Notch signaling and Ras in human hepatocarcinogenesis. The aim of this study
      was to investigate the roles of Ras-Notch signaling cooperation in hepatic cells
      transformation and proliferation. Hepatocellular carcinoma specimens from 25
      patients were analyzed for Notch-1, Ras and Late Simian Virus 40 Factor (LSF)
      expression using immunohistochemistry. Results showed that Notch-1(76%, 19/25, P
      < 0.0001), Ras (40%, 10/25, P < 0.01) and LSF (84%, 21/25, P < 0.0001) were
      significantly up-regulated in hepatocellular carcinoma compared with non-cancer
      samples. The correlations between the expression and the biological effects of
      Notch1 and Ras were analyzed by genetic and pharmacological methods.
      Constitutively active Notch1 alone failed to transform immortalized L02 cells in
      vivo, it synergized with the Ras pathway to promote hepatic cells transformation.
      However, their cooperation increased the levels of LSF mRNA and protein, which
      stimulates L02 cells proliferation. These results exhibited highly aggressive
      progression, suggesting that Notch-Ras cooperation maybe lead to poor prognosis.
      Thus, combining the inhibition of the two pathways provided an attractive avenue
      for therapeutic intervention to overcome this advanced disease.

PMID- 21892770
TI  - Preserved myocardial blood flow in the apical region involved in takotsubo
      cardiomyopathy by quantitative cardiac PET assessment.

PMID- 21892771
TI  - Lectin affinity chromatography of articular cartilage fibromodulin: Some
      molecules have keratan sulphate chains exclusively capped by alpha(2-3)-linked
      sialic acid.
AB  - Fibromodulin from bovine articular cartilage has been subjected to lectin
      affinity chromatography by Sambucus nigra lectin which binds alpha(2-6)- linked N
      acetylneuraminic acid, and the structure of the keratan sulphate in the binding
      and non-binding fractions examined by keratanase II digestion and subsequent high
      pH anion exchange chromatography. It has been confirmed that the keratan sulphate
      chains attached to fibromodulin isolated from bovine articular cartilage may have
      the chain terminating N-acetylneuraminic acid residue alpha(2-3)- or alpha(2-6)
      linked to the adjacent galactose residue. Although the abundance of alpha(2-6)
      linked N-acetylneuraminic acid (ca. 22%) is such that this could cap one of the
      four chains in almost all fibromodulin molecules, it was found that ca. 34% of
      the fibromodulin proteoglycan molecules from bovine articular cartilage were
      capped exclusively with alpha(2-3)-linked N-acetylneuraminic acid. The remainder
      of the fibromodulin proteoglycans, which bound to the lectin had a mixture of
      alpha(2-3)- and alpha(2-6)-linked N-acetylneuraminic acid capping structures. The
      keratan sulphates attached to fibromodulin molecules capped exclusively with
      alpha(2-3)- linked N-acetylneuraminic acid were found to have a higher level of
      galactose sulphation than those from fibromodulin with both alpha(2-3)- and
      alpha(2-6)-linked N-acetylneuraminic acid caps, which bound to the Sambucus nigra
      lectin. In addition, both pools contained chains of similar length (ca. 8-9
      disaccharides). Both also contained alpha(1-3)-linked fucose, showing that this
      feature does not co-distribute with alpha(2-6)-linked N-acetylneuraminic acid,
      although these two features are present only in mature articular cartilage. These
      data show that there are discrete populations of fibromodulin within articular
      cartilage, which may have differing impacts upon tissue processes.

PMID- 21892773
TI  - Screening, cultivation, and biocatalytic performance of Rhodococcus boritolerans
      FW815 with strong 2,2-dimethylcyclopropanecarbonitrile hydratase activity.
AB  - In this work, a mild, efficient bioconversion of 2,2
      dimethylcyclopropanecarbonitrile (DMCPCN) to 2,2-dimethylcyclopropanecarboxamide
      (DMCPCA) in distilled water system was developed. The isolate FW815 was screened
      using the enrichment culture technique, displaying strong DMCPCN hydratase
      activity, and was identified as Rhodococcus boritolerans based on morphological,
      physiological, biochemical tests and 16S rRNA gene sequencing. Cultivation
      outcomes indicated that R. boritolerans FW815 was a neutrophile, with a growth
      optimum of 28-32 degrees C; its DMCPCN hydratase belonged to the Fe-type family,
      and was most active at 38-42 degrees C, pH 7.0, with maximal activity of 4.51 *
      10(4) U g(-1) DCW. R. boritolerans FW815 was found to be DMCPCA amidase-negative,
      eliminating the contamination of dimethylcyclopropanecarboxylic acid. Moreover,
      it displayed high activity and acceptable reusability in the non-buffered
      distilled water system, comparable to those in pH 7.0 phosphate buffer (50.0 mmol
      l(-1)).

PMID- 21892772
TI  - Emerging roles of the SUMO pathway in development.
AB  - Sumoylation is a reversible post-translational modification that targets a
      variety of proteins mainly within the nucleus, but also in the plasma membrane
      and cytoplasm of the cell. It controls diverse cellular mechanisms such as
      subcellular localization, protein-protein interactions, or transcription factor
      activity. In recent years, the use of several developmental model systems has
      unraveled many critical functions for the sumoylation system in the early life of
      diverse species. In particular, detailed analyses of mutant organisms in both the
      components of the SUMO pathway and their targets have established the importance
      of the SUMO system in early developmental processes, such as cell division, cell
      lineage commitment, specification, and/or differentiation. In addition, an
      increasing number of developmental proteins, including transcription factors and
      epigenetic regulators, have been identified as sumoylation substrates.
      Sumoylation acts on these targets through various mechanisms. For example, this
      modification has been involved in converting a transcription factor from an
      activator to a repressor or in regulating the localization and/or stability of
      numerous transcription factors. This review will summarize current information on
      the function of sumoylation in embryonic development in different species from
      yeast to mammals.

PMID- 21892774
TI  - Transforaminal injection of corticosteroids for lumbar radiculopathy: systematic
      review and meta-analysis.
AB  - BACKGROUND: Transforaminal epidural injection of steroids is used to treat lumbar
      radicular pain. However, there are only a few well-designed randomized,
      controlled studies on the effectiveness of steroid injection. STUDY DESIGN:
      Hence, this study aims to assess the effectiveness of steroid injection to treat
      lumbar radicular pain using a meta-analysis of transforaminal epidural injection
      therapy for low back and lumbar radicular pain. The comparison was based on the
      mean difference in the Visual Analogue Score (VAS) and Oswestry Disability Index
      (ODI) from baseline to the specified followed up. METHODS: The available
      literature of lumbar transforaminal epidural injections in managing low back and
      radicular pain was reviewed. Data sources included relevant literature of the
      English language identified through searches of PubMed and EMBASE from 1966 to
      2009, and manual searches of the bibliographies of known primary and review
      articles. Finally, the search included the Current Controlled Trials Register and
      the Cochrane Database of Controlled Trials. RESULTS: The initial search
      identified 126 papers. After screening, five randomised controlled trials (RCTs)
      were studied for analysis and only three of these had followed-up patients
      systematically with pain and disability outcome scores to 3 months and of these,
      only one had follow up to 12 months. A total of 187 patients ('treatment group'
      receiving local anaesthetic/steroid injection) were compared with 181 patients
      ('control' group, receiving local anaesthetic only or saline injection).
      Improvement in pain (standardised mean difference in VAS 0.2 in favour of
      'treatment'; 95%CI: -0.41 to 0.00, p = 0.05, I squared 0%) but not disability
      (standardised mean difference in ODI 0; 95%CI: -0.21 to 0.20, p = 0.99, I squared
      0%) was observed between 'treatment' and 'control' groups; these differences were
      not significant. Additionally, the one study following patients to 12 months did
      not find any significant difference in VAS and ODI between treatment and control
      groups. CONCLUSION: The current meta-analysis shows that transforaminal epidural
      steroid injections, when appropriately performed, should result in an improvement
      in pain, but not disability. The three RCTs that followed patients to 3 months
      (and the single study to 12 months) have found no benefit by the addition of
      steroids. The limitations of this study include the paucity of the available
      literature.

PMID- 21892775
TI  - Arachnoid ossificans containing metaplastic hematopoietic marrow resulting in
      diffuse thoracic intrathecal cysts and severe myelopathy.
AB  - OBJECTIVE: To present a rare case of multiple compressive thoracic intradural
      cysts with pathologic arachnoid ossification, review the literature and present
      the surgical options. Few reports have identified the existence of arachnoid
      calcifications and intrathecal cysts causing progressive myelopathy. The
      literature regarding each of these pathologies is limited to case reports. Their
      clinical significance is not well studied, although known to cause neurologic
      sequelae. METHODS: An 81-year-old female clinically presents with rapidly
      progressive myelopathy. Pre-operative magnetic resonance imaging identified
      multiple compressive thoracic intrathecal cysts. Surgical exploration and
      decompression of these cysts identified calcified plaques within the arachnoid.
      Histopathologic examination revealed fibrocalcific tissue undergoing ossification
      with bone marrow elements. RESULTS: Due to progressive myelopathy, the thoracic
      cysts were decompressed and calcified plaques were excised, once identified intra
      operatively. CONCLUSIONS: On last examination, the patient's neurologic status
      had not improved, but had stabilized. The rate of neurologic improvement from
      excision and decompression is variable, but it may still be warranted in the face
      of progressive neurologic deficits.

PMID- 21892776
TI  - Very low mitochondrial diversity and genetic homogeneity in the starfish
      Echinaster sepositus along the Tunisian coast.

PMID- 21892777
TI  - Subtle deficits of cognitive theory of mind in unaffected first-degree relatives
      of schizophrenia patients.
AB  - Alterations of theory of mind (ToM) and empathy were implicated in the formation
      of psychotic experiences, and deficits in psychosocial functioning of
      schizophrenia patients. Inspired by concepts of neurocognitive endophenotypes,
      the existence of a distinct, potentially neurobiologically based social-cognitive
      vulnerability marker for schizophrenia is a matter of ongoing debate. The fact
      that previous research on social-cognitive deficits in individuals at risk
      yielded contradictory results may partly be due to an insufficient
      differentiation between qualitative aspects of ToM. Thirty-four unaffected first
      degree relatives of schizophrenia patients (21 parents, 8 siblings, 5 children;
      f/m: 30/4; mean age: 48.1 +/- 12.7 years) and 34 controls subjects (f/m: 25/9;
      mean age: 45.9 +/- 10.9 years) completed the 'Movie for the Assessment of Social
      Cognition'-a video-based ToM test-and an empathy questionnaire (Interpersonal
      Reactivity Index, IRI). Outcome parameters comprised (1) 'cognitive' versus
      'emotional' ToM, (2) error counts representing 'undermentalizing' versus
      'overmentalizing', (3) empathic abilities and (4) non-social neurocognition.
      MANCOVA showed impairments in cognitive but not emotional ToM in the relatives'
      group, when age, gender and neurocognition were controlled for. Relatives showed
      elevated error counts for 'undermentalizing' but not for 'overmentalizing'. No
      alterations were detected in self-rated dimensions of empathy. Of all measures of
      ToM and empathy, only the IRI subscale 'fantasy' was associated with measures of
      psychotic risk, i.e. a history of subclinical delusional ideation. The present
      study confirmed subtle deficits in cognitive, but not emotional ToM in first
      degree relatives of schizophrenia patients, which were not explained by global
      cognitive deficits. Findings corroborate the assumption of distinct social
      cognitive abilities as an intermediate phenotype for schizophrenia.

PMID- 21892778
TI  - The schizophrenia risk gene ZNF804A influences the antipsychotic response of
      positive schizophrenia symptoms.
AB  - Genetic factors determining the response to antipsychotic treatment in
      schizophrenia are poorly understood. A new schizophrenia susceptibility gene, the
      zinc-finger gene ZNF804A, has recently been identified. To assess the
      pharmacogenetic importance of this gene, we treated 144 schizophrenia patients
      and assessed the response of positive and negative symptoms by PANSS. Patients
      homozygous for the ZNF804A risk allele for schizophrenia (rs1344706 AA) showed
      poorer improvement of positive symptoms (7.35 +/- 0.46) compared to patients with
      a protective allele (9.41 +/- 0.71, P = 0.022). This provides further evidence
      that ZNF804A is of functional relevance to schizophrenia and indicates that
      ZNF804A may be a novel target for pharmacological interventions.

PMID- 21892779
TI  - Accuracy of stroke volume variation in predicting fluid responsiveness: a
      systematic review and meta-analysis.
AB  - PURPOSE: Stroke volume variation (SVV) appears to be a good predictor of fluid
      responsiveness in critically ill patients. However, a wide range of its
      predictive values has been reported in recent years. We therefore undertook a
      systematic review and meta-analysis of clinical trials that investigated the
      diagnostic value of SVV in predicting fluid responsiveness. METHODS: Clinical
      investigations were identified from several sources, including MEDLINE, EMBASE,
      WANFANG, and CENTRAL. Original articles investigating the diagnostic value of SVV
      in predicting fluid responsiveness were considered to be eligible. Participants
      included critically ill patients in the intensive care unit (ICU) or operating
      room (OR) who require hemodynamic monitoring. RESULTS: A total of 568 patients
      from 23 studies were included in our final analysis. Baseline SVV was correlated
      to fluid responsiveness with a pooled correlation coefficient of 0.718. Across
      all settings, we found a diagnostic odds ratio of 18.4 for SVV to predict fluid
      responsiveness at a sensitivity of 0.81 and specificity of 0.80. The SVV was of
      diagnostic value for fluid responsiveness in OR or ICU patients monitored with
      the PiCCO or the FloTrac/Vigileo system, and in patients ventilated with tidal
      volume greater than 8 ml/kg. CONCLUSIONS: SVV is of diagnostic value in
      predicting fluid responsiveness in various settings.

PMID- 21892781
TI  - Chemoresistance to temozolomide in human glioma cell line U251 is associated with
      increased activity of O6-methylguanine-DNA methyltransferase and can be overcome
      by metronomic temozolomide regimen.
AB  - Temozolomide (TMZ) is a novel cytotoxic alkylating agent for chemotherapy of
      malignant gliomas. However, intrinsic or acquired resistance to TMZ often defines
      poor efficacy of chemotherapy in malignant gliomas. A growing number of studies
      indicate that expression of O(6)-methylguanine-DNA methyltransferase (MGMT) is
      one of the principal mechanisms responsible for this chemoresistance. In the
      present study, we evaluated the relationship between expression of MGMT and
      resistance to TMZ. We generated a TMZ-resistant cell line, U251/TR, by stepwise
      (8 months) exposure of parental U251 cells to TMZ. The resistance to TMZ was
      quantified using SRB assay. MGMT expression was evaluated at mRNA (RT-PCR) and
      protein (Western blot) levels. U251/TR cells showed increased (~ sevenfold)
      resistance to TMZ. The MGMT expression (both mRNA and protein) was significantly
      (P < 0.01) increased in U251/TR cells compared with parental U251 cells. Further,
      MGMT expression fluctuated during exposure of U251/TR cells to TMZ. The
      resistance of U251/TR cells to TMZ could be overcome by application of elevated
      doses of TMZ when MGMT expression was at the lowest level. In conclusion, our
      results demonstrate that the primary mechanism responsible for resistance of
      U251/TR cells to TMZ is associated with increased expression of MGMT. Resistance
      of malignant gliomas to TMZ can be overcome by synchronizing metronomic TMZ
      regimen with MGMT expression.

PMID- 21892780
TI  - Models for anti-tumor activity of bisphosphonates using refined topochemical
      descriptors.
AB  - An in silico approach comprising of decision tree (DT), random forest (RF) and
      moving average analysis (MAA) was successfully employed for development of models
      for prediction of anti-tumor activity of bisphosphonates. A dataset consisting of
      65 analogues of both nitrogen-containing and non-nitrogen-containing
      bisphosphonates was selected for the present study. Four refinements of eccentric
      distance sum topochemical index termed as augmented eccentric distance sum
      topochemical indices 1-4 [formula: see text] have been proposed so as to
      significantly augment discriminating power. Proposed topological indices (TIs)
      along with the exiting TIs (>1,400) were subsequently utilized for development of
      models for prediction of anti-tumor activity of bisphosphonates. A total of 43
      descriptors of diverse nature, from a large pool of molecular descriptors,
      calculated through E-Dragon software (version 1.0) and an in-house computer
      program were selected for development of suitable models by employing DT, RF and
      MAA. DT identified two TIs as most important and classified the analogues of the
      dataset with an accuracy of 97% in training set and 90.7% in tenfold cross
      validated set. Random forest correctly classified the analogues with an accuracy
      of 89.2%. Four independent models developed through MAA predicted the activity of
      analogues of the dataset with an accuracy of 87.6% to 89%. The statistical
      significance of proposed models was assessed through intercorrelation analysis,
      specificity, sensitivity and Matthew's correlation coefficient. The proposed
      models offer a vast potential for providing lead structures for development of
      potent anti-tumor agents for treatment of cancer that has spread to the bone.

PMID- 21892782
TI  - Low-intensity international normalized ratio (INR) oral anticoagulant therapy in
      Chinese patients with mechanical heart valve prostheses.
AB  - The purpose of this study was to define the optimal international normalized
      ratio (INR) intensity of oral anticoagulant therapy in Chinese patients with
      valve replacement surgery. We studied 1,658 patients who underwent mechanical
      valve replacement in Beijing Anzhen Hospital; the focus of the study was on
      correlation between intensity of anticoagulant therapy and
      thromboembolism/hemorrhage complications. We further followed up 1,508 patients
      for 46 +/- 16 months (range 1-61 months). Average INR was 2.13 +/- 0.56, and
      warfarin dose was 3.09 +/- 0.85 mg/day. The incidence rate of anticoagulation
      related thromboembolism was 1.17 per 100 patient-years (%/pt-y), and the
      incidence rate of anticoagulation-related hemorrhage was 2.02%/pt-y. The
      incidence rate of total complications (i.e., combined thromboembolism and
      hemorrhages) was 3.24%/pt-y. The rate of total complications in group on INR 1.3
      2.3 (aortic valve replacement: 1.3-1.8; mitral valve replacement and double valve
      replacement: 1.8-2.3) was the lowest among all anticoagulant therapy regimens
      followed. In conclusion, the relatively low anticoagulant strategy presented
      above efficiently prevents thrombosis and hemorrhage complications.

PMID- 21892783
TI  - Effects of divided attention on swallowing in healthy participants.
AB  - Swallowing impairments are treated mostly behaviorally. It is requisite to
      understand the relationship of cognition, specifically attention, with swallowing
      since so many swallowing impairments occur concomitantly with cognitive
      disorders. This study examined the hypothesis that attentional resources are
      required during swallowing. The approach involved a dual-task, reaction time (RT)
      paradigm in ten healthy, nonimpaired participants. Baseline measures were
      obtained of the duration of the anticipatory phase and of the oropharyngeal phase
      of swallowing and the RTs to nonword auditory stimuli. A dual-task then required
      participants to swallow 5 ml of water from an 8-oz. cup while listening for a
      target nonword presented auditorily during the anticipatory or the oropharyngeal
      phase. Target stimuli were randomized across baseline and dual-task trials.
      Duration of the anticipatory phase and of the oropharyngeal phase of swallowing
      and duration of the RT baseline trial and of the dual-task trial were determined.
      Results showed a statistically significant increase in speed of the anticipatory
      phase, relative to the oropharyngeal phase, for swallowing during the dual-task.
      RTs were slowed for both the anticipatory and the oropharyngeal phase during the
      dual-task, although neither of these was statistically significant. Clinical
      implications of these data suggest that disruptive stimuli in the environment to
      nonimpaired individuals may alter feeding but have little effect on the
      oropharyngeal swallow.

PMID- 21892784
TI  - LC-PUFA biosynthesis in rainbow trout is substrate limited: use of the whole body
      fatty acid balance method and different 18:3n-3/18:2n-6 ratios.
AB  - Five experimental diets with constant total C(18) PUFA and varying 18:3n-3/18:2n
      6 ratios were fed to rainbow trout over an entire production cycle. The whole
      body fatty acid balance method demonstrated a clear trend of progressively
      reduced fatty acid bioconversion activity along the n-3 and n-6 pathways, up to
      the production of 20:5n-3 and 20:4n-6, respectively. This suggests that the
      pathway exhibits a "funnel like" progression of activity rather than the
      existence of a single rate limiting step. The production of 22:5n-3 and 22:6n-3
      was more active than that of 20:5n-3. However, despite this trend in reduced
      apparent in vivo net enzyme activity, the efficiency of the various bioconversion
      steps (measured as % of bioconverted substrate) confirmed an opposing trend. A
      3.2-fold higher Delta-6 desaturase affinity towards 18:3n-3 over 18:2n-6 and an 8
      fold greater Delta-5 desaturase affinity towards 20:4n-3 over 20:3n-6 were
      recorded. The main results of the study were that (1) rainbow trout are quite
      efficient at bioconverting 18:3n-3 to 22:6n-3, and (2) the LC-PUFA biosynthetic
      pathway is substrate limited. Fillet n-3 LC-PUFA concentrations increased with
      the increasing dietary supply of 18:3n-3. Despite an almost identical dietary
      supply of n-3 LC-PUFA, originating from the fish meal fraction of the diets, the
      fillets of trout fed the diet richest in 18:3n-3 were 2-fold higher in n-3 LC
      PUFA than fish fed low 18:3n-3 diets. Nevertheless, fillets of trout fed a fish
      oil control diet contained more than double the amount of n-3 LC-PUFA compared to
      fish fed the diets richest in 18:3n-3.

PMID- 21892785
TI  - Therapeutic options for acute cough due to upper respiratory infections in
      children.
AB  - Cough due to upper respiratory tract infections (URIs) is one of the most
      frequent complaints encountered by pediatric health-care providers, and one of
      the most disruptive symptoms for children and families. Despite the frequency of
      URIs, there is limited evidence to support the few therapeutic agents currently
      available in the United States (US) to treat acute cough due to URI. Published,
      well-designed, contemporary research supporting the efficacy of narcotics
      (codeine, hydrocodone) and US Food and Drug Administration (FDA)-approved over
      the-counter (OTC) oral antitussives and expectorants (dextromethorphan,
      diphenhydramine, chlophedianol, and guaifenesin) is absent for URI-associated
      pediatric cough. Alternatively, honey and topically applied vapor rubs may be
      effective antitussives.

PMID- 21892786
TI  - Characterization of new Alternaria alternata--specific rat monoclonal antibodies.
AB  - In this study, three different rat hybridoma cell lines secreting monoclonal
      antibodies (mAbs) recognizing the spores from Alternaria alternata, a plant
      pathogenic fungus, contaminant of food products and important cause of both
      allergic rhinitis and asthma, have been characterized. These three mAbs are all
      of IgM isotype. Two antibodies, A1 and F10, were cross-reactive antibodies
      recognizing spores from Alternaria, Cladosporium, Penicillium, Aspergillus and
      Stachybotrys genera, but not the yeasts Saccharomyces cerevisiae or Candida
      albicans. Competitive and sandwich assays demonstrated that these two mAbs were
      directed against the same or very close repetitive(s) epitope(s). A1-based
      sandwich ELISA efficiently detected this epitope in various mould (but not yeast)
      soluble extracts prepared from strains grown in the laboratory. Moreover, this A1
      based sandwich ELISA detected its cognate epitope in air and dust samples
      obtained from dwellings. The third antibody, E5, recognized only the spores of
      Alternaria and the phylogenetically very close Ulocladium botrytis. This E5
      antibody is directed against a repetitive epitope found in Alternaria and
      Ulocladium laboratory extracts and can be used in a sandwich assay for the
      quantification of these moulds. Therefore, E5 antibody is a promising tool for
      the development of Alternaria-Ulocladium-specific immunoassays, while A1 and F10
      could be interesting tools for the quantification of the total mould biomass.

PMID- 21892788
TI  - Three-dimensional in vivo motion analysis of normal knees using single-plane
      fluoroscopy.
AB  - BACKGROUND: Analysis of the movement of anatomically defined reference axes at
      the femoral condyles relative to the tibia is appropriate for evaluating knee
      kinematics. However, such parameters have been previously employed only in
      studies utilizing stop-motion techniques. The purpose of this study was to
      evaluate in vivo dynamic kinematics for full range of motion in normal knees
      using the three-dimensional to two-dimensional registration technique and to
      compare them with previously reported normal knee kinematics obtained via stop
      motion techniques. METHODS: Dynamic motion of the right knee was analyzed in 20
      healthy volunteers (10 female, 10 male; mean age 37.2 years). Knee motion was
      observed when subjects squatted from standing with the knee fully extended to
      maximum flexion. We determined the following parameters: (1) changes to angles of
      the geometric center axis (GCA) on the tibial axial plane (rotation angle); (2)
      anteroposterior translations of the medial and lateral ends of the GCA; and (3)
      motion patterns in each phase during knee flexion. RESULTS: All subjects
      exhibited femoral external rotation (26.1 degrees ) relative to the tibia
      throughout knee flexion. The medial femoral condyle demonstrated anterior
      translation (5.5 mm) from full extension to 100 degrees  flexion, and
      demonstrated posterior translation (3.9 mm) after 100 degrees , while the lateral
      femoral condyle demonstrated consistent posterior translation (15.6 mm)
      throughout knee flexion. All subjects showed medial pivot motion from full
      extension to nearly 120 degrees  flexion. From 120 degrees  flexion, bicondylar
      rollback motion was observed. DISCUSSION: Although the behavior of the medial
      femoral condyle in our analysis differed somewhat from that seen in previous
      cadaver studies, the results obtained using dynamic analysis were generally
      equivalent to those obtained in previous studies employing stop-motion
      techniques. These results provide control data for future dynamic kinematic
      analyses of pathological knees.

PMID- 21892787
TI  - Influence of hyaluronic acid on bacterial and fungal species, including
      clinically relevant opportunistic pathogens.
AB  - Hyaluronic acid (HA) has several clinical applications (aesthetic surgery,
      dermatology, orthopaedics and ophtalmology). Following recent evidence,
      suggesting antimicrobial and antiviral properties for HA, we investigated its
      effects on 15 ATCC strains, representative of clinically relevant bacterial and
      fungal species. The in vitro system employed allowed to assess optical density of
      broth cultures as a measure of microbial load in a time-dependent manner. The
      results showed that different microbial species and, sometimes, different strains
      belonging to the same species, are differently affected by HA. In particular,
      staphylococci, enterococci, Streptococcus mutans, two Escherichia coli strains,
      Pseudomonas aeruginosa, Candida glabrata and C. parapsilosis displayed a HA dose
      dependent growth inhibition; no HA effects were detected in E. coli ATCC 13768
      and C. albicans; S. sanguinis was favoured by the highest HA dose. Therefore, the
      influence of HA on bacteria and fungi warrants further studies aimed at better
      establishing its relevance in clinical applications.

PMID- 21892789
TI  - The 800-nm diode laser irradiation induces skin collagen synthesis by stimulating
      TGF-beta/Smad signaling pathway.
AB  - The 800-nm diode laser is used clinically for hair removal and leg vein
      clearance. However, the effects of the laser on skin collagen synthesis have not
      been established. This study aims to research whether the 800-nm laser can be
      used for non-ablative rejuvenation and its possible mechanism by using an animal
      model. Eight 2-month-old rats were irradiated with the 800-nm diode laser at 20,
      40, and 60 J/cm(2), respectively. Skin samples were taken for histological study
      and dermal thickness measurement at day 30 after laser irradiation. The
      expression of procollagen type I, III, IV, transforming growth factor-beta (TGF
      beta), Smad2, 3, 4, and phosphorylated-Smad2, 3 in the rat skin was analyzed 24 h
      after completing all laser treatments by using RT-PCR and Western blot.
      Immunohistochemistry was performed to evaluate the content of type I collagen in
      the skin at day 30 after laser irradiation. The 800-nm diode laser treatments
      markedly improved the histological structure and increased dermal thickness
      compared to the non-irradiated controls. Laser irradiation at 40 J/cm(2)
      significantly up-regulated the expression of procollagen type I and IV, TGF-beta
      and Smad2, 3, 4. The p-Smad2 and p-Smad3 levels were also enhanced in the laser
      irradiated skin. The 800-nm laser is effective in improving skin structure and
      inducing skin new collagen expression. New collagen synthesis induced by the 800
      nm laser was mediated by TGF-beta/Smad signaling pathway. Thus, it seemed that
      the 800-nm laser could be used for non-ablative rejuvenation in the future.

PMID- 21892790
TI  - Response of dietary substitution of fishmeal with various protein sources on
      growth, body composition and blood chemistry of olive flounder (Paralichthys
      olivaceus, Temminck & Schlegel, 1846).
AB  - Animal and/or plant protein sources substituting fishmeal in the diets keep being
      developed due to its high price. The purpose of this study is to determine
      response of dietary substitution of fishmeal with silkworm pupae meal, promate
      meal(r), meat and bone meal and/or their combination on the performance of
      juvenile olive flounder. A 60% fish meal was used as the main protein source,
      used as the control (Con) diet. The 10 and 20% fishmeal were substituted with
      silkworm pupae meal and meat and bone meal, referred to as the SPM10, SPM20,
      MBM10 and MBM20 diets, respectively. And the 10, 20 and 40% fishmeal were
      substituted with promate meal(r), referred to as the PM10, PM20 and PM40 diets,
      respectively. Finally, the 10 and 20% fishmeal were substituted with combined
      silkworm pupae meal and promate meal(r), refereed to as the SPM + PM10 and SPM +
      PM20 diets, respectively. Weight gain and specific growth rate of fish fed the
      MBM10 diet were higher than those of fish fed the Con, SPM20, PM20, PM40 and SPM
      + PM20 diets. Feed efficiency ratio of fish fed the SPM10, MBM10, MBM20, PM10 and
      SPM + PM10 diets was higher than that of fish fed the SPM + PM20 and PM40 diets.
      Protein efficiency ratio of fish fed the MBM10 and MBM20 diets was higher than
      that of fish fed the SPM20, PM20, PM40 and SPM + PM20 diets. In conclusion,
      dietary substitution of fishmeal with 10% SPM, 20% MBM, 10% PM and 10% SPM + PM
      could be made.

PMID- 21892791
TI  - Recoding preventive exposures to get valid measures of interaction on an additive
      scale.

PMID- 21892792
TI  - Differential gene expression analysis in Enchytraeus albidus exposed to natural
      and chemical stressors at different exposure periods.
AB  - The soil oligochaete Enchytraeus albidus is a standard test organism used in
      biological testing for Environmental Risk Assessment (ERA). Although effects are
      known at acute and chronic level through survival, reproduction and avoidance
      behaviour endpoints, very little is known at the sub-cellular and molecular
      levels. In this study, the effects of soil properties (clay, organic matter and
      pH) and of the chemicals copper and phenmedipham were studied on E. albidus gene
      expression, during exposure periods of 2, 4 and 21 days, using DNA microarrays
      based on a normalised cDNA library for this test species (Amorim et al. 2011).
      The main objectives of this study were: (1) to assess changes in gene expression
      of E. albidus over time, and (2) to identify molecular markers for natural and
      chemical exposures. Results showed an influence of exposure time on gene
      expression. Transcriptional responses to phenmedipham were seen at 2 days while
      the responses to copper and the different soils were more pronounced at 4 days of
      exposure. Some genes were differentially expressed in a stress specific manner
      and, in general, the responses were related with effects in the energy metabolism
      and cell growth.

PMID- 21892793
TI  - Progress in cell grafting therapy for temporal lobe epilepsy.
AB  - Temporal lobe epilepsy (TLE), exemplified by complex partial seizures, is
      recognized in ~30% of epileptic patients. Seizures in TLE are associated with
      cognitive dysfunction and are resistant to antiepileptic drug therapy in ~35% of
      patients. Although surgical resection of the hippocampus bestows improved seizure
      regulation in most cases of intractable TLE, this choice can cause lasting
      cognitive deficiency and reliance on antiepileptic drugs. Thus, alternative
      therapies that are proficient in both containing the spontaneous recurrent
      seizures and reversing the cognitive dysfunction are needed. The cell
      transplantation approach is promising in serving as an adept alternate therapy
      for TLE, because this strategy has shown the capability to curtail
      epileptogenesis when used soon after an initial precipitating brain injury, and
      to restrain spontaneous recurrent seizures and improve cognitive function when
      utilized after the occurrence of TLE. Nonetheless, this treatment needs further
      advancement and rigorous evaluation in animal prototypes of chronic TLE before
      the conceivable clinical use. It is especially vital to gauge the efficacy of
      distinct donor cell types, such as the hippocampal precursor cells, gamma
      aminobutyric acid-ergic progenitors, and neural stem cells derived from diverse
      human sources (including the embryonic stem cells and induced pluripotent stem
      cells) for longstanding seizure suppression using continuous
      electroencephalographic recordings for prolonged periods. Additionally, the
      identification of the mechanisms underlying the graft-mediated seizure
      suppression and improved cognitive function, and the development of apt grafting
      strategies that enhance the anti-seizure and pro-cognitive effects of grafts will
      be necessary. The goal of this review is to evaluate the progress made hitherto
      in this area and to discuss the prospect for cell-based therapy for TLE.

PMID- 21892794
TI  - Cys-Ph-TAHA: a lanthanide binding tag for RDC and PCS enhanced protein NMR.
AB  - Here we present Cys-Ph-TAHA, a new nonadentate lanthanide tag for the
      paramagnetic labelling of proteins. The tag can be easily synthesized and is
      stereochemically homogenous over a wide range of temperatures, yielding NMR
      spectra with a single set of peaks. Bound to ubiquitin, it induced large residual
      dipolar couplings and pseudocontact shifts that could be measured easily and
      agreed very well with the protein structure. We show that Cys-Ph-TAHA can be used
      to label large proteins that are biochemically challenging such as the Lac
      repressor in a 90 kDa ternary complex with DNA and inducer.

PMID- 21892795
TI  - Complicated grief and need for professional support in family caregivers of
      cancer patients in palliative care: a longitudinal cohort study.
AB  - OBJECTIVES: There is little research on complicated grief (CG) in family
      caregivers in palliative care. The aim of the study was to assess the levels of
      complicated grief and depression in family caregivers after the death of a
      relative with cancer, to identify their need for support, to compare the
      palliative team staff's risk assessment of the relatives' grief reaction with
      measured levels of CG and depression, and to assess the use of bereavement
      support. METHODS: All 114 eligible family caregivers to deceased patients treated
      in a palliative care unit in the year 2006 were asked to participate in the
      study, and 87 (77%) accepted. The participants completed a postal questionnaire
      2, 6, 13, and 18 months after the loss measuring complicated grief (Inventory of
      Complicated Grief, Revised), depression (Beck's Depression Inventory II), and
      their use of bereavement services. The palliative team staff completed a form 1
      month post-loss with their clinical risk assessment of the family caregivers'
      levels of complicated grief and need for support. RESULTS: The prevalence of
      moderate to severe depression and CG was 15% and 40%, respectively, at 6 months
      post-loss. Professional risk assessment showed a sensitivity of 55% for CG and of
      27% for depression and a specificity of 86% for depression and 63% for CG. The
      positive predictive value was 27% for depression and 21% for CG. Use of
      bereavement services was observed in 36% of the cases at 6 months after the loss.
      The proportion of bereaved with CG or depression at 6 months who had received
      bereavement services was 47% and 64%, respectively. CONCLUSIONS: The results
      suggest that a substantial number of family caregivers of diseased palliative
      care patients are at risk of developing CG and depression following their loss.
      While early identification of those at risk of developing CG could be helpful,
      the risk assessment of professionals may lack in precision. The results indicate
      that bereavement services could be utilized in a more targeted and perhaps more
      efficient manner. Guidelines for bereavement planning in palliative care are
      indicated.

PMID- 21892796
TI  - An unusual case of membranous nephropathy associated with an ovarian tumor.
AB  - Secondary membranous nephropathy (MN) associated with malignancy is not uncommon
      in adults, but it is rare in children. We report a 6-year-old girl who developed
      nephrotic-range proteinuria following diagnosis of a Sertoli-Leydig ovarian
      tumor. A renal biopsy was performed, which led to the diagnosis of MN. The
      patient maintained normal renal function and gradually showed improvement in
      proteinuria over several months without the use of corticosteroids or angiotensin
      converting enzyme inhibitors. Our case highlights the importance of performing
      screening urinalyses in children with tumors to recognize the presence of
      clinically significant, but potentially asymptomatic kidney disease.

PMID- 21892799
TI  - Familial occipital neuralgia with sporadic NIN: a reply.

PMID- 21892800
TI  - Familial occipital neuralgia with sporadic nervus intermedius neuralgia (NIN).

PMID- 21892801
TI  - [Promising approaches of translational research in head and neck cancer].

PMID- 21892802
TI  - [Anesthetic management in laryngotracheal surgery. High-frequency jet ventilation
      as strategy for ventilation during general anesthesia].
AB  - During surgical procedures of the upper respiratory tract anesthesiologists and
      surgeons are in a kind of competition situation because of the close spatial
      relationship between the airway of the patient and the surgical area. Especially
      in laryngeal surgery the use of high-frequency jet ventilation (HFJV) offers an
      alternative to the endotracheal tube. During HFJV the ventilation gas is
      intermittently administered by an injector with a high frequency into the airway
      which is open to the outside. Exhalation occurs passively in the area nearby the
      wall of the airway cross-section. According to the availability of the technique
      and the indications jet ventilation can be implemented in an infraglottic,
      supraglottic, transtracheal or transluminal manner. To exert influence on gas
      exchange of the patient the respiratory rate, driving pressure, oxygen
      concentration and inspiration time can be changed according to the needs. Severe
      tracheal stenosis, risk of excessive bleeding during the procedure, patients at
      risk for aspiration and exacerbation of lung diseases are depicted as
      contraindications for HFJV. Complications under HFJV are rare despite the limited
      conditions for monitoring gas exchange and mechanics of ventilation in contrast
      to conventional ventilation. A particular challenge for the anesthesiologist is
      the use of HFJV during laryngeal laser surgery.

PMID- 21892803
TI  - [Hyponatremia--should it be ignored or diagnosed?--Case 8/2011].
AB  - HISTORY, CLINICAL FINDINGS: A 72-year-old dehydrated female was admitted to our
      emergency department. She presented with a decreased level of consciousness and
      had experienced a fall. Her medication included hydrochlorothiazide and
      amiloride. DIAGNOSTIC: Laboratory findings showed a severe hyponatremia with a
      serum sodium concentration of 107 mmol/l and a reduced serum osmolality. Urine
      sodium and potassium excretion were > 30 mmol/l. A CT scan of the head did not
      show any signs of trauma. DIAGNOSIS, THERAPY AND CLINICAL COURSE: Using a
      diagnostic algorithm, the diagnosis of a hypotonic hypovolemic hyponatremia due
      to the intake of diuretics was confirmed. By intravenous infusion of
      physiological sodium chloride solution and cessation of diuretics, serum sodium
      concentration was raised gradually. Hereby, the patient's state of consciousness
      completely normalized. CONCLUSIONS: Hyponatremia represents the most frequent
      electrolyte disturbance of hospitalized patients. It correlates with neurological
      deficits, proneness to falling and intrahospital mortality. Due to diagnostic
      insecurity of many physicians, the finding of a hyponatremia is often ignored or
      misclassified. Standardized approaches using diagnostic algorithms improve
      diagnostic accuracy. The here presented algorithm is based on only few
      parameters: serum and urine osmolality, urine sodium and potassium. Besides
      gradual raise of serum sodium, therapy of the underlying cause is essential, for
      example cessation of diuretics. For patients with syndrome of inadequate
      secretion of antidiuretic hormone (SIADH; hypotonic isovolemic hyponatremia),
      selective arginin-vasopressin-receptor 2-antagonists (vaptans) are a new
      therapeutic option. However, due to high costs, we only see an indication for
      patients with SIADH who are not able to consequently comply with fluid
      restriction.

PMID- 21892804
TI  - The influence of nutrient supply and cell density on the growth and survival of
      intervertebral disc cells in 3D culture.
AB  - The adult human intervertebral disc (IVD) is normally avascular. Changes to the
      extracellular matrix in degenerative disc disease may promote vascularisation and
      subsequently alter cell nutrition and disc homeostasis. This study examines the
      influence of cell density and the presence of glucose and serum on the
      proliferation and survival of IVD cells in 3D culture. Bovine nucleus pulposus
      (NP) cells were seeded at a range of cell densities (1.25 * 10(5)-10(6) cells/mL)
      and cultured in alginate beads under standard culture conditions (with 3.15 g/L
      glucose and 10 % serum), or without glucose and/or 20% serum. Cell proliferation,
      apoptosis and cell senescence were examined after 8 days in culture. Under
      standard culture conditions, NP cell proliferation and cluster formation was
      inversely related to cell seeding density, whilst the number of apoptotic cells
      and enucleated "ghost" cells was positively correlated to cell seeding density.
      Increasing serum levels from 10% to 20% was associated with increased cluster
      size and also an increased prevalence of apoptotic cells within clusters.
      Omitting glucose produced even larger clusters and also more apoptotic and
      senescent cells. These studies demonstrate that NP cell growth and survival are
      influenced both by cell density and the availability of serum or nutrients, such
      as glucose. The observation of clustered, senescent, apoptotic or "ghost" cells
      in vitro suggests that environmental factors may influence the formation of these
      phenotypes that have been previously reported in vivo. Hence this study has
      implications for both our understanding of degenerative disc disease and also
      cell-based therapy using cells cultured in vitro.

PMID- 21892806
TI  - The effect of synthetic octacalcium phosphate in a collagen scaffold on the
      osteogenicity of mesenchymal stem cells.
AB  - Although the efficacy of the in vivo osteogenic capabilities of synthetic
      octacalcium phosphate (OCP) crystal implantation can be explained through its
      stimulatory capacity for the differentiation of the host osteoblastic cell
      lineage, direct evidence that OCP supports bone regeneration by osteogenic cells
      in vivo has not been shown. Mesenchymal stem cells (MSCs) isolated from 4-week
      old male Wistar rat long bones were pre-incubated in osteogenic or maintenance
      medium in the presence or absence of basic fibroblast growth factor (bFGF).
      OCP/Collagen (OCP/Col) or collagen disks were seeded with MSCs that had been pre
      incubated in osteogenic medium containing bFGF, which exhibited the highest
      differentiation induction, and then incubated for an additional day. The disks
      were implanted in critical-sized calvaria defects of 12-week-old male Wistar rats
      and the specimens were analysed radiographically, histologically,
      histomorphometrically, and by micro-computed tomography (CT) imaging at 4 and 8
      weeks after the implantation. The OCP/Col.MSCs group rapidly induced more bone
      regeneration, even within 4 weeks, compared to the OCP/Col group without MSCs.
      The bone mineral density of the OCP/Col.MSCs group was also greater than the
      OCP/Col group. The Col.MSCs group did not exhibit prominent osteogenicity. These
      results indicate that OCP crystals in a collagen matrix efficiently promote
      exogenously introduced osteogenic cells to initiate bone regeneration if the
      cells are pre-treated in a suitable differentiation condition.

PMID- 21892805
TI  - A stromal cell-derived factor-1 releasing matrix enhances the progenitor cell
      response and blood vessel growth in ischaemic skeletal muscle.
AB  - Although many regenerative cell therapies are being developed to replace or
      regenerate ischaemic muscle, the lack of vasculature and poor persistence of the
      therapeutic cells represent major limiting factors to successful tissue
      restoration. In response to ischaemia, stromal cell-derived factor-1 (SDF-1) is
      up-regulated by the affected tissue to stimulate stem cell-mediated regenerative
      responses. Therefore, we encapsulated SDF-1 into alginate microspheres and
      further incorporated these into an injectable collagen-based matrix in order to
      improve local delivery. Microsphere-matrix impregnation reduced the time for
      matrix thermogelation, and also increased the viscosity reached. This double
      incorporation prolonged the release of SDF-1, which maintained adhesive and
      migratory bioactivity, attributed to chemotaxis in response to SDF-1. In vivo,
      treatment of ischaemic hindlimb muscle with microsphere-matrix led to increased
      mobilisation of bone marrow-derived progenitor cells, and also improved
      recruitment of angiogenic cells expressing the SDF-1 receptor (CXCR4) from bone
      marrow and local tissues. Both matrix and SDF-1-releasing matrix were successful
      at restoring perfusion, but SDF-1 treatment appeared to play an earlier role, as
      evidenced by arterioles that are phenotypically older and by increased angiogenic
      cytokine production, stimulating the generation of a qualitative microenvironment
      for a rapid and therefore more efficient regeneration. These results support the
      release of implanted SDF-1 as a promising method for enhancing progenitor cell
      responses and restoring perfusion to ischaemic tissues via neovascularisation.

PMID- 21892817
TI  - Palladium-catalyzed amination of allyl alcohols.
AB  - An efficient catalytic amination of aryl-substituted allylic alcohols has been
      developed. The complex [(eta(3)-allyl)PdCl](2) modified by a bis phosphine
      ligand, L, has been used as catalyst in the reaction that afforded a wide range
      of allyl amines in good to excellent yield under mild conditions.

PMID- 21892818
TI  - Introduction of the conditional correlated Bernoulli model of similarity value
      distributions and its application to the prospective prediction of fingerprint
      search performance.
AB  - A statistical approach named the conditional correlated Bernoulli model is
      introduced for modeling of similarity scores and predicting the potential of
      fingerprint search calculations to identify active compounds. Fingerprint
      features are rationalized as dependent Bernoulli variables and conditional
      distributions of Tanimoto similarity values of database compounds given a
      reference molecule are assessed. The conditional correlated Bernoulli model is
      utilized in the context of virtual screening to estimate the position of a
      compound obtaining a certain similarity value in a database ranking. Through the
      generation of receiver operating characteristic curves from cumulative
      distribution functions of conditional similarity values for known active and
      random database compounds, one can predict how successful a fingerprint search
      might be. The comparison of curves for different fingerprints makes it possible
      to identify fingerprints that are most likely to identify new active molecules in
      a database search given a set of known reference molecules.

PMID- 21892819
TI  - Analysis of polychlorinated biphenyls in transformer oil by using liquid-liquid
      partitioning in a microfluidic device.
AB  - Polychlorinated biphenyls (PCBs) that are present in transformer oil are a common
      global problem because of their toxicity and environmental persistence. The
      development of a rapid, low-cost method for measurement of PCBs in oil has been a
      matter of priority because of the large number of PCB-contaminated transformers
      still in service. Although one of the rapid, low-cost methods involves an
      immunoassay, which uses multilayer column separation, hexane evaporation,
      dimethyl sulfoxide (DMSO) partitioning, antigen-antibody reaction, and a
      measurement system, there is a demand for more cost-effective and simpler
      procedures. In this paper, we report a DMSO partitioning method that utilizes a
      microfluidic device with microrecesses along the microchannel. In this method,
      PCBs are extracted and enriched into the DMSO confined in the microrecesses under
      the oil flow condition. The enrichment factor was estimated to be 2.69, which
      agreed well with the anticipated value. The half-maximal inhibitory concentration
      of PCBs in oil was found to be 0.38 mg/kg, which satisfies the much stricter
      criterion of 0.5 mg/kg in Japan. The developed method can realize the
      pretreatment of oil without the use of centrifugation for phase separation.
      Furthermore, the amount of expensive reagents required can be reduced
      considerably. Therefore, our method can serve as a powerful tool for achieving a
      simpler, low-cost procedure and an on-site analysis system.

PMID- 21892820
TI  - Highly adaptable and sensitive protease assay based on fluorescence resonance
      energy transfer.
AB  - Proteases are widely used in analytical sciences and play a central role in
      several widespread diseases. Thus, there is an immense need for highly adaptable
      and sensitive assays for the detection and monitoring of various proteolytic
      enzymes. We established a simple protease fluorescence resonance energy transfer
      (pro-FRET) assay for the determination of protease activities, which could in
      principle be adapted for the detection of all proteases. As proof of principle,
      we demonstrated the potential of our method using trypsin and enteropeptidase in
      complex biological mixtures. Briefly, the assay is based on the cleavage of a
      FRET peptide substrate, which results in a dramatic increase of the donor
      fluorescence. The assay was highly sensitive and fast for both proteases. The
      detection limits for trypsin and enteropeptidase in  Escherichia coli  lysate
      were 100 and 10 amol, respectively. The improved sensitivity for enteropeptidase
      was due to the application of an enzyme cascade, which leads to signal
      amplification. The pro-FRET assay is highly specific as even high concentrations
      of other proteases did not result in significant background signals. In
      conclusion, this sensitive and simple assay can be performed in complex
      biological mixtures and can be easily adapted to act as a versatile tool for the
      sensitive detection of proteases.

PMID- 21892821
TI  - Characterization of poly(sodium styrene sulfonate) thin films grafted from
      functionalized titanium surfaces.
AB  - Biointegration of titanium implants in the body is controlled by their surface
      properties. Improving surface properties by coating with a bioactive polymer is a
      promising approach to improve the biological performance of titanium implants. To
      optimize the grafting processes, it is important to fully understand the
      composition and structure of the modified surfaces. The main focus of this study
      is to provide a detailed, multitechnique characterization of a bioactive
      poly(sodium styrene sulfonate) (pNaSS) thin film grafted from titanium surfaces
      via a two-step procedure. Thin titanium films (~50 nm thick with an average
      surface roughness of 0.9 +/- 0.2 nm) prepared by evaporation onto silicon wafers
      were used as smooth model substrates. X-ray photoelectron spectroscopy (XPS) and
      time-of-flight secondary ion mass spectrometry (ToF-SIMS) showed that the
      titanium film was covered with a TiO(2) layer that was at least 10 nm thick and
      contained hydroxyl groups present at the outermost surface. These hydroxyl groups
      were first modified with a 3-methacryloxypropyltrimethoxysilane (MPS) cross
      linker. XPS and ToF-SIMS showed that a monolayer of the MPS molecules was
      successfully attached onto the titanium surfaces. The pNaSS film was grafted from
      the MPS-modified titanium through atom transfer radical polymerization. Again,
      XPS and ToF-SIMS were used to verify that the pNaSS molecules were successfully
      grafted onto the modified surfaces. Atomic force microscopy analysis showed that
      the film was smooth and uniformly covered the surface. Fourier transform infrared
      spectroscopy indicated that an ordered array of grafted NaSS molecules were
      present on the titanium surfaces. Sum frequency generation vibration spectroscopy
      and near edge X-ray absorption fine structure spectroscopy illustrated that the
      NaSS molecules were grafted onto the titanium surface with a substantial degree
      of orientational order in the styrene rings.

PMID- 21892822
TI  - Iridium(III) complex-coated nanosystem for ratiometric upconversion luminescence
      bioimaging of cyanide anions.
AB  - Chromophoric iridium(III) complex-coated NaYF(4): 20%Yb, 1.6%Er, 0.4%Tm
      nanocrystals are demonstrated as a ratiometric upconversion luminescence (UCL)
      probe for highly selective detection of cyanide anion and bioimaging of CN(-) in
      living cells through inhibition of the energy transfer from the UCL of the
      nanocrystals to the absorbance of the chromophoric complex. The UCL probe
      provides a very low detection limit of 0.18 MUM CN(-) in the aqueous solution.

PMID- 21892823
TI  - Poly(carboxybetaine methacrylamide)-modified nanoparticles: a model system for
      studying the effect of chain chemistry on film properties, adsorbed protein
      conformation, and clot formation kinetics.
AB  - Nonfouling polymer architectures are considered important to the successful
      implementation of many biomaterials. It is thought that how these polymers induce
      conformational changes in proteins upon adsorption may dictate the fate of the
      device being utilized. Herein, oxidized silicon nanoparticles (SiNP) were
      modified with various forms of poly(carboxybetaine methacrylamide) (PCBMA) for
      the express purpose of understanding how polymer chemistry affects film
      hydration, adsorbed protein conformation, and clot formation kinetics. To this
      end, carboxybetaine monomers differing in intercharge separating spacer groups
      were synthesized, and nitroxide-mediated free radical polymerization (NMP) was
      conducted using alkoxyamine initiators with hydrophobic (TEMPO) and hydrophilic
      (beta-phosphonate) terminal groups. The physical properties (surface composition,
      thickness, grafting density, etc.) of the resulting polymer-SiNP conjugates were
      quantified using several techniques, including Fourier transform infrared (FTIR)
      spectroscopy, dynamic light scattering (DLS), and thermogravimetric analysis
      (TGA). The effect of spacer group on the surface charge density was determined
      using zeta potential measurements. Three proteins, viz., lysozyme, bovine alpha
      lactalbumin, and human serum albumin, were used to evaluate the effect film
      properties (charge, hydration, end-group) have on adsorbed protein conformation,
      as determined by circular dichroism (CD), fluorescence spectroscopy, and
      fluorescence quenching techniques. Hemocompatibility of these surfaces was
      observed by measuring clot formation kinetics using the plasma recalcification
      time assay. It was found that chain chemistry, as opposed to end-group chemistry,
      was a major determiner for water structure, adsorbed protein conformation, and
      clotting kinetics. It is thought that the systematic evaluation of how both chain
      (internal) and end-group (external) polymer properties affect film hydration,
      protein conformation, and clot formation will provide valuable insight that can
      be applied to all engineered surfaces for biomedical applications.

PMID- 21892824
TI  - On the design of composite protein-quantum dot biomaterials via self-assembly.
AB  - Incorporation of nanoparticles during the hierarchical self-assembly of protein
      based materials can impart function to the resulting composite materials. Herein
      we demonstrate that the structure and nanoparticle distribution of composite
      fibers are sensitive to the method of nanoparticle addition and the
      physicochemical properties of both the nanoparticle and the protein. Our model
      system consists of a recombinant enhanced green fluorescent protein-Ultrabithorax
      (EGFP-Ubx) fusion protein and luminescent CdSe-ZnS core-shell quantum dots (QDs),
      allowing us to optically assess the distribution of both the protein and
      nanoparticle components within the composite material. Although QDs favorably
      interact with EGFP-Ubx monomers, the relatively rough surface morphology of
      composite fibers suggests EGFP-Ubx-QD conjugates impact self-assembly. Indeed,
      QDs templated onto EGFP-Ubx film post-self-assembly can be subsequently drawn
      into smooth composite fibers. Additionally, the QD surface charge impacts QD
      distribution within the composite material, indicating that surface charge plays
      an important role in self-assembly. QDs with either positively or negatively
      charged coatings significantly enhance fiber extensibility. Conversely, QDs
      coated with hydrophobic moieties and suspended in toluene produce composite
      fibers with a heterogeneous distribution of QDs and severely altered fiber
      morphology, indicating that toluene severely disrupts Ubx self-assembly.
      Understanding factors that impact the protein-nanoparticle interaction enables
      manipulation of the structure and mechanical properties of composite materials.
      Since proteins interact with nanoparticle surface coatings, these results should
      be applicable to other types of nanoparticles with similar chemical groups on the
      surface.

PMID- 21892826
TI  - Crucial effects of amino acid side chain length in transmembrane segment 5 on
      substrate affinity in yeast glucose transporter Hxt7.
AB  - We previously identified Asp(340) in transmembrane segment 7 (TM7) as a key
      determinant of substrate affinity in Hxt7, a high-affinity facilitative glucose
      transporter of Saccharomyces cerevisiae. To gain further insight into the
      structural basis of substrate recognition by Hxt7, we performed cysteine-scanning
      mutagenesis of 21 residues in TM5 of a Cys-less form of Hxt7. Four residues were
      sensitive to Cys replacement, among which Gln(209) was found to be essential for
      high-affinity glucose transport activity. The 17 remaining sites were examined
      further for the accessibility of cysteine to the hydrophilic sulfhydryl reagent p
      chloromercuribenzenesulfonate (pCMBS). Among the Cys mutants, T213C was the only
      one whose transport activity was completely inhibited by 0.5 mM pCMBS. Moreover,
      this mutant was protected from pCMBS inhibition by the substrate d-glucose and by
      2-deoxy-D-glucose but not by L-glucose, indicating that Thr(213) is situated at
      or close to a substrate recognition site. The functional role of Thr(213) was
      further examined with its replacement with each of the other 19 amino acids in
      wild-type Hxt7. Such replacement generated seven functional transporters with
      various affinities for glucose. Only three mutants, those with Val, Cys, and Ser
      at position 213, exhibited high-affinity glucose transport activity. All of these
      residues possess a side chain length similar to that of Thr, indicating that side
      chain length at this position is a key determinant of substrate affinity. A
      working homology model of Hxt7 indicated that Gln(209) and Thr(213) face the
      central cavity and that Thr(213) is located within van der Waals distance of
      Asp(340) (TM7).

PMID- 21892825
TI  - Degradation of ochratoxin a by Brevibacterium species.
AB  - The ability to degrade ochratoxin A was studied in different bacteria with a well
      known capacity to transform aromatic compounds. Strains belonging to Rhodococcus,
      Pseudomonas, and Brevibacterium genera were grown in liquid synthetic culture
      medium containing ochratoxin A. Brevibacterium spp. strains showed 100%
      degradation of ochratoxin A. Ochratoxin alpha was detected and identified by high
      performance liquid chromatography-mass spectrometry (HPLC-MS) as a degradation
      product in the cell-free supernatants. The degradation of ochratoxin A is of
      public concern for food and environmental safety, because it could contribute to
      the development of new biological ochratoxin A detoxification systems in
      foodstuffs. In this study, the degradation of ochratoxin A by bacteria belonging
      to the food chain was demonstrated for the first time.

PMID- 21892827
TI  - Colorimetric probes based on anthraimidazolediones for selective sensing of
      fluoride and cyanide ion via intramolecular charge transfer.
AB  - Probes based on anthra[1,2-d]imidazole-6,11-dione were designed and synthesized
      for selective ion sensing. Each probe acted as strong colorimetric sensors for
      fluoride and cyanide ions and exhibited intramolecular charge transfer (ICT)
      band, which showed significant red-shifts after addition of either the F(-) or
      CN(-) ion. One of the probes (2) showed selective colorimetric sensing for both
      cyanide and fluoride ions. In organic medium, 2 showed selective color change
      with fluoride and cyanide, whereas in aqueous organic medium it showed a
      ratiometric response selectively for cyanide ion.

PMID- 21892828
TI  - The mechanism of formation of N-formylkynurenine by heme dioxygenases.
AB  - Heme dioxygenases catalyze the oxidation of L-tryptophan to N-formylkynurenine
      (NFK), the first and rate-limiting step in tryptophan catabolism. Although recent
      progress has been made on early stages in the mechanism, there is currently no
      experimental data on the mechanism of product (NFK) formation. In this work, we
      have used mass spectrometry to examine product formation in a number of
      dioxygenases. In addition to NFK formation (m/z = 237), the data identify a
      species (m/z = 221) that is consistent with insertion of a single atom of oxygen
      into the substrate during O(2)-driven turnover. The fragmentation pattern for
      this m/z = 221 species is consistent with a cyclic amino acetal structure;
      independent chemical synthesis of the 3a-hydroxypyrroloindole-2-carboxylic acid
      compound is in agreement with this assignment. Labeling experiments with (18)O(2)
      confirm the origin of the oxygen atom as arising from O(2)-dependent turnover.
      These data suggest that the dioxygenases use a ring-opening mechanism during NFK
      formation, rather than Criegee or dioxetane mechanisms as previously proposed.

PMID- 21892829
TI  - Phosphoramidate ProTides of the anticancer agent FUDR successfully deliver the
      preformed bioactive monophosphate in cells and confer advantage over the parent
      nucleoside.
AB  - The fluorinated pyrimidine family of nucleosides continues to represent major
      current chemotherapeutic agents for treating solid tumors. We herein report their
      phosphate prodrugs, ProTides, as promising new derivatives, which partially
      bypass the dependence of the current drugs on active transport and nucleoside
      kinase-mediated activation. They are also resistant to metabolic deactivation by
      phosphorolytic enzymes. We report 39 ProTides of the fluorinated pyrimidine FUDR
      with variation in the aryl, ester, and amino acid regions. Notably, only certain
      ProTide motifs are successful in delivering the nucleoside monophosphate into
      intact cells. We also find that the ProTides retain activity in mycoplasma
      infected cells, unlike FUDR. Data suggest these compounds to be worthy of further
      progression.

PMID- 21892830
TI  - Temperature-programmed precise control over the sizes of carbon nanospheres based
      on benzoxazine chemistry.
AB  - On the basis of benzoxazine chemistry, we have established a new way to
      synthesize highly uniform carbon nanospheres with precisely tailored sizes and
      high monodispersity. Using monomers including resorcinol, formaldehyde, and 1,6
      diaminohexane, and in the presence of Pluronic F127 surfactant, polymer
      nanospheres are first synthesized under precisely programmed reaction
      temperatures. Subsequently, they are pseudomorphically and uniformly converted to
      carbon nanospheres in high yield, due to the excellent thermal stability of such
      polybenzoxazine-based polymers. The correlation between the initial reaction
      temperature (IRT) and the nanosphere size fits well with the quadratic function
      model, which can in turn predict the nanosphere size at a set IRT. The nanosphere
      sizes can easily go down to 200 nm while retaining excellent monodispersity,
      i.e., polydispersity <5%. The particle size uniformity is evidenced by the
      formation of large areas of periodic assembly structure. NMR, FT-IR, and
      elemental analyses prove the formation of a polybenzoxazine framework. As a
      demonstration of their versatility, nanocatalysts composed of highly dispersed Pd
      nanoparticles in the carbon nanospheres are fabricated, which show high
      conversion and selectivity, great reusability, and regeneration ability, as
      evidenced in a selective oxidation of benzyl alcohol to benzaldehyde under
      moderate conditions.

PMID- 21892831
TI  - Characterization and antioxidant activity of the complex of tea polyphenols and
      oat beta-glucan.
AB  - Few data are available about the effects of complexation of polyphenols with
      polysaccharide on their bioavailability. The complex of tea polyphenols (TP) with
      oat beta-glucan was characterized by ultraviolet-visible spectrometry, Fourier
      transform infrared spectrometry, differential scanning calorimetry, atomic force
      microscopy, and solid-state (13)C NMR spectroscopy. The results indicated that
      the bonds which governed the interaction between TP and oat beta-glucan were
      strong hydrogen bonds. The in vitro antioxidant activity of TP, beta-glucan,
      their complex, and physical mixture was assessed using four systems, namely,
      DPPH(*), OH(*), and O(2)(*-) scavenging activities and reducing power. The
      complexation and blending of TP and beta-glucan exhibited different impacts on
      the index of in vitro and in vivo antioxidant capacities. In the concentration
      range of 0.5-2.5 mg mL(-1), the complex had highest O(2)(*-) scavenging activity,
      whereas the highest OH(*) scavenging activity was found with the physical
      mixture. For antioxidant testing in vivo, there was no significant difference
      between the complex and the physical mixture in terms of glutathione peroxidase
      activity and levels of malondialdehyde and total antioxidant capacity in serums.
      However, the complex exhibited much higher activities of superoxide dismutase and
      glutathione peroxidase in livers than the physical mixture. The present study
      provided a deeper understanding of the influence of molecular interaction between
      TP and oat beta-glucan on their antioxidant activities.

PMID- 21892832
TI  - Designed glucose-responsive microgels with selective shrinking behavior.
AB  - We report on the synthesis of various glucose-responsive microgels based on N
      alkylacrylamide derivatives and phenylboronic acid (PBA) as a glucose sensing
      moiety. Depending on their chemical composition, the microgels exhibit opposite
      behaviors in response to glucose concentration increase: they can either swell or
      shrink, using two different mechanisms for glucose recognition. Both behaviors
      may be suitable for glucose sensing and insulin delivery. When glucose binds a
      single boronate receptor, the microgel swells as glucose concentration increases.
      This mechanism can be used to deliver a drug by diffusion through the network. In
      other cases, glucose binds specifically to two boronates, which creates
      additional cross-links within the network and provokes shrinkage. Such systems
      are promising for the development of sensors with improved selectivity and also
      as potential "intelligent" valves in microfabricated delivery systems. By a
      rational choice of the constituting units of the network structure, we show how
      to favor one or the other type of response to glucose variation. Therefore,
      glucose-swelling microgels operating under physiological conditions have been
      obtained by copolymerization with an appropriate choice of alkylacrylamide
      monomer and boronate derivative. At a pH above the pK(a) of the boronic acid
      derivative, the same structures shrink in response to glucose concentration. The
      nature of the cross-linker is a key parameter to enable this dual behavior. In
      other microgels, an amine group is introduced in the vicinity of the boronic
      acid, which lowers its pK(a) and favors microgel contraction at physiological pH.
      This work has allowed us to give some general rules to control the
      swelling/shrinking behavior of glucose-responsive microgels.

PMID- 21892833
TI  - Structural basis for inhibiting beta-amyloid oligomerization by a non-coded beta
      breaker-substituted endomorphin analogue.
AB  - The distribution of endomorphins (EM) 1 and 2 in the human brain inversely
      correlates with cerebral neurodegeneration in Alzheimer's disease (AD), implying
      a protective role. These endogenous opioid peptides incorporate aromatic residues
      and a beta-breaker motif, as seen in several optimized inhibitors of Abeta
      aggregation. The activity of native endomorphins was studied, as well as the
      rationally designed analogue Aib-1, which includes a remarkably efficient beta
      breaker, alpha-aminoisobutyric acid (Aib). In vitro and GFP fusion protein assays
      showed that Aib-1 interacted with Abeta and markedly inhibited the formation of
      toxic oligomer and fibril growth. Moreover, Aib-1 prevented the toxicity of Abeta
      toward neuronal PC12 cells and markedly rectified reduced longevity of an AD fly
      model. Atomistic simulations and NMR-derived solution structures revealed that
      Aib-1 significantly reduced the propensity of Abeta to aggregate due to multimode
      interactions including aromatic, hydrophobic, and polar contacts. We suggest that
      hindering the self-assembly process by interfering with the aromatic core of
      amyloidogenic peptides may pave the way toward developing therapeutic agents to
      treat amyloid-associated diseases.

PMID- 21892834
TI  - Sc(OTf)3-catalyzed synthesis of indoles and SnCl4-mediated regioselective
      hydrochlorination of 5-(arylamino)pent-3-yn-2-ones.
AB  - Highly substituted indole derivatives bearing alkyl and aryl moieties can be
      prepared by Sc(OTf)(3)-catalyzed Friedel-Crafts alkenylation of 5-(arylamino)pent
      3-yn-2-ones. In addition, a method for regioselective hydrochlorination of 5
      (arylamino)pent-3-yn-2-ones mediated by SnCl(4) in moderate to good yields (up to
      84%) has been developed. The resulting exclusive Z-selectivity of the C-Cl bond
      can be further exploited using cross C-N coupling reactions.

PMID- 21892835
TI  - Ambient pressure proton transfer mass spectrometry: detection of amines and
      ammonia.
AB  - An instrument to detect gaseous amines and ammonia is described, and
      representative data from an urban site and a laboratory setting are presented.
      The instrument, an Ambient pressure Proton transfer Mass Spectrometer (AmPMS),
      consists of a chemical ionization and drift region at atmospheric pressure
      coupled to a standard quadrupole mass spectrometer. Calibrations show that AmPMS
      sensitivity is good for amines, and AmPMS backgrounds were suitably determined by
      diverting sampled air through a catalytic converter. In urban air at a site in
      Atlanta, amines were detected at subpptv levels for methyl and dimethyl amine
      which were generally at a low abundance of <1 and ~3 pptv, respectively.
      Trimethyl amine (or isomers) was on average about 4 pptv in the morning and
      increased to 15 pptv in the afternoon, while triethyl amine (or isomers or
      amides) increased to 25 pptv on average in the late afternoon. The background
      levels for the 4 and 5 carbon amines and ammonia were high, and data are very
      limited for these species. Improvements in detecting amines and ammonia from a
      smog chamber were evident due to improvements in AmPMS background determination;
      notably dimethyl amine and its OH oxidation products were followed along with
      impurity ammonia and other species. Future work will focus on accurate
      calibration standards and on improving the sample gas inlet.

PMID- 21892837
TI  - Engineered streptavidin monomer and dimer with improved stability and function.
AB  - Although streptavidin's high affinity for biotin has made it a widely used and
      studied binding protein and labeling tool, its tetrameric structure may interfere
      with some assays. A streptavidin mutant with a simpler quaternary structure would
      demonstrate a molecular-level understanding of its structural organization and
      lead to the development of a novel molecular reagent. However, modulating the
      tetrameric structure without disrupting biotin binding has been extremely
      difficult. In this study, we describe the design of a stable monomer that binds
      biotin both in vitro and in vivo. To this end, we constructed and characterized
      monomers containing rationally designed mutations. The mutations improved the
      stability of the monomer (increase in T(m) from 31 to 47  degrees C) as well as
      its affinity (increase in K(d) from 123 to 38 nM). We also used the stability
      improved monomer to construct a dimer consisting of two streptavidin subunits
      that interact across the dimer-dimer interface, which we call the A/D dimer. The
      biotin binding pocket is conserved between the tetramer and the A/D dimer, and
      therefore, the dimer is expected to have a significantly higher affinity than the
      monomer. The affinity of the dimer (K(d) = 17 nM) is higher than that of the
      monomer but is still many orders of magnitude lower than that of the wild-type
      tetramer, which suggests there are other factors important for high-affinity
      biotin binding. We show that the engineered streptavidin monomer and dimer can
      selectively bind biotinylated targets in vivo by labeling the cells displaying
      biotinylated receptors. Therefore, the designed mutants may be useful in novel
      applications as well as in future studies in elucidating the role of
      oligomerization in streptavidin function.

PMID- 21892838
TI  - Unraveling the human bone microenvironment beyond the classical extracellular
      matrix proteins: a human bone protein library.
AB  - A characteristic feature of bone, differentiating it from other connective
      tissues, is the mineralized extracellular matrix (ECM). Mineral accounts for the
      majority of the bone tissue volume, being the remainder organic material mostly
      derived from collagen. This, and the fact that only a limited number of
      noncollagenous ECM proteins are described, provides a limited view of the bone
      tissue composition and bone metabolism, the more so considering the increasing
      understanding of ECM significance for cellular form and function. For this
      reason, we set out to analyze and extensively characterize the human bone
      proteome using large-scale mass spectrometry-based methods. Bone samples of four
      individuals were analyzed identifying 3038 unique proteins. A total of 1213 of
      these were present in at least 3 out of 4 bone samples. For quantification
      purposes, we were limited to noncollagenous proteins (NCPs) and we could quantify
      1051 NCPs. Most classical bone matrix proteins mentioned in literature were
      detected but were not among the highly abundant ones. Gene ontology analyses
      identified high-abundance groups of proteins with a functional link to
      mineralization and mineral metabolism such as transporters, pyrophosphatase
      activity, and Ca(2+)-dependent phospholipid binding proteins. ECM proteins were
      as well overrepresented together with nucleosome and antioxidant activity
      proteins, which have not been extensively characterized as being important for
      bone. In conclusion, our data clearly demonstrates that human bone tissue is a
      reservoir of a wide variety of proteins. In addition to the classical osteoblast
      derived ECM, we have identified many proteins from different sources and of
      unknown function in bone. Thus, this study represents an informative library of
      bone proteins forming a source for novel bone formation modulators as well as
      biomarkers for bone diseases such as osteoporosis.

PMID- 21892836
TI  - Structural characterization and high-throughput screening of inhibitors of PvdQ,
      an NTN hydrolase involved in pyoverdine synthesis.
AB  - The human pathogen Pseudomonas aeruginosa produces a variety of virulence factors
      including pyoverdine, a nonribosomally produced peptide siderophore. The
      maturation pathway of the pyoverdine peptide is complex and provides a unique
      target for inhibition. Within the pyoverdine biosynthetic cluster is a
      periplasmic hydrolase, PvdQ, that is required for pyoverdine production. However,
      the precise role of PvdQ in the maturation pathway has not been biochemically
      characterized. We demonstrate herein that the initial module of the nonribosomal
      peptide synthetase PvdL adds a myristate moiety to the pyoverdine precursor. We
      extracted this acylated precursor, called PVDIq, from a pvdQ mutant strain and
      show that the PvdQ enzyme removes the fatty acid catalyzing one of the final
      steps in pyoverdine maturation. Incubation of PVDIq with crystals of PvdQ allowed
      us to capture the acylated enzyme and confirm through structural studies the
      chemical composition of the incorporated acyl chain. Finally, because inhibition
      of siderophore synthesis has been identified as a potential antibiotic strategy,
      we developed a high-throughput screening assay and tested a small chemical
      library for compounds that inhibit PvdQ activity. Two compounds that block PvdQ
      have been identified, and their binding within the fatty acid binding pocket was
      structurally characterized.

PMID- 21892839
TI  - Atmospheric reaction of the HOSO radical with NO2: a theoretical study.
AB  - The gas-phase reaction between HOSO and NO(2) was examined using density
      functional theory. Geometry optimizations and frequency computations were
      performed at the B3LYP/6-311++G(2df,2pd) level of theory for all minimum species
      and transition states. The ground-state potential energy surface, including
      activation energies and enthalpies, were calculated using the ab initio CBS-QB3
      composite method. The results suggest that the addition of HOSO and NO(2) leads
      to two possible intermediates, HOS(O)NO(2) and HOS(O)ONO, without any energy
      barrier. The HOS(O)NO(2) easily decomposes into HONO + SO(2) through the low
      energy product complex HONO...SO(2), whereas the HOS(O)ONO dissociates to HOSO(2)
      + NO products. This latter dissociation is preferred from the isomerization of
      the HOS(O)ONO to HOS(NO)O(2). Also, HOS(O)NO(2) isomerization to HOS(O)ONO is
      hindered due to the presence of a large energy barrier. From the thermodynamic
      aspect, the main products in the title reaction are HONO + SO(2), whereas HOSO(2)
      + NO are expected as a minor products.

PMID- 21892840
TI  - Cost effectiveness of self-monitoring of blood glucose (SMBG) for patients with
      type 2 diabetes and not on insulin: impact of modelling assumptions on recent
      Canadian findings.
AB  - BACKGROUND: Canadian patients, healthcare providers and payers share interest in
      assessing the value of self-monitoring of blood glucose (SMBG) for individuals
      with type 2 diabetes but not on insulin. Using the UKPDS (UK Prospective Diabetes
      Study) model, the Canadian Optimal Prescribing and Utilization Service (COMPUS)
      conducted an SMBG cost-effectiveness analysis. Based on the results, COMPUS does
      not recommend routine strip use for most adults with type 2 diabetes who are not
      on insulin. Cost-effectiveness studies require many assumptions regarding cohort,
      clinical effect, complication costs, etc. The COMPUS evaluation included several
      conservative assumptions that negatively impacted SMBG cost effectiveness.
      OBJECTIVES: Current objectives were to (i) review key, impactful COMPUS
      assumptions; (ii) illustrate how alternative inputs can lead to more favourable
      results for SMBG cost effectiveness; and (iii) provide recommendations for
      assessing its long-term value. METHODS: A summary of COMPUS methods and results
      was followed by a review of assumptions (for trial-based glycosylated haemoglobin
      [HbA(1c)] effect, patient characteristics, costs, simulation pathway) and their
      potential impact. The UKPDS model was used for a 40-year cost-effectiveness
      analysis of SMBG (1.29 strips per day) versus no SMBG in the Canadian payer
      setting. COMPUS assumptions for patient characteristics (e.g. HbA(1c) 8.4%), SMBG
      HbA(1c) advantage (-0.25%) and costs were retained. As with the COMPUS analysis,
      UKPDS HbA(1c) decay curves were incorporated into SMBG and no-SMBG pathways. An
      important difference was that SMBG HbA(1c) benefits in the current study could
      extend beyond the initial simulation period. Sensitivity analyses examined SMBG
      HbA(1c) advantage, adherence, complication history and cost inputs. Outcomes
      (discounted at 5%) included QALYs, complication rates, total costs (year 2008
      values) and incremental cost-effectiveness ratios (ICERs). RESULTS: The base-case
      ICER was $Can63 664 per QALY gained; approximately 56% of the COMPUS base-case
      ICER. SMBG was associated with modest risk reductions (0.10-0.70%) for six of
      seven complications. Assuming an SMBG advantage of -0.30% decreased the current
      base-case ICER by over $Can10 000 per QALY gained. With adherence of 66% and 87%,
      ICERs were (respectively) $Can39 231 and $Can54 349 per QALY gained.
      Incorporating a more representative complication history and 15% complication
      cost increase resulted in an ICER of $Can49 743 per QALY gained. CONCLUSIONS:
      These results underscore the importance of modelling assumptions regarding the
      duration of HbA(1c) effect. The current study shares several COMPUS limitations
      relating to the UKPDS model being designed for newly diagnosed patients, and to
      randomized controlled trial monitoring rates. Neither study explicitly examined
      the impact of varying the duration of initial HbA(1c) effects, or of medication
      or other treatment changes. Because the COMPUS research will potentially
      influence clinical practice and reimbursement policy in Canada, understanding the
      impact of assumptions on cost-effectiveness results seems especially important.
      Demonstrating that COMPUS ICERs were greatly reduced through variations in a
      small number of inputs may encourage additional clinical research designed to
      measure SMBG effects within the context of optimal disease management. It may
      also encourage additional economic evaluations that incorporate lessons learned
      and best practices for assessing the overall value of SMBG for type 2 diabetes in
      insulin-naive patients.

PMID- 21892842
TI  - Employee adjustment to stress: The role of coping resources, situational factors,
      and coping responses.
AB  - Abstract The present study was designed to examine further the stress-adjustment
      relationship in employees. Specifically, the relations among employees' coping
      resources (self-esteem, generalized control beliefs, neuroticism, and social
      support), their appraisals of a recent stressful event experienced at work
      (appraised stress, self-efficacy, and situational control beliefs), the coping
      strategies (problem- and emotion-focused coping) used to deal with the event, and
      levels of employee adjustment (psychological well-being and job satisfaction)
      were examined. Data were collected from 153 male and female employees in a public
      sector department, employed in a range of middle-management administrative
      activities. The data provided support for a modified version of a model that
      proposed that both situational appraisals and coping strategies are mediating
      processes in the stress-adjustment relationship. There was evidence that
      employees' coping responses to the recent stressful event experienced at work
      were related to concurrent levels of adjustment. As predicted, the use of problem
      focused coping, in general, had positive relationships with the measures of
      adjustment, whereas the effects of emotion-focused coping were generally negative
      (there was, however, some evidence that the effects of coping were dependent on
      event controllability). There was also evidence that coping resources had both
      direct and indirect effects (via coping and via situational appraisals) on
      employee adjustment. The latter effects were most marked for generalized control
      beliefs and self-esteem. Situational appraisals (in particular, efficacy
      expectancies) also had indirect effects on employee adjustment, through their
      effects on coping responses.

PMID- 21892843
TI  - Trait anxiety, work demand, social support and psychological distress in
      correctional officers.
AB  - Abstract This study examined the role of social support in the relationship
      between work demand and psychological distress (GHQ 12) in correctional officers
      (N=419), a high stress occupational group. Work demands were positively
      associated with strain. There was no evidence that social support buffered the
      negative impact of work demands. Rather, consistent with most previous research
      findings, support showed direct benefits and these were discussed in the context
      of worker participation and control. The hypothesis that officers high in
      negative affectivity, as measured by trait anxiety would show greater reactivity
      to work demands was not supported. However, trait anxiety appeared to inflate the
      relationship between work stressors (work demand and work support) and
      psychological distress supporting recent suggestions that the role of trait
      anxiety in occupational stress should not be disregarded. Trait anxiety combined
      additively with work demand to predict individual differences in psychological
      distress, however social support moderated the impact of trait anxiety on strain.

PMID- 21892841
TI  - JAKs go nuclear: emerging role of nuclear JAK1 and JAK2 in gene expression and
      cell growth.
AB  - The four Janus kinases (JAKs) comprise a family of intracellular, nonreceptor
      tyrosine kinases that first gained attention as signaling mediators of the type I
      and type II cytokine receptors. Subsequently, the JAKs were found to be involved
      in signaling downstream of the insulin receptor, a number of receptor tyrosine
      kinases, and certain G-protein coupled receptors. Although a number of
      cytoplasmic targets for the JAKs have been identified, their predominant action
      was found to be the phosphorylation and activation of the signal transducers and
      activators of transcription (STAT) factors. Through the STATs, the JAKs activate
      gene expression linked to cellular stress, proliferation, and differentiation.
      The JAKs are especially important in hematopoiesis, inflammation, and immunity,
      and aberrant JAK activity has been implicated in a number of disorders including
      rheumatoid arthritis, psoriasis, polycythemia vera, and myeloproliferative
      diseases. Although once thought to reside strictly in the cytoplasm, recent
      evidence shows that JAK1 and JAK2 are present in the nucleus of certain cells
      often under conditions associated with high rates of cell growth. Nuclear JAKs
      have now been shown to affect gene expression by activating other transcription
      factors besides the STATs and exerting epigenetic actions, for example, by
      phosphorylating histone H3. The latter action derepresses global gene expression
      and has been implicated in leukemogenesis. Nuclear JAKs may have a role as well
      in stem cell biology. Here we describe recent developments in understanding the
      noncanonical nuclear actions of JAK1 and JAK2.

PMID- 21892844
TI  - Looking at threat-relevant stimuli: The role of anxiety and coping style.
AB  - Abstract Results of numerous studies demonstrate that anxious subjects
      selectively attend to threat-related rather than to neutral stimuli. It has been
      argued that, as a result of this, anxious individuals more easily perceive and
      misattribute threatening stimuli in their environment, thereby creating a vicious
      circle of attention and anxiety. The evidence for this anxiety-linked attentional
      bias, however, is largely based on studies using subliminal or dichotic
      presentation of verbal stimuli. The present study sought to replicate these
      results by examining the relationship between anxiety and visual attention during
      prolonged exposure to threat-relevant (pictures of situations in a dental
      practice) and neutral (pictures of situations at a hairdresser salon) material
      with 45 women. No significant relationship emerged between dental trait anxiety
      and duration subjects directed gaze to the threat-relevant pictures. Neither self
      reported state anxiety nor habitual coping style appeared to be significantly
      related to duration of visual attention for the threat-relevant pictures. Hence,
      no evidence was found supporting the hypothesis that high anxiety leads to a bias
      in attention towards emotionally threatening information. It is suggested that
      hypervigilance occurs in the early stages of the appraisal process.

PMID- 21892845
TI  - Imposed and chosen monitoring and blunting strategies in the dental setting:
      Effects, self-efficacy, and coping preference.
AB  - Abstract In the present study, 94 dental patients received either monitoring
      (i.e., paying attention) or blunting (i.e., distraction) coping instructions
      during treatment. Half of the patients were given the possibility of choice,
      whereas the other half were offered one of both strategies without choice. A
      majority of the patients (n=61) indicated that the intervention had resulted in a
      decrease of their anxiety. Some indications were found for the monitoring
      strategy to be more effective than the blunting strategy. More specifically,
      monitoring strategy subjects reported that they had experienced less distress
      during treatment than blunting strategy subjects. In agreement with this finding,
      self-efficacy ratings of monitoring strategy subjects were higher than those of
      blunting strategy subjects. Possibility of choice and coping preference had no
      substantial influence on effectiveness of the interventions.

PMID- 21892846
TI  - A dutch adaptation of the child-rearing styles inventory and a validation of
      krohne's two-process model.
AB  - Abstract A Questionnaire for the Parent-Child Interaction (VOKI) has been
      developed by adapting Krohne's German ESI for the Flemish high school population.
      The psychometric characteristics of the adaptation are satisfying. The ESI factor
      structure has been replicated and the VOKI scales are perfectly comparable to the
      original German scales. Further research on the VOKI and two questionnaires
      assessing achievement related concepts such as test anxiety, procrastination and
      achievement motivation yielded correlational patterns partly predicted from
      Krohne's Two-Process Model. The relations between parental child-rearing styles
      and competence and consequence expectancies are in line with this model, whereas
      test anxiety and procrastination seem more complexly determined.

PMID- 21892847
TI  - Effects of test anxiety, ego stress, and attentional skills training on
      arithmetic reasoning: An experimental evaluation of a brief counseling strategy.
AB  - Abstract Two hundred forty high school students (120 male and 120 female) in
      India performed a moderately difficult multiple choice Arithmetic Reasoning task
      after undergoing short-term (40 minutes) cognitive treatment in the form of
      Attentional Skills Training. A 2 * 2 * 2 (Test Anxiety x Attentional Skills
      Training x Stress) design with separate analysis for boys and girls indicated
      these results: with intervention the high anxiety subjects under ego stress
      conditions, compared to their high-anxious control, low-anxious ego stress, or
      low-anxious control counterparts, reported the maximum significant improvement in
      performance on the Arithmetic Reasoning test. The low-anxiety subjects performed
      consistently well with or without treatment or stress conditions. The findings
      shed new light on the attentional theory of test anxiety, and it was reasoned
      that long-term effects of cognitive treatment be studied by using varied
      performance tasks (difficulty level controlled) on different gender and age
      groups across cultures.

PMID- 21892848
TI  - Cognitive effects of life stress and learned helplessness.
AB  - Abstract Stressful life events and learned helplessness attributional styles have
      been shown to impact a variety of personal outcomes. This study examined how
      these factors influence two classes of cognitive behaviors: the occurrence of
      intrusive thoughts and performance in memory and verbal-spatial reasoning tasks.
      Negative life change and attributions for negative events predicted different
      types of cognitive responses. Individuals reporting higher levels of life stress
      were more likely to experience distracting thoughts that were unrelated to the
      current task, whereas individuals with learned helplessness attributional styles
      tended to have more worrisome thoughts about their task performance. In general,
      individuals reporting high levels of negative life stress tended to perform more
      poorly in tasks, whereas individuals with learned helplessness attributional
      styles tended to perform better than those who did not share this explanatory
      style. These results suggest that life stress and attributional style have
      important influecnes on cognitive processes, and that a learned helplessness
      attributional style can have beneficial effects on behavior in some situations.

PMID- 21892849
TI  - Anxiety and heart rate under psychological stress: The effects of exercise
      training.
AB  - Abstract The effects of a 12-week exercise-training program on cognitive,
      somatic, and behavioral anxiety and on heart rate responses to evaluative stress
      were scrutinized in 89 subjects randomly assigned to an experimental (exercise)
      or a control group. The training program consisted of exercises that were aimed
      to the improvement of the general physical fitness (i.e., strength, flexibility,
      and endurance). Following the 12-week training period, exercising subjects showed
      improved motor skill capacity as well as higher VO(2) max. In an anxiety inciting
      test situation, that consisted of the video-taped delivery of a 5-min speech, a
      mental arithmetic and a fine motor task, exercising subjects showed more
      favourable responses than control subjects in three ways: (a) they exhibited
      lower behavioral anxiety during the anticipation phase of the three stressors,
      (b) they reported lower cognitive and somatic anxiety during the anxiety
      provoking situation, and (c) their heart rate recovered faster, in contrast to
      both their baseline heart rate and the control subjects' heart rate, from the
      stress episode. These results demonstrate that a fitness-oriented exercise
      program has anxiolytic properties. They also provide a primary evidence that
      overt behavioral anxiety, as opposed to the usually measured self-reported
      anxiety, may be affected by exercise.

PMID- 21892850
TI  - Performance realism in test-anxious students.
AB  - Abstract Twenty-four high test-anxious and 24 low test-anxious students completed
      two cognitive tasks under either high or low performance demand manipulations.
      Before each task subjects rated anxiety levels and performance expectations, with
      performance evaluations being conducted following completion of each task.
      Results revealed lower actual, anticipated and self-evaluated performance scores
      for high test-anxious students compared to their low test-anxious counterparts.
      Expected and self-evaluated performance ratings were then compared with actual
      performance. No difference was found between high and low test-anxious subjects
      in terms of the discrepancy between expected and actual performance. Both groups
      of students tended to be overoptimistic in their performance predictions.
      However, following the first cognitive task the test-anxious group demonstrated
      accurate self-evaluation, whereas the low test-anxious group were overoptimistic
      in their self-evaluation. This effect was not found for the second task, on which
      both groups were accurate in their performance-evaluation. The results are
      discussed in terms of cognitive theories of anxiety, self-focussed attention and
      realism amongst test-anxious students.

PMID- 21892851
TI  - Emotional correlates of body weight: The moderating effects of gender and family
      income.
AB  - Abstract This study explored emotional correlates of relative body weight in a
      sample of 187 male and 269 female college students. The contribution of relative
      body weight, gender, family income and their interactions to variables related to
      anxiety and anger were evaluated by multiple regression procedures. Relative body
      weight was positively related to trait anxiety, especially among those with lower
      family incomes. Increased body weight was also related to trait anger and an
      anger-out expression style, but only among men. These results suggest that gender
      and family income moderate the contribution of relative body weight to anxiety
      and anger, both central aspects of a 'disease-prone personality'

PMID- 21892853
TI  - The role of ezetimibe in LDL cholesterol goal attainment in very high risk
      patients: the rosuvastatin monotherapy looks to be insufficient.

PMID- 21892854
TI  - Predictors of government subsidized pharmaceutical use in patients with diabetes
      or cardiovascular disease in a primary care setting: evidence from a prospective
      randomized trial.
AB  - OBJECTIVES: This study uses data from a prospective randomized controlled trial
      to estimate predictors of pharmaceutical expenditure in diabetes (DM) or
      cardiovascular disease (CVD) patients. Identifying drivers of pharmaceutical use
      and the extent to which they are modifiable may inform cost-effective policy
      making. METHODS: The trial followed 260 patients aged >18 years (mean 68) from
      three general practices for 12 months. Patients had type 2 diabetes (90 patients)
      or cardiovascular disease (170 patients). Costs for pharmaceuticals prescribed on
      the Pharmaceutical Benefits Scheme (PBS) were obtained retrospectively at 12
      months. Sociodemographic data and health-related quality-of-life (QoL) were
      recorded from questionnaires. Clinical measures (including body mass index (BMI),
      blood pressure, high and low density lipoprotein (LDL), and HbA1c) were also
      collected. RESULTS: Mean pharmaceutical costs for DM patients (AU$4119) was
      greater than CVD patients (AU$2424). The largest contributor to costs in both
      groups was pharmaceuticals used for management of conditions other than CVD or
      DM. QoL (EQ5D) and BMI were significant predictors of costs in both groups. A
      history of cardiac events, HbA1c, age, and unemployment were significant
      predictors of costs in the DM group. A diagnosis of heart failure, frequency of
      hospital admissions, and LDL levels were significant predictors of costs in the
      CVD group. Roughly one third of total variation of costs can be explained by the
      regressors in both models. LIMITATIONS: Generalizability will be limited as data
      was derived from a trial and the study was not powered for this post-hoc
      analysis. Missing data imputation and self-reporting bias may also impact on
      results. CONCLUSIONS: Factors such as QoL BMI, HbA1c levels, and a history of
      cardiac events are significant predictors of costs. The results suggest there may
      be a place for interventions that improve quality-of-life and concurrently reduce
      pharmaceutical costs in patients with CVD or DM.

PMID- 21892855
TI  - Hypoglycemia in patients with type 2 diabetes using concomitant exenatide BID and
      long-acting insulin therapy.
AB  - OBJECTIVE: The objective of this study was to examine the frequency of
      hypoglycemia among patients with type 2 diabetes who had concomitantly used
      exenatide BID (exenatide) and long-acting insulin and continued this combination
      vs those who continued long-acting insulin alone. METHODS: Retrospective
      analyses, using a large managed care database, were used to estimate the
      frequency of hypoglycemia (episodes/patient/6 months) for patients who
      concomitantly used exenatide and long-acting insulin during a 6-month follow-up
      period. RESULTS: From among 2082 patients on concomitant exenatide and long
      acting insulin, those who continued this combination (n=472) had a lower
      frequency of hypoglycemia compared to those who remained on long-acting insulin
      alone (n=312) (0.03 +/- 1.9 vs 0.10 +/- 1.01 [episodes/patient/6 months];
      p<0.0001). LIMITATIONS: Only hypoglycemia that required medical intervention
      (coded for hypoglycemia) was captured. The study could not evaluate any
      association between insulin dose titration and hypoglycemia or examine other
      outcomes such as HbA1c, weight, and body mass index, due to lack of data
      availability. CONCLUSIONS: Patients who concomitantly used exenatide BID and long
      acting insulin experienced a lower rate of hypoglycemia.

PMID- 21892856
TI  - Cost-effectiveness of novel relapsed-refractory multiple myeloma therapies in
      Norway: lenalidomide plus dexamethasone vs bortezomib.
AB  - OBJECTIVE: To estimate the cost-effectiveness (cost per additional life-year [LY]
      and quality-adjusted life-year [QALY] gained) of lenalidomide plus dexamethasone
      (LEN/DEX) compared with bortezomib for the treatment of relapsed-refractory
      multiple myeloma (rrMM) in Norway. METHODS: A discrete-event simulation model was
      developed to predict patients? disease course using patient data, best response,
      and efficacy levels obtained from LEN/DEX MM-009/-010 trials and the bortezomib
      (APEX) published clinical trial. Predictive equations for time-to-progression
      (TTP) and post-progression survival (PPS) were developed by identifying the best
      fitting parametric survival distributions and selecting the most significant
      predictors. Disease and adverse event management was obtained via survey from
      Norwegian experts. Costs, derived from official Norwegian pricing data bases,
      included drug, administration, monitoring, and adverse event management costs.
      RESULTS: Complete or partial responders were 65% for LEN/DEX compared to 43% for
      bortezomib. Derived median TTP was 11.45 months for LEN/DEX compared to 5.15
      months for bortezomib. LYs and QALYs were higher for LEN/DEX (4.06 and 2.95,
      respectively) than for bortezomib (3.11 and 2.19, respectively). The incremental
      costs per QALY and LY gained from LEN/DEX were NOK 247,978 and NOK 198,714,
      respectively, compared to bortezomib. Multiple sensitivity analyses indicated the
      findings were stable. The parameters with the greatest impact were 4-year time
      horizon (NOK 441,457/QALY) and higher bound confidence intervals for PPS (NOK
      118,392). LIMITATIONS: The model analyzed two therapies not compared in head-to
      head trials, and predicted results using an equation incorporating patient-level
      characteristics. It is a limited estimation of the costs and outcomes in a
      Norwegian setting. CONCLUSIONS: The simulation model showed that treatment with
      LEN/DEX leads to greater LYs and QALYs when compared to bortezomib in the
      treatment of rrMM patients. The incremental cost-effectiveness ratio indicated
      treatment with LEN/DEX to be cost-effective and was the basis of the
      reimbursement approval of LEN/DEX in Norway.

PMID- 21892858
TI  - Clinical and economic outcomes in patients with type 2 diabetes initiating
      insulin glargine disposable pen versus exenatide BID.
AB  - OBJECTIVE: To evaluate clinical and economic outcomes in patients with type 2
      diabetes mellitus (T2DM) who failed oral anti-diabetic drug (OAD) therapy and
      initiated either insulin glargine with disposable pen (GLA-P) or exenatide BID
      (EXE). RESEARCH DESIGN AND METHODS: This retrospective study used data from a
      large US-managed care claims database and included adult T2DM patients initiating
      treatment with GLA-P or EXE in 2007 or 2008. Propensity score matching was used
      to control observed baseline differences between treatment groups. Primary study
      end-points included treatment persistence, A1C, healthcare utilization, and
      healthcare costs during the 1-year follow-up period. RESULTS: Two thousand three
      hundred and thirty nine patients were included in the study (GLA-P: 381; EXE:
      1958); 626 patients were in the 1:1 matched cohort (54% male; mean age: 54 years;
      mean A1C: 9.2%). At follow-up, patients in the GLA-P group were significantly
      more persistent in treatment than EXE patients (48% vs 15% in persistence rate
      and 252 vs 144 days in persistence days; both p<0.001). GLA-P patients also had
      significantly lower A1C at follow-up (8.02% vs 8.32%; p=0.042) and greater A1C
      reduction from baseline (-1.23% vs -0.92%; p=0.038). There were no significant
      differences in claims-based hypoglycemia rates and overall diabetes-related
      healthcare utilization and cost. LIMITATIONS: Since this was a retrospective
      analysis, causality of treatment benefits cannot be established. The study was
      specific to two treatments and may not generalize to other models of insulin
      administration. Some of the results, although statistically significant, may not
      be found clinically important. CONCLUSIONS: In a real-world setting among T2DM
      patients who failed to achieve or sustain glycemic goal with OADs, initiation of
      GLA-P instead of EXE may be a more effective option because it was associated
      with greater treatment persistence, greater A1C reduction without a significantly
      higher rate of hypoglycemia, and similar healthcare costs.

PMID- 21892857
TI  - Trajectory analysis of healthcare costs for patients with major depressive
      disorder treated with high doses of duloxetine.
AB  - OBJECTIVE: To examine healthcare cost patterns prior to and following duloxetine
      initiation in patients with major depressive disorder (MDD), focusing on patients
      initiated at or titrated to high doses. RESEARCH DESIGN AND METHODS:
      Retrospective analysis of 10,987 outpatients, aged 18-64 years, who were enrolled
      in health insurance for 6 months preceding and 12 months following duloxetine
      initiation. OUTCOME MEASURES: Repeated measures and pre-post analyses were used
      to examine healthcare cost trajectories before and after initiation of low- (<60
      mg/day), standard- (60 mg/day), and high-dose (>60 mg/day) duloxetine therapy.
      Decision tree analysis was used to identify patient characteristics that might
      explain heterogeneity in economic outcomes following titration to high-dose
      therapy. RESULTS: Low-, standard-, and high-dose duloxetine were initiated for
      29.6%, 60.9%, and 9.5% of patients, respectively. Within 6 months, 13.7% of
      patients had dose increases to > 60 mg/day. Regardless of dose, total costs
      increased prior to and decreased following initiation of treatment. The High
      Initial Dose Cohort had higher costs both prior to and throughout treatment
      compared to the other two cohorts. Following escalation to > 60 mg/day, higher
      medication costs were balanced by lower inpatient costs. Titration to high-dose
      therapy was cost-beneficial for patients with histories of a mental disorder in
      addition to MDD and higher prior medical costs. LIMITATIONS: Conclusions are
      limited by a lack of supporting clinical information and may not apply to
      patients who are not privately insured. CONCLUSIONS: In data taken from insured
      patients with MDD who were started on duloxetine in a clinical setting,
      healthcare costs increased prior to and decreased following initiation of
      therapy. Compared to patients initiated at low- and standard-doses, costs were
      greater prior to and following initiation for patients initiated at high doses.
      Increases in pharmacy costs associated with escalation to high-dose therapy were
      offset by reduced inpatient expenses.

PMID- 21892860
TI  - Editorial board page for "Isotopes in Environmental and Health Studies", Volume
      32, Number 4.
AB  - Abstract This is a scanned image of the original Editorial Board page(s) for this
      issue.

PMID- 21892859
TI  - Use of drospirenone/ethinyl estradiol (DRSP/EE) among women with acne reduces
      acne treatment-related resources.
AB  - BACKGROUND AND OBJECTIVE: Acne is a common dermatologic condition that extends
      into middle age, particularly among women, and is associated with substantial
      healthcare resource utilization. Drospirenone (DRSP), a synthetic progestin, has
      anti-androgenic activity, and women using DRSP 3.0 mg/ethinyl estradiol (EE) 0.02
      mg as a 24/4 regimen (DRSP/EE-24/4) for contraception also may use it for
      treatment of moderate acne. The study used a US national healthcare database to
      assess acne-related healthcare resource utilization among women aged 18-45 years
      before (pre-index) and after (post-index) initiation of DRSP/EE-24/4. METHODS:
      Resource utilization and costs were evaluated by age group (18-25, 26-35, or 36
      45 years) and by type of acne medication (systemic antibiotic, topical, or anti
      androgen). RESULTS: Data for 1340 women were evaluated. Overall, drug costs,
      medical costs, and total costs were decreased by 38%, 37%, and 37%, respectively
      (p<0.0001 for all) between the pre-index and post-index periods; significant
      differences were evident across age groups and acne medication categories. Total
      costs were significantly decreased for patients (41%) and healthcare plans (36%;
      p<0.0001 for both) overall and across age groups and drug classes. Acne-related
      claims and number of days using acne medication were reduced (by 37% each;
      p<0.0001 for both). STUDY LIMITATIONS: The study was retrospective in design and
      had a limited follow-up period. Database limitations restricted assessment of
      medication compliance and adherence. CONCLUSION: DRSP/EE-24/4 use was associated
      with substantial reductions in acne-related healthcare resource utilization, and
      reductions occurred regardless of age or type of acne medication. DRSP/EE-24/4
      therefore represents a cost-effective option for the treatment of acne among
      women using DRSP/EE-24/4 for oral contraception.

PMID- 21892861
TI  - Functional inhomogeneities in interstitial lung disease, assessed using
      (16)o(18)o.
AB  - Abstract We investigated the contribution of diffusion limitation and functional
      inhomogeneities to the impairment of pulmonary oxygen (O(2)) transfer in
      interstitial lung disease (ILD). Analyses of (16)O(18)O/(16)O(2) ratios were
      performed on expiratory gas mixtures obtained from 6 ILD patients and 6 healthy
      humans at rest, applying respiratory mass spectrometry. We assessed O(2)
      transport by using the overall fractionation factor of respiration (alpha(0))
      which is predicted to increase in the case of diffusion limitation. alpha(0) was
      reduced in patients (1.0065+/-3.10(-4)) when compared to the value for healthy
      subjects (1.0071+/-7.10(-4), P <0.05), pointing away from a diffusion limitation
      of O(2) transport. On the basis of a two-compartment model we interpreted our
      findings by assuming an unequal distribution of diffusion and convective O(2)
      transport in the pulmonary gas exchange of the patients.

PMID- 21892862
TI  - Rapid, Sensitive and Highly Selective (15)N Analysis of (15)N Enriched Nitrite in
      Water Samples and Soil Extracts by Nitric Oxide Production and CF-QMS
      Measurement.
AB  - Abstract Nitrite is a very important intermediate in many microbiological N
      transformations in soils and water. The stable isotope (15)N is often used to
      investigate these processes. The determination of (15)N in low concentrations of
      nitrite in the presence of large concentrations of nitrate is very difficult.
      Methods used so far for the isotope analysis of nitrite are unsatisfactory,
      because the nitrite must be calculated as the difference between nitrate plus
      nitrite and nitrate alone. More useful are mehods by which the nitrite is
      selectively converted into a chemical form that is suitable for (15)N analysis
      and that is free from interference from other N species, particularly nitrate.
      Using this principle in the present study we developed a method where the nitrite
      is reduced to nitric oxide by iodide in acid medium. This reaction is fast and
      quantitative, and the (15)N abundance of NO can be precisely measured by
      continuous flow mass spectrometry. This method is used for samples from tracer
      experiments with artificially enriched nitrogen 15. Therefore, the use of simple
      quadrupole mass spectrometers directly linked to the reaction unit is possible
      with sufficient precision (Reaction-Continuous Flow Quadrupole Mass Spektrometry
      RCFQMS). Using the technique developed sample volumes up to 10ml containing at
      least 1.0 MUg nitrite-N (0, 1 MUg/ml) with a (15)N abundance of ? 0.42 at.% gave
      a precision of RSD ? +/- 3%.

PMID- 21892863
TI  - Gel-electrophoresis and subsequent optical emission (15)n analysis to identify
      (15)n-labelled protein fractions.
AB  - Abstract A combined procedure to detect of (15)N/(14)N isotope ratios by emission
      spectrometric analysis after starch gel-electrophoresis was developed. (15)N
      labelled proteins of human serum were used to optimise this method.
      Electrophorised gel slices with protein fractions were directly digested for
      subsequent isotope analysis. This method is proposed for use in routine analysis
      for clinical application.

PMID- 21892864
TI  - Methodical studies for d/h-isotope analysis - a new technique for the direct
      coupling of sample preparation to an irms.
AB  - Abstract A new technique for the sample preparation and direct coupling to an
      Isotope Ratio Mass Spectrometer (IRMS) for the D/H-determination is described. 1
      MUl size samples of water are injected and reduced with chromium metal in a novel
      reaction furnace. The hydrogen gas flows directly into the IRMS and is analysed
      (standard/sample comparison). The reproducibility is about 1 %. The accuracy of
      the technique was proven by means of the IAEA-standard waters V-SMOW, GISP, SLAP.

PMID- 21892865
TI  - Radiotracer measurement of the volatilization of organic trace constituents from
      water.
AB  - Abstract The mass-transfer coefficient for the volatilization of organic
      microconstituents from water can be determined by laboratory radiotracer
      experiments. Formulation and practical aspects are considered and illustrated by
      the example of a 5.10(-7) M solution of monochlorobenzene.

PMID- 21892866
TI  - Isotope anomalies of carbon, hydrogen and nitrogen in peat from the area of the
      tunguska cosmic body explosion (1908).
AB  - Abstract Peat profiles from the area of the Tunguska explosion epicentre indicate
      significant carbon and hydrogen isotopic effects which are clearly associated
      with the zone of the 1908 "catastrophe", and which cannot be attributed to any
      known terrestrial processes. We explain them with the presence of
      extraterrestrial matter similar to carbonaceous chondrites or, more probably, to
      cometary matter. Initial data on nitrogen content and its isotope composition are
      consistent with the assumption of acid rainfall following the passage and
      explosion of the Tunguska cosmic body, as is known to have occurred during the
      Cretaceous-Tertiary boundary.

PMID- 21892867
TI  - Komplexe Untersuchungen zur quartaren Eisstausee-Entwicklung in
      Mitteldeutschland.
AB  - Abstract Geological-sedimentological (grain size, micromorphology, varve
      correlation) and geochemical (stable isotopes: (18)O/(16)O,(13)C/(12)C)
      investigations with ice-dammed lake sediments of the Dehlitz-Leipzig varved clay
      enable to elucidate in detail the palaeosedimentologic and palaeoclimatic
      conditions in the surrounding of the Elsterian Scandinavian inland-ice sheet a
      relatively short time before its maximum extension in Central Europe took place.
      For the space of time between formation of the ice-dammed glacial lake and its
      run-over by Scandinavian inland-ice sheet the obtained results allow to
      distinguish at least four evolutionary phases. Regarding the palaeosedimentologic
      relations in the ice-dammed glacial lake these four phases are characterized by
      differences in the dynamics of sediment input, suspension density within the
      water body and existence/absence of stagnation events with syngenetic formation
      of carbonates under anoxic conditions. During the formation of glacial varves the
      obtained data seem to support the existence of small seasonal differences which
      can be due to very cold, long winter- and short, cool summer periods. In this way
      the time of the first Elsterian glacial maximum, reflected by the varved clays,
      can be classified as a typical glacial climatic period.

PMID- 21892868
TI  - Mineral- und heilwasser in sachsen - eine isotopenanalytische charakterisierung.
AB  - Abstract The groundwaters studied and labelled as mineral water were "natural
      mineral waters" for bottled waters and "natural curative waters" for heal
      therapeutical applications. They were characterized either by a specific
      mineralization or their suitability for balneology. To reveal the actual
      hydrological situation isotope investigations using (2)H, (18)O, (3)H, (12)C and
      (14)C (DIC) and (34)S (sulphate) were included in a study describing samples of
      24 mineral water deposits in Saxonia. The water was classified into 4
      hydrochemical types of genesis. Due to different hydrogeological and
      hydrochemical situations widely scattered isotope ratios were measured. Most of
      the investigated mineral waters are containing at least parts of younger waters
      (with residence times less than about 40 years). Correlations between chemical
      composition and the tritium content could be observed within different springs
      from the areas Bad Brambach, Bad Elster and Burkhardswalde. Strong variations in
      delta(34)S were found in samples with low sulphate content, showing different
      sulphur sources, as well as microbiological reactions. On the other hand mineral
      waters from Bad Brambach and Bad Elster show nearly the same delta(34)S value of
      about 60/00 CDT despite beeing of a different chemical type. The delta(13)C
      values between -22 and -2.2y PDB are related to different sources of CO(2).

PMID- 21892869
TI  - Isotopic composition of sulfates: similarities - differences - misleadings.
AB  - Abstract In the hydrosphere sulfates of the following origin may exist: (1)
      evaporitic; they come from the leaching of sulfate rocks, (2) biological, formed
      by sulfur-oxidizing bacteria and (3) anthropogenic, which get into water with
      wastes, fertilizers or acid rains. Chemical analyses may reveal sulfates in
      water, but their origin cannot be assessed by means of chemical analysis. The
      sulfates of various origin may differ in their isotopic compositions. However,
      sometimes we can observe the similarity of delta(34)S of sulfates whose origin
      was entirely different. This similarity may be so suggestive that it could be
      misleading. This paper presents patterns of completely different sulfates whose
      delta(34)S are similar, though they have nothing in common. Other tables present
      patterns of sulfates whose origin is similar or even the same but their
      delta(34)S are characterized by great variety. All of the isotopic data presented
      in the tables were specially chosen from some of the results of the studies of
      the sulfates in waters in Poland. Isotopes techniques are becoming more popular
      and are useful for studies in many fields. These patterns may be a warning
      against drawing hasty conclusions from the results of delta-measuring.

PMID- 21892870
TI  - Effect of calcium ions on the irradiation induced inactivation of cellulase.
AB  - Abstract The activity of cellulase irradiated at various temperatures was
      examined as a function of irradiation dose. The effect of calcium ions in
      radiation inactivation of cellulase at irradiation temperature of 30 degrees C
      was studied by using calcium sulfate. The calcium ions have a protective ability
      against radiation caused inactivation of cellulase by scavenging species such as
      OH(-) formed by irradiation of cellulase aqueous solution, in which the effective
      concentration range of the calcium ions was ~ 10(-3) M. The calcium ions do not
      act for the heat inactivation of the enzyme and the enzyme hydrolysis of filter
      paper or chaff as an activator because the calcium ions do not associate with the
      enzyme to form a calcium ion-enzyme complex.

PMID- 21892871
TI  - Conference report.

PMID- 21892873
TI  - Erratum.

PMID- 21892872
TI  - A review of: "Isotopes in Water Resources Management".
AB  - Abstract Proceedings of the International Symposium, organized by the IAEA, in co
      operation with UNESCO, Vienna, 20-24 March 1995. Vol. 1 (ISBN 92-0-105595-1) and
      Vol. 2 (ISBN 92-0-100796-5), edited by IAEA, Vienna, Austria, March 1996.

PMID- 21892874
TI  - Physiology and pathophysiology of selectins, integrins, and IgSF cell adhesion
      molecules focusing on inflammation. A paradigm model on infectious endocarditis.
AB  - The development of adhesion bonds, either among cells or among cells and
      components of the extracellular matrix, is a crucial process. These interactions
      are mediated by some molecules collectively known as adhesion molecules (CAMs).
      CAMs are ubiquitously expressed proteins playing a central role in controlling
      cell migration, proliferation, survival, and apoptosis. Besides their key
      function in physiological maintenance of tissue integrity, CAMs play an eminent
      role in various pathological processes such as cardiovascular disorders,
      atherogenesis, atherosclerotic plaque progression and regulation of the
      inflammatory response. CAMs such as selectins, integrins, and immunoglobulin
      superfamily take part in interactions between leukocyte and vascular endothelium
      (leukocyte rolling, arrest, firm adhesion, migration). Experimental data and
      pathologic observations support the assumption that pathogenic microorganisms
      attach to vascular endothelial cells or sites of vascular injury initiating
      intravascular infections. In this review a paradigm focusing on cell adhesion
      molecules pathophysiology and infective endocarditis development is given.

PMID- 21892876
TI  - Pharmacokinetic profile of 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside in
      mice after oral administration of Polygonum multiflorum extract.
AB  - CONTEXT: Stilbene glycoside (2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside)
      is a main bioactive component of Polygonum multiflorum, a traditional Chinese
      medicine (TCM) commonly used in clinic for anti-aging treatment. Its medicinal
      activities, such as anti-oxidation, anti-inflammation and endothelial protection,
      have been extensively studied, but its pharmacokinetic property is still unclear.
      OBJECTIVE: A pharmacokinetic study was undertaken to quantitatively determine P.
      multiflorum stilbene glycoside (PM-SG) in mouse plasma after oral administration
      of 100 mg/kg P. multiflorum extract. MATERIALS AND METHODS: A sensitive reversed
      phase high-performance liquid chromatography (RP-HPLC) coupled with liquid-liquid
      phase extraction method was employed for this study. Pharmacokinetic parameters
      of PM-SG were determined in mice applying both compartmental and non
      compartmental analyses. RESULTS AND DISCUSSION: The calibration curve for PM-SG
      in the plasma was linear (r(2) > 0.99) over the range of 0.66 to 56.40 MUg/ml,
      and the concentration-time curve was plotted with the maximum concentration
      (C(max)) and time to reach maximum concentration (T(max)) of 29.62 MUg/ml and 60
      min, respectively. The intra- and inter-day variations were less than 3% for
      relative standard deviation (RSD) and relative error (RE), with a good recovery
      of more than 97% (RSD <3%). All pharmacokinetic parameters estimated by
      compartmental and non-compartmental models reached a same conclusion that PM-SG
      was rapidly absorbed and widely distributed throughout the body with a great
      efficiency of utility, followed by quick elimination and clearance. CONCLUSIONS:
      This was the first report on determination of the pharmacokinetic profile of PM
      SG in mice after oral administration. The result may provide a meaningful basis
      for evaluating the clinical applications of such a bioactive compound from herbal
      medicines.

PMID- 21892875
TI  - Evaluation of bioactivity and pharmacokinetic characteristics of PEGylated
      P.pastoris-expressed erythropoietin.
AB  - High costs of production and relatively short serum half-life of mammalian cell
      derived recombinant human erythropoietin (rHuEpo) necessitate finding and
      developing superior hosts/technologies for more efficient production of longer
      acting erythropoietic agents. With these aims, we provide the first report on
      reductive alkylation of low-cost P.pastoris-expressed rHuEpo (PPEpo) with PEG
      aldehyde. The PCR-amplified cDNA of native rHuEpo was cloned into the pPICZalphaA
      vector and transformed into the yeast Pichia pastoris. The best expressing
      transformant was selected and employed for secreted-expression of PPEpo using the
      standard protocols. Purified PPEpo was N-terminally PEGylated with 20-kDa mPEG
      propionaldehyde in a low pH (5) condition. The in vitro and in vivo biological
      activities of purified mono-PEGylated PPEpo was evaluated by the UT-7 cells
      proliferation assay and normocythaemic mice assay, respectively. Pharmacokinetic
      parameters were determined following intravenous administration of Epo proteins
      in rabbits. While PPEpo showed a higher in vitro bioactivity compared to rHuEpo,
      no in vivo efficiency was determined for PPEpo. However, the in vivo activity of
      PEG-PPEpo conjugate was comparable to that of rHuEpo. Pharmacokinetic studies
      showed that the terminal half-life and mean residence time of PEG-PPEpo were
      increased approximately 4-fold and 6.5-fold respectively, compared with those of
      PPEpo. The results indicate that N-terminal PEGylation of Pichia-expressed Epo
      could be considered as a promising approach for generating cost-effective and
      long-acting erythropoiesis-stimulating agents.

PMID- 21892877
TI  - Feeding intolerance in preterm infants. How to understand the warning signs.
AB  - It is essential to start enteral nutrition early to preterm infants by giving
      small amounts of milk (preferably human milk) to ensure that metabolic
      homeostasis is kept stable and to limit postnatal growth retardation. Increasing
      feeding volumes to reach "full enteral feeding" is limited by individual feeding
      tolerance. Feeding intolerance is extremely common in premature infants. The most
      frequent signs of a suspect feeding intolerance are the presence of gastric
      residuals, abdominal distension and the onset of crises of apnea/bradycardia.
      Gastric residuals are probably a benign consequence of delayed gut maturation and
      motility in VLBW infants and there are no established normal standards. When
      gastric aspirates occur isolated they should not immediately induce the
      neonatologist to withhold feeding. Gastric residual becomes more important when
      accompanied by other warning signs, such as bilious vomiting, abdominal
      distension, abdominal wall erythema or ecchymosis, gross or occult blood in the
      stool, apnoea, bradycardia and temperature instability. Nutrition protocols in
      preterm infants must take caution when starting and increasing enteral feeding,
      and pay proper, but not excessive, attention to early signs of food intolerance.

PMID- 21892878
TI  - BPD: old and new problems.
AB  - Bronchopulmonary dysplasia (BPD) is still one of the main long term complication
      of preterm birth, and it is the most common chronic respiratory disease in
      infants. Due to advances in perinatal care and neonatal respiratory therapy the
      clinical characteristics and the natural history of infants affected by BPD have
      widely changed in the last decades. The sever presentation of the old form of BPD
      has been replaced by a milder clinical form, without or with mild respiratory
      distress syndrome in the first days of life, that responds rapidly to surfactant
      therapy and instead requires prolonged ventilator support because of poor
      respiratory effort. "Old" and "new" BPD, are also histologically different, being
      two morphologic outcomes of variable combinations of factors injuring lungs of
      differing maturity. New BPD is characterized by diffusely reduced alveolar
      development, with airway injury, inflammation and fibrosis that are usually
      milder than in old form. Such "new" form of BPD is interpreted as a developmental
      disorder. The development of BPD is a multifactorial process with pathogenesis
      being linked to immature lung tissue, barotrauma and volutrauma resulting from
      mechanical ventilation, oxidant injury, and proinflammatory mediators.and
      inflammatory regulation may also have a role in the development of the new form.
      There is growing evidence that BPD results from an imbalance between
      proinflammatory and anti-inflammatory mechanisms, with a persistent imbalance
      that favors proinflammatory mechanisms. Reduction of the incidence and severity
      of BPD may be possible through a reduction of the amount of injury induced by
      respiratory support interventions.

PMID- 21892880
TI  - The fate of 4-hydroxycarbazole metabolite: metabolism and carcinogenicity
      assessment of a beta-adrenergic receptor modulator containing carbazole
      structure.
AB  - LY377604 has a potential to form 4-hydroxycarbazole, which was reported in the
      literature as a mutagen. This safety concern led to our investigation of the
      metabolism and carcinogenicity of LY377604. In in vitro studies with LY377604, 4
      hydroxycarbazole was detected in the presence of liver microsomes prepared from
      different species. When incubated with liver slices, only the conjugate of 4
      hydroxycarbazole was detected. Subsequent in vivo radio-labelled studies were
      conducted to characterise the formation of 4-hydroxycarbazole from LY377604. Free
      4-hydroxycarbazole was not detected in vivo, but the O-glucuronide conjugate was
      identified as a minor metabolite in urine samples, representing 0.2% and 0.9% of
      the radioactive dose in rats and monkeys. The low level of circulating 4
      hydroxycarbazole glucuronide conjugate was also detected in plasma. LY377604 was
      negative in all genetic toxicology assays and was not associated with tumour
      induction in a 6-month carcinogenicity study using RasH2+/- mouse model. The
      exposure to free 4-hydroxycarbazole was not measurable after one dose and was
      about 0.1%-0.2% of the parent exposure at the end of the 6-month study. These
      data suggested that 4-hydroxycarbazole was formed as a minor metabolite in vivo,
      but it was primarily conjugated and excreted in urine as the glucuronide
      conjugate. The absence of tumours in the carcinogenicity study combined with the
      exposure data suggested that the low level of free 4-hydroxycarbazole did not
      represent a carcinogenic risk.

PMID- 21892879
TI  - Interspecies scaling and prediction of human clearance: comparison of small- and
      macro-molecule drugs.
AB  - Human clearance prediction for small- and macro-molecule drugs was evaluated and
      compared using various scaling methods and statistical analysis. Human clearance
      is generally well predicted using single or multiple species simple allometry for
      macro- and small-molecule drugs excreted renally. The prediction error is higher
      for hepatically eliminated small-molecules using single or multiple species
      simple allometry scaling, and it appears that the prediction error is mainly
      associated with drugs with low hepatic extraction ratio (Eh). The error in human
      clearance prediction for hepatically eliminated small-molecules was reduced using
      scaling methods with a correction of maximum life span (MLP) or brain weight
      (BRW). Human clearance of both small- and macro-molecule drugs is well predicted
      using the monkey liver blood flow method. Predictions using liver blood flow from
      other species did not work as well, especially for the small-molecule drugs.

PMID- 21892881
TI  - Pharmacokinetic and pharmacodynamic properties of carvedilol in fructose
      hypertensive rats.
AB  - Cardiovascular effects and pharmacokinetics of carvedilol were assessed in
      fructose-fed rats using pharmacokinetic-pharmacodynamic (PK-PD) modeling. Male
      Sprague-Dowley rats were randomly assigned to receive tap water (C rats) or
      fructose solution (10% w/v) (F rats) during 6 weeks. Effects of carvedilol (1-3
      mg/kg i.v.) on blood pressure, heart rate and blood pressure variability were
      recorded. Carvedilol plasma pharmacokinetics was studied by traditional blood
      sampling. Relationship between carvedilol concentrations and their hypotensive
      and bradycardic effects was established by PK-PD modeling. Vascular sympatholytic
      activity of carvedilol was assessed by estimation of drug effects on low
      frequency blood pressure variability using spectral analysis. A greater volume of
      distribution and clearance of S-carvedilol compared to R-enantiomer was found in
      both experimental groups. Although PK-PD properties of S-carvedilol chronotropic
      effect were not altered in F rats, hypertensive rats showed greater efficacy to
      the carvedilol hypotensive response after administration of the higher dose. A
      similar potency of carvedilol to inhibit sympathetic vascular activity was found
      in F rats. Carvedilol showed enantioselective pharmacokinetic properties with
      increased distribution in F rats compared with normotensive animals. An enhanced
      hypotensive activity of carvedilol was found in F rats compared with C rats,
      which is not related to enhance sympatholytic activity.

PMID- 21892882
TI  - Maternal omega-3 fatty acid supplementation protects against lipopolysaccharide
      induced white matter injury in the neonatal rat brain.
AB  - OBJECTIVES: Periventricular leukomalacia (PVL) is the predominant form of brain
      injury in premature infants, and no specific treatment currently exists for this
      condition. We have evaluated whether maternal omega-3 fatty acid (omega3 FA)
      treatment reduces endotoxin-induced PVL in the developing rat brain. METHODS:
      Wistar rats with dated pregnancies were fed a standard diet or a diet enriched in
      omega3 FA (70% docosahexaenoic acid + 30% eicosapentaenoic acid mixture) during
      gestation. Intraperitoneal injection of lipopolysaccharide (LPS) was administered
      consecutively on the 18th and 19th embryonic days to establish the endotoxin
      induced PVL rat model. The animals were divided into four groups: (i) control,
      (ii) PVL, (iii) PVL+low-dose omega3 FA and (iv) PVL+high-dose omega3 FA. At day
      P7, apoptosis and hypomyelination in periventricular white matter were evaluated
      by immunohistochemical assessments. RESULTS: High-dose maternal omega3 FA
      treatment reduced brain weight loss. Maternal omega3 FA treatment given either in
      low or high doses greatly decreased caspase-3 immunoreactivity and increased
      myelin basic protein immunoreactivity, indicating a decrease in apoptosis and
      hypomyelination. CONCLUSION: Considering that no specific treatment is available
      for PVL, maternal omega3 FA supplementation may provide a nutritional strategy to
      limit periventricular white matter damage caused by infections during pregnancy.

PMID- 21892883
TI  - Patent ductus arteriosus: patho-physiology, hemodynamic effects and clinical
      complications.
AB  - During fetal life, patent arterial duct diverts placental oxygenated blood from
      the pulmonary artery into the aorta by-passing lungs. After birth, decrease of
      prostacyclins and prostaglandins concentration usually causes arterial duct
      closure. This process may be delayed, or may even completely fail in preterm
      infants with arterial duct still remaining patent. If that happens, blood flow by
      pass of the systemic circulation through the arterial duct results in pulmonary
      overflow and systemic hypoperfusion. When pulmonary flow is 50% higher than
      systemic flow, a hemodynamic "paradox" results, with an increase of left
      ventricular output without a subsequent increase of systemic output. Cardiac
      overload support neuro-humoral effects (activation of sympathetic nervous system
      and renin-angiotensin system) that finally promote heart failure. Moreover,
      increased pulmonary blood flow can cause vascular congestion and pulmonary edema.
      However, the most dangerous effect is cerebral under-perfusion due to diastolic
      reverse-flow and resulting in cerebral hypoxia. At last, blood flow decreases
      through the abdominal aorta, reducing perfusion of liver, gut and kidneys and may
      cause hepatic failure, renal insufficiency and necrotizing enterocolitis.
      Conclusions Large patent arterial duct may cause life-threatening multi-organ
      effects. In pre-term infant early diagnosis and timely effective treatment are
      cornerstones in the prevention of cerebral damage and long-term multi-organ
      failure.

PMID- 21892884
TI  - Tangible words are recognized faster: the grounding of meaning in sensory and
      perceptual systems.
AB  - Sensory experience rating (SER), a new variable motivated by the grounded
      cognition framework of conceptual processing (e.g., Barsalou, 2008 ), indexes the
      degree to which a word evokes sensory/perceptual experiences. In the present
      study, SERs were collected for over 2,850 words. While SER is correlated with
      imageability, age of acquisition, and word frequency, the latter variables (along
      with seven others) account for less than 30% of the variance in SER. Reanalyses
      of two large-scale studies demonstrate that SER significantly predicts lexical
      decision times when other established predictor variables are statistically
      controlled. These results suggest that conceptual processing is grounded in
      sensory systems. Additionally, a major benefit of this variable is that it allows
      psycholinguistic researchers to examine semantic-perceptual links for all word
      classes with a single rating.

PMID- 21892886
TI  - Lost papers (2).

PMID- 21892887
TI  - Tritium in precipitation of Vostok (Antarctica): conclusions on the tritium
      latitude effect.
AB  - During the Antarctic summer of 1985 near the Soviet Antarctic station Vostok,
      firn samples for tritium measurements were obtained down to a depth of 2.40 m.
      The results of the tritium measurements are presented and discussed. Based on
      this and other data, conclusions regarding the tritium latitude effect are
      derived.

PMID- 21892888
TI  - Environmental studies in Antarctica on the basis of tritium and radiocarbon
      measurements.
AB  - In 1975 and 1977, samples from snow, firn, atmospheric CO(2), plants, and penguin
      guano were collected near the Soviet Antarctic research station Molodezhnaya. The
      results of tritium, deuterium, oxygen-18, (13)C, and (14)C measurements are
      discussed. From the tritium, deuterium, and (18)O measurement results of a firn
      profile at the Hays glacier, a value of the accumulation rate of 30 g water per
      cm 2 and year could be evaluated. By means of (14)C dating, the age of penguin
      breeding places was determined to be 1500 +/- 500 years. (14)C data from
      atmospheric CO(2) and plants are discussed in terms of the age of the plants.

PMID- 21892889
TI  - Isotope variations of hydrogen, carbon and nitrogen in florae from the
      Schirmacher Oasis, East Antarctica.
AB  - Comparative biochemical and isotope-chemical investigations of cosmopolitical
      plants open up ways of obtaining parameters from different parts of the Earth
      which are characterised by variations in the habitat due to different
      environments. As an Antarctic oasis, the Schirmacher Oasis disposes of adequate
      favourable ecological conditions for the growth of lower plants. In the present
      paper, results of isotope studies of lichens, mosses and algae of the Schirmacher
      Oasis are given and peculiarities of the habitats which influence the isotope
      contents of the plants are discussed.

PMID- 21892890
TI  - Identification of the nitrate contamination sources of the Brusselian sands
      groundwater body (Belgium) using a dual-isotope approach.
AB  - Isotopic fingerprinting is an advanced technique allowing the classification of
      the nitrate source pollution of groundwater, but needs further development and
      validation. In this study, we performed measurements of natural stable isotopic
      composition of nitrate ((15)N and (18)O) in the groundwater body of the Brussels
      sands (Belgium) and studied the spatial and temporal dynamics of the isotope
      signature of this aquifer. Potential nitrogen sources sampled in the region had
      isotopic signatures that fell within the corresponding typical ranges found in
      the literature. For a few monitoring stations, the isotopic data strongly suggest
      that the sources of nitrate are from mineral fertiliser origin, as used in
      agriculture and golf courses. Other stations suggest that manure leaching from
      unprotected stockpiles in farms, domestic gardening practices, septic tanks and
      probably cemeteries contribute to the nitrate pollution of this groundwater body.
      For most monitoring stations, nitrate originates from a mixing of several
      nitrogen sources. The isotopic signature of the groundwater body was poorly
      structured in space, but exhibited a clear temporal structure. This temporal
      structure could be explained by groundwater recharge dynamics and cycling process
      of nitrogen in the soil-nitrogen pool.

PMID- 21892891
TI  - Reliability of stable carbon and oxygen isotope compositions of pedogenic needle
      fibre calcite as environmental indicators: examples from Western Europe.
AB  - Stable carbon and oxygen isotope analyses were conducted on pedogenic needle
      fibre calcite (NFC) from seven sites in areas with roughly similar temperate
      climates in Western Europe, including the Swiss Jura Mountains, eastern and
      southern France, northern Wales, and north-eastern Spain. The delta(13)C values (
      12.5 to-6.8 0/00 Vienna Pee Dee Belemnite (VPDB)) record the predominant C(3)
      vegetation cover at the sites. A good correlation was found between mean monthly
      climatic parameters (air temperature, number of frost days, humidity, and
      precipitation) and delta(18)O values (-7.8 to-3.40/00 VPDB) of all the NFC.
      Similar seasonal variations of delta(18)O values for monthly NFC samples from the
      Swiss sites and those of mean monthly delta(18)O values of local precipitation
      and meteorological data point out precipitation and preferential growth/or
      recrystallisation of the pedogenic needle calcite during dry seasons. These
      covariations indicate the potential of stable isotope compositions of preserved
      NFC in fossil soil horizons as a promising tool for palaeoenvironmental
      reconstructions.

PMID- 21892892
TI  - Stable isotopes determination in some Romanian fruit juices.
AB  - The characterisation of 45 Romanian single-strength fruit juices (apples, pears,
      plums and grapes) collected from different Transylvanian areas by means of stable
      isotope approach are presented and discussed in this study. We measured
      (2)H/(1)H, (18)O/(16)O ratios from water juice and (13)C/(12)C from pulp and
      compared these results with those already reported in the literature for single
      strength juices, in order to see how the geographical and climatic conditions of
      Transylvania and the meteorological peculiarities of the year 2010 influence the
      isotopic composition of the investigated fruit juices. The delta(13)C mean values
      that we found for apple pulp picked up from different Transylvanian areas show
      slight differences, probably due to the environmental conditions of the plants.
      No significant correlation either between the variety of apple or the
      geographical origin and delta(13)C value was established.

PMID- 21892893
TI  - Pentecostalism and AIDS treatment in Mozambique: creating new approaches to HIV
      prevention through anti-retroviral therapy.
AB  - Pentecostal fervor has rapidly spread throughout central and southern Mozambique
      since the end of its protracted civil war in the early 1990s. In the peri-urban
      bairros and septic fringes of Mozambican cities African Independent Churches
      (AICs) with Pentecostal roots and mainstream Pentecostals can now claim over half
      the population as adherents. Over this same period another important phenomenon
      has coincided with this church expansion: the AIDS epidemic. Pentecostalism and
      HIV have travelled along similar vectors and been propelled by deepening
      inequality. Recognising this relationship has important implications for HIV/AIDS
      prevention and treatment strategies. The striking overlap between high HIV
      prevalence in peri-urban populations and high Pentecostal participation suggests
      that creative strategies, to include these movements in HIV/AIDS programming, may
      influence the long-term success of HIV care and the scale-up of anti-retroviral
      treatment (ART) across the region. The provision of ART has opened up new
      possibilities for engaging with local communities, especially Pentecostals and
      AICS, who are witnessing the immediate benefits of ARV therapy. Expanded
      treatment may be the key to successful prevention as advocates of a comprehensive
      approach to the epidemic have long argued.

PMID- 21892894
TI  - Ideologies of Black churches in New York City and the public health crisis of HIV
      among Black men who have sex with men.
AB  - Black men who have sex with men (MSM) are disproportionately affected by HIV and
      AIDS in New York City (NYC). Black churches in NYC have a history of engaging in
      community mobilisation; however, research suggests that churches play a role in
      promoting stigma against Black MSM, which impedes prevention efforts. The goal of
      this study was to explore church ideologies surrounding sexuality and health, and
      the relationship of these ideologies to church mobilisation in response to
      HIV/AIDS among Black MSM. We conducted interviews and focus groups with pastors
      and parishioners at Black churches in NYC. Three prominent themes were
      identified: (1) 'Love the sinner, hate the sin'--distinguishing behaviour and
      identity; (2) 'Don't ask, don't tell'--keeping same-sex behaviour private; and
      (3) 'Your body is a temple'--connecting physical and spiritual health. We discuss
      the implications of these ideologies for church mobilisation and HIV prevention
      efforts. In doing so, we pay close attention to how ideologies may both impede
      and facilitate church dialogue around sexuality and heightened responses to the
      HIV crisis affecting Black MSM.

PMID- 21892895
TI  - Pharmacokinetic evaluation of pramipexole.
AB  - INTRODUCTION: Immediate-release (IR) pramipexole dihydrochloride is indicated for
      the treatment of signs and symptoms of idiopathic Parkinson's disease (PD). It is
      administered alone (without levodopa) or in combination with levodopa, during the
      entire progress of the disease, up to an advanced stage. Currently, it is also
      indicated for the treatment of moderate-to-severe primary restless legs syndrome
      (RLS). An extended-release (ER) formulation of pramipexole has been developed to
      allow a once-daily administration and to provide more stable dopaminergic
      stimulation in PD patients. AREAS COVERED: This review summarizes the overall
      pharmacokinetic profile of pramipexole for both the IR and ER formulations. Also
      discussed are the clinically relevant determinants of pramipexole peripheral
      pharmacokinetics and the potential role of genetic and clinical determinants in
      drug efficacy. EXPERT OPINION: Pramipexole is a non-ergot agonist with selective
      affinity for dopamine receptors of the D2 subfamily, in particular D3.
      Pramipexole has a very low affinity for serotoninergic 5-HT2A and 5-HT2B
      receptors, as well as D1-type receptors. Furthermore, it does not carry the risk
      to induce valvular heart disease or pulmonary and retroperitoneal fibrosis, seen
      with long-term use of the ergot-derived dopamine agonists. The recent
      introduction of a once-daily formulation poses significant advantages for
      patients, reflected by relatively stable plasma levels. The most obvious benefit
      is convenience of use and better adherence to treatment schedule. Additional
      advantages could include the opportunity to provide more continuous drug delivery
      in a fashion that could help minimize dyskinesia risk, if the drug is used early
      in the disease course.

PMID- 21892896
TI  - Central role of mitochondria in drug-induced liver injury.
AB  - A frequent mechanism for drug-induced liver injury (DILI) is the formation of
      reactive metabolites that trigger hepatitis through direct toxicity or immune
      reactions. Both events cause mitochondrial membrane disruption. Genetic or
      acquired factors predispose to metabolite-mediated hepatitis by increasing the
      formation of the reactive metabolite, decreasing its detoxification, or by the
      presence of critical human leukocyte antigen molecule(s). In other instances, the
      parent drug itself triggers mitochondrial membrane disruption or inhibits
      mitochondrial function through different mechanisms. Drugs can sequester coenzyme
      A or can inhibit mitochondrial beta-oxidation enzymes, the transfer of electrons
      along the respiratory chain, or adenosine triphosphate (ATP) synthase. Drugs can
      also destroy mitochondrial DNA, inhibit its replication, decrease mitochondrial
      transcripts, or hamper mitochondrial protein synthesis. Quite often, a single
      drug has many different effects on mitochondrial function. A severe impairment of
      oxidative phosphorylation decreases hepatic ATP, leading to cell dysfunction or
      necrosis; it can also secondarily inhibit beta-oxidation, thus causing steatosis,
      and can also inhibit pyruvate catabolism, leading to lactic acidosis. A severe
      impairment of beta-oxidation can cause a fatty liver; further, decreased
      gluconeogenesis and increased utilization of glucose to compensate for the
      inability to oxidize fatty acids, together with the mitochondrial toxicity of
      accumulated free fatty acids and lipid peroxidation products, may impair energy
      production, possibly leading to coma and death. Susceptibility to parent drug
      mediated mitochondrial dysfunction can be increased by factors impairing the
      removal of the toxic parent compound or by the presence of other medical
      condition(s) impairing mitochondrial function. New drug molecules should be
      screened for possible mitochondrial effects.

PMID- 21892897
TI  - Nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae,
      Moraxella catarrhalis, and Alloiococcus otitidis in young children in the era of
      pneumococcal immunization, Taiwan.
AB  - We applied a multiplex polymerase chain reaction (PCR) and culture to detect
      Streptococcus pneumoniae and detected 3 other respiratory pathogens--Haemophilus
      influenzae, Moraxella catarrhalis, and Alloiococcus otitidis--simultaneously by
      PCR, in the nasopharynx of 386 children aged under 5 y. S. pneumoniae was the
      most common pathogen carried by children in all age groups, with the rate ranging
      from 15.8% in children aged 3-4 y to 28.6% in children aged 2-3 y. H. influenzae
      and M. catarrhalis showed similar carriage rates across all the age groups. Only
      2 young children (0.5%) carried A. otitidis. Higher carriage of S. pneumoniae was
      found in children who had not received the heptavalent pneumococcal conjugate
      vaccine (PCV7). Cefotaxime non-susceptibility was high (51.4%) in S. pneumoniae
      nasopharyngeal isolates. Serotype 6B was the most common in fully immunized
      carriers and also in those who received catch-up immunization. Due to low PCV7
      coverage in Taiwan, the carriage of vaccine and non-vaccine serotypes of S.
      pneumoniae in children remains common.

PMID- 21892898
TI  - A review of murine models of latent tuberculosis infection.
AB  - The mechanisms of latency and the causes of reactivation of Mycobacterium
      tuberculosis remain poorly understood; an important reason for this gap in
      knowledge is the absence of a standardized animal model of latent tuberculosis
      infection (LTBI). A complete LTBI model should incorporate 2 aspects of LTBI: a
      persistent infection model with a low bacterial load and a latent infection model
      that is modified from the Cornell model. Many parameters must be carefully
      considered to establish an LTBI model, including the inoculating dose, the route
      of infection, the time interval between infection and the initiation of
      antibiotic therapy, and the genetic background of the host animal. The
      responsiveness of this mouse model of LTBI can be assessed through the integrated
      use of indices, including Karnofsky performance status, bacterial load in spleen
      and lungs, induced levels of interferon-gamma and tumour necrosis factor-alpha,
      expression of interleukin (IL)-10 and IL-4 in tissues, specific antigen load in
      organs, time required for hormone-induced TB relapse, expression level of
      dormancy genes, and CD4 T-cell count.

PMID- 21892899
TI  - Early detection of severe sepsis in the emergency room: diagnostic value of
      plasma C-reactive protein, procalcitonin, and interleukin-6.
AB  - OBJECTIVES: To determine the diagnostic values of plasma C-reactive protein
      (CRP), procalcitonin (PCT), and interleukin-6 (IL-6) using an
      electrochemiluminescence immunoassay (ECLIA) method (Roche Diagnostics GmbH,
      Mannheim, Germany) to identify severe sepsis in an emergency room (ER) setting.
      METHODS: This was a single-centre prospective follow-up study of 539 consecutive
      adult patients admitted to the ER with suspected infection. Blood samples were
      taken concurrently with blood cultures at admission. Patients were divided into 5
      groups on the basis of systemic inflammatory response syndrome (SIRS) criteria,
      documentation of bacterial infection, and organ dysfunction. Fifty-nine patients
      with no SIRS or bacterial infection, 68 patients with bacterial infection but no
      SIRS, 54 patients with SIRS but no bacterial infection, 309 patients with sepsis
      (SIRS and bacterial infection), and 49 patients with severe sepsis (sepsis and
      organ failure) were evaluated. RESULTS: In a logistic regression model, the odds
      ratio (OR) for PCT was 1.58 (95% confidence interval (CI) 1.37-1.82, p < 0.0001),
      for IL-6 was 1.54 (95% CI 1.32-1.80, p < 0.0001), and for CRP was 1.33 (95% CI
      1.01-1.75, p = 0.045). The area under the curve (AUC) was 0.77 (95% CI 0.71-0.84)
      for PCT, 0.72 (95% CI 0.64-0.80) for IL-6, and 0.60 (95% CI 0.51-0.69) for CRP.
      PCT emerged as the best marker for severe sepsis, but the difference in AUC was
      not significant between PCT and IL-6. In multivariate logistic regression
      analysis, after adjusting for confounders, PCT and IL-6 remained significant
      independent predictors of severe sepsis. CONCLUSIONS: PCT and IL-6 proved
      superior to CRP in detecting patients with severe sepsis. The findings thus
      support the use of either PCT or IL-6 as an early tool to diagnose severe sepsis.
      The automatic ECLIA method allows even night-shift measurements.

PMID- 21892900
TI  - Effect of chewing gum on static posturography in patients with balance disorders.
AB  - CONCLUSION: The chewing gum indirectly affects postural control by influencing
      vestibular function to stabilize posture during upright standing. OBJECTIVES:
      This study aimed to evaluate the effect of chewing gum on static posturography in
      patients. METHODS: The subjects were 26 patients with chronic balance disorders.
      The subjects were instructed to stand as stably as possible on the force
      platform. The recording was conducted four times. For the first evaluation,
      postural sway was measured during motionless standing. Two weeks after the
      recording, the postural sway was recorded again as a second evaluation.
      Thereafter, the subjects were instructed to chew gum for 3 min. The third
      evaluation was conducted while the subjects continued to chew gum. Then 1 h after
      the subject had stopped chewing gum, a fourth evaluation was obtained. The total
      path length (LNG) and rectangle area (REC) were analyzed. RESULTS: We found that
      postural stability tended to improve while the subjects masticated gum. Both LNG
      and REC were significantly improved while the subjects chewed gum with their eyes
      closed. In patients without canal paralysis (CP), the measurements of LNG with
      eyes closed and REC with eyes open were significantly decreased while masticating
      gum. In patients with CP, the REC, but not LNG, was significantly decreased while
      masticating gum both with eyes open and eyes closed.

PMID- 21892901
TI  - The reproductive health report: The state of sexual and reproductive health
      within the European Union.

PMID- 21892902
TI  - Natriuretic peptide levels in intrauterine growth-restricted fetuses with absent
      and reversed end-diastolic flow of the umbilical artery in relation to ductus
      venosus flow velocities.
AB  - OBJECTIVE: To determine if changes in natriuretic peptide levels [propeptide of
      atrial natriuretic peptide (proANP) and N-terminal propeptide of brain
      natriuretic peptide (NT-proBNP)] can be demonstrated in fetuses with serious
      growth restriction and Doppler ultrasonographic findings of hemodynamic
      compromise. METHOD: Natriuretic peptides of the umbilical vein (proANP and NT
      proBNP), arterial and venous blood gases, as well as lactate levels of the
      umbilical vein were determined in 38 appropriate for gestational age (AGA)
      fetuses, and 24 intrauterine growth-restricted (IUGR) fetuses with absent (zero
      flow) and 17 IUGR fetuses with reversed end-diastolic flow (reverse-flow) of the
      umbilical artery. RESULTS: A continuous increase in natriuretic peptides in the
      presence of progressive deterioration was shown. ANP concentrations were
      significantly lower in the AGA group (mean 818 fmol/mL; range 508-991 fmol/mL)
      than the zero-flow group (mean 19,680 fmol/mL; range 13,680-25,080 fmol/mL) and
      the reverse-flow group (mean 33,880 fmol/mL; range 24,365-41,786 fmol/mL).
      Significant differences were further demonstrated in BNP concentrations of the
      AGA group (mean 32 fmol/L; range 25-38 fmol/L), zero-flow group (mean 1191
      fmol/L; range 908-1655 fmol/L), and reverse-flow group (mean 3063 fmol/L; range
      1281-4968 fmol/L). Additionally, significant differences in lactate
      concentrations were observed for the three groups: AGA, 2.6 mmol/L (range 2-3
      mmol/L); zero-flow group, 4.1 mmol/L (range 3.3-5 mmol/L); and reverse-flow
      group, 7.7 mmol/L (range 5.9-13.7 mmol/L). Increased ANP levels correlated with
      the arterial base excess and lactate concentrations, as well as with the flow
      velocities in the ductus venosus during atrial contraction (a-wave), and both
      ductus venosus indices (S-a)/D and (S-a)/V(mean). No correlations were
      established for BNP. CONCLUSIONS: As components of a compensatory mechanism,
      natriuretic peptides exert an influence on the cardiovascular function of the
      fetus.

PMID- 21892903
TI  - Inter- and intra-observer variation of fetal volume measurements with three
      dimensional ultrasound in the first trimester of pregnancy.
AB  - OBJECTIVES: To determine the inter- and intra-observer variation of volume
      calculations of human fetuses at a gestational age of 11(+0)-13(+6) weeks by
      three-dimensional ultrasound (3DUS). METHODS: 3DUS datasets were acquired during
      nuchal translucency measurements. The fetal volume (FV) was measured in 65 cases
      by two independent investigators. The Virtual Organ Computer aided AnaLysis
      (VOCALTM) imaging software was used to manually calculate the FV (rotational
      angle 9 degrees ). Inter- and intra-observer variation were assessed by Bland
      Altman plots and intraclass correlation coefficients (ICC). RESULTS: Both inter-
      and intraobserver reproducibility were highly reliable as shown by the Bland
      Altman plots and an ICC of respectively 0.934 and 0.994. CONCLUSION: FV
      calculation by 3DUS with VOCAL and a rotational angle of 9 degrees  is feasible
      and has a high inter- and intraobserver reliability in the first trimester of
      pregnancy.

PMID- 21892906
TI  - Role of biomarkers in cardioncology.
AB  - Cardiotoxicity is a serious adverse effect of anticancer drugs, impacting on
      quality of life and overall survival of cancer patients. According to the current
      standard for monitoring cardiac function, cardiotoxicity is usually detected only
      when a functional impairment has already occurred, precluding any chance of
      preventing its development. Over the last decade, however, a new approach, based
      on the use of cardiac biomarkers, has emerged, and has proven to be an effective
      alternative strategy for early detection of subclinical cardiac injury. In
      particular, the role of troponin I in identifying patients at risk of
      cardiotoxicity and of angiotensin-converting enzyme inhibitors in preventing left
      ventricular ejection fraction reduction and late cardiac events represent an
      effective tool for the prevention of this complication.

PMID- 21892905
TI  - High-sensitive troponin T in chronic heart failure correlates with severity of
      symptoms, left ventricular dysfunction and prognosis independently from N
      terminal pro-b-type natriuretic peptide.
AB  - BACKGROUND: Troponin T is an established marker of myocardial ischemia. We
      speculated that the role of the new high-sensitive troponin T (hs-cTnT) might
      expand towards non-ischemic myocardial disease, indicate disease severity and
      allow for prognostication in chronic heart failure. METHODS: Hs-cTnT (Roche
      Diagnostics, Mannheim, Germany) was assessed in 233 individuals with chronic
      heart failure (n=149) or healthy controls (n=84). RESULTS: Hs-cTnT was
      significantly elevated in patients with chronic heart failure [0.018 ng/mL,
      interquartile range (IQR) 0.009-0.036 ng/mL, vs. controls 0.003 ng/mL, 0.003
      0.003 ng/mL, p<0.001] and positively correlated with N-terminal pro-b-type
      natriuretic peptide (NT-proBNP) (r=0.79, p<0.001). Hs-cTnT increased stepwise and
      signitificantly according to clinical (NYHA stage) as well as functional (LV
      ejection fraction, fluid retention) severity (each p<0.001). At a binary cutpoint
      of 0.014 ng/mL, hs-TropT was a significant predictor of all-cause mortality and
      all-cause mortality or rehospitalization for congestive heart failure (each
      p<=0.01). Of note, the prognostic value of hs-TropT was independent and additive
      to that of NT-proBNP. CONCLUSIONS: Hs-cTnT increases stepwise with the severity
      of symptoms and LV dysfunction and offers important prognostic information in
      chronic heart failure, independently from and additive to NT-proBNP. The utility
      of hs-cTnT expands beyond acute myocardial ischemia and towards chronic heart
      failure.

PMID- 21892907
TI  - High-sensitivity troponin assays in the evaluation of patients with acute chest
      pain in the emergency department.
AB  - Evaluating patients with acute chest pain presenting to the emergency department
      remains an ongoing challenge. The spectrum of etiologies in acute chest pain
      ranges from minor disease entities to life-threatening diseases, such as
      pulmonary embolism, acute aortic dissection or acute myocardial infarction (MI).
      The diagnosis of acute MI is usually made integrating the triad of patient
      history and clinical presentation, readings of 12-lead ECG and measurement of
      cardiac troponins (cTn). Introduction of high-sensitivity cTn assays
      substantially increases sensitivity to identify patients with acute MI even at
      the time of presentation to the emergency department at the cost of specificity.
      However, the proportion of patients presenting with cTn positive, non-vascular
      cardiac chest pain triples with the implementation of new sensitive cTn assays
      increasing the difficulty for the emergency physician to identify those patients
      who are at need for invasive diagnostics. The main objectives of this mini-review
      are 1) to discuss elements of disposition decision made by the emergency
      physician for the evaluation of chest pain patients, 2) to summarize recent
      advances in assay technology and relate these findings into the clinical context,
      and 3) to discuss possible consequences for the clinical work and suggest an
      algorithm for the clinical evaluation of chest pain patients in the emergency
      department.

PMID- 21892908
TI  - Increased plasma concentrations of tumour markers in the absence of neoplasia.
AB  - Tumour markers are a very heterogeneous group of molecules that are generally
      found in very small concentrations in the plasma and serum of healthy
      individuals. In the process of neoplastic differentiation the cell can
      synthesize, release, or induce synthesis of other cells, thus increasing their
      concentration in plasma and serum. These substances may also increase their
      plasma concentration in patients without cancer due to processes that increase
      the release or reduce catabolism, and so give rise to false positives. An
      understanding of the main physiopathological processes that increase the
      concentrations of these substances could improve our interpretation of tumour
      markers and their clinical application. In this study we review the
      physiopathological processes that may increase the plasma concentrations of
      tumour markers. We performed a bibliography review in PubMed, searching for
      causes of false positives for the following tumour markers: alpha-Fetoprotein, CA
      125, CA 15-3, CA 19-9, CA 72-4, carcinoembryonic antigen, CYFRA 21-1, squamous
      cell carcinoma, prostatic specific antigen, beta(2)-microglobulin,
      choriogonadotropin (beta chain), chromogranin A, neuron specific enolase, HER2
      neu, progastrin releasing peptide, S-100, and thyroglobulin. The results favour
      the use of tests which can identify pathological processes that may increase
      tumour marker concentrations.

PMID- 21892909
TI  - Rapid HLA-B27 screening with real-time TaqMan PCR: a clinical validation in the
      Dutch population.
AB  - BACKGROUND: Human leukocyte antigen B27 (HLA-B27) is strongly associated with
      ankylosing spondylitis. The B27 allele is present in 90% of patients with this
      disease, whereas it is present in only 9% of Caucasians. Molecular detection of
      HLA-B27 is traditionally based on allele specific amplification of exon 2 (Olerup
      method) or exon 3 (Dominguez method) by PCR, followed by gel analysis. METHODS:
      We developed a real-time TaqMan PCR based on the Dominguez method with a beta
      Globin PCR as internal control. RESULTS: A total of 544 clinical samples were
      used to compare the real-time TaqMan PCR with the traditional Dominguez PCR, the
      traditional Olerup PCR and a commercial Olerup based HLA-B27 detection kit
      (Olerup SSPTM HLA-B27, GenoVision). While 542 samples gave concordant results,
      two samples showed discrepancies and were further analyzed. One sample that
      showed a discrepancy was negative with the traditional Olerup method and positive
      with the three other procedures. Sequencing analysis showed the presence of HLA
      B*2712 in this sample. The other sample, positive with both Olerup based PCRs and
      negative with both Dominguez based methods, turned out to be positive for HLA
      B*2707 by sequence analysis. CONCLUSIONS: With a correct result for 543 out of
      544 samples (99.8%), we consider our real-time HLA-B27 PCR is a reliable method
      to detect HLA-B27 in the Dutch population, with reduced hands-on time and
      contamination risk compared to traditional PCR methods.

PMID- 21892911
TI  - Thank you, indeed!

PMID- 21892910
TI  - Determination of asymmetric dimethyl arginine in human serum by liquid
      chromatography-tandem mass spectrometry: clinical application in hypertensive
      subjects.
AB  - BACKGROUND: Asymmetric dimethylarginine (ADMA), an endogenous competitive
      inhibitor of nitric oxide synthase plays an important role in endothelial
      dysfunction processes. Recent studies have linked high ADMA levels with several
      pathological conditions. The interest as a marker of endothelial dysfunction has
      increased in the last few years. In this paper, a method for serum ADMA
      quantification by liquid chromatography tandem mass spectrometry has been
      described. To test the utility in a pathological condition ADMA levels in
      hypertensive subjects have been measured. METHODS: HPLC separation was performed
      by hydrophilic interaction chromatography using acetonitrile/water containing
      0.1% formic acid and 20 mmol/L ammonium formate. Selected reaction monitoring was
      performed following the transitions m/z 203.1->46.4 for ADMA and 210.1->46.3 for
      the internal standard [2H7]ADMA. RESULTS: The method was linear up to 10 MUmol/L,
      limit of detection and limit of quantification were 0.005 MUmol/L and 0.01
      MUmol/L, respectively. Recovery was higher than 96%. Intra- and inter-assay
      imprecision were lower than 6%. The accuracy, expressed as bias %, was <2.5. ADMA
      in "healthy" subjects ranged from 0.343 to 0.608 MUmol/L and resulted
      significantly lower than that measured in hypertensive subjects (p<0.001).
      CONCLUSIONS: The method developed is selective and sensitive, thus suitable not
      only for research purposes, but also for routinely work.

PMID- 21892912
TI  - Influence of hemolysis on troponin testing: studies on Beckman Coulter UniCel Dxl
      800 Accu-TnI and overview of the literature.
AB  - BACKGROUND: Hemolyzed specimens are the leading pre-analytical problem in the
      laboratory practice, and exert a negative impact on test results. We assessed the
      reliability of Beckman Coulter UniCel Dxl 800 Accu-TnI testing on hemolyzed
      specimens. METHODS: Twelve non-hemolyzed K2EDTA-anticoagulated samples displaying
      Accu-TnI values >0.20 MUg/L and nine with values <0.04 MUg/L were selected and
      three aliquots were obtained from each. The first ("#A") was processed without
      further manipulation, whereas the second ("#B") and third ("#C") were hemolyzed
      by aspirating anticoagulated blood through a thin needle. Plasma was separated
      and tested for hemolysis index (HI) and Accu-TnI. RESULTS: As compared with
      aliquot #A (HI: 0), a progressive increase of hemolysis occurred in aliquots #B
      (HI: 25) and #C (HI: 45). The concentration of Accu-TnI gradually decreased from
      aliquots #A (0.89 MUg/L, 0.20-20.16 MUg/L), to aliquots #B (0.81 MUg/L, 95% CI
      0.17-18.37 MUg/L; p=0.041) and #C (0.78 MUg/L, 95% CI 0.15-17.48 MUg/L; p=0.026).
      In 0/12 (aliquots #B) and 3/12 cases (aliquots #C) the percent decrease exceeded
      20% variation. The values remained unchanged in nine samples with Accu-TnI <0.04
      MUg/L. CONCLUSIONS: Accu-TnI values decrease in hemolyzed samples, but the bias
      might not be clinically significant in samples with hemoglobin <14.5 g/L.

PMID- 21892913
TI  - New insights into adipose tissue dysfunction in insulin resistance.
AB  - In a state of caloric excess, adipose tissue plays an essential role by storing
      lipids. Its expandability determines the onset of metabolic syndrome (central
      obesity, dyslipidemia, glucose intolerance and hypertension). When the adipocyte
      endoplasmic reticulum is no longer capable of processing the excess nutrients,
      the so-called "endoplasmic reticulum stress" develops. This triggers efflux of
      free fatty acids from adipocytes into the circulation and causes triglyceride
      overload in skeletal muscle, liver and pancreas. Adipose tissue hypoxia then
      develops, due to the failure of vasculature to expand with adipocyte hypertrophy.
      Increased catabolism in mitochondria leads there to oxidative stress. Both
      phenomena cause deranged adipokine secretion and low-grade inflammation.
      Inflammatory cytokines, reactive oxygen species and ectopic lipid deposition are
      the main mediators of insulin resistance and vascular impairment, which both lead
      finally to diabetes type 2 and cardiovascular disease. Recently, fibrosis of
      adipose tissue was also demonstrated in obesity, contributing to the interplay of
      deleterious factors forcing inflammation. The present paper reviews recent
      evidence for adipose tissue dysfunction, trying to define causes and
      consequences. In conclusion, insulin resistance and associated complications
      originate from excess lipids, which cannot be stored without limit in adipose
      tissue, thus affecting its integrity and adipokine secretion.

PMID- 21892914
TI  - beta-Thalassemia mutations in subjects with borderline HbA2 values: a pilot study
      in North India.
AB  - BACKGROUND: Interpreting hemoglobin high performance liquid chromatograms with
      borderline HbA2 values is often problematic, especially in antenatal cases if the
      partner is a known thalassemia trait. METHODS: We tested for underlying beta
      thalassemia mutations in 25 subjects with borderline HbA2 values (between 3.0%
      4.0%). Amplification refractory mutation system (ARMS-PCR) was used to detect the
      five common Indian beta-thalassemia mutations: (IVS-I-5 (G>C), IVS-I-1 (G>T),
      codons 8/9 (+G), codons 41/42 (-TTCT) and 619 bp deletion). beta-Globin gene
      sequencing was performed if no mutation was detected. RESULTS: A beta-globin gene
      defect was identified in 8 (32%) of the 25 cases with HbA2 levels ranging from
      3.5%-3.9%. ARMS-PCR revealed IVS-I-5 (G>C) in three, 619 bp deletion in two and
      codons 41/42 (-TTCT) in one case. Two cases had CAP +1 (A>C) mutation on gene
      sequencing. IVS-I-1 (G>T) and codons 8/9 (+G) were not found in this small
      cohort. CONCLUSIONS: Mutation analysis should be offered to all at-risk couples
      with borderline HbA2, especially those with values between 3.5% and 4.0% and
      microcytic hypochromic indices. Significant mutations different from those in
      other ethnic populations were seen in this small institution-based study.

PMID- 21892915
TI  - MicroRNA-21 inhibits toll-like receptor 2 agonist-induced lung inflammation in
      mice.
AB  - Impaired airway innate immunity (e.g., suppressed Toll-like receptor 2 [TLR2]
      signaling) has been reported in allergic lungs with bacterial infection.
      Recently, an allergic mouse lung milieu including the T-helper type 2 (Th2)
      cytokine interleukin-13 (IL-13) has been shown to up-regulate lung microRNA-21
      (miR-21) expression. Whether miR-21 modulates in vivo TLR2 signaling is unknown.
      The goal of this study was to determine if in vivo, miR-21 regulates a TLR2
      agonist-induced lung inflammatory response. Balb/c mice were intranasally
      pretreated with a locked nucleic acid (LNA) in vivo inhibitor probe for mouse miR
      21 or a control probe, followed by intranasal instillation of a TLR2 agonist
      Pam3CSK4, or saline (control). Four and/or 24 hours later, mice treated with the
      miR-21 inhibitor probe, as compared to the control probe, significantly increased
      lung leukocytes, including neutrophils and the keratinocyte-derived chemokine
      (KC). IL-13 treatment for 72 hours increased (P < .05) miR-21 in cultured primary
      normal human airway epithelial cells. These results, for the first time, suggest
      an in vivo role of miR-21 in suppressing TLR2 signaling, and further support that
      IL-13 can up-regulate miR-21 in human airway epithelial cells. Functional studies
      on miR-21 likely provide novel approaches to modulate TLR2 signaling in Th2
      cytokine-exposed airways.

PMID- 21892916
TI  - Toxicities by herbal medicines with emphasis to traditional Chinese medicine.
AB  - It is estimated that three quarters of the world population rely on herbal and
      traditional medicine as a basis for primary health care. Therefore, it is one of
      the most important and challenging tasks for scientists working in drug research
      to investigate the efficacy of herbal medicine, to dissect favorable from adverse
      effects, to identify active principles in medicinal plants and to ban poisonous
      plants or contaminations from herbal mixtures. In the present review, some
      problems are critically discussed. Botanical misidentification or mislabeling of
      plant material can play a role for toxic reactions in humans. Some plant
      descriptions in traditional herbal medicine (e.g. traditional Chinese medicine)
      have changed over time, which may lead to unintended intoxication by using wrong
      plants. A problem is also the contamination of herbals with microorganisms,
      fungal toxins such as aflatoxin, with pesticides and heavy metals. Unprofessional
      processing, which differs from safe traditional preparation represents another
      potential source for herbal poisoning. Unwanted effects of herbal products may
      also develop by the interaction of herbs with conventional drugs upon concomitant
      intake. The art of herbal medicine is to dissect pharmacologically and
      therapeutically valuable herbal drugs from harmful and toxic ones and to develop
      combinations of medicinal plants as safe and efficient herbal remedies.
      Standardization and strict control measures are necessary to monitor sustainable
      high quality of herbal products and to exclude contaminations that badly affect
      patients consuming herbal medicine.

PMID- 21892917
TI  - PEGylation of proteins and liposomes: a powerful and flexible strategy to improve
      the drug delivery.
AB  - PEGylation is one of the most successful strategies to improve the delivery of
      therapeutic molecules such as proteins, macromolecular carriers, small drugs,
      oligonucleotides, and other biomolecules. PEGylation increase the size and
      molecular weight of conjugated biomolecules and improves their pharmacokinetics
      and pharmacodinamics by increasing water solubility, protecting from enzymatic
      degradation, reducing renal clearance and limiting immunogenic and antigenic
      reactions. PEGylated molecules show increased half-life, decreased plasma
      clearance, and different biodistribution, in comparison with non-PEGylated
      counterparts. These features appear to be very useful for therapeutic proteins,
      since the high stability and very low immunogenicity of PEGylated proteins result
      in sustained clinical response with minimal dose and less frequent
      administration. PEGylation of liposomes improves not only the stability and
      circulation time, but also the 'passive' targeting ability on tumoral tissues,
      through a process known as the enhanced permeation retention effect, able to
      improve the therapeutic effects and reduce the toxicity of encapsulated drug. The
      molecular weight, shape, reactivity, specificity, and type of bond of PEG moiety
      are crucial in determining the effect on PEGylated molecules and, at present,
      researchers have the chance to select among tens of PEG derivatives and PEG
      conjugation technologies, in order to design the best PEGylation strategy for
      each particular application. The aim of the present review will be to elucidate
      the principles of PEGylation chemistry and to describe the already marketed
      PEGylated proteins and liposomes by focusing our attention to some enlightening
      examples of how this technology could dramatically influence the clinical
      application of therapeutic biomolecules.

PMID- 21892918
TI  - The ligand nanoparticle conjugation approach for targeted cancer therapy.
AB  - Cancer therapy often requires frequent and high drug dosing. Yet, despite the
      significant progress in cancer research and the wide versatility of potent
      available drugs, treatment efficacy is still hurdled and often failed by the lack
      of pharmaco-selectivity to diseased cells, indiscriminate drug toxicities and
      poor patient compliance. Thus, innovative pharmaceutical solutions are needed to
      effectively deliver the cytotoxic drugs specifically to the tumor site while
      minimizing systemic exposure to frequent and high drug doses. Polymeric
      nanocarriers, particularly nanoparticles, have been extensively studied for
      improved oncological use. Such nanocarriers hold great potential in cancer
      treatment as they can be biocompatible, adapted to specific needs, tolerated and
      deliver high drug payloads while targeting tumors. Active targeting, as opposed
      to passive targeting, should add value to selective and site specific treatment.
      Active targeting of nanosized drug delivery systems is firmly rooted in the Magic
      Bullet Concept as was envisioned by Paul Ehrlich over 100 years ago. This
      targeting strategy is based on the molecular recognition of tumor biomarkers
      which are over-expressed on cancer cells, via specific vector molecules
      conjugated to the surface of the drug carrier. These vector molecules dictate the
      carrier's biodistribution and its biological affinity to the desired site of
      action. Many recent publications have shown encouraging results suggesting that
      targeting nanocarriers represent a highly-promising strategy for improved cancer
      treatment. This chapter will focus mainly on polymeric nanoparticles as the main
      drug carriers to be conjugated to various ligands able to deliver the drug to the
      specific desired pathological tissue.

PMID- 21892920
TI  - Hsp70 in oncology.
AB  - Hsp70 classes of molecular chaperones are highly conserved in all organisms and
      play an essential role in the maintenance of cellular homeostasis. Hsp70s assist
      nascent chain protein folding and denatured proteins, as well as the import of
      proteins to the organelles, and solubilization of aggregated proteins. ATPase
      function is required for Hsp70 function. Hsp70s use ATP hydrolysis driven
      mechanism for substrate protein binding and release. Various Hsps are unregulated
      in cancers but their significance for tumor growth is poorly understood. Studies
      have linked Hsp70 to several types of carcinoma. Human Hsp70s allow proliferation
      of cancer cells and suppress apoptotic and senescence pathways. This review
      presents Hsp70s role for growth of transformed cells and the current state of
      Hsp70 as a drug target along with recent patents in humans in this particular
      area.

PMID- 21892919
TI  - Design of curcumin loaded cellulose nanoparticles for prostate cancer.
AB  - Prostate cancer (PC) is the most frequently diagnosed disease in men in the
      United States. Curcumin (CUR), a natural diphenol, has shown potent anti-cancer
      efficacy in various types of cancers. However, suboptimal pharmacokinetics and
      poor bioavailability limit its effective use in cancer therapeutics. Several
      successful CUR nanoformulations have recently been reported which improve upon
      these features; however, there is no personalized safe nanoformulation for
      prostate cancer. This study contributes two important scientific aspects of
      prostate cancer therapeutics. The first objective was to investigate the
      comparative cellular uptake and cytotoxicity evaluation of beta-cyclodextrin
      (CD), hydroxypropyl methylcellulose (cellulose), poly(lactic-co-glycolic acid)
      (PLGA), magnetic nanoparticles (MNP), and dendrimer based CUR nanoformulations in
      prostate cancer cells. Curcumin loaded cellulose nanoparticles (cellulose-CUR)
      formulation exhibited the highest cellular uptake and caused maximum
      ultrastructural changes related to apoptosis (presence of vacuoles) in prostate
      cancer cells. Secondly, the anti-cancer potential of the cellulose-CUR
      formulation was evaluated in cell culture models using cell proliferation, colony
      formation and apoptosis (7-AAD staining) assays. In these assays, the cellulose
      CUR formulation showed improved anti-cancer efficacy compared to free curcumin.
      Our study shows, for the first time, the feasibility of cellulose-CUR formulation
      and its potential use in prostate cancer therapy.

PMID- 21892921
TI  - PKCbeta inhibition with ruboxistaurin reduces oxidative stress and attenuates
      left ventricular hypertrophy and dysfunction in rats with streptozotocin-induced
      diabetes.
AB  - Oxidative stress plays critical roles in the development of diabetic
      cardiovascular complications, including myocardial hypertrophy. The beta isoform
      of PKC (protein kinase C) is preferentially overexpressed in the myocardium of
      diabetic subjects accompanied with increased activation of the pro-oxidant enzyme
      NADPH oxidase, which may exacerbate oxidative stress. We hypothesized that
      myocardial PKCbeta is a major upstream mediator of oxidative stress in diabetes
      and that PKCbeta inhibition can attenuate myocardial hypertrophy and dysfunction.
      Control or streptozotocin-induced diabetic rats were treated with the selective
      PKCbeta inhibitor RBX (ruboxistaurin; 1 mg/kg of body weight per day) or the
      antioxidant NAC (N-acetylcysteine) for 4 weeks. LV (left ventricular) dimensions
      and functions were detected by echocardiography. 15-F2t-isoprostane (a specific
      index of oxidative stress) and myocardial activities of superoxide dismutase as
      well as protein levels of NADPH oxidase were assessed by immunoassay or Western
      blotting. Echocardiography revealed that the LV mass/body weight ratio was
      significantly increased in diabetic rats (P<0.01 compared with the control group)
      in parallel with the impaired LV relaxation. A significant increase in
      cardiomyocyte cross-sectional area was observed in diabetic rats accompanied by
      an increased production of O2- (superoxide anion) and 15-F2t-isoprostane (all
      P<0.05 compared with the control group). RBX normalized these changes with
      concomitant inhibition of PKCbeta2 activation and prevention of NADPH oxidase
      subunit p67phox membrane translocation and p22phox overexpression. The effects of
      RBX were comparable with that of NAC, except that NAC was inferior to RBX in
      attenuating cardiac dysfunction. It is concluded that RBX can ameliorate
      myocardial hypertrophy and dysfunction in diabetes, which may represent a novel
      therapy in the prevention of diabetic cardiovascular complications.

PMID- 21892923
TI  - Neurotrophin-4 modulates the mechanotransducer Cav3.2 T-type calcium current in
      mice down-hair neurons.
AB  - The T-type Ca2+ channel Cav3.2 is expressed in nociceptive and mechanosensitive
      sensory neurons. The mechanosensitive D-hair (down-hair) neurons, which innervate
      hair follicles, are characterized by a large-amplitude Cav3.2 T-current involved
      in the amplification of slow-moving stimuli. The molecules and signalling
      pathways that regulate T-current expression in mechanoreceptors are unknown. In
      the present study, we investigated the effects of NT-4 (neurotrophin-4) on Cav3.2
      T-current expression in D-hair neurons in vitro. Interruption of the supply of NT
      4 with peripheral nerve axotomy induced a non-transcriptional decrease in the T
      current amplitude of fluorogold-labelled axotomized sensory neurons. The T
      current amplitude was restored by incubation with NT-4. Deletion of NT-4 through
      genetic ablation resulted in a similar selective loss of the large-amplitude T
      current in NT-4-/- sensory neurons, which was rescued by the addition of NT-4. NT
      4 had no effect on the T-current in Cav3.2-/- D-hair neurons. Neither the
      biophysical properties of the T-current nor the transcript expression of Cav3.2
      were modified by NT-4. Pharmacological screening of signalling pathways activated
      under the high-affinity NT-4 receptor TrkB (tropomyosin receptor kinase B)
      identified a role for PI3K (phosphoinositide 3-kinase) in the potentiation of T
      current. The results of the present study demonstrate the post-transcriptional up
      regulation of the Cav3.2 T-current through TrkB activation and identify NT-4 as a
      target-derived factor that regulates the mechanosensitive function of D-hair
      neurons through expression of the T-current.

PMID- 21892922
TI  - Selenium-containing amino acids are targets for myeloperoxidase-derived
      hypothiocyanous acid: determination of absolute rate constants and implications
      for biological damage.
AB  - Elevated MPO (myeloperoxidase) levels are associated with multiple human
      inflammatory pathologies. MPO catalyses the oxidation of Cl-, Br- and SCN- by
      H2O2 to generate the powerful oxidants hypochlorous acid (HOCl), hypobromous acid
      (HOBr) and hypothiocyanous acid (HOSCN) respectively. These species are
      antibacterial agents, but misplaced or excessive production is implicated in
      tissue damage at sites of inflammation. Unlike HOCl and HOBr, which react with
      multiple targets, HOSCN targets cysteine residues with considerable selectivity.
      In the light of this reactivity, we hypothesized that Sec (selenocysteine)
      residues should also be rapidly oxidized by HOSCN, as selenium atoms are better
      nucleophiles than sulfur. Such oxidation might inactivate critical Sec-containing
      cellular protective enzymes such as GPx (glutathione peroxidase) and TrxR
      (thioredoxin reductase). Stopped-flow kinetic studies indicate that seleno
      compounds react rapidly with HOSCN with rate constants, k, in the range 2.8*10(3)
      5.8*10(6) M-1.s-1 (for selenomethionine and selenocystamine respectively). These
      values are ~6000-fold higher than the corresponding values for H2O2, and are also
      considerably larger than for the reaction of HOSCN with thiols (16-fold for
      cysteine and 80-fold for selenocystamine). Enzyme studies indicate that GPx and
      TrxR, but not glutathione reductase, are inactivated by HOSCN in a concentration
      dependent manner; k for GPx has been determined as ~5*105 M-1.s-1. Decomposed
      HOSCN did not induce inactivation. These data indicate that selenocysteine
      residues are oxidized rapidly by HOSCN, with this resulting in the inhibition of
      the critical intracellular Sec-dependent protective enzymes GPx and TrxR.

PMID- 21892924
TI  - Inhibition of polyglutamine-mediated proteotoxicity by Astragalus membranaceus
      polysaccharide through the DAF-16/FOXO transcription factor in Caenorhabditis
      elegans.
AB  - Late-onset neurodegenerative diseases are characterized by progressive
      accumulation of aggregation-prone proteins and global disruption of the
      proteostasis network, e.g. abnormal polyQ (polyglutamine) aggregation in
      Huntington's disease. Astragalus membranaceus polysaccharide (astragalan) has
      recently been shown to modulate aging and proteotoxic stress pathways. Using
      Caenorhabditis elegans models, we now show that astragalan not only reduces polyQ
      aggregation, but also alleviates the associated neurotoxicity. We also reveal
      that astragalan can extend the adult lifespan of wild-type and polyQ nematodes,
      indicating a connection of its anti-aging benefit with the toxicity-suppressing
      effect. Further examination demonstrates that astragalan can extend the lifespan
      of daf-2 and age-1, but not daf-16, mutant nematodes of the insulin-like aging
      and stress pathway, suggesting a lifespan-regulation signalling independent of
      DAF (abnormal dauer formation)-2/IGF-1R (insulin-like growth factor 1 receptor),
      but dependent on the DAF-16/FOXO (forkhead box O) transcription factor, a pivotal
      integrator of divergent signalling pathways related to both lifespan regulation
      and stress resistance. We also show that a subset of DAF-16 downstream genes are
      regulated by astragalan, including the DAF-16 transcriptional target gene scl-20,
      which is itself constitutively up-regulated in transgenic polyQ nematodes. These
      findings, together with our previous work on LEA (late embryogenesis abundant)
      proteins and trehalose, provide a revealing insight into the potential of stress
      and lifespan regulators in the prevention of proteotoxic disorders.

PMID- 21892925
TI  - Folklore and traditional ecological knowledge of geckos in Southern Portugal:
      implications for conservation and science.
AB  - Traditional Ecological Knowledge (TEK) and folklore are repositories of large
      amounts of information about the natural world. Ideas, perceptions and empirical
      data held by human communities regarding local species are important sources
      which enable new scientific discoveries to be made, as well as offering the
      potential to solve a number of conservation problems. We documented the gecko
      related folklore and TEK of the people of southern Portugal, with the particular
      aim of understanding the main ideas relating to gecko biology and ecology. Our
      results suggest that local knowledge of gecko ecology and biology is both
      accurate and relevant. As a result of information provided by local inhabitants,
      knowledge of the current geographic distribution of Hemidactylus turcicus was
      expanded, with its presence reported in nine new locations. It was also
      discovered that locals still have some misconceptions of geckos as poisonous and
      carriers of dermatological diseases. The presence of these ideas has led the
      population to a fear of and aversion to geckos, resulting in direct persecution
      being one of the major conservation problems facing these animals. It is
      essential, from both a scientific and conservationist perspective, to understand
      the knowledge and perceptions that people have towards the animals, since, only
      then, may hitherto unrecognized pertinent information and conservation problems
      be detected and resolved.

PMID- 21892926
TI  - Decoding of grasping information from neural signals recorded using peripheral
      intrafascicular interfaces.
AB  - BACKGROUND: The restoration of complex hand functions by creating a novel
      bidirectional link between the nervous system and a dexterous hand prosthesis is
      currently pursued by several research groups. This connection must be fast,
      intuitive, with a high success rate and quite natural to allow an effective
      bidirectional flow of information between the user's nervous system and the smart
      artificial device. This goal can be achieved with several approaches and among
      them, the use of implantable interfaces connected with the peripheral nervous
      system, namely intrafascicular electrodes, is considered particularly
      interesting. METHODS: Thin-film longitudinal intra-fascicular electrodes were
      implanted in the median and ulnar nerves of an amputee's stump during a four-week
      trial. The possibility of decoding motor commands suitable to control a dexterous
      hand prosthesis was investigated for the first time in this research field by
      implementing a spike sorting and classification algorithm. RESULTS: The results
      showed that motor information (e.g., grip types and single finger movements)
      could be extracted with classification accuracy around 85% (for three classes
      plus rest) and that the user could improve his ability to govern motor commands
      over time as shown by the improved discrimination ability of our classification
      algorithm. CONCLUSIONS: These results open up new and promising possibilities for
      the development of a neuro-controlled hand prosthesis.

PMID- 21892927
TI  - Cardiac tamponade and paroxysmal third-degree atrioventricular block revealing a
      primary cardiac non-Hodgkin large B-cell lymphoma of the right ventricle: a case
      report.
AB  - INTRODUCTION: Primary cardiac lymphoma is rare. CASE PRESENTATION: We report the
      case of a 64-year-old non-immunodeficient Caucasian man, with cardiac tamponade
      and paroxysmal third-degree atrioventricular block. Echocardiography revealed the
      presence of a large pericardial effusion with signs of tamponade and a right
      ventricular mass was suspected. Scanner investigations clarified the sites,
      extension and anatomic details of myocardial and pericardial infiltration.
      Surgical resection was performed due to the rapid impairment of his cardiac
      function. Analysis of the pericardial fluid and histology confirmed the diagnosis
      of non-Hodgkin large B-cell lymphoma. He was treated with chemotherapy.
      CONCLUSION: The prognosis remains poor for this type of tumor due to delays in
      diagnosis and the importance of the site of disease.

PMID- 21892928
TI  - Laparoscopic resection of a lymphangiomatous cyst of the colon: a case report.
AB  - INTRODUCTION: Lymphangiomatous cysts are submucosal masses that are rarely found
      in the gastrointestinal tract and more often in the neck, oral cavity, and skin.
      These cysts are benign tumors and mostly clinically silent. Symptoms include
      abdominal pain, diarrhea, and rectal bleeding. Their pathogenesis remains
      unclear. CASE PRESENTATION: During a routine ultrasound examination of a
      Caucasian 25-year-old woman, a structure that raised our suspicions of an ovarian
      cyst was found. MRI showed a 4.5 cm cystic lesion in the cecal region.
      Laparoscopic exploration revealed unexpected contact with the ascending colon.
      The cyst, including its base and of portion of the colon, was resected
      laparoscopically. The histological examination revealed cystic lymphangioma.
      CONCLUSION: Lymphangiomatous cysts of the colon are very rare lesions. Although
      their pathology is benign, the recommended treatment is resection, which can be
      performed with minimal invasiveness.

PMID- 21892929
TI  - A three-dimensional model of error and safety in surgical health care
      microsystems. Rationale, development and initial testing.
AB  - BACKGROUND: Research estimates of inadvertent harm to patients undergoing modern
      healthcare demonstrate a serious problem. Much attention has been paid to
      analysis of the causes of error and harm, but researchers have typically focussed
      either on human interaction and communication or on systems design, without fully
      considering the other components. Existing models for analysing harm are
      principally derived from theory and the analysis of individual incidents, and
      their practical value is often limited by the assumption that identifying causal
      factors automatically suggests solutions. We suggest that new models based on
      observation are required to help analyse healthcare safety problems and evaluate
      proposed solutions. We propose such a model which is directed at "microsystem"
      level (Ward and operating theatre), and which frames problems and solutions
      within three dimensions. METHODS: We have developed a new, simple, model of
      safety in healthcare systems, based on analysis of real problems seen in surgical
      systems, in which influences on risk at the "microsystem" level are described in
      terms of only 3 dimensions--technology, system and culture. We used definitions
      of these terms which are similar or identical to those used elsewhere in the
      safety literature, and utilised a set of formal empirical and deductive processes
      to derive the model. The "3D" model assumes that new risks arise in an
      unpredictable stochastic manner, and that the three defined dimensions are
      interactive, in an unconstrained fashion. We illustrated testing of the model,
      using analysis of a small number of incidents in a surgical environment for which
      we had detailed prospective observational data. RESULTS: The model appeared to
      provide useful explanation and categorisation of real events. We made predictions
      based on the model, which are experimentally verifiable, and propose further work
      to test and refine it. CONCLUSION: We suggest that, if calibrated by application
      to a large incident dataset, the 3D model could form the basis for a quantitative
      statistical method for estimating risk at microsystem levels in many acute
      healthcare settings.

PMID- 21892930
TI  - Etiological profile and treatment outcome of epistaxis at a tertiary care
      hospital in Northwestern Tanzania: a prospective review of 104 cases.
AB  - BACKGROUND: Epistaxis is the commonest otolaryngological emergency affecting up
      to 60% of the population in their lifetime, with 6% requiring medical attention.
      There is paucity of published data regarding the management of epistaxis in
      Tanzania, especially the study area. This study was conducted to describe the
      etiological profile and treatment outcome of epistaxis at Bugando Medical Centre,
      a tertiary care hospital in Northwestern Tanzania. METHODS: This was a
      prospective descriptive study of the cases of epistaxis managed at Bugando
      Medical Centre from January 2008 to December 2010. Data collected were analyzed
      using SPSS computer software version 15. RESULTS: A total of 104 patients with
      epistaxis were studied. Males were affected twice more than the females (2.7:1).
      Their mean age was 32.24 +/- 12.54 years (range 4 to 82 years). The modal age
      group was 31-40 years. The commonest cause of epistaxis was trauma (30.8%)
      followed by idiopathic (26.9%) and hypertension (17.3%). Anterior nasal bleeding
      was noted in majority of the patients (88.7%). Non surgical measures such as
      observation alone (40.4%) and anterior nasal packing (38.5%) were the main
      intervention methods in 98.1% of cases. Surgical measures mainly intranasal tumor
      resection was carried out in 1.9% of cases. Arterial ligation and endovascular
      embolization were not performed. Complication rate was 3.8%. The overall mean of
      hospital stay was 7.2 +/- 1.6 days (range 1 to 24 days). Five patients died
      giving a mortality rate of 4.8%. CONCLUSION: Trauma resulting from road traffic
      crush (RTC) remains the most common etiological factor for epistaxis in our
      setting. Most cases were successfully managed with conservative (non-surgical)
      treatment alone and surgical intervention with its potential complications may
      not be necessary in most cases and should be the last resort. Reducing the
      incidence of trauma from RTC will reduce the incidence of emergency epistaxis in
      our centre.

PMID- 21892931
TI  - Antibiotic prescribing pattern in paediatric in patients with first time
      wheezing.
AB  - BACKGROUND: Acute wheezers for the first time in life are an important target
      group for efforts aimed at reducing unnecessary antibiotic use. OBJECTIVE: To
      evaluate the effect of clinical, laboratory and radiological data on the decision
      to prescribe antibiotics to paediatric patients with first time wheezing as well
      as to seek criteria that would justify antibiotic use. METHODS: A prospective
      study was made of 47 previous healthy children admitted to our hospital with
      first time wheezing in life between October 2008- March 2009. All the patients
      were treated as per the treating unit's protocol with oxygen, bronchodilators
      with or without antibiotics. The cases were analyzed after discharge and the
      characteristics of those treated with antibiotics (n = 23) were compared with
      those who were not (n = 24) and analyzed statistically to find the predictors for
      antibiotic usage. RESULTS: The mean age of the study groups was 5.8 (+/- 5.1)
      months. Among the clinical and investigational parameters, presence of
      predominant crackles and abnormalities on radiograph were the major determinants
      for antibiotic usage. There were no significant differences in final outcome
      between these groups. CONCLUSION: Antibiotic usage in first time wheezers is
      still quite prevalent. Presence of crackles and radiological abnormalities often
      prompt the usage of antibiotics in such cases.

PMID- 21892932
TI  - Why are heart operations postponed?
AB  - AIM: To investigate the reasons that lead to postponement of cardiac operations,
      in order to elucidate the problem and help patients through modes of prevention.
      METHODS-DESIGN: We retrospectively included in the study all patients submitted
      to elective adult heart surgery in our department during the 4-year period 2007
      2010 and noted all cases of postponement after official inclusion in the
      operating schedule. RESULTS: 94 out of a total of 575 patients (16.34%) scheduled
      for elective cardiac operation had their procedure postponed. The reasons were
      mainly organisatory (in 49 cases, 52.12%), which in order of significance were:
      unavailability in operating rooms, shortage in matching erythrocyte units and
      shortage in anaesthetic/nursing staff. The rest of the cases (45, 47.88%) were
      postponed due to medical reasons, which in order of significance were: febrile
      situations, including infections of the respiratory, gastrointestinal and urinary
      system, problems with the regulation of antiplatelet and antithrombotic drugs,
      neurological manifestations such as stroke and transient ischaemic attacks,
      exacerbation of asthma/chronic obstructive pulmonary disease, arrhythmias, renal
      problems and allergic reactions to drugs. Patients with advanced age and
      increased Euroscore values were most possible to have their heart operation
      postponed. CONCLUSIONS: Heart operations are postponed due to organisatory as
      well as medical reasons, the latter mainly affecting older, morbid patients who
      therefore require advanced preoperative care.

PMID- 21892933
TI  - Fermented wheat germ extract--nutritional supplement or anticancer drug?
AB  - BACKGROUND: Fermented wheat germ extract (FWGE) is a multisubstance composition
      and, besides others, contains 2-methoxy benzoquinone and 2, 6-dimethoxy
      benzoquinone which are likely to exert some of its biological effects. FWGE
      interferes with anaerobic glycolysis, pentose cycle and ribonucleotide reductase.
      It has significant antiproliferative effects and kills tumor cells by the
      induction of apoptosis via the caspase-poly [ADP-ribose] polymerase-pathway. FWGE
      interacts synergistically with a variety of different anticancer drugs and
      exerted antimetastatic properties in mouse models. In addition, FWGE modulates
      immune response by downregulation of MHC-I complex and the induction of TNF-alpha
      and various interleukins. Data in the F-344 rat model provide evidence for a
      colon cancer preventing effect of FWGE.Clinical data from a randomized phase II
      trial in melanoma patients indicate a significant benefit for patients treated
      with dacarbazine in combination with FWGE in terms of progression free survival
      (PFS) and overall survival (OS). Similarly, data from studies in colorectal
      cancer suggested a benefit of FWGE treatment. Besides extension of OS and PFS,
      FWGE improved the quality of life in several studies. CONCLUSION: In conclusion,
      available data so far, justify the use of FWGE as a non-prescription medical
      nutriment for cancer patients. Further randomized, controlled and large scale
      clinical studies are mandatory, to further clarify the value of FWGE as a drug
      component of future chemotherapy regimens.

PMID- 21892934
TI  - Impact of perioperative RSV or influenza infection on length of stay and risk of
      unplanned ICU admission in children: a case-control study.
AB  - BACKGROUND: Children with viral respiratory infections who undergo general
      anesthesia are at increased risk of respiratory complications. We investigated
      the impact of RSV and influenza infection on perioperative outcomes in children
      undergoing general anesthesia. METHODS: We performed a retrospective case-control
      study. All patients under the age of 18 years who underwent general anesthesia at
      our institution with confirmed RSV or influenza infection diagnosed within 24
      hours following induction between October 2002 and September 2008 were
      identified. Controls were randomly selected and were matched by surgical
      procedure, age, and time of year in a ratio of three controls per case. The
      primary outcome was postoperative length of stay (LOS). RESULTS: Twenty-four
      patients with laboratory-confirmed RSV or influenza who underwent general
      anesthesia prior to diagnosis of viral infection were identified and matched to
      72 controls. Thirteen cases had RSV and 11 had influenza. The median
      postoperative LOS was three days (intra-quartile range 1 to 8 days) for cases and
      two days (intra-quartile range 1 to 5 days) for controls. Patients with influenza
      had a longer postoperative LOS (p < 0.001) and patients with RSV or influenza
      were at increased risk of unplanned admission to the PICU (p = 0.04) than matched
      controls. CONCLUSIONS: Our results suggest that children with evidence of
      influenza infection undergoing general anesthesia, even in the absence of
      symptoms previously thought to be associated with a high risk of complications,
      may have a longer postoperative hospital LOS when compared to matched controls.
      RSV and influenza infection was associated with an increased risk of unplanned
      PICU admission.

PMID- 21892935
TI  - Putative cis-regulatory elements in genes highly expressed in rice sperm cells.
AB  - BACKGROUND: The male germ line in flowering plants is initiated within developing
      pollen grains via asymmetric division. The smaller cell then becomes totally
      encased within a much larger vegetative cell, forming a unique "cell within a
      cell structure". The generative cell subsequently divides to give rise to two non
      motile diminutive sperm cells, which take part in double fertilization and lead
      to the seed set. Sperm cells are difficult to investigate because of their
      presence within the confines of the larger vegetative cell. However, recently
      developed techniques for the isolation of rice sperm cells and the fully
      annotated rice genome sequence have allowed for the characterization of the
      transcriptional repertoire of sperm cells. Microarray gene expression data has
      identified a subset of rice genes that show unique or highly preferential
      expression in sperm cells. This information has led to the identification of cis
      regulatory elements (CREs), which are conserved in sperm-expressed genes and are
      putatively associated with the control of cell-specific expression. FINDINGS: We
      aimed to identify the CREs associated with rice sperm cell-specific gene
      expression data using in silico prediction tools. We analyzed 1-kb upstream
      regions of the top 40 sperm cell co-expressed genes for over-represented
      conserved and novel motifs. Analysis of upstream regions with the SIGNALSCAN
      program with the PLACE database, MEME and the Mclip tool helped to find
      combinatorial sets of known transcriptional factor-binding sites along with two
      novel motifs putatively associated with the co-expression of sperm cell-specific
      genes. CONCLUSIONS: Our data shows the occurrence of novel motifs, which are
      putative CREs and are likely targets of transcriptional factors regulating sperm
      cell gene expression. These motifs can be used to design the experimental
      verification of regulatory elements and the identification of transcriptional
      factors that regulate sperm cell-specific gene expression.

PMID- 21892936
TI  - An evaluation of factors associated with taking and responding positive to the
      tuberculin skin test in individuals with HIV/AIDS.
AB  - BACKGROUND: The tuberculin skin test (TST) is still the standard test for
      detecting latent infection by M tuberculosis (LTBI). Given that the Brazilian
      Health Ministry recommends that the treatment of latent tuberculosis (LTBI)
      should be guided by the TST results, the present study sets out to describe the
      coverage of administering the TST in people living with HIV at two referral
      health centers in the city of Recife, where TST is offered to all patients. In
      addition, factors associated with the non-application of the test and with
      positive TST results were also analyzed. METHODS: A cross-sectional study was
      carried out with HIV patients, aged 18 years or over, attending outpatient
      clinics at the Correia Picanco Hospital/SES/PE and the Oswaldo Cruz/UPE
      University Hospital, who had been recommended to take the TST, in the period
      between November 2007 and February 2010. Univariate and multivariate logistic
      regression analyses were carried out to establish associations between the
      dependent variable - taking the TST (yes/no), at a first stage analysis, and the
      independent variables, followed by a second stage analysis considering a positive
      TST as the dependent variable. The odds ratio was calculated as the measure of
      association and the confidence interval (CI) at 95% as the measure of accuracy of
      the estimate. RESULTS: Of the 2,290 patients recruited, 1087 (47.5%) took the
      TST. Of the 1,087 patients who took the tuberculin skin test, the prevalence of
      TST >= 5 mm was 21.6% among patients with CD4 >= 200 and 9.49% among those with
      CD4 < 200 (p = 0.002). The patients most likely not to take the test were: men,
      people aged under 39 years, people with low educational levels and crack users.
      The risk for not taking the TST was statiscally different for health service.
      Patients who presented better immunity (CD4 >= 200) were more than two and a half
      times more likely to test positive that those with higher levels of
      immunodeficiency (CD4 < 200). CONCLUSIONS: Considering that the TST is
      recommended by the Brazilian health authorities, coverage for taking the test was
      very low. The most serious implication of this is that LTBI treatment was not
      carried out for the unidentified TST-positive patients, who may consequently go
      on to develop TB and eventually die.

PMID- 21892937
TI  - Gene expression study using real-time PCR identifies an NTR gene as a major
      marker of resistance to benzonidazole in Trypanosoma cruzi.
AB  - BACKGROUND: Chagas disease is a neglected illness, with limited treatments,
      caused by the parasite Trypanosoma cruzi. Two drugs are prescribed to treat the
      disease, nifurtimox and benznidazole, which have been previously reported to have
      limited efficacy and the appearance of resistance by T. cruzi. Acquisition of
      drug-resistant phenotypes is a complex physiological process based on single or
      multiple changes of the genes involved, probably in its mechanisms of action.
      RESULTS: The differential genes expression of a sensitive Trypanosoma cruzi
      strain and its induced in vitro benznidazole-resistant phenotypes was studied.
      The stepwise increasing concentration of BZ in the parental strain generated five
      different resistant populations assessed by the IC(50) ranging from 10.49 to 93.7
      MUM. The resistant populations maintained their phenotype when the BZ was
      depleted from the culture for many passages. Additionally, the benznidazole
      resistant phenotypes presented a cross-resistance to nifurtimox but not to G418
      sulfate. On the other hand, four of the five phenotypes resistant to different
      concentrations of drugs had different expression levels for the 12 genes
      evaluated by real-time PCR. However, in the most resistant phenotype (TcR5x), the
      levels of mRNA from these 12 genes and seven more were similar to the parental
      strain but not for NTR and OYE genes, which were down-regulated and over
      expressed, respectively. The number of copies for these two genes was evaluated
      for the parental strain and the TcR5x phenotype, revealing that the NTR gene had
      lost a copy in this last phenotype. No changes were found in the enzyme activity
      of CPR and SOD in the most resistant population. Finally, there was no
      variability of genetic profiles among all the parasite populations evaluated by
      performing low-stringency single-specific primer PCR (LSSP-PCR) and random
      amplified polymorphic DNA RAPD techniques, indicating that no clonal selection or
      drastic genetic changes had occurred for the exposure to BZ. CONCLUSION: Here, we
      propose NTR as the major marker of the appearance of resistance to BZ.

PMID- 21892938
TI  - Ge quantum dot arrays grown by ultrahigh vacuum molecular-beam epitaxy on the
      Si(001) surface: nucleation, morphology, and CMOS compatibility.
AB  - Issues of morphology, nucleation, and growth of Ge cluster arrays deposited by
      ultrahigh vacuum molecular beam epitaxy on the Si(001) surface are considered.
      Difference in nucleation of quantum dots during Ge deposition at low (?600
      degrees C) and high (?600 degrees C) temperatures is studied by high resolution
      scanning tunneling microscopy. The atomic models of growth of both species of Ge
      huts--pyramids and wedges-- are proposed. The growth cycle of Ge QD arrays at low
      temperatures is explored. A problem of lowering of the array formation
      temperature is discussed with the focus on CMOS compatibility of the entire
      process; a special attention is paid upon approaches to reduction of treatment
      temperature during the Si(001) surface pre-growth cleaning, which is at once a
      key and the highest-temperature phase of the Ge/Si(001) quantum dot dense array
      formation process. The temperature of the Si clean surface preparation, the final
      high-temperature step of which is, as a rule, carried out directly in the MBE
      chamber just before the structure deposition, determines the compatibility of
      formation process of Ge-QD-array based devices with the CMOS manufacturing cycle.
      Silicon surface hydrogenation at the final stage of its wet chemical etching
      during the preliminary cleaning is proposed as a possible way of efficient
      reduction of the Si wafer pre-growth annealing temperature.

PMID- 21892939
TI  - Canadian oncogenic human papillomavirus cervical infection prevalence: systematic
      review and meta-analysis.
AB  - BACKGROUND: Oncogenic human papillomavirus (HPV) infection prevalence is required
      to determine optimal vaccination strategies. We systematically reviewed the
      prevalence of oncogenic cervical HPV infection among Canadian females prior to
      immunization. METHODS: We included studies reporting DNA-confirmed oncogenic HPV
      prevalence estimates among Canadian females identified through searching
      electronic databases (e.g., MEDLINE) and public health websites. Two independent
      reviewers screened literature results, abstracted data and appraised study
      quality. Prevalence estimates were meta-analyzed among routine screening
      populations, HPV-positive, and by cytology/histology results. RESULTS: Thirty
      studies plus 21 companion reports were included after screening 837 citations and
      120 full-text articles. Many of the studies did not address non-response bias
      (74%) or use a representative sampling strategy (53%). Age-specific prevalence
      was highest among females aged < 20 years and slowly declined with increasing
      age. Across all populations, the highest prevalence estimates from the meta
      analyses were observed for HPV types 16 (routine screening populations, 8
      studies: 8.6% [95% confidence interval 6.5-10.7%]; HPV-infected, 9 studies: 43.5%
      [28.7-58.2%]; confirmed cervical cancer, 3 studies: 48.8% [34.0-63.6%]) and 18
      (routine screening populations, 8 studies: 3.3% [1.5-5.1%]; HPV-infected, 9
      studies: 13.6% [6.1-21.1%], confirmed cervical cancer, 4 studies: 17.1% [6.4
      27.9%]. CONCLUSION: Our results support vaccinating females < 20 years of age,
      along with targeted vaccination of some groups (e.g., under-screened
      populations). The highest prevalence occurred among HPV types 16 and 18,
      contributing a combined cervical cancer prevalence of 65.9%. Further cancer
      protection is expected from cross-protection of non-vaccine HPV types. Poor study
      quality and heterogeneity suggests that high-quality studies are needed.

PMID- 21892940
TI  - Zebrafish Ext2 is necessary for Fgf and Wnt signaling, but not for Hh signaling.
AB  - BACKGROUND: Heparan sulfate (HS) biosynthesis is tightly regulated during
      vertebrate embryo development. However, potential roles for HS biosynthesis in
      regulating the function of paracrine signaling molecules that bind to HS are
      incompletely understood. RESULTS: In this report we have studied Fgf, Wnt and
      Hedgehog (Hh) signaling in ext2 mutants, where heparan sulfate content is low. We
      found that Fgf targeted gene expression is reduced in ext2 mutants and that the
      remaining expression is readily inhibited by SU5402, an FGF receptor inhibitor.
      In the ext2 mutants, Fgf signaling is shown to be affected during nervous system
      development and reduction of Fgf ligands in the mutants affects tail development.
      Also, Wnt signaling is affected in the ext2 mutants, as shown by a stronger
      phenotype in ext2 mutants injected with morpholinos that partially block
      translation of Wnt11 or Wnt5b, compared to injected wild type embryos. In
      contrast, Hh dependent signaling is apparently unaffected in the ext2 mutants; Hh
      targeted gene expression is not reduced, the Hh inhibitor cyclopamine is not more
      affective in the mutants and Hh dependent cell differentiation in the retina and
      in the myotome are normal in ext2 mutants. In addition, no genetic interaction
      between ext2 and shha during development could be detected. CONCLUSION: We
      conclude that ext2 is involved in Fgf and Wnt signaling but not in Hh signaling,
      revealing an unexpected specificity for ext2 in signaling pathways during
      embryonic development. Thus, our results support the hypothesis that regulation
      of heparan sulfate biosynthesis has distinct instructive functions for different
      signaling factors.

PMID- 21892942
TI  - Evaluation of the nutrition knowledge of sports department students of
      universities.
AB  - BACKGROUND: Individuals who have knowledge on the importance of adequate and
      balanced diet and reflect this knowledge to their behaviors are considered to be
      more successful in sports life. The present study aims to evaluate the nutrition
      knowledge of students receiving sports education in universities. METHODS: The
      study sample consists of 343 voluntary students from the Sports Departments of
      Hacettepe, Gazi and Ankara Universities in Ankara. The questionnaire used in the
      study included a demographic section, and 30 questions on true-false nutrition
      knowledge. For the reliability of the questionnaire, the internal consistency
      coefficient was calculated and the Kuder Richardson (KR-20) value was found to be
      0.71. For higher reliability, 9 dysfunctional questions were excluded from the
      questionnaire. The research data were collected through a questionnaire form and
      face-to-face interviews. For the statistical analyses of the data, tables were
      prepared to show mean, standard deviation (X+/-SD) and percentage (%) values. In
      order to determine the nutrition knowledge of students, the "independent t test"
      was used for nutrition lesson and gender. RESULTS: University students receiving
      sports education and expected to continue their professional lives on sport
      related fields were determined to have the lack of knowledge on nutrition. The
      mean value about the nutrition knowledge of the first year students was found
      11.150 +/- 2.962, while the mean value of the fourth year students was 13.460 +/-
      3.703, and the difference is statistically significant (p = .000). CONCLUSION:
      Students, coaches and teachers in physical education were found not to give the
      necessary importance to their diets, and they were still not aware of the
      importance of nutrition on performance.

PMID- 21892941
TI  - Generating HPV specific T helper cells for the treatment of HPV induced
      malignancies using TCR gene transfer.
AB  - BACKGROUND: Infection with high risk Human Papilloma Virus (HPV) is associated
      with cancer of the cervix, vagina, penis, vulva, anus and some cases of head and
      neck carcinomas. The HPV derived oncoproteins E6 and E7 are constitutively
      expressed in tumor cells and therefore potential targets for T cell mediated
      adoptive immunotherapy. Effective immunotherapy is dependent on the presence of
      both CD4+ and CD8+ T cells. However, low precursor frequencies of HPV16 specific
      T cells in patients and healthy donors hampers routine isolation of these cells
      for adoptive transfer purposes. An alternative to generate HPV specific CD4+ and
      CD8+ T cells is TCR gene transfer. METHODS: HPV specific CD4+ T cells were
      generated using either a MHC class I or MHC class II restricted TCR (from clones
      A9 and 24.101 respectively) directed against HPV16 antigens. Functional analysis
      was performed by interferon-gamma secretion, proliferation and cytokine
      production assays. RESULTS: Introduction of HPV16 specific TCRs into blood
      derived CD4+ recipient T cells resulted in recognition of the relevant HPV16
      epitope as determined by IFN-gamma secretion. Importantly, we also show
      recognition of the endogenously processed and HLA-DP1 presented HPV16E6 epitope
      by 24.101 TCR transgenic CD4+ T cells and recognition of the HLA-A2 presented
      HPV16E7 epitope by A9 TCR transgenic CD4+ T cells. CONCLUSION: Our data indicate
      that TCR transfer is feasible as an alternative strategy to generate human HPV16
      specific CD4+ T helper cells for the treatment of patients suffering from
      cervical cancer and other HPV16 induced malignancies.

PMID- 21892943
TI  - In vivo assessment of catheter positioning accuracy and prolonged irradiation
      time on liver tolerance dose after single-fraction 192Ir high-dose-rate
      brachytherapy.
AB  - BACKGROUND: To assess brachytherapy catheter positioning accuracy and to evaluate
      the effects of prolonged irradiation time on the tolerance dose of normal liver
      parenchyma following single-fraction irradiation with 192Ir. MATERIALS AND
      METHODS: Fifty patients with 76 malignant liver tumors treated by computed
      tomography (CT)-guided high-dose-rate brachytherapy (HDR-BT) were included in the
      study. The prescribed radiation dose was delivered by 1 - 11 catheters with
      exposure times in the range of 844 - 4432 seconds. Magnetic resonance imaging
      (MRI) datasets for assessing irradiation effects on normal liver tissue, edema,
      and hepatocyte dysfunction, obtained 6 and 12 weeks after HDR-BT, were merged
      with 3D dosimetry data. The isodose of the treatment plan covering the same
      volume as the irradiation effect was taken as a surrogate for the liver tissue
      tolerance dose. Catheter positioning accuracy was assessed by calculating the
      shift between the 3D center coordinates of the irradiation effect volume and the
      tolerance dose volume for 38 irradiation effects in 30 patients induced by
      catheters implanted in nearly parallel arrangement. Effects of prolonged
      irradiation were assessed in areas where the irradiation effect volume and
      tolerance dose volume did not overlap (mismatch areas) by using a catheter
      contribution index. This index was calculated for 48 irradiation effects induced
      by at least two catheters in 44 patients. RESULTS: Positioning accuracy of the
      brachytherapy catheters was 5-6 mm. The orthogonal and axial shifts between the
      center coordinates of the irradiation effect volume and the tolerance dose volume
      in relation to the direction vector of catheter implantation were highly
      correlated and in first approximation identically in the T1-w and T2-w MRI
      sequences (p = 0.003 and p < 0.001, respectively), as were the shifts between 6
      and 12 weeks examinations (p = 0.001 and p = 0.004, respectively). There was a
      significant shift of the irradiation effect towards the catheter entry site
      compared with the planned dose distribution (p < 0.005). Prolonged treatment time
      increases the normal tissue tolerance dose. Here, the catheter contribution
      indices indicated a lower tolerance dose of the liver parenchyma in areas with
      prolonged irradiation (p < 0.005). CONCLUSIONS: Positioning accuracy of
      brachytherapy catheters is sufficient for clinical practice. Reduced tolerance
      dose in areas exposed to prolonged irradiation is contradictory to results
      published in the current literature. Effects of prolonged dose administration on
      the liver tolerance dose for treatment times of up to 60 minutes per HDR-BT
      session are not pronounced compared to effects of positioning accuracy of the
      brachytherapy catheters and are therefore of minor importance in treatment
      planning.

PMID- 21892944
TI  - Volumetric modulated arc therapy is superior to conventional intensity modulated
      radiotherapy--a comparison among prostate cancer patients treated in an
      Australian centre.
AB  - BACKGROUND: Radiotherapy technology is expanding rapidly. Volumetric Modulated
      Arc Therapy (VMAT) technologies such as RapidArc(r) (RA) may be a more efficient
      way of delivering intensity-modulated radiotherapy-like (IM) treatments. This
      study is an audit of the RA experience in an Australian department with a
      planning and economic comparison to IM. METHODS: 30 consecutive prostate cancer
      patients treated radically with RA were analyzed. Eight RA patients treated
      definitively were then completely re-planned with 3D conformal radiotherapy (3D);
      and a conventional sliding window IM technique; and a new RA plan. The acceptable
      plans and their treatment times were compared and analyzed for any significant
      difference. Differences in staff costs of treatment were computed and analyzed.
      RESULTS: Thirty patients had been treated to date with eight being treated
      definitely to at least 74 Gy, nine post high dose brachytherapy (HDR) to 50.4Gy
      and 13 post prostatectomy to at least 64Gy. All radiotherapy courses were
      completed with no breaks. Acute rectal toxicity by the RTOG criteria was
      acceptable with 22 having no toxicity, seven with grade 1 and one had grade 2.Of
      the eight re-planned patients, none of the 3D (three-dimensional conformal
      radiotherapy) plans were acceptable based on local guidelines for dose to organs
      at risk. There was no statistically significant difference in planning times
      between IM and RA (p = 0.792). IM had significantly greater MUs per fraction
      (1813.9 vs 590.2 p < 0.001), total beam time per course (5.2 vs 3.1 hours, p =
      0.001) and average treatment staff cost per patient radiotherapy course
      ($AUD489.91 vs $AUD315.66, p = 0.001). The mean saving in treatment staff cost
      for RA treatment was $AUD174.25 per patient. CONCLUSIONS: 3D was incapable of
      covering a modern radiotherapy volume for the radical treatment of prostate
      cancer. These volumes can be treated via conventional IM and RA. RA was
      significantly more efficient, safe and cost effective than IM. VMAT technologies
      are a superior way of delivering IM-like treatments.

PMID- 21892945
TI  - Understanding of and adherence to advice after telephone counselling by nurse: a
      survey among callers to a primary emergency out-of-hours service in Norway.
AB  - BACKGROUND: To investigate how callers understand the information given by
      telephone by registered nurses in a casualty clinic, to what degree the advice
      was followed, and the final outcome of the condition for the patients. METHODS:
      The study was conducted at a large out-of-hours inter-municipality casualty
      clinic in Norway during April and May 2010. Telephone interviews were performed
      with 100 callers/patients who had received information and advice by a nurse as a
      sole response. Six topics from the interview guide were compared with the
      telephone record files to check whether the caller had understood the advice. In
      addition, questions were asked about how the caller followed the advice provided
      and the patient's outcome. RESULTS: 99 out of 100 interviewed callers stated that
      they had understood the nurse's advice, but interpreted from the telephone
      records, the total agreement for all six topics was 82.6%. 93 callers/patients
      stated that they followed the advice and 11 re-contacted the casualty clinic. 22
      contacted their GP for the same complaints the same week, of whom five patients
      received medical treatment and one was hospitalised. There were significant
      difference between the native-Norwegian and the non-native Norwegian regarding
      whether they trusted the nurse (p = 0.017), and if they got relevant answers to
      their questions (p = 0.005). CONCLUSION: Callers to the out-of-hours service seem
      to understand the advice given by the registered nurses, and a large majority of
      the patients did not contact their GP or other health services again with the
      same complaints. PRACTICE IMPLICATION: Medical and communicative training must be
      an important part of the continuous improvement strategy within the out-of-hour
      services.

PMID- 21892946
TI  - Can we use the pharmacy data to estimate the prevalence of chronic conditions? a
      comparison of multiple data sources.
AB  - BACKGROUND: The estimate of the prevalence of the most common chronic conditions
      (CCs) is calculated using direct methods such as prevalence surveys but also
      indirect methods using health administrative databases.The aim of this study is
      to provide estimates prevalence of CCs in Lazio region of Italy (including Rome),
      using the drug prescription's database and to compare these estimates with those
      obtained using other health administrative databases. METHODS: Prevalence of CCs
      was estimated using pharmacy data (PD) using the Anathomical Therapeutic Chemical
      Classification System (ATC).Prevalences estimate were compared with those
      estimated by hospital information system (HIS) using list of ICD9-CM diagnosis
      coding, registry of exempt patients from health care cost for pathology (REP) and
      national health survey performed by the Italian bureau of census (ISTAT).
      RESULTS: From the PD we identified 20 CCs. About one fourth of the population
      received a drug for treating a cardiovascular disease, 9% for treating a
      rheumatologic conditions.The estimated prevalences using the PD were usually
      higher that those obtained with one of the other sources. Regarding the
      comparison with the ISTAT survey there was a good agreement for cardiovascular
      disease, diabetes and thyroid disorder whereas for rheumatologic conditions,
      chronic respiratory illnesses, migraine and Alzheimer's disease, the prevalence
      estimates were lower than those estimated by ISTAT survey. Estimates of
      prevalences derived by the HIS and by the REP were usually lower than those of
      the PD (but malignancies, chronic renal diseases). CONCLUSION: Our study showed
      that PD can be used to provide reliable prevalence estimates of several CCs in
      the general population.

PMID- 21892947
TI  - Multiple right-sided pulmonary nodules: metastatic cancer or resectable early
      stage tumor?
AB  - The aim of this paper is to focus attention on complex cases of lung disease that
      may benefit from being managed outside formal guidelines. A 52 year-old man who
      had previously undergone a laryngectomy for squamous cell carcinoma, presented
      with a 1.2 cm nodule in the right upper pulmonary lobe. Three months later a new
      CT scan found that the nodule had slightly increased in size and also detected
      two new smaller nodules in the middle lobe. A PET/CT scan showed metabolic
      hyperactivity of all nodules. Since needle aspiration of the upper one revealed
      malignant cells, the patient was considered to be suffering from metastatic
      cancer and started on chemotherapy. At follow-up both CT and PET scans found a
      significant reduction in volume and activity of the lower nodules but no change
      in the upper one. At diagnostic thoracoscopy, histology demonstrated that the
      upper nodule was an adenocarcinoma while the lower ones were inflammatory. An
      upper lobectomy and systematic nodal dissection were therefore performed.
      Histology established a diagnosis of upper pulmonary adenocarcinoma and
      sarcoidosis. Our report suggests that in complicated oncologic cases in which non
      invasive diagnostic tools yield incongruous results surgery should be considered
      without delay.

PMID- 21892948
TI  - Early onset sebaceous carcinoma.
AB  - BACKGROUND: Ocular sebaceous carcinoma can masquerade as benign lesions resulting
      in delay of diagnosis. Early recognition is even more difficult in young patients
      where the disease rarely occurs. Here, we provide a clinicopathological
      correlation of ocular sebaceous carcinoma in a young individual lacking history
      of hereditary cancer or immunosuppression. FINDINGS: A detailed histopathological
      study including p53 DNA sequencing was performed on an aggressive sebaceous
      carcinoma presenting in a healthy 32 year-old Caucasian woman. She had no history
      of retinoblastoma, evidence for a hereditary cancer syndrome, or radiation
      therapy. However, she potentially was at risk for excessive UV light exposure. A
      detailed review of the literature is also provided.A moderately well
      differentiated sebaceous carcinoma was established histopathologically arising
      from the meibomian gland of the upper eyelid. In most areas, the cytoplasm
      contained small but distinct Oil-red-O positive vacuoles. Direct sequencing of
      p53 identified a G:C->A:T mutation at a dipyrimidine site. The mutation results
      in substitution of arginine for the highly conserved glycine at residue 199
      located at the p53 dimer-dimer interface. Energy minimization structural modeling
      predicts that G199R will neutralize negative charges contributed by nearby inter-
      and intramonomeric glutamate residues. DISCUSSION: This study points to the
      importance of recognizing that sebaceous carcinoma can occur in young patients
      with no evidence for hereditary cancer risk or radiation therapy. The G199R
      substitution is anticipated to alter the stability of the p53 tetrameric complex.
      The role of UV light in the etiology of sebaceous carcinoma deserves further
      study. Our findings, taken together with those of others, suggest that different
      environmental factors could lead to the development of sebaceous carcinoma in
      different patients.

PMID- 21892949
TI  - Telemetric left ventricular monitoring using wireless telemetry in the rabbit
      model.
AB  - BACKGROUND: Heart failure is a critical condition that affects many people and
      often results from left ventricular dysfunction. Numerous studies investigating
      this condition have been performed using various model systems. To do so,
      investigators must be able to accurately measure myocardial performance in order
      to determine the degree of left ventricular function. In this model development
      study, we employ a wireless telemetry system purchased from Data Sciences
      International to continuously assess left ventricular function in the rabbit
      model. FINDINGS: We surgically implanted pressure-sensitive catheters fitted to
      wireless radio-transmitters into the left ventricle of Dutch-belted rabbits.
      Following recovery of the animals, we continuously recorded indices of cardiac
      contractility and ventricular relaxation at baseline for a given time period. The
      telemetry system allowed us to continuously record baseline left ventricular
      parameters for the entire recording period. During this time, the animals were
      unrestrained and fully conscious. The values we recorded are similar to those
      obtained using other reported methods. CONCLUSIONS: The wireless telemetry system
      can continuously measure left ventricular pressure, cardiac contractility, and
      cardiac relaxation in the rabbit model. These results, which were obtained just
      as baseline levels, substantiate the need for further validation in this model
      system of left ventricular assessment.

PMID- 21892950
TI  - Post-transplant lymphoproliferative disorders and Epstein-Barr virus DNAemia in a
      cohort of lung transplant recipients.
AB  - BACKGROUND: Post-transplant lymphoproliferative disorders (PTLD) are serious
      complications in lung transplant recipients. No consensus on EBV DNAemia levels
      predictive of PTLD has been reached. In addition, in many instances EBV DNAemia
      is determined in patients with suggestive symptoms only. METHODS: The
      characteristics of five patients with PTLD as well as the prevalence of EBV
      DNAmia in a cohort of 137 consecutive patients receiving lung transplantation are
      described. RESULTS: Twenty-six out of 137 patients (18.9%) were excluded from the
      analysis because lost at follow-up or dead from PTLD-independent reasons within
      three months of transplantation. EBV DNA in peripheral blood mononuclear cells
      (PBMC) was determined in 83/111 patients (74.8%) because of potential PTLD
      related symptoms, while 28 patients (25.2%) showed no symptoms and were not
      examined. EBV DNAemia was positive in 53/83 patients (63.8%), and negative in
      30/83 patients (36.2%). PTLD was diagnosed in five (4.5%) patients at a median
      time of 270 (range 120-870) days following transplantation. All five PTLD (three
      large B-cell lymphomas, one Hodgkin lymphoma and one possible pre-neoplastic
      lesion) were potentially associated with EBV infection. However, only 3/5
      patients with PTLD had detectable EBV DNAemia: < 1,000 copies EBV DNA/1 * 105
      PBMC in one patient and > 1,000 copies EBV DNA/1 * 105 PBMC in two patients.
      CONCLUSION: A systematic multidisciplinary (clinical, radiologic, virologic and
      histologic) approach is mandatory for the diagnosis and management of PTLD in
      lung transplant recipients, while monitoring of symptomatic patients only may
      provide an incomplete or late picture of the clinical problem. In addition,
      staining for EBV antigens and quantification of EBV DNA in biopsy specimens
      should always be performed to understand the role of EBV infection in the
      pathogenesis of PTLD.

PMID- 21892951
TI  - Carbohydrate-active enzymes from pigmented Bacilli: a genomic approach to assess
      carbohydrate utilization and degradation.
AB  - BACKGROUND: Spore-forming Bacilli are gram-positive bacteria commonly found in a
      variety of natural habitats, including soil, water and the gastro-intestinal (GI)
      tract of animals. Isolates of various Bacillus species produce pigments, mostly
      carotenoids, with a putative protective role against UV irradiation and oxygen
      reactive forms. RESULTS: We report the annotation of carbohydrate active enzymes
      (CAZymes) of two pigmented Bacilli isolated from the human GI-tract and belonging
      to the Bacillus indicus and B. firmus species. A high number of glycoside
      hydrolases (GHs) and carbohydrate binding modules (CBMs) were found in both
      isolates. A detailed analysis of CAZyme families, was performed and supported by
      growth data. Carbohydrates able to support growth as the sole carbon source
      negatively effected carotenoid formation in rich medium, suggesting that a
      catabolite repression-like mechanism controls carotenoid biosynthesis in both
      Bacilli. Experimental results on biofilm formation confirmed genomic data on the
      potentials of B. indicus HU36 to produce a levan-based biofilm, while mucin
      binding and -degradation experiments supported genomic data suggesting the
      ability of both Bacilli to degrade mammalian glycans. CONCLUSIONS: CAZy analyses
      of the genomes of the two pigmented Bacilli, compared to other Bacillus species
      and validated by experimental data on carbohydrate utilization, biofilm formation
      and mucin degradation, suggests that the two pigmented Bacilli are adapted to the
      intestinal environment and are suited to grow in and colonize the human gut.

PMID- 21892952
TI  - A protocol for the emergency department management of acute undifferentiated
      febrile illness in India.
AB  - BACKGROUND: Fever is a common presenting complaint in the developing world, but
      there is a paucity of literature to guide investigation and treatment of the
      adult patient presenting with fever and no localizing symptoms. OBJECTIVE: The
      objective of this study was to devise a standardized protocol for the evaluation
      and treatment of febrile adult patients who have no localizing symptoms in order
      to reduce unnecessary testing and inappropriate antimicrobial use. After devising
      the protocol, a pilot study was performed to assess its feasibility in the
      emergency department. METHODS: A protocol was formulated for adult patients
      presenting with fever who had no clinical evidence of sepsis and no localizing
      symptoms to suggest the etiology of their fever. Investigations were based on
      duration of fever with no investigations indicated prior to day 3. Treatment was
      guided by results of investigations. A pilot study was performed after protocol
      implementation, wherein data were collected on successive adult patients
      presenting with fever. RESULTS: During the 6-week study period, 342 patients
      presented with fever, 209 of whom fit the parameters of the protocol, with 113 of
      these patients presenting on the 1st or 2nd day of fever. All patients
      experienced defervescence of fever, with ten patients being lost to follow-up. Of
      the patients presenting on day 1 or 2 of fever, 75.2% (85/113) defervesced
      without the need for testing; 53.1% (60/113) experienced defervescence without
      the need for antimicrobial therapy. CONCLUSION: Implementation of this rational,
      standardized protocol for the assessment and treatment of stable adult patients
      presenting with acute undifferentiated febrile illness can lead to reduced rates
      of testing and antimicrobial use. A prospective, controlled trial will be
      required to confirm these findings and to assess additional safety outcome
      measures.

PMID- 21892953
TI  - Rapid assessment of myocardial infarct size in rodents using multi-slice
      inversion recovery late gadolinium enhancement CMR at 9.4T.
AB  - BACKGROUND: Myocardial infarction (MI) can be readily assessed using late
      gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR). Inversion
      recovery (IR) sequences provide the highest contrast between enhanced infarct
      areas and healthy myocardium. Applying such methods to small animals is
      challenging due to rapid respiratory and cardiac rates relative to T1 relaxation.
      METHODS: Here we present a fast and robust protocol for assessing LGE in small
      animals using a multi-slice IR gradient echo sequence for efficient assessment of
      LGE. An additional Look-Locker sequence was used to assess the optimum inversion
      point on an individual basis and to determine most appropriate gating points for
      both rat and mouse. The technique was applied to two preclinical scenarios: i) an
      acute (2 hour) reperfused model of MI in rats and ii) mice 2 days following non
      reperfused MI. RESULTS: LGE images from all animals revealed clear areas of
      enhancement allowing for easy volume segmentation. Typical inversion times
      required to null healthy myocardium in rats were between 300-450 ms equivalent to
      2-3 R-waves and ~330 ms in mice, typically 3 R-waves following inversion. Data
      from rats was also validated against triphenyltetrazolium chloride staining and
      revealed close agreement for infarct size. CONCLUSION: The LGE protocol presented
      provides a reliable method for acquiring images of high contrast and quality
      without excessive scan times, enabling higher throughput in experimental studies
      requiring reliable assessment of MI.

PMID- 21892954
TI  - Older People's Quality of Life (OPQOL) scores and adverse health outcomes at a
      one-year follow-up. A prospective cohort study on older outpatients living in the
      community in Italy.
AB  - BACKGROUND: There is limited knowledge on the ability of a poor quality of life
      (QOL) and health-related QOL (HRQOL) to predict mortality and other adverse
      health events, independently of the frailty syndrome and other confounders, in
      older people living in the community and not selected on the basis of specific
      chronic conditions. Aim of this study was to evaluate the ability of the overall
      QOL and of the HRQOL to predict several adverse health outcomes at a one-year
      follow-up in an older outpatient population living in the community. METHODS: We
      carried out a prospective cohort study on 210 community-dwelling outpatients aged
      65+ (mean age 81.2 yrs) consecutively referred to a geriatric clinic in Milan,
      Italy. At baseline participants underwent a comprehensive geriatric assessment
      including evaluation of overall QOL and HRQOL by means of the Older People's
      Quality of Life (OPQOL) questionnaire. At a one-year follow-up, between June and
      December 2010, we investigated nursing home placement and death in all 210
      participants as well as any fall, any admission to the emergency department (ED),
      any hospitalisation and greater functional dependence among the subset of
      subjects still living at home. RESULTS: One year after the visit 187 subjects
      were still living at home (89%) while 7 had been placed in a nursing home (3.3%)
      and 16 had died (7.7%). At multiple logistic regression analyses the lowest score
      based quartile of the OPQOL total score at baseline was independently associated
      with a greater risk of any fall and any ED admission. Also, the lowest score
      based quartile of the health-related OPQOL sub-score was associated with a
      greater risk of any fall as well as of nursing home placement (odds ratio [OR]
      10.03, 95% confidence interval [CI] 1.25-80.54, P = 0.030) and death (OR 4.23,
      95% CI 1.06-16.81, P = 0.041). The correlation with the latter two health
      outcomes was found after correction for age, sex, education, income, living
      conditions, comorbidity, disability and the frailty syndrome. CONCLUSIONS: In an
      older outpatient population in Italy the OPQOL total score and its health-related
      sub-score were independent predictors of several adverse health outcomes at one
      year. Notably, poor HRQOL predicted both nursing home placement and death even
      after correction for the frailty syndrome. These findings support and enhance the
      prognostic relevance of QOL measures.

PMID- 21892955
TI  - Trends in reported AIDS defining illnesses (ADIs) among participants in a
      universal antiretroviral therapy program: an observational study.
AB  - BACKGROUND: We examined trends in AIDS-defining illnesses (ADIs) among
      individuals receiving highly active antiretroviral therapy (HAART) in British
      Columbia (BC), Canada to determine whether declines in ADIs could be contributing
      to previously observed improvements in life-expectancy among HAART patients in BC
      since 1996. METHODS: HAART-naive individuals aged >= 18 years who initiated
      treatment in BC each of the following time-periods 1996 - 1998; 1999 - 2001; 2002
      - 2004; 2005 - 2007 were included. The proportion of participants with reported
      ADIs were examined for each time period and trends were analyzed using the
      Cochran-Armitage Trend Test. Cox proportional hazards models were used to examine
      factors associated with ADIs. RESULTS: A total of 3721 individuals (81% male)
      initiated HAART during the study period. A total of 251 reports of ADIs were
      received from 214 unique patients. These occurred in a median of 4 months (IQR =
      1-19 months) from HAART initiation. The proportion of individuals with a reported
      ADI did not change significantly from 4.6% in the earliest time period to 5.8% in
      the latest period (p = 0.181 for test of trend). There were no significant
      declines in any specific ADI over the study period. Multivariable Cox models
      found that individuals initiating HAART during 2002-04 were at an increased risk
      of ADIs (AHR = 1.55; 95% CI 1.04-2.32) in comparison to 1996 - 98, but there were
      no significant differences in other time periods. CONCLUSIONS: Trends in reported
      ADIs among individuals receiving HAART since 1996 in BC do not appear to parallel
      improvements in life-expectancy over the same period.

PMID- 21892956
TI  - Enhancing measurement of primary health care indicators using an equity lens: An
      ethnographic study.
AB  - INTRODUCTION: One important goal of strengthening and renewal in primary
      healthcare (PHC) is achieving health equity, particularly for vulnerable
      populations. There has been a flurry of international activity toward the
      establishment of indicators relevant to measuring and monitoring PHC. Yet, little
      attention has been paid to whether current indicators: 1) are sensitive enough to
      detect inequities in processes or outcomes of care, particularly in relation to
      the health needs of vulnerable groups or 2) adequately capture the complexity of
      delivering PHC services across diverse groups. The purpose of this paper is to
      contribute to the discourse regarding what ought to be considered a PHC indicator
      and to provide some concrete examples illustrating the need for modification and
      development of new indicators given the goal of PHC achieving health equity.
      METHODS: Within the context of a larger study of PHC delivery at two Health
      Centers serving people facing multiple disadvantages, a mixed methods
      ethnographic design was used. Three sets of data collected included: (a)
      participant observation data focused on the processes of PHC delivery, (b)
      interviews with Health Center staff, and (c) interviews with patients. RESULTS:
      Thematic analysis suggests there is a disjuncture between clinical work
      addressing the complex needs of patients facing multiple vulnerabilities such as
      extreme levels of poverty, multiple chronic conditions, and lack of housing and
      extant indicators and how they are measured. Items could better measure and
      monitor performance at the management level including, what is delivered (e.g.,
      focus on social determinants of health) and how services are delivered to
      socially disadvantaged populations (e.g., effective use of space, expectation for
      all staff to have welcoming and mutually respectful interactions). New indicators
      must be developed to capture inputs (e.g., stability of funding sources) and
      outputs (e.g., whole person care) in ways that better align with care provided to
      marginalized populations. CONCLUSIONS: The current emphasis on achieving greater
      equity through PHC, the continued calls for the renewal and strengthening of PHC,
      and the use of monitoring and performance indicators highlight the relevance of
      ensuring that there are more accurate methods to capture the complex work of PHC
      organizations.

PMID- 21892958
TI  - Impact of pretreatment and downstream processing technologies on economics and
      energy in cellulosic ethanol production.
AB  - BACKGROUND: While advantages of biofuel have been widely reported, studies also
      highlight the challenges in large scale production of biofuel. Cost of ethanol
      and process energy use in cellulosic ethanol plants are dependent on technologies
      used for conversion of feedstock. Process modeling can aid in identifying techno
      economic bottlenecks in a production process. A comprehensive techno-economic
      analysis was performed for conversion of cellulosic feedstock to ethanol using
      some of the common pretreatment technologies: dilute acid, dilute alkali, hot
      water and steam explosion. Detailed process models incorporating feedstock
      handling, pretreatment, simultaneous saccharification and co-fermentation,
      ethanol recovery and downstream processing were developed using SuperPro
      Designer. Tall Fescue (Festuca arundinacea Schreb) was used as a model feedstock.
      RESULTS: Projected ethanol yields were 252.62, 255.80, 255.27 and 230.23 L/dry
      metric ton biomass for conversion process using dilute acid, dilute alkali, hot
      water and steam explosion pretreatment technologies respectively. Price of
      feedstock and cellulose enzymes were assumed as $50/metric ton and 0.517/kg broth
      (10% protein in broth, 600 FPU/g protein) respectively. Capital cost of ethanol
      plants processing 250,000 metric tons of feedstock/year was $1.92, $1.73, $1.72
      and $1.70/L ethanol for process using dilute acid, dilute alkali, hot water and
      steam explosion pretreatment respectively. Ethanol production cost of $0.83,
      $0.88, $0.81 and $0.85/L ethanol was estimated for production process using
      dilute acid, dilute alkali, hot water and steam explosion pretreatment
      respectively. Water use in the production process using dilute acid, dilute
      alkali, hot water and steam explosion pretreatment was estimated 5.96, 6.07, 5.84
      and 4.36 kg/L ethanol respectively. CONCLUSIONS: Ethanol price and energy use
      were highly dependent on process conditions used in the ethanol production plant.
      Potential for significant ethanol cost reductions exist in increasing pentose
      fermentation efficiency and reducing biomass and enzyme costs. The results
      demonstrated the importance of addressing the tradeoffs in capital costs,
      pretreatment and downstream processing technologies.

PMID- 21892957
TI  - Analysis of an ankyrin-like region in Epstein Barr Virus encoded (EBV) BZLF-1
      (ZEBRA) protein: implications for interactions with NF-kappaB and p53.
AB  - BACKGROUND: The carboxyl terminal of Epstein-Barr virus (EBV) ZEBRA protein (also
      termed BZLF-1 encoded replication protein Zta or ZEBRA) binds to both NF-kappaB
      and p53. The authors have previously suggested that this interaction results from
      an ankyrin-like region of the ZEBRA protein since ankyrin proteins such as
      IkappaB interact with NF-kappaB and p53 proteins. These interactions may play a
      role in immunopathology and viral carcinogenesis in B lymphocytes as well as
      other cell types transiently infected by EBV such as T lymphocytes, macrophages
      and epithelial cells. METHODS: Randomization of the ZEBRA terminal amino acid
      sequence followed by statistical analysis suggest that the ZEBRA carboxyl
      terminus is most closely related to ankyrins of the invertebrate cactus IkappaB
      like protein. This observation is consistent with an ancient origin of ZEBRA
      resulting from a recombination event between an ankyrin regulatory protein and a
      fos/jun DNA binding factor. In silico modeling of the partially solved ZEBRA
      carboxyl terminus structure using PyMOL software demonstrate that the carboxyl
      terminus region of ZEBRA can form a polymorphic structure termed ZANK (ZEBRA
      ANKyrin-like region) similar to two adjacent IkappaB ankyrin domains.
      CONCLUSIONS: Viral capture of an ankyrin-like domain provides a mechanism for
      ZEBRA binding to proteins in the NF-kappaB and p53 transcription factor families,
      and also provides support for a process termed "Ping-Pong Evolution" in which DNA
      viruses such as EBV are formed by exchange of information with the host genome.
      An amino acid polymorphism in the ZANK region is identified in ZEBRA from tumor
      cell lines including Akata that could alter binding of Akata ZEBRA to the p53
      tumor suppressor and other ankyrin binding protein, and a novel model of
      antagonistic binding interactions between ZANK and the DNA binding regions of
      ZEBRA is suggested that may be explored in further biochemical and molecular
      biological models of viral replication.

PMID- 21892959
TI  - Econobiophysics - game of choosing. Model of selection or election process with
      diverse accessible information.
AB  - We propose several models applicable to both selection and election processes
      when each selecting or electing subject has access to different information about
      the objects to choose from. We wrote special software to simulate these
      processes. We consider both the cases when the environment is neutral (natural
      process) as well as when the environment is involved (controlled process).

PMID- 21892960
TI  - The clinical assessment study of the foot (CASF): study protocol for a
      prospective observational study of foot pain and foot osteoarthritis in the
      general population.
AB  - BACKGROUND: Symptomatic osteoarthritis (OA) affects approximately 10% of adults
      aged over 60 years. The foot joint complex is commonly affected by OA, yet there
      is relatively little research into OA of the foot, compared with other frequently
      affected sites such as the knee and hand. Existing epidemiological studies of
      foot OA have focussed predominantly on the first metatarsophalangeal joint at the
      expense of other joints. This three-year prospective population-based
      observational cohort study will describe the prevalence of symptomatic
      radiographic foot OA, relate its occurrence to symptoms, examination findings and
      life-style-factors, describe the natural history of foot OA, and examine how it
      presents to, and is diagnosed and managed in primary care. METHODS: All adults
      aged 50 years and over registered with four general practices in North
      Staffordshire, UK, will be invited to participate in a postal Health Survey
      questionnaire. Respondents to the questionnaire who indicate that they have
      experienced foot pain in the preceding twelve months will be invited to attend a
      research clinic for a detailed clinical assessment. This assessment will consist
      of: clinical interview; physical examination; digital photography of both feet
      and ankles; plain x-rays of both feet, ankles and hands; ultrasound examination
      of the plantar fascia; anthropometric measurement; and a further self-complete
      questionnaire. Follow-up will be undertaken in consenting participants by postal
      questionnaire at 18 months (clinic attenders only) and three years (clinic
      attenders and survey participants), and also by review of medical records.
      DISCUSSION: This three-year prospective epidemiological study will combine survey
      data, comprehensive clinical, x-ray and ultrasound assessment, and review of
      primary care records to identify radiographic phenotypes of foot OA in a
      population of community-dwelling older adults, and describe their impact on
      symptoms, function and clinical examination findings, and their presentation,
      diagnosis and management in primary care.

PMID- 21892961
TI  - Beneficial effects of physical activity in an HIV-infected woman with
      lipodystrophy: a case report.
AB  - INTRODUCTION: Lipodystrophy is common in patients infected with human
      immunodeficiency virus receiving highly active antiretroviral therapy, and
      presents with morphologic changes and metabolic alterations that are associated
      with depressive behavior and reduced quality of life. We examined the effects of
      exercise training on morphological changes, lipid profile and quality of life in
      a woman with human immunodeficiency virus presenting with lipodystrophy. CASE
      PRESENTATION: A 31-year-old Latin-American Caucasian woman infected with human
      immunodeficiency virus participated in a 12-week progressive resistance exercise
      training program with an aerobic component. Her weight, height, skinfold
      thickness, body circumferences, femur and humerus diameter, blood lipid profile,
      maximal oxygen uptake volume, exercise duration, strength and quality of life
      were assessed pre-exercise and post-exercise training. After 12 weeks, she
      exhibited reductions in her total subcutaneous fat (18.5%), central subcutaneous
      fat (21.0%), peripheral subcutaneous fat (10.7%), waist circumference (WC)
      (4.5%), triglycerides (9.9%), total cholesterol (12.0%) and low-density
      lipoprotein cholesterol (8.6%). She had increased body mass (4.6%), body mass
      index (4.37%), humerus and femur diameter (3.0% and 2.3%, respectively), high
      density lipoprotein cholesterol (16.7%), maximal oxygen uptake volume (33.3%),
      exercise duration (37.5%) and strength (65.5%). Quality of life measures improved
      mainly for psychological and physical measures, independence and social
      relationships. CONCLUSIONS: These findings suggest that supervised progressive
      resistance exercise training is a safe and effective treatment for evolving
      morphologic and metabolic disorders in adults infected with HIV receiving highly
      active antiretroviral therapy, and improves their quality of life.

PMID- 21892962
TI  - Low plasma progranulin levels in children with autism.
AB  - BACKGROUND: Autoimmunity to brain may play a pathogenic role in autism. In
      autoimmune disorders, the formation of antigen-antibody complexes triggers an
      inflammatory response by inducing the infiltration of neutrophils. Local
      administration of recombinant progranulin, which is an anti-inflammatory
      neurotrophic factor, potently inhibit neutrophilic inflammation in vivo,
      demonstrating that progranulin represents a crucial inflammation-suppressing
      mediator. We are the first to measure plasma progranulin levels in autism.
      METHODS: Plasma levels of progranulin were measured, by ELISA, in 40 autistic
      patients, aged between 3 and 12 years, and 40 healthy-matched children. RESULTS:
      Autistic children had significantly lower plasma progranulin levels, P = 0.001.
      Reduced plasma progranulin levels were found in 65% (26/40) of autistic
      children.On the other hand, there was a non significant difference between plasma
      progranulin levels of children with mild to moderate autism and patients with
      severe autism, P = 0.11. CONCLUSIONS: Plasma progranulin levels were reduced in a
      subgroup of patients with autism. Progranulin insufficiency in some patients with
      autism may result in many years of reduced neutrotrophic support together with
      cumulative damage in association with dysregulated inflammation that may have a
      role in autism. However, these data should be treated with caution until further
      investigations are performed, with a larger subject population, to determine
      whether the decrease of plasma progranulin levels is a mere consequence of autism
      or has a pathogenic role in the disease. The role of progranulin therapy should
      also be studied in autism.

PMID- 21892963
TI  - Chromatin regulated interchange between polycomb repressive complex 2 (PRC2)-Ezh2
      and PRC2-Ezh1 complexes controls myogenin activation in skeletal muscle cells.
AB  - BACKGROUND: Polycomb group (PcG) genes code for chromatin multiprotein complexes
      that are responsible for maintaining gene silencing of transcriptional programs
      during differentiation and in adult tissues. Despite the large amount of
      information on PcG function during development and cell identity homeostasis,
      little is known regarding the dynamics of PcG complexes and their role during
      terminal differentiation. RESULTS: We show that two distinct polycomb repressive
      complex (PRC)2 complexes contribute to skeletal muscle cell differentiation: the
      PRC2-Ezh2 complex, which is bound to the myogenin (MyoG) promoter and muscle
      creatine kinase (mCK) enhancer in proliferating myoblasts, and the PRC2-Ezh1
      complex, which replaces PRC2-Ezh2 on MyoG promoter in post-mitotic myotubes.
      Interestingly, the opposing dynamics of PRC2-Ezh2 and PRC2-Ezh1 at these muscle
      regulatory regions is differentially regulated at the chromatin level by Msk1
      dependent methyl/phospho switch mechanism involving phosphorylation of serine 28
      of the H3 histone (H3S28ph). While Msk1/H3S28ph is critical for the displacement
      of the PRC2-Ezh2 complex, this pathway does not influence the binding of PRC2
      Ezh1 on the chromatin. Importantly, depletion of Ezh1 impairs muscle
      differentiation and the chromatin recruitment of MyoD to the MyoG promoter in
      differentiating myotubes. We propose that PRC2-Ezh1 is necessary for controlling
      the proper timing of MyoG transcriptional activation and thus, in contrast to
      PRC2-Ezh2, is required for myogenic differentiation. CONCLUSIONS: Our data reveal
      another important layer of epigenetic control orchestrating skeletal muscle cell
      terminal differentiation, and introduce a novel function of the PRC2-Ezh1 complex
      in promoter setting.

PMID- 21892964
TI  - Does market exclusivity hinder the development of Follow-on Orphan Medicinal
      Products in Europe?
AB  - BACKGROUND: We determined whether the market exclusivity incentive of the
      European Orphan Drug Regulation results in a market monopoly or that absence of
      another Orphan Medicinal Product (OMP) for the same rare disorder, a so-called
      follow-on OMP, is a matter of time or market size. In the interest of rare
      disorder patients better understanding of the effect of the market exclusivity
      incentive on follow-on OMP development is warranted. METHODS: First, the impact
      of various market-, product- and disease-related characteristics on follow-on OMP
      development in the EU was determined by comparing rare disorders with an approved
      OMP and at least one follow-on OMP (N = 26), with rare disorders with an approved
      OMP and no follow-on OMP (N = 18). Next, we determined whether manufacturers
      continued development of a follow-on OMP upon approval of the first OMP for the
      intended rare disorder. Since in the EU significant benefit of an OMP has to be
      established, we determined for each follow-on OMP for which development was
      continued on what grounds significant benefit was assumed by the sponsor. Data
      were collected from the public domain only. RESULTS: The likelihood of a rare
      disorder with an approved OMP to obtain at least one follow-on OMP development
      was strongly associated with disease prevalence, turnover of the first OMP,
      disease class, disease-specific scientific output and age of onset. Out of a
      total of 120 follow-on OMPs only one follow-on OMP could be identified for which
      development was discontinued upon approval of the first OMP for the same rare
      disorder. Only a substantial level of discontinuation of follow-on OMP
      development would have indicated the existence of a market monopoly. Moreover,
      sponsors that continued development of a follow-on OMP predominantly assumed that
      their product had an improved efficacy compared to the first approved OMP.
      CONCLUSIONS: This study provides evidence that absence of follow-on OMP
      development is a matter of time or market size, rather than that the market
      exclusivity incentive of the European Orphan Drug Regulation creates a market
      monopoly.

PMID- 21892965
TI  - Thyroid-stimulating hormone elevation misdiagnosed as subclinical hypothyroidism
      following non-convulsive status epilepticus: a case report.
AB  - INTRODUCTION: Non-convulsive status epilepticus is a form of epileptic seizure
      that occurs without convulsions. Recent reviews suggest that the diagnosis of non
      convulsive status epilepticus remains difficult. Here, we report the case of a
      patient with thyroid-stimulating hormone elevation misdiagnosed as subclinical
      hypothyroidism following non-convulsive status epilepticus. CASE PRESENTATION:
      Our patient was a 68-year-old Japanese woman. The results of endocrine testing
      after her first episode of non-convulsive status epilepticus suggested latent
      subclinical hypothyroidism: she had elevated thyroid-stimulating hormone with
      normal levels of free tri-iodothyronine and free thyroxine. On examination, a
      diagnosis of thyroid disorder was not supported by other test results and our
      patient remained untreated. A follow-up examination revealed that her thyroid
      stimulating hormone levels had spontaneously normalized. When she consulted
      another doctor for confusion, the transient increase in thyroid-stimulating
      hormone levels following non-convulsive status epilepticus was mistaken for
      subclinical hypothyroidism, and unfortunately treated with levothyroxine. Our
      patient then experienced levothyroxine-induced non-convulsive status epilepticus.
      CONCLUSIONS: In this report, we suggested possible mechanisms for latent
      hypothyroid-like hormone abnormality following epileptic seizures and the
      possibility of provoking epileptic seizures by administering levothyroxine for
      misdiagnosed subclinical hypothyroidism.

PMID- 21892966
TI  - Immunohistochemical comparison of CD5, lambda, and kappa expression in primary
      and recurrent buccal mucosa-associated lymphoid tissue (MALT) lymphomas.
AB  - Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of extranodal
      marginal zone B-cell lymphoma and is a distinct subtype of non-Hodgkin's
      lymphoma.Primary MALT lymphomas can also occur in the oral cavity, although their
      appearance in this location is rare. The neoplastic cells of which MALT lymphomas
      are composed express B-cell antigens and show monotypic immunoglobulin expression
      with light-chain restriction.Although neoplastic MALT lymphoma cells do not
      express CD5, previous studies have shown that CD5 positive MALT lymphomas are
      more prone to dissemination than those that do not express CD5. Moreover, there
      are some reports that describe kappa- and lambda- dual light chain expression in
      B cell malignant neoplasms.A 66-year-old Japanese woman with swelling of the
      right buccal mucosa was referred to our hospital. The lesion was excised and was
      pathologically diagnosed as a MALT lymphoma tumor with a t(11;18)(q21;q21)
      chromosome translocation.Swelling of the right buccal mucosa recurred 2 years
      later. The recurrent tumor was then excised and pathologically diagnosed as MALT
      lymphoma.Immunohistochemical examination of CD5, lambda, and kappa expressions
      revealed that the primary tumor was positive for CD5, kappa, and lambda, but the
      recurrent tumor was weakly positive for CD5 and kappa.With respect to lambda
      positivity, the recurrent tumor showed negativity.Our study suggests that
      immunohistochemical expression of CD5, kappa, and lambda in oral MALT lymphoma
      have the risk of recurrence.We first described the recurrence of CD5 positive
      MALT lymphoma in the oral cavity and compared the immunohistochemical expressions
      of CD5, lambda, and kappa between the primary and recurrent tumors.

PMID- 21892967
TI  - Associations of maternal pre-pregnancy obesity and excess pregnancy weight gains
      with adverse pregnancy outcomes and length of hospital stay.
AB  - BACKGROUND: It is relatively less known whether pre-pregnancy obesity and excess
      gestational weight gain (GWG) are associated with caesarean delivery, pregnancy
      complications, preterm birth, birth and placenta weights and increased length of
      postnatal hospital stay. METHODS: We used a population-based cohort of 6632 women
      who gave birth in Brisbane, Australia, between 1981 and 1983. The independent
      associations of pre-pregnancy obesity, GWG and institute of medicine (IOM)
      categories of combined pre-pregnancy BMI and GWG with outcomes were examined
      using multivariable regression (for continuous outcomes) and multivariable
      multinomial regression (for categorical outcomes) models. RESULTS: We found women
      who were obese prior to pregnancy and women who gained excess weight during
      pregnancy were at greater risk for a pregnancy complications (OR: 2.10; 1.74,
      2.54; age adjusted model), caesarean section (OR 1.29; 1.09, 1.54), higher birth
      weight difference (206.45 gm; 178.82, 234.08) and greater placental weight
      difference (41.16 gm; 33.83, 48.49) and longer length of hospital stay. We also
      found that mothers who gained inadequate weight or were underweight before
      pregnancy were at greater risk of preterm birth (2.27; 1.71, 3.00), lower risk of
      pregnancy complications (0.58; 0.44, 0.77) and had lower birth (-190.63;-221.05,
      160.20) and placental (-37.16; -45.23,-29.09) weights. Results indicate that all
      associations remain consistent after adjustment for a range of potential
      confounding factors with the exception of the association between pre-pregnancy
      obesity and hospital stay. CONCLUSIONS: Pre-pregnancy obesity or excessive GWG
      are associated with greater risk of pregnancy complications, caesarean delivery
      and greater birth and placenta weight. Excess GWG is associated with a longer
      stay in hospital after delivery, independent of pre-pregnancy BMI, pregnancy
      complications and caesarean delivery. In addition to pre-pregnancy obesity, it is
      vital that clinical practice considers excess GWG as another indicator of adverse
      pregnancy outcomes.

PMID- 21892968
TI  - Homology modeling of mosquito cytochrome P450 enzymes involved in pyrethroid
      metabolism: insights into differences in substrate selectivity.
AB  - BACKGROUND: Cytochrome P450 enzymes (P450s) have been implicated in insecticide
      resistance. Anopheles minumus mosquito P450 isoforms CYP6AA3 and CYP6P7 are
      capable of metabolizing pyrethroid insecticides, however CYP6P8 lacks activity
      against this class of compounds. FINDINGS: Homology models of the three An.
      minimus P450 enzymes were constructed using the multiple template alignment
      method. The predicted enzyme model structures were compared and used for
      molecular docking with insecticides and compared with results of in vitro
      enzymatic assays. The three model structures comprise common P450 folds but
      differences in geometry of their active-site cavities and substrate access
      channels are prominent. The CYP6AA3 model has a large active site allowing it to
      accommodate multiple conformations of pyrethroids. The predicted CYP6P7 active
      site is more constrained and less accessible to binding of pyrethroids. Moreover
      the predicted hydrophobic interface in the active-site cavities of CYP6AA3 and
      CYP6P7 may contribute to their substrate selectivity. The absence of CYP6P8
      activity toward pyrethroids appears to be due to its small substrate access
      channel and the presence of R114 and R216 that may prevent access of pyrethroids
      to the enzyme heme center. CONCLUSIONS: Differences in active site topologies
      among CYPAA3, CYP6P7, and CYP6P8 enzymes may impact substrate binding and
      selectivity. Information obtained using homology models has the potential to
      enhance the understanding of pyrethroid metabolism and detoxification mediated by
      P450 enzymes.

PMID- 21892969
TI  - Occult HCV or delayed viral clearance from lymphocytes of Chronic HCV genotype 3
      patients after interferon therapy.
AB  - BACKGROUND: A recently discovered occult HCV entity reported by various
      investigators seems to be highly controversial. Especially, the clinical
      significance of these findings remains uncertain. For optimal outcome of
      antiviral therapy, investigation of occult HCV needs a broad-based probe in order
      to investigate the results of viral therapy and its host/viral interaction. The
      current study was aimed at determining the prevalence of occult HCV in peripheral
      blood lymphocytes of predominantly genotype 3 HCV-infected patients after
      completion of antiviral therapy and to investigate long term outcomes in the
      presence or absence of PBMC positivity. METHOD: A total of 151 chronic, antiHCV
      and serum RNA-positive patients were enrolled in the study. Patients with a
      complete virological response at the end of treatment were screened for the
      presence of viral RNA in their PBMCs and were followed for up to one year for the
      presence of serum and PBMC viral genomic RNA. RESULTS: Out of 151 patients, 104
      (70%) responded to the prescribed interferon treatment and showed viral-clearance
      from serum. These were screened for the presence of genomic RNA in their PBMCs.
      Sixteen samples were PBMC-positive for viral RNA at the end of treatment (EOT).
      All these patients had also cleared the virus from peripheral blood cells after
      the 6-12 month follow-up study. CONCLUSION: True occult hepatitis C virus does
      not exist in our cohort. Residual viremia at the EOT stage merely reflects a
      difference in viral kinetics in various compartments that remains a target of
      immune response even after the end of antiviral therapy and is eventually cleared
      out at the sustained viral response (SVR).

PMID- 21892970
TI  - Targeting bone metastases starting from the preneoplastic niche: home sweet home.
AB  - The metastatic process is a multistep coordinated event with a high degree of
      efficiency. Specific subpopulations of cancer stem cells, with tumor-initiating
      and migratory capacity, can selectively migrate towards sites that are able to
      promote survival and/or proliferation of metastatic tumor cells through a
      microenvironment modification. Cross-talk between the bone microenvironment and
      cancer cells can facilitate bone tropism of cancer cells. Fully understanding
      this complexity represents a major challenge in anti-cancer research and a
      mandatory step towards the development of new drugs potentially able not only to
      reduce the consequences of bone lesions but also to target the metastatic process
      in visceral sites.

PMID- 21892971
TI  - 7th meeting of the Global Arthritis Research Network.
AB  - Last October, the 7th meeting of the Global Arthritis Research Network was held
      in Zurich, Switzerland. European and American experts who have made major recent
      contributions to molecular biology got together to provide insights into novel
      technologies and approaches useful for biomedical research, especially for
      research on arthritis and related conditions.

PMID- 21892972
TI  - Early versus late renal replacement therapy in acute kidney injury: the search
      for a definition of timing continues.

PMID- 21892973
TI  - In vivo and in vitro evidence for pleiotropic effects of levosimendan in the
      intensive care setting.
AB  - Levosimendan, in addition to its inotropic properties, could have anti
      inflammatory and anti-oxidative properties, and can potentially decrease the
      deleterious effects of reactive oxygen species on the tissues. In their study,
      Hasslacher and colleagues provided not only in vitro but also in vivo evidence
      that levosimendan could preserve organ function in acute heart failure and septic
      shock-induced myocardial depression via cooling down the oxidative burst of
      circulating cells.

PMID- 21892974
TI  - On the imperfect synchrony between patient and ventilator.
AB  - Because patient-ventilator asynchrony (PVA) is recognized as a major clinical
      problem for patients undergoing ventilatory assistance, automatic methods of PVA
      detection have been proposed in recent years. A novel approach is airflow
      spectral analysis, which, when related to visual inspection of airway pressure
      and flow waveforms, has been shown to reach a sensitivity and specificity of
      greater than 80% in detecting an asynchrony index of greater than 10%. The
      availability of automatic non-invasive methods of PVA detection at the bedside
      would likely be of benefit in intensive care unit practice, but they may be
      limited by shortcomings, so clear proof of their effectiveness is needed.

PMID- 21892975
TI  - Central venous oxygen saturation in septic shock--a marker of cardiac output,
      microvascular shunting and/or dysoxia?
AB  - Shock therapy aims at increasing central venous oxygen saturation (ScvO2), which
      is a marker of inadequate oxygen delivery. In this issue of Critical Care,
      Textoris and colleagues challenge this notion by reporting that high levels of
      ScvO2 are associated with mortality in patients with septic shock. This is of
      obvious interest, but as their retrospective design has inherent limitations, the
      association should be confirmed in a prospective, multicenter study with
      protocolized ScvO2 measurements and detailed registration of potentially
      confounding factors.

PMID- 21892976
TI  - Working with capacity limitations: operations management in critical care.
AB  - As your hospital's ICU director, you are approached by the hospital's
      administration to help solve ongoing problems with ICU bed availability. The ICU
      seems to be constantly full, and trauma patients in the emergency department
      sometimes wait up to 24 hours before receiving a bed. Additionally, the cardiac
      surgeons were forced to cancel several elective coronary-artery bypass graft
      cases because there was not a bed available for postoperative recovery. The
      hospital administrators ask whether you can decrease your ICU length of stay, and
      wonder whether they should expand the ICU to include more beds For help in
      understanding and optimizing your ICU's throughput, you seek out the operations
      management researchers at your university.

PMID- 21892978
TI  - Soluble CD40 ligand is not solely related to the presence and severity of sepsis.

PMID- 21892979
TI  - Are arterial blood gases necessary in the evaluation of acutely dyspneic
      patients?
AB  - Arterial blood gases (ABG) are obtained commonly in dyspneic persons presenting
      to emergency departments. The study by Burri and colleagues found that the
      information contained in ABG fails to distinguish between pulmonary and other
      causes of dyspnea. On the other hand, arterial pH was highly predictive of ICU
      admission and outcome. Until large clinical studies show equivalence between
      peripheral venous and ABG, we will continue to advocate the use of ABG in the
      evaluation of acute dyspnea.

PMID- 21892977
TI  - Bench-to-bedside review: Vasopressin in the management of septic shock.
AB  - This review of vasopressin in septic shock differs from previous reviews by
      providing more information on the physiology and pathophysiology of vasopressin
      and vasopressin receptors, particularly because of recent interest in more
      specific AVPR1a agonists and new information from the Vasopressin and Septic
      Shock Trial (VASST), a randomized trial of vasopressin versus norepinephrine in
      septic shock. Relevant literature regarding vasopressin and other AVPR1a agonists
      was reviewed and synthesized. Vasopressin, a key stress hormone in response to
      hypotension, stimulates a family of receptors: AVPR1a, AVPR1b, AVPR2, oxytocin
      receptors and purinergic receptors. Rationales for use of vasopressin in septic
      shock are as follows: first, a deficiency of vasopressin in septic shock; second,
      low-dose vasopressin infusion improves blood pressure, decreases requirements for
      norepinephrine and improves renal function; and third, a recent randomized,
      controlled, concealed trial of vasopressin versus norepinephrine (VASST) suggests
      low-dose vasopressin may decrease mortality of less severe septic shock. Previous
      clinical studies of vasopressin in septic shock were small or not controlled.
      There was no difference in 28-day mortality between vasopressin-treated versus
      norepinephrine-treated patients (35% versus 39%, respectively) in VASST. There
      was potential benefit in the prospectively defined stratum of patients with less
      severe septic shock (5 to 14 MUg/minute norepinephrine at randomization):
      vasopressin may have lowered mortality compared with norepinephrine (26% versus
      36%, respectively, P = 0.04 within stratum). The result was robust: vasopressin
      also decreased mortality (compared with norepinephrine) if less severe septic
      shock was defined by the lowest quartile of arterial lactate or by use of one
      (versus more than one) vasopressor at baseline. Other investigators found greater
      hemodynamic effects of higher dose of vasopressin (0.06 units/minute) but also
      unique adverse effects (elevated liver enzymes and serum bilirubin). Use of
      higher dose vasopressin requires further evaluation of efficacy and safety. There
      are very few studies of interactions of therapies in critical care--or septic
      shock--and effects on mortality. Therefore, the interaction of vasopressin
      infusion, corticosteroid treatment and mortality of septic shock was evaluated in
      VASST. Low-dose vasopressin infusion plus corticosteroids significantly decreased
      28-day mortality compared with corticosteroids plus norepinephrine (44% versus
      35%, respectively, P = 0.03; P = 0.008 interaction statistic). Prospective
      randomized controlled trials would be necessary to confirm this interesting
      interaction. In conclusion, low-dose vasopressin may be effective in patients who
      have less severe septic shock already receiving norepinephrine (such as patients
      with modest norepinephrine infusion (5 to 15 MUg/minute) or low serum lactate
      levels). The interaction of vasopressin infusion and corticosteroid treatment in
      septic shock requires further study.

PMID- 21892980
TI  - Effects of constant and changing temperature conditions on diapause induction in
      Helicoverpa armigera (Lepidoptera: Noctuidae).
AB  - The effects of photoperiod and temperature on the induction and termination of
      facultative pupal diapause in Helicoverpa armigera (Lepidoptera: Noctuidae) were
      investigated under laboratory conditions. Exposing H. armigera larvae to both
      constant and fluctuating temperature regimes with a mean of 25 degrees C and 20
      degrees C resulted in a type-III photoperiodic response curve of a short-long day
      insect. The long-day critical daylengths for diapause induction were ten hours
      and 12 hours at the constant temperatures of 25 degrees C and 20 degrees C,
      respectively. Higher incidences of diapause and higher values both for the longer
      and the shorter critical photoperiods for diapause induction were observed at
      fluctuating regimes compared with the corresponding constant ones. At alternating
      temperatures, the incidence of diapause ranged from 4.2% to 33.3% and was
      determined by the temperature amplitude of the thermoperiod and by the
      interaction of cryophase or thermophase with the photoperiod. Helicoverpa
      armigera larvae seem to respond to photoperiodic stimuli at temperatures >15
      degrees C and <30 degrees C; all insects entered diapause at a constant
      temperature of 15 degrees C, whereas none did so at a constant temperature of 30
      degrees C under all the photoperiodic regimes examined. Although chilling was not
      a prerequisite for diapause termination, exposure of diapausing pupae to chilling
      conditions significantly accelerated diapause development and the time of adult
      emergence. Therefore, temperature may be the primary factor controlling the
      termination of diapause in H. armigera.

PMID- 21892981
TI  - Laboratory rearing and life history of an emerging grape pest, Xylotrechus
      arvicola (Coleoptera: Cerambycidae).
AB  - Several aspects of the biology of Xylotrechus arvicola (Olivier), an emerging
      grape pest, were studied under laboratory conditions. Four diets were tested to
      rear this species in the laboratory. Among them, only one made rearing from larva
      to adult possible. The highest mortality, in all cases, was recorded during the
      first days of larval development. Larvae were kept 45 days at 8 degrees C to
      break diapause in order to reduce the normal field larval developmental time. The
      species' developmental time was similar between sexes, while pupal developmental
      time and weight were significantly greater for females than for males. As part of
      a complementary study, life table parameters of females obtained from the larvae
      reared on the artificial diet were compared to those of females emerged from
      field-infested grape root wood. Both laid the majority of eggs in the first two
      weeks after emergence, and they had a similar pre-laying period. Nevertheless,
      the females from the diet-reared larvae lived significantly longer, laid eggs
      over a longer period of time and showed higher fertility than those emerging from
      infested grape root, suggesting that diet fulfils larval nutritional needs. The
      species' laboratory-reared population exhibited a low intrinsic growth rate value
      (rm=0.01) as a result of its long egg-to-adult developmental time and its high
      larval mortality.

PMID- 21892982
TI  - The frequency of daily ethanol consumption influences the effect of ethanol on
      insulin sensitivity in rats fed a high-fat diet.
AB  - The different effects of ethanol on insulin sensitivity may be due to complex
      reasons. Here, we focus on the various daily ethanol consumption frequencies in
      rats fed a high-fat (HF) diet and explore the possible mechanism mediated by
      adiponectin and AMP-activated protein kinase (AMPK). A total of thirty-six male
      Wistar rats were fed a HF diet and were randomly divided into three groups: those
      that received tap water (C); those that received ethanol via a gastric tube twice
      per d (E1); those that received free access to ethanol for drinking (E2). The
      total daily ethanol dosage in groups E1 and E2 were the same (5 g/kg per d). At
      the end of 18 weeks, insulin sensitivity was evaluated. Adiponectin AMPK and
      GLUT4 levels were determined. We found that the different administration
      frequencies led to markedly different plasma ethanol concentrations and there
      were intimate relationships between plasma ethanol concentration and insulin
      sensitivity. Insulin resistance was markedly improved in group E1, whereas only a
      slight improvement was observed in group E2. Accordingly, adiponectin,
      phosphorylated AMPK and GLUT4 levels were significantly increased in group E1.
      Based on these findings, we propose that ethanol concentration might be the major
      influencing factor mediating the effect of ethanol on insulin sensitivity. At a
      total daily dosage of 5 g/kg per d, twice daily administration of ethanol was
      more beneficial than continuous drinking. The protective effect of ethanol might
      be mediated by increased adiponectin levels, which subsequently improve the
      activation of AMPKalpha and GLUT4 expression in adipose tissue.

PMID- 21892983
TI  - Late recurrence of infra-Hisian complete atrioventricular block.
AB  - Acquired complete atrioventricular block that is caused by infectious myocarditis
      is usually transient and has a favourable outcome. We report the case of a 15
      year-old girl who had complete infra-Hisian atrioventricular block due to adeno
      viral myocarditis and received a permanent pacemaker at the age of 10 months. The
      pacemaker lost its function at the age of 7 years. However, she experienced a
      late recurrence of complete atrioventricular block 10 years later. Complete
      atrioventricular block is rarely recovered if it persisted for 2 weeks. Even in
      the patients with late recovery, long-term follow-up and pacemaker therapy are
      still needed.

PMID- 21892984
TI  - A Bayesian approach for correcting for partial plating in fluctuation
      experiments.
AB  - The fluctuation experiment is the preferred method for estimating microbial
      mutation rates. A difficult task facing the data analyst is to infer the mean
      number of mutations from the number of mutant cells that only indirectly reflects
      the number of mutations. Partial plating, commonly practised in the laboratory,
      renders this task even more challenging by allowing only a portion of the mutant
      cells to be counted. In this paper, we propose a Bayesian approach to correcting
      for partial plating in the analysis of fluctuation experiments.

PMID- 21892985
TI  - Using automated extraction of hepatitis B tests for surveillance: evidence of
      decreasing incidence of acute hepatitis B in England.
AB  - Surveillance of acute hepatitis B in England is necessary to estimate incidence,
      determine routes of transmission and inform public health actions. Here we
      describe an automated process to extract information on testing for markers of
      hepatitis B infection in English sentinel laboratories between 2002 and 2008. The
      resulting data were used to identify individuals with acute infections, describe
      their characteristics and estimate the incidence of infection. Two-thirds of
      acute infections were in males. Heterosexual exposure and injecting drug use were
      the main risks reported. Annual incidence was estimated at 1.3/100 000 person
      years overall (1.7 and 0.6 for males and females, respectively) and declined each
      year. Automated extraction of hepatitis B markers, including quantitative results
      where available, can help to classify HBV status more accurately for
      surveillance. HBV incidence in England is at its lowest level in recent years.

PMID- 21892986
TI  - Serological evidence of Coxiella burnetii exposure in native marsupials and
      introduced animals in Queensland, Australia.
AB  - The state of Queensland has the highest incidence of Q fever in Australia. In
      recent years, there has been an increase in human cases where no contacts with
      the typical reservoir animals or occupations were reported. The aim of this study
      was to determine the seroprevalence of Coxiella burnetii in Australian native
      animals and introduced animals in northern and southeastern Queensland.
      Australian native marsupials sampled included the brushtail possum (Trichosurus
      vulpecula) and common northern bandicoot (Isoodon macrourus). Introduced species
      sampled included dingoes (Canis lupus dingo), cats (Felis catus), foxes (Vulpes
      vulpes) and pigs (Sus scrofa). Serum samples were tested by ELISA for both phase
      II and phase I antigens of the organism using an Australian isolate. The
      serological evidence of C. burnetii infection demonstrated in these species has
      public health implications due to their increasing movement into residential
      areas in regional Queensland. This study is the first known investigation of C.
      burnetii seroprevalence in these species in northern Queensland.

PMID- 21892988
TI  - Impaired visual scanning and memory for faces in high-functioning autism spectrum
      disorders: it's not just the eyes.
AB  - Prior studies suggest that autism spectrum disorders (ASD) are associated with a
      domain-specific memory impairment for faces. The underlying cause of this problem
      and its relation to impaired visual scanning of faces--particularly of the eyes-
      remains to be determined. We recorded eye movements while 22 high-functioning ASD
      and 21 typically developing (TD) adolescents encoded and later recognized faces
      and objects from a single, nonsocial object category (electric fans). Relative to
      TD subjects, ASD individuals had poorer memory for faces, but not fans.
      Correlational analyses showed significant relationships between recognition
      memory and fixations. Eye tracking during encoding revealed that TD subjects made
      more fixations to faces than fans, whereas ASD individuals did not differ in
      number of fixations made to each stimulus type. Moreover, although both the TD
      and ASD groups showed a strong preference for fixating the eyes more than the
      mouth, the ASD subjects were less likely than TD subjects to scan regions of the
      face outside of the primary facial features (i.e., eyes, nose, and mouth). We
      concluded that ASD individuals have a domain-specific memory impairment for faces
      relative to mechanical objects and that this impairment may be related to
      abnormal scanning during encoding.

PMID- 21892989
TI  - How to measure the onset of babbling reliably?
AB  - Various measures for identifying the onset of babbling have been proposed in the
      literature, but a formal definition of the exact procedure and a thorough
      validation of the sample size required for reliably establishing babbling onset
      is lacking. In this paper the reliability of five commonly used measures is
      assessed using a large longitudinal corpus of spontaneous speech from forty
      infants (age 0 ; 6-2 ; 0). In a first experiment it is shown that establishing
      the onset of babbling with reasonable (95%) confidence is impossible when the
      measures are computed only once, and when the number of vocalizations are not
      equal for all children at all ages. In addition, each measure requires a
      different minimal sample size. In the second experiment a robust procedure is
      proposed and formally defined that permits the identification of the onset of
      babbling with 95% confidence. The bootstrapping procedure involves extensive
      resampling and requires relatively few data.

PMID- 21892990
TI  - French immersion experience and reading skill development in at-risk readers.
AB  - We tracked the developmental influences of exposure to French on developing
      English phonological awareness, decoding and reading comprehension of English
      speaking at-risk readers from Grade 1 to Grade 3. Teacher-nominated at-risk
      readers were matched with not-at-risk readers in French immersion and English
      language programs. Exposure to spoken French phonetic and syllabic forms and to
      written French orthographic and morphological forms by children attending French
      immersion programs was expected to promote phonological, decoding and reading
      comprehension achievement. Growth in all outcomes was found, with children in
      immersion experiencing higher final status in phonological awareness and more
      rapid growth and higher final status in decoding, using multilevel modeling. At
      risk readers in French immersion experienced faster growth and higher final
      status in reading comprehension. Benefits to reading of exposure to an additional
      language are discussed in relation to cross-language transfer, phonological grain
      size and enhanced executive control processes.

PMID- 21892991
TI  - An examination of kernite (Na2B4O6(OH)2.3H2O) using X-ray and electron
      spectroscopies: quantitative microanalysis of a hydrated low-Z mineral.
AB  - Mineral borates, the primary industrial source of boron, are found in a large
      variety of compositions. One such source, kernite (Na2B4O6(OH)2.3H2O), offers an
      array of challenges for traditional electron-probe microanalysis (EPMA)-it is
      hygroscopic, an electrical insulator, composed entirely of light elements, and
      sensitive to both low pressures and the electron beam. However, the approximate
      stoichiometric composition of kernite can be analyzed with careful preparation,
      proper selection of reference materials, and attention to the details of
      quantification procedures, including correction for the time dependency of the
      sodium X-ray signal. Moreover, a reasonable estimation of the mineral's water
      content can also be made by comparing the measured oxygen to the calculated
      stoichiometric oxygen content. X-ray diffraction, variable-pressure electron
      imaging, and visual inspection elucidate the structural consequences of high
      vacuum treatment of kernite, while Auger electron spectroscopy and X-ray
      photoelectron spectroscopy confirm electron beam-driven migration of sodium and
      oxygen out of the near-surface region (sampling depth ~ 2 nm). These surface
      effects are insufficiently large to significantly affect the EPMA results
      (sampling depth ~ 400 nm at 5 keV).

PMID- 21892993
TI  - Quantitative energy dispersive X-ray analysis of submicrometric particles using a
      scanning electron microscope.
AB  - The quantitative scanning electron microscope-energy dispersive X-ray (SEM-EDX)
      analysis of a horneblende and two augite prismatic samples reduced to
      submicrometric particles was performed, and error due to the particle effects
      ("absent mass" and the "reduced absorption" effect) was minimized. Correction
      factors as a function of fragment size were obtained for O, Na, Mg, Si, Ca, and
      Fe. In addition, the influence of chemical composition of the samples used as
      standards (the matrix effect) on correction factors was evaluated. The results
      indicate that the absent mass effect is dominant for all elements except for the
      light elements O and Na, for which the reduced absorption effect is dominant. No
      significant matrix effect has been observed. By using corrected SEM-EDX data, the
      error on quantification of the element concentration has been estimated to be 3%
      relative for light elements and below 2% relative for heavy elements (notably,
      about 1% relative for Fe).

PMID- 21892995
TI  - Paving the way for transgenic schistosomes.
AB  - In parasitological research, significant progress has been made with respect to
      genomics and transcriptomics but transgenic systems for functional gene analyses
      are mainly restricted to the protozoan field. Gene insertion and knockout
      strategies can be applied to parasitic protozoa as well as gene silencing by RNA
      interference (RNAi). By contrast, research on parasitic helminthes still lags
      behind. Along with the major advances in genome and transcriptome analyses e.g.
      for schistosomes, methods for the functional characterization of genes of
      interest are still in their initial phase and have to be elaborated now, at the
      beginning of the post-genomic era. In this review we will summarize attempts made
      in the last decade regarding the establishment of protocols to transiently and
      stably transform or transfect schistosomes. Besides approaches using particle
      bombardment, electroporation or virus-based infection strategies to introduce DNA
      constructs into adult and larval schistosome stages to express reporter genes,
      first approaches have also been made in establishing protocols based on soaking,
      lipofection, and/or electroporation for RNA interference to silence gene
      activity. Although in these cases remarkable progress can be seen, the
      schistosome community eagerly awaits major breakthroughs especially with respect
      to stable transformation, but also for silencing or knock-down strategies for
      every schistosome gene of interest.

PMID- 21892997
TI  - [First trimester risk assessment].

PMID- 21892996
TI  - Multiple reassortment between pandemic (H1N1) 2009 and endemic influenza viruses
      in pigs, United States.
AB  - As a result of human-to-pig transmission, pandemic influenza A (H1N1) 2009 virus
      was detected in pigs soon after it emerged in humans. In the United States, this
      transmission was quickly followed by multiple reassortment between the pandemic
      virus and endemic swine viruses. Nine reassortant viruses representing 7
      genotypes were detected in commercial pig farms in the United States. Field
      observations suggested that the newly described reassortant viruses did not
      differ substantially from pandemic (H1N1) 2009 or endemic strains in their
      ability to cause disease. Comparable growth properties of reassortant and endemic
      viruses in vitro supported these observations; similarly, a representative
      reassortant virus replicated in ferrets to the same extent as did pandemic (H1N1)
      2009 and endemic swine virus. These novel reassortant viruses highlight the
      increasing complexity of influenza viruses within pig populations and the
      frequency at which viral diversification occurs in this ecologically important
      viral reservoir.

PMID- 21892998
TI  - [Misuse of antibiotics in swine production is a problem for Danish health care].

PMID- 21892999
TI  - [Increasing transmission of antibiotic resistance from animals to humans].
AB  - The importance of the animal reservoir for emergence of antimicrobial resistance
      in bacteria in humans is difficult to estimate. In this article we give our
      estimate of the importance and also highlight on which points we have become
      wiser during recent years. We conclude that it still is the human usage of
      antibiotics which contributes most to resistance observed in humans, but also
      that the contribution from animals is large and larger than estimated just a few
      years ago. This indicates the need to implement restriction on antimicrobial
      usage for both humans and animals.

PMID- 21893000
TI  - [Early post-operative mobilization and orthostatic intolerance].
AB  - Early mobilization after surgery is crucial for an enhanced recovery and can
      reduce complications associated with immobility. Symptoms such as nausea,
      vomiting, blurred vision and dizziness are however known to impede early
      mobilization. Together these symptoms comprise orthostatic intolerance (OI), in
      which the ultimate manifestation is syncope. In reference to find preventive and
      relevant treatment for OI studies with a multimodal approach have shown promising
      results, though the pathophysiology behind OI is not fully understood.

PMID- 21893001
TI  - [Methotrexate treatment of rheumatoid arthritis in Denmark].
AB  - In the recommended early, aggressive and continuous treatment strategy of
      rheumatoid arthritis (RA), methotrexate (MTX) is the anchor drug, and although
      generally well tolerated approximately 50% of the RA patients discontinue MTX
      treatment within five years. In a large Danish cohort study among newly diagnosed
      patients with RA only 21% had started MTX treatment within 90 days after referral
      to hospital and the median time-to-treatment initiation was 120 days.
      Furthermore, MTX compliance is considered generally high among Danish RA patients
      and the patients have strong beliefs about MTX necessity.

PMID- 21893002
TI  - [Coronary artery calcium score in cardiac CT increases the prognostic information
      of selected patients].
AB  - Cardiovascular disease is the leading cause of death in the western countries.
      Conventional risk evaluation of asymptomatic individuals is unfortunately
      inaccurate. There is a need for better diagnostic tools to identify persons, who
      will benefit from intensified preventive treatment. Coronary artery calcium score
      (CACS) measured by multi-slice CT scan contributes significantly to risk
      stratification especially in persons with intermediate risk assessed by
      conventional risk analysis. A CACS-guided preventive intervention strategy seems
      appealing to reduce mortality due to cardiovascular disease.

PMID- 21893003
TI  - [Radiotherapy in patients with a pacemaker or an implantable cardioverter
      defibrillator].
AB  - With an ageing population an increasing number of patients with a pacemaker or
      implantable cardioverter defibrillator will present at radiotherapy units due to
      malignancy. Two separate questionnaires concerning routines of departments
      treating this population were sent to Danish implanting cardiology centers and to
      radiotherapy departments. Differences in the handling of these patients were
      found. Removal of the devices and monitoring of the patients is assessed on a
      highly individual basis. In the absence of updated official guidelines,
      departments treating these patients should produce local instructions.

PMID- 21893004
TI  - [Mowat-Wilson syndrome: a report of three Danish cases].
AB  - Mowat-Wilson syndrome (MWS) is an autosomal dominant intellectual disability
      syndrome characterised by unique facial features and congenital anomalies such as
      Hirschsprung disease, congenital heart defects, corpus callosum agenesis and
      urinary tract anomalies. Some cases also present epilepsy, growth retardation and
      microcephaly. The syndrome is caused by mutations or deletions of the ZEB2 gene
      at chromosome 2q22-q23. MWS was first described in 1998 and until now
      approximately 180 cases have been reported worldwide. We report the first three
      molecularly confirmed Danish cases with MWS.

PMID- 21893005
TI  - [Successful treatment of diabetic gustatory hyperhidrosis with topical
      glycopyrrolate].
AB  - Gustatory hyperhidrosis is a condition characterised by excessive craniofacial
      sweating in relation to food intake and is associated with diabetic neuropathy.
      The existing guidelines for treatment of this condition include antiperspirants,
      oral anticholinergic treatment, ionophoresis, botulinum toxin injections and
      endothoracic surgery. In this case a patient with diabetes suffering from
      gustatory hyperhidrosis was treated successfully with topical glycopyrrolate, an
      anticholinergic agent applied directly on the affected area.

PMID- 21893006
TI  - [Congenital linear nevus sebaceus].
AB  - An unusual case of nevus sebaceous is described. Nevus sebaceous is a congenital
      epidermal hamartoma of the skin and the predilection site is the head or neck. In
      this case the nevus followed the lines of Blaschko along the back of the left
      lower extremity. The linear lesion seemed papulovesicular which caused suspicion
      of incontinentia pigmenti or infection, and the boy received antimicrobial
      treatment until a biopsy revealed the correct diagnosis. We wish to emphasize
      this clinical picture to spare the patient and relatives from unnecessary tests,
      treatment and concern.

PMID- 21893007
TI  - [Surgical treatment of neurocysticercosis in a 12-year old child].
AB  - We present a case of neurocysticercosis in a 12-year old refugee from Zambia.
      Magnetic resonance imaging demonstrated a solitary, ring enhancing cystic lesion
      located subcortically in the left parietal lobe. Despite extensive diagnostic
      workup it was not possible to rule out alternative differential diagnoses.
      Serological tests for neurocysticercosis came out negative. The lesion was
      removed en bloc using microsurgical technique. Subsequent histological
      examination revealed a thick-walled cyst containing a cysticercus identifiable as
      a Taenia solium.

PMID- 21893009
TI  - Gender bias in specialty preferences among Danish medical students: a cross
      sectional study.
AB  - INTRODUCTION: Female medical students tend to prefer person-oriented specialties
      characterized by close doctor-patient contact and aspects of care. Conversely,
      male medical students tend to seek towards specialties with elements of autonomy,
      technology and "action" . Furthermore, female doctors will outnumber male doctors
      in Denmark by 2017 and this may have implications for the availability of
      specialized doctors. MATERIAL AND METHODS: Data derives from a baseline
      questionnaire pertaining to a Danish follow-up study. A total of 561 first year
      medical students enrolled in 2006 and 2007 answered the questionnaire. Binary
      logistic regression analysis was used to calculate odds ratio estimates of the
      relationship between gender and specialty preference. Variables measuring self
      image were included in the analysis as potential mediators. RESULTS: 47% female
      and 19% male students pursued personoriented specialties and 46% female and 68%
      male students pursued technique-oriented specialties. More female students
      pursued technique-oriented specialties than in 1992. Female students have 69%
      less probability of choosing a technique-oriented specialty than males. This
      association is mediated by lack of self-confidence. CONCLUSION: If specialty
      preferences are persistent during medical school, the results suggest that we
      will face more difficulties recruiting males to person-oriented specialties than
      females to technique-oriented specialties in the future. Furthermore, when
      addressing students' specialty preferences, we should consider both self
      confidence and gender. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 21893008
TI  - Paediatric outcomes following intrauterine exposure to serotonin reuptake
      inhibitors: a systematic review.
AB  - The use of serotonine reuptake inhibitors (SRIs) is increasing among Danish
      pregnant women. This systematic review addresses the potential adverse effects on
      the foetus and child of maternal SRI medication. The literature indicates a
      slightly increased risk of cardiovascular malformations and persistent pulmonary
      hypertension of the new-born, while evidence regarding the risk of preterm
      labour, low birth weight, low Apgar score, prolonged QT interval and miscarriage
      is less clear. An estimated 20-30% of infants will have neonatal symptoms
      following intrauterine SRI exposure. The symptoms may be caused by SRI
      withdrawal, toxicity or their overlap, but symptom aetiology basically remains
      controversial. The infants may exhibit neurological, gastrointestinal, autonomic,
      endocrine or respiratory symptoms. Although the symptoms are self-limited, the
      families may be seriously affected. In general, studies do not address this
      important aspect. Evidence concerning long-term effects is surprisingly sparse
      and many studies have important methodological limitations. However, present
      evidence does not convincingly indicate detrimental long-term effects. Until
      sufficient safety studies have been carried out, SRI must be used with caution in
      pregnancy and every treatment of the pregnant woman should be thoroughly
      considered.

PMID- 21893010
TI  - Video electroencephalography monitoring differentiates between epileptic and non
      epileptic seizures.
AB  - INTRODUCTION: Epilepsy is often misdiagnosed and approximately one in every four
      patients diagnosed with refractory epilepsy does not have epilepsy, but instead
      non-epileptic seizures. Video electroencephalography monitoring (VEM) is the gold
      standard for differentiation between epileptic and non-epileptic seizures. The
      purpose of this study was to investigate the effectiveness of VEM as a diagnostic
      tool. MATERIAL AND METHODS: In this retrospective study, we have investigated the
      diagnostic outcome of 155 in patients undergoing VEM at Copenhagen University
      Hospital (Rigshospitalet) over a two-year period. RESULTS: The study showed that
      VEM revealed a diagnosis in 80%. Epilepsy was diagnosed in 38% and epilepsy was
      rejected in 43% of cases. In the remaining 20% of cases, epilepsy could not be
      excluded. Among patients who were referred in antiepileptic drug treatment, 29%
      did not have epilepsy. The highest diagnostic yield was obtained when patients
      had seizures with ictal electroencephalography paroxysms during VEM. CONCLUSION:
      Several patients without epilepsy are treated as if they had epilepsy. VEM is a
      costly method, but with a large diagnostic yield and should therefore be used
      when there is doubt about the diagnosis in patients with relatively frequent
      seizures. The use of VEM is expedient to make the correct diagnosis, optimize
      medical treatment of patients with epilepsy and to avoid unnecessary treatment in
      patients without epilepsy. FUNDING: not relevant. TRIAL REGISTRATION: not
      relevant.

PMID- 21893011
TI  - Many unexpected abdominal findings on staging computed tomography in patients
      with colorectal cancer.
AB  - INTRODUCTION: Computed tomography (CT) was proven to be superior to preoperative
      abdominal ultrasound in the preoperative setting for detection of hepatic
      metastases from colorectal cancer (CRC). The higher sensitivity of CT has
      resulted in a number of unexpected abdominal findings of varying importance; an
      issue that was previously studied in relation to CT colonography, but not in
      relation to staging CT with intravenous contrast in CRC patients. The aim of the
      present study was to evaluate the number and significance of such unexpected
      findings on staging CTs in CRC patients. MATERIAL AND METHODS: The study
      comprises a retrospective analysis of 247 consecutive patients who underwent
      colorectal cancer surgery at Roskilde Hospital, Denmark, in 2009. A preoperative
      abdominal staging CT was performed in 245 of these patients. All CT scans and
      patient records were reviewed by the authors. The unexpected CT findings were
      classified as being of high, moderate or low clinical importance according to
      whether they required treatment relatively promptly, later or did not require
      treatment at all, respectively. RESULTS: Overall, 114 patients (47%) had
      unexpected findings. Nineteen of the 137 findings (14%) or 8% in all patients
      were considered to be of high importance. Three per cent of all patients had
      abdominal aortic aneurysms, 2% had CRC metastases to the adrenal glands, 2%
      primary kidney tumours and 1% gynaecologic tumours. Twenty per cent of the
      patients had findings of moderate importance and 29% findings of low importance.
      CONCLUSION: Staging CT in CRC patients showed nearly 8% of unexpected abdominal
      findings of high clinical importance requiring relatively prompt treatment.
      FUNDING: not relevant. TRIAL REGISTRATION: not relevant.

PMID- 21893012
TI  - High maternal HbA1c is associated with overweight in neonates.
AB  - INTRODUCTION: The aims of this study were to determine the prevalence of women
      with gestational diabetes mellitus (GDM) not obtaining HbA1c within the normal
      range (<= 5.6%) before delivery and to examine whether elevated HbA1c values are
      associated with an increased risk of large for gestational age (LGA) infants.
      MATERIAL AND METHODS: A population of 148 women with singleton pregnancies who
      had been diagnosed with GDM < 34 weeks, and who had a minimum of two HbA1c tests
      with a >= 3 week interval. They were divided into those obtaining a HbA1c <=
      5.6%, and those who did not before delivery and further stratified according to
      baseline HbA1c <= or > 5.6%. The primary outcome was LGA infants. RESULTS: A
      total of 51 (34%) women did not obtain a HbA1c <= 5.6% before delivery. The
      median HbA1c before delivery was 5.9% versus 5.3% in the two groups. At baseline,
      body mass index and HbA1c were higher in the women not obtaining the goal (30.9
      versus 27.8 kg/m2, 5.9% versus 5.1%, both p < 0.01). Women with an elevated HbA1c
      before delivery had a higher prevalence of LGA infants (adjusted odds ratio (OR)
      3.1 (95% confidence interval (CI) 1.3-7.6) and neonatal hypoglycaemia (adjusted
      OR 6.2 (95% CI 1.3-29.0). Other pregnancy outcomes were similar in the two
      groups. Stratification according to baseline HbA1c did not seem to change the
      result. CONCLUSION: Women with GDM not obtaining HbA1c within the normal range
      before delivery had a threefold increased risk of having an LGA infant and a
      sixfold increased risk of neonatal hypoglycaemia. FUNDING: not relevant. TRIAL
      REGISTRATION: not relevant.

PMID- 21893013
TI  - Use of preoperative bowel preparation in elective colorectal surgery in Denmark
      remains high.
AB  - INTRODUCTION: Previous studies have shown that preoperative bowel preparation
      does not influence the frequency of postoperative complications after elective
      open colonic resections. The Danish Colorectal Cancer Group (DCCG) recommends
      that mechanical bowel preparation (MBP) should be omitted prior to elective
      colonic resections. Several surveys show that most surgeons use MBP before
      colorectal surgery. The aim of this survey was to investigate the use of
      preoperative bowel preparation in elective colonic and rectal resections in
      Denmark. MATERIAL AND METHODS: The survey was conducted in 2009. A questionnaire
      on the use of preoperative bowel preparation in elective colonic and rectal
      resections performed in 2008 was sent to all the departments of surgery that
      perform colorectal surgery in Denmark. RESULTS: 34% of the patients received
      bowel preparation before open colonic resection compared with 81% before open
      rectal resection. Overall, the frequency of bowel preparation was significantly
      higher in laparoscopic (63%) than in open surgery (50%). CONCLUSION: MBP before
      elective open colonic resections remains widely used despite the national DCCG
      guideline. MBP before laparoscopic colorectal resections was more frequently used
      than before open colorectal resections as MBP before rectal resections was more
      frequently used than before colonic resections. The need for preoperative bowel
      preparation in these procedures has yet to be determined. FUNDING: not relevant.
      TRIAL REGISTRATION: not relevant.

PMID- 21893014
TI  - Evidence based evaluation of immuno-coagulatory interventions in critical care.
AB  - Cochrane systematic reviews with meta-analyses of randomised trials provide
      guidance for clinical practice and health-care decision-making. In case of
      disagreements between research evidence and clinical practice, high quality
      systematic reviews can facilitate implementation or deimplementation of medical
      interventions into clinical practice. This applies especially to treatment of
      critically ill patients where interventions are most often costly and the
      clinical conditions are associated with high mortality. OBJECTIVES: To assess the
      potential benefits or harms of 1) antithrombin III (AT III) for critically ill
      patients; 2) inhaled nitric oxide (INO) for acute respiratory distress syndrome
      (ARDS) and acute lung injury (ALI); 3) aerosolized prostacyclin for ARDS and ALI;
      4) thrombelastography (TEG) or thromboelastometry (ROTEM) to monitor haemotherapy
      versus usual care in patients with massive transfusion. METHODS: We performed
      four systematic reviews of relevant randomised clinical trials. To quantify the
      estimated effect of various interventions, we conducted meta-analyses, where
      appropriate, to determine intervention effects using the Cochrane Collaboration
      methodology, trial sequential analyses (TSA), the GRADE, and the PRISMA
      guidelines when conducting our systematic reviews. All reviews were performed
      according to published protocols following the recommendations of the Cochrane
      Handbook for systematic reviews of interventions. We performed multiple subgroup
      and sensitivity analyses with regard to methodological quality and various
      clinical outcomes. Trials were identified through Cochrane Central Register of
      Controlled Trials (CENTRAL), MEDLINE, EMBASE Science Citation Index-Expanded, The
      Chinese Biomedical Database and LILACS. We included all randomized clinical
      trials. We hand-searched reference lists, reviews, and contacted authors and
      experts for additional trials. We searched ClinicalTrials.gov, Centre Watch
      Clinical Trials Listing Service and ControlledTrials.com for missed, unreported,
      or ongoing trials. We screened bibliographies of relevant articles and conference
      proceedings and wrote to trialists and pharmaceutical companies producing the
      drugs in question. RESULTS: Four systematic reviews included a total of 44 trials
      with 5,551 patients. Only 15 of the trials were classified as trials with low
      risk of bias (high methodological quality) regarding generation of the allocation
      sequence, allocation concealment, blinding, follow-up and other types of bias. 1)
      Compared with placebo or no intervention, AT III did not significantly affect
      overall mortality (relative risk (RR) 0.96, 95% confidence interval (CI) 0.89 to
      1.03). No subgroup analyses on risk of bias, populations of patients, or with and
      without adjuvant heparin yielded significant results. AT III significantly
      increased the risk of bleeding events (RR 1.52, 95% CI 1.30 to 1.78). 2) INO
      showed no statistically significant effect on overall mortality (RR 1.06, 95% CI
      0.93 to 1.22) and in several subgroup and sensitivity analyses, indicating robust
      results. Limited data demonstrated no effect of INO on duration of ventilation,
      ventilator-free days, and length of stay in the intensive care unit and hospital.
      We found a statistically significant, but transient improvement in oxygenation in
      the first 24 hours, expressed as the ratio of PO2 to fraction of inspired oxygen
      (mean difference (MD) 15.91, 95% CI 8.25 to 23.56). However, INO appears to
      significantly increase the risk of renal impairment among adults (RR 1.59, 95% CI
      1.17 to 2.16) but did not significantly affect the risk of bleeding or
      methaemoglobin or nitrogen dioxide formation. 3) We found only one small low risk
      of bias paediatric trial examining the role of aerosolized prostacyclin in ALI or
      ARDS. Based on this limited amount of data, we were unable to support or refute
      the routine use of this intervention in ALI or ARDS. 4) Compared with standard
      treatment, TEG or ROTEM showed no statistically significant effect on overall
      mortality (RR 0.77, 95% CI 0.35 to 1.72) but only five trials provided data on
      mortality. Our analyses demonstrated a statistically significant effect of TEG or
      ROTEM on the amount of bleeding (MD -85.05 ml, 95% CI -140.68 to -29.42) but
      failed to show any statistically significant effect on other predefined outcomes.
      However, whether this reduction has implication for the patient's clinical
      condition is still uncertain. CONCLUSION: We did not find reliable evidence to
      support the clinical use of the assessed immuno-coagulatory interventions for
      general use in critical care based on the available evidence. A large proportion
      of the trials had serious methodological shortcomings, small number of patients,
      and short trial duration. The sparse data provided in the included trials may be
      or may not be promising but is not necessarily evidence of absence of a
      beneficial or harmful effect, because many of the outcome measures have not been
      adequately addressed so far. There is an urgent need for several randomised
      clinical trials with low risk of bias and low risk of random error to evaluate
      the use of the assessed interventions.

PMID- 21893015
TI  - The influence of parathyroid hormone treatment on implant fixation.
AB  - INTRODUCTION: Primary joint replacements generally function well with excellent
      clinical results. However, failure rates for young patients are still high and
      increasing in number. The longterm survival of an uncemented prosthesis is
      influenced by multiple factors depending on host physiology as well as properties
      of implanted material, initial mechanical stability, early osseointegration, and
      the surrounding bone. Parathyroid hormone is the principal regulator of calcium
      homeostasis and involved in the control of bone remodelling. Parathyroid hormone
      administered intermittently increases bone formation and mass by osteoblast
      stimulation. Early osseointegration and implant fixation could potentially be
      enhanced with adjuvant parathyroid hormone treatment. The aim of the studies in
      this PhD thesis was to determine if implant fixation of experimental implants can
      be improved with adjuvant intermittent administration of parathyroid hormone.
      STUDIES: All studies used an experimental canine model of early implant fixation
      inserting porous coated titanium alloy implants with no weight bearing in a bed
      of cancellous bone. The study design was un-paired. Test animals were randomised
      to PTH (1-34) 5 MUm/kg daily for 4 weeks. Implant fixation was defined by
      mechanical stability and osseointegration. Study I investigated the effect of
      parathyroid hormone on implant fixation of implants inserted press fit with
      surrounding bone in the proximal tibia of 20 canines. Histomorphometric analysis
      showed increased amount of new bone in contact with the implant. No improvement
      was observed in the surrounding bone. PTH did not increase mechanical fixation in
      pushout test. Study II investigated the effect of parathyroid hormone on implant
      fixation of implants surrounded by a critical 1 mm gap. Implants where inserted
      in the tibia of 20 canines. Bone density was increased in the inner gap and outer
      gap with PTH treatment. Bone at implant interface improved with PTH but did not
      achieve significance. Push-out testing showed that PTH Increased mechanical
      implant fixation in shear stiffness and total energy absorption. Shear strength
      was not significantly increased. Study III investigated the effect on implant
      fixation of implants surrounded by a 2.5 mm gap in which morsellised allograft
      was impacted. Implants were inserted in 20 Canines in the humerus.
      Histomorphometric analysis showed that PTH increased the amount of new bone
      within the gap, but not in contact the implant. There were no differences in
      amount of allograft. The push-out testing showed no differences in mechanical
      parameters. CONCLUSION: The studies in this PhD thesis demonstrated that
      parathyroid hormone increases bone healing around implants in situations of
      insertion in press-fit or in more challenging environments of empty and grafted
      gaps. Early fixation was increased in implants with gaps, in which pure gap bone
      stimulation improved fixation. This warrants further preclinical studies.

PMID- 21893016
TI  - Characterization of Trypanosoma cruzi telomerase.
AB  - High telomerase activity is always associated with actively dividing cells,
      however the detection of this activity in dividing Leishmania and Trypanosoma
      cruzi cells has always been disappointingly low. Recently, we have found that
      Leishmania major telomerase activity can be activated by heat, which combined
      with dilutions of the nuclear extracts produced an increase in activity
      comparable to cancer cells. Here we examined whether T. cruzi telomerase shares
      the same physicochemical properties of primer specificity and overall features of
      the L. major. Our studies revealed that no telomerase inhibitory factors were
      present in the nuclear lysates of T. cruzi however the enzyme was activated by
      heat and was very resilient to heat denaturation. We also showed the extension
      primer specificity, susceptibility to RNase-A and RNase-H digestion, and the
      effect of telomerase inhibitors.

PMID- 21893017
TI  - Pathological alteration of FoxO3a activity promotes idiopathic pulmonary fibrosis
      fibroblast proliferation on type i collagen matrix.
AB  - Idiopathic pulmonary fibrosis (IPF) is a prevalent, progressive, and incurable
      fibroproliferative lung disease. The phenotype of IPF fibroblasts is
      characterized by their ability to elude the proliferation-suppressive properties
      of polymerized type I collagen. The mechanism underlying this pathological
      response is incompletely understood but involves aberrant activation of the
      phosphatidylinositol 3-kinase-Akt signaling pathway owing to inappropriately low
      phosphatase and tensin homolog phosphatase activity. Akt can phosphorylate and
      inactivate the forkhead box O3a (FoxO3a) transcriptional factor, which, when
      transcriptionally active, increases the expression of the CDK inhibitor p27 and
      promotes cell cycle arrest. Herein, we demonstrate that IPF fibroblasts display
      high levels of inactive FoxO3a compared with nonfibrotic control fibroblasts
      because of their high Akt activity. We found that p27 levels are decreased in IPF
      compared with control fibroblasts cultured on polymerized collagen. Furthermore,
      overexpression of FoxO3a in IPF fibroblasts increases p27 levels and suppresses
      the ability of IPF fibroblasts to proliferate on polymerized collagen. In
      contrast, the expression of dominant-negative FoxO3a augmented control fibroblast
      proliferation. IHC examination of fibroblastic foci in IPF lung tissue
      demonstrates the presence of inactive FoxO3a in cells within fibroblastic foci.
      These data indicate that the ability of IPF fibroblasts to circumvent the
      proliferation-suppressive properties of polymerized collagen involves
      inactivation of FoxO3a by high Akt activity, resulting in down-regulation of p27.

PMID- 21893018
TI  - Acid sphingomyelinase gene deficiency ameliorates the hyperhomocysteinemia
      induced glomerular injury in mice.
AB  - Hyperhomocysteinemia (hHcys) enhances ceramide production, leading to the
      activation of NADPH oxidase and consequent glomerular oxidative stress and
      sclerosis. The present study was performed to determine whether acid
      sphingomyelinase (Asm), a ceramide-producing enzyme, is implicated in the
      development of hHcys-induced glomerular oxidative stress and injury.
      Uninephrectomized Asm-knockout (Asm(-/-)) and wild-type (Asm(+/+)) mice, with or
      without Asm short hairpin RNA (shRNA) transfection, were fed a folate-free (FF)
      diet for 8 weeks, which significantly elevated the plasma Hcys level compared
      with mice fed normal chow. By using in vivo molecular imaging, we found that
      transfected shRNAs were expressed in the renal cortex starting on day 3 and
      continued for 24 days. The FF diet significantly increased renal ceramide
      production, Asm mRNA and activity, urinary total protein and albumin excretion,
      glomerular damage index, and NADPH-dependent superoxide production in the renal
      cortex from Asm(+/+) mice compared with that from Asm(-/-) or Asm shRNA
      transfected wild-type mice. Immunofluorescence analysis showed that the FF diet
      decreased the expression of podocin but increased desmin and ceramide levels in
      glomeruli from Asm(+/+) mice but not in those from Asm(-/-) and Asm shRNA
      transfected wild-type mice. In conclusion, our observations reveal that Asm plays
      a pivotal role in mediating podocyte injury and glomerular sclerosis associated
      with NADPH oxidase-associated local oxidative stress during hHcys.

PMID- 21893019
TI  - Pathophysiological mechanisms of autosomal dominant congenital stromal corneal
      dystrophy: C-terminal-truncated decorin results in abnormal matrix assembly and
      altered expression of small leucine-rich proteoglycans.
AB  - Autosomal-dominant congenital stromal corneal dystrophy (CSCD) is a human genetic
      disease characterized by corneal opacities beginning shortly after birth. It is
      linked to a frameshift mutation in decorin, resulting in a C-terminal truncation
      lacking 33 amino acids that includes the "ear" repeat, a feature specific for
      small leucine-rich proteoglycans. Our goals are to elucidate the roles of the
      mutant decorin in CSCD pathophysiology and to decipher the mechanism whereby
      mutant decorin affects matrix assembly. A novel animal model that recapitulates
      human CSCD was generated. This transgenic mouse model targets expression of
      truncated decorin to keratocytes, thereby mimicking the human frameshift
      mutation. Mutant mice expressed both wild-type and mutant decorin. Corneal
      opacities were found throughout, with increased severity toward the posterior
      stroma. The architecture of the lamellae was disrupted with relatively normal
      lamellae separated by regions of abnormal fibril organization. Within abnormal
      zones, the interfibrillar spacing and the fibril diameters were increased.
      Truncated decorin negatively affected the expression of endogenous decorin,
      biglycan, lumican, and keratocan and positively affected fibromodulin. Our
      results provide a mechanistic explanation for the generation of corneal opacities
      in CSCD. Thus, truncated decorin acts in a dominant-negative manner to interfere
      dually with matrix assembly and binding to receptor tyrosine kinases, thereby
      causing abnormal expression of endogenous small leucine-rich proteoglycans
      leading to structural abnormalities within the cornea and vision loss.

PMID- 21893020
TI  - miR-193b Regulates Mcl-1 in Melanoma.
AB  - MicroRNAs play important roles in gene regulation, and their expression is
      frequently dysregulated in cancer cells. In a previous study, we reported that
      miR-193b represses cell proliferation and regulates cyclin D1 in melanoma cells,
      suggesting that miR-193b could act as a tumor suppressor. Herein, we demonstrate
      that miR-193b also down-regulates myeloid cell leukemia sequence 1 (Mcl-1) in
      melanoma cells. MicroRNA microarray profiling revealed that miR-193b is expressed
      at a significantly lower level in malignant melanoma than in benign nevi.
      Consistent with this, Mcl-1 is detected at a higher level in malignant melanoma
      than in benign nevi. In a survey of melanoma samples, the level of Mcl-1 is
      inversely correlated with the level of miR-193b. Overexpression of miR-193b in
      melanoma cells represses Mcl-1 expression. Previous studies showed that Mcl-1
      knockdown cells are hypersensitive to ABT-737, a small-molecule inhibitor of Bcl
      2, Bcl-X(L), and Bcl-w. Similarly, overexpression of miR-193b restores ABT-737
      sensitivity to ABT-737-resistant cells. Furthermore, the effect of miR-193b on
      the expression of Mcl-1 seems to be mediated by direct interaction between miR
      193b and seed and seedless pairing sequences in the 3' untranslated region of Mcl
      1 mRNA. Thus, this study provides evidence that miR-193b directly regulates Mcl-1
      and that down-regulation of miR-193b in vivo could be an early event in melanoma
      progression.

PMID- 21893022
TI  - Whole cell microtubule analysis by flow cytometry.
AB  - Perturbation of the tubulin/microtubule dynamic in cells is perhaps the single
      most important mode of action of anticancer drugs. Standard methods for
      identifying and evaluating compounds for their ability to alter tubulin
      polymerization are low throughput, labor intensive, expensive, or make their
      assessment in vitro. Here we report a method to rapidly quantify the extent of
      tubulin polymerization in whole cells using flow cytometry, and we use this
      technique to evaluate compounds that stabilize and destabilize microtubule
      formation. This facile method is useful for conveniently, quantitatively, and
      cost-effectively comparing small molecules that perturb tubulin polymerization.

PMID- 21893021
TI  - mdx(5cv) mice manifest more severe muscle dysfunction and diaphragm force
      deficits than do mdx Mice.
AB  - Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle
      dysfunction leading to premature death by the third decade of life. The mdx
      mouse, the most widely used animal model of DMD, has been extremely useful to
      study disease mechanisms and to screen new therapeutics. However, unlike patients
      with DMD, mdx mice have a very mild motor function deficit, posing significant
      limitations for its use as a platform to assess the impact of treatments on motor
      function. It has been suggested that an mdx variant, the mdx(5cv) mouse, might be
      more severely affected. Here, we compared the motor activity, histopathology, and
      individual muscle force measurements of mdx and mdx(5cv) mice. Our study revealed
      that mdx(5cv) mice showed more severe exercise-induced fatigue, Rotarod
      performance deficits, and gait anomalies than mdx mice and that these deficits
      began at a younger age. Muscle force studies showed more severe strength deficits
      in the diaphragm of mdx(5cv) mice compared to mdx mice, but similar force
      generation in the extensor digitorum longus. Muscle histology was similar between
      the two strains. Differences in genetic background (genetic modifiers) probably
      account for these functional differences between mdx strains. Overall, our
      findings indicate that the mdx and mdx(5cv) mouse models of DMD are not
      interchangeable and identify the mdx(5cv) mouse as a valuable platform for
      preclinical studies that require assessment of muscle function in live animals.

PMID- 21893023
TI  - Pluripotentialities of a quenched fluorescent peptide substrate library:
      enzymatic detection, characterization, and isoenzymes differentiation.
AB  - Protease inhibitors represent a major class of drugs, even though a large number
      of proteases remain unexplored. Consequently, a great interest lies in the
      identification of highly sensitive substrates useful for both the
      characterization and the validation of these enzyme targets and for the design of
      inhibitors as potential therapeutic agents through high-throughput screening
      (HTS). With this aim, a synthetic substrate library, in which the highly
      fluorescent (L)-pyrenylalanine residue (Pya) is efficiently quenched by its
      proximity with the p-nitro-(L)-phenylalanine (Nop) moiety, was designed. The
      cleavage between Pya and Nop leads to a highly fluorescent metabolite providing
      the required sensitivity. This library, characterized by a water-soluble primary
      sequence Ac-SGK-Pya-(X)(n)(-)Nop-GGK-NH(2), X being a mixture of 10 natural amino
      acids (A, I, L, K, F, W, E, Q, T, P) and n varying from 0 to 3, was validated
      using enzymes belonging to the four main types of hydrolases: serine-, metallo-,
      cystein-, and aspartyl-proteases. The selectivity of substrates belonging to this
      library was evidenced by characterizing specific substrates for the isoenzymes
      NEP-1 and NEP-2. This library easily synthesized is of great interest for the
      identification and development of selective and specific substrates for still
      uncharacterized endoproteases.

PMID- 21893024
TI  - Role of proximal methionine residues in Leishmania major peroxidase.
AB  - The active site architecture of Leishmania major peroxidase (LmP) is very similar
      with both cytochrome c peroxidase and ascorbate peroxidase. We utilized point
      mutagenesis to investigate if the conserved proximal methionine residues (Met248
      and Met249) in LmP help in controlling catalysis. Steady-state kinetics of
      methionine mutants shows that ferrocytochrome c oxidation is <2% of wild type
      levels without affecting the second order rate constant of first phase of
      Compound I formation, while the activity toward a small molecule substrate,
      guaiacol or iodide, increases. Our diode array stopped-flow spectral studies show
      that the porphyrin pi-cation radical of Compound I in mutant LmP is more stable
      than wild type enzyme. These results suggest that the electronegative sulfur
      atoms of the proximal pocket are critical factors for controlling the location of
      a stable Compound I radical in heme peroxidases and are important in the
      oxidation of ferrocytochrome c.

PMID- 21893025
TI  - Competing interactions for antimicrobial selectivity based on charge
      complementarity.
AB  - Antimicrobial peptides (AMPs) are an evolutionary conserved component of the
      innate immune system and possible templates for the development of new
      antibiotics. An important property of antimicrobial peptides is their ability to
      discriminate bacterial from eucaryotic cells which is attributed to the
      difference in lipid composition of the outer leaflet of the plasma membrane
      between the two types of cells. Whereas eucaryotic cells usually expose
      zwitterionic lipids, procaryotic cells expose also anionic lipids which bind the
      cationic antimicrobial peptides electrostatically. An example is the
      antimicrobial peptide NK-2 which is highly cationic and favors binding to anionic
      membranes. In the present study, the difference in binding affinity of NK-2 for
      palmitoyl-oleoyl-phosphatidyl-glycerol (POPG) and palmitoyl-oleoyl-phosphatidyl
      choline (POPC) is studied using molecular dynamics simulations in conjunction
      with a coarse grained model and thermodynamic integration, by computing the
      change in free energy and its components upon the transfer of NK-2 from POPC to
      POPG. The transfer is indeed found to be highly favorable. Interestingly, the
      favorable contribution from the electrostatic interaction between the peptide and
      the anionic lipids is overcompensated by an unfavorable contribution from the
      change in lipid-cation interactions due to the release of counterions from the
      lipids. The increase in entropy due to the release of the cations is compensated
      by other entropic components. The largest favorable contribution arises from the
      solvation of the counterions. Overall the interaction between NK-2 and POPG is
      not determined by a single driving force but a subtle balance of competing
      interactions.

PMID- 21893026
TI  - Membrane properties of and cholesterol's interactions with a biologically
      relevant three-chain sphingomyelin: 3O-palmitoyl-N-palmitoyl-D-erythro
      sphingomyelin.
AB  - Sphingomyelins (SMs) are order-imposing phospholipids in cell membranes which
      interact favorably with cholesterol. The hydrophobic part of SM constitutes a
      long-chain base with an amide-linked acyl chain, whereas the polar head group is
      phosphocholine. The long-chain base has a free hydroxyl group in position 3,
      which is an important donor/acceptor in hydrogen bonding. In newborn mammals, a
      SM in which a palmitic acid is esterified to the 3-OH has been reported. We have
      synthesized this SM analog (3O-P-PSM) and studied its properties in bilayer
      membranes, and also determined its interactions with cholesterol. Fully hydrated
      3O-P-PSM bilayers underwent a gel-to-liquid crystalline phase transition at 55.5 
      degrees C (DeltaH 8 kcal/mol), which is about 15  degrees C higher than the phase
      transition temperature of PSM. The 3O-P-PSM displayed rather poor miscibility
      with PSM in mixed bilayers, suggesting that the third acyl chain interfered
      significantly with lateral interactions. Bilayers made from 3O-P-PSM were much
      more resistant to detergent-induced solubilization than bilayers made from PSM.
      In binary bilayers, cholesterol was able to destabilize the gel phase, and order
      the fluid phase of 3O-P-PSM, in a concentration-dependent manner. Cholesterol was
      also able to form sterol-enriched ordered domains with 3O-P-PSM in fluid POPC
      bilayers. The interaction between cholesterol and 3O-P-PSM was not, however, as
      favorable as the interaction between cholesterol and PSM. It is unclear what
      physiological role 3O-P-PSM could play in newborn mammalian membranes. However,
      it is clear that 3O-P-PSM will form more highly ordered domains than PSM while
      still having a limited ability to interact with cholesterol.

PMID- 21893028
TI  - Genetic dissection of proteolytic and non-proteolytic contributions of MT1-MMP to
      macrophage invasion.
AB  - MT1-MMP/MMP-14 is a major invasion-promoting membrane protease expressed in
      macrophages. In addition to its proteolytic activity that degrades the
      extracellular matrix, MT1-MMP also boosts ATP production in cells in a manner
      independent of its proteolytic activity. It remains unclear to what extent the
      proteolytic and energy-boosting activities of MT1-MMP contribute to macrophage
      invasion. Recently, we demonstrated that the cytoplasmic tail of MT1-MMP makes
      use of APBA3/Mint3 to activate HIF-1 and thereby boosts glycolysis for ATP
      production. Here, we used Apba3(-/-) macrophages to dissect the contribution of
      the proteolytic and the energy-boosting activities of MT1-MMP. The proteolytic
      activity of MT1-MMP was not affected by the lack of APBA3 in macrophages. Apba3(
      /-) and Mmp14(-/-) macrophages exhibited a 55% reduction of ATP levels compared
      to wild-type (WT) cells and the rate of motility of the mutant cells was
      accordingly reduced. In contrast, matrigel invasion by Mmp14(-/-) and Apba3(-/-)
      macrophages was reduced to 24% and 55.4%, respectively, of the level observed in
      WT cells. These results represent the first attempt to dissect the contribution
      of the two invasion-promoting activities of MT1-MMP to macrophage invasion.

PMID- 21893029
TI  - TNF-alpha increases cardiac fibroblast lysyl oxidase expression through TGF-beta
      and PI3Kinase signaling pathways.
AB  - TNF-alpha is a proinflammatory cytokine that is upregulated in many cardiac
      diseases. The increase of TNF-alpha expression affects both heart function and
      the structure of the extracellular matrix. Lysyl oxidase (LOX) is a key enzyme
      responsible for the maturation of extracellular matrix proteins, including
      collagens type I and III. In this study, we investigated the regulation of LOX
      expression and activity by TNF-alpha using adult rat cardiac fibroblasts. Our
      results indicate that TNF-alpha has a dichotomous effect on LOX expression by
      cardiac fibroblasts. Low dose TNF-alpha (1-5 ng/ml) decreased LOX expression,
      whereas higher doses (10-30 ng/ml) increased expression. The higher dose TNF
      alpha effect on LOX expression was attenuated by the inhibition of PI3Kinase/Akt
      pathway. TGF-beta1 signaling played a significant role in mediating the TNF-alpha
      effect. TNF-alpha increased the expression of TGF-beta, and TGF-beta receptors
      type I and II, and also stimulated Smad3 phosphorylation. Inhibition of TGF-beta
      receptor I or Smad3 prevented increased LOX expression by TNF-alpha. These
      findings indicate that TNF-alpha stimulated LOX expression may play an important
      role in progressive cardiac fibrosis.

PMID- 21893030
TI  - Vaspin protects vascular endothelial cells against free fatty acid-induced
      apoptosis through a phosphatidylinositol 3-kinase/Akt pathway.
AB  - Vaspin, an adipocytokine recently identified in a rat model of type 2 diabetes,
      has been suggested to have an insulin-sensitizing effect. However, the exact
      mechanism underlying this action has not been fully elucidated. Furthermore, the
      specific function of vaspin is largely unknown, especially in vascular cells. We
      examined whether vaspin affects the insulin-signaling pathway in cultured
      endothelial cells and is capable of preventing free fatty acid (FFA)-induced
      apoptosis in endothelial cells through its insulin sensitizing effect,
      specifically, through its stimulatory effect on PI3-kinase/Akt signaling
      pathways. Vaspin significantly increased Akt phosphorylation and prevented the
      impairment of Akt phosphorylation by linoleic acid (LA) in insulin-stimulated
      endothelial cells, which effects were abolished by pretreatment with the PI3
      kinase inhibitor, Wortmannin. Moreover, pretreatment with vaspin prevented LA
      induced apoptosis in insulin-stimulated endothelial cells; this anti-apoptotic
      effect of vaspin was also eliminated by pretreatment with Wortmannin. The present
      study indicates that vaspin protects vascular endothelial cells from FFA-induced
      apoptosis through upregulation of the PI3-kinase/Akt signaling pathway. Our study
      is the first to demonstrate that vascular cells can be targets of vaspin. Our
      results further suggest that vaspin could have beneficial effects on the
      atherosclerosis.

PMID- 21893027
TI  - The Bam machine: a molecular cooper.
AB  - The bacterial outer membrane (OM) is an exceptional biological structure with a
      unique composition that contributes significantly to the resiliency of Gram
      negative bacteria. Since all OM components are synthesized in the cytosol, the
      cell must efficiently transport OM-specific lipids and proteins across the cell
      envelope and stably integrate them into a growing membrane. In this review, we
      discuss the challenges associated with these processes and detail the elegant
      solutions that cells have evolved to address the topological problem of OM
      biogenesis. Special attention will be paid to the Bam machine, a highly conserved
      multiprotein complex that facilitates OM beta-barrel folding. This article is
      part of a Special Issue entitled: Protein Folding in Membranes.

PMID- 21893031
TI  - CD4 T cell dependent tumor immunity stimulated by dendritic cell based vaccine.
AB  - CD8 CTLs have been accountable for the major effector cells responsible for the
      rejection of tumor cells. And CD40 signaling and IL-12 have been shown to be the
      essential pathways involved in the activation process. Immunizing mice with
      dendritic cells transduced with an adenovirus expressing the human melanoma
      antigen gp 100, an immunization strategy of xenoimmunization, stimulated potent
      tumor protection dependent on effective CD4 T cells in the absence of CD8 T
      cells. Further studies revealed that neither CD40 signaling nor IL-12 was
      indispensable for the activation of dendritic and CD4 T cells in this model.
      Stimulation of effective antitumor immunity targeting the self-antigen did not
      elicit autoimmunity. The implications of this study were discussed.

PMID- 21893032
TI  - Numblike and Numb differentially affect p53 and Sonic Hedgehog signaling.
AB  - Numb serves as a key regulator of Notch and Sonic Hedgehog signaling and also
      modulates p53 protein levels. Numblike is a highly conserved homolog to mammalian
      Numb, but considerably less is known about its function. To address the role of
      Numblike, we have generated a mouse embryonic stem (ES) cell line, Nbl(TetOn), in
      which expression of Numblike can be induced and analyzed the effect of activation
      of Numblike. Induction of Numblike, similar to Numb, reduced the amount of Notch
      receptor, whereas Numblike differed from Numb with regard to p53 and Shh
      signaling. In contrast to Numb, Numblike did not elevate the level of p53 protein
      and Numblike potentiated, rather than reduced, the immediate downstream response
      of Shh signaling. In keeping with a role for Numblike in potentiating Shh
      signaling, Shh and Numblike synergistically increased the proportion of ES cells
      expressing pluripotency markers. In conclusion, the data demonstrate that Numb
      and Numblike have evolved to acquire at least partially distinct functions.

PMID- 21893033
TI  - Regular exercise prevents high-sucrose diet-induced fatty liver via improvement
      of hepatic lipid metabolism.
AB  - Fatty liver is known as the initial stage in nonalcoholic fatty liver disease.
      Epidemiological studies have shown that regular exercise prevents accumulation of
      hepatic lipids, although the underlying mechanism is unclear. The purpose of this
      study was to investigate the effect of exercise on fatty liver associated with
      hepatic lipid metabolism. KK/Ta mice (6 weeks old) were divided into sedentary
      and exercise groups and compared with sedentary Balb/c mice. All the mice were
      fed a high-sucrose diet for 12 weeks. The KK/Ta mice in the exercise group
      performed a treadmill running exercise at 20 m/min for 30 min (3 times per week).
      Twelve weeks of regular exercise suppressed the accumulation of lipid in the
      liver, along with reduction in the level of lipid in the plasma. The levels of
      carnitine palmitoyl transferase II, acyl-coenzyme A dehydrogenase, and
      trifunctional enzyme, which are rate-limiting enzymes in fatty acid oxidation in
      the liver, were elevated by exercise. In addition, the expression of fatty acid
      synthase, a key lipogenetic enzyme, was reduced by exercise. Furthermore, regular
      exercise decreased the expression of heat shock protein 47, a marker of hepatic
      fibrosis, in the liver. Our results suggest that regular exercise prevents fatty
      liver via improvement of hepatic lipid metabolism.

PMID- 21893034
TI  - Alternative splicings on p53, BRCA1 and PTEN genes involved in breast cancer.
AB  - Alternative splicing is a major contributor to transcriptome and proteome
      diversity, which can lead to the deregulation of crucial cellular processes and
      have been associated with a variety of human diseases including cancer. As p53,
      BRCA1, and PTEN proteins have a key role in preventing breast cancer formation,
      cancer-associated splicing variants of these tumor suppressor genes are potential
      molecular markers and may contribute to the development of diagnostic and
      prognostic methods. In the present review, we summarize these tumor suppressor
      genes at a viewpoint of alternative splicing involved in breast cancer.

PMID- 21893035
TI  - Acacetin inhibits VEGF expression, tumor angiogenesis and growth through AKT/HIF
      1alpha pathway.
AB  - Acacetin (5,7-dihydroxy-4'-methoxyflavone) is a flavone compound, some of which
      have anti-cancerous effects. Vascular endothelial growth factor (VEGF) plays an
      important role in angiogenesis and tumor growth. In this study, we found that
      acacetin decreased the steady level of VEGF mRNA level and inhibited VEGF
      transcriptional activation. To further determine the potential mechanism of
      acacetin in inhibiting VEGF expression, we showed that acacetin inhibited HIF
      1alpha expression and AKT activation. Over-expression of HIF-1alpha or AKT
      restored acacetin-decreasing VEGF transcriptional activation, indicating that AKT
      and HIF-1 are the essential downstream targets of acacetin for inhibiting VEGF
      expression in the cells. Moreover, acacetin significantly inhibited ovarian
      cancer cell-induced angiogenesis and tumor growth in vivo through inhibiting HIF
      1alpha and VEGF expression. Acacetin did not change HIF-1alpha mRNA level, but
      inhibited HIF-1alpha protein level through increasing its degradation and
      decreasing its stability. These results indicate that acacetin may be a useful
      natural compound for ovarian cancer prevention and treatment.

PMID- 21893036
TI  - Loss of DLK expression in WI-38 human diploid fibroblasts induces a senescent
      like proliferation arrest.
AB  - DLK, a serine/threonine kinase that functions as an upstream activator of the
      mitogen-activated protein kinase (MAPK) pathways, has been shown to play a role
      in development, cell differentiation, apoptosis and neuronal response to injury.
      Interestingly, recent studies have shown that DLK may also be required for cell
      proliferation, although little is known about its specific functions. To start
      addressing this issue, we studied how DLK expression is modulated during cell
      cycle progression and what effect DLK depletion has on cell proliferation in WI
      38 fibroblasts. Our results indicate that DLK protein levels are low in serum
      starved cells, but that serum addition markedly stimulated it. Moreover, RNA
      interference experiments demonstrate that DLK is required for ERK activity,
      expression of the cell cycle regulator cyclin D1 and proliferation of WI-38
      cells. DLK-depleted cells also show a senescent phenotype as revealed by
      senescence-associated galactosidase activity and up-regulation of the senescence
      pathway proteins p53 and p21. Consistent with a role for p53 in this response,
      inhibition of p53 expression by RNA interference significantly alleviated
      senescence induced by DLK knockdown. Together, these findings indicate that DLK
      participates in cell proliferation and/or survival, at least in part, by
      modulating the expression of cell cycle regulatory proteins.

PMID- 21893037
TI  - Phospholipase D2 activation by p38 MAP kinase is involved in neurite outgrowth.
AB  - p38 mitogen-activated protein (MAP) kinase plays an important role in neurite
      outgrowth. However, the underlying molecular mechanism(s) remains unclear. Here,
      we demonstrate that phospholipase D2 (PLD2) mediates p38 signaling in neurite
      outgrowth. Stimulation of rat pheochromocytoma PC12 cells with nerve growth
      factor activated PLD2 and augmented neurite outgrowth, both of which were
      inhibited by pharmacological suppression of p38. Overexpression of constitutively
      active MAP kinase kinase 6 (MKK6-CA) activated coexpressed PLD2 in PC12 and mouse
      neuroblastoma N1E-115 cells. Overexpression of wild-type PLD2 in these cells
      strongly augmented the neurite outgrowth induced by MKK6-CA, whereas lipase
      deficient PLD2 suppressed it. These findings provide evidence that PLD2 functions
      as a downstream molecule of p38 in the neurite outgrowth signaling cascade.

PMID- 21893038
TI  - Cell death induced by novel procaspase-3 activators can be reduced by growth
      factors.
AB  - Caspase-3 is known as the key executioner caspase, activated in both the
      intrinsic and extrinsic apoptotic pathway, and an effector far downstream in the
      apoptotic cascade. Procaspase-activating compound-1 (PAC-1) and 1541 were
      launched as direct activators of procaspase-3 to caspase-3, and anticipated to be
      promising therapeutic agents for the treatment of cancer. PAC-1 has recently been
      evaluated in a phase I preclinical trial. However, little is known about the
      effect of these substances in cells. Activation of caspase-3 in whole cells may
      be more complicated than thought, as it is likely that this key protease is
      tightly regulated both in development and apoptosis. In this study, we
      investigated the effect of epidermal growth factor (EGF) on PAC-1-induced caspase
      3 activity and cell death. We show that EGF can block caspase-3 activity
      generated by PAC-1, and protect both PC12 cells and primary cerebellar granule
      neurons against PAC-1-induced death. Similar results were obtained with 1541.
      Both substances reduced cellular p-ERK levels. Crosstalk between caspase-3 and
      growth factor signaling pathways may present a challenge for the use of such
      caspase-3-activating substances in cancer therapy, since aberrant growth factor
      signaling is frequently seen in malignant cells. This study adds important
      knowledge about cellular effects of procaspase-3 activators like PAC-1 and 1541.
      Effects mediated by these substances may also contribute to the understanding of
      caspase signaling in cells.

PMID- 21893039
TI  - Protein tyrosine nitration in the cell cycle.
AB  - Nitration of tyrosine residues in proteins is associated with cell response to
      oxidative/nitrosative stress. Tyrosine nitration is relatively low abundant post
      translational modification that may affect protein functions. Little is known
      about the extent of protein tyrosine nitration in cells during progression
      through the cell cycle. Here we report identification of proteins enriched for
      tyrosine nitration in cells synchronized in G0/G1, S or G2/M phases of the cell
      cycle. We identified 27 proteins in cells synchronized in G0/G1 phase, 37
      proteins in S phase synchronized cells, and 12 proteins related to G2/M phase.
      Nineteen of the identified proteins were previously described as regulators of
      cell proliferation. Thus, our data indicate which tyrosine nitrated proteins may
      affect regulation of the cell cycle.

PMID- 21893040
TI  - Oligomerization of an archaeal group II chaperonin is mediated by N-terminal salt
      bridges.
AB  - Group II chaperonins (Cpns) are essential mediators of cellular protein folding
      in eukaryotes and archaea. They consist of two back-to-back rings forming
      symmetrical cavities in which non-native substrates undergo appropriate folding,
      but the primary structural basis for the double ring formation remains unclear.
      To address this, we carried out systematic mutagenesis on the Cpn from the
      hyperthermophilic archaeon Pyrococcus furiosus, which is assembled from identical
      subunits. In our study, (21)GRDAQRMNIL(30) was found to be a critical domain for
      double ring formation. Deletion of this section stepwise beyond residue 20
      resulted in failure to assemble double-ring oligomers and the progressive loss of
      chaperone function. A key domain spanning the residues 21-50 that is essential
      for the formation of tetramers that appear to be the intermediates for double
      ring assembly. Mutation of either Arg22 to Ala22 or Glu37 to Ala37 resulted in
      similar defects in double-ring assembly and functional deficits. A mutant with
      Arg22 and Glu37 switched assembled double rings efficiently and exhibited
      chaperone functions similar to the wild-type. Therefore, Arg22 and Glu37 could
      form inter-ring salt bridges critical for double ring formation. In addition,
      Asn28 and Ile29 were found to contribute significantly to ring formation.
      Sequence alignment revealed that these four residues are highly conserved among
      group II Cpns. This is the first report of a comprehensive N-terminal mutational
      analysis for elucidating the oligomerization of group II Cpns.

PMID- 21893041
TI  - Berberine exerts anti-adipogenic activity through up-regulation of C/EBP
      inhibitors, CHOP and DEC2.
AB  - Berberine exerts an anti-adipogenic activity that is associated with the down
      regulation of C/EBPalpha and PPARgamma. Stimulation of AMP-activated kinase
      (AMPK) caused by inhibition of mitochondrial respiration has been suggested to
      underlie such molecular regulation. In the present study, we show that berberine
      up-regulated the expression of two different sets of C/EBP inhibitors, CHOP and
      DEC2, while down-modulating C/EBPalpha, PPARgamma and other adipogenic markers
      and effectors in differentiating 3T3-L1 preadipocytes and mature adipocytes. Data
      also suggested that the berberine-induced up-regulation of CHOP and DEC2 was
      attributable to selective activation of an unfolded protein response (UPR) and
      modified extracellular environment, respectively. As a result, the anti
      adipogenic activity of berberine was diminished remarkably by adjusting the
      differentiation culture media and limitedly but consistently by knockdown of CHOP
      expression. Together, up-regulation of C/EBP inhibitors appears to underlie the
      berberine-induced repression of C/EBPalpha and PPARgamma and, so, the inhibition
      of adipogenesis.

PMID- 21893042
TI  - Palmitate alters the rhythmic expression of molecular clock genes and orexigenic
      neuropeptide Y mRNA levels within immortalized, hypothalamic neurons.
AB  - The control of energy homeostasis within the hypothalamus is under the regulated
      control of homeostatic hormones, nutrients and the expression of neuropeptides
      that alter feeding behavior. Elevated levels of palmitate, a predominant
      saturated fatty acid in diet and fatty acid biosynthesis, alter cellular
      function. For instance, a key mechanism involved in the development of insulin
      resistance is lipotoxicity, through increased circulating saturated fatty acids.
      Although many studies have begun to determine the underlying mechanisms of
      lipotoxicity in peripheral tissues, little is known about the effects of excess
      lipids in the brain. To determine these mechanisms we used an immortalized,
      clonal, hypothalamic cell line, mHypoE-44, to demonstrate that palmitate directly
      alters the expression of molecular clock components, by increasing Bmal1 and
      Clock, or by decreasing Per2, and Rev-erbalpha, their mRNA levels and altering
      their rhythmic period within individual neurons. We found that these neurons
      endogenously express the orexigenic neuropeptides NPY and AgRP, thus we
      determined that palmitate administration alters the mRNA expression of these
      neuropeptides as well. Palmitate treatment causes a significant increase in NPY
      mRNA levels and significantly alters the phase of rhythmic expression. We
      explored the link between AMPK and the expression of neuropeptide Y using the
      AMPK inhibitor compound C and the AMP analog AICAR. AMPK inhibition decreased NPY
      mRNA. AICAR also elevated basal NPY, but prevented the palmitate-mediated
      increase in NPY mRNA levels. We postulate that this palmitate-mediated increase
      in NPY and AgRP synthesis may initiate a detrimental positive feedback loop
      leading to increased energy consumption.

PMID- 21893043
TI  - Identification of the site of binding of sulfated, low molecular weight lignins
      on thrombin.
AB  - Sulfated, low molecular weight lignins (LMWLs), designed recently as
      macromolecular mimetics of the low molecular weight heparins (LMWHs), were found
      to exhibit a novel allosteric mechanism of inhibition of human thrombin, factor
      Xa and plasmin, which translates into potent human blood anticoagulation
      potential. To identify the site of binding of sulfated LMWLs, a panel of site
      directed thrombin mutants was studied. Substitution of alanine for Arg(93) or
      Arg(175) induced a 7-8-fold decrease in inhibition potency, while Arg(165)Ala,
      Lys(169)Ala, Arg(173)Ala and Arg(233)Ala thrombin mutants displayed a 2-4-fold
      decrease. Other exosite 2 residues including those that play an important role in
      heparin binding, such as Arg(101), Lys(235), Lys(236) and Lys(240), did not
      induce any deficiency in sulfated LMWL activity. Thrombin mutants with multiple
      alanine substitution of basic residues showed a progressively greater defect in
      inhibition potency. Comparison of thrombin, factor Xa, factor IXa and factor VIIa
      primary sequences reiterated Arg(93) and Arg(175) as residues likely to be
      targeted by sulfated LMWLs. The identification of a novel site on thrombin with
      capability of allosteric modulation is expected to greatly assist the design of
      new regulators based on the sulfated LMWL scaffold.

PMID- 21893044
TI  - Hydrogen sulphide inhibits cardiomyocyte hypertrophy by up-regulating miR-133a.
AB  - Hydrogen sulphide (H(2)S) has been shown to play a crucial role in cardiovascular
      physiology and disease. However, there is no information about the possible role
      of H(2)S in cardiomyocyte hypertrophy (CH). Our results showed that pretreatment
      with NaHS, an H(2)S donor, significantly reduced [(3)H]-leucine incorporation,
      cell surface area, mRNA expression of brain natriuretic peptide (BNP),
      intracellular reactive oxygen species (ROS), miR-21 and increased atrial
      natriuretic peptide (ANP) and miR-133a expression in hypertrophic cardiomyocytes.
      Anti-miR133a inhibitor transfection partly reduced the anti-hypertrophic effect
      of NaHS. In conclusion, H(2)S is a direct inhibitor of CH; it acts by increasing
      miR-133a and inhibiting the increase in intracellular ROS.

PMID- 21893045
TI  - Differential expression of co-signal molecules and migratory properties in four
      distinct subsets of migratory dendritic cells from the oral mucosa.
AB  - Variations in co-signal ligand expression and cytokine production greatly
      influence the antigen-presenting properties of migrating DCs in regional lymph
      nodes (RLNs). Here we investigated DCs migrating from the oral mucosa using CD326
      and CD103 antigens for discriminate CD207(+) Langerhans cells (LCs) from CD207(+)
      submucosal DCs (SMDCs). Similar to DCs migrating from the skin, we identified
      four distinct oral mucosal DC (OMDC) subsets, CD11c(hi)CD207(-)CD103(
      )CD326(int)CD11b(hi) (F1; resident CD11b(hi) SMDCs), CD11c(int/lo)CD207(-)CD103(
      )CD326(lo)CD11b(int/hi) (F2; newly recruited blood-derived SMDCs),
      CD11c(int/lo)CD207(+)CD103(+)CD326(int/hi)CD11b(lo) (CD103(+) F3; resident
      CD207(+) SMDCs), and CD11c(int/lo)CD207(+)CD103(-)CD326(int/hi)CD11b(lo) (CD103(
      ) F3; resident LCs). F1 DCs migrated rapidly after fluorescein isothiocyanate
      (FITC) painting and expressed notably high levels of CD86, CD273, and CD274 at an
      earlier time point. In contrast, CD103(-) LCs expressing the highest levels of
      the epithelial cell adhesion molecule CD326 accounted for a minor subset at the
      earlier time point, but increased slowly with CD103(+)CD207(+) SMDCs. However,
      their expression of CD86, CD273, and CD274 was very limited. The delayed
      migration and limited induction of co-signal ligands suggest that roles of OMLCs
      are distinct from those of the other three DC subsets. The identification of
      distinct subsets of OMDCs in RLNs may benefit efforts to determine the functional
      specialization of each subset in T cell responses against orally administrated
      antigens.

PMID- 21893046
TI  - Modulation of the ribonucleotide reductase M1-gemcitabine interaction in vivo by
      N-ethylmaleimide.
AB  - Ribonucleotide reductase M1 (RRM1) is the regulatory subunit of the holoenzyme
      that catalyzes the conversion of ribonucleotides to 2'-deoxyribonucleotides. Its
      function is indispensible in cell proliferation and DNA repair. It also serves as
      a biomarker of therapeutic efficacy of the antimetabolite drug gemcitabine (2',2'
      difluoro-2'-deoxycytidine) in various malignancies. However, a mechanistic
      explanation remains to be determined. This study investigated how the alkylating
      agent N-ethylmaleimide (NEM) interacts with the inhibitory activity of
      gemcitabine on its target protein RRM1 in vivo. We found, when cells were treated
      with gemcitabine in the presence of NEM, a novel 110 kDa band, along with the 90
      kDa native RRM1 band, appeared in immunoblots. This 110 kDa band was identified
      as RRM1 by mass spectrometry (LC-MS/MS) and represented a conformational change
      resulting from covalent labeling by gemcitabine. It is specific to
      gemcitabine/NEM, among 11 other chemotherapy drugs tested. It was also detectable
      in human tumor xenografts in mice treated with gemcitabine. Among mutations of
      seven residues essential for RRM1 function, C218A, C429A, and E431A abolished the
      conformational change, while N427A, C787A, and C790A diminished it. C444A was
      unique since it was able to alter the conformation even in absence of gemcitabine
      treatment. We conclude that the thiol alkylator NEM can stabilize the gemcitabine
      induced conformational change of RRM1, and this stabilized RRM1 conformation has
      the potential to serve as a specific biomarker of gemcitabine's therapeutic
      efficacy.

PMID- 21893047
TI  - Effects of bacterial products on enterocyte-macrophage interactions in vitro.
AB  - We describe a coculture model of a human intestinal epithelial cell line and
      human peripheral blood monocytes in which monocytes differentiate into cells with
      features of resident intestinal macrophages. Caco-2 cells are grown on the lower
      surface of a semipermeable filter with pore size of 3 MUm (Transwells) until they
      differentiate into enterocytes. Peripheral-blood monocytes are added and the co
      culture incubated for two days. Monocytes migrate through the pores of the
      membrane, come into direct contact with the basolateral surfaces of the
      epithelial cell monolayer, and develop characteristics of resident intestinal
      macrophages including downregulation of CD14 expression and reduced pro
      inflammatory cytokine responses (IL-8, TNF and IL-1beta) to bacterial products.
      The apical application of lipopolysaccharide (LPS) and muramyl dipeptide (MDP)
      resulted in an increased number of integrated monocytes, but abrogated the
      downregulation of CD14 expression and the diminished cytokine responses. MDP also
      reduced tight-junctional integrity, whilst LPS had no effect. These data indicate
      that LPS and MDP have significant pathophysiological effects on enterocyte
      monocyte interactions, and confirm other studies that demonstrate that
      enterocytes and their products influence monocyte differentiation. This model may
      be useful in providing insights into the interaction between monocytes,
      epithelial cells and intestinal bacteria in health and disease.

PMID- 21893048
TI  - Starch-binding domain-containing protein 1 (Stbd1) and glycogen metabolism:
      Identification of the Atg8 family interacting motif (AIM) in Stbd1 required for
      interaction with GABARAPL1.
AB  - Glycogen, a branched polymer of glucose, acts as an intracellular carbon and
      energy reserve in many tissues and cell types. An important pathway for its
      degradation is by transport to lysosomes in an autophagy-like process. It has
      been proposed that starch-binding domain-containing protein 1 (Stbd1) may
      participate in this mechanism by anchoring glycogen to intracellular membranes.
      In addition, Stbd1 has been reported to interact with a known autophagy protein,
      GABARAPL1, a member of the Atg8 family. Here, we confirm this interaction and
      identify an Atg8 interacting motif (AIM) in Stbd1 necessary for GABARAPL1 binding
      as judged by co-immunoprecipitation from cell extracts and co-localization in
      cells as evidenced by immunofluorescence microscopy. The AIM sequence of Stbd1
      (200)HEEWEMV(206) lies within a predicted disordered region of the molecule and
      fits the consensus of other AIM sequences in cargo-specifying proteins such as
      p62 and Nix. Mutation of the AIM, including single point mutations of either W203
      or V206, eliminated the co-localization of Stbd1 with both over-expressed and
      endogenous GABARAPL1. Stbd1 may therefore function as a novel cargo binding
      protein that delivers glycogen to lysosomes in an autophagic pathway that could
      be termed "glycophagy".

PMID- 21893050
TI  - Association of N-terminal pro brain natriuretic peptide and impaired aortic
      elastic property in hypertensive patients.
AB  - BACKGROUND: N-terminal pro brain natriuretic peptide (NT-proBNP) is closely
      related to risk stratification in many cardiovascular diseases. The objective of
      this study was to evaluate the association of NT-proBNP and impaired aortic
      elastic property in hypertensive patients. METHODS: One hundred fifty-five
      hypertensive patients without obvious cardiac dysfunction were included and
      divided in tertiles based on their NT-proBNP concentration. Eighty-six
      normotensive healthy volunteers were also enrolled as controls. All subjects
      underwent Doppler echocardiography to assess cardiac parameters and aortic
      distensibility index. Plasma NT-proBNP was measured by electrochemiluminescence.
      RESULTS: The parameters of aortic elastic property were decreased and NT-proBNP
      was significantly increased in hypertensive patients compared with controls (all
      P<0.05). Among hypertensive patients, higher NT-proBNP tertiles were associated
      with larger systolic and diastolic aortic diameters, longer deceleration time of
      the E wave velocity (DT) and isovolumic relaxation time; decreased E/A ratio and
      more percent of diastolic dysfunction. The parameters of aortic elastic property
      showed stepwise decreases from the first tertiles to the third tertiles (P<0.05).
      Multiple linear regression analysis showed that concentrations of NT-proBNP were
      significantly correlated with age and impaired aortic distensibility.
      CONCLUSIONS: NT-proBNP is a marker for impaired aortic elastic property in
      hypertensive patients. Measurement of NT-proBNP could be indicated in
      hypertensive patients for further risk stratification.

PMID- 21893049
TI  - Characterization of zebrafish dysferlin by morpholino knockdown.
AB  - Mutations in the gene encoding dysferlin cause two distinct muscular dystrophy
      phenotypes: limb-girdle muscular dystrophy type 2B (LGMD-2B) and Miyoshi myopathy
      (MM). Dysferlin is a large transmembrane protein involved in myoblast fusion and
      membrane resealing. Zebrafish represent an ideal animal model to use for studying
      muscle disease including abnormalities of dysferlin. cDNAs of zebrafish dysferlin
      were cloned (6.3 kb) and the predicted amino acid sequences, showed 68%
      similarity to predicted amino acid sequences of mammalian dysferlin. The
      expression of dysferlin was mainly in skeletal muscle, heart and eye, and the
      expression could be detected as early as 11h post fertilization (hpf). Three
      different antisense oligonucleotide morpholinos were targeted to inhibit
      translation of this dysferlin mRNA and the morpholino-injected fish showed marked
      muscle disorganization which could be detected by birefringence assay. Western
      blot analysis using dysferlin antibodies showed that the expression of dysferlin
      was reduced in each of the three morphants. Dysferlin expression was shown to be
      reduced at the myosepta of zebrafish muscle using immunohistochemistry, although
      the expression of other muscle membrane components, dystrophin, laminin, beta
      dystroglycan were detected normally. Our data suggest that zebrafish dysferlin
      expression is involved in stabilizing muscle structures and its downregulation
      causes muscle disorganization.

PMID- 21893051
TI  - Mutational analysis of JAG1 gene in non-syndromic tetralogy of Fallot children.
AB  - BACKGROUND: JAG1 is an evolutionarily conserved ligand for Notch receptor and
      functions in the cell fate decisions, cell-cell interactions throughout the
      development of heart especially right heart development. Tetralogy of Fallot
      (TOF) is essentially a right sided heart disease with characteristic features of
      ventricular septal defect, right ventricular outflow tract obstruction, aortic
      dextroposition and right ventricular hypertrophy. Hence, the present study was
      investigated to identify mutations of JAG1 gene in an Indian cohort of patients
      with TOF. METHODS: The clinical data and blood samples from 84 unrelated subjects
      with TOF were collected and evaluated in comparison with 87 healthy individuals.
      PCR based single strand conformation polymorphism analysis and subsequent
      bidirectional DNA sequencing of conformers was carried in the exon 6 of JAG1
      gene. RESULTS: The DNA sequences aligned with NCBI-BLAST led to the
      identification of four novel variations including one nonsense 765 C>A, two
      missense 814 G>T, 834 G>T; and one silent alteration 816 G>T in TOF patients. The
      protein structure of JAG1 predicts that these variations effect first and second
      epidermal growth factor like repeat and might disturb ligand-receptor binding
      ability. The presence of similar variations was not observed in healthy controls.
      The software CLUSTAL-W showed the inter species conservation of altered amino
      acids in missense mutations. CONCLUSION: Disease-associating novel JAG1 gene
      variations were found in TOF patients, and seem to play an important role in the
      causation of the disease.

PMID- 21893052
TI  - Plasma aluminum is a risk factor for oxidative stress and inflammation status in
      hemodialysis patients.
AB  - OBJECTIVES: The association between aluminum (Al), essential trace metals,
      oxidative stress, and inflammation status was evaluated in hemodialysis patients.
      DESIGN AND METHODS: Biochemical parameters in blood were determined in long-term
      hemodialysis patients (n=69) and age- and sex-matched healthy individuals (n=30).
      RESULTS: Compared with healthy subjects, patients had significantly higher
      concentrations of plasma Al. Elevated Al was negatively associated with the
      essential metals zinc, selenium, and iron. Al concentrations were strongly and
      positively correlated with contents of the oxidation products malondialdehyde and
      protein carbonyl. Inverse relationships were observed between Al concentrations
      and reduced concentrations of glutathione, beta-carotene, vitamin C, and vitamin
      E. Patients were also observed to have significantly increased production values
      of plasma high-sensitivity C-reactive protein, tumor necrosis factor-alpha, and
      interleukin-5. CONCLUSION: An increased plasma Al concentration is associated
      with disturbed concentrations of essential metals, increased oxidative stress,
      and increased inflammation status in hemodialysis patients.

PMID- 21893053
TI  - Cryopreservation-induced alterations in protein tyrosine phosphorylation of
      spermatozoa from different portions of the boar ejaculate.
AB  - Previous studies have shown that boar sperm quality after cryopreservation
      differs depending on the ejaculate fraction used and that spermatozoa contained
      in the first 10mL (P1) of the sperm-rich fraction (SRF) show better cryosurvival
      than those in the SRF-P1. Since protein tyrosine phosphorylation (PTP) in
      spermatozoa is related with the tolerance of spermatozoa to frozen storage and
      cryocapacitation, we assessed the dynamics of cryopreservation-induced PTP and
      intracellular calcium ([Ca(2+)]i) in spermatozoa, using flow cytometry, from P1
      and SRF-P1 of the boar ejaculate at different stages of cryopreservation. Sperm
      kinetics, assessed using a computer-assisted semen analyzer, did not differ
      between P1 and SRF-P1 during cryopreservation but the decrease in sperm velocity
      during cryopreservation was significant (P<0.05) in SRF-P1 compared to P1. There
      were no significant differences in percentages of spermatozoa with high [Ca(2+)]i
      between P1 and SRF-P1 in fresh as well as in frozen-thawed semen. A higher
      (P<0.001) proportion of spermatozoa displayed PTP during the course of
      cryopreservation indicating a definite effect of the cryopreservation process on
      sperm PTP. The proportion of spermatozoa with PTP did not differ significantly
      between portions of the boar ejaculate. However at any given step during
      cryopreservation the percentage of spermatozoa with PTP was comparatively higher
      in SRF-P1 than P1. A 32kDa tyrosine phosphorylated protein, associated with
      capacitation, appeared after cooling suggesting that cooling induces capacitation
      like changes in boar spermatozoa. In conclusion, the study has shown that the
      cryopreservation process induced PTP in spermatozoa and their proportions were
      similar between portions of SRF.

PMID- 21893054
TI  - Development and subsequent cryotolerance of domestic cat embryos cultured in
      serum-free and serum-containing media.
AB  - The objectives of this study were to examine the effects of the presence or
      absence of serum during the in vitro culturing period of domestic cat embryos on
      their developmental potential into blastocysts as well as their tolerance to
      cryopreservation using a slow-freezing method. In vitro-fertilized cat oocytes
      were incubated in a modified synthetic oviduct fluid (mSOF) containing 4 mg/mL
      bovine serum albumin (BSA) throughout culturing (BSA group) or in mSOF containing
      4 mg/mL BSA for the first 3 days followed by mSOF containing 5% fetal bovine
      serum (FBS group). The developmental potential of the embryos to the blastocyst
      and expanded blastocyst stages was evaluated 7 days after in vitro fertilization.
      The blastocysts were frozen-thawed by the slow-freezing method and cultured for 3
      days to examine their viability in vitro. There were no differences in the
      formation rates of blastocysts or expanded blastocysts, or number of cells in the
      embryos between the two groups. After cryopreservation, the hatching rates of the
      expanded blastocysts in the BSA group were significantly higher (P<0.05) than
      those of the FBS group. The postthaw viability of blastocysts was lower than that
      of expanded blastocysts irrespective of culture medium. These results indicate
      that the developmental potential of cat embryos cultured in serum-free medium is
      comparable to those cultured in serum-containing medium. Furthermore, expanded
      blastocysts produced without serum exhibit better postthaw viability than those
      produced with serum.

PMID- 21893056
TI  - The mechanisms of microgliosis and pain following peripheral nerve injury.
AB  - Microglia are the resident macrophages in the central nervous system (CNS). Any
      insult to the CNS homeostasis will induce a rapid change in microglia morphology,
      gene expression profile and functional behaviour. These responses of microglia
      have been collectively known as 'microgliosis'. Interestingly, damage to the
      nervous system outside the CNS, such as axotomy of a peripheral nerve, can lead
      to microgliosis in the spinal cord. There is a variation in the degree of
      microgliosis depending on the model of nerve injury employed for instance this
      response is more marked following traumatic nerve injury than in models of
      chemotherapy induced neuropathy. Following peripheral nerve injury nociceptive
      inputs from sensory neurons appear to be critical in triggering the development
      of spinal microgliosis. A number of signalling pathways including growth factors
      such as Neuregulin-1, matrix metalloproteases such as MMP-9 and multiple
      chemokines enable direct communication between injured primary afferents and
      microglia. In addition, we describe a group of mediators which although not
      demonstrably shown to be released from neurons are known to modulate microglial
      phenotype. There is a great functional diversity of the microglial response to
      peripheral nerve injury which includes: Cellular migration, proliferation,
      cytokine release, phagocytosis, antigen presentation and recruitment of T cells.
      It should also be noted that in certain contexts microglia may have a role in the
      resolution of neuro-inflammation. Although there is still no direct evidence
      demonstrating that spinal microglia have a role in neuropathic pain in humans,
      these patients present a pro-inflammatory cytokine profile and it is a reasonable
      hypothesis that these cells may contribute to this inflammatory response.
      Modulating microglial functions offers a novel therapeutic opportunity following
      nerve injury which ideally would involve reducing the pro-inflammatory nature of
      these cells whilst retaining their potential beneficial functions.

PMID- 21893057
TI  - Glycan microarray profiling of parasite infection sera identifies the LDNF glycan
      as a potential antigen for serodiagnosis of trichinellosis.
AB  - Diagnostic methods for parasite infections still highly depend on the
      identification of the parasites by direct methods such as microscopic examination
      of blood, stool and tissue biopsies. Serodiagnosis is often carried out to
      complement the direct methods; however, few synthetic antigens with sufficient
      sensitivity and specificity are available. Here we evaluated a glycan microarray
      approach to select for synthetic glycan antigens that could be used for
      serodiagnosis of parasitic infections. Using a glycan array containing over 250
      different glycan antigens, we identified GalNAcbeta1-4(Fucalpha1-3)GlcNAc-R
      (LDNF) as a glycan antigen that is recognized by antibodies from Trichinella
      infected individuals. We synthesized a neoglycoconjugate, consisting of five LDNF
      molecules covalently coupled to bovine serum albumin (BSA), and used this
      neoglycoconjugate as an antigen to develop a highly sensitive total-Ig ELISA for
      serological screening of trichinellosis. The results indicate that glycan
      microarrays constitute a promising technology for fast and specific
      identification of parasite glycan antigens to improve serodiagnosis of different
      parasitic infections, either using an ELISA format, or parasite-specific glycan
      arrays.

PMID- 21893058
TI  - MiR-483-5p controls angiogenesis in vitro and targets serum response factor.
AB  - Angiogenesis, a key factor in ischemic heart disease, is rapidly initiated in
      response to hypoxic or ischemic conditions. MicroRNAs (miRNAs) are endogenously
      expressed small non-coding RNAs that regulate gene expression at post
      transcriptional level. The recent discovery of the involvement of these RNAs in
      the control of angiogenesis renders them very attractive in the development of
      new approaches for restoring the angiogenic balance. In the present study, we
      explored that miR-483-5p, a microRNA embedded in the intron of insulin-like
      growth factor 2 (Igf2), acts as an endogenous angiogenesis-inhibiting factor. We
      identified that serum response factor (SRF) is one of miR-483-5p target genes.
      These findings indicated that the miR-483-5p-SRF pathway may offer a novel
      strategy for treatment with angiogenesis in ischemic heart disease patients.

PMID- 21893059
TI  - Hair cortisol levels track phylogenetic and age related differences in
      hypothalamic-pituitary-adrenal (HPA) axis activity in non-human primates.
AB  - Hair has been shown to archive a uniquely time averaged signal of endocrine
      activity, and holds attractive advantages for both laboratory and field research.
      Prior research has explored the potential of hair hormone analysis to examine
      hormone-behavior relationships. To date, no research has focused on the potential
      of the technique to investigate age-related changes or taxon differences in
      endocrine function. It is known that non-human primate infants of many taxa
      exhibit high cortisol levels after parturition, which rapidly decline with age.
      It has also been shown that hypercortisolism generally characterizes platyrrhine
      (New World monkey) endocrine function. These endocrine trends have been
      characterized using cortisol levels determined from serum, plasma, and feces.
      Here we test whether cortisol levels determined from hair recover similar
      phylogenetic and age related patterns in endocrine function in non-human
      primates. In order to test whether hair cortisol reflect infant hypercortisolism
      with significant age-related decline, hair cortisol levels are measured in
      samples from wild vervet monkeys (Chlorocebus aethiops) and captive Guinea
      baboons (Papio hamadryas papio), ranging in age from infants through juveniles.
      Further, in order to test whether platyrrhines exhibit significantly higher hair
      cortisol levels compared to strepsirrhines and catarrhines, and therefore
      faithfully recover similar signals as more traditionally used substrates (e.g.
      serum), hair cortisol levels are quantified in adult female hair samples
      collected from a broad range of non-human primate taxa. Results confirm that hair
      cortisol levels accurately reflect known phylogenetic and age related patterns of
      circulating cortisol levels. Therefore, these results suggest that hair may be an
      ideal hormone bearing substrate for research focused on the examination of
      population endocrine profiles, cross-sectional studies of endocrine function and
      taxon variation in hormone levels, as well as stable behavioral trends.

PMID- 21893060
TI  - Cardiovascular and vasoconstrictive actions of skate bradykinin in the little
      skate, Leucoraja erinacea (Elasmobranchii).
AB  - The vasoconstrictive and cardiovascular actions of a recently identified
      bradykinin (BK)-related peptide (Gly-Ile-Thr-Ser-Trp-Leu-Pro-Phe) from the little
      skate, Leucoraja erinacea were examined in the unanesthetised little skate. Intra
      arterial administration of a skate BK (0.1-1 nmolkg(-1)) produced a hypertensive
      response with a rise in blood pressure reaching a maximum elevation of 28.7+/
      4.8% over baseline (P<0.05, n=8) that was sustained for at least 12 min following
      administration of a 1 and 0.3 nmolkg(-1) dose of skate BK. Further, in vivo
      administration of 1 nmolkg(-1) skate BK induced a significant delayed increase in
      stroke volume (reaching a maximum of 54.4+/-14.7% above baseline) without
      significant effect on either cardiac output or heart rate. In vitro, skate BK
      constricted the 1st branchial, mesenteric (EC(50) 2.7*10(-9)M) and coeliac
      (EC(50) 3.1*10(-9)M) arterial preparations of the skate. In contrast, skate
      [Arg(9)]BK, the mammalian B(1) receptor agonist des-[Arg(9)]BK, and the mammalian
      B(2) receptor antagonist HOE-140 failed to induce vasoconstriction in these
      isolated arterial preparations. The vasoconstrictor actions of skate BK in the
      isolated mesenteric, coeliac and branchial arterial preparations were
      significantly inhibited when co-administrated with esculetin and phentolamine.
      Indomethacin also inhibited the vasoconstrictor actions of skate BK in the
      isolated branchial artery. We conclude that, as in mammals and teleost fish,
      multiple pathways involving at least the alpha adrenergic and leukotriene
      synthesis pathway are involved in mediating the vasoconstrictive actions of BK in
      vascular smooth muscle of the little skate.

PMID- 21893061
TI  - Evaluating the twin testosterone transfer hypothesis: a review of the empirical
      evidence.
AB  - In this paper we review the evidence that fetuses gestated with a male co-twin
      are masculinized in development, perhaps due to the influence of prenatal
      androgens: the so-called twin testosterone transfer (TTT) hypothesis. Evidence
      from studies of behavioral, perceptual, cognitive, morphological and
      physiological traits in same- and opposite-sex human twins is considered. Apart
      from two studies reporting increases in aspects of sensation-seeking for females
      with a male rather than a female co-twin, there is sparse evidence supporting the
      TTT hypothesis in behavioral studies. Outcomes from studies of perception (in
      particular otoacoustic emissions) and cognition (in particular vocabulary
      acquisition and visuo-spatial ability) provide more consistent evidence in
      support of masculinized performance in twins with a male co-twin compared to
      twins with a female co-twin. The outcomes favorable to the TTT hypothesis for
      otoacoustic emissions and visuo-spatial ability are restricted to females.
      Studies of physiology and morphology (e.g., brain volume, tooth size and 2D:4D
      ratio) also show some influence of co-twin sex, but again these effects are often
      restricted to female twins. Because females produce little endogenous
      testosterone, the effects of gestation with a male co-twin may be more pronounced
      in females than males. Thus, while uneven, the evidence for the TTT hypothesis is
      sufficient to warrant further investigation, ideally using large samples of same-
      and opposite-sex twins, along with control groups of same- and opposite-sex
      siblings when the characteristics assessed are potentially open to social
      influences.

PMID- 21893062
TI  - Comparison of GD2 binding capture ELISA assays for anti-GD2-antibodies using GD2
      coated plates and a GD2-expressing cell-based ELISA.
AB  - Two assay methods for quantification of the disialoganglioside (GD2)-specific
      binding activities of anti-GD2 monoclonal antibodies and antibody immunofusion
      proteins, such as ch14.18 and hu14.18-IL2, were developed. The methods differed
      in the use of either microtiter plates coated with purified GD2 or plates seeded
      with GD2-expressing cell lines to bind the anti-GD2 molecules. The bound
      antibodies were subsequently detected using the reactivity of the antibodies to
      an HRP-labeled anti-IgG Fc or antibodies recognizing the conjugate IL-2 part of
      the Hu 14.18IL-2 fusion protein. The bound HRP was detected using reagents such
      as orthophenylene diamine, 2, 2'-azinobis [3-ethylbenzothiazoline-6-sulfonic
      acid] or tetramethylbenzidine. The capture ELISA using GD2-coated plates was
      developed earlier in assay development and used to demonstrate assay specificity
      and to compare lot-to-lot consistency and stability of ch14.18, and Hu14.18 IL-2
      in clinical development. During this study, we found a number of issues related
      to plate-to-plate variability, GD2 lot variability, and variations due to GD2
      storage stability, etc., that frequently lead to assay failure in plates coated
      with purified GD2. The cell-based ELISA (CbELISA) using the GD2 expressing
      melanoma cell line, M21/P6, was developed as an alternative to the GD2-coated
      plate ELISA. The results on the comparability of the capture ELISA on GD2-coated
      plates and the cell-based assay show that both assays give comparable results.
      However, the cell-based assay is more consistent and reproducible. Subsequently,
      the anti-GD2 capture ELISA using the GD2-coated plate was replaced with the
      CbELISA for product lot release testing and stability assessment.

PMID- 21893063
TI  - A phage display system for the identification of novel Anisakis simplex antigens.
AB  - Anisakis simplex has been recognized as an important cause of disease in man and
      as a foodborne allergen source. Actually, this food-borne was recently identified
      as an emerging food safety risk including allergenic symptoms. This parasite
      contains a large variety of allergenic proteins enforcing the necessity to detect
      new allergens. Commonly, these efforts have been focused on the developing of
      cDNA libraries, where virtually all expressed mRNAs are present, by using
      immunoreactive patient serum or polyclonal antibodies. Phage display system is an
      alternative strategy which permits the physical binding of the genotype with the
      phenotype, since the products are expressed by the phage on its surface, thereby
      allowing more efficient selection. In this work we have constructed two libraries
      in the pJuFo phage, obtaining a primary titer of around 103 cfu/ml and an
      amplified titer of the order of 1013 cfu/ml whereas the insert sizes varied from
      0.35 to 1.2kb. Both libraries were subsequently analyzed by enrichment with
      polyclonal antibodies to an A. simplex extract and immunoreactive sera from
      patients with a clinical history of allergy to this parasite. Finally, 30 clones
      were scrutinized detecting several Anisakis candidate antigens. Actually, one
      protein, belongs to the fructose-1,6-bisphosphatase family, was found in 34% of
      scrutinized clones revealing as a promising novel A. simplex allergen. Phage
      display technology has to date not yet been applied to the identification of new
      A. simplex allergens, and the present work opens up new avenues to the
      understanding of the Anisakis allergenic process.

PMID- 21893064
TI  - Serotonin depresses feeding behaviour in ants.
AB  - Feeding behaviour is a complex functional system that relies on external signals
      and the physiological state of the animal. This is also the case in ants as they
      vary their feeding behaviour according to food characteristics, environmental
      conditions and - as they are social insects - to the colony's requirements. The
      biogenic amine serotonin (5-HT) was shown to be involved in the control and
      modulation of many actions and processes related to feeding in both vertebrates
      and invertebrates. In this study, we investigated whether 5-HT affects nectar
      feeding in ants by analysing its effect on the sucking-pump activity.
      Furthermore, we studied 5-HT association with tissues and neuronal ganglia
      involved in feeding regulation. Our results show that 5-HT promotes a dose
      dependent depression of sucrose feeding in Camponotus mus ants. Orally
      administered 5-HT diminished the intake rate by mainly decreasing the volume of
      solution taken per pump contraction, without modifying the sucrose acceptance
      threshold. Immunohistochemical studies all along the alimentary canal revealed 5
      HT-like immunoreactive processes on the foregut (oesophagus, crop and
      proventriculus), while the midgut and hindgut lacked 5-HT innervation. Although
      the frontal and suboesophageal ganglia contained 5-HT immunoreactive cell bodies,
      serotonergic innervation in the sucking-pump muscles was absent. The results are
      discussed in the frame of a role of 5-HT in feeding control in ants.

PMID- 21893065
TI  - Identification of a nucleopolyhedrovirus in winter moth populations from
      Massachusetts.
AB  - Winter moth, Operophtera brumata, originally from Europe, has invaded eastern
      Massachusetts causing widespread defoliation and damage to many deciduous tree
      species and a variety of crop plants in the infested area. We identified O.
      brumata nucleopolyhedrovirus (OpbuNPV) in winter moth larvae collected from field
      sites in Massachusetts by using PCR to amplify a 482 bp region of the baculovirus
      polyhedrin gene. Viral sequences were also detected in winter moth pupae that
      failed to emerge, suggesting that these insects may have died as a result of
      viral infection. This represents the first report of OpbuNPV in winter moth
      populations in the US.

PMID- 21893066
TI  - Previously unknown apicomplexan species infecting Iceland scallop, Chlamys
      islandica (Muller, 1776), queen scallop, Aequipecten opercularis L., and king
      scallop, Pecten maximus L.
AB  - Examination of three scallop species from three separate locations: Iceland
      scallop from Icelandic waters, king scallop from Scottish waters and queen
      scallop from Faroese and Scottish waters, revealed infections of a previously
      unknown apicomplexan parasite in all three scallop species. Developmental forms
      observed in the shells appeared to include both sexual and asexual stages of the
      parasite, i.e. merogony, gametogony and sporogony, which suggests a monoxenous
      life cycle. Meronts, gamonts, zygotes and mature oocysts were solely found in the
      muscular tissue. Zoites, which could be sporozoites and/or merozoites, were
      observed in great numbers, most frequently in muscles, both intracellular and
      free in the extracellular space. Zoites were also common inside haemocytes.
      Examination of the ultrastructure showed that the zoites contained all the major
      structures characterizing apicomplexans. This apicomplexan parasite is
      morphologically different from other apicomplexan species previously described
      from bivalves. Presently, its systematic position within the phylum Apicomplexa
      cannot be ascertained.

PMID- 21893067
TI  - Iron-coordinating tyrosine is a key determinant of NEAT domain heme transfer.
AB  - In humans, heme iron is the most abundant iron source, and bacterial pathogens
      such as Staphylococcus aureus acquire it for growth. IsdB of S. aureus acquires
      Fe(III)-protoporphyrin IX (heme) from hemoglobin for transfer to IsdC via IsdA.
      These three cell-wall-anchored Isd (iron-regulated surface determinant) proteins
      contain conserved NEAT (near iron transport) domains. The purpose of this work
      was to delineate the mechanism of heme binding and transfer between the NEAT
      domains of IsdA, IsdB, and IsdC using a combination of structural and
      spectroscopic studies. X-ray crystal structures of IsdA NEAT domain (IsdA-N1)
      variants reveal that removing the native heme-iron ligand Tyr166 is compensated
      for by iron coordination by His83 on the distal side and that no single mutation
      of distal loop residues is sufficient to perturb the IsdA-heme complex. Also,
      alternate heme-iron coordination was observed in structures of IsdA-N1 bound to
      reduced Fe(II)-protoporphyrin IX and Co(III)-protoporphyrin IX. The IsdA-N1
      structural data were correlated with heme transfer kinetics from the NEAT domains
      of IsdB and IsdC. We demonstrated that the NEAT domains transfer heme at rates
      comparable to full-length proteins. The second-order rate constant for heme
      transfer from IsdA-N1 was modestly affected (<2-fold) by the IsdA variants,
      excluding those at Tyr166. Substituting Tyr166 with Ala or Phe changed the
      reaction mechanism to one with two observable steps and decreased observed rates
      >15-fold (to 100-fold excess IsdC). We propose a heme transfer model wherein NEAT
      domain complexes pass heme iron directly from an iron-coordinating Tyr of the
      donor protein to the homologous Tyr residues of the acceptor protein.

PMID- 21893068
TI  - Dynamism in molecular chaperones.

PMID- 21893069
TI  - Binding and selectivity of the marine toxin neodysiherbaine A and its synthetic
      analogues to GluK1 and GluK2 kainate receptors.
AB  - Dysiherbaine (DH) and neodysiherbaine A (NDH) selectively bind and activate two
      kainate-type ionotropic glutamate receptors, GluK1 and GluK2. The ligand-binding
      domains of human GluK1 and GluK2 were crystallized as bound forms with a series
      of DH analogues including DH, NDH, 8-deoxy-NDH, 9-deoxy-NDH and 8,9-dideoxy-NDH
      (MSVIII-19), isolated from natural sources or prepared by total synthesis. Since
      the DH analogues exhibit a wide range of binding affinities and agonist
      efficacies, it follows that the detailed analysis of crystal structure would
      provide us with a significant opportunity to elucidate structural factors
      responsible for selective binding and some aspects of gating efficacy. We found
      that differences in three amino acids (Thr503, Ser706 and Ser726 in GluK1 and
      Ala487, Asn690 and Thr710 in GluK2) in the ligand-binding pocket generate
      differences in the binding modes of NDH to GluK1 and GluK2. Furthermore, deletion
      of the C(9) hydroxy group in NDH alters the ligand conformation such that it is
      no longer suited for binding to the GluK1 ligand-binding pocket. In GluK2, NDH
      pushes and rotates the side chain of Asn690 (substituted for Ser706 in GluK1) and
      disrupts an interdomain hydrogen bond with Glu409. The present data support the
      idea that receptor selectivities of DH analogues resulted from the differences in
      the binding modes of the ligands in GluK1/GluK2 and the steric repulsion of
      Asn690 in GluK2. All ligands, regardless of agonist efficacy, induced full domain
      closure. Consequently, ligand efficacy and domain closure did not directly
      coincide with DH analogues and the kainate receptors.

PMID- 21893070
TI  - Structural characterization of intramolecular Hg(2+) transfer between flexibly
      linked domains of mercuric ion reductase.
AB  - The enzyme mercuric ion reductase MerA is the central component of bacterial
      mercury resistance encoded by the mer operon. Many MerA proteins possess
      metallochaperone-like N-terminal domains (NmerA) that can transfer Hg(2+) to the
      catalytic core domain (Core) for reduction to Hg(0). These domains are tethered
      to the homodimeric Core by ~30-residue linkers that are susceptible to
      proteolysis, the latter of which has prevented characterization of the
      interactions of NmerA and the Core in the full-length protein. Here, we report
      purification of homogeneous full-length MerA from the Tn21 mer operon using a
      fusion protein construct and combine small-angle X-ray scattering and small-angle
      neutron scattering with molecular dynamics simulation to characterize the
      structures of full-length wild-type and mutant MerA proteins that mimic the
      system before and during handoff of Hg(2+) from NmerA to the Core. The radii of
      gyration, distance distribution functions, and Kratky plots derived from the
      small-angle X-ray scattering data are consistent with full-length MerA adopting
      elongated conformations as a result of flexibility in the linkers to the NmerA
      domains. The scattering profiles are best reproduced using an ensemble of linker
      conformations. This flexible attachment of NmerA may facilitate fast and
      efficient removal of Hg(2+) from diverse protein substrates. Using a specific
      mutant of MerA allowed the formation of a metal-mediated interaction between
      NmerA and the Core and the determination of the position and relative orientation
      of NmerA to the Core during Hg(2+) handoff.

PMID- 21893071
TI  - Sex ratio dependent dispersal when sex ratios vary between patches.
AB  - Female biased sex ratios reduce competition between brothers when mating takes
      place within local patches. Male dispersal prior to mating is another strategy
      that reduces competition between brothers. One may thus expect these two traits
      to co-evolve and this is partially met in that sex ratios becomes less female
      biased as dispersal increases. However, the evolutionary stable degree of
      dispersal is unaffected by the sex ratio. The analytical models developed to
      reach these conclusions ignored variance in sex ratios, since this increases the
      structural complexity of models. For similar reasons finite clutch sizes are also
      routinely ignored. To overcome these shortfalls, we developed individual based
      simulations that allowed us to incorporate realistic clutch sizes and binomial
      variance in sex ratios between patches. We show that under variable sex ratios,
      males evolve to more readily disperse away from patches with higher sex ratios
      than lower sex ratios. We show that, while the dispersal rate is insensitive to
      the sex ratio when sex ratios are precise, it is affected by the number of males
      with dispersal decreasing as the number of males decreases.

PMID- 21893072
TI  - Exponential transient propagating oscillations in a ring of spiking neurons with
      unidirectional slow inhibitory synaptic coupling.
AB  - Transient oscillations in a ring of spiking neuron models unidirectionally
      coupled with slow inhibitory synapses are studied. There are stable spatially
      fixed steady firing-resting states and unstable symmetric propagating firing
      resting states. In transients, firing-resting patterns rotate in the direction of
      coupling (propagating oscillations), the duration of which increases
      exponentially with the number of neurons (exponential transients). Further, the
      duration of randomly generated transient propagating oscillations is distributed
      in a power law form and spatiotemporal noise of intermediate strength sustains
      propagating oscillations. These properties agree with those of transient
      propagating waves in a ring of sigmoidal neuron models.

PMID- 21893073
TI  - Diepoxybutane induces the formation of DNA-DNA rather than DNA-protein cross
      links, and single-strand breaks and alkali-labile sites in human hepatocyte L02
      cells.
AB  - 1,3-Butadiene (BD) is an air pollutant and a known carcinogen. 1,2,3,4
      Diepoxybutane (DEB), one of the major in vivo metabolites of BD, is considered
      the ultimate culprit of BD mutagenicity/carcinogenicity. DEB is a bifunctional
      alkylating agent, being capable of inducing the formation of monoalkylated DNA
      adducts and DNA cross-links, including DNA-DNA and DNA-protein cross-links (DPC).
      In the present study, we investigated DEB-caused DNA cross-links and breaks in
      human hepatocyte L02 cells using comet assay. With alkaline comet assay, it was
      observed that DNA migration increased with the increase of DEB concentration at
      lower concentrations (10-200MUM); however, at higher concentrations (200
      1000MUM), DNA migration decreased with the increase of DEB concentration. This
      result indicated the presence of cross-links at >200MUM, which was confirmed by
      the co-treatment experiments using the second genotoxic agents, tert-butyl
      hydroperoxide and methyl methanesulfonate. At 200MUM, which appeared as a
      threshold, the DNA migration-retarding effect of cross-links was just observable
      by the co-treatment experiments. At <200MUM, the effect of cross-links was too
      weak to be detected. The DEB-induced cross-links were determined to be DNA-DNA
      ones rather than DPC through incubating the liberated DNA with proteinase K prior
      to unwinding and electrophoresis. However, at the highest DEB concentration
      tested (1000MUM), a small proportion of DPC could be formed. In addition, the
      experiments using neutral and weakly alkaline comet assays showed that DEB did
      not cause double-strand breaks, but did induce single-strand breaks (SSB) and
      alkali-labile sites (ALS). Since SSB and ALS are repaired more rapidly than cross
      links, the results suggested that DNA-DNA cross-links, rather than DPC, were
      probably responsible for mutagenicity/carcinogenicity of DEB.

PMID- 21893074
TI  - An intact medial preoptic area is necessary for zaprinast to modulate paced
      mating behavior in female rats.
AB  - The present study examined the interaction between the regulation of paced mating
      behavior by the medial preoptic area (mPOA) and by the nitric oxide (NO)/cyclic
      guanosine monophosphate (cGMP) pathway, as modulated by zaprinast, a
      phosphodiesterase inhibitor. Rats receiving mPOA or sham lesions were tested for
      paced mating behavior. Subsequently, rats were treated with zaprinast (3 mg/kg)
      before a second paced mating test. The expected lengthening of contact-return
      latencies following intromissions and ejaculations was observed in rats with mPOA
      lesions relative to rats with sham lesions. In addition, rats with sham lesions
      responded to zaprinast with a lengthening of contact-return latency following
      ejaculation. Contact-return latencies did not change in response to zaprinast in
      rats with mPOA lesions. These results demonstrate that the alterations in paced
      mating behavior observed in rats with mPOA lesions persist despite manipulation
      of the nitric oxide-cyclic guanosine monophospate pathway.

PMID- 21893075
TI  - Differential effects of chow and purified diet on the consumption of sucrose
      solution and lard and the development of obesity.
AB  - Obesity has been associated with increased consumption of sweetened beverages and
      a high-fat diet. We determined whether the composition of the dry pellet offered
      with liquid sucrose (LS) and lard influenced the development of obesity. We
      hypothesized that animals offered LS or LS and lard (choice), in addition to chow
      or purified low fat diet pellet (LFD; 10% fat), would gain more body fat than
      controls. We compared the effects of LFD vs. chow on voluntary consumption of LS
      and lard, serum triglyceride (TG), glucose, and body fat over 21 days. Male
      Sprague Dawley rats (n=10/group) were offered chow, chow+LS, chow choice, LFD,
      LFD+LS, LFD choice or solid high-sucrose diet (70% sucrose). Energy intakes of
      rats fed chow, LFD, and high-sucrose diets were similar. Energy intake was
      increased by 16% in chow+LS, 15% in LFD+LS, 11% in LFD choice, and 23% in chow
      choice rats. Chow choice rats consumed 142% more lard than LFD choice rats.
      Fasting glucose increased in all choice rats compared with the chow and high
      sucrose diet rats. Fasting TG increased in LFD choice rats and were ~75% higher
      than those of chow, LFD, or high-sucrose rats. Chow choice had higher carcass fat
      than chow, chow+LS, and LFD groups however LFD choice was not different from
      their controls. Another experiment confirmed rats consumed 158% more lard when
      given chow choice compared to LFD choice. The diet offered to rats with free
      access to LS and lard influenced the development of obesity, sucrose and lard
      selection, and TG.

PMID- 21893076
TI  - Immune cells recruitment and activation by Tityus serrulatus scorpion venom.
AB  - Despite several studies showed that the Tityus serrulatus scorpion venom (Tsv)
      induces an inflammatory response, just a few have investigated the effect of the
      venom on the immune response. Therefore, the aim of this study was to evaluate
      alterations of venom application on lymphoid organs and on the recruitment and
      activation of cells and also on the cytokine production. Swiss male mice (2-3
      months, 20-25 g) received a non-lethal dose of crude Tsv (200 MUg/kg), diluted in
      sterile PBS by subcutaneous route. Control animals received only sterile PBS. The
      animals were sacrificed after 30, 120 and 360 min. The inflammatory parameters
      studied were skin histology at the site of venom application, leukocyte count,
      and blood cytokine levels (IL-6, IL-10, and TNF-alpha). Inguinal lymph node,
      spleen and bone marrow cellularity was determined for evaluation of the Tsv
      effect on immune system organs. The results showed that Tsv caused no local
      inflammation, but it induced an increase of blood neutrophils and serum IL-6, TNF
      alpha and IL-10. After 360 min of envenomation there was a reduction in the cells
      number from peritoneum and spleen, but there was an increase in the cell number
      from lymph nodes. In conclusion, the Tsv induces systemic alterations
      characterized by changes in the cell number in lymphoid organs, increase pro and
      anti-inflammatory cytokines.

PMID- 21893078
TI  - The effect of photopigment optical density on the color vision of the anomalous
      trichromat.
AB  - We present a theoretical model to estimate the influence of photopigment optical
      density (OD) on the color vision of anomalous trichromats. Photopigment spectral
      sensitivities are generated using the Lamb (1995) template, which we correct for
      OD and pre-receptoral filters. Sixteen hyperspectral images (Foster, Nascimento,
      & Amano, 2004; Nascimento, Ferreira, & Foster, 2002) are analyzed, and the
      signals produced in the post-receptoral channels calculated. In the case of
      anomalous trichromats whose two longer-wavelength cones have peak sensitivities
      that lie close together in the spectrum, color vision can be substantially
      enhanced if the cones differ in optical density by a realistic amount.

PMID- 21893077
TI  - Foveal phase retardation changes associated with normal aging.
AB  - This study quantified normal age-related changes to the photoreceptor axons in
      the central macula using the birefringent properties of the Henle fiber layer. A
      scanning laser polarimeter was used to acquire 15 degrees  * 15 degrees  macular
      images in 120 clinically normal subjects, ranging in age from the third decade to
      the eighth. Raw image data of the macular cross were used to compute phase
      retardation maps associated with Henle fiber layer. Annular regions of interest
      ranging from 0.25 degrees  to 3 degrees  eccentricity and centered on the fovea
      were used to generate intensity profiles from the phase retardation data, which
      were then analyzed using sine curve fitting and Fast Fourier Transform (FFT). The
      amplitude of a 2f sine curve was used as a measure of macular phase retardation
      magnitude. For FFT analysis, the 2f amplitude, as well as the 4f, were normalized
      by the remaining FFT components. The amplitude component of the 2f curve fit and
      the normalized 2f FFT component decreased as a function of age, while the
      eccentricity of the maximum value for the normalized 2f FFT component increased.
      The phase retardation changes in the central macula indicate structural
      alterations in the cone photoreceptor axons near the fovea as a function of age.
      These changes result in either fewer cone photoreceptors in the central macula,
      or a change in the orientation of their axons. This large sample size
      demonstrates systematic changes to the central cone photoreceptor morphology
      using scanning laser polarimetry.

PMID- 21893079
TI  - FUdR causes a twofold increase in the lifespan of the mitochondrial mutant gas-1.
AB  - The nematode worm Caenorhabditis elegans has been used to identify hundreds of
      genes that influence longevity and thereby demonstrate the strong influence of
      genetics on lifespan determination. In order to simplify lifespan studies in
      worms, many researchers have employed 5-fluoro-2'-deoxyuridine (FUdR) to inhibit
      the development of progeny. While FUdR has little impact on the lifespan of wild
      type worms, we demonstrate that FUdR causes a dramatic, dose-dependent, twofold
      increase in the lifespan of the mitochondrial mutant gas-1. Thus, the
      concentration of FUdR employed in a lifespan study can determine whether a
      particular strain is long-lived or short-lived compared to wild-type.

PMID- 21893080
TI  - Natural killer cell function is altered during the primary response of aged mice
      to influenza infection.
AB  - Influenza is a public health concern, especially for the elderly. While influenza
      vaccination is efficacious in the young, it offers only limited protection in the
      elderly. Thus, it becomes imperative to understand age-related changes in the
      primary response to influenza infection. This study identified potential age
      related defects in natural killer (NK) cell function during influenza infection.
      We showed that NK cells from aged mice were reduced and had impaired function and
      altered phenotype in lungs during influenza infection. Aged NK cells demonstrated
      decreased IFN-gamma production, but not degranulation, after influenza infection.
      However, after ex vivo activation with YAC-1 cells, aged NK cells demonstrated
      both reduced IFN-gamma production and degranulation. IFN-gamma was also reduced
      in aged NK cells after activation with anti-NKp46 and soluble cytokines. IFN
      beta, and IL-12p40 mRNA expression was not significantly different from that
      observed in adult mice. Analysis of NK cell subsets indicated that aged mice had
      more immature and less terminally mature NK cells. These data suggest that aging
      affects the numbers, function and phenotype of NK cells. Thus, these defects in
      NK cell function could impair the ability of aged mice to induce a strong
      antiviral immune response during the early stages of the infection.

PMID- 21893081
TI  - Mitochondrial dysfunction: a crucial event in okadaic acid (ICV) induced memory
      impairment and apoptotic cell death in rat brain.
AB  - Mitochondrial abnormalities have been identified in a large proportion of
      neurodegenerative diseases. Recently we have reported that
      intracerebroventricular (ICV) administration of okadaic acid (OKA) causes memory
      impairment in rat. However involvement of mitochondrial function in OKA induced
      memory impairment and neuronal damage has not been determined. OKA (200 ng) was
      administered by ICV route. After 13th day of OKA administration memory function
      was evaluated by Morris Water Maze test. Following completion of behavioral
      studies on 16th day, mitochondrial membrane potential, Ca(2+) and reactive oxygen
      species were evaluated in mitochondrial preparation of cortex, hippocampus,
      striatum and cerebellum of rat brain. While ATP, mitochondrial activity, lipid
      peroxidation and nitrite were investigated in synaptosomal preparation of rat
      brain areas. The activities and mRNA expression of apoptotic factors, caspase-3
      and caspase-9, were studied in rat brain regions. The neuronal damage was also
      confirmed by histopathological study. OKA treated rats showed memory impairment
      including increased Ca(2+) and reactive oxygen species and decreased
      mitochondrial membrane potential, ATP and mitochondrial activity in mitochondrial
      preparation. There was a significant increase in lipid peroxidation and nitrite
      in synaptosomal preparations. Preventive treatment daily for 13 days with
      antidementic drugs, donepezil (5 mg/kg, p.o) and memantine (10 mg/kg, p.o),
      significantly attenuated OKA induced mitochondrial dysfunction, apoptotic cell
      death, memory impairment and histological changes. Mitochondrial dysfunction
      appeared as a key factor in OKA induced memory impairment and apoptotic cell
      death. This study indicates that clinically used antidementic drugs are effective
      against OKA induced adverse changes at behavioral, cellular, and histological
      levels and mitochondrial dysfunction.

PMID- 21893082
TI  - Participation of brainstem monoaminergic nuclei in behavioral depression.
AB  - Several lines of research have now suggested the controversial hypothesis that
      the central noradrenergic system acts to exacerbate depression as opposed to
      having an antidepressant function. If correct, lesions of this system should
      increase resistance to depression, which has been partially but weakly supported
      by previous studies. The present study reexamined this question using two more
      recent methods to lesion noradrenergic neurons in mice: intraventricular (ivt)
      administration of either the noradrenergic neurotoxin, DSP4, or of a dopamine
      beta-hydroxylase-saporin immunotoxin (DBH-SAP ITX) prepared for mice. Both agents
      given 2 weeks prior were found to significantly increase resistance to depressive
      behavior in several tests including acute and repeated forced swims, tail
      suspension and endotoxin-induced anhedonia. Both agents also increased locomotor
      activity in the open field. Cell counts of brainstem monoaminergic neurons,
      however, showed that both methods produced only partial lesions of the locus
      coeruleus and also affected the dorsal raphe or ventral tegmental area. Both the
      cell damage and the antidepressant and hyperactive effects of ivt DSP4 were
      prevented by a prior i.p. injection of the NE uptake blocker, reboxetine. The
      results are seen to be consistent with recent pharmacological experiments showing
      that noradrenergic and serotonergic systems function to inhibit active behavior.
      Comparison with previous studies utilizing more complete and selective LC lesions
      suggest that mouse strain, lesion size or involvement of multiple neuronal
      systems are critical variables in the behavioral and affective effects of
      monoaminergic lesions and that antidepressant effects and hyperactivity may be
      more likely to occur if lesions are partial and/or involve multiple monoaminergic
      systems.

PMID- 21893083
TI  - Testosterone as a discriminative stimulus in male rats.
AB  - Testosterone and other anabolic-androgenic steroids (AAS) are reinforcing in
      animals, as determined by conditioned place preference or self-administration.
      Most drugs of abuse produce subjective effects on mood and perception that
      initiate and maintain drug taking. Whether AAS have similar effects is not known.
      Food-restricted male Sprague-Dawley rats (n=9) were tested for their ability to
      discriminate an injection of testosterone from the beta-cyclodextrin vehicle
      using a standard two-lever operant paradigm. In drug discrimination, animals use
      the subjective effects of drug or vehicle to select the appropriate lever to
      obtain food pellets under an FR10 schedule of reinforcement. All rats
      demonstrated vigorous responding for food (1415.1+/-76.1 responses/20 min) with
      94.9% of responses on the active lever. For the first 30 days, rats received
      1mg/kg testosterone sc 30 min before testing. On Day 14, one rat achieved the
      discrimination criteria of 9/10 consecutive days with >90% responses on the
      active lever and <=5 responses on the inactive lever before the first
      reinforcement. Subsequently, rats were tested with testosterone at different
      doses (2, 7.5, 15 mg/kg at 30 min before testing) and times (2mg/kg at 30 or 60
      min before testing), each for 20 days. One additional rat demonstrated successful
      discrimination at Day 54 with 2mg/kg testosterone 60 min before testing. The
      remaining 7 rats failed to discriminate testosterone within 110 days. When
      analyzed according to less-stringent standards, 4 additional rats met criteria
      for testosterone discrimination. However, continued performance was not stable.
      Thus, testosterone was unable to consistently support drug discrimination. We
      conclude that testosterone does not produce rapid interoceptive effects (NIH
      DA12843 to RIW).

PMID- 21893084
TI  - Behavioral and biochemical investigations to explore pharmacological potential of
      PPAR-gamma agonists in vascular dementia of diabetic rats.
AB  - Vascular dementia (VaD) is the second most common dementing illness. We have
      recently reported that diabetes induces VaD in rats. The present study has been
      designed to investigate the potential of peroxisome-proliferator-activated
      receptors-gamma (PPAR-gamma) agonists in diabetes induced VaD of Wistar Albino
      rats. The rats were administered, single dose of streptozotocin (STZ) for the
      induction of diabetes. Morris water-maze (MWM) test was employed for testing
      learning and memory. Serum glucose, bodyweight, vascular endothelial function,
      serum nitrite/nitrate levels, aortic and brain oxidative stress levels (viz.
      aortic superoxide anion levels, brain thiobarbituric acid reactive species and
      brain glutathione levels) and brain acetylcholinesterase activity were also
      tested. STZ treated animals performed poorly on MWM hence reflecting impairment
      of learning and memory behavior with a significant reduction in body weight,
      impairment of vascular endothelial function, and decrease in serum
      nitrite/nitrate levels, increase in serum glucose, aortic and brain oxidative
      stress levels and brain acetylcholinesterase activity. Treatment of PPAR-gamma
      agonists, pioglitazone as well as rosiglitazone significantly reversed, diabetes
      induced impairment of learning and memory behavior, endothelial function, and
      changes in various biochemical parameters. It is concluded that PPAR-gamma
      modulators pioglitazone and rosiglitazone may be considered as potential
      pharmacological agents for the management of diabetes induced VaD.

PMID- 21893085
TI  - Spiritual and religious identities predict the use of complementary and
      alternative medicine among US adults.
AB  - OBJECTIVE: To determine whether spiritual and religious identities predict
      complementary and alternative medicine (CAM) use above and beyond other known
      influences such as gender, region of residence, social status, personality,
      health, and access to conventional medicine. METHODS: Analyzing data from the
      1995-1996 National Survey of Midlife Development in the United States (n=3032),
      this study examines the correlations between four aspects of
      spirituality/religiousness-i.e., spiritual only, religious only, both spiritual
      and religious, and neither spiritual nor religious-and six measures of CAM.
      RESULTS: Compared with spiritual only persons, the odds of using energy therapies
      are 86% lower for spiritual and religious persons, 65% lower for religious only
      persons, and 52% lower for neither spiritual nor religious persons. Compared to
      spiritual only persons, spiritual and religious individuals are 43% more likely
      to use body-mind therapies in general; however, when this category does not
      contain prayer, meditation, or spiritual healing, they are 44% less likely.
      Religious only individuals are disinclined toward CAM use. CONCLUSIONS: After
      controlling for established predictors including educational attainment,
      personality, social support, and access to conventional medicine, the present
      study demonstrates that spirituality and religiousness are associated, in unique
      ways, with CAM use. Additional research on this topic is clearly warranted.

PMID- 21893086
TI  - Multiple health behaviors and serum hepatic enzymes among US adults with obesity.
AB  - INTRODUCTION: This study was to examine the cumulative number and clustering
      patterns of low-risk health behaviors (i.e., not currently smoking, not excessive
      drinking, and physically active) associated with elevation of serum alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), and gamma
      glutamyltransferase (GGT) among adults with obesity in the United States.
      METHODS: We estimated the age-adjusted prevalence of elevated ALT, AST, and GGT
      from 4547 adults with obesity aged >= 20 years who participated in the 2005-2008
      National Health and Nutrition Examination Survey. The associations between the
      cumulative number or clustering patterns of low-risk health behaviors and
      measures of serum ALT, AST, and GGT were assessed using multivariate regression
      models. RESULTS: Adult men who reported having three low-risk health behaviors
      were 62%, 39%, and 48% less likely to have elevated serum ALT, AST, and GGT,
      respectively; adult women were 56% and 73% less likely to have elevated serum AST
      and GGT, respectively, when compared to their respective counterparts who
      reported having none of the low-risk health behaviors. CONCLUSIONS: The findings
      of this study indicate that, among adults with obesity, having multiple low-risk
      health behaviors is associated with decreased likelihoods of elevated hepatic
      enzymes, including ALT in men, AST and GGT in both men and women.

PMID- 21893087
TI  - Purification and physicochemical properties of different polysaccharide fractions
      from the water extract of Boschniakia rossica and their effect on macrophages
      activation.
AB  - Today more and more attentions had been attracted by many nutritionists and
      pharmacologists on polysaccharides from natural plants or animals due to their
      significant biological activities. In this research three polysaccharides (BRR
      W1, BRR-WA1 and BRR-WA2) were isolated and purified from the water extract of
      Boschniakia rossica by DEAE Sepharose Fast Flow and Sepharose 6 Fast Flow column
      chromatography. Chemical and physical characteristics of three polysaccharides
      were investigated by a combination of chemical and instrumental analysis methods.
      The assays of their effect on macrophages activation were also investigated in
      vitro, including phagocytosis of macrophages, detections for NO production and
      TNF-alpha secretion. The results indicated that the effect of polysaccharides on
      macrophages activation was influenced by their respective physicochemical
      properties.

PMID- 21893088
TI  - A facile method for preparing biodegradable chitosan derivatives with low
      grafting degree of poly(lactic acid).
AB  - Chemical modification of chitosan by grafting with PLA (CS-g-PLA) was developed
      via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) mediated coupling
      reaction. The introduction of PLA disrupted the crystalline structure of
      chitosan, improved its solubility and thermal stability. Low degree of PLA
      substitution showed better degradation efficiency than chitosan and PLA. Weight
      loss of CS-g-PLA6 and CS-g-PLA4 was 87% and 94%, respectively, in 7 days
      enzymatic degradation study. CS-g-PLA2 was totally degraded in 1 day. Self
      assembly behavior was studied using pyrene fluorescence dye technique and found
      to be PLA grafting level dependent. CS-g-PLA with low grafting degree showed
      hydrophilic, self-assembling properties and controllable biodegradability that
      may widen its applications.

PMID- 21893090
TI  - Thermal unfolding of apo- and holo-enolase from Saccharomyces cerevisiae:
      different mechanisms, similar activation enthalpies.
AB  - Yeast enolase is stabilized by its natural cofactor Mg(2+). This stabilization is
      ascribed to the reduced subunit dissociation of the holoprotein. Nevertheless,
      how Mg(2+) alters the unfolding mechanism has yet to be fully characterized.
      Here, we investigate the role of Mg(2+) in the denaturation mechanism and
      unfolding kinetics of yeast enolase. Apo-enolase unfolds through a three-state
      process (N(2)<->2I->2D). The intermediate species is described as a monomeric
      molten globule-like conformation that becomes noticeable in the presence of
      phosphate and is able to recover its native secondary structure when cooled down.
      Kinetic studies confirmed the presence of the intermediate species, even though
      it was not noticeable in the thermal scans. The cofactor increases the
      cooperativity of the unfolding transitions, while the intermediate species
      becomes less noticeable or nonexistent. Thus, holo-enolase follows a simple two
      state mechanism (N(2)->2D). Our results indicate smaller unfolding rate-constants
      in the presence of Mg(2+), thus favoring the native state. The temperature
      dependence of the unfolding rates allowed us to calculate the activation
      enthalpies of denaturation. Interestingly, despite the different unfolding
      mechanisms of the apo and holo forms of enolase, they both have similar
      activation barriers of denaturation (185-190 kJ mol(-1)).

PMID- 21893089
TI  - Synthesized oversulfated and acetylated derivatives of polysaccharide extracted
      from Enteromorpha linza and their potential antioxidant activity.
AB  - Sulfated polysaccharide extracted from blue algae Enteromorpha linza is proved to
      possess excellent antioxidant activities. Two derivatives by means of
      oversulfated and acetylated coupling were synthesized and investigated their
      antioxidant activities including scavenging effect of superoxide, hydroxyl and
      1,1-diphenyl-2-picrylhydrazyl radicals. And then the relationship between
      antioxidant activity and chemical characteristics was characterized. The results
      of chemical analysis and FT-IR showed that the modification of polysaccharide was
      successful. In addition, it was found that certain derivatives exhibited stronger
      antioxidant activity than raw material. They could serve as free-radical
      inhibitors or scavengers, acting possibly as primary antioxidants.

PMID- 21893091
TI  - Immune responses elicited in rainbow trout through the administration of
      infectious pancreatic necrosis virus-like particles.
AB  - Virus like particles (VLPs) against viral pathogens not only constitute a novel
      approach for the development of antiviral vaccines for an specific virus, but
      also for the creation of multivalent vaccines in which antigens from other
      pathogens may be expressed on the surface of these VLPs. Despite positive results
      on protection for many of these VLPs in both fish and mammals, not many studies
      have focused on the immune response triggered by these particles; studies that
      may provide hints for the identification of immune mechanisms responsible for
      antiviral protection, which are mostly unknown in fish. In the current work, we
      have studied the levels of transcription of several immune genes in the spleen of
      rainbow trout (Oncorhynchus mykiss) intraperitoneally injected with VLPs from
      infectious pancreatic necrosis virus (IPNV) focusing on the chemokine response as
      well as the response of genes related to interferon (IFN) production.
      Surprisingly, the capacity of VLPs to induce chemokines differed from that of
      live IPNV, suggesting a direct effect of viral replication on the chemokine
      response in this organ. While VLPs up-regulated the transcription of CK3, CK10
      and CXCd and down-modulated CK5B, CK6 and CK9 transcription, a previous study in
      which the transcription of gammaIP, CXCd, CK1, CK3, CK5B, CK6, CK7A, CK9 and CK12
      had been studied demonstrated that IPNV only significantly up-regulated CK6 and
      down-modulated CK3 in the spleen. On the other hand, the administration of VLPs
      produced a strong mobilization to the peritoneum of CD4(+), IgM(+), IgT(+) and
      CD83(+) leukocytes similar to that induced by the live viral infection. In both
      cases, this leukocyte recruitment seemed to be greatly mediated through CK3,
      CK5B, CK9 and CK10 chemokine production. These results together with the fact
      that VLPs strongly induced non-specific lymphocyte proliferation and specific
      anti-IPNV antibody production point to VLPs as excellent candidates for vaccine
      development.

PMID- 21893092
TI  - A novel pathogen-binding gC1qR homolog, FcgC1qR, in the Chinese white shrimp,
      Fenneropenaeus chinensis.
AB  - In vertebrates, the globular "head" of complement component C1q receptor (gC1qR)
      is a versatile, multiligand binding protein. However, research on its function in
      invertebrates is limited. In the present study, a full-length cDNA sequence of a
      novel gC1qR homolog, FcgC1qR, from the Chinese white shrimp Fenneropenaeus
      chinensis was cloned. Semi-quantitative polymerase chain reaction (PCR) detected
      FcgC1qR in all examined tissues, with the highest level detected in the
      intestine. Western blot assay further revealed that the FcgC1qR protein was
      distributed in all tested tissues except the cell-free hemolymph of normal
      Chinese white shrimp. In the expression pattern study, quantitative real-time PCR
      demonstrated that the transcripts of FcgC1qR were up-regulated when challenged
      with bacteria (Vibrio anguillarum or Staphylococcus aureus) and white spot
      syndrome virus. Subsequently, FcgC1qR was over-expressed in Escherichia coli, and
      the polyclonal antibody was prepared with the purified recombinant protein.
      Microorganism binding was examined using Western blot assay, and revealed that
      FcgC1qR could bind to Bacillus cereus, Bacillus thuringiensis, S. aureus, V.
      anguillarum, Vibrioharveyi, and Candida albicans. FcgC1qR was also proven able to
      bind to S. aureus in a concentration-dependent manner, and this binding activity
      was partly inhibited by the polyclonal antibody. These results suggest that
      FcgC1qR may be involved in defending against bacterial infections in the Chinese
      white shrimp.

PMID- 21893093
TI  - The pharmacological importance of agmatine in the brain.
AB  - Agmatine is a polyamine that is produced via decarboxylation of l-arginine by the
      enzyme arginine decarboxylase. It binds to various receptors and has been
      accepted as a novel neurotransmitter in brain. In experimental studies, agmatine
      exhibited anticonvulsant, antinociceptive, anxiolytic and antidepressant-like
      actions. Furthermore, it has some beneficial effects on cerebral ischemia models
      in animals. Agmatine interacts with the mechanisms of withdrawal syndromes for
      several addictive agents. It also modulates some processes involved in learning
      and memory. Thus, agmatine seems to be a valuable agent for the treatment of
      behavioral and neurodegenerative disorders. However, the aberrant release and
      transmission of agmatine in the central nervous system (CNS) may be associated
      with mechanisms of several CNS disorders, such as psychosis. Interactions between
      agmatine and other central neurotransmitter systems, such as the glutamatergic
      and nitrergic systems, are also very important. In light of the current
      literature on agmatine, we can anticipate that the central agmatinergic system
      may be an important target in development of novel strategies and approaches for
      understanding the etiopathogenesis of some important central disorders and their
      pharmacological treatments. The main objective of this review is to investigate
      and update the information on effects of agmatine in CNS and highlight its
      pharmacological importance in central disorders.

PMID- 21893094
TI  - Pharmacotherapy for traumatic brain injury: focus on sympathomimetics.
AB  - Traumatic brain injury (TBI) is a devastating neurological injury with broad
      manifestations. Unfortunately, its diagnosis and efficacious treatments remain
      elusive. Different post injury symptoms are exhibited at different time frames,
      indicative of a time-related progression of the pathology. Therefore, particular
      treatments must be tailored to the post injury time frame. This overview is
      focused on the secondary chronic phase following TBI and the value of
      sympathomimetic therapy during this phase. The various direct- and indirect
      acting drugs are reviewed, and the treatment protocol employed by the author is
      described.

PMID- 21893095
TI  - Microcontroller based fibre-optic visual presentation system for multisensory
      neuroimaging.
AB  - Presenting visual stimuli in physical 3D space during fMRI experiments carries
      significant technical challenges. Certain types of multisensory visuotactile
      experiments and visuomotor tasks require presentation of visual stimuli in
      peripersonal space, which cannot be accommodated by ordinary projection screens
      or binocular goggles. However, light points produced by a group of LEDs can be
      transmitted through fibre-optic cables and positioned anywhere inside the MRI
      scanner. Here we describe the design and implementation of a microcontroller
      based programmable digital device for controlling fibre-optically transmitted LED
      lights from a PC. The main feature of this device is the ability to independently
      control the colour, brightness, and timing of each LED. Moreover, the device was
      designed in a modular and extensible way, which enables easy adaptation for
      various experimental paradigms. The device was tested and validated in three fMRI
      experiments involving basic visual perception, a simple colour discrimination
      task, and a blocked multisensory visuo-tactile task. The results revealed
      significant lateralized activation in occipital cortex of all participants, a
      reliable response in ventral occipital areas to colour stimuli elicited by the
      device, and strong activations in multisensory brain regions in the multisensory
      task. Overall, these findings confirm the suitability of this device for
      presenting complex fibre-optic visual and cross-modal stimuli inside the scanner.

PMID- 21893096
TI  - Effective inhibition of a Strongylocentrotus nudus eggs polysaccharide against
      hepatocellular carcinoma is mediated via immunoregulation in vivo.
AB  - This study was aimed at evaluating the inhibitory effect of a polysaccharide that
      was isolated from Strongylocentrotus nudus eggs (SEP) against hepatocellular
      carcinoma in H22-bearing mice and elucidating its immunological mechanisms by
      determining its effects on the growth of transplanted tumors and immune response
      in H22-bearing mice. ICR mice inoculated with mouse hepatoma carcinoma cell lines
      H22 were treated with SEP at doses of 4, 8, 16 mg/kg/d for 12 days. The effects
      of SEP were measured via the growth of the transplanted tumors, splenocyte
      proliferation, T lymphocytes counts, CTL activity, the production of cytokines
      from splenocytes and the levels of serum Ig in tumor-bearing mice. In addition,
      the effects of SEP on Erk phosphorylation in mouse splenocytes and on the
      transcriptional activity of NFAT in Jurkat T cells were also investigated. Our
      results showed that SEP significantly inhibited the growth of transplanted tumors
      in mice. SEP could not only remarkably enhance splenocyte proliferation, CD4(+)
      and CD8(+) T cell numbers as well as CTL activity, but it also elevated IL-2 and
      TNF-alpha secretion as well as IgA, IgM and IgG levels in the serum. Furthermore,
      the activation of Erk phosphorylation and the NFAT promoter by SEP promoted the
      transcription and expression of downstream gene IL-2. In conclusion, our study
      demonstrates that SEP effectively inhibits hepatocellular carcinoma in vivo via
      enhancement of host immune system function, and it could be a potential
      therapeutic drug for hepatocarcinoma.

PMID- 21893097
TI  - Blue native protein electrophoresis for studies of mouse polyomavirus
      morphogenesis and interactions between the major capsid protein VP1 and cellular
      proteins.
AB  - Morphogenesis of the mouse polyomavirus virion is a complex and not yet well
      understood process. Nuclear lysates of infected cells and cells transiently
      producing the major capsid protein (VP1) of the mouse polyomavirus and whole-cell
      lysates were separated by blue native polyacrylamide gel electrophoresis (BN
      PAGE) to characterize the participation of cellular proteins in virion precursor
      complexes. Several VP1-specific complexes were found by immunostaining with the
      anti-VP1 antibody. Some of these complexes contained proteins from the heat shock
      protein 70 family. The BN-PAGE was found to be a useful tool for the
      identification of protein complexes by immunostaining of separated cell lysates.
      However, whole-cell lysates and lysates of isolated nuclei of cells infected with
      polyomavirus appeared to be too complex for BN-PAGE separation followed by mass
      spectrometry. No distinct bands specific for cells infected with polyomavirus
      were detected by Coomassie blue stained gels, hence this method is not suitable
      for the discovery of new cellular proteins participating in virion assembly.
      Nevertheless, BN-PAGE can be valuable for the analyses of different types of
      complexes formed by proteins after their enrichment or isolation by affinity
      chromatography.

PMID- 21893098
TI  - A DNA-based West Nile virus replicon elicits humoral and cellular immune
      responses in mice.
AB  - While self-replicating, non-infectious subgenomic flavivirus replicons have been
      described, most of them are RNA transcripts under the control of an Sp6 or T7
      promoter. In this study, using West Nile virus (WNV) as a model, a series of DNA
      based reporter replicons under the control of a minimal cytomegalovirus (CMV)
      immediate-early promoter were constructed, and functional analysis showed that
      these reporter replicons replicate efficiently in mammalian cells. When the DNA
      based WNV replicon was used to immunize mice, NS1-specific IgG antibodies and
      anti-WNV neutralizing antibodies were both induced. Additionally, immunization
      with this DNA-based WNV replicon induced high levels of lymphocyte proliferation
      and enhanced the secretion of IFN-gamma. These results suggest that this type of
      DNA-based replicon can induce humoral and cellular immune responses in mice,
      indicating that this type of DNA-based replicon may serve as a useful platform
      for vaccine development and protein expression.

PMID- 21893099
TI  - Enhanced expression of secretable influenza virus neuraminidase in suspension
      mammalian cells by influenza virus nonstructural protein 1.
AB  - Influenza neuraminidase (NA) is a major target for anti-influenza drugs. With an
      increasing number of viruses resistant to the anti-NA drug oseltamivir,
      functionally active recombinant NA is needed for screening novel anti-NA
      compounds. In this study, the secretable NA (sNA) head domain of influenza
      A/Vietnam/DT-036/05 (H5N1) virus was expressed successfully in human embryonic
      kidney (HEK-293T) cells and shown to be enzymatically active. The inclusion of a
      plasmid encoding nonstructural protein 1 (NS1) of influenza A/Puerto Rico/8/34
      virus with the sNA plasmid in the cotransfection demonstrated an increase in H5N1
      sNA expression by 7.4 fold. Subsequently, the sNA/NS1 cotransfection protocol in
      serum-free 293-F suspension cell culture was optimized to develop a rapid
      transient gene expression (TGE) system for expression of large amounts of H5N1
      sNA. Under optimized conditions, NS1 enhanced H5N1 sNA expression by 4.2 fold.
      The resulting H5N1 sNA displayed comparable molecular weight, glycosylation, K(m)
      for MUNANA, and K(i) for oseltamivir carboxylate to those of H5N1 NA on the virus
      surface. Taken together, the NS1-enhancing sNA expression strategy presented in
      this study could be used for rapid high-level expression of enzymatically active
      H5N1 sNA in suspension mammalian cells. This strategy may be applied for
      expression of sNA of other strains of influenza virus as well as the other
      recombinant proteins.

PMID- 21893100
TI  - An attenuated EIAV vaccine strain induces significantly different immune
      responses from its pathogenic parental strain although with similar in vivo
      replication pattern.
AB  - The EIAV (equine infectious anemia virus) multi-species attenuated vaccine
      EIAV(DLV121) successfully prevented the spread of equine infectious anemia (EIA)
      in China in the 1970s and provided an excellent model for the study of protective
      immunity to lentiviruses. In this study, we compared immune responses induced by
      EIAV(DLV121) to immunity elicited by the virulent EIAV(LN40) strain and
      correlated immune responses to protection from infection. Horses were randomly
      grouped and inoculated with either EIAV(DLV121) (Vaccinees, Vac) or a sublethal
      dose of EIAV(LN40) (asymptomatic carriers, Car). Car horses became EIAV(LN40)
      carriers without disease symptoms. Two of the four Vac horses were protected
      against infection and the other two had delayed onset or reduced severity of EIA
      with a lethal EIAV(LN40) challenge 5.5 months post initial inoculation. In
      contrast, all three Car animals developed acute EIA and two succumbed to death.
      Specific humoral and cellular immune responses in both Vac and Car groups were
      evaluated for potential correlations with protection. These analyses revealed
      that although plasma viral loads remained between 10(3) and 10(5)copies/ml for
      both groups before EIAV(LN40) challenge, Vac-treated animals developed
      significantly higher levels of conformational dependent, Env-specific antibody,
      neutralizing antibody as well as significantly elevated CD4(+) T cell
      proliferation and IFN-gamma-secreting CD8(+) T cells than those observed in
      EIAV(LN40) asymptomatic carriers. Further analysis of protected and unprotected
      cases in vaccinated horses identified that cellular response parameters and the
      reciprocal anti-p26-specific antibody titers closely correlated with protection
      against infection with the pathogenic EIAV(LN40). These data provide a better
      understanding of protective immunity to lentiviruses.

PMID- 21893101
TI  - Virostatic potential of micro-nano filopodia-like ZnO structures against herpes
      simplex virus-1.
AB  - Herpes simplex virus type-1 (HSV-1) entry into target cell is initiated by the
      ionic interactions between positively charged viral envelop glycoproteins and a
      negatively charged cell surface heparan sulfate (HS). This first step involves
      the induction of HS-rich filopodia-like structures on the cell surface that
      facilitate viral transport during cell entry. Targeting this initial first step
      in HSV-1 pathogenesis, we generated different zinc oxide (ZnO) micro-nano
      structures (MNSs) that were capped with multiple nanoscopic spikes mimicking cell
      induced filopodia. These MNSs were predicted to target the virus to compete for
      its binding to cellular HS through their partially negatively charged oxygen
      vacancies on their nanoscopic spikes, to affect viral entry and subsequent
      spread. Our results demonstrate that the partially negatively charged ZnO-MNSs
      efficiently trap the virions via a novel virostatic mechanism rendering them
      unable to enter into human corneal fibroblasts - a natural target cell for HSV-1
      infection. The anti-HSV-1 activity of ZnO MNSs was drastically enhanced after
      creating additional oxygen vacancies under UV-light illumination. Our results
      provide a novel insight into the significance of ZnO MNSs as the potent HSV-1
      inhibitor and rationalize their development as a novel topical agent for the
      prevention of HSV-1 infection.

PMID- 21893102
TI  - Developmentally degraded directional selectivity of the auditory cortex can be
      restored by auditory discrimination training in adults.
AB  - Sound localization is one of the most important tasks performed by the auditory
      system. Studies have shown that intensive training can remediate deteriorated
      frequency representations and temporal information processing in the adult
      primary auditory cortex (A1) induced by early post-natal pulsed noise exposure.
      Here we demonstrate that intensive sound location discrimination training
      improved the dysfunctional sound azimuth selectivity degraded by early post-natal
      pulsed noise exposure. Rats exposed to pulsed white noise during a post-natal
      critical period were successfully trained to identify a target sound stimulus
      with specific azimuth angle that changed daily on a random schedule. Consistent
      with recovery of behavioral accuracy for sound-azimuth discriminations, we found
      that the average angular range (AR) of A1 neuronal azimuth selective curves in
      trained noise-raised rats was not significantly different from that measured in
      control rats, while the average AR of A1 neurons in untrained noise-raised rats
      was significantly higher, indicating that these neurons were less direction
      selective. Directional selectivity of A1 neurons was normalized by training, thus
      demonstrating the benefits of sensory discrimination training as a strategy for
      restoring auditory function in adult mammals damaged by sensory disruption during
      critical periods of cortical development.

PMID- 21893103
TI  - The influence of neonatal serotonin depletion on emotional and exploratory
      behaviours in rats.
AB  - Recent studies have shown that neurodevelopmental disturbances in the structure
      and function of the brain are significant factors in the onset of psychiatric
      disorders. Such deficits may also affect neurotransmission. Among the different
      neurotransmitter systems, serotonin (5-HT) plays an important role in the
      organisation and maturation of brain structures during development. The aim of
      the present study was to examine the influence of neonatal 5-HT depletion on
      emotional and exploratory behaviours in adult rats. Three-day-old Wistar male
      rats received intraventricular injections of the selective serotonin neurotoxin
      5,7-dihydroxytryptamine (5,7-DHT). Littermates given saline injections acted as
      controls. After three months, rat behaviour was analysed in an open field test, a
      social interaction test and a novel object test. Moreover, contextual-conditioned
      freezing and ultravocalisation fear responses were studied. The pain reactivity
      was measured in a flinch-jump test. Biochemical analysis of 5,7-DHT-treated rats
      revealed a significant decrease in the concentration of 5-HT and its metabolite
      in the frontal cortex, hippocampus and striatum, with a decreased dopamine level
      in striatum. Early serotonin depletion reduced locomotor activity in the open
      field test and attenuated social interaction in non-aversive conditions and
      exploration of a novel object in adult rats. Ultravocalisation, but not freezing,
      was increased in the contextual fear-conditioning paradigm in 5-HT-depleted rats.
      There was no difference in the pain threshold between groups. These data
      demonstrate that neonatal 5-HT depletion resulted in subtle alterations in the
      locomotor, exploratory and conditioned fear response of adult animals.

PMID- 21893104
TI  - Adult neurogenesis. From circuits to models.
AB  - Our understanding of the hippocampus as a memory-encoding device is greatly
      helped by our knowledge of neuronal circuits and their plasticity. The
      trisynaptic hippocampal circuit carrying afferent input from the entorhinal
      cortex, controlled by a network of inhibitory interneurons and supplemented by
      modulatory subcortical inputs forms a platform for multiple forms of synaptic
      plastic mechanisms. Long-term potentiation of synaptic transmission in its
      various forms is an outstanding example of hippocampal ability to adapt to past
      neuronal activity. Adult neurogenesis is a profound plastic mechanism
      incorporating structural and functional changes that were previously thought to
      be present only in developing neural systems. These powerful forms of plasticity
      can mask experimental results by compensating for experimentally induced changes
      in the neurons or circuits. Circuit lesions have been one of the most common
      techniques in scientific investigations of the hippocampus. Although the effects
      of such lesions can be quite revealing and ground-breaking, in many cases the
      results are masked by compensatory mechanisms producing misleading results. This
      review will highlight such mechanisms and argue that the experimental results, in
      spite of their shortcomings, can be better understood when viewed in light of our
      knowledge of the neuronal circuitry, and with guidance by conceptual and
      computational models. Studies demonstrating a role of neurogenesis in pattern
      separation and memory interference are a good example of fruitful interaction
      between modeling and experimental approaches.

PMID- 21893106
TI  - Design and characterization of a fluorescent ghrelin analog for imaging the
      growth hormone secretagogue receptor 1a.
AB  - Ghrelin is a 28-amino acid peptide hormone produced in the stomach. It binds to
      the growth hormone secretagogue receptor 1a (GHS-R1a), a class A G-protein
      coupled receptor. In the present study, we describe the design, synthesis and
      characterization of a truncated, 18-amino acid analog of ghrelin conjugated to a
      fluorescent molecule, fluorocein isothiocyanate (FITC), through the addition of a
      lysine at its C terminus ([Dpr(octanoyl)(3), Lys(fluorescein)(19)]ghrelin(1-19)).
      Receptor binding affinity of this novel fluorescein-ghrelin(1-18) was similar to
      that of wild-type ghrelin and a synthetic GHS-R1a ligand, hexarelin. Live cell
      imaging in CHO/GHS-R1a cells demonstrated cell surface receptor labeling and
      internalization, and agonist activity of fluorescein-ghrelin(1-18) was confirmed
      by increased phosphorylation of ERK1/2. We also show that GHS-R1a protein is
      expressed primarily in the heart when compared to all other organs, suggesting
      high receptor density in the left ventricle. Finally, we demonstrate that
      fluorescein-ghrelin(1-18) binds specifically to heart tissue in situ, and its
      binding is displaced by both wt ghrelin and hexarelin. We have therefore
      developed a novel imaging probe, fluorescein-ghrelin(1-18), that can be used to
      image GHS-R1a in situ, for the purposes of investigating mechanisms of receptor
      trafficking or pharmacological agents that target GHS-R1a.

PMID- 21893105
TI  - TsAg5, a Taenia solium cysticercus protein with a marginal trypsin-like activity
      in the diagnosis of human neurocysticercosis.
AB  - Neurocysticercosis is an endemic parasitic disease caused by Taenia solium larva.
      Although the mechanism of infection is not completely understood, it is likely
      driven by proteolytic activity that degrades the intestinal wall to facilitate
      oncosphere penetration and further infection. We analyzed the publicly available
      T. solium EST/DNA library and identified two contigs comprising a full-length
      cDNA fragment very similar to Echinococcus granulosus Ag5 protein. The T. solium
      cDNA sequence included a proteolytic trypsin-like-domain in the C-terminal
      region, and a thrombospondin type-1 adherence-domain in the N-terminal region.
      Both the trypsin-like and adherence domains were expressed independently as
      recombinant proteins in bacterial systems. TsAg5 showed marginal trypsin-like
      activity and high sequence similarity to Ag5. The purified antigens were tested
      in a Western immunoblot assay to diagnose human neurocysticercosis. The
      sensitivity of the trypsin-like-domain was 96.36% in patients infected with
      extraparenchymal cysts, 75.44% in patients infected with multiple cysts, and
      39.62% in patients with a single cyst. Specificity was 76.70%. The thrombospondin
      type-1 adherence-domain was not specific for neurocysticercosis.

PMID- 21893107
TI  - Enumerating bacterial cells on bioadhesive coated slides.
AB  - Quantifying bacterial abundance and biomass is fundamental to many
      microbiological studies. Directly counting via epifluorescence microscopy has
      become the method of choice, especially for environmental samples, and
      conventional techniques require filtration of cells onto black polycarbonate
      membrane filters. We investigated the utility of instead capturing stained
      bacterial suspensions on bioadhesive slides, performing tests using pure cultures
      of bacteria, mixtures of cultured bacteria, and environmental samples from five
      habitat types. When compared to the standard filtration and flow cytometric
      approaches, bioadhesive slides were found to be an accurate and precise platform
      for rapid enumeration of bacteria. Total bacterial counts made using the three
      methods were positively correlated for acridine orange and Live/Dead(r) (L/D)
      staining (0.81<=r<=0.95, all p<=0.002). All platforms had similar precision,
      though counts obtained using bioadhesive slides were significantly higher than
      those made with polycarbonate filters and flow cytometry. The specific
      bioadhesive slides we used resulted in substantial cell mortality for certain
      pure cultures and river water samples, limiting their use for L/D determination.
      Cell enumeration using bioadhesive slides is particularly effective because it is
      highly precise at a wide range of cell concentrations, allows observation of
      cells that are not readily discernible on filters, reduces the number of steps
      and processing materials associated with sample analysis, and increases
      throughput.

PMID- 21893108
TI  - The observer observed: frontal EEG asymmetry and autonomic responses
      differentiate between another person's direct and averted gaze when the face is
      seen live.
AB  - Recently, we showed that another person's gaze direction influenced the
      perceiver's frontal EEG asymmetry and autonomic arousal in response to freely
      viewed real faces, but not in response to face pictures. However, the lack of a
      task during the viewing may have resulted in less attention allocation to face
      pictures vs. live faces. In the present study, the participants performed two
      online tasks while viewing the faces presented live through an electronic shutter
      and as pictures on a computer screen. The results replicated those from our
      previous experiment showing that direct gaze elicited greater relative left-sided
      frontal EEG asymmetry and autonomic arousal than averted gaze but, again, only in
      the live condition. However, the results also showed that two live stimulus faces
      (male and female) elicited differential EEG asymmetry responses in our
      participants (all females), and the effects of gaze direction were observed only
      for the (live) female faces. The results suggest that the discriminative
      responses to live faces vs. pictures are likely to reflect the participants'
      enhanced mental-state attributions and self-awareness when looking at and being
      looked by live faces. Thus, the motivation- and affect-related
      psychophysiological responses to gaze direction are most discriminative in the
      presence of another person, regardless of whether the face/gaze is actively
      monitored or not.

PMID- 21893109
TI  - An event-related potential study of semantic style-match judgments of artistic
      furniture.
AB  - This study investigates how semantic networks represent different artistic
      furniture. Event-related potentials (ERPs) were recorded while participants made
      style-match judgments for table and chair sets. All of the tables were in the
      Normal style, whereas the chairs were in the Normal, Minimal, ReadyMade, or
      Deconstruction styles. The Normal and Minimal chairs had the same rates of
      "match" responses, which were both higher than the rates for the ReadyMade and
      Deconstruction chairs. Compared with Normal chairs, the ERPs elicited by both
      ReadyMade chairs and Deconstruction chairs exhibited reliable N400 effects, which
      suggests that these two design styles were unlike the Normal design style.
      However, Minimal chairs evoked ERPs that were similar to the ERPs of Normal
      chairs. Furthermore, the N400 effects elicited by ReadyMade and Deconstruction
      chairs showed different scalp distributions. These findings reveal that semantic
      networks represent different design styles for items of the same category.

PMID- 21893110
TI  - Ultra-high olfactory sensitivity for the human sperm-attractant aromatic aldehyde
      bourgeonal in CD-1 mice.
AB  - Recent studies have shown that certain aromatic aldehydes are ligands for
      olfactory receptors expressed in mammalian sperm cells and induce sperm
      chemotaxis. Using a conditioning paradigm, the olfactory sensitivity of five CD-1
      mice for seven aromatic aldehydes was investigated. With all seven stimuli, the
      mice discriminated concentrations as low as 0.01 ppm (parts per million) from the
      solvent, and with bourgeonal the animals even detected concentrations as low as
      0.1 ppq (parts per quadrillion) which constitutes the lowest olfactory detection
      threshold value reported in this species so far. The presence of a tertiary butyl
      group in para-position (relative to the functional aldehyde group) combined with
      a lack of an additional alkyl group next to the functional aldehyde group may be
      responsible for the extraordinary sensitivity of the mice for bourgeonal.

PMID- 21893111
TI  - Effects of antipsychotic drugs on BDNF, GSK-3beta, and beta-catenin expression in
      rats subjected to immobilization stress.
AB  - Brain-derived neurotrophic factor (BDNF), glycogen synthase kinase-3beta (GSK
      3beta), and beta-catenin have been reported to be altered in patients with
      schizophrenia and have been targeted by antipsychotic drugs. Atypical
      antipsychotics, but not typical antipsychotics, exert neuroprotective effects by
      regulating these proteins. In this study, we analyzed the effects of the atypical
      antipsychotic drugs olanzapine and aripiprazole and a typical antipsychotic drug,
      haloperidol, on the expression of BDNF, phosphorylated GSK-3beta, and beta
      catenin in the hippocampus of rats subjected to immobilization stress. Rats were
      subjected to immobilization stress 6h/day for 3 weeks. The effects of olanzapine
      (2 mg/kg), aripiprazole (1.5 mg/kg), and haloperidol (1.0 mg/kg) were determined
      on BDNF, serine9-phosphorylated GSK-3beta, and beta-catenin expression by Western
      blotting. Immobilization stress significantly decreased the expression of BDNF,
      phosphorylated GSK-3beta, and beta-catenin in the hippocampus. Chronic
      administration of olanzapine and aripiprazole significantly attenuated the
      decreased expression of these proteins in the hippocampus of rats caused by
      immobilization stress, and significantly increased the levels of these proteins
      even without the immobilization stress. However, chronic haloperidol had no such
      effect. These results suggest that olanzapine and aripiprazole may exert
      beneficial effects by upregulating BDNF, phosphorylated GSK-3beta, and beta
      catenin in patients with schizophrenia.

PMID- 21893112
TI  - The relationship between callosal axons and cortical neurons in the planum
      temporale: alterations in schizophrenia.
AB  - The relationship between "connectivity" measures such as DTI and the cellular
      alterations in the cortex that give rise to those connections remains unclear.
      Cytoarchitectural changes in the planum temporale (PT) suggest impaired layer III
      feedforward projection neurons in schizophrenia. Altered hemispheric asymmetry of
      the PT has been reported in patients, along with altered white matter density in
      the corpus callosum, and there is anomalous activation of the PT during auditory
      hallucinations. We measured layer III cell density and pyramidal neuron size in
      PT of both hemispheres of post-mortem brains from patients with schizophrenia
      (n=16) and control subjects (n=16). We found reduced cell density and the loss of
      a correlation between magnopyramidal neuron density and axon number in the
      isthmus of the corpus callosum in schizophrenia. The normal asymmetry indicated
      that magnopyramidal neurons tend towards being larger and denser in the left PT
      but this asymmetry is significantly reduced in schizophrenia. The findings offer
      cytoarchitectural insight into the relationship between PT cortex and callosal
      white matter abnormalities in schizophrenia.

PMID- 21893113
TI  - Enhancement of the skin-protective activities of Centella asiatica L. Urban by a
      nano-encapsulation process.
AB  - Aqueous extracts of Centella asiatica L. Urban were encapsulated by an edible
      biopolymer, gelatin, which has no effect on their cosmetic activities. The
      nanoparticles were w/o-type spherical liposomes that had an average diameter of
      115.0nm. The encapsulation efficiency was estimated to be approximately 67%,
      which was relatively high for these aqueous extracts. The nanoparticles showed
      lower cytotoxicity (10%) in human skin fibroblast cells than the unencapsulated
      crude extract (15%) at 1.0mg/ml, this was possibly because a smaller amount of
      the extract was present in the nanoparticles. The nanoparticles efficiently
      reduced the expression of matrix metalloproteinase (MMP)-1 in UV-irradiated cells
      from 136.1% to 77.6% (UV-irradiated control) and inhibited hyaluronidase
      expression (>60%) at a concentration of 0.5mg/ml, which was higher than the
      levels produced by the unencapsulated crude extracts. The nanoparticles had a
      very high flux through mouse skin and also remained at relatively large
      concentrations in the derma when compared to the unencapsulated crude extracts.
      These results clearly indicate that the skin-protective activities of C. asiatica
      were significantly improved through the nano-encapsulation process. These
      findings also imply that a crude extract can be used and have the same efficacy
      as purified compounds, which should reduce the purification process and
      production costs.

PMID- 21893114
TI  - VP8* antigen produced in tobacco transplastomic plants confers protection against
      bovine rotavirus infection in a suckling mouse model.
AB  - Group A rotavirus is a major leading cause of diarrhea in mammalian species
      worldwide. In Argentina, bovine rotavirus (BRV) is the main cause of neonatal
      diarrhea in calves. VP4, one of the outermost capsid proteins, is involved in
      various virus functions. Rotavirus infectivity requires proteolytic cleavage of
      VP4, giving an N-terminal non-glycosilated sialic acid-recognizing domain (VP8*),
      and a C-terminal fragment (VP5*) that remains associated with the virion. VP8*
      subunit is the major determinant of the viral infectivity and one of the
      neutralizing antigens. In this work, the C486 BRV VP8* protein was produced in
      tobacco chloroplasts. Transplastomic plants were obtained and characterized by
      Southern blot, northern blot and western blot. VP8* was highly stable in the
      transplastomic leaves, and formed insoluble aggregates that were partially
      solubilized by sonication. The recombinant protein yield was 600 MUg/g of fresh
      tissue (FT). Both the soluble and insoluble fractions of the VP8* plant extracts
      were able to induce a strong immune response in female mice as measured by ELISA
      and virus neutralization test. Most important, suckling mice born to immunized
      dams were protected against oral challenge with virulent rotavirus. Results
      presented here contribute to demonstrate the feasibility of using antigens
      expressed in transplastomic plants for the development of subunit vaccines.

PMID- 21893115
TI  - Genomic analysis of grapevine leafroll associated virus-5 and related viruses.
AB  - The grapevine leafroll-associated viruses (GLRaVs) (Closteroviridae) represent an
      emerging threat to world grape production. One group of GLRaVs within the genus
      Ampelovirus, the GLRaV-4-like viruses (GLRaV-4LVs), contains a fragmented
      collection of seven viruses only two of which (GLRaV-Pr and GLRaCV) are fully
      sequenced. Here in reporting the sequence of GLRaV-5, a member of GLRaV-4LVs, we
      identify genomic elements common to the GLRaV-4LV group. Exclusive properties
      include a highly conserved p5 gene product and phylogenies for complete genes
      that, except for the p23 gene, are reliably monophyletic. In comparison with
      other members of the genus Ampelovirus, GLRaV-4LVs form a tight cluster for all
      genes analyzed. In addition, they all possess a conserved AlkB domain which is
      most similar to the more distantly related GLRaV-3, suggesting recombination. In
      silico RNA structural analyses revealed a conserved five stem-loop structure at
      the 3' untranslated region that extends to all GLRaV-4LVs, and the ampeloviruses
      Pineapple mealybug wilt-associated virus 1 and Pineapple mealybug wilt-associated
      virus 3. A conserved G-U rich stem loop was also found upstream of the ORF1a stop
      and 1b start codons. Taken together, this work allows for a more thorough
      contextualization of GLRaV-5 and the GLRaV-4LVs as a group within the genus
      Ampelovirus.

PMID- 21893116
TI  - V2 protein encoded by Tomato yellow leaf curl China virus is an RNA silencing
      suppressor.
AB  - The V2 protein of Tomato yellow leaf curl China virus (TYLCCNV) was identified as
      an RNA silencing suppressor by Agrobacterium-mediated co-infiltration. The V2
      protein could inhibit local RNA silencing, systemic RNA silencing of the green
      fluorescent protein (GFP) gene and the spread of a systemic GFP RNA silencing
      signal. However, the V2 could not interfere with the cell-to-cell spread of RNA
      silencing. Subcellular localization assay indicated that the V2 protein was
      distributed in the cytoplasm of Nicotiana benthamiana cells, and accumulated in
      irregular cytoplasmic bodies. The V2 bound 21nt and 24nt small interfering RNA
      (siRNA) duplexes and 24nt single-stranded (ss)-siRNA but not 21nt ss-siRNA in
      electrophoresis mobility shift assays. Expression of the V2 protein via the
      Potato virus X (PVX) vectors heterogenous system induced severe symptoms in N.
      benthamiana. In a yeast two-hybrid system, TYLCCNV V2 could interact with itself,
      but not with SlSGS3, which is known to been involved in RNA silencing pathway and
      to interact with a closely related Tomato yellow leaf curl virus (TYLCV) V2.
      These results indicate that TYLCCNV V2 is an RNA silencing suppressor, possibly
      through sequestering siRNA molecules.

PMID- 21893117
TI  - Molecular epidemiology of the SH (small hydrophobic) gene of human respiratory
      syncytial virus (HRSV), over 2 consecutive years.
AB  - Human respiratory syncytial virus (HRSV) strains were isolated from
      nasopharyngeal aspirates collected from 965 children between 2004 and 2005,
      yielding 424 positive samples. We sequenced the small hydrophobic protein (SH)
      gene of 117 strains and compared them with other viruses identified worldwide.
      Phylogenetic analysis showed a low genetic variability among the isolates but
      allowed us to classify the viruses into different genotypes for both groups,
      HRSVA and HRSVB. It is also shown that the novel BA-like genotype was well
      segregated from the others, indicating that the mutations are not limited to the
      G gene.

PMID- 21893118
TI  - Variants in the netrin-1 receptor UNC5C prevent apoptosis and increase risk of
      familial colorectal cancer.
AB  - BACKGROUND & AIMS: Expression of the netrin-1 dependence receptor UNC5C is
      reduced in many colorectal tumors; mice with the UNC5C mutations have increased
      progression of intestinal tumors. We investigated whether specific variants in
      UNC5C increase risk of colorectal cancer (CRC). METHODS: We analyzed the sequence
      of UNC5C in blood samples from 1801 patients with CRC and 4152 controls from 3
      cohorts (France, United States, and Finland). Almost all cases from France and
      the United States had familial CRC; of the Finnish cases, 92 of 984 were
      familial. We analyzed whether CRC segregates with the UNC5C variant A628K in 3
      families with histories of CRC. We also performed haplotype analysis to determine
      the origin of this variant. RESULTS: Of 817 patients with familial CRC, 14 had 1
      of 4 different, unreported missense variants in UNC5C. The variants p.Asp353Asn
      (encodes D353N), p.Arg603Cys (encodes R603C), and p.Gln630Glu (encodes Q630E) did
      not occur significantly more often in cases than controls. The variant
      p.Ala628Lys (A628K) was detected in 3 families in the French cohort (odds ratio,
      8.8; Wald's 95% confidence interval, 1.47-52.93; P = .03) and in 2 families in
      the US cohort (odds ratio, 1.9; P = .6) but was not detected in the Finnish
      cohort; UNC5C A628K segregated with CRC in families. Three families with A628K
      had a 109-kilobase identical haplotype that spanned most of UNC5C, indicating
      recent origin of this variant in white subjects (14 generations; 95% confidence
      interval, 6-36 generations). Transfection of HEK293T cells with UNC5C-A628K
      significantly reduced apoptosis compared with wild-type UNC5C, measured in an
      assay of active caspase-3. CONCLUSIONS: Inherited mutations in UNC5C prevent
      apoptosis and increase risk of CRC.

PMID- 21893119
TI  - Interleukin-13 damages intestinal mucosa via TWEAK and Fn14 in mice-a pathway
      associated with ulcerative colitis.
AB  - BACKGROUND & AIMS: TWEAK, a member of the tumor necrosis factor (TNF)
      superfamily, promotes intestinal epithelial cell injury and signals through the
      receptor Fn14 following irradiation-induced tissue damage and during development
      of colitis in mice. Interleukin (IL)-13, an effector of tissue damage in similar
      models, has been associated with the pathogenesis of ulcerative colitis (UC). We
      investigated interactions between TWEAK and IL-13 following mucosal damage in
      mice. METHODS: We compared patterns of gene expression in intestinal tissues from
      wild-type and TWEAK knockout mice following gamma-irradiation. Intestinal
      explants from these mice were used to detect cell damage induced by IL-13 and TNF
      alpha. Levels of messenger RNA for IL-13, TWEAK, and Fn14 were measured in
      mucosal samples from patients with UC. RESULTS: Based on gene expression
      analysis, TWEAK mediates gamma-irradiation-induced epithelial cell cycle arrest
      and apoptosis. However, TWEAK alone did not induce damage or apoptosis of primary
      intestinal epithelial cells. On the other hand, exogenous IL-13 activated caspase
      3 in naive intestinal explants; this process required TWEAK, Fn14, and secretion
      of endogenous TNF-alpha which was mediated by ADAM17. Conversely, activation of
      caspase by exogenous TNF-alpha required IL-13, TWEAK, and Fn14. In mucosa from
      patients with UC, messenger RNA levels of IL-13, TWEAK, and Fn14 increased with
      level of disease severity. CONCLUSIONS: IL-13-induced damage of intestinal
      epithelial cells requires TWEAK, its receptor (Fn14), and TNF-alpha. IL-13, TNF
      alpha, TWEAK, and Fn14 could perpetuate and aggravate intestinal inflammation in
      patients with UC.

PMID- 21893121
TI  - Non-viral gene therapy for neurological diseases, with an emphasis on targeted
      gene delivery.
AB  - Non-viral gene therapy systems are considered safer than viral delivery. This
      article reviews recent research describing novel, non-viral gene delivery to the
      central nervous system, with a special emphasis on receptor mediated gene
      delivery using antibodies (termed immunogenes) to specific receptors. By using
      targeting agents such as antibodies that can be retrogradely transported within
      neurons, non-viral gene therapies can deliver genes to specific neurons protected
      by the blood brain barrier. Components of effective non-viral gene therapy are
      described including DNA/RNA carriers, receptor-mediated endocytosis, endosomal
      escape and nuclear entry. In addition, stealth agents such as polyethylene glycol
      that can be used to improve in-vivo delivery are discussed. The value of
      immunogenes as therapeutic agents for fatal diseases such as Amyotrophic Lateral
      Sclerosis is significant but further in-vivo work to confirm efficacy is required
      before truly effective therapies can be achieved.

PMID- 21893120
TI  - Trypsin reduces pancreatic ductal bicarbonate secretion by inhibiting CFTR Cl-
      channels and luminal anion exchangers.
AB  - BACKGROUND & AIMS: The effects of trypsin on pancreatic ductal epithelial cells
      (PDECs) vary among species and depend on the localization of proteinase-activated
      receptor 2 (PAR-2). We compared PAR-2 localization in human and guinea-pig PDECs,
      and used isolated guinea pig ducts to study the effects of trypsin and a PAR-2
      agonist on bicarbonate secretion. METHODS: PAR-2 localization was analyzed by
      immunohistochemistry in guinea pig and human pancreatic tissue samples (from 15
      patients with chronic pancreatitis and 15 without pancreatic disease).
      Functionally, guinea pig PDECs were studied by microperfusion of isolated ducts,
      measurements of intracellular pH and intracellular Ca(2+) concentration, and
      patch clamp analysis. The effect of pH on trypsinogen autoactivation was assessed
      using recombinant human cationic trypsinogen. RESULTS: PAR-2 localized to the
      apical membrane of human and guinea pig PDECs. Trypsin increased intracellular
      Ca(2+) concentration and intracellular pH and inhibited secretion of bicarbonate
      by the luminal anion exchanger and the cystic fibrosis transmembrane conductance
      regulator (CFTR) Cl(-) channel. Autoactivation of human cationic trypsinogen
      accelerated when the pH was reduced from 8.5 to 6.0. PAR-2 expression was
      strongly down-regulated, at transcriptional and protein levels, in the ducts of
      patients with chronic pancreatitis, consistent with increased activity of
      intraductal trypsin. Importantly, in PAR-2 knockout mice, the effects of trypsin
      were markedly reduced. CONCLUSIONS: Trypsin reduces pancreatic ductal bicarbonate
      secretion via PAR-2-dependent inhibition of the apical anion exchanger and the
      CFTR Cl(-) channel. This could contribute to the development of chronic
      pancreatitis by decreasing luminal pH and promoting premature activation of
      trypsinogen in the pancreatic ducts.

PMID- 21893122
TI  - Genetically-manipulated adult stem cells as therapeutic agents and gene delivery
      vehicle for wound repair and regeneration.
AB  - Wound therapy remains a clinical challenge and much effort has been focused on
      the development of novel therapeutic approaches for wound management. New
      knowledge about the way in which signals control wound cellular and molecular
      behavior has promoted the topical application of multipotent stem cells and
      bioactive molecules to injured tissue, for skin regeneration with less scar
      formation. However, limited clinical success indicates that the effective
      delivery of polypeptides and therapeutic cells, with controlled releasing
      profile, is a major challenge which is yet to be overcome. Recently, a technique
      in which the genetically-manipulated stem cells were used both as the therapeutic
      agents and the vehicle for gene delivery for wound treatment - a method which
      serves to provide regenerative cells and bioactive genes within an optimal
      environment of regulatory molecular expression for wound sites - has emerged as a
      promising strategy for wound regenerative therapy. In this article, the roles of
      adult stem cells - as the therapeutics and the vehicles in these advanced
      biomimetic drug delivery systems for wound regeneration medicine - are
      scrutinized to indicate their mechanisms, characteristics, broad applicability
      and future lines of investigation.

PMID- 21893123
TI  - Laryngeal mask airway for babies: uncharted waters.

PMID- 21893125
TI  - Comparison of intraosseous versus central venous vascular access in adults under
      resuscitation in the emergency department with inaccessible peripheral veins.
AB  - INTRODUCTION: Current European Resuscitation Council (ERC) guidelines recommend
      intraosseous (IO) vascular access, if intravenous (IV) access is not readily
      available. Because central venous catheterisation (CVC) is an established
      alternative for in-hospital resuscitation, we compared IO access versus landmark
      based CVC in adults with difficult peripheral veins. METHODS: In this prospective
      observational study we investigated success rates on first attempt and procedure
      times of IO access versus central venous catheterisation (CVC) in adults (>= 18
      years of age) with inaccessible peripheral veins under trauma or medical
      resuscitation in a level I trauma centre emergency department. RESULTS: Forty
      consecutive adults under resuscitation were analysed, each receiving IO access
      and CVC simultaneously. Success rates on first attempt were significantly higher
      for IO cannulation than CVC (85% versus 60%, p=0.024) and procedure times were
      significantly lower for IO access compared to CVC (2.0 versus 8.0 min, p<0.001).
      As for complications, failure of IO access was observed in 6 patients, while 2 or
      more attempts of CVC were necessary in 16 patients. No other relevant
      complications like infection, bleeding or pneumothorax were observed.
      CONCLUSIONS: IO vascular access is a reliable bridging method to gain vascular
      access for in-hospital adult patients under resuscitation with difficult
      peripheral veins. Moreover, IO access is more efficacious with a higher success
      rate on first attempt and a lower procedure time compared to landmark-based CVC.

PMID- 21893126
TI  - Hepatocellular carcinoma with intracardiac extension.

PMID- 21893127
TI  - Prevalence and mechanisms of malnutrition in patients with advanced liver
      disease, and nutrition management strategies.
AB  - Malnutrition is prevalent among cirrhotic patients and is an important prognostic
      factor. Etiologic factors include hypermetabolism, malabsorption, altered
      nutrient metabolism, and anorexia. It is a challenge to manage nutrition in
      cirrhotic patients because of alterations to metabolic and storage functions of
      the liver; use of traditional assessment tools, such as anthropometric and
      biometric measures, is difficult because of complications such as ascites and
      inflammation. In addition to meeting macro- and micronutrient requirements, the
      composition and timing of supplements have been proposed to affect efficacy of
      nutrition support. Studies have indicated that branched chain aromatic acid can
      be given as therapeutic nutrients, and that probiotics and nocturnal feeding
      improve patient outcomes.

PMID- 21893128
TI  - An assessment of the severity of interstitial pancreatitis.
AB  - BACKGROUND & AIMS: There is limited information on the incidence of and factors
      associated with severe disease among patients with interstitial pancreatitis
      (IP). We evaluated a large cohort of patients with IP and compared data with
      those from patients with extrapancreatic necrosis (EXPN). METHODS: We evaluated
      149 consecutive patients with IP admitted over a 2.5-year period. Transferred
      patients were excluded. We collected data on age, Charlson comorbidity score
      (CCI), measures of severity on admission or within 24 hours (Acute Physiology and
      Chronic Health Evaluation II, bedside index for severity of acute pancreatitis
      scores), persistent (>48 h) systemic inflammatory response syndrome, persistent
      organ failure, need for intensive care unit, length of hospital stay (in days),
      and mortality. We also analyzed levels of severity among those with IP and EXPN.
      Statistical analysis was performed using SAS version 9.1 (Cary, NC). RESULTS:
      Among the patients with IP, the median CCI score was 1, the median Acute
      Physiology and Chronic Health Evaluation II score was 7, and the median bedside
      index for severity of acute pancreatitis score was 1. In addition, the median
      length of hospital stay was only 4 days; only 1% had persistent organ failure and
      only 1% to 2% required intervention. The mortality rate of IP was 3%; it was
      associated significantly with comorbidity (the median CCI scores of nonsurvivors
      and survivors was 4 and 1, respectively, P = .003). Patients with EXPN had
      greater levels of disease severity, compared with patients with IP. CONCLUSIONS:
      IP is severe in only 1% to 3% of patients; mortality of IP is associated strongly
      with comorbidity. EXPN is more frequently severe than IP; EXPN must be
      distinguished from IP in clinical studies.

PMID- 21893129
TI  - Muscle wasting is associated with mortality in patients with cirrhosis.
AB  - BACKGROUND & AIMS: Sarcopenia, defined as a low level of muscle mass, occurs in
      patients with cirrhosis. We assessed its incidence among cirrhotic patients
      undergoing evaluation for liver transplantation to investigate associations
      between sarcopenia and mortality and prognosis. METHODS: We studied 112 patients
      with cirrhosis (78 men; mean age, 54 +/- 1 years) who were consecutively
      evaluated for liver transplantation and had a computed tomography scan at the
      level of the third lumbar (L3) vertebrae to determine the L3 skeletal muscle
      index; sarcopenia was defined by using previously published, sex-specific
      cutoffs. RESULTS: Of the patients studied, 45 (40%) had sarcopenia. Univariate
      Cox analysis associated mortality with ascites (hazard ratio [HR], 2.12; P =
      .04), encephalopathy (HR, 1.99; P = .04), level of bilirubin (HR, 1.007; P <
      .01), international normalized ratio (HR, 7.69; P < .001), level of creatinine
      (HR, 1.01; P = .005), level of albumin (HR, 94; P = .008), serum level of sodium
      (HR, 89; P < .001), Model for End-Stage Liver Disease (MELD) score (HR, 1.14; P <
      .01), Child-Pugh score (HR, 2.84; P < .001), and sarcopenia (HR, 2.18; P = .006).
      By multivariate Cox analysis, only Child-Pugh (HR, 1.85; P = .04) and MELD scores
      (HR, 1.08; P = .001) and sarcopenia (HR, 2.21; P = .008) were independently
      associated with mortality. The median survival time for patients with sarcopenia
      was 19 +/- 6 months, compared with 34 +/- 11 months among nonsarcopenia patients
      (P = .005). There was a low level of correlation between L3 skeletal muscle index
      and MELD (r = -0.07; P = .5) and Child-Pugh scores (r = -0.14; P = .1).
      CONCLUSIONS: Sarcopenia is associated with mortality in patients with cirrhosis.
      It does not correlate with the degree of liver dysfunction evaluated by using
      conventional scoring systems. Scoring systems should include evaluation of
      sarcopenia to better assess mortality among patients with cirrhosis.

PMID- 21893130
TI  - Variceal hemorrhage of ascending colon.

PMID- 21893131
TI  - Decreasing levels of HBsAg predict HBsAg seroclearance in patients with inactive
      chronic hepatitis B virus infection.
AB  - BACKGROUND & AIMS: Serum levels of hepatitis B surface antigen (HBsAg) decrease
      gradually during chronic hepatitis B virus infection. We investigated the
      association between levels of HBsAg and HBsAg seroclearance. METHODS: We studied
      data from 46 patients who underwent spontaneous seroclearance of HBsAg (median
      age at seroclearance, 48 y; 87% male; 76% infected with genotype B). There were
      46 controls matched for age, sex, and hepatitis B virus genotype, and e antigen
      status with persistently normal levels of alanine aminotransferase and
      seropositive for HBsAg. Levels of HBsAg were assessed in serum specimens
      collected 5 years 3 years, and 1 year before HBsAg seroclearance (or before the
      last examination, for controls). RESULTS: The decrease in HBsAg level was
      significant and accelerated within the 3 years before HBsAg seroclearance; there
      was no significant decrease in serum level of HBsAg among controls (P < .0001).
      The positive predictive value (PPV) for HBsAg seroclearance within 1 year was 36%
      among patients with HBsAg levels of 200 IU/mL, increasing to 44%, 54%, and 67%
      among patients with HBsAg levels of 100 IU/mL, 50 IU/mL, or 10 IU/mL,
      respectively; the negative predictive value (NPV) for these levels was 96% or
      greater. The combination of HBsAg level less than 200 IU/mL and a decrease of 1
      or more log(10) IU/mL in a preceding 2-year period had PPVs of 97% and 100% for
      HBsAg seroclearance at 1 and 3 years, respectively; the NPVs were 100% and 92%,
      respectively. CONCLUSIONS: The decrease in the level of HBsAg accelerates during
      the 3 years before HBsAg seroclearance. Levels of HBsAg of 200 IU/mL or less have
      high NPVs for HBsAg seroclearance; PPVs increase to 97% to 100% when combined
      with a 1 log IU/mL or more decrease in level of HBsAg over a 2-year period.

PMID- 21893132
TI  - The vermiform appendix and recurrent Clostridium difficile infection: a curious
      connection.

PMID- 21893133
TI  - A pancreatic mass and bilateral pitting pedal edema: nothing is ever what it
      seems.

PMID- 21893134
TI  - Inflammatory bowel disease is associated with poor outcomes of patients with
      primary sclerosing cholangitis.
AB  - BACKGROUND & AIMS: Little is known about the exact etiology of primary sclerosing
      cholangitis (PSC); epidemiologic data are scarce. We performed a population-based
      epidemiologic study of PSC in Canterbury, New Zealand. METHODS: By using multiple
      case-finding methods, we searched public and private adult and pediatric
      outpatient clinics, hospital discharge summaries, and radiology and pathology
      reports to identify all cases of PSC in the region. Cases were included if PSC
      was identified by endoscopic retrograde cholangiography, magnetic resonance
      cholangiography, or liver biopsy analysis (n = 79). RESULTS: The incidence of PSC
      in 2008 was 1.6 per 100,000 persons (95% confidence interval [CI], 0.5-2.7). The
      point prevalence on December 31, 2008, was 11.7 per 100,000 persons (95% CI, 8.7
      14.8). The mean and median ages at diagnosis were 50 years (95% CI, 46-53 years)
      and 49 years (range, 17-80 years), respectively. Patients who had inflammatory
      bowel disease (IBD) presented with PSC earlier than those without IBD (P = .003),
      were more likely to develop serious malignant complications (P = .017), and were
      more likely to require liver transplantation or die (P = .03). CONCLUSIONS: In a
      population-based epidemiology study of PSC in Canterbury, New Zealand, we
      observed large differences between PSC patients with or without concurrent IBD in
      age at diagnosis, development of cancer, mortality, and requirement for liver
      transplantation. IBD therefore affects outcomes of patients with PSC, an
      important observation that requires further study.

PMID- 21893135
TI  - Magnetically enhanced nucleic acid delivery. Ten years of magnetofection-progress
      and prospects.
AB  - Nucleic acids carry the building plans of living systems. As such, they can be
      exploited to make cells produce a desired protein, or to shut down the expression
      of endogenous genes or even to repair defective genes. Hence, nucleic acids are
      unique substances for research and therapy. To exploit their potential, they need
      to be delivered into cells which can be a challenging task in many respects.
      During the last decade, nanomagnetic methods for delivering and targeting nucleic
      acids have been developed, methods which are often referred to as magnetofection.
      In this review we summarize the progress and achievements in this field of
      research. We discuss magnetic formulations of vectors for nucleic acid delivery
      and their characterization, mechanisms of magnetofection, and the application of
      magnetofection in viral and nonviral nucleic acid delivery in cell culture and in
      animal models. We summarize results that have been obtained with using
      magnetofection in basic research and in preclinical animal models. Finally, we
      describe some of our recent work and end with some conclusions and perspectives.

PMID- 21893136
TI  - Identifying risk of cardiac events in short QT syndrome.

PMID- 21893137
TI  - Development and validation of a risk score to predict early mortality in
      recipients of implantable cardioverter-defibrillators.
AB  - BACKGROUND: Current guidelines do not recommend implantable cardioverter
      defibrillator (ICD) implantation in patients with a life expectancy of <1 year.
      Better methods are needed for identifying patients at high risk for early
      mortality despite ICD therapy. OBJECTIVE: To develop and validate a risk
      prediction score to identify patients at high risk for death within 1 year
      despite ICD therapy. DESIGN: Detailed clinical data were collected on a large
      observational cohort of ICD patients from 3 tertiary care centers. One-third of
      the patients were randomly selected to form the prediction group (PG) from which
      a risk score was developed using logistic regression. This score was then applied
      to the remaining two-thirds of the cohort (validation group [VG]) to assess the
      risk score's predictive accuracy. RESULTS: The total cohort included 2717 ICD
      patients (mean age = 64.6 +/- 14.5, male = 77.2%, primary prevention = 74.7%). A
      simple risk score incorporating peripheral arterial disease, age >= 70 years,
      creatinine >= 2.0 mg/dL, and ejection fraction <=20% (PACE) accurately predicted
      1-year mortality in the VG. Patients with a risk score of >=3 had a >4-fold
      excess 1-year mortality compared with patients with a risk score of <3 (16.5% vs
      3.5%; P <.0001). LIMITATION: Risk reduction provided by ICD therapy in this
      cohort is not known given the lack of a control group. CONCLUSIONS: A simple risk
      score accurately predicts 1-year mortality in ICD patients, as patients with a
      PACE risk score of >=3 are at high risk despite ICD therapy.

PMID- 21893138
TI  - Cardiac biexcitability: two ways to catch a wave.

PMID- 21893139
TI  - The receptor guanylate cyclase Gyc76C and a peptide ligand, NPLP1-VQQ, modulate
      the innate immune IMD pathway in response to salt stress.
AB  - Receptorguanylate cyclases (rGCs) modulate diverse physiological processes
      including mammalian cardiovascular function and insect eclosion. The Drosophila
      genome encodes several receptor and receptor-like GCs, but no ligand for any
      Drosophila rGC has yet been identified. By screening peptide libraries in
      Drosophila S2 cells, the Drosophila peptide NPLP1-VQQ (NLGALKSSPVHGVQQ) was shown
      to be a ligand for the rGC, Gyc76C (CG42636, previously CG8742, l(3)76BDl, DrGC
      1). In the adult fly, expression of Gyc76C is highest in immune and stress
      sensing epithelial tissues, including Malpighian tubules and midgut; and NPLP1
      VQQ stimulates fluid transport and increases cGMP content in tubules. cGMP
      signaling is known to modulate the activity of the IMD innate immune pathway in
      tubules via activation and nuclear translocation of the NF-kB orthologue, Relish,
      resulting in increased anti-microbial peptide (AMP) gene expression; and so NPLP1
      VQQ might act in immune/stress responses. Indeed, NPLP1-VQQ induces nuclear
      translocation of Relish in intact tubules and increases expression of the anti
      microbial peptide gene, diptericin. Targeted Gyc76C RNAi to tubule principal
      cells inhibited both NPLP1-VQQ-induced Relish translocation and diptericin
      expression. Relish translocation and increased AMP gene expression also occurs in
      tubules in response to dietary salt stress. Gyc76C also modulates organismal
      survival to salt stress - ablation of Gyc76C expression in only tubule principal
      cells prevents Relish translocation, reduces diptericin expression, and reduces
      organismal survival in response to salt stress. Thus, the principal-cell
      localized NPLP1-VQQ/Gyc76C cGMP pathway acts to signal environmental (salt)
      stress to the whole organism.

PMID- 21893140
TI  - Ghrelin acylation and metabolic control.
AB  - Since its discovery, many physiologic functions have been ascribed to ghrelin, a
      gut derived hormone. The presence of a median fatty acid side chain on the
      ghrelin peptide is required for the binding and activation of the classical
      ghrelin receptor, the growth hormone secretagogue receptor (GHSR)-1a. Ghrelin O
      acyl transferase (GOAT) was recently discovered as the enzyme responsible for
      this acylation process. GOAT is expressed in all tissues that have been found to
      express ghrelin and has demonstrated actions on several complex endocrine organ
      systems such as the hypothalamus-pituitary-gonadal, insular and adrenal axis as
      well as the gastrointestinal (GI) tract, bone and gustatory system. Ghrelin
      acylation is dependent on the function of GOAT and the availability of substrates
      such as proghrelin and short- to medium-chain fatty acids (MCFAs). This process
      is governed by GOAT activity and has been shown to be modified by dietary lipids.
      In this review, we provided evidence that support an important role of GOAT in
      the regulation of energy homeostasis and glucose metabolism by modulating acyl
      ghrelin (AG) production. The relevance of GOAT and AG during periods of
      starvation remains to be defined. In addition, we summarized the recent
      literature on the metabolic effects of GOAT specific inhibitors and shared our
      view on the potential of targeting GOAT for the treatment of metabolic disorders
      such as obesity and type 2 diabetes.

PMID- 21893141
TI  - Polyelectrolyte coating of iron oxide nanoparticles for MRI-based cell tracking.
AB  - Iron oxide-based magnetic nanoparticles (MNPs) offer unique properties for cell
      tracking by magnetic resonance imaging (MRI) in cellular immunotherapy. In this
      study, we investigated the uptake of chemically engineered NPs into antigen
      presenting dendritic cells (DCs). DCs are expected to perceive MNPs as foreign
      antigens, thus exhibiting the capability to immunologically sense MNP surface
      chemistry. To systematically evaluate cellular uptake and T2/T2(*) MR imaging
      properties of MNPs, we synthesized polymer-based MNPs by employing layer-by-layer
      (LbL) technology. Thereby, we achieved modification of particle shell parameters,
      such as size, surface charge, and chemistry. We found that subcellular packaging
      of MNPs rather than MNP content in DCs influences MR imaging quality. Increased
      local intracellular electron density as inferred from transmission electron
      microscopy (TEM) strongly correlated with enhanced contrast in MRI. Thus, LbL
      tailoring of MNP shells using polyelectrolytes that impact on uptake and
      subcellular localization can be used for modulating MR imaging properties. FROM
      THE CLINICAL EDITOR: In this study, layer-by-layer tailoring of magnetic NP
      shells was performed using polyelectrolytes to improve uptake by dendritic cells
      for cell-specific MR imaging. The authors conclude that polyelectrolyte modified
      NP-s can be used for modulating improving MR imaging quality by increasing
      subcellular localization.

PMID- 21893143
TI  - Do the initial serum level changes of sCD26 have ability to predict successful
      treatment with IFN-alpha among naive chronic hepatitis B patients?
AB  - INTRODUCTION: Hepatitis B is a major health problem with serious consequences. In
      hepatitis B treatment host cellular immune responses have a determinant role and
      T helper cells are the main active members of immune system against virological
      infection. The aims of this study are to investigate response rate of patients to
      INF-alpha therapy and evaluation of sCD26 and sCD30 roles as presenters of T
      cells activities in predicting the outcome of therapy in chronic hepatitis B
      patients. METHODS AND MATERIALS: Fifty three chronic hepatitis B patients
      received IFN-alpha 9 MU S.C three times weekly for 24 weeks, and were followed up
      for 24 weeks. Serum levels of sCD26 and sCD30, before, 1 and 3 months after
      treatment commencement were evaluated in 53 chronic hepatitis B patients and 30
      healthy individuals as control group. RESULTS: Normal level of ALT was seen in
      64.1% (34/53) of patients and undetectable DNA was observed in 39.6% (21 out of
      53) of them. Finally, 33.9% (18/53) of patients obtained sustain virological
      response. CD26 levels changes was correlated with response to treatment and
      significantly (p<0.001) increased during first 3 months of treatment among
      patients with successful response to therapy. CONCLUSION: Interferon is an
      effective and safe treatment for chronic hepatitis B patients and sCD26 serum
      level changes might be useful in predicting the outcome of therapy in naive
      chronic hepatitis B patients undergoing treatment with IFN-alpha, as it can help
      clinicians for withdrawing non-responder patients for prevention of adverse
      events and economical burden.

PMID- 21893142
TI  - Adjuvant effect of bacterial outer membrane vesicles with penta-acylated
      lipopolysaccharide on antigen-specific T cell priming.
AB  - Outer membrane vesicles (OMV) are nano-sized spherical blebs shed by Gram
      negative bacteria and have been utilized in vaccine development. In the present
      study, we evaluated T cell adjuvant activity of OMV with strictly penta-acylated
      LPS produced by DeltamsbB/DeltapagP mutant of non-pathogenic Escherichia coli
      W3110 (mOMV) compared to OMV with hexa-acylated LPS produced by wild-type E. coli
      W3110 (wOMV). Penta-acylation of LPS renders mOMV less endotoxic than wOMV in in
      vitro and in vivo toxicity assays. In mice, mOMV has adjuvant activity on T cell
      priming not only in KLH protein immunization but also in SIINFEKL peptide
      immunization. The T-cell adjuvant activity of mOMV was comparable to that of wOMV
      and LPS and was abrogated in TLR4 K/O mice. In innate immunity, mOMV stimulated
      BMDCs to up-regulate co-stimulatory and antigen-presenting molecules and to
      produce pro-inflammatory cytokines in a TLR4-dependent manner. Of note, mOMV
      induced cytokine production at a significantly less extent compared with wOMV.
      Taken together, we propose that mOMV with penta-acylated LPS is a safe vaccine
      adjuvant for T cell priming and can be used in vaccine development against viral
      diseases and cancer.

PMID- 21893144
TI  - The sensitivity of BCG scar as an indicator of previous vaccination among
      Sudanese infants.
AB  - BACKGROUND: Tuberculosis remains a major cause of morbidity and mortality
      worldwide. Bacille Calmette Guerin (BCG) is the current vaccine for tuberculosis.
      The absence or presence of a scar is used as an indicator of previous
      vaccination. OBJECTIVES: To determine the sensitivity of the BCG scar as an
      indicator of previous vaccination. METHODS: We conducted a descriptive hospital
      based study of 100 infants attending two centres for routine vaccination and
      weight checks. Data analysis was done using statistical package for social
      sciences. RESULTS: We surveyed 100 infants, the BCG scar was present in 83%, the
      average size of the BCG scar was found to be 3mm. CONCLUSION: The BCG scar is a
      sensitive indicator of previous vaccination after the administration of the
      vaccine in the first month of life.

PMID- 21893145
TI  - MMR vaccine effectiveness in an outbreak that involved day-care and primary
      schools.
AB  - OBJECTIVE: In 2006, a large measles outbreak occurred in Catalonia (Spain), where
      the immunization schedule included two doses of MMR vaccine at 15 months and 4
      years. The aim of this study was to investigate the vaccine effectiveness (VE) of
      MMR in children attending day-care and pre-school centres and to estimate the
      number of cases that would have been avoided by administering the first dose of
      MMR at 12 months. METHODS: A retrospective cohort study was carried out between
      October 2006 and January 2007 in day-care and pre-school centres with confirmed
      measles cases. VE was calculated in children aged >=15 months without previous
      measles infection. Cases avoided by advancing the first dose of MMR to 12 months
      were estimated by calculating the basic and effective reproduction number in
      centres where transmission outside the class was observed. RESULTS: Fifteen
      centres and 1394 children were included. There were 77 confirmed cases (attack
      rate=5.5%). Vaccination coverage of the 1121 children aged >=15 months was 91.6%
      and VE was 96% (95%CI 89-98%). There were 33 (41%) cases in the 81 children aged
      12-14 months. Advancing the first dose to 12 months would have prevented 74 cases
      (91.5%) and lowered the attack rate from 41% to 8.6%. CONCLUSIONS: Over 90% of
      cases in children aged 12-14 months would have been avoided by MMR administration
      at 12 rather than 15 months. We strongly recommend advancing the first dose of
      MMR to 12 months in order to reduce the risk of measles outbreaks.

PMID- 21893146
TI  - Diminished immunogenicity to pandemic H1N1 2009 influenza vaccine in subjects
      with severe motor and intellectual disability.
AB  - Subjects with severe motor and intellectual disability (SMID) are considered to
      be debilitated and at high risk of influenza infection. However, the safety and
      immunogenicity of pandemic H1N1 (pH1N1) vaccine in these subjects have not been
      reported. We measured the hemagglutination inhibition antibody titer and
      calculated the geometric mean titer ratio (GMTR), seroprotection rate, and
      seroconversion rate in 104 subjects with SMID (mean age+/-standard deviation
      40.1+/-12.9 years), and in 179 healthcare workers (40.7+/-10.4 years) in a long
      term care facility. Antibody responses after the first dose of pH1N1 vaccine
      among workers were greater than the European Medicines Evaluation Agency criteria
      and US Food and Drug Administration (FDA) criteria: the seroprotection rate was
      79.9% (95% confidence interval (CI) 73.3-85.5), the seroconversion rate was 77.9%
      (95%CI: 70.8-84.0), and GMTR was 7.3 (95%CI: 6.9-7.8). Responses among subjects
      with SMID were lower than the FDA criteria: the seroprotection rate was 56.3%
      (95%CI: 46.2-66.1), the seroconversion rate was 54.1% (95%CI: 43.7-64.2), and
      GMTR was 5.4 (95%CI: 4.9-5.9). Any additional antibody response induced by the
      second dose of vaccine among subjects with SMID was limited. Multivariate
      analysis indicated that subjects with SMID had a significantly lower
      seroprotection rate (odds ratio (OR) 0.37, 95%CI: 0.20-0.66) and seroconversion
      rate (OR 0.34, 95%CI: 0.20-0.59) than healthcare workers. No serious adverse
      reaction was reported in either group. These results indicate that a single dose
      of pH1N1 vaccine does not induce sufficient immunity among subjects with SMID,
      and a second dose is likely to be ineffective because of diminished
      immunogenicity. Further study is required to determine if vaccination over
      consecutive influenza seasons can improve immunogenicity in subjects with SMID.

PMID- 21893147
TI  - Immunogenicity and safety of monovalent influenza A (H1N1) 2009 in HIV-infected
      Thai children.
AB  - To evaluate the immunogenicity and safety of the monovalent pandemic influenza A
      (H1N1) 2009 (pH1N1) vaccine in HIV-infected Thai children, 2 doses, 28days apart,
      of non-adjuvant monovalent pH1N1 vaccine (Panenza((r)) by Sanofi Pasteur,
      15MUg/dose) provided by the National Health Promotion Program of the Thai
      Ministry of Public Health were given to HIV-infected children. Immunogenicity was
      measured by hemagglutination inhibition test (HAI) using two antigens, pH1N1
      (A/Thailand/104/09) and seasonal influenza A H1N1 (A/Brisbane/59/07-like), at
      baseline, and 28days after each dose. Serologic response was defined as four-fold
      rising of HAI titer or HAI titer >=1:40 for those with baseline titer <=1:10.
      Adverse events were recorded for 7days after each vaccination. Of the 119 HIV
      infected children enrolled, 60 (50.4%) were female with a median (IQR) age of
      10.4 (7.2-13.7)years. All but 2 (98.3%) children were receiving antiretroviral
      therapy. At baseline, the median CD4 cell count was 782 (570-1149)cells/mm(3), 91
      (80.5%) children had HIV RNA level <40copies/ml. The baseline HAI titer >=1:40
      for pH1N1 and seasonal H1N1 were 45.4%, and 39.5%, respectively. At 28 days after
      doses 1 and 2, the serologic response rates for pH1N1 were 54.2% and 67.8% with
      the geometric mean titer of 109.9 and 141.8; and serologic response rate when
      tested with seasonal H1N1 were 2.5% and 3.5%, respectively. The presence of
      baseline HAI titer for pH1N1 or seasonal H1N1 was found to be associated with
      serologic response. The vaccine was well tolerated. The results suggested that
      monovalent pH1N1 vaccine was immunogenic and safe in well controlled HIV-infected
      children with low level of cross reacting antibody to seasonal H1N1.

PMID- 21893148
TI  - Causality assessment of serious neurologic adverse events following 2009 H1N1
      vaccination.
AB  - BACKGROUND: Adverse events occurring after vaccination are routinely reported to
      the Vaccine Adverse Event Reporting System (VAERS). We studied serious adverse
      events (SAEs) of a neurologic nature reported after receipt of influenza A (H1N1)
      2009 monovalent vaccine during the 2009-2010 influenza season. Investigators in
      the Clinical Immunization Safety Assessment (CISA) network sought to characterize
      these SAEs and to assess their possible causal relationship to vaccination.
      METHODS: Centers for Disease Control and Prevention (CDC) and Food and Drug
      Administration (FDA) physicians reviewed all SAE reports (as defined by the Code
      of Federal Regulations, 21CFRS314.80) after receipt of H1N1 vaccine reported to
      VAERS between October 1, 2009 and March 31, 2010. Non-fatal SAE reports with
      neurologic presentation were referred to CISA investigators, who requested and
      reviewed additional medical records and clinical information as available. CISA
      investigators assessed the causal relationship between vaccination and the event
      using modified WHO criteria as defined. RESULTS: 212 VAERS reports of non-fatal
      serious neurological events were referred for CISA review. Case reports were
      equally distributed by gender (50.9% female) with an age range of 6 months to 83
      years (median 38 years). The most frequent diagnoses reviewed were: Guillain
      Barre Syndrome (37.3%), seizures (10.8%), cranial neuropathy (5.7%), and acute
      disseminated encephalomyelitis (3.8%). Causality assessment resulted in
      classification of 72 events as "possibly" related (33%), 108 as "unlikely"
      related (51%), and 20 as "unrelated" (9%) to H1N1 vaccination; none were
      classified as "probable" or "definite" and 12 were unclassifiable (6%).
      CONCLUSION: The absence of a specific test to indicate whether a vaccine
      component contributes to the pathogenesis of an event occurring within a
      biologically plausible time period makes assessing causality difficult. The
      development of standardized protocols for providers to use in evaluation of
      adverse events following immunization, and rapid identification and follow-up of
      VAERS reports could improve causality assessment.

PMID- 21893149
TI  - Reasons related to non-vaccination and under-vaccination of children in low and
      middle income countries: findings from a systematic review of the published
      literature, 1999-2009.
AB  - OBJECTIVE: Despite increases in routine vaccination coverage during the past
      three decades, the percent of children completing the recommended vaccination
      schedule remains below expected targets in many low and middle income countries.
      In 2008, the World Health Organization Strategic Advisory Group of Experts on
      Immunization requested more information on the reasons that children were under
      vaccinated (receiving at least one but not all recommended vaccinations) or not
      vaccinated in order to develop effective strategies and interventions to reach
      these children. METHODS: A systematic review of the peer-reviewed literature
      published from 1999 to 2009 was conducted to aggregate information on reasons and
      factors related to the under-vaccination and non-vaccination of children. A
      standardized form was used to abstract information from relevant articles
      identified from eight different medical, behavioural and social science
      literature databases. FINDINGS: Among 202 relevant articles, we abstracted 838
      reasons associated with under-vaccination; 379 (45%) were related to immunization
      systems, 220 (26%) to family characteristics, 181 (22%) to parental attitudes and
      knowledge, and 58 (7%) to limitations in immunization-related communication and
      information. Of the 19 reasons abstracted from 11 identified articles describing
      the non-vaccinated child, 6 (32%) were related to immunization systems, 8 (42%)
      to parental attitudes and knowledge, 4 (21%) to family characteristics, and 1
      (5%) to communication and information. CONCLUSIONS: Multiple reasons for under
      vaccination and non-vaccination were identified, indicating that a multi-faceted
      approach is needed to reach under-vaccinated and unvaccinated children.
      Immunization system issues can be addressed through improving outreach services,
      vaccine supply, and health worker training; however, under-vaccination and non
      vaccination linked to parental attitudes and knowledge are more difficult to
      address and likely require local interventions.

PMID- 21893150
TI  - Attitudes and perceptions of private pediatricians regarding polio immunization
      in India.
AB  - BACKGROUND: India has faced considerable challenges in eradicating polio. Uttar
      Pradesh (UP) and Bihar are the two states in India where transmission of polio
      has never been interrupted. Private pediatricians are important stakeholders for
      vaccine delivery and maintaining public confidence in vaccines. The purpose of
      this study was to investigate the attitudes and perceptions of pediatricians in
      India regarding polio immunization and their opinions about various strategies
      regarding polio eradication in the country. METHODS: A random sample of 785
      pediatricians belonging to the Indian Academy of Pediatrics (IAP) were selected
      for the survey with over sampling of members located in Bihar and UP. Potential
      participants were either contacted by phone or sent a self-administered anonymous
      questionnaire by mail. For this analysis both sets of responses were combined.
      Surveys were conducted from June 2009 to June 2010. RESULTS: A total of 398
      surveys were completed (51%). Nearly all respondents indicated that polio
      eradication is still an important priority (99.7%). Ninety-six percent of
      pediatricians believed that strengthening routine immunization efforts remains
      the best way to eradicate polio in endemic areas. Other measures thought to be
      important in eradicating polio are mass campaigns with IPV (73%) and mass
      campaigns with bivalent OPV (59%). Pediatricians also identified several barriers
      to polio eradication which included parents' lack of awareness of the importance
      of polio vaccination (88.8%), parents' lack of confidence in polio vaccine
      (64.0%), religious beliefs (59.2%), fear of side effects (59.2%), lack of time or
      priority (56.6%), superstition (50.3%) and cultural beliefs (46.4%). CONCLUSION:
      There is still strong support for polio eradication efforts among IAP members.
      Pediatricians in India strongly believe that improving the coverage of routine
      immunization remains the best way to eradicate polio. There is an urgent need to
      improve awareness, build confidence in the program, and remove barriers among
      parents.

PMID- 21893151
TI  - Effect of 7-valent pneumococcal conjugate vaccine on nasopharyngeal carriage with
      Haemophilus influenzae and Moraxella catarrhalis in a randomized controlled
      trial.
AB  - Seven-valent CRM197-conjugated pneumococcal conjugate vaccine (PCV7(CRM197))
      reduces both vaccine serotype nasopharyngeal colonization and vaccine serotype
      acute otitis media by 50-60%. However, overall pneumococcal carriage and impact
      on otitis media are partly offset by concomitant increase of nonvaccine
      serotypes. We investigated in a randomized controlled trial the impact of 2-doses
      and 2+1-doses of PCV7(CRM197) on carriage of Streptococcus pneumoniae and of
      other nasopharyngeal commensals and well-known otitis media pathogens,
      Haemophilus influenzae and Moraxella catarrhalis, in children. Nasopharyngeal
      swabs were collected at the age of 6 weeks and at 6, 12, 18 and 24 months. We
      observed high carriage rates up to 68% for S. pneumoniae, 71% for H. influenzae
      and 68% for M. catarrhalis at the age of 18 months. Reduced dose (CRM197)
      schedules induced a slight reduction in overall pneumococcal carriage but no
      increases in the presence of H. influenzae and M. catarrhalis.

PMID- 21893152
TI  - Evaluation of dermal and eye irritation and skin sensitization due to carbon
      nanotubes.
AB  - The present paper summarizes the results of our studies on dermal and eye
      irritation and skin sensitization due to carbon nanotubes (CNTs), whose potential
      applications and uses are wide and varied, including CNT-enhanced plastics,
      electromagnetic interference/radio-frequency (EMI/RFI) shielding, antistatic
      material, flexible fibers and advanced polymers, medical and health applications,
      and scanning probe microscopy. Skin and eyes have the highest risk of exposure to
      nanomaterials, because deposition of nanomaterials to the surficial organs has
      the potential to be a major route of exposure during the manufacturing, use, and
      disposal of nanomaterials. Two products composed of single-walled carbon
      nanotubes (SWCNTs) and two products composed of multi-walled carbon nanotubes
      (MWCNTs) were tested regarding acute dermal and acute eye irritation using
      rabbits, and skin sensitization using guinea pigs. The concentrations of the CNTs
      in the substances were the maximum allowable for administration. The two products
      of SWCNTs and one of the products of MWCNTs were not irritants to the skin or
      eyes. The other product of MWCNTs caused very slight erythema at 24h, but not at
      72h, after patch removal in the dermal irritation experiments and conjunctival
      redness and blood vessel hyperemia at 1h, but not at 24h, in eye irritation
      experiments. These findings showed that one product of MWCNTs was a very weak
      acute irritant to the skin and eyes. No products of SWCNTs and MWCNTs exhibited
      skin-sensitization effects. Our knowledge of the toxicological effects of CNTs is
      still limited. Further information is needed to clarify the potential for
      irritation and sensitization given the complex nature of CNTs.

PMID- 21893153
TI  - Herbal hepatotoxicity by Greater Celandine (Chelidonium majus): causality
      assessment of 22 spontaneous reports.
AB  - Toxic liver injury due to the herb Greater Celandine (GC) (Chelidonium majus L.)
      has been assumed in patients originating from various European countries and
      created concern. Based on regulatory and liver unspecific ad hoc causality
      assessments in 22 spontaneous cases of Germany, causality levels for GC were
      considered probable in 16 and possible in 6 cases. We now analyzed the data of
      these 22 cases regarding their causality levels employing the liver specific,
      standardized, structured and quantitative assessment method of the updated scale
      of CIOMS (Council for International Organizations of Medical Sciences). Causality
      for GC was found highly probable (n=2), probable (n=6), possible (n=10), unlikely
      (n=1), and excluded (n=3). Thus, causality could be upgraded in 2 cases to a
      highly probable causality level, but had to be down graded to excluded, unlikely,
      or possible causality levels in 3, 1, or 9 cases, respectively. GC hepatotoxicity
      shows a hepatocellular pattern of liver injury with female gender predominance.
      On average, age of the patients was 56.4 years, treatment 36.4 days, and latency
      period until first symptoms and jaundice 29.8 and 35.6 days, respectively. This
      analysis therefore provides further evidence for the existence of GC
      hepatotoxicity as a distinct form of herb induced liver injury, but due to poor
      data quality the causal association between GC use and liver injury is less
      strong than hitherto assumed. We propose replacement of the regulatory organ
      unspecific by a liver specific causality assessment method in cases of herb
      induced liver injury as well as stricter pharmacovigilance strategies towards
      improvements of data quality. Toxicological studies are now warranted to
      elucidate the mechanism(s) of human GC hepatotoxicity that represents a European
      issue.

PMID- 21893154
TI  - The role of CRH in behavioral responses to acute restraint stress in zebrafish.
AB  - In teleosts, changes in swimming, exploring, general locomotor activity, and
      anxious state can be a response to stress mediated by the corticotropin-releasing
      hormone system activation and its effects on glucocorticoid levels. Zebrafish has
      been widely used to study neuropharmacology and has become a promising animal
      model to investigate neurobehavioral mechanisms of stress. In this report the
      animals were submitted to acute restraint stress for different time lengths (15,
      60 and 90 min) for further evaluation of behavioral patterns, whole-body cortisol
      content, and corticotropin-releasing hormone expression. The results demonstrated
      an increase in the locomotor activity and an alteration in the swimming pattern
      during a 5-min trial after the acute restraint stress. Interestingly, all groups
      of fish tested in the novel tank test exhibited signs of anxiety as evaluated by
      the time spent in the bottom of the tank. Whole-body cortisol content showed a
      positive correlation with increased behavioral indices of locomotion in zebrafish
      whereas molecular analysis of corticotropin-releasing hormone showed a late
      reduction of mRNA expression (90 min). Altogether, we present a model of acute
      restraint stress in zebrafish, confirmed by elevated cortisol content, as a valid
      and reliable model to study the biochemical basis of stress behavior, which seems
      to be accompanied by a negative feedback of corticotropin-release hormone mRNA
      expression.

PMID- 21893155
TI  - Differential programming of p53-deficient embryonic cells during rotenone block.
AB  - Mitochondrial dysfunction has been implicated in chemical toxicities. The present
      study used an in vitro model to investigate the differential expression of
      metabolic pathways during cellular stress in p53-efficient embryonic fibroblasts
      compared to p53-deficient cells. These cell lines differed with respect to
      NADH/NAD(+) balance. This ratio constitutes a driving force for NAD- and NADH
      dependent reactions and is inversed upon exposure to Rotenone (complex I
      inhibitor). Rotenone perturbed the structure of the elongated fibrillar tubulin
      network and decreased mRNA expression of tubulin genes both suggesting
      reprogramming and reorganization of the cytoskeleton in both cell lines. These
      changes were reflected in the abundance of specific mRNA and microRNA (miRNA)
      species as determined from genome-based analysis. Changes in mRNA and miRNA
      expression profiles reflected differences in energy utilizing pathways,
      consistent with the notion that the p53 pathway influences the cellular response
      to mitochondrial dysfunction and that at least some control may be embedded
      within specific mRNA/miRNA networks in embryonic cells.

PMID- 21893156
TI  - Oxazolone (OXA) is a respiratory allergen in Brown Norway rats.
AB  - Oxazolone (OXA) is a potent contact allergen in man, and it is used as a model
      Th1-allergen to test (Q)SAR's and screening assays for allergenic potential of
      chemicals. However, it elevates serum IgE levels and Thelper2 cytokines at
      relatively low doses in test animals, suggesting that it has also respiratory
      allergenic potential. The lack of human data on respiratory allergenic potential
      of OXA may be due to lack of significant inhalation exposure. Here, female Brown
      Norway rats (BN) were sensitized by two or five dermal applications of OXA at the
      same total dose of 3.75mg. Controls received vehicle. All animals were challenged
      by inhalation to 45mg/m(3) OXA on day 21 and necropsy was performed on day 22.
      All sensitized animals had increased serum IgE. OXA challenge decreased breathing
      frequency, and induced apnoeic breathing in the sensitized animals - a hallmark
      of respiratory allergy in our model. An exudative, granulocytic inflammation was
      observed primarily in the larynx of the sensitized and challenged rats.
      Microarray analysis of lung tissue, sampled 24h after challenge, revealed
      upregulation of several genes and activation of Gene Ontology (GO) pathways,
      which resembled more closely those found previously in lung tissue of rats
      sensitized and challenged by the respiratory allergen trimellitic anhydride than
      by the contact allergen dinitrochlorobenzene. The results indicate that the
      contact allergen OXA can also be a respiratory allergen, provided that it is
      inhaled. Its use as a model contact sensitizer must be reconsidered.

PMID- 21893157
TI  - Drastic changes in the tissue-specific expression of secreted phospholipases A2
      in chicken pulmonary disease.
AB  - Infectious bronchitis is one of the most important diseases in poultry and it
      causes major economic losses. Infectious bronchitis is an acute, highly
      contagious, viral disease of chickens, characterized by rales, coughing, and
      sneezing. Because secreted phospholipases A2 (sPLA2) are involved in inflammatory
      processes, the gene expressions of sPLA2s were investigated in both healthy
      chickens and chickens with infectious bronchitis and lung inflammation. The draft
      chicken genome was first scanned using human sPLA2 sequences to identify chicken
      sPLA2s (ChPLA2), chicken total mRNA were isolated and RT-PCR experiments were
      performed to amplify and then sequence orthologous cDNAs. Full-length cDNA
      sequences of ChPLA2-IB, -IIA, -IIE, -V and -X were cloned. The high degree of
      sequence identity of 50-70% between the avian and mammalian (human and mouse)
      sPLA2 orthologs suggests a conservation of important enzymatic functions for
      these phospholipases. Quantitation by qPCR of the transcript levels of ChPLA2-IB,
      -IIA, -IIE, -V and -X in several tissues from healthy chicken indicated that the
      expression patterns and mRNA levels diverged among the phospholipases tested. In
      chicken with infectious bronchitis, an over expression of ChPLA2-V was observed
      in lungs and spleen in comparison with healthy chicken. These findings suggest
      that ChPLA2-V could be a potential biomarker for lung inflammation. Conversely, a
      down regulation of ChPLA2-IB, -IIA and -X was observed in lungs and spleen in
      case of infectious bronchitis. A significant increase in the expression level of
      ChPLA2-X and ChPLA2-IB was also noticed in pancreas. No or minor changes have
      been detected in the expression of ChPLA2-IIE in lungs and small intestine, but
      it shows a significant increase in several infected tissues.

PMID- 21893159
TI  - DNA compaction by mononuclear platinum cancer drug cisplatin and the trisplatinum
      anticancer agent BBR3464: Differences and similarities.
AB  - Cisplatin, a mononuclear platinum compound, which is known as a cancer drug for
      long time, can exhibit considerable side effects and is also not effective in
      many types of cancer. Therefore, the alternative platinum anticancer agents that
      can act at a much lower dose limit compared to the dose relevant for cisplatin
      treatment have been searched for. BBR3464, a trinuclear platinum compound, is
      found to exhibit cytotoxic effects at 10 to 1000 times lower dose limit, even in
      cisplatin-resistant cancer cells. The primary cellular target for cisplatin and
      BBR3464 is thought to be DNA. Herein, we report the nature of DNA structural
      changes that are induced by cisplatin and BBR3464, considering the same DNA
      sequence and similar sample deposition methods for comparison purpose. We have
      applied high-resolution atomic force microscopy (AFM) in order to obtain an idea
      about the molecular basis of BBR3464's effectiveness at the lower dose limit. We
      show from the molecularly resolved AFM images that both the compounds can compact
      the whole dsDNA molecules, though the degree of compaction in case of BBR3464
      treatment is significantly higher. Furthermore, local compaction in terms of loop
      structure formation could be induced by both BBR3464 and cisplatin, though
      BBR3464 generated microloops and macroloops both, whereas cisplatin could
      generate primarily the microloops. It is a significant observation that BBR3464
      could induce relatively drastic DNA structural changes in terms of loop formation
      as well as overall DNA compaction at a molar ratio, which is 50 times less than
      that applied for cisplatin treatment. Implications of such structural changes in
      cytotoxic effects of the platinum anticancer agents will be mentioned.

PMID- 21893158
TI  - Identification of important residues in diketoreductase from Acinetobacter baylyi
      by molecular modeling and site-directed mutagenesis.
AB  - Diketoreductase (DKR) from Acinetobacter baylyi exhibits a unique property of
      double reduction of a beta, delta-diketo ester with excellent stereoselectivity,
      which can serve as an efficient biocatalyst for the preparation of an important
      chiral intermediate for cholesterol lowering statin drugs. Taken the advantage of
      high homology between DKR and human heart 3-hydroxyacyl-CoA dehydrogenase (HAD),
      a molecular model was created to compare the tertiary structures of DKR and HAD.
      In addition to the possible participation of His-143 in the enzyme catalysis by
      pH profile, three key amino acid residues, Ser-122, His-143 and Glu-155, were
      identified and mutated to explore the possibility of involving in the catalytic
      process. The catalytic activities for mutants S122A/C, H143A/K and E155Q were
      below detectable level, while their binding affinities to the diketo ester
      substrate and cofactor NADH did not change obviously. The experimental results
      were further supported by molecular docking, suggesting that Ser-122 and His-143
      were essential for the proton transfer to the carbonyl functional groups of the
      substrate. Moreover, Glu-155 was crucial for maintaining the proper orientation
      and protonation of the imidazole ring of His-143 for efficient catalysis.

PMID- 21893160
TI  - CD 38 expression, attachment style and habituation of arousal in relation to
      trust-related oxytocin release.
AB  - Oxytocin plays an important role in human attachment, trust, social perception,
      memory, and fear regulation. Evidence suggests that CD38, a regulator of oxytocin
      release, may also be critical in these processes. The purpose of this study was
      to investigate the predictors of plasma oxytocin level measured after a task
      requiring intimate trust (secret sharing), modeling psychotherapeutic processes,
      and a neutral social interaction. Results revealed that peripheral CD38
      expression positively predicted both trust-related and trust-unrelated oxytocin
      levels. In addition, habituation of arousal, as measured by skin conductance
      response, and attachment anxiety also emerged as predictors of oxytocin level in
      the trust-related condition. These results suggest that CD38 plays a general role
      in oxytocin secretion, whereas habituation of arousal and attachment anxiety are
      specifically related to situations involving intimate trust.

PMID- 21893161
TI  - Morphology of the external genitalia of the adult male and female mice as an
      endpoint of sex differentiation.
AB  - Adult external genitalia (ExG) are the endpoints of normal sex differentiation.
      Detailed morphometric analysis and comparison of adult mouse ExG has revealed 10
      homologous features distinguishing the penis and clitoris that define masculine
      vs. feminine sex differentiation. These features have enabled the construction of
      a simple metric to evaluate various intersex conditions in mutant or hormonally
      manipulated mice. This review focuses on the morphology of the adult mouse penis
      and clitoris through detailed analysis of histologic sections, scanning electron
      microscopy, and three-dimensional reconstruction. We also present previous
      results from evaluation of "non-traditional" mammals, such as the spotted hyena
      and wallaby to demonstrate the complex process of sex differentiation that
      involves not only androgen-dependent processes, but also estrogen-dependent and
      hormone-independent mechanisms.

PMID- 21893162
TI  - The expression and localization of Prune2 mRNA in the central nervous system.
AB  - A family of Bcl-2/adenovirus E1B 19kDa-interacting proteins (BNIPs) plays
      critical roles in several cellular processes such as cellular transformation,
      apoptosis, neuronal differentiation, and synaptic function, which are mediated by
      the BNIP2 and Cdc42GAP homology (BCH) domain. Prune homolog 2 (Drosophila)
      (PRUNE2) and its isoforms -C9orf65, BCH motif-containing molecule at the carboxyl
      terminal region 1 (BMCC1), and BNIP2 Extra Long (BNIPXL) - have been shown to be
      a susceptibility gene for Alzheimer's disease, a biomarker for leiomyosarcomas, a
      proapoptotic protein in neuronal cells, and an antagonist of cellular
      transformation, respectively. However, precise localization of PRUNE2 in the
      brain remains unclear. Here, we identified the distribution of Prune2 mRNA in the
      adult mouse brain. Prune2 mRNA is predominantly expressed in the neurons of the
      cranial nerve motor nuclei and the motor neurons of the spinal cord. The
      expression in the dorsal root ganglia (DRG) is consistent with the previously
      described reports. In addition, we observed the expression in another sensory
      neuron in the mesencephalic trigeminal nucleus. These results suggest that Prune2
      may be functional in these restricted brain regions.

PMID- 21893163
TI  - Central AMP-activated protein kinase affects sympathetic nerve activity in rats.
AB  - In this study, we examined the effect of intracerebroventricular (ICV) injection
      of 5-aminoimidazole-4-carboxamide 1-beta-d-ribofuranoside (AICAR), an AMP
      activated protein kinase (AMPK) activator, or compound C (CC), an AMPK inhibitor,
      on the activity of sympathetic nerves innervating the adrenal gland and kidney in
      urethane-anesthetized rats to elucidate the role of AMPK in sympathetic nervous
      system function. We found that an ICV injection of AICAR or CC significantly
      stimulated renal sympathetic nerve activity (RSNA) and adrenal sympathetic nerve
      activity (ASNA) in a dose-dependent manner. Following this, we examined the role
      of AMPK on the sympatho-excitation caused by leptin injection. Pretreatment with
      AICAR or CC eliminated the leptin-induced increase in RSNA, however, neither
      pretreatment with AICAR or CC affected the leptin-induced increase in ASNA. Our
      data suggest that AMPK may regulate the sympathetic nerve system, and that the
      stimulating effect of leptin on sympathetic nerve activity in kidney may depend
      on central AMPK.

PMID- 21893164
TI  - Importance of central AT1 receptors for sodium intake induced by GABAergic
      activation of the lateral parabrachial nucleus.
AB  - The blockade of the inhibitory mechanisms for sodium intake with GABAergic
      activation in the lateral parabrachial nucleus (LPBN) induces strong ingestion of
      water and hypertonic NaCl in satiated and normovolemic rats. A question that
      remains is if the activity of facilitatory mechanisms, like angiotensin II, is
      necessary for sodium and water intake induced by muscimol (GABA(A) receptor
      agonist) injected into the LPBN. Therefore, in the present study, we investigated
      the effects of the blockade of angiotensinergic AT(1) receptors with losartan
      injected i.c.v. on 0.3 M NaCl and water intake induced by muscimol injected into
      the LPBN in satiated and normovolemic rats. Male Holtzman rats with stainless
      steel cannulas implanted bilaterally into the LPBN and unilaterally into the
      lateral ventricle were used. Bilateral injections of muscimol (0.5 nmol/0.2 MUl)
      into the LPBN combined with i.c.v. injection of vehicle induced 0.3 M NaCl (31.7
      +/- 1.8 ml/240 min, vs. saline: 0.4 +/- 0.3 ml/240 min) and water intake (21.5 +/
      1.9 ml/240 min, vs. saline: 0.8 +/- 0.2 ml/240 min). Losartan (50 and 100
      MUg/1.0 MUl) injected i.c.v. reduced the effects of LPBN-muscimol on 0.3 M NaCl
      (18.9 +/- 1.9 and 9.9 +/- 1.7 ml/240 min, respectively) and water intake (9.8 +/-
      1.7 and 5.1 +/- 1.1 ml/240 min, respectively). The results suggest that the
      activation of central AT(1) angiotensinergic receptors is essential for
      hypertonic NaCl and water intake induced by the blockade of the inhibitory
      mechanisms with muscimol injected into the LPBN in satiated and normovolemic
      rats.

PMID- 21893165
TI  - Exercise affects memory acquisition, anxiety-like symptoms and activity of
      membrane-bound enzyme in brain of rats fed with different dietary fats:
      impairments of trans fat.
AB  - Here we evaluated the influence of physical exercise on behavior parameters and
      enzymatic status of rats supplemented with different dietary fatty acids (FA).
      Male Wistar rats fed diets enriched with soybean oil (SO), lard (L), or
      hydrogenated vegetable fat (HVF) for 48 weeks were submitted to swimming (30
      min/d, five times per week) for 90 days. Dietary FA per se did not cause anxiety
      like symptoms in the animals, but after physical exercise, SO group showed a
      better behavioral performance than L and the HVF groups in elevated plus maze
      (EPM). In Barnes maze, HVF group showed impaired memory acquisition as compared
      to L group, and exercise reversed this effect. SO-fed rats showed an improvement
      in memory acquisition after 1 day of training, whereas lard caused an improvement
      of memory only from day 4. HVF-fed rats showed no improvement of memory
      acquisition, but this effect was reversed by exercise in all training days. A
      lower activity of the Na(+)K(+)-ATPase in brain cortex of rats fed lard and HVF
      was observed, and this effect was maintained after exercise. Similarly, the HVF
      diet was related to lower activity of hippocampal Na(+)K(+)-ATPase, and exercise
      reduced activity of this enzyme in the SO and L groups. Our findings show
      influences of dietary FA on memory acquisition, whereas regular exercise improved
      this function and was beneficial on anxiety-like symptoms. As FA are present in
      neuronal membrane phospholipids and play a critical role in brain function, our
      results suggest that low incorporation of trans FA in neuronal membranes may act
      on cortical and hippocampal Na(+)K(+)-ATPase activity, but this change appears to
      be unrelated to the behavioral parameters primarily harmed by consumption of
      trans and less so by saturated FA, which were reversed by exercise.

PMID- 21893166
TI  - Natural and engineered coding variation in antidepressant-sensitive serotonin
      transporters.
AB  - The presynaptic serotonin (5-HT) transporter (SERT) is a key regulator of 5-HT
      signaling and is a major target for antidepressant medications and
      psychostimulants. In recent years, studies of natural and engineered genetic
      variation in SERT have provided new opportunities to understand structural
      dimensions of drug interactions and regulation of the transporter, to explore 5
      HT contributions to antidepressant action, and to assess the impact of SERT
      mediated 5-HT contributions to neuropsychiatric disorders. Here we review three
      examples from our recent studies where genetic changes in SERT, identified or
      engineered, have led to new models, findings, and theories that cast light on new
      dimensions of 5-HT action in the CNS and periphery. First, we review our work to
      identify specific residues through which SERT recognizes antagonists, and the
      conversion of this knowledge to the creation of mice lacking high-affinity
      antidepressant and cocaine sensitivity. Second, we discuss our studies of
      functional coding variation in SERT that exists in commonly used strains of
      inbred mice, and how this variation is beginning to reveal novel 5-HT-associated
      phenotypes. Third, we review our identification and functional characterization
      of multiple, hyperactive SERT coding variants in subjects with autism. Each of
      these activities has driven the development of new model systems that can be
      further exploited to understand the contribution of 5-HT signaling to risk for
      neuropsychiatric disorders and their treatment.

PMID- 21893167
TI  - Role of the endocannabinoid system in regulating glucocorticoid effects on memory
      for emotional experiences.
AB  - Glucocorticoids, stress hormones released from the adrenal cortex, have potent
      modulatory effects on emotional memory. Whereas early studies focused mostly on
      the detrimental effects of chronic stress and glucocorticoid exposure on
      cognitive performance and the classic genomic pathways that mediate these
      effects, recent findings indicate that glucocorticoids exert complex and often
      rapid influences on distinct memory phases. Specifically, glucocorticoids have
      been shown to enhance memory consolidation of emotionally arousing experiences,
      but to impair memory retrieval and working memory during emotionally arousing
      test situations. Furthermore, growing evidence indicates that these different
      glucocorticoid effects depend on a nongenomically mediated interaction with
      emotional arousal-induced noradrenergic activation within the basolateral complex
      of the amygdala. In this paper, we present a model suggesting that the
      endocannabinoid system, a lipid-based retrograde signaling system, might play an
      important role in mediating such rapid glucocorticoid influences on the
      noradrenergic system in modulating memory of emotionally arousing experiences.

PMID- 21893168
TI  - Low-frequency stimulation of bilateral anterior nucleus of thalamus inhibits
      amygdale-kindled seizures in rats.
AB  - Brain stimulation with low-frequency is emerging as an alternative treatment for
      refractory epilepsy. The anterior nucleus thalamus (ANT) is thought to be a key
      structure in the circuits of seizure generation and propagation. The present
      study aimed to investigate the effects of low frequency stimulation (LFS)
      targeting ANT on amygdala-kindled seizures in Sprague-Dawley rats. Electrodes
      were implanted into the right basolateral amygdala and the right or bilateral ANT
      of Sprague-Dawley rats. When fully kindled seizures were achieved by daily
      electrical stimulation of the amygdala, LFS (15 min train of 0.1 ms pulses at 1
      Hz and 200-500 MUA) was applied to the unilateral or bilateral ANT immediately
      before the kindling stimulation (pre-treatment). Our study showed that LFS of the
      bilateral ANT significantly decreased the incidence of generalized seizures (GS)
      and seizure stage, as well as shortened duration of afterdischarge and GS
      demonstrating an inhibition of the severity of seizures. Moreover, LFS elevated
      the afterdischarge threshold (ADT) and GS threshold indicating an inhibition of
      susceptibility to seizures. On the other hand, LFS of the unilateral ANT failed
      to show any significance in inhibiting seizures. Our study demonstrated that
      bilateral LFS in ANT could significantly inhibit amygdala-kindled seizures by
      preventing both afterdischarge generation and propagation. It provided further
      evidence for clinical use of LFS in ANT.

PMID- 21893169
TI  - Low frequency electroacupuncture selectively decreases voluntarily ethanol intake
      in rats.
AB  - Although there is increasing clinical acceptance of acupuncture and
      electroacupuncture (EA) as a treatment of substance abuse-related disorders, our
      understanding of this treatment remains incomplete. Previous clinical and pre
      clinical studies have shown that acupuncture and EA are effective in reducing
      ethanol consumption. Recent studies have shown that Sprague-Dawley (SD) rats
      under an intermittent-access two-bottle choice drinking procedure (IE procedure)
      voluntarily drank high amounts of ethanol. However, an effect of EA on ethanol
      consumption of the SD rats under this drinking procedure has not been
      demonstrated. In the present study, we demonstrated that SD rats escalated their
      ethanol intake and subsequently developed ethanol dependence under the IE
      procedure. A single low (2 Hz), but not high frequency (100 Hz) EA treatment
      applied at the bilateral acupoint Zusanli (ST36), but not at the tail reduced
      voluntary intake of, and preference for ethanol, but not sucrose. Furthermore,
      repeated EA treatments decreased the intake of and preference for ethanol,
      without resulting in a rebound increase in ethanol intake when the EA treatments
      were terminated. These observations indicate that EA may be a useful treatment
      for alcohol abuse.

PMID- 21893170
TI  - Maternal infection during late pregnancy increases anxiety- and depression-like
      behaviors with increasing age in male offspring.
AB  - Scientific reports suggest that the exposure to long-term stressors throughout or
      during late gestation increase anxiety- and depression-like behaviors of
      offspring in their later life. Moreover, several studies concluded that
      increasing age correlates with increased anxiety behaviors in humans and rodents.
      In the present study, we assessed the effects of prenatally administration of
      equal lipopolysaccharide (LPS) doses in various points of late gestation (days
      15, 16, and 17) period, on neuroendocrine and immunological responses of pregnant
      mice, and subsequent long-lasting consequences of anxiety and depression with
      increasing age in male offspring at postnatal days (PD) 40 and 80. Four hours
      after the LPS injection, levels of corticosterone (COR) and pro-inflammatory
      cytokines (PIC) in pregnant mice, as compared to the control dams, were increased
      significantly. Furthermore, maternal inflammation raised the levels of COR,
      anxiety- and depression-like behaviors with increasing age in male offspring in
      comparison with saline male offspring. These data support other studies
      demonstrating that maternal stress increases the levels of anxiety and depression
      in offspring. Additionally, our data confirm other findings indicating that
      increasing age correlates with increased anxiety or depression behaviors in
      humans and rodents. Findings of this study suggest that time course of an
      inflammation response or stressor application during various stages of gestation
      and ages of offspring are important factors for assessing neuropsychiatric
      disorders.

PMID- 21893171
TI  - Endothelium-independent effects of phyllanthin and hypophyllanthin on vascular
      tension.
AB  - The purpose of this study was to investigate the modulating effects of
      phyllanthin and hypophyllanthin on vascular tension, using in the in vitro model
      of isolated rat aorta. Our results indicated that both phyllanthin and
      hypophyllanthin significantly relaxed the sustained contraction induced by
      phenylephrine (PE) in a concentration-dependent manner. In addition, endothelial
      removal had no significant influence on the vasorelaxation responses of the
      aortic rings toward these two compounds. Furthermore, both compounds inhibited
      the contraction of aortic muscle provoked by either PE (1 MUM) or KCl (40 mM) as
      well as the spontaneous contraction of the Ca2+-depleted muscle. In high K+-Ca2+
      free solution, phyllanthin (100 MUM), but not hypophyllanthin, significantly
      inhibited the contractile responses upon cumulative addition of CaCl2. Both
      compounds (100 MUM) significantly inhibited PE-induced contraction in Ca2+-free
      condition, but could not affect caffeine-induced contraction. Taken together,
      phyllanthin and hypophyllanthin could modulate the vascular tension via the
      endothelium-independent mechanisms. The modulating effects of both compounds were
      possibly involved with the blockade of Ca2+ entry into vascular smooth muscle
      cells and inhibition of PE-mediated Ca2+ release from sarcoplasmic reticulum.

PMID- 21893172
TI  - A new biphenyl and antimicrobial activity of extracts and compounds from Clusia
      burlemarxii.
AB  - Phytochemical investigation on Clusia burlemarxii (Clusiaceae) led to isolation
      and identification of nine compounds. Were isolated from leaves 3-O-alpha-L-
      rhamnopyranosylquercetin, 3-O-alpha-L-rhamnopyranosylkaempferol, 4-hydroxy-5,5
      dimethyldihydrofuran-2-one, 2Z-delta-tocotrienoloic acid and friedelin and were
      isolated from trunk betulinic acid, protocatechuic acid, lyoniresinol, and a new
      biphenyl 2,2-dimethyl-3,5-dihydroxy-7-(4-hydroxyphenyl)chromane. The structures
      were determined by 1H, 13C-NMR, DEPT, HMBC, HMQC, HRESIMS. The Minimal Inhibitory
      Concentration against Streptococcus mutans, Staphylococcus aureus, Bacillus
      subtilis, Micrococcus luteus, Escherichia coli, Salmonella choleraesuis,
      Pseudomonas aeruginosa, Aspergillus niger and Cladosporium cladosporioides was
      also determined. Extracts and compounds showed significant activity against
      tested Gram-positive bacteria, none activity against tested Gram-negative
      bacteria and fungi.

PMID- 21893174
TI  - Multiple cis-elements in the 5'-flanking region of embryonic/larval fast-type of
      the myosin heavy chain gene of torafugu, MYH(M743-2), function in the
      transcriptional regulation of its expression.
AB  - The myosin heavy chain gene, MYH(M743-2), is highly expressed in fast muscle
      fibers of torafugu embryos and larvae, suggesting its functional roles for
      embryonic and larval muscle development. However, the transcriptional regulatory
      mechanism involved in its expression remained unknown. Here, we analyzed the
      2075bp 5'-flanking region of torafugu MYH(M743-2) to examine the spatial and
      temporal regulation by using transgenic and transient expression techniques in
      zebrafish embryos. Combining both transient and transgenic analyses, we
      demonstrated that the 2075bp 5'-flanking sequences was sufficient for its
      expression in skeletal, craniofacial and pectoral fin muscles. The
      immunohistochemical observation revealed that the zebrafish larvae from the
      stable transgenic line consistently expressed enhanced green fluorescent protein
      (EGFP) in fast muscle fibers. Promoter deletion analyses demonstrated that the
      minimum 468bp promoter region could direct MYH(M743-2) expression in zebrafish
      larvae. We discovered that the serum response factor (SRF)-like binding sites are
      required for promoting MYH(M743-2) expression and myoblast determining factor
      (MyoD) and myocyte enhancer factor-2 (MEF2) binding sites participate in the
      transcriptional control of MYH(M743-2) expression in fast skeletal muscles. We
      further discovered that MyoD binding sites, but not MEF2, participate in the
      transcriptional regulation of MYH(M743-2) expression in pectoral fin and
      craniofacial muscles. These results clearly demonstrated that multiple cis
      elements in the 5'-flanking region of MYH(M743-2) function in the transcriptional
      control of its expression.

PMID- 21893173
TI  - RNA polymerase I activity is regulated at multiple steps in the transcription
      cycle: recent insights into factors that influence transcription elongation.
AB  - Synthesis of the translation apparatus is a central activity in growing and/or
      proliferating cells. Because of its fundamental importance and direct connection
      to cell proliferation, ribosome synthesis has been a focus of ongoing research
      for several decades. As a consequence, much is known about the essential factors
      involved in this process. Many studies have shown that transcription of the
      ribosomal DNA by RNA polymerase I is a major target for cellular regulation of
      ribosome synthesis rates. The initiation of transcription by RNA polymerase I has
      been implicated as a regulatory target, however, recent studies suggest that the
      elongation step in transcription is also influenced and regulated by trans-acting
      factors. This review describes the factors required for rRNA synthesis and
      focuses on recent works that have begun to identify and characterize factors that
      influence transcription elongation by RNA polymerase I and its regulation.

PMID- 21893175
TI  - Simultaneous determination of five synthetic pyrethroid metabolites in urine by
      liquid chromatography-tandem mass spectrometry: application to 39 persons without
      known exposure to pyrethroids.
AB  - A sensitive and reliable method was developed and validated for the determination
      of five synthetic pyrethroid metabolites namely cis-Cl(2)CA, trans-Cl(2)CA,
      Br(2)CA, 3-PBA and 4-FPBA in human urine by liquid chromatography-tandem mass
      spectrometry. (2)D(6)-labelled trans-Cl(2)CA and (13)C(6)-labelled 3-PBA were
      used as internal standards. This method was based on a liquid-liquid extraction
      procedure in acidic conditions using hexane solvent with a basic purification, a
      chromatographic separation using a specific C18 column and mass spectrometric
      detection in the negative polarity. Suitable limits of detection (0.015MUg/L for
      the five compounds) and quantification (from 0.020 to 0.030MUg/L) were obtained
      for rendering the method usable for the biomonitoring of pyrethroids in the
      general population. The efficiency of the method was tested in 39 urine samples
      from French people without any known exposure to pyrethroids. At least three of
      the five metabolites were detected in each sample. The results of this study were
      compared to those obtained in previous ones and discussed.

PMID- 21893176
TI  - In vitro and in ovo effects of four brominated flame retardants on toxicity and
      hepatic mRNA expression in chicken embryos.
AB  - Some currently used brominated flame retardants (BFRs), such as
      hexachlorocyclopentadienyl-dibromocyclooctane (HCDBCO), bis(2
      ethylhexyl)tetrabromophthalate (BEHTBP), 1,2-bis(2,4,6-tribromophenoxy)ethane
      (BTBPE) and decabromodiphenylethane (DBDPE), are persistent organic contaminants
      detected in various environmental matrices, including wild birds. Data on
      potential toxicological and molecular responses to exposure of these BFRs are
      lacking for avian species. A combined in vitro/in ovo approach was used to
      determine the concentration-dependent effects of these BFRs on overt toxicity and
      hepatic messenger RNA (mRNA) expression levels of 11 transcripts in (1) primary
      cultures of chicken embryonic hepatocytes (CEH; all four BFRs) and (2) chicken
      embryos (HCDBCO and BTBPE only). Neither hepatocyte viability nor embryonic
      pipping success were affected by the BFRs at any of the administered
      concentrations (CEH: 0.001-30 MUM, egg injection: 0.1-10 MUg/g nominal dose). In
      CEH, 10 MUM HCDBCO induced cytochrome P450 2H1 (CYP2H1) and CYP3A37, while
      CYP1A4/5 were down-regulated at all tested concentrations. In contrast, only
      transthyretin was down-regulated by HCDBCO in embryonic liver. There was
      concordance between the BTBPE-induced transcriptional responses in vitro and in
      ovo for CYP1A4/5 (up-regulated) and type III iodothyronine 5'-deiodinase (DIO3;
      down-regulated). DBDPE induced CYP1A4/5 29- and 59-fold at 0.2 MUM in CEH and
      increased DIO1. None of the gene targets were responsive to BEHTBP exposure in
      CEH. The multi-tiered in vitro/in ovo screening approach was effective for
      assessing toxicological and molecular biological effects of these BFRs in an
      avian species.

PMID- 21893177
TI  - Estrogen agonist/antagonist properties of dibenzyl phthalate (DBzP) based on in
      vitro and in vivo assays.
AB  - The most commonly used phthalates have been banned or restricted for use as
      plasticizers in toys in some countries because of their endocrine-disrupting
      properties. Dibenzyl phthalate (DBzP) has been proposed as a possible alternative
      for the banned/restricted phthalates. In this study, the estrogen
      agonist/antagonist properties of DBzP were predicted by molecular docking and
      confirmed by yeast estrogen screen (YES) and immature mouse uterotrophic assays.
      The YES assay results showed a dose-dependent increase in DBzP estrogen agonist
      activity from 10-6 to 10-4 M, and at concentrations from 1.95*10-6 M to higher,
      DBzP significantly inhibited the agonist activity of 10-9 M 17beta-estradiol
      (E2), inhibiting 10-9 M E2 by 74.5% at its maximum effectiveness. The in vivo
      estrogen agonist/antagonist activities of DBzP were demonstrated in immature
      mouse uterotrophic assays. The antagonist activity of DBzP inhibited E2-induced
      uterine growth promoted at 40 and 400 MUg/kg bw (body weight) (P<0.05). In
      addition, we also analyzed the estrogen agonist/antagonist potentials of benzyl
      butyl phthalate (BBP) by YES, and found both were weaker than those of DBzP,
      suggesting DBzP would be more toxic than BBP and should not be used as an
      alternative plasticizer.

PMID- 21893178
TI  - Reducible HPMA-co-oligolysine copolymers for nucleic acid delivery.
AB  - Biodegradability can be incorporated into cationic polymers via use of disulfide
      linkages that are degraded in the reducing environment of the cell cytosol. In
      this work, N-(2-hydroxypropyl)methacrylamide (HPMA) and methacrylamido
      functionalized oligo-l-lysine peptide monomers with either a non-reducible 6
      aminohexanoic acid (AHX) linker or a reducible 3-[(2-aminoethyl)dithiol]
      propionic acid (AEDP) linker were copolymerized via reversible addition
      fragmentation chain transfer (RAFT) polymerization. Both of the copolymers and a
      1:1 (w/w) mixture of copolymers with reducible and non-reducible peptides were
      complexed with DNA to form polyplexes. The polyplexes were tested for salt
      stability, transfection efficiency, and cytotoxicity. The HPMA-oligolysine
      copolymer containing the reducible AEDP linkers was less efficient at
      transfection than the non-reducible polymer and was prone to flocculation in
      saline and serum-containing conditions, but was also not cytotoxic at charge
      ratios tested. Optimal transfection efficiency and toxicity were attained with
      mixed formulation of copolymers. Flow cytometry uptake studies indicated that
      blocking extracellular thiols did not restore transfection efficiency and that
      the decreased transfection of the reducible polyplex is therefore not primarily
      caused by extracellular polymer reduction by free thiols. The decrease in
      transfection efficiency of the reducible polymers could be partially mitigated by
      the addition of low concentrations of EDTA to prevent metal-catalyzed oxidation
      of reduced polymers.

PMID- 21893179
TI  - Lipid nanoparticle purification by spin centrifugation-dialysis (SCD): a facile
      and high-throughput approach for small scale preparation of siRNA-lipid
      complexes.
AB  - This paper describes the use of spin centrifugation-dialysis (SCD) for small
      scale concentration/purification of siRNA-lipid complexes designed for use as
      therapeutic agents for gene silencing. SCD consists of a two-step method for
      concentration, filtration and buffer exchange of lipid nanoparticles (LNP) to
      provide a homogeneous preparation suitable for injection. Here, we compare SCD
      with the more traditionally used tangential flow filtration (TFF), and
      demonstrate the physicochemical and biological comparability of LNPs produced
      with both methods. TFF is a highly scalable method used in both developmental and
      production applications, but is limited in terms of miniaturization. In contrast
      to TFF, SCD is faster, less expensive, and requires less oversight for assembling
      LNPs for small-scale applications, such as target screening both in vitro and in
      vivo. The finding that SCD is a viable method for filtering LNPs in a manner
      similar to TFF, producing particles with comparable properties and biological
      activity, is significant given the complexity and sensitivity of LNPs to
      processing conditions.

PMID- 21893180
TI  - Short multi-armed polylysine-graft-polyamidoamine copolymer as efficient gene
      vectors.
AB  - Polyamidoamine-polylysine graft copolymers (PAMAM-g-PLL) were prepared by ring
      opening polymerization of benzyloxycarbonyl lysine N-carboxyanhydride (Lys(Z)
      NCA) initiated with primary amine of generation 4 polyamidoamine (PAMAM G4) and
      subsequent deprotection of polyamidoamine-poly-(benzyloxycarbonyl lysine)
      copolymer (PAMAM-PLL(Z)). The chemical structure and composition of the PAMAM-g
      PLL with varying length of PLL arms were characterized by Fourier transform
      infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy ((1)H
      NMR). Agarose gel electrophoresis test revealed that the PAMAM-g-PLL could
      completely combine DNA to form complexes. The scanning electronic microscopy
      (SEM) and atomic force microscopy (AFM) observation showed that the morphology of
      these complexes was spherical. Dynamic light scattering (DLS) measurement
      illustrated that the sizes of complexes were in range of 100-200 nm. The MTT
      assay demonstrated that cytotoxicity of PAMAM-g-PLL were lower than the either
      PAMAM G4 or the poly-L-lysine-15k (PLL-15k). The in vitro transfection test
      indicated that the PAMAM-g-PLL with 3.8 average polymerization degrees of PLL
      arms (PAMAM-PLL-3.8) displayed significantly higher transfection efficiency than
      that of PAMAM G4 and PLL-15k at the same N/P ratio, Furthermore, PAMAM-PLL-3.8 at
      the N/P of 40 or 80 displayed better serum-resistant capability than that of PEI
      25k and Lipofectamine 2000. The DNA local delivery test in rabbit vessel
      exhibited that the restenosis was inhibited to a significant extent. The above
      facts revealed that PAMAM-PLL-3.8 is a promising gene vector with low
      cytotoxicity, high transfection efficiency and serum-resistant ability.

PMID- 21893181
TI  - Variable degrees of hearing impairment in a Dutch DFNX4 (DFN6) family.
AB  - OBJECTIVE: Investigation of the audiometric characteristics of a large Dutch
      DFNX4 family with a p.Glu72X mutation in the SMPX gene. PATIENTS AND METHODS:
      Sixty family members participated in this study and examination consisted of
      medical history, otoscopy, pure tone and speech audiometry. Linkage and mutation
      analysis revealed a pathogenic mutation in the SMPX gene. RESULTS: All 25
      mutation carriers exhibited hearing impairment, except one woman aged 25 years.
      The men (n = 10) showed more severe hearing impairment than the women (n = 14)
      and already at a younger age. The age of onset according to history was 2-10
      years (mean: 3.3 years) in men and 3-48 years (mean: 26.4 years) in women. In the
      men, severe threshold deterioration mainly occurred during the first two decades
      of life, especially at the higher frequencies. The women showed milder threshold
      deterioration and more pronounced across-subjects and individual inter-aural
      variation, especially at 2-8 kHz. Longitudinal linear regression analysis
      demonstrated significant progression of at least two frequencies in five
      individuals (3 men and 2 women). The speech recognition scores of the mutation
      carriers with hearing impairment were decreased at relatively young ages compared
      to a reference group of patients with only presbycusis, especially in men.
      However, all these patients tended to have better speech recognition scores than
      the presbycusis patients at matching PTA(1,2,4 kHz) levels. CONCLUSION: This
      study demonstrates the phenotypic heterogeneity in this large family with an X
      linked pattern of inherited sensorineural hearing impairment. The men showed more
      severe hearing impairment at a younger age with more pronounced progression
      during the first two decades of life, while women demonstrated less severe
      hearing impairment with more gradual progression and a wider variation in age of
      onset, degree of hearing impairment and inter-aural asymmetry in thresholds.

PMID- 21893182
TI  - Anti-inflammatory, analgesic and antipyretic properties of Thespesia populnea
      Soland ex. Correa seed extracts and its fractions in animal models.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Thespesia populnea Sol. ex Correa (Malvaceae) is
      commonly known as "Indian tulip tree". The plant has been used as an astringent,
      antibacterial, anti-inflammatory, antinociceptive and hepatoprotective in Indian
      system of traditional medicine. MATERIALS AND METHODS: Thespesia populnea seeds
      were successively extracted by soxhlet extraction using petroleum ether (40-60 
      degrees C) (TPO) and ethanol (TPE). Unsaponifiable matter (TPOUM) and fatty acids
      were separated from seed oil. A GC-MS analysis of fatty acid methyl esters was
      carried out. Ethanolic extract was fractionated using CHCl(3), EtOAc, n-BuOH and
      H(2)O. Acute arthritis was induced by sub-plantar injection of carrageenan into
      the left hind paw of rats. The paw volume was measured using plethysmometer.
      Analgesic activity was assessed by heat induced pains (tail immersion model) and
      antipyretic activity assessed using brewers yeast-induced pyrexia model. RESULTS:
      Oral administration of TPO and TPE at 200 and 400 mg/kg b.w. and tested fractions
      at 200mg/kg significantly reduced carrageenan induced paw edema and brewers yeast
      induced pyrexia. In tail immersion method also extracts and fractions showed
      significant analgesic activity. Amongst all fractions EtOAc showed most
      significant results. TPOUM showed significant anti-inflammatory and analgesic
      activity. GC-MS analyses showed the presence of fourteen fatty acids, predominant
      fatty acids were palmitic and stearic acid. CONCLUSION: These results highlighted
      anti-inflammatory, analgesic and antipyretic effects of Thespesia populnea seeds.

PMID- 21893183
TI  - An ethnobotanical survey of mosquito repellent plants in uMkhanyakude district,
      KwaZulu-Natal province, South Africa.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: The aim of the study was to document plants
      traditionally used to repel mosquitoes in the uMkhanyakude district, KwaZulu
      Natal, South Africa. The specific objectives of the study were to: (1) identify
      plant species and their parts being used; (2) determine the condition of plant
      material used and the method of application. MATERIALS AND METHODS: Data was
      collected from 60 respondents in five villages in the district using standardised
      and pre-tested questionnaires. RESULTS: Thirteen plant species are used in the
      study area to repel mosquitoes. These species belong to 11 genera from 9
      families. Meliaceae and Anacardiaceae were the most represented families with two
      species each. The most frequently recorded species were Lippia javanica (91.67%),
      followed by Aloe ferox (11.67%), Sclerocarya birrea (5%), Melia azedarach (3%),
      Balanite maughamii (3%) and Mangifera indica (3%). Leaves were the most (38%)
      common plant part used. The majority (82%) of the plant parts were used in a dry
      state. Burning of plant materials to make smoke was the most (92%) common method
      of application. Nine plant species, namely: A. ferox, Calausena anista, Croton
      menyharthii, S. birrea, B. maughamii, Olax dissitiflora, Trichilia emetic, M.
      indica, and Atalaya alata are documented for the first time as mosquito
      repellents. CONCLUSION: This documentation provides the basis for further studies
      in developing new, effective, safe and affordable plant-derived mosquito
      repellents especially for Africa where malaria is highly prevalent. The study
      also plays a part in documenting and conserving traditional knowledge of mosquito
      repellent plants for future use.

PMID- 21893184
TI  - The cardioprotective effects of marrubiin, a diterpenoid found in Leonotis
      leonurus extracts.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Leonotis leonurus L. (Lamiaceae) is used as a
      traditional medicine for a variety of ailments in South Africa. The diterpene
      marrubiin is the major product constituent in specimens of this plant occurring
      in South Africa. MATERIALS AND METHODS: Marrubiin isolated from South African
      specimens of L. leonurus in addition to an organic extract of L. leonurus were
      tested in vivo, ex vivo and in vitro for their anticoagulant, antiplatelet and
      anti-inflammatory activities. RESULTS: Marrubiin and the organic extract
      suppressed coagulation, platelet aggregation and inflammatory markers. For the
      coagulation markers it was found that the organic extract and marrubiin
      significantly prolonged activated partial thromboplastin time (APTT). Fibrin and
      D-dimer formation were drastically decreased. These findings were observed in an
      ex vivo model and an obese rat model. Chemokines enhance leukocyte recruitment to
      inflammatory sites. TNF-alpha and RANTES secretion were significantly reduced by
      the extract and marrubiin when determined in the obese rat model relative to the
      controls. Calcium mobilization and TXB(2) synthesis were suppressed by the
      extract and marrubiin. An in vitro model was used to elucidate the antiplatelet
      mechanism and it was found that the extract and marrubiin inhibited platelet
      aggregation by inhibiting the binding of fibrinogen to glycoprotein (GP) IIb/IIIa
      receptor in a concentration dependent manner. CONCLUSION: The findings reflect
      that marrubiin largely contributes to the extract's anticoagulant, antiplatelet
      and anti-inflammatory effects observed.

PMID- 21893185
TI  - Hepatoprotective effects and mechanisms of dehydrocavidine in rats with carbon
      tetrachloride-induced hepatic fibrosis.
AB  - AIM OF THE STUDY: The current study was designed to examine the effects and
      possible mechanisms of dehydrocavidine (DC) on carbon tetrachloride (CCl4)
      induced hepatic fibrosis in male Sprague-Dawley (SD) rats. MATERIALS AND METHODS:
      Hepatic fibrosis was induced in male rats with CCl4 administration for 12 weeks.
      Liver histopathological study was performed, and the liver function was examined
      by determining the serum alanine aminotransferase (ALT), aspartate
      aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH)
      and total bilirubin (TBIL) for evaluating the effect of DC on hepatic fibrosis.
      The possible mechanisms were investigated by measuring hepatic collagen
      metabolism and oxidative stress level. Furthermore, oligo microarray analysis of
      263 genes was performed, and quantitative real-time RT-PCR was used to verify 4
      of the abnormally expressed genes (Bcl2, Cyp3a13, IL18 and Rad50). RESULTS: DC
      treatment significantly inhibited the loss of body weight and the increase of
      liver weight induced by CCl4. DC also improved the liver function of rats as
      indicated by decreased serum enzymatic activities of ALT, AST, ALP and TBIL.
      Histopathological results indicated that DC alleviated liver damage and reduced
      the formation of fibrous septa. Moreover, DC significantly decreased liver
      hydroxyproline (Hyp) and increased urine Hyp. It also decreased liver
      malondialdehyde concentration, increased activities of liver superoxide
      dismutase, catalase and glutathione peroxidase. Microarray analysis revealed that
      DC altered the expression of genes related to apoptosis, cytokines and other
      proteins involved in tissue repair. CONCLUSIONS: Our findings indicate that DC
      can protect rats from CCl4-induced hepatic fibrosis through reducing oxidative
      stress, promoting collagenolysis, and regulating fibrosis-related genes.

PMID- 21893186
TI  - Anti-hypoxic activity at simulated high altitude was isolated in petroleum ether
      extract of Saussurea involucrata.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rhodiola algida, Saussurea involucrata, and other
      herbs grown in Qinghai-Tibetan plateau have long been used to prevent and treat
      acute mountain sickness. AIM OF THE STUDY: To screen and identify the anti
      hypoxic constituents in the herbs grown in Qinghai-Tibetan plateau of
      Northwestern China. MATERIALS AND METHODS: The anti-hypoxic activities of 20
      selected plateau herbs were examined against two positive controls, Rhodiola
      algida and acetazolamide, using the normobaric hypoxia model of mice. The herb
      with the highest activity was successively extracted with 70% ethanol, petroleum
      ether, chloroform, ethyl acetate and n-butanol. The extract with the highest
      activity was identified by comparing the survival time of mice under normobaric
      hypoxia condition after being subjected to different extracts. The identified
      extract was further tested by simulating high altitudes through an acute
      decompression model and a chronic decompression model for mice. RESULTS: The herb
      found to have the highest anti-hypoxic activity was Saussurea involucrate (Kar.
      et Kir.) Sch.-Bip, and the most effective fraction was in the petroleum ether
      extract. Administration of petroleum ether extract of Saussurea involucrata
      (PESI) to mice at 50mg/kg significantly decreased the mortality of animals under
      acute decompression conditions. Changes in biochemical indicators for
      glycometabolism and energy metabolism, including adenosine triphosphate (ATP)
      content and adenosine triphosphatase (ATPase) activity in brain and cardiac
      muscle, lactic acid (LAC) and lactate dehydrogenase (LDH) in blood and cardiac
      muscles, blood sugar, and glycogen content in liver and skeletal muscle were
      reversed under chronic decompression conditions. CONCLUSIONS: Saussurea
      involucrata (Kar. et Kir.) Sch.-Bip exhibits high anti-hypoxic activity that may
      be effective in preventing acute mountain sickness, and the active constituents
      are mainly in the petroleum ether extract.

PMID- 21893187
TI  - The impact of acute-stressor exposure on splenic innate immunity: a gene
      expression analysis.
AB  - Exposure to intense, acute-stressors modulates immune function. We have
      previously reported, for example, that exposure to a single session of
      inescapable tailshock suppresses acquired and potentiates innate immune responses
      mediated by the spleen. The mechanisms for these changes remain unknown, however,
      they likely involve stress-induced modulation of cytokines. Cytokines operate in
      coordinated networks that include other immunoregulatory factors. Broad-scoped
      analyses are required to gain an understanding of the net-impact of stress on
      these immunoregulatory factors and the immune system. The goal of this study,
      therefore, is to examine the impact of acute-stressor exposure on network-wide
      changes in splenic immunoregulatory factor expression. One hundred and sixty-one
      genes linked to innate immune responses were quantified in the spleen following
      exposure to tailshock using an RT-PCR based gene array. Expression changes in 17
      of the measured genes were confirmed using individual RT-PCR reactions. Further
      assessment of the expression changes using Exploratory Gene Association Networks
      (EGAN) identified important ontologies, processes and pathways that are
      indicative of a broader impact of stress on the immune system. Interestingly,
      EGAN identified several linkages between immunoregulatory factors that may be
      important in explaining previous results concerning the functional consequences
      of stress on splenic immunity. Additional processes, some of which are novel to
      this study, were also uncovered that may be important in directing future studies
      examining the impact of stress on the immune system. In this way, these analyses
      provide a better understanding of how acute stressor exposure modulates splenic
      immunity and may function as predictive tool for future related studies.

PMID- 21893188
TI  - Changes in pro/antioxidant balance in smoking and non-smoking pregnant women with
      intrauterine growth restriction.
AB  - The aim of this study was to investigate the influence of cigarette smoking on
      the pro/antioxidant balance in pregnant women with intrauterine growth
      restriction (IUGR). The studies have shown a 2-fold increase of Cd concentration
      in blood of women with IUGR in labour and a 10-fold increase in smoking pregnant
      women with IUGR. The increase of malondialdehyde concentration in plasma and 8
      hydroxydeoxyguanosine in serum and Cu/Zn superoxide dismutase activity in
      erythrocyte lysate of pregnants with IUGR, reinforced by smoking, was revealed.
      We observed a decrease in the concentration of glutathione in blood and
      glutathione peroxidase activity in plasma and in erythrocyte lysate. A 4-fold
      higher metallothionein concentration in the plasma of women with IUGR in labour
      suggests that metallothionein may be one of the IUGR markers. Metallothionein
      concentration was intensified by smoking up to 7-fold in comparison to the
      controls. The pro/antioxidant balance during pregnancy is significantly affected
      by smoking.

PMID- 21893189
TI  - Occult hepatitis C virus elicits mitochondrial oxidative stress in lymphocytes
      and triggers PI3-kinase-mediated DNA damage response.
AB  - Occult hepatitis C viral infection (OHCI) is a newly reported pathological entity
      associated with increased risk of developing hepatocellular carcinoma and
      lymphoproliferative disorders. Although hepatocytes are the primary sites of
      viral replication, hepatitis C virus is potentially lymphotropic, invading and
      propagating in cells of the immune system. Lymphocytes, the extrahepatic viral
      reservoirs, are differentially implicated in the occult and the active forms of
      the disease. This study aimed to elucidate the implications of mitochondrial
      oxidative stress on the immune pathophysiological mechanisms of OHCI. We herein
      report that OHCI induces mitochondrial oxidative stress, leading to DNA double
      strand breaks and elicitation of a phosphoinositol 3-kinase-mediated cellular
      response in peripheral blood lymphocytes. Compared to controls, OHCI subjects
      showed higher accumulation of pATM, pATR, gammaH2AX, and p-p53, along with active
      recruitment of repair proteins (Mre11, Rad50, and Nbs1) and altered mitochondrial
      DNA content. Increased mitochondrial membrane depolarization and circulating
      nucleosome levels along with chromatid-type aberrations and decreased T-cell
      proliferative index observed in the OHCI group further indicated that this damage
      might lead to Bax-triggered mitochondria-mediated cellular apoptosis. Together
      our results provide the mechanistic underpinnings of mitochondrial dysfunction in
      OHCI, a previously unknown paradigm, for explaining the immune pathogenesis in a
      redox-dependent manner.

PMID- 21893190
TI  - Adverse effects of serotonin depletion in developing zebrafish.
AB  - In this study, p-chlorophenylalanine (pCPA), an inhibitor of tryptophan
      hydroxylase (the rate limiting enzyme of serotonin synthesis), was used to reduce
      serotonin (5HT) levels during early development in zebrafish embryos. One day old
      dechorionated embryos were treated with 25 MUM pCPA for 24h and subsequently
      rescued. Immunohistological studies using a 5HT antibody confirmed that 5HT
      neurons in the brain and spinal cord were depleted of transmitter by 2 days post
      fertilization (dpf). Twenty four hours after pCPA exposure embryos were unable to
      burst swim and were nearly paralyzed. Movement began to improve at 4 dpf, and by
      7 dpf, larvae exhibited swimming activity. Rescued larvae continued to grow in
      rostrocaudal length over 5 days post-rescue, but their length was always 16-21%
      below controls. Surprisingly, both groups displayed the same number of myotomes.
      To examine whether hypertonicity of myotomes in treated embryos played a role in
      their shorter rostrocaudal lengths, 1 dpf embryos were exposed to a combination
      of 25 MUM pCPA and 0.6 mM of the sodium channel blocker ethyl 3-aminobenzoate
      methanesulfonate (MS-222). After a 24 hour exposure, the embryos exhibited the
      same rostrocaudal length as control embryos suggesting that myotome hypertonicity
      plays a major role in the decreased axial length of the treated larvae. In
      addition, pCPA treated 2 dpf embryos exhibited abnormal notochordal morphology
      that persisted throughout recovery. Reverse transcriptase polymerase chain
      reaction (RT-PCR) was performed to determine the relative levels of the serotonin
      1A receptor (5HT(1A)) transcript and the serotonin transporter (SERT) transcript
      in the brain and spinal cord of control and treated embryos. Transcripts were
      present in both brain and spinal cord as early as 1 dpf and reached maximal
      concentrations by 3 dpf. Embryos treated with pCPA demonstrated a decrease in the
      concentration of 5HT(1A) transcript in both brain and spinal cord. While SERT
      transcript levels remained unaffected in brain, they were decreased in spinal
      cord. Five days subsequent to pCPA rescue, 5HT(1A) transcript concentrations
      remained decreased in brain while SERT transcript levels were elevated in both
      regions. These findings suggest that reduction of 5HT during early zebrafish
      development may have an adverse effect on body length, notochordal morphology,
      locomotor behavior, and serotonin message-related expression.

PMID- 21893192
TI  - The third intracellular loop of D1 and D5 dopaminergic receptors dictates their
      subtype-specific PKC-induced sensitization and desensitization in a receptor
      conformation-dependent manner.
AB  - We previously showed that phorbol-12-myristate-13-acetate (PMA) mediates a robust
      PKC-dependent sensitization and desensitization of the highly homologous human Gs
      protein and adenylyl cyclase (AC)-linked D1 (hD1R) and D5 (hD5R) dopaminergic
      receptors, respectively. Here, we demonstrate using forskolin-mediated AC
      stimulation that PMA-mediated hD1R sensitization and hD5R desensitization is not
      associated with changes in AC activity. We next employed a series of chimeric
      hD1R and hD5R to delineate the underlying structural determinants dictating the
      subtype-specific regulation of human D1-like receptors by PMA. We first used
      chimeric receptors in which the whole terminal region (TR) spanning from the
      extracellular face of transmembrane domain 6 to the end of cytoplasmic tail (CT)
      or CT alone were exchanged between hD1R and hD5R. CT and TR swaps lead to
      chimeric hD1R and hD5R retaining PMA-induced sensitization and desensitization of
      wild type parent receptors. In striking contrast, hD1R sensitization and hD5R
      desensitization mediated by PMA are correspondingly switched to PMA-induced
      receptor desensitization and sensitization following the IL3 swap between hD1R
      and hD5R. Cell treatment with the PKC blocker, Go6983, inhibits PMA-induced
      regulation of these chimeric receptors in a similar fashion to wild type
      receptors. Further studies with chimeras constructed by exchanging IL3 and TR
      show that PMA-induced regulation of these chimeras remains fully switched
      relative to their respective wild type parent receptor. Interestingly, results
      obtained with the exchange of IL3 and TR also reveal that the D1-like subtype
      specific regulation by PMA, while fully dictated by IL3, can be modulated in a
      receptor conformation-dependent manner. Overall, our results strongly suggest
      that IL3 is the critical determinant underlying the subtype-specific regulation
      of human D1-like receptor responsiveness by PKC.

PMID- 21893193
TI  - Programmed cell death 6 (PDCD6) inhibits angiogenesis through PI3K/mTOR/p70S6K
      pathway by interacting of VEGFR-2.
AB  - Programmed cell death 6 (PDCD6) was originally found as a pro-apoptotic protein,
      but its molecular mechanism is not well understood. In this study, we have
      attempted to investigate the effects of PDCD6 on the inhibition of angiogenesis
      mediated cell growth as a novel anti-angiogenic protein. Purified recombinant
      human PDCD6 inhibited cell migration in a concentration-time-dependent manner. We
      also found that overexpressed PDCD6 suppressed vascular endothelial growth factor
      (VEGF)-induced proliferation, invasion, and capillary-like structure tube
      formation in vitro. PDCD6 suppressed phosphorylation of signaling regulators
      downstream from PI3K, including Akt, mammalian target of rapamycin (mTOR),
      glycogen synthase kinase-3beta(GSK-3beta), ribosomal protein S6 kinase (p70S6K),
      and also decreased cyclin D1 expression. We found binding PDCD6 to VEGFR-2, a key
      player in the PI3K/mTOR/P70S6K signaling pathway. Taken together, these data
      suggest that PDCD6 plays a significant role in modulating cellular angiogenesis.

PMID- 21893191
TI  - Rac signaling in breast cancer: a tale of GEFs and GAPs.
AB  - Rac GTPases, small G-proteins widely implicated in tumorigenesis and metastasis,
      transduce signals from tyrosine-kinase, G-protein-coupled receptors (GPCRs), and
      integrins, and control a number of essential cellular functions including
      motility, adhesion, and proliferation. Deregulation of Rac signaling in cancer is
      generally a consequence of enhanced upstream inputs from tyrosine-kinase
      receptors, PI3K or Guanine nucleotide Exchange Factors (GEFs), or reduced Rac
      inactivation by GTPase Activating Proteins (GAPs). In breast cancer cells Rac1 is
      a downstream effector of ErbB receptors and mediates migratory responses by
      ErbB1/EGFR ligands such as EGF or TGFalpha and ErbB3 ligands such as heregulins.
      Recent advances in the field led to the identification of the Rac-GEF P-Rex1 as
      an essential mediator of Rac1 responses in breast cancer cells. P-Rex1 is
      activated by the PI3K product PIP3 and Gbetagamma subunits, and integrates
      signals from ErbB receptors and GPCRs. Most notably, P-Rex1 is highly
      overexpressed in human luminal breast tumors, particularly those expressing ErbB2
      and estrogen receptor (ER). The P-Rex1/Rac signaling pathway may represent an
      attractive target for breast cancer therapy.

PMID- 21893194
TI  - Pathophysiologic role of hepatocyte nuclear factor 6.
AB  - Hepatocyte nuclear factor 6 (HNF6) is one of liver-enriched transcription
      factors. HNF6 utilizes the bipartite onecut-homeodomain sequence to localize the
      HNF6 protein to the nuclear compartment and binds to specific DNA sequences of
      numerous target gene promoters. HNF6 regulates an intricate network and mediates
      complex biological processes that are best known in the liver and pancreas. The
      function of HNF6 is correlated to cell proliferation, cell cycle regulation, cell
      differentiation and organogenesis, cell migration and cell-matrix adhesion,
      glucose metabolism, bile homeostasis, inflammation and so on. HNF6 controls the
      transcription of its target genes in different ways. The details of the
      regulatory pathways and their mechanisms are still under investigation. Future
      study will explore HNF6 novel functions associated with apoptosis, oncogenesis,
      and modulation of the inflammatory response. This review highlights recent
      progression pertaining to the pathophysiologic role of HNF6 and summarizes the
      potential mechanisms in preclinical animal models. HNF6-mediated pathways
      represent attractive therapeutic targets for the treatment of the relative
      diseases such as cholestasis.

PMID- 21893196
TI  - Reprint of: Purification of Proteins Using Polyhistidine Affinity Tags.

PMID- 21893195
TI  - A physiologically based model of hepatic ICG clearance: interplay between
      sinusoidal uptake and biliary excretion.
AB  - Although indocyanine green (ICG) has long been used for the assessment of liver
      function, the respective roles of sinusoidal uptake and canalicular excretion in
      determining hepatic ICG clearance remain unclear. Here this issue was addressed
      by incorporating a liver model into a minimal physiological model of ICG
      disposition that accounts of the early distribution phase after bolus injection.
      Arterial ICG concentration-time data from awake dogs under control conditions and
      from the same dogs while anesthetized with 3.5% isoflurane were subjected to
      population analysis. The results suggest that ICG elimination in dogs is uptake
      limited since it depends on hepatocellular uptake capacity and on biliary
      excretion but not on hepatic blood flow. Isoflurane caused a 63% reduction in
      cardiac output and a 33% decrease in the ICG biliary excretion rate constant
      (resulting in a 26% reduction in elimination clearance) while leaving unchanged
      the sinusoidal uptake rate. The terminal slope of the concentration-time curve,
      K, correlated significantly with elimination clearance. The model could be useful
      for assessing the functions of sinusoidal and canalicular ICG transporters.

PMID- 21893197
TI  - Reprint of: Effective high-throughput overproduction of membrane proteins in
      Escherichia coli.
AB  - Structural biology is increasingly reliant on elevated throughput methods for
      protein production. In particular, development of efficient methods of
      heterologous production of membrane proteins is essential. Here, we describe the
      heterologous overproduction of 24 membrane proteins from the human pathogen
      Legionella pneumophila in Escherichia coli. Protein production was performed in
      0.5ml cultures in standard 24-well plates, allowing increased throughput with
      minimal effort. The effect of the location of a histidine purification tag was
      analyzed, and the effect of decreasing the length of the N- and C-terminal
      extensions introduced by the Gateway cloning strategy is presented. We observed
      that the location and length of the purification tag significantly affected
      protein production levels. In addition, an auto-induction protocol for membrane
      protein expression was designed to enhance the overproduction efficiency such
      that, regardless of the construct used, much higher expression was achieved when
      compared with standard induction approaches such as isopropyl-beta-d
      thiogalactopyranoside (IPTG). All 24 targets were produced at levels exceeding
      2mg/l, with 18 targets producing at levels of 5mg/l or higher. In summary, we
      have designed a fast and efficient process for the production of medically
      relevant membrane proteins with a minimum number of screening parameters.

PMID- 21893199
TI  - Reprint of: Expression and purification of ataxin-1 protein.
AB  - Ataxin-1 is part of a larger family of polyglutamine-containing proteins that is
      linked to nine distinct neurodegenerative disorders. There are no known effective
      therapies for any of these expanded polyglutamine tract disorders. One possible
      reason for this is the lack of sufficient amounts of pure polyglutamine
      containing proteins suitable for biochemical and conformational studies. Here, we
      show that we were able to successfully purify a non-pathological, wild-type human
      ataxin-1 protein containing a 30-glutamine repeat sequence. This ataxin-1 protein
      was expressed in Escherichia coli as a fusion protein with a GST tag at the N
      terminus and a double (His)(6) tag at the C-terminus. The devised dual affinity
      tag strategy allowed successful purification of the full-length ataxin-1 fusion
      protein to 90% homogeneity as confirmed by Western blot analysis using the two
      monoclonal ataxin-1 antibodies developed in our laboratory. In addition, the GST
      tag was successfully removed from the purified ataxin-1 fusion protein by
      treatment with Tobacco etch virus (TEV) protease. Since polyglutamine-containing
      proteins tend to aggregate, solvents/buffers that minimize aggregation have been
      used in the purification process. This dual affinity purification protocol could
      serve as a useful basis for purifying aggregation-prone proteins that are
      involved in other neurodegenerative diseases.

PMID- 21893200
TI  - Reprint of: Immobilized-Metal Affinity Chromatography (IMAC): A Review.
AB  - This article reviews the development of immobilized-metal affinity chromatography
      (IMAC) and describes its most important applications. We provide an overview on
      the use of IMAC in protein fractionation and proteomics, in protein
      immobilization and detection, and on some special applications such as
      purification of immunoglobulins and the Chelex method. The most relevant
      application- purification of histidine-tagged recombinant proteins-will be
      reviewed in greater detail with focus of state-of-the-art materials, methods, and
      protocols, and the limitations of IMAC and recent advances to improve the
      technology and the methods will be described.

PMID- 21893201
TI  - Reprint of: Making the most of affinity tags.
AB  - Proteins do not naturally lend themselves to high-throughput analysis because of
      their diverse physiochemical properties. Consequently, affinity tags have become
      indispensable tools for structural and functional proteomics initiatives.
      Although originally developed to facilitate the detection and purification of
      recombinant proteins, in recent years it has become clear that affinity tags can
      have a positive impact on the yield, solubility and even the folding of their
      fusion partners. However, no single affinity tag is optimal with respect to all
      of these parameters; each has its strengths and weaknesses. Therefore,
      combinatorial tagging might be the only way to harness the full potential of
      affinity tags in a high-throughput setting.

PMID- 21893202
TI  - Reprint of: Influence of the protein oligomericity on final yield after affinity
      tag removal in purification of recombinant proteins.
AB  - The new aspect concerning the applicability of histidine and other affinity tags
      for the purification of oligomeric proteins, with particular emphasis on cleavage
      efficiency and final yield, is presented in this study. The final yield depends
      on both the cleavage efficiency and the degree of oligomerization of the protein.
      Cleavage procedures that are good enough for monomeric proteins can be
      problematic for oligomeric proteins. Random distribution of uncleaved or
      partially cleaved affinity tags among oligomers is the main cause of reduced
      yields. A trimeric protein, tumour necrosis factor alpha (TNF-alpha), bearing
      different histidine tags, was used as a model protein to explore and confirm this
      theoretical concept. Analysis of mixed TNF trimers, prepared from tag-free TNF
      doped with various amounts of histidine-tagged TNF, revealed an increased
      retention of the trimeric protein on immobilized metal-ion affinity
      chromatography (IMAC) columns. When 20% of histidine-tagged TNF was added, more
      than 50% of the protein was retained on the IMAC column. Thus, the applicability
      of histidine- and other affinity tags for purifying oligomeric proteins is
      significantly prejudiced in the case of higher oligomers. Various histidine-tags
      were fused to the N-terminus of full-length TNF-alpha and to the truncated form
      (dN6) of TNF-alpha. Two-step IMAC separation was used for purification. In the
      first step, IMAC-1, over 95% purity of histidine-tagged protein was achieved in
      all cases. Endo- and exoproteolytic removal of histidine tags with enterokinase
      (EKmax) and aminodipeptidase (DAPase) was studied and the major parameters
      affecting cleavage efficiency, microheterogeneity and final yield are critically
      discussed. IMAC-2 was used as the second and final step for removing the cleavage
      enzyme, cleaved tags, unprocessed protein and some other impurities. Selection of
      the optimal cleavage enzyme depends on the amino acid composition of the N
      terminus and the intended use of the purified protein. The main conclusion is
      that special caution should be taken when introducing affinity tags to oligomeric
      proteins, with the final goal to produce pure, tag-free protein with acceptable
      yields. Given the same enzyme cleavage efficiency one can expect progressively
      reduced final protein yields with increasing degree of oligomerization. This
      should be considered as a general rule.

PMID- 21893203
TI  - Reprint of: Comparison of affinity tags for protein purification.
AB  - Affinity tags are highly efficient tools for purifying proteins from crude
      extracts. To facilitate the selection of affinity tags for purification projects,
      we have compared the efficiency of eight elutable affinity tags to purify
      proteins from Escherichia coli, yeast, Drosophila, and HeLa extracts. Our results
      show that the HIS, CBP, CYD (covalent yet dissociable NorpD peptide), Strep II,
      FLAG, HPC (heavy chain of protein C) peptide tags, and the GST and MBP protein
      fusion tag systems differ substantially in purity, yield, and cost. We find that
      the HIS tag provides good yields of tagged protein from inexpensive, high
      capacity resins but with only moderate purity from E. coli extracts and
      relatively poor purification from yeast, Drosophila, and HeLa extracts. The CBP
      tag produced moderate purity protein from E. coli, yeast, and Drosophila
      extracts, but better purity from HeLa extracts. Epitope-based tags such as FLAG
      and HPC produced the highest purity protein for all extracts but require
      expensive, low capacity resin. Our results suggest that the Strep II tag may
      provide an acceptable compromise of excellent purification with good yields at a
      moderate cost.

PMID- 21893204
TI  - Identification of an artificial peptide motif that binds and stabilizes reduced
      human DJ-1.
AB  - Although the precise biochemical function of DJ-1 remains unclear, it has been
      found to exert cytoprotective activity against oxidative stress. Cys106 is
      central to this function since it has a distinctly low pK(a) rendering it
      extremely susceptible for oxidation. This characteristic, however, also poses a
      severe hindrance to obtain reduced DJ-1 for in vitro investigation. We have
      developed an approach to produce recombinant human DJ-1 in its reduced form as a
      bona fide basis for exploring the redox capacities of the protein. We solved the
      crystal structure of this DJ-1 at 1.56A resolution, allowing us to capture Cys106
      in the reduced state for the first time. The dimeric structure reveals one
      molecule of DJ-1 in its reduced state while the other exhibits the
      characteristics of a mono-oxygenated cysteine. Comparison with previous
      structures indicates the absence of redox dependent global conformational changes
      in DJ-1. The capture of reduced Cys106 is facilitated by stabilization within the
      putative active site achieved through a glutamate side chain. This side chain is
      provided by a crystallographic neighbor as part of a 'Leu-Glu' motif, which was
      added to the C-terminus of DJ-1. In the structure this motif binds DJ-1 in close
      proximity to Cys106 through extended hydrophilic and hydrophobic interactions
      depicting a distinct binding pocket, which can serve as a basis for compound
      development targeting DJ-1.

PMID- 21893205
TI  - White matter atlas generation using HARDI based automated parcellation.
AB  - Most diffusion imaging studies have used subject registration to an atlas space
      for enhanced quantification of anatomy. However, standard diffusion tensor
      atlases lack information in regions of fiber crossing and are based on adult
      anatomy. The degree of error associated with applying these atlases to studies of
      children for example has not yet been estimated but may lead to suboptimal
      results. This paper describes a novel technique for generating population
      specific high angular resolution diffusion imaging (HARDI)-based atlases
      consisting of labeled regions of homogenous white matter. Our approach uses a
      fiber orientation distribution (FOD) diffusion model and a data driven clustering
      algorithm. White matter regional labeling is achieved by our automated data
      driven clustering algorithm that has the potential to delineate white matter
      regions based on fiber complexity and orientation. The advantage of such an atlas
      is that it is study specific and more comprehensive in describing regions of
      white matter homogeneity as compared to standard anatomical atlases. We have
      applied this state of the art technique to a dataset consisting of adolescent and
      preadolescent children, creating one of the first examples of a HARDI-based
      atlas, thereby establishing the feasibility of the atlas creation framework. The
      white matter regions generated by our automated clustering algorithm have lower
      FOD variance than when compared to the regions created from a standard anatomical
      atlas.

PMID- 21893206
TI  - Grouping of MEG gamma oscillations by EEG sleep spindles.
AB  - Studies have revealed an association between EEG sleep spindles and processing of
      memories during sleep. Here we investigated whether there is a temporal relation
      between sleep spindles and MEG oscillatory activity in the gamma frequency band
      (>30 Hz) which is considered to reflect local cortical processing of memory
      representations. MEG and simultaneous EEG (at Cz) were obtained in subjects
      during sleep together with standard polysomnography. As expected EEG spindles
      were correlated with power increases in MEG spindle (12.5-15.5 Hz) power mainly
      over prefrontal and occipital cortical areas. During EEG spindles we revealed
      both transient significant increases and decreases in MEG power, with decreases
      occurring significantly more often than increases. The modulations in gamma power
      occurred mainly at sites of increased MEG spindle power, and more often during
      peaks than troughs within the EEG spindle cycle. Cross-frequency coherence
      analyses confirmed a strong phase-coupling of gamma band activity with the
      spindle rhythm. The findings are consistent with the idea that spindles provide a
      fine-tuned temporal frame for integrated cortical memory processing during sleep.

PMID- 21893207
TI  - Direct evidence of intra- and interhemispheric corticomotor network degeneration
      in amyotrophic lateral sclerosis: an automated MRI structural connectivity study.
AB  - Although the pathogenesis of amyotrophic lateral sclerosis (ALS) is uncertain,
      there is mounting neuroimaging evidence to suggest a mechanism involving the
      degeneration of multiple white matter (WM) motor and extramotor neural networks.
      This insight has been achieved, in part, by using MRI Diffusion Tensor Imaging
      (DTI) and the voxelwise analysis of anisotropy indices, along with DTI
      tractography to determine which specific motor pathways are involved with ALS
      pathology. Automated MRI structural connectivity analyses, which probe WM
      connections linking various functionally discrete cortical regions, have the
      potential to provide novel information about degenerative processes within
      multiple white matter (WM) pathways. Our hypothesis is that measures of altered
      intra- and interhemispheric structural connectivity of the primary motor and
      somatosensory cortex will provide an improved assessment of corticomotor
      involvement in ALS. To test this hypothesis, we acquired High Angular Resolution
      Diffusion Imaging (HARDI) scans along with high resolution structural images
      (sMRI) on 15 patients with clinical evidence of upper and lower motor neuron
      involvement, and 20 matched control participants. Whole brain probabilistic
      tractography was applied to define specific WM pathways connecting discrete
      corticomotor targets generated from anatomical parcellation of sMRI of the brain.
      The integrity of these connections was interrogated by comparing the mean
      fractional anisotropy (FA) derived for each WM pathway. To assist in the
      interpretation of results, we measured the reproducibility of the FA summary
      measures over time (6months) in control participants. We also incorporated into
      our analysis pipeline the evaluation and replacement of outlier voxels due to
      head motion and physiological noise. When assessing corticomotor connectivity, we
      found a significant reduction in mean FA within a number of intra- and
      interhemispheric motor pathways in ALS patients. The abnormal intrahemispheric
      pathways include the corticospinal tracts involving the left and right precentral
      gyri (lh.preCG, rh.preCG) and brainstem (bs); right postcentral gyrus (rh.postCG)
      and bs; lh.preCG and left posterior cingulate gyrus (lh.PCG); rh.preCG and right
      posterior cingulate gyrus (rh.PCG); and the rh.preCG and right paracentral gyrus
      (rh.paraCG). The abnormal interhemispheric pathways included the lh.preCG and
      rh.preCG; lh.preCG and rh.paraCG; lh.preCG and right superior frontal gyrus
      (rh.supFG); lh.preCG and rh.postCG; rh.preCG and left paracentral gyrus
      (lh.paraCG); rh.preCG and left superior frontal gyrus (lh.supFG); and the
      rh.preCG and left caudal middle frontal gyrus (lh.caudMF). The reproducibility of
      the measurement of these pathways was high (variation less than 5%). Maps of the
      outlier rejection voxels, revealed clusters within the corpus callosum and
      corticospinal projections. This finding highlights the importance of correcting
      for motion artefacts and physiological noise when studying clinical populations.
      Our novel findings, many of which are consistent with known pathology, show
      extensive involvement and degeneration of multiple corticomotor pathways in
      patients with upper and lower motor neuron signs and provide support for the use
      of automated structural connectivity techniques for studying neurodegenerative
      disease processes.

PMID- 21893209
TI  - Iron and copper in fetal development.
AB  - Copper and iron are both essential micronutrients. Because they can both accept
      and donate electrons, they are central to many energy dependent chemical
      reactions. For example, copper is a critical part of ferroxidase enzymes
      ceruloplasmin, hephaestin and zyklopen, as well as enzymes such as dopamine-beta
      monoxygenase, while iron is part of the catalytic site of many cytochromes and
      enzymes involved in fatty acid desaturation. Unsurprisingly, therefore, copper
      and iron deficiency, especially during pregnancy, when cell proliferation and
      differentiation are very active, sub-optimal nutrient status can lead to serious
      consequences. These problems can persist into adulthood, with an increased risk
      of mental problems such as schizophrenia and, in animal models at least,
      hypertension and obesity. In this review, we consider what these problems are and
      how they may arise. We examine the role of copper and iron deficiencies
      separately during fetal development, in terms of birth outcome and then how
      problems with status in utero can have long term sequelae for the offspring. We
      examine several possible mechanisms of action, both direct and indirect. Direct
      causes include, for example, reduced enzyme activity, while indirect ones may
      result from changes in cytokine activity, reductions in cell number or increased
      apoptosis, to name but a few. We examine a very important area of nutrition
      interactions between the micronutrients and conclude that, while we have made
      significant advances in understanding the relationship between micronutrient
      status and pregnancy outcome, there is still much to be learned.

PMID- 21893208
TI  - Susceptibility induced gray-white matter MRI contrast in the human brain.
AB  - MR phase images have shown significantly improved contrast between cortical gray
      and white matter regions compared to magnitude images obtained with gradient echo
      sequences. A variety of underlying biophysical mechanisms (including iron, blood,
      myelin content, macromolecular chemical exchange, and fiber orientation) have
      been suggested to account for this observation but assessing the individual
      contribution of these factors is limited in vivo. For a closer investigation of
      iron and myelin induced susceptibility changes, postmortem MRI of six human
      corpses (age range at death: 56-80 years) was acquired in situ. Following
      autopsy, the iron concentrations in the frontal and occipital cortex as well as
      in white matter regions were chemically determined. The magnetization transfer
      ratio (MTR) was used as an indirect measure for myelin content. Susceptibility
      effects were assessed separately by determining R2* relaxation rates and
      quantitative phase shifts. Contributions of myelin and iron to local variations
      of the susceptibility were assessed by univariate and multivariate linear
      regression analysis. Mean iron concentration was lower in the frontal cortex than
      in frontal white matter (26 +/- 6 vs. 45 +/- 6 mg/kg wet tissue) while an inverse
      relation was found in the occipital lobe (cortical gray matter: 41 +/- 10 vs.
      white matter: 34 +/- 10mg/kg wet tissue). Multiple regression analysis revealed
      iron and MTR as independent predictors of the effective transverse relaxation
      rate R2 but solely MTR was identified as source of MR phase contrast. R2 was
      correlated with iron concentrations in cortical gray matter only (r=0.42,
      p<0.05). In conclusion, MR phase contrast between cortical gray and white matter
      can be mainly attributed to variations in myelin content, but not to iron
      concentration. Both, myelin and iron impact the effective transverse relaxation
      rate R2 significantly. Magnitude contrast is limited because it only reflects the
      extent but not the direction of the susceptibility shift.

PMID- 21893210
TI  - Reversible metabolic depression in lamprey hepatocytes during prespawning
      migration: dynamics of mitochondrial membrane potential.
AB  - The lamprey (Lampetra fluviatilis L.) is an extant representative of the ancient
      vertebrate group of Agnathans. During the prespawning migration (the river period
      of life from autumn until spring) lamprey hepatocytes exhibit widely different
      energy states: a high-energy state in autumn and spring, corresponding to a
      normal physiological standard, and a low-energy state in winter, which is
      provoked by prolonged starvation and profound metabolic arrest. In spring the
      restoration of energy status (return to an active state) is associated with
      hormonally induced lipolysis of the lipid droplets stored in the cells. Lamprey
      hepatocytes demonstrate an aerobic metabolism based on oxidation of free fatty
      acids. The dynamics of mitochondrial membrane potential (MMP) were measured
      throughout the prespawning migration. Pharmacological inhibition of the electron
      transport chain decreased the MMP and caused extensive depletion of cellular ATP
      without loss of cell viability. The potential molecular mechanisms responsible
      for winter metabolic depression in lamprey hepatocytes are discussed.

PMID- 21893211
TI  - Molecular cloning, expression analysis of insulin-like growth factor I (IGF-I)
      gene and IGF-I serum concentration in female and male Tongue sole (Cynoglossus
      semilaevis).
AB  - Insulin-like growth factor I (IGF-I) is a polypeptide hormone that regulates
      growth during all stages of development in vertebrates. To examine the mechanisms
      of the sexual growth dimorphism in the Tongue sole (Cynoglossus semilaevis),
      molecular cloning, expression analysis of IGF-I gene and IGF-I serum
      concentration analysis were performed. As a result, the IGF-I cDNA sequence is
      911 bp, which contains an open reading frame (ORF) of 564 bp encoding a protein
      of 187 amino acids. The sex-specific tissue expression was analyzed by using 14
      tissues from females, normal males and extra-large male adults. The IGF-I mRNA
      was predominantly expressed in liver, and the IGF-I expression levels in females
      and extra-large males were 1.9 and 10.2 times as much as those in normal males,
      respectively. Sex differences in IGF-I mRNA expressions at early life stages were
      also examined by using a full-sib family of C. semilaevis, and the IGF-I mRNA was
      detected at all of the 27 sampling points from 10 to 410 days old. An increase in
      IGF-I mRNA was detected after 190 day old fish. The significantly higher levels
      of IGF-I mRNA in females were observed after 190 days old in comparison with
      males (P<0.01). The IGF-I concentrations in serum of mature individuals were
      detected by ELISA. The IGF-I level in the serum of females was approximately two
      times as much as that of males. Consequently, IGF-I may play an important role in
      the endocrine regulation of the sexually dimorphic growth of C. semilaevis.

PMID- 21893212
TI  - Complexes of mismatched and complementary DNA with minor groove binders.
      Structures at nucleotide resolution via an improved hydroxyl radical cleavage
      methodology.
AB  - Tumor cell lines can replicate faster than normal cells and many also have
      defective DNA repair pathways. This has lead to the investigation of the
      inhibition of DNA repair proteins as a means of therapeutic intervention. An
      alternative approach is to hide or mask damaged DNA from the repair systems. We
      have developed a protocol to investigate the structures of the complexes of
      damaged DNA with drug like molecules. Nucleotide resolution structural
      information can be obtained using an improved hydroxyl radical cleavage protocol.
      The use of a dT(n) tail increases the length of the smallest fragments of
      interest and allows efficient co-precipitation of the fragments with poly(A). The
      use of a fluorescent label, on the 5' end of the dT(n) tail, in conjunction with
      modified cleavage reaction conditions, avoids the lifetime and other problems
      with (32)P labeling. The structures of duplex DNAs containing AC and CC
      mismatches in the presence and absence of minor groove binders have been
      investigated as have those of the fully complementary DNA. The results indicate
      that the structural perturbations of the mismatches are localized, are sequence
      dependent and that the presence of a mismatch can alter the binding of drug like
      molecules.

PMID- 21893213
TI  - The current status of opisthorchiasis and clonorchiasis in the Mekong Basin.
AB  - This review highlights the current status and control of liver fluke infections
      in the Mekong Basin countries where Opisthorchis and Clonorchis are highly
      endemic. Updated data on prevalence and distribution have been summarized from
      presentations in the "96 Years of Opisthorchiasis. International Congress of
      Liver Flukes". It is disturbing that despite treatment and control programs have
      been in place for decades, all countries of the Lower Mekong Basin are still
      highly endemic with O. viverrini and/or C. sinensis as well as alarmingly high
      levels of CCA incidence. A common pattern that is emerging in each country is the
      difference in transmission of O. viverrini between lowlands which have high
      prevalence versus highlands which have low prevalence. This seems to be
      associated with wetlands, flooding patterns and human movement and settlement. A
      more concerted effort from all community, educational, public health and
      government sectors is necessary to successfully combat this fatal liver disease
      of the poor.

PMID- 21893214
TI  - Retraction notice to "Pigment epithelium-derived factor inhibits vascular
      endothelial growth factor-and interleukin-1beta-induced vascular permeability and
      angiogenesis in retinal endothelial cells" Vascular Pharmacology 52 (2010) 84-94.

PMID- 21893215
TI  - Block urn design - a new randomization algorithm for sequential trials with two
      or more treatments and balanced or unbalanced allocation.
AB  - Permuted block design is the most popular randomization method used in clinical
      trials, especially for trials with more than two treatments and unbalanced
      allocation, because of its consistent imbalance control and simplicity in
      implementation. However, the risk of selection biases caused by high proportion
      of deterministic assignments is a cause of concern. Efron's biased coin design
      and Wei's urn design provide better allocation randomness without deterministic
      assignments, but they do not consistently control treatment imbalances.
      Alternative randomization designs with improved performances have been proposed
      over the past few decades, including Soares and Wu's big stick design, which has
      high allocation randomness, but is limited to two-treatment balanced allocation
      scenarios only, and Berger's maximal procedure design which has a high allocation
      randomness and a potential for more general trial scenarios, but lacks the
      explicit function for the conditional allocation probability and is more complex
      to implement than most other designs. The block urn design proposed in this paper
      combines the advantages of existing randomization designs while overcoming their
      limitations. Statistical properties of the new algorithm are assessed and
      compared to currently available designs via analytical and computer simulation
      approaches. The results suggest that the block urn design simultaneously provides
      consistent imbalance control and high allocation randomness. It can be easily
      implemented for sequential clinical trials with two or more treatments and
      balanced or unbalanced allocation.

PMID- 21893216
TI  - Lactobacillus plantarum strain YU from fermented foods activates Th1 and
      protective immune responses.
AB  - Lactic acid bacteria (LAB) are known to have effects on immune function. From 203
      strains of LAB isolated from fermented foods, we selected a beneficial strain,
      Lactobacillus plantarum strain YU (LpYU), which has high interleukin (IL)-12
      inducing activity in mouse peritoneal macrophages. This activity of LpYU was
      partially mediated by Toll-like receptor (TLR) 2, but not TLR4 or TLR9. Oral
      administration of LpYU to ovalbumin (OVA)-immunized mice caused suppression of
      serum OVA-specific immunoglobulin E (IgE) levels, enhancing interferon (IFN)
      gamma production from spleen cells in response to OVA. Furthermore, LpYU enhanced
      natural killer cell activity in spleen cells and the production of IgA from
      Peyer's patch cells. Because activation of Th1 immune responses and IgA
      production induce antiviral effects, we evaluated the inhibitory effects of LpYU
      against the influenza A virus (A/NWS/33, H1N1) (IFV). Oral administration of LpYU
      suppressed viral proliferation in the lungs and in bronchoalveolar lavage fluids
      (BALFs). Both levels of IFV-specific secretory IgA in BALF and feces and titers
      of IFV-specific neutralizing antibody in BALFs and sera were increased. These
      results indicate that LpYU has a protective effect against IFV replication. We
      conclude that this strain has a beneficial effect in activating Th1 immune
      responses and preventing viral infection.

PMID- 21893218
TI  - The mitochondrial proteome of the model legume Medicago truncatula.
AB  - Legumes carry out special biochemical functions, e.g. the fixation of molecular
      nitrogen based on a symbiosis with proteobacteria. At the cellular level, this
      symbiosis has to be implemented into the energy metabolism of the host cell. To
      provide a basis for future analyses, we have characterized the protein complement
      of mitochondria of the model legume Medicago truncatula using two-dimensional
      isoelectric focussing (IEF) and blue-native (BN)-SDS-PAGE. While the IEF
      reference map resulted mainly in resolution of those proteins associated with the
      mitochondrial matrix, the BN proteomic map allowed separation of protein subunits
      from the respiratory chain protein complexes, which are located in the
      organelle's inner membrane. The M. truncatula mitochondrial BN reference map
      revealed some striking similarities to the one from Arabidopsis thaliana but at
      the same time exhibited also some special features: complex II is of increased
      abundance and additionally represented by a low molecular mass form not reported
      for Arabidopsis. Furthermore three highly abundant forms of prohibitin complexes
      are present in the mitochondrial proteome of M. truncatula. Special features with
      respect to mitochondrial protein complexes might reflect adaptations of legumes
      to elevated cellular energy requirements enabling them to develop symbiotic
      interactions with rhizobial bacteria.

PMID- 21893217
TI  - Genetic variation of alphaENaC influences lung diffusion during exercise in
      humans.
AB  - Exercise, decompensated heart failure, and exposure to high altitude have been
      shown to cause symptoms of pulmonary edema in some, but not all, subjects,
      suggesting a genetic component to this response. Epithelial Na(+) Channels (ENaC)
      regulate Na(+) and fluid reabsorption in the alveolar airspace in the lung. An
      increase in number and/or activity of ENaC has been shown to increase lung fluid
      clearance. Previous work has demonstrated common functional genetic variants of
      the alpha-subunit of ENaC, including an A->T substitution at amino acid 663
      (alphaA663T). We sought to determine the influence of the T663 variant of
      alphaENaC on lung diffusion at rest and at peak exercise in healthy humans.
      Thirty healthy subjects were recruited for study and grouped according to their
      SCNN1A genotype [n=17 vs. 13, age=25+/-7 years vs. 30+/-10 years, BMI=23+/-4
      kg/m(2) vs. 25+/-4 kg/m(2), V(O2 peak) = 95+/-30%pred. vs. 100+/-31%pred., mean+/
      SD, for AA (homozygous for alphaA663) vs. AT/TT groups (at least one alphaT663),
      respectively]. Measures of the diffusing capacity of the lungs for carbon
      monoxide (DL(CO)), the diffusing capacity of the lungs for nitric oxide (DL(NO)),
      alveolar volume (V(A)), and alveolar-capillary membrane conductance (D(M)) were
      taken at rest and at peak exercise. Subjects expressing the AA polymorphism of
      ENaC showed a significantly greater percent increase in DL(CO) and DL(NO), and a
      significantly greater decrease in systemic vascular resistance from rest to peak
      exercise than those with the AT/TT variant (DL(CO)=51+/-12% vs. 36+/-17%,
      DL(NO)=51+/-24% vs. 32+/-25%, SVR=-67+/-3 vs. -50+/-8%, p<0.05). The AA ENaC
      group also tended to have a greater percent increase in DL(CO)/VA from rest to
      peak exercise, although this did not reach statistical significance (49+/-26% vs.
      33+/-26%, p=0.08). These results demonstrate that genetic variation of the alpha
      subunit of ENaC at amino acid 663 influences lung diffusion at peak exercise in
      healthy humans, suggesting differences in alveolar Na(+) and, therefore, fluid
      handling. These findings could be important in determining who may be susceptible
      to pulmonary edema in response to various clinical or environmental conditions.

PMID- 21893219
TI  - Characterization of JBURE-IIb isoform of Canavalia ensiformis (L.) DC urease.
AB  - Ureases, nickel-dependent enzymes that catalyze the hydrolysis of urea into
      ammonia and bicarbonate, are widespread in plants, bacteria, and fungi.
      Previously, we cloned a cDNA encoding a Canavalia ensiformis urease isoform named
      JBURE-II, corresponding to a putative smaller urease protein (78kDa) when
      compared to other plant ureases. Aiming to produce the recombinant protein, we
      obtained jbure-IIb, with different 3' and 5' ends, encoding a 90kDa urease. Three
      peptides unique to the JBURE-II/-IIb protein were detected by mass spectrometry
      in seed extracts, indicating that jbure-II/-IIb is a functional gene. Comparative
      modeling indicates that JBURE-IIb urease has an overall shape almost identical to
      C. ensiformis major urease JBURE-I with all residues critical for urease
      activity. The cDNA was cloned into the pET101 vector and the recombinant protein
      was produced in Escherichia coli. The JBURE-IIb protein, although enzymatically
      inactive presumably due to the absence of Ni atoms in its active site, impaired
      the growth of a phytopathogenic fungus and showed entomotoxic properties,
      inhibiting diuresis of Rhodnius prolixus isolated Malpighian tubules, in
      concentrations similar to those reported for JBURE-I and canatoxin. The
      antifungal and entomotoxic properties of the recombinant JBURE-IIb apourease are
      consistent with a protective role of ureases in plants.

PMID- 21893220
TI  - A girl with an atypical form of ataxia telangiectasia and an additional de novo
      3.14 Mb microduplication in region 19q12.
AB  - A 9-year-old girl born to healthy parents showed manifestations suggestive of
      ataxia telangiectasia (AT), such as short stature, sudden short bouts of
      horizontal and rotary nystagmus, a weak and dysarthric voice, rolling gait,
      unstable posture, and atactic movements. She did not show several cardinal
      features typical of AT such as frequent, severe infections of the respiratory
      tract. In contrast, she showed symptoms not generally related to AT, including
      microcephaly, profound motor and mental retardation, small hands and feet,
      severely and progressively reduced muscle tone with slackly protruding abdomen
      and undue drooling, excess fat on her upper arms, and severe oligoarthritis. A
      cranial MRI showed no cerebellar hypoplasia and other abnormalities. In
      peripheral blood samples she carried a de novo duplication of 3.14 Mb in
      chromosomal region 19q12 containing six annotated genes, UQCRFS1, VSTM2B, POP4,
      PLEKHF1, CCNE1, and ZNF536, and a de novo mosaic inversion 14q11q32 (96% of
      metaphases). In a saliva-derived DNA sample only the duplication in 19q12 was
      detected, suggesting that the rearrangements in blood lymphocytes were acquired.
      These findings reinforced the suspicion that she had AT. AT was confirmed by
      strongly elevated serum AFP levels, cellular radiosensitivity and two inherited
      mutations in the ATM gene (c.510_511delGT; paternal origin and c.2922
      50_2940del69; maternal origin). This case suggest that a defective ATM-dependent
      DNA damage response may entail additional stochastic genomic rearrangements.
      Screening for genomic rearrangements appears indicated in patients suspected of
      defective DNA damage responses.

PMID- 21893221
TI  - A Wolff in sheep's clothing: trabecular bone adaptation in response to changes in
      joint loading orientation.
AB  - This study tests Wolff's law of trabecular bone adaptation by examining if
      induced changes in joint loading orientation cause corresponding adjustments in
      trabecular orientation. Two groups of sheep were exercised at a trot, 15 min/day
      for 34 days on an inclined (7 degrees ) or level (0 degrees ) treadmills. Incline
      trotting caused the sheep to extend their tarsal joints by 3-4.5 degrees  during
      peak loading (P<0.01) but has no effect on carpal joint angle (P=0.984).
      Additionally, tarsal joint angle in the incline group sheep were maintained more
      extended throughout the day using elevated platform shoes on their forelimbs. A
      third "sedentary group" group did not run but wore platform shoes throughout the
      day. As predicted by Wolff's law, trabecular orientation in the distal tibia
      (tarsal joint) were more obtuse by 2.7 to 4.3 degrees  in the incline group
      compared to the level group; trabecular orientation was not significantly
      different in the sedentary and level groups. In addition, trabecular orientations
      in the distal radius (carpal joint) of the sedentary, level and incline groups
      did not differ between groups, and were aligned almost parallel to the radius
      long axis, corresponding to the almost straight carpal joint angle at peak
      loading. Measurements of other trabecular bone parameters revealed additional
      responses to loading, including significantly higher bone volume fraction
      (BV/TV), Trabecular number (Tb.N) and trabecular thickness (Tb.Th), lower
      trabecular spacing (Tb.Sp), and less rod-shaped trabeculae (higher structure
      model index, SMI) in the exercised than sedentary sheep. Overall, these results
      demonstrate that trabecular bone dynamically adjusts and realigns itself in very
      precise relation to changes in peak loading direction, indicating that Wolff's
      law is not only accurate but also highly sensitive.

PMID- 21893222
TI  - Zinc deficiency decreases osteoblasts and osteoclasts associated with the reduced
      expression of Runx2 and RANK.
AB  - The effects of Zinc(Zn)-deficiency on the function and differentiation of
      osteoblasts and osteoclasts were investigated in vivo using rats, which were fed
      a Zn-adequate (control) or Zn-free diet (ZD) or pair-fed a Zn-adequate diet (PF)
      for 3 weeks. Levels of Zn, insulin, insulin-like growth factor I (IGF-I), and
      osteoclacin in serum and the activities and numbers of osteoblasts and
      osteoclasts in bone decreased in ZD rats compared with the control and PF rats.
      The frequency analyses showed that the precursors of osteoblasts and osteoclasts
      decreased in bone marrow of ZD, but not PF, rats. The expression of receptor for
      activation of NF-kappaB (RANK) decreased with the Zn-deficiency, although RANK
      ligand, osteoprotegerin, macrophage colony-stimulating factor, and c-fms levels
      were unaltered. The protein level of a transcription factor MITF, but not PU.1,
      decreased. The expression of Runx2 decreased associated with the decrease in beta
      catenin protein and the suppression of glycogen synthase kinase 3beta (GSK3beta)
      inhibition and Akt activation. The gene expression of the insulin receptor, IGF-I
      and the IGF-I receptor was decreased with a reduced level of transcription factor
      SP-1. These results suggested that a deficiency of Zn decreased
      osteoclastogenesis associated with the reduced expression of RANK through a
      decrease in MITF protein, and osteoblastogenesis associated with the reduced
      expression of Runx2 through the inhibition of Wnt/beta-catenin signaling via the
      suppression of GSK3beta inhibition and Akt activation preceded by the reduced
      level of SP-1 protein.

PMID- 21893223
TI  - Investigating the mechanism for maintaining eucalcemia despite immobility and
      anuria in the hibernating American black bear (Ursus americanus).
AB  - Ursine hibernation uniquely combines prolonged skeletal unloading, anuria,
      pregnancy, lactation, protein recycling, and lipolysis. This study presents a
      radiographic and biochemical picture of bone metabolism in free-ranging, female
      American black bears (Ursus americanus) that were active (spring bears and autumn
      bears) or hibernating (hibernating bears). Hibernating bears included lactating
      and non-lactating individuals. We measured serum calcium, albumin, inorganic
      phosphate, creatinine, bone specific alkaline phosphatase (BSALP), CTX,
      parathyroid hormone, insulin-like growth factor-I (IGF-l), leptin, 25
      hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and sclerostin
      from 35 to 50 tranquilized hibernating bears and 14 to 35 tranquilized spring
      bears. We compared metacarpal cortical indices (MCI), measured by digital X-ray
      radiogrammetry, from 60 hunter-killed autumn bears and 79 tranquilized,
      hibernating bears. MCI was greater in autumn than winter in younger bears, but
      showed no seasonal difference in older bears. During hibernation eucalcemia was
      maintained, BSALP was suppressed, and CTX was in the range expected for anuria.
      During hibernation 1,25(OH)(2)D was produced despite anuria. 1,25(OH)(2)D and IGF
      I were less in hibernating than spring bears. In a quarter of hibernating bears,
      sclerostin was elevated. Leptin was greater in hibernating than spring bears. In
      hibernating bears, leptin correlated positively with BSALP in non-lactating bears
      and with CTX in lactating bears. Taken together the biochemical and radiographic
      findings indicate that during hibernation, bone turnover was persistent,
      balanced, and suppressed; bone resorption was lower than expected for an unloaded
      skeleton; and there was no unloading-induced bone loss. The skeleton appears to
      perceive that it was loaded when it was actually unloaded during hibernation.
      However, at the level of sclerostin, the skeleton recognized that it was
      unloaded. During hibernation leptin appeared anabolic in non-lactating bears and
      catabolic in lactating bears. We hypothesize that ursine hibernation may
      represent a natural model in which suppression of the sympathetic nervous system
      prevents unloading-induced bone loss by influencing leptin's skeletal effects and
      preventing transmission of loading information.

PMID- 21893224
TI  - Age as prognostic factor in patients with osteosarcoma.
AB  - Age at diagnosis is a well known prognostic factor in many different
      malignancies; its significance for patients with osteosarcoma is however
      controversial. To gain more insight in the prognostic role of age, we performed a
      retrospective study at our institute. We included 102 patients with de-novo
      osteosarcoma and formed three age groups to evaluate age specific survival rates:
      <= 14 years, 15-19 years and 20-40 years. Differences in outcome between patients
      aged 15-19 years treated at either the pediatric department or the adult
      department of oncology were evaluated. The 5-year overall survival rate (OSR) of
      the whole population was 53.5%+/-1.5%. OSR of 70.6%+/-0.8% was seen in patients
      <= 14 years old, 52.5%+/-1.1% in patients 15-19 years old and 33.3%+/-0.9% in the
      patients aged 20-40 years (p=0.01). Significant differences were observed with
      regard to stage at presentation (higher in older age groups), size of the tumor
      (larger in younger age groups) and histological response (more good responders in
      younger age groups). No significant difference was seen between outcomes of
      patients aged 15-19 years treated at the pediatric or adult oncology department.
      In conclusion, younger patients have a significantly better outcome than older
      patients.

PMID- 21893225
TI  - Effects of one year daily teriparatide treatment on trabecular bone material
      properties in postmenopausal osteoporotic women previously treated with
      alendronate or risedronate.
AB  - In the present work we examined the effect of teriparatide administration
      following bisphosphonate treatment on bone compositional properties by Raman and
      Fourier Transform Infrared Imaging (FTIR) microspectroscopic analysis. Thirty two
      paired iliac crest biopsies (before and after 1 year teriparatide) from sixteen
      osteoporotic women previously treated with either Alendronate (ALN) or
      Risedronate (RIS) and subsequently treated 12 months with teriparatide (TPTD)
      were analyzed at anatomical areas of similar tissue age in bone forming areas
      (within the fluorescent double labels). The outcomes that were monitored and
      reported were mineral to matrix ratio (corresponding to ash weight), mineral
      maturity (indicative of the mineral crystallite chemistry and stoichiometry, and
      having a direct bearing on crystallite shape and size), relative proteoglycan
      content (regulating mineralization commencement), and the ratio of two of the
      major enzymatic collagen cross-links (pyridinoline/divalent). Significant
      differences in mineral/matrix, mineral maturity/crystallinity, and collagen cross
      link ratio bone quality indices after TPTD treatment were observed, indicating a
      specific response of these patients to TPTD treatment. Moreover differences
      between ALN and RIS treated patients at baseline in the collagen cross-link ratio
      were observed. Since tissue areas of similar tissue age were analyzed, these
      differences may not be attributed to differences in bone turnover.

PMID- 21893226
TI  - Role of farnesoid X receptor (FXR) in the process of differentiation of bone
      marrow stromal cells into osteoblasts.
AB  - Bone tissue contains bile acids which accumulate from serum and which can be
      released in large amounts in the bone microenvironment during bone resorption.
      However, the direct effects of bile acids on bone cells remain largely
      unexplored. Bile acids have been identified as physiological ligands of the
      farnesoid X receptor (FXR, NR1H4). In the present study, we have examined the
      effects of FXR activation/inhibition on the osteoblastic differentiation of human
      bone marrow stromal cells (BMSC). We first demonstrated the expression of FXR in
      BMSC and SaOS2 osteoblast-like cells, and observed that FXR activation by
      chenodeoxycholic acid (CDCA) or by farnesol (FOH) increases the activity of
      alkaline phosphatase and the calcification of the extracellular matrix. In
      addition, we observed that FXR agonists are able to stimulate the expression of
      osteoblast marker genes [bone sialoprotein (BSP), osteocalcin (OC), osteopontin
      (OPN) and alkaline phosphatase (ALP)] (FXR involvement validated by shRNA-induced
      gene silencing), as well as the DNA binding activity of the bone transcription
      factor RUNX2 (EMSA and ChIP assay). Importantly, we observed that nitrogen
      containing bisphosphonates (BPs) inhibit the basal osteoblastic differentiation
      of BMSC, possibly through suppression of endogenous FOH production, independently
      of their effects on protein prenylation. Likewise, we found that the FXR
      antagonist guggulsterone (GGS) inhibits ALP activity, calcium deposition, DNA
      binding of RUNX2, and bone marker expression, indicating that GGS interferes with
      osteoblastic differentiation. Furthermore, GGS induced the appearance of lipid
      vesicles in BMSC and stimulated the expression of adipose tissue markers
      (peroxisome proliferator activated receptor-gamma (PPARgamma), adipoQ, leptin and
      CCAAT/enhancer-binding protein-alpha (C/EBPalpha)). In conclusion, our data
      support a new role for FXR in the modulation of osteoblast/adipocyte balance: its
      activation stimulates RUNX2-mediated osteoblastic differentiation of BMSC,
      whereas its inhibition leads to an adipocyte-like phenotype.

PMID- 21893227
TI  - [Radiotherapy and tinea capitis a 100 years ago].

PMID- 21893228
TI  - [Mycological and epidemiological aspects of tinea capitis in the Sousse region of
      Tunisia].
AB  - AIM: Tinea capitis continues to be considered a public health problem in Tunisia.
      The purpose of our study was to investigate trends in the incidence and the
      mycological and epidemiological aspects of tinea capitis in the Sousse region
      (Central Tunisia). METHOD: Our work is a retrospective study concerning all scalp
      samples taken by the parasitology laboratory of the Farhat Hached Hospital in
      Sousse, Tunisia, over a 26-year period (1983-2008). RESULTS: A total of 10,505
      specimens were examined. Of these, 5593 were positive with positive direct
      examination and/or positive culture. The average incidence was 215 cases per
      year. Patients were aged under 12 years in 89.3% of cases. A total of 175 cases
      of tinea capitis in adults were diagnosed. Ten dermatophyte species were
      isolated: Trichophyton (T.) violaceum (66.7%), Microsporum (M.) canis (29.3%), T.
      schoenleinii (1.6%), T. mentagrophytes (1.1%), T. verrucosum (0.6%), T. tonsurans
      (0.2%), T. rubrum (0.2%), M. gypseum (0.1%), M. audouinii (0.03%) and M. nanum
      (0.01%). CONCLUSION: Our study showed a decrease in the annual incidence of tinea
      capitis over the study period with an evident decrease in trichophytic tinea and
      disappearance of favus giving way to microsporic and inflammatory tinea.

PMID- 21893229
TI  - [Evaluation of information about prophylactic treatment and management of hand
      foot reactions caused by antiangiogenic therapies].
AB  - BACKGROUND: Antiangiogenic agents may be associated with severe hand-foot
      reactions (HFR) requiring dose adjustment by oncologists. Many preventive and
      curative treatments are described in the literature but their efficacy has not
      been assessed in clinical trials. The aim of this study was to examine
      information given to patients about HFR and to evaluate compliance with
      prophylactic therapy for this complication. PATIENTS AND METHODS: Fifty-one
      patients receiving antiangiogenic therapy were followed up for a period of 19
      months. At each visit, a dermatological examination was performed, compliance
      with topical treatment was assessed and advice was provided. At the end of the
      study, patients' perception of the information given was assessed by means of a
      questionnaire, completed either during consultations or by telephone. RESULTS:
      Although all patients were given information about HFR, 11 of 39 subjects claimed
      they had received no such information. There was no difference regarding
      compliance with topical treatment whether the information was provided by a
      dermatologist or an oncologist. Eleven patients consulted a podiatrist and nine
      patients used soft insoles. Twenty-two of 40 patients used topical treatments,
      with nine using such treatment from the outset. A statistically significant
      correlation was noted between compliance with preventive topical therapy and
      onset of HFR (P=0.028), and this finding merits confirmation in a larger-scale
      study. CONCLUSION: This study highlights the difficulties in implementing a
      programme to prevent HFR and suggests the value of providing multidisciplinary
      therapeutic education and of financing preventive and curative care.

PMID- 21893230
TI  - [Human amniotic membrane in the management of chronic venous leg ulcers].
AB  - BACKGROUND: The aim of our paper is to examine changes in the use of human
      amniotic membrane for venous leg ulcers through clinical studies and to present
      different models of tissue engineering employing human amniotic membrane for the
      purpose of future therapeutic use in wound healing. MATERIALS AND METHODS: This
      review is based on information obtained from a PubMed search using the following
      keywords "Amnion"[Mesh] AND "Leg Ulcer"[Mesh]; "Amnion"[Mesh] AND
      "Dermatology"[Mesh]. The selected articles are in English or French and deal with
      the sole use of human amniotic membrane in venous leg ulcers alone. RESULTS:
      Human amniotic membrane has a positive impact on chronic venous leg ulcers by
      promoting granulation tissue formation, reducing fibrosis and inducing re
      epithelialisation. Nevertheless, further randomized clinical studies are needed.
      At the same time, tissue engineering models using human amniotic membrane may
      help to reduce wound healing time, thereby creating renewed interest in the use
      of human amniotic membrane. CONCLUSION: Considering its properties and the
      clinical studies analysed, human amniotic membrane could be useful in venous leg
      ulcer care.

PMID- 21893231
TI  - [Auto-immune thyroiditis and drug reaction with eosinophilia and systemic
      symptoms (DRESS) associated with HHV-6 viral reactivation].
AB  - INTRODUCTION: DRESS syndrome is a severe adverse drug reaction with visceral
      involvement. Its physiopathology includes immunological disorders associated with
      human herpes virus (HHV) reactivation. We report two cases of auto-immune
      thyroiditis occurring in the context of DRESS syndrome associated with HHV-6
      reactivation. OBSERVATIONS: Case 1 : A 39-year-old woman presented DRESS syndrome
      with HHV-6 reactivation, cutaneous, lymph node, hepatic and renal disorders
      treated with systemic corticosteroids for 10 months. Following discontinuation of
      the corticosteroids, she developed Graves's disease, which was stabilized with
      carbimazole and a beta-blocker. CASE 2: A 31-year-old woman was hospitalized for
      DRESS syndrome with delayed HHV-6 reactivation and severe hepatic involvement.
      She was successfully treated by topical steroids. Six weeks later, she presented
      De Quervain thyroiditis associated with moderate relapsing DRESS, which were
      treated by sodium levothyroxine and topical steroids. DISCUSSION: There is
      currently debate about the implication of viral reactivation, in particular HHV
      6, in chronic DRESS, relapse and development of auto-immune diseases. These
      observations highlight the potential risk of patients developing auto-immune
      diseases and underline the need for prolonged clinical and laboratory follow-up
      of patients with DRESS.

PMID- 21893232
TI  - [Spontaneous remission of congenital leukemia cutis].
AB  - BACKGROUND: Aleukaemic leukaemia--without blasts in the blood or the bone marrow-
      with isolated cutaneous manifestations has been very rarely reported since only
      seven patients have been described to date. The prognosis is variable, and the
      indications for an aggressive treatment such as polychemotherapy are currently
      unclear. We report a case of spontaneously remitting aleukaemic leukaemia in a
      newborn child and compare it with other cases in the literature. CASE REPORT: A
      male newborn presented diffuse, violaceous skin nodules reminiscent of the so
      called "blueberry muffin syndrome" present since birth. Blood and marrow
      examinations did not show any blasts and karyotype was normal. Biopsy of a nodule
      established the diagnosis of acute myeloid leukaemia type 5. The course was
      spontaneously favourable despite the absence of specific therapy and the boy was
      asymptomatic after one year of follow-up. DISCUSSION: Of the eight reported
      infants (including ours), three died, including two through acute transformation
      of the leukaemia. The prognosis seems to be highly dependent on cytogenetic
      features with the 11q23 rearrangement being at higher risk of acute
      transformation, prompting recourse to aggressive chemotherapy. Our case further
      illustrates the favourable prognostic value of a normal karyotype, a situation in
      which therapeutic abstention seems possible, and is even recommended.

PMID- 21893233
TI  - [Lymphomatoid granulomatosis revealed by cutaneous lesions].
AB  - BACKGROUND: Lymphomatoid granulomatosis is a rare Epstein Barr virus (EBV)
      related lymphoproliferative disorder. It most frequently involves the lungs, skin
      and central nervous system and arises preferentially in patients with immune
      disorders. Here we report a case revealed by cutaneous lesions in an
      immunocompetent patient. CASE REPORT: A 56-year-old man consulted for
      erythematous nodules of the trunk associated with malaise and marked weight loss
      (14kg). In a few days the nodules became necrotic. Two weeks later a cough
      appeared and the chest computerized tomography showed multiple poorly defined
      nodular opacities with a peribronchovascular distribution. Cutaneous and
      pulmonary biopsies showed an infiltrate composed of medium-sized atypical
      lymphocytes T and B. EBV was present in the infiltrate (in situ hybridization)
      with a high EBV load in plasma. All of these data helped confirm the diagnosis of
      lymphoid granulomatosis. Despite aggressive treatment with polychemotherapy, the
      patient died after 2 months. DISCUSSION: Lymphomatoid granulomatosis represents a
      diagnostic challenge. In most cases, the presenting symptoms are not specific:
      malaise, weight loss, fever and cough. Moreover histology is difficult because of
      the T-cell-rich background. It is essential to consider this diagnosis in cases
      of cutaneous and pulmonary symptoms.

PMID- 21893234
TI  - [Dapsone efficacy in lupus miliaris disseminatus faciei: two cases].
AB  - BACKGROUND: Lupus miliaris disseminatum faciei (LMDF) is a rare, chronic and
      benign facial dermatosis that is regarded as an enigmatic diagnostic and
      therapeutic entity with spontaneous regression in 2 to 4 years leaving pock-like
      scars. CASE REPORT: We present two cases of LMDF: the first concerns a 46-year
      old woman who 6 months earlier presented a papular and pustular eruption on her
      face leaving small pitted scars. The inefficacy of treatment with cyclines,
      metronidazole and crotamiton as well as the clinical and histological examination
      results allowed a diagnosis of lupus miliaris disseminatus faciei to be made. The
      patient was placed on dapsone 100mg per day, which led to a remarkable
      improvement in the second week, but with depressed scars. The second case
      concerned an 18-year-old man who for 3 months had been presenting red-brown
      papules of the face that were resistant to cyclines and to topical retinoids and
      caused scarring. This clinical aspect, consolidated by the histological result,
      allowed the diagnosis of LMDF to be made. Administration of dapsone 100mg per day
      resulted in improvement from the first month, although there were residual
      cupuliform scars. DISCUSSION: Dapsone appears to be effective in the management
      of this disease, as illustrated in our two case reports. However, further studies
      are needed to confirm these results.

PMID- 21893236
TI  - [Sweet's syndrome revealing a lymph node tuberculosis].

PMID- 21893235
TI  - [An atypical presentation of primary cutaneous diffuse B-cell lymphoma, leg
      type].
AB  - BACKGROUND: Primary cutaneous diffuse B-cell lymphoma, leg type, are rare and
      aggressive tumours frequently affecting elderly patients. We present a case of a
      53-year-old woman with an atypical presentation of primary cutaneous diffuse B
      cell lymphoma, leg type. CASE REPORT: Eight years after complete excision of a
      Jessner-Kanof lymphocytic infiltration on the right shoulder, the patient
      developed a primary cutaneous diffuse B-cell lymphoma, leg type at the same site.
      The isolated lesion was treated using local radiotherapy. One year later, the
      patient presented headache associated with a temporal lesion, and biopsy
      confirmed a relapse. Cerebral CT scan showed an osteolytic temporal lesion while
      the other investigations revealed no extracutaneous extension. She was treated
      with R-CHOP chemotherapy and intrathecal methotrexate due to the osteolytic
      lesion. DISCUSSION: The particularity of this case consists in the age of this
      woman, who was younger than the average, the two atypical localizations on the
      shoulder, then the temple, and osteolysis, which is not the most frequent
      extension. Furthermore, to our knowledge, transformation of a Jessner-Kanof
      lesion into local aggressive primary cutaneous diffuse B-cell lymphoma, leg type,
      has not been yet described.

PMID- 21893237
TI  - [Sweet's syndrome following oral ciprofloxacin therapy].

PMID- 21893238
TI  - [Management of neuropathic pain in dermatology: in particularly post-zoster
      pain].

PMID- 21893239
TI  - [Eczema craquele].

PMID- 21893240
TI  - [Kimura disease].

PMID- 21893241
TI  - [Psoriasis: new susceptibility loci].

PMID- 21893242
TI  - [Primary palpebral amyloidosis].

PMID- 21893244
TI  - [Polymorphous light eruption caused by ultraviolet C light].

PMID- 21893243
TI  - [Chronic tubercular lupus].

PMID- 21893245
TI  - New frontiers in nitric oxide biology in plant.

PMID- 21893246
TI  - Methods of nitric oxide detection in plants: a commentary.
AB  - Over the last decade nitric oxide (NO) has been shown to influence a range of
      processes in plants. However, when, where and even if NO production occurs is
      controversial in several physiological scenarios in plants. This arises from a
      series of causes: (a) doubts have arisen over the specificity of widely used 4,5
      diaminofluorescein diacetate (DAF-2DA)/4-amino-5-methylamino-2,7
      difluorofluorescein (DAF-FM) dyes for NO, (b) no plant nitric oxide synthase
      (NOS) has been cloned, so that the validity of using mammalian NOS inhibitors to
      demonstrate that NO is being measured is debatable, (c) the NO scavenger 2-(4
      carboxyphenyl)-4,4,5,5-tetramethylimidazoline-l-oxyl-3-oxide (cPTIO) needs to be
      used with caution, and (d) some discrepancies between assays for in planta
      measurements and another based on sampling NO from the gas phase have been
      reported. This review will outline some commonly used methods to determine NO,
      attempt to reconcile differing results obtained by different laboratories and
      suggest appropriate approaches to unequivocally demonstrate the production of NO.

PMID- 21893247
TI  - The emerging roles of nitric oxide (NO) in plant mitochondria.
AB  - In recent years nitric oxide (NO) has been recognized as an important signal
      molecule in plants. Both, reductive and oxidative pathways and different
      subcellular compartments appear involved in NO production. The reductive pathway
      uses nitrite as substrate, which is exclusively generated by cytosolic nitrate
      reductase (NR) and can be converted to NO by the same enzyme. The mitochondrial
      electron transport chain is another site for nitrite to NO reduction, operating
      specifically when the normal electron acceptor, O(2), is low or absent. Under
      these conditions, the mitochondrial NO production contributes to hypoxic survival
      by maintaining a minimal ATP formation. In contrast, excessive NO production and
      concomitant nitrosative stress may be prevented by the operation of NO-scavenging
      mechanisms in mitochondria and cytosol. During pathogen attacks, mitochondrial NO
      serves as a nitrosylating agent promoting cell death; whereas in symbiotic
      interactions as in root nodules, the turnover of mitochondrial NO helps in
      improving the energy status similarly as under hypoxia/anoxia. The contribution
      of NO turnover during pathogen defense, symbiosis and hypoxic stress is discussed
      in detail.

PMID- 21893248
TI  - S-nitrosylation: an emerging post-translational protein modification in plants.
AB  - Increasing evidences support the assumption that nitric oxide (NO) acts as a
      physiological mediator in plants. Understanding its pleiotropic effects requires
      a deep analysis of the molecular mechanisms underlying its mode of action. In the
      recent years, efforts have been made in the identification of plant proteins
      modified by NO at the post-translational level, notably by S-nitrosylation. This
      reversible process involves the formation of a covalent bond between NO and
      reactive cysteine residues. This research has now born fruits and numerous
      proteins regulated by S-nitrosylation have been identified and characterized.
      This review describes the basic principle of S-nitrosylation as well as the
      Biotin Switch Technique and its recent adaptations allowing the identification of
      S-nitrosylated proteins in physiological contexts. The impact of S-nitrosylation
      on the structure/function of selected proteins is further discussed.

PMID- 21893249
TI  - Peroxynitrite formation and function in plants.
AB  - Peroxynitrite (ONOO(-)) is a reactive nitrogen species formed when nitric oxide
      (NO) reacts with the superoxide anion (O(2)(-)). It was first identified as a
      mediator of cell death in animals but was later shown to act as a positive
      regulator of cell signaling, mainly through the posttranslational modification of
      proteins by tyrosine nitration. In plants, peroxynitrite is not involved in NO
      mediated cell death and its physiological function is poorly understood. However,
      it is emerging as a potential signaling molecule during the induction of defense
      responses against pathogens and this could be mediated by the selective nitration
      of tyrosine residues in a small number of proteins. In this review we discuss the
      general role of tyrosine nitration in plants and evaluate recent evidence
      suggesting that peroxynitrite is an effector of NO-mediated signaling following
      pathogen infection.

PMID- 21893251
TI  - Nitric oxide signalling via cytoskeleton in plants.
AB  - Nitric oxide (NO) in plant cell mediates processes of growth and development
      starting from seed germination to pollination, as well as biotic and abiotic
      stress tolerance. However, proper understanding of the molecular mechanisms of NO
      signalling in plants has just begun to emerge. Accumulated evidence suggests that
      in eukaryotic cells NO regulates functions of proteins by their post
      translational modifications, namely tyrosine nitration and S-nitrosylation. Among
      the candidates for NO-downstream effectors are cytoskeletal proteins because of
      their involvement in many processes regulated by NO. This review discusses new
      insights in plant NO signalling focused mainly on the involvement of cytoskeleton
      components into NO-cascades. Herein, examples of NO-related post-translational
      modifications of cytoskeletal proteins, and also indirect NO impact, are
      discussed. Special attention is paid to plant alpha-tubulin tyrosine nitration as
      an emerging topic in plant NO research.

PMID- 21893250
TI  - GSNOR-mediated de-nitrosylation in the plant defence response.
AB  - A key feature of the plant defence response is the transient engagement of a
      nitrosative burst, resulting in the synthesis of reactive nitrogen intermediates
      (RNIs). Specific, highly reactive cysteine (Cys) residues of low pK(a) are a
      major site of action for these intermediates. The addition of an NO moiety to a
      Cys thiol to form an S-nitrosothiol (SNO), is termed S-nitrosylation. This redox
      based post-translational modification is emerging as a key regulator of protein
      function in plant immunity. Here we highlight recent advances in our
      understanding of de-nitrosylation, the mechanism that depletes protein SNOs, with
      a focus on S-nitrosoglutathione reductase (GSNOR). This enzyme controls total
      cellular S-nitrosylation indirectly during the defence response by turning over S
      nitrosoglutathione (GSNO), a major cache of NO bioactivity.

PMID- 21893252
TI  - Nitric oxide and ABA in the control of plant function.
AB  - Abscisic acid (ABA) and nitric oxide (NO) are both extremely important signalling
      molecules employed by plants to control many aspects of physiology. ABA has been
      extensively studied in the mechanisms which control stomatal movement as well as
      in seed dormancy and germination and plant development. The addition of either
      ABA or NO to plant cells is known to instigate the actions of many signal
      transduction components. Both may have an influence on the phosphorylation of
      proteins in cells mediated by effects on protein kinases and phosphatases, as
      well as recruiting a wide range of other signal transduction molecules to mediate
      the final effects. Both ABA and NO may also lead to the regulation of gene
      expression. However, it is becoming more apparent that NO may be acting
      downstream of ABA, with such action being mediated by reactive oxygen species
      such as hydrogen peroxide in some cases. However not all ABA responses require
      the action of NO. Here, examples of where ABA and NO have been put together into
      the same signal transduction pathways are discussed.

PMID- 21893253
TI  - The role of nitric oxide in the germination of plant seeds and pollen.
AB  - Two complex physiological processes, with opposite positions in the plant's life
      cycle, seed and pollen germination, are vital to the accomplishment of successful
      plant growth and reproduction. This review summarizes the current state of
      knowledge of the intersection of NO signalling with the signalling pathways of
      ABA, GA, and ethylene; plant hormones that control the release of plant seeds
      from dormancy and germination. The cross-talk of NO and ROS is involved in the
      light- and hormone-specific regulation of seeds' developmental processes during
      the initiation of plant ontogenesis. Similarly to seed germination, the
      mechanisms of plant pollen hydration, germination, tube growth, as well as pollen
      stigma recognition are tightly linked to the proper adjustment of NO and ROS
      levels. The interaction of NO with ROS and secondary messengers such as Ca(2+),
      cAMP and cGMP discovered in pollen represent a common mechanism of NO signalling.
      The involvement of NO in both breakpoints of plant physiology, as well as in the
      germination of spores within fungi and oomycetes, points toward NO as a component
      of an evolutionary conserved signalling pathway.

PMID- 21893254
TI  - Nitric oxide in legume-rhizobium symbiosis.
AB  - Nitric oxide (NO) is a gaseous signaling molecule with a broad spectrum of
      regulatory functions in plant growth and development. NO has been found to be
      involved in various pathogenic or symbiotic plant-microbe interactions. During
      the last decade, increasing evidence of the occurrence of NO during legume
      rhizobium symbioses has been reported, from early steps of plant-bacteria
      interaction, to the nitrogen-fixing step in mature nodules. This review focuses
      on recent advances on NO production and function in nitrogen-fixing symbiosis.
      First, the potential plant and bacterial sources of NO, including NO synthase
      like, nitrate reductase or electron transfer chains of both partners, are
      presented. Then responses of plant and bacterial cells to the presence of NO are
      presented in the context of the N(2)-fixing symbiosis. Finally, the roles of NO
      as either a regulatory signal of development, or a toxic compound with inhibitory
      effects on nitrogen fixation, or an intermediate involved in energy metabolism,
      during symbiosis establishment and nodule functioning are discussed.

PMID- 21893255
TI  - Nitric oxide, nitrosyl iron complexes, ferritin and frataxin: a well equipped
      team to preserve plant iron homeostasis.
AB  - Iron is a key element in plant nutrition. Iron deficiency as well as iron
      overload results in serious metabolic disorders that affect photosynthesis,
      respiration and general plant fitness with direct consequences on crop
      production. More than 25% of the cultivable land possesses low iron availability
      due to high pH (calcareous soils). Plant biologists are challenged by this
      concern and aimed to find new avenues to ameliorate plant responses and keep iron
      homeostasis under control even at wide range of iron availability in various
      soils. For this purpose, detailed knowledge of iron uptake, transport, storage
      and interactions with cellular compounds will help to construct a more complete
      picture of its role as essential nutrient. In this review, we summarize and
      describe the recent findings involving four central players involved in keeping
      cellular iron homeostasis in plants: nitric oxide, ferritin, frataxin and
      nitrosyl iron complexes. We attempt to highlight the interactions among these
      actors in different scenarios occurring under iron deficiency or iron overload,
      and discuss their counteracting and/or coordinating actions leading to the
      control of iron homeostasis.

PMID- 21893256
TI  - Polyamines, polyamine oxidases and nitric oxide in development, abiotic and
      biotic stresses.
AB  - Nitric oxide (NO), polyamines (PAs), diamine oxidases (DAO) and polyamine
      oxidases (PAO) play important roles in wide spectrum of physiological processes
      such as germination, root development, flowering and senescence and in defence
      responses against abiotic and biotic stress conditions. This functional
      overlapping suggests interaction of NO and PA in signalling cascades. Exogenous
      application of PAs putrescine, spermidine and spermine to Arabidopsis seedlings
      induced NO production as observed by fluorimetry and fluorescence microscopy
      using the NO-binding fluorophores DAF-2 and DAR-4M. The observed NO release
      induced by 1 mM spermine treatment in the Arabidopsis seedlings was very rapid
      without apparent lag phase. These observations pave a new insight into PA
      mediated signalling and NO as a potential mediator of PA actions. When comparing
      the functions of NO and PA in plant development and abiotic and biotic stresses
      common to both signalling components it can be speculated that NO may be a link
      between PA-mediated stress responses filing a gap between many known
      physiological effects of PAs and amelioration of stresses. NO production
      indicated by PAs could be mediated either by H(2)O(2), one reaction product of
      oxidation of PAs by DAO and PAO, or by unknown mechanisms involving PAs, DAO and
      PAO.

PMID- 21893257
TI  - Nitric oxide imbalance provokes a nitrosative response in plants under abiotic
      stress.
AB  - Nitric oxide (NO), a free radical generated in plant cells, belongs to a family
      of related molecules designated as reactive nitrogen species (RNS). When an
      imbalance of RNS takes place for any adverse environmental circumstances, some of
      these molecules can cause direct or indirect damage at the cellular or molecular
      level, promoting a phenomenon of nitrosative stress. Thus, this review will
      emphasize the recent progress in understanding the function of NO and its
      production under adverse environmental conditions.

PMID- 21893258
TI  - The message of nitric oxide in cadmium challenged plants.
AB  - During the last decade it has been found that cadmium (Cd), one of the most toxic
      elements occurring in polluted environments, interferes with nitric oxide (NO), a
      multifunctional signaling molecule in living organisms. The formation of NO has
      been demonstrated in vivo in various plant tissues exposed to Cd stress, but
      unfortunately, the time and intensity of NO generation, relatively frequently
      shows conflicting data. What is more, there is still limited information
      regarding the functional role of endogenously produced NO in plants challenged
      with heavy metals. The first pharmacological approaches revealed that exogenously
      applied NO can alleviate cadmium toxicity in plants, promoting the direct
      scavenging of reactive oxygen species (ROS) or activating antioxidant enzymes.
      However, recent reports have indicated that NO even contributes to Cd toxicity by
      promoting Cd uptake and participates in metal-induced reduction of root growth.
      In view of this heterogeneous knowledge, much more puzzling if we consider
      results first obtained using exogenous NO sources, this review is focused mainly
      on the implication of endogenous NO in plant response to Cd exposure.
      Furthermore, a basic draft for NO mode of action during cadmium stress is
      proposed.

PMID- 21893259
TI  - [Treatment of intraocular-pressure-independent phenomena in pseudoexfoliation
      syndrome].

PMID- 21893260
TI  - [Automatic detection of microaneurysms in colour fundus images].
AB  - PURPOSE: We present the development of a tool for the automatic detection of
      microaneurysms and its clinical evaluation. The intention of this tool is to
      facilitate the diagnosis of diabetic retinopathy in general screening programs.
      METHOD: The designed and developed tool consists of three stages of processing:
      1) Obtaining of the basic image of eye with the retinal camera, inverted image on
      the green channel, and a high-pass filter of the image. This phase enhances the
      microaneurysms. 2) Detection of the candidates for microaneurysms, by means of an
      adaptive prediction filter and regions growth. 3) Selection, among the
      candidates, of whom microaneurysms must be considered to fulfil the criteria of
      circular shape, high intensity in the inverted green channel and contrasts with
      respect to the surrounding pixels. RESULTS: We selected to 20 retinal photographs
      of good quality and dimensions 600x600 pixels from patients with nonproliferative
      diabetic retinopathy. The ophthalmologists detected 297 microaneurysms in these
      images. The tool for automatic detection correctly located 252 microaneurysms,
      with a mean sensitivity of 89% and a false positives rate of 93%. CONCLUSIONS:
      The results obtained seem to indicate that the tool developed will be very useful
      for its potential use in screening programs in primary care centres. On the other
      hand, more work is needed on the algorithm to decrease the rate of false
      positives.

PMID- 21893261
TI  - [The influence of the Travalert((r)) dosing aid on medical treatment compliance
      and the quality of life of glaucoma patients].
AB  - PURPOSE: To study compliance in the medical treatment of glaucoma, its possible
      association with other factors, and quality of life of patients with glaucoma.
      MATERIAL AND METHODS: Longitudinal prospective study of 60 patients with ocular
      hypertension or glaucoma who were treated with travoprost, or with a fixed
      combination of travoprost/timolol nightly. All subjects were given a
      Travalert((r)) dosing aid and were reviewed after one and four months. Strict and
      relative compliance data were collected on each visit. The relationship between
      compliance and other variables was studied using univariate analysis. To analyse
      quality of life, patients were given self-assessment STAI anxiety questionnaires
      after the first and last visits. RESULTS: Relative compliance for the four months
      was significantly greater than the strict compliance (P=.001). In the group of
      least compliance the number of patients on treatment with combination therapy was
      significantly higher than those on monotherapy. In the lost cases, the number of
      men was significantly higher than women. No association was found in the other
      variables. The anxiety was similar to that in the normal population. CONCLUSIONS:
      Compliance is very important in the treatment of glaucoma, and our study provides
      objective data through the use of Travalert dosing aid with relative compliances
      of 70%. Patients with combined therapies have lower compliance than those on
      monotherapy.

PMID- 21893262
TI  - [Comparison of Goldmann applanation and dynamic contour tonometry measurements:
      effects of corneal morphometry].
AB  - OBJECTIVES: To compare intraocular pressure (IOP) measurements made by Goldmann
      applanation tonometry (GAT) and dynamic contour tonometry (DCT). METHODS: IOPs
      were measured by GAT and DCT in 63 eyes of 63 healthy subjects. A comparison was
      made by intraclass correlation coefficient. Passing-Bablok plot was constructed
      to establish the existence of systematic and/or proportional biases. Multivariate
      regression analysis was used to examine whether the measurements of both
      instruments were affected by the power of the steepest and flattest corneal axes,
      their orientation, age or central corneal thickness (CCT). RESULTS: The intra
      class correlations (ICCs) were 0.57 (95% confidence interval (95% CI): 0.29
      0.74). Mean differences were 1.68 (DCT minus GAT) (95% CI: 0.92-2.44). Passing
      Bablok analysis (X=DCT, Y=GAT) revealed a systematic bias (A=-14.35, 95% CI: 
      24.51-[-9.14]) and a proportional bias (B=1.74, 95% CI: 1.43-2.26). Multivariate
      regression analysis revealed that the DCT was independent of the corneal
      characteristics analysed while GAT was biased by CCT (B=0.042, 95% CI: 0.002
      0.082). CONCLUSIONS: While GAT was biased by corneal CCT; DCT readings were
      independent of corneal morphometry.

PMID- 21893263
TI  - [Hereditary glaucoma associated with oculodentodigital dysplasia].
AB  - CASE REPORT: A newborn evaluated at 20 days old due to occasional nystagmus. Her
      mother had presented with oculodentodigital dysplasia (ODDD) and glaucoma. The
      physical examination revealed opaque micro-corneas, and horizontal nystagmus. The
      tonometry showed 35 mm Hg in OD and 40 mm Hg in OS and the fundus examination was
      normal. She had a narrow nasal bridge with narrow nostrils, and fourth and fifth
      finger syndactylyl in both hands. A bilateral trabeculectomy was performed with a
      good response. DISCUSSION: ODDD is a rare autosomal dominant disease with
      heterogeneous phenotype manifestations. The most frequent cause of loss of visual
      acuity is the glaucoma, requiring long-term follow up with periodical control of
      the intraocular pressure (IOP).

PMID- 21893264
TI  - [Retinal detachment associated with morning glory syndrome].
AB  - CASE REPORT: A twenty three year old woman was diagnosed of a morning glory
      papillary anomaly, then with normal visual acuity (VA). Nine years later, the VA
      decreased to 0.4, secondary to a serous macular detachment, confirmed by optical
      coherence tomography (OCT). After treatment with C2F6 gas injection, positioning,
      and peripapillary laser, the VA improved to 0.7 and the foveolar area reattached.
      DISCUSSION: The morning glory Syndrome usually has an early diagnosis due to poor
      visual acuity. Thirty eight percent of the cases have retinal detachment. We show
      an unusual case of morning glory syndrome with a serous detachment, successfully
      treated with gas and laser.

PMID- 21893265
TI  - [Pupillary block acute glaucoma due to acrylic intraocular lens posterior
      dislocation after Nd:YAG capsulotomy].
AB  - CASE REPORT: We present the clinical case of a 68 year-old woman who developed a
      pupillary block acute glaucoma due to vitreous hernia into anterior chamber
      following posterior dislocation of the intraocular lens one month after an Nd:YAG
      capsulotomy. DISCUSSION: We should consider these symptoms in the differential
      diagnosis of pseudophakic acute glaucoma, especially when visualisation of the
      anterior chamber is difficult due to corneal oedema and Nd:YAG capsulotomy was
      done.

PMID- 21893266
TI  - [The eyes of the Catalan Roman].

PMID- 21893267
TI  - [Phototoxicity: ultraviolet radiation and cataracts].

PMID- 21893268
TI  - Hepatology update: current management and new therapies.

PMID- 21893270
TI  - Hepatitis B: modern end points of treatment and the specter of viral resistance.
AB  - The goal of antiviral treatment of chronic hepatitis B is to prevent the
      complications of cirrhosis, hepatic decompensation, HCC, and death. Because these
      clinical outcomes may take a long period of time to develop, it is important to
      use intermediate or surrogate end points to evaluate the efficacy and response to
      antiviral treatment, and to determine whether treatment can be safely stopped,
      especially given concern for the development of antiviral resistance with NUC
      therapy. Although normalization of ALT and suppression of HBV DNA viral
      replication are associated with favorable outcomes, the durability of their
      response is low, and these end points are insufficient markers for stopping
      treatment. HBeAg seroconversion is currently used to discontinue NUC treatment in
      patients with HBeAg-positive chronic hepatitis B, whereas the stopping rule for
      HBeAg-negative disease relies on HBsAg loss. However, HBsAg loss occurs very
      infrequently and is not a practical end point for clinical use, although
      quantitative HBsAg levels may be useful in identifying patients who could achieve
      a sustained virologic response to treatment.

PMID- 21893269
TI  - Emerging therapies in hepatitis C: dawn of the era of the direct-acting
      antivirals.
AB  - The HCV viral life cycle provides targets for drug development at virtually every
      step, and many new drugs aimed at these targets are currently being developed.
      Clinical practice takes a major step forward this year with the arrival of
      telaprevir and boceprevir, which will be added to the current standard of care of
      pegIFNalpha/RBV. Patients will need to be monitored closely and counseled
      extensively, and clinicians will need to learn the new response-guided therapy
      algorithms with these therapies. Although there remains work to be done in the
      field of HCV, these therapies will allow many more patients the opportunity to
      eradicate HCV infection.

PMID- 21893271
TI  - Noninvasive tools to assess hepatic fibrosis: ready for prime time?
AB  - Often regarded as the gold standard for fibrosis assessment, liver biopsy carries
      associated risks; however, it is less than ideal. The need for noninvasive
      assessment of hepatic fibrosis for disease staging, prognosis, progression, and
      treatment response is clear. Advances in serologic testing and conventional
      imaging techniques have reduced the need for liver biopsy. Areas of research
      include defining cutoff values for specific diseases, further head-to-head
      comparisons of noninvasive modalities, examination of algorithms using both serum
      markers and imaging, and the cost-effectiveness of these various tests for
      diagnostic as well as screening purposes.

PMID- 21893272
TI  - Acute liver failure: current practice and recent advances.
AB  - ALF is an important cause of liver-related morbidity and mortality. Advances in
      the management of ICH and SIRS, and cardiorespiratory, metabolic, and renal
      support have improved the outlook of such patients. Early transfer to a liver
      transplant center is essential. Routine use of NAC is recommended for patients
      with early hepatic encephalopathy, irrespective of the etiology. The role of
      hypothermia remains to be determined. Liver transplantation plays a critical
      role, particularly for those with advanced encephalopathy. Several detoxification
      and BAL support systems have been developed to serve as a bridge to
      transplantation or to spontaneous recovery. However, such systems lack sufficient
      reliability and efficacy to be applied routinely in clinical practice. Hepatocyte
      and stem cell transplantation may provide valuable adjunctive therapy in the
      future.

PMID- 21893273
TI  - Nonalcoholic fatty liver disease: pharmacologic and surgical options.
AB  - The last decade has seen many studies examining the prevalence and natural
      history of NAFLD in the United States and it is clear that this disease is likely
      to be an important cause of liver-related morbidity in the future. Several
      pharmacologic therapies have shown some promise; currently, vitamin E and insulin
      sensitizing agents such as pioglitazone can be considered in appropriate cases.
      Conservative measures to promote weight loss still have a role to play, but the
      obesity epidemic in the Western World has reached such proportions that bariatric
      surgery is proving to be an attractive option for patients with a BMI greater
      than 35 to 40 kg/m2. Well-designed prospective studies are required to ensure
      that all of these therapies are safe and effective in the long term. Newer agents
      will likely be investigated as the pathogenesis of NAFLD and fibrosis progression
      in NASH are further elucidated.

PMID- 21893274
TI  - Managing varices: drugs, bands, and shunts.
AB  - Drugs, bands, and shunts have all been used in the treatment of varices and
      variceal hemorrhage and have resulted in improved outcomes. However, the specific
      use of each of these therapies depends on the setting (primary or secondary
      prophylaxis, treatment of AVH) and on patient characteristics. The indications
      for each are summarized in Table 4.

PMID- 21893275
TI  - Hepatorenal syndrome: do the vasoconstrictors work?
AB  - The development of hepatorenal syndrome (HRS) is related to many changes
      associated with advanced cirrhosis. Because vasoconstrictors correct systemic and
      splanchnic hemodynamic abnormalities, they are effective treatments for HRS,
      although only in approximately 40% of HRS patients. Emerging data show that
      combination treatment with vasoconstrictors and TIPS may yield better outcomes
      than either alone. All HRS patients should be assessed for liver transplantation.
      Reversing HRS before transplantation is associated with better long-term
      survival. Combined liver- kidney transplantation is indicated for those with
      irreversible kidney injury. Otherwise, there is some merit in performing a liver
      transplant first and only considering a kidney transplant later.

PMID- 21893276
TI  - Hepatocellular carcinoma: locoregional and targeted therapies.
AB  - HCC is a leading cause of morbidity and mortality worldwide. Advances in cancer
      screening and surveillance have allowed for earlier detection of tumors,
      affording greater treatment potential. The advent of locoregional therapies has
      generated greater treatment options for patients with HCC. Either alone or in
      combination as an adjuvant or neoadjuvant therapy, these novel approaches
      continue to hold promise for improving morbidity and/or mortality of patients
      with HCC. The emergence of systemic molecular targeted therapies increases the
      role of translational science. Whereas surgical resection and transplantation
      conventionally form the cornerstone of curative approaches, the advancement of
      locoregional therapies holds great promise in adding to the curative
      armamentarium.

PMID- 21893277
TI  - Alcoholic hepatitis: prognostic models and treatment.
AB  - Alcoholic hepatitis is a distinct subset of alcoholic liver disease. Inflammation
      and oxidative stress are the two main pathogenetic mechanisms involved in its
      pathogenesis. Patients with mild disease usually improve with conservative
      management. However, about 30-50% of those with severe disease succumb to their
      illness within about 1 month. Therefore, assessment of disease severity is
      important and practical issue. Currently, hepatologists do not have an ideal
      scoring system available. With survival benefit of only about 50% with
      corticosteroids and pentoxifylline, there is need to develop newer and better
      treatment options to manage these patients. This article also deals with
      controversies surrounding the role and use of liver transplantation in patients
      with alcoholic hepatitis.

PMID- 21893278
TI  - Liver transplantation in the 21st century: expanding the donor options.
AB  - Over the past decade, use of ECD organs for OLT has allowed many transplant
      programs to afford patients access to an otherwise scarce resource and to
      maintain center volume. Although overall posttransplant outcomes are inferior to
      results with optimal, whole-liver grafts, aggressive utilization of ECD and DCD
      organs significantly lowers median wait-times for OLT, MELD score at OLT, and
      death while awaiting transplantation. It is incumbent on the transplant community
      to provide continued scrutiny of the many factors involved in ECD organ
      utilization, evaluate the degree of risk and benefit such allografts may impart
      on particular recipients, and thereby provide suitable "matching" to maximize
      favorable outcomes. Transplant caregivers need to provide patients with evidence
      based care decisions, be good stewards of a scarce resource, and maintain
      threshold survival results for their programs. This requires balancing the
      urgency with which a transplant is needed and the utility of such a transplant.
      There is a clear necessity to pursue additional donor research to improve use of
      these marginal grafts and assess interventions that enhance the safety of ECD
      livers.

PMID- 21893279
TI  - Long-term management of the liver transplant recipient: pearls for the practicing
      gastroenterologist.
AB  - Liver transplantation is becoming more common and patients are surviving longer
      after transplantation. Special care must be paid to the long-term management of
      these patients because they are at increased risk for medical problems,
      malignancies, and adverse effects from immunosuppression. A stable and continuing
      relationship must be developed between the physician and the patient to optimize
      the long-term outcomes for these individuals.

PMID- 21893280
TI  - Ribonuclease J: how to lead a double life.

PMID- 21893281
TI  - Trapping small caffeine in a large GPCR pocket.

PMID- 21893282
TI  - Assembling good amyloid: some structures at last.

PMID- 21893283
TI  - Symmetry-restrained flexible fitting for symmetric EM maps.
AB  - Many large biological macromolecules have inherent structural symmetry, being
      composed of a few distinct subunits, repeated in a symmetric array. These
      complexes are often not amenable to traditional high-resolution structural
      determination methods, but can be imaged in functionally relevant states using
      cryo-electron microscopy (cryo-EM). A number of methods for fitting atomic-scale
      structures into cryo-EM maps have been developed, including the molecular
      dynamics flexible fitting (MDFF) method. However, quality and resolution of the
      cryo-EM map are the major determinants of a method's success. In order to
      incorporate knowledge of structural symmetry into the fitting procedure, we
      developed the symmetry-restrained MDFF method. The new method adds to the cryo-EM
      map-derived potential further restraints on the allowed conformations of a
      complex during fitting, thereby improving the quality of the resultant structure.
      The benefit of using symmetry-based restraints during fitting, particularly for
      medium to low-resolution data, is demonstrated for three different systems.

PMID- 21893284
TI  - RNA tertiary interactions in a riboswitch stabilize the structure of a kink turn.
AB  - The kink turn is a widespread RNA motif that introduces an acute kink into the
      axis of duplex RNA, typically comprising a bulge followed by a G?A and A?G pairs.
      The kinked conformation is stabilized by metal ions, or the binding of proteins
      including L7Ae. We now demonstrate a third mechanism for the stabilization of k
      turn structure, involving tertiary interactions within a larger RNA structure.
      The SAM-I riboswitch contains an essential standard k-turn sequence that kinks a
      helix so that its terminal loop can make a long-range interaction. We find that
      some sequence variations in the k-turn within the riboswitch do not prevent SAM
      binding, despite preventing the folding of the k-turn in isolation. Furthermore,
      two crystal structures show that the sequence-variant k-turns are conventionally
      folded within the riboswitch. This study shows that the folded structure of the k
      turn can be stabilized by tertiary interactions within a larger RNA structure.

PMID- 21893285
TI  - Unusual, dual endo- and exonuclease activity in the degradosome explained by
      crystal structure analysis of RNase J1.
AB  - RNase J is an essential enzyme in Bacillus subtilis with unusual dual
      endonuclease and 5'-to-3' exonuclease activities that play an important role in
      the maturation and degradation of mRNA. RNase J is also a component of the
      recently identified "degradosome" of B. subtilis. We report the crystal structure
      of RNase J1 from B. subtilis to 3.0 A resolution, analysis of which reveals it to
      be in an open conformation suitable for binding substrate RNA. RNase J is a
      member of the beta-CASP family of zinc-dependent metallo-beta-lactamases. We have
      exploited this similarity in constructing a model for an RNase J1:RNA complex.
      Analysis of this model reveals candidate-stacking interactions with conserved
      aromatic side chains, providing a molecular basis for the observed enzyme
      activity. Comparisons of the B. subtilis RNase J structure with related enzymes
      reveal key differences that provide insights into conformational changes during
      catalysis and the role of the C-terminal domain.

PMID- 21893286
TI  - Molecular basis for the recognition and cleavage of RNA by the bifunctional 5'-3'
      exo/endoribonuclease RNase J.
AB  - RNase J is a key member of the beta-CASP family of metallo-beta-lactamases
      involved in the maturation and turnover of RNAs in prokaryotes. The B. subtilis
      enzyme possesses both 5'-3' exoribonucleolytic and endonucleolytic activity, an
      unusual property for a ribonuclease. Here, we present the crystal structure of T.
      thermophilus RNase J bound to a 4 nucleotide RNA. The structure reveals an RNA
      binding channel that illustrates how the enzyme functions in 5'-3'
      exoribonucleolytic mode and how it can function as an endonuclease. A second,
      negatively charged tunnel leads from the active site, and is ideally located to
      evacuate the cleaved nucleotide in 5'-3' exonucleolytic mode. We show that B.
      subtilis RNase J1, which shows processive behavior on long RNAs, behaves
      distributively for substrates less than 5 nucleotides in length. We propose a
      model involving the binding of the RNA to the surface of the beta-CASP domain to
      explain the enzyme's processive action.

PMID- 21893287
TI  - Quantitative analysis of the interaction strength and dynamics of human IgG4 half
      molecules by native mass spectrometry.
AB  - Native mass spectrometry (MS) is a powerful technique for studying noncovalent
      protein-protein interactions. Here, native MS was employed to examine the
      noncovalent interactions involved in homodimerization of antibody half molecules
      (HL) in hinge-deleted human IgG4 (IgG4Deltahinge). By analyzing the concentration
      dependence of the relative distribution of monomer HL and dimer (HL)(2) species,
      the apparent dissociation constant (K(D)) for this interaction was determined. In
      combination with site-directed mutagenesis, the relative contributions of
      residues at the CH3-CH3 interface to this interaction could be characterized and
      corresponding K(D) values quantified over a range of 10(-10)-10(-4) M. The
      critical importance of this noncovalent interaction in maintaining the intact
      dimeric structure was also proven for the full-length IgG4 backbone. Using time
      resolved MS, the kinetics of the interaction could be measured, reflecting the
      dynamics of IgG4 HL exchange. Hence, native MS has provided a quantitative view
      of local structural features that define biological properties of IgG4.

PMID- 21893288
TI  - Structural basis for complex formation between human IRSp53 and the translocated
      intimin receptor Tir of enterohemorrhagic E. coli.
AB  - Actin assembly beneath enterohemorrhagic E. coli (EHEC) attached to its host cell
      is triggered by the intracellular interaction of its translocated effector
      proteins Tir and EspF(U) with human IRSp53 family proteins and N-WASP. Here, we
      report the structure of the N-terminal I-BAR domain of IRSp53 in complex with a
      Tir-derived peptide, in which the homodimeric I-BAR domain binds two Tir
      molecules aligned in parallel. This arrangement provides a protein scaffold
      linking the bacterium to the host cell's actin polymerization machinery. The
      structure uncovers a specific peptide-binding site on the I-BAR surface,
      conserved between IRSp53 and IRTKS. The Tir Asn-Pro-Tyr (NPY) motif, essential
      for pedestal formation, is specifically recognized by this binding site. The site
      was confirmed by mutagenesis and in vivo-binding assays. It is possible that
      IRSp53 utilizes the NPY-binding site for additional interactions with as yet
      unknown partners within the host cell.

PMID- 21893289
TI  - Atomic resolution insights into curli fiber biogenesis.
AB  - Bacteria produce functional amyloid fibers called curli in a controlled,
      noncytotoxic manner. These extracellular fimbriae enable biofilm formation and
      promote pathogenicity. Understanding curli biogenesis is important for
      appreciating microbial lifestyles and will offer clues as to how disease
      associated human amyloid formation might be ameliorated. Proteins encoded by the
      curli specific genes (csgA-G) are required for curli production. We have
      determined the structure of CsgC and derived the first structural model of the
      outer-membrane subunit translocator CsgG. Unexpectedly, CsgC is related to the N
      terminal domain of DsbD, both in structure and oxido-reductase capability.
      Furthermore, we show that CsgG belongs to the nascent class of helical outer
      membrane macromolecular exporters. A cysteine in a CsgG transmembrane helix is a
      potential target of CsgC, and mutation of this residue influences curli assembly.
      Our study provides the first high-resolution structural insights into curli
      biogenesis.

PMID- 21893291
TI  - Characterization of the structure and function of Escherichia coli DegQ as a
      representative of the DegQ-like proteases of bacterial HtrA family proteins.
AB  - HtrA family proteins play a central role in protein quality control in the
      bacterial periplasmic space. DegQ-like proteases, a group of bacterial HtrA
      proteins, are characterized by a short LA loop as compared with DegP-like
      proteases, and are found in many bacterial species. As a representative of the
      DegQ-like proteases, we report that Escherichia coli DegQ exists in vivo
      primarily as a trimer (substrate-free) or dodecamer (substrate-containing).
      Biochemical analysis of DegQ dodecamers revealed that the major copurified
      protein substrate is OmpA. Importantly, wild-type DegQ exhibited a much lower
      proteolytic activity, and thus higher chaperone-like activity, than DegP.
      Furthermore, using cryo-electron microscopy we determined high-resolution
      structures of DegQ 12- and 24-mers in the presence of substrate, thus revealing
      the structural mechanism by which DegQ moderates its proteolytic activity.

PMID- 21893290
TI  - Crystal structure of cGMP-dependent protein kinase reveals novel site of
      interchain communication.
AB  - The cGMP-dependent protein kinase (PKG) serves as an integral component of second
      messenger signaling in a number of biological contexts including cell
      differentiation, memory, and vasodilation. PKG is homodimeric and large
      conformational changes accompany cGMP binding. However, the structure of PKG and
      the molecular mechanisms associated with protomer communication following cGMP
      induced activation remain unknown. Here, we report the 2.5 A crystal structure of
      a regulatory domain construct (aa 78-355) containing both cGMP binding sites of
      PKG Ialpha. A distinct and segregated architecture with an extended central helix
      separates the two cGMP binding domains. Additionally, a previously
      uncharacterized helical domain (switch helix) promotes the formation of a
      hydrophobic interface between protomers. Mutational disruption of this
      interaction in full-length PKG implicates the switch helix as a critical site of
      dimer communication in PKG biology. These results offer new structural insight
      into the mechanism of allosteric PKG activation.

PMID- 21893293
TI  - Monoenergetic imaging of dual-energy CT reduces artifacts from implanted metal
      orthopedic devices in patients with factures.
AB  - RATIONALE AND OBJECTIVES: The purpose of this study was to optimize photon energy
      setting to reduce metal artifact of computed tomography (CT) images from
      implanted metal orthopedic devices in patients with fractures with monoenergetic
      imaging of dual-energy CT. MATERIALS AND METHODS: This study included 47 patients
      with factures who underwent metal orthopedic device implanting. After dual-energy
      CT scan, monoenergetic software was used to postprocess with the following six
      photon energies: 40 kiloelectron-voltage (keV), 70 keV, 100 keV, 130 keV, 160
      keV, and 190 keV. Two radiologists evaluated and rated the reformatted images
      with six different photon energies and average weighted 120 kVp images according
      to 4-score scale. The Wilcoxon rank-sum test was used to compare image quality
      scores for total, internal, and external metal orthopedic devices. Interreader
      agreement for image quality scoring was calculated. RESULTS: Monoenergetic
      imaging of dual-energy CT improved the quality of CT images in the fracture
      patients with metal orthopedic devices compared to the average weighted 120 kVp
      images for the total, external, and internal metal orthopedic devices (all P
      values < .01). Optimal keV setting with the lowest metal artifact was 130 keV for
      total, internal, and external metal orthopedic devices. Good interreader
      agreement was found for the evaluation of image quality for total, internal, and
      external metal orthopedic devices. CONCLUSIONS: Monoenergetic imaging of dual
      energy CT improves quality of CT images in patients with metal orthopedic devices
      after fracture. Reformatted images at 130 keV have the optimal quality for total,
      internal, and external metal orthopedic devices.

PMID- 21893292
TI  - Biophysical and computational studies of membrane penetration by the GRP1
      pleckstrin homology domain.
AB  - The pleckstrin homology (PH) domain of the general receptor for phosphoinositides
      1 (GRP1) exhibits specific, high-affinity, reversible binding to
      phosphatidylinositol (3,4,5)-trisphosphate (PI(3,4,5)P(3)) at the plasma
      membrane, but the nature and extent of the interaction between this bound complex
      and the surrounding membrane environment remains unclear. Combining equilibrium
      and nonequilibrium molecular dynamics (MD) simulations, NMR spectroscopy, and
      monolayer penetration experiments, we characterize the membrane-associated state
      of GRP1-PH. MD simulations show loops flanking the binding site supplement the
      interaction with PI(3,4,5)P(3) through multiple contacts with the lipid bilayer.
      NMR data show large perturbations in chemical shift for these loop regions on
      binding to PI(3,4,5)P(3)-containing DPC micelles. Monolayer penetration
      experiments and further MD simulations demonstrate that mutating hydrophobic
      residues to polar residues in the flanking loops reduces membrane penetration.
      This supports a "dual-recognition" model of binding, with specific GRP1-PH
      PI(3,4,5)P(3) interactions supplemented by interactions of loop regions with the
      lipid bilayer.

PMID- 21893294
TI  - Computational analysis of thoracic multidetector row HRCT for segmentation and
      quantification of small airway air trapping and emphysema in obstructive
      pulmonary disease.
AB  - RATIONALE AND OBJECTIVES: Obstructive pulmonary disease phenotypes are related to
      variable combinations of emphysema and small-airway disease, the latter
      manifested as air trapping (AT) on imaging. The investigators propose a method to
      extract AT information quantitatively from thoracic multi-detector row high
      resolution computed tomography (HRCT), validated by pulmonary function testing
      (PFT) correlation. MATERIALS AND METHODS: Seventeen patients with obstructive
      pulmonary disease who underwent HRCT and PFT within a 3-day interval were
      retrospectively identified. Thin-section volumetric HRCT in inspiration and
      expiration was registered and analyzed using custom-made software. Nonaerated
      regions of lung were segmented through exclusion of voxels > -50 Hounsfield units
      (HU); emphysematous areas were segmented as voxels < -950 HU on inspiratory
      images. Small-airway AT volume (ATV) was segmented as regions of lung voxels
      whose attenuation values increased by less than a specified change threshold (set
      from 5 to 300 HU in 25-HU increments) between inspiration and expiration.
      Inspiratory and expiratory total segmented lung volumes, emphysema volume (EV),
      and ATV for each threshold were subsequently calculated and correlated with PFT
      parameters. RESULTS: A strong positive correlation was obtained between total
      segmented lung volume in inspiration and total lung capacity (r = 0.83). A strong
      negative correlation (r = -0.80) was obtained between EV and the ratio between
      forced expiratory volume in 1 second and forced vital capacity. Stronger negative
      correlation with forced expiratory volume in 1 second/forced vital capacity (r = 
      0.85) was demonstrated when ATV (threshold, 50 HU) was added to EV, indicating
      improved quantification of total AT to predict obstructive disease severity. A
      moderately strong positive correlation between ATV and residual volume was
      observed, with a maximum r value of 0.72 (threshold, 25 HU), greater than that
      between EV and residual volume (r = 0.58). The benefit of ATV quantification was
      greater in a subgroup of patients with negligible emphysema compared to patients
      with moderate to severe emphysema. CONCLUSIONS: Small-airway AT segmentation in
      conjunction with emphysema segmentation through computer-assisted methodologies
      may provide better correlations with key PFT parameters, suggesting that the
      quantification of emphysema-related and small airway-related components of AT
      from thoracic HRCT has great potential to elucidate phenotypic differences in
      patients with chronic obstructive pulmonary disease.

PMID- 21893296
TI  - Breast tomosynthesis: state-of-the-art and review of the literature.

PMID- 21893295
TI  - The frequency and spectrum of thymus 2-[fluorine-18] fluoro-2-deoxy-D-glucose
      uptake patterns in hyperthyroidism patients.
AB  - RATIONALE AND OBJECTIVES: Thymic hyperplasia is associated with hyperthyroidism.
      Increased thymus 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) uptake in
      hyperthyroidism patients has been reported. The aim of this study was to analyze
      the FDG positron emission tomography (PET) thymus uptake spectrum in patients
      with active hyperthyroidism with correlation with serum hormones. MATERIALS AND
      METHODS: The prospective study included FDG PET scans from 65 hyperthyroidism
      patients and 30 subjects with euthyroid status as control group. The intensity of
      FDG uptake in thyroid and thymus regions was graded subjectively on a five-point
      scale and semi-quantitatively by measuring standard uptake value (SUV).
      Correlation coefficient between thymus SUV and serum thyroxine, triiodothyronine,
      thyrotropin, thyroid peroxidase antibodies (TPO Ab), thyrotropin receptor
      autoantibody (TR Ab), and thymulin were analyzed. RESULTS: Among 65
      hyperthyroidism patients, 30 (46.2%) and 39 (60%) patients showed thyroid and
      thymus FDG uptake, respectively. The frequency of thymus uptake FDG was high in
      patients younger than age 40 (28/31, 90.3%). The patterns of the thymic FDG
      uptake include inverted V or triangular, separated triangular, united
      nontriangular, unilateral right or left extension, and focal midline. Focal
      midline FDG uptake was the most common pattern (15/39, 38.5%). None of the
      control group showed thymus FDG uptake. The correlation coefficient between the
      FDG uptake SUV levels in thymus and serum hormones, thyrotropin, TPO Ab, TR Ab,
      and thymulin levels were all low (P > .05). CONCLUSIONS: In FDG PET scan, thymus
      activity was common in hyperthyroidism patients; this should not be misdiagnosed
      as a malignancy in patients exhibiting weight loss.

PMID- 21893297
TI  - Perfusion computed tomography evaluation of partial hepatic ischemia reperfusion
      in a rabbit model.
AB  - RATIONALE AND OBJECTIVES: An animal model of partial hepatic ischemia/reperfusion
      injury (I/R) has benefits for decision making and clinical management after liver
      transplantation or massive hepatic resection. The aim of this study was to
      evaluate the change in perfusion parameters after partial hepatic I/R in rabbits
      using multislice computed tomography perfusion imaging. MATERIALS AND METHODS:
      Thirty rabbits underwent 60 minutes of left hepatic lobar ischemia followed by
      0.5, 2, 6, 12, and 24 hours of reperfusion (six rabbits were used for each
      reperfusion interval). An additional six rabbits served as sham-operated
      controls. The perfusion indices of hepatic arterial perfusion, hepatic portal
      perfusion, total liver perfusion, and hepatic perfusion index were measured.
      Levels of serum aspartate transaminase and alanine transaminase and liver
      histopathology at different time points were also examined. RESULTS: Hepatic
      microvascular flow patterns showed heterogeneity in the 6-hour, 12-hour, and 24
      hour groups. Computed tomographic perfusion parameters were significantly
      different between infarcted liver tissue and viable liver tissue. In poorly
      enhancing tissues in the 6-hour, 12-hour, and 24-hour groups, hepatic portal
      perfusion and total liver perfusion were lower compared to the sham group, but
      hepatic arterial perfusion of poorly enhancing tissues significantly increased in
      the 6-hour group and then decreased slightly from 12 to 24 hours after
      reperfusion. The hepatic perfusion index was always higher compared to that of
      the sham group. Hepatic arterial perfusion, hepatic portal perfusion, total liver
      perfusion, and hepatic perfusion index in the noninfarcted areas decreased slowly
      from 6 to 24 hours after reperfusion. The levels of alanine transaminase and
      aspartate transaminase in the I/R groups significantly increased after
      reperfusion and were correlated with the computed tomographic perfusion indices
      of infarcted liver tissue. CONCLUSIONS: Computed tomographic perfusion can
      dynamically monitor the pathologic processes of liver I/R and reveal the
      underlying microvascular disorder, improving clinical management after liver
      surgery.

PMID- 21893298
TI  - Effects of radiofrequency ablation on normal lung tissue in a swine model.
AB  - RATIONALE AND OBJECTIVES: To determine the effect of radiofrequency (RF) ablation
      on normal lung tissue in an animal model. MATERIALS AND METHODS: RF ablation of
      lung tissue was performed on eight swine under computed tomographic control.
      Group A (n = 4) received peripheral ablation (subpleural needle placement) and
      group B (n = 4) received central ablation (hilar needle placement). RF ablation
      was applied via a single 4.5-gauge internally cooled electrode with a 2-cm tip
      for 12 minutes. The ablation was monitored with computed tomography at 3, 7, and
      12 minutes, and 10 minutes after ablation. After 3, 7, 40, and 60 days, computed
      tomography was performed, and the animals were sacrificed to examine the lung
      tissue both macroscopically and histopathologically. RESULTS: There were no
      deaths from RF ablation. In group A, coagulative necrosis was resorbed almost
      completely and transformed into a fibrotic scar after 60 days. No pneumothorax,
      pleural effusion, or lung abscess was observed. In group B, there was also a
      transformation of the necrosis into connective tissue. Neither the pulmonary
      vessels nor the bronchi of the hilum abutting the coagulative necrosis were
      damaged. After 60 days, no vascular thrombosis, bleeding, aneurysm, bronchial
      stenosis, or bronchopulmonary fistula was observed. CONCLUSION: RF ablation of
      lung tissue affects coagulation necrosis, causing scar transformation. There was
      no damage to either great vessels or bronchi. The application of RF ablation for
      tumors located in or near functional structures appears feasible without severe
      complications.

PMID- 21893299
TI  - Utilizing a PACS-integrated ultrasound-guided breast biopsy simulation exercise
      to reinforce the ACR practice guideline for ultrasound-guided percutaneous breast
      interventional procedures during radiology residency.
AB  - RATIONALE AND OBJECTIVES: A picture archiving and communication system (PACS)
      integrated ultrasound-guided (USG) breast intervention simulation exercise was
      designed for radiology residency education. The purpose of this study was to
      describe the initial experience and determine if resident understanding of the
      American College of Radiology (ACR) practice guideline for the performance of USG
      percutaneous breast interventional procedures and procedural confidence is
      improved with the implementation of this simulation exercise. MATERIALS AND
      METHODS: Radiology residents (n = 11) volunteered to perform percutaneous USG
      cyst aspiration, 14-gauge automated core biopsy, and 10-gauge vacuum core biopsy
      on turkey breast phantoms, with an emphasis on capturing ultrasound images
      demonstrating appropriate documentation of the procedure and image annotation
      according to the ACR practice guideline for USG percutaneous interventions. The
      images were transmitted to the PACS for subsequent attending radiologist review.
      Survey responses regarding procedural confidence and knowledge of the ACR
      practice guideline were compared between residents with and without the simulator
      experience. RESULTS: Residents with simulation exercise experience showed
      statistically significant increases in confidence performing USG core biopsies,
      operating biopsy devices and ultrasound equipment, and knowledge of appropriate
      needle positioning and image annotation and documentation according to the ACR
      practice guideline. The increased confidence seen in performing USG cyst
      aspiration barely missed statistical significance (P = .056), likely because of
      residents' baseline familiarity with the procedure. CONCLUSIONS: A PACS
      integrated USG breast intervention simulation exercise increases residents'
      procedural confidence and understanding of the ACR practice guideline for the
      performance of USG percutaneous breast interventional procedures.

PMID- 21893300
TI  - Puberty.

PMID- 21893301
TI  - Are we monitoring what we think we are monitoring?

PMID- 21893302
TI  - American Society for Pain Management Nursing guidelines on monitoring for opioid
      induced sedation and respiratory depression.
AB  - As the complexity of analgesic therapies increases, priorities of care must be
      established to balance aggressive pain management with measures to prevent or
      minimize adverse events and to ensure high quality and safe care. Opioid
      analgesia remains the primary pharmacologic intervention for managing pain in
      hospitalized patients. Unintended advancing sedation and respiratory depression
      are two of the most serious opioid-related adverse events. Multiple factors,
      including opioid dosage, route of administration, duration of therapy, patient
      specific factors, and desired goals of therapy, can influence the occurrence of
      these adverse events. Furthermore, there is an urgent need to educate all members
      of the health care team about the dangers and potential attributes of
      administration of sedating medications concomitant with opioid analgesia and the
      importance of initiating rational multimodal analgesic plans to help avoid
      adverse events. Nurses play an important role in: 1) identifying patients at risk
      for unintended advancing sedation and respiratory depression from opioid therapy;
      2) implementing plans of care to assess and monitor patients; and 3) intervening
      to prevent the worsening of adverse events. Despite the frequency of opioid
      induced sedation, there are no universally accepted guidelines to direct
      effective and safe assessment and monitoring practices for patients receiving
      opioid analgesia. Moreover, there is a paucity of information and no consensus
      about the benefits of technology-supported monitoring, such as pulse oximetry
      (measuring oxygen saturation) and capnography (measuring end-tidal carbon
      dioxide), in hospitalized patients receiving opioids for pain therapy. To date,
      there have not been any randomized clinical trials to establish the value of
      technologic monitoring in preventing adverse respiratory events. Additionally,
      the use of technology-supported monitoring is costly, with far-reaching
      implications for hospital and nursing practices. As a result, there are
      considerable variations in screening for risk and monitoring practices. All of
      these factors prompted the American Society for Pain Management Nursing to
      approve the formation of an expert consensus panel to examine the scientific
      basis and state of practice for assessment and monitoring practices for adult
      hospitalized patients receiving opioid analgesics for pain control and to propose
      recommendations for patient care, education, and systems-level changes that
      promote quality care and patient safety.

PMID- 21893303
TI  - Improved practices for safe administration of intravenous bolus morphine in a
      pediatric setting.
AB  - Postoperative pain control is a clinical imperative, for which morphine is a
      preferred opioid. However, interpatient variability and drug accumulation with
      repeated doses, as well as medication errors, may result in respiratory arrest
      with this medication. Early detection of respiratory depression is essential for
      safe use of morphine, following both initial and repeated doses. A
      multidisciplinary team contributed to development of an intravenous (IV) bolus
      morphine monitoring guideline that reflects current knowledge of morphine
      pharmacokinetics. Monitoring over a 22-week period in a postsurgical unit was
      then assessed via record review. A total of 270 postsurgical patients received a
      first dose of IV bolus morphine, with 784 subsequent doses also administered.
      Complete monitoring (heart rate, respiratory rate, blood pressure, sedation
      score, oxygen saturation, and pain score) after the morphine bolus was documented
      at baseline and 10 and 20 minutes for 34%, 30%, and 23%, respectively, of the
      patients; partial monitoring (respiratory rate and oxygen saturation) was
      documented for an additional 22%, 15%, and 9% of patients; 43% of subsequent
      morphine doses were followed with complete monitoring, and an additional 30% with
      at least partial monitoring. Adherence to the monitoring procedure fluctuated
      over the study period with no consistent upward or downward trend. A small number
      of children exhibited a reduced respiratory rate potentially indicating
      respiratory depression, but no child required antidote or respiratory support.
      Despite suboptimal guideline adherence, potential signs of respiratory depression
      were detected that might otherwise have gone unnoticed. This validates the
      improved guideline and suggests that some incidents may have remained undetected.
      Front-line staff must be involved to optimize change, champion the initiative,
      and promote patient safety.

PMID- 21893304
TI  - Barriers to pediatric pain management: a nursing perspective.
AB  - This study describes strategies used by the Joint Clinical Practice Council of
      Children's Hospital of Wisconsin to identify barriers perceived as interfering
      with nurses' (RNs) ability to provide optimal pain management. A survey was used
      to ascertain how nurses described optimal pain management and how much nurses
      perceived potential barriers as interfering with their ability to provide that
      level of care. The survey, "Barriers to Optimal Pain management" (adapted from
      Van Hulle Vincent & Denyes, 2004), was distributed to all RNs working in all
      patient care settings. Two hundred seventy-two surveys were returned. The five
      most significant barriers identified were insufficient physician (MD) orders,
      insufficient MD orders before procedures, insufficient time to premedicate
      patients before procedures, the perception of a low priority given to pain
      management by medical staff, and parents' reluctance to have patients receive
      pain medication. Additional barriers were identified through narrative comments.
      Information regarding the impact of the Acute Pain Service on patient care, RNs'
      ability to overcome barriers, and RNs' perception of current pain management
      practices is included, as are several specific interventions aimed at improving
      or ultimately eliminating identified barriers.

PMID- 21893305
TI  - Critical care nurses' experiences: "a good relationship with the patient is a
      prerequisite for successful pain relief management".
AB  - There is a lack of studies describing how critical care nurses experience
      assessing and treating pain in patients receiving postoperative care in an
      intensive care unit (ICU). The aim of this study was to describe those
      experiences. Qualitative personal interviews with six critical care nurses in an
      ICU in northern Sweden were conducted during 2009. The interview texts were
      subjected to qualitative content analysis, which resulted in the formulation of
      one theme and four categories. It was important to be able to recognize signs of
      pain in patients unable to communicate verbally. In older patients, anxiety could
      be interpreted as an indication of pain. Pain was primarily assessed by means of
      a visual analog scale. Being unable to treat pain successfully was experienced as
      failing in one's work. Pharmacologic treatment was always the first choice for
      relief. The environment was experienced as a hindrance to optimal nursing care,
      because all postoperative patients shared a room with only curtains between them.
      The work of assessing and treating pain in patients receiving postoperative care
      is an important and frequent task for critical care nurses, and knowledge in the
      field is essential if the patients are to receive optimal nursing care and
      treatment. Patients cared for in an ICU might benefit from nonpharmacologic
      treatment. Being without pain after surgery implies increased well-being and
      shorter hospitalization for the patient.

PMID- 21893306
TI  - Hispanic older adults' osteoarthritis pain communication.
AB  - Better understanding of how Hispanic older adults describe their chronic pain
      might suggest ways to support Hispanic older adults to talk about important pain
      information with their practitioner. The study aim was to describe how Hispanic
      older adults communicate pain information, including the amount of pain
      information and communication processes employed. A secondary analysis with a
      descriptive design was used. The data were from a larger primary study that
      tested the effect of practitioner pain question phrasing on the amount of pain
      information described by older adults with osteoarthritis pain. The sample for
      this secondary analysis was composed of the 24 Hispanic older adults with chronic
      osteoarthritis pain. In the primary study older adults watched and orally
      responded to a videotape of a practitioner asking about their pain. Pain content
      from the patient responses was content analyzed by two independent raters.
      Communication processes were also content analyzed by two independent raters
      using a priori criteria from communication accommodation theory (clarity, syntax,
      complexity, explicitness, and staying on topic). Participants described a mean of
      5.5 (SD 3.39) items of pain information. The majority stayed on topic, and one
      half spoke clearly and explicitly. Hispanic older adults with osteoarthritis pain
      concisely describe clinically important pain information when given the
      opportunity to do so.

PMID- 21893307
TI  - Risk factors for opioid-induced excessive respiratory depression.
AB  - Opioid use has increased significantly over the past ten years and so has the
      incidence of reportable adverse events, such as respiratory depression and/or
      arrest. It is important for nurses to understand and know how to assess patients
      for risk factors for respiratory depression secondary to opioid therapy. This
      paper presents the pharmacodynamics of opioids, the risk factors for excessive
      respiratory depression, recommendations for identifying patients at high risk,
      and interventions to prevent adverse effects. After reading this paper, nurses
      will have the knowledge to provide safe administration of opioid medications for
      the management of acute pain.

PMID- 21893308
TI  - Common iliac vein stenosis: a risk factor for oral contraceptive-induced deep
      vein thrombosis.
AB  - OBJECTIVE: The objective of the study was to determine whether women with
      significant left common iliac vein stenosis who also use combined oral
      contraceptives (COCs) have a combined likelihood of deep vein thrombosis (DVT)
      greater than each independent risk. STUDY DESIGN: This was a case-control study
      comparing 35 women with DVT against 35 age-matched controls. Common iliac vein
      diameters were measured from computed tomography and magnetic resonance imaging.
      Logistic regression modeling was used with adjustment for risk factors. RESULTS:
      DVT was associated with COC use (P = .022) and with increasing degrees of common
      iliac vein stenosis (P = .004). Compared with women without venous stenosis or
      COC use, the odds of DVT in women with a 70% venous stenosis who also use COCs
      was associated with a 17-fold increase (P = .01). CONCLUSION: Venous stenosis and
      COC use are independent risk factors for DVT. Women concurrently exposed to both
      have a multiplicative effect resulting in an increased risk of DVT. We recommend
      further studies to investigate this effect and its potential clinical
      implications.

PMID- 21893309
TI  - Passive immunization: the forgotten arm of immunologically based strategies for
      disease containment.
AB  - Passive immunization provides temporary protection in a naive subject who has
      been exposed to an infectious pathogen when vaccination is unavailable or has not
      been given before exposure. Despite the recent attention that has been given to
      adult-directed vaccines, antibody-based therapeutic strategies have received
      little discussion yet remain an important part of infectious disease containment.
      This review examines some of the more common clinical situations in which an
      obstetrician-gynecologist may need to have expertise related to passive
      immunization. Potential future uses for this modality are presented.

PMID- 21893310
TI  - First-trimester uterine scar assessment by transvaginal ultrasound.
AB  - OBJECTIVE: The objective of the study was to describe the assessment of lower
      segment uterine scar (LSCS) by transvaginal ultrasound (TVUS) during a first
      trimester scan. STUDY DESIGN: Patients with a history of LSCS were prospectively
      enrolled over a 6 month period. Four groups were defined: type 1A, thin scar
      within cervicoisthmic canal (CIC); type 1B, thin above the internal os (IO); type
      2A, dehiscent within the CIC; type 2B, dehiscent above the IO. Accuracy of first
      trimester TVUS was investigated by blind testing a panel of 14 operators over a
      web-based dataset. RESULTS: The scar was visualized in 122 of 123 patients
      enrolled. Types 1A, 1B, 2A, and 2B occurred in 49.2%, 3.3%, 38.3%, and 9.2%,
      respectively. When blind tested, fetal medicine specialists achieved a median
      sensitivity of 82% and specificity of 100% for the detection of a scar. These
      were 83% and 87% for nonspecialists. CONCLUSION: First-trimester uterine scar
      assessment may become a valuable tool in early recognition of patients at risk of
      subsequent perinatal complications.

PMID- 21893311
TI  - Is ovarian volume estimation reliable when compared with true volume?
AB  - OBJECTIVE: We aimed to evaluate the agreement of 2-dimensional (2D) and 3
      dimensional (3D) ultrasonography (USG) with true ovarian volume (OV), as
      calculated precisely after oophorectomy. STUDY DESIGN: A total of 46 ovaries from
      30 patients were prospectively enrolled. Preoperatively, all ovaries were
      assessed by 2D and 3D USG for volume estimation and results were compared with
      true OV that was calculated with Archimedes' principles following oophorectomy.
      RESULTS: The correlation coefficients of 2D and 3D USG with true OV were similar
      (0.65 vs 0.67, respectively). The mean bias (upper and lower limits of agreement)
      between 2D and true OV was 1.41 (-3.84 to 6.66) mL. The respective figure for 3D
      and true OV were 0.33 (-4.71 to 5.37) mL. While estimation by 2D USG brought 18%
      larger, 3D USG revealed 11% smaller values than the true OV. CONCLUSION: Three
      dimensional OV estimation might present improvement in means of lower mean bias
      than 2D USG.

PMID- 21893312
TI  - Ergonomic factors on task performance in laparoscopic surgery training.
AB  - This paper evaluates the effect of ergonomic factors on task performance and
      trainee posture during laparoscopic surgery training. Twenty subjects without
      laparoscopic experience were allotted into 2 groups. Group 1 was trained under
      the optimal ergonomic simulation setting according to current ergonomic
      guidelines (Condition A). Group 2 was trained under non-optimal ergonomic
      simulation setting that can often be observed during training in a skills lab
      (Condition B). Posture analysis showed that the subjects held a much more neutral
      posture under Condition A than under Condition B (p<0.001). The subjects had less
      joint excursion and experienced less discomfort in their neck, shoulders, and
      arms under Condition A. Significant difference in task performance between
      Conditions A and B (p<0.05) was found. This study shows that the optimal
      ergonomic simulation setting leads to better task performance. In addition, no
      significant differences of task performance, for Groups 1 and 2 using the same
      test setting were found. However, better performance was observed for Group 1. It
      can be concluded that the optimal and non-optimal training setting have different
      learning effects on trainees' skill learning.

PMID- 21893313
TI  - [Add that...].

PMID- 21893314
TI  - Different involutionary changes in bone mineral density with age in three
      skeletal sites in healthy Polish women.
AB  - The aim of the study was to estimate the differences in bone mineral density
      (BMD) at three skeletal sites, with regard to age and menopausal status. The
      study was conducted between 2001 and 2006 in the Polish city of Wroclaw and the
      sample was comprised of 440 healthy female inhabitants aged 40-88years. The
      measurements of bone mineral density were taken at three sites: femoral neck,
      Ward's triangle and trochanter major. Two bone mineral density characteristics
      were used in further analysis: absolute measure of bone mineral density (BMD)
      expressed in g/(100mm)(2), and % of BMD of the peak value calculated for young
      adults (20-45, USA reference population). Pre- and postmenopausal status was
      defined according to occurrence of menstruation within the last 60days. The
      changes in bone mineral density with age showed significantly different patterns
      in different skeletal sites. While the decrease in bone mineral density in the
      femoral neck and Ward's triangle were parallel and gradual, the changes in
      trochanter major were very small and between the age groups 51-55 and 71-75,
      nearly unnoticeable. A comparison between pre- and postmenopausal women aged 46
      55, showed a significant effect of menopausal status. The average bone mineral
      densities in the three skeletal sites were higher in premenopausal than in
      postmenopausal women. The highest value of bone mineral density was found in the
      femoral neck, significantly lower in Ward's triangle, and a little lower (non
      significantly) in the trochanter major than in the Ward's triangle.
      Postmenopausal women had a little higher BMD value in the trochanter major than
      in the Ward's triangle site.

PMID- 21893315
TI  - Fall related injuries: a retrospective medical review study in North India.
AB  - INTRODUCTION: Falls have been identified as a leading cause of injury-related
      morbidity and mortality in India. However, very little is known about the context
      and characteristics of such falls. The aim of this study was to describe the
      context and characteristics of fall related injuries in patients admitted to
      hospital for fall injury. METHODS: Medical records of patients presenting at the
      Emergency Department of the Nehru Hospital, Chandigarh, India between March 2008
      and February 2009, were reviewed by trained investigators. All injury cases were
      identified and fall related injury cases were assigned an ICD 10, Chapter XX,
      External causes of morbidity and mortality code. A review of medical records was
      conducted to determine the context, nature and site of injury associated with a
      fall event. RESULTS: Ten percent (7049) of hospital emergency presentations were
      due to injuries, and falls were the second leading cause (20%, 1407). Seventy-six
      percent of the fall related presentations were in males. More than one third
      (36%) of the fall related presentations occurred in those aged 0-14 years old.
      Falls from building or structures (35%, 499) were the leading cause for all ages
      except for those older than 60 years, where same level falls due to slipping,
      tripping and stumbling (40%, 57) were predominant. Half of all the falls resulted
      in head injury. Nearly 10% of patients presenting for fall related injury died.
      CONCLUSION: Fall related injuries are an important contributor to hospital
      emergency presentations, particularly falls from buildings in children, and slips
      and trips in older people. Given the high proportion of falls that resulted in
      head injury and death, there is a significant need to develop appropriate
      interventions to prevent such falls.

PMID- 21893316
TI  - Effects of ramp negotiation, paving type and shoe sole geometry on toe clearance
      in young adults.
AB  - Trips are a major cause of falls and result from involuntary contact of the foot
      with the ground during the swing phase of gait. Adequate toe clearance during
      swing is therefore crucial for safe locomotion. To date, little is known about
      the effects of environmental factors and footwear on toe clearance. This study
      reports on modulation of toe clearance and toe clearance variability in response
      to changes in ground inclination, paving type, and shoe sole geometry. Toe
      clearance and toe clearance variability for ten healthy young adults were
      calculated two-fold: a) for the commonly-used position on the foremost part of
      the sole of the shoe and b) for the lowest of a total of 7 sole positions,
      located between the metatarsals and the toe tip across the entire width of the
      sole. Utilizing a full-factorial design we found that toe clearance was affected
      by ground inclination, paving type, and sole geometry regardless of the
      computational method used (with p-values<0.01) but the use of the foremost part
      of the sole for toe clearance calculation results is an overestimation of this
      value. Our findings highlight the importance of considering footwear and
      environmental factors when assessing the risk of tripping. Future work needs to
      investigate to which extent the same factors affect toe clearance in more
      vulnerable parts of the population.

PMID- 21893317
TI  - Reequilibration time of superficially porous silica based columns in gradient
      elution reversed phase liquid chromatography.
AB  - Between repetitive analyses using gradient elution liquid chromatography the
      column must be reequilibrated to the initial conditions, extending run times. We
      studied the reequilibration time of three superficially porous silica columns
      compared to one fully porous silica column on a chromatograph with a reduced
      flush-out volume. Post-gradient acetone injections made at the interface of the
      pure organic-highly aqueous phase show anomalous, pressure-related band focusing,
      and increased retention compared to injections on either side of the interface.
      These anomalies are explained by applying the Buckley-Leverett theory of oil
      displacement in sands to column reequilibration. Reequilibration was shown to
      occur quickly, with less than three column volumes of conditioning solvent, and
      depends on the reproducibility as required by the application. Offline LC-GC was
      used to quantitate the percent acetonitrile eluting from each column post
      gradient. After an initial, large expulsion of acetonitrile, a steady small
      amount (~0.03%) of acetonitrile is detected long after the column is considered
      equilibrated. The limiting variable with column equilibration is not the
      desorption of organic modifier from the stationary phase, but rather the pressure
      required to force the aqueous phase into the pores.

PMID- 21893318
TI  - Determination of organic acid impurities in lactic acid obtained by fermentation
      of sugarcane juice.
AB  - Lactic acid produced by fermentation process mostly contains a number of
      aliphatic carboxylic acids as impurities. In this work, carboxylic acid
      impurities in lactic acid samples from a number of sources were determined at ppm
      levels. A simple HPLC method was developed that utilized a new generation polar
      embedded reverse phase, 20mM phosphate buffer at pH 2.20 (+/-0.05) and UV
      detection at 210 nm. The method enabled quantitative analysis of the above acids
      in lactic acid matrix. The experimental conditions for column temperature, mobile
      phase pH and flow rate were optimized. A detailed validation of the method was
      performed for linearity, precision, accuracy, selectivity, limit of detection
      (LOD), limit of quantitation (LOQ), ruggedness and repeatability and
      reproducibility (R&R).

PMID- 21893319
TI  - Quantitative trace analysis of eight chloramphenicol isomers in urine by chiral
      liquid chromatography coupled to tandem mass spectrometry.
AB  - Chloramphenicol is a broad-spectrum antibiotic with, apart from its human
      medicinal use, veterinary abuse in all major food-producing animals.
      Chloramphenicol occurs in four stereoisomers (all para-nitro substituted) and
      furthermore four meta-nitro analogs of chloramphenicol exist. In this paper these
      are referred to as eight chloramphenicol isomers. According to EU regulations an
      analytical method should be able to discriminate the analyte from interfering
      substances that might be present in the sample, including isomers. For the first
      time a quantitative method for the analysis of trace levels of eight
      chloramphenicol isomers in urine by chiral liquid chromatography in combination
      with tandem mass spectrometric detection is reported. The separation of the
      isomers on the analytical column, the clean-up of urine and the selectivity of
      the monitored product ions turned out to be critical parameters. To obtain
      reproducible retention isocratic elution on a chiral AGP column was applied. For
      urine samples matrix compounds present in the final extract caused decreased
      retention of the isomers on the chiral stationary phase and a lack of
      chromatographic resolution. Therefore an extended clean-up procedure that
      combines solid phase extraction and liquid-liquid extraction had to be developed.
      The final method was fully validated and showed satisfactory performance for all
      isomers with decision limits (CCalpha) ranging from 0.005 to 0.03 MUg L(-1) and
      within-laboratory reproducibility of all isomers below 20% at the minimum
      required performance limit level of 0.3 MUg L(-1).

PMID- 21893320
TI  - Kinetic plot based comparison of the efficiency and peak capacity of high
      performance liquid chromatography columns: theoretical background and selected
      examples.
AB  - The present contribution reviews the foundations of the kinetic-plot method for
      the direct comparison of the kinetic performance of different chromatographic
      support and operating modes. The method directly uses experimental data collected
      for a specific sample and operating condition of one's interest, and is
      applicable both under isocratic- and gradient-elution conditions. Experimental
      proof is provided for the strong relation between the kinetic performance of a
      given support under isocratic and gradient conditions: a material offering
      superior kinetic performances under isocratic conditions will remain superior
      under gradient conditions and vice versa provided the comparison occurs under
      unbiased conditions. In addition, a review is made of the recent literature using
      the kinetic-plot method to compare and assess the kinetic performance of high
      performance HPLC columns and their operation mode.

PMID- 21893321
TI  - Microfluidic circuit analysis II: implications of ion conservation for
      microchannels connected in series.
AB  - A mathematical framework for analysing electrokinetic flow in microchannel
      networks is outlined. The model is based on conservation of volume and total
      charge at network junctions, but in contrast to earlier theories also
      incorporates conservation of ion charge there. The model is applied to mixed
      pressure-driven/electro-osmotic flows of binary electrolytes through homogeneous
      microchannels as well as a 4:1:4 contraction-expansion series network. Under
      conditions of specified volumetric flow rate and ion currents, non-linear steady
      state phenomena may arise: when the direction of the net co-ion flux is opposite
      to the direction of the net volumetric flow, two different fully developed,
      steady-state flow solutions may be obtained. Model predictions are compared with
      two-dimensional computational fluid dynamics (CFD) simulations. For systems where
      two steady states are realisable, the ultimate steady behaviour is shown to
      depend in part upon the initial state of the system.

PMID- 21893322
TI  - Prevalence of dementia and mild cognitive impairment in the elderly living in
      nursing and veteran care homes in Xi'an, China.
AB  - DESIGN: Cross-sectional surveys using cluster sampling. OBJECTIVES: To explore
      the prevalence of dementia and mild cognitive impairment (MCI) in several nursing
      homes (NHs) and veteran care homes (VCHs) in Xi'an City and their various risk
      factors. PARTICIPANTS AND MEASUREMENTS: 264 native elderly people from four NHs
      and two VCHs were examined with several screening tests for dementia: Mini Mental
      State Examination (MMSE), Activities of Daily Living (ADL) and Hasegawa Dementia
      Scale (HDS). Diagnosis of dementia and MCI were made according to DSM-III-R and
      Petersen's criteria. Socio-demographic characteristics and past history were also
      collected. RESULTS: Dementia prevalence was 36.7% in those living in NHs and
      VCHs, much higher than that of normal population and the prevalence of MCI was
      13.3% which was the same as in normal population. Dementia was associated with
      old age, female, low education level and living in NHs. Men had significantly
      higher prevalence odds for MCI. Very old age, living in NHs and severe ADL
      impairment were correlated with higher prevalence odds for dementia and MCI.
      CONCLUSION: The prevalence of dementia in the elderly living in groups in Xi'an
      was high, especially living in NHs.

PMID- 21893323
TI  - Idiopathic Parkinson's syndrome. Preface.

PMID- 21893324
TI  - Caucasicosides E-M, furostanol glycosides from Helleborus caucasicus.
AB  - Nine furostanol glycosides, namely caucasicosides E-M, were isolated from the
      MeOH extract of the leaves of Helleborus caucasicus, along with 11 known
      compounds including nine furostanol glycosides, a bufadienolide and an
      ecdysteroid. Their structures were established by the extensive use of 1D and 2D
      NMR experiments along with ESIMS(n) analyses. The steroidal composition of leaves
      of H. caucasicus shows as particular feature the occurrence of steroidal
      compounds belonging to the 5beta series, unusual for Helleborus species, and in
      particular, caucasicosides F-H are based on a 5beta-polyhydroxylated steroidal
      aglycon never reported before.

PMID- 21893325
TI  - Terpenoids and phenethyl glucosides from Hyssopus cuspidatus (Labiatae).
AB  - Monoterpenoids (3 and 4), sesquiterpenoid (2), diterpenoid (1) and four phenethyl
      glucosides (5-8), together with fourteen known compounds, were isolated from the
      whole herb of Hyssopus cuspidatus. Their structures were determined by
      spectroscopic means. The abietane-type diterpenoids (1, 9, 10), rosmarinic acid
      (15) and salvigenin (17) inhibited leukotriene (LT) C(4) secretion from primary
      alveolar cells of Wistar rats.

PMID- 21893326
TI  - Pitfalls in avoiding operation for autoimmune pancreatitis.
AB  - BACKGROUND: Despite improved clinical characterization, autoimmune pancreatitis
      is often still diagnosed only after a major operative procedure. This study seeks
      to elucidate the circumstances that contribute to an inaccurate preoperative
      diagnosis. METHODS: Two independent reviewers identified retrospectively an
      institutional cohort of 68 patients with adequate clinical data to support the
      diagnosis of autoimmune pancreatitis. Further data regarding presentation,
      diagnostic studies, and clinical course was abstracted from medical records.
      Comparative analyses were performed between those patients who underwent major
      operative procedures and those who did not. RESULTS: Fifty-three patients
      underwent operative intervention as their initial treatment. Compared to the 15
      patients avoiding operation, these patients were less likely to have diffuse
      pancreatic enlargement identified on pretreatment imaging (8% vs 80%) or to have
      pretreatment serum IgG4 level evaluations (11% vs 100%). Among the 21 patients in
      whom IgG4 levels were first checked postoperatively, only 12 had increases of at
      least twice the upper limit of normal. Pretreatment fine needle aspirates were
      interpreted incorrectly as definite or suspicious for adenocarcinoma in 12
      patients, of whom 10 underwent operation. Clinically important postoperative
      disease recurrence was suspected or proven in 13 patients. CONCLUSION: Pitfalls
      leading to major pancreatic resections in autoimmune pancreatitis include
      unnecessarily high thresholds for initiating serum IgG4 evaluation, false
      positive cytologic evaluations for malignancy, and failure to recognize non
      classic initial presentations, or recurrence of disease. Better diagnostic
      strategies are needed, but awareness of these specific findings should help to
      decrease the number of patients undergoing operation for unrecognized autoimmune
      pancreatitis.

PMID- 21893327
TI  - Differences in metabolic urinary abnormalities in stone forming and nonstone
      forming patients with primary hyperparathyroidism.
AB  - BACKGROUND: Hyperparathyroidism is associated with hypercalciuria and
      nephrolithiasis. Urine calcium excretion decreases after parathyroidectomy, but
      whether there is a differential decrease between stone and nonstone formers
      remains controversial. We evaluated differences between stone formers and non
      stone formers in serum and urinary parameters before and after parathyroidectomy.
      METHODS: 90 patients, 40 with and 50 without a history of nephrolithiasis
      underwent parathyroidectomy for hyperparathyroidism; 24-hour urine samples were
      collected before and after parathyroidectomy. Overall, 92% of patients provided
      samples before parathyroidectomy and 63% after parathyroidectomy. Preoperative,
      postoperative and changes in urinary parameters were evaluated. RESULTS:
      Preoperative hypercalciuria was present in ~65% in both groups (P = .68).
      Parathyroidectomy decreased serum levels of calcium, parathyroid hormone, and
      urinary calcium, but there were no differences between stone formers and nonstone
      formers. Stone formers were 12-fold (P = .001) more likely to resolve an increase
      in supersaturation of calcium oxalate (SSCaOx), and after adjustment for age,
      sex, and BMI were 46-fold (P = .002) more likely to resolve an increase in
      SSCaOx. After parathyroidectomy, the rate of stone recurrence was 23% and male
      sex (aOR 20, P = .032) and increasing BMI (aOR 1.23, P = .038) were the only
      independent predictors of stone recurrence after adjusting for age. No other
      factor evaluated preoperatively, postoperatively, or the change after
      parathyroidectomy differentiated stone and nonstone formers or predicted stone
      recurrence. CONCLUSION: Metabolic evaluation did not differentiate stone formers
      from nonstone formers reliably. Stone formers were more likely to resolve an
      increase in SSCaOx after parathyroidectomy. Male sex and increasing BMI were
      independently associated with stone recurrence after parathyroidectomy.

PMID- 21893328
TI  - The angiogenic factor Del1 prevents apoptosis of endothelial cells through
      integrin binding.
AB  - BACKGROUND: Del1 is a secreted protein that is expressed in the endothelium
      during development and can stimulate angiogenesis through integrin binding and
      signaling. We were interested in the specific effects of del1 on endothelial cell
      biology to gain insight into its biologic role during angiogenesis. METHODS:
      Primary endothelial cells were treated with a variety of inducers of apoptosis
      and anoikis followed by assays for numbers of apoptotic cells, and harvest of
      total protein for immunoblot analysis. RESULTS: Del1 prevented endothelial cell
      apoptosis in response to TNFalpha/IFNgamma, etoposide, and anoikis, but had no
      effect on proliferation. The anti-apoptotic effect was mediated specifically
      through binding of integrin alphavbeta3 by the RGD motif. FAK/ERK and Akt
      signaling were both necessary to mediate the anti-apoptotic effect of Del1 with
      the exception of anoikis, which required only Akt activation. CONCLUSION: Del1
      has been previously shown to promote vascular smooth muscle cell adhesion,
      migration, and proliferation. We demonstrate here that Del1 prevented apoptosis
      of endothelial cells in cell culture through integrin binding without any effect
      on proliferation.

PMID- 21893329
TI  - Determination of acoustic impedances of multi matching layers for narrowband
      ultrasonic airborne transducers at frequencies <2.5 MHz - Application of a
      genetic algorithm.
AB  - The effective ultrasonic energy radiation into the air of piezoelectric
      transducers requires using multilayer matching systems with accurately selected
      acoustic impedances and the thickness of particular layers. One major problem of
      ultrasonic transducers, radiating acoustic energy into air, is to find the proper
      acoustic impedances of one or more matching layers. This work aims at developing
      an original solution to the acoustic impedance mismatch between transducer and
      air. If the acoustic impedance defences between transducer and air be more, then
      finding best matching layer(s) is harder. Therefore we consider PZT (lead
      zirconate titanate piezo electric) transducer and air that has huge acoustic
      impedance deference. The vibration source energy (PZT), which is used to generate
      the incident wave, consumes a part of the mechanical energy and converts it to an
      electrical one in theoretical calculation. After calculating matching layers, we
      consider the energy source as layer to design a transducer. However, this part of
      the mechanical energy will be neglected during the mathematical work. This
      approximation is correct only if the transducer is open-circuit. Since the
      possibilities of choosing material with required acoustic impedance are limited
      (the counted values cannot always be realized and applied in practice) it is
      necessary to correct the differences between theoretical values and the
      possibilities of practical application of given acoustic impedances. Such a
      correction can be done by manipulating other parameters of matching layers (e.g.
      by changing their thickness). The efficiency of the energy transmission from the
      piezoceramic transducer through different layers with different thickness and
      different attenuation enabling a compensation of non-ideal real values by
      changing their thickness was computer analyzed (base on genetic algorithm).
      Firstly, three theoretical solutions were investigated. Namely, Chebyshev,
      Desilets and Souquet theories. However, the obtained acoustic impedances do not
      necessarily correspond to a nowadays available material. Consequently, the values
      of the acoustic impedances are switched to the nearest values in a large material
      database. The switched values of the acoustic impedances do not generally give
      efficient transmission coefficients. Therefore, we proposed, in a second step,
      the use of a genetic algorithm (GA) to select the best acoustic impedances for
      matching layers from the material database for a narrow band ultrasonic
      transducer that work at frequency below the 2.5MHz by considering attenuation.
      However this bank is rich, the results get better. So the accuracy of the propose
      method increase by using a lot of materials with exact data for acoustic
      impedance and their attenuation, especially in high frequency. This yields highly
      more efficient transmission coefficient. In fact by using increasing number of
      layer we can increase our chance to find the best sets of materials with valuable
      both in acoustic impedance and low attenuation. Precisely, the transmission
      coefficient is almost equal to unity for the all studied cases. Finally the
      effect of thickness on transmission coefficient is investigated for different
      layers. The results showed that the transmission coefficient for air media is a
      function of thickness and sensitive to it even for small variation in thickness.
      In fact, the sensitivity increases when the differences of acoustic impedances to
      be high (difference between PZT and air).

PMID- 21893330
TI  - Climate change: links to global expansion of harmful cyanobacteria.
AB  - Cyanobacteria are the Earth's oldest (~3.5 bya) oxygen evolving organisms, and
      they have had major impacts on shaping our modern-day biosphere. Conversely,
      biospheric environmental perturbations, including nutrient enrichment and
      climatic changes (e.g. global warming, hydrologic changes, increased frequencies
      and intensities of tropical cyclones, more intense and persistent droughts),
      strongly affect cyanobacterial growth and bloom potentials in freshwater and
      marine ecosystems. We examined human and climatic controls on harmful (toxic,
      hypoxia-generating, food web disrupting) bloom-forming cyanobacteria (CyanoHABs)
      along the freshwater to marine continuum. These changes may act synergistically
      to promote cyanobacterial dominance and persistence. This synergy is a formidable
      challenge to water quality, water supply and fisheries managers, because bloom
      potentials and controls may be altered in response to contemporaneous changes in
      thermal and hydrologic regimes. In inland waters, hydrologic modifications,
      including enhanced vertical mixing and, if water supplies permit, increased
      flushing (reducing residence time) will likely be needed in systems where
      nutrient input reductions are neither feasible nor possible. Successful control
      of CyanoHABs by grazers is unlikely except in specific cases. Overall, stricter
      nutrient management will likely be the most feasible and practical approach to
      long-term CyanoHAB control in a warmer, stormier and more extreme world.

PMID- 21893331
TI  - Concentrations and possible sources of polychlorinated biphenyls in the surface
      water of the Yangtze River Delta, China.
AB  - In this study, polychlorinated biphenyls (PCBs) pollution in the surface water of
      the Yangtze River Delta (YRD) was investigated. A total of 26 samples were
      collected from water bodies in three cities within the YRD during the dry season
      from October to November of 2009. The total PCBs (dissolved plus particulate)
      ranged from 1.23 to 16.6 ng L(-1) and were dominated by tri-, tetra-, and penta
      chlorinated biphenyls. The mean PCBs in the Beijing-Hangzhou Grand Canal and the
      Yangtze River were 8.84 and 3.36 ng L(-1), respectively. A t-test showed that
      there were no significant differences in the concentration of samples from the
      metropolitan area and the development zone. According to the Chinese national
      environmental quality standards for surface water (GB 3838-2002), the
      concentrations of PCBs observed in this study do not pose a hazard to aquatic or
      human health. Overall, this study described the PCB concentration and homolog
      distribution patterns in one of the most rapidly developing areas in China, and
      the results can be used as reference levels for future PCB monitoring programs.

PMID- 21893332
TI  - Kinetics and mechanism of propachlor reductive transformation through
      nucleophilic substitution by dithionite.
AB  - Chloroacetanilide herbicides are extensively used in the control of weeds and
      have widely resulted in nonpoint contamination of groundwater and soil resources.
      In the attempt to achieve better remediation for herbicide-contaminated
      resources, we investigated the reductive transformation of propachlor through
      nucleophilic substitution by dithionite (S(2)O(4)(2-)). Results showed that
      propachlor underwent rapid dechlorination in the presence of dithionite. The
      reaction was of second-order kinetics and strongly influenced by pH and
      temperature. At pH 7.0 and temperature 308K, the rate constant of propachlor
      dechlorination was estimated at 123.4+/-0.7M(-1)h(-1). Within the pH range tested
      (3.0-9.5), higher pH promoted the ionization of dithionite, resulting in a more
      active nucleophilic reagent of S(2)O(4)(2-) to enhance the propachlor
      transformation rate. Similarly, higher reaction temperature overcame the
      activation barrier of steric hindrance in propachlor structure and accelerated
      the excitation of dithionite, in which higher rate constants of propachlor
      reductive dechlorination were obtained. Dechlorination was found to be the first
      and necessary step of propachlor nucleophilic substitution by dithionite. Sulfur
      nucleophile substituted compounds, including propachlor dithionite, propachlor
      ethanesulfonic acid (ESA), and hydroxyl propachlor, were identified as the
      dechlorination products of propachlor, indicating bimolecular nucleophilic
      substitution (S(N)2) as the mechanism for propachlor transformation initiated by
      dithionite.

PMID- 21893333
TI  - Is PCBs concentration variability between and within freshwater fish species
      explained by their contamination pathways?
AB  - Many chemical, physiological, and trophic factors are known to affect
      bioaccumulation of polychlorinated biphenyls (PCBs) in biota. Understanding the
      primary factors affecting fish contamination is critical for predicting and
      assessing risks to upper-trophic level consumers, including humans. Here we
      identify PCB contamination pathways that could explain within- and between
      species variability in fish concentration levels. Three freshwater river fish
      species (barbel, chub and bream) were sampled at three sites along the Rhone
      River (France) where fish consumption is partially prohibited because of PCB
      levels exceeding the European health-based benchmark. The trophic position was
      assessed using an innovative approach based on stable isotope analyses and
      Bayesian inference, which takes into account both isotope data variability and
      parameter uncertainty. The effect of foraging habitat on fish contamination was
      addressed using stable isotope mixing models. The fish trophic position and PCB
      concentrations were found to be unrelated while the exploitation of sediment
      detrital carbon as a food source appeared to be a critical factor affecting fish
      contamination. Fish length, PCB concentration of the sediment, and individual
      fish foraging habitat (exploitation of detrital versus planktonic carbon sources)
      explained 80% of within- and between-species variability observed in PCB
      concentrations. These results, obtained for species that have overlapping TPs and
      exploit different carbon sources, reveal that the important factor in fish PCB
      contamination is not only what fish consume, but also and essentially the feeding
      location.

PMID- 21893334
TI  - Biodegradation of endosulfan by Mortieralla sp. strain W8 in soil: Influence of
      different substrates on biodegradation.
AB  - To examine the bioremediation potential of Mortierella sp. strain W8 in
      endosulfan contaminated soil, the fungus was inoculated into sterilized and
      unsterilized soil spiked with endosulfan. Wheat bran and cane molasses were used
      as substrates to understand the influence of different organic materials on the
      degradation of endosulfan in soil. Strain W8 degraded alpha- and beta-endosulfan
      in both sterilized and unsterilized soil. In unsterilized soil with wheat
      bran+W8, alpha- and beta- endosulfan were degraded by approximately 80% and 50%,
      respectively after 28 d incubation against the initial endosulfan concentration
      (3 mg kg(-1) dw). The corresponding values for alpha- and beta-endosulfan
      degradation with wheat bran only were 50% and 3%. Endosulfan diol metabolite was
      detected after 14 d incubation in wheat bran+W8 whereas it was not found with
      wheat bran only. Production of endosulfan sulfate, the main metabolite of
      endosulfan, was suppressed with wheat bran+W8 treatment compared with wheat bran
      only. It was demonstrated that wheat bran is a more suitable substrate for strain
      W8 than cane molasses. Wheat bran+W8 is a superior fungus and substrate mix for
      bioremediation in soil contaminated with endosulfan.

PMID- 21893335
TI  - Diagnostic value of intraoperative examination of sentinel lymph node in early
      cervical cancer: a prospective, multicenter study.
AB  - OBJECTIVES: Sentinel lymph node (SLN) biopsy is a surgical procedure proposed in
      early cervical cancer. This technique yields the potential interest to reduce the
      morbidity of complete lymphadenectomy, which could then be performed only in case
      of positive SLN. Intraoperative examination has a major per-operative role in
      predicting nodal involvement and preventing a second step procedure. The aim of
      this study was to assess the diagnostic value of intraoperative examination with
      frozen section (FS) or imprint cytology (IC) of SLNs in early cervical cancer.
      METHODS: Prospective study in 7 centers (01/2005-06/2007) including patients with
      stage IA1 and lymphovascular space involvement to IB1 cervical cancer (squamous
      cell carcinoma, adenocarcinoma or adenosquamous carcinoma). SLNs were detected
      with a combined method (Tc99m+blue dye) and then removed laparoscopically.
      Intraoperative examination (FS or IC) was not systematically performed but
      recommended in case of macroscopical nodal enlargement in 5 centers. Results of
      intraoperative examination were compared with final histology performed by
      Hematoxylin-Eosin-Safran staining and immunohistochemistry. The diagnostic value
      of intraoperative examination was calculated. RESULTS: One hundred and thirty
      nine patients were analyzed in the study. The combined detection rate was 97.8%
      per patient, with 454 detected SLNs. One hundred and two patients (73.4%) had an
      intraoperative examination (97 patients with FS and 5 with IC). Among patients
      with intraoperative examination, 5 SLNs were positive (all with macrometastasis
      at final histology), as compared with 22 metastatic nodes at final result. The 17
      false negative SLNs were: 4 macrometastasis, 4 micrometastasis and 9 isolated
      tumor cells. Sensitivity of the intraoperative examination per node was 20.7%
      [95%CI: 7.8%-45.4%] and the negative predictive value 93.0% [95%CI: 89.0%-95.9%].
      CONCLUSIONS: Intraoperative examination of SLNs by FS and IC has a poor
      diagnostic value. This is mainly related to micrometastasis and isolated tumor
      cells, which are not detected by intraoperative techniques. Other techniques,
      like new molecular assays, should be investigated to improve intraoperative
      assessment of SLNs.

PMID- 21893336
TI  - Integrating a relaxation response-based curriculum into a public high school in
      Massachusetts.
AB  - Academic and societal pressures result in U.S. high school students feeling
      stressed. Stress management and relaxation interventions may help students
      increase resiliency to stress and overall well-being. The objectives of this
      study were to examine the feasibility (enrollment, participation and
      acceptability) and potential effectiveness (changes in perceived stress, anxiety,
      self-esteem, health-promoting behaviors, and locus of control) of a relaxation
      response (RR)-based curriculum integrated into the school day for high school
      students. The curriculum included didactic instruction, relaxation exercises,
      positive psychology, and cognitive restructuring. The intervention group showed
      significantly greater improvements in levels of perceived stress, state anxiety,
      and health-promoting behaviors when compared to the wait list control group. The
      intervention appeared most useful for girls in the intervention group. The
      results suggest that several modifications may increase the feasibility of using
      this potentially effective intervention in high schools.

PMID- 21893337
TI  - Maternal cultural values and parenting practices: longitudinal associations with
      Chinese adolescents' aggression.
AB  - Interrelations among cultural values, parenting practices, and adolescent
      aggression were examined using longitudinal data collected from Chinese
      adolescents and their mothers. Adolescents' overt and relational aggression were
      assessed using peer nominations at Time 1 (7th grade) and Time 2 (9th grade).
      Mothers reported endorsement of cultural values (collectivism and social harmony)
      and parenting practices (psychological control and inductive reasoning) at Time
      1. While controlling for Time 1 adolescent aggression, maternal collectivism and
      social harmony indirectly and longitudinally linked to adolescent aggression
      through maternal parenting practices. Specifically, maternal collectivism was
      positively related to inductive reasoning, which, in turn, negatively related to
      adolescent overt aggression at Time 2. Similarly, maternal social harmony
      negatively related to psychological control that positively predicted later
      adolescent relational aggression. Results of the present study shed light on
      mechanisms through which culture may indirectly influence adolescent aggression.

PMID- 21893339
TI  - A syncytin-like endogenous retrovirus envelope gene of the guinea pig
      specifically expressed in the placenta junctional zone and conserved in
      Caviomorpha.
AB  - Syncytins are genes of retroviral origin that have been co-opted by mammalian
      hosts for a function in placentation. Two such genes have already been identified
      in simians, as well as two distinct, unrelated ones in Muridae and a fifth in the
      rabbit. Here we searched for similar genes in the guinea pig, which belongs to
      the Caviomorpha lineage within the Hystricognathi suborder of rodents and
      displays a placental structural organization with several characteristic features
      comparable to those of the human organ, including deep trophoblast invasion of
      maternal tissues. An in silico search for envelope (env) genes with full coding
      capacity identified a candidate gene that showed specific expression in the
      placenta, as revealed by RT-qPCR using RNAs from a large panel of tissues. This
      gene belongs to an endogenous retroviral element present at a single-copy in the
      guinea pig genome, still displaying a retroviral organization - with a degenerate
      gag and pol, but an intact env gene. In situ hybridization of guinea pig placenta
      sections demonstrated specific expression at the level of the invasive
      trophoblast-containing junctional zone, as observed in humans for syncytin-1 and
      consistent with a role in invasion of the maternal uterine tissues. The
      identified gene displays a conserved open reading frame in the Caviomorpha,
      consistent with an entry date >30 million years, and sequence analyses showed
      purifying selection of the gene. Conclusively, despite the absence of a
      demonstrated fusogenic activity, it is likely that the identified env gene - that
      we named syncytin-like env-Cav1 - exerts a physiological function possibly
      related to trophoblast invasion, in the course of caviomorph placentation.

PMID- 21893338
TI  - Real time monitoring of biomaterial-mediated inflammatory responses via
      macrophage-targeting NIR nanoprobes.
AB  - Medical implant-mediated inflammatory responses, often involving high levels of
      macrophages, are typically determined by histological analyses. These methods
      however are time consuming and require many animals to monitor the kinetics of
      inflammatory reactions and to generate reproducible outcomes. Recent studies have
      shown that activated macrophages in inflamed tissue express high levels of folate
      receptor (FR). In this study, FR-targeting NIR nanoprobes were fabricated and
      then tested for their ability to detect and quantify the extent of biomaterial
      mediated inflammatory responses in vivo. Indeed, FR-targeting nanoprobes
      preferentially accumulate on activated macrophage surfaces. When administered
      intravenously, we found that the FR-targeting nanoprobes distinctively gathered
      in the inflamed tissues and that a different extent of FR-targeting nanoprobe
      gathering could be found in tissues implanted with different types of
      biomaterials. Most importantly, we found that there was a good relationship
      between the extent of inflammatory reactions and the intensity of nanoprobe
      associated NIR signal in tissue. Our results support that FR-targeting NIR
      nanoprobes can be used to monitor and quantify the extent of macrophage
      recruitment and the degree of an implants' biocompatibility in real time.

PMID- 21893341
TI  - A combination of methotrexate and irradiation promotes cell death in NK/T-cell
      lymphoma cells via down-regulation of NF-kappaB signaling.
AB  - Nasal NK/T-cell lymphoma (NKTL) is a highly aggressive disease. Although
      radiotherapy is the first-line of treatment for NKTL, the clinical outcome is
      poor. Thus, there is a need for an effective radiosensitizer to improve the
      survival rate of patients. NF-kappaB activation contributes to cell survival as
      well as chemo- and radio-resistance in various cancer cells. In NKTL, the
      constitutive activation of NF-kappaB is also a critical factor. In the present
      study, we used two EBV-expressing NKTL cell lines (Hank-1 and NK-92) to evaluate
      the radiosensitizing effect of methotrexate (MTX), highlighting the role of NF
      kappaB. Combined treatment of MTX and IR significantly induced apoptosis and
      growth inhibition in both NKTL cells. The synergistic cytotoxicity was correlated
      with blocking nuclear NF-kappaB and suppressing expression of NF-kappaB-mediated
      anti-apoptotic proteins. These data suggest that the combined treatment with MTX
      and IR can inhibit IR-induced NF-kappaB activation in NKTL cells. Taken together,
      co-treatment with MTX and IR may provide a therapeutic advantage for patients
      with NKTL.

PMID- 21893340
TI  - A study of serum concentrations and dermal levels of NGF in atopic dermatitis and
      healthy subjects.
AB  - Nerve growth factor (NGF) was reported to be increased in the serum and skin of
      atopic dermatitis (AD) patients, to the extent that serum nerve growth factor
      levels were proposed to serve as a marker of disease severity. We studied NGF
      levels in the serum and dermis using skin microdialysis and attempted to
      correlate them with disease severity. We also examined if potential differences
      between morning and evening levels of NGF can explain the phenomenon of nocturnal
      itch. In addition, neurogenic inflammation and itch were induced using histamine
      iontophoresis in lesional and non-lesional skin and the effect of experimental
      itch on dermal NGF concentration was examined. We found that systemic (serum) and
      eczematous skin levels of NGF in AD are significantly lower in comparison to
      healthy controls. Serum NGF decreases from morning to late afternoon in both
      groups. Interestingly, serum NGF levels were correlated to disease severity in
      the morning in AD, although the NGF concentration in AD were significantly lower
      than in the healthy group. The local itch and neurogenic inflammation induction
      via experimental histamine reduced local NGF levels in the eczema and non
      lesional skin in atopics, but not in the healthy controls, where it was slightly
      increased. The higher the clinical severity of the eczema, a significantly less
      pronounced effect of neurogenic inflammation on the local levels of NGF was
      found. The availability of measurable NGF might be reduced by a higher expression
      of NGF receptors. The fluctuations of NGF levels during the day suggest a complex
      modulation of this neurotrophin, potentially linked to stress or to an altered
      neurophysiological mechanism.

PMID- 21893342
TI  - Runoff of genotoxic compounds in river basin sediment under the influence of
      contaminated soils.
AB  - Contaminated sites must be analyzed as a source of hazardous compounds in the
      ecosystem. Contaminant mobility in the environment may affect sources of surface
      and groundwater, elevating potential risks. This study looked at the genotoxic
      potential of samples from a contaminated site on the banks of the Taquari River,
      RS, Brazil, where potential environmental problems had been identified
      (pentachlorophenol, creosote and hydrosalt CCA). Samplers were installed at the
      site to investigate the drainage material (water and particulate soil matter)
      collected after significant rainfall events. Organic extracts of this drained
      material, sediment river samples of the Taquari River (interstitial water and
      sediment organic extracts) were evaluated by the Salmonella/microsome assay to
      detect mutagenicity and by Allium cepa bioassays (interstitial water and whole
      sediment samples) to detect chromosomal alterations. Positive mutagenicity
      results in the Salmonella/microsome assay of the material exported from the area
      indicate that contaminant mixtures may have drained into the Taquari River. This
      was confirmed by the similarity of mutagenic responses (frameshift indirect
      mutagens) of organic extracts from soil and river sediment exported from the main
      area under the influence of the contaminated site. The Allium cepa test showed
      significant results of cytotoxicity, mutagenic index and chromosome aberration in
      the area under the same influence. However, it also showed the same similarity in
      positive results at an upstream site, which probably meant different
      contaminants. Chemical compounds such as PAHs, PCF and chromium, copper and
      arsenic were present in the runoff of pollutants characteristically found in the
      area. The strategy employed using the Salmonella/microsome assay to evaluate
      effects of complex contaminant mixtures, together with information about the main
      groups of compounds present, allowed the detection of pollutant dispersion routes
      from the contaminated site to the Taquari River sediment.

PMID- 21893343
TI  - Cardiopulmonary exercise test in patients with subacute pulmonary emboli.
AB  - OBJECTIVE: Patients presenting with suspected pulmonary embolism (PE) may present
      a challenge, particularly if diagnostic testing is not immediately available or
      clinically not indicated (iodine allergy, pregnancy, renal dysfunction). These
      patients have abnormal regional gas exchange that can be recognized by a
      cardiopulmonary exercise test (CPET), which may become helpful in their
      evaluation. METHODS: A retrospective analysis was performed of outpatients
      evaluated for subacute exertional dyspnea of 2 to 12 weeks duration with a test
      for PE and CPET. A total of 108 patients met inclusion criteria. Thirty patients
      (27.8%) had confirmed PE. RESULTS: The patients with PE had increased nadir
      ventilatory equivalent ratio for carbon dioxide (VE/VCO(2)), decreased peak
      oxygen uptake/predicted, and decreased end exercise saturation (P < .005 for
      all). All patients but 1 had normal breathing reserve (>15%). A normal nadir
      VE/VCO(2) excluded PE with 100% sensitivity. By using a "flow chart strategy,"
      the exercise test had 92.8% sensitivity and 92.1% specificity for PE. Eight
      patients with PE died during follow-up (3.8 +/- 4.6 years), 6 of PE-related
      causes. Peak VO(2)/kg was the best predictor of all-cause mortality and nadir
      VE/VCO(2) for PE-related mortality. There were no serious complications from any
      of the exercise tests. CONCLUSION: PE may be excluded by a normal nadir VE/VCO(2)
      in patients presenting with subacute dyspnea. A combination of decreased peak
      VO(2)/kg, increased nadir VE/VCO(2), normal breathing reserve, and exercise
      induced desaturation may be sensitive and specific for PE. CPET may assist in
      identifying subacute PE in patients with contraindications to use of computed
      tomography angiography or ventilation perfusion scans.

PMID- 21893344
TI  - Superior vena cava and right atrium wall infective endocarditis in patients
      receiving hemodialysis.
AB  - Infective endocarditis is significantly more common and causes greater morbidity
      and mortality in patients receiving hemodialysis than in the general population.
      Episodes of bacteremia during hemodialysis are primarily the result of frequent
      vascular access through an arteriovenous fistula, a vascular graft, or an
      indwelling vascular catheter. This leads to dialysis access infection and
      secondary bacteremia. We describe 4 cases of patients receiving hemodialysis,
      with an indwelling intravascular dialysis catheter, who developed right-sided
      endocarditis with vegetations located exclusively on the superior vena cava and
      right atrium wall. All patients had persistent bacteremia with Staphylococcus,
      secondary to an indwelling intravascular hemodialysis catheter, which led to
      seeding of the right-sided cardiac wall, causing infective endocarditis. The
      rates of acceptance for hemodialysis are increasing, along with improved survival
      in this group of patients. This will probably lead to an increase in the
      incidence of infective endocarditis, with atypical presentations such as superior
      vena cava and right-sided cardiac wall endocarditis.

PMID- 21893345
TI  - Inexperienced nurses and doctors are equally efficient in managing the airway in
      a manikin model.
AB  - OBJECTIVE: The aim of the present study was to investigate whether minimally
      trained medical and nursing school graduates would be equally efficient in
      placing a laryngeal mask airway (LMA) and in intubating the trachea with the
      Macintosh blade or a videolaryngoscope in a manikin model. Airway management is
      an essential skill for both physicians and nurses who may be confronted with a
      critically ill patient, because in the emergency department the airway is not
      exclusively managed by medical personnel. Several studies have shown that other
      healthcare professionals are not any less efficient in securing the airway.
      METHODS: Ninety-six graduates from medical and nursing faculties comprised our
      study population. After a brief educational session, participants were randomly
      allocated into 3 groups to secure the airway in manikins with 3 techniques: LMA
      (The Laryngeal Mask Company Limited, Buckinghamshire, UK) insertion and
      intubation with the Macintosh blade and with a videolaryngoscope (GlideScope,
      Verathon Inc, Bothell, WA). The number of attempts until the first successful
      intubation, time required for the first successful attempt, and severity of
      dental trauma were assessed. RESULTS: No statistically significant difference was
      observed between physicians and nurses in the number of attempts and in the time
      required for the first successful attempt with any of the 3 techniques studied.
      From the 3 techniques studied, LMA placement was the fastest (P < .001). No
      significant difference was observed between physicians and nurses in the severity
      of dental trauma. CONCLUSION: Nurses are as efficient as physicians in managing
      the airway safely and adequately with the 3 different techniques in manikins.

PMID- 21893347
TI  - Infants' sensitivity to pictorial depth cues: a review and meta-analysis of
      looking studies.
AB  - This paper reviews habituation-dishabituation and preferential-looking studies on
      the emergence of sensitivity to pictorial depth cues in infancy. This research
      can be subdivided into two groups. While one group of studies has established
      responsiveness to pictorial depth cues at 3-5 months of age, the other has found
      that the ability to extract pictorial 3D information emerges at about 6 months.
      In the former, young infants were tested for their ability to distinguish between
      displays that differ in spatial information provided by pictorial depth cues. The
      results of these studies might demonstrate that 3-5-month-old infants perceive
      spatial layout from pictorial cues. It is possible, however, that the infants in
      these studies responded primarily to low-level, two-dimensional stimulus
      differences. In contrast, the second group of studies controlled for the
      potential influence of lower-level stimulus features on the infants' experimental
      performance and more unambiguously demonstrated sensitivity to pictorial depth
      information in infants 6 months of age and older. In sum, the divergent findings
      of studies in this area may be resolved by assuming substantial developmental
      progress in infant sensitivity to pictorial depth cues during the first months of
      life.

PMID- 21893346
TI  - Modulation of the humoral immune response by targeting CD40 and FcgammaRII/III;
      delivery of soluble but not particulate antigen to CD40 enhances antibody
      responses with a Th1 bias.
AB  - Targeted delivery of antigen improves immunogenicity and can obviate the use of
      adjuvants. In addition to molecular targeting based on affinity interactions,
      particle-based antigen targeting to myeloid cells is also an efficient means to
      enhance immune responses. We compared the efficiency of targeting a model
      antigen, streptavidin, to CD40 and low affinity Fc gamma receptors II and III,
      either in a soluble or in a particulate form. Single chain fragments targeting
      these receptors were used to generate soluble tetramers with streptavidin or to
      decorate streptavidin coated nanobeads, and mice were immunized with the
      different formulations. Whereas particulate presentation of streptavidin enhanced
      total IgG1 and IgG2a levels, overall antigen specific antibody production
      increased in the case of targeted soluble antigen only, as assessed by reverse
      protein arrays and ELISPOT. In particular, soluble CD40 targeted antigen induced
      the strongest IgG2a responses, suggesting a Th1 bias compared to FcgammaRII/III
      targeting. Combined targeting to these receptors did not further increase
      immunogenicity. Thus, in our model, affinity targeting of soluble antigen to CD40
      proved to be superior to particle-mediated delivery both in terms of antibody
      quantity and quality.

PMID- 21893348
TI  - Gaze aversion during social interaction in preterm infants: a function of
      attention skills?
AB  - Preterm infants avert their gaze more often and for longer periods in early
      social interactions compared to full term infants. In previous studies this
      finding is interpreted as being a function of the higher degree of parental
      stimulation that is often found in parents of preterm children. The current study
      explores an additional hypothesis. Since the development of general visual
      attention abilities is found to be less optimal in preterm children, it is
      possible that less optimal maturation of attention abilities partially explains
      the elevated gaze aversion in a social context. Therefore, the current study
      investigated the association between gaze aversion in a social context and the
      ability to disengage and shift visual attention in a non-social context in 20
      preterm and 42 full term infants aged 4 and 6 months. Results confirm that
      preterm infants are slower to shift their attention in a non-social context and
      that they avert their gaze more often in a social context compared to full term
      children. Furthermore, more frequent gaze aversion during social interaction at 6
      months was related to longer disengagement and the shifting of attention at 4 and
      6 months, but only within the preterm group. The results suggest that attention
      maturation is less optimal in preterm children; this can be observed in a non
      social as well as a social context. Less attention maturation in preterm children
      can negatively influence the amount of time they can stay actively involved in
      social interaction.

PMID- 21893349
TI  - Decreased serotonin content and reduced agonist-induced aggregation in platelets
      of patients chronically medicated with SSRI drugs.
AB  - BACKGROUND: Chronic treatment with selective serotonin reuptake inhibitors
      (SSRIs) reduces the risk and severity of cardiovascular diseases. SSRIs block the
      serotonin transporter, thereby inhibiting serotonin (5-HT) uptake into
      presynaptic neurons as well as into platelets where 5-HT is stored in dense
      granules. When 5-HT is released in response to agonists it enhances platelet
      aggregation induced by injury-related signals. Chronic administration of SSRIs
      may thus reduce platelet aggregability secondary to depletion of platelets'
      serotonin stores. METHODS: The study included ten DSM-IV-TR major depression
      (MDD) and four obsessive compulsive disorder (OCD) patients and fourteen healthy
      untreated age- and sex-matched controls. The patients were chronically medicated
      (6-108 months) with various SSRIs. Platelet serotonin content was assessed in
      fresh samples of platelet rich plasma (PRP) using radioimmunoassay. ADP,
      collagen, arachidonic acid and epinephrine were used as inducers of platelet
      aggregation measured in PRP by turbometric method in a microplate reader.
      RESULTS: Lower platelet serotonin content (66%; p<0.05) and lower ADP, collagen
      or epinephrine-induced platelet aggregation (10-52%; p<0.05) were detected in PRP
      of SSRI-medicated patients, while no such effect was obtained with arachidonic
      acid. LIMITATIONS: The small sample size and the co-treatment with non-SSRI drugs
      such as benzodiazepines. CONCLUSION: Patients chronically medicated with SSRIs
      exhibit lower platelet 5-HT content and reduced platelet aggregation induced by
      ADP, collagen and epinephrine, but not by arachidonic acid. Our observations may
      explain the increased bleeding risk associated with chronic SSRI treatment as
      well as the reported beneficial effect of SSRIs in prevention of recurrent
      myocardial infarction.

PMID- 21893350
TI  - Paraoxonase and arylesterase activity and total oxidative/anti-oxidative status
      in patients with chronic adenotonsillitis.
AB  - OBJECTIVES: The aim of this study was to investigate serum paraoxonase,
      arylesterase activities along with determination of oxidative status via
      measurement of total oxidant status (TOS), total antioxidant status (TAS) and
      oxidative stress index (OSI) in children with recurrent adenotonsillitis during
      pre- and post-adenotonsillectomy period and to compare results with data from
      healthy subjects. METHODS: We performed a prospective controlled trial on
      adenoidectomy and/or tonsillectomy patients. A total of 47 subjects, including 22
      patients with recurrent adenotonsillitis and 25 healthy controls were enrolled in
      this study. Peripheral venous blood samples were taken from patients before
      adenotonsillectomy and a second sample was obtained in first month
      postoperatively. In the control group, blood samples from healthy volunteers were
      collected for one time only. Serum paraoxonase, arylesterase activities, TOS, TAS
      and OSI levels were measured. RESULTS: Paraoxonase, arylesterase activity, TAS
      and TOS levels were significantly higher in preoperative group compared to
      control group (P<0.001, P=0.003, 0.003 and 0.005, respectively). However, OSI
      level was similar in preoperative group compared to control group (P=0.25). In
      the post-operative group, paraoxonase, arylesterase activities, TAS and OSI
      levels were lower as compared to preoperative group but differences were
      statistically insignificant (P=0.483, 0.265, 0.149 and 0.090, respectively). TOS
      level in post-operative group was significantly lower than the preoperative group
      (P<0.001). In the post-operative group, paraoxonase and arylesterase activities
      were significantly higher as compared to control group (P=0.004 and 0.02,
      respectively). TOS and OSI levels were significantly lower in post-operative
      group compared to control group (P=0.001 and 0.02, respectively). However, TAS
      was similar between post-operative and control groups (P=0.464). CONCLUSIONS:
      Based on data obtained from this study, we may state that paraoxonase,
      arylesterase activities with TAS, TOS and OSI levels of patients with chronic
      adenotonsillitis shows alterations due to oxidant/antioxidant imbalance induced
      by frequent infections.

PMID- 21893351
TI  - Early prelingual auditory development and speech perception at 1-year follow-up
      in Mandarin-speaking children after cochlear implantation.
AB  - OBJECTIVE: The primary purpose of the current study was to evaluate early
      prelingual auditory development (EPLAD) and early speech perception
      longitudinally over the first year after cochlear implantation in Mandarin
      speaking pediatric cochlear implant (CI) recipients. Outcome measures were
      designed to allow comparisons of outcomes with those of English-speaking
      pediatric CI recipients reported in previous research. METHOD: A hierarchical
      outcome assessment battery designed to measure EPLAD and early speech perception
      was used to evaluate 39 pediatric CI recipients implanted between the ages of 1
      and 6 years at baseline and 3, 6, and 12 months after implantation. The battery
      consists of the Mandarin Infant-Toddler Meaningful Auditory Integration Scale
      (ITMAIS), the Mandarin Early Speech Perception (MESP) test, and the Mandarin
      Pediatric Speech Intelligibility (MPSI) test. The effects of age at implantation,
      duration of pre-implant hearing aid use, and Mandarin dialect exposure on
      performance were evaluated. EPLAD results were compared with the normal
      developmental trajectory and with results for English-speaking pediatric CI
      recipients. MESP and MPSI measures of early speech perception were compared with
      results for English-speaking recipients obtained with comparable measures.
      RESULTS: EPLAD, as measured with the ITMAIS/MAIS, was comparable in Mandarin- and
      English-speaking pediatric CI recipients. Both groups exceeded the normal
      developmental trajectory when hearing age in CI recipients and chronological age
      in normal were equated. Evidence of significant EPLAD during pre-implant hearing
      aid use was observed; although at a more gradual rate than after implantation.
      Early development of speech perception, as measures with the MESP and MPSI tests,
      was also comparable for Mandarin- and English-speaking CI recipients throughout
      the first 12 months after implantation. Both Mandarin dialect exposure and the
      duration of pre-implant hearing aid use significantly affected measures of early
      speech perception during this time period. CONCLUSIONS: EPLAD and early speech
      perception exhibited similar patterns of improvement during the first 12 months
      after early cochlear implantation. The duration of pre-implant hearing aid use
      had a significant positive effect on both categories of outcome measures.
      Consistent post-implant EPLAD trajectories and early speech perception results
      provide objective evidence that can guide best practices in early intervention
      protocols.

PMID- 21893352
TI  - Cochlear implantation in children with cerebral palsy.
AB  - OBJECTIVE: Few studies have looked at the outcomes of children with complex needs
      following cochlear implantation. Increasing evidence supports the case for
      implantation in these children. To date there is very little evidence available
      evaluating the role of cochlear implantation in children with cerebral palsy. In
      this paper we look at the Manchester Cochlear Implant Programme's experience of
      implantation in 36 children with cerebral palsy. METHODS: A retrospective review
      of prospectively collected data for all children with cerebral palsy was
      undertaken. Cognitive and physical disability was scored by members of the
      cochlear implant team. A modified version of Geers and Moogs 1987 Speech
      Reception Score was used to assess outcome. Data was analysed looking at the
      relationship between cognitive and physical impairment, age at implantation and
      the SRS outcomes. RESULTS: This study demonstrated that children with cerebral
      palsy and a mild cognitive impairment do significantly better following
      implantation than those with a severe impairment (p=0.008). Children with mild
      physical impairment did not appear to do significantly better than those with
      moderate or severe impairments (mild versus severe p=0.13). Age at implantation
      was not a significant prognostic factor in this study group. CONCLUSIONS:
      Children with complex needs are increasingly being referred for consideration of
      cochlear implantation. Further research is required to help guide candidacy, but
      each case must be considered individually. Higher functioning does appear to be
      the most important prognostic indicator regarding outcome but the effect of
      modest improvement in sound perception should not be underestimated.

PMID- 21893354
TI  - A cross-sectional analysis of age and sex patterns in grip strength, tooth loss,
      near vision and hearing levels in Chinese aged 50-74 years.
AB  - By focusing on four health variables, handgrip strength, near visual acuity,
      tooth loss and hearing level, this study examined the different patterns of age
      related changes in these variables in Chinese aged from 50 to 74 years, as well
      as explored the relationship among the variables in a cross-sectional sample of
      2006 individuals. The data exhibited high quality with a low missing rate of
      under 5% in any age groups for each variable. Effects of age and sex on the
      changes in the four health variables were assessed using multiple regression
      models with age and sex interactions included. Upon the highly significant
      effects of age on all four measurements, we observed substantially higher grip
      strength for men who, however, exhibited a faster age-related decline than for
      women. No sex difference or age-sex interaction was found in the number of teeth
      lost. Near visual acuity displayed a faster age-related decline in women than in
      men but neither the overall sex difference nor age-sex interaction reached
      statistical significance. For hearing function, while no sex difference was found
      at middle frequency, women had better sensitivity at high frequency and men were
      more sensitive at low frequency. Multivariate analysis did not support an age
      related common mechanism underlying the four health variables.

PMID- 21893353
TI  - Nitric oxide and protein phosphatase 2A provide novel therapeutic opportunities
      in ER-negative breast cancer.
AB  - Basal-like breast cancer is an aggressive disease with limited therapeutic
      options because these tumors frequently express the 'triple-negative' phenotype.
      We have recently reported that inducible nitric oxide synthase (NOS2) is a strong
      predictor of survival in patients with estrogen receptor negative [ER(-)] breast
      cancer, and that NOS2 expression is correlated with a basal-like phenotype.
      Recent reports also describe the pro-tumor effects of NO in breast and many other
      types of cancer. NO promotes cancer progression by activating several oncogenic
      signaling pathways such as extracellular signal-regulated kinases (ERK)-1/2,
      phosphoinositide 3-kinases (PI3K)/Akt, and c-Myc. Protein phosphatase 2A (PP2A)
      is a tumor suppressor that negatively regulates the same cancer-related signaling
      pathways that are activated by NO. PP2A activity is suppressed in tumor cells,
      but potential pharmacological agents have recently been described to increase
      PP2A activity in ER(-) breast cancer cells. We examine here the various functions
      of NO and PP2A in breast cancer and propose a novel mechanism by which activation
      of PP2A antagonizes NO signaling that promotes ER(-) breast cancer.

PMID- 21893355
TI  - Platelet-derived chemokines, PF-4 and RANTES, are significantly increased in
      hemodynamically significant degenerative aortic stenosis.

PMID- 21893356
TI  - Horse owners' biosecurity practices following the first equine influenza outbreak
      in Australia.
AB  - A cross-sectional study was conducted involving 759 Australian horse owners to
      determine their biosecurity practices and perceptions one year after the 2007
      equine influenza outbreak and to investigate the factors influencing these
      perceptions and practices. A web link to an online questionnaire was sent to 1224
      horse owners as a follow-up to a previous study to obtain information about
      biosecurity perceptions and practices, impacts of the 2007 EI outbreak,
      demographic information and information about horse industry involvement. Ordinal
      logistic regression analyses were conducted to determine factors associated with
      poor biosecurity practices. Biosecurity compliance (low, medium, high), as
      determined by horse owners' responses to a 16-item question on the frequency of
      various biosecurity measures, was used as the outcome variable in ordinal
      logistic regression analyses. Variables with a univariable p-value <=0.2 were
      eligible for inclusion in multivariable models built using a manual stepwise
      approach. Variables with a p-value <0.05 in multivariable models were retained in
      the final model. Two potential confounders - age and gender of participants -
      were included in the final model irrespective of their p-values. Thirty percent
      of the respondents had low biosecurity compliance and were performing biosecurity
      practices 'not very often' or 'never'. Younger people, people with two or more
      children, those who were not involved with horses commercially and those who had
      no long-term business impacts resulting from the 2007 EI outbreak were more
      likely to have lower biosecurity compliance. People who were not fearful of a
      future outbreak of equine influenza in Australia and those who thought their
      current hygiene and access control practices were not very effective in
      protecting their horses also had poor biosecurity practices. In this
      observational study we identified factors associated with a group of horse owners
      with low levels of biosecurity compliance. As this cross-sectional study only
      assesses associations, the identified factors should be further investigated in
      order to be considered in the design of extension activities to increase horse
      owners' biosecurity compliance.

PMID- 21893358
TI  - Does better disease management in primary care reduce hospital costs? Evidence
      from English primary care.
AB  - We apply cross-sectional and panel data methods to a database of 5 million
      patients in 8000 English general practices to examine whether better primary care
      management of 10 chronic diseases is associated with reduced hospital costs. We
      find that only primary care performance in stroke care is associated with lower
      hospital costs. Our results suggest that the 10% improvement in the general
      practice quality of stroke care between 2004/5 and 2007/8 reduced 2007/8 hospital
      expenditure by about L130 million in England. The cost savings are due mainly to
      reductions in emergency admissions and outpatient visits, rather than to lower
      costs for patients treated in hospital or to reductions in elective admissions.

PMID- 21893357
TI  - School quality and the education-health relationship: evidence from blacks in
      segregated schools.
AB  - In this paper, we estimate the effect of school quality on the relationship
      between schooling and health outcomes using the substantial improvements in the
      quality of schools attended by black students in the segregated southern states
      during the mid-1900s as a source of identifying variation. Using data from the
      National Health Interview Survey, our results suggest that improvements in school
      quality, measured as the pupil-teacher ratio, average teachers' wage, and length
      of the school year, amplify the beneficial effects of education on several
      measures of health in later life, including self-rated health, smoking, obesity,
      and mortality.

PMID- 21893359
TI  - Biocontrol as a strategy to reduce the impact of ochratoxin A and Aspergillus
      section Nigri in grapes.
AB  - The efficacy of two strains of Kluyveromyces thermotolerans in preventing the
      growth and ochratoxin A (OTA) accumulation of ochratoxigenic fungi both "in
      vitro" and "in situ" was evaluated. The data from this study showed that both
      yeast strains were able to control Aspergillus carbonarius and A. niger aggregate
      species growth and ochratoxin A accumulation. The inhibitory effects were
      dependent on the ochratoxigenic species, yeast strains, a(w) and temperature
      evaluated and their interactions. Over all conditions assayed, ochratoxin A
      accumulation was reduced from 3% to 100% and the growth rate from 11% to 82.5%,
      depending on conditions. These results are promising for future development of a
      bio-pesticide.

PMID- 21893360
TI  - Combined effect of selected non-thermal technologies on Escherichia coli and
      Pichia fermentans inactivation in an apple and cranberry juice blend and on
      product shelf life.
AB  - The combination of novel, non-thermal technologies for preservation purposes is a
      recent trend in food processing research. In the present study, non-thermal
      hurdles such as ultraviolet light (UV) (5.3 J/cm2), high intensity light pulses
      (HILP) (3.3 J/cm2), pulsed electric fields (PEF) (34 kV/cm, 18 Hz, 93 MUs) or
      manothermosonication (MTS) (4bar, 43  degrees C, 750 W, 20 kHz) were examined.
      The objective was to establish the potential of these technologies, applied
      individually or in paired sequences, to inactivate Escherichia coli and Pichia
      fermentans inoculated in a fresh blend of apple and cranberry juice. The shelf
      life evaluation of selected non-thermally treated samples was conducted over 35
      days and compared to pasteurised samples and untreated juices. All treatments
      applied individually significantly reduced (1.8-6.0 log cfu/ml) microbial counts
      compared to the untreated sample (p<0.01). Furthermore, UV treatment produced
      significantly greater inactivation (p<0.05) for E. coli compared to P.
      fermentans. Combinations of non-thermal hurdles consisting of UV or HILP followed
      by either PEF or MTS resulted in comparable reductions for both microorganisms (p
      >= 0.05) to those observed in thermally pasteurised samples (approx. 6 log
      cfu/ml). Thermally pasteurised samples had a shelf life exceeding 35 days, while
      that of UV+PEF and HILP+PEF-treated samples was 14 and 21 days, respectively.
      These results indicate that combinations of these non-thermal technologies could
      successfully reduce levels of E. coli and P. fermentans in apple and cranberry
      juice, although optimisation is required in order to further extend shelf life.

PMID- 21893361
TI  - Actual distribution of Cronobacter spp. in industrial batches of powdered infant
      formula and consequences for performance of sampling strategies.
AB  - The actual spatial distribution of microorganisms within a batch of food
      influences the results of sampling for microbiological testing when this
      distribution is non-homogeneous. In the case of pathogens being non-homogeneously
      distributed, it markedly influences public health risk. This study investigated
      the spatial distribution of Cronobacter spp. in powdered infant formula (PIF) on
      industrial batch-scale for both a recalled batch as well a reference batch.
      Additionally, local spatial occurrence of clusters of Cronobacter cells was
      assessed, as well as the performance of typical sampling strategies to determine
      the presence of the microorganisms. The concentration of Cronobacter spp. was
      assessed in the course of the filling time of each batch, by taking samples of
      333 g using the most probable number (MPN) enrichment technique. The occurrence
      of clusters of Cronobacter spp. cells was investigated by plate counting. From
      the recalled batch, 415 MPN samples were drawn. The expected heterogeneous
      distribution of Cronobacter spp. could be quantified from these samples, which
      showed no detectable level (detection limit of -2.52 log CFU/g) in 58% of
      samples, whilst in the remainder concentrations were found to be between -2.52
      and 2.75 log CFU/g. The estimated average concentration in the recalled batch was
      -2.78 log CFU/g and a standard deviation of 1.10 log CFU/g. The estimated average
      concentration in the reference batch was -4.41 log CFU/g, with 99% of the 93
      samples being below the detection limit. In the recalled batch, clusters of cells
      occurred sporadically in 8 out of 2290 samples of 1g taken. The two largest
      clusters contained 123 (2.09 log CFU/g) and 560 (2.75 log CFU/g) cells. Various
      sampling strategies were evaluated for the recalled batch. Taking more and
      smaller samples and keeping the total sampling weight constant, considerably
      improved the performance of the sampling plans to detect such a type of
      contaminated batch. Compared to random sampling, stratified random sampling
      improved the probability to detect the heterogeneous contamination.

PMID- 21893362
TI  - Comparison of healthcare costs between local and immigrant HIV populations living
      in Southern Alberta, Canada.
AB  - OBJECTIVE: To compare the direct cost of care for Canadian and non-Canadian born
      HIV patients accessing initial HIV care. METHODS: Drug, inpatient, and outpatient
      costs were collected for patients initiating HIV care at the Southern Alberta
      Clinic between 1/1/2000 and 3/31/2008 and followed until 3/31/2009.
      Demographic/clinical characteristics were obtained at initial visit. Country of
      birth determined Canadian (CBP) vs. foreign born (FBP) patients. Costs are mean
      cost per patient per month (PPPM) in 2009 Cdn$. RESULTS: Of 281 patients, 103
      were FBP. 86% were born in sub-Saharan Africa. FBP were more likely to be female
      (87% vs. 50%), younger (median 33 vs. 38 years), and heterosexual (93 vs.
      35%)(all p<.01) compared to CBP. 74% FBP had CD4<350/mm(3) at initial visit
      compared to 61% of CBP (p<.05). Subsequent health outcomes for FBP/CBP were
      similar. Total mean costs PPPM were higher for CBP ($1174 vs. $1067, p<.05), and
      higher for all CD4 categories primarily due to the costs of non-HIV admissions
      among CBP injecting drug users (IDU), a risk group not represented within the FBP
      population of this study. Drugs costs were higher for FBP but lower for inpatient
      and outpatient costs. CONCLUSIONS: Once engaged in regular HIV treatment and
      care, costs and outcomes for FBP were not significantly higher than CBP. Policy
      decisions concerning FBP with HIV should not be based solely on cost issues.

PMID- 21893363
TI  - Chemotherapy in elderly patients with advanced non-small cell lung cancer.
AB  - Because of increasing life expectancy and of higher risk of cancer with ageing,
      lung cancer in elderly is a frequent disease. For a long time nihilism influenced
      treatment decisions in elderly patients with advanced non-small cell lung cancer.
      Since the beginning of the last decade single agent chemotherapy has been
      accepted as standard of care, vinorelbine and gemcitabine being the most
      frequently used drugs in Europe and US, docetaxel in Japan. Platinum-based
      doublets have been shown to be superior to monotherapy in young and fit patients
      with advanced non-small cell lung cancer. Although there were some indications
      from subgroup analyses of clinical trials not specifically dedicated to elderly
      patients that a platinum-based doublet might also benefit to older patients,
      there was no definitive proof of concept until ASCO meeting 2010. At this meeting
      results of a phase 3 trial showed that PS 0-2 patients, aged 70-89 years drove a
      significant benefit from a treatment with carboplatin associated to weekly
      paclitaxel compared to a monotherapy. Thus, the paradigm of treatment in elderly
      patients should perhaps be modified from a single agent to doublet chemotherapy.
      Whether other platinum-based doublets would provide the same benefit as the
      specific one studied remains to be evaluated.

PMID- 21893364
TI  - Trends in incidence of small cell lung cancer and all lung cancer.
AB  - BACKGROUND: The incidence of small cell lung cancer (SCLC) is often quoted as
      'around 20%' of all lung cancers but is reportedly decreasing over time. We
      analysed the trends in incidence of SCLC and compared these with the trends in
      lung cancer overall among males and females in South East England. METHODS: We
      identified 237,792 patients diagnosed with lung cancer (ICD-10 C33-C34) between
      1970 and 2007. We used a Poisson regression age-cohort model to estimate the age
      specific rates in the 1890-1960 birth cohorts. We computed age-standardised
      incidence rates using the European standard population. In addition, we analysed
      the trends of lung cancer subtypes according to morphology. RESULTS: In the most
      recent time period, SCLC accounted for 10% and 11% of cases of all lung cancer
      among males and females, respectively. Among the morphologically specified lung
      cancers, SCLC accounted for 15% and 17% among males and females, respectively.
      There was a decrease of SCLC incidence over time and by birth cohort in both
      sexes. The decrease in SCLC was more marked than that in all lung cancers.
      CONCLUSION: The decrease in SCLC incidence rates may reflect decreases in the
      prevalence of cigarette smoking, and changes in the type of cigarettes smoked.

PMID- 21893365
TI  - Stimulation of B7-H3 (CD276) directs the differentiation of human marrow stromal
      cells to osteoblasts.
AB  - Previous studies showed that B7-H3 (CD276), a cytokine involved in the activation
      of T lymphocytes, regulates murine bone formation. However, the role of B7-H3 in
      bone formation is barely understood. Herewith, we report, that stimulation of B7
      H3 promotes the differentiation of human marrow stromal cells (hMSCs) to
      osteoblasts. With 4H7, a new monoclonal antibody against human B7-H3, we have
      identified B7-H3 is located on the surface of human marrow stromal cells.
      Evermore, we have found that increase of B7-H3 levels are correlated with the
      differentiation course of hMSCs. Stimulation of B7-H3 with 4H7 antibody
      considerably increases the numbers of osteoblasts generated from the hMSCs in the
      presence of inducing medium containing dexamethasone, sodium beta
      glycerophosphate and l-ascorbic acid. 4H7 treatments significantly increase
      osteoblast markers including alkaline phosphatase (ALP), and osteocalcin (OC)
      after day 7 and day 14 of the inducing hMSCs differentiation. The numbers of
      mineralized nodules of osteoblasts have been remarkly increased after 21 days of
      induced differentiation of hMSCs. However, stimulation effects of 4H7 antibody on
      membrane B7-H3 has been eliminated by addition of B7-H3Fc fusion protein. These
      results indicate 4H7 antibody specifically stimulates the membrane B7-H3 and
      directs the differentiation of hMSCs. Furthermore, our study also shows that
      stimulation of B7-H3 increases the expression of osteoprotein (OPG), and
      decreases the expression of its cognate ligand, the receptor activator of nuclear
      factor kappaB ligand (RANKL).

PMID- 21893366
TI  - Expression of a cloned sweet potato catalase SPCAT1 alleviates ethephon-mediated
      leaf senescence and H2O2 elevation.
AB  - In this report a full-length cDNA, SPCAT1, was isolated from ethephon-treated
      mature L3 leaves of sweet potato. SPCAT1 contained 1479 nucleotides (492 amino
      acids) in its open reading frame, and exhibited high amino acid sequence
      identities (ca. 71.2-80.9%) with several plant catalases, including Arabidopsis,
      eggplant, grey mangrove, pea, potato, tobacco and tomato. Gene structural
      analysis showed that SPCAT1 encoded a catalase and contained a putative conserved
      internal peroxisomal targeting signal PTS1 motif and calmodulin binding domain
      around its C-terminus. RT-PCR showed that SPCAT1 gene expression was enhanced
      significantly in mature L3 and early senescent L4 leaves and was much reduced in
      immature L1, L2 and completely yellowing senescent L5 leaves. In dark- and
      ethephon-treated L3 leaves, SPCAT1 expression was significantly enhanced
      temporarily from 0 to 24h, then decreased gradually until 72h after treatment.
      SPCAT1 gene expression levels also exhibited approximately inverse correlation
      with the qualitative and quantitative H(2)O(2) amounts. Effector treatment showed
      that ethephon-enhanced SPCAT1 expression was repressed by antioxidant reduced
      glutathione, NADPH oxidase inhibitor diphenylene iodonium (DPI), calcium ion
      chelator EGTA and de novo protein synthesis inhibitor cycloheximide. These data
      suggest that elevated reactive oxygen species H(2)O(2), NADPH oxidase, external
      calcium influx and de novo synthesized proteins are required and associated with
      ethephon-mediated enhancement of sweet potato catalase SPCAT1 expression.
      Exogenous application of expressed catalase SPCAT1 fusion protein delayed or
      alleviated ethephon-mediated leaf senescence and H(2)O(2) elevation. Based on
      these data we conclude that sweet potato SPCAT1 is an ethephon-inducible
      peroxisomal catalase, and its expression is regulated by reduced glutathione,
      DPI, EGTA and cycloheximide. Sweet potato catalase SPCAT1 may play a
      physiological role or function in cope with H(2)O(2) homeostasis in leaves caused
      by developmental cues and environmental stimuli.

PMID- 21893367
TI  - Hallucinogenic drugs in pre-Columbian Mesoamerican cultures.
AB  - INTRODUCTION: The American continent is very rich in psychoactive plants and
      fungi, and many pre-Columbian Mesoamerican cultures used them for magical,
      therapeutic and religious purposes. OBJECTIVES: The archaeological, ethno
      historical and ethnographic evidence of the use of hallucinogenic substances in
      Mesoamerica is reviewed. RESULTS: Hallucinogenic cactus, plants and mushrooms
      were used to induce altered states of consciousness in healing rituals and
      religious ceremonies. The Maya drank balche (a mixture of honey and extracts of
      Lonchocarpus) in group ceremonies to achieve intoxication. Ritual enemas and
      other psychoactive substances were also used to induce states of trance. Olmec,
      Zapotec, Maya and Aztec used peyote, hallucinogenic mushrooms (teonanacatl:
      Psilocybe spp) and the seeds of ololiuhqui (Turbina corymbosa), that contain
      mescaline, psilocybin and lysergic acid amide, respectively. The skin of the toad
      Bufo spp contains bufotoxins with hallucinogenic properties, and was used since
      the Olmec period. Jimson weed (Datura stramonium), wild tobacco (Nicotiana
      rustica), water lily (Nymphaea ampla) and Salvia divinorum were used for their
      psychoactive effects. Mushroom stones dating from 3000 BC have been found in
      ritual contexts in Mesoamerica. Archaeological evidence of peyote use dates back
      to over 5000 years. Several chroniclers, mainly Fray Bernardino de Sahagun,
      described their effects in the sixteenth century. CONCLUSIONS: The use of
      psychoactive substances was common in pre-Columbian Mesoamerican societies.
      Today, local shamans and healers still use them in ritual ceremonies in
      Mesoamerica.

PMID- 21893368
TI  - Epilepsy in the process of artistic creation of Dostoevsky.
AB  - INTRODUCTION: Fyodor M. Dostoevsky (Moscow, 1821-Saint Petersburg, 1881) suffered
      epilepsy throughout his full literary career. The aim here is to understand his
      condition in light of his novels, correspondence and his contemporaries' accounts
      as well as by later generations of neurologists. DEVELOPMENT: From Murin and
      Ordynov (The landlady, 1847) to Smerdyakov (The brothers Karamazov, 1879-1880),
      Dostoevsky portrayed up to six characters with epilepsy in his literature. Apart
      from making an intelligent use of the disease by incorporating it into his
      novels, his seminal idea -that a moment of happiness is worth a lifetime- was
      probably inspired by his epileptic aura. Through epilepsy, Dostoevsky also found
      a way to freedom from perpetual military servitude. The first symptoms of the
      epilepsy presented in early adulthood (late 1830s to early 1840s), but he was
      only diagnosed a decade later. In 1863 he went abroad seeking expert advice from
      Romberg and Trousseau. In the first retrospective study of Dostoevsky's literary
      epilepsy, Stephenson and Isotoff noticed the influence of Carus' Psyche (1848) in
      the preparation of his characters, whilst his epilepsy has inspired later
      generations of epileptologists. CONCLUSIONS: Dostoevsky offers an insight into
      the natural history of an epilepsy, which in contemporary scientific terms would
      be classified as cryptogenic localization-related of probable temporal lobe
      origin. Above all, Dostoevsky's case illustrates the good use of a common
      neurological disorder by a remarkable writer who transformed suffering into art
      and a disadvantage into an advantage.

PMID- 21893369
TI  - [Rolandic epilepsy clinical variants and their influence on the prognosis].
AB  - INTRODUCTION: Benign epilepsy with central-temporal spikes (BECTS) is the most
      common epileptic syndrome in childhood. It is an age-dependent, genetically
      determined and benign condition. The aim of this study is to describe the
      clinical course and prognosis in 60 patients with BECTS diagnosed in our
      hospital. PATIENTS AND METHODS: We made a retrospective review of patients
      diagnosed with BECTS in a University Hospital (1995-2009). They were divided into
      2 groups: 1) Patients who met all BECTS classical criteria. 2) Patients who met
      all the criteria but one (less than 4 years; diurnal seizures; atypical EEG
      abnormalities). RESULTS: A total of 60 patients, 34 males and 26 females were
      included, with 31 patients in group 1 and 29 in group 2. The mean age at onset in
      group 1: 7.45 years, group 2: 6.55 years. Medical treatment was indicated in
      32.2% of patients in group 1 and 41.3% in group 2. The outcome was favourable in
      the majority: 58% in group 1 and 62.1% in group 2 were free of seizures after 1
      year. Average age in which it disappeared: 8.54 years in group 1 and 7.84 years
      in group 2. There were no statistically significant differences in any of these
      parameters. CONCLUSIONS: Unlike that published by some authors, we have not
      identified any poor outcome factors in patients with BECTS in this study, meaning
      that an accurate diagnosis correlates with a good prognosis and excellent
      neurological outcome.

PMID- 21893370
TI  - [Clinical usefulness of the Spanish version of the Mississippi Aphasia Screening
      Test (MASTsp): validation in stroke patients].
AB  - OBJECTIVE: Clinical validation of the Spanish version of the Mississippi Aphasia
      Screening Test (MASTsp) as a screening test for language disorders in patients
      who have suffered a stroke. MATERIAL AND METHODS: A total of 29 patients who had
      suffered a stroke and had aphasia after a left hemispheric lesion were evaluated
      with the MASTsp, the Boston Diagnostic Aphasia Examination and the Token Test at
      baseline and after six months of rehabilitation. Two expert speech-therapists
      evaluated twelve aphasic patients to determine the inter-observer reliability.
      This sample was assessed twice in the same week to analyse the reproducibility of
      the test (test-retest reliability). Aphasic patients were compared with a matched
      sample of non-aphasic patients with vascular lesions in the right hemisphere (n
      =29) and a group of healthy subjects (n=60) stratified by age and educational
      level. RESULTS: The MASTsp showed a good convergent validity, interobserver
      validity, test-retest reliability and a moderate sensitivity to detect changes
      over time. A diagnostic cut-off <90 on the MASTsp total test score is proposed.
      CONCLUSIONS: The MASTsp is a valid tool for the detection and monitoring of
      language problems in patients with stroke.

PMID- 21893372
TI  - Increased systemic side effects of prostaglandin analogue eye drops in patients
      with palatal defects.

PMID- 21893371
TI  - Synthesis and SAR optimization of diketo acid pharmacophore for HCV NS5B
      polymerase inhibition.
AB  - Hepatitis C virus (HCV) NS5B polymerase is a key target for anti-HCV therapeutics
      development. Here we report the synthesis and biological evaluation of a new
      series of alpha,gamma-diketo acids (DKAs) as NS5B polymerase inhibitors. We
      initiated structure-activity relationship (SAR) optimization around the furan
      moiety of compound 1a [IC(50) = 21.8 MUM] to achieve more active NS5B inhibitors.
      This yielded compound 3a [IC(50) = 8.2 MUM] bearing the 5-bromobenzofuran-2-yl
      moiety, the first promising lead compound of the series. Varying the furan moiety
      with thiophene, thiazole and indazole moieties resulted in compound 11a [IC(50) =
      7.5 MUM] bearing 3-methylthiophen-2-yl moiety. Finally replacement of the
      thiophene ring with a bioisosteric phenyl ring further improved the inhibitory
      activity as seen in compounds 21a [IC(50) = 5.2 MUM] and 24a [IC(50) = 2.4 MUM].
      Binding mode of compound 24a using glide docking within the active site of NS5B
      polymerase will form the basis for future SAR optimization.

PMID- 21893373
TI  - Uptake and translocation of arsenite by Pteris vittata L.: effects of glycerol,
      antimonite and silver.
AB  - AsIII uptake in living cells is through aquaglyceroporin transporters, but it is
      unknown in arsenic-hyperaccumulator Pteris vittata. We investigated the effects
      of AsIII analogs glycerol and antimonite (SbIII) at 0-100 mM and aquaporin
      inhibitor AgNO(3) at 0-0.1 mM on the uptake of 0.1 mM AsIII or AsV by P. vittata
      over 1-2 h. Glycerol or SbIII didn't impact AsIII or AsV uptake by P. vittata (p
      < 0.05), with As concentrations in the fronds and roots being 4.4-6.3 and 3.9-6.2
      mg/kg. However, 0.01 mM AgNO(3) reduced As concentrations in the fronds and roots
      by 64% and 58%. Hence, AsIII uptake in P. vittata might be via an aquaporin
      transporter different from glycerol and SbIII transporters. Further as AsIII
      analogs and aquaporin inhibitor had no impact on AsV uptake, AsIII and AsV were
      likely taken up by different transporters in P. vittata. Our results imply a
      different AsIII transporter in P. vittata from other plants.

PMID- 21893374
TI  - Deserving to a point: unauthorized immigrants in San Francisco's universal access
      healthcare model.
AB  - In the "decidedly hostile" federal context toward unauthorized immigrants in
      American healthcare (Newton & Adams, 2009, p. 422), a few subnational governments
      have implemented strategies seeking to expand their access to and utilization of
      care. In this article, I draw on interviews conducted with 36 primary care
      providers working in San Francisco's public safety net between May and September
      2009 to examine how such inclusive local policies work. On one hand, San
      Francisco's inclusive local policy climate both encourages and reinforces public
      safety-net providers' views of unauthorized immigrants as patients morally
      deserving of equal care, and helps them to translate their inclusive views into
      actual behaviors by providing them with increased financial resources. On the
      other hand, both hidden and formal barriers to care remain in place, which limits
      public safety-net providers' abilities to extend equal care to unauthorized
      immigrants even within this purportedly inclusive local policy context. I discuss
      the implications of the San Francisco case for policymakers, providers, and
      immigrants elsewhere.

PMID- 21893375
TI  - Uncertainty in medicine: meanings of menopause and hormone replacement therapy in
      medical textbooks.
AB  - Menopause is understood, portrayed, and experienced in diverse ways. The dominant
      biomedical perspective medicalizes menopause as a biological 'hormone deficiency'
      requiring 'treatment' with hormone replacement therapy (HRT). Alternative
      perspectives view menopause as discursively located within particular socio
      historical times and places, or privilege women's embodied experiences of
      menopause. We argue that the meanings of menopause and HRT should be debated
      within a context where the biological and the social, or the body and culture,
      intersect. The present study examined international medical student textbooks as
      sites of current biomedical knowledge, communicated for a new generation of
      health professionals. We undertook a Foucauldian discourse analysis on eight
      widely-used, international medical textbooks across physiology, pathology and
      pharmacology subject areas to identify the ways in which menopause and HRT are
      portrayed. Our results showed that menopause continues to be represented through
      dominant culturally infused 'failure' discourses and is portrayed as a 'precursor
      to disease' with HRT as the treatment. However, this knowledge is somewhat
      destabilized by a discourse of 'uncertainty and speculation' regarding the
      physiology of menopause and the potential effects of HRT. Knowledge about
      menopause, osteoporosis, and HRT was constructed as tentative, but the 'quest'
      for new knowledge was constructed as on the verge of 'exciting discoveries'. We
      argue that bio-social understandings of menopause and HRT, and their medical
      uncertainties, need to be addressed in medical curricula to ensure that doctors
      engage with midlife women in appropriate and positive ways, especially given the
      increased call for women's involvement in decision-making at this time.

PMID- 21893376
TI  - Racial and ethnic disparities in hospital care resulting from air pollution in
      excess of federal standards.
AB  - This study investigates racial and ethnic disparities in hospital admission and
      emergency room visit rates resulting from exposure to ozone and fine particulate
      matter levels in excess of federal standards ("excess attributable risk"). We
      generate zip code-level ambient pollution exposures and hospital event rates
      using state datasets, and use pollution impact estimates in the epidemiological
      literature to calculate excess attributable risk for racial/ethnic groups in
      California over 2005-2007. We find that black residents experienced roughly 2.5
      times the excess attributable risk of white residents. Hispanic residents were
      exposed to the highest levels of pollution, but experienced similar excess
      attributable risk to whites. Asian/Pacific Islander residents had substantially
      lower excess attributable risk compared to white. We estimate the distinct
      contributions of exposure and other factors to these results, and find that
      factors other than exposure can be critical determinants of pollution-related
      disparities.

PMID- 21893377
TI  - Public, private, neither, both? Publicness theory and the analysis of healthcare
      organisations.
AB  - In England recent health reforms have resulted in a shift of emphasis from
      targets to outcomes, and to the provision of healthcare by any willing provider.
      The outcomes described encompass clinical and public service outcomes such as
      choice and access. The range of organisations providing healthcare services is
      large and increasing. Whilst many are clearly located in either the public or
      private sectors, others have features of both public and private organisations,
      and are not easily characterised as either one or the other. Analytical
      frameworks are generally underdeveloped, and have not kept pace with changes in
      organisation forms. This article reviews how public and private organisations
      have been compared in organisation theory, describes previous work on dimensional
      publicness in both non-healthcare and healthcare organisations, and presents a
      publicness grid for hospitals in England. Publicness is defined as a
      characteristic of an organisation which reflects the extent to which the
      organisation is influenced by political authority. In establishing a link between
      publicness and public service outcomes it is suggested that core publicness,
      dimensional publicness (consisting of political and economic authority) and
      normative publicness (public sector values) all have to be taken into account,
      since all have an impact on these outcomes. A framework is described that can be
      used to map the relationships between public service outcomes and publicness. How
      the framework can be applied in practice to healthcare organisations is described
      through the development of appropriate indicators and measures. Publicness theory
      can help health administrators and researchers understand and better manage
      public service outcomes. Some of the research questions that might be addressed
      using this approach are considered. Further development of the publicness concept
      in healthcare is advocated.

PMID- 21893378
TI  - Are we finally on the right track in treating "difficult" erectile dysfunction
      patients?

PMID- 21893379
TI  - Local mild hypothermia with thrombolysis for acute ischemic stroke within a 6-h
      window.
AB  - OBJECTIVE: To determine the safety and efficacy of combined local mild
      hypothermia and IV rtPA in treating acute ischemic stroke (AIS) patients with MRI
      perfusion- and diffusion-weighted imaging (PWI/DWI) mismatch within a 6-h stroke
      window. METHODS: AIS patients within 6 h of a minimum 20% PWI/DWI MRI mismatch
      were randomly assigned to 3 groups: local mild hypothermia with IV rtPA (Group
      A); IV rtPA (Group B); or conventional anti-platelet aggregation (Group C).
      Mortality and National Institutes of Health Stroke Scale (NIHSS) and the modified
      Rankin Scale (mRS) score and Barthel Index (BI) were used in evaluation. RESULTS:
      There were significant differences in NIHSS 24 h after treatment among the three
      groups (P<0.001). Based on mRS and BI, more patients in Groups A and B showed
      favorable outcomes than patients in Group C (P=0.017 and P=0.009, respectively);
      however, there were no significant efficacy differences between Groups A and B.
      The incidence of symptomatic ICH and the mortality rates within 90 days in the 3
      groups were similar. In addition, there were no significant differences in NIHSS
      improvement at 24 h and favorable outcomes 90 days after IV rtPA treatment
      between patients within 3 h and 3-6 h from symptom onset. CONCLUSIONS: There was
      no benefit of combined local hypothermia/IV rtPA treatment compared to IV rtPA
      alone. PWI/DWI mismatching on MRI can be a selection criteria for IV rtPA
      treatment within a 6-h window.

PMID- 21893380
TI  - Propagation of herpes simplex virus via pontine fiber in a case of brainstem
      encephalitis.

PMID- 21893381
TI  - Endostar enhances the antineoplastic effects of combretastatin A4 phosphate in an
      osteosarcoma xenograft.
AB  - Vascular-targeting agents (VTAs) can be divided into two groups: anti
      angiogenesis agents and vascular disrupting agents (VDAs). The purpose of this
      study was to evaluate the antineoplastic activity of a combination of the anti
      angiogenesis agent, Endostar, and the VDA combretastatin, A4 phosphate (CA4P).
      This study is the first to evaluate the activity of this combination against
      tumors and the first to investigate the activity of the combination against
      osteosarcoma. Endostar combined with CA4P had a good anti-tumor effect with no
      significant toxicity, and was at least not inferior to adriamycin, which is the
      main drug for osteosarcoma. The use of VDAs combined with anti-angiogenic drugs
      can result in significantly enhanced anti-tumor effects, providing a novel
      approach to cancer treatment, which could effectively complement standard
      treatments. It is believed that this exciting new treatment has the potential to
      transform the management of cancer.

PMID- 21893382
TI  - Establishment of a mammary carcinoma cell line from Syrian hamsters treated with
      N-methyl-N-nitrosourea.
AB  - Clearly new breast cancer models are necessary in developing novel therapies. To
      address this challenge, we examined mammary tumor formation in the Syrian hamster
      using the chemical carcinogen N-methyl-N-nitrosourea (MNU). A single 50mg/kg
      intraperitoneal dose of MNU resulted in a 60% incidence of premalignant mammary
      lesions, and a 20% incidence of mammary adenocarcinomas. Two cell lines, HMAM4A
      and HMAM4B, were derived from one of the primary mammary tumors induced by MNU.
      The morphology of the primary tumor was similar to a high-grade poorly
      differentiated adenocarcinoma in human breast cancer. The primary tumor stained
      positively for both HER-2/neu and pancytokeratin, and negatively for both
      cytokeratin 5/6 and p63. When the HMAM4B cell line was implanted subcutaneously
      into syngeneic female hamsters, tumors grew at a take rate of 50%. A tumor
      derived from HMAM4B cells implanted into a syngeneic hamster was further
      propagated in vitro as a stable cell line HMAM5. The HMAM5 cells grew in female
      syngeneic hamsters with a 70% take rate of tumor formation. These cells
      proliferate in vitro, form colonies in soft agar, and are aneuploid with a modal
      chromosomal number of 74 (the normal chromosome number for Syrian hamster is 44).
      To determine responsiveness to the estrogen receptor (ER), a cell proliferation
      assay was examined using increasing concentrations of tamoxifen. Both HMAM5 and
      human MCF-7 (ER positive) cells showed a similar decrease at 24h. However, MDA-MB
      231 (ER negative) cells were relatively insensitive to any decrease in
      proliferation from tamoxifen treatment. These results suggest that the HMAM5 cell
      line was likely derived from a luminal B subtype of mammary tumor. These results
      also represent characterization of the first mammary tumor cell line available
      from the Syrian hamster. The HMAM5 cell line is likely to be useful as an
      immunocompetent model for human breast cancer in developing novel therapies.

PMID- 21893383
TI  - Exploration of target genes of HOXA13 in esophageal squamous cell carcinoma cell
      line.
AB  - Homeobox genes encode transcriptional factors which regulate cell proliferation
      and differentiation and have been found to be deregulated in many tumors.
      Previously, we found that the median survival time of patients with ESCC
      (Esophageal squamous cell carcinoma) expressing HOXA13 was significantly shorter
      than those with HOXA13-negative ESCC and we also demonstrated that knockdown of
      HOXA13 blocked cell proliferation in vitro and in vivo. In this study, we
      examined the protein expression changes after HOXA13 knockdown by 2-dimentional
      electrophoresis. Forty-five spots were significantly different, among which 24
      were down-regulated and 21 were up-regulated after HOXA13 knockdown. The proteins
      from 14 gel-spots were further characterized by MALDI-TOF MS, among which,
      AnnexinA2, MnSOD and ERAB, are validated by Western Blot analysis.
      Transcriptional target analysis revealed that HOXA13 regulated several cell
      signaling pathways that are critically involved in cell proliferation, survival
      and migration. These results provide an additional support to a hypothesis that
      HOXA13 might participate in the carcinogenesis of ESCC.

PMID- 21893384
TI  - Co-treatment of converter slag and pyrrhotite tailings via high pressure
      oxidative leaching.
AB  - High pressure oxidative acid leaching (HPOXAL) was successfully applied to slow
      cooled converter slags from Vale's operations in Sudbury (Ontario, Canada).
      Extractions of Ni, Co and Cu exceeded 90% within 15-20 min and levelled at 95-97%
      after 45 min at 250 degrees C, 90 psi O(2) overpressure and 70 g/L initial
      H(2)SO(4). Pyrrhotite tailings with ~ 0.6% Ni content were also tested as a
      source of sulphuric acid in high pressure oxidation. Co-leaching of pyrrhotite
      tailings with converter slags at the same temperature, oxygen partial pressure
      and equivalent stoichiometric H(2)SO(4) was found to have kinetics similar to
      that of leaching with sulphuric acid. Lowering the addition of pyrrhotite
      tailings (and hence, the acidity) was found to have a detrimental effect on the
      kinetics of leaching and final extractions (especially at 250 degrees C), and
      cause precipitation of metal sulphates. Continuous on-line acidity measurements
      were facilitated in experiments with an electrodeless conductivity sensor. It was
      shown that acid plays a major role in the conversion of fayalite to hematite and
      silica, and the dissolution of the base metals, while oxygen overpressure (or
      dispersion efficiency) determines the rate of acid generation and re-generation.

PMID- 21893385
TI  - Alpha thalassemia major--a hematological prelude to an oncological problem.
AB  - Alpha thalassemia major and choriocarcinoma are two poles apart clinical
      entities. While the former represents an autosomal recessive disorder of
      hemoglobin synthesis, the later constitutes an aggressive malignant tumor usually
      of placental origin with predilection for women above 35 years, and those with
      history of hydatidiform mole and previous spontaneous abortion. Surprisingly,
      these two entities share strikingly similar geographic distribution. Although
      dietary deficiency esp of carotene and animal fat, and difference in methodology
      of study has been blamed for high occurrence of choriocarcinoma in Asia region, a
      very plausible explanation may be the high rate of spontaneous abortion in this
      region secondary to high incidence of alpha thalassemia major. While it is
      worthwhile investigating the factors that increases the risk of choriocarcinoma
      on account of its high prevalence in Southeast Asia, understanding the
      influential role of alpha thalassemia in its strikingly higher occurrence will
      definitely aid in further reducing its incidence to a minimum.

PMID- 21893386
TI  - Similar hyporesponsiveness of the dorsomedial prefrontal cortex in problem
      gamblers and heavy smokers during an inhibitory control task.
AB  - BACKGROUND: Behavioral addictions like pathological gambling share many clinical
      characteristics with substance dependence. In addition, both types of disorders
      are associated with impairments in inhibitory control. Studies in patients with
      substance use disorders point to hyporesponsiveness of the dorsomedial prefrontal
      cortex. However, no such data exist on behavioral addictions. METHODS: Using
      functional magnetic resonance imaging, we investigated the neural circuitry
      associated with impaired response inhibition in a group of male problem gamblers
      (n=17) using a stop signal task. We included control conditions tailored to
      specifically isolate neural correlates of inhibitory control. To investigate the
      specificity of effects, a group of heavy smokers (n=18) and a group of healthy
      controls (n=17) were also included. RESULTS: Groups did not differ in behavioral
      performance on the stop signal task. However, both problem gamblers and heavy
      smokers showed hyporesponsiveness of the dorsomedial prefrontal cortex compared
      to healthy controls, during successful as well as failed response inhibition.
      These effects were robust against adjustments for depression and adult attention
      deficit scores. CONCLUSIONS: These findings suggest that hypoactivation of the
      inhibition circuit is a shared neural mechanism in substance use disorders and
      behavioral addictions. As such, they support the reclassification of pathological
      gambling as a behavioral addiction in DSM-V.

PMID- 21893387
TI  - Mutant prevention concentration and phenotypic and molecular basis of
      fluoroquinolone resistance in clinical isolates and in vitro-selected mutants of
      Escherichia coli from dogs.
AB  - The antibacterial activity, selection of Escherichia coli (E. coli) mutants and
      mechanisms of fluoroquinolone resistance were investigated by integrating the
      minimum inhibitory concentration (MIC), mutant prevention concentration (MPC) and
      in vitro dynamic model approaches. Difloxacin and orbifloxacin, for which the
      above information has been scarce, were used. A range of area under curve over a
      24h interval (AUC(24h))/MIC ratios and selected E. coli strains were investigated
      using the dynamic models. Continuous incubation for three days in the presence of
      difloxacin or orbifloxacin resulted in losses in E. coli susceptibility. An
      AUC(24h)/MIC (AUC(24h)/MPC)-dependent fluoroquinolone activity and selection of
      E. coli mutants was confirmed. Maximum losses in susceptibility occurred at
      AUC(24h)/MIC ratios of 54 (orbifloxacin) and 57.3 (difloxacin). AUC(24h)/MIC
      ratios of 169.8 (orbifloxacin) and 199.5 (difloxacin) were estimated to be
      protective against the selection of E. coli mutants, and the corresponding ratios
      based on AUC(24h)/MPC predictions were 34 (orbifloxacin) and 36.3 (difloxacin).
      When integrating our in vitro data with pharmacokinetic data in dogs, the
      conventional clinical doses of both drugs were found to be inadequate to attain
      the above protective values for 90% of the mutant subpopulation
      (AUC(24h)/MPC(90)). Both target mutations, esp. at codon 83 (Ser to Leu) of gyrA,
      and overexpression of efflux pumps contributed to resistance development, with
      mutants also showing decreased susceptibility to enrofloxacin and marbofloxacin.
      Additional studies would determine the role of mutations found outside the QRDR,
      at codon 24 of gyrA, and at codon 116 of parC, and establish the significance of
      these observations in vivo.

PMID- 21893388
TI  - Quality of life and health status after prophylactic salpingo-oophorectomy in
      women who carry a BRCA mutation: A review.
AB  - Prophylactic salpingo-oophorectomy is recommended to women who carry a BRCA1 or
      BRCA2 mutation at age 35 or after childbearing is complete. This procedure is the
      mainstay of ovarian and fallopian tube cancer prevention in these women.
      Therefore an understanding of the short and long-term impact of the surgery is
      essential. Salpingo-oophorectomy, particularly when done prior to natural
      menopause, may impact on several aspects of quality of life and health. The
      health benefits of this surgery (cancer prevention) should outweigh the costs of
      the procedure in terms of quality of life and long term health. In this review,
      the impact of this surgery on quality of life and health in women who carry a
      BRCA mutation is discussed. Preliminary studies have focused on short-term
      effects, such as quality of life. In the short term, overall quality of life
      appears to be similar before and after surgery, however vasomotor symptoms
      related to surgical menopause and changes in sexual functioning are common. HRT
      appears to mitigate some but not all of these symptoms. Women report high levels
      of satisfaction with their decision to have the surgery despite the impact of
      prophylactic salpingo-oophorectomy. Studies of the long term health and quality
      of life after salpingo-oophorectomy in women who carry a BRCA mutation have not
      yet been published.

PMID- 21893389
TI  - Novel V97G ASAH1 mutation found in Farber disease patients: unique appearance of
      the disease with an intermediate severity, and marked early involvement of
      central and peripheral nervous system.
AB  - Farber disease is a rare inherited lysosomal storage disorder caused by
      ceramidase deficiency that leads to accumulation of ceramide in various tissues.
      Mutations within ASAH1 encoding for acid ceramidase are responsible for the
      disease. Here we report two siblings with Farber disease who carry a novel V97G
      with the parents and a sister being asymptomatic carriers. The mutation site was
      found to be highly conserved among different species using ClustalW2 alignment.
      Functional prediction tools indicated the mutation to be pathogenic. Electron
      microscopy based ultrastructural studies using skin biopsy showed inclusion of
      enlarged lysosomes and presence of the zebra bodies. The T1 weighted magnetic
      resonance images of the brain indicated diffuse loss of the deep white matter
      volume predominantly along the occipital horns of the lateral ventricle with
      subsequent facet dilatation of the supratentorial and infratentorial ventricular
      system. This is the first report of a detailed clinical and molecular analysis of
      cases with Farber disease from Saudi Arabia.

PMID- 21893390
TI  - Long-term effectiveness of ethosuximide, valproic acid, and lamotrigine in
      childhood absence epilepsy.
AB  - PURPOSE: We performed this study to evaluate the long-term efficacy and
      tolerability of ethosuximide (ESX), valproic acid (VPA), and lamotrigine (LTG) as
      initial monotherapies for patients with newly diagnosed childhood absence
      epilepsy. METHODS: We retrospectively reviewed the medical records of 128
      patients (45 boys and 83 girls) diagnosed with childhood absence epilepsy at the
      Seoul National University Hospital. The diagnosis was based on the criteria
      proposed by Panayiotopoulos in 2005. We measured the seizure-free rate and the
      retention rate observed during 2 years of treatment. Follow-up
      electroencephalography (EEG), any reported adverse events, and reasons for
      antiepileptic drug (AED) discontinuation were reviewed. RESULTS: The seizure-free
      rate of ESX (84%) was significantly higher than that of VPA (62%) and LTG (53%)
      at 3 months. The seizure-free rate of ESX (90%) was significantly higher than
      that of LTG (63%) at 6 months. After 9 months, there was no significant
      difference in seizure-free rate among the three groups. There were no significant
      differences among the three groups in terms of normalization of EEG at 12 months
      (ESX, 77%; VPA, 83%; and LTG, 64%), retention rate throughout the whole treatment
      period, and adverse-event rates (ESX, 25%; VPA, 29%; and LTG, 14%). CONCLUSION:
      This study suggests that ESX, VPA, and LTG are equally effective in the long-term
      treatment of newly diagnosed CAE patients. However, the onset of efficacy was
      faster for ESX compared with VPA or LTG. Efficacy, tolerability, and adverse
      event profiles should be carefully considered when selecting AEDs to treat
      individual patients with CAE.

PMID- 21893391
TI  - Review of MRI technique and imaging findings in athletic pubalgia and the "sports
      hernia".
AB  - The clinical syndrome of athletic pubalgia has prematurely ended many promising
      athletic careers, has made many active, fitness conscious adults more sedentary,
      and has served as a diagnostic and therapeutic conundrum for innumerable trainers
      and physicians worldwide for decades. This diagnosis actually arises from one or
      more lesions within a spectrum of musculoskeletal and visceral injuries. In
      recent years, MRI has helped define many of these syndromes, and has proven to be
      both sensitive and specific for numerous potential causes of athletic pubalgia.
      This text will provide a comprehensive, up to date review of expected and
      sometimes unexpected MRI findings in the setting of athletic pubalgia, and will
      delineate an imaging algorithm and MRI protocol to help guide radiologists and
      other clinicians dealing with refractory, activity related groin pain in an
      otherwise young, healthy patient. There is still more to be learned about
      prevention and treatment plans for athletic pubalgia lesions, but accurate
      diagnosis should be much less nebulous and difficult with the use of MRI as a
      primary imaging modality.

PMID- 21893392
TI  - Hip pain from the orthopeadic point of view.
AB  - The hip and its disorders represent a clinical, diagnostic and therapeutic
      challenge greater than any other joints. Clinical symptoms are usually non
      specific and provocative maneuvers are sometimes unreliable, pain might be
      referred even from other joints and many times accurate assessment need imaging
      techniques. New surgical options, especially the latest development of hip
      arthroscopy has open horizons for treating intraarticular disorders. In this
      review article we will review basic clinical assessment and what we need as
      orthopeadic surgeons from radiology.

PMID- 21893393
TI  - Comparative pharmacokinetics of three marker compounds in mBHT and single-herb
      extract after oral administration to rats.
AB  - Modified Bo-Yang-Hwan-O-Tang (mBHT) is a decoction of 12 herbs traditionally used
      in the treatment of cerebral and cardiac stroke and vascular dementia.
      Paeoniflorin (PF), calycosin-7-O-beta-D-glycoside (CY), and salvianolic acid B
      (SB) are marker compounds for extracts of the herbs Paeoniae Radix, Astragali
      Radix, and Salviae Miltiorrhizae Radix, respectively, and are used to assess the
      quality of mBHT. This study examined the pharmacokinetics of these three marker
      compounds following oral administration of each herb extract alone and in
      combination as mBHT in rats. The concentrations of the three compounds in rat
      plasma were determined by high-performance liquid chromatography, using a C18
      column (2.1*150 mm, 5 MUm) and mobile phases of methanol-water-formic acid
      (10:90:0.05, v/v) and methanol-water (90:10, v/v). The results indicated that the
      pharmacokinetic parameters of Paeoniae Radix extract group and mBHT group were
      very similar, while those of Salviae Miltiorrhizae Radix extract group and mBHT
      group were significantly different (P<0.05, t-test). The T(max), AUC and T(1/2)
      of SB for Salviae Miltiorrhizae Radix extract group were 54.7 min, 598.7 MUg
      min/ml and 37.4 min, respectively. However, these values increased to 77.6 min,
      915.9 MUg min/ml and 53.7 min for mBHT group, supposing that excretion of SB
      could be more retarded when administered in mBHT than in Salviae Miltiorrhizae
      Radix extract.

PMID- 21893394
TI  - Expanding the term "Design Space" in high performance liquid chromatography (I).
AB  - The current article presents a novel approach to applying Quality by Design (QbD)
      principles to the development of high pressure reversed phase liquid
      chromatography (HPLC) methods. Four common critical parameters in HPLC--gradient
      time, temperature, pH of the aqueous eluent, and stationary phase--are evaluated
      within the Quality by Design framework by the means of computer modeling software
      and a column database, to a satisfactory degree. This work proposes the
      establishment of two mutually complimentary Design Spaces to fully depict a
      chromatographic method; one Column Design Space (CDS) and one Eluent Design Space
      (EDS) to describe the influence of the stationary phase and of the mobile phase
      on the separation selectivity, respectively. The merge of both Design Spaces into
      one is founded on the continuous nature of the mobile phase influence on
      retention and the great variety of the stationary phases available.

PMID- 21893395
TI  - Initial experiences with a multidisciplinary approach to decreasing the length of
      hospital stay for patients undergoing unilateral mastectomy.
AB  - BACKGROUND: We hypothesized that the introduction of a short-stay pathway would
      result in a significant reduction in length of stay for patients undergoing
      unilateral mastectomy, without a negative impact on patient safety. MATERIALS AND
      METHODS: As part of a quality improvement project, a multidisciplinary committee
      designed a 1-day stay program for unilateral mastectomy patients. The study
      period was the first year after the 1-day pathway had routinely been implemented.
      We report on consecutive patients undergoing unilateral mastectomy +/- tissue
      expander at Memorial Sloan-Kettering Cancer Center from July 1, 2009 to June 30,
      2010. The primary endpoint was the percentage of patients discharged on
      postoperative day 1. Secondary endpoints included the incidence of postoperative
      complications within 30 days of surgery, reoperations, readmissions, and urgent
      care visits within 7 days. RESULTS: Over a 12-month period, 537 patients
      underwent unilateral mastectomy. Of those, 82.7% (444/537) were performed on a 1
      day hospitalization basis, compared with 9.6% in 2008, before implementation of
      the 1-day plan. The 30-day complication rate was 6.1% (33/537). Overall, 2.6% of
      all patients had reoperation for hematoma (14/537), 0.9% had to be readmitted
      (5/537), and 1.5% (8/537) attended the urgent-care department. If all patients
      had stayed in the hospital for more than 1 day, none of the readmissions and only
      2 urgent-care visits would have been prevented. CONCLUSIONS: This study shows
      that a 1-day stay following mastectomy is easy to implement and safe for patients
      if a multidisciplinary team is involved in planning and implementation.

PMID- 21893396
TI  - Pingyangmycin sclerotherapy for infantile hemangiomas in oral and maxillofacial
      regions: an evaluation of 66 consecutive patients.
AB  - The management of infantile hemangiomas remains a subject of controversy. The
      purpose of this study was to investigate the indications and treatment results of
      intralesional injection of pingyangmycin for treatment of infantile hemangiomas.
      In a prospective study of 66 patients, the effectiveness of intralesional
      injection of pingyangmycin was evaluated and documented. The lesions were all
      located in the oral and maxillofacial regions. The smallest lesion was 1.0 cm *
      0.7 cm and the largest was 4.6 cm * 3.8 cm. Amongst the 66 infants who underwent
      sclerotherapy with pingyangmycin, cure was obtained in 74% (49/66) of patients,
      marked improvement of the treated lesion occurred in 14% (9/66), improvement
      occurred in 12% (8/66), and a lack of response was not observed in any patient.
      All patients were regularly followed up for 1-4 years following pingyangmycin
      treatment, and they demonstrated the same good results over this time.
      Intralesional injection of pingyangmycin was a reliable and effective therapeutic
      choice for infantile oral and maxillofacial hemangiomas, as it shortened the
      involution time and decreased the influence induced by these potentially
      countenance-influenced tumours with few complications.

PMID- 21893397
TI  - Extracellular proteases in epilepsy.
AB  - During the last decade, multiple data have been obtained, pointing to an
      involvement of extracellular, including extrasynaptic, proteolysis in epilepsy
      pathogenesis. The most productive avenues of investigations have been analyses of
      seizure-evoked gene and protein expression patterns, both hypothesis-driven and
      unbiased (e.g., DNA microarrays), complemented by functional analyses in animal
      models, as well as expression and gene polymorphism studies carried out on human
      tissue In result, serine proteases (e.g., tPA, thrombin, trypsin-like proteases,
      etc.), metalloproteinases, natural protease inhibitors, as well as complement
      components, and reelin have been identified as a novel molecular system, emerging
      as a key factor in the development of epilepsy, in addition to well known
      contribution of ion channels and signal transduction pathways. The extracellular
      location of the enzymes makes them particularly attractive potential targets for
      future pharmacological therapeutic interventions.

PMID- 21893398
TI  - Selective electrooxidation of uric acid in presence of ascorbic acid at a room
      temperature ionic liquid/nickel hexacyanoferarrate nanoparticles composite
      electrode.
AB  - A novel amperometric sensor for the determination of uric acid was fabricated
      using room temperature ionic liquid and nickel hexacyanoferrate nanoparticle
      composite which was immobilized on paraffin wax impregnated graphite electrode.
      The nickel hexacyanoferrate nanoparticle was characterized by UV-vis, X-ray
      diffraction and field emission scanning electron microscopy. The electrochemical
      behavior of the modified electrode was investigated in detail by electrochemical
      impedance spectroscopy, cyclic voltammetry and differential pulse voltammetry.
      Various experimental parameters influencing the electrochemical behavior of the
      modified electrode were optimized by varying the supporting electrolyte, scan
      rate and pH. The apparent electron transfer rate constant (K(s)) and charge
      transfer coefficient (alpha) of the modified electrode were found to be 1.358(+/-
      0.02)cm/s and 0.65, respectively from cyclic voltammetry. The sensor exhibited an
      excellent electrocatalytic activity towards the oxidation of uric acid. The
      interference from ascorbic acid was easily overcome by coating the modified
      electrode with PEDOT layer. Under optimal condition, the determination range for
      uric acid is from 1.0 * 10(-6)M to 2.6 * 10(-3)M and the detection limit was 3.3
      * 10(-7)M (3sigma). The proposed method has been used for the determination of
      uric acid in human urine samples.

PMID- 21893399
TI  - Submicroparticles composed of amphiphilic chitosan derivative for oral insulin
      and curcumin release applications.
AB  - Amphiphilic polymers for dual drug delivery have been a focus of research in
      recent years. We have previously developed and characterized Lauroyl sulphated
      chitosan (LSCS). Here biological characterizations like mucoadhesion,
      cytotoxicity, calcium binding, tight junction opening and enzymatic degradation
      studies were performed to understand its applicability. In vitro drug release
      properties of both hydrophilic insulin and hydrophobic curcumin were carried out.
      The biological activity and stability of released insulin were also studied. The
      stability studies of encapsulated curcumin and uptake studies have also been
      carried out. LSCS showed strong mucoadhesion and 100% of non-toxicity. LSCS could
      transiently open tight junctions between Caco-2 cells and thus increase the
      paracellular permeability. LSCS enhanced calcium binding properties and decreased
      enzymatic degradation rate retaining insulin activity. LSCS could protect
      curcumin from photodegradation and could also enter into the cells. From release
      studies, LSCS was found to be a suitable candidate for both drugs.

PMID- 21893400
TI  - Voltammetric behaviour of antimalarial drug artesunate in solubilized systems.
AB  - The voltammetric behaviour of artesunate is studied at glassy carbon electrode in
      different buffer systems using square wave, differential pulse and cyclic
      voltammetric techniques. The peak current is linear with the drug concentration
      in the range 4.0-40 MUg mL(-1) for serum, plasma and urine. The mean percentage
      recoveries of the drug, urine, plasma and serum samples are 98.6-100.2%. No
      electroactive interferences from the excipients and endogenous substance could be
      observed in the pharmaceutical dosage forms and in biological samples.

PMID- 21893401
TI  - Modified Wu-Zi-Yan-Zong prescription, a traditional Chinese polyherbal formula,
      suppresses lipopolysaccharide-induced neuroinflammatory processes in rat
      astrocytes via NF-kappaB and JNK/p38 MAPK signaling pathways.
AB  - Neuroinflammation plays an important role in several neurodegenerative diseases.
      In this study, we investigated the anti-inflammatory properties of modified Wu-Zi
      Yan-Zong prescription (MWP), a traditional Chinese polyherbal formula, in primary
      cultured rat astrocytes treated with lipopolysaccharide (LPS). The results showed
      that MWP significantly inhibited release of nitric oxide (NO) and prostaglandin E
      (PGE), as well as expressions of inducible nitric oxide synthase (iNOS) and
      cyclooxygenase (COX)-2 in LPS-induced rat astrocytes. Mechanism study indicated
      that MWP significantly inhibited nuclear factor-kappa B (NF-kappaB) inflammatory
      signaling pathway through attenuating inhibitor of nuclear factor-kappaB
      (IkappaB) degradation and down-regulating IkappaB kinases (IKKs) phosphorylation
      level. Moreover, MWP also decreased c-Jun NH(2)-terminal kinase (JNK)/p38 mitogen
      activated protein kinase (MAPK) phosphorylation, which play an important role in
      the induction of proinflammatory gene expressions. At last, MWP protected neurons
      from LPS-activated astrocytes in neuron-astrocyte co-culture system. Taken
      together, our results suggest that MWP may act to suppress neuroinflammatory
      response in LPS-stimulated rat astrocytes via NF-kappaB and JNK/p38 MAPK
      signaling cascades, and MWP may be a useful agent for prevention and treatment of
      neuroinflammatory disease.

PMID- 21893402
TI  - In vitro antifungal, anti-elastase and anti-keratinase activity of essential oils
      of Cinnamomum-, Syzygium- and Cymbopogon-species against Aspergillus fumigatus
      and Trichophyton rubrum.
AB  - This study was aimed to evaluate effects of certain essential oils namely
      Cinnamomum verum, Syzygium aromaticum, Cymbopogon citratus, Cymbopogon martini
      and their major components cinnamaldehyde, eugenol, citral and geraniol
      respectively, on growth, hyphal ultrastructure and virulence factors of
      Aspergillus fumigatus and Trichophyton rubrum. The antifungal activity of
      essential oils and their major constituents was in the order of
      cinnamaldehyde>eugenol>geraniol=C. verum>citral>S. aromaticum>C. citratus>C.
      martini, both in liquid and solid media against T. rubrum and A. fumigatus. Based
      on promising antifungal activity of eugenol and cinnamaldehyde, these oils were
      further tested for their inhibitory activity against ungerminated and germinated
      conidia in test fungi. Cinnamaldehyde was found to be more active than eugenol.
      To assess the possible mode of action of cinnamaldehyde, electron microscopic
      studies were conducted. The observations revealed multiple sites of action of
      cinnamaldehyde mainly on cell membranes and endomembranous structures of the
      fungal cell. Further, test oils were also tested for their anti-virulence
      activity. More than 70% reduction in elastase activity was recorded in A.
      fumigatus by the oils of C. verum, C. martini, eugenol, cinnamaldehyde and
      geraniol. Similar reduction in keratinase activity in A. niger was recorded for
      the oils of C. martini and geraniol. Maximum reduction (96.56%) in elastase
      activity was produced by cinnamaldehyde whereas; geraniol caused maximum
      inhibition (97.31%) of keratinase activity. Our findings highlight anti-elastase
      and anti-keratinase activity of above mentioned essential oils as a novel
      property to be exploited in controlling invasive and superficial mycoses.

PMID- 21893403
TI  - Proteomic analysis of the molecular response of Raji cells to maslinic acid
      treatment.
AB  - Maslinic acid, a natural pentacyclic triterpene has been shown to inhibit growth
      and induce apoptosis in some tumour cell lines. We studied the molecular response
      of Raji cells towards maslinic acid treatment. A proteomics approach was employed
      to identify the target proteins. Seventeen differentially expressed proteins
      including those involved in DNA replication, microtubule filament assembly,
      nucleo-cytoplasmic trafficking, cell signaling, energy metabolism and
      cytoskeletal organization were identified by MALDI TOF-TOF MS. The down
      regulation of stathmin, Ran GTPase activating protein-1 (RanBP1), and microtubule
      associated protein RP/EB family member 1 (EB1) were confirmed by Western
      blotting. The study of the effect of maslinic acid on Raji cell cycle regulation
      showed that it induced a G1 cell cycle arrest. The differential proteomic changes
      in maslinic acid-treated Raji cells demonstrated that it also inhibited
      expression of dUTPase and stathmin which are known to induce early S and G2 cell
      cycle arrests. The mechanism of maslinic acid-induced cell cycle arrest may be
      mediated by inhibiting cyclin D1 expression and enhancing the levels of cell
      cycle-dependent kinase (CDK) inhibitor p21 protein. Maslinic acid suppressed
      nuclear factor-kappa B (NF-kappaB) activity which is known to stimulate
      expression of anti-apoptotic and cell cycle regulatory gene products. These
      results suggest that maslinic acid affects multiple signaling molecules and
      inhibits fundamental pathways regulating cell growth and survival in Raji cells.

PMID- 21893404
TI  - A homeopathic remedy for early COPD.

PMID- 21893406
TI  - Fluorescent europium-modified polymer nanoparticles for rapid and sensitive
      anthrax sensors.
AB  - Novel fluorescent polyacrylonitrile nanoparticles were synthesized by
      microemulsion polymerization and Schiff base modification. By further
      modification with europium, the polyacrylonitrile nanoparticles could be used as
      a highly sensitive and rapid sensor for Bacillus anthracis spore detection in
      aqueous solution. The europium-modified polyacrylonitrile nanoparticles were
      readily combined with dipicolinic acid as a unique biomarker of B. anthracis,
      leading to high fluorescence emission. These nanoparticles enabled ratiometric
      detection without instrument-specific calibration due to the internal
      fluorescence reference. Additionally, the europium-modified polyacrylonitrile
      nanoparticle sensors exhibited a remarkable limit of detection (10pM) for
      dipicolinic acid and outstanding selectivity (160*) over aromatic ligands in
      aqueous solution. The ultrafine nanoparticle sensor showed a high capability for
      detecting anthrax due to the increased surface area-to-volume ratio and enhanced
      dispersibility.

PMID- 21893405
TI  - Engineering and optimization of an allosteric biosensor protein for peroxisome
      proliferator-activated receptor gamma ligands.
AB  - The peroxisome proliferator-activated receptor gamma (PPARgamma or PPARG) belongs
      to the nuclear receptor superfamily, and is a potential drug target for a variety
      of diseases. In this work, we constructed a series of bacterial biosensors for
      the identification of functional PPARgamma ligands. These sensors entail modified
      Escherichia coli cells carrying a four-domain fusion protein, comprised of the
      PPARgamma ligand binding domain (LBD), an engineered mini-intein domain, the E.
      coli maltose binding protein (MBD), and a thymidylate synthase (TS) reporter
      enzyme. E. coli cells expressing this protein exhibit hormone ligand-dependent
      growth phenotypes. Unlike our published estrogen (ER) and thyroid receptor (TR)
      biosensors, the canonical PPARgamma biosensor cells displayed pronounced growth
      in the absence of ligand. They were able to distinguish agonists and antagonists,
      however, even in the absence of agonist. To improve ligand sensitivity of this
      sensor, we attempted to engineer and optimize linker peptides flanking the
      PPARgamma LBD insertion point. Truncation of the original linkers led to
      decreased basal growth and significantly enhanced ligand sensitivity of the
      PPARgamma sensor, while substitution of the native linkers with optimized G(4)S
      (Gly-Gly-Gly-Gly-Ser) linkers further increased the sensitivity. Our studies
      demonstrate that the properties of linkers, especially the C-terminal linker,
      greatly influence the efficiency and fidelity of the allosteric signal induced by
      ligand binding. Our work also suggests an approach to increase allosteric
      behavior in this multidomain sensor protein, without modification of the
      functional LBD.

PMID- 21893407
TI  - Quantitative microscopy and imaging tools for the mechanical analysis of
      morphogenesis.
AB  - The importance of mechanical signals during embryogenesis and development,
      through both intercellular and extracellular signals, is coming into focus. It is
      widely hypothesized that physical forces help to guide the shape, cellular
      differentiation and the patterning of tissues. To test these ideas many classical
      engineering principles and imaging technologies are being adapted. Recent
      advances in microscopy, mechanical testing and genetic and pharmacological
      techniques, alongside computational models are helping to dissect the activity of
      mechanical signals in development at the cellular and molecular level. These
      inroads are providing maps of mechanical changes in tissue structure and
      stiffness, and will permit deeper insights into the role of mechanics in both
      developmental biology and disease.

PMID- 21893408
TI  - Imaging heart development using high-resolution episcopic microscopy.
AB  - Development of the heart in vertebrate embryos is a complex process in which the
      organ is continually remodelled as chambers are formed, valves sculpted and
      connections established to the developing vascular system. Investigating the
      genetic programmes driving these changes and the environmental factors that may
      influence them is critical for our understanding of congenital heart disease. A
      recurrent challenge in this work is how to integrate studies as diverse as those
      of cardiac gene function and regulation with an appreciation of the localised
      interactions between cardiac tissues not to mention the manner in which both may
      be affected by cardiac function itself. Meeting this challenge requires an
      accurate way to analyse the changes in 3D morphology of the developing heart,
      which can be swift or protracted and both dramatic or subtle in consequence. Here
      we review the use of high-resolution episcopic microscopy as a simple and
      effective means to examine organ structure and one that allows modern computing
      methods pioneered by clinical imaging to be applied to the embryonic heart.

PMID- 21893409
TI  - Tuning cell shape change with contractile ratchets.
AB  - Throughout the lifespan of an organism, shape changes are necessary for cells to
      carry out their essential functions. Nowhere is this more dramatic than embryonic
      development and gastrulation, when cell shape changes drive large-scale
      rearrangements in tissue architecture to establish the body plan of the organism.
      A longstanding question for both cell and developmental biologists has been how
      are forces generated to change cell shape? Recent studies in both cell culture
      and developing embryos have combined live imaging, computational analysis,
      genetics, and biophysics to identify ratchet-like behaviors in actomyosin
      networks that operate to incrementally change cell shape, drive cell movement,
      and deform tissues. Our analysis of several cell shape changes leads us to
      propose four regulatory modules associated with ratchet-like deformations that
      are tuned to generate diverse cell behaviors, coordinating cell shape change
      across a tissue.

PMID- 21893410
TI  - Image analysis for understanding embryo development: a bridge from microscopy to
      biological insights.
AB  - The digital reconstruction of the embryogenesis of model organisms from 3D+time
      data is revolutionizing practices in quantitative and integrative Developmental
      Biology. A manual and fully supervised image analysis of the massive complex data
      acquired with new microscopy technologies is no longer an option and automated
      image processing methods are required to fully exploit the potential of imaging
      data for biological insights. Current developments and challenges in biological
      image processing include algorithms for microscopy multiview fusion, cell nucleus
      tracking for quasi-perfect lineage reconstruction, segmentation, and validation
      methodologies for cell membrane shape identification, single cell gene expression
      quantification from in situ hybridization data, and multidimensional image
      registration algorithms for the construction of prototypic models. These tools
      will be essential to ultimately produce the multilevel in toto reconstruction
      that combines the cell lineage tree, cells, and tissues structural information
      and quantitative gene expression data in its spatio-temporal context throughout
      development.

PMID- 21893411
TI  - Optimization of butanol production from tropical maize stalk juice by
      fermentation with Clostridium beijerinckii NCIMB 8052.
AB  - Mixed sugars from tropical maize stalk juice were used to carry out butanol
      fermentation with Clostridium beijerinckii NCIMB 8052. Batch experiments
      employing central composite design (CCD) and response surface methodology (RSM)
      optimization were performed to evaluate effects of three factors, i.e. pH,
      initial total sugar concentration, and agitation rate on butanol production.
      Optimum conditions of pH 6.7, sugar concentration 42.2g/L and agitation rate 48
      rpm were predicted, under which a maximum butanol yield of 0.27 g/g-sugar was
      estimated. Further experiments demonstrated that higher agitation facilitated
      acetone production, leading to lower butanol selectivity in total acetone-butanol
      ethanol (ABE). While glucose and fructose are more preferable by C. beijerinckii,
      sucrose can also be easily degraded by the microorganism. This study indicated
      that RSM is a useful approach for optimizing operational conditions for butanol
      production, and demonstrated that tropical maize, with high yield of biomass and
      stalk sugars, is a promising biofuel crop.

PMID- 21893412
TI  - Removal of highly elevated nitrate from drinking water by pH-heterogenized
      heterotrophic denitrification facilitated with ferrous sulfide-based autotrophic
      denitrification.
AB  - The performance of acetic acid-supported pH-heterogenized heterotrophic
      denitrification (HD) facilitated with ferrous sulfide-based autotrophic
      denitrification (AD) was investigated in upflow activated carbon-packed column
      reactors for reliable removal of highly elevated nitrate (42 mg NO(3)-Nl(-1)) in
      drinking water. The use of acetic acid as substrate provided sufficient internal
      carbon dioxide to completely eliminate the need of external pH adjustment for HD,
      but simultaneously created vertically heterogenized pH varying from 4.8 to 7.8 in
      the HD reactor. After 5-week acclimation, the HD reactor developed a moderate
      nitrate removal capacity with about one third of nitrate removal occurring in the
      acidic zone (pH 4.8-6.2). To increase the treatment reliability, acetic acid
      supported HD was operated under 10% carbon limitation to remove >85% of nitrate,
      and ferrous sulfide-based AD was supplementally operated to remove residual
      nitrate and formed nitrite without excess of soluble organic carbon, nitrite or
      sulfate in the final effluent.

PMID- 21893413
TI  - Cellulose extraction from orange peel using sulfite digestion reagents.
AB  - Orange peel (OP) was used as raw material for cellulose extraction. Two different
      pulping reagents were used, sodium sulfite and sodium metabisulfite. The effect
      of the main process parameters, sulfite agent dosage and reaction duration, on
      cellulose yield was investigated. A central composite rotatable design involving
      two variables at five levels and response surface methodology were used for the
      optimization of cellulose recovery. Other two invariable parameters were reaction
      temperature and hydromodulus. The optimum yields, referred to the weight of
      double extracted OP, were 40.4% and 45.2% for sodium sulfite and sodium
      metabisulfite digestions, respectively. The crude celluloses were bleached with
      hypochlorite and oxygen. The physicochemical characterization data of these
      cellulose materials indicate good levels of purity, low crystallinities, good
      whitenesses, good water retention and moderate molecular weights. According to
      these specific properties the recovered celluloses could be used as fillers,
      water absorbents, or as raw materials for cellulose derivatives.

PMID- 21893414
TI  - Non-indigenous microorganisms in the Antarctic: assessing the risks.
AB  - The Antarctic continent is frequently cited as the last pristine continent on
      Earth. However, this view is misleading for several reasons. First, there has
      been a rapid increase in visitors to Antarctica, with large increases at research
      bases and their environs and to sites of major tourist interest (e.g. historical
      sites and concentrations of megafauna). Second, although substantial efforts are
      made to avoid physical disturbance and contamination by chemical, human and other
      wastes at these sites, little has been done to prevent the introduction of non
      indigenous microorganisms. Here, we analyse the extent and significance of
      anthropogenic introduction of microbial 'contaminants' to the Antarctic
      continent. We conclude that such processes are unlikely to have any immediate
      gross impact on microbiological community structure or function, but that
      increased efforts are required to protect the unique ecosystems of Antarctica
      from microbial and genetic contamination and homogenisation.

PMID- 21893415
TI  - Potential AMPK activators of cucurbitane triterpenoids from Siraitia grosvenorii
      Swingle.
AB  - AMP-activated kinase (AMPK) as a key controller in the regulation of whole-body
      energy homeostasis, plays an important role in protecting the body from metabolic
      diseases. Recently, improved glucose, lipid utility and increased insulin
      sensitivity were observed on several diabetic rodent models treated with crude
      mogrosides isolated from the fruit of Siraitia grosvenorii Swingle, but the
      precise active compounds responsible for the anti-diabetic activity of this plant
      have not been clearly identified. In our current work, acid hydrolysis of crude
      mogrosides provided five new cucurbitane triterpenoids (1-4, 8), along with three
      known ones (5-7). The main aglycone mogrol (7) and compounds 4 and 8 were found
      to be potent AMPK activators in the HepG2 cell line. This result suggested AMPK
      activation by the mogroside aglycones 7 and 8 was proved to contribute at least
      partially to the anti-hyperglycemic and anti-lipidemic properties in vivo of S.
      grosvenorii.

PMID- 21893416
TI  - Design and synthesis of inhibitors of noroviruses by scaffold hopping.
AB  - A scaffold hopping strategy was employed to identify new chemotypes that inhibit
      noroviruses. The replacement of the cyclosulfamide scaffold by an array of
      heterocyclic scaffolds lead to the identification of additional series of
      compounds that possessed anti-norovirus activity in a cell-based replicon system.

PMID- 21893417
TI  - Fibrosis of pulmonary vascular remodeling in carotid artery-jugular vein shunt
      pulmonary artery hypertension model of rats.
AB  - OBJECTIVE: The aim of the present study was to observe the changes of
      hemodynamics, stereology in pulmonary vascular remodeling and messenger RNA
      (mRNA) expressions of transforming growth factor beta 1, and receptors in carotid
      artery-jugular vein (CA-JV) shunt pulmonary artery hypertension model of rats.
      METHODS: Thirty-six Sprague-Dawley rats were randomized into three groups: CA-JV
      group, monocrotaline (MCT) administration group, and control group. Left CA-JV
      shunts were established in CA-JV group. Dorsal subcutaneous injections of MCT (60
      mg kg(-1)) were received in MCT group. Ligations of left common carotid artery
      and external jugular vein were performed in control group. Right ventricular
      systolic pressure (RVSP) measurement, histological evaluation of the pulmonary
      tissue, and mRNA levels of transforming growth factor beta 1 (TGFbeta1), receptor
      1 and receptor 2, were investigated after 6 weeks on MCT group, and after 12
      weeks on both control and CA-JV groups. RESULTS: Compared with control group,
      RVSP, percentage of fibrous tissue (F%) in pulmonary arterioles, mRNA levels of
      TGFbeta1, and receptors of CA-JVand MCT groups increased significantly. Severe
      hemodynamics change was found in MCT groups. On the other hand, CA-JV group
      demonstrated more obvious fibrogenesis and TGFbeta1 signals' upregulation in two
      pulmonary artery hypertension (PAH) models. CONCLUSIONS: CA-JV shunt model of
      rats was a well-established PAH animal model simulating congenital heart disease
      with systemic-pulmonary shunt.

PMID- 21893419
TI  - Infantile epilepsy associated with mosaic 2q24 duplication including SCN2A and
      SCN3A.
AB  - Epilepsies can be caused by specific genetic anomalies or by non-genetic factors,
      but in many cases the underlying cause is unknown. Mutations in the SCN1A and
      SCN2A genes are reported in childhood epilepsies; in particular SCN1A was found
      mutated in patients with Dravet syndrome and with generalized epilepsy with
      febrile seizures plus (GEFS+). In this paper we report a patient presenting with
      an atypical epileptic syndrome whose phenotype partially overlaps both Dravet
      syndrome and benign familial neonatal-infantile seizures (BFNIS). Array-CGH
      analysis suggested the presence of a mosaic duplication (about 12Mb) at the level
      of chromosome 2q23.3q24.3 involving SCN2A and SCN3A genes. Additional analyses
      (radiolabeled RFLP and quantitative PCR) confirmed the mosaicism of the
      duplication. We suggest that the array-CGH analysis is mandatory for children
      presenting with epilepsy and psycho-motor retardation even without dysmorphisms
      or other clinical features suggesting a specific genetic/epileptic syndrome. The
      analysis must nevertheless be performed taking into account the possibility of a
      mosaicism.

PMID- 21893418
TI  - Induction of regulatory Tr1 cells and inhibition of T(H)17 cells by IL-27.
AB  - Accumulating evidence indicates that IL-27, a member of the IL-12 family of
      cytokines, alleviates the severity of autoimmune diseases in both mice and men.
      The IL-27-induced activation of signal transducer and activator of transcription
      (Stat)1 and Stat3 promotes the generation of IL-10- producing type 1 regulatory T
      (Tr1) cells that inhibit effector T cells. In addition, IL-27 also suppresses the
      development of pathogenic IL-17-producing CD4(+) T cells (T(H)17) cells
      suggesting that pharmacological manipulations of IL-27 signaling pathway could be
      exploited therapeutically in regulating tissue inflammation. Here, we review how
      IL-27 controls inflammation through the regulation of Tr1 and T(H)17 responses.

PMID- 21893420
TI  - Infrainguinal bypass for peripheral arterial occlusive disease: when arms save
      legs.
AB  - OBJECTIVES: Determine if arm veins are good conduits for infrainguinal
      revascularisation and should be used when good quality saphenous vein is not
      available. DESIGN: Retrospective study. MATERIALS AND METHODS: We evaluated a
      consecutive series of infrainguinal bypass (IB) using arm vein conduits from
      March 2001 to December 2006.We selected arm vein by preoperative ultrasound
      mapping to identify suitable veins. We measured vein diameter and assessed vein
      wall quality. We followed patients with systematic duplex imaging at 1 week, 1,
      3, 6 and 12 months, and annually thereafter. We treated significative stenoses
      found during the follow-up. RESULTS: We performed 56 infrainguinal
      revascularisation using arm vein conduits in 56 patients. Primary patency rates
      at 1, 2 and 3 years were 65%, 51% and 47%. Primary assisted patencies at 1, 2 and
      3 years were 96%, 96% and 82%. Secondary patency rates at 1, 2 and 3 years were
      92%, 88% and 88%. The three-year limb salvage rate was 88%. CONCLUSIONS: We
      conclude that infrainguinal bypass using arm vein for conduits gives good patency
      rates, if selected by a preoperative US mapping to use the best autogenous
      conduit available.

PMID- 21893422
TI  - [Practice communities 2.0 in the health professional environment].

PMID- 21893421
TI  - Characterizing protein motions from structure.
AB  - To clarify the extent structure plays in determining protein dynamics, a
      comparative study is made using three models that characterize native state
      dynamics of single domain proteins starting from known structures taken from four
      distinct SCOP classifications. A geometrical simulation using the framework
      rigidity optimized dynamics algorithm (FRODA) based on rigid cluster
      decomposition is compared to the commonly employed elastic network model
      (specifically the Anisotropic Network Model ANM) and molecular dynamics (MD)
      simulation. The essential dynamics are quantified by a mode subspace constructed
      from ANM and a principal component analysis (PCA) on FRODA and MD trajectories.
      Aggregate conformational ensembles are constructed to provide a basis for
      quantitative comparisons between FRODA runs using different parameter settings to
      critically assess how the predictions of essential dynamics depend on a priori
      arbitrary user-defined distance constraint rules. We established a range of
      physicality for these parameters. Surprisingly, FRODA maintains greater intra
      consistent results than obtained from MD trajectories, comparable to ANM.
      Additionally, a mode subspace is constructed from PCA on an exemplar set of
      myoglobin structures from the Protein Data Bank. Significant overlap across the
      three model subspaces and the experimentally derived subspace is found. While
      FRODA provides the most robust sampling and characterization of the native basin,
      all three models give similar dynamical information of a native state, further
      demonstrating that structure is the key determinant of dynamics.

PMID- 21893423
TI  - A multicenter retrospective study of childhood brucellosis in Chicago, Illinois
      from 1986 to 2008.
AB  - OBJECTIVES: To determine risk factors in children for the acquisition of
      Brucella, clinical presentation, treatment, and disease outcomes. METHODS: A
      retrospective multicenter chart review was undertaken of children identified with
      brucellosis from 1986 to 2008 at three tertiary care centers in Chicago,
      Illinois, USA. The charts were reviewed for data regarding risk factors for
      acquisition, clinical presentation, and outcomes. RESULTS: Twenty-one charts were
      available for review. The median age was 6.5 years (range 2-14 years); 62% were
      female. Ethnic background was 67% Hispanic and 24% Arabic. Risk factors included
      travel to an endemic area (86%), particularly Mexico, and consumption of
      unpasteurized milk products (76%). Common findings included fever (95%),
      bacteremia (86%), elevated liver transaminases (80%), constitutional symptoms
      (76%), splenomegaly (60%), and hepatomegaly (55%). Relapse occurred in three of
      six subjects started on single drug treatment, but in only one of 15 subjects who
      started on two or more drugs (p=0.053). No relapses occurred in children whose
      initial therapy included rifampin or those administered three-drug regimens.
      CONCLUSIONS: Brucella is an infrequent pathogen but should be considered in
      children with compatible epidemiologic and clinical characteristics. Blood
      cultures should be obtained, and initial therapy with two or more drugs may
      decrease the risk of relapse.

PMID- 21893424
TI  - Can vertebral density changes be explained by intervertebral disc degeneration?
AB  - One of the major problems facing the elderly spine is the occurrence of vertebral
      fractures due to low bone mass. Although typically attributed to osteoporosis,
      disc degeneration has also been suggested to play a role in vertebral fractures.
      Existing bone adaptation theories and simulations may explain the biomechanical
      pathway from a degenerated disc to an increased fracture risk. A finite element
      model of a lumbar segment was created and calibrated. Subsequently the disc
      properties were varied to represent either a healthy or degenerated disc and the
      resulting bone adaptation was simulated. Disc degeneration resulted in a shift of
      load from the nucleus to the annulus. The resulting bone adaptation led to a
      dramatically reduced density of the trabecular core and to an increased density
      in the vertebral walls. Degeneration of just the nucleus, and in particular the
      dehydration of the nucleus, resulted in most of this bone density change.
      Additional annulus degeneration had much less of an effect on the density values.
      The density decrease in the trabecular core as seen in this study matches
      clinical observations. Therefore, bone remodeling theories can assists in
      explaining the potential synergistic effects of disc degeneration and
      osteoporotis in the occurrence of vertebral fractures.

PMID- 21893425
TI  - Beat-to-beat heart rate detection in multi-lead abdominal fetal ECG recordings.
AB  - Reliable monitoring of fetal condition often requires more information than is
      provided by cardiotocography, the standard technique for fetal monitoring.
      Abdominal recording of the fetal electrocardiogram may offer valuable additional
      information, but unfortunately is troubled by poor signal-to-noise ratios during
      certain parts of pregnancy. To increase the usability of abdominal fetal ECG
      recordings, an algorithm was developed that enhances fetal QRS complexes in these
      recordings and thereby provides a promising method for detecting the beat-to-beat
      fetal heart rate in recordings with poor signal-to-noise ratios. The method was
      evaluated on generated recordings with controlled signal-to-noise ratios and on
      actual recordings that were performed in clinical practice and were annotated by
      two independent experts. The evaluation on the generated signals demonstrated
      excellent results (sensitivity of 0.98 for SNR>=1.5). Only for SNR<2, the
      inaccuracy of the fetal heart rate detection exceeded 2 ms, which may still
      suffice for cardiotocography but is unacceptable for analysis of the beat-to-beat
      fetal heart rate variability. The sensitivity and positive predictive value of
      the method in actual recordings were reduced to approximately 90% for SNR<=2.4,
      but were excellent for higher signal-to-noise ratios.

PMID- 21893426
TI  - A theoretical model for comparing UK costs of contact lens replacement
      modalities.
AB  - PURPOSE: To develop a theoretical 'cost-per-wear' model of contact lens wear, as
      tool for UK practitioners to assist patients in determining the most cost
      effective lens replacement and wearing frequency protocols. METHODS: The annual
      cost of professional fees, contact lenses and solutions when wearing daily, two
      weekly and monthly replacement contact lenses was determined for spherical, toric
      and multifocal prescription types. This annual cost was divided by the number
      times lenses are worn per year, resulting in a cost-per-wear. RESULTS: The cost
      per-wear for two weekly and monthly replacement contact lenses is similar, both
      decreasing with increasing frequency of wear. The cost-per-wear of daily
      replacement lenses is lower than for reusable lenses when worn 1-2 days per week
      (DPW), but higher when worn 4-7 DPW. The 'cross-over point' for spherical lenses
      at which the cost-per-wear is virtually the same for the three replacement
      frequencies, approximately L2.06, occurs at 3 DPW. The cross-over point for toric
      lenses is at 4 DPW with daily compared to two weekly replacement lenses (L2.06)
      and between 2-3 DPW with daily compared to monthly replacement contact lenses
      (L2.39). The crossover point for multifocal lenses of all replacement frequencies
      is between 4 and 5 DPW (L1.79). CONCLUSIONS: In general, daily replacement
      contact lenses are more cost-effective when worn on a part-time basis (1-3 DPW)
      and reusable lenses are more cost-effective when worn full-time (4-7 DPW). This
      cost-per-wear model will assist practitioners in making an informed decision when
      offering advice to patients relating to the most suitable replacement modality.

PMID- 21893427
TI  - L-arginine trifluoroacetate salt bridges in its solid state compound: the low
      temperature three dimensional structural determination of L-arginine
      bis(trifluoroacetate) crystal and its vibrational spectral analysis.
AB  - Structural varieties of L-arginine trifluoroacetate (abbreviated as LATF) and L
      arginine bis(trifluoroacetate), LABTF, in the solid state compounds were observed
      and analyzed by the nuclear magnetic resonance (NMR) spectroscopy. The
      guanidinium-carboxylate interaction plays an important role involving in the
      crystal structure construction. Conformational changes of L-Arg(+) and L-Arg(2+)
      cations result from the intrinsic structural difference by hydrogen bonding and
      electrostatic interactions. The low-temperature structure of its crystalline
      salt, L-arginine bis(trifluoroacetate), was determined to describe the hydrogen
      bonding interactions. In comparison with the crystal structure at room
      temperature, the low-temperature L-Arg(2+) cations present tiny conformational
      difference and the rotational disorder of CF(3) group disappears. FT-IR and Raman
      spectra were investigated and hydrogen bonding interactions were analyzed on the
      basis of its vibrational spectra. Results indicate that this type interaction is
      greatly contributive to the structural features and vibrational spectral
      properties.

PMID- 21893428
TI  - Medical importance of Sindbis virus in south-west Germany.

PMID- 21893429
TI  - Second external quality assessment of the molecular diagnostic of West Nile
      virus: are there improvements towards the detection of WNV?
AB  - BACKGROUND: WNV epidemics occur worldwide, new WNV isolates were isolated in
      southern-east Europe belonging to WNV lineage 2. A first international
      proficiency study on WNV indicted that some laboratories were not able to detect
      WNV lineage 2 virus genome by their PCR diagnostic assays. Therefore an actual
      External Quality Assessment with both virus lineages was performed to monitor the
      improvements in molecular diagnostics. OBJECTIVES: To asses the proficiency of
      laboratories to detect West Nile virus with molecular diagnostic tests. STUDY
      DESIGN: A test panel of different WNV isolates and virus dilutions was given to
      26 laboratories to test the samples with their routine diagnostic methods.
      RESULTS: Twenty-one participating laboratories provided 28 data set results. WNV
      lineage 1 was detected with high overall efficiency of 92% (67.9-100%) but two
      different WNV lineage 2 strains were detected at lower rates (mean = 73%, 67.9
      75%) by the different PCR assays. 93% of the laboratories were able to detect a
      WNV lineage 1 with a concentration of 1.2*10(4)copies/ml but the detection rate
      was decreased to 68% for 1.2*10(3)copies/ml. One laboratory generated false
      positive result from the non-virus control samples and 29% of the datasets showed
      false-positive results for non-WNV flavivirus samples. CONCLUSIONS: The WNV EQA
      showed an improved proficiency of laboratories as compared to the first EQA.
      However, the data suggest that problems in the detection of both lineages were
      still present since the first proficiency test was performed in 2006. Further
      proceedings versus the detection of both lineages are needed particularly for in
      house assays.

PMID- 21893430
TI  - From genes to therapeutic targets for psychiatric disorders - what to expect?
AB  - Neuropsychiatric disorders as schizophrenia, autism and mood disorders represent
      one of the leading causes of disability. The cost of bringing a drug to the
      market is increasing and becoming more risky. Pharmaceutical investments in
      neuroscience are decreasing. At the same time we are facing an unprecedented rate
      of discovery in human genetics. Genes predisposing for common diseases including
      psychiatric disorders are being identified. The knowledge derived from the
      identification of genes relevant for psychiatric disorders holds the promise of
      providing truly innovative therapeutic interventions. The process of approving
      new psychiatric drugs, is however complex, lengthy and requires a well
      orchestrated and funded effort of multiple disciplines. In this article a brief
      overview of the key learning obtained from the conduction genome-wide association
      studies, thus far, is given in an attempt to provide a realistic view on the
      potential contribution of human genetics to drug discovery in psychiatry.

PMID- 21893431
TI  - High resolution 3D perspective of Plasmodium biology: advancing into a new era.
AB  - Apicomplexan parasites exhibit a great variety of complex life cycles that
      require adaptation to different niches of parasitism. They invade different host
      cells and highjack their biological functions. Plasmodium falciparum, responsible
      for the deadliest form of human malaria, causes disease while completely
      remodeling the erythrocytes of its human host through mechanisms that are only
      partly understood. Recent developments in ultrastructural technologies offer new
      opportunities to investigate fundamental aspects in the biology of the parasite
      in a three-dimensional (3D) perspective. Here we bring together recent work on
      host cell invasion, hemoglobin uptake, protein export and nuclear dynamics. A
      comprehensive 3D view of the ultrastructural biology of the parasite may shed new
      light on cellular mechanisms that underlie the pathogenicity of P. falciparum.

PMID- 21893433
TI  - Mre11-Rad50 complex crystals suggest molecular calisthenics.
AB  - Recently published crystal structures of different Mre11 and Rad50 complexes show
      the arrangement of these proteins and imply dramatic ligand-induced
      rearrangements with important functional consequences.

PMID- 21893434
TI  - Acinar cell carcinoma: a possible diagnosis in patients without intrapancreatic
      tumour.
AB  - BACKGROUND: Acinar cell carcinomas of the pancreas are rare neoplasms. Usually
      diagnosed at an advanced stage, in general they are large solid pancreatic
      tumours with an average size of more than 10 cm. AIMS AND RESULTS: We report 3
      cases of acinar cell carcinomas involving the peripancreatic lymph nodes, the
      liver hilum and the colon respectively, without clinical or pathological evidence
      of pancreatic tumours. These highly cellular neoplasms showed a predominantly
      acinar cell differentiation intermingled with a ductal component, with
      intracellular or extracellular mucin production by at least 25% of tumour cells.
      In addition, one case showed endocrine differentiation. Diffuse immunoreactivity
      for acinar enzymes trypsin and chymotrypsin was present in all cases. CONCLUSION:
      The occurrence of acinar cell carcinomas outside the pancreas underlines the
      notion that acinar cell carcinomas may originate in extrapancreatic sites and
      probably develop from heterotopic or metaplastic pancreatic foci present along
      the biliary tract.

PMID- 21893432
TI  - Toxoplasma gondii effectors are master regulators of the inflammatory response.
AB  - Toxoplasma is a highly successful parasite that establishes a life-long chronic
      infection. To do this, it must carefully regulate immune activation and host cell
      effector mechanisms. Here we review the latest developments in our understanding
      of how Toxoplasma counteracts the immune response of the host, and in some cases
      provokes it, through the use of specific parasite effector proteins. An emerging
      theme from these discoveries is that Toxoplasma effectors are master regulators
      of the pro-inflammatory response, which elicits many of the toxoplasmacidal
      mechanisms of the host. We speculate that combinations of these effectors present
      in certain Toxoplasma strains work to maintain an optimal parasite burden in
      different hosts to ensure parasite transmission.

PMID- 21893435
TI  - Elastography-based assessment of primary biliary cirrhosis staging.

PMID- 21893436
TI  - Chromoendoscopy in small bowel capsule endoscopy: Blue mode or Fuji Intelligent
      Colour Enhancement?
AB  - INTRODUCTION: Virtual chromoendoscopy is used to enhance surface patterns and
      colour differences. One type of virtual chromoendoscopy is the Fuji Intelligent
      Colour Enhancement (FICE). Although widely applied in conventional endoscopy,
      data on FICE application in capsule endoscopy are limited. Furthermore, the
      validity of Blue filter (feature of RAPID((r)) software) has not been examined.
      AIM/S: We aimed to qualitatively evaluate the use of FICE and Blue filter
      enhancement, in images of lesions obtained during small bowel capsule endoscopy,
      comparing them with similar, conventional (white light) images. METHODS: A total
      of 167 images (6 different lesion categories) obtained from 200 capsule endoscopy
      examinations. Two gastroenterologists examined the images with white light, FICE
      and Blue filter in regards to the visibility of blood vessels, the contrast of
      the mucosal surface, and the demarcation of lesion borders. The agreed scores
      were: improved, similar, worse. Inter-observer agreement was calculated. RESULTS:
      For all lesion categories, Blue filter provided image improvement (compared to
      white light) in 83%, (inter-observer agreement: 0.786). With FICE 1, improvement
      was observed in 34%, worse image in 55.9%, (inter-observer agreement: 0.646).
      With FICE 2, improvement was observed in 8.6%, worse in 77.5%, (inter-observer
      agreement: 0.617). With FICE 3, improvement was seen in 7.7%, worse in 79.9%
      (inter-observer agreement: 0.669). CONCLUSION: Comparing with FICE, Blue filter
      offers better image enhancement in capsule endoscopy.

PMID- 21893437
TI  - Phase II study of pharmacogenetic-tailored therapy in elderly colorectal cancer
      patients.
AB  - BACKGROUND: Retrospective analyses suggested that a pharmacogenetic approach may
      allow a tailored selection of chemotherapy for metastatic colorectal cancer. AIM:
      We conducted a phase II study of pharmacogenetic-selected first-line chemotherapy
      in elderly patients with advanced colorectal cancer, with the aim to improve
      efficacy and to reduce toxicity in this group of patients. METHODS: 24 patients
      were enrolled in this study. Chemotherapy regimen was prospectively assigned
      based on TS, DPD, ERCC-1 and UGT1A1 genotyping results. Twelve patients (50%)
      were treated with modified FOLFIRI, 11 patients (46%) with modified FOLFOX6 and 1
      (4%) with De Gramont regimen. RESULTS: A partial remission was obtained in 4
      cases (17%), stable disease in 8 cases (33%) and progressive disease in 12 cases
      (50%). Grade 3-4 neutropenia was observed in 7 patients (29%) and diarrhoea in 3
      cases (12%). The trial was then interrupted according to study design requiring
      13 partial remissions out of the first 24 patients enrolled as the necessary
      response rate level in order to continue. CONCLUSION: Prospective selection of
      chemotherapy based on TS, DPD, ERCC-1 and UGT1A1 expression in elderly advanced
      colorectal cancer patients failed to confirm previous results. A more accurate
      validation of retrospective findings is warranted before these molecular markers
      can be used for treatment selection in the clinical practice.

PMID- 21893438
TI  - Appearance concerns comparisons among persons with body dysmorphic disorder and
      nonclinical controls with and without aesthetic training.
AB  - Body dysmorphic disorder (BDD) concerns may be on a continuum with normal
      appearance concerns, differing only quantitatively. As emerging evidence suggests
      that an increased aesthetic sensitivity plays a role in BDD, individuals with BDD
      (n=50) were compared with a control group of individuals with an education or
      employment in art and design related fields (n=50) and a control group of
      individuals without aesthetic training (n=50). Participants completed a
      demographic questionnaire and a series of measures for depression, BDD
      symptomatology, and body image. Most controls (with and without aesthetic
      training) reported appearance concerns and expressed comparable ideals to those
      with BDD. However, BDD participants differed by using negative, emotive, and
      morally based descriptions for their defect(s), spending a greater time
      preoccupied with their defect(s) causing increased interference with functioning,
      performing appearance-related behaviors more frequently, and experiencing greater
      distress when performing those behaviors.

PMID- 21893439
TI  - Prevention of preterm birth.
AB  - Preterm birth (delivery before 37 completed weeks of gestation) is common and
      rates are increasing. In the past, medical efforts focused on ameliorating the
      consequences of prematurity rather than preventing its occurrence. This approach
      resulted in improved neonatal outcomes, but it remains costly in terms of both
      the suffering of infants and their families and the economic burden on society.
      Increased understanding of the pathophysiology of preterm labor has altered the
      approach to this problem, with increased focus on preventive strategies. Primary
      prevention is a limited strategy which involves public education, smoking
      cessation, improved nutritional status and avoidance of late preterm births.
      Secondary prevention focuses on recurrent preterm birth which is the most
      recognisable risk factor. Widely accepted strategies include cervical cerclage,
      progesterone and dedicated clinics. However, more research is needed to explore
      the role of antibiotics and anti-inflammatory treatments in the prevention of
      this complex problem.

PMID- 21893440
TI  - Clinical features predicting identification of CDKN2A mutations in Italian
      patients with familial cutaneous melanoma.
AB  - CDKN2A is the most common, most penetrant gene whom germline mutations
      predisposing to cutaneous familial melanoma (FAM). Multiple primary melanoma
      (MPM), early age at onset, >2 affected members and pancreatic cancer are
      consistent features predicting positive test. However, the impact that cumulative
      clinical features have on the likelihood of molecular testing is unknown. In this
      work, genotype-phenotype correlations focused on selected clinical features were
      performed in 100 Italian FAM unrelated patients. Molecular studies of CDKN2A
      mutations were performed by direct sequencing. Statistical study included
      multiple correspondence analysis, uni- and multivariate analyses, and individual
      patient's probability calculation. MPM, >2 affected family members, Breslow
      thickness >0.4mm, and age at onset <=41 years were the unique independent
      features predicting positive CDKN2A screening. The rate of positive testing
      ranged from 93.2% in the presence of all of them, to 0.4% in their absence. The
      contribution of each of them was quantified accordingly, with MPM being the most
      significant. These findings confirm previous data and add novel insights for the
      role of accurate patients' selection in CDKN2A screening.

PMID- 21893442
TI  - Prevalence of Janus Kinase 2 mutations in patients with unusual site venous
      thrombosis.
AB  - We aimed to study patients with splanchnic vein thrombosis (SVT) and cerebral
      vein thrombosis (CVT) searching for JAK2 mutations. We evaluated 14 patients
      (median age: 41.5 years) with portal vein thrombosis (PVT) = 7; mesenteric vein
      thrombosis (MVT) = 3; and CVT = 4. JAK2 V617F was assessed by allele specific PCR
      of peripheral blood DNA. In addition, DNA was sequenced for other JAK2 mutations.
      Other inherited and acquired thrombophilia risk factors were evaluated. JAK2
      V617F was positive in four out of seven patients with PVT and in one CVT patient.
      These five patients had a diagnosis of myelo-proliferative disorder (MPD) at the
      moment of the occurrence of thrombosis (n = 2) or later (n = 2). Patients with
      MVT and CVT were negative for JAK2 V617F, except one patient with CVT and a
      diagnosis of essential thrombocythemia. No other JAK2 mutations were found in
      this cohort. Besides MPD, other thrombophilia risk factors were identified in
      five patients. One patient had MPD as well as thrombophilia risk factor. In this
      group, 4 out of 7 of the patients with PVT carried the JAK2 V617F mutation with
      or without overt MPD. However, the investigation of other JAK2 mutations may not
      be necessary in patients with thrombosis at unusual sites.

PMID- 21893441
TI  - Maternal prenatal urinary phthalate metabolite concentrations and child mental,
      psychomotor, and behavioral development at 3 years of age.
AB  - BACKGROUND: Research suggests that prenatal phthalate exposures affect child
      executive function and behavior. OBJECTIVE: We evaluated associations between
      phthalate metabolite concentrations in maternal prenatal urine and mental, motor,
      and behavioral development in children at 3 years of age. METHODS: Mono-n-butyl
      phthalate (MnBP), monobenzyl phthalate (MBzP), monoisobutyl phthalate (MiBP), and
      four di-2-ethylhexyl phthalate metabolites were measured in a spot urine sample
      collected from 319 women during the third trimester. When children were 3 years
      of age, the Mental Development Index (MDI) and Psychomotor Development Index
      (PDI) were measured using the Bayley Scales of Infant Development II, and
      behavior problems were assessed by maternal report on the Child Behavior
      Checklist. RESULTS: Child PDI scores decreased with increasing loge MnBP
      [estimated adjusted beta-coefficient = -2.81; 95% confidence interval (CI): 
      4.63, -1.0] and loge MiBP (beta = -2.28; 95% CI: -3.90, -0.67); odds of motor
      delay increased significantly [per loge MnBP: estimated adjusted odds ratio (OR)
      = 1.64; 95% CI: 1.10, 2.44; per loge MiBP: adjusted OR =1.82; 95% CI: 1.24,
      2.66]. In girls, MDI scores decreased with increasing loge MnBP (beta = -2.67;
      95% CI: -4.70, -0.65); the child sex difference in odds of mental delay was
      significant (p = 0.037). The ORs for clinically withdrawn behavior were 2.23 (95%
      CI: 1.27, 3.92) and 1.57 (95% CI: 1.07, 2.31) per loge unit increase in MnBP and
      MBzP, respectively; for clinically internalizing behaviors, the OR was 1.43 (95%
      CI: 1.01, 1.90) per loge unit increase in MBzP. Significant child sex differences
      were seen in associations between MnBP and MBzP and behaviors in internalizing
      domains (p < 0.05). CONCLUSION: Certain prenatal phthalate exposures may decrease
      child mental and motor development and increase internalizing behaviors.

PMID- 21893443
TI  - [Instability in multiple atherosclerotic plaques in patients who died of acute
      myocardial infarction].
AB  - In acute coronary syndromes inflammatory process plays an important role in
      atherosclerotic plaque instability. Our aim was to evaluate the presence and
      distribution of vulnerable plaques and inflammatory infiltrates in patients who
      died of acute myocardial infarction in comparison to patients who died of non
      coronary heart disease. We analyzed pathologic studies of the heart of 68
      patients who died of acute myocardial infarction and 15 patients who died of non
      coronary heart disease. The presence of thrombus, intraplaque hemorrhage,
      endothelial rupture and inflammatory infiltrates were registered. In patients who
      died of myocardial infarction, we found thrombus in 73.5% of the involved
      arteries and in 28.7% of the non involved (p < 0.0001). Intraplaque hemorrhage
      was found in 70.5% of involved arteries and in 39.7% of the non involved (p <
      0.0001); endothelial rupture in 29.4% of involved arteries and in 3.7% of non
      involved arteries (p < 0.0001). There was no difference in the presence of
      inflammatory infiltrates (76.5% versus 68.4%). Comparing with patients who have
      died of non-coronary heart disease, the presence of thrombus was significantly
      higher (73.5% vs. 13.3%; p < 0.0001), as well as the presence of intraplaque
      hemorrhage (70.5% vs. 0%; p < 0.0001) and of inflammatory infiltrates in
      atherosclerotic plaques (76.5% vs. 46.6%; p = 0.021). In patients who died of
      acute myocardial infarction we observed plaque instability and inflammatory
      activity, not only in the infarct related artery but also in the non involved
      arteries.

PMID- 21893444
TI  - [Comparison between CKD-EPI and MDRD-equations to estimate glomerular filtration
      rate in chronic kidney disease patients].
AB  - The MDRD equation to estimate glomerular filtration rate (GFR) is the most widely
      used strategy to assess chronic kidney disease. Nonetheless, for the individual
      patient the true GFR can be underestimated with the risk of diagnosing a more
      elevated CKD stage. This novel CKD-EPI equation would improve accuracy and
      precision of estimations, and several authors recommend this new equation replace
      the former. In our country there is only a limited registration of these
      comparisons performed on a large number of patients. Therefore, our aim was to
      develop a comparison in a wide cohort of patients. The concordance between both
      equations to assign the GFR stages was determined by using the MDRD formula as a
      reference. The mean difference of GFR obtained with both equations as well as the
      Bland-Altman analysis were calculated. A cohort of 9319 individuals, of whom 67%
      were females, aged 58 +/- 20 years, with serum creatinine values of 1.6 +/- 1.03
      mg/dl, was studied. In the whole group, CKD-EPI displayed an average GFR 0.61
      ml/min/1.73 m2 larger than MDRD (p: NS). For CKD stages 2 and 3A the mean
      estimated GFR difference was 6.95 +/- 4.76 and 3.21 +/- 3.31, while the
      concordance was 81 and 74% respectively. The percentage of patients with GFR < 60
      ml/min/1.73 m2, decreased from 76.3% with the former equation to 70.1% with the
      latter. The novel equation CKD-EPI reduces the number of patients with GFR values
      lower than 60 ml/min/1.73 m2 and consequently assigns a higher GFR stage to a
      considerable quantity of individuals.

PMID- 21893445
TI  - [Quinolone resistant Campylobacter jejuni strains isolated from humans and from
      poultry].
AB  - Eight quinolone resistant Campylobacter jejuni strains isolated from humans with
      diarrheal disease were compared with 23 isolates from chicken and from laying
      hens. Samples were cultured on selective agar in microaerophilia, identified by
      conventional tests, and conserved in 17% glycerol at -70 C. Clones were
      determined by RAPD-PCR employing the 1254 primer (Stern NJ). Five patterns were
      obtained. Patterns I, II, and V were found in both poultry and human isolates.
      Pattern I was obtained from poultry in a domestic henhouse. Pattern III was only
      obtained from humans whereas pattern IV was only obtained from poultry. A 95.3%
      of clones were found in both, humans and poultry. According to these results
      colonization by quinolone resistant strains could be the origin of this human
      infection, acquired by ingestion.

PMID- 21893446
TI  - [Ultraviolet radiation impact on seasonal variations of serum 25-hydroxy-vitamin
      D in healthy young adults in Buenos Aires].
AB  - Exposure to sunlight (ES) is the main source of vitamin D. There are few reports
      regarding the seasonal variations of serum 25(OH) vitamin D in young adults and
      its correlation with ultraviolet radiation dose (UVRd). Our aims were to
      determine 25OHD variations in young adults and assess the correlation between
      25OHD levels, dietary calcium intake (DCI) and the UVRd. Eighty two healthy
      volunteers were prospectively studied: 42 women and 40 men. Serum 25OHD, calcium,
      phosphorus and magnesium were measured at the end of winter and at the end of
      summer. ES and UVRd were determined hourly in winter and summer. Seasonal
      variation in serum 25OHD levels was observed with significantly higher levels in
      summer in both gender. Serum 25OHD <20 ng/ml was more frequently found in winter
      (42.6% in women and 50% in men). The ES and UVRd were significantly lower in
      winter vs. summer. ES and UVRd positively correlated with 25OHD only in winter in
      both men and women. DCI was lower than recommended and did not correlate with
      25OHD levels.

PMID- 21893447
TI  - Neutrophil predominance in induced sputum from asthmatic patients. Therapeutic
      implications and role of clara cell 16-KD protein.
AB  - Eosinophil is considered to be a main protagonist in asthma; however, often
      discordances between clinical manifestations and response to treatment are
      observed. We aimed to determine the occurrence of neutrophil predominance in
      asthma and to identify its characteristics on the basis of clinical-functional
      features, induced sputum cellular pattern and soluble molecules, to guide the
      appropriated anti-inflammatory therapy. A total of 41 patients were included in
      randomized groups: 21-40 year-old, with stable mild-to-severe asthma, steroid
      naive and non-smokers. An induced sputum sample was obtained under basal
      conditions, a second one after treatment with budesonide (400 ug b.i.d.) or
      montelukast (10 mg/d) for six weeks, and a final one after a 4-week washout
      period. By cytospin we evaluated eosinophil (EP) or neutrophil predominance (NP),
      and in supernatant we determined LTE4, and CC16. Peak expiratory flow variability
      (PEFV) was measured. A total of 23/41 patients corresponded to EP and 18/41
      patients to NP. The PEFV was higher in EP than in NP. LTE4 was higher with NP
      than with EP. No difference was found for CC16. Montelukast reduced the
      predominant cell in both subsets, whereas budesonide only reduced eosinophils in
      EP. Budesonide and montelukast reduced PEFV in EP but not in NP. Considering the
      total treated-samples in each subset, CC16 level increased significantly in EP.
      IN CONCLUSION: a NP subset of asthmatic patients was identified. These patients
      show a lower bronchial lability; the leukotriene pathway is involved which
      responds to anti-leukotriene treatment. This phenotype shows a poor recovery of
      CC16 level after treatment.

PMID- 21893448
TI  - [Antibody deficiencies. A survey from three Clinical Immunology Centers for
      adults in Buenos Aires city].
AB  - Antibody deficiency (AD) comprises a group of diseases characterized by the
      inability to develop an effective antibody mediated immune response. These
      patients suffer mainly of encapsulated extracellular bacterial infections of the
      respiratory tract. The aim of our study was to describe the clinical
      characteristics of 128 patients with suspected or confirmed AD who were referred
      to 3 immunodeficiency centers for adults, from June 2004 to December 2009. Three
      of these patients (2.3%) consulted for recurrent infections only once, without
      sufficient data for a proper classification, and were excluded. Of the remaining
      125 patients, in 21 (16.8%) AD was excluded, 8 cases (6.4%) were diagnosed with
      secondary antibody immunodeficiency (SAD) and 96 (76.8%) with primary antibody
      immunodeficiency (PAD). SAD causes were: one renal failure, one phenytoin use,
      two monoclonal gammopathy and four B cell lymphoma. The causes of these 96 PAD
      were: 57 common variable immunodeficiency, 12 X-linked agammaglobulinaemia, 10
      selective IgA deficiency, seven IgG1 deficiency, three hyper-IgM syndrome, three
      IgM deficiency, two X-linked proliferative syndrome, one Good syndrome and one
      antibody functional deficiency. Sixty-seven patients were in follow up at the
      time of completion of the study, 25 of them were on follow up at the beginning of
      the study. Among the 58 patients with indication of gamma globulin replacement
      therapy, 54 were in treatment at the end of the study. In four patients the
      initial diagnosis of PAD was not confirmed.

PMID- 21893449
TI  - Premalignant quiescent melanocytic nevi do not express the MHC class I chain
      related protein A.
AB  - The MHC class I chain-related protein A (MICA) is an inducible molecule almost
      not expressed by normal cells but strongly up-regulated in tumor cells. MICA
      expressing cells are recognized by natural killer (NK) cells, CD8+ abTCR and
      gdTCR T lymphocytes through the NKG2D receptor. Engagement of NKG2D by MICA
      triggers IFN-g secretion and cytotoxicity against malignant cells. Although most
      solid tumors express MICA and this molecule is a target during immune
      surveillance against tumors, it has been observed that high grade tumors from
      different histotypes express low amounts of cell surface MICA due to a
      metalloprotease-induced shedding. Also, melanomas develop after a complex process
      of neotransformation of normal melanocytes. However, the expression of MICA in
      premalignant stages (primary human quiescent melanocytic nevi) remains unknown.
      Here, we assessed expression of MICA by flow cytometry using cell suspensions
      from 15 primary nevi isolated from 11 patients. When collected material was
      abundant, cell lysates were prepared and MICA expression was also analyzed by
      Western blot. We observed that MICA was undetectable in the 15 primary nevi
      (intradermic, junction, mixed, lentigo and congenital samples) as well as in
      normal skin, benign lesions (seborrheic keratosis), premalignant lesions (actinic
      keratosis) and benign basocellular cancer. Conversely, a primary recently
      diagnosed melanoma showed intense cell surface MICA. We conclude that the onset
      of MICA expression is a tightly regulated process that occurs after melanocytes
      trespass the stage of malignant transformation. Thus, analysis of MICA expression
      in tissue sections of skin samples may constitute a useful marker to
      differentiate between benign and malignant nevi.

PMID- 21893450
TI  - [Increase of regulatory T cells in the lymph node of cathepsin L mutant mice].
AB  - Regulatory CD4+CD25+Foxp3+ T cells (Treg) have been implicated in different
      pathologies including cancer, infections and autoimmune diseases and in the
      rejection of allogeneic organ transplantation. Thus, modulation of Treg activity
      has a great potential in the treatment of these pathologies. Herein, we evaluated
      the influence of cathepsin L (CTSL) on Treg homeostasis. CTSL mutant mice
      (CTSLnkt/nkt) showed a decrease in the absolute number of thymic Treg cells. In
      contrast, the absolute number of lymph node Treg cells and their frequency within
      CD4+ cells were increased. The absence of CTSL activity in CD4+ T cells -and not
      in their environment- increased the proliferation rate of lymph node CD4+ T
      cells. Treg and T CD4+ conventional (CD4+CD25-Foxp3-) cells from mutant mice
      showed similar increases in their proliferative levels as compared with control
      mice, suggesting that although proliferation contributes to the increases in
      their number, the augmentation in the frequency of Treg cells is not only
      associated to increases in proliferation. Furthermore, the Treg apoptosis rate
      was not decreased in the lymph node of CTSLnkt/nkt mice. Taking into account that
      the daily CD4+ thymic production is diminished in mutant mice, our results
      suggest that peripheral Treg increases are probably not the result of increased
      thymic output and raise the possibility that a conversion to Treg phenotype would
      be favored in the CD4+ T cells peripheral pool of CTSL mutant mice.

PMID- 21893451
TI  - [Temporary occlusion of atrial septal defect in the Lutembacher syndrome].
AB  - We report the case of an 82 year-old woman with symptoms of advanced heart
      failure and pulmonary arterial hypertension. An echocardiogram showed an ostium
      secundum type atrial septal defect and concomitant mitral valve stenosis
      (Lutembacher syndrome). Echocardiographic assessment of mitral pathology was
      hampered by the interatrial septal defect. Transient percutaneous occlusion test
      of the atrial septal defect was performed and severe mitral valve stenosis was
      detected. Atrial septal defect size modified the clinical manifestations and the
      transient occlusion test helped to decide the therapeutic strategy.

PMID- 21893452
TI  - [Granulomatous meningitis, crescentic glomerulonephritis and vasculitis].
AB  - Meningeal involvement is an infrequent manifestation of Wegener's granulomatosis.
      Clinical manifestations can be headache with high protein level in the
      cerebrospinal fluid and an enhanced MRI signal of granulomatous thickening of the
      duramater in the brain. We report a 57 year-old male with Wegener granulomatosis
      with onset manifestations of asymptomatic granulomatous meningitis, upper
      respiratory tract, ears and orbits involvement. He progressively developed ANCA
      positive multiple mononeuritis and crescentic glomerulonephritis. The diagnostic
      confirmation of Wegener's granulomatosis based on a positive ANCA test and on the
      evidence of systemic disease (crescentic glomerulonephritis and involvement of
      the upper respiratory tract, ears, orbits, peripheral nerves and duramater)
      allowed a prompt initiation of aggressive immunosuppressive treatment with
      systemic cyclophosphamide and high - dosis corticosteroids. The patient entered
      into a sustained clinical remission with mild residual neurosensorial hearing
      loss and renal failure.

PMID- 21893453
TI  - [Post-traumatic false (pseudo) aneurysm of the left main coronary artery].
AB  - Coronary pseudo-aneurysm is an extremely rare entity. Its natural history is
      scarcely known and its treatment is controversial. We report a case of pseudo
      aneurysm of the left main coronary artery associated with an antero-apical
      infarct of the left ventricle diagnosed five years after a cardiac arrest
      following a non-penetrating thoracic trauma. The patient was treated
      conservatively because percutaneous or surgical correction were not considered
      suitable for this lesion. A multidetector computed tomography coronary angiogram
      performed 10 years after the initial event showed no evidence of progression.

PMID- 21893454
TI  - [Rhinosinusal mucormycosis].

PMID- 21893455
TI  - [Three-dimensional reconstruction of persistent left superior vena cava during
      atrial fibrillation ablation].

PMID- 21893456
TI  - [Dilated left atrial appendage by peri-prosthetic mitral leak].

PMID- 21893457
TI  - [Postpartum cerebral venous sinus thrombosis].

PMID- 21893458
TI  - [Update on the treatment of endemic hemolytic uremic syndrome. Pathogenesis and
      treatment of the most severe systemic complication of infections by Shiga toxin
      producing Escherichia coli].
AB  - The typical form of hemolytic uremic syndrome (HUS) is the major complication of
      Shiga toxin-producing Escherichia coli (STEC) infections. HUS is a critical
      health problem in Argentina since it is the main cause of acute renal failure in
      children and the second cause of chronic renal failure, giving account for 20% of
      renal transplants in children and adolescents in our country. In spite of the
      extensive research in the field, the mainstay of treatment for patients with HUS
      is supportive therapy, and there are no specific therapies preventing or
      ameliorating the disease course. In this review, we present the current knowledge
      about pathogenic mechanisms and discuss traditional and innovative therapeutic
      approaches, with special focus in national status and contributions made by
      Argentinean groups.

PMID- 21893459
TI  - [Epigenetics and epigenome. A step forward in the etiology and potential
      treatment of neurological diseases].
AB  - The mechanisms of epigenetic regulation play an important role in the development
      and function of body systems. Failure in the maintenance of this regulation as
      well as environmental factors could contribute to the development of multiple
      diseases in genetically predisposed patients. Although the molecular mechanisms
      responsible for the etiology of most diseases are unknown, there is evidence of
      both genetic and environmental factors that could influence this development.
      Recent findings involve epigenetic mechanisms in the origin of various diseases.
      This review aims to describe in detail the mechanisms of epigenetic regulation
      and the known findings involving the dysfunction of these mechanisms as a
      possible cause of various diseases.

PMID- 21893460
TI  - [Lymphangioleiomyomatosis: an orphan disease in search for treatment].

PMID- 21893461
TI  - [Juan Carlos Fasciolo, disciple of Houssay and discoverer of angiotensin].

PMID- 21893462
TI  - [Clinicopathological conferences].

PMID- 21893463
TI  - The huge world of small RNAs: regulating networks of microRNAs (review).
AB  - MicroRNAs (miRNAs) are a recently discovered class of small, non-coding RNAs
      which do not code proteins. MiRNAs regulate gene expression by inhibiting protein
      translation from the messenger RNA. MiRNAs may function in networks, forming a
      complex relationship with diseases. Furthermore, specific miRNAs have significant
      correlation with diseases of divergent origin. After identification of disease
      associated miRNAs, their tissue expression could be altered in a beneficial way
      by inhibiting or mimicking their effects. Thus, modifying the expression of
      miRNAs is a potential future gene-therapeutic tool to influence post
      transcriptional regulation of multiple genes in a single therapy. In this review
      we introduce the biogenesis, mechanism of action and future aspects of miRNAs.
      Research on the post-transcriptional regulation of gene expression by miRNA may
      reshape our understanding of diseases and consequently may bring new diagnostic
      markers and therapeutic agents. Therapeutic use of miRNAs is already under
      clinical investigation in RNA interference trials.

PMID- 21893464
TI  - Non-ST elevation myocardial infarction: a new pathophysiological concept could
      solve the contradiction between accepted cause and clinical observations.
AB  - Non-ST elevation myocardial infarction (NSTEMI) and ST elevation infarction have
      many differences in their appearance and prognosis. A comprehensive search made
      us form a new hypothesis that a further cause also existsin NSTEMI: an acute,
      critical increase in the already existing high microvascular resistance in
      addition to the subtotal coronary artery occlusion. Various findings and studies
      can be interpreted only by our hypothesis: hemodynamic findings, ECG changes,
      autopsy reports and clinical observations (different long-time prognosis and
      different result of acute revascularization therapy in NSTEMI, similarities of
      NSTEMI with other clinical symptoms where increased microvascular resistance can
      be supposed without coronary artery disease). OBJECTIVE: Despite similarities in
      the underlying pathologic mechanism non-ST elevation myocardial
      infarction(NSTEMI) and ST elevation infarction (STEMI) have many differences in
      their clinical presentation and prognosis. METHOD: A systematic review of the
      literature about NSTEMI and the blood supply of the myocardium made us form a
      hypothesis that a further cause also exists in addition to the accepted cause of
      NSTEMI (subtotal coronaryartery occlusion): an acute, critical increase in an
      already existing high intramyocardial microvascular resistance. EVIDENCE:
      Knowledge about microcirculation disturbances in ischemic heart disease and
      development of microcirculation damage can be fitted in our hypothesis. Various
      findings and studies can be interpreted only by our hypothesis: hemodynamic
      findings, ECG changes, autopsy reports and clinical observations about NSTEMI.
      The latest ones involve the different long-time prognosis and different result of
      acute revascularization therapy in STEMI and NSTEMI. Regarding the repolarization
      changes on the ECG NSTEMI shows similarities with other clinical symptoms where
      increased intramyocardial microvascular resistance can be supposed without
      coronary artery disease: false positive exercise stress test, supraventricular
      tachycardia, left ventricular strain and conduction disturbances. CONCLUSION: The
      acute treatment of NSTEMI should aim to improve the blood inflow to the stiff
      myocardiumand/or impaired microvascular system and decrease the high
      microvascular resistance.

PMID- 21893465
TI  - Comparison and recalculation of the very different QTc interval durations in
      young healthy women.
AB  - The aim was to use some simple way for easier comparison, other expression or
      recalculation of the QTc duration from one formula to another in order to remove
      the large QTc differences. METHODS AND RESULTS: The QT interval duration in 138
      young healthy women was taken from our archive. The measured QT interval was
      corrected for heart rate (QTc) according to nine published regression equations
      (Bazett, Fridericia, Hodges, Sarma, Lecocq, Rautaharju, Sagie=Framingham,
      Arrowood, Malik) and compared mathematically by the Pearson correlation
      coefficient R and graphically by linear correlation.Correlation between two
      different QTc durations can be of three kinds: small (e.g. Bazett's versus
      Malik's formulas, R=0.0525, p=0.5405, the QTc values are much dispersed in the
      graph), larger (Malik's versus Sarma's formulas, R=0.939, p<0.01, the values are
      less dispersed), and identical (the Rautaharju's versus Arrowood's formulas,
      R=1.000, p<0.01, all QTc points are situated on one line). The linear correlation
      QTc1 = a+b.QTc2 enables recalculation from one QTc formula into another, if
      necessary.In conclusion, the QTc interval durations are differently long
      according to the QTc formula used. The correlations with the large Pearson R
      coefficient indicate the QTc pairs inappropriate for recalculation, the small R
      values indicate the appropriate pairs for recalculation.

PMID- 21893467
TI  - Relationship between the heart rate and E/A ratio in athletic and non-athletic
      males.
AB  - To clarify whether the higher E/A quotient of male athletes is a favourable
      change in the intrinsic relaxation properties of the left ventricle. METHODS:
      Peak early (E) and atrial blood flow velocities (A) were assessed by Doppler
      echocardiography at rest in 1237 males (939 athletes) in Hungary. Data were
      collected between 1993 - 2009. Relationship between E/A and resting heart rate
      (HR), was determined by linear regression analysis. RESULTS: The E/A decreased
      with age, the rate of decrease was slower in the physically trained subjects,
      except in children. In children, adolescent-young and young adult subjects E/A
      against HR equations of the athletic and nonathletic groups were similar,
      differences between the means were only due to the differences of the HR. In the
      31 - 44 yr old males, the intercepts of the athletes' regression lines were
      higher. The oldest (>44 yr) active subjects showed a significant regression while
      sedentary males did not. CONCLUSIONS: The HR-independent beneficial effect of
      regular physical training on the diastolic function manifests itself at the older
      ages. The impact of resting HR should always be taken into consideration when
      assessing intergroup differences in the E/A ratio, especially when studying the
      effect of exercise training upon cardiac function.

PMID- 21893466
TI  - The effect of dietary hempseed on atherogenesis and contractile function in
      aortae from hypercholesterolemic rabbits.
AB  - Hempseed contains a unique combination of both omega-3 and omega-6
      polyunsaturated fatty acids. In other studies, supplementation of the diet with
      selected polyunsaturated fatty acids has induced significant, beneficial
      cardiovascular effects. The purpose of the present study is to determine if
      hempseed ingestion over an 8-week period may provide protection to rabbits
      against the deleterious effects associated with dietary cholesterol
      supplementation. METHODS: Male albino New Zealand White rabbits were randomly
      divided into one of six groups: the control diet (RG), the control diet then
      supplemented with (wt/wt) 5% coconut oil (CO), or 10% hempseed (HP), or 0.5%
      cholesterol (OL), or with both 10% hempseed and 0.5% cholesterol (OLHP) or with
      10% hempseed that was partially delipidated (SC). Each day the rabbits were fed
      125 grams of the appropriate diet over an 8-week period. Fatty acid analysis of
      tissue and diets was determined using gas chromatography. Vascular function
      testing of aortic rings was done in order to assess the response of the tissue to
      both contraction and relaxation stimuli. Aortic atherosclerotic plaque was
      quantified. RESULTS: Cholesterol supplementation to the diet induced significant
      aortic plaque development. Dietary hempseed did not generate protection. The
      aorta obtained from rabbits fed the cholesterol-supplemented chow also exhibited
      defects in their contractile responses to KCl and norepinephrine and in
      relaxation to sodium nitroprusside (SNP).The addition of hempseed to this diet
      did not generate any improvement in contractile responses but had a modest
      protective effect on the cholesterol-induced defects in SNP-induced relaxation.
      CONCLUSIONS: Our data demonstrate that dietary hempseed provides mildly
      beneficial effects against contractile dysfunction associated with
      atherosclerotic vessels in the cholesterol-fed rabbit.

PMID- 21893468
TI  - Preserved structural and functional characteristics of common carotid artery in
      properly treated normoglycemic women with gestational diabetes mellitus.
AB  - Women with gestational diabetes mellitus (GDM) are at high risk of subsequently
      developing type 2 diabetes mellitus which is an important cardiovascular risk
      factor. We have evaluated whether preclinical morphological and functional
      arterial changes are present in GDM. Diameter, intima-media thickness (IMT),
      intima-media cross-section area (IMCSA) and elasticity features (compliance,
      distensibility coefficient, circumferential strain, stiffness index (SI) alpha
      and beta, incremental elastic modulus) of the common carotid arteries (CCA) were
      studied in the 3rd trimester in 25 women with GDM, and 17 normal pregnant women
      matched for age and body mass index using an ultrasonographic vessel wall
      movement tracking system and applanation tonometry. Mean IMT, IMCSA and SI alpha
      tended to be larger, whereas compliance was smaller in women with GDM but none of
      these differences were significant. Serum glucose (4.99 +/- 0.51 vs. 4.79 +/-
      0.61 mmol/L, p=0.37) and HbA1c (5.33 +/- 0.27 vs. 5.36 +/- 0.47 mmol/L, p=0.85)
      proved normoglycemia in both groups. In conclusion, by the combination of methods
      we applied in this case control study, neither morphological nor functional
      characteristics of large elastic arteries differ significantly between well
      treated normoglycemic women with GDM and non-diabetic pregnant women in the 3rd
      trimester.

PMID- 21893469
TI  - Influence of resistance training on cardiorespiratory endurance and muscle power
      and strength in young athletes.
AB  - The purpose of this study was to investigate the influence of additional
      resistance training on cardiorespiratory endurance in young (15.8 +/- 0.8 yrs)
      male basketball players. Experimental group subjects (n=23) trained twice per
      week for 12 weeks using a variety of general free-weight and machine exercises
      designed for strength acquisition, beside ongoing regular basketball training
      program. Control group subject (n=23) participated only in basketball training
      program. Oxygen uptake (VO(2max)) and related gas exchange measures were
      determined continuously during maximal exercise test using an automated
      cardiopulmonary exercise system. Muscle power of the extensors and flexors was
      measured by a specific computerized tensiometer. Results from the experimental
      group (VO(2max) 51.6 +/- 5.7 ml.min(-1).kg(-1) pre vs. 50.9 +/- 5.4 ml.min(
      1).kg(-1) post resistance training) showed no change (p>0.05) in
      cardiorespiratory endurance, while muscle strength and power of main muscle
      groups increased significantly. These data demonstrate no negative
      cardiorespiratory performance effects on adding resistance training to ongoing
      regular training program in young athletes.

PMID- 21893470
TI  - Examining physical activity and inactivity in 9-12 years old children.
AB  - Information about children's daily physical activity in Eastern-Europe is
      essential because of the increasing prevalence in overweight and obesity. Sixty
      three children (age=11.16 +/- 1.10 years; 33 boys and 30 girls) from two public
      elementary schools had their physical activity objectively measured using uni
      axial accelerometer every 5 seconds for five consecutive days (3 weekdays, 2
      weekend days). After data cleaning, 10 children were excluded from database.
      There were no significant differences in boys' and girls' BMI (17.6 +/- 2.2 vs.
      17.1 +/- 2.4) and BF% (18.0 +/- 5.2 vs. 19.4 +/- 5.0). Children engaged in more
      sedentary, light, moderate, and vigorous physical activity and had higher counts
      per minute during weekdays compared to weekend days. There were no sex
      differences in moderate to vigorous physical activity (87.6 +/- 22.4 vs. 93.5 +/-
      20.6 min and 53.6 +/- 21.3 vs. 59.4 +/- 22.0 min) during weekday and weekend
      days. Data indicated that 96% of the girls and 92% of the boys met the
      international physical activity guideline for children of 60 minutes of MVPA, on
      weekdays.

PMID- 21893471
TI  - Exercise changes volatiles in exhaled breath assessed by an electronic nose.
AB  - Exercise-caused metabolic changes can be followed by monitoring exhaled
      volatiles; however it has not been previously reported if a spectrum of exhaled
      gases is modified after physical challenge. We have hypothesized that changes in
      volatile molecules assessed by an electronic nose may be the reason for the
      alkalization of the exhaled breath condensate (EBC) fluid following physical
      exercise.Ten healthy young subjects performed a 6-minute running test. Exhaled
      breath samples pre-exercise and post-exercise (0 min, 15 min, 30 min and 60 min)
      were collected for volatile pattern ("smellprint") determination and pH
      measurements (at 5.33 kPa CO2), respectively. Exhaled breath smellprints were
      analyzed using principal component analysis and were related to EBC
      pH.Smellprints (p=0.04) and EBC pH (p=0.01) were altered during exercise
      challenge. Compared to pre-exercise values, smellprints and pH differed at 15
      min, 30 min and 60 min following exercise (p<0.05), while no difference was found
      at 0 min post-exercise. In addition, a significant correlation was found between
      volatile pattern of exhaled breath and EBC pH (p=0.01, r=-0.34).Physical exercise
      changes the pattern of exhaled volatiles together with an increase in pH of
      breath. Changes in volatiles may be responsible for increase in EBC pH.

PMID- 21893472
TI  - Complex effects of imatinib on spontaneous and oxytocin-induced contractions in
      human non-pregnant myometrium.
AB  - Human myometrium includes two important cell populations involved in its
      contractility: smooth muscle fibers and interstitial cells. The pacemaking
      mechanism is not yet identified, but it is possible that myometrial smooth muscle
      cells contract in response to a signal generated by c-kit positive interstitial
      cells. The aim of this study was to investigate the effects of imatinib as a c
      kit receptor antagonist on the spontaneous or oxytocin (OT) induced contractions
      of human non-pregnant myometrium in vitro. Myometrial strips were obtained from
      non-pregnant women (reproductive age) undergoing hysterectomy for benign
      indications. The strips were suspended in organ baths for recording of isometric
      tension. Imatinib effects were assessed on spontaneous contraction and after
      preexposure to OT.Direct exposure of myometrial strips to imatinib inhibits both
      amplitude and frequency of contractions (80-320 MUM) in a dose dependent manner.
      Amplitude reverted back to 90% of the baseline amplitude by consequent addition
      of imatinib (until 480 MUM). Total inhibition of myometrial contraction was
      obtained after addition of OT 60 nM. If myometrium was pre-exposed to OT (320
      nM), imatinib 80-160 MUm increased amplitude, while decreasing frequency. These
      data provide evidence that telocytes may be involved as modulators of the
      spontaneous contractions of the non-pregnant human uterus, via a tyrosine-kinase
      independent signaling pathway.

PMID- 21893473
TI  - Does oxidative stress play a role in altered plasma protein homeostasis in
      pregnancy-induced hypertension?
AB  - BACKGROUND: Pregnancy-induced hypertension (PIH) is associated with oxidative
      stress and low plasma proteins. This study explored the effect of oxidative
      stress on plasma protein level in PIH. METHODS: Serum total proteins (TP),
      albumin, globulin, malondialdehyde, protein carbonyls (PC) and protein bound
      sialic acid (PBSA) were measured in gestational hypertensive, pre-eclamptic,
      eclamptic and healthy pregnant women (n=20/group). Serum proteins were separated
      by electrophoresis for assessing protein damage. RESULTS: Serum TP and albumin
      decreased and malondialdehyde, PC & PBSA increased significantly in all PIH
      subgroups as compared to healthy pregnant subjects. Serum globulin levels
      decreased only in eclampsia. Malondialdehyde and PC negatively correlated with
      albumin level. Protein fragmentation and aggregation in eclampsia were evident
      from electrophoretogram. CONCLUSION: We conclude that oxidative damages to
      proteins contribute to decreased serum protein levels in PIH and hypersialylation
      of plasma proteins is probably body's protective mechanism to combat oxidative
      protein damage in PIH.

PMID- 21893474
TI  - An enhanced method for accessory pathway localization in case of Wolff-Parkinson
      White syndrome.
AB  - This paper presents an analysis of the Arruda accessory pathway localization
      method for patients suffering from Wolff-Parkinson-White syndrome, with
      modifications to increase the overall accuracy. The Arruda method was tested on a
      total of 79 cases, and 91.1% localization performance was reached. After a deeper
      analysis of each decision point of the Arruda localization method, we considered
      that the lead aVF was not as relevant as other leads (I, II, III, V1) used. The
      branch of the decision tree, which evaluates the left ventricle positions, was
      entirely replaced using different decision criteria based on the same biological
      parameters. The modified algorithm significantly improves the localization
      accuracy in the left ventricle, reaching 94.9%. An accurate localization
      performance of non-invasive methods is relevant because it can enlighten the
      necessary invasive interventions, and it also reduces the discomfort caused to
      the patient.

PMID- 21893475
TI  - Fasting increases palmitic acid incorporation into rat hind-limb intramuscular
      acylglycerols while short-term cold exposure has no effect.
AB  - The aim of the study was to investigate the palmitic acid incorporation into
      intramuscular acylglycerols in perfused hind-limb skeletal muscles of different
      fibre types in rats either fasted for 48 h or exposed to cold (6  degrees C) for
      12 h. Hind-limb preparations of fasted and cold exposed rats were perfused with
      buffers containing tritium labelled and cold palmitic acid. Palmitic acid
      incorporation into intracellular lipid pools in the soleus, plantaris, red and
      white gastrocnemius and red and white quadriceps was measured. It was found that
      fasting increased approximately 2-fold palmitic acid incorporation in all muscles
      examined regardless of the fibre type composition of the muscle. On the other
      hand, exposure to cold had no effect on the palmitic acid incorporation into
      intramuscular acylglycerols regardless the muscle fibre type. The increased
      incorporation of palmitic acid into acylglycerols in fasted animals is in line
      with data showing that 48 h fasting stimulates the expression of plasma membrane
      proteins putatively facilitating fatty acid uptake. It appears that although 12 h
      cold exposure increases the use of fatty acids as energy substrates it does not
      alter the incorporation of palmitic acid into intramuscular acylglycerols in the
      perfused rat hind-limb.

PMID- 21893477
TI  - [Dipeptidyl-peptidase-4 inhibitors (gliptins): a new class of oral antidiabetic
      drugs].
AB  - Nearly 90% of the diabetic patients are suffering of type 2 diabetes while
      approximately 60-65% of patients with type 2 diabetes are treated with oral
      antidiabetic drugs. In the last couple of years a new treatment option, namely
      incretin-based therapy, became available. The dipeptidyl-peptidase-4-inhibitors
      (gliptins) are designated as incretin enhancers. Using gliptins, sustained
      glycemic control can be achieved without gaining weight and increasing the risk
      of hypoglycemia. All gliptins (sitagliptin, vildagliptin, saxagliptin,
      linagliptin) can be used as tablets without a need for dose titration. For
      treating patients with type 2 diabetes, gliptins can primarily be used in
      combination with metformin.

PMID- 21893478
TI  - [Role of gastrointestinal inflammations in the development and treatment of
      depression].
AB  - Recent studies have revealed that inflammation, among other factors, may be
      involved in the pathogenesis of depression. One line of studies has shown that
      depression is frequently associated with manifest gastrointestinal inflammations
      and autoimmune diseases as well as with cardiovascular diseases,
      neurodegenerative diseases, type 2-diabetes and also cancer, in which chronic low
      grade inflammation is a significant contributing factor. Thus depression may be a
      neuropsychiatric manifestation of a chronic inflammatory syndrome. Another line
      of studies has shown that the primary cause of inflammation may be the
      dysfunction of the "gut-brain axis". Although, this is a bidirectional mechanism,
      life style factors may primarily affect the symbiosis between host mucous
      membrane and the microbiota. Local inflammation through the release of cytokines,
      neuropeptides and eicosanoids may also influence the function of the brain and of
      other organs. Role of metabolic burst due to inflammation represents a new aspect
      in both pathophysiology and treatment of the depression. Finally, an increasing
      number of clinical studies have shown that treating gastrointestinal
      inflammations with probiotics, vitamin B, D and omega 3 fatty acids, through
      attenuating proinflammatory stimuli to brain, may also improve depression
      symptoms and quality of life. All these findings justify an assumption that
      treating gastrointestinal inflammations may improve the efficacy of the currently
      used treatment modalities of depression and related diseases. However, further
      studies are certainly needed to confirm these findings.

PMID- 21893479
TI  - [Changes in the incidence of multiresistant pathogens and its consequences in the
      intensive care unit].
AB  - Incidence of nosocomial infections and antibiotics resistance in intensive care
      units is increasing worldwide. Blood-stream infections of Gram-negative non
      fermentive bacteria are associated with higher mortality. AIM AND METHODS: The
      aim of this study was to compare the antibiotic sensitivity of nosocomial blood
      stream infections between years 2008-2010. RESULTS: There was no difference in
      the sensitivity of methycillin-resistant Staphylococcus aureus and extended
      spectrum beta lactamase producing Klebsiella spp. and Escherichia coli infections
      between the two years examined. Antibiotic resistance of Acinetobacter baumannii
      and Pseudomonas infections showed a marked increase in 2010 when compared to that
      found in 2008: there was no multiresistant Acinetobacter infection in samples
      obtained in 2008, but all these infections were found to be sensitive only to
      colistin in samples investigated in 2010. Sensitivity of Pseudomonas infections
      to carbapenems and piperacillin/tazobactam decreased significantly during this
      time. In addition, the authors found that the mortality of multiresistant Gram
      negative blood-stream infections was higher compared to that caused by non
      multiresistant bacteria. CONCLUSIONS: These results emphasize the importance of
      infection control, adequate dosing and timing of antibiotics, and an appropriate
      number of nurses in intensive care unit.

PMID- 21893480
TI  - [Polarized light as an epigenetic factor in inhibition of inflammation; a genome
      wide expression analysis in recurrent respiratory diseases of children].
AB  - Whole-body polarized light therapy has been primarily investigated in various
      clinical observations and in a few in vitro model systems. AIMS: In the present
      study, clinical and molecular effects of whole-body polarized light treatment on
      children suffering from recurrent respiratory infection were studied. METHODS:
      Incidence and duration of respiratory symptoms as well as the length of
      appropriate antibiotic therapy have been measured. Simultaneously, genome-wide
      gene expression pattern was examined by whole genome cDNA microarray in
      peripheral lymphocytes of children. RESULTS: Twenty of twenty five children
      showed a marked clinical improvement, while in five of twenty five had poor or no
      changes. Gene expression pattern of the peripheral lymphocytes of the patients
      was compared in favorable and poor responders. Lymphocytes of the children with a
      documented improved clinical response to polarized light therapy showed a
      decrease in the expression of chemokine genes, such as CXCL1, CXCL2, IL-8 and in
      that of the tumor necrosis alpha (TNFalpha) gene. On the contrary, a rapid
      elevation was found in the expression of gene encoding for CYP4F2, a leukotriene
      B(4)-metabolizing enzyme. In children with poor clinical response to polarized
      light therapy, no similar changes were detected in the gene expression pattern of
      the lymphocytes. CONCLUSIONS: Improved clinical symptoms and modified gene
      expression profile of lymphocytes reveals anti-inflammatory effect upon whole
      body polarized light irradiation.

PMID- 21893481
TI  - [Diaphragmatic hernia or hiatus hernia: a diagnostic problem in 5-month-old
      infant].
AB  - Authors present a case of a 5-month-old infant, in whom following an uneventful
      perinatal adaptation, symptoms of recurrent respiratory infections, vomiting and
      growth failure developed. Based on chest X-ray, right-sided diaphragmatic hernia
      was suspected. However, barium swallow examination delineated the stomach above
      the right diaphragm. The case report draws attention to the differential
      diagnostic difficulties between congenital diaphragmatic and hiatal hernia.

PMID- 21893483
TI  - Management of the greater trochanteric pain syndrome: a systematic review.
AB  - INTRODUCTION: Greater trochanteric pain syndrome (GTPS) is a debilitating
      condition characterized by lateral hip pain located at or around the greater
      trochanter. SOURCE OF DATA: We performed a comprehensive search of Pubmed,
      Medline, Ovid, Google Scholar and Embase databases, from inception of the
      database to 20th of June 2011, using a variety of keywords. We identified 52
      relevant abstracts of articles published in peer-reviewed journals. Fourteen
      studies reporting the outcomes of patients undergoing conservative and surgical
      management of GTPS were selected. AREAS OF AGREEMENT: Significant pain relief and
      improved outcomes were observed after conservative and surgical management of
      GTPS. The modified Coleman methodology score averaged 44.7 (range from 14 to 82),
      evidencing an overall low-to-moderate quality of the studies. Repetitive low
      energy radial shock wave therapy and home training approach provide beneficial
      effect over months, with almost 80% success rate at 15 months. AREAS OF
      CONTROVERSY: Poor available data extracted from small studies do not allow
      definitive conclusions to be drawn on the best treatment for GTPS. GROWING
      POINTS: Further multi-centre prospective studies are necessary to confirm the
      general validity of the findings reported. AREAS TIMELY FOR DEVELOPING RESEARCH:
      Future research and trials should focus on the application and effectiveness of
      the various conservative modalities for management of GTPS. CONCLUSION: The
      effectiveness of the various treatment modalities needs to be tested in carefully
      conducted randomized controlled trials.

PMID- 21893484
TI  - Soothing suffering swimmers: a systematic review of the epidemiology, diagnosis,
      treatment and rehabilitation of musculoskeletal injuries in competitive swimmers.
AB  - BACKGROUND: This review details the examination, diagnosis, treatment and
      management of injuries encountered by competitive swimmers. Primarily, these
      involve the shoulder, however, the spine, knee and hip can be involved. Using the
      Coleman methodology score, we show that the methods used in obtaining and
      reporting clinical findings and intervention results could be improved. Where
      possible, we suggest improvements. SOURCES OF DATA: A literature review was
      conducted in English, Italian, French and German using PubMed, Google Scholar and
      Ovid search engines with strict inclusion/exclusion criteria. AREAS OF AGREEMENT:
      Poor technique, and high training intensity and distance are the most common
      cause of missed swim practice and competition through injury. AREAS OF
      CONTROVERSY: Few articles agree on a single method of each of clinical
      examination, diagnosis, treatment and rehabilitation. GROWING POINTS: Articles
      are consistently retrospective with few investigating spine, hip and knee
      injuries. AREAS TIMELY FOR DEVELOPING RESEARCH: Clinical findings and
      rehabilitation methods should be reported using a more structured method possibly
      based on the Coleman methodological scoring system.

PMID- 21893485
TI  - Intracardiac emboli as first presentation of cardiac AL amyloidosis.

PMID- 21893486
TI  - Current concepts on coronary revascularization in diabetic patients.
AB  - Diabetic mellitus (DM) patients with coronary artery disease (CAD) are at higher
      risk of cardiovascular events compared with non-DM individuals. While aggressive
      cardiovascular prevention and adequate blood glucose control remain cornerstones
      of therapy, the decision when and how to proceed to coronary revascularization in
      an individual DM patient should be based on the extent of CAD, ischaemic burden,
      ventricular function, as well as comorbidities. While in patients with stable
      symptoms, moderate CAD on coronary angiography and preserved left ventricular
      function a conservative strategy may be a valuable initial strategy, in patients
      with acute coronary syndromes (ACS) an early invasive approach should be
      favoured. The revascularization strategy for DM patients with complex multivessel
      CAD should be discussed within a heart team consisting of cardiologists, cardiac
      surgeons, and anaesthesiologists. In general, the threshold for coronary artery
      bypass surgery (CABG) should be lower for DM than for non-DM individuals. In
      patients undergoing percutaneous coronary intervention, the use of drug-eluting
      stents (DES) and--in the setting of ACS--of potent platelet inhibitors, such as
      prasugrel or ticagrelor, should be favoured. In the near future, multiple
      strategies may further favourably impact the prognosis of DM patients undergoing
      coronary revascularization. These include alternative antiplatelet agents such as
      thromboxane receptor inhibitors, the broad use of second generation DES, and
      possibly the implantation of bioresorbable stents. Coronary artery bypass surgery
      outcomes may also further improve by wide implementation of arterial
      revascularization, reduction in perioperative stroke by avoiding clamping of the
      aorta, reduction in wound infection by minimally invasive techniques, and
      optimization of post-operative medical management.

PMID- 21893487
TI  - Rates of downstream invasive coronary angiography and revascularization: computed
      tomographic coronary angiography vs. Tc-99m single photon emission computed
      tomography.
AB  - AIMS: Computed tomographic coronary angiography (CTA) appears to be a useful
      modality for the detection of obstructive coronary artery disease (CAD). Recent
      data suggest that CTA may reduce the frequency of normal invasive coronary
      angiograms. However, there remains concern that the implementation of CTA could
      increase referrals to invasive coronary angiography (ICA). To further support the
      clinical acceptance of CTA, it is important to compare CTA to another accepted
      modality such as single photon emission computed tomography (SPECT). We followed
      a cohort of 64-slice CTA patients and a matched cohort of Tc-99m SPECT patients
      to determine downstream referrals for ICA and revascularization. METHODS AND
      RESULTS: Consecutive CTA patients (without history of revascularization or
      cardiac transplantation) were prospectively enrolled and compared with a Tc-99m
      SPECT cohort (matched for age, gender, and Morise score). Each CTA and SPECT was
      evaluated for obstructive CAD and patients were followed for downstream ICA and
      revascularization. Of the 1221 patients in each cohort, 129 (10.6%) CTA patients
      and 125 (10.2%) SPECT patients were referred to ICA. Of those referred to ICA,
      obstructive CAD was confirmed in 105 (81.4%) CTA patients and in 88 (70.4%) SPECT
      patients. Differences in false positive rates were significantly lower in the CTA
      than the SPECT cohort (9.7 and 25.8%, respectively, P = 0.009). Rates of
      revascularization were similar in the CTA and SPECT cohorts (6.2 vs. 5.9%,
      respectively). CONCLUSION: Compared with SPECT, CTA had similar referrals for ICA
      and revascularization rates but lower false positive rates. Computed tomographic
      coronary angiography appears to be a viable non-invasive diagnostic modality and
      does not appear to negatively impact upon ICA resources.

PMID- 21893488
TI  - Normal chest radiograph and ground glass opacities on a thoracic computed
      tomographic scan in a patient with diffuse alveolar haemorrhage due to dual
      antiplatelet therapy prescribed after patent foramen ovale percutaneous device
      closure.

PMID- 21893489
TI  - Acute pulmonary vasodilator response in paediatric and adult pulmonary arterial
      hypertension: occurrence and prognostic value when comparing three response
      criteria.
AB  - AIMS: To assess the occurrence and prognostic value of acute vasodilator response
      (AVR) in paediatric vs. adult pulmonary arterial hypertension, and
      idiopathic/hereditary pulmonary arterial hypertension (iPAH/HPAH) vs. pulmonary
      arterial hypertension associated with congenital heart disease (PAH-CHD) using
      three different response criteria. METHODS AND RESULTS: Ninety-nine PAH patients
      underwent AVR testing (37 children, 62 adults; 70 iPAH/HPAH, 29 PAH-CHD). Three
      response criteria from clinical practice were used to define AVR. The number of
      responders was evaluated separately in subgroups based on age, diagnosis, and
      presence of a non-restrictive post-tricuspid shunt. Numbers of responders varied
      importantly using the different criteria but were always higher in iPAH/HPAH,
      compared with PAH-CHD. The number of responders did not differ between paediatric
      and adult iPAH/HPAH. No responders were identified in patients with a post
      tricuspid shunt. Acute vasodilator response was associated with improved survival
      using all three criteria. Low baseline mean right atrial pressure (mRAP) was
      associated with improved survival in adults (P< 0.001). High baseline mean
      pulmonary arterial pressure (mPAP)/mean systemic arterial pressure (mSAP) and
      pulmonary vascular resistance (PVR)/systemic vascular resistance (SVR) were
      associated with worse survival, statistically independent from age, diagnosis,
      and the presence of a post-tricuspid shunt. CONCLUSION: The proportion of
      patients with AVR highly depends on the used criteria, but did not differ between
      paediatric and adult iPAH/HPAH. Current response criteria are not suitable for
      patients with a post-tricuspid shunt. In both children and adults without post
      tricuspid shunts, AVR was associated with improved survival independent of the
      used criteria. Nevertheless, prognostic value in the individual patient was
      limited. Baseline mRAP showed a good correlation with survival for adult PAH
      patients, but not for children. High baseline mPAP/mSAP and PVR/SVR was
      associated with worse prognosis independent from age, diagnosis, or the presence
      of a post-tricuspid shunt.

PMID- 21893490
TI  - Association of cerebral blood flow with the development of cardiac death or
      urgent heart transplantation in patients with systolic heart failure.
AB  - AIMS: Although cerebral blood flow (CBF) is known to be low in patients with
      advanced systolic heart failure (HF), little is known of the prognostic
      significance of this observation. We investigated whether CBF might be associated
      with the development of adverse outcomes in systolic HF, and whether it might
      provide prognostic information in addition to that provided by exercise tests.
      METHODS AND RESULTS: We performed a prospective observational study involving 224
      systolic HF patients (left ventricular ejection fraction <=35%). The study
      endpoint was the occurrence of cardiac death or urgent heart transplantation.
      Global CBF was measured using radionuclide angiography. Clinical, biochemical,
      echocardiographic, and exercise data were also obtained. During follow-up (median
      36 months), 52 patients experienced death or urgent transplantation.
      Multivariable analysis showed that global CBF, the minute ventilation/carbon
      dioxide production (VE/VCO(2)) slope, New York Heart Association functional class
      >=III, symptom duration >=12 months, serum sodium, and serum creatinine were
      associated with the development of the endpoint. Patients with a CBF <35.4
      mL/min/100 g were at increased risk of death or urgent transplantation (hazard
      ratio = 2.47; 95% confidence interval, 1.35-4.52). The addition of global CBF to
      a prognostic model including the VE/VCO(2) slope increased the C-index for the
      prediction of adverse outcomes with borderline significance. CONCLUSION: Cerebral
      blood flow was associated with the development of long-term outcomes in systolic
      HF, and therefore may be useful in identifying patients suitable for heart
      transplantation. This finding is especially relevant for patients in whom
      exercise tests may not be performed sufficiently.

PMID- 21893492
TI  - Maternal mortality and Millennium Development Goal 5.
AB  - INTRODUCTION: The maternal mortality ratio (MMR) is a key indicator for
      measurement of progress against Millennium Development Goal 5 (MDG 5). For many
      countries, especially those with a presumed high number of maternal deaths, only
      estimates are available. SOURCES OF DATA: Recent global estimates and the reasons
      for high maternal mortality are reviewed. AREAS OF AGREEMENT: There is
      international consensus that efforts to reduce maternal mortality globally need
      to be intensified. AREAS OF CONTROVERSY: Many countries lack accurate data on
      number of deaths in women of reproductive age and number of births. Therefore,
      statistical modelling has been used to calculate estimates, which generally have
      wide confidence intervals and may be disputed by individual countries. GROWING
      POINTS: There is renewed focus on MMR as 2015 approaches. AREAS TIMELY FOR
      DEVELOPING RESEARCH: There is a need to adapt and implement methods for measuring
      maternal mortality to generate more accurate estimates. More data on cause of
      death are needed.

PMID- 21893493
TI  - The epidemiology of thyroid disease.
AB  - INTRODUCTION: Thyroid disorders are prevalent and their manifestations are
      determined by the dietary iodine availability. SOURCES OF DATA: Data from
      screening large population samples from USA and Europe. AREAS OF AGREEMENT: The
      most common cause of thyroid disorders worldwide is iodine deficiency, leading to
      goitre formation and hypothyroidism. In iodine-replete areas, most persons with
      thyroid disorders have autoimmune disease. AREAS OF CONTROVERSY: Definition of
      thyroid disorders, selection criteria used, influence of age and sex,
      environmental factors and the different techniques used for assessment of thyroid
      function. GROWING POINTS: Increasing incidence of well-differentiated thyroid
      cancer. Environmental iodine influences the epidemiology of non-malignant thyroid
      disease. AREAS TIMELY FOR DEVELOPING RESEARCH: Iodine supplementation of
      populations with mild-to-moderate iodine deficiency. An evidence-based strategy
      for the risk stratification, treatment and follow-up of benign nodular thyroid
      disease. Is there any benefit in screening adults for thyroid dysfunction?

PMID- 21893494
TI  - Green tea gets molecular.
AB  - Green tea and its major polyphenolic flavonoid, epigallocatechin gallate (EGCG),
      have been credited with cancer chemopreventive activity for many years; the
      mechanism for this activity, however, has remained obscure. Now, as reported in
      this issue of the journal (beginning on page 1366), Urusova and colleagues showed
      direct binding of EGCG to the peptidyl prolyl cis/trans isomerase Pin1, which
      inhibited Pin1 enzymatic activity. They showed that Pin1 expression is required
      for EGCG effects on cell growth, c-Jun activation, and transcription regulation
      mediated by NF-kappaB and activator protein-1. The data provide a glimpse of the
      mechanism of action of EGCG and set a new bar for the future study of natural
      products with chemopreventive activity.

PMID- 21893495
TI  - HPV-associated Oropharyngeal Cancers--Are They Preventable?
AB  - It is not known whether a human papillomavirus (HPV)-induced oropharyngeal
      precancerous lesion could be identified by screening with a pap test equivalent
      or whether one even exists. In this issue of the journal (beginning on page
      1378), Fakhry and colleagues report their results showing that cytologic
      evaluation of the oropharynx, although useful in detecting invasive oropharyngeal
      cancers, may have limited utility as a screening modality for detecting
      precancer. These findings argue against the potential for secondary prevention of
      HPV-associated oropharyngeal cancers through screening for and preventing the
      progression of precancer and highlight the opportunity for primary prevention
      through prophylactic HPV vaccination, if proven efficacious and cost-effective.

PMID- 21893496
TI  - Brush-based cytology screening in the tonsils and cervix: there is a difference!
AB  - This perspective on the report by Fakhry and colleagues in this issue of the
      journal (beginning on page 1378) examines the diagnostic accuracy of a "Pap-test
      equivalent" for screening for human papillomavirus (HPV)-associated cancers in
      the tonsils. HPV infection is strongly associated with cancer development in the
      oropharynx (tonsils and base of tongue) and cervix; the data discussed here
      underscore the differences in screening for cervical versus oropharyngeal
      malignancies and discuss some of the challenges and limitations associated with
      screening for tonsillar premalignancy and early cancers.

PMID- 21893497
TI  - Hunting for the causes of meningioma--obesity is a suspect.
AB  - In this issue of the journal, Michaud and colleagues report a 48% increased risk
      of meningioma in obese individuals compared with individuals with a normal body
      mass index (BMI). This large prospective cohort study adds weight to the
      suggested link between BMI and meningioma, thus contributing to the growing
      number of cancer sites likely associated with body fatness. Although the exact
      mechanisms underlying the BMI-meningioma link are unclear, possible mediators
      include hormonal factors, immunologic response, and levels of insulin or insulin
      like growth factors, each of which has been implicated by various levels of
      evidence in meningioma risk. Understanding the relationships between body
      fatness, height, and hormonal and immunologic factors could provide important
      clues to the etiology of meningioma and may have implications for the early
      detection and prevention of these tumors.

PMID- 21893498
TI  - Personalizing CA125 levels for ovarian cancer screening.
AB  - Screening trials for the early detection of ovarian cancer in the general
      population and in patients at a high risk for this disease have so far failed to
      show a reduction of ovarian cancer-specific mortality. Current screening
      modalities include pelvic examinations, transvaginal ultrasounds, and cancer
      antigen 125 (CA125) serum marker levels, which are associated with a high false
      positive rate. The last decade has witnessed significant modifications in the
      interpretation of serum CA125 that extend beyond a static CA125 cutoff point. The
      Risk of Ovarian Cancer Algorithm (ROCA) incorporates changes of CA125 levels over
      time and an individual's age-specific risk. Ongoing screening trials have
      incorporated ROCA, but it is still unclear whether the algorithm will increase
      the sensitivity and specificity of early ovarian cancer diagnosis. A very recent
      study analyzed baseline CA125 serum marker levels from high-risk patients
      included in ovarian cancer screening trials conducted by the Cancer Genetics
      Network and the Gynecologic Oncology Group. The findings show that the
      distribution of CA125 serum marker levels in this population is significantly
      affected by various demographic and clinical factors, in particular menopausal
      status and oral contraceptive use in premenopausal patients. The data suggest
      that CA125 cutoff points might have to be stratified for subgroups of patients to
      reduce false-positive results. These intriguing observations will need to be
      validated in future screening trials for ovarian cancer.

PMID- 21893499
TI  - Predicting adherence to tamoxifen for breast cancer adjuvant therapy and
      prevention.
AB  - Treatment with the selective estrogen receptor modulator (SERM) tamoxifen for 5
      years has produced dramatic breast cancer-related benefits in (a) the adjuvant
      setting, with 30% to 50% reductions in recurrence, contralateral disease, and
      mortality and (b) the prevention setting of healthy high-risk women, where
      tamoxifen reduces the risk of invasive and noninvasive breast cancer by 50%.
      Despite these striking data, adherence to tamoxifen is low, and low adherence is
      associated with poor survival. Although toxicity is a major predictor of poor
      adherence after starting therapy, pretreatment (baseline) predictors of poor
      tamoxifen adherence have been minimally studied. The adherence-survival link
      underscores the critical need to identify early predictors of poor adherence, and
      recent work is beginning to address this need. A major baseline predictor of poor
      adherence to prevention is current smoking, which is interestingly absent from
      studies of adherence to adjuvant therapy. Other important prevention adherence
      factors include breast cancer risk, extremes of age, non-white ethnicity, low
      socioeconomic status, and alcohol use. The strongest adjuvant therapy predictors
      are age (especially very young), ethnicity, and socioeconomic status. Future
      studies involving prospective systematic evaluation of these and other potential
      predictors in endocrine chemoprevention (e.g., other SERMs and aromatase
      inhibitors) are critical, as is the development of effective/targeted
      interventions to improve adherence and thus treatment outcomes in at-risk women.

PMID- 21893500
TI  - Large prospective study of ovarian cancer screening in high-risk women: CA125 cut
      point defined by menopausal status.
AB  - Previous screening trials for early detection of ovarian cancer in postmenopausal
      women have used the standard CA125 cut-point of 35 U/mL, the 98th percentile in
      this population yielding a 2% false positive rate, whereas the same cut-point in
      trials of premenopausal women results in substantially higher false positive
      rates. We investigated demographic and clinical factors predicting CA125
      distributions, including 98th percentiles, in a large population of high-risk
      women participating in two ovarian cancer screening studies with common
      eligibility criteria and screening protocols. Baseline CA125 values and clinical
      and demographic data from 3,692 women participating in screening studies
      conducted by the National Cancer Institute-sponsored Cancer Genetics Network and
      Gynecologic Oncology Group were combined for this preplanned analysis. Because of
      the large effect of menopausal status on CA125 levels, statistical analyses were
      conducted separately in pre- and postmenopausal subjects to determine the impact
      of other baseline factors on predicted CA125 cut-points on the basis of 98th
      percentile. The primary clinical factor affecting CA125 cut-points was menopausal
      status, with premenopausal women having a significantly higher cut-point of 50
      U/mL, while in postmenopausal subjects the standard cut-point of 35 U/mL was
      recapitulated. In premenopausal women, current oral contraceptive (OC) users had
      a cut-point of 40 U/mL. To achieve a 2% false positive rate in ovarian cancer
      screening trials and in high-risk women choosing to be screened, the cut-point
      for initial CA125 testing should be personalized primarily for menopausal status
      (50 for premenopausal women, 40 for premenopausal on OC, and 35 for
      postmenopausal women).

PMID- 21893501
TI  - Silent acute gastric dilatation due to Salmonella infection in a diabetic
      elderly.
AB  - Acute gastric dilatation is a potentially life-threatening entity that has been
      reported in patients with some acute infections like pneumonia and staphylococcal
      bacteremia. We describe a case of acute gastric dilatation presenting atypically
      in a 65-year-old diabetic with Salmonella diarrhoea. By the fourth day of
      hospital admission the patient's abdomen was distended in the absence of pain,
      nausea or vomiting. An abdominal radiograph showed marked gastric dilatation with
      no evidence of obstruction or ileus. With nasogastric tube insertion and
      initiation of intravenous antibiotics, the stomach was back to normal size. It is
      likely that Salmonella infection was the major cause of acute gastric dilatation
      in this patient.

PMID- 21893502
TI  - Measures of everyday competence in older adults with cognitive impairment: a
      systematic review.
AB  - BACKGROUND: The issue of safety of the cognitively impaired elderly people living
      alone has been continuously raised. Traditional psychometric measures of
      cognitive abilities may not adequately reflect older adults' functioning in a
      real everyday context. OBJECTIVES: To conduct a systematic review on instruments
      available for evaluating the everyday problem-solving or everyday competence of
      the elderly with cognitive impairment and to critically review the measurement
      properties of the identified instruments. METHODS: We searched the databases such
      as Cinahl, Medline, PsycINFO, AARP Ageline, ProQuest and the Cochrane Library for
      the time period between January 1995 and December 2010. Reference lists of the
      included papers were also manually searched. RESULTS: Five instruments were
      included. All the instruments focused their framework on Instrumental Activities
      of Daily Living (IADL) domains which meet well with suggestions from other
      studies on the importance of IADL in determining an elderly individual's
      capability to live independently in the community. No available instruments for
      the moderate to severe impairment group were identified under this review.
      CONCLUSIONS: Few existing instruments to assess the ability of everyday problem
      solving of the elderly with cognitive impairment can be identified in the
      literature. Further research validating them against functional, real-world
      outcomes is needed.

PMID- 21893503
TI  - Are characteristics of the school district associated with active transportation
      to school in Danish adolescents?
AB  - BACKGROUND: This study sought to determine the influence of individual factors on
      active transportation to school among Danish seventh graders and whether school
      district factors are associated with such behaviour independently of individual
      factors. METHODS: Mixed effects logistic regression models determined the effects
      of individual (gender, family affluence, enjoyment of school and academic
      performance) and school district factors (educational level, household savings,
      land use and size) on active transportation to school (by foot, bicycle or other
      active means) among 10 380 pupils aged 13-15 years nested in 407 school
      districts. RESULTS: Of all students, 64.4% used active transportation to school
      daily. Boys, those with perceived higher school performance and those with lower
      family affluence were more likely to use active transportation to school. After
      adjustment for all individual factors listed above, high household savings at the
      school district level was associated with higher odds of active transportation to
      school. As factors of land use, low level of farming land use and high proportion
      of single houses were associated with active transportation to school.
      CONCLUSIONS: Policies aiming at reducing social inequalities at the school
      district level may enhance active transportation to school. School districts with
      farming land use face barriers for active transportation to school, requiring
      special policy attention.

PMID- 21893504
TI  - Predicting the future prevalence of cigarette smoking in Italy over the next
      three decades.
AB  - BACKGROUND: Smoking prevalence in Italy decreased by 37% from 1980 to now. This
      is due to changes in smoking initiation and cessation rates and is in part
      attributable to the development of tobacco control policies. This work aims to
      estimate the age- and sex-specific smoking initiation and cessation probabilities
      for different time periods and to predict the future smoking prevalence in Italy,
      assuming different scenarios. METHODS: A dynamic model describing the evolution
      of current, former and never smokers was developed. Cessation and relapse rates
      were estimated by fitting the model with smoking prevalence in Italy, 1986-2009.
      The estimated parameters were used to predict prevalence, according to scenarios:
      (1) 2000-09 initiation/cessation; (2) half initiation; (3) double cessation; (4)
      Scenarios 2+3; (5) triple cessation; and (6) Scenarios 2+5. RESULTS: Maintaining
      the 2000-09 initiation/cessation, the 10% goal will not be achieved within next
      three decades: prevalence will stabilize at 12.1% for women and 20.3% for men.
      The goal could be rapidly achieved for women by halving initiation and tripling
      cessation (9.9%, 2016), or tripling cessation only (10.4%, 2017); for men halving
      initiation and tripling cessation (10.8%, 2024), or doubling cessation and
      halving initiation (10.5%, 2033), or tripling cessation only (10.8%, 2033).
      CONCLUSION: The 10% goal will be achieved within the next few decades, mainly by
      increasing smoking cessation. Policies to reach this goal would include
      increasing cigarette taxes, introducing total reimbursement of smoking cessation
      treatment, with a further development of quitlines and smoking cessation
      services. These measures are not yet fully implemented in Italy.

PMID- 21893505
TI  - Perceived discrimination outside health care settings and health care utilization
      of Turkish and Moroccan GP patients in the Netherlands.
AB  - BACKGROUND: Problematic interethnic relationships, expressed by feelings of
      discrimination, may contribute to ethnic variations in health and health care
      utilization. The impact of daily perceived discrimination on (mental) health has
      been shown. Less is known about the effect of everyday discrimination on the
      health care utilization. We examined the relationship between perceived
      discrimination of Turkish and Moroccan patients on GP health care utilization in
      the Netherlands and on health services use in the home country. METHODS: Cohort
      study within the second Dutch National Survey of General Practice (2001).
      Interviews were conducted with 416 Turkish and 381 Moroccan respondents, and
      repeated in 2005 among respectively 118 and 102 participants. Linear, logistic
      and zero-inflated binomial regression models were used for the analyses. RESULTS:
      Perceived discrimination was associated with non-attendance to the GP. Perceived
      quality of GP care was not a mediator in this relationship. No evidence was found
      for substitution of health care utilization in the home country to health care in
      the host country. GP attenders had higher odds of using health care in the home
      country than non-attenders. Over time, a lasting discrimination feeling was
      related to persistent non-attendance at the GP practice. CONCLUSION: Ethnic
      minority patients who feel discriminated may avoid GP health care. Further
      research is warranted on magnitude and health effects of such potential
      underutilization. Information on perceived discrimination within health care
      settings would increase insight into the profile of non-attenders, and on
      possible measures to better target interventions at a group at risk of
      underutilization.

PMID- 21893506
TI  - Good friends, high income or resilience? What matters most for elderly patients?
AB  - BACKGROUND: Chronically ill patients need to adapt to their impaired life
      condition. Social (e.g. social support), material (e.g. income) and personal
      (e.g. mastery) resources are needed to cope with this challenge. It is, however,
      less clear whether these factors also contribute to 'relatively successful
      functioning' and whether these effects are disease specific or generic across
      chronic diseases. METHODS: Baseline data from 361 Dutch men and women aged>=60
      years who were mildly depressed and diagnosed with type 2 diabetes or chronic
      obstructive pulmonary disease (COPD) were used. These persons participated in the
      'Depression in Elderly with Long-Term Afflictions' (DELTA) study. Logistic
      regression analyses were used to study the independent association of social
      support, income and mastery (independent variables) with physical, mental and
      social functioning (dependent variables). RESULTS: A high level of mastery is
      significantly associated with physical, mental and social functioning in the
      total study population, as well as in subgroups of patients with COPD or
      diabetes. This relationship remained significant after controlling for
      confounding factors such as gender, age, educational level and the other
      remaining resources. In diabetes patients, high levels of social support and
      income also contributed significantly to successful social functioning.
      CONCLUSION: Our findings suggest that rather than having good friends and a high
      income, having a high level of mastery (resilience) might best help chronically
      ill patients in coping with and adapting to their often co-morbid condition.
      Further longitudinal research is necessary to unravel the long-term effects of
      mastery, income and social support on 'relatively successful functioning' in
      chronically ill patients.

PMID- 21893507
TI  - Parental education as a predictor of offspring behavioural and physiological
      cardiovascular disease risk factors.
AB  - BACKGROUND: Childhood socio-economic disadvantage has been shown to be associated
      with an elevated rate of cardiovascular disease (CVD) events in adulthood. The
      objective of this study is to examine associations between mothers' and fathers'
      education and offspring CVD risk factors. METHODS: The Oslo Youth Study (n = 498)
      was initiated in 1979. Children (age 11-15 years) attending six schools and their
      parents were included. Information on education was collected for parents and
      participants. Participants were followed through 2006 (age 40 years). Information
      about physical activity, diet, smoking, binge drinking, body mass index (BMI), s
      cholesterol, s-triglycerides and blood pressure was collected in 1981, 1991 and
      2006. RESULTS: Fathers' education was inversely associated with participants' BMI
      at 15 and 25 years, cholesterol at 25 and 40 years, triglycerides at 25 years and
      systolic blood pressure at 15 and 25 years (regression coefficients -0.18 to 
      0.11; P < 0.05 for all). The effects were weakened after adjusting for
      participants' own education. Maternal education showed no association with these
      risk factors. After controlling for participants' own education, associations
      between parental education and behavioural risk factors in adulthood were few.
      CONCLUSION: Any impact of parental education on offspring CVD risk factors seemed
      to be mediated via subject's own education. Parental education offered little
      predictive capacity for offspring CVD risk factors.

PMID- 21893508
TI  - Therapeutic approach for patients with catecholaminergic polymorphic ventricular
      tachycardia: state of the art and future developments.
AB  - Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited
      arrhythmia syndrome characterized by bidirectional or polymorphic ventricular
      arrhythmias under conditions of increased sympathetic activity in young patients
      with structurally normal hearts. Patients with CPVT are at high risk of
      developing life-threatening ventricular arrhythmias when untreated. A wide
      variety of arrhythmic event rates on conventional therapy, with beta-blockers as
      the cornerstone, has been reported. Here, we systematically review all available
      studies describing the efficacy of beta-blocker therapy for prevention of
      arrhythmic events in CPVT. Because of heterogeneity between the studies, a random
      effects meta-analysis model was used to assess the efficacy of beta-blocker
      therapy in preventing any arrhythmic event [syncope, aborted cardiac arrest
      (ACA), and sudden cardiac death (SCD)], near-fatal arrhythmic events (ACA and
      SCD), and fatal arrhythmic events. Eleven studies including 403 patients, of whom
      354 (88%) had a beta-blocker prescribed, were identified. Mean follow-up ranged
      from 20 months to 8 years. Estimated 8-year arrhythmic, near-fatal, and fatal
      event rates were 37.2% [95% confidence interval (CI): 16.6-57.7], 15.3% (95% CI:
      7.4-23.3), and 6.4% (95% CI: 3.2-9.6), respectively. In addition, we review the
      recent developments in alternate chronic treatment options for CPVT patients,
      including calcium channel blockers, flecainide, left cardiac sympathetic
      denervation, and implantable cardioverter defibrillators. A new treatment
      strategy is proposed, including a stepwise addition of the alternate treatment
      options to beta-blockers in patients who do not respond sufficiently to this
      first-line therapy. Finally, future developments in chronic treatment options and
      acute treatment options of ventricular arrhythmias are discussed.

PMID- 21893509
TI  - Dreaming of a 'Swiss Army Knife' for atrial fibrillation ablation ...

PMID- 21893510
TI  - Successful ablation of sinus node reentrant tachycardia using remote magnetic
      navigation system.
AB  - Ablation of sinus node reentrant tachycardia (SNRT) may be difficult with risk of
      sinus node injury by using conventional catheters. We report successful ablation
      of SNRT by using remote magnetic navigation system (Stereotaxis).

PMID- 21893511
TI  - Reduced fluoroscopy exposure during ablation of atrial fibrillation using a novel
      electroanatomical navigation system: a multicentre experience.
AB  - AIMS: Catheter ablation of atrial fibrillation (AF) focuses on pulmonary vein
      (PV) ablation with or without additional atrial substrate modification. These
      procedures require significant fluoroscopy exposure. A new 3D non-fluoroscopic
      navigation system (CARTO((r)) 3 System, Biosense Webster, CA, USA) that allows
      precise location visualization of diagnostic and ablation catheters was evaluated
      for its impact on fluoroscopic exposure during AF ablation procedures. METHODS
      AND RESULTS: Two groups of patients were treated by our centres for drug
      refractory AF. One group was treated using the new CARTO((r)) 3 system to guide
      catheter ablation (Group A, 117 patients). The other group was treated using the
      CARTO((r)) XP system (Biosense Webster) 3 months previously (Group B, 123
      patients). For both groups, circumferential PV ostia ablation was performed; PV
      isolation was validated using a circular catheter placed at each ostium. There
      was no difference in any clinical characteristics (age, sex, AF type, left atrium
      diameter and volume, and heart disease) among the two study groups. The mean
      number of PVs identified and isolated per patient was similar in both groups, as
      were the mean procedural duration and radiofrequency time. However, mean
      fluoroscopic time was significantly reduced in Group A (15.9+/-12.3 min) as
      compared with Group B (26+/-15.1 min) (P < 0.001). CONCLUSION: This multicentre
      observational study demonstrates a significant reduction of fluoroscopy exposure
      using a new 3D non-fluoroscopic mapping system to guide AF catheter ablation.

PMID- 21893512
TI  - Histological findings around electrodes in pacemaker and implantable cardioverter
      defibrillator patients: comparison of steroid-eluting and non-steroid-eluting
      electrodes.
AB  - AIMS: To analyse histological findings surrounding the electrodes in
      pacemaker/implantable cardioverter-defibrillator (PM/ICD) patients. To compare
      histology around steroid-eluting and non-steroid ventricular pacing electrodes.
      METHODS AND RESULTS: In autopsied PM/ICD patients histopathological findings
      around the electrodes were determined. Seventy patients were studied, PM(58),
      ICD(12), mean age 75.1 +/- 9.3 years. The implantation-death interval was 4.0 +/-
      3.3 years. Most causes of death were cardiac (PM 52%, ICD 58%). The majority of
      atrial electrodes were attached to the endocardium and most ventricular
      electrodes were found in the myocardium (P <= 0.001). The maximum thickness of
      the fibrous electrode sheath was greatest for the ICD ventricular electrodes.
      Some electrodes were covered with fibrin thrombi and granulation tissue, most
      frequently in the ICD ventricular electrodes. The fibrous sheath usually
      contained chronic inflammatory cells and in some cases particles of foreign
      material, foreign body giant cells, and haematogenous pigment. The tissue around
      steroid-eluting ventricle PM electrodes was compared with the tissue around the
      non-steroid-eluting ventricle PM electrodes; granulation tissue, foreign
      material, giant cells being found more frequently around the steroid-eluting
      electrodes. The fibrous sheath was slightly thinner in the steroid-eluting
      electrodes. The histology around four coronary sinus electrodes was described.
      CONCLUSIONS: Atrial electrodes were attached more superficially to the
      endocardium while PM and ICD ventricular electrodes were more frequently embedded
      in the myocardium. The electrodes were covered by a connective tissue sheath as a
      result of thrombus organization. This process persisted most frequently around
      ICD ventricular electrodes. Only borderline differences were found between the
      histological findings around steroid-eluting and non-steroid-eluting PM
      ventricular electrodes.

PMID- 21893513
TI  - Golgi body motility in the plant cell cortex correlates with actin cytoskeleton
      organization.
AB  - The actin cytoskeleton is involved in the transport and positioning of Golgi
      bodies, but the actin-based processes that determine the positioning and motility
      behavior of Golgi bodies are not well understood. In this work, we have studied
      the relationship between Golgi body motility behavior and actin organization in
      intercalary growing root epidermal cells during different developmental stages.
      We show that in these cells two distinct actin configurations are present,
      depending on the developmental stage. In small cells of the early root elongation
      zone, fine filamentous actin (F-actin) occupies the whole cell, including the
      cortex. In larger cells in the late elongation zone that have almost completed
      cell elongation, actin filament bundles are interspersed with areas containing
      this fine F-actin and areas without F-actin. Golgi bodies in areas with the fine
      F-actin exhibit a non-directional, wiggling type of motility. Golgi bodies in
      areas containing actin filament bundles move up to 7 MUm s-1. Since the motility
      of Golgi bodies changes when they enter an area with a different actin
      configuration, we conclude that the type of movement depends on the actin
      organization and not on the individual organelle. Our results show that the
      positioning of Golgi bodies depends on the local actin organization.

PMID- 21893514
TI  - Characterization of Arabidopsis CTP:3-deoxy-D-manno-2-octulosonate
      cytidylyltransferase (CMP-KDO synthetase), the enzyme that activates KDO during
      rhamnogalacturonan II biosynthesis.
AB  - In plant cells, boron (B) occurs predominantly as a borate ester associated with
      rhamnogalacturonan II (RG-II), but the function of this B-RG-II complex has yet
      to be investigated. 3-Deoxy-D-manno-2-octulosonic acid (KDO) is a specific
      component monosaccharide of RG-II. Mutant plants defective in KDO biosynthesis
      are expected to have altered RG-II structure, and would be useful for studying
      the physiological function of the B-RG-II complex. Here, we characterized
      Arabidopsis CTP:KDO cytidylyltransferase (CMP-KDO synthetase; CKS), the enzyme
      activating KDO as a nucleotide sugar prior to its incorporation into RG-II. Our
      analyses localized the Arabidopsis CKS protein to mitochondria. The Arabidopsis
      CKS gene occurs as a single-copy gene in the genome, and we could not obtain cks
      null mutants from T-DNA insertion lines. Analysis using +/cks heterozygotes in
      the quartet1 background demonstrated that the cks mutation rendered pollen
      infertile through the inhibition of pollen tube elongation. These results suggest
      that KDO is an indispensable component of RG-II, and that the complete B-RG-II
      complex is essential for the cell wall integrity of rapidly growing tissues.

PMID- 21893515
TI  - Mannitol transport and mannitol dehydrogenase activities are coordinated in Olea
      europaea under salt and osmotic stresses.
AB  - The intracellular accumulation of organic compatible solutes functioning as
      osmoprotectants, such as polyols, is an important response mechanism of several
      plants to drought and salinity. In Olea europaea a mannitol transport system
      (OeMaT1) was previously characterized as a key player in plant response to
      salinity. In the present study, heterotrophic sink models, such as olive cell
      suspensions and fruit tissues, and source leaves were used for analytical,
      biochemical and molecular studies. The kinetic parameters of mannitol
      dehydrogenase (MTD) determined in cells growing in mannitol, at 25 degrees C and
      pH 9.0, were as follows: K(m), 54.5 mM mannitol; and V(max), 0.47 MUmol h-1 mg-1
      protein. The corresponding cDNA was cloned and named OeMTD1. OeMTD1 expression
      was correlated with MTD activity, OeMaT1 expression and carrier-mediated mannitol
      transport in mannitol- and sucrose-grown cells. Furthermore, sucrose-grown cells
      displayed only residual OeMTD activity, even though high levels of OeMTD1
      transcription were observed. There is evidence that OeMTD is regulated at both
      transcriptional and post-transcriptional levels. MTD activity and OeMTD1
      expression were repressed after Na+, K+ and polyethylene glycol (PEG) treatments,
      in both mannitol- and sucrose-grown cells. In contrast, salt and drought
      significantly increased mannitol transport activity and OeMaT1 expression. Taken
      together, these studies support that olive trees cope with salinity and drought
      by coordinating mannitol transport with intracellular metabolism.

PMID- 21893516
TI  - Comparison of human blood concentrations of collectin kidney 1 and mannan-binding
      lectin.
AB  - Mannan-binding lectin (MBL) was first discovered as a collectin in animal blood,
      and was shown to have such unique characteristics as a collage-like domain and a
      carbohydrate recognition domain. We recently identified human collectin kidney 1
      (CL-K1, COLEC11) from a human kidney cDNA library. To quantitate the CL-K1
      concentration in blood, we developed several polyclonal and monoclonal antibodies
      using recombinant human CL-K1 in CHO cells and the CL-K1 fragment in Escherichia
      coli. Using these antibodies, we established a sandwich enzyme-linked
      immunosorbent assay (ELISA) system. The concentration of CL-K1 in human plasma
      was 0.34 +/- 0.13 ug/ml and that in MBL was 1.72 +/- 1.51 ug/ml. Concentrations
      of MBL are often low due to its single nucleotide polymorphisms (SNPs) which seem
      to be related to an opsonic defect. However, no low concentrations of CL-K1 were
      observed on testing over two hundred blood samples. We also found that the blood
      concentration of CL-K1 was not dependent on gender or age and did not correlate
      completely with that of MBL. The ELISA system developed in this study will be
      useful for elucidating the physiological and pathophysiological role of CL-K1 in
      humans.

PMID- 21893517
TI  - Gaussian interaction profile kernels for predicting drug-target interaction.
AB  - MOTIVATION: The in silico prediction of potential interactions between drugs and
      target proteins is of core importance for the identification of new drugs or
      novel targets for existing drugs. However, only a tiny portion of all drug-target
      pairs in current datasets are experimentally validated interactions. This
      motivates the need for developing computational methods that predict true
      interaction pairs with high accuracy. RESULTS: We show that a simple machine
      learning method that uses the drug-target network as the only source of
      information is capable of predicting true interaction pairs with high accuracy.
      Specifically, we introduce interaction profiles of drugs (and of targets) in a
      network, which are binary vectors specifying the presence or absence of
      interaction with every target (drug) in that network. We define a kernel on these
      profiles, called the Gaussian Interaction Profile (GIP) kernel, and use a simple
      classifier, (kernel) Regularized Least Squares (RLS), for prediction drug-target
      interactions. We test comparatively the effectiveness of RLS with the GIP kernel
      on four drug-target interaction networks used in previous studies. The proposed
      algorithm achieves area under the precision-recall curve (AUPR) up to 92.7,
      significantly improving over results of state-of-the-art methods. Moreover, we
      show that using also kernels based on chemical and genomic information further
      increases accuracy, with a neat improvement on small datasets. These results
      substantiate the relevance of the network topology (in the form of interaction
      profiles) as source of information for predicting drug-target interactions.
      AVAILABILITY: Software and Supplementary Material are available at
      http://cs.ru.nl/~tvanlaarhoven/drugtarget2011/. CONTACT: tvanlaarhoven@cs.ru.nl;
      elenam@cs.ru.nl. SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 21893518
TI  - SiTaR: a novel tool for transcription factor binding site prediction.
AB  - MOTIVATION: Prediction of transcription factor binding sites (TFBSs) is crucial
      for promoter modeling and network inference. Quality of the predictions is
      spoiled by numerous false positives, which persist as the main problem for all
      presently available TFBS search methods. RESULTS: We suggest a novel approach,
      which is alternative to widely used position weight matrices (PWMs) and Hidden
      Markov Models. Each motif of the input set is used as a search template to scan a
      query sequence. Found motifs are assigned scores depending on the non-randomness
      of the motif's occurrence, the number of matching searching motifs and the number
      of mismatches. The non-randomness is estimated by comparison of observed numbers
      of matching motifs with those predicted to occur by chance. The latter can be
      calculated given the base compositions of the motif and the query sequence. The
      method does not require preliminary alignment of the input motifs, hence avoiding
      uncertainties introduced by the alignment procedure. In comparison with PWM-based
      tools, our method demonstrates higher precision by the same sensitivity and
      specificity. It also tends to outperform methods combining pattern and PWM
      search. Most important, it allows reducing the number of false positive
      predictions significantly. AVAILABILITY: The method is implemented in a tool
      called SiTaR (Site Tracking and Recognition) and is available at http://sbi.hki
      jena.de/sitar/index.php. CONTACT: ekaterina.shelest@hki-jena.de SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 21893519
TI  - Integrated pathway-level analysis of transcriptomics and metabolomics data with
      IMPaLA.
AB  - SUMMARY: Pathway-level analysis is a powerful approach enabling interpretation of
      post-genomic data at a higher level than that of individual biomolecules. Yet, it
      is currently hard to integrate more than one type of omics data in such an
      approach. Here, we present a web tool 'IMPaLA' for the joint pathway analysis of
      transcriptomics or proteomics and metabolomics data. It performs over
      representation or enrichment analysis with user-specified lists of metabolites
      and genes using over 3000 pre-annotated pathways from 11 databases. As a result,
      pathways can be identified that may be disregulated on the transcriptional level,
      the metabolic level or both. Evidence of pathway disregulation is combined,
      allowing for the identification of additional pathways with changed activity that
      would not be highlighted when analysis is applied to any of the functional levels
      alone. The tool has been implemented both as an interactive website and as a web
      service to allow a programming interface. AVAILABILITY: The web interface of
      IMPaLA is available at http://impala.molgen.mpg.de. A web services programming
      interface is provided at http://impala.molgen.mpg.de/wsdoc. CONTACT:
      kamburov@molgen.mpg.de; r.cavill@imperial.ac.uk; h.keun@imperial.ac.uk
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 21893520
TI  - Semi-supervised learning improves gene expression-based prediction of cancer
      recurrence.
AB  - MOTIVATION: Gene expression profiling has shown great potential in outcome
      prediction for different types of cancers. Nevertheless, small sample size
      remains a bottleneck in obtaining robust and accurate classifiers. Traditional
      supervised learning techniques can only work with labeled data. Consequently, a
      large number of microarray data that do not have sufficient follow-up information
      are disregarded. To fully leverage all of the precious data in public databases,
      we turned to a semi-supervised learning technique, low density separation (LDS).
      RESULTS: Using a clinically important question of predicting recurrence risk in
      colorectal cancer patients, we demonstrated that (i) semi-supervised
      classification improved prediction accuracy as compared with the state of the art
      supervised method SVM, (ii) performance gain increased with the number of
      unlabeled samples, (iii) unlabeled data from different institutes could be
      employed after appropriate processing and (iv) the LDS method is robust with
      regard to the number of input features. To test the general applicability of this
      semi-supervised method, we further applied LDS on human breast cancer datasets
      and also observed superior performance. Our results demonstrated great potential
      of semi-supervised learning in gene expression-based outcome prediction for
      cancer patients. CONTACT: bing.zhang@vanderbilt.edu. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 21893521
TI  - Distribution, enrichment and principal component analysis for possible sources of
      naturally occurring and anthropogenic radionuclides in the agricultural soil of
      Punjab state, India.
AB  - Enrichment factor (EF) of elements including geo-accumulation indices for soil
      quality and principal component analysis (PCA) were used to identify the
      contributions of the origin of sources in the studied area. Results of (40)K,
      (137)Cs, (238)U and (232)Th including their decay series isotopes in the
      agricultural soil of Mansa and Bathinda districts in the state of Punjab were
      presented and discussed. The measured mean radioactivity concentrations for
      (238)U, (232)Th and (40)K in the agricultural soil of the studied area differed
      from nationwide average crustal abundances by 51, 17 and 43 %, respectively. The
      sequence of the EFs of radionuclides in soil from the greatest to the least was
      found to be (238)U > (40)K > (226)Ra > (137)Cs > (232)Th > (228)Ra. Even though
      the enrichment of naturally occurring radionuclides was found to be higher, they
      remained to be in I(geo) class of '0', indicating that the soil is uncontaminated
      with respect to these radionuclides. Among non-metals, N showed the highest EF
      and belonged to I(geo) class of '2', indicating that soil is moderately
      contaminated due to intrusion of fertiliser. The resulting data set of elemental
      contents in soil was also interpreted by PCA, which facilitates identification of
      the different groups of correlated elements. The levels of the (40)K, (238)U and
      (232)Th radionuclides showed a significant positive correlation with each other,
      suggesting a similar origin of their geochemical sources and identical behaviour
      during transport in the soil system.

PMID- 21893522
TI  - Modelling functional trait acclimation for trees of different height in a forest
      light gradient: emergent patterns driven by carbon gain maximization.
AB  - Forest trees show large changes in functional traits as they develop from a
      sapling in the shaded understorey to an adult in the light-exposed canopy. The
      adaptive function of such changes remains poorly understood. The carbon gain
      hypothesis suggests that these changes should be adaptive (acclimation) and that
      they serve to maximize net vegetative or reproductive growth. We explore the
      carbon gain hypothesis using a mechanistic model that combines an above-ground
      plant structure, a biochemical photosynthesis model and a biophysical stomatal
      conductance model. Our simulations show how forest trees that maximize their
      carbon gain increase their total leaf area, sapwood area and leaf photosynthetic
      capacity with tree height and light intensity. In turn, they show how forest
      trees increased crown stomatal conductance and transpiration, and how the carbon
      budget was affected. These responses in functional traits to tree height (and
      light availability) largely differed from the responses exhibited by exposed
      trees. Forest and exposed trees nevertheless shared a number of emergent
      patterns: they showed a similar decrease in the average leaf water potential and
      intercellular CO(2) concentration with tree height, and kept almost constant
      values for the ratio of light absorption to electron transport capacity, the
      ratio of photosynthetic capacity to water supply capacity, and nitrogen
      partitioning between electron transport and carboxylation. While most of the
      predicted qualitative responses in individual traits are consistent with field or
      lab observations, the empirical support for capacity balances is scarce. We
      conclude that modelling functional trait optimization and carbon gain
      maximization from underlying physiological processes and trade-offs generates a
      set of predictions for functional trait acclimation and maintenance of capacity
      balances of trees of different height in a forest light gradient, but actual
      tests of the predicted patterns are still scarce.

PMID- 21893523
TI  - The sleeping brain as a complex system.
AB  - 'Complexity science' is a rapidly developing research direction with applications
      in a multitude of fields that study complex systems consisting of a number of
      nonlinear elements with interesting dynamics and mutual interactions. This Theme
      Issue 'The complexity of sleep' aims at fostering the application of complexity
      science to sleep research, because the brain in its different sleep stages adopts
      different global states that express distinct activity patterns in large and
      complex networks of neural circuits. This introduction discusses the
      contributions collected in the present Theme Issue. We highlight the potential
      and challenges of a complex systems approach to develop an understanding of the
      brain in general and the sleeping brain in particular. Basically, we focus on two
      topics: the complex networks approach to understand the changes in the functional
      connectivity of the brain during sleep, and the complex dynamics of sleep,
      including sleep regulation. We hope that this Theme Issue will stimulate and
      intensify the interdisciplinary communication to advance our understanding of the
      complex dynamics of the brain that underlies sleep and consciousness.

PMID- 21893524
TI  - Large-scale functional brain networks in human non-rapid eye movement sleep:
      insights from combined electroencephalographic/functional magnetic resonance
      imaging studies.
AB  - This paper reviews the existing body of knowledge on the neural correlates of
      spontaneous oscillations, functional connectivity and brain plasticity in human
      non-rapid eye movement (NREM) sleep. The first section reviews the evidence that
      specific sleep events as slow waves and spindles are associated with transient
      increases in regional brain activity. The second section describes the changes in
      functional connectivity during NREM sleep, with a particular focus on changes
      within a low-frequency, large-scale functional brain network. The third section
      will discuss the possibility that spontaneous oscillations and differential
      functional connectivity are related to brain plasticity and systems
      consolidation, with a particular focus on motor skill acquisition. Implications
      for the mode of information processing per sleep stage and future experimental
      studies are discussed.

PMID- 21893525
TI  - Characterizing the complexity of brain and mind networks.
AB  - Recent studies of brain connectivity and language with methods of complex
      networks have revealed common features of organization. These observations open a
      window to better understand the intrinsic relationship between the brain and the
      mind by studying how information is either physically stored or mentally
      represented. In this paper, we review some of the results in both brain and
      linguistic networks, and we illustrate how modelling approaches can serve to
      comprehend the relationship between the structure of the brain and its function.
      On the one hand, we show that brain and neural networks display dynamical
      behaviour with optimal complexity in terms of a balance between their capacity to
      simultaneously segregate and integrate information. On the other hand, we show
      how principles of neural organization can be implemented into models of memory
      storage and recognition to reproduce spontaneous transitions between memories,
      resembling phenomena of memory association studied in psycholinguistic
      experiments.

PMID- 21893526
TI  - Causal density and integrated information as measures of conscious level.
AB  - An outstanding challenge in neuroscience is to develop theoretically grounded and
      practically applicable quantitative measures that are sensitive to conscious
      level. Such measures should be high for vivid alert conscious wakefulness, and
      low for unconscious states such as dreamless sleep, coma and general anaesthesia.
      Here, we describe recent progress in the development of measures of dynamical
      complexity, in particular causal density and integrated information. These and
      similar measures capture in different ways the extent to which a system's
      dynamics are simultaneously differentiated and integrated. Because conscious
      scenes are distinguished by the same dynamical features, these measures are
      therefore good candidates for reflecting conscious level. After reviewing the
      theoretical background, we present new simulation results demonstrating
      similarities and differences between the measures, and we discuss remaining
      challenges in the practical application of the measures to empirically obtained
      data.

PMID- 21893527
TI  - Assessing interactions in the brain with exact low-resolution electromagnetic
      tomography.
AB  - Scalp electric potentials (electroencephalogram; EEG) are contingent to the
      impressed current density unleashed by cortical pyramidal neurons undergoing post
      synaptic processes. EEG neuroimaging consists of estimating the cortical current
      density from scalp recordings. We report a solution to this inverse problem that
      attains exact localization: exact low-resolution brain electromagnetic tomography
      (eLORETA). This non-invasive method yields high time-resolution intracranial
      signals that can be used for assessing functional dynamic connectivity in the
      brain, quantified by coherence and phase synchronization. However, these measures
      are non-physiologically high because of volume conduction and low spatial
      resolution. We present a new method to solve this problem by decomposing them
      into instantaneous and lagged components, with the lagged part having almost pure
      physiological origin.

PMID- 21893529
TI  - Non-homogeneous extracellular resistivity affects the current-source density
      profiles of up-down state oscillations.
AB  - Rhythmic local field potential (LFP) oscillations observed during deep sleep are
      the result of synchronized electrical activities of large neuronal ensembles,
      which consist of alternating periods of activity and silence, termed 'up' and
      'down' states, respectively. Current-source density (CSD) analysis indicates that
      the up states of these slow oscillations are associated with current sources in
      superficial cortical layers and sinks in deep layers, while the down states
      display the opposite pattern of source-sink distribution. We show here that a
      network model of up and down states displays this CSD profile only if a frequency
      filtering extracellular medium is assumed. When frequency filtering was modelled
      as inhomogeneous conductivity, this simple model had considerably more power in
      slow frequencies, resulting in significant differences in LFP and CSD profiles
      compared with the constant-resistivity model. These results suggest that the
      frequency-filtering properties of extracellular media may have important
      consequences for the interpretation of the results of CSD analysis.

PMID- 21893528
TI  - Towards a model-based integration of co-registered
      electroencephalography/functional magnetic resonance imaging data with realistic
      neural population meshes.
AB  - Brain activity can be measured with several non-invasive neuroimaging modalities,
      but each modality has inherent limitations with respect to resolution, contrast
      and interpretability. It is hoped that multimodal integration will address these
      limitations by using the complementary features of already available data.
      However, purely statistical integration can prove problematic owing to the
      disparate signal sources. As an alternative, we propose here an advanced neural
      population model implemented on an anatomically sound cortical mesh with freely
      adjustable connectivity, which features proper signal expression through a
      realistic head model for the electroencephalogram (EEG), as well as a
      haemodynamic model for functional magnetic resonance imaging based on blood
      oxygen level dependent contrast (fMRI BOLD). It hence allows simultaneous and
      realistic predictions of EEG and fMRI BOLD from the same underlying model of
      neural activity. As proof of principle, we investigate here the influence on
      simulated brain activity of strengthening visual connectivity. In the future we
      plan to fit multimodal data with this neural population model. This promises
      novel, model-based insights into the brain's activity in sleep, rest and task
      conditions.

PMID- 21893530
TI  - The thalamic low-threshold Ca2+ potential: a key determinant of the local and
      global dynamics of the slow (<1 Hz) sleep oscillation in thalamocortical
      networks.
AB  - During non-rapid eye movement sleep and certain types of anaesthesia, neurons in
      the neocortex and thalamus exhibit a distinctive slow (<1 Hz) oscillation that
      consists of alternating UP and DOWN membrane potential states and which
      correlates with a pronounced slow (<1 Hz) rhythm in the electroencephalogram.
      While several studies have claimed that the slow oscillation is generated
      exclusively in neocortical networks and then transmitted to other brain areas,
      substantial evidence exists to suggest that the full expression of the slow
      oscillation in an intact thalamocortical (TC) network requires the balanced
      interaction of oscillator systems in both the neocortex and thalamus. Within such
      a scenario, we have previously argued that the powerful low-threshold Ca(2+)
      potential (LTCP)-mediated burst of action potentials that initiates the UP states
      in individual TC neurons may be a vital signal for instigating UP states in
      related cortical areas. To investigate these issues we constructed a
      computational model of the TC network which encompasses the important known
      aspects of the slow oscillation that have been garnered from earlier in vivo and
      in vitro experiments. Using this model we confirm that the overall expression of
      the slow oscillation is intricately reliant on intact connections between the
      thalamus and the cortex. In particular, we demonstrate that UP state-related LTCP
      mediated bursts in TC neurons are proficient in triggering synchronous UP states
      in cortical networks, thereby bringing about a synchronous slow oscillation in
      the whole network. The importance of LTCP-mediated action potential bursts in the
      slow oscillation is also underlined by the observation that their associated
      dendritic Ca(2+) signals are the only ones that inform corticothalamic synapses
      of the TC neuron output, since they, but not those elicited by tonic action
      potential firing, reach the distal dendritic sites where these synapses are
      located.

PMID- 21893531
TI  - Quantitative modelling of sleep dynamics.
AB  - Arousal is largely controlled by the ascending arousal system of the hypothalamus
      and brainstem, which projects to the corticothalamic system responsible for
      electroencephalographic (EEG) signatures of sleep. Quantitative physiologically
      based modelling of brainstem dynamics theory is described here, using realistic
      parameters, and links to EEG are outlined. Verification against a wide range of
      experimental data is described, including arousal dynamics under normal
      conditions, sleep deprivation, stimuli, stimulants and jetlag, plus key features
      of wake and sleep EEGs.

PMID- 21893532
TI  - Circadian regulation of sleep-wake behaviour in nocturnal rats requires multiple
      signals from suprachiasmatic nucleus.
AB  - The dynamics of sleep and wake are strongly linked to the circadian clock. Many
      models have accurately predicted behaviour resulting from dynamic interactions
      between these two systems without specifying physiological substrates for these
      interactions. By contrast, recent experimental work has identified much of the
      relevant physiology for circadian and sleep-wake regulation, but interaction
      dynamics are difficult to study experimentally. To bridge these approaches, we
      developed a neuronal population model for the dynamic, bidirectional,
      neurotransmitter-mediated interactions of the sleep-wake and circadian regulatory
      systems in nocturnal rats. This model proposes that the central circadian
      pacemaker, located within the suprachiasmatic nucleus (SCN) of the hypothalamus,
      promotes sleep through single neurotransmitter-mediated signalling to sleep-wake
      regulatory populations. Feedback projections from these populations to the SCN
      alter SCN firing patterns and fine-tune this modulation. Although this model
      reproduced circadian variation in sleep-wake dynamics in nocturnal rats, it
      failed to describe the sleep-wake dynamics observed in SCN-lesioned rats. We thus
      propose two alternative, physiologically based models in which neurotransmitter-
      and neuropeptide-mediated signalling from the SCN to sleep-wake populations
      introduces mechanisms to account for the behaviour of both the intact and SCN
      lesioned rat. These models generate testable predictions and offer a new
      framework for modelling sleep-wake and circadian interactions.

PMID- 21893533
TI  - The multiple time scales of sleep dynamics as a challenge for modelling the
      sleeping brain.
AB  - A particular property of the sleeping brain is that it exhibits dynamics on very
      different time scales ranging from the typical sleep oscillations such as sleep
      spindles and slow waves that can be observed in electroencephalogram (EEG)
      segments of several seconds duration over the transitions between the different
      sleep stages on a time scale of minutes to the dynamical processes involved in
      sleep regulation with typical time constants in the range of hours. There is an
      increasing body of work on mathematical and computational models addressing these
      different dynamics, however, usually considering only processes on a single time
      scale. In this paper, we review and present a new analysis of the dynamics of
      human sleep EEG at the different time scales and relate the findings to recent
      modelling efforts pointing out both the achievements and remaining challenges.

PMID- 21893534
TI  - Vaccines and global health.
AB  - Vaccines have made a major contribution to global health in recent decades but
      they could do much more. In November 2011, a Royal Society discussion meeting,
      'New vaccines for global health', was held in London to discuss the past
      contribution of vaccines to global health and to consider what more could be
      expected in the future. Papers presented at the meeting reviewed recent successes
      in the deployment of vaccines against major infections of childhood and the
      challenges faced in developing vaccines against some of the world's remaining
      major infectious diseases such as human immunodeficiency virus (HIV), malaria and
      tuberculosis. The important contribution that development of more effective
      veterinary vaccines could make to global health was also addressed. Some of the
      social and financial challenges to the development and deployment of new vaccines
      were reviewed. The latter issues were also discussed at a subsequent satellite
      meeting, 'Accelerating vaccine development', held at the Kavli Royal Society
      International Centre. Delegates at this meeting considered challenges to the more
      rapid development and deployment of both human and veterinary vaccines and how
      these might be addressed. Papers based on presentations at the discussion meeting
      and a summary of the main conclusions of the satellite meeting are included in
      this issue of Philosophical Transactions of the Royal Society B.

PMID- 21893535
TI  - Contribution of the GAVI Alliance to improving health and reducing poverty.
AB  - The Global Alliance for Vaccines and Immunization (GAVI), now 10 years old, was
      established as a successful and innovative public-private partnership to deal
      with a fundamental inequity. The poorest children in the poorest parts of the
      world were being denied access to life-saving vaccines simply on the basis of
      cost. GAVI has been successful in mobilizing significant funding from donors and
      through innovative financing instruments, immunizing large numbers of children.
      GAVI has been less successful, at least in the time frames first envisaged, at
      quickly reducing the prices of new and under-used vaccines to levels affordable
      by the poorest countries. Vaccines remain some of the most cost effective of
      public health interventions. As GAVI seeks to introduce a new set of vaccines to
      tackle major killers such as pneumonia and diarrhoea, and emerging threats such
      as cervical cancer, it needs to raise significant additional funds. There is no
      single solution. Multiple and new instruments will be required to raise finance
      both globally and at the country level, and also to incentivize industry and
      others to provide vaccines at affordable prices to the poorest countries.

PMID- 21893537
TI  - Twenty-first century vaccines.
AB  - In the twentieth century, vaccination has been possibly the greatest revolution
      in health. Together with hygiene and antibiotics, vaccination led to the
      elimination of many childhood infectious diseases and contributed to the increase
      in disability-free life expectancy that in Western societies rose from 50 to 78
      85 years (Crimmins, E. M. & Finch, C. E. 2006 Proc. Natl Acad. Sci. USA 103, 498
      503; Kirkwood, T. B. 2008 Nat. Med 10, 1177-1185). In the twenty-first century,
      vaccination will be expected to eliminate the remaining childhood infectious
      diseases, such as meningococcal meningitis, respiratory syncytial virus, group A
      streptococcus, and will address the health challenges of this century such as
      those associated with ageing, antibiotic resistance, emerging infectious diseases
      and poverty. However, for this to happen, we need to increase the public trust in
      vaccination so that vaccines can be perceived as the best insurance against most
      diseases across all ages.

PMID- 21893536
TI  - Innate immunity and adjuvants.
AB  - Innate immunity was for a long time considered to be non-specific because the
      major function of this system is to digest pathogens and present antigens to the
      cells involved in acquired immunity. However, recent studies have shown that
      innate immunity is not non-specific, but is instead sufficiently specific to
      discriminate self from pathogens through evolutionarily conserved receptors,
      designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role
      in early host defence against invading pathogens. Furthermore, TLRs were found to
      act as adjuvant receptors that create a bridge between innate and adaptive
      immunity, and to have important roles in the induction of adaptive immunity. This
      paradigm shift is now changing our thinking on the pathogenesis and treatment of
      infectious, immune and allergic diseases, as well as cancers. Besides TLRs,
      recent findings have revealed the presence of a cytosolic detector system for
      invading pathogens. I will review the mechanisms of pathogen recognition by TLRs
      and cytoplasmic receptors, and then discuss the roles of these receptors in the
      development of adaptive immunity in response to viral infection.

PMID- 21893538
TI  - Progress in the rational design of an AIDS vaccine.
AB  - Human immunodeficiency virus-1 (HIV-1) has a high degree of genetic and antigenic
      diversity that has impeded the development of an effective vaccine using
      traditional methods. We are attempting to develop an AIDS vaccine by employing
      strategies that include structural biology and computational modelling, in an
      effort to develop immunogens capable of eliciting neutralizing antibodies of the
      requisite breadth and potency against circulating strains of HIV-1.

PMID- 21893539
TI  - Towards universal influenza vaccines?
AB  - Vaccination is the most cost-effective way to reduce the considerable disease
      burden of seasonal influenza. Although seasonal influenza vaccines are effective,
      their performance in the elderly and immunocompromised individuals would benefit
      from improvement. Major problems related to the development and production of
      pandemic influenza vaccines are response time and production capacity as well as
      vaccine efficacy and safety. Several improvements can be envisaged. Vaccine
      production technologies based on embryonated chicken eggs may be replaced by cell
      culture techniques. Reverse genetics techniques can speed up the generation of
      seed viruses and new mathematical modelling methods improve vaccine strain
      selection. Better understanding of the correlates of immune-mediated protection
      may lead to new vaccine targets besides the viral haemagglutinin, like the
      neuraminidase and M2 proteins. In addition, the role of cell-mediated immunity
      could be better exploited. New adjuvants have recently been shown to increase the
      breadth and the duration of influenza vaccine-induced protection. Other studies
      have shown that influenza vaccines based on different viral vector systems may
      also induce broad protection. It is to be expected that these developments may
      lead to more universal influenza vaccines that elicit broader and longer
      protection, and can be produced more efficiently.

PMID- 21893541
TI  - Tuberculosis vaccines: beyond bacille Calmette-Guerin.
AB  - Tuberculosis (TB) disease caused by Mycobacterium tuberculosis (M. tb) remains
      one of the leading infectious causes of death and disease throughout the world.
      The only licensed vaccine, Mycobacterium bovis bacille Calmette-Guerin (BCG)
      confers highly variable protection against pulmonary disease. An effective
      vaccination regimen would be the most efficient way to control the epidemic.
      However, BCG does confer consistent and reliable protection against disseminated
      disease in childhood, and most TB vaccine strategies being developed incorporate
      BCG to retain this protection. Cellular immunity is necessary for protection
      against TB and all the new vaccines in development are focused on inducing a
      strong and durable cellular immune response. There are two main strategies being
      pursued in TB vaccine development. The first is to replace BCG with an improved
      whole organism mycobacterial priming vaccine, which is either a recombinant BCG
      or an attenuated strain of M. tb. The second is to develop a subunit boosting
      vaccine, which is designed to be administered after BCG vaccination, and to
      enhance the protective efficacy of BCG. This article reviews the leading
      candidate vaccines in development and considers the current challenges in the
      field with regard to efficacy testing.

PMID- 21893540
TI  - Developing vaccines against foot-and-mouth disease and some other exotic viral
      diseases of livestock.
AB  - Vaccines remain the main tool for the control of livestock viral diseases that
      pose a serious threat to animal and occasionally human health, reduce food
      security, distort trade in animals and their products, and undermine agricultural
      development in poor countries. Globalization and climate change increase the
      likelihood for new patterns of emergence and spread of livestock viruses.
      Conventionally attenuated and killed virus products have had spectacular success,
      and recent examples include the global eradication of rinderpest and the control
      of bluetongue in the UK and northern Europe. However, in many cases, livestock
      vaccines could benefit from improvement in some properties (e.g. stability, speed
      of onset and duration of immunity, and breadth of cross-protection to different
      serotypes or strains) and in some cases are not available at all. Compared with
      human vaccines, uptake of livestock products is highly cost-sensitive and their
      use may also need to be compatible with post-vaccination screening methods to
      determine whether or not animals continue to be infected. Requirements and
      prospects for new or improved vaccines are described for some priority viral
      diseases with potential for transboundary spread, particularly for foot-and-mouth
      disease.

PMID- 21893542
TI  - Contribution of vaccines to our understanding of pneumococcal disease.
AB  - Pneumonia is the leading cause of mortality in children in developing countries
      and is also the leading infectious cause of death in adults. The most important
      cause of pneumonia is the Gram-positive bacterial pathogen, Streptococcus
      pneumoniae, also known as the pneumococcus. It has thus become the leading
      vaccine-preventable cause of death and is a successful and diverse human
      pathogen. The development of conjugate pneumococcal vaccines has made possible
      the prevention of pneumococcal disease in infants, but has also elucidated
      aspects of pneumococcal biology in a number of ways. Use of the vaccine as a
      probe has increased our understanding of the burden of pneumococcal disease in
      children globally. Vaccination has also elucidated the clinical spectrum of
      vaccine-preventable pneumococcal infections; the identification of a biological
      niche for multiple pneumococcal serotypes in carriage and the differential
      invasiveness of pneumococcal serotypes; the impact of pneumococcal transmission
      among children on disease burden in adults; the role of carriage as a precursor
      to pneumonia; the plasticity of a naturally transformable pathogen to respond to
      selective pressure through capsular switching and the accumulation of antibiotic
      resistance determinants; and the role of pneumococcal infections in
      hospitalization and mortality associated with respiratory viral infections,
      including both seasonal and pandemic influenza. Finally, there has been a recent
      demonstration that pneumococcal pneumonia in children may be an important cause
      of hospitalization for those with underlying tuberculosis.

PMID- 21893543
TI  - Evaluation of vaccines against enteric infections: a clinical and public health
      research agenda for developing countries.
AB  - Enteric infections are a major cause of morbidity and mortality in developing
      countries. To date, vaccines have played a limited role in public health efforts
      to control enteric infections. Licensed vaccines exist for cholera and typhoid,
      but these vaccines are used primarily for travellers; and there are two
      internationally licensed vaccines for rotavirus, but they are mainly used in
      affluent countries. The reasons that enteric vaccines are little used in
      developing countries are multiple, and certainly include financial and political
      constraints. Also important is the need for more cogent evidence on the
      performance of enteric vaccines in developing country populations. A partial
      inventory of research questions would include: (i) does the vaccine perform well
      in the most relevant settings? (ii) does the vaccine perform well in all
      epidemiologically relevant age groups? (iii) is there adequate evidence of
      vaccine safety once the vaccines have been deployed in developing countries? (iv)
      how effective is the vaccine when given in conjunction with non-vaccine
      cointerventions? (v) what is the level of vaccine protection against all relevant
      outcomes? and (vi) what is the expected population level of vaccine protection,
      including both direct and herd vaccine protective effects? Provision of evidence
      addressing these questions will help expand the use of enteric vaccines in
      developing countries.

PMID- 21893545
TI  - Therapeutic vaccines for chronic diseases: successes and technical challenges.
AB  - Chronic, non-communicable diseases are the major cause of death and disability
      worldwide and have replaced infectious diseases as the major burden of society in
      large parts of the world. Despite the complexity of chronic diseases, relatively
      few predisposing risk factors have been identified by the World Health
      Organization. Those include smoking, alcohol abuse, obesity, high cholesterol and
      high blood pressure as the cause of many of these chronic conditions. Here, we
      discuss several examples of vaccines that target these risk factors with the aim
      of preventing the associated diseases and some of the challenges they face.

PMID- 21893544
TI  - Vaccines against malaria.
AB  - There is no licenced vaccine against any human parasitic disease and Plasmodium
      falciparum malaria, a major cause of infectious mortality, presents a great
      challenge to vaccine developers. This has led to the assessment of a wide variety
      of approaches to malaria vaccine design and development, assisted by the
      availability of a safe challenge model for small-scale efficacy testing of
      vaccine candidates. Malaria vaccine development has been at the forefront of
      assessing many new vaccine technologies including novel adjuvants, vectored prime
      boost regimes and the concept of community vaccination to block malaria
      transmission. Most current vaccine candidates target a single stage of the
      parasite's life cycle and vaccines against the early pre-erythrocytic stages have
      shown most success. A protein in adjuvant vaccine, working through antibodies
      against sporozoites, and viral vector vaccines targeting the intracellular liver
      stage parasite with cellular immunity show partial efficacy in humans, and the
      anti-sporozoite vaccine is currently in phase III trials. However, a more
      effective malaria vaccine suitable for widespread cost-effective deployment is
      likely to require a multi-component vaccine targeting more than one life cycle
      stage. The most attractive near-term approach to develop such a product is to
      combine existing partially effective pre-erythrocytic vaccine candidates.

PMID- 21893546
TI  - Cancer vaccines.
AB  - While vaccines are primarily thought of in terms of their use for prevention of
      infectious diseases, they can potentially be used to prevent or treat cancer.
      This manuscript explores the rationale for vaccines and immunotherapies for
      cancer from both the scientific and the global needs perspectives. Pathogens that
      are aetiologic agents of certain cancers provide perhaps the most obvious
      successful examples of the prophylactic utility of vaccines (such as the
      hepatitis B vaccine) to prevent not just the infectious disease (hepatitis), but
      the potential subsequent cancer (hepatocellular carcinoma). The use of monoclonal
      antibodies illustrates the effectiveness of the immune system for cancer therapy.
      In addition, the increased understanding of the role and mechanisms of the immune
      system in the processes of immune surveillance, as well as of its failure during
      immunosuppression, have yielded better insights into how to design cancer
      vaccines and immunotherapies. Examples of targets for cancer vaccines will be
      discussed, as will the challenges and few successes in this arena.

PMID- 21893547
TI  - Accelerating introduction of new vaccines: barriers to introduction and lessons
      learned from the recent Haemophilus influenzae type B vaccine experience.
AB  - Adoption of new vaccines in developing countries is critical to reducing child
      mortality and meeting Millennium Development Goal 4. However, such introduction
      has historically suffered from significant delays that can be attributed to
      various factors including (i) lack of recognition of the value of a vaccine, (ii)
      factors related to weak health systems, and (iii) policy considerations.
      Recently, the Global Alliance for Vaccines and Immunization (GAVI) supported
      efforts to accelerate the introduction of Haemophilus influenzae type b (Hib)
      vaccines in developing countries, which resulted in a significant surge in
      vaccine adoption by these countries. The experience with Hib vaccines, as well as
      similar efforts by GAVI to support the introduction of new pneumococcal and
      rotavirus vaccines, provides a strategy for new vaccine adoption that is reviewed
      in this paper, providing a useful model to help accelerate the uptake of other
      life-saving vaccines. This strategy addresses barriers for vaccine adoption by
      focusing on three major areas: (i) communications to increase awareness about the
      various factors needed for evidence-based decisions that meet a country's health
      goals; (ii) research activities to answer key questions that support vaccine
      introduction and long-term programme sustainability; and (iii) coordination with
      the various stakeholders at global, regional and country levels to ensure
      successful programme implementation.

PMID- 21893548
TI  - Vaccines and future global health needs.
AB  - Increased international support for both research into new vaccines and their
      deployment in developing countries has been evident over the past decade. In
      particular, the GAVI Alliance has had a major impact in increasing uptake of the
      six common infant vaccines as well as those against hepatitis B and yellow fever.
      It further aims to introduce pneumococcal and rotavirus vaccines in the near
      future and several others, including those against human papillomavirus,
      meningococcal disease, rubella and typhoid not long after that. In addition,
      there is advanced research into vaccines against malaria, HIV/AIDS and
      tuberculosis. By 2030, we may have about 20 vaccines that need to be used in the
      developing world. Finding the requisite funds to achieve this will pose a major
      problem. A second and urgent question is how to complete the job of global polio
      eradication. The new strategic plan calls for completion by 2013, but both pre
      eradication and post-eradication challenges remain. Vaccines will eventually
      become available beyond the field of infectious diseases. Much interesting work
      is being done in both autoimmunity and cancer. Cutting across disease groupings,
      there are issues in methods of delivery and new adjuvant formulations.

PMID- 21893549
TI  - Accelerating vaccine development and deployment: report of a Royal Society
      satellite meeting.
AB  - The Royal Society convened a meeting on the 17th and 18th November 2010 to review
      the current ways in which vaccines are developed and deployed, and to make
      recommendations as to how each of these processes might be accelerated. The
      meeting brought together academics, industry representatives, research sponsors,
      regulators, government advisors and representatives of international public
      health agencies from a broad geographical background. Discussions were held under
      Chatham House rules. High-throughput screening of new vaccine antigens and
      candidates was seen as a driving force for vaccine discovery. Multi-stakeholder,
      small-scale manufacturing facilities capable of rapid production of clinical
      grade vaccines are currently too few and need to be expanded. In both the human
      and veterinary areas, there is a need for tiered regulatory standards,
      differentially tailored for experimental and commercial vaccines, to allow
      accelerated vaccine efficacy testing. Improved cross-fertilization of knowledge
      between industry and academia, and between human and veterinary vaccine
      developers, could lead to more rapid application of promising approaches and
      technologies to new product development. Identification of best-practices and
      development of checklists for product development plans and implementation
      programmes were seen as low-cost opportunities to shorten the timeline for
      vaccine progression from the laboratory bench to the people who need it.

PMID- 21893550
TI  - Predicting superficial venous incompetence with strain gauge plethysmography.
AB  - BACKGROUND: With currently available effective interventional methods to treat
      superficial venous insufficiency, it becomes particularly important to have a
      simple and reliable method to evaluate the location and severity of venous
      reflux. To date, there are few studies that evaluated plethysmography with and
      without tourniquet application to differentiate superficial from deep venous
      incompetence. OBJECTIVES: To determine if strain gauge plethysmography (SGP) with
      and without tourniquet application can be used to distinguish between the
      superficial and deep venous components of venous incompetence. METHODS: We
      conducted a prospective study using SGP with and without tourniquet application
      and duplex ultrasound (duplex US) to assess the severity and location of venous
      incompetence in 62 patients (85 limbs, 42 women, with an age range of 32-81
      years) referred to our vascular laboratory for haemodynamic evaluation. Based on
      duplex US results, patients were diagnosed with superficial (SVI), deep and
      superficial (mixed) and deep vein incompetence (DVI). RESULTS: Mixed incompetence
      was the most common type. Twenty-three out of 33 limbs in the SVI group
      normalized their refill rate (RR) with tourniquet application (69.6%).
      Normalization of the RR with tourniquet application was less common in the mixed
      (n: 17 out of 40, 42.5%) and DVI (n: 2 out of 6, 33.3%) groups. CONCLUSION: SGP
      with tourniquet application is a simple and fast technique that can identify
      patients with SVI, based on RR improvement, who probably would benefit more from
      ablation procedures. Further studies evaluating impact of SGP with tourniquet
      test results on clinical outcome of SVI invasive treatment are warranted.

PMID- 21893551
TI  - Interface pressure and stiffness in different combinations of compression
      material.
AB  - OBJECTIVES: To compare the interface pressure and stiffness between various
      combinations of compression material. METHODS: Using a stiffness-determining
      device, the interface pressure and stiffness were determined in several
      combinations of five elastic stockings and two elastic bandages. RESULTS: In the
      double stockings system, the interface pressure increased significantly and the
      highest stiffness was observed in double short-stretch stockings. When short
      stretch bandages were applied over either short- or long-stretch stockings, a
      significant increase in stiffness was observed at any initial pressure compared
      with the single use of short-stretch stockings. In double bandage systems, when
      short-stretch bandages were applied over either short- or long-stretch bandages,
      the stiffness increased significantly. When long-stretch bandages were used over
      short-stretch bandages, the stiffness decreased significantly. CONCLUSIONS: The
      stiffness is changeable according to the combinations of material, such as double
      stockings, double bandages and the wearing of bandages over stockings. The use of
      short-stretch bandages as the outside layer produces the highest stiffness at a
      high initial pressure.

PMID- 21893552
TI  - Performance of endovenous foam sclerotherapy in the USA.
AB  - PURPOSE: To assess practice patterns of endovenous foam sclerotherapy (EFS) use
      in the USA. METHODS: A multidisciplinary panel of US experts was convened and
      developed a questionnaire to assess use of EFS. US attendees at the American
      College of Phlebology 2009 Annual Congress were asked to complete the
      questionnaire. RESULTS: Of 776 questionnaires distributed, 239 were completed
      (31%). The majority of respondents (87%) reported using EFS for the treatment of
      venous disorders. Foam sclerotherapy was used by a wide variety of specialists in
      every region of the USA. The most common indication was sclerosis of recurrent
      truncal or tributary veins of the leg. There was variation among practitioners in
      the indications for use, pre- and postprocedural evaluation and procedure
      methodology. CONCLUSIONS: The results of this questionnaire show widespread usage
      of EFS and are important in the development of national quality improvement
      guidelines for the performance of EFS.

PMID- 21893553
TI  - Relationship between platelet indices and spontaneous echo contrast in patients
      with mitral stenosis.
AB  - AIMS: To determine the association of platelet indices with spontaneous echo
      contrast (SEC) in patients with mitral stenosis. METHODS AND RESULTS: A total of
      232 consecutive patients with mitral stenosis who undergoing mitral balloon
      valvuloplasty were enrolled to the study. Patients were divided into two groups
      according to the formation of SEC in the left atrium. Group 1: mitral stenosis
      complicated with SEC; Group 2: mitral stenosis without SEC. Transthoracic
      echocardiography and transoesophageal echocardiography were performed for each
      patient. Complete blood counting parameters were measured and all routine
      biochemical tests were performed. There were 133 patients (mean age 42 +/- 11 and
      74% female) in the SEC(-) group and 99 patients (mean age 45 +/- 10 and 64%
      female) in the SEC(+) group. Plateletcrit (0.25 +/- 0.06 vs. 0.27 +/- 0.07, P =
      0.043) and mean platelet volume (MPV) levels (9.4 +/- 1.1 vs. 10.4 +/- 1.2, P <
      0.001) were significantly higher in the SEC(+) group. When we divided the SEC(+)
      patients into four subgroups according to previously reported criteria, MPV
      levels increased to correlate with the degree of SEC (P < 0.001). At multivariate
      analysis, MPV levels [odds ratio (OR) 2.365, 95% confidence interval (CI) 1.720
      3.251; P < 0.001] and PCT levels (OR 2.699, 95% CI 1.584-4.598; P= 0.033) are
      independent risk factors of SEC in patients with mitral stenosis. CONCLUSION: In
      patients with mitral stenosis, cheaply and easily measurable platelet indices
      including MPV and PCT levels are associated with the presence of SEC and are
      independent risk factors of SEC.

PMID- 21893554
TI  - Development and validation of the cognitive-behavioral therapy skills
      questionnaire.
AB  - Although several theories exist to describe why patients improve in cognitive
      behavioral therapy (CBT), in only a limited number of studies has CBT skill
      acquisition been examined, particularly among patients with complex clinical
      profiles. Thus, the overarching aim of this research was to develop a tool to
      measure patients' use of CBT skills, such that it would have clinical utility for
      patients and therapists during treatment. In Study 1, the authors developed an
      initial set of items for the Cognitive-Behavioral Therapy Skills Questionnaire
      (CBTSQ). They submitted these items to an exploratory factor analysis in an
      initial administration (n = 350) and to a confirmatory factor analysis in a
      second administration (n = 378). Results indicated that there were two factors
      (Behavioral Activation and Cognitive Restructuring) with good factor structure
      and internal consistency, and both the factors evidenced expected relationships
      with other constructs. In Study 2, the criterion validity of the CBTSQ was
      investigated on a patient sample in a CBT-oriented treatment setting. Results
      showed that CBTSQ scores increased following treatment, and Cognitive
      Restructuring and Behavioral Activation scores predicted reduction of overall
      psychiatric symptoms and depression. Thus, the CBTSQ appears to be a promising
      measure of CBT skill acquisition and treatment outcome as well as an instrument
      that can help patients and therapists monitor progress specifically related to a
      CBT skills training treatment approach.

PMID- 21893555
TI  - Mediastinal mass with superior vena cava syndrome.

PMID- 21893556
TI  - Immunohistochemical characterization of calcitonin gene-related peptide in the
      trigeminal system of the familial hemiplegic migraine 1 knock-in mouse.
AB  - INTRODUCTION: Familial hemiplegic migraine type 1 (FHM-1) is caused by mutations
      in the CACNA1A gene, with the R192Q mutation being the most common. Elevated
      calcitonin gene-related peptide (CGRP) levels in acute migraine and clinical
      trials using CGRP receptor antagonists suggest CGRP-related mechanisms are
      important in migraine. METHODS: Wild-type and R192Q knock-in mice were
      anaesthetized and perfused. Using immunohistochemical staining, the expression of
      CGRP in the trigeminocervical complex (TCC) and in the trigeminal and dorsal root
      ganglia was characterized. RESULTS: There was a 38% reduction in the percentage
      of CGRP-immunoreactive cells in the trigeminal ganglia (p < 0.001) of R192Q knock
      in mice compared to wild-type animals. The size distribution profile of CGRP
      immunoreactive cells within the trigeminal ganglia demonstrated no significant
      difference in cell diameter between the two groups (p >= 0.56). CGRP expression
      was also reduced in thoracic ganglia of R192Q knock-in mice (21% vs. 27% in wild
      type group; p < 0.05), but not in other ganglia. In addition, decreased CGRP
      immunoreactivity was observed in the superficial laminae of the TCC in R192Q
      knock-in mice, when compared to the control group (p < 0.005). CONCLUSION: The
      data demonstrates that the FHM-1 CACNA1A mutation alters CGRP expression in the
      trigeminal ganglion and TCC. This suggests further study of these animals is
      warranted to characterize better the role of these mutations in the neurobiology
      of migraine.

PMID- 21893557
TI  - Topiramate in the treatment of migraine: a kainate (glutamate) receptor
      antagonist within the trigeminothalamic pathway.
AB  - BACKGROUND: The development of new agents for the preventive treatment of
      migraine is the greatest unmet need in the therapeutics of primary headaches.
      Topiramate, an anticonvulsant drug, is an effective anti-migraine preventive
      whose mechanism of action is not fully elucidated. Since glutamate plays a major
      role in migraine pathophysiology, the potential action of topiramate through
      glutamatergic mechanisms is of considerable interest. METHODS: Recordings of
      neurons in the trigeminocervical complex (TCC) and the ventroposteromedial
      thalamic nucleus (VPM) of anesthetized rats were made using electrophysiological
      techniques. The effects of intravenous or microiontophorezed topiramate on
      trigeminovascular activation of second- and third-order neurons in the
      trigeminothalamic pathway were characterized. The potential interactions of
      topiramate with the ionotropic glutamate receptors were studied using
      microiontophoresis. RESULTS: Both intravenous and microiontophorized topiramate
      significantly inhibited trigeminovascular activity in the TCC and VPM. In both
      nuclei microiontophoretic application of topiramate significantly attenuated
      kainate receptor-evoked firing but had no effect on N-methyl-d-aspartic acid or
      alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor activation.
      CONCLUSION: The data demonstrate for the first time that topiramate modulates
      trigeminovascular transmission within the trigeminothalamic pathway with the
      kainate receptor being a potential target. Understanding the mechanism of action
      of topiramate may help in the design of new medications for migraine prevention,
      with the data pointing to glutamate-kainate receptors as a fruitful target to
      pursue.

PMID- 21893558
TI  - The effect of amlodipine besylate, losartan potassium, olmesartan medoxomil, and
      other antihypertensives on central aortic blood pressure and biomarkers of
      vascular function.
AB  - Biomarkers are being increasingly used in the study of cardiovascular disease
      because they provide readily quantifiable surrogate endpoints and allow accurate
      assessment of the effects of therapy on particular pathological processes.
      However, in order to be useful, biomarkers must be relevant, predictable,
      accurate, and reproducible. There is compelling evidence from large-scale
      clinical trials that inhibitors of the renin-angiotensin system [angiotensin
      converting enzyme inhibitors and angiotensin type II receptor blockers (ARBs)]
      and calcium channel blockers (CCBs) may have beneficial effects beyond blood
      pressure control in the treatment of hypertension. Biomarkers are expected to
      provide further insight into these beneficial effects and allow for quantitative
      assessment. This review summarizes the published clinical evidence on the effects
      of various antihypertensive drugs, particularly ARBs (e.g. losartan and
      olmesartan medoxomil) and CCBs (e.g. amlodipine), alone and in combination with
      other agents (e.g. hydrochlorothiazide), on central aortic pressure and the
      biomarkers high-sensitivity C-reactive protein (hsCRP), adiponectin, cystatin C,
      homeostasis model assessment of insulin resistance (HOMA-IR), procollagen, tumor
      necrosis factor-alpha, and interleukin-6. Of these biomarkers, the benefits of
      antihypertensive therapy on hsCRP, adiponectin, and HOMA-IR reflect a potential
      for quantifiable long-term vascular benefits.

PMID- 21893559
TI  - The facts behind niacin.
AB  - Although low-density lipoprotein cholesterol (LDL-C) lowering represents the
      mainstay of current lipid treatment, high-density lipoprotein cholesterol (HDL-C)
      has generated increasing interest as a secondary therapeutic target because of
      strong evidence that serum HDL-C concentration is inversely associated with
      coronary heart disease risk. Niacin is a lipid-altering drug that has been used
      to lower cholesterol since the 1950s. In addition to its LDL-C-lowering effects,
      niacin is the most effective agent currently available for raising HDL-C. Despite
      its long history as a lipid-altering drug, only limited data are available
      regarding its clinical benefit alone and in combination with other agents, and
      the majority of studies investigating its impact on clinical outcomes are from
      the pre-statin area. Several studies have demonstrated a beneficial effect of
      treatment with niacin in combination with statin therapy on surrogate
      cardiovascular markers (e.g. carotid intima-media thickness). However, the
      clinical significance of these surrogate markers has been questioned. Two large
      randomized trials will address whether niacin-statin combination therapy is an
      appropriate therapeutic alternative to statin monotherapy.

PMID- 21893560
TI  - Exercise attenuates the premature cardiovascular aging effects of type 2 diabetes
      mellitus.
AB  - Type 2 diabetes mellitus (T2D) is an example of a disease process that results in
      decrements in function additional to those imposed by the inexorable 'primary
      aging' process. These decrements due to disease, rather than primary aging, can
      be termed 'secondary aging', and include the premature development (as early as
      adolescence) of asymptomatic preclinical cardiovascular abnormalities (e.g.
      endothelial dysfunction, arterial stiffness, diastolic dysfunction), as well as
      impaired exercise performance. These abnormalities are important, as they are
      associated with greater cardiovascular morbidity and mortality in people with and
      without T2D. A better understanding of the pathophysiology of secondary
      cardiovascular aging in people with T2D is warranted, and an evaluation of the
      benefits of existing treatments for these abnormalities is useful (e.g. exercise
      training). The focus of this review is to discuss the data relevant to the
      following key postulates: (a) T2D causes premature cardiovascular aging; (b) in
      contrast to primary cardiovascular aging, the premature cardiovascular aging of
      T2D may be modifiable with exercise. The exercise-focused perspective for this
      review is appropriate because impairments in exercise performance are markers of
      premature cardiovascular aging in T2D, and also because exercise training shows
      promise to attenuate some aspects of cardiovascular aging during the preclinical
      stage.

PMID- 21893561
TI  - An analysis of the metabolic syndrome phenotype in systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is associated with an increased risk of
      coronary heart disease (CHD) not fully explained by classic risk factors.
      Metabolic syndrome (MetS) is associated with an increased risk of CHD in the
      general population and whilst its prevalence is increased in SLE, its phenotypic
      expression may differ. We studied 200 women with SLE and 100 controls and
      compared the prevalence of MetS and its individual components. We examined
      whether any SLE features were associated with MetS and whether MetS in SLE
      patients was associated with carotid plaque. Patients with SLE were more likely
      to meet the MetS criteria (age-adjusted OR 2.1 (1.1-3.8)). However, this was not
      due to increased central obesity (median waist circumference 84 cm vs. 82 cm, p =
      0.65) but rather increased prevalence of hypertension (p <0.01) and low HDL
      cholesterol (p = 0.01). In a multivariable analysis, age, disease duration, low
      complement C3 and corticosteroid use ever, were associated with the presence of
      MetS in SLE. Overall MetS was not associated with the presence of carotid plaque
      in either SLE or controls. We have shown that MetS is more prevalent in SLE, but
      the lupus-MetS phenotype reflects risk factor changes driven by disease activity
      and steroid exposure, rather than obesity. Reliance on clinical measures of
      central obesity to consider MetS in SLE is not reliable and continued attention
      to individual CHD risk factors is recommended.

PMID- 21893562
TI  - Significance of glomerular activation of the alternative pathway and lectin
      pathway in lupus nephritis.
AB  - The objective of the present study was to elucidate the association between
      glomerular complement depositions belonging to the alternative (AP) and lectin
      (LP) pathways, and clinical findings of lupus nephritis (LN). Immunofluorescence
      (IF) was performed on 17 LN patients using antibodies against factor B, factor H,
      properdin, mannose-binding lectin (MBL) and L-ficolin. Compared with factor
      B/factor H negative patients (n = 9), positive patients (n = 8) showed longer
      duration of LN (p < 0.05) and more severe interstitial fibrosis (p < 0.05).
      Eleven patients had properdin deposition in glomeruli, and in three of them, with
      a duration of LN of less than 1 month, factor B was undetectable. Compared with
      properdin negative patients (n = 6), positive patients (n = 11) showed
      significantly higher urinary protein excretion (p < 0.01). MBL/L-ficolin positive
      patients (n = 11) also had significantly higher urinary protein excretion (p <
      0.05) compared with negative patients (n = 6). An independent association was
      found between glomerular deposition of properdin and that of MBL/L-ficolin (p <
      0.01) in addition to factor B/factor H. Traces of glomerular activation of AP and
      LP reflected the clinical status of LN. It appears that glomerular deposition of
      each complement component, especially properdin, may be an index of the
      histological activity of LN.

PMID- 21893563
TI  - Mobile phone tracking could help target aid after disasters, study shows.

PMID- 21893564
TI  - FDA is to hold public meeting to discuss reasons for drug shortages.

PMID- 21893565
TI  - Tobacco company makes freedom of information request for university's research.

PMID- 21893566
TI  - Haiti reconstruction is failing to reduce maternal mortality, report warns.

PMID- 21893567
TI  - Manufacturer recalls commonly used painkiller amid fears of possible sabotage.

PMID- 21893568
TI  - Can a multifaceted educational intervention targeting both nurses and physicians
      change the prescribing of antibiotics to nursing home residents? A cluster
      randomized controlled trial.
AB  - OBJECTIVES: To assess the impact of a multifaceted educational intervention
      concerning treatment of infections in the nursing home setting. METHODS: We used
      a cluster randomized controlled trial. Fifty-eight nursing homes in Sweden were
      randomly assigned either to educational intervention or control. The intervention
      consisted of small educational group sessions with nurses and physicians,
      feedback on prescribing, presentation of guidelines and written materials. The
      primary outcome was the proportion of quinolones prescribed for lower urinary
      tract infection (UTI) in women. Secondary outcomes were for all infections:
      number of UTIs per resident, proportion of recorded infections treated with an
      antibiotic, proportion of infections handled by physicians as 'wait and see', and
      for lower UTI in women, proportion of nitrofurantoin. RESULTS: Of the 58 nursing
      homes, 46 completed the study. A total of 702 and 540 infections were recorded
      pre- and post-intervention. The proportion of quinolones decreased significantly
      in the intervention and control groups, by -0.196 (9/93 to 36/123) and -0.224
      (4/66 to 31/109), respectively [95% confidence interval (CI) -0.338, -0.054 and 
      0.394, -0.054], but the difference between intervention and control groups was
      not significant, with an absolute risk reduction of 0.028 (95% CI -0.193, 0.249).
      The changes in proportion of infections treated with antibiotics and proportion
      of infections handled by physicians as 'wait and see' was significant in
      comparison with controls: -0.124 (95% CI -0.228, -0.019) and 0.143 (95% CI 0.047,
      0.240). No intervention effect could be seen for the other outcomes. CONCLUSIONS:
      The educational intervention had no effect on the primary outcome, but decreased
      the overall prescribing of antibiotics.

PMID- 21893569
TI  - Human ZG16p recognizes pathogenic fungi through non-self polyvalent mannose in
      the digestive system.
AB  - Human zymogen granule protein 16 (ZG16p) contains a Jacalin-like lectin domain,
      although its glycan-binding properties are not fully understood. Here, we
      screened the glycan-binding specificity of ZG16p by recently developed
      glycoconjugate microarray. ZG16p appeared to exhibit selective binding to alpha-
      and beta-linked mannose-polyacrylamide-biotin probes. In more quantitative
      analysis using frontal affinity chromatography, dissociation constants to two
      types of polyvalent mannose, i.e. high-density mannose and yeast mannan, were
      determined to be 1.3 and 1.7 uM, respectively. Mutation of the evolutionarily
      conserved amino acid Asp151, which is involved in sugar binding among the Jacalin
      related lectins (JRLs), abolished binding activity to mannose. By
      immunohistochemical staining, ZG16p was specifically detected in mucus-secreting
      cells of the digestive system such as serosanguineous acinar cells of the parotid
      gland, acinar cells of the pancreas and goblet cells of the intestine. Finally,
      we showed that ZG16p recognizes pathogenic Candida and Malassezia species in a
      polyvalent mannose-dependent manner. We propose that ZG16p is a novel member of
      mannose-specific JRLs, which recognizes pathogenic fungi through non-self
      polyvalent mannose in the digestive system.

PMID- 21893571
TI  - Papaya epicarp extract protects against hydrogen peroxide-induced oxidative
      stress in human SH-SY5Y neuronal cells.
AB  - Recent studies indicated that regular consumption of antioxidant-rich foods
      reduces cellular oxidative stress and protects against health-related problems.
      This study aimed to assess the in vitro antioxidant properties of the papaya
      epicarp extract against hydrogen peroxide (H(2)O(2))-induced oxidative stress in
      human SH-SY5Y neuronal cells. Our study revealed that papaya epicarp extract
      acted as a potent free radical scavenger and provided neuroprotection against
      H(2)O(2)-induced oxidative stress. Papaya epicarp extract ameliorated glutathione
      depletion, restored total antioxidant capacity and augmented the inhibition of
      antioxidant enzymes (catalase, glutathione peroxidases and superoxide dismutase).
      In conclusion, papaya epicarp extract can be used as a functional dietary
      ingredient that might help in reducing the neurological health problems
      associated with various oxidative stress insults.

PMID- 21893570
TI  - Phytotherapy in a rat model of hyperoxaluria: the antioxidant effects of
      quercetin involve serum paraoxonase 1 activation.
AB  - Serum paraoxonase 1 (PON1) has been reported to be an important contributor to
      the antioxidant and anti-inflammatory activities of HDL, avoiding LDL oxidation.
      The activity of this enzyme is reduced in patients with renal insufficiency,
      caused by elevated oxidative stress and disturbances of apolipoprotein
      metabolism. Therapeutic utilization of antioxidants to control renal oxidative
      stress may be an effective therapy in renal protection. The aim was to
      investigate the protective effects of several antioxidant compounds against the
      oxidative stress associated to renal failure induced by ethylene glycol (EG),
      focusing on the possible role of serum PON1 activity. Fifty-four male Wistar rats
      were randomly assigned to six groups (n = 9): an untreated control (C) group, an
      EG-treated group, a catechin (CAT)-treated group, an epicatechin (EPI)-treated
      group, a quercetin (QUE)-treated group and a folk herbal extract (FHE)-treated
      group. After 16 d of treatment, calcium oxalate lithiasis was induced in the rats
      using EG. After eight days (treatment + EG), the animals were sacrificed. EG
      treatment impaired kidney composition, increased oxidative damage, and decreased
      serum paraoxonase and arylesterase activities. CAT, QUE and the FHE Fagolitos
      improved oxidative status by enhancing antioxidant defenses - superoxide
      dismutase and PON1 activities - and reducing oxidative damage, thus reinforcing
      the idea of a possible role of PON1 in the protective effects of QUE against the
      deleterious consequences of oxidative stress in kidney.

PMID- 21893572
TI  - Janus kinase/signal transducer and activator of transcription 3 signaling pathway
      is crucial in chemokine production from hepatocytes infected by dengue virus.
AB  - Hepatocytes are one of the important targets in dengue virus (DV) infection.
      Chemokines produced in DV infection play important immunopathogenic roles. We
      previously showed that DV infection can directly activate signal transducer and
      activator of transcription 3 (STAT3) in dendritic cells. In the present study, we
      examined the possible involvement of the Janus kinase (JAK)/STAT3 pathway in
      chemokine production from DV-infected hepatocytes. HepG2 cells were infected by
      DV. The activation of STAT3, nuclear factor-kappaB (NF-kappaB) and other
      transcription factors was determined by Western blotting or electrophoretic
      mobility shift assay. The concentrations of chemokines were measured by enzyme
      linked immunosorbent assay. Virus titers were determined by plaque assays. A
      genetic manipulation with short hairpin RNA (shRNA) was applied to knock-down
      STAT3. Chemotaxis assays were used to evaluate cell migration. We observed that
      DV infection induced phosphorylation of STAT3 and its DNA-binding activity and
      such effects were attenuated by the inhibitor of JAK2 or JAK3. Blocking JAK2 or
      JAK3 reduced DV-induced cell migration and production of chemokines like
      interleukin-8 and regulated upon activation, normal T-cell expressed and secreted
      (RANTES). At high doses, the JAK2 but not JAK3 inhibitor could significantly
      inhibit DV production. Knocking down STAT3 with shRNA suppressed DV-induced
      STAT3, NF-kappaB and AP-1 activation. Furthermore, reduction of STAT3 suppressed
      DV-induced chemokine production and cell migration but had no effect on virus
      production. In conclusion, the results show that the JAK/STAT3 pathway is
      critical in chemokine production from DV-infected hepatocytes. Targeting this
      pathway may be of benefit in the therapy of DV-induced immunopathologies.

PMID- 21893573
TI  - We need to talk about dying.

PMID- 21893574
TI  - Tools and techniques to solve ethical problems.

PMID- 21893575
TI  - Citations for the Human Rights and Nursing Awards 2011.

PMID- 21893576
TI  - Ethical aspects of researching subjective experiences in early-stage dementia.
AB  - This article is based on a qualitative longitudinal study that followed the
      subjective experiences of both people living with dementia and their family
      members during the early stages of the illness. The purpose of this article is to
      describe and reflect on the ethical and methodological issues that occurred
      during data collection. The article focuses on the situation of the person with
      dementia and the family member and the role of the researcher when conducting the
      research interviews. Based on the results of this study, conducting research
      interviews with people with dementia and their family members poses several
      ethical and methodological challenges that must be addressed. In doing so,
      ethically sound dementia-specific research methods will be actively developed
      enhancing our understanding of living with dementia and providing new insights
      into the care of people with dementia and their family members.

PMID- 21893577
TI  - Sustaining citizenship: people with dementia and the phenomenon of social death.
AB  - Social death is apparent when people are considered unworthy of social
      participation and deemed to be dead when they are alive. Some marginalized groups
      are more susceptible to this treatment than others, and one such group is people
      with dementia. Studies into discrimination towards older people are well
      documented and serve as a source of motivation of older people's social movements
      worldwide. Concurrently, theories of ageing and care have been forthcoming in a
      bid to improve the quality of responses to older people in times of need.
      Included in this theorizing has been the analysis of values and approaches that
      paid carers convey to citizens who require their help. In this article, the
      values and approaches of social workers and mental health nurses bring to people
      with dementia are considered within the context of social life and social death.
      It is based on a small study that undertook to critically examine how
      participation of people with dementia was facilitated. A thanatological lens was
      used to interpret inclusive and exclusive practices which potentially create
      opportunity for participation or reinforce the loss of citizenship for older
      people with dementia.

PMID- 21893578
TI  - Dignified death: concept development involving nurses and doctors in pediatric
      intensive care units.
AB  - The aim of this study was to develop the concept of the dignified death of
      children in Brazilian pediatric intensive care units (PICUs). The Hybrid Model
      for Concept Development was used to develop a conceptual structure of dignified
      death in PICUs in an attempt to define the concept. The fieldwork study was
      carried out by means of in-depth interviews with nine nurses and seven physicians
      working in PICUs. Not unexpectedly, the concept of dignified death was found to
      be a complex phenomenon involving aspects related to decisions made by the
      multidisciplinary team as well as those related to care of the child and the
      family. Knowledge of the concept's dimensions can promote reflection on the part
      of healthcare professionals regarding the values and beliefs underlying their
      conduct in end-of-life situations. Our hope is that this study may contribute to
      theoretic and methodological development in the area of end-of-life care.

PMID- 21893579
TI  - Comparison of nurse educators' and nursing students' descriptions of teaching
      codes of ethics.
AB  - This study analysed teaching of nurses' codes of ethics in basic nursing
      education in Finland. A total of 183 educators and 214 students responded to a
      structured questionnaire. The data was analysed by SPSS. Teaching of nurses'
      codes was rather extensive. The nurse-patient relationship was highlighted.
      Educators assessed their teaching statistically significantly more extensive than
      what students' perceptions were. The use of teaching and evaluation methods was
      conventional, but differences between the groups concerning the use of these
      methods were statistically significant. Students' knowledge of and their ability
      to apply the codes was mediocre. Most educators and students assessed educators'
      knowledge of the codes as adequate for teaching. These educators also taught the
      codes more extensively and these students perceived the teaching as more
      extensive. Otherwise educators' and students' socio-demographic variables had
      little association with the teaching. Research should focus on the organization
      and effectiveness of ethics education, and on educators' competence.

PMID- 21893581
TI  - Let the fog be lifted: screening for hepatitis B virus before biological therapy.

PMID- 21893582
TI  - Autoantibodies as biomarkers for the prediction of neuropsychiatric events in
      systemic lupus erythematosus.
AB  - OBJECTIVE: Neuropsychiatric events occur unpredictably in systemic lupus
      erythematosus (SLE) and most biomarker associations remain to be prospectively
      validated. This study examined a disease inception cohort of 1047 SLE patients to
      determine which autoantibodies at enrolment predicted subsequent neuropsychiatric
      events. METHODS: Patients with a recent SLE diagnosis were assessed prospectively
      for up to 10 years for neuropsychiatric events using the American College of
      Rheumatology case definitions. Decision rules of graded stringency determined
      whether neuropsychiatric events were attributable to SLE. Associations between
      the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant
      (LA), anticardiolipin, anti-beta(2) glycoprotein-I, anti-ribosomal P and anti-NR2
      glutamate receptor) were tested by Cox proportional hazards regression. RESULTS:
      Disease duration at enrolment was 5.4 +/- 4.2 months, follow-up was 3.6 +/- 2.6
      years. Patients were 89.1% female with mean (+/-SD) age 35.2 +/- 13.7 years.
      495/1047 (47.3%) developed one or more neuropsychiatric event (total 917 events).
      Neuropsychiatric events attributed to SLE were 15.4% (model A) and 28.2% (model
      B). At enrolment 21.9% of patients had LA, 13.4% anticardiolipin, 15.1% anti
      beta(2) glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. LA
      at baseline was associated with subsequent intracranial thrombosis (total n=22)
      attributed to SLE (model B) (HR 2.54, 95% CI 1.08 to 5.94). Anti-ribosomal P
      antibody was associated with subsequent psychosis (total n=14) attributed to SLE
      (model B) (HR 3.92, 95% CI 1.23 to 12.5, p=0.02). Other autoantibodies did not
      predict neuropsychiatric events. CONCLUSION: In a prospective study of 1047
      recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are
      associated with an increased future risk of intracranial thrombosis and lupus
      psychosis, respectively.

PMID- 21893583
TI  - Long-term safety, efficacy and inhibition of radiographic progression with
      abatacept treatment in patients with rheumatoid arthritis and an inadequate
      response to methotrexate: 3-year results from the AIM trial.
AB  - OBJECTIVE: To evaluate abatacept treatment over 3 years in patients with
      rheumatoid arthritis (RA) refractory to methotrexate (MTX). METHODS: Patients
      randomised to abatacept or placebo (+MTX) during the 1-year double-blind period
      of the Abatacept in Inadequate responders to Methotrexate (AIM) trial received
      open-label abatacept (+MTX) in the long-term extension (LTE). Safety was assessed
      for patients who received >= 1 dose of abatacept, regardless of randomisation
      group. Efficacy was assessed for patients randomised to abatacept who entered the
      LTE. RESULTS: 433 and 219 patients were randomised and treated with abatacept or
      placebo, respectively; 378 and 161 entered the LTE. At year 3, 440/539 patients
      were ongoing. No unexpected safety events were observed in the LTE. By year 3,
      incidence rates of adverse event and serious adverse events were 249.8/100 and
      15.1/100 patient-years, respectively. Incidence rates were generally stable over
      time. At year 3, 84.8%, 63.4% and 37.5% of patients achieved American College of
      Rheumatology (ACR) criteria of 20, 50 and 70, respectively, compared with 82.3%,
      54.3% and 32.4% of patients at year 1. Mean changes in Genant-modified Sharp
      scores were reduced progressively over 3 years, with significantly greater
      inhibition during year 3 compared with year 2 (p=0.022 for total score).
      CONCLUSION: In MTX-inadequate responders with RA, abatacept provided consistent
      safety and sustained efficacy over 3 years. The data suggest an increasing
      inhibitory disease-modifying effect on radiographic progression.

PMID- 21893584
TI  - A case of progressive multifocal leukoencephalopathy in a patient with
      sarcoidosis.

PMID- 21893585
TI  - Identification of novel proteins associated with yeast snR30 small nucleolar RNA.
AB  - H/ACA small nucleolar RNPs (snoRNPs) that guide pseudouridylation reactions are
      comprised of one small nucleolar RNA (snoRNA) and four common proteins (Cbf5,
      Gar1, Nhp2 and Nop10). Unlike other H/ACA snoRNPs, snR30 is essential for the
      early processing reactions that lead to the production of 18S ribosomal RNA in
      the yeast Saccharomyces cerevisiae. To determine whether snR30 RNP contains
      specific proteins that contribute to its unique functional properties, we devised
      an affinity purification strategy using TAP-tagged Gar1 and an RNA aptamer
      inserted in snR30 snoRNA to selectively purify the RNP. Northern blotting and pCp
      labeling experiments showed that S1-tagged snR30 snoRNA can be selectively
      purified with streptavidin beads. Protein analysis revealed that aptamer-tagged
      snR30 RNA was associated with the four H/ACA proteins and a number of additional
      proteins: Nop6, ribosomal proteins S9 and S18 and histones H2B and H4. Using
      antibodies raised against Nop6 we show that endogenous Nop6 localizes to the
      nucleolus and that it cosediments with snR30 snoRNA in sucrose density gradients.
      We demonstrate through primer extension experiments that snR30 snoRNA is required
      for cleavages at site A0, A1 and A2, and that the absence of Nop6 decreases the
      efficiency of cleavage at site A2. Finally, electron microscopy analyses of
      chromatin spreads from cells depleted of snR30 snoRNA show that it is required
      for SSU processome assembly.

PMID- 21893586
TI  - Is the sequence-specific binding of aminoacyl-tRNAs by EF-Tu universal among
      bacteria?
AB  - Three base pairs in the T-stem are primarily responsible for the sequence
      specific interaction of tRNA with Escherichia coli and Thermus thermophilus EF
      Tu. While the amino acids on the surface of EF-Tu that contact aminoacyl-tRNA (aa
      tRNA) are highly conserved among bacteria, the T-stem sequences of individual
      tRNA are variable, making it unclear whether or not this protein-nucleic acid
      interaction is also sequence specific in other bacteria. We propose and validate
      a thermodynamic model that predicts the DeltaG degrees  of any tRNA to EF-Tu
      using the sequence of its three T-stem base pairs. Despite dramatic differences
      in T-stem sequences, the predicted DeltaG degrees  values for the majority of
      tRNA classes are similar in all bacteria and closely match the DeltaG degrees 
      values determined for E. coli tRNAs. Each individual tRNA class has evolved to
      have a characteristic DeltaG degrees  value to EF-Tu, but different T-stem
      sequences are used to achieve this DeltaG degrees  value in different bacteria.
      Thus, the compensatory relationship between the affinity of the tRNA body and the
      affinity of the esterified amino acid is universal among bacteria. Additionally,
      we predict and validate a small number of aa-tRNAs that bind more weakly to EF-Tu
      than expected and thus are candidates for acting as activated amino acid donors
      in processes outside of translation.

PMID- 21893587
TI  - Structural and functional insight into the mechanism of an alkaline exonuclease
      from Laribacter hongkongensis.
AB  - Alkaline exonuclease and single-strand DNA (ssDNA) annealing proteins (SSAPs) are
      key components of DNA recombination and repair systems within many prokaryotes,
      bacteriophages and virus-like genetic elements. The recently sequenced beta
      proteobacterium Laribacter hongkongensis (strain HLHK9) encodes putative homologs
      of alkaline exonuclease (LHK-Exo) and SSAP (LHK-Bet) proteins on its 3.17 Mb
      genome. Here, we report the biophysical, biochemical and structural
      characterization of recombinant LHK-Exo protein. LHK-Exo digests linear double
      stranded DNA molecules from their 5'-termini in a highly processive manner.
      Exonuclease activities are optimum at pH 8.2 and essentially require Mg(2+) or
      Mn(2+) ions. 5'-phosphorylated DNA substrates are preferred over dephosphorylated
      ones. The crystal structure of LHK-Exo was resolved to 1.9 A, revealing a
      'doughnut-shaped' toroidal trimeric arrangement with a central tapered channel,
      analogous to that of lambda-exonuclease (Exo) from bacteriophage-lambda. Active
      sites containing two bound Mg(2+) ions on each of the three monomers were located
      in clefts exposed to this central channel. Crystal structures of LHK-Exo in
      complex with dAMP and ssDNA were determined to elucidate the structural basis for
      substrate recognition and binding. Through structure-guided mutational analysis,
      we discuss the roles played by various active site residues. A conserved two
      metal ion catalytic mechanism is proposed for this class of alkaline
      exonucleases.

PMID- 21893588
TI  - Secondary structure is required for 3' splice site recognition in yeast.
AB  - Higher order RNA structures can mask splicing signals, loop out exons, or
      constitute riboswitches all of which contributes to the complexity of splicing
      regulation. We identified a G to A substitution between branch point (BP) and 3'
      splice site (3'ss) of Saccharomyces cerevisiae COF1 intron, which dramatically
      impaired its splicing. RNA structure prediction and in-line probing showed that
      this mutation disrupted a stem in the BP-3'ss region. Analyses of various COF1
      intron modifications revealed that the secondary structure brought about the
      reduction of BP to 3'ss distance and masked potential 3'ss. We demonstrated the
      same structural requisite for the splicing of UBC13 intron. Moreover, RNAfold
      predicted stable structures for almost all distant BP introns in S. cerevisiae
      and for selected examples in several other Saccharomycotina species. The
      employment of intramolecular structure to localize 3'ss for the second splicing
      step suggests the existence of pre-mRNA structure-based mechanism of 3'ss
      recognition.

PMID- 21893589
TI  - Cation binding to 15-TBA quadruplex DNA is a multiple-pathway cation-dependent
      process.
AB  - A combination of explicit solvent molecular dynamics simulation (30 simulations
      reaching 4 us in total), hybrid quantum mechanics/molecular mechanics approach
      and isothermal titration calorimetry was used to investigate the atomistic
      picture of ion binding to 15-mer thrombin-binding quadruplex DNA (G-DNA) aptamer.
      Binding of ions to G-DNA is complex multiple pathway process, which is strongly
      affected by the type of the cation. The individual ion-binding events are
      substantially modulated by the connecting loops of the aptamer, which play
      several roles. They stabilize the molecule during time periods when the bound
      ions are not present, they modulate the route of the ion into the stem and they
      also stabilize the internal ions by closing the gates through which the ions
      enter the quadruplex. Using our extensive simulations, we for the first time
      observed full spontaneous exchange of internal cation between quadruplex molecule
      and bulk solvent at atomistic resolution. The simulation suggests that expulsion
      of the internally bound ion is correlated with initial binding of the incoming
      ion. The incoming ion then readily replaces the bound ion while minimizing any
      destabilization of the solute molecule during the exchange.

PMID- 21893590
TI  - Interfaces between bacterial and eukaryotic "neuroecology".
AB  - The sensory capacity of bacteria and macroalgae (seaweeds) is limited with
      respect to many modalities (visual, auditory) common in "higher" organisms such
      as animals. Thus, we expect that other modalities, such as chemical signaling and
      sensing, would play particularly important roles in their sensory ecology. Here,
      we discuss two examples of chemical signaling in bacteria and seaweeds: (1) the
      role of chemical defenses and quorum-sensing (QS) regulatory systems in bacterial
      colonization and infection of the red alga Delisea pulchra and their ecological
      consequences, and (2) the regulation of dispersal and differentiation by nitric
      oxide (NO) in bacterial biofilms. Consistent with the goals of neuroecology, in
      both cases, we investigate the links between specific signal-mediated molecular
      mechanisms, and ecological outcomes, for populations or assemblages of bacteria
      or seaweeds. We conclude by suggesting that because of the fundamental role
      played by chemical signaling in bacteria, bacterial systems, either by themselves
      or in interactions with other organisms, have much to offer for understanding
      general issues in neuroecology. Thus, further integration of microbiology with
      the biology of eukaryotes would seem warranted and is likely to prove
      illuminating.

PMID- 21893591
TI  - Morphometric MRI analysis improves detection of focal cortical dysplasia type II.
AB  - Focal cortical dysplasias type II (FCD II) are highly epileptogenic lesions
      frequently causing pharmacoresistant epilepsy. Detection of these lesions on MRI
      is still challenging as FCDs may be very subtle in appearance and might escape
      conventional visual analysis. Morphometric MRI analysis is a voxel-based post
      processing method based on algorithms of the statistical parametric mapping
      software (SPM5). It creates three dimensional feature maps highlighting brain
      areas with blurred grey-white matter junction and abnormal gyration, and thereby
      may help to detect FCD. In this study, we evaluated the potential diagnostic
      value of morphometric analysis as implemented in a morphometric analysis
      programme, compared with conventional visual analysis by an experienced
      neuroradiologist in 91 patients with histologically proven FCD II operated on at
      the University Hospital of Bonn between 2000 and 2010 (FCD IIa, n = 17; IIb, n =
      74). All preoperative MRI scans were evaluated independently (i) based on
      conventional visual analysis by an experienced neuroradiologist and (ii) using
      morphometric analysis. Both evaluators had the same clinical information
      (electroencephalography and semiology), but were blinded to each other's results.
      The detection rate of FCD using morphometric analysis was superior to
      conventional visual analysis in the FCD IIa subgroup (82% versus 65%), while no
      difference was found in the FCD IIb subgroup (92% versus 91%). However, the
      combination of conventional visual analysis and morphometric analysis provided
      complementary information and detected 89 out of all 91 FCDs (98%). The
      combination was significantly superior to conventional visual analysis alone in
      both subgroups resulting in a higher diagnostic sensitivity (94% versus 65%, P =
      0.031 for FCD IIa; 99% versus 91%, P = 0.016 for FCD IIb). In conclusion, the
      additional application of morphometric MRI analysis increases the diagnostic
      sensitivity for FCD II in comparison with conventional visual analysis alone.
      Since detection of FCDs on MRI during the presurgical evaluation markedly
      improves the chance of becoming seizure free postoperatively, we apply
      morphometric analysis in all patients who are MRI-negative after conventional
      visual analysis at our centre.

PMID- 21893592
TI  - Interictal-like network activity and receptor expression in the epileptic human
      lateral amygdala.
AB  - While the amygdala is considered to play a critical role in temporal lobe
      epilepsy, conclusions on underlying pathophysiological mechanisms have been
      derived largely from experimental animal studies. Therefore, the present study
      aimed to characterize synaptic network interactions, focusing on spontaneous
      interictal-like activity, and the expression profile of transmitter receptors in
      the human lateral amygdala in relation to temporal lobe epilepsy.
      Electrophysiological recordings, obtained intra-operatively in vivo in patients
      with medically intractable temporal lobe epilepsy, revealed the existence of
      interictal activity in amygdala and hippocampus. For in vitro analyses, slices
      were prepared from surgically resected specimens, and sections from individual
      specimens were used for electrophysiological recordings, receptor
      autoradiographic analyses and histological visualization of major amygdaloid
      nuclei for verification of recording sites. In the lateral amygdala, interictal
      like activity appeared as spontaneous slow rhythmic field potentials at an
      average frequency of 0.39 Hz, which occurred at different sites with various
      degrees of synchronization in 33.3% of the tested slices. Pharmacological
      blockade of glutamate alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid
      receptors, but not N-methyl-D-aspartate receptors, abolished interictal-like
      activity, while the gamma-aminobutyric acid A-type receptor antagonist
      bicuculline resulted in a dampening of activity, followed by highly synchronous
      patterns of slow rhythmic activity during washout. Receptor autoradiographic
      analysis revealed significantly higher alpha-amino-3-hydroxy-5-methyl-4
      isoxazolepropionic acid, kainate, metabotropic glutamate type 2/3, muscarinic
      type 2 and adrenoceptor alpha(1) densities, whereas muscarinergic type 3 and
      serotonergic type 1A receptor densities were lower in the lateral amygdala from
      epileptic patients in comparison to autopsy controls. Concerning gamma
      aminobutyric acid A-type receptors, agonist binding was unaltered whereas
      antagonist binding sites were downregulated in the epileptic lateral amygdala,
      suggesting an altered high/low-affinity state ratio and concomitant reduced pool
      of total gamma-aminobutyric acid A-type receptors. Together these data indicate
      an abnormal pattern of receptor densities and synaptic function in the lateral
      nucleus of the amygdala in epileptic patients, involving critical alterations in
      glutamate and gamma-aminobutyric acid receptors, which may give rise to domains
      of spontaneous interictal discharges contributing to seizure activity in the
      amygdala.

PMID- 21893593
TI  - Ruth Lehmann: germ cells do things differently. Interview by Caitlin Sedwick.

PMID- 21893594
TI  - New tools for JCB.
AB  - New technologies and approaches in cell biology research necessitate new venues
      for information sharing and publication. JCB continues its support of innovation
      in publishing with the launch of Tools, a new article type for the description of
      methods and high-throughput datasets, and of a new interface for the JCB
      DataViewer for hosting high-content screening datasets in their entirety.

PMID- 21893595
TI  - Bringing Rad52 foci into focus.

PMID- 21893597
TI  - The nucleolus directly regulates p53 export and degradation.
AB  - The correlation between stress-induced nucleolar disruption and abrogation of p53
      degradation is evident after a wide variety of cellular stresses. This link may
      be caused by steps in p53 regulation occurring in nucleoli, as suggested by some
      biochemical evidence. Alternatively, nucleolar disruption also causes
      redistribution of nucleolar proteins, potentially altering their interactions
      with p53 and/or MDM2. This raises the fundamental question of whether the
      nucleolus controls p53 directly, i.e., as a site where p53 regulatory processes
      occur, or indirectly, i.e., by determining the cellular localization of p53/MDM2
      interacting factors. In this work, transport experiments based on heterokaryons,
      photobleaching, and micronucleation demonstrate that p53 regulatory events are
      directly regulated by nucleoli and are dependent on intact nucleolar structure
      and function. Subcellular fractionation and nucleolar isolation revealed a
      distribution of ubiquitylated p53 that supports these findings. In addition, our
      results indicate that p53 is exported by two pathways: one stress sensitive and
      one stress insensitive, the latter being regulated by activities present in the
      nucleolus.

PMID- 21893596
TI  - Cytoskeleton in motion: the dynamics of keratin intermediate filaments in
      epithelia.
AB  - Epithelia are exposed to multiple forms of stress. Keratin intermediate filaments
      are abundant in epithelia and form cytoskeletal networks that contribute to cell
      type-specific functions, such as adhesion, migration, and metabolism. A perpetual
      keratin filament turnover cycle supports these functions. This multistep process
      keeps the cytoskeleton in motion, facilitating rapid and protein biosynthesis
      independent network remodeling while maintaining an intact network. The current
      challenge is to unravel the molecular mechanisms underlying the regulation of the
      keratin cycle in relation to actin and microtubule networks and in the context of
      epithelial tissue function.

PMID- 21893598
TI  - Cdk1 uncouples CtIP-dependent resection and Rad51 filament formation during M
      phase double-strand break repair.
AB  - DNA double-strand break (DSB) resection, which results in RPA-bound single
      stranded DNA (ssDNA), is activated in S phase by Cdk2. RPA-ssDNA activates the
      ATR-dependent checkpoint and homology-directed repair (HDR) via Rad51-dependent
      mechanisms. On the other hand, the fate of DSBs sustained during vertebrate M
      phase is largely unknown. We use cell-free Xenopus laevis egg extracts to examine
      the recruitment of proteins to chromatin after DSB formation. We find that S
      phase extract recapitulates a two-step resection mechanism. M-phase chromosomes
      are also resected in cell-free extracts and cultured human cells. In contrast to
      the events in S phase, M-phase resection is solely dependent on MRN-CtIP. Despite
      generation of RPA-ssDNA, M-phase resection does not lead to ATR activation or
      Rad51 chromatin association. Remarkably, we find that Cdk1 permits resection by
      phosphorylation of CtIP but also prevents Rad51 binding to the resected ends. We
      have thus identified Cdk1 as a critical regulator of DSB repair in M phase. Cdk1
      induces persistent ssDNA-RPA overhangs in M phase, thereby preventing both
      classical NHEJ and Rad51-dependent HDR.

PMID- 21893599
TI  - DLK induces developmental neuronal degeneration via selective regulation of
      proapoptotic JNK activity.
AB  - The c-Jun N-terminal kinase (JNK) signaling pathway is essential for neuronal
      degeneration in multiple contexts but also regulates neuronal homeostasis. It
      remains unclear how neurons are able to dissociate proapoptotic JNK signaling
      from physiological JNK activity. In this paper, we show that the mixed lineage
      kinase dual leucine zipper kinase (DLK) selectively regulates the JNK-based
      stress response pathway to mediate axon degeneration and neuronal apoptosis
      without influencing other aspects of JNK signaling. This specificity is dependent
      on interaction of DLK with the scaffolding protein JIP3 to form a specialized JNK
      signaling complex. Local activation of DLK-based signaling in the axon results in
      phosphorylation of c-Jun and apoptosis after redistribution of JNK to the cell
      body. In contrast, regulation of axon degeneration by DLK is c-Jun independent
      and mediated by distinct JNK substrates. DLK-null mice displayed reduced
      apoptosis in multiple neuronal populations during development, demonstrating that
      prodegenerative DLK signaling is required in vivo.

PMID- 21893600
TI  - Coatomer and dimeric ADP ribosylation factor 1 promote distinct steps in membrane
      scission.
AB  - Formation of coated vesicles requires two striking manipulations of the lipid
      bilayer. First, membrane curvature is induced to drive bud formation. Second, a
      scission reaction at the bud neck releases the vesicle. Using a reconstituted
      system for COPI vesicle formation from purified components, we find that a
      dimerization-deficient Arf1 mutant, which does not display the ability to
      modulate membrane curvature in vitro or to drive formation of coated vesicles, is
      able to recruit coatomer to allow formation of COPI-coated buds but does not
      support scission. Chemical cross-linking of this Arf1 mutant restores vesicle
      release. These experiments show that initial curvature of the bud is defined
      primarily by coatomer, whereas the membrane curvature modulating activity of
      dimeric Arf1 is required for membrane scission.

PMID- 21893602
TI  - Ca(2+) permeable AMPA receptors switch allegiances: mechanisms and consequences.
AB  - The subunit composition of synaptic AMPA receptors can undergo dynamic changes
      during physiological functioning and under pathological conditions. This switch
      in AMPA receptor phenotype involves changes in the level of GluA2 subunits that
      are mediated via regulated AMPA receptor trafficking, modification of local
      protein synthesis and altered gene transcription of GluA2 subunits. Incorporation
      of the GluA2 subunits into an AMPA receptor alters a number of key biophysical
      properties, including Ca(2+) permeability and the waveform of the synaptic
      current. These changes alter the ability of synaptic currents to evoke an action
      potential and therefore have a profound effect on the computational capability of
      individual neurons and thus the output of neuronal circuits.

PMID- 21893601
TI  - Comparative RNAi screening identifies a conserved core metazoan actinome by
      phenotype.
AB  - Although a large number of actin-binding proteins and their regulators have been
      identified through classical approaches, gaps in our knowledge remain. Here, we
      used genome-wide RNA interference as a systematic method to define metazoan actin
      regulators based on visual phenotype. Using comparative screens in cultured
      Drosophila and human cells, we generated phenotypic profiles for annotated actin
      regulators together with proteins bearing predicted actin-binding domains. These
      phenotypic clusters for the known metazoan "actinome" were used to identify
      putative new core actin regulators, together with a number of genes with
      conserved but poorly studied roles in the regulation of the actin cytoskeleton,
      several of which we studied in detail. This work suggests that although our
      search for new components of the core actin machinery is nearing saturation,
      regulation at the level of nuclear actin export, RNA splicing, ubiquitination,
      and other upstream processes remains an important but unexplored frontier of
      actin biology.

PMID- 21893604
TI  - Income differences in stroke mortality: a 12-year follow-up study of the Swedish
      working population.
AB  - AIMS: This study explored the association between income and stroke mortality in
      the total working population in Sweden and examined whether the associations
      differ by gender or for stroke subtypes intracerebral haemorrhage (ICH) or brain
      infarction (BI). METHODS: This was a register-based study among nearly 3 million
      working women and men (30-64 years in 1990) with a 12-year follow up (1991-2002)
      for mortality from stroke (4886 deaths). Income was measured as annual registered
      income from work in 1990. Gender-specific Cox regressions were applied with
      adjustments for sociodemographic covariates. RESULTS: The age-adjusted hazard
      ratio (95% confidence interval) of lowest versus highest income quartile was 1.80
      (1.48-2.19) for any stroke, 1.68 (1.29-2.17) for ICH and 2.23 (1.53-3.22) for BI
      in women, and the corresponding figures for men were 2.12 (1.92-2.34), 2.02 (1.77
      2.31), and 2.09 (1.77-2.46). Adjustment for covariates attenuated these
      associations to 1.69 (1.33-2.15) for any stroke and 1.56 (1.14-2.14) for ICH in
      women and to 1.98 (1.74-2.24) for any stroke and 1.77 (1.44-2.19) for BI in men.
      In contrast, adjustment for covariates amplified the estimates to 2.36 (1.52
      3.66) for BI in women and to 2.05 (1.73-2.44) for ICH in men. CONCLUSIONS: Risk
      of stroke mortality was highest in the lowest income group, with a gradient for
      the intermediate groups, in both women and men. The risk of mortality from BI was
      highest in women with the lowest income and the risk of ICH was highest in men
      with the lowest income.

PMID- 21893603
TI  - SOCS1 is essential for regulatory T cell functions by preventing loss of Foxp3
      expression as well as IFN-{gamma} and IL-17A production.
AB  - Regulatory T cells (T(reg) cells) maintain immune homeostasis by limiting
      inflammatory responses. SOCS1 (suppressor of cytokine signaling 1), a negative
      regulator of cytokine signaling, is necessary for the suppressor functions of
      T(reg) cells in vivo, yet detailed mechanisms remain to be clarified. We found
      that Socs1(-/-) T(reg) cells produced high levels of IFN-gamma and rapidly lost
      Foxp3 when transferred into Rag2(-/-) mice or cultured in vitro, even though the
      CNS2 (conserved noncoding DNA sequence 2) in the Foxp3 enhancer region was fully
      demethylated. Socs1(-/-) T(reg) cells showed hyperactivation of STAT1 and STAT3.
      Because Foxp3 expression was stable and STAT1 activation was at normal levels in
      Ifngamma(-/-)Socs1(-/-) T(reg) cells, the restriction of IFN-gamma-STAT1
      signaling by SOCS1 is suggested to be necessary for stable Foxp3 expression.
      However, Ifngamma(-/-)Socs1(-/-) T(reg) cells had hyperactivated STAT3 and higher
      IL-17A (IL-17) production compared with Ifngamma(-/-)Socs1(+/+) T(reg) cells and
      could not suppress colitis induced by naive T cells in Rag2(-/-) mice. In vitro
      experiments suggested that cytokines produced by Socs1(-/-) T(reg) cells and
      Ifngamma(-/-)Socs1(-/-) T(reg) cells modulated antigen-presenting cells for
      preferential Th1 and Th17 induction, respectively. We propose that SOCS1 plays
      important roles in T(reg) cell integrity and function by maintaining Foxp3
      expression and by suppressing IFN-gamma and IL-17 production driven by STAT1 and
      STAT3, respectively.

PMID- 21893605
TI  - Daily steps among Finnish adults: variation by age, sex, and socioeconomic
      position.
AB  - AIMS: The aim of this study was to provide descriptive population-based pedometer
      data from adults aged 30-45 years in Finland, and to compare daily step counts
      with evidence-based indices. METHODS: The data was collected from 1853
      participants in 7 consecutive days in winter 2007-08 in part of 27-year follow up
      of the Cardiovascular Risk in Young Finns study. RESULTS: The participants took
      (mean+/-standard deviation) 7499 +/- 2908 steps/day. Step counts included 1925 +/
      2052 aerobic steps/day gathered in bouts of at least 10 min continuous
      ambulatory activity. Women had more total steps than men ((7824 +/- 2925 vs. 7089
      +/- 2774; p < 0.001). Although participants had higher mean total steps on
      weekdays than on weekend days, they took more aerobic steps on weekend days than
      weekdays (p < 0.001). High-level non-manual work, and unemployment were
      associated with having fewer total steps, but high-level non-manual workers had
      more aerobic steps than other occupation groups. According to pedometer
      thresholds proposed by Tudor-Locke and Basset, 26% of men and 16% of women could
      be classified as inactive (<5000 steps/day) and 20% of women and 15% of men would
      be classified as active (>10,000 steps/day). CONCLUSIONS: We conclude that about
      one-quarter of men and one-fifth of women are considered as inactive, based on
      the number of daily total steps. Our results suggest that total steps may provide
      a very different picture of activity from aerobic steps; important differences
      are evident by socioeconomic position and day of the week.

PMID- 21893606
TI  - Academic achievement and smoking: is self-efficacy an important factor in
      understanding social inequalities in Finnish adolescents?
AB  - AIMS: Poor academic achievement is strongly related to smoking but studies that
      examine the mechanism between academic achievement and smoking are lacking. The
      aim of this study, therefore, was to examine the smoking-related cognitions (i.e.
      attitude, social influence, self-efficacy and intention to smoke) in relation to
      academic achievement and determine whether these cognitions explain different
      patterns of smoking. METHODS: The study uses the data of a longitudinal study
      that was carried out in Finland, and the sample comprised 1,096 students in
      grades seven to nine. RESULTS: During the seventh-grade students with poor
      academic achievement reported more positive attitudes to smoking and a greater
      social influence of their peers regarding smoking, weaker self-efficacy to refuse
      smoking and more intentions to smoke in the future compared to students with high
      academic achievement. Moreover, the follow-up analyses after a 24-month interval
      revealed that self-efficacy to refuse smoking of students with poor grades had
      become weaker compared to students with high grades. Furthermore, the influence
      of seventh-grade academic achievement predicting ninth-grade weekly smoking was
      partially mediated through the self-efficacy beliefs and the intention to smoke.
      CONCLUSIONS: Differences in academic achievement may have an impact on
      adolescents' self-efficacy beliefs and the intention to smoke in the future. To
      reduce health inequalities a strong input on continuing research to improve
      smoking prevention methods, especially for students with low academic
      achievement, is needed.

PMID- 21893607
TI  - Exposure to secondhand smoke in Finnish workplaces and compliance with national
      smoke-free workplace legislation.
AB  - AIMS: The present study examined time trends and associations in exposure to
      secondhand smoke (SHS) at work in Finland in 1985-2008 and compliance with
      national smoke-free workplace legislation that has been enforced since 1995.
      METHODS: The study population comprised respondents of nationally representative
      annual postal surveys from 1985 to 2008. The differences in the prevalence of SHS
      exposed respondents were measured with particular reference to workplace size and
      workplace smoking arrangements. RESULTS: From 1985 to 2008 daily exposure to SHS
      at work decreased in all workplaces. The annual decrease was largest in 1994-95
      when the smoke-free workplace legislation was enacted. The proportion of exposed
      employees in workplaces with designated smoking rooms was two-fold compared to
      employees in workplaces where no one smoked, and this ratio remained unchanged
      between 1995 and 2008. Employees in small workplaces were exposed most and
      exposure to SHS was lowest in the largest workplaces. CONCLUSIONS: Totally smoke
      free workplaces give better protection against the exposure to SHS than
      workplaces with designated smoking areas. We urge a law reform that does not
      allow any designated smoking rooms indoors. In the prevention of SHS exposure,
      special attention should be directed to small workplaces.

PMID- 21893608
TI  - Health-related risk factors for disability pensions due to musculoskeletal
      diagnoses: a 30-year Finnish twin cohort study.
AB  - AIMS: There is a need to better understand work incapacity due to musculoskeletal
      disorders (MSD) and the factors that contribute to being granted disability
      pension (DP) with such disorders. A twin cohort study would serve a powerful tool
      responding to this knowledge gap by providing information on factors affecting DP
      when controlling for family background. The purpose was to investigate the
      incidence of and risk factors for DP due to any MSD (n=1,819) and specifically
      due to osteoarthritis (OA, n=677) in a twin cohort of 24,043 people over a 30
      year follow-up. METHODS: Data on twin pairs from a mailed questionnaire during
      the baseline year of 1975 were followed up with register data regarding DP,
      emigration, old-age pension, and death. For statistical analysis, univariate and
      multivariate Cox proportional hazard ratios were estimated. RESULTS: Baseline
      musculoskeletal pain, frequency of use of analgesics, body mass index, and
      chronic diseases, as well as education and social class were significant risk
      factors for DP due to MSD at follow-up in both sexes. These factors were also the
      significant predictors of DP due to OA in men. In women, DP due to OA was best
      predicted by baseline musculoskeletal pain and lower social class. CONCLUSIONS:
      The risk of DP due to MSD and OA seemed to be influenced by comorbidities,
      educational level and social class. Analyses of twin pairs discordant for DP
      confirmed the results. Accumulated health problems and chronic conditions during
      the life course may lead to permanent work incapacity.

PMID- 21893609
TI  - Effect of different levels of short-term feed intake on folliculogenesis and
      follicular fluid and plasma concentrations of lactate dehydrogenase, glucose, and
      hormones in Hu sheep during the luteal phase.
AB  - This study investigated the effects of short-term food restriction or
      supplementation on folliculogenesis and plasma and intrafollicular metabolite and
      hormone concentrations. Ewes were randomly assigned to three groups: the control
      group received a maintenance diet (M) while the supplemented group and restricted
      group received 1.5*M and 0.5*M respectively on days 6-12 of their estrous cycle.
      Estrus was synchronized by intravaginal progestogen sponges for 12 days. On days
      7-12, blood samples were taken. After slaughter, the ovarian follicles were
      classified and the follicular fluid was collected. Compared with restriction,
      supplementation shortened the estrous cycle length, decreased the number of
      follicles 2.5-3.5 mm and follicular fluid estradiol (E2) concentration, increased
      the number of follicles>3.5 mm and plasma glucose, insulin and glucagon
      concentrations, and augmented the volume of follicles>2.5 mm. Restricted ewes had
      higher intrafollicular insulin concentration, but it was similar to that of
      supplemented ewes. Compared with follicles<=2.5 mm, the intrafollicular glucose
      and E2 concentrations were increased and the testosterone, insulin, and glucagon
      concentrations and lactate dehydrogenase (LDH) activity were decreased in
      follicles>2.5 mm. Only in restricted ewes were intrafollicular LDH and
      testosterone concentrations in follicles<=2.5 mm not different from those in
      follicles<=2.5 mm. In conclusion, the mechanism by which short-term dietary
      restriction inhibits folliculogenesis may involve responses to intrafollicular
      increased E2, testosterone, and LDH levels in late-stage follicles. This may not
      be due to the variation of intrafollicular insulin level but rather due to
      decreased circulating levels of glucose, insulin, and glucagon.

PMID- 21893611
TI  - The role of an open-space CCTV system in limiting alcohol-related assault
      injuries in a late-night entertainment precinct in a tropical Queensland city,
      Australia.
AB  - Closed circuit television (CCTV) systems which incorporate real-time
      communication links between camera room operators and on-the-ground security may
      limit injuries resulting from alcohol-related assault. This pilot study examined
      CCTV footage and operator records of security responses for two periods totalling
      22 days in 2010-2011 when 30 alcohol-related assaults were recorded.
      Semistructured discussions were conducted with camera room operators during 18 h
      of observation. Camera operators were proactive, efficiently directing street
      security to assault incidents. The system intervened in 40% (n=12) of alcohol
      related assaults, limiting possible injury. This included three incidents judged
      as potentially preventable. A further five (17%) assault incidents were also
      judged as potentially preventable, while 43% (n=13) happened too quickly for
      intervention. Case studies describe security intervention in each category.
      Further research is recommended, particularly to evaluate the effects on
      preventing injuries through targeted awareness training to improve responsiveness
      and enhance the preventative capacity of similar CCTV systems.

PMID- 21893610
TI  - Hedgehog signalling promotes germ cell survival in the rat testis.
AB  - Hedgehog (Hh) signalling has a crucial role in testis development. Sertoli cell
      derived desert hedgehog (DHH) guides the formation of testis cords and
      differentiation of foetal-type Leydig cells. Dhh mutant mice are infertile due to
      a block in germ cell differentiation, hypogonadism and hypoandrogenism. Hh
      signalling pathway components are also expressed in postnatal testis. In the rat
      testis the transcription factor of the Hh pathway, glioma-associated oncogene
      homologue (GLI1), is expressed by a wide variety of germ cells. This suggests
      that Hh signalling is involved in spermatogenesis at many different levels. Our
      data show that canonical Hh signalling is turned off in early condensing
      spermatids that strongly express the negative regulator of the pathway,
      suppressor of fused (SUFU). Most of the Hh pathway specific mRNAs display the
      highest values in stages II-VI of the rat seminiferous epithelial cycle. The key
      endocrine regulator of germ cell differentiation, FSH, down-regulates Dhh mRNA
      levels in vitro. Hh signalling inhibition in vitro leads to massive apoptosis of
      germ cells. In prepubertal rat testis imatinib mesylate-induced inhibition of
      tyrosine kinases impinges on Dhh transcript levels and Hh signalling. Our data
      indicate that Hh signalling is part of the paracrine signalling network in the
      rat testis. It promotes the survival of germ cells and is suppressed by FSH.

PMID- 21893612
TI  - Safety incidents in family medicine.
AB  - OBJECTIVE: To discuss the characteristics of incidents reported to the Medical
      Safety in Community Practice (MSCP) safety learning system. METHODS: Members of
      family physician offices in the Alberta Health Services--Calgary zone,
      confidentially reported patient safety incidents via web or fax from September
      2007 to August 2010. The incident reporting form contained both open-ended and
      closed questions. Incidents were reviewed for their characteristics. RESULTS: A
      total of 19 family practices participated in MSCP. A total of 264 useable reports
      were collected. Reporting was higher when practices first joined and then
      decreased. There was an average of 1.4 reports per month. Physicians submitted
      the majority of reports. Physicians and nurses were more likely to report an
      incident than office staff. The vast majority of reported incidents were judged
      to have 'virtually certain evidence of preventability' (93%). Harm was associated
      with 50% of incidents. Only 1% of the incidents had a severe impact. The top four
      types of incidents reported were documentation (41.4%), medication (29.7%),
      clinical administration (18.7%) and clinical process (17.5%). CONCLUSION: MSCP
      has developed and implemented the first safety learning system in Canada for
      family practice. All clinic members were encouraged to submit reports, but most
      of the incidents were reported by physicians. The vast majority of incidents
      reported were preventable with limited severity. The most frequently reported
      types of incidents fell into the categories of documentation and medication. The
      low reporting rates suggest that for family practices incident reporting may not
      be the most effective method to determine the types and frequency of incidents in
      family medicine.

PMID- 21893613
TI  - Transfusion-associated babesiosis in the United States: a description of cases.
AB  - BACKGROUND: Babesiosis is a potentially life-threatening disease caused by
      intraerythrocytic parasites, which usually are tickborne but also are
      transmissible by transfusion. Tickborne transmission of Babesia microti mainly
      occurs in 7 states in the Northeast and the upper Midwest of the United States.
      No Babesia test for screening blood donors has been licensed. OBJECTIVE: To
      ascertain and summarize data on U.S. transfusion-associated Babesia cases
      identified since the first described case in 1979. DESIGN: Case series. SETTING:
      United States. PATIENTS: Case patients were transfused during 1979-2009 and had
      posttransfusion Babesia infection diagnosed by 2010, without reported evidence
      that another transmission route was more likely than transfusion. Implicated
      donors had laboratory evidence of infection. Potential cases were excluded if all
      pertinent donors tested negative. MEASUREMENTS: Distributions of ascertained
      cases according to Babesia species and period and state of transfusion. RESULTS:
      159 transfusion-associated B. microti cases were included; donors were implicated
      for 136 (86%). The case patients' median age was 65 years (range, <1 to 94
      years). Most cases were associated with red blood cell components; 4 were linked
      to whole blood-derived platelets. Cases occurred in all 4 seasons and in 22 (of
      31) years, but 77% (122 cases) occurred during 2000-2009. Cases occurred in 19
      states, but 87% (138 cases) were in the 7 main B. microti-endemic states. In
      addition, 3 B. duncani cases were documented in western states. LIMITATION: The
      extent to which cases were not diagnosed, investigated, reported, or ascertained
      is unknown. CONCLUSION: Donor-screening strategies that mitigate the risk for
      transfusion transmission are needed. Babesiosis should be included in the
      differential diagnosis of unexplained posttransfusion hemolytic anemia or fever,
      regardless of the season or U.S. region. PRIMARY FUNDING SOURCE: None.

PMID- 21893614
TI  - Screening for lung cancer: it works, but does it really work?
AB  - After the publication of the NLST (National Lung Screening Trial) results,
      physicians will be faced with whether to begin ordering low-dose computed
      tomography (LDCT) of the chest to screen for lung cancer in patients with a
      history of tobacco use. Despite the encouraging reduction in deaths observed by
      using LDCT in the NLST study population, recommending adoption of lung cancer
      screening in general practice is premature. Lessons learned from prostate and
      breast cancer screening should remind us that the reductions in deaths expected
      with screening are unfortunately not as readily achievable as initially believed.
      Furthermore, the potential harms of false-positive findings on chest computed
      tomography are very real. The morbidity and even mortality associated with
      invasive diagnostic testing and surgical resection due to false- and true
      positive findings on computed tomography are likely to increase when the approach
      taken in the NLST is applied in non-specialty care settings and among the
      population at highest risk, namely, those with smoking-related comorbid
      conditions. Although the NLST results are perhaps encouraging, they do not tell
      us enough that we can be sure that patients who undergo LDCT in an attempt to
      find early-stage lung cancer will have more benefit than harm.

PMID- 21893615
TI  - Screening for lung cancer: for patients at increased risk for lung cancer, it
      works.
AB  - Screening for lung cancer is not currently recommended, even in persons at high
      risk for this condition. Most patients with lung cancer present with symptomatic
      disease that is usually at an incurable, advanced stage. The recently reported
      NLST (National Lung Screening Trial) showed a 20% decrease in deaths from lung
      cancer in high-risk persons undergoing screening with low-dose computed
      tomography of the chest compared with chest radiography. The high-risk group
      included in the trial comprised asymptomatic persons aged 55 to 74 years, with
      smoking history of at least 30 pack-years. Screening with low-dose computed
      tomography detected more cases of early-stage lung cancer and fewer cases of
      advanced-stage cancer, confirming that screening has shifted the stage of cancer
      at diagnosis and provides more persons with the opportunity for curative
      treatment. Although computed tomography screening has risks and limitations, the
      20% decrease in deaths is the single most dramatic decrease ever reported for
      deaths from lung cancer, with the possible exception of smoking cessation.
      Physicians should offer computed tomography screening for lung cancer to patients
      who fit the high-risk profile defined in the NLST.

PMID- 21893616
TI  - Transfusion-associated babesiosis: shouldn't we be ticked off?

PMID- 21893617
TI  - Summaries for patients. Outcomes after gastric bypass and duodenal switch
      surgery.

PMID- 21893618
TI  - Summaries for patients. Improving each additional lifestyle factor further
      reduces the risk for diabetes.

PMID- 21893619
TI  - Summaries for patients. Does cognitive impairment increase the risk for death in
      older adults?

PMID- 21893620
TI  - In the clinic. Sickle cell disease.
AB  - This issue provides a clinical overview of sickle cell disease 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- 21893621
TI  - Weight loss, cardiovascular risk factors, and quality of life after gastric
      bypass and duodenal switch: a randomized trial.
AB  - BACKGROUND: Gastric bypass and duodenal switch are currently performed bariatric
      surgical procedures. Uncontrolled studies suggest that duodenal switch induces
      greater weight loss than gastric bypass. OBJECTIVE: To determine whether duodenal
      switch leads to greater weight loss and more favorable improvements in
      cardiovascular risk factors and quality of life than gastric bypass. DESIGN:
      Randomized, parallel-group trial. (ClinicalTrials.gov registration number:
      NCT00327912) SETTING: 2 academic medical centers (1 in Norway and 1 in Sweden).
      PATIENTS: 60 participants with a body mass index (BMI) between 50 and 60 kg/m(2).
      INTERVENTION: Gastric bypass (n = 31) or duodenal switch (n = 29). MEASUREMENTS:
      The primary outcome was the change in BMI after 2 years. Secondary outcomes
      included anthropometric measures; concentrations of blood lipids, glucose,
      insulin, C-reactive protein, and vitamins; and health-related quality of life and
      adverse events. RESULTS: Fifty-eight of 60 participants (97%) completed the
      study. The mean reductions in BMI were 17.3 kg/m(2) (95% CI, 15.7 to 19.0
      kg/m(2)) after gastric bypass and 24.8 kg/m(2) (CI, 23.0 to 26.5 kg/m(2)) after
      duodenal switch (mean between-group difference, 7.44 kg/m(2) [CI, 5.24 to 9.64
      kg/m(2)]; P < 0.001). Total cholesterol concentration decreased by 0.24 mmol/L
      (CI, -0.03 to 0.50 mmol/L) (9.27 mg/dL [CI, -1.16 to 19.3 mg/dL]) after gastric
      bypass and 1.07 mmol/L (CI, 0.79 to 1.35 mmol/L) (41.3 mg/dL [CI, 30.5 to 52.1
      mg/dL]) after duodenal switch (mean between-group difference, 0.83 mmol/L [CI,
      0.48 to 1.18 mmol/L]; 32.0 mg/dL [CI, 18.5 to 45.6 mg/dL]; P <= 0.001).
      Reductions in low-density lipoprotein cholesterol concentration, anthropometric
      measures, fat mass, and fat-free mass were also greater after duodenal switch (P
      <= 0.010 for each between-group comparison). Both groups had reductions in blood
      pressure and mean concentrations of glucose, insulin, and C-reactive protein,
      with no between-group differences. The duodenal switch group, but not the gastric
      bypass group, had reductions in concentrations of vitamin A and 25-hydroxyvitamin
      D. Most Short Form-36 Health Survey dimensional scores improved in both groups,
      with greater improvement in 1 of 8 domains (bodily pain) after gastric bypass.
      From surgery until 2 years, 10 participants (32%) had adverse events after
      gastric bypass and 18 (62%) after duodenal switch (P = 0.021). Adverse events
      related to malnutrition occurred only after duodenal switch. LIMITATION: Clinical
      experience was greater with gastric bypass than with duodenal switch at the study
      centers. CONCLUSION: Duodenal switch surgery was associated with greater weight
      loss, greater reductions of total and low-density lipoprotein cholesterol
      concentrations, and more adverse events. Improvements in other cardiovascular
      risk factors and quality of life were similar after both procedures. PRIMARY
      FUNDING SOURCE: South-Eastern Norway Regional Health Authority.

PMID- 21893623
TI  - Cognitive impairment: an independent predictor of excess mortality: a cohort
      study.
AB  - BACKGROUND: Dementia is a leading cause of death among older adults, but less is
      known about the mortality risk associated with milder forms of cognitive
      impairment. OBJECTIVE: To determine whether cognitive impairment is independently
      associated with increased long-term mortality in primary care patients aged 60
      years and older. DESIGN: Linkage of electronic health records from a cohort
      recruited between January 1991 and May 1993 with data from the National Death
      Index through 31 December 2006. SETTING: A public safety-net hospital and its
      community health centers. PATIENTS: 3957 older adults aged 60 to 102 years who
      were screened at scheduled primary care appointments. MEASUREMENTS: At baseline,
      patients were screened for cognitive impairment by using the Short Portable
      Mental Status Questionnaire and were categorized into groups with no, mild, or
      moderate to severe cognitive impairment. Baseline data from comprehensive
      electronic health records were linked with vital status obtained from the
      National Death Index. Kaplan-Meier survival curves compared time to death for the
      groups with cognitive impairment. Cox proportional hazards models controlled for
      mortality risk factors. RESULTS: At baseline, 3157 patients had no cognitive
      impairment, 533 had mild impairment, and 267 had moderate to severe impairment.
      Overall, 2385 of the 3957 patients (60.3%) died during the observation period:
      1812 (57.4%) patients with no cognitive impairment, 363 (68.1%) patients with
      mild impairment, and 210 (78.7%) patients with moderate to severe impairment.
      Both mild and moderate to severe cognitive impairment were associated with
      increased mortality hazard independent of other mortality risk factors (hazard
      ratio, 1.184 [95% CI, 1.051 to 1.334] and for mild impairment 1.447 [CI, 1.235 to
      1.695] for moderate to severe impairment). Median survival for all 3957
      participants was 129 months. Median survival for participants with no, mild, and
      moderate to severe cognitive impairment was 138, 106, and 63 months,
      respectively. LIMITATIONS: Cognition was assessed only at enrollment by using a
      screening instrument. Participants were drawn from a single safety-net health
      system and had low educational and socioeconomic status, which limits
      generalizability to other populations. Changes in cognition, function, and
      comorbid conditions were not measured over time. CONCLUSION: Both mild and
      moderate to severe cognitive impairment as identified by the Short Portable
      Mental Status Questionnaire are associated with an increased risk for mortality.
      PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

PMID- 21893622
TI  - Lifestyle factors and risk for new-onset diabetes: a population-based cohort
      study.
AB  - BACKGROUND: Epidemiologic data on the combined influence of several lifestyle
      factors on diabetes risk are rare, particularly among older adults. OBJECTIVE: To
      examine how combinations of lifestyle risk factors relate to the 11-year risk for
      incident diabetes. DESIGN: Population-based prospective cohort study. SETTING:
      National Institutes of Health (NIH)-AARP Diet and Health Study. PARTICIPANTS:
      114,996 men and 92,483 women, aged 50 to 71 years in 1995 to 1996, without
      evidence of heart disease, cancer, or diabetes. MEASUREMENTS: A comprehensive
      survey of demographic characteristics and lifestyle factors, including dietary
      intake, body weight and height, physical activity, smoking, and alcohol
      consumption at baseline (1995 to 1996). Low-risk groups were formed by
      dichotomizing each lifestyle factor. Incident self-reported, physician-diagnosed
      diabetes was identified with a follow-up survey in 2004 to 2006. RESULTS: 11,031
      men (9.6%) and 6969 women (7.5%) developed new-onset diabetes. For each
      additional lifestyle factor in the low-risk group, the odds for diabetes were 31%
      lower (odds ratio [OR], 0.69 [95% CI, 0.68 to 0.71]) among men and 39% lower (OR,
      0.61 [CI, 0.60 to 0.63]) among women. Men and women whose diet score, physical
      activity level, smoking status, and alcohol use were all in the low-risk group
      had ORs for diabetes of 0.61 (CI, 0.56 to 0.66) and 0.43 (CI, 0.34 to 0.55),
      respectively. When absence of overweight or obesity was added, the respective ORs
      were 0.28 (CI, 0.23 to 0.34) and 0.16 (CI, 0.10 to 0.24) for men and women.
      Results did not differ by family history of diabetes or level of adiposity.
      LIMITATION: The study was observational, with potential for residual confounding.
      CONCLUSION: Lifestyle factors, when considered in combination, are associated
      with a substantial reduction in risk for diabetes. PRIMARY FUNDING SOURCE: The
      NIH-AARP Diet and Health Study was supported by the Intramural Research Program
      of the NIH.

PMID- 21893625
TI  - Maintaining connections: some thoughts on the value of intensive care unit
      rounding for general medicine ward teams.
AB  - When established ward patients are unexpectedly transferred to an intensive care
      unit (ICU), the ward team should continue to follow them. Although there may be
      reasons not to do so, the advantages outweigh the obstacles. Great pedagogic
      value can be gained from following patients after acute decompensation, but a
      more important reason is that by following patients into the ICU, the ward team
      can enact for both patients and their families the twin virtues of caring and
      continuity. Doing so also demonstrates the highest ideals of medicine-that we are
      focused not on defined areas of turf, but on our patient's well-being. It shows
      that we are not merely doing narrowly defined "shift work," but that we truly
      care about our patients. Rounding on established patients who have been
      transferred into the ICU is the sort of behavior that undergirds the fundamental
      bases of professionalism. It takes a few minutes from a busy day, but it can be
      incredibly beneficial for families, patients, and the ideals of medicine.

PMID- 21893624
TI  - Analysis of informed consent document utilization in a minimal-risk genetic
      study.
AB  - BACKGROUND: The signed informed consent document certifies that the process of
      informed consent has taken place and provides research participants with
      comprehensive information about their role in the study. Despite efforts to
      optimize the informed consent document, only limited data are available about the
      actual use of consent documents by participants in biomedical research.
      OBJECTIVE: To examine the use of online consent documents in a minimal-risk
      genetic study. DESIGN: Prospective sibling cohort enrolled as part of a genetic
      study of hematologic and common human traits. SETTING: University of Michigan
      Campus, Ann Arbor, Michigan. PARTICIPANTS: Volunteer sample of healthy persons
      with 1 or more eligible siblings aged 14 to 35 years. Enrollment was through
      targeted e-mail to student lists. A total of 1209 persons completed the study.
      MEASUREMENTS: Time taken by participants to review a 2833-word online consent
      document before indicating consent and identification of a masked hyperlink near
      the end of the document. RESULTS: The minimum predicted reading time was 566
      seconds. The median time to consent was 53 seconds. A total of 23% of
      participants consented within 10 seconds, and 93% of participants consented in
      less than the minimum predicted reading time. A total of 2.5% of participants
      identified the masked hyperlink. LIMITATION: The online consent process was not
      observed directly by study investigators, and some participants may have viewed
      the consent document more than once. CONCLUSION: Few research participants
      thoroughly read the consent document before agreeing to participate in this
      genetic study. These data suggest that current informed consent documents,
      particularly for low-risk studies, may no longer serve the intended purpose of
      protecting human participants, and the role of these documents should be
      reassessed. PRIMARY FUNDING SOURCE: National Institutes of Health.

PMID- 21893626
TI  - Long-term opioid therapy reconsidered.
AB  - In the past 20 years, primary care physicians have greatly increased prescribing
      of long-term opioid therapy. However, the rise in opioid prescribing has outpaced
      the evidence regarding this practice. Increased opioid availability has been
      accompanied by an epidemic of opioid abuse and overdose. The rate of opioid
      addiction among patients receiving long-term opioid therapy remains unclear, but
      research suggests that opioid misuse is not rare. Recent studies report increased
      risks for serious adverse events, including fractures, cardiovascular events, and
      bowel obstruction, although further research on medical risks is needed. New data
      indicate that opioid-related risks may increase with dose. From a societal
      perspective, higher-dose regimens account for the majority of opioids dispensed,
      so cautious dosing may reduce both diversion potential and patient risks for
      adverse effects. Limiting long-term opioid therapy to patients for whom it
      provides decisive benefits could also reduce risks. Given the warning signs and
      knowledge gaps, greater caution and selectivity are needed in prescribing long
      term opioid therapy. Until stronger evidence becomes available, clinicians should
      err on the side of caution when considering this treatment.

PMID- 21893627
TI  - Primum non nocere.

PMID- 21893628
TI  - A lot to ask.

PMID- 21893629
TI  - No question of denial.

PMID- 21893630
TI  - The systemic capillary leak syndrome.

PMID- 21893631
TI  - Effect of patient self-testing and self-management of long-term anticoagulation
      on major clinical outcomes.

PMID- 21893632
TI  - Off-label use of recombinant factor VIIa.

PMID- 21893633
TI  - Off-label use of recombinant factor VIIa.

PMID- 21893634
TI  - A hemorrhage of off-label use.

PMID- 21893635
TI  - Individualizing glycemic targets in type 2 diabetes mellitus.

PMID- 21893636
TI  - Targeting interleukin-5 in refractory and relapsing Churg-Strauss syndrome.

PMID- 21893637
TI  - Prevalence of polypharmacy exposure among hospitalized children in the United
      States.
AB  - OBJECTIVE: To assess the prevalence and patterns of exposure to drugs and
      therapeutic agents among hospitalized pediatric patients. DESIGN: Retrospective
      cohort study. SETTING: A total of 411 general hospitals and 52 children's
      hospitals throughout the United States. PATIENTS: A total of 587 427 patients
      younger than 18 years, excluding healthy newborns, hospitalized in 2006,
      representing one-fifth of all pediatric admissions in the United States. MAIN
      OUTCOME MEASURES: Daily and cumulative exposure to drugs and therapeutic agents.
      RESULTS: The most common exposures varied by patient age and by hospital type,
      with acetaminophen, albuterol, various antibiotics, fentanyl, heparin, ibuprofen,
      morphine, ondansetron, propofol, and ranitidine being among the most prevalent
      exposures. A considerable fraction of patients were exposed to numerous
      medications: in children's hospitals, on the first day of hospitalization,
      patients younger than 1 year at the 90th percentile of daily exposure to distinct
      medications received 11 drugs, and patients 1 year or older received 13 drugs; in
      general hospitals, 8 and 12 drugs, respectively. By hospital day 7, in children's
      hospitals, patients younger than 1 year at the 90th percentile of cumulative
      exposure to distinct distinct medications had received 29 drugs, and patients 1
      year or older had received 35; in general hospitals, 22 and 28 drugs,
      respectively. Patients with less common conditions were more likely to be exposed
      to more drugs (P = .001). CONCLUSION: A large fraction of hospitalized pediatric
      patients are exposed to substantial polypharmacy, especially patients with rare
      conditions.

PMID- 21893639
TI  - Pediatric polypharmacy: time to lock the medicine cabinet?

PMID- 21893640
TI  - Parental smoking and the risk of middle ear disease in children: a systematic
      review and meta-analysis.
AB  - OBJECTIVE: A systematic review and meta-analysis of studies of the association
      between secondhand tobacco smoke (SHTS) and middle ear disease (MED) in children.
      DATA SOURCES: MEDLINE, EMBASE, and CAB abstracts (through December 2010) and
      reference lists. STUDY SELECTION: Sixty-one epidemiological studies of children
      assessing the effect of SHTS on outcomes of MED. Articles were reviewed, and the
      data were extracted and synthesized by 2 researchers. MAIN OUTCOME EXPOSURES:
      Children's SHTS exposure. MAIN OUTCOME MEASURES: Middle ear disease in children.
      RESULTS: Living with a smoker was associated with an increased risk of MED in
      children by an odds ratio (OR) of 1.62 (95% CI, 1.33-1.97) for maternal postnatal
      smoking and by 1.37 (95% CI, 1.25-1.50) for any household member smoking.
      Prenatal maternal smoking (OR, 1.11; 95% CI, 0.93-1.31) and paternal smoking (OR,
      1.24; 95% CI, 0.98-1.57) were associated with a nonsignificant increase in the
      risk of MED. The strongest effect was on the risk of surgery for MED, where
      maternal postnatal smoking increased the risk by an OR of 1.86 (95% CI, 1.31
      2.63) and paternal smoking by 1.83 (95% CI, 1.61-2.07). CONCLUSIONS: Exposure to
      SHTS, particularly to smoking by the mother, significantly increases the risk of
      MED in childhood; this risk is particularly strong for MED requiring surgery. We
      have shown that per year 130 200 of child MED episodes in the United Kingdom and
      292 950 of child frequent ear infections in the United States are directly
      attributable to SHTS exposure in the home.

PMID- 21893641
TI  - Acute and posttraumatic stress symptoms in a prospective gene x environment study
      of a university campus shooting.
AB  - CONTEXT: The serotonin transporter (SLC6A4) has been associated with several
      stress-related syndromes including posttraumatic stress disorder (PTSD). The
      ability to detect meaningful associations is largely dependent on reliable
      measures of preexisting trauma. OBJECTIVE: To study the association of genetic
      variants within SLC6A4 with acute and posttraumatic stress symptoms in a civilian
      cohort with known levels of preexisting trauma and PTSD symptoms collected prior
      to a shared index traumatic event. DESIGN: Ongoing longitudinal study. SETTING:
      On February 14, 2008, a lone gunman shot multiple people on the campus of
      Northern Illinois University in DeKalb, Illinois, killing 5 and wounding 21. As
      part of an ongoing longitudinal study on that campus, a cohort of female
      undergraduate students, interviewed prior to the shooting, completed follow-up
      trauma-related measures including PTSD symptom severity (follow-up survey was
      launched 17 days postshooting; n = 691). To obtain DNA, salivary samples were
      collected from a subset of the original study population based on willingness to
      participate (n = 276). PARTICIPANTS: Two hundred four undergraduate women. MAIN
      OUTCOME MEASURES: SLC6A4 polymorphisms STin2, 5-HTTLPR, and rs25531 were
      genotyped in 235 individuals. RESULTS: We found that although the STin2 variant
      and 5-HTTLPR alone did not associate with increased PTSD symptoms, rs25531 and
      the 5-HTTLPR multimarker genotype (combined 5-HTTLPR and rs25531) were associated
      with significantly increased acute stress disorder symptoms at 2 to 4 weeks
      postshooting (n = 161; P < .05). This association remained significant when
      controlling for race and for level of shooting exposure (n = 123; P < .007). The
      association was most robust with the 5-HTTLPR multimarker genotype and avoidance
      symptoms (P = .003). CONCLUSION: These data suggest that differential function of
      the serotonin transporter may mediate differential response to a severe trauma.
      When examined in a relatively homogenous sample with shared trauma and known
      prior levels of child and adult trauma, the 5-HTTLPR multimarker genotype may
      serve as a useful predictor of risk for PTSD-related symptoms in the weeks and
      months following the trauma.

PMID- 21893642
TI  - Molecular and genetic evidence for abnormalities in the nodes of Ranvier in
      schizophrenia.
AB  - CONTEXT: Genetic, neuroimaging, and molecular neurobiological evidence support
      the hypothesis that the disconnectivity syndrome in schizophrenia (SZ) could
      arise from failures of saltatory conduction and abnormalities at the nodes of
      Ranvier (NOR) interface where myelin and axons interact. OBJECTIVE: To identify
      abnormalities in the expression of oligodendroglial genes and proteins that
      participate in the formation, maintenance, and integrity of the NOR in SZ.
      DESIGN: The messenger RNA (mRNA) expression levels of multiple NOR genes were
      quantified in 2 independent postmortem brain cohorts of individuals with SZ, and
      generalizability to protein expression was confirmed. The effect of the ANK3
      genotype on the mRNA expression level was tested in postmortem human brain. Case
      control analysis tested the association of the ANK3 genotype with SZ. The ANK3
      genotype's influence on cognitive task performance and functional magnetic
      resonance imaging activation was tested in 2 independent cohorts of healthy
      individuals. SETTING: Research hospital. Patients  Postmortem samples from
      patients with SZ and healthy controls were used for the brain expression study (n
      = 46) and the case-control analysis (n = 272). Healthy white men and women
      participated in the cognitive (n = 513) and neuroimaging (n = 52) studies. MAIN
      OUTCOME MEASURES: The mRNA and protein levels in postmortem brain samples,
      genetic association with schizophrenia, cognitive performance, and blood
      oxygenation level-dependent functional magnetic resonance imaging. RESULTS: The
      mRNA expression of multiple NOR genes was decreased in schizophrenia. The ANK3
      rs9804190 C allele was associated with lower ANK3 mRNA expression levels, higher
      risk for SZ in the case-control cohort, and poorer working memory and executive
      function performance and increased prefrontal activation during a working memory
      task in healthy individuals. CONCLUSIONS: These results point to abnormalities in
      the expression of genes and protein associated with the integrity of the NOR and
      suggest them as substrates for the disconnectivity syndrome in SZ. The
      association of ANK3 with lower brain mRNA expression levels implicates a
      molecular mechanism for its genetic, clinical, and cognitive associations with
      SZ.

PMID- 21893643
TI  - Emergency treatment of deliberate self-harm.
AB  - CONTEXT: Although concern exists over the quality of emergency mental health
      services, little is known about the mental health care of adults who are admitted
      to emergency departments for deliberately harming themselves and then discharged
      to the community. OBJECTIVE: To describe the predictors of emergency department
      discharge, the emergency mental health assessments, and the follow-up outpatient
      mental health care of adult Medicaid beneficiaries treated for deliberate self
      harm. DESIGN: A retrospective longitudinal cohort analysis. SETTING: National
      Medicaid claims data supplemented with county-level sociodemographic variables
      and Medicaid state policy survey data. PARTICIPANTS: Adults aged 21 to 64 years
      who were treated in emergency departments for 7355 episodes of deliberate self
      harm, focusing on those who were discharged to the community (4595 episodes).
      MAIN OUTCOME MEASURES: Rates and adjusted risk ratios (ARRs) of discharge to the
      community, mental health assessments in the emergency department, and outpatient
      mental health visits during the 30 days following the emergency department visit.
      RESULTS: Most patients (62.5%) were discharged to the community. Emergency
      department discharge was directly related to younger patient age (21-31 years vs
      45-64 years) (ARR, 1.18 [99% confidence interval {CI}, 1.10-1.25]) and self-harm
      by cutting (ARR, 1.18 [99% CI, 1.12-1.24]) and inversely related to poisoning
      (ARR, 0.84 [99% CI, 0.80-0.89]) and recent psychiatric hospitalization (ARR, 0.74
      [99% CI, 0.67-0.81]). Approximately one-half of discharged patients (47.5%)
      received a mental health assessment in the emergency department, and a similar
      percentage of discharged patients (52.4%) received a follow-up outpatient mental
      health visit within 30 days. Follow-up mental health care was directly related to
      recent outpatient mental health care (ARR, 2.30 [99% CI, 2.11-2.50]) and
      treatment in a state with Medicaid coverage of mental health clinic services
      (ARR, 1.13 [99% CI, 1.05-1.22]) and inversely related to African American (ARR,
      0.86 [99% CI, 0.75-0.96]) and Hispanic (ARR, 0.86 [99% CI, 0.75-0.99])
      race/ethnicity. CONCLUSION: Most adult Medicaid beneficiaries who present for
      emergency care for deliberate self-harm are discharged to the community, and many
      do not receive emergency mental health assessments or follow-up outpatient mental
      health care.

PMID- 21893644
TI  - Pediatrics tackles child sexual abuse.

PMID- 21893645
TI  - Paternal vs maternal kangaroo care for procedural pain in preterm neonates: a
      randomized crossover trial.
AB  - OBJECTIVE: To test paternal vs maternal kangaroo care (KC) to reduce pain from
      heel lance. DESIGN: Randomized crossover design. SETTING: Three university
      affiliated level III neonatal intensive care units. PATIENTS: Sixty-two preterm
      neonates at 28 to 36 weeks' gestational age who were expected to stay in the
      neonatal intensive care unit for at least 2 blood sampling procedures, without
      major congenital anomalies, grade III or IV intraventricular hemorrhage, or
      periventricular leukomalacia; without surgical interventions; not receiving
      parenteral analgesics or sedatives within 72 hours; and with parental consent.
      INTERVENTION: During 2 separate medically ordered heel lance procedures at least
      24 hours apart, infants were held in KC for 30 minutes before and during the
      procedure with the mother or with the father, and with the other parent in the
      subsequent session. Which parent came first was randomized. MAIN OUTCOME
      MEASURES: The Premature Infant Pain Profile and time for heart rate to return to
      baseline were the primary outcomes. RESULTS: At 30 and 60 seconds after the heel
      lance, infants in maternal KC displayed significantly lower scores on the
      Premature Infant Pain Profile than when in paternal KC (30 seconds mean
      difference, 1.435 [95% confidence interval, 0.232-2.632]); 60 seconds mean
      difference, 1.548 [95% confidence interval, 0.069-3.027]). At 90 and 120 seconds,
      there were no differences. The difference in time to return to KC heart rate
      before the heel lance was significant, with the time in maternal KC being 204
      seconds and in paternal KC, 246 seconds (mean difference, 42 seconds [95%
      confidence interval, 5.16-81.06 seconds]). CONCLUSIONS: Mothers were marginally
      more effective than fathers in decreasing pain response. Future research should
      address feasibility issues and nonparent providers of KC during painful
      procedures. TRIAL REGISTRATION: clinicaltrials.gov Identifier: ISRCTN51481987.

PMID- 21893646
TI  - Relationship between weekend catch-up sleep and poor performance on attention
      tasks in Korean adolescents.
AB  - OBJECTIVE: To investigate the relationship between insufficient sleep and poor
      attention in Korean adolescents, adjusting for potential confounding factors of
      depressed mood and habitual snoring. DESIGN: School-based cross-sectional study.
      SETTING: Eight high schools in 3 cities in the Republic of Korea. PARTICIPANTS: A
      sample of 2638 urban high school students (42.2% male and 57.8% female; mean [SD]
      age, 17.3 [0.6] years [age range, 14-19 years]) completed questionnaires and
      computerized attention tasks during the school term. EXPOSURE: Weekend catch-up
      sleep. MAIN OUTCOME MEASURES: Self-reported sleep schedules and habits, including
      sleep duration, bedtime, wake-up time, depressed mood, and habitual snoring. Also
      measured were numbers of omission and commission errors on computerized attention
      tasks. RESULTS: The mean (SD) sleep duration on weekdays was 5 hours 42 minutes
      (1 hour 0 minutes) per day and on weekends was 8 hours 24 minutes (1 hour 36
      minutes) per day. The mean (SD) weekend catch-up sleep was 2 hours 42 minutes (1
      hour 42 minutes) per day. After adjusting for age, sex, depressed mood (Beck
      Depression Inventory score, >=10), habitual snoring, and weekday sleep duration,
      increased weekend catch-up sleep was significantly associated with more omission
      and commission errors on sustained attention tasks (P < .001 and P = .03,
      respectively) and on divided attention tasks (P = .01 and P = .04, respectively).
      CONCLUSIONS: Increased weekend catch-up sleep as an indicator of insufficient
      weekday sleep is associated with poor performance on objective attention tasks.
      Assessment of catch-up sleep and sleep duration may be useful for physicians to
      evaluate sleep insufficiency and its adverse effects on attention in adolescents.

PMID- 21893647
TI  - Compliance with recommendations and opportunities for vaccination at ages 11 to
      12 years: evaluation of the 2009 national immunization survey-teen.
AB  - OBJECTIVES: To determine vaccination coverage at selected ages and by birth
      cohort and to assess whether all indicated vaccines were administered during
      vaccination visits. DESIGN: Population-based cross-sectional study. SETTING:
      National Immunization Survey-Teen 2009 telephone interview. PARTICIPANTS: United
      States adolescents aged 13 to 17 years with provider-reported vaccination
      histories (N = 20 066). MAIN OUTCOME MEASURES: Among all adolescents and by birth
      cohort: coverage estimates for 3 childhood vaccines (measles-containing,
      hepatitis B, and varicella) and 3 adolescent vaccines (tetanus-diphtheria and/or
      tetanus-diphtheria-acellular pertussis, meningococcal-containing, and human
      papillomavirus for girls) at selected ages. RESULTS: By age 11 years, most
      adolescents had obtained the childhood vaccines. Receipt of a tetanus-diphtheria
      and/or tetanus-diphtheria-acellular pertussis vaccine at ages 11 to 12 years
      increased significantly from the 1991 to 1996 birth cohort (33.8% vs 68.2%, P <
      .001); receipt of meningococcal-containing vaccine at ages 11 to 12 years
      increased significantly from the 1993 to 1996 birth cohort (8.4% vs 50.0%, P <
      .001). Among girls, receipt of human papillomavirus vaccine at ages 11 to 12
      years increased significantly from the 1994 to 1996 birth cohort (11.1% vs 30.5%,
      P < .001). Overall, 54.9% of adolescents received at least 1 vaccination visit at
      ages 11 to 12 years. Among adolescents who made a vaccination visit at ages 11 to
      12 years and were eligible for vaccination, 19.5% did not receive tetanus
      diphtheria and/or tetanus-diphtheria-acellular pertussis, 60.9% did not receive
      meningococcal-containing, and 62.4% did not receive human papillomavirus
      vaccines. CONCLUSIONS: Receipt of vaccines at the recommended ages of 11 to 12
      years appears to be increasing; however, providers often do not administer all
      indicated vaccines during a vaccination visit.

PMID- 21893648
TI  - Learning problems in kindergarten students with extremely preterm birth.
AB  - OBJECTIVES: To assess learning problems among kindergarten students with
      extremely preterm birth and to identify risk factors. DESIGN: Cohort study.
      SETTING: Children's hospital. PARTICIPANTS: A cohort of 148 children born between
      January 1, 2001, and December 31, 2003, with extremely preterm birth, defined as
      less than 28 weeks' gestation or having a birth weight of less than 1000 g, and
      111 classmate control individuals born at term with normal birth weight.
      INTERVENTIONS: The children were enrolled in the study during their first year in
      kindergarten and were assessed on measures of learning progress. MAIN OUTCOME
      MEASURES: Achievement testing, teacher ratings of learning progress, and
      individual educational assistance. RESULTS: Children with extremely preterm birth
      had lower mean standard scores than controls on achievement tests of spelling
      (8.52; 95% confidence interval, 4.58-12.46) and applied mathematics (11.02; 6.76
      15.28). They had higher rates of substandard learning progress by teacher report
      in written language (odds ratio, 4.23; 95% CI, 2.32-7.73) and mathematics (7.08;
      2.79-17.95). Group differences in mathematics achievement and in teacher ratings
      of learning progress were statistically significant even in children without
      neurosensory deficits or low global cognitive ability. Neonatal risk factors,
      early childhood neurodevelopmental impairment, and socioeconomic status predicted
      learning problems in children with extremely preterm birth; however, many
      children with problems were not enrolled in a special education program.
      CONCLUSIONS: Learning problems in children with extremely preterm birth are
      evident in kindergarten and are associated with neonatal and early childhood risk
      factors. Our findings support efforts to provide more extensive monitoring and
      interventions before and during the first year of school.

PMID- 21893649
TI  - Controller medication use and sleep problems in pediatric asthma: a longitudinal
      case-crossover analysis.
AB  - OBJECTIVE: To determine the effect of asthma controller medication use, choice,
      and adherence on sleep in children with asthma. DESIGN: A case-crossover analysis
      examining within-subject differences in controller use between time points with
      and without sleep problems, based on survey data from 3 time points (baseline, 6
      months, and 1 year) of a randomized trial. SETTING: Families were recruited from
      2 area practice networks; all assessments were completed by parents online.
      PARTICIPANTS: Children with asthma, aged 2 to 10 years, as identified by asthma
      related medical encounters and prescription fills. MAIN EXPOSURES: Parent report
      of asthma controller medication use (yes/no), type (inhaled corticosteroid or
      leukotriene inhibitor), and adherence (daily use, nonadherent use, or nonuse).
      MAIN OUTCOME MEASURES: Children's sleep problems, as defined by parent report
      regarding how often the child had difficulty falling asleep or experienced
      daytime sleepiness. RESULTS: The analysis included 482 children; 82.6% and 75.9%
      completed the 6-month and 1-year follow-up visits, respectively. Sleep problems
      were common, with 19.4% of parents at baseline reporting frequent problems with
      the child falling asleep and 12.1% reporting frequent daytime sleepiness.
      Compared with children who did not use a controller medication, children had a
      decreased risk of problems falling asleep during periods with daily controller
      use (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.13-0.92), with a
      trend toward an effect in those with nonadherent use (0.47; 0.20-1.12). Any
      controller use, regardless of adherence, was also associated with decreased odds
      of daytime sleepiness (OR, 0.69; 95% CI, 0.51-0.94). When controller class was
      examined, leukotriene inhibitors were associated with significantly decreased
      odds of problems falling asleep (OR, 0.18; 95% CI, 0.04-0.78), with or without
      concomitant use of inhaled corticosteroids, but the results for use of inhaled
      corticosteroids alone were not statistically significant (0.69; 0.32-1.53).
      CONCLUSIONS: Controller medications appear to be effective in reducing sleep
      problems in children with asthma, and leukotriene inhibitor medications may be
      especially effective in this population.

PMID- 21893651
TI  - Patient volume and quality of care for young children hospitalized with acute
      gastroenteritis.
AB  - OBJECTIVE: To explore the relationship between the volume of children admitted to
      the hospital with acute gastroenteritis and adherence to recommended quality
      indicators. DESIGN: Retrospective cohort study. SETTING: Premier Perspective
      clinical and financial information systems database (Premier Inc, Charlotte,
      North Carolina). PARTICIPANTS: A total of 12,604 otherwise healthy children aged
      3 months to 10 years hospitalized between January 1, 2007, and December 31, 2009,
      at 280 US hospitals with International Classification of Diseases, Ninth Revision
      diagnosis codes indicating acute gastroenteritis. MAIN EXPOSURE: Volume of
      hospital admissions per year of children with acute gastroenteritis. MAIN OUTCOME
      MEASURES: Quality indicators for overuse and misuse of care in the management of
      acute gastroenteritis based on nationally published guidelines. These include
      blood testing, stool studies, use of antibiotics, and use of nonrecommended
      antiemetic or antidiarrheal medications (hereafter referred to as nonrecommended
      medications). RESULTS: Selected blood, stool, and rotavirus tests (overuse
      indicators) were performed in 85%, 46%, and 56% of children, respectively. Six
      percent of children received nonrecommended medications, and 26% received
      antibiotics (misuse indicators). Higher volumes of hospital admission for acute
      gastroenteritis were associated with less use of blood tests (odds ratio [OR],
      0.67 [95% confidence interval {CI}, 0.50-0.89]), nonrecommended medications (OR,
      0.84 [95% CI, 0.76-0.93]), and antibiotics (OR, 0.93 [95% CI, 0.86-0.99]).
      Children admitted to hospitals in the 25th vs 75th percentile of patient volume
      had a 10%, 30%, and 10% increased chance of having blood tests, nonrecommended
      medications, and antibiotics ordered, respectively. CONCLUSIONS: In a nationally
      representative sample of hospitals that care for children with acute
      gastroenteritis, higher patient volumes were associated with greater adherence to
      established quality indicators. Further investigation is needed to identify the
      hospital characteristics driving the volume-quality relationship for this common
      pediatric condition.

PMID- 21893652
TI  - Picture of the month--quiz case. Plastic bronchitis.

PMID- 21893653
TI  - What have we learned about early treatment of Pseudomonas aeruginosa infection in
      infants and children with cystic fibrosis?

PMID- 21893654
TI  - How parents can help children cope with procedures and pain.

PMID- 21893650
TI  - Comparative efficacy and safety of 4 randomized regimens to treat early
      Pseudomonas aeruginosa infection in children with cystic fibrosis.
AB  - OBJECTIVE: To investigate the efficacy and safety of 4 antipseudomonal treatments
      in children with cystic fibrosis with recently acquired Pseudomonas aeruginosa
      infection. DESIGN: Randomized controlled trial. SETTING: Multicenter trial in the
      United States. PARTICIPANTS: Three hundred four children with cystic fibrosis
      aged 1 to 12 years within 6 months of P aeruginosa detection. INTERVENTIONS:
      Participants were randomized to 1 of 4 antibiotic regimens for 18 months (six 12
      week quarters) between December 2004 and June 2009. Participants randomized to
      cycled therapy received tobramycin inhalation solution (300 mg twice a day) for
      28 days, with oral ciprofloxacin (15-20 mg/kg twice a day) or oral placebo for 14
      days every quarter, while participants randomized to culture-based therapy
      received the same treatments only during quarters with positive P aeruginosa
      cultures. MAIN OUTCOME MEASURES: The primary end points were time to pulmonary
      exacerbation requiring intravenous antibiotics and proportion of P aeruginosa 
      positive cultures. RESULTS: The intention-to-treat analysis included 304
      participants. There was no interaction between treatments. There were no
      statistically significant differences in exacerbation rates between cycled and
      culture-based groups (hazard ratio, 0.95; 95% confidence interval [CI], 0.54
      1.66) or ciprofloxacin and placebo (hazard ratio, 1.45; 95% CI, 0.82-2.54). The
      odds ratios of P aeruginosa- positive culture comparing the cycled vs culture
      based group were 0.78 (95% CI, 0.49-1.23) and 1.10 (95% CI, 0.71-1.71) comparing
      ciprofloxacin vs placebo. Adverse events were similar across groups. CONCLUSIONS:
      No difference in the rate of exacerbation or prevalence of P aeruginosa
      positivity was detected between cycled and culture-based therapies. Adding
      ciprofloxacin produced no benefits. TRIAL REGISTRATION: ClinicalTrials.gov
      Identifier: NCT00097773.

PMID- 21893655
TI  - Chauvet cave: the Panel of Horses.

PMID- 21893656
TI  - Changes in cortical thickness during the course of illness in schizophrenia.
AB  - CONTEXT: Whether cortical thickness changes in schizophrenia over time are more
      pronounced relative to the changes that can be attributed to normal aging has not
      been studied. OBJECTIVE: To compare patients with schizophrenia and healthy
      control participants on cortical thickness change. DESIGN: A 5-year longitudinal
      study comparing schizophrenic patients and healthy controls using 2 magnetic
      resonance images of the brain. SETTING: Patients were recruited from the
      Department of Psychiatry at the University Medical Centre Utrecht and from other
      psychiatric hospitals in the Netherlands. Healthy controls were recruited via
      advertisement in newspapers and notice boards. PARTICIPANTS: Ninety-six
      schizophrenic patients and 113 healthy controls aged 16 to 56 years. MAIN OUTCOME
      MEASURES: Cortical thickness and change in cortical thickness on a vertex-by
      vertex basis across the cortical mantle, measures of functional and symptomatic
      outcome, and cumulative intake of antipsychotics during the scan interval.
      RESULTS: At baseline, the schizophrenic patients had thinner left orbitofrontal
      and right parahippocampal and superior temporal cortices and a thicker superior
      parietal lobule and occipital pole compared with the controls. Mean cortical
      thickness did not differ between the groups. Over time, excessive cortical
      thinning was found in widespread areas on the cortical mantle, most pronounced
      bilaterally in the temporal cortex and in the left frontal area. Poor outcome in
      patients was associated with more pronounced cortical thinning. Higher cumulative
      intake of typical antipsychotics during the scan interval was associated with
      more pronounced cortical thinning, whereas higher cumulative intake of atypical
      antipsychotic medication was associated with less pronounced cortical thinning.
      CONCLUSIONS: In schizophrenia, the cortex shows excessive thinning over time in
      widespread areas of the brain, most pronounced in the frontal and temporal areas,
      and progresses across the entire course of the illness. The excessive thinning of
      the cortex appears related to outcome and medication intake.

PMID- 21893657
TI  - The effect of early trauma exposure on serotonin type 1B receptor expression
      revealed by reduced selective radioligand binding.
AB  - CONTEXT: Serotonergic dysfunction is implicated in the pathogenesis of
      posttraumatic stress disorder (PTSD), and recent animal models suggest that
      disturbances in serotonin type 1B receptor function, in particular, may
      contribute to chronic anxiety. However, the specific role of the serotonin type
      1B receptor has not been studied in patients with PTSD. OBJECTIVE: To investigate
      in vivo serotonin type 1B receptor expression in individuals with PTSD, trauma
      exposed control participants without PTSD (TC), and healthy (non-trauma-exposed)
      control participants (HC) using positron emission tomography and the recently
      developed serotonin type 1B receptor selective radiotracer [(11)C]P943. DESIGN:
      Cross-sectional positron emission tomography study under resting conditions.
      SETTING: Academic and Veterans Affairs medical centers. PARTICIPANTS: Ninety-six
      individuals in 3 study groups: PTSD (n = 49), TC (n = 20), and HC (n = 27). Main
      Outcome Measure  Regional [(11)C]P943 binding potential (BP(ND)) values in an a
      priori-defined limbic corticostriatal circuit investigated using multivariate
      analysis of variance and multiple regression analysis. RESULTS: A history of
      severe trauma exposure in the PTSD and TC groups was associated with marked
      reductions in [(11)C]P943 BP(ND) in the caudate, the amygdala, and the anterior
      cingulate cortex. Participant age at first trauma exposure was strongly
      associated with low [(11)C]P943 BP(ND). Developmentally earlier trauma exposure
      also was associated with greater PTSD symptom severity and major depression
      comorbidity. CONCLUSIONS: These data suggest an enduring effect of trauma history
      on brain function and the phenotype of PTSD. The association of early age at
      first trauma and more pronounced neurobiological and behavioral alterations in
      PTSD suggests a developmental component in the cause of PTSD.

PMID- 21893658
TI  - Grief in children and adolescents bereaved by sudden parental death.
AB  - CONTEXT: Major advances have been made in our understanding of the phenomenology
      and course of grief in adults. However, little is known about the course of grief
      in children and adolescents. OBJECTIVE: We report on the course of children's and
      adolescents' grief reactions after sudden parental death and the effect of those
      reactions on subsequent psychiatric and functional status. DESIGN: Longitudinal
      study (July 1, 2002, through January 16, 2007) of bereaved children, adolescents,
      and families, with yearly comprehensive assessments as long as 3 years after
      parental death. SETTING: Bereaved children and adolescents and their surviving
      parents recruited through coroners' records and a newspaper advertisement.
      PARTICIPANTS: A total of 182 parentally bereaved children and adolescents aged 7
      through 18 years whose parent died due to suicide, unintentional injury, or
      sudden natural causes. MAIN OUTCOME MEASURES: Grief, functional impairment, and
      incident depression. RESULTS: Three distinct trajectories of grief reactions were
      observed in the study participants. In 1 group, which consisted of 10.4% of the
      sample, grief reactions showed no change 33 months after death. Children and
      adolescents with prolonged grief reactions had higher rates of previous personal
      history of depression. Prolonged grief made unique contributions to increased
      levels of functional impairment, even after controlling for the clinical
      characteristics before and after the death. Conversely, prolonged grief in
      children, adolescents, and the surviving caregiver predisposed children and
      adolescents to an increased hazard of incident depression. Another group (30.8%)
      showed increased grief reactions 9 months after the death, which gradually
      decreased over time. Despite this finding, grief reactions in this group also
      were associated with functional impairment and increased risk of incident
      depression. CONCLUSIONS: Grief reactions abate over time for most children and
      adolescents bereaved by sudden parental death; however, a subset shows increased
      or prolonged grief reactions, which in turn increases the risk of functional
      impairment and depression. Research regarding interventions designed to relieve
      the burden of grief in bereaved children and adolescents are needed. Such efforts
      also should assess and address grief reactions in the surviving parent.

PMID- 21893659
TI  - Bereavement-related depressive episodes: characteristics, 3-year course, and
      implications for the DSM-5.
AB  - CONTEXT: The DSM-IV criteria for major depressive episodes exclude brief episodes
      that are better accounted for by bereavement. However, a proposal has been made
      to remove this exclusion from the DSM-5. OBJECTIVES: To compare the demographic
      and psychiatric characteristics of participants with bereavement-related, single,
      brief (<2 months) depressive episodes and other types of depressive episodes and
      to compare the future risk of depression between these groups and participants
      without a history of depression at baseline. DESIGN: A longitudinal, community
      based, epidemiologic study conducted from August 1, 2001, through May 31, 2002
      (wave 1), and from August 1, 2004, through September 30, 2005 (wave 2). SETTING:
      The US general population, including residents of Hawaii and Alaska.
      PARTICIPANTS: Participants in the National Epidemiologic Survey on Alcohol and
      Related Conditions waves 1 (n = 43 093) and 2 (n = 34 653). MAIN OUTCOME
      MEASURES: Demographic characteristics, age at onset, history of depression in
      first-degree relatives, impairment in role functioning, psychiatric
      comorbidities, lifetime mental health service use, and new depressive episodes
      during the 3-year follow-up period. RESULTS: Compared with participants with
      other types of depression, those with bereavement-related, single, brief
      depressive episodes were more likely to experience later onset and to be black
      but less likely to have had impairment in role functioning, comorbid anxiety
      disorders, or a treatment history at baseline. Participants with bereavement
      related, single, brief episodes were less likely than those with bereavement
      unrelated, single, brief episodes to experience fatigue, increased sleep,
      feelings of worthlessness, and suicidal ideations. The risk of new depressive
      episodes during the follow-up period among participants with bereavement-related,
      single, brief episodes was significantly lower than among participants with
      bereavement-unrelated, single, brief episodes and other types of depression but
      similar to the risk among the participants from the general population with no
      baseline history of depression. CONCLUSIONS: Bereavement-related, single, brief
      depressive episodes have distinct demographic and symptom profiles compared with
      other types of depressive episodes and are not associated with increased risk of
      future depression. The findings support preserving the DSM-IV bereavement
      exclusion criterion for major depressive episodes in the DSM-5.

PMID- 21893660
TI  - Suicide categories by patterns of known risk factors: a latent class analysis.
AB  - CONTEXT: Multiple risk factors contribute to suicides; however, patterns of co
      occurrence among these factors have not been fully identified. OBJECTIVES: To
      assess patterns of known suicide-related risk factors, classify suicide decedents
      by these patterns, track class proportions during a 6-year period, and
      characterize decedents across the classes to help focus prevention strategies.
      DESIGN, SETTING, AND PARTICIPANTS: Latent class analysis was conducted using 2003
      2008 data from the National Violent Death Reporting System. The population
      included 28 703 suicide decedents from 12 US states. MAIN OUTCOME MEASURES: The
      known risk factors included having the following: mental health conditions; a sad
      or depressed mood; substance abuse problems; medical problems; recent crises;
      financial, job, and legal problems; intimate partner and other relationship
      problems; and perpetrated interpersonal violence. RESULTS: Nine distinct patterns
      of risk factors emerged. Of these classes, 1 only endorsed mental health-related
      factors and 1 only endorsed alcohol- and substance abuse-related factors;
      however, 7 classes of decedents had distinct patterns of factors that spanned
      multiple domains. For example, 5 of these classes had mental health factors with
      other risks (eg, substance abuse, financial problems, relationship problems, a
      recent crisis, and medical problems). Two classes had recent crises with
      relationship problems; one of these classes also had high probabilities for
      criminal problems and interpersonal violence. Class proportions differed during
      the 6 years. Differences across classes by demographic and event characteristics
      were also found. CONCLUSIONS: Most suicide decedents could be classified by
      patterns of risk factors. Furthermore, most classes revealed a need for more
      connected services across medical, mental health/substance abuse, and
      court/social service systems. Reducing fragmentation across these agencies and
      recruiting family, friend, and community support for individuals experiencing
      mental health problems and/or other stress might significantly reduce suicides.

PMID- 21893661
TI  - Utility of combinations of biomarkers, cognitive markers, and risk factors to
      predict conversion from mild cognitive impairment to Alzheimer disease in
      patients in the Alzheimer's disease neuroimaging initiative.
AB  - CONTEXT: Biomarkers have become increasingly important in understanding
      neurodegenerative processes associated with Alzheimer disease. Markers include
      regional brain volumes, cerebrospinal fluid measures of pathological Abeta1-42
      and total tau, cognitive measures, and individual risk factors. OBJECTIVE: To
      determine the discriminative utility of different classes of biomarkers and
      cognitive markers by examining their ability to predict a change in diagnostic
      status from mild cognitive impairment to Alzheimer disease. DESIGN: Longitudinal
      study. PARTICIPANTS: We analyzed the Alzheimer's Disease Neuroimaging Initiative
      database to study patients with mild cognitive impairment who converted to
      Alzheimer disease (n = 116) and those who did not convert (n = 204) within a 2
      year period. We determined the predictive utility of 25 variables from all
      classes of markers, biomarkers, and risk factors in a series of logistic
      regression models and effect size analyses. SETTING: The Alzheimer's Disease
      Neuroimaging Initiative public database. OUTCOME MEASURES: Primary outcome
      measures were odds ratios, pseudo- R(2)s, and effect sizes. RESULTS: In
      comprehensive stepwise logistic regression models that thus included variables
      from all classes of markers, the following baseline variables predicted
      conversion within a 2-year period: 2 measures of delayed verbal memory and middle
      temporal lobe cortical thickness. In an effect size analysis that examined rates
      of decline, change scores for biomarkers were modest for 2 years, but a change in
      an everyday functional activities measure (Functional Assessment Questionnaire)
      was considerably larger. Decline in scores on the Functional Assessment
      Questionnaire and Trail Making Test, part B, accounted for approximately 50% of
      the predictive variance in conversion from mild cognitive impairment to Alzheimer
      disease. CONCLUSIONS: Cognitive markers at baseline were more robust predictors
      of conversion than most biomarkers. Longitudinal analyses suggested that
      conversion appeared to be driven less by changes in the neurobiologic trajectory
      of the disease than by a sharp decline in functional ability and, to a lesser
      extent, by declines in executive function.

PMID- 21893663
TI  - Posttraumatic stress disorder subtypes invalid.

PMID- 21893662
TI  - Temporal relationship between depression and dementia: findings from a large
      community-based 15-year follow-up study.
AB  - CONTEXT: Late-life depression is associated with increased risk of dementia, but
      the temporal relationship between depression and development of dementia remains
      unclear. OBJECTIVES: To examine the association between risk of dementia and
      baseline depressive symptoms; history of depression, particularly early-life (<50
      years) vs late-life depression (>=50 years); and individual domains of the Center
      for Epidemiologic Studies Depression Scale. DESIGN: A large cohort with initially
      nondemented participants was followed up biennially for up to 15 years. Baseline
      depressive symptoms were assessed using the 11-item version of the Center for
      Epidemiologic Studies Depression Scale; presence of significant depressive
      symptoms was defined as a score of 11 or greater. Self-reported history of
      depression was collected at the baseline interview. Cox proportional hazards
      regression was used to assess the association between depression and dementia
      risk. SETTING: Population-based cohort drawn from members of the Group Health
      Cooperative in Seattle, Washington. PARTICIPANTS: A cohort of 3410 participants
      without dementia aged at least 65 years. RESULTS: During a mean of 7.1 years of
      follow-up, 658 participants (19.3%) developed dementia. At baseline, 9.4% of
      participants had presence of significant depressive symptoms, and 21.2% reported
      a history of depression. The adjusted hazard ratio for dementia associated with
      baseline depressive symptoms was 1.71 (95% confidence interval, 1.37-2.13), after
      adjusting for age at entry, sex, educational level, and wave of enrollment.
      Compared with participants without depression history, those with late-life
      depression were at increased dementia risk (adjusted hazard ratio, 1.46; 95%
      confidence interval, 1.16-1.84), but early-life depression had no association
      with dementia risk (1.10 [0.83-1.47]). Depressed mood (adjusted hazard ratio,
      1.48; 95% confidence interval, 1.25-1.76) and perceived performance difficulty
      (1.39 [1.15-1.67]) were independently associated with dementia. CONCLUSION: This
      study confirmed that late-life depression is associated with increased risk of
      dementia and supplied evidence that late-life depression may be an early
      manifestation of dementia rather than increasing risk for dementia.

PMID- 21893664
TI  - Pearls & oy-sters: status epilepticus from hyperammonemia after lung transplant.

PMID- 21893666
TI  - Teaching neuroimages: excessive fragmentary hypnic myoclonus.

PMID- 21893665
TI  - Teaching neuroimages: punctuate and curvilinear enhancement peppering the pons
      responsive to steroids.

PMID- 21893667
TI  - Neurology (1997-2006): "A man's reach must exceed his grasp"--from Andrea del
      Sarto, Robert Browning.

PMID- 21893668
TI  - Psychogenic nonepileptic seizures in US veterans.
AB  - OBJECTIVES: Psychogenic nonepileptic seizures (PNES) are frequently encountered
      in epilepsy monitoring units (EMU) and can result in significant long-term
      disability. We reviewed our experience with veterans undergoing seizure
      evaluation in the EMU to determine the time delay to diagnosis of PNES, the
      frequency of PNES, and cumulative antiepileptic drug (AED) treatment. We compared
      veterans with PNES to civilians with PNES studied in the same EMU. METHODS: We
      reviewed records of all patients admitted to one Veterans Affairs Medical Center
      (VAMC) EMU over a 10-year interval. These patients included 203 veterans and 726
      civilians from the university affiliate. The percentage of patients with PNES was
      calculated for the veteran and civilian groups. Fifty veterans with only PNES
      were identified. Each veteran with PNES was matched to the next civilian patient
      with PNES. The 2 groups were compared for interval from onset of the habitual
      spells to EMU diagnosis, cumulative AED treatment, and other measures. RESULTS:
      PNES were identified in 25% of veterans and 26% of civilians admitted to the EMU.
      The delay from onset of spells to EMU diagnosis averaged 60.5 months for veterans
      and 12.5 months for civilians (p < 0.001). Cumulative AED treatment was 4 times
      greater for veterans with PNES as compared to civilians (p < 0.01). Fifty-eight
      percent of veterans with PNES were thought to have seizures related to traumatic
      brain injury. CONCLUSIONS: The results indicate a substantial delay in the
      diagnosis of PNES in veterans as compared to civilians. The delay is associated
      with greater cumulative AED treatment.

PMID- 21893670
TI  - Depiction of the neuroscientific principles of human motion 2 millennia ago by
      Lucretius.
AB  - Titus Lucretius Carus was an ancient Roman philosopher of the Epicurean school
      whose epic poem On the Nature of Things described numerous aspects of the natural
      world. In fact, much contemporary scientific understanding is consistent with or
      inspired by his work. Among Lucretius's contributions to neurology were his
      descriptions of epileptic seizures, sleep, and his theory of vision. This report
      identifies how Lucretius's description of human motion recognized the fundamental
      principles understood by contemporary neurologists and neuroscientists, namely
      the importance of the mind and intelligence in determining whether to move, in
      the initiation of motion and its effect on the rest of the body; the importance
      of mental imagery and perception of the motor task's nature and workload in
      addition to the necessary systemic changes occurring in parallel with the muscle
      activity. Lucretius was the first commentator to introduce into Epicurean poetry
      the concept of such a mechanism consisting of a logical order of processes which
      are still consistent with modern concepts.

PMID- 21893671
TI  - Comment: Lucretius and the epicurean neurologist.

PMID- 21893672
TI  - Incidence of epilepsy: a systematic review and meta-analysis.
AB  - OBJECTIVE: To estimate the pooled incidence of epilepsy from published studies
      and investigate sources of heterogeneity in the estimates. METHODS: We searched
      online databases for incidence studies and used meta-analytic methods to analyze
      the data. RESULTS: Thirty-three articles met the entry criteria. The median
      incidence of epilepsy was 50.4/100,000/year (interquartile range [IQR] 33.6
      75.6), while it was 45.0 (IQR 30.3-66.7) for high-income countries and 81.7 (IQR
      28.0-239.5) for low- and middle-income countries. Population-based studies had
      higher incidence estimates than hospital-based studies (p = 0.02) while
      retrospective study design was associated with lower estimates than prospective
      studies (p = 0.04). CONCLUSION: We provide data that could potentially be used to
      assess the burden and analyze the trends in incidence of epilepsy. Our results
      support the need for large population-based incidence studies of epilepsy.

PMID- 21893673
TI  - The forgotten nails: hemionychophagia.

PMID- 21893674
TI  - Pearls & oy-sters: a distinctive watershed area in the vertebrobasilar territory.

PMID- 21893675
TI  - First-order Horner syndrome due to ipsilateral thalamic hemorrhage.

PMID- 21893676
TI  - Indolent course of progressive multifocal leukoencephalopathy during natalizumab
      treatment in MS.

PMID- 21893677
TI  - Objective assessment of increase in breathing resistance of N95 respirators on
      human subjects.
AB  - Face masks or respirators are commonly worn by medical professionals and patients
      for protection against respiratory tract infection and the spread of illnesses,
      such as severe acute respiratory syndrome and pandemic influenza (H1N1).
      Breathing discomfort due to increased breathing resistance is known to be a
      problem with the use of N95 respirators but there is a lack of scientific data to
      quantify this effect. The purpose of this study was to assess objectively the
      impact of wearing N95 face masks on breathing resistance. A total of 14 normal
      adult volunteers (seven males and seven females) were recruited in this study.
      Nasal airflow resistance during inspiration and expiration was measured using a
      standard rhinomanometry and nasal spirometry. A modified full face mask was
      produced in-house in order to measure nasal resistance with the use of N95 (3M
      8210) respirators. The results showed a mean increment of 126 and 122% in
      inspiratory and expiratory flow resistances, respectively, with the use of N95
      respirators. There was also an average reduction of 37% in air exchange volume
      with the use of N95 respirators. This is the first reported study that
      demonstrates quantitatively and objectively the substantial impairment of nasal
      airflow in terms of increased breathing resistance with the use of N95
      respirators on actual human subjects.

PMID- 21893678
TI  - Identification of novel oxidized levuglandin D2 in marine red alga and mouse
      tissue.
AB  - In animals, the product of cyclooxygenase reacting with arachidonic acid,
      prostaglandin(PG)H(2), can undergo spontaneous rearrangement and nonenzymatic
      ring cleavage to form levuglandin(LG)E(2) and LGD(2). These LGs and their isomers
      are highly reactive gamma-ketoaldehydes that form covalent adducts with proteins,
      DNA, and phosphatidylethanolamine in cells. Here, we isolated a novel oxidized
      LGD(2) (ox-LGD(2)) from the red alga Gracilaria edulis and determined its planar
      structure. Additionally, ox-LGD(2) was identified in some tissues of mice and in
      the lysate of phorbol-12-myristate-13-acetate (PMA)-treated THP-1 cells incubated
      with arachidonic acid using LC-MS/MS. These results suggest that ox-LGD(2) is a
      common oxidized metabolite of LGD(2). In the planar structure of ox-LGD(2), H8
      and H12 of LGD(2) were dehydrogenated and the C9 aldehyde was oxidized to a
      carboxylic acid, which formed a lactone ring with the hydrated ketone at C11.
      These structural differences imply that ox-LGD(2) is less reactive with amines
      than LGs. Therefore, ox-LGD(2) might be considered a detoxification metabolite of
      LGD(2).

PMID- 21893679
TI  - 5-HT1A receptor agonists enhance pyramidal cell firing in prefrontal cortex
      through a preferential action on GABA interneurons.
AB  - 5-HT(1A) receptors (5-HT1AR) are expressed by pyramidal and gamma-aminobutyric
      acidergic (GABAergic) neurons in medial prefrontal cortex (mPFC). Endogenous
      serotonin inhibits mPFC pyramidal neurons via 5-HT1AR while 5-HT1AR agonists,
      given systemically, paradoxically excite ventral tegmental area-projecting
      pyramidal neurons. This enhances mesocortical dopamine function, a process
      involved in the superior efficacy of atypical antipsychotic drugs on negative and
      cognitive symptoms of schizophrenia. Moreover, the 5-HT1AR-induced increase of
      pyramidal discharge may also contribute to the maintenance of activity patterns
      required for working memory, impaired in schizophrenia. Given the importance of
      these processes, we examined the neurobiological basis of pyramidal activation
      through 5-HT1AR using the prototypical agent 8-OH-DPAT. (+/-)8-OH-DPAT (7.5
      MUg/kg i.v.) increased discharge rate and c-fos expression in rat mPFC pyramidal
      neurons. Local blockade of GABA(A) inputs with gabazine (SR-95531) avoided (+/-)8
      OH-DPAT-induced excitations of pyramidal neurons. Moreover, (+/-)8-OH-DPAT
      administration reduced the discharge rate of mPFC fast-spiking GABAergic
      interneurons at doses exciting pyramidal neurons. Activation of other 5-HT1AR
      subpopulations (raphe nuclei or hippocampus) does not appear to contribute to
      pyramidal excitations. Overall, the present data suggest a preferential action of
      (+/-)8-OH-DPAT on 5-HT1AR in GABAergic interneurons. This results in pyramidal
      disinhibition and subsequent downstream excitations of subcortical structures
      reciprocally connected with PFC, such as midbrain dopaminergic neurons.

PMID- 21893680
TI  - White-matter connectivity between face-responsive regions in the human brain.
AB  - Face recognition is of major social importance and involves highly selective
      brain regions thought to be organized in a distributed functional network.
      However, the exact architecture of interconnections between these regions remains
      unknown. We used functional magnetic resonance imaging to identify face
      responsive regions in 22 participants and then employed diffusion tensor imaging
      with probabilistic tractography to establish the white-matter pathways between
      these functionally defined regions. We identified strong white-matter connections
      between the occipital face area (OFA) and fusiform face area (FFA), with a
      significant right-hemisphere predominance. We found no evidence for direct
      anatomical connections between FFA and superior temporal sulcus (STS) or between
      OFA and STS, contrary to predictions based on current cognitive models. Instead,
      our findings point to segregated processing along a ventral extrastriate visual
      pathway to OFA-FFA and another more dorsal system connected to STS and
      frontoparietal areas. In addition, early occipital areas were found to have
      direct connections to the amygdala, which might underlie a rapid recruitment of
      limbic brain areas by visual inputs bypassing more elaborate extrastriate
      cortical processing. These results unveil the structural neural architecture of
      the human face recognition system and provide new insights on how distributed
      face-responsive areas may work together.

PMID- 21893681
TI  - Is the link between anatomical structure and function equally strong at all
      cognitive levels of processing?
AB  - Whereas low-level sensory processes can be linked to macroanatomy with great
      confidence, the degree to which high-level cognitive processes map onto anatomy
      is less clear. If function respects anatomy, more accurate intersubject
      anatomical registration should result in better functional alignment. Here, we
      use auditory functional magnetic resonance imaging and compare the effectiveness
      of affine and nonlinear registration methods for aligning anatomy and functional
      activation across subjects. Anatomical alignment was measured using normalized
      cross-correlation within functionally defined regions of interest. Functional
      overlap was assessed using t-statistics from the group analyses and the degree to
      which group statistics predict high and consistent signal change in individual
      data sets. In regions related to early stages of auditory processing, nonlinear
      registration resulted in more accurate anatomical registration and stronger
      functional overlap among subjects compared with affine. In frontal and temporal
      areas reflecting high-level processing of linguistic meaning, nonlinear
      registration also improved the accuracy of anatomical registration. However,
      functional overlap across subjects was not enhanced in these regions. Therefore,
      functional organization, relative to anatomy, is more variable in the frontal and
      temporal areas supporting meaning-based processes than in areas devoted to
      sensory/perceptual auditory processing. This demonstrates for the first time that
      functional variability increases systematically between regions supporting lower
      and higher cognitive processes.

PMID- 21893682
TI  - Lateralized auditory cortical alpha band activity and interregional connectivity
      pattern reflect anticipation of target sounds.
AB  - The anticipation of stimuli facilitates the top-down preparation of neuronal
      tissue involved in the processing of forthcoming targets. Increasing evidence in
      the visual modality emphasizes the anticipatory adjustment of visual cortex
      excitability through modulations of oscillatory alpha power. In the auditory
      system, however, this relationship has not yet been established. Furthermore, the
      association between anticipatory modulations of auditory alpha power and a
      potential top-down network within these anticipatory preparation processes
      remains unexplained. To disclose these processes, we recorded
      magnetoencephalography while visually cuing participants to attend to either ear
      and to anticipate forthcoming auditory stimuli. For the cue-stimulus phase, we
      expected an asymmetric modulation of auditory alpha power when attending to the
      left or right ear, assuming that frontoparietal regions would phase synchronize
      with the auditory cortex in an asymmetric pattern. Beamformer source solutions
      demonstrate an asymmetric modulation of auditory alpha power following visual
      cues expressed in a strong right auditory alpha power increase when attending to
      the right ear. Furthermore, the right auditory cortex is functionally connected
      to the frontal eye fields during the ipsilateral alpha increase. Altogether,
      these results contribute significantly to the understanding of how auditory
      anticipation acts on a local as well as on a network level.

PMID- 21893683
TI  - Functional connectivity between anatomically unconnected areas is shaped by
      collective network-level effects in the macaque cortex.
AB  - Coherent spontaneous blood oxygen level-dependent (BOLD) fluctuations have been
      intensely investigated as a measure of functional connectivity (FC) in the
      primate neocortex. BOLD-FC is commonly assumed to be constrained by the
      underlying anatomical connectivity (AC); however, cortical area pairs with no
      direct AC can also have strong BOLD-FC. On the mechanism generating FC in the
      absence of direct AC, there are 2 possibilities: 1) FC is determined by signal
      flows via short connection patterns, such as serial relays and common afferents
      mediated by a third area; 2) FC is shaped by collective effects governed by
      network properties of the cortex. In this study, we conducted functional magnetic
      resonance imaging in anesthetized macaque monkeys and found that BOLD-FC between
      unconnected areas depends less on serial relays through a third area than on
      common afferents and, unexpectedly, common efferents, which does not match the
      first possibility. By utilizing a computational model for interareal BOLD-FC
      network, we show that the empirically detected AC-FC relationships reflect the
      configuration of network building blocks (motifs) in the cortical anatomical
      network, which supports the second possibility. Our findings indicate that FC is
      not determined solely by interareal short connection patterns but instead is
      substantially influenced by the network-level cortical architecture.

PMID- 21893684
TI  - Contextual factors influencing readiness for dissemination of obesity prevention
      programs and policies.
AB  - Within the realm of obesity prevention research, there have been many promising
      interventions to improve physical activity and nutrition among diverse target
      populations. However, very little information is known about the dissemination
      and replication of these interventions. In 2007 and 2008 as part of a larger
      obesity prevention initiative, Missouri Foundation for Health funded 19 community
      based programs throughout the state that showed promise of being model practices
      and committed to promoting their dissemination. Semi-structured key informant
      interviews were conducted with 64 individuals across the grant sites to help
      stage their readiness for dissemination. Through these interviews, the project
      team was able to identify the variables that impact a program's readiness for
      widespread distribution. Some factors contributing to readiness include: strong
      intervention planning and an existing sustainability plan; physical space
      available for the intervention; staff and monetary resources; administrative buy
      in; community buy-in and engagement; a strong partner base and an agency with a
      healthy and active mission. These findings add to the literature by
      systematically identifying a set of key contextual variables. The qualitative
      data collected support a proposed framework and helps to establish a process for
      maintaining successful interventions based on several important factors that
      impact dissemination.

PMID- 21893685
TI  - Potential effectiveness of specific anti-smoking mass media advertisements among
      Australian Indigenous smokers.
AB  - Aboriginal and Torres Strait Islander Australians (Indigenous Australians) have
      more than twice the smoking prevalence of non-Indigenous Australians. Anti
      smoking campaigns have demonstrated success in the general population but little
      is known about their impact among Indigenous people. A total of 143 Indigenous
      and a comparison group of 156 non-Indigenous smokers from South Australia were
      shown 10 anti-smoking advertisements representing a range of advertisements
      typically aired in Australia. Participants rated advertisements on a five-point
      Likert scale assessing factors including message acceptance and personalized
      effectiveness. On average, Indigenous people rated the mainstream advertisements
      higher than non-Indigenous people and were more likely to report that they
      provided new information. Advertisements with strong graphic imagery depicting
      the health effects of smoking were rated highest by Indigenous smokers.
      Advertisements featuring real people describing the serious health consequences
      of smoking received mixed responses. Those featuring an ill person were rated
      higher by Indigenous people than those featuring the family of the person
      affected by a smoking-related disease. With limited Indigenous-specific messages
      available and given the finite resources of most public health campaigns,
      exposure to mainstream strong graphic and emotive first-person narratives about
      the health effects of smoking are likely to be highly motivating for Indigenous
      smokers.

PMID- 21893686
TI  - The photoperiod, circadian regulation and chronodisruption: the requisite
      interplay between the suprachiasmatic nuclei and the pineal and gut melatonin.
AB  - The current scientific literature is replete with investigations providing
      information on the molecular mechanisms governing the regulation of circadian
      rhythms by neurons in the suprachiasmatic nucleus (SCN), the master circadian
      generator. Virtually every function in an organism changes in a highly regular
      manner during every 24-hour period. These rhythms are believed to be a
      consequence of the SCN, via neural and humoral means, regulating the intrinsic
      clocks that perhaps all cells in organisms possess. These rhythms optimize the
      functions of cells and thereby prevent or lower the incidence of pathologies.
      Since these cyclic events are essential for improved cellular physiology, it is
      imperative that the SCN provide the peripheral cellular oscillators with the
      appropriate time cues. Inasmuch as the 24-hour light:dark cycle is a primary
      input to the central circadian clock, it is obvious that disturbances in the
      photoperiodic environment, e.g., light exposure at night, would cause disruption
      in the function of the SCN which would then pass this inappropriate information
      to cells in the periphery. One circadian rhythm that transfers time of day
      information to the organism is the melatonin cycle which is always at low levels
      in the blood during the day and at high levels during darkness. With light
      exposure at night the amount of melatonin produced is compromised and this
      important rhythm is disturbed. Another important source of melatonin is the
      gastrointestinal tract (GIT) that also influences the circulating melatonin is
      the generation of this hormone by the entero-endocrine (EE) cells in the gut
      following ingestion of tryptophan-containing meal. The consequences of the
      altered melatonin cycle with the chronodisruption as well as the alterations of
      GIT melatonin that have been linked to a variety of pathologies, including those
      of the gastrointestinal tract.

PMID- 21893687
TI  - Cardiovascular effects of the combination of levosimendan and valsartan in
      hypertensive Dahl/Rapp rats.
AB  - Hypertension is the main risk factor for left ventricular hypertrophy and
      development of diastolic heart failure. There is no yet treatment, which can
      effectively reduce mortality in patients suffering from heart failure with
      preserved systolic function. We tested whether the calcium sensitizer
      levosimendan and the AT1-receptor antagonist valsartan could protect from salt
      induced hypertension, cardiovascular mortality and heart failure in Dahl/Rapp
      salt-sensitive rats fed for 7 weeks with a high salt diet (8% NaCl). Levosimendan
      (1 mg/kg/day via drinking water) and valsartan (30 mg/kg in the food)
      monotherapies and their combination prevented mortality in Dahl/Rapp rats. The
      drug combination evoked an additive effect on blood pressure, cardiac
      hypertrophy, cardiomyocyte cross-sectional area, target organ damage and
      myocardial ANP mRNA expression. There was a close correlation between systolic
      blood pressure and cardiac hypertrophy, cardiac and renal damage. As compared to
      Dahl/Rapp controls kept on low-salt diet (NaCl 0.3%). The high salt rats
      exhibited impaired diastolic relaxation as assessed by isovolumic relaxation
      time. Levosimendan alone and in combination with valsartan, improved diastolic
      relaxation without significantly improving systolic function. Our findings are
      evidence for an additive effect between levosimendan and valsartan on blood
      pressure and a blood pressure-dependent protection against the development of
      salt-induced target organ damage. The present study also demonstrates that
      levosimendan, alone or in combination with valsartan, can correct diastolic
      dysfunction induced by salt-dependent hypertension.

PMID- 21893688
TI  - CellfoodTM improves respiratory metabolism of endothelial cells and inhibits
      hypoxia-induced reactive oxygen species (ros) generation.
AB  - Endothelial mitochondria, the major site of ATP generation, modulate the
      intracellular dynamics of reactive oxygen species (ROS), which, in turn, control
      endothelial function. Adequate oxygen (O(2)) supply is required by endothelial
      cells (EC). Both hypoxia and hyperoxia may favor the overproduction of ROS
      leading to oxidative stress, mitochondrial damage and endothelial dysfunction. We
      investigated the capability and mechanisms of CellfoodTM (CF), an antioxidant
      compound, to modulate O(2) availability and mitochondrial respiratory metabolism
      and to regulate ROS generated by hypoxia in EC in vitro. Human umbilical vein
      endothelial cells (HUVEC) and ECV-304 were evaluated for the O(2) consumption
      using a Clark's electrode. The O(2) consumption rate rose, during the first
      minutes after CF addition and was associated with increase in mitochondrial
      oxidative capacity and good cell viability. Similar behaviours were observed when
      EC were exposed to CF for up to 8 days. The O(2) consumption increased and was
      accompanied by both intracellular rise of ATP and maintainment of LDH
      concentration. Hypoxia-induced ROS generation was significantly inhibited by CF,
      through the up-regulated expression of MnSOD, an anti-oxidant responsible for
      mitochondrial function preservation. The EC hypoxic response is mediated by the
      hypoxia master regulator HIF-1alpha whose activation was attenuated by CF, in
      concomitance with MnSOD up-regulation. Our results suggest a role for CF in
      improoving respiratory metabolism and in activating anti-oxidant mechanisms in
      EC, thus preserving endothelial function.

PMID- 21893689
TI  - Long-term effect of prazosin administration on blood pressure, heart and
      structure of coronary artery of young spontaneously hypertensive rats.
AB  - The sympathetic nervous system belongs to the essential systems participating in
      blood pressure (BP) regulation. Inhibitory intervention into the key point of its
      operation (alfa 1 adrenoceptors) in the prehypertensive period of spontaneously
      hypertensive rats (SHR) might affect the development of the hypertension in later
      ontogenic periods. We studied the long-term effect of prazosin administration on
      the cardiovascular system of young Wistar rats and SHR. Four-week-old animals
      were used: Wistar rats, SHR, and Wistar rats and SHR receiving prazosin (10
      mg/kg/day in tap water) by gavage. Blood pressure (BP) was measured weekly by the
      plethysmographic method. After six weeks under anaesthesia, the carotid artery
      was cannulated for BP registration, and the jugular vein was cannulated for
      administration of drugs. Afterwards, the animals were perfused with a
      glutaraldehyde fixative at a pressure of 120 mmHg. The septal branch of the left
      descending coronary artery was processed using electron microscopy. The prazosin
      administration evoked the following results in both groups: a decrease of BP and
      heart/body weight ratio, enhancement of hypotensive responses to acetylcholine
      (0.1 MUg, 1 MUg, and 10 MUg), and an increase in the inner diameter of the
      coronary artery without changes in wall thickness, cross sectional area (CSA)
      (tunica intima+media), CSA of smooth muscle cells, and extracellular matrix. In
      the SHR group, a reduction was observed in BP increase after noradrenaline (1
      MUg) application. CSA of endothelial cells which was decreased in the SHR
      (compared to the control Wistar rats) was increased after prazosin treatment (up
      to control value). Long-term prazosin administration from early ontogeny
      partially prevented some pathological alterations in the cardiovascular system of
      SHR.

PMID- 21893690
TI  - Effect of phoshpodiesterase 4 (PDE4) inhibibtors on eotaxin expression in humen
      bronchial epithelial cells.
AB  - The increasing number of eosinophils into bronchoaelvolar space is observed
      during noninfectious inflammatory lung diseases. Eotaxins (eotaxin-1/CCL11,
      eotaxin-2/CCL24, eotaxin-3/CCL26) are the strongest chemotactic agents for
      eosinophils. Inhibitors of phosphodiesterase 4 (PDE4), the enzyme decomposing
      cAMP, are anti-inflammatory agents which act through cAMP elevation and inhibit
      numerous steps of allergic inflammation. The effect of PDE4 inhibitors on eotaxin
      expression is not known in details. The aim of our study was to evaluate the
      influence of PDE4 inhibitors: rolipram and RO-20-1724 on expression of eotaxins
      in bronchial epithelial cell line BEAS-2B. Cells were preincubated with PDE4
      inhibitors or dexamethasone for 1 hour and then stimulated with IL-4 or IL-13
      alone or in combination with TNF-alpha. After 48 hours eotaxin protein level was
      measured by ELISA and mRNA level by real time PCR. RESULTS: PDE4 inhibitors
      decreased CCL11 and CCL26 expression only in cultures co-stimulated with TNF
      alpha. In cultures stimulated with IL-4 and TNF-alpha rolipram and RO-20-1724
      diminished CCL11 mRNA expression by 34 and 37%, respectively, and CCL26 by 43 and
      47%. In cultures stimulated with IL-13 and TNF-alpha rolipram and RO-20-1724
      decreased expression of both eotaxins by about 50%. These results were confirmed
      at the protein level. The effect of PDE4 inhibitors on eotaxin expression in BEAS
      2B cells, in our experimental conditions, depends on TNF-alpha contribution.

PMID- 21893691
TI  - Defining the blood plasma protein repertoire of seven day old dairy calves - a
      preliminary study.
AB  - During the early postnatal period in calves various adaptational changes occur.
      These functional, morphological and also metabolic alteration are reflected by
      blood plasma protein changes as they are secreted and shed from many cells and
      tissues. Blood plasma protein pattern of an adult cattle differs in some respect
      when compared with neonatal calves. There exist a very few data concerning 2-D
      maps of neonatal calves blood plasma. The above prompted us to establish protein
      pattern of this biological fluid characteristic of healthy, 7 day old, Polish
      Black-and-White (Polish Friesian) breed calves. Blood plasma proteins of the
      isoelectric point ranging from 4.0 to 7.0 were analyzed by the aid of high
      resolution two-dimensional electrophoresis (2-DE). Subsequently, 79 excised
      protein spots corresponding to 23 different gene products were identified using
      matrix-assisted laser desorption/ionisation mass spectrometer (MALDI-TOF MS).
      Protein map obtained in the present study may be useful in assessing the changes
      in the calves blood plasma protein profiles occurring in response to different
      physiological and/or pathophysiological factors.

PMID- 21893692
TI  - Effect of partial and complete blockade of vanilloid (TRPV1-6) and ankyrin
      (TRPA1) transient receptor potential ion channels on urinary bladder motor
      activity in an experimental hyperosmolar overactive bladder rat model.
AB  - The study investigated the mechanisms through which the hyperosmolarity might
      induce detrusor overactivity (DO). We compared the bladder activity in response
      to partial and complete blockade of TRPV1-6 and TRPA1 receptors. Experiments were
      performed on 42 rats. DO was induced by using hyperosmolar saline. All animals
      were randomly divided into six groups. The measurements represent the average of
      five bladder micturition cycles. Hyperosmolar saline induced DO. The complete
      blockade of TRPV1-6 and TRPA1 prevented DO. The partial blockade of TRPV1 didn't
      prevented DO. In the voiding phase periodical bladder contractions complexes
      occurred leading to slow urine flow due to bladder distension. Ruthenium red and
      capsaicin resulted in complete disorganisation of detrusor muscle contractility
      impairing urine voiding and leading to constantly lasting urine retention in
      healthy rats. CONCLUSIONS: hyperosmolar-induced DO is mediated by TRPV and TRPA1
      channels; the hyperosmolar stimuli of urinary bladder might be transmitted mostly
      via ruthenium red sensitivity pathway.

PMID- 21893693
TI  - Evaluation of melatonin effectiveness in the adjuvant treatment of ulcerative
      colitis.
AB  - Ulcerative colitis (UC) is a chronic disease characterized by the variable
      clinical picture with the inflammatory changes which can involve the whole colon
      or its distal part. The current treatments for UC are mostly nonspecific, not
      always effective, and often accompanied by serious side effects. Therefore, there
      is a considerable interest in finding alternative and more tolerable treatments
      for this serious disease. Several lines of experimental studies have shown that
      melatonin (MEL) regulates the extensive gut immune system and exerts
      antiinflammatory and immunomodulatory effects suggesting its beneficial action in
      UC by reducing and controlling inflammation. The study aimed at evaluating the
      effect of MEL on the activity of inflammatory process and sustaining the
      remission in patients with UC. It comprised 60 patients with left-sided UC,
      divided in two equal groups of 30 patients each (38 women and 22 men, aged 26-49
      years), similar in both groups, who were in clinical remission for the last 12
      months. Patients, during a next period of 12 months, were given mesalazine in
      daily doses 2 x 1.0 g and melatonin 5 mg daily at bedtime (group I) or placebo
      (group II). All the patients on MEL adjuvant treatment remained in remission
      during 12 months of observation with The Mayo Clinic Disease Activity Index
      (MCDAI) values 1.50+/-0.51 at the beginning and 2.75+/-1.86 points after 12
      months. In the placebo group significantly higher MCDAI values were observed than
      in patients on MEL after 6, 9 and 12 months. At the inclusion MCDAI was 1.61+/
      0.68 points and at the end of observation it reached the value of 5.10+/-2.22
      points. In MEL group CRP level remained within the normal range during the course
      of the study (from 3.49+/-1.40 to 4.17+/-2.10 mg/dl). Whereas in the placebo
      group from the end of the third month the steady rise in CRP blood concentration
      was noted from 3.85+/-1.29 to 13.13+/-6.08 mg/dl. Parallelly to CRP rise a
      significant decrease in hemoglobin concentration in blood from 12.05+/-0.69 to
      10.93+/-0.81 g/dl was observed in patients receiving placebo and the values
      significantly differed between the groups after 3 (p<0.05), 6, 9 and 12 months
      (p<0.01). The level of anxiety and the intensity of depression in patients on
      adjuvant MEL decreased during the study but there were no statistical differences
      noted between the groups. The results of the study allowed drawing the conclusion
      that adjuvant melatonin therapy may help in sustaining remission in patients with
      UC.

PMID- 21893694
TI  - Serum gastrin and gastric enterochromaffin-like cells during estrous cycle,
      pregnancy and lactation, and in response to estrogen-like agents in rats.
AB  - Histamine-containing enterochromaffin-like (ECL) cells are numerous in the
      gastric mucosa. They operate under the control of gastrin. ECL-cell tumors
      (gastric carcinoids) may arise as a consequence of sustained hypergastrinemia.
      For reasons unknown, such tumors have a female preponderance both in laboratory
      animals and humans. The present study consisted of four experiments exploring the
      possibility that gender-related factors might affect rat ECL cells. 1) A gender
      difference in terms of serum gastrin concentration and oxyntic mucosal histidine
      decarboxylase (HDC) activity appeared in Sprague-Dawley but not Wistar rats.
      Ultrastructural appearance of the ECL cells did not differ between genders. 2)
      During the different phases of the estrous cycle, the serum gastrin
      concentration, HDC activity and histamine concentration did not change. 3) During
      pregnancy, the serum gastrin concentration was suppressed, while it was increased
      during lactation. The HDC activity and the histamine concentration of the oxyntic
      mucosa were correlated with the levels of circulating gastrin. 4) Twelve-month
      treatment with estrogen-like agents, dieldrin and/or toxaphene (alone or in
      combination) was without any effect on the ECL cells neither in male nor in
      female rats. In conclusion, the ECL cells are under the control of gastrin, but
      probably not hormones that involve in the estrous cycle and pregnancy and
      lactation in rats. Possible gender-related factors behind the female
      preponderance of ECL-cell tumors remain unknown.

PMID- 21893695
TI  - On the benefit of whey-cultured Lactobacillus casei in murine colitis.
AB  - The objective of this study was to examine the prophylactic and therapeutic
      effect of whey-cultured Lactobacillus casei (L. casei) in a murine model of
      colitis. Colitis was induced by intracolonic administration of a mixture of 2,4,6
      trinitrobenzenesulphonic acid (TNBS)/absolute ethanol in male Wistar rats.
      Animals were divided into 5 groups including sham (normal group), control
      (vehicle-treated), positive control (dexamethasone 1 mg/kg/day, orally),
      prevention (10(8) cfu L. casei/day, orally, 14 days before induction of colitis),
      and treatment (10(8) cfu L. casei/day, orally, 14 days after induction of
      colitis). After 14-days treatment, the animals were sacrificed on the day 15.
      Distal colons were removed for examining histological and biochemical assays.
      Biomarkers including TNF-alpha, myeloperoxidase (MPO), and lipid peroxidation
      (LPO) were measured in the homogenate of colon. Results indicated an apparent
      improvement in colon histopathology scores, TNF-alpha, MPO, and LPO in the
      treatment group, whereas prevention group did not demonstrate positive efficacy
      in prevention of colonic damage. It is concluded that L. casei grown in whey
      culture is very effective in ameliorating both biochemical and histopathological
      markers of colitis if used post induction of colitis but not if used before
      induction of colitis. The difference between effects of L. casei when used pre
      colitis and post-colitis confirms its mechanism of action as an anti toxic stress
      agent. Further studies should be made in IBD patients.

PMID- 21893696
TI  - Effects of peroxisome proliferator-activated receptors-gamma ligands on dextran
      sodium sulphate-induced colitis in rats.
AB  - Recent studies indicate the involvement of peroxisone proliferator-activated
      receptor-gamma (PPAR-gamma) in the inflammatory reaction. The exact mechanism of
      PPAR-gamma action has not been elucidated. It is supposed that PPAR-gamma
      regulates transcription of genes responsible for encoding cytokines involved in
      the inflammatory response. The latest studies, carried out to explain the
      pathogenesis of non-specific colitis, confirm beneficial effects of PPAR-gamma
      agonists on attenuation of colon inflammation. The aim of the present study was
      to assess the effects of nuclear PPAR-gamma activity on the course of
      experimental acute colitis induced by intragastric administration of dextran
      sodium sulphate (DSS) using the PPAR-gamma agonist rosiglitazone and the
      antagonist BADGE in rats. Colitis in Wistar rats was induced by 1.5% DSS
      administered in drinking water for 8 days. Animals with induced colitis received
      rosiglitazone, bisphenol A diglycidyl ether (BADGE) or both substances. After
      decapitation, colons were macroscopically and histopathologically evaluated.
      Levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), interleukin-10 (IL
      10), tumor necrosis factor-alpha (TNF-alpha) and myeloperoxidase (MPO) were
      determined in serum and colon homogenates using ELISA. In rats with
      experimentally induced colitis receiving rosiglitazone, the inflammatory reaction
      was found to be markedly limited; ulceration, oedema and infiltration activity
      were reduced. The activated PPAR-gamma inhibit the expression of proinflammatory
      factors, such as IL-6, TNF-alpha, and neutrophil chemotaxis, which was evidenced
      by MPO reduction in serum and colon homogenates mediated by rosiglitazone. The
      positive effects of rosiglitazone on expression of IL-10 were also demonstrated.
      During the short period of observation, BADGE did not increase histopathological
      inflammatory markers.

PMID- 21893697
TI  - Antibiotic treatment with ampicillin accelerates the healing of colonic damage
      impaired by aspirin and coxib in the experimental colitis. Importance of
      intestinal bacteria, colonic microcirculation and proinflammatory cytokines.
AB  - Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for their anti
      inflammatory, analgesic and antipyretic effects, however their use is associated
      with the broad spectrum of side effects observed in human as well as the
      experimental animals. Despite damaging activity of NSAIDs in upper
      gastrointestinal (GI) tract, these drugs exert deleterious influence in lower GI
      tract, including colon. The role of GI microflora in the pathogenesis of NSAIDs
      induced experimental colonic damage is not completely understood. The aim of this
      study was 1) to evaluate the relative importance of the GI microflora on the
      experimental colonic damage in the presence of caused by NSAID, and 2) to assess
      the efficacy of antibiotic treatment with ampicillin on the process of healing of
      colitis. We compared the effect of vehicle, ASA applied 40 mg/kg intragastrically
      (i.g.) or the selective cyclooxygenase (COX)-2 inhibitor, celecoxib (25 mg/kg
      i.g.) without or with ampicillin treatment (800 mg/kg i.g.) administered
      throughout the period of 10 days, on the intensity of TNBS-induced colitis in
      rats. The severity of colonic damage, the alterations in the colonic blood flow
      (CBF) and myeloperoxidase (MPO) activity, the mucosal expression of TNF-alpha, IL
      1beta, COX-2, VEGF and iNOS and the plasma concentration of TNF-alpha and IL
      1beta were assessed. In all rats, the faeces samples as well as those from the
      colonic mucosa, blood, liver and spleen underwent microbiological evaluation for
      intestinal bacterial species including Escherichia coli and Enterococcus spp. The
      administration of TNBS resulted in macroscopic and microscopic lesions
      accompanied by the significant fall in the CBF, an increase in tissue weight and
      4-5-fold rise in the MPO activity and a significant increase in the plasma IL
      1beta and TNF-alpha levels. ASA or celecoxib significantly increased the area of
      colonic lesions, enhanced MPO activity and caused the marked increase in colonic
      tissue weight and plasma IL-1beta and TNF-alpha levels, as well as an
      overexpression of mRNA for IL-1beta and TNF-alpha, COX-2, VEGF and iNOS in the
      colonic tissue. ASA and coxib also resulted also in a significant increase of E.
      coli counts in the stool at day 3 and day 10 day of the observation compared with
      the intact rats. Moreover, E. coli translocation from the colon to the blood and
      extraintestinal organs such as liver and spleen in the group of rats treated
      without or with ASA and coxib. E. coli was the most common bacteria isolated from
      these organs. Treatment with ampicillin significantly attenuated the ASA- or
      celecoxib-induced increase in plasma levels of IL-1beta and TNF-alpha and
      suppressed the mucosal mRNA expression for IL-1beta and TNF-beta, COX-2, iNOS and
      VEGF in the colonic mucosa. Ampicillin administration caused a significant fall
      in the number of E. coli in the faeces at day 3 and day 10 of observation in ASA-
      and coxib-treated rats with colitis. Antibiotic therapy markedly reduced
      bacterial translocation to the colonic tissue and the extraintestinal organs such
      as the liver and spleen. We conclude that administration of ASA and to lesser
      extent of celecoxib, delays the healing of experimental colitis and enhances the
      alterations in colonic blood flow, proinflammatory markers such as IL-1beta, TNF
      alpha, COX-2, iNOS and VEGF and increased intestinal mucosal permeability
      resulting in the intestinal bacterial translocation to the blood, spleen and
      liver. Antibiotic treatment with ampicillin is effective in the diminishing of
      the severity of colonic damage, counteracts both the NSAID-induced fall in
      colonic microcirculation and bacterial E.coli translocation to the
      extraintestinal organs.

PMID- 21893698
TI  - The common adiponutrin variant p.I148M does not confer gallstone risk but affects
      fasting glucose and triglyceride levels.
AB  - Recently the common adiponutrin (PNPLA3) polymorphism p.I148M has been identified
      as a genetic determinant of severe forms of non-alcoholic fatty liver disease and
      alcoholic liver disease. Additionally, insulin resistance - linked to the
      development of non-alcoholic steatohepatitis - increases the risk of developing
      gallstones. Here we assessed whether the PNPLA3 p.I148M (c.444 C-G) polymorphism
      affects glucose and lipid levels and increases gallstone risk. We analysed 229
      individuals with gallstones from 108 families (age 24-80 years, BMI 17-55
      kg/m(2)) and 258 gallstone-free controls (age 20-70 years, BMI 14-43 kg/m(2)).
      Fasting glucose, triglyceride and cholesterol serum levels were determined. The
      p.I148M polymorphism was genotyped using a PCR-based assay with 5'-nuclease and
      fluorescence detection. Case-control association tests and nonparametric linkage
      (NPL) analysis in sib-pairs were performed. Individuals carrying the [GG]
      genotype had significantly (P<0.0001) higher median fasting glucose levels as
      compared to [GC] and [CC] carriers. After adjustment for multiple testing, we
      detected a trend for an association between triglyceride levels and variant
      adiponutrin in gallstone patients (P=0.032), and gallstone cases carrying the
      genotype [CC] presented with significantly higher triglyceride levels than the
      corresponding controls (P<0.003). No significant effects on cholesterol
      metabolism were detected. Neither genotype distributions nor NPL scores provided
      evidence for association or linkage between the PNPLA3 variant and gallstones. In
      conclusion, homozygous carriers of the PNPLA3 risk allele display higher fasting
      glucose. Although this adiponutrin variant may affect triglyceride homeostasis,
      it does not increase the risk of cholelithiasis.

PMID- 21893699
TI  - Effect of maternal tobacco smoking or exposure to second-hand smoke on the levels
      of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine of mother and
      the first urine of newborn.
AB  - Tobacco smoking during pregnancy is associated with a variety of negative
      consequences not only for the mother, but also for the developing fetus. Many
      studies have shown that carcinogens contained in tobacco smoke permeate across
      the placenta, and are found in fetus. The aim of the study was to determine the
      prenatal exposure to tobacco-specific carcinogenic N-nitrosamines on the basis of
      measurements of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in urine of
      smoking and second-hand smoke (SHS) exposed women and in the first urine of their
      newborns. A questionnaire documenting demographics and socio-economical data,
      smoking habits and exposure to SHS was completed by 121 delivering women near or
      at term. Maternal concentrations of cotinine and NNAL were measured in urine of
      the mother and the first urine of her newborn infant by liquid chromatography
      tandem mass spectrometry (LC/MS/MS). The mean concentration of cotinine was 439.2
      ng/mg creatinine and NNAL concentration in urine of smoking women was 74.0 pg/mg
      creatinine, and for her newborn 78.6 pg/mg creatinine. Among mothers exposed to
      SHS, cotinine and NNAL mean concentration were 23.1 ng/mg creatinine, and 26.4
      pg/mg creatinine. In newborns of SHS exposed mothers during pregnancy the mean
      concentration of NNAL was 34.1 pg/mg creatinine, respectively. Active tobacco
      smoking as well as passive exposure to smoking during pregnancy is an important
      source of tobacco specific N-nitrosamines to the fetuses as evidenced by
      increased concentrations of this carcinogen. Determination of NNAL in maternal
      urine samples can be a useful biomarker of prenatal exposure of newborn to
      carcinogenic nitrosamines.

PMID- 21893700
TI  - Chemopreventive effects of Calluna vulgaris and Vitis vinifera extracts on UVB
      induced skin damage in SKH-1 hairless mice.
AB  - Solar ultraviolet radiation (UV) is a major cause of non-melanoma skin cancer in
      humans. Photochemoprevention with natural products represents a simple but very
      effective strategy in the management of cutaneous neoplasia. The study
      investigated the protective activity of Calluna vulgaris (Cv) and red grape seeds
      (Vitis vinifera L, Burgund Mare variety) (BM) extracts in vivo on UVB-induced
      deleterious effects in SKH-1 mice skin. Forty SKH-1 mice were randomly divided
      into 4 groups (n=10): control, UVB irradiated, Cv + UVB irradiated, BM+UVB
      irradiated. Both extracts were applied topically on the skin in a dose of 4 mg/40
      MUl/cm(2) before UVB exposure - single dose. The effects were evaluated in skin
      24 hours after irradiation through the presence of cyclobutane pyrimidine dimers
      (CPDs) and sunburn cells, tumor necrosis factor-alpha (TNF-alpha), interleukin
      (IL)-6 levels. The antioxidant activity of BM extract was higher than those of Cv
      extract as determined using stable free radical DPPH assay and ABTS test. One
      single dose of UVB generated formation of CPDs (p<0.0001) and sunburn cells
      (p<0.0002) and increased the cytokine levels in skin (p<0.0001). Twenty hours
      following irradiation BM extract inhibited UVB-induced sunburn cells (p<0.02) and
      CPDs formation (p<0.0001). Pretreatment with Cv and BM extracts resulted in
      significantly reduced levels of IL-6 and TNF-alpha compared with UVB alone
      (p<0.0001). Our results suggest that BM extracts might be a potential candidate
      in preventing the damages induced by UV in skin.

PMID- 21893701
TI  - Bio-Search Computing: integration and global ranking of bioinformatics search
      results.
AB  - In the Life Sciences, numerous questions can be addressed only by comprehensively
      searching different types of data that are inherently ordered, or are associated
      with ranked confidence values. We previously proposed Search Computing to support
      the integration of the results of search engines with other data and
      computational resources. This paper presents how well known bioinformatics
      resources can be described as search services in the search computing framework
      and integrated analyses over such services can be carried out. An initial set of
      bioinformatics services has been described and registered in the search computing
      framework and a bioinformatics search computing (Bio-SeCo) application using
      these services has been created. This current prototype application, the
      available services that it uses, the queries that are supported, the kind of
      interaction that is therefore made available to the users, and the future
      scenarios are here described and discussed.

PMID- 21893702
TI  - Magnetic biodegradable Fe3O4/CS/PVA nanofibrous membranes for bone regeneration.
AB  - In recent years, interest in magnetic biomimetic scaffolds for tissue engineering
      has increased considerably. The aim of this study is to develop magnetic
      biodegradable fibrous materials with potential use in bone regeneration. Magnetic
      biodegradable Fe(3)O(4)/chitosan (CS)/poly vinyl alcohol (PVA) nanofibrous
      membranes were achieved by electrospinning with average fiber diameters ranging
      from 230 to 380 nm and porosity of 83.9-85.1%. The influences of polymer
      concentration, applied voltage and Fe(3)O(4) nanoparticles loading on the
      fabrication of nanofibers were investigated. The polymer concentration of 4.5
      wt%, applied voltage of 20 kV and Fe(3)O(4) nanoparticles loading of lower than 5
      wt% could produce homogeneous, smooth and continuous Fe(3)O(4)/CS/PVA nanofibrous
      membranes. X-ray diffraction (XRD) data confirmed that the crystalline structure
      of the Fe(3)O(4), CS and PVA were maintained during electrospinning process.
      Fourier transform infrared spectroscopy (FT-IR) demonstrated that the Fe(3)O(4)
      loading up to 5 wt% did not change the functional groups of CS/PVA greatly.
      Transmission electron microscopy (TEM) showed islets of Fe(3)O(4) nanoparticles
      evenly distributed in the fibers. Weak ferrimagnetic behaviors of membranes were
      revealed by vibrating sample magnetometer (VSM) test. Tensile test exhibited
      Young's modulus of membranes that were gradually enhanced with the increase of
      Fe(3)O(4) nanoparticles loading, while ultimate tensile stress and ultimate
      strain were slightly reduced by Fe(3)O(4) nanoparticles loading of 5%.
      Additionally, MG63 human osteoblast-like cells were seeded on the magnetic
      nanofibrous membranes to evaluate their bone biocompatibility. Cell growth
      dynamics according to MTT assay and scanning electron microscopy (SEM)
      observation exhibited good cell adhesion and proliferation, suggesting that this
      magnetic biodegradable Fe(3)O(4)/CS/PVA nanofibrous membranes can be one of
      promising biomaterials for facilitation of osteogenesis.

PMID- 21893703
TI  - A unified approach for social-medical discovery.
AB  - In this paper we describe a novel social-medical discovery solution, based on an
      idea of social and medical data unification. Built on foundations of exploratory
      search technologies, the proposed discovery solution is better tailored for the
      social-medical discovery task. We then describe its implementation within the IBM
      Medics system and discuss a sample usecase which demonstrates several new social
      medical discovery opportunities.

PMID- 21893704
TI  - Information provision for adolescents with cancer.
AB  - Recent research has provided a detailed insight into what information cancer
      patients as a generic group require and we now understand that this requirement
      changes during the disease episode. This paper will focus on the information
      needs of adolescent cancer patients as little research has been done in this area
      and unlike every other group of cancer patients very little improvement in
      information provision and clinical outcomes for this small but important group of
      people has occurred over the past 20 years. Adolescents have specialised needs
      and have for too long been grouped either with young children or adults. This
      paper describes our current knowledge regarding their special needs and outlines
      future directions to facilitate equality in information provision for this group.

PMID- 21893705
TI  - Electronic symptom reporting by patients: a literature review.
AB  - A literature review has been conducted to gain an overview of which technologies
      and patient groups have previously been employed in scientific studies with
      regard to patients reporting symptoms electronically. This paper presents
      preliminary results from the review, based on the abstracts from relevant
      publications. The Medline database search identified 974 publications. Of these,
      235 (24%) met the inclusion/exclusion criteria. The number of studies has
      increased heavily over the past two decades. A lot of the studies are small with
      regard to sample size, but we see that the number of studies increase over time.
      Cancer and lung diseases are the largest diagnosis groups. Cancer symptom
      reporting seems to take place inside the healthcare institutions, while lung
      disease and musculoskeletal disease reporting mainly take place at home via
      Internet.

PMID- 21893706
TI  - Increasing physical activity through health-enabling technologies: the project
      "being strong without violence".
AB  - Due to the increasing prevalence of adiposity in children numerous schools are
      introducing prevention programmes. Among these is "Gewaltlos Starksein" ("Being
      strong without violence"), a project of Hauptschule Sophienstrabetae
      Braunschweig, Germany (a general education secondary school for grades 5-10).
      This study aims to discover possible increases in activity through "Gewaltlos
      Starksein" where health-enabling technologies play a major role. A prospective
      intervention study with a span of 1.5 years was designed to measure this increase
      in activity. Partners in this study were Hauptschule Sophienstrabetae as the
      intervention group and Grund- und Hauptschule Pestalozzistrabetae as control
      group. Data collection was performed using a multi-sensor device, and
      questionnaires. Confirmatory data analysis of average metabolic equivalent (METs)
      yielded no significant results. Exploratory analysis showed interesting results,
      especially concerning the number of steps during leisure time. Descriptive
      analysis of questionnaires showed that all children enjoy physical activity.
      There were differences in sports team participation, open-air games and club
      affiliation. The study could not prove that the intervention "Gewaltlos
      Starksein" improves physical activity in children. However, the increased leisure
      activity step count indicates that "Gewaltlos Starksein" has positive effects on
      children's behaviour. This should be investigated in a further study in
      cooperation with psychologists.

PMID- 21893707
TI  - Review of mobile terminal-based tools for diabetes diet management.
AB  - Changing dietary habits is one of the most challenging tasks of diabetes self
      management. Mobile terminals are increasingly used as platforms for tools to
      support diet management and health promotion. We present literature describing
      mobile terminal-based support tools for management of diabetes focused on diet.
      We also propose a summary of key success factors for designing such tools and
      discuss recommendations for future research.

PMID- 21893708
TI  - Interaction between COPD patients and healthcare professionals in a cross-sector
      tele-rehabilitation programme.
AB  - This paper explores how technology affects the interaction between chronic
      obstructive pulmonary disease (COPD) patients and healthcare professionals in a
      cross-sector tele-rehabilitation programme. The qualitative analysis has shown
      that a community of rehabilitation can be created despite the presence of long
      distance technology. In the tele-rehabilitation programme, the interaction
      between the COPD patients at home and the healthcare professionals at the clinic
      has evolved with dialogue as the basis for mutual learning processes and new
      relationships. Managed properly, rehabilitation at a distance can be both
      effective and satisfying.

PMID- 21893709
TI  - Enhancing self-efficacy for self-management in people with cystic fibrosis.
AB  - This paper reports on a research trial designed to evaluate the benefits of a
      health mentoring programme supported with a web and mobile phone based self
      monitoring application for enhancing self-efficacy for self-management skills and
      quality of life for people with CF. This randomised, single-blind controlled
      trial evaluated two strategies designed to improve self-management behaviour and
      quality of life. Task-specific self-efficacy was fostered through mentorship and
      self-monitoring via a mobile phone application. Trial participants were
      randomised into one of three groups: Control, Mentor-only and Mentor plus mobile
      phone. Analysis and discussion focus on the experiences of participants through a
      methodology utilising descriptive statistics and semi-structured interviews. The
      results highlight the challenges of stimulating self-management behaviours
      particularly in adolescents and in the evaluation of the role of mobile
      applications in supporting them.

PMID- 21893710
TI  - Evaluation of a Hyperlinked Consumer Health Dictionary for reading EHR notes.
AB  - In this paper, we report on a pilot study conducted to test the usefulness and
      understandability of definitions in a Consumer Health Dictionary (IVS-CHD). Our
      two main goals for this study were to evaluate functionality of the dictionary
      when embedded in electronic health records (EHR) and determine the methodology
      for our larger-scale project to iteratively develop the IVS-CHD. The hyperlinked
      IVS-CHD was made available to thoracic surgery patients reading their own EHR. We
      asked patients to rate definitions on two 5-level Likert items measuring
      perceived usefulness and understandability. We also captured the terms that
      patients wanted defined, but that were not included in the IVS-CHD. Preliminary
      results indicate the types of problems that must be avoided when creating
      definitions, for example, that patients prefer detailed explanations that include
      medical outcomes, and that do not use "unfamiliar" terms they must also look up.
      We also have gained insight into the types of terms that patients want defined
      from their EHR notes, especially certain abbreviations. Patients further
      commented on the experience of reading EHR notes directly from the same system
      used by healthcare personnel and the help strategy of linking the contents to a
      hyperlinked dictionary.

PMID- 21893711
TI  - A pilot assessment of why patients choose not to participate in self-monitoring
      oral anticoagulant therapy.
AB  - Patients suffering from heart diseases often face lifelong oral anticoagulant
      therapy. Traditionally, the patient's general practitioner takes care of the
      treatment. An alternative management scheme is a self-monitoring setup where the
      patient monitors and manages the oral treatment himself. Despite international
      evidence of reduced thrombosis risk and death rate among patients enrolled in
      self-monitoring, a majority of eligible patients deselect this opportunity.
      Little is about the causes if this. This study is a pilot assessment of why
      patients, located in the North Denmark Region, choose not to participate. The
      study is based on qualitative interviews with two nurses working in a medical
      practice and two patients participating in conventional anticoagulant therapy.
      The results of this study seem to suggest that at least some patients feel a lack
      of information to base their decision regarding self-monitoring or conventional
      management on and that the knowledge among the health personnel at the medical
      clinics should be increased.

PMID- 21893712
TI  - Mobile peer support in diabetes.
AB  - As in other domains, there has been unprecedented growth in diabetesrelated
      social media in the past decade. Although there is not yet enough evidence for
      the clinical benefits of patient-to-patient dialogue using emergent social media,
      patient empowerment through easier access to information has been proven to
      foster healthy lifestyles, and to delay or even prevent progression of secondary
      illnesses. In the design of diabetes-related social media, we need access to
      personal health data for modelling the core disease-related characteristics of
      the user. We discuss design aspects of mobile peer support, including acquisition
      of personal health data, and design artefacts for a healthcare recommender
      system. We also explore mentoring models as a tool for managing the transient
      relationships among peers with diabetes. Intermediate results suggest acquiring
      health data for modelling patients' health status is feasible for implementing a
      personalized and mobile peer-support system.

PMID- 21893713
TI  - Evolution of health web certification through the HONcode experience.
AB  - Today, the Web is a media with increasing pervasiveness around the world. Its use
      is constantly growing and the medical field is no exception. With this large
      amount of information, the problem is no longer about finding information but
      assessing the credibility of the publishers as well as the relevance and accuracy
      of the documents retrieved from the web. This problem is particularly relevant in
      the medical area which has a direct impact on the well-being of citizens and in
      the Web 2.0 context where information publishing is easier than ever. To address
      the quality of the medical Internet, the HONcode certification proposed by the
      Health On the Net Foundation (HON) is certainly the most successful initiative.
      The aims of this paper are to present certification activity through the HONcode
      experience and to show that certification is more complex than a simple code of
      conduct. Therefore, we first present the HONcode, its application and its current
      evolutions. Following that, we give some quantitative results and describe how
      the final user can access the certified information.

PMID- 21893714
TI  - Personal health data: patient consent in information age.
AB  - In this paper we report on findings related to treatment of patient consent in
      various circumstances and geographic domains; explore transfer of health data
      between custodians and geo-political entities; and emphasize importance of
      educating general public about issues related to handling health data. A specific
      set of questions about consent/legislation and related issues in the Canada, the
      USA and the EU are addressed in an attempt to answer them systematically. This
      comparison identifies similarities and differences along a set of dimensions.

PMID- 21893715
TI  - Emotions and personal health information management: some implications for
      design.
AB  - This work reflects on the translation of a paper-based information system into an
      electronic one, taking account of the emotional dimension of material artifacts.
      A qualitative analysis carried out through semi-structured interviews enabled us
      to describe laypeople's healthcare practices, and specifically the use of
      "pediatric booklets", which are paper health diaries designed to provide parents
      with a repository of the most relevant clinical data about their children. Our
      analysis reveals that parents' use of the booklet does not depend only on the
      clinical relevance of the information contained in it. Its success rather depends
      on practices that reshape the booklet's original meaning. In particular, parents
      use booklets as containers for other clinical records, and they consider them
      more as objects of affection and symbols of their caring for their children than
      as clinical tools with instrumental value in themselves. In the discussion we
      consider the risks of dematerializing health information tools by underestimating
      the relevance of the emotional side.

PMID- 21893716
TI  - Socio-technical challenges in designing a web-based communication platform.
AB  - This paper takes a socio-technical perspective to analyze the ongoing practices
      of making an eHealth infrastructure, namely a web-based communication platform,
      which aims to improve healthcare delivery in Norway. The platform is planned to
      support interaction between patients and healthcare providers, patient access to
      personal health information, and dissemination of health knowledge to the public.
      The analysis is based on the 'scales of infrastructure' concept found in
      Information Systems research, which shows the complexity of the design,
      development and implementation process across three scales of activities for
      achieving durability: institutionalization, organizing work, and technology
      enactment. The case analysis brings the non-linearity of the ongoing practices to
      the foreground, enabling a more in-depth understanding of the relationship
      between technology design and infrastructural work.

PMID- 21893717
TI  - Results of the 10 HON survey on health and medical internet use.
AB  - The Internet is increasingly being used as a means to search and communicate
      health information. As the mission of Health on the Net Foundation (HON) is to
      guide healthcare consumers and professionals to trustworthy online information,
      we have been interested in seeing the trend of the attitudes towards Internet use
      for health purposes since 1996. This article presents the results of the
      10<sup>th</sup> HON survey conducted in July-August 2010 (in English and French).
      It was hosted on the HON site with links from Facebook and Twitter and from
      HONcode certified web sites. There were 524 participants coming mainly from
      France (28%), the UK (18%) and the USA (18%). 65% of participants represented the
      "general public", while the remaining 35% were professionals. Information quality
      remains the main barrier users encounter while looking for health information
      online; at the same time, 79% believe they critically assess online content. Both
      patients and physicians consider the Internet to be helpful in facilitating their
      communication during consultations, although professionals are more sceptic than
      the general public. These results justify the continuing efforts of HON to raise
      public awareness regarding online health information and the ethical, quality and
      transparency issues, and to educate and guide users towards trustworthy health
      information.

PMID- 21893718
TI  - Social connectedness through ICT and the influence on wellbeing: the case of the
      CareRabbit.
AB  - The CareRabbit has been introduced as a technological innovation in the care for
      children, enabling family and friends to stay in touch while the child is
      hospitalized. This study addresses influence of this innovation on the wellbeing
      of the children, and uses the validated KINDL questionnaire, eliciting
      information from children and parents at the end of hospitalization. A baseline
      and an experimental measurement are compared. The children in the CareRabbit
      group scored slightly higher on the KINDL questionnaire than children in the
      control group. For young children (age 4-7) the difference was large. Initial
      findings indicate that CareRabbit has a positive influence on wellbeing, although
      sample size and measured differences limit the support for this conclusion. The
      measured difference suggests that CareRabbit may be more valuable for younger
      children.

PMID- 21893719
TI  - Technological choices for mobile clinical applications.
AB  - The rise of cheaper and more powerful mobile devices make them a new and
      attractive platform for clinical applications. The interaction paradigm and
      portability of the device facilitates bedside human-machine interactions. The
      better accessibility to information and decision-support anywhere in the hospital
      improves the efficiency and the safety of care processes. In this study, we
      attempt to find out what are the most appropriate Operating System (OS) and
      Software Development Kit (SDK) to support the development of clinical
      applications on mobile devices. The Android platform is a Linux-based, open
      source platform that has many advantages. Two main SDKs are available on this
      platform: the native Android and the Adobe Flex SDK. Both of them have
      interesting features, but the latter has been preferred due its portability at
      comparable performance and ease of development.

PMID- 21893720
TI  - Modified Rand method to derive quality indicators: a case study in cardiac
      rehabilitation.
AB  - Quality indicators (QIs) are increasingly used to summarize quality of care and
      to give professionals' performance feedback. We have previously developed a
      continuous multifaceted guideline implementation strategy that integrates
      computerized decision support with feedback on QIs and benchmarking. This paper
      focuses on development of QIs, and presents results of a case study in the field
      of cardiac rehabilitation. We present a modified Rand method that combines
      results from a literature search and guideline review with knowledge of an expert
      and patient panel in an extensive rating and consensus procedure. All sources
      contributed to the final set of 18 QIs for cardiac rehabilitation.

PMID- 21893721
TI  - A cloud-based semantic wiki for user training in healthcare process management.
AB  - Successful healthcare process design requires active participation of users who
      are familiar with the cooperative and collaborative nature of healthcare
      delivery, expressed in terms of healthcare processes. Hence, a reusable,
      flexible, agile and adaptable training material is needed with the objective to
      enable users instill their knowledge and expertise in healthcare process
      management and (re)configuration activities. To this end, social software, such
      as a wiki, could be used as it supports cooperation and collaboration anytime,
      anywhere and combined with semantic web technology that enables structuring
      pieces of information for easy retrieval, reuse and exchange between different
      systems and tools. In this paper a semantic wiki is presented as a means for
      developing training material for healthcare providers regarding healthcare
      process management. The semantic wiki should act as a collective online memory
      containing training material that is accessible to authorized users, thus
      enhancing the training process with collaboration and cooperation capabilities.
      It is proposed that the wiki is stored in a secure virtual private cloud that is
      accessible from anywhere, be it an excessively open environment, while meeting
      the requirements of redundancy, high performance and autoscaling.

PMID- 21893722
TI  - Reference architecture of application services for personal wellbeing information
      management.
AB  - Personal information management has been proposed as an important enabler for
      individual empowerment concerning citizens' wellbeing and health information. In
      the MyWellbeing project in Finland, a strictly citizen-driven concept of "Coper"
      and related architectural and functional guidelines have been specified. We
      present a reference architecture and a set of identified application services to
      support personal wellbeing information management. In addition, the related
      standards and developments are discussed.

PMID- 21893723
TI  - Development of a web-based decision support system for insulin self-titration.
AB  - Insulin is the most potent agent for the treatment of diabetes mellitus. However
      insulin treatment requires frequent evaluation of blood glucose levels and
      adjustment of the insulin dose. This process is called titration. To guide
      patients with type 2 diabetes using once-daily long-acting insulin, we have
      developed a web-based decision support system for insulin self-titration. The
      purpose of this paper is to provide an overview of the phases of development and
      the final design of the system. We reviewed the literature, consulted an expert
      panel, and conducted interviews with patients to elicit system requirements. This
      revealed four important aspects: the insulin titration algorithm, the handling of
      hypoglycemic events, telemedicine functionalities, and visiting frequency
      monitoring. We used these requirements to develop a fully functional system.

PMID- 21893724
TI  - TreC - a REST-based regional PHR.
AB  - The Personal Health Record (PHR) is progressively becoming a fundamental tool to
      allow people to control their health. User needs, however, impose to design a PHR
      solution that must offer a great flexibility in terms of managing heterogeneous
      health data, composing data in higher level concepts and interfacing the PHR with
      different devices to collect and visualize data. We propose to adopt REST as core
      of a regional PHR architecture and present a PHR based on this architecture
      implemented and tested in our Province.

PMID- 21893725
TI  - Next generation neonatal health informatics with Artemis.
AB  - This paper describes the deployment of a platform to enable processing of
      currently uncharted high frequency, high fidelity, synchronous data from medical
      devices. Such a platform would support the next generation of informatics
      solutions for neonatal intensive care. We present Artemis, a platform for real
      time enactment of clinical knowledge as it relates to multidimensional data
      analysis and clinical research. Through specific deployment examples at two
      different neonatal intensive care units, we demonstrate that Artemis supports: 1)
      instantiation of clinical rules; 2) multidimensional analysis; 3) distribution of
      services for critical care via cloud computing; and 4) accomplishing 1 through 3
      using current technology without a negative impact on patient care.

PMID- 21893726
TI  - Limitations in physicians' knowledge when assessing dementia diseases - an
      evaluation study of a decision-support system.
AB  - There is a need to provide tools for the medical professional at the point of
      care in the assessment of a suspected dementia disease. Early diagnosis is
      important in order to provide appropriate care so that the disease does not cause
      unnecessary suffering for the patient and relatives. DMSS (Dementia Management
      and Support System) is a clinical decision-support system that provides support
      in the diagnosis of a dementia disease, which is in use in controlled clinical
      evaluation settings in four countries. This paper reports the results of
      evaluations done in use environments in these places during a period of two
      years. Data in 218 patient cases were collected by 21 physicians during their use
      of the system in clinical practice. In 50 of the cases the use of the system were
      also observed and the physicians were interviewed in 88 cases. The collected data
      and inferences made by the system were analyzed. To summarize the results, DMSS
      gave appropriate support considering the patient case, available information and
      the user's skills and knowledge in the domain. However, the results also
      illuminated the need for extended and personalized support for the less skilled
      physician in the assessment of basic information about patients.

PMID- 21893728
TI  - An OCL-compliant GELLO Engine.
AB  - GELLO, an expression language for clinical decision support, has been approved as
      an HL7/ANSI normative standard for years. Unfortunately, there are few GELLO
      engines available in use, and the limited tooling seems to hamper a widespread
      adoption of GELLO. The objective of this paper is to validate the availability of
      implementing an OCL-compliant GELLO engine. Experimental results show that our
      GELLO engine runs successfully in a clinical guideline-based decision support
      system for chronic disease management.

PMID- 21893727
TI  - A generic system for critiquing physicians' prescriptions: usability,
      satisfaction and lessons learnt.
AB  - Clinical decision support systems have been developed to help physicians to take
      clinical guidelines into account during consultations. The ASTI critiquing module
      is one such systems; it provides the physician with automatic criticisms when a
      drug prescription does not follow the guidelines. It was initially developed for
      hypertension and type 2 diabetes, but is designed to be generic enough for
      application to all chronic diseases. We present here the results of usability and
      satisfaction evaluations for the ASTI critiquing module, obtained with GPs for a
      newly implemented guideline concerning dyslipaemia, and we discuss the lessons
      learnt and the difficulties encountered when building a generic DSS for
      critiquing physicians' prescriptions.

PMID- 21893729
TI  - Improvement of inter-services communication through a CDSS dedicated to
      myocardial perfusion scintigraphy.
AB  - This study addresses the question of communication between medical wards and the
      nuclear medicine department for the realization of myocardial perfusion
      scintigraphy. It analyses the effects of a reminder for completing the content of
      an order form. It shows that the CDSS impacted ordering practices. It could be
      seen as a system enabling to structure the information and improve the quality of
      orders.

PMID- 21893730
TI  - Prognostic data-driven clinical decision support - formulation and implications.
AB  - Existing Clinical Decision Support Systems (CDSSs) typically rely on rule-based
      algorithms and focus on tasks like guidelines adherence and drug prescribing and
      monitoring. However, the increasing dominance of Electronic Health Record
      technologies and personalized medicine suggest great potential for prognostic
      data-driven CDSS. A major goal for such systems would be to accurately predict
      the outcome of patients' candidate treatments by statistical analysis of the
      clinical data stored at a Health Care Organization. We formally define the
      concepts involved in the development of such a system, highlight an inherent
      difficulty arising from bias in treatment allocation, and propose a general
      strategy to address this difficulty. Experiments over hypertension clinical data
      demonstrate the validity of our approach.

PMID- 21893731
TI  - Knowledge-based surveillance for preventing postoperative surgical site
      infection.
AB  - At least one out of every twenty people admitted to a Canadian hospital will
      acquire an infection. These hospital-acquired infections (HAIs) take a profound
      individual and system-wide toll, resulting in thousands of deaths and hundreds of
      millions of dollars in additional expenses each year. Surveillance for HAIs is
      essential to develop and evaluate prevention and control efforts. In nearly all
      healthcare institutions, however, surveillance for HAIs is a manual process,
      requiring highly trained infection control practitioners to consult multiple
      information systems and paper charts. The amount of effort required for discovery
      and integration of relevant data from multiple sources limits the current
      effectiveness of HAIs surveillance. In this research, we apply knowledge modeling
      and semantic technologies to facilitate the integration of disparate data and
      enable automatic reasoning with these integrated data to identify events of
      clinical interest. In this paper, we focus on Surgical Site Infections (SSIs),
      which account for a relatively large fraction of all hospital acquired
      infections.

PMID- 21893732
TI  - Factors known to influence acceptance of clinical decision support systems.
AB  - Clinical Decision Support Systems (CDSS) have been shown to improve clinical
      performance and patient outcomes, but the failure rate of such systems is still
      over 50 percent. To contribute to a wider understanding of issues surrounding
      CDDS acceptance, we performed a systematic review of studies that evaluated CDSS
      implementations in clinical care to determine the factors that are associated
      with acceptance of CDSS by physicians. The factors that were found were
      categorized according to the HOT-fit framework. The mapping of factors concerning
      CDSS acceptance on the HOT-fit framework revealed gaps in each domain of the
      framework and showed that research has mainly focused on human and technology
      factors and a lack of research on organizational factors. A potential area of
      research could thus be studying the organizational factors that may influence
      CDSS acceptance.

PMID- 21893733
TI  - Cross-frontier information provision in the ALIAS European project.
AB  - The ALIAS project addresses medical services and information inadequacy to ensure
      healthcare provisions in Alpine space where telemedicine services are not widely
      exploited and linguistic barriers represent an obstacle. Alpine space touristic
      vocation makes its healthcare structures periodically inadequate to face a
      widened request of services supply. On the other hand, a major receptivity of
      those structures during the rest of the year is unnecessary due to the low
      density of local residents. ALIAS is aimed at linking together a number of
      hospitals enabling the creation of a network shaping the ALIAS Virtual Hospital
      Network for sharing medical information and adopting telemedicine services to
      improve the efficiency of hospitals in Alpine Space areas. This article focuses
      on the clinical information provision service provided in ALIAS and on the
      translation service that has been associated to it.

PMID- 21893735
TI  - Towards an interoperable information infrastructure providing decision support
      for genomic medicine.
AB  - Genetic dispositions play a major role in individual disease risk and treatment
      response. Genomic medicine, in which medical decisions are refined by genetic
      information of particular patients, is becoming increasingly important. Here we
      describe our work and future visions around the creation of a distributed
      infrastructure for pharmacogenetic data and medical decision support, based on
      industry standards such as the Web Ontology Language (OWL) and the Arden Syntax.

PMID- 21893734
TI  - Event-driven architecture for health event detection from multiple sources.
AB  - Early detection of potential health threats is crucial for taking actions in
      time. It is unclear in which information source an event is reported first and,
      information from various sources can be complementing. Thus, it is important to
      search for information in a very broad range of sources. Furthermore, real-time
      processing is necessary to deal with the huge amounts of incoming data in time.
      Event-driven architectures are designed to address such challenges. This will be
      shown in this paper by presenting the architecture of a public health
      surveillance system that follows this style. Starting from concrete user
      requirements and scenarios, we introduce the architecture with its components for
      content collection, data analysis and integration. The system will allow for the
      monitoring of events in real-time as well as retrospectively.

PMID- 21893736
TI  - Identifying patients for clinical trials using fuzzy ternary logic expressions on
      HL7 messages.
AB  - Identifying eligible patients is one of the most critical parts of any clinical
      trial. The process of recruiting patients for the third phase of any clinical
      trial is usually done manually, informing relevant physicians or putting notes on
      bulletin boards. While most necessary information is already available in
      electronic hospital information systems, required data still has to be looked up
      individually. Most university hospitals make use of a dedicated communication
      server to distribute information from independent information systems, e.g.
      laboratory information systems, electronic health records, surgery planning
      systems. Thus, a theoretical model is developed to formally describe inclusion
      and exclusion criteria for each clinical trial using a fuzzy ternary logic
      expression. These expressions will then be used to process HL7 messages from a
      communication server in order to identify eligible patients.

PMID- 21893737
TI  - Towards a metadata registry for evaluating augmented medical interventions.
AB  - Quality evaluation in the field of Augmented Surgery is strategic for public
      health policies. It implies to be able to effectively perform evaluation of
      Quality in term of Expected Medical Benefit (EMB). The notion of EMB is complex
      and not standardized in this field. To define and to evaluate EMB, it is
      necessary to discover the knowledge on the domain targeted by the device and to
      structure it. This paper presents first parts of this work. Focused on navigated
      knee surgery, it led us to obtain two main results: the identification of a new
      criterion for evaluating EMB obtained thanks to the formalization of a new kind
      of metadata. These encouraging results seem to offer new perspectives for the
      evaluation of devices from the field of augmented surgery.

PMID- 21893738
TI  - A comparison of internal versus external risk-adjustment for monitoring clinical
      outcomes.
AB  - Internal and external prognostic models can be used to calculate severity of
      illness adjusted mortality risks. However, it is unclear what the consequences
      are of using an external model instead of an internal model when monitoring an
      institution's clinical performance. Theoretically, using an internal prognostic
      model is preferred while external models are often more widely available. In this
      simulation study we explored the difference between the use of internal and
      external models on the degree and types of warning signals given by RA-EWMA
      control charts in the detection of increasing mortality in the ICU. Increases in
      mortality were correctly detected in 60% of cases (after 24 months) with the
      internal model, regardless of prior ICU performance. When using the external risk
      adjustment model, such increases were only detected for the average and poor
      performing ICUs. When the mortality rate was held constant, using the external
      model resulted in many incorrect warning signals. We conclude that the use of
      internal risk-adjustment models is preferable for monitoring clinical
      performance.

PMID- 21893739
TI  - Interoperability driven integration of biomedical data sources.
AB  - In this paper, we introduce a data integration methodology that promotes
      technical, syntactic and semantic interoperability for operational healthcare
      data sources. ETL processes provide access to different operational databases at
      the technical level. Furthermore, data instances have they syntax aligned
      according to biomedical terminologies using natural language processing. Finally,
      semantic web technologies are used to ensure common meaning and to provide
      ubiquitous access to the data. The system's performance and solvability
      assessments were carried out using clinical questions against seven healthcare
      institutions distributed across Europe. The architecture managed to provide
      interoperability within the limited heterogeneous grid of hospitals. Preliminary
      scalability result tests are provided.

PMID- 21893740
TI  - Creating knowledge archive in the internet medical consultant for decision
      support at the point of care.
AB  - The Internet Medical Consultant - IMC is a knowledge sharing system for
      physicians. The system's main purpose is to collect and store the communication
      between its users and to provide easy retrieval of stored information. The system
      provides access to human generated knowledge at the point of care. Having that
      kind of knowledge at hand can be very helpful for physicians when they make
      decisions. This paper describes the process of knowledge capturing, creating and
      searching the knowledge archive, for final utilisation of that knowledge at point
      of care.

PMID- 21893741
TI  - Architecture of a decision support system to improve clinicians' interpretation
      of abnormal liver function tests.
AB  - The objective of this work was to create a self-working computerized clinical
      decision support system (CDSS) able to analyze liver function tests (LFTs) in
      order to provide diagnostic suggestions and helpful care support to clinicians.
      We developed an expert system that processes exclusively para-clinical
      information to provide diagnostic propositions. Drugs are a major issue in
      dealing with abnormal LFTs, therefore we created a drug-disease causality
      assessment tool to include drugs in the differential diagnosis. Along with the
      results, the CDSS will guide clinicians in the care process offering them case
      specific support in the form of guidelines, order sets and references to recent
      articles. The CDSS will be implemented in Geneva University Hospitals clinical
      information system (CIS) during year 2011. For the time being, preliminary tests
      have been conducted on case reports chosen randomly on Pubmed. Considered as
      medical challenges, case reports were nevertheless processed correctly by the
      program to the extent that 18 cases out of 20 were diagnosed accurately.

PMID- 21893742
TI  - Push and pull models to manage patient consent and licensing of multimedia
      resources in digital repositories for case-based reasoning.
AB  - Patient consents for distribution of multimedia constitute a significant element
      of medical case-based repositories in medicine. A technical challenge is posed by
      the right of patients to withdraw permission to disseminate their images or
      videos. A technical mechanism for spreading information about changes in
      multimedia usage licenses is sought. The authors gained their experience by
      developing and managing a large (>340 cases) repository of virtual patients
      within the European project eViP. The solution for dissemination of license
      status should reuse and extend existing metadata standards in medical education.
      Two methods: PUSH and PULL are described differing in the moment of update and
      the division of responsibilities between parties in the learning object exchange
      process. The authors recommend usage of the PUSH scenario because it is better
      adapted to legal requirements in many countries. It needs to be stressed that the
      solution is based on mutual trust of the exchange partners and therefore is most
      appropriate for use in educational alliances and consortia. It is hoped that the
      proposed models for exchanging consents and licensing information will become a
      crucial part of the technical frameworks for building case-based repositories.

PMID- 21893743
TI  - Next steps in evaluation and evidence - from generic to context-related.
AB  - INTRODUCTION: E-health systems are increasingly important and widespread, but
      their selection and implementation are still frequently based on belief, rather
      than scientific evidence, and adverse effects are not systematically addressed.
      Progress is being made in promoting generic evaluation methodologies as a source
      of scientific evidence, but effort is now needed to consider methods for special
      situations. METHOD: Review of five evaluation contexts - national e-health plans,
      telemedicine, Health Informatics 3.0, usability and economics. CONCLUSION:
      Identification of requirements for approaches to be developed in these five
      settings.

PMID- 21893744
TI  - Virtual ward round.
AB  - "Virtual Ward Round" is a web-based blended learning tool. The program simulates
      hospital ward rounds. Within a virtual environment, students make diagnosis and
      order treatments. Tutors prepare cases easily to ensure realistic cases directly
      linked to the corresponding classes. The program "Virtual Ward Round" will
      hopefully be enrichment to the curriculum-based teaching.

PMID- 21893745
TI  - Professional development of health informatics in Northern Ireland.
AB  - This paper addresses the assessment and verification of health informatics
      professional competencies. Postgraduate provision in Health Informatics was
      targeted at informatics professionals working full-time in the National Health
      Service, in Northern Ireland, United Kingdom. Many informatics health service
      positions do not require a formal informatics background, and as we strive for
      professionalism, a recognized qualification provides important underpinning. The
      course, delivered from a computing perspective, builds upon work-based
      achievement and provides insight into emerging technologies associated with the
      'connected health' paradigm. The curriculum was designed with collaboration from
      the Northern Ireland Health and Social Care ICT Training Group. Material was
      delivered by blended learning using a virtual learning environment and face-to
      face sessions. Professional accreditation was of high importance. The aim was to
      provide concurrent qualifications: a postgraduate certificate, awarded by the
      University of Ulster and a professional certificate validated and accredited by a
      professional body comprising experienced health informatics professionals.
      Providing both qualifications puts significant demands upon part-time students,
      and a balance must be achieved for successful completion.

PMID- 21893746
TI  - How important is theory in health informatics? A survey of UK academics.
AB  - The disciplinary status of health informatics remains unclear. Is it an art or a
      science? Does it have a body of theory? A survey was devised for UK academics
      that teach or research health informatics. Forty-six responses were received,
      twenty-five from the target group (representing between a quarter and a third of
      the population of interest). Health informatics is not perceived to have a well
      known and clearly definable body of theory, but there is a clear demand for a
      more theoretical basis for the discipline. Journals and conferences were rated as
      the best sources of theory and seven key textbooks were identified.

PMID- 21893747
TI  - Better quality in healthcare through gamified simulation based skill training
      application.
AB  - Although the screening of abdominal aortic diameter helps to identify men with
      abdominal aortic aneurysm and saves lives, there is need to coordinate and
      synchronize screening personnel's way to work. This article describes the design
      of a game based skill training application that could give the screening
      personnel an additional opportunity to refine measuring of abdominal aortic
      diameter in ultrasound images. The design work follows the steps of the Goal
      Directed design process. Consequently, the design activities are divided into six
      phases: the Research, Modelling, Requirements Definition, Framework Definition,
      Refinement and Development support. The design process described in this paper
      finishes with usability testing of an interactive prototype. The evaluation of
      the design was conducted with end users by studying their subjective ratings and
      performance on given tasks. The overall results of the usability testing show
      that the interactive prototype of the skill training application is not yet fully
      usable. Consequently, further improvement of the interface design is needed. The
      identified usability issues and collected qualitative and quantitative material
      about the interaction between test participants and the interface can guide the
      next design iteration and lead to more usable design.

PMID- 21893748
TI  - Implementation of a web-based interactive virtual patient case simulation as a
      training and assessment tool for medical students.
AB  - OBJECTIVE: Structured Clinical Examinations (OSCE) are resource intensive, not
      practical as teaching tools, and their reliability depends on evaluators.
      Computer-based case simulations ("virtual patients", VP) have been advocated as
      useful and reliable tools for teaching clinical skills and evaluating competence.
      We have developed an internet-based VP system designed both for practice and
      assessment of medical students. The system uses interactive dialogue with natural
      language processing, and is designed for history taking, evaluation of physical
      examination, including recognition of visual findings and heart and lung sounds,
      and ordering lab-and imaging tests. The system includes a practice modality that
      provides feedback, and a computerized OSCE. The reliability of our system was
      assessed over the last three years by comparing the clinical competence of
      medical students in similar VP and human OSCE. A total of 262 students were
      evaluated with both exam modalities. The correlation between the two exams scores
      was highly significant (p<0.001). Alpha Cronbach for the computerized exam was
      0.82-0.89 in the 3 years, and was substantially higher than that of the
      conventional OSCE each year. We conclude that a computerized VP OSCE is a
      reliable examination tool, with the advantage of providing also a training
      modality.

PMID- 21893749
TI  - Online CME usage patterns.
AB  - The paper reports the findings of the analysis of a sample of 829 online
      Continuous Medical Education (CME) enrolments aimed at inspecting users'
      preferences and behaviours. The contents of the analyzed course are provided as
      online SCORM (Sharable Content Object Reference Model) resources together with
      the corresponding Pdf downloadable versions allowing different usage patterns
      (online only, Pdf only, online AND Pdf, mixed online OR Pdf). The results point
      out that there is not a specific preference for one of the four patterns and that
      most of the users access both navigable modules and Pdf documents. Demographic
      characteristics and initial knowledge level do not influence the choice of a
      specific usage pattern that probably depends on internal or context factors. From
      the point of view of knowledge acquisition, the four patterns are equivalent. As
      regards users' behaviour, the analysis has pointed out two issues: 1) the
      attitude to conclude the course in a short time and to reach good test scores,
      but not the excellence; 2) learning activity tracing data were not available for
      all the enrolments. Cues for discussion are proposed.

PMID- 21893750
TI  - How do nursing students perceive the notion of EHR? an empirical investigation.
AB  - This paper describes an empirical study aiming to assess nursing students'
      perceptions on Electronic Health Record (EHR) concepts and their potential future
      attitude towards use. Based on the theoretical ground of Rogers' Innovation
      Diffusion Theory and other research works, a formulated model was empirically
      validated among ninety nursing undergraduates. Data analysis was based on partial
      least squares path modeling. Results highlighted the very strong significant
      effect of relative advantage and observability as well as the significant effect
      of perceived ease of use to attitude towards using EHR systems. The study
      findings are discussed along with limitations and future work in the current
      field.

PMID- 21893751
TI  - Recording and podcasting of lectures for students of medical school.
AB  - Information and communication technology (ICT) becomes an important way for the
      knowledge transmission, especially in the field of medicine. Podcasting (mobile
      broadcast content) has recently emerged as an efficient tool for distributing
      information towards professionals, especially for e-learning contents.The goal of
      this work is to implement software and hardware tools for collecting medical
      lectures at its source by direct recording (halls and classrooms) and provide the
      automatic delivery of these resources for students on different type of devices
      (computer, smartphone or videogames console). We describe the overall
      architecture and the methods used by medical students to master this technology
      in their daily activities. We highlight the benefits and the limits of the
      Podcast technologies for medical education.

PMID- 21893752
TI  - Developing an electronic health record for intractable diseases in Japan.
AB  - Because intractable diseases result from unidentifiable causes and are very
      difficult to treat, they require a lifelong epidemiology database. Japan does not
      use global unique identifiers, such as social security numbers, so we conducted a
      feasibility study regarding an electronic health record (EHR). An EHR can be used
      as a lifelong database and reduce conventional administrative work. However, it
      will be necessary to develop additional tools to overcome issues specific to
      Japan before an EHR can be implemented.

PMID- 21893753
TI  - Three key concerns for a successful EPR deployment and usage.
AB  - The health care environment is unique because of the large and complex
      organisation with a traditional hierarchic structure that is governed by laws and
      regulations. This paper examines how a large Swedish health care organisation
      work with usability issues regarding Electronic Patient Record (EPR) deployment
      and usage. EPR systems have great impact on work environment and clinical work
      routines will not be performed in the same way as before. This paper analyse how
      the EPR management and core business understand their EPR responsibilities and
      work with usability aspects at different levels in the organisations. The paper
      reveals that there is a conflict about responsibility between EPR management and
      core business management. The reasons for the confusion are contradictive
      understanding of what an EPR system is, an IT system or a tool for the core
      business to perform better health care work. This leads to that care staff's
      experience regarding the EPR system's usability, is not being listened to within
      the organisation. Three key concerns for a successful EPR deployment and usage
      are identified and further analysed; education, evaluation and support &
      improvement ideas.

PMID- 21893754
TI  - Implementation of an open source provider organization registry service.
AB  - Healthcare Information Exchange Networks (HIEN) enables the exchange of medical
      information between different institutions. One of the biggest problems running a
      HIEN is the unique identification of the care providers. The provider and
      organisation registry service (PORS) has to provide a unique identifier for care
      providers. The concept and the implementation of PORS will be described in this
      article. Finally the PORS implementation will be compared with the Integrating
      the Healthcare Enterprise (IHE) profile for a Healthcare Provider Directory
      (HPD).

PMID- 21893755
TI  - Implementation and experimentation of TEDIS: an information system dedicated to
      patients with pervasive developmental disorders.
AB  - This article aims at describing the implementation and experimentation of TEDIS,
      an information system dedicated to patients with Pervasive Developmental
      Disorder. The experiment included 30 prospective patient records aged from 3.2 to
      7.5 with an average of 6.3. Preliminary patient data analysis highlighted the
      need of improving the data collection process, by making relevant data
      systematically and accurately documented. Despite a small study ample size, data
      analysis also showed the interest of such information system in making evident
      improvements in patient care and resources allocation after medical and clinical
      expert assessment.

PMID- 21893756
TI  - Traceability of patient records usage: barriers and opportunities for improving
      user interface design and data management.
AB  - Although IT governance practices (like ITIL, which recommends on the use of audit
      logs for proper service level management) are being introduced in many Hospitals
      to cope with increasing levels of information quality and safety requirements,
      the standard maturity levels of hospital IT departments is still not enough to
      reach the level of frequent use of audit logs. This paper aims to address the
      issues related to the existence of AT in patient records, describe the Hospitals
      scenario and to produce recommendations. Representatives from four hospitals were
      interviewed regarding the use of AT in their Hospital IS. Very few AT are known
      to exist in these hospitals (average of 1 per hospital in an estimate of 21
      existing IS). CIOs should to be much more concerned with the existence and
      maintenance of AT. Recommendations include server clock synchronization and using
      advanced log visualization tools.

PMID- 21893757
TI  - Important ingredients for health adaptive information systems.
AB  - Healthcare information systems frequently do not truly meet clinician needs, due
      to the complexity, variability, and rapid change in medical contexts. Recently
      the internet world has been transformed by approaches commonly termed 'Web 2.0'.
      This paper proposes a Web 2.0 model for a healthcare adaptive architecture. The
      vision includes creating modular, user-composable systems which aim to make all
      necessary information from multiple internal and external sources available via a
      platform, for the user to use, arrange, recombine, author, and share at will,
      using rich interfaces where advisable. Clinicians can create a set of 'widgets'
      and 'views' which can transform data, reflect their domain knowledge and cater to
      their needs, using simple drag and drop interfaces without the intervention of
      programmers. We have built an example system, MedWISE, embodying the user-facing
      parts of the model. This approach to HIS is expected to have several advantages,
      including greater suitability to user needs (reflecting clinician rather than
      programmer concepts and priorities), incorporation of multiple information
      sources, agile reconfiguration to meet emerging situations and new treatment
      deployment, capture of user domain expertise and tacit knowledge, efficiencies
      due to workflow and human-computer interaction improvements, and greater user
      acceptance.

PMID- 21893758
TI  - Everyday ethical dilemmas arising with electronic record use in primary care.
AB  - The introduction of electronic medical record systems (EMRs) into primary care
      settings alters work practices, introduces new challenges, and new roles. In the
      process of integrating an EMR into a primary care setting, clinic staff faced
      ethical challenges in their everyday work practices resulting from workarounds
      undertaken to compensate for a poor fit between system design and work practices,
      issues related to system access, and governance gaps. Examples of these issues
      are presented, and implications for system design are discussed.

PMID- 21893759
TI  - The shift in workarounds upon implementation of computerized physician order
      entry.
AB  - Workarounds are working processes deviating from formal rules or intended work
      methods to smooth workflow and circumvent problems without eliminating them.
      Former research focused on workarounds in the medication use process after
      implementation of computerized physician order entry (CPOE). This study on 2
      wards of a general hospital shows that workarounds exist in both paper-based and
      electronic prescribing systems. After CPOE implementation workarounds present in
      the paper-based system had disappeared or remained existent, and new ones had
      emerged.

PMID- 21893760
TI  - Task analysis and interoperable application services for service event
      management.
AB  - In addition to the information specifications for electronic health records,
      functional and behavioral capabilities need to be agreed to achieve
      interoperability. In this paper, we present results from task analysis and
      specification of software services to support the management of service events.
      The work has been performed to support the management of the nationally shared
      EPR in Finland. The results support the specification of information sharing and
      composition in relation to healthcare workflows and activities. The specification
      of a functional reference model and software services for the management of
      service events and encounters promotes the integration of shared EHR and systems
      adaptability for migration towards interoperable electronic health records in
      healthcare networks.

PMID- 21893761
TI  - Organs transplantation - how to improve the process?
AB  - The transplant of cadaveric organs must be performed in a short period of time in
      order to achieve satisfactory results. In Hospital S. Joao (HSJ), a large
      Portuguese hospital, during 2008 and 2009, 65 and 61 respectively potential
      donors were identified, but 12 and 19 of them were not validated as such in time.
      The number of validated donors could increase if the information workflow between
      donor hospitals and coordinator offices became more efficient. The goal of this
      work is to design and implement a multi-agent software platform to assist the
      information workflow between donor hospitals and coordinator offices. Through
      several meetings with HSJ coordinator office it was characterized a set of basic
      data that would allow coordinator offices to early identify possible organs
      donors. This preliminary characterization provided the necessary grounds for the
      development of an agent based software application allowing the storage and
      management of potential donors' information and optimizing the information
      workflow. The information workflow and the current communication processes
      characterization allowed the development of a multi-agent web platform, providing
      a way to assist the information workflow, between coordinator hospitals and their
      attached hospitals network. The platform also improves direct communication
      between coordinator offices about most relevant facts. By using this tool or a
      similar one the information workflow between donor hospitals and coordinator
      offices can become more efficient, optimizing the pre-transplantation tasks and
      consequently the number of successful transplants in our country.

PMID- 21893762
TI  - A reference architecture for integrated EHR in Colombia.
AB  - The implementation of national EHR infrastructures has to start by a detailed
      definition of the overall structure and behavior of the EHR system (system
      architecture). Architectures have to be open, scalable, flexible, user accepted
      and user friendly, trustworthy, based on standards including terminologies and
      ontologies. The GCM provides an architectural framework created with the purpose
      of analyzing any kind of system, including EHR system's architectures. The
      objective of this paper is to propose a reference architecture for the
      implementation of an integrated EHR in Colombia, based on the current state of
      system's architectural models, and EHR standards. The proposed EHR architecture
      defines a set of services (elements) and their interfaces, to support the
      exchange of clinical documents, offering an open, scalable, flexible and
      semantically interoperable infrastructure. The architecture was tested in a pilot
      tele-consultation project in Colombia, where dental EHR are exchanged.

PMID- 21893763
TI  - Integration services to enable regional shared electronic health records.
AB  - eHealth is expected to integrate a comprehensive set of patient data sources into
      a coherent continuum, but implementations vary and Portugal is still lacking on
      electronic patient data sharing. In this work, we present a clinical information
      hub to aggregate multi-institution patient data and bridge the information silos.
      This integration platform enables a coherent object model, services-oriented
      applications development and a trust framework. It has been instantiated in the
      Rede Telematica de Saude (www.RTSaude.org) to support a regional Electronic
      Health Record approach, fed dynamically from production systems at eight partner
      institutions, providing access to more than 11,000,000 care episodes, relating to
      over 350,000 citizens. The network has obtained the necessary clearance from the
      Portuguese data protection agency.

PMID- 21893764
TI  - Towards smart environments using smart objects.
AB  - Barcodes, RFID, WLAN, Bluetooth and many more technologies are used in hospitals.
      They are the technological bases for different applications such as patient
      monitoring, asset management and facility management. However, most of these
      applications exist side by side with hardly any integration and even
      interoperability is not guaranteed. Introducing the concept of smart objects
      inspired by the Internet of Things can improve the situation by separating the
      capabilities and functions of an object from the implementing technology such as
      RFID or WLAN. By aligning technological and business developments smart objects
      have the power to transform a hospital from an agglomeration of technologies into
      a smart environment.

PMID- 21893766
TI  - Building the technical infrastructure to support a study on drug safety in a
      general hospital.
AB  - We describe reorganization steps and the required technical infrastructure to
      support a multidisciplinary research project aimed at improving the safety of
      drug therapy in an emergency department (ED) of a community hospital. Assessment
      of drug safety required consolidation of data from various sources in a single
      source approach. We solved this by transferring digital data from the hospital
      information system (HIS) and attached clinical systems into a pseudonymized study
      database (secuTrial), which is also used as a web based data capturing tool to
      rate drug associated risk situations, extended by a technical extension for
      dynamic upload of further data. Paper-based documentation in the ED was digitized
      using a digital pen technology.

PMID- 21893765
TI  - Interoperability in hospital information systems: a return-on-investment study
      comparing CPOE with and without laboratory integration.
AB  - Despite its many advantages, using a computerized patient record is still
      considered as a time consuming activity for care providers. In numerous
      situations, time is wasted because of the lack of interoperability between
      systems. In this study, we aim to assess the time gains that nursing teams could
      achieve with a tightly integrated computerized order entry system. Using a time
      motion method, we compared expected versus effective time spent managing
      laboratory orders for two different computerized systems: one integrated, the
      other not integrated. Our results tend to show that nurses will complete their
      task an average of five times faster than their expected performance (p<0.001).
      We also showed that a tightly integrated system provides a threefold speed gain
      for nurses compared to a non-integrated CPOE with the laboratory information
      system (p<0.001). We evaluated the economic benefit of this gain, therefore
      arguing for a strong interoperability of systems, in addition to patient safety
      benefits.

PMID- 21893767
TI  - Implementing change in a diverse and politicized landscape.
AB  - Based on the experiences from an ongoing IT implementation project, this paper
      illustrates the complexity of large scale projects through the concept of
      diversity. The analysis shows how, no matter how mature the project becomes at
      coping with local diversity, it is still vulnerable to contextual diversity;
      especially when this is politicized. The paper concludes by pointing to the
      special responsibilities this puts on higher level decision makers.

PMID- 21893768
TI  - Characteristics of German hospitals adopting health IT systems - results from an
      empirical study.
AB  - Hospital characteristics that facilitate IT adoption have been described by the
      literature extensively, however with controversial results. The aim of this study
      therefore is to draw a set of the most important variables from previous studies
      and include them in a combined analysis for testing their contribution as single
      factors and their interactions. Total number of IT systems installed and number
      of clinical IT systems in the hospital were used as criterion variables. Data
      from a national survey of German hospitals served as basis. Based on a stepwise
      multiple regression analysis four variables were identified to significantly
      explain the degree of IT adoption (60% explained variance): 1) hospital size, 2)
      IT department, 3) reference customer and 4) ownership (private vs. public). Our
      results replicate previous findings with regard to hospital size and ownership.
      In addition our study emphasizes the importance of a reliable internal structure
      for IT projects (existence of an IT department) and the culture of testing and
      installing most recent IT products (being a reference customer). None of the
      interactions between factors was significant.

PMID- 21893769
TI  - Nursing information system: a relevant substitute of the paper nursing record.
AB  - OBJECTIVE: A teaching hospital in the Netherlands has developed a Nursing
      Information System (NIS). After the NIS was implemented in six wards in March
      2009, the NIS was evaluated. Since micro-relevance is a key-factor in adoption of
      Information Systems, the objective of this study is to reveal which aspects of
      the NIS are micro-relevant to nurses. METHODS: A paper questionnaire was
      distributed among all 195 nurses, who used the system. Included in the research
      were 93 (47.7%) respondents. Also six NIS-users were interviewed, using the USE
      IT-model. RESULTS: Nurses mainly used those functions of the NIS, which were
      essential for reporting or retrieving patient information. The NIS was
      appreciated for supplying unhampered access to complete, legible, structured
      patient data. CONCLUSIONS: For nurses the NIS is a good substitute for the paper
      record. The micro-relevance of other functionality than supplying information
      seems to be low.

PMID- 21893770
TI  - GP connector - a tool to enable access for general practitioners to a standards
      based personal and electronic health record in the Rhine-Neckar region.
AB  - Electronic health records (EHR) as well as personal health records (PHR) are in
      widespread use today. Since several years the University Hospital Heidelberg is
      implementing a so-called personal and electronic health record (PEHR). The joint
      approach is standards-based and includes several needed services. However a
      remained unresolved issue is how to connect general practitioners (GP) and their
      systems to the record. This work describes a tool called GP Connector that
      provides access for GPs to the PEHR within the law. GPs can profit from all
      advantages of the PEHR usage. Only adding documents to the record comfortably
      through standards-based interfaces remains still open. Thus, deep integration of
      the PEHR into primary systems is preferable anytime. Yet the continuous trend
      towards multi-institutional health network may also pave the way for standards
      based interfaces also in the field of practice management systems.

PMID- 21893771
TI  - Proposal of an end-to-end emergency medical system.
AB  - A new comprehensive emergency system has been proposed to facilitate and
      computerize all the processes involved in an emergency from the initial contact
      to the ambulance emergency system, to finding the right and nearest available
      ambulance, and through to accessing a Smart Online Electronic Health Record
      (SOEHR). The proposed system will critically assist in pre-hospital treatments,
      indentify availability of the nearest available specialized hospital and
      communicate with the Hospital Emergency Department System (HEDS) to provide early
      information about the incoming patient for preparation to receive and assist.

PMID- 21893772
TI  - The general practitioner in the Giant's web.
AB  - Most General Practitioners (GPs) in Norway use Electronic Health Record (EHR)
      systems to support their daily work processes. These systems were developed with
      basis in local needs. Electronic collaboration between the different actors has
      developed over time. Larger national projects like the ePrescription and the Core
      EHR are examples of projects that interact with the GPs EHR systems. The
      requirements from these projects need to be addressed by the vendors of the EHR
      systems. At the same time the GPs see a need for further development of their EHR
      systems to make them more suited as tools to support the daily work processes.
      This paper addresses the how GPs can influence on the design and development of
      their EHR systems in a situation with a preexisting installed base of systems and
      increasing requirements from many actors.

PMID- 21893773
TI  - When information sharing is not enough.
AB  - This paper explores information sharing in multidisciplinary clinical
      collaboration between three hospitals. Our study draws on qualitative interviews
      with surgeons and radiologists in two county hospitals and one university
      hospital. The analysis shows that the actors shared a restricted amount of
      information about the patients they have in common and that different actors used
      the shared information in different ways. However, much communication was still
      needed to clarify and negotiate the meaning of shared data and its implications
      for collaborative care. To conclude, while the arguments for a shared information
      space may appear convincing, the communication practice observed should
      illustrate that IS also needs to support the communicative process in clinical
      collaborative work.

PMID- 21893774
TI  - Information and communication needs of healthcare workers in the perioperative
      domain.
AB  - Perioperative work requires the collaborative efforts of a multitude of actors.
      Coordinating such collaboration is challenging, and coordination breakdowns may
      be very expensive and jeopardize patient safety. We studied the needs for status
      information and projection of future status and events for key actors in the
      perioperative environment. We found that information and projection needs
      differed significantly between actors. While just-in-time notifications sufficed
      for some, others were dependent on projections to provide high quality and
      efficient care. Finally, information on current status and support in projecting
      the future unfolding of events could improve actors situated coordination
      capabilities.

PMID- 21893775
TI  - Clinical situations and information needs of physicians during treatment of
      diabetes mellitus patients: a triangulation study.
AB  - Physicians should have access to the information they need to provide the most
      effective health care. Medical knowledge and patient-oriented information is
      dynamic and expanding rapidly so there is a rising risk of information overload.
      We investigated the information needs of physicians during treatment of Diabetes
      mellitus patients, using a combination of interviews, observations, literature
      research and analysis of recorded medical information in hospitals as part of a
      methodical triangulation. 446 information items were identified, structured in a
      set of 9 main categories each, as well as 6 time windows, 10 clinical situations
      and 68 brief queries. The physician's information needs as identified in this
      study will now be used to develop sophisticated query tools to efficiently
      support finding of information in an electronic health record.

PMID- 21893776
TI  - A constructivist approach? using formative evaluation to inform the electronic
      prescription service implementation in primary care, England.
AB  - As part of the National Programme for IT (NPfIT) in England, the Electronic
      Prescription Service (EPS) is being implemented in two releases. The first
      release placed barcodes on prescriptions and is widely implemented. Release two
      (EPS2), the electronic transmission of prescriptions between GP, pharmacy and the
      reimbursement body, has just started implementation. On the NPfIT agenda,
      community pharmacies have been predicted to benefit from changes in work practice
      following the full EPS implementation. The study focused on how the advanced EPS
      (EPS2) might alter dispensing work practice in community pharmacies on issues
      such as workflow and workload; and the bearing of these issues on improvement in
      quality of service and safety. This paper demonstrates how findings of the pre
      implementation study were used to provide formative feedback to the implementers.
      A mixed ethnographical method that combined non- participant observations,
      shadowing and interviews, before and after implementation, was used to
      qualitatively study eight community pharmacies across three early adopter Primary
      Care Trusts (PCTs) in England. Key implementation issues were fed-back to the
      PCTs as part of the EPS2 rolling-out process. Staff access to dispensing
      terminals needs to be improved if electronic dispensing is to be encouraged.
      Also, as a safety issue, pharmacists are planning to print off electronic
      prescriptions (tokens) and dispense from them. Although safer, this could
      increase workload. The EPS2 could positively alter work practice by improving
      certain demanding aspects of dispensing whilst reducing human errors. For
      example, the high demand of customers handing in prescriptions and waiting for
      them to be dispensed could be reduced through automation. Also, the extreme
      variation in workload during various times of the day could be evened out to
      improve workflow and provide a better service; however, in order for this to be
      fully realized, technical issues such as number of staff per dispensing station
      and dispensing from tokens would need to be addressed.

PMID- 21893777
TI  - Can cloud computing benefit health services? - a SWOT analysis.
AB  - In this paper, we discuss cloud computing, the current state of cloud computing
      in healthcare, and the challenges and opportunities of adopting cloud computing
      in healthcare. A Strengths, Weaknesses, Opportunities and Threats (SWOT) analysis
      was used to evaluate the feasibility of adopting this computing model in
      healthcare. The paper concludes that cloud computing could have huge benefits for
      healthcare but there are a number of issues that will need to be addressed before
      its widespread use in healthcare.

PMID- 21893778
TI  - Medical providers' dental information needs: a baseline survey.
AB  - Articulation of medical and dental practices has been strongly called for based
      on the many oral-systemic connections. With the rapid development and adoption of
      electronic health records, the feasibility of integrating medical and dental
      patient data should be strongly considered. The objective of this study was to
      develop an initial understanding of the medical providers' core dental
      information needs and opinion of integrated medical-dental electronic health
      record (iEHR) environment in their workflow. This was achieved by administering a
      13 question survey to a group of 1,197 medical care providers employed by
      Marshfield Clinic in Wisconsin, United States. The survey received a response
      rate of 35%. The responses were analyzed based on provider 'Role' and
      'Specialty'. The majority of the respondents felt the need for patient's dental
      information to coordinate or provide effective medical care. An integrated
      electronic health record environment could facilitate this holistic patient care
      approach.

PMID- 21893779
TI  - What makes an information system more preferable for clinicians? a qualitative
      comparison of two systems.
AB  - Two different information systems with respect to their ability to afford
      clinicians' needs in the chemotherapy medication process were implemented in a
      large Dutch academic hospital. A commercially available Computerized Physician
      Order Entry (CPOE) system was not appreciated because clinicians believed that it
      could not support complex chemotherapy process. Later, a home-grown IT system
      with the capability of prescribing chemotherapy medications based on standard
      care protocols was appreciated and fully used by clinicians. We evaluated both
      systems from their users' perspective to find the sources of clinicians'
      preference and to trace them back to their Systems Development Life Cycle (SDLC).

PMID- 21893780
TI  - Does PACS facilitate work practice innovation in the intensive care unit?
AB  - Picture Archiving and Communication Systems (PACS) allow the fast delivery of
      imaging studies to clinicians at the point-of-care, supporting quicker decision
      making. PACS has the potential to have a significant impact in the Intensive Care
      Unit (ICU) where critical decisions are made on a daily basis, particularly
      during ward rounds. We aimed to examine how accessing image information is
      integrated into ward rounds and if the presence of PACS produced innovations in
      ward round practices. We observed ward rounds and conducted interviews with ICU
      doctors at three hospitals with differing levels of PACS availability and
      computerization. Imaging results were infrequently viewed by clinicians during
      ward rounds in two ICUs: one without PACS and one which had both PACS and bedside
      computers. In the third ICU, where PACS was only available at a central
      workstation, images were frequently viewed throughout the daily round and
      integrated into decisions about patient care. The presence of bedside computers
      does not automatically result in innovations to work practice. Despite the
      ability to utilize PACS at the bedside to support decision-making, use was
      varied. Research to understand how the complexities and context of the ICU
      contribute to work practice innovation and why practice changes differ is
      required.

PMID- 21893781
TI  - Innovation in intensive care nursing work practices with PACS.
AB  - Doctors are the main users of x-rays and other medical images in hospitals and as
      such picture archive and communication systems (PACS) have been designed to
      improve their work processes and clinical care by providing them with faster
      access to images. Nurses working in intensive care units (ICUs) also access
      images as an integral part of their work, yet no studies have examined the impact
      of PACS on the work of intensive care nurses. Our study aimed to examine whether
      and how ICU nurses view and use images and whether access to PACS promotes
      innovation in work practices. We interviewed (n=49) and observed (n=23) nurses in
      three Australian metropolitan teaching hospital ICUs with varying degrees of PACS
      implementation. Our study found that nurses with access to PACS were able to
      independently and easily access images, did so more frequently when required, and
      perceived that this had the potential to positively impact upon patient safety.
      Those without PACS usually viewed images more traditionally as part of a ward
      round. The introduction of PACS to ICU settings promotes changes in nursing work
      practices by providing nurses with the ability to act more autonomously, with the
      potential to enhance patient care.

PMID- 21893782
TI  - Evaluation of telephone triage and advice services: a systematic review on
      methods, metrics and results.
AB  - Telephone triage and advice services (TTAS) have been increasingly used to assess
      patients' symptoms, provide information and refer patients to appropriate levels
      of care (attempting to pursue efficiency and quality of care gains while ensuring
      safety). However, previous reviews have pointed out for the need for adequately
      evaluating TTAS. AIMS: To review TTAS evaluation studies, compile methodologies
      and metrics used and compare results. Systematic search in PubMed database; data
      collection and categorization by TTAS features and context, type of evaluation,
      methods, metrics and results; critical assessment of studies; discussion on
      research needs. 395 articles screened, 55 of them included in the analysis. In
      conclusion, several aspects of TTAS impact on healthcare systems remain unclear
      either due to a lack of research (e.g. on long term clinical outcomes, clinical
      pathways, safety, enhanced access) or because of huge disparities in existing
      studies on the accuracy of advice, patient compliance, system use, satisfaction
      and economic evaluation. Further research on TTAS impact is required, comprising
      multiple perspectives and broad range of metrics.

PMID- 21893783
TI  - Human factors based recommendations for the design of medication related clinical
      decision support systems (CDSS).
AB  - This study is part of a research project aiming at developing advanced functions
      of medication related CDSS to support the monitoring of patients' therapeutic
      treatments based mainly on corresponding lab values. We adopted a user-centred
      approach to the design of these advanced CDSS functions. We collected existing
      recommendations in the literature and completed previous Human Factors (HF) field
      studies and analyses by focused observations and modeling. We present resulting
      HF based recommendations for the design of such advanced medication CDSS and
      focus more specifically on two innovative high level recommendations completing
      those already existing in the literature. For illustration purposes, an example
      of the operationalization of one of the recommendation is presented.

PMID- 21893784
TI  - Making a web based ulcer record work by aligning architecture, legislation and
      users - a formative evaluation study.
AB  - The University Hospital of North Norway selected a web-based ulcer record used in
      Denmark, available from mobile phones. Data was stored in a common database and
      easily accessible. According to Norwegian legislation, only employees of the
      organization that owns an IT system can access the system, and use of mobile
      units requires strong security solutions. The system had to be changed. The paper
      addresses interactions in order to make the system legal, and assesses
      regulations that followed. By addressing conflicting scripts and the contingent
      nature of knowledge, we conducted a formative evaluation aiming at improving the
      object being studied. Participatory observation in a one year process, minutes
      from meetings and information from participants, constitute the data material. In
      the technological domain, one database was replaced by four. In the health care
      delivery domain, easy access was replaced by a more complicated log on procedure,
      and in the domain of law and security, a clarification of risk levels was
      obtained, thereby allowing for access by mobile phones with today's
      authentication mechanisms. Flexibility concerning predefined scripts was
      important in all domains. Changes were made that improved the platform for
      further development of legitimate communication of patient data via mobile units.
      The study also shows the value of formative evaluations in innovations.

PMID- 21893785
TI  - Assessing the role of a site visit in adopting activity driven methods.
AB  - Healthcare activities rely heavily on socio-technical information systems. Such
      systems should be developed according to a socio-technical approach. The Activity
      Driven (AD) approach has been developed to contribute to the early phases of
      information system development in healthcare. Multi-professional and multi
      disciplinary education in teams has been used to introduce the approach to
      prospective analysts, including "lay" healthcare professionals. 'Almost real life
      cases' have been emphasized as promoters of learning. This paper reports on a
      study on site visits as a crucial element for adopting socio-technical methods of
      analysis in healthcare. The paper presents feedback collected from an intensive
      course on health information systems development held in Mozambique. The results
      indicate the high importance of site visits - not only as a starting point of
      system analysis but also as a crucial promoter to learning socio-technical
      methods. Based on the results, needs for improvements are identified to the
      usability of AD tools and to the practical arrangements of site visits.

PMID- 21893786
TI  - A multi-method study of factors associated with hospital information system
      success in South Africa.
AB  - A combination of interpretivist and positivist techniques was used to develop and
      refine a conceptual model of factors associated with computerised hospital
      information system (CHIS) success in South Africa. Data from three case studies
      of CHIS use in level 2 public sector hospitals were combined to develop a
      conceptual model containing seven factors associated with CHIS success at
      hospital level. This conceptual model formed the basis of a fourth case study
      which aimed to confirm and refine the initial conceptual model. In the third
      phase of the study, a survey of CHIS use was conducted in 30 hospitals across two
      South African provinces, each using one of three different CHISs. Relationships
      between hospital-level factors of the conceptual model and user assessment of
      CHIS success were examined. A revised conceptual model of CHIS use was developed
      on the basis of the survey results. The use of a multi-method approach made it
      possible to generalise results from the case studies to multiple CHIS
      implementations in two provinces.

PMID- 21893787
TI  - Assessing biocomputational modelling in transforming clinical guidelines for
      osteoporosis management.
AB  - Biocomputational modelling as developed by the European Virtual Physiological
      Human (VPH) Initiative is the area of ICT most likely to revolutionise in the
      longer term the practice of medicine. Using the example of osteoporosis
      management, a socio-economic assessment framework is presented that captures how
      the transformation of clinical guidelines through VPH models can be evaluated.
      Applied to the Osteoporotic Virtual Physiological Human Project, a consequent
      benefit-cost analysis delivers promising results, both methodologically and
      substantially.

PMID- 21893788
TI  - Technical data evaluation of a palliative care web-based documentation system.
AB  - A technical analysis of the web-based patient documentation system, eKernPaP, was
      conducted. The system is used by interdisciplinary pediatric palliative care
      teams in Germany to document outpatient care. The data of the system and the data
      of an external web analytic system have been evaluated. The results gave an
      overview how the system is used and what information is generated. A detailed
      analysis of singular forms showed that not all forms were filled in completely.
      With the help of the external web analytic system the navigation behavior of the
      users could be retraced. The users followed the given navigation from top to
      bottom. An existing exception in this pattern turned out to be misplacement and
      will be corrected in the next version. The technical analysis proved to be a good
      tool for improving a web-based documentation system.

PMID- 21893789
TI  - Extracting gait parameters from raw electronic walkway data.
AB  - Spatiotemporal gait parameters are very important for the detection of gait
      impairments and associated conditions. Current methods to measure such
      parameters, e.g. electronic walkways or force plates, are costly and can only be
      used in a laboratory. The new generation of raw data accelerometers might be a
      cheap and flexible alternative. We conducted a small feasibility study with 50
      subjects from the KORA-Age project exploring the output of GAITRite and Actigraph
      GT3X. We open-sourced a package to extract and process raw data from GAITRite.
      The most promising location for the accelerometer seems to be at the ankle. The
      use of accelerometers showed to be simple and reliable, indicating that they can
      be used in daily life to extract gait parameters.

PMID- 21893790
TI  - Safe storage and multi-modal search for medical images.
AB  - Modern hospitals produce enormous amounts of data in all departments, from
      images, to lab results, medication use, and release letters. Since several years
      these data are most often produced in digital form, making them accessible for
      researchers to optimize the outcome of care process and analyze all available
      data across patients. The Geneva University Hospitals (HUG) are no exception with
      its daily radiology department's output of over 140'000 images in 2010, with a
      majority of them being tomographic slices. In this paper we introduce tools for
      uploading and accessing DICOM images and associated metadata in a secure Grid
      storage. These data are made available for authorized persons using a Grid
      security framework, as security is a main problem in secondary use of image data,
      where images are to be stored outside of the clinical image archive. Our tool
      combines the security and metadata access of a Grid middleware with the visual
      search that uses GIFT.

PMID- 21893791
TI  - Respiration tracking using the Wii remote game controller.
AB  - Respiration exercises are an important part in the pulmonary rehabilitation of
      COPD (chronic obstructive pulmonary disease) patients. Furthermore, previous
      research has demonstrated that showing respiration pattern helps the patients to
      improve their breathing skills. We have developed a low cost and non-invasive
      prototype based on the Wii remote game controller infrared camera to provide BPM
      (breaths per minute) measurement as feedback. It can also be a comfortable
      solution without wires, batteries or any kind of electronics but just wearing
      passive markers. The lab evaluation with 7 healthy individuals showed that this
      approach is feasible when users are resting of their exercise. The BPM monitored
      during the tests presented less than 15% of maximum error and the RMSE (root mean
      square error) was lower than 6% in all the tests. Further research is needed to
      evaluate and adapt the system for COPD patients. In addition, more work is needed
      to develop applications that can be built to motivate and guide the users.

PMID- 21893792
TI  - A nomenclature for the analysis of continuous sensor and other data in the
      context of health-enabling technologies.
AB  - Due to the progress in technology, it is possible to capture continuous sensor
      data pervasively and ubiquitously. In the area of health-enabling and ambient
      assisted technologies we are faced with the problem of analyzing these data in
      order to improve or at least maintain the health status of patients. But due to
      the interdisciplinarity of this field every discipline makes use of their own
      analyzing methods. In fact, the choice of a certain analyzing method often solely
      depends on the set of methods known to the data analyst. It would be an advantage
      if the data analyst would know about all available analyzing methods and their
      advantages and disadvantages when applied to the manifold of data. In this paper
      we propose a nomenclature that structures existing analyzing methods and assists
      in the choice of a certain method that fits to a given measurement context and a
      given problem.

PMID- 21893793
TI  - Image-based classification of parkinsonian syndromes using T2'-atlases.
AB  - Parkinsonian syndromes (PS) are genetically and pathologically heterogeneous
      neurodegenerative disorders. Clinical distinction between different PS can be
      difficult, particularly in early disease stages. This paper describes an
      automatic method for the distinction between classical Parkinson's disease (PD)
      and progressive supranuclear palsy (PSP) using T2' atlases. This procedure is
      based on the assumption that regional brain iron content differs between PD and
      PSP, which can be selectively measured using T2' MR imaging. The proposed method
      was developed and validated based on 33 PD patients, 10 PSP patients, and 24
      healthy controls. The first step of the proposed procedure comprises T2' atlas
      generation for each group using affine and following non-linear registration. For
      classification, a T2' dataset is registered to the atlases and compared to each
      one of them using the mean sum of squared differences metric. The dataset is
      assigned to the group for which the corresponding atlas yields the lowest value.
      The evaluation using leave-one-out validation revealed that the proposed method
      achieves a classification accuracy of 91%. The presented method might serve as
      the basis for an improved automatic classification of PS in the future.

PMID- 21893794
TI  - Cell edge detection in JPEG2000 wavelet domain - analysis on sigmoid function
      edge model.
AB  - Big virtual microscopy images (80K x 60K pixels and larger) are usually stored
      using the JPEG2000 image compression scheme. Diagnostic quantification, based on
      image analysis, might be faster if performed on compressed data (approx. 20 times
      less the original amount), representing the coefficients of the wavelet
      transform. The analysis of possible edge detection without reverse wavelet
      transform is presented in the paper. Two edge detection methods, suitable for
      JPEG2000 bi-orthogonal wavelets, are proposed. The methods are adjusted according
      calculated parameters of sigmoid edge model. The results of model analysis
      indicate more suitable method for given bi-orthogonal wavelet.

PMID- 21893796
TI  - Defining and reconstructing clinical processes based on IHE and BPMN 2.0.
AB  - This paper describes the current status and the results of our process management
      system for defining and reconstructing clinical care processes, which contributes
      to compare, analyze and evaluate clinical processes and further to identify high
      cost tasks or stays. The system is founded on IHE, which guarantees standardized
      interfaces and interoperability between clinical information systems. At the
      heart of the system there is BPMN, a modeling notation and specification
      language, which allows the definition and execution of clinical processes. The
      system provides functionality to define healthcare information system independent
      clinical core processes and to execute the processes in a workflow engine.
      Furthermore, the reconstruction of clinical processes is done by evaluating an
      IHE audit log database, which records patient movements within a health care
      facility. The main goal of the system is to assist hospital operators and
      clinical process managers to detect discrepancies between defined and actual
      clinical processes and as well to identify main causes of high medical costs.
      Beyond that, the system can potentially contribute to reconstruct and improve
      clinical processes and enhance cost control and patient care quality.

PMID- 21893795
TI  - Using multimodal mining to drive clinical guidelines development.
AB  - We present exploratory investigations of multimodal mining to help designing
      clinical guidelines for antibiotherapy. Our approach is based on the assumption
      that combining various sources of data, such as the literature, a clinical
      datawarehouse, as well as information regarding costs will result in better
      recommendations. Compared to our baseline recommendation system based on a
      question-answering engine built on top of PubMed, an improvement of +16% is
      observed when clinical data (i.e. resistance profiles) are injected into the
      model. In complement to PubMed, an alternative search strategy is reported, which
      is significantly improved by the use of the combined multimodal approach. These
      results suggest that combining literature-based discovery with structured data
      mining can significantly improve effectiveness of decision-support systems for
      authors of clinical practice guidelines.

PMID- 21893797
TI  - Facilitating access to laboratory guidelines by modeling their contents and
      designing a computerized user interface.
AB  - Laboratory tests are not always prescribed appropriately. Guidelines for some
      important laboratory tests have been developed by expert panels in the Parisian
      region to maximize the appropriateness of laboratory medicine. However; these
      recommendations are not frequently consulted by physicians and nurses. We
      developed a system facilitating consultation of these guidelines, to increase
      their usability. Elements of information contained in these documents were
      identified and included in recommendations of different categories. UML modeling
      was used to represent these categories and their relationships to each other in
      the guidelines. We used the generated model to implement a computerized
      interface. The prototype interface, based on web-based technology was found to be
      rapid and easy to use. By clicking on provided keywords, information about the
      subject sought is highlighted whilst retaining the entire text of the guideline
      on-screen.

PMID- 21893798
TI  - Evaluation of multi-terminology super-concepts for information retrieval.
AB  - BACKGROUND: Following a recent change in the indexing policy for French quality
      controlled health gateway CISMeF, multiple terminologies are now being used for
      indexing in addition to MeSH(r). OBJECTIVE: To evaluate precision and recall of
      super-concepts for information retrieval in a multi-terminology paradigm compared
      to MeSH-only. METHODS: We evaluate the relevance of resources retrieved by multi
      terminology super-concepts and MeSH-only super-concepts queries. RESULTS: Recall
      was 8-14% higher for multi-terminology super-concepts compared to MeSH only super
      concepts. Precision decreased from 0.66 for MeSH only super-concepts to 0.61 for
      multi-terminology super-concepts. Retrieval performance was found to vary
      significantly depending on the super-concepts (p<10<sup>-4</sup>) and indexing
      methods (manual vs automatic; p<0.004). CONCLUSION: A multi-terminology paradigm
      contributes to increase recall but lowers precision. Automated tools for indexing
      are not accurate enough to allow a very precise information retrieval.

PMID- 21893799
TI  - Framework model and principles for trusted information sharing in pervasive
      health.
AB  - Trustfulness (i.e. health and wellness information is processed ethically, and
      privacy is guaranteed) is one of the cornerstones for future Personal Health
      Systems, ubiquitous healthcare and pervasive health. Trust in today's healthcare
      is organizational, static and predefined. Pervasive health takes place in an open
      and untrusted information space where person's lifelong health and wellness
      information together with contextual data are dynamically collected and used by
      many stakeholders. This generates new threats that do not exist in today's
      eHealth systems. Our analysis shows that the way security and trust are
      implemented in today's healthcare cannot guarantee information autonomy and
      trustfulness in pervasive health. Based on a framework model of pervasive health
      and risks analysis of ubiquitous information space, we have formulated principles
      which enable trusted information sharing in pervasive health. Principles imply
      that the data subject should have the right to dynamically verify trust and to
      control the use of her health information, as well as the right to set situation
      based context-aware personal policies. Data collectors and processors have
      responsibilities including transparency of information processing, and openness
      of interests, policies and environmental features. Our principles create a base
      for successful management of privacy and information autonomy in pervasive
      health. They also imply that it is necessary to create new data models for
      personal health information and new architectures which support situation
      depending trust and privacy management.

PMID- 21893800
TI  - Populating the i2b2 database with heterogeneous EMR data: a semantic network
      approach.
AB  - In an ongoing effort to share heterogeneous electronic medical record (EMR) data
      in an i2b2 instance between the University Hospitals Munster and Erlangen for
      joint cancer research projects, an ontology based system for the mapping of EMR
      data to a set of common data elements has been developed. The system translates
      the mappings into local SQL scripts, which are then used to extract, transform
      and load the facts data from each EMR into the i2b2 database. By using Semantic
      Web standards, it is the authors' goal to reuse the laboriously compiled "mapping
      knowledge" in future projects, such as a comprehensive cancer ontology or even a
      hospital-wide clinical ontology.

PMID- 21893801
TI  - A novel way of standardized and automized retrieval of timing information along
      clinical pathways.
AB  - Improving the effectiveness and efficiency of acute healthcare is very important
      nowadays. Optimization of clinical pathways regarding quality, time and costs is
      one of the key management strategies of critical diseases such as heart attack
      and stroke. To identify workflow bottlenecks requires a thorough understanding
      about both the hospital environment (e.g. IT-systems) and processes (e.g.
      clinical pathways). Having in mind the interoperability issues in hospitals, the
      standardized division- and system-crossing time measurement is still a challenge.
      Therefore this paper presents a novel way of structured and standardized
      retrieval of timing information along the clinical pathway of time-critical
      diseases in the context of hospital IT-systems, which represents a promising
      opportunity to identify workflow bottlenecks over several departmental and system
      borders.

PMID- 21893802
TI  - Computing the compliance of physician drug orders with guidelines using an OWL2
      reasoner and standard drug resources.
AB  - Assessing the conformity of a physician's prescription to a given recommended
      prescription is not obvious since both prescriptions are expressed at different
      levels of abstraction and may concern only a subpart of the whole order. Recent
      formalisms (OWL2) and tools (reasoners) from the semantic web technologies are
      becoming available to represent defined concepts and to handle classification
      services. We propose a generic framework based on such technologies, using
      available standardized drug resources, to compute the compliance of a given drug
      order to a recommended prescription, such that the subsumption relationship
      yields the conformity relationship between the order and the recommendation. The
      ATC drug classification has been used as a local ontology. The method has been
      successfully implemented for arterial hypertension management for which we had a
      sample of antihypertensive orders. However, supplemental standardized drug
      knowledge is needed to correctly compare drug orders to recommended orders.

PMID- 21893803
TI  - Automatic definition of the oncologic EHR data elements from NCIT in OWL.
AB  - Semantic interoperability based on ontologies allows systems to combine their
      information and process them automatically. The ability to extract meaningful
      fragments from ontology is a key for the ontology re-use and the construction of
      a subset will help to structure clinical data entries. The aim of this work is to
      provide a method for extracting a set of concepts for a specific domain, in order
      to help to define data elements of an oncologic EHR. METHOD: a generic extraction
      algorithm was developed to extract, from the NCIT and for a specific disease
      (i.e. prostate neoplasm), all the concepts of interest into a sub-ontology. We
      compared all the concepts extracted to the concepts encoded manually contained
      into the multi-disciplinary meeting report form (MDMRF). RESULTS: We extracted
      two sub-ontologies: sub-ontology 1 by using a single key concept and sub-ontology
      2 by using 5 additional keywords. The coverage of sub-ontology 2 to the MDMRF
      concepts was 51%. The low rate of coverage is due to the lack of definition or
      mis-classification of the NCIT concepts. By providing a subset of concepts
      focused on a particular domain, this extraction method helps at optimizing the
      binding process of data elements and at maintaining and enriching a domain
      ontology.

PMID- 21893804
TI  - Developing a model for the adequate description of electronic communication in
      hospitals.
AB  - Adequate information and communication systems (ICT) can help to improve the
      communication in hospitals. Changes to the ICT-infrastructure of hospitals must
      be planed carefully. In order to support a comprehensive planning, we presented a
      classification of 81 common errors of the electronic communication on the MIE
      2008 congress. Our objective now was to develop a data model that defines
      specific requirements for an adequate description of electronic communication
      processes We first applied the method of explicating qualitative content analysis
      on the error categorization in order to determine the essential process details.
      After this, we applied the method of subsuming qualitative content analysis on
      the results of the first step. A data model for the adequate description of
      electronic communication. This model comprises 61 entities and 91 relationships.
      The data model comprises and organizes all details that are necessary for the
      detection of the respective errors. It can be for either used to extend the
      capabilities of existing modeling methods or as a basis for the development of a
      new approach.

PMID- 21893805
TI  - Contextualization in automatic extraction of drugs from hospital patient records.
AB  - Information Extraction (IE) from medical texts aims at the automatic recognition
      of entities and relations of interests. IE is based on shallow analysis and
      considers only sentences containing important words. Thus IE of drugs from
      discharge letters can identify as 'current' some past or future medication
      events. This article presents heuristic observations enabling to filter drugs
      that are taken by the patients during the hospitalization. These heuristics are
      based on the default PR structure and linguistic expressions signaling temporal
      and conditional markers. They are integrated in a system for drug extraction from
      hospital Patient Records (PRs) in Bulgarian language. Present evaluation results
      are summarized as well.

PMID- 21893806
TI  - Revisiting the area under the ROC.
AB  - The Receiver-Operating Characteristic curve or ROC has been a long standing and
      well appreciated tool to assess performance of classifiers or diagnostic tests.
      Likewise, the Area Under the ROC (AUC) has been a metric to summarize the power
      of a test or ability of a classifier in one measurement. This article aims to
      revisit the AUC, and ties it to key characteristics of the noncentral
      hypergeometric distribution. It is demonstrated that this statistical
      distribution can be used in modeling the behaviour of classifiers, which is of
      value for comparing classifiers.

PMID- 21893807
TI  - Service delivery for e-Health applications.
AB  - E-Health applications have to take the business perspective into account. This is
      achieved by adding a fourth layer reflecting organizational and business
      processes to an existing three layer model for IT-system functionality and
      management. This approach is used for designing a state-wide e-Health service
      delivery allowing for distributed responsibilities: clinical organizations act on
      the fourth layer and have established mutual cooperation in this state-wide
      approach based on collectively outsourced IT-system services. As a result, no
      clinical organization can take a dominant role based on operating the IT-system
      infrastructure. The implementation relies on a central infrastructure with
      extended means to guarantee service delivery: (i) established redundancy within
      the system architecture, (ii) actively controlled network and application
      availability, (iii) automated routine performance tests fulfilling regulatory
      requirements and (iv) hub-to-spoke and end-to-end authentication. As a result,
      about half of the hospitals and some practices of the state have signed-up to the
      services and guarantee long-term sustainability by sharing the infrastructural
      costs. Collaboration takes place for more than 1000 patients per month based on
      second opinion, online consultation and proxy services for weekend and night
      shifts.

PMID- 21893808
TI  - A KPI framework for process-based benchmarking of hospital information systems.
AB  - Benchmarking is a major topic for monitoring, directing and elucidating the
      performance of hospital information systems (HIS). Current approaches neglect the
      outcome of the processes that are supported by the HIS and their contribution to
      the hospital's strategic goals. We suggest to benchmark HIS based on clinical
      documentation processes and their outcome. A framework consisting of a general
      process model and outcome criteria for clinical documentation processes is
      introduced.

PMID- 21893809
TI  - Medical knowledge evolution query constraining aspects.
AB  - In this paper we present a first analysis towards better understanding of the
      query constraining aspects of knowledge, as expressed in the most used public
      medical bibliographic database MEDLINE. Our results indicate, possibly not
      surprising, that new terms occur, but also that traditional terms are replaced by
      more specific ones or even go out of use as they become common knowledge. Hence,
      as knowledge evolve over time, search methods may benefit from becoming more
      sensitive to knowledge expression, to enable finding new, as well as older,
      relevant database contents.

PMID- 21893810
TI  - Optimal asymmetrical SVM using pattern search. A health care application.
AB  - This paper considers the model selection problem for Support Vector Machines. A
      well-known derivative Pattern Search method, which aims to tune hyperparameter
      values using an empirical error estimate as a steering criterion, is proposed.
      This approach is experimentally evaluated on a health care problem which involves
      discriminating nosocomially infected patients from non-infected patients. The
      Hooke and Jeeves Pattern Search (HJPS) method is shown to improve the results
      achieved by Grid Search (GS) in terms of solution quality and computational
      efficiency. Unlike most other parameter tuning techniques, our approach does not
      require supplementary effort such as computation of derivatives, making them well
      suited for practical purposes. This method produces encouraging results: it
      exhibits good performance and convergence properties.

PMID- 21893811
TI  - Factuality levels of diagnoses in Swedish clinical text.
AB  - Different levels of knowledge certainty, or factuality levels, are expressed in
      clinical health record documentation. This information is currently not fully
      exploited, as the subtleties expressed in natural language cannot easily be
      machine analyzed. Extracting relevant information from knowledge-intensive
      resources such as electronic health records can be used for improving health care
      in general by e.g. building automated information access systems. We present an
      annotation model of six factuality levels linked to diagnoses in Swedish clinical
      assessments from an emergency ward. Our main findings are that overall agreement
      is fairly high (0.7/0.58 F-measure, 0.73/0.6 Cohen's kappa, Intra/Inter). These
      distinctions are important for knowledge models, since only approx. 50% of the
      diagnoses are affirmed with certainty. Moreover, our results indicate that there
      are patterns inherent in the diagnosis expressions themselves conveying
      factuality levels, showing that certainty is not only dependent on context cues.

PMID- 21893812
TI  - Network analysis of possible anaphylaxis cases reported to the US vaccine adverse
      event reporting system after H1N1 influenza vaccine.
AB  - The identification of signals from spontaneous reporting systems plays an
      important role in monitoring the safety of medical products. Network analysis
      (NA) allows the representation of complex interactions among the key elements of
      such systems. We developed a network for a subset of the US Vaccine Adverse Event
      Reporting System (VAERS) by representing the vaccines/adverse events (AEs) and
      their interconnections as the nodes and the edges, respectively; this subset we
      focused upon included possible anaphylaxis reports that were submitted for the
      H1N1 influenza vaccine. Subsequently, we calculated the main metrics that
      characterize the connectivity of the nodes and applied the island algorithm to
      identify the densest region in the network and, thus, identify potential safety
      signals. AEs associated with anaphylaxis formed a dense region in the
      'anaphylaxis' network demonstrating the strength of NA techniques for pattern
      recognition. Additional validation and development of this approach is needed to
      improve future pharmacovigilance efforts.

PMID- 21893813
TI  - Using pharmacogenetics knowledge to increase accuracy of alerts for adverse drug
      events.
AB  - Adverse drug event (ADE) has significant implications on patient safety and is
      recognized as a major cause of fatalities and hospital expenses. Although some
      medical systems today can help reduce the number of ADE occurrences, these
      primarily take into account clinical factors-even though recent studies show the
      significance of genetic profiles in ADE detection. Incorporating pharmacogenetics
      knowledge and data from genetic test results into these systems can improve the
      accuracy of preliminary alerts about potential ADEs. However, pharmacogenetics
      knowledge is unstructured, making it inappropriate for use in a system that
      involves automatic processing. We propose a methodology that can help incorporate
      the pharmacogenetics knowledge. Specifically, we show how pharmacogenetics
      knowledge can be expressed in a medical system and used together with the patient
      genetic data to provide alerts about ADEs at the point of care.

PMID- 21893814
TI  - Schizophrenia prediction with the adaboost algorithm.
AB  - This paper presents an adaBoost approach for schizophrenia relapse prediction.
      The data for the adaBoost are extracted from patients answers to Early Warning
      Signs questionnaires sent regularly via mobile phone messages. The performance of
      the adaBoost algorithm is confronted with current ITAREPS system with sensitivity
      0.65 and specificity 0.73. AdaBoost has the same sensitivity 0.65 but higher
      specificity 0.84 and is then ready to became the part of the ITAREPS care
      program.

PMID- 21893815
TI  - Applying one-vs-one and one-vs-all classifiers in k-nearest neighbour method and
      support vector machines to an otoneurological multi-class problem.
AB  - We studied how the splitting of a multi-class classification problem into
      multiple binary classification tasks, like One-vs-One (OVO) and One-vs-All (OVA),
      affects the predictive accuracy of disease classes. Classifiers were tested with
      an otoneurological data using 10-fold cross-validation 10 times with k-Nearest
      Neighbour (k-NN) method and Support Vector Machines (SVM). The results showed
      that the use of multiple binary classifiers improves the classification
      accuracies of disease classes compared to one multi-class classifier. In general,
      OVO classifiers worked out better with this data than OVA classifiers.
      Especially, the OVO with k-NN yielded the highest total classification
      accuracies.

PMID- 21893816
TI  - Roogle: an information retrieval engine for clinical data warehouse.
AB  - High amount of relevant information is contained in reports stored in the
      electronic patient records and associated metadata. R-oogle is a project aiming
      at developing information retrieval engines adapted to these reports and designed
      for clinicians. The system consists in a data warehouse (full-text reports and
      structured data) imported from two different hospital information systems.
      Information retrieval is performed using metadata-based semantic and full-text
      search methods (as Google). Applications may be biomarkers identification in a
      translational approach, search of specific cases, and constitution of cohorts,
      professional practice evaluation, and quality control assessment.

PMID- 21893817
TI  - Truecasing clinical narratives.
AB  - Truecasing, or capitalization, is the rewriting of each word of an input text
      with its proper case information. Many medical texts, especially those from
      legacy systems, are still written entirely in capitalized letters, hampering
      their readability. We present a pilot study that uses the World Wide Web as a
      corpus in order to support automatic truecasing. The texts under scrutiny were
      German-language pathology reports. By submitting token bigrams to the Google Web
      search engine we collected enough case information so that we achieved 81.3%
      accuracy for acronyms and 98.5% accuracy for normal words. This is all the more
      impressive as only half of the words used in this corpus existed in a standard
      medical dictionary due to the excessive use of ad-hoc single-word nominal
      compounds in German. Our system performed less satisfactory for spelling
      correction, and in three cases the proposed word substitutions altered the
      meaning of the input sentence. For the routine deployment of this method the
      dependency on a (black box) search engine must be overcome, for example by using
      cloud-based Web n-gram services.

PMID- 21893818
TI  - Checking coding completeness by mining discharge summaries.
AB  - Incomplete coding is a known problem in hospital information systems. In order to
      detect non-coded secondary diseases we developed a text classification system
      which scans discharge summaries for drug names. Using a drug knowledge base in
      which drug names are linked to sets of ICD-10 codes, the system selects those
      documents in which a drug name occurs that is not justified by any ICD-10 code
      within the corresponding record in the patient database. Treatment episodes with
      missing codes for diabetes mellitus, Parkinson's disease, and asthma/COPD were
      subject to investigation in a large German university hospital. The precision of
      the method was 79%, 14%, and 45% respectively, roughly estimated recall values
      amounted to 43%, 70%, and 36%. Based on these data we predict roughly 716 non
      coded diabetes cases, 13 non-coded Parkinson cases, and 420 non-coded asthma/COPD
      cases among 34,865 treatment episodes.

PMID- 21893819
TI  - Healthcare professionals' experiences with EHR-system access control mechanisms.
AB  - Access control mechanisms might influence on the information seeking and
      documentation behavior of clinicians. In this study, we have surveyed healthcare
      professionals in nursing homes and hospitals on their attitudes to, and
      experiences with using access control mechanisms. In some situations, the access
      control mechanisms of the EHR system made clinicians postpone documentation work.
      Their practice of reading what others have documented was also influenced. Not
      all clinicians logged out of the system when they left a workstation, and some
      clinicians reported to do some of their documentation work in the name of others.
      The reported practices might have implications for the safety of the patient.

PMID- 21893820
TI  - Personal health information on display: balancing needs, usability and
      legislative requirements.
AB  - Large wall-mounted screens placed at locations where health personnel pass by
      will assist in self-coordination and improve utilisation of both resources and
      staff at hospitals. The sensitivity level of the information visible on these
      screens must be adapted to a close-to-public setting, as passers-by may not have
      the right or need to know anything about patients being treated. We have
      conducted six informal interviews with health personnel in order to map what kind
      of information they use when identifying their patients and their next tasks. We
      have compared their practice and needs to legislative requirements and conclude
      that it is difficult, if not impossible, to fulfil all requirements from all
      parties.

PMID- 21893821
TI  - Watermarking - a new way to bring evidence in case of telemedicine litigation.
AB  - When dealing with medical data sharing, in particular within telemedicine
      applications, there is a need to ensure information security. Being able to
      verify that the information belongs to the right patient and is from the right
      source or that it has been rerouted or modified is a major concern. Watermarking,
      which is the embedding of security elements, such as a digital signature, within
      a document, can help to ensure that a digital document is reliable. However, at
      the same time, questions arise about the validity of watermarking-based proof. In
      this paper, beyond the technical aspects, we discuss the legal acceptability of
      watermarking in the context of telemedicine applications.

PMID- 21893822
TI  - Sharing sensitive personal health information through Facebook: the unintended
      consequences.
AB  - The purpose of this paper was to explore the types of sensitive health
      information posted by individuals through social network media sites such as
      Facebook. The researcher found several instances in which individuals, who could
      be identified by their user profiles, posted personal and sensitive health
      information related to mental and genetic disorders and sexually transmitted
      diseases. The data suggest that Facebook users should be made aware of the
      potential harm that may occur when sharing sensitive health information publicly
      through Facebook. Ethical considerations in undertaking such research are also
      examined.

PMID- 21893823
TI  - End-to-end security for personal telehealth.
AB  - Personal telehealth is in rapid development with innovative emerging applications
      like disease management. With personal telehealth people participate in their own
      care supported by an open distributed system with health services. This poses new
      end-to-end security and privacy challenges. In this paper we introduce new end-to
      end security requirements and present a design for consent management in the
      context of the Continua Health Alliance architecture. Thus, we empower patients
      to control how their health information is shared and used in a personal
      telehealth eco-system.

PMID- 21893824
TI  - The epidemiologic surveillance of dengue-fever in French Guiana: when
      achievements trigger higher goals.
AB  - The epidemiology of dengue fever in French Guiana is marked by a combination of
      permanent transmission of the virus in the whole country and the occurrence of
      regular epidemics. Since 2006, a multi data source surveillance system was
      implemented to monitor dengue fever patterns, to improve early detection of
      outbreaks and to allow a better provision of information to health authorities,
      in order to guide and evaluate prevention activities and control measures. This
      report illustrates the validity and the performances of the system. We describe
      the experience gained by such a surveillance system and outline remaining
      challenges. Future works will consist in the use of other data sources such as
      environmental factors in order to improve knowledge on virus transmission
      mechanisms and determine how to use them for outbreaks prediction.

PMID- 21893825
TI  - Prescribing history to identify candidates for chronic condition medication
      adherence promotion.
AB  - Poor adherence to long-term prescription medication is a frequent problem that
      undermines pharmacological control of important risk factors such as
      hypertension. A medication possession ratio (MPR) can be calculated from Practice
      Management System (PMS) data to provide a convenient indicator of adherence. We
      investigate how well prior MPR predicts later MPR, taking MPR<80% as indicative
      of 'non-adherence,' to assess the potential value of MPR calculation on PMS data
      for targeting adherence promotion activities by general practices. We examine PMS
      data for two New Zealand metropolitan general practices, one with a predominantly
      Pacific caseload, across 2008 and 2009. We find prevalence of non-adherence in
      2009 to be 51.63% (95% confidence interval [CI] 47.9-55.3) for patients at the
      Pacific practice and 28.09% (95% CI 25.0-31.1) at the other practice for patients
      who are demonstrably active with the practice in 2009. The positive predictive
      value (PPV) of 2008 non-adherence for 2009 non-adherence is 71.80% (95% CI, 66.5
      77.1) and negative predictive value (NPV) 61.52% (95% CI 56.9-66.1) for the
      Pacific practice; PPV is 61.38% (95% CI 54.6-68.2) and NPV is 82.19% (95% CI 79.2
      85.2) for the other practice. The results indicate good potential for decision
      support tools to target adherence promotion.

PMID- 21893826
TI  - Challenges for signal generation from medical social media data.
AB  - Early detection of disease outbreaks is crucial for public health officials to
      react and report in time. Currently, novel approaches and sources of information
      are investigated to address this challenge. For example, data sources such as
      blogs or Twitter messages become increasingly important for epidemiologic
      surveillance. In traditional surveillance, statistical methods are used to
      interpret reported number of cases or other indicators to potential disease
      outbreaks. For analyzing data collected from other data sources, in particular
      for data extracted from unstructured text, it is still unclear whether these
      methods can be applied. This paper surveys existing methods for interpreting data
      for signal generation in public health. In particular, problems to be addressed
      when applying them to social media data will be summarized and future steps will
      be highlighted.

PMID- 21893827
TI  - Providing trust and interoperability to federate distributed biobanks.
AB  - Biomedical research requires large numbers of well annotated, quality-assessed
      samples which often cannot be provided by a single biobank. Connecting biobanks,
      researchers and service providers raises numerous challenges including trust
      among partners and towards the infrastructure as well as interoperability
      problems. Therefore we develop a holistic, open-source and easy-to-use IT
      infrastructure. Our federated approach allows partners to reflect their
      organizational structures and protect their data sovereignty. The search service
      and the contact arrangement processes increase data sovereignty without
      stigmatizing for rejecting a specific cooperation. The infrastructure supports
      daily processes with an integrated basic sample manager and user-definable
      electronic case report forms. Interfaces for existing IT systems avoid re
      entering of data. Moreover, resource virtualization is supported to make
      underutilized resources of some partners accessible to those with insufficient
      equipment for mutual benefit. The functionality of the resulting infrastructure
      is outlined in a use-case to demonstrate collaboration within a translational
      research network. Compared to other existing or upcoming infrastructures, our
      approach has ultimately the same goals, but relies on gentle incentives rather
      than top-down imposed progress.

PMID- 21893828
TI  - Web 2.0 in healthcare: state-of-the-art in the German health insurance landscape.
AB  - The Internet is increasingly used as a source for information and knowledge. Even
      in the field of healthcare, information is widely available. Patients and their
      relatives increasingly use the Internet in order to search for healthcare
      information and applications. "Health 2.0" - the increasing use of Web 2.0
      technologies and tools in Electronic Healthcare - promises new ways of
      interaction, communication, and participation for healthcare. In order to explore
      how Web 2.0 applications are in general adopted and implemented by health
      information providers, we analysed the websites of all German health insurances
      companies regarding their provision of Web 2.0 applications. As health insurances
      play a highly relevant role in the German healthcare system, we conduct an
      exploratory survey in order to provide answers about the adoption and
      implementation of Web 2.0 technologies. Hence, all 198 private and public health
      insurances were analysed according to their websites. The results show a wide
      spread diffusion of Web 2.0 applications but also huge differences between the
      implementation by the respective insurances. Therefore, our findings provide a
      foundation for further research on aspects that drive the adoption.

PMID- 21893829
TI  - Improving the transparency of health information found on the internet through
      the honcode: a comparative study.
AB  - This study aims to show that health websites not asking for HONcode certification
      (Control sample websites A) do not respect elementary ethical standards such as
      the HONcode. The HONcode quality and ethical standards and the certification
      process have been developed by the Health on the Net Foundation to improve the
      transparency of the health and medical information found on the Internet. We
      compared the compliance with the 8 HONcode principles, and respectively the
      respect of principles 1 (authority), 4 (assignment), 5 (justification) and 8
      (honesty in advertising and editorial policy) by certified websites (A) and by
      health websites which have not requested the certification (B). The assessment of
      the HONcode compliance was performed by HON evaluators by the same standards for
      all type of sites. Results shows that 0.6% of health websites not asking for
      HONcode certification does respect the eight HONcode ethical standards vs. 89% of
      certified websites. Regarding the principles 1, 4, 5 and 8, 1.2% of B respect
      these principles vs. 92% for A. The certification process led health websites to
      respect the ethical and quality standards such as the HONcode, and disclosing the
      production process of the health website.

PMID- 21893831
TI  - Relevance and usability of a computerized patient simulator for continuous
      medical education of isolated care professionals in sub-saharan Africa.
AB  - OBJECTIVE: to explore the relevance and usability of using a computerized patient
      simulator as a tool for continuous medical education and decision support for
      health professionals in district hospitals in Sub-Saharan Africa. METHODS: based
      on the diagnosis pathway and decision analysis in uncertainty context,
      interactive clinical vignettes are developed using VIPS, a computerized patient
      simulator, taking into account clinical problem situations whose relevance was
      identified. Vignettes were adapted to take into account local epidemiology,
      availability of diagnostic and therapeutic resources, and local socio-cultural
      constraints. The evaluation on VIPS software was made by care professionals and
      students. RESULTS: a computerized patient simulator can be used to provide
      initial and continuing medical education in Sub-Saharan Africa. But many
      challenges exist. CONCLUSION: further research is needed to measure potential
      improvements in knowledge, skills, decision-making abilities as well as patient
      outcome.

PMID- 21893830
TI  - Data privacy preservation in telemedicine: the PAIRSE project.
AB  - The preservation of medical data privacy and confidentiality is a major challenge
      in eHealth systems and applications. A technological solution based on advanced
      information and communication systems architectures is needed in order to
      retrieve and exchange the patient's data in a secure and reliable manner. In this
      paper, we introduce the project PAIRSE, Preserving Privacy in Peer to Peer (P2P)
      environments, which proposes an original web service oriented framework
      preserving the privacy and confidentiality of shared or exchanged medical data.

PMID- 21893832
TI  - Applications of medical intelligence in remote monitoring.
AB  - Prevention and rehabilitation efficiency can greatly benefit from the application
      of intelligent, 24 hour tele-diagnostics and tele-care information systems. Tele
      monitoring also supports a new level of medical supervision over the patient's
      lifestyle. In this paper we briefly present the architecture and development
      phase results of the Alpha remote monitoring system. The novelty of the system is
      the unified and flexible processing of various signals retrieved from modern,
      unobtrusive devices in an efficient signal abstraction framework. The signals
      include PIR motion sensors that record patient movement in the home,
      physiological signals and also patient responses in various tests performed on
      the GUI of the central home unit. We have developed and tested the prototype
      system with promising results.

PMID- 21893833
TI  - Virtual TeleRehab: a case study.
AB  - We examined the efficacy of a remotely based occupational therapy intervention. A
      40-year-old woman who suffered a stroke participated in a telerehabilitation
      program. The intervention method is based on virtual reality gaming to enhance
      the training experience and to facilitate the relearning processes. The results
      indicate that Virtual TeleRehab is an effective method for motivational,
      economical, and practical reasons by combining game-based rehabilitation in the
      home with weekly distance meetings.

PMID- 21893834
TI  - Patient empowerment by increasing information accessibility in a telecare system.
AB  - Patient empowerment is important in order to increase the quality of the medical
      care and the life quality of the patients. In this respect, the paper describes
      how a telecare system can become more "friendly" with the assisted persons
      (elderly people or post-discharged patients) due to a specific feature addressing
      the patient access to information from medical texts. The according service is
      part of the server of a tele-care/tele-assistance system (TELEASIS) and adapts
      the medical text to "patient" lay person language, contributing in this respect
      to the patient empowerment process. This component is based on an original
      terminology interpretation engine which is being briefly described in this paper.
      The TELEASIS system has a specific interface dedicated to medical personnel
      allowing the addition and assignment of medical text to patients or group of
      patients, which can be later accessed by the patients adapted to a patient
      friendly language. The medial texts are saved on a central medical information
      database which contains different content formats (text, multimedia, videos). As
      a conclusion, the adapted information available for the assisted persons and the
      communication channels established in the system increase the possibility of
      patients being better informed on their health status.

PMID- 21893835
TI  - A standard based approach for biomedical knowledge representation.
AB  - The new generation of health information standards, where the syntax and
      semantics of the content is explicitly formalized, allows for interoperability in
      healthcare scenarios and analysis in clinical research settings. Studies
      involving clinical and genomic data include accumulating knowledge as
      relationships between genotypic and phenotypic information as well as
      associations within the genomic and clinical worlds. Some involve analysis
      results targeted at a specific disease; others are of a predictive nature
      specific to a patient and may be used by decision support applications.
      Representing knowledge is as important as representing data since data is more
      useful when coupled with relevant knowledge. Any further analysis and cross
      research collaboration would benefit from persisting knowledge and data in a
      unified way. This paper describes a methodology used in Hypergenes, an EC FP7
      project targeting Essential Hypertension, which captures data and knowledge using
      standards such as HL7 CDA and Clinical Genomics, aligned with the CEN EHR 13606
      specification. We demonstrate the benefits of such an approach for clinical
      research as well as in healthcare oriented scenarios.

PMID- 21893836
TI  - Ontology-based framework for electronic health records interoperability.
AB  - The use of Electronic Health Records (EHR) is wide spread in healthcare. One of
      the most challenging tasks for EHR systems is to achieve computable semantic
      interoperability. To address EHR interoperability, a number of standardization
      efforts are progressing, however these standards are either incomplete in terms
      of functionality or lacking specification of precise meaning of underlying data.
      This paper describes an interoperable EHR framework that uses an ontology-based
      approach to facilitate exchange of information and knowledge among EHR. Based on
      the proposed framework, an interoperability scenario between a Personal Health
      Record System, an EHR and a Laboratory System is described.

PMID- 21893837
TI  - Ontology-based knowledge management for personalized adverse drug events
      detection.
AB  - Since Adverse Drug Event (ADE) has become a leading cause of death around the
      world, there arises high demand for helping clinicians or patients to identify
      possible hazards from drug effects. Motivated by this, we present a personalized
      ADE detection system, with the focus on applying ontology-based knowledge
      management techniques to enhance ADE detection services. The development of
      electronic health records makes it possible to automate the personalized ADE
      detection, i.e., to take patient clinical conditions into account during ADE
      detection. Specifically, we define the ADE ontology to uniformly manage the ADE
      knowledge from multiple sources. We take advantage of the rich semantics from the
      terminology SNOMED-CT and apply it to ADE detection via the semantic query and
      reasoning.

PMID- 21893838
TI  - A formal analysis of HL7 version 2.x.
AB  - Working interoperability not only requires harmonized system's architectures, but
      also the same interpretation of technical specifications in order to guide the
      development processes. But sometimes a specification has not made the underlying
      model explicit which would enable a coherent understanding. This paper analyses
      the structures of the HL7 Version 2.x communication standard's family and
      presents an UML class diagram for it.

PMID- 21893839
TI  - Simplifying HL7 Version 3 messages.
AB  - HL7 Version 3 offers a semantically robust method for healthcare interoperability
      but has been criticized as overly complex to implement. This paper reviews
      initiatives to simplify HL7 Version 3 messaging and presents a novel approach
      based on semantic mapping. Based on user-defined definitions, precise transforms
      between simple and full messages are automatically generated. Systems can be
      interfaced with the simple messages and achieve interoperability with full
      Version 3 messages through the transforms. This reduces the costs of HL7
      interfacing and will encourage better uptake of HL7 Version 3 and CDA.

PMID- 21893840
TI  - Creating an ontology driven rules base for an expert system for medical
      diagnosis.
AB  - Expert systems of the 1980s have failed on the difficulties of maintaining large
      rule bases. The current work proposes a method to achieve and maintain rule bases
      grounded on ontologies (like NCIT). The process described here for an expert
      system on plasma cell disorder encompasses extraction of a sub-ontology and
      automatic and comprehensive generation of production rules. The creation of rules
      is not based directly on classes, but on individuals (instances). Instances can
      be considered as prototypes of diseases formally defined by "destrictions" in the
      ontology. Thus, it is possible to use this process to make diagnoses of diseases.
      The perspectives of this work are considered: the process described with an
      ontology formalized in OWL1 can be extended by using an ontology in OWL2 and
      allow reasoning about numerical data in addition to symbolic data.

PMID- 21893841
TI  - A methodology and supply chain management inspired reference ontology for
      modeling healthcare teams.
AB  - Numerous studies and strategic plans are advocating more team based healthcare
      delivery that is facilitated by information and communication technologies
      (ICTs). However before we can design ICTs to support teams we need a solid
      conceptual model of team processes and a methodology for using such a model in
      healthcare settings. This paper draws upon success in the supply chain management
      domain to develop a reference ontology of healthcare teams and a methodology for
      modeling teams to instantiate the ontology in specific settings. This research
      can help us understand how teams function and how we can design ICTs to support
      teams.

PMID- 21893842
TI  - Supporting openEHR Java desktop application developers.
AB  - The openEHR community suggests that an appropriate approach for creating a
      graphical user interface for an openEHR-based application is to generate forms
      from the underlying archetypes and templates. However, current generation
      techniques are not mature enough to be able to produce high quality interfaces
      with good usability. Therefore, developing efficient ways to combine manually
      designed and developed interfaces to openEHR backends is an interesting
      alternative. In this study, a framework for binding a pre-designed graphical user
      interface to an openEHR-based backend is proposed. The proposed framework
      contributes to the set of options available for developers. In particular we
      believe that the approach of combining user interface components with an openEHR
      backend in the proposed way might be useful in situations where the quality of
      the user interface is essential and for creating small scale and experimental
      systems.

PMID- 21893843
TI  - Large scale healthcare data integration and analysis using the semantic web.
AB  - Healthcare data interoperability can only be achieved when the semantics of the
      content is well defined and consistently implemented across heterogeneous data
      sources. Achieving these objectives of interoperability requires the
      collaboration of experts from several domains. This paper describes tooling that
      integrates Semantic Web technologies with common tools to facilitate cross-domain
      collaborative development for the purposes of data interoperability. Our approach
      is divided into stages of data harmonization and representation, model
      transformation, and instance generation. We applied our approach on Hypergenes,
      an EU funded project, where we use our method to the Essential Hypertension
      disease model using a CDA template. Our domain expert partners include clinical
      providers, clinical domain researchers, healthcare information technology
      experts, and a variety of clinical data consumers. We show that bringing Semantic
      Web technologies into the healthcare interoperability toolkit increases
      opportunities for beneficial collaboration thus improving patient care and
      clinical research outcomes.

PMID- 21893844
TI  - ACGT: advancing clinico-genomic trials on cancer - four years of experience.
AB  - The challenges regarding seamless integration of distributed, heterogeneous and
      multilevel data arising in the context of contemporary, post-genomic clinical
      trials cannot be effectively addressed with current methodologies. An urgent need
      exists to access data in a uniform manner, to share information among different
      clinical and research centers, and to store data in secure repositories assuring
      the privacy of patients. Advancing Clinico-Genomic Trials (ACGT) was a European
      Commission funded Integrated Project that aimed at providing tools and methods to
      enhance the efficiency of clinical trials in the -omics era. The project, now
      completed after four years of work, involved the development of both a set of
      methodological approaches as well as tools and services and its testing in the
      context of real-world clinico-genomic scenarios. This paper describes the main
      experiences using the ACGT platform and its tools within one such scenario and
      highlights the very promising results obtained.

PMID- 21893845
TI  - Architectural approach for providing relations in biomedical terminologies and
      ontologies.
AB  - The representation of multiple relations is one of the main criteria of
      ontologies. In formalizing both ontologies and terminologies in biomedicine
      relations are used to code axioms for the classes of the ontology. However, a
      huge number of relations represented in medical ontologies and terminologies are
      derived from language and formal definition is omitted. We present a strategy
      based on an architectural approach to facility formal analysis of relations for
      use in ontology systems in biomedicine and in general.

PMID- 21893846
TI  - Integration of classifications and terminologies in Metadata registries based on
      ISO/IEC 11179.
AB  - Empirical medical research needs services for the maintenance of item
      collections. We evaluated the appropriateness of ISO/IEC 11179 "Information
      technology - Metadata Registries (MDR)" part 3 "Registry Metamodel and basic
      attributes" for a national MDR. In particular, possibilities of including
      classifications and terminologies (summarized as vocabularies) using the
      metamodel of this standard were assessed. The hierarchical structure of
      classifications and terminologies could be mapped easily to ISO's metamodel. The
      Classification Markup Language (ClaML) is attractive as interface standard for
      the import of classifications into the MDR. The correct linkage between data
      elements and vocabularies remained unclear however. An extension of the ISO 11179
      metamodel might be necessary to satisfy the predefined needs of a national MDR.

PMID- 21893847
TI  - Development of a new international classification of health interventions based
      on an ontology framework.
AB  - : The WHO International Classification of Diseases is used in many national
      applications to plan, manage and fund through case mix health care systems and
      allows international comparisons of the performance of these systems. There is no
      such measuring tool for health interventions or procedures. To fulfil this
      requirement the WHO-FIC Network recommended in 2006 to develop an International
      Classification of Health Interventions (ICHI). This initiative is aimed to
      harmonise the existing national classifications and to provide a basic system for
      the countries which have not developed their own classification systems. It is
      based on the CEN/ISO ontology framework standard named Categorial Structure
      defined from a non formal bottom up ontology approach. The process of populating
      the framework is ongoing to start from a common model structure encompassing the
      ICD 9CM Volume 3 granularity.

PMID- 21893848
TI  - The revision of the Korean classifications of health interventions based on the
      proposed ICHI semantic model and lessons learned.
AB  - The Korean Medical Association and the Health Information Review Agency have
      decided to re-engineer the different Korean coding systems of health
      interventions based on a proposed ontology framework defined in 2010 for the
      prospective International Classification of Health Interventions (ICHI). The
      authors present the interim report of the project focused on this model: 5,338
      procedures of the Korean version of ICD9-CM 5,150 procedures covered by Korean
      health insurance and 6,619 uncovered procedure labels were processed with the
      participation of 8 coders and 310 medical doctors. As of 28<sup>th</sup> January
      61.8% of data was processed. The ontology framework model itself was not enough
      to represent all the labels when the preliminary data from obstetrics and
      gynecology was explored. However, when modified with 7 notations, it was possible
      to assign each label of ICD 9 CM Volume 3 and 30 % to 57 % of specific Korean
      interventions to the semantic model.

PMID- 21893849
TI  - Web-based collaboration for terminology application: ICNP C-space.
AB  - The purpose of this paper is to describe the ongoing evolution of a nursing
      terminology that involves users in all aspects of the terminology lifecycle. A
      terminology will not succeed until and unless it benefits users and contributes
      to improved client outcomes at the point of care. Since the release of
      ICNP(r)Version 1 in 2005, users have been necessary partners in research and
      development, dissemination and education, and, to some extent, in terminology
      maintenance and operations. ICNP C-Space was launched in 2008 as a platform for
      collaboration among users and the ICNP team. C-Space applications include, but
      are not limited to, the ICNP browser, a multi-lingual browser, catalogue
      development pages, and group discussion pages. Future uses may include work
      related to ICN research and networks. C-Space adds value to ICNP, ICN, and
      nursing worldwide by ensuring that terminology users can contribute their
      expertise to finding workable solutions and developing important products related
      to ICNP.

PMID- 21893850
TI  - Mapping medical records of gastrectomy patients to SNOMED CT.
AB  - The purpose of this study is to explore the ability of SNOMED CT to represent
      narrative statements of medical records. Narrative medical records of 281
      hospitalization days of 36 patients with Gastrectomy were decomposed into single
      meaning statements, and these single-meaning statements were combined into unique
      statements by removing semantically redundant statements. Concepts from the
      statements describing patients' problems and treatments were mapped to SNOMED CT
      concepts. A total 4717 single-meaning statements were collected and these single
      meaning statements were combined into 858 unique statements. Out of 677 unique
      statements describing patients' problems and treatments, about 85.5% statements
      were fully mapped to SNOMED CT. The rest of the statements were partially mapped.
      This mapping result implies that physicians' narrative medical records can be
      structured and used for an electronic medical record system.

PMID- 21893851
TI  - Terminology for the description of the diagnostic studies in the field of EBM.
AB  - Diagnostic systematic reviews is a relatively new area within the Evidence-Based
      Medicine (EBM). Their indexing in Pubmed is not precise, which complicates their
      detection when a systematic review is to be realized. In order to provide an
      assistance in the selection of relevant studies, we propose to develop a
      terminology describing this area and the organization of its terms. The
      terminology is built with a bottom-up approach. It contains 255 terms organized
      into five hierarchical levels. Only a small proportion of these terms (13%) are
      already registered in MeSH. This terminology will be exploited in a dedicated web
      service as a main tool for the detection of relevant diagnostic studies.

PMID- 21893852
TI  - Representing knowledge, data and concepts for EHRS using DCM.
AB  - With the move towards next generations of Electronic Health Record Systems
      (EHRS), the focus changes from administrative and data retrieval and data entry
      system capabilities towards clinical functions. The representation of the
      clinical knowledge and evidence base into EHRS becomes an important asset for
      health care, with its own challenges. Clinician's do want EHRS support but do not
      want to standardize care, they do want unified terminology and structured data
      entry but also free text. In addition, information modelers challenge each other
      for the best solution, and care pathways and other workflows seem to differ for
      each situation. Such diverging approaches add complexity to the already difficult
      situation around Information Technology in health care, the EHRS in particular.
      This paper argues that a change is necessary to adopt Detailed Clinical Modeling
      as a method to organize clinical knowledge, represent concepts and define data in
      such a manner that it allows for semantics to be exchanged without being trapped
      in a specific technology. DCM help to fulfill the requirements for the enter data
      once, reuse multiple times paradigm for EHRS.

PMID- 21893853
TI  - Ontology-based automatic generation of computerized cognitive exercises.
AB  - Computer-based approaches can add great value to the traditional paper-based
      approaches for cognitive rehabilitation. The management of a big amount of
      stimuli and the use of multimedia features permits to improve the patient's
      involvement and to reuse and recombine them to create new exercises, whose
      difficulty level should be adapted to the patient's performance. This work
      proposes an ontological organization of the stimuli, to support the automatic
      generation of new exercises, tailored on the patient's preferences and skills,
      and its integration into a commercial cognitive rehabilitation tool. The
      possibilities offered by this approach are presented with the help of real
      examples.

PMID- 21893854
TI  - Creating a magnetic resonance imaging ontology.
AB  - The goal of this work is to build an ontology of Magnetic Resonance Imaging. The
      MRI domain has been analysed regarding MRI simulators and the DICOM standard. Tow
      MRI simulators have been analysed: JEMRIS, which is developed in XML and C++, has
      a hierarchical organisation and SIMRI, which is developed in C, has a good
      representation of MRI physical processes. To build the ontology we have used
      Protege 4, owl2 that allows quantitative representations. The ontology has been
      validated by a reasoner (Fact++) and by a good representation of DICOM headers
      and of MRI processes. The MRI ontology would improved MRI simulators and eased
      semantic interoperability.

PMID- 21893855
TI  - Validation of the openEHR archetype library by using OWL reasoning.
AB  - Electronic Health Record architectures based on the dual model architecture use
      archetypes for representing clinical knowledge. Therefore, ensuring their
      correctness and consistency is a fundamental research goal. In this work, we
      explore how an approach based on OWL technologies can be used for such purpose.
      This method has been applied to the openEHR archetype repository, which is the
      largest available one nowadays. The results of this validation are also reported
      in this study.

PMID- 21893856
TI  - Grouping pharmacovigilance terms with semantic distance.
AB  - Pharmacovigilance is the activity related to the collection, analysis and
      prevention of adverse drug reactions (ADRs) induced by drugs or biologics.
      Besides other methods, statistical algorithms are used to detect previously
      unknown ADRs, and it was noted that groupings of ADR terms can further improve
      safety signal detection. Standardised MedDRA Queries are developed to assist
      retrieval and evaluation of MedDRA-coded ADR reports. Dependent on the context of
      their application, different SMQs show varying degrees of specificity and
      sensitivity; some appear to be over-inclusive, some might miss relevant terms.
      Moreover, several important safety topics are not yet fully covered by SMQs. The
      objective of this work is to propose an automatic method for the creation of
      groupings of terms. This method is based on the application of the semantic
      distance between MedDRA terms. Several experiments are performed, showing a
      promising precision and an acceptable recall.

PMID- 21893858
TI  - Using a logical information model-driven design process in healthcare.
AB  - A hybrid standards-based approach has been adopted in Singapore to develop a
      Logical Information Model (LIM) for healthcare information exchange. The
      Singapore LIM uses a combination of international standards, including ISO13606-1
      (a reference model for electronic health record communication), ISO21090
      (healthcare datatypes), SNOMED CT (healthcare terminology) and HL7 v2 (healthcare
      messaging). This logic-based design approach also incorporates mechanisms for
      achieving bi-directional semantic interoperability.

PMID- 21893857
TI  - The Archetype-enabled EHR system ZK-ARCHE - integrating the ISO/EN 13606 standard
      and IHE XDS profile.
AB  - The EHR system ZK-ARCHE automatically generates forms from ISO/EN 13606
      archetypes. For this purpose the archetypes are augmented with components of the
      reference model to achieve so-called "comprehensive archetypes". Data collected
      via the forms are stored in a list which associates each value with the path of
      the corresponding comprehensive archetype node coded as W3C XPath. From this list
      archetype-conformant EHR extracts can be created. The system is embedded with the
      IHE XDS profile to allow direct data exchange in an environment of distributed
      data storage.

PMID- 21893859
TI  - SNOMED CT implementation: implications of choosing clinical findings or
      observable entities.
AB  - Internationally, it is a priority to develop and implement semantically
      interoperable health information systems.[1] One required technology is the use
      of standardised clinical terminologies. The terminology, SNOMED CT, has shown
      superior coverage compared to other terminologies in multiple clinical fields.
      The aim of this paper is to analyse SNOMED CT implementation in an Electronic
      Health Record (EHR). More specifically, differences and consequences of applying
      clinical findings (CFs) as an alternative to observable entities (OEs) is
      analysed. Results show that CFs represents the content of the templates with
      better coverage, with more parent concepts and with a higher degree of fully
      defined terms than the OEs. We discuss the possibility to further evaluate the
      observable entity hierarchy to overcome a potential overlapping use of the two
      hierarchies.

PMID- 21893860
TI  - What is the coverage of SNOMED CT(r)on scientific medical corpora?
AB  - This paper reports on the results of a large scale mapping of SNOMED CT on
      scientific medical corpora. The aim is to automatically access the validity,
      reliability and coverage of the Swedish SNOMED-CT translation, the largest, most
      extensive available resource of medical terminology. The method described here is
      based on the generation of predominantly safe harbor term variants which together
      with simple linguistic processing and the already available SNOMED term content
      are mapped to large corpora. The results show that term variations are very
      frequent and this may have implication on technological applications (such as
      indexing and information retrieval, decision support systems, text mining) using
      SNOMED CT. Naive approaches to terminology mapping and indexing would critically
      affect the performance, success and results of such applications. SNOMED CT
      appears not well-suited for automatically capturing the enormous variety of
      concepts in scientific corpora (only 6,3% of all SNOMED terms could be directly
      matched to the corpus) unless extensive variant forms are generated and fuzzy and
      partial matching techniques are applied with the risk of allowing the recognition
      of a large number of false positives and spurious results.

PMID- 21893861
TI  - Assisting the translation of the CORE subset of SNOMED CT into French.
AB  - BACKGROUND: the Core Subset of SNOMED CT is part of the UMLS-Core Project
      dedicated to study problem list vocabularies. SNOMED CT is not yet translated
      into French. OBJECTIVE: to propose an automated method to assist the translation
      of the CORE Subset of SNOMED CT into French. MATERIAL: the 2009 AA versions of
      the CORE Subset of SNOMED CT and UMLS; use of four French-language terminologies
      integrated into the UMLS Metathesaurus: SNOMED International, ICD10, MedDRA, and
      MeSH. METHOD: an exact mapping completed by a close mapping between preferred
      terms of the CORE Subset of SNOMED CT and those of the four terminologies.
      RESULTS: 89% of the preferred terms of the CORE Subset of SNOMED CT are mapped
      with at least one preferred term in one of the four terminologies. DISCUSSION: if
      needed, synonymous terms could be added by the means of synonyms in the
      terminologies; the proposed method is independent from French and could be
      applied to other natural languages.

PMID- 21893862
TI  - Recording associated disorders using SNOMED CT.
AB  - Multidisciplinary communication about patients with multiple and often
      interrelated diseases is of utmost importance to guarantee high quality of care.
      In this paper we focus on storing into the electronic medical record patients'
      disorders which are associated with each other, taking into account the role of
      SNOMED CT. The objectives of this paper are to design and discuss possibilities
      to appropriately record the associations between two disorders as defined in
      SNOMED CT and to get insight into the use of the relationship "associated with"
      in SNOMED CT and its consequences for data reuse. Our study showed that textual
      and concept-based reproducible recording of reusable data is hampered due to
      incorrect or incomplete modeling of associations between disorders in SNOMED CT.
      A possible solution for this is to record constituting characteristics of
      concepts directly into the record, instead of only being represented in the
      terminology. Further research on binding of information models and terminologies
      is needed.

PMID- 21893863
TI  - SNOMED CT's RF2: Is the future bright?
AB  - SNOMED CT's new RF2 format is said to come with features for better configuration
      management of the SNOMED vocabulary, thereby accommodating evolving requirements
      without the need for further fundamental change in the foreseeable future.
      Although the available documentation is not yet convincing enough to support this
      claim, the newly introduced Model Component hierarchy and associated reference
      set mechanism seem to hold real promise of being able to deal successfully with a
      number of ontological issues that have been discussed in the recent literature.
      Backed up by a study of the old and new format and of the relevant literature and
      documentation, three recommendations are presented that would free SNOMED CT from
      use-mention confusions, unclear referencing of real-world entities and
      uninformative reasons for change in a way that does not force SNOMED CT to take a
      specific philosophical or ontological position.

PMID- 21893864
TI  - Serious adverse event reporting in a medical device information system.
AB  - The paper describes the design of a module that manages Serious Adverse Events
      (SAEs) reporting within a Clinical investigation on Medical devices. This module
      is integrated in a Medical Device Information System (MEDIS) that collects data
      and documents exchanged between applicants and the National Competent Authority
      during the clinical investigation lifecycle. To improve information sharing among
      different stakeholders and systems MEDIS design and developed were based on the
      HL7 v.3 standards. The paper provides a conceptual model on SAEs based on HL7 RIM
      that underlines Medical Device characteristics.

PMID- 21893865
TI  - Metadata - an international standard for clinical knowledge resources.
AB  - This paper describes a new European and International standard, ISO 13119 Health
      informatics - Clinical knowledge resources - Metadata that is intended for both
      health professionals and patients/citizens. This standard aims to facilitate two
      issues: 1) How to find relevant documents that are appropriate for the reader and
      situation and 2) How to ensure that the found knowledge documents have a
      sufficient or at least declared quality management? Example of use is provided
      from the European Centre for Disease Control and Prevention.

PMID- 21893866
TI  - Comparing existing national and international classification systems of surgical
      procedures with the CEN/ISO 1828 ontology framework standard.
AB  - Among different standardization strategies for biomedical terminologies the
      European Standard Body CEN TC 251 followed by ISO TC 215 have stated that it was
      not possible to convince the different European or international member states
      using different national languages to agree on a reference clinical terminology
      or to standardize a detailed language independent biomedical ontology. Since 1990
      they have developed since an approach named the Categorial Structure that
      standardises only the terminologies' model structure. The methodology for the
      Categorial Structure development and a comparison of the different existing
      classification systems based on this ontology framework is presented as a step
      towards increased interoperability between biomedical terminologies through
      conformity to a minimum set of ontological requirements.

PMID- 21893867
TI  - Model driven development of clinical information sytems using openEHR.
AB  - openEHR and the recent international standard (ISO 13606) defined a model driven
      software development methodology for health information systems. However there is
      little evidence in the literature describing implementation; especially for
      desktop clinical applications. This paper presents an implementation pathway
      using .Net/C# technology for Microsoft Windows desktop platforms. An endoscopy
      reporting application driven by openEHR Archetypes and Templates has been
      developed. A set of novel GUI directives has been defined and presented which
      guides the automatic graphical user interface generator to render widgets
      properly. We also reveal the development steps and important design decisions;
      from modelling to the final software product. This might provide guidance for
      other developers and form evidence required for the adoption of these standards
      for vendors and national programs alike.

PMID- 21893868
TI  - A metadata-based patient register for cooperative clinical research: a case study
      in acute myeloid leukemia.
AB  - In many medical indications clinical research is organized within study groups
      which provide and maintain the clinical infrastructure for their randomized
      clinical trials. Each group also manages a data center where high quality
      databases store the study specific individual patient data. Sharing this data
      between study groups is not straightforward. Therefore, a concept is needed which
      allows to represent a detailed overview on the information available across the
      cooperating groups. We propose a metadata based patient register and describe a
      first prototype. It provides information about available patient data sets to
      interested research partners while the typical register approach only collects a
      predefined limited core data set. This register implementation enables
      cooperative groups to allocate clinical data for future research projects in
      distributed data sources beyond the restrictions of core data sets. Additionally,
      it supports the research network in communication and data standardization and
      complies with a governance structure which is compatible with ethical aspects,
      privacy protection, and patient rights.

PMID- 21893869
TI  - De-identifying an EHR database - anonymity, correctness and readability of the
      medical record.
AB  - Electronic health records (EHR) contain a large amount of structured data and
      free text. Exploring and sharing clinical data can improve healthcare and
      facilitate the development of medical software. However, revealing confidential
      information is against ethical principles and laws. We de-identified a Danish EHR
      database with 437,164 patients. The goal was to generate a version with real
      medical records, but related to artificial persons. We developed a de
      identification algorithm that uses lists of named entities, simple language
      analysis, and special rules. Our algorithm consists of 3 steps: collect lists of
      identifiers from the database and external resources, define a replacement for
      each identifier, and replace identifiers in structured data and free text. Some
      patient records could not be safely de-identified, so the de-identified database
      has 323,122 patient records with an acceptable degree of anonymity, readability
      and correctness (F-measure of 95%). The algorithm has to be adjusted for each
      culture, language and database.

PMID- 21893870
TI  - Service oriented data integration for a biomedical research network.
AB  - In biomedical research, a variety of data like clinical, genetic, expression of
      coding or non-coding ribonucleic acid (RNA) transcripts, or proteomic data are
      processed to gain new insights into diseases and therapies. In transregional
      research networks, geographically distributed projects work on comparable
      research questions with data from different resources and in different formats.
      Providing an information platform that integrates the data of the projects can
      enable cross-project analysis and provides an overview of available data and
      resources (tissue, blood, etc.). For a German liver cancer research network
      consisting of 22 individual projects, we develop the integrated information
      platform pelican - platform enhancing liver cancer networked research. In our
      generic approach, data are made available to the research network by standardized
      data services based on technologies provided by the cancer Biomedical Informatics
      Grid (caBIG). It has shown that publishing service metadata in a corresponding
      repository is a major prerequisite for automated discovery, integration, and
      conversion of data records and data services. We identified data confidentiality
      and intellectual property considerations as major challenges while establishing
      such an integrated information platform. As a first result we implemented a
      working prototype to validate our approach.

PMID- 21893871
TI  - Single source information systems can improve data completeness in clinical
      studies: an example from nuclear medicine.
AB  - Data for clinical documentation and medical research are usually managed in
      separate systems. A documentation system for myocardial scintigraphy (SPECT/CT
      data) was developed, implemented and assessed in order to integrate clinical and
      research documentation. This paper presents concept, implementation and results
      regarding data completeness of this single source information system.
      Completeness of documentation increased highly significantly (p<0.0001) after
      implementation of this system.

PMID- 21893872
TI  - Reporting qualitative research in health informatics: REQ-HI recommendations.
AB  - To develop a set of recommendations for authors of qualitative studies in the
      field of health informatics, we conducted an extensive literature search and also
      manually checked major journals in the field of biomedical informatics and
      qualitative research looking for papers, checklists, and guidelines pertaining to
      assessing and reporting of qualitative studies. We synthesized the found criteria
      to develop an initial set of reporting recommendations that are particularly
      relevant to qualitative studies of health information technology systems. This
      paper presents a preliminary version of these recommendations. We are planning to
      refine and revise this version using comments and suggestions of experts in
      evaluation of health informatics applications and publish a detailed set of
      recommendations.

PMID- 21893873
TI  - Cell seeding of tissue engineering scaffolds studied by Monte Carlo simulations.
AB  - Tissue engineering (TE) aims at building multicellular structures in the
      laboratory in order to regenerate, to repair or replace damaged tissues. In a
      well-established approach to TE, cells are cultured on a biocompatible porous
      structure, called scaffold. Cell seeding of scaffolds is an important first step.
      Here we study conditions that assure a uniform and rapid distribution of cells
      within the scaffold. The movement of cells has been simulated using the
      Metropolis Monte Carlo method, based on the principle that cellular system tends
      to achieve the minimum energy state. For different values of the model
      parameters, evolution of the cells' centre of mass is followed, which reflects
      the distribution of cells in the system. For comparison with experimental data,
      the concentration of the cells in the suspension adjacent to the scaffold is also
      monitored. Simulations of cell seeding are useful for testing different
      experimental conditions, which in practice would be very expensive and hard to
      perform. The computational methods presented here may be extended to model cell
      proliferation, cell death and scaffold degradation.

PMID- 21893874
TI  - The ONCO-I2b2 project: integrating biobank information and clinical data to
      support translational research in oncology.
AB  - The University of Pavia and the IRCCS Fondazione Salvatore Maugeri of Pavia
      (FSM), has recently started an IT initiative to support clinical research in
      oncology, called ONCO-i2b2. ONCO-i2b2, funded by the Lombardia region, grounds on
      the software developed by the Informatics for Integrating Biology and the Bedside
      (i2b2) NIH project. Using i2b2 and new software modules purposely designed, data
      coming from multiple sources are integrated and jointly queried. The core of the
      integration process stands in retrieving and merging data from the biobank
      management software and from the FSM hospital information system. The integration
      process is based on a ontology of the problem domain and on open-source software
      integration modules. A Natural Language Processing module has been implemented,
      too. This module automatically extracts clinical information of oncology patients
      from unstructured medical records. The system currently manages more than two
      thousands patients and will be further implemented and improved in the next two
      years.

PMID- 21893875
TI  - IT infrastructure components to support clinical care and translational research
      projects in a comprehensive cancer center.
AB  - This paper presents the concept of an integrated IT infrastructure framework
      established at the comprehensive cancer center at the University Hospital
      Erlangen. The framework is based on the single source concept where data from the
      electronic medical record are reused for clinical and translational research
      projects. The applicability of the approach is illustrated by two case studies
      from colon cancer and prostate cancer research projects.

PMID- 21893876
TI  - Using a robotic arm to assess the variability of motion sensors.
AB  - For the assessment of physical activity, motion sensors have become increasingly
      important. To assure a high accuracy of the generated sensor data, the
      measurement error of these devices needs to be determined. Sensor variability has
      been assessed with various types of mechanical shakers. We conducted a small
      feasibility study to explore if a programmable robotic arm can be a suitable tool
      for the assessment of variability between different accelerometers (inter-device
      variability). We compared the output of the accelerometers GT1M and GT3X (both
      ActiGraph) and RT3 (Stayhealthy) for two different movement sequences.

PMID- 21893877
TI  - The single source architecture x4T to connect medical documentation and clinical
      research.
AB  - Clinical trials often require large and redundant documentation efforts, because
      information systems in patient care and research are separated. In two clinical
      trials we have assessed the number of study items available in the clinical
      information system for re-use in clinical research. We have analysed common
      standards such as HL7, IHE RFD and CDISC ODM, regulatory constraints and the
      documentation process. Based on this analysis we have designed and implemented an
      architecture for an integrated clinical trial documentation workflow. Key aspects
      are the re-use of existing medical routine data and the integration into current
      documentation workflows.

PMID- 21893878
TI  - Information technology solutions to support translational research on inherited
      cardiomyopathies.
AB  - The INHERITANCE project, funded by the European Commission, is aimed at studying
      genetic or inherited Dilated cardiomyopathies (DCM) and at understanding the
      impact and management of the condition within families that suffer from heart
      conditions that are caused by DCMs. The project is supported by a number of
      advanced biomedical informatics tools, including data warehousing, automated
      literature search and decision support. The paper describes the design of these
      tools and the current status of implementation.

PMID- 21893879
TI  - Emerging approaches to usability evaluation of health information systems:
      towards in-situ analysis of complex healthcare systems and environments.
AB  - The effective evaluation of health information technology (HIT) is currently a
      major challenge. It is essential that applications we develop are usable, meet
      user information needs and are shown to be safe. Furthermore, to provide
      appropriate feedback to designers of systems new methods for both formative and
      summative evaluation are needed as applications become more complex and
      distributed. To ensure system usability a variety of methods have emerged from
      the area of usability engineering that have been adapted to healthcare. The
      authors have applied methods of usability engineering, working with hospitals and
      other healthcare organizations designing and evaluating a range of HIT
      applications. We describe how our approach to doing portable low-cost usability
      testing has evolved to the use of clinical simulations conducted in-situ, within
      real hospital and clinical units to rapidly evaluate the usability and safety of
      healthcare information systems both before and after system release. We discuss
      how this approach was extended to development of methods for conducting in-situ
      clinical simulations in a range of clinical settings.

PMID- 21893880
TI  - Contextualization of automatic alerts during electronic prescription:
      researchers' and users' opinions on useful context factors.
AB  - Computerized Physician Order Entry (CPOE) Systems can reduce the number of
      medication errors and Adverse Drug Events (ADEs). However, studies have shown
      that users often override alerts, as they feel these are too unspecific for the
      given patient context. It is unclear, however, how alerts could be
      contextualized, that is adapted to the clinical context. Based on a literature
      search, we developed a list of 20 possible context factors. We asked 69
      international CPOE researchers and 120 physicians from four hospitals in two
      countries to judge the usefulness of each factor. Researchers judged the
      following factors as most important: 1.) Severity of the effect, 2.) Clinical
      status of the patient, 3.) Probability of occurrence, 4.) Risk factors of the
      patient, 5.) Strength of evidence. Physicians judged the following factors as
      most important: Severity of the effect, clinical status of the patients,
      complexity of the case, and class of drug. These top-ranked context factors could
      be used to re-design the way alerts are presented in CPOE systems, to increase
      sensitivity of alerts, to reduce overriding rates, and to improve medication
      safety.

PMID- 21893881
TI  - Reducing clinicians' cognitive workload by system redesign; a pre-post think
      aloud usability study.
AB  - Interactive Health Information systems are often considered cognitively complex
      by their users, leading to high cognitive burden and increased workload. This
      paper explores if Think Aloud usability testing provides valuable input to
      effectively redesign a web-based Data Query Tool in Intensive Care and to reduce
      physicians' cognitive workload during system interaction. Pre and post redesign
      usability testing demonstrated a major reduction in the cognitive task workload
      after redesign of the tool. Classification of revealed usability problems by
      means of the User Action Framework pointed out that usability problems related to
      the cognitively planning of actions by system users foremost affected cognitive
      task workload. This result may support Health Information system (re)design
      efforts on how to tackle the system's cognitive complexity and in so doing
      improve on its usability.

PMID- 21893882
TI  - Impact of alert specifications on clinicians' adherence.
AB  - Computerized alerts provided by health care information systems have been shown
      to enhance clinical practice. However, clinicians still override more than half
      of the alerts. This indicates that certain aspects of alerts need improvement to
      fulfill their purpose of supporting clinicians in decision making. This paper
      reports on a systematic review on studies evaluating alert specifications and
      their impact on clinicians' alert adherence. The review revealed that use of
      colors and icons to distinguish different alert severity levels and presenting
      high severity alerts in an interruptive fashion increases clinicians adherence to
      alert recommendations. Alert message contents that lack clinical importance or
      provide incorrect texts increase alert non-adherence. Few studies have yet
      focused on the impact of alert specifications on clinicians' adherence. A
      research agenda is needed on alert specifications and their impact on clinicians'
      adherence in order to develop alerts that truly support clinician decision
      making.

PMID- 21893883
TI  - Medication decision-making on hospital ward-rounds.
AB  - This research explored the decision-making process of selecting medicines for
      prescription on hospital ward-rounds. We aimed to determine when and with whom
      medications were discussed, and in particular, whether shared decision making
      (SDM) occurred on ward-rounds. As a low level of computerized decision support
      was in place in the hospital at the time, we also examined whether the decision
      support aided in any medication discussions. Fourteen specialty teams (46
      doctors) were shadowed by the investigator while on ward-rounds and all verbal
      communication about medications was noted. Most medication discussions took place
      away from the patient bedside and the majority took place between two or more
      doctors. While a great deal of doctor-patient communication regarding medications
      took place on ward-rounds, very little of this comprised SDM. More frequently,
      doctors informed patients of the medications they would be or were currently
      taking. The computerized decision support had little impact on treatment decision
      making. While the value of SDM is often acknowledged in the literature, it
      appears to be rarely practiced on hospital ward-rounds.

PMID- 21893884
TI  - A qualitative analysis of prescription activity and alert usage in a computerized
      physician order entry system.
AB  - Medical alerts in CPOE are overridden in most cases. The need for alerting
      systems that are better adapted to physicians' needs and work processes is
      recognized. Our study aims to shed some light on how medical alerts are used and
      how they are integrated in the work process. Work analysis and interviews
      resulted in a hierarchical task analysis of prescription during ward rounds at
      the University Hospitals of Geneva. The results indicate that non-modal medical
      alerts are appreciated as an "insurance" for drugs that are out of the routine
      set. In the case of drugs that are often prescribed, alerts are ignored as
      physicians feel comfortable prescribing them. Non-interrupting alerts do not
      cognitively overcharge physicians, but the question is how to display the
      numerous alerts so that they are easily accessible when needed. Further,
      inexperienced physicians lack a mental representation of what evaluations the
      system is doing with the prescriptions and when alerts are triggered. This may
      lead to lack of trust or overconfidence, both of them potentially harmful.

PMID- 21893885
TI  - Combining usability testing with eye-tracking technology: evaluation of a
      visualization support for antibiotic use in intensive care.
AB  - This research work is an explorative study to measure efficiency, effectiveness
      and user satisfaction of a prototype called Infobiotika aiming to support
      antibiotic use in intensive care. The evaluation was performed by combining
      traditional usability testing with eye-tracking technology. The test was
      conducted with eight intensive care physicians whereof four specialists and four
      residents. During three test phases participants were asked to perform three
      types of tasks, namely navigational, clinical and tasks to measure the learning
      effect after 3-5 minutes free exploring time. A post-test questionnaire was used
      to explore user satisfaction. Based on the results and overall observations,
      Infobiotika seems to be effective and efficient in terms of supporting navigation
      and also a learnable product for intensive care physicians fulfilling their need
      to get an accurate overview of a patient status quickly. Applying eye-tracking
      technology during usability testing has shown to be a valuable complement to
      traditional methods that revealed many unexpected issues in terms of navigation
      and contributed a supplementary understanding about design problems and user
      performance.

PMID- 21893886
TI  - Design of a mobile, safety-critical in-patient glucose management system.
AB  - Diabetes mellitus is one of the most widespread diseases in the world. People
      with diabetes usually have long stays in hospitals and need specific treatment.
      In order to support in-patient care, we designed a prototypical mobile in-patient
      glucose management system with decision support for insulin dosing. In this paper
      we discuss the engineering process and the lessons learned from the iterative
      design and development phases of the prototype. We followed a user-centered
      development process, including real-life usability testing from the outset. Paper
      mock-ups in particular proved to be very valuable in gaining insight into the
      workflows and processes, with the result that user interfaces could be designed
      exactly to the specific needs of the hospital personnel in their daily routine.

PMID- 21893887
TI  - Facilitating the iterative design of informatics tools to advance the science of
      autism.
AB  - This paper describes a usability evaluation study of an innovative first
      generation system (Data Dig) designed to retrieve phenotypic data from the large
      SFARI data set of 2700 families each of which has one child affected with autism
      spectrum disorder. The usability methods included a cognitive walkthrough and
      usability testing. Although the subjects were able to learn to use the system,
      more than 50 usability problems of varying severity were noted. The problems with
      the greatest frequency resulted from users being unable to understand meanings of
      variables, filter categories correctly, use the Boolean filter, and correctly
      interpret the feedback provided by the system. Subjects had difficulty forming a
      mental model of the organizational system underlying the database. This precluded
      them from making informed navigation choices while formulating queries. Clinical
      research informatics is a new and immensely promising discipline. However in its
      nascent stage, it lacks a stable interaction paradigm to support a range of users
      on pertinent tasks. This presents great opportunity for researchers to further
      this science by harnessing the powers of user-centered iterative design.

PMID- 21893888
TI  - Evaluation of computer usage in healthcare among private practitioners of NCT
      Delhi.
AB  - OBJECTIVES: 1. To evaluate the usage and the knowledge of computers and
      Information and Communication Technology in health care delivery by private
      practitioners. 2. To understand the determinants of computer usage by them.
      METHODS: A cross sectional study was conducted among the private practitioners
      practising in three districts of NCT of Delhi between November 2007 and December
      2008 by stratified random sampling method, where knowledge and usage of computers
      in health care and determinants of usage of computer was evaluated in them by a
      pre-coded semi open ended questionnaire. RESULTS: About 77% of the practitioners
      reported to have a computer and had the accessibility to internet. Computer
      availability and internet accessibility was highest among super speciality
      practitioners. Practitioners who attended a computer course were 13.8 times [OR:
      13.8 (7.3 - 25.8)] more likely to have installed an EHR in the clinic. Technical
      related issues were the major perceived barrier in installing a computer in the
      clinic. CONCLUSION: Practice speciality, previous attendance of a computer
      course, age of started using a computer influenced the knowledge about computers.
      Speciality of the practice, presence of a computer professional and gender were
      the determinants of usage of computer.

PMID- 21893889
TI  - Contextual inquiry method for user-centred clinical IT system design.
AB  - Little can be found in the literature about the applicability of field study
      methods, particularly contextual inquiry, in the health informatics field. This
      paper aims to inform and promote the use of contextual inquiry for user-oriented
      design of clinical information technology (IT) systems. The paper describes how
      the method was applied in two empirical studies to gather data about end-users'
      needs, as well as the use and usability of dictation solutions and electronic
      nursing documentation systems from the viewpoint of their end-users' in real
      working surroundings. Experience indicates that, compared to typical usability
      evaluation methods, contextual inquiry may provide valuable support for user
      centred design activities: the method is suitable for increasing researchers'
      understanding of clinical practices, contexts of work, and end-users' interaction
      with numerous IT systems. However, in clinical settings there are special
      challenges related to recording and privacy issues, a wide variety of clinical
      practices and contexts of technology usage, as well as the hectic nature of
      clinical work.

PMID- 21893890
TI  - A Method to Measure the Reduction of CO2 Emissions in E-Health Applications.
AB  - Climate change is perhaps the topmost challenge of our time. To prevent climate
      change from severely impacting almost every facet of life on the planet,
      scientific consensus points to a need to reduce the emissions of greenhouse gases
      (GHG), measured in terms of CO<inf>2</inf> equivalents (CO<inf>2</inf>e), by as
      much as 80 percent by 2050. So far the focus has centered on incremental
      reductions of CO<inf>2</inf> e emissions in areas in which they are highest,
      without negatively impacting the economy. But there is also a large untapped
      opportunity to drive economic growth by applying transformative solutions. In
      this paper, a method to evaluate CO<inf>2</inf>e reduction in the e-health
      applications is presented.

PMID- 21893891
TI  - Medical informatic research management in academia - the Danish setting.
AB  - The condition that the Danish universities have been subject to severe changes
      through the last decade has had huge consequences for management of research at
      the level of a discipline as Medical Informatics. The presentation pinpoints some
      of the instruments, which is on top of the management agenda in the new academic
      reality in Denmark. Performance contracts, organizational structure, general
      management, research constraints, ranking and performance issues, economy linked
      to production, ownership, and incitements are issues affecting the way research
      are done. The issue of effective research management is to navigate in this
      reality, ensure inspiration and influx from other environments dealing with
      medical informatics problems, in theory as well as in praxis - and shield the
      individual researcher from emerging bureaucracy, leaving room for creativity.

PMID- 21893892
TI  - Research management in healthcare informatics - experiences from Norway.
AB  - This paper reports on the experiences with establishing a multidisciplinary
      healthcare informatics research community at the Norwegian University of Science
      and Technology (NTNU) in Trondheim, Norway. A multidisciplinary research group in
      healthcare informatics must maintain strong connections to computer science,
      social science, biomedicine and healthcare researchers. Those organizing the
      research must create a milieu that fosters true collaboration across disciplines.
      The researchers must have good access to healthcare institutions, to healthcare
      professionals as well as to patients. A healthcare informatics laboratory creates
      an arena for experiments as well as for validation of health-it technologies.

PMID- 21893893
TI  - Research management: the case of RN4CAST.
AB  - Successful research management requires multifunctional, equal teamwork and
      efficient coordination, aiming to increase the impact of the research outcomes.
      Aim of this paper is to present the strategies that have been followed to
      successfully manage the RN4CAST study, one of the largest multi country research
      projects ever conducted. The paper focuses on the core research strategies rather
      than on the administrative management activities also required for the success of
      this case report. Management of a multi-country nursing survey requires the use
      of common data collection tools, applicable to every context, research protocols
      supporting the scope of the research, data models for multi-country analyses and
      global dissemination strategies.

PMID- 21893894
TI  - eMeasures: a standard format for health quality measures.
AB  - Health quality measures can be used to improve the effective use of Electronic
      Health Record systems (EHRs) in health care delivery. The Health Quality Measures
      Format (HQMF) is a standard for representing a health quality measure as an
      electronic document. This presentation will present the standard, review the
      development process of quality measures for EHR system using HL7 CDA R2, and
      reflect on the outlook for eMeasures implementation and adoption.

PMID- 21893895
TI  - Clinical information systems: cornerstone for an efficient hospital management.
AB  - The university hospitals of Geneva are the largest consortium of public hospitals
      in Switzerland. This organization is born in 1995, after a political decision to
      merge the seven public and teaching hospitals of the Canton of Geneva. From an
      information technologies perspective, it took several years to reach a true
      unified vision of the complete organization. The clinical information system is
      deployed in all sites covering in- and outpatient cares. It is seen as the
      cornerstone of information management and flow in the organization, for direct
      patient care and decision support, but also for the management to drive, improve
      and leverage the activities, for better efficiency, quality and safety of care,
      but also to drive processes. As the system has become more important for the
      organization, it has required progressive changes in its governance. The high
      importance of interoperability and use of formal representation has become a
      major challenge in order to be able to reuse clinical information for real-time
      care and management activities, and for secondary usage such as billing, resource
      management, strategic planning and clinical research. This paper proposes a short
      overview of the tools allowing to leverage the management for physicians, nurses,
      human resources and hospital governance.

PMID- 21893896
TI  - Patient centered integrated clinical resource management.
AB  - The impact of funding systems on the IT systems of providers has been enormous
      and have prevented the implementation of designs to focused on the health issue
      of patients. The paradigm shift the Dutch Ministry of Health has taken in funding
      health care has a remarkable impact on the orientation of IT systems design.
      Since 2007 the next step is taken: the application of the funding concept on
      chronic diseases using clinical standards as the norm. The focus on prevention
      involves the patient as an active partner in the care plan. The impact of the new
      dimension in funding has initiated a process directed to the development of
      systems to support collaborative working and an active involvement of the patient
      and its informal carers. This national approach will be presented to assess its
      international potential, as all countries face the long term care crisis lacking
      resources to meet the health needs of the population.

PMID- 21893897
TI  - ARGOS policy brief on semantic interoperability.
AB  - Semantic interoperability is one of the priority themes of the ARGOS Trans
      Atlantic Observatory. This topic represents a globally recognised challenge that
      must be addressed if electronic health records are to be shared among
      heterogeneous systems, and the information in them exploited to the maximum
      benefit of patients, professionals, health services, research, and industry.
      Progress in this multi-faceted challenge has been piecemeal, and valuable lessons
      have been learned, and approaches discovered, in Europe and in the US that can be
      shared and combined. Experts from both continents have met at three ARGOS
      workshops during 2010 and 2011 to share understanding of these issues and how
      they might be tackled collectively from both sides of the Atlantic. This policy
      brief summarises the problems and the reasons why they are important to tackle,
      and also why they are so difficult. It outlines the major areas of semantic
      innovation that exist and that are available to help address this challenge. It
      proposes a series of next steps that need to be championed on both sides of the
      Atlantic if further progress is to be made in sharing and analysing electronic
      health records meaningfully. Semantic interoperability requires the use of
      standards, not only for EHR data to be transferred and structurally mapped into a
      receiving repository, but also for the clinical content of the EHR to be
      interpreted in conformity with the original meanings intended by its authors.
      Wide-scale engagement with professional bodies, globally, is needed to develop
      these clinical information standards. Accurate and complete clinical
      documentation, faithful to the patient's situation, and interoperability between
      systems, require widespread and dependable access to published and maintained
      collections of coherent and quality-assured semantic resources, including models
      such as archetypes and templates that would (1) provide clinical context, (2) be
      mapped to interoperability standards for EHR data, (3) be linked to well
      specified multi-lingual terminology value sets, and (4) be derived from high
      quality ontologies. There is need to gain greater experience in how semantic
      resources should be defined, validated, and disseminated, how users (who
      increasingly will include patients) should be educated to improve the quality and
      consistency of EHR documentation and to make full use of it. There are urgent
      needs to scale up the authorship, acceptance, and adoption of clinical
      information standards, to leverage and harmonise the islands of standardisation
      optimally, to assure the quality of the artefacts produced, and to organise end
      to-end governance of the development and adoption of solutions.

PMID- 21893898
TI  - Policy needs and options for a common transatlantic approach towards measuring
      adoption, usage and benefits of eHealth.
AB  - The European Union (EU) sponsored ARGOS project analysed current eHealth policy
      thinking in both the EU and the USA, compared strategic challenges and outcomes
      in selected fields, and drafted roadmaps towards developing advanced global
      approaches for these issues. This policy brief focuses on better understanding
      the benefits and costs of eHealth investments, assessing their overall socio
      economic impact, identifying challenges and success factors, as well as measuring
      and globally benchmarking the concrete usage of eHealth solutions. These are by
      now key policy priorities not only of national governments and the European
      Commission, but also of international institutions like WHO or OECD. There is a
      strong felt transatlantic need for stocktaking, identifying lessons learned,
      sharing of experience, and working together to advance these issues for the
      benefit of health systems. A growing number of national and international
      activities can be taken advantage of. Recommendations on how to proceed with such
      transatlantic activities are proposed.

PMID- 21893899
TI  - Policy needs and options for a common approach towards modelling and simulation
      of human physiology and diseases with a focus on the virtual physiological human.
AB  - Life is the result of an intricate systemic interaction between many processes
      occurring at radically different spatial and temporal scales. Every day,
      worldwide biomedical research and clinical practice produce a huge amount of
      information on such processes. However, this information being highly fragmented,
      its integration is largely left to the human actors who find this task
      increasingly and ever more demanding in a context where the information available
      continues to increase exponentially. Investments in the Virtual Physiological
      Human (VPH) research are largely motivated by the need for integration in
      healthcare. As all health information becomes digital, the complexity of health
      care will continue to evolve, translating into an ever increasing pressure which
      will result from a growing demand in parallel to limited budgets. Hence, the best
      way to achieve the dream of personalised, preventive, and participative medicine
      at sustainable costs will be through the integration of all available data,
      information and knowledge.

PMID- 21893900
TI  - Policy brief on the current status of certification of electronic Health Records
      in the US and Europe.
AB  - If Electronic Health Record systems are to provide an effective contribution to
      healthcare, a set of benchmarks need to be set to ensure quality control and
      interoperability of systems. This paper outlines the prevailing status of EHR
      certification in the US and the EU, compares and contrasts established schemes
      and poses opportunities for convergence of activity in the domain designed to
      advance certification endeavours generally. Several EU Member States have in the
      past proceeded with EHR systems quality labeling and/or certification, but these
      differ in scope, in legal framework under which they operate, in policies
      (legislation and financial incentives), in organization, and perhaps most
      importantly in the quality criteria used for benchmarking. Harmonization,
      therefore, became a must. Now, through EuroRec (with approaches ranging from self
      assessment to third party certification depending on the level of confidence
      needed) and its Seals, the possibility to achieve this for EHR systems has
      started in the whole of Europe. The US HITECH Act also attempts to create
      incentives for all hospitals and eligible providers to adopt and use electronic
      information. A centerpiece of the Act is to put in place strong financial
      incentives to adopt and meaningfully use EHRs. The HHS/EHR Certification
      Programme makes use of ISO/IEC 170XX standards for accreditation, testing and
      certification. The approved test method addresses the functional and the
      interoperability requirements defined in the Final Rule criteria and standards.
      To date six Authorized Testing and Certification Bodies (ATCBs) are testing and
      certifying products in the US.

PMID- 21893901
TI  - A proposed vision: the transatlantic observatory for meeting global health policy
      challenges through information and communications technology-enabled solutions
      (ARGOS).
AB  - In 2010 the ARGOS project was funded by the EC (DG RELEX) to contribute to the
      establishement of a "Transatlantic Observatory for meeting Global Health Policy
      Challenges through Information and Communication Technology-enabled solutions" to
      develop and promote common methods for responding to global eHealth challenges in
      the EU and the US. The European Institute for Health Records (EuroRec) was
      coordinating the project. The vision is that the Transatlantic Observatory will
      act as an international platform for dialogue and collaboration on health policy
      issues and will 1. build international consensus about how to improve the access,
      efficiency and quality of health services through ICT, 2. promote the importance
      of interoperability in eHealth, 3. help to define approaches to ensure that
      health data are easily available where it is needed, 4. identify optimal
      development paths.

PMID- 21893902
TI  - Accelerating the deployment of a health information technology and informatics
      workforce through education, training, research, and evaluation.
AB  - Supported by stronger and more coordinated US federal funding and policies,
      driven by goals to deliver care more efficiently, and motivated to provide high
      quality care for an aging and more diverse population, public-private-sector
      organisations are redoubling efforts to implement information systems. Thus,
      there is a critical need to increase and broaden the pool of workers who can help
      organizations maximise the effectiveness of their investments in technology.
      There are in the US various current health informatics education and training
      initiatives and ongoing efforts to accelerate Health IT workforce development.

PMID- 21893903
TI  - eHealth informatics workforce challenges for Europe.
AB  - There is an increasing demand for informatics human resources from major ehealth
      developments aimed at supporting more effective healthcare in many countries.
      Focus to date has been on the standards required to describe ehealth applications
      and solutions; with sporadic attention to the workforce necessary to deliver
      them. There are challenges to ensuring that the ehealth informatics staff
      involved in production and operation of such ehealth systems are 'fit to
      practice' professionals and their competences can be clearly defined. There are
      currently different levels of understanding, quantification and definition of the
      existing and projected workforce requirements across Europe and in the USA. This
      paper highlights some of the issues to be considered across Europe in moving
      towards a situation where the limitations to appropriately skilled staff being
      deployed wherever necessary are reduced and free mobility of the workforce can be
      enabled.

PMID- 21893904
TI  - eHealth information management and informatics workforce challenges for Europe.
AB  - In addition to technology services required to leverage information technology,
      qualified knowledge workers familiar with information management acquisition,
      storage and use and destruction are required to transform the healthcare industry
      to "next generation" status and capabilities. Sound information management
      principles for health information content enables less costly, yet more effective
      results.

PMID- 21893905
TI  - A logical approach to semantic interoperability in healthcare.
AB  - Singapore is in the process of rolling out a number of national e-health
      initiatives, including the National Electronic Health Record (NEHR). A critical
      enabler in the journey towards semantic interoperability is a Logical Information
      Model (LIM) that harmonises the semantics of the information structure with the
      terminology. The Singapore LIM uses a combination of international standards,
      including ISO 13606-1 (a reference model for electronic health record
      communication), ISO 21090 (healthcare datatypes), and SNOMED CT (healthcare
      terminology). The LIM is accompanied by a logical design approach, used to
      generate interoperability artifacts, and incorporates mechanisms for achieving
      unidirectional and bidirectional semantic interoperability.

PMID- 21893906
TI  - Electronic medical record information system for patient consultations in Chinese
      medicine.
AB  - Currently there are no widely used systems to electronically record individual
      patient consultations with Traditional Chinese Medicine (TCM) practitioners. As
      TCM practice differs significantly from western medicine both in diagnosis and
      treatment, using information systems created for western medicine is not
      suitable. There is a need for information systems developed specifically for TCM
      practitioners to manage patient consultation and treatments. Such system should
      be designed to facilitate safe and effective practice by providing decision
      support, utilising existing knowledge such as known herb-drug interactions to
      signal safety risks. Utilising current and developing standards and vocabularies
      such as those developed by the World Health Organisation (WHO) is important to
      facilitate interoperability with other systems. To facilitate continued growth in
      consumer demand, this type of system should be compatible with the needs of the
      individual electronic health records and other medical systems, and provide
      interfaces to external systems such as Medicare, pathology and radiology systems,
      and insurance systems. This paper presents the high level design of a patient
      consultation system for TCM practitioners that addresses the individual
      practitioner's needs for health records entry, storage, retrieval, display and
      support in managing health care delivery to patients and be part of Australia's
      emerging e-health system.

PMID- 21893907
TI  - Vision-based detection of unusual patient activity.
AB  - Automated patient monitoring in hospital environments has gained increased
      attention in the last decade. An important problem is that of behaviour analysis
      of psychiatric patients, where adequate monitoring can minimise the risk of harm
      to hospital staff, property and to the patients themselves. For this task, we
      perform a preliminary investigation on visual-based patient monitoring using
      surveillance cameras. The proposed method uses statistics of optical flow vectors
      extracted from the patient movements to identify dangerous behaviour. In
      addition, the method also performs foreground segmentation followed by blob
      tracking in order to extract shape and temporal characteristics of blobs.
      Dangerous behaviour includes attempting to break out of safe-rooms, self-harm and
      fighting. The features considered include a temporal and multi-resolution
      analysis of blob coarseness, blob area, movement speed and position in the room.
      This information can also be used to normalise the other features according to
      estimated position of the patient in the room. In this preliminary study,
      experiments in a real hospital scenario illustrate the potential applicability of
      the method.

PMID- 21893908
TI  - BioGrid Australia and GRHANITETM: privacy-protecting subject matching.
AB  - BioGrid Australia provide infrastructure for research currently spanning 16
      hospital-based clinical institutions and 50 databases across Victoria, Australia.
      To-date BioGrid have utilised a probabilistic record linkage engine (Sun Oracle
      Java CAPS eIndex) that utilises patient identifiers (albeit in a secure manner)
      during record linkage. BioGrid are now incorporating privacy-protecting record
      linkage technology from the University of Melbourne Rural Health Academic Centre
      (GRHANITETM). For the first time in Australia, the GRHANITETMtechnology is
      allowing primary care data linkage projects to happen on a large scale (70 sites,
      200 planned to date). By utilising GRHANITETMprivacy-protecting record linkage
      technologies, BioGrid are now able to overcome the privacy issues inherent in
      linking data across national jurisdictional boundaries. By utilising
      GRHANITETMprivacy-protecting record linkage technologies all inter-jurisdictional
      public health and hospital clinical data collected by BioGrid can be
      systematically linked to primary care data for research for the first time. This
      paper describes the architecture of the combined BioGrid and GRHANITETMsystems,
      provides evidence of the efficacy of the linkage technologies and heralds the
      start of a new era in privacy-protected, record linked research in Australia.

PMID- 21893909
TI  - Patient journey modelling: using students as a vehicle for the diffusion of
      innovation.
AB  - This paper describes a case study involving third-year undergraduate computing
      students and their conduct of a patient journey modeling project for the
      Ambulatory Care department of a Regional Hospital in New South Wales, Australia.
      The goal of the research was to determine if students, given minimal training in
      an emerging patient journey modeling tool known as Essomenic, could be an
      effective vehicle for the diffusion of innovation to operational staff involved
      in a healthcare improvement project. Under academic supervision, students
      interacted directly with staff to develop models of the current system of care
      from GP referral to the completion of the patient consultation. The methodology
      also included model validation, identification of opportunities for improvement,
      investigation of alternative solutions and solution recommendations. Outcomes of
      the project, conducted over a 14 week semester, demonstrate that the students
      found the technique quick and easy to learn and that they could transfer their
      new found knowledge of this innovation to healthcare staff for the purposes of
      developing true and accurate representations of the current state patient
      journey. Staff were then able to interact directly with the student team, using
      the models as a communication medium, to identify opportunities for improvement
      and understand more deeply, how changes would impact their daily tasks and
      increase patient satisfaction in service delivery.

PMID- 21893910
TI  - Piloting a logic-based framework for understanding organisational change process
      for a health IT implementation.
AB  - This paper describes how a method for evaluating organisational change based on
      the theory of logical types can be used for classifying organisational change
      processes to understand change after the implementation of an electronic
      documentation system in a residential aged care facility. In this instance we
      assess the organisational change reflected by care staff's perceptions of the
      benefits of the new documentation system at one site, at pre-implementation, and
      at 12 months post-implementation. The results show how a coherent view from the
      staff as a whole of the personal benefits, the benefits for others and the
      benefits for the organization create a situation of positive feedback leading to
      embeddedness of the documentation system into the site, and a broader
      appreciation of the potential capabilities of the electronic documentation
      system.

PMID- 21893911
TI  - ICT-based visual interventions addressing social isolation for the aged.
AB  - This paper describes an approach of "visual interventions" to address the effects
      of social isolation imposed by independent living on the aged. This approach
      might be effective in situations where it is not possible to provide enough human
      contact or interaction to stimulate and sustain a positive outlook by the aged
      person. Two ICT-based visual interventions using this approach are described: a
      virtual "picture album" concept which can serve as a basis for positive
      reminiscence, and a virtual "daily assistant" concept to provide advice and
      reminders on health aspects encountered during daily living. A methodological
      approach for validating these concepts is also described.

PMID- 21893912
TI  - A student-centred electronic health record system for clinical education.
AB  - INTRODUCTION: Electronic Health Record (EHR) systems are an increasingly
      important feature of the national healthcare system [1]. However, little research
      has investigated the impact this will have on medical students' learning. As part
      of an innovative technology platform for a new masters level program in medicine,
      we are developing a student-centred EHR system for clinical education. A
      prototype was trialed with medical students over several weeks during 2010. This
      paper reports on the findings of the trial, which had the overall aim of
      assisting our understanding of how trainee doctors might use an EHR system for
      learning and communication in a clinical setting. BACKGROUND: In primary care and
      hospital settings, EHR systems offer potential benefits to medical students'
      learning: Longitudinal tracking of clinical progress towards established learning
      objectives [2]; Capacity to search across a substantial body of records [3];
      Integration with online medical databases [3]; Development of expertise in
      creating, accessing and managing high quality EHRs [4]. While concerns have been
      raised that EHR systems may alter the interaction between teachers and students
      [3], and may negatively influence physician-patient communication [6], there is
      general consensus that the EHR is changing the current practice environment and
      teaching practice needs to respond. METHODS: Final year medical students on
      clinical placement at a large university teaching hospital were recruited for the
      trial. Following a four-week period of use, semi-structured interviews were
      conducted with 10 participants. Audio-recorded interviews were transcribed and
      data analysed for emerging themes. Study participants were also surveyed about
      the importance of EHR systems in general, their familiarity with them, and
      general perceptions of sharing patient records. CONCLUSIONS: Medical students in
      this pilot study identified a number of educational, practical and administrative
      advantages that the student-centred EHR system offered over their existing ad-hoc
      procedures for recording patient encounters. Findings from this preliminary study
      point to the need to introduce and instruct students' on the use of EHR systems
      from their earliest clinical encounters, and to closely integrate learning
      activities based on the EHR system with established learning objectives. Further
      research is required to evaluate the impact of student-centred EHR systems on
      learning outcomes.

PMID- 21893913
TI  - Use of an electronic clinical experience portal for the education of nurses in a
      critical care unit.
AB  - This paper examines a clinical experience portal (CEP) that was developed for
      critical care nurses to access on a personal digital assistant (PDA) while
      undertaking a 12-month postgraduate program. The increasing complexity of care
      provided to patients in intensive care units (ICU) in Australia and overseas
      requires that health care practitioners working in this area are competent and
      highly skilled, to prevent errors and adverse events. The CEP - unlike the
      traditional approach which is often lacking, antiquated or encompassed in paper
      records - provides opportunity for collaborative activities to occur between the
      learner and the teacher in an auditable environment to enhance the quality of the
      education provided. The CEP provided a method for the nurses to record their
      competencies and access educational material within the framework of a
      postgraduate program. The benefits of using the CEP for the education of all
      healthcare professionals' are also discussed.

PMID- 21893914
TI  - Health informatics competencies - underpinning e-health.
AB  - There is a widespread consensus that we have an urgent need to improve our
      workforce capacity in all aspects associated with the skills and knowledge
      required for successful e-health and health informatics developments, associated
      change management and systems implementation strategies. Such activities aim to
      support various health reform policy initiatives. This paper considers the work
      being undertaken by many researchers around the globe to define the range of
      skills and knowledge requirements to suit this purpose. A number of requirements
      and areas of specialisation are detailed. This is followed by descriptions for
      competencies in general and more specifically descriptions of a set of high level
      agreed Health Informatics competencies. Collectively these competencies provide a
      suitable framework useful for the formal recognition of Health Informatics,
      including e-health, as a nationally recognised study discipline. Nationally
      agreed competencies for this discipline enables all education and training
      efforts to be consistently implemented and to fit with the Australian
      Qualifications Framework covering both the Vocational Education and Training
      (VET) and Higher Education sectors.

PMID- 21893915
TI  - Impact of admission and discharge peak times on hospital overcrowding.
AB  - The ability of hospital staff to get a patient to the right bed at the right time
      is dependent on bed occupancy, and is a key issue in all acute hospitals. This
      paper seeks to identify the impact of admission and discharge timing on hospital
      occupancy with reference to the peak in daily admissions and discharges. Patient
      admissions data from 23 Queensland public hospitals was classified into
      categories based on the relative timing of daily admission and discharge curves.
      We found statistically significant differences in mean and peak occupancy and
      patient length of stay between categories (one-way univariate ANOVA p<0.0001).
      The results support early patient discharge initiatives to reduce hospital
      occupancy rates.

PMID- 21893916
TI  - On selecting a clinical trial management system for large scale, multi-centre,
      multi-modal clinical research study.
AB  - Clinical research studies offer many challenges for their supporting information
      systems. AIBL assembled 1112 participants who volunteered crucial information for
      a comprehensive study on neurodegenerative diseases. This paper discusses the
      shortcomings of the clinical trial management system chosen to record the results
      of the study. A set of guidelines was devised and a critique of five systems
      ensued. OpenClinica was selected as the most appropriate option. The main
      contribution of this paper is: (i) proposing a set of guidelines to determine the
      appropriateness of Clinical Trial Management Systems (CTMS) solution; (ii)
      providing a brief critique of existing commercial and open-sourced CTMS; and
      (iii) alluding to some data migration issues and providing cues on how to address
      them. We conclude that open-source CTMS are viable alternatives to the more
      expensive commercial systems to conduct, record and manage clinical studies.

PMID- 21893917
TI  - Synchronised integrated online e-health profiles.
AB  - Web-based social networking applications have become increasingly important in
      recent years. The current applications in the healthcare sphere can support the
      health management, but to date there is no patient-controlled integrator. This
      paper proposes a platform called Multiple Profile Manager (MPM) that enables a
      user to create and manage an integrated profile that can be shared across
      numerous social network sites. Moreover, it is able to facilitate the collection
      of personal healthcare data, which makes a contribution to the development of
      public health informatics. Here we want to illustrate how patients and physicians
      can be benefited from enabling the platform for online social network sites. The
      MPM simplifies the management of patients' profiles and allows health
      professionals to obtain a more complete picture of the patients' background so
      that they can provide better health care. To do so, we demonstrate a prototype of
      the platform and describe its protocol specification, which is an XMPP
      (Extensible Messaging and Presence Protocol) [1] extension, for sharing and
      synchronising profile data (vCard2) between different social networks.

PMID- 21893918
TI  - Mapping the Queensland Health iPharmacy Medication File to the Australian
      Medicines Terminology Using Snapper.
AB  - An exploratory exercise in mapping approximately 8000 medication terms from the
      Queensland Health iPharmacy Medication File to the Australian Medicines
      Terminology (AMT) was carried out to determine coverage, build specialist
      knowledge, and inform future clinical terminology strategies. Snapper was the
      mapping tool selected for this exercise. The Automap function of the tool mapped
      39.2% of the items that were successfully mapped, and the remainder were manually
      mapped. A total of 51.8% of the sample items were mapped to a semantically
      equivalent AMT concept with 50.0% of terms being mapped to a satisfactory fully
      specified term, and 1.8% of terms being mapped to a fully specified term that was
      considered unsuitable for QH clinical purposes. Rules and guidelines on how to
      deal with the emerging differences between the two terminologies were developed
      during the course of the project. Snapper was found to be an appropriate tool for
      this exercise; its functionality is being constantly refined to assist users. As
      a result, this exercise will provide NEHTA with input for the national scope and
      content for AMT, and QH will endeavour to prepare the iPharmacy medication file
      for future interfaces with other terminologies.

PMID- 21893919
TI  - Automatic extraction of cancer characteristics from free-text pathology reports
      for cancer notifications.
AB  - OBJECTIVE: To develop a system for the automatic classification of Cancer
      Registry notifications data from free-text pathology reports. METHOD: The
      underlying technology used for the extraction of cancer notification items is
      based on the symbolic rule-based classification methodology, whereby formal
      semantics are used to reason with the systematised nomenclature of medicine -
      clinical terms (SNOMED CT) concepts identified in the free text. Business rules
      for cancer notifications used by Cancer Registry coding staff were also
      incorporated with the aim to mimic Cancer Registry processes. RESULTS: The system
      was developed on a corpus of 239 histology and cytology reports (with 60%
      notifiable reports), and then evaluated on an independent set of 300 reports
      (with 20% notifiable reports). Results show that the system can reliably classify
      notifiable reports with 96% and 100% specificity, and achieve an overall accuracy
      of 82% and 74% for classifying notification items from notifiable reports at a
      unit record level from the development and evaluation set, respectively.
      CONCLUSION: Cancer Registries collect a multitude of data that requires manual
      review, slowing down the flow of information. Extracting and providing an
      automatically coded cancer pathology notification for review can lessen the
      reliance on expert clinical staff, improving the efficiency and availability of
      cancer information.

PMID- 21893920
TI  - Interactive visualisation with user perspective for biological data analysis.
AB  - With an astonishing amount of genomic data generated for processing in medical
      field, it is essential to provide an effective methodology for understanding,
      reasoning and supporting decision making of large information spaces. This paper
      presents an interactive interface that provides a mechanism to analyse large
      scale biological and clinical data. This aims to provide a much greater
      flexibility and control for the domain experts to interactively customise the
      visualisation according to their preferences.

PMID- 21893921
TI  - Healthy connections: online social networks and their potential for peer support.
AB  - Social and professional support for mental health is lacking in many rural areas 
      highlighting the need for innovative ways to improve access to services. This
      study explores the potential of online social networking as an avenue for peer
      support. Using a cross sectional survey, 74 secondary students answered questions
      relating to internet use, online social network use and perceptions of mental
      health support. Over half of the sample had experienced a need for mental health
      support with 53% of participants turning to the internet. Results indicate that
      online social networking sites were used regularly by 82% of the sample and 47%
      believed these sites could help with mental health problems. The study concluded
      that online social networking sites may be able to link young people together
      with others in similar situations. The popularity and frequency of use may allow
      these sites to provide information, advice and direction for those seeking help.

PMID- 21893922
TI  - Building an advanced wireless end-to-end emergency medical system.
AB  - Effective communication in healthcare is important and especially critical in
      emergency situations. In this paper we propose a new comprehensive emergency
      system which will facilitate the communication process in emergency cases from
      ambulance dispatch to the patient's arrival and handover in the hospital. The
      proposed system has been designed to facilitate and computerise all the processes
      involved in an accident from finding the nearest ambulance through to accessing a
      patient's online health record which can assist in pre-hospital treatments. The
      proposed system will also locate the nearest hospital specialising in the
      patient's condition and will communicate patient identification to the emergency
      department. The components of the proposed system and the technologies used in
      building this system are outlined in this paper as well as the challenges
      expected and proposed solutions to these challenges.

PMID- 21893923
TI  - Machine intelligence for health information: capturing concepts and trends in
      social media via query expansion.
AB  - INTRODUCTION: We aim to improve retrieval of health information from Twitter.
      BACKGROUND: The popularity of social media and micro-blogs has emphasised their
      potential for knowledge discovery and trend building. However, capturing and
      relating concepts in these short-spoken and lexically extensive sources of
      information requires search engines with increasing intelligence. METHODS: Our
      approach uses query expansion techniques to associate query terms with the most
      similar Twitter terms to capture trends in the gamut of information. RESULTS: We
      demonstrated the value, defined as improved precision, of our search engine by
      considering three search tasks and two independent annotators. We also showed the
      stability of the engine with an increasing number of tweets; this is crucial as
      large data sets are needed for capturing trends with high confidence. These
      results encourage us to continue developing the engine for discovering trends in
      health information available at Twitter.

PMID- 21893924
TI  - How accurate is the electronic health record? - a pilot study evaluating
      information accuracy in a primary care setting.
AB  - BACKGROUND: Electronic health records (EHR) are increasingly used for both
      administrative and clinical tasks with major implications for patient safety and
      quality of care. This study aims to determine a baseline EHR level of accuracy
      present on measurable information fields within an Australian general practice.
      METHODS: Quantitative and descriptive pilot study of patients attending a private
      general practice. Patients who consented to participate in the study had their
      patient records reviewed to determine how many items were correct, incorrect or
      not recorded in each EHR information field. Statistical analysis was performed on
      the data collected. RESULTS: A total of 33 patients gave consent to participate
      in this study. High levels of accuracy were found in the area of demographic
      details (94%). Moderately high levels of accuracy were reported for allergies
      (61%) but also a considerable percentage of non-recorded information was present
      (36%). Inaccuracies in medication lists were reported in 51% of records reviewed
      with 32.1% of all medications being inaccurately recorded. While over 91% of
      participants had a history summary with eight or less items present, omissions
      were reported for one in every five participants. There were no significant
      associations present between inaccurate data and frequency of practice visits or
      those with more than five past medical conditions listed in the EHR. CONCLUSION:
      The study has confirmed that errors and inaccuracies exist in EHR in our
      Australian pilot study. The pilot study has also allowed us to complete a trial
      ensuring that a study of this type can be done safely and with correct
      methodology. As health informatics plays an increasingly important role in health
      care, studies of this type will better inform practitioners/ researchers in
      designing systems to ensure quality electronic patient information.

PMID- 21893925
TI  - A pilot study on understanding the journey of advanced prostate cancer patients.
AB  - OBJECTIVE: To understand the journey of advanced prostate cancer patients for
      supporting development of an innovative patient journey browser. BACKGROUND:
      Prostate cancer is one of the common cancers in Australia. Due to the chronic
      nature of the disease, it is important to have effective disease management
      strategy and care model. Multi-disciplinary care is a well-proven approach for
      chronic disease management. The Multi-disciplinary team (MDT) can function more
      effectively if all the required information is available for the clinical
      decision support. The development of innovative technology relies on an accurate
      understanding of the advanced prostate cancer patient's journey over a prolonged
      period. This need arises from the fact that advanced prostate cancer patients may
      follow various treatment paths and change their care providers. As a result of
      this, it is difficult to understand the actual sources of patient's clinical
      records and their treatment patterns. The aim of the research is to understand
      variable sources of clinical records, treatment patterns, alternative therapies,
      over the counter (OTC) medications of advanced prostate cancer patients. This
      study provides better and holistic understanding of advanced prostate cancer
      journey. METHODS: The study was conducted through an on-line survey developed to
      seek and analyse the responses from the participants. The on-line questionnaire
      was carefully developed through consultations with the clinical researchers at
      the Australian Prostate Cancer Research Centre-Queensland, prostate cancer
      support group representatives and health informaticians at the Australian E
      Health Research Centre. The non-identifying questionnaire was distributed to the
      patients through prostate cancer support groups in Queensland, Australia. The
      pilot study was carried out between August 2010 and December 2010. RESULTS: The
      research made important observations about the advanced prostate cancer journey.
      It showed that General Practitioner (GP) was the common source of patient's
      clinical records (41%) followed by Urologist (14%) and other clinicians (14%).
      The data analysis also showed that selenium was the common complementary
      supplement (55%) used by the patients and about 48% patients did not use any OTC
      drugs. The most common OTC used by the patients was Paracetamol (about 45%).
      CONCLUSION: The results have provided a foundation to the architecture of the
      proposed technology solution. The outcomes of this study are incorporated in
      design of the proposed patient journey browser system. A basic version of the
      system is currently being used at the advanced prostate cancer MDT meetings.

PMID- 21893926
TI  - Observing effectiveness of pathology ordering controls in emergency departments.
AB  - OBJECTIVE: To demonstrate application of data integration technology for
      observing the effectiveness of interventions to control pathology orders in
      Emergency Departments. BACKGROUND: Doctors frequently need to order blood tests
      in the Emergency Departments as a part of diagnostic set up in Emergency
      Departments. However, pathology test ordering is excessive and often unnecessary.
      The excessive ordering of blood test places a significant financial burden on our
      health care system. It also causes undue discomfort and worry to the patients.
      There are many interventions employed to control pathology ordering in Emergency
      Departments. The analysis of effectiveness of interventions is required for
      improving clinical practices in Emergency Departments. However, the collection
      and extraction of data on the effects of intervention can be very costly and time
      consuming. Therefore, there is a need of a technology-based solution to access,
      query and analyse data residing across different sources. METHODS: The research
      aims to determine efficacy of an intervention called the "Traffic Light System"
      through a pathology request form used to control the pathology ordering in one
      adult hospital emergency department. Health Data Integration (HDI) technology was
      implemented to link and query the data residing at different source systems i.e.
      pathology and ED information system. The data was extracted from the Emergency
      Department Information System at an adult tertiary hospital in Queensland. Twenty
      weeks of pre-intervention data was collected. Twenty weeks of post-intervention
      data was collected after 32-week transition interval. The data for pre
      intervention, transition and post-intervention period was analysed to assess the
      effectiveness of the intervention in reducing commonly ordered pathology tests
      such as Full Blood Counts (FBC) and Erythrocyte Sedimentation Rate (ESR).
      RESULTS: The total number of FBC tests ordered in the pre-intervention period
      fell slightly in the post-intervention period (mean 42.3 vs 38.1 per 100
      patients). The total number Erythrocyte Sedimentation Rate tests showed a
      significant declining trend as a result of ED intervention (2.5 vs 1.4 per 100
      patients, p=0.001). HDI completed the task of data extraction, manipulation and
      querying in seconds. A manual check of a sample of 200 pathology test orders
      shows 95.5% sensitivity, which is considered accurate enough for this purpose.
      CONCLUSION: Pathology ordering can be reduced using sustainable protocols. This
      work has demonstrated HDI capability to extract and link pathology data
      efficiently to evaluate an ED intervention.

PMID- 21893927
TI  - Is the biggest security threat to medical information simply a lack of
      understanding?
AB  - Connecting Australian health services and the e-health initiative is a major
      focus in the current health environment. Many issues are presented as key to its
      success including solving issues with confidentiality and privacy. However, the
      main problem may not be these issues in sharing information but the fact that the
      point of origin of such records is still relatively insecure. This paper
      highlights why this may be the case. Research into the security of medical
      information has shown that many primary healthcare providers are unable to create
      an environment with effective information security. Numerous factors contribute
      to this complex situation including a trustful environment, the resultant
      security culture and the capability of individual healthcare organisations.
      Further, the growing importance of new directions in the use of patient
      information is considered. This paper discusses these issues and positions them
      within the complex environment that is healthcare. In our current health system
      infrastructure, the points of origin of patient information are our most
      vulnerable. This entwined with progressively new uses of this information expose
      additional security concerns, such as re-identification of information, that
      require attention.

PMID- 21893928
TI  - Development of an automated physical activity classification application for
      mobile phones.
AB  - BACKGROUND: Physical activity classification is an objective approach to assess
      levels of physical activity, and indicates an individual's degree of functional
      ability. It is significant for a number of the disciplines, such as behavioural
      sciences, physiotherapy, etc. Accelerometry is found to be a practical and low
      cost method for activity classification that could provide an objective and
      efficient measurement of people's daily activities. METHODS: This paper utilises
      a mobile phone with a built-in tri-axial accelerometer sensor to automatically
      classify normal physical activities. A rule-based activity classification model,
      which can recognise 4 common daily activities (lying, walking, sitting, and
      standing) and 6 transitions between postural orientations, is introduced here. In
      this model, three types of statuses (walking/ transition, lying, and
      sitting/standing) are first classified based on the kinetic energy and upright
      angle. Transitions are then separated from walking and assigned to the
      corresponding type using upright angle algorithm. To evaluate the performance of
      this developed application, a trial is designed with 8 healthy adult subjects,
      who are required to perform a 6-minute activity routine with an iPhone fixed at
      the waist position. RESULTS: Based on the evaluation result, our application
      measures the length of time of each activity accurately and the achieved
      sensitivity of each activity classification exceeds 90% while the achieved
      specificity exceeds 96%. Meanwhile, regarding the transition identification, the
      sensitivities are high in stand-to-sit (80%) and low in sit-to-stand (56%).

PMID- 21893929
TI  - Metastatic mucinous adenocarcinoma of the ovary is characterized by advanced
      patient age, small tumor size, and elevated serum CA125.
AB  - BACKGROUND/AIMS: An intraoperative diagnosis in cases with primary and metastatic
      ovarian carcinomas is important for adequate treatment. The aim of the present
      study was to find a reliable method to discriminate primary from metastatic
      mucinous adenocarcinomas (MACs) of the ovary intraoperatively. METHODS: Clinical
      features of all primary and metastatic mucinous ovarian carcinomas diagnosed from
      1994 to 2008 at the Osaka University and Osaka Rosai Hospitals, Osaka, Japan,
      were reviewed retrospectively. RESULTS: Among the 73 MACs, 51 (70%) and 22 cases
      (30%) were diagnosed as primary and metastatic ovarian carcinomas, respectively.
      The distributions of tumor size, patient age, and serum CA125 level were
      significantly different between primary and metastatic cases. Our algorithm that
      categorizes patients >=50 years whose tumor size was <10 cm into metastatic
      cases, and patients <50 years, or the ones whose tumor size was >=10 cm, into
      primary tumors, provided an 84% accuracy in our population. CONCLUSIONS: A more
      reliable method to discriminate primary from metastatic MACs of the ovary by
      patient age and serum tumor markers was derived from our study population.

PMID- 21893930
TI  - Age-dependent physiological changes in the histoarchitecture of the articular
      cartilage of the rabbit mandibular condyle: a morphological and morphometric
      study.
AB  - Mandibular condyle articular cartilage participates in condylar postnatal growth
      and is responsible for adaptations to anatomical and/or biomechanical alterations
      throughout life. In a preliminary study in rabbits, differences were observed in
      the thickness of the layers of articular cartilage in control animals at 5 and 6
      months (generally considered adults for this purpose). This study aimed to
      describe sagittally sectioned condylar cartilages stained with Picrosirius
      hematoxylin in rabbits at 40 days and 5, 6, 8, 13, and 18 months to determine
      when histological maturity is reached. At 40 days, 5 layers were seen: fibrous,
      proliferative, transition, maturation, and hypertrophic. Older animals (5-18
      months) lacked the transition layer. Fibrous, proliferative, and hypertrophic
      regions were considered for morphometric analysis. The thickness of the fibrous
      region did not change during the analyzed period (p = 0.1899). When proliferative
      and hypertrophic regions and the total thickness of the cartilage were compared,
      a difference was detected (p < 0.001). The thickness of the proliferative region
      was greatest at 40 days and decreased at 5 months; however, it increased at 6
      months, when it was significantly thicker than at 5, 8, 13, and 18 months. Both
      the hypertrophic region and the total thickness were thickest at 40 days,
      intermediate at 5, 6, and 8 months, and thinnest at 13 and 18 months. In summary,
      our data suggest a physiological period of increased cartilage growth at 6
      months. Additionally, rabbits at this age should be avoided in experiments
      involving condylar cartilage. Finally, 13-month-old rabbits have reached
      histological maturity of the condylar cartilage.

PMID- 21893931
TI  - Priming of mesenchymal stem cells with oxytocin enhances the cardiac repair in
      ischemia/reperfusion injury.
AB  - Oxytocin stimulates the cardiomyogenesis of embryonic stem cells and adult
      cardiac stem cells. We previously reported that oxytocin has a promigratory
      effect on umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs). In this
      study, UCB-MSCs were cultured with oxytocin and examined for their therapeutic
      effect in an infarcted heart. UCB-MSCs were pretreated with 100 nM oxytocin and
      cardiac markers were assessed by immunofluorescence staining. Next, oxytocin
      supplemented USC-MSCs (OT-USCs) were cocultured with hypoxia/reoxygenated
      neonatal rat cardiomyocytes and cardiac markers and dye transfer were then
      examined. For the in vivo study, ischemia/reperfusion was induced in rats, and
      phosphate-buffered saline (group 1), 1-day OT-USCs (group 2), or 7-day OT-USCs
      (group 3) were injected into the infarcted myocardium. Two weeks after injection,
      histological changes and cardiac function were examined. UCB-MSCs expressed
      connexin 43 (Cnx43), cardiac troponin I (cTnI), and alpha-sarcomeric actin (alpha
      SA) after oxytocin supplementation and coculture with cardiomyocytes. Functional
      gap junction formation was greater in group 3 than in groups 1 and 2. Cardiac
      fibrosis and macrophage infiltration were lower in group 3 than in group 2.
      Restoration of Cnx43 expression was greater in group 3 than in group 2. Cnx43-
      and cTnI-positive OT-USCs in the peri-infarct zone were observed in group 2 and
      more frequently in group 3. The ejection fraction (EF) was increased in groups 2
      and 3 in 2 weeks. The improved EF was sustained for 4 weeks only in group 3. Our
      findings suggest that the supplementation of UCB-MSCs with oxytocin can
      contribute to the cardiogenic potential for cardiac repair.

PMID- 21893932
TI  - Detection of four germ cell markers in rats during testis morphogenesis:
      differences and similarities with mice.
AB  - Germ cells are the only cells capable of transmitting genetic information from
      generation to generation. Germ cell development has been widely studied in
      different species. Among mammals, the mouse is the model used in the majority of
      studies on germ cell differentiation, sex determination and genetics. In the
      present study, we suggest that the rat is also a very important model for the
      investigation of the mechanisms of germ cell development. To study rat germ cell
      development and compare it with that of mouse, the germ cell markers germ cell
      nuclear antigen 1 (GCNA1), OCT4, mouse vasa homologue (MVH) and specific surface
      embryonic antigen 1 (SSEA1) were immunolabeled at different phases of embryonic
      and postnatal development. SSEA1 and GCNA1 were not detected in rat primordial
      germ cells and fetal gonocytes. GCNA1 was detected postnatally and was present
      only in leptotene, zygotene and early pachytene spermatocytes. On the other hand,
      in mice, these markers were detected in germ cells as soon as 11.5 days
      postcoitum (dpc). MVH was detected in migrating rat primordial germ cells as well
      as in those that have already colonized the gonads, whereas in mice, MVH is
      detected only in germ cells that have reached the gonads. In rats, OCT4-positive
      germ cells were detected from 13 to 17 dpc, but not at 19 dpc or in postnatal
      testes. This is in contrast with mice that show OCT4 labeling in both embryonic
      and adult testes. These data suggest that primordial germ cell development in
      rats and mice shows considerable differences and that the rat may also be an
      important model to study the embryonic development of germ cells.

PMID- 21893933
TI  - The effect of serial passaging on the proliferation and differentiation of bovine
      adipose-derived stem cells.
AB  - Adipose-derived stem cells (ASCs) represent an excellent cell source for the
      development of regenerative therapies for a broad variety of tissue disorders.
      Commonly, in vitro expansion is necessary to obtain sufficient cell populations
      for research purposes and clinical applications. Although it has been
      demonstrated that human ASCs can maintain their adipogenic, chondrogenic and
      osteogenic potential in long-term culture (up to 15 passages), it is not
      guaranteed that a satisfactory level of differentiation is achievable in later
      passages. In this study, we investigated the self-renewal and multilineage
      differentiation capacity of bovine ASCs, isolated from the interdigital fat pad,
      and explored how serial passaging influences the cells. A proliferation study
      examined the changes in growth kinetics from passage 1 to 5, and multilineage
      (adipogenesis, chondrogenesis and osteogenesis) differentiation studies were
      conducted to compare the potential between passage 2 (P2) and passage 5 (P5).
      From the proliferation study, a statistically significant change in the doubling
      time did not appear until P5. In the differentiation study, both P2 and P5 ASCs
      could be stimulated to undergo multilineage differentiation under specific
      culturing conditions. However, adipogenic and chondrogenic cultures showed
      significantly lower levels of differentiation in the P5-induced cultures. In
      contrast, P5-induced osteogenic cultures had higher alkaline phosphatase enzyme
      activity than P2-induced cultures, suggesting an increase in the osteogenic
      response with serial passaging. Overall, bovine ASCs are capable of self-renewal
      and multilineage differentiation; however, long-term in vitro expansion has a
      negative effect on adipogenic and chondrogenic differentiation, while potentially
      favoring osteogenesis.

PMID- 21893934
TI  - Stable precursor fragments of vasoactive peptides in umbilical cord blood of term
      and preterm infants.
AB  - BACKGROUND: Though various neurohormonal systems are concurrently activated
      during birth, their biological effectors are not always easy to measure due to
      their short half-life in vivo, instability in biological samples, or very low
      concentrations. METHODS: Using a recently discovered chemiluminescence assay, we
      measured the stable precursor fragments mid-regional pro-atrial natriuretic
      peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro
      endothelin-1 (CT-proET-1) and C-terminal pro-vasopressin (CT-proAVP or copeptin)
      immediately after birth in umbilical venous cord blood from 119 infants with a
      gestational age of 23-42 weeks and evaluated their possible functions. RESULTS:
      Cord blood levels of MR-proANP, MR- proADM, CT-proET-1, and CT-proAVP were
      considerably higher compared with normal adult levels. The CT-proAVP
      concentrations were 10-fold higher in term, and 70-fold higher in extremely
      preterm infants. MR-proANP showed 4-fold higher levels in term infants and 20
      fold higher levels in extremely preterm infants. Levels of MR-proADM and CT-proET
      1 were 2- to 3-fold higher in preterm and term infants. All four parameters
      showed significantly decreased values with increasing gestational age and a
      significant correlation between CT-proET-1 and MR-proADM. CONCLUSION: Our results
      indicate that vasoactive and natriuretic mediators play a functionally relevant
      role in circulatory transition from fetal to neonatal life.

PMID- 21893935
TI  - Perinatal selective serotonin reuptake inhibitor exposure: impact on brain
      development and neural plasticity.
AB  - Selective serotonin reuptake inhibitor (SSRI) medications are the most common
      antidepressant treatment used during pregnancy and the postpartum period. Up to
      10% of pregnant women are prescribed SSRIs. Serotonin plays an integral part in
      neurodevelopment, and questions have been raised about the placental transfer of
      SSRIs and the effects of preventing reuptake of presynaptic serotonin on fetal
      neurodevelopment. Preclinical data is beginning to document a role of early
      exposure to SSRIs in long-term developmental outcomes related to a number of
      brain regions, such as the hippocampus, cortex and cerebellum. To date, the
      majority of preclinical work has investigated the developmental effects of SSRIs
      in the offspring of healthy mothers; however, more research is needed on the
      effects of these medications in the face of maternal adversity. This minireview
      will highlight emerging evidence from clinical and preclinical studies
      investigating the impact of perinatal SSRI exposure on brain development and
      neural plasticity.

PMID- 21893936
TI  - Chemo- and thermosensory responsiveness of Grueneberg ganglion neurons relies on
      cyclic guanosine monophosphate signaling elements.
AB  - Neurons of the Grueneberg ganglion (GG) in the anterior nasal region of mouse
      pups respond to cool temperatures and to a small set of odorants. While the
      thermosensory reactivity appears to be mediated by elements of a cyclic guanosine
      monophosphate (cGMP) cascade, the molecular mechanisms underlying the odor
      induced responses are unclear. Since odor-responsive GG cells are endowed with
      elements of a cGMP pathway, specifically the transmembrane guanylyl cyclase
      subtype GC-G and the cyclic nucleotide-gated ion channel CNGA3, the possibility
      was explored whether these cGMP signaling elements may also be involved in
      chemosensory GG responses. Experiments with transgenic mice deficient for GC-G or
      CNGA3 revealed that GG responsiveness to given odorants was significantly
      diminished in these knockout animals. These findings suggest that a cGMP cascade
      may be important for both olfactory and thermosensory signaling in the GG.
      However, in contrast to the thermosensory reactivity, which did not decline over
      time, the chemosensory response underwent adaptation upon extended stimulation,
      suggesting that the two transduction processes only partially overlap.

PMID- 21893937
TI  - From targets to treatments: a review of molecular targets in pancreatic
      neuroendocrine tumors.
AB  - Pancreatic neuroendocrine tumors (pancreatic NET) are relatively rare, slowly
      growing tumors, although their incidence is increasing, and patients may survive
      for several years with metastatic disease. Apart from symptomatic relief, there
      have been few treatment options for these tumors in the past. More recently,
      investigators have explored the potential of molecularly targeted agents in
      treating pancreatic NET, with some success. In this review, we consider the data
      supporting exploitation of different targets in pancreatic NET, including peptide
      receptors, receptor tyrosine kinases (involved in tumor angiogenesis and more
      directly supporting tumor growth), and intracellular targets, such as the
      mammalian target of rapamycin (mTOR), which has a central role in regulating cell
      growth, metabolism, and apoptosis. Probably due to the paucity of pancreatic NET,
      many clinical trials to date have included heterogeneous NET populations, and
      there are few randomized studies of this specific patient population. Very
      recently, promising results have been achieved in placebo-controlled, phase III
      trials with the multitargeted tyrosine kinase inhibitor, sunitinib, and the mTOR
      inhibitor, everolimus. These agents have been approved or are currently being
      reviewed by authorities for use in patients with pancreatic NET. Here we review
      potential molecular targets in pancreatic NET and summarize the available data
      for targeted agents from phase II and III trials open to patients with this
      tumor.

PMID- 21893938
TI  - The psychiatric presentation of fragile x: evolution of the diagnosis and
      treatment of the psychiatric comorbidities of fragile X syndrome.
AB  - Fragile X syndrome (FXS) is the leading inherited cause of mental retardation and
      autism spectrum disorders worldwide. It presents with a distinct behavioral
      phenotype which overlaps significantly with that of autism. Unlike autism and
      most common psychiatric disorders, the neurobiology of fragile X is relatively
      well understood. Lack of the fragile X mental retardation protein causes
      dysregulation of synaptically driven protein synthesis, which in turn causes
      global disruption of synaptic plasticity. Thus, FXS can be considered a disorder
      of synaptic plasticity, and a developmental disorder in the purest sense:
      mutation of the FMR1 (fragile X mental retardation 1) gene results in abnormal
      synaptic development in response to experience. Accumulation of this abnormal
      synaptic development, over time, leads to a characteristic and surprisingly
      consistent behavioral phenotype of attention deficit, hyperactivity, impulsivity,
      multiple anxiety symptoms, repetitive/perseverative/stereotypic behaviors,
      unstable affect, aggression, and self-injurious behavior. Many features of the
      behavioral and psychiatric phenotype of FXS follow a developmental course, waxing
      and waning over the life span. In most cases, symptoms present as a mixed
      clinical picture, not fitting established diagnostic categories. There have been
      many clinical trials in fragile X subjects, but no placebo-controlled trials of
      adequate size or methodology utilizing the most commonly prescribed psychiatric
      medications. However, large and well-designed trials of investigational agents
      which target the underlying pathology of FXS have recently been completed or are
      under way. While the literature offers little guidance to the clinician treating
      patients with FXS today, potentially disease-modifying treatments may be
      available in the near future.

PMID- 21893940
TI  - Progressive osteolytic calvarial lesions in children after minor head injury.
AB  - OBJECTIVE: Osteolytic lesions of the skull in children have a broad differential
      diagnosis including congenital, inflammatory and neoplastic lesions. Progressive
      osteolysis of the skull secondary to head trauma is rare and has been poorly
      characterized. METHODS: The pediatric database at our hospital was screened for
      children with osteolytic lesions who had a previous mild head injury without
      fracture or dural tears. We identified 2 children with circumscribed progressive
      cranial osteolysis after minor head trauma detected by CT and MRI scans. Three
      additional cases were found in a review of the published literature. RESULTS: Ten
      children with an osteolytic skull lesion treated between January 1998 and
      February 2008 were identified in our pediatric database. In 2 children there was
      evidence of previous mild head injury without a skull fracture. Trauma had
      occurred 7 and 2 months prior to presentation, respectively. The inner table of
      the skull was intact in both cases. In 1 case, surgery was performed, and in the
      other case, a wait-and-see strategy was adopted. Pathological examination in case
      1 revealed an organized hemorrhage with focal papillary endothelial hyperplasia.
      CONCLUSIONS: Progressive osteolytic calvarial lesions may occur in both infants
      and adolescents after mild head injury. They involve either only the diploe and
      outer table of the skull or both the inner and outer tables. These lesions might
      be due to intradiploic or subgaleal hematomas triggering an inflammatory process.
      While surgical resection can be considered to confirm a histopathological
      diagnosis and to exclude other diagnoses, spontaneous reossification is possible.

PMID- 21893941
TI  - Metabolic impact of growth hormone treatment in short children born small for
      gestational age.
AB  - BACKGROUND: Growth hormone (GH) treatment in short children born small for
      gestational age (SGA) may result in metabolic changes with potential long-term
      effects. METHODS: 149 short SGA children (mean birth weight 2.0 +/- 0.6 kg, age
      5.5 +/- 1.5 years, height standard deviation score (SDS) -3.1 +/- 0.6) were
      randomised to: low-dose GH therapy (0.033 mg/kg/day) for 2 years; high-dose GH
      therapy (0.100 mg/kg/day) for 1 year, or mid-dose GH therapy (0.067 mg/kg/day)
      for 1 year. Leptin, ghrelin, insulin-like growth factor-I (IGF-I), IGF binding
      protein-1 (IGFBP-1), lipids, fasting blood glucose and fasting insulin were
      assessed at baseline, 12 and 24 months. RESULTS: After 1 year of active
      treatment, GH significantly reduced serum ghrelin and increased IGF-I SDS and
      insulin levels. Regression analysis showed an inverse correlation between ghrelin
      and IGF-I SDS (p < 0.001). Leptin and IGFBP-1 also declined (both p < 0.05).
      Changes in insulin levels reversed upon discontinuation. Improvements in lipid
      profile were nonsignificant and fasting blood glucose levels remained within the
      normal range. CONCLUSION: In short SGA children, ghrelin and leptin reductions
      associated with GH treatment may occur through a negative feedback loop of the GH
      IGF-I axis. Consequently, via ghrelin and leptin suppression, GH treatment may
      modify food intake and body composition and potentially improve long-term
      metabolic outcomes.

PMID- 21893939
TI  - Amygdala regulation of fear and emotionality in fragile X syndrome.
AB  - Fear is a universal response to a threat to one's body or social status.
      Disruption in the detection and response of the brain's fear system is commonly
      observed in a variety of neurodevelopmental disorders, including fragile X
      syndrome (FXS), a brain disorder characterized by variable cognitive impairment
      and behavioral disturbances such as social avoidance and anxiety. The amygdala is
      highly involved in mediating fear processing, and increasing evidence supports
      the idea that inhibitory circuits play a key role in regulating the flow of
      information associated with fear conditioning in the amygdala. Here, we review
      the known and potential importance of amygdala fear circuits in FXS, and how
      developmental studies are critical to understand the formation and function of
      neuronal circuits that modulate amygdala-based behaviors.

PMID- 21893942
TI  - Primary mucinous adenocarcinoma of the renal pelvis with elevated CEA and CA19-9.
AB  - Primary adenocarcinoma of the renal pelvis is rarely reported in the literature.
      Here we present a case of primary mucinous adenocarcinoma of the renal pelvis
      with elevated serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9
      (CA19-9) levels. A 56-year-old woman was referred to our center with intermittent
      fever and left-sided back pain for 1 month. Computed tomography showed bilateral
      nephrolithiasis, mild right hydronephrosis and left pyonephrosis accompanied with
      ambiguous soft tissues. A radionucleorenogram showed that the glomerular
      filtration rate of the left and right kidney was 0 and 79 ml/min, respectively.
      Left nephrectomy was performed without lymph node dissection. Histopathology
      revealed mucinous adenocarcinoma and elevated serum CEA and CA19-9 levels were
      found. She died of multiorgan metastasis after 5 months. A review of the
      literature is also reported.

PMID- 21893943
TI  - Pilot study of the association between the HLA region and testicular carcinoma
      among Croatian patients.
AB  - OBJECTIVES: To analyze the distribution of HLA alleles and HLA microsatellite
      alleles in Croatian patients with testicular carcinoma, compare it with that of
      healthy controls and investigate whether the polymorphism within the HLA region
      could be associated with the development of testicular cancer. METHODS: Genomic
      DNA was isolated from the peripheral blood of 24 patients with testicular germ
      cell tumors (TGCT). Patients and controls were typed for HLA class I and class II
      polymorphism by the PCR-SSO method. Nine HLA microsatellites were analyzed by PCR
      and electrophoresis in an automated sequencer. RESULTS: No significant deviation
      in the distribution of frequencies at HLA class I alleles was observed between
      patients and controls. Among HLA class II alleles, a statistically significant
      increase in the frequency of the HLA-DPB1*1701 allele was found among patients.
      The frequency of the HLA-DRB1*07-DQA1*0201-DQB1*0202 haplotype was increased in
      patients in comparison to the controls. Analysis of HLA microsatellites showed an
      increased frequency of D6S291-3 allele (p(corr) = 0.0455, OR = 3.05) among
      patients. CONCLUSIONS: The observed association of the disease and the DPB1*1701
      allele as well as with the D6S291-3 allele suggests that this part of the HLA
      region might be involved in the pathogenesis of TGCT. Our data provide a basis
      for further studies about the correlation between the HLA region and testicular
      cancer.

PMID- 21893944
TI  - Drosophila as a developmental paradigm of regressive brain evolution: proof of
      principle in the visual system.
AB  - Evolutionary developmental biology focuses heavily on the constructive evolution
      of body plan components, but there are many instances such as parasitism, cave
      adaptation, or postembryonic growth rate optimization where evolutionary
      regression is of adaptive value. This is particularly true in the nervous system
      because of its massive energy costs. However, comparatively little effort has
      thus far been made to understand the evolutionary developmental trajectories of
      adaptive nervous system reduction. This review focuses on the organization and
      evolution of the Drosophila larval brain, which represents an exceptional example
      of miniaturization, most dramatically in the visual system. It is specifically
      discussed how the dependency of outer optic lobe development on retinal
      innervation can be assumed to have facilitated a first evolutionary phase of
      larval visual system reduction. Afferent input-contingent development of neu- ral
      compartments very likely plays a widespread role in adaptive brain evolution.
      Understanding the complete deconstruction of the larval optic neuropiles in
      Drosophila awaits expanded comparative analysis but has the promise to inform
      about further developmental trajectories and mechanisms underlying regressive
      evolution of the brain.

PMID- 21893945
TI  - Participatory and persuasive telehealth.
AB  - Technological advances in telehealth systems are primarily focused on sensing and
      monitoring. However, these systems are limited in that they only rely on sensors
      and medical devices to obtain vital signs. New research and development are
      urgently needed to offer more effective and meaningful interactions between
      patients, medical professionals and other individuals around the patients. Social
      networking with Web 2.0 technologies and methods can meet these demands, and help
      to develop a more complete view of the patient. Also many people, including the
      elderly, may be resistant to change, which can reduce the efficacy of telehealth
      systems. Persuasive technology and mechanisms are urgently needed to counter this
      resistance and promote healthy lifestyles. In this paper, we propose the
      participatory and persuasive telehealth system as a solution for these two
      limitations. By integrating connected health solutions with social networking and
      adding persuasive influence, we increase the chances for effective interventions
      and behavior alterations.

PMID- 21893946
TI  - Comments on dietary restriction, Okinawa diet and longevity.
AB  - Longevity in Okinawa is considered to be a result of traditional low calorie
      diet. Le Bourg suggests that Okinawa is an example of severe malnutrition, which
      is harmful for later generations. We believe that current loss of longevity
      advantage in Okinawa is a result of diet westernization and that the dietary
      restriction is a valid way of life extension in humans.

PMID- 21893947
TI  - Early intensive obstetric and medical nutrition care is associated with decreased
      prepregnancy obesity impact on perinatal outcomes.
AB  - BACKGROUND/AIMS: To compare the gestational weight gain and adverse perinatal
      outcomes in urban Mexican women with prepregnancy overweight or obesity, under an
      early intensive obstetric and nutrition program versus women with prepregnancy
      normal weight. METHODS: A cohort of 546 pregnant women with prepregnancy normal
      weight (n = 201, NW), overweight (n = 171, OW) or obesity (n = 174, OB), <=13
      weeks of gestation and a singleton pregnancy. OW and OB groups were under early
      intensive obstetric and nutritional care and NW group was under routine prenatal
      care. Miscarriage, hypertensive disorders, premature rupture of membranes,
      preterm birth, stillbirth, gestational diabetes mellitus (GDM) and large- or
      small-for-gestational-age newborns, were compared between groups. RESULTS: Weight
      gain was smaller in OB than in OW or NW (mean +/- SD): 6.1 +/- 4.4, 9.5 +/- 5.1,
      10.3 +/- 5.4 kg, respectively (p < 0.001). OB women had the highest frequency of
      GDM (p < 0.001), lack of spontaneous labor (p < 0.001) and preeclampsia (p <
      0.001), but no other between-group differences existed. CONCLUSION: Early
      intensive medical-nutrition prenatal care and adequate gestational weight gain
      may contribute to decreasing most maternal and newborn adverse outcomes
      associated with prepregnancy overweight or obesity.

PMID- 21893948
TI  - Prenatal bystander stress alters brain, behavior, and the epigenome of developing
      rat offspring.
AB  - The prenatal environment, including prenatal stress, has been extensively studied
      in laboratory animals and humans. However, studies of the prenatal environment
      usually directly stress pregnant females, but stress may come 'indirectly',
      through stress to a cage-mate. The current study used indirect prenatal bystander
      stress and investigated the effects on the gross morphology, pre-weaning
      behavior, and epigenome of rat offspring. Pregnant Long-Evans rats were housed
      with another female rat that underwent elevated platform stress from gestational
      days 12 to 16. We found that ultrasonic vocalizations of female cage-mates were
      disrupted following the stress procedure. After birth, offspring were tested on
      two behavioral tasks and sacrificed at postnatal day 21 (p21). Frontal cortex and
      hippocampal tissue was used to measure global DNA methylation and gene expression
      changes. At p21, bystander-stressed female offspring exhibited increased body
      weight. Offspring behavior on the negative geotaxis task was altered by prenatal
      bystander stress, and locomotor behavior was reduced in female offspring. Global
      DNA methylation increased in the frontal cortex and hippocampus of bystander
      stressed offspring. Microarray analysis revealed significant gene expression
      level changes in 558 different genes, of which only 10 exhibited overlap between
      males and females or brain areas. These alterations in gene expression were
      associated with overrepresentation of 36 biological processes and 34 canonical
      pathways. Prenatal stress thus does not have to be experienced by the mother
      herself to influence offspring brain development. Furthermore, this type of
      'indirect' prenatal stress alters offspring DNA methylation patterns, gene
      expression profiles, and behavior.

PMID- 21893950
TI  - Kaposi's sarcoma restricted to an immunocompromised district.

PMID- 21893949
TI  - What can we learn about autism from studying fragile X syndrome?
AB  - Despite early controversy, it is now accepted that a substantial proportion of
      children with fragile X syndrome (FXS) meets diagnostic criteria for autism
      spectrum disorder (ASD). This change has led to an increased interest in studying
      the association of FXS and ASD because of the clinical consequences of their co
      occurrence and the implications for a better understanding of ASD in the general
      population. Here, we review the current knowledge on the behavioral,
      neurobiological (i.e., neuroimaging), and molecular features of ASD in FXS, as
      well as the insight into ASD gained from mouse models of FXS. This review covers
      critical issues such as the selectivity of ASD in disorders associated with
      intellectual disability, differences between autistic features and ASD diagnosis,
      and the relationship between ASD and anxiety in FXS patients and animal models.
      While solid evidence supporting ASD in FXS as a distinctive entity is emerging,
      neurobiological and molecular data are still scarce. Animal model studies have
      not been particularly revealing about ASD in FXS either. Nevertheless, recent
      studies provide intriguing new leads and suggest that a better understanding of
      the bases of ASD will require the integration of multidisciplinary data from FXS
      and other genetic disorders.

PMID- 21893952
TI  - Incretin receptors in non-neoplastic and neoplastic thyroid C cells in rodents
      and humans: relevance for incretin-based diabetes therapy.
AB  - While incretins are of great interest for the therapy of diabetes 2, the focus
      has recently been brought to the thyroid, since rodents treated with glucagon
      like peptide-1 (GLP-1) analogs were found to occasionally develop medullary
      thyroid carcinomas. Incretin receptors for GLP-1 and glucose-dependent
      insulinotropic polypeptide (GIP) were therefore measured in various rodent and
      human thyroid conditions. In vitro GLP-1 and GIP receptor autoradiography were
      performed in normal thyroids, C-cell hyperplasia and medullary thyroid carcinomas
      in rodents. Receptor incidence and density were assessed and compared with the
      receptor expression in human thyroids, medullary thyroid carcinomas, and TT
      cells. GLP-1 receptors are expressed in C cells of normal rat and mice thyroids.
      Their density is markedly increased in rat C-cell hyperplasia and medullary
      thyroid carcinomas, where their incidence amounts to 100%. GIP receptors are
      neither detected in normal rodent thyroids nor in C-cell hyperplasia, but are
      present in all rat medullary thyroid carcinomas. No GLP-1 or GIP receptors are
      detected in normal human thyroids. Whereas only 27% of all human medullary
      thyroid carcinomas express GLP-1 receptors, up to 89% express GIP receptors in a
      high density. TT cells lack GLP-1 receptors but express GIP receptors. GLP-1
      receptors are frequently expressed in non-neoplastic and neoplastic C cells in
      rodents while they are rarely detected in human C-cell neoplasia, suggesting
      species differences. Conversely, GIP receptors appear to be massively
      overexpressed in neoplastic C cells in both species. The presence of incretin
      receptors in thyroid C cell lesions suggests that this organ should be monitored
      before and during incretin-based therapy of diabetes.

PMID- 21893953
TI  - Modified external ventricular drainage in pediatric tuberculous meningitis: is it
      possible to avoid ventriculoperitoneal shunt placement?
AB  - OBJECTIVE: Ventriculoperitoneal shunting is the current mainstay of treatment for
      children with tuberculous meningitis with hydrocephalus. However,
      ventriculoperitoneal shunting is highly associated with complications, and more
      importantly, long-term, indwelling shunt devices may adversely affect children's
      spirits and psychological health. Therefore, there is clearly a need to explore
      methods of CSF diversion to avoid ventriculoperitoneal shunting. METHODS: We
      studied 6 cases of children with tuberculous meningitis with hydrocephalus in
      whom external drainage from the ventricle to the subcutaneous abdomen was
      adopted. Outcomes were assessed over a 6- to 9-month follow-up period based on
      improvements in radiological features, such as ventricular morphology, as well as
      the need for ventriculoperitoneal shunting and any complications. RESULTS: The
      drainage tubes were removed in 4 cases 4-6 months after the modified external
      ventricular drainage surgery, and 2 patients went on to receive a
      ventriculoperitoneal shunt. All patients' CSF protein and cell counts returned to
      normal, and imaging showed improved ventricular morphology and no intracranial
      secondary infection. CONCLUSION: In our preliminary study, the modified
      ventricular drainage device can produce satisfactory outcomes and relatively safe
      effects and may help some patients to avoid ventriculoperitoneal shunt placement.

PMID- 21893954
TI  - Moyamoya syndrome after radiation therapy: case reports.
AB  - Potentially harmful effects of irradiation on the developing central nervous
      system have been well documented. We report 2 pediatric patients with moyamoya
      syndrome developed after irradiation. CASE: A 3-year-old girl had received 4,860
      cGy of postoperative radiation for optic pathway glioma. Cerebral angiography 7
      months after completion of the radiation therapy revealed progressive cerebral
      arterial occlusive disease, involving the internal carotid artery on either side
      of the circle of Willis, with abnormal netlike vessels. Another 5-year-old girl
      had received 3,600 cGy of postoperative radiation on the cerebrum for a
      medulloblastoma. Two years later, she was diagnosed with moyamoya syndrome and
      treated with indirect revascularization. She died due to further progressive
      obstruction of the right M1 and A1 on the unoperated hemisphere, in spite of well
      developed collateral circulation from the superficial temporal artery and middle
      meningeal artery on the operated left hemisphere. We suggest that radiation
      therapy with portals typically including carotid siphon may particularly cause
      vascular damage, regardless of the tumor pathology and lead to radiation-induced
      moyamoya syndrome. The prognosis may be poorer in case of poor collateral flow
      and rapid progression. The radiation therapy may cause fatal vascular damage so
      it should be taken into consideration when a treatment plan is being formulated
      for young patients.

PMID- 21893955
TI  - Focal intradural brain infections in children: an analysis of management and
      outcome.
AB  - INTRODUCTION: Focal intradural infections of the brain include empyema and
      abscess in the supratentorial and infratentorial spaces. These are amenable to
      surgical management. Various other issues may complicate the course of
      management, e.g. hydrocephalus with infratentorial lesions or cortical venous
      thrombosis with supratentorial lesions. Here, we review the management and
      identify factors affecting outcome in these patients. MATERIALS AND METHODS: This
      is a retrospective analysis of all children (aged <18 years) treated at the
      National Institute of Mental Health and Neurosciences, Bangalore, India, between
      1988 and 2004. Case records were analyzed to obtain clinical, radiological,
      bacteriological and follow-up data. RESULTS: There were 231 children who
      underwent treatment for focal intradural abscess/empyema at our institute. These
      included 57 children with cerebral abscess, 65 with supratentorial empyema, 82
      with cerebellar abscess and 27 with infratentorial empyema. All patients
      underwent emergency surgery (which was either burr hole and aspiration of the
      lesion or craniotomy/craniectomy and excision/evacuation), along with antibiotic
      therapy, typically 2 weeks of intravenous and 4 weeks of oral therapy. The
      antibiotic regimen was empiric to begin with and was altered if any sensitivity
      pattern of the causative organism(s) could be established by culture.
      Hydrocephalus was managed with external ventricular drainage initially and with
      ventriculoperitoneal shunt if warranted. Mortality rates were 4.8% for cerebral
      abscess, 9.6% for cerebellar abscess, 10.8% for supratentorial subdural empyema
      and 3.7% for posterior fossa subdural empyema. The choice of surgery was found to
      have a strong bearing on the recurrence rates and outcome in most groups, with
      aggressive surgery with craniotomy leading to excellent outcomes with a low
      incidence of residual/recurrent lesions. CONCLUSIONS: Antibiotic therapy,
      emergency surgery and management of associated complications are the mainstays of
      treatment of these lesions. We strongly advocate early, aggressive surgery with
      antibiotic therapy in children with focal intradural infections.

PMID- 21893956
TI  - Postoperative extra-axial cerebrospinal fluid collection--its pathophysiology and
      clinical management.
AB  - OBJECTIVE: External hydrocephalus, introduced by Dandy and Blackfan in 1914 [Am J
      Dis Child 1914;8:406-482], is used to describe the clinical condition of
      cerebrospinal fluid (CSF) accumulation in the subarachnoid space with its space
      expansion and increased intracranial pressure in pediatric patients. Benign
      subdural effusion, subdural hygroma and pseudohydrocephalus are some terms used
      to describe some conditions, not clearly defined at the moment as separate
      pathological entities. We report 3 pediatric cases which had CSF collections
      after craniotomy. Neuroimaging investigations revealed CSF collection after
      surgery. All 3 cases had a poor clinical course with resolution after shunting.
      This report analyzes the mechanisms and pathophysiology of postoperative extra
      axial CSF collections (PECC), indicating that CSF accumulations in the extra
      axial spaces (inside or outside the arachnoid) after surgery have a common
      pathophysiology. Therefore, the treatment protocol can be specific. PATIENTS:
      Three pediatric cases, aged from 11 months to 6 years, had large tumors located
      from their suprasellar region to the hypothalamus and third ventricle. The tumors
      were excised surgically through either an anterior interhemispheric translamina
      terminalis or a transsylvian translamina-terminalis approach or both. The surgery
      conducted created a wide opening of the anterior interhemispheric or the sylvian
      fissures, dissecting the lamina terminalis and Liliequist's membrane resulting in
      a new artificial CSF tract from the basal cisterns to the subdural space.
      Clinical symptoms such as deterioration of consciousness level developed within a
      few weeks after surgery, and a follow-up computed tomography image confirmed
      subdural CSF collection. Symptoms improved after ventriculoperitoneal (V-P)
      shunting. DISCUSSION: External hydrocephalus, subdural effusion and the other
      entities mentioned above are frequently observed in children, and little is known
      about their pathophysiology. To differentiate from the whole entity of CSF
      accumulation within the subdural and subarachnoid space, we use the term PECC to
      specify the main pathophysiological condition resulting from a wide dissection
      and opening of the arachnoid membrane and communication with the basal cisterns.
      CONCLUSION: We present the occurrence of CSF collections in the extra-axial space
      after surgery as the specific condition of PECC. Broadly dissecting the arachnoid
      membrane, with a communication remaining with the ventricles, is the main factor
      contributing to PECC, and patients have shown that V-P shunting is an effective
      procedure preventing progression and effectively treating PECC.

PMID- 21893957
TI  - Meningioangiomatosis in a 5-year-old boy presenting with intractable seizures.
AB  - A 5-year-old boy with a history of epilepsy underwent brain magnetic resonance
      imaging (MRI) because of an increase in seizure frequency. Brain MRI demonstrated
      a left frontal lesion. The patient was operated upon, and gross total excision
      was performed. The histological diagnosis was meningioangiomatosis. On follow-up
      examination 10 years later, the patient was free of seizures and without any
      evidence of tumor recurrence. Meningioangiomatosis is a rare benign hamartomatous
      lesion that is associated with seizures. Complete excision is associated with
      favorable long-term outcome. The novelty of the present case is the young age of
      the child at presentation and the curative role of surgery considering the long
      term follow-up.

PMID- 21893958
TI  - Quality of health care of rosacea in Germany from the patient's perspective:
      results of the national health care study Rosareal 2009.
AB  - OBJECTIVES: To obtain reliable data on quality of care of rosacea and to compare
      care indicators with those found in atopic dermatitis and psoriasis. PATIENTS AND
      METHODS: In this cross-sectional study, clinical history, health-related quality
      of life (HrQoL), medication and treatment benefit of patients with rosacea were
      assessed by standardized questionnaires. Data were compared to patients with
      atopic dermatitis and psoriasis. RESULTS: Almost all 475 participants (96.4%) had
      received topical therapy. 24% had used cortisone ointments. The mean Dermatology
      Life Quality Index (DLQI) was 4.3 +/- 4.6 (atopic dermatitis: 8.5 +/- 6.0,
      psoriasis: 6.7 +/- 6.2). The Patient Benefit Index (patient-defined therapeutic
      benefit) was 1.9 +/- 1.2 (psoriasis: 2.3 +/- 1.1, atopic dermatitis: 2.1 +/-
      1.1). CONCLUSIONS: Only a small proportion of the rosacea patients had
      substantial impairments in HrQoL. Overall, their burden appears to be lower than
      in patients with atopic dermatitis or psoriasis. However, the lower therapeutic
      benefit and the high proportion of topical steroid use indicate a need for
      optimized therapy.

PMID- 21893959
TI  - The first description of the hair follicle bulge by Franz von Leydig.

PMID- 21893961
TI  - Array CGH in human leukemia: from somatics to genetics.
AB  - During the past decade, array CGH has been applied to study copy number
      alterations in the genome in human leukemia in relation to prediction of
      prognosis or responsiveness to therapy. In the first segment of this review, we
      will focus on the identification of acquired mutations by array CGH, followed by
      studies on the pathogenesis of leukemia associated with germline genetic
      variants, phenotypic presentation and response to treatment. In the last section,
      we will discuss constitutional genomic aberrations causally related to myeloid
      leukemogenesis.

PMID- 21893960
TI  - Insufficient and incomplete shaving in chronic venous leg ulcers leads to a poor
      prognosis of the skin graft: a histomorphological analysis.
AB  - BACKGROUND: The surgical treatment for therapy-resistant venous leg ulcers is
      shave therapy with mesh graft transplantation. OBJECTIVE: To demonstrate the need
      of complete shaving with help of histomorphological criteria. METHODS: Biopsies
      were taken from the bottom and the border of the 28 ulcers and from nonulcer skin
      nearby. Specimens were analyzed in correlation to the clinical course 6 months
      after the treatment (healed/nonhealed/recurrent). RESULTS: 10 ulcers healed, 10
      were recurrent and 8 nonhealed. Nonhealed ulcers had an increased broadening of
      collagen fibers and rete ridges and reduced elastic fibers at the border of the
      ulcer. Significantly more obliterated vessels were in the upper dermis at the
      border of the nonhealed ulcers. Recurrent ulcers showed more signs of
      dermatoliposclerosis. CONCLUSION: In nonhealed and recurrent ulcers
      histomorphological aspects of dermatoliposclerosis are still detectable. Thus, a
      more extensive fibrosis seems to be associated with a poorer outcome. The
      hypothesis that possibly a more aggressive shave therapy can increase the healing
      rate should be verified in a prospective study.

PMID- 21893962
TI  - Rorgammat+ innate lymphoid cells in intestinal homeostasis and immunity.
AB  - Innate lymphoid cells (ILC) combine innate and adaptive immune functions and are
      part of the first line of defense against mucosal infections. ILC are set apart
      from adaptive lymphocytes by their independence on RAG genes and the resulting
      absence of specific antigen receptors. In this review, we will discuss the
      biology and function of intestinal ILC that express the nuclear hormone receptor
      Rorgammat (encoded by the Rorc gene) and highlight their role in intestinal
      homeostasis and immunity.

PMID- 21893963
TI  - Difficulty in inserting 25- and 23-gauge trocar cannula during vitrectomy.
AB  - PURPOSE: To determine the incidence of difficulty in inserting a 25- and 23-gauge
      trocar cannula (DITC) during 25- or 23-gauge micro-incision vitrectomy surgery
      (MIVS). METHODS: Retrospective, consecutive, interventional case series performed
      by a single surgeon at a single centre. We defined a DITC as the condition where
      at least 1 trocar cannula could not be inserted into the vitreous at the
      beginning of MIVS. The incidence of DITC was calculated from 1,525 eyes, and the
      pre-operative demographics of the DITC cases were compared to those of the non
      DITC cases. RESULTS: The incidence of DITC for all cases was 0.6% (9 of 1,525
      eyes). Overall, there were 242 eyes with a retinal detachment (RD), and 8 of the
      9 eyes with DITC had an RD with an incidence of 3.3% (8 of 242 RD eyes). Seven of
      these 8 eyes had a total RD, 4 also had a choroidal detachment, 4 eyes were also
      myopic (>-8.0 dpt, high myopia), and 6 of the 8 eyes were hypotonic (<8 mm Hg).
      The DITC cases had larger RDs (p<0.0001), a higher incidence of choroidal
      detachment (p<0.0001), higher myopia (p=0.0204) and hypotony (p=0.0003) than the
      non-DITC eyes with an RD. CONCLUSIONS: A large RD, a choroidal detachment, high
      myopia and hypotony are significant risk factors for DITC. We recommend that MIVS
      should be performed cautiously for eyes with these risk factors.

PMID- 21893965
TI  - Two-year results of photodynamic therapy combined with intravitreal anti-vascular
      endothelial growth factor for polypoidal choroidal vasculopathy.
AB  - BACKGROUND/AIMS: To evaluate the 2-year efficacy of photodynamic therapy (PDT)
      combined with intravitreal injection of anti-vascular endothelial growth factor
      (anti-VEGF) in patients with polypoidal choroidal vasculopathy (PCV). METHODS:
      Twenty-two eyes of 22 patients with PCV followed up for >=24 months after PDT and
      anti-VEGF combination therapy were retrospectively reviewed. The patients
      received intravitreal anti-VEGF (1.25 mg bevacizumab or 0.5 mg ranibizumab)
      within 7 days after PDT. Eyes were retreated with PDT and anti-VEGF injection, or
      with only anti-VEGF injection, when indicated. Main outcome measures were best
      corrected visual acuity (BCVA) and central foveal thickness (CFT). RESULTS: The
      mean baseline BCVA (0.43+/-0.33 logarithm of the minimum angle of resolution,
      logMAR) was 0.28+/-0.24 at 12 months (p<0.05 vs. baseline) and 0.39+/-0.28 at 24
      months (not significant). At 24 months, BCVA improved by >=0.3 logMAR in 27.3% of
      the eyes, did not significantly decrease in 59.1%, and decreased by >=0.3 logMAR
      in 13.6%. The mean CFT was 269.4+/-134.5 MUm at baseline and significantly
      decreased to 139.6+/-45.8 MUm (12 months) and 199.6+/-72.9 MUm (24 months). PDT
      was administered 1.45+/-0.86 times and anti-VEGF injected 4.45+/-1.36 times over
      the 24-month period. CONCLUSION: Combined PDT and anti-VEGF injection were
      effective for 2 years in PCV patients. Visual acuity significantly improved
      during year 1, but the benefit diminished in year 2. Further investigations are
      required to determine how to prolong the therapeutic effect of combination
      therapy for PCV.

PMID- 21893964
TI  - Bacterial heat shock protein 60, GroEL, can induce the conversion of naive T
      cells into a CD4 CD25(+) Foxp3-expressing phenotype.
AB  - Recent publications report that heat shock proteins (HSPs) can endow regulatory
      responses to the systemic immune system when administered via the mucosal route,
      leading to an amelioration of atherosclerosis and allergy. However, it remains
      poorly understood if HSP antigens exist in the luminal contents of the
      gastrointestinal tract and which types of HSP induce regulatory responses. Here
      we addressed these problems, considering that numerous gut microflora and foods
      are natural sources of HSPs. SDS-PAGE and immunoblotting with the anti-HSP60
      antibody demonstrated the intact and degraded forms of HSP60 mainly in appendix
      and large intestine of the gastrointestinal tract. No reactivity with this
      antibody was observed for any of the luminal contents derived from germ-free
      animals, suggesting gut microflora to be a source of the intestinal HSPs because
      of lack of HSPs in animal chow diet. GroEL, a typical member of bacterial HSP60,
      showed a tendency to stimulate splenocytes in germ-free mice, compared to that in
      conventional mice, suggesting that resident commensal bacterial GroEL may
      stimulate HSP-reactive T cells as regulatory cells in conventional animals.
      Importantly, GroEL, but not mouse-derived HSP60, caused naive T cells to
      differentiate into CD4(+) CD25(+) Foxp3(+) T cells, indicating that the
      production of regulatory T cells depends on the type of HSP. Thus, HSPs derived
      from commensal microbes can be utilized to stimulate immunoregulatory pathways
      for the maintenance of intestinal homeostasis.

PMID- 21893966
TI  - Pre- and postnatal ultrasound and magnetic resonance imaging of intracranial
      extra-axial glioneuronal heterotopia.
AB  - Glioneuronal heterotopias are rare malformations composed of differentiated
      derivates of neuroectodermal tissue that include disorganized neuronal and glial
      cells. They are typically located extracranially. The nasal cavity represents the
      most common location. Glioneuronal heterotopias have also been reported in the
      orbit, pharynx, middle ear, neck and thorax. Rarely, glioneuronal heterotopias
      may be located intracranially. We are aware of only 15 patients reported with
      intracranial extra-axial glioneuronal heterotopia (IEGH). We present the prenatal
      ultrasound and MRI as well as the matching postnatal CT, conventional MRI and
      diffusion tensor imaging findings of a newborn with an infratentorial IEGH
      accompanied with craniofacial anomalies.

PMID- 21893968
TI  - Phosphorylation of histone H3S10 in animal chromosomes: is there a uniform
      pattern?
AB  - Phosphorylation of serine 10 in histone H3 (H3S10ph) has been extensively
      analyzed and appears to be a conserved chromatin change associated with
      chromosome condensation in different eukaryotic organisms. In this work, we
      report the distribution of H3S10ph during meiosis in monocentric and holokinetic
      chromosomes of 6 insect species and in mitotic chromosomes of 7 mammalian
      species, aiming to investigate the labeling patterns in phylogenetically distant
      groups. The results indicated a very similar phosphorylation timing and
      distribution pattern among insects. The sex chromosomes of insects analyzed were
      always undercondensed and hypophosphorylated. Similarly, the micro chromosomes of
      the bug Pachylis aff pharaonis were also undercondensed and hypophosphorylated.
      Holokinetic chromosomes of bugs and monocentric chromosomes of grasshoppers and
      beetles displayed identical phosphorylation pattern in spite of the difference in
      the centromere type. Among mammals, a uniform chromosome phosphorylation was
      observed in marsupials, whereas bat chromosomes displayed a longitudinal banding
      pattern. These data indicate that, in general, the intensity of H3S10
      phosphorylation in animal chromosomes is variable among the distinct chromosome
      types and associated with the degree of chromatin condensation at metaphase, but
      it may vary between different groups of animals.

PMID- 21893967
TI  - On the promise of pharmacotherapies targeted at cognitive and neurodegenerative
      components of Down syndrome.
AB  - Down syndrome (DS) is the phenotypic consequence of trisomy 21 and is the most
      common genetically defined cause of intellectual disability. The most complete,
      widely available, and well-studied animal model of DS is the Ts65Dn mouse. Recent
      preclinical successes in rescuing learning and memory deficits in Ts65Dn mice are
      legitimate causes for optimism that pharmacotherapies for cognitive deficits in
      DS might be within reach. This article provides a snapshot of potential
      pharmacotherapies for DS, with emphasis on our recent results showing that the N
      methyl-D-aspartate receptor antagonist memantine can reverse learning and memory
      deficits in Ts65Dn mice. Because memantine has already been approved for the
      therapy of Alzheimer's dementia, we have been able to very rapidly translate
      these results into human research and are currently conducting a 16-week,
      randomized, double-blind, placebo-controlled evaluation of the efficacy,
      tolerability and safety of memantine hydrochloride on enhancing the cognitive
      abilities of young adults with DS. The design and current status of this clinical
      trial will be discussed, which will be followed by some speculation on the
      potential impact of this and future clinical trials in the field of DS.

PMID- 21893969
TI  - Hypospadias in a male (78,XY; SRY-positive) dog and sex reversal female (78,XX;
      SRY-negative) dogs: clinical, histological and genetic studies.
AB  - Hypospadias is rarely reported in dogs. In this study we pre-sent 2 novel cases
      of this disorder of sexual development and, in addition, a case of hereditary sex
      reversal in a female with an enlarged clitoris. The first case was a male Moscow
      watchdog with a normal karyotype (78,XY) and the presence of the SRY gene. In
      this dog, perineal hypospadias, bilateral inguinal cryptorchidism and testes were
      observed. The second case, representing the Cocker spaniel breed, had a small
      penis with a hypospadic orifice of the urethra, bilateral cryptorchidism, testis
      and a rudimentary gonad inside an ovarian bursa, a normal female karyotype
      (78,XX) and a lack of the SRY gene. This animal was classified as a compound sex
      reversal (78,XX, SRY-negative) with the hypospadias syndrome. The third case was
      a Cocker spaniel female with an enlarged clitoris and internally located
      ovotestes. Cytogenetic and molecular analyses revealed a normal female karyotype
      (78,XX) and a lack of the SRY gene, while histology of the gonads showed an
      ovotesticular structure. This case was classified as a typical hereditary sex
      reversal syndrome (78,XX, SRY-negative). Molecular studies were focused on coding
      sequences of the SRY gene (case 1) and 2 candidates for monogenic hypospadias,
      namely MAMLD1 (mastermind-like domain containing 1) and SRD5A2 (steroid-5-alpha
      reductase, alpha polypeptide 2). Sequencing of the entire SRY gene, including 5'-
      and 3'-flanking regions, did not reveal any mutation. The entire coding sequence
      of MAMLD1 and SRD5A2 was analyzed in all the intersexes, as well as in 4
      phenotypically normal control dogs (3 females and 1 male). In MAMLD1 2 SNPs,
      including 1 missense substitution in exon 1 (c.128A>G, Asp43Ser), were
      identified, whereas in SRD5A2 7 polymorphisms, including 1 missense SNP
      (c.358G>A, Ala120Thr), were found. None of the identified polymorphisms
      cosegregated with the intersexual phenotype, thus, we cannot confirm that
      hypospadias may be associated with polymorphism in the coding sequence of the
      studied genes.

PMID- 21893970
TI  - Preventive scleral buckling and silicone oil tamponade are important for
      posttraumatic endophthalmitis successfully managed with vitrectomy.
AB  - AIMS: Posttraumatic endophthalmitis (PTE) managed with pars plana vitrectomy
      (PPV) and a variety of other methods often resulted in retinal detachment (RD),
      which deteriorates postoperative visual acuity (VA). We investigated initial
      ocular conditions, surgical management and outcomes of PTE patients and analyzed
      their relationship in order to find the necessary management for different
      patients' conditions. METHODS: Retrospective study. Medical records of 62
      consecutive patients who were diagnosed with PTE and managed with PPV were
      retrospectively analyzed. The included patients were divided into two groups
      depending on their initial VA, with light perception (LP) as borderline: group A
      (12 cases; VA=LP) and group B (50 cases; VA>LP). Specific variables related to
      surgical outcomes were analyzed, including: initial VA; intraocular foreign body;
      location and length of the wound; microbiologic test; cataract extraction;
      scleral buckling; silicon oil tamponade; gas tamponade, and retinal restoration.
      Data were statistically analyzed by the chi2 test, by univariate analysis for
      predictors and by multivariate logistic regression analysis. RESULTS: RD happened
      in 19 (30.6%) of the 62 cases included. There were 6 cases (50%) in group A and
      13 cases (26%) in group B which resulted in RD. Statistical analysis demonstrated
      that none of the related factors were correlated to the occurrence of RD (all
      factors: p>0.05) in group A, but in group B, scleral buckling (with: 2/22, 9%;
      without: 11/28, 39%; p<0.05) and silicone oil tamponade (with: 0/6; without:
      13/44, 30%; p<0.05) were statistically significantly correlated to the occurrence
      of RD. CONCLUSIONS: Preventive scleral buckling and silicone oil tamponade are
      important for patients with good initial VA (VA>LP) to be successfully managed by
      PPV.

PMID- 21893971
TI  - Ultrastructure of the membrana limitans interna after dye-assisted membrane
      peeling.
AB  - The purpose of this study was to investigate the ultrastructure of the membrana
      limitans interna (internal limiting membrane, ILM) and to evaluate alterations to
      the retinal cell layers after membrane peeling with vital dyes. Twenty-five
      patients (25 eyes) who underwent macular hole surgery were included, whereby 12
      indocyanine green (ICG)- and 13 brilliant blue G (BBG)-stained ILM were analyzed
      using light, transmission electron and scanning electron microscopy. Retinal cell
      fragments on the ILM were identified in both groups using immunohistochemistry.
      Comparing ICG- and BBG-stained membranes, larger cellular fragments were observed
      at a higher frequency in the BBG group. Thereby, the findings indicate that ICG
      permits an enhanced separation of the ILM from the underlying retina with less
      mechanical destruction. A possible explanation might be seen in the known
      photosensitivity of ICG, which induces a stiffening and shrinkage of the ILM but
      also generates retinal toxic metabolites.

PMID- 21893972
TI  - Comparison of grid laser, intravitreal triamcinolone, and intravitreal
      bevacizumab in the treatment of diffuse diabetic macular edema.
AB  - PURPOSE: To compare the effects of grid laser (GL), intravitreal bevacizumab
      (IVB), and intravitreal triamcinolone acetonide (IVTA) in diffuse diabetic
      macular edema (DDME). PROCEDURES: One hundred and twenty-six patients (126 eyes)
      treated with GL (modified grid), IVTA (4 mg), and IVB (1.25 mg) injections,
      matched for best corrected visual acuity (BCVA) and OCT-based central macular
      thickness at presentation, were enrolled. Primary outcome measure was change in
      best corrected logMAR visual acuity at 1-year follow-up. RESULTS: Rates of visual
      stabilization (within +/-0.2 logMAR of baseline BCVA) (71.4, 83.3, 78.6%,
      respectively) were not different between the groups (p = 0.41) at 12-month follow
      up. Higher rates of anatomical and functional success, however, were evident in
      IVB and IVTA groups within 6 months of treatment (p < 0.05 for both). No severe
      adverse effects except higher intraocular pressure (10 mm Hg from baseline) in
      one third (14 eyes) of the IVTA cases, who required trabeculectomy in 2 (4.8%)
      eyes, were observed. CONCLUSIONS: Intraocular injections may give favorable
      results within the first 6 months, and after 6 months, GL results seem to be more
      favorable in the treatment of treatment-naive, acute, nonischemic, and center
      involving DDME.

PMID- 21893973
TI  - IL-1 inhibition in cryopyrin-associated periodic syndrome and beyond: a million
      dollar question about the injection schedule of biotherapies.

PMID- 21893974
TI  - Reduced serum fetuin-A in nephrotic children: a consequence of proteinuria?
AB  - BACKGROUND: The extracellular protein fetuin-A is a potent soluble inhibitor of
      calcification, and its deficiency has been associated with vascular calcification
      in dialysis patients. In proteinuric patients, significant urinary losses of
      fetuin-A may cause low serum fetuin-A levels. METHODS: In a cross-sectional
      study, urinary/serum concentrations of fetuin-A were investigated in proteinuric
      children with glomerular diseases and preserved renal function (n = 58) in
      comparison to healthy controls (n = 246). RESULTS: Mean fetuin-A serum
      concentrations were clearly reduced in children with nephrotic syndrome (0.25 +/-
      0.14 g/l, p < 0.001), slightly reduced in children with large proteinuria (0.39
      +/- 0.15 g/l, p < 0.05), and comparable to controls in those with mild
      proteinuria (0.45 +/- 0.14 vs. 0.46 +/- 0.12 g/l). Fetuin-A was positively
      correlated with serum protein (r = 0.58), albumin (r = 0.57), and calcium (r =
      0.64), but negatively correlated with proteinuria (r = -0.41), albuminuria (r = 
      0.46), and urinary fetuin-A excretion (r = -0.48; each p < 0.001). The fractional
      excretion of fetuin-A was significantly associated with the degree of proteinuria
      and serum fetuin-A levels. However, the urinary loss of fetuin-A and albumin in
      nephrotic children differed by three orders of magnitude and the mean fractional
      excretion of fetuin-A was only 1/10 of that of albumin (0.016 +/- 0.029 vs. 0.162
      +/- 0.403%; p < 0.001). CONCLUSIONS: Fetuin-A is clearly reduced in children with
      nephrotic syndrome and associated with the degree of hypoalbuminemia. This is due
      to urinary fetuin-A loss and/or reduced hepatic synthesis. Persistent fetuin-A
      deficiency may have an impact on cardiovascular morbidity in nephrotic children.

PMID- 21893975
TI  - Epidemiology of interdialytic ambulatory hypertension and the role of volume
      excess.
AB  - BACKGROUND: The epidemiology of hypertension among hemodialysis (HD) patients is
      difficult to describe accurately because of difficulties in the assessment of
      blood pressure (BP). METHODS: Using 44-hour interdialytic ambulatory BP
      measurements, we describe the epidemiology of hypertension in a cohort of 369
      patients. To seek correlates of hypertension control, antihypertensive agents
      were withdrawn among patients with controlled hypertension and ambulatory BP
      monitoring was repeated. RESULTS: Hypertension (defined as an average ambulatory
      systolic BP >=135 mm Hg or diastolic BP >=85 mm Hg, or the use of
      antihypertensive medications) was prevalent in 82% of the patients and
      independently associated with epoetin use, lower body mass index and fewer years
      on dialysis. Although 89% of the patients were being treated, hypertension was
      controlled adequately in only 38%. Poor control was independently associated with
      greater antihypertensive drug use. Inferior vena cava (IVC) diameter in
      expiration was associated with increased risk of poorly controlled hypertension
      both in cross-sectional analysis and after withdrawal of antihypertensive drugs.
      CONCLUSIONS: Interdialytic hypertension is highly prevalent and difficult to
      control among HD patients. End-expiration IVC diameter is associated with poor
      control of hypertension in cross-sectional analyses as well as after washout of
      antihypertensive drugs. Among HD patients, an attractive target for improving
      hypertension control appears to be the reduction of extracellular fluid volume.

PMID- 21893976
TI  - A new endotoxin adsorber in septic shock: observational case series.
AB  - AIMS: Effects of a new endotoxin adsorber on the length of noradrenaline (NA)
      treatment, LPS (lipopolysaccharide) levels and SOFA (sequential organ failure
      assessment) scores in septic shock were evaluated. METHODS: Two-hour
      hemoperfusion with LPS adsorber was initiated in patients with septic shock and
      endotoxemia. Controls were matched for age, focus and severity of illness.
      RESULTS: Adsorption treatment (n = 9) exhibited a significant decrease in EAA
      (endotoxin activity assay) activity (0.55 [0.44-0.68] vs. 0.25 [0.13-0.41], p =
      0.019) and NA infusion rate (0.217 MUg/kg/min [0.119-0.0508] vs. 0 MUg/kg/min [0
      0.09], p = 0.026) from pretreatment to 24 h post-treatment. The median decrease
      in SOFA scores from pretreatment to 24 h was 3.0 points (1.5-4.5), p = 0.002.
      Duration of NA infusion was significantly shorter compared to controls (39 h [31
      48] vs. 54 h [43-151], p = 0.03). CONCLUSIONS: LPS adsorber treatment was
      associated with a decrease in NA dose, decrease in SOFA scores and LPS
      concentrations.

PMID- 21893977
TI  - Reduction in serum high mobility group box-1 level by polymyxin B-immobilized
      fiber column in patients with idiopathic pulmonary fibrosis with acute
      exacerbation.
AB  - BACKGROUND/AIM: Recent reports suggest that polymyxin B (PMX)-immobilized fiber
      may have beneficial effects in idiopathic pulmonary fibrosis (IPF) with acute
      exacerbation (AE). High mobility group box-1 (HMGB-1) is an important pro
      inflammatory mediator that contributes to acute lung inflammation. This study was
      aimed to investigate whether PMX treatment affects serum HMGB-1 levels and
      oxygenation in IPF patients with AE. MATERIALS AND METHODS: Twenty IPF patients
      with AE were treated by PMX. PMX treatment was carried out once daily for 2
      successive days. Serum HMGB-1 levels were measured before and after PMX
      treatment. We also monitored arterial oxygen tension (PaO(2))/inspiratory oxygen
      fraction (FiO(2)) (P/F) ratio. PMX fiber columns were analyzed to examine whether
      HMGB-1 was absorbed by PMX. RESULTS: PMX treatment significantly improved both
      the serum HMGB-1 level and P/F ratio. HMGB-1 was detected in washing medium from
      the PMX column. CONCLUSION: PMX treatment may reduce serum HMGB-1 and improve
      oxygenation in patients with IPF with AE.

PMID- 21893978
TI  - Genetic variants in the promoter region of the ALOX5AP gene and susceptibility of
      ischemic stroke.
AB  - BACKGROUND: Despite accumulating evidence supporting the association between
      variants of the ALOX5AP gene and atherosclerotic vascular events, the precise
      mechanism is still unclear. No variants in the coding sequence that lead to amino
      acid substitution have been found. We investigated genetic variants in the
      promoter region of the ALOX5AP gene and the association with ischemic stroke in a
      north Chinese Han population. METHODS: 505 cases of ischemic stroke and 500 age-
      and gender-matched controls of the north Chinese Han population were enrolled.
      Genetic variants in the promoter region of the ALOX5AP gene were identified by
      polymerase chain reaction and DNA sequencing. 40 cases and 40 controls were
      randomly selected and compared for serum leukotriene B(4) (LTB(4)) concentration.
      The effect on ischemic stroke was evaluated by logistic regression. RESULTS:
      Three genetic variants were identified, including a mutation (-519 G > A), an
      insertion and deletion polymorphisms (-581_582 Ins A) and a single nuclear
      polymorphisms (-946 A > G). Association study showed that the II genotype of 
      581_582 Ins A was significantly associated with ischemic stroke of a large artery
      atherosclerosis (OR = 3.50, 95% CI = 1.93-6.36, p = 0.0002) and undetermined
      etiology (OR = 3.66, 95% CI = 1.92-6.94, p = 0.0006). No significant association
      was found between the -519 GA genotype (OR = 0.35, 95% CI = 0.02-5.88, p = 0.46),
      -946 AG genotype (OR = 1.35, 95% CI = 0.85-2.16, p = 0.21) and ischemic stroke.
      There was no significant difference in serum LTB(4) concentration between cases
      (n = 40) and controls (n = 40) (log serum LTB(4) of cases vs. controls: 2.67 +/-
      0.14 vs. 2.73 +/- 0.18 pg/ml, p = 0.10). However, the serum LTB(4) concentration
      was significantly higher in participants with the II genotype of -581_582 Ins A
      (n = 12) than that of participants with the DD genotype (n = 68) (log serum
      LTB(4) of participants with II genotype vs. DD genotype: 2.82 +/- 0.18 vs. 2.68
      +/- 0.15 pg/ml, p = 0.01). CONCLUSION: The -581_582 Ins A polymorphism might be a
      novel genetic risk factor for ischemic stroke in a north Chinese Han population.
      Further studies on molecular mechanism are warranted.

PMID- 21893979
TI  - Post-interventional microembolism: cortical border zone is a preferential site
      for ischemia.
AB  - BACKGROUND: Previous diffusion-weighted MRI (DWI) studies have indicated that 10
      40% of patients have silent embolism during neurointerventional procedures.
      However, lesion patterns of the embolisms have not been adequately investigated.
      METHODS: DWI was taken within 7 days before and 48 h after cerebral angioplasty
      and stent procedures. New lesions on the follow-up DWI were analyzed in the non
      treated arterial territories. Based on the arterial territories, supratentorial
      lesions were classified into cortical lesions and subcortical lesions. Cortical
      lesions were subdivided into cortical border zone and cortical proper lesions.
      Subcortical lesions were divided into deep perforator and internal border zone
      lesions. Infratentorial lesions were divided into brainstem and cerebellar
      lesions. RESULTS: 72 patients were included in this study. There were 223 new DWI
      lesions (1-23 lesions) in the non-treated arterial territories of 37 patients.
      There were 154 cortical lesions, 45 cerebellar lesions, 21 subcortical lesions
      and 3 brainstem lesions. Analysis of the distribution pattern of cortical lesions
      showed that 88 of 154 lesions were located at the cortical border zone. Of the
      subcortical lesions, 13 of 21 lesions were located at the internal border zone
      area, within the corona radiata and centrum ovale. Only 4 lesions were located at
      the deep perforator territory. Infratentorial lesions were mostly located at the
      cerebellar hemisphere (45/48). Most lesions were tiny infarcts (<5 mm diameter);
      7 of 223 lesions were >10 mm in diameter. CONCLUSIONS: Interventional-angiography
      related microembolisms mostly lodge in the cerebral cortical border zone area and
      cerebellar hemisphere. Microembolisms to the deep perforating artery territory
      are distinctly rare.

PMID- 21893980
TI  - Paroxysmal atrial fibrillation is more prevalent than persistent atrial
      fibrillation in acute stroke and transient ischemic attack patients.
AB  - BACKGROUND: Atrial fibrillation (AF) is a common cause of ischemic stroke and
      transient ischemic attack (TIA). More extensive diagnostic effort is required to
      detect paroxysmal AF (pxAF) than persistent AF (pAF); the prevalence of pxAF in
      stroke patients is unknown. We evaluated the prevalence of pAF and pxAF in
      ischemic stroke and TIA patients. METHODS: Consecutive patients with acute
      ischemic stroke/TIA were enrolled prospectively. We aimed to detect patients with
      a history of AF, with AF newly diagnosed in the emergency room (ER), or with
      newly diagnosed AF during a 3-month period following the event. Differences in
      the frequency of AF diagnosis with respect to the disposition of patients after
      ER work-up were assessed. RESULTS: A total of 692 patients were enrolled (male:
      52.2%; ischemic stroke: 69.1%; TIA: 30.9%). A previously documented history of AF
      was present in 19.7% (pAF: 47.1%, pxAF: 52.9%). In 3.8% of patients, AF was newly
      diagnosed in the ER (pxAF: 61.5%) and in 5.2% during the 3-month follow-up
      period. The overall prevalence of AF was 28.6% (pxAF: 62.6%). Previously
      documented pxAF evaded diagnosis at ER presentation in 48.6%. The prevalence of
      AF increased with age (p < 0.001). Patients with pxAF were younger than those
      with pAF (p = 0.004) and more often female (p = 0.05). The presence of any AF was
      associated with higher initial NIHSS scores (p < 0.001) and higher modified
      Rankin scores after 3 months (p < 0.001). CONCLUSION: pxAF occurs more often than
      pAF in stroke/TIA patients. As effective stroke prevention is available for AF,
      it is important to develop and evaluate sensitive methods for detecting pxAF.

PMID- 21893981
TI  - Recurrent stroke after lobar and deep intracerebral hemorrhage: a hospital-based
      cohort study.
AB  - BACKGROUND: Recurrent stroke rates after intracerebral hemorrhage (ICH) vary
      widely between observational studies due to differences in ICH etiology and risk
      for thromboembolic events. We therefore aimed to assess the patient
      characteristics and prognosis after deep and lobar ICH in a well-characterized,
      multicenter, hospital-based cohort. METHODS: Patients were prospectively
      documented in 13 German neurological stroke centers. Of 744 patients with
      spontaneous ICH discharged alive, 516 (69.4%) gave informed consent and 496
      (66.7%) could be followed up by central telephone interview over a mean duration
      of 2 years. RESULTS: In patients with deep ICH, the Kaplan-Meier estimate for
      stroke during the first year was 5.8% (95% CI 2.9-8.7) and the overall annual
      rate (calculated over a 3-year period) was 2.9% (95% CI 1.6-4.1). In patients
      with lobar ICH, the Kaplan-Meier estimate for stroke during the first year was
      7.8% (95% CI 3.1-12.5) and the overall annual rate was 7.2% (95% CI 3.8-10.6). At
      the last follow-up before recurrent stroke or end of study, 141 patients (28.4%)
      overall received antiplatelet agents, and 12 (2.4%) received oral
      anticoagulation. No difference could be found for recurrent ICH under
      antiplatelet agents versus no antithrombotic medication. CONCLUSION: The risk of
      recurrent stroke after lobar ICH remains high beyond the first year, whereas it
      decreases after 1 year in patients with deep ICH. Antiplatelets are prescribed in
      a considerable number of patients even though the risk-benefit ratio after ICH
      remains unknown.

PMID- 21893982
TI  - Interaction studies of an anticancer alkaloid, (+)-(13aS)-deoxytylophorinine,
      with calf thymus DNA and four repeated double-helical DNAs.
AB  - BACKGROUND: Phenanthroindolizidine alkaloids are a family of plant-derived
      compounds with significant antineoplastic activity. The specific biomolecular
      targets of these alkaloids have not yet been clearly identified. (+)-(13aS)
      deoxytylophorinine is a new phenanthroindolizidine alkaloid originally extracted
      from the roots of Tylophora atrofolliculata and Tylophora ovata in our institute.
      (+)-(13aS)-deoxytylophorinine exerts both in vitro and in vivoanticancer
      activities. METHODS: The in vivo anticancer effects and toxicity of this compound
      were investigated in mice, and interactions between this compound and double
      helical DNA sequences were studied in detail with circular dichroic spectroscopy
      and fluorescence spectroscopy. Viscosity measurements were applied to check the
      interactive mode between this compound and DNA. RESULTS: Potent anticancer
      effects were observed in vivo. Also, concentration-dependent interactions were
      observed and this compound seemed to interact in a sequence-specific manner with
      AT-repeated sequences of double-helical DNA. Such interactions were proved to be
      intercalating by viscosity measurements. CONCLUSIONS: Anticancer alkaloid (+)
      (13aS)-deoxytylophorinine can have sequence-specific interactions with DNA in an
      intercalating manner.

PMID- 21893983
TI  - Celecoxib, a selective cyclooxygenase-2 inhibitor, attenuates renal injury in a
      rat model of Cisplatin-induced nephrotoxicity.
AB  - BACKGROUND: Cisplatin is an effective chemotherapeutic agent successfully used in
      the treatment of a wide range of tumors. Nevertheless, nephrotoxicity has
      restricted its clinical use. Recent studies have strongly suggested that
      inflammatory mechanisms may play an important role in the pathogenesis of
      cisplatin nephrotoxicity. Celecoxib, a selective cyclooxygenase-2 inhibitor used
      as anti-inflammatory, may therefore have a protective effect on cisplatin-induced
      renal injury. METHODS: In the present study, rats were injected intraperitoneally
      with a single dose of cisplatin (7 mg/kg) and/or celecoxib (30 mg/kg) for 5 days.
      RESULTS: Nephrotoxicity manifested biochemically by elevations in serum
      creatinine, blood urea nitrogen, and proteinuria, and an increase in kidney
      weight as a percentage of total body weight. In addition, a marked decrease in
      serum albumin was observed. Lipid peroxidation in the kidney was monitored by
      measuring the malondialdehyde level and glutathione content, which were increased
      and depleted, respectively. Administration of celecoxib with cisplatin attenuated
      cisplatin-induced changes in kidney function parameters and oxidative stress
      markers. Histopathological examination of the kidney confirmed these results.
      CONCLUSION: In conclusion, this study indicates that celecoxib may be a promising
      drug for clinical use as a nephroprotectant against cisplatin-induced
      nephrotoxicity.

PMID- 21893984
TI  - Aminoguanidine, a selective nitric oxide synthase inhibitor, attenuates
      cyclophosphamide-induced renal damage by inhibiting protein nitration and
      poly(ADP-Ribose) polymerase activation.
AB  - BACKGROUND: Cyclophosphamide (CP) is an antineoplastic agent that is used for the
      treatment of many neoplastic diseases. Renal damage is one of the dose-limiting
      side effects of CP. Recent studies show that nitrosative stress plays an
      important role in CP-induced renal damage. AIM: The purpose of our study was to
      investigate whether aminoguanidine (AG), a selective inducible nitric oxide
      synthase inhibitor, protects against CP-induced nitrosative stress and renal
      damage. METHOD: Renal damage was induced in rats by administration of a single
      injection of CP at a dose of 150 mg/kg body weight intraperitoneally. For the AG
      pretreatment studies, the rats were injected intraperitoneally with AG at a dose
      of 200 mg/kg body weight 1 h before administration of CP. The control rats
      received AG or saline alone. All the rats were killed 16 h after the
      administration of CP or saline. Pretreatment with AG prevented CP-induced
      nitration of protein tyrosine and poly(ADP-ribose) polymerase (PARP) activation.
      RESULT: Pretreatment with AG attenuated CP-induced renal damage. The present
      study demonstrates that AG is effective in preventing CP-induced renal damage and
      also that the protective effect is from its ability to inhibit nitric oxide
      induced protein nitration and PARP activation. CONCLUSION: The present study
      shows that AG can prevent CP-induced renal damage by inhibiting protein tyrosine
      nitration and PARP activation. Thus, a more efficient and comfortable therapy can
      be achieved for patients in need of CP treatment. AG appears to be a promising
      drug for the prevention of nephrotoxicity of CP.

PMID- 21893985
TI  - Pharmacology of renal endothelin receptors.
AB  - Endothelin (ET)-1 is the major isoform in the human kidney where it interacts
      with two G protein-coupled receptors, ET(A) and ET(B). It contains high densities
      of ET receptors, but in contrast to most other peripheral organs, the majority
      (70%) are of the ET(B) subtype and largely have a differential distribution to
      ET(A) receptors within renal cells, thus mediating contrasting physiological and
      pathophysiological actions. ET-1 remains the most potent constrictor of human
      isolated vessels, including those of the kidney which are particularly sensitive
      to the actions of this peptide. The pharmacological response is unusual in being
      sustained for a considerable period of time and slow to wash out. Smooth muscle
      cells of the renal vasculature mainly express ET(A) receptors, and ET(A)
      selective antagonists fully block these constrictor responses. The vascular
      endothelium only expresses ET(B) receptors. ET-1 also acts in an autocrine or
      paracrine manner, and binds to ET(B) receptors to stimulate the release of
      vasodilators. ET-1 is unusual amongst the mammalian bioactive peptides in
      possessing two disulphide bridges, conferring resistance to enzymatic
      degradation. However, the plasma half-life of ET-1 is surprisingly short as a
      result of the second major function of endothelial ET(B) receptors in removing ET
      1 from the circulation, mainly in the kidneys and lungs. Thus, ET(B) receptors
      have a critical role in protecting target organs such as the heart and may limit
      the detrimental vasoconstrictor effect caused by upregulation of ET-1 associated
      with disease. Inhibition of the renal medullary ET(B) system causes sodium
      retention because of its role in systemic fluid and electrolyte homeostasis.
      ET(A)/ET(B) antagonists would be expected to block the beneficial vasodilatory,
      clearing, and natriuretic actions of ET(B) receptors. Since many of the
      deleterious actions of ET-1, vasoconstriction, mesangial cell proliferation, and
      inflammation occur mainly via ET(A) receptors, selective ET(A) blockade may be
      more beneficial in renal disease.

PMID- 21893986
TI  - Renal function and blood pressure: molecular insights into the biology of
      endothelin-1.
AB  - The therapeutic implications of the actions of endothelin (ET)-1 upon renal and
      cardiovascular function are evident. Among other diseases, ET-1 is recognized to
      be involved in hypertension and renal failure and, in a rush to develop novel
      treatments, has been extensively studied. However, given the broad localization
      of the two receptors (ET(A) and ET(B)) and the diverse effects resulting from
      their activation, analysis of the role of ET-1 in kidney-regulated blood pressure
      remains complicated. Moreover, the actions of ET-1 depend upon the cell type and
      physiological situation. To add to the complexity, both receptors often activate
      opposing signaling pathways within a single cell. Thus, until recently, reliable
      insights into the respective involvement of both receptors in the physiology and
      pathology of the kidney were eagerly awaited. These have been obtained using mice
      that are genetically modified for different members of the ET system. In this
      article, the molecular biology of ET-1 and its receptors in the control of renal
      vasculature tonicity, glomerular function, and management of water and salt
      reabsorption is discussed. The role of renal ET-1 in the context of blood
      pressure regulation will be discussed, and the potential of utilizing ET receptor
      antagonism in the treatment and prevention of glomerular and proteinuric diseases
      is also outlined.

PMID- 21893987
TI  - Endothelin and the renal vasculature.
AB  - The endothelin (ET) system comprises a family of three isopeptides (ET-1, ET-2,
      and ET-3)involved in diverse physiological and pathophysiological events. ET-1 is
      the major renal peptide that exerts its biological activity by binding to ET(A)
      and ET(B) receptors. Both ET(A) and ET(B) receptors are expressed by renal
      microvascular smooth muscle cells, where activation causes vasoconstriction.
      ET(B) receptors are also expressed by microvascular endothelial cells, where
      activation leads to vasodilator responses. ET-1 influences preglomerular and
      postglomerular microvascular tone and thus can significantly influence renal
      hemodynamics. Alteration of renal ET-1 synthesis and receptor expression has been
      reported in cardiovascular diseases, and could contribute to renal injury by
      altering renal microvascular reactivity. In this brief review, we will try to
      summarize what is known about ET control of renal microvascular function.

PMID- 21893988
TI  - Endothelin signaling and actions in the renal mesangium.
AB  - Endothelins (ETs), and particularly ET-1, activate a complex network of
      interconnected signaling cascades in mesangial glomerular cells, which play an
      important role in the physiology and pathophysiology of the glomerulus. Excessive
      stimulation of ET-1 production by mesangial cells results in activation of a wide
      variety of signaling pathways in the renal mesangium, which is at least partially
      responsible for glomerular damage in the setting of diabetes, hypertension, and
      glomerulonephritis. Mesangial cells express both types of ET receptors (ET(A)-R
      and ET(B)-R), which are G protein-coupled receptors. ET-1 induces mobilization of
      Ca(2+); activation of phospholipases A, C, and D; activation of protein kinase C;
      GTP-loading of several families of small GTPases; and activation of intracellular
      tyrosine kinases resulting in protein tyrosine phosphorylation of adaptor,
      scaffolding, and signaling proteins. ET-1-triggered posttranslational
      modification of signaling molecules sets the base for the formation of multiunit
      signaling complexes which define the specificity of ET signaling. Long-term
      effects of ET-1 are also mediated via increased expression of particular
      signaling proteins. It is likely that ET-1 acts via ET(A)-R to trigger the
      contraction of mesangial cells, which decreases glomerular filtration area and
      reduces the glomerular filtration rate, promoting impaired renal function.
      Proliferation of mesangial cells is observed in the progress of several types of
      glomerulonephritis. ET-1 is a potent mitogen of mesangial cells and the ability
      of ET-1 to support mesangial cell proliferation is likely to be associated with
      both recruitment of cytoplasmic tyrosine kinases which activate the Shc-Sos-Ras
      Raf-MEK-ERK signaling pathway and transactivation of the EGF receptor. The
      guanine nucleotide exchange factor betaPix and the adaptor protein p66(Shc) are
      important players in Akt-independent inactivation of FOXO3a transcription factor.
      This results in the depletion of the inhibitor of cell cycle progression
      p27(kip1), and promotion of mesangial cell proliferation. Plentiful evidence
      suggests an essential role of ET-1-signaling and action in the renal mesangium
      for renal biology and pathobiology.

PMID- 21893990
TI  - Role of endothelin in thick ascending limb sodium chloride transport.
AB  - The thick ascending limb of the loop of Henle reabsorbs 20-30% of filtered sodium
      chloride (NaCl) and generates the osmotic gradient necessary for water absorption
      in the distal nephron. It is second only to the collecting duct as a source of
      renal endothelin (ET)-1, which inhibits NaCl reabsorption in the thick ascending
      limb by reducing NaCl entry into the cell via the furosemide-sensitive
      Na(+)/K(+)/2 Cl(-) cotransporter. The mechanism by which this occurs appears to
      be due to activation of ET(B) receptors, phosphatidylinositol 3 kinase and Akt,
      and enhanced nitric oxide production by nitric oxide synthase 3. ET-1 may inhibit
      thick ascending limb NaCl absorption in either an autocrine or paracrine fashion.
      High-salt intake elevates ET-1 release by thick ascending limbs, although the
      molecular mechanism involved is unknown. Enhanced ET-1 release and inhibition of
      thick ascending limb NaCl absorption are thought to be among the mechanisms
      required to eliminate a salt load without increasing blood pressure. However, we
      still have much to learn about how ET-1 inhibits thick ascending limb NaCl
      absorption, how release and processing of ET-1 are regulated, and the receptors
      involved.

PMID- 21893991
TI  - Endothelins and kidney acidification.
AB  - Endothelins (ETs) were initially identified for their vasoactive properties, but
      they also influence kidney tubule transport including acidification. They
      contribute importantly to enhancing kidney acidification in response to an acid
      challenge to systemic acid-base balance and enhance tubule acidification in
      settings of chronically reduced glomerular filtration rate (GFR) as in chronic
      kidney disease. ETs also contribute pathophysiologically to the increased kidney
      acidification in some forms of chronic metabolic alkalosis. In addition,
      chronically increased ET activity in the kidney, as in chronic kidney disease
      with reduced GFR, might also mediate the progressive GFR decline observed in some
      nephropathies. These exciting insights have led to the need for continued
      investigation regarding the physiologic contribution of ETs to kidney
      acidification and the possible pathophysiologic consequences of the associated
      increased kidney ET activity.

PMID- 21893989
TI  - Regulation of sodium transport in the proximal tubule by endothelin.
AB  - Human essential hypertension and rodent genetic hypertension are associated with
      increased sodium transport in the renal proximal tubule and medullary thick
      ascending limb of Henle. The proximal tubule, which secretes endothelin (ET),
      expresses the ET(B) receptor. Low (nM) concentrations of ET, via the ET(B)
      receptor, inhibit sodium and water transport and ATP-driven drug secretion in the
      proximal tubule. In contrast, very low (pM) and high nM concentrations of ET
      increase renal proximal sodium transport, but the receptor involved remains to be
      determined. The natriuretic effect of ET(B) receptor stimulation is impaired in
      spontaneously hypertensive rats, due in part to a defective interaction with D(3)
      dopamine and angiotensin II type 1 receptors. Impaired ET(B) receptor function in
      the renal proximal tubule may be important in the pathogenesis of genetic
      hypertension.

PMID- 21893992
TI  - Endothelin and collecting duct sodium and water transport.
AB  - The renal collecting duct (CD) produces and binds more endothelin (ET)-1 than any
      other region of the kidney. ET-1 has the potential to act as an autocrine
      regulator of CD function since ET-1 is secreted abluminally and ET receptors are
      located primarily on the basolateral side of the CD cell. A large number of in
      vitro studies have supported this notion of an autocrine function for ET-1,
      demonstrating that the peptide, largely through activation of the ET(B) receptor,
      inhibits both sodium (Na) and water reabsorption in the CD. The physiologic
      relevance of these findings has been confirmed in vivo wherein mice with CD
      specific knockout of ET-1 are hypertensive on a normal Na diet and develop
      worsened hypertension associated with Na retention when placed on a high-Na diet.
      Similarly, CDET-1-deficient mice demonstrate enhanced responsiveness to
      vasopressin and an impaired ability to excrete an acute water load. CD-specific
      knockout of both ET(A) and ET(B) receptors together causes a similar hypertensive
      and Na-retaining phenotype. The mechanisms by which ET-1 exerts its effects on CD
      Na and water reabsorption are being increasingly understood. ET-1 inhibits
      epithelial Na channel (ENaC) activity through src- and mitogen-activated protein
      kinase-dependent pathways; channel number is also reduced by a beta1Pix-dependent
      mechanism. In addition, nitric oxide is an important modulator of ET-1 actions on
      the ENaC, although the mechanism by which this occurs remains to be determined.
      ET-1 reduces CD water reabsorption by inhibition of vasopressin-stimulated
      adenylyl cyclase activity through G(i) and protein kinase C-dependent pathways,
      leading to a reduction in cellular cAMP levels. Taken together, these findings
      indicate that the CD ET system is an important physiologic regulator of systemic
      blood pressure and volume homeostasis.

PMID- 21893993
TI  - Endothelin in the control of renal sympathetic nerve activity.
AB  - The kidney is densely innervated by sympathetic nerves. Increases in renal
      sympathetic nerve activity (RSNA) decrease urinary sodium excretion. The kidney
      also has abundant afferent sensory innervation, located primarily in the renal
      pelvic wall. Sympathetic nerve fibers and afferent nerve fibers often run
      separately but intertwined in the same nerve bundles in the renal pelvic wall,
      providing anatomic support for a functional interaction between RSNA and afferent
      renal nerve activity (ARNA). Activation of RSNA increases ARNA, which in turn
      decreases RSNA by activation of the renorenal reflexes. Thus, RSNA-induced
      increases in ARNA exert a powerful negative feedback control of RSNA via
      activation of the renorenal reflexes in the overall goal of maintaining low RSNA
      to facilitate urinary sodium excretion. A high-sodium diet enhances and a low
      sodium diet reduces the RSNA-induced increases in ARNA. The physiologic
      importance of the dietary-induced changes in the RSNA-mediated increases in ARNA
      is underlined by salt-sensitive hypertension in rats lacking afferent renal
      innervation. Endothelin (ET), ET(A) receptors (R), and ET(B)-R are present in the
      renal pelvic wall. ET plays a modulatory role in the activation of the afferent
      renal nerves that is dependent on dietary sodium intake. In a high-sodium diet,
      increased activation of ET(B)-R facilitates the interaction between RSNA and ARNA
      resulting in suppression of RSNA, via activation of the renorenal reflexes, to
      limit sodium retention. In a low-sodium diet, increased activation of renal
      pelvic ET(A)-R suppresses the interaction between RSNA and ARNA which increases
      RSNA via impairment of the renorenal reflex mechanism, eventually leading to
      sodium retention. These findings suggest that the increased renal sympathetic
      nerve activity and salt-sensitive hypertension in ET-1/ET(B)-R-deficient subjects
      is, at least in part, related to suppressed interaction between RSNA and ARNA.

PMID- 21893994
TI  - Endothelin and podocyte injury in chronic kidney disease.
AB  - The identification of patients at increased risk for chronic kidney disease
      offers the potential to prevent or delay end-stage renal disease and the
      associated cardiovascular events. Data from recently completed controlled
      clinical trials of endothelin (ET) receptor blockers confirmed their potent
      antiproteinuric effect after a number of preclinical studies. A spectrum of
      proteinuric glomerular diseases results from podocyte abnormalities and, in
      return, impact podocyte structure and function. Because podocytes are cells in
      the glomerulus that form a crucial component of the glomerular filtration
      barrier, contributing to size selectivity and maintaining a large filtration
      surface, we focus on evidence that suggest ET-1 may promote podocyte injury
      thereby aggravating albumin urinary loss and alteration of the glomerular
      microvasculature. Systematic confrontation of animal models and studies in human
      subjects should help decipher pathophysiological mechanisms whereby the local
      renal ET system promotes podocyte injury and chronic kidney disease in specific
      pathophysiological contexts. Current evidence suggests that more experimental and
      clinical attention should be paid to conditions with increased vascular or
      endocapillary ET-1 production on the one hand, and in diseases with altered
      podocyte phenotype and survival such as focal segmental glomerulosclerosis and
      crescentic glomerulonephritis on the other. These conclusions may assist
      clinicians in creating optimal clinical trials for patients at increased risk for
      or with overt chronic kidney disease.

PMID- 21893995
TI  - Endothelin in diabetic renal disease.
AB  - Today diabetic nephropathy is the leading course of end-stage renal disease; the
      incidence and prevalence of diabetic renal disease is still continuing to
      increase, particularly in the Western world. Despite improvements in diagnosis
      and treatment of diabetic nephropathy, only partial renal protection is reached
      with the current standard therapy regiments, including angiotensin-converting
      enzyme inhibitors and/or angiotensin receptor blockers. Against this background,
      it is of particular importance to learn more about the pathogenesis of diabetic
      nephropathy and to find new therapeutic approaches which alone or in combination
      with standard therapy have the potential to prevent or delay the progression of
      diabetic nephropathy, thus improving kidney and patient survival. Among others,
      endothelin (ET) receptor blockers have emerged as a potential therapeutic option
      that operates on the basis of physiological and pathophysiological effects of
      endothelin. Of note, the ET system was shown to be involved in hypertension and
      kidney disease, particularly proteinuric nephropathies, and there is good
      experimental data indicating a specific role of ET in the pathogenesis and
      progression of diabetic nephropathy. ET receptor blockers have been shown to be
      nephroprotective in animal models of type 1 and type 2 diabetes mellitus with the
      effects partly independent of blood pressure lowering. In patients with
      hypertension and diabetic nephropathies, the data is controversial and depends on
      the stage of the disease and the drug used. It was only recently that a large
      international clinical study (ASCEND) provided evidence for beneficial effects of
      ET antagonist treatment, i.e. reduction in proteinuria. Due to the premature
      termination of the study, however, hard endpoints like death could no longer be
      assessed. Another very recent randomized, double-blind, placebo-controlled trial
      of subjects with diabetic nephropathy also provided evidence for a specific
      antiproteinuric effect of the ET receptor antagonist atrasentan on top of an
      already existing blockade of the renin-angiotensin system. Thus, it appears
      currently of great scientific and clinical interest to shed some light on the
      role of the ET system and its blockade in diabetic nephropathy.

PMID- 21893996
TI  - Endothelin, nitric oxide, and reactive oxygen species in diabetic kidney disease.
AB  - The mechanism(s) of the endothelin (ET) and reactive oxygen species pathways in
      conjunction with the nitric oxide (NO) pathway that promote and/or blunt the
      progression of diabetic kidney disease have been the focus of many laboratories'
      efforts to reveal new therapeutic targets. In both animal models and patients
      with diabetic nephropathy, pharmacological blockade of ET receptors results in a
      significant reduction. However, edema has been documented as a persistent side
      effect. It is unclear whether selective ET(A) antagonists or nonselective ET(A/B)
      antagonists are preferred in diabetic conditions. We have proposed that ET(B)
      activates the NO pathway to blunt diabetes-induced nephropathy such that ET(A)
      selectivity should be more efficacious. The NO pathway in diabetes facilitates
      vascular dysfunction while in the renal tubular system, NO serves to blunt
      disease progression. NO synthase isoform activity is also critically regulated in
      diabetic kidney disease within the renal vascular and tubular systems through a
      complex interaction with reactive oxygen species. We will examine the
      complexities of the ET and NO pathways in diabetic kidney disease to propose
      novel mechanisms for future investigation.

PMID- 21893997
TI  - Endothelin in renal inflammation and hypertension.
AB  - Over the years, a very large amount of evidence has accumulated indicating that
      endothelin (ET)-1 is an important stimulus for inflammation. This is true for a
      wide range of organ system diseases, including chronic kidney disease.
      Nonetheless, our understanding of the role and mechanisms by which ET-1 promotes
      the activation of both the innate and adaptive immune systems is not understood.
      ET-1 can directly activate neutrophils as well as endothelial cells to stimulate
      production of chemoattractant factors, such as monocyte chemoattractant factor-1,
      and increase synthesis of cell adhesion molecules, such as soluble ICAM-1. The
      mechanisms that trigger these events, however, are less clear. Elevated blood
      pressure as well as hyperglycemia could be important factors that facilitate ET-1
      dependent inflammation. While renal inflammation has not been used as an endpoint
      for drug development, the rationale for the use of ET antagonists as anti
      inflammatory agents in chronic kidney disease is quite strong, based on animal
      studies and at least one study in humans with nondiabetic nephritis. While the
      preponderance of evidence suggests that ET(A) selective antagonists are
      advantageous over combined ET(A/B) receptor blockers, considerably more work
      needs to be done in order to understand the complex role of ET in renal
      inflammation.

PMID- 21893998
TI  - Endothelin in chronic proteinuric kidney disease.
AB  - The incidence of chronic kidney diseases is increasing worldwide at an alarming
      rate. As this is emerging as a global threat to human health, present efforts are
      concentrated on the identification of new treatments that slow or even reverse
      the progression of chronic nephropathies. Endothelin (ET)-1 is a potent
      vasoconstrictor peptide with proinflammatory, mitogenic, and profibrotic effects,
      and it contributes to both normal renal physiology and pathology. There is robust
      experimental and clinical evidence for the role of ET-1and its cognate receptors
      in many progressive renal disorders. The effectiveness of ET receptor antagonists
      in improving renal hemodynamics and reducing fibrosis has been largely documented
      in experimental animals. However, whether selective ET(A) or dual ET(A)/ET(B)
      receptor antagonists are preferable is still a matter of debate. Combined
      therapies, including ET receptor antagonists, are promising to maximize partial
      renoprotection achieved with blockade of the renin-angiotensin system,
      particularly when treatment is given in the latter phase of the disease. The
      focus of this review is to explore the role of ET-1 in kidney diseases and to
      shed light on the novel pharmacological setting in chronic nephropathies.

PMID- 21893999
TI  - Endothelin in renal injury due to sickle cell disease.
AB  - Sickle cell disease (SCD), the first 'molecular disease' to be identified, has
      been well characterized as a single amino acid molecular disorder of hemoglobin
      leading to its pathological polymerization, with resulting red cell rigidity that
      causes poor microvascular blood flow, with consequent tissue ischemia and
      infarction. Thus, the manifestations of SCD chronic renal disease have long been
      considered clinical manifestations of an obstructive vasculopathy of the arterial
      and capillary microcirculation. Recently, accumulating evidence have indicated
      that blood vessel functions are affected by SCD, involving abnormal vascular tone
      and activated endothelium. These abnormalities are particularly prominent in the
      kidney where specific biochemical conditions in the medulla and papilla favor
      change in endothelial phenotype and in tubular phenotype that, in turn, may
      promote dysfunction and destruction of this organ through active endothelin (ET)
      1 production and signals. High ET-1 urinary output in SCD subjects at steady
      state may reflect increased tubular activation of ET-1 production acting on the
      collecting duct thereby favoring the constant hyposthenuria. Chronically,
      augmented ET-1 concentrations in the SCD kidney would further aggravate ischemia
      and sickling through actions on vasa recta and red blood cells. The kidneys
      suffer multiple ischemic hits during SCD as consequences of vasos-occlusive
      crisis (VOC). Blockade of ET receptors unraveled the major vasoconstrictive role
      of ET-1 in the pathophysiology of VOC, stressing the pivotal role of abnormal
      endothelial phenotype in this hemoglobinopathy and opening potential new
      therapeutic options. At last, indirect evidence suggest that ET-1 may be involved
      in the progression of chronic glomerulosclerosis affecting a number of patients.
      In fact, sickle cell nephropathy is an emerging severe disease that requires
      pathophysiological studies and development of specific therapies.

PMID- 21894000
TI  - Endothelin in polycystic kidney disease.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic
      kidney disease in man and is caused by germline mutations in PKD1 or PKD2.
      Affected patients develop progressively enlarged kidneys due to the growth of
      multiple renal epithelial cysts. Several studies have demonstrated marked
      intrafamilial phenotypic variability in PKD1 or PKD2 pedigrees, indicating the
      importance of nonallelic factors such as genetic modifying loci in determining
      individual phenotype. Endothelin (ET)-1 exerts multiple and often opposing
      effects on different aspects of renal physiology through its major ET receptor
      subtypes, ET(A) and ET(B). Recent studies have reported that EDN1 and EDNRA
      polymorphisms can influence the age of onset of end-stage renal disease in ADPKD.
      Both circulating and local ET-1 systems are abnormally activated in human disease
      and experimental models, and ET(A) receptor expression is specifically
      upregulated in human ADPKD kidneys. Overexpression of ET-1 in transgenic mice is
      sufficient to trigger cyst initiation. However, studies utilizing selective ET(A)
      and ET(B) receptor antagonists to delay cystic disease progression in rodent PKD
      models have proved disappointing and do not support further extension into
      clinical trials. A critical balance between ET(A) and ET(B) action in the cystic
      kidney appears to be necessary to maintain kidney structure and function. Current
      evidence suggests that ET-1 and its receptors act as major modifying genes for
      renal disease progression in ADPKD. The future challenge will be to translate
      these findings to modify disease severity or for predicting prognosis in man.

PMID- 21894001
TI  - Endothelin antagonism and reversal of proteinuric renal disease in humans.
AB  - Endothelin (ET)-1 is a powerful mitogen and vasoconstrictor that contributes to
      cardiovascular and renal pathologies. In the kidney, ET causes vasoconstriction,
      sodium retention, mesangial cell inflammation and proliferation, hypertrophy of
      glomerular capillaries, and podocyte injury. The latter, due to destruction of
      the glomerular filtration barrier, is a key factor for renal protein loss.
      Experimental and recent clinical studies suggest that orally active drugs
      inhibiting ET(A) receptors are capable of not only inhibiting the progression,
      but also reversing glomerulosclerosis-related renal injury. Clinical studies
      using ET receptor antagonists (ERAs) have found regression of proteinuria which
      serves as a functional indicator of glomerular filtration barrier injury. The
      effects of ERA therapy can be observed in the presence of inhibition of the renin
      angiotensin system, suggesting arenin-angiotensin system-independent therapeutic
      effect of ERAs. Thus, ET blockade is not an 'add-on' treatment, but represents an
      independent therapeutic principle. This article will discuss the underlying
      mechanisms of the antiproteinuric effects of ET antagonists, and summarize recent
      clinical trials in the field and the therapeutic potential of the ERA class of
      drugs for renal medicine.

PMID- 21894002
TI  - Endothelin antagonism in patients with resistant hypertension and hypertension
      nephropathy.
AB  - Resistant hypertension is a failure to achieve a blood pressure (BP) goal of <
      140/90 mm Hg despite treatment with at least three different antihypertensive
      medications classes at a maximally tolerated dose and including a diuretic. The
      most important systems that require alteration include the renin-angiotensin
      aldosterone system, sympathetic nervous system, and (more recently) the
      endothelin (ET) system. To date, several clinical trials have assessed the
      effects of ET antagonism, both selective and nonselective, on BP control in
      humans. The nonselective ET antagonist bosentan was evaluated in patients with
      mild-to-moderate hypertension. Bosentan was able to lower diastolic BP when
      compared to placebo and, similarly, to enalapril. Similar findings have been
      published for darusentan, an ET receptor antagonist with higher affinity for the
      type A receptor. More recent research has focused on the impact of ET in the
      setting of resistant hypertension. Studies with darusentan as an add-on therapy
      in patients with resistant hypertension found a significant BP-lowering effect of
      17/10 mm Hg compared to placebo. This BP-lowering effect was similar at higher
      doses. In a similar patient cohort, darusentan also lowered mean 24-hour BP to a
      greater extent than the central alpha2-agonist guanfacine. Another selective
      ET(A) antagonist, atrasentan, provided other benefits on metabolism in addition
      to its antihypertensive effect. Atrasentan significantly decreased glucose in
      diabetes and improved lipid profiles while slowing coronary artery disease
      progression. Selective ET receptor blockade also has dose-dependent side effects.
      In a large number of trials, almost one third of the patients suffered excessive
      fluid retention and edema that was significantly higher than in the placebo
      groups. One trial, ASCEND, was terminated early due to an increased incidence of
      fluid retention and increased episodes of heart failure. Thus, this class of
      agents is effective in resistant hypertension, but lower doses with fewer side
      effects need to be developed.

PMID- 21894003
TI  - Endothelin receptor blockade in patients with diabetic nephropathy.
AB  - Diabetic nephropathy constitutes a major health care challenge. In the current
      review we summarize the rationale and preclinical data that suggest involvement
      of the endothelin (ET) system in the pathogenesis of this complication of
      diabetes. Early clinical studies suggest that blockade of the ET system indeed
      may have renoprotective effects, as reflected by a strong reduction in albumin
      excretion. A major challenge in the clinical development of ET receptor blockades
      for this indication will be to tease out the protective effects from potential
      off-target effects. Of particular concern is the edema formation during ET
      receptor blockade.

PMID- 21894004
TI  - Endothelin antagonism in patients with nondiabetic chronic kidney disease.
AB  - The incidence of chronic kidney disease (CKD) is increasing worldwide.
      Cardiovascular disease is strongly associated with CKD and constitutes one of its
      major causes of morbidity and mortality. Although current treatments for CKD
      focus on blood pressure and proteinuria reduction, many CKD patients have ongoing
      hypertension and residual proteinuria. Newer treatments are needed that not only
      act on these parameters, but also slow the progression of CKD and improve the
      cardiovascular risk profile of CKD patients. The endothelins (ETs) are a family
      of related peptides of which ET-1 is the most powerful endogenous vasoconstrictor
      and the predominant isoform in the cardiovascular and renal systems. The ET
      system has been widely implicated in both cardiovascular disease and CKD. ET-1
      contributes to the pathogenesis and maintenance of hypertension and arterial
      stiffness, as well endothelial dysfunction and atherosclerosis. By reversal of
      these effects, ET antagonists may reduce cardiovascular risk. In CKD patients,
      antagonism of the ET system may be of benefit in improving renal hemodynamics and
      reducing proteinuria. ET is likely also involved in the progression of renal
      disease, and data are emerging that suggest a synergistic role for ET receptor
      antagonists with angiotensin-converting enzyme inhibitors in slowing CKD
      progression.

PMID- 21894005
TI  - Endothelin antagonists in clinical trials: lessons learned.
AB  - Over the past 20 years, a large number of endothelin receptor antagonists (ERAs)
      have been developed, many of which underwent clinical testing. Yet, today only
      two ERAs are approved for the treatment of only two clinical indications, namely
      pulmonary arterial hypertension and scleroderma-related digital ulcers. Clinical
      development of ERAs has been hampered by problems with dosing, with the makeup of
      study cohorts, and adverse events. More recently, a number of studies evaluated
      the potential of ERA treatment for proteinuric renal disease. Although several
      ERAs were found to reduce proteinuria in patients with nephropathy, clinical
      testing was stopped for all but one drug. The reasons for the failure of some of
      these studies and general considerations about how to move forward with clinical
      studies involving ERAs in renal disease are discussed in this chapter.

PMID- 21894006
TI  - Remineralization potential of nano-hydroxyapatite on initial enamel lesions: an
      in vitro study.
AB  - The application of nano-hydroxyapatite (HA) in the repair of early caries lesion
      has received considerable attention. Neither the effects of the size of HA nor
      the effects of the effective pH range of nano-HA on remineralization have been
      investigated comprehensively, and the protective mechanism is still open for
      debate. To address these factors, the remineralization effect of nano-HA on
      demineralized bovine enamel is investigated under pH cycling conditions through
      surface and cross-sectional microhardness (CSMH) tests and polarized light
      microscopy (PLM). The percentage of surface microhardness recovery and integrated
      mineral loss obtained from CSMH tests demonstrated that nano-HA provides better
      remineralization than micro-HA. However, detailed investigation using CSMH tests
      and PLM indicated that nano-HA helped mineral deposition predominantly in the
      outer layer of the lesion and only had a limited capacity to reduce lesion depth.
      Nevertheless, the remineralization effect of nano-HA increased significantly when
      the pH was less than 7.0. Clearly, nano-HA has potential as an effective repair
      material and anticaries agent. Our findings also suggest that both the particle-
      and ion-mediated remineralization pathways in nano-HA may contribute to the
      repair of demineralized enamel.

PMID- 21894007
TI  - Modulation of liver fibrosis by adipokines.
AB  - Hepatic fibrosis is an integrated process triggered by chronic liver damage,
      leading to the accumulation of extracellular matrix. In patients with chronic
      liver disease, this process is favored by the presence of obesity or overweight,
      which are also relevant risk factors for the progression of nonalcoholic
      steatohepatitis. In this paper, we review the available evidence indicating the
      modulation of the fibrogenic process by adipokines, a group of cytokines secreted
      primarily by adipose tissue. In particular, we discuss in detail the role of
      leptin and adiponectin, which favor and limit the fibrogenic process,
      respectively. The possible involvement of other recently identified adipokines is
      also briefly outlined.

PMID- 21894008
TI  - Obesity and fatty liver are 'grease' for the machinery of hepatic fibrosis.
AB  - Nonalcoholic fatty liver disease (NAFLD) starts with hepatic steatosis, which can
      progress with inflammation to nonalcoholic steatohepatitis, and a subset of
      patients develop progressive fibrosis and ultimately cirrhosis. In the majority
      of cases, NAFLD is associated with (components of) the metabolic syndrome.
      Obesity, diabetes and hepatic steatosis are also independent risk factors for
      hepatic fibrosis in different chronic liver diseases. However, the question is
      whether it is actually nonalcoholic steatohepatitis and not 'simple' steatosis
      that promotes fibrosis progression based on hepatocellular injury. In this
      review, the concept will be put forward that (1) hepatic steatosis per se is
      profibrogenic, and (2) that in NAFLD development and progression of hepatic
      fibrosis is not simply determined by (the degree of) hepatic inflammation. In
      addition to the liver, this view is expanded to other organs affected by the
      metabolic syndrome, which affects hepatic injury and fibrosis also via
      extrahepatic pathophysiological alterations. In conclusion, fatty liver and the
      metabolic syndrome, respectively, have to be recognized as significant lubricants
      of hepatic fibrosis, and simple hepatic steatosis cannot be considered as benign.

PMID- 21894009
TI  - Mechanisms balancing tolerance and immunity in the liver.
AB  - The liver has a pivotal role in glucose, lipid and protein metabolism as well as
      in removal of toxins and waste products. A unique microanatomy and a network of
      resident scavenger cell populations specialized in endocytic uptake of antigens
      and macromolecules cooperatively mediate these salient hepatic functions together
      with parenchymal hepatocytes. Antigens taken up by hepatic scavenger cell
      populations, such as Kupffer cells, hepatic dendritic cells, stellate cells and
      liver sinusoidal endothelial cells (LSECs), can be (cross-)presented on MHC class
      I and II molecules, which leads to modulation of T cell immune functions. Among
      these cell populations, LSECs are endowed with the highest scavenger activity and
      are the most efficient cell population in cross-presenting soluble exogenous
      antigens to CD8 T cells. Together with their large number and the high cumulative
      surface area, LSECs represent the hepatic cell population that is best situated
      to interact with circulating T cells. Under physiological conditions, antigen
      specific interaction of LSECs with CD8 T cells induces tolerance that is
      characterized by nonresponsiveness towards T cell receptor-mediated stimulation.
      In contrast to functional maturation of dendritic cells by activation through
      pattern recognition receptors, there is no such maturation in antigen-presenting
      LSECs, demonstrating that even under inflammatory conditions induction of CD8 T
      cell tolerance is preserved. However, upon viral infection of LSECs, a unique
      program of T cell differentiation into effector cytotoxic T cells is initiated
      that is independent of currently known costimulatory signals. These results
      highlight specific mechanisms operative in liver-resident antigen-presenting
      cells governing the local balance between tolerance and immunity.

PMID- 21894010
TI  - Role of the hepatic parenchyma in liver transplant tolerance: a paradigm
      revisited.
AB  - Unlike other solid organs, liver transplants are spontaneously accepted in a wide
      range of animal models. In the clinic, transplanted livers also display
      privileged immunological properties allowing weaning of immunosuppression therapy
      in up to 20% of selected patients. To explain this phenomenon, many studies have
      focused on the role of donor-derived 'passenger' leukocytes that are thought to
      induce antigen-specific tolerance by migrating from the graft into recipient
      secondary lymphoid tissues. Although convincing evidence exists that these cells
      are able to elicit antiallograft T cell hyporesponsiveness, several studies argue
      against an exclusive role for this cell population and even question whether it
      is critical in conferring donor MHC-specific tolerance. Instead, these studies
      suggest that the hepatic parenchyma plays a more critical role in this
      phenomenon. In this review we will reinterpret the results of old and more recent
      literature in light of recent advances in the field of liver immunology to
      explain the contribution of both passenger leukocytes and liver tissue in the
      liver tolerance effect.

PMID- 21894011
TI  - Requirements and challenges of a preclinical autoimmune hepatitis mouse model.
AB  - Autoimmune hepatitis (AIH) is a chronic autoimmune inflammation of the liver
      usually requiring life-long immunosuppression. Steroids and azathioprin are the
      standard therapy, but the therapy is accompanied by strong side effects. Due to
      the fact that AIH is often recognized during late course of disease, it is
      difficult to obtain knowledge about the immunological mechanisms responsible for
      initiation of the disease. Current AIH models were helpful for understanding and
      modulating liver immune responses, but are not suited to study mechanisms in
      chronic AIH or to develop new therapies. While transgenic AIH models deal with
      short-term hepatitis, models with natural antigens are either self-limited or
      have unknown target antigens. Therefore, new animal models with defined onset of
      AIH and a standard course of the disease are essential for a more defined
      understanding of the disease and its pathophysiology. To obtain a preclinical
      platform for new therapeutic approaches or to be able to prevent onset of AIH, a
      positive impact of conventional standard therapeutic interventions in the model
      would be helpful. For decades, AIH research has lacked such a reliable
      preclinical model with chronic immune response against the liver. Initial results
      in breaking tolerance against hepatocytes have only led to mild and transient
      hepatitis. Transgenic models were helpful in understanding different aspects for
      hepatic immune regulation. Nowadays, the fate of T cells, especially CD8+ T
      cells, is the focus of research. Especially ignorance, anergy, deletion or TCR
      downregulation of T cells are mechanisms of tolerance against hepatic antigens.
      Furthermore, the importance of professional antigen-presenting cells and
      particularly liver sinusoidal cells in liver tolerance has been demonstrated in
      many studies. Other models have shown the mechanism of interaction of adaptive
      and innate immune cells in the liver. Recently, approaches have been made to
      establish AIH models reflecting the situation in AIH patients. This will allow
      new studies in the field and will provide an opportunity to study the onset and
      pathophysiology of AIH. Furthermore, these models will try new options for
      therapeutic approaches and might show options of how to prevent onset of disease.

PMID- 21894012
TI  - Therapeutic strategies for autoimmune hepatitis.
AB  - Autoimmune hepatitis (AIH) is a disease of unknown etiology. However, a loss of
      tolerance against the patient's own liver is regarded as the main pathogenetic
      mechanism. Immunosuppressive therapy prolongs survival in patients with severe
      AIH. Two phases of therapy have to be distinguished. In newly diagnosed AIH,
      induction of remission is the main goal. Here predniso(lo)ne alone or in
      combination with azathioprine has been shown to induce remission in the majority
      of patients. In the past, reduction of aminotransferase levels below two times
      the upper limit of normal was the aim of therapy. Nowadays, normalization of
      aminotransferase levels should be achieved. The majority of patients usually
      respond to therapy within 6-12 months. A significant reduction in
      aminotransferase levels is achieved within a few weeks of therapy. Improvement in
      clinical symptoms is followed by improvement in biochemical parameters of disease
      activity and then by significant improvement in histological disease activity.
      Around 20-40% of patients do not achieve remission. In these patients,
      alternative therapies should be evaluated for the individual patient. Prospective
      controlled trials with a larger number of patients are missing in this
      population. At the moment, mycophenolate mofetil at a dose of 2 * 1 g daily,
      either given alone or in combination with predniso(lo)ne, is able to achieve
      remission in a significant proportion of patients. Based on recent retrospective
      observations, mycophenolate mofetil is beneficial in patients who were previously
      azathioprine intolerant rather than azathioprine failure patients. Again,
      prospective trials are missing. Alternative drugs include cyclophosphamide,
      cyclosporin A, tacrolimus and others. Women in particular suffer from steroid
      specific side effects, including weight gain, moon face, diabetes, glaucoma and
      bone disease. Recently, a topical steroid, budesonide, was shown to induce
      disease remission in combination with azathioprine. The second phase of therapy
      is maintenance of remission with the lowest possible dose in order to maintain
      remission while preventing significant side effects. Careful evaluation of the
      individual patients should lead to the decision whether predniso(lo)ne,
      budesonide, azathioprine or a combination of one of the steroids with
      azathioprine is to be used to maintain remission. Recently, a study has shown
      that after 6 months of induction therapy with prednisone plus azathioprine, a
      switch to budesonide in combination with azathioprine reduced steroid-specific
      side effects while maintaining remission of liver disease. Therefore, the
      application of the topical steroids may be helpful in maintaining remission while
      reducing steroid-specific side effects. Patients with liver cirrhosis should not
      be treated with budesonide since the benefit of budesonide with its 90% pass
      effect in the liver is lost if the patient has already developed portal
      hypertension with significant portosystemic shunting. Furthermore, there are
      safety concerns regarding budesonide use in cirrhotic patients derived from
      studies in primary biliary cirrhosis. If the diagnosis is correct and the
      appropriate therapy is chosen, liver transplantation should be avoidable in
      patients with AIH.

PMID- 21894013
TI  - Success and failure of virus-specific T cell responses in hepatitis C virus
      infection.
AB  - Hepatitis C virus (HCV) infection is only cleared in a minority of infected
      individuals, the majority of patients develop chronic infection. Chronic HCV
      infection potentially leads to liver fibrosis, cirrhosis and finally
      hepatocellular carcinoma. The host immune response is an important determinant in
      the outcome of HCV infection. Innate as well as adaptive cellular and humoral
      immune responses mediate important antiviral actions; however, virus-specific T
      cell responses appear to be most critical. Indeed, strong and multispecific CD4+
      as well as CD8+ T cell responses are required for viral clearance. Interestingly,
      individuals who express certain HLA alleles (which are important for antigen
      presentation to CD4+ and CD8+ T cells) have a higher chance to clear the virus.
      The mechanisms of protection by HLA class I alleles such as HLA-B27 have been
      characterized recently. In most individuals, however, the HCV-specific immune
      response fails to clear the virus. Several mechanisms underlying this HCV
      specific T cell failure have been identified. These include viral factors such as
      viral escape mutations and immunological factors such as the expression of
      inhibitory receptors, which lead to CD8+ T cell dysfunction. An in-depth
      understanding of the determinants of success or failure of the HCV-specific T
      cell response is critical for the development of prophylactic as well as
      therapeutic vaccination regimes against HCV. Here, we will discuss the
      virological and immunological determinants of HCV clearance and persistence.

PMID- 21894014
TI  - Immune control of hepatitis B virus.
AB  - Human hepatitis B virus (HBV) infects the liver of humans or humanoid primates.
      In humans, HBV infection often causes an inflammatory liver disease - hepatitis
      B. The virus is transmitted by perinatal, percutaneous and sexual exposure, as
      well as by close person-to-person contact. The latter occurs especially among
      young children, presumably by open cuts or sores. Vertical transmission from
      mothers to their neonates, or infection during the first year of life, results in
      persistent often lifelong infection in >90% of cases. In contrast, infection
      during adulthood is cleared in >95% of cases, and results in lifelong protective
      immunity. While a correlation between the strength of HBV-specific T cell
      responses and virus clearance has been established, factors determining the
      strength of a T cell response as well as factors shifting the balance from immune
      tolerance to immune clearance are hardly understood. The innate immune response,
      early adaptive B and T cell responses, regulatory T cells, the liver
      microenvironment, and the peculiar properties of hepatocytes and nonparenchymal
      liver cells to present antigen seem to play a role. Understanding this complex
      interplay requires systematic immune monitoring of well characterized human
      cohorts, but also experimental approaches using primary human cells and
      genetically modified mouse models. Using these models, we begin to understand the
      immune recognition of HBV and how it influences the outcome of HBV infection. In
      this paper we review the current knowledge about virus-host interactions and how
      it influences the outcome of HBV infection and describe the immune signatures
      associated with clinical recovery and/or persistent infection.

PMID- 21894016
TI  - Early mechanisms of glucose improvement following laparoscopic ileal
      interposition associated with a sleeve gastrectomy evaluated by the euglycemic
      hyperinsulinemic clamp in type 2 diabetic patients with BMI below 35.
AB  - BACKGROUND: Laparoscopic ileal interposition associated with a sleeve gastrectomy
      (LII-SG) is a safe and effective operation for the treatment of type 2 diabetic
      (T2DM) patients with BMI below 35. The aim of this study was to evaluate insulin
      sensitivity (IS) and beta-cell function using the euglycemic hyperinsulinemic
      clamp (EHC) with the intravenous glucose tolerance test (IVGTT). METHODS: This
      was a prospective study of 24 T2DM patients submitted to a 3-hour EHC-IVGTT
      before and 1 month after LII-SG. Mean BMI was 29.0, mean age was 54.8 years and
      mean duration of T2DM was 10.2 years; insulin therapy was used by 62.5% of the
      patients. RESULTS: Mean BMI decreased from 29.0 to 25.8 (p < 0.001). Mean fasting
      plasma glucose and mean postprandial glucose were 202 and 251.3 mg/dl and dropped
      to 127.7 and 131.8 mg/dl (p < 0.001), respectively. Mean preoperative IS was 1.4
      mmol.min(-1).nmol(-1) and increased to 2.2 mmol. min(-1).nmol(-1) postoperatively
      (p < 0.001). Mean C-peptide AUC was 488 pmol.nmol(-1) and increased to 777 pmol.
      nmol(-1) (p = 0.37). The disposition index increased from 9.4 to 36.4
      postoperatively (p = 0.01). CONCLUSIONS: According to the clamp technique, II-SG
      significantly improved IS and beta-cell function as early as 30 days
      postoperatively in a T2DM population with a BMI of 21.9-33.8.

PMID- 21894017
TI  - Characteristics of stroke in tibet autonomous region in china: a hospital-based
      study of acute stroke.
AB  - BACKGROUND AND PURPOSE: We know little of the current status of stroke in Tibet
      Autonomous Region in China. This study was designed to investigate the
      characteristics of acute stroke in Tibet. METHODS: We conducted a hospital-based
      study on acute first-ever stroke in the People's Hospital of Tibet Autonomous
      Region (PHOTAR), and then compared the data collected to that from West China
      Hospital (WCH). RESULTS: The study included 301 inpatients from PHOTAR and 3,334
      from WCH. The peak age group in PHOTAR was one decade younger than in WCH.
      Intracerebral hemorrhage (ICH) was the main stroke subtype in PHOTAR (74.1%). The
      prevalence of hypertension and heavy alcohol consumption prior to stroke were the
      most important vascular risk factors. Treatments for stroke in PHOTAR lacked
      standardization and in-hospital mortality was higher for each subtype.
      CONCLUSIONS: ICH is the dominant stroke subtype in Tibet Autonomous Region, and
      can be attributed to high rates of hypertension and heavy alcohol consumption.
      Greater public awareness of stroke and effective management of risk factors
      should be implemented immediately in Tibet.

PMID- 21894018
TI  - Plasma viscosity in giant cell arteritis.
AB  - BACKGROUND: Diagnosis of giant cell arteritis (GCA) is based on criteria of the
      American College of Rheumatology. However, not all GCA patients meet these
      criteria and treatment may be delayed in individual patients, leading to an
      increased risk of complications. METHODS: In an observational study, we
      investigated acute phase response markers in GCA and non-GCA patients matched for
      erythrocyte sedimentation rate and CRP levels. RESULTS: Plasma viscosity (PV) was
      significantly elevated in all GCA patients, but normal in non-GCA patients.
      CONCLUSIONS: Our data suggest that PV may reflect a more specific component of
      the acute inflammatory response in patients with GCA. Analysis of PV may
      significantly contribute to a reliable diagnosis early in the course of the
      disease, particularly in patients with suspected GCA that do not meet current
      diagnostic criteria.

PMID- 21894019
TI  - The hand pronation phenomenon: a franco-german tale.
AB  - The hand pronation phenomenon due to a pyramidal tract lesion is a sign commonly
      used for identifying a mild paresis, but the first descriptions of this maneuver
      seem to have been only partially investigated by the historians of neuroscience.
      Here we illustrate that this sign was most probably originally described by Adolf
      Strumpell (1853-1925) in 1901 and subsequently re-proposed by the illustrious
      French neurologist Joseph Babinski (1857-1932) in 1907, although with a slightly
      different focus of application. Finally, the Pronationsphaenomen was analyzed in
      detail in the subsequent work of Nikolaus Gierlich (1865-1944), a less-known
      German neurologist who tried one of the first detailed reports of the
      phylogenetic significance of this sign, publishing a paper in 1925. These works
      are reported here, detailing the existing discrepancies, along with notes on the
      relevant surrounding historical context. In particular, the undervalued
      contribution of Gierlich to the history of neuroscience and to the phylogenetic
      approach to semeiotics is analyzed in more detail and acknowledged.

PMID- 21894020
TI  - Directional asymmetries of saccadic hypometria in patients with early Parkinson's
      disease and unilateral symptoms.
AB  - BACKGROUND: Saccade may be abnormal in Parkinson's disease (PD), but there have
      been no systematic studies on directional asymmetries of horizontal saccades in
      early PD. The aims of this study were to determine the saccadic abnormalities and
      their directional asymmetries. METHODS: We recorded visually guided horizontal
      prosaccades with random (random amplitudes and irregular time intervals) and
      regular (fixed amplitude and regular time interval) paradigms using video
      oculography in 44 patients with unilateral symptoms and signs from early PD and
      in 26 controls. RESULTS: PD patients showed decreased saccadic amplitude compared
      to the controls, especially during regular paradigm while the saccadic latency
      did not differ between the groups. Patients with unilateral PD tended to show
      more severe saccadic hypometria toward the symptomatic side during the regu- lar
      paradigm, compared to normal control. CONCLUSION: Even in early PD patients,
      saccadic accuracy may be abnormal. Asymmetries in saccadic hypometria are more
      likely to be detected during the anticipatable saccadic paradigm, which could be
      a useful adjunct in the diagnosis of early-stage PD.

PMID- 21894021
TI  - Enhanced-MRI and ultrasound evaluation of painful shoulder in patients after
      stroke: a pilot study.
AB  - BACKGROUND: Epidemiological and radiological studies have previously been
      performed to identify the possible causes of hemiplegic shoulder pain (HSP). Many
      different etiologies have been postulated, though no clear correlations have
      emerged, and a multifactorial pathogenesis of HSP has been proposed. Recently,
      two MRI-based studies have described different shoulder findings as possible
      causes of pain in chronic stroke survivors. PURPOSE: The aim of this study was to
      describe the structural abnormalities of the painful shoulder in the first months
      after stroke by ultrasound and enhanced MRI. The secondary aims were to identify
      possible predisposing factors for HSP and to evaluate its impact on motor
      recovery. METHODS: One hundred and fifty-three first-time stroke patients,
      admitted to the Santa Lucia Foundation for rehabilitation, were investigated for
      HSP. Twenty-five stroke patients with HSP and 16 stroke patients without shoulder
      pain were included. An ultrasound evaluation and enhanced shoulder MRI were
      performed for all the patients. RESULTS: Among the shoulder abnormalities
      detected by both imaging studies, only capsulitis, which was detected by enhanced
      shoulder MRI in 88% of the HSP patients, was independently associated with pain
      (p < 0.001) and proven to be predictive of pain intensity as expressed by the VAS
      score (p < 0.003). HSP correlated with a worse global recovery (p < 0.05) as well
      as with male sex (p = 0.006), neglect (p = 0.02) and subluxation (p = 0.03),
      although none of these features were found to be independent predictors of pain.
      CONCLUSION: Adhesive capsulitis was found to be a possible cause of HSP. However,
      MRI, which is more expensive than other diagnostic tools, may be considered the
      gold standard tool for understanding the etiology of HSP.

PMID- 21894022
TI  - Lymphocyte stimulation test for the diagnosis of non-IgE-mediated cow's milk
      allergy: a step closer to a noninvasive diagnostic tool?

PMID- 21894023
TI  - Shrimp allergy in Italian adults: a multicenter study showing a high prevalence
      of sensitivity to novel high molecular weight allergens.
AB  - BACKGROUND: Shrimp is a frequent cause of food allergy worldwide. Besides
      tropomyosin, several allergens have been described recently. OBJECTIVE: We
      investigated which allergens are involved in Italian shrimp-allergic adults.
      METHODS: Sera from 116 shrimp-allergic patients selected in 14 Italian allergy
      centers were studied. Skin prick tests with house dust mite (HDM) as well as
      measurements of IgE to Pen a 1 (shrimp tropomyosin) and whole shrimp extract were
      performed. All sera underwent shrimp immunoblot analysis, and inhibition
      experiments using HDM extract as inhibitor were carried out on some Pen a 1
      negative sera. RESULTS: Immunoblots showed much variability. IgE reactivity at
      about 30 kDa (tropomyosin) was found in <50% of cases, and reactivity at about 67
      kDa and >90 kDa was frequent. Further reactivities at 14-18, 25, 43-50, about 60
      and about 80 kDa were detected. Most subjects had a history of shrimp-induced
      systemic symptoms irrespective of the relevant allergen protein. IgE to Pen a 1
      were detected in sera from 46 (41%) patients. Skin reactivity to HDM was found in
      43/61 (70%) Pen 1-negative subjects and inhibition studies showed that pre
      adsorption of sera with HDM extract induced a marked weakening of the signal at
      >67 kDa. CONCLUSIONS: Several allergens other than tropomyosin are involved in
      shrimp allergy in adult Italian patients. Some hitherto not described high
      molecular weight allergens seem particularly relevant in this population and
      their cross-reactivity with HDM allergens makes them novel potential panallergens
      of invertebrates.

PMID- 21894024
TI  - Preliminary studies on the prevention of the ovalbumin-induced allergic response
      by Enterococcus faecalis CECT7121 in mice.
AB  - BACKGROUND: Allergic diseases are featured by an increased production of IgE due
      to an imbalance in the immune response towards a Th2 profile. In this work, the
      ability of Enterococcus faecalis CECT7121 to regulate this Th2-exaggerated
      response in a murine model of ovalbumin (OVA)-induced allergy was studied.
      METHODS: BALB/c mice intragastrically inoculated with E. faecalis CECT7121 before
      and during a subcutaneous immunization protocol with OVA were studied in
      comparison with an immunized control group. The allergen-specific immune response
      (IgE, IgG, IgG1 and IgG2a) was assessed. The proliferative activity of memory
      splenocytes and the levels of IL-4, IL-5, IL-13, IL-10, IL-12 and IFN-gamma were
      also determined. RESULTS: Upon treatment with E. faecalis CECT7121 the following
      effects were observed: (1) a decrease in specific IgE levels, (2) an increase in
      anti-OVA IgG2a levels, (3) the levels of anti-OVA IgG and IgG1 remained
      unaltered, (4) a reduction in the proliferation rate of memory cells, (5) a
      decrease in the levels of the Th2 cytokines IL-4, IL-5 and IL-13, and (6) the
      secretion of IL-10, IL-12 and IFN-gamma remained unchanged. Moreover, the
      incubation of human basophils with non-viable E. faecalis CECT7121 together with
      an allergen preparation induced the release of beta-hexosaminidase at levels that
      were lower than control reactions and similar i.g. the spontaneous release.
      CONCLUSIONS: In this model, the i.g. administration of E. faecalis CECT7121
      hampers the establishment of the OVA-induced allergic immune response, suggesting
      that this strain could be useful for the treatment of IgE-mediated allergic
      diseases.

PMID- 21894025
TI  - Effect of respiratory syncytial virus infection on plasmacytoid dendritic cell
      regulation of allergic airway inflammation.
AB  - BACKGROUND: Respiratory syncytial virus (RSV) can infect myeloid dendritic cells
      (mDCs) and regulate their function in the development of allergy. It has been
      widely reported that plasmacytoid DCs (pDCs) play a critical role in antiviral
      innate immunity. In contrast, not much is known about the role of pDCs in the
      interaction between allergy and viral infection. The purpose of the present study
      was to investigate the effect of RSV infection on pDC function in the regulation
      of allergic airway inflammation in a murine model of Dermatophagoides farinae
      sensitized allergic asthma. METHODS: Splenic pDCs isolated from D. farinae
      sensitized donor mice were infected with live RSV ex vivo. Subsequently, these
      pDCs were inoculated into the airways of D. farinae-sensitized recipient mice.
      Lung pathology, lung tissue cytokine profiles, the number of regulatory T cells
      (T(reg)) and mDCs as well as the effects of IL-10 neutralization in the lung
      tissue of recipient mice were determined. RESULTS: Intranasal inoculation of D.
      farinae-sensitized pDCs significantly inhibited the development of allergic
      airway inflammation and both Th1 and Th2 immunity. Live RSV infection of these
      pDCs prior to inoculation interfered with their inhibitory effects through
      decreasing T(reg) and IL-10 and increasing mDCs. CONCLUSIONS: In asthmatic
      airways, pDCs mediate tolerance to inhaled allergens through the regulation of
      T(reg), IL-10 and mDCs. RSV infection of pDCs potentially inhibits their
      immunotolerogenic effects and thus exacerbates allergic airway inflammation.

PMID- 21894027
TI  - Antimicrobial peptides: promising alternatives to conventional antibiotics.
AB  - Antimicrobial peptides (APs) have been described as evolutionary ancient weapons.
      Produced by a wide variety of organisms as part of a non-specific immune
      response, these peptides are involved in the direct destruction of various
      microorganisms. Several APs have been shown to have broad activity spectra
      against microorganisms such as Gram-positive and Gram-negative bacteria,
      enveloped viruses, fungi and parasites. Given that resistance to a number of
      antibiotics has developed in a wide range of microbes, the potential of APs as
      novel therapeutic agents is being evaluated. However, optimisation of APs
      designed for therapy will need to focus on such factors as their susceptibility
      to proteolytic degradation and reduction of toxicity to mammalian cells. Strict
      guidelines pertaining to their use should also be established to prevent or
      hinder future development of bacterial resistance to such peptides.

PMID- 21894026
TI  - Epitope mapping of Atlantic salmon major allergen by peptide microarray
      immunoassay.
AB  - BACKGROUND: IgE epitope mapping of allergens reveals important information about
      antigen elicitors involved in allergic reactions. The peptide-based microarray
      immunoassay offers an advantage of scale and parallel design over previous
      methods of epitope mapping. It has been used to map epitopes of some food
      allergens but has never been used with fish allergens. OBJECTIVE: We sought to
      develop a peptide microarray immunoassay to map allergenic fish epitopes of two
      isoforms of Atlantic salmon (Salmo salar) parvalbumin, Sal s 1 beta 1 and Sal s 1
      beta 2. METHODS: Sera from 16 fish-allergic patients with specific IgE to salmon
      parvalbumin were used. Twelve healthy volunteers were used as negative controls.
      A library of overlapping peptides was synthesized commercially, representing the
      primary sequence of Sal s 1 beta 1 and Sal s 1 beta 2. Peptides were used to
      analyze allergen-specific IgE antibodies by immunolabeling with patient sera.
      RESULTS: Three antigenic regions, not previously described, were identified in
      Sal s 1 beta 1. Two of them correlated with those previously reported in Gad c 1,
      parvalbumin from Baltic cod (Gadus callarias). No allergenic regions were found
      in Sal s 1 beta 2. This could be explained by crucial amino acid substitutions
      between isoforms. CONCLUSIONS: We have identified three antigenic regions in Sal
      s 1 beta 1 using a peptide microarray immunoassay. These three sequential
      epitopes formed a unique antigenic determinant in the three-dimensional model of
      the protein. In addition, we proved that isoforms from the same protein might
      have a different allergenic behavior.

PMID- 21894028
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 1: UK RRT incidence
      in 2009: national and centre-specific analyses.
AB  - INTRODUCTION: This chapter describes the characteristics of adult patients
      starting renal replacement therapy (RRT) in the UK in 2009 and the acceptance
      rates for RRT in Primary Care Trusts and Health Boards (PCT/HBs) in the UK.
      METHODS: The basic demographics and clinical characteristics are reported on
      patients starting RRT from all UK renal centres. Late presentation, defined as
      time between first being seen by a nephrologist and start of RRT being <90 days
      was also studied. Age and gender standardised ratios for acceptance rates in
      PCT/HBs were calculated. RESULTS: In 2009, the incidence rate in the UK and
      England was 109 per million population (pmp). Acceptance rates in Scotland (104
      pmp), Northern Ireland (88 pmp) and Wales (120 pmp) had all fallen although Wales
      still remained the country with the highest acceptance rate. There were wide
      variations between PCT/HBs with respect to the standardised ratios. The median
      age of all incident patients was 64.8 years (IQR 50.8, 75.1). For transplant
      centres this was 63.0 years (IQR 49.0, 74.2) and for non-transplanting centres
      66.3 years (IQR 52.6, 75.9). The median age for non-Whites was 57.1 years.
      Diabetic renal disease remained the single most common cause of renal failure
      (25%). By 90 days, 69.1% of patients were on haemodialysis, 17.7% on peritoneal
      dialysis, 6.7% had had a transplant and 6.5% had died or stopped treatment. The
      mean eGFR at the start of RRT was 8.6 ml/min/1.73 m2 which was similar to the
      previous two years. Late presentation (<90 days) has fallen from 27% in 2004 to
      19% in 2009. There was no relationship between social deprivation and
      presentation pattern. CONCLUSIONS: Acceptance rates have fallen in Northern
      Ireland, Scotland and Wales whilst they have plateaued in England over the last
      four years. Wales continued to have the highest acceptance rate of the countries
      making up the UK.

PMID- 21894029
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 6: survival and
      causes of death of UK adult patients on renal replacement therapy in 2009:
      national and centre-specific analyses.
AB  - INTRODUCTION: These analyses examine (a) survival from the start of renal
      replacement therapy (RRT), based on the total incident UK RRT population reported
      to the UK Renal Registry, including the 18% who started on PD and the 6% who
      received a pre-emptive transplant and (b) survival of prevalent patients. Changes
      in survival between 1997 and 2008 are also reported. METHODS: Survival was
      calculated for both incident and prevalent patients on RRT and compared between
      the UK countries after adjustment for age. Survival of incident patients
      (starting RRT during 2008) was calculated both from the start of RRT and amongst
      the cohort who survived at least 90 days after RRT, both with and without
      censoring at transplantation. Both Kaplan-Meier and Cox adjusted models were used
      to calculate survival. Causes of death were analysed for both groups. Relative
      risk of death was calculated compared with the general UK population. RESULTS:
      The 2008 unadjusted 1 year after 90 day survival for patients starting RRT was
      87.3%. In incident patients aged 18-64, the unadjusted 1 year survival had risen
      from 85.9% in 1997 to 91.9% in 2008 and for those aged >= 65 it had risen from
      64.2% to 75.8%. The age-adjusted one year survival (adjusted to age 60) of
      prevalent dialysis patients rose from 85% in 2000 to 89% in 2009. Diabetic
      prevalent patient one year survival rose from 76.6% in 2000 to 83.6% in 2009. The
      age-standardised mortality ratio for prevalent RRT patients compared with the
      general population was 19 at age 30 years and 2.4 at age 85 years. In the
      prevalent RRT dialysis population, cardiovascular disease accounted for 24% of
      deaths, infection 19% and treatment withdrawal 14%; 22% were recorded as
      uncertain. Treatment withdrawal was a more frequent cause of death in patients
      aged >= 65 at start of RRT than in younger patients. The median life years
      remaining for a 25-29 year old on RRT was 20 years and 4 years for a 75+ year
      old. CONCLUSIONS: Survival of patients starting RRT, has improved in the 2008
      incident cohort. The relative risk of death on RRT compared with the general
      population has fallen since 2001. Death rates on dialysis in the UK remained
      lower than when compared with a similar aged population on dialysis in the USA.

PMID- 21894030
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 7: the relationship
      between the type of vascular access used and survival in UK RRT patients in 2006.
AB  - INTRODUCTION: The type of vascular access used by haemodialysis patients is
      thought to be one of the predictors of patient survival. However, many previous
      studies have been unable to separate the effect of access type from the effects
      of other differences between patients groups or have included incident patients.
      Some centres report excellent outcomes using dialysis catheters in stable
      prevalent patients and challenge the current guidelines about the use of long
      term catheters. This is an observational UK centre level study reporting on the
      relationship between the percentage of established prevalent patients using
      definitive access and the subsequent 1 year survival. METHOD: Vascular access
      audit data from 2005 and UKRR survival data at 1 year for patients who had been
      on HD for over 3 months was obtained from the UKRR database. Regression analysis
      was used to assess the amount of variation in 1 year survival that could be
      explained by the percentage of patients using an AVF or AVG in a centre. RESULTS:
      From the renal centres reporting to the UKRR in 2005, 16,984 patients had
      vascular access data. The mean centre level 1 year survival was 86.4% (95% CI:
      82.2-90.9) and was 86.9% (95% CI: 82.8-91.2) after censoring for transplantation.
      The mean percentage of haemodialysis patients using definitive access (AVF or
      AVG) in a centre was 69.8% (SD 10.4). A small positive association was found
      between the percentage of HD patients using an AVF or AVG in a centre and 1 year
      uncensored survival (beta = 0.06, p = 0.04). The type of access in use was able
      to explain 6% of the variation in centre level survival. CONCLUSIONS: To some
      extent, this study has repeated work done by DOPPS and in the US but for the
      first time has studied only prevalent dialysis patients and looked at the UK
      dialysis population. Whilst increased venous catheter use was associated with an
      increase in one year mortality of prevalent established haemodialysis patients,
      this effect was very small and only accounted for some 6% of the variation in one
      year mortality between renal centres. Further work using data from the current
      large vascular access audit needs to be done to further elucidate best practice
      within the UK.

PMID- 21894031
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 8: adequacy of
      haemodialysis in UK adult patients in 2009: national and centre-specific
      analyses.
AB  - BACKGROUND: Outcome in patients treated with haemodialysis (HD) is influenced by
      the delivered dose of dialysis. The UK Renal Association (RA) publishes Clinical
      Practice Guidelines which include recommendations for dialysis dose. The urea
      reduction ratio (URR) is a widely used measure of dialysis dose. AIM: To
      determine the extent to which patients received the recommended dose of HD in the
      UK. METHODS: All seventy-two UK renal centres submitted data to the UK Renal
      Registry (UKRR). Two groups of patients were included in the analyses: the
      prevalent patient population on 31st December 2009 and the incident patient
      population for 2009. Centres returning data on <50% of their patient population
      were excluded from centre-specific comparisons. RESULTS: Data regarding URR were
      available from 63 renal centres in the UK. Fifty-one centres provided URR data on
      more than 90% of prevalent patients. The proportion of patients in the UK who met
      the UK Clinical Practice Guideline for URR (>65%) increased from 56% in 1998 to
      85.5% in 2009. There was considerable variation between centres, with 19 centres
      attaining the RA clinical practice guideline in >90% of patients and 5 centres
      attaining the guideline in <70% of patients. The delivered HD dose (URR) was
      lower in patients who had just commenced dialysis treatment compared to patients
      who had survived longer on HD. CONCLUSIONS: The delivered dose of HD for patients
      with established renal failure has increased over the last decade. Whilst the
      majority of UK patients achieved the target URR there was considerable variation
      between centres in the percentage of patients achieving the guideline.

PMID- 21894032
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 9: haemoglobin,
      ferritin and erythropoietin amongst UK adult dialysis patients in 2009: national
      and centre-specific analyses.
AB  - BACKGROUND: The UK Renal Association (RA) and National Institute for Health and
      Clinical Excellence (NICE) have published Clinical Practice Guidelines which
      include recommendations for management of anaemia in established renal failure.
      AIMS: To determine the extent to which the guidelines for anaemia management are
      met in the UK. METHODS: Quarterly data were obtained regarding haemoglobin (Hb)
      and factors that influence Hb from renal centres in England, Wales, Northern
      Ireland (EWNI) and the Scottish Renal Registry for the incident and prevalent
      renal replacement therapy (RRT) cohorts for 2009. RESULTS: In the UK, in 2009 55%
      of patients commenced dialysis therapy with Hb x10.0 g/dl (median Hb 10.2 g/dl).
      The median Hb of haemodialysis (HD) patients was 11.6 g/dl with an interquartile
      range (IQR) of 10.6 - 12.4 g/dl. Of HD patients 85% had Hb >= 10.0 g/dl. The
      median Hb of peritoneal dialysis (PD) patients in the UK was 11.7 g/dl (IQR 10.7
      12.6 g/dl). Of UK PD patients, 88% had Hb >= 10.0 g/dl. The median ferritin in HD
      patients in EWNI was 441 mg/L (IQR 289-629) and 96% of HD patients had a ferritin
      >= 100 mg/L. The median ferritin in PD patients was 249 mg/L (IQR 142-412) with
      86% of PD patients having a ferritin 5100 mg/L. In EWNI the mean Erythropoietin
      Stimulating Agent (ESA) dose was higher for HD than PD patients (9,507 vs. 6,212
      IU/week). CONCLUSIONS: In 2009, 56% of prevalent HD patients had a Hb >= 10.5 and
      <= 12.5 g/dl compared with 54% in 2008 and 53% in 2007. Fifty-four percent of
      prevalent PD patients had a Hb >=10.5 and <=12.5 g/dl compared to 55% in 2008.

PMID- 21894033
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 10: calcium,
      phosphate, parathyroid hormone, bicarbonate and total cholesterol concentrations
      amongst patients receiving haemodialysis or peritoneal dialysis in England, Wales
      and Northern Ireland in 2009: national and centre-specific analyses.
AB  - INTRODUCTION: The UK Renal Association Clinical Practice Guidelines include
      clinical performance measures for biochemical variables in dialysis patients [1].
      The UK Renal Registry (UKRR) annually audits dialysis centre performance against
      these measures as part of its role in promoting continuous quality improvement.
      METHODS: Cross sectional performance analyses were undertaken to compare dialysis
      centre achievement of clinical audit measures for prevalent haemodialysis (HD)
      and peritoneal dialysis (PD) cohorts in 2009. The biochemical variables studied
      were phosphate, adjusted calcium, parathyroid hormone, bicarbonate and total
      cholesterol. In addition longitudinal analyses were performed (2000-2009) to show
      changes in achievement of clinical performance measures over time. RESULTS: Sixty
      one percent of HD and 70% of PD patients had phosphate between 1.1-1.8 mmol/L.
      Seventy-four percent of HD and 75% of PD patients had adjusted calcium between
      2.2-2.5 mmol/L. Twenty-eight percent of HD and 32% of PD patients had parathyroid
      hormone between 16-32 pmol/L. Seventy-two percent of HD and 83% of PD patients
      achieved the audit measure for bicarbonate. There was significant inter-centre
      variation for all variables studied. CONCLUSIONS: The UKRR consistently
      demonstrates significant inter-centre variation in achievement of biochemical
      clinical audit measures. Understanding the causes of this variation is an
      important part of improving the care of dialysis patients in the UK.

PMID- 21894034
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 11: blood pressure
      profile of prevalent patients receiving renal replacement therapy in England,
      Wales and Northern Ireland in 2009: national and centre-specific analyses.
AB  - BACKGROUND: The UK Renal Registry (UKRR) assesses blood pressure (BP) control
      annually for patients receiving Renal Replacement Therapy (RRT) at renal centres
      in England, Wales and Northern Ireland. METHODS: Patients alive and receiving RRT
      on 31st December 2009 with a BP reading in either the fourth or third quarter of
      2009 were included. Summary statistics were calculated for each renal centre and
      country. RESULTS: Data completeness for BP measurements submitted to the UKRR for
      all modalities improved from the previous year and was better for HD patients
      (67% for pre-HD measurements) than for PD patients (44%) or transplant recipients
      (37%). In 2009, the median pre-and post-HD SBP were 142 mmHg and 129 mmHg
      respectively. The median SBP of patients on PD was 137 mmHg. Transplant
      recipients had a median SBP of 134 mmHg. Median DBP were 74 mmHg (pre-HD), 68
      mmHg (post-HD), 79 mmHg (PD) and 79 mmHg (transplant). Only 26.7% of PD patients
      achieved the Renal Association guideline of SBP <130 mmHg and DBP <80 mmHg.
      Amongst transplant patients, 27.2% achieved the Renal Association guideline of
      SBP <130 mmHg and DBP <80 mmHg. CONCLUSION: In 2009 there continued to be
      significant variation in the achievement of BP standards between UK renal
      centres.

PMID- 21894035
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 12: clinical,
      haematological and biochemical parameters in patients receiving renal replacement
      therapy in paediatric centres in the UK in 2009: national and centre-specific
      analyses.
AB  - BACKGROUND: The British Association for Paediatric Nephrology Registry was
      established fifteen years ago to analyse data related to renal replacement
      therapy for children. The registry receives data from the 13 paediatric
      nephrology centres in the UK. In 2008 the registry was relocated to the UK Renal
      Registry (UKRR). AIM: To provide centre specific data so that individual centres
      can reflect on the contribution that their data makes to the national picture and
      to determine the extent to which their patient parameters meet nationally agreed
      audit standards for the management of children with established renal failure.
      METHOD: Data were submitted by either paper or electronic returns. Data were
      analysed to calculate summary statistics and where applicable the percentage
      achieving an audit standard. The standards used were those set out by the Renal
      Association and the National Institute for Health and Clinical Excellence.
      RESULTS: Data were received from all but one centre. Anthropometric data
      confirmed that children with established renal failure (ERF) in the UK are short
      compared with their peers with no change in recent trends. In the UK as a whole,
      the control of blood pressure, anaemia and bone biochemistry is suboptimal.
      CONCLUSIONS: Key features of this report are the provision of centre specific
      data and comparison of data to audit standards. It is hoped that this information
      will provide a basis for discussion and a stimulus to improve the care of
      children with ERF.

PMID- 21894036
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 13: centre
      variation in access to renal transplantation in the UK (2004-2006).
AB  - BACKGROUND: Renal transplantation is recognised as being the optimal treatment
      modality for many patients with end stage renal disease. This analysis aimed to
      explore the equity of access to renal transplantation in the UK. METHODS:
      Transplant activity and waiting list data were obtained from NHS Blood and
      Transplant, demographic and laboratory data were obtained from the UK Renal
      Registry. All incident RRT patients starting treatment between 1st January 2004
      and 31st December 2006 from 65 renal centres were considered for inclusion. The
      cohort was followed until 31st December 2008 (or until transplantation or death,
      whichever was earliest). RESULTS: Age, ethnicity and primary renal diagnosis were
      associated with both accessing the kidney transplant waiting list and receiving
      an organ. A patient starting dialysis in a non-transplanting renal centre was
      less likely to be registered for transplantation (OR 0.90, 95% CI 0.82-0.99) or
      receive a transplant from a donor after cardiac death or a living kidney donor
      (OR 0.69, 95% CI 0.60-0.79) compared with patients cared for in transplanting
      renal centres. Once registered for kidney transplantation, patients in both
      transplanting and nontransplanting renal centres had an equal chance of receiving
      a transplant from a donor after brain stem death (OR 0.92, 95% CI 0.78-1.08).
      CONCLUSION: There is wide variation in access to kidney transplantation between
      UK renal centres which cannot be explained by differences in case mix.

PMID- 21894037
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 14: enhancing
      access to UK Renal Registry data through innovative online data visualisations.
AB  - INTRODUCTION: As the volume of data and analyses grows with time, so does the
      need to present this increasingly complex information in an accessible and
      clinically informative manner which is responsive to, and reflects the nature of,
      the enquiries made by those seeking to access the data. THE UK RENAL REGISTRY
      INTERACTIVE DATA PORTAL: The UK Renal Registry (UKRR) now has a bespoke
      interactive data portal which provides a focussed point of access to a variety of
      graphical display formats and analyses of UKRR data including: . Centre-specific
      reports--a distillation of annual UKRR data including a colour-coded dashboard
      summary as well as both funnel plots and longitudinal statistical process control
      charts for a range of clinical parameters. . Interactive flash-based longitudinal
      Statistical Process Control charts on a per-centre and per-parameter basis
      allowing for a more detailed review of performance over time. These charts are
      the interactive correlates of those available in the centre-specific reports. .
      Rosling/Gapminder-style motion charts on a perparameter basis simultaneously
      detailing performance and activity data from multiple centres interactively over
      time (more details below). . An interactive graphical pivot chart solution using
      OLAP technology allowing users to design and export their own charts/analyses in
      real-time using UKRR data. CONCLUSION: This work builds strongly on the wealth of
      information arising from the high-quality validated UKRR datasets. The portal
      will empower and engage the UK renal community in the comparative analysis of
      delivered renal care ultimately leading to enhanced quality improvement over
      time.

PMID- 21894038
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 15: UK renal centre
      survey results 2010: RRT incidence and use of home dialysis modalities.
AB  - INTRODUCTION: RRT incidence rates and the proportion of patients using a home
      dialysis modality (peritoneal or home haemodialysis) varies widely between
      centres and persists even after area differences in age, ethnicity and social
      deprivation structure are taken into account. A nationwide survey was undertaken
      to identify possible drivers of this variation. METHODS: A systematic literature
      review followed by a two-stage Delphi consensus technique was employed to
      identify renal centre characteristics and practice patterns that may be important
      in determining either RRT incidence or home modality usage. RESULTS: All 72
      (100%) of UK adult renal centres responded. Questions about staffing numbers,
      interface with primary care, interface with other secondary care sites, capacity
      within the HD programme, constituents of pre-dialysis education programmes,
      conservative management programmes, range of treatments available, dialysis
      access and training and physician attitudes to home modalities were included.
      CONCLUSIONS: There was wide variation in practice patterns and centre
      characteristics across the UK. Overall, physician enthusiasm for home dialysis
      modalities was greater than the actual usage of home dialysis.

PMID- 21894039
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 16: memories of
      changes in renal care over three decades--the human perspective on registry
      statistics.
AB  - INTRODUCTION: This is a personal memory of 35 years of renal replacement therapy
      charting the changes in care through that time. METHOD: The personal
      reminiscences were augmented by the recollections of other patients and staff
      from the time. RESULTS: Major changes are charted in: the selection of patients
      especially children, the care of children, approaches to diet, methods of
      dialysis, transplant techniques and immunosuppression. Attitudes towards care and
      lifestyle possibilities have become more liberal for patients. CONCLUSION: Much
      has changed, mainly for the better and some old ideas have come back into
      fashion. Long-term patients have been through very difficult experiences and
      might have strongly formed opinions about their treatment as a result: perhaps
      staff should listen to these patients and learn from their wealth of experience.

PMID- 21894040
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 2: UK RRT
      prevalence in 2009: national and centre-specific analyses.
AB  - INTRODUCTION: This chapter describes the characteristics of adult patients on
      renal replacement therapy (RRT) in the UK in 2009. The prevalence rates per
      million population (pmp) were calculated for Primary Care Trusts in England,
      Health and Social Care Areas in Northern Ireland, Local Health Boards in Wales
      and Health Boards in Scotland. These areas will be referred to in this report as
      'PCT/HBs'. METHODS: Data were electronically collected from all 72 renal centres
      within the UK. A series of cross-sectional and longitudinal analyses were
      performed to describe the demographics of prevalent RRT patients in 2009 at
      centre and national level. Age and gender standardised ratios for prevalence
      rates in PCT/HBs were calculated. RESULTS: There were 49,080 adult patients
      receiving RRT in the UK on 31st December 2009, equating to a UK prevalence of 794
      pmp. This represented an annual increase in prevalent numbers of approximately
      3.2% although there was significant variation between centres and PCT/HB areas.
      The growth rate from 2008 to 2009 for prevalent patients by treatment modality in
      the UK was 4.2% for haemodialysis (HD), a fall of 7.2% for peritoneal dialysis
      (PD) and a growth of 4.4% with a functioning transplant. There has been a slow
      but steady decline in the proportion of PD patients from 2000 onwards. Median RRT
      vintage was 5.4 years. The median age of prevalent patients was 57.7 years (HD
      65.9 years, PD 61.2 years and transplant 50.8 years). For all ages, prevalence
      rates in males exceeded those in females: peaks for males were in the 75-79 years
      age group at 2,632 pmp and for females in the 70-74 years age group at 1,445 pmp.
      The most common identifiable renal diagnosis was biopsy-proven glomerulonephritis
      (16.0%), followed by diabetes (14.7%). Transplantation was the most common
      treatment modality (48%), HD in 44% and PD 8%. However, HD was increasingly
      common with increasing age and transplantation less common. CONCLUSIONS: The HD
      and transplant population continued to expand whilst the PD population
      contracted. There were national, regional and dialysis centre level variations in
      prevalence rates. This has implications for service planning and ensuring equity
      of care for RRT patients.

PMID- 21894041
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 3: demographic and
      biochemistry profile of kidney transplant recipients in the UK in 2009: national
      and centre-specific analyses.
AB  - INTRODUCTION: National transplant registries routinely focus on centre-specific
      patient and graft survival rates following renal transplantation. However other
      outcomes such as graft function (as measured by eGFR), haemoglobin, biochemical
      variables and blood pressure are also important quality of care indicators.
      METHODS: Renal transplant activity, incident graft survival data and donor
      information were obtained from NHS Blood and Transplant. Laboratory and clinical
      variables and prevalent survival data were obtained from the UK Renal Registry.
      Data were analysed separately for prevalent and one year post-transplant
      patients. RESULTS: Increasing live and donor after cardiac death donors were
      responsible for the increasing transplant activity within the UK. During 2009,
      2.9% of prevalent transplant patients experienced graft failure and transplant
      patient death rates remained stable at 2.5 per 100 patient years. There was
      centre variation in outcomes including eGFR, haemoglobin and biochemical
      variables in prevalent and 1 year posttransplant patients. Analysis of prevalent
      transplants by chronic kidney disease stage showed 14.3% with an eGFR <30
      ml/min/1.73 m(2) and 1.9% with an eGFR <15 ml/min/1.73 m(2). Of those with CKD
      stage 5T, 33.3% had haemoglobin concentrations <10.5 g/dl, 22.4% phosphate
      concentrations >= 1.8 mmol/L and 7.7% adjusted calcium concentrations >= 2.6
      mmol/L. CONCLUSION: Significant variations in clinical outcomes (unadjusted for
      patient-specific variables) amongst kidney transplant recipients continued to
      exist in the UK, and may reflect differences in healthcare delivery between renal
      centres.

PMID- 21894042
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 4: comorbidities
      and current smoking status amongst patients starting renal replacement therapy in
      England, Wales and Northern Ireland from 2008 to 2009.
AB  - INTRODUCTION: Comorbidity is an important determinant of survival for renal
      replacement therapy patients and impacts other care processes such as dialysis
      access creation and transplant wait-listing. The prevalence of comorbidities in
      incident patients on renal replacement therapy (RRT) changes with age and varies
      between ethnic groups. This study describes these associations and the
      independent effect of comorbidities on outcomes. METHODS: Incident patients
      reported to the UK Renal Registry (UKRR) with comorbidity data in 2008 and 2009
      (n = 5,617) were included in analyses exploring the association of comorbidity
      with patient demographics, treatment modality, haemoglobin and renal function at
      start of RRT. For analyses examining comorbidity and survival, adult patients
      starting RRT between 2004 and 2009 in centres reporting to the UKRR with
      comorbidity data (n = 16,527) were included. The relationship between
      comorbidities and mortality at 90 days and one year after 90 days from start of
      RRT was explored using Cox regression. RESULTS: Completeness of comorbidity data
      was 44.4% in 2009 compared with 52.1% in 2004. Of patients with data, 56.5% had
      one or more comorbidities. Diabetes mellitus and ischaemic heart disease were the
      most common conditions seen in 32.9% and 22.5% of patients respectively. Current
      smoking was recorded for 12.4% of incident RRT patients in the 2-year period. The
      presence of comorbidities in patients <75 years became more common with
      increasing age in all ethnic groups. In multivariable survival analysis,
      malignancy and the presence of ischaemic/neuropathic ulcers were the strongest
      independent predictors of poor survival at 1 year after 90 days from the start of
      RRT in patients <65 years. CONCLUSION: Differences in prevalence rates of
      comorbid illnesses in incident RRT patients may reflect variation in access to
      health care or competing risk prior to commencing treatment. The interpretation
      of analyses continues to be limited by poor data completeness.

PMID- 21894043
TI  - UK Renal Registry 13th Annual Report (December 2010): Chapter 5: demography of
      the UK paediatric renal replacement therapy population in 2009.
AB  - AIMS: To describe the demographics of the paediatric RRT population under the age
      of 16 years in the UK and to analyse changes in demography with time. METHODS:
      Extraction and analysis of data from the UK Renal Registry (UKRR). RESULTS: There
      were 751 children <16 years old with established renal failure (ERF) in the UK in
      December 2009. The reported prevalence under the age of 16 years was 65 per
      million age related population (pmarp) and the reported incidence 9.3 pmarp. The
      incidence and prevalence for South Asian patients was much higher than that of
      the White and Black populations. Of the patients for whom a primary renal
      diagnosis had been reported, renal dysplasia +/- reflux was the most common cause
      of ERF accounting for 34.0% of prevalent cases. There has been growth in
      treatment numbers in all paediatric renal centres between 1995 and 2010. Whilst
      the rate of transplantation within 90 days of commencing RRT has remained at
      around 25-30% of patients, the use of HD has increased by 4% at the expense of
      PD. CONCLUSIONS: The paediatric ERF population continued to expand with a slow
      increase in both incidence and prevalence rates. The high incidence in patients
      from ethnic minority groups will lead to a greater proportion of the population
      being from these groups in time. To maintain the high proportion of engrafted
      patients it will be necessary to encourage living donation in the ethnic minority
      population.

PMID- 21894044
TI  - Application of beta regression to analyze ischemic stroke volume in NINDS rt-PA
      clinical trials.
AB  - BACKGROUND AND PURPOSE: Ischemic stroke lesion volumes have proven difficult to
      analyze due to the extremely skewed shape of their underlying distribution. We
      introduce an extension of generalized linear models, beta regression, as a
      possible method of modeling extremely skewed distributions as evidenced in
      ischemic stroke lesion volumes. METHODS: The NINDS rt-PA clinical trials measured
      ischemic stroke lesion volume as a secondary trial outcome. Three-month lesion
      volumes from these trials were analyzed using beta regression. A multi-variable
      regression model associating explanatory variables with ischemic stroke lesion
      volumes was constructed using accepted model building strategies and compared
      with the previously published volumetric analysis. RESULTS: Beta regression
      produced a similar model when compared to the previous analysis published by the
      study group. All previously identified variables of importance were detected in
      the model building process. The age by treatment interaction described in
      previous studies was also found in this analysis, confirming the strong effect
      age has on stroke outcomes. Further, a treatment effect was elicited in terms of
      odds ratios, yielding a previously unknown quantification of the effect of rt-PA
      on lesion volumes. CONCLUSIONS: Beta regression proved adept in modeling ischemic
      stroke lesions and offered the interpretation of covariates in terms of odds
      ratios. Beta regression is seen as a legitimate alternative to analyze ischemic
      stroke volumes.

PMID- 21894046
TI  - Perception of recurrent stroke risk among stroke survivors.

PMID- 21894045
TI  - Perception of recurrent stroke risk among black, white and Hispanic ischemic
      stroke and transient ischemic attack survivors: the SWIFT study.
AB  - OBJECTIVES: Risk modification through behavior change is critical for primary and
      secondary stroke prevention. Theories of health behavior identify perceived risk
      as an important component to facilitate behavior change; however, little is known
      about perceived risk of vascular events among stroke survivors. METHODS: The
      SWIFT (Stroke Warning Information and Faster Treatment) study includes a
      prospective population-based ethnically diverse cohort of ischemic stroke and
      transient ischemic attack survivors. We investigate the baseline relationship
      between demographics, health beliefs, and knowledge on risk perception.
      Regression models examined predictors of inaccurate perception. RESULTS: Only 20%
      accurately estimated risk, 10% of the participants underestimated risk, and 70%
      of the 817 study participants significantly overestimated their risk for a
      recurrent stroke. The mean perceived likelihood of recurrent ischemic stroke in
      the next 10 years was 51 +/- 7%. We found no significant differences by race
      ethnicity with regard to accurate estimation of risk. Inaccurate estimation of
      risk was associated with attitudes and beliefs [worry (p < 0.04), fatalism (p <
      0.07)] and memory problems (p < 0.01), but not history or knowledge of vascular
      risk factors. CONCLUSION: This paper provides a unique perspective on how factors
      such as belief systems influence risk perception in a diverse population at high
      stroke risk. There is a need for future research on how risk perception can
      inform primary and secondary stroke prevention.

PMID- 21894047
TI  - Tremor in school-aged children: a cross-sectional study of tremor in 819 boys and
      girls in Burgos, Spain.
AB  - BACKGROUND: Mild hand tremor occurs in most normal adults. There are no surveys
      of the prevalence or clinical correlates of such tremor among children. METHODS:
      A cross-sectional study of tics, tremor and other neurological disorders was
      conducted in Spanish children; thus, 819 schoolchildren in Burgos, Spain, drew
      Archimedes spirals with each hand. Tremor in spirals was rated (0-2) by a blinded
      neurologist and an overall tremor rating (0-4) was assigned. RESULTS: The mean
      age was 10.9 +/- 3.1 years. A tremor rating of 1 (mild tremor) was present in
      either hand in 424 (51.7%) children, and in both hands in 88 (10.7%) children.
      Higher tremor ratings were very uncommon. The overall tremor rating was higher in
      boys than girls (1.31 +/- 0.41 vs. 1.22 +/- 0.34, p = 0.002) and correlated
      weakly yet significantly with age (rho = 0.09, p = 0.01). Within subjects, the
      left hand spiral rating was greater than the right (p < 0.001). CONCLUSIONS: In
      this cross-sectional study of 819 Spanish schoolchildren, mild tremor was
      commonly observed. As in adults, males had more tremor than females, tremor
      scores increased with age, and tremor scores were higher in the left than right
      arm, demonstrating that these clinical correlations seem to be more broadly
      generalizable to children. The functional significance of tremor in children,
      particularly as it relates to handwriting proficiency, deserves additional
      scrutiny.

PMID- 21894048
TI  - Use of predictive markers in oncology: are phase 3 trials always required?

PMID- 21894049
TI  - KRAS mutation in metastatic pancreatic ductal adenocarcinoma: results of a
      multicenter phase II study evaluating efficacy of cetuximab plus
      gemcitabine/oxaliplatin (GEMOXCET) in first-line therapy.
AB  - BACKGROUND: Genetic alterations within the epidermal growth factor receptor
      (EGFR) pathway, including KRAS mutations, have been demonstrated to be associated
      with response to EGFR inhibitors like cetuximab in colorectal cancers. Mutations
      in the KRAS gene have been found in 70-90% of pancreatic cancers. Unfortunately,
      the addition of cetuximab to chemotherapy did not increase response or survival
      in patients with advanced pancreatic cancer in phase II and phase III studies.
      The aim of this study was to evaluate the relationship between KRAS mutations and
      response or survival in patients with metastatic pancreatic cancer treated with
      cetuximab plus chemotherapy. METHODS: Within a multicenter phase II trial, 64
      patients with metastatic pancreatic cancer were treated with cetuximab in
      combination with gemcitabine and oxaliplatin until disease progression. Analyses
      of the EGFR pathway, including KRAS mutations, could be performed in 25 patients.
      Analyses were carried out following microdissection of the tumor. RESULTS:
      Fourteen (56%) of the 25 patients examined harbored a point mutation in codon 12
      of the KRAS gene. No differences between the groups were noted in median
      progression-free survival (104 days in KRAS wild-type patients vs. 118 days in
      patients with KRAS mutations). Overall survival was longer in wild-type patients
      compared to patients with KRAS mutations (263 vs. 162 days), but the difference
      did not reach statistical significance. A further analysis of our clinical phase
      II trial showed that the presence of a rash was significantly correlated with
      overall survival. CONCLUSIONS: KRAS mutation in codon 12 may be associated with
      reduced survival compared to KRAS wild type. The role of KRAS mutations for
      cetuximab therapy in pancreatic cancer warrants further investigation in larger
      trials to exclude an epiphenomenon. Furthermore, the development of a rash is
      indicative of clinical benefit.

PMID- 21894050
TI  - Benzodiazepine use in breast cancer survivors: findings from a consecutive series
      of 1,000 patients.
AB  - OBJECTIVE: This study reports the percentage of breast cancer survivors receiving
      ongoing benzodiazepines and the circumstances surrounding their usage. METHODS:
      The medical records of 1,000 consecutive breast cancer survivors who were no
      longer receiving adjuvant chemotherapy were reviewed. RESULTS: Among those
      patients, 7.9% (95% confidence interval 6.2-9.6; higher than the 3% rate in the
      general population) were receiving benzodiazepines. Lorazepam was most commonly
      prescribed. Sixty-eight patients were cancer free at their last visit, and 51 had
      not been taking benzodiazepines prior to their cancer diagnosis. Anxiety was the
      single most frequent reason for initiating and continuing benzodiazepines.
      CONCLUSION: Anxiety appears to be a common explanation for relatively high rates
      of benzodiazepine use in breast cancer survivors. This finding merits further
      study.

PMID- 21894051
TI  - A study on orbital volume of Korean people in their 20s or 40s.
AB  - AIMS: To measure the orbital volume of normal Korean people in two different age
      groups (subjects were in their 20s or 40s), and analyze the differences of
      orbital volume with respect to age and gender. In addition, to analyze
      correlation between body parameters (height and weight) and the orbital volume.
      METHODS: Magnetic resonance imaging (MRI) data were acquired for a total of 143
      subjects, consisting of 71 subjects in their 20s (32 males and 39 females) and 72
      subjects in their 40s (30 males and 42 females). Two-way ANOVA was used to
      analyze how orbital volume changes with respect to gender and age. A multiple
      regression analysis was performed to investigate the correlation between body
      parameters and the orbital volume. RESULTS: The orbital volume of subjects in
      their 20s was larger than that of subjects in their 40s, and the volume was
      larger in men than in women. As age increased, the decrease in the orbital volume
      of women was greater than that of men. While weight and height showed positive
      correlations with orbital volume in male and female subjects in their 20s,
      respectively, weight showed a positive correlation with orbital volume in male
      and female subjects in their 40s. CONCLUSIONS: These results provide basic
      information about the effect of age, gender, and body parameters on orbital
      volume of Korean people in their 20s or 40s.

PMID- 21894052
TI  - Chronic serous otitis media as a manifestation of temporal meningioma.
AB  - Chronic serous otitis media is a common problem in the daily routine of the
      otorhinolaryngologist. In the majority of cases, the cause is related to
      dysfunction of the eustachian tube due to viral or bacterial rhinitis and
      occasionally to nasopharyngeal tumors. We report a case of a patient presenting
      with chronic serous otitis media that was resistant to conventional therapy. MRI
      with gadolinium finally revealed that the middle ear fluid was caused by leakage
      of cerebrospinal fluid (CSF) due to bone destruction by a temporal meningioma.
      The CSF leakage was closed by surgery. Histopathology confirmed meningioma in the
      temporal bone.

PMID- 21894053
TI  - Acute pancreatitis: mild, severe or potentially fatal.

PMID- 21894054
TI  - Oral cholecalciferol versus ultraviolet radiation B: effect on vitamin D
      metabolites in patients with chronic pancreatitis and fat malabsorption - a
      randomized clinical trial.
AB  - BACKGROUND: Patients with chronic pancreatitis (CP) often develop fat
      malabsorption and are susceptible to hypovitaminosis D. AIM: We wanted to
      evaluate the intestinal uptake of cholecalciferol in patients with CP and fat
      malabsorption. METHODS: We did a prospective placebo-controlled study including
      patients with verified CP and fat malabsorption. They were randomized to 10 weeks
      of (A) ultraviolet radiation B (UVB) 6 min weekly in a commercial tanning bed,
      (B) vitamin D supplement 1,520 IU/daily, or (C) placebo. The vitamin D
      metabolites 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (calcitriol)
      were quantified at the start and end of the study. RESULTS: In total 30 patients
      were randomized and 27 completed the study. Compliance to tablets and tanning
      sessions was >80%. The changes in 25OHD levels in group B (32.3 nmol/l; 95% CI 15
      50) were significantly greater than changes in group A (p < 0.001) and group C (p
      < 0.001). Changes in group A (1.1 nmol/l) did not differ from the placebo group
      (p = 0.9). Changes in calcitriol levels were identical between groups.
      CONCLUSIONS: Daily vitamin D supplements increased 25OHD in patients with CP
      compared to placebo whereas weekly tanning bed sessions did not.

PMID- 21894055
TI  - Surgical treatment of pancreatic tumors in childhood and adolescence: uncommon
      neoplasms with favorable outcome.
AB  - BACKGROUND/AIMS: Pancreatic tumors in children and adolescents are uncommon. The
      aim of the present paper was to analyze short- and long-term outcomes after
      surgical treatment of primary pancreatic neoplasms in children and adolescents at
      a single high-volume center for pancreatic diseases. METHODS: Retrospective
      review of medical records and pathology reports of patients younger than 18 years
      who underwent surgery at Verona University Hospital from 1990 through 2010.
      RESULTS: The study population consisted of 20 patients. Abdominal pain and
      palpable mass were the most common presenting symptoms. No patient had a locally
      advanced, unresectable or metastatic disease. Complete resection (R0) was
      achieved in 19 patients. There was no postoperative mortality, but postoperative
      complications occurred in 5 cases (25%). Histological examination showed 12 solid
      pseudopapillary tumors, 5 neuroendocrine tumors, 2 cystadenomas and 1 epithelial
      malignant tumor. At a median follow-up of 49.5 months (range: 7-234), there was
      no tumor recurrence. Postoperative diabetes was diagnosed in 1 patient and 4
      other patients developed pancreatic exocrine insufficiency. CONCLUSION: In the
      setting of a high-volume surgical center, radical resection of pancreatic tumors
      in children and adolescents is associated with acceptable postoperative morbidity
      and favorable long-term outcome.

PMID- 21894056
TI  - Role of endoscopic ultrasound and endoscopic ultrasound-guided fine-needle
      aspiration in diagnosing metastasis to the pancreas: a tertiary center
      experience.
AB  - BACKGROUND: Metastasis to the pancreas (MP) is a rare entity that is difficult to
      identify by imaging alone. Few reports have described endoscopic ultrasound (EUS)
      and EUS-guided fine-needle aspiration (FNA) findings. Herein, we try to describe
      the EUS and EUS-FNA characteristics of MP. METHODS: This retrospective study
      compared 28 patients with MP (13 males; mean age: 60.1 +/- 12.6 years) and 60
      control patients (30 males; 62.7 +/- 11.5 years) with pancreatic ductal
      adenocarcinoma (PDAC). All lesions were characterized by EUS, and MP was
      diagnosed by EUS-FNA (n = 16), surgery (n = 6) or both (n = 6). RESULTS:
      Multivariate logistic regression revealed that the presence of regular borders (p
      = 0.004; OR: 8.81, 95% CI: 1.97-39.4), the absence of retention cysts (p = 0.045;
      OR: 12.5, 95% CI: 1.06-147.0), and the absence of main pancreatic duct (MPD)
      dilation (p = 0.003; OR: 8.18, 95% CI: 2.04-32.8) were predictors of MP rather
      than PDAC. The EUS-FNA sampling adequacy was 95.4% (21/22), and the correct
      diagnosis was obtained in 95.2% (20/21) of cases when K-ras mutation analysis
      and/or immunostaining were added. CONCLUSION: The presence of regular borders,
      the absence of retention cysts and the presence of nondilated MPD on EUS indicate
      MP rather than PDAC. This diagnosis can be accurately confirmed by EUS-FNA with
      immunostaining and/or K-ras analysis.

PMID- 21894057
TI  - Risk factors for postendoscopic retrograde cholangiopancreatography pancreatitis:
      a retrospective analysis of 7,168 cases.
AB  - BACKGROUND AND AIMS: Postendoscopic retrograde cholangiopancreatography
      pancreatitis (PEP) is one of the most common and serious complications after
      endoscopic retrograde cholangiopancreatography (ERCP). This study aims to test
      the hypothesis that the incidence of PEP declined over time due to improved
      patient selection and/or endoscopic equipment and endoscopic techniques.
      Therefore, we compared the incidence and risk factors of PEP between four
      arbitrary chronologically stratified groups. METHODS: A total of 7,168 cases of
      ERCP procedures were retrospectively analyzed. According to the different
      developmental stages of ERCP equipment and techniques, cases were divided into
      four groups. The incidence rates and major risk factors for acute PEP were
      compared between groups. RESULTS: Among the 7,168 cases, the overall incidence of
      PEP was 3.70% (265/7,168). When analyzed against each stage of ERCP development,
      the incidence of PEP was 4.09% (77/1,884) in stage I, 5.79% (86/1,489) in stage
      II, 3.95% (62/1,568) in stage III and 1.80% (40/2,227) in stage IV. By univariate
      analysis, pancreatic stent placement (OR: 0.300) and use of propofol-balanced
      anesthesia (OR: 0.632) seem to be protective factors for acute PEP. By
      multivariate analysis, the following risk factors for PEP could be identified:
      repeated cannulation (OR: 3.462), pancreatic duct injection (OR: 3.218), balloon
      dilation of biliary sphincter (OR: 2.847), papillae precut (OR: 2.493),
      nonselective high-pressure injection (OR: 1.428), excessive electrocoagulation
      incision (OR: 1.263), history of pancreatitis (OR: 3.843) and suspected sphincter
      of Oddi dysfunction (OR: 1.782). CONCLUSIONS: Improved technical procedures were
      associated with a significant reduction in the incidence of PEP. Risks for
      developing PEP may be minimized by constant improvement in ERCP techniques, such
      as routine use of a guidewire, highly selective cannulation, pancreatic stent
      placement and cautious incision.

PMID- 21894058
TI  - A comprehensive classification of invasive procedures for treating the local
      complications of acute pancreatitis based on visualization, route, and purpose.
AB  - BACKGROUND/AIMS: The lack of a system to classify invasive procedures to treat
      local complications of acute pancreatitis is an obstacle to comparing
      interventions. This study aimed to develop and validate a comprehensive
      multidisciplinary classification. METHODS: Standardized terminology was used to
      develop a classification of procedures based on three key components: how the
      lesion is visualized, the route used during the procedure, and the procedure's
      purpose. Gastroenterologists, radiologists, and surgeons (n = 22) from three New
      Zealand centers independently classified 15 published technique descriptions.
      Inter-rater reliability was calculated for each component. The classification's
      clarity, ease of use, and potential to achieve its objectives were rated on a
      Likert scale. RESULTS: The classification's clarity, ease of use, and potential
      to achieve its objectives had median scores of 4/5. Inter-rater reliability for
      visualization, route, and purpose components was substantial at 0.73 (95% CI 0.63
      0.82), 0.79 (95% CI 0.70-0.87), and 0.64 (95% CI 0.53-0.74), respectively.
      CONCLUSIONS: This article describes the development and validation of a
      comprehensive classification for the wide range of procedures used to treat the
      local complications of acute pancreatitis. It has substantial inter-rater
      reliability and high acceptability, which should enhance communication between
      clinicians and facilitate comparison between procedures.

PMID- 21894059
TI  - Prediction of implantable pulse generator longevity in deep brain stimulation:
      limitations and possible solutions in clinical practice.
AB  - BACKGROUND: Deep brain stimulation (DBS) is used in the treatment of movement
      disorders, chronic pain and certain neuropsychiatric conditions. Its effect is
      achieved through local stimulation of specific targets of the brain. Electrical
      pulses are delivered at settings that can be tailored to provide optimum symptom
      control. DBS is powered by an implantable pulse generator (IPG). These IPGs do
      not have an indefinite lifespan and will eventually become depleted. Therefore,
      regular checks are carried out to monitor the IPG's power status. OBJECTIVE: To
      evaluate the utility of computer-based prediction of IPG longevity in patients
      with DBS devices by imputing the device's settings. PATIENTS: Eighty-two IPGs in
      47 consecutive patients were studied comparing the actual longevity of the IPGs
      with their predicted longevity using a computer-based calculator. RESULTS: Our
      study showed that the predicted longevities were too different from actual
      longevities to have a role in clinical practice. The time difference varied by
      more than 12 months in some cases, with a correlation coefficient of <0.68. There
      were multiple reasons for this. CONCLUSION: The longevities of IPGs could not be
      predicted accurately enough for the computer-based calculator to have a role in
      clinical practice or the proactive scheduling of IPG replacement. However,
      rechargeable IPGs may help avoid premature replacements and battery depletions.

PMID- 21894060
TI  - Is a patient controller for Parkinson's disease patients with subthalamic nucleus
      deep brain stimulation reasonable?
AB  - BACKGROUND: A patient controller (PC) is an optional device for patients with
      deep brain stimulation (DBS) to have limited control of their stimulator system.
      OBJECTIVES: We investigated the impact of a PC on DBS safety, most notably the
      handling/prevention of unexpected DBS failure in patients with Parkinson's
      disease (PD). METHODS: PD patients with subthalamic DBS were educated in the use
      of a PC. After a first impulse generator (IPG) replacement, data on the use of
      the PC were obtained from the patients' records and by a patient questionnaire.
      RESULTS: A total of 27 patients with IPG replacements after 4.4 +/- 0.8 years
      (118.8 patient-years) were included. Thirteen patients transiently used the PC to
      optimize stimulation amplitudes. Eighteen patients reported events when they used
      the PC to ensure DBS being on. No accidental switch off by environmental
      electromagnetism was confirmed. In contrast, 4 patients accidentally turned the
      IPG off with the PC. Sixteen patients regularly checked the IPG battery but only
      1 patient noted a low battery status before quarterly control visits. Of the 27
      patients, 26 had anticipated and only 1 an unanticipated IPG replacement.
      CONCLUSIONS: A PC is not needed for patient safety. However, in some patients, a
      PC is helpful to optimize stimulation amplitudes and to increase the patients'
      own perception of safety.

PMID- 21894061
TI  - Abnormal T2-weighted MRI signal surrounding leads in a subset of deep brain
      stimulation patients.
AB  - BACKGROUND: Deep brain stimulation (DBS) surgery is a common treatment option for
      numerous neurological disorders. However, it is not without potential
      complications, such as hemorrhage and infection. Interestingly, we have observed
      several instances of abnormal T2-weighted signal hyperintensity surrounding DBS
      leads on postoperative MRI that are not associated with hemorrhage or infection.
      METHODS: To better characterize the incidence and timing associated with this
      finding, we retrospectively reviewed postoperative imaging for all DBS implants
      performed over 9 years at one institution. RESULTS AND CONCLUSIONS: Fifteen
      instances of T2 signal hyperintensity surrounding DBS leads on postoperative MRI
      scans were observed across 239 implants (6.3% incidence) in 133 patients. The
      signal characteristics were most consistent with vasogenic edema, possibly
      representing an inflammatory response. The finding was typically unilateral, even
      in patients with simultaneous bilateral lead implants. Most affected patients
      were asymptomatic, although 3 were symptomatic and 1 experienced marked gait
      instability that was treated with steroids. T2 signal abnormality was seen more
      commonly in scans obtained 3 or more days after surgery than in those collected
      immediately postoperatively. No differences in age, anatomical target, diagnosis,
      or number of microelectrode passes were noted between patients with or without T2
      signal. Further research will be needed to explain this curious neuroimaging
      finding, and to rule out cause for clinical concern.

PMID- 21894062
TI  - How to improve influenza vaccination rates in the U.S.
AB  - Annual epidemics of seasonal influenza occur during autumn and winter in
      temperate regions and have imposed substantial public health and economic
      burdens. At the global level, these epidemics cause about 3-5 million severe
      cases of illness and about 0.25-0.5 million deaths each year. Although annual
      vaccination is the most effective way to prevent the disease and its severe
      outcomes, influenza vaccination coverage rates have been at suboptimal levels in
      many countries. For instance, the coverage rates among the elderly in 20
      developed nations in 2008 ranged from 21% to 78% (median 65%). In the U.S.,
      influenza vaccination levels among elderly population appeared to reach a
      "plateau" of about 70% after the late 1990s, and levels among child populations
      have remained at less than 50%. In addition, disparities in the coverage rates
      across subpopulations within a country present another important public health
      issue. New approaches are needed for countries striving both to improve their
      overall coverage rates and to eliminate disparities. This review article aims to
      describe a broad conceptual framework of vaccination, and to illustrate four
      potential determinants of influenza vaccination based on empirical analyses of
      U.S. nationally representative populations. These determinants include the
      ongoing influenza epidemic level, mass media reporting on influenza-related
      topics, reimbursement rate for providers to administer influenza vaccination, and
      vaccine supply. It additionally proposes specific policy implications, derived
      from these empirical analyses, to improve the influenza vaccination coverage rate
      and associated disparities in the U.S., which could be generalizable to other
      countries.

PMID- 21894063
TI  - Use of senior center and the health-related quality of life in Korean older
      adults.
AB  - OBJECTIVE: The purpose of the present study was to examine the relationship
      between the use of senior center and health-related quality of life in Korean
      older adults. METHODS: A questionnaire survey was conducted to two types of older
      adults who lived in Busan, Korea: 154 older adults who used a senior center and
      137 older adults who did not use a senior center. The Korean version of short
      form 36-item health survey was administered to assess the health-related quality
      of life. Demographic variables were obtained from a questionnaire. These were
      gender, age, family status, marital status, education, monthly income, present
      illness, body mass index and physical activity. RESULTS: The 8-domain scales of
      physical function and role-physical were significantly higher in the users of the
      senior center compared with the non-users (F=4.87, p=0.027 and F=7.02, p=0.009,
      respectively). The 8-domain scales of vitality was also significantly higher in
      the users of the senior center compared with the non-users (F=7.48, p=0.007).
      CONCLUSIONS: The present study showed that the users of the senior center have
      higher physical function, role-physical and vitality compared with the non-users.
      These findings suggest that although the results are unable to specify causal
      relationships using the senior center may lead to some improvement in health
      related quality of life.

PMID- 21894064
TI  - Intraocular pressure and its determinants in subjects with type 2 diabetes
      mellitus in India.
AB  - OBJECTIVES: This study was conducted to show the intraocular pressure (IOP)
      distribution and the factors affecting IOP in subjects with type 2 diabetes
      mellitus (DM) in India. METHODS: We measured the anthropometric and biochemical
      parameters for confirmed type 2 DM patients. A comprehensive ocular examination
      was performed for 1377 subjects aged > 40 years and residing in Chennai. RESULTS:
      A significant difference in IOP (mean +/- standard deviation) was found between
      men and women (14.6 +/- 2.9 and 15.0 +/- 2.8 mmHg, p = 0.005). A significantly
      elevated IOP was observed among smokers, subjects with systemic hypertension and
      women with clinically significant macular edema (CSME). After a univariate
      analysis, factors associated significantly with higher IOP were elevated systolic
      blood pressure, elevated resting pulse rate and thicker central corneal thickness
      (CCT). In women, elevated glycosylated hemoglobin was associated with a higher
      IOP. After adjusting for all variables, the elevated resting pulse rate and CCT
      were found to be associated with a higher IOP. CONCLUSIONS: Systemic
      hypertension, smoking, pulse rate and CCT were associated with elevated
      intraocular pressure in type 2 DM. Women with type 2 DM, especially those with
      CSME, were more prone to have an elevated IOP.

PMID- 21894065
TI  - Trends in body mass index and associations with physical activity among career
      soldiers in South Korea.
AB  - OBJECTIVE: This study was designed to describe the trends in body mass index
      (BMI) during 6 years (2002 - 2008) and to identify associations between these
      trends and the amount of physical activity of South Korean career soldiers.
      METHOD: This study targeted the 40 993 (38 857 men and 2136 women) of the 58 657
      career soldiers who had undergone four (2002, 2004, 2006, and 2008) biennial
      medical examinations conducted by the National Health Insurance Corporation; 17
      664 soldiers with missing data on height, weight, and physical activity were
      excluded. A linear mixed-regression model was used to categorize changes in BMI
      due to age versus those due to amount of physical activity. RESULTS: Career
      soldiers experienced significant increases in BMI compared with baseline data
      gathered in 2002. The increases in each age group were as follows: men aged 20
      29: 1.16, men aged 30-39: 0.61, men aged 40-49: 0.05, women aged 20-29: 0.35,
      women aged 30-39: 0.30, women aged 40-49: 0.26, and women aged 50-59: 0.21.
      However, men aged 50 or older showed significant decreases (as high as 0.5) in
      BMI compared with baseline data obtained in 2002. They also experienced
      significant decreases in BMI compared with those who reported no physical
      activity. The differences between baseline and final BMIs were: 0.02 for men
      exercising 1-2 times per week, -0.07 for men exercising 3-4 times per week, -0.19
      for men exercising 5-6 times per week, -0.21 for men exercising seven times per
      week, -0.05 for women exercising 1-2 times per week, -0.19 for women exercising 3
      4 times per week, -0.30 for women exercising 5-6 times per week, and -0.30 for
      women exercising seven times per week. CONCLUSIONS: Obesity in South Korean
      career soldiers increased markedly between 2002 and 2008, and our data showed
      that the amount of physical activity was inversely related to increases in BMI.
      Policies to prevent obesity are needed to reduce this trend.

PMID- 21894066
TI  - Trends in cigarette use behaviors among adolescents by region in Korea.
AB  - OBJECTIVES: Understanding recent trends in cigarette smoking among adolescents is
      important in order to develop strategies to prevent cigarette smoking. The aim of
      this study was to compare recent trends in cigarette smoking for adolescents
      living in rural areas, small towns and metropolitan cities in Korea. METHODS: The
      raw data from the Korea Youth Risk Behavior Web-based Survey (KYRBWS) from 2005
      to 2009 were used. Data were analyzed by using the method of complex survey data
      analysis considering complex sampling design. Logistic regression models were
      used to evaluate significant linear time trends in cigarette smoking. The
      indicators of cigarette use behaviors were 'current smoking rate', 'frequent
      smoking rate', 'heavy smoking rate' and 'smoking experience rate before 13 years
      of age'. All analyses were conducted according to gender. RESULTS: Statistically
      significant increasing trends in current smoking rate and frequent smoking rate
      were observed and borderline significant increasing trends in heavy smoking rate
      were shown among rural boys. Among metropolitan city boys, statistically
      significant increasing trends were also seen for frequent smoking. Statistically
      significant decreasing trends in current smoking rate were observed among small
      town and metropolitan city girls. Smoking experience rate before 13 years of age
      for rural girls decreased significantly. CONCLUSIONS: Cigarette smoking
      prevalence among adolescents in the rural areas has increased in the last five
      years especially among boys. Our findings suggest that anti-tobacco program for
      adolescents should be conducted primarily for those in rural areas.

PMID- 21894067
TI  - Fifteen years after the Gozan-Dong glass fiber outbreak, Incheon in 1995.
AB  - OBJECTIVES: In 1995, an outbreak survey in Gozan-dong concluded that an
      association between fiberglass exposure in drinking water and cancer outbreak
      cannot be established. This study follows the subjects from a study in 1995 using
      a data linkage method to examine whether an association existed. The authors will
      address the potential benefits and methodological issues following outbreak
      surveys using data linkage, particularly when informed consent is absent.
      METHODS: This is a follow-up study of 697 (30 exposed) individuals out of the
      original 888 (31 exposed) participants (78.5%) from 1995 to 2007 assessing the
      cancer outcomes and deaths of these individuals. The National Cancer Registry
      (KNCR) and death certificate data were linked using the ID numbers of the
      participants. The standardized incidence ratio (SIR) and standardized mortality
      ratio (SMR) from cancers were calculated by the KNCR. RESULTS: The SIR values for
      all cancer or gastrointestinal cancer (GI) occurrences were the lowest in the
      exposed group (SIR, 0.73; 95% CI, 0.10 to 5.21; 0.00 for GI), while the two
      control groups (control 1: external, control 2: internal) showed slight increases
      in their SIR values (SIR, 1.18 and 1.27 for all cancers; 1.62 and 1.46 for GI).
      All lacked statistical significance. All-cause mortality levels for the three
      groups showed the same pattern (SMR 0.37, 1.29, and 1.11). CONCLUSIONS: This
      study did not refute a finding of non-association with a 13-year follow-up.
      Considering that many outbreak surveys are associated with a small sample size
      and a cross-sectional design, follow-up studies that utilize data linkage should
      become standard procedure.

PMID- 21894068
TI  - [The influence of Donguibogam during the middle Joseon era based on clinical
      records on low back pain in Seungjeongwon ilgi].
AB  - The recently increasing interest in historical records has led to more research
      on historical records in various fields of study. This trend has also affected
      medical research, with the medical climate and popular treatment modalities of
      the past now being revealed based on historical records. However, most research
      on medical history during the Joseon era has been based on the most well-known
      record, Joseon wangjo sillok or Annals of the Joseon Dynasty. Joseon wangjo
      sillok is a comprehensive and organized record of society during the Joseon era
      and contains key knowledge about medical history during the period, but it lacks
      details on the treatment of common disorders at the time. Seungjeongwon ilgi or
      Diary of the Royal Secretariat has detailed records of daily events and is a
      valuable resource for the daily activities of the era. And in the middle Josoen
      era, a variety of medical books - especially Donguibogam - was published.
      Therefore, the authors focused on the under-researched Seungjeongwon ilgi,
      Donguibogam and attempted to assess and evaluate low back pain treatment
      performed on Joseon royalty. The most notable characteristic of low back
      treatment records within the Seungjeongwon ilgi is that diagnosis and treatment
      was made based on an independent Korean medicine, rather than conventional
      Chinese medicine. This paradigm shift is represented in Dongeuibogam, and can be
      seen in the close relationship between Dongeuibogam and national medical exams of
      the day. Along with the pragmatism of the middle Joseon era, medical treatment
      also put more focus on pragmatic treatment methods, and records show emphasis on
      acupuncture and moxibustion and other points in accord with this. The authors
      also observed meaning and limitations of low back pain treatment during that era
      through comparison with current diagnosis and treatment.

PMID- 21894069
TI  - [The introduction of compendium of materia medica and praxis in the late Joseon
      dynasty].
AB  - Sakae Miki said Classified Emergency Materia Medica had been the dominant
      standard of herbology throughout Joseon Dynasty, and that Compendium of Materia
      Medica had only been accepted so lately that a few books used herbological result
      of it in the late Joseon Dynasty. But according to Visiting Old Beijing Diary
      written by Munjoong Seo in 1690, Compendium of Materia Medica was in fact
      introduced before the year 1712, the year Miki Sakae argued to be the year
      Compendium of Materia Medica was accepted to Joseon officially. Now, we can
      assume that the introducing year of Compendium of Materia Medica was faster than
      Miki Sakae's opinion by the following reasons; the effort of Joseon government
      and intellectuals to buy new books of Ming & Ching; the publishing year of the
      book for living in countryside regarded as the first citing literature of
      Compendium of Materia Medica. And the True Records of the Joseon Dynasty and many
      collections written by intellectuals in the 18th century show that the
      herbological knowledge from Compendium of Materia Medica had already spread to
      the corners of Joseon Dynasty. Thus we can make the following assumption:
      Classified Emergency Materia Medica and Compendium of Materia Medica had
      coexisted in the late Joseon Dynasty. Sakae Miki suggested 6 examples which used
      Compendium of Materia Medica in the late Joseon Dynasty. I reviewed two of them
      in this paper, Essentials of Materia Medica & Handbook of Prescriptions from
      Materia Medica. Essentials of Materia Medica quoted Compendium of Materia Medica
      briefly focusing clinical use, and Handbook of Prescriptions from Materia Medica
      also re-compiled Compendium of Materia Medica to practical use according to the
      form of Treasured Mirror of Eastern Medicine. It means that the results of
      Compendium of Materia Medica have been used positively, based on the herbology of
      materia medica from countryside. From this point of view, the hyphothesis there
      weren't any herbological progress after accepting Compendium of Materia Medica in
      the late Joseon Dynasty by Sakae Miki can be denied.

PMID- 21894071
TI  - [White ginseng commercialization and sales expansion activities of Gaesung
      merchants in the 1910s and 1920s].
AB  - Ginseng has always been the typical export item in Korean history. Until the 18th
      century, exporting ginseng was wild ginseng from the mountains. Since the 19th
      century, exporting ginseng became red ginseng, which was red due to steaming and
      drying process. Red ginseng was produced by Gaesung merchants, so that these
      merchants were able to gain the control of the output. Gaesung merchants of the
      19th century exported red ginseng to China and made huge economic success.
      However, when the Korean Empire and Japanese colonial government established red
      ginseng monopoly, it essentially blocked Gaesung traders from manufacturing and
      exporting any further of its prized commodity. Then, the traders turned to sun
      dried white ginseng as a substitute to red ginseng. As a result, white ginseng
      production dramatically increased after 1914, which in turn made Gaesung
      merchants newly aware of the commercial value of white ginseng, which was
      previously ignored. The traders made good use of the traditional medicine herb
      market, which opened annually, to promote the expansion of white ginseng sales.
      Moreover, the merchants also adopted modern marketing techniques, as they founded
      companies to handle solely white ginseng sales, refreshed packaging to raise
      commodity values, and made an effort in advertising and mail order sales. Due to
      such endeavors, demand for white ginseng grew exponentially both in domestic and
      foreign markets, which generated steady growth of white ginseng prices despite
      the rapid increase of its supply. This phenomenon naturally brought about the
      rich economic accomplishments of Gaesung merchants. Through the white ginseng
      sales activities of Gaesung merchants in post-1910s era, two facts can be newly
      uncovered. First, the mass consumption of white ginseng today in Korean society
      took a full-scale step after the 1910s. Second, it was a widely-held view that
      during the Japanese rule, majority of Korean traditional merchants were
      economically ruined, while a small minority collaborated with the colonial
      government to obtain economic success. However, Gaesung merchants in 1910s
      successfully commercialized white ginseng not with the aid of the Japanese but
      with their own efforts alone. Such fact reveals that there were other types of
      traditional merchants during the Japanese colonial period who cannot be explained
      with the common theory.

PMID- 21894070
TI  - [A history of malaria in modern Korea 1876-1945].
AB  - Although it is not certain when malaria began to appear in Korea, malaria is
      believed to have been an endemic disease from ancient times. It was Dr. H. N.
      Allen (1858-1932) who made the first description and diagnosis of malaria in
      terms of Western medicine. In his first year report (1885) of Korean Government
      Hospital he mentioned malaria as the most prevalent disease. Very effective anti
      malarial drug quinine was imported and it made great contribution in treating
      malaria. After Japan had annexed Korea in 1910, policies for public health system
      were fundamentally revised. Japan assumed control of Korean medical institutions
      and built high-quality Western hospitals for the health care of Japanese
      residents. The infectious diseases which were under special surveillance were
      cholera, typhoid fever, dysentery, typhus, scarlet fever, smallpox, and
      paratyphoid fever. Among chronic infectious diseases tuberculosis and leprosy
      were those under special control. Malaria, however, was not one of these
      specially controlled infectious diseases although it was widely spread throughout
      the peninsula. But serious studies on malaria were carried out by Japanese
      medical scientists. In particular, a Japanese parasitologist Kobayasi
      Harujiro(1884-1969) carried out extensive studies on human parasites, including
      malaria, in Korea. According to his study, most of the malaria in Korea turned
      out to be tertian fever. In spite of its high prevalence, malaria did not draw
      much attention from the colonial authorities and no serious measure was taken
      since tertian fever is a mild form of malaria caused by Plasmodium vivax and is
      not so much fatal as tropical malaria caused by P. falciparum. And tertian
      malaria was easily controlled by taking quinine. Although the majority of malaria
      in Korea was tertian fever, other types were not absent. Quartan fever was not
      rarely reported in 1930s. The attitude of colonial authorities toward malaria in
      Korea was contrasted with that in Taiwan. After Japan had set out to colonize
      Taiwan as a result of Sino-Japanese war, malaria in Taiwan was a big obstacle to
      the colonization process. Therefore, a lot of medical scientists were asked to
      engage the malaria research in order to handle health problems in colonized
      countries caused by malaria. Unlike the situation in Taiwan, malaria in Korea did
      not cause a serious health problem as in Taiwan. However, its risk was not
      negligible. In 1933 there were almost 130,000 malaria patients in Korea and 1,800
      patients among them died of malaria. The Japanese Government General took
      measures to control malaria especially during the 1930s and the number of
      patients decreased. However, as Japan engaged in the World War II, the general
      hygienic state of the society worsened and the number of malarial patients
      increased. The worsened situation remains the same after Liberation (1945) and
      during the Korean war (1950-53).

PMID- 21894072
TI  - [Cerebral paragonimiasis and Bo Sung Sim's hemispherectomy in Korea in 1950s
      1960s].
AB  - This paper deals with cerebral paragonimiasis and cerebral hemispherectomy
      conducted as a treatment of cerebral paragonimiasis by Bo Sung Sim in Korea in
      1950s-1960s. He demonstrated that cerebral hemispherectomy could be used for
      unilateral diffuse cerebral paragonimiasis. Sim learned cerebral hemispherectomy
      from Dr. L. A. French. at the University of Minnesota from 1955 to 1957 in
      America. The authors argues that Bo Sung Sim's introduction of cerebral
      hemispherectomy to Korea was not a simple application of an advanced medical
      technology, but a complicated and active process in that Sim used the technique
      to intervene intractable complications from cerebral paragonimiasis such as
      generalized convulsions, spastic hemiplegia and mental deterioration. Bo Sung
      Sim, one of the neurosurgeons of the first generation in Korea, was trained in
      neurology, neuropathology, neuroradiology and animal experiments as well as in
      neurosurgery at the University of Minnesota. After returning to Korea, Sim faced
      parasitic diseases, one of the most serious public health problems at that time,
      which were far different from what he learned in America. As a neurosurgeon, Sim
      tackled with parasitic diseases of the central nervous system with various
      diagnostics and therapeutics. In 1950s, more than one million populations
      suffered from pulmonary paragonimiasis acquired by eating raw crabs or by feeding
      juice of crushed crayfish for the treatment of measles in Korea. About 26.6
      percent of people with paragonimiasis had cerebral paragonimiasis. Before
      bithionol therapy was introduced in 1962, neurosurgery was the only available
      treatment to control increased intracranial pressures, intractable epilepsy,
      paralysis and mental deterioration. Between 1958 to 1962, Bo Sung Sim operated on
      24 patients of cerebral paragonimiasis. In two of them, he performed cerebral
      hemispherectomy to control intractable convulsions when he found diffuse cerebral
      paragonimiasis and cerebral atrophy at the operating table. The two patients were
      recovered dramatically after the operation. The first patient became a part of
      medical campus for 20 years after hemispherectomy, doing chores at the hospital
      and helping Bo Sung Sim for his teaching neuroanatomy. The presence of the
      hemispherectomized patient in the classroom impressed the students deeply.
      Furthermore, the hemispherectomized patient stimulated Sim and his school to
      perform research upon the neuroanatomy and neurophysiology of the brain with
      hemispherectomized animals.

PMID- 21894073
TI  - [Art-chance and art-experience in classical Greece].
AB  - In Classical Greece, works defining the nature of art appeared in the various
      disciplines like medicine, rhetoric, dietetics, architecture and painting.
      Hippocratic authors tried to show that an art of medicine existed indeed. They
      contrasted the concept of art with that of chance, not experience that Plato and
      Aristotle distinguished from art. In fact there are similarities and
      discrepancies between Hippocratic epistemology and Platoic epistemology.
      Hippocratic authors maintained that the products of chance were not captured by
      art. They distinguished the domain of art charactered by explanatory knowledge
      and prediction from the domain of chance ruled by the unexplained and the
      unforeseeable. They minimized the role of luck and believed the role of art.
      Hippocratic authors thought that professional ability contained both knowledge
      and experience. In Hippocratic corpus, experience is a synonym of competence and
      usually has a positive meaning. But Plato gave empirical knowledge the disdainful
      sense and decided a ranking between two types of knowledge. Both Hippocratic
      authors and Plato held that a genuine art had connection with explanatory
      knowledge of the nature of its subject matter. A common theme that goes through
      arguments about art-chance and art-chance is the connection between art and
      nature. Hippocratic authors and Plato regarded art as a highly systematic
      process. Art provides us with general and explanatory knowledge of human nature.
      Art and nature is a mutual relationship. The systematic understanding of nature
      helps us gain the exactness of art and an exact art helps us understand nature
      well.

PMID- 21894074
TI  - "Senility and death of tissues are not a necessary phenomenon": Alexis Carrel and
      the origins of gerontology.
AB  - The French surgeon and Nobel laureate Alexis Carrel's tissue culture has been
      highly influential in biomedicine. This paper contextualizes Carrel's works with
      respect to the birth of gerontology during the first half of the twentieth
      century. I argue that Carrel contributed to gerontology in several respects.
      First, using his "immortal" tissues, he asserted that aging was a contingent
      phenomenon that could be experimentally manipulated. Although this claim was
      eventually challenged, it prompted many scientists to think that aging was not so
      much an unavoidable, unidirectional phenomenon as a process amenable to
      experimental approaches. Second, his research on different culture conditions
      required by distinct cell types encouraged the idea that the rate and mode of
      aging differed in distinct parts of the body. This idea became a basis of later
      gerontologists' claim that each senior person's job in industry should be
      determined according to the degree of senescence shown in his particular body
      parts. It also helped gerontologists make their field a multidisciplinary arena
      that could tackle diverse features of senescence occurring in the body. Third,
      Carrel's public speeches and appearance in popular media encouraged both
      scientists and laypeople to think that research on senescence should be pursued
      more systematically in an era of an increasing elderly population. By analyzing
      the relation of these issues to the efforts to construct gerontology, this paper
      illustrates tissue culture's broader meanings with respect to the emerging
      concerns about the aging population, the need for continued employment of
      seniors, and scientists' hopes for controlling senile processes.

PMID- 21894075
TI  - [Clinical assessment of perioperative course of patients undergoing laparoscopic
      nephrectomy or adrenalectomy without perioperative bowel management].
AB  - Thirty-one patients underwent laparoscopic radical nephrectomy and 27 patients
      underwent laparoscopic adrenalectomy from January, 2005 to September, 2009 by a
      single surgeon authorized by the Japanese Society of Endourology and ESWL. Six
      patients (radical nephrectomy in 3, adrenalectomy in 3) received perioperative
      and 52 patients (radical nephrectomy in 28, adrenalectomy in 24) did not. The
      time of pneumoperitoneum, amount of blood loss, postoperative body temperature
      and complications revealed no obvious problems in the cases without bowel
      management. Perioperative bowel management is commonly applied to the patients,
      but without clinical evidence. Based on the present study, we concluded that
      bowel management may be safely omitted for laparoscopic redical nephrectomy and
      adrenalectomy and it may save medical cost including labor cost.

PMID- 21894076
TI  - [Transurethral lithotripsy with rigid and flexible ureteroscopy for renal and
      ureteral stones: results of the first 100 procedures].
AB  - We evaluated the clinical outcome of transurethral lithotripsy (TUL) using rigid
      & flexible ureteroscopy and holmium : yttrium-aluminum-garnet (YAG) laser in our
      hospital. We retrospectively reviewed 100 consecutive transurethral lithotripsy
      procedures performed on 82 patients from May 2008 to June 2010 at our hospital.
      Twenty-five patients (30%) had multiple stones and 10 patients (12%) had
      bilateral stones. The main stones were located in the renal pelvis, ureteropelvic
      junction, upper ureter, middle ureter, and lower ureter in 14, 12, 26, 3, and 27
      cases, respectively. Median operative time was 75 minutes (range, 18-238
      minutes). Operative complications were 5 cases of pyelonephritis and 1 case of
      ureteral perforation that was managed conservatively with percutaneous
      nephrostomy. The average number of procedures was 1.22 with 65 patients requiring
      one, 16 requiring two, and 1 requiring three procedures. Three patients had shock
      wave lithotripsy (SWL) and two patients had minipercutaneous nephrolithotomy
      (mini-PNL) after first TUL. However, all of these patients eventually needed
      additional TUL. The overall success rate was 99% (81/82). Rigid & flexible
      ureteroscopy and holmium : YAG laser lithotripsy achieved excellent results of
      treatment for urolithiasis. TUL gave a high stone-free rate with low complication
      rates. In Japan, where shock wave lithotripters are widely used, trend of
      treatment for urolithiasis will shift from SWL to TUL.

PMID- 21894077
TI  - [Risk factors for falls and fractures at night in relation to lower urinary tract
      symptoms: a survey of outpatients and inpatients at a general hospital].
AB  - We investigated potential risk factors, including factors related to lower
      urinary tract symptoms (LUTS), for falls and fractures at night among outpatients
      and inpatients in a general hospital, via a questionnaire. The questionnaire
      included items to record the age, sex, number of consulting doctors, history of
      11 particular medical diseases, LUTS, sleep, and falls and fractures at night. We
      distributed the questionnaire to 1,334 patients 51 years old or older in our
      hospital. Of the questionnaires completed, 96.9% were valid for analysis.
      Multivariate analyses revealed that "drinking water before bedtime or while in
      bed" was the strongest risk factor (odds ratio=7.499) for bone fractures while
      "postural syncope" was the strongest risk factor (odds ratio=5.041, except past
      medical history) for falls. In terms of LUTS, urge incontinence was a significant
      risk factor for falls.

PMID- 21894078
TI  - [Analgesic effect of oral tramadol on transrectal ultrasound-guided needle biopsy
      of the prostate in a randomized double-blind study].
AB  - A total of 121 Japanese patients scheduled for prostate biopsy were randomly and
      double-blindly assigned to be given a single oral dose of 100 mg Tramadol mixed
      with 20 ml of sugar syrup or placebo, 30 minutes before the procedure. Pain
      severity was measured by verbal rating scale (VRS) and visual analog scales
      (VAS). We also analyzed cardio-respiratory parameters and complications. Of 121
      patients, 117 replied validly to VRS and VAS ; and 91 of 117 patients replied to
      the cohort questionnaire for analysis of the late disorder, patient's impression,
      prolonged pain and past history of hemorrhoid treatment. Tramadol showed no
      significant effect on pain severity indicated by VRS and VAS, and no change in
      cardiorespiratory parameters. Furthermore, 70 patients without a history of
      hemorrhoid treatment, showed no significant analgesic benefits of Tramadol during
      the biopsy. In total, 3 patients had side effects of vomiting (CTCAE : grade
      1)6), which subsided spontaneously. The oral administration of a single dose of
      100 mg Tramadol 30 minutes before a transrectal needle biopsy of the prostate was
      safe, but was not effective to calm down the pain severity.

PMID- 21894079
TI  - [A case of renal cell carcinoma associated with paraganglioma].
AB  - A 64-year-old man was referred to our hospital for the treatment of left renal
      cell carcinoma associated with a tumor located on the back of the inferior vena
      cava. At first the tumor located on the back of the inferior vena cava was
      suspected to be lymphnode metastasis of renal cell carcinoma. A more detailed
      examination at our hospital revealed elevation of vanillylmandelic acid in urine
      and (131)Imetaiodobenzylguanidine uptake in the tumor. We diagnosed the tumor as
      paraganglioma and operated both tumors at the same time. Histological examination
      revealed chromophobe renal cell carcinoma and paraganglioma. His important to
      discriminate paraganglioma in the renal cell carcinoma that has an atypical
      swelling of lymphnode.

PMID- 21894080
TI  - [Adrenalectomy for metastatic adrenal tumor from uterine leiomyosarcoma: a case
      report].
AB  - A 63-year-female was referred to our department for close examination and
      treatment of a left adrenal tumor found by positron emission tomography and
      computed tomography. She underwent abdominal total hysterectomy and bilateral
      salpingo-oophorectomy for uterine leiomyosarcoma 19 years ago. After the
      operation, she received 2 resections for peritoneal recurrence and 7 resections
      for pulmonary metastases. Magnetic resonance imaging showed a heterogeneous mass
      with a diameter of 7 cm at the left adrenal grand. We carried out open
      adrenalectomy and pathological findings were a metastatic adrenal tumor from
      uterine leiomyosarcoma. No signs of recurrence or metastasis have been observed
      for 6 months after the operation.

PMID- 21894081
TI  - [Localized amyloidosis of the urinary bladder: a case report].
AB  - Amyloidosis is characterized by extracellular deposition of abnormal insoluble
      fibrils, which cause structural and functional disorders. Amyloidosis is
      classified into systemic and localized amyloidosis. Localized amyloidosis in
      individual organs is uncommon. We report a rare case of localized form of primary
      amyloidosis of the urinary bladder. A 76-year-old male visited our hospital with
      a complaint of macroscopic hematuria. Cystoscopy showed submucosal hematoma in
      the anterior wall and broad-based mass occupying the trigone without normal
      mucosa covered by calcification. Transurethral biopsy and resection were
      performed. Histopathological diagnosis was AL type amyloidosis occupying
      submucosal extracellular space. We gave the patient occlusive dressing with
      dimethyl sulfoxide. In 12 months, cystoscopy and magnetic resonance imaging
      revealed improvement of the mass-like lesion in the bladder wall.

PMID- 21894082
TI  - [A case of primary malignant lymphoma of the prostate].
AB  - A 79-year-old man presented with a chief complaint of difficulty in urination.
      Digital rectal examination and transrectal ultrasonography showed an enlarged
      prostate. Holmium laser enucleation of the prostate (HoLEP) was performed.
      Histological findings revealed diffuse large B-cell lymphoma by
      immunohistochemical studies. Pelvic Lymph nodes were swollen on fluoro
      deoxygiucose-positron emission tomography examination. Therefore, the disease was
      classified into clinical stage II according to Ann Arbor's criteria. The patient
      achieved complete response after 6 cycles of combination chemotherapy with
      rituximab, pirarubicin, cyclophosphamide, vincristine, and prednisolone (R-THP
      COP). Now, 1 year 8 months after the chemotherapy, he remains free of the
      disease.

PMID- 21894083
TI  - [Metachronous bilateral testicular tumors in a case of male infertility].
AB  - A 42-year-old man referred to our hospital with the chief complaint of a solid
      mass of right scrotal contents. As ultrasonography revealed a right testicular
      tumor, right high orchiectomy was performed and the pathlogical diagnosis was
      testicular seminoma. At the age of 35-year-old, he was admitted to another
      hospital for male infertility due to azoospermia. Because left testicular tumor
      was found, left high orchiectomy was performed, with right testicular biopsy and
      testicular sperm extraction of the right testis at the same time. Pathological
      diagnosis revealed left testicular seminoma and no malignancy of the right
      testicular biopsy specimen. After the second operation, he has been receiving
      androgen replacement therapy, with no evidence of tumor recurrence.

PMID- 21894084
TI  - [Testicular mature teratoma with onset during childhood and removed 40 years
      later: a case report].
AB  - A 56-year-old man presented with a painless mass in the left scrotum. The mass
      was first noticed when he was a junior high school student,and it had been left
      for about 40 years. The intrascrotal tumor of 7 cm in diameter was elastic soft
      and smooth. The serum levels of alpha -fetoprotein, beta -human chorionic
      gonadotropin and lactate dehydrogenase were within each individual normal range.
      He was diagnosed as having a left testicular tumor (cT1N0M0) and underwent left
      high orchiectomy. Histopathological diagnosis was mature teratoma without any
      malignant germ cell components. No evidence of recurrence has been observed for 4
      years after the operation.

PMID- 21894085
TI  - [Brain tumor (germinoma) diagnosed after assessment for male late-onset
      hypogonadism syndrome: a case report].
AB  - A 44-year-old man suffered from sleep disturbance, headache, lack of energy and
      appetite loss. His local doctor recommended he consult our clinic for further
      examination of late-onset hypogonadism. His aging males' symptoms (AMS) and
      international index of erectile function (IIEF-5) scores were 62 and 1,
      respectively. His biochemistry revealed 0.29 mIU/ml luteinizing hormone (LH),
      1.36 mIU/ml follicular stimulating hormone (FSH), 0.16 ng/ml total testosterone
      (TT) and<0.6 pg/ml free testosterone (FT). Male hypogonadotropic hypogonadism was
      suspected from these results, He was then referred to a neurosurgeon for
      discrimination of intracranial disease where magnetic resonance imaging (MRI)
      revealed multiple intracranial tumors. An open brain biopsy was performed, and
      germinoma was diagnosed. After 4 courses of anti-cancer chemotherapy, complete
      remission was achieved. He was followed up endocrinologically by administration
      of testosterone injections along with other endocrinology replacement treatments.
      However, MRI 3 months later revealed tumor recurrence in the left lateral
      ventricle, and he has been receiving radiation therapy.

PMID- 21894086
TI  - Antioxidant, anti-lipoxygenase and cytotoxic activity of Leptadenia pyrotechnica
      (Forssk.) decne polyphenolic constituents.
AB  - Leptadenia pyrotechnica Forssk is a traditional medicinal herb used for treatment
      of inflammatory diseases and cancer. In this research, the aqueous ethanolic
      crude extract of Leptadenia pyrotechnica aerial parts, along with its ethyl
      acetate, n-butanol and water partitioning fractions were evaluated for their
      antioxidant capacity, polyphenolic content, anti-inflammatory and anti-cancer
      properties. The total antioxidant capacity was estimated by the FRAP, DPPH, ABTS
      and beta-carotene bleaching assays.The ethyl acetate fraction exhibited the
      highest polyphenolic content (252.27 mg gallic acid/g) and the best antioxidant
      activity (1.2, 0.57, 0.45 mmol ascorbic acid equivalent/g in the FRAP, ABTS and
      DPPH assays, respectively). Furthermore, the same extract showed appreciable anti
      inflammatory via lipoxygenase (LOX) inhibitory activity (IC50 = 1.41 ug/mL).
      Moreover, the ethyl acetate fraction also showed the strongest cytotoxic effect
      (IC50 = 43.16 ug/mL) against MCF-7 human breast cancer cell line. These results
      suggest that this plant may be considered an interesting source of compounds with
      antioxidant, anti-inflammatory and anti-cancer properties for therapeutic,
      nutraceutical and functional food applications.

PMID- 21894087
TI  - Recent advances in microflow photochemistry.
AB  - This review summarizes recent advances in microflow photochemical technologies
      and transformations. The portfolio of reactions comprises homogeneous and
      heterogeneous types, among them photoadditions, photorearrangements,
      photoreductions, photodecarboxylations, photooxygenations and photochlorinations.
      While microflow photochemistry is most commonly employed as a micro-scale
      synthesis tool, scale-up and technical production processes have already been
      developed.

PMID- 21894088
TI  - Synthesis and SAR study of novel peptide aldehydes as inhibitors of 20S
      proteasome.
AB  - Based on the analysis of the crystal structure of MG101 (1) and 20S proteasomes,
      a new series of peptide aldehyde derivatives were designed and synthesized. Their
      ability to inhibit 20S proteasome was assayed. Among them, Cbz-Glu(OtBu)-Phe
      Leucinal (3c), Cbz-Glu(OtBu)-Leu-Leucinal (3d), and Boc-Ser(OBzl)-Leu-Leucinal
      (3o) exhibited the most activity, which represented an order of magnitude
      enhancement compared with MG132 (2). The covalent docking protocol was used to
      explore the binding mode. The structure-activity relationship of the peptide
      aldehyde inhibitors is discussed.

PMID- 21894089
TI  - 1,3-substituted imidazolidine-2,4,5-triones: synthesis and inhibition of
      cholinergic enzymes.
AB  - A series of novel and highly active acetylcholinesterase and
      butyrylcholinesterase inhibitors derived from substituted benzothiazoles
      containing an imidazolidine-2,4,5-trione moiety were synthesized and
      characterized. The molecular structure of 1-(2,6-diisopropyl-phenyl)-3-[(1R)-1-(6
      fluoro-1,3-benzothiazol-2-yl)ethyl]-imidazolidine-2,4,5-trione (3g) was
      determined by single-crystal X-ray diffraction. Both optical isomers are present
      as two independent molecules in the triclinic crystal system. The lipophilicity
      of the compounds was determined as the partition coefficient log K(ow) using the
      traditional shake-flask method. The in vitro inhibitory activity on
      acetylcholinesterase from electric eel and butyrylcholinesterase isolated from
      equine serum was determined. The inhibitory activity on acetylcholinesterase was
      significantly higher than that of the standard drug rivastigmine. The discussed
      compounds are also promising inhibitors of butyrylcholinesterase, as some of the
      prepared compounds inhibit butyrylcholinesterase better than the internal
      standards rivastigmine and galanthamine. The highest inhibitory activity (IC50 =
      1.66 MUmol/L) corresponds to the compound 1-(4-isopropylphenyl)-3-[(R)-1-(6
      fluorobenzo[d]thiazol-2-yl)ethyl]imidazolidine-2,4,5-trione (3d). For all the
      studied compounds, the relationships between the lipophilicity and the chemical
      structure as well as their structure-activity relationships are discussed.

PMID- 21894091
TI  - Editorial: on neuroscience, epidemiology, pharmacotherapy, recovery, treatment
      resistance, and community mental health teams.

PMID- 21894090
TI  - Bioassay-directed isolation of active compounds with antiyeast activity from a
      Cassia fistula seed extract.
AB  - BACKGROUND AND OBJECTIVE: Cassia fistula L belongs to the family Leguminosae, and
      it is one of the most popular herbal products in tropical countries. C. fistula
      seeds have been used as a herbal medicine and have pharmacological activity which
      includes anti-bacterial, anti-fungal, and antioxidant properties. The goal of
      this study was to identify compounds from C. fistula seeds which are responsible
      for anti-Candida albicans activity using bioassay-directed isolation. RESULTS:
      The preliminary phytochemical screening of the plant seed revealed the presence
      of anthraquinones, flavonoids, saponins, tannins and terpenoids. The isolation of
      active compounds was carried out in four steps: multiple extractions,
      fractionation using column chromatography and purification using preparative thin
      layer chromatography (TLC) and liquid chromatography/mass spectrometry (LC/MS).
      The structure of separated compounds was determined on the basis of mass
      spectrometry data. One compound was identified is roseanone. CONCLUSIONS: The MS
      analysis on the active fraction from seed extract of C. fistula confirmed the
      presence of roseanone with antiyeast activity.

PMID- 21894092
TI  - Predictability of levels of physical and mental health: a 2 year longitudinal
      study.
AB  - OBJECTIVE: To identify the social, family, personality traits and health locus of
      control factors which influence physical and mental health, consumption of
      medications, and frequency of medical consultations. SUBJECTS AND METHODS: Twenty
      participants were included in a two years long longitudinal study. At baseline,
      the participants' age, gender, family composition, net income, chronic
      treatments, family dynamics (Family Adaptation and Cohesion Scale),
      Multidimensional Health Locus of Control, and personality (NEO Personality
      Inventory) were recorded. Every six months their state of mental and physical
      health (12 Survey Factors and Hamilton Depression Scale), consumption of
      medications, and number of medical consultations were reassessed. RESULTS:
      Regarding mental, and physical health, and scores on the Hamilton Depression
      Scale we can explain 50% of the variance, of which 25% accounts for age or for
      the number of persons living together, 15% accounts for the cohesion of the
      actual couple or nuclear family and 10% on account for neuroticism or on the
      Internal HLC. With regard to the number of medications and consultations only 30%
      of the variance is accounted for: 10% for gender, 10% for the cohesion of the
      ideal family and 10% for neuroticism or extraversion. CONCLUSION: These results
      can obviously be used in the field of secondary prevention, for example in
      raising GPs' awareness to the typical profile of patients who are at risk of
      mental or physical health problems. Ideally these results should also serve for
      primary prevention, but how can we influence demographic variables, family
      cohesion or personality?

PMID- 21894093
TI  - Are somatisation symptoms important evidence for an early diagnosis of bipolar
      spectrum mood disorders?
AB  - Four-hundred and twenty three consecutive patients who have been seen in a
      private psychiatric clinic were assessed for bipolar disorder. A large proportion
      of these patients were found to demonstrate a number of somatic syndromes. The
      main somatic syndromes found on the patients' "first visit" have been: colitis
      (45% of the patients), gastritis (25%), migraine (8%) others (above all with
      dermatological symptoms: 2%). All the patients presented muscular tension at
      their "first visit". Somatic syndromes constitute an important pointer for the
      diagnosis of bipolar spectrum disorders.

PMID- 21894094
TI  - Management of marked liver enzyme increase during olanzapine treatment: a case
      report and review of the literature.
AB  - OBJECTIVES: Atypical antipsychotics commonly cause isolated asymptomatic increase
      in the aminotransferase levels. Furthermore, the strategy in the choice of
      antipsychotic agent must take into account hepatic tolerance because of the non
      negligible incidence of liver disorders among the psychiatric population. The aim
      of this article is to better understand the strategy to adopt during an increase
      of liver enzymes in a psychotic patient under atypical neuroleptic treatment.
      METHOD: A clinical case is presented of a female patient treated for psychotic
      decompensation with increase of liver enzymes (Olanzapine). Her treatment was
      changed several times over a period of 7 years and laboratory investigations were
      conducted simultaneously. RESULTS: It seems that the increase of liver enzymes is
      slightly more frequent with Clozapine and Olanzapine than Risperidone, Perazine
      and Haloperiol. CONCLUSION: The different mechanisms of hepatotoxicity are
      unknown at present but it seems that the hypersensibility mechanism is likely to
      be dose dependent. During an increase of enzymes, it is important to combine a
      control of hepatic enzymes with a reduction of neuroleptic dosage.
      Discontinuation should be considered if a continued increase of enzymes above
      certain values is shown or if a clinical symptom appears. We note also that some
      risk factors were found, including geriatric or pedopsychiatric age, obesity, and
      association with active ingredients or addictive substances responsible for
      hepatic disorders.

PMID- 21894095
TI  - Effect of tianeptine on cognitive functions in patients with depressive disorders
      during a 3-month observation.
AB  - OBJECTIVE: The authors put forward the hypotheses that during a three-month
      treatment with tianeptine in patients with depressive disorders there is an
      improvement in the short-term memory, reaction time and attention. SUBJECT AND
      METHODS: 20 patients suffering from depression, were included in the study.
      During the entire research period all patients were treated with monotherapy with
      tianeptine. Cognitive function measurements were performed using the Vienna Test
      System. RESULTS: Our study showed an improvement in the all the assessed
      functions: patients treated with tianeptine had better performance in tests
      measuring short term memory and learning processes as well as reaction time and
      attention. CONCLUSION: In conclusion, the study shows that tianeptine improves
      cognitive functions in depressed patients.

PMID- 21894096
TI  - Prevalence of co-morbid bipolar disorder and migraine in a regional hospital
      psychiatric outpatient department.
AB  - Current literature suggests patients with bipolar disorder are at increased risk
      of developing migraine compared with the general population and patients with
      other affective disorders. This study examined whether this finding was evident
      in the outpatient department of a regional psychiatric hospital. Using a patient
      database (n=1083), records were screened for bipolar disorder (n=169) or self
      report of migraine (n=46). 8 cases of co-morbid migraine and bipolar disorder
      were revealed (4.7% prevalence). This and the general prevalence of migraine
      (4.2%) are substantially lower than previously reported. Reasons for and
      implications of this finding are discussed.

PMID- 21894097
TI  - Mixed affective states: a study within a community mental health team with
      treatment recommendations.
AB  - INTRODUCTION: Agitated Depression and Bipolar mixed states combine depressive and
      manic symptoms, reflecting severe forms of affective disorders with an increased
      suicide risk. These states have not been defined with adequate consensus and
      hence present a diagnostic and therapeutic challenge. In this study, we argue
      that both states are part of the bipolar spectrum rather than a distinct
      affective syndrome or a mixed anxiety-depression state. METHODS: The current
      literature has been reviewed and suggestions are made for a unified definition of
      this entity, which would be valuable in recognising this dangerous state. We have
      then studied 17 cases of mixed states identified from a database held by a UK
      community mental health team. We have studied the treatments offered and
      estimated the time these treatments have taken to end the mixed state and so
      reduce the risk of suicide. RESULTS: Not surprisingly, there are no clear
      recommendations for treatment of these mixed states. We found that The best
      results were achieved with a three pronged regimen including increasing/adding
      mood stabilisers; and/or increasing/adding antipsychotics; as well as decreasing
      antidepressants. Resolution was achieved in two and a half weeks. DISCUSSION:
      From this work we have deduced several general principles, which are here
      reviewed and hence we have been able to suggest possible treatment strategies.
      CONCLUSION: Because of the close link between affective mixed states and
      suicidality, it is of great importance that patients be brought out of the mixed
      affective state as soon as possible, hence we believe that our findings are of
      importance in managing these patients. However we recommend further study on a
      larger sample in order to confirm our findings.

PMID- 21894098
TI  - Trends of admissions of conversion disorder in Mosul Iraq.
AB  - AIMS: Our study aims to make inferences from inpatient admission of conversion
      disorder with regards it's age and sex distribution, clinical presentation,
      yearly distribution of admission and morbidity of conversion disorder in
      comparison to total psychiatric admissions. It also compares it's results with
      those of previous studies in this country, neighbouring countries and western
      studies. METHODS: A case notes review was done for admissions of this disorder
      for five years in Mosul University Hospital. The data were inputted into SPSS
      programme and analysed. The statistical analysis was by t-test, Anova and
      regression. RESULTS: Two hundred seventy five patients were admitted during the
      period; 224 women and 51 men. The majority of men came from Urban areas compared
      to 58% of women. Single status was over represented; 59% compared to 34% married.
      Women formed 82% of the singles, 90% of the widows and 83% of the divorced.
      Pseudo-fits was the most frequent diagnosis. There was no significant change in
      the number of yearly admissions apart from the first year. The proportion of
      conversion disorders compared to total psychiatric disorders admissions was 7.4%.
      IMPLICATIONS: Results were consistent with national studies but showed higher
      figures than neighbouring countries. What was interesting was that, results were
      consistent with figures in United Kingdom before 1950.

PMID- 21894099
TI  - Unusual presentation of a patient with GBL withdrawal: a case report.
AB  - GBL (gamma-butyro-lactone) is converted to Gamma hydroxyl butyrate (GHB) in the
      body. GBL and GHB are available in liquid form and powder form. Once categorised
      under "legal highs", these two are not associated with any dependence or
      withdrawal in animal studies. But there are case reports indicating their high
      dependence potential in humans. We here present a case of a 29 year old who came
      to the attention of psychiatric services with very bizarre presentation and
      needed a host of investigations and expert views from various medical
      disciplines. He was treated mainly symptomatically followed by a sudden dramatic
      recovery on the 11th day after presentation. GBL is getting popular as a
      recreational drug and its withdrawal should be seriously considered in the list
      of medical causes leading to Delirium.

PMID- 21894100
TI  - Citalopram may reduce sympathoadrenal hyperactivity in elderly depressed
      patients: an open multicenter study in Belgium and Luxembourg.
AB  - INTRODUCTION: Through effects of catecholamines upon the heart, blood vessels and
      platelets, sympathoadrenal hyperactivity contributes to the development of
      cardiovascular diseases in elderly depressed patients. To assess the
      cardiovascular effect of Citalopram in elderly depressed patients, data from an
      open multicenter study in Belgium and Luxembourg, in which a total of 811
      patients were evaluated, was retrospectively analysed. Although the aim of the
      study was to assess the efficacy and safety of Citalopram, blood pressure and
      heart rate were also monitored. SUBJECT AND METHODS: Patients included in the
      study were referred either by psychiatrists, geriatricians or general
      practitioners. Clinical assessment included ratings on the Hamilton Rating
      Depression Scale, the Clinical Global Impression Scale, the UKU Side effect
      rating scale and the assessment of side effects spontaneously reported. RESULTS:
      With few side effects, Citalopram significantly improves the clinical condition
      of elderly patients suffering from depressive symptoms. A series of repeated
      multivariate analyses of covariance were performed on heart rate and blood
      pressure controlling for the effect of age. Interestingly, a sustained decrease
      of these parameters was shown during the whole study period reaching significance
      for systolic blood pressure (p<0.05). These effects were observed both in
      responding as well as non-responding patients, and were somewhat more marked in
      responders for heart rate (p=0.058). CONCLUSION: The slight but significant
      decrease in systolic blood pressure and heart rate suggests that citalopram may
      reduce sympathoadrenal hyperactivity and the related increased cardiovascular
      morbidity and mortality associated with depression.

PMID- 21894101
TI  - Neuroleptic Malignant syndrome (NMS): a rare presentation induced by an
      antiemetic - case report.
AB  - Neuroleptic Malignant Syndrome is one of the life threatening complications of
      antipsychotic psychotropic medication. We here report a case of a 39 years old
      male who has had a diagnosis of paranoid schizophrenia since the age of 18. He
      had been on antipsychotic therapy since then. He was stable on a combination of
      antipsychotics. He had mild hyper-salivation for a long time but was not very
      concerned about it. He requested and was prescribed Hyoscine Hydrobromide 300 mcg
      BD for hyper-salivation. There was no other medication change. After 5 days of
      starting Kwells, the patient presented with Neuroleptic Malignant syndrome. One
      has to watch for NMS while starting Hyoscine Hydrbromide for someone on
      antispychotics.

PMID- 21894102
TI  - The way young people see the mentally ill: a questionnaire study.
AB  - BACKGROUND: The stigmatizing of the mentally ill is quite common and has numerous
      social and economical consequences for these individuals. SUBJECTS AND METHODS:
      The aim of this paper was to examine young peoples' beliefs regarding the
      mentally disordered. The authors' questionnaire regarding the interviewees' age,
      gender, social background and their opinions on the mentally ill was conducted
      among a popular portal's users. RESULTS: 11900 people were questioned, including
      71% women. 30% of the interviewees were under the age of 19, while 34% of them
      were between 19 and 24 years old and 36% were over 24. 39% of the interviewees
      stated they closely knew at least one mentally ill person. 44% of the questioned
      believed a lot of criminal offenders were mentally ill. 66% of interviewees would
      not mind sharing a flat with a mentally disordered person, 64% would agree to
      work with one. Those who personally knew a mentally disordered person were more
      inclined to share a flat or start a relationship with such an individual, than
      the rest of the interviewed (51% vs. 37% for flat sharing and 38% vs. 26% for
      starting a relationship, p<0.001). More questioned under the age of 19 believed
      that significant number of criminal offenders were mentally ill, than those over
      the age of 24 (50% vs. 37%, p<0.001). CONCLUSIONS: According to the acquired
      data, many young Poles believe that the mentally disordered are inclined to break
      the law and behave aggressively. These opinions seem to be related amongst others
      to age and gender, and they result in unwillingness to have relations with the
      mentally disordered.

PMID- 21894103
TI  - POMHS 9b - antipsychotic prescribing in people with a learning disability.
AB  - INTRODUCTION: Prescribing Observatory for Mental Health (POMH-UK) runs national
      audit-based quality improvement programmes open to all specialist mental health
      services in the UK to help improve prescribing practice in discrete areas. AIMS:
      The baseline sample and this re-audit represent the largest audits of
      antipsychotic prescribing in PWLD that have been conducted to date; and thus
      provide the most generalisable picture of such prescribing nationally.
      METHODOLOGY: A case note audit of use of antipsychotic medication in PWLD was
      conducted using standard data collection tool provided by POMH-UK. Trust wide, 7
      clinical teams in Essex and Bedfordshire & Luton, participated in the re-audit.
      Analysis and benchmarking was conducted centrally by POMH-UK and an
      individualised Trust report was compiled by POMH-UK for local review and
      consideration. STANDARDS: The indication for treatment with antipsychotic
      medication should be documented in the clinical records (Deb 2006). The
      continuing need for antipsychotic medication should be reviewed at least once a
      year (Deb 2006). Side effects of antipsychotic medication should be reviewed at
      least once a year. This review should include assessment for the presence of
      extrapyramidal side effects (EPS), and screening for the 4 aspects of the
      metabolic syndrome: obesity, hypertension, impaired glucose tolerance and
      dyslipidaemia (NICE schizophrenia guideline update CG82, 2009). FINDINGS: Out of
      three standards measured, Standard One maintained 100% throughout the baseline
      and re-audit and Standard Two achieved over 90% throughout baseline and re-audit.
      Standard 3 has improved from baseline to re-audit. Overall, there has been clear
      improvement in all 3 standards from baseline audit.

PMID- 21894104
TI  - Re-audit of physical examination on admission.
AB  - Re-audit of the physical examination of older adults admitted to one of two
      inpatient Older Adult wards at the Maudsley Hospital found that on admission,
      only 58% of patients had a brief physical examination and 43% had a full physical
      examination, and after 72 hours only 65% had a full physical examination. This is
      a slight improvement on the previous audit but still falls short of the target of
      90% of patients having a full physical examination within 72 hours of admission.
      Recommendations include education of junior and senior doctors of the need for
      physical examination via presentation of audit and distribution of results,
      consideration of the use of a proforma to gather information on physical
      examination which may have been done in an acute hospital and a further re-audit
      to see if outcomes have improved.

PMID- 21894105
TI  - Review: bipolar disorder and poetic genius.
AB  - INTRODUCTION: "We of the craft (poets) are all crazy," remarked the 18th century
      British romanticist Lord Byron (George Gordon) about himself and his fellow
      poets. Implied in this statement is the notion that there exists a special kind
      of relationship between poets and being "crazy". A relationship between
      psychopathology and the artistic temperament is one of the oldest and most
      persistent of cultural notions; it is also one of the most contentious and
      controversial. The purpose of this exposition is to investigate if a correlation
      between bipolar disorder and poetic genius really does exist. METHODS: A
      literature search was conducted along with a review of Professor Jamison's
      treatise Touched with Fire: Manic Depressive Illness and the Artistic
      Temperament. A detailed case study of Lord Byron was also performed in order to
      gain a qualitative insight into the psyche of a notorious poet who was alleged to
      suffer from bipolar disorder. RESULTS: Recent research employing systematic and
      biographical methodology has given strong support to a much higher rate of mood
      disorders in artistic populations than could be expected from chance alone. A
      British study spearheaded by Professor Jamison on living writers and artists
      revealed many overlapping mood, cognitive, and behavioral changes between
      hypomania and intense creative states. In the case of Lord Byron, the clinical
      hallmark of manic-depressive illness is its recurrent, episodic nature, which
      Byron had in an almost textbook manner. Byron also had a family history
      remarkable for its suicide in itself more likely to be associated with bipolar
      disorder than with any other condition. DISCUSSION: Not all writers and artists
      suffer from major mood disorders. Likewise, most people who have a major mood
      disorder are not writers or artists. It seems counterintuitive that melancholy
      could be associated with artistic inspiration and productivity; the milder manic
      states would seem, at first thought, to be more obviously linked. In the case of
      Lord Byron, his temperament made him exquisitely responsive to virtually
      everything in his physical and psychological world; it gave him much of his great
      capacity for passion and understanding, as well as for suffering thus giving
      credence to the notion that there exists a correlation between bipolar disorder
      and poetic genius.

PMID- 21894106
TI  - OpenMinds: creating a mental health workshop for teenagers to tackle stigma and
      raise awareness.
AB  - As a group of four clinical medical students from Cambridge University, we
      undertook a Student Selected Module (SSC- "OpenMinds") whereby we designed and
      delivered a workshop about mental health to year 9 pupils. The aim of our SSC was
      to produce an interactive, informative lesson which addressed the complex issues
      of stigma and discrimination against those suffering from a mental illness as
      well as teaching the pupils how to recognise mental health problems and provide
      them with guidance on how to seek help. We split a fifty minute session into the
      following sections: tackling stigma; how common mental illness is; celebrity
      examples; real life examples; role play; and small group work. To engage the
      pupils we used a combination of teaching modalities targeting all learning. We
      delivered the workshop to four separate classes and received feedback from the
      pupils after each. We used this feedback to adapt and improve our presentation
      and assess the efficacy. Feedback was overwhelmingly positive with the striking
      results of 101/109 pupils saying that they would recommend the workshop to a
      friend and 68/109 pupils saying they enjoyed all aspects. Our SSC built upon work
      by a contingent of trainee Psychiatrists who undertook a similar project of
      mental health education for teenagers, called "Heads above the rest", in Northern
      Ireland with great success. By continuing their work we were able to demonstrate
      that medical students can successfully complete the same project under the
      guidance of a Psychiatrist, thus increasing the sustainability of the project by
      reducing the time burden on the Psychiatrists. Participating in the project was
      also valuable to our own personal development of teaching skills.

PMID- 21894107
TI  - Depression management - from neurobiology to a shared care approach.
AB  - The management of depression has recently been the focus of several articles, in
      particular regarding the efficacy of pharmacological and other treatments. In
      order for these to be effective as possible, correct diagnosis, consideration of
      the underlying neurobiology and an appropriate provision of healthcare services
      must be ensured.

PMID- 21894108
TI  - Differences between training GPs to manage depression in primary care and issuing
      them with guidelines, and a system of collaborative care in the treatment of
      depression between primary and secondary care.
AB  - Here we describe the differences and similarities between training General
      Practitioners (GPs) to manage depression in primary care and issuing them with
      guidelines, and a system of Collaborative care in the treatment of depression
      between primary and secondary care. From these we deduce the reasons why
      collaborative care may offer better treatment outcomes than the issuing of
      guidelines to GPs.

PMID- 21894109
TI  - Impact of olanzapine on cognitive functions in patients with schizophrenia during
      an observation period of six months.
AB  - OBJECTIVE: The objective of our study was to evaluate the effect of olanzapine
      treatment on selected cognitive functions in patients suffering from
      schizophrenia during an observation period of six-months. SUBJECTS AND METHODS:
      Twenty patients with a diagnosis of schizophrenia according to ICD-10 criteria
      for research were examined. One day before initiation of olanzapine a baseline
      assessment was performed. The neuropsychological examination was repeated 28
      days, 60 days, 3 months, and 6 months after the beginning of treatment. Cognitive
      function measurements were performed using Signal, COGNITRON and RT tests, being
      a part of the computer-based Vienna Test System (VTS). RESULTS: Our study showed
      an improvement in the assessed cognitive functions. Impairments in cognitive
      domains were observed at baseline as compared to published normative data, and
      enhancement in achieved results was observed subsequently in all stages of the
      treatment until the 6th month. CONCLUSION: The above results are consistent with
      a number of other studies on the impact on cognitive functioning in patients with
      schizophrenia treated with olanzapine.

PMID- 21894110
TI  - Depression or depressiveness in patients diagnosed with Anorexia Nervosa and
      Bulimia Nervosa - pilot research.
AB  - OBJECTIVES: The target of this work is to consider if depressive symptoms
      intercurrent with patients suffering from Anorexia Nervosa (AN) and Bulimia
      Nervosa (BN) form a depression complex or whether they are physiological
      depression accompanying adolescence. We wished to observe the perception of these
      patients,of their functioning, both social and within their families and also
      looking for common point in the issues mentioned above trying to locate them
      within the course of the basic illness. SUBJECTS AND METHODS: We studied 19
      patients suffering from eating disorders, and aged between 12 and 24 years old.
      15 of them suffered from the restrictive form of AN and 4 suffered from BN. The
      control group consisted of 30 healthy girls in the same age interval. In the
      study authors used the Beck Depression Inventory (BDI) and the Quebec Quality of
      Life Questionnaire. RESULTS: Comparison of a number of points acquired in the
      survey using Beck Depression Scale revealed statistic significance at the level
      p<0.001 which points to a more frequent occurrence of depression symptoms among
      persons with eating disorders comparing to control group. The survey using the
      Questionnaire for Social Quality showed no statistically significant differences
      between study and control groups (p>0.05). The authors observed a statistically
      significant increased frequency of suicidal thoughts in the study group compared
      to the controls. CONCLUSIONS: To diagnose depression, depressive symptoms
      presented by the patients must give the image of depression at the clinical
      level. The result of the Beck's scale needs to be confronted with the clinical
      picture. Depression in adolescence requires differentiation from depressiveness.

PMID- 21894111
TI  - Gene environment interactions in bipolar disorder.
AB  - It has been estimated that the heritable component of bipolar disorder ranges
      between 80 and 90%. However, even genome-wide association studies explain only a
      fraction of phenotypic variability not resolving the problem of "lost
      heritability". Although direct evidence for epigenetic dysfunction in bipolar
      disorder is still limited, methodological technologies in epigenomic profiling
      have advanced, offering even single cell analysing and resolving the problem of
      cell heterogeneity in epigenetics research. Gene overlapping with other mental
      disorders represents another problem in identifying potential susceptibility
      genes in bipolar disorder. Better understanding of the interplay between multiple
      environmental and genetic factors involved in the patogenesis of bipolar disorder
      could provide relevant information for treatment of patients with this complex
      disorder. Future studies on the role of these factors in psychopathological
      conditions, subphenotypes and endophenotypes may greatly benefit by using more
      precise clinical data and a combined approach with multiple research tools
      incorporated into a single study.

PMID- 21894112
TI  - 'Something has changed'. Developing early intervention in service in Trieste.
AB  - The purpose of this project is to optimize early detection and early intervention
      in psychosis, in adolescents and young adults. The goal is to reduce DUP
      (Duration of Untreated Psychosis) through the integrated work of trans
      disciplinary teams and youth-friendly (health and social) services. This should
      lead to a reduction of stigma and an improved accessibility to appropriate care.
      The aim we wish to achieve is a reduction of the incidence and prevalence of
      psychosis in the area covered by the Department of Mental Health of Trieste.

PMID- 21894113
TI  - Compliance with ECT NICE guidance by the John Connolly ECT clinic: January 2010 -
      July 2010.
AB  - OBJECTIVES: To review current practice at the John Connolly Wing ECT clinic and
      to explore compliance with NICE ECT guidance. Standards used included the ECT
      TA59 guidelines of 2003 with the updated depression guidance CG90 of 2009. To
      recommend a programme of action to the Trust which would ensure that clinical
      practice and service delivery within the Trust complies with NICE guidance.
      METHOD: A retrospective baseline Trust wide audit was conducted between the
      period of January 2010 to July 2010 inclusive. Cases were identified using ECT
      clinic record then computer Rio notes explored for evidence of compliance with
      NICE guidelines as set out in the audit standards. All data was extracted from
      the case notes on the Rio system. An audit tool was completed for each case. The
      data recorded on the audit tool was explored and entered onto an Excel
      spreadsheet for analysis. RESULTS: A total of 14 patients were identified. Of
      these, 6 were male and 8 were female. They comprised of 8 inpatients and 6
      outpatients. The majority of patients had a diagnosis a severe depressive
      episode. 13 patients received bilateral ECT. In 1 case the first 3 sessions were
      unilateral and the rest were bilateral due to patient choice. 9 patients
      consented to ECT; 5 lacked capacity to consent and 1 of those was treated under
      Section 62 of the Mental Health Act. The number of treatments ranged from 0-15
      with an average number of 7. This included 1 patient who did not receive ECT at
      all due to concerns raised by anaesthetist once at the ECT clinic. Reasons for
      stopping ECT included a response being achieved in 5 patients; anaesthetic risk
      in 3; withdrawal of consent in 2; T6 no longer valid in 1; no reason documented
      in 3 patients. Compliance with NICE guidelines was particularly good regarding
      the indications for ECT. An adequate trial of treatment was evidenced prior to
      consideration of ECT. Documentation of the exploration of the risk to benefit
      ratio both amongst the team and with the patient was poor. Assessment of the
      patient after each ECT and on-going cognitive assessment was poor. CONCLUSION:
      This audit highlights the need for sound documentation of our practice. It also
      stresses the need for further clarity regarding the roles and responsibilities of
      the RMO and their team and the ECT team. RECOMMENDATIONS: An ECT Care Pathway
      document has been produced to improve compliance with NICE guidance and improve
      documentation of practice. This document has been introduced for use in the
      Trust. We plan to re-audit for improvement in compliance.

PMID- 21894114
TI  - Post-traumatic stress disorder (PTSD) treatment experience in Bedford East -
      audit and reaudit.
AB  - Post-traumatic stress disorder (PTSD) can develop following exposure to a
      stressful event of an exceptionally threatening or catastrophic nature. Symptoms
      experienced by PTSD suffers can include re-experiencing the trauma through
      intrusive 'flashbacks' and recurrent dreams or nightmares, avoidance of stimuli
      associated with the stressor, hyperarousal, emotional blunting and an inability
      to remember aspects of the period of exposure to the stressor. We performed an
      audit of the treatment of PTSD in patients under the care of the Bedford East
      Mental Health Team to examine the psychological and pharmacological treatments
      currently being used and compared these with data collected in 2008. In summary,
      in the last 2 years there has been an increase in the identification of PTSD
      patients in Bedford East. These patients are a group with high levels of
      comorbidities and risk factors, and are challenging to treat. As a result of
      this, a wide range of agents including antidepressants with augementation, mood
      stabilizers and antipsychotic agents are used in their treatment, many of which
      are outside of NICE guidelines. There appears to be less availability of
      psychological therapy in these patients than we would expect. We discuss reasons
      for this and suggest possible solutions.

PMID- 21894115
TI  - "The case of the Beau-Vallon": mental illnesses of deaf people to the psychiatric
      hospital.
AB  - OBJECTIVE: This article aims to examine data on Psychiatric diagnoses among deaf
      people in comparison with hearing people in the psychiatric hospital in Beau
      Vallon. METHOD: This work proposes to study the diagnostic data from the Summary
      Psychiatric Minimum (Resume psychiatrique minimum: RPM) from the years 2000 until
      2009 from the psychiatric hospital Beau Vallon and for which a hearing problem
      has been highlighted on Axis III. The sample data of the deaf population will be
      compared with the sample of the total population represented by all patients for
      the year 2008. Both samples were found to be equivalent after a Mann-Whitney test
      to study the relationship between two independent samples with quantitative data.
      RESULTS: The results show an overrepresentation of the diagnosis of psychotic
      disorders (40.7% against 29.3%), an equivalence of depressive disorders (18.5%
      against 18%) but bipolar disorders were absent in the deaf while they were found
      in 5.7% of patients with normal hearing, an overrepresentation in the deaf
      population of anxiety disorders (11.1% against 3.4%), intellectual disabilities
      (37% against 13.4% in the hearing population) and an under-representation of
      personality disorders (25.9% against 61.2% in the hearing population) CONCLUSION:
      In this example, several concepts can be put forward to demonstrate bias and
      prejudice in the specific diagnostic support for deaf people with psychiatric
      teams who are not specialized in the treatment of deafness.

PMID- 21894116
TI  - Methadone and lung transplants.
AB  - OBJECTIVES: The aim of this article is to better understand the role of the
      liaison psychiatrist regarding the pulmonary pre-transplantation assessment for a
      patient treated by methadone. METHOD: At the beginning, we collected data
      concerning the different habits of patients requiring pulmonary transplantation.
      Through a literature review, we studied the possible guidelines related to this
      subject, the effects of methadone, the side-effects explaining the psychiatrist's
      concerns. Finally, this problem is involved in the bio-psycho-social model to
      underline the influence of methadone on post-operative prognosis. RESULTS: In our
      database, only 4.3% of patients were treated by methadone. However, this
      addiction is one of the most important stressors for psychiatrists and involves a
      great deal of multidisciplinary staff time. There are absolutely no guidelines on
      this topic. Due to the action of methadone, the pulmonary, cardiac, urologic,
      drug and immune side effects are more understandable. Thanks to clinical labels,
      we are able to handle this dual problem. Different parameters are considered such
      as patient's history, drug addiction, deterioration of physical condition,
      possible surgery and its consequences, choice of treatment to better estimate the
      post-operative prognosis. CONCLUSION: Until now, there is nor indication or
      contra-indication regarding the duration of treatment by methadone for patients
      requiring pulmonary transplantation. The main advantage is the patient's
      stabilization by minimizing possible relapses. This advantage is to compare the
      following major inconvenience: increased confusional risk, delicate management of
      the post-operative pain, negative impact on the immunity. The support, a double
      psychoeducation and the patient's decision making are to be encouraged.

PMID- 21894117
TI  - Adolescents and young adults at ultrahigh risk of psychosis: detection,
      prediction and treatment. A review of current knowledge.
AB  - BACKGROUND: The onset of psychosis is mostly preceded by a prodromal phase in
      which occur a series of various attenuated positive symptoms, negative symptoms
      and functional impairment. Recently, several longitudinal studies have evaluated
      the validity and prediction power of the "prodromal risk syndrome for psychosis",
      which could lead to a better focused management of the patients at real risk of
      developing schizophrenia. At the same time, several authors have studied the
      pharmacological and non-pharmacological interventions for people at ultrahigh
      risk. METHODS AND AIMS: The objective of this review is to establish the status
      of our current knowledge about what is the most sensitive and specific tool to
      predict high risk of psychosis in the young population and which treatments have
      currently proved to be the most effective in the risk versus benefits balance. We
      will try to answer to these questions by reviewing the international literature
      from 2005 until today. RESULTS: Recent studies show significant improvement in
      the identification of individuals at high risk of developing psychosis, using
      validated detection scales such as SIPS and CAARMS, multivariate neuroanatomical
      pattern classification and specific genetic factors. Cognitive Behavioral
      therapy, approach improving social functioning, and Long-Chain Omega-3 Fatty
      Acids appears to be promising alternatives to antipsychotics, for which the
      balance between benefice and adverse side effects seems questionable.
      CONCLUSIONS: Detection of young people at ultrahigh risk of psychosis has
      significantly improved during the last 6 years. The challenge for the next decade
      will be to define a nosologic entity specific and sensitive enough to become a
      diagnostic category by itself, which could lead to specific guidelines for the
      preventive management of psychosis.

PMID- 21894118
TI  - Intensity of symptoms from alcohol withdrawal in alcohol-dependent patients:
      comparison between smokers and non-smokers.
AB  - BACKGROUND: In patients with a dual dependence on alcohol and tobacco, the
      spontaneous discourse among doctors is not to encourage them to consider
      preparing to give up both substances. The argument put forward is that withdrawal
      would be more difficult. We wanted to compare the intensity of withdrawal
      symptoms in patients hospitalised for alcohol detoxification between smokers and
      non-smokers. SUBJECT AND METHODS: We compared patients hospitalised for alcohol
      detoxification who smoke versus non-smokers who received replacement therapy
      through benzodiazepines and not nicotine replacement. The blood pressure and the
      cardiac frequency measure on the first day of hospitalisation, the doses of
      Diazepam dispensed on the first day, and the Clinical Institute Withdrawal
      Assessment of Alcohol Scale Revised (CIWA-Ar) score on the second day were
      compared. RESULTS: A trend emerged whereby smoking patients undergoing alcohol
      detoxification showed higher blood pressure, higher cardiac frequency and
      required higher doses of benzodiazepines on the first day of hospitalisation.
      Patients who smoke also had higher CIWA-Ar scores on the second day of
      hospitalisation. DISCUSSION: From a physiological point of view, the intensity of
      the symptoms of alcoholic withdrawal seems to be greater in hospitalised patients
      who smoke vs. non-smokers in the first two days. Does giving up both substances
      at the same time result in fewer withdrawal symptoms? And in this case, should a
      double replacement be recommended: benzodiazepines and nicotine replacement
      therapy? CONCLUSION: To be able to refine the recommendations on alcohol-tobacco
      dual withdrawal programmes, other studies are needed to compare giving up both
      substances with or without nicotine replacement.

PMID- 21894119
TI  - Audit of antipsychotic prescribing in dementia: Cambridgeshire results and
      lessons learnt.
AB  - BACKGROUND: Behavioural and psychological symptoms in dementia (BPSD) are common
      and distressing. Anti psychotic medication has been shown to have modest efficacy
      but is associated with well documented risks including excess cardiovascular
      events and increased mortality. The current NICE recommendations are that
      antipsychotics should only be prescribed to those with severe BPSD after
      exploring other possible interventions. There should be adequate counselling of
      the patient/family, an explicit risk-benefit analysis and regular review.
      METHODS: As part of the POMH-UK National Audit on antipsychotic prescribing in
      dementia we reviewed the notes of 67 patients in the Cambridgeshire area who had
      a diagnosis of dementia. RESULTS: Of the 67 patients reviewed, only 9 (13.4%)
      were currently being prescribed antipsychotics for BPSD. Of these patients, all
      were living in their own homes and were experiencing multiple distressing target
      symptoms. 5 had been prescribed an antipsychotic for less than 3 months and only
      1 had a total duration of treatment of more than 1 year. There was good evidence
      in all cases that alternative diagnoses and management strategies had been
      explored before prescribing an antipsychotic. However, in none was the full range
      of potential causes or interventions explored. In 6 cases a risk/benefit analysis
      for use of antipsychotic medicine was recorded and in 5 cases there was
      documented discussion of this with family or carers. Of the four patients who had
      been prescribed an antipsychotic for more than 3 months, three had had two or
      more medication reviews. The fourth patient had had a trial of stopping the
      medication. Prescribing of other psychotropic medication was also reviewed.
      Benzodiazepines were used sparingly (7.5%). Of note a significant minority of
      patients (10.4%) were prescribed 3 or more different psychotropic medications.
      CONCLUSION: These results suggest that within this service antipsychotics are
      being used appropriately to enable patients with distressing and difficult
      behaviour to continue to remain at home. They were generally prescribed for a
      short time and reviewed. Areas for improvement include a documented discussion of
      risk in all cases and ensuring that all possible causes of BPSD have been ruled
      out. Regular review of efficacy and tolerability is essential for all
      pharmacological treatments for BPSD particularly for those prescribed multiple
      psychotropic medications.

PMID- 21894120
TI  - Co-morbidity of bipolar affective disorder and obsessive compulsive disorder in a
      Bedford community psychiatry team.
AB  - This is a study of the prevalence and impact of co-existing bipolar affective
      disorder on patients with OCD, and the effect on their management within a
      community psychiatric team. We found that 16% of patients who visited psychiatric
      outpatients with a diagnosis of OCD had co-existing bipolar affective disorder.
      Of these the majority had bipolar affective disorder II (67%). Co-morbidity
      raised a number of challenges to patient management. Compared to the control
      group the patients with co-morbid bipolar affective disorder required a greater
      number of outpatients appointments, had a greater number of hospital admissions,
      were more likely to have been allocated a care coordinator and to have received
      psychological input.

PMID- 21894121
TI  - The Kraepelinian dichotomy in terms of employment outcomes.
AB  - We assess the effectiveness of return to employment, and hence social inclusion
      in patients with chronic schizophrenia and bipolar affective disorder within a
      British community mental health team.

PMID- 21894122
TI  - Discovering new genetic and psychosocial pathways in Major Depressive Disorder:
      the NewMood project.
AB  - The World Health Organisation predicts that Major Depressive Disorder (MDD) will
      be the second greatest contributor to the global burden of disease by 2020,
      however, the neurobiological mechanisms behind the disease and the risk factors
      for it are yet unknown. NewMood (New Molecules for Mood Disorders) was a research
      project funded by the EU, collaborating work from 10 European countries with the
      aim of finding new molecular mechanisms behind MDD to develop more effective
      treatment options. This review explains the aims and objectives of NewMood and
      how it intends to achieve them with regards to the current literature. It also
      outlines two of its most recent projects: genome wide association replication
      study for single nucleotide polymorphisms (SNPs) increasing susceptibility to MDD
      and stress related pathways in depression using the cortisol awakening response
      (CAR). Both of these studies had significant results and could further contribute
      to our current understanding of MDD.

PMID- 21894123
TI  - The present global financial and economic crisis poses an additional risk factor
      for mental health problems on the employees.
AB  - BACKGROUND: The global financial and economic crisis starting in 2007 led to a
      deterioration of several socio-economic determinants of mental health. The aim of
      this cross-sectional study was to examine the impact of the present economic
      crisis on the depression and anxiety levels of the employed in the private and
      public sector in Slovenia. SUBJECTS AND METHODS: Altogether 1592 employees
      completed an internet based self-reported questionnaire. Data about perceived
      impact of the economic crisis, several socio-demographic, socioeconomic, and
      health parameters were collected. Depression symptoms were assessed by the Center
      for Epidemiological Studies-Depression Scale and anxiety symptoms by the
      Spielberger State-Inventory. Regression models were used 1) to explore the
      associations of the economic crisis with the level of depression and anxiety
      symptoms while controlling for some sociodemographic and work characteristic
      variables, and 2) to understand the relationship between some potentially
      important socioeconomic variables and the perception of the economic crisis.
      RESULTS: Depressive and anxiety scores were significantly increased among 590
      (46.6%) employees being affected by the economic crisis. The level of depressive
      symptoms was significantly associated with perceived impact by the crisis, recent
      sick leave, reported injuries sustained at work, benzodiazepine and analgesic
      use, the lack of emotional support, and trust in crisis telephone lines. The
      level of anxiety symptoms yielded the robust association with the level of
      depression symptoms, reported injuries sustained on the way to work and
      education. CONCLUSIONS: The economic crisis poses an additional risk factor for
      mental health problems which clinicians should internalize and become more aware
      of them. Symptoms of depression and anxiety can be masked in high-utilizers of
      medical care with physical complaints or psychoactive drug use.

PMID- 21894125
TI  - Neurocognitive functioning in drug-naive patients with first episode of psychosis
      before and after treatment.
AB  - Cognitive deficit is a core feature of schizophrenia mostly grasping memory,
      psychomotor processing, attention, thinking, and executive functioning and is
      already present in the prodromal phase of the illness and is detected at the
      onset. Recent studies have been focused on the differentiation of cognitive
      functioning in relation to the diagnostic categories, which reveal cognitive
      heterogeneity in schizophrenia and schizophrenia spectrum disorders. The study
      demonstrated that along with changes in the clinical state, specifically, with
      reduction of psychopathological symptoms, patients with schizoaffective disorders
      show more positive dynamics with better chances to back up while in schizophrenia
      the cognitive dysfunction is more defined and less prone to improvement.

PMID- 21894124
TI  - Long term groups of patients with psychosis: physical activity and medical
      treatment.
AB  - AIM: Long term group work with outpatients with psychosis who attended groups in
      the last ten years was evaluated regarding their physical activity, quality of
      life and medication treatment. METHODS: Outpatients with psychosis who attended
      long term psychotherapeutic groups were evaluated regarding their medication,
      quality of life and physical activity. A modified, non-structured, psychoanalytic
      group technique which includes psycho education, cognitive techniques, non
      structural conversation and clarifications was used in group therapy. For
      evaluation purposes Quality of life Bref and a self-designed physical activity
      questionnaire along with clinical observation and Drug Attitude Inventory was
      used. Each patient's medication was noted at the time of the study and the dosage
      was transformed into chlorpromazine equivalents. RESULTS: Several therapeutic
      group factors are important for improving attitudes towards physical activity,
      improving quality of life and attitude towards medication. The physical activity
      questionnaire gave us some preliminary information on our patients' current
      physical activity. We explore the patients' Quality of life, medication and
      attitude towards physical activity. DISCUSSION: The results show that there is a
      relevant correlation between physical activity, quality of life and medication
      treatment. Therefore treatment in a team setting and a multidisciplinary approach
      could lead to the best results in this respect and better physical health of
      patients with psychosis.

PMID- 21894126
TI  - A novel bedside communication tool.
AB  - Effective communication between patients, their families, their carers and health
      care professionals is paramount to the delivery of high quality care. Addressing
      the ideas, concerns and expectations of these groups may improve their healthcare
      experience. We propose that opening a new channel of communication between
      patients, families, carers and healthcare professionals on the wards would
      improve the delivery of healthcare. We present a novel written communication aid-
      the Care Communication Aid (CCA), with preliminary data from secondary and
      tertiary healthcare trials demonstrating its efficacy and shortcomings, and the
      reaction of both recipients and providers of healthcare to this novel approach.

PMID- 21894127
TI  - Neurobiology of bipolar disorder - lessons from migraine disorders.
AB  - Treatment for Bipolar Affective Disorder is at present largely empirical, in the
      lack of a definitive understanding of the biological basis of the condition. Many
      theories have been proposed regarding the underlying neurobiology. These have
      included aetiologies relating to altered neurotrophic factor expression,
      mitochondrial endoplasmic reticulum dysfunction with related calcium changes, and
      loss of inhibitory interneurons. Here an attempt is made to integrate such
      current understanding, in part by considering the changes observed in migraine -
      a condition which has a number of similarities with bipolar disorder.

PMID- 21894128
TI  - An audit to compare patient factors (age, sex, social background & associated
      physical diagnoses) in people with refractory depression in a Bedfordshire
      Community Mental Health Team (BCMHT) being augmented with (A) mirtazepine, (B)
      atypical antipsychotics or (C) both.
AB  - In recent years, there has been particular interest in the use of augmentation as
      a strategy for the treatment of refractory depression. The purpose of this audit
      was to define patient factors among people receiving augmentation therapy with
      either mirtazepine or atypical antipsychotics. We searched an anonymised database
      of patients and identified those with receiving augmentation with mirtazepine
      (group A), atypical antipsychotics (group B) or both (group C). The audit reveals
      some interesting differences in patient factors between the three groups.
      Knowledge about such differences is useful in practical terms because it allows
      doctors in the BCMHT to target therapy for different patients towards their
      specific needs. However, the audit cannot explain the underlying reasons for
      these differences.

PMID- 21894129
TI  - An audit to compare the efficacy of treatment (as indicated by discharge rates
      and reduction in suicidality) among patients with refractory depression in a
      Bedfordshire Community Mental Health Team receiving augmentation therapy with
      either mirtazepine or atypical antipsychotics.
AB  - In recent years, there has been particular interest in the use of augmentation.
      Potential augmentation regimes include the addition of atypical antipsychotics
      (e.g. risperidone/olanzapine) or other antidepressants (e.g. mirtazepine). The
      purpose of this audit was to compare patient outcomes between groups receiving
      different augmentation strategies. Overall we found that augmentation with
      mirtazepine resulted in better outcomes in terms of both discharge rates and in
      terms of reduction in suicidality than augmentation with atypical antipsychotics.

PMID- 21894130
TI  - Is family therapy the most effective treatment for anorexia nervosa?
AB  - INTRODUCTION: Anorexia nervosa is a mental health disorder characterised by
      deliberate weight loss (through restrictive eating, excessive exercise and/or
      purging), disordered body image, and intrusive overvalued fears of gaining
      weight. The National Institute for Clinical Excellence recommends that family
      interventions that directly address the eating disorder should be offered to
      children and adolescents with anorexia nervosa. AIMS: To perform a literature
      review to assess whether family therapy is a more effective intervention than
      other treatments in the management of adolescents with anorexia nervosa. METHOD:
      Search of PubMed, The Cochrane Library and NHS Evidence for randomised controlled
      trials that compared a family intervention with another treatment for anorexia
      nervosa in adolescence. RESULTS AND DISCUSSION: This literature search revealed
      only six randomised controlled trials investigating the use of family therapy in
      the treatment of adolescents with anorexia nervosa, and these all had small
      sample sizes. Some, but not all, of these trials suggest that family therapy may
      be advantageous over individual psychotherapy in terms of physical improvement
      (weight gain and resumption of menstruation) and reduction of cognitive
      distortions, particularly in younger patients. Due to the small sample sizes and
      the significant risk of bias (particularly information bias) in some of the
      studies the evidence in favour of family therapy over individual therapy is weak.
      In the future, larger randomised controlled trials with long term follow-up are
      required to assess whether family therapy is the most effective treatment for
      anorexia nervosa in adolescence.

PMID- 21894131
TI  - What's in a name? - The Psychiatric Identity Conundrum.
AB  - BACKGROUND: The proper label to describe people receiving care has evoked
      considerable debate and controversy among providers and bio-ethicists.
      Fashionable terms in current use include "patient, client, consumer, customer and
      service user." There is little evidence to show that changes in nomenclature
      actually take patients preferences as to how they would like to be addressed into
      account AIMS: This aim of this study is to survey the views of the people with
      learning disability in inpatient settings to establish the term they prefer. This
      is the first study of its kind looking at the views of people with learning
      disability about how they would like to be addressed and to identify factors
      associated with various preferences. METHOD: Approval was obtained from the local
      clinical governance board. The target population covered a tertiary level
      inpatient service including acute assessment and respite services, forensic
      (male/female and low/medium secure services) and CAMHS LD covering the Coventry,
      Warwickshire and Birmingham areas (rural and inner city population). Participants
      were provided with an information sheet on the research project. The
      questionnaire was administered by means of a joint interview carried out by the
      authors of the study. Dictionary definitions were analyzed as to the derivation
      and connotations of various terminologies. A questionnaire was developed which
      was tailored for use in PWLD after consultation with Speech & Language Therapists
      and local peer review. Responses were than analyzed to identify factors
      associated with various preferences. RESULTS: Evidence indicates lack of
      universality in preferences for terms and suggests the need for dialogue about
      preferred terms between service providers and recipients. This study shows a
      preference for the term "patient" in all categories that were measured within an
      LD inpatient setting and very interesting demographic preferences were
      identified. A more differentiated approach may be suggested by taking
      professional background and some demographic characteristics into consideration.
      A positive therapeutic relationship is a fundamental component of psychiatry and
      should take into account patients' preferences regarding how they are addressed
      by professionals.

PMID- 21894132
TI  - Time-travelling and mind-travelling: examining individual differences in self
      projection.
AB  - It has recently been suggested that memory and theory of mind may share the
      characteristic of mentally projecting oneself into another time or place to
      imagine alternative perspectives. This study examines this possible relationship
      by investigating individual differences in performance on a reality monitoring
      task and two mentalising tasks: the faux pas task and the reading the mind in the
      eyes test. Consistent with recent functional neuroimaging studies that have
      observed activity during reality monitoring tasks in the same region of
      prefrontal cortex that was activated in previous mentalising studies, a
      significant positive correlation in performance was observed between memory for
      agency and faux-pas recognition. No correlation between memory and performance on
      the reading the mind in the eyes test was observed. The significance of these
      findings is discussed with respect to the suggestion that memory and theory of
      mind rely on a common set of processes.

PMID- 21894133
TI  - How frequently are atypical antipsychotics used to treat OCD in a British
      community mental health team?
AB  - Obsessive compulsive disorder (OCD) is a condition with a prevalence of around 1
      2% (3-4% in some studies) with a recognised protocol for its treatment produced
      by the national institute for health and clinical excellence (NICE). NICE
      recommends that all patients with OCD are first offered treatment with cognitive
      behavioural therapy (CBT) concentrating on exposure and response prevention (ERP)
      before proceeding to selective serotonin re-uptake inhibitors (SSRIs). Treatment
      may later be augmented with clomipramine and/or an antipsychotic. This study
      focuses on the biological treatment received after, or in parallel to, the
      psychological. We aimed to collate and evaluate the levels of biological
      treatment currently received by OCD outpatients in the Bedford East catchment
      area of SEPT. In particular we wished to establish how many of the patients were
      receiving an atypical antipsychotic as well as maximal SSRIs. Hence we have
      attempted to assess the types of treatment received by patients under our care,
      and the difficulties associated with the treatment of this illness.

PMID- 21894134
TI  - A retrospective audit of referrals of 16-17 year olds with reference to substance
      abuse.
AB  - BACKGROUND: Emerge is an innovative Child and Adolescent Mental Health Service
      that provides support for 16-17 year olds. The team provide a community based
      multi-disciplinary, open access model, texting young people and travelling to
      locations convenient to them. There is an enhanced duty system providing a rapid
      flexible response within working hours. AIMS: To examine the referral data as
      part of the ongoing annual audit cycle and to establish prevalence of alcohol,
      cigarettes and substance use among young people referred to the service. METHOD:
      Data from the case notes was analysed using Statistical Package for Social
      Science. Demographic details, referrer profession, reason for referral, other
      services involved and substance use were examined. RESULTS: There were 437
      patients referred to Emerge between 1/4/2010 and 31/3/2011, and 387 patients were
      accepted while 50 were signposted on. Cases were not accepted if they fell
      outside the age and geographical area, or were not in need of a mental health
      service. Overall, 24% of young people were reported to consume alcohol, 19% used
      cannabis and 9% reported using cigarettes. In all categories there were areas
      where documentation was not complete, and we suggest that these figures are an
      underestimate. CONCLUSION: This data has been fed back to the team, a full
      morning of teaching regarding drugs and alcohol has been delivered. Emerge often
      works with young people who are marginalised and may be harder to reach,
      consequently early sessions require neutral and supportive questions, thus if
      young people do not return after the first appointment, histories may be
      incomplete. The team will be reflecting on the lessons learned and considering
      ways to optimise their work.

PMID- 21894135
TI  - Classification of risk in psychiatry.
AB  - Psychiatric risk-assessments generally quantify risk using broad, categorical,
      indicators (e.g., high-risk, low-risk). We examined reliability of such
      indicators when applied by mental-health professionals. Four versions of a
      questionnaire were used, each specifying a different clinical outcome along with
      a range of different probabilities at which that outcome might occur. Respondents
      classified each probability, allowing a comparison of the level of likelihood at
      which different professionals would apply the terms 'high-risk', 'medium-risk'
      and 'low-risk'. We found little consistency among professionals who assessed risk
      for the same outcomes. Moreover, there were also large and unpredicted
      differences in response-profiles between the 4 clinical outcomes. These findings
      raise concerns about the communication value of current risk-assessment
      terminology.

PMID- 21894136
TI  - Zenith Low Profile AAA endovascular graft and global pivotal clinical trial.

PMID- 21894137
TI  - Cordis INCRAFTTM ultra-low profile AAA stent-graft system.
AB  - Endovascular repair was originally introduced as a less invasive alternative in
      less healthy patients, but potentially lower morbidity has been balanced by
      limited anatomic applicability, as well as inferior long-term device durability.
      The INCRAFTTM endograft was developed with surgical repair in mind, in an attempt
      to capitalize on the anatomic flexibility of traditional procedures. The INCRAFT
      system was designed to address durability issues of older generation devices. At
      the same time it provides a solution for a broad range of patients using a
      limited number of codes needed. The 3-pieces modular system allows precise
      placement at level of the iliacs and aortic neck reducing the risk of
      unintentional coverage of the hypogastric and renal arteries. In addition, the
      ultra-low profile delivery system (13 Fr even for graft main bodies up to 30 mm)
      contributes to increase patient eligibility for endovascular aortic repair and to
      decrease the risk for access complications. When desired, the delivery system can
      be introduced through a percutaneous approach. The initial experience with the
      new endograft showed a highly versatile device that offers a more individualized
      endovascular option to a greater number of patients with abdominal aortic
      aneurysms. The ongoing IN-NOVATION trial and two planned clinical trials (IN
      CEPTION and IN-SPIRATION) will build further understanding of the performance of
      the device allowing for a wider subset of inclusion criteria.

PMID- 21894138
TI  - Infrainguinal disease treatment: to stent or not to stent.
AB  - Infrainguinal endovascular interventions have increasingly played a central role
      in relieving symptoms of claudication and limb salvage over the last decade.
      Multiple modalities currently exist for treating these arteries; however, balloon
      angioplasty with or without stenting still remains the most commonly used
      technique. Despite the concerns regarding the use of stents with stent fractures
      and in-stent restenosis, there is increased evidence from randomized and non
      randomized studies that use of nitinol stents improves patency rates in most
      patients with >5 cm long lesions. However, the optimal endovascular treatment of
      the longest lesions is still debated. Infrapopliteal vessels are still mostly
      treated with balloon angioplasty, but selective use of bare or drug eluting
      stents especially in longer lesions is promising. The role of drug-eluting
      stents, balloons and other debulking procedures for both femoropopliteal and
      infrapopliteal arteries still needs to be further investigated.

PMID- 21894139
TI  - The International E-vita Open Registry: data sets of 274 patients.
AB  - AIM: After the introduction of the hybrid stent-graft "E-vita-open" by the Essen
      group in 1/2005 for one stage repair of complex thoracic aortic disease, the
      International E-vita open Registry was founded in 2008 to study the principles of
      this treatment algorithm and to control reported favorable single center results
      on a large patient data set basis up to six years after the first clinical
      implant. METHODS: Retrospective data work-up after prospective data acquisition
      was achieved by institution of the International E-vita open Registry with
      anonymous registration and calculation at Essen University Hospital. From January
      2005 to December 2010, 274 patients (mean age 60; 74% males) with complex aortic
      disease, 190 with aortic dissection (88 acute (AAD), 102 chronic aortic
      dissection (CAD), and 84 with complex thoracic aortic aneurysm (TAA) were
      included in the studied. RESULTS: Eighty-one out of 274 (30%) patients underwent
      emergency surgery. Stent-graft deployment and arch replacement (238 total, 36
      subtotal) was performed under selective antegrade cerebral perfusion (75 min
      mean). Cardiopulmonary bypass (CPB) and cardiac arrest times were mean 235 and
      134 minutes, respectively. In-hospital mortality was 15% (40/274), 18% for AAD,
      13% for CAD, and 14% for TAA. New strokes were observed in 6% (16/274), spinal
      cord injury in 8% (22/274). The false lumen (FL) was evaluated throughout the
      first hospital stay and at a median follow up time of 59 months after surgery.
      From the first follow up CT-examination to the last, thoracic complete FL
      thrombosis increased from 83% to 93% in AAD, from 72% to 92% in CAD. Full
      exclusion of the aneurysmal disease was achieved in 77% (61/79) during the
      primary hospital stay. CONCLUSION: Favorable single center results could be
      confirmed by an International community of cardiac surgical centers in regard to
      hospital mortality and morbidity, as well as a low postoperative complication
      rate and exclusion of false lumen in aortic dissection.

PMID- 21894140
TI  - Comparison between autogenous brachial-basilic upper arm transposition fistulas
      and prosthetic brachial-axillary vascular accesses for hemodialysis.
AB  - AIM: The aim of this paper was to compare the outcomes of patients undergoing
      autogenous brachial-basilic upper arm transposition fistulas (BBAVF) with
      prosthetic brachial-axillary vascular accesses (BAPTFE) at immediate and medium
      follow-up. METHODS: Retrospective analysis of the aforementioned accesses
      performed in a single-center from 2003 to 2007. Transposition was used in all
      BBAVF performed. Conic prostheses were used in the BAPTFE. Primary and secondary
      patency, patient survival, types of complications and its rates were assessed
      during follow-up. RESULTS: Thirty-six BBAVF and 40 BAPTFE were performed. Both
      groups were well matched for age, gender and comorbidity. BBAVF primary patency
      was 93.5%, 50.4%, 45.8% and 45.8% compared to 80.6%, 64.3%, 46.2% and 31.6% of
      the BAPTFE group at 1, 12, 24 and 36 months of follow-up (P=0.719). BBAVF
      secondary patency was 93.5%, 50.4%, 45.8% and 45.8% compared to 80.6%, 67.7%,
      54.2% and 35.1% of the BAPTFE at the same periods (P=0.902). Patient survival was
      97.2%, 97.2%, 93.2% and 86.5 for BBAVF in contrast to 97.2%, 94.4%, 84.1% and
      79.9% for BAPTFE in the same months (P=0.386). 13.8% of the BBVAF had
      accessibility problems while only 5% of the BAPTFE presented them (P=0.174).
      Infection was more frequent in BAPTFE (0% vs 10%), being the only complication
      near the statistical signification (P=0.071). CONCLUSION: BBAVF offer patency and
      accessibility rates similar to BAPTFE, but lower infectious complications. Thus,
      we consider them as the preferred hemodialysis access when fistulas using the
      cephalic vein have failed or are not possible.

PMID- 21894141
TI  - Endoscopic versus direct vision for saphenous vein graft harvesting in coronary
      artery bypass surgery.
AB  - AIM: Recent reports have suggested harvesting of the greater saphenous vein for
      coronary artery bypass (CABG) using endoscopic techniques (endoscopic) results in
      early graft closure, higher rates of myocardial infarction (MI) and death. We
      explored the impact of this technique performed by experienced operators on
      postoperative morbidities, MI and death in our CABG patients. METHODS: All non
      emergent patients presenting for first time CABG surgery from 2006 to June 2009
      were included. Data pertaining to surgery, readmissions, cardiac catheterization
      and interventions during long term follow-up were extracted from our local STS
      and ACC registries. Linear and logistic regressions with clinical covariates were
      conducted to determine if vein harvest technique group predicted the major
      outcomes. Propensity score matching (PSM) was completed to simulate randomization
      and improve covariate balance across the endoscopic and direct vision groups.
      RESULTS: One thousand nine hundred and eighty-eight (N.=1988) patients were
      evaluated in this study (N.=1734 endoscopic group and N.=254 direct vision
      group). The perioperative major adverse outcomes (mortality within 30 days,
      stroke, reoperation for bleeding, prolonged ventilation and readmission within 30
      days) were 17.8% in the endoscopic group and 25.2% in the direct vision group.
      The rate of leg infections was 0.3% for the endoscopic group and 1.6% for the
      direct vision group. After adjustment for covariates, the direct vision group had
      significantly greater risk for prolonged ventilation (P=0.03), MACE (P=0.02) and
      mortality within 30 days (P=0.01), but only marginally greater risk for leg
      infections (P=0.052). In the isolated CABG patients, operative death was 1% for
      the endoscopic group and 1.7% in the direct vision group (P=0.62). After PSM the
      endoscopic group was similar on all outcomes except for having fewer MACE
      (P=0.04). In a mean follow-up of 22.1+/-10.5 months, there were no significant
      differences in the overall rate and time to event for repeat revascularization,
      death and myocardial infarction. With maximum follow up of 39.6 months, 84 deaths
      were documented (N.=67 endoscopic and N.=17 direct vision). CONCLUSION: The
      outcomes captured by the number of postoperative morbidities, incidence of
      myocardial infarction and/or the rate of death for the endoscopic technique were
      comparable to patients in whom the open techniques was used. There was a trend
      towards a decrease in leg infections with the use of the endoscopic device. Based
      on this study we consider the device safe and effective with experienced
      operators.

PMID- 21894142
TI  - Pericardial synovial sarcoma of the heart; is it always worth operating?
AB  - Synovial sarcoma is a rare malignant soft-tissue tumor that most commonly occurs
      in the extremities of young adults. Primary pericardial synovial sarcoma is
      extremely rare. We report the case of a 37 year old male patient who presented
      with intermittent fever, nocturnal sweating and asthenia. Chest X-ray revealed an
      enlarged cardiac silhouette. Echocardiography identified pericardial effusion and
      a mass compressing the right ventricle. After percutaneous drainage of the
      effusion, the mass was not visible and deemed to have been septations of the
      effusion. Chest computed tomography (CT) did not show the mass visible on the X
      ray. At one month follow-up, the pericardial mass was again visible on
      echocardiography and confirmed by magnetic resonance imaging (MRI). CT-guided
      biopsy showed malignant mesenchymal cells. Complete resection was attempted, but
      not possible due to diffuse infiltration of the epicardium. Histological
      examination of the resected tissue revealed an undifferentiated primary
      pericardial synovial sarcoma. The patient refused adjuvant treatment and died 15
      days later. Surgical resection is considered the cornerstone of treatment of this
      rare type of malignant tumor of the young; our patient presented with a diffusely
      infiltrating tumor which could not be resected and required reoperation for
      tamponade and left pericardectomy. We question whether the choice to attempt
      resection was beneficial.

PMID- 21894143
TI  - Transient loss of binocular vision caused by painless aortic dissection in high
      risk abdominal aortic aneurysm surgery.

PMID- 21894144
TI  - Long term results of percutaneous aortic valve implant in a 90-year-old patient.

PMID- 21894145
TI  - A case of heterotopic heart transplantation with evaluation of cardiac CT
      angiography.

PMID- 21894146
TI  - Spleen tyrosine kinase promotes acute neutrophil-mediated glomerular injury via
      activation of JNK and p38 MAPK in rat nephrotoxic serum nephritis.
AB  - Glomerular antibody deposition induces acute neutrophil-mediated glomerular
      injury via activation of c-Jun amino terminal kinase (JNK) and p38 mitogen
      activated protein kinase (MAPK). However, the link between antibody deposition
      and activation of JNK/p38 MAPK signalling is unclear. This study tested the
      postulate that spleen tyrosine kinase (Syk), which is activated via Fcgamma
      receptor ligation, is required for activation of JNK and p38 signalling and acute
      neutrophil-mediated glomerular injury. We used a Syk inhibitor (SYKi) in rat
      nephrotoxic serum nephritis (NTN) in which neutrophil-mediated glomerular injury
      is dependent upon JNK and p38 signalling. SYKi or vehicle treatment of Sprague
      Dawley rats began 30 min before administration of anti-GBM serum with rats killed
      3 or 24 h later. Immunostaining identified de novo glomerular Syk activation (p
      Tyr 525/526) in untreated NTN, being most prominent in neutrophils. Vehicle and
      untreated NTN exhibited heavy proteinuria and glomerular thrombosis at 24 h with
      P-selectin and fibrin immunostaining within capillaries, glomerular macrophage
      and T cell infiltration, activation of JNK and p38 MAPK signalling, and
      upregulation of glomerular mRNA levels of pro-inflammatory molecules (TNF-alpha,
      NOS2, MMP-12 and CCL2). In contrast, SYKi treatment provided complete protection
      from proteinuria, with a profound reduction in glomerular thrombosis and
      immunostaining for P-selectin and fibrin, and a substantial reduction in
      glomerular mRNA levels of pro-inflammatory molecules. SYKi treatment also reduced
      the acute glomerular neutrophil influx and pro-inflammatory response at 3 h in
      NTN. These protective effects were associated with a significant reduction in
      glomerular JNK and p38 MAPK activation. In addition, activation of Syk, JNK and
      p38 was identified in human biopsy samples of acute crescentic
      glomerulonephritis. In conclusion, this study demonstrates that Syk signalling is
      required for JNK and p38 MAPK signalling and acute neutrophil-dependent
      glomerular injury in rat NTN. These findings identify Syk as a potential
      therapeutic target in antibody-dependent kidney disease.

PMID- 21894147
TI  - Tumor-secreted SDF-1 promotes glioma invasiveness and TAM tropism toward hypoxia
      in a murine astrocytoma model.
AB  - A distinguishing feature of high-grade gliomas is the infiltration of neoplastic
      cells into adjacent brain tissues that mark most of these tumors surgically
      incurable. To study the factors associated with tumor invasion, we established a
      new murine brain tumor model, ALTS1C1 derived from SV40 large T antigen
      transfected astrocytes. This new brain tumor model recapitulates several
      histopathological features of human high-grade glioma including increased
      cellularity, prominent cellular pleomorphism, geographic necrosis, active
      mitosis, and extensive invasion of tumor cells into adjacent brain tissues. More
      importantly, ALTS1C1 expressed a relatively high level of stromal-derived factor
      1 (SDF-1/CXCL12) in vitro and in vivo and higher microvascular density (MVD) in
      vivo. To define the roles of SDF-1 in this tumor model, the expression of SDF-1
      in ALTS1C1 cells was inhibited by specific siRNA. SDF-knockdown ALTS1C1 (SDF(kd))
      cells took longer than parental ALTS1C1 cells to form tumors and in contrast to
      the wild-type tumors they had well-defined regular borders and lacked
      infiltration tracts. The SDF(kd) tumors were also associated with a lower MVD and
      more hypoxic areas. In contrast to parental tumors, the density of F4/80-positive
      tumor-associated macrophages (TAMs) in SDF(kd) tumor was higher in non-hypoxic
      than in hypoxic regions. SDF-1 production by tumor cells therefore seems critical
      for the aggregation of TAMs into areas of hypoxia and tumor invasiveness. This
      study not only provides new insight into the role of SDF-1 in brain tumor
      invasion and the relationship between TAMs and hypoxia, but also provides a new
      preclinical brain tumor model for designing new treatment options for invasive
      cases.

PMID- 21894148
TI  - Erythropoietin improves skin wound healing and activates the TGF-beta signaling
      pathway.
AB  - We could recently report that erythropoietin (EPO) accelerates skin wound healing
      in mice. Now, we provide insight into the molecular mechanisms of this non
      hematopoietic property of EPO analyzing the transforming growth factor (TGF)-beta
      signaling pathway. EPO receptor was found expressed in both non-wounded and
      wounded skin tissue as well as in fibroblasts and keratinocytes. In saline
      treated control animals, wounds exhibited a significant upregulation of TGF-beta1
      and of alpha-smooth muscle actin (alpha-SMA) compared with non-wounded skin. EPO
      treatment accelerated wound epithelialization and induced mRNA expression of TGF
      beta1 and alpha-SMA. In addition, EPO significantly enhanced phosphorylation of
      Smad2 and Smad3 in fibroblasts and also elevated phosphorylation of Smad3 in
      wound tissue. Blockade of TGF-beta using a neutralizing anti-TGF-beta antibody
      attenuated EPO-induced acceleration of wound epithelialization in vivo and
      markedly reversed EPO effects on mRNA expression of TGF-beta1 and alpha-SMA. In
      conclusion, EPO caused activation of the Smad-dependent TGF-beta signaling
      pathway, enhanced differentiation of myofibroblasts, and accelerated skin wound
      closure.

PMID- 21894149
TI  - Early endothelial damage and increased colonic vascular permeability in the
      development of experimental ulcerative colitis in rats and mice.
AB  - The role of endothelial damage and increased vascular permeability (VP) in the
      pathogenesis of ulcerative colitis (UC) has not been investigated. We examined
      using functional, morphologic, and molecular biologic studies whether and to what
      extent the endothelial barrier dysfunction precedes enhanced epithelial
      permeability (EP) and the development of mucosal lesions during the early stages
      of experimental UC. We showed that in rats with iodoacetamide (IA)-induced UC
      increased colonic VP occurs early (ie, 2.6-fold increase at 15 min, P<0.01)
      preceding changes in epithelial barrier permeability. EP was unchanged at 15 and
      30 min after IA administration and was increased 1.9-fold at 1 h and 6.7-fold at
      2 h (both P<0.001) after IA. In the dextran sodium sulfate-induced slowly
      developing UC, colonic VP was significantly increased in 2 days (P<0.05) and EP
      only in 4 days (P<0.05). Mucosal endothelial injury led to hypoxia (P<0.05) of
      colonic surface epithelial cells 30 min after IA administration that was
      associated with increased expressions of transcription factors hypoxia-inducible
      factor-1alpha and early growth response-1. Electron and light microscopy
      demonstrated areas of colonic mucosa with perivascular edema covered by intact
      layer of surface epithelial cells in both rat and mouse models of UC. This is the
      first demonstration in four models of UC that endothelial damage, increased
      colonic VP, perivascular edema, and epithelial hypoxia precede epithelial barrier
      dysfunction that is followed by erosions, ulceration, and inflammation in UC.

PMID- 21894150
TI  - Vision preservation during retinal inflammation by anthocyanin-rich bilberry
      extract: cellular and molecular mechanism.
AB  - Anthocyanin-rich bilberry extract, a plant-derived antioxidant, has been utilized
      as a popular supplement for ocular health worldwide. However, it is unclear
      whether this extract has any biological effect on visual function, and the
      mechanism for such an effect is completely unknown. In this study, we generated a
      mouse model of endotoxin-induced uveitis (EIU) that shows retinal inflammation,
      as well as uveitis, by injecting lipopolysaccharide. We pretreated the mice with
      anthocyanin-rich bilberry extract and analyzed the effect on the retina.
      Anthocyanin-rich bilberry extract prevented the impairment of photoreceptor cell
      function, as measured by electroretinogram. At the cellular level, we found that
      the EIU-associated rhodopsin decreased and the shortening of outer segments in
      photoreceptor cells were suppressed in the bilberry-extract-treated animals.
      Moreover, the extract prevented both STAT3 activation, which induces inflammation
      related rhodopsin decrease, and the increase in interleukin-6 expression, which
      activates STAT3. In addition to its anti-inflammatory effect, the anthocyanin
      rich bilberry extract ameliorated the intracellular elevation of reactive oxygen
      species and activated NF-kappaB, a redox-sensitive transcription factor, in the
      inflamed retina. Our findings indicate that anthocyanin-rich bilberry extract has
      a protective effect on visual function during retinal inflammation.

PMID- 21894151
TI  - A phenotype of early infancy predicts reactivity of the amygdala in male adults.
AB  - One of the central questions that has occupied those disciplines concerned with
      human development is the nature of continuities and discontinuities from birth to
      maturity. The amygdala has a central role in the processing of novelty and
      emotion in the brain. Although there is considerable variability among
      individuals in the reactivity of the amygdala to novel and emotional stimuli, the
      origin of these individual differences is not well understood. Four-month old
      infants called high reactive (HR) demonstrate a distinctive pattern of vigorous
      motor activity and crying to specific unfamiliar visual, auditory and olfactory
      stimuli in the laboratory. Low-reactive infants show the complementary pattern.
      Here, we demonstrate that the HR infant phenotype predicts greater amygdalar
      reactivity to novel faces almost two decades later in adults. A prediction of
      individual differences in brain function at maturity can be made on the basis of
      a single behavioral assessment made in the laboratory at 4 months of age. This is
      the earliest known human behavioral phenotype that predicts individual
      differences in patterns of neural activity at maturity. These temperamental
      differences rooted in infancy may be relevant to understanding individual
      differences in vulnerability and resilience to clinical psychiatric disorder.
      Males who were HR infants showed particularly high levels of reactivity to novel
      faces in the amygdala that distinguished them as adults from all other
      sex/temperament subgroups, suggesting that their amygdala is particularly prone
      to engagement by unfamiliar faces. These findings underline the importance of
      taking gender into account when studying the developmental neurobiology of human
      temperament and anxiety disorders. The genetic study of behavioral and biologic
      intermediate phenotypes (or 'endophenotypes') indexing anxiety-proneness offers
      an important alternative to examining phenotypes based on clinically defined
      disorder. As the HR phenotype is characterized by specific patterns of reactivity
      to elemental visual, olfactory and auditory stimuli, well before complex social
      behaviors such as shyness or fearful interaction with strangers can be observed,
      it may be closer to underlying neurobiological mechanisms than behavioral
      profiles observed later in life. This possibility, together with the fact that
      environmental factors have less time to impact the 4-month phenotype, suggests
      that this temperamental profile may be a fruitful target for high-risk genetic
      studies.

PMID- 21894153
TI  - Pharmacogenetics of antipsychotic-induced weight gain: review and clinical
      implications.
AB  - Second-generation antipsychotics (SGAs), such as risperidone, clozapine and
      olanzapine, are the most common drug treatments for schizophrenia. SGAs presented
      an advantage over first-generation antipsychotics (FGAs), particularly regarding
      avoidance of extrapyramidal symptoms. However, most SGAs, and to a lesser degree
      FGAs, are linked to substantial weight gain. This substantial weight gain is a
      leading factor in patient non-compliance and poses significant risk of diabetes,
      lipid abnormalities (that is, metabolic syndrome) and cardiovascular events
      including sudden death. The purpose of this article is to review the advances
      made in the field of pharmacogenetics of antipsychotic-induced weight gain
      (AIWG). We included all published association studies in AIWG from December 2006
      to date using the Medline and ISI web of knowledge databases. There has been
      considerable progress reaffirming previous findings and discovery of novel
      genetic factors. The HTR2C and leptin genes are among the most promising, and new
      evidence suggests that the DRD2, TNF, SNAP-25 and MC4R genes are also prominent
      risk factors. Further promising findings have been reported in novel
      susceptibility genes, such as CNR1, MDR1, ADRA1A and INSIG2. More research is
      required before genetically informed, personalized medicine can be applied to
      antipsychotic treatment; nevertheless, inroads have been made towards assessing
      genetic liability and plausible clinical application.

PMID- 21894152
TI  - Epigenetic regulation of the BDNF gene: implications for psychiatric disorders.
AB  - Abnormal brain-derived neurotrophic factor (BDNF) signaling seems to have a
      central role in the course and development of various neurological and
      psychiatric disorders. In addition, positive effects of psychotropic drugs are
      known to activate BDNF-mediated signaling. Although the BDNF gene has been
      associated with several diseases, molecular mechanisms other than functional
      genetic variations can impact on the regulation of BDNF gene expression and lead
      to disturbed BDNF signaling and associated pathology. Thus, epigenetic
      modifications, representing key mechanisms by which environmental factors induce
      enduring changes in gene expression, are suspected to participate in the onset of
      various psychiatric disorders. More specifically, various environmental factors,
      particularly when occurring during development, have been claimed to produce long
      lasting epigenetic changes at the BDNF gene, thereby affecting availability and
      function of the BDNF protein. Such stabile imprints on the BDNF gene might
      explain, at least in part, the delayed efficacy of treatments as well as the high
      degree of relapses observed in psychiatric disorders. Moreover, BDNF gene has a
      complex structure displaying differential exon regulation and usage, suggesting a
      subcellular- and brain region-specific distribution. As such, developing drugs
      that modify epigenetic regulation at specific BDNF exons represents a promising
      strategy for the treatment of psychiatric disorders. Here, we present an overview
      of the current literature on epigenetic modifications at the BDNF locus in
      psychiatric disorders and related animal models.

PMID- 21894156
TI  - Update on the harmonisation of disability data collection in UK surveys (part 1).
AB  - BACKGROUND: This article reports progress to date in the development of new
      National Statistics harmonised questions: measuring disability in established
      national social survey sources using a face-to-face interviewing mode of data
      capture. The harmonisation of these questions across these survey sources will
      enhance the availability of consistent disability statistics to government and
      the wider user community.This work began in response to the recommendation of the
      Review of Equality Data published in 2007: to develop and apply a principled
      approach to data collection to meet future data needs, following the introduction
      of equality legislation in 2010. It also contributes to improving international
      comparability, by better meeting the definitions for measures of long-standing
      illness and disability derived from the European Union's Statistics on Income and
      Living Conditions (EU-SILC).Further work is currently being undertaken to adapt
      questions for use in surveys applying different methods of data capture, such as
      paper-based and on-line surveys.The project also developed questions which
      measure disability as a restriction in participation in key areas of life such as
      employment, and the self-perceived social barriers affecting participation (that
      is aspects of society and the physical environment, which do not take adequate
      account of the needs of people with impairments). However, at the time of
      writing, a finalised standard had not been agreed: these data inputs will be
      reported on in a future Health Statistics Quarterly article. METHODS: The
      National Statistics Harmonisation Group (NSHG) and its Health, Disability and
      Carers Sub-Group contain representation across government, related public sector
      bodies and academia. These groups agreed the following project objectives for
      disability data harmonisation:a) Establish a conceptual framework for disability
      definitionb) Develop question inputs to measure the definition for use in social
      surveys using a face-to-face interviewing method of data capturec) Test the
      performance of these questions for interpretability and consistency with
      established sources, and refine questions, where indicated, through the findings
      of testing and consultationd) Recommend harmonised standards for implementation
      across sourcesA process of question suite development included: user
      consultation, which gathered cross-sector views to clarify and prioritise data
      needs; cognitive testing, which guided question formats, content and terminology,
      and interviewer probes and instructions. The findings of these exercises were
      used in the construction of questions which were subsequently field tested for
      coherence with other data sources and described in an accompanying article in
      this issue of Health Statistics Quarterly. RESULTS: The definition of disability
      developed to harmonise standard data inputs and outputs is founded on the
      Disablement Process (Verbrugge and Jette 1994), and the bio-psycho-social model
      of disability used in the International Classification of Functioning, Disability
      and Health (ICFDH) (WHO, 2001). This model presents disability as a process
      bringing together medical, societal and individual factors which affect daily
      activities and participation and disentangles concepts of illness, impairment and
      disability. Disability is defined as restriction in activities and participation
      related to the interaction between functional impairment and the provision of
      supports (personal, mechanical and environmental/societal).The results of
      cognitive testing found issues with the proposed question formats, interpretation
      of key terms such as 'disability' and sensitivities to the negative focus of
      questions; the researchers made a number of recommendations to improve the flow
      of questions and improve interpretation, including better signposting and use of
      interviewer probes and instructions, and changes to the terminology used in the
      body of questions and their response categories. CONCLUSIONS: The extensive
      consultations undertaken, including government departments, other public sector
      bodies, academia and third sector organisations, demonstrates a clear commitment
      on the part of the Health, Disability and Carers Harmonisation Sub-Group to
      gather a wide range of views to identify the deficiencies in existing data inputs
      to social survey data sources; guide priorities as equitably as possible to meet
      the variety of needs expressed; and to lessen the sensitivities associated with
      existing question terminology when drafting question inputs.The application of
      respected conceptual frameworks and internationally recognised definitions and
      classifications to the data needs identified, and the modifications suggested
      following cognitive testing has given the draft questions for field testing a
      stronger relevance to the concept of disability advocated in the Prime Minister's
      Strategy Unit Report 'Improving the Life Chances of Disabled People' and
      championed in the Office for Disability Issues Equality 2025 agenda.

PMID- 21894157
TI  - Update on the harmonisation of disability data collection in UK surveys (part 2).
AB  - BACKGROUND: This article reports on the field testing work undertaken, leading to
      the proposals for a primary harmonised standard for disability data inputs:
      designed to derive statistical measures of disability from social surveys using a
      face-to-face mode of data capture. These proposals were submitted to the National
      Statistics Harmonisation Group (NSHG) for approval in December 2010. The proposed
      primary harmonised standard data inputs are designed to meet the data needs
      arising from the equality legislation introduced in 2010 and improve
      international comparability: by better meeting the definitions for measures of
      longstanding illness and disability derived from the European Union's Statistics
      on Income and Living Conditions (EU-SILC). METHODS: Field testing was conducted
      during two discrete periods: between October 2009 and February 2010 for stage 1
      testing, and between May and July 2010 for stage 2 testing. The Office for
      National Statistics (ONS) Opinions Survey acted as the data collection vehicle
      and the design was a split sample in each case. In stage 1, question suite
      variants were compared, together with the Family Resources Survey (FRS)
      Disability Discrimination Act module running on the Opinions Survey in equivalent
      months. The second stage also applied a split sample to compare the revised
      proposed harmonised questions with the question on disability planned for the
      2011 Census. Derivations of disability to meet measures required under the
      national Equality Act legislation and the European Union-Statistics on Income and
      Living Conditions were applied to field-test estimates to assess coherence with
      contemporaneous external sources. RESULTS: The field test results found good
      comparability with estimates of disability used in the FRS publications and with
      the field tested 2011 Census disability question.In stage 1 testing, the measure
      of disability derived from the version 1 suite was closer to the FRS measure of
      disability used in FRS publications than that derived from version 2's questions.
      In stage 2, the proximity of the measure derived from the proposed harmonised
      questions to the FRS measure of disability improved, with a 0.5 percentage point
      difference.The stage 2 measure of disability was found to be consistent with the
      EU-SILC measure of disability in 2009 for the UK published on the Eurostat
      website. Furthermore, the harmonised questions produced a similar estimate of
      disability to the 2011 Census question, also field tested concurrently with the
      proposed harmonised questions. CONCLUSION: The harmonised questions tested
      provide appropriate data inputs to measure persistent illness, impairment and
      disability, consistent with the components of disability used in the disablement
      process and the International Classification of Functioning Disability and
      Health. Their implementation across social survey data sources using a face-to
      face mode of data capture will enhance the consistency of statistical measurement
      and their relevance to the data requirements embodied in national Equality
      legislation and the EU-SILC European regulation.List of Tables, 33.

PMID- 21894158
TI  - Metabolic syndrome is associated with increased risk of recurrent colorectal
      adenomas in Korean men.
AB  - OBJECTIVE: Because of the high incidence of recurrent colorectal adenomas,
      regular surveillance by colonoscopy is recommended. However, there is still a
      shortage of information on the factors that influence the incidence of recurrent
      colorectal adenomas in patients with a history of these lesions. The aim of this
      study was to determine the association between the development of recurrent
      colorectal adenomas, metabolic syndrome and obesity. SUBJECTS AND METHODS: The
      hospital-based cohort was composed of 193 patients who had recurrent colorectal
      adenomas removed between January 2002 and December 2003. The Cox proportional
      hazard model was used to determine hazard ratio (HR) and 95% confidence interval
      (CI) between obesity, metabolic syndrome and other factors, and the incidence of
      recurrent adenomatous polyps. RESULTS: The mean follow-up period was 4.8 person
      years. In all, 78 of the patients (40.4%) had recurrent colorectal adenomas. In
      the overall recurrent adenoma group, significant associations between metabolic
      syndrome (HR, 1.33; 95% CI, 1.02-1.73), waist circumference (WC) >= 90 cm (HR,
      1.42; 95% CI, 1.06-1.90) and waist-hip ratio (WHR) >= 0.9 (HR, 2.03; 95% CI, 1.55
      2.68) were found. Moreover, advanced adenomas were significantly associated with
      metabolic syndrome (HR, 2.81; 95% CI, 1.86-4.25), body mass index >= 25 kg m(-2)
      (HR, 2.69; 95% CI, 1.64-4.42), WC (HR, 2.16; 95% CI, 1.31-3.54) and WHR (HR,
      1.99; 95% CI, 1.28-3.11). In addition, current smoking (HR, 2.60; 95% CI, 1.09
      6.25) and alcohol consumption (HR, 2.20; 95% CI, 1.10-4.39) were also
      significantly associated with recurrent advanced adenoma. CONCLUSION: Metabolic
      syndrome and obesity were significantly associated with the development of
      recurrent colorectal adenomas in Korean adult males. Furthermore, these
      associations were more strongly associated with advanced adenomas.

PMID- 21894159
TI  - PGC1alpha gene Gly482Ser polymorphism predicts improved metabolic, inflammatory
      and vascular outcomes following bariatric surgery.
AB  - AIMS/HYPOTHESIS: Bariatric surgery is currently employed as an effective approach
      to treat class III obesity and class II obesity with co-morbidities.
      Unfortunately, the general anthropometric and metabolic outcomes of the surgery
      are not homogeneous, and defining the eligibility criteria that allow for a more
      precise prediction of the outcomes of this invasive procedure will refine the
      selection of patients. Here we tested the hypothesis that the Gly482Ser
      polymorphism of the ppargc1a gene would predict different outcomes following
      bariatric surgery. METHODS: Fifty-five patients (26 Gly/Gly and 29
      Gly/Ser+Ser/Ser) selected for the Roux-en-Y gastric bypass according to the
      National Institutes of Health Consensus Statement criteria were followed up for 1
      year, monitoring their anthropometric, metabolic and inflammatory parameters.
      RESULTS: Patients with the Gly482Ser polymorphism had significantly improved
      reductions in the waist/hip ratio, fasting blood glucose, C-reactive protein,
      blood leukocyte count, serum interleukin-6 and intima-media thickness of the
      carotid artery, as compared with Gly/Gly patients. CONCLUSIONS/INTERPRETATION:
      Thus, the Gly482Ser polymorphism may predict a more favorable metabolic and
      inflammatory outcome for obese patients submitted to bariatric surgery, leading
      to a reduced atherosclerotic risk.

PMID- 21894160
TI  - Regulation of glucose/lipid metabolism and insulin sensitivity by interleukin-4.
AB  - OBJECTIVE: Abundant evidence has demonstrated that long-term cytokine-mediated
      inflammation is a risk factor for obesity and type 2 diabetes mellitus (T2DM).
      Our previous study reveals a significant association between promoter
      polymorphisms of Th2-derived cytokine interleukin-4 (IL-4) and T2DM, which
      suggests possible roles of IL-4 in metabolism. In this study, we focused on
      examining the putative regulation of glucose and lipid metabolism by IL-4.
      METHODS: C57BL/6 mice were intraperitoneally injected with either adenovirus
      containing full-length IL-4 encoding gene (AdIL-4) or recombinant IL-4 for
      mimicking the status of transient and long-term IL-4 overexpression,
      respectively, and the effects of the overexpressed IL-4 to glucose/lipid
      metabolism and insulin sensitivity were subsequently investigated. RESULTS: Our
      results reveal that IL-4 improves insulin sensitivity and glucose tolerance
      through upregulating Akt phosphorylation while attenuating GSK-3beta activities.
      IL-4 is also involved in lipid metabolism by inhibiting lipid accumulation in fat
      tissues, which lead to decreased weight gain and fat mass. CONCLUSIONS: Our
      results suggest that IL-4 regulates glucose and lipid metabolism by promoting
      insulin sensitivity, glucose tolerance and inhibiting lipid deposits. This study
      uncovers the novel roles of IL-4 in metabolism and provides new insights in the
      interaction between cytokines/immune responses, insulin sensitivity and
      metabolism.

PMID- 21894161
TI  - Relation of regional gray and white matter volumes to current BMI and future
      increases in BMI: a prospective MRI study.
AB  - OBJECTIVE: This study tested whether global and regional brain volumes correlated
      with body mass index (BMI) and increases in BMI over 1-year follow-up. METHODS: A
      total of 83 young females (M age=18.4, s.d.=2.8; BMI range=17.3-38.9) were
      scanned using magnetic resonance imaging. Voxel-based morphometry was used to
      assess global brain volume and regional gray matter (GM) and white matter (WM)
      volumes in regions implicated in taste, reward and inhibitory control. RESULTS:
      Obese participants had less total GM volume than lean and overweight
      participants. Obese participants had lower total WM volume than overweight
      participants. BMI correlated with higher WM volumes in the middle temporal gyrus,
      fusiform gyrus, parahippocampal gyrus, Rolandic operculum and dorsal striatum.
      Trend-level reduced GM volumes in the superior frontal gyrus and middle frontal
      gyrus were related to increases in BMI over 1-year follow-up. CONCLUSION:
      Findings suggest that BMI is related to global and regional differences in brain
      matter volume in female adolescents. Most importantly, findings suggest that low
      GM volume in regions implicated in inhibitory control are related to future
      weight gain. Results taken in conjunction with prior findings suggest that
      abnormalities in regional GM volumes, but not WM volumes, increase the risk for
      future weight gain and abnormalities in regional WM volumes, but not GM volumes,
      are secondary to weight gain.

PMID- 21894162
TI  - Induction of fatty acid oxidation resists weight gain, ameliorates hepatic
      steatosis and reduces cardiometabolic risk factors.
AB  - OBJECTIVE: Fatty acid oxidation has been implicated in amelioration of obesity by
      burning off excessive accumulated lipid. BPR697, a peripheral cannabinoid
      receptor 1 (CB1) antagonist, elevated fat oxidation without added energy
      expenditure. Its impact on food intake, body weight changes and metabolic
      alterations were examined in rats fed standard chow and in diet-induced obesity
      (DIO) mice. MATERIALS AND METHODS: CB1 agonist-induced hypothermia and analgesia
      responses were measured to examine the brain activity of BPR697. The acute
      effects of BPR697 on food intake, body weight change and post-absorptive
      metabolic profiles were investigated in rats. Energy utilization with BPR697 was
      examined by indirect calorimetry. Chronic treatment of DIO mice was used to
      evaluate the long-term effects of BPR697. RESULTS: Distribution of BPR697 was
      significantly biased in favor of the periphery instead of the brain, as shown by
      its low brain/plasma concentration ratio and confirmed by the negative response
      of BPR697 in CB1 agonist-induced hypothermia and analgesia. When administered to
      rats at 20 mg kg(-1), BPR697 showed a unique spectrum of effects with significant
      weight loss without altered food intake. Furthermore, BPR697 increased serum
      levels of free fatty acids and ketone bodies and reduced hepatic lipid
      accumulation with preservation of liver glycogen in postprandial rats. Indirect
      calorimetric profiling of BPR697 revealed a similar trend, shifting whole-body
      energy catabolism toward fat oxidation, but without elevated energy expenditure.
      In DIO mice with chronic treatment, animals treated with BPR697 at 20 mg kg(-1)
      resisted weight gain and showed a reduction of high-fat-induced cardiometabolic
      abnormalities such as hyperglycemia, abdominal fat and liver steatosis.
      CONCLUSION: The induction of fatty acid oxidation without concomitant elevation
      of energy expenditure by the peripheral CB1 antagonist BPR697 is sufficient to
      cause substantial weight loss in chow-fed rats. In the presence of high-dietary
      fat intake, BPR697 resists weight gain and alleviates obesity-related
      cardiometabolic risk factors.

PMID- 21894163
TI  - Determining the optimal method for proteinuria detection in chronic spinal cord
      injury.
AB  - STUDY DESIGN: A retrospective analysis. OBJECTIVES: The objective of this study
      is to determine whether dipstick protein analysis (DSP) or random urine
      protein:creatinine ratios (UPC) are accurate in predicting clinical proteinuria
      in the chronic spinal cord injury (SCI) population. METHODS: A retrospective
      analysis was performed in 219 veterans with SCI, comparing DSP and 24-h urine
      protein excretion. Sensitivity, specificity, predictive values (PV) and receiver
      operator characteristic (ROC) curves of DSP in predicting clinical proteinuria
      were calculated with and without correction for specific gravity (SG). A
      prospective study was also performed in 62 SCI patients, comparing the UPC and 24
      h urines. Sensitivity, specificity, PV and ROC curves of UPC in predicting
      clinical proteinuria were calculated. RESULTS: Any level of positive DSP had high
      specificity, but low sensitivity, for detecting the presence of clinical
      proteinuria. ROC curves of DSP for identifying clinical proteinuria yielded area
      under the curve of 0.749 (95% confidence interval 0.699-0.794), and adjustment
      for SG did not significantly improve accuracy. A UPC of <0.3 was sensitive with a
      high negative PV for ruling out clinical proteinuria, whereas a ratio >0.8 was
      specific with a high positive PV. A UPC between 0.3-0.8 had an intermediate
      sensitivity and specificity. CONCLUSION: Urine collections of 24-h are still
      needed in the chronic SCI population for accurate detection of clinically
      significant proteinuria. DSP may not reliably detect low-grade clinical
      proteinuria, whereas a UPC below 0.3 may be used to rule out clinical range
      proteinuria.

PMID- 21894164
TI  - An evaluation of the muscle-bone unit theory among individuals with chronic
      spinal cord injury.
AB  - STUDY DESIGN: Cross-sectional observation. OBJECTIVES: To explore the association
      between muscle size and function, and indices of bone strength among a sample of
      adults with chronic spinal cord injury (SCI). SETTING: Ontario, Canada. METHODS:
      Sixty-five participants (n=47 men) with chronic SCI (C1-T12 American Spinal
      Injury Association Impairment Scale (AIS) A-D) were recruited, mean+/-s.d. age
      49.4+/-12.8 years and years post-injury 14.3+/-10.7. Muscle cross-sectional area
      (CSA) and indices of bone strength at the distal tibia and tibia shaft were
      measured by peripheral quantitative computed tomography. Muscle CSA was
      multiplied by tibia length to obtain muscle-bending moment (MBM), a surrogate of
      torque. Plantar flexor components of the lower-extremity motor scores (pf-LEMS)
      were used as clinical measures of muscle function. Pearson's correlations (r)
      were used to determine the strength of relationships. RESULTS: Correlations were
      found between MBM and indices of bone strength at the distal tibia and tibia
      shaft (r=0.44-0.56), as well as between pf-LEMS and indices of bone strength at
      the distal tibia and tibia shaft (r=0.37-0.71). pf-LEMS had a stronger
      association with bone variables at the distal tibia compared with MBM (r=0.6 vs
      r=0.4). All relationships between muscle and bone remained significant when
      controlling for the duration of injury. CONCLUSION: It appears that lower limb
      muscle size and function are more strongly correlated with bone strength indices
      at the distal tibia than at the tibia shaft among individuals with SCI. The
      relationships between muscle and bone are clinically important, as muscle CSA and
      strength (motor scores) are potentially amenable to rehabilitation
      intervention(s).

PMID- 21894165
TI  - Comparing and contrasting knowledge of pressure ulcer assessment, prevention and
      management in people with spinal cord injury among nursing staff working in two
      metropolitan spinal units and rehabilitation medicine training specialists in a
      three-way comparison.
AB  - AIM: To assess for differences in knowledge of pressure ulcer (PU) prevention and
      management among nurses working in two metropolitan spinal cord injury (SCI)
      units, and between nurses and rehabilitation registrars (doctors). BACKGROUND:
      There is anecdotal evidence of wide variation in PU management. An understanding
      of current knowledge is fundamental to evidence-based practice implementation.
      METHODS: This was a prospective survey, using a multiple choice question format
      developed with nurse wound specialists. A total of 10 questions assessed PU
      prevention and 10 assessed management. It was distributed to nurses working at
      the spinal units and rehabilitation registrars. The results from the groups were
      analysed for similarities and differences using one- and two-way analysis of
      variance (ANOVA) tests and tests for significance of specific linear combinations
      of group means. RESULTS: The response rate was 79% (19/24) and 71% (20/ 28) from
      the two SCI units, and 46% (13/28) from doctors. Doctors performed better than
      nurses on prevention questions (P<0.005) but worse on management (P<0.05). There
      was a significant difference in management knowledge (P<0.001) between nurses
      working in the two units but not in prevention knowledge (P<0.5) and
      interestingly years of experience did not correlate with performance (P<0.2 for
      prevention and P<0.5 for management questions). CONCLUSIONS: Rehabilitation
      registrars score better in prevention questions, but poorer in management
      questions, which reflects academic rather than experiential knowledge. There are
      also differences in management knowledge among nurses, based on work area rather
      than years of experience. Although knowledge does not necessarily reflect
      practice, this calls for better standardisation and implementation of wound
      management pathways.

PMID- 21894166
TI  - Correlation of heart rate at lactate minimum and maximal lactate steady state in
      wheelchair-racing athletes.
AB  - STUDY DESIGN: Prospective, experimental study. OBJECTIVE: To investigate whether
      the heart rate (HR) at lactate minimum (LMHR)determined by means of a HR-guided
      lactate minimum test (LMT) corresponds to the HR at maximal lactate steady state
      (MLSS) in wheelchair-racing athletes. SETTING: Institute of Sports Medicine.
      METHODS: Eight well-trained wheelchair-racing athletes (mean age: 33+/-12 years;
      height: 169+/-12 cm; body mass: 59+/-11 kg; VO(2peak): 2.76+/-0.73 l min(-1))
      completed a HR-guided LMT on a treadmill in their own racing wheelchair.
      Subsequently, exercise intensity at MLSS and corresponding HR were determined by
      means of several endurance tests on different days. RESULTS: All measured
      parameters (HR, speed, blood lactate, oxygen consumption and rating of perceived
      exertion) revealed significantly higher values at MLSS compared with values at
      lactate minimum (LM). However, there were highly significant correlations
      (r=0.914, P=0.002) between LMHR and HR at MLSS (163+/-6 versus 172+/-7 b.p.m.) as
      well as for speed (r=0.935, P=0.001) and blood lactate (r=0.944, P<0.001) at LM
      versus MLSS. The correlation for oxygen consumption (r=0.798, P=0.018) at LM
      versus MLSS was lower yet significant. CONCLUSIONS: There exists a close
      relationship between LMHR and HR at MLSS in wheelchair racing. This allows the
      prediction of MLSS based on a single exercise test in this special group of
      athletes. For practical use during daily training, routine HR at MLSS can be
      assumed to be 8-9 b.p.m. above the LMHRin wheelchair-racing athletes.

PMID- 21894167
TI  - Biotechnology: metal-like conductivity in microbial nanowires.

PMID- 21894168
TI  - Symbiosis: market economics in plant-fungus relationships.

PMID- 21894170
TI  - Bacterial secretion: coupled translation of effector-chaperone partners.

PMID- 21894169
TI  - Under the sea: microbial life in volcanic oceanic crust.
AB  - Exploration of the microbiology in igneous, 'hard rock' oceanic crust represents
      a major scientific frontier. The igneous crust harbours the largest aquifer
      system on Earth, most of which is hydrologically active, resulting in a
      substantial exchange of fluids, chemicals and microorganisms between oceanic
      basins and crustal reservoirs. Study of the deep-subsurface biosphere in the
      igneous crust is technically challenging. However, technologies have improved
      over the past decade, providing exciting new opportunities for the study of deep
      seated marine life, including in situ and cross-disciplinary experimentation in
      microbiology, geochemistry and hydrogeology. In this Progress article, we
      describe the recent advances, available technology and remaining challenges in
      the study of the marine intraterrestrial microbial life that is harboured in
      igneous oceanic crust.

PMID- 21894171
TI  - Blk haploinsufficiency impairs the development, but enhances the functional
      responses, of MZ B cells.
AB  - Blk was identified two decades ago as a B-cell-specific member of the Src family
      of tyrosine kinases. Recent studies, however, have discovered that Blk is
      expressed in many cell types outside of the B lineage, including early thymic
      precursors, interleukin-17-producing gammadelta T cells and pancreatic beta
      cells. In light of these recent discoveries, we performed a more comprehensive
      analysis of Blk expression patterns in hematopoietic cells and found that Blk is
      differentially expressed in mature B-cell subsets, with marginal zone (MZ) B
      cells expressing high levels, B1 B cells expressing intermediate-to-high levels
      and follicular (FO) B cells expressing low levels of Blk. To determine whether
      these differences in Blk expression levels reflected differential requirements
      for Blk in MZ, B1 and FO B-cell development, we analyzed the effects of reducing
      and eliminating Blk expression on B-cell development. We report that both Blk
      haploinsufficiency and Blk deficiency impaired the generation of MZ B cells.
      Moreover, although there were fewer MZ B cells in Blk(+/-) and Blk(-/-) mice as
      compared with Blk(+/+) mice, Blk-mutant MZ B cells were hyper-responsive to B
      cell receptor stimulation, both in vitro and in vivo. Thus, this study has
      revealed a previously unappreciated role for Blk in the development and
      activation of MZ B cells.

PMID- 21894172
TI  - Immunoglobulin light chain, Blimp-1 and cytochrome P4501B1 peptides as potential
      vaccines for AL amyloidosis.
AB  - Amyloid light chain (AL) amyloidosis is a lethal disorder characterized by the
      pathologic deposition of clonal plasma cell-derived, fibrillogenic immunoglobulin
      light chains in vital organs. Current chemotherapeutic regimens are problematic
      in patients with compromised organ function and are not effective for all
      patients. Here, a platform of computer-based prediction and preclinical mouse
      modeling was used to begin development of a complementary, immunotherapeutic
      approach for AL amyloidosis. Three peptide/MHC I-binding algorithms identified
      immunogenic peptides from three AL plasma cell-associated proteins: (1)
      amyloidogenic lambda6 light chains, (2) CYP1B1, a universal tumor antigen hyper
      expressed in AL plasma cells and (3) B lymphocyte-induced maturation protein 1
      (Blimp-1), a transcription factor required for plasma cell differentiation. The
      algorithms correctly predicted HLA-A(*)0201-binding native and heteroclitic
      peptides. In HLA-A2 transgenic mice, these peptides, given individually or in
      combination, induced potent CTL which kill peptide-loaded human lymphoma cells
      and/or lymphoma cells producing target protein. Blimp-1 peptide-immunized mice
      exhibited a reduced percentage of splenic, lymph node and bone marrow plasma
      cells and a decrease in the absolute number of splenic plasma cells demonstrating
      (1) presentation of target peptide by endogenous plasma cells and (2) appropriate
      CTL homing to lymphoid organs followed by killing of target plasma cells. These
      studies suggest that AL amyloidosis, with its relatively low tumor cell burden,
      may be an attractive target for peptide-based multivalent vaccines.

PMID- 21894174
TI  - Preoperative weight change and risk of adverse outcome following radical
      prostatectomy: results from the Shared Equal Access Regional Cancer Hospital
      database.
AB  - BACKGROUND: We examined the relationship between weight change in the year before
      radical prostatectomy (RP) and biochemical recurrence (BCR) and adverse
      pathology. METHODS: We abstracted data from 359 men undergoing RP in the SEARCH
      (Shared Equal Access Regional Cancer Hospital) database between 2001-2007.
      Logistic regression and Cox proportional hazards models were used to test the
      association between weight change in the year before surgery and adverse
      pathology and BCR, respectively. RESULTS: In all, 152 (42%) men gained weight,
      193 (54%) lost weight and 14 (4%) had the same weight. Among weight gainers,
      median gain was 2.4 kg and among weight losers, median loss was 2.7 kg. As a
      continuous variable, weight change was not associated with adverse pathology or
      BCR (all P>0.05). In secondary analysis, on multivariate analysis, men gaining >=
      2.5 kg were at higher BCR risk (hazards ratio=1.65, 95% confidence interval (CI):
      1.03-2.64, P=0.04) while weight loss >= 2.5 kg was not associated with BCR
      (hazards ratio=0.83, 95% CI: 0.54-1.29, P=0.41). CONCLUSIONS: As a continuous
      variable, weight change was not associated with outcome. In secondary hypothesis
      generating analyses, weight gain >= 2.5 kg in the year before surgery, regardless
      of final body mass index, was associated with increased BCR following RP. If
      validated, these data suggest weight gain >= 2.5 kg may promote prostate cancer
      progression.

PMID- 21894173
TI  - ISCOMATRIX vaccines mediate CD8+ T-cell cross-priming by a MyD88-dependent
      signaling pathway.
AB  - Generating a cytotoxic CD8(+) T-cell response that can eradicate malignant cells
      is the primary objective of cancer vaccine strategies. In this study we have
      characterized the innate and adaptive immune response to the ISCOMATRIX adjuvant,
      and the ability of vaccine antigens formulated with this adjuvant to promote
      antitumor immunity. ISCOMATRIX adjuvant led to a rapid innate immune cell
      response at the injection site, followed by the activation of natural killer and
      dendritic cells (DC) in regional draining lymph nodes. Strikingly, major
      histocompatibility complex (MHC) class I cross-presentation by CD8alpha(+) and
      CD8alpha(-) DCs was enhanced by up to 100-fold when antigen was formulated with
      ISCOMATRIX adjuvant. These coordinated features enabled efficient CD8(+) T-cell
      cross-priming, which exhibited prophylactic and therapeutic tumoricidal activity.
      The therapeutic efficacy of an ISCOMATRIX vaccine was further improved when co
      administered with an anti-CD40 agonist antibody, suggesting that ISCOMATRIX-based
      vaccines may combine favorably with other immune modifiers in clinical
      development to treat cancer. Finally, we identified a requirement for the myeloid
      differentiation primary response gene 88 (MyD88) adapter protein for both innate
      and adaptive immune responses to ISCOMATRIX vaccines in vivo. Taken together, our
      findings support the utility of the ISCOMATRIX adjuvant for use in the
      development of novel vaccines, particularly those requiring strong CD8(+) T-cell
      immune responses, such as therapeutic cancer vaccines.

PMID- 21894175
TI  - Bisphosphonate therapy in patients under androgen deprivation therapy for
      prostate cancer: a systematic review and meta-analysis.
AB  - The objective of this study was to clarify the role of bisphosphonates in the
      treatment of osteoporosis in patients with prostate adenocarcinoma under androgen
      deprivation therapy (ADT). The Medline, EMBASE, Cancerlit and the American
      Society of Clinical Oncology abstract databases were searched for published
      randomized, placebo-controlled trials evaluating the usage of bisphosphonates in
      patients with prostate cancer (PC) under ADT. The outcomes assessed were
      fracture, osteoporosis, incidence of adverse events and changes in bone mineral
      density (BMD) during treatment. A total of 15 articles (2634 participants) were
      included in the meta-analysis. Treatment with bisphosphonates showed a
      substantial effect in preventing fractures (risk ratio (RR), 0.80; P = 0.005) and
      osteoporosis (RR, 0.39; P <0.00001). Zoledronic acid showed the best number
      needed to treat (NTT), compared with placebo, in relation to fractures and
      osteoporosis (NNT = 14.9 and NNT = 2.68, respectively). The between-group
      difference (bisphosphonates vs placebo) in the lumbar spine and femoral neck BMD
      were 5.18 +/- 3.38% and 2.35 +/- 1.16%, respectively. This benefit of bone loss
      prevention could be reached without major side effects (cardiovascular or
      gastrointestinal events). Bisphosphonates are effective in preventing bone loss
      in patients with PC who are under ADT.

PMID- 21894176
TI  - The association of diabetes and positive prostate biopsy in a US veteran
      population.
AB  - BACKGROUND: Several studies have shown a protective effect of diabetes mellitus
      (DM) on incidence of prostate cancer; however, the data are not consistent.
      Moreover, whether or not DM is associated with a positive result among patients
      referred for prostate biopsy due to abnormal PSA and/or abnormal digital rectal
      examination is not clear. METHODS: A retrospective review of 3162 consecutive men
      who underwent prostate biopsy between January 2000 and July 2009 at the Atlanta
      Veterans Affairs Medical Center was performed. Men with positive and negative
      biopsies were compared for various demographic and clinical factors. The data
      were analyzed using logistic regression models with results expressed as adjusted
      odds ratios (ORs) with corresponding 95% confidence intervals (CI). RESULTS: DM
      was associated with increased odds of positive biopsy in the overall cohort (OR
      1.26, 95% CI: 1.01-1.55; P = 0.04). Subjects with DM had higher odds of more
      aggressive disease (Gleason >= 7) than those without the condition (OR 1.31, 95%
      CI: 0.98-1.74; P = 0.07). Race had no significant impact on these results.
      CONCLUSIONS: In this large series of prostate biopsies, diabetes is associated
      with higher odds of positive biopsy and higher Gleason grade. More studies
      investigating the role of DM and its associated comorbidities in prostate
      carcinogenesis are needed.

PMID- 21894177
TI  - Interventional cardiology: How should the appropriateness of PCI be judged?

PMID- 21894178
TI  - Atrial fibrillation: Strict rate control unnecessary in AF?

PMID- 21894179
TI  - Heart failure: Cardiac myosin activator shows promise in phase II trial.

PMID- 21894180
TI  - Prostate cancer: Unmeasured variables may confound the association between
      androgen deprivation therapy and cardiovascular risk.

PMID- 21894182
TI  - Mineral metabolism: High phosphate associated with renal disease progression.

PMID- 21894181
TI  - Hemodialysis in children with end-stage renal disease.
AB  - Although renal transplantation remains the most common treatment for children
      with end-stage renal disease (ESRD), the majority of children incident to ESRD
      receive dialytic therapy before receiving a renal allograft. Advances in the past
      decade have led to improved outcomes for children receiving maintenance
      hemodialysis, the majority of whom survive into adulthood. Medical, surgical,
      nutritional and psychosocial factors must be considered to provide optimal
      maintenance hemodialysis for children. In this Review, we discuss the various
      aspects of providing optimal hemodialysis to children, including vascular access,
      nutritional status, clearance targets, medications and assessment of health
      related quality of life.

PMID- 21894183
TI  - Anemia in children with chronic kidney disease.
AB  - Anemia is a common comorbidity in children with chronic kidney disease (CKD).
      This condition is associated with multiple adverse clinical consequences and its
      management is a core component of nephrology care. Increased morbidity and
      mortality, increased risk of cardiovascular disease and decreased quality of life
      have been associated with anemia of CKD in children. Although numerous complex
      factors interact in the development of this anemia, erythropoietin deficiency and
      iron dysregulation (including iron deficiency and iron-restricted erythropoiesis)
      are the primary causes. In addition to iron supplementation, erythropoietin
      stimulating agents (ESAs) can effectively treat this anemia, but there are
      important differences in ESA dose requirements between children and adults. Also,
      hyporesponsiveness to ESA therapy is a common problem in children with CKD.
      Although escalating ESA doses to target increased hemoglobin values in adults has
      been associated with adverse outcomes, no studies have demonstrated this
      association in children. The question of appropriate target hemoglobin levels in
      children, and the approach by which to achieve these levels, remains under
      debate. Randomized, controlled studies are needed to evaluate whether
      normalization of hemoglobin concentrations is beneficial to children, and whether
      this practice is associated with increased risks.

PMID- 21894184
TI  - Dialysis: Minocycline-EDTA lock reduces bacteremia in dialysis catheters.

PMID- 21894185
TI  - Critical care: estimating renal function in the ICU: even more challenging.

PMID- 21894187
TI  - Dialysis: Survival differences in patients on dialysis--not just black and white.

PMID- 21894189
TI  - Argonaute-2 regulates the proliferation of adult stem cells in planarian.

PMID- 21894190
TI  - FADD: an endogenous inhibitor of RIP3-driven regulated necrosis.

PMID- 21894191
TI  - Specific lectin biomarkers for isolation of human pluripotent stem cells
      identified through array-based glycomic analysis.
AB  - Rapid and dependable methods for isolating human pluripotent stem cell (hPSC)
      populations are urgently needed for quality control in basic research and in cell
      based therapy applications. Using lectin arrays, we analyzed glycoproteins
      extracted from 26 hPSC samples and 22 differentiated cell samples, and identified
      a small group of lectins with distinctive binding signatures that were sufficient
      to distinguish hPSCs from a variety of non-pluripotent cell types. These specific
      biomarkers were shared by all the 12 human embryonic stem cell and the 14 human
      induced pluripotent stem cell samples examined, regardless of the laboratory of
      origin, the culture conditions, the somatic cell type reprogrammed, or the
      reprogramming method used. We demonstrated a practical application of specific
      lectin binding by detecting hPSCs within a differentiated cell population with
      lectin-mediated staining followed by fluorescence microscopy and flow cytometry,
      and by enriching and purging viable hPSCs from mixed cell populations using
      lectin-mediated cell separation. Global gene expression analysis showed
      pluripotency-associated differential expression of specific fucosyltransferases
      and sialyltransferases, which may underlie these differences in protein
      glycosylation and lectin binding. Taken together, our results show that protein
      glycosylation differs considerably between pluripotent and non-pluripotent cells,
      and demonstrate that lectins may be used as biomarkers to monitor pluripotency in
      stem cell populations and for removal of viable hPSCs from mixed cell
      populations.

PMID- 21894192
TI  - A network-based gene-weighting approach for pathway analysis.
AB  - Classical algorithms aiming at identifying biological pathways significantly
      related to studying conditions frequently reduced pathways to gene sets, with an
      obvious ignorance of the constitutive non-equivalence of various genes within a
      defined pathway. We here designed a network-based method to determine such non
      equivalence in terms of gene weights. The gene weights determined are
      biologically consistent and robust to network perturbations. By integrating the
      gene weights into the classical gene set analysis, with a subsequent correction
      for the "over-counting" bias associated with multi-subunit proteins, we have
      developed a novel gene-weighed pathway analysis approach, as implemented in an R
      package called "Gene Associaqtion Network-based Pathway Analysis" (GANPA).
      Through analysis of several microarray datasets, including the p53 dataset,
      asthma dataset and three breast cancer datasets, we demonstrated that our
      approach is biologically reliable and reproducible, and therefore helpful for
      microarray data interpretation and hypothesis generation.

PMID- 21894188
TI  - Pharmacology, efficacy and safety of oral phosphate binders.
AB  - The ideal serum level of phosphate in patients on dialysis, and the benefits of
      controlling levels of phosphate in serum remain unclear despite observational
      studies that associate phosphate levels with mortality. In the absence of robust
      data from trials, current guidelines are necessarily based on opinion. Oral
      phosphate binders are required by the majority of patients on dialysis, and all
      of these binders can control serum levels of phosphate to similar degrees.
      Patient preference and adherence to prescribed therapy is at least as important
      as the efficacy of the prescribed binder. Avoidance of calcium-containing binders
      has become accepted practice where the alternatives are affordable, but
      incontrovertible evidence in favor of this approach is lacking. Use of sevelamer
      and lanthanum avoids calcium loading, but at considerable financial cost and with
      no reliable patient outcome data to prove their value. Additional approaches to
      aid control of serum levels of phosphate include blockade of gastrointestinal
      phosphate absorption and possibly binding of salivary phosphate. Importantly, the
      role of phosphate control in determining patient outcomes must be quantified,
      which is likely to require a large randomized, controlled study of two levels of
      phosphate control. Without such a study we will continue to rely on observational
      data with all its uncertainties and potential to mislead.

PMID- 21894194
TI  - IBD: Intestinal inflammation affected by density of enteric neurons.

PMID- 21894193
TI  - Arabidopsis phosphatidylinositol monophosphate 5-kinase 2 is involved in root
      gravitropism through regulation of polar auxin transport by affecting the cycling
      of PIN proteins.
AB  - Phosphatidylinositol monophosphate 5-kinase (PIP5K) catalyzes the synthesis of PI
      4,5-bisphosphate (PtdIns(4,5)P(2)) by phosphorylation of PI-4-phosphate at the 5
      position of the inositol ring, and is involved in regulating multiple
      developmental processes and stress responses. We here report on the functional
      characterization of Arabidopsis PIP5K2, which is expressed during lateral root
      initiation and elongation, and whose expression is enhanced by exogenous auxin.
      The knockout mutant pip5k2 shows reduced lateral root formation, which could be
      recovered with exogenous auxin, and interestingly, delayed root gravity response
      that could not be recovered with exogenous auxin. Crossing with the DR5-GUS
      marker line and measurement of free IAA content confirmed the reduced auxin
      accumulation in pip5k2. In addition, analysis using the membrane-selective dye
      FM4-64 revealed the decelerated vesicle trafficking caused by PtdIns(4,5)P(2)
      reduction, which hence results in suppressed cycling of PIN proteins (PIN2 and
      3), and delayed redistribution of PIN2 and auxin under gravistimulation in pip5k2
      roots. On the contrary, PtdIns(4,5)P(2) significantly enhanced the vesicle
      trafficking and cycling of PIN proteins. These results demonstrate that PIP5K2 is
      involved in regulating lateral root formation and root gravity response, and
      reveal a critical role of PIP5K2/PtdIns(4,5)P(2) in root development through
      regulation of PIN proteins, providing direct evidence of crosstalk between the
      phosphatidylinositol signaling pathway and auxin response, and new insights into
      the control of polar auxin transport.

PMID- 21894195
TI  - Surgery: Fast-track colonic surgery and the 'knowing-doing' gap.

PMID- 21894196
TI  - New imaging techniques and opportunities in endoscopy.
AB  - Gastrointestinal endoscopy is undergoing major improvements, which are driven by
      new available technologies and substantial refinements of optical features. In
      this Review, we summarize available and evolving imaging technologies that could
      influence the clinical algorithm of endoscopic diagnosis. Detection,
      characterization and confirmation are essential steps required for proper
      endoscopic diagnosis. Optical and nonoptical methods can help to improve each
      step; these improvements are likely to increase the detection rate of neoplasias
      and reduce unnecessary endoscopic treatments. Furthermore, functional and
      molecular imaging are emerging as new diagnostic tools that could provide an
      opportunity for personalized medicine, in which endoscopy will define disease
      outcome or predict the response to targeted therapy.

PMID- 21894198
TI  - IBD: Regular, prolonged aspirin use and an increased risk of Crohn's disease.

PMID- 21894197
TI  - Phytochemicals and colorectal cancer prevention--myth or reality?
AB  - Chemoprevention of colorectal cancer has been the focus of intensive research for
      more than two decades. Epidemiological evidence has shown a small, but
      significant association between fruit and vegetable intake and a reduction in
      colorectal cancer risk. In vitro and animal data have also demonstrated that many
      dietary phytochemicals have potent chemopreventive activities. However, in
      humans, single-agent compounds have yielded conflicting results. A key concept is
      that dietary phytochemicals exert beneficial effects at low concentrations when
      working in synergy with each other. As the gut microflora evolved in an
      environment rich in dietary fiber and phytochemicals, the rapid shift towards a
      Western diet creates an environment in which the gut is more vulnerable to
      carcinogens, genetic alterations and inflammation. As enforcing dietary
      interventions on large populations is not realistic, we believe future
      chemopreventive work should focus on delivering phytochemical mixtures that
      target the multiple molecular events involved in colorectal carcinogenesis.

PMID- 21894199
TI  - Critical analysis of hot topics in NOTES.
AB  - Natural orifice transluminal endoscopic surgery (NOTES) has gained a great deal
      of attention from gastroenterologists and surgeons all over the world since its
      introduction in 2000. The field of NOTES has advanced tremendously since that
      time and exciting and well-designed research has been reported. Both randomized
      controlled trials and results from large national and international registries
      have been published. Many experimental and clinical studies have discussed
      transesophageal, transgastric, transvaginal and transrectal access for a variety
      of NOTES procedures. Transvaginal access has been the most frequently reported
      NOTES access route in clinical trials. When suitable instruments become
      available, a true comparison of NOTES with current laparoscopic approaches can be
      realized.

PMID- 21894200
TI  - Benign biliary strictures: current endoscopic management.
AB  - Endoscopic treatment is the mainstay of therapy for benign billiary strictures,
      and surgery is reserved for selected patients in whom endoscopic treatment fails
      or is not feasible. The endoscopic approach depends mainly on stricture etiology
      and location, and generally involves the placement of one or multiple plastic
      stents, dilation of the stricture(s), or a combination of these approaches.
      Knowledge of biliary anatomy, endoscopy experience and a well-equipped endoscopy
      unit are necessary for the success of endoscopic treatment. This Review discusses
      the etiologies of benign biliary strictures and different endoscopic therapies
      and their respective outcomes. Data on newer therapies, such as the placement of
      self-expandable metal stents, and the treatment of biliary-enteric anastomotic
      strictures is also reviewed.

PMID- 21894201
TI  - Endoscopic management of Barrett esophagus.
AB  - Endoscopy has a vital role in the diagnosis, screening, surveillance and
      treatment of Barrett esophagus. Over the past few decades, tremendous advances
      have been made in endoscopic technology, and the management of dysplasia and
      early cancer in Barrett esophagus has changed radically from being surgical to
      organ-sparing endoscopic therapy. Proper endoscopic techniques and systematic
      biopsy protocols improve dysplasia detection, and endoscopic surveillance
      improves outcomes in patients with Barrett esophagus and dysplasia. Endoscopic
      treatment can be tissue acquiring (as in endoscopic mucosal resection and
      endoscopic submucosal dissection) or ablative (as with photodynamic therapy,
      radiofrequency ablation and cryotherapy). Treatment is usually multimodal,
      combining endoscopic resection of visible lesions with one or more mucosal
      ablation techniques, followed by long-term surveillance. Such treatment is safe
      and effective. Shared decision-making between the patient and physician is
      important while considering treatment for dysplasia in Barrett esophagus. Issues
      such as durability of response, importance of subsquamous Barrett epithelium and
      the optimal management strategy in patients with low-grade dysplasia and
      nondysplastic Barrett esophagus need to be studied further. Development of safer
      wide-field resection techniques, which would effectively remove all Barrett
      esophagus and obviate the need for long-term surveillance, is needed.

PMID- 21894203
TI  - Liver: Targeted gene silencing could prevent liver ischemia-reperfusion injury.

PMID- 21894202
TI  - Colonoscopy: basic principles and novel techniques.
AB  - Colonoscopy is considered the 'gold standard' for detection and removal of
      premalignant lesions in the colon. However, studies suggest that colonoscopy is
      less protective for right-sided than for left-sided colorectal cancer. Optimizing
      the effectiveness of colonoscopy is a continuous process, and during the past
      decade several important quality indicators have been defined that can be used to
      measure the performance of colonoscopy and to identify areas for quality
      improvement. The quality of bowel preparation can be enhanced by split-dose
      regimens, which are superior to single-dose regimens. Cecal intubation rates
      should approximate 95% and can be optimized by good technique. In selected
      patients, specific devices can be used to facilitate cecal intubation. Adenoma
      detection rates should be monitored and exceed a minimum of 25% in men and 15% in
      women. To this aim, optimal withdrawal technique and adequate time for inspection
      are of utmost importance. Of all advanced imaging techniques, chromoendoscopy is
      the only technique with proven benefit for adenoma detection. Finally, the
      technique of polypectomy affects the number of complications as well as the
      success of completely removing a lesion. In this Review, we provide an overview
      of both standard and novel colonoscopy techniques and their impact on quality
      indicators.

PMID- 21894205
TI  - Chemotherapy: Advanced Hodgkin lymphoma--balancing toxicity and cure.

PMID- 21894206
TI  - Chemotherapy: Cisplatin more effective when given less often.

PMID- 21894207
TI  - Targeted therapies: Should we be aghast at the AVAGAST data?

PMID- 21894208
TI  - Do autoantibodies to C3 exacerbate autoimmunity in SLE?

PMID- 21894209
TI  - IL-20 blockade to block bone loss?

PMID- 21894211
TI  - Epilepsy: extract from human stem cells shows promise in mouse model of epilepsy.

PMID- 21894210
TI  - Mediators of the inflammatory response to joint replacement devices.
AB  - Joint replacement surgery is one of the success stories of modern medicine,
      restoring mobility, diminishing pain and improving the overall quality of life
      for millions of people. Unfortunately, wear of these prostheses over time
      generates debris, which activates an innate immune response that can ultimately
      lead to periprosthetic resorption of bone (osteolysis) and failure of the
      implant. Over the past decade, the biological interactions between the
      particulate debris from various implant materials and the immune system have
      begun to be better understood. The wear debris induces a multifaceted immune
      response encompassing the generation of reactive oxygen species and damage
      associated molecular patterns, Toll-like receptor signaling and NALP3
      inflammasome activation. Acting alone or in concert, these events generate
      chronic inflammation, periprosthetic bone loss and decreased osteointegration
      that ultimately leads to implant failure.

PMID- 21894213
TI  - Diabetes: brain, mind, insulin--what is normal and do we need to know?

PMID- 21894212
TI  - Cholesterol metabolism in Huntington disease.
AB  - The CNS is rich in cholesterol, which is essential for neuronal development and
      survival, synapse maturation, and optimal synaptic activity. Alterations in brain
      cholesterol homeostasis are linked to neurodegeneration. Studies have
      demonstrated that Huntington disease (HD), a progressive and fatal
      neurodegenerative disorder resulting from polyglutamine expansion in the
      huntingtin protein, is associated with changes in cellular cholesterol
      metabolism. Emerging evidence from human and animal studies indicates that
      attenuated brain sterol synthesis and accumulation of cholesterol in neuronal
      membranes represent two distinct mechanisms occurring in the presence of mutant
      huntingtin that influence neuronal survival. Increased knowledge of how changes
      in intraneuronal cholesterol metabolism influence the pathogenesis of HD will
      provide insights into the potential application of brain cholesterol regulation
      as a therapeutic strategy for this devastating disease.

PMID- 21894217
TI  - A new twist in actin filament nucleation.

PMID- 21894214
TI  - Antiresorptive therapies for osteoporosis: a clinical overview.
AB  - Antiresorptive therapies are used to increase bone strength in individuals with
      osteoporosis and include five principal classes of agents: bisphosphonates,
      estrogens, selective estrogen receptor modulators (SERMs), calcitonin and
      monoclonal antibodies such as denosumab. However, no head-to-head studies have
      compared different antiresorptive agents using fracture as an end point.
      Bisphosphonates, which have proven antifracture efficacy and a good safety
      profile, are the most widely used first-line antiresorptive therapy and are
      recommended for patients with osteoporosis, a prior fragility fracture or
      osteopenia, as well as individuals with a high risk of fracture. Denosumab, which
      also has good antifracture efficacy, is another possible first-line therapy,
      although long-term safety data are lacking. However, no single antiresorptive
      therapy is currently appropriate for all patients or clearly superior to other
      therapies. Antiresorptive agents such as estrogens, SERMs (in postmenopausal
      women) and calcitonin are considered to be second-line agents that are
      appropriate in special circumstances. Clinicians should determine the most
      appropriate pharmacological therapy after a careful assessment of the
      risk:benefit profiles of these drugs in each patient. In addition, patients
      should receive a detailed explanation of the treatment goals, so that the
      therapeutic benefit can be maximized through good compliance and persistence.

PMID- 21894215
TI  - A patient with a large recurrent pheochromocytoma demonstrating the pitfalls of
      diagnosis.
AB  - BACKGROUND: A 59-year-old man presented for a follow-up, 6 years after surgery
      for a large pheochromocytoma. He had suffered from diabetes mellitus,
      hypertension and abdominal pain in the right flank region. Previous postoperative
      follow-up did not reveal tumor recurrence. INVESTIGATION: Measurement of plasma
      free metanephrine and normetanephrine by high-performance liquid chromatography
      and radioimmunoassay; 123I-metaiodobenzylguanidine (MIBG) scintigraphy; hybrid
      123I-MIBG single-photon emission CT (SPECT)-CT; MRI; testing for plasma
      norepinephrine and epinephrine; intraoperative ultrasonography; histological
      staining for chromogranin A and synaptophysin; and postoperative 18F
      dihydroxyphenylalanine (DOPA) PET scan. DIAGNOSIS: Recurrent pheochromocytoma.
      MANAGEMENT: Laparotomy with tumor resection. Reduction of antihypertensive
      medications. Further follow-up by MRI, hybrid 123I-MIBG SPECT-CT and testing for
      plasma catecholamines and free metanephrines.

PMID- 21894225
TI  - Gastroesophageal reflux symptoms and comorbid asthma and posttraumatic stress
      disorder following the 9/11 terrorist attacks on World Trade Center in New York
      City.
AB  - OBJECTIVES: Excess gastroesophageal reflux disease (GERD) was reported in several
      populations exposed to the September 11 2001 (9/11) terrorist attacks on the
      World Trade Center (WTC). We examined new onset gastroesophageal reflux symptoms
      (GERS) since 9/11 and persisting up to 5-6 years in relation to 9/11-related
      exposures among the WTC Health Registry enrollees, and potential associations
      with comorbid asthma and posttraumatic stress disorder (PTSD). METHODS: This is a
      retrospective analysis of 37,118 adult enrollees (i.e., rescue/recovery workers,
      local residents, area workers, and passersby in lower Manhattan on 9/11) who
      reported no pre-9/11 GERS and who participated in two Registry surveys 2-3 and 5
      6 years after 9/11. Post-9/11 GERS (new onset since 9/11) reported at first
      survey, and persistent GERS (post-9/11 GERS reported at both surveys) were
      analyzed using log-binomial regression. RESULTS: Cumulative incidence was 20% for
      post-9/11 GERS and 13% for persistent GERS. Persistent GERS occurred more often
      among those with comorbid PTSD (24%), asthma (13%), or both (36%) compared with
      neither of the comorbid conditions (8%). Among enrollees with neither asthma nor
      PTSD, the adjusted risk ratio (aRR) for persistent GERS was elevated among:
      workers arriving at the WTC pile on 9/11 (aRR=1.6; 95% confidence interval (CI)
      1.3-2.1) or working at the WTC site > 90 days (aRR=1.6; 1.4-2.0); residents
      exposed to the intense dust cloud on 9/11 (aRR=1.5; 1.0-2.3), or who did not
      evacuate their homes (aRR=1.7; 1.2-2.3); and area workers exposed to the intense
      dust cloud (aRR=1.5; 1.2-1.8). CONCLUSIONS: Disaster-related environmental
      exposures may contribute to the development of GERS. GERS may be accentuated in
      the presence of asthma or PTSD.

PMID- 21894226
TI  - Once-daily dosing vs. conventional dosing schedule of mesalamine and relapse of
      quiescent ulcerative colitis: systematic review and meta-analysis.
AB  - OBJECTIVES: Maintenance therapy with 5-aminosalicylates (5-ASAs) is recommended
      in patients with quiescent ulcerative colitis (UC), but compliance rates are low.
      Once-daily dosing may improve adherence, but impact on the relapse of disease
      activity is unclear as no previous meta-analysis has studied this issue. METHODS:
      MEDLINE, EMBASE, and the Cochrane central register of controlled trials were
      searched (through April 2011). Eligible randomized controlled trials (RCTs)
      recruited adults with quiescent UC, and compared once-daily dosing of 5-ASAs with
      a more frequent dosing schedule of an identical total daily dose of the same 5
      ASA drug. Minimum treatment duration was 6 months. Trials reported a dichotomous
      assessment of relapse of disease activity at last point of follow-up. Data
      concerning non-compliance and adverse events were extracted, where reported.
      Effect of once-daily vs. more frequent dosing schedule was reported as relative
      risk (RR) of relapse with a 95% confidence interval (CI). RESULTS: The search
      identified 3,061 citations, and seven RCTs containing 2,745 patients were
      eligible. All RCTs used mesalamine. Relapse rates were not significantly
      different between once-daily and conventional dosing schedules for mesalamine (RR
      of relapse=0.94; 95% CI: 0.82-1.08). Non-compliance (RR=0.87; 95% CI: 0.46-1.66)
      and adverse events were no more likely with once-daily dosing (RR=1.08; 95% CI:
      0.97-1.20). CONCLUSIONS: Once-daily dosing with mesalamine is as effective as
      conventional dosing schedules for the prevention of relapse of quiescent UC,
      although there is no definitive evidence that compliance with once-daily dosing
      is better. Adverse events occur at a similar frequency.

PMID- 21894227
TI  - [Skin tags and Acanthosis nigricans: association with insulin resistance and
      overweight in Mexican children].
AB  - BACKGROUND: Childhood overweight and obesity are a notorious health problem
      around the world that may lead to an increase in insulin resistance and metabolic
      syndrome. Acanthosis nigricans (AC) and skin tags (ST) are skin markers that can
      help to obtain an early diagnose of these metabolic disorders. OBJECTIVE: To
      determine whether such skinmarkers (ST and AN), correlate with insulin resistance
      based on the assessment of the homeostasis model of insulin resistance (HOMA-IR),
      and also with overweight and obesity. METHODS: Weight, height and body mass index
      were obtained and accordingly to CDC based on percentiles, and classification was
      made as follows: underweight, healthy weight, overweight and obesity. Beside
      insulin, glucose, and HOMA-IR were assessed. RESULTS: We included 186 patients
      age range 6-14 yr, 89 female, 97 male, 10 with underweight, 148 healthy weight,
      18 overweight, 10 obese; 18 children presented ST and 29 AN. We found a
      relationship between the presence of ST and AN with higher BMI and insulin
      resistance. CONCLUSIONS: The presence of skin tags and Acanthosis nigricans
      correlates with the presence of insulin resistance in children even in healthy
      weight patients and higher BMI.

PMID- 21894228
TI  - [Estimating the incidence of 2009 pandemic influenza A(H1N1) among IMSS
      affiliates].
AB  - INTRODUCTION: The purpose of this study is to estimate the burden of the disease
      associated to pandemic 2009 influenza virus, from April 2009 to January 2010.
      METHODS: To estimate the number of symptomatic cases, the number of
      hospitalizations and deaths we used the Center for Disease Control (CDC)
      recommended method that takes into account the underestimation associated with
      the use of health services, the practices of confirmation and registration of
      cases.To estimate the incidence of infection, we applied the recently reported
      London sero-incidence by age group to the IMSS population. RESULTS: Each case of
      symptomatic confirmed influenza represented 51 cases during the first wave and 18
      in the second wave. We estimate 537,167 (range 378,439-813,008) symptomatic
      cases. Each confirmed hospitalized person represented 2.2 cases. The estimate of
      hospitalizations was 10,063 (range 7,441-14,610). The ratio of hospitalization to
      the total number of cases was 1.8%. The estimated incidence of infection was
      close to 24%. CONCLUSIONS: Confirmed cases in the epidemiological surveillance
      system are only a small proportion of the population infected and symptomatic
      cases, information relevant in planning new outbreaks.

PMID- 21894229
TI  - [Knowledge and practices on toxoplasmosis in physicians attending pregnant women
      in Durango, Mexico].
AB  - OBJECTIVES: To determine the level of knowledge and practices about toxoplasmosis
      in physicians attending pregnant women in Durango, Mexico. MATERIALS AND METHODS:
      One hundred physicians attending pregnant women in Durango,Mexico were surveyed.
      Of them, 67 were general practitioners, 17 family physicians, and 16
      obstetricians. They were asked about (i) the parasite Toxoplasma gondii; (ii)
      general aspects about toxoplasmosis including clinical manifestations,diagnosis,
      treatment, and epidemiology; and (iii) their practices and experiences on
      toxoplasmosis. RESULTS: From 66 to 89% (mean 78.5%) of physicians answered
      correctly about the parasite; 25 to 63% (mean 46.9%) answered correctly about
      clinical manifestations; and 36 to 45% (mean 40.5%) answered correctly about the
      serological diagnosis. Only 7% knew about the use of avidity test. Few physicians
      (23%) knew what medicaments are used against toxoplasmosis.From 12 to 86% (mean
      40.3%) of participants answered correctly about transmission routes and only 7%
      got the right answer about susceptibility of infection. Fifty-nine percent of
      physicians never requested laboratory tests for detecting toxoplasmosis, and only
      31% provide information for preventing infection to all their patients. Sixteen
      (16%) physicians had detected at least one case of Toxoplasma infection acquired
      during pregnancy. CONCLUSIONS: The physicians surveyed showed an incomplete
      knowledge about diagnosis and treatment of toxoplasmosis. Results are useful for
      optimal design of strategies in the medical education about toxoplasmosis.

PMID- 21894230
TI  - [Prevalence of bacterial infections and patterns of bacterial susceptibility
      among patients with fever, neutropenia, and hematological neoplasias].
AB  - Chemotherapy induces immunosuppression which is associated with a significant
      increase in the frequency and severity of infections. Neutropenia is the most
      important factor in determining susceptibility to bacterial infections. Our aim
      was to establish the prevalence of bacterial infections and bacterial
      susceptibility patterns in patients with fever, neutropenia and hematological
      neoplasias. Cultures were obtained prior empirical antimicrobial treatment.
      Susceptibility tests to antibiotics were performed for all microorganisms
      considered pathogens. Descriptive statistics were used for each variable.
      Differences between proportions were estimated by means of chi2 or Fisher's exact
      test. We included 85 patients.Primary bacteremia was the most frequent cause of
      fever (52%). Microorganisms most frequently isolated were:S. epidermidis (54.2%),
      E. coli (12.5%), S. aureus (8.3%). In susceptibility tests 88.5% of S.
      epidermidis strains were resistant to oxaciline (MIC > 8 MU/ml); E. coli was
      resistant to ceftazidime (50%) and trimethroprim/sulfamethoxazole (83%).In
      conclusion, gram-positive microorganisms are predominant in patients with fever
      and neutropenia followed by gram-negatives like E. coli. Predominance of gram
      positives microorganism forces us to reconsider our current prophylactic and
      therapeutic antimicrobials regimens used in these patients.

PMID- 21894231
TI  - [Principles and technique of magnetic resonance guided focused ultrasound surgery
      (MRgFUS) in the treatment of uterine fibroids].
AB  - Uterine fibroids are a significant source of morbidity for women of reproductive
      age, and can result in substantial symptoms affecting their quality of life.
      Definitive treatment has traditionally been a myomectomy, but increasingly women
      are not prepared to undergo such an invasive procedure for a benign and usually
      self-limiting condition. Focused ultrasound ablation is one of the least invasive
      treatment options outside medical therapy and does not require an
      anesthetic.Magnetic resonance guided focused ultrasound (MRgFUS) ablation
      combines therapy delivered by an ultrasound transducer with imaging guidance for
      therapy and thermal feedback provided by magnetic resonance imaging. This paper
      provides an overview of the MRgFUS technique, including a brief description of
      the treatment system, guidelines for selection of patients and follow-up, and a
      comparison with other treatment techniques.

PMID- 21894232
TI  - [Pioneers of Mexican thoracic surgery].
AB  - The development of thoracic surgery as a specialty is linked to the acquisition
      of knowledge and skills such as the resolution of the open pneumothorax with
      differential pressure and tracheal intubation, asepsis, antibiotic therapy and
      intensive care.Our pioneers in thoracic development were general surgeons who
      ventured into this field during the late nineteenth and early twentieth
      centuries, culminating in the transition to a full blown specialty during the
      second half of the 20th century.

PMID- 21894233
TI  - [Phosphine poisoning in healthcare workers].
AB  - Phosphine gas constitutes a potential and serious little-known cause of poisoning
      of professional nature of the medical staff and nursing care of patients who
      voluntarily swallow phosphides rodenticides purposes suicide. The objective of
      this paper is to inform to healthcare workers from urgencies, forensic and
      occupational health services on this occupational hazard. We present the case of
      a nurse who suffered from poisoning by gas phosphine confirmed through an
      environmental monitoring of gases in an emergency department carried out by the
      government service of civil protection of the State of Jalisco.

PMID- 21894234
TI  - [Severe sepsis, septic shock and secondary multiple organ dysfunction in
      infection by Kluyvera ascorbata].
AB  - Kluyvera, a new genus of Enterobacteriaceae, is an emergent pathogen. Kluyvera
      species have been isolated from sputum, urine, stools, and blood. Kluyvera
      strains are infrequent but potentially dangerous pathogens in the immunocompetent
      or immunocompromised host due to their potential to provoke a wide range of
      infections and their ability to transfer extended spectrum beta lactamase genes.
      We herein report the case of a teenage male with severe sepsis and septic shock
      due to K. ascorbata.

PMID- 21894235
TI  - [Breast metastasis from a colonic adenocarcinoma: a case report and literature
      review].
AB  - Metastasis to the breast from extramammary tumors are uncommon and metastatic
      colon carcinoma (MCC) to the breast is extremely rare. A case history is
      presented of a 42 year-old woman with a finding of a breast lump. One year
      before,she had undergone an anterior colon resection for a rectal carcinoma.
      Mammographic examination revealed a high density, well demarcated, 3 cm lesion
      located in the upper outer quadrant of left breast, along with smaller multiple
      bilateral nodules. Following breast biopsy, the final diagnosis of MCC was based
      on the absence of any precursor lesion within the breast (no surrounding ductal
      carcinoma in situ) and of the expression of cytokeratin 20 and beta-catenin on
      immunohistochemistry.The treatment strategy for metastatic breast disease is
      based on a proper assessment of such cases by surgeons,radiologists and
      pathologists.

PMID- 21894236
TI  - [Epilepsy as a cause of removal from the Armed Forces].
AB  - Recently, the First Chamber of the Supreme Court of Justice decided two important
      cases where the Ministers were urged to evaluate whether a provision of the
      Social Security Institute for the Mexican Armed Forces Statute making"epilepsy
      and other forms of seizures or equivalents" a cause of removal from the Army on
      the basis of "uselessness in the service" violates the equality and non
      discrimination principle laid down in article 1 of the Federal Constitution. Four
      Supreme Court Ministers declared that the provision was constitutional. Justice
      Minister Cossio Diaz disagreed and wrote a separate opinion where he holds that
      the aforementioned provision is unconstitutional, since its excessively wide and
      undetermined language opens the door to declarations of "uselessness for the
      service" without ensuring this rests in every case in a genuine incapacity to
      develop a job in the Army.Before reaching this conclusion Justice Minister Cossio
      asked for information to the National Institute of Neurology and Neurosurgery. It
      was on these basis that he sustained that the aforementioned legal provision does
      not satisfy an adequate means-end correlation, since it allows the Army to
      withdraw from service -on the basis of "uselessness"-persons whose medical
      condition is sometimes episodic; others curable; others, if not curable,
      pharmaceutically controlled; and, in cases where it does limit the kinds of
      activity, that the person can develop, it does so in a way that can only be
      determined by an intensely individualized basis.

PMID- 21894237
TI  - A theory-based approach to teaching young children about health: A recipe for
      understanding.
AB  - The theory-theory account of conceptual development posits that children's
      concepts are integrated into theories. Concept learning studies have documented
      the central role that theories play in children's learning of experimenter
      defined categories, but have yet to extensively examine complex, real-world
      concepts such as health. The present study examined whether providing young
      children with coherent and causally-related information in a theory-based lesson
      would facilitate their learning about the concept of health. This study used a
      pre-test/lesson/post-test design, plus a five month follow-up. Children were
      randomly assigned to one of three conditions: theory (i.e., 20 children received
      a theory-based lesson); nontheory (i.e., 20 children received a nontheory-based
      lesson); and control (i.e., 20 children received no lesson). Overall, the results
      showed that children in the theory condition had a more accurate conception of
      health than children in the nontheory and control conditions, suggesting the
      importance of theories in children's learning of complex, real-world concepts.

PMID- 21894238
TI  - A simple and efficient route to the FKBP-binding domain from rapamycin.
AB  - A simple and highly efficient route to the FKBP-binding domain (FKBD) from the
      natural product rapamycin has been developed, which entails a sequence of
      ozonolysis/Baeyer-Villiger/Wittig reactions. The newly synthesized FKBD may serve
      as a core to assemble hybrid macrocyclic libraries for the discovery of novel
      probes of protein function and to synthesize new ligands for the FKBP family of
      proteins.

PMID- 21894239
TI  - Achieving Safety: Safer Sex, Communication, and Desire among Young Gay Men.
AB  - Conceptualizations of safer sex practices among young gay men (YGM) are
      frequently structured around communication between partners and the subsequent
      utilization or absence of condoms in a sexual encounter. Drawing on a sample of
      34 in-depth interviews with YGM, ages 18 to 24, we explore the ways in which
      conceptualizations and definitions of safer sex are discussed and enacted.
      Placing attention on their safer sex practices, we analyze the conversations that
      do and do not occur among YGM and their partners, including the strategies (e.g.,
      negotiated safety, condom communication and negotiation) that are commonly
      perceived as most useful by YGM. We provide recommendations regarding how to
      craft safer sex messages for YGM by considering their competing demands.

PMID- 21894240
TI  - Photolithography of Dithiocarbamate-Anchored Monolayers and Polymers on Gold.
AB  - Dithiocarbamate (DTC)-anchored monolayers and polymers were investigated as
      positive resists for UV photolithography on planar and roughened Au surfaces.
      DTCs were formed in situ by the condensation of CS(2) with monovalent or
      polyvalent amines such as linear polyethyleneimine (PEI) under mildly basic
      aqueous conditions, just prior to surface passivation. The robust adsorption of
      the polyvalent PEI-DTC to Au surfaces supported high levels of resistance to
      photoablation, providing opportunities to generate thin films with gradient
      functionality. Treatment of photopatterned substrates with alkanethiols produced
      binary coatings, enabling a direct visual comparison of DTC- and thiol-passivated
      surfaces against chemically induced corrosion using confocal microscopy.

PMID- 21894241
TI  - Estimation and Variable Selection for Semiparametric Additive Partial Linear
      Models (SS-09-140).
AB  - Semiparametric additive partial linear models, containing both linear and
      nonlinear additive components, are more flexible compared to linear models, and
      they are more efficient compared to general nonparametric regression models
      because they reduce the problem known as "curse of dimensionality". In this
      paper, we propose a new estimation approach for these models, in which we use
      polynomial splines to approximate the additive nonparametric components and we
      derive the asymptotic normality for the resulting estimators of the parameters.
      We also develop a variable selection procedure to identify significant linear
      components using the smoothly clipped absolute deviation penalty (SCAD), and we
      show that the SCAD-based estimators of non-zero linear components have an oracle
      property. Simulations are performed to examine the performance of our approach as
      compared to several other variable selection methods such as the Bayesian
      Information Criterion and Least Absolute Shrinkage and Selection Operator
      (LASSO). The proposed approach is also applied to real data from a nutritional
      epidemiology study, in which we explore the relationship between plasma beta
      carotene levels and personal characteristics (e.g., age, gender, body mass index
      (BMI), etc.) as well as dietary factors (e.g., alcohol consumption, smoking
      status, intake of cholesterol, etc.).

PMID- 21894242
TI  - Synthesis and characterization of novel fluorescent nitrogen-containing
      bisphosphonate imaging probes for bone active drugs.
AB  - Progress in the synthesis of novel fluorescent conjugates of N-heterocyclic
      bisphosphonate drugs and related analogues, together with some recent
      applications of these compounds as imaging probes, are briefly discussed.

PMID- 21894243
TI  - Nonmarital Fertility, Family Structure, and the Early School Achievement of Young
      Children from Different Race/Ethnic and Immigration Groups.
AB  - Working from a life course perspective, this study examined the links between
      mothers' fertility and relationship statuses and children's early school
      achievement and how these links varied by race/ethnicity and immigration status.
      Analyses of nationally representative data from the Early Childhood Longitudinal
      Study-Kindergarten Cohort revealed that children born to unmarried women scored
      lower than children of married women on math tests in kindergarten and first
      grade. This pattern was most attributable to associated differences in family
      income and parent education, and it was moderated by women's marital and
      relationship statuses after having their children. Evidence also suggested that
      the academic risks of some family structure pattern relative to continuously
      married parents might have been more pronounced for White children.

PMID- 21894244
TI  - mTOR inhibitors in renal cell carcinoma.
AB  - The mammalian target of rapamycin (mTOR) is a downstream effector of the PI3
      K/Akt/mTOR pathway. Allosteric inhibitors of mTOR, everolimus and temsirolimus,
      have shown promising clinical activity in advanced renal cell carcinoma but their
      effect is far from durable and only a subset of patients experience substantial
      benefit from these agents. The PI3-K/Akt/mTOR pathway represents an intricate
      network of fine regulation and feedback loops, and resistance to allosteric mTOR
      inhibitors may be embedded within this complexity. In this article we highlight
      the molecular elements of the PI3-K/Akt/mTOR pathway, the clinical experience
      with everolimus and temsirolimus in advanced renal cell carcinoma, and the future
      directions in terms of sequential therapy, combinational therapy and development
      of novel therapeutic agents.

PMID- 21894245
TI  - Diagnosis of cerebral cortical vein thrombosis with T2* weighted magnetic
      resonance imaging.
AB  - A 47-year-old woman presented with paresthesia in her left arm and trunk. She was
      diagnosed as having an arterial pure sensory stroke at first presentation. On the
      second hospital day, left hemiparesis developed after convulsions. Magnetic
      resonance (MR) imaging revealed a hyperintense lesion involving the right
      parietal lobe on diffusion weighted image. The T2* weighted image disclosed a
      linear hypointense lesion in the same area. Progressive feature of her symptoms
      and T2* weighted MR image prompted us to perform MR venography. MR venography
      confirmed the diagnosis of cortical vein and sagittal sinus thrombosis. Her
      symptoms attenuated gradually after anticoagulation therapy. Gene analysis showed
      type I anti-thrombin III (ATIII) deficiency due to the novel mutation of AT III
      gene. T2* weighted imaging may be much more sensitive than other imaging to
      detect thrombosed cortical vein during the first week after onset. Rapid
      diagnosis induced appropriate treatment and monitoring of the patient.

PMID- 21894246
TI  - Infectious mononucleosis with secondary cold agglutinin disease causing
      autoimmune haemolytic anaemia.
AB  - This case report describes a 20-year-old woman whose initial clinical,
      laboratory, and radiological presentation suggested obstructive jaundice.
      However, she was subsequently found to be suffering from autoimmune haemolytic
      anaemia resulting from an Epstein-Barr virus infection complicated by cold
      agglutinin disease. The patient went on to make a complete clinical recovery
      after discharge.

PMID- 21894247
TI  - Thyrotoxic hypokalaemic periodic paralysis in a man from Nepal.
AB  - A case is presented of a rare complication of hyperthyroidism, known as
      thyrotoxic hypokalaemic periodic paralysis, in a man from Nepal. A 26-year-old
      Nepalese man, with known hypokalaemia, was referred to the clinical laboratory
      services for electrolyte analysis. Results showed Na(+) 120 mmol/l and K(+) 2.8
      mmol/l, and he was prescribed potassium chloride. In fact, he had previously been
      receiving potassium supplementation periodically and his history revealed that he
      had experienced the same type of attack and was hospitalised 6 months earlier. He
      had profound tremor and was agitated and irritable during his visit to this
      hospital. Thyroid function testing showed high T3 (tri-iodothyronine) and T4
      (thyroxine) with low thyroid stimulating hormone (TSH) concentration in the
      serum, indicating thyrotoxic hypokalaemic periodic paralysis. Treatment with
      neomercazole resulted in an improvement during the follow up visit. Hypokalaemia
      is believed to be a consequence of a massive shift due to increased sodium
      potassium-adenosine triphosphatase (Na(+)K(+)ATPase ) pump activity in the
      presence of elevated thyroid hormones.

PMID- 21894248
TI  - Sudden cardiac arrest in apical hypertrophic cardiomyopathy.
AB  - We present two cases of cardiac arrest, presumably attributable to apical
      hypertrophic cardiomyopathy(HCM). The first case was a 37-year-old Asian man
      known to have an apical HCM and was successfully resuscitated from an "out of
      hospital" ventricular fibrillation arrest. He underwent an electrophysiological
      study that was unable to induce tachyarrhythmias, which may not be surprising. He
      did receive an automated internal cardioverter defibrillator (AICD) in compliance
      with his class I indication for an implantable defibrillator. The second patient
      was an 86-year-old Caucasian woman with a cardiac history significant for apical
      HCM, coronary artery disease, diastolic heart failure, and monomorphic
      ventricular tachycardia. She underwent electrophysiological testing for frequent
      dizziness and monomorphic ventricular tachycardia of a right ventricular origin
      was induced. She received an AICD for sudden cardiac death prevention. Though
      lethal ventricular arrhythmias have been reported in patients with apical HCM,
      the prevailing consensus is that the prognosis of apical HCM is benign. Whether
      these accounts are truly exceptional occurrences for this rare and conventionally
      regarded benign condition or whether they represent an under-appreciated risk for
      sudden cardiac arrest is an intriguing question.

PMID- 21894249
TI  - The cardiovascular triad of dysfunctional angiogenesis.
AB  - Cerebral cavernous malformation is a clinically well-defined microvascular
      disorder predisposing to stroke; however, the major phenotype observed in
      zebrafish is the cardiac defect, specifically an enlarged heart. Less effort has
      been made to explore this phenotypic discrepancy between human and zebrafish.
      Given the fact that the gene products from Ccm1/Ccm2 are nearly identical between
      the two species, the common sense has dictated that the zebrafish animal model
      would provide a great opportunity to dissect the detailed molecular function of
      Ccm1/Ccm2 during angiogenesis. We recently reported on the cellular role of the
      Ccm1 gene in biochemical processes that permit proper angiogenic microvascular
      development in the zebrafish model. In the course of this experimentation, we
      encountered a vast amount of recent research on the relationship between
      dysfunctional angiogenesis and cardiovascular defects in zebrafish. Here we
      compile the findings of our research with the most recent contributions in this
      field and glean conclusions about the effect of defective angiogenesis on the
      developing cardiovascular system. Our conclusion also serves as a bridge for the
      phenotypic discrepancy between humans and animal models, which might provide some
      insights into future translational research on human stroke. 

PMID- 21894250
TI  - Disseminated molluscum contagiosum in a HIV-positive child. Improvement after
      therapy with 5% imiquimod.
AB  - BACKGROUND: Molluscum contagiosum (MC) is a frequent and usually benign cutaneous
      infection with molluscum contagiosum virus (MCV), affecting mainly children and
      young sexually active adults. With the emergence of HIV/AIDS, a new patient group
      at risk has been identified with often extensive skin involvement and
      recalcitrant disease. MAIN OBSERVATIONS: We report a case of a girl with connatal
      HIV-infection, suffering from extensive, disseminated MC. Due to multi
      resistance, an effective antiretroviral therapy could not be established for
      years, rendering an effective treatment of MC by established treatment options
      virtually impossible. An off-label use of imiquimod showed a marked improvement
      of lesion counts in this patient, whereas a complete clearance could only be
      achieved once effective antiretroviral therapy was introduced. CONCLUSIONS: We
      believe that imiquimod may represent a valuable treatment option for molluscum
      contagiosum especially in the context of marked immunosuppression, where
      sensitive areas like the face and neck are often involved and scarring must be
      avoided.

PMID- 21894252
TI  - Cicatricial upper and lower eyelid ectropion in an ichthyosis patient. Surgical
      correction.
AB  - BACKGROUND: Surgical correction of bilateral cicatricial upper and lower eyelid
      ectropion in an ichthyosis patient remains a challenge in clinical practice. MAIN
      OBSERVATIONS: A 24-year-old female patient presented to our clinic with bilateral
      upper and lower eyelid ectropion. Her skin over her entire body and face was dry
      and scaly. The diagnosis was cicatricial ectropion related in a patient with
      ichthyosis. The upper eyelids were treated by retroauricular full thickness skin
      grafts and upper eyelid lateral tarsal strip procedure. And lower eyelids were
      treated by cheek transposition grafts and lower eyelid lateral tarsal strip
      procedure. The upper and lower eyelids were corrected successfully with these
      surgical procedures. CONCLUSIONS: In patients with ichthyosis skin alterations in
      the eyelid cause shortening of the anterior lamella, subsequently resulting with
      ectropion. Successful surgical correction with skin grafts or transposition flaps
      can be performed to lenghten anterior lamella. Adding lateral tarsal strip
      procedure to skin grafting helps to maintain a beter lid margin apposition.

PMID- 21894251
TI  - Isolated Kaposi Sarcoma in two HIV negative patients.
AB  - BACKGROUND: Kaposi sarcoma (KS) is a neoplasm of the endothelial cells. It often
      manifests with multiple vascular nodules on the skin and other organs. It is a
      systemic, malignant and multifactorial disease and has a variable course. There
      are four types: classic, endemic, iatrogenic and HIV-associated. The primary
      presentation on the penis and face is uncommon and is mainly observed in HIV
      positive patients. Multiple treatment modalities are used including surgery,
      cryotherapy, electrosurgery, laser and radiation therapy. MAIN OBSERVATION: The
      authors present two cases of isolated Kaposi sarcoma in HIV negative, human
      herpes virus 8 (HHV-8) positive non immunocompromised patients. One case with
      facial KS and the other one with penile KS. Both were treated surgically with no
      recurrence in the following 6 months of the follow up period. CONCLUSIONS: Kaposi
      sarcoma is rare in HIV negative patients and is associated with HHV-8 infection.
      Lesions are usually solitary and can be treated surgically. It should be included
      in the differential diagnoses of penile and facial lesions that are clinically
      suspecious and resistent to therapy.

PMID- 21894253
TI  - A profound case of linear epidermal nevus in a patient with epidermal nevus
      syndrome.
AB  - BACKGROUND: Epidermal nevus syndrome is a multi-system disease with a wide
      spectrum of clinical presentation. Numerous specialists may be required to
      address its extra cutaneous manifestations. MAIN OBSERVATIONS: We report a severe
      case of epidermal nevus syndrome involving the oral cavity, pharynx, and central
      nervous system in addition to disfiguring skin lesions. CONCLUSIONS:
      Dermatologists are in a unique position to first render the diagnosis of
      epidermal nevus syndrome for young patients and ensure appropriate follow-up.

PMID- 21894254
TI  - Photoletter to the editor: Oral ulceration in pyoderma gangrenosum.
AB  - A 65-year-old woman presented with widespread necrotising cutaneous ulceration
      and oral involvement. Past history included rheumatoid arthritis, and a left
      nephrectomy.Examination revealed multiple violaceous undermined ulcers. Blood
      investigations showed an acute inflammatory response. Skin histopathology showed
      epidermal ulceration with acute and chronic inflammation. Direct
      immunofluorescence was negative. A diagnosis of pyoderma gangrenosum with oral
      involvement was made. Mycophenolate mofetil therapy resulted in complete
      resolution of her pyoderma gangrenosum. Her treatment was complicated by a left
      proteus mirabilis psoas abscess. This resolved following four weeks of
      antibiotics.Pyoderma gangrenosum with oral involvement is rare but has been
      linked with inflammatory bowel disease and hematological disorders. Oral pyoderma
      gangrenosum has not previously been described in rheumatoid arthritis. Primary
      psoas abscess is rare but can develop in immunocompromised patients. Proteus
      mirabilis has been reported in patients years after nephrectomy. This is a rare
      case of pyoderma gangrenosum with oral involvement.

PMID- 21894255
TI  - Photoletter to the editor: Trichomycosis (trichobacteriosis) axillaris.
AB  - Trichomycosis axillaris is a common tropical disease usually affecting the hair
      shafts of the axillae, characterized by nodular concretions along the hair shafts
      caused by Corynebacterium tenuis. We describe a 38-year-old patient with
      trichomycosis axillaris. Treatment, which included shaving of affected hair,
      followed by topical 3% erythromycin cream and clotrimazole powder was fully
      effective.

PMID- 21894257
TI  - Applying a New Model for Sharing Population Health Data to National Syndromic
      Influenza Surveillance: DiSTRIBuTE Project Proof of Concept, 2006 to 2009.
AB  - The Distributed Surveillance Taskforce for Real-time Influenza Burden Tracking
      and Evaluation (DiSTRIBuTE) project began as a pilot effort initiated by the
      International Society for Disease Surveillance (ISDS) in autumn 2006 to create a
      collaborative electronic emergency department (ED) syndromic influenza-like
      illness (ILI) surveillance network based on existing state and local systems and
      expertise. DiSTRIBuTE brought together health departments that were interested
      in: 1) sharing aggregate level data; 2) maintaining jurisdictional control; 3)
      minimizing barriers to participation; and 4) leveraging the flexibility of local
      systems to create a dynamic and collaborative surveillance network. This approach
      was in contrast to the prevailing paradigm for surveillance where record level
      information was collected, stored and analyzed centrally. The DiSTRIBuTE project
      was created with a distributed design, where individual level data remained local
      and only summarized, stratified counts were reported centrally, thus minimizing
      privacy risks. The project was responsive to federal mandates to improve
      integration of federal, state, and local biosurveillance capabilities. During the
      proof of concept phase, 2006 to 2009, ten jurisdictions from across North America
      sent ISDS on a daily to weekly basis year-round, aggregated data by day,
      stratified by local ILI syndrome, age-group and region. During this period, data
      from participating U.S. state or local health departments captured over 13% of
      all ED visits nationwide. The initiative focused on state and local health
      department trust, expertise, and control. Morbidity trends observed in DiSTRIBuTE
      were highly correlated with other influenza surveillance measures. With the
      emergence of novel A/H1N1 influenza in the spring of 2009, the project was used
      to support information sharing and ad hoc querying at the state and local level.
      In the fall of 2009, through a broadly collaborative effort, the project was
      expanded to enhance electronic ED surveillance nationwide.

PMID- 21894256
TI  - Altered expression of tissue remodeling genes in a mouse model of acute allergic
      rhinitis.
AB  - BACKGROUND: Osteogenesis, fibrosis, and scarring are prominent pathologic changes
      resulting from chronic sinonasal inflammation, and these tissue changes may
      increase the degree of disease symptomatology and the level of surgical
      difficulty. Members of the bone morphogenetic protein (BMP) and fibroblast growth
      factor (FGF) families of cytokines and the matrix metalloproteinase (MMP) family
      of endopeptidases are known to regulate tissue remodeling in other disease
      processes, but their role in acute and chronic sinonasal inflammation remains
      undefined. METHODS: A previously described mouse model of acute allergic rhinitis
      secondary to Aspergillus fumigatis exposure in BALB/C mice was used. Intranasal
      challenge was performed 1 week following intraperitoneal sensitization with A.
      fumigatis extract and mice were sacrificed 6 hours (n = 8) and 24 hours (n = 8)
      later. Additional mice were intranasally challenged 3 times per week and
      sacrificed at the end of 7 days (n = 8) and 21 days (n = 8). The snouts were
      processed for quantitative reverse-transcription polymerase chain reaction (RT
      PCR) and compared to untreated controls for messenger ribonucleic acid (mRNA)
      expression of BMP1, 2, 3, 4, 5, 6, 7, 8a, 8b, 9, 10, FGF1, 2, 3, 4, 5, 6, 7, 8,
      10, and MMP1a, 2, 3, 7, 8, 9, 12, and 14. Additional 21-day-old mice were
      prepared for sinonasal histopathology. Control mice were treated with the same
      protocol, with intraperitoneal phosphate-buffered saline (PBS) and intranasal PBS
      substituted for A. fumigatis extract. Untreated mice were used for additional
      comparison. RESULTS: Compared to both the PBS-treated and untreated control
      groups, statistically significant (p < 0.05) upregulation of MMP8 was observed in
      the 6-hour time point. Significant downregulation of MMP8 was observed at 1 week.
      Significant upregulation of FGF3 was observed at 1 week (p < 0.05). BMP3 and BMP5
      were significantly downregulated in the 1-week group (p < 0.05). The mice
      exhibited histologic sinonasal changes consistent with allergic inflammation.
      CONCLUSION: Intranasal exposure to A. fumigatis results in altered expression of
      several tissue remodeling cytokines at varying time points in the acute allergic
      rhinitis mouse model. These changes in cytokine regulation may subsequently
      contribute to sinonasal osteogenesis, scarring, and fibrosis as seen in chronic
      rhinosinusitis.

PMID- 21894258
TI  - Structure-based drug design of a new chemical class of small molecules active
      against influenza A nucleoprotein in vitro and in vivo.
AB  - We report preliminary results and a summary of a bottom-up approach to identify
      new, active, nontoxic, small-molecule antivirals designed to have a novel
      mechanism of action. We employed the procedure to identify 3-mercapto-1,2,4
      triazoles derivatives as potential NP inhibitors in silico and subsequently
      demonstrated the in vitro efficacy of the molecules against various strains of
      the influenza A virus. The most efficacious compounds were successfully tested in
      an in vivo influenza challenge experiment.

PMID- 21894259
TI  - Development of a Multi-modal Tissue Diagnostic System Combining High Frequency
      Ultrasound and Photoacoustic Imaging with Lifetime Fluorescence Spectroscopy.
AB  - We report the development and validate a multi-modal tissue diagnostic
      technology, which combines three complementary techniques into one system
      including ultrasound backscatter microscopy (UBM), photoacoustic imaging (PAI),
      and time-resolved laser-induced fluorescence spectroscopy (TR-LIFS). UBM enables
      the reconstruction of the tissue microanatomy. PAI maps the optical absorption
      heterogeneity of the tissue associated with structure information and has the
      potential to provide functional imaging of the tissue. Examination of the UBM and
      PAI images allows for localization of regions of interest for TR-LIFS evaluation
      of the tissue composition. The hybrid probe consists of a single element ring
      transducer with concentric fiber optics for multi-modal data acquisition.
      Validation and characterization of the multi-modal system and ultrasonic,
      photoacoustic, and spectroscopic data coregistration were conducted in a physical
      phantom with properties of ultrasound scattering, optical absorption, and
      fluorescence. The UBM system with the 41 MHz ring transducer can reach the axial
      and lateral resolution of 30 and 65 MUm, respectively. The PAI system with 532 nm
      excitation light from a Nd:YAG laser shows great contrast for the distribution of
      optical absorbers. The TR-LIFS system records the fluorescence decay with the
      time resolution of ~300 ps and a high sensitivity of nM concentration range.
      Biological phantom constructed with different types of tissues (tendon and fat)
      was used to demonstrate the complementary information provided by the three
      modalities. Fluorescence spectra and lifetimes were compared to differentiate
      chemical composition of tissues at the regions of interest determined by the
      coregistered high resolution UBM and PAI image. Current results demonstrate that
      the fusion of these techniques enables sequentially detection of functional,
      morphological, and compositional features of biological tissue, suggesting
      potential applications in diagnosis of tumors and atherosclerotic plaques.

PMID- 21894261
TI  - From bark to weed: the history of artemisinin.
AB  - In the 1970's, in China, some brilliant and courageous scientists carried out a
      research programme, which lead to the discovery of artemisinin derivatives and
      new quinoleines that are used today, in combination, as first line treatment of
      malaria.

PMID- 21894260
TI  - The antimalarial ferroquine: from bench to clinic.
AB  - Ferroquine (FQ, SSR97193) is currently the most advanced organo-metallic drug
      candidate and about to complete phase II clinical trials as a treatment for
      uncomplicated malaria. This ferrocene-containing compound is active against both
      chloroquine-susceptible and chloroquine-resistant Plasmodium falciparum and P.
      vivax strains and/or isolates. This article focuses on the discovery of FQ, its
      antimalarial activity, the hypothesis of its mode of action, the current absence
      of resistance in vitro and recent clinical trials.

PMID- 21894262
TI  - Pneumocystis jirovecii pneumonia in developing countries.
AB  - Pneumocystis pneumonia (PcP) is a serious fungal infection among
      immunocompromised patients. In developed countries, the epidemiology and clinical
      spectrum of PcP have been clearly defined and well documented. However, in most
      developing countries, relatively little is known about the prevalence of
      pneumocystosis. Several articles covering African, Asian and American countries
      were reviewed in the present study. PcP was identified as a frequent
      opportunistic infection in AIDS patients from different geographic regions. A
      trend to an increasing rate of PcP was apparent in developing countries from 2002
      to 2010.

PMID- 21894263
TI  - A study on the determination of risk factors associated with babesiosis and
      prevalence of Babesia sp., by PCR amplification, in small ruminants from Southern
      Punjab (Pakistan).
AB  - Babesiosis is a parasitic infection due to the multiplication of tick borne
      parasite, Babesia sp., in erythrocytes of host, which includes a wide variety of
      vertebrates including small ruminants causing decreased livestock output and
      hence economic losses. The objective of the present study was to establish a PCR
      based method for the detection of Babesia sp. in small ruminant population in
      Southern Punjab and to determine the risk factors involve in the spread of
      babesiosis. A total of 107 blood samples were collected from 40 sheep and 67
      goats in seven districts of Southern Punjab from randomly selected herds. Data on
      the characteristics of the animals and the herd were collected through
      questionnaires. 36 blood samples (34% of total) produced the DNA fragment
      specific for 18S rRNA gene of Babesia sp., by PCR amplification, of which 20 were
      sheep and 16 were goats. Samples from all seven district contained Babesia
      positive samples and prevalence varied between 18 to 68%. It was observed that
      male animals (P = 0.009) and young animals under one year of age (P = 0.01) were
      more prone to the parasite. It was observed that herds consist of more than 15
      animals (P = 0.007), composed of mixed species of small ruminants (P = 0.022),
      associated with dogs (P = 0.003) and dogs having ticks on their bodies (P =
      0.011) were among the major risk factors for the spread of babesiosis in small
      ruminants.

PMID- 21894264
TI  - Redescription of the male of Ixodes festai Rondelli, 1926 (Ixodida: Ixodidae) on
      specimens from Sardinia (Italy).
AB  - Ixodes festai Rondelli, 1926 is a poorly known bird parasite tick. Its immature
      forms have not been described yet, while the adult forms only insufficiently,
      especially the male. In this note the presence of the male of Ixodes festai for
      the first time in Sardinia (Italy) is reported and a detailed redescription is
      provided. Morphometric data as well as photographs performed both with optical
      and electron microscope (ESEM FEI Quanta 200) are also shown.

PMID- 21894265
TI  - [Two new species of fleas (Siphonaptera: Ctenophthalmidae & Rhopalopsyllidae)
      from Chile].
AB  - Agastopsylla guzmani n. sp. (Ctenophthalmidae) and Delostichus degus n. sp.
      (Rhopalopsyllidae) are described. A key is proposed for the genus Agastopsylla;
      for the genus Delostichus, a brief comparison is made with D. incisus and D.
      ojedai described after the issue of the Catalogue of Smit (1987).

PMID- 21894266
TI  - [Gryphopsylla segregata Beaucournu & Sountsov, 1999: new status for G. jacobsoni
      segregata, description of the female and proposition of a new key for the genus
      Gryphopsylla (Siphonaptera - Pygiopsyllidae - Stivaliinae)].
AB  - The recent collection of a female of Gryphopsylla jacobsoni segregata Beaucournu
      & Sountsov, 1999 from northern Borneo allowed us to better clarify the taxonomic
      status of this flea and confirm that G. jacobsoni and G. segregata are distinct
      species. We describe the female of G. segregata and revised the identification
      key of the genus.

PMID- 21894267
TI  - Prevalence of ectoparasitic arthropods on wild animals and cattle in the Las
      Merindades area (Burgos, Spain).
AB  - This paper reports the prevalence of ectoparasitic arthropods in sampled groups
      of wild (n = 128; 16 species) and domestic (n = 69; 3 species) animals in the Las
      Merindades area of the Province of Burgos, Spain. The study revealed that wild
      animals were more infested and with a wider variety of ectoparasites than
      domestic animals. The parasitic prevalence was 67% for wild animals and 48% for
      livestock. In this way, 39% of animals were infected by ticks. Ixodes ricinus and
      Ixodes hexagonus were the most prevalent species whereas Dermacentor reticulatus
      showed affinity for the fox and wolf. The overall prevalence of parasitisation by
      fleas was 27%. Ctenophthalmus spp. showed the wider range host in wild animals,
      while Pulex irritans was the most frequent specie found. The parasitic
      prevalences by lice (Trichodectes melis, Trichodectes canis and Trichodectes
      mustelae) and by mite (Neotrombicula spp., Laelaps agilis and Sarcoptes scabiei)
      were 4% and 12%, respectively. In both cases only wild animals were found
      parasited.

PMID- 21894268
TI  - The steppe species of gastrointestinal nematodes of small ruminants, with a focus
      on Marshallagia: climate as a key determinant.
AB  - We intended to relate the geographic distribution of ruminant gastrointestinal
      nematodes in relation to steppe climate (and vegetation). Data are either from
      literature or from newly acquired/available results. Simple or more sophisticated
      meteorological indices were used to characterize the climate. Regression analyses
      were used to correlate climatic factors and presence of endoparasites from steppe
      areas. The distribution of one (Marshallagia) out of five endoparasite genera was
      concentrated mostly in steppic areas whereas other species were found also in
      other areas. In wild hosts the distribution of Marshallagia was much larger from
      Sptizberg to New World (northern territories in Canada or extreme south of
      America). In domestic small ruminants the presence of Marshallagia was identified
      more frequently and constantly in the area of original domestication and its
      early diffusion (from Northern Africa to Kashmir, Caucasia). The distribution of
      this parasite was correlated to low rainfalls which were not the case for all
      other endoparasites. After host switch (reindeer or south America camelids), it
      has expanded in other climatic areas, either colder or dryer.

PMID- 21894269
TI  - New data in France on the trematode Alaria alata (Goeze, 1792) obtained during
      Trichinella inspections.
AB  - The trematode Alaria alata is a cosmopolite parasite found in red foxes (Vulpes
      vulpes), the main definitive host in Europe. In contrast only few data are
      reported in wild boars (Sus scrofa), a paratenic host. The aim of this paper is
      to describe the importance and distribution of Alaria alata mesocercariae in wild
      boars, information is given by findings of these larvae during Trichinella
      mandatory meat inspection on wild boars' carcasses aimed for human consumption.
      More than a hundred cases of mesocercariae positive animals are found every year
      in the East of France. First investigations on the parasite's resistance to deep
      freezing in meat are presented in this work.

PMID- 21894270
TI  - Natural vertical transmission of dengue viruses by Aedes aegypti in Bolivia.
AB  - The natural transmission of dengue virus from an infected female mosquito to its
      progeny, namely the vertical transmission, was researched in wild caught Aedes
      aegypti during an important outbreak in the town of Santa Cruz de la Sierra,
      Bolivia. Mosquitoes were collected at the preimaginal stages (eggs, larvae and
      pupae) then reared up to adult stage for viral detection using molecular methods.
      Dengue virus serotypes 1 and 3 were found to be co-circulating with significant
      higher prevalence in male than in female mosquitoes. Of the 97 pools of Ae.
      aegypti (n = 635 male and 748 female specimens) screened, 14 pools, collected in
      February-May in 2007, were found positive for dengue virus infection: five DEN-1
      and nine DEN-3. The average true infection rate (TIR) and minimum infection rate
      (MIR) were respectively 1.08% and 1.01%. These observations suggest that vertical
      transmission of dengue virus may be detected in vectors at the peak of an
      outbreak as well as several months before an epidemic occurs in human population.

PMID- 21894271
TI  - Autism spectrum disorders.
AB  - In this article we use BEACH data to examine changes in the management rate of
      autism spectrum disorders (ASDs) from 2001 to 2011 in children aged <18 years. We
      also look at encounters where autism was managed during 2006-2011.

PMID- 21894272
TI  - Is my child normal? Milestones and red flags for referral.
AB  - BACKGROUND: Developmental problems in young children are common and have lifelong
      implications for health and wellbeing. Early detection of developmental problems
      provides an opportunity for early intervention to shift a child's developmental
      trajectory and optimise their potential. OBJECTIVE: This article describes and
      recommends a broader concept of developmental surveillance that should replace
      the reliance on traditional methods of early detection such as milestone
      checklists, parent recall, developmental screening tests and clinical judgment.
      DISCUSSION: General practitioners and other professionals in regular contact with
      children and their families are ideally placed to monitor a child's development,
      detect problems early and to intervene to optimise the child's development and
      thus promote long term health and wellbeing. Developmental surveillance involves
      eliciting parental concerns, performing skilled observations of the child, and
      providing guidance on health and development issues that are relevant to the
      child's age and the parents' needs. Standardised tools are available to assist
      GPs to elicit parental concerns and guide clinical decision making.

PMID- 21894273
TI  - Autism spectrum disorders.
AB  - BACKGROUND: Autism spectrum disorders (ASDs) are serious neurodevelopmental
      disorders affecting approximately one in 160 Australians. Symptoms are apparent
      during the second year of life causing impairments in social interaction,
      communication and behaviour with restricted and stereotyped interests. OBJECTIVE:
      To increase the general practitioner's awareness of the presenting symptoms of
      ASDs and their associated problems in children, screening for ASDs, and the
      assessment process, treatment options and outcomes. DISCUSSION: This article
      discusses the five red flags that are autism alerts in young children. These red
      flags can enable GPs to play a key surveillance role in determining which young
      children might require further screening and referral for an ASD assessment.
      Because ASDs are lifelong, neurodevelopmental disorders and symptoms change over
      time. Therefore the GP has an ongoing role to support, educate and advise
      parents, other carers and the individual with an ASD. Treatment and
      pharmacological interventions are also discussed.

PMID- 21894274
TI  - Problem behaviour in children--an approach for general practice.
AB  - BACKGROUND: Around 12% of Australian children aged 4-12 years experience
      externalising behavioural problems such as aggression and hyperactivity.
      Similarly, around 12% experience internalising problems such as anxiety and
      depression. Other common behaviour problems, such as temper tantrums, arise as
      the child strives to achieve developmental milestones. OBJECTIVE: This article
      reviews externalising behavioural problems and common developmental behavioural
      problems in children from toddler to school age. Diagnosis, management and when
      to refer are discussed. DISCUSSION: Behavioural difficulties arise as a result of
      an interaction between biological vulnerabilities and environmental stressors. In
      most cases, behavioural difficulties are temporary, and occur as children strive
      to achieve developmental milestones. General management includes reinforcing
      positive behaviour, using a consistent approach and setting limits and clear
      consequences for misbehaviour. Children should be referred when there are
      concerns about their safety or development.

PMID- 21894275
TI  - Breastfeeding--evidence based guidelines for the use of medicines.
AB  - BACKGROUND: General practitioners may consider prescribing medicines for
      breastfeeding women during the postpartum period. Most medicines can be used
      safely during breastfeeding at the recommended dose, however there are exceptions
      that necessitate caution. OBJECTIVE: This article provides an evidence based
      review of medicines used for common situations and their compatibility with
      breastfeeding. DISCUSSION: Breastfeeding women typically use relatively few
      medicines, and generally these are compatible with breastfeeding. If other
      medicines are required, information on their safety during breastfeeding can be
      accessed from pharmacy departments at maternity hospitals or from online
      resources.

PMID- 21894277
TI  - Patient information--nerve conduction studies.

PMID- 21894276
TI  - Nerve conduction studies.
AB  - This article forms part of our 'Tests and results' series for 2011 which aims to
      provide information about common tests that general practitioners order
      regularly. It considers areas such as indications, what to tell the patient, what
      the test can and cannot tell you, and interpretation of results.

PMID- 21894278
TI  - Hyperpigmentation--a case study.

PMID- 21894280
TI  - Decision support systems--a general practice research journey.

PMID- 21894279
TI  - Proton pump inhibitors--uncommon adverse effects.
AB  - BACKGROUND: Proton pump inhibitors (PPIs) are one of the most popularly
      prescribed drugs in Australia for conditions such as gastro-oesophageal reflux
      disease, peptic ulcer disease and functional dyspepsia. Despite their good safety
      profile, PPIs have potential adverse effects, yet they are often overprescribed
      and without a clear indication. OBJECTIVE: This article reviews the uncommon
      adverse effects of PPIs and provides recommendations for managing patients
      receiving this therapy. DISCUSSION: Uncommon adverse effects include rebound acid
      hypersecretion syndrome, fragility fractures, interstitial nephritis, electrolyte
      derangements, pneumonia, enteric infection and vitamin B12 deficiency. General
      practitioners should be aware of these potential adverse effects and ensure that
      PPIs are used appropriately and where benefit clearly outweighs any harmful
      effects.

PMID- 21894281
TI  - Fibromyalgia--should we be testing and treating for vitamin D deficiency?
AB  - AIM: This review aims to synthesise the evidence regarding any association
      between vitamin D deficiency and fibromyalgia, addressing whether general
      practitioners should be testing and treating these patients for vitamin D
      deficiency. METHODS: A systematic literature review was performed, using MEDLINE
      as the primary database, to find and critically appraise all relevant research
      fulfilling inclusion criteria from January 1990 until September 2010. RESULTS:
      There were conflicting results in the cross sectional studies obtained, with no
      association in studies using control groups and mixed results in larger
      population based studies. One adequately powered randomised controlled trial
      suggests fibromyalgia pain is not improved by vitamin D supplementation.
      DISCUSSION: The evidence for an association between fibromyalgia and vitamin D
      deficiency is inconclusive, with no improvement in pain on supplementation.
      However, patients with concurrent risk factors for deficiency should be tested
      and treated for vitamin D deficiency to minimise osteoporosis risk and maximise
      muscular strength.

PMID- 21894282
TI  - Traditional Chinese medicine--women's experiences in the treatment of
      infertility.
AB  - BACKGROUND: Infertility affects about 15% of couples. Many women proceed to
      reproductive clinics for in vitro fertilisation, with some exploring a range of
      alternative or complementary options. We explored women's experiences with
      traditional Chinese medicine (TCM) for the treatment of infertility. METHODS: We
      interviewed 25 women with primary or secondary infertility, recurrent miscarriage
      or stillbirth who had consulted TCM practitioners. We explored women's experience
      of TCM and fertility clinics and analysed interviews thematically. RESULTS: Women
      appreciated the noninvasive diagnostic techniques TCM practitioners used to
      identify 'imbalances' causing infertility, learnt how to assess fertility
      indicators, and valued the focused personal care provided. All noticed improved
      menstrual cycles. Women wished for integration of holistic therapies in
      infertility management. DISCUSSION: Our study highlights the need for patient
      centred care and fertility education, and suggests that some women see a possible
      role for TCM as part of infertility management.

PMID- 21894283
TI  - Medical journal covers--an analysis of gendered images and how these might
      influence best practice.
AB  - BACKGROUND: Images convey a concept or message to their audience. In medical
      communications, social expectations and stereotypes can be transferred through
      language, images and practices just as they can in the lay press. Most medical
      journals utilise images on their front covers, with the aim of enticing readers
      to open the journal. OBJECTIVE: This article explores the use of image on the
      covers of two medical journals. It investigates the concepts of gender and the
      patient-doctor relationship used in these images through a content analysis.
      DISCUSSION: While the images investigated are engaging and sometimes amusing, we
      explore meanings beyond our engagement as a viewer. The discussion focuses on the
      need for promotion of best practice, in words and pictures, to model best
      professional practice.

PMID- 21894284
TI  - Workers' compensation forms--a guide for GPs.
AB  - Workers' compensation provides financial benefits for injured workers. The
      general practitioner has a pivotal role in the completion of necessary documents
      such as medical certificates, medical reports and treating practitioner
      questionnaires. Before completing such documents, the GP must complete a thorough
      medical assessment. This article describes the important elements of this
      assessment, the information required in workers' compensation documents, and the
      responsibilities of the GP and worker (patient) in completing these documents.

PMID- 21894285
TI  - A competency history--an additional model of history taking.
AB  - BACKGROUND: Taking a medical history is an effective way of finding out important
      information about the patient and their presenting problem/s but this approach
      may inadvertently be disempowering for the patient. An increased sense of agency
      can increase the likelihood of behavioural change, so facilitating empowerment of
      the patient in the context of a medical consultation is an important challenge
      for general practitioners. OBJECTIVE: This article describes an alternative or
      additional model of history taking - the 'competency history'. It describes its
      theoretical base, components and appropriate use, and gives examples of how a
      competency history can be used in general practice. DISCUSSION: A competency
      history uses strength based empowerment approaches and is especially appropriate
      with patients who have a poor sense of agency. The core elements of a competency
      history include an understanding of the patient's past and current context,
      respect for the patient's expertise and strength based interventions, including
      alternative narratives and solution focused conversations. Another important
      aspect of this approach is to allow the patient to take the initiative in making
      a change in their behaviour, and to take responsibility for their health. Taking
      a competency history is a useful additional skill for GPs, and may be a valuable
      addition to undergraduate medical training.

PMID- 21894286
TI  - Liver cirrhosis noninvasive assessment with Acoustic Radiation Force Impulse
      Imaging.

PMID- 21894287
TI  - Liver biopsy in the era of elastography.

PMID- 21894288
TI  - Ultrasound guided core needle biopsy of soft tissue tumors; a fool proof
      technique?
AB  - AIM: To assess technical and lesion related factors affecting the quality of
      ultrasound guided core needle biopsy (CNB) of musculoskeletal soft tissue tumors.
      MATERIALS AND METHODS: Data of 223 CNBs were evaluated in a retrospective study.
      Diagnostic yield was calculated for all lesions on the basis of lesion location
      (extremity/torso), examiner, biopsy needle gauge/length and number of acquired
      samples. Diagnostic accuracy was calculated for surgical lesions (n= 113) based
      on final specimen histology. Chi-square test based Phi-coefficient calculations
      were performed to search for associations between each factor and diagnostic
      yield. RESULTS: Overall diagnostic yield was 94.6%. There was no significant
      difference in diagnostic yield between specialist biopsies (96.8%) and resident
      biopsies (93.1%), between lesions located in the extremities (94.9%) and lesions
      in the torso (93.8%) and on the basis of needle gauge or number of acquired
      cores. Diagnostic accuracy was 100% for surgical lesions. The only factor
      influencing the quality of CNB was lesion composition (repeat biopsies in myxoid
      and/or inhomogeneous lesions). CONCLUSION: The most important aspects to achieve
      constant high quality results with ultrasound guided CNBs in the work-up of
      musculoskeletal soft tissue tumors are expertise concerning identification and
      targeting of viable tumor components and strict adherence to a quality controlled
      biopsy procedure. Once this is achieved, technical factors have almost no effect
      on the quality of CNB.

PMID- 21894289
TI  - The influence of liver residual mass on the values of Acoustic Radiation Force
      Impulse Elastography (ARFI) in cirrhotic patients.
AB  - AIM: The aim of our study was to assess the influence of liver residual mass in
      cirrhotic patients on the liver stiffness (LS), measured by ARFI elastography.
      METHODS: Two hundreds eleven cirrhotic patients were enrolled. To evaluate the
      liver residual mass, the Child-Pugh and MELD scores were used and 10 valid ARFI
      measurements were performed. The correlation between Child-Pugh, MELD scores and
      the LS were evaluated. RESULTS: Valid ARFI measurements were not obtained in 3
      patients. A direct, very low correlation between the LS values and the Child-Pugh
      (r=0.264, p<0.001) and MELD scores (r=0.194, p=0.005) was found. A direct, low
      correlation between LS measurements and total bilirubin (r=0.271, p<0.001) and an
      inverse, low correlation with albumin (r=-0.270, p<0.001), prothrombin time (r=
      0.196, p=0.006), cholinesterase (r=-0.241, p=0.003) was obtained. The LS mean
      values were statistically significant higher in patients with Child-Pugh class B
      vs. A (p=0.002) and in Child-Pugh C vs. A (p<0.001). The values were not
      significantly different in patients with Child-Pugh B vs. C (p=0.06).
      CONCLUSIONS: Higher values of LS measurements by means of ARFI could be an
      indicator of decreased liver functional reserve, evaluated by means of Child Pugh
      or Meld scores.

PMID- 21894290
TI  - Effect of severity of steatosis as assessed ultrasonographically on hepatic
      vascular indices in non-alcoholic fatty liver disease.
AB  - Early monitoring of non-alcoholic fatty liver disease (NAFLD) progression in
      obese patients is important to avoid the development of complications associated
      with fatty infiltration. THE AIM: of this study was to investigate the
      relationship between the degrees of fatty infiltration and reduced vascular
      compliance in NAFLD patients in the three main hepatic vessels. MATERIAL AND
      METHODS: Two hundred and fourty subjects were enrolled in the study. They were
      divided into 4 groups: 60 controls, 60 grade 1 NAFLD patients, 60 grade 2 NAFLD
      patients and 60 grade 3 NAFLD patients. After US confirmation of the presence and
      grade of NAFLD, the peak and mean portal vein velocity (PPVV and MPVV,
      respectively), the hepatic artery resistance index (HARI), and the phasicity of
      the hepatic vein were measured. RESULTS: The PPVV was 19.6 +/- 2.4 cm/sec in
      patients with grade 1 fatty liver, 17.6 +/- 1.2 cm/sec in grade 2 and 15.4 +/-
      1.1 cm/sec in grade 3. The MPVV was 16.6 +/- 2.4 cm/sec in patients with grade 1
      fatty liver, 16.6 +/- 2.9 cm/sec in grade 2 and 12.7 +/- 0.7 cm/sec in grade 3.
      The HARI was 0.75 in patients with grade 1 fatty liver, 0.68 in grade 2 and 0.64
      in grade 3. There was an inverse relationship between PPVV, MPVV and HARI and
      different grades of fatty liver in patients (p = 0.001 for PPVV (Figure 7) and
      HARI, p = 0.006 for MPVV. CONCLUSION: The values of the investigated liver blood
      flow parameters were inversely correlated with the fatty infiltration grading.
      Fatty infiltration can severely influence hepatic blood flow, pointing attention
      to the importance of early diagnosis and the need for hepatic vessel flow
      abnormalities characterization in the NAFLD population.

PMID- 21894291
TI  - The role of color histograms in predicting the prognosis of patients with
      digestive tract adenocarcinoma.
AB  - OBJECTIVES: To establish the correlation between the degree of vascularisation
      detected using power Doppler ultrasonography in digestive tract adenocarcinoma
      and the prognosis of these patients. MATERIAL AND METHOD: Ultrasonography was
      performed in 45 patients diagnosed with digestive tract adenocarcinoma (16
      stomach-35.6%, 6 cecum and ascending colon-13.3%, 2 transverse colon-4.4%, 5
      descending colon 11.1%, 13 sigmoid colon-28.9%, and 3 rectum-6.7%). The degree of
      maximum tumor vascularization was determined using the highest percentage of
      colored pixels obtained in the histogram- maximum color pixels density (MCPD).
      The hepatic Doppler perfusion index (HDPI) was also calculated. The presence and
      development of liver metastases was evaluated by ultrasonography and computed
      tomography. The patients were monitored for a period of 18 months. The results of
      each method in detecting and predicting the development of liver metastases were
      compared. RESULTS: MCPD and HDPI had fairly similar results (p>0.05) in
      establishing the positive and negative predicting values for the entire group of
      patients with liver metastasis (55.9% compared to 66.7%, p>0.05, and 53.3%,
      compared to 54.6%, p>0.05) and the group that developed liver metastases during
      follow-up (80.0% compared to 90.0%, p>0.05, and 61.5%, compared to 75.0%,
      p>0.05). When comparing MCPD and HDPI for the group of patients who had or
      developed metastases, MCPD had an equal sensitivity (86.4%, compared to 90.9%, p
      >0.05), a higher specificity (65.0% compared to 46.5%, p<0.05), but a lower
      accuracy (60.0% compared to 73.3%, p<0.05). In detecting patients who developed
      metastases during the 18 months follow-up, MCPD had a superior sensitivity (85.7%
      compared to 64.3%, p<0.05), a lower specificity (66.7% compared to 88.9%, p<0.05)
      and an equal accuracy (78.3% vs. 73.9%, p >0.05.). CONCLUSIONS: The calculation
      of MCPD using color histograms can be a simple and quick method in the evaluation
      and prognosis of patients with digestive tract adenocarcinoma.

PMID- 21894292
TI  - Association between fatty liver disease and carotid atherosclerosis in patients
      with uncomplicated type 2 diabetes mellitus.
AB  - BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a clinic-pathological
      syndrome closely associated with obesity, dyslipidemia, diabetes and
      atherosclerosis. Some authors suggest that NAFLD is, in fact, another component
      of the metabolic syndrome. AIM: To determine the prevalence of NAFLD in diabetes
      mellitus (DM) patients, and to evaluate the carotid artery status in these
      patients. METHODS: Fifty six patients with uncomplicated type 2 DM were enrolled.
      Hepatic steatosis (HS) and carotid atherosclerosis (intima-media thickness - IMT)
      were evaluated by ultrasonography. Plasma liver function tests and other
      biochemical blood measurements were determined. RESULTS: HS was found in 38
      patients (67.8%) with DM. Subjects with HS had higher values for body mass index,
      diastolic blood pressure, mean blood pressure and triglycerides, and lower HDL
      cholesterol concentration, but there were no differences regarding IMT between DM
      patients with or without HS. Behavioral variables (smoking, diet, and
      sedentarism), fasting plasma glucose, and LDL cholesterol levels, also, did not
      significantly differ between subjects with and without HS. CONCLUSION: DM
      patients with HS in our study showed a cluster of cardiovascular risk factors but
      non-significant carotid atherosclerosis. The detection of HS by abdominal
      ultrasound should alert to the existence of a higher cardiovascular risk, but in
      DM this is still under discussion, the results being still unconfirmed.

PMID- 21894293
TI  - Contrast-enhanced ultrasonography in inflammatory arthritis.
AB  - The degree of inflammation is the keystone of therapy management in rheumatoid
      arthritis and other arthritides. The assessment of synovial perfusion using power
      Doppler ultrasound is an important point in the quantification of the joint
      inflammation but it is limited by the subjectivity of the vascularization grading
      and incapacity to detect flows in very small vessels. Contrast agent improves the
      ultrasound ability to depict and quantify blood flows in synovitis. Contrast
      enhanced ultrasonography (CEUS) better differentiates synovitis from collection
      and distinguishes the active synovitis from inactive fibrotic or necrotic pannus.
      Quantitative assessment of inflammation is possible analyzing the time-intesity
      curves and by the correct measurement of the synovial thickness. The additional
      informations and the diagnostic value of CEUS in arthritides are still
      controversial but its excellent imaging of synovial vessels open the way for
      further clinical applications. This review aims to discuss the actual knowledges
      of CEUS in inflammatory arthritis.

PMID- 21894294
TI  - Thoracic wall ultrasonography - normal and pathological findings. Pictorial
      essay.
AB  - Ultrasonography represents an efficient diagnosis method for thoracic pathology
      evaluation. The diseases of the pleura and thoracic wall receive the greatest
      benefit from the ultrasound examination. Establishing the cause of an acute
      thoracic pain or assessing a palpable tumor may easily benefit from essential
      data provided by ultrasonography. Afterwards it is possible to use a
      complementary imaging method or to perform US guided interventional procedures.
      This pictorial presents the ultrasonographic aspects of thoracic wall pathology,
      considering also differential diagnosis issues.

PMID- 21894295
TI  - Ultrasonographic diagnosis of congenital hydrometrocolpos in prenatal and newborn
      period: a case report.
AB  - Our purpose is to present the ultrasonographic findings of a rare case of
      prenatally and postnatally congenital hydrometrocolpos secondary to imperforate
      hymen. By ultrasonography (US) at 38 weeks of gestation, a retrovesical, 60 x 43
      mm pelvic cystic mass, was demonstrated in a female fetus. After delivery, US of
      the newborn revealed a 77 x 60 mm retrovesical, pear-shaped cystic structure with
      internal echoes, interpreted as congenital hydrometrocolpos. Mild
      pelvicaliectasis in the left kidney was associated. At physical examination
      imperforate hymen was detected and a hymenotomy was done. After the hymenotomy,
      complete regression of the hydrometrocolpos and of the left renal
      pelvicaliectasis was demonstrated sonographically.

PMID- 21894296
TI  - Superficial leiomyosarcoma of the scalp: a case report.
AB  - We present the case of a 91-year old female, with no family history of
      malignancy, diagnosed with primary superficial leiomyosarcoma G1 of the scalp
      with frontal bone lysis and intracranial extension. The particularity of this
      case is the rarity of this tumor and the uncommon location. Also the bone
      involvement, present in our case, has been seen only in a reduced number of
      patients, approximately 10% of the cases.

PMID- 21894297
TI  - Ectopic intrathyroid parathyroid adenoma: diagnostic and therapeutic challenges
      due to multiple osteolytic lesions. Case report.
AB  - Intrathyroid parathyroid adenoma is a rare lesion. Its location is usually
      achieved by cervical ultrasound and scintigraphy. We present the case of a 48
      years old woman admitted for malaise, weight loss, generalized bone pain, and
      important limitation of hip and scapular-humeral joints mobility. Cervical
      ultrasound identified a 4 cm nodular mass in the right thyroid lobe. Computed
      tomography revealed multiple osteolytic lesions in the pelvis, femur, ribs,
      phalanx, and humerus. Imagery and elevated serum levels of calcium and
      parathormone led to primary hyperparathyroidism, right parathyroid adenoma and
      bone "brown tumors". Intraoperatively, the adenoma was found in intrathyroid
      location. Total right lobectomy was performed. Postoperatively, the patient
      developed "hungry bone" syndrome requiring prolonged calcium and vitamin D
      treatment.

PMID- 21894298
TI  - A rare case of primary tuberculous pyomyositis. Case report.
AB  - Tuberculosis involving the soft tissue as extending from adjacent bone or joint
      is well recognized. However, the primary tuberculous pyomyositis is rare. Due to
      atypical presentation the diagnosis is often delayed. We report one case of
      primary tuberculous pyomyositis of the thigh in an immunocompromised patient.
      Tuberculous myositis should be suspicioned, in immunocompromised patients with
      unexplained soft tissue swelling, especially in endemic area.

PMID- 21894299
TI  - Ultrasonography of the uterus and ovaries.
AB  - Ultrasonography is the most frequently used imaging investigation in the
      assessment of the female genital tract. Most often the uterus and ovaries are
      evaluated with the help 2D transabdominal or endovaginal ultrasonography. The
      interpretation of the ultrasonographic data in order to establish the diagnosis
      of the main uterine and ovarian pathologies requires information about the
      examination technique and proper knowledge of the female genital tract ultrasound
      anatomy.

PMID- 21894301
TI  - Contrast-enhanced ultrasound for the evaluation of focal liver lesions - a
      multicenter trial in Romania.

PMID- 21894302
TI  - Macrocyclic receptor for pertechnetate and perrhenate anions.
AB  - The design and synthesis of a neutral macrocyclic host that is capable of
      perrhenate and pertechnetate recognition is described. The anion affinities and
      underlying coordination modes were estimated by several experimental and
      theoretical methods including a new technique--reverse (99)Tc NMR titration.

PMID- 21894311
TI  - Inhibition of peroxynitrite- and peroxidase-mediated protein tyrosine nitration
      by imidazole-based thiourea and selenourea derivatives.
AB  - In the present study, the synthesis and characterization of a series of N
      methylimidazole-based thiourea and selenourea derivatives are described. The new
      compounds were also studied for their ability to inhibit peroxynitrite (PN)- and
      peroxidase-mediated nitration of protein tyrosine residues. It has been observed
      that the selenourea derivatives are more efficient than the thiourea-based
      compounds in the inhibition of protein nitration. The higher activity of
      selenoureas as compared to that of the corresponding thioureas can be ascribed to
      the zwitterionic nature of the selenourea moiety. Single crystal X-ray
      diffraction studies on some of the thiourea and selenourea derivatives reveal
      that the C=S bonds in thioureas possess more of double bond character than the
      C=Se bonds in the corresponding selenoureas. Therefore, the selenium compounds
      can react with PN or hydrogen peroxide much faster than their sulfur analogues.
      The reactions of thiourea and selenourea derivatives with PN or hydrogen peroxide
      produce the corresponding sulfinic or seleninic acid derivatives, which upon
      elimination of sulfurous/selenous acids produce the corresponding N
      methylimdazole derivatives.

PMID- 21894312
TI  - An aldol approach to the enantioselective synthesis of (-)-oseltamivir phosphate.
AB  - A formal asymmetric synthesis of the antiviral agent (-)-oseltamivir phosphate is
      achieved using two aldol reactions as key steps.

PMID- 21894320
TI  - Fluorescent silver nanoclusters in hybridized DNA duplexes for the turn-on
      detection of Hg2+ ions.
AB  - Using the Hg(2+)-mediated T-T formation to strengthen the DNA duplexes and
      influence the configuration of fluorescent Ag NCs-forming sequences, a turn-on
      fluorescence detection method for Hg(2+) has been established.

PMID- 21894321
TI  - 9-H-9-Borafluorene dimethyl sulfide adduct: a product of a unique ring
      contraction reaction and a useful hydroboration reagent.
AB  - The dimethyl sulfide adduct 2(DMS) is a crystalline storage form of the unstable
      hydroboration reagent 9-H-9-borafluorene (2); 2(DMS) is available by the addition
      of DMS to either in situ generated [2](2) or 1,2-(2,2'-biphenylylene)diborane(6)
      (7).

PMID- 21894322
TI  - Molecular property-affinity relationship of the interaction between dietary
      polyphenols and bovine milk proteins.
AB  - The relationship between the molecular properties of dietary polyphenols and
      their affinities for bovine milk proteins (BMP) was investigated. The affinities
      of polyphenols for BMP were determined by means of fluorescence titration. The
      affinities of polyphenols for BMP increased with increasing partition coefficient
      and decreased with increasing hydrogen bond acceptor number of the polyphenol.
      From this point, the hydrophobic force played an important role in the binding
      interaction between polyphenols. It was found that the topological polar surface
      area value decreases with increasing binding constant of the polyphenol for BMP,
      which illustrates that the glycosylation of hydroxyl groups in polyphenols
      weakens their binding affinity for BMP. A strong correlation between Mulliken
      electronegativity and binding affinity was found (R = 0.64626), and Mulliken
      electronegativity values were found to increase with increasing binding constant
      of polyphenols for BMP. This illustrates that electrostatic interactions play a
      key role in binding dietary polyphenols to BMP.

PMID- 21894323
TI  - Structure of modified epsilon-polylysine micelles and their application in
      improving cellular antioxidant activity of curcuminoids.
AB  - The micelle structure of octenyl succinic anhydride modified epsilon-polylysine
      (M-EPL), an anti-microbial surfactant prepared from natural peptide epsilon
      polylysine in aqueous solution has been studied using synchrotron small-angle X
      ray scattering (SAXS). Our results revealed that M-EPLs formed spherical micelles
      with individual size of 24-26 A in aqueous solution which could further aggregate
      to form a larger dimension with averaged radius of 268-308 A. Furthermore, M-EPL
      micelle was able to encapsulate curcuminoids, a group of poorly-soluble bioactive
      compounds from turmeric with poor oral bioavailability, and improve their water
      solubility. Three loading methods, including solvent evaporation, dialysis, and
      high-speed homogenization were compared. The results indicated that the dialysis
      method generated the highest loading capacity and curcuminoids water solubility.
      The micelle encapsulation was confirmed as there were no free curcuminoid
      crystals detected in the differential scanning calorimetry analysis. It was also
      demonstrated that M-EPL encapsulation stabilized curcuminoids against hydrolysis
      at pH 7.4 and the encapsulated curcuminoids showed elevated cellular antioxidant
      activity compared with free curcuminoids. This work suggested that M-EPL could be
      used as new biopolymer micelles for delivering poorly soluble
      drugs/phytochemicals and improving their bioactivities.

PMID- 21894324
TI  - Is iron status associated with highly unsaturated fatty acid status among
      Canadian Arctic Inuit?
AB  - Impaired fatty acid synthesis was noted in iron deficient animal models. Human
      data, however, are scarce. Although Canadian Inuit have a traditional diet rich
      in heme iron and long chain n-3 fatty acids, recent literature has also indicated
      the presence of prevalent iron deficiency. We aimed to explore whether the
      presence of iron deficiency would affect fatty acid status and an estimate of the
      activity of desaturase 5 (Delta5), which is crucial in the biosynthesis of highly
      unsaturated n-3 fatty acids among Canadian Inuit. Erythrocyte membrane fatty acid
      composition was utilized as an indicator of fatty acid status and serum ferritin
      and circulating hemoglobin level were measured as the indicators of iron status.
      Data analyzed were collected among 1511 Canadian Inuit adult participants in the
      International Polar Year Inuit Health Survey, 2007-2008. Only 13.7% of survey
      participants had iron deficiency; however, serum ferritin showed a moderate
      positive association with highly unsaturated n-3 fatty acids after adjusting for
      age, waist and C-reactive protein (r = 0.172, P < .0001). Serum ferritin
      correlated significantly with Delta5 after further adjusting for highly
      unsaturated n-3 fatty acids (r = 0.126, P < .0001). Although the current study
      only demonstrated a weak link between ferritin and Delta5, the latter association
      underscores a possible health risk caused by a nutrient interaction related to
      reduced iron intake and decreased highly unsaturated n-3 fatty acid biosynthesis.
      Future studies are recommended to evaluate iron status in relation to highly
      unsaturated n-3 fatty acid biosynthesis and status among indigenous people
      undergoing rapid dietary transitions.

PMID- 21894325
TI  - Protective effects of prescription n-3 fatty acids against impairment of spatial
      cognitive learning ability in amyloid beta-infused rats.
AB  - Deposition of amyloid beta peptide (Abeta) into the brain causes cognitive
      impairment. We investigated whether prescription pre-administration of n-3 fatty
      acids improves cognitive learning ability in young rats and whether it protects
      against learning ability impairments in an animal model of Alzheimer's disease
      that was prepared by infusion of Abeta(1-40) into the cerebral ventricles of
      rats. Pre-administration of TAK-085 (highly purified and concentrated n-3 fatty
      acids containing eicosapentaenoic acid ethyl ester and docosahexaenoic acid ethyl
      ester) at 300 mg kg(-1) day(-1) for 12 weeks significantly reduced the number of
      reference memory errors in an 8-arm radial maze, suggesting that long-term
      administration of TAK-085 improves cognitive leaning ability in rats. After pre
      administration, the control group was divided into the vehicle and Abeta-infused
      groups, whereas the TAK-085 pre-administration group was divided into the TAK-085
      and TAK-085 + Abeta groups (TAK-085-pre-administered Abeta-infused rats). Abeta(1
      40) or vehicle was infused into the cerebral ventricle using a mini osmotic pump.
      Pre-administration of TAK-085 to the Abeta-infused rats significantly suppressed
      the number of reference and working memory errors and decreased the levels of
      lipid peroxide and reactive oxygen species in the cerebral cortex and hippocampus
      of Abeta-infused rats, suggesting that TAK-085 increases antioxidative defenses.
      The present study suggests that long-term administration of TAK-085 is a possible
      therapeutic agent for protecting against Alzheimer's disease-induced learning
      deficiencies.

PMID- 21894326
TI  - Cardioprotective properties of raw and cooked eggplant (Solanum melongena L).
AB  - Although eggplants are known to be part of a healthy diet, the effects of this
      fruit on cardioprotection are not known. The present study examined the role of
      raw and grilled eggplants on cardioprotection using an isolated perfusion heart
      model. The animals were fed freeze-dried products of either raw or grilled
      eggplants for 30 days. After 30 days, isolated working hearts were subjected to
      30 min ischemia followed by 2 h of reperfusion. Left ventricular function was
      monitored, and myocardial infarct size and cardiomyocyte apoptosis were assessed.
      To determine the antioxidant function of eggplants, their DPPH scavenging ability
      were determined, and polyphenolic components, especially nasunin content, were
      determined. The chemical composition of raw and grilled eggplants were determined
      in order to examine whether grilling was associated with major changes in their
      composition. The results of this study demonstrated eggplants as containing
      potent cardioprotective compounds judging by their ability to increase left
      ventricular function, and reduce myocardial infarct size and cardiomyocyte
      apoptosis. However, there was no difference in cardioprotective ability between
      the raw and grilled products. The antioxidant vitamins, including vitamin A,
      vitamin C and beta-carotene, were lower and some of the polyphenolic components,
      especially nasunin content, were higher in grilled eggplants, but they were
      unable to demonstrate better cardioprotective properties compared to the raw
      fruit.

PMID- 21894327
TI  - Raspberry juice consumption, oxidative stress and reduction of atherosclerosis
      risk factors in hypercholesterolemic golden Syrian hamsters.
AB  - The effects of raspberries on early atherosclerosis in Syrian hamsters were
      investigated using three juices prepared from var. Cardinal, Glen Ample and
      Tulameen berries. The hamsters received an atherogenic diet for 12 weeks and at
      the same time a juice at a daily dose corresponding to the consumption of 275 ml
      by a 70 kg human. A control group received the same diet with water instead
      juice. The principal polyphenolic compounds in the juices were anthocyanins and
      ellagitannins, which were present at concentrations of 218-305 MUg mL(-1) and 45
      72 MUg mL(-1), respectively. The three juices had similar but not identical
      effects. They all inhibited cardiac and aortic production of superoxide anion and
      increased hepatic glutathione peroxidase activity although only Tulameen juice
      brought about a significant increase in superoxide dismutase activity. Glen Ample
      was the only juice to significantly increase plasma paraoxonase activity. All the
      juices lowered plasma triglyceride level while consumption of Tulameen and
      Cardinal, but not Glen Ample, significantly lowered plasma total cholesterol and
      LDL-cholesterol. Cardinal was the sole juice to significantly increase HDL
      cholesterol and likewise it also significantly reduced body weight. These
      findings suggest that moderate consumption of raspberry juices can help to
      prevent the development of early atherosclerosis, with the underlying mechanisms
      related to improved antioxidant status and serum lipid profiles.

PMID- 21894328
TI  - Dietary vitamin K alleviates the reduction in testosterone production induced by
      lipopolysaccharide administration in rat testis.
AB  - Vitamin K is essential for the posttranslational modifications of blood
      coagulation factors and proteins present in the bone matrix. Vitamin K is
      distributed not only in the liver and bones but is also abundant in the brain,
      kidney, and gonadal tissues. However, the function of extra-hepatic/bone vitamin
      K has not been fully elucidated. Previously, we observed that dietary
      supplementation with vitamin K suppresses inflammation, and vitamin K deficiency
      decreases testicular testosterone production in rats. Here, we examined whether
      the dietary vitamin K state affects testicular steroidogenesis in
      lipopolysaccharide (LPS)-treated rats because vitamin K has anti-inflammatory
      activity. Male Wistar rats were fed either vitamin K-free or control diets for 35
      d, and then intraperitoneally administered LPS (0.5 mg kg(-1) body weight) to
      induce inflammation for 6 h. Vitamin K deficiency symptoms were not observed in
      the vitamin K-free diet group; however, the vitamin K levels in the testis were
      significantly lower in the vitamin K-free diet group than in the control diet
      group. After LPS treatment, plasma testosterone levels were significantly reduced
      in the vitamin K-free diet group compared with the control diet group. Testicular
      mRNA and protein levels of Cyp11a, a rate-limiting enzyme in steroidogenesis,
      corresponded to plasma testosterone levels. However, plasma luteinizing hormone
      levels were unaffected by diet and LPS. Phosphorylated nuclear factor kappaB p65
      in the testis was significantly increased in the LPS-treated, vitamin K-free diet
      group compared with control. These results indicate that dietary vitamin K
      affects testicular vitamin K levels and ameliorates the LPS-induced reduction in
      testicular testosterone synthesis. Testicular vitamin K might facilitate the
      inhibition of inflammation signal transduction and maintain steady levels of
      testosterone.

PMID- 21894329
TI  - Bioavailability of hop-derived iso-alpha-acids and reduced derivatives.
AB  - Iso-alpha-acids (IAA) and their reduced derivatives (dihydro-iso-alpha-acids
      (DHIAA) and tetrahydro-iso-alpha-acids (THIAA)) have been administered to Caco-2
      cell monolayers (30, 60, and 120 MUM) to investigate epithelial transport, in
      both absorptive and secretive directions. In addition, 25 mg kg(-1) IAA, DHIAA,
      and THIAA were applied to New Zealand white rabbits (+/-3-3.5 kg) in a single
      intravenous and oral dose. The most important pharmacokinetic parameters (C(max),
      t(max), half life, clearance, and AUC(0-infinity)) and the absolute
      bioavailability were determined for each class of hop acid. The results from the
      in vitro Caco-2 study of IAA, DHIAA, and THIAA, showed a higher membrane
      permeability for IAA and THIAA, both in absorptive (P(appAB) range 1.6-5.6 * 10(
      6) cm s(-1)) and secretive directions (P(appBA) range 5.7-16.3 * 10(-6) cm s(
      1)), when compared to DHIAA. Factors limiting transport of DHIAA could include
      phase II metabolism. After oral and i.v. dosing to New Zealand white rabbits, the
      absolute bioavailability for IAA was determined to be 13.0%. The reduced
      derivatives reached higher bioavailabilities with 28.0% for DHIAA and 23.0% for
      THIAA. The area under curve AUC(0-infinity) upon oral gavage for DHIAA and THIAA
      was 70.7 +/- 48.4 MUg h ml(-1) and 57.4 +/- 9.0 MUg h ml(-1), respectively, while
      that for IAA was 10.6 +/- 5.3 MUg h ml(-1). Phase I metabolism was indicated as
      the main factor limiting the bioavailability of IAA. Bioavailability of DHIAA is
      mostly influenced by phase-II metabolism as shown by enzymatic hydrolysis of
      plasma samples upon administration of DHIAA.

PMID- 21894330
TI  - New insights on the interaction mechanism between tau protein and oleocanthal, an
      extra-virgin olive-oil bioactive component.
AB  - Oleocanthal (OLC) is a phenolic component of extra-virgin olive oil, recently
      supposed to be involved in the modulation of some human diseases, such as
      inflammation and Alzheimer. In particular, OLC has been shown to abrogate
      fibrillization of tau protein, one of the main causes of Alzheimer
      neurodegeneration. A recent interpretation of this mechanism has been attempted
      on the basis of OLC reactivity with the fibrillogenic tau hexapeptide VQIVYK and
      SDS-PAGE of OLC/tau incubation mixtures, suggesting that covalent modification
      events modulate tau fibrillization. In this paper we report a detailed mass
      spectrometric investigation of the OLC reactive profile with both tau protein
      fibrillogenic fragment K18 and propylamine in biomimetic conditions. We show that
      K18 is prone to be covalently modified by OLC through Schiff base formation
      between the epsilon-amino group of lysine residues and OLC aldehyde carbonyls.
      Moreover, as expected from its de-structured conformation, K18 shows a non
      selective modification profile, reacting with several lysine residues to give
      cyclic pyridinium-like stable adducts. These data give new insights on the
      mechanism of inhibition of tau fibrillization mediated by OLC.

PMID- 21894331
TI  - Magnetic and thermal properties of three ionothermally synthesized metal
      carboxylate frameworks of [M3(ip)4][EMIm]2 (M = Co, Ni, Mn, H2ip = isophthalic
      acid, EMIm = 1-ethyl-3-methyl imidazolium).
AB  - Three metal-organic frameworks, [M(3)(ip)(4)][EMIm](2) (M = Co 1, Ni 2, Mn 3,
      H(2)ip = isophthalic acid, EMIm = 1-ethyl-3-methyl imidazolium) were prepared
      from an ionic liquid medium. All the compounds feature the same (4(24))(6(4))
      topology based on linear trinuclear clusters as eight-connected nodes. Compounds
      1 and 2 are isostructural, while compound 3 exhibits a different structure due to
      the slight difference in the arrangement of M(3)(OOCR)(8) SBUs. Magnetic property
      measurements reveal that all the compounds display anti-ferromagnetic coupling,
      where compounds 2 and 3 show isotropic exchange interactions of -0.10 cm(-1) for
      2 and -1.6 cm(-1) for 3. Investigation of the thermal diffusivity shows that the
      thermal diffusivity of 1 is higher than that of 3, while that of 3 is higher than
      that of 2.

PMID- 21894332
TI  - Acceptor (CF3)PCPH pincer reactivity with (PPh3)3Ir(CO)H.
AB  - The syntheses of Ir(I) and Ir(III) complexes incorporating the electron
      withdrawing pincer ligand (1,3-C(6)H(4)(CH(2)P(CF(3))(2))(2)) ((CF(3))PCPH) with
      (PPh(3))(3)Ir(CO)H and subsequent chemistry are reported. Under ambient
      conditions, reaction of 1 equiv. (CF(3))PCPH with (PPh(3))(3)Ir(CO)H gave the
      mono-bridged complex [Ir(CO)(PPh(3))(2)(H)](2)(MU-(CF(3))PCPH) (1). Reaction of
      (PPh(3))(3)Ir(CO)H with excess (CF(3))PCPH and MeI gave the doubly-bridged
      complex [Ir(CO)(PPh(3))(H)](2)(MU-(CF(3))PCPH)(2) (2), whereas the tetrameric
      oligomer [Ir(CO)(PPh(3))(H)](4)(MU-(CF(3))PCPH)(4) (2-sq) was obtained from a 1:1
      ligand:metal mixture in benzene in the presence of excess MeI. At higher
      temperatures (165  degrees C) the reaction of (CF(3))PCPH with (PPh(3))(3)Ir(CO)H
      afforded the 5-coordinate Ir(I) complex ((CF(3))PCP)Ir(CO)(PPh(3)) (3). Complex 3
      shows mild catalytic activity for the decarbonylation of 2-naphthaldehyde in
      refluxing diglyme (162  degrees C).

PMID- 21894333
TI  - A temperature-dependent order-disorder and crystallographic phase transition in a
      0D Fe(II) spin crossover compound and its non-spin crossover Co(II) isomorph.
AB  - The new dipyridylamino/triazine ligand DDE (N(2),N(2),N(4),N(4)-tetraethyl
      N(6),N(6)-di(pyridin-2-yl)-1,3,5-triazine-2,4,6-triamine) has been incorporated
      into the mononuclear Fe(II) SCO compounds cis-[Fe(II)(NCSe)(2)(DDE)(2)] (1), cis
      [Fe(II)(NCBH(3))(2)(DDE)(2)] (2), and cis-[Fe(II)(NCS)(2)(DDE)(2)] (3). Magnetic
      susceptibility measurements reveal that each of 1, 2 and 3 undergoes a complete,
      continuous spin transition with a T(1/2) of ~260 K, ~300 K and ~205 K,
      respectively. An analogue and isomorph of 1, cis-[Co(II)(NCSe)(2)(DDE)(2)] (4),
      remains high spin down to low temperatures. Variable temperature single crystal
      data reveal that 1 and 4 undergo a crystallographic phase transition (from
      orthorhombic Pbcn at high temperatures to monoclinic P2/c at low temperatures)
      accompanied by an order-disorder transition of ethyl moieties of the DDE ligand.
      In the Pbcn phase, the structures of 1 and 4 contain one crystallographically
      unique M(II) centre, while in the P2/c phase, 1 and 4 contain two
      crystallographically unique M(II) centres. Variable temperature powder X-ray
      diffraction experiments reveal that the crystallographic phase transition occurs
      at ~250 K for 1. The occurrence of the concomitant order-disorder and
      crystallographic phase transitions undergone by 1 and 4 is not directly apparent
      in their magnetic susceptibility measurements, and this is likely due to the
      local environment of the M(II) centres remaining largely undisturbed as the
      transitions occur. The compound 2 is isostructural to 1 and 4 at low
      temperatures.

PMID- 21894334
TI  - Synthesis and characterization of platinum(II) di-ynes and poly-ynes
      incorporating ethylenedioxythiophene (EDOT) spacers in the backbone.
AB  - A series of trimethylsilyl-protected di-alkynes incorporating 3,4
      ethylenedioxythiophene (EDOT) linker groups Me(3)Si-C=C-R-C=C-SiMe(3) (R =
      ethylenedioxythiophene-3,4-diyl 1a, 2,2'-bis-3,4-ethylenedioxythiophene-5,5'-diyl
      2a, 2,2',5',2''-ter-3,4-ethylenedioxythiophene-5,5''-diyl 3a) and the
      corresponding terminal di-alkynes, H-C=C-R-C=C-H 1b-2b has been synthesized and
      characterized and the single crystal X-ray structure of 1a has been determined.
      CuI-catalyzed dehydrohalogenation reaction between trans-[(Ph)(Et(3)P)(2)PtCl]
      and the terminal di-alkynes 1b-2b in (i)Pr(2)NH/CH(2)Cl(2) (2:1 mole ratio) gives
      the Pt(II) di-ynes trans-[(Et(3)P)(2)(Ph)Pt-C=C-R-C=C-Pt(Ph)(Et(3)P)(2)] 1M-2M
      while the dehydrohalogenation polycondensation reaction between trans
      [((n)Bu(3)P)(2)PtCl(2)] and 1b-2b (1:1 mole ratio) under similar reaction
      conditions affords the Pt(II) poly-ynes trans-[Pt(P(n)Bu(3))(2)-C=C-R-C=C-](n)1P
      2P. The di-ynes and poly-ynes have been characterized spectroscopically and, for
      1M and 2M, by single-crystal X-ray which confirms the "rigid rod" di-yne
      backbone. The materials possess excellent thermal stability, are soluble in
      common organic solvents and readily cast into thin films. Optical absorption
      spectroscopic measurements reveal that the EDOT spacers create stronger donor
      acceptor interactions between the platinum(II) centres and conjugated ligands
      along the rigid backbone of the organometallic polymers compared to the related
      non-fused and fused oligothiophene spacers.

PMID- 21894335
TI  - One-pot synthesis of pyrrolo[1,2-a]quinoxalines.
AB  - A transition metal-free process for the regioselective synthesis of pyrrolo[1,2
      a]quinoxalines under mild conditions in one-pot is described. The reaction
      afforded a variety of products in good to excellent yields. Indolo[1,2
      a]quinoxalines were also synthesized from indole-2-carboxamides under the same
      conditions.

PMID- 21894336
TI  - Applications of nanoscale carbon-based materials in heavy metal sensing and
      detection.
AB  - This article reviews applications of nanoscale carbon-based materials in heavy
      metal sensing and detection. These materials, including single-walled carbon
      nanotubes, multi-walled carbon nanotubes and carbon nanofibers among others, have
      unique and tunable properties enabling applications in various fields spanning
      from health, electronics and the environment sector. Specifically, we highlight
      the unique properties of these materials that enable their applications in the
      sorption and preconcentration of heavy metals ions prior to detection by
      spectroscopic, chromatographic and electrochemical techniques. We also discuss
      their distinct properties that enable them to be used as novel electrode
      materials in sensing and detection. The fabrication and modification of these
      electrodes is discussed in detail and their applications in various
      electrochemical techniques such as voltammetric stripping analysis,
      potentiometric stripping analysis, field effect transistor-based devices and
      electrical impedance are critically reviewed. Perspectives and futures trends in
      the use of these materials in heavy metal sensing and detection will also be
      highlighted.

PMID- 21894337
TI  - Gold/copper-catalyzed activation of the aci-form of nitromethane in the synthesis
      of methylene-bridged bis-1,3-dicarbonyl compounds.
AB  - Activation of the aci-form of nitromethane using Lewis acids for the attack of
      carbon nucleophiles was studied. 1,3-Dicarbonyl compounds in the presence of
      catalytic amounts of AuCl(3) or Cu(OTf)(2) in nitromethane solvent could be
      converted into methylene-bridged bis-1,3-dicarbonyl compounds.

PMID- 21894338
TI  - How does trimethylamine N-oxide counteract the denaturing activity of urea?
AB  - Trimethylamine N-oxide, TMAO, stabilizes globular proteins and is able to
      counteract the denaturing activity of urea. The mechanism of this counteraction
      has remained elusive up to now. A rationalization is proposed grounded on the
      same theoretical model used to clarify the origin of cold denaturation, and the
      denaturing activity of GdmCl versus the stabilizing one of Gdm(2)SO(4) [G.
      Graziano, Phys. Chem. Chem. Phys., 2010, 12, 14245-14252; G. Graziano, Phys.
      Chem. Chem. Phys., 2011, 13, 12008-12014]. The fundamental quantities are: (a)
      the difference in the solvent-excluded volume on passing from the N-state to the
      D-state, calculated in water and in aqueous osmolyte solution; (b) the difference
      in energetic attractions of the N-state and the D-state with the surrounding
      solvent molecules, calculated in water and in aqueous osmolyte solution. In
      aqueous 8 M urea + 4 M TMAO solution, the first quantity is so large and positive
      to counteract the second one that is large and negative due to preferential
      binding of urea molecules to the protein surface. This happens because aqueous 8
      M urea + 4 M TMAO solution has a volume packing density markedly larger than that
      of water, rendering the cavity creation process much more costly. The volume
      packing density increase reflects the strength of the attractions of water
      molecules with both urea and TMAO molecules. This mechanism readily explains why
      TMAO counteraction is operative even though urea molecules are preferentially
      located on the protein surface.

PMID- 21894339
TI  - Proteomic analysis of gemcitabine-induced drug resistance in pancreatic cancer
      cells.
AB  - Currently, the most effective agent against pancreatic cancer is gemcitabine
      (GEM), which inhibits tumor growth by interfering with DNA replication and
      blocking DNA synthesis. However, GEM-induced drug resistance in pancreatic cancer
      compromises the therapeutic efficacy of GEM. To investigate the molecular
      mechanisms associated with GEM-induced resistance, 2D-DIGE and MALDI-TOF mass
      spectrometry were performed to compare the proteomic alterations of a panel of
      differential GEM-resistant PANC-1 cells with GEM-sensitive pancreatic cells. The
      proteomic results demonstrated that 33 proteins were differentially expressed
      between GEM-sensitive and GEM-resistant pancreatic cells. Of these, 22 proteins
      were shown to be resistance-specific and dose-dependent in the regulation of GEM.
      Proteomic analysis also revealed that proteins involved in biosynthesis and
      detoxification are significantly over-expressed in GEM-resistant PANC-1 cells. In
      contrast, proteins involved in vascular transport, bimolecular decomposition, and
      calcium-dependent signal regulation are significantly over-expressed in GEM
      sensitive PANC-1 cells. Notably, both protein-protein interaction of the
      identified proteins with bioinformatic analysis and immunoblotting results showed
      that the GEM-induced pancreatic cell resistance might interplay with tumor
      suppressor protein p53. Our approach has been shown here to be useful for
      confidently detecting pancreatic proteins with differential resistance to GEM.
      Such proteins may be functionally involved in the mechanism of chemotherapy
      induced resistance.

PMID- 21894340
TI  - Glutathione radical cation in the gas phase; generation, structure and
      fragmentation.
AB  - Two different chemical methods have been used to form glutathione radical
      cations: (1) collision-induced dissociations (CIDs) of the ternary complex
      [Cu(II)(tpy)(M)](2+) (M = GSH, tpy = 2,2':6',2''-terpyridine) and (2) homolysis
      of the S-NO bond in protonated S-nitrosoglutathione. The radical cations, M(+),
      were trapped and additional CIDs were performed. They gave virtually identical
      CID spectra, suggesting a facile interconversion between initial structures prior
      to fragmentation. DFT calculations at the B3LYP/6-31++G(d,p) level of theory have
      been used to study interconversion between different isomers of the glutathione
      radical cation and to examine mechanisms by which these ions fragment. The N
      terminal alpha-carbon-centred radical cation, strongly stabilized by the
      captodative effect, is at the global minimum, which is 8.5 kcal mol(-1) lower in
      enthalpy than the lowest energy conformer of the S-centred radical cation. The
      barrier against interconversion is 18.1 kcal mol(-1) above the S-centred radical.

PMID- 21894341
TI  - Hypocrellin-B acetate as a fluorogenic substrate for enzyme-assisted cell
      photosensitization.
AB  - Photosensitizing molecules (PSs) undergo chemico-physical changes upon addition
      of suitable substituents, influencing both their photophysical properties and
      their ability to accumulate into cells. Once inside the cells, the modified PS
      acts as a fluorogenic substrate: the added substituent is removed by a specific
      enzyme, restoring the native PS in subcellular sensitive sites. We investigated
      the photophysical properties and interaction with HeLa cells of Hypocrellin-B
      (HypB), as native molecule and upon acetate-group addition (HypB-Ac). Chemical
      modification alters both absorption and fluorescence features of HypB;
      consequently, the dynamics of the enzyme hydrolysis of HypB-Ac can be monitored
      through restoring the native HypB spectral properties. At the cellular level,
      only the HypB emission signal was detected within 5 min of incubation with either
      HypB or HypB-Ac, allowing a direct comparison of the time courses of their
      intracellular accumulation. Plateau values were reached within 15 min of
      incubation with both compounds, the emission signals being significantly higher
      in HypB-Ac than in HypB treated cells. Consistently, imaging showed a rapid
      appearance of red fluorescence in the cytoplasm, with more abundant bright spots
      in HypB-Ac treated cells. Both compounds did not induce dark toxicity at
      concentrations up to 1 * 10(-6) M, while upon irradiation at 480 nm phototoxicity
      was significantly higher for cells exposed to HypB-Ac than for HypB-loaded cells.
      These findings suggest an improved efficacy of acetylated HypB to be internalized
      by cells through membrane trafficking, with a preferential interaction of the
      photoactive molecules on sensitive intracellular sites. After irradiation, in
      HypB-Ac treated cells, prominent disorganization of several cytoplasmic
      organelles such as the endoplasmic reticulum, Golgi apparatus, lysosomes,
      microfilaments and microtubules were observed.

PMID- 21894342
TI  - The Baylis-Hillman reaction: a novel concept for creativity in chemistry.
AB  - This tutorial review highlights the way in which the Baylis-Hillman reaction has
      been increasingly attracting the attention of synthetic and medicinal chemists;
      it not only helps in originating new ideas to create novel methodologies and
      molecules but also offers intellectual challenges to understand and address the
      present day needs in the areas of organic and medicinal chemistry.

PMID- 21894343
TI  - Synthetic mammalian gene networks as a blueprint for the design of interactive
      biohybrid materials.
AB  - Synthetic biology aims at the rational design and construction of devices,
      systems and organisms with desired functionality based on modular well
      characterized biological building blocks. Based on first proof-of-concept studies
      in bacteria a decade ago, synthetic biology strategies have rapidly entered
      mammalian cell technology providing novel therapeutic solutions. Here we review
      how biological building blocks can be rewired to interactive regulatory genetic
      networks in mammalian cells and how these networks can be transformed into open-
      and closed-loop control configurations for autonomously managing disease
      phenotypes. In the second part of this tutorial review we describe how the
      regulatory biological sensors and switches can be transferred from mammalian cell
      synthetic biology to materials sciences in order to develop interactive biohybrid
      materials with similar (therapeutic) functionality as their synthetic biological
      archetypes. We develop a perspective of how the convergence of synthetic biology
      with materials sciences might contribute to the development of truly interactive
      and adaptive materials for autonomous operation in a complex environment.

PMID- 21894344
TI  - Two novel Dy8 and Dy11 clusters with cubane [Dy4(MU3-OH)4]8+ units exhibiting
      slow magnetic relaxation behaviour.
AB  - Two unique octa- and hendeca-nuclear dysprosium(III) clusters incorporating
      [Dy(4)(MU(3)-OH)(4)](8+) cubane units have been synthesized with the 1,10
      phenanthroline-2,9-dicarbaldehyde dioxime (H(2)phendox) ligand and DyCl(3).6H(2)O
      or Dy(OAc)(3).4H(2)O. They are
      [Dy(8)(OH)(8)(phendox)(6)(H(2)O)(8)]Cl(2)(OH)(2).18H(2)O.18MeOH (1) and
      [Dy(11)(OH)(11)(phendox)(6)(phenda)(3)(OAc)(3)](OH).40H(2)O.7MeOH (2). Adjacent
      Dy(8) in 1 or Dy(11) in 2 motifs are packed by off-set pi-pi interactions of the
      aromatic rings on phendox(2-) to generate a 3D supramolecular architecture in the
      honeycomb topology and with 1D or 3D channels along the c-axis. Adsorption
      research shows that complex 1 has selective adsorption ability for H(2)O over
      small gas molecules (H(2), N(2), CO(2)). Complex 2 is stable upon the removal of
      guest molecules and the desolvated compound absorbed a considerable amount of
      CO(2). Furthermore, the oximes underwent hydrolysis to carboxylic acid and the
      resulting 1,10-phenanthroline-2,9-dicarboxylate link the dysprosium atoms to form
      a hendecanuclear cluster of 2. Magnetic studies reveal that both clusters exhibit
      slow magnetic relaxation behavior, expanding upon the recent reports of the pure
      4f type single-molecule magnets (SMMs).

PMID- 21894345
TI  - Regioselectivity in the ring opening of non-activated aziridines.
AB  - In this critical review, the ring opening of non-activated 2-substituted
      aziridines via intermediate aziridinium salts will be dealt with. Emphasis will
      be put on the relationship between the observed regioselectivity and inherent
      structural features such as the nature of the C2 aziridine substituent and the
      nature of the electrophile and the nucleophile. This overview should allow
      chemists to gain insight into the factors governing the regioselectivity in
      aziridinium ring openings (81 references).

PMID- 21894346
TI  - Preparation of TiO2 nanowires/nanotubes using polycarbonate membranes and their
      uses in dye-sensitized solar cells.
AB  - Track-etched polycarbonate (PC) membranes were used as a soft template to
      synthesize mesoporous TiO(2) for use in dye-sensitized solar cells (DSSCs). The
      Ti precursor infiltrated into the cylindrical confined spaces of PC membranes.
      Upon calcination at 500  degrees C, TiO(2) nanowires (15TNW) were obtained from
      PC with a 15 nm pore diameter, whereas TiO(2) nanotubes (50TNT and 100TNT) were
      generated from PC with 50 and 100 nm diameter pores, respectively. TNW and TNT
      were used as photoelectrodes in DSSCs employing a polymer electrolyte. The
      ranking of the cell efficiencies of the 200 nm thick TiO(2) films was 50TNT
      (1.1%) > 15TNW (0.8%) ? 100TNT (0.7%), which was mostly attributed to different
      amounts of dye adsorption due to different surface areas. These TNW and TNT films
      were further coated with the graft copolymer-directed mesoporous TiO(2) and were
      used as interfacial layers between the FTO glass and the 4 MUm thick
      nanocrystalline TiO(2) film. As a result, the order of energy conversion
      efficiency was 15TNW (5.0%) ? 50TNT (4.8%) > 100TNT (4.1%). The improved
      performance of 15TNW was due to a higher transmittance through the electrode and
      a longer electron lifetime for recombination. The DSSC performance was
      systematically investigated in terms of interfacial resistance and charge
      recombination using electrochemical impedance spectroscopy.

PMID- 21894347
TI  - Comprehensive quality evaluation of Fructus Schisandrae using electrospray
      ionization ion trap multiple-stage tandem mass spectrometry coupled with chemical
      pattern recognition techniques.
AB  - Electrospray ionization ion trap multiple-stage tandem mass spectrometry (ESI
      MS(n)) was used to evaluate Fructus Schisandrae of similar species (Schisandra
      chinensis (Turcz.) Baill. fruits and Schisandra sphenanthera Rehd. et Wils.
      fruits) and different growth characteristics (color, shape, etc.). The
      application of chemical pattern recognition in the ESI-MS(n) data analysis was
      carried out by principal component analysis (PCA), hierarchical cluster analysis
      (HCA) and linear discriminant analysis (LDA). Then the antioxidant activity of
      different Fructus Schisandrae samples were determined by an LC-ESI-MS method and
      ferric reducing antioxidant power (FRAP) assay. Using the ESI-MS(n) method
      coupled with chemical pattern recognition analysis and correlated with the
      antioxidant activity evaluation, the two similar species were successfully
      distinguished, thus improving the therapeutic safety and effectiveness. The
      superior characteristics of Schisandra chinensis (Turcz.) Baill. fruits were
      obtained and made the selection and breeding of Chinese medicine materials more
      scientific. This study indicates that ESI-MS(n) is a valuable tool for the
      authentication of botanical origin and can also be useful for the quality control
      of Chinese medicinal herbs.

PMID- 21894348
TI  - Structural reorganization renders enhanced metalloprotein stability.
AB  - The enhanced stability of a mesophilic metalloprotein was assessed using
      biophysical spectroscopies. Significant local structural interconversions during
      thermal insult account for a reorganization of the protein scaffold, without
      disturbing the active metal site. This cushioning mechanism is proposed to be a
      generic property of metalloproteins contributing to enhanced stability.

PMID- 21894350
TI  - A comparison between a new 2-dimensional digital on-screen tooth measurement
      method with direct measurements.
AB  - OBJECTIVE: To compare the accuracy and reproducibility of tooth measurements
      using newly developed software that gives 2-dimensional scanned images of dental
      setups with direct measurements using digital calipers. METHODS: This
      experimental study was performed at the Dental Laboratories of the Faculty of
      Dentistry, University of Jordan, Amman, Jordan from September 2010 to December
      2010. Ten sets of acrylic teeth (10 upper and 10 lower arches) were used. The
      mesiodistal width of each individual tooth was measured using a digital caliper
      (method I), which was considered the gold standard. The teeth were set to create
      20 dental setups. The mesiodistal widths of teeth on the created setups were then
      measured by using a digital caliper (method II). The dental setups were then
      scanned using a flatbed computer scanner and tooth width measurements were
      performed using a special computer program (method III). Tooth measurements were
      divided into 6 groups, and the 3 methods were compared. RESULTS: There was a
      statistical significant difference between the 3 measurement methods in most of
      the measured tooth groups. Methods I and II exhibited significant differences for
      most of tooth groups (ranged from 0.02 to 0.22 mm) while no significant
      difference was found between methods I and III (ranged from 0.03 to 0.11 mm).
      CONCLUSION: Tooth width measurement with on-screen 2-dimensional scanned images
      of dental casts is comparable to measurements obtained using direct digital
      caliper.

PMID- 21894349
TI  - Survival and long-term neurodevelopmental outcome of the extremely preterm
      infant. A systematic review.
AB  - Survival rates among live births in North American tertiary perinatal centers
      since 1990 were 28% at 23 weeks, 52% at 24, 70% at 25 and 83% at 26 weeks.
      However, there is wide variation among centers. Survival rates in 2010 among
      tertiary centers in the United States participating in the Vermont-Oxford Network
      were 34% at 23 weeks, 61% at 24, 79% at 25, and 87% at 26. All reports of
      neurodevelopmental outcome of extremely preterm infants in the English literature
      were reviewed. This literature is very heterogeneous and prevalence highly
      variable. Major limitations are astonishing variation in criteria for major
      disability and that, even with the same disability criteria, children with major
      disabilities are functionally very heterogeneous. Mean prevalence of disability
      in the literature is 36%, but ranges from 10-61%. This literature could be
      improved if survivors were followed until early school age, there were more
      uniform reporting by week of gestation, and outcomes of term control groups were
      included.

PMID- 21894351
TI  - Medial open reduction of developmental dysplasia of the hip using the Weinstein
      Ponseti approach.
AB  - OBJECTIVE: To evaluate the efficacy and safety of medial open reduction using the
      Weinstein-Ponseti approach to treat developmental dysplasia of the hip (DDH).
      METHODS: In this retrospective study, 35 hips were treated in 24 children (one
      boy and 23 girls, mean age 10.8+/-2.82 months, range 6-16 months) in the
      Department of Orthopedic Surgery, Medical Faculty, Harran University, Sanliurfa,
      Turkey, between April 1997 and February 2009. We evaluated radiologically the
      patient's hip pre-operatively using the Tonnis grading system and acetabular
      index. Group 1 included 13 patients aged younger than 12 months (19 hips) and
      Group 2 included 11 patients aged 12 months or older (16 hips). Clinical and
      radiographic evaluations were made according to the McKay and Severin's criteria,
      respectively. Avascular necrosis (AVN) was evaluated according to the Kalamchi
      and Mac Ewen's classification. RESULTS: The average follow-up period was 5.6 +/
      3.1 years (range, 2-12 years). Five hips (14.2%) required a second procedure.
      Avascular necrosis was observed in 6 hips (17.1%). Clinical and radiological
      assessments showed that the outcome was not significantly different between the 2
      groups. Furthermore, after this follow up period, the rates of AVN were similar.
      CONCLUSION: Analyzing retrospectively after comparison of this method before and
      after the age of 12 months, we found no difference between the 2 groups. Children
      with DDH can be successfully treated by this method up to 16 months.

PMID- 21894352
TI  - Pattern of relapse after curative surgery for metastatic colorectal cancer.
AB  - OBJECTIVE: To investigate patterns in the relapse frequency after curative
      surgical intervention, with the intention of determining the feasibility of a
      complete holiday from chemotherapy for metastatic colorectal cancer (mCRC)
      patients. METHODS: Patients with stage IV mCRC who received curative surgical
      intervention between January 1999 and December 2009 at Changhua Christian
      Hospital, Changhua, Taiwan were investigated retrospectively. Factors influencing
      the frequency and pattern of relapse were analyzed by logistic regression.
      Factors influencing overall survival (OS) were analyzed with Cox proportional
      hazard ratios. Significant factors were extracted and relationships to OS were
      evaluated by Kaplan-Meier with Log-Rank test. RESULTS: One hundred and thirty-two
      patients were included in the study in which 94 (71.2%) suffered from relapse.
      The number of relapses peaked between 3 and 6 months. The incidence of relapse
      and Disease-free survival had a negative influence on OS, with a hazard ratio
      (HR) of 0.36 (95% CI: 0.01-0.26) and 0.93 (95% CI: 0.90-0.95). The prognosis was
      significantly worse when the relapse (n=25) occurred within 6 months after
      metastectomy (p<0.001). Patients exhibited significantly better long-term OS if
      the relapse does not occur within 28 months after surgery (p<0.001). CONCLUSION:
      Early relapse indicated a worse prognosis. We determined that if mCRC patients
      remain cancer-free for 28 months after curative surgery, their chance of long
      term survival is significantly better.

PMID- 21894353
TI  - Conservative treatment of ovarian cancer. Safety, ovarian function preservation,
      reproductive ability, and emotional attitude of the patients in Saudi Arabia.
AB  - OBJECTIVE: To evaluate the safety, ovarian function preservation, reproductive
      ability, and the emotional attitude after a conservative surgery for ovarian
      cancer. METHODS: This is a retrospective study of women conservatively treated
      for primary ovarian cancer between January 2000 and December 2010 at King
      Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia. Patient's charts
      were reviewed for pathology, stage, requirement of adjuvant chemotherapy, and
      recurrent, as well as menstrual history, and pregnancy after treatment. During
      follow up the patients were asked 3 questions about their emotional attitude
      toward their disease. RESULTS: There were 39 patients identified (mean age 22
      years). Thirty-one (80%) patients were presented with stage I and 20 (52%) were
      Germ cell tumor. Fifteen (39%) patients received initial chemotherapy after
      primary surgery. Three (8%) patients had recurrent. Thirty-eight (98%) patients
      retuned to a regular menstruation after treatment. Eight patients (20%) had a
      normal pregnancy. Of the respondents to the given questions, 10 (44%) patients
      claimed that their disease did not have any impact on their desire to have
      children and 12 patients (52%) feared that their ovarian disease could have
      damage in their reproductive potential. Only 9 patients (39%) had no concerned
      about the effect of the treatment they received on the offspring. CONCLUSION:
      Fertility sparing surgery in ovarian cancer appears to be safe, and a practical
      treatment option in selected cases with ovarian cancer diagnosis. Most patients
      can have ovarian preservation after treatment and should not be discouraged from
      getting pregnant.

PMID- 21894354
TI  - Subclinical atherosclerosis in obese adolescents with normal left ventricular
      function.
AB  - OBJECTIVE: To assess the impact of obesity on carotid intima media thickness and
      left ventricular (LV) mass in obese adolescents. METHODS: The study included 52
      obese adolescents (mean age 14.16+/-2.64 years) and 52 healthy adolescents who
      served as a control group (mean age 12+/-2.3 years), who were attended the
      outpatient clinic at Suez Canal University Hospital, Ismailia, Egypt. The study
      population was submitted for medical history, clinical examination, laboratory
      investigations (fasting blood sugar and lipid profile), and echocardiographic
      examination of LV mass and dimensions. Assessment of carotid intima-media
      thickness was carried out by using carotid duplex. All children had normal LV
      function. RESULTS: Obese adolescents had a significant increase in total
      cholesterol, triglyceride, LDL-C, and low HDL-C compared to the control group.
      Also, there was a significant increase in blood pressure, carotid intima media
      thickness, LV mass, and LV mass index. There was a significant correlation
      between BMI and dyslipidemia, blood pressure, carotid intima/media thickness, LV
      mass, and posterior wall thickness. Carotid intima-media thickness had a
      significant correlation with increased LDL-C and low HDL-C, blood pressure, LV
      mass, and posterior wall thickness. CONCLUSION: Obesity in childhood and
      adolescents is associated with subclinical atherosclerosis. Although obese
      children had no LV dysfunction, yet there are LV structure changes.

PMID- 21894355
TI  - The relation between vitamin D deficiency and fibromyalgia syndrome in women.
AB  - OBJECTIVE: To define the relationship between vitamin D deficiency and
      fibromyalgia syndrome. METHODS: This is a prospective cohort study for
      description of a medical disorder. The study was carried out in Sultan Bin
      Abdulaziz Humanitarian City, Riyadh, Kingdom of Saudi Arabia from May 2007 to
      March 2010. One hundred women suffering from fibromyalgia syndrome were included.
      Blood level of 25-hydroxyvitamin D [25(OH) D] was estimated at initial visit and
      every 4 weeks until its level exceeded 50 ng/mL. The patients with vitamin D
      deficiency were treated with ergocalciferol 50,000 IU once weekly until their
      blood level of 25(OH) D exceeded 50 ng/mL. The number of tender points and the
      revised Fibromyalgia Impact Questionnaire (FIQR) score were used to assess the
      fibromyalgia before and after vitamin D repletion. RESULTS: Among the 100
      fibromyalgia women, there were 61 women with 25(OH) D deficiency; with vitamin D
      supplementation, only 42 women showed a significant improvement when their blood
      level of 25(OH) D became>or=30 ng/mL, this improvement became more significant
      when their blood level of 25(OH) D exceeded 50 ng/ mL. CONCLUSION: Vitamin D
      deficiency has to be considered in the management of fibromyalgia syndrome.

PMID- 21894356
TI  - Age-specific reference range for serum prostate-specific antigen in Sudanese men.
AB  - OBJECTIVE: To determine age-specific prostate-specific antigen (PSA) reference
      values in a community-based sample of Sudanese men, aged 40-90 years. METHODS:
      This study was conducted in the Central Laboratory Services, Soba University
      Hospital, Khartoum, Sudan from January 2008 to May 2010. Total serum PSA in 3475
      Sudanese men with no clinical evidence of lower urinary tract symptoms were
      measured using immunoenzometric assay. Out of the 3475, only 1051 men met the
      inclusion criteria. Those with total PSA<10 ng/ml and no recent urinary tract
      infection were included in this study. The data were analyzed using SPSS for
      Windows to define age-specific reference ranges of PSA. RESULTS: The geometric
      mean of total serum PSA in the study group of Sudanese men was 1.48 ng/ml. The
      95th percentile total serum PSA ranges in the age groups was 0-3 ng/ml for 40-49
      years, 0-3.02 ng/ml for 50-59 years, 0-3.8 ng/ml for 60-69 years and 0-8.7 ng/ml
      for 70-90 years. CONCLUSION: The currently adopted age-specific total PSA
      reference ranges are not appropriate for Sudanese men. Accordingly, our study
      indicates that the reference ranges of this study may be more suitable.

PMID- 21894357
TI  - Impact of pH1N1 influenza A infections on the Otolaryngology, Head and Neck
      Clinic during Hajj, 2009.
AB  - OBJECTIVE: To examine the possible implications of the 2009 H1N1 influenza A
      (pandemic flu, pH1N1) on this religious gathering and provide a response plan for
      the Otolaryngology, Head and Neck (ENT) clinic during the Hajj pilgrimage.
      METHODS: This study was conducted between November and December 2009. All
      patients presenting to the ENT clinic at Al-Noor Specialist Hospital, Makkah,
      Kingdom of Saudi Arabia were recorded. Descriptive statistics were used to
      analyze the data. RESULTS: A total of 3087 patients were included (mean age 35+/
      7.8 years), of which, 2114 were males (68.5%), and 973 females (31.5%, male to
      female gender ratio=2.17:1). Among them, 1467 patients (47.5%) were Hajji and
      1620 patients (52.5%) were non-Hajji. Saudi patients comprised 1602 (51.8%),
      while non-Saudi's comprised 1485 (48.2%). Upper respiratory tract infections
      (URTI) including the diagnosis of pharyngitis, viral URTI, pH1N1, and tonsillitis
      represented (92%) of total diagnoses. Of these, only 77 suspected pH1N1 cases
      (2.5%) were observed in the ENT clinic. Management of 3045 patients (98.6%)
      included antimicrobials as part of their main therapy. CONCLUSION: The pH1N1
      cases presenting to our ENT Hajj clinic had a minimal impact on the clinic
      operation. The ENT Hajj Clinic helped alleviate pressure from the ER. Excessive
      use of antibiotic usage should be discouraged.

PMID- 21894358
TI  - Role of selected simple non-invasive laboratory investigations in assessing
      functional abdominal pain in children aged 5-15 years in Khartoum, Sudan.
AB  - OBJECTIVE: To determine simple laboratory test in children with functional
      abdominal pain, to compare this test in those with functional abdominal pain in
      normal children and to try to search for it cause if any, and to determine the
      symptoms and signs of the disease. METHODS: This study was carried out over a
      period of 3 years, from March 2007 to February 2010 at Gaffar Ibn Auf Specialized
      Hospital for Children, Khartoum, Sudan. The study was conducted to determine role
      of simple investigations for functional abdominal pain (FAP) in a group of 35
      children with abdominal pain and compared it to the control group (42 children)
      with an age range of 4-15 years. RESULTS: The results showed no parasitic, no
      urinary track infection, no Helicobacter pylori infection association with
      functional abdominal pain. However, gender, socioeconomic status, weight >50th
      centile had a significant association with functional abdominal pain. CONCLUSION:
      Functional abdominal pain is very confusing and puzzling condition to doctors,
      parents, and patients. Establishment of centers for medical education regarding
      this cause of abdominal pain is needed.

PMID- 21894359
TI  - Ulcerative colitis in children and adolescents from the Western Region of Saudi
      Arabia.
AB  - OBJECTIVE: To examine the clinical pattern of pediatric ulcerative colitis (UC)
      at King Abdul-Aziz University Hospital, Jeddah, Saudi Arabia. METHODS: In this
      retrospective study, we collected data from the medical and endoscopy records of
      pediatric ulcerative colitis patients between January 2001 and March 2010. The
      study took place in the Department of Pediatrics, Faculty of Medicine and King
      Abdul-Aziz University Hospital, King Abdul-Aziz University, Jeddah, Kingdom of
      Saudi Arabia. RESULTS: Fifty-seven patients were investigated with mean age+/-SD
      at diagnosis of 8.8+/-4.9 years. The study population comprised of 54 (59.6%)
      females and 42 (73.7%) males. The most common symptoms identified were abdominal
      pain (93%), rectal bleeding (93%), and diarrhea (86%). The extra-intestinal
      manifestations were observed in some patients (7%), and 2 (3.5%) had family
      history of first-degree relatives with inflammatory bowel disease (IBD). The
      anatomical extent of UC was severe in 77.2%, left sided in 12.3%, and distal in
      10.5%. The endoscopic assessment of mucosal inflammation was graded as moderate
      to severe. The disease pattern included chronic relapse type (50.9%), initial
      onset type (40.4%), and chronic continuous type with intermittent exacerbation
      (8.8%). Laboratory results demonstrated the following symptoms such as anemia
      (86%), thrombocytosis (74.4%), hypoalbuminemia (54.4%), high erythrocyte
      sedimentation rate (83%) and high C-reactive protein (77.8%). CONCLUSION: The
      incidence of UC in the western region of Saudi was found to be similar with
      reports from the Western population. Pediatricians should be conscious of such
      manifestations with early referral to specialized centers in order to avoid
      unnecessary delay in diagnosis and complications.

PMID- 21894360
TI  - Screening of depression among patients in Family Medicine in Southeastern Saudi
      Arabia.
AB  - OBJECTIVE: To determine the prevalence rate of depression and its relationship
      with patients' socio-demographic characteristics and chronic diseases. METHODS:
      This cross sectional study was performed at the Family Medicine Department,
      Sharurah Armed Forces Hospital (SAFH), Sharurah, Kingdom of Saudi Arabia. Two
      hundred and eighty adult subjects were randomly selected. Patient Health Outcomes
      9 Symptom Checklist was used for screening of depression in each participant.
      Also, information on socio-demographic characteristics and chronic diseases was
      collected. The field work was conducted between December 2010 to January 2011 and
      the study was completed in March 2011. RESULTS: Out of the 280 patients, 272
      responded to the questionnaires with a response rate of 97%. The total number of
      males was 116 (42.6%) and females was 156 (57.4%). Depression was diagnosed in
      12% (n=33) of screened population. Out of 33 depressed patients, 7 (21%) had
      minimal depression, 18 (55%) suffered from mild depression, 3 (9%) with moderate
      depression, 3 (9%) with moderately severe depression, and 2 (6%) with severe
      depression. The subjects who were living in a room were 4.8 times more likely to
      suffer from depression than subjects who stayed in a flat or villa. Also,
      employees were 1.7 times more prone to depression than non-working subjects.
      CONCLUSION: Depression is a common health problem among primary health care
      patients. Primary health care physicians should be the cornerstone in screening
      for an underlying depressive disorder and initiating appropriate referral or
      treatment.

PMID- 21894361
TI  - Effect of quality of life improvement on type 2 diabetes patients' self-esteem.
AB  - OBJECTIVE: To study the effects of the quality of life (QoL) improvement on their
      QoL and self-esteem. METHODS: This was a random controlled clinical trial study
      on 123 type 2 diabetes patients admitted to the Diabetes Clinic in Imam Khomeini
      Hospital at Ardebil, Iran from April 2009 to June 2010. The 30-70 years old
      participants are afflicted with type 2 diabetes, and randomly divided into 2
      groups (experimental group n=61, and control group n=62). The questionnaires were
      composed of sociodemographic status, Farrel & Grant, and Rosenberg's self-esteem
      questionnaires and the quality of life (QoL) improvement plan was codified to
      educate and evaluate them. A p<0.05 was considered significant. RESULTS: Our
      study showed that subjects in the experimental group had low self-esteem (13%)
      before QOL training, and they had moderate self-esteem after the intervention
      (39%), however, the control group had moderate self-esteem (62.5%) in the pre
      test, and changed to low self-esteem (12.9%) in the post-test, and there was
      significant difference in the previous and next intervention (p<0.05).
      CONCLUSION: The QoL improvement had positive effects on diabetic's self-esteem,
      and QOL as improved may help to reduce the side effects of type 2 diabetes
      process.

PMID- 21894362
TI  - Extraskeletal osteosarcoma, telangiectatic variant arising from the small bowel
      mesentery.
AB  - Extraskeletal osteosarcoma (EOS) is a highly aggressive and rare malignant soft
      tissue tumor, characterized by the production of neoplastic osseous tissue
      without attachment to the bone or periosteum. It rarely involves the visceral
      organs. Only 3 cases of mesenteric EOS have been reported in English literature.
      Here, we describe a male patient of 40 years, who was diagnosed to have EOS
      arising from small bowel mesentery. This patient presented with lower
      gastrointestinal (GI) bleeding. Upper GI endoscopy and colonoscopy were normal.
      Computed tomography scan demonstrated a well defined multi-loculated mixed
      density mass lesion measuring about 13x7x7 cm in lower abdomen adjacent to small
      bowel loops with liver metastasis. Palliative en bloc resection of tumor with
      adjacent small bowel was performed. The histopathology revealed a telangiectatic
      type osteosarcoma of mesentery. Diagnosis of EOS, its management and the outcome
      in context of the current literature are discussed.

PMID- 21894363
TI  - Rehabilitation medicine in the Kingdom of Saudi Arabia.

PMID- 21894364
TI  - The prevalence of vitamin D deficiency among female college students at Qatar
      University.

PMID- 21894365
TI  - Vancomycin-resistant Enterococci. Prevalence and risk factors for fecal carriage
      in patients at tertiary care hospitals.

PMID- 21894366
TI  - Acute life threatening events associated with hypocalcemia and vitamin D
      deficiency in early infancy. A single center experience from the Kingdom of Saudi
      Arabia.

PMID- 21894367
TI  - Hand hygiene compliance rate among healthcare professionals.

PMID- 21894368
TI  - The decision of do not resuscitate in pediatric practice.

PMID- 21894370
TI  - A comparative evaluation of end-emic and non-endemic region of visceral
      leishmaniasis (Kala-azar) in India with ground survey and space technology.
AB  - In visceral leishmaniasis, phlebotomine vectors are targets for control measures.
      Understanding the ecosystem of the vectors is a prerequisite for creating these
      control measures. This study endeavours to delineate the suitable locations of
      Phlebotomus argentipes with relation to environmental characteristics between
      endemic and non-endemic districts in India. A cross-sectional survey was
      conducted on 25 villages in each district. Environmental data were obtained
      through remote sensing images and vector density was measured using a CDC light
      trap. Simple linear regression analysis was used to measure the association
      between climatic parameters and vector density. Using factor analysis, the
      relationship between land cover classes and P. argentipes density among the
      villages in both districts was investigated. The results of the regression
      analysis indicated that indoor temperature and relative humidity are the best
      predictors for P. argentipes distribution. Factor analysis confirmed breeding
      preferences for P. argentipes by landscape element. Minimum Normalised Difference
      Vegetation Index, marshy land and orchard/settlement produced high loading in an
      endemic region, whereas water bodies and dense forest were preferred in non
      endemic sites. Soil properties between the two districts were studied and
      indicated that soil pH and moisture content is higher in endemic sites compared
      to non-endemic sites. The present study should be utilised to make critical
      decisions for vector surveillance and controlling Kala-azar disease vectors.

PMID- 21894371
TI  - Comparison of spoligotyping, mycobacterial interspersed repetitive units typing
      and IS6110-RFLP in a study of genotypic diversity of Mycobacterium tuberculosis
      in Delhi, North India.
AB  - The aim of the present study was to compare polymerase chain reaction (PCR)-based
      methods--spoligotyping and mycobacterial interspersed repetitive units (MIRU)
      typing--with the gold-standard IS6110 restriction fragment length polymorphism
      (RFLP) analysis in 101 isolates of Mycobacterium tuberculosis to determine the
      genetic diversity of M. tuberculosis clinical isolates from Delhi, North India.
      Spoligotyping resulted in 49 patterns (14 clusters); the largest cluster was
      composed of Spoligotype International Types (SITs)26 [Central-Asian (CAS)1-Delhi
      lineage], followed by SIT11 [East-African-Indian (EAI) 3-Indian lineage]. A large
      number of isolates (75%) belonged to genotypic lineages, such as CAS, EAI and
      Manu, with a high specificity for the Indian subcontinent, emphasising the
      complex diversity of the phylogenetically coherent M. tuberculosis in North
      India. MIRU typing, using 11 discriminatory loci, was able to distinguish between
      all but two strains based on individual patterns. IS6110-RFLP analysis (n = 80
      strains) resulted in 67 unique isolates and four clusters containing 13 strains.
      MIRUs discriminated all 13 strains, whereas spoligotyping discriminated 11
      strains. Our results validate the use of PCR-based molecular typing of M.
      tuberculosis using repetitive elements in Indian isolates and demonstrate the
      usefulness of MIRUs for discriminating low-IS6110-copy isolates, which accounted
      for more than one-fifth of the strains in the present study.

PMID- 21894372
TI  - Early detection of leprosy by examination of household contacts, determination of
      serum anti-PGL-1 antibodies and consanguinity.
AB  - A cross-sectional clinical trial in which the serum anti-phenolic glycolipid
      (anti-PGL-1) antibodies were analysed in household contacts (HHC) of patients
      with leprosy as an adjunct early leprosy diagnostic marker was conducted. The
      families of 83 patients underwent clinical examination and serum anti-PGL1
      measurement using enzyme-linked immunosorbent assay. Of 320 HHC, 98 were contacts
      of lepromatous leprosy (LL), 80 were contacts of borderline lepromatous (BL), 28
      were contacts of borderline (BB) leprosy, 54 were contacts of borderline
      tuberculoid (BT), 40 were contacts of tuberculoid (TT) and 20 were contacts of
      indeterminate (I) leprosy. Consanguinity with the patients was determined for 232
      (72.5%) HHC. Of those 232 contacts, 183 had linear consanguinity. Forty-nine HHC
      had collateral consanguinity. Fifty-eight contacts (18.1%) tested positive for
      anti-PGL1 antibodies. The number of seropositive contacts based on the clinical
      forms of the index case was 17 (29.3%) for LL, 15 (25.9%) for BL, one (1.7%) for
      BB, 14 (24.1%) for BT, three (5.2%) for TT and eight (13.7%) for I. At the one
      year follow-up, two (3.4%) of these seropositive contacts had developed BT
      leprosy. The results of the present study indicate that the serum anti-PGL-1 IgM
      antibody may be useful for evaluating antigen exposure and as a tool for an early
      leprosy diagnosis in HHC.

PMID- 21894373
TI  - Projecting the effectiveness of RotaTeq(r) against rotavirus-related
      hospitalisations in Brazil.
AB  - RotaTeq(r) (Merck & Company, Inc, Whitehouse Station, NJ, USA) is an oral
      pentavalent rotavirus vaccine (RV5) that has shown high and consistent efficacy
      in preventing rotavirus gastroenteritis (RGE) in randomised clinical trials
      previously conducted in industrialised countries with high medical care
      resources. To date, the efficacy and effectiveness data for RV5 are available in
      some Latin American countries, but not Brazil. In this analysis, we projected the
      effectiveness of RV5 in terms of the percentage reduction in RGE-related
      hospitalisations among children less than five years of age in four regions of
      Brazil, using a previously validated mathematical model. The model inputs
      included hospital-based rotavirus surveillance data from Goiania, Porto Alegre,
      Salvador and Sao Paulo from 2005-2006, which provided the proportions of
      rotavirus attributable to serotypes G1, G2, G3, G4 and G9, and published
      rotavirus serotype-specific efficacy from the Rotavirus Efficacy and Safety
      Trial. The model projected an overall percentage reduction of 93% in RGE-related
      hospitalisations, with an estimated annual reduction in RGE-related
      hospitalisations between 42,991-77,383 in the four combined regions of Brazil.
      These results suggest that RV5 could substantially prevent RGE-related
      hospitalisations in Brazil.

PMID- 21894374
TI  - A transient increase in total head phosphotyrosine levels is observed upon the
      emergence of Aedes aegypti from the pupal stage.
AB  - Phosphorylation and dephosphorylation of protein tyrosine residues constitutes a
      major biochemical regulatory mechanism for the cell. We report a transient
      increase in the total tyrosine phosphorylation of the Aedes aegypti head during
      the first days after emergence from the pupal stage. This correlates with an
      initial reduction in total head protein tyrosine phosphatase (PTP) activity.
      Similarly, phosphotyrosine (pTyr)-containing bands are seen in extracts prepared
      from both male and female heads and are spread among a variety of structures
      including the antennae, proboscis and the maxillary palps combined with the
      proboscis. Also, mosquitoes treated with sodium orthovanadate, a classical PTP
      inhibitor, show reduced blood-feeding activity and higher head tyrosine
      phosphorylation levels. These results suggest that pTyr-mediated signalling
      pathways may play a role in the initial days following the emergence of the adult
      mosquito from the pupal stage.

PMID- 21894375
TI  - Raphidascaris (Sprentascaris) lanfrediae sp. nov. (Nematoda: Anisakidae) from the
      fish Satanoperca jurupari (Osteichthyes: Cichlidae).
AB  - Raphidascaris (Sprentascaris) lanfrediae sp. nov. is described from the intestine
      of the freshwater fish Satanoperca jurupari (Heckel) (Cichlidae) from the Guama
      River, state of Para, Brazil. The prevalence in fish (n = 59) was 27% with
      intensity of one-124 (mean 16) nematodes per fish. The new species is
      characterized mainly by the markedly larger size of ventricular appendix in
      relation to the oesophagus, presence of short male caudal alae, 14-16 subventral
      pairs of preanal papillae and six pairs of postanal papillae.

PMID- 21894377
TI  - Plasmodium falciparum gametocyte carriage, emergence, clearance and population
      sex ratios in anaemic and non-anaemic malarious children.
AB  - Anaemia in falciparum malaria is associated with an increased risk of gametocyte
      carriage, but its effects on transmission have not been extensively evaluated in
      malarious children. Plasmodium falciparum gametocyte carriage, emergence,
      clearance, population sex ratios (SR) (defined as the proportion of gametocytes
      that are male), inbreeding rates and temporal changes in SR were evaluated in 840
      malarious children. Gametocyte carriage pre-treatment was at a level of 8.1%.
      Anaemia at enrolment was an independent risk factor for gametocyte carriage post
      treatment. The emergence of gametocytes seven days post-treatment was
      significantly more frequent in anaemic children (7/106 vs. 10/696, p = 0.002). In
      the initially detected gametocytes, the proportion of children with a male-biased
      SR (MBSR) (> 0.5) was significantly higher in anaemic children (6/7 vs. 3/10, p =
      0.027). Pre-treatment SR and estimated inbreeding rates (proportion of a mother's
      daughters fertilised by her sons) were similar in anaemic and non-anaemic
      children. Pre-treatment SR became more female-biased in non-anaemic children
      following treatment. However, in anaemic children, SR became male-biased. Anaemia
      was shown to significantly increase gametocyte emergence and may significantly
      alter the SR of emerging gametocytes. If MBSR is more infective to mosquitoes at
      low gametocytaemia, then these findings may have significant implications for
      malaria control efforts in endemic settings where malaria-associated anaemia is
      common.

PMID- 21894376
TI  - Myxidium volitans sp. nov., a parasite of the gallbladder of the fish,
      Dactylopterus volitans (Teleostei: Triglidae) from the Brazilian Atlantic coast-
      morphology and pathology.
AB  - Myxidium volitans sp. nov. (Myxozoa: Myxidiidae) parasitizing the hypertrophied
      green-brownish gallbladder of the teleost Dactylopterus volitans, collected in
      the Atlantic coast near Niteroi, Brazil was described based on ultrastructural
      studies. The spores were fusiform, sometimes slightly crescent-shaped on average
      21.7 +/- 0.3 um (mean +/- standard deviation) (n = 50) long and 5.6 +/- 0.4 um (n
      = 30) wide. The spore wall was thin and smooth, comprising two equally-sized
      valves joined by a hardly visible sutural ridge. Spores containing two pyriform
      polar capsules (PC) (5.0 +/- 0.4 * 2.3 +/- 0.3 um) (n = 30) are situated in each
      extremity of the spore. The PC wall was composed of hyaline layer (0.20-0.29 um
      thick) and by a thin external granular layer. Each PC contains a polar filament
      (PF) with irregular arrangements that was projected from its apical region to the
      bases of PC and coiled laterally from bases to the tip of PC. Some regular
      striations and S-like structures in the periphery of the PFs with four-five
      irregular sections were observed. Based on the spore morphology, ultrastructural
      differences and the specificity of the host we describe this parasite as a new
      myxosporidian, named M. volitans sp. nov.

PMID- 21894378
TI  - Specificity of immunoblotting analyses in eosinophilic meningitis.
AB  - Angiostrongylus cantonensis and Gnathostoma spinigerum are the two most common
      causative parasites of eosinophilic meningitis (EOM). Serological tests are
      helpful tools for confirming the identity of the pathogen. Recent reports
      determined the specificity of such tests by using normal healthy controls. There
      have been limited studies done to rule out the cross-reactivity between these two
      causative parasites of EOM. This study aims to assess the specificity of the
      serological test in EOM by using each condition as a control for the other.
      Thirty-three patients with a diagnosis of EOM were enrolled. Sera from 22
      patients with a positive 29-kDa antigenic diagnostic band of A. cantonensis were
      tested for the 21 and 24-kDa antigenic bands of G. spinigerum. Similarly, sera of
      11 gnathostomiasis patients were tested for the 29-kDa diagnostic band for A.
      cantonensis. Only one patient in the angiostrongyliasis group had a positive
      result for the 21 and 24-kDa antigenic bands of G. spinigerum, while no
      gnathostomiasis patients showed a positive result for the 29-kDa antigenic band
      of A. cantonensis. The specificity of the 21 and 24-kDa antigenic bands for
      gnathostomiasis and the 29-kDa antigenic band for A. cantonensis was 95.5% and
      100%, respectively. The antigenic bands for the diagnosis of gnathostomiasis and
      angiostrongyliasis in EOM were highly specific.

PMID- 21894379
TI  - Analysis of the expression of toll-like receptors 2 and 4 and cytokine production
      during experimental Leishmania chagasi infection.
AB  - Toll-like receptors (TLRs) recognise pathogen-derived molecules and influence
      immunity to control parasite infections. This study aimed to evaluate the mRNA
      expression of TLRs 2 and 4, the expression and production of the cytokines
      interleukin (IL)-12, interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha,
      IL-17, IL-10 and transforming growth factor (TGF)-beta and the production of
      nitric oxide (NO) in the spleen of mice infected with Leishmania chagasi. It also
      aimed to evaluate any correlations between mRNA expression TLR2 and 4 and
      cytokines and NO production. Infection resulted in increased TLR2-4, IL-17, TNF
      alpha and TGF-beta mRNA expression during early infection, with decreased
      expression during late infection correlating with parasite load. IFN-gamma and IL
      12 mRNA expression decreased at the peak of parasitism. IL-10 mRNA expression
      increased throughout the entire time period analysed. Although TGF-beta, TNF
      alpha and IL-17 were highly produced during the initial phase of infection, IFN
      gamma and IL-12 exhibited high production during the final phase of infection. IL
      10 and NO showed increased production throughout the evaluated time period. In
      the acute phase of infection, there was a positive correlation between TLR2-4,
      TNF-alpha, IL-17, NO, IL-10 and TGF-beta expression and parasite load. During the
      chronic phase of infection, there was a positive correlation between TLR2-4, TNF
      alpha, IL-17 and TGF-beta expression and parasite load. Our data suggest that
      infection by L. chagasi resulted in modulation of TLRs 2 and 4 and cytokines.

PMID- 21894380
TI  - The outcome of acute schistosomiasis infection in adult mice with postnatal
      exposure to maternal malnutrition.
AB  - Maternal malnutrition during the lactation period in early development may have
      long-term programming effects on adult offspring. We evaluated the combined
      effects of parasitological behaviour and histopathological features and
      malnutrition during lactation. Lactating mice and their pups were divided into a
      control group (fed a normal diet of 23% protein), a protein-restricted group (PR)
      (fed a diet containing 8% protein) and a caloric-restricted group (CR) (fed
      according to the PR group intake). At the age of 60 days, the offspring were
      infected with Schistosoma mansoni cercariae and killed at nine weeks post
      infection. Food intake, body and liver masses, leptinaemia, corticosteronaemia,
      collagen morphometry and neogenesis and the cellular composition of liver
      granulomas were studied. PR offspring showed reduced weight gain and hypophagia,
      whereas CR offspring became overweight and developed hyperphagia. The pre-patent
      period was longer (45 days) in both programmed offspring as compared to controls
      (40 days). The PR-infected group had higher faecal and intestinal egg output and
      increased liver damage. The CR-infected group showed a lower number of liver
      granulomas, increased collagen neogenesis and a higher frequency of binucleate
      hepatocytes, suggesting a better modulation of the inflammatory response and
      increased liver regeneration. Taken together, our findings suggest that neonatal
      malnutrition of offspring during lactation affects the outcome of schistosomiasis
      in mice.

PMID- 21894381
TI  - Dengue-2 and yellow fever 17DD viruses infect human dendritic cells, resulting in
      an induction of activation markers, cytokines and chemokines and secretion of
      different TNF-alpha and IFN-alpha profiles.
AB  - Flaviviruses cause severe acute febrile and haemorrhagic infections, including
      dengue and yellow fever and the pathogenesis of these infections is caused by an
      exacerbated immune response. Dendritic cells (DCs) are targets for dengue virus
      (DENV) and yellow fever virus (YF) replication and are the first cell population
      to interact with these viruses during a natural infection, which leads to an
      induction of protective immunity in humans. We studied the infectivity of DENV2
      (strain 16681), a YF vaccine (YF17DD) and a chimeric YF17D/DENV2 vaccine in
      monocyte-derived DCs in vitro with regard to cell maturation, activation and
      cytokine production. Higher viral antigen positive cell frequencies were observed
      for DENV2 when compared with both vaccine viruses. Flavivirus-infected cultures
      exhibited dendritic cell activation and maturation molecules. CD38 expression on
      DCs was enhanced for both DENV2 and YF17DD, whereas OX40L expression was
      decreased as compared to mock-stimulated cells, suggesting that a T helper 1
      profile is favoured. Tumor necrosis factor (TNF)-alpha production in cell
      cultures was significantly higher in DENV2-infected cultures than in cultures
      infected with YF17DD or YF17D/DENV. In contrast, the vaccines induced higher IFN
      alpha levels than DENV2. The differential cytokine production indicates that
      DENV2 results in TNF induction, which discriminates it from vaccine viruses that
      preferentially stimulate interferon expression. These differential response
      profiles may influence the pathogenic infection outcome.

PMID- 21894382
TI  - Comparison of the efficacy of long-lasting insecticidal nets PermaNet(r) 2.0 and
      Olyset(r) against Anopheles albimanus under laboratory conditions.
AB  - Insecticide-treated nets provide a reduction in human-vector contact through
      physical barrier, mortality and/or repellent effects that protect both users and
      non-users, thereby protecting the wider community from vector-borne diseases like
      malaria. Long-lasting insecticide-treated nets (LLINs) are the best alternative.
      This study evaluated the bioefficacy of LLINs PermaNet(r) 2.0 and Olyset(r) under
      laboratory conditions with Anopheles albimanus. The laboratory strain was
      evaluated for insecticide susceptibility with selected insecticides used for
      malarial control. Regeneration time and wash resistance were evaluated with the
      standard bioassay cone technique following WHO guidelines. Heat assistance was
      used for Olyset(r) nets; the nets were exposed to four different temperatures to
      speed the regeneration process. The regeneration study of PermaNet(r) 2.0 showed
      that efficacy was fully recovered by 24 h after one and three washes and wash
      resistance persisted for 15 washes. Regeneration of Olyset(r) nets was not
      observed for nets washed three times, even with the different temperature
      exposures for up to seven days. Thus, for Olyset(r) the wash resistance
      evaluation could not proceed. Differences in response between the two LLINs may
      be associated with differences in manufacturing procedures and species response
      to the evaluated LLINs. PermaNet(r) 2.0 showed higher and continuous efficacy
      against An. albimanus.

PMID- 21894383
TI  - Sequence analysis of the 2009 pandemic influenza A H1N1 virus haemagglutinin gene
      from 2009-2010 Brazilian clinical samples.
AB  - In this paper, we analysed the haemagglutinin (HA) gene identified by polymerase
      chain reaction from 90 influenza A H1N1 virus strains that circulated in Brazil
      from April 2009-June 2010. A World Health Organization sequencing protocol
      allowed us to identify amino acid mutations in the HA protein at positions S220T
      (71%), D239G/N/S (20%), Y247H (4.5%), E252K (3.3%), M274V (2.2%), Q310H (26.7%)
      and E391K (12%). A fatal outcome was associated with the D239G mutation (p <
      0.0001). Brazilian HA genetic diversity, in comparison to a reference strain from
      California, highlights the role of influenza virus surveillance for study of
      viral evolution, in addition to monitoring the spread of the virus worldwide.

PMID- 21894384
TI  - Lower production of IL-17A and increased susceptibility to Mycobacterium bovis in
      mice coinfected with Strongyloides venezuelensis.
AB  - The presence of intestinal helminths can down-regulate the immune response
      required to control mycobacterial infection. BALB/c mice infected with
      Mycobacterium bovis following an infection with the intestinal helminth
      Strongyloides venezuelensis showed reduced interleukin-17A production by lung
      cells and increased bacterial burden. Also, small granulomas and a high
      accumulation of cells expressing the inhibitory molecule CTLA-4 were observed in
      the lung. These data suggest that intestinal helminth infection could have a
      detrimental effect on the control of tuberculosis (TB) and render coinfected
      individuals more susceptible to the development of TB.

PMID- 21894385
TI  - Evaluation of rapid techniques for the detection of mycobacteria in sputum with
      scanty bacilli or clinically evident, smear negative cases of pulmonary and extra
      pulmonary tuberculosis.
AB  - The objective of the current study was to compare two rapid methods, the BBL
      Mycobacteria Growth Indicator Tube (MGIT TM) and Biotec FASTPlaque TB TM (FPTB)
      assays, with the conventional Lowenstein-Jensen (LJ) media assay to diagnose
      mycobacterial infections from paucibacillary clinical specimens. For evaluation
      of the clinical utility of the BBL MGIT TM and FPTB assays, respiratory tract
      specimens (n = 208), with scanty bacilli or clinically evident, smear negative
      cases and non-respiratory tract specimens (n = 119) were analyzed and the
      performance of each assay was compared with LJ media. MGIT and FPTB demonstrated
      a greater sensitivity (95.92% and 87.68%), specificity (94.59% and 98.78%),
      positive predictive value (94.91% and 99.16%) and negative predictive value
      (96.56% and 90.92%), respectively, compared to LJ culture for both respiratory
      tract and non-respiratory tract specimens. However, the FPTB assay was unable to
      detect nontuberculous mycobacteria and few Mycobacterium tuberculosis complex
      cases from paucibacillary clinical specimens. It is likely that the analytical
      sensitivity of FPTB is moderately low and may not be useful for the direct
      detection of tuberculosis in paucibacillary specimens. The current study
      concluded that MGIT was a dependable, highly efficient system for recovery of M.
      tuberculosis complexes and nontuberculous mycobacteria from both respiratory and
      non-respiratory tract specimens in combination with LJ media.

PMID- 21894386
TI  - Ocular toxoplasmosis: evaluation of lacrimal-specific secretory IgA levels in
      both patients with active and inactive phases of the disease.
AB  - Ocular toxoplasmosis can result in recurrent uveitis. Studies have shown that a
      correlation between active ocular toxoplasmosis and the presence of anti
      Toxoplasma gondii secretory IgA (SIgA) in tears. This study compares anti-T.
      gondii SIgA levels in patients' tears during the acute and inactive phases of
      toxoplasmic uveitis. Twenty-nine positive tear specific SIgA for T. gondii
      patients with acute toxoplasmic uveitis were selected and were followed-up for at
      least two years, when the anti-T. gondii SIgA tears levels were determined.
      Specific SIgA for T. gondii was negative in 22 patients (75.86%) and positive in
      seven patients (24.13%) of whom six (85.7%) were followed over three years.
      Average SIgA levels during the acute phase are 1.54 and decrease significantly to
      0.72 (p = 0.0001) during the inactive phase of disease. Because anti-T. gondii
      SIgA in the tear is negative in 75.86% of patients after the acute phase of
      infection, T. gondii SIgA levels may be used as a complementary diagnostic marker
      for active ocular toxoplasmosis.

PMID- 21894387
TI  - Genotyping of two Neisseria gonorrhoeae fluroquinolone-resistant strains in the
      Brazilian Amazon Region.
AB  - We report two ciprofloxacin and ofloxacin-resistant Neisseria gonorrhoeae strains
      that were isolated from the urethral discharge of male patients at the sexually
      transmitted diseases outpatient clinic of the Alfredo da Matta Foundation
      (Manaus, state of Amazonas, Brazil). The gonococci displayed minimal inhibitory
      concentrations (> 32.00 ug/mL) and three mutations in the quinolone resistance
      determining region (S91F and D95G in GyrA and S87R in ParC). Both isolates were
      genotyped using N. gonorrhoeae multi-antigen sequence typing and the analysis
      showed that the ST225 which represented an emerging widespread multi-resistant
      clone that has also been associated with reduced susceptibility to ceftriaxone.
      We recommend continued surveillance of this pathogen to assess the efficacy of
      anti-gonococcal antibiotics in Brazil.

PMID- 21894388
TI  - Prevalence of hepatitis B and C virus infection among leprosy patients in a
      leprosy-endemic region of central Brazil.
AB  - Leprosy and hepatitis B virus (HBV) are highly endemic in some regions of the
      state of Mato Grosso, in central Brazil. The association of leprosy with HBV and
      hepatitis C virus (HCV) was assessed using a seroprevalence study and 191 leprosy
      outpatients were included. Demographic data and the clinical classification of
      leprosy were recorded. Evidence of previous HBV infection was present in 53
      patients (27.7%, 95% confidence interval: 21.9-34.5) and two (1%) were HBsAg
      positive. Five (2.6%) had antibodies to HCV. The prevalence of previous exposure
      to HBV was higher than expected for an adult population in central Brazil. In
      contrast, the prevalence of anti-HCV antibodies was not much higher regarding the
      age range of participants. HBV markers were associated with a higher number of
      sex partners and the use of injections without proper sterilisation of the
      syringes. The number of HBV carriers was small, suggesting that there was no
      increased likelihood of chronification among these patients.

PMID- 21894389
TI  - Hourly activity of Lutzomyia neivai in the endemic zone of cutaneous
      leishmaniasis in Tucuman, Argentina: preliminary results.
AB  - In the present work, the hourly activity of Lutzomyia neivai was studied in the
      southern part of the province of Tucuman, Argentina, in an area of transmission
      of cutaneous leishmaniasis during two months of higher activity. In addition, the
      variables that influenced the abundance of Lu. neivai were evaluated. A total of
      1,146 individuals belonging to Lu. neivai (97%) and Lutzomyia migonei (3%) were
      captured. The hourly activity of Lu. neivai was mainly nocturnal, with a bimodal
      pattern in both months. In January, the variable that most influenced the
      abundance of Lu. neivai was the temperature, whereas in April, that variable was
      humidity. These results may contribute to the design of anti-vectorial control
      measures at a micro-focal scale.

PMID- 21894390
TI  - Can studies where subjects have different follow-up times be analysed through
      binomial regression?

PMID- 21894391
TI  - Case 4/2011 - 49-year-old man with pulmonary valve stenosis and atrial septal
      defect as residual lesions after correction of tetralogy of Fallot, which
      occurred 30 years ago.

PMID- 21894392
TI  - Undergraduate research, medical residency and clinical investigation.

PMID- 21894393
TI  - Noncompaction cardiomyopathy: a current view.
AB  - Isolated non-compaction cardiomyopathy is a rare disease that is likely to
      develop in the embryonic period. It is caused by the intrauterine arrest of the
      myocardial compaction process in the beginning of the fetal development. It is
      characterized by prominent myocardial trabeculations and deep intertrabecular
      recesses, as well as the thickening of the myocardium into two distinct layers
      (compacted and not compacted). Even though this disease is said to be prevalent
      in the pediatric population or together with congenital heart disease, one can
      understand that this disease occurs in isolation, because the diagnosis is
      becoming more common in adult patients that have no other heart disease. The
      clinical manifestations vary greatly, because they range from absence of symptoms
      to congestive heart failure, arrhythmias and systemic thromboembolism.
      Echocardiography is the most widely used diagnostic procedure, but the little
      knowledge about this disease, its similarity to other myocardial diseases and the
      limitation of the echocardiographic technique used delay the diagnosis. The
      purpose of this review is to show that that other imaging techniques, such as
      MRI, CT and left ventriculography have emerged as diagnostic alternatives.

PMID- 21894394
TI  - Stent implantation in surgical cavopulmonary conduit: report of two cases.
AB  - Despite advances in Fontan surgery, obstruction in extracardiac ducts may occur
      and cause clinical deterioration. We report two cases of stent implantation for
      correction of stenosis in the Fontan surgery. Ascites was a common clinical sign;
      a patient was protein losing enteropathy. All procedures were angiographically
      and clinically successful.

PMID- 21894395
TI  - Occlusive venopathy phenotype in hereditary pulmonary arterial hypertension.
AB  - A 33-year-old male with severe hereditary pulmonary arterial hypertension had a
      confirmed diagnosis of occlusive venopathy and microvasculopathy. He remained
      stable for three and a half years on oral sildenafil, 75 mg t.i.d. (six-minute
      walked distance of 375 m vs 105 m at baseline), but required addition of bosentan
      (125 mg b.i.d.), subsequently. Despite the fatal outcome at five years post
      diagnosis, the observations suggest a potential usefulness of vasodilators as a
      bridge for lung transplant in selected cases with significant venous/capillary
      involvement. The occurrence of veno-occlusive and capillary lesions in the
      familial form of pulmonary arterial hypertension reinforces the difficulties with
      the current classification of the disease.

PMID- 21894396
TI  - One decade of stem cell therapy for bone marrow: what is missing?

PMID- 21894397
TI  - Is endovascular treatment of penetrating aortic ulcer the solution?

PMID- 21894398
TI  - Comments on paper by Thomas et al: how to evaluate "quality of publication".

PMID- 21894399
TI  - Additional comments on the paper by Thomas et al: how to evaluate "quality of
      publication".

PMID- 21894402
TI  - The Einstein's frog.

PMID- 21894403
TI  - The importance of the internet for medical societies.

PMID- 21894404
TI  - Fractal dimension in quantifying the degree of myocardial cellular rejection
      after cardiac transplantation.
AB  - INTRODUCTION: The term "Fractal" is derived from the Latin fractus meaning
      "irregular" or "broken" considering the observed structure with a non-integer
      dimension. There are many studies which employed the Fractal Dimension (FD) as a
      diagnostic tool. One of the most common methods for its study is the "Box
      Counting Method". OBJECTIVE: The aim of the present study was to try to establish
      the contribution of FD in the quantification of myocardial cellular rejection
      after cardiac transplantation. METHODS: Microscopic digital images were captured
      at 800x600 resolution (magnification 100x). FD was calculated with the aid of
      "ImageJ software" with adaptations. The classification of the degrees of
      rejection was in agreement with the "International Society for Heart and Lung
      Transplantation" (ISHLT 2004). The final report of the degree of rejection was
      confirmed and redefined after an exhaustive review of the slides by an external
      experienced pathologist. 658 slides were evaluated with the following
      distribution among the degrees of rejection (R): 335 (0R); 214 (1R); 70 (2R); 39
      (3R). The data were statistically analyzed with Kruskal-Wallis tests and ROC
      curves being considered significant values of P < 0.05. RESULTS: There was
      significant statistical difference between the various degrees of rejection with
      the exception of R3 versus R2. The same trend was observed in applying the ROC
      curve. CONCLUSION: FD may contribute to the assessment of myocardial cellular
      rejection. Higher values are directly associated with progressively higher
      degrees of rejection. This may help in decision making of doubtful cases and
      those which contemplate the intensification of immunosuppressive medication.

PMID- 21894405
TI  - A bovine pericardium rigid prosthesis for left ventricle restoration: 12 years of
      follow-up.
AB  - BACKGROUND: Myocardial infarction might result in dilated left ventricle and
      numerous techniques have been described to restore the original left ventricle
      shape and identify tools for late survival assessment. The aim of this study is
      to compare our experience with a modified Dor procedure using a rigid prosthesis
      to the septal anterior ventricular exclusion procedure (SAVE) for left ventricle
      restoration. The EuroScore index for prediction of late follow up survival was
      evaluated. METHODS: We evaluated 80 patients who underwent left ventricle
      restoration between 1999 to 2007 and eight patients were excluded with incomplete
      data. A modified Dor procedure with rigid prosthesis (MD group) was performed on
      53 patients and 19 underwent the septal anterior ventricular exclusion procedure
      (SAVE group). The patients were classified according their left ventricle shape
      as type I, II or III. Kaplan-Meier and Cox proportional hazard ratio regressions
      analysis were performed to assess survival after both techniques and expected
      surgical mortality using EuroScore index ranking after 12 years of follow up.
      RESULTS: The operative mortality was comparable in both groups ranked by
      EuroScore index. The groups were comparable for all clinical data, except the MD
      group had more patients using intra-aortic balloon pumps before surgery, (5.7%
      vs. 0; P<0.01). Kaplan Meier analysis by left ventricle shape showed comparable
      survival for all patients, with slightly higher survival for type I. Kaplan Meier
      analysis of all death showed equivalent survival curves for both techniques after
      12 years of follow up (71.5 +/- 12.3 vs. 46.6 +/- 20.5 years; P=0.08). Kaplan
      Meier analysis of EuroScore index for all patients showed a difference between
      the three ranked categories, i.e., 0 to 10%, 11 to 49% and higher than 50%
      expected surgical mortality after 12 years of follow up (70.9 +/- 16.2 vs. 67.5
      +/- 12.7 vs. 53.0 +/- 15.5; P=0.003). CONCLUSION: The MD procedure showed
      consistent ejection fraction improvements after long term follow up. Survival was
      comparable for all ventricular types and for the MD and SAVE procedures. The
      EuroScore index is a useful index for late survival assessment of ventricular
      restoration techniques.

PMID- 21894406
TI  - Osteopontin expression and its possible functions in the aortic disorders and
      coronary artery disease.
AB  - BACKGROUND: Osteopontin (OPN) has been verified to be closely associated with
      oncogenesis and remodeling processes. But this cytokine was rarely assessed in
      the presence of aortopathies, especially acute aortic dissection. The aim of the
      present study was to evaluate the expressions of OPN by way of molecular
      biological approaches so as to offer a better understanding of the possible
      mechanisms of the aortopathies. METHODS: Consecutive patients with type A acute
      aortic dissection (20 patients), aortic aneurysm (nine patients) or coronary
      artery disease (21 patients) referred to this hospital for surgical operations
      were enrolled into this study. Blood samples of the surgical patients after
      systematic heparinization, and control fast morning blood samples drawn from 21
      young healthy volunteers who had no evidence of any healthy problems were
      investigated for enzyme linked immunosorbent assay (ELISA). The surgical
      specimens of the aortic tissues collected from the surgical patients during the
      operations were obtained for quantitative realtime reverse transcription
      polymerase chain reaction (RT-PCR) for OPN mRNA, western blot assay for OPN
      protein, and for immunohistochemical staining of OPN. Ascending aortic tissues
      from the autopsies of the healthy individuals dying of accident were obtained as
      controls of immunohistochemistry. RESULTS: By quantitative RT-PCR, the
      expressions of OPN mRNA were all upregulated in all three surgical groups. The
      quantitative results did not reveal any intergroup differences. Western blot
      assay revealed that OPN was positive with similar intensities of expressions in
      all three surgical groups. Quantitative western blot analyses of OPN expressions
      did not show any significance between groups. The OPN expressions by ELISA in the
      aortic tissue were 3.09311 +/- 1.65737, 3.40414 +/- 1.15095, and 1.68243 +/-
      0.31119 pg/mg protein in the aortic dissection, aortic aneurysm, and coronary
      artery disease groups, respectively. The OPN level of the patients with coronary
      artery disease was much lower than those with aortic dissection (P = 0.033) or
      with aortic aneurysm (P = 0.019). By unparametric tests, there were significant
      differences in the aortic OPN contents among aortic dissection, aortic aneurysm
      and coronary artery disease groups (P < 0.01). A significant direct correlation
      was present between plasma OPN concentration and the time interval from the onset
      to surgery of aortic dissection (Y = 0.1420X + 2.4838, r2 = 0.5623, r = 0.750, P
      = 0.032). By immunohistochemistry, OPN was expressed in the aortic cells: in the
      intima, it was weaker in all three surgical groups in comparison with the healthy
      control; in the media, it was weak in the aortic dissection, intense positive in
      aortic aneurysm, focal positive in the coronary artery disease, but evenly
      positive in the healthy control groups; and in the adventitia, it was positive in
      the aortic dissection, coronary artery disease and healthy control groups, but
      weak positive in the aortic aneurysm group. CONCLUSION: These data may provide
      evidences that OPN may play a role in the pathogenesis of aortopathies including
      aortic dissection, aortic aneurysm, and coronary artery disease. OPN might be of
      potential perspective as a clinically diagnostic tool in the evaluations of the
      complex remodeling process incorporating vascular injury and repair.

PMID- 21894407
TI  - Skeletonized left internal thoracic artery is associated with lower rates of
      mediastinitis in diabetic patients.
AB  - BACKGROUND: Mediastinitis is a serious complication of median sternotomy and is
      associated to significant morbidity and mortality. Diabetes is a feared risk
      factor for mediastinitis and viewed with caution by cardiovascular surgeons.
      OBJECTIVE: To identify risk factors for mediastinitis in diabetics undergoing
      CABG surgery with use of unilateral ITA in the Division of Cardiovascular Surgery
      of Pronto Socorro Cardiologico de Pernambuco - PROCAPE. METHODS: Retrospective
      study of 157 diabetics operated between May 2007 and April 2010. Nine
      preoperative variables, five intraoperative variables and seven postoperative
      variables possibly involved in the development of postoperative mediastinitis
      were evaluated. Univariate and multivariate logistic regression analyses were
      applied. RESULTS: The incidence of mediastinitis was 7% (n=11), with a lethality
      rate of 36.1% (n=4). Variables associated with increased risk of mediastinitis
      were: use of pedicled ITA (OR 8.25, 95% CI 2.03 to 66.10, P=0.016), postoperative
      renal complications (OR 5.10, 95% CI 1.03 to 25.62, P=0.049) and re-operation (OR
      7.45, 95% CI 1.24 to 42.17, P=0.023). In multivariate analysis using backward
      logistic regression, only one variable remained as independent risk factor: use
      of pedicled ITA (OR 7.64, 95% CI 1.95 to 61.6, P=0.048), in comparison to
      skeletonized ITA. CONCLUSIONS: We suggest that diabetics should be considered for
      strategies to minimize risk of infection. In diabetics that undergo unilateral
      ITA, the problem seems to be related to how ITA is harvested. Diabetics should
      always be considered for use of skeletonized ITA.

PMID- 21894408
TI  - Predictors of infection in post-coronary artery bypass graft surgery.
AB  - BACKGROUND: Although coronary artery bypass grafting (CABG) is a good alternative
      therapy in severe arterial disease, it may evolve with complications, especially
      infections. OBJECTIVES: To determine the incidence of infection in post-CABG and
      its clinical predictors in a cardiology reference center in Brazil. METHODS:
      Cohort study. Data were collected from all patients undergoing CABG between
      January/2004 and February/2006, excluding emergency surgery, absent record of
      glucose blood levels preoperatively and infection prior to surgery. STATISTICAL
      ANALYSIS: Student's t test, chi square, logistic regression. RESULTS: We
      evaluated 717 patients, 61.9 +/- 11 years old, 67.1% were men, 29.6% with
      diabetes, of whom 137 (19.1%) developed infection (62% respiratory, 25%
      superficial wound, 9.5% urinary, 3.6% deep wound). Diabetes was more prevalent in
      those who developed infection, as well as prolonged time of indwelling central
      venous catheter (79.3 +/- 40.5 vs. 61.0 +/- 19.3 hours, P<0.001). After
      multivariate analysis (model adjusted for dyslipidemia, hypertension, smoking and
      leukocytes), both diabetes (OR 4.18 [2.60-6.74]), prolonged central venous line
      (OR 1.019 [1.00-1.02] and cardiac catheterism (OR 2.03 [1.14-3.60] remained
      predictors of infection. While diabetes is associated with a higher percentage of
      infections (P <0.001), preoperative serum glucose was not associated with
      increased risk of infection. CONCLUSIONS: Diabetes and permanence of central
      venous catheters were associated with development of infection in post-CABG. The
      preoperative blood glucose was not a predictor of risk of infection. It is
      probably necessary to study with greater detail glycemic control trans- and post
      operatively.

PMID- 21894409
TI  - Design conception and experimental setup for in vitro evaluation of mitral
      prosthetic valves.
AB  - BACKGROUND: Since most complications related to the operation of prosthetic heart
      valves is due to disturbances of flow, its hydrodynamic characterization is a
      useful aid in the design of new prostheses. Simulations of pulsatile flow in
      cardiac prostheses began nearly 40 years ago, through the development of
      different mock human circulatory systems, improving the clinical results
      interpretation. A new design of a pulse duplicator system was developed at
      Polytechnic School of USP to study prosthetic heart valves. OBJECTIVE: To present
      the conception of a new mock circulatory system for hydrodynamic simulations of
      cardiac prosthetic valves and the assembly plan of an experiment whose focus is
      the test of mitral prosthesis. METHODS: Its conception is based on the state-of
      art's review of these studies and the experience got with the previous mock
      circulatory systems, particularly the one used in the Instituto Dante Pazzanese
      de Cardiologia, Sao Paulo, SP, Brazil. RESULTS: In this design, an electric
      servomotor controlled by computer emits, through a hydraulic piston, a pulse to
      the left ventricular chamber model, where the heart valves are accomodated. To
      characterize, in the future, the dynamic operation of mitral prosthetic valves,
      an experimental setup was mounted to provide measurements of volumetric flow,
      instantaneous pressure and velocity fields on these valves. Optical access is
      conveniently provided on the design, making possible the use, in the future, of a
      LDA system. CONCLUSIONS: In order to improve the analysis of hydrodynamic shear
      stress and prediction of haemolysis, the experimental results may be used to
      regulate a numerical model using 'Computational Fluid Dynamics' (CFD).

PMID- 21894410
TI  - Brazilian perfusionists and arterial roller pump adjustment: comparison between
      static and dynamic calibration method.
AB  - INTRODUCTION: Roller pumps play an important role in extracorporeal circulation.
      However, occlusion of the rollers should be adequately performed and this can be
      adjusted mainly by two methods: static and dynamic. OBJECTIVE: To investigate how
      the Brazilian perfusionists adjust arterial roller pumps in their services and
      evaluate the application of a Device to Assist Calibration (DAC) that facilitates
      roller adjustment by the dynamic calibration method. METHODS: We installed a
      roller pump with accessories to perform adjustment by drop rate (static
      calibration) and dynamic calibration methods during the XXVIII Brazilian Congress
      of Extracorporeal Circulation. Perfusionists were asked to adjust the roller pump
      according to the procedure they usually do in their service. After each
      adjustment pressure was measured by dynamic calibration method with DAC. The
      research was approved by the Research Ethics Committee of UNICAMP, No 1144/2010.
      RESULTS: There were 56 perfusionists in this study. Pressure average of 56
      measurements of dynamic calibration was 434 +/- 214 mmHg; 76% of measurements
      were within the recommended range for the use of the dynamic calibration method
      (between 150 and 500 mmHg). CONCLUSION: Brazilian perfusionists tend to adjust
      roller pumps with less occlusive settings. The amplitudes of the dynamic
      calibration pressure tend to be smaller for more experienced perfusionists
      because their skills increase with time. The device can be used by the
      perfusionist to adjust roller pumps with greater accuracy and mainly
      repeatability in few minutes.

PMID- 21894411
TI  - Effects of the use of mechanical ventilation weaning protocol in the Coronary
      Care Unit: randomized study.
AB  - OBJECTIVE: To compare mechanical ventilation weaning based on a protocol using
      the spontaneous breathing trial against mechanical ventilation weaning without a
      standardized protocol in heart patients. METHODS: Prospective, open, randomized
      study. In 2006, 36 patients undergoing mechanical ventilation for over 24 hours
      were randomized into two groups: control group - eighteen patients whose
      mechanical ventilation weaning was performed according to the different
      procedures adopted by the multidisciplinary team; and experimental group -
      eighteen patients weaned according to previously established protocol. RESULTS:
      Control group patients started the weaning process sooner than experimental group
      patients (74.7 +/- 14.7 hours vs. 185.7 +/- 22.9 hours, P=0.0004). However, after
      the experimental group patients were ready for weaning, the extubation was
      carried out more rapidly than in the control group (149.1 +/- 3.6 min vs. 4179.1
      +/- 927.8 min, P < 0.0001) with significantly lower reintubation rates (16.7% vs.
      66.7%, P = 0.005). CONCLUSION: The use of a specific protocol based on the
      spontaneous breathing trial for mechanical ventilation weaning in heart patients
      had better outcomes than weaning carried out without a standardized protocol,
      with shorter weaning times and lower reintubation rates.

PMID- 21894413
TI  - Right coronary artery anatomy: anatomical and morphometric analysis.
AB  - BACKGROUND: It is necessary knowing the large variability of right coronary (RCA)
      artery specialty for its implications in surgical procedures and clinic events.
      This variability is usually related to the length, branches quantity, origin and
      irrigated territories. OBJECTIVE: To evaluate by direct examination the
      morphologic expression of RCA in Colombian people. METHODS: RCA were measured in
      221 fresh hearts by RCA ostium canalization with polyester synthetic resin that
      was injected in their branches. RESULTS: The caliber of the RCA proximal segment
      and at the level of the acute angle of the heart was 3.42 +/- 0.66 mm and 2.9 +/-
      0.50 mm, respectively. It ended between crux cordis and the left margin in 75.6%
      of specimens. Posterior interventricular artery (PIA) reached the inferior third,
      or the apex, or the anterior interventricular sulcus in 149 (67.4%) cases.
      Sinoatrial node artery (SNA) originated in the right coronary in 134 (60.6%)
      cases, 77 (34.9%) from circumflex artery (CxA) and from both in 10 (4.5%).
      Posterior right diagonal artery (PRDA) was noted in 38 (17.2%) hearts, but only
      6% of the sample with long PIA, concomitantly presented the PRDA (P = 0.001). In
      right dominance SNA were originated from RCA in 54.7% and form CxA in 46.3% (P =
      0.06). CONCLUSIONS: Caliber of the RCA and its branches is lesser than the
      majority of previous studies, while the PRDA frequency is slightly higher than
      the reported in literature. Clinical and pathological scenarios by these
      variations should be taken into account: hemodynamic procedures, cardiac surgery
      and arrhythmias from coronary occlusive disease.

PMID- 21894412
TI  - The impact of blood transfusion on morbidity and mortality after cardiac surgery.
AB  - OBJECTIVES: To analyze the impact of blood transfusion on the incidence of
      clinical outcomes postoperatively (PO) from cardiac surgery. METHODS:
      Retrospective cohort study. We analyzed 4028 patients undergoing coronary artery
      bypass grafting (CABG), valve (TV), or both, in Brazilian tertiary university
      hospital between 1996 and 2009. We compared the postoperative complications
      between patients with blood transfusion (n = 916) and non-blood transfusion (n =
      3112). Univariate analysis was performed using the Student t test, and
      multivariate logistic regression bivariate (stepwise forward). Were considered
      significant variables with P <0.05. RESULTS: Patients who received blood
      transfusions had more infectious episodes as mediastinitis (4.9% vs. 2.2%, P
      <0.001), respiratory infection (27.8% vs 17.1%, P <0.001) and sepsis (6.2% vs.
      2.5%, P <0.001). There were more episodes of atrial fibrillation (AF) (27% vs.
      20.4%, P <0.001), acute renal failure (ARF) (14.5% vs 7.3%, P <0.001) and stroke
      (4.8% vs. 2.6%, P = 0.001). The length of PO hospital stay was higher in
      transfused (13 +/- 12.07 days vs. 9.72 +/- 7.66 days, P <0.001). However,
      mortality didn't differ between groups (10.9% vs. 9.1%, P = 0.112). The
      transfusion was shown to be a risk factor for: respiratory infection (OR: 1.91,
      95% CI 1.59-2.29, P <0.001), AF (OR: 1.35, 95% CI 1.13-1.61, P = 0.01), sepsis
      (OR: 2.08, 95% CI 1.4-3.07, P <0.001), mediastinitis (OR: 2.14, 95% CI: 1.43
      3.21, P <0.001), stroke (OR: 1.63, 95% CI 1.1-2.41, P = 0.014) and ARF (OR 1.8,
      95% CI: 1.39-2.33, P <0.001). CONCLUSION: The blood transfusion is associated
      with increased risk of infectious events, episodes of AF, ARF and stroke, as well
      as the increased length of hospital stay but not mortality.

PMID- 21894414
TI  - Quality of life of patients with implantable cardioverser-defibrillator: the
      usage of SF-36 questionnaire.
AB  - OBJECTIVE: To observe the quality of life of patients with implantable
      cardioverser-defibrillator (ICD). METHODS: Descriptive research with quantitative
      approach by means of an interview and the analysis of the Questionnaire SF-36 in
      a cardiovascular outpatient service. Fifty patients users of this device
      participated in this study during their medical follow-up in the period from
      January to December. RESULTS: Out of the subjects, 19 (38%) were female and 31
      (62%) male. The average age was 58.4 years, ranging from 21 to 75 years. Two
      domains regarding limitations by physical and emotional aspects below score 50
      were observed The social aspects domain presented the higher score; 80,5. Most of
      the users reported that their health is a little better compared with a year ago.
      CONCLUSION: The results showed that individuals' quality of life is impaired,
      with lower scores for physical and emotional aspects. There was not a correlation
      between quality of life and age, gender, marital status and educational level.
      However, they feel comfortable and safe with ICD benefits since it provides their
      maintenance in being alive protecting them of sudden death.

PMID- 21894415
TI  - Physical therapy in postoperative cardiac surgery: patient's perception.
AB  - INTRODUCTION: Many strategies to improve services provided by for physiotherapy
      are based on patients satisfaction. Listen and observe the behavior of patients
      in a hospital is crucial to understanding and improvement of service and the
      hospital. OBJECTIVE: This study aimed to identify the patient's perception
      undergoing cardiac surgery on the physiotherapy service provided to wards of
      hospitals for heart surgery reference in the city of Maceio, AL, Brazil, and from
      that information detect what actions are perceived as priorities for which are
      noteworthy plans for improvements in quality of care. METHODS: Cross-sectional
      study, conducted in quality and quantity of reference hospitals in cardiac
      surgery in the city of Maceio, AL, Brazil, in the period from September to
      November 2008. The study included 30 users of the Sistema Unico de Saude, of
      which 12 (40%) female and 18 (60%) males. The average age of this sample was 49.2
      +/- 11.9 years and most belonged to socioeconomic class D (36.7%). RESULTS: It
      was found that only 16.7% had contact with the physiotherapist before surgery.
      Regarding educational guidelines about postoperative period, only 2.9% patients
      reported having received them. However, 56.8% rated the care as good and 100% of
      patients reported believing that physiotherapy could improve their health status.
      CONCLUSION: We suggest the implementation of preoperative physical therapy
      protocols with preventive measures and educational as well as new researchs that
      may characterize the population of users of health plans/private.

PMID- 21894416
TI  - Mortality within the endovascular treatment in Stanford type B aortic
      dissections.
AB  - BACKGROUND: Endovascular stent-graft repair of aortic dissections is a relatively
      new procedure, and although apparently less invasive, the efficacy and safety of
      this technique have not been fully established. OBJECTIVE: To evaluate mortality
      in patients with complicated Stanford type B aortic dissections submitted to
      endovascular treatment. METHODS: Clinical, anatomical, imaging and autopsy data
      of 23 patients with complicated type B aortic dissections were reviewed from
      November 2004 to October 2007. The main indications for transluminal thoracic
      stent-grafting included: persistent pain in spite of medical therapy, signs of
      distal limb ischemia, signs of aortic rupture, progression of aneurismal dilation
      of the descending aorta during follow-up (defined as a diameter > 50 mm) and the
      diameter of descending thoracic aorta of 40 mm or larger at the onset of aortic
      dissection. Data were analyzed statistically; all p-values were two-tailed and
      differences < 0.05 were considered to indicate statistical significance.
      Continuous variables were expressed as mean (+/- SD), and medians were compared
      by the Student's t test. Differences in categorical variables between the groups
      were analyzed by the Chi-square or Fisher's exact test. RESULTS: The procedure
      presented primary technical success in 82.6% of patients. Four patients (17.4%)
      had an incomplete proximal entry seal. Three patients (13%) died within 30 days
      of the procedure and eight patients (34.8%) died after 30 days. CONCLUSION:
      Endovascular correction of complicated Stanford type B aortic dissections is a
      feasible and effective treatment option.

PMID- 21894417
TI  - The impact of carotid artery disease on outcomes of patients undergoing coronary
      artery bypass grafting.
AB  - OBJECTIVE: Although the overall complication rate has been decreased
      significantly in recent years, stroke is a severe complication after coronary
      bypass operations. The purpose of this study is to evaluate the influence of
      carotid artery disease on the results of patients under CABG operation. METHODS:
      In a retrospective cohort study, 1,978 patients under CABG operation were studied
      in Shariati Hospital between April 2002 and March 2006. The patients who had only
      valve replacement or non-CABG procedure were excluded from this study. As part of
      preoperative evaluation, carotid duplex ultrasonography scans were performed. In
      order to estimate the degree of carotid arteries stenosis, ultrasound imaging
      measurement and velocity criteria were considered. The patients were classified
      into three groups: those with no significant stenosis of the internal carotid
      artery (ICA) (moderate) group A, those with significant stenosis (sever) group B
      and those with the occluded ICA (critical) group C. Finally, all data were
      analyzed by SPSS software. Statistical analyses were performed using the
      following testes; chi-square, Fisher exact and Student's t tests. RESULTS: The
      distribution of the 1,978 patients undergoing CABG operation were as follows:
      group A = 1,938, group B = 30, and group C = 10. The results of the evaluations
      show that perioperative stroke rates were 1.2% (24 patients) in group A, 0.4%
      (eight patients) in group B and 0.3% (six patients) in group C (P<0.0001).
      Furthermore, perioperative mortality rates for groups A, B and C were 0.1% (two
      patients), 0.3% (five patients) and 0.4% (seven patients), respectively
      (P<0.0001). CONCLUSION: The stroke and mortality in patients undergoing CABG are
      increased when ICA occlusion is present.

PMID- 21894418
TI  - Pediatric cardiac surgery: what to expect from physiotherapeutic intervention?
AB  - This study aims to gather and present scientific evidence on the role of a
      physiotherapist in the pre, peri and postoperative of pediatric cardiac surgery.
      This professional is able to prevent, minimize or reverse possible respiratory
      dysfunction and motor sequelae resulting from these interventions. Studies
      discuss the involvement of respiratory system, specifically the clearance of
      bronchial secretions and ventilatory adequacy, as a result of surgical procedure.
      Scientific evidences suggest the effectiveness of physiotherapy in reducing
      indices of: pneumonia, atelectasis, hospitalization, sequelae deleterious and
      length of bed restriction, beyond clinical improvement. These data confirm
      positive contribution of physiotherapeutic intervention in these surgeries.

PMID- 21894419
TI  - Cardiac surgery and hypertension: a dangerous association that must be well
      known.
AB  - It is well-known that hypertension is a very common disease, and severe
      cerebrovascular accidents might occur if the blood pressure is not properly
      controlled. However, conditions associated with uncontrolled hypertension may be
      overlooked, and may become critical and eventually require a surgical
      intervention on an urgent basis. Coronary artery disease, acute aortic syndrome,
      congenital and valvular heart disease, and arrhythmias are under this topic of
      discussion. Of them, coronary artery disease including myocardial infarction and
      especially postinfarction myocardial rupture, and aortic dissection are major
      critical situations that physicians may encounter in clinical practice. The role
      that hypertension plays in these conditions can be complex, including
      hemodynamic, electrophysiological and biomolecular factors, where the latter may
      prevail in the current era. Coronary artery disease may be associated with a
      reduced nitric oxide synthesis. Transforming growth factor and matrix
      metalloproteinases have been observed in relation to aortic syndrome. Wnt, p38
      and JNK signaling pathway may be involved in the development of ventricular
      hypertrophy responsible for cardiac arrythmias. Various gene phynotypes may
      present in different congenital heart defects. This article is to present these
      conditions, and to further discuss the possible etiologies and the potential
      treatment strategies so as to highlight the relevance at a prognostic level.

PMID- 21894420
TI  - Comparative experimental study between L-Hydro treated pulmonary homograft and
      fresh pulmonary homograft.
AB  - OBJECTIVE: In an effort to make available homografts preserved in a simpler and
      less costly way, we evaluated the polyethyleneglycol, L-Hydro (LH) method, that
      consists in the controlled extraction of antigenic substances and the
      incorporation of anti-inflammatory and anti-thrombotic agent. METHODS: We
      substituted the pulmonary trunk in ten ovines, seven received LH treated
      pulmonary homografts and three, fresh pulmonary homografts, orthotopically
      implanted and followed-up for 320 days. Ovines where evaluated by means of
      laboratory tests, echocardiographic exams. At the 320 days, were euthanized,
      hemodynamic, radiology, macroscopic, optic/electronic microscopic,
      scanning/transmission evaluations were performed. Results were analyzed by
      Student t test of independent samples for continuous data, by variance analysis
      of repeated measures, and by Fisher exact test for categorical data. RESULTS: We
      couldn't establish relevant differences in clinical evolution and laboratory
      tests between groups. Echocardiogram revealed difference in pulmonary medium
      gradient, which was significant 10 months follow-up, higher in the control group.
      Radiologic and macroscopic evaluations didn't established differences. In the
      optic/electronic microscopic evaluation, liner and interstitial cells were
      equally found in both groups. The cell liner percent calculated in both groups
      was similar. Cellularity nodules were observed only infresh homograft group.
      CONCLUSIONS: These data indicate that both groups presented similar
      clinical/hemodynamic performances. The LH group's echocardiogram presented a
      better performance. It also presented histological evidences of interstitial and
      endothelial cell repopulation. In the macro/optic and electronic microscopic
      analysis, group L-H presented macroscopy/histological structure and ultra
      structural similar to the fresh group, with the exception of nodules with higher
      interstitial cellularity, present only in the fresh homograft group.

PMID- 21894421
TI  - Emergency autologous vein graft reconstruction after using a vascular closure
      device.
AB  - An emergency operation for access related acute critical limb ischemia with signs
      of infection is described. Inguinal femoral reconstruction was performed with a
      bifurcated graft constructed from the ipsilateral saphenous vein.

PMID- 21894422
TI  - Postpartum patient with thrombosis of mechanical prostheses and acquired
      supravalvular aortic stenosis.
AB  - The blood hypercoagulability in pregnancy increases significantly the incidence
      of thrombosis of mechanical valves. Acquired supravalvular aortic stenosis is
      extremely rare. We report the case of an immediate postpartum patient with aortic
      mechanical prostheses and acquired supravalvular aortic stenosis who underwent
      emergency heart surgery, with severe hemodynamic instability, using adapted
      surgical technique for correction of supravalvular stenosis with satisfactory
      clinical and echocardiography results.

PMID- 21894423
TI  - Transfixing gunshot wound to the heart: case report.
AB  - Penetrating cardiac trauma carries high mortality rates. It has been commonly
      associated with stabbing, but increasing urban violence has led to growing
      numbers of gunshot heart wounds. The latter have higher mortality rates among
      penetrating cardiac injuries and may affect multiple heart chambers, with
      mortality rates even higher. We report a patient, victim of an attempted armed
      robbery, who had a transfixing gunshot wound to the heart, successfully operated
      at our institution.

PMID- 21894424
TI  - Immediate postoperative period of cardiac surgery: routine nursing for patient's
      admission to the Intensive Care Unit.

PMID- 21894425
TI  - Prof. Dr. Rubens de Guimaraes Santos: flawless surgeon.

PMID- 21894426
TI  - Write well or perish: courses and services help researchers to write a good
      scientific paper.

PMID- 21894427
TI  - Letter to the editor.

PMID- 21894428
TI  - Crack cocaine craving: behaviors and coping strategies among current and former
      users.
AB  - OBJECTIVE: To understand crack cocaine craving among users and describe craving
      behaviors and coping strategies. METHODOLOGICAL PROCEDURES: Qualitative study
      with a non-random criterion sample consisting of 40 current and former crack
      cocaine users conducted in Sao Paulo, southeast Brazil, in 2007 and 2008.
      Respondents were selected using snowball sampling technique. In-depth semi
      structured interviews were conducted until theoretical saturation was attained.
      All interviews were transcribed and content analysis was performed to construct
      inferences and hypotheses based on the narratives. ANALYSIS OF RESULTS: The
      respondents showed a similar gender distribution, were 18 to 50 years of age, and
      had different levels of education. Most were from low-income background. In
      addition to craving resulting from crack cocaine withdrawal and environmental and
      emotional cue effects, it was found that crack cocaine itself triggers craving.
      The latter appeared to be a strong trigger of binge episodes. Binge episodes made
      them lose their moral values, and act dangerously to get more drug. The most
      common ways reported to get crack cocaine or money to buy it were: prostitution,
      manipulation of other people, go into debt, sell personal belonging to buy drug
      and theft. The respondents reported strategies to overcome their cravings as well
      as pharmacological and behavioral approaches to prevent cravings such as eating,
      having sex, playing soccer, working, avoiding social situations of crack use and
      taking depressants. CONCLUSIONS: Crack cocaine binges are caused by a craving
      induced by the effects of crack cocaine itself. Users develop self-control
      strategies to cope with their cravings that may help improve their drug use and
      treatment effectiveness.

PMID- 21894429
TI  - Preliminary psycometric assessment of the Brazilian version of the DISABKIDS
      Atopic Dermatitis Module.
AB  - OBJECTIVE: To assess preliminary psychometric properties of the Brazilian
      Portuguese version of a questionnaire for measuring health-related quality of
      life in children and adolescents with atopic dermatitis. METHODS: Cross-sectional
      study with a sample consisting of 52 children and adolescents aged 8 to 18
      diagnosed with atopic dermatitis, and their parents or caregivers, selected at
      the dermatology department of a university hospital in the city of Sao Paulo,
      Southeast Brazil, in 2009. Construct validity, internal consistency and agreement
      between the responses of children and adolescents and their parents or caregivers
      were assessed in the Brazilian Portuguese version of the DISABKIDS-Atopic
      Dermatitis Module (ADM). RESULTS: Adequate internal consistency was found with
      Cronbach's alpha coefficients of 0.7024/0.8124 and 0.7239/0.8604. The multitrait
      multimethod analysis for assessing convergent validity showed measures higher
      than 0.30 for all items. The analysis showed good discriminant validity.
      Agreement between child self-report and parent proxy-report was evaluated using
      intra-class correlation with measures impact and social stigma of disease of
      0.8173 and 0.7629, respectively. CONCLUSIONS: The study results showed that the
      DISABKIDS-ADM can be used by Brazilian researchers after its complete validation
      as it showed adequate preliminary psychometric properties and can be considered a
      valid, reliable instrument.

PMID- 21894430
TI  - HDAC inhibitor 4-phenylbutyrate preserves immature phenotype of human embryonic
      midbrain stem cells: implications for the involvement of DNA methyltransferase.
AB  - Cell replacement and gene therapy using neural stem cells (NSCs) have been widely
      touted as a promising treatment for CNS diseases including brain tumors. Histone
      deacetylase (HDAC) inhibitors have been used to explore mechanisms behind the
      lineage-specific differentiation of NSCs and as modulators of gene therapy. We
      have used the human embryonic midbrain stem cell line NGC-407 and the HDAC
      inhibitor 4-phenylbutyrate (4-PB) to investigate the differentiation from
      epigenetic perspectives. NGC-407 cells can differentiate into both neurons and
      glial cells, evidenced by morphological characteristics as well as up-regulation
      of the respective markers beta-tubulin III and glial fibrillary acidic protein
      (GFAP) and simultaneous down-regulation of the NSC-marker nestin. Genomic DNA
      extracted from the differentiating cells was globally more methylated than that
      of the proliferating cells. The differentiating cells showed increased expression
      of the de novo DNA methyltransferase DNMT3B along with strong immunoreactivity in
      the cell nuclei. When these cells were treated with 4-PB, both the astrocytic and
      the neuronal differentiation phenotypes were suppressed, which paralleled a
      substantially weakened DNMT3B immunoreactivity in the cell nuclei. Importantly, 4
      PB treatment preserves the immature phenotype of these differentiating cells as
      indicated by Western blot analysis and immunocytochemical analyses of the NSC
      markers, nestin and CD133. Nestin becomes entirely degraded 5 days after
      induction of differentiation, but upon exposure to 4-PB, some of the
      differentiating cells retain the integrity of nestin and concurrently, CD133 is
      also up-regulated. Taken together, the data suggests that HDAC activity is
      necessary for human embryonic NSC differentiation.

PMID- 21894431
TI  - Levels of acute inflammatory biomarkers in advanced prostate cancer patients with
      alpha2-macroglobulin deficiency.
AB  - C-reactive protein (CRP), serum amyloid A (SAA), interleukin-6 (IL-6), alpha1
      antitrypsin (alpha1AT), alpha1-acid glycoprotein (alpha1AG) and ceruloplasmin
      (CP) are acute inflammatory biomarkers that increase in various conditions
      including infection, inflammation, malignancy and tissue disturbance. In
      contrast, alpha2-macroglobulin (alpha2M) is involved in inflammation through its
      function as a carrier protein of IL-6. We had previously reported on advanced
      prostate cancer (PCa) patients with multiple distant bone metastases in whom
      serum alpha2M levels were markedly decreased (alpha2M deficiency). However, the
      relationship between serum levels of alpha2M and acute inflammatory biomarkers in
      PCa patients with or without alpha2M deficiency has not been demonstrated. In the
      present study, we examined serum levels of CRP, SAA, IL-6, alpha1AT, alpha1AG and
      CP in PCa patients with or without alpha2M deficiency to establish clinical
      significance and changes in these biomarkers during PCa disease progression. We
      found that upon addition of recombinant IL-6 (rIL-6) to serum from PCa patients
      with alpha2M deficiency, since a function of alpha2M is to bind and stabilize IL
      6, the alpha2M-IL-6 complex and free endogenous IL-6 were not detectable. Serum
      levels of the alpha2M-independent markers, alpha1AT, alpha1AG and CP, in all PCa
      patients regardless of alpha2M deficiency were significantly higher than in
      healthy controls, but those of the alpha2M-dependent molecules, CRP, SAA and IL
      6, were not increased in PCa patients with alpha2M deficiency. Therefore,
      quantitation of both alpha2M-dependent (CRP, SAA and IL-6) and alpha2M
      independent (alpha1AT, alpha1AG and CP) acute inflammatory biomarkers in advanced
      PCa patients may be an auxiliary indicator, together with prostate-specific
      antigen (PSA), to monitor PCa disease progression.

PMID- 21894432
TI  - Comparison of peptide cancer signatures identified by mass spectrometry in serum
      of patients with head and neck, lung and colorectal cancers: association with
      tumor progression.
AB  - Mass spectrometry-based analyses of the low-molecular-weight fraction of serum
      proteome allow identifying proteome profiles (signatures) that are potentially
      useful in detection and diagnostics of cancer. Here we compared serum proteome
      profiles of healthy donors and patients with three different types of cancer
      aiming to identify peptide signatures that were either common for all cancer
      samples or specific for cancer type. Blood samples were collected before start of
      the therapy from patients with head and neck squamous cell cancer, colorectal
      adenocarcinoma and non-small cell lung cancer, and from a corresponding group of
      healthy volunteers. Mass profiles of the serum proteome were recorded in the
      range between 2 and 13 kDa using MALDI-ToF spectrometry and 131 identified
      peptide ions were used for statistical analyses. Similar degrees of overall
      similarities were observed in all intra-group and inter-group analyses when
      general features of serum proteome profiles were compared between individual
      samples. However, classifiers built of selected spectral components allowed
      differentiation between healthy donors and three groups of cancer patients with
      69-74% sensitivity and 82-84% specificity. There were two common peptide species
      (3766 and 5867 Da) with increased levels in all cancer samples. Several spectral
      components permitted differentiation between lung cancer samples and either head
      and neck cancer or colorectal cancer samples, but two latter types of samples
      could not be properly discriminated. Abundance of spectral components that
      putatively corresponded to fragments of serum amyloid A (11511 and 11667 Da) was
      highest in lung cancer samples, yet increased levels of these peptides appeared
      to generally associate with more advanced cancer cases. We concluded that certain
      components of serum peptide signatures are common for different cancer signatures
      and putatively reflect general response of organism to the disease, yet other
      components of such signatures are more specific and most likely correspond to
      clinical stage of the malignancy.

PMID- 21894433
TI  - Treatment with the Chk1 inhibitor Go6976 enhances cisplatin cytotoxicity in SCLC
      cells.
AB  - Acquired chemoresistance is a major obstacle in successful treatment of small
      cell lung cancer (SCLC). DNA damage responses can potentially contribute to
      resistance by halting the cell cycle following exposure to therapeutic agents,
      thereby facilitating repair of drug-induced lesions and protecting tumour cells
      from death. The Chk1 protein kinase is a key regulator in this response. We
      analysed the status of cell cycle checkpoint proteins and the effects of the Chk1
      inhibitor Go6976 on cisplatin toxicity in SCLC cell lines. IC50s for cisplatin
      were determined using the MTT assay in six SCLC cell lines. Effects on cell cycle
      distribution and apoptosis were determined by flow cytometry and caspase 3
      activation in the presence or absence of the Chk1 inhibitor Go6976. The
      activation of checkpoint proteins was determined by Western blotting. Cell lines
      were divided into chemosensitive and chemoresistant groups on the basis of our
      results. While checkpoint responses were detected in these cell lines through
      Western blotting, some of these responses were delayed or weaker than those seen
      in other cell types in response to DNA damage and replication stress. Go6976
      significantly (p<0.05) enhanced the levels of apoptosis seen in response to a
      clinically relevant dose of cisplatin (<6 uM) and decreased drug-induced G2
      arrest in chemosensitive cells. Our data suggest a role for Chk1 in
      chemoresistance of SCLC cells and a potential approach to improve initial
      response of SCLC to cisplatin therapy.

PMID- 21894434
TI  - Ultra-violet irradiation induces apoptosis via mitochondrial pathway in
      pancreatic cancer cells.
AB  - Pancreatic cancer is a highly lethal disease and gemcitabine is considered to be
      the standard of care for the treatment of advanced pancreatic cancer. However,
      the outcome of the patients treated with gemcitabine is still unstatisfactory and
      further development of new treatments is required. We recently found that short
      wavelength ultra-violet (UV-C) suppresses cell proliferation with downregulation
      of epidermal growth factor receptor (EGFR) in human pancreatic cancer cells, but
      not in normal pancreatic epithelial (PE) cells. In this study, we investigated
      the effect of UV-C on apoptosis in several cell lines derived from the pancreas.
      UV-C induced poly(ADP-ribose) polymerase (PARP) cleavage, which is a marker of
      cells undergoing apoptosis, in Panc1, MiaPaca2, KP3 and BxPC3 pancreatic cancer
      cells, but not in PE cells. We also observed similar effects in Hoechst 33258
      staining, which shows DNA fragmentation. While p53, a tumor suppressor protein,
      plays a critical role in UV-C-induced cell damage, we did not observe the
      correlation between the sensitivity to UV-C and p53 status. Thapsigargin, an
      agent that promotes endoplasmic reticulum (ER) stress by depletion of lumenal
      calcium stores, as well as cis-diamineplatinum (II) dichloride, a classical anti
      cancer drug that causes DNA damage, induced PARP cleavage even in PE cells.
      Moreover, UV-C-induced apoptosis in Panc1 and KP3 cells was associated with the
      release of cytochrome c, indicating that it was mediated via mitochondrial
      pathway. Taken together, UV-C has a potent anti-cancer effect on pancreatic
      cancer cells without adverse effect on normal cells and it could be useful for
      the treatment of human pancreatic cancers.

PMID- 21894435
TI  - Loss of 6q or 8p23 is associated with the total number of DNA copy number
      aberrations in adenoid cystic carcinoma.
AB  - We analyzed 10 adenoid cystic carcinomas (ACCs) of the salivary glands by array
      based comparative genomic hybridization (a-CGH) using DNA chips spotted with
      4,030 bacterial artificial chromosome clones. After the data smoothing procedure
      was applied, a total of 88 DNA copy number aberrations (DCNAs) were detected. The
      frequent (>=30%) DCNAs were loss of 6q23-27 and 8p23, and gains of 6p, 6q23, 8p23
      and 22q13. High-level gains were detected on 12q15, including MDM2 in two cases.
      These two cases showed an immunohistochemically high-level (>50%) expression of
      MDM2 and a low-level expression of p53 (<20%). Furthermore, the total number of
      DCNAs was significantly greater in ACCs with loss of 6q compared to other ACCs,
      and in ACCs without the loss of 8p23 compared to other ACCs, respectively.
      Although limitations exist, a-CGH detected several candidate chromosomal
      imbalances associated with accumulation of DCNAs in ACCs.

PMID- 21894436
TI  - Differential expression of up-regulated cofilin-1 and down-regulated cofilin-2
      characteristic of pancreatic cancer tissues.
AB  - Pancreatic cancer (PC) is one of the most deadly malignant tumors. The aim of
      this study was to identify potential biomarkers for PC. Using two-dimensional gel
      electrophoresis and liquid chromatography-tandem mass spectrometry, the proteomic
      profiles of pancreatic cancerous and non-cancerous tissues from ten patients with
      PC were compared. One of the numerous spots that showed stronger intensity in
      cancerous compared to non-cancerous tissues was identified as non-muscle cofilin
      (cofilin-1). This up-regulation was validated by Western blot analysis. It is
      noteworthy that Western blot analysis showed significantly lower expression of
      muscle cofilin (cofilin-2) in pancreatic cancerous tissues compared to non
      cancerous tissues. This is the first time that cofilin isoforms (cofilin-1/2)
      have been identified to be differentially expressed in pancreatic cancerous
      tissues. Therefore, cofilin isoforms may serve as candidates for clinically
      useful biomarkers or therapeutic targets for PC.

PMID- 21894437
TI  - A PVP-extract fungal protein of Omphalia lapideacens and its antitumor activity
      on human gastric tumors and normal cells.
AB  - Omphalia lapidescens is an important medicinal fungus as well as traditional
      Chinese medicine used for disease treatment. It is mainly used as a vermifuge for
      anthelmintic therapy, but it has not been hitherto reported to possess antitumor
      activity. In this study, a purified bioactive protein in O. lapidescens (pPeOp)
      was obtained using polyvinylpyrrolidone (PVP) followed by gel filtration
      chromatography. To evaluate the in vitro antitumor activity of pPeOp in human
      gastric tumor cells (MC-4 and SGC-7901) and normal cells (MC-1), MTT assay and
      FCM assay were used and the morphological changes, cell viability, cell death
      rate and cell apoptosis rate of MC-4, SGC-7901 and MC-1 cells were estimated. The
      results showed that pPeOp could significantly reduce the cell viability of MC-4
      and SGC-7901 cells in a concentration-dependent manner, with IC50 values of
      236.05 and 156.28 ug/ml, respectively. The morphological observation also
      indicated a similar result. In FCM assays, a significant increase of cell death
      rate and cell apoptosis rate of the tumor cells were observed, indicating
      probable necrosis-inducing effects and/or apoptosis-inducing effects of pPeOp.
      Importantly, there was no significant effect of pPeOp on MC-1 cells in each
      assay, showing that pPeOp has no adverse effects on the normal cells. In
      conclusion, pPeOp is a newly discovered bioactive protein in O. lapidescens and
      this is the first report on antitumor activity of such a fungal protein. This may
      provide a meaningful basis for developing a new protein drug for treatment
      against cancer, especially gastric cancer.

PMID- 21894438
TI  - Overexpression of CD26/DPPIV in mesothelioma tissue and mesothelioma cell lines.
AB  - Mesothelioma, a highly aggressive cancer with poor prognosis and refractory to
      currently available therapies show increasing trends of its incidence in Japan
      and other developing countries. Although surgery is a gold standard for patients
      with early mesothelioma, most patients with advanced disease are not suitable for
      surgical resection and have option of palliative chemotherapy alone. One of the
      new treatment strategies for mesothelioma, the humanized anti-CD26 monoclonal
      antibody therapy is under development. CD26, a 110-kDa transmembrane glycoprotein
      with known dipeptidyl peptidase IV activity, plays a role in tumor development
      and its expression was reported in various human malignancies. This study
      determined the preliminary selection criteria for humanized monoclonal anti-CD26
      antibody therapy. Eighty-one epithelioid (49 differentiated and 32 less
      differentiated), 34 sarcomatoid, 19 biphasic mesothelioma and 8 mesothelioma cell
      lines were immunohistochemically examined using 8 different commercially
      available anti-CD26 antibodies for membranous and cytoplasmic expression. The
      cytoplasmic expression of CD26 was observed in all histological types of
      mesothelioma, while the membranous expression of CD26 was found in 88% of
      differentiated and 69% of less differentiated epithelioid mesothelioma, and none
      of sarcomatoid mesothelioma with anti-CD26 antibodies with rabbit polyclonal anti
      DPP4 antibody and similar results were also obtained with goat polyclonal anti
      DPP4/CD26 antibody. These antibodies absorbed with soluble human CD26 proteins do
      not show CD26 expression in mesothelioma tissue, suggesting these two antibodies
      localize true CD26 protein. Seven mesothelioma cell lines, including sarcomatoid
      types, also showed membranous expression of CD26 in cellblock preparation. CD26
      vector transfection to CD26-negative MSTO-211H cells showed membranous expression
      of CD26 by flow cytometry, but not in tumor developed in NOD/SCID mice with
      inoculation of CD26 vector transfected MSTO-211H cells. We found that both rabbit
      and goat polyclonal antibodies are suitable for immunohistochemical evaluation of
      membranous expression of CD26 in mesothelioma.

PMID- 21894439
TI  - Expression patterns of the tumor suppressor PDCD4 and correlation with beta
      catenin expression in gastric cancers.
AB  - The expression patterns of PDCD4, a tumor suppressor, and beta-catenin were
      immunohistologically investigated in gastric carcinoma tissues. In normal gastric
      tissues, PDCD4 was strongly expressed in the cell nuclei, but weakly expressed in
      the cytoplasm. In gastric adenocarcinoma tissues, nuclear PDCD4 expression was
      decreased, while cytoplasmic PDCD4 expression was unchanged or somewhat
      increased. In gastric signet ring cell carcinoma tissues, PDCD4 expression
      patterns were different from the expression patterns of the adenocarcinoma
      tissues, and PDCD4 was localized in the nuclei of the carcinoma cells as a belt
      in the middle of the epithelial layer. The nuclear localization of PDCD4 in the
      adenocarcinoma tissues was correlated with the membrane localization of beta
      catenin, the activation of which stimulates invasion of colon cancer cells. PDCD4
      expression was correlated with beta-catenin expression in gastric carcinoma cell
      lines, but not with E-cadherin, as the binding partner in the cell membrane.

PMID- 21894441
TI  - Chromosome aberrations in peripheral blood lymphocytes of individuals living in
      high background radiation areas of Ramsar, Iran.
AB  - In order to investigate the biological effects of exposure to low-dose radiation
      and to assess the dose-effect relationship in residents of high background
      radiation areas (HBRAs) of Ramsar, cytogenetic investigation of unstable-type
      aberrations was performed in 15 healthy elderly women in a HBRA of Ramsar, Talesh
      mahalle, and in 10 elderly women living in a nearby control area with normal
      background radiation. In total, 77,714 cells were analyzed; 48,819 cells in HBRA
      residents and 28,895 cells in controls. On average, 3,108 cells per subject were
      analyzed (range 1,475-5,007 cells). Significant differences were found in the
      frequency of dicentric plus centric rings in 100 cells (0.207 +/- 0.103 vs. 0.047
      +/- 0.027, p < 0.0005), total chromosome-type aberrations per 100 cells (0.86 +/-
      0.44 vs. 0.23 +/- 0.17, p < 0.0005), and chromatid-type aberrations per 100 cells
      (3.31 +/- 2.01 vs. 1.66 +/- 0.63, p = 0.01) by the Mann-Whitney U test between
      HBRA and the control, respectively. Using chromosomal aberrations as the main
      endpoint to assess the dose-effect relationship in residents of HBRAs in Ramsar,
      no positive correlation was found between the frequency of dicentric plus centric
      ring aberrations and the cumulative dose of the inhabitants estimated by direct
      individual dosimetry; however, obvious trends of increase with age appeared in
      the control group. Based on these results, individuals residing in HBRAs of
      Ramsar have an increased frequency of detectable abnormalities in unstable
      aberrations.

PMID- 21894440
TI  - Mutation induction by inhaled radon progeny modeled at the tissue level.
AB  - The observable responses of living systems to ionizing radiation depend on the
      level of biological organization studied. Understanding the relationships between
      the responses characteristic of the different levels of organization is of
      crucial importance. The main objective of the present study is to investigate how
      some cellular effects of radiation manifest at the tissue level by modeling
      mutation induction due to chronic exposure to inhaled radon progeny. For this
      purpose, a mathematical model of the bronchial epithelium was elaborated to
      quantify cell nucleus hits and cell doses. Mutagenesis was modeled considering
      endogenous as well as radiation-induced DNA damages and cell cycle shortening due
      to cell inactivation. The model parameters describing the cellular effects of
      radiation are obtained from experimental data. Cell nucleus hits, cell doses, and
      mutation induction were computed for the activity hot spots of the large bronchi
      at different exposures. Results demonstrate that the mutagenic effect of densely
      ionizing radiation is dominated by cell cycle shortening due to cell inactivation
      and not by DNA damages. This suggests that radiation burdens of non-progenitor
      cells play a significant role in mutagenesis in case of protracted exposures to
      densely ionizing radiation. Mutation rate as a function of dose rate exhibits a
      convex shape below a threshold. This threshold indicates the exhaustion of the
      tissue regeneration capacity of local progenitor cells. It is suggested that
      progenitor cell hyperplasia occurs beyond the threshold dose rate, giving a
      possible explanation of the inverse dose-rate effect observed in the epidemiology
      of lung cancer among uranium miners.

PMID- 21894442
TI  - IL-17 receptor and its functional significance in psoriatic arthritis.
AB  - To delineate the functional significance of IL-17 Receptor (IL-17RA) and
      characterize the IL-17 producing T cell (Th17) subpopulation in psoriatic
      arthritis (PsA). Mononuclear cells from blood and synovial fluid (SF) were
      obtained from PsA (n=20), rheumatoid arthritis (RA, n=20) and osteoarthritis (OA,
      n=20) patients. Synoviocytes (FLS) were isolated from the synovium of RA (n=5),
      PsA (n=5) and OA (n=5) patients. IL-17RA expression in FLS was identified by
      western blotting (WB) and flowcytometry. T lymphocytes derived from the SF of
      these patients were studied to identify and phenotype the Th17 cells. The
      functional significance of IL-17RA was determined by evaluating its regulatory
      role on the production of proinflammatory cytokines and endopeptidase. IL-17RA
      expression was found to be significantly higher in FLS of RA (15.7%+/-4.9) and
      PsA (4.5%+/-0.9) in comparison to OA (1.14%+/-0.9). Western blot analyses showed
      that the relative intensity (RI) of IL-17RA protein was higher in RA and PsA
      compared to OA (Fisher exact, P<0.01). A significant enrichment of IL-17
      producing CD4+ T cells (7.9%+/-2.8) was observed in the SF of PsA patients
      compared to that of OA patients (P<.001). Compared to OA-FLS, recombinant IL-17
      induced higher levels of IL-6, IL-8, and MMP-3 production in PsA-FLS. Blockage of
      IL-17RA with an anti-IL-17RA antibody inhibited the production of IL-6, IL-8, and
      MMP-3. This is the first report to demonstrate the functional significance of IL
      17RA in PsA. Results of this study support the hypothesis that IL-17RA blocking
      antibodies have the potential to be a therapeutic option for psoriatic arthritis.

PMID- 21894443
TI  - Testosterone-dependent increase in blood pressure is mediated by elevated Cyp4A
      expression in fructose-fed rats.
AB  - Endothelial dysfunction and increased blood pressure following insulin resistance
      play an important role in the development of secondary cardiovascular
      complications. The presence of testosterone is essential for the development of
      endothelial dysfunction and increased blood pressure. Testosterone regulates the
      synthesis of vasoconstrictor eicosanoids such as 20-hydroxyeicosatetranoic acid
      (20-HETE). In a series of studies, we examined: (1) the role of the androgen
      receptor in elevating blood pressure and (2) the effects of Cyp4A-catalyzed 20
      HETE synthesis on vascular reactivity and blood pressure in fructose-fed rats. In
      the first study, intact and castrated male rats were made insulin resistant by
      feeding fructose for 9 weeks following which their superior mesenteric arteries
      (SMA) were isolated and examined for changes in endothelium-dependent relaxation
      in the presence and absence of 1-aminobenzotriazole (ABT) and N-methylsulfonyl
      12,12-dibromododec-11-enamide (DDMS), which are inhibitors of 20-HETE synthesis.
      In another study, male rats were treated with either ABT or the androgen receptor
      blocker, flutamide, following which changes in insulin sensitivity, blood
      pressure, and vascular Cyp4A expression were measured. In the final study,
      HET0016, which is a more selective inhibitor of 20-HETE synthesis, was used to
      confirm our earlier findings. Treatment with HET0016 or ABT prevented or
      ameliorated the increase in blood pressure. Gonadectomy or flutamide prevented
      the increase in both the Cyp4A and blood pressure. Furthermore, both ABT and DDMS
      improved relaxation only in the intact fructose-fed rats. Taken together our
      results suggest that in the presence of testosterone, the Cyp4A/20-HETE system
      plays a key role in elevating the blood pressure secondary to insulin resistance.

PMID- 21894445
TI  - Age-dependent modulation of sensory reweighting for controlling posture in a
      dynamic virtual environment.
AB  - Older adults require more time to reweight sensory information for maintaining
      balance that could potentially lead to increased incidence of falling in rapidly
      changing or cognitively demanding environments. In this study, we manipulated the
      visual surround information during a collision avoidance task in order to
      investigate how young and elderly adults engage in sensory reweighting under
      conditions of visual anticipation. Sixteen healthy elderly (age: 71.5 +/- 4.9
      years; height: 159.3 +/- 6.6 cm; mass: 73.3 +/- 3.3 kg) and 20 young (age: 22.8
      +/- 3.3 years; height: 174.4 +/- 10.7 cm; mass: 70.1 +/- 13.9 kg) participants
      stood for 240 s on a force platform under two experimental conditions: quiet
      standing and standing while anticipating randomly approaching virtual objects to
      be avoided. During both tasks, the visual surround changed every 60 s from a
      stationary virtual scene (room) to either a moving room or darkness and then back
      to a stationary scene to evoke sensory reweighting processes. In quiet standing,
      elderly showed greater sway variability and were more severely affected by the
      removal or degradation of visual surround information when compared to young
      participants. During visual anticipation, sway variability was not different
      between the age groups. In addition, both young and elderly participants were
      similarly affected by the degradation or removal of the visual surround. These
      findings suggest that sensory reweighting in a dynamic virtual environment that
      evokes visual anticipation interacts with postural state anxiety regardless of
      age. Elderly show less efficient sensory reweighting in quiet standing due to
      greater visual field dependence possibly associated with fear of falling.

PMID- 21894446
TI  - Mediterranean diet reduces senescence-associated stress in endothelial cells.
AB  - This paper aims to study the effects of the oxidative stress induced by quality
      and quantity of dietary fat on cellular senescence. Twenty elderly subjects
      consumed three diets, each for 4 weeks: a saturated fatty acid diet (SFA), a low
      fat and high-carbohydrate diet (CHO-ALA), and a Mediterranean diet (MedDiet)
      enriched in monounsaturated fatty acid following a randomized crossover design.
      For each diet, we investigated intracellular reactive oxidative species (ROS),
      cellular apoptosis and telomere length in human umbilical endothelial cells
      incubated with serum from each patient. MedDiet induced lower intracellular ROS
      production, cellular apoptosis, and percentage of cell with telomere shortening,
      compared with the baseline and with SFA and CHO-ALA diets. Dietary fat modulates
      the oxidative stress in human endothelial cells. MedDiet protects these cells
      from oxidative stress, prevents cellular senescence and reduces cellular
      apoptosis.

PMID- 21894447
TI  - Are centenarians genetically predisposed to lower disease risk?
AB  - Our study purpose was to compare a disease-related polygenic profile that
      combined a total of 62 genetic variants among (i) people reaching exceptional
      longevity, i.e., centenarians (n = 54, 100-108 years, 48 women) and (ii)
      ethnically matched healthy controls (n = 87, 19-43 years, 47 women). We computed
      a 'global' genotype score (GS) for 62 genetic variants (mutations/polymorphisms)
      related to cardiometabolic diseases, cancer or exceptional longevity, and also
      specific GS for main disease categories (cardiometabolic risk and cancer risk,
      including 36 and 24 genetic variations, respectively) and for exceptional
      longevity (7 genetic variants). The 'global' GS was similar among groups
      (centenarians: 31.0 +/- 0.6; controls 32.0 +/- 0.5, P = 0.263). We observed that
      the GS for hypertension, cancer (global risk), and other types of cancer was
      lower in the centenarians group compared with the control group (all P < 0.05),
      yet the difference became non significant after adjusting for sex. We observed
      significant between-group differences in the frequency of GSTT1 and GSTM1
      (presence/absence) genotypes after adjusting for multiple comparisons. The
      likelihood of having the GSTT1 low-risk (functional) allele was higher in
      centenarians (odds ratio [OR] 5.005; 95% confidence interval [CI], 1.810-13.839),
      whereas the likelihood of having the GSTMI low-risk (functional) allele was
      similar in both groups (OR 1.295; 95% CI, 0.868 -1.931). In conclusion, we found
      preliminary evidence that Spanish centenarians have a lower genetic
      predisposition for cancer risk. The wild-type (i.e., functional) genotype of
      GSTT1, which is associated with lower cancer risk, might be associated with
      exceptional longevity, yet further studies with larger sample sizes must confirm
      these findings.

PMID- 21894448
TI  - Instability of the cellular lipidome with age.
AB  - The human lens nucleus is formed in utero, and from birth onwards, there appears
      to be no significant turnover of intracellular proteins or membrane components.
      Since, in adults, this region also lacks active enzymes, it offers the
      opportunity to examine the intrinsic stability of macromolecules under
      physiological conditions. Fifty seven human lenses, ranging in age from 12 to 82
      years, were dissected into nucleus and cortex, and the nuclear lipids analyzed by
      electrospray ionization tandem mass spectrometry. In the first four decades of
      life, glycerophospholipids (with the exception of lysophosphatidylethanolamines)
      declined rapidly, such that by age 40, their content became negligible. In
      contrast the level of ceramides and dihydroceramides, which were undetectable
      prior to age 30, increased approximately 100-fold. The concentration of
      sphingomyelins and dihydrosphingomyelins remained unchanged over the whole life
      span. As a consequence of this marked alteration in composition, the properties
      of fiber cell membranes in the centre of young lenses are likely to be very
      different from those in older lenses. Interestingly, the identification of age 40
      years as a time of transition in the lipid composition of the nucleus coincides
      with previously reported macroscopic changes in lens properties (e.g., a massive
      age-related increase in lens stiffness) and related pathologies such as
      presbyopia. The underlying reasons for the dramatic change in the lipid profile
      of the human lens with age are not known, but are most likely linked to the
      stability of some membrane lipids in a physiological environment.

PMID- 21894449
TI  - Identification of CD105 (endoglin)-positive stem-like cells in rhabdoid
      meningioma.
AB  - To investigate the tumor-initiating cells (TICs) in rhabdoid meningioma (RM), a
      population of CD105-positive cells isolated from a fresh RM surgical sample was
      analyzed for proliferative activity, self-renewal ability, tumorigenic ability,
      multilineage differentiation potential, as well as chromosomal aberrations. The
      results showed that isolated CD105-positive cells could be maintained for more
      than 50 generations in vitro. These cells exhibited increased proliferative
      activity and single-cell tumor sphere-formation ability compared with CD105
      negative cells. In vivo experiments showed that CD105-positive cells possessed
      much greater potential to reconstitute the original human RM in nude mice as
      compared with CD105-negative cells. Phenotypically, CD105-positive cells shared
      some surface markers with mesenchymal progenitor cells (MPCs), but karyotype
      analysis showed chromosomal abnormalities characteristic of malignant meningioma,
      thus distinguishing them from supportive stroma-derived MPCs. In addition, in
      contrast to CD105-negative cells, CD105-positive cells could differentiate into
      adipocytes and osteocytes in response to specific induction agents. Finally,
      CD105-positive cells with stem-like features were also isolated from xenograft
      tumors. In conclusion, a population of CD105-positive TICs with some traits of
      MPCs was identified in RM and might provide a promising therapeutic target in
      management of malignant meningioma.

PMID- 21894450
TI  - Effects of vibration training on bone metabolism: results from a short-term bed
      rest study.
AB  - The absence of mechanical loading leads to a prompt increase in bone resorption
      measured by bone resorption markers. There is high potential that vibration
      training can positively influence bone metabolism in immobilized subjects, reduce
      the increase in osteoclastic activity and increase bone formation processes. We
      investigated whether vibration training at 20 Hz with an amplitude of 2-4 mm
      influences bone metabolism during immobilization. Eight male subjects (26.4 +/-
      4.9 years; 78.1 +/- 9.5 kg) performed a 14 day bed rest in 6 degrees -head down
      tilt (HDT). Subjects received vibration training for 2 * 5 min/day or a control
      intervention without vibration (crossover design). Calcium excretion and bone
      resorption markers C-telopeptide (CTX) and N-telopeptide (NTX) were analyzed from
      24 h urine samples. Bone formation markers, bone alkaline phosphatase (bAP) and
      procollagen-N propeptide (PINP) were analyzed from fasting blood samples. Our
      results show an increase in bone resorption very early during HDT bed rest in
      both interventions (CTX: p < 0.01; NTX: p < 0.001). Vibration training did not
      have any different effect on bone resorption markers (CTX: p = 0.10; NTX: p =
      0.58), bone formation markers (PINP: p = 0.21; bAP: p = 0.12) and calcium
      excretion (p < 0.64) compared to the control condition. Mere vibration training
      with 20 Hz for 2 * 5 min/day does not prevent increase in bone resorption as
      measured with the described methods in our short-term HDT bed rest.

PMID- 21894451
TI  - Neurophysiological and behavioral effects of a 60 Hz, 1,800 MUT magnetic field in
      humans.
AB  - The effects of time-varying magnetic fields (MF) on humans have been actively
      investigated for the past three decades. One important unanswered question is the
      potential for MF exposure to have acute effects on human biology. Different
      strategies have been used to tackle this question using various physiological,
      neurophysiological and behavioral indicators. For example, researchers
      investigating electroencephalography (EEG) have reported that extremely low
      frequency (ELF, <300 Hz) MF can increase resting occipital alpha rhythm (8-12
      Hz). Interestingly, other studies have demonstrated that human motricity can be
      modulated by ELF MF: a reduction of anteroposterior standing balance or a
      decrease of physiological tremor intensity have been reported as consequences of
      exposure. However, the main limitation in this domain lies in the lack of results
      replication, possibly originating from the large variety of experimental
      approaches employed. Therefore, the present study aimed to investigate the
      effects of a 60 Hz, 1,800 MUT MF exposure on neurophysiological (EEG) and
      neuromotor (standing balance, voluntary motor function, and physiological tremor)
      aspects in humans using a single experimental procedure. Though results from this
      study suggest a reduction of human standing balance with MF exposure, as well as
      an increase of physiological tremor amplitude within the frequency range
      associated with central nervous system contribution, no exposure effect appeared
      on other investigated parameters (e.g., EEG or voluntary motor control). These
      results suggest that 1 h of 60 Hz, 1,800 MUT MF exposure may modulate human
      involuntary motor control without being detected in the cortical electrical
      activity.

PMID- 21894452
TI  - Optimisation of the operational conditions of trichloroethylene degradation using
      Trametes versicolor under quinone redox cycling conditions using central
      composite design methodology.
AB  - Extracellular radicals produced by Trametes versicolor under quinone redox
      cycling conditions can degrade a large variety of pollutant compounds, including
      trichloroethylene (TCE). This study investigated the effect of the agitation
      speed and the gas-liquid phase volume ratio on TCE degradation using central
      composite design (CCD) methodology for a future scale-up to a reactor system. The
      agitation speed ranged from 90 to 200 rpm, and the volume ratio ranged from 0.5
      to 4.4. The results demonstrated the important and positive effect of the
      agitation speed and an interaction between the two factors on TCE degradation.
      Although the volume ratio did not have a significant effect if the agitation
      speed value was between 160 and 200 rpm, at lower speed values, the specific
      pollutant degradation was clearly more extensive at low volume ratios than at
      high volume ratios. The fitted response surface was validated by performing an
      experiment using the parameter combination in the model that maximised TCE
      degradation. The results of the experiments carried out using different biomass
      concentrations demonstrated that the biomass concentration had a positive effect
      on pollutant degradation if the amount of biomass present was lower than 1.6 g
      dry weight l(-1). The results show that the maximum TCE degradation was obtained
      at the highest speed (200 rpm), gas-liquid phase volume ratio (4.4), and a
      biomass concentration of 1.6 g dry weight l(-1).

PMID- 21894453
TI  - A case of meningitis due to Neisseria subflava after ventriculostomy.
AB  - Surgical site infection (SSI) is an emerging problem in all fields of surgery, as
      well as in neurosurgery, with numerous strategies against SSI initiated in many
      countries. In this report, we describe a case of SSI caused by Neisseria subflava
      a month after ventriculostomy placement for acute hydrocephalus. A 53-year old
      man was referred to our hospital, and was diagnosed with a thalamic hemorrhage
      with ventricular rupture. Bilateral ventriculostomies were performed on the day
      of presentation. After intensive care for the acute stage, an SSI at the left
      ventriculostomy site was recognized on the 39th hospital day. The installed
      reservoir and ventricular tube was removed on the 40th hospital day. The CSF cell
      count was 2064/3, and N. subflava was recovered from the CSF culture. N. subflava
      is a common inhabitant found in the human upper respiratory tract, and is
      reported to be a rare cause of meningitis. There is one case report of meningitis
      caused by N. subflava transmitted during myelography from medical staff who did
      not wear facemasks during the procedure. Meningitis caused by N. subflava is
      rare, and transmission via a medical procedure is extremely rare. Although
      reported to be only rarely pathogenic, we must recognize that N. subflava can
      indeed be pathogenic, and can in rare cases be the cause of postoperative
      meningitis.

PMID- 21894454
TI  - Reduction in the incidence of MRSA with use of alcohol-based hand rub solutions
      and gloves.
AB  - Methicillin-resistant Staphylococcus aureus (MRSA) is highly contagious. It is
      spread by direct contact with MRSA-infected people or objects. Healthcare
      workers' hands are the most common vehicle for the transmission of healthcare
      associated pathogens from patient to patient and within the healthcare
      environment. The present study aimed to investigate the correlation between the
      incidence of MRSA among Staphylococcus aureus recovered from clinical culture and
      the use of alcohol-based hand rub solutions or gloves and antimicrobial use
      density (AUD). All data were examined every 6 months between January 2005 and
      June 2008. The increasing use of alcohol-based hand rub solutions was correlated
      with a decreasing incidence of recovery of MRSA from clinical cultures (r(2) =
      0.58). A statistically significant (P < 0.05) correlation (r(2) = 0.68) was
      observed between glove use and the incidence of MRSA. On the other hand, we did
      not find any correlation between the AUD of each antibiotic group and the
      incidence of MRSA. Thus, we suggest that it is important to use not only alcohol
      based hand rubs, but also gloves, because MRSA is transmitted from patient to
      patient by the hands of healthcare workers.

PMID- 21894455
TI  - A report from the committee on microbroth dilution antimicrobial susceptibility
      testing : issues in antimicrobial susceptibility testing of Haemophilus
      influenzae: a comparison of the Japanese Society of Chemotherapy lysed horse
      blood and the CLSI HTM broth microdilution methods.

PMID- 21894456
TI  - Bilateral circumscribed choroidal hemangioma with retinal and choroidal venous
      abnormalities.

PMID- 21894457
TI  - Sarcomatoid Carcinoma of the Anorectal Junction: Struggling with an Extremely
      Rare Tumor.

PMID- 21894458
TI  - Hepatoid Adenocarcinoma of the Lung: A Case Report and Literature Review.

PMID- 21894459
TI  - Association of type 2 diabetes and colon adenomas.
AB  - INTRODUCTION: Type 2 diabetes mellitus (DM) is associated with hyperinsulinemia,
      which may lead to increased risk of carcinogenesis by increasing insulin-like
      growth factor-1 level. In this study, we sought to determine the association
      between type 2 DM and colon adenomas. METHODS: In this retrospective case-control
      study, all the colonoscopies performed in an urban medical center during a 3-year
      period were reviewed. Patients with adenomatous polyps were considered as cases
      (n = 261). Age- and sex-matched controls with a 2:1 ratio were selected (n =
      522). Among diabetic subjects, the association of different anti-diabetic
      medications and HbA1C level with high-risk adenoma features was analyzed.
      RESULTS: Type 2 DM was significantly associated with colon adenomas (odds ratio
      (OR) = 1.45, 95% confidence interval (CI) = 1.05-2.01, p = 0.024). Exposure to
      insulin (OR = 1.734, 95% CI = 1.13-2.65, p = 0.013) and thiazolidinediones (OR =
      2.83, 95% CI = 1.28-6.26, p = 0.01) was associated with developing adenomas.
      Neither the type of antidiabetic medication nor the level of HbA1C was a
      predictor for high-risk adenomas. Smoking (OR = 1.47, 95% CI = 1.07-2.02, p =
      0.02), use of aspirin (OR = 1.59, 95% CI = 1.15-2.20, p = 0.005), and statins (OR
      = 1.54, 95% CI = 1.13-2.10, p = 0.007) appeared to increase the risk of adenomas.
      CONCLUSION: This study shows a significant association between type 2 DM and
      colon adenomas. Establishing this association may lead to inclusion of diabetic
      patients in the high-risk group for developing colorectal cancer.

PMID- 21894460
TI  - Photosynthetic energy storage efficiency in Chlamydomonas reinhardtii, based on
      microsecond photoacoustics.
AB  - Using a novel, pulsed micro-second time-resolved photoacoustic (PA) instrument,
      we measured thermal dissipation and energy storage (ES) in the intact cells of
      wild type (WT) Chlamydomonas reinhardtii, and mutants lacking either PSI or PSII
      reaction centers (RCs). On this time scale, the kinetic contributions of the
      thermal expansion component due to heat dissipation of absorbed energy and the
      negative volume change due to electrostriction induced by charge separation in
      each of the photosystems could be readily distinguished. Kinetic analysis
      revealed that PSI and PSII RCs exhibit strikingly different PA signals where PSI
      is characterized by a strong electrostriction signal and a weak thermal expansion
      component while PSII has a small electrostriction component and large thermal
      expansion. The calculated ES efficiencies at ~10 MUs were estimated to be 80 +/-
      5 and 50 +/- 13% for PSII-deficient mutants and PSI-deficient mutants,
      respectively, and 67 +/- 2% for WT. The overall ES efficiency was positively
      correlated with the ratio of PSI to PSI + PSII. Our results suggest that the
      shallow excitonic trap in PSII limits the efficiency of ES as a result of an
      evolutionary frozen metabolic framework of two photosystems in all oxygenic
      photoautotrophs.

PMID- 21894461
TI  - Role of Src in breast cancer cell migration and invasion in a breast cell/bone
      derived cell microenvironment.
AB  - The preferential metastasis of breast cancer cells to bone comprises a complex
      set of events including homing and preferential growth, which may require unique
      factors produced by bone or other cells in the immediate microenvironment. In
      this study, an in vitro co-culture system composed of bone mesenchymal stem cells
      and breast cancer cell lines is used to examine the role of Src kinase on breast
      cancer cell migration and invasion in the presence of bone-derived cells. This
      research shows that Src kinase activity in breast cancer cell lines with either
      high or low levels of endogenous Src activity is increased by bone-derived cell
      conditioned medium but not HS68 fibroblast-conditioned medium. Breast cancer
      cells exhibit enhanced migration in co-culture with bone-derived cells but not
      HS68 fibroblasts or no co-cultured cells. Inhibition of Src kinase activity using
      the inhibitors PP2 or saracatinib or using siRNA abrogates the preferential
      migration of the breast cancer cell lines in response to bone-derived cells.
      Inhibition of Src activity with saracatinib does not have any significant effect
      on breast cancer cell invasion in the presence of bone-derived cells. Factors are
      identified that are produced preferentially by bone-derived cells over HS68 cells
      that may impact breast cancer cell behavior. This research implicates Src kinase
      as an important effector of bone-derived cell signals on breast cancer cell
      migration.

PMID- 21894462
TI  - Comparative analysis of involvement of UGT1 and UGT2 splice variants of UDP
      galactose transporter in glycosylation of macromolecules in MDCK and CHO cell
      lines.
AB  - Nucleotide sugar transporters deliver nucleotide sugars into the Golgi apparatus
      and endoplasmic reticulum. This study aimed to further characterize mammalian UDP
      galactose transporter (UGT) in MDCK and CHO cell lines. MDCK-RCA(r) and CHO-Lec8
      mutant cell lines are defective in UGT transporter, although they exhibit some
      level of galactosylation. Previously, only single forms of UGT were identified in
      both cell lines, UGT1 in MDCK cells and UGT2 in CHO cells. We have identified the
      second UGT splice variants in CHO (UGT1) and MDCK (UGT2) cells. Compared to UGT1,
      UGT2 is more abundant in nearly all examined mammalian tissues and cell lines,
      but MDCK cells exhibit different relative distribution of both splice variants.
      Complementation analysis demonstrated that both UGT splice variants are necessary
      for N- and O-glycosylation of proteins. Both mutant cell lines produce
      chondroitin-4-sulfate at only a slightly lower level compared to wild-type cells.
      This defect is corrected by overexpression of both UGT splice variants. MDCK
      RCA(r) mutant cells do not produce keratan sulfate and this effect is not
      corrected by either UGT splice variant, overexpressed either singly or in
      combination. Here we demonstrate that both UGT splice variants are important for
      glycosylation of proteins. In contrast to MDCK cells, MDCK-RCA(r) mutant cells
      may possess an additional defect within the keratan sulfate biosynthesis pathway.

PMID- 21894463
TI  - Discovering the distinct inhibitory effects between C4-epimeric glycosyl amino
      acids: new insight into the development of protein tyrosine phosphatase
      inhibitors.
AB  - There has been increasing interest in the development of drug candidates based on
      sugar templates that possess rich structural and, especially, configurational
      diversities. We disclose herein that the epimeric identity between methyl 3,4-bis
      phenylalanyl/tyrosinyl triazolyl-alpha-D-galactopyranoside and glucopyranoside
      may lead to their distinct inhibitory effects on specific protein tyrosine
      phosphatases (PTPs). Subsequently performed molecular docking study elucidated
      the plausible binding behaviors of the more potent galactosyl inhibitors with
      their primary PTP target, i.e. Cell Division Cycle 25B (CDC25B) phosphatase.

PMID- 21894464
TI  - Characterization of chondroitin sulfate from deer tip antler and osteogenic
      properties.
AB  - Deer antler is a highly regenerative tissue that involves cellular
      differentiation, osteogenesis and ossification processes. Chondroitin sulfate is
      the major glycosaminoglycan contained in antler connective tissue and has been
      isolated from cartilaginous antler by 4 M GuHCl extraction, gradient
      ultracentrifugation and chromatography techniques. We examined the disaccharide
      composition by 2-AB labeling and anion exchange HPLC analysis of the three
      resultant fractions (high, medium and low density fractions). The high density
      fraction consists of A-unit and D-unit disaccharide in the ratio of 1:1, whereas,
      the CS disaccharide composition ratio of A- unit:C-unit:D-Unit:E-unit contained
      in medium and low density fractions are 3:4:3:1 and 2:2:2:1, respectively. The
      only intact CS oligosaccharides of the medium density fraction upregulated gene
      expression of bone-specific proteins of a human osteoblastic cell line
      (hFOB1.19). Thus, CS oligosaccharides from cartilaginous deer antler, with their
      oversulfated chondroitin sulfate composition, demonstrated the physiological
      properties and may be good candidates for osteogenetic agents in humans.

PMID- 21894465
TI  - Interleukin-15 affects differentiation and apoptosis in adipocytes: implications
      in obesity.
AB  - Interleukin-15 (IL-15) is an anabolic factor for skeletal muscle and several
      reports have described its important role as a regulator of energy homeostasis.
      In this study, we analyzed the effects of IL-15 on adipocyte differentiation
      using the 3T3-L1 preadipose cell line. The data show that IL-15 tends to reduce
      the rate of adipocyte proliferation, induces apoptosis, and partially stops
      differentiation. The signaling molecules behind these actions of the cytokine on
      adipose cells are: p42/p44 MAPK (which seem to be associated with the reduced
      rate of proliferation induced by the cytokine), STAT5 (which is related to the
      actions of IL-15 on differentiation), and SAPK/JNK (which are related to the
      increased apoptosis induced by IL-15). In conclusion, using the 3T3-L1 adipocyte
      cell line, the results presented here show that IL-15 exerts important effects on
      differentiation, proliferation and apoptosis. Altogether, the results presented
      here reinforce the idea that IL-15 is an important mediator that regulates
      adipose size and, therefore, the role of the cytokine in affecting body weight
      and obesity deserves additional studies.

PMID- 21894466
TI  - Distribution of Hordoindoline genes in the genus Hordeum.
AB  - Hordoindoline (Hin) genes, which are known to comprise Hina, Hinb-1, and Hinb-2,
      are associated with grain hardness in barley. However, the interspecific
      variation in the Hin genes in the genus Hordeum has not been studied in detail.
      We examined the variation in Hin genes and used it to infer the phylogenetic
      relationships between the genes found in two H. vulgare subspecies (cultivated
      barley and H. vulgare subsp. spontaneum) and 10 wild relatives (H. bogdanii, H.
      brachyantherum, H. bulbosum, H. chilense, H. comosum, H. marinum, H. murinum, H.
      patagonicum, H. pusillum, and H. roshevitzii). The Hina and Hinb genes of these
      species were amplified by PCR. We found two Hinb genes in three wild species (H.
      bogdanii, H. brachyantherum, and H. roshevitzii) and preliminarily named them
      Hinb-A and Hinb-B. Cluster analysis showed that the 17 Hinb genes present in
      Hordeum formed two distinct clusters (named A and B). Seven Hinb genes were
      included in Cluster-A, and 10 Hinb genes were included in Cluster-B. All Hinb-A
      genes were included in Cluster-A, while all of the Hinb-B genes were included in
      Cluster-B. In contrast, the Hinb-1 and Hinb-2 genes in H. vulgare were included
      in Cluster-B. These results suggest that the Hinb genes duplicated during the
      early stages of diversification in the genus Hordeum. On the other hand, the Hinb
      1 and Hinb-2 genes in H. vulgare seem to have been generated by a duplication of
      the Hinb gene after the split of the lineages leading to H. vulgare and H.
      bulbosum.

PMID- 21894467
TI  - Identification of qSOR1, a major rice QTL involved in soil-surface rooting in
      paddy fields.
AB  - Specific Indonesian lowland rice (Oryza sativa L.) cultivars elongate thick
      primary roots on the soil surface of paddy fields. To clarify the genetic factors
      controlling soil-surface rooting, we performed quantitative trait locus (QTL)
      analyses using 124 recombinant inbred lines (RILs) derived from a cross between
      Gemdjah Beton, an Indonesian lowland rice cultivar with soil-surface roots, and
      Sasanishiki, a Japanese lowland rice cultivar without soil-surface roots. These
      cultivars and the RILs were tested for soil-surface rooting in a paddy field. We
      identified four regions of chromosomes 3, 4, 6, and 7 that were associated with
      soil-surface rooting in the field. Among them, one major QTL was located on the
      long arm of chromosome 7. This QTL explained 32.5-53.6% of the total phenotypic
      variance across three field evaluations. To perform fine mapping of this QTL, we
      measured the basal root growth angle of crown roots at the seedling stage in
      seven BC(2)F(3) recombinant lines grown in small cups in a greenhouse. The QTL
      was mapped between markers RM21941 and RM21976, which delimit an 812-kb interval
      in the reference cultivar Nipponbare. We have designated this QTL qSOR1
      (quantitative trait locus for SOIL SURFACE ROOTING 1).

PMID- 21894468
TI  - The effect of insurance status on outcomes after partial nephrectomy.
AB  - BACKGROUND: Privately insured patients may have favorable health outcomes when
      compared to those covered by federally funded initiatives. This study explored
      the effect of insurance status on five short-term outcomes after partial
      nephrectomy (PN). METHODS: Within the Health Care Utilization Project Nationwide
      Inpatient Sample (NIS), we focused on PNs performed between 1998 and 2007. We
      tested the rates of in-hospital mortality, blood transfusions, prolonged length
      of stay, as well as intraoperative and postoperative complications, stratified
      according to insurance status. Multivariable logistic regression analyses fitted
      with general estimation equations for clustering among hospitals further adjusted
      for confounding factors. RESULTS: Overall, 8,513 PNs were identified. Of those,
      most patients were privately insured (53.5%), followed by Medicare (37.5%),
      uninsured (4.6%) and Medicaid (4.4%). Medicare and Medicaid patients had higher
      rates of transfusions (P < 0.001) and overall postoperative complications (P <
      0.001). In multivariable analyses, when compared to privately insured patients,
      Medicaid patients had higher rates of transfusions (OR = 1.91, P < 0.001) and
      prolonged length of stay (OR = 1.49, P < 0.001). Medicare patients had higher
      rates of overall postoperative complications (OR = 1.24, P = 0.015) and length of
      stay beyond the median (OR = 1.4, P < 0.001). CONCLUSION: Patients with private
      insurance undergoing PN have better short-term outcomes, when compared to their
      publicly insured counterparts.

PMID- 21894469
TI  - Update in adult urinary tract infection.
AB  - Urinary tract infection remains a common problem for many populations. Recent
      studies have expanded our understanding of the host innate immune response and
      its role in the familial association observed for recurrent uncomplicated urinary
      tract infection in healthy women. Therapeutic management for uncomplicated
      infection has been compromised by increasing antimicrobial resistance,
      particularly global dissemination of the CTXM-15 extended spectrum beta-lactamase
      (ESBL) producing Escherichia coli ST-131 strain. Prevention strategies exploring
      non-antimicrobial approaches continue to show limited promise, and approaches to
      limit empiric antimicrobials are now being explored. For complicated urinary
      tract infection, increasing antimicrobial resistance limits therapeutic options
      for many patients. In addition to ESBL producing E. coli, NDM-1 E. coli and
      Klebsiella pneumoniae and other resistant Gram negatives, such as Acinetobacter
      species, are being isolated more frequently. There has been renewed interest in
      catheter-acquired urinary tract infection, the most common health-care associated
      infection, with several recent evidence-based guidelines for infection prevention
      available. However, technologic progress in development of adherence-resistant
      catheter materials remains disappointing.

PMID- 21894470
TI  - Unapproved drugs in the United States and the Food and Drug Administration.
AB  - Despite more than a century of evolving federal legislation, there remain many
      unapproved drugs on the United States (US) market. This article reviews the
      history of drug approval in the US, beginning with the landmark Pure Food and
      Drug Act of 1906, through to the development of the US Food and Drug
      Administration (FDA). The Pure Food and Drug Act of 1906 was the first
      comprehensive federal legislation covering drug regulation. Intervening
      legislation, such as the Federal Food, Drug, and Cosmetic Act of 1938 and
      Kefauver-Harris Amendments in 1962, was later instituted. In June 2006, a century
      after the development of the FDA as an enforcement body, an initiative was
      undertaken to remove unapproved drugs from the marketplace. The Marketed
      Unapproved Drugs-Compliance Policy Guide outlines enforcement policies aimed at
      efficiently and rationally bringing all unapproved and illegally marketed drugs
      into the approval process, or discontinuing their manufacture, distribution, and
      sale. The FDA has been actively pursuing control of unapproved drugs in recent
      years, with an approach concentrating on drug safety to ensure optimal public
      health and consumer protection.

PMID- 21894471
TI  - Gouty arthritis: understanding the disease state and management options in
      primary care.
AB  - Acute gouty arthritis is an inflammatory response triggered by the release of
      monosodium urate crystal deposits into the joint space. The disease is associated
      with debilitating clinical symptoms and functional impairments as well as adverse
      economic and quality-of-life burdens. Because gouty arthritis is typically
      diagnosed and managed in the primary care setting, clinicians require a thorough
      knowledge of the presenting clinical features, risk factors, differential
      diagnoses, and treatment options for appropriate management. Although generally
      effective, the use of currently available therapies to control gouty arthritis is
      challenging because many medications used to treat comorbidities can exacerbate
      gouty arthritis and because current agents are associated with a number of
      adverse events, contraindications, or both. Based on an understanding of the
      underlying inflammatory pathogenesis of gouty arthritis, several new agents are
      being developed that may provide improved efficacy.

PMID- 21894472
TI  - Autoimmune myelofibrosis as the first manifestation of human immunodeficiency
      virus infection in an infant.

PMID- 21894474
TI  - Spindle cell variant of multiple myeloma: immunophenotype and cytogenetics
      abnormalities.

PMID- 21894473
TI  - Reduced intensity conditioning allogeneic hematopoietic stem cell transplant
      could be beneficial to angioimmunoblastic T-cell lymphoma patients with
      hemophagocytic lymphohistiocytosis.

PMID- 21894475
TI  - Circulating IL-17 levels during the peri-transplant period as a predictor for
      early leukemia relapse after myeloablative allogeneic stem cell transplantation.
AB  - IL-17 is involved in inducing and mediating pro-inflammatory responses. The
      association of IL-17 with tumor growth or graft-versus-host disease (GVHD) has
      become a subject of controversy. We hypothesized that serum IL-17 (sIL-17) levels
      during the peri-transplant period may affect alloreactive responses after
      allogeneic stem cell transplantation (SCT). sIL-17 levels of 95 patients with
      leukemia who had undergone myeloablative allogeneic SCT were measured using ELISA
      before conditioning and on day 0, +7, and +14 after transplantation. With a
      median follow-up of 17 months, the overall survival, disease-free survival, non
      relapse mortality, and relapse incidence were 70.9%, 66.3%, 10.3%, and 23.4%,
      respectively. Ten patients relapsed within 180 days (early relapse, 10.5%) post
      transplant. The cumulative incidence of acute GVHD over grade II and chronic GVHD
      was 55.8% and 69.0%, respectively. Analyses using repeated measures of ANOVA and
      mean values of sIL-17 revealed that patients relapsed within 180 days had higher
      sIL-17 levels, whereas no association existed between sIL-17 levels and other
      clinical outcomes, including acute GVHD. Receiver operating characteristic curve
      analyses also revealed that sIL-17 levels were available for the prediction of
      early relapse and that patients with higher sIL-17 levels at each time point had
      a significantly higher early relapse. Multivariate analyses and subgroup analyses
      with only standard disease status suggest the association of sIL-17 levels with
      subsequent early relapse independent of disease status at transplantation. This
      study is the first one demonstrating the early change in sIL-17 during the peri
      transplant period and the association with early relapse in humans.

PMID- 21894476
TI  - Efficacy and safety of micafungin as an empirical antifungal therapy for
      suspected fungal infection in neutropenic patients with hematological disorders.
AB  - This prospective multicenter study was performed to clarify the efficacy and
      safety of micafungin (MCFG) as an empirical antifungal therapy for suspected
      fungal infection in patients with hematological disorders and neutropenia. Three
      hundred and eighty-eight patients were enrolled; 151 patients with possible
      fungal infection diagnosed by radiological imaging or serological testing and 237
      patients with refractory fever were included in this study. The mean dose and
      duration of treatment with MCFG were 154.6 mg/day and 14.0 days, respectively.
      The clinical response rate for patients with possible fungal infection and
      refractory fever was 60.1% and 65.3%, respectively. Even in persistent
      neutropenic patients with a neutrophil count of <500/MUL throughout the MCFG
      treatment, the clinical response rate was 46.9%. Ninety-one drug-related adverse
      events (DAEs) were observed in 56 patients (14.4%) and 9 serious DAEs were
      observed in 6 patients (1.5%). Neither daily dose nor duration of MCFG treatment
      affected the incidence of DAEs. It was confirmed that MCFG has adequate clinical
      efficacy and is safe for the treatment of suspected fungal infections in patients
      with hematological disorders and neutropenia.

PMID- 21894477
TI  - Inflammatory pseudotumors mimicking intrahepatic cholangiocarcinoma of the liver;
      IgG4-positivity and its clinical significance.
AB  - BACKGROUND: Inflammatory pseudotumor (IPT) of the liver is a benign condition
      with a good prognosis. However, it is difficult to distinguish clinical and
      radiological findings of IPT from those of malignancies. The aims of this study
      are to determine the clinical, radiological, and pathological characteristics,
      particularly relating to the role of the autoimmune mechanism in the development
      of inflammatory pseudotumours (IPTs) of the liver, and to suggest appropriate
      diagnostic and therapeutic strategy. STUDY DESIGN: The clinical, diagnostic, and
      pathological characteristics including IgG4 immunohistochemical stain and follow
      up data of 22 IPT patients were retrospectively analyzed. RESULTS: The patients
      were 16 men and 6 women with a mean age of 59 years. Fifteen patients (68.2%) had
      associated biliary diseases. Of the 16 patients treated conservatively, the
      masses completely resolved in 10 patients, and reduced in size in 5 patients
      within the first 6 months. The remaining 6 patients were treated by surgical
      resection. IgG4 staining of 17 tissue samples from 22 patients were negative,
      most of the infiltrate being of fibrohistiocytic type, whereas 4 of 5
      lymphoplasmacytic cells of dominant tumors show positive staining of IgG4.
      Although IgG4-related sclerosing cholangitis was mostly of lymphoplasmacytic
      type, other histological and clinical characteristics were similar in both types
      of IPTs. CONCLUSIONS: IPTs of the liver can be diagnosed based on radiological
      and pathological findings by needle biopsy. Although the lymphoplasmacytic type
      of IPTs seems to correspond to IgG4-related disease, as assessed by IgG4
      immunohistochemical stain, its clinical significance is unknown. Although most
      IPTs can be resolved with conservative therapy, surgical resection should be
      considered in cases of uncertain biopsy result, presumed malignant lesion,
      combination with other pathology, or lack of response to conservative management.

PMID- 21894478
TI  - Effect of compost, nitrogen salts, and NPK fertilizers on methane oxidation
      potential at different temperatures.
AB  - The effects of compost, nitrogen salts, and nitrogen-phosphorous-potassium (NPK)
      fertilizers on the methane oxidation potential (MOP) of landfill cover soil at
      various temperatures were assessed. For this, we used batch assays conducted at 5
      degrees C, 15 degrees C, and 25 degrees C with microcosms containing landfill
      cover soil slurries amended with these elements. Results indicated variable
      impacts dependent on the type of amendment and the incubation temperature. For a
      given incubation temperature, MOP varied from one compost to another and with the
      amount of compost added, except for the shrimp/peat compost. With this latter
      compost, independent of the amount, MOP values remained similar and were
      significantly higher than those obtained with other composts. Amendment with most
      of the tested nitrogen salts led to similar improvements in methanotrophic
      activity, except for urea. MOP with NPK fertilizer addition was amongst the
      highest in this study; the minimum value obtained with NPK (20-0-20) suggested
      the importance of P for methanotrophs. MOP generally increased with temperature,
      and nutrient limitation became less important at higher temperatures. Overall, at
      each of the three temperatures tested, MOP with NPK fertilizer amendments
      provided the best results and was comparable to those observed with the addition
      of the shrimp/peat compost. The results of this study provide the first evidence
      of the following: (1) compost addition to improve methanotrophic activity in a
      landfill cover soil should consider the amount and type of compost used and (2)
      the importance of using NPK fertilizers rather than nitrogen salts, in enhancing
      this activity, primarily at low temperatures. One can also consider the potential
      beneficial impact of adding these elements to enhance plant growth, which is an
      advantage for MOP.

PMID- 21894480
TI  - Effect of Mn2+ augmentation on reinforcing aerobic sludge granulation in a
      sequencing batch reactor.
AB  - Two sequencing batch reactors were synchronously operated to investigate the
      effect of manganese (II) (Mn(2+)) augmentation on aerobic granulation. Reactor 1
      (R1) was added with 10 mg/L Mn(2+), while there was no Mn(2+) augmentation in
      reactor 2 (R2). Results showed that R1 had a faster granulation process than R2
      and R1 performed better in chemical oxygen demand (COD) and ammonium nitrogen
      (NH(4)(+)-N) removal efficiencies. Moreover, the mature granules augmented with
      Mn(2+) behaved better on their physical characteristics and size distributions,
      and they also had higher production of extracellular polymeric substances (EPS)
      content. The result of three-dimensional excitation and emission matrix
      fluorescence showed that Mn(2+) had the function of causing organic material
      diversity (especially proteins diversity) in EPS fraction from granules.
      Polymerase chain reaction and denaturing gradient gel electrophoresis techniques
      were employed to analyze the microbial and genetic characteristics in mature
      granules. The results exhibited that Mn(2+) augmentation was mainly responsible
      for the higher microbial diversity of granules from R1 compared with that from
      R2. Uncultured sludge bacterium A16 (AF234726) and Rhodococcus sp. WTZ-R2
      (HM004214) were the major species in R1, while only uncultured sludge bacterium
      A16 (AF234726) in R2. Moreover, there were eight species of organisms found in
      both two aerobic granules, and three species were found only in aerobic granules
      from R1. It could be concluded that Mn(2+) could enhance the sludge granulation
      process and have a key effect role on the biological properties during the sludge
      granulation.

PMID- 21894479
TI  - Microbial synthesis of gold nanoparticles using the fungus Penicillium
      brevicompactum and their cytotoxic effects against mouse mayo blast cancer C 2 C
      12 cells.
AB  - Microorganisms, their cell filtrates, and live biomass have been utilized for
      synthesizing various gold nanoparticles. The shape, size, stability as well as
      the purity of the bio synthesized nanoparticles become very essential for
      application purpose. In the present study, gold nanoparticles have been
      synthesized from the supernatant, live cell filtrate, and biomass of the fungus
      Penicillium brevicompactum. The fungus has been grown in potato dextrose broth
      which is also found to synthesize gold nanoparticles. The size of the particles
      has been investigated by Bio-TEM before purification, following purification and
      after storing the particles for 3 months under refrigerated condition. Different
      characterization techniques like X-ray diffraction, Fourier transform infrared
      spectroscopy, and UV-visible spectroscopy have been used for analysis of the
      particles. The effect of reaction parameters such as pH and concentration of gold
      salt have also been monitored to optimize the morphology and dispersity of the
      synthesized gold nanoparticles. A pH range of 5 to 8 has favored the synthesis
      process whereas increasing concentration of gold salt (beyond 2 mM) has resulted
      in the formation of bigger sized and aggregated nanoparticles. Additionally, the
      cytotoxic nature of prepared nanoparticles has been analyzed using mouse mayo
      blast cancer C(2)C(12) cells at different time intervals (24, 48, and 72 h) of
      incubation period. The cells are cultivated in Dulbecco's modified Eagle's medium
      supplemented with fetal bovine serum with antibiotics (streptopenicillin) at 37
      degrees C in a 5% humidified environment of CO(2). The medium has been
      replenished every other day, and the cells are subcultured after reaching the
      confluence. The viability of the cells is analyzed with 3-(4, 5-dimethylthiazol-2
      yl)-2, 5-diphenyltetrazolium bromide method.

PMID- 21894481
TI  - Detection of invasive Candida albicans infection using a specific (99m)Tc-labeled
      monoclonal antibody for the C. albicans germ tube.
AB  - Accurate diagnosis is critical for effective treatment of the invasive infection
      by Candida albicans. Here, we investigated whether a (99m) technetium (Tc)
      labeled Fab' fragment of the monoclonal antibody specific for the C. albicans
      germ tube could specifically identify an invasive C. albicans infection. The germ
      tube of C. albicans was used as an immunogen to obtain monoclonal antibodies and
      the Fab' fragment of MAb03.2 C1-C2 with highest affinity and specificity was
      labeled with (99m)Tc. In vitro binding assays showed that the labeled Fab'
      preferentially bound to the germ tubes of C. albicans (4.23 +/- 0.17 * 10(2) Bq
      per 1 * 10(7) cells). These values were significantly higher than those for
      blastospores of C. albicans, blastospores of heat-killed C. albicans, Aspergillus
      fumigatus, Staphylococcus aureus, and Escherichia coli (P < 0.05). By using in
      vivo biodistribution and planar imaging with single photon emission computed
      tomography, we demonstrated a significant specific accumulation of radioactivity
      in C. albicans-infected tissues. In summary, (99m)Tc-MAb03.2 C1-C2 Fab' is able
      to specifically accumulate in C. albicans-infected tissues, but not in tissue
      infected with A. fumigatus or bacteria or in a sterile inflammation. This study
      provides a new and specific radiopharmaceutical for the diagnosis of invasive C.
      albicans infections.

PMID- 21894482
TI  - "Wanted!" the effects of reward on face recognition: electrophysiological
      correlates.
AB  - The aim of the present study was to uncover the temporal dynamics of face
      recognition as a function of reward. Event-related potentials (ERPs) were
      recorded during the encoding and the subsequent old/new memory test in response
      to faces that could be associated with a monetary reward. The behavioral results
      showed that faces associated with reward at both encoding and retrieval were
      recognized better than the unrewarded ones. ERP responses highlighted that
      successful encoding predictive of subsequent memory was greater for faces
      associated with reward than for faces without reward-driven motivational
      learning. At retrieval, an early positive-going component was elicited for
      potentially rewarded faces on frontal regions, while the occipito-temporal N170
      component showed priming effects as a function of reward. Later on, larger centro
      parietal ERP components, related to recognition memory, were found selectively
      for reward-associated faces. Remarkably, electrophysiological responses varied in
      a graded manner, with the largest amplitude yielded by faces with double reward,
      followed by faces associated with reward only at encoding. Taken together, the
      present data show that the processing of outcome expectations affects face
      structural encoding and increases memory efficiency, yielding a robust and
      sustained modulation over frontal and temporal areas where reward and memory
      mechanisms operate in conjunction.

PMID- 21894483
TI  - Cognitive impairments caused by oxaliplatin and 5-fluorouracil chemotherapy are
      ameliorated by physical activity.
AB  - RATIONALE: Studies in women with breast cancer, and in animal models, have
      demonstrated that chemotherapy can have a negative impact on cognitive function.
      Which chemotherapy agents cause problems with cognition and the aetiology of the
      impairment is unknown. Furthermore, there is no proven treatment. OBJECTIVES:
      This study aimed to evaluate the effects of 5-fluorouracil (5FU) and oxaliplatin
      (OX) chemotherapy agents commonly used to treat colorectal cancer on cognition in
      laboratory rodents. Furthermore, we assessed physical activity as a potential
      remedy for the observed chemotherapy-induced cognitive deficits. RESULTS: In
      rodents, treatment with 5FU and OX alone impairs memory as measured by novel
      object recognition. But combined treatment appears to have greater detrimental
      effects on hippocampal-dependent tasks, contextual fear recall and spatial
      reference memory (water maze), yet had no effect on cued fear recall, a non
      hippocampal task. These impairments were prevented by 4 weeks of wheel running
      overnight after 5FU/OX treatment. We found a significant interaction between
      chemotherapy and exercise: rats receiving both 5FU/OX and exercise had improved
      cognition relative to non-exercising 5FU/OX rats on novel object recognition and
      spatial reference memory. CONCLUSIONS: The combination 5FU/OX had a significant
      impact on cognition. However, rats treated with 5FU/OX that exercised post
      chemotherapy had improved cognition relative to non-exercising rats. This
      suggests that physical activity may prove useful in ameliorating the cognitive
      impairments induced by 5FU/OX.

PMID- 21894484
TI  - Dose escalation and dose preference in extended-access heroin self-administration
      in Lewis and Fischer rats.
AB  - RATIONALE: A genetic component may be involved in different stages of the
      progression of drug addiction. Heroin users escalate unit doses and frequency of
      self-administration events over time. Rats that self-administer drugs of abuse
      over extended sessions escalate the amount of drug infused over days. OBJECTIVES:
      Using a recently developed model of extended-access self-administration allowing
      for subject-controlled dose escalation of the unit dose, thus potentially
      escalating the unit dose and number of infusions, we compared for the first time
      two genetically different inbred rat strains, Fischer and Lewis. METHODS:
      Extended (18 h/day) self-administration lasted for 14 days. Rats had access to
      two active levers associated with two different unit doses of heroin. If a rat
      showed preference for the higher unit dose, then the available doses were
      escalated in the following session. Four heroin unit doses were available (20,
      50, 125, 250 MUg/kg per infusion). RESULTS: Fischer rats did not escalate the
      unit dose of heroin self-administered; daily amount of heroin administered
      remained low, with a mean daily intake of 1.27 +/- 0.22 mg/kg per session. In
      marked contrast, Lewis rats escalated the total daily amount of heroin self
      administered from 3.94 +/- 0.82 mg/kg on day 1 to 8.95 +/- 2.2 mg/kg on day 14;
      almost half of the subjects preferred a higher heroin dose than Fischer rats.
      CONCLUSION: These data are consistent with the hypothesis that Lewis rats are
      prone to opiate taking and escalation, and are in agreement with our previous
      data obtained with cocaine.

PMID- 21894485
TI  - Effect of d-amphetamine on post-error slowing in healthy volunteers.
AB  - RATIONALE: Post-error slowing has long been considered a sign of healthy error
      detection and an important component of cognitive function. However, the
      neuropharmacological processes underlying post-error slowing are poorly
      understood. OBJECTIVES: This study investigated the effect of the dopamine
      agonist d-amphetamine on post-error slowing and secondarily, the potential
      mediator of drug-induced euphoria and potential moderators of personality and
      baseline task performance. METHODS: Healthy male and female participants (N =
      110) completed four study sessions, at which d-amphetamine (placebo 5, 10, 20 mg)
      was administered under double-blind, counter-balanced conditions. At each
      session, participants completed subjective drug effect assessments and a working
      memory task (N-back) to measure post-error slowing. They completed the
      Multidimensional Personality Questionnaire (MPQ) during screening. RESULTS:
      Amphetamine (20 mg) reduced post-error slowing, consistent with a dampened
      behavioral reactivity to errors. This was not related to drug-induced euphoria.
      Although higher scores on MPQ constraint were related to less post-error slowing
      under placebo conditions, neither personality nor baseline cognitive performance
      moderated the effects of amphetamine on post-error slowing. CONCLUSIONS: The
      finding that amphetamine reduced post-error slowing supports the idea that
      dopamine plays a role in error stimulus processing. The finding is discussed in
      relation to an existing literature on the mechanisms and function of behavioral
      and electrophysiological indices of error sensitivity.

PMID- 21894486
TI  - Nucleus accumbens and delay discounting in rats: evidence from a new quantitative
      protocol for analysing inter-temporal choice.
AB  - RATIONALE: There is evidence that the core of the nucleus accumbens (AcbC) is
      involved in inter-temporal choice behaviour. OBJECTIVE: A new behavioural
      protocol was used to examine the effect of destruction of the AcbC on delay
      discounting in inter-temporal choice schedules in rats. METHOD: Rats with
      excitotoxic lesions of the AcbC or sham lesions made repeated choices on an
      adjusting-delay schedule between a smaller reinforcer (A) that was delivered
      immediately and a larger reinforcer (B) that was delivered after a delay which
      increased or decreased depending on the subject's choices. In two phases of the
      experiment, reinforcer sizes were selected which enabled theoretical parameters
      expressing delay discounting and sensitivity to reinforcer size to be estimated
      from the ratio of the indifference delays (i.e. the quasi-stable values of the
      adjusting delay seen after extended training) obtained in the two phases.
      RESULTS: In both groups, indifference delays were shorter when the sizes of A and
      B were 14 and 25 MUl than when they were 25 and 100 MUl of a 0.6 M sucrose
      solution. Indifference delays were shorter in AcbC-lesioned than in sham-lesioned
      rats. Estimates of delay discounting rate based on the ratio of the indifference
      delays were lower in the AcbC-lesioned than in the sham-lesioned rats. The size
      sensitivity parameter did not differ between the groups. Adjusting delays in
      successive blocks of trials were analysed using Fourier transform. The period
      corresponding to the dominant frequency of the power spectrum and power within
      the dominant frequency band did not differ between the groups. CONCLUSIONS:
      Destruction of the AcbC increased the rate of delay discounting.

PMID- 21894487
TI  - Nicotine self-administered directly into the VTA by rats is weakly reinforcing
      but has strong reinforcement enhancing properties.
AB  - RATIONALE: Rats will lever press to deliver nanolitre quantities of nicotine or
      the muscarinic agonist carbachol directly into the ventral tegmental area (VTA).
      The purpose of these experiments was to investigate further the characteristics
      of nicotine self-administration directly into the VTA. OBJECTIVES: This study
      aimed to confirm previous data relating to intra-VTA self-administration of
      nicotine and carbachol and then test two hypotheses: (a) that pre-sensitisation
      of nicotinic receptors is needed for robust intra-VTA self administration and (b)
      that rats will lever press for intra-VTA nicotine if pre-trained to associate
      lever pressing with a rewarding outcome. METHODS: Rats were equipped with
      cannulae aimed at posterior VTA and allowed five sessions to self-administer
      nicotine or carbachol. In different experiments, rats were either pre-sensitised
      to nicotine by subcutaneous (s.c.) injections or pre-trained to lever press for
      food and a simultaneous conditioned stimulus light. RESULTS: We confirmed that
      carbachol had strong activating effects when self-administered into the VTA;
      selective responding for nicotine developed over five sessions by reduction in
      the amount of pressing on an inactive lever. Prior sensitisation did not improve
      responding for intra-VTA nicotine but training rats to lever press before putting
      them on the drug regime did potentiate pressing. CONCLUSIONS: The action of
      nicotine in the VTA might be better considered as reinforcement enhancing and
      that its intrinsic rewarding property here is at best weak. Identification of the
      VTA as a target for the reinforcement enhancing effects of nicotine is compatible
      with the reinforcement-related functions of VTA dopamine neurons and their
      cholinergic inputs.

PMID- 21894488
TI  - Conditioning domestic chickens to a magnetic anomaly.
AB  - Young domestic chicks of two strains, ISA brown layers and White Leghorn X
      Australorps, were trained to associate a magnetic anomaly with food. This was
      done by feeding them in their housing boxes from a dish placed above a small coil
      that produced a magnetic anomaly roughly six times as strong as the local
      geomagnetic field. Unrewarded tests began on day 9 after hatching. In a square
      arena, two corresponding coils were placed underneath two opposite corners. One
      coil, the control coil, was double-wrapped producing no net magnetic field, while
      the other in the opposite corner produced a local magnetic anomaly similar to
      that experienced during feeding. The chicks favoured the corner with the anomaly
      from day 10 after hatching onward. Both strains of chickens showed this
      preference, indicating that they could sense the local changes in the magnetic
      field.

PMID- 21894489
TI  - Capabilities and quality of life in Dutch psycho-geriatric nursing homes: an
      exploratory study using a proxy version of the ICECAP-O.
AB  - PURPOSE: To validate the ICECAP-O capability measure in psycho-geriatric elderly
      in nursing homes, we compared the capability scores of restrained and
      unrestrained clients. Both nursing staff and family were used as proxies for
      assessing clients' capabilities. METHOD: For 122 psycho-geriatric elderly, a
      total of 96 nursing professionals and 68 family members completed a proxy
      questionnaire. We investigated the convergent and discriminant validity of the
      ICECAP-O and measures of care dependency, health-related quality of life, and
      overall quality of life. We also directly compared ICECAP-O scores of the 56
      clients for whom both nursing staff and family members had completed the
      questionnaire. RESULTS: Convergent validity between ICECAP-O and care dependency,
      health-related, and overall quality of life measures could be established, as
      well as discriminant validity for the restrained and unrestrained groups. Nursing
      and family proxy ICECAP-O tariffs were not significantly correlated. DISCUSSION:
      ICECAP-O measures a more general concept than health-related quality of life and
      can differentiate between restrained and non-restrained psycho-geriatric clients.
      Since nurses seem to be able to assess the current quality of life of clients
      using the ICECAP-O more precisely than the family proxies, for now the use of
      nursing proxies is recommended in a nursing home setting.

PMID- 21894490
TI  - Cancer survivorship practices, services, and delivery: a report from the
      Children's Oncology Group (COG) nursing discipline, adolescent/young adult, and
      late effects committees.
AB  - PURPOSE: To describe survivorship services provided by the Children's Oncology
      Group (COG), an assessment of services was undertaken. Our overall aims were (1)
      to describe survivorship services, including the extent of services provided,
      resources (personnel, philanthropy, and research funding), billing practices, and
      barriers to care and 2) to describe models of care that are in use for childhood
      cancer survivors and adult survivors of childhood cancer. METHODS: One hundred
      seventy-nine of 220 COG institutions (81%) completed an Internet survey in 2007.
      RESULTS: One hundred fifty-five (87%) reported providing survivorship care. Fifty
      nine percent of institutions provide care for their pediatric population in
      specialized late effects programs. For adult survivors, 47% of institutions chose
      models of care, which included transitioning to adult providers for risk-based
      health care, while 44% of institutions keep survivors indefinitely at the
      treating institution (Cancer Center Based Model without Community Referral).
      Sixty-eight percent provide survivors with a copy of their survivorship care
      plan. Only 31% of institutions provide a detailed summary of results after each
      clinic visit, and 41% have a database to track survivor health outcomes. Minimal
      time required for initial and annual survivorship visits is estimated to be
      approximately 120 and 90 min, respectively. The most prevalent barriers to care
      were the lack of dedicated time for program development and a perceived
      insufficient knowledge on the part of the clinician receiving the transition
      referral. CONCLUSIONS: Not all COG institutions provide dedicated survivorship
      care, care plans, or have databases for tracking outcomes. Transitioning to adult
      providers is occurring within the COG. Survivorship care is time intensive.

PMID- 21894491
TI  - Archaea-based microbial fuel cell operating at high ionic strength conditions.
AB  - In this work, two archaea microorganisms (Haloferax volcanii and Natrialba
      magadii) used as biocatalyst at a microbial fuel cell (MFC) anode were evaluated.
      Both archaea are able to grow at high salt concentrations. By increasing the
      media conductivity, the internal resistance was diminished, improving the MFC's
      performance. Without any added redox mediator, maximum power (P (max)) and
      current at P (max) were 11.87/4.57/0.12 MUW cm(-2) and 49.67/22.03/0.59 MUA cm(
      2) for H. volcanii, N. magadii and E. coli, respectively. When neutral red was
      used as the redox mediator, P (max) was 50.98 and 5.39 MUW cm(-2) for H. volcanii
      and N. magadii, respectively. In this paper, an archaea MFC is described and
      compared with other MFC systems; the high salt concentration assayed here,
      comparable with that used in Pt-catalyzed alkaline hydrogen fuel cells, will open
      new options when MFC scaling up is the objective necessary for practical
      applications.

PMID- 21894492
TI  - Health perception and health behaviors of elder Tibetans living in India and
      Switzerland.
AB  - Tibetan elders have lived in exile since the failed uprising against Chinese rule
      in 1959. Using mixed methods approach, this study explored the perceived health
      and health behaviors of 30 older Tibetans living in India and Switzerland using
      Bronfenbrenner's Ecological Systems Model. Results indicate that elder Tibetans
      living in Switzerland enjoyed better health and well-being than those living in
      India. Because of the availability of old age benefits, pensions, and health
      insurance, participants in Switzerland had greater financial independence, and
      fewer problems with healthcare access and affordability than those in India. In
      addition to financial reimbursement, the contribution and importance of personal,
      familial, community, and religious factors to participant's health behaviors are
      examined. The study is a case example depicting the impact of different factors
      from micro to macro on the health and well-being of a refugee group. Its
      implications such as the implementation of old age benefits for older persons
      living in developing countries are discussed.

PMID- 21894493
TI  - Radiotherapy strategies for recurrent and metastatic breast cancer.

PMID- 21894494
TI  - Label-free spatial analysis of free and enzyme-bound NAD(P)H in the presence of
      high concentrations of melanin.
AB  - The analysis of autofluorescence, often regarded as undesired noise during the
      imaging of biological samples, allows label free, unbiased detection of NAD(P)H
      and melanin in native samples. Because both the emission and absorption spectra
      of these fluorophores overlap and they can hence not be differentiated using
      emission filters or with different excitation wavelengths, fluorescence lifetime
      imaging microscopy (FLIM) is used to differentiate between them. In the present
      paper the application of two-photon excitation microscopy is presented to
      investigate the autofluorescence of fungal spores. The model organism which was
      examined is Aspergillus ochraceus. Furthermore a strategy is developed which
      allows to quantitatively analyze the fluorescence lifetimes of melanin, free
      NAD(P)H and protein-bound NAD(P)H using forward convolution of a multiexponential
      decay function with the instrument response function (IRF) and subsequent fitting
      to the experimental fluorescence data. As a consequence proteins, which are able
      to bind NAD(P)H, are located with sub-cellular resolution. Furthermore a spatial
      differentiation of the fluorophores NAD(P)H and melanin inside the spores, is
      revealed.

PMID- 21894495
TI  - A pilot study of the water quality of the Yarra River, Victoria, Australia, using
      in vitro techniques.
AB  - A pilot study was initiated to provide the first information on the recombinant
      receptor-reporter gene bioassay (hormonal) activity of freshwaters in Victoria.
      The project involved the collection of water samples from six stations on the
      main stem of the Yarra River in and upstream of the city of Melbourne, Australia
      in April 2008 and April 2009. Samples were prepared for measurement of sample
      toxicity using a modified photobacterium test, genotoxicity using a high
      throughput luminescent umu test method, and human and medaka estrogen receptor
      (hERalpha and medERalpha), retinoic acid receptor (RAR), aryl hydrocarbon
      receptor (AhR) and thyroid receptor (TR) assay activity using the relevant yeast
      based bioassays. Most samples were only weakly or moderately toxic, with no
      relationship observed to location along the river. The data for 2008 suggests
      that at that time the Yarra River samples contained few compounds that were, in
      and of themselves, genotoxic. No estrogenic or thyroid, and <1 ng/L retinoic acid
      receptor activity was observed. AhR activity increased with progressed
      downstream. AhR activity was higher in April 2009 than at the same time in 2008,
      perhaps as a result of extensive bush fires in the catchment in the months
      immediately prior to sampling. About 24% of the total AhR activity observed was
      associated with suspended solids.

PMID- 21894496
TI  - Enhanced analysis of intracerebral arterioveneous malformations by the
      intraoperative use of analytical indocyanine green videoangiography: technical
      note.
AB  - In cerebral arterioveneous malformations (AVMs) detailed intraoperative
      identification of feeding arteries, nidal vessels and draining veins is crucial
      for surgery. Intraoperative imaging techniques like indocyanine green
      videoangiography (ICG-VAG) provide information about vessel architecture and
      patency, but do not allow time-dependent analysis of intravascular blood flow.
      Here we report on our first experiences with analytical indocyanine green
      videoangiography (aICG-VAG) using FLOW 800 software as a useful tool for
      assessing the time-dependent intraoperative blood flow during surgical removal of
      cerebral AVMs. Microsope-integrated colour-encoded aICG-VAG was used for the
      surgical treatment of a 38-year-old woman diagnosed with an incidental AVM,
      Spetzler Martin grade I, of the left frontal lobe and of a 26-year-old man
      suffering from seizures caused by a symptomatic AVM, Spetzler Martin grade III,
      of the right temporal lobe. Analytical ICG-VAG visualization was intraoperatively
      correlated with in situ micro-Doppler investigation, as well as preoperative and
      postoperative digital subtraction angiography (DSA). Analytical ICG-VAG is fast,
      easy to handle and integrates intuitively into surgical procedures. It allows
      colour-encoded visualization of blood flow distribution with high temporal and
      spatial resolution. Superficial major and minor feeding arteries can be clearly
      separated from the nidus and draining veins. Effects of stepwise vessel
      obliteration on velocity and direction of AVM blood flow can be objectified. High
      quality of visualization, however, is limited to the site of surgery. Colour
      encoded aICG-VAG with FLOW 800 enables intraoperative real-time analysis of
      arterial and venous vessel architecture and might, therefore, increase efficacy
      and safety of neurovascular surgery in a selected subset of superficial AVMs.

PMID- 21894498
TI  - Craniopharyngiomas involving the floor of the third ventricle.

PMID- 21894499
TI  - Elastofibroma oralis.

PMID- 21894500
TI  - Phase II study of oral S-1 with irinotecan and bevacizumab (SIRB) as first-line
      therapy for patients with metastatic colorectal cancer.
AB  - Fluorouracil (5-FU) plus irinotecan combined with bevacizumab has significant
      activity in metastatic colorectal cancer (mCRC), but S-1 has become a substitute
      for continuous infusion of 5-FU and has a very low incidence of hand-foot
      syndrome. With the S-1 plus irinotecan regimen (SIR), the response rate was
      62.5%, and the progression-free survival was 8.0 months. We report here on an
      update of efficacy and safety of the SIR plus bevacizumab (SIRB) regimen as first
      line treatment for mCRC patients. Fifty-one eligible patients with histologically
      confirmed advanced or recurrent colorectal cancer received this treatment. S-1
      was administered orally on days 1-14 of a 21-day cycle. Patients were assigned on
      the basis of body surface area (BSA) to receive one of the following oral doses
      twice daily: 40 mg, 50 mg, or 60 mg. Irinotecan (150 mg/m(2)) plus bevacizumab
      (7.5 mg/kg) were administered by intravenous infusion on day 1. Safety analysis
      identified a grade 3/4 neutropenia rate of 26%. Other grade 3/4 toxicities were
      diarrhea (8%), nausea (6%), vomiting (2%), and hypertension (8%). The response
      rate was 67% and the median progression-free survival time was 373 days. The SIRB
      regimen appears to be highly active and well tolerated as first-line treatment
      for mCRC.

PMID- 21894501
TI  - An investigation into the influence of socioeconomic variables on gestational
      body mass index in pregnant women living in a peri-urban settlement, South
      Africa.
AB  - Maternal and child mortality rates are still unacceptably high in South Africa.
      The health status of women in peri-urban areas has been influenced by political
      and socio-economic factors. Examining socio-economic variables (SEV) in a
      population aids in the explanation of the impact of social structures on an
      individual. Risk factors can then be established and pregnant women in these
      higher risk groups can be identified and given additional support during
      pregnancy. The aim of this study was to investigate the association between SEV
      and gestational Body Mass Index (GBMI) in a peri-urban settlement, South Africa.
      This was a sub-study of the Philani Mentor Mothers' Study (2009-2010). Maternal
      anthropometry and SEV were obtained from 1,145 participants. Multinomial
      regression was used to analyse the data. Household income was the only SEV that
      was significantly associated with GBMI. The odds of being underweight rather than
      normal weight during pregnancy increase by a factor of 2.145 (P < 0.05) for those
      who had a household income lower than R2000 per month. All other SEV were not
      significant. Logistic regression was therefore not carried out. Women who had a
      lower income were at risk of having a lower GBMI during pregnancy. This can lead
      to adverse birth outcomes such as premature birth, low birth weight, height and
      head circumference. Public health policy needs to be developed to include optimal
      nutrition health promotion strategies targeting women with a low income ante and
      post-natally. Once implemented, they need to be evaluated to assess the impact on
      maternal and child mortality.

PMID- 21894502
TI  - The impact of three strains of oral bacteria on the surface and mechanical
      properties of a dental resin material.
AB  - The purpose of this study was to determine if three strains of bacteria could
      impact the mechanical or surface properties of a dental resin material. Resin
      material specimens were incubated at 37 degrees C in sterile saline, tryptic soy
      broth supplemented with sucrose (TSBS), or TSBS inoculated with Streptococcus
      mutans, Streptococcus gordonii, or Streptococcus sanguis. The specimens were
      subjected to Fourier transform infrared spectroscopy before and after incubation.
      The flexural strength test was performed once a week for 6 weeks. Microhardness
      and scanning electron microscopy (SEM) was performed on specimens at 1 and 6
      weeks. Differences in the area under the carbonyl peak were statistically
      significant for the specimens incubated in the media inoculated with either S.
      mutans or S. gordonii. To determine why S. sanguis did not produce changes as the
      other bacteria did, triethylene glycol dimethacrylate, methacrylic acid, and
      triethylene glycol were added to bacterial cultures at increasing concentrations.
      Both methacrylic acid and triethylene glycol reduced the number of colony-forming
      units of S. sanguis. Specimens incubated in TSBS, saline or in culture with S.
      sanguis demonstrated a decrease in peak stress in week 1 of the flexure strength
      test. SEM demonstrated that surface topology changed for those specimens
      incubated in culture with S. mutans or S. gordonii. The changes in surface
      topology demonstrated here could contribute to the secondary caries and changes
      in esthetic properties seen clinically with the use of resin materials in dental
      restorations.

PMID- 21894503
TI  - Thermodynamic stability and energetics of DNA duplexes containing major
      intrastrand cross-links of second-generation antitumor dinuclear Pt(II)
      complexes.
AB  - The effects of major DNA intrastrand cross-links of antitumor dinuclear Pt(II)
      complexes [{trans-PtCl(NH(3))(2)}(2)-MU-{trans
      (H(2)N(CH(2))(6)NH(2)(CH(2))(2)NH(2)(CH(2))(6)NH(2))}](4+) (1) and
      [{PtCl(DACH)}(2)-MU-{H(2)N(CH(2))(6)NH(2)(CH(2))(2)NH(2)(CH(2))(6)NH(2))}](4+)
      (2) (DACH is 1,2-diaminocyclohexane) on DNA stability were studied with emphasis
      on thermodynamic origins of that stability. Oligodeoxyribonucleotide duplexes
      containing the single 1,2, 1,3, or 1,5 intrastrand cross-links at guanine
      residues in the central TGGT, TGTGT, or TGTTTGT sequences, respectively, were
      prepared and analyzed by differential scanning calorimetry. The unfolding of the
      platinated duplexes was accompanied by unfavorable free energy terms. The
      efficiency of the cross-links to thermodynamically destabilize the duplex
      depended on the number of base pairs separating the platinated bases. The trend
      was 1,5->1,2->1,3 cross-link of 1 and 1,5->1,3->1,2 cross-link of 2.
      Interestingly, the results showed that the capability of the cross-links to
      reduce the thermodynamic stability of DNA (DeltaG(298)(0)) correlated with the
      extent of conformational distortions induced in DNA by various types of
      intrastrand cross-links of 1 or 2 determined by chemical probes of DNA
      conformation. We also examined the efficiency of the mammalian nucleotide
      excision repair systems to remove from DNA the intrastrand cross-links of 1 or 2.
      The efficiency of the excinucleases to remove the cross-links from DNA depended
      on the length of the cross-link; the trend was identical to that observed for the
      efficiency of the intrastrand cross-links to thermodynamically destabilize the
      duplex. Thus, the results are consistent with the thesis that an important factor
      that determines the susceptibility of the intrastrand cross-links of dinuclear
      platinum complexes 1 and 2 to be removed from DNA by nucleotide excision repair
      is the efficiency of these lesions to thermodynamically destabilize DNA.

PMID- 21894505
TI  - Groundwater quality assessment based on rough sets attribute reduction and TOPSIS
      method in a semi-arid area, China.
AB  - In order to enrich and improve the groundwater quality assessment system, a new
      coupled assessment model based on rough set attribute reduction and the technique
      for order preference by similarity to ideal solution (TOPSIS) was proposed. The
      proposed model was applied in the groundwater quality assessment of a semi-arid
      area, northwest China. The results show that most chemical indices except NH (4)
      (+) , F(-), and Mn meet the Standards for Drinking Water of China and the
      groundwater quality overall is good. All assessed water samples are found to be
      fit for human consumption according to the comprehensive assessment results.
      Rough set attribute reduction for groundwater quality assessment is practical.
      The assessment results after attribute reduction show a good consistency with
      those before attribute reduction. Rough set attribute reduction and TOPSIS
      evaluation coupled model is clear in ideas and simple in calculation, and
      evaluation results are reasonable as well. The coupled model can be applied to
      solve many multiple criteria decision making problems such as groundwater quality
      assessment.

PMID- 21894504
TI  - Evidence for pH-dependent multiple conformers in iron(II) heme-human serum
      albumin: spectroscopic and kinetic investigation of carbon monoxide binding.
AB  - Human serum albumin (HSA), the most prominent protein in plasma, is best known
      for its exceptional ligand binding capacity. HSA participates in heme scavenging
      by binding the macrocycle at fatty acid site 1. In turn, heme endows HSA with
      globin-like reactivity and spectroscopic properties. A detailed pH-dependent
      kinetic and spectroscopic investigation of iron(II) heme-HSA and of its
      carbonylated form is reported here. Iron (II) heme-HSA is a mixture of a four
      coordinate intermediate-spin species (predominant at pH 5.8 and 7.0), a five
      coordinate high-spin form (mainly at pH 7.0), and a six-coordinate low-spin
      species (predominant at pH 10.0). The acidic-to-alkaline reversible transition
      reflects conformational changes leading to the coordination of the heme Fe(II)
      atom by the His146 residue via its nitrogen atom, both in the presence and in the
      absence of CO. The presence of several species accounts for the complex,
      multiexponential kinetics observed and reflects the very slow interconversion
      between the different species observed both for CO association to the free
      iron(II) heme-HSA and for CO dissociation from CO-iron(II) heme-HSA as a function
      of pH.

PMID- 21894506
TI  - Columnar aerosol optical and radiative properties according to season and air
      mass transport pattern over East Asia.
AB  - The column-integrated optical and radiative properties of aerosols in the
      downwind area of East Asia were investigated based on sun/sky radiometer
      measurements performed from February 2004 to June 2005 at Gwangju (35.23 degrees 
      N, 126.84 degrees  E) and Anmyeon (36.54 degrees  N, 126.33 degrees  E), Korea.
      The observed aerosol data were analyzed for differences among three seasons:
      spring (March-May), summer (June-August), and autumn/winter (September-February).
      The data were also categorized into five types depending on the air mass origin
      in arriving in the measurement sites: (a) from a northerly direction in spring
      (S(N)), (b) from a westerly direction in spring (S(W)), (c) cases with a low
      Angstrom exponent (<0.8) in spring (dust), (d) from a northerly direction in
      autumn/winter (AW(N)), and (e) from a westerly direction during other seasons
      (AW(W)). The highest Angstrom exponents (alpha) at Gwangju and Anmyeon were 1.43
      +/- 0.30 and 1.49 +/- 0.20, respectively, observed in summer. The lowest column
      mean single-scattering albedo (omega) at 440 nm observed at Gwangju and Anmyeon
      were 0.89 +/- 0.02 and 0.88 +/- 0.02, respectively, during a period marked by the
      advection of dust from the Asian continent. The highest omega values at Gwangju
      and Anmyeon were 0.95 +/- 0.02 and 0.96 +/- 0.02, respectively, observed in
      summer. Variations in the aerosol radiative-forcing efficiency (beta) were
      related to the conditions of the air mass origin. The forcing efficiency in
      summer was -131.7 and -125.6 W m(-2) at the surface in Gwangju and Anmyeon,
      respectively. These values are lower than those under the atmospheric conditions
      of spring and autumn/winter. The highest forcing efficiencies in autumn/winter
      were -214.3 and -255.9 W m(-2) at the surface in Gwangju and Anmyeon,
      respectively, when the air mass was transported from westerly directions.

PMID- 21894507
TI  - Determining storm sampling requirements for improving precision of annual load
      estimates of nutrients from a small forested watershed.
AB  - This study sought to determine the lowest number of storm events required for
      adequate estimation of annual nutrient loads from a forested watershed using the
      regression equation between cumulative load (?L) and cumulative stream discharge
      (?Q). Hydrological surveys were conducted for 4 years, and stream water was
      sampled sequentially at 15-60-min intervals during 24 h in 20 events, as well as
      weekly in a small forested watershed. The bootstrap sampling technique was used
      to determine the regression (?L-?Q) equations of dissolved nitrogen (DN) and
      phosphorus (DP), particulate nitrogen (PN) and phosphorus (PP), dissolved
      inorganic nitrogen (DIN), and suspended solid (SS) for each dataset of ?L and ?Q.
      For dissolved nutrients (DN, DP, DIN), the coefficient of variance (CV) in 100
      replicates of 4-year average annual load estimates was below 20% with datasets
      composed of five storm events. For particulate nutrients (PN, PP, SS), the CV
      exceeded 20%, even with datasets composed of more than ten storm events. The
      differences in the number of storm events required for precise load estimates
      between dissolved and particulate nutrients were attributed to the goodness of
      fit of the ?L-?Q equations. Bootstrap simulation based on flow-stratified
      sampling resulted in fewer storm events than the simulation based on random
      sampling and showed that only three storm events were required to give a CV below
      20% for dissolved nutrients. These results indicate that a sampling design
      considering discharge levels reduces the frequency of laborious chemical analyses
      of water samples required throughout the year.

PMID- 21894508
TI  - Solid focal liver lesions indeterminate by contrast-enhanced CT or MR imaging:
      the added diagnostic value of contrast-enhanced ultrasound.
AB  - The main clinically recognized application of contrast-enhanced US (CEUS) with
      microbubble contrast agents is the characterization of incidental focal liver
      lesions. CEUS with low transmit power insonation allows the real-time assessment
      of contrast enhancement in a focal liver lesion after microbubble contrast agent
      injection, during the arterial (10-25 s), portal venous (from 35 s up to 2 min)
      and late phase (4-6 min after microbubble injection). During the portal venous
      and late phase benign lesions appear hyper or iso-enhancing in comparison to the
      adjacent liver parenchyma, while malignant lesions prevalently present contrast
      washout with hypo-enhancing appearance. CEUS may provide an added diagnostic
      value in those incidental focal liver lesions in which contrast-enhanced CT or MR
      imaging are not conclusive. In particular, CEUS may provide an added diagnostic
      value in those focal liver lesions appearing indeterminate on single-phase CT
      scan, or on CT scans performed by an incorrect delay time or also after injection
      of a low dose of iodinated contrast agent, or also in those focal liver lesions
      revealing equivocal enhancement patterns on contrast-enhanced CT or MR imaging.
      CEUS may have an added diagnostic value also in hepatocellular nodules in a
      cirrhotic liver and can be considered a complementary imaging technique to CT.

PMID- 21894509
TI  - Intrinsic susceptibility of Giardia duodenalis assemblage subtypes A(I), A(II), B
      and E(III) for nitric oxide under axenic culture conditions.
AB  - The antigiardial effects of nitric oxide (NO.) have been reported in vitro, but
      only for assemblage A(I) lab strains. This study investigated the intrinsic NO.
      susceptibility of different assemblage subtypes. The susceptibility (IC50) for
      NO. released by MAHMA NONOate was studied for three lab (WB, G1 and GS/M-83-H7)
      and six field isolates of assemblage subtypes A(I), A(II), B and E(III). Tests
      were performed in phosphate-buffered saline supplemented with L-cysteine HCl,
      trypticase peptone, powder bovine bile and 20% inactivated foetal calf serum (for
      assemblages A and E) or human serum (for assemblage B), adjusted to pH 7.3, to
      support adequate trophozoite survival. Flow cytometry with fluorescein diacetate
      and propidium iodide as viability indicators was used to determine trophozoite
      viability. This study indicated that the NO. susceptibilities of assemblage A lab
      and field strains (subtypes A(I) and A(II)) were fully comparable, indicating
      that the NO. susceptibility of the lab strains remained representative for their
      genotype. The trophozoites of assemblages B and E(III) showed comparable NO.
      susceptibilities that were markedly higher than the susceptibilities of
      assemblage subtypes A(I) and A(II). This study suggests a role for the assemblage
      subtype in defining NO. susceptibilities. The underlying mechanisms still need to
      be elucidated, but assemblage-linked differences in the expression of the genes
      coding for flavohemoglobin or A-type flavoprotein may certainly deserve further
      attention.

PMID- 21894510
TI  - Early intrauterine embryonic development in Khawia sinensis Hsu, 1935 (Cestoda,
      Caryophyllidea, Lytocestidae), an invasive tapeworm of carp (Cyprinus carpio): an
      ultrastructural study.
AB  - Intrauterine embryonic development in the caryophyllidean tapeworm Khawia
      sinensis has been investigated using transmission electron microscopy and
      cytochemical staining with periodic acid-thiosemicarbazide-silver proteinate for
      glycogen. Contrary to previous light microscopy findings that reported the
      release of non-embryonated eggs of K. sinenesis to the external environment, the
      present study documents various stages of embryonation (ovoviviparity) within the
      intrauterine eggs of this cestode. At the initial stage of embryonic development,
      each fertilised oocyte is accompanied by several vitellocytes that become
      enclosed within the operculate, electrondense shell. Cleavage divisions result in
      formation of blastomeres (up to about 24 cells) of various sizes. Mitotic
      divisions and apparent rosette arrangment of the blastomeres, the latter atypical
      within the Eucestoda, are observed for the first time in the intrauterine eggs of
      K. sinenesis. The early embryo enclosed within the electrondense shell is
      surrounded by a thin membraneous layer which in some enlarged regions shows
      presence of nuclei. Simultaneously to multiplication and differentiation, some of
      the blastomeres undergo deterioration. A progressive degeneration of the
      vitellocytes within eggs provides nutritive reserves, including lipids, for the
      developing embryo. The possible significance of this atypical timing of the
      intrauterine embryonic development to (1) the ecology of K. sinensis and that of
      a recent introduction of another invasive tapeworm, the caryophyllidean
      Atractolytocestus huronensis Anthony, 1958 to Europe; and (2) the affiliation of
      caryophyllideans with other lower cestodes, are discussed.

PMID- 21894511
TI  - Does sleep differ among patients with common musculoskeletal pain disorders?
AB  - Most patients with chronic musculoskeletal pain report poor-quality sleep. The
      impact of chronic pain on sleep can be described as a vicious circle with mutual
      deleterious influences between pain and sleep-associated symptoms. It is
      difficult, however, to extract quantitative or consistent and specific sleep
      variables (eg, total sleep time, slow-wave sleep, sleep stage duration) that
      characterize the pain-related disruption of sleep. Comorbidity (eg, fatigue;
      depression; anxiety, sleep, movement, or breathing disorders) often confounds the
      reading and interpretation of sleep traces. Furthermore, many other methodologic
      issues complicate our ability to generalize findings (low external validity) to
      first-line medicine. Because sleep alterations in common musculoskeletal pain are
      neither specific nor pathognomonic, the aim is to provide a critical overview of
      the current understanding of pain and sleep interaction, discussing evidence
      based and empiric knowledge that should be considered in further research and
      clinical applications.

PMID- 21894512
TI  - Treatment of intracranial aneurysms. Reconstruction of the parent artery with
      flow-diverting (Silk) stent.
AB  - INTRODUCTION: Since the flow diverters (FDs) have been introduced it is possible
      to treat aneurysms that are considered difficult or impossible to treat with
      usual endovascular or surgical methods. It is still uncertain which aneurysms are
      suitable for this new treatment. We present the periprocedural complications,
      immediate result, late complications, imaging follow-up at 6 and 12 months and
      clinical follow-up at 2-23 months. METHODS: Twenty-two patients with 26 wide
      necked or blister-like aneurysms had 23 treatments with implantation of a Silk
      stent. Eleven patients had re-canalizations, and 11 patients were either
      untreated or had been treated for another aneurysm. RESULTS: Periprocedural
      complications were seen in four treatments (17%). However, none of these had
      clinical consequences. Mortality and morbidity rates were 1 of 22 (5%) and 1 of
      22 (5%), respectively. Clinical outcome was unchanged in 16 patients (72%), 3
      patients improved (14%) and 3 patients worsened (14%). The end-of-procedure
      angiography did not show complete occlusion of any of the aneurysms, but at 6
      months follow-up angiography, 17 of 25 aneurysms (68%) were completely occluded,
      and at 12 months, 18 of 21 aneurysms (86%) were occluded. CONCLUSION: The effect
      of the Silk FD in terms of occlusion of the aneurysms seems to occur mainly
      during the first 6 months after placement but continues during the following
      time. Most delayed complications occur immediately after discontinuing the
      anticoagulation medication. Considering the complexity of the aneurysms treated,
      the rate of complications is acceptable.

PMID- 21894513
TI  - Fine-needle aspiration cytology of salivary gland tumours: a 10-year
      retrospective analysis.
AB  - INTRODUCTION: The aim of this study was to evaluate the sensitivity, specificity,
      diagnostic accuracy, positive predictive value (PPV) and negative predictive
      value (NPV) of fine-needle aspiration cytology (FNAC) of salivary gland tumours
      performed at a tertiary cancer hospital over a time period of 10 years. MATERIALS
      AND METHODS: A retrospective analysis was carried out between 1995 and 2004 to
      review the cases of patients with salivary gland tumours who had undergone pre
      operative FNA and for whom definite histology was either by tru-cut biopsy or by
      histopathological examination of the operative specimen. RESULTS: A total of 107
      cases of salivary gland tumours were treated during that period, but only 82
      cases diagnosed by FNAC could be correlated with histological and clinical data
      and were considered for this study. The sensitivity, specificity, diagnostic
      accuracy, PPV and NPV were estimated considering 54 benign and 28 malignant
      cases. Sensitivity was 90% (28/31), specificity was 98% (54/55), diagnostic
      accuracy was 95.1% (82/86), PPV was 96% and NPV was 94%. DISCUSSION: This study
      confirms that FNA cytology is a technique that offers high sensitivity,
      specificity and diagnostic accuracy in salivary gland tumour diagnosis.

PMID- 21894514
TI  - Non-alcoholic fatty liver disease and cardiovascular risk: metabolic aspects and
      novel treatments.
AB  - Non-alcoholic fatty liver disease (NAFLD) is usually a silent disease that occurs
      in a very high proportion of people with features of the metabolic syndrome,
      including overweight, insulin resistance and type 2 diabetes. Because obesity and
      type 2 diabetes are now extremely common in Westernised societies, it is likely
      that the prevalence of NAFLD increases markedly in the future. Although
      previously it was thought that NAFLD was harmless, it is now recognised that
      NAFLD can be a progressive liver condition that increases risk of cirrhosis, end
      stage liver disease and hepatocellular carcinoma. Additionally, liver fat
      accumulation causes insulin resistance and increases risk of type 2 diabetes.
      Increasing evidence now shows NAFLD is a risk factor for cardiovascular disease
      (CVD). The purpose of this review is to briefly discuss the pathogenesis of
      NAFLD, to describe the relationship between NAFLD and CVD and the mechanisms
      linking both conditions and to discuss some of the treatment options (including
      lifestyle, nutrition and drugs) that may influence both NAFLD and risk of CVD.

PMID- 21894516
TI  - Two parthenogenetic populations of Chara canescens differ in their capacity to
      acclimate to irradiance and salinity.
AB  - The parthenogens of Chara canescens (Charophyceae) occupy broader geographical
      and ecological ranges than their sexual counterparts. Two possible hypotheses
      explain the ubiquity of parthenogens: the occurrence of one or several
      parthenogens with wide niches, or of many parthenogens that are restricted to
      narrow ecological niches. For the purposes of this study, C. canescens
      individuals from two neighbouring populations of the Baltic Sea (Bodstedter
      Bodden = BB; Salzhaff = SH), which differed significantly in water transparency
      and salinity, were investigated for significant differences in physiological
      capacity. Individuals of both habitats acclimated quickly to daily changes in
      irradiances in the field, but the photosynthetic efficiency of PS II showed a
      significant decrease with increasing daily irradiance in the habitat BB, which
      has lower levels of salinity and water transparency. In addition to the field
      study, individuals were reared under different levels of environmental factors in
      the laboratory: four irradiances (70-600 MUmol m(-2) s(-1)) and five salinity
      levels (0-24 psu). The individuals of both habitats grew almost equally well at
      intermediate salinity levels. Growth under the artificial light supply was
      highest at levels corresponding to the in situ conditions for each population.
      Total chlorophyll was highest at intermediate salinities (BB), or hardly changed
      with salinity (SH). The physiological capacity for individuals from SH clearly
      depends upon changing growth irradiance, whereas the capacity for individuals
      from BB was relatively independent of salinity and irradiance. These findings
      indicate that both parthenogenetic C. canescens populations are locally adapted
      to light. However, to test adaptive potential of the parthenogens, more than two
      populations should be tested in future.

PMID- 21894515
TI  - Expression of galanin and galanin receptor mRNA in skin during the formation of
      granulation tissue.
AB  - Galanin is a neuropeptide widely distributed in the central and peripheral
      nervous systems. Although its role in non-neural cells is poorly understood, it
      is known that during inflammation, the dermis layer of the skin produces and
      releases galanin. The aim of this report is to study the expression of galanin in
      granulation tissue. After inducing inflammation by cotton thread implantation,
      galanin-like immunoreactivity (galanin-LI) in plasma reached a maximum on the
      third day. Galanin-LI was observed in fibroblast-like cells occurring close to
      collagen fibers in developing granulation tissue. Furthermore, galanin receptor
      subtypes 1 and 2 (GALR1 and GALR2)-expressing cells were observed around
      microvessels and were found to produce desmin. Galanin was injected along the
      cotton threads immediately after implantation, resulting in rapid formation of
      granulation tissue, and an increase in the contents of microvessels, indicating a
      stimulatory effect of galanin on the process of angiogenesis in granulation
      tissue. The results demonstrate that some galanin was released from fibroblast
      like cells during the formation of granulation tissue, and that it stimulated
      angiogenesis.

PMID- 21894517
TI  - Trait-based community assembly of understory palms along a soil nutrient gradient
      in a lower montane tropical forest.
AB  - Two opposing niche processes have been shown to shape the relationship between
      ecological traits and species distribution patterns: habitat filtering and
      competitive exclusion. Habitat filtering is expected to select for similar traits
      among coexisting species that share similar habitat conditions, whereas
      competitive exclusion is expected to limit the ecological similarity of
      coexisting species leading to trait differentiation. Here, we explore how
      functional traits vary among 19 understory palm species that differ in their
      distribution across a gradient of soil resource availability in lower montane
      forest in western Panama. We found evidence that habitat filtering influences
      species distribution patterns and shifts community-wide and intraspecific trait
      values. Differences in trait values among sites were more strongly related to
      soil nutrient availability than to variation in light or rainfall. Soil nutrient
      availability explained a significant amount of variation in site mean trait
      values for 4 of 15 functional traits. Site mean values of leaf nitrogen and
      phosphorus increased 37 and 64%, respectively, leaf carbon:nitrogen decreased
      38%, and specific leaf area increased 29% with increasing soil nutrient
      availability. For Geonoma cuneata, the only species occurring at all sites, leaf
      phosphorus increased 34% and nitrogen:phosphorus decreased 42% with increasing
      soil nutrients. In addition to among-site variation, most morphological and leaf
      nutrient traits differed among coexisting species within sites, suggesting these
      traits may be important for niche differentiation. Hence, a combination of
      habitat filtering due to turnover in species composition and intraspecific
      variation along a soil nutrient gradient and site-specific niche differentiation
      among co-occurring species influences understory palm community structure in this
      lower montane forest.

PMID- 21894518
TI  - Genotypes, haplotypes and diplotypes of IGF-II SNPs and their association with
      growth traits in largemouth bass (Micropterus salmoides).
AB  - Insulin-like growth factor II (IGF-II) is involved in the regulation of somatic
      growth and metabolism in many fishes. IGF-II is an important candidate gene for
      growth traits in fishes and its polymorphisms were associated with the growth
      traits. The aim of this study is to screen single nucleotide polymorphisms (SNPs)
      of the largemouth bass (Micropterus salmoides) IGF-II gene and to analyze
      potential association between IGF-II gene polymorphisms and growth traits in
      largemouth bass. Four SNPs (C127T, T1012G, C1836T and C1861T) were detected and
      verified by DNA sequencing in the largemouth bass IGF-II gene. These SNPs were
      found to organize into seven haplotypes, which formed 13 diplotypes (haplotype
      pairs). Association analysis showed that four individual SNPs were not
      significantly associated with growth traits. Significant associations were,
      however, noted between diplotypes and growth traits (P < 0.05). The fish with
      H1H3 (CTCC/CGCC) and H1H5 (CTCC/TTTT) had greater body weight than those with
      H1H1 (CTCC/CTCC), H1H2 (CTCC/TGTT) and H4H4 (TGCT/TGCT/) did. Our data suggest a
      significant association between genetic variations in the largemouth bass IGF-II
      gene and growth traits. IGF-II SNPs could be used as potential genetic markers in
      future breeding programs of largemouth bass.

PMID- 21894519
TI  - Water deficit improved the capacity of arbuscular mycorrhizal fungi (AMF) for
      inducing the accumulation of antioxidant compounds in lettuce leaves.
AB  - Lettuce, a major food crop within the European Union and the most used for the so
      called 'Fourth Range' of vegetables, can associate with arbuscular mycorrhizal
      fungi (AMF). Mycorrhizal symbiosis can stimulate the synthesis of secondary
      metabolites, which may increase plant tolerance to stresses and enhance the
      accumulation of antioxidant compounds potentially beneficial to human health. Our
      objectives were to assess (1) if the application of a commercial formulation of
      AMF benefited growth of lettuce under different types and degrees of water
      deficits; (2) if water restrictions affected the nutritional quality of lettuce;
      and (3) if AMF improved the quality of lettuce when plants grew under reduced
      irrigation. Two cultivars of lettuce consumed as salads, Batavia Rubia Munguia
      and Maravilla de Verano, were used in the study. Four different water regimes
      were applied to both non-mycorrhizal and mycorrhizal plants: optimal irrigation
      (field capacity [FC]), a water regime equivalent to 2/3 of FC, a water regime
      equivalent to 1/2 of FC and a cyclic drought (CD). Results showed that
      mycorrhizal symbiosis improved the accumulation of antioxidant compounds, mainly
      carotenoids and anthocyanins, and to a lesser extent chlorophylls and phenolics,
      in leaves of lettuce. These enhancements were higher under water deficit than
      under optimal irrigation. Moreover, shoot biomass in mycorrhizal lettuces
      subjected to 2/3 of FC were similar to those of non-mycorrhizal plants cultivated
      under well-watered conditions. In addition, lettuces subjected to 2/3 FC had
      similar leaf RWC than their respective well-watered controls, regardless of
      mycorrhizal inoculation. Therefore, results suggest that mycorrhizal symbiosis
      can improve quality of lettuce and may allow restrict irrigation without reducing
      production.

PMID- 21894520
TI  - Cloning of the herpes simplex virus type 1 genome as a novel luciferase-tagged
      infectious bacterial artificial chromosome.
AB  - Herpes simplex virus type 1 (HSV-1) is a ubiquitous human pathogen of skin and
      mucous membranes. In the present study, the genome of the HSV-1 F strain was
      cloned as an infectious bacterial artificial chromosome (BAC) clone without any
      deletions of the viral genes. Additionally, a firefly luciferase cassette was
      inserted to generate a novel luciferase-expressing HSV-1 BAC. Importantly, the
      resulting recombinant HSV-1 BAC Luc behaved indistinguishably from the wild-type
      virus in Vero cells, and the luciferase activity could be easily quantified in
      vitro. Thus, this novel HSV-1 BAC system would serve as a powerful tool for gene
      function profiling.

PMID- 21894521
TI  - Pulmonary function testing in young children.
AB  - Pulmonary function testing (PFT) is of great importance in the evaluation and
      treatment of respiratory diseases. Spirometry is simple, noninvasive, and has
      been the most commonly used technique in cooperative children, obtaining reliable
      data in only a few minutes. The development of commercially available equipment
      as well as the simplification of previous techniques that now require minimal
      patient cooperation applied during tidal breathing have significantly stimulated
      the use of PFT in younger children. Tidal breathing techniques such as impulse
      oscillometry, gas dilution, and plethysmography have permitted previously
      unobtainable PFT in children 2 to 5 years of age. The purpose of this review is
      to help clinicians become familiar with available PFT techniques used in young
      children by discussing their general principles, clinical applications, and
      limitations.

PMID- 21894522
TI  - Sleep disordered breathing in patients with heart failure: pathophysiology and
      management.
AB  - OPINION STATEMENT: Sleep disordered breathing (SDB) is common in heart failure
      patients across the range of ejection fractions and is associated with adverse
      prognosis. Although effective pharmacologic and device-based treatment of heart
      failure may reduce the frequency or severity of SDB, heart failure treatment
      alone may not be adequate to restore normal breathing during sleep. Continuous
      positive airway pressure (CPAP) is the major treatment for SDB in heart failure,
      especially if obstructive rather than central sleep apnea (CSA) predominates.
      Adequate suppression of CSA by PAP is associated with a heart transplant-free
      survival benefit, although randomized trials are ongoing. Bilevel PAP (BPAP) may
      be as effective as CPAP in treating SDB and may be preferable over CPAP in
      patients who experience expiratory pressure discomfort. Adaptive (or auto) servo
      ventilation (ASV), which adjusts the PAP depending on the patient's airflow or
      tidal volume, may be useful in congestive heart failure patients if CPAP is
      ineffective. Other therapies that have been proposed for SDB in congestive heart
      failure include nocturnal oxygen, CO(2) administration (by adding dead space),
      theophylline, and acetazolamide; most of which have not been systematically
      studied in outcome-based prospective randomized trials.

PMID- 21894524
TI  - Purification and properties of a new thermostable cyclodextrin glucanotransferase
      from Bacillus pseudalcaliphilus 8SB.
AB  - A new cyclodextrin glucanotransferase (CGTase, EC 2.4.1.19) from an alkaliphilic
      halotolerant Bacillus pseudalcaliphilus 8SB was studied in respect to its gamma
      cyclizing activity. An efficient conversion of a raw corn starch into only two
      types of cyclodextrins (beta- and gamma-CD) was achieved by the purified enzyme.
      Crude enzyme obtained by ultrafiltration was purified up to fivefold by starch
      adsorption with a recovery of 62% activity. The enzyme was a monomer with a
      molecular mass 71 kDa estimated by sodium dodecyl sulfate polyacrylamide gel
      electrophoresis (SDS-PAGE) and native PAGE. The CGTase exhibited two pH optima,
      at pH 6.0 and 8.0, and was at most active at 60  degrees C and pH 8.0. The enzyme
      retained more than 80% of its initial activity in a wide pH range, from 5.0 to
      11.0. The CGTase was strongly inhibited by 15 mM Cu(2+), Fe(2+), Ag(+), and
      Zn(2+), while some metal ions, such as Ca(2+), Na(+), K(+), and Mo(7+), exerted a
      stimulating effect in concentration of 5 mM. The important feature of the studied
      CGTase was its high thermal stability: the enzyme retained almost 100% of its
      initial activity after 2 h of heating at 40-60  degrees C; its half-life was 2 h
      at 70  degrees C in the presence of 5 mM Ca(2+). The achieved 50.7% conversion of
      raw corn starch into 81.6% beta- and 18.4% gamma-CDs after 24 h enzyme reaction
      at 60  degrees C and pH 8.0 makes B. pseudalcaliphilus 8SB CGTase industrially
      important enzyme for cyclodextrin production.

PMID- 21894523
TI  - Children's depressive symptoms in relation to EEG frontal asymmetry and maternal
      depression.
AB  - This study examined the relations of school-age children's depressive symptoms,
      frontal EEG asymmetry, and maternal history of childhood-onset depression (COD).
      Participants were 73 children, 43 of whom had mothers with COD. Children's EEG
      was recorded at baseline and while watching happy and sad film clips. Depressive
      symptoms were measured using parent-report of Children's Depression Inventory.
      The key findings are the interaction effects between baseline and film frontal
      EEG asymmetry on child depressive symptoms. Specifically, relative right frontal
      EEG asymmetry while watching happy or sad film clip was associated with elevated
      depressive symptoms for children who also exhibited right frontal EEG asymmetry
      at baseline. Results suggest that right frontal EEG asymmetry that is consistent
      across situations may be an marker of depression-prone children.

PMID- 21894525
TI  - Risk of malignancies in IgG4-related disease.
AB  - IgG4-related disease (IgG4-RD) is considered a systemic, chronic, and
      inflammatory disorder that is characterized by the enlargement of involved
      organs, elevated levels of IgG4, and abundant infiltration of plasmacytes with
      IgG4 and fibrosis in involved organs. It is necessary to differentiate IgG4-RD
      from malignant tumors. Recently we have looked at case reports of IgG4-RD with
      malignancy that was discovered at systemic screening. In this study, we analyzed
      the relationship between IgG4-RD and malignancies. The study subjects were 106
      patients with IgG4-RD who had been referred to our hospital since April 1997. We
      analyzed the clinical characteristics of IgG4-RD patients who had cancer that was
      observed upon the initial diagnosis of IgG4-RD or that occurred during an average
      follow-up period of 3.1 years. Using data from national cancer registries that
      monitor cancer incidence in Japan, we evaluated the standardized incidence ratio
      (SIR) for malignancies in IgG4-RD. Malignancies were observed in 11 of the IgG4
      RD patients (10.4%). The malignancies were all different and included lung
      cancer, colon cancer, and lymphoma. With the exception of the age at which the
      IgG4-RD diagnosis was made, there were no common features in patients with cancer
      and those without. The SIR for these malignancies in IgG4-RD was 383.0, which was
      higher than that for the general population. We should be cognizant of the
      possible existence of malignancies in patients with IgG4-RD at the time of
      diagnosis and during follow-up care.

PMID- 21894527
TI  - The scientific rationale for using biomaterials in stress urinary incontinence
      and pelvic organ prolapse.

PMID- 21894526
TI  - Bladder dysfunction in patients with diabetes.
AB  - With diabetes mellitus (DM) reaching epidemic proportions, the identification of
      voiding dysfunction as a common and burdensome complication of this disease is
      critical. Research into diabetic voiding dysfunction significantly lags behind
      other complications of DM, such as retinopathy and nephropathy. Recent studies
      have revealed that DM predisposes patients to a wide range of lower urinary tract
      dysfunction, from the classic diabetic cystopathy of incomplete emptying to
      urgency incontinence. In this review, we discuss the current concepts of diabetic
      voiding dysfunction with a critical analysis of the available evidence.

PMID- 21894529
TI  - Protective immunity provided by a new modified SERA protein peptide: its
      immunogenetic characteristics and correlation with 3D structure.
AB  - The serine repeat antigen (SERA) protein is a leading candidate molecule for
      inclusion as a component in a multi-antigen, multi-stage, minimal subunit-based,
      chemically synthesised anti-malarial vaccine. Peptides having high red blood cell
      binding affinity (known as HABPs) have been identified in this protein. The 6733
      HABP was located in the C-terminal portion of the 47-kDa fragment while HABP 6754
      was located in the C-terminal region of the 56-kDa fragment. These conserved
      HABPs failed to induce an immune response. Critical red blood cell binding
      residues and/or their neighbours (assessed by glycine-analogue scanning) were
      replaced by others having the same mass, volume and surface but different
      polarity, rendering some of them highly immunogenic when assessed by antibody
      production against the parasite or its proteins and protection-inducers against
      experimental challenge with a highly infectious Aotus monkey-adapted Plasmodium
      falciparum strain. This manuscript presents some modified HABPs as vaccine
      candidate components for enriching our tailor-made anti-malarial vaccine
      repertoire, as well as their 3D structure obtained by 1H-NMR displaying a short
      structured region, differently from the native ones having random structures.

PMID- 21894528
TI  - Ligustilide: a novel TRPA1 modulator.
AB  - TRPA1 is activated by electrophilic compounds such as mustard oil (MO). Here, we
      demonstrate a bimodal sensitivity of TRPA1 to ligustilide (Lig), an electrophilic
      volatile dihydrophthalide of dietary and medicinal relevance. Lig is a potent
      TRPA1 activator and is also capable to induce a modest block of MO activated
      currents. Aromatization to dehydroligustilide (DH-Lig), as occurs during aging of
      its botanical sources, reversed this profile, enhancing TRPA1 inhibition and
      reducing activation. Mutation of the reactive cysteines in mouseTRPA1 (C622S,
      C642S, C666S) dramatically reduced activation by MO and significantly reduced
      that by Lig, but had an almost negligible effect on the action of DH-Lig, whose
      activation mechanism of TRPA1 is therefore largely independent from the
      alkylation of cysteine residues. Taken together, these observations show that the
      phthalide structural motif is a versatile platform to investigate the modulation
      of TRPA1 by small molecules, being tunable in terms of activation/inhibition
      profile and mechanism of interaction. Finally, the action of Lig on TRPA1 may
      contribute to the gustatory effects of celery, its major dietary source, and to
      the pharmacological action of important plants from the Chinese and native
      American traditional medicines.

PMID- 21894530
TI  - Correlation between antizyme 1 and differentiation of vascular smooth muscle
      cells cultured in honeycomb-like type-I collagen matrix.
AB  - Vascular smooth muscle cells (SMC) are able to proliferate when cultured on
      plates, but become differentiated when maintained in three-dimensional type I
      collagen matrices (honeycombs). SMC grown in honeycombs contained a low level of
      polyamines due to the presence of antizyme 1 (AZ1), a negative regulator of
      ornithine decarboxylase (ODC) and of polyamine uptake. To clarify the role of AZ1
      in differentiation of SMC in honeycombs, an ODC gene was stably transfected into
      SMC (ODC-SMC). Although proliferation of ODC-SMC on plates was accelerated
      together with an increase in phosphorylated focal adhesion kinase (FAK) and a
      decrease in alpha-actin and myosin, maker proteins of differentiation, growth of
      ODC-SMC ceased in honeycombs similarly to normal SMC with a low level of
      phosphorylated FAK and a high level of alpha-actin and myosin. AZ1 expression in
      ODC-SMC on plates was low, but that in honeycombs was high. Antizyme in ODC-SMC
      in honeycombs not only decreased the level of ODC but also inhibited polyamine
      uptake activity. These results taken together suggest that low levels of
      polyamines caused by AZ1 in SMC in honeycombs inhibit phosphorylation of FAK and
      enhance expression of alpha-actin and myosin, resulting in differentiation
      through inhibition of focal adhesions.

PMID- 21894531
TI  - Methane mitigation from ruminants using tannins and saponins.

PMID- 21894532
TI  - Polyunsaturated fatty acids induce modification in the lipid composition and the
      prostaglandin production of the conjunctival epithelium cells.
AB  - BACKGROUND: This study was conducted to evaluate whether polyunsaturated fatty
      acids (PUFA) such as gamma-linolenic acid (GLA) and eicosapentaenoic acid (EPA),
      as found in the diet, may affect the lipid composition of conjunctival epithelium
      and whether these modifications affect prostaglandin (PG) production after
      inflammatory stimulation. METHODS: Chang and IOBA-NHC conjunctival human cells
      were treated with GLA and/or EPA at 5, 10, 20, 30, 40, or 50 MUg/ml for 72 h and
      then were stimulated with interferon-gamma (IFN-gamma) for 48 h. Changes in the
      composition of neutral lipids and phospholipids were monitored by gas
      chromatography. PGE1 and PGE2 levels were measured by enzyme immunoassay.
      RESULTS: PUFA supplementations in the culture medium induced incorporation of
      these fatty acids and of their metabolites in neutral lipids and phospholipids of
      the conjunctival cells. The fatty acid composition of neutral lipids and
      phospholipids was not affected by stimulation with IFN-gamma. The production of
      PGE1 and PGE2 was affected by GLA supplementation whereas it was not modified by
      EPA supplementation. A combined supplementation of EPA and GLA did not change the
      production of PGE1 but decreased the production of PGE2. CONCLUSIONS: These
      results suggest that modulation of fatty acid composition and PG production by
      PUFA supplementation is possible in the conjunctival epithelium, which is an
      important site of inflammation in dry eye syndrome.

PMID- 21894533
TI  - Optical low-coherence reflectometry enables preoperative detection of zonular
      weakness in pseudoexfoliation syndrome.
AB  - PURPOSE: To evaluate optical ocular components in patients with pseudoexfoliation
      syndrome using optical low-coherence reflectometry. METHODS: A prospective cohort
      study of 224 eyes of patients planned for cataract surgery was conducted in the
      period from January 2009 until July 2009. Patients were divided in two groups:
      the first group of 47 eyes with cataract complicated with pseudoexfoliation
      syndrome and the control group of 177 eyes with uncomplicated cataract. Each
      group was further divided into two subgroups based on its refractive state:
      emmetropes and hypermetropes. The optical low-coherence reflectometry biometer
      LENSTAR LS 900 was used to define ocular optical components. RESULTS: A
      statistically significant difference of ocular optical components was established
      between the two groups of patients and its matching subgroups: AL (t = 2.25; p <
      0.05) and ACD (t = 2.24; p < 0.05) were significantly higher in the control
      group, PD was significantly higher in the control group hypermetropes than the
      PEX group hypermetropes (t = 2.21; p < 0.05) while LT (t = 3.01; p < 0.001), AST
      (t = 2.13; p < 0.05) and IOL (t = 3.06; p < 0.001) were higher in the PEX group
      of patients than in the control group. CONCLUSIONS: The optical low-coherence
      reflectometry enabled preoperative detection of zonular weakness and subsequent
      lens instability documented as a significantly shallower anterior chamber,
      thicker lens, and smaller pupillary diameter in the pseudoexfoliation syndrome
      group in the studied population.

PMID- 21894534
TI  - High rates of susceptibility to ceftazidime among globally prevalent CTX-M
      producing Escherichia coli: potential clinical implications of the revised CLSI
      interpretive criteria.
AB  - The CTX-M family of extended-spectrum beta-lactamases (ESBLs) is a significant
      global public health threat. The prevalence of specific bla (CTX-M) genes varies
      geographically, but bla (CTX-M-15) and bla (CTX-M-14) dominate in most countries.
      We applied the latest Clinical Laboratory Standards Institute (CLSI) interpretive
      criteria (M100-S20) to a diverse collection of ESBL-producing Escherichia coli
      strains obtained from clinical specimens in our laboratory. Whereas under
      previous CLSI recommendations all isolates in this strain collection would have
      been reported as ceftazidime-resistant, under the new recommendations,
      approximately 11% of CTX-M-15-producing E. coli and 93% of CTX-M-14-producing E.
      coli respectively tested as ceftazidime-susceptible. We also found that, whilst
      many CTX-M-14-producers had minimum inhibitory concentrations (MICs) less than
      the breakpoint of 4 mg/L, the MIC distribution for these strains was higher than
      that of wild-type E. coli, with one CTX-M-14-producing isolate having an MIC of
      >64 mg/L. Although the new CLSI recommendations imply that ceftazidime can be
      safely used to treat serious infections due to CTX-M-producing E. coli, clinical
      outcome data are lacking. Consequently, the widespread use of ceftazidime in this
      setting could have profound clinical implications.

PMID- 21894535
TI  - The 'ability' paradigm in vocational rehabilitation: challenges in an Ontario
      injured worker retraining program.
AB  - INTRODUCTION: In recent years, a focus on workers' ability, rather than
      impairment, has guided disability management services. However, a challenge with
      the notion of 'ability' is identification of the border between ability and
      inability. This article considers this gray zone of disability management in the
      case of a workers' compensation vocational retraining program for injured workers
      in Ontario. METHODS: In-depth interviews and focus groups were conducted with a
      purposive sample of 71 participants who were directly involved with the
      vocational retraining process. Workers in the program had on average incurred
      injury 3 years earlier. Procedural and legal documents were also analyzed.
      Principles of grounded theory and discourse analysis guided the data gathering
      and analysis. RESULTS: A program focus on worker abilities did not allow for
      consideration of unresolved medical problems. Concepts such as maximum medical
      rehabilitation distracted attention from workers' ongoing chronic and unstable
      health situations, and incentive levers to employers directed some of the least
      capable workers into the program. As well, communication pathways for discussing
      health problems were limited by rules and provider reluctance to reveal problems.
      Therefore, workers completing the program were deemed 'employable', while ongoing
      and problematic health conditions preventing employment remained relatively
      uncharted and invisible. CONCLUSIONS: This study reinforces how the shift in
      disability management paradigm to a focus on ability and return to work requires
      consideration of environmental conditions, including policies and programs and
      implementation. A focus on the environment in which worker ability can be enacted
      might be as important as a focus on improving individual worker characteristics.

PMID- 21894536
TI  - Health care reform: can a communitarian perspective be salvaged?
AB  - The United States is culturally oriented more toward individual rights and values
      than to communitarian values. That proclivity has made it hard to develop a
      common good, or solidarity-based, perspective on health care. Too many people
      believe they have no obligation to support the health care of others and resist a
      strong role for government, higher taxation, or reduced health benefits. I argue
      that we need to build a communitarian perspective on the concept of solidarity,
      which has been the concept underlying European health care systems, by focusing
      not on individual needs, but rather, on those of different age groups--that is,
      what people need at different stages of life.

PMID- 21894537
TI  - An Auxetic structure configured as oesophageal stent with potential to be used
      for palliative treatment of oesophageal cancer; development and in vitro
      mechanical analysis.
AB  - Oesophageal cancer is the ninth leading cause of malignant cancer death and its
      prognosis remains poor. Dysphagia which is an inability to swallow is a
      presenting symptom of oesophageal cancer and is indicative of incurability. The
      goal of this study was to design and manufacture an Auxetic structure film and to
      configure this film as an Auxetic stent for the palliative treatment of
      oesophageal cancer, and for the prevention of dysphagia. Polypropylene was used
      as a material for its flexibility and non-toxicity. The Auxetic (rotating-square
      geometry) structure was made by laser cutting the polypropylene film. This flat
      structure was welded together to form a tubular form (stent), by an adjustable
      temperature control soldering iron station: following this, an annealing process
      was also carried out to ease any material stresses. Poisson's ratio was estimated
      and elastic and plastic deformation of the Auxetic structure was evaluated. The
      elastic and plastic deformation behaviours of the Auxetic polypropylene film were
      evaluated by applying repetitive uniaxial tensile loads. Observation of the
      structure showed that it was initially elastically deformed, thereafter plastic
      deformation occurred. This research discusses a novel way of fabricating an
      Auxetic structure (rotating-squares connected together through hinges) on
      Polypropylene films, by estimating the Poisson's ratio and evaluating the plastic
      deformation relevant to the expansion behaviour of an Auxetic stent within the
      oesophageal lumen.

PMID- 21894538
TI  - Biphasic calcium phosphate coating on cobalt-base surgical alloy during
      investment casting.
AB  - The biphasic calcium phosphate (BCP) yields higher bioactivity and efficiency
      than the Hydroxyapatite (HA) alone. The HA/beta-TCP ratio significantly affects
      BCP bioactivity as well as the extent of BCP resorption. In this study, the BCP
      coating on ASTM F-75 cobalt base alloy during the investment casting process was
      investigated. For this purpose, molten metal was poured at 1,470 degrees C into
      previously coated investment molds preheated to 750, 850, 950, 1,050 degrees C in
      order to investigate the effect of mold preheating temperatures on coating phase
      transformations. For in vitro evaluation, samples were immersed in the simulated
      body fluid (SBF) at 37 degrees C for 4 weeks and characterized by XRD, SEM, EDS,
      and optical microscopy. The weight percentages of HA and beta-TCP of the
      specimens were calculated to find that the HA/beta-TCP ratio significantly
      depended on the mold preheating temperature as it caused changes in the
      dissolution behavior of BCP coating and the bone-like apatite precipitation on
      coating during in vitro evaluation.

PMID- 21894539
TI  - Preparation and properties of calcium phosphate cements incorporated gelatin
      microspheres and calcium sulfate dihydrate as controlled local drug delivery
      system.
AB  - To develop high macroporous and degradable bone cements which can be used as the
      substitute of bone repairing and drug carriers, cross-linked gelatin microspheres
      (GMs) and calcium sulfate dihydrate (CSD) powder were incorporated into calcium
      phosphate bone cement (CPC) to induce macropores, adjust drug release and control
      setting time of alpha-TCP-liquid mixtures after degradation of GMs and
      dissolution of CSD. In this study, CSD was introduced into CPC/10GMs composites
      to offset the prolonged setting time caused by the incorporation of GMs, and
      gentamicin sulphate (GS) was chosen as the model drug entrapped within the GMs.
      The effects of CSD amount on the cement properties, drug release ability and
      final macroporosity after GMs degradation were studied in comparison with CPC/GMs
      cements. The resulting cements presented reduced setting time and increased
      compressive strength as the content of CSD below 5 wt%. Sustained release of GS
      was obtained on at least 21 days, and release rates were found to be chiefly
      controlled by the GMs degradation rate. After 4 weeks of degradation study, the
      resulting composite cements appeared macroporous, degradable and suitable
      compressive strength, suggesting that they have potential as controlled local
      drug delivery system and for cancellous bone applications.

PMID- 21894540
TI  - In vitro degradation behaviour of a friction stir processed magnesium alloy.
AB  - In this study, the in vitro degradation behaviour of a friction stir processed
      AZ31 magnesium alloy was investigated. Electrochemical experiments in simulated
      body fluid suggest that friction stir processing marginally enhances the
      degradation resistance of the alloy, which could be attributed to the dissolution
      of secondary phase particles. Homogenisation of the microstructure reduces
      galvanic corrosion. It is envisaged that the beneficial effect would be more
      pronounced for magnesium alloys which contain high volume fraction of galvanic
      corrosion inducing secondary phase particles.

PMID- 21894542
TI  - Iron transport in the genus Marinobacter.
AB  - Marinobacter belong to the class of Gammaproteobacteria and these motile,
      halophilic or halotolerent bacteria are widely distributed throughout the world's
      oceans having been isolated from a wide variety of marine environments. They have
      also been identified as members of the bacterial flora associated with other
      marine organisms. Here, using a combination of natural products chemistry and
      genomic analysis, we assess the nature of the siderophores produced by this genus
      and their potential relationship to phylogeny and lifestyle/ecological niche of
      this diverse group of organisms. Our analysis shows a wide level of diversity in
      siderophore based iron uptake systems among this genus with three general
      strategies: (1) production and utilization of native siderophores in addition to
      utilization of a variety of exogenous ones, (2) production and utilization of
      native siderophores only, (3) lack of siderophore production but utilization of
      exogenous ones. They all share the presence of at least one siderophore
      independent iron uptake ABC transport systems of the FbpABC iron metal type and
      lack the ability for direct transport of ferrous iron. Siderophore production and
      utilization can be correlated with phylogeny and thus it forms a type of
      chemotaxonomic marker for this genus.

PMID- 21894541
TI  - [Therapy of humeral shaft fractures].
AB  - Fractures of the humeral shaft are less frequent than those of the proximal
      humerus. The formerly recommended treatment of humeral shaft fractures was
      conservative according to Bohler. This still remains an adequate concept of
      treatment but according to a change in the technical possibilities and the
      demands of patients and physicians on fast restoration of function and low pain,
      there is a trend towards surgical stabilization of humeral shaft fractures. The
      implant of choice is discussed controversially and consists of various types of
      nails versus plating. The technique of nailing is antegrade or retrograde and
      depends on the localization of the fracture. In our opinion good indications for
      plating are combined fractures of the proximal humerus and the shaft as well as
      very distal humeral shaft fractures. A primary lesion of the radial nerve is no
      imperative indication for exploration and different studies have shown the same
      results for exploration after 2 or 3 months if there is no spontaneous remission.

PMID- 21894543
TI  - Unilateral gynecomastia in a prepubertal boy.

PMID- 21894544
TI  - Myocardial perfusion scintigraphy in Europe 2007: a survey of the European
      Council of Nuclear Cardiology.
AB  - PURPOSE: This is the second of a series of surveys designed to assess myocardial
      perfusion scintigraphy (MPS) practice in Europe. METHODS: Data were collected
      from 258 centres in 18 countries. The number of MPS studies per million
      population (pmp) was estimated assuming that the nonresponding centres performed
      either no studies (lower estimate) or the same number as the responding centres
      (upper estimate). RESULTS: The responding centres served 24% of the population of
      their countries. The total number of noncardiac nuclear medicine studies was
      between 2,160 and 8,000 studies pmp. The total number of MPS studies was between
      529 and 2,293 pmp. The median number of MPS studies per centre was 571 per year
      with 57% performing fewer than 500 studies per year and 23% of centres performing
      fewer than 250 studies per year. There was significant variation between
      countries, with higher numbers of MPS studies (lower limit of estimate above the
      mid-range of all countries combined) in Austria, Denmark, Hungary, Portugal and
      Slovenia, and lower numbers (upper limit of estimate below the mid-range of all
      countries) in Finland, Norway, Spain and Switzerland. The ratio of MPS to
      coronary angiography to revascularization procedures was 0.9 to 2.2 to 1.
      Pharmacological stress was used in 57% and technetium-99m-labelled tracers in 88%
      of studies. ECG gating was performed in 74% of studies and attenuation correction
      in 22%. CONCLUSION: MPS utilization in Europe remains low compared with coronary
      angiography although there has been a 21% increase in the number of studies pmp
      in centres that reported in both 2005 and 2007. Pharmacological agents continue
      to be the predominant form of stress. Despite the widespread use of technetium
      99m-labelled tracers, ECG gating is not universally performed. As in the 2005
      survey, imaging aids such as attenuation and motion correction and prone imaging
      are not commonly used.

PMID- 21894545
TI  - Voriconazole-induced periostitis.

PMID- 21894546
TI  - Early interim 18F-FDG PET in Hodgkin's lymphoma: evaluation on 304 patients.
AB  - PURPOSE: The use of early (interim) PET restaging during first-line therapy of
      Hodgkin's lymphoma (HL) in clinical practice has considerably increased because
      of its ability to provide early recognition of treatment failure allowing
      patients to be transferred to more intensive treatment regimens. METHODS: Between
      June 1997 and June 2009, 304 patients with newly diagnosed HL (147 early stage
      and 157 advanced stage) were treated with the ABVD regimen at two Italian
      institutions. Patients underwent PET staging and restaging at baseline, after two
      cycles of therapy and at the end of the treatment. RESULTS: Of the 304 patients,
      53 showed a positive interim PET scan and of these only 13 (24.5%) achieved
      continuous complete remission (CCR), whereas 251 patients showed a negative PET
      scan and of these 231 (92%) achieved CCR. Comparison between interim PET-positive
      and interim PET-negative patients indicated a significant association between PET
      findings and 9-year progression-free survival and 9-year overall survival, with a
      median follow-up of 31 months. Among the early-stage patients, 19 had a positive
      interim PET scan and only 4 (21%) achieved CCR; among the 128 patients with a
      negative interim PET scan, 122 (97.6%) achieved CCR. Among the advanced-stage
      patients, 34 showed a persistently positive PET scan with only 9 (26.4%)
      achieving CCR, whereas 123 showed a negative interim PET scan with 109 (88.6%)
      achieving CCR. CONCLUSION: Our results demonstrate the role of an early PET scan
      as a significant step forward in the management of patients with early-stage or
      advanced-stage HL.

PMID- 21894547
TI  - Timely recognition of cardiovascular toxicity by anticancer agents: a common
      objective of the pharmacologist, oncologist and cardiologist.
AB  - Both conventional and new anticancer drugs can frequently cause adverse
      cardiovascular effects, which can span from subclinical abnormalities to serious
      life-threatening and sometimes fatal events. This review examines the principal
      basic and clinical elements that may be of profit to identify, prevent and treat
      such toxicities. Clearly, the accomplishment of such objectives requires the
      strong commitment and cooperation of different professional figures including,
      but not limited to, pharmacologists, oncologists and cardiologists. The aspect of
      anticancer drug cardiotoxicity seems to be somehow underestimated, mainly due to
      inadequate reporting of adverse reactions from oncology drugs in the post
      marketing setting. Thus, the implementation of pharmacovigilance is indispensable
      to rapidly and fully assess the safety of newer agents in real-life patients.

PMID- 21894548
TI  - Ascending aortic aneurysm.
AB  - A 14-year-old boy presented with an unusual bulging chest noted to be increasing
      slowly over the last few years. He had no other complaints. Cardiac
      echocardiography and cardiac magnetic resonance imaging (MRI) showed aneurysmal
      dilation of the ascending aorta with moderate aortic valve insufficiency and
      moderate pericardial effusion. The boy underwent reconstruction of his ascending
      aorta in the form of a Bentall procedure using a 25-mm Carbomedic valve conduit.

PMID- 21894549
TI  - Left ventricle pseudoaneurysm after aortic valvuloplasty.
AB  - Acquired left ventricular aneurysm is extremely rare in children. This report
      describes an infant with acquired left ventricular aneurysm after percutaneous
      aortic balloon valvuloplasty for critical aortic stenosis. The potential risk
      factors for myocardial injury during cardiac catheterization and potential
      complications are discussed.

PMID- 21894550
TI  - Usefulness of McRAPD for typing and importance of biofilm production in a case of
      nosocomial ventriculoperitoneal shunt infection caused by Candida lusitaniae.
AB  - A case report of ventriculoperitoneal shunt infection caused by Candida
      lusitaniae in a 6-year-old patient with cerebral astrocytoma and obstructive
      hydrocephalus is presented briefly with emphasis on the course of antifungal
      treatment. Seven isolates recovered subsequently from the cerebrospinal fluid
      were studied retrospectively. To confirm identity, isolates were typed using
      pulsed-field gel electrophoresis and melting curve of random amplified
      polymorphic DNA (McRAPD). Further, the ability to form biofilm and its
      susceptibility to systemic antifungals were evaluated. Using McRAPD, identity of
      C. lusitaniae isolates showing slight microevolutionary changes in karyotypes was
      undoubtedly confirmed; successful application of numerical interpretation of
      McRAPD for typing is demonstrated here for the first time. The strain was also
      recognized as a strong biofilm producer. Moreover, minimum biofilm inhibitory
      concentrations were very high, in contrast to low antifungal minimum inhibitory
      concentrations of isolates. It can be concluded that McRAPD seems to be a simple
      and reliable method not only for identification but also for typing of yeasts. A
      ventriculoperitoneal shunt colonized by C. lusitaniae was revealed as the source
      of this nosocomial infection, and the ability of the strain to form biofilm on
      its surface likely caused treatment failure.

PMID- 21894551
TI  - A novel molecular mechanism to explain biotin-unresponsive holocarboxylase
      synthetase deficiency.
AB  - Biotin (vitamins H and B7) is an important micronutrient as defects in its
      availability, metabolism or adsorption can cause serious illnesses, especially in
      the young. A key molecule in the biotin cycle is holocarboxylase synthetase
      (HLCS), which attaches biotin onto the biotin-dependent enzymes. Patients with
      congenital HLCS deficiency are prescribed oral biotin supplements that, in most
      cases, reverse the clinical symptoms. However, some patients respond poorly to
      biotin therapy and have an extremely poor long-term prognosis. Whilst a small
      number of mutations in the HLCS gene have been implicated, the molecular
      mechanisms that lead to the biotin-unresponsive phenotype are not understood. To
      improve our understanding of HLCS, limited proteolysis was performed together
      with yeast two-hybrid analysis. A structured domain within the N-terminal region
      that contained two missense mutations was identified in patients who were
      refractory to biotin therapy, namely p.L216R and p.L237P. Genetic studies
      demonstrated that the interaction between the enzyme and the protein substrate
      was disrupted by mutation. Further dissection of the binding mechanism using
      surface plasmon resonance demonstrated that the mutations reduced affinity for
      the substrate through a >15-fold increase in dissociation rate. Together, these
      data provide the first molecular explanation for HLCS-deficient patients that do
      not respond to biotin therapy.

PMID- 21894553
TI  - Chocolate and coronary heart disease: a systematic review.
AB  - Coronary heart disease (CHD) is the leading cause of death in the United States.
      The high content of polyphenols and flavonoids present in cocoa has been reported
      to play an important protective role in the development of CHD. Although studies
      have demonstrated beneficial effects of chocolate on endothelial function, blood
      pressure, serum lipids, insulin resistance, and platelet function, it is unclear
      whether chocolate consumption influences the risk of CHD. This article reviews
      current evidence on the effects of cocoa/chocolate on clinical and subclinical
      CHD, CHD risk factors, and potential biologic mechanisms. It also discusses major
      limitations of currently available data and future directions in the field.

PMID- 21894554
TI  - Functional dissociation between Kana and Kanji: agraphia following a thalamic
      hemorrhage.
AB  - We report the case of a 61-year-old woman with a left thalamic hemorrhage causing
      agraphia of Kanji (morphograms). Single-photon emission computed tomography
      (SPECT) showed a decrease in the blood flow in the left thalamus from the
      superior temporal convolution to the parietal lobe, as well as in the frontal
      lobe while computed tomography showed no remarkable lesions in the cortex. The
      agraphia in this case may be due to the thalamic lesion itself, but the SPECT
      findings strongly suggest that a secondary cortical lesion may be involved in
      producing the higher cognitive disorder.

PMID- 21894552
TI  - Genetic variants in candidate genes influencing NAFLD progression.
AB  - Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder including simple
      steatosis and nonalcoholic steatohepatitis (NASH). Advanced stages of NASH result
      ultimately in fibrosis, cirrhosis, and hepatocarcinoma. A diagnosis of NASH
      entails an increased risk of both liver-related and cardiovascular mortality as
      worsening of the metabolic syndrome. Because of its escalation, many
      investigations have been performed to elucidate the pathophysiologic origins of
      the disease progression. Human epidemiologic studies describing polymorphisms in
      a number of genes involved in metabolic dysfunctions have contributed to clarify
      the causes leading to the disease evolution. In this review, we attempt to
      outline critically the most recently identified genetic variants in NAFLD
      patients to identify possible risk factors promoting the progression of the
      disease. The evaluation of altered genotypes together with other clinical
      variables may facilitate the clinical management of these patients.

PMID- 21894555
TI  - Hashimoto's encephalopathy presenting with micrographia as a typical feature of
      parkinsonism.
AB  - We describe here a 63-year-old woman who presented with gait disturbance and
      micrographia. Laboratory tests demonstrated the presence of anti-thyroperoxidase
      (TPO) antibodies and vitamin B(12) deficiency accompanied by the presence of anti
      parietal cell antibodies. Lymphocytosis with increased protein was detected in
      cerebral spinal fluid (CSF). Serum autoantibodies against the anti-NH(2) terminal
      of alpha-enolase (NAE), a specific diagnostic marker for Hashimoto's
      encephalopathy (HE), were also detected. Since underlying autoimmune conditions
      were suspected to be associated with Hashimoto's disease, steroid therapy was
      conducted, and the neurological symptoms improved a few days after the therapy
      was started. Attention should be given to the possibility that typical
      parkinsonism showing micrographia is caused by HE.

PMID- 21894556
TI  - Standing worsens cognitive functions in patients with neurogenic orthostatic
      hypotension.
AB  - In previous studies, addressing the association between orthostatic hypotension
      and cognitive decline, patients underwent neuropsychological evaluation in
      sitting position, and blood pressure values and cognition were not measured
      concurrently. Furthermore, no studies assessed the acute effects of orthostatic
      hypotension on cognitive performances. The aim of our study was to evaluate the
      effect of a documented fall in systolic blood pressure (SBP) of at least 20 mmHg
      on a battery of cognitive tests in patients with neurogenic orthostatic
      hypotension. Ten consecutive patients with neurogenic orthostatic hypotension,
      normal brain imaging, and a normal Mini Mental State Examination in supine
      position were enrolled in the study. Patients underwent a detailed
      neuropsychological assessment (Brief Mental Deterioration battery and
      computerized tests) over two test sessions: the first while tilted to an angle
      able to cause a fall of at least 20 mmHg in SBP; the second while supine, after
      30 min of rest. Parallel forms of the tests were presented on each testing
      session. Patients scored significantly worse in the visual search test, analogies
      test, immediate visual memory, and the measure of global cognitive functioning of
      Brief Mental Deterioration battery during the orthostatic challenge compared to
      the supine position. Orthostatic hypotension was associated with a significant
      worsening of cognitive performances, affecting both global cognitive functioning
      and specific tasks, mainly exploring executive functions. The assessment of
      cognitive function in patients with neurogenic orthostatic hypotension should be
      performed considering the body's position of the subject.

PMID- 21894557
TI  - [Anticancer activity of Salvia officinalis essential oil against HNSCC cell line
      (UMSCC1)].
AB  - BACKGROUND: Every year there are several hundred thousand new cases of oral
      cancer worldwide. Clinical oncology is still challenged by toxicity and side
      effects of multimodal therapy strategies in which is associated with poor
      prognosis for patients. There is an urgent necessity to develop novel therapy
      strategies. As the majority of anticancer drugs are of natural origin, natural
      products represent a valuable source for the identification and development of
      novel treatment options for cancer. The aim of this investigation was to study
      the cytotoxicity of Salvia officinalis L. (sage) essential oil. METHODS: Salvia
      officinalis essential oil was gained by aqueous extraction from plant material
      and subsequently analyzed by gas chromatography. The cytotoxicity of the
      essential oil on the squamous human cell carcinoma cell line of the oral cavity
      (UMSCC1) was assessed with the XTT assay. These experiments revealed the half
      maximal inhibitory concentration (IC(50)) of the essential oil. It was used in
      the microarray-based analysis of gene expression of UMSSC1 cells. The results
      were submitted to a signaling pathway analysis. RESULTS: The main constituents of
      Salvia officinalis essential oil include the monoterpenes thujone, beta-pinene,
      and 1,8-cineol. Low concentrations of the essential oil increased vitality of the
      UMSCC1 cells. Beyond the concentration of the IC(50) of 135 ug/ml, sage essential
      oil reduced UMSSC1 cells viability to a minimum. In the microarray gene
      expression analysis, genes involved in cancer, cellular growth and proliferation,
      cell death, cell morphology, cell cycle, gene expression, and DNA repair were the
      most prominent. The three most significantly regulated pathways by sage were aryl
      hydrocarbon receptor signaling, cell cycle (G1/S checkpoint) regulation, and p53
      signaling. CONCLUSION: To the best of our knowledge, this study suggests for the
      first time the ability of Salvia officinalis essential oil to inhibit human HNSCC
      cell growth. The therapeutic potential of sage essential oil might exceed that of
      its common use in otorhinolaryngology.

PMID- 21894558
TI  - Laparoendoscopic single-site (LESS) hysteropexy.
AB  - Uterine prolapse is one of the common reasons for hysterectomy throughout the
      world. However, recent data has shown that uterine-sparing techniques appear to
      be equivocal to that of hysterectomy. Older reports of intra-abdominal uterine
      suspension describe open approaches and more recent descriptions involve robotic
      and laparoscopic approaches utilizing mesh. We describe the first reported
      laparoendoscopic single-site (LESS) sacral hysteropexy utilizing a strip of
      polypropylene mesh placed posteriorly on the uterus and attached to the sacral
      promontory. A 45-year-old female with grade 3 uterine prolapse, cystocele, and
      rectocele underwent the procedure. The procedure involved access utilizing a
      single-port system placed transumbilically, and dissection using articulating
      laparoscopic instruments. The hysteropexy was completed by placing a 3-cm wide
      strip of polypropylene mesh along the posterior vaginal wall and cervicouterine
      junction, and suturing the proximal end to the anterior longitudinal ligament
      overlying the sacral promontory. The patient was discharged home within 18 h of
      the procedure. At 6 month follow-up, the patient has excellent anatomic support,
      with no evidence for recurrence of prolapse. LESS hysteropexy appears to be a
      safe, effective procedure for uterine prolapse and provides patients with
      excellent outcome with no visible scar. Additional studies will determine whether
      the LESS approach provides any benefit when compared with robotic or traditional
      laparoscopic approaches with respect to blood loss, pain, and time of full
      recovery.

PMID- 21894559
TI  - Polycyclic aromatic hydrocarbons and risk to threatened and endangered Chinook
      salmon in the Lower Columbia River estuary.
AB  - Polycyclic aromatic hydrocarbons (PAHs), derived from oil and fuel combustion,
      are ubiquitous nonpoint source pollutants that can have a number of detrimental
      effects on fish and wildlife. In this study, we monitored PAH exposure in
      outmigrant juvenile Chinook salmon from the Lower Columbia River to evaluate the
      risk that these contaminants might pose to the health and recovery of threatened
      and endangered salmonids. Juvenile Chinook salmon (Oncorhynchus tshawytscha) were
      collected by beach seine from five sites in the Lower Columbia River from
      Bonneville Dam to the mouth of the estuary (Warrendale, the Willamette-Columbia
      Confluence, Columbia City, Beaver Army Terminal, and Point Adams) and from a site
      in the Lower Willamette near downtown Portland (Morrison Street Bridge). Sediment
      samples were also collected at the same sites. Concentrations of PAHs in sediment
      samples were relatively low at all sites with average total PAH concentrations
      <1000 ng/g dry weight (wt.). However, we found PAHs in stomach contents of salmon
      from all sites at concentrations ranging from <100 to >10,000 ng/g wet wt.
      Metabolites of low and high molecular-weight PAHs were also detected in bile of
      salmon from all sites; for metabolites fluorescing at phenanthrene (PHN)
      wavelengths, concentrations ranged from 1.1 to 6.0 MUg/mg bile protein. Levels of
      PAHs in stomach contents and PAH metabolites in bile were highest in salmon from
      the Morrison Street Bridge site in Portland and the Willamette-Columbia
      Confluence, Columbia City, and Beaver Army Terminal sites. Mean PAH
      concentrations measured in some stomach content samples from the Columbia City,
      Beaver Army Terminal, and Morrison Street Bridge sites were near the threshold
      concentration (approximately 7200-7600 ng/g wet wt.) associated with variability
      and immune dysfunction in juvenile salmonids (Meador et al., Can J Fish Aquat Sci
      63:2364-2376, 2006; Bravo et al., Environ Toxicol Chem 30:704-714, 2011). Mean
      levels of biliary fluorescent aromatic compounds (FACs)-PHN in juvenile Chinook
      collected at the Morrison Street Bridge site in Portland, at the Confluence and
      Columbia City sites, and at the Beaver Army Terminal site were at or above a
      threshold effect concentration of 2 MUg/mg protein for FACs-PHN linked to growth
      impairment, altered energetics, and reproductive effects (Meador et al., Environ
      Toxicol Chem 27(4):845-853, 2008). These findings suggest that PAHs in the food
      chain are a potential source of injury to juvenile salmon in the Lower Columbia
      and Lower Willamette rivers.

PMID- 21894560
TI  - Perimedullary arteriovenous fistulas in children: report on six cases.
AB  - BACKGROUND: Perimedullary arteriovenous fistulas (PMAVFs) are rare spinal lesions
      and even more uncommon in children. OBJECTIVE: The aim of this study was to
      document rare occurrences of this type of arteriovenous malformation in six
      children treated at our institution. METHODS: The clinical data, radiological
      findings, and treatment in six cases of PMAVFs were reviewed. Six patients with
      PMAVFs were managed at our institution over a 5-year period. The patients (four
      girls and two boys), ranging in age from 6 to 15 years, presented with initially
      fluctuating, and eventually permanent and progressive, sudden-onset paraparesis,
      sensory disturbances, and sphincter dysfunction. The duration of symptoms before
      diagnosis ranged from 1 week to 13 years. RESULTS: All the patients underwent
      magnetic resonance imaging and spinal selective angiography, which demonstrated
      the characteristic imaging of an arteriovenous fistula. Embolization of the
      arteriovenous fistula was initially attempted in three patients with successful
      occlusion of the fistula in two. For the remaining cases, open surgery was
      performed, with complete occlusion of the fistula. There was no morbidity,
      regardless of the treatment performed. All the patients experienced neurological
      improvement after treatment. CONCLUSIONS: No specific clinical or radiological
      characteristic of PMAVFs in the pediatric population was observed when our series
      was compared with a general series. Early diagnosis and timing of the therapeutic
      intervention seemed to avoid the development of irreversible ischemic
      myeloradiculopathy and prevented hemorrhage. Treatment for PMAVFs is difficult to
      standardize because these are extremely rare lesions with different
      angioarchitecture configurations.

PMID- 21894561
TI  - Metastasis to sentinel lymph nodes in breast cancer is associated with maturation
      arrest of dendritic cells and poor co-localization of dendritic cells and CD8+ T
      cells.
AB  - The regional immune systems of patients with breast cancer are immunosuppressed.
      Dendritic cells are professional antigen-presenting cells and present cancer
      associated antigens to the adaptive immune system in sentinel lymph nodes.
      Dendritic cells may promote, or inhibit, an adaptive immune response to specific
      antigens. Our aim was to assess whether dendritic cells were associated with
      nodal metastasis in patients with breast cancer. Sentinel lymph nodes of 47
      patients with breast cancer with varying degrees of nodal disease and ten
      controls were evaluated using immunohistochemistry for the accumulation of
      dendritic cells in general (CD1a(+)), mature dendritic cells (CD208(+)), and
      plasmacytoid dendritic cells (CD123(+)). Cytotoxic T cell and regulatory T cell
      accumulation were also evaluated. Sentinel lymph nodes with macrometastases
      demonstrated fewer mature dendritic cells than sentinel lymph nodes without
      metastasis (p = 0.028), but not controls. There were fewer mature dendritic cells
      to cytotoxic T cells in sentinel lymph nodes with metastasis than those without
      (p = 0.033). Also, there were more regulatory T cells to mature dendritic cells
      in sentinel lymph nodes with metastasis than those without (p = 0.02). In
      conclusion, our study suggests that sentinel lymph nodes with metastasis have
      arrest of maturation of dendritic cells, fewer mature dendritic cell interactions
      with cytotoxic T cells, and more regulatory T cells than sentinel lymph nodes
      without metastasis in patients with breast cancer. These findings extend our
      understanding of regional immunosuppression and suggest that most regional
      immunosuppressive changes are associated with nodal metastasis in breast cancer.

PMID- 21894562
TI  - Detection of Slit2 promoter hypermethylation in tissue and serum samples from
      breast cancer patients.
AB  - Promoter hypermethylation has been shown to be a common mechanism for
      inactivation of tumor suppressor genes in breast cancer. The aim of this study
      was to investigate the prevalence of Slit2 promoter hypermethylation in both the
      tumor and serum samples of breast cancer patients with ductal carcinoma in situ
      (DCIS) or invasive breast carcinoma (IBC). The methylation status of Slit2 was
      investigated in 210 tissue samples (15 breast with no pathological findings, 26
      DCIS, and 169 IBC samples) and 123 corresponding serum samples (15 breast with no
      pathological findings, 26 DCIS, and 82 IBC samples) using methylation-specific
      polymerase chain reaction. Immunohistochemical staining for Slit2 was also
      performed using tissue microarray blocks to determine whether Slit2 promoter
      hypermethylation correlated with loss of Slit2 expression. Slit2 promoter
      hypermethylation was not detected in breast tissue and serum samples from
      patients with no pathological findings. DCIS or IBC showed a statistically higher
      frequency of Slit2 promoter hypermethylation compared to breast with no
      pathological findings in both the tissue and serum samples; however, there were
      no statistically significant differences between DCIS and IBC samples. Similar
      Slit2 promoter hypermethylation patterns were seen in the tissue samples and
      corresponding serum specimens (p < 0.001). Slit2 promoter hypermethylation was
      associated with loss of Slit2 expression. These results suggest that Slit2
      promoter hypermethylation appears to be responsible for functionally silencing
      Slit2 expression. Slit2 promoter hypermethylation may be considered as a possible
      serum marker for early detection of breast cancer.

PMID- 21894563
TI  - Adnexal torsion in a woman undergoing ovarian hyperstimulation with clomiphene
      citrate therapy: a case report and review of the literature.
AB  - Ovarian stimulation is a unique aid for patients treated for anovulation and an
      important tool in various assisted reproduction treatments. Clomiphene citrate,
      an orally active, non-steroidal triphenylethylene derivate, is a commonly
      prescribed agent for ovulation induction. Clomiphene citrate is considered a safe
      agent and has rarely been associated with significant side effects. This report
      describes a case of unilateral adnexal torsion after ovulation induction with
      clomiphene citrate; we performed unwinding of the adnexum, which appeared
      ischemic via laparoscopy. Unfortunately, the affected adnexum became hemorrhagic
      after this approach, which invariably led to its resection.

PMID- 21894564
TI  - Molecular modeling of Trypanosoma cruzi glutamate cysteine ligase and
      investigation of its interactions with glutathione.
AB  - Trypanosoma cruzi glutamate cysteine ligase (TcGCL) is considered a potential
      drug target to develop novel antichagasic drugs. We have used a variety of
      computational methods to investigate the interactions between TcGCL with
      Glutathione (GSH). The three-dimensional structure of TcGCL was constructed by
      comparative modeling methods using the Saccharomyces cerevisiae glutamate
      cysteine ligase as template. Molecular dynamics simulations were used to validate
      the TcGCL model and to analyze the molecular interactions with GSH. Using RMSD
      clustering, the most prevalent GSH binding modes were identified paying attention
      to the residues involved in the molecular interactions. The GSH binding modes
      were used to propose pharmacophore models that can be exploited in further
      studies to identify novel antichagasic compounds.

PMID- 21894565
TI  - Is there a role for dynamic swallowing MRI in the assessment of gastroesophageal
      reflux disease and oesophageal motility disorders?
AB  - OBJECTIVES: To evaluate the diagnostic value of dynamic MRI swallowing in
      patients with symptoms of Gastroesophageal Reflux Disease (GERD). METHODS: Thirty
      seven patients (17 m/20f) with typical signs of GERD underwent MR swallowing in
      the supine position at 1.5 T with a phased-array body coil. Using dynamic,
      gradient echo sequences (B-FFE) in the coronal, sagittal and axial planes, the
      bolus passages of buttermilk spiked with gadolinium chelate were tracked. MRI, pH
      metry and manometry were performed within 31 days and results were compared.
      RESULTS: MRI results were concordant with pH-metry in 82% (23/28) of patients
      diagnosed with abnormal oesophageal acid exposure by pH-metry. Five patients
      demonstrated typical symptoms of GERD and had positive findings with pH
      monitoring, but false negative results with MRI. In four of six patients (67%),
      there was a correct diagnosis of oesophageal motility disorder, according to
      manometric criteria, on dynamic MRI. The overall accuracy of MRI diagnoses was
      79% (27/34). A statistically significant difference was found between the size of
      hiatal hernia, grade of reflux in MRI, and abnormal acid exposure on pH
      monitoring. CONCLUSIONS: MR fluoroscopy may be a promising radiation-free tool in
      assessing the functionality and morphology of the GE junction. KEY POINTS: *
      Swallowing MRI can assess anatomy and function of the gastroesophageal-junction *
      Swallowing MRI can help identifying reflux and motility disorders * Definition of
      the size of hiatal hernias is possible in all three planes in MR. * Short
      duration of swallowing MRI enables its application in routine clinical practice.

PMID- 21894566
TI  - Statistically significant?

PMID- 21894567
TI  - Razorbill (Alca torda) feathers as an alternative tool for evaluating exposure to
      organochlorine pesticides.
AB  - The aim of this study was to explore the usefulness of feathers as a
      biomonitoring tool for organochlorine pesticides (OC) in a razorbill population
      (Alca torda). Fifteen OC were analyzed in feathers, including alpha-, beta- and
      delta-hexachlorocyclohexane, lindane, aldrin, dieldrin, endrin, endosulfan I and
      II, endosulfan sulfate, p,p'-DDT, DDD, DDE, heptachlor and its epoxide. The
      geometric mean concentrations observed in this study were ?DDT 67.40 ng/g, ?HCH
      62.88 ng/g, ?Heptachlor 61.75 ng/g, ?Endosulfan 19.70 ng/g, and ?Drins 10.17
      ng/g. The higher OC levels found in this study compared with other studies are
      probably affected by the razorbill diet and migration status. However, levels
      found in the feathers of the present study are related to concentrations in
      internal tissues below those which cause adverse reproductive and behavioral
      effects or other signs of organochlorine-pesticide poisoning in birds. Age does
      affect the concentration of OC pesticides in feathers. Thus, feathers would
      appear to be a promising tool for OC biomonitoring in seabirds, since it is
      possible to quantify OC compounds.

PMID- 21894569
TI  - Key challenges of housing and health from WHO perspective.

PMID- 21894568
TI  - Inequalities in therapeutic treatment during cardiac inpatient rehabilitation in
      Germany.
AB  - OBJECTIVE: Cardiac patients of low socio-economic status (SES) display low health
      status and increased need for rehabilitation. This study's objective was to
      examine whether and to what extent inequalities in the provision of
      rehabilitative health care occur in Germany. METHODS: We conducted an
      observational study with two points of measurement on 543 patients in cardiac
      inpatient rehabilitation. We used logistic regression and analysis of covariance
      to explore whether patients experience unequal therapeutic rehabilitative
      treatment. RESULTS: Patients of low SES were less frequently physically active,
      more likely to smoke and displayed a higher number of physical and psychological
      symptoms when entering rehabilitation. They were less likely to receive a number
      of therapies with differences being significant for core therapies of
      cardiovascular rehabilitation. Patients of higher SES received fewer hours of
      dietary counselling on average. CONCLUSIONS: While the latter difference might be
      in line with the needs of different socio-economic groups, most differences are
      unlikely to be tailored to patients' needs. Potential causes of inequalities in
      service provision like structural factors and aspects of the doctor-patient
      encounter should be further investigated.

PMID- 21894570
TI  - Studies on activity, distribution, and zymogram of protease, alpha-amylase, and
      lipase in the paddlefish Polyodon spathula.
AB  - A series of biochemical determination and electrophoretic observations have been
      conducted to analyze the activities and characteristics of protease, alpha
      amylase, and lipase of paddlefish Polyodon spathula. The results obtained have
      been compared with those of bighead carp (Aristichthys nobilis) and hybrid
      sturgeon (Huso dauricus ? * Acipenser schrenki Brandt ?), in order to increase
      available knowledge of the physiological characteristics of this sturgeon species
      and to gain information with regard to its nutrition. Further, a comparative
      study of enzymatic activity, distribution, and characterization between
      commercial feed-reared paddlefish (CG) and natural live food-reared (NG)
      paddlefish was conducted. Results showed that higher proteolytic activity was
      observed in the pH range 2.5-3.0 and at a pH of 7.0 for paddlefish. Levels of
      acid protease activity of paddlefish were similar to that of hybrid sturgeon, and
      significantly higher than that of bighead carp. The inhibition assay of
      paddlefish showed that the rate of inhibition of tosyl-phenylalanine chloromethyl
      ketone was approximately 2.6-fold that of tosyl-lysine chloromethyl ketone. There
      was no significant difference observed for acid protease activity between PG and
      CG groups, whereas the activity of alkaline protease, alpha-amylase, and lipase
      in the PG group were significantly lower than those in the CG group. The
      substrate sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis
      further showed that there were certain types of enzymes, especially alpha
      amylase, with similar molecular mass in the paddlefish and hybrid sturgeon. It
      can be inferred that acid digestion was main mechanism for protein hydrolysis in
      paddlefish, as reported for other fishes with a stomach. This indicates that the
      paddlefish requires higher alkaline protease, alpha-amylase, and lipase activity
      to digest natural live food.

PMID- 21894571
TI  - The impact of prior long-term versus short-term statin use on the mortality of
      bacteraemic patients.
AB  - BACKGROUND: The aim of this investigation was to assess the effect of prior
      statin use on the 30-day in-hospital mortality among bacteraemic patients and to
      determine the impact of long-term versus short-term statin use on the mortality
      of bacteraemic patients. PATIENTS AND METHODS: A retrospective study of 342
      bacteraemic patients who presented to the emergency department (ED) within a
      period of 7 years was undertaken. Twenty-three patients did not meet the
      inclusion criteria. The remaining 319 patients were divided into three groups
      according to statin use and duration of therapy prior to the bacteraemic episode:
      group 1 (n = 123) had long-term statin use >= 12 weeks, group 2 (n = 35) had
      short-term statin use < 12 weeks, and group 3 (n = 161) had no statin use.
      RESULTS: The overall 30-day in-hospital all-cause mortality of patients with
      statins was lower than patients without statin therapy (13 vs. 24%, p = 0.001).
      The mortality rate in group 1 was lower than in group 2 (11 vs. 17%, p = 0.04).
      After adjusting for confounding variables, the results of a multiple Cox
      regression analysis revealed that the absence of statin use (hazard ratio [HR] =
      2.98; 95% confidence interval [CI] 1.59-5.56, p = 0.001) was associated with
      increased 30-day in-hospital all-cause mortality in bacteraemic patients.
      CONCLUSIONS: Statins reduce the 30-day in-hospital all-cause mortality of
      bacteraemic patients. Long-term statin use prior to the bacteraemia improves the
      survival of bacteraemic patients more than short-term statin use.

PMID- 21894573
TI  - Oxygen exposure increases resistance of Desulfovibrio vulgaris Hildenborough to
      killing by hydrogen peroxide.
AB  - Inactivation of PerR by oxidative stress and a corresponding increase in
      expression of the perR regulon genes is part of the oxidative stress defense in a
      variety of anaerobic bacteria. Diluted anaerobic, nearly sulfide-free cultures of
      mutant and wild-type Desulfovibrio vulgaris (10(5)-10(6) colony-forming units/ml)
      were treated with 0 to 2,500 MUM H(2)O(2) for only 5 min to prevent readjustment
      of gene expression. Survivors were then scored by plating. The wild type and perR
      mutant had 50% survival at 58 and 269 MUM H(2)O(2), respectively, indicating the
      latter to be 4.6-fold more resistant to killing by H(2)O(2) under these
      conditions. Significantly increased resistance of the wild type (38-fold; 50%
      killing at 2188 MUM H(2)O(2)) was observed if cells were pretreated with full air
      for 30 min, conditions that did not affect cell viability. The resistance of the
      perR mutant increased less (4.6-fold; 50% killing at 1230 MUM H(2)O(2)), when
      similarly pretreated. Interestingly, no increased resistance of either was
      achieved by exposure with 10.6 MUM H(2)O(2) for 30 min, the highest concentration
      that could be used without killing the cells. Hence, in environments with low D.
      vulgaris biomass only the presence of external O(2) effectively activates the
      perR regulon. As a result, mutant strains lacking one of the perR regulon genes
      ahpC, dvu0772, rbr1 or rbr2 displayed decreased resistance to H(2)O(2) stress
      only following pretreatment with air.

PMID- 21894572
TI  - Dissection of genetic associations with language-related traits in population
      based cohorts.
AB  - Recent advances in the field of language-related disorders have led to the
      identification of candidate genes for specific language impairment (SLI) and
      dyslexia. Replication studies have been conducted in independent samples
      including population-based cohorts, which can be characterised for a large number
      of relevant cognitive measures. The availability of a wide range of phenotypes
      allows us to not only identify the most suitable traits for replication of
      genetic association but also to refine the associated cognitive trait. In
      addition, it is possible to test for pleiotropic effects across multiple
      phenotypes which could explain the extensive comorbidity observed across SLI,
      dyslexia and other neurodevelopmental disorders. The availability of genome-wide
      genotype data for such cohorts will facilitate this kind of analysis but
      important issues, such as multiple test corrections, have to be taken into
      account considering that small effect sizes are expected to underlie such
      associations.

PMID- 21894574
TI  - Morphology and phylogenetics of two holoparasitic plants, Balanophora japonica
      and Balanophora yakushimensis (Balanophoraceae), and their hosts in Taiwan and
      Japan.
AB  - Balanophora japonica and B. yakushimensis are two putatively agamospermic taxa
      previously reported from southern Japan. Their inflorescences superficially
      represent those of B. laxiflora and B. fungosa. In this study we confirmed their
      presence in Taiwan by morphological and phylogenetic analysis using nuclear 18S
      rDNA and nrITS sequences with related taxa. B. japonica, B. yakushimensis, and B.
      laxiflora formed a well-supported clade that is distinct from other Balanophora.
      All three taxa also show considerable differences on morphological and nucleotide
      sequence differences, therefore the name of B. yakushimensis is retained. The
      results provide new insights on the intrageneric classification of Balanophora
      and suggest the positioning of female flowers should be down-weighted. We also
      successfully identify the hosts of B. japonica and B. yakushimensis by amplifying
      chloroplast matK sequences from the connected root tissues. The results showed
      that B. japonica parasitizes on Symplocos species, and that B. yakushimensis
      parasitizes on Distylium racemosum in Japan and Schima superba in Taiwan's
      population.

PMID- 21894575
TI  - Transient global amnesia: a brief review and update.
AB  - Transient global amnesia (TGA) is a transitory syndrome of memory loss, lasting
      less than 24 h. Although there are many known causes of transient amnesia, the
      syndrome of TGA remains of unknown etiology. Known causes of transient amnesia,
      theories of pathogenesis of TGA, and recommended evaluation and treatment are
      discussed.

PMID- 21894576
TI  - Belief in luck or in skill: which locks people into gambling?
AB  - According to the social axioms framework, people's beliefs about how the world
      functions (i.e., internal or external locus of control) are related to their
      social behaviors. Previous researchers have attempted to relate locus of control
      to gambling behavior, but the results have not been clear-cut. The present study
      speculated that the effects of perceived control (i.e., belief in luck and belief
      in skill) on gambling behavior are domain-specific and vary with the type of
      gambling. A total of 306 adult Macau residents ranging in age from 18 to 65 with
      casino gambling experience were recruited by going door to door. Empirical data
      on gambling frequency and perceived control relating to 13 types of gambling were
      collected. Our results demonstrated that the effects of belief in luck or skill
      on gambling behavior varied across different gambling categories. Specifically,
      for football lottery, Chinese lottery, and baccarat, it was not belief in skill
      but rather belief in luck that was a positive significant predictor of gambling
      frequency. Only for slot machines and stud poker did belief in skill
      significantly predict gambling frequency. For the remaining eight gambling
      categories, neither belief in luck nor belief in skill could predict gambling
      frequency. Our findings indicate that neither internal nor external locus of
      control can consistently explain people's gambling behaviors. Instead, which
      factor plays a greater role in a person's gambling behavior is dependent on the
      gambling type. Therefore, the finding that not all gambles are created equal
      might be a promising avenue for further research and treatment approaches.

PMID- 21894577
TI  - Gastric cancer treatment in Japan: 2008 annual report of the JGCA nationwide
      registry.
AB  - The Japanese Gastric Cancer Association (JGCA) started a new nationwide gastric
      cancer registry in 2008. Approximately 50 data items, including surgical
      procedures, pathological diagnoses, and survival outcomes, for 12004 patients
      with primary gastric cancer treated in 2001 were collected retrospectively from
      187 participating hospitals. Data were entered into the JGCA database according
      to the JGCA Classification of gastric carcinoma, 13th edition and the
      International Union Against Cancer (UICC) TNM Classification of malignant tumors,
      5th edition by using an electronic data collecting system. Finally, data of 11261
      patients with gastric resection were analyzed. The 5-year follow-up rate was
      83.5%. The direct death rate was 0.6%. TNM 5-year survival rates (5YSRs)/JGCA
      5YSRs were 91.8/91.9% for stage IA, 84.6/85.1% for stage IB, 70.5/73.1% for stage
      II, 46.6/51.0% for stage IIIA, 29.9/33.4% for stage IIIB, and 16.6/15.8% for
      stage IV. The proportion of patients more than 80 years old was 7.0%, and their
      5YSR was 48.7%. Compared to the JGCA archived data, though the follow-up rate
      needs to be improved, these data suggest that the postoperative results of
      patients with primary gastric carcinoma have improved in those with advanced
      disease and in the aged population in Japan.

PMID- 21894578
TI  - [Technical orthopedics and orthopedic shoe technique].

PMID- 21894582
TI  - Abstracts of the 8th International Sphingolipid Club Meeting. June 30-July 2,
      2010. Glasgow, United Kingdom.

PMID- 21894583
TI  - Fullerenes, carbon nanotubes, and graphene for molecular electronics.
AB  - With the constant growing complexity of electronic devices, the top-down approach
      used with silicon based technology is facing both technological and physical
      challenges. Carbon based nanomaterials are good candidates to be used in the
      construction of electronic circuitry using a bottom-up approach, because they
      have semiconductor properties and dimensions within the required physical limit
      to establish electrical connections. The unique electronic properties of
      fullerenes for example, have allowed the construction of molecular rectifiers and
      transistors that can operate with more than two logical states. Carbon nanotubes
      have shown their potential to be used in the construction of molecular wires and
      FET transistors that can operate in the THz frequency range. On the other hand,
      graphene is not only the most promising material for replacing ITO in the
      construction of transparent electrodes but it has also shown quantum Hall effect
      and conductance properties that depend on the edges or chemical doping. The
      purpose of this review is to present recent developments on the utilization
      carbon nanomaterials in molecular electronics.

PMID- 21894584
TI  - The reasonable calculation of complete enteroscopy rate for balloon-assisted
      enteroscopy.

PMID- 21894587
TI  - [Prevention of ventilator-associated pneumonia: what's evidence-based
      treatment?].
AB  - Patients who suffer from a ventilator-associated pneumonia (VAP) are ventilated
      longer, stay longer in the ICU and in hospital and therefore lead to higher
      costs. Despite the therapeutic potential of the VAP nowadays there is about 10%
      additional mortality observed. Although the clinical VAP diagnosis is limited
      (sensitivity/specificity) rapid diagnosis promotes treatment (calculated
      antibiotic therapy) and improves the survival rate. And in the course the review
      of the VAP diagnosis of unnecessary antibiotics reduces the resistance
      development in that area and also the selection pressure.

PMID- 21894588
TI  - [ICU delirium: Consequences for management of analgesia and sedation in the
      critically ill].
AB  - Monitoring and protocolized management for analgesia, sedation and delirium are
      key indicators for an evidence-based treatment of critically ill patients.
      Through the dissemination of these guidelines in 2006, use of monitoring was
      shown to have improved from 8 to 51% and the use of protocol-based approaches
      increased to 46% (from 21%). From 2006-2009, the existing guidelines from the
      DGAI (Deutsche Gesellschaft fur Anasthesiologie und Intensivmedizin) and DIVI
      (Deutsche Interdisziplinare Vereinigung fur Intensiv- und Notfallmedizin) were
      developed into 3rd Generation Guidelines for the securing and optimization of
      quality of analgesia, sedation and delirium management in the intensive care unit
      (ICU). In collaboration with another 10 professional societies, the literature
      has been reviewed using the criteria of the Oxford Center of Evidence Based
      Medicine. Using data from 671 reference works, text, diagrams and recommendations
      were drawn up. The new 3rd Generation Guideline now includes evidence and
      consensus-based recommendations for the management of delirium in the intensive
      care unit.

PMID- 21894589
TI  - [Malaria in anaesthesia and critical care].

PMID- 21894590
TI  - [Hygiene specialists].
AB  - In 2009 the Commission for Hospital Hygiene and Prevention of Infections (CHHPI)
      at the Robert Koch Institute (RKI) published recommendations on the personnel and
      organisational prerequisites for the prevention of nosocomial infections.
      Emphasis was placed on the tasks of all members of professional groups who belong
      to or work closely with a team of hygiene specialists in an institution for
      outpatient or inpatient medical care. Since these recommendations have not yet
      been adequately implemented and because of the repeated occurrence of hygiene
      deficits in the health-care services the legislature has been forced to pass a
      new law on hospital hygiene. This law requires the managers of hospitals and
      other medical facilities to avoid nosocomial infections and to abide by the
      recommendations of CHHPI and RKI. The already existing shortage of hygiene
      specialists, and especially of hospital hygiene specialists, is thereby further
      intensified. Thus there are initiatives to provide physicians working in
      hospitals with further training in hygiene so that they can take over the
      functions of a hospital hygiene specialist.

PMID- 21894591
TI  - [Airway management in the 21st century--old problems without solutions?].

PMID- 21894592
TI  - [Airwaymanagement: video-assisted airway management].
AB  - Endotracheal intubation remains the "goldstandard" in airway management. If with
      use of conventional techniques intubation of the patient fails, or if an
      anticipated difficult airway is present, video-assisted techniques may help to
      increase intubation success. Video-assisted techniques give the possibility to
      indirectly visualise the laryngeal structures with fibreoptical or camerachip
      technique, and to display the videopicture on an external or integrated monitor.
      For the anticipated difficult airway, awake flexible fibreoptical intubation
      still is the first choice. However, if Oxygenation and Ventilation can be
      established with bag-mask ventilation or supraglottic airways, the use of an
      endoscopic optical stylet or a videolaryngoscope may be alternatives. If the
      algorithm for the unanticipated difficult airway can be safely administered, the
      latter techniques may also be used as emergency intubation devices.

PMID- 21894593
TI  - [Supraglottic airway devices].
AB  - Supraglottic airway devices are developed with increasing frequency following the
      overwhelming success of the laryngeal mask airway (LMA). In contrast to the first
      generation devices such as the 'classic' LMA and the laryngeal tube second
      generation devices usually offer an oesophageal drainage tube and/or an improved
      oropharyngeal leak pressure during positive pressure ventilation such as the
      laryngeal mask ProSeal and the laryngeal tube S. Recently the disposable versions
      of these supraglottic airway devices and the novel I-Gel mask have gained
      increasing interest. Both the LMA and the PLMA have been shown to be perfectly
      suitable for routine anaesthesia and emergency airway management. While the
      lacking protection against aspiration is still considered a major limitation of
      the LMA, the value of airway devices with an oesophageal drainage tube in this
      respect remains untermined at present.

PMID- 21894594
TI  - [Invasive airway management update 2011].
AB  - Invasive airway management techniques are still challenging even for skilled
      anesthesiologists, intensivists and emergency physicians. All current
      percutaneous tracheostomy techniques are based on Seldinger's principle. Using
      the recent introduced Blue Dolphin Kit is feasible and safe, but without clear
      advantage compared to other kits. There is no data available to generally support
      performing early (<8 days) tracheostomy in intensive care patients requiring
      mechanical ventilation. Experimental data show promising results of supporting
      expiration through a small bore catheter using ejectors based on Bernoulli's
      principle in terms of minimizing risk of barotrauma during emergency
      transtracheal high frequency jet ventilation.

PMID- 21894595
TI  - [Experience in practice. The use of modern media in pediatric anesthesia].

PMID- 21894596
TI  - Treatment of chronic occlusions of the iliac or femoropopliteal arteries with
      mechanical rotational catheters.
AB  - PURPOSE: The main problem with treating chronic lesions with percutaneous
      transluminal angioplasty (PTA) or stent implantation is the relatively high
      restenosis rate. The objective of this prospective single-center study was to
      evaluate a mechanical rotational catheter (Straub Rotarex(r)) for its safety and
      efficacy in the treatment of chronic vascular occlusions. MATERIALS AND METHODS:
      There were 40 patients with a mean age of 67.3 +/- 7.6 years (51 - 86) treated by
      means of the Rotarex(r) catheter. All patients had chronic occlusions (> 6
      months) of the iliac (n = 4) or femoropopliteal arteries (n = 36). The
      preinterventional Rutherford stage was on average 3.15 (2 - 5). The mean lesion
      length was 12.3 cm (2 - 24 cm). The ankle-brachial index (ABI) was determined
      prior to and after the intervention, as well as after 12 months. An additional
      follow-up was performed using color-coded duplex sonography. RESULTS: The
      technical success rate was 100 %. In 27 patients (67.5 %), adjunctive balloon
      dilation was performed, and 7 (17.5 %) patients required a stent implantation.
      Clinically, there was an increase in the ankle-brachial index from 0.57 +/- 0.15
      to 0.82 +/- 0.16 post-interventionally. After 12 months, it was 0.80 +/- 0.12,
      and the average Rutherford stage fell to 1.65 (1 - 3). During the follow-up
      observation period, there were 9 (22.5 %) restenoses. Two dissections after
      balloon dilatation were recorded as peri-interventional complications. No distal
      embolizations were observed. There were no amputations or deaths during the
      entire period of the study. CONCLUSION: The atherectomy of lesions of the iliac
      and femoropopliteal arteries using the Rotarex(r) system is safe and effective.
      The low rate of peri-interventional stenting and the low rate of restenosis at 12
      months appear to be promising.

PMID- 21894597
TI  - [Treatment of in-stent reocclusions of femoropopliteal arteries with mechanical
      rotational catheters].
AB  - PURPOSE: The main problem with the treatment of arterial stenoses by percutaneous
      transluminal angioplasty (PTA) or stent implantation is the relatively high
      restenosis rate. The objective of this prospective single-center study was to
      evaluate a mechanical rotational catheter (Straub Rotarex(r)) for its safety and
      efficacy in the treatment of in-stent reocclusions. MATERIALS AND METHODS: 78
      patients with a mean age of 64.2 +/- 8.3 years (42 - 85) were treated by means of
      the Rotarex(r) catheter. All patients had in-stent reocclusions of the
      femoropopliteal arteries. The preinterventional Rutherford stage was on average
      3.36 (2 - 5). The mean lesion length was 14.7 cm (6 - 30 cm). The ankle-brachial
      index (ABI) was determined prior to and after the intervention, as well as after
      12 months. An additional follow-up was performed using color-coded duplex
      sonography. RESULTS: The technical success rate was 97.4 % (76 / 78). In 52 / 76
      patients (68.4 %), adjunctive balloon dilation was performed, and 8 / 76 (10.5 %)
      patients required a stent implantation. Clinically, there was an increase in the
      ankle-brachial index from 0.61 +/- 0.17 to 0.85 +/- 0.15 post-interventionally.
      After 12 months, it was 0.78 +/- 0.16, and the average Rutherford stage fell to
      1.65 (1 - 3). During the follow-up observation period, there were 14 (18.4 %)
      restenoses. Two dissections after Rotarex were recorded as peri-interventional
      complications. No distal embolizations were observed. There were no amputations
      or deaths during the entire period of the study. CONCLUSION: The recanalization
      of in-stent reocclusions of femoropopliteal arteries using the Rotarex(r) system
      is safe and effective. The low rate of restenosis at 12 months appears to be
      promising.

PMID- 21894598
TI  - [Case report: an observation of free air in the breast].

PMID- 21894599
TI  - Contrast-enhanced ultrasonography for the detection of joint vascularity in
      arthritis--subjective grading versus computer-aided objective quantification.
AB  - PURPOSE: To compare joint inflammation assessment using subjective grading of
      power Doppler ultrasonography (PDUS) and contrast-enhanced ultrasonography (CEUS)
      versus computer-aided objective CEUS quantification. MATERIALS AND METHODS: 37
      joints of 28 patients with arthritis of different etiologies underwent B-mode
      ultrasonography, PDUS, and CEUS using a second-generation contrast agent.
      Synovial thickness, extent of vascularized pannus and intensity of
      vascularization were included in a 4-point PDUS and CEUS grading system.
      Subjective CEUS and PDUS scores were compared to computer-aided objective CEUS
      quantification using Qontrast(r) software for the calculation of the signal
      intensity (SI) and the ratio of SI for contrast enhancement. RESULTS: The
      interobserver agreement for subjective scoring was good to excellent (kappa = 0.8
      - 1.0; P < 0.0001). Computer-aided objective CEUS quantification correlated
      statistically significantly with subjective CEUS (P < 0.001) and PDUS grading (P
      < 0.05). The Qontrast(r) SI ratio correlated with subjective CEUS (P < 0.02) and
      PDUS grading (P < 0.03). Clinical activity did not correlate with vascularity or
      synovial thickening (P = N. S.) and no correlation between synovial thickening
      and vascularity extent could be found, neither using PDUS nor CEUS (P = N. S.).
      CONCLUSION: Both subjective CEUS grading and objective CEUS quantification are
      valuable for assessing joint vascularity in arthritis and computer-aided CEUS
      quantification may be a suitable objective tool for therapy follow-up in
      arthritis.

PMID- 21894600
TI  - Quality indicators for the development and didactics of ultrasound courses in
      continuing medical education.
AB  - PURPOSE: Based on evaluation data from participant feedback, a concept was to be
      developed for introductory abdominal ultrasound courses lasting several days.
      This approach was to be developed incrementally with the intent of maximizing the
      learning effect per time. MATERIALS AND METHODS: This concept has been modified
      annually over several years based on the findings of educational research and the
      scores on final examinations in OSCE format. It has been modified with the aid of
      detailed questionnaires completed by approximately 2000 participating physicians
      and has thus undergone incremental optimization. RESULTS: Analysis of the most
      recent 1005 questionnaires has shown that participants recommend a modular course
      design with only brief lectures on theory (average optimal duration of 20 min.,
      SD 9.6 min.). These should alternate with longer practical "hands-on" ultrasound
      exercises (60 - 90 min., accounting for at least 50 - 60 % of the course time),
      consolidating drawing exercises, and breaks. 51 % of the physicians specified 5
      participants as the ideal group size for practical exercises, while 43 %
      specified only 4. The discussion presents 10 specific quality indicators for
      efficient ultrasound courses. It elucidates the feasibility and logistical
      prerequisites of this model, and compares it with other basic course concepts.
      Furthermore, this article presents a model for an evaluation covering the course
      concept and tutors as well as discussing a training program for tutors including
      a cost analysis. CONCLUSION: In summary, the participants estimate the course
      design to represent a mature concept that has demonstrated its feasibility and
      broad acceptance among physicians in CME.

PMID- 21894601
TI  - Letter to the editor: Ewertsen et al. Characterization by biopsy or CEUS of liver
      lesions guided by image fusion between ultrasonography and CT, PET/CT or MRI.

PMID- 21894602
TI  - Three cases of stroke in patients with atypical presentation of type a aortic
      dissection--potential of neurosonography in the early diagnosis of atypical
      stroke.

PMID- 21894603
TI  - [Profile of neurovascular emergencies in a tertiary care hospital: evolution over
      the period 2001-2008].
AB  - INTRODUCTION: Acute cerebrovascular disease, or stroke, is one of the most
      prevalent pathologies in Europe and is a very common reason for visits to the
      emergency services of a tertiary care hospital. AIM. To explore the types of
      emergency neurovascular pathology that are treated at the hospital and their
      development and impact over an eight-year period. PATIENTS AND METHODS: The
      prospective study included 11,254 consecutive patients with acute stroke. The
      following variables were reported: demographic data, type of stroke, first
      stroke, need for hospital admission, fibrinolysis, mean stay and mortality rate.
      RESULTS: Between January 2001 and December 2008, an average of four patients were
      treated per day, with a predominance of males (53.6%) and a mean age of 71.8 +/-
      13.8 years, which was five years higher in females (p < 0.001). Ischaemic stroke
      represented 84.6% of the total number and haemorrhagic stroke accounted for the
      remaining 15.4%. Throughout the eight years of the study, there was seen to be an
      increase in the number of non-lacunar strokes (44-49%; p < 0.05), intracerebral
      haemorrhage (13.7-16.4%; not significant), first stroke (63.5-74.6%; p < 0.05)
      and fibrinolysis (6.2-13.5%; p < 0.001). The number of strokes in young patients
      increased (47.5%), at the expense of ischaemic stroke (p = 0.002) and males (p =
      0.023). In contrast, there was a decrease in the number of transient ischaemic
      attacks (18.9-11.9%; p < 0.05), the need to be admitted to hospital (56-49.3%; p
      < 0.05), mean length of stay and mortality. CONCLUSIONS: Advances in the
      management of stroke in recent years are associated to a decrease in the need for
      admission to hospital, mortality, and mean length of stay in hospital, together
      with a change in the clinical profile of the patients treated in emergency
      departments. The increase in the number of cases of strokes among young people is
      something that health care systems should take note of.

PMID- 21894604
TI  - [Differential effects of dual tasks on emotional processing in non-medicated
      patients with Parkinson's disease].
AB  - INTRODUCTION: Previous research has shown that correct identification of
      emotional facial expressions (EFE) depends on the cognitive resources that are
      available. In this study, we examine whether the capacity to identify EFE in a
      dual task paradigm is affected in Parkinson's disease (PD). AIM: To investigate
      the interference generated by introducing a secondary task in EFE processing
      during the encoding and recovery of the facial expression in non-medicated PD
      patients. SUBJECTS AND METHODS: A total of 14 patients with de novo PD and 28
      healthy adults identified 24 EFE under two conditions: simultaneous encoding
      along with a secondary task and introduction of the secondary task between the
      time that spans the encoding of the primary task and the response time latency.
      RESULTS: Results showed that identification of EFE by patients with PD was
      significantly worse than by healthy adults in the simultaneous encoding
      condition. In contrast, no differences were found when the interference of the
      secondary task took place in the phase involving recovery of information of the
      primary task. CONCLUSIONS: Patients with PD only display specific deficits in
      processing EFE when the task consumes high levels of the resources required for
      divided attention, as occurs in everyday situations.

PMID- 21894605
TI  - [A critical analysis of neuroimaging studies in relation to cognitive performance
      in multiple sclerosis patients].
AB  - Studying the cognitive impairment of multiple sclerosis (MS) patients is
      fundamental for a global understanding of this disease. Neuroimaging techniques
      might provide crucial data about the nature of this deficit and their
      progression. Accordingly to this idea, over the last years there has been a
      marked increase in the number of studies devoted to explore the possible
      relationship between the cognitive alterations of this clinical population and
      different sorts of neuropathological indexes provided by both, classical as well
      as by more recently developed techniques. The results of the studies using
      structural information provided by structural techniques, have revealed the
      important role of atrophic processes in the aethiology of cognitive decline in MS
      patients. However, this information needs to be complemented with newer indexes
      of neuropathological alterations in 'apparently normal' gray and white matter. On
      the other hand, functional magnetic resonance imaging studies have provided clear
      evidence of the existence and functional significance of neuroplastic processes
      that can mask the relationship between morphological markers of tissue damage and
      cognitive performance of MS patients. Those neuroplastic processes need to be
      taken into account as they might compensate the cognitive decline of this
      clinical population. In summary, the present review tries to provide a critic and
      integrative view of different studies assessing the relationship between
      cognitive impairment in MS patients and different kinds of information provided
      by neuroimaging techniques.

PMID- 21894606
TI  - [Brachial arterial flow mediated dilation: utility in clinical and experimental
      practice].
AB  - Brachial artery flow mediated dilation (FMD) is a validated, noninvasive
      physiological measure widely used as a research tool to quantify endothelial
      function. FMD is diminished in patients with several coronary risk factors,
      coronary artery disease, peripheral arterial disease, stroke, and is an
      independent predictor of cardiovascular events. FMD represents a useful method
      for identify asymptomatic atherosclerotic subjects with raised risk of developing
      atherothrombotic complications and improves with risk-reduction therapy such as
      antihypertensive or antidiabetic drugs, antiplatelet agents and statins. FMD
      could be a great usefulness in ischemic stroke such as stroke subtypes
      classification, prognostic significance in acute phase, and independent predictor
      for new-onset vascular event after first-ever stroke, but also in other disease
      such as cerebral haemorrhage, migraine or syncope. In this review article,
      brachial artery FMD and its role in experimental and clinical practice is
      extensively discussed.

PMID- 21894607
TI  - [White matter in developmental disorders].
AB  - The white matter is the main connection between different regions of the brain
      and helps them to work in a unified, coordinated way. Diffusion tensor imaging is
      an ideal technique with which to study it in order to detect the degree of
      integrity of these fibres. Nowadays, they are considered to play a significant
      role in the development and pathophysiology of different developmental disorders,
      and the aim of this study was to examine this role. On reviewing disorders such
      as autism, dyslexia or attention deficit hyperactivity disorder, certain fibres
      were found to be clearly involved. This was especially the case of the (arcuate)
      superior longitudinal fasciculus and the temporal-parietal network (related with
      the regulation of motor and attentional behaviour), the corpus callosum (which
      ensures the efficient and swift exchange of information between the hemispheres
      of the brain) and cingulate regions (which would be related with social cognition
      and self-consciousness).

PMID- 21894609
TI  - [Natural history of spontaneous bilateral carotid dissection with four associated
      pseudoaneurysms].

PMID- 21894610
TI  - [Numb chin syndrome secondary to an osteoblastic osteosarcoma].

PMID- 21894611
TI  - [Long live neuropsychology!].

PMID- 21894612
TI  - Chinese Clinical Trial Registry: mission, responsibility and operation.
AB  - As a national public clinical trial registry and a recognized Primary Registry of
      the WHO ICTRP, the Chinese Clinical Trial Registry (ChiCTR) has responsibility to
      disseminate knowledge about clinical trial transparency, which is an important
      ethical issue for healthcare studies involving humans, and to promote the quality
      of healthcare studies in China. This article describes the mission, policy and
      operation of the ChiCTR. We discuss the need to improve the quality of clinical
      trials and our ideas for new developments. The registration of clinical trials is
      an ethical responsibility and obligation for researchers. A clinical study is a
      public event itself, which needs the participation of the public, and its results
      should also be seen as a service to the public. Therefore, the public have the
      right to know how a study is progressing.

PMID- 21894613
TI  - The ISRCTN Register: achievements and challenges 8 years on.
AB  - The ISRCTN register has been operational for the past 8 years and is approaching
      10,000 trial records. It complies with international guidelines and pools its
      data in the International Trial Search Portal initiated by the World Health
      Organisation. Through its ongoing collaboration with the Department of Health in
      England, the register has been able to participate in a national initiative
      aiming to bring clinical trials to the attention of a wider public with the
      objective of maximising participation. As part of BioMed Central, the register
      provides the first step in the concept of threaded publications, enabling the
      tracking of clinical research studies from inception and the linking of all
      resulting publications including the raw data where this is available.

PMID- 21894614
TI  - Growing everyday: the Pan African Clinical Trials Registry.
AB  - The Pan African Clinical Trial Registry (http://www.pactr.org), established as
      the AIDS, Tuberculosis and Malaria Registry (ATM) has developed into the registry
      of choice for African trials. The register was formally launched as a World
      Health Organization primary register in September 2009. Data analysis shows that
      registry applications have increased steadily since then, as has representation
      throughout the region. New developments to the registry include the
      implementation of a real-time Global Information Systems map on the portal and
      development of Standard Operating Procedures while focused efforts on
      dissemination continue. http://www.pactr.org is now well-placed to provide a
      valuable resource for researchers, clinicians, policy-makers and consumers on the
      continent.

PMID- 21894615
TI  - The Cuban Public Registry of Clinical Trials: primary registry of World Health
      Organization.
AB  - Despite the importance of randomized trials for well-informed decisions in health
      care, a large proportion of the results of these trials are not published,
      especially when they are negative. Publication bias has a negative impact in the
      treatment of patients, due to the distorted impression it leads to for new
      therapies. Clinical Trial Registries help to overcome this by providing
      transparency in the process of conducting research. The World Health Organization
      takes the position that the registration of interventional trials is a
      scientific, ethical and moral responsibility. Taking account of this global
      movement, the National Coordinating Centre of Clinical Trials and the Cuban
      Health Network, designed and implemented the Cuban Public Registry of Clinical
      Trials. The Registry was established in June 2007 and is intended for public
      service in Cuban territory, although it is open to registrants and patients
      outside Cuba. The Registry staff developed a strategy to become a Primary
      Registry of the World Health Organization, and this was achieved in February
      2011.

PMID- 21894616
TI  - The Sri Lanka Clinical Trials Registry--moving forward.
AB  - The Sri Lanka Clinical Trials Registry (SLCTR) is a Primary Registry in the
      Registry Network of the World Health Organization's International Clinical Trials
      Registry Platform (WHO-ICTRP), and regularly feeds data to its Clinical Trials
      Search Portal. Over the last few years, the SLCTR has been able to achieve its
      original objective of providing a national trial register for Sri Lankan
      researchers, but its role has always been more than that of a mere storehouse of
      trial data. The research landscape is rapidly changing in Sri Lanka, and the
      SLCTR has been a key stimulus to a resurgent interest in clinical research among
      the Sri Lankan research community. The SLCTR is working together with its partner
      stakeholders to facilitate research in the country, and to ensure that clinical
      trials conducted in Sri Lanka meet the highest ethical and scientific standards.

PMID- 21894617
TI  - Smoke and mirrors. By Caveman.

PMID- 21894618
TI  - The Golden State of healthcare reform: ethnoeconomic origins of outcome
      imbalance.

PMID- 21894619
TI  - Inclusive trauma systems must embody appropriate triage guidelines.

PMID- 21894620
TI  - Life, liberty, and the pursuit of HAIs.

PMID- 21894621
TI  - To band or to bypass, that is the question.

PMID- 21894622
TI  - Just as the twig is bent, the tree's inclined: lessons from the future of
      surgical education.

PMID- 21894623
TI  - Just because you can doesn't mean you should...because many of us really can't!

PMID- 21894624
TI  - Great statistics and the real world.

PMID- 21894625
TI  - Colloidal synthesis of ultrathin two-dimensional semiconductor nanocrystals.
AB  - 2D semiconductor quantum wells have been recognized as potential candidates for
      various quantum devices. In quantum wells, electrons and holes are spatially
      confined within a finite thickness and freely move in 2D space. Much effort has
      focused on shape control of colloidal semiconductor nanocrystals(NCs), and
      synthesis of 2D colloidal NCs has been achieved very recently. Here, recent
      advances in colloidal synthesis of uniform and ultrathin 2D CdSeNCs are
      highlighted. Structural and optical property characterization of these quantum
      sized 2D CdSe NCs is discussed. Additionally, 2D CdSe NCs doped with Mn 2+ ions
      for dilute magnetic semiconductors (DMS) are presented.These 2D CdSe-based NCs
      can be used as model systems for studying quantum-well structures.

PMID- 21894626
TI  - What is the value of professional opinion? Comment.

PMID- 21894627
TI  - Paraphenylene diamine poisoning.

PMID- 21894628
TI  - Florida: Second thoughts.

PMID- 21894630
TI  - Multi-household farming system in a northeastern Thai village: its transformation
      during economic development.
AB  - Farming households with close kinship ties in northeast Thailand have long been
      practising joint utilization of farmland. They used this multihousehold farming
      method even more actively to cope with the macroeconomic development beginning in
      the 1960s. A 1989 survey of a village by the author found more than one-third of
      farmland under such communal use. However, the share decreased drastically by
      2000, Economic growth has reached a point where farmers have to discard the
      communal system and introduce a market system of land utilization, such as
      sharecropping even between households of close kin.

PMID- 21894629
TI  - When push comes to shove: sites of vulnerability, personal transformation, and
      trafficked women's migration decisions.
AB  - Discussions of the push and pull factors behind trafficked women's decisions to
      migrate abroad for tenuous work opportunities in the "entertainment" sector tend
      to variously privilege poverty, familial obligations, and, more recently,
      personal opportunism. This reinforces more general observations about motivations
      for "Third World" women who migrate to more developed regions globally. Although
      these factors are indeed important, the author's research has revealed the
      relevance of other explanations for migration decisions, including the prevalence
      of domestic violence, family dissolution, and escape from personal circumstances,
      which are themselves products of low self-esteem and sense of self-worth.

PMID- 21894631
TI  - A game of three monkeys: Kadazan Dusun villagers and violence against women.
AB  - Based on detailed and long-term anthropological research among rural Kadazans,
      the paper sets out the social history of domestic violence in one Sabah village.
      In more than 30 per cent of the households, there is a woman who has experienced
      repeated spousal abuse during her life. Adding those men who abused earlier
      spouses, and adults who lived through the abuse of their mothers in childhood, it
      is clear that violence is and has long been part of everyday - yet secret -
      village experience. For various reasons, researchers appear to have colluded in
      ignoring the issue. To help those women and their children whose lives are
      blighted by fear and fearful memories, it would be wise to assume domestic
      violence is as present in rural as in urban settings.

PMID- 21894632
TI  - The socio-economic impacts of rice policies implementation in rural
      Burma/Myanmar.
AB  - This paper, focusing on two rice-farming villages where the Burmese government
      has experimented with a variety of agricultural programmes, explores the problems
      associated with rice implementation processes. In particular it looks at the
      basic structure and operation of agricultural administration - salary and income
      of government officials, the predominance of military officers in civilian
      ministries and departments, the creation of departments with overlapping
      responsibilities, and the hierarchical structure of the Agricultural Ministry -
      and highlight their limitations. It provides another aspect to evaluating the
      roots of poverty among average rice farmers.

PMID- 21894635
TI  - "Not intended to dispossess females": Southern women and Civil War amnesty.

PMID- 21894636
TI  - The cyclic nucleotides.

PMID- 21894637
TI  - Using a trauma-informed framework to care for incarcerated women.
AB  - Available health and social services in women's correctional facilities often do
      not consider the interrelationship of gender, trauma, and mental illness. As a
      result, preexisting health issues are often exacerbated, leaving women to reenter
      their communities with more complex health needs. We propose that a trauma
      informed framework can be used to guide clinical interactions with female
      inmates. A case study is presented as an example of proposed best clinical
      practice. Future trauma-related practice implications are provided.

PMID- 21894638
TI  - Adrenergic receptors. Preface.

PMID- 21894639
TI  - Cell boundary and intracellular space. Preface.

PMID- 21894640
TI  - Klaus Kurtenbach--a tribute to his life.

PMID- 21894641
TI  - Structural characteristics correlate with immune responses induced by HIV
      envelope glycoprotein vaccines.
AB  - HIV envelope glycoprotein (Env) is the target for inducing neutralizing
      antibodies. Env is present on the virus surface as a trimer, and, upon binding to
      CD4, a cascade of events leads to structural rearrangement exposing the co
      receptor binding site and entry into the CD4+ host target cells. We have designed
      monomeric and trimeric Env constructs with and without deletion of the variable
      loop 2 (DeltaV2) from SF162, a subtype B primary isolate, and performed
      biophysical, biochemical and immunological studies to establish a potential
      structure-functional relationship. We expressed these Envs in CHO cells, purified
      the proteins to homogeneity and performed biophysical studies to define the
      binding properties to CD4, structural characteristics and exposure of epitopes
      recognized by b12 and CD4i mAb (17B) on both full-length and mutant HIV Env
      proteins. Parameters evaluated include oligomerization state, number and affinity
      of CD4 binding sites, enthalpy and entropy of the Env-CD4 interaction and
      affinity for b12 and 17b mAbs. We observed one CD4 binding site per monomer and
      three active CD4 binding sites per trimer. A40-fold difference in affinity of the
      gp120 monomer vs. the o-gp140 trimer towards CD4 was observed (Kd = 58 nM and 1.5
      nM, respectively),whereas only a 2-fold difference was observed for the V2
      deleted Envs (Kd of gp120DeltaV2 = 19 nM, Kd of o-gp140DV2 = 9.3 nM). Monomers
      had 3-fold higher affinity to the mAb 17b and at least 3-fold weaker affinity to
      b12 compared to trimers, with gp120DV2 having the weakest affinity for b12 (Kd =
      446 nM). Affinity of CD4 binding correlated with proportion of the antibodies
      induced against the conformational epitopes by the corresponding Envs, and
      changes in mAb binding correlated with the induction of antibodies directed
      against linear epitopes. Furthermore,biophysical analysis reveals that the V2
      deletion has broad structural implications in the monomer not shared by the
      trimer, and these changes are reflected in the quality of the immune responses
      induced in rabbits. These data suggest that biophysical characteristics of HIV
      Env, such as affinity for CD4, and exposure of important neutralizing epitopes,
      such as those recognized by b12 mAb, may be important predictors of its in vivo
      efficacy and may serve as important surrogate markers for screening Env
      structures as potential vaccine candidates.

PMID- 21894642
TI  - [Ethical dilemmas in the medical practice in 2010: reflexions around the results
      of a survey to 10,000 physicians].

PMID- 21894643
TI  - General Halleck's itchy elbows.
AB  - General Henry Wager Halleck served as general-in-chief and chief of staff of the
      Federal army from 1862-1865. Unpopular with troops as well as with many members
      of the Lincoln administration, he was a particular source of irritation to
      Secretary of Navy Gideon Welles. In his posthumously-published diary of the war
      years, Welles viciously criticized Halleck for his failings as army commander.
      Welles also derided Halleck's personality and personal appearance. Welles found
      the general's habitual elbow-scratching annoying enough to mention it in five
      separate diary entries. This depiction of Halleck ceaselessly, nervously
      scratching his elbows has entered Civil War folklore. Why did Halleck scratch his
      elbows? Two possibilities exist. Either he did so compulsively, as a nervous
      habit, or he was scratching an itch. In this paper, I present a speculative
      argument that Halleck may have had a skin disease, possibly atopic dermatitis,
      and that this may have contributed to or have been the sole cause of his elbow
      scratching.

PMID- 21894644
TI  - Life of a contract surgeon.

PMID- 21894645
TI  - The eye disease of Jefferson Davis (1808-1889).
AB  - The only Confederate president, Jefferson Davis, led a long and eventful life. He
      was a Mississippi planter, a husband, a father, West Point graduate, war hero,
      congressman, senator, secretary of war, and finally President of the Confederate
      States of America. In many ways he was a study of contrast with his northern
      counterpart Abraham Lincoln. Davis was personally courageous and a rich,
      educated, southern aristocrat who did not deeply understand the political process
      or have the refined personal skills necessary to work well with others. Prior to
      his Presidency he served with distinction in two wars, but as a result of his
      confederate activity and pro-slavery philosophy he is one of the least discussed
      famous Americans. Davis's health was a constant problem and he suffered an almost
      fatal attack of 'malaria' in 1836. In the winter of 1857-1858, he again was
      seriously ill and by the end of February 1858, a chronic, relapsing, ocular
      inflammatory condition began. Using historical evidence from multiple sources,
      this paper will propose a diagnosis of the Confederate President's ocular
      condition and consider how this could have influenced his military and political
      decisions.

PMID- 21894647
TI  - The "Building Parson": the role of Reverend David Hall in the solution of
      Ireland's early twentieth-century housing problems.

PMID- 21894648
TI  - Medicare program; hospital inpatient prospective payment systems for acute care
      hospitals and the long-term care hospital prospective payment system and FY 2012
      rates; hospitals' FTE resident caps for graduate medical education payment. Final
      rules.
AB  - We are revising the Medicare hospital inpatient prospective payment systems
      (IPPS) for operating and capital-related costs of acute care hospitals to
      implement changes arising from our continuing experience with these systems and
      to implement certain statutory provisions contained in the Patient Protection and
      Affordable Care Act and the Health Care and Education Reconciliation Act of 2010
      (collectively known as the Affordable Care Act) and other legislation. We also
      are setting forth the update to the rate-of-increase limits for certain hospitals
      excluded from the IPPS that are paid on a reasonable cost basis subject to these
      limits. We are updating the payment policy and the annual payment rates for the
      Medicare prospective payment system (PPS) for inpatient hospital services
      provided by long-term care hospitals (LTCHs) and implementing certain statutory
      changes made by the Affordable Care Act. In addition, we are finalizing an
      interim final rule with comment period that implements section 203 of the
      Medicare and Medicaid Extenders Act of 2010 relating to the treatment of teaching
      hospitals that are members of the same Medicare graduate medical education
      affiliated groups for the purpose of determining possible full-time equivalent
      (FTE) resident cap reductions.

PMID- 21894646
TI  - Uric acid and xanthine oxidase: future therapeutic targets in the prevention of
      cardiovascular disease?
AB  - Serum uric acid may be an independent risk factor for cardiovascular disease.
      This review examines this association, potential mechanisms, and explores whether
      strategies to reduce uric acid will improve outcomes. The recent studies of
      xanthine oxidase inhibition are given particular focus. Epidemiological evidence
      supports the theory that uric acid is an independent risk factor for
      cardiovascular disease. Recent studies of losartan, atorvastatin and fenofibrate
      suggest that uric acid reduction contributes to the risk reduction offered by
      these therapies. Several small studies of xanthine oxidase inhibition have shown
      improvements in measures of cardiovascular function of a similar magnitude to
      that of other proven preventative treatments. These trial data and the convincing
      epidemiological evidence mandate that large clinical trials of uric acid-lowering
      strategies are performed in patients with or at high risk of cardiovascular
      disease. If such approaches are shown to be effective in reducing cardiovascular
      events, they would represent a novel and cost-effective preventative approach.

PMID- 21894650
TI  - The tiger stirring: aspects of commuting in the Republic of Ireland, 1981-1996.

PMID- 21894651
TI  - Medical devices; ophthalmic devices; classification of the eyelid thermal
      pulsation system. Final rule.
AB  - The Food and Drug Administration (FDA) is classifying the eyelid thermal
      pulsation system into class II (special controls). The Agency is classifying the
      device into class II (special controls) in order to provide a reasonable
      assurance of safety and effectiveness of the device.

PMID- 21894652
TI  - "Troops of largely diseased women": VD, the contagious diseases acts and moral
      policing in late nineteenth-century Ireland.

PMID- 21894653
TI  - Technical revisions to conform to the Caregivers and Veterans Omnibus Health
      Services Act of 2010. Final rule.
AB  - This final rule amends Department of Veterans Affairs (VA) medical regulations to
      incorporate statutory amendments. Certain statutes authorizing VA health care
      benefits were amended by the Caregivers and Veterans Omnibus Health Services Act
      of 2010. The statutory amendments affect enrollment in certain health care
      priority categories and exempt catastrophically disabled veterans from copayment
      requirements.

PMID- 21894654
TI  - Expansion of state home care for parents of a child who died while serving in the
      armed forces. Final rule.
AB  - This document amends Department of Veterans Affairs (VA) regulations concerning
      the payment of per diem to a State for providing nursing home care to eligible
      veterans. The amendments remove a restriction on VA's payment of per diem, which
      required all non-veteran residents of a State home to be spouses of veterans, or
      parents of veterans all of whose children died while serving in the Armed Forces
      of the United States. Under this final rule, non-veteran residents of the State
      home must be spouses of veterans, or parents of veterans any of whose children
      died while serving in the Armed Forces.

PMID- 21894656
TI  - Urban social movements and housing in Hong Kong: from antagonism to guided
      participation.

PMID- 21894657
TI  - Health care for homeless veterans. Final rule.
AB  - This final rule establishes regulations for contracting with community-based
      treatment facilities in the Health Care for Homeless Veterans (HCHV) program of
      the Department of Veterans Affairs (VA). The HCHV program assists certain
      homeless veterans in obtaining treatment from non-VA community-based providers.
      The final rule formalizes VA's policies and procedures in connection with this
      program and clarifies that veterans with substance use disorders may qualify for
      the program.

PMID- 21894658
TI  - International Conference on Harmonisation; Guidance on E2F Development Safety
      Update Report; availability. Notice.
AB  - The Food and Drug Administration (FDA) is announcing the availability of a
      guidance entitled "E2F Development Safety Update Report." The guidance was
      prepared under the auspices of the International Conference on Harmonisation of
      Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH).
      The guidance describes the format, content, and timing of a development safety
      update report (DSUR) for an investigational drug. The DSUR will serve as a common
      standard for periodic reporting on drugs under development (including marketed
      drugs that are under further study) among the ICH regions. The DSUR can be
      submitted in the United States in place of an annual report for an
      investigational new drug application (IND). The harmonized DSUR is intended to
      promote a consistent approach to annual clinical safety reporting among the ICH
      regions and enhance efficiency by reducing the number of reports generated for
      submission to the regulatory authorities.

PMID- 21894659
TI  - Responsibility of applicants for promoting objectivity in research for which
      public health service funding is sought and responsible prospective contractors.
      Final rule.
AB  - This final rule implements changes to the regulations on the Responsibility of
      Applicants for Promoting Objectivity in Research for which Public Health Service
      Funding is Sought and Responsible Prospective Contractors. Since the promulgation
      of the regulations in 1995, biomedical and behavioral research and the resulting
      interactions among government, research Institutions, and the private sector have
      become increasingly complex. This complexity, as well as a need to strengthen
      accountability, led to changes that expand and add transparency to Investigators'
      disclosure of Significant Financial Interests (SFIs), enhance regulatory
      compliance and effective institutional oversight and management of Investigators'
      financial conflicts of interests, as well as increase the Department of Health
      and Human Services' (HHS) compliance oversight.

PMID- 21894660
TI  - Medicare program; Medicare Advantage and prescription drug benefit programs.
      Final rule.
AB  - This final rule finalizes revisions to the regulations governing the Medicare
      Advantage (MA) program (Part C), prescription drug benefit program (Part D) and
      section 1876 cost plans including conforming changes to the MA regulations to
      implement statutory requirements regarding special needs plans (SNPs), private
      fee-for-service plans (PFFS), regional preferred provider organizations (RPPO)
      plans, and Medicare medical savings accounts (MSA) plans, cost-sharing for dual
      eligible enrollees in the MA program and prescription drug pricing, coverage, and
      payment processes in the Part D program, and requirements governing the marketing
      of Part C and Part D plans.

PMID- 21894661
TI  - Medicare program; changes to the electronic prescribing (eRx) incentive program.
      Final rule.
AB  - This final rule modifies the electronic prescribing (eRx) quality measure used
      for certain reporting periods in calendar year (CY) 2011; provides additional
      significant hardship exemption categories for eligible professionals and group
      practices to request an exemption during 2011 for the 2012 eRx payment adjustment
      due to a significant hardship; and extends the deadline for submitting requests
      for consideration for the two significant hardship exemption categories for the
      2012 eRx payment adjustment that were finalized in the CY 2011 Medicare Physician
      Fee Schedule final rule with comment period.

PMID- 21894662
TI  - New factors-new function.

PMID- 21894663
TI  - Rate increase disclosure and review: definitions of "individual market" and
      "small group market." Final rule.
AB  - This final rule amends a May 23, 2011, final rule entitled "Rate Increase
      Disclosure and Review". The final rule provided that, for purposes of rate review
      only, definitions of "individual market" and "small group market" under State
      rate filing laws would govern even if those definitions departed from the
      definitions that otherwise apply under title XXVII of the Public Health Service
      Act (PHS Act). The preamble to the final rule requested comments on whether this
      policy should apply in cases in which State rate filing law definitions of
      "individual market" and "small group market" exclude association insurance
      policies that would be included in these definitions for other purposes under the
      PHS Act. In response to comments, this final rule amends the definitions of
      "individual market" and "small group market" that apply for rate review purposes
      to include coverage sold to individuals and small groups through associations
      even if the State does not include such coverage in its definitions of individual
      and small group market. This final rule also updates standards for health
      insurance issuers regarding disclosure and review of unreasonable premium
      increases under section 2794 of the Public Health Service Act.

PMID- 21894664
TI  - Nursing by numbers.

PMID- 21894665
TI  - Nursing workforce faces decline in numbers on a 'shocking scale'.

PMID- 21894666
TI  - RCN inundated with ideas that could save the NHS millions.

PMID- 21894667
TI  - Trust ends set staffing levels and hands control to ward managers.

PMID- 21894668
TI  - Foreign nurses may shun UK if their right to settle is removed.

PMID- 21894669
TI  - The overseas visitors who leave an outstanding debt behind them.

PMID- 21894670
TI  - Parkinson's care under threat.

PMID- 21894671
TI  - The nature of nurture.
AB  - The issues of research, credibility and regulation are addressed in the first of
      six articles about complementary and alternative therapies.

PMID- 21894672
TI  - Olympic-sized task.
AB  - As medical services manager for the 2012 Olympic and Paralympic Games, nurse Pam
      Venning has a huge task ahead, organising care for athletes, staff and the
      public.

PMID- 21894673
TI  - Pass the message.
AB  - Babies who are born to young mothers, particularly those in disadvantaged groups,
      are more likely to have adverse outcomes, including cot death. A novel scheme is
      attempting to address the problem.

PMID- 21894674
TI  - Non-diabetic hypoglycaemia: causes and pathophysiology.
AB  - Hypoglycaemia has many possible causes, although similar symptoms in each case
      can make diagnosis of the cause complex. Common early warning signs of
      hypoglycaemia include blurred vision, dizziness, shakiness, sweating,
      irritability, nausea and palpitations, progressing to confusion, syncope,
      headache and disturbances of vision. Loss of consciousness and convulsions may
      follow if corrective steps are not taken to increase blood glucose concentration.
      In rare cases death may occur if blood glucose remains low for 12 hours or more,
      as brain function is reduced and cannot be sustained. However, death from
      hypoglycaemia is avoidable. Causes of non-diabetic hypoglycaemia are an under
      reported area in the nursing and wider literature. This article aims to help
      nursing staff recognise the types and causes of this condition.

PMID- 21894675
TI  - NHS job applications: a guide for nursing students.
AB  - For nursing students approaching the end of their training, securing a job,
      possibly within the NHS, is the next step in their career. This article discusses
      how an NHS job application should be completed. It outlines the most important
      sections in a typical application form and explains what the potential employer
      is looking for, offering advice on how nursing students can demonstrate that they
      have the relevant skills, knowledge or experience. An awareness of current
      professional nursing issues and how these might affect patient care is essential,
      and particular areas of interest will be discussed.

PMID- 21894676
TI  - Domestic violence.

PMID- 21894677
TI  - Wound care for injecting drug users: part 1.
AB  - Part one of this article focuses on the types of injection-related wounds that
      may occur in the intravenous (IV) drug user. Strategies are identified to manage
      the complex needs of this patient group and practical guidance about treatment is
      provided to help promote good patient outcomes. The importance of nutrition in
      promoting wound healing is outlined. Part two next week will discuss specifically
      the assessment and management of leg ulcers in IV drug users.

PMID- 21894678
TI  - Polyhexamethylene biguanide dressings in wound management.
AB  - This article describes wound management using polyhexamethylene biguanide
      dressings in two patients experiencing multiple comorbidities. Wound bed
      debridement and bioburden management were important factors in achieving positive
      results in terms of promoting wound healing and reducing infection and malodour.

PMID- 21894679
TI  - Take part, get results.

PMID- 21894680
TI  - Be one degree above the rest.

PMID- 21894681
TI  - Exchange of ideas.

PMID- 21894682
TI  - The platelet: uses in dentistry.

PMID- 21894683
TI  - Platelet dyscrasias.

PMID- 21894684
TI  - [Characteristics and superiorities of acupuncture medicine].
AB  - Four characteristics and five major superiorities of traditional Chinese
      acupuncture was expounded in this article. The four characteristics are (1)
      theoretical characteristic which focuses on meridians, acupoints, circulation of
      qi and blood; (2) effect mechanism of disease prevention and treatment based on
      external stimulation and internal regulation; (3) clinical diagnosis with the
      combination of differentiation of syndromes according to meridians and
      collaterals, zang-fu organs, eight principles and diagnosis based on acupoints;
      (4) technical characteristic of adoption of unique apparatus and special
      manipulations. The five superiorities are (1) diagnosis: simple, rapid and
      accurate; (2) technique: easy to study and manipulate; (3) therapeutic effect:
      quick and obvious effect, extensive indications; (4) safety: non-toxic and less
      side-effects; (5) cost: comparatively cheap. Thus, it is held that acupuncture
      should play a more important role in medical service system with unique Chinese
      characteristics.

PMID- 21894685
TI  - [Pressing acupoint Danzhong (CV 17) for constipation].

PMID- 21894686
TI  - [Randomized controlled study on rehabilitation of hemiplegia in cerebral
      infarction at the early stage with acupuncture and moxibustion based on meridian
      harmonization and zang-organ regulation].
AB  - OBJECTIVE: To explore the better therapeutic method for the treatment of
      hemiplegia in cerebral infarction. METHODS: One hundred and fifty cases were
      randomized into a meridian-harmonization group (group A), a zang-organ regulation
      group (group B) and a meridian-harmonization and zang-organ regulation group
      (group C), 50 cases in each one. On the basis of conventional treatment, in group
      A, the acupoints were selected along meridians, such as Hegu (LI 4), Taichong (LR
      3), Jianyu (LI 15), Waiguan (TE 5), Huantiao (GB 30) and Yanglingquan (GB 34)ect.
      In group B, the acupoints were selected in light of abdominal acupuncture such as
      Zhongwan (CV 12), Xiawan (CV 10), Qihai (CV 6), Guanyuan (CV 4), Shangqu (KI 17,
      healthy side) and Daheng (SP 15)etc. In group C, the acupoints in group A and
      group B were selected in combination. Before and after treatment, all the
      patients received the test of Barthel Index (BI) to assess the disability level
      and the simple Fugl-Meyer Motor Scale (FMMS) for the evaluation of motor
      function. RESULTS: After treatment, all the three groups presented the
      significant improvement of BI, the down-regulation of disability rate and up
      regulation of FMMS score, indicating significant differences in statistics as
      compared with those before treatment (P < 0.05, P < 0.01). In group C, the
      results of BI improvement, the down-regulation of disability rate and the
      improvement of limb motor function were all superior to those in either group A
      or group B (P < 0.05, P < 0.01). CONCLUSION: Acupuncture in light of meridian
      harmonization and zang-organ regulation is the better approach for the early
      stage rehabilitation of hemiplegia in cerebral infarction and its efficacy is
      superior to that of either simple meridian harmonization therapy or zang-organ
      regulation therapy.

PMID- 21894687
TI  - [Effect on PGF2alpha in plasma in primary dysmenorrhea treated with eye
      acupuncture].
AB  - OBJECTIVE: To observe the clinical curative effect of primary dysmenorrhea and
      the content of prostaglandin F2alpha (PGF2alpha) in peripheral blood of menstrual
      periods treated with eye acupuncture therapy. METHODS: One hundred and ten cases
      of primary dysmenorrhea were randomly divided into an eye acupuncture group (60
      cases) and a medication group (50 cases). In eye acupuncture group, low energizer
      area, liver area, kidney area, heart area and spleen area etc. were selected
      according to the differentiation, and the eye acupuncture therapy was applied. In
      medication group, Ibuprofen Sustained Release Capsules was taken with oral
      administration for 300 mg 1-2 days before menses coming or when the symptoms
      appeared, once every 12 hours, for 3-5 days totally. Three menstrual periods made
      one session. The content of PGF2alpha in peripheral blood, and the curative
      effects and recurrence 3 and 6 months after treatment were observed. RESULTS:
      After 3 months treatment, compared with the curative effects between both groups,
      the cured rate was 55.0% (33/60) and the total effective rate was 95.0% (57/60)
      in eye acupuncture group, which were superior to those of 34.0% (17/50) and 82.0%
      (41/50) in medication group (both P < 0.05). According to the following-up after
      6 menstrual periods, the recurrence rate was 9.1% (3/33), inferior to that of
      35.3% (6/11) in medication group. The contents of PGF2alpha in peripheral blood
      of menstrual periods were all reduced after treatment in two groups (both P <
      0.01). CONCLUSION: The curative effect of primary dysmenorrhea treated with eye
      acupuncture is favorable, and the lever of PGF2alpha in peripheral blood of
      menstrual periods is reduced.

PMID- 21894688
TI  - [Effect of electroacupuncture on oocyte quality and pregnancy for patients with
      PCOS undergoing in vitro fertilization and embryo transfervitro fertilization and
      embryo transfer].
AB  - OBJECTIVE: To observe the impacts of electroacupuncture (EA) on oocyte quality
      and pregnant outcome for the patients with polycystic ovary syndrome (PCOS)
      undergoing in vitro fertilization and embryo transfer (IVF-ET) and explore its
      potential mechanism. METHODS: Sixty-six patients with PCOS and undergoing IVF-ET
      were divided into two groups randomly, including an observation group (34 cases)
      and a control group (32 cases). Ethinylestradiol and cyproterone acetate tablets
      and gonadotropin-releasing hormone agonist were administered for long-program
      superovulation in either group. In observation group, the intervention of EA was
      applied to Guanyuan (CV 4), Zhongji (CV 3), Sanyinjiao (SP 6), Zigong (EX-CA 1)
      and Taixi (KI 3) additionally. The pregnant outcome and the levels of stem cell
      factor (SCF) in the serum and follicular fluid on the day of egg collection were
      compared between two groups. RESULTS: The score of kidney deficiency symptoms
      reduced remarkably after treatment in either group and the improvement in
      observation group was superior to that in control group (P < 0.01). The
      fertilization rate [(76.25 +/- 20.33)% vs (66.34 +/- 15.44)%], cleavage rate
      [(98.66 +/- 3.70)% vs (94.47 +/- 9.45)%] and the rate of high-quality embryos
      [(60.20 +/- 22.20)% vs (50.55 +/- 16.15)%] in observation group were all superior
      to those in control group separately (all P < 0.05). Clinical pregnancy rate
      (46.67%, 14/30) in observation group was higher than that (37.93%, 11/29) in
      control group, but without statistical difference (P > 0.05). SCF levels in the
      serum and follicular fluid on the day of ovary collection were higher obviously
      than those in control group (all P < 0.05). CONCLUSION: Electroacupuncture plays
      an active role in the pregnant outcomes of PCOS patients undergoing IVF-ET and it
      can relieve the symptoms of kidney deficiency in terms of TCM and improve
      clinical pregnant rate. The results are relevant with the overall adjustment of
      organic endocrinal system and the local micro-environment of ovary and the
      improvement of oocyte quality through the up-regulation of SCF level in
      mechanism.

PMID- 21894689
TI  - [Treatment of autism with scalp acupunctur].
AB  - OBJECTIVE: To verify the efficacy on autism treated with scalp acupuncture for
      regaining the consciousness and opening the orifice in children. METHODS: Seventy
      cases of child autism were divided into an observation group (30 cases) and a
      control group (40 cases). In observation group, the cases were treated with scalp
      acupuncture for regaining the consciousness and opening the orifice, in
      combination with music therapy and structure education method. Scalp acupuncture
      was applied to intelligent nine needles (frontal five needles, Sishencong (EX-HN
      1)), affection area, heart and liver area, once a day, at the interval once every
      one week. Totally, 60 treatments made one session. In control group, music
      therapy and structure education method were applied simply. Clancy Autism
      Behavior Scale, Childhood Autism Behavior Scale (CARS), Autism Behavior Checklist
      (ABC) and Gesell Developmental Scale (social adaptive behaviors and language
      development) were adopted to assess the scores before treatment and after 1
      session of treatment. RESULTS: After treatment, the scores in Clancy Autism
      Behavior Scale, CARS and ABC were lower apparently in observation group as
      compared with those before treatment (all P < 0.01), and the scores in Clancy
      Autism Behavior Scale and ABC were lower than those in control group (both P <
      0.01). In observation group, the scores of social adaptive behavior scale and
      language development scale were improved obviously after treatment (both P <
      0.01), which were all higher than those in control group (both P < 0.01). In
      observation, between the group aged from 4 to 6 years and the group aged from 2
      to 3 years, the value differences in Clancy Autism Behavior Scale, ABC and social
      adaptive development scale did not present statistical significance in group
      comparison before and after treatment (all P > 0.05). CONCLUSION: Scalp
      acupuncture for regaining the consciousness and opening the orifice can
      significantly improve the efficacy on autism, effectively relieve child autism
      symptoms and enhance the intelligence, language ability and social adaptive
      ability. Moreover, the efficacy cannot be impacted by child's age.

PMID- 21894691
TI  - [Acupuncture for 62 cases of urinary infection of diabetes].

PMID- 21894690
TI  - [Clinical observation on simple obesity treated by acupuncture].
AB  - OBJECTIVE: To evaluate the effectiveness and safety of simple obesity treated by
      acupuncture. METHODS: By randomized single-blind clinical trial, one hundred and
      eighteen cases of simple obesity were divided into an acupuncture group (76
      cases) and a placebo-acupuncture control group (42 cases), additionally, health
      control group (30 cases) was included. In acupuncture group and placebo
      acupuncture control group, all the patients received a restricted diet; Zhongwan
      (CV 12) and Zhongji (CV 3) etc. at abdomen and Liangqiu (ST 34) and Zusanli (ST
      36) etc. at limbs were selected; body mass index (BMI), Serum Total Cholesterol,
      triglyceride (TG), Glucose, Creatinine, urea nitrogen (BUN), Uric Acid and
      adverse reactions scores were observed. RESULTS: After treatment the BMI in
      acupuncture grown was lower than that in placebo-acupuncture control group (P <
      0.01). In metabolism indices, the serum Total Cholesterol and Glucose after
      treatment were reduced obviously than those before treatment in acupuncture group
      (all P < 0.01), and there was no significant differences in other metabolism
      indices (all P > 0.05) in two groups. After treatment, in adverse reactions
      scores, the hunger sensation scores in acupuncture group was reduced than that in
      placebo-acupuncture control group (P < 0.05), and there was no significant
      differences in other indices (all P > 0.05). CONCLUSION: BMI of simple obesity
      was reduced by acupuncture, and the Serum Total Cholesterol and Glucose were
      reduced accordingly. The adverse reac tions such as weakness, nervosa and
      diarrhea, etc. doesn't appear after acupuncture treatment. Acupuncture therapy is
      one of the safe and effective methods for simple obesity.

PMID- 21894692
TI  - [Plum-blossom needle, cupping combined with electroacupuncture for traumatic
      myositis ossificans of elbow joint in early stage].

PMID- 21894693
TI  - [Discussion on the meridian therapy of headache].

PMID- 21894694
TI  - [Study on signal transmission characteristics of meridian based on electrical
      network theory and experiments].
AB  - Study on features of acupoints with resistance test in the past half century is
      reviewed in this article. Mechanism and technology of the method are introduced
      as well as its shortcomings. The determination method of signal transmission
      along meridians with the combination of electrical network theories and practice
      is advanced. And the result of a series experiments on one meridian at the
      superficial part of the body are given as well. Thus, it is concluded that the
      signals of the point-in/point-out and the signals along a non-meridian path with
      the same distance are significantly different, which gives a verification of the
      feasibility of the method by using electrical network theories to set out
      characteristics of signal transmission along meridians dynamically.

PMID- 21894695
TI  - [Study on origin of meridians and collaterals through pain relieving effect of
      muscle regions].
AB  - Through analysis on sequencing of meridians and their muscle regions, their
      pertaining organs, run ning courses, linking and indications described in Zubi
      Shiyimai (Eleven Meridian of Foot and Hand), Yinyang Shiyimai (Eleven Meridian of
      Yinyang), Lingshu: Jingmai (Miraculous Pivot: Meridian) and Lingshu: Jinjing
      (Miraculous Pivot: Muscle Meridian), it is found that most of the indications of
      acupuncture in ancient time are symptoms of the muscle regions. 62.59% points of
      the national standard acupoints location close to tender points of the muscle
      regions, which indicates that the origin of early acupoints are tender points
      along the running courses of the muscle regions. Thus, it is concluded that
      meridians and their muscle regions have the same origin, which provides new train
      of thinking for a better comprehension of origin of meridians and collaterals.

PMID- 21894696
TI  - [Fifty-two cases of female stress urinary incontinence treated by acupuncture and
      moxibustion].

PMID- 21894697
TI  - [Experimental study on electric impedance of acupuncture based on the midnight
      noon ebb-flow theory].
AB  - OBJECTIVE: Relationship among three point selection methods based on the midnight
      noon ebb-flow theory, namely Najia fa (day- prescription of acupoints), Nazi fa
      (hour-prescription of acupoints) and Yangzi Shike Zhuxue fa (point-open method
      based on the mother and son relation as well as the hours and its divisions),
      were approved in the article, which provided the scientific validity of the
      correlation among three point selection methods of midnight-noon ebb-flow theory.
      METHODS: Electric impedance on relevant acupoints of 30 health subjects on the
      period of the day of Zishi (from 11:00 p.m. to 1:00 a.m.), Maoshi (from 5:00 a.m.
      to 7:00 a.m.), Wushi (from 11:00 a.m. to 1:00 p.m.) and Youshi (from 5:00 p.m. to
      7:00 p.m.) were tested with NQ-1B conductivity meter. And statistical analysis
      was made on the testing results. RESULTS: The daily average value of the method
      of Najia fa in 1 circle of the midnight-noon ebb-flow theory was 0.459omega, the
      value of the method of Nazi fa was 0.553omega, and the Yangzi Shike Zhuxue fa was
      0.533omega. At the same time, it presented a tendency of first raising and then
      declining from Zishi to Youshi with the peak appears at Maoshi and the valley at
      Youshi. The differences of comparison of the average electric impedance between
      Najia fa and Nazi fa, Najia fa and Yangzi Shike Zhuxue fa were considered
      statistical significant (both P < 0.001). When 2 values of different methods
      within the same hours were compared, the value difference between Najia fa and
      Nazi fa in the time period of Wushi and the difference between Najia fa and
      Yangzi Shike Zhuxue fa in the time period of Wushi were considered statistical
      significant (P < 0.001, P < 0.01). CONCLUSION: The changing tendency of electric
      impedance of different point selection methods based on midnight-noon ebb-flow
      theory is similar, however, with weak relevance. Moreover, obvious differences
      can still be found in point location and time selection.

PMID- 21894698
TI  - [Thirty-one cases of cerebral infarction treated with acupuncture and oxygen
      driven atomizing inhalation].

PMID- 21894699
TI  - [Single point and two-step acupuncture treatments for shoulder periarthritis].

PMID- 21894700
TI  - [Experimental study on anti-inflammatory and analgesic effects of
      electroacupuncture combined with medium frequency therapy in model rats with
      lumbar nerve root compression].
AB  - OBJECTIVE: To explore the effects and mechanism of electroacupuncture combined
      with medium frequency therapy on lumbar nerve root compression. METHODS: Seventy
      two Sprague-Dawley (SD) rats were randomly divided into a normal group, a sham
      operation group, a model group, an electroacupuncture group (EA group), a medium
      frequency group(MF group) and an electroacupuncture combined with medium
      frequency group (EA + MF group), twelve rats in each group. Models were
      established by surgery except the normal group and the sham operation group. Rats
      in the normal group, the sham operation group and the model group were not
      treated. In the EA group, the rats were treated by electroacupuncture at "Jiaji"
      (EX-B 2) and "Huantiao" (GB 30) etc., and by medium frequency at the "Jiaji" (EX
      B 2) and "Huantiao"(GB 30) in the MF group. Rats in the EA + MF group were
      treated by both electroacupuncture and medium frequency. All treatments were
      started on the fifth day of established model, once a day for fourteen days.
      Rats' lower limb functions were observed before and after treatment, thromboxane
      B 2 (TXB 2) and prostacyclin F1alpha (PGF1alpha) in blood plasma were tested
      after treatment, and pathological changes in the local compressed nerve root were
      observed by light microscope. RESULTS: After treatment, the scores of rats' lower
      limb neurologic function in three therapy groups were significantly lower than
      before (all P < 0.01). Compared with the model group, TXB 2 in the EA group and
      the EA + MF group after treatment were decreased significantly (both P < 0.01),
      and PGF1alpha in the EA + MF group was increased significantly (P < 0.01), and
      TXB 2/PGF1alpha level were all regulated favorably in three therapy groups (all P
      < 0.01), and the pathological scores in the EA group and the EA + MF group were
      improved significantly (both P < 0.01). CONCLUSION: n Electroacupuncture combined
      with medium frequency has anti-inflammatory and analgesic effects in model rats
      with lumbar nerve root compression, and its mechanism may be related with the
      regulation of homeostasis M between TXB 2 and PGF1alpha so as to improve
      microcirculation.

PMID- 21894701
TI  - [Effects of eye-acupuncture therapy on the expression of AQP4 in brain tissue of
      rats with acute cerebral ischemia-reperfusion injury].
AB  - OBJECTIVE: To explore the mechanism of the eye-acupuncture for treatment of acute
      cerebral ischemia-reperfusion injury. METHODS: Thirty-two healthy SD rats were
      randomly divided into a normal group, a sham operation group, a model group and
      an eye-acupuncture group, 8 rats in each group. The rat model of cerebral
      ischemia-reperfusion was established with thread occlusion method in the model
      group and the eye-acupuncture group. The eye-acupuncture group was treated by eye
      acupuncture at "liver region", "upper energizer area", "lower energizer area" and
      "kidney region" for 20 min immediately after reperfusion and at 30 min before
      sampling. No treatment was done in the normal group and the sham operation group,
      and no thread occlusion was performed in the sham operation group. The Neurologic
      impairment was scored and the methods of immunohistochemistry staining, western
      blotting and real-time fluorescent quantitation polymerase chain reaction (RQ
      PCR) were taken to detect the expression of the aquaporin protein 4 (AQP4) and
      its mRNA in cerebral cortex after reperfusion for 3 hours. RESULTS: The
      neurologic impairment score of 1.50 +/- 0.54 in the eye-acupuncture group was
      significant lower than 2.63 +/- 0.92 in the model group (P < 0.01). The
      expression of the AQP4 protein by immunohistochemistry and western-blot
      respectively were 116.33 +/- 10.24 and 0.53 +/- 0.04 in the normal group, 118.97
      +/- 12.72 and 0.55 +/- 0.07 in the sham operation group, and 129.30 +/- 18.36 and
      0.67 +/- 0.08 in the eye-acupuncture group, with statistical significance
      compared to 150.88 +/- 15.82 and 0.94 +/- 0.04 in the model group (all P < 0.01),
      and there were significant differences between the eye-acupuncture group and the
      normal group (both P < 0.01). The tendency in the expression of AQP4 protein and
      its mRNA in all the group were almost the same. CONCLUSION: The eye-acupuncture
      therapy can relieve the cerebral ischemia-reperfusion injury and the protective
      mechanism is related to the downregulation of the cerebral AQP4 expression.

PMID- 21894702
TI  - [Ling's acupoint selection and needle-inserting techniques].

PMID- 21894704
TI  - [Scraping and blood-letting therapy for chronic eczema].

PMID- 21894703
TI  - [Indications of acupuncture outpatient based on clinical investigation].
AB  - OBJECTIVE: The present situation of clinical indications of acupuncture in China
      is investigated in this article which provides clinical evidence for the
      establishment of acupuncture indications. METHODS: Out-patients of acupuncture
      departments of 31 Chinese provinces in the year 2008 were investigated through
      the method of cluster random sampling. And the analysis was made on diseases
      sorting and distribution based on Pareto principle and with EpiMap software.
      RESULTS: Information of 31 858 out-patients of the first treatment from 36
      hospitals were collected which referred to 368 diseases of 16 disease systems.
      Among them, there were 57 most commonly-encountered diseases, 60 commonly
      encountered diseases and 251 rare diseases. CONCLUSION: There are totally 368
      acupuncture clinical indications at present according to the investigation with
      disproportional distribution in administrative districts. It is held that
      indications of acupuncture have high centralization degree. Thus, the populariza
      tion and promotion on application of acupuncture indications should be
      strengthened.

PMID- 21894706
TI  - [Comparative observation of efficacy on lumbar disc herniation treated with
      acupotomology and operation].
AB  - OBJECTIVE: To compare the efficacy difference between acupotomology and operation
      in the treatment of lumbar disc herniation (LDH). METHODS: One hundred and eighty
      four cases were randomized into an acupotomology group (109 cases) and an
      operation group (75 cases). In acupotomology group, acupotomology was applied to
      relevant local soft tissues in LDH and the reactive points in the distribution of
      superior gluteal nerves, at the outlet of sciatic nerve and in the nerve
      innervate area of the lower extremities separately. In operation group, the small
      windowed discectomy through small incision was adopted. The clinical efficacies
      were assessed between two groups. RESULTS: In acupotomology group, the clinical
      cured rate was 82.6% (90/109) and the effective rate was 96.3% (105/109). In
      operation group, they were 86.7% (65/75) and 97.3% (73/75) respectively. There
      were no significant differences in statistics between two groups (both P > 0.05).
      CONCLUSION: Acupotomology is definitely effective in the treatment of lumbar disc
      herniation and its efficacy is similar to that of operation.

PMID- 21894705
TI  - [Analgesic effect of acupuncture at Neimadian(Extra) in postoperation of
      abdominal surgery].
AB  - OBJECTIVE: To observe the analgesia effectiveness and safety of
      electroacupuncture at Neimadian(Extra) for postoperation of abdominal surgery.
      METHODS: One hundred and twenty patients with routine abdominal surgery were
      randomly divided into an acupuncture group and a medication group, 60 cases in
      each group. The acupuncture group was treated with electroacupuncture at
      Neimadian(Extra), which was located on the inside of lower leg, 7 cun above the
      internal malleolus and 0.5 cun from post edge of tibial. The medication group was
      treated with patient-controlled intravenous analgesia (PCIA) with Sufentanil.
      After the treatment, the Visual Analogue Scale (VAS), the security, the analgesic
      effect and beta-endorphin content were compared. RESULTS: The postoperative VAS
      score at 2, 4, 8, 16, 24 and 48 h in the acupuncture group was lower than those
      in the medication group (all P < 0.05). The analgesic effect at 2, 4, 16 and 24 h
      after surgery in the acupuncture group were superior to those in the medication
      group (P < 0.05, P < 0.01). The beta-endorphin content at 0, 8, 16 and 48 h after
      surgery in both groups were increased, and the acupuncture group was superior to
      the medication group (all P < 0.05). The security class after surgery in the
      acupuncture group was higher than that in the medication group (P < 0.05).
      CONCLUSION: The analgesic effect and safety of electroacupuncture at
      Neimadian(Extra) in postoperation of abdominal surgery are superior to those of
      the PCIA with Sufentanil.

PMID- 21894707
TI  - [Analysis case of electrolysis phenomenon caused by electroacupuncture accident].

PMID- 21894708
TI  - [Suggestions of making filiform needles with color needle handle].

PMID- 21894709
TI  - [Globalization of acupuncture technology innovation: a quantitative analysis
      based on acupuncture patents in the U.S.A].
AB  - The structure of international flow of acupuncture knowledge was explored in this
      article so as to promote the globalization of acupuncture technology innovation.
      Statistical methods were adopted to reveal geographical distribution of
      acupuncture patents in the U.S.A. and the influencing factors of cumulative
      advantage of acupuncture techniques as well as innovation value of application of
      acupuncture patents. Social network analysis was also utilized to establish a
      global innovation network of acupuncture technology. The result shows that the
      cumulative strength on acupuncture technology correlates with the patent
      retention period. The innovative value of acupuncture invention correlates with
      the frequency of patent citation. And the U. S. A. and Canada seize central
      positions in the global acupuncture information and technology delivery system.

PMID- 21894710
TI  - [Forty-eight cases of abducent paralysis treated with electroacupuncture at
      Jianming 3(Extra) and Shangming(Extra)].

PMID- 21894711
TI  - [Guiding principles of design in acupuncture RCTs].
AB  - For the problems specifically associated with conducting randomized controlled
      trials (RCTs) research into acupuncture, studies focus on these factors of sample
      population, test quality, baseline, diagnostic criteria, inclusive and exclusive
      criteria, the choice of control group, the interventions, efficacy evaluation,
      standardization and objective observation indice, long-term follow-up, and
      adverse reaction. Sound suggestions are provided to improve the quality of
      acupuncture research.

PMID- 21894712
TI  - [Gastrointestinal neurosis treated by blood-letting].

PMID- 21894713
TI  - [Case of Huntington's disease].

PMID- 21894715
TI  - [Senile frequent micturition treated with moxibustion on Yongquan(KI 1)].

PMID- 21894714
TI  - [Discrimination on diseases originated from Foot-Taiyin meridian].
AB  - Through the analysis on the form, origin and evolution of diseases originated
      from Foot-Taiyin Meridian, and the investigation on clinical practice, it is held
      that diseases originated from Foot-Taiyin meridian were developed on the base of
      supplement and adaption of the ancient medical classics. And it is also held that
      great respect on clinical practice was attached by the compiler.

PMID- 21894716
TI  - [Analysis on the situation of adverse reaction to acupuncture and acupuncture
      risk].
AB  - The Medline database system and the CNKI literature database were used to
      evaluate the publications in acupuncture in recent years, using the key words:
      "acupuncture" "adverse reaction" and "risk". A number of 155 publications in
      Chinese were collected, including 698 cases; a number of 59 abstracts
      publications in English were selected, including 64 cases. The analysis of the
      publications shows that various causes lead to adverse reactions to acupuncture.
      The defective security system of acupuncture is one of the major causes. It
      demands to promote the safety guidelines issued by WHO or to establish a new
      Chinese security system of acupuncture.

PMID- 21894717
TI  - [Case of ophthalmalgia caused by facial paralysis].

PMID- 21894718
TI  - [Gastrointestinal bleeding in immunocompromised patient].

PMID- 21894719
TI  - Repair of a common bile duct injury.

PMID- 21894720
TI  - [Teaching in gastroenterology].

PMID- 21894721
TI  - [Emil Theodor Kocher].

PMID- 21894722
TI  - [Study of prognostic factors in the hepatectomy for metastases of colorectal
      carcinoma--analysis of two scores].
AB  - BACKGROUND: Resection is the treatment of choice for colorectal cancer liver
      metastases. OBJECTIVE: This is a retrospective, longitudinal, retrospective
      analysis of different prognostic factors for survival in a consecutive series of
      liver resection for metastatic colorectal carcinoma. PATIENTS AND METHODS:
      Between October 1998 and November 2007, we performed 89 liver resections for
      colorectal metastases. A retrospective analysis from the liver resection database
      was performed and the variables analyzed were related to demography, primary
      tumor and surgical procedure. Survival analysis was performed according to the
      Fong and Basingstoke scores. RESULTS: The mean age of patients was 60.5 years and
      67.4% were men. The primary tumor was localized in the colon in 73% of cases. In
      68.5% the metastases were metachronous. The right hemiliver was involved in 46
      patients (52%). Major hepatectomy was performed in 36 (40.2%), minor in 55
      (59.8%) and combined procedures in 14 (15.7%). Seventy-seven (86.5%) R0
      resections were achieved. Morbidity was 32.6%, with no perioperative mortality.
      Average follow-up was 32.5 months (range 1 to 158 months), with a median of 25.5
      months. Median overall survival was 69.7 months and mean disease-free survival
      58.7 months. Multivariate analysis found statistical significance for blood
      product requirement and margin of resection. Thirty-four patients are alive at
      the end of this study (45.9%). The Basingstoke predictive index for postoperative
      variables showed significant differences that were not demonstrated by the Fong
      clinical score on prognostic factors. CONCLUSIONS: The application of Basingstoke
      predictive index and Fong score with biomarkers may indicate the most appropriate
      therapeutic strategy in each patient with colorectal liver metastases.

PMID- 21894723
TI  - A meta-analysis of patients with chronic hepatitis C treated with interferon
      alpha to determine the risk of autoimmune thyroiditis.
AB  - OBJECTIVE: In order to analyze the effect on autoimmune thyroiditis (AT) of
      current anti-hepatitis C virus (HCV) treatment in HCV-infected patients, we
      performed a systematic review with meta-analysis of the available literature. The
      present meta-analysis was conducted to evaluate the strength and the consistency
      of the association between treatments with interferon-alpha (IFN-alpha) for HCV
      infection and AT. MATERIAL AND METHODS: A search in Medline, PubMed, and EMBASE
      was conducted with a systematic review of clinical studies in English and other
      languages. Only studies in HCV subjects compared to a control group with
      hepatitis B (positive HBsAg) were considered. The relative risk (RR) of AT was
      regarded as the most reliable outcome end-point. The pooled odds ratio (OR) and
      95% confidence intervals (95% CI) were calculated from the raw study data using
      the Mantel-Haenszel methods. We used a statistical evaluation of heterogeneity by
      the chi2-test to assess whether the variation in treatment effect within trials
      of the same group was greater than it might be expected. RESULTS: We identified
      35 clinical trials with a total of 6.403 patients. Five trials were selected for
      analysis involving a total of 625 patients with hepatitis C treatment with IFN
      alpha and 456 HBsAg-positive controls. These studies yielded a combined adjusted
      OR of 4.98 (95% IC 1.56-15.91). The test for heterogeneity was significant (P =
      0.0008), and the test for overall effect was Z statistic 2.71 (P = 0.007).
      CONCLUSION: Our meta-analysis indicates that treatment with IFN-alpha for HCV
      infection has an increased risk of AT.

PMID- 21894724
TI  - [Gastric acid suppression of a new oral powder omeprazole suspension for infants
      with gastroesophageal reflux disease. A pilot study].
AB  - BACKGROUND: Gastroesophageal reflux disease (GERD) has a prevalence of 10% to 20%
      in the pediatric population. The 24-hour pHmetry is still considered the "gold
      standard" for its correct diagnosis. Omeprazole is the elective drug for a proper
      treatment. However, there are no adequate pharmaceutical presentation forms for
      infants. OBJECTIVE: To assess the acid suppression capacity of a new
      pharmaceutical association of omeprazole with sodium bicarbonate and sodium
      alginate (OBA), powder for oral suspension, in small infants with GERD. The
      response was measured according to the gastric variations of pH after a 3-day
      treatment with OBA. PATIENTS AND METHOD: This is a pilot, prospective, open study
      in infants with no congenital nor associated anomalies under 12 months of age
      with GERD. Two double channel pHmetry with gastric sensor were performed on
      different days in the same patient. The first one to establish the diagnosis (day
      0) and the second one (day 3) after receiving omeprazole (OBA) at 1.5 mg/kg/day
      in a twice/dose/day (BID). RESULTS: The comparison between the frst and the
      second gastric pHmetry showed a statistically significant reduction in gastric
      acidity. No adverse events were observed in infants and the suspension flavor was
      palatable. CONCLUSIONS: This new presentation of omeprazole (OBA) with sodium
      bicarbonate and sodium alginate powder for oral suspension is capable of a
      significant and intense acid suppression, necessary for treatment of infants with
      GERD. The taste of the solution was well accepted by all the babies, which is a
      very important finding for this age group.

PMID- 21894726
TI  - [Impact of ishemia-reperfusion injury on long survival rate in intestinal
      transplantation in rats].
AB  - INTRODUCTION: The intestine is a highly sensitive tissue to ischemia-reperfusion
      (IR) injury that will early respond increasing its permeability. Later this
      response is translated in morphologic and histological changes that reveal the
      degree of damage. The heterotopic intestinal transplantation model in rats allows
      to evaluate the evolution of intestinal tissue injury after ischemia-reperfusion
      without affecting the long survival rate. OBJECTIVE: The aim of this paper is to
      establish a relationship between the ischemic reperfusion injury with the long
      term survival METHODS: Ten intestinal transplants were analyzed in adult, Wistar,
      inbred, male rats. Light microscopical examination was performed on intestine
      graft: 1) immediately post-dissection, 2) at the end of cold isquemia, 3) 30 min,
      4) 48hs and 5) 5 days post-transplant procedure, respectively. Biopsies were
      reported according to Park's classification and extension of staining using
      immunohistochemestry to malondialdehyde (MDA) products. RESULTS: The Park's
      classification indexes reported in samples were 1) 0,57 +/- 1,13 (N=10); 2) 2,71
      +/- 1,25 (N=10); 3) 4,14 +/- 0,89 (N=10); 4) 1,0 +/- 0,81 (N=7); 5) 0 (N=7). The
      highest levels of immunohistochemical detection of MDA were observed thirty
      minutes post-reperfusion (extension of staining between 51% to 75%). Three
      animals died when they were sampled at 48 hours, and the biopsies had Park's
      classification > or = 4 at 30 minutes post-reperfusion and endotoxemic signology.
      CONCLUSIONS: The highest degree of mucosal damage was observed immediately post
      reperfusion. At 48hs the graft tended to be normalized Failure to repair the
      immediately I-R injury signficantly affects the long term survival.

PMID- 21894725
TI  - [Superselective embolization in the treatment of massive gastrointestinal
      bleeding].
AB  - INTRODUCTION: Massive lower gastrointestinal (LGI) bleeding is a severe clinical
      picture associated with high mortality in hospitalized patients with
      comorbidities. Current international publications have highlighted the role of
      embolization in the treatment of this pathology, although there is little
      experience in Latin America. The aim of this paper is to describe a series of
      cases treated in the same institution using embolization as safe and effective
      treatment of massive LGI bleeding. PATIENTS AND METHODS: The embolization was
      performed by superselective catheterization after a percutaneous transfemoral
      approach. RESULTS: We included 26 patients (10 women) with mean age of 62 years
      old (range 2 to 92 years). Twenty-five (96%) patients had comorbidities,
      including bleeding disorders in 18 cases (69%). All patients had hematochezia,
      hypotension and/or hypovolemic shock, requiring transfusion of red blood cells
      (mean 3.8 units, range 2 to 12 units). The embolization was effective in stopping
      bleeding in 24 patients (immediate success rate of 92%). There was no digestive
      tract infarction or complications related to the procedure. CONCLUSIONS:
      Superselective embolization of the massive LGI bleeding was safe and effective in
      this series of patients. Embolization is recommended as the treatment of choice
      to stop massive LGI bleeding in centers that have the appropriate human and
      technological resources.

PMID- 21894727
TI  - [Hereditary nonpolyposis colorectal cancer: analysis of a case and review of
      management].
AB  - INTRODUCTION: Hereditary nonpolyposis colorectal cancer (HNPCC), also known as
      Lynch syndrome, represents 5% to 7% of colorectal cancers. It is an autosomal
      dominant inherited disorder characterized by an early onset of colorectal tumors,
      predominantly proximal, and multiple and microsatellite instability. We used the
      Amsterdam II criteria for its identification. OBJECTIVE: To analyze the case of a
      patient with a family history of malignant colorectal tumors at an early age of
      onset. CASE REPORT: A 40-year-old woman, from Valle de Punilla, Cordoba,
      Argentina, with no previous medical history, complained of mild changes in her
      bowel habits and was admitted to the general surgery department with the
      radiographic diagnosis of a tumor in the hepatic flexure of the colon. She
      underwent a right hemicolectomy for a Dukes B stenosing tumor (T3N0M0, stage
      IIa). CONCLUSION: In this report, we present the case of a woman with HNPCC who
      met the Amsterdam II criteria II. Family members who meet these criteria should
      be screened for the mutation in MMR genes. As genetic tests are not routinely
      available, an annual colonoscopic surveillance of all asymptomatic relatives
      older than 25 to 30 years old who meet the criteria is recommended, regardless of
      the availability and/or the outcome of genetic testing.

PMID- 21894728
TI  - [Diffuse gastric cancer associated with Menetrier's disease].
AB  - BACKGROUND: Menetrier's disease is a rare disease of the stomach generally
      described as hypertrophic gastropathy. Its etiology is unknown and its malignant
      potential is controversial. Only a few reports supporting its association with
      gastric cancer have been found. We present a case of gastric cancer associated
      with Menetrier's disease. CASE REPORT: We present a 72 year-old-male with
      epigastric pain and early satiety during the last 5 months. He had been treated
      with proton pump inhibitors with unfavorable response and began with loss of
      weight and asthenia. An upper digestive endoscopy showed an erythematous nodular
      gastric mucosa, with enlarged folds. An abdominal CT scan demonstrated a
      circumferential parietal thickening of the gastric wall and adenopathies. A
      gastric macrobiopsy done by endoscopic mucosal resection evidenced a mucin
      infiltrating adenocarcinoma with invasion of the lamina propria. Subtotal
      gastrectomy was done. The histology showed a stomach with changes compatible with
      Menetrier's disease and diffuse infiltration by a highly undifferentiated
      adenocarcinoma (plastic linitis). CONCLUSION: A patient with diffuse gastric
      adenocarcinoma and Menetrier's disease is reported.

PMID- 21894730
TI  - AWHONN and the Women and Children's Health Chapter of SCNA present joint workshop
      -"Clinical Refresher in Maternal Child Topics 2011".

PMID- 21894732
TI  - Kids need restraints.

PMID- 21894731
TI  - Seeking the spark.

PMID- 21894733
TI  - A life in pictures. Taking photos is the best medicine for pediatric surgeon
      Roberta Sonnino.

PMID- 21894734
TI  - Visual cues. A Minneapolis Institute of Arts program aids people with memory
      loss.

PMID- 21894735
TI  - A new leaf. Patients express themselves through clay.

PMID- 21894736
TI  - Study break. Medical students use Art of Medicine awards to explore their
      creative side.

PMID- 21894737
TI  - Uniform design. Scrubs become high fashion.

PMID- 21894738
TI  - An all or nothing career?

PMID- 21894739
TI  - State launches Time Out campaign.

PMID- 21894740
TI  - Medical imaging. Winners of our photo contest.

PMID- 21894741
TI  - Medical musings. Results of our eighth annual writing contest.

PMID- 21894742
TI  - 7 reasons why doctors write.

PMID- 21894743
TI  - Why we need the arts in medicine.

PMID- 21894744
TI  - Tularemia in two South Dakota children.
AB  - Tularemia may be relatively rare in the United States, but physicians must be
      able to recognize it in order to treat it in its earliest stages. They also need
      to understand that most antibiotics are not effective against the disease. This
      article presents two cases oftularemia infection among school-aged children in
      South Dakota who were successfully treated with IV gentamicin and oral antibiotic
      combinations.

PMID- 21894745
TI  - [Nine-year experience in the treatment of patients with diffuse large B-cell
      lymphosarcoma].
AB  - AIM: To ascertain indications to standard (CHOP-21/R-CHOP-21) and intensive (mNHL
      BFM-90) treatment in patients with diffuse large B-cell lymphosarcoma (DLBCL)
      with involvement of lymphoid organs. MATERIAL AND METHODS: The trial, performed
      from January 2002 to December 2010, enrolled 139 DLBCL patients with affected
      lymph nodes (LN), tonsils, spleen, bone marrow (BM). The diagnosis was made
      according to WHO criteria. The patients were examined according to the protocol
      of lymphoproliferative diseases. Biopsy material from all 139 patients was
      studied immunohistochemically on paraffin blocks (LN, tonsils, spleen, BM) using
      a wide panel of antibodies. The same examinations of BM were made in all 18 cases
      of BM involvement. Cytogenetic examination was performed in 106 patients: 48
      standard cytogenetic tests, 139 - FISH for t (14;18) as well as rearrangement of
      locus 3q27. Patients with a poor prognosis (n = 86, 61.8%) received intensive
      therapy according to mNHL-BFM-90 program. The signs of a poor prognosis were the
      following: massive tumor (tumor size more than 7.5 cm), invasion into the
      adjacent organs or tissues, stage III-IV disease by Enn-Erbor, high concentration
      of LDG. Patients without a poor prognosis (n = 53, 38.2%) received standard
      treatment CHOP-21 (n = 28) or R-CHOP-21 (n = 25). RESULTS: A complete remission
      without recurrences was achieved in all 53 patients without signs of unfavourable
      prognosis (100%). Overall 5-year survival was 96%, 2 patients died in remission
      of other causes. Of 86 patients with a poor prognosis a complete remission was
      achieved in 64 (74.4%) patients. Overall and recurrence-free 5-year survival was
      65 and 86%, respectively. CONCLUSION: Standard treatment provided long-term
      complete remission in all the patients without poor prognosis. Intensive (mNHL
      BFM-90) treatment produced the best results in generalized lesion without BM
      involvement. Overall 5-year survival was 84% in these patients and 12% in
      patients with BM involvement.

PMID- 21894746
TI  - [First results of Ph-negative acute lymphoblastic leukemia therapy of adults
      according to the protocol of Research Group of Russian Hematological Centers ALL
      2009].
AB  - AIM: To review results of 2-year experience in execution of the protocol on the
      treatment of adult acute Ph-negative lymphoblastic leukemia ALL-2009. MATERIAL
      AND METHODS: Of 111 patients registered in the study from November 2008 to
      December 2010 the analysis covered 96 patients from 23 hematological centers in
      18 towns of the RF. RESULTS: Treatment according to the Protocol ALL-2009
      resulted in achievement of a complete remission in 91.2% patients with low early
      lethality of 5.5%. Postremission lethality fell to 3.7% versus previous studies
      (22%). Overall 2-year survival and recurrence-free survival reached 77.6 and
      78.4%, respectively. Detection of any chromosomic aberrations significantly
      affected recurrence-free survival: 74 vs 100% in patients with normal karyotype.
      CONCLUSION: Protocol All-2009 demonstrates high efficacy in moderate toxicity and
      good reproducibility in any hematologic center.

PMID- 21894747
TI  - [Long-term results of HBV and HCV infection in patients with blood system
      diseases].
AB  - AIM: To specify trends in clinical and laboratory manifestations of virus
      hepatitis B and C (HBV and HCV) in patients with blood diseases from the moment
      of the first positive specific tests for HBV and HCV markers; to assess effects
      of HBV and HCV infection on efficacy of treatment of blood disease treatment,
      i.e. lifespan of patients with hematological diseases. MATERIAL AND METHODS: The
      study enrolled 257 patients: 205 with acute leukemia - AL, 40 with
      lymphoproliferative diseases, 4 - with CML and 8 - others; 8 healthy bone marrow
      donors. The patients were admitted to Russian Hematological Research Center in
      2004-2006 Follow-up median was 253 days. A total of 7800 biological samples were
      studied, among them about 4000 tests for HBV DNA and HCV RNA. RESULTS: Positive
      tests for specific markers of HBV and HCV were absent only in 78 (29.4%)
      patients. Positive markers of coinfection were detected in 57 (32.8%) of 174
      patients with HBV infection and in 81.4% of 70 patients with HCV infection.
      Probability of detection of HCV markers after positive tests for HBV markers and
      vice versa is about 3 times higher than probability of their isolated detection.
      Among patients infected with HBVsymptoms of hepatitis B are likely to appear in
      56% patients to day 500 of follow-up from the date of the first positive specific
      test. Median of the interval between the first positive test for HBV markers and
      probable clinical signs of hepatitis was 30 days. Among patients with HCV
      infection, 85% develop hepatitis to follow-up day 300 since the date of the first
      specific positive test. Almost 100% patients infected with two viruses develop
      hepatitis to follow-up day 600. Median of the interval between the first positive
      test for HBV and HCV markers and probable hepatitis picture was 47 days. Overall
      3-year survival of AL patients was 40%, of patients with lymphoproliferative
      diseases - 58%. Overall 7-month survival was 75% in AA patients. HBV infection in
      patients with blood disease is associated with high risk of death, especially in
      AA and AL. Association between HCV infection and survival is not proved.
      CONCLUSION: A high rate of clinical realization of viral hepatitis B and C,
      especially in coinfection, calls for virological and clinical monitoring of
      patients with any positive test for HBV and HCV markers.

PMID- 21894748
TI  - [Development of aseptic osteonecrosis during the treatment of acute lymphoblastic
      leukemia: review of the literature and author's own data].
AB  - We report a case of aceptic osteonecrosis (AON) of the left hymerus epiphysis in
      programmed treatment of a male patient with lymphoblastic lymphoma to illustrate
      clinical, laboratory, epidemiological, pathogenetic, diagnostic and therapeutic
      aspects of AON in programmed therapy of acute lymphoblastic leukemia (ALL). We
      believe that AON is a rather frequent but often missed for early diagnosis
      complication of ALL treatment. Even a weak pain in bones and joints under
      mechanical load in patients on long-term treatment with glucocorticosteroids is
      an alarming symptom which may indicate a risk of an osteodestructive process and
      relevant diagnostic and therapeutic measures may be needed.

PMID- 21894749
TI  - [Dynamic study of Bcl-2, Bax, p53, and ACE expression in CD34+ cells of
      peripheral blood and bone marrow in acute leukemia patients in the course of
      induction chemotherapy].
AB  - AIM: To determine unbalance in the system of programmed cell death in the cells
      CD34+ of the bone marrow (BM) and peripheral blood (PB) before and after
      cytostatic impact in acute leukemia (AL). MATERIAL AND METHODS: Flow
      cytoflowmetry estimated expression of Bcl-2, Bax, p53 and ACE in the cells CD34+
      of BM and PB from 10 AL (4 AML and 6 ALL) patients. PB and BM samples were
      studied before polychemotherapy (PCT) and in the course of induction treatment:
      on day +8, +21 (blood only), +36 - 38. Control group consisted of 4 BM donors.
      RESULTS: The number of CD34+ cells expressing Bcl-2 in AL patients was 46,5 +/-
      9,35 % in BM and 39,4 + 10,8 % in PB, in healthy donors - 9 and 32,8 %,
      respectively. Bax expression in AL patients' cells CD34+ of BM versus this
      expression in donors was 3 times higher (36,7 +/- 8,1 and 14,8%, respectively),
      of PC - 2 times lower (40,7 +/- 6,59 and 75,8%, respectively). Expression of p53
      in AL patients was 36,8 +/- 9 % in BM and 26 +/- 7,4 % in PB, in donors - 28,2
      and 65 %, respectively. ACE expression on the cells CD34+ in AL patients in early
      disease was 62 +/- 7,57 % in BM and 48 +/- 8,1 % in PB, in donors - 40 and 85 %,
      respectively. Moreover, there were significant changes in expression of Bcl-2 in
      BM and Bax, ACE and p53 in PB in the cells CD34+ in AL patients during and after
      induction PCT. CONCLUSION: The above changes evidence for unbalance of pro- and
      antiapoptosis proteins of regulators in AL patients. PCT changes profile of
      expression of these proteins, but not to the level of healthy donors.

PMID- 21894750
TI  - [Primary mediastinal (thymic) large B-cell lymphoma: review of the literature and
      author's own data].
AB  - AIM: To study morphoimmunological and clinical features of primary mediastinal
      large B-cell lymphoma (PMLBCL). MATERIAL AND METHODS: We analysed the results of
      biopsy material study and treatment of 86 PMLBCL patients, effects of different
      factors on the disease prognosis, efficacy of some therapeutic programs and
      overall therapeutic efficacy. RESULTS: PMLBCL manifests mainly with massive
      lesions of anterior upper mediastinum with involvement of adjacent organs and
      tissues, absence of bone marrow involvement, frequent affection of CNS. Many
      primary patients have resistance to treatment, sensitive patients have no late
      recurrences. CONCLUSION: PMLBCL is an independent extranodal variant of non
      Hodgkin's lymphoma with special clinical and morphoimmunological characteristics.
      Criteria are proposed for differential diagnosis of different variants of PMLBCL.
      New approaches to PMLBSL patients' management are outlined.

PMID- 21894751
TI  - [Differential diagnosis of thymic hyperplasia and mediastinal tumor in patients
      with lymphogranulomatosis after chemotherapy].
AB  - AIM: To make differential diagnosis of thymic hyperplasia and mediastinal tumor
      after chemotherapy (CT) in patients with Hodgkin's disease (HD). MATERIAL AND
      METHODS: The examination of 182 HD patients aged 16-71 years (median 28 years)
      included chest x-ray computed tomography (XCT) at baseline, during treatment,
      each 3 months, ultrasound investigation of the chest and abdominal cavity. All
      the patients received 6-8 courses of the treatment according to the program
      BEACOPP-14 followed by radiotherapy on the residual tumor in 137 patients, or not
      followed in 45patients. RESULTS: Soft tissue tumor in the anterior mediastinum
      was detected in 14 (31%) from 45 unirradiated patients (age 19-31 years, median
      24 years) 1 to 10 months (median 3.5 months) after chemotherapy. The analysis of
      the data of ultrasound investigation and tomography identified a mediastinal
      lesion as thymic hyperplasia. The patients are now in remission with follow-up
      median 21 months (13-36 months). No recurrence was registered. CONCLUSION: Young
      HD patients with unirradiated mediastinum develop thymic hyperplasia in 31% cases
      within one year after chemotherapy. In view of this, detection of the lesion in
      the anterior mediastinum after CT demands complex examination for differential
      diagnosis of thymic hyperplasia with tumor recurrence to avoid unwanted
      intensification of the treatment.

PMID- 21894752
TI  - [Optimization of mobilization regimes of blood hemopoietic stem cells in patients
      with multiple myeloma].
AB  - AIM: To determine an optimal cyclophosphamide dose in the mobilization scheme
      providing adequate collection of CD34+ cells in patients with multiple myeloma
      (MM), to optimize the time of initiation of granulocytic colony-stimulating
      factor (G-CSF) administration, to study effects of induction therapy schemes on
      results of mobilization and collection of CD34+ cells. MATERIAL AND METHODS:
      Department of hemoblastoses chemotherapy and bone marrow transplantation of the
      Russian Hematological Center performed mobilization of autologous blood
      hemopoietic stem cells (BHSC) in 93 MM patients treated in 2001-2010. This was
      done with cyclophosphamide and G-CSF. The former was used in 59 cases in a dose 6
      g/m2, in 34 cases - 4 g/m2. RESULTS: Myelotoxic agranulocytosis after
      cyclophosphamide administration developed in all the patients and was observed
      for 3-10 days (median 5 days). Agranulocytosis ran without documented infections
      in 51 (54.8%) patients, with febril fever - in 42 (45.2%) patients. Cepticemia,
      pneumonia, necrotic enteropathy, stomatitis, herpetic lesion of the skin were
      registered in 9, 4, 11, 14 and 6 cases, respectively. Severe thrombocytopenia (<
      30 x 10(9)/l) occurred more frequently in administration of 6 g/m2
      cyclophosphamide. It was corrected with 2-5 transfusions of thromboconcentrates,
      only 1 transfusion was needed after the dose 4 g/m2. Collection of CD34+ cells
      started in leukocyte level over 3.5 x 10(9)/l on mobilization day 12-20 (median
      day 15). The day of the first leukocytapheresis did not depend on the day of the
      first introduction of G-CSF. Duration of G-CSF administration was significantly
      shorter in the start of its use after leukocyte count decrease under 1.0 x
      10(9)/l. Conduction of 1 to S (median 2) leukocytapheresis was needed for
      collection of BHSC. Sufficient for 2 autotransplantations number of BHSC were
      stored in 90 of 93 patients. Cyclophosphamide administration in a dose 6 g/m2
      allowed collection of cells sufficient for one autotransplantation for the first
      leukapheresis in 52 (88.1) patients. A total number of CD34+ cells over 4 x 10(6)
      cells/kg were collected in 56 (94.9%) patients. In administration of
      cyclophosphamide in a dose 4 g/m2 mobilization was effective in all 34 patients.
      The first leukapheresis provided sufficient for one autotransplantation number of
      cells in 29 (85.3%) patients. CONCLUSION: Administration of high cyclophosphamide
      doses in combination with G-CSF is an effective and safe method of BHSC
      mobilization providing collection of adequate number of CD34+ cells for double
      autotransplantation in 96.8% patients. Cost effective is the start of G-CSF
      administration in the fall of leukocytes under 1.0 x 10(9)/l. Cyclophosphamide
      dose 4 g/m2 provides collection of CD34+ cells number sufficient for two
      autotransplantations in moderate thrombocytopenia and in less number of
      substitute transfusions in the absence of serious toxic complications.

PMID- 21894753
TI  - [An extremely high serum methotrexate concentration associated with acute renal
      failure in a patient with acute lymphoblastic leukemia after conduction of high
      dose consolidation].
AB  - Acute renal failure (ARF) is one of rare and severe methotrexate (MT)-induced
      complications in patients with acute lymphoblastic leukemia. A case of MT-induced
      renal dysfunction with an extremely high serum MT concentration is reported. This
      toxicity required conduction of hemodiafiltration for extracorporeal MT
      elimination. The presence of homozygous mutation of methylene-tetrahydrofolate
      reductase reflects an individual metabolism of MT and its renal clearance.

PMID- 21894754
TI  - [A case of legionellesis pneumonia verified by isolation of Legionella
      pneumophila serogroup 1 from bronchoalveolar lavage fluid treated with
      levofloxacine and tigecycline].
AB  - A male patient received non-chemotherapeutic drugs which induced deep neutropenia
      complicated with sepsis, bilateral pneumonia, acute respiratory insufficiency.
      Artificial pulmonary ventilation was applied. The examination of bronchoalveolar
      lavage showed the presence of the culture L. pneumophila (serogroup 1) in a
      concentration 2 x 10(3) CFU/ml. Antibacterial therapy with levofloxacin in a dose
      1000 mg/day was conducted. In a week not only L.pneumophila but also
      Acinetobacter baumanii was isolated from bronchoalveolar lavage. Tigecyclin was
      added to levofloxacin treatment. Two air cavities were found in the left lung.
      The treatment reduced the size of these cavities, infiltrative changes in the
      lungs and respiratory insufficiency regressed. The patient was discharged from
      hospital This case is the first case in Russia of L.pneumophila isolation from
      bronchoalveolar lavage. The case is also characterized by use of tigecycline for
      treatment of combined legionella and akinetobacterial infection and cavities in
      the lungs in legionella pneumonia.

PMID- 21894755
TI  - [Nephropathy caused by non-amyloid organized and granular deposits as multiple
      myeloma syndrome].
AB  - A rare variant of nephropathy in multiple myeloma (MM) is reported. Nephropathy
      is characterized basing on the study of nephrobiopsy with light,
      immunofluorescent and electron microscopy. A repeat biopsy of the kidney was made
      after achievement of a complete clinicohematological remission. A MM patient's
      nephrobiopsy in a picture of glomerulonephritis had 3 types of deposits:
      granular, irregular fibrils of 12 nm in diameter and microtubes organized in
      bunches 19 nm in diameter. Congo red test was negative, cryoglobulinemia was
      absent. Immunofluorescent test detected deposit of monoclonal IgG in the
      mesangium and glomerular basal membrane (GBM) corresponding to monoclonal type of
      monoclonal secretion. After treatment and achievement of remission, neither IgG
      no light chains were found in nephrobiopsy. Electron microscopy registered
      complete resorption of granular deposits and microtubes with formation of
      electron-transparent cavities. However, fibrils seen before treatment only in
      mesangium appeared in the above hollow cavities. The presence of such fibrils in
      the mesangium and GBM did not influence clinical picture of the disease. After
      achievement of remission the patient had no clinical and laboratory signs of
      nephropathy, only insignificant selective glomerular proteinurea was observed
      (0,5 g/l). Thus, granular deposits and microtubes contained paraprotein, they
      were completely resorbed after achievement of MM remission. Fibrils seem to have
      another genesis unrelated to monoclonal gammapathy.

PMID- 21894756
TI  - [Hematological disorders in celiac disease].
AB  - Gluten-sensitive celiac disease (GSCD) belongs to systemic diseases one of
      manifestations of which may be various hematological disorders. Some patients
      with GSCD have blood changes, anemia in particular, which precede clinical
      symptoms of celiac disease. Anemia can arise as a result of disorders in iron,
      folic acid and/or vitamin B12 absorption. Celiac disease can be associated with
      thrombocytosis, thrombocytopenia, leucopenia, vein thrombosis, hyposplenism,
      immunoglobulin A deficiency. Patients with celiac disease have a high risk of
      lymphoma, especially of T-cell lymphoma associated with enteropathy, B-cell non
      Hodgkin's lymphoma. Aglutenic diet, recovery of structure and function of the
      small intestine eliminate or attenuate hematological disorders associated with
      GSCD.

PMID- 21894757
TI  - [State of the endothelium and hemostasis in acute leukemia].
AB  - The review presents modern conceptions of disturbances in endothelial lining of
      the vessels and plasmic hemostasis in patients with acute leukemia; different
      mechanisms of coagulation disorders in acute leukemia: effects of leukemic cells
      containing procoagulants, fibrinolytic and antifibrinolytic substances, of
      intensive chemotherapy and inflammation. All these impacts impair endothelial
      cells and trigger plasmic coagulation cascade; the initiator of coagulation is a
      tissue factor. Mechanisms of this process and statistics of thrombohemorrhagic
      complications in different variants of acute leukemia are outlined.

PMID- 21894758
TI  - [Reforms of practical medicine in the period of the first scientific revolutions
      (the XVII century - 70-ies of XVIII century). Communication 1. Therapeutic
      diagnostic Galen's conception and failure of its practical use].
AB  - This communication outlines basic principles of Galen's therapeutic and
      diagnostic conception which dominated in medicine for 15 centuries, shows changes
      in the attitude of medical professionals to this conception as a result of
      discoveries of the first scientific revolution. Two leading trends in reforms of
      practical medicine in the XVII century are described.

PMID- 21894759
TI  - [Significance of CRF and dopamine receptors in amygdala for reinforcing effects
      of opiates and opioids on self-stimulation of lateral hypothalamus in rats].
AB  - Bipolar electrodes were implanted in the lateral hypothalamus in a group of 44
      Wistar male rats in order to study self-stimulation reaction in the Skinner box.
      Simultaneously, microcanules were implanted into the central nucleus of the
      amygdala to inject the drugs (1 microl per injection). The blockade of
      corticoliberin (CRF) receptors (astressin, 1 microg) or Na+influx currents
      (xycaine or lidocain 1 microg) by the intrastructural administration of drugs
      into the amygdala decreased self-stimulation reaction of the lateral hypothalamus
      in rats by 29-55%. The inhibition of D1 and D2 dopamine receptors in the amygdala
      with SCH23390 (1 microg) or sulpiride (1 microg) respectively, also reduced self
      stimulation but to a lower degree. On the background of blockade of CRF
      (astressin) and dopamine (sulpiride) receptors as well as sodium influx ionic
      currents (lidocain) in the amygdala neurons, psychomotor stimulant amphetamine (1
      mg/kg) and barbiturate sodium ethaminal (5 mg/kg) retained their psychoactivating
      effect on self-stimulation (+30-37%), while fentanyl (0.1 mg/kg) and leu
      enkephaline (0.1 mg/kg) did not produce this effect. Fentanyl moderately
      activated self-stimulation only after the blockade of D1 dopamine receptors with
      SCH23390. After the blockade of CRF receptors, leu-enkephaline strengthened its
      depressant effect on self-stimulation reaction (-89%). Therefore, if the
      modulating action of amygdala on the hypothalamus is eliminated, the enhancing
      effects of opiates (fentanyl) and opioids (leu-encephaline) are blocked, but the
      effects of psychomotor stimulant amphetamine and barbiturate sodium ethaminal are
      retained.

PMID- 21894760
TI  - [Comparative study of amantadine and hemantane effects on development of levodopa
      induced dyskinesia in rat model of parkinsonian syndrome].
AB  - Chronic administration of levodopa and benserazide (10 and 15 mg/kg,
      respectively) cause the development of dyskinesia in rats with model parkinsonian
      syndrome induced by injection of 6-hydroxydopamine in left substantia nigra. The
      chronic administration of these drugs together with amantadine (20 mg/kg)
      accelerates the onset of latency and increases the magnitude of dyskinesia.
      Chronic administration of levodopa and benserazide together with hemantane (10
      mg/kg) slows down the development and decreases the magnitude of levodopa-induced
      abnormal involuntary movements as measured for limb, orolingual and rotatory
      movements.

PMID- 21894761
TI  - [Efficiency of etoxidol in treating cardiovascular disorders caused by
      experimental cerebral ischemia].
AB  - A complex pharmacological study of the new cytoprotector drug etoksidol in
      animals with the disturbances of cerebral blood circulation showed that the
      intravenous introduction of the drug restores autonomous nomotopic driver of
      rhythm, conductivity in the atria and atrioventricular connection, and
      refractoriness of the atrioventricular connection, which were violated a result
      of sharp cerebral ischemia. The new drug does not suppress the inotropic function
      of the heart in cats and limits the dimensions of the zone of necrosis in rats
      with the myocardial infarction on the background of deficiency of the cerebral
      blood flow.

PMID- 21894762
TI  - [Comparison of stress protector activity of drugs with antioxidant activity
      (vitamin E, dimephosphon, reamberin) in rats].
AB  - The condition of the mucous membrane and lipid spectrum of tissue structures
      under the action of gastric ulcerogenic stress factors was studied on the
      background of administration of vitamin E, dimephosphon, and reamberin. The use
      of antioxidants, especially reamberin, led to the restoration of lipid metabolism
      and normalization of lipid peroxidation processes.

PMID- 21894763
TI  - [Effects of flaxseed extract on rheological properties of blood in experimental
      ovariectomy].
AB  - The effect of flaxseed extract (FSE) containing 42% secoisolariciresinol
      diglucoside on the blood plasma estradiol level and theological properties of
      blood in female Wistar rats after ovariectomy was investigated by measuring
      hematocrit, fibrinogen concentration, platelet aggregation and deformability, and
      the whole blood and plasma viscosity. Bilateral ovariectomy in rats led (in
      comparison to sham-operated animals) to a decrease in the estrogen level to 59%
      and produced a 5-9% increase in the whole blood viscosity, which was caused by
      impairment of the erythrocyte deformability and aggregation. The efficacy of
      oxygen transport to tissues was decreased by 4-7%. The treatment of
      ovariectomized rats with FSE (peroral administration at a daily dose of 40 mg/kg
      for 14 days) reduced the whole blood viscosity by 4-11% and increased the
      coefficient of oxygen transport to tissues by 5-11%, but did not restore the
      estrogen level. Thus, the hemorheological effect of FSE reduces to the
      improvement of microrheological parameters (decrease in erythrocyte aggregation
      and increase in their deformability) without the modification ofmacrorheological
      parameters (hematocrit, plasma viscosity and fibrinogen level).

PMID- 21894764
TI  - [Pharmacokinetics of afobazole metabolite (M-11) in rats].
AB  - Pharmacokinetics of compound M-11 (main metabolite of afobazole) after
      administration via different routes was studied in rats. After oral and
      intravenous administration, M-11 exhibited weakly pronounced bioconversion with
      the formation of a few metabolites that could be detected in plasma samples for
      about 3 hours. The absolute bioavailability of M-11 after oral administration was
      68.3%. It was found that M-11 was completely absorbed from gastrointestinal tract
      of rats and characterized by "the first pass effect", after which approximately
      70% of administered dose entered the circulation. The parent substance was
      determined neither in urine nor in feces.

PMID- 21894765
TI  - [Main pharmacokinetic parameters of p-tyrosol after intravenous injection in
      rats. Part III: Distribution of p-tyrosol in rat].
AB  - Distribution of p-tyrosol in organism was studied in rats after a single
      intravenous administration in a dose of 200 mg/kg. It was shown that p-tyrosol
      rapidly penetrates into well perfused organs (brain, heart, kidneys). The maximum
      concentration ofp-tyrosol in these organs was determined in 1 minute after
      administration, and the mean distribution constant was within 0.8-1.11. The
      albumin bound fraction ofp-tyrozol amounted to 0.26-0.30.

PMID- 21894766
TI  - [Antioxidant properties of some sulfur-containing substances].
AB  - The antioxidant properties of sulfur-containing substances have been
      experimentally studied in vitro. Unithiol exhibits a wide spectrum us radicals.
      For this reason, unithiol can be considered, along with ascorbic acid, as a
      universal drug for the reduction of free radical reactions.

PMID- 21894768
TI  - [Comparative pharmacokinetics of antigrippin-maximum administered in capsules and
      powder for preparing solutions].
AB  - Comparative pharmacokinetics of anti-influenza drug composition Antigrippin
      maximum administered in capsules and a powder for preparing solutions has been
      studied after single administraton in a group of 18 healthy volunteers. Both
      preparations [manufactured by the Antiviral Research and Production Corporation
      (St Petersbutg) contain 6 active components, including paracetamol, rimantadine,
      loratadine, ascorbic acid, calcium gluconate, and rutoside in equal amounts. The
      concentrations of unchanged paracetamol, rimantadine, and loratadine in the blood
      plasma were degtermined by HPLC with mass-spectrometric and UV detection. The
      pharmacokinetic parameters of allindicated active components exhibited no
      detectable distinctions, except for the time to attaining maximum concentration
      ofparacetamol and the value of the maximum concentration of loratadine.

PMID- 21894767
TI  - [Positive effect of cytoflavin on metabolic status changes in patients with burn
      disorder].
AB  - Complex clinical and laboratory examination of 60 patients with moderate level of
      burn damage included determination of the content of intermediate products of
      lipid peroxidation (LPO) (malonic dialdehyde, diene conjugate, SH groups and
      tocopherol) in blood and peripheral zone of the skin and hypodermic tissue. At
      the same time, the activity of superoxide distumase (SOD) and catalase was
      evaluated. This examination was performed on the first and third days after
      injury, in the period of burn shock. In the course of conventional therapy, burn
      shock was characterized by LPO intensification and insufficiency of the blood
      antioxidant system. Cytoflavin included into the conventional therapy produces
      improvement in metabolic changes due to the activation of blood SOD and catalase
      and an increase in tocopherol (vitaminE) content in the blood.

PMID- 21894769
TI  - [Melatoninergic antidepressant valdoxan].
AB  - Data on the pharmacological properties, mechanism of action, and clinical
      advantages of the new antidepressant drug valdoxan capable of selectively
      stimulating melatonin receptors are presented. The drug effect is compared to the
      action of epiphyseal hormone melatonin and traditional antidepressants.

PMID- 21894770
TI  - [A cross-sectional study of the current status of respiratory home care patients
      and their caregivers in Osaka Prefecture].
AB  - BACKGROUND: The importance of the home care of patients with chronic respiratory
      failure has been emphasized, but the status of the patients and their caregivers
      have not been comprehensively evaluated. METHODS: We performed a cross-sectional
      analysis of 242 patients treated at home with long-term oxygen therapy (LTOT)
      and/ or non-invasive positive pressure ventilation (NPPV) and of their
      caregivers, using a questionnaire survey. RESULTS: A total of 176 patients
      responded. The patients' mean age was 74.5 years, and 80.7%, 16.5%, and 1.7% of
      them were treated with LTOT, LTOT and NPPV, and NPPV, respectively. Of these, 29
      patients lived alone, and 11 of whom had no caregivers. The SF-8 questionnaire, a
      health-related quality of life (HRQOL) scale, showed that the patients' HRQOL was
      lower than the Japanese standard. Patients with severe dyspnea were not all
      designated as requiring a high care level according to the Long-Term Care
      Insurance System. A total of 155 caregivers responded to the questionnaire, and
      their mean age was 64.7 years; 81% of them were women and 67.7% were the
      patients' spouses. The Burden Index of Caregivers (BIC-11), which is a
      multidimensional short care burden scale, showed that they bore the burden of
      patient care, comparable to the caregivers of patients with intractable
      neurological diseases. The patients and their caregivers required several
      services including a family doctor, public aid, and short-term hospitalization.
      CONCLUSIONS: This study highlighted the poor HRQOL of patients provided with LTOT
      and/or NPPV, and the considerable burden on their caregivers. Current respiratory
      home care should be reviewed thoroughly, and further measures to support the
      patients and their caregivers should be implemented.

PMID- 21894771
TI  - [Multidisciplinary assessment of effects, safety and procedure of whole lung
      lavage for 8 patients with autoimmune pulmonary alveolar proteinosis].
AB  - We treated 8 cases of autoimmune pulmonary alveolar proteinosis (APAP) with whole
      lung lavage (WLL) in our hospital and evaluated the disease severity of APAP
      before and after WLL, adverse events (AEs) and recurrence-free survival in those
      cases who improved. In all cases, unilateral WLL was performed in both lungs. The
      median of total lavage volume in unilateral WLL was 17.9 L, and the median
      procedure time of unilateral WLL was 105 min. Fever was the most frequently
      observed AE (87.5% of all procedures). Pulmonary function tests (percentage of
      predicted value of VC, FEV1 and diffusing capacity of carbon monoxide), serum
      markers (KL-6, surfactant apoprotein (SP)-D, SP-A and carcinoembryonic antigens),
      arterial blood gas analyses (PaO2, AaDO2) and disease severity score all
      significantly improved after WLL. The serum levels of anti-granulocyte-macrophage
      colony-stimulating factor (GM-CSF) antibody temporarily decreased after
      unilateral WLL, but returned to previous levels (before WLL) in 7 cases. The
      radiological findings improved in 6 cases. In the 7 improved cases in whom AaDO2
      decreased more than 10 Torr, the median recurrence-free survival of APAP after
      WLL was 17.5 months. We concluded that WLL is an effective and safe method for
      the treatment of APAP, and all parameters except for anti GM-CSF antibody are
      useful to evaluate the effect of WLL.

PMID- 21894772
TI  - [A case of pulmonary carcinomatous lymphangitis and multiple pulmonary
      infarctions from gastric cancer].
AB  - We report a case of pulmonary carcinomatous lymphangitis and multiple pulmonary
      infarctions from gastric cancer. A 58-year-old housewife presented with a
      complaint of a worsening cough over the previous 6 weeks. Chest radiography and
      CT scans revealed infiltration and diffuse ground-glass opacities in both lung
      fields, and she was hospitalized for further examination. No specific findings
      were found upon screening examination, including bronchoscopy with
      bronchoalveolar lavage (BAL). However, a CT scan showed mediastinal, hilar and
      paraaortic lymph node swelling, and therefore we suspected the presence of a
      malignant tumor. On the 11th hospital day, she suddenly developed severe hypoxia
      and went into cardiogenic shock. Although there was no sign of a filling defect
      in the vessels on CT with an intravenous contrast, we diagnosed pulmonary
      thromboembolism based on other examination findings and began thrombolysis and
      anticoagulant therapy. Treatment with heparin and urokinase did not improve her
      condition, and she died on the 14th hospital day. The autopsy findings revealed
      widespread gastric cancer with pulmonary lymphangitis carcinomatosa and thrombus
      formation in arterioles throughout the pulmonary lobes: 'Trousseau syndrome'.

PMID- 21894773
TI  - [A case of Mycobacterium avium pleuritis and pneumothorax in a rheumatoid
      arthritis patient treated with a TNF-alpha antagonist].
AB  - A 70-year-old woman with rheumatoid arthritis received treatment with
      corticosteroids and methotrexate for 4 years, followed by an additional TNF-alpha
      antagonist (infliximab) for about 3 years. She presented with a several-week
      history of persistent cough, and CT images of the lung showed a thin-walled
      cavitary lesion abutting the pleural surface of the left upper lobe. While we
      investigated the cause of this lesion, we admitted her because of acute chest
      pain. Chest radiography demonstrated moderate left-sided pneumothorax with
      pleural effusion. After further investigation, we suspected that her pneumothorax
      and pleuritis had been caused by a ruptured cavitary lesion arising from a
      Mycobacterium avium infection. Despite multi-drug therapy, chest tube drainage
      and surgical pulmorrhaphy her pleural complications were intractable. This is a
      rare case of pneumothorax and pleuritis caused by Mycobacterium avium infection
      induced by a TNF-alpha antagonist. Physicians should be aware of nontuberculous
      mycobacterial infections in patients treated with TNF-alpha antagonists.

PMID- 21894774
TI  - [A case of acute mediastinitis after endobronchial needle aspiration].
AB  - BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration
      (EBUS-TBNA) has become widespread, but reports of complications are rare. CASE:
      An enlarged mediastinal lymph node (4R) was detected in a 67-year-old man 33
      months after surgery for rectal cancer, and we performed EBUS-TBNA to confirm the
      diagnosis. He was then admitted to hospital 13 days after the procedure, with
      cough, a swollen mediastinal fatty area around the 4R lymph node, and elevated
      WBC and CRP levels. After a diagnosis of acute mediastinitis was confirmed we
      gave him antibiotics, which improved his symptoms, the mediastinal fatty area and
      his WBC and CRP levels. CONCLUSION: We have to be aware of the possibility of
      acute mediastinitis after EBUS-TBNA of necrotic lymph nodes.

PMID- 21894775
TI  - [A case of pulmonary nocardiosis due to Nocardia cyriacigeorgica with prompt
      diagnosis by gram stain].
AB  - An 82-year-old woman with a past history of a colectomy for colon cancer was
      admitted to our hospital because of fever and cough. Her chest radiologic images
      on admission showed bilateral pulmonary infiltration, which suggested community
      acquired pneumonia. However, the results of gram and acid-fast staining
      demonstrated branching acid-bacilli, which suggested pulmonary nocardiosis. We
      administered sulfamethoxazole-trimethoprim, and her condition and radiology
      findings promptly improved. Nocardia cyriacigeorgica was identified from her
      sputum. One of the nocardial isolates, formerly identified as Nocardia
      asteroides, has recently been reclassified as Nocardia cyriacigeorgica by the 16S
      rRNA gene amplification method. Pulmonary nocardiosis may be misidentified as
      "aspiration pneumonia", especially in elderly people. It is important for
      patients with community-acquired pneumonia to be evaluated with sputum gram
      staining for accurate diagnosis.

PMID- 21894776
TI  - [Methotrexate-related lymphomatoid granulomatosis in a patient with rheumatoid
      arthritis].
AB  - A 76-year-old man who was taking prednisolone and methotrexate for rheumatoid
      arthritis presented with gastric ulcers. Chest X-ray images showed multiple
      pulmonary nodules. Transbronchial lung biopsy specimens showed lymphocytic
      infiltrates but no malignant cells. The radiographic findings gradually
      ameliorated over a month, but then deteriorated 5 months later. We performed
      video-assisted thoracoscopic biopsy of the left lung, and the biopsy specimens
      showed lymphocytic infiltration with necrosis, in which the atypical lymphocytes
      were positive for Epstein-Barr virus-encoded small RNAs in situ hybridization
      (EBER-ISH). A diagnosis of lymphomatoid granulomatosis was determined. One year
      before this diagnosis, the patient was found to have an inflammatory liver tumor
      that had disappeared spontaneously within a month. A new pathological review of
      the liver and stomach lesions demonstrated EBER-ISH-positive lymphocytes, and
      therefore we assumed that they were pathological features of lymphomatoid
      granulomatosis. The chest radiographic findings improved gradually after the
      discontinuation of methotrexate. We therefore suggest that methotrexate treatment
      may be associated with the development of lymphomatoid granulomatosis in patients
      with rheumatoid arthritis. Lymphoproliferative disorders, including lymphomatoid
      granulomatosis, should be considered in patients with rheumatoid arthritis who
      are receiving methotrexate.

PMID- 21894777
TI  - [A case of small-cell lung cancer associated with paraneoplastic limbic
      encephalitis during chemotherapy].
AB  - A 75-year-old woman received a diagnosis of small-cell lung cancer (T1N2M0, stage
      IIIA, limited disease) in January 2009. She received 4 cycles of chemotherapy
      with etoposide and carboplatin and concurrent radiotherapy (50 Gy/25 Fr) which
      yielded a complete response. However, recurrence of her small-cell lung cancer
      occurred in a mediastinal lymph node and the ribs in November 2009. During the
      2nd cycle of second-line chemotherapy with nogitecan, she was readmitted to our
      hospital complaining of amnesia, periods of unconsciousness and convulsions. Her
      laboratory data on admission revealed normal serum electrolyte and cerebrospinal
      fluid levels, and electroencephalogram findings. Her neurological symptoms, which
      mimicked limbic encephalitis improved after steroid pulse therapy plus third-line
      chemotherapy with amrubicin. The final diagnosis was paraneoplastic limbic
      encephalitis by positive serum voltage-gated calcium channel antibodies. We
      hereby report a rare case of small-cell lung cancer associated with
      paraneoplastic limbic encephalitis during chemotherapy.

PMID- 21894778
TI  - [A case of mild pulmonary tuberculosis complicated with the syndrome of
      inappropriate antidiuretic hormone secretion which caused impaired
      consciousness].
AB  - An 81-year-old woman was admitted to our hospital for hyponatremia and impaired
      consciousness after unsuccessful antibiotic treatment for pneumonia-like symptoms
      by a previous doctor. A chest X-ray film revealed unilateral infiltration.
      Mycobacterium tuberculosis was detected on a sputum smear and pulmonary
      tuberculosis was diagnosed. Based on the diagnostic criteria, we believed that
      her hyponatremia a consequence of syndrome of inappropriate antidiuretic hormone
      secretion (SIADH) as a complication of pulmonary tuberculosis. Sodium loading and
      water restriction quickly improved her serum sodium level and impaired
      consciousness. Anti-tuberculosis therapy reduced the abnormal shadows noted on
      chest X-ray films, and the sputum smear became negative for Mycobacterium
      tuberculosis. Her serum sodium level remained normal after the discontinuation of
      sodium loading. Previous reports have associated SIADH with severe types of
      tuberculosis such as miliary tuberculosis, tuberculosis meningitis, and pulmonary
      tuberculosis with massive bacterial excretion. However, this complication can
      also occur in mild tuberculosis, as in this case, thus SIADH should also be
      considered in mild cases of tuberculosis.

PMID- 21894779
TI  - [Allergic bronchopulmonary mycosis due to Schizophyllum commune and Aspergillus
      fumigatus].
AB  - A 53-year-old man who had been suffering from asthma presented to our hospital
      because of abnormal shadows detected on a chest X-ray film during a routine
      medical examination. A biopsy specimen of a mucus plug obtained by bronchoscopy
      showed fungal hyphae, eosinophils, and Charcot-Leyden crystals, with evidence of
      lung tissue eosinophilia. Schizophyllum commune and Aspergillus fumigatus were
      isolated from his sputum, bronchial washing specimens and the mucus plug. We
      detected specific immunoglobulin E anti-Aspergillus fumigatus responses and
      precipitating antibodies against Schizophyllum commune and Aspergillus fumigatus,
      which led to the diagnosis of allergic bronchopulmonary mycosis caused by both
      fungi. We gave him fluticasone/salmeterol and itraconazole; thereafter, his
      symptoms of cough and sputum production and his radiological findings all
      improved.

PMID- 21894780
TI  - [A case of pulmonary varices demonstrated by three-dimensional computed
      tomography].
AB  - We present a case of pulmonary varices in a 44-year-old man. The patient's chest
      X-ray films revealed well-delineated shadows in the right lower lung field. An
      enhanced chest CT scan with three-dimensional volumetric imaging demonstrated a
      vascular malformation in the right lower lobe. Both the arterial and parenchymal
      phases of digital subtraction of the right pulmonary angiography were normal.
      However, the venous phase showed serpiginous right lower pulmonary veins draining
      into the left atrium, and a delayed pooling of contrast in dilated pulmonary
      veins confirmed a diagnosis of pulmonary varices. No echocardiographic findings
      of valvular disease were recognized. He remained asymptomatic and returned to
      work, but radiological follow-up was continued annually.

PMID- 21894781
TI  - Reaching out to neglected children.

PMID- 21894782
TI  - Plenty of money for nurses' pay.

PMID- 21894783
TI  - Plenty of money for nurses' pay.

PMID- 21894784
TI  - District nurses--an innovative and flexible workforce.

PMID- 21894785
TI  - Encouraging family-centred care in neonatal practice.

PMID- 21894786
TI  - Matariki in parliament.

PMID- 21894787
TI  - Supporting premature and sick infants in Samoa.

PMID- 21894788
TI  - Neonatal nursing--an exciting world of practice.

PMID- 21894789
TI  - The value of combined nursing and midwifery skills.

PMID- 21894790
TI  - Wound healing--repair at the expense of function.

PMID- 21894791
TI  - When is bullying not bullying?

PMID- 21894792
TI  - Sleeping on the job.

PMID- 21894793
TI  - How poverty hurts our children.

PMID- 21894795
TI  - QRS duration and QTc interval are predictors of risk for ventricular arrhythmias
      during cardiac resynchronization therapy.
AB  - BACKGROUND AND OBJECTIVES: QRS duration (QRSd) and prolonged corrected QT
      interval (QTc) are associated with ventricular arrhythmic events. This study was
      designed to determine whether CRT by means of biventricular pacing alters the QTc
      and QRSd, and whether such changes are related to the risk of sustained
      ventricular tachyarrhythmias (sVTA). METHODS AND RESULTS: A total of 127 patients
      (102 men, mean age 63.9 +/- 8.9 years) with drug-resistant heart failure and QRS
      duration > or = 130 ms underwent CRT/CRT-ICD. The aetiology of the heart failure
      was ischaemic in 41 patients (32.3%). After a median follow-up of 24 months, 42
      sVTA occurred in 35 patients (27.6%). Twenty-nine patients had a single sVTA, in
      five patients two sVTA and in one patient three sVTA occurred. The paced QTc was
      longer in sVTA patients (505 +/- 55 ms) compared with no sVTA patients (486 +/-
      44 ms, P < or = 0.003). Similar responses for paced QRSd were observed (182 +/-
      27 ms in sVTA patients vs 167 +/- 27 ms in no-sVTA patients, P < or = 0.03). This
      effect was independent from intrinsic QTc and QRSd and the aetiology of the heart
      failure. The mortality rate was significantly higher in patients with ventricular
      fibrillation and fast VT (P < or = 0.004) who experienced shock therapies.
      However, the sVTA were not the immediate cause of death. CONCLUSIONS: A pacing
      induced increase in QTc and QRSd is related to sVTA in patients with CRT. Further
      studies are needed to determine whether optimization of CRT with the goal to
      achieve a narrow paced QRSd can reduce the occurrence of sVTA.

PMID- 21894794
TI  - The CAREGENE study: genetic variants of the endothelium and aerobic power in
      patients with coronary artery disease.
AB  - OBJECTIVES: Aerobic phenotypes show a wide variability to similar aerobic
      training stimuli, which can be partly attributed to heritability. Endothelial
      function affects aerobic power. Various physiological pathways may influence the
      endothelial function. Therefore, we aimed to examine whether polymorphisms of the
      eNos gene, the CAT gene, the VEGF gene, the GPX1 gene, the subunit P22 phox of
      the NAD(P)H-odixase gene, the PPAR-alpha gene, and the PGC-alpha gene are
      associated with aerobic power or with its response to physical training in
      patients with coronary artery disease (CAD). METHODS: 935 biologically unrelated
      Caucasian patients with CAD who had exercised until exhaustion during graded
      bicycle testing at baseline and after completion of 3 months of training were
      included in the CAREGENE study (Cardiac Rehabilitation and GENetics of exercise
      performance). Polymorphisms were detected using the invader assay and MassARRAY
      technology. Haplotype analysis was performed on the polymorphisms of the eNos
      gene, the VEGF gene and the NAD(P)H-oxidase gene. RESULTS: Physical training
      significantly increased aerobic power by 24.2 +/- 0.6% (P < 0.001). Associations
      of P < 0.05 were found between aerobic power and the eNOS 273C>T variant and the
      catalase -262C>T variant and aerobic power response. Haplotypes of the eNOS
      polymorhisms were predictive of aerobic power and its response to training (P <
      0.05). After Bonferroni correction of multiple testing no significant differences
      remained. CONCLUSION: We believe that genetic factors are very important in the
      explanation of the great variability of aerobic power and its response. However,
      after Bonferroni-correction, differences in these polymorphisms remained no
      longer statistically significant.

PMID- 21894796
TI  - Low safety index of domperidone: mechanism for increased odds ratio for sudden
      cardiac death.
AB  - OBJECTIVE: Domperidone is a dopamine antagonist with anti-nausea and anti-emetic
      activity. There have been several reports of sudden cardiac death (SCD)
      associated with the compound. Recently it was estimated to increase SCD nearly
      fourfold. I therefore tested domperidone for liability of cardiac repolarization
      disturbances (triangulation, reverse use dependence, instability and dispersion
      or TRIaD) and induction of arrhythmias. METHODS AND RESULTS: In Langendorff
      perfused rabbit hearts, domperidone significantly prolonged the action potential
      duration starting at 30 nM. It induced proarrhythmic TRIaD from 100 nM on. Since
      therapeutic free drug concentrations extend to 19 nM, the safety ratio for
      domperidone equals 100/19 = 5.25, i.e., far below the minimum safety ratio of 30.
      Hence, widespread use of domperidone cannot be without danger; especially since
      it is frequently used as an over the counter medication. CONCLUSION: In light of
      these new preclinical and of recent clinical warnings, domperidone should best be
      restricted to patients in whom its benefit is proven to justify the risks.
      Availability without prescription and advertising as an 'innocent' relief is
      incorrect and unsafe, and needs to be reconsidered.

PMID- 21894797
TI  - Cardiac injury in patients with pandemic 2009 influenza A (H1N1) infection.
AB  - BACKGROUND: In March 2009, the novel 2009 influenza A (H1N1) was first reported
      in the southwest of Mexico, and rapidly spread worldwide. We investigated the
      clinical features of cardiovascular involvement of patients infected with the
      2009 influenza A (H1N1) virus in China. METHODS: This retrospective study
      recruited one hundred and seventy-two patients with 2009 influenza A (H1N1) of
      different severity (non-severe, severe, critically severe) and 21 patients who
      were influenza A (H1N1)-negative but who had an influenza-like illness. Blood was
      obtained for measurement of the concentration of creatine kinase (CK), creatine
      kinase-MB (CK-MB) and high sensitivity C-reactive protein (hs-CRP) in plasma.
      Chest radiography was also undertaken to calculate the cardiothoracic ratio
      (CTR). RESULTS: influenza A (H1N1) caused more illness in middle-aged people. The
      patients in the non-severe group were younger than in the severe group (P < 0.05)
      and the non-influenza A (H1N1) group (P < 0.01). The level of CK, CK-MB, hs-CRP
      and the CTR was higher in the critically severe group than in the other three
      groups (P < 0.001, P < 0.05, P < 0.01, P < 0.01, respectively). CONCLUSIONS:
      Myocardial injury was quite serious in severe infection by the influenza A (H1N1)
      virus, particularly in critically severe patients. Patients with 2009 influenza A
      (H1N1) had injury and dilation of the heart, which may be a potential cause of
      death.

PMID- 21894798
TI  - Apolipoprotein B assessment for evaluating lipid goals.
AB  - OBJECTIVE: It is suggested that the apolipoprotein (Apo) B levels are more
      valuable than LDL cholesterol (LDL-C) levels in assessing cardiovascular risk
      associated with hyperlipidaemia. However, although non-HDL cholesterol (non-HDL
      C) levels are accepted as a secondary objective after achieving LDL-C levels in
      the guidelines, Apo B has not been recommended as a therapeutic goal yet. The
      objective of this study was to determine how many of the patients who achieved
      the LDL-C and non-HDL-C target recommended by the guidelines with a statin
      therapy achieved the Apo B target. METHODS: The study included a total of 182
      consecutive hypercholesterolaemic (119 male, 63 female) patients who were over 18
      years of age (mean age: 54.96 +/- 9.27 y) and on statin therapy. Apo B and non
      HDL-C levels were determined for the patients who achieved or did not achieve the
      LDL-C target according to the cardiovascular risk categories defined in the Adult
      Treatment Panel-III report. Serum Apo B levels were assessed using the
      nephelometric method. RESULTS: The prevalence of patients who achieved the LDL-C,
      non-HDL-C and Apo B target was 63.2%, 79.7% and 72.5%, respectively. All of the
      patients who achieved the LDL-C target also achieved the non-HDL-C target. It was
      found that 6 of 115 patients (5.2%) who achieved the LDL-C and non-HDL-C target
      failed to achieve the Apo B target, whereas 23 of 132 patients (17.4%) who
      achieved the Apo B target failed to achieve the LDL-C target. CONCLUSIONS: These
      results showed that 95% of patients who received a statin therapy, and achieved
      LDL-C and non-HDL-C targets also achieved the Apo B target.

PMID- 21894799
TI  - Clinical outcomes of brief versus prolonged unfractionated heparin infusion after
      primary percutaneous coronary intervention for ST-segment elevation myocardial
      infarction in the drug-eluting stent era: real-world, single-centre experience.
AB  - OBJECTIVE: Optimal dose and duration of intravenous unfractionated heparin (UFH)
      infusion after primary percutaneous coronary intervention (PCI) for ST-segment
      elevation myocardial infarction (STEMI) are unknown when glycoprotein IIb/IIIa
      inhibitors (GPIs) are not used. We evaluated the clinical outcomes in patients
      who received brief versus prolonged UFH infusion following primary PCI for STEMI
      in the era of drug-eluting stents (DES). METHODS: We studied 273 (216 men, 63 +/-
      12 years) consecutive patients who underwent primary PCI with DES implantation
      for STEMI between December 2003 and May 2009. All patients received currently
      recommended loading and maintenance doses of aspirin and clopidogrel. In-hospital
      and cumulative 30-day rates of major adverse cardiovascular events (MACEs) and
      major bleeding were compared between patients receiving brief (< 48 (26 +/- 15)
      hours, group 1) and those receiving prolonged (> or = 48 (83 +/- 38) hours, group
      2) infusion of intravenous UFH following index procedure. RESULTS: The
      demographic and baseline angiographic characteristics were similar between the
      two groups. In-hospital and cumulative 30-day MACEs rates and major bleeding
      events rates were not statistically different between groups. CONCLUSION: In this
      single-centre experience, in patients with STEMI who underwent primary PCI in the
      era of DES, a routine post-procedure course of UFH infusion for more than 48
      hours was not associated with any significant benefits. Further study is
      warranted to determine the optimal duration and dose of administration of UFH
      infusion following primary PCI.

PMID- 21894800
TI  - The preoperative cardiology consultation: goal settings and great expectations.
AB  - BACKGROUND: Despite the availability of guidelines for preoperative cardiology
      consultations, their efficacy in real clinical practice remains unknown.
      Furthermore, there are concerns that overused cardiology consultations can lead
      to unnecessary investigations, prolonged hospital stays, and even cancellation of
      necessary surgery. In this retrospective study, we investigated: (i) the
      potential impact of the American Heart Association/American College of Cardiology
      algorithm and (ii) the potential of this algorithm for preventing unnecessary
      evaluation. METHODS: We examined the cardiology consultation requests for 712
      patients scheduled for elective surgery. Our analysis included: (i) patient
      characteristics, (ii) abnormalities revealed by the consultant, (iii) impact of
      these abnormalities on clinical decision making and therapy modification.
      RESULTS: The most common reason for consultation was 'pre-operative evaluation'
      (80.9%). Although our cardiologists revealed an abnormality in 67.8% and
      recommended further work up in 58.7% of our patients, they contributed to the
      clinical course in only 36.9%. Moreover, when the algorithm was applied to
      'routine pre-operative evaluation' requests lacking a specific question, only
      7.6% of these consultation requests required further investigation. CONCLUSION:
      Preoperative cardiology consultation seems to be overused. Although the fear of
      missing important issues leads surgeons to use a decreased threshold for pre
      operative consultation requests, such a non-specific manner of pre-operative
      consultation request causes unnecessary investigations and decreased cost
      effectiveness. Furthermore, the detection of any clinical abnormality by
      cardiologists surprisingly adds little to clinical decision making.

PMID- 21894802
TI  - Standardization of the apex beat in the full left lateral position and its
      diagnostic value in detecting left ventricular dilatation.
AB  - AIMS: The aims of this study were to determine the characteristics of the apex
      beat in the full left lateral position in healthy adults, and to assess its value
      in the diagnosis of left ventricular dilatation. METHODS AND RESULTS: 77 healthy
      adults and 27 patients with left ventricular dilatation were evaluated by
      history, physical examination, electrocardiography, apexcardiography and complete
      transthoracic echocardiographic examination. The location, size and quality of
      the apex beat were determined in the 90-degree left lateral position. A palpable
      apex beat, located in the 5th or 6th intercostal space, was recorded in 87% of
      the healthy adults. The lateral margin was palpated in a 3-cm-wide area from the
      left anterior axillary line (LAAL) towards the mid-clavicular line (MCL). The
      mean diameter and area were 2.5 +/- 0.5 cm and 5.0 +/- 2.5 cm2, respectively. In
      51% the apex impulse intensity was of medium degree, in 25% weak and in 24%
      strong. It was palpable in all patients with left ventricular enlargement in the
      5th, 6th or 7th intercostal space. The lateral margin was located in a 4.5-cm
      wide area, 3.5 cm left from the LAAL to 1 cm right from it. The mean diameter and
      area were 5.0 +/- 1.0 cm and 20.0 +/- 7.0 cm2, repectively. The intensity was
      weak in 56% and medium degree in the rest. The diameter > or = 4.0 cm was
      sensitive (96%) and specific (96%) for the enlarged left ventricle. The location
      of the apex beat with the cut-off point in the LAAL was equally sensitive but
      less specific (63%) for left ventricular dilatation. CONCLUSIONS: Palpation of
      the apex beat in the full left lateral position is very suitable for detecting
      the left ventricular dilatation at bedside. The size of the apex beat appears to
      be a more reliable diagnostic sign of left ventricular dilatation than its
      location.

PMID- 21894801
TI  - Carotid stenting of asymptomatic and symptomatic carotid artery stenoses with and
      without the use of a distal embolic protection device.
AB  - OBJECTIVE: The objective of this study was to evaluate the incidence of
      symptomatic and clinically silent embolic following carotid angioplasty and stent
      placement (CAS) with and without the use of an embolic protection device (EPD).
      MATERIALS AND METHODS: Between January 2006 and April 2009, 76 patients with
      carotid stenosis underwent 79 CAS procedures (three patients had bilateral CAS).
      In this group, 44 of the 79 procedures were performed with an EPD, and 35 were
      performed without an EPD. In the EPD group, 26 treated hemispheres received pre-
      and post-operative diffusion-weighted MRI (DWI), and in the non-EPD group, 16
      treated hemispheres received pre- and post-operative DWI. RESULTS: All 79
      procedures were technically successful without significant residual stenosis. In
      the EPD group, there were three symptomatic ischaemic events (6.8%), and 4 of the
      26 (15.4%) treated hemispheres which received MRI showed new DWI lesions. In the
      non-EPD group, there was one symptomatic ischaemic event (2.9%), one mortality
      (2.9%) due to reperfusion injury with intracranial haemorrhage, and three of the
      16 (18.8%) treated hemispheres which received MRI showed new DWL lesions.
      CONCLUSIONS: The results of this retrospective analysis do not show demonstrable
      benefits of reducing new DWI lesions or major/minor ischaemic events after CAS
      with a filter protection device. Further investigations with more accurate risk
      analysis strategies remain necessary in hopes of selecting patients most likely
      to benefit from the use of an embolic protection device.

PMID- 21894803
TI  - Autonomic nervous function and baroreflex sensitivity in hypertensive diabetic
      patients.
AB  - OBJECTIVE: Little is known about how the cardiac autonomic nervous function (CAN)
      changes with gradually increasing systolic blood pressure (SBP). This study
      investigated cardiac autonomic nervous function in diabetic patients and controls
      with different grades of SBP. METHODS AND RESULTS: We measured heart rate
      variability (HRV) and spontaneous baroreflex sensitivity (BRS) by power spectral
      analysis in 118 Chinese type-2 diabetic patients and 137 age-matched controls.
      Subjects were further subdivided into 4 SBP groups. Results showed total HRV and
      BRS values were significantly lower in several diabetic SBP groups. Total HRV and
      BRS decreased with increasing SBP, with significant differences in the 140-159 mm
      Hg or 160-179 mm Hg groups compared with other groups of diabetic and control
      subjects. CONCLUSIONS: We found that HRV and BRS can reflect cardiovascular
      autonomic dysfunction of diabetes when accompanied by hypertension. In our
      selected Chinese diabetic and control subjects, HRV and BRS parameters were
      influenced by gradually increasing SBP.

PMID- 21894804
TI  - Singh's verbal autopsy questionnaire for the assessment of causes of death,
      social autopsy, tobacco autopsy and dietary autopsy, based on medical records and
      interview.
AB  - INTRODUCTION: The exact causes of death in India are not known because autopsy
      studies are difficult to conduct due to religious considerations. There are rapid
      changes in diet and lifestyle amongst social classes causing changes in the
      pattern of risk factors and mortality. In the present study, we attempt to
      develop a verbal autopsy questionnaire based on medical records and interview of
      a family member, for the assessment of causes of death, social class, tobacco
      consumption and dietary intakes among urban decedents in north India. METHODS:
      For the period 1999-2001, we studied the randomly selected records of death of
      2222 (1385 men and 837 women) decedents, aged 25-64 years, out of 3034 death
      records overall from the records at the Municipal Corporation, Moradabad.
      Families of these decedents were contacted individually to find out the causes of
      death, by scientist- administered, informed-consented, verbal autopsy
      questionnaire, completed with the help of the spouse and local treating doctor
      practicing in the appropriate health care region. Clinical data and causes of
      death were assessed by a questionnaire based on available hospital records and a
      modified WHO verbal autopsy questionnaire. Dietary intakes of the dead
      individuals were estimated by finding out the food intake of the spouse from 3
      day dietary diaries and by asking probing questions about differences in food
      intake by the decedents. Tobacco consumption of the victim was studied by a
      questionnaire administered to family members. Social classes were assessed by a
      questionnaire based on attributes of per capita income, occupation, education,
      housing and ownership of consumer luxury items in the household. The diagnoses of
      overweight and obesity were based on the new WHO and International College of
      Nutrition criteria. RESULTS: Cardiac diseases (23.4%, n = 520) including coronary
      artery disease (10%), valvular heart disease (7.2%, n = 160), diabetic heart
      disease (2.2%, n = 49), sudden cardiac death and inflammatory cardiac disease,
      each (2.0%, n = 44) were the most common causes of deaths as reported using the
      modified verbal autopsy questionnaire. Brain diseases including stroke (7.8%, n =
      175) and inflammatory brain disease were reported amongst 1.9% (n = 42)
      victims.Thus, NCDs (37.0%, n = 651); circulatory diseases (31.2%, n = 695)
      including stroke and cardiac diseases, and malignant neoplasms (5.8%, n = 131)
      emerged as the most common causes of death. Injury and accidents (14.0%, n = 313)
      including fire, falls and poisonings were also common. Miscellaneous causes of
      death were observed amongst 8.5% (n = 189) of victims. Pregnancy and perinatal
      causes (0.72%, n = 15) were not commonly recorded in our study. Renal diseases
      (11.2%, n = 250), pulmonary diseases (22.3%, n = 495) and liver diseases (4.8%, n
      =107) were also commonly recorded causes of death. It is clear that causes of
      death related to various body systems can be more accurately assessed by the
      modified verbal autopsy questionnaire. Circulatory diseases as the cause of
      mortality were significantly more common among higher social classes (1-3) than
      in lower social classes (4 and 5) who died more often, due to infections. Death
      due to coronary disease, stroke, hypertension, diabetes and obesity were
      significantly more common among higher social classes 1-3 and among victims with
      higher body mass index (BMI) compared to social class 4 and 5 who had lower BMI.
      CONCLUSIONS: This study indicates that causes of death, social class, tobacco and
      dietary intakes, can be accurately assessed by a modified verbal autopsy
      questionnaire based on medical records and by interview of family members.
      Circulatory diseases, injury-accidents and maligant diseases have become the
      major causes of death in India, apart from infections.

PMID- 21894805
TI  - Plasma thrombin-activatable fibrinolysis inhibitor levels and Thr325Ile
      polymorphism as a risk marker of myocardial infarction in Egyptian patients.
AB  - OBJECTIVE: The objective of this study was to investigate whether thrombin
      activatable fibrinolytic inhibitor (TAFI) Thr325Ile polymorphism and TAFI antigen
      (Ag) levels could constitute a risk marker of myocardial infarction (MI) in
      Egyptian patients. STUDY POPULATION AND RESULTS: The study included forty-six
      patients with acute MI (mean age 55.7 +/- 8.1 years, 33 men, 13 women) compared
      with age and sex-matched healthy volunteers (n = 54) as a control group. Clinical
      examination, laboratory investigations, electrocardiography (ECG) and/or
      echocardiography were done. TAFI Thr325Ile (reference sequence: rs1926447)
      polymorphism was genotyped in both studied groups using TaqMan SNP (single
      nucleotide polymorphism) genotyping assay. The genotypes of the high-risk allele
      [Thr/Ile (CT) and Ile/Ile (TT)] were significantly more frequent in patients
      compared with the control group (54.4% and 32.6% vs. 51.8% and 5.6%,
      respectively) and were also associated with an increased risk of MI [OR = 4.95,
      (95% CI: 1.80 - 13.63); P = 0.0001]. Ile325 allele carriers were more frequent in
      cases than in control subjects (60.0% vs. 31.5%) [OR = 3.26, (95% CI = 1.82 -
      5.83), P = 0.001]. The Thr325Ile SNP significantly correlated with TAFI antigen
      levels with the C/C genotype corresponding with the highest and the T/T genotype
      with the lowest TAFI antigen levels (P < 0.001). No statistically significant
      relation was found between TAFI Thr325Ile polymorphism and either the type or the
      site of MI. CONCLUSIONS: TAFI Thr325Ile and its respective plasma protein level
      could have a contribution to MI risk in the Egyptian population.This could be
      helpful in refining a risk profile for coronary heart disease (CHD) patients.

PMID- 21894806
TI  - Free breathing 2D multi-slice real-time gradient-echo cardiovascular magnetic
      resonance imaging: impact on left ventricular function measurements compared with
      standard multi-breath hold 2D steady-state free precession imaging.
AB  - OBJECTIVE: Multi-breath hold cine-imaging (standard-2D-SSFP) is the standard
      technique for ventricular function assessment. However, image acquisition is time
      consuming and breath holding is required. Ultrafast 2D real-time imaging (2D real
      time-SSFP) does not require breath holding, but spatial resolution is sacrificed.
      The accuracy of 2D real time-SSFP free-breathing ventricular function assessment
      by using an automated contour detection programme has not been systematically
      studied. METHODS AND RESULTS: Twenty-eight subjects (14 with impaired LV
      function) were investigated by 1.5 Tesla magnetic resonance imaging. Left
      ventricular short-axis images were acquired with multi-breath hold standard 2D
      SSFP and free-breathing 2D real time-SSFP. LV-volumes (EDV, ESV), EF, and mass
      were determined using a semi-automated contour detection programme. EDV, ESV, EF,
      and mass were not significantly different between real time- and standard 2D-SSFP
      in subjects (absolute differences: EDV 3.2 +/- 0.7 mL, ESV 3.0 +/- 0.3 mL, EF 1.9
      +/- 0.4%, mass 0.8 +/- 0.4 g; P > or = 0.78) and patients (absolute differences:
      EDV= 3.0 +/- 0.8 mL, ESV 3.3 +/- 1.0 mL, EF 0.9 +/- 0.5%, mass 0.9 +/- 0.5 g; P >
      or = 0.73). Automated contour detection required extensive manual correction for
      real-time imaging (< or = 86%). CONCLUSIONS: Differences in LV function
      measurements between real-time and standard 2D-SSFP are small, and not
      significant. Real-time SSFP may be used for rapid LV function assessment when
      examination time is limited.

PMID- 21894807
TI  - Prophylactic intra-aortic balloon pump reduces C-reactive protein levels and
      early mortality in high-risk patients undergoing percutaneous coronary
      intervention.
AB  - OBJECTIVE: Intra-aortic balloon pump (IABP) plays a pivotal role in the treatment
      of cardiogenic shock complicating acute myocardial infarction. However, the
      usefulness of prophylactic IABP support in high-risk patients during percutaneous
      coronary intervention (PCI) is still controversial, and its influence on the
      inflammatory response following PCI has not been well evaluated. In this study we
      sought to assess the impact of prophylactic IABP support upon C-reactive protein
      (CRP) level and clinical prognosis in high-risk patients undergoing PCI. METHODS
      AND RESULTS: A total of 106 high-risk patients diagnosed with acute ST-elevation
      or non-ST-elevation myocardial infarction (Cardiogenic shock was excluded) were
      enrolled and divided into two groups at random: 51 cases receiving PCI
      accompanied by prophylactic IABP support, and the remaining 55 cases undergoing
      PCI without IABP insertion served as the control group. CRP levels were
      determined on admission, day 3 and day 7, respectively. The troponin I (TNI)
      peak, left ventricular functions and major adverse cardiovascular events (MACE)
      were compared during follow-up. We found that the IABP group had a lower TNI peak
      as well as CRP level after PCI. Left ventricular function was improved at 2-week
      instead of 3-month followup. Although the mortality did not reach a significant
      decline after 6-month follow-up, it had improved in-hospital and at 30-day follow
      up. CONCLUSION: The use of a prophylactic IABP in high-risk patients before PCI
      could reduce the CRP level and reduce mortality during the early phase following
      PCI.

PMID- 21894808
TI  - Aortic valve calcifications on chest films: how much calcium do I need?
AB  - OBJECTIVE: Aortic valve calcifications (AVC) as seen on conventional chest films
      or on CT are associated with aortic valve stenosis (AVS). The absence of AVC on
      chest films does not exclude high grade AVS. The aim of this study was to analyse
      if there is a threshold for the detection of AVC from conventional chest films in
      patients suffering from high grade AVS. METHODS AND RESULTS: The explanted aortic
      valves of 29 patients (16 male, mean age 72.3 +/- 11.5 years) with high grade AVS
      were examined by dual-source CT. AVC were quantified using the Agatston AVC
      score. In all patients conventional chest films obtained the day before surgery
      were evaluated for the presence of AVC. Results were analysed with students t
      test, Spearman's rank correlation and ROC analysis. On conventional chest films
      AVC were visible in 18 patients. On CT all specimen presented with AVC with an
      Agatston AVC score ranging from 40.7 to 1870 (mean 991.3 +/- 463.1). In patients
      with AVC visible on chest films the AVC score was significantly higher (1264.0 +/
      318.2) when compared with patients without visible calcifications (544.9 +/-
      274.4; P < 0.0001). There was a strong correlation between the AVC score and the
      visibility of AVC on chest films (r = 0.781). ROC analysis identified an ideal
      threshold of 718 for AVC score to separate conventional chest films with and
      without visible AVC. CONCLUSION: Unlike in coronary calcifications, there is a
      threshold for identifying AVC from conventional chest films. This finding may be
      of diagnostic value, as conventional chest films may be used to
      semiquantitatively evaluate the extent of AVC.

PMID- 21894809
TI  - Association between preinfarction angina and coronary artery ectasia in the acute
      myocardial infarction.
AB  - OBJECTIVE: The objective of this study was to investigate the predictors of
      preinfarction angina (PA) and to show the association between PA and coronary
      ectasia (CE). METHODS: A total of 222 patients with acute myocardial infarction
      were included. All patients were treated with primary coronary intervention and
      interviewed by the staff physicians within 24 h of presentation after reperfusion
      had succeeded. The patients were classified according to the presence of PA and
      CE. All groups were compared statistically according to their clinicodemographic
      characteristics and angiographic results. Regression analysis was performed to
      show the predictors of PA. RESULTS: Half of the patients were defined as
      preinfarction angina (48.2%) and the success rate of primary coronary
      intervention did not differ statistically in the PA present group. More than half
      of the patients had multivessel disease and coronary ectasia was found in the
      11.7%. The right coronary artery (RCA) was the most common localization for
      ectasia and 61.5% of the ectatic vessels were also infarct-related. Diabetes
      mellitus, hypertension and previous coronary heart disease were slightly more
      common in the PA present group. In the regression analysis, coronary ectasia,
      multivessel disease and previously diagnosed coronary artery disease were
      independent predictors of PA (P = 0.001, P = 0.01 and P = 0.03, respectively)
      CONCLUSIONS: CE is more common in patients with PA and more than half of the
      patients showed CE in the infarct-related vessel. CE and multivessel disease are
      independent predictors of PA. The success rate of primary coronary intervention
      in ectatic infarct-related vessels did not differ in the PA group.

PMID- 21894810
TI  - Exercise intolerance due to sustained atrial bigeminy with short coupling
      interval.
AB  - Atrial bigeminy is a supraventricular arrhythmia rarely associated with severe
      symptoms. We report the case of a 22-year-old woman with no prior cardiac disease
      presenting with exercise intolerance since several months. No apparent heart
      disease other than a spontaneous conducted atrial bigeminy with a short coupling
      interval was found. At bicycle ergometric testing, symptoms occurred, because of
      an inadequate increase in pulse rate, due to sustained atrial bigeminy. At
      electrophysiological study, an ectopic atrial focus at the right atrial septum
      was successfully ablated.

PMID- 21894811
TI  - The vulnerability of fractional flow reserve.

PMID- 21894812
TI  - A patient treated with tilt training and midodrine after 68 seconds asystole
      during head-up tilt table testing.
AB  - Neurocardiogenic syncope is a relatively common cause of syncope and is diagnosed
      by head-up tilt testing. A 21-year-old man was examined for frequent syncope
      episodes which occurred after episodes of blood drawing and standing in queue.
      Syncope developed in tilt table testing. After about 68 seconds, sinus rhythm
      returned. Recent reports have shown that tilt training is a very effective
      therapy for recurrent neurocardiogenic syncope. In our case, the patient was
      treated with midodrine 2.5 mg once a day and a tilt training programme. Therapy
      resulted in improvement and during a follow-up of six months, no major events
      occurred.

PMID- 21894813
TI  - Optimization of biventricular pacing via strain dyssynchrony measurements in a
      paediatric patient.
AB  - Cardiac resynchronization therapy is increasingly being used in the paediatric
      population as a tool for managing patients with heart failure. Various non
      invasive parameters have been used to optimize the settings on the biventricular
      pacemaker. We describe implantation of a biventricular pacemaker in a nineteen
      month-old child because of intractable heart failure. By analysing a 17-segment
      model using strain analysis of the left ventricle, we were able to place the left
      ventricular lead at the latest activated segment. Furthermore, we were able to
      minimize the dyssynchrony of the left ventricle when evaluating a range of
      pacemaker settings.

PMID- 21894814
TI  - You can't judge a book by its cover: a pseudo 1st degree A-V block in apparent
      absence of retrograde conduction.
AB  - We report 3 tracings from an electrophysiological study in which the appearance
      of a pseudo 1st degree A-V block helped to unmask the presence of a retrograde
      conduction, previously unrecognized. Our case highlights the importance in
      specific cases to have more than 2 intracardiac tracings during an
      electrophysiological study.

PMID- 21894815
TI  - Myocardial hypoperfusion detected by cardiac computed tomography in an adult
      patient with heart failure after classic repair for corrected transposition of
      the great arteries.
AB  - A 69-year-old male with a history of classic repair for corrected transposition
      of the great arteries (TGA) arrived at our hospital with dyspnoea upon exertion.
      Echocardiography revealed severe dilation and diffuse hypokinesis of the systemic
      ventricle without obvious valvular dysfunction. Cardiac computed tomography (CT)
      revealed no significant stenosis. However, the morphological right coronary
      artery (CA) on the left side was unequally distributed to the large systemic
      ventricle and was mostly obscured, especially on the anterior wall. A low
      attenuation area in the anterior wall of the systemic ventricle and prominent
      trabeculations suggested ischaemia or infarction. We considered that chronic
      myocardial hypoperfusion due to an inadequate coronary arterial supply was one
      cause of the exacerbated heart failure long after the classic repair. Cardiac CT
      is useful for evaluating the distribution of the CA and to predict blood supply
      to the myocardium in corrected TGA.

PMID- 21894816
TI  - Successful management of Listeria monocytogenes pericarditis: case report and
      review of the literature.
AB  - Listeria monocytogenes, although an uncommon cause of illness in the general
      population, is feared principally because of the morbidity and mortality
      associated with CNS infections. Cardiovascular involvement with L. monocytogenes
      is very rare, and has been limited to endocarditis. We describe a case of
      Listeria pericarditis, which occurred in a 60-year-old man with Child-Pugh B
      cirrhosis who presented to the emergency department with asthenia, anorexia, and
      respiratory distress. The echocardiogram showed severe pericardial effusion and
      after pericardiocentesis, L. monocytogenes was isolated in the culture of
      pericardial fluid. After surgical pericardiectomy with draining of the
      pericardial effusion and antibiotic treatment with ampicillin, the patient
      experienced a slow, but full recovery. Documentation of L. monocytogenes
      pericarditis is an extremely rare entity with very scarce reports in medical
      literature, and is usually associated with a very poor prognosis. A case report
      is presented together with a review of the literature.

PMID- 21894817
TI  - Intimal sarcoma of the pulmonary artery--diagnostic challenge.
AB  - Pulmonary artery intimal sarcoma is a rare tumour and the diagnosis is often
      delayed. We report the case of a woman with a primary pulmonary artery intimal
      sarcoma who presented with massive pulmonary embolism. The definitive diagnosis
      was elucidated after the patient's death by autopsy specimen. We discuss the
      diagnosis and lessons learned from this case.

PMID- 21894818
TI  - Ebstein's anomaly with refractory atrial tachycardia.
AB  - The incidence of accessory pathways in patients with Ebstein's anomaly is high,
      ranging from 20% to 30%, with right and multiple pathways being more commonly
      encountered. Radiofrequency ablation can eliminate the accessory pathway, but
      success rates of ablation treatment and the chances of recurrence are generally
      less satisfactory as compared to those observed when the procedure is performed
      on structurally normal hearts. We report the case of a 56-year-old man with
      Ebstein's anomaly and refractory atrial tachycardia. The special abnormality of
      the tricuspid valve led to the failure of preoperative electrophysiological
      mapping and radiofrequency ablation treatment. Finally, the anomalies observed in
      this patient were corrected with simultaneous surgery and pathway resection.

PMID- 21894819
TI  - A giant post-dissection aneurysm of the ascending aorta in an octogenarian.
AB  - Aneurysm formation is a well-known complication of untreated long-standing
      dissection of the aorta. Despite numerous advances in cardiac surgery, intrinsic
      diseases of the ascending aorta and aortic arch requiring surgical therapy,
      remain a technical challenge. However, surgery is the only option for effective
      treatment of ascending aorta aneurysm but carries an increased risk of severe
      morbidity and mortality, particularly in the elderly. We report on the successful
      repair of a giant ascending aorta aneurysm due to chronic dissection in an
      elderly woman with dyspnoea as main symptom.

PMID- 21894820
TI  - True left ventricular aneurysm after blunt chest trauma.
AB  - Left ventricular aneurysms are common in clinical practice. Although their
      underlying aetiology is generally clear by the clinical context, it can be hard
      to define the exact cause in some cases. We report a case of a patient in whom
      cardiac MRI provided important information about the differential diagnosis of a
      left ventricular aneurysm.

PMID- 21894821
TI  - Meningo-encephalitis as initial manifestation of a fatal atrio-oesophageal
      fistula after atrial fibrillation ablation.
AB  - OBJECTIVE: Meningo-encephalitis as a complication of an atrio-oesophageal fistula
      (AEF) after left atrial radiofrequency ablation (RFA) has been only rarely
      reported. CASE REPORT: A 49-year-old man with persisting atrial fibrillation and
      oral anticoagulation underwent RFA without initial complication. Four weeks after
      the procedure, however, fever, emesis, and confusion occurred. Clinical
      neurologic examination revealed somnolence, partial disorientation, psychomotor
      agitation, and athetotic movements of the upper limbs. CSF-investigations
      revealed 100/3 granulocytes and MR meningeal enhancement and multiple parenchymal
      enhancing spots. After haematemesis, seizure, and resuscitation, an AEF was
      detected by the third gastroscopy and confirmed by thoracic CT. Because of the
      septic state surgeons refused to close the fistula. The patient died 10 days
      after the clinical onset of meningo-encephalitis from cerebral oedema despite
      adequate antibiotic treatment. CONCLUSIONS: An AEF after RFA may initially
      manifest as septic meningo-encephalitis, even after a four-week symptom-free
      interval. Manipulations within the oesophagus after diagnosis of an AEF are
      contraindicated. The procedure of choice to diagnose an AEF is thoracic CT with
      contrast medium. Surgical closure of the fistula should be tried immediately
      after diagnosis despite sepsis.

PMID- 21894822
TI  - Kounis syndrome: myocardial infarction secondary to an allergic insult--a rare
      clinical entity.
AB  - The association of an acute coronary syndrome with mast cell activation secondary
      to allergen exposure is known as the Kounis syndrome. We present two cases of the
      Kounis syndrome: (i) one was misdiagnosed as acute ST elevation myocardial
      infarction and treated with thrombolytics; (ii) the second diagnosis was made
      after a recurrence two months after the first incident.

PMID- 21894823
TI  - Dentistry meets Madison Avenue.

PMID- 21894824
TI  - Government super heroes on mission to rout out fraud.

PMID- 21894825
TI  - Chad P. Gehani, NYSDA president 2011-2012. A singular voice for all dentists.

PMID- 21894828
TI  - Conversion prosthesis: fabricating chairside immediate complete denture.
AB  - Patients presenting with mutilated dentition requiring multiple extractions can
      be treated effectively with conventional techniques for fabricating an immediate,
      complete, removable dental prosthesis (commonly known as an immediate complete
      denture). When a patient presents with a full-arch fixed partial denture with few
      and severely compromised abutments, it often precludes the possibility of staging
      the extractions prior to the fabrication of an immediate complete denture. A
      technique for fabrication of a functional, chairside, immediate complete denture
      is presented.

PMID- 21894827
TI  - Gagging.
AB  - Gagging is a protective reflex to stop unwanted entry into the mouth and
      oropharynx. Some people have a reduced or absent reflex, while others have a
      pronounced one. Pronounced gag reflexes can compromise all aspects of dentistry,
      from the diagnostic procedures of examination and radiography to any form of
      active treatment. In some patients with marked gagging reflexes, it can lead to
      avoidance of treatment. Many techniques have been described that attempt to
      overcome this problem, and a variety of management strategies is necessary to aid
      the delivery of dental care. This is a review of the etiology of gagging
      problems, clinical assessment, and their classification and categorization prior
      to clinical treatment. It discusses as well methods for managing patients with
      gag reflexes during dental treatment.

PMID- 21894829
TI  - IMRA: Immediate maxillary replacement appliance for anterior teeth.
AB  - When faced with the need for emergency replacement of anterior teeth, the problem
      for dentists and their patients is how can lost teeth be replaced quickly?
      Laboratory-fabricated replacement appliances require significant time and
      expense, not to mention an extended period, during which the patient remains
      edentulous. This report describes a procedure to construct an immediate, low-cost
      replacement for one or more missing anterior teeth-one that requires no
      laboratory time. The resulting appliance is meant only as a stop gap and does not
      support chewing; but it does offer an esthetically pleasing, removable prosthesis
      that provides phonetic and lip support during the short time necessary to
      fabricate and place a permanent prosthesis.

PMID- 21894830
TI  - Recurrent peripheral odontogenic fibroma. Case report.
AB  - Peripheral odontogenic fibroma (POF), an extraosseous variant of the central
      odontogenic fibroma, is considered an uncommon benign gingival lesion with a
      small recurrence rate. Clinically, it mimics a variety of benign neoplasms,
      metastases and reactive lesions, but it is most commonly confused with the
      peripheral ossifying fibroma. In this report, we describe a healthy 32-year-old
      male who was seen with a recurrent POF of the right maxilla. The surgical
      excision site was repaired using a free palatal graft, leading to a favorable
      outcome in an esthetic region of the oral cavity.

PMID- 21894831
TI  - Caries management with fluoride varnish of children in U.S.
AB  - Fluoride varnish prolongs the contact time between fluoride and tooth surface to
      reduce caries. Its active ingredient is usually 5% sodium fluoride, or 22,600 ppm
      fluoride. Its use as an "off-label" approved drug for caries control in the
      United States has been on the rise, along with increasing evidence of its
      efficacy in case-based studies. It sets rapidly on teeth, and it is simple, quick
      and easy to apply. Side effects or complications of its use are rare. Gagging and
      swallowing are unusual. The risk of dental fluorosis is minimal. And it can be
      safely used in young children.

PMID- 21894832
TI  - Caries experience among Chinese-American children in Manhattan Chinatown.
AB  - There is little research on the oral health status of Chinese-American (CA)
      children in the U.S. and Asian/Pacific Islanders in general. The purpose of this
      study was to characterize the dental caries experience of a CA child population
      in Manhattan Chinatown, New York City. A five-year chart review of 545 initial
      dental exams of patients aged 2 to 11 was conducted at a community clinic serving
      an immigrant CA population. DMFT/dft were compared to National Health and
      Nutrition Examination Survey (NHANES) and analyzed for associations among
      birthplace, language and untreated tooth decay at recall. Subject mean dft was
      higher compared to NHANES data both in aggregate and ethnic/race subgroups.
      Subjects had lower DMFT ccmpared to the national data. Significant difference was
      found between U.S. and non-U.S.-born mean dft. Asian Pacific Islander Americans
      include a fast-growing immigrant pediatric population at high risk for tooth
      decay.

PMID- 21894834
TI  - Congress passes legislation exempting dentists from FTC's Red Flags Rule.

PMID- 21894833
TI  - Comparison of efficacy of sodium hypochlorite with sodium perborate in removal of
      stains from heat-cured clear acrylic resin.
AB  - Acrylic resin bases of removable dentures attract stains and odor-producing
      organic and inorganic deposits. The use of chemical denture cleanser soaks is the
      most popular method of denture cleansing. This study was undertaken to compare
      the efficacy of two different denture cleansers--sodium perborate (Clinsodent)
      and sodium hypochlorite (VI-Clean)--in removing tea, coffee, turmeric and tobacco
      (paan) stains from heat-cured clear acrylic resins. Distilled water was used as a
      control. Both Clinsodent and VI-Clean were found to be the least effective in
      removing coffee stains and best for removing turmeric stain. It is necessary that
      the dental professional be aware of these results to ensure that denture wearers
      know how to select the appropriate denture cleanser.

PMID- 21894835
TI  - Keeping your millions.

PMID- 21894836
TI  - Interview with Dr. Eric Geist on his campaign for vice president of the American
      Association of Oral and Maxillofacial Surgeons (AAOMS).

PMID- 21894837
TI  - Green fundraising.

PMID- 21894838
TI  - Kidney failure in Canada.

PMID- 21894839
TI  - Development of the Self-Care for Adults on Dialysis tool (SCAD).
AB  - The objective of this study was to develop a norm-referenced tool that would
      measure the self-care abilities and behaviours for adults requiring dialysis
      therapy. Guided by the Self-Care Deficit Nursing Theory (Orem, 2001) and an
      extensive review of the research literature, the Lay Care Giving for Adults on
      Dialysis tool (LC-GAD) (Horsburgh, Laing, Beanlands, Meng, & Harwood, 2008) was
      modified to develop the Self-Care for Adults on Dialysis (SCAD) measure. Content
      validity testing of the SCAD was conducted by a panel of 13 nephrology nursing
      experts. The tool was modified based on study findings. Further psychometric
      testing is required. When completed the SCAD tool will guide nurses to design and
      evaluate supportive self-care interventions for adults requiring dialysis.

PMID- 21894840
TI  - Thinking outside the box: an extraordinary woman on home peritoneal dialysis.
AB  - At the home peritoneal dialysis unit (HPDU) of the University Health Network in
      Toronto, Ontario, we offer training to help patients perform peritoneal dialysis
      at home with ongoing support, which includes clinic visits and on-call services.
      Not every patient is able to carry out independent dialysis, however. Additional
      support at home is often provided in conjunction with Community Care Access and
      home care nurses. We recently had the privilege to learn from an extraordinary
      patient, whose special needs provided us with challenges and opportunities. This
      paper describes the interaction, flexibility and creativity between our unit,
      home care nurses, the patient and her family. It demonstrates that with
      commitment, there truly are many ways to solve even seemingly impossible
      problems.

PMID- 21894841
TI  - Medication adherence in patients with chronic kidney disease.

PMID- 21894842
TI  - Steps to safe swimming for patients on peritoneal dialysis.

PMID- 21894844
TI  - The myth of privacy.

PMID- 21894843
TI  - Getting older.

PMID- 21894845
TI  - Introduction: A view of Rhode Island pediatrics.

PMID- 21894846
TI  - Developmental screening in a pediatric care practice.

PMID- 21894847
TI  - Early identification of eating disorders in primary care pediatrics.

PMID- 21894848
TI  - Fostering health: Health care for children and youth in foster care.

PMID- 21894849
TI  - Overuse injuries in the young athlete.

PMID- 21894850
TI  - Meaningful use for the pediatrician.

PMID- 21894851
TI  - The evolution of quality improvement.

PMID- 21894852
TI  - Medical radiation: fret or forget?

PMID- 21894853
TI  - Rhode Island physicians' health information technology (HIT) use, 2009-2011.

PMID- 21894855
TI  - Medical terms, up to the letter 'Z'.

PMID- 21894854
TI  - Splenic cyst manifesting as gastric outlet obstruction.

PMID- 21894856
TI  - [The hospital staff exposed to deleterious substances].

PMID- 21894857
TI  - [Cerebrovascular accidents. A permanent and temporal fight].

PMID- 21894858
TI  - [The advances' effects in stroke treatment].
AB  - Thanks to epidemiology, the weight of severe complications from strokes in terms
      of the rate of incidence and mortality is better known. Risk and prognostic
      factors can be organised into a hierarchy, treatments and primary and
      preventative care can be assessed.

PMID- 21894859
TI  - [Physiopathology of strokes].
AB  - Strokes form a very heterogeneous pathology with numerous and varied causes. They
      present a different physiopathology depending on the ischemic or haemorrhagic
      character of the stroke.

PMID- 21894860
TI  - [Aetiology and treatment of strokes].
AB  - Aetiological explorations of ischemic strokes must be classified hierarchically
      with a first-line assessment to be carried out in the first few hours. This
      assessment will detect the main causes and direct the treatment. If necessary, a
      more specialised assessment will be carried out afterwards.

PMID- 21894861
TI  - [Stroke as a therapeutic emergency].
AB  - A stroke is an emergency which can be treated as soon as it occurs thanks to
      thrombolysis. Prognosis is linked to the quality of the technical and relational
      care ministered by an expert team, aware of the complications and attentive to
      the needs of the patient.

PMID- 21894862
TI  - [The neurovascular unit to reduce management delays].

PMID- 21894864
TI  - [Nursing care in a rehabilitation department].
AB  - The nurse enables the patient with sequelae resulting from a stroke to return
      home thanks to individualised care. She takes part in the patient's
      rehabilitative project which aims to restore independence and thereby favour his
      or her integration. The involvement of the family in the care project helps in
      the construction of a life project.

PMID- 21894863
TI  - [The role of nurses in a care, training and research network].
AB  - A care network devoted to strokes within a region can be effective on condition
      that the separations between medical practices are removed and a measurement tool
      is made available. It enables the immediate mortality and the rate of recurrence
      to be reduced. It also helps to prolong life expectancy without a stroke.

PMID- 21894866
TI  - [To recover after cerebrovascular accident].

PMID- 21894865
TI  - [Multi-disciplinary rehabilitative care after a stroke].
AB  - The care given to patients having suffered a stroke requires the intervention of
      several specialised therapists. Generalising what is acquired through
      rehabilitation in daily life remains the common objective of the therapists as
      well as the nursing teams.

PMID- 21894868
TI  - [The genogram to favour interdisciplinarity in rehabilitation].

PMID- 21894867
TI  - [The social and professional integration of the patient].
AB  - The rehabilitation and social and professional integration department of the
      Mutual Centre for Re-education and Functional Rehabilitation in Kerpape,
      Brittany, is part of an early integration approach. It assesses situations of
      disability and a person's individual and social circumstances, notably after a
      stroke. A multi-disciplinary team supports patients for one year after they leave
      the centre, with the aim of supporting their social and professional
      reintegration.

PMID- 21894869
TI  - [6/10 Creating trust relations with patients and their relatives].

PMID- 21894870
TI  - Evaluating your participation with insurance plans.

PMID- 21894871
TI  - The amalgam controversy: where do we go from here?

PMID- 21894872
TI  - The rise in prescription drug abuse: raising awareness in the dental community.
AB  - Prescription drugs classified as controlled dangerous substances are essential
      therapeutic modalities in treating a variety of healthcare conditions; however,
      their pleasurable side effects can appeal to patients for uses other than their
      intent. As a result, unfortunate consequences of prescription drug use can arise.
      Misuse or abuse of prescription drugs can contribute to addictive behaviors,
      serious health risks, and potentially, death. It is imperative that the dental
      community remains educated and informed of nationwide healthcare trends, and
      prescription drug abuse is no exception. Ethically, dentists should be able to
      respond in a manner that addresses the best interests of their patients. To
      respond appropriately, dentists need to understand the terminology of
      prescription drug abuse; be able to identify and describe the drugs most often
      misused or abused; be able to identify individuals who may be at risk for
      prescription drug abuse; and be prepared to manage patients at risk in the dental
      setting.

PMID- 21894873
TI  - The role of remineralizing agents in dentistry: a review.
AB  - Minimal intervention is a key phrase in today's dental practice. Minimal
      intervention dentistry (MID) focuses on the least invasive treatment options
      possible in order to minimize tissue loss and patient discomfort. Concentrating
      mainly on prevention and early intervention of caries, MID's first basic
      principle is the remineralization of early carious lesions, advocating a
      biological or therapeutic approach rather than the traditional surgical approach
      for early surface lesions. One of the key elements of a biological approach is
      the usage and application of remineralizing agents to tooth structure (enamel and
      dentin lesions). These agents are part of a new era of dentistry aimed at
      controlling the demineralization/ remineralization cycle, depending upon the
      microenvironment around the tooth. This article details the various agents that
      enhance and/or promote remineralization and discusses their clinical
      implications.

PMID- 21894874
TI  - "Digidontics": the computerization of restorative dentistry--a case report.
AB  - Today's practitioners of dentistry can be overwhelmed by the need to analyze,
      understand, prioritize, and implement the extraordinary amounts of knowledge and
      technical skill required to practice ideal dentistry. Continuing education is not
      just necessary; an increasingly informed patient population demands it. Among
      many technological advancements, computers have permeated the mainstream of
      restorative dentistry. The conventional systems of radiography and impressioning
      are the latest to face a digital counterpart. This case presentation demonstrates
      how cone beam computerized tomography (CBCT) and a dedicated digital
      impressioning system can be used alongside conventional techniques to obtain
      excellent esthetic and functional results.

PMID- 21894875
TI  - Orthodontic extrusion and implant restoration to manage localized advanced bone
      loss: a clinical case review.
AB  - Restorative dentists must consider and respect the preferences of their patients
      when developing treatment plans. They must also communicate openly with both the
      patient and their interdisciplinary team regarding treatment objectives,
      particularly in challenging cases such as the one presented herein, in which the
      patient had severe recession above her upper laterals and cuspids, was
      congenitally missing molars, and had a history of full-mouth scaling and root
      planing as well as periodontal surgery in the maxillary arch. This case
      incorporated four phases of treatment--endodontics, orthodontics, surgical, and
      restorative--to achieve the desired results.

PMID- 21894876
TI  - Clinical performance of scientifically designed, hot isostatic-pressed (HIP'd)
      zirconia cores in a bilayered all-ceramic system.
AB  - PURPOSE: The success of bilayered all-ceramic restorations is dependent upon the
      combination and contributions of the three principal components of these
      restorations: core material, core design, and core-veneer interface. The purpose
      of this paper is to describe the fabrication and clinical survival of optimized
      ceramic restorations having an explicit, scientifically designed core, machined
      from HIP'd isotropic zirconia and veneered using a specific protocol with
      thermally compatible porcelain. MATERIALS AND METHODS: Using a consistent
      clinical and laboratory protocol in a multicenter setting, 3,192 bilayered single
      and 797 bilayered splinted units were fabricated and placed on teeth and implant
      abutments in 1,007 patients. Approximately 61.7% (n = 2,462) were posterior
      restorations and 38.3% (n = 1,527) were anterior. Of the total, approximately
      5.7% (n = 227) were placed on implant abutments. Survival of the restorations was
      determined with the Kaplan-Meier (KM) method by tooth number. RESULTS: For the
      3,989 units placed, 9 failures were recorded. The KM survival of most zirconia
      restorations, when segregated by tooth number, was 100%. Exceptions were the 9
      failed units, with a KM survival between 88% and 99% for those restorations. Six
      restorations failed within the first year of service, including three failed
      cores. Examination of those restorations revealed failure was related to initial
      design, quality assessment, or fabrication inconsistencies. CONCLUSION: The
      incorporation of a reinforcing ring beam onto an anatomically shaped core made
      from end-state HIP'd zirconia, in partnership with a thermally compatible
      veneering porcelain and a specific application protocol, resulted in extremely
      high survival rates for both anterior and posterior all-ceramic restorations
      after medium-term clinical use. These results equal or surpass the equivalent
      term success rates of porcelain-fused-to-metal restorations.

PMID- 21894877
TI  - Curing lights.

PMID- 21894878
TI  - Restoring esthetics and function in an edentulous patient with ectodermal
      dysplasia.

PMID- 21894879
TI  - A disconnect of epic proportions.

PMID- 21894880
TI  - Intermolecular interaction energies in molecular crystals: comparison and
      agreement of localized Moller-Plesset 2, dispersion-corrected density functional,
      and classical empirical two-body calculations.
AB  - A comparative analysis of the intermolecular energy for a data set including 60
      molecular crystals with a large variety of functional groups has been carried out
      using three different computational approaches: (i) a method based on a
      physically meaningful empirical partition of the interaction energy (PIXEL), (ii)
      density functional methods with a posteriori empirical correction for the
      dispersion interactions (DFT-D), and (iii) a full periodic ab initio quantum
      mechanical method based on Moller-Plesset perturbation theory for the electron
      correlation using localized crystal orbitals (LMP2). Due to the large
      computational cost, LMP2 calculations have been restricted to a subset of seven
      molecular crystal comprising benzene, formic acid, formamide, succinic anhydride,
      urea, oxalic acid, and nitroguanidine, and the results compared with PIXEL and
      DFT-D data as well as with the experimental data show excellent agreement among
      all adopted methods. This shows that both DFT-D and PIXEL approaches are robust
      predictive tools for studying molecular crystals. A detailed analysis shows a
      very similar dispersion contribution of the two methods across the 60 considered
      molecular crystals. The study also confirms that pure DFT shows serious
      deficiencies in properly handling molecular crystals in which the dispersive
      contribution is large. Due to the negligible requested computational resources,
      PIXEL is the method of choice in screening of a large number of molecular
      crystals, an essential step to predict crystal polymorphism or to study crystal
      growth processes. DFT-D can then be used to refine the ranking emerged from PIXEL
      calculations due to its general applicability and robustness in properly handling
      short-range interactions.

PMID- 21894881
TI  - Silanediols: a new class of hydrogen bond donor catalysts.
AB  - Silanediols are introduced as a new class of hydrogen bond donor catalysts for
      the activation of nitroalkenes toward nucleophilic attack. Excellent yields of
      product are obtained for the conjugate addition of indole to beta-nitrostyrene
      catalyzed with a stable, storable dinaphthyl-derived silanediol. The preparation
      and structural characterization of a C(2)-symmetric chiral silanediol is also
      reported along with its ability to catalyze the conjugate addition reaction.

PMID- 21894883
TI  - Copper-catalyzed Perkin-acyl-Mannich reaction of acetic anhydride with pyridine:
      expeditious entry to unconventional piperidines.
AB  - A regioselective introduction of a methoxycarbonyl methyl group at the C(2)
      position of unsubstituted pyridine has been accomplished with catalytic amounts
      of copper(II) triflate in mild reaction conditions. The N-acetyl-1,2
      dihydropyridyl acetic acid methyl ester obtained is a valuable building block for
      the synthesis of new polyfunctionalized piperidine derivatives bearing
      unconventional substitution patterns.

PMID- 21894884
TI  - Palladium-catalyzed regio- and enantioselective fluorination of acyclic allylic
      halides.
AB  - This report describes the Pd(0)-catalyzed fluorination of linear allylic
      chlorides and bromides, yielding branched allylic fluorides in high selectivity.
      Many of the significant synthetic limitations previously associated with the
      preparation of these products are overcome by this catalytic method. We also
      demonstrate that a chiral bisphosphine-ligated palladium catalyst enables highly
      enantioselective access to a class of branched allylic fluorides that can be
      readily diversified to valuable fluorinated products.

PMID- 21894885
TI  - Vaporization and formation enthalpies of 1-alkyl-3-methylimidazolium
      tricyanomethanides.
AB  - Thermochemical studies of the ionic liquids 1-ethyl-3-methylimidazolium
      tricyanomethanide [C(2)MIM][C(CN)(3)] and 1-butyl-3-methylimidazolium
      tricyanomethanide [C(4)MIM][C(CN)(3)] have been performed in this work.
      Vaporization enthalpies have been obtained using a recently developed quartz
      crystal microbalance (QCM) technique. The molar enthalpies of formation of these
      ionic liquids in the liquid state were measured by means of combustion
      calorimetry. A combination of the results obtained from QCM and combustion
      calorimetry lead to values of gaseous molar enthalpies of formation of
      [C(n)MIM][C(CN)(3)]. First-principles calculations of the enthalpies of formation
      in the gaseous phase for the ionic liquids [C(n)MIM][C(CN)(3)] have been
      performed using the CBS-QB3 and G3MP2 theory and have been compared with the
      experimental data. Furthermore, experimental results of enthalpies of formation
      of imidazolium-based ionic liquids with the cation [C(n)MIM] (where n = 2 and 4)
      and anions [N(CN)(2)], [NO(3)], and [C(CN)(3)] available in the literature have
      been collected and checked for consistency using a group additivity procedure. It
      has been found that the enthalpies of formation of these ionic liquids roughly
      obey group additivity rules.

PMID- 21894886
TI  - Efficient and scalable one-pot synthesis of 2,4-dienols from cycloalkenones:
      optimized total synthesis of valerenic acid.
AB  - A mild and selective one-pot procedure to provide 2,4-dienols from simple
      cycloalkenones in high yields is described. This transformation is based on the
      in situ formation of acid-labile allylic alcohols, which on treatment with
      trifluoroacetic acid undergo a formal [1,3]-hydroxy migration to form diastereo-
      and enantiomerically enriched 2,4-dienols. The usefulness of this protocol is
      demonstrated in a short synthesis of valerenic acid.

PMID- 21894887
TI  - Comparison of DNA extraction methods and development of duplex PCR and real-time
      PCR to detect tomato, carrot, and celery in food.
AB  - Traceability is of particular importance for those persons who suffer allergy or
      intolerance to some food component(s) and need a strict avoidance of the
      allergenic food. In this paper, methodologies are described to fingerprint the
      presence of allergenic species such as carrot, tomato, and celery by DNA
      detection. Three DNA extraction methods were applied on vegetables and foods
      containing or not containing the allergens, and the results were compared and
      discussed. Fast SYBR Green DNA melting curve temperature analyses and duplex PCR
      assays with internal control have been developed for detection of these
      allergenic vegetables and have been tested on commercial foods. Spiking food
      experiments were also performed, assessing that limits of detection (LOD) of 1
      mg/kg for carrot and tomato DNA and 10 mg/kg for celery DNA have been reached.

PMID- 21894888
TI  - Synthesis of oxosumanenes through benzylic oxidation.
AB  - Oxosumanenes were synthesized through benzylic oxidation. The electronic and
      redox properties were revealed to exhibit the expanded pi-conjugation compared to
      sumanene. Single-crystal X-ray analysis of monooxosumanene showed columnar pi
      stacking in a concave-convex fashion. Stereoselective trimethylation of the
      trioxo derivative was performed via 1,2-addition to the carbonyl groups.

PMID- 21894889
TI  - Processable cyclic peptide nanotubes with tunable interiors.
AB  - A facile route to generate cyclic peptide nanotubes with tunable interiors is
      presented. By incorporating 3-amino-2-methylbenzoic acid in the D,L-alternating
      primary sequence of a cyclic peptide, a functional group can be presented in the
      interior of the nanotubes without compromising the formation of high aspect ratio
      nanotubes. The new design of such a cyclic peptide also enables one to modulate
      the nanotube growth process to be compatible with the polymer processing window
      without compromising the formation of high aspect ratio nanotubes, thus opening a
      viable approach toward molecularly defined porous membranes.

PMID- 21894890
TI  - Rotational diffusion analysis of polyethylene glycol induced protein
      interactions.
AB  - Protein intermolecular depletion interactions induced by polyethylene glycol
      (PEG) depend largely on its concentration and molecular weight. Herein, we
      investigated the effects of various concentrations and molecular weights of PEG
      on lysozyme interactions through the analysis of protein rotational diffusion,
      which is susceptible to intermolecular interactions at short range. To this end,
      we measured fluorescence anisotropy of fluorescein-tagged lysozyme added as a
      tracer in concentrated native lysozyme solutions and introduced a protein
      concentration-dependent interaction parameter, k(rot). The results show the
      nonmonotonic changes in k(rot) as the concentrations of PEG10000 and 6000 are
      increased. The depletion attractions are characterized by the decrease in k(rot),
      indicating an increase of a degree at which protein rotational diffusion slows
      down. The influences of temperature on the lysozyme rotational diffusion and
      k(rot) were also measured, and the validity of this approach was checked through
      comparison with the colloidal theory.

PMID- 21894891
TI  - Ground- and excited-state properties of Zn(II) tetrakis(4-tetramethylpyridyl)
      pophyrin specifically encapsulated within a Zn(II) HKUST metal-organic framework.
AB  - We have examined the photophysical properties of Zn(II) tetramethylpyridyl
      porphyrin (ZnT4MPyP) specifically encapsulated within the cubioctahedral cavities
      of a ZnHKUST metal- organic framework. The encapsulated ZnT4MPyP exhibits a Soret
      maxima at ~458 nm that is bathochromically shifted relative to ZnT4PyP in ethanol
      solution (Soret maxima centered at 440 nm). The corresponding emission spectra of
      the encapsulated porphyrin exhibit resolvable bands centered at 636 and 677 nm
      relative to a single broad emission band of the ZnT4MPyP in ethanol solution
      centered at 636 nm with a shoulder situated near ~660 nm. The fluorescence
      lifetime of the encapsulated porphyrin is also perturbed relative to that of the
      free porphyrin in solution (1.88 ns for the encapsulated porphyrin relative to
      1.2 ns in solution). These results are consistent with the ZnT4MPyP being in a
      more constrained environment in which the peripheral pyridyl groups have
      restricted rotational motion. The ZnT4MPyP triplet lifetime is also affected by
      encapsulation, giving rise to a longer lifetime (tau ~ 3.3 ms) relative to that
      for the free porphyrin in solution (tau ~ 1 ms). The triplet-state results
      indicate that nonplanar vibrational modes of the porphyrin leading to intersystem
      crossing are retained by encapsulation of the porphyrin but that either the
      density of vibrational states or the specific nonplanar modes coupling the
      singlet and triplet states may be perturbed, resulting in the longer observed
      lifetime.

PMID- 21894892
TI  - Laser ablation ICP-MS Co-localization of mercury and immune response in fish.
AB  - Mercury (Hg) contamination is a global issue with implications for both ecosystem
      and human health. In this study, we use a new approach to link Hg exposure to
      health effects in spotted gar (Lepisosteus oculatus) from Caddo Lake (TX/LA).
      Previous field studies have reported elevated incidences of macrophage centers in
      liver, kidney, and spleen of fish with high concentrations of Hg. Macrophage
      centers are aggregates of specialized white blood cells that form as an immune
      response to tissue damage, and are considered a general biomarker of contaminant
      toxicity. We found elevated incidences of macrophage centers in liver of spotted
      gar and used a new technology for ecotoxicology studies, laser ablation
      inductively coupled plasma-mass spectrometry (LA-ICP-MS), to colocalize
      aggregates and Hg deposits within the tissue architecture. We conclude that Hg
      compromises the health of spotted gar in our study and, perhaps, other fish
      exposed to elevated concentrations of Hg.

PMID- 21894893
TI  - Molecular model with quantum mechanical bonding information.
AB  - The molecular structure can be defined quantum mechanically thanks to the theory
      of atoms in molecules. Here, we report a new molecular model that reflects
      quantum mechanical properties of the chemical bonds. This graphical
      representation of molecules is based on the topology of the electron density at
      the critical points. The eigenvalues of the Hessian are used for depicting the
      critical points three-dimensionally. The bond path linking two atoms has a
      thickness that is proportional to the electron density at the bond critical
      point. The nuclei are represented according to the experimentally determined
      atomic radii. The resulting molecular structures are similar to the traditional
      ball and stick ones, with the difference that in this model each object included
      in the plot provides topological information about the atoms and bonding
      interactions. As a result, the character and intensity of any given interatomic
      interaction can be identified by visual inspection, including the noncovalent
      ones. Because similar bonding interactions have similar plots, this tool permits
      the visualization of chemical bond transferability, revealing the presence of
      functional groups in large molecules.

PMID- 21894894
TI  - Macroscopic liquid crystal response to isolated DNA helices.
AB  - Nematic liquid crystals (LC) were exposed to isolated DNA molecules extended on a
      surface that imparted a negligible influence on the LC orientation. Although
      single-stranded DNA aligned the LC in the extension direction, double-stranded
      DNA (dsDNA) caused alignment at an oblique angle, providing a characteristic
      response to the chiral dsDNA helix that was readily observed optically. The
      intrinsic amplification due to LC orientational correlations enabled a
      macroscopic visible response to a single molecule of extended dsDNA.

PMID- 21894895
TI  - A new high-performance liquid chromatography-tandem mass spectrometry method
      based on dispersive solid phase extraction for the determination of the mycotoxin
      fusarin C in corn ears and processed corn samples.
AB  - Fusarin C is a mycotoxin that is produced by a variety of Fusarium species and is
      therefore a possible contaminant in food and feed. For this reason, a reliable
      high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)
      method for the determination of fusarin C in food and feed samples was developed
      based on dispersive solid phase extraction (DSPE). This method has a limit of
      detection (LOD) of 2 MUg/kg, a limit of quantitation (LOQ) of 7 MUg/kg, and a
      recovery rate of 80%. Fifty different corn samples were analyzed, and fusarin C
      was detected in 40 of them. The fusarin C level varied in kernels of corn ears
      from not detectable up to 83 mg/kg and in food samples from not detectable up to
      28 MUg/kg. The co-occurrence of further structural analogues of fusarin C was
      confirmed by high-performance liquid chromatography Fourier transformation mass
      spectrometry (HPLC-FTMS). In addition, the stability of fusarin C under storage
      conditions was evaluated.

PMID- 21894896
TI  - Recent developments in the synthesis of fused sultams.

PMID- 21894897
TI  - Synthesis of biocompatible PEG-Based star polymers with cationic and degradable
      core for siRNA delivery.
AB  - Star polymers with poly(ethylene glycol) (PEG) arms and a degradable cationic
      core were synthesized by the atom transfer radical copolymerization (ATRP) of
      poly(ethylene glycol) methyl ether methacrylate macromonomer (PEGMA), 2
      (dimethylamino)ethyl methacrylate (DMAEMA), and a disulfide dimethacrylate (cross
      linker, SS) via an "arm-first" approach. The star polymers had a diameter ~15 nm
      and were degraded under redox conditions by glutathione treatment into individual
      polymeric chains due to cleavage of the disulfide cross-linker, as confirmed by
      dynamic light scattering. The star polymers were cultured with mouse calvarial
      preosteoblast-like cells, embryonic day 1, subclone 4 (MC3T3-E1.4) to determine
      biocompatibility. Data suggest star polymers were biocompatible, with >= 80% cell
      viability after 48 h of incubation even at high concentration (800 MUg/mL). Zeta
      potential values varied with N/P ratio confirming complexation with siRNA.
      Successful cellular uptake of the star polymers in MC3T3-E1.4 cells was observed
      by confocal microscopy and flow cytometry after 24 h of incubation.

PMID- 21894899
TI  - Synthesis of heterocycles mediated by benzotriazole. 2. Bicyclic systems.

PMID- 21894898
TI  - Pseudoguaianolides and guaianolides from Inula hupehensis as potential anti
      inflammatory agents.
AB  - Eight new pseudoguaianolides (1-8), two new guaianolides (9 and 10), and 14 known
      sesquiterpenes were isolated from the aerial parts of Inula hupehensis. The
      structures were elucidated using spectroscopic methods and circular dichroism
      analysis. All compounds were tested for inhibitory activities against LPS-induced
      nitric oxide production in RAW264.7 macrophages. Compounds 13 and 22 were found
      to inhibit nitric oxide production potently, with IC50 values of 0.9 and 0.6 MUM,
      respectively. Preliminary structure-activity relationships for these compounds
      are proposed.

PMID- 21894900
TI  - Substitutions of coenzyme-binding, nonpolar residues improve the low-temperature
      activity of thermophilic dehydrogenases.
AB  - Although enzymes of thermophilic organisms are often very resistant to thermal
      denaturation, they are usually less active than their mesophilic or psychrophilic
      homologues at moderate or low temperatures. To explore the structural features
      that would improve the activity of a thermophilic enzyme at less than optimal
      temperatures, we randomly mutated the DNA of single-site mutants of the
      thermostable Thermus thermophilus 3-isopropylmalate dehydrogenase that already
      had improved low-temperature activity and selected for additional improved low
      temperature activity. A mutant (Ile279 -> Val) with improved low-temperature
      activity contained a residue that directly interacts with the adenine of the
      coenzyme NAD(+), suggesting that modulation of the coenzyme-binding pocket's
      volume can enhance low-temperature activity. This idea was further supported by a
      saturation mutagenesis study of the two codons of two other residues that
      interact with the adenine. Furthermore, a similar type of amino acid substitution
      also improved the catalytic efficiency of another thermophilic dehydrogenase, T.
      thermophilus lactate dehydrogenase. Steady-state kinetic experiments showed that
      the mutations all favorably affected the catalytic turnover numbers. Thermal
      stability measurements demonstrated that the mutants remain very resistant to
      heat. Calculation of the energetic contributions to catalysis indicated that the
      increased turnover numbers are the result of destabilized enzyme-substrate
      coenzyme complexes. Therefore, small changes in the side chain volumes of
      coenzyme-binding residues improved the catalytic efficiencies of two thermophilic
      dehydrogenases while preserving their high thermal stabilities and may be a way
      to improve low-temperature activities of dehydrogenases in general.

PMID- 21894902
TI  - Meliaceous limonoids: chemistry and biological activities.

PMID- 21894901
TI  - Redefining the minimal substrate tolerance of mandelate racemase. Racemization of
      trifluorolactate.
AB  - Mandelate racemase (EC 5.1.2.2) from Pseudomonas putida catalyzes the
      interconversion of the enantiomers of mandelic acid and a variety of aryl- and
      heteroaryl-substituted mandelate derivatives, suggesting that beta,gamma
      unsaturation is a requisite feature of substrates for the enzyme. We show that
      beta,gamma-unsaturation is not an absolute requirement for catalysis and that
      mandelate racemase can bind and catalyze the racemization of (S)-trifluorolactate
      (k(cat) = 2.5 +/- 0.3 s(-1), K(m) = 1.74 +/- 0.08 mM) and (R)-trifluorolactate
      (k(cat) = 2.0 +/- 0.2 s(-1), K(m) = 1.2 +/- 0.2 mM). The enzyme was shown to
      catalyze hydrogen-deuterium exchange at the alpha-postion of trifluorolactate
      using (1)H NMR spectrocsopy. beta-Elimination of fluoride was not detected using
      (19)F NMR spectroscopy. Although mandelate racemase bound trifluorolactate with
      an affinity similar to that exhibited for mandelate, the turnover numbers
      (k(cat)) were markedly reduced by ~318-fold, resulting in catalytic efficiencies
      (k(cat)/K(m)) that were ~400-fold lower than those observed for mandelate. These
      observations suggested that chemical steps on the enzyme were likely rate
      determining, which was confirmed by demonstrating that the rates of mandelate
      racemase-catalyzed racemization of (S)-trifluorolactate were not dependent upon
      the solvent microviscosity. Circular dichroism spectroscopy was used to measure
      the rates of nonenzymatic racemization of (S)-trifluorolactate at elevated
      temperatures. The values of DeltaH(?) and DeltaS(?) for the nonenzymatic
      racemization reaction were determined to be 28.0 (+/-0.7) kcal/mol and -15.7 (+/
      1.7) cal K(-1) mol(-1), respectively, corresponding to a free energy of
      activation equal to 33 (+/-4) kcal/mol at 25  degrees C. Hence, mandelate
      racemase stabilizes the altered trifluorolactate in the transition state
      (DeltaG(tx)) by at least 20 kcal/mol.

PMID- 21894903
TI  - Impact of temperature on the LB patterning of DPPC on mica.
AB  - The influence of the subphase temperature on the stripe pattern formation during
      Langmuir-Blodgett transfer (LB patterning) is investigated in a combined
      experimental and theoretical study. According to our experiments on the LB
      transfer of dipalmitoylphosphatidylcholine (DPPC) on planar mica substrates, even
      small temperature changes between 21.5 and 24.5  degrees C lead to significant
      changes in the monolayer patterns. For a constant surface pressure and dipper
      speed, the width of the stripes and the overall spatial period of the patterns
      increase with increasing subphase temperature. Because the stripe patterns are
      ascribed to alternating monolayer domains in the liquid-expanded and the liquid
      condensed phases, the working regime for the formation of stripes is found to
      depend strongly on the respective surface pressure-area isotherm. These
      experimental findings are in accordance with the results of a theoretical
      investigation based on a model that takes hydrodynamics and the monolayer
      thermodynamics into account.

PMID- 21894904
TI  - Absolute configuration of 7,8-seco-7,8-oxacassane diterpenoids from Acacia
      schaffneri.
AB  - Chemical investigations of Acacia schaffneri led to the isolation of the new
      diterpenoid (5S,7R,8R,9R,10S)-(-)-7,8-seco-7,8-oxacassa-13,15-diene-7,17-diol
      (1), together with the known (5S,7R,8R,9R,10S)-(-)-7,8-seco-7,8-oxacassa-13,15
      dien-7-ol-17-al (2) and (5S,7R,8R,9R,10S)-(-)-7,8-seco-7,8-oxacassa-13,15-dien-7
      ol (3). Compounds 2 and 3 were analyzed by single-crystal X-ray diffraction,
      while the structure of 1 was determined by 1D and 2D NMR experiments and by
      chemical correlation with 2. Oxidation of 3 afforded conformationally restricted
      (5S,8R,9R,10S)-(-)-8-hydroxy-7,8-seco-cassa-13,15-dien-7-oic acid epsilon-lactone
      (4), which was studied by vibrational circular dichroism spectroscopy. Comparison
      of the experimental VCD spectrum of 4 with the DFT//B3PW91/DGDZVP2 calculated
      spectrum assigned for the first time the absolute configuration of these seco
      oxacassane diterpenes.

PMID- 21894905
TI  - Single-particle mineralogy of Chinese soil particles by the combined use of low-Z
      particle electron probe X-ray microanalysis and attenuated total reflectance-FT
      IR imaging techniques.
AB  - Our previous work on the speciation of individual mineral particles of micrometer
      size by the combined use of attenuated total reflectance FT-IR (ATR-FT-IR)
      imaging and a quantitative energy-dispersive electron probe X-ray microanalysis
      technique (EPMA), low-Z particle EPMA, demonstrated that the combined use of
      these two techniques is a powerful approach for looking at the single-particle
      mineralogy of externally heterogeneous minerals. In this work, this analytical
      methodology was applied to characterize six soil samples collected at arid areas
      in China, in order to identify mineral types present in the samples. The six soil
      samples were collected from two types of soil, i.e., loess and desert soils, for
      which overall 665 particles were analyzed on a single particle basis. The six
      soil samples have different mineralogical characteristics, which were clearly
      differentiated in this work. As this analytical methodology provides
      complementary information, the ATR-FT-IR imaging on mineral types, and low-Z
      particle EPMA on the morphology and elemental concentrations, on the same
      individual particles, more detailed information can be obtained using this
      approach than when either low-Z particle EPMA or ATR-FT-IR imaging techniques are
      used alone, which has a great potential for the characterization of Asian dust
      and mineral dust particles.

PMID- 21894906
TI  - Fate of endogenous steroid hormones in steer feedlots under simulated rainfall
      induced runoff.
AB  - Steroid hormones pose potential risks to fish and other aquatic organisms at
      extremely low concentrations. To assess the factors affecting the release of
      endogenous estrogenic and androgenic steroids from feedlots during rainfall,
      runoff, and soil samples were collected after simulated rainfall on a 14-steer
      feedlot under different rainfall rates and aging periods and analyzed for six
      steroid hormones. While only 17alpha-estradiol, testosterone, and progesterone
      were detected in fresh manure, 17beta-estradiol, estrone, and androstenedione
      were present in the surficial soil after two weeks. In the feedlot surficial
      soil, concentrations of 17alpha-estradiol decreased by approximately 25%
      accompanied by an equivalent increase in estrone and 17beta-estradiol. Aging of
      the feedlot soils for an additional 7 days had no effect on estrogen and
      testosterone concentrations, but androstenedione concentrations decreased
      substantially, and progesterone concentrations increased. Androstenedione and
      progesterone concentrations in the surficial soil were much higher than could be
      accounted for by excretion or conversion from testosterone, suggesting that other
      potential precursors, such as sterols, were converted after excretion. The
      concentration of androgens and progesterone in the soil were approximately 85%
      lower after simulated rainfall, but the estrogen concentrations remained
      approximately constant. The decreased masses could not be accounted for by
      runoff, suggesting the possibility of rapid microbial transformation upon
      wetting. All six steroids in the runoff, with the exception of 17beta-estradiol,
      were detected in both the filtered and particle-associated phases at
      concentrations well above thresholds for biological responses. Runoff from the
      aged plots contained less 17alpha-estradiol and testosterone, but more estrone,
      androstenedione, and progesterone relative to the runoff from the unaged plots,
      and most of the steroids had a lower particle-associated fraction.

PMID- 21894907
TI  - The REDD market should not end up a subprime house of cards: introducing a new
      REDD architecture for environmental integrity.

PMID- 21894908
TI  - Comment on Water droplet motion control on superhydrophobic surfaces: exploiting
      the Wenzel-to-Cassie transition.

PMID- 21894909
TI  - N-terminal protein modification using simple aminoacyl transferase substrates.
AB  - Methods for synthetically manipulating protein structure enable greater
      flexibility in the study of protein function. Previous characterization of the
      Escherichia coli aminoacyl tRNA transferase (AaT) has shown that it can modify
      the N-terminus of a protein with an amino acid from a tRNA or a synthetic
      oligonucleotide donor. Here, we demonstrate that AaT can efficiently use a
      minimal adenosine substrate, which can be synthesized in one to two steps from
      readily available starting materials. We have characterized the enzymatic
      activity of AaT with aminoacyl adenosyl donors and found that reaction products
      do not inhibit AaT. The use of adenosyl donors removes the substrate limitations
      imposed by the use of synthetases for tRNA charging and avoids the complex
      synthesis of an oligonucleotide donor. Thus, our AaT donors increase the
      potential substrate scope and reaction scale for N-terminal protein modification
      under conditions that maintain folding.

PMID- 21894911
TI  - Ligand binding intermediates of nitrosylated human hemoglobin induced at low
      temperature by X-ray irradiation.
AB  - Under prolonged X-ray irradiation, the ferrous heme of nitrosylated human adult
      hemoglobin derivative (HbNO) undergoes a reversible transition generating a 5
      coordinate species, due to release of the Fe-NO bond. The overall process can be
      investigated using X-ray absorption near edge structure (XANES) spectroscopy. In
      this work, Fe K-edge XANES spectra were measured at T < 15 K, pH 9.2, i.e., on a
      high-affinity state (R-HbNO) where all the hemes are 6-coordinate, and at pH 6.5
      in the presence of inositol hexakis-phosphate (IHP), i.e., on a low-affinity
      ligated state (T-HbNO) where the iron-hemes of the alpha-chains are 5-coordinate
      due to breaking of the Fe-proximal histidine bond. Under X-ray irradiation, 5
      coordinate Fe-hemes are populated in both R-HbNO and T-HbNO, the Fe-NO bond lysis
      induced in T-HbNO involving rebinding of the proximal histidine to the
      transiently populated 4-coordinate hemes of the alpha-chains. A detailed analysis
      of the spectra confirms that different intermediate states in the ligand binding
      cooperative process of hemoglobin can be populated by X-ray irradiation, and that
      the part of the energy associated to the R-T quaternary transition, that is
      transmitted to the heme site, can be monitored by XANES spectroscopy.

PMID- 21894910
TI  - Divergence of structure and function in the haloacid dehalogenase enzyme
      superfamily: Bacteroides thetaiotaomicron BT2127 is an inorganic pyrophosphatase.
AB  - The explosion of protein sequence information requires that current strategies
      for function assignment evolve to complement experimental approaches with
      computationally based function prediction. This necessitates the development of
      strategies based on the identification of sequence markers in the form of
      specificity determinants and a more informed definition of orthologues. Herein,
      we have undertaken the function assignment of the unknown haloalkanoate
      dehalogenase superfamily member BT2127 (Uniprot accession code Q8A5 V9) from
      Bacteroides thetaiotaomicron using an integrated bioinformatics-structure
      mechanism approach. The substrate specificity profile and steady-state rate
      constants of BT2127 (with a k(cat)/K(m) value for pyrophosphate of ~1 * 10(5) M(
      1) s(-1)), together with the gene context, support the assigned in vivo function
      as an inorganic pyrophosphatase. The X-ray structural analysis of wild-type
      BT2127 and several variants generated by site-directed mutagenesis shows that
      substrate discrimination is based, in part, on active site space restrictions
      imposed by the cap domain (specifically by residues Tyr76 and Glu47). Structure
      guided site-directed mutagenesis coupled with kinetic analysis of the mutant
      enzymes identified the residues required for catalysis, substrate binding, and
      domain-domain association. On the basis of this structure-function analysis, the
      catalytic residues Asp11, Asp13, Thr113, and Lys147 as well the metal binding
      residues Asp171, Asn172, and Glu47 were used as markers to confirm BT2127
      orthologues identified via sequence searches. This bioinformatic analysis
      demonstrated that the biological range of BT2127 orthologue is restricted to the
      phylum Bacteroidetes/Chlorobi. The key structural determinants in the divergence
      of BT2127 and its closest homologue, beta-phosphoglucomutase, control the leaving
      group size (phosphate vs glucose phosphate) and the position of the Asp acid/base
      in the open versus closed conformations. HADSF pyrophosphatases represent a third
      mechanistic and fold type for bacterial pyrophosphatases.

PMID- 21894912
TI  - Luminescent rhenium(I) polypyridine fluorous complexes as novel trifunctional
      biological probes.
AB  - We present the synthesis, characterization, and photophysical properties of three
      luminescent rhenium(I) polypyridine fluorous complexes
      [Re(Me(2)bpy)(CO)(3)(L)](PF(6)) (Me(2)bpy = 4,4'-dimethyl-2,2'-bipyridine; L = 3
      amino-5-(N-((3-perfluorooctyl)propyl)aminocarbonyl)pyridine (py-Rf-NH(2)) (1), 3
      isothiocyanato-5-(N-((3-perfluorooctyl)propyl)aminocarbonyl)pyridine (py-Rf-NCS)
      (2), 3-ethylthioureidyl-5-(N-((3-perfluorooctyl)propyl)aminocarbonyl)pyridine (py
      Rf-TU-C(2)H(5)) (3)). The isothiocyanate complex 2 has been used to label bovine
      serum albumin (BSA) and glutathione (GSH). The photophysical properties of the
      resultant bioconjugates have been studied. The isolation of the luminescent
      fluorous rhenium-GSH conjugate from a mixture of 20 amino acids has been
      demonstrated using fluorous solid-phase extraction (FSPE). Additionally, the
      cytotoxicity of complexes 1 and 3 toward HeLa cells has been examined by the 3
      (4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The
      cellular uptake properties of complex 3 have also been investigated by laser
      scanning confocal microscopy.

PMID- 21894914
TI  - Effect of fruit ripening on content and chemical composition of oil from three
      oil palm cultivars (Elaeis guineensis Jacq.) grown in Colombia.
AB  - A series of physical and chemical changes occur as oil palm fruits ripen in the
      bunch. We evaluated changes in lipid content in the mesocarp and fruits, and the
      chemical composition of fatty acids (FA), triacylglycerol (TAG), tocols, and
      carotenes of the lipids extracted from fruits of three commercial tenera
      cultivars, namely, Deli*La Me, Deli*Ekona, and Deli*Avros, planted in two
      different geographical regions in Colombia, during the ripening process 12, 14,
      16, 18, 20, 22, and 24 weeks after anthesis (WAA). It was found that 12 WAA the
      mesocarp contained less than 6% of total lipids. Oil content increased rapidly
      after 16 WAA, reaching the maximum oil content of 55% in fresh mesocarp and 47%
      in fresh fruits at 22 WAA, which was found the optimal time for harvesting.
      Changes in FA and TAG showed that total polyunsaturated fatty acids (PUFA) and
      triunsaturated triacylglycerols (TUTAG) decreased, while total saturated fatty
      acids (SFA) and disaturated triacylglycerols (DSTAG) increased, over the ripening
      period. Changes in FA were mainly observed in palmitic, oleic, linoleic, and
      linolenic acids, and in POP, POO, POL, and OLL for the TAGs evaluated. Levels of
      tocols changed depending on whether they were tocopherols or tocotrienols. In the
      earliest stages tocopherols were predominant but decreased rapidly from 6600 mg
      kg(-1) of oil at 14 WAA to 93 mg kg(-1) of oil at 22 WAA. Tocotrienols appeared
      at the same time as oil synthesis started, and became the main source of total
      tocols, equivalent to 87% in total lipids extracted.

PMID- 21894913
TI  - Direct entry to erythronolides via a cyclic bis[allene].
AB  - The complexity and low tractability of antibiotic macrolides pose serious
      challenges to addressing the problem of resistance through semi- or total
      synthesis. Here we describe a new strategy involving the preparation of a complex
      yet tractable macrocycle and the transformation of this macrocycle into a range
      of erythronolide congeners. These compounds represent valuable sectors of
      erythromycinoid structure space and constitute intermediates with the potential
      to provide further purchase in this space. The routes are short. The
      erythronolides were prepared in three or fewer steps from the macrocycle, which
      was prepared in a longest linear sequence of 11 steps.

PMID- 21894916
TI  - Children's exposure to Di(2-ethylhexyl)phthalate and dibutylphthalate
      plasticizers from school meals.
AB  - Packed school meals for children 3-10 years old were studied to evaluate the
      levels of di(2-ethylhexyl)phthalate (DEHP) and di-n-butylphthalate (DBP) and the
      influence of the packaging process on meal contamination, and their contribution
      to daily intake was estimated. The packaging consisted of polyethylene-coated
      aluminum (PE/Al) dishes thermally welded by a polyethyleneterephthalate-coated
      aluminum (PET/Al) foil. Foodstuffs before processing were analyzed, too. Total
      meals before packaging and after packaging were collected. It was found that 92%
      of foodstuffs employed in meal preparation contained DEHP, and 76% of them DBP,
      at detectable levels. In cooked foods before packaging the DEHP median
      concentration levels varied from 111.4 to 154.8 ng/g ww and those of DBP between
      32.5 and 59.5 ng/g ww. In packed meals the DEHP median values ranged from 127.0
      to 253.3 ng/g ww, and DBP median values varied from 44.1 to 80.5 ng/g ww. The
      mean increases of median concentrations of DEHP in cooked foods before and after
      packaging were 113 and 125% for DBP. For nursery and primary school children DEHP
      intake via school meals can raise on average the respective EFSA TDI by 18 and
      12% and that of DBP by 50 and 30%.

PMID- 21894917
TI  - Ditantalum dinitrogen complex: reaction of H2 molecule with "end-on-bridged"
      [Ta(IV)]2(MU-eta(1):eta(1)-N2) and Bis(MU-nitrido) [Ta(V)]2(MU-N)2 complexes.
AB  - To elucidate (i) the physicochemical properties of the {(eta(5)
      C(5)Me(5))[Ta(IV)](i-Pr)C(Me)N(i-Pr)}(2)(MU-eta(1):eta(1)-N(2)), I,
      [Ta(IV)](2)(MU-eta(1):eta(1)-N(2)), and {(eta(5)-C(5)Me(5))[Ta(V)](i-Pr)C(Me)N(i
      Pr)}(2)(MU-N)(2), II, [Ta(V)](2)(MU-N)(2), complexes; (ii) the mechanism of the I
      -> II isomerization; and (iii) the reaction mechanism of these complexes with an
      H(2) molecule, we launched density functional (B3LYP) studies of model systems 1,
      2, and 3 where the C(5)Me(5) and (i-Pr)C(Me)N(i-Pr) ligands of I (or II) were
      replaced by C(5)H(5) and HC(NCH(3))(2), respectively. These calculations show
      that the lower-lying electronic states of 1, [Ta(IV)](2)(MU-eta(1):eta(1)-N(2)),
      are nearly degenerate open-shell singlet and triplet states with two unpaired
      electrons located on the Ta centers. This finding is in reasonable agreement with
      experiments [J. Am Chem. Soc. 2007, 129, 9284-9285] showing easy accessibility of
      paramagnetic and diamagnetic states of I. The ground electronic state of the
      bis(MU-nitrido) complex 2, [Ta(V)](2)(MU-N)(2), is a closed-shell singlet state
      in agreement with the experimentally reported diamagnetic feature of II. The 1-to
      2 rearrangement is a multistep and highly exothermic process. It occurs with a
      maximum of 28.7 kcal/mol free energy barrier required for the (MU-eta(1):eta(1)
      N(2)) -> (MU-eta(2):eta(2)-N(2)) transformation step. Reaction of 1 with H(2)
      leading to the 1,4-addition product 3 proceeds with a maximum of 24.2 kcal/mol
      free energy barrier associated by the (MU-eta(1):eta(1)-N(2)) -> (MU
      eta(2):eta(1)-N(2)) isomerization step. The overall reaction 1 + H(2) -> 3 is
      exothermic by 20.0 kcal/mol. Thus, the addition of H(2) to 1 is kinetically and
      thermodynamically feasible and proceeds via the rate-determining (MU
      eta(1):eta(1)-N(2)) -> (MU-eta(2):eta(1)-N(2)) isomerization step. The bis(MU
      nitrido) complex 2, [Ta(V)](2)(MU-N)(2), does not react with H(2) because of the
      large energy barrier (49.5 kcal/mol) and high endothermicity of the reaction.
      This conclusion is also in excellent agreement with the experimental observation
      [J. Am Chem. Soc. 2007, 129, 9284-9285].

PMID- 21894918
TI  - Mass spectrometric and theoretical study of polyiodides: the connection between
      solid state, solution, and gas phases.
AB  - Polyiodides have been transferred intact from acetonitrile solution to the gas
      phase and analyzed by mass spectrometry. A range of ions were observed, including
      [I(11)](-), [I(13)](-), and [I(15)](-), which have higher iodine/iodide ratios
      than any previously characterized ions. Theoretical calculations show that
      branched structures are strongly favored, a result which is in excellent
      agreement with with gas phase fragmentation studies (MS/MS) and also previous
      solid state studies. This study demonstrates the utility of mass spectrometry to
      provide structural information in the absence of other spectroscopic handles.

PMID- 21894919
TI  - Structure of complexes formed by dissolution of palladium diacetate in methanol
      and chloroform. In situ NMR study.
AB  - The behavior of palladium diacetate cyclic trimer [Pd(OAc)(2)](3) (1) upon its
      dissolution in methanol and wet chloroform was studied by (1)H and (13)C NMR
      including 2D-HSQC and 2D-DOSY techniques. Upon dissolution, trimer 1 reacts with
      methanol and is completely transformed first into the methoxo complex Pd(3)(MU
      OMe)(OAc)(5) (2), which already at -18  degrees C undergoes a slow exchange of
      second bridging acetate ligand between the same palladium atoms to form the
      symmetric dimethoxo complex Pd(3)(MU-OMe)(2)(OAc)(4), the maximum relative
      concentration of which reaches 20-30 mol % of initial loading trimer 1. Along
      with the dimethoxo complex, both soluble and insoluble polynuclear palladium
      clusters are gradually formed at -18  degrees C, and their total amount reaches
      up to 60% of the starting Pd(2+) loading. The increase of temperature to 27 
      degrees C results in the reduction of palladium(II) to Pd metal by methanol,
      which is oxidized and transformed into formaldehyde hemiacetal and methyl
      formate. Upon dissolution in wet chloroform, trimer 1 is reversibly hydrolyzed to
      the hydroxo complex Pd(3)(MU-OH)(OAc)(5) (10) in ratio 1/10 ~ 3/1. The
      temperature decrease and addition of acetic acid shift the equilibrium in this
      system toward trimer 1, and addition of water shifts it in the opposite
      direction. Addition of methanol to the equilibrium mixture of 1 and 10 results in
      the fast exchange of bridging acetate in trimer 1 by the MU-OMe group.
      Substitution of the MU-OH ligand by MU-OMe in 10 occurs in parallel but more
      slowly. Complex 2 formed in both cases is more stable in chloroform than in
      methanol.

PMID- 21894920
TI  - Electronic structure and bonding in heteronuclear dimers of V, Cr, Mo, and W: a
      CASSCF/CASPT2 study.
AB  - Heteronuclear dimers like CrMo, CrW, MoW, VCr, VMo, VW, and their anions have
      been investigated by means of multiconfigurational quantum chemistry methods,
      using the complete active space self-consistent field followed by second-order
      perturbation theory, CASSCF/CASPT2. We explored in great detail several
      spectroscopic properties such as bond length, potential energy surfaces,
      dissociation energies, ionization potentials, electron affinities, low-lying
      excited states, vibrational frequencies, and dipole moments. All proposed dimers
      show ground states with a pronounced multireference character. The group VI
      heterodimers have a (1)Sigma(+) ground state, while the mixed group V-group VI
      heterodimers show a (2)Delta ground state. Among all dimers, only VCr presents a
      potential energy profile with a deep minimum in the d-d region and a shelf-like
      potential in the s-s region. All the remaining dimers show only the short-range
      minimum. The largest effective bond order is obtained for the MoW, with a value
      of 5.2, that is, a weak sextuple bond. Most of the obtained results are valuable
      tools to drive future experimental investigations.

PMID- 21894922
TI  - Analogues of the Lavallo-Grubbs compound Fe3(C8H8)3: equilateral, isosceles, and
      scalene metal triangles in trinuclear cyclooctatetraene complexes M3(C8H8)3 of
      the first row transition metals (M = Ti, V, Cr, Mn, Fe, Co, and Ni).
AB  - The trinuclear derivative Fe(3)(C(8)H(8))(3) was synthesized in 2009 by Lavallo
      and Grubbs via the reaction of Fe(C(8)H(8))(2) with a bulky heterocyclic carbene.
      This fascinating structure is the first example of a derivative of the well-known
      Fe(3)(CO)(12) in which all 12 carbonyl groups have been replaced by hydrocarbon
      ligands. The density functional theory predicts a structure having a central
      Fe(3) equilateral triangle with ~2.9 A Fe-Fe single bonded edges bridged by
      eta(5),eta(3)-C(8)H(8) ligands. This structure is close to the experimental
      structure, determined by X-ray crystallography. The related hypoelectronic
      M(3)(C(8)H(8))(3) derivatives (M = Cr, V, Ti) are predicted to have central
      scalene M(3) triangles with edge lengths and Wiberg bond indices (WBIs)
      corresponding to one formal single M-M bond, one formal double M?M bond, and one
      formal triple M=M bond. For Mn(3)(C(8)H(8))(3), both a doublet structure with one
      Mn?Mn double bond and two Mn-Mn single bonds in the Mn(3) triangle, and a quartet
      structure with two Mn?Mn double bonds and one Mn-Mn single bond are predicted.
      The hyperelectronic derivatives M(3)(C(8)H(8))(3) have weaker direct M-M
      interactions in their M(3) triangles, as indicated by both the M-M distances and
      the WBIs. Thus, Ni(3)(C(8)H(8))(3) has bis(trihapto) eta(3),eta(3)-C(8)H(8)
      ligands bridging the edges of a central approximately equilateral Ni(3) triangle
      with long Ni...Ni distances of ~3.7 A. The WBIs indicate very little direct Ni-Ni
      bonding in this Ni(3) triangle and thus a local nickel environment in the singlet
      Ni(3)(C(8)H(8))(3) similar to that observed for diallylnickel (eta(3)
      C(3)H(5))(2)Ni.

PMID- 21894921
TI  - Nature of halide binding to the molybdenum site of sulfite oxidase.
AB  - Valuable information on the active sites of molybdenum enzymes has been provided
      from both Mo(V) electron paramagnetic resonance (EPR) spectroscopy and X-ray
      absorption spectroscopy (XAS). One of three major categories of Mo(V) EPR signals
      from the molybdenum enzyme sulfite oxidase is the low-pH signal, which forms in
      the presence of chloride. Two alternative structures for this species have been
      proposed, one in which the chloride is coordinated directly to Mo and a second in
      which chloride is held in the arginine-rich basic pocket some 5 A from Mo. Here
      we present an independent assessment of the structure of this species by using
      XAS of the analogous bromide and iodide complexes. We show that there is no
      evidence of direct Mo-I coordination, and that the data are consistent with a
      structure in which the halide is bound at ~5 A from Mo.

PMID- 21894923
TI  - Limited occurrence of isocloso deltahedra with 9 to 12 vertices in low-energy
      hypoelectronic diferradicarbaborane structures.
AB  - Theoretical studies show that the 10-vertex system Cp(2)Fe(2)C(2)B(6)H(8) is the
      only one of the 2n skeletal electron Cp(2)Fe(2)C(2)B(n-4)H(n-2) systems (n = 9,
      10, 11, 12) for which a true isocloso deltahedron having a single degree 6 vertex
      is highly favored over alternative structures. This is demonstrated by the
      occurrence of only the 10-vertex isocloso deltahedron as the central
      Fe(2)C(2)B(6) polyhedron in all nine of the Cp(2)Fe(2)C(2)B(6)H(8) structures
      within 8 kcal/mol of the global minimum. Low energy isocloso structures are also
      observed for the 11-vertex Cp(2)Fe(2)C(2)B(7)H(9). However, interspersed with
      these isocloso structures are Cp(2)Fe(2)C(2)B(7)H(9) structures based on
      deltahedra having two or more degree 6 vertices. For the 12-vertex
      Cp(2)Fe(2)C(2)B(8)H(10), the six lowest energy structures all have central
      Fe(2)C(2)B(8) deltahedra with two degree 6 vertices, one for each iron atom. The
      Cp(2)Fe(2)C(2)B(8)H(10) structures having a central Fe(2)C(2)B(8) icosahedron
      with all degree 5 vertices lie at significantly higher energies, starting at 17.8
      kcal/mol above the global minimum. The 9-vertex Cp(2)Fe(2)C(2)B(5)H(7) system
      appears to be too small for isocloso structures to be favorable, although three
      such structures are found at energies between 5.5 and 8.0 kcal/mol above the
      global minimum. Five Cp(2)Fe(2)C(2)B(5)H(7) structures based on the tricapped
      trigonal prism lie in an energy below the lowest energy isocloso structure. The
      lowest energy Cp(2)Fe(2)C(2)B(5)H(7) structure and two higher energy structures
      within 8.0 kcal/mol of the global minimum have central Fe(2)C(2)B(5) deltahedra
      with a degree 6 vertex for each iron atom.

PMID- 21894924
TI  - What is the shape of the helium trimer? A comparison with the neon and argon
      trimers.
AB  - Despite its apparent simplicity and extensive theoretical investigations, the
      issue of what is the shape of the helium trimer is still debated in the
      literature. After reviewing previous conflicting interpretations of computational
      studies, we introduce the angle-angle distribution function as a tool to discuss
      in a simple way the shape of any trimer. We compute this function along with many
      different geometrical distributions using variational and diffusion Monte Carlo
      methods. We compare them with the corresponding ones for the neon and argon
      trimers. Our analysis shows that while Ne(3) and Ar(3) fluctuate around an
      equilibrium structure that is an equilateral triangle, (4)He(3) shows an
      extremely broad angle-angle distribution function, and all kinds of three-atom
      configurations must be taken into account in its description. Classifying
      (4)He(3) as either equilateral or linear or any other particular shape, as was
      done in the past, is not sensible, because in this case the intuitive notion of
      equilibrium structure is ill defined. Our results could help the interpretation
      of future experiments aimed at measuring the geometrical properties of the helium
      trimer.

PMID- 21894925
TI  - Accumulation of microplastic on shorelines woldwide: sources and sinks.
AB  - Plastic debris <1 mm (defined here as microplastic) is accumulating in marine
      habitats. Ingestion of microplastic provides a potential pathway for the transfer
      of pollutants, monomers, and plastic-additives to organisms with uncertain
      consequences for their health. Here, we show that microplastic contaminates the
      shorelines at 18 sites worldwide representing six continents from the poles to
      the equator, with more material in densely populated areas, but no clear
      relationship between the abundance of miocroplastics and the mean size
      distribution of natural particulates. An important source of microplastic appears
      to be through sewage contaminated by fibers from washing clothes. Forensic
      evaluation of microplastic from sediments showed that the proportions of
      polyester and acrylic fibers used in clothing resembled those found in habitats
      that receive sewage-discharges and sewage-effluent itself. Experiments sampling
      wastewater from domestic washing machines demonstrated that a single garment can
      produce >1900 fibers per wash. This suggests that a large proportion of
      microplastic fibers found in the marine environment may be derived from sewage as
      a consequence of washing of clothes. As the human population grows and people use
      more synthetic textiles, contamination of habitats and animals by microplastic is
      likely to increase.

PMID- 21894926
TI  - Using high intensity ultrasound as a tool to change the functional properties of
      interesterified soybean oil.
AB  - High intensity ultrasound (HIU) was used to change the crystallization behavior,
      generate small crystals, and improve the texture of a low saturated shortening
      (interesterified soybean oil). Samples were crystallized at different
      temperatures (26, 28, 30, and 32  degrees C) without and with the application of
      HIU. Different acoustic power levels (110, 72, 61, 54, and 44 W) were used.
      Results show that higher acoustic powers had a greater effect on crystal size
      reduction, induced crystallization, and generated harder, more elastic and
      viscous materials. These effects were more significant when HIU was applied in
      the presence of crystals and when the sample was crystallized at 32  degrees C.

PMID- 21894927
TI  - Anharmonic frequencies of CX2Y2 (X, Y = O, N, F, H, D) isomers and related
      systems obtained from vibrational multiconfiguration self-consistent field
      theory.
AB  - Accurate anharmonic frequencies are provided for molecules of current research,
      i.e., diazirines, diazomethane, the corresponding fluorinated and deuterated
      compounds, their dioxygen analogs, and others. Vibrational-state energies were
      obtained from state-specific vibrational multiconfiguration self-consistent field
      theory (VMCSCF) based on multilevel potential energy surfaces (PES) generated
      from explicitly correlated coupled cluster, CCSD(T)-F12a, and double-hybrid
      density functional calculations, B2PLYP. To accelerate the vibrational structure
      calculations, a configuration selection scheme as well as a polynomial
      representation of the PES have been exploited. Because experimental data are
      scarce for these systems, many calculated frequencies of this study are
      predictions and may guide experiments to come.

PMID- 21894928
TI  - Understanding the synergistic effect of arginine and glutamic acid mixtures on
      protein solubility.
AB  - Understanding protein solubility is a key part of physical chemistry. In
      particular, solution conditions can have a major effect, and the effect of
      multiple cosolutes is little understood. It has been shown that the simultaneous
      addition of L-arginine hydrochloride and L-glutamic acid enhances the maximum
      achievable solubility of several poorly soluble proteins up to 4-8 times
      (Golovanov et. al, J. Am. Chem. Soc., 2004, 126, 8933-8939) and reduces the
      intermolecular interactions between proteins. The observed solubility enhancement
      is negligible for arginine and glutamic acid solutions as compared to the
      equimolar mixtures. In this study, we have established the molecular mechanism
      behind this observed synergistic effect of arginine and glutamic acid mixtures
      using preferential interaction theory and molecular dynamics simulations of
      Drosophilia Su(dx) protein (ww34). It was found that the protein solubility
      enhancement is related to the relative increase in the number of arginine and
      glutamic acid molecules around the protein in the equimolar mixtures due to
      additional hydrogen bonding interactions between the excipients on the surface of
      the protein when both excipients are present. The presence of these additional
      molecules around the protein leads to enhanced crowding, which suppresses the
      protein association. These results highlight the role of additive-additive
      interaction in tuning the protein-protein interactions. Furthermore, this study
      reports a unique behavior of additive solutions, where the presence of one
      additive in solution affects the concentration of another on the protein surface.

PMID- 21894929
TI  - Mapping unstructured regions and synergistic folding in intrinsically disordered
      proteins with amide H/D exchange mass spectrometry.
AB  - Mapping the structured and disordered regions and identifying disorder-to-order
      transitions are essential to understanding intrinsically disordered proteins
      (IDPs). One technique that can provide such information is H/D exchange coupled
      with mass spectrometry (H/D-MS). To explore the feasibility of H/D-MS for mapping
      disordered and ordered regions in IDPs, we undertook a systematic evaluation of
      an unstructured protein, a molten globular protein, and the well-folded complex
      of the two proteins. Most segments of the unstructured protein, ACTR (activator
      of thyroid and retinoid receptors, NCOA3_HUMAN, residues 1018-1088), exchange at
      rates consistent with its assignment as an unstructured protein, but there is
      slight protection in regions that become helical in the ACTR-CBP complex. The
      molten globular protein, CBP (the nuclear coactivator binding domain of the CREB
      binding protein, CBP_MOUSE, residues 2059-2117), is moderately protected from
      exchange, and the protection is nearly uniform across the length of the protein.
      The uniformity arises because of rapid interconversion between an ensemble of
      folded conformers and an ensemble of unstructured conformers. Rapid
      interconversion causes the H/D exchange kinetics to be dominated by exchange by
      molecules in unstructured conformations. For the folded ACTR-CBP complex, the
      exchange data provide a qualitatively accurate description of the complex. Our
      results provide a useful framework to use in the interpretation of H/D-MS data of
      intrinsically disordered proteins.

PMID- 21894930
TI  - Sudden, "step" electron capture by conjugated polymers.
AB  - Data showing significant time-resolution-limited "step" capture of electrons
      following radiolysis by 7 - 10 ps electron pulses in a series of different length
      and different concentration conjugated polyfluorene polymers in tetrahydrofuran
      (THF) are presented. At the highest concentration, ~48 mM in repeat units for
      lengths from 20 to 133 fluorenes, ~30% of the electrons formed during pulse
      radiolysis were captured in the step, with a constant efficiency per repeat unit.
      Step capture per repeat unit (q = 6.9 M(-1)) is 60% of the presolvated electron
      capture efficiency previously reported for biphenyl in THF, giving capture per
      polymer molecule 12-80 times larger than that for biphenyl at the same
      concentration. This increase in capture efficiency is large compared to the rate
      constant per repeat unit for diffusion-limited electron attachment to the same
      molecules, which is 13% of that of a single unit of fluorene. Plausible
      mechanisms of this fast capture are explored. It is shown that both capture of
      quasi-free and localized presolvated electrons can adequately explain the
      observations. The large yield of radical anions at low concentration of
      polyfluorene enables observation of subsequent chemistry on the picosecond time
      scale in these systems, which would otherwise been limited by diffusional
      attachment to the nanosecond regime.

PMID- 21894931
TI  - Oxidation of annelated diarylamines: analysis of reaction pathways to nitroxide
      diradical and spirocyclic products.
AB  - Oxidation of diaryldiamine 2, a tetrahydrodiazapentacene derivative, provides
      diarylnitroxide diradical 1 accompanied by an intermediate nitroxide monoradical
      and a multitude of isolable diamagnetic products. DFT-computed tensors for EPR
      spectra and paramagnetic (1)H NMR isotropic shifts for nitroxide diradical 1 show
      good agreement with the experimental EPR spectra in rigid matrices and
      paramagnetic (1)H NMR spectra in solution, respectively. Examination of the
      diamagnetic products elucidates their formation via distinct pathways involving C
      O bond-forming reactions, including Baeyer-Villiger-type oxidations. An unusual
      diiminoketone structure and two spirocyclic structures of the predominant
      diamagnetic products are confirmed by either X-ray crystallography or
      correlations between DFT-computed and experimental spectroscopic data such as
      (1)H, (13)C, and (15)N NMR chemical shifts and electronic absorption spectra.

PMID- 21894932
TI  - Symmetric and asymmetric bolaamphiphiles from ascorbic acid.
AB  - The properties of novel bolaamphiphiles that carry epimers of vitamin C (L
      ascorbic acid and/or D-isoascorbic acid) as hydrophilic head groups, and an
      interconnecting aliphatic C(12) chain (DD, DL, and LL) were investigated by
      differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), small
      angle X-ray scattering (SAXS), X-ray diffraction (XRD), and Fourier transform
      infrared spectroscopy (FTIR) in the solid state (anhydrous powders) and in
      aqueous dispersions as a function of the surfactant concentration. Upon heating,
      the aqueous dispersions undergo a phase transition from a hydrated
      semicrystalline "coagel" to a micellar phase. The results suggest that the
      headgroup chirality determines the formation of either inter- or intramolecular
      hydrogen bonds between the polar heads, which affect the phase behavior and
      structural properties of the nanoassemblies produced by these surfactants in
      water dispersions. The DSC data of aqueous dispersions were analyzed to obtain
      the size distribution of the pores in the coagel state.

PMID- 21894933
TI  - Salt effects on condensed protamine-DNA assemblies: anion binding and weakening
      of attraction.
AB  - Using osmotic stress coupled with X-ray scattering, we have directly examined the
      salt sensitivity of the intermolecular forces between helices in condensed
      protamine-DNA arrays. Thermodynamic forces are measured from the dependence of
      DNA helical interaxial spacings on external salt concentration or the osmotic
      pressure applied by neutral polymer solutions in equilibrium with the condensed
      phase. Force curves of salmon protamine-DNA condensates are highly dependent on
      salt species and concentration, indicating salt binding to protamine-DNA
      complexes. This dependence of the forces on salt species follows the Hofmeister
      series for anions. Chaotropic anions bind more tightly to protamine-DNA arrays
      than kosmotropic anions, thus more greatly disrupting the attractive
      thermodynamic forces. Variations with cation type are small compared with those
      observed for anions. Further, osmotic stress is used to estimate the number of
      ions bound in the condensed phase through a Gibbs-Duhem relationship. We estimate
      that at equilibrium, ~1 Br(-) is bound per protamine molecule at 200 mM NaBr
      concentration. Remarkably, this one bound anion results in a change of ~12% in
      the surface-to-surface distance between DNA helices. Potential biological
      implications of this attractive force salt sensitivity are discussed.

PMID- 21894934
TI  - Diazo reagents with small steric footprints for simultaneous arming/SAR studies
      of alcohol-containing natural products via O-H insertion.
AB  - Natural products are essential tools for basic cellular studies leading to the
      identification of medically relevant protein targets and the discovery of
      potential therapeutic leads. The development of methods that enable mild and
      selective derivatization of natural products continues to be of significant
      interest for mining their information-rich content. Herein, we describe novel
      diazo reagents for simultaneous arming and structure-activity relationship (SAR)
      studies of alcohol-containing natural products with a small steric footprint,
      namely, an alpha-trifluoroethyl (HTFB) substituted reagent. The Rh(II)-catalyzed
      O-H insertion reaction of several natural products, including the potent
      translation inhibitor lactimidomycin, was investigated, and useful reactivity and
      both chemo- and site (chemosite) selectivities were observed. Differential
      binding to the known protein targets of both FK506 and fumagillol was
      demonstrated, validating the advantage of the smaller steric footprint of alpha
      trifluoroethyl derivatives. A p-azidophenyl diazo reagent is also described that
      will prove useful for photoaffinity labeling of low affinity small molecule
      protein receptors.

PMID- 21894935
TI  - Core-shell MoO3-MoS2 nanowires for hydrogen evolution: a functional design for
      electrocatalytic materials.
AB  - We synthesize vertically oriented core-shell nanowires with substoichiometric
      MoO(3) cores of ~20-50 nm and conformal MoS(2) shells of ~2-5 nm. The core-shell
      architecture, produced by low-temperature sulfidization, is designed to utilize
      the best properties of each component material while mitigating their
      deficiencies. The substoichiometric MoO(3) core provides a high aspect ratio
      foundation and enables facile charge transport, while the conformal MoS(2) shell
      provides excellent catalytic activity and protection against corrosion in strong
      acids.

PMID- 21894936
TI  - Modulating resonance modes and Q value of a CdS nanowire cavity by single Ag
      nanoparticles.
AB  - Semiconductor nanowire (NW) cavities with tailorable optical modes have been used
      to develop nanoscale oscillators and amplifiers in microlasers, sensors, and
      single photon emitters. The resonance modes of NW could be tuned by different
      boundary conditions. However, continuously and reversibly adjusting resonance
      modes and improving Q-factor of the cavity remain a great challenge. We report a
      method to modulate resonance modes continuously and reversibly and improve Q
      factor based on surface plasmon-exciton interaction. By placing single Ag
      nanoparticle (NP) nearby a CdS NW, we show that the wavelength and relative
      intensity of the resonance modes in the NW cavity can systematically be tuned by
      adjusting the relative position of the Ag NP. We further demonstrate that a 56%
      enhancement of Q-factor and an equivalent pi-phase shift of the resonance modes
      can be achieved when the Ag NP is located near the NW end. This hybrid cavity has
      potential applications in active plasmonic and photonic nanodevices.

PMID- 21894937
TI  - Triplet-sensitized photoreactivity of a geminal diazidoalkane.
AB  - Photolysis of 1 in chloroform yielded 2 as the major product and a small quantity
      of 3. Laser flash photolysis demonstrated that upon irradiation, the first
      excited triplet state of the ketone (T(1K)) of 1 is formed and decayed to form
      radical 4, which has a lambda(max) at 380 nm (tau = 2 MUs). Radical 4 expelled a
      nitrogen molecule to yield imine radical 5 (lambda(max) at 300 nm). Density
      functional theory (DFT) calculations showed that the transition state barrier for
      the formation of 5 is approximately 4 kcal/mol. In comparison, photolysis of 1 in
      argon matrices resulted in triplet nitrene 6, which was further characterized
      with (15)N and D isotope labeling and DFT calculations. Prolonged irradiation of
      6 yields triplet imine nitrene 7.

PMID- 21894938
TI  - Highly efficient coupling of photons from nanoemitters into single-mode optical
      fibers.
AB  - Highly efficient coupling of photons from nanoemitters into single-mode optical
      fibers is demonstrated using tapered fibers. A percentage (7.4 +/- 1.2%) of the
      total emitted photons from single CdSe/ZnS nanocrystals were coupled into a 300
      nm diameter tapered fiber. The dependence of the coupling efficiency on the taper
      diameter was investigated and the coupling efficiency was found to increase
      exponentially with decreasing diameter. This method is very promising for
      nanoparticle sensing and single-photon sources.

PMID- 21894940
TI  - High current density Esaki tunnel diodes based on GaSb-InAsSb heterostructure
      nanowires.
AB  - We present electrical characterization of broken gap GaSb-InAsSb nanowire
      heterojunctions. Esaki diode characteristics with maximum reverse current of 1750
      kA/cm(2) at 0.50 V, maximum peak current of 67 kA/cm(2) at 0.11 V, and peak-to
      valley ratio (PVR) of 2.1 are obtained at room temperature. The reverse current
      density is comparable to that of state-of-the-art tunnel diodes based on heavily
      doped p-n junctions. However, the GaSb-InAsSb diodes investigated in this work do
      not rely on heavy doping, which permits studies of transport mechanisms in simple
      transistor structures processed with high-kappa gate dielectrics and top-gates.
      Such processing results in devices with improved PVR (3.5) and stability of the
      electrical properties.

PMID- 21894939
TI  - The physical basis of FGFR3 response to fgf1 and fgf2.
AB  - Fibroblast growth factors (fgfs) play important roles in embryonic development
      and in adult life by controlling cell proliferation, differentiation, and
      migration. There are 18 known fgfs which activate four fibroblast growth factor
      receptors (FGFRs), with different isoforms due to alternative splicing. The
      physical basis behind the specificity of the biological responses mediated by
      different fgf-FGFR pairs is currently unknown. To gain insight into the
      specificity of FGFR3c, a membrane receptor which is critical for bone
      development, we studied, analyzed, and compared the activation of FGFR3c over a
      wide range of fgf1 and fgf2 concentrations. We found that while the strength of
      fgf2 binding to FGFR3c is lower than the strength of fgf1 binding, the fgf2-bound
      dimers exhibit higher phosphorylation of the critical tyrosines in the activation
      loop. As a result, fgf1 and fgf2 elicit a similar FGFR3c response at low, but not
      at high, concentrations. The results demonstrate the versatility of FGFR3c
      response to fgf1 and fgf2 and highlight the complexity in fgf signaling.

PMID- 21894941
TI  - Working together: the combined application of a magnetic field and penetratin for
      the delivery of magnetic nanoparticles to cells in 3D.
AB  - Nanoparticles (NPs) are currently being developed as vehicles for in vivo drug
      delivery. Two of the biggest barriers facing this therapy are the site-specific
      targeting and consequent cellular uptake of drug-loaded NPs(1). In vitro studies
      in 2D cell cultures have shown that an external magnetic field (MF) and
      functionalization with cell-penetrating peptides (CPPs) have the capacity to
      overcome these barriers. This study aimed to investigate if the potential of
      these techniques, which has been reported in 2D, can be successfully applied to
      cells growing in a 3D environment. As such, this study provides a more realistic
      assessment of how these techniques might perform in future clinical settings. The
      effect of a MF and/or penetratin attachment on the uptake of 100 and 200 nm
      fluorescent iron oxide magnetic NPs (mNPs) into a fibroblast-seeded 3D collagen
      gel was quantified by inductively coupled plasma mass spectrometry. The most
      suitable mNP species was further investigated by fluorescence microscopy,
      histology, confocal microscopy, and TEM. Results show that gel mNP uptake
      occurred on average twice as fast in the presence of a MF and up to three times
      faster with penetratin attachment. In addition, a MF increased the distance of
      mNP travel through the gel, while penetratin increased mNP cell localization.
      This work is one of the first to demonstrate that MFs and CPPs can be effectively
      translated for use in 3D systems and, if applied together, will make excellent
      partners to achieve therapeutic drug delivery in vivo.

PMID- 21894942
TI  - Effect of calcium on the morphology and functionality of whey protein
      nanofibrils.
AB  - Self-assembly of amyloid-like nanofibrils during heating of bovine whey proteins
      at 80  degrees C and pH 2 is accelerated by the presence of NaCl and/or CaCl(2),
      but the rheological consequences of accelerated self-assembly are largely
      unknown. This investigation focused on the impact of CaCl(2) on the evolution of
      rheological properties and fibril morphology of heated whey protein isolate
      (WPI), both during self-assembly at high temperature and after cooling.
      Continuous rotational rheometry of heated 2% w/w WPI showed a nonlinear effect of
      CaCl(2) on the viscosity of fibril dispersions, which we attributed to effects on
      fibril flexibility and thus the balance between intrafibril and interfibril
      entanglements. Small-amplitude oscillatory measurements made in situ during
      heating of 10% w/w WPI at 80  degrees C suggest that CaCl(2) is not involved in
      either fibril structure or gel structure, and this was confirmed with dialysis
      experiments.

PMID- 21894943
TI  - Molecular-crowding-induced clustering of DNA-wrapped carbon nanotubes for facile
      length fractionation.
AB  - Emerging applications require single-wall carbon nanotubes (SWCNTs) of well
      defined length. Yet the use of length-defined SWCNTs is limited, in part due to
      the lack of an easily accessible materials preparation method. Here, we present a
      new strategy for SWCNT length fractionation based on molecular crowding induced
      cluster formation. We show that the addition of polyethylene glycol (PEG) as a
      crowding agent into DNA-wrapped SWCNT dispersion leads to the formation of
      reversible, nematic, and rodlike microclusters, which can be collected by gentle
      centrifugation. Since shorter SWCNTs form clusters at higher polyethylene glycol
      concentration, gradual increase in PEG concentration results in length
      fractionated SWCNTs. Using atomic force microscopy (AFM) we show that fractions
      with average lengths of 60-500 nm and standard deviations of 30-40% can be
      obtained. The concept of molecular-crowding-based fractionation should be
      applicable to other nanoparticle dispersions.

PMID- 21894944
TI  - Monitoring of galvanic replacement reaction between silver nanowires and HAuCl4
      by in situ transmission X-ray microscopy.
AB  - Galvanic replacement reaction between silver nanowires and an aqueous solution of
      HAuCl(4) has been successfully monitored in real time by using in situ
      transmission X-ray microscopy (TXM) in combination with a flow cell reactor. The
      in situ observations clearly show the morphological evolution of the solid silver
      nanowires to hollow gold nanotubes in the course of the reaction. Careful
      analysis of the images reveals that the galvanic replacement reaction on the
      silver nanowires involves multiple steps: (i) local initiation of pitting
      process; (ii) anisotropic etching of the silver nanowires and uniform deposition
      of the resulting gold atoms on the surfaces of the nanowires; and (iii)
      reconstruction of the nanotube walls via an Ostwald ripening process. The in situ
      TXM represents a promising approach for studying dynamic processes involved in
      the growth and chemical transformation of nanomaterials in solutions, in
      particular for nanostructures with dimensions larger than 50 nm.

PMID- 21894946
TI  - Responsive two-photon induced europium emission as fluorescent indicator for
      paralytic shellfish saxitoxin.
AB  - A water-soluble europium(III) complex (1) has been synthesized and demonstrated
      to be a specific fluorescence probe for the paralytic shellfish toxin saxitoxin,
      a neurotoxin that blocks the voltage-gated sodium channels on cell membranes.
      Saxitoxin binds to the europium complex (K(B) = 6.1 * 10(4) M(-1)) and triggers a
      two-photon induced f-f emission enhancement by over 100% and increases the two
      photon absorption cross-section from 9 to 36 GM.

PMID- 21894947
TI  - Screw dislocation-driven growth of two-dimensional nanoplates.
AB  - We report the dislocation-driven growth of two-dimensional (2D) nanoplates. They
      are another type of dislocation-driven nanostructure and could find application
      in energy storage, catalysis, and nanoelectronics. We first focus on nanoplates
      of zinc hydroxy sulfate (3Zn(OH)(2).ZnSO(4).0.5H(2)O) synthesized from aqueous
      solutions. Both powder X-ray and electron diffraction confirm the zinc hydroxy
      sulfate (ZHS) crystal structure as well as their conversion to zinc oxide (ZnO).
      Scanning electron, atomic force, and transmission electron microscopy reveal the
      presence of screw dislocations in the ZHS nanoplates. We further demonstrate the
      generality of this mechanism through the growth of 2D nanoplates of alpha
      Co(OH)(2), Ni(OH)(2), and gold that can also follow the dislocation-driven growth
      mechanism. Finally, we propose a unified scheme general to any crystalline
      material that explains the growth of nanoplates as well as different dislocation
      driven nanomaterial morphologies previously observed through consideration of the
      relative crystal growth step velocities at the dislocation core versus the outer
      edges of the growth spiral under various supersaturations.

PMID- 21894948
TI  - Photomodulated rayleigh scattering of single semiconductor nanowires: probing
      electronic band structure.
AB  - The internal electronic structures of single semiconductor nanowires can be
      resolved using photomodulated Rayleigh scattering spectroscopy. The Rayleigh
      scattering from semiconductor nanowires is strongly polarization sensitive which
      allows a nearly background-free method for detecting only the light that is
      scattered from a single nanowire. While the Rayleigh scattering efficiency from a
      semiconductor nanowire depends on the dielectric contrast, it is relatively
      featureless as a function of energy. However, if the nanowire is photomodulated
      using a second pump laser beam, the internal electronic structure can be resolved
      with extremely high signal-to-noise and spectral resolution. The photomodulated
      Rayleigh scattering spectra can be understood theoretically as a first derivative
      of the scattering efficiency that results from a modulation of the band gap and
      depends sensitively on the nanowire diameter. Fits to spectral lineshapes provide
      both the band structure and the diameter of individual GaAs and InP nanowires
      under investigation.

PMID- 21894949
TI  - Far-field optical imaging of a linear array of coupled gold nanocubes: direct
      visualization of dark plasmon propagating modes.
AB  - Plasmonic nanoantenna arrays hold great promise for diffraction-unlimited light
      localization, confinement, and transport. Here, we report on linear plasmonic
      nanoantenna arrays composed of colloidal gold nanocubes precisely assembled using
      a nanomanipulation technique. In particular, we show the direct evidence of dark
      propagating modes in the plasmon coupling regime, allowing for transport of
      guided plasmon waves without far-field radiation losses. Additionally, we
      demonstrate the possibility of plasmon dispersion engineering in coupled gold
      nanocube chains. By assembling a nanocube chain with two sections of coupled
      nanocubes of different intercube separations, we are able to produce the effect
      of a band-pass nanofilter.

PMID- 21894950
TI  - Photoluminescence from inner walls in double-walled carbon nanotubes: some do,
      some do not.
AB  - Double-walled carbon nanotubes (DWNTs) have recently been recognized as important
      members in the carbon nanotube family because they are expected to have certain
      unique properties. For example, DWNTs are expected to replace single-walled
      carbon nanotubes (SWNTs) in biomarker applications and optoelectronics if the
      observed luminescence from DWNTs can be verified. However, due to unavoidable
      byproducts, such as SWNTs, optical properties of DWNTs still remain
      controversial. There is an ongoing debate concerning the ability of DWNTs to
      exhibit photoluminescence (PL). In this report, we aim to clearly resolve this
      debate through the study of carefully separated DWNTs. DWNTs were successfully
      separated from SWNTs using density gradient ultracentrifugation. Here we clearly
      show that light is emitted from the inner wall of DWNTs; however, the intensity
      of the emission is significantly quenched. Interestingly, it was found that a
      very narrow range of diameters of the inner walls of DWNTs is required for PL to
      be observable. All other diameters led to complete PL quenching in DWNTs. In
      short, we have shown that both sides of the debate are correct under certain
      situations. The real answer to the question is that some DWNTs do emit light but
      most DWNTs do not.

PMID- 21894951
TI  - Ultrasound-induced emission enhancement based on structure-dependent homo- and
      heterochiral aggregations of chiral binuclear platinum complexes.
AB  - Instant and precise control of phosphorescent emission can be performed by
      ultrasound-induced gelation of organic liquids with chiral, clothespin-shaped
      trans-bis(salicylaldiminato)Pt(II) complexes, anti-1. Nonemissive solutions of
      racemic, short-linked anti-1a (n = 5) and optically pure, long-linked anti-1c (n
      = 7) in organic liquids are transformed immediately into stable phosphorescent
      gels upon brief irradiation of low-power ultrasound. Emission from the gels can
      be controlled by sonication time, linker length, and optical activity of the
      complexes. Several experimental results indicated that structure-dependent homo-
      and heterochiral aggregations and ultrasound-control of the aggregate morphology
      are key factors for emission enhancement.

PMID- 21894952
TI  - Concise, stereocontrolled synthesis of the citrinadin B core architecture.
AB  - A concise, stereocontrolled synthesis of the citrinadin B core architecture from
      scalemic, readily available starting materials is disclosed. Highlights include
      ready access to both cyclic tryptophan tautomer and trans-2,6-disubstituted
      piperidine fragments, an efficient, stereoretentive mixed Claisen acylation for
      the coupling of these halves, and further diastereoselective carbonyl addition
      and oxidative rearrangement for assembly of the core.

PMID- 21894954
TI  - Cyanocuprates convert carboxylic acids directly into ketones.
AB  - Carboxylic acids were converted directly in 56-99% yields into methyl, n-butyl,
      and isopropyl ketones using excess cyanocuprates R(2)CuLi.LiCN. A substrate with
      a stereocenter alpha to the carboxylic acid was converted into ketones with very
      little loss of enantiomeric purity. A variety of functional groups were tolerated
      including aryl bromides. This direct transformation of a carboxylic acid into
      ketone with minimal tertiary alcohol formation is proposed to involve a
      relatively stable copper ketal tetrahedral intermediate.

PMID- 21894953
TI  - Rhodium-catalyzed cross-coupling reaction of arylboronates and diazoesters and
      tandem alkylation reaction for the synthesis of quaternary alpha,alpha
      heterodiaryl carboxylic esters.
AB  - A rhodium-catalyzed one-pot three-component coupling reaction was developed for
      the synthesis of quaternary alpha,alpha-heterodiaryl carboxylic esters. This
      reaction involves cross-coupling of the arylrhodium(I) complexes with alpha
      aryldiazoacetates to form oxa-pi-allylrhodium complexes. With KOtBu and alkyl
      halides, tandem alkylation of the allyl complex occurs to form a quaternary
      stereocenter at the carbenic carbon.

PMID- 21894955
TI  - Intraparticle charge delocalization of carbene-functionalized ruthenium
      nanoparticles manipulated by selective ion binding.
AB  - Olefin metathesis reactions of carbene-stabilized ruthenium nanoparticles were
      exploited for the incorporation of multiple functional moieties onto the
      nanoparticle surface. When the nanoparticles were cofunctionalized with 4
      vinylbenzo-18-crown-6 and 1-vinylpyrene, the resulting particles exhibited
      fluorescence characteristics that were consistent with dimeric pyrene with a
      conjugated chemical bridge, with three peaks observed in the emission spectra at
      391, 410, and 485 nm. The behaviors were ascribed to intraparticle charge
      delocalization between the pyrene moieties afforded by the conjugated Ru?carbene
      interfacial linkages. Notably, upon the binding of metal ions in the crown ether
      cavity, the emission intensity of the nanoparticle fluorescence was found to
      diminish at 485 nm and concurrently increase at 391 and 410 nm rather markedly,
      with the most significant effects observed with K(+). This was accounted for by
      the selective binding of 18-crown-6 to potassium ions, where the positively
      charged ions led to the polarization of the nanoparticle core electrons that was
      facililated by the conjugated linkage to the metal surface and hence impeded
      intraparticle charge delocalization. Control experiments with a pyrene-crown
      ether conjugate (2) and with ruthenium nanoparticles cofunctionalized with 4
      vinylbenzo-18-crown-6 and 1-allylpyrene suggested that the through-bond pathway
      played a predominant role in the manipulation of intraparticle electronic
      communication whereas the contributions from simple electrostatic interactions
      (i.e., through-space pathway) were minimal.

PMID- 21894956
TI  - Simultaneous determination of free amino acid content in tea infusions by using
      high-performance liquid chromatography with fluorescence detection coupled with
      alternating penalty trilinear decomposition algorithm.
AB  - In this paper, a novel application of alternating penalty trilinear decomposition
      (APTLD) for high-performance liquid chromatography with fluorescence detection
      (HPLC-FLD) has been developed to simultaneously determine the contents of free
      amino acids in tea. Although the spectra of amino acid derivatives were similar
      and a large number of water-soluble compounds are coextracted, APTLD could
      predict the accurate concentrations together with reasonable resolution of
      chromatographic and spectral profiles for the amino acids of interest owing to
      its "second-order advantage". An additional advantage of the proposed method is
      lower cost than traditional methods. The results indicate that it is an
      attractive alternative strategy for the routine resolution and quantification of
      amino acids in the presence of unknown interferences or when complete separation
      is not easily achieved.

PMID- 21894957
TI  - Enzymatic and chemical treatment limits on the controlled solubilization of
      brewers' spent grain.
AB  - The enzymatic hydrolysis of brewers' spent grain (BSG) has been investigated
      through treatment with commercial carbohydrases and proteases. Resultant residues
      were then chemically fractionated and delignified. Enzymatic treatments released
      25-30% of the BSG mass and yielded precursors suitable for subsequent conversion
      to potentially value-added products. Controlled chemical fractionation
      selectively solubilized arabinoxylan but with no differences apparent due to
      prior enzyme treatment. The loss of non-polysaccharide components during alkali
      treatment suggests the presence of a high proportion of alkali-soluble lignin.
      Further delignification of the alkali-insoluble residues and further chemical
      fractionation released the remaining hemicellulose, to yield a residue which was
      >90% cellulose. Further knowledge of the properties and interaction between BSG
      polymers will facilitate an improved enzyme-assisted total deconstruction of BSG
      and hence the exploitation of its biomass.

PMID- 21894958
TI  - Characteristics of pregelatinized ae mutant rice flours prepared by boiling after
      preroasting.
AB  - As ae mutant rice, such as EM10, lacks the starch branching enzyme IIb, its
      amylopectin contains more long-chain glucans than that of ordinary Indica and
      Japonica rice grains. Although boiled grains of ae rice cultivars are too hard
      and nonsticky for table rice, they are promising in terms of biofunctionality,
      such as prevention of diabetes. The present paper investigates the
      characterization of a novel group of four ae mutant rice cultivars (EM72, EM145,
      EM174, and EM189). They were subjected to the evaluation for their main chemical
      components, physical properties, and enzyme activities at different grain
      conditions (raw milled rice, roasted rice, boiled rice, and rice boiled after
      preroasting). These mutant rice grains are characterized by high apparent
      amylose, high protein and high glucose contents, high pasting temperature, high
      alpha-amylase activities, high resistant starch, and low degree of
      gelatinization. A novel method was developed to maintain the high resistant
      starch contents of gelatinized rice grains. Rice boild after preroasting showed a
      higher ratio of resistant starch and a lower amount of glucose than ordinary
      boiled rice. It became possible to produce high-quality and biofunctional
      pregelatinized rice flours by boiling with frozen fruits, such as tomatoes, after
      rice grains had been preroasted. These ae mutants were found to be suitable
      materials for rice/fruit or rice/vegetable products to serve as palatable, low
      glucose, and high resistant starch rice products.

PMID- 21894959
TI  - Design, synthesis, crystal structure analysis, and insecticidal evaluation of
      phenylazoneonicotinoids.
AB  - On the basis of research of the proposed modes of action between neonicotinoids
      and insect nicotinic acetylcholine receptor (nAChR), a series of
      phenylazoneonicotinoids were designed and synthesized to further promote the pi
      pi interaction between molecule and amino acid residues. The target compounds
      have been identified on the basis of satisfactory analytical and spectral ((1)H
      NMR, (13)C NMR, HRMS, and X-ray) data. The preliminary results revealed that tiny
      differences in substitutes resulted in different configurations and great
      bioactivity variations. Some compounds with electron-donating groups on positions
      2 and 6 of the phenyl ring presented higher insecticidal activity than
      imidacloprid against cowpea aphids ( Aphis craccivora ). The impressive crystal
      structure of the excellent insecticidal activity compound 9q clearly proved that
      the functional electronegative pharmacophore was approximately vertical to the
      methyleneimidazolidine plane. The differences in the mode of interaction on nAChR
      of typical compounds 9h and 9q remain unclear.

PMID- 21894960
TI  - Palladium-catalyzed carbohalogenation: bromide to iodide exchange and domino
      processes.
AB  - Aryl bromides have been used to prepare a variety of nitrogen- and oxygen
      containing heterocycles featuring new carbon-carbon and carbon-iodine bonds. This
      palladium-catalyzed carbohalogenation requires potassium iodide for the reaction
      to proceed in high yields. Additionally, the first examples of domino
      carbohalogenation reactions have been demonstrated using both aryl iodide and
      aryl bromide starting materials. Complex products with multiple rings and
      stereogenic centers are generated in excellent yields with moderate to excellent
      diastereoselectivities.

PMID- 21894961
TI  - Electrocatalytic water oxidation beginning with the cobalt polyoxometalate
      [Co4(H2O)2(PW9O34)2]10-: identification of heterogeneous CoOx as the dominant
      catalyst.
AB  - The question of "what is the true catalyst?" when beginning with the cobalt
      polyoxometalate (POM) [Co(4)(H(2)O)(2)(PW(9)O(34))(2)](10-) in electrochemical
      water oxidation catalysis is examined in pH 8.0 sodium phosphate buffer at a
      glassy carbon electrode. Is [Co(4)(H(2)O)(2)(PW(9)O(34))(2)](10-) a true water
      oxidation catalyst (WOC), or just a precatalyst? Electrochemical, kinetic, UV
      vis, SEM, EDX, and other data provide four main lines of compelling evidence
      that, under the conditions used herein, the dominant WOC is actually
      heterogeneous CoO(x) and not homogeneous [Co(4)(H(2)O)(2)(PW(9)O(34))(2)](10-).

PMID- 21894962
TI  - Mapping the landscape of RNA dynamics with NMR spectroscopy.
AB  - Among the three major classes of biomacromolecules (DNA, RNA, and proteins) RNA's
      pronounced dynamics are the most explicitly linked to its wide variety of
      functions, which include catalysis and the regulation of transcription,
      translation, and splicing. These functions are mediated by a range of RNA
      biomachinery, including such varied examples as macromolecular noncoding RNAs,
      microRNAs, small interfering RNAs, riboswitch RNAs, and RNA thermometers. In each
      case, the functional dynamics of an interconversion is characterized by an
      associated rate constant. In this Account, we provide an introduction to NMR
      spectroscopic characterization of the landscape of RNA dynamics. We introduce
      strategies for measuring NMR parameters at various time scales as well as the
      underlying models for describing the corresponding rate constants.  RNA exhibits
      significant dynamic motion, which can be modulated by (i) intermolecular
      interactions, including specific and nonspecific binding of ions (such as Mg(2+)
      and tertiary amines), (ii) metabolites in riboswitches or RNA aptamers, and (iii)
      macromolecular interactions within ribonucleic protein particles, including the
      ribosome and the spliceosome. Our understanding of the nature of these dynamic
      changes in RNA targets is now being incorporated into RNA-specific approaches in
      the design of RNA inhibitors. Interactions of RNA with proteins, other RNAs, or
      small molecules often occur through binding mechanisms that follow an induced fit
      mechanism or a conformational selection mechanism, in which one of several
      populated RNA conformations is selected through ligand binding.  The extent of
      functional dynamics, including the kinetic formation of a specific RNA tertiary
      fold, is dependent on the messenger RNA (mRNA) chain length. Thus, during de novo
      synthesis of mRNA, both in prokaryotes and eukaryotes, nascent mRNA of various
      lengths will adopt different secondary and tertiary structures. The speed of
      transcription has a critical influence on the functional dynamics of the RNA
      being synthesized.  In addition to modulating the local dynamics of a
      conformational RNA ensemble, a given RNA sequence may adopt more than one global,
      three-dimensional structure. RNA modification is one way to select among these
      alternative structures, which are often characterized by nearly equal stability,
      but with high energy barriers for conformational interconversion. The refolding
      of different secondary and tertiary structures has been found to be a major
      regulatory mechanism for transcription and translation. These conformational
      transitions can be characterized with NMR spectroscopy, for any given RNA
      sequence, in response to external stimuli.

PMID- 21894963
TI  - Importance of out-of-state spin-orbit coupling for slow magnetic relaxation in
      mononuclear Fe(II) complexes.
AB  - Two mononuclear high-spin Fe(II) complexes with trigonal planar
      ([Fe(II)(N(TMS)(2))(2)(PCy(3))] (1) and distorted tetrahedral
      ([Fe(II)(N(TMS)(2))(2)(depe)] (2) geometries are reported (TMS = SiMe(3), Cy =
      cyclohexyl, depe = 1,2-bis(diethylphosphino)ethane). The magnetic properties of 1
      and 2 reveal the profound effect of out-of-state spin-orbit coupling (SOC) on
      slow magnetic relaxation. Complex 1 exhibits slow relaxation of the magnetization
      under an applied optimal dc field of 600 Oe due to the presence of low-lying
      electronic excited states that mix with the ground electronic state. This mixing
      re-introduces orbital angular momentum into the electronic ground state via SOC,
      and 1 thus behaves as a field-induced single-molecule magnet. In complex 2, the
      lowest-energy excited states have higher energy due to the ligand field of the
      distorted tetrahedral geometry. This higher energy gap minimizes out-of-state SOC
      mixing and zero-field splitting, thus precluding slow relaxation of the
      magnetization for 2.

PMID- 21894964
TI  - Method for simultaneous imaging of endogenous low molecular weight metabolites in
      mouse brain using TiO2 nanoparticles in nanoparticle-assisted laser
      desorption/ionization-imaging mass spectrometry.
AB  - We report the detection of a group of endogenous low molecular weight metabolites
      (LMWM) in mouse brain (80-500 Da) using TiO(2) nanoparticles (NPs) in
      nanoparticle-assisted laser desorption/ionization-imaging mass spectrometry (Nano
      PALDI-IMS) without any washing and separation step prior to MS analysis. The
      identification of metabolites using TiO(2) NPs was compared with a conventional
      organic matrix 2,5-dihydroxybenzoic acid (DHB) where signals of 179 molecules
      were specific to TiO(2) NPs, 4 were specific to DHB, and 21 were common to both
      TiO(2) NPs and DHB. The use of TiO(2) NPs enabled the detection of a higher
      number of LMWM as compared to DHB and gold NPs as a matrix. This approach is a
      simple, inexpensive, washing, and separation free for imaging and identification
      of LMWM in mouse brain. We believe that the biochemical information from distinct
      regions of the brain using a Nano-PALDI-IMS will be helpful in elucidating the
      imbalances linked with diseases in biomedical samples.

PMID- 21894965
TI  - Transfer of CVD-grown monolayer graphene onto arbitrary substrates.
AB  - Reproducible dry and wet transfer techniques were developed to improve the
      transfer of large-area monolayer graphene grown on copper foils by chemical vapor
      deposition (CVD). The techniques reported here allow transfer onto three
      different classes of substrates: substrates covered with shallow depressions,
      perforated substrates, and flat substrates. A novel dry transfer technique was
      used to make graphene-sealed microchambers without trapping liquid inside. The
      dry transfer technique utilizes a polydimethylsiloxane frame that attaches to the
      poly(methyl methacrylate) spun over the graphene film, and the monolayer graphene
      was transferred onto shallow depressions with 300 nm depth. The improved wet
      transfer onto perforated substrates with 2.7 MUm diameter holes yields 98%
      coverage of holes covered with continuous films, allowing the ready use of Raman
      spectroscopy and transmission electron microscopy to study the intrinsic
      properties of CVD-grown monolayer graphene. Additionally, monolayer graphene
      transferred onto flat substrates has fewer cracks and tears, as well as lower
      sheet resistance than previous transfer techniques. Monolayer graphene films
      transferred onto glass had a sheet resistance of ~980 Omega/sq and a
      transmittance of 97.6%. These transfer techniques open up possibilities for the
      fabrication of various graphene devices with unique configurations and enhanced
      performance.

PMID- 21894966
TI  - Preface: Forum on redox-active ligands.

PMID- 21894967
TI  - White phosphorus activation at a metal-phosphorus triple bond: a new route to
      cyclo-triphosphorus or cyclo-pentaphosphorus complexes of niobium.
AB  - The Nb-P triple bond in [P=Nb(N[Np]Ar)(3)](-) (Np = CH(2)(t)Bu; Ar = 3,5
      Me(2)C(6)H(3)) has produced the first case of P(4) activation by a metal-ligand
      multiple bond. Treatment of P(4) with the sodium salt of the niobium phosphide
      complex in weakly coordinating solvents led to formation of the cyclo-P(3) anion
      [(P(3))Nb(N[Np]Ar)(3)](-). Treatment in tetrahydrofuran (THF) led to the
      formation of a cyclo-P(5) anion [(Ar[Np]N)(eta(4)-P(5))Nb(N[Np]Ar)(2)](-), which
      represents a rare example of a substituted pentaphosphacyclopentadienyl ligand.
      The P(4) activation pathway was shown to depend on the dimer-monomer equilibrium
      of the niobium phosphide reagent, which, in turn, depends on the solvent used for
      the reaction. The pathway leading to the cyclo-P(3) product was shown to require
      a 2:1 ratio of the phosphide anion to P(4), while the cyclo-P(5) formation
      requires a 1:1 ratio. The cyclo-P(3) salt has been isolated in 56% yield as
      orange crystals of the [Na(THF)](2)[(P(3))Nb(N[Np]Ar)(3)](2) dimer or in 83%
      yield as an orange powder of [Na(12-crown-4)(2)][(P(3))Nb(N[Np]Ar)(3)]. A solid
      state X-ray diffraction experiment on the former salt revealed that each Nb-P(3)
      unit exhibits pseudo-C(3) symmetry, while (31)P NMR spectroscopy showed a sharp
      signal at -223 ppm that splits into a doublet-triplet pair below -50  degrees C.
      It was demonstrated that this salt can serve as a P(3)(3-) source upon treatment
      with AsCl(3), albeit with modest yield of AsP(3). The cyclo-P(5) salt was
      isolated in 71% yield and structurally characterized from red crystals of
      [Na(THF)(6)][(Ar[Np]N)(eta(4)-P(5))Nb(N[Np]Ar)(2)]. The anion in this salt can be
      interpreted as the product of trapping of an intermediate
      pentaphosphacycplopentadienyl structure through migration of one anilide ligand
      onto the P(5) ring. The W(CO)(5)-capped cyclo-P(3) salt was also isolated in 60%
      yield as [Na(THF)][(OC)(5)W(P(3))Nb(N[Np]Ar)(3)] from the activation of 0.5 equiv
      of P(4) with the sodium salt of the tungsten pentacarbonyl adduct of the niobium
      phosphide anion.

PMID- 21894968
TI  - Study of molybdenum(4+) quinoxalyldithiolenes as models for the noninnocent
      pyranopterin in the molybdenum cofactor.
AB  - A model system for the molybdenum cofactor has been developed that illustrates
      the noninnocent behavior of an N-heterocycle appended to a dithiolene chelate on
      molybdenum. The pyranopterin of the molybdenum cofactor is modeled by a
      quinoxalyldithiolene ligand (S(2)BMOQO) formed from the reaction of molybdenum
      tetrasulfide and quinoxalylalkyne. The resulting complexes TEA[Tp*MoX(S(2)BMOQO)]
      [1, X = S; 3, X = O; TEA = tetraethylammonium; Tp* = hydrotris(3,5
      dimethylpyrazolyl)borate] undergo a dehydration-driven intramolecular cyclization
      within quinoxalyldithiolene, forming Tp*MoX(pyrrolo-S(2)BMOQO) (2, X = S; 4, X =
      O). 4 can be oxidized by one electron to produce the molybdenum(5+) complex 5. In
      a preliminary report of this work, evidence from X-ray crystallography,
      electronic absorption and resonance Raman spectroscopies, and density functional
      theory (DFT) bonding calculations revealed that 4 possesses an unusual asymmetric
      dithiolene chelate with significant thione-thiolate character. The results
      described here provide a detailed description of the reaction conditions that
      lead to the formation of 4. Data from cyclic voltammetry, additional DFT
      calculations, and several spectroscopic methods (IR, electronic absorption,
      resonance Raman, and electron paramagnetic resonance) have been used to
      characterize the properties of members in this suite of five Mo(S(2)BMOQO)
      complexes and further substantiate the highly electron-withdrawing character of
      the pyrrolo-S(2)BMOQO ligand in 2, 4, and 5. This study of the unique noninnocent
      ligand S(2)BMOQO provides examples of the roles that the N-heterocycle pterin can
      play as an essential part of the molybdenum cofactor. The versatile nature of a
      dithiolene appended by heterocycles may aid in modulating the redox processes of
      the molybdenum center during the course of enzyme catalysis.

PMID- 21894969
TI  - Temperature dependence of the fluorescence properties of curcumin.
AB  - Steady-state and time-resolved techniques were employed to study the nonradiative
      process of curcumin dissolved in ethanol and 1-propanol in a wide range of
      temperatures. We found that the nonradiative rate constants at temperatures
      between 175-250 K qualitatively follow the same trend as the dielectric
      relaxation times of both neat solvents. We attribute the nonradiative process to
      solvent-controlled proton transfer. We also found a kinetic isotope effect on the
      nonradiative process rate constant of ~2. We propose a model in which the excited
      state proton transfer breaks the planar hexagonal structure of the keto-enol
      center of the molecule. This, in turn, enhances the nonradiative process driven
      by the twist angle between the two phenol moieties.

PMID- 21894970
TI  - Enhanced visible-light activity of titania via confinement inside carbon
      nanotubes.
AB  - Titania confined inside carbon nanotubes (CNTs) was synthesized using a
      restrained hydrolysis method. Raman spectra and magnetic measurements using a
      SQUID magnetometer suggested the formation of remarkable oxygen vacancies over
      the encapsulated TiO(2) in comparison with nanoparticles dispersed on the outer
      surface of CNTs, extending the photoresponse of TiO(2) from the UV to the visible
      light region. The CNT-confined TiO(2) exhibited improved visible-light activity
      in the degradation of methylene blue (MB) relative to the outside titania and
      commercial P25, which is attributed to the modification of the electronic
      structure of TiO(2) induced by the unique confinement inside CNTs. These results
      provide further insight into the effect of confinement within CNTs, and the
      composites are expected to be promising for applications in visible-light
      photocatalysis.

PMID- 21894971
TI  - Conversion reaction mechanisms in lithium ion batteries: study of the binary
      metal fluoride electrodes.
AB  - Materials that undergo a conversion reaction with lithium (e.g., metal fluorides
      MF(2): M = Fe, Cu, ...) often accommodate more than one Li atom per transition
      metal cation, and are promising candidates for high-capacity cathodes for lithium
      ion batteries. However, little is known about the mechanisms involved in the
      conversion process, the origins of the large polarization during electrochemical
      cycling, and why some materials are reversible (e.g., FeF(2)) while others are
      not (e.g., CuF(2)). In this study, we investigated the conversion reaction of
      binary metal fluorides, FeF(2) and CuF(2), using a series of local and bulk
      probes to better understand the mechanisms underlying their contrasting
      electrochemical behavior. X-ray pair-distribution-function and magnetization
      measurements were used to determine changes in short-range ordering, particle
      size and microstructure, while high-resolution transmission electron microscopy
      (TEM) and electron energy-loss spectroscopy (EELS) were used to measure the
      atomic-level structure of individual particles and map the phase distribution in
      the initial and fully lithiated electrodes. Both FeF(2) and CuF(2) react with
      lithium via a direct conversion process with no intercalation step, but there are
      differences in the conversion process and final phase distribution. During the
      reaction of Li(+) with FeF(2), small metallic iron nanoparticles (<5 nm in
      diameter) nucleate in close proximity to the converted LiF phase, as a result of
      the low diffusivity of iron. The iron nanoparticles are interconnected and form a
      bicontinuous network, which provides a pathway for local electron transport
      through the insulating LiF phase. In addition, the massive interface formed
      between nanoscale solid phases provides a pathway for ionic transport during the
      conversion process. These results offer the first experimental evidence
      explaining the origins of the high lithium reversibility in FeF(2). In contrast
      to FeF(2), no continuous Cu network was observed in the lithiated CuF(2); rather,
      the converted Cu segregates to large particles (5-12 nm in diameter) during the
      first discharge, which may be partially responsible for the lack of reversibility
      in the CuF(2) electrode.

PMID- 21894972
TI  - Multicomponent click synthesis of 1,2,3-triazoles from epoxides in water
      catalyzed by copper nanoparticles on activated carbon.
AB  - Copper nanoparticles on activated carbon have been found to effectively catalyze
      the multicomponent synthesis of beta-hydroxy-1,2,3-triazoles from a variety of
      epoxides and alkynes in water. The catalyst is easy to prepare, reusable at a low
      copper loading (0.5 mol %), and exhibits higher catalytic activity than some
      commercially available copper sources. The regio- and stereochemistry of the
      reaction has been revised and unequivocally established on the basis of X-ray
      crystallographic analyses. An NMR experiment has been implemented for the rapid
      and unmistakable determination of the regiochemistry of the process. Some
      mechanistic aspects of the reaction have been also undertaken which unveil the
      participation of copper(I) acetylides.

PMID- 21894973
TI  - Asymmetric Michael addition of malonates to enones catalyzed by a primary beta
      amino acid and its lithium salt.
AB  - Highly enantioselective Michael addition of malonates to enones was achieved
      using a mixed catalyst consisting of a primary beta-amino acid, O-TBDPS (S)-beta
      homoserine, and its lithium salt. Various cyclic and acyclic enones were
      converted into 1,5-ketoesters in high yields (up to 92%) with high
      enantioselectivity (up to 97% ee) under mild reaction conditions. Details of
      synthesis of the catalyst, optimization of the reaction conditions for the
      Michael addition reaction, and a plausible reaction mechanism are described.

PMID- 21894974
TI  - Understanding three hydration-dependent transitions of zwitterionic
      carboxybetaine hydrogel by molecular dynamics simulations.
AB  - In this work, molecular dynamics simulations were performed to study a
      carboxybetaine methacrylate (CBMA) hydrogel under various swelling states. The
      water content in this study ranged from 28% to 91% of the total weight of the
      hydrogel. Three transitions of the CBMA hydrogel were observed as the water
      content increased. The first transition occurs when the water content increases
      from 33% to 37%. The observed kink in the self-diffusion coefficient of water
      indicates that the hydration of the polymer network of the hydrogel is saturated;
      the further added water is in a less confined state. The second transition was
      found to be related to the physical cross-links of the polymer network. As the
      water content rises to above 62%, the lifetime of the physical cross-links
      decreases significantly. This abrupt change in the lifetime indicates that the
      transition represents the equilibrium swelling state of the hydrogel. Finally,
      the third transition was observed when the water content goes above 81%. The
      significant increases in the bond and angle energies of the polymer network
      indicate that the hydrogel reaches its upper limit swelling state at this
      transition. These results are comparable to previously published experimental
      studies of similar zwitterionic hydrogels.

PMID- 21894975
TI  - Fingerprints for structural defects in poly(thienylene vinylene) (PTV): a joint
      theoretical-experimental NMR study on model molecules.
AB  - In the field of plastic electronics, low band gap conjugated polymers like
      poly(thienylene vinylene) (PTV) and its derivatives are a promising class of
      materials that can be obtained with high molecular weight via the so-called
      dithiocarbamate precursor route. We have performed a joint experimental
      theoretical study of the full NMR chemical shift assignment in a series of
      thiophene-based model compounds, which aims at (i) benchmarking the quantum
      chemical calculations against experiments, (ii) identifying the signature of
      possible structural defects that can appear during the polymerization of PTV's,
      namely head-to-head and tail-to-tail defects, and (iii) defining a criterion
      regarding regioregularity.

PMID- 21894976
TI  - Studies of histidine as a suitable isoelectric buffer for tryptic digestion and
      isoelectric trapping fractionation followed by capillary electrophoresis-mass
      spectrometry for proteomic analysis.
AB  - The use of histidine as a protein digestion buffer followed by isoelectric
      trapping separations using "membrane separated wells for isoelectric focusing and
      trapping" (MSWIFT) and mass spectrometry (MS) analysis is described. Tryptic
      digestion of bovine serum albumin (BSA) performed in histidine buffered solutions
      yields similar amino acid sequence coverage values to those obtained using
      ammonium bicarbonate buffer. Time course studies suggest that histidine buffers
      provide faster migration of peptides from the loading compartment compared to
      digestions prepared in ammonium bicarbonate due to differences in conductivities
      of the two buffers. In addition, this sample preparation method and MSWIFT
      separations have been coupled with capillary electrophoresis (CE) and matrix
      assisted laser desorption ionization-mass spectrometry (MALDI-MS) as an
      alternative separation approach for proteomic studies. Tryptic peptides of
      ribosomal proteins in histidine are fractionated using MSWIFT followed by CE
      MALDI-MS, which further illustrates the ability to couple fractions from a pI
      based separation device to CE-MS. Specifically, two-dimensional CE-MS plots
      provide a direct correlation between the numbers of basic residues within the
      peptide sequence displayed in charge-state trend lines. Combining MSWIFT and CE
      MS provides added information regarding peptide sequence, specifically pI and in
      solution charge state. Post-translational modifications can also be identified
      using this method.

PMID- 21894977
TI  - Conformation and dynamics of 18-membered hexathiametacyclophanes: a two step
      racemization as studied by deuterium NMR in chiral lyotropic liquid crystals.
AB  - The conformation and interconversion dynamics of two derivatives of the 18
      membered hexathia metacyclophane 1 and 2 were studied by (1)H NMR spectroscopy in
      isotropic solvents and by (2)H NMR in chiral liquid crystalline (CLC) solutions,
      as well as by molecular structure computations. For the analysis of the dynamic
      effects, we made use of the concepts of "average symmetry" and "isodynamic
      groups", introduced by Altmann (Altmann, Proc. R. Soc.1967, 184, A298). Compound
      1, which is unsubstituted in the inner aromatic site, has, according to the NMR
      and molecular force field calculations, a boat shaped ground conformation with
      C(2) symmetry. It is highly flexible and in the NMR spectrum exhibits two
      successive dynamic processes. There is a low temperature (170-210 K, E(a) = 10.5
      kcal/mol) alternate "wing flipping", which corresponds to interchange between
      pairs of enantiomers and results, in the fast exchange limit, in an average
      prochiral molecule with C(2v) symmetry. This process is followed, at higher
      temperatures (290-320 K, E(a) = 28.5 kcal/mol), by an umbrella flipping type
      inversion with an average structure of D(2h) symmetry. This second process
      involves averaging of effective enantiotopic into homotopic sites and can only be
      studied in chiral solvents. The origin of the chiral discrimination and of their
      stepwise averaging is discussed. Compound 2, which is substituted with methoxy
      groups at the inner sites of the benzene rings, is much less flexible and
      exhibits dynamic effects in the NMR spectrum only at temperatures above 370 K. We
      were able to study the kinetic parameters of this process in isotropic solvents
      (E(a) = 21.4 kcal/mol). As for 1, the detailed mechanism of this process can in
      principle be established using dynamic NMR in CLC; however, experimental
      limitation precluded us from doing so. Possible alternatives and their effect on
      the 1D and 2D exchange spectra in CLC are discussed in a concluding section.

PMID- 21894978
TI  - Molecular dynamics study on Au/Fe3O4 nanocomposites and their surface function
      toward amino acids.
AB  - The deposition of gold nanoparticles on the magnetite (Fe(3)O(4)) surface is
      demonstrated through a molecular dynamics method. The simulated results show that
      an intermediate layer composed by such as a surfactant, polymer, or silica plays
      a key role in the formation of core/shell Fe(3)O(4)/Au nanostructures. The
      functional groups of the intermediate layer are crucial factors in depositing
      gold onto the Fe(3)O(4) surface via nonbonding interactions, in which the van der
      Waals and columbic forces will determine the strength of interaction toward the
      gold and iron oxide. Such interactions can affect the stability of the metal
      coated nanocomposites and hence the functional properties. The nanocomposite is
      further investigated on the surface adsorption of amino acids (e.g., cysteine),
      which may be useful for functional exploration in biomedical applications.

PMID- 21894980
TI  - Use of dual polarization interferometry as a diagnostic tool for protein
      crystallization.
AB  - The use of dual polarization interferometry (DPI) as a tool for probing the
      different possible outcomes of protein crystallization experiments is described.
      DPI is a surface analytical technique used for the characterization of structure
      and interactions of molecular layers on an optical waveguide surface for a wide
      range of applications, including protein-protein interactions and conformational
      changes. The application of this technique provides a "signature" of
      crystallization events, thus predicting if there will be protein crystal
      formation, amorphous precipitate, or clear solution. The technique was
      demonstrated on a number of model proteins, and it also produced meaningful
      results in the case of two problematic target proteins. DPI in conjunction with a
      dialysis setup, allows changes in the protein solution above the waveguide
      surface to be monitored simultaneously with continuous control of its precipitant
      content. DPI has the potential to be used as a powerful method for discovering
      crystallization conditions, for obtaining information on the crystallization
      process, and as an aid in crystal optimization. It has also provided what is, to
      the best of our knowledge, the most direct observation to date of salting-in
      behavior in a protein-salt solution.

PMID- 21894979
TI  - Molecular origin of electron paramagnetic resonance line shapes on beta-barrel
      membrane proteins: the local solvation environment modulates spin-label
      configuration.
AB  - In this work, electron paramagnetic resonance (EPR) spectroscopy and X-ray
      crystallography were used to examine the origins of EPR line shapes from spin
      labels at the protein-lipid interface on the beta-barrel membrane protein BtuB.
      Two atomic-resolution structures were obtained for the methanethiosulfonate spin
      label derivatized to cysteines on the membrane-facing surface of BtuB. At one of
      these sites, position 156, the label side chain resides in a pocket formed by
      neighboring residues; however, it extends from the protein surface and yields a
      single-component EPR spectrum in the crystal that results primarily from fast
      rotation about the fourth and fifth bonds linking the spin-label to the protein
      backbone. In lipid bilayers, site 156 yields a multicomponent spectrum resulting
      from different rotameric states of the labeled side chain. Moreover, changes in
      the lipid environment, such as variations in bilayer thickness, modulate the EPR
      spectrum by modulating label rotamer populations. At a second site, position 371,
      the labeled side chain interacts with a pocket on the protein surface, leading to
      a highly immobilized single-component EPR spectrum that is not sensitive to
      hydrocarbon thickness. This spectrum is similar to that seen at other sites that
      are deep in the hydrocarbon, such as position 170. This work indicates that the
      rotameric states of spin-labels on exposed hydrocarbon sites are sensitive to the
      environment at the protein-hydrocarbon interface, and that this environment may
      modulate weak interactions between the labeled side chain and the protein
      surface. In the case of BtuB, lipid acyl chain packing is not symmetric around
      the beta-barrel, and EPR spectra from labeled hydrocarbon-facing sites in BtuB
      may reflect this asymmetry. In addition to facilitating the interpretation of EPR
      spectra of membrane proteins, these results have important implications for the
      use of long-range distance restraints in protein structure refinement that are
      obtained from spin-labels.

PMID- 21894981
TI  - Symmetric pH-dependent swelling and antibacterial properties of chitosan brushes.
AB  - Charged polymer brushes grafted to surfaces are of great interest for
      antibacterial, biosensor, nanofluidic, and drug delivery applications. In this
      paper, chitosans with quaternary ammonium salts, CH-Q, were immobilized on
      silicon oxide and characterized by in situ quartz-crystal microbalance with
      dissipation, QCM-D, and in situ spectroscopic ellipsometry, SE. Both methods
      showed that the hydrated film exhibited a minimum thickness of ~40 nm near pH 5
      that increased strongly (up to ~80 nm) at lower and higher pH. This symmetric
      swelling is surprising because CH-Q is a cationic polymer. The CH-Q grafted layer
      was stable for pH values from 3 to 8 and exhibited rapid, reversible swelling and
      contraction upon varying pH. The CH-Q layer also reduced S. aureus colonization
      by a factor of ~30* compared to bare silicon oxide and an amine terminated silane
      grafted to silicon oxide. This antibacterial characteristic of CH-Q is attributed
      to the quaternary ammonium salts and the flexible polymer brush.

PMID- 21894982
TI  - Improving the yield of mono-DNA-functionalized gold nanoparticles through dual
      steric hindrance.
AB  - A novel strategy of dual steric hindrance, which was obtained by Janus
      modification of gold nanoparticles (Au NPs) and volume exclusion of DNA, was
      adopted to prepare mono-DNA-modified Au NPs. The yield of mono-DNA-functionalized
      Au NPs significantly improved from 44 to 70% in the reaction between Au NPs and
      thiolated DNA. Furthermore, the specificity of mono-DNA-functionalized Au NPs was
      enhanced from 57 to 95%. The as-prepared Au NPs without postsynthetic treatment
      showed good controllability in self-assembly fabrication of complex
      nanostructures.

PMID- 21894983
TI  - Surface rheology of saponin adsorption layers.
AB  - Extracts of the Quillaja saponaria tree contain natural surfactant molecules
      called saponins that very efficiently stabilize foams and emulsions. Therefore,
      such extracts are widely used in several technologies. In addition, saponins have
      demonstrated nontrivial bioactivity and are currently used as essential
      ingredients in vaccines, food supplements, and other health products. Previous
      preliminary studies showed that saponins have some peculiar surface properties,
      such as a very high surface modulus, that may have an important impact on the
      mechanisms of foam and emulsion stabilization. Here we present a detailed
      characterization of the main surface properties of highly purified aqueous
      extracts of Quillaja saponins. Surface tension isotherms showed that the purified
      Quillaja saponins behave as nonionic surfactants with a relatively high cmc
      (0.025 wt %). The saponin adsorption isotherm is described well by the Volmer
      equation, with an area per molecule of close to 1 nm(2). By comparing this area
      to the molecular dimensions, we deduce that the hydrophobic triterpenoid rings of
      the saponin molecules lie parallel to the air-water interface, with the
      hydrophilic glucoside tails protruding into the aqueous phase. Upon small
      deformation, the saponin adsorption layers exhibit a very high surface
      dilatational elasticity (280 +/- 30 mN/m), a much lower shear elasticity (26 +/-
      15 mN/m), and a negligible true dilatational surface viscosity. The measured
      dilatational elasticity is in very good agreement with the theoretical
      predictions of the Volmer adsorption model (260 mN/m). The measured
      characteristic adsorption time of the saponin molecules is 4 to 5 orders of
      magnitude longer than that predicted theoretically for diffusion-controlled
      adsorption, which means that the saponin adsorption is barrier-controlled around
      and above the cmc. The perturbed saponin layers relax toward equilibrium in a
      complex manner, with several relaxation times, the longest of them being around 3
      min. Molecular interpretations of the observed trends are proposed when possible.
      Surprisingly, in the course of our study we found experimentally that the drop
      shape analysis method (DSA method) shows a systematically lower surface
      elasticity, in comparison with the other two methods used: Langmuir trough and
      capillary pressure tensiometry with spherical drops. The possible reasons for the
      observed discrepancy are discussed, and the final conclusion is that the DSA
      method has specific problems and may give incorrect results when applied to study
      the dynamic properties of systems with high surface elasticity, such as
      adsorption layers of saponins, lipids, fatty acids, solid particles, and some
      proteins. The last conclusion is particularly important because the DSA method
      recently became the preferred method for the characterization of fluid interfaces
      because of its convenience.

PMID- 21894984
TI  - Encapsulation of the ethylene inhibitor 1-Methylcyclopropene by cucurbit[6]uril.
AB  - 1-Methylcyclopropene (1-MCP) is an excellent safe and commercially available
      ethylene antagonist for the preservation of horticultural products. However 1-MCP
      has to be stored in absorbents due to its gaseous and unstable characteristics.
      In this paper cucurbit[6]uril (CB[6]) was used as the absorbent to encapsulate 1
      MCP, and the resultant inclusion complex was characterized by IR, powder X-ray
      diffraction, thermal analysis, and fluorescent spectra. The effects of
      encapsulation conditions on the formation of inclusion complex were also
      investigated. The amount of 1-MCP encapsulated by CB[6] was about 4.5% by weight
      when the initial concentration of 1-MCP, encapsulation temperature, CB[6]
      concentration, and encapsulation time were set at 75 mL/L, 20  degrees C, 30 mM,
      and 8 h, respectively. Furthermore, the release of 1-MCP from the complex can be
      realized with different solutions such as sodium bicarbonate, benzoic acid, and
      distilled water. CB[6] can be used as an excellent absorbent for encapsulation of
      1-MCP.

PMID- 21894985
TI  - Explanation for main features of structure-genotoxicity relationships of aromatic
      amines by theoretical studies of their activation pathways in CYP1A2.
AB  - Aromatic and heteroaromatic amines (ArNH(2)) represent a class of potential
      mutagens that after being metabolically activated covalently modify DNA.
      Activation of ArNH(2) in many cases starts with N-hydroxylation by P450 enzymes,
      primarily CYP1A2. Poor understanding of structure-mutagenicity relationships of
      ArNH(2) limits their use in drug discovery programs. Key factors that facilitate
      activation of ArNH(2) are revealed by exploring their reaction intermediates in
      CYP1A2 using DFT calculations. On the basis of these calculations and extensive
      analysis of structure-mutagenicity data, we suggest that mutagenic metabolites
      are generated by ferric peroxo intermediate, (CYP1A2)Fe(III)-OO(-), in a three
      step heterolytic mechanism. First, the distal oxygen of the oxidant abstracts
      proton from H-bonded ArNH(2). The subsequent proximal protonation of the
      resulting (CYP1A2)Fe(III)-OOH weakens both the O-O and the O-H bonds of the
      oxidant. Heterolytic cleavage of the O-O bond leads to N-hydroxylation of ArNH(-)
      via S(N)2 mechanism, whereas cleavage of the O-H bond results in release of
      hydroperoxy radical. Thus, our proposed reaction offers a mechanistic explanation
      for previous observations that metabolism of aromatic amines could cause
      oxidative stress. The primary drivers for mutagenic potency of ArNH(2) are (i)
      binding affinity of ArNH(2) in the productive binding mode within the CYP1A2
      substrate cavity, (ii) resonance stabilization of the anionic forms of ArNH(2),
      and (iii) exothermicity of proton-assisted heterolytic cleavage of N-O bonds of
      hydroxylamines and their bioconjugates. This leads to a strategy for designing
      mutagenicity free ArNH(2): Structural alterations in ArNH(2), which disrupt
      geometric compatibility with CYP1A2, hinder proton abstraction, or strongly
      destabilize the nitrenium ion, in this order of priority, prevent genotoxicity.

PMID- 21894986
TI  - Electronic and structural properties of low-lying excited states of vitamin B12.
AB  - Time-dependent density functional theory (TD-DFT) has been applied to explore
      electronically excited states of vitamin B(12) (cyanocobalamin or CNCbl). To
      explain why the Co-C bond in CNCbl does not undergo photodissociation under
      conditions of simple photon excitation, electronically excited states have been
      computed along the Co-C(CN) stretched coordinate. It was found that the repulsive
      (3)(sigma(Co-C) -> sigma*(Co-C)) triplet state drops in energy as the Co-C(CN)
      bond lengthens, but it does not become dissociative. Low-lying excited states
      were also computed as function of two axial bond lengths. Two energy minima have
      been located on the S(1)/CNCbl, as well as T(1)/CNCbl, surfaces. The full
      geometry optimization was carried out for each minimum and electronic properties
      associated with each optimized structure were analyzed in details. One minimum
      was described as excitation having mixed pipi*/MLCT (metal-to-ligand charge
      transfer) character, while the second as ligand-to-metal charge transfer (LMCT)
      transition. Neither of them, however, can be viewed as pure MLCT or LMCT
      transitions since additional excitation to or from sigma-bonds (SB) of N-Co-C
      unit have also noticeable contributions. Inclusion of solvent altered the
      character of one of the excitations from pipi*/MLCT/SBLCT to pipi*/LMCT/LSBCT
      type, and therefore, both of them gained significant contribution from LMCT/LSBCT
      transition. Finally, the nature of S(1) electronic state has been comparatively
      analyzed in CNCbl and MeCbl cobalamins.

PMID- 21894987
TI  - Cu(2+)-assisted synthesis of hexoctahedral Au-Pd alloy nanocrystals with high
      index facets.
AB  - Controlled syntheses of multicomponent metal nanocrystals (NCs) and high-index
      surfaces have attracted increasing attention due to the specific physical and
      chemical properties of such NCs. Taking advantage of copper underpotential
      deposition as a bridge, hexoctahedral Au-Pd alloy NCs with {hkl} facets exposed
      were successfully synthesized, while phase separation occurred in the absence of
      Cu(2+) ions. The as-prepared hexoctahedral Au-Pd alloy NCs exhibited very
      excellent performance in terms of both formic acid electro-oxidation and methanol
      tolerance due to synergism between the high-index facets and the alloy.

PMID- 21894989
TI  - Bottom-up fabrication of photoluminescent graphene quantum dots with uniform
      morphology.
AB  - Multicolor photoluminescent graphene quantum dots (GQDs) with a uniform size of
      ~60 nm diameter and 2-3 nm thickness were prepared by using unsubstituted hexa
      peri-hexabenzocoronene as the carbon source. This result offers a new strategy to
      fabricate monodispersed GQDs with well-defined morphology.

PMID- 21894988
TI  - Ratio analysis nuclear magnetic resonance spectroscopy for selective metabolite
      identification in complex samples.
AB  - Metabolite identification in the complex NMR spectra of biological samples is a
      challenging task due to significant spectral overlap and limited signal-to-noise.
      In this study we present a new approach, RANSY (ratio analysis NMR spectroscopy),
      which identifies all the peaks of a specific metabolite on the basis of the
      ratios of peak heights or integrals. We show that the spectrum for an individual
      metabolite can be generated by exploiting the fact that the peak ratios for any
      metabolite in the NMR spectrum are fixed and proportional to the relative numbers
      of magnetically distinct protons. When the peak ratios are divided by their
      coefficients of variation derived from a set of NMR spectra, the generation of an
      individual metabolite spectrum is enabled. We first tested the performance of
      this approach using one-dimensional (1D) and two-dimensional (2D) NMR data of
      mixtures of synthetic analogues of common body fluid metabolites. Subsequently,
      the method was applied to (1)H NMR spectra of blood serum samples to demonstrate
      the selective identification of a number of metabolites. The RANSY approach,
      which does not need any additional NMR experiments for spectral simplification,
      is easy to perform and has the potential to aid in the identification of unknown
      metabolites using 1D or 2D NMR spectra in virtually any complex biological
      mixture.

PMID- 21894990
TI  - Critical role of peroxisome proliferator activated receptor-delta on body fat
      reduction in C57BL/6J and human apolipoprotein E2 transgenic mice fed delipidated
      soybean.
AB  - The consumption of soy protein and fiber reduces body fat accumulation; however,
      the mechanism of this effect has not been clearly understood. We investigated the
      antiobesogenic effect of soy protein and fiber in two different mouse models.
      Normolipidemic nonobese C57BL/6J and hyperlipidemic obese human apolipoprotein E2
      transgenic mice were fed either delipidated soybean (DLSB) containing soy protein
      and fiber or a control diet. The DLSB-fed mice showed a significant reduction in
      body weight gain and adiposity compared with controls, in both C57BL/6J and apoE2
      mice. All metabolic parameters were significantly improved in the DLSB group
      compared with controls: total cholesterol, low-density lipoprotein cholesterol,
      insulin, and leptin levels were significantly reduced. Adiponectin concentrations
      were significantly elevated, and glucose tolerance was improved. In both types of
      DLSB-fed mice, the specific induction of PPAR-delta protein expression was
      evident in muscle and adipose tissues. The expression of PPAR-delta target genes
      in the DLSB-fed mice was also significantly altered. Acetyl-CoA carboxylase-1 and
      fatty acid synthase levels in adipose tissue were downregulated, and uncoupling
      protein-2 in muscle was upregulated. Intestinal expression of fatty acid
      transport protein-4, cluster of differentiation-36, and acyl-CoA synthetase were
      significantly downregulated. We propose that marked activation of PPAR-delta is
      the primary mechanism mediating the antiobesogenic effect of soybean and that
      PPAR-delta has multiple actions: induction of thermogenesis in muscle, reduction
      of fatty acid synthesis in adipose tissue, and reduction of fatty acid uptake in
      intestinal tissue.

PMID- 21894991
TI  - Steam etched porous graphene oxide network for chemical sensing.
AB  - Oxidative etching of graphene flakes was observed to initiate from edges and the
      occasional defect sites in the basal plane, leading to reduced lateral size and a
      small number of etch pits. In contrast, etching of highly defective graphene
      oxide and its reduced form resulted in rapid homogeneous fracturing of the sheets
      into smaller pieces. On the basis of these observations, a slow and more
      controllable etching route was designed to produce nanoporous reduced graphene
      oxide sheets by hydrothermal steaming at 200  degrees C. The degree of etching
      and the concomitant porosity can be conveniently tuned by etching time. In
      contrast to nonporous reduced graphene oxide annealed at the same temperature,
      the steamed nanoporous graphene oxide exhibited nearly 2 orders of magnitude
      increase in the sensitivity and improved recovery time when used as chemiresistor
      sensor platform for NO(2) detection. The results underscore the efficacy of the
      highly distributed nanoporous network in the low temperature steam etched GO.

PMID- 21894993
TI  - Simple route to sterically pure diketopiperazines.

PMID- 21894992
TI  - Lipid binding to the carotenoid binding site in photosynthetic reaction centers.
AB  - Lipid binding to the carotenoid binding site near the inactive
      bacteriochlorophyll monomer was probed in the reaction centers of carotenoid-less
      mutant, R-26 from Rhodobacter sphaeroides. Recently, a marked light-induced
      change of the local dielectric constant in the vicinity of the inactive
      bacteriochlorophyll monomer was reported in wild type that was attributed to
      structural changes that ultimately lengthened the lifetime of the charge
      separated state by 3 orders of magnitude (Deshmukh, S. S.; Williams, J. C.;
      Allen, J. P.; Kalman, L. Biochemistry 2011, 50, 340). Here in the R-26 reaction
      centers, the combination of light-induced structural changes and lipid binding
      resulted in a 5 orders of magnitude increase in the lifetime of the charge
      separated state involving the oxidized dimer and the reduced primary quinone in
      proteoliposomes. Only saturated phospholipids with fatty acid chains of 12 and 14
      carbon atoms long were bound successfully at 8  degrees C by cooling the reaction
      center protein slowly from room temperature. In addition to reporting a dramatic
      increase of the lifetime of the charge-separated state at physiologically
      relevant temperatures, this study reveals a novel lipid binding site in
      photosynthetic reaction center. These results shed light on a new potential
      application of the reaction center in energy storage as a light-driven
      biocapacitor since the charges separated by ~30 A in a low-dielectric medium can
      be prevented from recombination for hours.

PMID- 21894994
TI  - One-pot synthesis of highly monodispersed ferrite nanocrystals: surface
      characterization and magnetic properties.
AB  - In the present study, a facile one-pot synthetic route, utilizing a strong polar
      organic solvent, N-methyl 2-pyrrolidone (NMP), is demonstrated to obtain highly
      monodispersed ferrite nanocrystals. The equimolar mixture of oleic acid,
      C(17)H(33)COOH (R-COOH), and oleylamine, C(18)H(35)NH(2) (R'-NH(2)), was used to
      coat the magnetic nanocrystals. Structural and magnetic properties of the ferrite
      nanocrystals were studied by a multitechnique approach including X-ray
      diffraction (XRD), high resolution transmission electron microscopy (HRTEM),
      Fourier transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA),
      X-ray photoelectron spectroscopy (XPS), vibrating sample magnetometry (VSM), and
      Mossbauer spectroscopy. FTIR spectral analysis indicates oleylamine helps in
      deprotonation of oleic acid, resulting in the formation of an acid-base complex,
      R-COO-:NH(3)(+)-R', which acts as binary capping agent. Structural and
      coordination differences of iron were studied by XPS and Mossbauer spectral
      analysis. XPS analysis was carried out to examine the oxidation state of iron
      ions in iron oxide nanocrystals. The presence of a magnetically dead layer (~0.38
      and ~0.67 nm) and a nonmagnetic organic coating (~2.3 and ~1.7 nm) may
      substantially reduce the saturation magnetization values for CoFe(2)O(4) and
      Fe(3)O(4) nanocrystals, respectively. The energy barrier distribution function of
      magnetic anisotropy was derived from the temperature dependent decay of
      magnetization. A very narrow energy barrier distribution elucidates that the
      ferrite nanocrystals obtained in this study are highly monodispersed.

PMID- 21894995
TI  - Copper nitride nanocubes: size-controlled synthesis and application as cathode
      catalyst in alkaline fuel cells.
AB  - Copper nitride nanocubes are synthesized in a facile one-phase process. The
      crystal size could be tuned easily by using different primary amines as capping
      agents. Such Pt-free nanocrystals exhibit electrocatalytic activity toward oxygen
      reduction and appear to be promising cathodic electrocatalysts in alkaline fuel
      cells.

PMID- 21894996
TI  - Fast photochemical oxidation of proteins for epitope mapping.
AB  - The growing use of monoclonal antibodies as therapeutics underscores the
      importance of epitope mapping as an essential step in characterizing antibody
      antigen complexes. The use of protein footprinting coupled with mass
      spectrometry, which is emerging as a tool in structural biology, offers
      opportunities to map antibody-binding regions of antigens. We report here the use
      of footprinting via fast photochemical oxidation of proteins (FPOP) with OH
      radicals to characterize the epitope of the serine protease thrombin. The data
      correlate well with previously published results that determined the epitope of
      thrombin. This study marks the first time oxidative labeling has been used for
      epitope mapping.

PMID- 21894997
TI  - Effects of anions on nanostructuring of cationic amphiphilic peptides.
AB  - The effects of addition of a series of stoichiometric salts on the
      nanostructuring of cationic amphiphilic peptides have been investigated through
      the combination of atomic force microscopy (AFM), circular dichroism (CD), and
      turbidity measurements. The results revealed that anions had more pronounced
      effects than cations in tuning the nanostructures formed from these peptides.
      Addition of ClO(3)(-), NO(3)(-), and Br(-) could stabilize the primary
      nanostructures (nanostacks, nanospheres, or short nanorods) formed by A(9)K and
      I(3)K and effectively inhibit their growth into longer nanostructures (nanorods
      or nanotubes). In contrast, the anions of Cl(-), SO(4)(2-), HPO(4)(2-), PO(4)(3
      ), and C(6)H(5)O(7)(3-) (citrate) favored the axial growth of these peptides to
      form long intersecting nanofibrils and led to an increase in diameter and surface
      roughness, as well, clearly enhancing their propensity for nanostructuring. The
      efficiency of different anions in promoting the growth of peptide nanoaggregates
      into larger ones could be ordered as ClO(3)(-) < NO(3)(-) <= Br(-) < Cl(-) <
      SO(4)(2-) < HPO(4)(2-) < PO(4)(3-) < C(6)H(5)O(7)(3-), broadly consistent with
      the Hofmeister anion sequence. These observations were well rationalized by
      considering different aspects of direct interactions of the anions with the
      peptide molecules.

PMID- 21894998
TI  - Ring-slippage and multielectron redox properties of Fe/Ru/Os-bis(arene)
      complexes: does hapticity change really cause potential inversion?
AB  - Bis(hexamethylbenzene) complexes of the group 8 metals (Fe, Ru, Os) show
      surprising diversity in their electron-transfer mechanisms and associated
      thermodynamics for the M(II) -> M(I) -> M(0) redox series. In electrochemical
      experiments, the Fe complex exhibits normally ordered potentials separated by ~1
      V, the Ru system shows nearly overlapping one-electron redox events, and Os
      demonstrates a one-step, two-electron transfer with a peak potential separation
      suggestive of highly inverted potentials. It has been conjectured that the
      sequential one-electron transfers observed for Fe are due to the lack of an
      accessible eta(4):eta(6) Fe(0) state, destabilizing the fully reduced species.
      Using an established model chemistry based on DFT, we demonstrate that the
      hapticity change is a consequence of the bonding throughout this transition metal
      triad and that apparent multielectron behavior is controlled by the vertical
      electron attachment component of the M(II) -> M(I) redox event. Furthermore, the
      eta(6):eta(6) Fe(0) triplet state is more favorable than the hypothetical
      eta(4):eta(6) singlet state, emphasizing that the hapticity change is not
      sufficient for multielectron behavior. Despite both displaying two-electron redox
      responses, Ru and Os traverse fundamentally different mechanisms based on whether
      the first (Os) or second (Ru) electron transfer induces the hapticity change.
      While the electronic structure analysis is limited to the Fe triad here, the
      conceptual model that we developed provides a general understanding of the redox
      behavior exhibited by d(6) bis(arene) compounds.

PMID- 21894999
TI  - Synthesis of ultrathin FePtPd nanowires and their use as catalysts for methanol
      oxidation reaction.
AB  - We report a facile synthesis of ultrathin (2.5 nm) trimetallic FePtPd alloy
      nanowires (NWs) with tunable compositions and controlled length (<100 nm). The
      NWs were made by thermal decomposition of Fe(CO)(5) and sequential reduction of
      Pt(acac)(2) (acac = acetylacetonate) and Pd(acac)(2) at temperatures from 160 to
      240  degrees C. These FePtPd NWs showed composition-dependent catalytic activity
      and stability for methanol oxidation reaction. Among FePtPd and FePt NWs as well
      as Pd, Pt, and PtPd nanoparticles (NPs) studied in 0.2 M methanol and 0.1 M
      HClO(4) solution, the Fe(28)Pt(38)Pd(34) NWs showed the highest activity, with
      their mass current density reaching 488.7 mA/mg Pt and peak potential for
      methanol oxidation decreasing to 0.614 V from 0.665 V (Pt NP catalyst). The NW
      catalysts were also more stable than the NP catalysts, with the
      Fe(28)Pt(38)Pd(34) NWs retaining the highest mass current density (98.1 mA/mg Pt)
      after a 2 h current-time test at 0.4 V. These trimetallic NWs are a promising new
      class of catalyst for methanol oxidation reaction and for direct methanol fuel
      cell applications.

PMID- 21895000
TI  - Analysis of infrared spectra of beta-hairpin peptides as derived from molecular
      dynamics simulations.
AB  - Infrared temperature-dependent spectroscopy is a well-known tool to characterize
      folding/unfolding transitions in peptides and proteins, assuming that the higher
      the temperature, the higher the unfolded population. The infrared spectra at
      different temperatures of two beta-hairpin peptides (gramicidin S analogues GS6
      and GS10) are here reconstructed by means of molecular dynamics (MD) simulations
      and a theoretical-computational method based on the perturbed matrix method. The
      calculated temperature-dependent spectra result in good agreement with the
      experimental available spectra. The same methodology has been then used to
      reconstruct the spectra corresponding to the pure unfolded and folded states, as
      defined from the MD simulations, in order to better understand the temperature
      dependent spectra and to help the interpretation of the experimental spectra. For
      example, our results show that in the case of the GS6 peptide the analysis of the
      temperature-dependent spectra cannot be used to investigate the folding/unfolding
      kinetics within the usual assumption that the higher the temperature, the higher
      the probability of the unfolded state.

PMID- 21895001
TI  - Reversible hydrogen transfer reactions of cysteine thiyl radicals in peptides:
      the conversion of cysteine into dehydroalanine and alanine, and of alanine into
      dehydroalanine.
AB  - The photodissociation of disulfide bonds in model peptides containing Ala and Ala
      d(3) generates a series of photoproducts following the generation of a CysS(*)
      thiyl radical pair. These photoproducts include transformations of Cys to
      dehydroalanine (Dha) and Ala, as well as Ala to Dha. Intramolecular Michael
      addition of an intact Cys with a photolytically generated Dha results in the
      formation of cyclic thioethers. The conversion of Cys into Dha likely involves a
      1,3-H-shift from the Cys (alpha)C-H bond to the thiyl radical, followed by
      elimination of HS(*). The conversion of Dha into Ala most likely involves
      hydrated electrons, which are generated through the photolysis of Cys, the
      photoproduct of disulfide photolysis. Prior to stable product formation, CysS(*)
      radicals engage in reversible hydrogen transfer reactions with (alpha)C-H and
      (beta)C-H bonds of the surrounding amino acids. Especially for the (beta)C-H
      bonds of Ala, such hydrogen transfer reactions are unexpected on the basis of
      thermodynamic grounds; however, the replacement of deuterons in Ala-d(3) by
      hydrogens in H(2)O provides strong experimental evidence for such reactions.

PMID- 21895002
TI  - Hydrogen atom abstraction selectivity in the reactions of alkylamines with the
      benzyloxyl and cumyloxyl radicals. The importance of structure and of substrate
      radical hydrogen bonding.
AB  - A time-resolved kinetic study on the hydrogen abstraction reactions from a series
      of primary and secondary amines by the cumyloxyl (CumO(*)) and benzyloxyl
      (BnO(*)) radicals was carried out. The results were compared with those obtained
      previously for the corresponding reactions with tertiary amines. Very different
      hydrogen abstraction rate constants (k(H)) and intermolecular selectivities were
      observed for the reactions of the two radicals. With CumO(*), k(H) was observed
      to decrease on going from the tertiary to the secondary and primary amines. The
      lowest k(H) values were measured for the reactions with 2,2,6,6
      tetramethylpiperidine (TMP) and tert-octylamine (TOA), substrates that can only
      undergo N-H abstraction. The opposite behavior was observed for the reactions of
      BnO(*), where the k(H) values increased in the order tertiary < secondary <
      primary. The k(H) values for the reactions of BnO(*) were in all cases
      significantly higher than those measured for the corresponding reactions of
      CumO(*), and no significant difference in reactivity was observed between
      structurally related substrates that could undergo exclusive alpha-C-H and N-H
      abstraction. This different behavior is evidenced by the
      k(H)(BnO(*))/k(H)(CumO(*)) ratios that range from 55-85 and 267-673 for secondary
      and primary alkylamines up to 1182 and 3388 for TMP and TOA. The reactions of
      CumO(*) were described in all cases as direct hydrogen atom abstractions. With
      BnO(*) the results were interpreted in terms of the rate-determining formation of
      a hydrogen-bonded prereaction complex between the radical alpha-C-H and the amine
      lone pair wherein hydrogen abstraction occurs. Steric effects and amine HBA
      ability play a major role, whereas the strength of the substrate alpha-C-H and N
      H bonds involved appears to be relatively unimportant. The implications of these
      different mechanistic pictures are discussed.

PMID- 21895003
TI  - Wiring of redox enzymes on three dimensional self-assembled molecular scaffold.
AB  - The integration of biological molecules and nanoscale components provides a
      fertile basis for the construction of hybrid materials of synergic properties and
      functions. Stable protein 1 (SP1), a highly stable ring shaped protein, was
      recently used to display different functional domains, to bind nanoparticles
      (NPs), and to spontaneously form two and three-dimensional structures. Here we
      show an approach to wire redox enzymes on this self-assembled protein
      nanoparticle hybrid. Those hybrids are genetically engineered SP1s, displaying
      glucose oxidase (GOx) enzymes tethered to the protein inner pore. Moreover, the
      Au-NP-protein hybrids self-assembled to multiple enzymatic layers on the surface.
      By wiring the redox enzymes to the electrode, we present an active structure for
      the bioelectrocatalytic oxidation of glucose. This system demonstrates for the
      first time a three-dimensional assembly of multiple catalytic modules on a
      protein scaffold with an efficient electrical wiring of the enzyme units on an
      electrode surface, thus implementing a hybrid electrically active unit for
      nanobioelectronic applications.

PMID- 21895004
TI  - Methods for the preparation of allenes employing indium- and zinc-mediated
      dehalogenation reactions in aqueous solutions.
AB  - Simple and mild methods for the synthesis of allenes, employing indium- and zinc
      mediated dehalogenation reactions of vicinal dihalides in an aqueous solvent, are
      described. By using these procedures, various allenylmethyl aryl ethers and
      monosubstituted allenes have been prepared in good to excellent yields.

PMID- 21895005
TI  - Scalable synthesis of enantiomerically pure syn-2,3-dihydroxybutyrate by
      Sharpless asymmetric dihydroxylation of p-phenylbenzyl crotonate.
AB  - An efficient four-step synthetic route to the useful chiral building block
      (2R,3S)-dihydroxybutyric acid acetonide in >95% ee is detailed. The sequence is
      readily scaled, requires no chromatography, and allows for efficient recycling of
      p-phenylbenzyl alcohol, an expedient for enantio- and diastereoenrichment by
      recrystallization.

PMID- 21895006
TI  - Determining the orientation and molecular packing of organic dyes on a TiO2
      surface using X-ray reflectometry.
AB  - The determination of the orientation and molecular density for several porphyrin
      dyes adsorbed on planar TiO(2) surfaces using X-ray reflectometry (XRR) is
      reported. Adsorption of nanoscale water layers occurred rapidly upon exposure of
      freshly prepared TiO(2) surfaces to ambient conditions; however, this was
      successfully eliminated, resulting in clearly discernible adsorbed dye layers for
      sensitized surfaces. Adsorbed dye orientations, determined from computations
      constrained by the measured dye layer thickness, were calculated to have a
      binding tilt angle of 35 degrees -40 degrees . Combining the XXR data with the
      orientation models indicates that the porphyrins form densely packed surfaces
      with an intermolecular spacing of 3-4 A, consistent with pi-pi stacking
      interactions. Changes in the molecular size of probe dyes were reflected in
      corresponding changes in the measured dye layer thickness, confirming the ability
      of this technique to resolve small variations in dye layer thickness and
      consequently adsorption orientation. Application of these results to
      understanding the behavior of dye-sensitized devices is discussed.

PMID- 21895007
TI  - Novel tripeptides with alpha-glucosidase inhibitory activity isolated from silk
      cocoon hydrolysate.
AB  - Active compounds with antidiabetic potential were isolated from silk peptide E5K6
      by consecutive ultrafiltration and gel filtration using Biogel P-2 and RS-HPLC
      using a YMC-Pack Pro C18 column. The highest alpha-glucosidase inhibitory
      activity of silk peptide E5K6 resulted from fractions with MW <1 kDa. The
      activities of gel-filtered fractions from silk peptide E5K6 of <1 kDa were
      assayed in vitro, demonstrating that the fourth peak (F4) had the highest alpha
      glucosidase inhibitory activity (IC(50) = 37.1 mg/mL). F4 of silk peptide E5K6
      was separated by HPLC into two peaks. Moreover, the purified compounds were
      identified as Gly-Glu-Tyr (GEY, MW = 367 Da) and Gly-Tyr-Gly (GYG, MW = 295 Da)
      according to amino acid sequences, and their alpha-glucosidase inhibitory
      activities (IC(50)) were 2.7 and 1.5 mg/mL, respectively.

PMID- 21895008
TI  - Crystal polymorphism of propylammonium chloride and structural properties of its
      mixture with water.
AB  - The thermal behavior of propylammonium chloride (PAC) has been investigated by
      parallel beam X-ray powder diffraction in the 303-463 K thermal range. A
      polymorphic transition has been observed at 403 K, whereas the melting process
      starts at 438 K. The low-temperature (LT) polymorph is tetragonal, P4/n or
      P4/nmm, and a = 6.2429(2) A, c = 7.3830(3) A, and Z = 2. Thermal expansion is
      isotropic as the N...Cl interactions have components along the three
      crystallographic axes. At the transition temperature, a high-temperature (HT)
      polymorph was observed, with candidate space groups P23, Pm3, P432, P43m, and
      Pm3m and cell parameter a = 11.715(3) A, consistent with Z = 12. This phase has
      features reminiscent of those of plastic phases of molecular crystals. The
      structural properties of a PAC/water mixture at ambient conditions were also
      studied by using an integrated approach, which combines X-ray diffraction
      measurements and molecular dynamics simulations carried out with the SPC/E and
      TIP5P water models. By using a Cl-water Lennard-Jones parameter previously
      refined for a similar system, a very good agreement between the theoretical and
      experimental diffraction patterns was obtained, especially in the case of the
      TIP5P simulation. A complex structural behavior has been highlighted, in which
      cations and anions do not possess a completely closed hydration shell of their
      own, but rather "solvent-shared ion pairs" are formed, where one or more water
      molecules act as a bridge between the chloride and propylammonium ions.

PMID- 21895009
TI  - Getting more out of a Job plot: determination of reactant to product
      stoichiometry in cases of displacement reactions and n:n complex formation.
AB  - The method of continuous variation (often referred to as Job's method) is an easy
      and common method for the determination of the reactant stoichiometry of chemical
      equilibria. The traditional interpretation of Job plots has been limited to
      complex association equilibria of the type nA + mB ? A(n)B(m), while little focus
      has been placed upon displacement type reactions (e.g., A + B ? C + D), which can
      give Job plots that look quite similar. We developed a novel method that allows
      the user to accurately distinguish between 1:1 complex association, 2:2 complex
      association, and displacement reactions using nothing more than a pocket
      calculator. This method involves preparing a Job plot of the system under
      investigation (using regularly spaced mole fractions), normalizing the measured
      quantities (such as the concentration of A(n)B(m) or C for the above reactions)
      to their maximum value (i.e., at mole fraction 0.5), and determining the sum of
      the normalized values. This sum is then compared with theoretically predicted
      normalized sum values that depend on the nature of the equilibrium. The
      relationship between, on the one hand, the sum of the normalized values and, on
      the other hand, the reaction equilibrium constant and the concentration of the
      stock solutions used for the preparation of the Job plot is also explored. The
      use of this new technique for the interpretation of Job plots permits users to
      readily determine information that can be obtained otherwise only with laborious
      additional experiments, as illustrated by the analysis of four Job plots taken
      from the literature.

PMID- 21895011
TI  - 4-Aminobenzimidazole-1-methylthymine: a model for investigating Hoogsteen base
      pairing between adenine and thymine.
AB  - We report the infrared spectrum of the 4-aminobenzimidazole-1-methylthymine
      (4ABI:1MT) heterodimer, detected by femtosecond multiphoton ionization. Based on
      calculations of both the harmonic and the anharmonic frequencies, the observed
      vibrational spectrum is assigned to a structure that mimics the Hoogsteen base
      pairing of adenine and thymine. A notable observation made in the course of this
      study is that there is a significant imbalance in the observed strengths of the H
      bonds. While the N...H-N bond reveals a large red shift of >700 cm(-1) for the NH
      stretch frequency, the N-H...O bond is characterized by only a 50 cm(-1) shift.
      The importance of this observation in the formation of Hoogsteen duplexes by
      thymine-based oligonucleotides is discussed.

PMID- 21895010
TI  - A homogeneous, recyclable polymer support for Rh(I)-catalyzed C-C bond formation.
AB  - A robust and practical polymer-supported, homogeneous, recyclable biphephos
      rhodium(I) catalyst has been developed for C-C bond formation reactions. Control
      of polymer molecular weight allowed tuning of the polymer solubility such that
      the polymer-supported catalyst is soluble in nonpolar solvents and insoluble in
      polar solvents. Using the supported rhodium catalysts, addition of aryl and
      vinylboronic acids to the electrophiles such as enones, aldehydes, N-sulfonyl
      aldimines, and alkynes occurs smoothly to provide products in high yields.
      Additions of terminal alkynes to enones and industrially relevant
      hydroformylation reactions have also been successfully carried out. Studies show
      that the leaching of Rh from the polymer support is low and catalyst recycle can
      be achieved by simple precipitation and filtration.

PMID- 21895012
TI  - On the structure and stretching of microhydrated DNA.
AB  - The structure of short double-stranded DNA oligomers in complex with varied
      amounts of water is investigated with classical molecular dynamics. Free
      simulations are performed first and mechanical stress is switched on afterward,
      resembling the conditions of single-molecule conductivity experiments. Water as
      well as counterions are seen to contribute to the stabilization of double
      stranded DNA structure, and a collapse of the native DNA structure is observed
      upon the removal of a certain amount of water. Pulling with a moderate external
      force provides additional support to the double-stranded DNA structure, whereas
      larger forces lead to the overstretching transition followed by the separation of
      DNA strands, in a manner similar to that observed in fully hydrated DNA.

PMID- 21895013
TI  - Inductive effect: a quantum theory of atoms in molecules perspective.
AB  - Substituent effects are ubiquitous in chemistry and the most fundamental is the
      inductive effect. In this study, the so-called inductive effect was probed in
      derivatives of bicyclo[1.1.1]pentane-1-carboxylic acid using the isodesmic
      reaction energy of the acid-base deprotonation, calculated at the PBE0/6
      31++G(d,p) level of theory (used throughout). Although structure, molecular
      orbitals, and nuclear magnetic shielding parameters are discussed, the main focus
      of this study is the use of the quantum theory of atoms in molecules to analyze
      the electron density distribution. It was observed that the effect propagates via
      the manipulation of atomic dipole moments controlled by that of the substituent.
      As the dipole moment conforms to the principle of atomic transferability, it is
      found that the substituent dipole determined in simple systems (e.g., R-H) can be
      used to describe the effect upon the bicyclo[1.1.1]pentane-1-carboxylic acid
      system.

PMID- 21895015
TI  - Mechanistic considerations for C-C bond reductive coupling at a cobalt(III)
      center.
AB  - The diamagnetic cobalt(III) dimethyl complex, cis,mer-(PMe(3))(3)Co(CH(3))(2)I,
      was found to promote selective C-C bond formation, affording ethane and triplet
      (PMe(3))(3)CoI. The mechanism of reductive elimination has been investigated by a
      series of kinetic and isotopic-labeling experiments. Ethane formation proceeds
      with a rate constant of 3.1(5) * 10(-5) s(-1) (50  degrees C) and activation
      parameters of DeltaH(double dagger) = 31.4(8) kcal/mol and DeltaS(double dagger)
      = 17(3) eu. Addition of free trimethylphosphine or coordinating solvent strongly
      inhibits reductive elimination, indicating reversible phosphine dissociation
      prior to C-C bond-coupling. EXSY NMR analysis established a rate constant of 9(2)
      s(-1) for phosphine loss from cis,mer-(PMe(3))(3)Co(CH(3))(2)I. Radical trapping,
      crossover, and isotope effect experiments were consistent with a proposed
      mechanism for ethane extrusion where formation of an unobserved five-coordinate
      intermediate is followed by concerted C-C bond formation. An unusual
      intermolecular exchange of cobalt-methyl ligands was also observed by isotopic
      labeling.

PMID- 21895014
TI  - Structures, energies, and spin-spin coupling constants of methyl-substituted 1,3
      diborata-2,4-diphosphoniocyclobutanes: four-member B-P-B-P rings B2P2(CH3)(n)H(8
      n), with n = 0, 1, 2, 4.
AB  - An ab initio study has been carried out to determine the structures, relative
      stabilities, and spin-spin coupling constants of a set of 17 methyl-substituted
      1,3-diborata-2,4-diphosphoniocyclobutanes B(2)P(2)(CH(3))(n)H(8-n), for n = 0, 1,
      2, 4, with four-member B-P-B-P rings. The B-P-B-P rings are puckered in a
      butterfly conformation, in agreement with experimental data for related
      molecules. Isomers with the CH(3) group bonded to P are more stable than those
      with CH(3) bonded to B. If there is only one methyl group or if two methyl groups
      are bonded to two different P or B atoms, isomers with equatorial bonds are more
      stable than those with axial bonds. However, when two methyl groups are present,
      the gem isomers are the most stable for molecules B(2)P(2)(CH(3))(2)H(6) with P-C
      and B-C bonds, respectively. Transition structures present barriers to the
      interconversion of two equilibrium structures or to the interchange of axial and
      equatorial positions in the same isomer. These barriers are very low for the
      isomer with two methyl groups bonded to B in axial positions for the isomer with
      four axial bonds and for the isomer with geminal B-C bonds at both B atoms.
      Coupling constants (1)J(B-P), (1)J(P-C), (1)J(B-C), (2)J(P-P), and (3)J(P-C) are
      capable of providing structural information. They are sensitive to the number of
      methyl groups present and can discriminate between axial, equatorial, and geminal
      bonds, although not all do this to the same extent. The one-bond coupling
      constants (1)J(B-P), (1)J(P-C), and (1)J(B-C) are similar in equilibrium and
      transition structures, but (3)J(P-C) and (2)J(P-P) are not. These coupling
      constants and those of the corresponding fluoro-derivatives of the 1,3-diborata
      2,4-diphosphoniocyclobutanes demonstrate the great sensitivity of phosphorus
      coupling to structural and electronic effects.

PMID- 21895017
TI  - Do H-bond features of silica surfaces affect the H2O and NH3 adsorption? Insights
      from periodic B3LYP calculations.
AB  - The adsorption of a single H(2)O and NH(3) molecule on different fully
      hydroxylated alpha-quartz, cristobalite, and tridymite surfaces has been studied
      at the B3LYP level of theory, within a periodic approach using basis sets of
      polarized triple-zeta quality and accounting for basis set superposition error
      (BSSE). Fully hydroxylated crystalline silica exhibits SiOH as terminal groups
      whose distribution and H-bond features depend on both the considered silica
      polymorph and the crystallographic plane, which gives rise to isolated, H-bond
      interacting SiOH pairs or infinitely connected H-bond chains. A key point of the
      present study is to understand how the H-bond features of a dry crystalline
      silica surface influence its adsorption properties. Results reveal that the
      silica-adsorbate (H(2)O and NH(3)) interaction energy anticorrelates with the
      density of SiOH groups at the surface. This counterintuitive observation arises
      from the fact that pre-existing H-bonds of the dry surface need to be broken to
      establish new H-bonds between the surface and the adsorbate, which manifests in a
      sizable energy cost due to surface deformation. A simple method is also proposed
      to estimate the strength of the pre-existing H-bonds at the dry surfaces, which
      is shown to anticorrelate with the adsorbate interaction energy, in agreement
      with the above trends.

PMID- 21895016
TI  - Structure-based design of pseudopeptidic inhibitors for SIRT1 and SIRT2.
AB  - The lack of substrate-bound crystal structures of SIRT1 and SIRT2 complicates the
      drug design for these targets. In this work, we aim to study whether SIRT3 could
      serve as a target structure in the design of substrate based pseudopeptidic
      inhibitors of SIRT1 and SIRT2. We created a binding hypothesis for pseudopeptidic
      inhibitors, synthesized a series of inhibitors, and studied how well the
      fulfillment of the binding criteria proposed by the hypothesis correlated with
      the in vitro inhibitory activities. The chosen approach was further validated by
      studying docking results between 12 different SIRT3, Sir2Tm, SIRT1 and SIRT2 X
      ray structures and homology models in different conformational forms. It was
      concluded that the created binding hypothesis can be used in the design of the
      substrate based inhibitors of SIRT1 and SIRT2 although there are some
      reservations, and it is better to use the substrate-bound structure of SIRT3
      instead of the available apo-SIRT2 as the target structure.

PMID- 21895018
TI  - Copper-mediated cyanation of aryl halide with the combined cyanide source.
AB  - A simple copper-mediated cyanation of aryl halide with the combination of
      ammonium bicarbonate and N,N-dimethylformamide as a cyanide source is achieved,
      providing nitriles in moderate to good yields. This new approach represents an
      exceedingly practical and safe method for the synthesis of aryl nitriles.

PMID- 21895019
TI  - Highly facialselective synthesis of pyranose 1,3-oxazines and their ring opening
      with nucleophiles: a novel entry to 2-C-branched glycosides.
AB  - A TMSOTf-promoted cycloaddition of N-benzoyl-N,O-acetals with various glycals and
      3-deoxy glycals affords pyranose 1,3-oxazines with high facial selectivity. In
      addition, a highly diastereoselective ring opening of the resulting pyranose 1,3
      oxazines is reported. With diverse nucleophiles, these reactions take place upon
      heating at 80  degrees C. This novel ring-opening reaction affords structurally
      diversified 2-C-branched glycosides with three newly formed contiguous
      stereocenters.

PMID- 21895021
TI  - Correlating humidity-dependent ionically conductive surface area with transport
      phenomena in proton-exchange membranes.
AB  - The objective of this effort was to correlate the local surface ionic conductance
      of a Nafion 212 proton-exchange membrane with its bulk and interfacial transport
      properties as a function of water content. Both macroscopic and microscopic
      proton conductivities were investigated at different relative humidity levels,
      using direct-current voltammetry and current-sensing atomic force microscopy
      (CSAFM). We were able to identify small ion-conducting domains that grew with
      humidity at the surface of the membrane. Numerical analysis of the surface ionic
      conductance images recorded at various relative humidity levels helped determine
      the fractional area of ion-conducting active sites. A simple square-root
      relationship between the fractional conducting area and observed interfacial mass
      transport resistance was established. Furthermore, the relationship between the
      bulk ionic conductivity and surface ionic conductance pattern of the Nafion
      membrane was examined.

PMID- 21895020
TI  - Enantiodivergent synthetic entry to the quinolizidine alkaloid lasubine II.
AB  - Intramolecular cycloaddition of the syn- and the anti-nitrone 9 and 13 leads
      stereoselectively to the azabicyclic compounds 10 and 14 which may provide access
      to both enantiomers of the quinolizidine alkaloid lasubine II.

PMID- 21895022
TI  - Pore with gate: enhancement of the isosteric heat of adsorption of dihydrogen via
      postsynthetic cation exchange in metal-organic frameworks.
AB  - Three isostructural anionic frameworks
      {[(Hdma)(H(3)O)][In(2)(L(1))(2)].4DMF.5H(2)O}(infinity) (NOTT-206-solv),
      {[H(2)ppz][In(2)(L(2))(2)].3.5DMF.5H(2)O}(infinity) (NOTT-200-solv), and
      {[H(2)ppz][In(2)(L(3))(2)].4DMF.5.5H(2)O}(infinity) (NOTT-208-solv) (dma =
      dimethylamine; ppz = piperazine) each featuring organic countercations that
      selectively block the channels and act as pore gates have been prepared. The
      organic cations within the as-synthesized frameworks can be replaced by Li(+)
      ions to yield the corresponding Li(+)-containing frameworks
      {Li(1.2)(H(3)O)(0.8)[In(2)(L(1))(2)].14H(2)O}(infinity) (NOTT-207-solv),
      {Li(1.5)(H(3)O)(0.5)[In(2)(L(2))(2)].11H(2)O}(infinity) (NOTT-201-solv), and
      {Li(1.4)(H(3)O)(0.6)[In(2)(L(3))(2)].4acetone.11H(2)O}(infinity) (NOTT-209-solv)
      in which the pores are now unblocked. The desolvated framework materials NOTT
      200a, NOTT-206a, and NOTT-208a display nonporous, hysteretic and reversible N(2)
      uptakes, respectively, while NOTT-206a and NOTT-200a provide a strong kinetic
      trap showing adsorption/desorption hysteresis with H(2). Single crystal X-ray
      analysis confirms that the Li(+) ions are either tetrahedrally (in NOTT-201-solv
      and NOTT-209-solv) or octahedrally (in NOTT-207-solv) coordinated by carboxylate
      oxygen atoms and/or water molecules. This is supported by (7)Li solid-state NMR
      spectroscopy. NOTT-209a, compared with NOTT-208a, shows a 31% enhancement in H(2)
      storage capacity coupled to a 38% increase in the isosteric heat of adsorption to
      12 kJ/mol at zero coverage. Thus, by modulating the pore environment via
      postsynthetic cation exchange, the gas adsorption properties of the resultant MOF
      can be fine-tuned. This affords a methodology for the development of high
      capacity storage materials that may operate at more ambient temperatures.

PMID- 21895024
TI  - Advances in optical imaging in cancer research--Part 1.

PMID- 21895023
TI  - Seminaphthofluorescein-based fluorescent probes for imaging nitric oxide in live
      cells.
AB  - Fluorescent turn-on probes for nitric oxide based on seminaphthofluorescein
      scaffolds were prepared and spectroscopically characterized. The Cu(II) complexes
      of these fluorescent probes react with NO under anaerobic conditions to yield a
      20-45-fold increase in integrated emission. The seminaphthofluorescein-based
      probes emit at longer wavelengths than the parent FL1 and FL2 fluorescein-based
      generations of NO probes, maintaining emission maxima between 550 and 625 nm. The
      emission profiles depend on the excitation wavelength; maximum fluorescence turn
      on is achieved at excitations between 535 and 575 nm. The probes are highly
      selective for NO over other biologically relevant reactive nitrogen and oxygen
      species including NO(3)(-), NO(2)(-), HNO, ONOO(-), NO(2), OCl(-), and H(2)O(2).
      The seminaphthofluorescein-based probes can be used to visualize endogenously
      produced NO in live cells, as demonstrated using Raw 264.7 macrophages.

PMID- 21895025
TI  - Time-resolved optical mammography and its preliminary clinical results.
AB  - We have been developing an optical mammography prototype consisting of a multi
      channel time-resolved spectroscopy system for breast cancer screening. The system
      utilizes the time-correlated single photon counting method, and the detector
      modules and the signal processing circuits were custom-made to obtain a high
      signal to noise ratio and high temperature stability with a high temporal
      resolution. Pulsed light generated by a Ti: Sapphire laser was irradiated to the
      breast, and the transmitted light was collected by optical fibers placed on the
      surface of a hemispherical gantry filled with an optical matching fluid. To
      reconstruct a 3D image of the breast, we employed a method using a time-resolved
      photon path distribution based on the assumption that scattering and absorption
      are independent of each other. We verified the possibility of human breast
      imaging by using a three-dimensional phantom model, which provides a simulation
      of human breast cancer, in the gantry. The clinical study was also started in
      January 2007. In a comparative study with conventional modalities, the breast
      cancers were detected as regions of optically higher absorption. Moreover, the
      results suggest that optical mammography is useful in monitoring the effects of
      chemotherapy.

PMID- 21895026
TI  - The utility of direct-current as compared to frequency domain measurements in
      spectrally-constrained diffuse optical tomography toward cancer imaging.
AB  - This work investigates, by means of analytical and simulation studies, the
      performance of spectrally-constrained image reconstruction in Continuous-Wave or
      Direct-Current (DC) and Frequency Domain (FD) near-infrared optical tomography. A
      recent analytic approach for estimating the accuracy of target recovery and the
      level of background artifact for optical tomography at single wavelength, based
      on the analysis of parametric reconstruction uncertainty level (PRUL), is
      extended to spectrally-constrained optical tomography. The analytical model is
      implemented to rank three sets of wavelengths that had been used as spectral
      prior in an independent experimental study. Subsequent simulation appraises the
      recovery of oxygenated hemoglobin (HbO), deoxygenated hemoglobin (Hb), water
      (H2O), scattering amplitude (A), and scattering power (b) using DC-only, DC
      excluded FD, and DC-included FD, based on the three sets of wavelengths as the
      spectral prior. The simulation results support the analytic ranking of the
      performance of the three sets of spectral priors, and generally agree with the
      performance outcome of DC-only versus that of DC-excluded FD and DC-included FD.
      Specifically, this study indicate that: 1) the rank of overall quality of
      chromophore recovery is Hb, H2O, and HbO from the highest to lowest; and in the
      scattering part the A is always better recovered than b. This outcome does
      suggest that the DC-only information gives rise to unique solution to the image
      reconstruction routine under the given spectral prior. 2) DC-information is not
      redundant in FD-reconstruction, as the artifact levels of DC-included FD
      reconstruction are always lower than those of DC-excluded FD. 3) The artifact
      level as represented by the noise-to-contrast-ratio is almost always the lowest
      in DC-only, leading to generally better resolution of multiple targets of
      identical contrasts over the background than in FD. However, the FD could
      outperform DC in the recovery of scattering properties including both A and b
      when the spectral prior is less optimal, implying the benefit of phase
      information in scattering recovery in the context of spectrally-constrained
      optical tomography.

PMID- 21895027
TI  - Imaging tumor oxyhemoglobin and deoxyhemoglobin concentrations with ultrasound
      guided diffuse optical tomography.
AB  - We present an ultrasound (US)-guided diffuse optical tomography for mapping tumor
      deoxyhemoglobin (deoxyHb) and oxyhemoglobin (oxyHb) concentrations in blood
      phantoms and in in-vivo patients. Because oxyHb and deoxyHb respond differently
      at different wavelengths, four laser diodes of wavelengths 740 nm, 780 nm, 808 nm
      and 830 nm were used in the study. Tumor model experiments were performed using
      phantoms of different hemoglobin oxygen saturations (14%-89%) representing
      hemoglobin oxygenation in tissue. Targets of different sizes and located at
      different depths were used to validate the accuracy of oxygen saturation
      estimation. The absolute deviations between the estimated hemoglobin oxygen
      saturations obtained from reconstructed absorption maps and oxygen measurements
      obtained using a pO2 electrode were less than 8% over the measured range of
      oxygen saturation. An inhomogeneous concentric blood phantom of deoxygenated
      center core and oxygenated outer shell was imaged and deoxyHb and oxyHb maps
      revealed corresponding distributions which correlated well with inhomogeneous
      deoxy- and oxy- distributions frequently seen in breast cancers. Clinical
      examples are given to demonstrate the utility of US-guided optical tomography in
      mapping heterogeneous deoxyHb and oxyHb distributions in breast cancers.

PMID- 21895029
TI  - Automated diagnosis of oral cancer using higher order spectra features and local
      binary pattern: a comparative study.
AB  - In the field of quantitative microscopy, textural information plays a significant
      role very often in tissue characterization and diagnosis, in addition to
      morphology and intensity. The objective of this work is to improve the
      classification accuracy based on textural features for the development of a
      computer assisted screening of oral sub-mucous fibrosis (OSF). In fact, the
      approach introduced is used to grade the histopathological tissue sections into
      normal, OSF without dysplasia (OSFWD) and OSF with dysplasia (OSFD), which would
      help the oral onco-pathologists to screen the subjects rapidly. The main
      objective of this work is to evaluate the use of Higher Order Spectra (HOS)
      features and Local Binary Pattern (LBP) features extracted from the epithelial
      layer in classifying normal, OSFWD and OSFD. For this purpose, we extracted
      twenty three HOS features and nine LBP features and fed them to a Support Vector
      Machine (SVM) for automated diagnosis. One hundred and fifty eight images (90
      normal, 42 OSFWD and 26 OSFD images) were used for analysis. LBP features provide
      a good sensitivity of 82.85% and specificity of 87.84%, and the HOS features
      provide higher values of sensitivity (94.07%) and specificity (93.33%) using SVM
      classifier. The proposed system, can be used as an adjunct tool by the onco
      pathologists to cross-check their diagnosis.

PMID- 21895028
TI  - Pre-clinical evaluation of fluorescent deoxyglucose as a topical contrast agent
      for the detection of Barrett's-associated neoplasia during confocal imaging.
AB  - The availability of confocal endomicroscopy motivates the development of optical
      contrast agents that can delineate the morphologic and metabolic features of
      gastrointestinal neoplasia. This study evaluates 2-NBDG, a fluorescent
      deoxyglucose, the uptake of which is associated with increased metabolic
      activity, in the identification of Barrett's-associated neoplasia. Surveillance
      biopsies from patients with varying pathologic grades of Barrett's esophagus were
      incubated ex vivo at 37 degrees C with 2-NBDG and imaged with a fluorescence
      confocal microscope. Images were categorized as neoplastic (high grade dysplasia,
      esophageal adenocarcinoma) or metaplastic (intestinal metaplasia, low grade
      dysplasia) based on the degree of glandular 2-NBDG uptake. Classification
      accuracy was assessed using histopathology as the gold standard. Forty-four
      biopsies were obtained from twenty-six patients; 206 sites were imaged. The
      glandular mean fluorescence intensity of neoplastic sites was significantly
      higher than that of metaplastic sites (p<0.001). Chronic inflammation was
      associated with increased 2-NBDG uptake in the lamina propria but not in
      glandular epithelium. Sites could be classified as neoplastic or not with 96%
      sensitivity and 90% specificity based on glandular mean fluorescence intensity.
      Classification accuracy was not affected by the presence of inflammation. By
      delineating the metabolic and morphologic features of neoplasia, 2-NBDG shows
      promise as a topical contrast agent for confocal imaging. Further in vivo testing
      is needed to determine its performance in identifying neoplasia during confocal
      endomicroscopic imaging.

PMID- 21895030
TI  - Fiber confocal back-scattering micro-spectral analysis for single cell.
AB  - A fiber confocal back scattering micro-spectrometer (FCBS) was established, which
      combined fiber confocal microscopy with light scattering spectroscopy (LSS) for
      early diagnosis of the cancer cell at cellular level. An adherent monolayer human
      normal gastric epithelium line GES-1 and a carcinoma cell line NCI-N87 as well as
      a normal liver cell line L02 and a high-metastatic-potential hepatocellular
      carcinoma cell line HCC-LM3 were measured respectively. The spectral results
      showed that micro-back-scattering intensity from GES-1 cell and L02 cell
      possessed interesting oscillations in contrast to NCI-N87 and HCC-LM3 cells.
      There was significant difference between the spectra of the normal and the cancer
      cells (p<0.001). This demonstrates that the FCBS system here is able to
      distinguish dysplastic cells from normal cells at cellular level.

PMID- 21895031
TI  - Identification of in vitro electropermeabilization equivalent pulse protocols.
AB  - Exposure of cells to an external sufficiently strong electric field results in
      the formation of pores across the membrane. This phenomenon, termed
      electropermeabilization, permits the transport of poorly permeant molecules into
      cytosol. In clinical practice, cell membrane permeabilization for drug
      electrotransfer is achieved using the ESOPE pulse protocol (1000 V/cm, 8 pulses,
      100 MUs, 5 kHz). The aim of this study was to investigate several combinations of
      electric field amplitude and pulse number able to induce electropermeabilization
      as the one observed when the ESOPE protocol was applied. Decreasing electric
      field amplitudes (1000 to 300 V/cm) in combination with increasing number of
      pulses (8 to 320) were applied to in vitro MG63 cells. Propidium iodide and
      Calcein blue AM uptake were used to evaluate cell electropermeabilization and
      viability. Results showed that the threshold of local electric field needed to
      obtain electropermeabilization decreased exponentially with increasing the number
      of pulses delivered (r2 5 0.92, p<0.0001). The absorbed dose threshold was
      dependent on the number of pulses for each voltage applied (r2 5 0.96, p<0.0001).
      In conclusion, the possibility of applying an increased number of pulses rather
      than increasing the electric field amplitude to perform electropermeabilization,
      may become an important tool for electropermeabilization-related clinical
      applications.

PMID- 21895033
TI  - 3D-conformal RT, fixed-field IMRT and RapidArc, which one is better for
      esophageal carcinoma treated with elective nodal irradiation.
AB  - The purpose of this study is to compare the characteristics of 3D-conformal
      radiotherapy (3D-CRT), fixed-field intensity-modulated radiotherapy (IMRT) and
      RapidArc for esophageal squamous cell carcinoma (ESCC) treated with elective
      nodal irradiation (ENI). CT datasets of 20 patients with ESCC were included and
      plans for single and double arcs of RapidArc (RA1 and RA2), 7-field IMRT and 3D
      CRT were created and optimized for each patient. The goal was to deliver 59.6 Gy
      to >=95% of the planning target volume (40 Gy to electively irradiated lymph
      nodal regions) while meeting the same normal-tissue dose constraints. The plans
      were compared based on dosimetric characteristics of target and organs at risk
      (OARs), monitor units (MUs), and appraised beam-on time. Both RA2 and IMRT
      resulted in similar target coverage (V95%, 97.84+/-1.50% for RA2 versus 96.96+/
      1.15% for IMRT), homogeneity index (HI, 0.11+/-0.02 for RA2 versus 0.10+/-0.01
      for IMRT) and conformity index (CI, 0.81+/-0.03 for RA2 versus 0.79+/-0.04 for
      IMRT), which displayed slightly better than single arc (V95%=94.55+/-1.50%,
      HI=0.12+/-0.02, CI=0.80+/-0.02) and much better than 3D-CRT (V95%=91.17+/-2.89%,
      HI=0.15+/-0.03, CI=0.60+/-0.07). The total lung V20, V30 was reduced
      approximately from 31%, 16% (3D-CRT) to 22%, 13% (IMRT) and 20%, 12% (RA2); the
      heart V30, V40 from 29%, 21% (3D-CRT) to 28%, 20% (IMRT) and 27%, 18% (RA2). The
      maximum dose to the spinal cord was 44.26+/-2.60 Gy for 3D-CRT, 42.47+/-2.40 Gy
      for IMRT, and 42.79+/-1.81 Gy for RA2. The number of MUs per fraction reduced
      from 990+/-165 (IMRT) to 503+/-70 (3D-CRT) and 502+/-79 (RA2). Appraised beam-on
      time of RapidArc was 1.2-2.4 min, which was lower than IMRT with 5.4 min by
      average. RapidArc, especially for double arcs plan could provide slight
      improvements in OARs sparing and lower MUs without compromised target qualities
      compared with IMRT, which was much better than 3D-CRT for ESCC treated with ENI.

PMID- 21895034
TI  - Changes in position and volume of lung cancer target volumes during stereotactic
      body radiotherapy (SBRT): is image guidance necessary?
AB  - The purpose of this study was to analyze inter- and intra-fractional changes in
      tumor volume with respect to both spatial and volumetric parameters among
      patients treated by SBRT for lung cancer. Twelve patients (13 tumors) were
      treated by SBRT with abdominal compression in 3-5 fractions over a 2 week period
      to a median dose of 60 Gy (range, 48 to 60 Gy). Kilovoltage cone-beam CT (CBCT)
      was obtained prior to the delivery of each fraction as well as intra-fractionally
      yielding a total of 55 CBCT scans. All CBCT scans were registered with the
      planning CT for target alignment and shifts were recorded and analyzed.
      Retrospectively, gross tumor volume (GTV) was contoured on all CBCT images and
      compared to initial planning volumes; positional differences were evaluated
      utilizing directional and vector analysis. Shifts greater than 5 mm were applied
      inter-fractionally in 6.8% (lateral), 29.5% (longitudinal), and 6.8% (vertical)
      of all delivered treatments. Using a 10 mm threshold, the corresponding
      percentages were 2.3%, 13.6%, and 2.3%, respectively. Across all fractions, the
      calculated inter-fractional shift vectors ranged from 0 to 31.2 mm, with 40.9%,
      15.9%, and 11.4% of all fractions having shift vectors>=5 mm, >=10 mm, and >=20
      mm, respectively. Intra-fractional shifts were also evaluated and found
      negligible in a small portion of patients evaluated. The mean overall reduction
      in GTV was 21.1% during SBRT. Significant changes in both position and volume
      occur during SBRT for lung cancer. Shifts (particularly in the superior-inferior
      axis) may exceed applied margins and compromise target coverage. Due to the
      extreme hypofractionation associated with SBRT, inter-fractional image guidance
      is necessary.

PMID- 21895032
TI  - Electrochemotherapy: a new technological approach in treatment of metastases in
      the liver.
AB  - Electrochemotherapy is now in development for treatment of deep-seated tumors,
      like in bones and internal organs, such as liver. The technology is available
      with a newly developed electric pulse generator and long needle electrodes;
      however the procedures for the treatment are not standardized yet. In order to
      describe the treatment procedure, including treatment planning, within the
      ongoing clinical study, a case of successful treatment of a solitary metastasis
      in the liver of colorectal cancer is presented. The procedure was performed
      intraoperatively by inserting long needle electrodes, two in the center of the
      tumor and four around the tumor into the normal tissue. The insertion of
      electrodes proved to be feasible and was done according to the treatment plan,
      prepared by numerical modeling. After intravenous bolus injection of bleomycin
      the tumor was exposed to electric pulses. The delivery of the electric pulses did
      not interfere with functioning of the heart, since the pulses were synchronized
      with electrocardiogram in order to be delivered outside the vulnerable period of
      the ventricles. Also the post treatment period was uneventful without side
      effects. Re-operation of the treated metastasis demonstrated feasibility of the
      reoperation, without secondary effects of electrochemotherapy on normal tissue.
      Good antitumor effectiveness with complete tumor destruction was confirmed with
      histological analysis. The patient is disease-free 16 months after the procedure.
      In conclusion, treatment procedure for electrochemotherapy proved to be a
      feasible technological approach for treatment of liver metastasis. Due to the
      absence of the side effects and the first complete destruction of the treated
      tumor, treatment procedure for electrochemotherapy seems to be a safe method for
      treatment of liver metastases with good treatment effectiveness even in difficult
      to-reach locations.

PMID- 21895035
TI  - Pharmacometrics for regulatory decision making: status and perspective.

PMID- 21895036
TI  - Impact of pharmacometric analyses on new drug approval and labelling decisions: a
      review of 198 submissions between 2000 and 2008.
AB  - Pharmacometric analyses have become an increasingly important component of New
      Drug Application (NDA) and Biological License Application (BLA) submissions to
      the US FDA to support drug approval, labelling and trial design decisions.
      Pharmacometrics is defined as a science that quantifies drug, disease and trial
      information to aid drug development, therapeutic decisions and/or regulatory
      decisions. In this report, we present the results of a survey evaluating the
      impact of pharmacometric analyses on regulatory decisions for 198 submissions
      during the period from 2000 to 2008. Pharmacometric review of NDAs included
      independent, quantitative analyses by FDA pharmacometricians, even when such
      analysis was not conducted by the sponsor, as well as evaluation of the sponsor's
      report. During 2000-2008, the number of reviews with pharmacometric analyses
      increased dramatically and the number of reviews with an impact on approval and
      labelling also increased in a similar fashion. We also present the impact of
      pharmacometric analyses on selection of paediatric dosing regimens, approval of
      regimens that had not been directly studied in clinical trials and provision of
      evidence of effectiveness to support a single pivotal trial. Case studies are
      presented to better illustrate the role of pharmacometric analyses in regulatory
      decision making.

PMID- 21895038
TI  - A single-species approach considering additional physiological information for
      prediction of hepatic clearance of glycoprotein derivate therapeutics.
AB  - BACKGROUND AND OBJECTIVES: Existing methods for the prediction of human clearance
      of therapeutic proteins involve the use of allometry approaches. In general,
      these approaches have concentrated on the role of body weight, with only
      occasional attention given to more specific physiological parameters. The
      objective of this study was to develop a mechanism-based model of hepatic
      clearance (CL(H)), which combines a single-species scaling approach with liver
      physiology, for predicting CL(H) of selected glycoprotein derivate therapeutics,
      and to compare the outcome of this novel method with those of two empirical
      methods obtained from the literature - namely, the single-exponent theory and
      multiple-species allometry. Thus, this study was designed as an explanatory study
      to verify if the addition of physiological information is of benefit for
      extrapolating clearance of selected therapeutic proteins from one species to
      another. METHODS: Five glycoprotein derivate therapeutics that are known to be
      principally eliminated by asialoglycoprotein receptors (ASGPRs) under in vivo
      conditions were selected. It was assumed that the interspecies differences in
      CL(H) reported for these compounds are reflected by the interspecies differences
      in the abundance of these receptors. Therefore, key scaling factors related to
      these differences were integrated into one model. Fourteen extrapolation
      (prediction) scenarios across species were used in this study while comparing the
      single-species model, based on physiology, with the single-exponent theory. In
      addition, the physiological model was compared with multiple-species allometry
      for three proteins. RESULTS: In general, the novel physiological model is
      superior to the derived allometric methods. Overall, the physiological model
      produced a predicted CL(H) value with levels of accuracy of 100% within 3-fold,
      100% within 2-fold and about 82% within 1.5-fold, compared with the observed
      values, whereas the levels of accuracy decreased to 93%, 77% and 53%,
      respectively, for allometry. The proposed physiological model is also superior to
      allometry on the basis of the root mean square error and absolute average fold
      error values. CONCLUSIONS: It has been demonstrated that interspecies differences
      in the abundance of ASGPRs principally govern interspecies variations in CL(H) of
      compounds that are principally eliminated by ASGPRs. Overall, the proposed
      physiological model is an additional tool, which should facilitate investigation
      and prediction of human CL(H) of specific glycoproteins solely on the basis of
      clearance data determined in a single preclinical species.

PMID- 21895037
TI  - Penetration of anti-infective agents into pulmonary epithelial lining fluid:
      focus on antibacterial agents.
AB  - The exposure-response relationship of anti-infective agents at the site of
      infection is currently being re-examined. Epithelial lining fluid (ELF) has been
      suggested as the site (compartment) of antimicrobial activity against lung
      infections caused by extracellular pathogens. There have been an extensive number
      of studies conducted during the past 20 years to determine drug penetration into
      ELF and to compare plasma and ELF concentrations of anti-infective agents. The
      majority of these studies estimated ELF drug concentrations by the method of urea
      dilution and involved either healthy adult subjects or patients undergoing
      diagnostic bronchoscopy. Antibacterial agents such as macrolides, ketolides,
      newer fluoroquinolones and oxazolidinones have ELF to plasma concentration ratios
      of >1. In comparison, beta-lactams, aminoglycosides and glycopeptides have ELF to
      plasma concentration ratios of <=1. Potential explanations (e.g. drug
      transporters, overestimation of the ELF volume, lysis of cells) for why these
      differences in ELF penetration occur among antibacterial classes need further
      investigation. The relationship between ELF concentrations and clinical outcomes
      has been under-studied. In vitro pharmacodynamic models, using simulated ELF and
      plasma concentrations, have been used to examine the eradication rates of
      resistant and susceptible pathogens and to explain why selected anti-infective
      agents (e.g. those with ELF to plasma concentration ratios of >1) are less likely
      to be associated with clinical treatment failures. Population pharmacokinetic
      modelling and Monte Carlo simulations have recently been used and permit ELF and
      plasma concentrations to be evaluated with regard to achievement of target
      attainment rates. These mathematical modelling techniques have also allowed
      further examination of drug doses and differences in the time courses of ELF and
      plasma concentrations as potential explanations for clinical and microbiological
      effects seen in clinical trials. Further studies are warranted in patients with
      lower respiratory tract infections to confirm and explore the relationships
      between ELF concentrations, clinical and microbiological outcomes, and
      pharmacodynamic parameters.

PMID- 21895043
TI  - These dermatological disorders share the features of being caused by
      hyperactivity of androgen within the pilosebaceous follicle, and although not
      life threatening are the source of a considerable psychological and emotional
      burden for patients. Foreword.

PMID- 21895039
TI  - Rivaroxaban: population pharmacokinetic analyses in patients treated for acute
      deep-vein thrombosis and exposure simulations in patients with atrial
      fibrillation treated for stroke prevention.
AB  - BACKGROUND AND OBJECTIVE: Rivaroxaban is an oral, direct Factor Xa inhibitor,
      which is at an advanced stage of clinical development for prevention and
      treatment of thromboembolic disorders. Two phase II studies, ODIXa-DVT and
      EINSTEIN DVT, assessed the efficacy and safety of oral rivaroxaban (once daily or
      twice daily) for treatment of acute deep-vein thrombosis (DVT). Population
      pharmacokinetic and pharmacodynamic analyses of rivaroxaban in patients in these
      two phase II studies were conducted to characterize the
      pharmacokinetics/pharmacodynamics of rivaroxaban and the relationship between
      important patient covariates and model parameters. Exposure simulations in
      patients with atrial fibrillation (AF) were also performed in order to predict
      the exposure of rivaroxaban, using modified demographic data reflecting the
      characteristics of a typical AF population. METHODS: A population pharmacokinetic
      model was developed using plasma samples from these patients. Various simulations
      were conducted to explore the pharmacokinetics of rivaroxaban in patients with
      DVT and to predict exposure in those with AF. Correlations between plasma
      rivaroxaban concentrations and the prothrombin time, Factor Xa activity,
      HepTest(r) and activated partial thromboplastin time were also described.
      RESULTS: The pharmacokinetics of rivaroxaban in patients with DVT were found to
      be consistent and predictable across all doses studied. The area under the plasma
      concentration-time curve (AUC) increased dose dependently. The same total daily
      doses given once daily achieved higher maximum plasma concentration (C(max))
      values (~20%) and lower trough (minimum) plasma concentration (C(trough)) values
      (~60%) than when given twice daily; however, the 5th-95th percentile ranges for
      these parameters overlapped. Rivaroxaban clearance was moderately influenced by
      age and renal function, and the volume of distribution was influenced by age,
      body weight and sex; the effects were within the observed interindividual
      variability. Simulations in virtual patient populations with AF showed that a
      rivaroxaban dose of 15 mg once daily in patients with creatinine clearance of 30
      49 mL/min would achieve AUC and C(max) values similar to those observed with 20
      mg once daily in patients with normal renal function. The prothrombin time
      correlated almost linearly with plasma rivaroxaban concentrations (<=500 MUg/L).
      CONCLUSION: Population analyses of phase II clinical data indicated that the
      pharmacokinetics and pharmacodynamics of all rivaroxaban doses were predictable
      and were affected by expected demographic factors in patients with acute DVT.

PMID- 21895044
TI  - Ethinylestradiol/Chlormadinone acetate: dermatological benefits.
AB  - Acne vulgaris, hirsutism, seborrhea and female pattern hair loss (FPHL) are
      common disorders of the pilosebaceous unit (PSU). In some women with
      hyperandrogenemia, an excess of androgens at the PSU can lead to the development
      of these dermatological manifestations. These manifestations can cause many
      psychiatric and psychological implications, such as social fears and anxiety, and
      can adversely affect quality of life. High androgen levels at the PSU as a
      possible underlying cause of acne vulgaris, hirsutism, seborrhea and FPHL
      supports the rationale for using combined oral contraceptives for the management
      of these conditions in women. The purpose of this review is to describe these
      dermatological manifestations of the PSU and the management of these conditions
      through the use of the oral contraceptive ethinylestradiol/chlormadinone acetate
      (EE/CMA). EE/CMA 0.03/2 mg is a combined monophasic contraceptive pill with anti
      androgenic properties. It is approved in Europe for contraception and has been
      investigated in phase III trials for the treatment of acne. EE/CMA was better
      than placebo and similar to another low-dose oral contraceptive
      (ethinylestradiol/levonorgestrel) in improving symptoms of acne in two phase III
      randomized controlled trials in patients with mild to moderate papulopustular
      acne. In addition, in trials investigating the contraceptive efficacy of EE/CMA,
      limited data suggest that there were also improvements in hirsutism, FPHL and
      seborrhea in small subgroups of patients. EE/CMA has a good safety profile. The
      most commonly reported adverse events are breast tenderness/pain,
      headache/migraine and nausea. Evidence in the literature indicates that the use
      of EE/CMA for the treatment of dermatological disorders under the control of
      androgens may be a valid treatment option. Further investigation is warranted.

PMID- 21895045
TI  - Ethinylestradiol/Chlormadinone acetate for use in dermatological disorders.
AB  - The diagnosis and management of four cases of dermatological disorders, most of
      which are related to the endocrine disorder of androgen excess, are presented.
      Combined oral contraceptives (COCs) may be useful when well-tolerated hormonal
      therapy and/or when contraception is required. A female patient with androgenetic
      alopecia or female pattern balding, without underlying hyperandrogenism, was
      treated with ethinylestradiol/chlormadinone acetate (EE/CMA) 0.03 mg/2 mg for 6
      months and experienced stabilization of hair loss (case report 1). A patient who
      had previously received a COC for an irregular menstrual pattern but again
      experienced irregular menses and also acne after stopping treatment was diagnosed
      with acne associated with polycystic ovary syndrome (PCOS) [case report 2]. After
      6 month's treatment with EE/CMA 0.03 mg/2 mg, this patient had fewer acne lesions
      and became eumenorrheic. A third patient who had excess hair since childhood was
      diagnosed with idiopathic hirsutism (no underlying gynecological or
      endocrinological disorder was found) and was treated with EE/CMA 0.03 mg/2 mg
      (case report 3). Less hair growth was reported after 6 months' treatment. Case
      report 4 describes a patient who presented with oligomenorrhea and acne. She was
      diagnosed with PCOS with acne, seborrhea and mild hirsutism. Treatment with
      EE/CMA 0.03 mg/2 mg for 6 months resulted in improvements in her facial acne,
      seborrhea and hirsutism; she also became eumenorrheic. These four cases
      illustrate that EE/CMA may be a useful and well tolerated treatment option in the
      management of patients with dermatological disorders with or without
      hyperandrogenization.

PMID- 21895048
TI  - Modern clinical management of arterial hypertension: fixed or free combination
      therapies? Foreword.

PMID- 21895050
TI  - Quasi-Gaussian beam analytical basis and comparison with an alternative approach
      (L).
AB  - A superposition of propagating Bessel beams was recently numerically demonstrated
      to approximate a Gaussian beam and was used to evaluate the scattering by a
      sphere centered on the focal point of the beam. An analytical beam synthesis used
      in optics by Agrawal and Pattanayak [J. Opt. Soc. Am. 69, 575-578 (1979)] is
      found here to be recovered as the weak focusing limit of the quasi-Gaussian beam
      when evanescent contributions are omitted from the analytical synthesis. The
      propagating-wave part of the analytical synthesis has similarities to, and
      differences from, the recent quasi-Gaussian approximation.

PMID- 21895049
TI  - Modern clinical management of arterial hypertension: fixed or free combination
      therapies?
AB  - Blood pressure control is a key element in any cardiovascular prevention
      strategy. However, it is also one of the least frequently achieved goals in
      modern strategies for the clinical management of cardiovascular diseases,
      resulting in high impact in terms of cardiovascular morbidity and mortality.
      Among different factors that can be identified as the causes of poor blood
      pressure (BP) control in the general population of patients with hypertension,
      the excessive use of monotherapy, as opposed to combination therapy, is arguably
      one of the most significant. In this perspective, the use of combination
      therapies having synergic and complementary actions has been shown to reduce BP
      levels to increase the percentage of patients who respond to antihypertensive
      treatment and achieve the recommended BP targets. Moreover, recent studies have
      demonstrated that these strategies provide effective protection against
      hypertension-related organ damage, as well as a significant reduction of major
      cardiovascular events. While currently available evidence supports an
      increasingly important role of combination therapies compared with monotherapies,
      several other issues remain to be clarified. Among these, it has not yet been
      clearly established which classes of drugs should be considered for combination
      strategies, at what doses each component should be used, and whether combination
      strategies may be definitively considered as a first choice for the treatment of
      hypertensive patients at cardiovascular risk. Another relevant aspect concerns
      the choice between fixed and free combination therapies. This article discusses
      and analyses the different factors that may contribute to achieve effective BP
      control. In particular, the potential benefits and drawbacks associated with the
      use of fixed versus free combination therapies for hypertension treatment will be
      examined and discussed. The benefits of using combination strategies based on
      drugs that antagonize the renin-angiotensin system and dihydropyridine calcium
      antagonists will also be discussed, with a particular focus on amlodipine
      besylate combination therapies.

PMID- 21895051
TI  - Beamforming with a circular array of microphones mounted on a rigid sphere (L).
AB  - Beamforming with uniform circular microphone arrays can be used for localizing
      sound sources over 360 degrees . Typically, the array microphones are suspended
      in free space or they are mounted on a solid cylinder. However, the cylinder is
      often considered to be infinitely long because the scattering problem has no
      exact solution for a finite cylinder. Alternatively one can use a solid sphere.
      This investigation compares the performance of a circular array mounded on a
      rigid sphere with that of such an array in free space and mounted on an infinite
      cylinder, using computer simulations. The examined techniques are delay-and-sum
      and circular harmonics beamforming, and the results are validated experimentally.

PMID- 21895052
TI  - The impact of reverberant self-masking and overlap-masking effects on speech
      intelligibility by cochlear implant listeners (L).
AB  - The purpose of this study is to determine the relative impact of reverberant self
      masking and overlap-masking effects on speech intelligibility by cochlear implant
      listeners. Sentences were presented in two conditions wherein reverberant
      consonant segments were replaced with clean consonants, and in another condition
      wherein reverberant vowel segments were replaced with clean vowels. The
      underlying assumption is that self-masking effects would dominate in the first
      condition, whereas overlap-masking effects would dominate in the second
      condition. Results indicated that the degradation of speech intelligibility in
      reverberant conditions is caused primarily by self-masking effects that give rise
      to flattened formant transitions.

PMID- 21895053
TI  - Fast asymptotic solutions for sound fields above and below a rigid porous ground.
AB  - The current study simultaneously addresses the problem of reflection and
      refraction of sound from a rigid porous ground surface. A more rigorous approach
      is used to derive more accurate asymptotic solutions that can be cast in a
      convenient form for ease of numerical implementations. The solutions provide
      means for rapid computations of the sound fields above and below the rigid porous
      ground. The improved asymptotic formulas for both situations agree well with
      numerical results obtained by other numerical schemes, which are more accurate
      but computationally more intensive. More importantly, the asymptotic solutions
      can be written in the well-known form of the Weyl-van der Pol formula, which
      provides a direct correlation between the reflected wave term for the sound field
      above the porous ground and the transmitted (refracted) wave term for the sound
      field below.

PMID- 21895054
TI  - On the use of Gegenbauer reconstructions for shock wave propagation modeling.
AB  - In therapeutic ultrasound, the presence of shock waves can be significant due to
      the use of high intensity beams, as well as due to shock formation during
      inertial cavitation. Although modeling of such strongly nonlinear waves can be
      carried out using spectral methods, such calculations are typically considered
      impractical, since accurate calculations often require hundreds or even thousands
      of harmonics to be considered, leading to prohibitive computational times.
      Instead, time-domain algorithms which generally utilize Godunov-type finite
      difference schemes are commonly used. Although these time domain methods can
      accurately model steep shock wave fronts, unlike spectral methods they are
      inherently unsuitable for modeling realistic tissue dispersion relations.
      Motivated by the need for a more general model, the use of Gegenbauer
      reconstructions as a postprocess tool to resolve the band-limitations of the
      spectral methods are investigated. The present work focuses on eliminating the
      Gibbs phenomenon when representing a steep wave front using a limited number of
      harmonics. Both plane wave and axisymmetric 2D transducer problems will be
      presented to characterize the proposed method.

PMID- 21895055
TI  - Nonlinear acoustic wave equations with fractional loss operators.
AB  - Fractional derivatives are well suited to describe wave propagation in complex
      media. When introduced in classical wave equations, they allow a modeling of
      attenuation and dispersion that better describes sound propagation in biological
      tissues. Traditional constitutive equations from solid mechanics and heat
      conduction are modified using fractional derivatives. They are used to derive a
      nonlinear wave equation which describes attenuation and dispersion laws that
      match observations. This wave equation is a generalization of the Westervelt
      equation, and also leads to a fractional version of the Khokhlov-Zabolotskaya
      Kuznetsov and Burgers' equations.

PMID- 21895056
TI  - Generalized response of a sphere embedded in a viscoelastic medium excited by an
      ultrasonic radiation force.
AB  - The response of an embedded sphere in a viscoelastic medium excited by acoustic
      radiation force has been studied in both the time- and frequency-domains. This
      model is important because it can be used to characterize the viscoelastic
      properties of the medium by fitting the response to the theoretical model. The
      Kelvin-Voigt model has been used exclusively in these models. An extension to the
      previously reported models is described so that any viscoelastic rheological
      model can be used. This theoretical development describes the generalized
      embedded sphere response both in the time and frequency domains. Comparing the
      results from derivations in both domains showed very good agreement with a median
      absolute error (MAE) ranging from 0.0044 to 0.0072. Good agreement is
      demonstrated with finite element model simulations and the theory with a MAE of
      0.006. Lastly, results for characterization of gelatin and rubber materials with
      the new theory are shown where the MAE values were used to determine which
      rheological model best describes the measured responses.

PMID- 21895057
TI  - Sound, infrasound, and sonic boom absorption by atmospheric clouds.
AB  - This study quantifies the influence of atmospheric clouds on propagation of sound
      and infrasound, based on an existing model [Gubaidulin and Nigmatulin, Int. J.
      Multiphase Flow 26, 207-228 (2000)]. Clouds are considered as a dilute and
      polydisperse suspension of liquid water droplets within a mixture of dry air and
      water vapor, both considered as perfect gases. The model is limited to low and
      medium altitude clouds, with a small ice content. Four physical mechanisms are
      taken into account: viscoinertial effects, heat transfer, water phase changes
      (evaporation and condensation), and vapor diffusion. Physical properties of
      atmospheric clouds (altitude, thickness, water content and droplet size
      distribution) are collected, along with values of the thermodynamical
      coefficients. Different types of clouds have been selected. Quantitative
      evaluation shows that, for low audible and infrasound frequencies, absorption
      within clouds is several orders of magnitude larger than classical absorption.
      The importance of phase changes and vapor diffusion is outlined. Finally,
      numerical simulations for nonlinear propagation of sonic booms indicate that, for
      thick clouds, attenuation can lead to a very large decay of the boom at the
      ground level.

PMID- 21895058
TI  - In situ calibration of atmospheric-infrasound sensors including the effects of
      wind-noise-reduction pipe systems.
AB  - A worldwide network of more than 40 infrasound monitoring stations has been
      established as part of the effort to ensure compliance with the Comprehensive
      Nuclear Test Ban Treaty. Each station has four to eight individual infrasound
      elements in a kilometer-scale array for detection and bearing determination of
      acoustic events. The frequency range of interest covers a three-decade range
      roughly from 0.01 to 10 Hz. A typical infrasound array element consists of a
      receiving transducer connected to a multiple-inlet pipe network to average
      spatially over the short-wavelength turbulence-associated "wind noise." Although
      the frequency response of the transducer itself may be known, the wind-noise
      reduction system modifies that response. In order to understand the system's
      impact on detection and identification of acoustical events, the overall
      frequency response must be determined. This paper describes a technique for
      measuring the absolute magnitude and phase of the frequency response of an
      infrasound element including the wind-noise-reduction piping by comparison
      calibration using ambient noise and a reference-microphone system. Measured
      coherence between the reference and the infrasound element and the consistency
      between the magnitude and the phase provide quality checks on the process.

PMID- 21895059
TI  - Aeroacoustic sources of motorcycle helmet noise.
AB  - The prevalence of noise in the riding of motorcycles has been a source of concern
      to both riders and researchers in recent times. Detailed flow field information
      will allow insight into the flow mechanisms responsible for the production of
      sound within motorcycle helmets. Flow field surveys of this nature are not found
      in the available literature which has tended to focus on sound pressure levels at
      ear as these are of interest for noise exposure legislation. A detailed flow
      survey of a commercial motorcycle helmet has been carried out in combination with
      surface pressure measurements and at ear acoustics. Three potential noise source
      regions are investigated, namely, the helmet wake, the surface boundary layer and
      the cavity under the helmet at the chin bar. Extensive information is provided on
      the structure of the helmet wake including its frequency content. While the wake
      and boundary layer flows showed negligible contributions to at-ear sound the
      cavity region around the chin bar was identified as a key noise source. The
      contribution of the cavity region was investigated as a function of flow speed
      and helmet angle both of which are shown to be key factors governing the sound
      produced by this region.

PMID- 21895060
TI  - Observationally constrained modeling of sound in curved ocean internal waves:
      examination of deep ducting and surface ducting at short range.
AB  - A study of 400 Hz sound focusing and ducting effects in a packet of curved
      nonlinear internal waves in shallow water is presented. Sound propagation roughly
      along the crests of the waves is simulated with a three-dimensional parabolic
      equation computational code, and the results are compared to measured propagation
      along fixed 3 and 6 km source/receiver paths. The measurements were made on the
      shelf of the South China Sea northeast of Tung-Sha Island. Construction of the
      time-varying three-dimensional sound-speed fields used in the modeling
      simulations was guided by environmental data collected concurrently with the
      acoustic data. Computed three-dimensional propagation results compare well with
      field observations. The simulations allow identification of time-dependent sound
      forward scattering and ducting processes within the curved internal gravity
      waves. Strong acoustic intensity enhancement was observed during passage of high
      amplitude nonlinear waves over the source/receiver paths, and is replicated in
      the model. The waves were typical of the region (35 m vertical displacement). Two
      types of ducting are found in the model, which occur asynchronously. One type is
      three-dimensional modal trapping in deep ducts within the wave crests (shallow
      thermocline zones). The second type is surface ducting within the wave troughs
      (deep thermocline zones).

PMID- 21895061
TI  - Acoustic inversions for measuring boundary layer suspended sediment processes.
AB  - Although sound has been applied to the study of sediment transport processes for
      a number of years, it is acknowledged that there are still problems in using the
      backscattered signal to measure suspended sediment parameters. In particular,
      when the attenuation due to the suspension becomes significant, the uncertainty
      associated with the variability in the scattering characteristics of the
      sediments in suspension can lead to inversion errors which accumulate as the
      sound propagates through the suspension. To study this attenuation propagation
      problem, numerical simulations and laboratory experiments have been used to
      assess the impact unpredictability in the scattering properties of the suspension
      has on the acoustically derived suspended sediments parameters. The results
      clearly show the commonly applied iterative implicit inversion can lead to
      calculated sediment parameters, which become increasingly erroneous with range,
      as the sound propagates through the suspension. To address this problem an
      alternative approach to the iterative implicit formulation is investigated using
      a recently described dual frequency inversion. This approach is not subject to
      the accumulation of errors and has an explicit solution. Here the dual frequency
      inversion is assessed and calculated suspended sediment parameters are compared
      with those obtained from the iterative implicit inversion.

PMID- 21895062
TI  - Effects of locally resonant modes on underwater sound absorption in viscoelastic
      materials.
AB  - Recently, by introducing locally resonant scatterers with spherical shape
      proposed in phononic crystals into design of underwater sound absorption
      materials, the low-frequency underwater sound absorption phenomenon induced by
      the localized resonances is observed. To reveal this absorption mechanism, the
      effect of the locally resonant mode on underwater sound absorption should be
      studied. In this paper, the finite element method, which is testified efficiently
      by comparing the calculation results with those of the layer multiple scattering
      method, is introduced to investigate the dynamic modes and the corresponding
      sound absorption of localized resonance. The relationship between the resonance
      modes described with the displacement contours of one unit cell and the
      corresponding absorption spectra is discussed in detail, which shows that the
      localized resonance leads to the absorption peak, and the mode conversion from
      longitudinal to transverse waves at the second absorption peak is more efficient
      than that at the first one. Finally, to show the modeling capability of FEM and
      investigate shape effects of locally resonant scatterers on underwater sound
      absorption, the absorption properties of viscoelastic materials containing
      locally resonant scatterers with ellipsoidal shape are discussed.

PMID- 21895063
TI  - Underwater Mach wave radiation from impact pile driving: theory and observation.
AB  - The underwater noise from impact pile driving is studied using a finite element
      model for the sound generation and parabolic equation model for propagation.
      Results are compared with measurements using a vertical line array deployed at a
      marine construction site in Puget Sound. It is shown that the dominant underwater
      noise from impact driving is from the Mach wave associated with the radial
      expansion of the pile that propagates down the pile after impact at supersonic
      speed. The predictions of vertical arrival angle associated with the Mach cone,
      peak pressure level as function of depth, and dominant features of the pressure
      time series compare well with corresponding field observations.

PMID- 21895064
TI  - Experimental testing of the noise-canceling processor.
AB  - Signal-processing techniques for localizing an acoustic source buried in noise
      are tested in a tank experiment. Noise is generated using a discrete source, a
      bubble generator, and a sprinkler. The experiment has essential elements of a
      realistic scenario in matched-field processing, including complex source and
      noise time series in a waveguide with water, sediment, and multipath propagation.
      The noise-canceling processor is found to outperform the Bartlett processor and
      provide the correct source range for signal-to-noise ratios below -10 dB. The
      multivalued Bartlett processor is found to outperform the Bartlett processor but
      not the noise-canceling processor.

PMID- 21895065
TI  - Resolving Lambertian surface orientation from fluctuating radiance.
AB  - A maximum likelihood method for estimating remote surface orientation from multi
      static acoustic, optical, radar, or laser images is presented. It is assumed that
      the images are corrupted by signal-dependent noise, known as speckle, arising
      from complex Gaussian field fluctuations, and that the surface properties are
      effectively Lambertian. Surface orientation estimates for a single sample are
      shown to have biases and errors that vary dramatically depending on illumination
      direction. This is due to the signal-dependent nature of speckle noise and the
      nonlinear relationship between surface orientation, illumination direction, and
      fluctuating radiance. The minimum number of independent samples necessary for
      maximum likelihood estimates to become asymptotically unbiased and to attain the
      lower bound on resolution of classical estimation theory are derived, as are
      practical design thresholds.

PMID- 21895066
TI  - Travel-time tomography in shallow water: experimental demonstration at an
      ultrasonic scale.
AB  - Acoustic tomography in a shallow ultrasonic waveguide is demonstrated at the
      laboratory scale between two source-receiver arrays. At a 1/1,000 scale, the
      waveguide represents a 1.1-km-long, 52-m-deep ocean acoustic channel in the
      kilohertz frequency range. Two coplanar arrays record the transfer matrix in the
      time domain of the waveguide between each pair of source-receiver transducers. A
      time-domain, double-beamforming algorithm is simultaneously performed on the
      source and receiver arrays that projects the multi-reflected acoustic echoes into
      an equivalent set of eigenrays, which are characterized by their travel times and
      their launch and arrival angles. Travel-time differences are measured for each
      eigenray every 0.1 s when a thermal plume is generated at a given location in the
      waveguide. Travel-time tomography inversion is then performed using two forward
      models based either on ray theory or on the diffraction-based sensitivity kernel.
      The spatially resolved range and depth inversion data confirm the feasibility of
      acoustic tomography in shallow water. Comparisons are made between inversion
      results at 1 and 3 MHz with the inversion procedure using ray theory or the
      finite-frequency approach. The influence of surface fluctuations at the air-water
      interface is shown and discussed in the framework of shallow-water ocean
      tomography.

PMID- 21895067
TI  - Information and linearity of time-domain complex demodulated amplitude and phase
      data in shallow water.
AB  - Wave-theoretic ocean acoustic propagation modeling is used to derive the
      sensitivity of pressure, and complex demodulated amplitude and phase, at a
      receiver to the sound speed of the medium using the Born-Frechet derivative.
      Although the procedure can be applied for pressure as a function of frequency
      instead of time, the time domain has advantages in practical problems, as
      linearity and signal-to-noise are more easily assigned in the time domain. The
      linearity and information content of these sensitivity kernels is explored for an
      example of a 3-4 kHz broadband pulse transmission in a 1 km shallow water Pekeris
      waveguide. Full-wave observations (pressure as a function of time) are seen to be
      too nonlinear for use in most practical cases, whereas envelope and phase data
      have a wider range of validity and provide complementary information. These
      results are used in simulated inversions with a more realistic sound speed
      profile, comparing the performance of amplitude and phase observations.

PMID- 21895068
TI  - Effects of multiple scattering, attenuation and dispersion in waveguide sensing
      of fish.
AB  - An ocean acoustic waveguide remote sensing system can instantaneously image and
      continuously monitor fish populations distributed over continental shelf-scale
      regions. Here it is shown theoretically that the areal population density of fish
      groups can be estimated from their incoherently averaged broadband matched
      filtered scattered intensities measured using a waveguide remote sensing system
      with less than 10% error. A numerical Monte-Carlo model is developed to determine
      the statistical moments of the scattered returns from a fish group. It uses the
      parabolic equation to simulate acoustic field propagation in a random range
      dependent ocean waveguide. The effects of (1) multiple scattering, (2)
      attenuation due to scattering, and (3) modal dispersion on fish population
      density imaging are examined. The model is applied to investigate population
      density imaging of shoaling Atlantic herring during the 2006 Gulf of Maine
      Experiment. Multiple scattering, attenuation and dispersion are found to be
      negligible at the imaging frequencies employed and for the herring densities
      observed. Coherent multiple scattering effects, such as resonance shifts, which
      can be significant for small highly dense fish groups on the order of the
      acoustic wavelength, are found to be negligible for the much larger groups
      typically imaged with a waveguide remote sensing system.

PMID- 21895069
TI  - Trading detection for resolution in active sonar receivers.
AB  - This paper proposes an active sonar receivers that offers a smooth trade-off
      between detection and resolution. A matched filter is the optimal detector of
      known signals in white Gaussian noise but may fail to resolve the targets if the
      time separation of targets is less than the mainlobe width of the autocorrelation
      function of the transmitted signal. An inverse filter achieves optimal resolution
      performance for multiple targets in the absence of noise, but amplifies the noise
      outside the signal bandwidth in a manner that makes it impractical in many
      realistic scenarios. The proposed active sonar receiver, the variable resolution
      and detection receiver (VRDR) combines the matched and inverse filter properties
      to achieve a smooth trade-off between detection and resolution. Simulated
      receiver operating characteristics demonstrate that for a range of dipole sonar
      targets, the performance of the VRDR is superior to the matched and inverse
      filter, as well as another previously proposed bandlimited inverse filter.

PMID- 21895070
TI  - Target time smearing with short transmissions and multipath propagation.
AB  - In active sonar the target echo level is often estimated with a propagation model
      that adds all multipath arrivals. If the (post-correlator) transmitted pulse is
      short compared to the multipath time spread then there is effectively an extra
      loss (which may be substantial) since only a few of the paths contribute to the
      target echo at any one instant. This well known "time-smearing" loss is treated
      in a self-consistent manner with previous calculations of reverberation
      [Harrison, J. Acoust. Soc. Am. 114, 2744-2756 (2003)] to estimate the target
      response and the signal-to-reverberation-ratio. Again isovelocity water,
      Lambert's law, and reflection loss proportional to angle are assumed. In this
      important short pulse regime the target response becomes independent of boundary
      reflection properties but proportional to transmitted pulse length. Thus the
      signal-to-reverberation-ratio becomes independent of pulse length. The effect on
      signal-to-ambient-noise is also investigated and the resulting formulas presented
      in a table.

PMID- 21895071
TI  - Performances of human listeners and an automatic aural classifier in
      discriminating between sonar target echoes and clutter.
AB  - Human listening tests were conducted to investigate if participants could
      distinguish between samples of target echoes and clutter obtained from a
      broadband active sonar experiment. For each echo, the listeners assigned a rating
      based on how confident they were that it was a target echo or clutter. The
      measure of performance was the area under the binormal receiver-operating
      characteristic (ROC) curve, A(z). The mean performance was A(z)=0.95 +/- 0.04
      when signals were presented with their full available acoustic bandwidth of
      approximately 0-2 kHz. It was A(z)=0.77 +/- 0.08 when the bandwidth was reduced
      to 0.5-2 kHz. The error bounds are stated as 95% confidence intervals. These
      results show that the listeners could definitely hear differences, but their
      performance was significantly degraded when the low-frequency signal information
      was removed. The performance of an automatic aural classifier was compared
      against this human-performance baseline. Results of statistical tests showed that
      it outperformed 2 of 13 listeners and 5 of 9 human listeners in the full
      bandwidth and reduced-bandwidth tests, respectively, and performed similarly to
      the other listeners. Given its performance, the automatic aural classifier may
      prove beneficial to Navy sonar systems.

PMID- 21895072
TI  - Medium characterization from interface-wave impedance and ellipticity using
      simultaneous displacement and pressure measurements.
AB  - The interface-wave impedance and ellipticity are wave attributes that interrelate
      the full waveforms as observed in different components. For each of the
      fluid/elastic-solid interface waves, i.e., the pseudo-Rayleigh (pR) and Stoneley
      (St) waves, the impedance and ellipticity are found to have different functional
      dependencies on Young's modulus and Poisson's ratio. By combining the attributes
      in a cost function, unique and stable estimates of these parameters can be
      obtained, particularly when using the St wave. In a validation experiment, the
      impedance of the laser-excited pR wave is successfully extracted from
      simultaneous measurements of the normal particle displacement and the fluid
      pressure at a water/aluminum interface. The displacement is measured using a
      laser Doppler vibrometer (LDV) and the pressure with a needle hydrophone. Any LDV
      measurement is perturbed by refractive-index changes along the LDV beam once
      acoustic waves interfere with the beam. Using a model that accounts for these
      perturbations, an impedance decrease of 28% with respect to the plane wave
      impedance of the pR wave is predicted for the water/aluminum configuration.
      Although this deviation is different for the experimentally extracted impedance,
      there is excellent agreement between the observed and predicted pR waveforms in
      both the particle displacement and fluid pressure.

PMID- 21895073
TI  - Linear frequency modulation photoacoustic radar: optimal bandwidth and signal-to
      noise ratio for frequency-domain imaging of turbid media.
AB  - The development of the pulse compression photoacoustic (PA) radar using linear
      frequency modulation (LFM) demonstrated experimentally that spectral matching of
      the signal to the ultrasonic transducer bandwidth does not necessarily produce
      the best PA signal-to-noise ratio, and it was shown that the optical and acoustic
      properties of the absorber will modify the optimal bandwidth. The effects of
      these factors are investigated in frequency-domain (FD) PA imaging by employing
      one-dimensional and axisymmetric models of the PA effect, and a Krimholtz-Leedom
      Matthaei model for the employed transducers. LFM chirps with various bandwidths
      were utilized and transducer sensitivity was measured to ensure the accuracy of
      the model. The theory was compared with experimental results and it was shown
      that the PA effect can act as a low-pass filter in the signal generation.
      Furthermore, with the PA radar, the low-frequency behavior of two-dimensional
      wave generation can appear as a false peak in the cross correlation signal trace.
      These effects are important in optimizing controllable features of the FD-PA
      method to improve image quality.

PMID- 21895074
TI  - On the acoustic radiation modes of compact regular polyhedral arrays of
      independent loudspeakers.
AB  - Compact spherical loudspeaker arrays can be used to provide control over their
      directivity pattern. Usually, this is made by adjusting the gains of
      preprogrammed spatial filters corresponding to a finite set of spherical
      harmonics, or to the acoustic radiation modes of the loudspeaker array. Unlike
      the former, the latter are closely related to the radiation efficiency of the
      source and span the subspace of the directivities it can produce. However, the
      radiation modes depend on frequency for arbitrary distributions of transducers on
      the sphere, which yields complex directivity filters. This work focuses on the
      most common loudspeaker array configurations, those following the regular shape
      of the Platonic solids. It is shown that the radiation modes of these sources are
      frequency independent, and simple algebraic expressions are derived for their
      radiation efficiencies. In addition, since such modes are vibration patterns
      driven by electrical signals, the transduction mechanism of compact multichannel
      sources is also investigated, which is an important issue, especially if the
      transducers interact inside a shared cabinet. For Platonic solid loudspeakers, it
      is shown that the common enclosure does not lead to directivity filters that
      depend on frequency.

PMID- 21895075
TI  - A hybrid approach for predicting the distribution of vibro-acoustic energy in
      complex built-up structures.
AB  - Finding the distribution of vibro-acoustic energy in complex built-up structures
      in the mid-to-high frequency regime is a difficult task. In particular,
      structures with large variation of local wavelengths and/or characteristic scales
      pose a challenge referred to as the mid-frequency problem. Standard numerical
      methods such as the finite element method (FEM) scale with the local wavelength
      and quickly become too large even for modern computer architectures. High
      frequency techniques, such as statistical energy analysis (SEA), often miss
      important information such as dominant resonance behavior due to stiff or small
      scale parts of the structure. Hybrid methods circumvent this problem by coupling
      FEM/BEM and SEA models in a given built-up structure. In the approach adopted
      here, the whole system is split into a number of subsystems that are treated by
      either FEM or SEA depending on the local wavelength. Subsystems with relative
      long wavelengths are modeled using FEM. Making a diffuse field assumption for the
      wave fields in the short wave length components, the coupling between subsystems
      can be reduced to a weighted random field correlation function. The approach
      presented results in an SEA-like set of linear equations that can be solved for
      the mean energies in the short wavelength subsystems.

PMID- 21895076
TI  - Soundscape evaluations in two critical healthcare settings with different
      designs.
AB  - Intensive care units (ICUs) have important but challenging sound environments.
      Alarms and equipment generate high levels of noise and ICUs are typically
      designed with hard surfaces. A poor sound environment can add to stress and make
      auditory tasks more difficult for clinicians. However few studies have linked
      more detailed analyses of the sound environment to nurse wellbeing and
      performance. This study is aimed at understanding the relationships between
      objective acoustic measures and self-reported nurse outcomes. Two 20-bed ICUs
      with similar patient acuity and treatment models were tested: A recently built
      neurological ICU and a 1980s-era medical-surgical ICU. The medical-surgical ICU
      was perceived as louder, more annoying, and having a greater negative impact of
      noise on work performance, health outcomes, and anxiety as compared to the
      neurological ICU. Surprisingly, there were little differences between two ICU
      sound environments based on traditional overall noise measures. The objective
      differences between the occupied sound environments in the two units only emerged
      through a more comprehensive analysis of the "occurrence rate" of peak and
      maximum levels, frequency content, and the speech interference level.
      Furthermore, mid-level transient sound occurrence rates were significantly and
      positively correlated to perceived annoyance and loudness levels.

PMID- 21895077
TI  - Multiobjective muffler shape optimization with hybrid acoustics modeling.
AB  - This paper considers the combined use of a hybrid numerical method for the
      modeling of acoustic mufflers and a genetic algorithm for multiobjective
      optimization. The hybrid numerical method provides accurate modeling of sound
      propagation in uniform waveguides with non-uniform obstructions. It is based on
      coupling a wave based modal solution in the uniform sections of the waveguide to
      a finite element solution in the non-uniform component. Finite element method
      provides flexible modeling of complicated geometries, varying material
      parameters, and boundary conditions, while the wave based solution leads to
      accurate treatment of non-reflecting boundaries and straightforward computation
      of the transmission loss (TL) of the muffler. The goal of optimization is to
      maximize TL at multiple frequency ranges simultaneously by adjusting chosen shape
      parameters of the muffler. This task is formulated as a multiobjective
      optimization problem with the objectives depending on the solution of the
      simulation model. NSGA-II genetic algorithm is used for solving the
      multiobjective optimization problem. Genetic algorithms can be easily combined
      with different simulation methods, and they are not sensitive to the smoothness
      properties of the objective functions. Numerical experiments demonstrate the
      accuracy and feasibility of the model-based optimization method in muffler
      design.

PMID- 21895078
TI  - Generalized acoustic energy density.
AB  - The properties of acoustic kinetic energy density and total energy density of
      sound fields in lightly damped enclosures have been explored thoroughly in the
      literature. Their increased spatial uniformity makes them more favorable
      measurement quantities for various applications than acoustic potential energy
      density (or squared pressure), which is most often used. In this paper, a
      generalized acoustic energy density (GED), will be introduced. It is defined by
      introducing weighting factors into the formulation of total acoustic energy
      density. With an additional degree of freedom, the GED can conform to the
      traditional acoustic energy density quantities, or it can be optimized for
      different applications. The properties of the GED will be explored in this paper
      for individual room modes, a diffuse sound field, and a sound field below the
      Schroeder frequency.

PMID- 21895079
TI  - Numerical evidence of mixing in rooms using the free path temporal distribution.
AB  - The ergodic propriety of a room has strong effects on its reverberation. If the
      room is ergodic, the reverberation can be broken up in two steps: a deterministic
      process followed by a stochastic one. The late reverberation can be then modeled
      by a reverberation algorithm instead of more computationally consuming methods.
      In this study, the free path temporal distribution obtained by ray-tracing is
      used as an indicator of the room's mixing: the energetic average of the path
      lengths is computed at each time step. Ergodic rooms are thus characterized by
      rapidly convergent distributions. The free path value becomes independent of
      time. On the other hand, path selection mechanism and orbits are observed in non
      ergodic rooms. The transition time from the deterministic process to the
      stochastic one is also studied through the evaluation of the room's time
      constant. It is shown that its value depends only on the mean free path and the
      boundaries scattering value. An empirical expression is obtained which agrees
      well with simulations carried out in a concert hall. This transition time from a
      deterministic model to a stochastic one can be used to speed up the acoustical
      predictions and auralizations in ergodic rooms.

PMID- 21895080
TI  - Propagation of acoustic waves in a one-dimensional macroscopically inhomogeneous
      poroelastic material.
AB  - Wave propagation in macroscopically inhomogeneous porous materials has received
      much attention in recent years. The wave equation, derived from the alternative
      formulation of Biot's theory of 1962, was reduced and solved recently in the case
      of rigid frame inhomogeneous porous materials. This paper focuses on the solution
      of the full wave equation in which the acoustic and the elastic properties of the
      poroelastic material vary in one-dimension. The reflection coefficient of a one
      dimensional macroscopically inhomogeneous porous material on a rigid backing is
      obtained numerically using the state vector (or the so-called Stroh) formalism
      and Peano series. This coefficient can then be used to straightforwardly
      calculate the scattered field. To validate the method of resolution, results
      obtained by the present method are compared to those calculated by the classical
      transfer matrix method at both normal and oblique incidence and to experimental
      measurements at normal incidence for a known two-layers porous material,
      considered as a single inhomogeneous layer. Finally, discussion about the
      absorption coefficient for various inhomogeneity profiles gives further
      perspectives.

PMID- 21895081
TI  - A survey of acoustic conditions in semi-open plan classrooms in the United
      Kingdom.
AB  - This paper reports the results of a large scale, detailed acoustic survey of 42
      open plan classrooms of varying design in the UK each of which contained between
      2 and 14 teaching areas or classbases. The objective survey procedure, which was
      designed specifically for use in open plan classrooms, is described. The acoustic
      measurements relating to speech intelligibility within a classbase, including
      ambient noise level, intrusive noise level, speech to noise ratio, speech
      transmission index, and reverberation time, are presented. The effects on speech
      intelligibility of critical physical design variables, such as the number of
      classbases within an open plan unit and the selection of acoustic finishes for
      control of reverberation, are examined. This analysis enables limitations of open
      plan classrooms to be discussed and acoustic design guidelines to be developed to
      ensure good listening conditions. The types of teaching activity to provide
      adequate acoustic conditions, plus the speech intelligibility requirements of
      younger children, are also discussed.

PMID- 21895082
TI  - Acceptable range of speech level in noisy sound fields for young adults and
      elderly persons.
AB  - The acceptable range of speech level as a function of background noise level was
      investigated on the basis of word intelligibility scores and listening difficulty
      ratings. In the present study, the acceptable range is defined as the range that
      maximizes word intelligibility scores and simultaneously does not cause a
      significant increase in listening difficulty ratings from the minimum ratings.
      Listening tests with young adult and elderly listeners demonstrated the
      following. (1) The acceptable range of speech level for elderly listeners
      overlapped that for young listeners. (2) The lower limit of the acceptable speech
      level for both young and elderly listeners was 65 dB (A-weighted) for noise
      levels of 40 and 45 dB (A-weighted), a level with a speech-to-noise ratio of +15
      dB for noise levels of 50 and 55 dB, and a level with a speech-to-noise ratio of
      +10 dB for noise levels from 60 to 70 dB. (3) The upper limit of the acceptable
      speech level for both young and elderly listeners was 80 dB for noise levels from
      40 to 55 dB and 85 dB or above for noise levels from 55 to 70 dB.

PMID- 21895083
TI  - Dynamical energy analysis for built-up acoustic systems at high frequencies.
AB  - Standard methods for describing the intensity distribution of mechanical and
      acoustic wave fields in the high frequency asymptotic limit are often based on
      flow transport equations. Common techniques are statistical energy analysis,
      employed mostly in the context of vibro-acoustics, and ray tracing, a popular
      tool in architectural acoustics. Dynamical energy analysis makes it possible to
      interpolate between standard statistical energy analysis and full ray tracing,
      containing both of these methods as limiting cases. In this work a version of
      dynamical energy analysis based on a Chebyshev basis expansion of the Perron
      Frobenius operator governing the ray dynamics is introduced. It is shown that the
      technique can efficiently deal with multi-component systems overcoming typical
      geometrical limitations present in statistical energy analysis. Results are
      compared with state-of-the-art hp-adaptive discontinuous Galerkin finite element
      simulations.

PMID- 21895084
TI  - Transient nearfield acoustic holography based on an interpolated time-domain
      equivalent source method.
AB  - Transient nearfield acoustic holography based on an interpolated time-domain
      equivalent source method (ESM) is proposed to reconstruct transient acoustic
      fields directly in the time domain. Since the equivalent source strengths solved
      by the traditional time-domain ESM formulation cannot be used to reconstruct the
      pressure on the source surface directly, an interpolation function is introduced
      to develop an interpolated time-domain ESM formulation which permits one to
      deduce an iterative reconstruction process. As the reconstruction process is ill
      conditioned and especially there exists a cumulative effect of errors, the
      Tikhonov regularization is used to stabilize the process. Numerical examples of
      reconstructing transient acoustic fields from a baffled planar piston, an
      impulsively accelerating sphere and a cube box, respectively, demonstrate that
      the proposed method not only can effectively reconstruct transient acoustic
      fields in the time domain, but also can visualize acoustic fields in the space
      domain. And, in the first numerical example, the cumulative effect of errors and
      the validity of using the Tikhonov regularization to suppress the errors are
      described.

PMID- 21895085
TI  - Fluid coupling in a discrete model of cochlear mechanics.
AB  - A discrete model of cochlear mechanics is introduced that includes a full, three
      dimensional, description of fluid coupling. This formulation allows the fluid
      coupling and basilar membrane dynamics to be analyzed separately and then coupled
      together with a simple piece of linear algebra. The fluid coupling is initially
      analyzed using a wavenumber formulation and is separated into one component due
      to one-dimensional fluid coupling and one comprising all the other contributions.
      Using the theory of acoustic waves in a duct, however, these two components of
      the pressure can also be associated with a far field, due to the plane wave, and
      a near field, due to the evanescent, higher order, modes. The near field
      components are then seen as one of a number of sources of additional longitudinal
      coupling in the cochlea. The effects of non-uniformity and asymmetry in the fluid
      chamber areas can also be taken into account, to predict both the pressure
      difference between the chambers and the mean pressure. This allows the
      calculation, for example, of the effect of a short cochlear implant on the
      coupled response of the cochlea.

PMID- 21895086
TI  - Modeling the eardrum as a string with distributed force.
AB  - In this paper, an analytical model of the tympanic membrane is introduced where
      the two-dimensional tympanic membrane is reduced to a one-dimensional string. It
      is intended to bridge the gap between lumped-element models and finite-element
      models. In contrast to known lumped-element models, the model takes the
      distributed effect of the sound field on the tympanic membrane into account.
      Compared to finite-element models, it retains the advantage of a low number of
      parameters. The model is adjusted to forward and reverse transfer functions of
      the guinea-pig middle ear. Although the fitting to experimental data is not
      perfect, important conclusions can be drawn. For instance, the model shows that
      the delay of surface waves on the tympanic membrane can be different from the
      signal transmission delay of the tympanic membrane. In a similar vein, the
      standing wave ratio on the tympanic membrane and within the ear canal can
      considerably differ. Further, the model shows that even in a low-loss tympanic
      membrane the effective area, which commonly is associated with the transformer
      ratio in a lumped-element and some hybrid circuit models, not only is frequency
      dependent, but also different for forward and reverse transduction.

PMID- 21895087
TI  - A cocktail party model of spatial release from masking by both noise and speech
      interferers.
AB  - A mathematical formula for estimating spatial release from masking (SRM) in a
      cocktail party environment would be useful as a simpler alternative to
      computationally intensive algorithms and may enhance understanding of underlying
      mechanisms. The experiment presented herein was designed to provide a strong test
      of a model that divides SRM into contributions of asymmetry and angular
      separation [Bronkhorst (2000). Acustica 86, 117-128] and to examine whether that
      model can be extended to include speech maskers. Across masker types the
      contribution to SRM of angular separation of maskers from the target was found to
      grow at a diminishing rate as angular separation increased within the frontal
      hemifield, contrary to predictions of the model. Speech maskers differed from
      noise maskers in the overall magnitude of SRM and in the contribution of angular
      separation (both greater for speech). These results were used to develop a
      modified model that achieved good fits to data for noise maskers (rho=0.93) and
      for speech maskers (rho=0.94) while using the same functions to describe
      separation and asymmetry components of SRM for both masker types. These findings
      suggest that this approach can be used to accurately model SRM for speech maskers
      in addition to primarily "energetic" noise maskers.

PMID- 21895088
TI  - Predicting speech intelligibility based on the signal-to-noise envelope power
      ratio after modulation-frequency selective processing.
AB  - A model for predicting the intelligibility of processed noisy speech is proposed.
      The speech-based envelope power spectrum model has a similar structure as the
      model of Ewert and Dau [(2000). J. Acoust. Soc. Am. 108, 1181-1196], developed to
      account for modulation detection and masking data. The model estimates the speech
      to-noise envelope power ratio, SNR(env), at the output of a modulation filterbank
      and relates this metric to speech intelligibility using the concept of an ideal
      observer. Predictions were compared to data on the intelligibility of speech
      presented in stationary speech-shaped noise. The model was further tested in
      conditions with noisy speech subjected to reverberation and spectral subtraction.
      Good agreement between predictions and data was found in all cases. For spectral
      subtraction, an analysis of the model's internal representation of the stimuli
      revealed that the predicted decrease of intelligibility was caused by the
      estimated noise envelope power exceeding that of the speech. The classical
      concept of the speech transmission index fails in this condition. The results
      strongly suggest that the signal-to-noise ratio at the output of a modulation
      frequency selective process provides a key measure of speech intelligibility.

PMID- 21895089
TI  - Auditory-nerve responses predict pitch attributes related to musical consonance
      dissonance for normal and impaired hearing.
AB  - Human listeners prefer consonant over dissonant musical intervals and the
      perceived contrast between these classes is reduced with cochlear hearing loss.
      Population-level activity of normal and impaired model auditory-nerve (AN) fibers
      was examined to determine (1) if peripheral auditory neurons exhibit correlates
      of consonance and dissonance and (2) if the reduced perceptual difference between
      these qualities observed for hearing-impaired listeners can be explained by
      impaired AN responses. In addition, acoustical correlates of consonance
      dissonance were also explored including periodicity and roughness. Among the
      chromatic pitch combinations of music, consonant intervals/chords yielded more
      robust neural pitch-salience magnitudes (determined by harmonicity/periodicity)
      than dissonant intervals/chords. In addition, AN pitch-salience magnitudes
      correctly predicted the ordering of hierarchical pitch and chordal sonorities
      described by Western music theory. Cochlear hearing impairment compressed pitch
      salience estimates between consonant and dissonant pitch relationships. The
      reduction in contrast of neural responses following cochlear hearing loss may
      explain the inability of hearing-impaired listeners to distinguish musical qualia
      as clearly as normal-hearing individuals. Of the neural and acoustic correlates
      explored, AN pitch salience was the best predictor of behavioral data. Results
      ultimately show that basic pitch relationships governing music are already
      present in initial stages of neural processing at the AN level.

PMID- 21895090
TI  - Perceived tonal continuity through two noise bursts separated by silence.
AB  - Three experiments measured the perceived continuity of two pure tones "flankers"
      through a masker containing a silence. Experiment 1 used a 2I-2AFC procedure; one
      interval contained two noise bursts separated by a silent gap, and the other
      contained two noise bursts separated by a tone of the same duration as the
      silence. Discrimination between masker conditions was very accurate when the
      flankers were absent but was impaired substantially when the flankers were
      present. This was taken as evidence that illusory flanker continuity during the
      silent gap was heard as similar to the physical presence of a tone in the gap. In
      experiment 2, performance remained poor when the flankers were frequency glides
      aligned along a common trajectory. Performance improved significantly when the
      flankers were misaligned in trajectory. In experiment 3, listeners rated directly
      perceived flanker continuity. Strong continuity was reported in the silent gap
      conditions for which poor performance had been observed in experiments 1 and 2.
      These findings show that continuity may be heard through a masker that cannot
      mask a physically continuous tone but can mask the flankers' offset and onset.
      The results are explained in terms of the perceptual grouping of onsets and
      offsets of the flankers.

PMID- 21895091
TI  - Effects of envelope shape on interaural envelope delay sensitivity in acoustic
      and electric hearing.
AB  - The envelope shape is important for the perception of interaural time difference
      (ITD) in the envelope as supported by the improved sensitivity for transposed
      tones compared to sinusoidally amplitude-modulated (SAM) tones. The present study
      investigated the effects of specific envelope parameters in nine normal-hearing
      (NH) and seven cochlear-implant (CI) listeners, using high-rate carriers with 27
      Hz trapezoidal modulation. In NH listeners, increasing the off time (the silent
      interval in each modulation cycle) up to 12 ms, increasing the envelope slope
      from 6 to 8 dB/ms, and increasing the peak level improved ITD sensitivity. The
      combined effect of the off time and slope accounts for the gain in sensitivity
      for transposed tones relative to SAM tones. In CI listeners, increasing the off
      time up to 20 ms improved sensitivity, but increasing the slope showed no
      systematic effect. A 27-pulses/s electric pulse train, representing a special
      case of modulation with infinitely steep slopes and maximum possible off time,
      yielded considerably higher sensitivity compared to the best condition with
      trapezoidal modulation. Overall, the results of this study indicate that envelope
      ITD sensitivity could be improved by using CI processing schemes that
      simultaneously increase the off time and the peak level of the signal envelope.

PMID- 21895092
TI  - Effect of stimulus spectrum on distance perception for nearby sources.
AB  - The effects of stimulus frequency and bandwidth on distance perception were
      examined for nearby sources in simulated reverberant space. Sources to the side
      [containing reverberation-related cues and interaural level difference (ILD)
      cues] and to the front (without ILDs) were simulated. Listeners judged the
      distance of noise bursts presented at a randomly roving level from simulated
      distances ranging from 0.15 to 1.7 m. Six stimuli were tested, varying in center
      frequency (300-5700 Hz) and bandwidth (200-5400 Hz). Performance, measured as the
      correlation between simulated and response distances, was worse for frontal than
      for lateral sources. For both simulated directions, performance was inversely
      proportional to the low-frequency stimulus cutoff, independent of stimulus
      bandwidth. The dependence of performance on frequency was stronger for frontal
      sources. These correlation results were well summarized by considering how mean
      response, as opposed to response variance, changed with stimulus direction and
      spectrum: (1) little bias was observed for lateral sources, but listeners
      consistently overestimated distance for frontal nearby sources; (2) for both
      directions, increasing the low-frequency cut-off reduced the range of responses.
      These results are consistent with the hypothesis that listeners used a direction
      independent but frequency-dependent mapping of a reverberation-related cue, not
      the ILD cue, to judge source distance.

PMID- 21895093
TI  - Can basic auditory and cognitive measures predict hearing-impaired listeners'
      localization and spatial speech recognition abilities?
AB  - This study aimed to clarify the basic auditory and cognitive processes that
      affect listeners' performance on two spatial listening tasks: sound localization
      and speech recognition in spatially complex, multi-talker situations. Twenty
      three elderly listeners with mild-to-moderate sensorineural hearing impairments
      were tested on the two spatial listening tasks, a measure of monaural spectral
      ripple discrimination, a measure of binaural temporal fine structure (TFS)
      sensitivity, and two (visual) cognitive measures indexing working memory and
      attention. All auditory test stimuli were spectrally shaped to restore (partial)
      audibility for each listener on each listening task. Eight younger normal-hearing
      listeners served as a control group. Data analyses revealed that the chosen
      auditory and cognitive measures could predict neither sound localization accuracy
      nor speech recognition when the target and maskers were separated along the front
      back dimension. When the competing talkers were separated along the left-right
      dimension, however, speech recognition performance was significantly correlated
      with the attentional measure. Furthermore, supplementary analyses indicated
      additional effects of binaural TFS sensitivity and average low-frequency hearing
      thresholds. Altogether, these results are in support of the notion that both
      bottom-up and top-down deficits are responsible for the impaired functioning of
      elderly hearing-impaired listeners in cocktail party-like situations.

PMID- 21895094
TI  - Discrimination between sequential and simultaneous virtual channels with
      electrical hearing.
AB  - In cochlear implants (CIs), simultaneous or sequential stimulation of adjacent
      electrodes can produce intermediate pitch percepts between those of the component
      electrodes. However, it is unclear whether simultaneous and sequential virtual
      channels (VCs) can be discriminated. In this study, CI users were asked to
      discriminate simultaneous and sequential VCs; discrimination was measured for
      monopolar (MP) and bipolar + 1 stimulation (BP + 1), i.e., relatively broad and
      focused stimulation modes. For sequential VCs, the interpulse interval (IPI)
      varied between 0.0 and 1.8 ms. All stimuli were presented at comfortably loud,
      loudness-balanced levels at a 250 pulse per second per electrode (ppse)
      stimulation rate. On average, CI subjects were able to reliably discriminate
      between sequential and simultaneous VCs. While there was no significant effect of
      IPI or stimulation mode on VC discrimination, some subjects exhibited better VC
      discrimination with BP + 1 stimulation. Subjects' discrimination between
      sequential and simultaneous VCs was correlated with electrode discrimination,
      suggesting that spatial selectivity may influence perception of sequential VCs.
      To maintain equal loudness, sequential VC amplitudes were nearly double those of
      simultaneous VCs, presumably resulting in a broader spread of excitation. These
      results suggest that perceptual differences between simultaneous and sequential
      VCs might be explained by differences in the spread of excitation.

PMID- 21895095
TI  - Detection and rate discrimination of amplitude modulation in electrical hearing.
AB  - Three experiments were designed to examine temporal envelope processing by
      cochlear implant (CI) listeners. In experiment 1, the hypothesis that listeners'
      modulation sensitivity would in part determine their ability to discriminate
      between temporal modulation rates was examined. Temporal modulation transfer
      functions (TMTFs) obtained in an amplitude modulation detection (AMD) task were
      compared to threshold functions obtained in an amplitude modulation rate
      discrimination (AMRD) task. Statistically significant nonlinear correlations were
      observed between the two measures. In experiment 2, results of loudness-balancing
      showed small increases in the loudness of modulated over unmodulated stimuli
      beyond a modulation depth of 16%. Results of experiment 3 indicated small but
      statistically significant effects of level-roving on the overall gain of the
      TMTF, but no impact of level-roving on the average shape of the TMTF across
      subjects. This suggested that level-roving simply increased the task difficulty
      for most listeners, but did not indicate increased use of intensity cues under
      more challenging conditions. Data obtained with one subject, however, suggested
      that the most sensitive listeners may derive some benefit from intensity cues in
      these tasks. Overall, results indicated that intensity cues did not play an
      important role in temporal envelope processing by the average CI listener.

PMID- 21895096
TI  - Gain-induced speech distortions and the absence of intelligibility benefit with
      existing noise-reduction algorithms.
AB  - Most noise-reduction algorithms used in hearing aids apply a gain to the noisy
      envelopes to reduce noise interference. The present study assesses the impact of
      two types of speech distortion introduced by noise-suppressive gain functions:
      amplification distortion occurring when the amplitude of the target signal is
      over-estimated, and attenuation distortion occurring when the target amplitude is
      under-estimated. Sentences corrupted by steady noise and competing talker were
      processed through a noise-reduction algorithm and synthesized to contain either
      amplification distortion, attenuation distortion or both. The attenuation
      distortion was found to have a minimal effect on speech intelligibility. In fact,
      substantial improvements (>80 percentage points) in intelligibility, relative to
      noise-corrupted speech, were obtained when the processed sentences contained only
      attenuation distortion. When the amplification distortion was limited to be
      smaller than 6 dB, performance was nearly unaffected in the steady-noise
      conditions, but was severely degraded in the competing-talker conditions.
      Overall, the present data suggest that one reason that existing algorithms do not
      improve speech intelligibility is because they allow amplification distortions in
      excess of 6 dB. These distortions are shown in this study to be always associated
      with masker-dominated envelopes and should thus be eliminated.

PMID- 21895097
TI  - Phonation threshold pressure: comparison of calculations and measurements taken
      with physical models of the vocal fold mucosa.
AB  - In an important paper on the physics of small amplitude oscillations, Titze
      showed that the essence of the vertical phase difference, which allows energy to
      be transferred from the flowing air to the motion of the vocal folds, could be
      captured in a surface wave model, and he derived a formula for the phonation
      threshold pressure with an explicit dependence on the geometrical and
      biomechanical properties of the vocal folds. The formula inspired a series of
      experiments [e.g., R. Chan and I. Titze, J. Acoust. Soc. Am 119, 2351-2362
      (2006)]. Although the experiments support many aspects of Titze's formula,
      including a linear dependence on the glottal half-width, the behavior of the
      experiments at the smallest values of this parameter is not consistent with the
      formula. It is shown that a key element for removing this discrepancy lies in a
      careful examination of the properties of the entrance loss coefficient. In
      particular, measurements of the entrance loss coefficient at small widths done
      with a physical model of the glottis (M5) show that this coefficient varies
      inversely with the glottal width. A numerical solution of the time-dependent
      equations of the surface wave model shows that adding a supraglottal vocal tract
      lowers the phonation threshold pressure by an amount approximately consistent
      with Chan and Titze's experiments.

PMID- 21895098
TI  - Phonetic variability of stops and flaps in spontaneous and careful speech.
AB  - Variability is perhaps the most notable characteristic of speech, and it is
      particularly noticeable in spontaneous conversational speech. The current
      research examines how speakers realize the American English stops /p, k, b, g/
      and flaps (r from /t, d/), in casual conversation and in careful speech. Target
      consonants appear after stressed syllables (e.g., "lobby") or between unstressed
      syllables (e.g., "humanity"), in one of six segmental/word-boundary environments.
      This work documents the degree and types of variability listeners encounter and
      must parse. Findings show greater reduction in connected and spontaneous speech,
      greater reduction in high frequency phrases (but not within high frequency
      words), and greater reduction between unstressed syllables than after a stress.
      Although highly reduced productions of stops and flaps occur often, with
      approximant-like tokens even in careful speech, reduction does not lead to a
      large amount of overlap between phonological categories. Approximant-like
      realizations of expected stops and flaps in some conditions constitute the
      majority of tokens. This shows that reduced speech is something that listeners
      encounter, and must perceive, in a large proportion of the speech they hear.

PMID- 21895099
TI  - Verification of two minimally invasive methods for the estimation of the contact
      pressure in human vocal folds during phonation.
AB  - The contact pressure on the vocal fold surface during high pitch or amplitude
      voice production is believed to be one major source of phonotrauma. Models for
      the quantitative estimate of the contact pressure may be valuable for prevention
      and treatment. Various indirect and minimally invasive approaches have been
      purported to estimate contact pressure. But the accuracy of these methods has not
      yet been objectively verified in controlled laboratory settings. In the present
      study, two indirect approaches for the estimation of the contact pressure were
      investigated. One is based on a Hertzian impact model, and the other on a finite
      element model. A probe microphone was used for direct measurements of the contact
      pressure and verifications of the indirect approaches. A silicone replica of
      human vocal folds was used as a test bed. Consistent contact pressure estimations
      were obtained using all three methods. The advantages and disadvantages of each
      approach for eventual clinical applications are described.

PMID- 21895100
TI  - Formant onsets and formant transitions as developmental cues to vowel perception.
AB  - The purpose of this study was to determine whether children give more perceptual
      weight than do adults to dynamic spectral cues versus static cues. Listeners were
      10 children between the ages of 3;8 and 4;1 (mean 3;11) and ten adults between
      the ages of 23;10 and 32;0 (mean 25;11). Three experimental stimulus conditions
      were presented, with each containing stimuli of 30 ms duration. The first
      experimental condition consisted of unchanging formant onset frequencies ranging
      in value from frequencies for [i] to those for [a], appropriate for a bilabial
      stop consonant context. The second two experimental conditions consisted of
      either an [i] or [a] onset frequency with a 25 ms portion of a formant transition
      whose trajectory was toward one of a series of target frequencies ranging from
      those for [i] to those for [a]. Results indicated that the children attended
      differently than the adults on both the [a] and [i] formant onset frequency cue
      to identify the vowels. The adults gave more equal weight to the [i]-onset and
      [a]-onset dynamic cues as reflected in category boundaries than the children did.
      For the [i]-onset condition, children were not as confident compared to adults in
      vowel perception, as reflected in slope analyses.

PMID- 21895101
TI  - Perception of intrusive /r/ in English by native, cross-language and cross
      dialect listeners.
AB  - In sequences such as law and order, speakers of British English often insert /r/
      between law and and. Acoustic analyses revealed such "intrusive" /r/ to be
      significantly shorter than canonical /r/. In a 2AFC experiment, native listeners
      heard British English sentences in which /r/ duration was manipulated across a
      word boundary [e.g., saw (r)ice], and orthographic and semantic factors were
      varied. These listeners responded categorically on the basis of acoustic evidence
      for /r/ alone, reporting ice after short /r/s, rice after long /r/s; orthographic
      and semantic factors had no effect. Dutch listeners proficient in English who
      heard the same materials relied less on durational cues than the native
      listeners, and were affected by both orthography and semantic bias. American
      English listeners produced intermediate responses to the same materials, being
      sensitive to duration (less so than native, more so than Dutch listeners), and to
      orthography (less so than the Dutch), but insensitive to the semantic
      manipulation. Listeners from language communities without common use of intrusive
      /r/ may thus interpret intrusive /r/ as canonical /r/, with a language difference
      increasing this propensity more than a dialect difference. Native listeners,
      however, efficiently distinguish intrusive from canonical /r/ by exploiting the
      relevant acoustic variation.

PMID- 21895102
TI  - Second-language experience and speech-in-noise recognition: effects of talker
      listener accent similarity.
AB  - Previous work has shown that the intelligibility of speech in noise is degraded
      if the speaker and listener differ in accent, in particular when there is a
      disparity between native (L1) and nonnative (L2) accents. This study investigated
      how this talker-listener interaction is modulated by L2 experience and accent
      similarity. L1 Southern British English, L1 French listeners with varying L2
      English experience, and French-English bilinguals were tested on the recognition
      of English sentences mixed in speech-shaped noise that was spoken with a range of
      accents (French, Korean, Northern Irish, and Southern British English). The
      results demonstrated clear interactions of accent and experience, with the least
      experienced French speakers being most accurate with French-accented English, but
      more experienced listeners being most accurate with L1 Southern British English
      accents. An acoustic similarity metric was applied to the speech productions of
      the talkers and the listeners, and significant correlations were obtained between
      accent similarity and sentence intelligibility for pairs of individuals. Overall,
      the results suggest that L2 experience affects talker-listener accent
      interactions, altering both the intelligibility of different accents and the
      selectivity of accent processing.

PMID- 21895103
TI  - Sizing up the competition: quantifying the influence of the mental lexicon on
      auditory and visual spoken word recognition.
AB  - Much research has explored how spoken word recognition is influenced by the
      architecture and dynamics of the mental lexicon (e.g., Luce and Pisoni, 1998;
      McClelland and Elman, 1986). A more recent question is whether the processes
      underlying word recognition are unique to the auditory domain, or whether
      visually perceived (lipread) speech may also be sensitive to the structure of the
      mental lexicon (Auer, 2002; Mattys, Bernstein, and Auer, 2002). The current
      research was designed to test the hypothesis that both aurally and visually
      perceived spoken words are isolated in the mental lexicon as a function of their
      modality-specific perceptual similarity to other words. Lexical competition (the
      extent to which perceptually similar words influence recognition of a stimulus
      word) was quantified using metrics that are well-established in the literature,
      as well as a statistical method for calculating perceptual confusability based on
      the phi-square statistic. Both auditory and visual spoken word recognition were
      influenced by modality-specific lexical competition as well as stimulus word
      frequency. These findings extend the scope of activation-competition models of
      spoken word recognition and reinforce the hypothesis (Auer, 2002; Mattys et al.,
      2002) that perceptual and cognitive properties underlying spoken word recognition
      are not specific to the auditory domain. In addition, the results support the use
      of the phi-square statistic as a better predictor of lexical competition than
      metrics currently used in models of spoken word recognition.

PMID- 21895104
TI  - Acoustic analysis and mood classification of pain-relieving music.
AB  - Listening to preferred music (that which is chosen by the participant) has been
      shown to be effective in mitigating the effects of pain when compared to silence
      and a variety of distraction techniques. The wide range of genre, tempo, and
      structure in music chosen by participants in studies utilizing experimentally
      induced pain has led to the assertion that structure does not play a significant
      role, rather listening to preferred music renders the music "functionally
      equivalent" as regards its effect upon pain perception. This study addresses this
      assumption and performs detailed analysis of a selection of music chosen from
      three pain studies. Music analysis showed significant correlation between timbral
      and tonal aspects of music and measurements of pain tolerance and perceived pain
      intensity. Mood classification was performed using a hierarchical Gaussian
      Mixture Model, which indicated the majority of the chosen music expressed
      contentment. The results suggest that in addition to personal preference,
      associations with music and the listening context, emotion expressed by music, as
      defined by its acoustical content, is important to enhancing emotional engagement
      with music and therefore enhances the level of pain reduction and tolerance.

PMID- 21895105
TI  - Vibrato rate and extent in soprano voice: a survey on one century of singing.
AB  - This work presents a statistical study of vibrato parameters in soprano voices.
      More than one hundred recordings of the same tone sung by 75 artists have been
      analyzed. Vibrato rate and extent, tone length and intonation, together with
      their correlations are the main parameters under examination. The study shows a
      clear decrease of the mean vibrato rate during the last century (-1.8+/-0.3
      Hz/century), together with an increase of vibrato extent (56.4+/
      0.3cent/century). Vibrato rate and extent show a statistically significant
      negative correlation (r=-0.62). Vibrato rate increase near the end of the tone
      has been observed too, in agreement with previous measurements, together with a
      mean increase of the pitch of the tone. A small positive correlation has been
      also found among note duration and vibrato extent.

PMID- 21895106
TI  - Reconstruction of the signal produced by a directional sound source from remote
      multi-microphone recordings.
AB  - A mathematical method for reconstructing the signal produced by a directional
      sound source from knowledge of the same signal in the far field, i.e., microphone
      recordings, is developed. The key idea is to compute inverse filters that
      compensate for the directional filtering of the signal by the sound source
      directivity, using a least-square error optimization strategy. Previous work
      pointed out how the method strongly depends on arrival times of signal in the
      microphone recordings. Two strategies are used in this paper for calculating the
      time shifts that are afterward taken as inputs, together with source directivity,
      for the reconstruction. The method has been tested in a laboratory environment,
      where ground truth was available, with a Polaroid transducer as source. The
      reconstructions are similar with both strategies. The performance of the method
      also depends on source orientation.

PMID- 21895107
TI  - Vocal cues indicate level of arousal in infant African elephant roars.
AB  - Arousal-based physiological changes influence acoustic features of vocalizations
      in mammals. In particular, nonlinear phenomena are thought to convey information
      about the caller's arousal state. This hypothesis was tested in the infant
      African elephant (Loxodonta africana) roar, a call type produced in situations of
      arousal and distress. Ninety-two percent of roars exhibited nonlinear phenomena,
      with chaos being the most common type. Acoustic irregularities were strongly
      associated with elevated fundamental frequency values. Roars produced in
      situations of highest urgency, based on the occurrence of behavioral indicators
      of arousal, were characterized by the lowest harmonics-to-noise ratio; this
      indicates low tonality. In addition, roars produced in these situations lasted
      longer than those produced in contexts of lower presumed urgency. Testing the
      infant roars for individual distinctiveness revealed only a moderate
      classification result. Combined, these findings indicate that infant African
      elephant roars primarily function to signal the caller's arousal state. The
      effective communication of this type of information may allow mothers to respond
      differentially based on their infant's degree of need and may be crucial for the
      survival of infant African elephants in their natural environment.

PMID- 21895108
TI  - Interaction of emitted sonar pulses and simulated echoes in a false killer whale:
      an evoked-potential study.
AB  - Auditory evoked potentials (AEP) were recorded during echolocation in a false
      killer whale Pseudorca crassidens. An electronically synthesized and played-back
      (simulated) echo was triggered by an emitted biosonar pulse, and its intensity
      was proportional to that of the emitted click. The delay and transfer factor of
      the echo relative to the emitted click was controlled by the operator. The echo
      delay varied from 2 to 16 ms (by two-fold steps), and the transfer factor varied
      within ranges from -45 to -30 dB at the 2-ms delay to -60 to -45 dB at the 16-ms
      delay. Echo-related AEPs featured amplitude dependence both on echo delay at a
      constant transfer factor (the longer the delay, the higher amplitude) and on echo
      transfer factor at a constant delay (the higher transfer factor, the higher
      amplitude). Conjunctional variation of the echo transfer factor and delay kept
      the AEP amplitude constant when the delay to transfer factor trade was from -7.1
      to -8.4 dB per delay doubling. The results confirm the hypothesis that partial
      forward masking of the echoes by the preceding emitted sonar pulses serves as a
      time-varying automatic gain control in the auditory system of echolocating
      odontocetes.

PMID- 21895109
TI  - High-resolution imaging without iteration: a fast and robust method for breast
      ultrasound tomography.
AB  - Breast ultrasound tomography has the potential to improve the cost, safety, and
      reliability of breast cancer screening and diagnosis over the gold-standard of
      mammography. Vital to achieving this potential is the development of imaging
      algorithms to unravel the complex anatomy of the breast and its mechanical
      properties. The solution most commonly relied upon is time-of-flight tomography,
      but this exhibits low resolution due to the presence of diffraction effects.
      Iterative full-wave inversion methods present one solution to achieve higher
      resolution, but these are slow and are not guaranteed to converge to the correct
      solution. Presented here is HARBUT, the hybrid algorithm for robust breast
      ultrasound tomography, which utilizes the complementary strengths of time-of
      flight and diffraction tomography resulting in a direct, fast, robust and
      accurate high resolution method of reconstructing the sound speed through the
      breast. The algorithm is shown to produce accurate reconstructions with realistic
      data from a complex three-dimensional simulation, with masses as small as 4 mm
      being clearly visible.

PMID- 21895147
TI  - Communication: uncovering molecule-TiO2 interactions with nonlinear spectroscopy.
AB  - Femtosecond transient grating experiments are used to investigate electronic
      structures and transport mechanisms in dye-sensitized nanocrystalline TiO(2)
      films. This study examines two molecular sensitizers spanning the weak (a
      phosphonated Ruthenium complex) and strong (catechol) molecule-TiO(2) coupling
      regimes. It is shown that strong molecule-TiO(2) interactions give rise to
      photoinduced vibrational coherences at the interface between species. We suggest
      that the amplitudes of these coherences reflect the molecule-TiO(2) coupling
      strength and signify the delocalization of excited state wavefunctions.

PMID- 21895110
TI  - Range discrimination in ultrasonic vibrometry: theory and experiment.
AB  - A technique has been developed to demodulate periodic broadband ultrasonic
      interrogation signals that are returned from multiple scattering sites to
      simultaneously determine the low-frequency displacement time histories of each
      individual site. The technique employs a broadband periodic transmit signal. The
      motions of scattering sites are separately determined from the echoed receive
      signal by an algorithm involving comb filtering and pulse synthesis. This
      algorithm permits spatial resolution comparable to pulse-echo techniques and
      displacement sensitivities comparable to pure-tone techniques. A system based on
      this technique was used to image transient audio-frequency displacements on the
      order of 1-10 MUm peak (>= 50 nm/?Hz) that were produced by propagating shear
      waves in a tissue phantom. The system used concentric transmitting and receiving
      transducers and a carrier signal centered at 2.5 MHz with an 800 kHz bandwidth.
      The system was self-noise-limited and capable of detecting motions of strongly
      reflecting regions on the order of 1 nm/?Hz. System performance is limited by
      several factors including signal selection, component hardware, and ultrasonic
      propagation within the media of interest.

PMID- 21895148
TI  - Communication: highly accurate ozone formation potential and implications for
      kinetics.
AB  - Atmospheric ozone is formed by the O + O(2) exchange reaction followed by
      collisional stabilization of the O(3)(*) intermediate. The dynamics of the O +
      O(2) reaction and to a lesser extent the O(3) stabilization depend sensitively on
      the underlying potential energy surface, particularly in the asymptotic region.
      Highly accurate Davidson corrected multi-state multi-reference configuration
      interaction calculations reported here reveal that the minimal energy path for
      the formation of O(3) from O + O(2) is a monotonically decaying function of the
      atom-diatom distance and contains no "reef" feature found in previous ab initio
      calculations. The absence of a submerged barrier leads to an exchange rate
      constant with the correct temperature dependence and is in better agreement with
      experiment, as shown by quantum scattering calculations.

PMID- 21895149
TI  - Communication: a density functional with accurate fractional-charge and
      fractional-spin behaviour for s-electrons.
AB  - We develop a new density-functional approach combining physical insight from
      chemical structure with treatment of multi-reference character by real-space
      modeling of the exchange-correlation hole. We are able to recover, for the first
      time, correct fractional-charge and fractional-spin behaviour for atoms of groups
      1 and 2. Based on Becke's non-dynamical correlation functional [A. D. Becke, J.
      Chem. Phys. 119, 2972 (2003)] and explicitly accounting for core-valence
      separation and pairing effects, this method is able to accurately describe
      dissociation and strong correlation in s-shell many-electron systems.

PMID- 21895150
TI  - Communication: imaging wavefunctions in dissociative photoionization.
AB  - The dissociative ionization dynamics of excited electronic states of the xenon
      dimer, Xe(2), have been studied using velocity map ion imaging (VMI). A one
      colour, (2+1) resonant excitation scheme was employed to first excite and then
      ionize selected vibrational levels of the Xe(2) 6p (2)[(1)/(2)](0) 0(g)(+)
      Rydberg state. Cationic fragments were then detected by the VMI. The data provide
      an outstanding example of the reflection principle in photodissociation with the
      full nodal structure of the Rydberg state wavefunctions clearly observed in the
      final Xe(+) kinetic energy distributions without the need for scanning the
      excitation energy. Fitting of the observed distributions provides detailed and
      precise information on the form of the Xe(2)(+) I((1)/(2)g) potential energy
      curve involved which is in excellent agreement with the results of photoelectron
      imaging studies [Shubert and Pratt, J. Chem. Phys. 134, 044315 (2011)].
      Furthermore, the anisotropy of the product angular distributions yields
      information on the evolution of the electronic character of the ionic state with
      internuclear separation, R. The combination of the nature of dissociative
      ionization and the extent of the bound state wavefunctions provide information
      over an unusually wide range of internuclear separation R (DeltaR > 0.75 A). This
      would normally require scanning over a considerable energy region but is obtained
      in these studies at a fixed excitation energy.

PMID- 21895151
TI  - Communication: efficient counterpoise corrections by a perturbative approach.
AB  - We investigate the use of Hartree-Fock and density functional perturbative
      corrections for estimating the counterpoise correction (CPC) for interaction
      energies at the self-consistent field level. We test our approach using several
      popular basis sets on the S22 set of weakly bound systems, which can exhibit
      large basis set superposition errors. Our results show that the perturbative
      approaches typically recover over 95% of the CPC and can be up to twelve times
      faster to compute than the conventional methods and therefore provide an
      attractive alternative to calculating CPCs in the conventional way.

PMID- 21895152
TI  - Communication: extended multi-state complete active space second-order
      perturbation theory: energy and nuclear gradients.
AB  - The extended multireference quasi-degenerate perturbation theory, proposed by
      Granovsky [J. Chem. Phys. 134, 214113 (2011)], is combined with internally
      contracted multi-state complete active space second-order perturbation theory
      (XMS-CASPT2). The first-order wavefunction is expanded in terms of the union of
      internally contracted basis functions generated from all the reference functions,
      which guarantees invariance of the theory with respect to unitary rotations of
      the reference functions. The method yields improved potentials in the vicinity of
      avoided crossings and conical intersections. The theory for computing nuclear
      energy gradients for MS-CASPT2 and XMS-CASPT2 is also presented and the first
      implementation of these gradient methods is reported. A number of illustrative
      applications of the new methods are presented.

PMID- 21895153
TI  - Reciprocity in the degeneracies of some tetra-atomic molecular ions.
AB  - Various ab initio computations, as, e.g., in G. J. Halasz and A. Vibok, Int. J.
      Quantum Chem. 111, 342 (2011), have shown that in molecules of the type
      (HCCH)(+), when the extremal H atoms are distorted from a linear form but
      maintain a planar geometry, a pair of conical intersections (ci) occur at such
      positions that the ratios of the distortional coordinates of the two atoms are in
      the two ci's reciprocals of each other. These computations have here been
      extended to locate the ci's also for HCNH. The two groups of results are
      explained by simple analytic perturbational expressions for the energy
      differences of the lowest adjacent electronic states, with inclusion of excited
      state effects.

PMID- 21895154
TI  - An orbital-invariant and strictly size extensive post-Hartree-Fock correlation
      functional.
AB  - A strictly size extensive post-Hartree-Fock correlation functional being
      invariant with respect to orbital transformations within the occupied and virtual
      subspaces is presented. While avoiding the necessity to solve additional Z vector
      equations for the calculation of properties and energy gradients, this functional
      reproduces almost exactly the results of coupled-cluster singles doubles (CCSD)
      calculations. In particular, it is demonstrated that the method is rigorous in
      the sense that it can be systematically improved by the perturbative inclusion of
      triple excitations in the same way as CCSD. As to the computational cost, the
      presented approach is somewhat more expensive than the CCSD if the energy is
      variationally optimized with respect to both the orbitals and the excitation
      amplitudes. Replacement of orbital optimization by the Brueckner condition
      reduces the computational cost by a factor of two, thus making the method less
      expensive than CCSD.

PMID- 21895155
TI  - How accurate are the nonlinear chemical Fokker-Planck and chemical Langevin
      equations?
AB  - The chemical Fokker-Planck equation and the corresponding chemical Langevin
      equation are commonly used approximations of the chemical master equation. These
      equations are derived from an uncontrolled, second-order truncation of the
      Kramers-Moyal expansion of the chemical master equation and hence their accuracy
      remains to be clarified. We use the system-size expansion to show that chemical
      Fokker-Planck estimates of the mean concentrations and of the variance of the
      concentration fluctuations about the mean are accurate to order Omega(-3/2) for
      reaction systems which do not obey detailed balance and at least accurate to
      order Omega(-2) for systems obeying detailed balance, where Omega is the
      characteristic size of the system. Hence, the chemical Fokker-Planck equation
      turns out to be more accurate than the linear-noise approximation of the chemical
      master equation (the linear Fokker-Planck equation) which leads to mean
      concentration estimates accurate to order Omega(-1/2) and variance estimates
      accurate to order Omega(-3/2). This higher accuracy is particularly conspicuous
      for chemical systems realized in small volumes such as biochemical reactions
      inside cells. A formula is also obtained for the approximate size of the relative
      errors in the concentration and variance predictions of the chemical Fokker
      Planck equation, where the relative error is defined as the difference between
      the predictions of the chemical Fokker-Planck equation and the master equation
      divided by the prediction of the master equation. For dimerization and enzyme
      catalyzed reactions, the errors are typically less than few percent even when the
      steady-state is characterized by merely few tens of molecules.

PMID- 21895156
TI  - Breaking the carbon dimer: the challenges of multiple bond dissociation with full
      configuration interaction quantum Monte Carlo methods.
AB  - The full configuration interaction quantum Monte Carlo (FCIQMC) method, as well
      as its "initiator" extension (i-FCIQMC), is used to tackle the complex electronic
      structure of the carbon dimer across the entire dissociation reaction coordinate,
      as a prototypical example of a strongly correlated molecular system. Various
      basis sets of increasing size up to the large cc-pVQZ are used, spanning a fully
      accessible N-electron basis of over 10(12) Slater determinants, and the accuracy
      of the method is demonstrated in each basis set. Convergence to the FCI limit is
      achieved in the largest basis with only O[10(7)] walkers within random errorbars
      of a few tenths of a millihartree across the binding curve, and extensive
      comparisons to FCI, CCSD(T), MRCI, and CEEIS results are made where possible. A
      detailed exposition of the convergence properties of the FCIQMC methods is
      provided, considering convergence with elapsed imaginary time, number of walkers
      and size of the basis. Various symmetries which can be incorporated into the
      stochastic dynamic, beyond the standard abelian point group symmetry and spin
      polarisation are also described. These can have significant benefit to the
      computational effort of the calculations, as well as the ability to converge to
      various excited states. The results presented demonstrate a new benchmark
      accuracy in basis-set energies for systems of this size, significantly improving
      on previous state of the art estimates.

PMID- 21895157
TI  - An approximate density-functional method using the Harris-Foulkes functional.
AB  - We present a method which uses the results of a molecular Kohn-Sham calculation
      at a reference geometry to approximate the energy at many different geometries.
      The Kohn-Sham electron density of the reference geometry is decomposed into
      atomic fragments, which move with the nuclei to approximate the density at a new
      geometry and the energy is evaluated with the Harris-Foulkes functional.
      Preliminary results for a biological quantum-mechanics/molecular-mechanics
      trajectory are promising: the errors of reference-geometry Harris-Foulkes
      (compared to full self-consistent Kohn-Sham) for the PBE exchange-correlation
      functional have the same magnitude as the difference between the energies of PBE
      and BLYP.

PMID- 21895158
TI  - On the accuracy of the state space restriction approximation for spin dynamics
      simulations.
AB  - We present an algebraic foundation for the state space restriction approximation
      in spin dynamics simulations and derive applicability criteria as well as minimal
      basis set requirements for practically encountered simulation tasks. The results
      are illustrated with nuclear magnetic resonance (NMR), electron spin resonance
      (ESR), dynamic nuclear polarization (DNP), and spin chemistry simulations. It is
      demonstrated that state space restriction yields accurate results in systems
      where the time scale of spin relaxation processes approximately matches the time
      scale of the experiment. Rigorous error bounds and basis set requirements are
      derived.

PMID- 21895159
TI  - Incorporation of charge transfer into the explicit polarization fragment method
      by grand canonical density functional theory.
AB  - Molecular fragmentation algorithms provide a powerful approach to extending
      electronic structure methods to very large systems. Here we present a method for
      including charge transfer between molecular fragments in the explicit
      polarization (X-Pol) fragment method for calculating potential energy surfaces.
      In the conventional X-Pol method, the total charge of each fragment is preserved,
      and charge transfer between fragments is not allowed. The description of charge
      transfer is made possible by treating each fragment as an open system with
      respect to the number of electrons. To achieve this, we applied Mermin's finite
      temperature method to the X-Pol wave function. In the application of this method
      to X-Pol, the fragments are open systems that partially equilibrate their number
      of electrons through a quasithermodynamics electron reservoir. The number of
      electrons in a given fragment can take a fractional value, and the electrons of
      each fragment obey the Fermi-Dirac distribution. The equilibrium state for the
      electrons is determined by electronegativity equalization with conservation of
      the total number of electrons. The amount of charge transfer is controlled by re
      interpreting the temperature parameter in the Fermi-Dirac distribution function
      as a coupling strength parameter. We determined this coupling parameter so as to
      reproduce the charge transfer energy obtained by block localized energy
      decomposition analysis. We apply the new method to ten systems, and we show that
      it can yield reasonable approximations to potential energy profiles, to charge
      transfer stabilization energies, and to the direction and amount of charge
      transferred.

PMID- 21895160
TI  - The theoretical current-voltage dependence of a non-degenerate disordered organic
      material obtained with conductive atomic force microscopy.
AB  - We develop a simple continuum model for the current voltage characteristics of a
      material as measured by the conducting atomic force microscopy, including space
      charge effects. We address the effect of the point contact on the magnitude of
      the current and on the transition voltages between the different current regimes
      by comparing these with the corresponding expressions obtained with planar
      electrodes.

PMID- 21895161
TI  - Using the charge-stabilization technique in the double ionization potential
      equation-of-motion calculations with dianion references.
AB  - The charge-stabilization method is applied to double ionization potential
      equation-of-motion (EOM-DIP) calculations to stabilize unstable dianion reference
      functions. The auto-ionizing character of the dianionic reference states spoils
      the numeric performance of EOM-DIP limiting applications of this method. We
      demonstrate that reliable excitation energies can be computed by EOM-DIP using a
      stabilized resonance wave function instead of the lowest energy solution
      corresponding to the neutral + free electron(s) state of the system. The details
      of charge-stabilization procedure are discussed and illustrated by examples. The
      choice of optimal stabilizing Coulomb potential, which is strong enough to
      stabilize the dianion reference, yet, minimally perturbs the target states of the
      neutral, is the crux of the approach. Two algorithms of choosing optimal
      parameters of the stabilization potential are presented. One is based on the
      orbital energies, and another--on the basis set dependence of the total Hartree
      Fock energy of the reference. Our benchmark calculations of the singlet-triplet
      energy gaps in several diradicals show a remarkable improvement of the EOM-DIP
      accuracy in problematic cases. Overall, the excitation energies in diradicals
      computed using the stabilized EOM-DIP are within 0.2 eV from the reference EOM
      spin-flip values.

PMID- 21895162
TI  - Least constraint approach to the extraction of internal motions from molecular
      dynamics trajectories of flexible macromolecules.
AB  - We propose a rigorous method for removing rigid-body motions from a given
      molecular dynamics trajectory of a flexible macromolecule. The method becomes
      exact in the limit of an infinitesimally small sampling step for the input
      trajectory. In a recent paper [G. Kneller, J. Chem. Phys. 128, 194101 (2008)],
      one of us showed that virtual internal atomic displacements for small time
      increments can be derived from Gauss' principle of least constraint, which leads
      to a rotational superposition problem for the atomic coordinates in two
      consecutive time frames of the input trajectory. Here, we demonstrate that the
      accumulation of these displacements in a molecular-fixed frame, which evolves in
      time according to the virtual rigid-body motions, leads to the desired trajectory
      for internal motions. The atomic coordinates in the input and output trajectory
      are related by a roto-translation, which guarantees that the internal energy of
      the molecule is left invariant. We present a convenient implementation of our
      method, in which the accumulation of the internal displacements is performed
      implicitly. Two numerical examples illustrate the difference to the classical
      approach for removing macromolecular rigid-body motions, which consists of
      aligning its configurations in the input trajectory with a fixed reference
      structure.

PMID- 21895163
TI  - Extension of the invariant environment refinement technique + reverse Monte Carlo
      method of structural modelling for interpreting experimental structure factors:
      the cases of amorphous silicon, phosphorus, and liquid argon.
AB  - The invariant environment refinement technique, as applied to reverse Monte Carlo
      modelling [invariant environment refinement technique + reverse Monte Carlo
      (INVERT + RMC); M. J. Cliffe, M. T. Dove, D. A. Drabold, and A. L. Goodwin, Phys.
      Rev. Lett. 104, 125501 (2010)], is extended so that it is now applicable for
      interpreting the structure factor (instead of the pair distribution function).
      The new algorithm, called the local invariance calculation, is presented by the
      examples of amorphous silicon, phosphorus, and liquid argon. As a measure of the
      effectiveness of the new algorithm, the ratio of exactly fourfold coordinated Si
      atoms was larger than obtained previously by the INVERT-RMC scheme.

PMID- 21895164
TI  - Calculation of multiple initial state selected reaction probabilities from
      Chebyshev flux-flux correlation functions: influence of reactant internal
      excitations on H + H2O -> OH + H2.
AB  - A Chebyshev-based flux-flux correlation function approach is introduced for
      calculating multiple initial state selected reaction probabilities for
      bimolecular reactions. Based on the quantum transition-state theory, this
      approach propagates, with the exact Chebyshev propagator, transition-state wave
      packets towards the reactant asymptote. It is accurate and efficient if many
      initial state selected reaction probabilities are needed. This approach is
      applied to the title reaction to elucidate the influence of the H(2)O ro
      vibrational states on its reactivity. Results from several potential energy
      surfaces are compared.

PMID- 21895165
TI  - Pair correlation function integrals: computation and use.
AB  - We describe a method for extending radial distribution functions obtained from
      molecular simulations of pure and mixed molecular fluids to arbitrary distances.
      The method allows total correlation function integrals to be reliably calculated
      from simulations of relatively small systems. The long-distance behavior of
      radial distribution functions is determined by requiring that the corresponding
      direct correlation functions follow certain approximations at long distances. We
      have briefly described the method and tested its performance in previous
      communications [R. Wedberg, J. P. O'Connell, G. H. Peters, and J. Abildskov, Mol.
      Simul. 36, 1243 (2010); Fluid Phase Equilib. 302, 32 (2011)], but describe here
      its theoretical basis more thoroughly and derive long-distance approximations for
      the direct correlation functions. We describe the numerical implementation of the
      method in detail, and report numerical tests complementing previous results. Pure
      molecular fluids are here studied in the isothermal-isobaric ensemble with
      isothermal compressibilities evaluated from the total correlation function
      integrals and compared with values derived from volume fluctuations. For systems
      where the radial distribution function has structure beyond the sampling limit
      imposed by the system size, the integration is more reliable, and usually more
      accurate, than simple integral truncation.

PMID- 21895166
TI  - Analytic energy gradients for the spin-free exact two-component theory using an
      exact block diagonalization for the one-electron Dirac Hamiltonian.
AB  - We report the implementation of analytic energy gradients for the evaluation of
      first-order electrical properties and nuclear forces within the framework of the
      spin-free (SF) exact two-component (X2c) theory. In the scheme presented here,
      referred to in the following as SFX2c-1e, the decoupling of electronic and
      positronic solutions is performed for the one-electron Dirac Hamiltonian in its
      matrix representation using a single unitary transformation. The resulting two
      component one-electron matrix Hamiltonian is combined with untransformed two
      electron interactions for subsequent self-consistent-field and electron
      correlated calculations. The "picture-change" effect in the calculation of
      properties is taken into account by considering the full derivative of the two
      component Hamiltonian matrix with respect to the external perturbation. The
      applicability of the analytic-gradient scheme presented here is demonstrated in
      benchmark calculations. SFX2c-1e results for the dipole moments and electric
      field gradients of the hydrogen halides are compared with those obtained from
      nonrelativistic, SF high-order Douglas-Kroll-Hess, and SF Dirac-Coulomb
      calculations. It is shown that the use of untransformed two-electron interactions
      introduces rather small errors for these properties. As a first application of
      the analytic geometrical gradient, we report the equilibrium geometry of
      methylcopper (CuCH(3)) determined at various levels of theory.

PMID- 21895167
TI  - Velocity-scaling optimized replica exchange molecular dynamics of proteins in a
      hybrid explicit/implicit solvent.
AB  - We propose a scheme for replica exchange molecular dynamics of proteins in
      explicit solvent that minimizes the number of required replicas using velocity
      rescaling. Our approach relies on a hybrid method where the protein evolves at
      each temperature in an explicit solvent, but replica exchange moves utilize an
      implicit solvent term. The two terms are coupled through the velocity rescaling.
      We test the efficiency of this approach for a common test case, the trp-cage
      protein.

PMID- 21895168
TI  - Comparison of Brownian dynamics algorithms with hydrodynamic interaction.
AB  - The hydrodynamic interaction is an essential effect to consider in Brownian
      dynamics simulations of polymer and nanoparticle dilute solutions. Several
      mathematical approaches can be used to build Brownian dynamics algorithms with
      hydrodynamic interaction, the most common of them being the exact but time
      demanding Cholesky decomposition and the Chebyshev polynomial expansion.
      Recently, Geyer and Winter [J. Chem. Phys. 130, 1149051 (2009)] have proposed a
      new approximation to treat the hydrodynamic interaction that seems quite
      efficient and is increasingly used. So far, a systematic comparison among those
      approaches has not been clearly made. In this paper, several features and the
      efficiency of typical implementations of those approaches are evaluated by using
      bead-and-spring chain models. The different sensitivity to the bead overlap
      detected for the different implementations may be of interest to select the
      suitable algorithm for a given simulation.

PMID- 21895169
TI  - A systematic formulation of the virial expansion for nonadditive interaction
      potentials.
AB  - A new formulation of the virial expansion for a classical gas is derived without
      the restriction to pairwise-additive interaction potentials. Explicit expressions
      up to the eighth virial coefficient, suitable for numerical evaluation, are given
      in the form of integrals over sums of cluster diagrams. Compared with previous
      approaches, the number of cluster diagrams increases more moderately with
      increasing order of the virial coefficient. Thus, the new formulation should be
      particularly useful for the computation of high-order virial coefficients.

PMID- 21895170
TI  - Application of an efficient multireference approach to free-base porphin and
      metalloporphyrins: ground, excited, and positive ion states.
AB  - The improved virtual orbital-complete active space configuration interaction (IVO
      CASCI) method is applied to determine the geometries of the ground state of free
      base porphin and its metal derivatives, magnesium and zinc porphyrins. The
      vertical excitation energies and ionization potentials are computed at these
      optimized geometries using an IVO-based version of multireference Moller-Plesset
      (IVO-MRMP) perturbation theory. The geometries and excitation energies obtained
      from the IVO-CASCI and IVO-MRMP methods agree well with experiment and with other
      correlated many-body methods. We also provide the ground state vibrational
      frequencies for free-base porphin and Mg-porphyrin. All frequencies are real in
      contrast to self-consistent field treatments which yield an imaginary frequency.
      Ground state normal mode frequencies (scaled) of free-base porphin and magnesium
      porphyrin from IVO-CASCI and complete active space self-consistent field methods
      are quite similar and are consistent with Becke-Slater-Hartree-Fock exchange and
      Lee-Yang-Parr correlation density functional theory calculations and with
      experiment. In addition, geometries are determined for low-lying excited state
      triplets and for positive ion states of the molecules. To our knowledge, no prior
      experimental and theoretical data are available for these excited state
      geometries of magnesium and zinc porphyrins. Given that the IVO-CASCI and IVO
      MRMP computed geometries and excitation energies agree favorably with experiment
      and with available theoretical data, our predicted excited state geometries
      should be equally accurate.

PMID- 21895171
TI  - Closed-shell ring coupled cluster doubles theory with range separation applied on
      weak intermolecular interactions.
AB  - We explore different variants of the random phase approximation to the
      correlation energy derived from closed-shell ring-diagram approximations to
      coupled cluster doubles theory. We implement these variants in range-separated
      density-functional theory, i.e., by combining the long-range random phase
      approximations with short-range density-functional approximations. We perform
      tests on the rare-gas dimers He(2), Ne(2), and Ar(2), and on the weakly
      interacting molecular complexes of the S22 set of Jurecka et al. [P. Jurecka, J.
      Sponer, J. Cerny, and P. Hobza, Phys. Chem. Chem. Phys. 8, 1985 (2006)]. The two
      best variants correspond to the ones originally proposed by Szabo and Ostlund [A.
      Szabo and N. S. Ostlund, J. Chem. Phys. 67, 4351 (1977)]. With range separation,
      they reach mean absolute errors on the equilibrium interaction energies of the
      S22 set of about 0.4 kcal/mol, corresponding to mean absolute percentage errors
      of about 4%, with the aug-cc-pVDZ basis set.

PMID- 21895172
TI  - Self-consistency in frozen-density embedding theory based calculations.
AB  - The bi-functional for the non-electrostatic part of the exact embedding potential
      of frozen-density embedding theory (FDET) depends on whether the embedded part is
      described by means of a real interacting many-electron system or the reference
      system of non-interacting electrons (see [Wesolowski, Phys. Rev. A. 77, 11444
      (2008)]). The difference deltaDeltaF(MD)[rho(A)]/deltarho(A)(r<combining arrow>),
      where DeltaF(MD)[rho(A)] is the functional bound from below by the correlation
      functional E(c)[rho(A)] and from above by zero. Taking into account
      DeltaF(MD)[rho(A)] in both the embedding potential and in energy is indispensable
      for assuring that all calculated quantities are self-consistent and that FDET
      leads to the exact energy and density in the limit of exact functionals. Since
      not much is known about good approximations for DeltaF(MD)[rho(A)], we examine
      numerically the adequacy of neglecting DeltaF(MD)[rho(A)] entirely. To this end,
      we analyze the significance of deltaDeltaF(MD)[rho(A)]/deltarho(A)(r<combining
      arrow>) in the case where the magnitude of DeltaF(MD)[rho(A)] is the largest,
      i.e., for Hartree-Fock wavefunction. In hydrogen bonded model systems, neglecting
      deltaDeltaF(MD)[rho(A)]/deltarho(A)(r<combining arrow>) in the embedding
      potential marginally affects the total energy (less than 5% change in the
      interaction energy) but results in qualitative changes in the calculated hydrogen
      bonding induced shifts of the orbital energies. Based on this estimation, we
      conclude that neglecting deltaDeltaF(MD)[rho(A)]/deltarho(A)(r<combining arrow>)
      may represent a good approximation for multi-reference variational methods using
      adequate choice for the active space. Doing the same for single-reference
      perturbative methods is not recommended. Not only it leads to violation of self
      consistency but might result in large effect on orbital energies. It is shown
      also that the errors in total energy due to neglecting
      deltaDeltaF(MD)[rho(A)]/deltarho(A)(r<combining arrow>) do not cancel but rather
      add up to the errors due to approximation for the bi-functional of the non
      additive kinetic potential.

PMID- 21895173
TI  - Near-field: a finite-difference time-dependent method for simulation of
      electrodynamics on small scales.
AB  - We develop near-field (NF), a very efficient finite-difference time-dependent
      (FDTD) approach for simulating electromagnetic systems in the near-field regime.
      NF is essentially a time-dependent version of the quasistatic frequency-dependent
      Poisson algorithm. We assume that the electric field is longitudinal, and hence
      propagates only a set of time-dependent polarizations and currents. For near
      field scales, the time step (dt) is much larger than in the usual Maxwell FDTD
      approach, as it is not related to the velocity of light; rather, it is determined
      by the rate of damping and plasma oscillations in the material, so dt = 2.5 a.u.
      was well converged in our simulations. The propagation in time is done via a
      leapfrog algorithm much like Yee's method, and only a single spatial convolution
      is needed per time step. In conjunction, we also develop a new and very accurate
      8 and 9 Drude-oscillators fit to the permittivity of gold and silver, desired
      here because we use a large time step. We show that NF agrees with Mie-theory in
      the limit of small spheres and that it also accurately describes the evolution of
      the spectral shape as a function of the separation between two gold or silver
      spheres. The NF algorithm is especially efficient for systems with small scale
      dynamics and makes it very simple to introduce additional effects such as
      embedding.

PMID- 21895174
TI  - A density functional theory based estimation of the anharmonic contributions to
      the free energy of a polypeptide helix.
AB  - We have employed density functional theory to determine the temperature
      dependence of the intrinsic stability of an infinite poly-L-alanine helix. The
      most relevant helix types, i.e., the alpha- and the 3(10)-helix, and several
      unfolded conformations, which serve as reference for the stability analysis, have
      been included. For the calculation of the free energies for the various chain
      conformations we have explicitly included both, harmonic and anharmonic
      contributions. The latter have been calculated by means of a thermodynamic
      integration approach employing stochastic Langevin molecular dynamics, which is
      shown to provide a dramatic increase in the computational efficiency as compared
      to commonly employed deterministic molecular dynamics schemes. Employing this
      approach we demonstrate that the anharmonic part of the free energy amounts to
      the order of 0.1-0.4 kcal/mol per peptide unit for all analysed conformations.
      Although small, the anharmonic contribution stabilizes the helical conformations
      with respect to the fully extended structure.

PMID- 21895175
TI  - Master equation for a chemical wave front with perturbation of local equilibrium.
AB  - In order to develop a stochastic description of gaseous reaction-diffusion
      systems, which includes a reaction-induced departure from local equilibrium, we
      derive a modified expression of the master equation from analytical calculations
      based on the Boltzmann equation. We apply the method to a chemical wave front of
      Fisher-Kolmogorov-Petrovsky-Piskunov type, whose propagation speed is known to be
      sensitive to small perturbations. The results of the modified master equation are
      compared successfully with microscopic simulations of the particle dynamics using
      the direct simulation Monte Carlo method. The modified master equation
      constitutes an efficient tool at the mesoscopic scale, which incorporates the
      nonequilibrium effect without need of determining the particle velocity
      distribution function.

PMID- 21895176
TI  - The chemical dynamics of nanosensors capable of single-molecule detection.
AB  - Recent advances in nanotechnology have produced the first sensor transducers
      capable of resolving the adsorption and desorption of single molecules. Examples
      include near infrared fluorescent single-walled carbon nanotubes that report
      single-molecule binding via stochastic quenching. A central question for the
      theory of such sensors is how to analyze stochastic adsorption events and extract
      the local concentration or flux of the analyte near the sensor. In this work, we
      compare algorithms of varying complexity for accomplishing this by first
      constructing a kinetic Monte Carlo model of molecular binding and unbinding to
      the sensor substrate and simulating the dynamics over wide ranges of forward and
      reverse rate constants. Methods involving single-site probability calculations,
      first and second moment analysis, and birth-and-death population modeling are
      compared for their accuracy in reconstructing model parameters in the presence
      and absence of noise over a large dynamic range. Overall, birth-and-death
      population modeling was the most robust in recovering the forward rate constants,
      with the first and second order moment analysis very efficient when the forward
      rate is large (>10(-3) s(-1)). The precision decreases with increasing noise,
      which we show masks the existence of underlying states. Precision is also
      diminished with very large forward rate constants, since the sensor surface
      quickly and persistently saturates.

PMID- 21895177
TI  - Adaptive stochastic methods for sampling driven molecular systems.
AB  - Thermostatting methods are discussed in the context of canonical sampling in the
      presence of driving stochastic forces. Generalisations of the Nose-Hoover method
      and Langevin dynamics are introduced which are able to dissipate excess heat
      introduced by steady Brownian perturbation (without a priori knowledge of its
      strength) while preserving ergodicity. Implementation and parameter selection are
      considered. It is demonstrated using numerical experiments that the methods
      derived can adaptively control the target canonical ensemble in the presence of
      nonlinear driving perturbations.

PMID- 21895178
TI  - Liquid-vapor interfacial properties of vibrating square well chains.
AB  - Liquid-vapor interfacial properties of square well chains are calculated. Surface
      tension, orthobaric densities, and vapor pressures are reported. Spinodal
      decomposition with a discontinuous molecular dynamics simulation program is used
      to obtain the results which are compared to previously published data for
      orthobaric densities and vapor pressures. In order to analyze the effect of the
      chain stiffness results for near tangent and overlapping linear chains as well as
      angled chains are obtained. Properties are calculated for linear chains of 2, 4,
      and 8 spheres for intramolecular distances of 0.97, 0.6, and 0.4 as well as for
      angled chains of 4 and 8 spheres and intramolecular distances of 0.4. The
      complete series of fully flexible near tangent square well chains is also studied
      (chains of 2, 4, 8, 12, and 16 particles with intramolecular distances of 0.97).
      The corresponding states principle applies to most of the systems considered.
      Critical properties values are reported as obtained from orthobaric densities,
      surface tensions, and vapor pressures. For the near tangent chains the critical
      temperatures increase with chain length but the rate of increment tends to zero
      for the longest chains considered. When the stiffness of the chain increases
      (intramolecular distance from 1 , 0.6, and 0.4) this saturation effect is either
      not present or reverses itself. The surface tension increases with the length of
      the chain while the width of the interface decreases.

PMID- 21895179
TI  - Excited state electron transfer precedes proton transfer following irradiation of
      the hydrogen-bonded single water complex of 7-azaindole with UV light.
AB  - High resolution electronic spectra of the single water complex of 7-azaindole
      (7AIW) and of a deuterated analog (7AIW-d(3)) have been recorded in a molecular
      beam, both in the absence and presence of an applied electric field. The obtained
      data include the rotational constants of both complexes in their ground (S(0))
      and first excited (S(1)) electronic states, their S(1)-S(0) electronic transition
      moment and axis-tilting angles, and their permanent electric dipole moments
      (EDM's) in both electronic states. Analyses of these data show that the water
      molecule forms two hydrogen bonds with 7AI, a donor O-H...N(7) bond and an
      acceptor O...H-N(1) bond. The resulting structure has a small EDM in the S(0)
      state (MU = 0.54 D) but a greatly enhanced EDM in the S(1) state (MU = 3.97 D).
      We deduce from the EDM's of the component parts that 0.281 e(-) of charge is
      transferred from the acidic N(1)-H site to the basic N(7) site upon UV excitation
      of 7AIW, but that water-assisted proton transfer from N(1) to N(7) does not
      occur. A model of the resulting electrostatic interactions in the solute-solvent
      pair predicts a solvent-induced red-shift of 1260 cm(-1) which compares favorably
      to the experimental value of 1290 cm(-1).

PMID- 21895180
TI  - Inner-shell single and double ionization potentials of aminophenol isomers.
AB  - A comprehensive study of single and double core ionization potentials of the
      aminophenol molecule is reported. The role of relaxation, correlation,
      relativistic, and basis set effects in these potentials is clarified. Special
      attention is paid to the isomer dependence of the single and double core
      ionization potentials. Some of them are also compared with the respective values
      of the phenol and aniline molecules. It is shown that the core level single
      ionization potentials of the para-, meta-, and ortho-aminophenol molecules differ
      only slightly from each other, rendering these structural isomers challenging to
      distinguish for conventional x-ray photoelectron spectroscopy. In contrast, the
      energy needed to remove two core electrons from different atoms depends
      noticeably on the mutual arrangement and even on the relative orientations of the
      hydroxyl and amine groups. Together with the electrostatic repulsion between the
      two core holes, relaxation effects accompanying double core ionization play a
      crucial role here. The pronounced sensitivity of the double ionization
      potentials, therefore, enables a spectroscopic characterization of the electronic
      structure of aminophenol isomers by means of x-ray two-photon photoelectron
      spectroscopy.

PMID- 21895181
TI  - The rotational spectra, potential function, Born-Oppenheimer breakdown, and
      hyperfine structure of GeSe and GeTe.
AB  - The pure rotational spectra of 18 and 21 isotopic species of GeSe and GeTe have
      been measured in the frequency range 5-24 GHz using a Fabry-Perot-type resonator
      pulsed-jet Fourier-transform microwave spectrometer. Gaseous samples of both
      chalcogenides were prepared by a combined dc discharge/laser ablation technique
      and stabilized in supersonic jets of Ne. Global multi-isotopologue analyses of
      the derived rotational data, together with literature high-resolution infrared
      data, produced very precise Dunham parameters, as well as rotational constant
      Born-Oppenheimer breakdown (BOB) coefficients (delta(01)) for Ge, Se, and Te. A
      direct fit of the same datasets to an appropriate radial Hamiltonian yielded
      analytic potential-energy functions and BOB radial functions for the X(1)Sigma(+)
      electronic state of both GeSe and GeTe. Additionally, the electric quadrupole and
      magnetic hyperfine interactions produced by the nuclei (73)Ge, (77)Se, and
      (125)Te were observed, yielding much improved quadrupole coupling constants and
      first determinations of the spin-rotation parameters.

PMID- 21895182
TI  - Unimolecular dissociation of anthracene and acridine cations: the importance of
      isomerization barriers for the C2H2 loss and HCN loss channels.
AB  - The loss of C(2)H(2) is a low activation energy dissociation channel for
      anthracene (C(14)H(10)) and acridine (C(13)H(9)N) cations. For the latter ion
      another prominent fragmentation pathway is the loss of HCN. We have studied these
      two dissociation channels by collision induced dissociation experiments of 50 keV
      anthracene cations and protonated acridine, both produced by electrospray
      ionization, in collisions with a neutral xenon target. In addition, we have
      carried out density functional theory calculations on possible reaction pathways
      for the loss of C(2)H(2) and HCN. The mass spectra display features of multi-step
      processes, and for protonated acridine the dominant first step process is the
      loss of a hydrogen from the N site, which then leads to C(2)H(2)/HCN loss from
      the acridine cation. With our calculations we have identified three pathways for
      the loss of C(2)H(2) from the anthracene cation, with three different cationic
      products: 2-ethynylnaphthalene, biphenylene, and acenaphthylene. The third
      product is the one with the overall lowest dissociation energy barrier. For the
      acridine cation our calculated pathway for the loss of C(2)H(2) leads to the 3
      ethynylquinoline cation, and the loss of HCN leads to the biphenylene cation.
      Isomerization plays an important role in the formation of the non-ethynyl
      containing products. All calculated fragmentation pathways should be accessible
      in the present experiment due to substantial energy deposition in the collisions.

PMID- 21895183
TI  - The k-j-j' vector correlation in inelastic and reactive scattering.
AB  - Quasi-classical trajectory (QCT) methods are presented which allow
      characterization of the angular momentum depolarization of the products of
      inelastic and reactive scattering. The particular emphasis of the theory is on
      three-vector correlations, and on the connection with the two-vector correlation
      between the initial and final angular momenta, j and j', which is amenable to
      experimental measurement. The formal classical theory is presented, and
      computational results for NO(A) + He are used to illustrate the type of
      mechanistic information provided by analysis of the two- and three-vector
      correlations. The classical j-j' two-vector correlation results are compared with
      quantum mechanical calculations, and are shown to be in good agreement. The data
      for NO(A) + He support previous conclusions [M. Brouard, H. Chadwick, Y.-P.
      Chang, R. Cireasa, C. J. Eyles, A. O. L. Via, N. Screen, F. J. Aoiz, and J. Klos,
      J. Chem. Phys. 131, 104307 (2009)] that this system is only weakly depolarizing.
      Furthermore, it is shown that the projection of j along the kinematic apse is
      nearly conserved for this system under thermal collision energy conditions.

PMID- 21895184
TI  - Collisional angular momentum depolarization of OH(A) and NO(A) by Ar: a
      comparison of mechanisms.
AB  - This paper discusses the contrasting mechanisms of collisional angular momentum
      depolarization of OH(A(2)Sigma(+)) and NO(A(2)Sigma(+)) by Ar. New experimental
      results are presented for the collisional depolarization of OH(A) + Ar under both
      thermal and superthermal collision conditions, including cross sections for loss
      of both angular momentum orientation and alignment. Previous work on the two
      systems is summarized. It is shown that NO(A) + Ar depolarization is dominated by
      impulsive events in which the projection of the angular momentum, j, along the
      kinematic apse, a, is nearly conserved, and in which the majority of the
      trajectories can be described as "nearside." By contrast, at the relatively low
      collision energies sampled at 300 K, OH(A) + Ar depolarization is dominated by
      attractive collisions, which show a preponderance of "farside" trajectories.
      There is also evidence for very long-lived, complex type trajectories in which
      OH(A) and Ar orbit each other for several rotational periods prior to separation.
      Nevertheless, there is still a clear preference for conservation of the
      projection of j along the kinematic apse for both elastic and inelastic
      collisions. Experimental and theoretical results reveal that, as the collision
      energy is raised, the depolarization of OH(A) by Ar becomes more impulsive-like
      in nature.

PMID- 21895185
TI  - Deflection of rotating symmetric top molecules by inhomogeneous fields.
AB  - We consider deflection of rotating symmetric top molecules by inhomogeneous
      optical and static electric fields, compare results with the case of linear
      molecules, and find new singularities in the distribution of the scattering
      angle. Scattering of the prolate/oblate molecules is analyzed in detail, and it
      is shown that the process can be efficiently controlled by means of short and
      strong femtosecond laser pulses. In particular, the angular dispersion of the
      deflected molecules may be dramatically reduced by laser-induced molecular
      prealignment. We first study the problem by using a simple classical model, and
      then find similar results by means of more sophisticated methods, including the
      formalism of adiabatic invariants and direct numerical simulation of the Euler
      Lagrange equations of motion. The suggested control scheme opens new ways for
      many applications involving molecular focusing, guiding, and trapping by optical
      and static fields.

PMID- 21895186
TI  - Ab initio virial equation of state for argon using a new nonadditive three-body
      potential.
AB  - An ab initio nonadditive three-body potential for argon has been developed using
      quantum-chemical calculations at the CCSD(T) and CCSDT levels of theory. Applying
      this potential together with a recent ab initio pair potential from the
      literature, the third and fourth to seventh pressure virial coefficients of argon
      were computed by standard numerical integration and the Mayer-sampling Monte
      Carlo method, respectively, for a wide temperature range. All calculated virial
      coefficients were fitted separately as polynomials in temperature. The results
      for the third virial coefficient agree with values evaluated directly from
      experimental data and with those computed for other nonadditive three-body
      potentials. We also redetermined the second and third virial coefficients from
      the best experimental prhoT data utilizing the computed higher virial
      coefficients as constraints. Thus, a significantly closer agreement of the
      calculated third virial coefficients with the experimental data was achieved. For
      different orders of the virial expansion, prhoT data have been calculated and
      compared with results from high quality measurements in the gaseous and
      supercritical region. The theoretically predicted pressures are within the very
      small experimental errors of +/-0.02% for p <= 12 MPa in the supercritical region
      near room temperature, whereas for subcritical temperatures the deviations
      increase up to +0.3%. The computed pressure at the critical density and
      temperature is about 1.3% below the experimental value. At pressures between 200
      MPa and 1000 MPa and at 373 K, the calculated values deviate by 1% to 9% from the
      experimental results.

PMID- 21895187
TI  - Ab initio investigation on ion-associated species and association process in
      aqueous Na2SO4 and Na2SO4/MgSO4 solutions.
AB  - In the present paper, the possible ion associated species in pure Na(2)SO(4) and
      mixed Na(2)SO(4)/MgSO(4) aqueous solutions are investigated via the ab initio
      method at the HF/6-31+G* level. The vibrational v(1)-SO(4)(2-) band is analyzed.
      For the unhydrated species, when the number of metal ions around the SO(4)(2-)
      ion is less than 3, the dominating effect to the v(1)-SO(4)(2-) band is the
      polarization of the cations, while the M-O bonding will be dominating as the
      number is equal to or more than 3. For the hydrated species, the coordinated
      structures of the Na(+) ion in all ion pairs are not stable due to the strong
      effect of the SO(4)(2-) ion but relatively stable in the triple ion (TI) clusters
      since there are fewer vacant hydration sites around the SO(4)(2-). The v(1)
      SO(4)(2-) frequencies are close to that of the hydrated SO(4)(2-) ion in the ion
      pairs and larger in both Na(2)SO(4) and Na(2)SO(4)/MgSO(4) TI clusters. On the
      basis of our calculated results, the evolvement of Raman spectra in the
      Na(2)SO(4)/MgSO(4) droplet with the molar ratio of 1:1 is explained.

PMID- 21895188
TI  - Weak intermolecular interactions in gas-phase nuclear magnetic resonance.
AB  - Gas-phase nuclear magnetic resonance (NMR) spectra demonstrating the effect of
      weak intermolecular forces on the NMR shielding constants of the interacting
      species are reported. We analyse the interaction of the molecular hydrogen
      isotopomers with He, Ne, and Ar, and the interaction in the He-CO(2) dimer. The
      same effects are studied for all these systems in the ab initio calculations. The
      comparison of the experimental and computed shielding constants is shown to
      depend strongly on the treatment of the bulk susceptibility effects, which
      determine in practice the pressure dependence of the experimental values. Best
      agreement of the results is obtained when the bulk susceptibility correction in
      rare gas solvents is evaluated from the analysis of the He-rare gas interactions,
      and when the shielding of deuterium in D(2)-rare gas systems is considered.

PMID- 21895189
TI  - Electronic and vibrational spectroscopy of intermediates in methane-to-methanol
      conversion by CoO+.
AB  - At room temperature, cobalt oxide cations directly convert methane to methanol
      with high selectivity but very low efficiency. Two potential intermediates of
      this reaction, the [HO-Co-CH(3)](+) insertion intermediate and [H(2)O
      Co=CH(2)](+) aquo-carbene complex are produced in a laser ablation source and
      characterized by electronic and vibrational spectroscopy. Reaction of laser
      ablated cobalt cations with different organic precursors seeded in a carrier gas
      produces the intermediates, which subsequently expand into vacuum and cool. Ions
      are extracted into a time-of-flight mass spectrometer and spectra are measured
      via photofragment spectroscopy. Photodissociation of [HO-Co-CH(3)](+) in the
      visible and via infrared multiple photon dissociation (IRMPD) makes only Co(+) +
      CH(3)OH, while photodissociation of [H(2)O-Co=CH(2)](+) produces CoCH(2)(+) +
      H(2)O. The electronic spectrum of [HO-Co-CH(3)](+) shows progressions in the
      excited state Co-C stretch (335 cm(-1)) and O-Co-C bend (90 cm(-1)); the IRMPD
      spectrum gives nu(OH) = 3630 cm(-1). The [HO-Co-CH(3)](+)(Ar) complex has been
      synthesized and its vibrational spectrum measured in the O-H stretching region.
      The resulting spectrum is sharper than that obtained via IRMPD and gives nu(OH) =
      3642 cm(-1). Also, an improved potential energy surface for the reaction of
      CoO(+) with methane has been developed using single point energies calculated by
      the CBS-QB3 method for reactants, intermediates, transition states and products.

PMID- 21895190
TI  - Dissociation energy and vibrational predissociation dynamics of the ammonia
      dimer.
AB  - Experiments using infrared excitation of either the intramolecular symmetric N-H
      stretch (nu(NH,S)) or the intramolecular antisymmetric N-H stretch (nu(NH,A)) of
      the ammonia dimer ((NH(3))(2)) in combination with velocity-map ion imaging
      provide new information on the dissociation energy of the dimer and on the energy
      disposal in its dissociation. Ion imaging using resonance enhanced multiphoton
      ionization to probe individual rovibrational states of one of the ammonia monomer
      fragments provides recoil speed distributions. Analyzing these distributions for
      different product states gives a dissociation energy of D(0) = 660 +/- 20 cm(-1)
      for the dimer. Fitting the distributions shows that rotations are excited up to
      their energetic limit and determines the correlation of the fragment vibrations.
      The fragments NH(3)(nu(2) = 3(+)) and NH(3)(nu(2) = 2(+)) have a vibrational
      ground-state partner NH(3)(nu = 0), but NH(3)(nu(2) = 1(+)) appears in
      partnership with another fragment in nu(2) = 1. This propensity is consistent
      with the idea of minimizing the momentum gap between the initial and final states
      by depositing a substantial fraction of the available energy into internal
      excitation.

PMID- 21895191
TI  - Optical method for measuring thermal accommodation coefficients using a
      whispering-gallery microresonator.
AB  - A novel optical method has been developed for the measurement of thermal
      accommodation coefficients in the temperature-jump regime. The temperature
      dependence of the resonant frequency of a fused-silica microresonator's
      whispering-gallery mode is used to measure the rate at which the microresonator
      comes into thermal equilibrium with the ambient gas. The thermal relaxation time
      is related to the thermal conductivity of the gas under some simplifying
      assumptions and measuring this time as a function of gas pressure determines the
      thermal accommodation coefficient. Using a low-power tunable diode laser of
      wavelength around 1570 nm to probe a microsphere's whispering-gallery mode
      through tapered-fiber coupling, we have measured the accommodation coefficients
      of air, helium, and nitrogen on fused silica at room temperature. In addition, by
      applying thin-film coatings to the microsphere's surface, we have demonstrated
      that accommodation coefficients can be measured for various gases on a wide range
      of modified surfaces using this method.

PMID- 21895192
TI  - Carbonyl vibrational wave packet circulation in Mn2(CO)10 driven by ultrashort
      polarized laser pulses.
AB  - The excitation of the degenerate E(1) carbonyl stretching vibrations in
      dimanganese decacarbonyl is shown to trigger wave packet circulation in the
      subspace of these two modes. On the time scale of about 5 ps, intramolecular
      anharmonic couplings do not cause appreciable disturbance, even under conditions
      where the two E(1) modes are excited by up to about two vibrational quanta each.
      The compactness of the circulating wave packet is shown to depend strongly on the
      excitation conditions, such as pulse duration and field strength. Numerical
      results for the solution of the seven-dimensional vibrational Schrodinger
      equation are obtained for a density functional theory based potential energy
      surface and using the multi-configuration time-dependent Hartree method.

PMID- 21895193
TI  - Quantum-classical simulation of electron localization in negatively charged
      methanol clusters.
AB  - A series of quantum molecular dynamics simulations have been performed to
      investigate the energetic, structural, dynamic, and spectroscopic properties of
      methanol cluster anions, [(CH(3)OH)(n)](-), (n = 50-500). Consistent with the
      inference from photo-electron imaging experiments, we find two main localization
      modes of the excess electron in equilibrated methanol clusters at ~200 K. The two
      different localization patterns have strikingly different physical properties,
      consistent with experimental observations, and are manifest in comparable cluster
      sizes to those observed. Smaller clusters (n <= 128) tend to localize the
      electron in very weakly bound, diffuse electronic states on the surface of the
      cluster, while in larger ones the electron is stabilized in solvent cavities, in
      compact interior-bound states. The interior states exhibit properties that
      largely resemble and smoothly extrapolate to those simulated for a solvated
      electron in bulk methanol. The surface electronic states of methanol cluster
      anions are significantly more weakly bound than the surface states of the anionic
      water clusters. The key source of the difference is the lack of stabilizing free
      hydroxyl groups on a relaxed methanol cluster surface. We also provide a
      mechanistic picture that illustrates the essential role of the interactions of
      the excess electron with the hydroxyl groups in the dynamic process of the
      transition of the electron from surface-bound states to interior-bound states.

PMID- 21895194
TI  - Accurate determination of the Gibbs energy of Cu-Zr melts using the thermodynamic
      integration method in Monte Carlo simulations.
AB  - The design of multicomponent alloys used in different applications based on
      specific thermo-physical properties determined experimentally or predicted from
      theoretical calculations is of major importance in many engineering applications.
      A procedure based on Monte Carlo simulations (MCS) and the thermodynamic
      integration (TI) method to improve the quality of the predicted thermodynamic
      properties calculated from classical thermodynamic calculations is presented in
      this study. The Gibbs energy function of the liquid phase of the Cu-Zr system at
      1800 K has been determined based on this approach. The internal structure of Cu
      Zr melts and amorphous alloys at different temperatures, as well as other
      physical properties were also obtained from MCS in which the phase trajectory was
      modeled by the modified embedded atom model formalism. A rigorous comparison
      between available experimental data and simulated thermo-physical properties
      obtained from our MCS is presented in this work. The modified quasichemical model
      in the pair approximation was parameterized using the internal structure data
      obtained from our MCS and the precise Gibbs energy function calculated at 1800 K
      from the TI method. The predicted activity of copper in Cu-Zr melts at 1499 K
      obtained from our thermodynamic optimization was corroborated by experimental
      data found in the literature. The validity of the amplitude of the entropy of
      mixing obtained from the in silico procedure presented in this work was analyzed
      based on the thermodynamic description of hard sphere mixtures.

PMID- 21895195
TI  - Van der Waals supercritical fluid: exact formulas for special lines.
AB  - In the framework of the van der Waals model, analytical expressions for the locus
      of extrema (ridges) for heat capacity, thermal expansion coefficient,
      compressibility, density fluctuation, and sound velocity in the supercritical
      region have been obtained. It was found that the ridges for different
      thermodynamic values virtually merge into single Widom line only at T < 1.07T(c),
      P < 1.25P(c) and become smeared at T < 2T(c), P < 5P(c), where T(c) and P(c) are
      the critical temperature and pressure. The behavior of the Batschinski lines and
      the pseudo-Gruneisen parameter gamma of a van der Waals fluid were analyzed. In
      the critical point, the van der Waals fluid has gamma = 8/3, corresponding to a
      soft sphere particle system with exponent n = 14.

PMID- 21895196
TI  - Ab initio studies of the para- and antiferroelectric structures and local
      polarized configurations in NH4H2PO4.
AB  - A study of differently polarized structures relevant to the H-bonded
      antiferroelectric (AFE) compound NH(4)H(2)PO(4) (ADP) is performed by first
      principles calculations in the framework of the density functional theory. The
      calculated structures for the AFE and paraelectric (PE) phases are found in
      general good agreement with the available experimental data. We study the
      energetics and relative stability of different polarized clusters embedded in a
      PE matrix of ADP. We find that local ferroelectric and AFE clusters are stable
      and may coexist in the PE phase, which explains the coexistence of both type of
      microregions determined by electron spin probe measurements above the AFE-PE
      transition temperature. The dependency with the O-H...O bridge length of the
      energy barrier heights for proton transfer is studied for coordinated proton
      displacements along the bridges within clusters of different sizes. This
      dependency may have implications for the geometric isotopic effects on T(c). We
      analyze Mulliken orbital and bond populations which confirm the existence of a
      charge flow within the NH(4)(+) ion, an essential fact for the stabilization of
      the AFE phase over other possible polarized structures. This charge transfer is
      correlated with the optimization of the N-H...O bridges and with distortions of
      the NH(4)(+) group.

PMID- 21895197
TI  - Nuclear magnetic resonance studies on the rotational and translational motions of
      ionic liquids composed of 1-ethyl-3-methylimidazolium cation and
      bis(trifluoromethanesulfonyl)amide and bis(fluorosulfonyl)amide anions and their
      binary systems including lithium salts.
AB  - Room temperature ionic liquids (ILs) are stable liquids composed of anions and
      cations. 1-ethyl-3-methyl-imidazolium (EMIm, EMI) is a popular and important
      cation that produces thermally stable ILs with various anions. In this study two
      amide-type anions, bis(trifluoro-methanesulfonyl)amide [N(SO(2)CF(3))(2), TFSA,
      TFSI, NTf(2), or Tf(2)N] and bis(fluorosulfonyl)amide [(N(SO(2)F)(2), FSA, or
      FSI] were investigated by multinuclear NMR spectroscopy. In addition to EMIm-TFSA
      and EMIm-FSA, lithium-salt-doped binary systems were prepared (EMIm-TFSA-Li and
      EMIm-FSA-Li). The spin-lattice relaxation times (T(1)) were measured by (1)H,
      (19)F, and (7)Li NMR spectroscopy and the correlation times of (1)H NMR,
      tau(c)(EMIm) (8 * 10(-10) to 3 * 10(-11) s) for the librational molecular motion
      of EMIm and those of (7)Li NMR, tau(c)(Li) (5 * 10(-9) to 2 * 10(-10) s) for a
      lithium jump were evaluated in the temperature range between 253 and 353 K. We
      found that the bulk viscosity (eta) versus tau(c)(EMIm) and cation diffusion
      coefficient D(EMIm) versus the rate 1/tau(c)(EMIm) have good relationships.
      Similarly, linear relations were obtained for the eta versus tau(c)(Li) and the
      lithium diffusion coefficient D(Li) versus the rate 1/tau(c)(Li). The mean one
      jump distances of Li were calculated from tau(c)(Li) and D(Li). The experimental
      values for the diffusion coefficients, ionic conductivity, viscosity, and density
      in our previous paper were analyzed by the Stokes-Einstein, Nernst-Einstein, and
      Stokes-Einstein-Debye equations for the neat and binary ILs to clarify the
      physicochemical properties and mobility of individual ions. The deviations from
      the classical equations are discussed.

PMID- 21895198
TI  - Theoretical study on vibrational circular dichroism spectra of
      tris(acetylacetonato)metal(III) complexes: anharmonic effects and low-lying
      excited states.
AB  - The open-shell density functional theory calculations with M06 exchange
      correlation functional and all-electron Douglas-Kroll second order scalar
      relativistic correction were performed to interpret the vibrational circular
      dichroism (VCD) spectra of four kinds of tris(acetylacetonato)metal(III),
      [M(III)(acac)(3)] (acac = acetylacetonato, M = Ru, Cr, Co, and Rh). It was
      deduced that the experimental spectra were well reproduced by the calculation
      with harmonic approximation in case of [Co(III)(acac)(3)] (d(6); S = 0),
      [Rh(III)(acac)(3)] (d(6); S = 0), and [Ru(III)(acac)(3)] (d(5); S = 1/2). In case
      of [Cr(III)(acac)(3)] (d(3); S = 3/2), anharmonic effects should be taken into
      account to predict the accurate vibrational frequencies of closely located modes.
      Time-dependent density functional theory calculations were performed to estimate
      the contribution of excited states in the VCD spectra. As a consequence, the
      presence of the low-lying excited states was predicted for [Ru(III)(acac)(3)]
      alone, which agreed with the experimental observation.

PMID- 21895199
TI  - Effect of high hydrostatic pressure on the dielectric relaxation in a non
      crystallizable monohydroxy alcohol in its supercooled liquid and glassy states.
AB  - The complex relative permittivity of a non-crystallizable secondary alcohol, 5
      methyl-2-hexanol, is measured over a wide range of temperatures and pressures up
      to 1750 MPa (17.5 kbar). The data at atmospheric pressure (P = 0.101 MPa) are
      analyzed in terms of three processes, and the results are in complete agreement
      with that of O. E. Kalinovskaya and J. K. Vij [J. Chem. Phys. 112, 3262 (2000)].
      Process I is of the Debye type and process II is of the Davidson-Cole type,
      whereas process III is identified as the Johari-Goldstein relaxation process. For
      pressures of ~500 MPa and higher, processes I and II are seen to merge into each
      other to form a single dominant process which unambiguously cannot be resolved
      into more than one process. The dielectric relaxation strength of process I
      decreases slightly initially with pressure and when the two processes have merged
      at elevated pressures, the total relaxation strength increases with increase in
      pressure. Process III is better resolvable at higher pressures especially above
      T(g) in the supercooled liquid state for the reason that the separation in the
      time scales between the dominant and the JG relaxation process increases at
      elevated pressures. Surprisingly we find a change in the slope in the plot of log
      tau(JG) vs. 1/T for P = 1750 MPa. The results for the relaxation time of alcohols
      are compared with the Kirkwood correlation factor, g, and it is found that higher
      is the g, lower is the relaxation time for process I, and it is more of the Debye
      type. On a reduction in g brought about by an increase in pressure at lower
      temperatures, the dominant process becomes non-Debye though extensive hydrogen
      bonding is still present. The dielectric strength of the merged processes
      increases with increase in pressure. The values of the steepness index, m = |d
      log tau/d(T(g)/T)|(T = Tg) for processes I and II are different for P = 0.1 MPa.
      However the value of m, for the composite process, which is a merger of processes
      I and II, for P = 1750 MPa is almost the same for process II at P = 0.1 MPa. From
      the results of the activation volume, activation enthalpy, and a comparison of
      the relaxation times with the g factor, we conclude that both processes I and II
      are significantly affected by hydrogen bonding and both contribute to the
      structural relaxation.

PMID- 21895200
TI  - Hard ellipsoids: analytically approaching the exact overlap distance.
AB  - Following previous work [G. Odriozola and F. de J. Guevara-Rodriguez, J. Chem.
      Phys. 134, 201103 (2011)], the replica exchange Monte Carlo technique is used to
      produce the equation of state of hard 1:5 aspect-ratio oblate ellipsoids for a
      wide density range. Here, in addition to the analytical approximation of the
      overlap distance given by Berne and Pechukas (BP) and the exact numerical
      solution of Perram and Wertheim, we tested a simple modification of the original
      BP approximation (MBP) which corrects the known T-shape mismatch of BP for all
      aspect ratios. We found that the MBP equation of state shows a very good
      quantitative agreement with the exact solution. The MBP analytical expression
      allowed us to study size effects on the previously reported results. For the
      thermodynamic limit, we estimated the exact 1:5 hard ellipsoid isotropic-nematic
      transition at the volume fraction 0.343 +/- 0.003, and the nematic-solid
      transition in the volume fraction interval (0.592 +/- 0.006)-(0.634 +/- 0.008).

PMID- 21895201
TI  - Structural transitions in hypersphere fluids: predictions of Kirkwood's
      approximation.
AB  - We use an analytic criterion for vanishing of exponential damping of correlations
      developed previously [J. Piasecki et al., J. Chem. Phys. 133, 164507 (2010)] to
      determine the threshold volume fractions for structural transitions in hard
      sphere systems in dimensions D = 3, 4, 5, and 6, proceeding from the Yvon-Born
      Green hierarchy and using the Kirkwood superposition approximation. We conclude
      that the theory does predict phase transitions in qualitative agreement with
      numerical studies. We also derive, within the superposition approximation, the
      asymptotic form of the analytic condition for occurrence of a structural
      transition in the D -> infinity limit.

PMID- 21895202
TI  - Statistical mechanics of hydrated electron recombination in liquid and
      supercritical water.
AB  - The photochemical yield of hydrated electrons as a function of temperature in
      liquid and supercritical water is treated in terms of energy fluctuations of the
      medium. The geminate pair, consisting of a positive ion and a hydrated electron,
      is regarded as a H-like atom embedded in a completely relaxed dielectric
      continuum. If the local medium energy is larger than the ionization energy of
      this atom, the electron escapes its geminate partner. By making use of the
      classical theory of energy fluctuations, escape probability is described by a
      simple explicit function, the variable of which is a combination of temperature,
      relative permittivity, and specific heat. First our earlier calculations on the
      recombination of solvated electrons, produced by ionizing radiation in a number
      of polar liquids, are improved and then the theory is compared with the
      experimental results on temperature dependent electron survival by Kratz et al.
      [S. Kratz, J. Torres-Alcan, J. Urbanek, J. Lindner, and P. Vohringer, Phys. Chem.
      Chem. Phys. 12, 12169 (2010)]. Two adjustable parameters are needed to achieve
      reasonable quantitative agreement.

PMID- 21895203
TI  - Time-dependent fluorescence in nanoconfined solvents: linear-response
      approximations and Gaussian statistics.
AB  - The time-dependent fluorescence of a model dye molecule in a nanoconfined solvent
      is used to test approximations based on the dynamic and static linear-response
      theories and the assumption of Gaussian statistics. Specifically, the results of
      nonequilibrium molecular-dynamics simulations are compared to approximate
      expressions involving time correlation functions obtained from equilibrium
      simulations. Solvation dynamics of a model diatomic dye molecule dissolved in
      acetonitrile confined in a spherical hydrophobic cavity of radius 12, 15, and 20
      A is used as the test case. Both the time-dependent fluorescence energy,
      expressed as the normalized dynamic Stokes shift, and the time-dependent position
      of the dye molecule after excitation are examined. While the dynamic linear
      response approximation fails to describe key aspects of the solvation dynamics,
      assuming Gaussian statistics reproduces the full nonequilibrium simulations well.
      The implications of these results are discussed.

PMID- 21895204
TI  - Polymorphism of dense, hot oxygen.
AB  - The phase diagram and polymorphism of oxygen at high pressures and temperatures
      are of great interest to condensed matter and earth science. X-ray diffraction
      and Raman spectroscopy of oxygen using laser and resistively heated diamond anvil
      cells reveal that the molecular high-pressure phase epsilon-O(2), which consists
      of (O(2))(4) clusters, reversibly transforms in the pressure range of 44 to 90
      GPa and temperatures near 1000 K to a new phase with higher symmetry. The data
      suggest that this new phase (eta') is isostructural to a phase eta reported
      previously at lower pressures and temperatures, but differs from it in the P-T
      range of stability and type of intermolecular association. The melting curve
      increases monotonically up to the maximum pressures studied (~60 GPa). The
      structure factor of the fluid measured as a function of pressure to 58 GPa shows
      continuous changes toward molecular dissociation.

PMID- 21895205
TI  - Structure, dynamics, and thermodynamics of a family of potentials with tunable
      softness.
AB  - We investigate numerically the structure, thermodynamics, and relaxation behavior
      of a family of (n, 6) Lennard-Jones-like glass-forming binary mixtures
      interacting via pair potentials with variable softness, fixed well depth, and
      fixed well depth location. These constraints give rise to progressively more
      negative attractive tails upon softening, for separations greater than the
      potential energy minimum. Over the range of conditions examined, we find only
      modest dependence of structure on softness. In contrast, decreasing the repulsive
      exponent from n=12 to n=7 causes the diffusivity to increase by as much as two
      orders of magnitude at fixed temperature and density, and produces mechanically
      stable packings (inherent structures) with cohesive energies that are, on
      average, ~1.7 well depths per particle larger than for the corresponding Lennard
      Jones (n=12) case. The softer liquids have markedly higher entropies and lower
      Kauzmann temperatures than their Lennard-Jones (n=12) counterparts, and they
      remain diffusive down to appreciably lower temperatures. We find that softening
      leads to a modest increase in fragility.

PMID- 21895206
TI  - Electric field inside a "Rossky cavity" in uniformly polarized water.
AB  - Electric field produced inside a solute by a uniformly polarized liquid is
      strongly affected by dipolar polarization of the liquid at the interface. We
      show, by numerical simulations, that the electric "cavity" field inside a
      hydrated non-polar solute does not follow the predictions of standard Maxwell's
      electrostatics of dielectrics. Instead, the field inside the solute tends, with
      increasing solute size, to the limit predicted by the Lorentz virtual cavity. The
      standard paradigm fails because of its reliance on the surface charge density at
      the dielectric interface determined by the boundary conditions of the Maxwell
      dielectric. The interface of a polar liquid instead carries a preferential in
      plane orientation of the surface dipoles thus producing virtually no surface
      charge. The resulting boundary conditions for electrostatic problems differ from
      the traditional recipes, affecting the microscopic and macroscopic fields based
      on them. We show that relatively small differences in cavity fields propagate
      into significant differences in the dielectric constant of an ideal mixture. The
      slope of the dielectric increment of the mixture versus the solute concentration
      depends strongly on which polarization scenario at the interface is realized. A
      much steeper slope found in the case of Lorentz interfacial polarization also
      implies a higher free energy penalty for polarizing such mixtures.

PMID- 21895207
TI  - Thermodynamics and diffusion in size-symmetric and asymmetric dense electrolytes.
AB  - MD simulation results for model size-symmetric and asymmetric electrolytes at
      high densities and temperatures (well outside the liquid-gas coexistence region)
      are generated and analyzed focusing on thermodynamic and diffusion properties. An
      extension of the mean spherical approximation for electrolytes originally derived
      for charged hard sphere fluids is adapted to these systems by exploiting the
      separation of short range and Coulomb interaction contributions intrinsic to
      these theoretical models and is found to perform well for predicting equation of
      state quantities. The diffusion coefficients of these electrolytes can also be
      reasonably well predicted using entropy scaling ideas suitably adapted to charged
      systems and mixtures. Thus, this approach may provide an avenue for studying
      dense electrolytes or complex molecular systems containing charged species at
      high pressures and temperatures.

PMID- 21895208
TI  - Interaction of charge carriers with lattice and molecular phonons in crystalline
      pentacene.
AB  - The computational protocol we have developed for the calculation of local
      (Holstein) and non-local (Peierls) carrier-phonon coupling in molecular organic
      semiconductors is applied to both the low temperature and high temperature bulk
      crystalline phases of pentacene. The electronic structure is calculated by the
      semimpirical INDO/S (Intermediate Neglect of Differential Overlap with
      Spectroscopic parametrization) method. In the phonon description, the rigid
      molecule approximation is removed, allowing mixing of low-frequency intra
      molecular modes with inter-molecular (lattice) phonons. A clear distinction
      remains between the low-frequency phonons, which essentially modulate the
      transfer integral from a molecule to another (Peierls coupling), and the high
      frequency intra-molecular phonons, which modulate the on-site energy (Holstein
      coupling). The results of calculation agree well with the values extracted from
      experiment. The comparison with similar calculations made for rubrene allows us
      to discuss the implications for the current models of mobility.

PMID- 21895209
TI  - Charging energy and barrier height of pentacene on Au(111): a local-orbital
      hybrid-functional density functional theory approach.
AB  - We analyze the pentacene/Au(111) interface by means of density functional theory
      (DFT) calculations using a new hybrid functional; in our approach we introduce,
      in a local-orbital formulation of DFT, a hybrid exchange potential, and combine
      it with a calculation of the molecule charging energy to properly describe the
      transport energy gap of pentacene on Au(111). Van der Waals forces are taken into
      account to obtain the adsorption geometry. Interface dipole potentials are also
      calculated; it is shown that the metal/pentacene energy level alignment is
      determined by the potential induced by the charge transfer between the metal
      surface and the organic material, as described by the induced density of
      interface states model. Our results compare well with the experimental data.

PMID- 21895210
TI  - Extension of the Steele 10-4-3 potential for adsorption calculations in
      cylindrical, spherical, and other pore geometries.
AB  - Simplified fluid-substrate interaction models derived from the Lennard-Jones
      potential are widely used in the simulation of gas physisorption phenomena. In
      this paper, we reinterpret the well known Steele 10-4-3 potential for a gas
      molecule interacting with a planar surface, and use the resultant scheme to
      derive new potentials for cylindrical and spherical pore geometries. These new
      potentials correctly recover the Steele result in the limit of infinite pore
      radius, a useful improvement over existing models. We demonstrate the new
      cylindrical Steele 10-4-3 potential in calculations of argon adsorption via fluid
      density functional theory. This potential yields markedly different adsorption
      behavior than existing cylindrical potentials, which follow from small but
      significant differences in both the strength and the shape of the fluid-surface
      interaction. These differences cannot be fully reconciled simply by
      reparameterizing (scaling) the existing models; the new potential is more
      realistic in design, and is especially to be preferred in studies where
      comparison with planar substrates is made. Finally, we discuss extensions of this
      approach to more complicated pore geometries, yielding a family of Steele-like
      potentials that all satisfy the correct planar limit.

PMID- 21895211
TI  - Self-consistent meta-generalized gradient approximation study of adsorption of
      aromatic molecules on noble metal surfaces.
AB  - The adsorption of benzene, pyridine, and two nucleobases on the Au(111) surface
      has been investigated using a fully relaxed, self-consistent meta-generalized
      gradient approximation (meta-GGA) density functional theory setup with the M06-L
      functional. The meta-GGA based molecule-surface separations are shortened and the
      adsorption bond strengths of the molecules are greatly improved over the
      virtually non-interacting results obtained when using a plain GGA exchange
      correlation functional. The nucleobases containing oxygen atoms show higher
      corrugation with adsorption site and orientation than the other aromatic
      molecules considered. The adsorption of pentacene is studied on Au, Ag, and Cu
      surfaces. In agreement with experiment, the adsorption energies are found to
      increase with decreasing nobleness, but the dependency is underestimated. We
      point out how the kinetic energy density can discriminate between covalent and
      non-covalent bonding regions of orbital overlap.

PMID- 21895212
TI  - Thermodynamic stability of a bi-layer of copper nitride on Cu(100) surface.
AB  - Ultrathin insulating films composed of a few atomic layers are being extensively
      used for controlling the electronic coupling of nanostructures deposited on a
      substrate. Ultrathin film, for example, a single layer of Cu(2)N deposited on a
      Cu(100) surface (known as Cu(2)N/Cu(100) surface) has been used to determine the
      spectral properties of nanomagnets using scanning tunneling spectroscopy.
      However, recent experiments that measure spin relaxation times in a single atom
      suggest that the single layer of Cu(2)N does not provide efficient electronic
      decoupling. In this work, we study the thermodynamic stability of a bi-layer of
      copper nitride on the Cu(100) surface. We calculate adsorption and co-adsorption
      energies of Cu and N as a function of their concentration on the Cu(2)N/Cu(100)
      surface using density functional theory. We find that the adsorption and co
      adsorption energies of Cu and N on the Cu(2)N/Cu(100) surface are of the order of
      a few eV. This suggests that the bi-layer of copper nitride is thermodynamically
      stable on the Cu(100) surface. We also find that the work function of N-adsorbed
      Cu(2)N/Cu(100) increases with the N concentration, suggesting a better insulating
      character of the bi-layer of copper nitride on the Cu(100) surface.

PMID- 21895213
TI  - Temperature-dependent growth shapes of Ni nanoclusters on NiAl(110).
AB  - Scanning tunneling microscopy studies reveal that two-dimensional nanoscale Ni
      islands formed by deposition of Ni on NiAl(110) between 200-400 K exhibit far
      from-equilibrium growth shapes which change systematically with temperature.
      Island structure reflects the two types of adsorption sites available for Ni
      adatoms, and island shapes are controlled by the details of adatom diffusion
      along island edges accounting for numerous local configurations. The temperature
      dependence of the island shapes is captured and elucidated by kinetic Monte Carlo
      simulation of a realistic atomistic-level multisite lattice-gas model
      incorporating precise diffusion barriers. These barriers are obtained by
      utilizing density functional theory to probe energetics not just at adsorption
      sites but also at transition states for diffusion. This success demonstrates a
      capability for predictive atomistic-level modeling of nanocluster formation and
      shape selection in systems that have a high level of energetic and kinetic
      complexity.

PMID- 21895214
TI  - Exploring parameter space effects on structure-property relationships of
      surfactants at liquid-liquid interfaces.
AB  - The ubiquitous use of surfactants in commercial and industrial applications has
      led to many experimental, theoretical, and simulation based studies. These
      efforts seek to provide a molecular level understanding of the effects on
      structuring behavior and the corresponding impacts on observable properties
      (e.g., interfacial tension). With such physical detail, targeted system design
      can be improved over typical techniques of observational trends and
      phenomenological correlations by taking advantage of predictive system response.
      This research provides a systematic study of part of the broad parameter space
      effects on equilibrium microstructure and interfacial properties of amphiphiles
      at a liquid-liquid interface using the interfacial statistical associating fluid
      theory density functional theory as a molecular model for the system from the
      bulk to the interface. Insights into the molecular level physics and
      thermodynamics governing the system behavior are discussed as they relate to both
      predictions qualitatively consistent with experimental observations and
      extensions beyond currently available studies.

PMID- 21895215
TI  - On the formation of hydrogen gas on copper in anoxic water.
AB  - Hydrogen gas has been detected in a closed system containing copper and pure
      anoxic water [P. Szakalos, G. Hultquist, and G. Wikmark, Electrochem. Solid-State
      Lett. 10, C63 (2007) and G. Hultquist, P. Szakalos, M. Graham, A. Belonoshko, G.
      Sproule, L. Grasjo, P. Dorogokupets, B. Danilov, T. Aastrup, G. Wikmark, G.
      Chuah, J. Eriksson, and A. Rosengren, Catal. Lett. 132, 311 (2009)]. Although
      bulk corrosion into any of the known phases of copper is thermodynamically
      forbidden, the present paper shows how surface reactions lead to the formation of
      hydrogen gas in limited amounts. While water cleavage on copper has been reported
      and investigated before, formation of molecular hydrogen at a single-crystal
      Cu[100] surface is here explored using density functional theory and transition
      state theory. It is found that although solvent catalysis seems possible, the
      fastest route to the formation of molecular hydrogen is the direct combination of
      hydrogen atoms on the copper surface. The activation free energy
      (DeltaG(s)(?)(f)) of hydrogen formation in condensed phase is 0.70 eV, which
      corresponds to a rate constant of 10 s(-1) at 298.15 K, i.e., a relatively rapid
      process. It is estimated that at least 2.4 ng hydrogen gas could form per cm(2)
      on a perfect copper surface.

PMID- 21895216
TI  - Colloidal interactions mediated by end-adsorbing polymer-like micelles.
AB  - We derive a statistical mechanical model for colloidal interactions mediated by
      polymer-like micelles (PLMs) that adsorb at the colloid surface. The model
      considers the end-adsorption and reversible scission of ideal chains, and is
      based on experimentally measurable parameters relevant to PLMs. The model
      predicts interparticle attractions due to micellar bridging that are stronger and
      longer-range than those encountered in ordinary telechelic polymers. Mapping the
      analytical potential onto the more familiar Double Yukawa potential allows, for
      the first time, accurate, a priori prediction of suspension microstructure and
      phase behavior when compared to experimental data for model nanoparticles
      dispersed in wormlike micelles over a range of solution conditions.

PMID- 21895217
TI  - Renormalized one-loop theory of correlations in disordered diblock copolymers.
AB  - A renormalized one-loop (ROL) theory developed in previous work [P. Grzywacz, J.
      Qin, and D. C. Morse, Phys. Rev E. 76, 061802 (2007)] is used to calculate
      corrections to the random phase approximation (RPA) for the structure factor S(q)
      in disordered diblock copolymer melts. Predictions are given for the peak
      intensity S(q*), peak position q*, and single-chain statistics for symmetric and
      asymmetric copolymers as functions of chi(e)N, where chi(e) is an effective Flory
      Huggins interaction parameter and N is the degree of polymerization. The ROL and
      Fredrickson-Helfand (FH) theories are found to yield asymptotically equivalent
      results for the dependence of the peak intensity S(q*) upon chi(e)N for symmetric
      diblock copolymers in the limit of strong scattering, or large chi(e)N, but to
      yield qualitatively different predictions for symmetric copolymers far from the
      ODT and for asymmetric copolymers. The ROL theory predicts a suppression of S(q*)
      and a decrease of q* for large values of chi(e)N, relative to the RPA
      predictions, but an enhancement of S(q*) and an increase in q* for small chi(e)N.
      The decrease in q* near the ODT is shown to be unrelated to any change in single
      chain statistics, and to be a result of inter-molecular correlations. Conversely,
      the predicted increase in q* at small values of chi(e)N is a direct result of non
      Gaussian single-chain statistics.

PMID- 21895218
TI  - Thermal rupture of linear alternate copolymers: a molecular dynamics study.
AB  - The thermal rupture of a linear alternating copolymer fixed at one end and pulled
      by a constant force at the other end has been studied using molecular dynamics
      simulation. The dependence of the first breakage time distribution on the mass
      ratio of the constituent beads has been studied. The Arrhenian nature of the
      scission process has been confirmed and an estimate of the effective energy
      barrier has been made.

PMID- 21895219
TI  - Pairwise additivity of energy components in protein-ligand binding: the HIV II
      protease-Indinavir case.
AB  - An energy expansion (binding energy decomposition into n-body interaction terms
      for n >= 2) to express the receptor-ligand binding energy for the fragmented HIV
      II protease-Indinavir system is described to address the role of cooperativity in
      ligand binding. The outcome of this energy expansion is compared to the total
      receptor-ligand binding energy at the Hartree-Fock, density functional theory,
      and semiempirical levels of theory. We find that the sum of the pairwise
      interaction energies approximates the total binding energy to ~82% for HF and to
      >95% for both the M06-L density functional and PM6-DH2 semiempirical method. The
      contribution of the three-body interactions amounts to 18.7%, 3.8%, and 1.4% for
      HF, M06-L, and PM6-DH2, respectively. We find that the expansion can be safely
      truncated after n=3. That is, the contribution of the interactions involving more
      than three parties to the total binding energy of Indinavir to the HIV II
      protease receptor is negligible. Overall, we find that the two-body terms
      represent a good approximation to the total binding energy of the system, which
      points to pairwise additivity in the present case. This basic principle of
      pairwise additivity is utilized in fragment-based drug design approaches and our
      results support its continued use. The present results can also aid in the
      validation of non-bonded terms contained within common force fields and in the
      correction of systematic errors in physics-based score functions.

PMID- 21895220
TI  - Effects of surface interactions on peptide aggregate morphology.
AB  - The formation of peptide aggregates mediated by an attractive surface is
      investigated using replica exchange molecular dynamics simulations with a coarse
      grained peptide representation. In the absence of a surface, the peptides exhibit
      a range of aggregate morphologies, including amorphous aggregates, beta-barrels
      and multi-layered fibrils, depending on the chiral stiffness of the chain (a
      measure of its beta-sheet propensity). In contrast, aggregate morphology in the
      presence of an attractive surface depends more on surface attraction than on
      peptide chain stiffness, with the surface favoring fibrillar structures. Peptide
      peptide interactions couple to peptide-surface interactions cooperatively to
      affect the assembly process both qualitatively (in terms of aggregate morphology)
      and quantitatively (in terms of transition temperature and transition sharpness).
      The frequency of ordered fibrillar aggregates, the surface binding transition
      temperature, and the sharpness of the binding transition all increase with both
      surface attraction and chain stiffness.

PMID- 21895221
TI  - Electrostatics and aggregation: how charge can turn a crystal into a gel.
AB  - The crystallization of proteins or colloids is often hindered by the appearance
      of aggregates of low fractal dimension called gels. Here we study the effect of
      electrostatics upon crystal and gel formation using an analytic model of hard
      spheres bearing point charges and short range attractive interactions. We find
      that the chief electrostatic free energy cost of forming assemblies comes from
      the entropic loss of counterions that render assemblies charge-neutral. Because
      there exists more accessible volume for these counterions around an open gel than
      a dense crystal, there exists an electrostatic entropic driving force favoring
      the gel over the crystal. This driving force increases with increasing sphere
      charge, but can be counteracted by increasing counterion concentration. We show
      that these effects cannot be fully captured by pairwise-additive macroion
      interactions of the kind often used in simulations, and we show where on the
      phase diagram to go in order to suppress gel formation.

PMID- 21895222
TI  - Some aspects of the protein folding problem examined in one-dimensional systems.
AB  - Some concepts, such as energy landscape, Gibbs energy landscape, and
      cooperativity, frequently used in the theory of protein folding, are examined
      exactly in one-dimensional systems. It is shown that much of the confusion that
      exists regarding these, and other concepts arise from the misinterpretation of
      Anfinsen's thermodynamic hypothesis.

PMID- 21895223
TI  - Thermal and mechanical denaturation properties of a DNA model with three sites
      per nucleotide.
AB  - In this paper, we show that the coarse grain model for DNA, which has been
      proposed recently by Knotts et al. [J. Chem. Phys. 126, 084901 (2007)], can be
      adapted to describe the thermal and mechanical denaturation of long DNA sequences
      by adjusting slightly the base pairing contribution. The adjusted model leads to
      (i) critical temperatures for long homogeneous sequences that are in good
      agreement with both experimental ones and those obtained from statistical models,
      (ii) a realistic step-like denaturation behaviour for long inhomogeneous
      sequences, and (iii) critical forces at ambient temperature of the order of 10
      pN, close to measured values. The adjusted model furthermore supports the
      conclusion that the thermal denaturation of long homogeneous sequences
      corresponds to a first-order phase transition and yields a critical exponent for
      the critical force equal to sigma = 0.70. This model is both geometrically and
      energetically realistic, in the sense that the helical structure and the grooves,
      where most proteins bind, are satisfactorily reproduced, while the energy and the
      force required to break a base pair lie in the expected range. It therefore
      represents a promising tool for studying the dynamics of DNA-protein specific
      interactions at an unprecedented detail level.

PMID- 21895224
TI  - Transfer matrix approach to the hydrogen-bonding in cellulose Ialpha fibrils
      describes the recalcitrance to thermal deconstruction.
AB  - Cellulosic biomass has the potential to serve as a major renewable energy source.
      However, its strong recalcitrance to degradation hampers its large-scale use in
      biofuel production. To overcome this problem, a detailed understanding of the
      origins of the recalcitrance is required. One main biophysical phenomenon leading
      to the recalcitrance is the high structural ordering of natural cellulose
      fibrils, that arises largely from an extensive hydrogen-bond network between and
      within cellulose polymers. Here, we present a lattice-based model of cellulose
      I(alpha), one of the two major natural forms, at the resolution of explicit
      hydrogen bonds. The partition function and thermodynamic properties are evaluated
      using the transfer matrix method. Two competing hydrogen-bond patterns are found.
      This plasticity of the hydrogen-bond network leads to an entropic contribution
      stabilizing the crystalline fibril at intermediate temperatures. At these
      temperatures, an enhanced probability of bonding between the individual cellulose
      chains gives rise to increased resistance of the entire cellulose fibril to
      degradation, before the final disassembly temperature is reached. The results are
      consistent with the available crystallographic and IR spectroscopic experiments
      on the thermostability of cellulose I(alpha).

PMID- 21895225
TI  - Note: extraction of hydrogen bond thermodynamic properties of water from
      dielectric constant and relaxation time data.

PMID- 21895226
TI  - Invited article: The coherent optical laser beam recombination technique
      (COLBERT) spectrometer: coherent multidimensional spectroscopy made easier.
AB  - We have developed an efficient spectrometer capable of performing a wide variety
      of coherent multidimensional measurements at optical wavelengths. The two major
      components of the largely automated device are a spatial beam shaper which
      controls the beam geometry and a spatiotemporal pulse shaper which controls the
      temporal waveform of the femtosecond pulse in each beam. We describe how to
      construct, calibrate, and operate the device, and we discuss its limitations. We
      use the exciton states of a semiconductor nanostructure as a working example. A
      series of complex multidimensional spectra-displayed in amplitude and real parts
      reveals increasingly intricate correlations among the excitons.

PMID- 21895227
TI  - Fabrication of silver tips for scanning tunneling microscope induced
      luminescence.
AB  - We describe a reliable fabrication procedure of silver tips for scanning
      tunneling microscope (STM) induced luminescence experiments. The tip was first
      etched electrochemically to yield a sharp cone shape using selected electrolyte
      solutions and then sputter cleaned in ultrahigh vacuum to remove surface
      oxidation. The tip status, in particular the tip induced plasmon mode and its
      emission intensity, can be further tuned through field emission and voltage
      pulse. The quality of silver tips thus fabricated not only offers atomically
      resolved STM imaging, but more importantly, also allows us to perform challenging
      "color" photon mapping with emission spectra taken at each pixel simultaneously
      during the STM scan under relatively small tunnel currents and relatively short
      exposure time.

PMID- 21895228
TI  - Dual-trap optical tweezers with real-time force clamp control.
AB  - Single molecule force clamp experiments are widely used to investigate how
      enzymes, molecular motors, and other molecular mechanisms work. We developed a
      dual-trap optical tweezers instrument with real-time (200 kHz update rate) force
      clamp control that can exert 0-100 pN forces on trapped beads. A model for force
      clamp experiments in the dumbbell-geometry is presented. We observe good
      agreement between predicted and observed power spectra of bead position and force
      fluctuations. The model can be used to predict and optimize the dynamics of real
      time force clamp optical tweezers instruments. The results from a proof-of
      principle experiment in which lambda exonuclease converts a double-stranded DNA
      tether, held at constant tension, into its single-stranded form, show that the
      developed instrument is suitable for experiments in single molecule biology.

PMID- 21895229
TI  - High resolution extreme ultraviolet spectrometer for an electron beam ion trap.
AB  - An extreme ultraviolet spectrometer has been developed for spectroscopic studies
      of highly charged ions with an electron beam ion trap. It has a slit-less
      configuration with a spherical varied-line-spacing grating that provides a flat
      focal plane for grazing incidence light. Alternative use of two different
      gratings enables us to cover the wavelength range 1-25 nm. Test observations with
      the Tokyo electron beam ion trap demonstrate the high performance of the present
      spectrometer such as a resolving power of above 1000.

PMID- 21895231
TI  - Interface for time-resolved electrochemical infrared microspectroscopy using
      synchrotron infrared radiation.
AB  - A description of a coupled electrochemical and spectrometer interface using
      synchrotron infrared radiation is provided. The interface described allows for
      the precise and accurate timing needed for time-resolved IR spectroscopic studies
      of electrochemical systems. The overall interface uses a series of transistor
      transistor logic trigger signals generated from the commercial FTIR spectrometer
      to regulate the recording of control, electrochemical, and IR signals with
      reproducible and adjustable timing. The instrument has been tested using a thin
      layer electrochemical cell with synchrotron light focused through microscope
      optics. The time-resolved response of the benzoquinone/dihydroxybenzoquinone
      redox couple is illustrated as an example of the instrument's capability.

PMID- 21895230
TI  - A combined small- and wide-angle x-ray scattering detector for measurements on
      reactive systems.
AB  - A detector with high dynamic range designed for combined small- and wide-angle x
      ray scattering experiments has been developed. It allows measurements on single
      events and reactive systems, such as particle formation in flames and evaporation
      of levitating drops. The detector consists of 26 channels covering a region from
      0.5 degrees  to 60 degrees  and it provides continuous monitoring of the sampled
      signal without readout dead time. The time resolution for fast single events is
      about 40 MUs and for substances undergoing slower dynamics, the time resolution
      is set to 0.1 or 1 s with hours of continuous sampling. The detector has been
      used to measure soot particle formation in a flame, burning magnesium and
      evaporation of a toluene drop in a levitator. The results show that the detector
      can be used for many different applications with good outcomes and large
      potential.

PMID- 21895232
TI  - High resolution 3D gas-jet characterization.
AB  - We present a tomographic characterization of gas jets employed for high-intensity
      laser-plasma interaction experiments where the shape can be non-symmetrically.
      With a Mach-Zehnder interferometer we measured the phase shift for different
      directions through the neutral density distribution of the gas jet. From the
      recorded interferograms it is possible to retrieve 3-dimensional neutral density
      distributions by tomographic reconstruction based on the filtered back
      projections. We report on criteria for the smallest number of recorded
      interferograms as well as a comparison with the widely used phase retrieval based
      on an Abel inversion. As an example for the performance of our approach, we
      present the characterization of nozzles with rectangular openings or gas jets
      with shock waves. With our setup we obtained a spatial resolution of less than 60
      MUm for an Argon density as low as 2 * 10(17) cm(-3).

PMID- 21895233
TI  - An LIF characterization of supersonic BO (X2Sigma+) and CN (X2Sigma+) radical
      sources for crossed beam studies.
AB  - Various ablation sources generating supersonic boron monoxide (BO; X(2)Sigma(+))
      radical beams utilizing oxygen (O(2)), carbon dioxide (CO(2)), methanol
      (CH(3)OH), and water (H(2)O) as seeding gases were characterized in a crossed
      molecular beams setup by mass resolved time-of-flight spectroscopy and
      spectroscopically via laser induced fluorescence. Intensities of the sources as
      well as rovibrational energy distributions were analyzed. The molecular oxygen
      source was found to produce excessive amount of an unwanted BO(2) byproduct.
      Internal vibrational energy of boron monoxide generated in the water and methanol
      sources was too high to be considered for the study of dynamics of ground state
      radicals. The best combination of intensity, purity, and low internal energy was
      found in the carbon dioxide source to generate boron monoxide. We successfully
      tested the boron monoxide (BO; X(2)Sigma(+)) radical beam source in crossed beams
      reactions with acetylene (C(2)H(2)) and ethylene (C(2)H(4)). The source was also
      compared with supersonic beams of the isoelectronic cyano (CN; X(2)Sigma(+))
      radical.

PMID- 21895234
TI  - Creation of arbitrary spectra with an acousto-optic modulator and an injection
      locked diode laser.
AB  - We use a double-passed acousto-optic modulator (AOM), driven by an arbitrary
      waveform generator to produce multiple frequency components for a laser with
      arbitrary frequency spacings. A programmed sequence containing various sections
      of radio-frequency sinusoidal signal at different frequency is applied to drive
      the AOM. The diffracted light is used to injection-lock a diode laser. The
      combined techniques allow us to generate the multi-line spectra for the diode
      laser with arbitrary frequency spacings in the range of 100 MHz at a relatively
      high output power of 80 mW and a small power variation of 2%. Such a light source
      can be used in the application for laser cooling of molecules.

PMID- 21895235
TI  - High spectral resolution, real-time, Raman spectroscopy in shock compression
      experiments.
AB  - The use of Raman measurements to examine molecular changes associated with shock
      induced structural and chemical changes in condensed materials often poses two
      challenging requirements: high spectral resolution and significantly reduced
      background light. Here, we describe an experimental method that addresses these
      requirements and provides better quality data than the time resolved approach
      used previously. Representative measurements are presented for shock compression
      of two energetic crystals: pentaerythritol tetranitrate and cyclotrimethylene
      trinitramine. The high spectral resolution data have provided insight into
      molecular changes that could not be obtained from lower-resolution, time-resolved
      methods.

PMID- 21895236
TI  - Offset phase locking of noisy diode lasers aided by frequency division.
AB  - For heterodyne phase locking, frequency division of the beat note between two
      oscillators can improve the reliability of the phase lock and the quality of the
      phase synchronization. Frequency division can also reduce the size, weight,
      power, and cost of the instrument by excluding the microwave synthesizer from the
      control loop when the heterodyne offset frequency is large (5 to 10 GHz). We have
      experimentally tested the use of a frequency divider in an optical phase-lock
      loop and compared the achieved level of residual phase fluctuations between two
      diode lasers with that achieved without the use of a frequency divider. The two
      methods achieve comparable phase stability provided that sufficient loop gain is
      maintained after frequency division to preserve the required bandwidth. We have
      also numerically analyzed the noise properties and internal dynamics of phase
      locked loops subjected to a high level of phase fluctuations, and our modeling
      confirms the expected benefits of having an in-loop frequency divider.

PMID- 21895237
TI  - Increasing the energy dynamic range of solid-state nuclear track detectors using
      multiple surfaces.
AB  - Solid-state nuclear track detectors, such as CR-39, are widely used in physics
      and in many inertial confinement fusion (ICF) experiments. In the ICF
      experiments, the particles of interest, such as D(3)He-protons, have ranges of
      order of the detector thickness. In this case, the dynamic range of the detector
      can be extended by recording data on both the front and back sides of the
      detector. Higher energy particles which are undetectable on the front surface can
      then be measured on the back of the detector. Studies of track formation under
      the conditions on the front and back of the detector reveal significant
      differences. Distinct front and back energy calibrations of CR-39 are therefore
      necessary and are presented for protons. Utilizing multiple surfaces with
      additional calibrations can extend the range of detectable energies on a single
      piece of CR-39 by up to 7-8 MeV. The track formation process is explored with a
      Monte Carlo code, which shows that the track formation difference between front
      and back is due to the non-uniform ion energy deposition in matter.

PMID- 21895238
TI  - An ultra-low energy (30-200 eV) ion-atomic beam source for ion-beam-assisted
      deposition in ultrahigh vacuum.
AB  - The paper describes the design and construction of an ion-atomic beam source with
      an optimized generation of ions for ion-beam-assisted deposition under ultrahigh
      vacuum (UHV) conditions. The source combines an effusion cell and an electron
      impact ion source and produces ion beams with ultra-low energies in the range
      from 30 eV to 200 eV. Decreasing ion beam energy to hyperthermal values (~10(1)
      eV) without loosing optimum ionization conditions has been mainly achieved by the
      incorporation of an ionization chamber with a grid transparent enough for
      electron and ion beams. In this way the energy and current density of nitrogen
      ion beams in the order of 10(1) eV and 10(1) nA/cm(2), respectively, have been
      achieved. The source is capable of growing ultrathin layers or nanostructures at
      ultra-low energies with a growth rate of several MLs/h. The ion-atomic beam
      source will be preferentially applied for the synthesis of GaN under UHV
      conditions.

PMID- 21895239
TI  - A Thomson parabola ion imaging spectrometer designed to probe relativistic
      intensity ionization dynamics of nanoclusters.
AB  - Conventional techniques of probing ionization dynamics at relativistic
      intensities for extended target systems such as clusters are difficult both due
      to problems of achieving good charge resolution and signal integration over the
      focal volume. Simultaneous measurement of arrival time, necessary for these
      systems, has normally involved complicated methods. We designed and developed a
      Thomson parabola imaging spectrometer that overcomes these problems. Intensity
      sampling method evolved in this report is proved to be mandatory for probing
      ionization dynamics of clusters at relativistic intensities. We use this method
      to measure charge resolved kinetic energy spectra of argon nanoclusters at
      intensities of 4 * 10(18) W cm(-2).

PMID- 21895240
TI  - Profiling of barrier capacitance and spreading resistance using a transient
      linearly increasing voltage technique.
AB  - A technique for the combined measurement of barrier capacitance and spreading
      resistance profiles using a linearly increasing voltage pulse is presented. The
      technique is based on the measurement and analysis of current transients, due to
      the barrier and diffusion capacitance, and the spreading resistance, between a
      needle probe and sample. To control the impact of deep traps in the barrier
      capacitance, a steady state bias illumination with infrared light was employed.
      Measurements of the spreading resistance and barrier capacitance profiles using a
      stepwise positioned probe on cross sectioned silicon pin diodes and pnp
      structures are presented.

PMID- 21895241
TI  - A solid-state Marx generator driven Einzel lens chopper.
AB  - A new type of pulse chopper called an Einzel lens chopper is described. An Einzel
      lens placed immediately after an electron cyclotron resonance ion source is
      driven by high-voltage pulses generated by a newly developed solid-state Marx
      generator. A rectangular negative barrier pulse-voltage is controlled in time,
      and the barrier pulse is turned on only when a beam pulse is required. The
      results of successful experiments are reported herein.

PMID- 21895242
TI  - Development of a real time monitor and multivariate method for long term
      diagnostics of atmospheric pressure dielectric barrier discharges: application to
      He, He/N2, and He/O2 discharges.
AB  - In this paper we present the development and application of a real time
      atmospheric pressure discharge monitoring diagnostic. The software based
      diagnostic is designed to extract latent electrical and optical information
      associated with the operation of an atmospheric pressure dielectric barrier
      discharge (APDBD) over long time scales. Given that little is known about long
      term temporal effects in such discharges, the diagnostic methodology is applied
      to the monitoring of an APDBD in helium and helium with both 0.1% nitrogen and
      0.1% oxygen gas admixtures over periods of tens of minutes. Given the large
      datasets associated with the experiments, it is shown that this process is much
      expedited through the novel application of multivariate correlations between the
      electrical and optical parameters of the corresponding chemistries which, in
      turn, facilitates comparisons between each individual chemistry also. The results
      of these studies show that the electrical and optical parameters of the discharge
      in helium and upon the addition of gas admixtures evolve over time scales far
      longer than the gas residence time and have been compared to current modelling
      works. It is envisaged that the diagnostic together with the application of
      multivariate correlations will be applied to rapid system identification and
      prototyping in both experimental and industrial APDBD systems in the future.

PMID- 21895243
TI  - New signal processing technique for density profile reconstruction using
      reflectometry.
AB  - Reflectometry profile measurement requires an accurate determination of the
      plasma reflected signal. Along with a good resolution and a high signal to noise
      ratio of the phase measurement, adequate data analysis is required. A new data
      processing based on time-frequency tomographic representation is used. It
      provides a clearer separation between multiple components and improves isolation
      of the relevant signals. In this paper, this data processing technique is applied
      to two sets of signals coming from two different reflectometer devices used on
      the Tore Supra tokamak. For the standard density profile reflectometry, it
      improves the initialization process and its reliability, providing a more
      accurate profile determination in the far scrape-off layer with density
      measurements as low as 10(16) m(-1). For a second reflectometer, which provides
      measurements in front of a lower hybrid launcher, this method improves the
      separation of the relevant plasma signal from multi-reflection processes due to
      the proximity of the plasma.

PMID- 21895244
TI  - Tritium plasma experiment: parameters and potentials for fusion plasma-wall
      interaction studies.
AB  - The tritium plasma experiment (TPE) is a unique facility devoted to experiments
      on the behavior of deuterium/tritium in toxic (e.g., beryllium) and radioactive
      materials for fusion plasma-wall interaction studies. A Langmuir probe was added
      to the system to characterize the plasma conditions in TPE. With this new
      diagnostic, we found the achievable electron temperature ranged from 5.0 to 10.0
      eV, the electron density varied from 5.0 * 10(16) to 2.5 * 10(18) m(-3), and the
      ion flux density varied between 5.0 * 10(20) to 2.5 * 10(22) m(-2) s(-1) along
      the centerline of the plasma. A comparison of these plasma parameters with the
      conditions expected for the plasma facing components (PFCs) in ITER shows that
      TPE is capable of achieving most (~800 m(2) of 850 m(2) total PFCs area) of the
      expected ion flux density and electron density conditions.

PMID- 21895245
TI  - Compact device for cleaning scanner-mounted scanning tunneling microscope tips
      using electron bombardment.
AB  - Most scanning probe techniques rely on the assumption that both sample and tip
      are free from adsorbates, residues, and oxide not deposited intentionally.
      Getting a clean sample surface can be readily accomplished by applying ion
      sputtering and subsequent annealing, whereas finding an adequate treatment for
      tips is much more complicated. The method of choice would effectively desorb
      undesired compounds without reducing the sharpness or the general geometry of the
      tip. Several devices which employ accelerated electrons to achieve this are
      described in the literature. To minimize both the effort to implement this
      technique in a UHV chamber and the overall duration of the cleaning procedure, we
      constructed a compact electron source fitted into a sample holder, which can be
      operated in a standard Omicron variable-temperature (VT)-STM while the tip stays
      in place. This way a maximum of compatibility with existing systems is achieved
      and short turnaround times are possible for tip cleaning.

PMID- 21895246
TI  - Systematic analyses of vibration noise of a vibration isolation system for high
      resolution scanning tunneling microscopes.
AB  - We designed and constructed an effective vibration isolation system for stable
      scanning tunneling microscopy measurements using a separate foundation and two
      vibration isolation stages (i.e., a combination of passive and active vibration
      isolation dampers). Systematic analyses of vibration data along the horizontal
      and vertical directions are present, including the vibration transfer functions
      of each stage and the overall vibration isolation system. To demonstrate the
      performance of the system, tunneling current noise measurements are conducted
      with and without the vibration isolation. Combining passive and active vibration
      isolation dampers successfully removes most of the vibration noise in the
      tunneling current up to 100 Hz. These comprehensive vibration noise data, along
      with details of the entire system, can be used to establish a clear guideline for
      building an effective vibration isolation system for various scanning probe
      microscopes and electron microscopes.

PMID- 21895247
TI  - Dynamic timber cell recognition using two-dimensional image measurement machine.
AB  - Image motion blur and defocus blur often occur when there is a relative motion
      between the imaging camera and the detected object. In this paper, we propose a
      robust timber cell recognition scheme using the low quality color timber cell
      images with the above-mentioned image blurs. First, a novel two-dimensional image
      measurement machine is devised, to obtain the object images sequentially by using
      a color camera. Second, the image-moment-based blur invariant features are
      calculated. Third, timber cell recognition is performed by using the computed
      Euclidean distance based on the moment invariants. We have experimentally proved
      that the effective use of image blur information improves the recognition
      accuracy of camera-captured timber cells. Moreover, the allowed maximum
      translation speed of the moving gallery is also discussed theoretically and
      experimentally. This scheme can identify the timber species by means of the cell
      recognition so as to judge the physical property and economic value of different
      timber species correctly.

PMID- 21895248
TI  - Angle dependence of the interaction distance in the shear force technique.
AB  - We study the interaction distance in the lateral force detection, using a
      standard quartz tuning fork as a force transducer. That is the distance at which
      the interaction sample-probe starts to be detected. We study in particular the
      dependence on the approaching angle. For angles smaller than 0.366 radians, we
      found an exponential behavior of the interaction distance as a function of the
      approaching angle. We show an equation that adjusts well with the experimental
      data, and discuss the possible phenomena.

PMID- 21895249
TI  - Cranz-Schardin camera with a large working distance for the observation of small
      scale high-speed flows.
AB  - The Cranz-Schardin camera utilizes a Q-switched Nd:YAG laser and four single CCD
      cameras. Light pulse energy in the range of 25 mJ and pulse duration of about 5
      ns is provided by the laser. The laser light is converted to incoherent light by
      Rhodamine-B fluorescence dye in a cuvette. The laser beam coherence is
      intentionally broken in order to avoid speckle. Four light fibers collect the
      fluorescence light and are used for illumination. Different light fiber lengths
      enable a delay of illumination between consecutive images. The chosen interframe
      time is 25 ns, corresponding to 40 * 10(6) frames per second. Exemplarily, the
      camera is applied to observe the bow shock in front of a water jet, propagating
      in air at supersonic speed. The initial phase of the formation of a jet structure
      is recorded.

PMID- 21895250
TI  - Scanning magneto-optical Kerr microscope with auto-balanced detection scheme.
AB  - We have developed a scanning magneto-optical Kerr microscope dedicated to
      localization and measurement of the in-plane magnetization of ultra-thin layered
      magnetic nanostructures with high sensitivity and signal-to-noise ratio. The
      novel light detection scheme is based on a differential photodetector with
      automatic common mode noise rejection system with a high noise suppression up to
      50 dB. The sensitivity of the developed detection scheme was tested by
      measurement of a single Co layer and a giant magnetoresistance (GMR) multilayer
      stack. The spatial resolution of the Kerr microscope was demonstrated by mapping
      an isolated 5*5 MUm spin-valve pillar.

PMID- 21895251
TI  - BioPhotonics workstation: a versatile setup for simultaneous optical
      manipulation, heat stress, and intracellular pH measurements of a live yeast
      cell.
AB  - In this study we have modified the BioPhotonics workstation (BWS), which allows
      for using long working distance objective for optical trapping, to include
      traditional epi-fluorescence microscopy, using the trapping objectives. We have
      also added temperature regulation of sample stage, allowing for fast temperature
      variations while trapping. Using this modified BWS setup, we investigated the
      internal pH (pH(i)) response and membrane integrity of an optically trapped
      Saccharomyces cerevisiae cell at 5 mW subject to increasing temperatures. The
      pH(i) of the cell is obtained from the emission of 5-(and-6)-carboxyfluorescein
      diacetate, succinimidyl ester, at 435 and 485 nm wavelengths, while the
      permeability is indicated by the fluorescence of propidium iodide. We present
      images mapping the pH(i) and permeability of the cell at different temperatures
      and with enough spatial resolution to localize these attributes within the cell.
      The combined capability of optical trapping, fluorescence microscopy and
      temperature regulation offers a versatile tool for biological research.

PMID- 21895252
TI  - Humidity response properties of a potentiometric sensor using LaF3 thin film as
      the solid electrolyte.
AB  - A thin-film type potentiometric sensor has been prepared by the implementation of
      electro-beam evaporation, rf magnetron sputtering methods, and micromachining
      processes. Sn film was deposited on n-Si/SiO(2) (400 nm) substrate. A deposited
      LaF(3) film was applied as solid electrolyte and sputtered Pt film was used as
      the sensing electrode. The patterns of the Pt and LaF(3) were realized by the
      micromachining processes. The LaF(3) film was characterized by scanning electron
      microscopy and energy dispersive x ray. Saturated aqueous solutions were used to
      achieve controlled humidity environments. When the sensor was exposed to humidity
      environments, the electromotive force (EMF) of the sensor was examined. It was
      found that the sensor varies with the relative humidity (RH). The stable response
      curve was presented and non-Nernst behavior between the average EMF values and RH
      may be shown.

PMID- 21895253
TI  - Rheo-small-angle neutron scattering at the National Institute of Standards and
      Technology Center for Neutron Research.
AB  - We describe the design and operation of a modified commercial rheometer to
      simultaneously perform rheological measurements and structural studies by small
      angle neutron scattering (SANS). The apparatus uses a Couette geometry shear cell
      allowing two of the three scattering planes to be observed by performing
      experiments in either the radial or tangential geometries. The device enables
      small angle neutron scattering patterns to be obtained simultaneously with a wide
      variety of rheological measurements such as stress/strain flow curves,
      oscillatory deformations, and creep, recovery and relaxation tests, from -20 
      degrees C to 150  degrees C, for samples with viscosities varying by several
      orders of magnitude. We give a brief report of recent experiments performed on a
      dispersion of acicular nanoparticles and biopolymer network under stress
      demonstrating the utility of such measurements. This device has been developed at
      the National Institute of Standards and Technology's Center for Neutron Research
      (NCNR) and made available to the complex fluids community as part of the standard
      sample environment equipment.

PMID- 21895254
TI  - A high temperature high pressure cell for quasielastic neutron scattering.
AB  - We present our recent development of a high temperature high pressure cell for
      neutron scattering. Combining a water cooled Nb1Zr pressure cell body with an
      internal heating furnace, the sample environment can reach temperatures of up to
      1500 K at a pressure of up to 200 MPa at the sample position, with an available
      sample volume of about 700 mm(3). The cell material Nb1Zr is specifically chosen
      due to its reasonable mechanical strength at elevated temperatures and fairly
      small neutron absorption and incoherent scattering cross sections. With this
      design, an acceptable signal-to-noise ratio of about 10:1 can be achieved. This
      opens new possibilities for quasielastic neutron scattering studies on different
      types of neutron spectrometers under high temperature high pressure conditions,
      which is particularly interesting for geological research on, e.g., water
      dynamics in silicate melts.

PMID- 21895255
TI  - Laboratory test reactor for the investigation of liquid reducing agents in the
      selective catalytic reduction of NOx.
AB  - A test reactor was designed and built for investigating liquid reducing agents in
      the selective catalytic reduction (SCR) process in the laboratory. The design of
      the experimental setup is described in detail and its performance was evaluated.
      Using a glass nebulizer, liquid reducing agents were sprayed directly onto a
      catalyst positioned in a heated glass reactor with a length of 250 mm and an
      internal diameter of 20.4 mm or 40 mm. Model exhaust gases were mixed from
      individual gas components and were heated up to 450  degrees C in a heat
      exchanger before entering the reactor. The off-gas was analyzed using two
      complimentary techniques, a multi-component online FTIR gas analysis and a liquid
      quench gas absorption setup, to detect higher molecular compounds and aerosols.
      Due to the versatility of construction, processes not related to SCR, but
      involving three-phase reactions with gases, liquids and a catalyst, can also be
      investigated.

PMID- 21895256
TI  - High-temperature and high-pressure pulsed synthesis apparatus for supercritical
      production of nanoparticles.
AB  - In materials science continuous flow supercritical fluid reactors are widely used
      for highly controlled synthesis of nanoparticles. The major limitation of
      continuous flow reactors is that the inherent distribution of residence times
      leads to broadening of the corresponding size distribution of the nanoparticles,
      and in addition it is not possible to carry out synthesis with very short or very
      long reaction times. Here, we report a new synthesis concept that we call pulsed
      synthesis, which removes the limitations of flow synthesis at the expense of a
      more complex reactor design and extensive computer control. Another limitation of
      flow synthesis is that it is largely a black box, where limited direct
      information is available of the specific chemical reactions taking place, the
      particle nucleation, the particle growth, etc. Such information is commonly
      obtained from in situ synchrotron and neutron scattering studies, but transfer of
      information from in situ studies with static reactors to laboratory flow reactor
      conditions is highly non-trivial. The new pulse reactor provides superior heating
      rates, arbitrary residence times with narrow distribution limited only by the
      pulse duration, and the ability of using the same reactor both for nanoparticle
      production and in situ synchrotron studies; thus eliminating the need for
      transfer of in situ information to laboratory reactor designs.

PMID- 21895257
TI  - A shock tube with a high-repetition-rate time-of-flight mass spectrometer for
      investigations of complex reaction systems.
AB  - A conventional membrane-type stainless steel shock tube has been coupled to a
      high-repetition-rate time-of-flight mass spectrometer (HRR-TOF-MS) to be used to
      study complex reaction systems such as the formation of pollutants in combustion
      processes or formation of nanoparticles from metal containing organic compounds.
      Opposed to other TOF-MS shock tubes, our instrument is equipped with a modular
      sampling unit that allows to sample with or without a skimmer. The skimmer unit
      can be mounted or removed in less than 10 min. Thus, it is possible to adjust the
      sampling procedure, namely, the mass flux into the ionization chamber of the HRR
      TOF-MS, to the experimental situation imposed by species-specific ionization
      cross sections and vapor pressures. The whole sampling section was optimized with
      respect to a minimal distance between the nozzle tip inside the shock tube and
      the ion source inside the TOF-MS. The design of the apparatus is presented and
      the influence of the skimmer on the measured spectra is demonstrated by comparing
      data from both operation modes for conditions typical for chemical kinetics
      experiments. The well-studied thermal decomposition of acetylene has been used as
      a test system to validate the new setup against kinetics mechanisms reported in
      literature.

PMID- 21895258
TI  - Infrared multiphoton dissociation tandem charge detection-mass spectrometry of
      single megadalton electrosprayed ions.
AB  - This work presents the implementation of tandem mass spectrometry for experiments
      on single electrosprayed ions from compounds of megadalton (MDa) molecular
      weight, using two charge detection devices. The first mass spectrometry stage
      (first charge detection device) combined with an ion gate allows both mass-to
      charge ratio and charge selections of the megadalton ion of interest. The second
      stage is based on an electrostatic ion trap and consists of an image charge
      detection tube mounted between two ion mirrors. Single MDa ions can be stored for
      several dozen milliseconds. During the trapping time, single ions can be
      irradiated by a continuous wavelength CO(2) laser. We observe stepwise changes in
      the charge of a single trapped ion owing to multiphoton activation. Illustration
      of infrared multiphoton dissociation tandem mass spectrometry are given for
      single megadalton ions of poly(ethylene oxide)s and DNAs.

PMID- 21895259
TI  - Non-invasive and high-sensitivity scanning detection of magnetic nanoparticles in
      animals using high-Tc scanning superconducting-quantum-interference-device
      biosusceptometry.
AB  - Although magnetic nanoparticles (MNPs) have been widely applied to animals in
      biomedicine, MNPs within animals should be examined in real time, in vivo, and
      without bio-damaged possibility to evaluate whether the bio-function of MNPs is
      valid or to further controls the biomedicinal process because of accompanying
      complex problems such as MNPs distribution and MNPs biodegradation. The non
      invasive and high-sensitivity scanning detection of MNPs in animals using ac
      susceptometry based on a high-T(c) superconducting quantum interference device
      (SQUID) is presented. The non-invasive results and biopsy results show good
      agreement, and two gold-standard biomedicine methods, Prussian blue stain and
      inductively coupled plasma, prove the magnetic results. This confirms that the
      future clinical diagnosis of bio-functional MNPs could be operated by using
      scanning SQUID biosusceptometry as conveniently as an ultrasonic probe.

PMID- 21895260
TI  - Temperature dependence dynamical permeability characterization of magnetic thin
      film using near-field microwave microscopy.
AB  - A temperature dependence characterization system of microwave permeability of
      magnetic thin film up to 5 GHz in the temperature range from room temperature up
      to 423 K is designed and fabricated as a prototype measurement fixture. It is
      based on the near field microwave microscopy technique (NFMM). The scaling
      coefficient of the fixture can be determined by (i) calibrating the NFMM with a
      standard sample whose permeability is known; (ii) by calibrating the NFMM with an
      established dynamic permeability measurement technique such as shorted microstrip
      transmission line perturbation method; (iii) adjusting the real part of the
      complex permeability at low frequency to fit the value of initial permeability.
      The algorithms for calculating the complex permeability of magnetic thin films
      are analyzed. A 100 nm thick FeTaN thin film deposited on Si substrate by
      sputtering method is characterized using the fixture. The room temperature
      permeability results of the FeTaN film agree well with results obtained from the
      established short-circuited microstrip perturbation method. Temperature
      dependence permeability results fit well with the Landau-Lifshitz-Gilbert
      equation. The temperature dependence of the static magnetic anisotropy H(K)(sta),
      the dynamic magnetic anisotropy H(K)(dyn), the rotational anisotropy H(rot),
      together with the effective damping coefficient alpha(eff), ferromagnetic
      resonance f(FMR), and frequency linewidth Deltaf of the thin film are
      investigated. These temperature dependent magnetic properties of the magnetic
      thin film are important to the high frequency applications of magnetic devices at
      high temperatures.

PMID- 21895261
TI  - Digitally gain controlled linear high voltage amplifier for laboratory
      applications.
AB  - The design of a digitally gain controlled high-voltage non-inverting bipolar
      linear amplifier is presented. This cost efficient and relatively simple circuit
      has stable operation range from dc to 90 kHz under the load of 10 kOmega and 39
      pF. The amplifier can swing up to 360 V(pp) under these conditions and it has 2.5
      MUs rise time. The gain can be changed by the aid of JFETs. The amplifiers have
      been realized using a combination of operational amplifiers and high-voltage
      discrete bipolar junction transistors. The circuit details and performance
      characteristics are discussed.

PMID- 21895262
TI  - Design and performance of a pulse transformer based on Fe-based nanocrystalline
      core.
AB  - A dry-type pulse transformer based on Fe-based nanocrystalline core with a load
      of 0.88 nF, output voltage of more than 65 kV, and winding ratio of 46 is
      designed and constructed. The dynamic characteristics of Fe-based nanocrystalline
      core under the impulse with the pulse width of several microseconds were studied.
      The pulse width and incremental flux density have an important effect on the
      pulse permeability, so the pulse permeability is measured under a certain pulse
      width and incremental flux density. The minimal volume of the toroidal pulse
      transformer core is determined by the coupling coefficient, the capacitors of the
      resonant charging circuit, incremental flux density, and pulse permeability. The
      factors of the charging time, ratio, and energy transmission efficiency in the
      resonant charging circuit based on magnetic core-type pulse transformer are
      analyzed. Experimental results of the pulse transformer are in good agreement
      with the theoretical calculation. When the primary capacitor is 3.17 MUF and
      charge voltage is 1.8 kV, a voltage across the secondary capacitor of 0.88 nF
      with peak value of 68.5 kV, rise time (10%-90%) of 1.80 MUs is obtained.

PMID- 21895263
TI  - A repetitive S-band long-pulse relativistic backward-wave oscillator.
AB  - This paper presents both numerical and experimental studies of a repetitive S
      band long-pulse relativistic backward-wave oscillator. The dispersion relation
      curve of the main slow-wave structure is given by the numerical calculation.
      Experimental results show that a 1 GW microwaves with pulse duration of about 100
      ns (full width of half magnitude) under 10 Hz repetitive operation mode are
      obtained. The microwave frequency is 3.6 GHz with the dominant mode of TM(01),
      and power conversion efficiency is about 20%. The single pulse energy is about
      100 J. The experimental results are in good agreement with the simulation ones.
      By analyzing the experimental phenomenon, we obtain the conclusion that the
      explosive emission on the surface of the electrodynamics structure in intense
      radio frequency field mainly leads to the earlier unexpected termination of
      microwave output.

PMID- 21895264
TI  - High voltage pulse shaping of e-beam diode using perveance variation.
AB  - This paper presents a new high voltage pulse shaping methodology for pulsed power
      applications. The aim is to generate high voltage square pulse across anode
      cathode gap of e-beam diodes. The non-linear time varying perveance
      characteristics of e-beam diodes are used for shaping of output voltage pulse
      across it, generated directly from Marx generator. Analytically, it has been
      shown in the paper that under certain conditions, if achieved, Marx generator
      feeding an e-beam diode can produce a square-like pulse at the output, without
      any extra pulse shaping arrangements. Experimental results to support the
      analysis are also presented in the paper.

PMID- 21895265
TI  - Optical temperature sensor based on ZnO thin film's temperature-dependent optical
      properties.
AB  - A reflective fiber temperature sensor system based on the ZnO thin film is
      proposed. The transmittance spectra and temperature dependent optical property of
      the sensing head with ZnO thin film is investigated theoretically and
      experimentally, and the temperature resolution of ~1  degrees C is obtained in
      the temperature region of 300-773 K. The temperature sensing system is only
      related to the wavelength shift of transmittance spectra, and has a high
      stability without depending on the incident light intensity. This research
      results also indicate a fiber optical sensor with a broad temperature measurement
      range (10-1800 K) can be gained as a promising temperature sensing device, and
      can be applied into some extremely environments, such as aircraft, nuclear power
      station and power transmission system, and so on.

PMID- 21895266
TI  - Characteristics and measurement of supersonic projectile shock waves by a 32
      microphone ring array.
AB  - This paper discusses about the characteristics of supersonic projectile shock
      wave in muzzle region during firing of high explosive anti-tank (HEAT) and high
      explosive (HE) projectiles. HEAT projectiles are fired horizontally at a muzzle
      velocity of Mach 3.5 from a medium caliber tank gun equipped with a newly
      designed multi-perforated muzzle brake, whereas HE projectiles are fired at
      elevation angles at a muzzle velocity of Mach 2 from a large caliber howitzer
      equipped with a newly designed double-baffle muzzle brake. In the near field,
      pressure signatures of the N-wave generated from projectiles are measured by 32
      microphone ring array wrapped by cotton sheath. Records measured by the
      microphone array are used to demonstrate several key characteristics of the shock
      wave of supersonic projectile. All measurements made in this study can be a
      significant reference for developing guns, tanks, or the chassis of fighting
      vehicles.

PMID- 21895267
TI  - New photoacoustic cell design for studying aqueous solutions and gels.
AB  - A new photoacoustic (PA) cell design, which is particularly suitable for
      investigations of liquids, gels, and outgassing samples is presented. The setup
      is based on a PA cell of only 78.5 mm(3) volume, which is sealed on the sample
      side with either a 163 MUm thick chemical vapor deposition diamond window or a
      3.91 MUm thin diamond membrane. This design offers great advantages compared to
      traditionally used open-ended PA cells especially when investigating volatile
      compounds. The new PA cell design is particularly interesting in the studies of
      biological samples characterized by a high water content. The performance was
      demonstrated with mid-infrared PA measurements of glucose in aqueous solutions
      using a tunable quantum-cascade laser as a light source. A detection limit of 100
      mg/dl (SNR = 3) has been achieved. Furthermore, the spectral changes of glucose
      dissolved in water caused by mutorotation have been monitored time-resolved.

PMID- 21895268
TI  - Dynamic junction temperature measurement for high power light emitting diodes.
AB  - Junction temperature of high power light emitting diodes (LEDs), which is crucial
      for the thermal management of solid-state lighting, needs to be measured
      accurately. In this paper, a dynamic junction temperature measurement system for
      LEDs was proposed and the calibration including instrument calibration and factor
      K calibration were presented. The influence of the fast switch time in dynamic
      junction temperature test was analyzed and measurement errors caused by sampling
      delay were quantified. To prove the accuracy of the present system, comparison
      experiment was conducted. It shows a good agreement between the experimental data
      and reference value. Experiments also show that the measurement accuracy of the
      instrument can be up to 0.1  degrees C, and the standard error of temperature
      measurement can be controlled within 1%.

PMID- 21895269
TI  - Quantitative calcium resistivity based method for accurate and scalable water
      vapor transmission rate measurement.
AB  - The development of flexible organic light emitting diode displays and flexible
      thin film photovoltaic devices is dependent on the use of flexible, low-cost,
      optically transparent and durable barriers to moisture and/or oxygen. It is
      estimated that this will require high moisture barriers with water vapor
      transmission rates (WVTR) between 10(-4) and 10(-6) g/m(2)/day. Thus there is a
      need to develop a relatively fast, low-cost, and quantitative method to evaluate
      such low permeation rates. Here, we demonstrate a method where the resistance
      changes of patterned Ca films, upon reaction with moisture, enable one to
      calculate a WVTR between 10 and 10(-6) g/m(2)/day or better. Samples are
      configured with variable aperture size such that the sensitivity and/or
      measurement time of the experiment can be controlled. The samples are connected
      to a data acquisition system by means of individual signal cables permitting
      samples to be tested under a variety of conditions in multiple environmental
      chambers. An edge card connector is used to connect samples to the measurement
      wires enabling easy switching of samples in and out of test. This measurement
      method can be conducted with as little as 1 h of labor time per sample.
      Furthermore, multiple samples can be measured in parallel, making this an
      inexpensive and high volume method for measuring high moisture barriers.

PMID- 21895270
TI  - Self-integrating inductive loop for measuring high frequency pulses.
AB  - High frequency pulses can be measured by means of inductive sensors. The main
      advantage of these sensors consists of non-contact measurements that isolate and
      protect measuring equipment. The objective of this paper is to present the
      implementation of an inductive sensor for measuring rapidly varying currents. It
      consists of a rectangular loop with a resistor at its terminals. The inductive
      loop gives the derivative of the current according to Faraday's law and the
      resistor connected to the loop modifies the sensor's frequency response to obtain
      an output proportional to the current pulse. The self-integrating inductive
      sensor was validated with two sensors, a non-inductive resistor and a commercial
      high frequency current transformer. The results were compared to determine the
      advantages and drawbacks of the probe as an adequate inductive transducer.

PMID- 21895271
TI  - A range-based method to calibrate a magnetic spectrometer measuring the energy
      spectrum of the backward electron beam of a plasma focus.
AB  - The electron beam emitted from the back of plasma focus devices is being studied
      as a radiation source for intraoperative radiation therapy applications. A plasma
      focus device is being developed for this purpose, and there is a need for
      characterizing its electron beam, particularly, insofar as the energy spectrum is
      concerned. The instrument used is a magnetic spectrometer. To calibrate this
      spectrometer, a procedure relying on the energy-range relation in Mylar(r) has
      been devised and applied. By measuring the transmission through increasing
      thicknesses of the material, electron energies could be assessed and compared to
      the spectrometer readings. Thus, the original calibration of the instrument has
      been extended to higher energies and also to better accuracy. Methods and results
      are presented.

PMID- 21895272
TI  - High-speed analog fiber-optic link for electromagnetic interference suppression
      in infrared power measurement.
AB  - Electromagnetic interference (EMI) is a common problem in a high-power pulsed
      infrared laser measurement. In order to eliminate susceptibility to radiated EMI,
      we developed, tested and implemented an infrared power measurement system using a
      high-speed analog fiber-optic link. Key components are commercially available
      parts designed for high-speed digital data transmission, but can be operated in
      analog mode. We successfully utilized the system for time-resolved measurements
      of high-power transversely-excited atmospheric-pressure CO(2) lasers in amplifier
      and oscillator configurations. This paper presents experimental setup, testing
      results, and the details of the laser power measurements results.

PMID- 21895273
TI  - A novel smooth impact drive mechanism actuation method with dual-slider for a
      compact zoom lens system.
AB  - In this paper, a novel actuation method for a smooth impact drive mechanism that
      positions dual-slider by a single piezo-element is introduced and applied to a
      compact zoom lens system. A mode chart that determines the state of the slider at
      the expansion or shrinkage periods of the piezo-element is presented, and the
      design guide of a driving input profile is proposed. The motion of dual-slider
      holding lenses is analyzed at each mode, and proper modes for zoom functions are
      selected for the purpose of positioning two lenses. Because the proposed
      actuation method allows independent movement of two lenses by a single piezo
      element, the zoom lens system can be designed to be compact. For a feasibility
      test, a lens system composed of an afocal zoom system and a focusing lens was
      developed, and the passive auto-focus method was implemented.

PMID- 21895274
TI  - One hundred anode microchannel plate ion detector.
AB  - A one-hundred-anode microchannel plate detector is constructed on a 10 cm * 15 cm
      printed circuit board and attached to a homebuilt matrix assisted laser
      desorption ionization (MALDI) time-of-flight mass spectrometer. Ringing and cross
      talk between anodes have been successfully eliminated and preliminary mass
      spectra of peptide ions recorded. With one hundred anodes on the printed circuit
      board, spatial information about the ion beam can also be readily determined with
      this detector. During operation, the detector anode assembly loses sensitivity
      after ions strike it for a considerable period of time due to charging of the non
      conductive regions between anodes. However, this effect can be minimized by
      deflecting matrix ions away from the detector.

PMID- 21895275
TI  - Experimental study of a semi-passive ventilation grille with a feedback control
      system.
AB  - The diffusion of window frames with low air permeability, due to the energy
      saving regulations, has implied in several cases the worsening of the indoor
      microclimate and air quality. On the other hand, air-tight window frames imply
      uncontrolled and too high air change rates. The mechanical ventilation not always
      is a practicable solution because of economic reasons and because it implies
      energy waste. Various Italian and European environmental and energetic laws take
      into consideration and promote the use of controlled natural ventilation, though
      this definition is not associated to well defined and tested technical solutions.
      An adequate solution can be achieved by using semi-passive self adjustable
      ventilation devices, able to ensure controlled changes of indoor air. In this
      paper, a semi-passive damper with a feedback control system is proposed and its
      behavior is investigated by means of experimental study. The presented semi
      passive grille allows to control the air flow rate, injected into the room by
      natural or artificial pressure gradient, more effectively than the usual passive
      ventilation grilles made available by the present industrial production. However,
      since the semi-passive grille has a one-way flow, in the natural ventilation of a
      flat the proper functioning of the system could be ensured with a more complex
      configuration, with respect to the passive self-regulating grilles, able to limit
      the flow of fresh air in the presence of high levels of Deltap; conversely, it
      could have widespread use in applications requiring a more accurate control of
      airflow in case of mechanical ventilation plants.

PMID- 21895276
TI  - The new cold neutron chopper spectrometer at the Spallation Neutron Source:
      design and performance.
AB  - The design and performance of the new cold neutron chopper spectrometer (CNCS) at
      the Spallation Neutron Source in Oak Ridge are described. CNCS is a direct
      geometry inelastic time-of-flight spectrometer, designed essentially to cover the
      same energy and momentum transfer ranges as IN5 at ILL, LET at ISIS, DCS at NIST,
      TOFTOF at FRM-II, AMATERAS at J-PARC, PHAROS at LANSCE, and NEAT at HZB, at
      similar energy resolution. Measured values of key figures such as neutron flux at
      sample position and energy resolution are compared between measurements and ray
      tracing Monte Carlo simulations, and good agreement (better than 20% of absolute
      numbers) has been achieved. The instrument performs very well in the cold and
      thermal neutron energy ranges, and promises to become a workhorse for the neutron
      scattering community for quasielastic and inelastic scattering experiments.

PMID- 21895277
TI  - A time-of-flight backscattering spectrometer at the Spallation Neutron Source,
      BASIS.
AB  - We describe the design and current performance of the backscattering silicon
      spectrometer (BASIS), a time-of-flight backscattering spectrometer built at the
      spallation neutron source (SNS) of the Oak Ridge National Laboratory (ORNL).
      BASIS is the first silicon-based backscattering spectrometer installed at a
      spallation neutron source. In addition to high intensity, it offers a high-energy
      resolution of about 3.5 MUeV and a large and variable energy transfer range.
      These ensure an excellent overlap with the dynamic ranges accessible at other
      inelastic spectrometers at the SNS.

PMID- 21895278
TI  - Thermoelectric temperature control device for vapor pressure measurements.
AB  - The static method of measuring equilibrium vapor pressure requires locating the
      sample at the coldest part of the apparatus to avoid errors due to evaporation
      and recondensation elsewhere. This paper describes a device that can hold the
      sample 1 K below the temperature of the surrounding air without a liquid bath. It
      comprises a pair of thermoelectric elements and two thermometers attached to an
      insulated aluminum block. The device can operate as high as 200  degrees C while
      controlling the sample with a precision of 0.02 K; below 110  degrees C, the
      precision is 2 mK. Also described is a method to measure the small temperature
      offset due to heat flow between the sample and the surrounding aluminum block.
      The uncertainty due to the offset is small compared to the 6 mK uncertainty due
      to the thermometer.

PMID- 21895279
TI  - Note: Vector reflectometry in a beam waveguide.
AB  - We present a one-port calibration technique for characterization of beam
      waveguide components with a vector network analyzer. This technique involves
      using a set of known delays to separate the responses of the instrument and the
      device under test. We demonstrate this technique by measuring the reflected
      performance of a millimeter-wave variable-delay polarization modulator.

PMID- 21895280
TI  - Note: Direct force and ionic-current measurements on DNA in a nanocapillary.
AB  - We have developed optical tweezers, with force measurements based on fast video
      tracking, for analysis and control of DNA translocation through nanocapillaries.
      Nanocapillaries are single-molecule biosensors with very similar characteristics
      to solid-state nanopores. Our novel experimental setup allows for ionic-current
      measurements in which the nanocapillary is oriented perpendicular to the trapping
      laser. Using video-based particle tracking, we are able to measure the position
      of DNA coated colloids at sub-millisecond resolution and in real-time. We present
      the first electrophoretic force and simultaneous ionic-current measurements of a
      single DNA molecule inside the orifice of a nanocapillary.

PMID- 21895281
TI  - Note: Design and construction of a simple and reliable printed circuit board
      substrate Bradbury-Nielsen gate for ion mobility spectrometry.
AB  - A less laborious, structure-simple, and performance-reliable printed circuit
      board (PCB) based Bradbury-Nielsen gate for high-resolution ion mobility
      spectrometry was introduced and investigated. The gate substrate was manufactured
      using a PCB etching process with small holes (Phi 0.1 mm) drilled along the gold
      plated copper lines. Two interdigitated sets of rigid stainless steel spring wire
      (Phi 0.1 mm) that stands high temperature and guarantees performance stability
      were threaded through the holes. Our homebuilt ion mobility spectrometer mounted
      with the gate gave results of about 40 for resolution while keeping a signal
      intensity of over 0.5 nano-amperes.

PMID- 21895282
TI  - Note: Seesaw actuation of atomic force microscope probes for improved imaging
      bandwidth and displacement range.
AB  - The authors describe a method of actuation for atomic force microscope (AFM)
      probes to improve imaging speed and displacement range simultaneously. Unlike
      conventional piezoelectric tube actuation, the proposed method involves a lever
      and fulcrum "seesaw" like actuation mechanism that uses a small, fast
      piezoelectric transducer. The lever arm of the seesaw mechanism increases the
      apparent displacement range by an adjustable gain factor, overcoming the standard
      tradeoff between imaging speed and displacement range. Experimental
      characterization of a cantilever holder implementing the method is provided
      together with comparative line scans obtained with contact mode imaging. An
      imaging bandwidth of 30 kHz in air with the current setup was demonstrated.

PMID- 21895283
TI  - Note: Multi-point measurement of |B| in the gas-dynamic trap with a spectral
      motional Stark effect diagnostic.
AB  - An upgraded spectral motional Stark effect diagnostic has been installed on the
      gas-dynamic trap (GDT) experiment to enable spatially resolved measurement of
      |B|. A new low-noise charge-coupled device detector, combined with enhancements
      of the diagnostic neutral beam, allows single-shot profile measurements.
      Previously only single-point motional Stark effect measurements were possible,
      and detector noise severely limited measurement precision, requiring multi-shot
      averaging. The plasma pressure profile in GDT is derived from the measured
      diamagnetic modification of |B| and used to examine the conditions of stable
      plasma confinement at high plasma pressure.

PMID- 21895284
TI  - Note: Demonstration of an external-cavity diode laser system immune to current
      and temperature fluctuations.
AB  - We demonstrate an external-cavity laser system using an anti-reflection coated
      laser diode as gain medium with about 60 nm fluorescence spectrum, and a Rb
      Faraday anomalous dispersion optical filter (FADOF) as frequency-selecting
      element with a transmission bandwidth of 1.3 GHz. With 6.4% optical feedback, a
      single stable longitudinal mode is obtained with a linewidth of 69 kHz. The
      wavelength of this laser is operating within the center of the highest
      transmission peak of FADOF over a diode current range from 55 mA to 142 mA and a
      diode temperature range from 15  degrees C to 35  degrees C, thus it is immune to
      the fluctuations of current and temperature.

PMID- 21895285
TI  - Note: Miniature 120-kV autonomous generator based on transverse shock-wave
      depolarization of Pb(Zr0.52Ti0.48)O3 ferroelectrics.
AB  - The design of autonomous ultrahigh-voltage generators with no moving metallic
      parts based on transverse explosive shock wave depolarization of
      Pb(Zr(0.52)Ti(0.48))O(3) (PZT 52/48) poled ferroelectrics was explored and
      studied. It follows from experimental results that the output voltage produced by
      the shock-wave ferroelectric generators (FEGs) is directly proportional to the
      number of PZT 52/48 elements connected in series. It was demonstrated that
      miniature FEGs (volume less than 180 cm(3)) were capable of reliably producing
      output voltage pulses with amplitudes exceeding 120 kV which is the record
      reported in open literature.

PMID- 21895286
TI  - Note: Measurement method for sound velocity of melts in large volume press and
      its application to liquid sodium up to 2.0 GPa.
AB  - Based on large volume press and conventional pulse-echo ultrasonic technique, we
      have overcome the difficulty in determining the length of liquid specimen under
      high pressure, and the sound velocity in liquid Na has been measured up to 2 GPa.
      The P-V data deduced by our sound velocity results through equation of state is
      in an excellent agreement with previous data directly determined by piezometer
      method. This new experimental technique is convenient and ready for use, being
      expected to advance investigation on thermodynamic properties of liquid metals
      and other melts under high pressure.

PMID- 21895287
TI  - Note: Determination of temperature dependence of GaP bandgap energy from diode
      temperature response characteristics.
AB  - A simple method of E(g)(T) dependence determination for active areas of
      semiconductor devices based on wide bandgap semiconductors has been proposed and
      developed. Verification of the method has been carried out while determining
      E(g)(T) dependence in a base area of p(+)-n-type GaP diodes in the temperature
      range 77-523 K. The method is based on U-T characterization of the diodes and
      calculation of E(g)(T) dependence according to the expression obtained within
      present study. Satisfactory agreement between experimental and theoretical
      results has been achieved including references available on gallium phosphide.
      The method proposed could be applied to experimental data processing in high
      temperature thermometry.

PMID- 21895288
TI  - Note: Non-destructive measurement of thermal effusivity of a solid and liquid
      using a freestanding serpentine sensor-based 3omega technique.
AB  - A non-destructive thermal effusivity characterization method described as a
      freestanding serpentine sensor-based 3omega technique was reported. This
      freestanding serpentine sensor was fabricated by the mature flexible printed
      circuit production technique. Expression for the temperature response of the
      freestanding serpentine sensor with respect to the thermal effusivity of the test
      sample was presented. The technique was further verified by measuring four kinds
      of standard samples at room temperature. Experimental results which well agree
      with reference values demonstrate the new technique is of great application value
      to thermal effusivity characterization of solids, liquids, and structures to
      which the conventional 3omega technique is not applicable, e.g., solids with
      porous surfaces.

PMID- 21895289
TI  - Note: High speed optical profiler based on a phase-shifting technique using
      frequency-scanning lasers.
AB  - We present a high speed optical profiler (HSOP) using frequency-scanning lasers
      for three-dimensional profile measurements of microscopic structures. To improve
      upon previous techniques for implementing the HSOP, we developed frequency
      scanning lasers and a compact microscopic interferometer. The controller of the
      HSOP was also modified to generate proper phase-shifting steps. For measurements
      of step height specimens, the HSOP showed results comparable with a commercial
      optical profiler, even with much higher measurement speeds (up to 30 Hz). The
      typical repeatability of step height measurement was less than 1 nm. We also
      present measurements of microscopic structures to verify the HSOP's ability to
      perform high speed inline inspection for the semiconductor and flat-panel display
      industries.

PMID- 21895290
TI  - Note: Detection of a single cobalt microparticle with a microfabricated atomic
      magnetometer.
AB  - We present magnetic detection of a single, 2 MUm diameter cobalt microparticle
      using an atomic magnetometer based on a microfabricated vapor cell. These results
      represent an improvement by a factor of 10(5) in terms of the detected magnetic
      moment over previous work using atomic magnetometers to detect magnetic
      microparticles. The improved sensitivity is due largely to the use of small vapor
      cells. In an optimized setup, we predict detection limits of 0.17 MUm(3).

PMID- 21895291
TI  - Note: Piezoelectric strain voltage sensing at ultra-low frequencies.
AB  - Piezoelectric sensors have emerged as a versatile tool for measurement of various
      quantities such as pressure, acceleration, strain, or force across many
      industrial applications. When mechanically strained, electric charges are
      produced inside a piezoelectric transducer. These charges result in an electric
      field that may be measured as a voltage difference between two electrodes, from
      which the strain can be inferred. To measure this voltage the sensor must be
      interfaced with an external device that would typically have a finite input
      impedance. This, together with the capacitive nature of the piezoelectric sensor,
      results in an inability to measure strain at low frequencies. We propose a
      method, based on using a varactor diode in an oscillator circuit, which can
      result in accurate measurements of the piezoelectric voltage at ultra-low
      frequencies. We demonstrate successful measurements at 1 mHz.

PMID- 21895292
TI  - Note: Vector network analyzer-ferromagnetic resonance spectrometer using high Q
      factor cavity.
AB  - A ferromagnetic resonance (FMR) spectrometer whose main components consist of an
      X-band resonator and a vector network analyzer (VNA) was developed. This
      spectrometer takes advantage of a high Q-factor (9600) cavity and state-of-the
      art VNA. Accordingly, field modulation lock-in technique for signal to noise
      ratio (SNR) enhancement is no longer necessary, and FMR absorption can therefore
      be extracted directly. Its derivative for the ascertainment of full width at half
      maximum height of FMR peak can be found by taking the differentiation of original
      data. This system was characterized with different thicknesses of permalloy (Py)
      films and its multilayer, and found that the SNR of 5 nm Py on glass was better
      than 50, and did not have significant reduction even at low microwave excitation
      power (-20 dBm), and at low Q-factor (3000). The FMR other than X-band can also
      be examined in the same manner by using a suitable band cavity within the
      frequency range of VNA.

PMID- 21895293
TI  - Note: Fabrication of tapered fibre tip using mechanical polishing method.
AB  - Tapered fibre tips fabricated using mechanical polishing method is studied. The
      fibre tips are formed by sequential polishing flat-ended single mode fibres with
      decreasing aluminium oxide polishing film grit size. Based on the proposed
      technique, tapered fibre tips with cone angle ranging from 30 degrees  to 130
      degrees  are fabricated by controlling the polishing angle. Besides the variety
      of cone angle, considerable smoothness of the fibre tip surface may assist in
      good metal coating and hence a well-defined aperture can be obtained. In
      addition, this paper presents a two-step hybrid fabrication method combining the
      proposed polishing method with chemical etching method to increase the possible
      fibre tip cone angles achievable by chemical etching method.

PMID- 21895294
TI  - Note: Continuous synthesis of uniform vertical graphene on cylindrical surfaces.
AB  - This note describes a new reactor design for continuous synthesis of vertically
      oriented graphene (VG) sheets on cylindrical wire substrates using an atmospheric
      plasma-enhanced chemical vapor deposition (PECVD) system. Through combining a U
      shaped reactor design with "dynamic mode" synthesis featuring simultaneous
      rotational and axial movements of the metallic wire substrate, the new setup can
      enable continuous synthesis of VG sheets on the wire surface with remarkable
      uniformity in both circumferential and axial directions. In contrast, synthesis
      of VG at "static mode" with a fixed substrate can only lead to non-uniform growth
      of VG sheets on the wire surface. Potential applications of the resulting uniform
      VG-coated metallic wire could include field emitters, field-ionization-based
      neutral atom detectors, and indoor corona discharges.

PMID- 21895295
TI  - Note: Two-dimensional resistivity mapping method for characterization of thin
      films and nanomaterials.
AB  - A two-dimensional resistivity mapping method is presented as an analysis tool for
      thin films. The spatial distribution of resistivity in the interior of the film
      is reconstructed with the data measured on its periphery. A square window with
      four electrodes on each side is fabricated as the test vehicle. While the current
      is applied to one electrode, the potentials on the other electrodes are monitored
      and an iterative method generates the resistivity map. The technique is
      demonstrated by measurements on a homogeneous organic PEDOT:PSS film and an
      inhomogeneous ZnO nanoparticle coating.

PMID- 21895301
TI  - Comparative study of the angle-resolved backscattering properties of collagen
      fibers in bovine tendon and cartilage.
AB  - In a biological tissue, light scattering is based on the size and type of
      scatterers seen as refractive index variations that describe the optical
      properties shown. In this paper, we have implemented the variable incidence angle
      technique of multiple angle of illumination experiment on tendon and cartilage
      samples whose dominant constituents are genetically different types of collagen
      fibers, type I and type II, respectively. It is found that tendon displays a much
      greater angular anisotropy in its optical backscattering coefficient than the
      healthy cartilage. We propose that this is due to a more uniform distribution of
      fine fibrils than is found in tendon. Rayleigh-Gans approximation is used to give
      qualitative support to this idea.

PMID- 21895302
TI  - Coregistered photoacoustic-ultrasound imaging applied to brachytherapy.
AB  - Brachytherapy is a form of radiation therapy commonly used in the treatment of
      prostate cancer wherein sustained radiation doses can be precisely targeted to
      the tumor area by the implantation of small radioactive seeds around the
      treatment area. Ultrasound is a popular imaging mode for seed implantation, but
      the seeds are difficult to distinguish from the tissue structure. In this work,
      we demonstrate the feasibility of photoacoustic imaging for identifying
      brachytherapy seeds in a tissue phantom, comparing the received intensity to
      endogenous contrast. We have found that photoacoustic imaging at 1064 nm can
      identify brachytherapy seeds uniquely at laser penetration depths of 5 cm in
      biological tissue at the ANSI limit for human exposure with a contrast-to-noise
      ratio of 26.5 dB. Our realtime combined photoacoustic-ultrasound imaging approach
      may be suitable for brachytherapy seed placement and post-placement verification,
      potentially allowing for realtime dosimetry assessment during implantation.

PMID- 21895303
TI  - Photoacoustic microscopy of tyrosinase reporter gene in vivo.
AB  - Photoacoustic tomography is a hybrid modality based on optical absorption
      excitation and ultrasonic detection. It is sensitive to melanin, one of the
      primary absorbers in skin. For cells that do not naturally contain melanin,
      melanin production can be induced by introducing the gene for tyrosinase, the
      primary enzyme responsible for expression of melanin in melanogenic cells.
      Optical resolution photoacoustic microscopy was used in the ex vivo study
      reported here, where the signal from transfected cells increased by more than 10
      times over wild-type cells. A subsequent in vivo experiment was conducted to
      demonstrate the capability of photoacoustic microscopy to spectrally
      differentiate between tyrosinase-catalyzed melanin and various other absorbers in
      tissue.

PMID- 21895304
TI  - Simultaneous in vivo imaging of melanin and lipofuscin in the retina with
      photoacoustic ophthalmoscopy and autofluorescence imaging.
AB  - We combined photoacoustic ophthalmoscopy (PAOM) with autofluorescence imaging for
      simultaneous in vivo imaging of dual molecular contrasts in the retina using a
      single light source. The dual molecular contrasts come from melanin and
      lipofuscin in the retinal pigment epithelium (RPE). Melanin and lipofuscin are
      two types of pigments and are believed to play opposite roles (protective versus
      exacerbate) in the RPE in the aging process. We have successfully imaged the
      retina of pigmented and albino rats at different ages. The experimental results
      showed that multimodal PAOM system can be a potentially powerful tool in the
      study of age-related degenerative retinal diseases.

PMID- 21895305
TI  - Reflection-mode time-reversed ultrasonically encoded optical focusing into turbid
      media.
AB  - Time-reversed ultrasonically encoded (TRUE) optical focusing was recently
      proposed to deliver light dynamically to a tight region inside a scattering
      medium. In this letter, we report the first development of a reflection-mode TRUE
      optical focusing system. A high numerical aperture light guide is used to
      transmit the diffusely reflected light from a turbid medium to a phase-conjugate
      mirror (PCM), which is sensitive only to the ultrasound-tagged light. From the
      PCM, a phase conjugated wavefront of the tagged light is generated and conveyed
      by the same light guide back to the turbid medium, subsequently converging to the
      ultrasonic focal zone. We present experimental results from this system, which
      has the ability to focus light in a highly scattering medium with a round-trip
      optical penetration thickness (extinction coefficient multiplied by round-trip
      depth) as large as 160.

PMID- 21895306
TI  - Identification of the direction of the neural network activation with a cellular
      resolution by fast two-photon imaging.
AB  - Spatiotemporal activity patterns in local neural networks are fundamental to
      understanding how information is processed and stored in brain microcircuits.
      Currently, imaging techniques are able to map the directional activation of
      macronetworks across brain areas; however, these strategies still fail to resolve
      the activation direction for fine microcircuits with cellular spatial resolution.
      Here, we show the capability to identify the activation direction of a multicell
      network with a cellular resolution and millisecond precision by using fast two
      photon microscopy and cross correlation procedures. As an example, we
      characterized a directional neuronal network in an epilepsy brain slice to
      provide different initiation delay among multiple neurons defined at a
      millisecond scale.

PMID- 21895307
TI  - Microfluidic sensing: state of the art fabrication and detection techniques.
AB  - Here we introduce the existing fabrication techniques, detection methods, and
      related techniques for microfluidic sensing, with an emphasis on the detection
      techniques. A general survey and comparison of the fabrication techniques were
      given, including prototyping (hot embossing, inject molding, and soft
      lithography) and direct fabrication (laser micromachining, photolithography,
      lithography, and x-ray lithography) techniques. This is followed by an in-depth
      look at detection techniques: optical, electrochemical, mass spectrometry, as
      well as nuclear magnetic resonance spectroscopy-based sensing approaches and
      related techniques. In the end, we highlight several of the most important issues
      for future work on microfluidic sensing. This article aims at providing a
      tutorial review with both introductory materials and inspiring information on
      microfluidic fabrication and sensing for nonspecialists.

PMID- 21895308
TI  - Laser-induced regeneration of cartilage.
AB  - Laser radiation provides a means to control the fields of temperature and thermo
      mechanical stress, mass transfer, and modification of fine structure of the
      cartilage matrix. The aim of this outlook paper is to review physical and
      biological aspects of laser-induced regeneration of cartilage and to discuss the
      possibilities and prospects of its clinical applications. The problems and the
      pathways of tissue regeneration, the types and features of cartilage will be
      introduced first. Then we will review various actual and prospective approaches
      for cartilage repair; consider possible mechanisms of laser-induced regeneration.
      Finally, we present the results in laser regeneration of joints and spine disks
      cartilages and discuss some future applications of lasers in regenerative
      medicine.

PMID- 21895309
TI  - Reflected light intensity profile of two-layer tissues: phantom experiments.
AB  - Experimental measurements of the reflected light intensity from two-layer
      phantoms are presented. We report, for the first time, an experimental
      observation of a typical reflected light intensity behavior for the two-layer
      structure characterized by two different slopes in the reflected light profile of
      the irradiated tissue. The point in which the first slope changes to the second
      slope, named as the crossover point, depends on the upper layer thickness as well
      as on the ratio between the absorption coefficients of the two layers. Since
      similar experiments from one-layer phantoms present a monotonic decay behavior,
      the existence and the location of the crossover point can be used as a diagnostic
      fingerprint for two-layer tissue structures. This pertains to two layers with
      greater absorptivity in the upper layer, which is the typical biological case in
      tissues like skin.

PMID- 21895310
TI  - Influence of phase function on modeled optical response of nanoparticle-labeled
      epithelial tissues.
AB  - Metal nanoparticles can be functionalized with biomolecules to selectively
      localize in precancerous tissues and can act as optical contrast enhancers for
      reflectance-based diagnosis of epithelial precancer. We carry out Monte Carlo
      (MC) simulations to analyze photon propagation through nanoparticle-labeled
      tissues and to reveal the importance of using a proper form of phase function for
      modeling purposes. We first employ modified phase functions generated with a
      weighting scheme that accounts for the relative scattering strengths of unlabeled
      tissue and nanoparticles. To present a comparative analysis, we repeat our MC
      simulations with simplified functions that only approximate the angular
      scattering properties of labeled tissues. The results obtained for common optical
      sensor geometries and biologically relevant labeling schemes indicate that the
      exact form of the phase function used as model input plays an important role in
      determining the reflectance response and approximating functions often prove
      inadequate in predicting the extent of contrast enhancement due to labeling.
      Detected reflectance intensities computed with different phase functions can
      differ up to ~60% and such a significant deviation may even alter the perceived
      contrast profile. These results need to be taken into account when developing
      photon propagation models to assess the diagnostic potential of nanoparticle
      enhanced optical measurements.

PMID- 21895311
TI  - New Monte Carlo model of cylindrical diffusing fibers illustrates axially
      heterogeneous fluorescence detection: simulation and experimental validation.
AB  - We present a new Monte Carlo model of cylindrical diffusing fibers that is
      implemented with a graphics processing unit. Unlike previously published models
      that approximate the diffuser as a linear array of point sources, this model is
      based on the construction of these fibers. This allows for accurate determination
      of fluence distributions and modeling of fluorescence generation and collection.
      We demonstrate that our model generates fluence profiles similar to a linear
      array of point sources, but reveals axially heterogeneous fluorescence detection.
      With axially homogeneous excitation fluence, approximately 90% of detected
      fluorescence is collected by the proximal third of the diffuser for MU(s)'/MU(a)
      = 8 in the tissue and 70 to 88% is collected in this region for MU(s)'/MU(a) =
      80. Increased fluorescence detection by the distal end of the diffuser relative
      to the center section is also demonstrated. Validation of these results was
      performed by creating phantoms consisting of layered fluorescent regions.
      Diffusers were inserted into these layered phantoms and fluorescence spectra were
      collected. Fits to these spectra show quantitative agreement between simulated
      fluorescence collection sensitivities and experimental results. These results
      will be applicable to the use of diffusers as detectors for dosimetry in
      interstitial photodynamic therapy.

PMID- 21895312
TI  - Psychophysics, reliability, and norm values for temporal contrast sensitivity
      implemented on the two alternative forced choice C-Quant device.
AB  - The current paper describes the design and population testing of a flicker
      sensitivity assessment technique corresponding to the psychophysical approach for
      straylight measurement. The purpose is twofold: to check the subjects' capability
      to perform the straylight test and as a test for retinal integrity for other
      purposes. The test was implemented in the Oculus C-Quant straylight meter, using
      homemade software (MATLAB). The geometry of the visual field lay-out was
      identical, as was the subjects' 2AFC task. A comparable reliability criterion
      ("unc") was developed. Outcome measure was logTCS (temporal contrast
      sensitivity). The population test was performed in science fair settings on about
      400 subjects. Moreover, 2 subjects underwent extensive tests to check whether
      optical defects, mimicked with trial lenses and scatter filters, affected the TCS
      outcome. Repeated measures standard deviation was 0.11 log units for the
      reference population. Normal values for logTCS were around 2 (threshold 1%) with
      some dependence on age (range 6 to 85 years). The test outcome did not change
      upon a tenfold (optical) deterioration in visual acuity or straylight. The test
      has adequate precision for checking a subject's capability to perform straylight
      assessment. The unc reliability criterion ensures sufficient precision, also for
      assessment of retinal sensitivity loss.

PMID- 21895313
TI  - Quasi-real-time fluorescence imaging with lifetime dependent contrast.
AB  - Conventional fluorescence lifetime imaging requires complicated algorithms to
      extract lifetimes of fluorophores and acquisition of multiple data points at
      progressively longer delay times to characterize tissues. To address diminishing
      signal-to-noise ratios at these progressively longer time delays, we report a
      time-resolved fluorescence imaging method, normalized fluorescence yield imaging
      that does not require the extraction of lifetimes. The concept is to extract the
      "contrast" instead of the lifetime value of the fluorophores by using simple
      mathematical algorithms. This process converts differences in decay times
      directly to different intensities. The technique was verified experimentally
      using a gated iCCD camera and an ultraviolet light-emitting diode light source.
      It was shown that this method can distinguish between chemical dyes (Fluorescein
      and Rhodamine-B) and biomedical samples, such as powders of elastin and collagen.
      Good contrast was obtained between fluorophores that varied by less than 6% in
      lifetime. Additionally, it was shown that long gate times up to 16 ns achieve
      good contrast depending upon the samples to be studied. These results support the
      feasibility of time-resolved fluorescence imaging without lifetime extraction,
      which has a potential clinical role in noninvasive real-time imaging.

PMID- 21895314
TI  - On the use of frequency-domain reconstruction algorithms for photoacoustic
      imaging.
AB  - We investigate the use of a frequency-domain reconstruction algorithm based on
      the nonuniform fast Fourier transform (NUFFT) for photoacoustic imaging (PAI).
      Standard algorithms based on the fast Fourier transform (FFT) are computationally
      efficient, but compromise the image quality by artifacts. In our previous work we
      have developed an algorithm for PAI based on the NUFFT which is computationally
      efficient and can reconstruct images with the quality known from temporal
      backprojection algorithms. In this paper we review imaging qualities, such as
      resolution, signal-to-noise ratio, and the effects of artifacts in real-world
      situations. Reconstruction examples show that artifacts are reduced
      significantly. In particular, image details with a larger distance from the
      detectors can be resolved more accurately than with standard FFT algorithms.

PMID- 21895315
TI  - Two-dimensional and three-dimensional viability measurements of adult stem cells
      with optical coherence phase microscopy.
AB  - Cell viability assays are essential tools for cell biology. They assess healthy
      cells in a sample and enable the quantification of cellular responses to reagents
      of interest. Noninvasive and label-free assays are desirable in two-dimensional
      (2D) and three-dimensional (3D) cell culture to facilitate time-course viability
      studies. Cellular micromotion, emanating from cell to substrate distance
      variations, has been demonstrated as a marker of cell viability with electric
      cell-substrate impedance sensing (ECIS). In this study we investigated if optical
      coherence phase microscopy (OCPM) was able to report phase fluctuations of adult
      stem cells in 2D and 3D that could be associated with cellular micromotion. An
      OCPM has been developed around a Thorlabs engine (lambdao = 930 nm) and
      integrated in an inverted microscope with a custom scanning head. Human adipose
      derived stem cells (ADSCs, Invitrogen) were cultured in Mesenpro RS medium and
      seeded either on ECIS arrays, 2D cell culture dishes, or in 3D highly porous
      microplotted polymeric scaffolds. ADSC micromotion was confirmed by ECIS
      analysis. Live and fixed ADSCs were then investigated in 2D and 3D with OCPM.
      Significant differences were found in phase fluctuations between the different
      conditions. This study indicated that OCPM could potentially assess cell vitality
      in 2D and in 3D microstructures.

PMID- 21895316
TI  - Ultrahigh sensitive optical microangiography reveals depth-resolved
      microcirculation and its longitudinal response to prolonged ischemic event within
      skeletal muscles in mice.
AB  - The primary pathophysiology of peripheral arterial disease is associated with
      impaired perfusion to the muscle tissue in the lower extremities. The lack of
      effective pharmacologic treatments that stimulate vessel collateralization
      emphasizes the need for an imaging method that can be used to dynamically
      visualize depth-resolved microcirculation within muscle tissues. Optical
      microangiography (OMAG) is a recently developed label-free imaging method capable
      of producing three-dimensional images of dynamic blood perfusion within
      microcirculatory tissue beds at an imaging depth of up to ~2 mm, with an
      unprecedented imaging sensitivity of blood flow at ~4 MUm/s. In this paper, we
      demonstrate the utility of OMAG in imaging the detailed blood flow distributions,
      at a capillary-level resolution, within skeletal muscles of mice. By use of the
      mouse model of hind-limb ischemia, we show that OMAG can assess the time
      dependent changes in muscle perfusion and perfusion restoration along tissue
      depth. These findings indicate that OMAG can represent a sensitive, consistent
      technique to effectively study pharmacologic therapies aimed at promoting the
      growth and development of collateral vessels.

PMID- 21895318
TI  - Transverse chemical interface detection with coherent anti-Stokes Raman
      scattering microscopy.
AB  - Transverse "chemical" interfaces are revealed with a conventional two beam
      narrowband coherent anti-Stokes Raman scattering microscopy setup in a collinear
      configuration. The exciting "pump" and "Stokes" beams are focused on the sample
      in two opposite directions. The subtraction of the two generated anti-Stokes
      signals gives rise to a signal that is directly proportional to the pure Raman
      spectrum of the resonant medium. This property is used to highlight an interface
      between glass and N,N-dimethylformamide (DMF) and recover the pure Raman spectrum
      of DMF around its 1408 cm(-1) vibrational band.

PMID- 21895317
TI  - Polarization memory effect in optical coherence tomography and dental imaging
      application.
AB  - We report the existence of polarization memory effect (PME) in optical coherence
      tomography and investigate its potential applications in dental imaging. We
      performed the study in three steps. First, microsphere scattering phantoms of
      different sizes were imaged in order to validate experimental results with PME
      theory. Both linearly and circularly polarized light were used to probe the
      samples. Second, healthy tooth samples were scanned and polarization memory
      effect was identified in dentin. In this step, specific verification and signal
      processing were performed to rule out possible image interpretation by
      birefringence effect. Third, we evaluated dentin demineralization with PME.
      Results show polarization memory can be useful to characterize this dynamic
      mineralization process for early caries detection and rehabilitation.

PMID- 21895319
TI  - Photon budget analysis for fluorescence lifetime imaging microscopy.
AB  - We have constructed a mathematical model to analyze the photon efficiency of
      frequency-domain fluorescence lifetime imaging microscopy (FLIM). The power of
      the light source needed for illumination in a FLIM system and the signal-to-noise
      ratio of the detector have led us to a photon "budget." These measures are
      relevant to many fluorescence microscope users and the results are not restricted
      to FLIM but applicable to widefield fluorescence microscopy in general.
      Limitations in photon numbers, however, are more of an issue with FLIM compared
      to other less quantitative types of imaging. By modeling a typical experimental
      configuration, examples are given for fluorophores whose absorption peaks span
      the visible spectrum from Fura-2 to Cy5. We have performed experiments to
      validate the assumptions and parameters used in our mathematical model. The
      influence of fluorophore concentration on the intensity of the fluorescence
      emission light and the Poisson distribution assumption of the detected
      fluorescence emission light have been validated. The experimental results agree
      well with the mathematical model. This photon budget is important in order to
      characterize the constraints involved in current fluorescent microscope systems
      that are used for lifetime as well as intensity measurements and to design and
      fabricate new systems.

PMID- 21895320
TI  - Differential optical spectropolarimetric imaging system assisted by liquid
      crystal devices for skin imaging.
AB  - Skin cancer diagnosis depends not only on histopathological examination but also
      on visual inspection before and after the excision of suspected lesion. Neoplasm
      is accompanied with changes in birefringence of collagen, pleomorphicity, and
      hyperchromatic state of epithelial nuclei. These phenomena can be measured by
      spectral and polarization changes of light backscattered by the examined tissue.
      A new differential spectropolarimetric system is proposed using liquid crystal
      devices, one as a tunable filter and the other as a polarization rotator, both
      operating at wide spectral ranges from the visible to the near-infrared. Since
      collagen's fibrils texture orientation depends on its location in the skin and
      since it is not well organized, our system scans the bipolarization states by
      continuously rotating the linearly polarized light incident on a skin lesion, and
      collecting differential contrasts between sequenced images when simultaneously
      averaging the statistical readout of a video camera. This noninvasive method
      emphasizes areas on skin where the neoplasm, or tumor, minimizes the statistical
      polarization change of the scattered light from the lesion. The module can be
      considered as an assistant tool for epiluminescence microscopy. Images of skin
      tumors were captured in vivo before the patients having their surgery and
      compared to histopathological results.

PMID- 21895321
TI  - Time-reversed ultrasonically encoded optical focusing into tissue-mimicking media
      with thickness up to 70 mean free paths.
AB  - In turbid media such as biological tissue, multiple scattering hinders direct
      light focusing at depths beyond one transport mean free path. As a solution to
      this problem, time-reversed ultrasonically encoded (TRUE) optical focusing is
      proposed based on ultrasonic encoding of diffused laser light and optical time
      reversal. In TRUE focusing, a laser beam of long coherence length illuminates a
      turbid medium, where the incident light undergoes multiple scattering and part of
      it gets ultrasonically encoded within the ultrasonic focal zone. A conjugated
      wavefront of the ultrasonically encoded light is then generated by a phase
      conjugate mirror outside the medium, which traces back the trajectories of the
      ultrasonically encoded diffused light and converges light to the ultrasonic focal
      zone. Here, we report the latest experimental improvement in TRUE optical
      focusing that increases its penetration in tissue-mimicking media from a
      thickness of 3.75 to 7.00 mm. We also demonstrate that the TRUE focus depends on
      the focal diameter of the ultrasonic transducer.

PMID- 21895322
TI  - Localization of an absorber in a turbid semi-infinite medium by spatially
      resolved continuous-wave diffuse reflectance measurements.
AB  - A method to locate an absorber embedded in a semi-infinite turbid medium by
      spatially-resolved continuous-wave (SRCW) diffuse reflectance measurements is
      introduced. The depth of the absorber is assessed by single wavelength SRCW
      diffuse reflectance measurements by two detectors in a radial row. The ratio of
      perturbations introduced by the defect at two detectors is used to be matched
      with the ratio-versus-depth curve, which are generated by approximate formulas of
      continuous wave diffuse reflectance. The error due to approximation and the error
      in depth assessment are studied for different cases revealing favorable source
      detector placements with respect to planar position of the defect. The effect of
      lateral displacement of the source with respect to defect is studied. A strategy
      to overcome errors introduced by erroneous prediction of background medium
      optical properties is suggested. Theoretical results indicate that the depth of
      the absorber can be obtained with 0.1 mm precision independent of its absorption
      coefficient and its size for the values chosen in the study. The approach is
      tested experimentally and it is observed that theoretical results fit with
      experimental data.

PMID- 21895323
TI  - Functional laser speckle imaging of cerebral blood flow under hypothermia.
AB  - Hypothermia can unintentionally occur in daily life, e.g., in cardiovascular
      surgery or applied as therapeutics in the neurosciences critical care unit. So
      far, the temperature-induced spatiotemporal responses of the neural function have
      not been fully understood. In this study, we investigated the functional change
      in cerebral blood flow (CBF), accompanied with neuronal activation, by laser
      speckle imaging (LSI) during hypothermia. Laser speckle images from Sprague
      Dawley rats (n = 8, male) were acquired under normothermia (37 degrees C) and
      moderate hypothermia (32 degrees C). For each animal, 10 trials of electrical
      hindpaw stimulation were delivered under both temperatures. Using registered
      laser speckle contrast analysis and temporal clustering analysis (TCA), we found
      a delayed response peak and a prolonged response window under hypothermia.
      Hypothermia also decreased the activation area and the amplitude of the peak CBF.
      The combination of LSI and TCA is a high-resolution functional imaging method to
      investigate the spatiotemporal neurovascular coupling in both normal and
      pathological brain functions.

PMID- 21895324
TI  - Noninvasive imaging of human skin hemodynamics using a digital red-green-blue
      camera.
AB  - In order to visualize human skin hemodynamics, we investigated a method that is
      specifically developed for the visualization of concentrations of oxygenated
      blood, deoxygenated blood, and melanin in skin tissue from digital RGB color
      images. Images of total blood concentration and oxygen saturation can also be
      reconstructed from the results of oxygenated and deoxygenated blood. Experiments
      using tissue-like agar gel phantoms demonstrated the ability of the developed
      method to quantitatively visualize the transition from an oxygenated blood to a
      deoxygenated blood in dermis. In vivo imaging of the chromophore concentrations
      and tissue oxygen saturation in the skin of the human hand are performed for 14
      subjects during upper limb occlusion at 50 and 250 mm Hg. The response of the
      total blood concentration in the skin acquired by this method and forearm volume
      changes obtained from the conventional strain-gauge plethysmograph were
      comparable during the upper arm occlusion at pressures of both 50 and 250 mm Hg.
      The results presented in the present paper indicate the possibility of
      visualizing the hemodynamics of subsurface skin tissue.

PMID- 21895325
TI  - Multiphoton microscopy and fluorescence lifetime imaging provide a novel method
      in studying drug distribution and metabolism in the rat liver in vivo.
AB  - Multiphoton microscopy has been shown to be a useful tool in studying drug
      distribution in biological tissues. In addition, fluorescence lifetime imaging
      provides information about the structure and dynamics of fluorophores based on
      their fluorescence lifetimes. Fluorescein, a commonly used fluorescent probe, is
      metabolized within liver cells to fluorescein mono-glucuronide, which is also
      fluorescent. Fluorescein and its glucuronide have similar excitation and emission
      spectra, but different fluorescence lifetimes. In this study, we employed
      multiphoton fluorescence lifetime imaging to study the distribution and
      metabolism of fluorescein and its metabolite in vivo in rat liver. Fluorescence
      lifetime values in vitro were used to interpret in vivo data. Our results show
      that the mean fluorescence lifetimes of fluorescein and its metabolite decrease
      over time after injection of fluorescein in three different regions of the liver.
      In conclusion, we have demonstrated a novel method to study a fluorescent
      compound and metabolite in vivo using multiphoton fluorescence lifetime imaging.

PMID- 21895326
TI  - Transillumination hyperspectral imaging for histopathological examination of
      excised tissue.
AB  - Angular domain spectroscopic imaging (ADSI) is a novel technique for the
      detection and characterization of optical contrast in turbid media based on
      spectral characteristics. The imaging system employs a silicon micromachined
      angular filter array to reject scattered light traversing a specimen and an
      imaging spectrometer to capture and discriminate the largely remaining
      quasiballistic light based on spatial position and wavelength. The imaging
      modality results in hyperspectral shadowgrams containing two-dimensional (2D)
      spatial maps of spectral information. An ADSI system was constructed and its
      performance was evaluated in the near-infrared region on tissue-mimicking
      phantoms. Image-based spectral correlation analysis using transmission spectra
      and first order derivatives revealed that embedded optical targets could be
      resolved. The hyperspectral images obtained with ADSI were observed to depend on
      target concentration, target depth, and scattering level of the background
      medium. A similar analysis on a muscle and tumor sample dissected from a mouse
      resulted in spatially dependent optical transmission spectra that were distinct,
      which suggested that ADSI may find utility in classifying tissues in biomedical
      applications.

PMID- 21895328
TI  - Classification of change detection and change blindness from near-infrared
      spectroscopy signals.
AB  - Using a machine-learning classification algorithm applied to near-infrared
      spectroscopy (NIRS) signals, we classify a success (change detection) or a
      failure (change blindness) in detecting visual changes for a change-detection
      task. Five subjects perform a change-detection task, and their brain activities
      are continuously monitored. A support-vector-machine algorithm is applied to
      classify the change-detection and change-blindness trials, and correct
      classification probability of 70-90% is obtained for four subjects. Two types of
      temporal shapes in classification probabilities are found: one exhibiting a
      maximum value after the task is completed (postdictive type), and another
      exhibiting a maximum value during the task (predictive type). As for the
      postdictive type, the classification probability begins to increase immediately
      after the task completion and reaches its maximum in about the time scale of
      neuronal hemodynamic response, reflecting a subjective report of change
      detection. As for the predictive type, the classification probability shows an
      increase at the task initiation and is maximal while subjects are performing the
      task, predicting the task performance in detecting a change. We conclude that
      decoding change detection and change blindness from NIRS signal is possible and
      argue some future applications toward brain-machine interfaces.

PMID- 21895327
TI  - First-in-human pilot study of a spatial frequency domain oxygenation imaging
      system.
AB  - Oxygenation measurements are widely used in patient care. However, most
      clinically available instruments currently consist of contact probes that only
      provide global monitoring of the patient (e.g., pulse oximetry probes) or local
      monitoring of small areas (e.g., spectroscopy-based probes). Visualization of
      oxygenation over large areas of tissue, without a priori knowledge of the
      location of defects, has the potential to improve patient management in many
      surgical and critical care applications. In this study, we present a clinically
      compatible multispectral spatial frequency domain imaging (SFDI) system optimized
      for surgical oxygenation imaging. This system was used to image tissue
      oxygenation over a large area (16*12 cm) and was validated during preclinical
      studies by comparing results obtained with an FDA-approved clinical oxygenation
      probe. Skin flap, bowel, and liver vascular occlusion experiments were performed
      on Yorkshire pigs and demonstrated that over the course of the experiment,
      relative changes in oxygen saturation measured using SFDI had an accuracy within
      10% of those made using the FDA-approved device. Finally, the new SFDI system was
      translated to the clinic in a first-in-human pilot study that imaged skin flap
      oxygenation during reconstructive breast surgery. Overall, this study lays the
      foundation for clinical translation of endogenous contrast imaging using SFDI.

PMID- 21895329
TI  - Estimating and validating the interbeat intervals of the heart using near
      infrared spectroscopy on the human forehead.
AB  - In studies with near-infrared spectroscopy, the recorded signals contain
      information on the temporal interbeat intervals of the heart. If this cardiac
      information is needed exclusively and could directly be extracted, an additional
      electrocardiography device would be unnecessary. The aim was to estimate these
      intervals from signals measured with near-infrared spectroscopy with two novel
      approaches. In one approach, we model the heartbeat oscillations in these signals
      with a Fourier series where the coefficients and the fundamental frequency can
      continuously change over time. The time-dependent model parameters are estimated
      and used to calculate the interbeat intervals. The second approach uses empirical
      mode decomposition. The signal measured with near-infrared spectroscopy is
      empirically decomposed into a set of oscillatory components. The sum of a
      specific subset of them is an estimate of the pure heartbeat signal in which the
      diastolic peaks and consequential interbeat intervals are detected. We show in
      simultaneous electrocardiography and near-infrared spectroscopy measurements on
      11 subjects (8 men and 3 woman with mean age 32.8 +/- 8.1 yr), that the interbeat
      intervals (and the consequential pulse rate variability measures), estimated
      using the proposed approaches, are in high agreement with their correspondents
      from electrocardiography.

PMID- 21895330
TI  - Distinguishing autofluorescence of normal, benign, and cancerous breast tissues
      through wavelet domain correlation studies.
AB  - Using the multiresolution ability of wavelets and effectiveness of singular value
      decomposition (SVD) to identify statistically robust parameters, we find a number
      of local and global features, capturing spectral correlations in the co- and
      cross-polarized channels, at different scales (of human breast tissues). The
      copolarized component, being sensitive to intrinsic fluorescence, shows different
      behavior for normal, benign, and cancerous tissues, in the emission domain of
      known fluorophores, whereas the perpendicular component, being more prone to the
      diffusive effect of scattering, points out differences in the Kernel-Smoother
      density estimate employed to the principal components, between malignant, normal,
      and benign tissues. The eigenvectors, corresponding to the dominant eigenvalues
      of the correlation matrix in SVD, also exhibit significant differences between
      the three tissue types, which clearly reflects the differences in the spectral
      correlation behavior. Interestingly, the most significant distinguishing feature
      manifests in the perpendicular component, corresponding to porphyrin emission
      range in the cancerous tissue. The fact that perpendicular component is strongly
      influenced by depolarization, and porphyrin emissions in cancerous tissue has
      been found to be strongly depolarized, may be the possible cause of the above
      observation.

PMID- 21895331
TI  - Holographic tissue dynamics spectroscopy.
AB  - Tissue dynamics spectroscopy uses digital holography as a coherence gate to
      extract depth-resolved quasi-elastic dynamic light scattering from inside
      multicellular tumor spheroids. The temporal speckle contrast provides endogenous
      dynamical images of proliferating and hypoxic or necrotic tissues. Fluctuation
      spectroscopy similar to diffusing wave spectroscopy is performed on the dynamic
      speckle to generate tissue-response spectrograms that track time-resolved changes
      in intracellular motility in response to environmental perturbations. The
      spectrograms consist of several frequency bands that range from 0.005 to 5 Hz.
      The fluctuation spectral density and temporal autocorrelations show the signature
      of constrained anomalous diffusion, but with large fluctuation amplitudes caused
      by active processes far from equilibrium. Differences in the tissue-response
      spectrograms between the proliferating outer shell and the hypoxic inner core
      differentiate normal from starved conditions. The differential spectrograms
      provide an initial library of tissue-response signatures to environmental
      conditions of temperature, osmolarity, pH, and serum growth factors.

PMID- 21895332
TI  - Accelerometer-based method for correcting signal baseline changes caused by
      motion artifacts in medical near-infrared spectroscopy.
AB  - In medical near-infrared spectroscopy (NIRS), movements of the subject often
      cause large step changes in the baselines of the measured light attenuation
      signals. This prevents comparison of hemoglobin concentration levels before and
      after movement. We present an accelerometer-based motion artifact removal
      (ABAMAR) algorithm for correcting such baseline motion artifacts (BMAs). ABAMAR
      can be easily adapted to various long-term monitoring applications of NIRS. We
      applied ABAMAR to NIRS data collected in 23 all-night sleep measurements and
      containing BMAs from involuntary movements during sleep. For reference, three
      NIRS researchers independently identified BMAs from the data. To determine
      whether the use of an accelerometer improves BMA detection accuracy, we compared
      ABAMAR to motion detection based on peaks in the moving standard deviation (SD)
      of NIRS data. The number of BMAs identified by ABAMAR was similar to the number
      detected by the humans, and 79% of the artifacts identified by ABAMAR were
      confirmed by at least two humans. While the moving SD of NIRS data could also be
      used for motion detection, on average 2 out of the 10 largest SD peaks in NIRS
      data each night occurred without the presence of movement. Thus, using an
      accelerometer improves BMA detection accuracy in NIRS.

PMID- 21895333
TI  - Habits with killer instincts: in vivo analysis on the severity of oral mucosal
      alterations using autofluorescence spectroscopy.
AB  - Oral habits like chewing and smoking are main causes of oral cancer, which has a
      higher mortality rate than many other cancer forms. Currently, the long term
      survival rate of oral cancer is less than 50%, as a majority of cases are
      detected very late. The clinician's main challenge is to differentiate among a
      multitude of red, white, or ulcerated lesions. Hence, new noninvasive, reliable,
      and fast techniques for the discrimination of oral cavity disorders are to be
      developed. This study includes autofluorescence spectroscopic screening of normal
      volunteers with and without lifestyle oral habits and patients with oral
      submucous fibrosis (OSF). The spectra from different sites of habitues, non
      habitues, and OSF patients were analyzed using the intensity ratio, redox ratio,
      and linear discriminant analysis (LDA). The spectral disparities among these
      groups are well demonstrated in the emission regions of collagen and Flavin
      adenine dinucleotide. We observed that LDA gives better efficiency of
      classification than the intensity ratio technique. Even the differentiation of
      habitues and non-habitues could be well established with LDA. The study concludes
      that the clinical application of autofluorescence spectroscopy along with LDA,
      yields spontaneous screening among individuals, facilitating better patient
      management for clinicians and better quality of life for patients.

PMID- 21895334
TI  - Efficient determination of the epidermal optical properties using a diffusion
      model-based approach: Monte Carlo studies.
AB  - In our previous studies, we have shown that the diffusing probe geometry can be
      used in conjunction with a two-layer diffusion model to accurately recover the
      absorption and scattering properties of skin in vivo. By modifying the original
      design to the diffusing probe with planar source (DPPS) geometry, we have also
      demonstrated that the efficiency of the accompanying multilayer diffusion model
      is comparable to that of a standard semi-infinite diffusion model; thus, precise
      quantification of superficial tissue optical properties in real time using a
      diffusion model becomes possible. In this study, the performance of the DPPS
      diffusion model is evaluated using Monte Carlo simulations and phantom
      measurements. It is found that the DPPS geometry is advantageous over the
      conventional planar source illumination geometry in interrogating superficial
      volumes of samples. In addition, our simulation results have shown that the DPPS
      geometry is capable of accurately recovering the optical properties of 50-MUm
      thick epidermis and could be very useful in detecting cutaneous melanoma that has
      a radius as small as 250 MUm.

PMID- 21895335
TI  - Development of motion resistant instrumentation for ambulatory near-infrared
      spectroscopy.
AB  - Ambulatory near-infrared spectroscopy (aNIRS) enables recording of systemic or
      tissue-specific hemodynamics and oxygenation during a person's normal activities.
      It has particular potential for the diagnosis and management of health problems
      with unpredictable and transient hemodynamic symptoms, or medical conditions
      requiring continuous, long-duration monitoring. aNIRS is also needed in
      conditions where regular monitoring or imaging cannot be applied, including
      remote environments such as during spaceflight or at high altitude. One key to
      the successful application of aNIRS is reducing the impact of motion artifacts in
      aNIRS recordings. In this paper, we describe the development of a novel prototype
      aNIRS monitor, called NINscan, and our efforts to reduce motion artifacts in
      aNIRS monitoring. Powered by 2 AA size batteries and weighting 350 g, NINscan
      records NIRS, ECG, respiration, and acceleration for up to 14 h at a 250 Hz
      sampling rate. The system's performance and resistance to motion is demonstrated
      by long term quantitative phantom tests, Valsalva maneuver tests, and
      multiparameter monitoring during parabolic flight and high altitude hiking. To
      the best of our knowledge, this is the first report of multiparameter aNIRS
      monitoring and its application in parabolic flight.

PMID- 21895336
TI  - Wavelength selection-based nonlinear calibration for transcutaneous blood glucose
      sensing using Raman spectroscopy.
AB  - While Raman spectroscopy provides a powerful tool for noninvasive and real time
      diagnostics of biological samples, its translation to the clinical setting has
      been impeded by the lack of robustness of spectroscopic calibration models and
      the size and cumbersome nature of conventional laboratory Raman systems. Linear
      multivariate calibration models employing full spectrum analysis are often misled
      by spurious correlations, such as system drift and covariations among
      constituents. In addition, such calibration schemes are prone to overfitting,
      especially in the presence of external interferences that may create
      nonlinearities in the spectra-concentration relationship. To address both of
      these issues we incorporate residue error plot-based wavelength selection and
      nonlinear support vector regression (SVR). Wavelength selection is used to
      eliminate uninformative regions of the spectrum, while SVR is used to model the
      curved effects such as those created by tissue turbidity and temperature
      fluctuations. Using glucose detection in tissue phantoms as a representative
      example, we show that even a substantial reduction in the number of wavelengths
      analyzed using SVR lead to calibration models of equivalent prediction accuracy
      as linear full spectrum analysis. Further, with clinical datasets obtained from
      human subject studies, we also demonstrate the prospective applicability of the
      selected wavelength subsets without sacrificing prediction accuracy, which has
      extensive implications for calibration maintenance and transfer. Additionally,
      such wavelength selection could substantially reduce the collection time of
      serial Raman acquisition systems. Given the reduced footprint of serial Raman
      systems in relation to conventional dispersive Raman spectrometers, we anticipate
      that the incorporation of wavelength selection in such hardware designs will
      enhance the possibility of miniaturized clinical systems for disease diagnosis in
      the near future.

PMID- 21895337
TI  - Diagnosis of breast cancer using diffuse optical spectroscopy from 500 to 1600
      nm: comparison of classification methods.
AB  - We report on the use of diffuse optical spectroscopy analysis of breast spectra
      acquired in the wavelength range from 500 to 1600 nm with a fiber optic probe. A
      total of 102 ex vivo samples of five different breast tissue types, namely
      adipose, glandular, fibroadenoma, invasive carcinoma, and ductal carcinoma in
      situ from 52 patients were measured. A model deriving from the diffusion theory
      was applied to the measured spectra in order to extract clinically relevant
      parameters such as blood, water, lipid, and collagen volume fractions, beta
      carotene concentration, average vessels radius, reduced scattering amplitude, Mie
      slope, and Mie-to-total scattering fraction. Based on a classification and
      regression tree algorithm applied to the derived parameters, a sensitivity
      specificity of 98%-99%, 84%-95%, 81%-98%, 91%-95%, and 83%-99% were obtained for
      discrimination of adipose, glandular, fibroadenoma, invasive carcinoma, and
      ductal carcinoma in situ, respectively; and a multiple classes overall diagnostic
      performance of 94%. Sensitivity-specificity values obtained for discriminating
      malignant from nonmalignant tissue were compared to existing reported studies by
      applying the different classification methods that were used in each of these
      studies. Furthermore, in these reported studies, either lipid or beta-carotene
      was considered as adipose tissue precursors. We estimate both chromophore
      concentrations and demonstrate that lipid is a better discriminator for adipose
      tissue than beta-carotene.

PMID- 21895338
TI  - Genetically encoded ratiometric biosensors to measure intracellular exchangeable
      zinc in Escherichia coli.
AB  - Zinc is an essential element for numerous cellular processes, therefore zinc
      homeostasis is regulated in living organisms. Fluorescent sensors have been
      developed as important tools to monitor the concentrations of readily
      exchangeable zinc in live cells. One type of biosensor uses carbonic anhydrase
      (CA) as the recognition element based on its tunable affinity, superior metal
      selectivity, and fluorescence signal from aryl sulfonamide ligands coupled to
      zinc binding. Here, we fuse carbonic anhydrase with a red fluorescent protein to
      create a series of genetically-encoded Forster resonance energy transfer-based
      excitation ratiometric zinc sensors that exhibit large signal increases in
      response to alterations in physiological-free zinc concentrations. These sensors
      were applied to the prokaryotic model organism Escherichia coli to quantify the
      readily exchangeable zinc concentration. In minimal media, E. coli BL21(DE3)
      cells expressing the CA sensor, exhibit a median intracellular readily
      exchangeable zinc concentration of 20 pM, much less than the total cellular zinc
      concentration of ~0.2 mM. Furthermore, the intracellular readily exchangeable
      zinc concentration varies with the concentration of environmental zinc.

PMID- 21895339
TI  - Raman spectroscopy detects deterioration in biomechanical properties of bone in a
      glucocorticoid-treated mouse model of rheumatoid arthritis.
AB  - Although glucocorticoids are frequently prescribed for the symptomatic management
      of inflammatory disorders such as rheumatoid arthritis, extended glucocorticoid
      exposure is the leading cause of physician-induced osteoporosis and leaves
      patients at a high risk of fracture. To study the biochemical effects of
      glucocorticoid exposure and how they might affect biomechanical properties of the
      bone, Raman spectra were acquired from ex vivo tibiae of glucocorticoid- and
      placebo-treated wild-type mice and a transgenic mouse model of rheumatoid
      arthritis. Statistically significant spectral differences were observed due to
      both treatment regimen and mouse genotype. These differences are attributed to
      changes in the overall bone mineral composition, as well as the degree of
      phosphate mineralization in tibial cortical bone. In addition, partial least
      squares regression was used to generate a Raman-based prediction of each tibia's
      biomechanical strength as quantified by a torsion test. The Raman-based
      predictions were as accurate as those produced by microcomputed tomography
      derived parameters, and more accurate than the clinically-used parameter of bone
      mineral density. These results suggest that Raman spectroscopy could be a
      valuable tool for monitoring bone biochemistry in studies of bone diseases such
      as osteoporosis, including tests of drugs being developed to combat these
      diseases.

PMID- 21895340
TI  - Correlation of functional and resting state connectivity of cerebral oxy-, deoxy
      , and total hemoglobin concentration changes measured by near-infrared
      spectrophotometry.
AB  - The aim is to study cerebral vascular functional connectivity during motor tasks
      and resting state using multichannel frequency-domain near-infrared
      spectrophotometry. Maps of 5.7 * 10.8 cm size displaying changes in cerebral
      oxyhemoglobin (O(2)Hb), deoxyhemoglobin (HHb), and total hemoglobin (tHb)
      concentrations were measured in the motor cortex in 12 subjects (mean age of
      28.8+/-12.7 yrs) during resting state and during two palm squeezing tasks with
      different timing. For each condition, phase plane plots, cross correlation
      functions, and connectivity indices were generated for O(2)Hb, HHb, and tHb. The
      amplitude of the concentration changes in O(2)Hb and HHb depends on the age of
      the subject. We found large regions of connectivity, which were similar for
      resting state and task conditions. This means the spatial relationships during
      resting state, when changes in O(2)Hb, HHb, and tHb corresponded to spontaneous
      oscillations, were correlated to the spatial patterns during the activation
      tasks, when changes in O(2)Hb, HHb, and tHb concentration were related to the
      alternation of stimulation and rest. Thus, the vascular functional connectivity
      was also present during resting state. The findings suggest that the vascular
      response to functional activation may be a nonlinear synchronization phenomenon
      and that resting state processes are more important than previously expected.

PMID- 21895341
TI  - Femtosecond laser-induced fusion of nonadherent cells and two-cell porcine
      embryos.
AB  - Cell fusion is a fundamental biological process that can be artificially induced
      by different methods. Although femtosecond (fs) lasers have been successfully
      employed for cell fusion over the past few years, the underlying mechanisms are
      still unknown. In our experimental study, we investigated the correlation between
      fs laser-induced cell fusion and membrane perforation, and the influence of laser
      parameters on the fusion efficiency of nonadherent HL-60 cells. We found that
      shorter exposure times resulted in higher fusion efficiencies with a maximum of
      21% at 10 ms and 100 mJ/cm(2) (190 mW). Successful cell fusion was indicated by
      the formation of a long-lasting vapor bubble in the irradiated area with an
      average diameter much larger than in cell perforation experiments. With this
      knowledge, we demonstrated, for the first time, the fusion of very large
      parthenogenetic two-cell porcine embryos with high efficiencies of 55% at 20 ms
      and 360 mJ/cm(2) (670 mW). Long-term viability of fused embryos was proven by
      successful development up to the blastocyst stage in 70% of cases with no
      significant difference to controls. In contrast to previous studies, our results
      indicate that fs laser-induced cell fusion occurs when the membrane pore size
      exceeds a critical value, preventing immediate membrane resealing.

PMID- 21895342
TI  - Enhanced laser tissue soldering using indocyanine green chromophore and gold
      nanoshells combination.
AB  - Gold nanoshells (GNs) are new materials that have an optical response dictated by
      the plasmon resonance. The wavelength at which the resonance occurs depends on
      the core and shell sizes. The purposes of this study were to use the combination
      of indocyanine green (ICG) and different concentration of gold nanoshells for
      skin tissue soldering and also to examine the effect of laser soldering
      parameters on the properties of repaired skin. Two mixtures of albumin solder and
      different combinations of ICG and gold nanoshells were prepared. A full thickness
      incision of 2 * 20 mm(2) was made on the surface and after addition of mixtures
      it was irradiated by an 810 nm diode laser at different power densities. The
      changes of tensile strength (sigma(t)) due to temperature rise, number of scan
      (Ns), and scan velocity (Vs) were investigated. The results showed at constant
      laser power density (I), sigma(t) of repaired incisions increases by increasing
      the concentration of gold nanoshells in solder, Ns, and decreasing Vs. It was
      demonstrated that laser soldering using combination of ICG + GNs could be
      practical provided the optothermal properties of the tissue are carefully
      optimized. Also, the tensile strength of soldered skin is higher than skins that
      soldered with only ICG or GNs. In our case, this corresponds to sigma(t) = 1800 g
      cm(-2) at I ~ 47 Wcm(-2), T ~ 85 [ordinal indicator, masculine]C, Ns = 10, and Vs
      = 0.3 mms(-1).

PMID- 21895343
TI  - Clinical use of photodynamic antimicrobial chemotherapy for the treatment of deep
      carious lesions.
AB  - The purpose of this study was to assess photodynamic antimicrobial chemotherapy
      (PACT) via irradiation, using a low power laser associated with a
      photosensitization dye, as an alternative to remove cariogenic microorganisms by
      drilling. Remaining dentinal samples in deep carious lesions on permanent molars
      (n = 26) were treated with 0.01% methylene blue dye and irradiated with a low
      power laser (InGaAIP - indium gallium aluminum phosphide; lambda = 660 nm; 100
      mW; 320 Jcm(-2); 90 s; 9J). Samples of dentin from the pulpal wall region were
      collected with a micropunch before and immediately after PACT and kept in a
      transport medium for microbiological analysis. Samples were cultured in plates of
      Brucella blood agar, Mitis Salivarius Bacitracin agar and Rogosa SL agar to
      determine the total viable bacteria, mutans streptococci and Lactobacillus spp.
      counts, respectively. After incubation, colony-forming units were counted and
      microbial reduction was calculated for each group of bacteria. PACT led to
      statistically significant reductions in mutans streptococci (1.38 log),
      Lactobacillus spp. (0.93 log), and total viable bacteria (0.91 log). This therapy
      may be an appropriate approach for the treatment of deep carious lesions using
      minimally invasive procedures.

PMID- 21895346
TI  - Shame regulation in personality pathology.
AB  - Drawing on extant work on shame and emotion regulation, this article proposes
      that three broad forms of maladaptive shame regulation strategies are fundamental
      in much of personality pathology: Prevention (e.g., dependence, fantasy), used
      preemptively, lessens potential for shame; Escape (e.g., social withdrawal,
      misdirection) reduces current or imminent shame; Aggression, used after shame
      begins, refocuses shame into anger directed at the self (e.g., physical self
      harm) or others (e.g., verbal aggression). This article focuses on the
      contributions of shame regulation to the development and maintenance of
      personality pathology, highlighting how various maladaptive shame regulation
      strategies may lead to personality pathology symptoms, associated features, and
      dimensions. Consideration is also given to the possible shame-related constructs
      necessitating emotion regulation (e.g., shame aversion and proneness) and the
      points in the emotion process when regulation can occur.

PMID- 21895344
TI  - Neural correlates of automatic mood regulation in girls at high risk for
      depression.
AB  - Daughters of depressed mothers are at significantly elevated risk for developing
      a depressive disorder themselves. We have little understanding, however, of the
      specific factors that contribute to this risk. The ability to regulate negative
      affect effectively is critical to emotional and physical health and may play an
      important role in influencing risk for depression. We examined whether never
      disordered daughters whose mothers have experienced recurrent episodes of
      depression during their daughters' lifetime differ from never-disordered
      daughters of never-disordered mothers in their patterns of neural activation
      during a negative mood induction and during automatic mood regulation. Sad mood
      was induced in daughters through the use of film clips; daughters then recalled
      positive autobiographical memories, a procedure shown previously to repair
      negative affect. During the mood induction, high-risk girls exhibited greater
      activation than did low-risk daughters in brain areas that have frequently been
      implicated in the experience of negative affect, including the amygdala and
      ventrolateral prefrontal cortex. In contrast, during automatic mood regulation,
      low-risk daughters exhibited greater activation than did their high-risk
      counterparts in brain areas that have frequently been associated with top-down
      regulation of emotion, including the dorsolateral prefrontal cortex and dorsal
      anterior cingulate cortex. These findings indicate that girls at high and low
      risk for depression differ in their patterns of neural activation both while
      experiencing, and while repairing negative affect, and suggest that anomalies in
      neural functioning precede the onset of a depressive episode.

PMID- 21895347
TI  - 21st birthday drinking and associated physical consequences and behavioral risks.
AB  - Twenty-first birthday celebrations often involve dangerously high levels of
      alcohol consumption, yet little is known about risk factors for excessive
      drinking on this occasion. Participants (N = 150) from a larger prospective study
      who consumed at least one drink during their celebration completed questionnaires
      and semistructured interviews about their 21st birthday within four days after
      the event. Assessments were designed to characterize 21st birthday alcohol use,
      adjusted for alcohol content, as well as situational/contextual factors (e.g.,
      celebration location, peer influence) that contribute to event-level drinking.
      Participants reported an average of 10.85 drinks (9.76 adjusted drinks), with
      experienced drinkers consuming significantly more than relatively naive drinkers
      who had no previous binge or drunken episodes. Men consumed more drinks, whereas
      age of first drunken episode and heavier drinking during the 3-months preceding
      the 21st birthday predicted higher estimated blood alcohol concentrations (eBACs)
      on the 21st birthday. Celebrating in bars and engaging in birthday-specific
      drinking traditions (free drinks at bars) explained additional variance in 21st
      birthday eBACs. Both physical consequences (e.g., blacking out or having a
      hangover) and behavioral risks (e.g., sexually provocative behaviors) were
      prevalent and were predicted by higher eBACs. Together these findings indicate
      that 21st birthday celebrations are associated with heavy drinking and a variety
      of physical consequences and behavioral risks.

PMID- 21895348
TI  - Concurrent drinking and smoking among college students: An event-level analysis.
AB  - Cigarette smoking and drinking commonly co-occur among college students, a
      population that is at high risk for developing alcohol and nicotine use
      disorders. Several studies have been conducted that have examined predictors of
      drinking or smoking to gain a better understanding of the antecedents of engaging
      in these behaviors. Yet, few studies have examined specific factors that
      influence concurrent smoking and drinking in this population. The current study
      used data from a 21-day electronic diary-based study of college students (n=86)
      who engaged in concurrent drinking and smoking to examine event-level
      associations between alcohol use and cigarette smoking in the student's natural
      environment. We specifically focused on within-person analyses of contexts in
      which students reported smoking and drinking simultaneously in comparison to
      contexts in which students reporting drinking without smoking. Situational
      contexts included environmental setting, whether s/he was alone or with others,
      and changes in stress and urges to smoke before initiating drinking. Results
      indicated that students drank more while smoking and smoked three times as many
      cigarettes, on average, during drinking episodes. Being with others at a party or
      a bar was associated with increased odds of smoking while drinking. Likewise,
      increased stress since the prior assessment predicted a greater likelihood of
      smoking while drinking. Based on the findings from the present study, it is
      important for future prevention and intervention efforts to consider social
      settings and heightened stress among students as potential risk factors for
      engaging in concurrent drinking and smoking.

PMID- 21895349
TI  - Do social networks explain 12-step sponsorship effects? A prospective lagged
      mediation analysis.
AB  - Sponsorship is a basic and important part of the 12-step approach to recovery
      from substance abuse (Alcoholics Anonymous, 2005) and research has shown that
      having a sponsor is associated with increased involvement in 12-step programs and
      improved outcomes (Bond, Kaskutas, & Weisner, 2003; Tonigan & Rice, 2010).
      However, little is known about how sponsorship improves outcomes. Given research
      demonstrating bivariate associations between sponsorship and social support for
      abstinence (Majer, Jason, Ferrari, Venable, & Olson, 2002), we hypothesized that
      the association between having a sponsor and increased abstinence outcomes would
      be explained by increases in one's abstinence-based social network. Prospective
      fully lagged mediational analyses did not support this hypothesis and these
      results ran counter to findings of five previous studies (cf. Groh, Jason, &
      Keys, 2008). A review of these studies showed that researchers often used cross
      sectional or partially lagged methods to test mediation and the mediational
      effect of the social network was small in magnitude. Results suggest that the
      prospective association between sponsorship and abstinence is not explained by
      increases in the abstinence-based social network and demonstrate the need for
      future studies to use rigorous and time-lagged methods to test social support for
      abstinence as a mediator of the effects of 12-step involvement.

PMID- 21895350
TI  - Mental health treatment need among pregnant and postpartum women/girls entering
      substance abuse treatment.
AB  - Substance use during pregnancy is widely acknowledged as a major public health
      concern with detrimental effects on both mother and unborn child. Mental health
      issues often co-occur with substance use and may trigger continued use during
      pregnancy or relapse to use postpartum, though little is known about the extent
      of these issues in pregnant and postpartum women entering substance abuse
      treatment. The purpose of this study is: (a) to examine self-reported mental
      health in a population of women and girls who were pregnant in the past year and
      are entering substance abuse treatment, and (b) to determine whether disparity
      exists in mental health treatment received across groups by race and age if a
      treatment need is present. Secondary data analysis was conducted with Global
      Appraisal of Individual Needs (GAIN) data from 502 female adolescents and adults
      who reported having been pregnant in the past year and who completed the GAIN
      upon entry into substance abuse treatment. Participants were compared on
      demographic, diagnostic, and problem severity variables by race and age. Results
      indicate that mental health treatment need is high among the whole pregnant and
      postpartum sample, but African American and Hispanic women and girls are
      receiving less mental health treatment than other groups despite having a need
      for it. No mental health treatment acquisition disparity was found by age.

PMID- 21895351
TI  - Centrality and charisma: comparing how leader networks and attributions affect
      team performance.
AB  - When leaders interact in teams with their subordinates, they build social capital
      that can have positive effects on team performance. Does this social capital
      affect team performance because subordinates come to see the leader as
      charismatic? We answered this question by examining 2 models. First, we tested
      the charisma-to-centrality model according to which the leader's charisma
      facilitates the occupation of a central position in the informal advice network.
      From this central position, the leader positively influences team performance.
      Second, we examined the centrality-to-charisma model according to which charisma
      is attributed to those leaders who are socially active in terms of giving and
      receiving advice. Attributed charisma facilitates increased team performance. We
      tested these 2 models in 2 different studies. In the first study, based on time
      separated, multisource data emanating from members of 56 work teams, we found
      support for the centrality-to-charisma model. Formal leaders who were central
      within team advice networks were seen as charismatic by subordinates, and this
      charisma was associated with high team performance. To clarify how leader network
      centrality affected the emergence of charismatic leadership, we designed Study 2
      in which, for 79 student teams, we measured leader networking activity and leader
      charisma at 2 different points in time and related these variables to team
      performance measured at a third point in time. On the basis of this temporally
      separated data set, we again found support for the centrality-to-charisma model.

PMID- 21895352
TI  - Peer-based control in self-managing teams: linking rational and normative
      influence with individual and group performance.
AB  - The authors use a multilevel framework to introduce peer-based control as a
      motivational state that emerges in self-managing teams. The authors specifically
      describe how peer-based rational control, which is defined as team members
      perceiving the distribution of economic rewards as dependent on input from
      teammates, extends and interacts with the more commonly studied normative control
      force of group cohesion to explain both individual and collective performance in
      teams. On the basis of data from 587 factory workers in 45 self-managing teams at
      3 organizations, peer-based rational control corresponded with higher performance
      for both individuals and collective teams. Results further demonstrated that the
      rational and normative mechanism of peer-based control interacted to explain
      performance at both the individual and team levels. Increased peer-based rational
      control corresponded with higher individual and collective performance in teams
      with low cohesion, but the positive effects on performance were attenuated in
      cohesive teams.

PMID- 21895353
TI  - Facial affect processing and depression susceptibility: cognitive biases and
      cognitive neuroscience.
AB  - Facial affect processing is essential to social development and functioning and
      is particularly relevant to models of depression. Although cognitive and
      interpersonal theories have long described different pathways to depression,
      cognitive-interpersonal and evolutionary social risk models of depression focus
      on the interrelation of interpersonal experience, cognition, and social behavior.
      We therefore review the burgeoning depressive facial affect processing literature
      and examine its potential for integrating disciplines, theories, and research. In
      particular, we evaluate studies in which information processing or cognitive
      neuroscience paradigms were used to assess facial affect processing in depressed
      and depression-susceptible populations. Most studies have assessed and supported
      cognitive models. This research suggests that depressed and depression-vulnerable
      groups show abnormal facial affect interpretation, attention, and memory,
      although findings vary based on depression severity, comorbid anxiety, or length
      of time faces are viewed. Facial affect processing biases appear to correspond
      with distinct neural activity patterns and increased depressive emotion and
      thought. Biases typically emerge in depressed moods but are occasionally found in
      the absence of such moods. Indirect evidence suggests that childhood neglect
      might cultivate abnormal facial affect processing, which can impede social
      functioning in ways consistent with cognitive-interpersonal and interpersonal
      models. However, reviewed studies provide mixed support for the social risk model
      prediction that depressive states prompt cognitive hypervigilance to social
      threat information. We recommend prospective interdisciplinary research examining
      whether facial affect processing abnormalities promote-or are promoted by
      depressogenic attachment experiences, negative thinking, and social dysfunction.

PMID- 21895354
TI  - Perspectives on observational learning in animals.
AB  - Observational learning is presumed to have occurred when an organism copies an
      improbable action or action outcome that it has observed and the matching
      behavior cannot be explained by an alternative mechanism. Psychologists have been
      particularly interested in the form of observational learning known as imitation
      and in how to distinguish imitation from other processes. To successfully make
      this distinction, one must disentangle the degree to which behavioral similarity
      results from (a) predisposed behavior, (b) increased motivation resulting from
      the presence of another animal, (c) attention drawn to a place or object, (d)
      learning about the way the environment works, as distinguished from what we think
      of as (e) imitation (the copying of the demonstrated behavior). Several of the
      processes that may be involved in observational learning are reviewed, including
      social facilitation, stimulus enhancement, several kinds of emulation, and
      various forms of imitation.

PMID- 21895355
TI  - What's social about social learning?
AB  - Research on social learning in animals has revealed a rich variety of cases where
      animals--from caddis fly larvae to chimpanzees--acquire biologically important
      information by observing the actions of others. A great deal is known about the
      adaptive functions of social learning, but very little about the cognitive
      mechanisms that make it possible. Even in the case of imitation, a type of social
      learning studied in both comparative psychology and cognitive science, there has
      been minimal contact between the two disciplines. Social learning has been
      isolated from cognitive science by two longstanding assumptions: that it depends
      on a set of special-purpose modules--cognitive adaptations for social living; and
      that these learning mechanisms are largely distinct from the processes mediating
      human social cognition. Recent research challenges these assumptions by showing
      that social learning covaries with asocial learning; occurs in solitary animals;
      and exhibits the same features in diverse species, including humans. Drawing on
      this evidence, I argue that social and asocial learning depend on the same basic
      learning mechanisms; these are adapted for the detection of predictive
      relationships in all natural domains; and they are associative mechanisms-
      processes that encode information for long-term storage by forging excitatory and
      inhibitory links between event representations. Thus, human and nonhuman social
      learning are continuous, and social learning is adaptively specialized--it
      becomes distinctively "social"--only when input mechanisms (perceptual,
      attentional, and motivational processes) are phylogenetically or ontogenetically
      tuned to other agents.

PMID- 21895356
TI  - Social connectedness, discrimination, and social status as mediators of
      acculturation/enculturation and well-being.
AB  - The present study proposed and tested a conceptual model of
      acculturation/enculturation and subjective well-being (SWB) by including social
      connectedness in mainstream society, social connectedness in the ethnic
      community, perceived discrimination, and expected social status as mediators.
      Survey data from 273 Asian American college students in the midwest were analyzed
      by using structural equation modeling. Results indicated that the effect of
      acculturation on SWB was mediated by social connectedness in mainstream and
      ethnic communities and expected social status, whereas the effect of
      enculturation on SWB was mediated by social connectedness in the ethnic community
      and expected social status. Contrary to the authors' hypothesis, perceived
      discrimination did not mediate the relation of acculturation and SWB, but
      indirectly influenced SWB via a lowered sense of connectedness to mainstream
      society. Approximately 46% of the variance in SWB was accounted for by the
      variables included in this model. Implications for theory, research, and practice
      are discussed.

PMID- 21895357
TI  - Resilience: enhancing well-being through the positive cognitive triad.
AB  - The present study tested whether the relationships among resilience, life
      satisfaction, and depression could be explained by positive views toward the
      self, the world, and the future (positive cognitive triad). Structural equation
      modeling and mediation analyses were conducted based on 1,419 college students in
      Hong Kong. The model of positive cognitive triad as mediator between resilience
      and well-being fit the data (comparative fit index = .94, Tucker-Lewis index =
      .93, root-mean-square error of approximation = .08). Findings showed resilience
      to be significantly related to positive cognitions about the self, the world, and
      the future. Individuals who had higher level of resilience held significantly
      more positive cognitions and reported significantly higher levels of life
      satisfaction and lower levels of depression. The utility of the positive
      cognitive triad as the mechanism through which resilience enhances well-being was
      supported. Applications in cultivating resilience and positive cognitions in
      counseling services are discussed.

PMID- 21895358
TI  - Future orientation, impulsivity, and problem behaviors: a longitudinal moderation
      model.
AB  - In the current study, based on a sample of 1,873 adolescents between 11.4 and
      20.9 years of age from the first 3 waves of the National Longitudinal Study of
      Adolescent Health, we investigated the longitudinal effects of future orientation
      on levels of and developmental changes in problem behaviors, while controlling
      for the effects by impulsivity; we also tested the moderating effects by future
      orientation on the impulsivity-problem behaviors link over time. Additionally, we
      examined future orientation operationalized by items measuring education,
      marriage, and life domains. Findings based on growth curve analyses provided
      evidence of longitudinal effects by education and life future orientation on both
      levels of and developmental changes in problem behaviors; the effect of marriage
      future orientation was not significant for either test. In addition, only life
      future orientation moderated the effect by impulsivity on levels of problem
      behaviors over time. More specifically, impulsivity had a weaker effect on levels
      of problem behaviors over time for adolescents who reported higher levels of life
      future orientation.

PMID- 21895359
TI  - The role of intersensory redundancy in the emergence of social referencing in
      51/2-month-old infants.
AB  - Early evidence of social referencing was examined in 51/2-month-old infants.
      Infants were habituated to 2 films of moving toys, one toy eliciting a woman's
      positive emotional expression and the other eliciting a negative expression under
      conditions of bimodal (audiovisual) or unimodal visual (silent) speech. It was
      predicted that intersensory redundancy provided by audiovisual (but not available
      in unimodal visual) events would enhance detection of the relation between
      emotional expressions and the corresponding toy. Consistent with predictions,
      only infants who received bimodal, audiovisual events detected a change in the
      affect-object relations, showing increased looking during a switch test in which
      the toy-affect pairing was reversed. Moreover, in a subsequent live preference
      test, they preferentially touched the 3-dimensional toy previously paired with
      the positive expression. These findings suggest social referencing emerges by
      51/2 months in the context of intersensory redundancy provided by dynamic
      multimodal stimulation and that even 51/2-month-old infants demonstrate
      preferences for 3-dimensional objects on the basis of affective information
      depicted in videotaped events.

PMID- 21895360
TI  - Families created through surrogacy: mother-child relationships and children's
      psychological adjustment at age 7.
AB  - Each year, an increasing number of children are born through surrogacy and thus
      lack a genetic and/or gestational link with their mother. This study examined the
      impact of surrogacy on mother-child relationships and children's psychological
      adjustment. Assessments of maternal positivity, maternal negativity, mother-child
      interaction, and child adjustment were administered to 32 surrogacy, 32 egg
      donation, and 54 natural conception families with a 7-year-old child. No
      differences were found for maternal negativity, maternal positivity, or child
      adjustment, although the surrogacy and egg donation families showed less positive
      mother-child interaction than the natural conception families. The findings
      suggest that both surrogacy and egg donation families function well in the early
      school years.

PMID- 21895361
TI  - Longitudinal effects of theory of mind on later peer relations: the role of
      prosocial behavior.
AB  - Children's peer relations represent a key aspect of school adjustment. However,
      little is known about their social-cognitive precursors. To address this gap, the
      authors followed 70 children across the transition to primary school. At Time 1
      (age 5), Time 2 (age 6), and Time 3 (age 7), children were assessed on their
      theory of mind, prosocial behavior, and verbal ability. In addition, at Time 2
      and at Time 3, the authors gathered peer nominations. Results supported the
      authors' mediational hypothesis of indirect paths from early theory of mind to
      subsequently lower peer rejection and higher peer acceptance, via improvements in
      prosocial behavior. The authors discuss implications of these longitudinal
      effects for the understanding of the impact of social-cognitive achievements for
      children's developing social relations.

PMID- 21895362
TI  - The "cost of caring" in youths' friendships: considering associations among
      social perspective taking, co-rumination, and empathetic distress.
AB  - The current research considered the costs of caring in youths' friendships. The
      development of a new construct, empathetic distress, allowed for a direct test of
      the commonly held belief that females suffer greater vicarious distress in
      response to close others' stressors and problems than do males. Empathetic
      distress refers to one's strongly sharing a relationship partner's distress over
      problems to the point of taking on the partner's distress and experiencing it as
      one's own. This new construct was examined in an ethnically diverse sample of
      early adolescents who responded to a series of questionnaires in their
      classrooms. Results indicated that girls did experience greater empathetic
      distress in friendships than did boys. In addition, the current research revealed
      that social perspective taking in friendships (i.e., the social-cognitive ability
      to infer and understand the friend's perspective) had adjustment trade-offs in
      that it predicted greater positive friendship quality but also greater empathetic
      distress in the friendship. Interestingly, the associations of social perspective
      taking with both positive friendship quality and empathetic distress were
      partially mediated by co-rumination or excessive discussion of problems. Applied
      implications of the findings that girls' greater social perspective taking and
      associated co-rumination contributed both to their greater positive friendship
      quality but also to greater costs of caring in the form of empathetic distress
      are discussed.

PMID- 21895363
TI  - The effect of generic statements on children's causal attributions: questions of
      mechanism.
AB  - Generic statements, or generics, express generalizations about entire kinds
      (e.g., "Girls are good at a game called 'tooki'"). In contrast, nongeneric
      statements express facts about specific (sets of) individuals (e.g., "Jane is
      good at tooki"). Aside from simply conveying information, generics and
      nongenerics also instill different causal perspectives on the facts expressed,
      implying that these facts stem from deep, inherent causes (e.g., talent) or from
      external, mechanistic causes (e.g., instruction), respectively. In the present
      research (with samples of 4- to 7-year-olds and undergraduates, N = 220), we
      proposed that children's causal attributions for the facts learned through these
      statements are determined not by the generic/nongeneric format of the statements
      themselves but rather by the generic/nongeneric format of the beliefs relevant to
      these statements. This proposal led to two specific predictions. First, the
      influence of the generic belief induced by a novel generic statement should be
      detected in any subsequent context that falls under its scope--even in
      circumstances that involve particular individuals. Confirming this prediction,
      participants often attributed a fact conveyed in a nongeneric statement (e.g., a
      particular girl's tooki ability) to deep, inherent causes if they had previously
      formed a relevant generic belief (e.g., by hearing that girls are good at tooki).
      Second, we predicted that nongeneric statements such as "Most girls are good at
      tooki" should also promote attributions to deep causes because they often
      ultimately give rise to generic beliefs, as suggested by recent evidence. This
      prediction was confirmed as well. These results clarify and expand our knowledge
      of the influence of language on children's understanding of the world.

PMID- 21895364
TI  - The presence of a best friend buffers the effects of negative experiences.
AB  - The goal of the current study was to examine how the presence of a best friend
      might serve as protection against the effect of negative experiences on global
      self-worth and the hypothalamic-pituitary-adrenocortical axis (HPA axis). A total
      of 103 English-speaking male (n = 55) and female (n = 48) participants from Grade
      5 (M = 10.27 years) and Grade 6 (M = 11.30 years) completed booklets about their
      experiences that occurred 20 min previously and how they felt about themselves at
      the moment, and they provided saliva multiple times per day over the course of 4
      consecutive days. Having a best friend present during an experience significantly
      buffered the effect of the negativity of the experience on cortisol and global
      self-worth. When a best friend was not present, there was a significant increase
      in cortisol and a significant decrease in global self-worth as the negativity of
      the experience increased. When a best friend was present, there was less change
      in cortisol and global self-worth due to the negativity of the experience.

PMID- 21895365
TI  - Infants' joint attention skills predict toddlers' emerging mental state language.
AB  - To assess predictive relations between joint attention skills, intention
      understanding, and mental state vocabulary, 88 children were tested with measures
      of comprehension of gaze and referential pointing, as well as the production of
      declarative gestures and the comprehension and production of imperative gestures,
      at the ages of 7-18 months. Infants' intention-based imitation skills were
      assessed at 12, 15, and 18 months. At the ages of 24 and 36 months, toddlers'
      internal state lexicon was evaluated by parents with a German adaptation of the
      Mental State Language Questionnaire (Olineck & Poulin-Dubois, 2005). Regression
      analyses revealed that 9-months-olds' comprehension of referential pointing
      contributed significantly to the prediction of intention-based imitation skills
      at 15 months, as well as to children's volition and cognition vocabularies at 24
      and 36 months, respectively. Moreover, 12-month-olds' comprehension of an
      imperative motive was shown to selectively predict toddlers' use of volition
      terms at 24 months. Overall, these results provide empirical evidence for both
      general and specific developmental relations between preverbal communication
      skills and mental state language, thus implying developmental continuity within
      the social domain in the first 3 years of life.

PMID- 21895366
TI  - Depleted parental psychological resources as mediators of the association of
      income with adherence and metabolic control.
AB  - For adolescents with Type 1 diabetes, lower family income may be associated with
      poorer diabetes management through depleted parental psychological resources
      (i.e., higher parental depressive symptoms, lower parental acceptance).
      Adolescents (N = 252; 46% male) aged 10-14 years with Type 1 diabetes assessed
      the acceptance of their mother and father (e.g., "gives me the feeling that she
      likes me as I am"; "she doesn't feel she has to make me over into someone else").
      Mothers provided information on family income and demographics. Both mothers and
      fathers reported their depressive symptoms. HbA1c scores were indexed via medical
      records. Lower family income was associated with higher (i.e., worse) HbA1c, more
      mother and father depressive symptoms, and less acceptance from both parents.
      Mediation analyses revealed that the relationship of lower family income with
      metabolic control occurred indirectly through lower maternal and paternal
      acceptance and lower adherence. Lower family income may impair the quality of
      parent--adolescent relationships that are beneficial for good diabetes
      management.

PMID- 21895367
TI  - Executive control resources and frequency of fatty food consumption: findings
      from an age-stratified community sample.
AB  - OBJECTIVE: Fatty foods are regarded as highly appetitive, and self-control is
      often required to resist consumption. Executive control resources (ECRs) are
      potentially facilitative of self-control efforts, and therefore could predict
      success in the domain of dietary self-restraint. It is not currently known
      whether stronger ECRs facilitate resistance to fatty food consumption, and
      moreover, it is unknown whether such an effect would be stronger in some age
      groups than others. The purpose of the present study was to examine the
      association between ECRs and consumption of fatty foods among healthy community
      dwelling adults across the adult life span. METHODS: An age-stratified sample of
      individuals between 18 and 89 years of age attended two laboratory sessions.
      During the first session they completed two computer-administered tests of ECRs
      (Stroop and Go-NoGo) and a test of general cognitive function (Wechsler
      Abbreviated Scale of Intelligence); participants completed two consecutive 1-week
      recall measures to assess frequency of fatty and nonfatty food consumption.
      RESULTS: Regression analyses revealed that stronger ECRs were associated with
      lower frequency of fatty food consumption over the 2-week interval. This
      association was observed for both measures of ECR and a composite measure. The
      effect remained significant after adjustment for demographic variables (age,
      gender, socioeconomic status), general cognitive function, and body mass index.
      The observed effect of ECRs on fatty food consumption frequency was invariant
      across age group, and did not generalize to nonfatty food consumption.
      CONCLUSIONS: ECRs may be potentially important, though understudied, determinants
      of dietary behavior in adults across the life span.

PMID- 21895368
TI  - Patient-healthcare provider communication: perspectives of African American
      cancer patients.
AB  - OBJECTIVE: African Americans are often viewed as ineffective communicators during
      medical encounters. However, most previous studies have been conducted among
      noncancer populations and based on the perceptions of health care providers (HCP)
      and researchers. This study aimed to explore African American cancer patients'
      perspectives of HCPs' communication behaviors and how these communication
      patterns facilitate or hinder their cancer management and survivorship
      experiences. METHODS: This is a secondary data analysis of qualitative interviews
      with 28 African American cancer patients residing in the Southeastern U.S.
      Participants were purposefully selected to represent patients of both genders
      with varied sociodemographic characteristics. Grounded theory techniques of
      constant comparison were used to identify patterns of responses from the
      participants. RESULTS: Four major themes were identified about communication
      patterns between these cancer patients and their HCPs during diagnosis and
      treatment: (1) communication of cancer information; (2) communication of shared
      decision making; (3) communication of empathy and understanding; and (4)
      communication of respect. This study also described the effects of patient-HCP
      communication (e.g., satisfaction with oncology care, emotional distress, patient
      loyalty, treatment adherence, decisional regrets). CONCLUSIONS: African American
      cancer patients in this study perceived that HCPs demonstrated different levels
      of communication sensitivity and skills during cancer diagnosis and treatment.
      They also believed that HCPs' communication behaviors directly affected their
      survivorship experiences. Our findings help to gain knowledge of patient-HCP
      communication and to identify potential strategies for better communication
      between patients and HCPs among middle-aged and older African American cancer
      patients, which will ultimately promote culturally sensitive oncology care.

PMID- 21895369
TI  - Daily stress and cortisol patterns in parents of adult children with a serious
      mental illness.
AB  - OBJECTIVE: The goal of the current study was to examine whether parenting an
      adult child with a serious mental illness (SMI) has a physiological impact on
      parents. METHOD: Multiple samples of saliva were collected on 4 days from 61
      parents (mean age = 60.07 years, SD = 10.01) of individuals with a SMI (bipolar
      disorder, schizophrenia, and major depression; mean age = 32.46 years, SD =
      10.57) and a comparison group of 321 parents (mean age = 58.09 years, SD = 12.88)
      of individuals without a SMI (mean age = 32.36; SD = 13.87). Saliva samples were
      assayed for the hormone cortisol and group differences in diurnal cortisol
      patterns and their association with daily stress severity were explored. RESULTS:
      On days after elevated stress, a hypoactivation pattern of diurnal cortisol
      suggestive of chronic stress was evident for parents of individuals with a SMI.
      After more stressful days, cortisol levels increased less from waking to 30 min
      after waking and declined less from 30 min after waking to bedtime for parents of
      individuals with a SMI. CONCLUSIONS: The results of the current study add to a
      growing body of evidence that the long-term effects of parenting an adult with a
      disability has a biological impact on aging parents and support the need for
      family interventions across adulthood and into old age for parents of individuals
      with SMI.

PMID- 21895370
TI  - Understanding narrative effects: the impact of breast cancer survivor stories on
      message processing, attitudes, and beliefs among African American women.
AB  - OBJECTIVE: Examine the longitudinal effects of personal narratives about
      mammography and breast cancer compared with a traditional informational approach.
      METHODS: African American women (n = 489) ages 40 and older were recruited from
      low-income neighborhoods in St. Louis, Missouri, and randomized to watch a
      narrative video comprised of stories from African American breast cancer
      survivors or a content-equivalent informational video. Effects were measured
      immediately postexposure (T2) and at 3- (T3) and 6-month (T4) follow-up. T2
      measures of initial reaction included positive and negative affect, trust,
      identification, and engagement. T3 message-processing variables included arguing
      against the messages (counterarguing) and talking to family members about the
      information (cognitive rehearsal). T4 behavioral correlates included perceived
      breast cancer risk, cancer fear, cancer fatalism, perceived barriers to
      mammography, and recall of core messages. Structural equation modeling examined
      interrelations among constructs. RESULTS: Women who watched the narrative video
      (n = 244) compared to the informational video (n = 245) experienced more positive
      and negative affect, identified more with the message source, and were more
      engaged with the video. Narratives, negative affect, identification, and
      engagement influenced counterarguing, which, in turn, influenced perceived
      barriers and cancer fatalism. More engaged women talked with family members more,
      which increased message recall. Narratives also increased risk perceptions and
      fear via increased negative affect. CONCLUSIONS: Narratives produced stronger
      cognitive and affective responses immediately, which, in turn, influenced message
      processing and behavioral correlates. Narratives reduced counterarguing and
      increased cognitive rehearsal, which may increase acceptance and motivation to
      act on health information in populations most adversely affected by cancer
      disparities.

PMID- 21895371
TI  - Differential cognitive effects of cycling versus stretching/coordination training
      in middle-aged adults.
AB  - OBJECTIVE: Physical exercise has been linked to higher cognitive functioning and
      enhanced brain plasticity in aging humans. The most consistent positive effects
      have been reported for executive functions associated with frontal brain regions.
      In rodents, however, running has been shown to induce functional and structural
      changes in the hippocampus, a brain region known to be important for memory. It
      is still a matter of debate which cognitive functions are susceptible to exercise
      and whether an increase in cardiovascular fitness is beneficial for cognitive
      functioning. Moreover, little is known about the impact of exercise on cognition
      in middle-aged humans. METHOD: Sixty-eight sedentary men and women between 40 and
      56 years of age were randomly assigned to one of two training programs: aerobic
      endurance training (cycling) or nonendurance training (stretching/coordination).
      Both groups exercised twice a week for six months. Additionally, a sedentary
      control group was tested. At baseline and after six months, episodic memory,
      perceptual speed, executive functions, and spatial reasoning were assessed with
      standardized psychometric tests, and all participants underwent a cardiovascular
      fitness test. RESULTS: Significant improvements in memory were observed in both
      the cycling and the stretching/coordination group as compared with the sedentary
      control group. The improvement in episodic memory correlated positively with the
      increase in cardiovascular fitness. The stretching/coordination training
      particularly improved selective attention as compared with the cycling training.
      CONCLUSIONS: The results suggest that cardiovascular fitness has beneficial
      effects even in high-functioning middle-aged participants, but that these
      benefits are very specific to memory functions rather than a wider range of
      cognitive functions.

PMID- 21895372
TI  - Family poverty is associated with cytomegalovirus antibody titers in U.S.
      children.
AB  - OBJECTIVE: Early life environmental and psychological influences are thought to
      play an important role in the development of the immune system. Antibody response
      to latent herpesviruses has been used as an indirect measure of cell-mediated
      immune function but has seldom been applied to younger age groups. METHODS: We
      used data from the 1999-2004 National Health and Nutrition Examination Survey
      (NHANES) to test for an association between family poverty and continuous
      antibody response to cytomegalovirus in U.S. children aged 6-16 (N = 2,226) using
      ordinary least squares regression. RESULTS: Poverty was significantly associated
      with increased antibody levels among seropositive individuals. The association
      between income and antibody levels exhibited a threshold effect, with additional
      income beyond the poverty line not associated with increased antibody titers.
      This relationship was more robust among older compared with younger children.
      CONCLUSIONS: Early life social factors such as family poverty could have
      detrimental impacts on the developing immune system, with potentially important
      consequences for later life health outcomes. Exposure to socioeconomic stressors
      for longer periods during childhood may further enhance alterations in immune
      response to cytomegalovirus.

PMID- 21895373
TI  - Psychological distress in fibromyalgia patients: a role for catechol-O-methyl
      transferase Val158met polymorphism.
AB  - OBJECTIVE: Fibromyalgia (FM) has been related to biochemical alterations, central
      pain sensitization and psychological distress. Among genetic and environmental
      hypotheses, a role was suggested for catechol-O-methyl-transferase (COMT), a
      modulator in the metabolism of monoaminergic neurotransmitters. METHOD: This
      study compared the COMT Val158Met enzyme polymorphism (rs4680) of 198 FM patients
      to 99 pain-free controls. Psychological and functional aspects were assessed
      through investigating anxiety, depression, catastrophizing, perceived health, and
      functional status. RESULTS: The distribution of the COMT Val158Met polymorphism
      was similar in FM and controls. Out of 198 patients, 137 were able to stop
      medication before evaluation. In these patients, the COMT Val158Met genotype was
      associated with specific psychological profiles. The Met/Met subgroup scored
      systematically worse on all psychological and functional variables. All variables
      displayed a "genotype-trend effect" with the Met/Met and Val/Val subgroups at the
      two ends of the scores. Genotypes distribution in the 61 patients unable to stop
      medication was significantly different from that of patients able to stop
      medication and controls (p = .002 and p = .018, respectively) with an increase in
      the proportion of the Met/Met genotype associated to the lowest COMT activity.
      These results suggest a possible role of COMT Val158Met polymorphism in the
      psychological distress observed in FM. CONCLUSIONS: The association of COMT
      genotype with psychological distress may be of importance as identifying
      subgroups is a challenge in the diagnosis and treatment of fibromyalgia patients.
      This association may contribute to open new perspectives into the understanding
      of the pathophysiology of fibromyalgia and stress-related genes.

PMID- 21895374
TI  - Interdependent psychological quality of life in dyads adjusting to prostate
      cancer.
AB  - OBJECTIVE: Prostate cancer negatively influences quality of life (QOL) in
      survivors and the people with whom they are close. The purpose of this
      investigation was to assess the degree of dyadic interdependence in psychological
      QOL in dyads adjusting to prostate cancer and its treatment. METHOD: Participants
      were 70 prostate cancer survivors and their partners, most of whom were spouses.
      Assessments of psychological QOL (i.e., depression, anxiety, fatigue, and
      positive affect) were made at three points in time, each separated by 8 weeks.
      RESULTS: Survivors' prostate specific function was associated with both their own
      and their partners' psychological QOL. There was evidence of longitudinal dyadic
      interdependence for psychological QOL, particularly from partners to survivors
      between the T2 and T3 assessments. CONCLUSIONS: Prostate cancer survivors'
      psychological QOL is affected substantially by their partners' psychological QOL,
      consistent with theories of emotional contagion.

PMID- 21895375
TI  - Dynamic psychological and behavioral changes in the adoption and maintenance of
      exercise.
AB  - OBJECTIVE: Although health cognitions are regarded as key determinants for health
      behavior change, they are rarely studied from a dynamic perspective, evaluating
      the impact of changes in cognitions on changes in behavior. In the present study,
      we examine how changes in phase-specific and generic health cognitions influence
      first, the adoption of exercise and later, the maintenance of the newly acquired
      behavior. METHODS: Participants were middle-aged, Finnish adults participating in
      a lifestyle intervention to prevent Type 2 diabetes (N = 389). Health cognitions
      and exercise were measured at baseline (preintervention) and twice after a
      lifestyle intervention took place (at 3 months and after 1 year). RESULTS: The
      results show that both phase-specific and generic health cognitions changed
      during the intervention. However, these changes were most pronounced within those
      participants who started at a lower level to begin with. Most important, evidence
      for the dynamic interplay between changes in health cognitions and health
      behavior was observed: Phase-specific health cognitions facilitated the adoption
      as well as the maintenance of behavior changes. CONCLUSIONS: Thus, health
      cognitions are amenable to change, and these changes are adaptive in terms of
      initiating and maintaining health behavior change. This has implications both for
      practical intervention research, as well as for theory development.

PMID- 21895376
TI  - The SEA (Social cognition and Emotional Assessment): a clinical
      neuropsychological tool for early diagnosis of frontal variant of frontotemporal
      lobar degeneration.
AB  - OBJECTIVE: The frontal variant of frontotemporal degeneration (fvFTD) is
      characterized by a predominant behavioral syndrome, which is mostly attributable
      to an orbital-medial prefrontal dysfunction. The orbital and ventral medial
      prefrontal functions in humans are difficult to assess in clinical practice.
      Here, we propose a new tool, the SEA (Social cognition and Emotional Assessment),
      for use in evaluating the functions of the orbital and ventral-medial portions of
      the prefrontal cortex. METHOD: The SEA is composed of five subtests, each
      assessing a specific orbitofrontal-related function: a test of identification of
      facial emotions, a reversal/extinction task, a behavioral control task, a theory
      of mind test, and an apathy scale. The maximum score is 55. Three groups have
      been tested: 22 fvFTD patients, 22 patients with Alzheimer's disease (AD) or
      amnesic mild cognitive impairment (aMCI), and 30 healthy control subjects, all
      matched for age and educational level. RESULTS: FvFTD patients showed
      significantly lower performances in all subtests of the SEA. A cut-off score of
      39.4/55 was proposed to separate normal controls from fvFTD patients, with a
      maximum sensitivity and specificity of 100%. A very high specificity (88.5%) was
      obtained using the same cut-off with AD/aMCI patients and normal controls versus
      fvFTD patients. FvFTD patients' performance in the SEA did not correlate with any
      other neuropsychological scores, particularly the classical cognitive executive
      tests. CONCLUSIONS: The SEA is a new and useful tool for diagnosing fvFTD and,
      more generally, all of the diseases affecting the orbital and medial prefrontal
      functions.

PMID- 21895377
TI  - Deficits of contralesional awareness: a case study on what paper-and-pencil tests
      neglect.
AB  - OBJECTIVE: Attentional orienting and awareness for contralesional hemispace were
      studied longitudinally in a woman (GB) who suffered a right hemispheric stroke
      without any motor impairment and who presented normal performance on standard
      paper-and-pencil tests for neglect but manifested difficulties in everyday life.
      We aimed to test whether computer-based, dual-task paradigms were sufficiently
      sensitive to detect the presence of subclinical neglect in GB. METHOD: We
      assessed the spatial awareness of GB by means of cued-detection tasks, paper-and
      pencil tests, attentionally demanding dual tasks, and in several ecological
      settings after her discharge from the hospital. A group of right brain-damaged
      patients and an age-matched healthy participant were also tested with the dual
      tasks. RESULTS: Dramatic awareness deficits for the left contralesional hemispace
      emerged in GB only under dual-task conditions, both in computer-based and in
      ecological settings, as if her degree of contralesional space awareness
      impairment was closely dependent on the quantity of available attentional
      resources. Our dual-task paradigm was also effective in quantifying awareness
      improvements over time. The absence of motor impairments, uncommon for a
      postacute patient with severe albeit hidden neglect, allowed us to ascribe her
      everyday life impairments for contralesional hemispace to awareness deficits. The
      performance of the group of patients confirmed the detrimental effects of the
      dual tasks, whereas the performance of the healthy control we tested was not
      affected by dual-task manipulation. CONCLUSIONS: Our results confirm the well
      known lack of sensitivity of standard neuropsychological tests to detect
      subclinical forms of neglect, which, nonetheless, may result in negative
      consequences in everyday life. Computer-based, resource-demanding paradigms seem
      to be a promising solution to uncover subtle awareness deficits that can affect
      the everyday life of stroke patients.

PMID- 21895378
TI  - Age differences in memory for names: the effect of prelearned semantic
      associations.
AB  - Previous research has shown that people-especially older adults-have a special
      difficulty in learning the names of newly encountered people. This is potentially
      attributable to the lack of direct link in memory between a face and name. The
      present experiments investigated whether older and younger adults could use other
      semantic information about a person (i.e., a "mediator") to indirectly link a
      name to a face. In each of two experiments, older and younger adults prelearned
      associations between semantic information (character information or occupations)
      and names. They then attempted to learn links between faces and either the names
      or semantic information. In the "unmediated" condition, participants learned only
      one piece of information (either the name or the semantic information) about each
      face, whereas in the "mediated" condition, they learned both the to-be-tested
      information as well as the "mediator" (i.e., both the name and the other semantic
      information). Experiment 1 showed that, at a simple level, both age groups could
      use character information ("good" or "bad") to help recognize people's names,
      given their faces. Experiment 2 showed that knowing the occupation associated
      with a name helped both age groups to later recall the name associated with a
      given face.

PMID- 21895379
TI  - Let me guess how old you are: effects of age, gender, and facial expression on
      perceptions of age.
AB  - Perceptions of age influence how we evaluate, approach, and interact with other
      people. Based on a paramorphic human judgment model, the present study
      investigates possible determinants of accuracy and bias in age estimation across
      the adult life span. For this purpose, 154 young, middle-aged, and older
      participants of both genders estimated the age of 171 faces of young, middle
      aged, and older men and women, portrayed on a total of 2,052 photographs. Each
      face displayed either an angry, fearful, disgusted, happy, sad, or neutral
      expression (FACES database; Ebner, Riediger, & Lindenberger, 2010). We found that
      age estimation ability decreased with age. Older and young adults, however, were
      more accurate and less biased in estimating the age of members of their own as
      compared with those of the other age group. In contrast, no reliable own-gender
      advantage was observed. Generally, the age of older faces was more difficult to
      estimate than the age of younger faces. Furthermore, facial expressions had a
      substantial impact on accuracy and bias of age estimation. Relative to other
      facial expressions, the age of neutral faces was estimated most accurately, while
      the age of faces displaying happy expressions was most likely underestimated.
      Results are discussed in terms of methodological and practical implications for
      research on age estimation.

PMID- 21895380
TI  - The relation between anxiety disorder and experiential avoidance in inpatient
      adolescents.
AB  - The current study aimed to examine the relation between experiential avoidance
      and anxiety disorders, as well as the usefulness of the Avoidance and Fusion
      Questionnaire for Youth (AFQ-Y; Greco, Lambert, & Baer, 2008) in detecting
      anxiety disorder in a sample of adolescent inpatients. First, the relation
      between experiential avoidance and anxiety among inpatient adolescents was
      investigated from categorical and dimensional points of view, making use of self
      report and parent report, as well as clinical interview, while controlling for
      depression and externalizing problems. Second, we sought to establish the
      clinical utility value of the AFQ-Y by determining the sensitivity, specificity,
      and clinical cutoff score of this measure in predicting anxiety disorder. To this
      end, a sample of inpatient adolescents (N = 111) with a mean age of 16.14 (SD =
      1.39) years completed the AFQ-Y, alongside interview- and questionnaire-based
      measures of psychopathology. Results showed a significant relation between
      anxiety disorder and experiential avoidance, independent of depression. Receiver
      operating characteristics analysis revealed that the AFQ-Y has moderate accuracy
      (area under the curve = .815, SE = .047, p < .001) in discriminating adolescents
      with a diagnosis of any anxiety disorder (cutoff score 26.5; sensitivity = .74,
      specificity = .76). Given the comorbidity of anxiety and depression in this
      sample, this cutoff is not indicative of pure anxiety disorder but may be helpful
      in predicting those with emotional disorders in general.

PMID- 21895381
TI  - Social relationships and intraindividual variability in interpersonal behavior:
      correlates of interpersonal spin.
AB  - Personality constructs are typically conceptualized as central tendencies of the
      individual. We explore whether dynamic personality constructs that quantify the
      within-individual variability of behavior across situations and over time predict
      the closeness of social relationships. We focused on interpersonal spin, defined
      as the degree of dispersion in a person's interpersonal behaviors around the
      interpersonal circumplex across situations and over time. We predicted that
      individuals with high spin would have social relationships that are less close
      than individuals with low spin. In 3 studies with different measures of
      relationship closeness, we found that (a) higher spinners reported that a larger
      proportion of their contacts in their workplace social networks were distant
      (Study 1); (b) co-workers were less satisfied and less often engaged in pleasant
      activities with higher spinners (Study 2); and (c) co-workers avoided higher
      spinners with whom they were well acquainted (Study 3). Moderated mediation
      analyses in Study 3 revealed that co-workers avoided well-acquainted higher
      spinners because they felt more negative affect when interacting with these
      individuals. The findings suggest the potential of dynamic personality constructs
      for improving our understanding of the characteristics of individuals' social
      relationships.

PMID- 21895382
TI  - Restoration process of the need for autonomy: the early alarm stage.
AB  - Autonomy is described by self-determination theory as a basic psychological need,
      essential for individuals' well-being. While basic needs are generally thought to
      induce a restorative response when thwarted, evidence for such a process is
      lacking for autonomy. To date, most evidence indicates that autonomy deprivation
      leads to disaffection of this need in favor of other motives. A temporal model
      based on the general adaptation syndrome was adapted to reconcile this seeming
      contradiction. Specifically, it is hypothesized that an early alarm response
      aimed at restoring the satisfaction of the need for autonomy should precede the
      later relinquishment and compensation of this need that would result from a
      prolonged deprivation. Three studies provide support for this model by showing
      the existence of the immediate autonomy restorative response. Using a controlling
      situation to manipulate autonomy deprivation, the authors demonstrate in
      Experiments 1 and 2 that a controlling context leads to enhanced accessibility
      and an approach bias for autonomy-related stimuli. Experiment 3 indicates that
      the urge to restore autonomy can also affect personal judgment, leading
      individuals to make more independent judgments, exercising a nonreactive form of
      autonomy. Integration of this model within self-determination theory is
      discussed.

PMID- 21895383
TI  - A dynamic stimulus-driven model of signal detection.
AB  - Signal detection theory forms the core of many current models of cognition,
      including memory, choice, and categorization. However, the classic signal
      detection model presumes the a priori existence of fixed stimulus representations
      -usually Gaussian distributions--even when the observer has no experience with
      the task. Furthermore, the classic signal detection model requires the observer
      to place a response criterion along the axis of stimulus strength, and without
      theoretical elaboration, this criterion is fixed and independent of the
      observer's experience. We present a dynamic, adaptive model that addresses these
      2 long-standing issues. Our model describes how the stimulus representation can
      develop from a rough subjective prior and thereby explains changes in signal
      detection performance over time. The model structure also provides a basis for
      the signal detection decision that does not require the placement of a criterion
      along the axis of stimulus strength. We present simulations of the model to
      examine its behavior and several experiments that provide data to test the model.
      We also fit the model to recognition memory data and discuss the role that
      feedback plays in establishing stimulus representations.

PMID- 21895384
TI  - Recurrence in major depression: a conceptual analysis.
AB  - Theory and research on major depression have increasingly assumed a recurrent and
      chronic disease model. Yet not all people who become depressed suffer
      recurrences, suggesting that depression is also an acute, time-limited condition.
      However, few if any risk indicators are available to forecast which of the
      initially depressed will or will not recur. This prognostic impasse may be a
      result of problems in conceptualizing the nature of recurrence in depression. In
      the current paper we first provide a conceptual analysis of the assumptions and
      theoretical systems that presently structure thinking on recurrence. This
      analysis reveals key concerns that have distorted views about the long-term
      course of depression. Second, as a consequence of these theoretical problems we
      suggest that investigative attention has been biased toward recurrent forms of
      depression and away from acute, time-limited conditions. Third, an analysis of
      how these theoretical problems have influenced research practices reveals that an
      essential comparison group has been omitted from research on recurrence: people
      with a single lifetime episode of depression. We suggest that this startling
      omission may explain why so few predictors of recurrence have as yet been found.
      Finally, we examine the reasons for this oversight, document the validity of
      depression as an acute, time-limited disorder, and provide suggestions for future
      research with the goal of discovering early risk indicators for recurrent
      depression.

PMID- 21895385
TI  - Post-stop-signal slowing: strategies dominate reflexes and implicit learning.
AB  - Control adjustments are necessary to balance competing cognitive demands. One
      task that is well-suited to explore control adjustments is the stop-signal
      paradigm, in which subjects must balance initiation and inhibition. One common
      adjustment in the stop-signal paradigm is post-stop-signal slowing. Existing
      models of sequential adjustments in the stop-signal paradigm suggest that post
      stop-signal slowing may be based solely on the events of the previous trial,
      suggesting that post-stop-signal slowing is a reflexive byproduct of a stop
      signal. Alternatively, post-stop-signal slowing could be the result of implicit
      learning or strategic adjustment. The authors report three experiments that
      manipulated the probability of stop trial repetition and found that these
      contingencies eliminate, reverse, or greatly increase post-stop-signal slowing.
      When the contingency was not instructed or cued, modest adjustments of post-stop
      signal slowing occurred, suggesting implicit learning. When the contingency was
      cued, performance adjustments occurred on the next trial, suggesting that
      strategies dominated post-stop-signal slowing. These results show that post-stop
      signal slowing is not a reflexive byproduct of the stop signal. The large changes
      in strategy accompany large changes in task factors, suggesting that the modest
      post-stop-signal slowing usually observed may be a result of the relatively
      static task environment that does not encourage large strategic changes.

PMID- 21895386
TI  - Transfer of recalibration from audition to touch: modality independence as a
      special case of anatomical independence.
AB  - An important step in developing a theory of calibration is establishing what it
      is that participants become calibrated to as a result of feedback. Three
      experiments used a transfer of calibration paradigm to investigate this issue. In
      particular, these experiments investigated whether recalibration of perception of
      length transferred from audition to dynamic (i.e., kinesthetic) touch when
      objects were grasped at one end (Experiment 1), when objects were grasped at one
      end and when they were grasped at a different location (i.e., the middle)
      (Experiment 2), and when false (i.e., inflated) feedback was provided about
      object length (Experiment 3). In all three experiments, there was a transfer of
      recalibration of perception of length from audition to dynamic touch when
      feedback was provided on perception by audition. Such results suggest that
      calibration is not specific to a particular perceptual modality and are also
      consistent with previous research that perception of object length by audition
      and dynamic touch are each constrained by the object's mechanical properties.

PMID- 21895387
TI  - Immediate small number perception: evidence from a new numerical carry-over
      procedure.
AB  - Evidence is presented for the immediate apprehension of exact small quantities.
      Participants performed a quantification task (are the number of items greater or
      smaller than?), and carry-over effects were examined between numbers requiring
      the same response. Carry-over effects between small numbers were strongly
      affected by repeats of pattern and number identity relative to when displays were
      from the same response category but contained different numbers. Carry-over
      effects with large items were less sensitive to both pattern and number identity,
      even when the numbers in the small and large categories were matched for
      discriminability. The data suggest that small numbers are immediately apprehended
      through a direct subitization process distinct from pattern recognition and the
      apprehension of approximate number.

PMID- 21895388
TI  - A 2.5-D representation of the human hand.
AB  - Primary somatosensory maps in the brain represent the body as a discontinuous,
      fragmented set of two-dimensional (2-D) skin regions. We nevertheless experience
      our body as a coherent three-dimensional (3-D) volumetric object. The links
      between these different aspects of body representation, however, remain poorly
      understood. Perceiving the body's location in external space requires that
      immediate afferent signals from the periphery be combined with stored
      representations of body size and shape. At least for the back of the hand, this
      body representation is massively distorted, in a highly stereotyped manner. Here
      we test whether a common pattern of distortions applies to the entire hand as a 3
      D object, or whether each 2-D skin surface has its own characteristic pattern of
      distortion. Participants judged the location in external space of landmark points
      on the dorsal and palmar surfaces of the hand. By analyzing the internal
      configuration of judgments, we produced implicit maps of each skin surface.
      Qualitatively similar distortions were observed in both cases. The distortions
      were correlated across participants, suggesting that the two surfaces are bound
      into a common underlying representation. The magnitude of distortion, however,
      was substantially smaller on the palmar surface, suggesting that this binding is
      incomplete. The implicit representation of the human hand may be a hybrid,
      intermediate between a 2-D representation of individual skin surfaces and a 3-D
      representation of the hand as a volumetric object.

PMID- 21895389
TI  - Broken expectations: violation of expectancies, not novelty, captures auditory
      attention.
AB  - The role of memory in behavioral distraction by auditory attentional capture was
      investigated: We examined whether capture is a product of the novelty of the
      capturing event (i.e., the absence of a recent memory for the event) or its
      violation of learned expectancies on the basis of a memory for an event
      structure. Attentional capture-indicated by disruption of a focal visually
      presented serial recall task-was found when the voice conveying a concurrent
      irrelevant auditory sequence changed every 5 recall trials (from male to female
      or vice versa). There was no evidence of attentional capture when the irrelevant
      sequence was first encountered and hence novel; capture occurred only when an
      expectation for a particular voice had been learned and then violated.
      Furthermore, with the increasing predictability of (and hence expectancy for) the
      voice changes across the experimental session, the capture response diminished
      only to be reinstated when that session-wide expectation was itself violated by a
      break in the change-every-5-trials pattern. The results highlight the critical
      role of learned expectations, as opposed to novelty detection, in behavioral
      auditory attentional capture.

PMID- 21895390
TI  - How the measurement of memory processes can affect memory performance: the case
      of remember/know judgments.
AB  - Relatively little attention has been paid thus far in memory research to the
      effects of measurement instruments intended to assess memory processes on the
      constructs being measured. The current article investigates the influence of
      employing the popular remember/know (R/K) measurement procedure on memory
      performance itself. This measurement procedure was extensively used in the past
      to assess the respective contributions of 2 processes to memory judgments, one
      based on familiarity and the other on recollection. Two experiments using
      unrelated word pairs showed that the use of an R/K procedure can alter memory
      performance. Specifically, the R/K procedure improved associative memory among
      older but not younger adults compared to conditions in which participants were
      not asked to provide R/K judgments. Such an effect was not observed in item
      memory performance. Potential mechanisms mediating these differential memory
      measurement effects are outlined, and the measurement effects' implications for
      memory and cognitive research are discussed.

PMID- 21895391
TI  - The functional unit of Japanese word naming: evidence from masked priming.
AB  - Theories of language production generally describe the segment as the basic unit
      in phonological encoding (e.g., Dell, 1988; Levelt, Roelofs, & Meyer, 1999).
      However, there is also evidence that such a unit might be language specific.
      Chen, Chen, and Dell (2002), for instance, found no effect of single segments
      when using a preparation paradigm. To shed more light on the functional unit of
      phonological encoding in Japanese, a language often described as being mora
      based, we report the results of 4 experiments using word reading tasks and masked
      priming. Experiment 1 demonstrated using Japanese kana script that primes, which
      overlapped in the whole mora with target words, sped up word reading latencies
      but not when just the onset overlapped. Experiments 2 and 3 investigated a
      possible role of script by using combinations of romaji (Romanized Japanese) and
      hiragana; again, facilitation effects were found only when the whole mora and not
      the onset segment overlapped. Experiment 4 distinguished mora priming from
      syllable priming and revealed that the mora priming effects obtained in the first
      3 experiments are also obtained when a mora is part of a syllable. Again, no
      priming effect was found for single segments. Our findings suggest that the mora
      and not the segment (phoneme) is the basic functional phonological unit in
      Japanese language production planning.

PMID- 21895392
TI  - At the same time or apart in time? The role of presentation timing and retrieval
      dynamics in generalization.
AB  - Several bodies of research have found different results with regard to
      presentation timing, categorization, and generalization. Both presenting
      instances at the same time (simultaneous) and presenting instances apart in time
      (spacing) have been shown to facilitate generalization. In this study, we
      resolved these results by examining simultaneous, massed, and spaced
      presentations in 2-year-old children's (N = 144) immediate and long-term
      performance on a novel noun generalization task. Results revealed that, when
      tested immediately, children in the simultaneous condition outperformed children
      in all other conditions. However, when tested after 15 min, children in the
      spaced condition outperformed children in all other conditions. Results are
      discussed in terms of how retrieval dynamics during learning affect abstraction,
      retention, and generalization across time.

PMID- 21895393
TI  - Investigating cue competition in contextual cuing of visual search.
AB  - A fundamental principle of learning is that predictive cues or signals compete
      with each other to gain control over behavior. Associative and propositional
      reasoning theories of learning provide radically different accounts of cue
      competition. Propositional accounts predict that under conditions that do not
      afford or warrant the use of higher order reasoning processes, cue competition
      should not be observed. We tested this prediction in 2 contextual cuing
      experiments, using a visual search task in which patterns of distractor elements
      predict the location of a target object. Blocking designs were used in which 2
      sets of predictive distractors were trained in compound, with 1 set trained
      independently. There was no evidence of cue competition in either experiment. In
      fact, in Experiment 2, we found evidence for augmentation of learning. The
      findings are contrasted with the predictions of an error-driven associative model
      of contextual cuing (Brady & Chun, 2007).

PMID- 21895395
TI  - Further evidence for temporal decay in working memory: reply to Lewandowsky and
      Oberauer (2009).
AB  - The sources of forgetting in working memory (WM) are a matter of intense debate:
      Is there a time-related decay of memory traces, or is forgetting uniquely due to
      representation-based interference? In a previous study, we claimed to have
      provided evidence supporting the temporal decay hypothesis (S. Portrat, P.
      Barrouillet, & V. Camos, 2008). However, reanalyzing our data, S. Lewandowsky and
      K. Oberauer (2009) demonstrated that they do not provide compelling evidence for
      temporal decay and suggested a class of alternative models favoring a
      representation-based interference account. In this article, we develop from the
      most recent proposals made by Lewandowsky and Oberauer 2 of the most plausible
      extensions of these alternative models. We show that neither of these extensions
      can account for recent findings related to between-domain WM performance and that
      both lead to predictions that are contradicted by new empirical evidence.
      Finally, we show that recent studies that have been claimed to rule out the
      temporal decay hypothesis do not resist close scrutiny. We conclude that the time
      based resource-sharing model remains the most parsimonious way to account for
      forgetting and restoration of memory traces in WM.

PMID- 21895396
TI  - Phonological typicality influences sentence processing in predictive contexts:
      reply to Staub, Grant, Clifton, and Rayner (2009).
AB  - In 2 separate self-paced reading experiments, Farmer, Christiansen, and Monaghan
      (2006) found that the degree to which a word's phonology is typical of other
      words in its lexical category influences online processing of nouns and verbs in
      predictive contexts. Staub, Grant, Clifton, and Rayner (2009) failed to find an
      effect of phonological typicality when they combined stimuli from the separate
      experiments into a single experiment. We replicated Staub et al.'s experiment and
      found that the combination of stimulus sets affects the predictiveness of the
      syntactic context; this reduces the phonological typicality effect as the
      experiment proceeds, although the phonological typicality effect was still
      evident early in the experiment. Although an ambiguous context may diminish
      sensitivity to the probabilistic relationship between the sound of a word and its
      lexical category, phonological typicality does influence online sentence
      processing during normal reading when the syntactic context is predictive of the
      lexical category of upcoming words.

PMID- 21895397
TI  - Still no phonological typicality effect on word reading time (and no good
      explanation of one, either): a rejoinder to Farmer, Monaghan, Misyak, and
      Christiansen.
AB  - In this brief rejoinder, we respond to Farmer, Monaghan, Misyak, and Christiansen
      (2011). We argue that the data still do not support the claim that reading time
      is affected by the phonological typicality of a word for its part of speech. We
      also question Farmer et al.'s claim that interleaving syntactic structures in an
      experiment modifies grammatically based syntactic expectations.

PMID- 21895398
TI  - Ovarian cancer: origin and factors involved in carcinogenesis with potential use
      in diagnosis, treatment and prognosis of the disease.
AB  - Ovarian cancer representing the most lethal gynecologic malignancy escapes from
      the efforts to manage the disease. We reviewed the current state of the research
      considering three main concepts on origin of ovarian cancer including epithelial
      mesenchymal transition, secondary origin from Mullerian system and cancer stem
      cell hypothesis. Cytogenetic and molecular characteristics of ovarian cancer are
      focused particularly on microRNA expression studies revealing huge potential in
      recent years, although other transcriptomic, proteomic, epigenetic, epidemiologic
      and immunological factors are touched upon, too. Routine and investigated
      diagnostic and treatment methods are outlined and several factors revealed to be
      associated with prognosis of the disease. Despite the huge progress on
      elucidating factors involved in ovarian cancer carcinogenesis, still remains
      urgent need to improve both the diagnostics as well as the treatment.

PMID- 21895399
TI  - Molecular predictive factors of outcome of radiotherapy in cervical cancer.
AB  - Radical radiotherapy with concurrent cisplatin-based chemotherapy is an
      established treatment for cervical cancer patients with stage FIGO IIB and
      higher. The tumor control can be achieved in 40-80% of patients, the treatment is
      associated with the risk of late postiradiation complications in 10 - 15% of
      cases. Detection of the factors predictive for tumor control and late morbidity
      is a possible direction how to individualize radiotherapy dose and technique. The
      aim of our review is to summarize results of studies inquiring various molecular
      markers predicting tumor response to radiotherapy and a risk of late
      complications. A lot of candidate molecules were evaluated in histochemical
      studies: membrane receptors (EGFR, HER-2), cell cycle regulators (p53, p21),
      proliferative markers (Ki-67), hypoxia and angiogenetic factors (HIF, VEGF), HPV
      status, and others (COX-2), with promising results in some of them (HPV, HIF
      1alpha, Ku80, ATM polymorphism). Microarray studies identified decades of genes
      with different expression in radiosensitive/radioresistant cervical tumors and
      sets of genes are able to comletely separate responding and nonresponding tumors,
      but these sets differ across studies. Further well designed studies will be
      necessary to achieve results matured for use in clinical practice.

PMID- 21895400
TI  - Heterochromatin condensation in central and peripheral nuclear regions of
      maturing lymphocytes in the peripheral blood of patients suffering from B chronic
      lymphocytic leukemia - a cytochemical study.
AB  - The present study was undertaken to provide complementary information on
      heterochromatin condensation in central and peripheral nuclear regions during
      maturation of human leukemic lymphocytes using simple image processing and DNA
      image densitometry at the single cell level. Such approach indicated that the
      heterochromatin condensation in perinucleolar and extranucleolar "gene rich"
      central nucleolar regions preceded that in the "gene poor" nuclear periphery at
      the nuclear membrane. Thus, the maturation of lymphocytes was accompanied by a
      marked increase of the heterochromatin condensation at the nuclear membrane that
      reflected the maturity of these cells. In addition, in contrary to the nuclear
      size, no substantial differences of the heterochromatin condensation in central
      and peripheral nuclear regions were noted between untreated and treated patients
      with cytostatic therapy at the time of taking samples for the present study. On
      the other hand, the larger heterochromatin condensation in central nuclear
      regions occasionally persisted in small mature lymphocytes of all studied
      patients. Such phenomenon might represent the return to the cell cycle or a
      further type of maturation asynchrony that in leukemic cells is not exceptional.

PMID- 21895401
TI  - Metformin induces apoptosis of lung cancer cells through activating JNK/p38 MAPK
      pathway and GADD153.
AB  - There are epidemiological and experimental evidences that metformin, an insulin
      sensitizer agent widely used for diabetes treatment, has inhibitory effects on
      the growth of various human cancers. However, the underlying molecular mechanisms
      for its anti-neoplastic activity has not been yet clarified and the effect of
      metformin on human lung cancer remains unknown. In this study we revealed for the
      first time that metformin treatment led to increased apoptosis in human lung
      cancer cell lines A549 and NCI-H1299 and significantly inhibited the cells
      proliferation in a dose- and time-dependent manner, which was further
      demonstrated by the data obtained from A549 tumor xenografts in nude mice. We
      also found that metformin treatment can activate AMP-activated protein kinase,
      JNK/p38 MAPK signaling pathway and caspases, as well as upregulate the expression
      of growth arrest and DNA damage inducible gene 153 (GADD153). Either blockade of
      JNK/p38 MAPK pathway or knockdown of GADD153 gene abrogated the apoptosis
      inducing effect of metformin. Taken together, our data suggest that metformin
      inhibits the growth of lung cancer cells and induces apoptosis through activating
      JNK/p38 MAPK pathway and GADD153.

PMID- 21895402
TI  - Over-expression of protein kinase C isoforms (alpha, delta, theta and zeta) in
      squamous cervical cancer.
AB  - Protein kinase C was found to be significantly over-expressed in cancer samples
      compared to adjacent normal cervical tissues by proteomics in our previous study.
      The aim of this study was to examine protein kinase C expression and to analyze
      the expression patterns of protein kinase C isoforms in squamous cervical cancer
      at the protein levels and their associations with clinical and pathologic factors
      of squamous cervical cancer. First, Western blotting was used to examine protein
      kinase C expression in the specimens of tumors and matched adjacent normal
      tissues which were collected from 12 patients with squamous cervical cancer.
      Protein kinase C isoforms (alpha, delta, theta and zeta) expression were then
      detected by immunohistochemistry in other 43 cases of squamous cervical cancer
      tissues, 32 cases of corresponding adjacent normal cervical squamous epithelial
      tissue and 31 cases of cervical intraepithelial neoplasia. Western blot analysis
      revealed that protein kinase C expression was positive in squamous cervical
      cancer while it was not expressed in normal cervical tissues. On the other hand,
      immunohistochemical analysis suggested that, protein kinase C isoforms (alpha,
      delta, theta and zeta) expression was significantly higher in squamous cervical
      cancer compared to cervical intraepithelial neoplasia, as well as in cervical
      intraepithelial neoplasia compared with normal tissues, respectively.High levels
      of protein kinase C alpha expression were associated with cellular
      differentiation(P<0.05). Protein kinase C delta was significantly associated with
      tumor stage (P<0.05) and protein kinase C zeta was associated with lymphatic
      metastasis (P < 0.05). These findings indicate that protein kinase C isoforms
      expression in cervical lesions was associated with carcinogenesis and might play
      important roles throughout the process of cervical cancer development.

PMID- 21895403
TI  - Analysis of the serum levels of selected biological parameters in monoclonal
      gammopathy of undetermined significance and different stages of multiple myeloma.
AB  - The aim of the study was to analyze differences in the serum levels of 8 selected
      biological parameters between monoclonal gammopathy of undetermined significance
      (MGUS) and different stages of multiple myeloma (MM), potentially beneficial for
      distinguishing between the two conditions. The analyzed group of 131 subjects
      comprised 62 individuals with MGUS and 69 MM patients examined at the time of
      diagnosis. The serum levels were determined by a quantitative immunoradiometric
      assay (insulin-like growth factor 1, IGF-1) and quantitative sandwich enzyme
      immunoassay (osteopontin, OPN; endostatin, ES; macrophage inflammatory proteins
      1alpha/beta, MIP-1alpha/beta; angiogenin, ANG; and interleukin 17, IL-17). The
      analysis showed a statistically significant difference in serum concentrations
      between MGUS and the symptomatic form of MM using the Durie-Salmon (D-S) staging
      system only in the cases of OPN and stages II and III (0.001 and MM. More benefit
      may be expected from analyses using multiparametric immunophenotyping of plasma
      cells and molecular biology methods including gene expression analysis and
      proteomics.

PMID- 21895404
TI  - Feasibility of reducing the irradiation dose in regions of active neurogenesis
      for prophylactic cranial irradiation in patients with small-cell lung cancer.
AB  - Prophylactic cranial irradiation (PCI) is performed on patients with limited or
      extensive small-cell lung cancer to reduce incidence of brain metastases and
      prolong survival. PCI may induce neurocognitive impairment. Decreasing
      irradiation of neural stem cells (NSC) might reduce PCI-induced toxicity. We
      tested the feasibility of reducing irradiation doses to neural stem cell (NSC)
      regions while maintaining prescribed doses to the planned target volume (PTV).
      Irradiation plans utilizing intensity-modulated radiotherapy (IMRT), helical
      TomoTherapy, and RapidArc for 10 consecutive lung cancer patients were evaluated.
      The dose distribution, dose-volume histograms, and dose homogeneity indexes were
      analyzed. Planned and actual dose distributions were compared by dosimetric
      analysis. Both helical tomotherapy and LINAC-based IMRT reduced the radiation
      dose to the NSC regions by approximately 45% while maintaining the full dose to
      the rest of brain. Measured dose distributions matched the planned dose
      distributions.Protecting the regions of active neurogenesis is technically
      feasible. Whether reducing the dose by 35% to 45% is sufficient to reduce
      treatment toxicity, however, can only be addressed in a randomized study. Further
      reducing the dose within the NSC region might also significantly decrease the
      dosage to the PTV.

PMID- 21895405
TI  - Structure of flavonoids influences the degree inhibition of Benzo(a)pyrene -
      induced DNA damage and micronuclei in HepG2 cells.
AB  - Flavonoids are plant derivatives of flavone of which chemical structure is
      characterized by various degrees of hydroxylation and glycosidic substitution. In
      the present study we investigated the protective effect of two structurally
      different groups of flavonoids against-benzo[a]pyrene (B(a)P)-induced genotoxic
      effects on human hepatocellular carcinoma (HepG2) cells. The first group of
      flavonoids: fisetin, kaempferol, galangin, quercetin, and luteolin, hydroxylated
      at the 3',4'-position on the B ring, 3 - position of C ring and on the A ring was
      able to inhibit significantly B(a)P-induced genotoxic effects in a greater degree
      than the second group of flavonoids: chrysin, 7-hydroxyflavone, 7,8
      dihydroxyflavone and baicalein (hydroxylated on the A ring) which showed a
      statistically significant inhibition of genotoxicity mainly at higher
      concentrations (10 and 25 uM). The tenth flavonoid tested rutin, which contains
      hydroxyl group at the position 3 of C ring, substituted by the sugar rutinose,
      was not able to inhibit effectively genotoxic changes induced by B(a)P. Our
      results, obtained with help of micronucleus test and single cell gel
      electrophoresis (comet assay) suggest that inhibition of B(a)P-induced DNA
      lesions and micronuclei correlates with the structural arrangement and
      organization of the hydroxyl groups in the molecular structure of the flavonoids
      tested.

PMID- 21895406
TI  - Leukemic cells modulate induction of COX-2 in human stromal fibroblasts.
AB  - The interaction of cancer cells with surrounding normal tissue cells is of utmost
      importance for their survival and tumor progression. For these purposes the
      cancer cells exploit normal tissue responses associated with inflammation and
      tissue repair. In the immediate tumor microenvironment one of the early stromal
      markers is cyclooxygenase-2 (COX-2). In this study we evaluated the effect of
      leukemia cell lines on nemosis-induced COX-2 expression in stromal fibroblasts.
      We found that THP-1 cells were the most potent leukemic cells (IC50=746) to
      suppress COX-2 expression. The U-937 cell line exhibited similar suppressive
      potency (IC50=921), whereas the KG-1 cell line (IC50=3519) was the least potent
      to affect COX-2 expression in the stromal cells. Our study shows that human
      leukemic cells can actively participate in modulation of stromal inflammation via
      inhibition of COX-2 expression. In a co-culture model of leukemia cell lines and
      stromal fibroblasts, our data suggest that the tumor-stromal interactions are
      complexly regulated, and the straightforward association of COX-2 expression with
      tumor progression may require re-evaluation since some tumor cells, e.g. from
      hematologic malignancies, may differentially modulate inflammation and COX-2
      expression.

PMID- 21895407
TI  - Non-nuclear activation of signal transducer and activator of transcription 3 by
      17beta- estradiol in endometrial cancer cells.
AB  - Why estrogen hyperstimulation can lead to endometrial carcinogenesis has not been
      fully clear yet. Non-nuclear action of estrogen has arised much attention of many
      experts. Signal transducer and activator of transcription 3 is a very important
      signal molecule, which plays vital role in endometrial canver. The present study
      is oriented to the problem whether estrogen can activate STAT3 by non-nuclear
      action in endometrial cancer cells. So, the levels of phosphorylated STAT3 (P
      STAT3) and total STAT3 were examined by western blot in endometrial cancer cells
      including Ishikawa with rich-expressed estrogen receptor (ER) and HEC-1A with
      poor-expressed ER after stimulation with 1MUM estradiol (E2) at different time
      points and at varied doses of E2 for optimal time. Inhibitory role of AG490 on
      activation of STAT3 induced by E2 was also tested. P-STAT3/STAT3 was used as a
      measure of activation of STAT3. We found that maximum P-STAT3/STAT3 took place at
      15 min in both Ishikawa cells and HEC-1A cells. The activation of STAT3 elicited
      gradually with increasing doses of E2. AG490 stopped the activating STAT3 in the
      same dose-dependent manner in both endometrial cancer cells. The results
      demonstrate that E2 is able to activate STAT3 in both Ishikawa with rich
      expressed ER and HEC-1A with poor-expressed ER endometrial cancer cells by non
      nuclear action, which provides the preliminary laboratory basis for the
      probability of endometrial adenocarcinoma treatment with blockage of STAT3
      signaling, especially for ER-poor endometrial adenocarcinoma.

PMID- 21895408
TI  - Plasmid-based STAT3-siRNA efficiently inhibits breast tumor growth and metastasis
      in mice.
AB  - Signal transducer and activator of transcription 3 (STAT3) plays an important
      role in the tumor formation and metastasis. In this study, short hairpin RNA
      targeting STAT3 was cloned into pGenesil-2 plasmid vector and the effects of
      STAT3 silencing in 4T1 breast cancer cells were analyzed both in vitro and in
      vivo. Forty-eight hours after transfecting with pSi-STAT3, the expression level
      of STAT3, the upstream regulator and downstream targets were measured using
      Western blot. Moreover, the effects of pSi-STAT3 on migration and invasion in 4T1
      cells were tested using wound-healing and tube formation assay. Furthermore, 4T1
      subcutaneous mice model was used to evaluate the effects of pSi-STAT3 on tumor
      growth and metastasis. Proliferation, apoptosis, angiogenesis in tumor tissues
      and lung metastases were measured by PCNA, TUNEL, and CD31 immunostaining,
      respectively. Our results indicated that siRNA targeting STAT3 could
      significantly silence STAT3 expression in 4T1 breast cancer cells and result in
      inhibition of 4T1 breast cells migration and HUVECs tube formation. In vivo, pSi
      STAT3 delayed tumor growth (pknockdown of STAT3 by plasmid-based siRNA might be a
      potential therapy against breast cancer.

PMID- 21895409
TI  - Use of direct sequencing for detection of mutations in the BCR-ABL kinase domain
      in Slovak patients with chronic myeloid leukemia.
AB  - The presence of BCR-ABL oncogene mutations in patients with chronic myeloid
      leukemia (CML) may be responsible for the failure of tyrosine kinase inhibitor
      (TKI) treatment. The aim of the study was to evaluate the frequency of BCR-ABL
      gene mutations in patients with CML treated with tyrosine kinase inhibitors. Our
      lab received 64 samples (34 women, 30 men) from patients with CML who failed or
      had suboptimal response to TKI treatment. The mutation analysis was performed in
      61 patients with CML, 3 patients could not be tested because of inadequate RNA
      quality. An 866 base pair fragment containing the ABL kinase domain was amplified
      in a seminested RT (reverse transcriptase)-PCR and then sequenced using Applied
      Biosystems BigDye Terminator chemistry with two pairs of primers. We analyzed 61
      patients with CML, 11 mutations were detected in 13 (21%) patients and SNP
      (single nucleotide polymorphism) in 6 patients (10%). In addition to 9 point
      mutations (G250E / F317L, F359V, L387M, Y253H, M388L, M244V, T315I, D276G), 35 bp
      insertion between exons 8 and 9 and deletion exon 7 were detected. Our results
      demonstrate that direct sequencing is suitable for routine clinical monitoring
      patients with CML and may be useful for optimizing therapy.

PMID- 21895410
TI  - Prognostic significance of morphological assessment of plasma cells in multiple
      myeloma.
AB  - Multiple myeloma (MM) is a hematological malignancy caused by clonal
      proliferation of malignant plasma cells (PC). The aim of the work is to determine
      prognostic significance of morphological subtypes of PC in relation to overall
      treatment response, long-term survival and other conventional prognostic
      parameters. One hundred and thirty-nine newly diagnosed MM patients who underwent
      autologous transplantation in clinical trials conducted in one center were
      included. Percentual representation of subtypes of plasma cells in bone marrow
      was measured based on progressive analysis of nucleolus, nuclear chromatin and
      ratio of nuclei to the volume of cytoplasm (N/C ratio) creating 8 subtypes P000
      P111 and four subclassifications of cells. Mature plasma cells (P000, P001) were
      found in 42.4% of patients; proplasmocytes I (P010, P011, P100) in 38.1% of
      patients, and proplasmocytes II (P101, P110) in 19.4% of patients. Patients who
      reached treatment response after autologous transplantation had statistically
      significant lower frequency of mature plasma cells than patients with no
      treatment response (median 24.0% vs. 36.0 %; p=0.032). Patients with mature
      plasma cells of subtype P000 an patients with value P000 >= 37% (median 46.8
      months vs. 77.8 months; p = 0.020). Patients with proplasmocytes II subtype P110
      rings valuable prognostic information and correlation with other prognostic
      factors as well as total treatment response and survival in MM patients who
      underwent autologous transplantation.

PMID- 21895413
TI  - Youngia denticulata protects against oxidative damage induced by tert
      butylhydroperoxide in HepG2 cells.
AB  - Improvement of liver function is one of the most popular commercial health claims
      of functional foods in Asian countries, including Korea. After examining the
      potential of several traditional Korean wild vegetables for enhancing liver
      function, we found that Youngia denticulata Kitam. has strong hepatoprotective
      effects against oxidative stress induced by tert-butylhydroperoxide (t-BHP). We
      are the first to report that the extract and ethyl acetate fractions of Y.
      denticulata have radical scavenging activities and inhibit oxidative stress
      induced cell death and DNA damage in HepG2 cells. The extract and ethyl acetate
      fractions significantly decreased cellular reactive oxygen species production and
      apoptosis induced by t-BHP in HepG2 cells. In addition, they prevented the
      depletion of cellular glutathione, which is an important defense molecule against
      oxidizing xenobiotics. Chlorogenic acid and 3,5-dicaffeoylquinic acid were found
      to be major active components responsible for the activity of Y. denticulata and
      could serve as marker compounds for standardization. These data suggest that Y.
      denticulata could be promoted as a potential antioxidative functional food
      candidate, particularly for hepatoprotection against oxidative stress.

PMID- 21895414
TI  - Alcohol-fermented soybean increases the expression of receptor-interacting
      protein 2 and IkappaB kinase beta in mouse peritoneal macrophages.
AB  - Soybean is a useful component of traditional Korean medicine with well-documented
      health-promoting effects. We investigated the effects of alcohol-fermented
      soybean (AFS) on immune function. When AFS treatment was used in combination with
      recombinant interferon-gamma (rIFN-gamma), there was a marked cooperative
      induction of nitric oxide (NO) and tumor necrosis factor (TNF)-alpha production
      in mouse peritoneal macrophages. AFS increased the expression of inducible NO
      synthase mRNA and protein in rIFN-gamma-primed macrophages. Treating macrophages
      with pyrrolidine dithiocarbamate, an inhibitor of nuclear factor-kappaB (NF
      kappaB), decreased the synergistic effects of AFS. In addition, AFS in
      combination with rIFN-gamma increased the phosphorylation of p38 and c-Jun N
      terminal kinase (JNK) but not extracellular signal-regulated kinase. However, AFS
      had no effect on phosphorylation of mitogen-activated protein kinases by itself.
      The p38 inhibitor SB203580 or the JNK inhibitor SP600125 inhibited the AFS
      induced NO and TNF-alpha production. When AFS was used in combination with rIFN
      gamma, there was a co-operative activation of NF-kappaB and receptor-interacting
      protein 2 (Rip2)/IkappaB kinase (IKK)-beta. Our results indicate that AFS
      increases the production of NO and TNF-alpha through the activation of Rip2/IKK
      beta in rIFN-gamma-primed macrophages.

PMID- 21895415
TI  - Ginsenoside Rb1 inhibits cell activation and liver fibrosis in rat hepatic
      stellate cells.
AB  - Chronic hepatitis/cirrhosis is the eighth leading cause of death in Taiwan.
      Excess accumulated extracellular matrix produced by activated hepatic stellate
      cells (HSCs) is the major cause of liver fibrosis. Ginsenoside Rb1, the most
      active compound purified from ginseng, has been considered to be
      hepatoprotective. This study investigated the effects of ginsenoside Rb1 (98.8%
      purity) on activation, proliferation, and profibrotic factors in rat HSC-T6 cells
      under H2O2 oxidative stress. Rat HSC-T6 cells were activated by 10 nM H2O2 and
      then incubated with different concentrations of ginsenoside Rb1 (5, 10, 20, 40,
      and 80 MUg/mL) for 24 hours. Medium containing 0.08% dimethyl sulfoxide or 5 mM N
      acetyl-l-cysteine was used as a negative or positive control, respectively. The
      results showed that ginsenoside Rb1 at 5-40 MUg/mL significantly reduced alpha
      smooth muscle actin levels and at 5-80 MUg/mL inhibited cell proliferation in HSC
      T6 cells after induction with H2O2 (P<.05). Collagen secreted by HSC-T6 cells was
      decreased by ginsenoside Rb1 at 5-80 MUg/mL (P<.05). Protein expression of
      transforming growth factor-beta1 (TGF-beta1), matrix metalloproteinase (MMP)-2,
      and tissue inhibitor of metalloproteinase (TIMP)-1 was suppressed by ginsenoside
      Rb1 at 10-80 MUg/mL (P<.05). In addition, mRNA expression of type I and III
      collagen, TGF-beta1, and TIMP-1 was inhibited by ginsenoside Rb1 (10 and 80
      MUg/mL) (P<.05). Therefore, ginsenoside Rb1 exerted an antifibrotic effect on
      HSCs by inhibiting activation, proliferation, and expression of collagen, TGF
      beta1, MMP-2, and TIMP-1.

PMID- 21895416
TI  - Genotypic heterogeneity and molecular basis of 5-flucytosine resistance among
      Candida dubliniensis isolates recovered from clinical specimens in Kuwait.
AB  - There is a paucity of information about genotypic heterogeneity among Candida
      dubliniensis isolates recovered from different geographic regions. This study
      explored genotypic heterogeneity among 103 C. dubliniensis strains obtained over
      a six-year period from clinical specimens in Kuwait. Genotype assignment was
      based on amplification with genotype-specific primers and sequencing of rDNA.
      Susceptibility to 5-flucytosine was determined by means of the Etest. DNA
      sequencing of cytosine deaminase was performed to determine the molecular basis
      of resistance to 5-flucytosine. DNA sequencing of rDNA identified seven different
      genotypes, i.e., 68 (66%) isolates were found to belong to genotype 1, 25 to
      genotype 4, six to genotype 5 and one each to genotypes 6-9. Strains of genotype
      2 or genotype 3 were not detected. All isolates of genotype 4 but none of other
      genotypes were resistant to 5-flucytosine and the resistant strains all contained
      S29L mutation. Isolates of all other genotypes contained wild-type codon 29 in
      cytosine deaminase. A simple, PCR-RFLP-based method has been developed to
      facilitate rapid detection of S29L mutation in cytosine deaminase. A noteworthy
      observation of our study is the identification of five new genotypes of C.
      dubliniensis isolates, recovered from oral/respiratory specimens from patients of
      Middle Eastern origin. Furthermore, all 5-flucytosine resistant C. dubliniensis
      isolates in Kuwait belonged to genotype 4 only.

PMID- 21895417
TI  - Endoscopic transnasal cauterization of the anterior ethmoidal artery.
AB  - CONCLUSIONS: In our experience, the technique described can be applied
      independently according to the specific patient's anatomy and disease, allowing
      simple, easy, and safe identification of the anterior ethmoidal artery (AEA).
      OBJECTIVES: The aim of this study was to provide the anatomic rationale for
      endoscopic cauterization of the AEA and to present our surgical approach to AEA
      in the treatment of severe nasal bleeding. METHODS: A retrospective study
      reviewed 300 endoscopic transnasal AEA cauterizations, over a 20-year period from
      1991 to July 2010, at the Instituto Felippu, Sao Paolo, Brazil. All surgeries
      were carried out under general anesthesia and with the help of a rigid 30 degrees
      endoscope. RESULTS: The AEA was identified in all the patients treated. In 299
      patients we found the AEA located at the level of the horizontal portion of the
      frontal bone into the anterior ethmoidal canal; in 88 (29.4%) of these patients
      the canal bone was partially open and in 211 (70.6%) it was completely closed. In
      only one patient, we found a dehiscent AEA. No patients presented short-term
      failure and/or long-term failure.

PMID- 21895418
TI  - Sensory acceptability and factors predicting the consumption of grain amaranth in
      Kenya.
AB  - This study investigated the effect of adding grain amaranth flour on sensory
      acceptability of maize porridge in Kenya. Factors influencing the intention of
      mothers to feed their children on grain amaranth were identified. A significant
      difference between the various porridge ratios (50:50, 70:30, and 100:0
      amaranth:maize) either in unfermented or fermented form could be detected.
      Preference for the unfermented amaranth enriched maize porridge was observed.
      Intention significantly correlated and predicted grain amaranth consumption (p <
      .001). Knowledge and health value significantly predicted health behavior
      identity. Interaction between barriers and intention negatively influenced
      behavior. Findings suggest that unfermented amaranth enriched maize porridge is
      acceptable. Unfermented porridge with 70% amaranth can be considered for use in a
      program aimed at increasing dietary iron intake among children. Increasing
      awareness about micronutrient deficiencies and nutritional benefits of grain
      amaranth could enhance its consumption.

PMID- 21895419
TI  - The potential of local farming on the Navajo Nation to improve fruit and
      vegetable intake: barriers and opportunities.
AB  - American Indian populations have low produce intake compared to other ethnic
      groups and higher rates of diet-related chronic diseases. Programs linking
      farmers to their community (Farm-to-Table) are an innovative way to alter the
      food environment. We interviewed Navajo farmers (n = 20), storeowners (n = 7),
      and non-governmental organization representatives (n = 4) to better understand
      local farming practices and the potential of a Farm-to-Table program to increase
      produce intake. Barriers to participation in a Farm-to-Table program included
      lack of water, insufficient help, and exotic species. Participants expressed
      concern about high obesity rates and voiced support for a Farm-to-Table program
      if barriers could be adequately addressed.

PMID- 21895420
TI  - Interstate migration and changing food preferences in India.
AB  - India is a diversified country. Just as the geography, religion, and culture of
      India are diverse, so are Indians' food habits. Even so, regional heterogeneity
      in food consumption exists across states. But it may be hypothesized that
      regional heterogeneity in food consumption across states has been declining. This
      hypothesis is based on the fact that interstate migration has been growing since
      1991. The present study tested whether or not regional heterogeneity in food
      consumption has been declining over the years 1993-1994, 1999-2000, and 2004
      2005. The authors show that regional heterogeneity declined over these periods
      and that both rural and urban consumers shifted their preference from cereals to
      non-cereals. However, the article also provides some evidence that regional
      disparities remain in India. Implications of this shift in consumption are
      discussed.

PMID- 21895421
TI  - Horticultural and gathering practices complement each other: a case study in a
      rural population of Northwestern Patagonia.
AB  - We investigated gathering and cultivating practices and how they complement each
      other in a rural population of Northwestern Patagonia. We analyzed plant
      diversity, species similarity, biogeographic origin, and plant use by means of
      semi-structured interviews and field visits. Pichi Leufu inhabitants used 173
      species: 138 cultivated plants, mainly for edible purposes, and 45 wild species
      principally for medicinal use. Most cultivated species were exotic (91.3%),
      whereas gathered plants were both native and exotic. While locals maintained
      vegetable gardens, the adoption of greenhouses improved conditions for certain
      crops. The integration of novel practices with ancestral knowledge suggests
      resilient processes in this community, probably reflected in the dynamics of
      current horticultural and gathering practices, which complement each other.

PMID- 21895422
TI  - Antioxidant and type 2 diabetes related functional properties of phytic acid
      extract from Kenyan local food ingredients: effects of traditional processing
      methods.
AB  - Emerging scientific evidences reveal that phytic acid has several positive
      effects on human health. The antioxidant and type 2 diabetes related enzyme
      inhibition properties of phytic acid extract prepared from raw and traditionally
      processed local grains and vegetables collected from Kenya were evaluated. Phytic
      acid content of raw grains and vegetables ranged between 2.81-3.01 and 0.29-3.23
      g/100 g DM, respectively. The phytic acid extract from raw samples revealed 59%
      89% of DPPH radical scavenging capacity, 27-3,526 mmol Fe(II)/g extract of
      reducing power, 20%-72% of alpha-amylase inhibition activity and 8%-91% of alpha
      glucosidase inhibition activity. Cooking and roasting improved the antioxidant
      and health relevant functionality of phytic acid extracts obtained from Kenyan
      local vegetables and grains, respectively.

PMID- 21895423
TI  - Self-regulatory skills usage strengthens the relations of self-efficacy for
      improved eating, exercise, and weight in the severely obese: toward an
      explanatory model.
AB  - Lack of success with behavioral weight-management treatments indicates a need for
      a better understanding of modifiable psychological correlates. Adults with class
      2 and 3 obesity (N = 183; Mean(BMI) = 42.0 kg/m(2)) volunteered for a 26-week
      nutrition and exercise treatment, based on social cognitive theory, that focused
      on self-efficacy and self-regulation applied to increasing cardiovascular
      exercise and fruit and vegetable consumption. Improved self-efficacy for
      controlled eating significantly predicted increased fruit and vegetable
      consumption (R(2) = .15). Improved self-efficacy for exercise significantly
      predicted increased exercise (R(2) = .46). When changes in self-regulatory skill
      usage were stepped into the 2 previous equations, the variances accounted for
      significantly increased. Increases in fruit and vegetable consumption and
      exercise significantly predicted weight loss (R(2) = .38). Findings suggest that
      behavioral theory should guide research on weight-loss treatment, and a focus on
      self-efficacy and self-regulatory skills applied to specific nutrition and
      exercise behaviors is warranted.

PMID- 21895424
TI  - Smoking, depression, and gender in low-income African Americans with HIV/AIDS.
AB  - Individuals with HIV/AIDS have disproportionately high depression and smoking
      prevalence rates. Smokers with HIV/AIDS are more susceptible to opportunistic
      infections, smoking-related illnesses, and mortality. African Americans (AAs)
      comprise nearly half of newly diagnosed HIV+ cases. We examined the relationship
      among smoking, depression, and gender in un- or under-insured AA patients (N =
      289) at an urban community HIV/AIDS clinic in the southeastern US. Approximately
      33% met criteria for a depressive disorder and 37% endorsed current smoking
      status. Men were more likely than women to be current smokers and depressed
      participants were more likely to smoke than non-depressed participants. Women had
      significantly higher rates of depression compared to men. Both depression and
      male gender independently predicted current smoking status. Depression and
      smoking are likely to co-occur in HIV/AIDS patients; however, standard smoking
      cessation interventions often exclude smokers with comorbid psychiatric and/or
      medical illnesses. Interventions addressing these comorbidities are warranted.

PMID- 21895425
TI  - Cynical hostility, anger expression style, and acute myocardial infarction in
      middle-aged Japanese men.
AB  - Studies using American and European populations have demonstrated that high
      levels of anger/ hostility are predictive of coronary heart disease (CHD)
      mortality. However, Japanese studies did not show consistent relationship between
      anger/hostility and CHD. This study examines the association of cynical hostility
      and anger expression style with acute myocardial infarction (AMI) in middle-aged
      Japanese men through a case-control study. The patients with acute myocardial
      infarction (N = 96, mean age = 50.8 years) and the healthy participants in a
      health check-up program (N = 77, mean age = 50.3 years) were studied. Both groups
      completed the Cynicism Questionnaire (CQ) and the State-Trait Anger Expression
      Inventory (STAXI). The patients exhibited higher scores on CQ than the healthy
      controls. Logistic regression analyses controlling for biological risk factors
      revealed that the CQ score was associated with increased risk of AMI (OR = 1.11
      [95% CI 1.00-1.22]). In addition, the score of Anger-control, a subscale of
      STAXI, was associated with decreased risk of AMI (OR = 0.75 [95% CI 0.62-0.92]).
      These results indicated that higher levels of cynical hostility increased the
      risk of AMI and that anger-control strategies could have some benefit in reducing
      the risk of AMI in middle-aged Japanese men.

PMID- 21895426
TI  - Social cognitive variables as correlates of physical activity in persons with
      multiple sclerosis: findings from a longitudinal, observational study.
AB  - There is a lack of data regarding the associations among changes in social
      cognitive variables and physical activity over time in persons with multiple
      sclerosis (MS). To that end, the current study adopted a panel design and
      analysis for examining hypothesized relationships among changes in social
      cognitive variables and physical activity over time in persons with MS, and this
      is necessary for designing effective behavioral interventions. On two occasions
      separated by an 18-month period, persons (N = 218) with relapsing-remitting MS
      (RRMS), who were initially recruited by telephone for a cross-sectional study,
      completed a battery of questionnaires that assessed social cognitive variables
      and physical activity. Those study materials were delivered and returned via the
      United State Postal Service. The 18-month changes in self-efficacy (path
      coefficient = .25, p < .01) and goal setting (path coefficient = .26, p < .01)
      had direct effects on residual change in physical activity. The change in self
      efficacy further had an indirect effect on residual change in physical activity
      that was accounted for by change in goal setting (path coefficient = .05, p <
      .05). This longitudinal study suggests that self-efficacy and goal setting
      represent plausible targets for changing physical activity behavior in persons
      with RRMS.

PMID- 21895427
TI  - Fear of progression in partners of chronically ill patients.
AB  - Fear of progression (FoP) is one of the most prevalent symptoms in cancer
      patients. This chronic disease does not only have a profound impact on patients,
      but also on their spouses. The aim of this study was to evaluate the psychometric
      properties of a spouse FoP questionnaire (FoP-Q-SF/P) in 227 partners of
      chronically ill patients (breast cancer, prostate cancer, and diabetes mellitus)
      in Germany. Estimates of reliability were high (alpha = 0.88). The original one
      factor structure of the FoP-Q-SF for patients was replicated. We used the
      Hamilton Anxiety and Depression Scale, Impact of Event Scale-revised, Short Form
      8 Health Survey, Quality of Marriage Index, Partnership Questionnaire, and Dyadic
      Coping Inventory to validate the FoP-Q-SF/P. Significant positive correlations
      were found for anxiety, hyperarousal and intrusion (r > .61) as well as for
      depression and avoidance (r > .51). Partners of patients with cancer reported
      significantly higher levels of FoP than did partners of patients with diabetes
      mellitus. The FoP-Q-SF/P is a reliable and valid instrument that can be
      recommended for further use in research and clinical care.

PMID- 21895428
TI  - Serum levels of interleukin-6 and interleukin-10 in relation to depression scores
      in patients with cardiovascular risk factors.
AB  - It is currently unknown whether elevated cytokine levels in depression are
      confined to any specific subgroup of depressive patients. In this study, medical
      out-patients presenting with cardiovascular risk factors (N = 356) were assessed
      for both cognitive-affective and physical symptoms of depression using the
      Hospital Anxiety and Depression Scale (HADS) and the Maastricht questionnaire
      (MQ), respectively. In study participants assigned to the highest (>=21) and
      lowest (<=5) quartile for the MQ score, serum levels of cytokines were measured.
      We found highly significant associations between cognitive-affective symptoms of
      depression and elevated serum levels of interleukin-6 (IL-6; rho = .231; p =
      .002) and interleukin-10 (IL-10; rho = .370; p < .001), respectively. In multiple
      regression models elevated IL-10 serum concentration was independently related to
      cognitive-affective symptoms of depression (rho = .165; p = .002). When all
      cytokines were included in one model, elevated IL-10 serum concentrations
      remained a significant predictor for depressive mood (rho = .157; p = .009). In
      patients with cardiovascular risk factors and extreme scores for vital
      exhaustion, elevated serum IL-6 and even more IL-10 concentrations are linked to
      the presence of depressive mood. Future studies will have to test whether the so
      far unreported association of IL-10 with depressive mood represents a causal
      pathway involved in the pathogenesis or in the prognostic effect of depressive
      mood in cardiac patients.

PMID- 21895429
TI  - Editor's introduction. Special double issue: grief, loss, and bereavement.

PMID- 21895430
TI  - Death part three (it never ends).

PMID- 21895431
TI  - Bereavement therapy.

PMID- 21895432
TI  - Helping older widows rebuild their lives.
AB  - Hospice support groups can help older widows rebuild their lives after losing
      their husbands. To establish new-normal patterns for their lives, grieving widows
      need to address these questions: (a) What parts do you want your family and
      friends to play in your new-normal life?; (b) How do you want to spend your time,
      now that spending time with your husband is no longer possible?; and (c) How can
      your inner resources help you develop a frame of mind where you find peace and
      joy?

PMID- 21895433
TI  - An assessment of hospice bereavement programs for Hispanics.
AB  - Hispanics are the fastest growing minority group in the United States, numbering
      over 42 million and comprising 15% of the total population (U.S. Census Bureau,
      2008 ). Hispanics are a heterogeneous group that experience disparities in
      accessing health care, including at the end of life. Specific gaps can be
      identified in the care of bereaved Hispanic individuals and families. This
      exploratory study examined bereavement services available and perceived needs for
      Hispanics in Florida. Hospice bereavement coordinators indicated that limited
      services were available specifically for Spanish-speakers and that language and
      cultural barriers were challenges when communicating, offering, and delivering
      bereavement services to Hispanics. Implications for social workers include the
      need to increase access to and evaluate the effectiveness of bereavement services
      for Hispanics.

PMID- 21895434
TI  - Support after stillbirth and its effect on parental grief over time.
AB  - In this study the authors describe parents' experiences of support over a 2-year
      period after a stillbirth and its effect on parental grief. Data was collected by
      questionnaire from 33 mothers and 22 fathers at 3 months, 1 year, and 2 years
      after a stillbirth. Midwives, physicians, counselors, and priests--at the
      hospital where the stillbirth occurred--are those on the front line providing
      professional support. The support from family and friends was seen to be
      important 2 years after the stillbirth. The need for professional support after
      stillbirth can differ, depending on the support provided by family, friends, and
      social networks. They may not fully realize the value of their support and how to
      be supportive. Printed educational materials given to individuals in the social
      network or family might therefore be helpful.

PMID- 21895435
TI  - A qualitative study of advice from bereaved parents and siblings.
AB  - Despite a growing bereavement literature, relatively little is known about what
      families find helpful after a child's death and how best to assist them during
      the grieving process. In this qualitative study, the authors explored advice from
      40 families (65 parents, 39 siblings) of children who died from cancer 6-19
      months earlier. Content analysis emphasized the individual nature of grief and
      revealed advice that fit into three temporal categories: before the death, soon
      after, and long-term. Findings are discussed in the context of contemporary
      theory and provide insight into the development and timing of grief
      interventions.

PMID- 21895436
TI  - Perceived self-competency among the recently bereaved.
AB  - In this study, the authors identified personal resources, features of the marital
      relationship, and death circumstances that affected perceived self-competency
      among recently bereaved older adults. Data came from 328 widowed persons who
      participated in the "Living After Loss" project. Results suggested that those who
      had more personal resources--namely, income and good health--were the most
      competent in daily life tasks. Surprisingly, neither death forewarning nor
      marital quality improved competency after widowhood. Higher competency was
      associated with more positive mental health outcomes, suggesting that grief is
      complicated by the need to enhance and/or restore daily life activities as well
      as the need to deal with the sadness associated with the loss.

PMID- 21895437
TI  - Providing support at time of death from cancer: results of a 5-year post
      bereavement group study.
AB  - Despite advances in the quality and availability of hospice and palliative care
      for people with end stage cancers, research addressing the psychosocial needs of
      family members and concerned others during the dying process has been limited
      primarily to caregivers. In addition, many of these studies focused on the
      recently bereaved. In this study, the authors sought to broaden that perspective
      by examining the psychosocial needs of secondary survivors, a term that applies
      to caregivers, family members, and others who felt a caring bond with a dying
      person. A qualitative exploration of needs expressed by secondary survivors
      following the conclusion of a structured 8-week psychoeducational grief group
      experience revealed that secondary cancer survivors experience a sense of
      isolation and powerlessness that is often unrecognized by physicians, nurses,
      oncology social workers, or other health care professionals. Furthermore, these
      secondary survivors needed support that extends well beyond activities that are
      traditionally associated with the physical and emotional care of the dying.
      Social work intervention strategies directed toward helping secondary survivors
      assert personal needs, develop greater proximity with the health care team, and
      prepare for the processes associated with end-of-life may be helpful later during
      bereavement.

PMID- 21895438
TI  - Risks for complicated grief in family caregivers.
AB  - Complicated grief (CG) is a recently recognized disorder experienced by the
      bereaved and characterized by intense distress that interferes with functioning.
      Estimates indicate that about 20 % of bereaved individuals may develop CG. Family
      caregivers of those who are chronically ill may face unique risks for CG, such as
      pre-death stressors associated with caregiving. In this article, existing
      literature on CG in family caregivers is reviewed to identify pre-bereavement
      risk factors for the disorder. Implications for practice are also discussed,
      including both preventive interventions that could be instituted before the ill
      person's death and therapeutic techniques for treating CG after the death.

PMID- 21895439
TI  - Disoriented grief: a lens through which to view the experience of Katrina
      evacuees.
AB  - Many studies on the impact of natural disasters have focused primarily on
      immediate stress reactions and posttraumatic stress disorder (PTSD) symptoms
      rather than on evacuees' stories of grief and loss. Known categories of grief and
      loss do not fully capture the experiences of disaster survivors as evidenced by
      interviews of Hurricane Katrina evacuees in Austin, Texas. This article will
      describe their experiences through a resultant framework of Disoriented Grief.

PMID- 21895440
TI  - Bereavement, cognitive-emotional processing, and coping with the loss: a study of
      Indian and Japanese students.
AB  - Campus suicides have increased manifold across academic institutions, often
      leaving unresolved bereavement issues in these institutions, primarily because
      students are supposed to carry on with their daily activities with little or no
      time and attention paid to this necessary process. In this study, the role of
      cognitive-emotional processes in coping, especially when one is grieving a death,
      was investigated through a comparison between 40 bereaved Japanese and Indian
      female college students. The participants were assessed for resilience, cognitive
      emotional regulation, posttraumatic cognition, and coping strategies in the
      aftermath of the suicide death of someone close. Positive reappraisal mediated
      the relationship between resilience and proactive coping, whereas negative
      cognitions about the self mediated the relationship between resilience and
      proactive as well as reflective coping. The participants from the two cultures
      differed significantly on resilience, with Indians scoring higher than Japanese
      young adults. The findings are analyzed in light of the coping with distressful
      life events model and could have possible implications for social workers and/or
      mental health professionals in terms of acceptability of interventions.

PMID- 21895441
TI  - Introduction. Volcanism and astrobiology: life on earth and beyond.

PMID- 21895442
TI  - Putative fossilized fungi from the lithified volcaniclastic apron of Gran
      Canaria, Spain.
AB  - We report the discovery of fossilized filamentous structures in samples of the
      lithified, volcaniclastic apron of Gran Canaria, which were obtained during Leg
      157 of the Ocean Drilling Program (ODP). These filamentous structures are 2-15
      MUm in diameter and several hundred micrometers in length and are composed of Si,
      Al, Fe, Ca, Mg, Na, Ti, and C. Chitin was detected in the filamentous structures
      by staining with wheat germ agglutinin dye conjugated with fluorescein
      isothiocyanate (WGA-FITC), which suggests that they are fossilized fungal hyphae.
      The further elucidation of typical filamentous fungal morphological features,
      such as septa, hyphal bridges, and anastomosis and their respective sizes,
      support this interpretation. Characteristic structures that we interpreted as
      fossilized spores were also observed in association with the putative hyphae. The
      fungal hyphae were found in pyroxene phenocrysts and in siderite pseudomorphs of
      a basalt breccia. The fungal colonization of the basalt clasts occurred after the
      brecciation but prior to the final emplacement and lithification of the sediment
      at ~16-14 Ma. The siderite appears to have been partially dissolved by the
      presence of fungal hyphae, and the fungi preferentially colonized Fe-rich
      carbonates over Fe-poor carbonates (aragonite). Our findings indicate that fungi
      may be an important geobiological agent in subseafloor environments and an
      important component of the deep subseafloor biosphere, and that hydrothermal
      environments associated with volcanism can support a diverse ecosystem, including
      eukaryotes.

PMID- 21895443
TI  - Following the kinetics: iron-oxidizing microbial mats in cold icelandic volcanic
      habitats and their rock-associated carbonaceous signature.
AB  - Icelandic streams with mean annual temperatures of less than 5  degrees C, which
      receive the cationic products of basaltic rock weathering, were found to host
      mats of iron-cycling microorganisms. We investigated two representative sites.
      Iron-oxidizing Gallionella and iron-reducing Geobacter species were present. The
      mats host a high bacterial diversity as determined by culture-independent
      methods. beta-Proteobacteria, Actinobacteria, alpha-Proteobacteria, and
      Bacteroidetes were abundant microbial taxa. The mat contained a high number of
      phototroph sequences. The carbon compounds in the mat displayed broad G and D
      bands with Raman spectroscopy. This signature becomes incorporated into the
      weathered oxidized surface layer of the basaltic rocks and was observed on rocks
      that no longer host mats. The presence of iron-oxidizing taxa in the stream
      microbial mats, and the lack of them in previously studied volcanic rocks in
      Iceland that have intermittently been exposed to surface water flows, can be
      explained by the kinetic limitations to the extraction of reduced iron from
      rocks. This type of ecosystem illustrates key factors that control the
      distribution of chemolithotrophs in cold volcanic environments. The data show
      that one promising sample type for which the hypothesis of the existence of past
      life on Mars can be tested is the surface of volcanic rocks that, previously,
      were situated within channels carved by flowing water. Our results also show that
      the carbonaceous signatures of life, if life had occurred, could be found in or
      on these rocks.

PMID- 21895444
TI  - Analysis of airway epithelial regeneration and repair following endobronchial
      brush biopsy in sheep.
AB  - Understanding the fundamental processes involved in repairing the airway wall
      following injury is fundamental to understanding the way in which these processes
      are perturbed during disease pathology. Indeed complex diseases such as asthma
      and chronic obstructive pulmonary disease (COPD) have at their core evidence of
      airway wall remodeling processes that play a crucial functional role in these
      diseases. The authors sought to understand the dynamic cellular events that occur
      during bronchial airway epithelial repair in sheep. The injury was induced by
      endobronchial brush biopsy (BBr), a process that causes epithelial debridement
      and induces a consequential repair process. In addition, the current experimental
      protocol allowed for the time-dependent changes in airway wall morphology to be
      studied both within and between animals. The initial debridement was followed by
      evidence of dedifferentiation in the intact epithelium at the wound margins,
      followed by proliferation of cells both within the epithelium and in the deeper
      wall structures, notably in association with the submucosal glands and smooth
      muscle bundles. Seven days after injury, although the airway wall was thickened
      at the site of damage, the epithelial layer was intact, with evidence of
      redifferentiation. These studies, in demonstrating broad agreement with previous
      studies in small animals, indicate the wider relevance of this system as a
      comparative model and should provide a solid basis upon which to further
      characterize the critical cellular and molecular interactions that underlie both
      effective restitution and pathological repair.

PMID- 21895445
TI  - Prolonged amelioration of acute lung allograft rejection by sequential
      overexpression of human interleukin-10 and hepatocyte growth factor in rats.
AB  - The effect of prolonged electroporation-mediated human interleukin-10 (hIL-10)
      overexpression 24 hours before transplantation, combined with sequential human
      hepatocyte growth factor (HGF) overexpression into skeletal muscle on day 5, on
      rat lung allograft rejection was evaluated. Left lung allotransplantation was
      performed from Brown-Norway to Fischer-F344 rats. Gene transfer into skeletal
      muscle was enhanced by electroporation. Three groups were studied: group I
      animals (n = 5) received 2.5 MUg pCIK-hIL-10 (hIL-10/CMV [cytomegalovirus] early
      promoter enhancer) on day -1 and 80 MUg pCIK-HGF (HGF/CMV early promoter
      enhancer) on day 5. Group II animals (n = 4) received 2.5 MUg pCIK-hIL-10 and
      pUbC-hIL-10 (hIL-10/pUbC promoter) on day -1. Control group III animals (n = 4)
      were treated by sham electroporation on days -1 and 5. All animals received daily
      nontherapeutic intraperitoneal dose of cyclosporin A (2.5 mg/kg) and were
      sacrificed on day 15. Graft oxygenation and allograft rejection were evaluated.
      Significant differences were found between study groups in graft oxygenation
      (Pao(2)) (P = .0028; group I vs. groups II and III, P < .01 each). Pao(2) was low
      in group II (31 +/- 1 mm Hg) and in group III controls (34 +/- 10 mm Hg), without
      statistically significant difference between these 2 groups (P = .54). In
      contrast, in group I, Pao(2) of recipients sequentially transduced with IL-10 and
      HGF plasmids was much improved, with 112 +/- 39 mm Hg (vs. groups II and III; P <
      .01 each), paralleled by reduced vascular and bronchial rejection (group I vs.
      groups II and III, P < .021 each). Sequential overexpression of anti-inflammatory
      cytokine IL-10, followed by sequential and overlapping HGF overexpression on day
      5, preserves lung function and reduces acute lung allograft rejection up to day
      15 post transplant as compared to prolonged IL-10 overexpression alone.

PMID- 21895446
TI  - Beta-adrenergic modulation of lung fluid balance in acute P aeruginosa pneumonia
      in rats.
AB  - OBJECTIVE: we investigated the effects of terbutaline, a beta(2)-adrenergic
      agonist, on lung permeability and alveolar fluid clearance (AFC) in acute lung
      injury (ALI). METHODS: the study was conducted in vivo on a rat model of P
      aeruginosa (Pa)-induced ALI. Rats were randomly divided into five groups: the
      control group (saline group), Pa and saline group, Pa and terbutaline treated
      group receiving intratracheal instillation of terbutaline at 10(-4) M, Pa and
      terbutaline plus propranolol treated group (terbutaline+propranolol group) and Pa
      and propranolol treated group (propranolol group). Hemodynamics, airway
      pressures, arterial blood gases, extravascular lung water, lung permeability to
      protein evaluated by the extravascular accumulation of (125)I-albumin (EPE),
      bacterial counts, and alveolar fluid clearance (AFC) were measured. RESULTS: 4.5
      hours after bacterial instillation, the lung wet-to-dry ratio and the EPE were
      significantly decreased in the terbutaline group compared to saline control group
      (respectively 4.31 +/- 0.51 g/g versus 5.99 +/- 0.5 g/g 4.18 +/- 0.25 g/g and 148
      +/- 68 MUL versus 349 +/- 97 MUL respectively p < 0.01). Treatment with
      terbutaline in the Pa-instilled group significantly increased basal AFC compared
      with the saline and Pa group, (respectively 22.3 +/- 1.3% versus 12.5 +/- 4.7%, p
      < 0.001). Intratracheal instillation of propranolol (10(-4) M) inhibited the
      effects of terbutaline on lung fluid balance. CONCLUSION: Exogenous instillation
      of beta2-adrenergic have a beneficial effect on lung fluid balance following Pa
      pneumonia in rats, by reducing pulmonary endothelial permeability and increasing
      alveolar fluid clearance. These data suggest that exogenous beta-adrenergic
      therapy can protect against alveolar edema formation in acute P aeruginosa
      pneumonia.

PMID- 21895447
TI  - Therapeutic role of terbutaline in a rat whole-lung lavage model.
AB  - Whole-lung lavage (WLL) is the preferred therapy for patients with pulmonary
      alveolar proteinosis (PAP). However, WLL can cause fluid retention, surfactant
      lost, and hypoxia. Terbutaline has been shown to accelerate the rate of alveolar
      fluid clearance and augment surfactant secretion. The present study aimed at
      investigating effects of terbutaline and oxygen ventilation in rats with WLL.
      Forty rats were randomly divided into control, ventilation, NS (normal saline) +
      ventilation, LT (terbutaline in low concentration, 10(-4) M) + ventilation, and
      HT (terbutaline in high concentration, 10(-3) M) + ventilation groups. The left
      thoracic cavity was opened and a cannula was inserted into the left bronchus. The
      left lung was ventilated, while the right lung was lavaged. Arterial blood gas,
      electrocardiogram, histological changes, and wet/dry ratio of lung tissues were
      examined. The concentrations of total protein (TP), total phospholipids (TPL),
      and disaturated phosphatidylcholine (DSPC) in recovery fluid were measured. For
      the in vitro study, alveolar type II (ATII) cells were isolated from healthy male
      rats, incubated for 24 hours, and divided into control, LT, and HT groups and
      exposed to different concentration of terbutaline (10(-4) and 10(-3) M) for 2
      hours, followed by measuring sodium-potassium adenosine triphosphatase
      (Na(+),K(+)-ATPase) activity. Oxygen ventilation significantly increased
      Pao(2)/Fio(2) after lavage in the ventilation group, as compared to control group
      (249.4 +/- 7.9 vs 210.6 +/- 9.4; P = .001). Compared with NS + venlitation group,
      a higher concentration of terbutaline decreased the wet/dry ratio of lung tissues
      (5.0 +/- 0.1 vs 5.6 +/- 0.1; P = .007), increased the concentrations of TPL
      (175.9 +/- 14.0 vs 162.0 +/- 6.8 mg/L; P = .031) and DSPC (93.2 +/- 6.9 vs 70.9
      +/- 6.2 mg/L, P = .0001) in the recovery fluid, and alleviated hypoxia
      significantly. Terbutaline in both low and high doses increased Na(+),K(+)-ATPase
      activity in ATII cells (62.5 +/- 2.4 and 62.6 +/- 2.8 vs 32.2 +/- 2.1 mmol/h/mg
      protein; P < .01). Theses results show that the administration of terbutaline
      facilitates alveolar fluid absorption and increases surfactant secretion during
      lung lavage, the former is partly driven by increasing Na(+),K(+)-ATPase
      activity. The modified lavage method, with the use of terbutaline and oxygen
      ventilation, is one of potential therapies for patients with PAP.

PMID- 21895448
TI  - Impact of lipophilic antioxidants and level of antibodies against oxidized low
      density lipoprotein in Polish children with phenylketonuria.
AB  - The treatment of phenylketonuria (PKU) patients constitutes a phenylalanine (Phe)
      intake restriction in their diet, which is achieved by adding a special Phe-free
      amino acid mixture to the diet. It has been reported that this diet could have
      some micronutrient deficiency. Several authors have also reported an increased
      oxidative stress or impaired antioxidant status in human and experimental PKU.
      Our project assessed the concentrations of retinol, alpha-tocopherol, coenzyme
      Q10, and anti-oxidized low-density lipoprotein (ox-LDL) antibodies in PKU
      children's plasma. It was found that retinol concentration in PKU children
      remains within the norm despite a low intake. The lower plasma alpha-tocopherol
      concentration in PKU children compared with normal children was associated with
      the lower level of antibodies against ox-LDL. This raises the question whether
      higher than observed circulatory alpha-tocopherol is indeed beneficial to lower
      plasma ox-LDL levels. Further studies are needed to explain the genetic factor in
      PKU patients (e.g., CD36/FAT polymorphism gene). The open clinical question is
      whether daily supplementation of alpha-tocopherol changes the PKU patients' level
      of antibodies against ox-LDL.

PMID- 21895449
TI  - Late-life bereavement and complicated grief: a proposed comprehensive framework.
AB  - OBJECTIVES: The construct of complicated grief (CG) has garnered increased
      empirical attention since it has been proposed as a diagnostic category for the
      upcoming Diagnostic and Statistical Manual of Mental Disorders-V. The aim of this
      article is to critically examine construct validity in light of a proposed
      conceptual framework, with special emphasis on understanding late-life
      bereavement. METHOD: This is a review article that critically examined current
      bereavement and grief models. We explored discriminant and convergent validity
      between CG and uncomplicated grief (UG) and other psychopathological constructs
      in terms of symptom intensity, symptom trajectories, bereavement outcomes, and
      treatment response. RESULTS: The findings from this review show mixed support for
      differentiating CG from other outcomes of bereavement for the following reasons:
      (1) a clear boundary between CG and UG has not been adequately supported, (2)
      symptoms of CG and bereavement-related depression and anxiety overlap, although
      there is some evidence of incremental validity in that CG symptoms predict global
      functioning above and beyond symptoms of depression, and (3) the treatment
      literature demonstrated that general grief interventions and treatment targeted
      for improving depression are ineffective at treating symptoms of CG, whereas
      interventions specially tailored to treating CG have been moderately effective.
      The findings also emphasize the importance of considering pre-bereavement
      circumstances, such as preexisting depression, in the conceptualization of
      broader bereavement outcome. CONCLUSION: There were mixed findings supporting the
      construct validation of CG. A comprehensive framework that emphasizes pre
      bereavement circumstances was proposed in order to better predict various grief
      trajectories and outcomes of late-life loss.

PMID- 21895450
TI  - Self-compassion and social anxiety disorder.
AB  - Self-compassion refers to having an accepting and caring orientation towards
      oneself. Although self-compassion has been studied primarily in healthy
      populations, one particularly compelling clinical context in which to examine
      self-compassion is social anxiety disorder (SAD). SAD is characterized by high
      levels of negative self-criticism as well as an abiding concern about others'
      evaluation of one's performance. In the present study, we tested the hypotheses
      that: (1) people with SAD would demonstrate less self-compassion than healthy
      controls (HCs), (2) self-compassion would relate to severity of social anxiety
      and fear of evaluation among people with SAD, and (3) age would be negatively
      correlated with self-compassion for people with SAD, but not for HC. As expected,
      people with SAD reported less self-compassion than HCs on the Self-Compassion
      Scale and its subscales. Within the SAD group, lesser self-compassion was not
      generally associated with severity of social anxiety, but it was associated with
      greater fear of both negative and positive evaluation. Age was negatively
      correlated with self-compassion for people with SAD, whereas age was positively
      correlated with self-compassion for HC. These findings suggest that self
      compassion may be a particularly important target for assessment and treatment in
      persons with SAD.

PMID- 21895451
TI  - Dyspnea review for the palliative care professional: assessment, burdens, and
      etiologies.
AB  - BACKGROUND: Dyspnea is a common symptom experienced by many patients with
      chronic, life-threatening, and/or life-limiting illnesses. Although it can be
      defined and measured in several ways, dyspnea is best described directly by
      patients through regular assessment, as its burdens exert a strong influence on
      the patient's experience throughout the trajectory of serious illness. Its
      significance is amplified due to its impact on family and caregivers. DISCUSSION:
      Anatomic and physiologic changes associated with dyspnea, and cognitive
      perceptions related to patients and the underlying disease, provide insights into
      how to shape interventions targeting this oppressive symptom. Additionally, as
      described in the concept of "total dyspnea," the complex etiology and
      manifestation of this symptom require multidisciplinary treatment plans that
      focus on psychological, social, and spiritual distress as well as physical
      components. Several validated assessment tools are available for clinical and
      research use, and choice of method should be tailored to the individual patient,
      disease, and care setting in the context of patient-centered care. CONCLUSION:
      This article, the first in a two-part series, reviews the identification and
      assessment of dyspnea, the burden it entails, and the underlying respiratory and
      nonrespiratory etiologies that may cause or exacerbate it.

PMID- 21895452
TI  - Pain outcomes of inpatient pain and palliative care consultations: differences by
      race and diagnosis.
AB  - BACKGROUND: Pain management disparities exist among patients not receiving
      palliative care. We examined pain outcomes for disparities among patients
      receiving palliative care. METHODS: At a 542-bed teaching hospital in Honolulu,
      The Queens' Medical Center Pain and Palliative Care Department collected patient
      characteristics and pain severity (initial, final) for each consultation from
      2005 through 2009. Analyses compared pain levels by race (white, Asian,
      Hawaiian/Pacific Islander [PI], other) and consultation diagnosis (cancer,
      noncancer medical, surgical [59% orthopedic], other). Multiple regression models
      analyzed factors associated with lower final pain levels and pain reduction.
      RESULTS: Study population included 4658 patients. No final pain was reported by
      more non-white patients (33%-39%) than white (27%, p<0.0001) and more cancer and
      noncancer medical patients (45%-54%) than surgical/other patients (20%-31%,
      p<0.0001). Asian (adjusted odds ratio [aOR] 1.24; 95% confidence interval [CI]
      1.06-1.46; p=0.007) and PI (aOR 1.46, 95% CI 1.20-1.77, p=0.0001) races had
      increased likelihoods of lower final pain severity versus whites, controlling for
      age, gender, Karnofsky score, preconsult length of stay, and initial pain
      severity. Surgical diagnoses had decreased likelihood of lower final pain levels
      versus cancer (aOR 0.38, 95% CI 0.32-0.46, p<0.0001). Among 2304 patients
      reporting moderate/severe initial pain, 1738 (75.4%) reported pain reduction to
      mild/no final pain. PI race was associated with pain reduction versus whites (aOR
      1.57, 95% CI 1.17-2.10, p=0.003). Surgical diagnoses had decreased likelihood of
      pain reduction vs. cancer (aOR 0.52, 95% CI 0.39-0.71, p<0.0001). CONCLUSION:
      Pain outcomes were similar or better among non-white races than whites. Surgical
      patients reported more final pain than cancer patients.

PMID- 21895453
TI  - Palliative medicine and decision science: the critical need for a shared agenda
      to foster informed patient choice in serious illness.
AB  - Assisting patients and their families in complex decision making is a
      foundational skill in palliative care; however, palliative care clinicians and
      scientists have just begun to establish an evidence base for best practice in
      assisting patients and families in complex decision making. Decision scientists
      aim to understand and clarify the concepts and techniques of shared decision
      making (SDM), decision support, and informed patient choice in order to ensure
      that patient and family perspectives shape their health care experience. Patients
      with serious illness and their families are faced with myriad complex decisions
      over the course of illness and as death approaches. If patients lose capacity,
      then surrogate decision makers are cast into the decision-making role. The fields
      of palliative care and decision science have grown in parallel. There is much to
      be gained in advancing the practices of complex decision making in serious
      illness through increased collaboration. The purpose of this article is to use a
      case study to highlight the broad range of difficult decisions, issues, and
      opportunities imposed by a life-limiting illness in order to illustrate how
      collaboration and a joint research agenda between palliative care and decision
      science researchers, theorists, and clinicians might guide best practices for
      patients and their families.

PMID- 21895454
TI  - Sterols from Sargassum oligocystum, a brown algae from the Persian Gulf, and
      their bioactivity.
AB  - Sargassum oligocystum (Heterokontophyta) is one of the most abundant algae
      distributed in the Persian Gulf. In this study, the cytotoxic effects of this
      algae on brine shrimp larvae were evaluated and the main sterols of the algae
      identified. Separation and purification of the compounds was carried out using
      silica gel column chromatography and HPLC to obtain eight pure compounds, 1-8.
      Structural elucidation of the constituents was based on the data obtained from
      (1)H-NMR, (13)C-NMR, HSQC, HMBC, DEPT and EI-MS. The compounds separated from S.
      oligocystum were identified as 22-dehydrocholesterol (1), cholesterol (2),
      fucosterol (3), 29-hydroperoxystigmasta-5,24(28)-dien-3beta-ol (4), 24
      hydroperoxy-24-vinylcholesterol (5), a mixture of 24(S)-hydroxy-24
      vinylcholesterol (6) and 24(R)-hydroxy-24-vinylcholesterol (7), and ostreasterol
      (8) based on their spectral data and from comparison with those previously
      reported in the literature.

PMID- 21895455
TI  - The in vivo anti-plasmodial activity of haliclonacyclamine A, an alkaloid from
      the marine sponge, Haliclona sp.
AB  - The compound haliclonacyclamine A was isolated from the Haliclona sponge at
      Solomon Islands. It acts as a powerful in vitro and in vivo anti-plasmodial agent
      against the chloroquine-resistant Plasmodium falciparum strain FCB1and Plasmodium
      vinckei petteri-infected mice, respectively.

PMID- 21895456
TI  - In vitro antiviral activities of extracts derived from Daucus maritimus seeds.
AB  - The antiviral activities of extracts from Daucus maritimus seeds were
      investigated against the reverse transcriptase of human immunodeficiency virus
      (HIV) type 1 and a panel of RNA-dependent RNA polymerases of dengue virus, West
      Nile virus (WNV) and hepatitis C virus (HCV). The extracts showed moderate to
      potent inhibition rates against the four viral polymerases. The ethyl acetate
      extract exhibited a potent inhibitory effect against WNV's RdRp, with an IC50
      value of 8 ug mL-1. The F2 fraction exhibited potent inhibitory activity against
      WNV and HCV's RdRps, with IC50 values 1 and 5 ug mL-1, respectively. The P2
      fraction also showed potent inhibitory effects on WNV and HCV's RdRps, with IC50
      values 2.7 and 4 ug mL-1, respectively. The results suggest that these extracts
      are candidates for the development of new anti-WNV RpDp and anti-HCV RpDp agents.

PMID- 21895457
TI  - Comparison of antimicrobial activities of naphthoquinones from Impatiens
      balsamina.
AB  - Lawsone (1), lawsone methyl ether (2), and methylene-3,3'-bilawsone (3) are the
      main naphthoquinones in the leaf extracts of Impatiens balsamina L.
      (Balsaminaceae). Antimicrobial activities of these three naphthoquinones against
      dermatophyte fungi, yeast, aerobic bacteria and facultative anaerobic and
      anaerobic bacteria were evaluated by determination of minimal inhibitory
      concentrations (MICs) and minimal bactericidal or fungicidal concentrations (MBCs
      or MFCs) using a modified agar dilution method. Compound 2 showed the highest
      antimicrobial activity. It showed antifungal activity against dermatophyte fungi
      and Candida albicans with the MICs and MFCs in the ranges of 3.9-23.4 and 7.8
      23.4 ug mL(-1), respectively, and also had some antibacterial activity against
      aerobic, facultative anaerobic and anaerobic bacteria with MICs in the range of
      23.4-93.8, 31.2-62.5 and 125 ug mL(-1), respectively. Compound 1 showed only
      moderate antimicrobial activity against dermatophytes (MICs and MFCs in the
      ranges of 62.5-250 and 125-250 ug mL(-1), respectively), but had low potency
      against aerobic bacteria, and was not active against C. albicans and facultative
      anaerobic bacteria. In contrast, 3 showed significant antimicrobial activity only
      against Staphylococus epidermidis and Bacillus subtilis (MIC and MBC of 46.9 and
      93.8 ug mL(-1), respectively).

PMID- 21895458
TI  - Investigating the predictive validity of implicit and explicit measures of
      motivation on condom use, physical activity and healthy eating.
AB  - The literature on health-related behaviours and motivation is replete with
      research involving explicit processes and their relations with intentions and
      behaviour. Recently, interest has been focused on the impact of implicit
      processes and measures on health-related behaviours. Dual-systems models have
      been proposed to provide a framework for understanding the effects of explicit or
      deliberative and implicit or impulsive processes on health behaviours. Informed
      by a dual-systems approach and self-determination theory, the aim of this study
      was to test the effects of implicit and explicit motivation on three health
      related behaviours in a sample of undergraduate students (N = 162). Implicit
      motives were hypothesised to predict behaviour independent of intentions while
      explicit motives would be mediated by intentions. Regression analyses indicated
      that implicit motivation predicted physical activity behaviour only. Across all
      behaviours, intention mediated the effects of explicit motivational variables
      from self-determination theory. This study provides limited support for dual
      systems models and the role of implicit motivation in the prediction of health
      related behaviour. Suggestions for future research into the role of implicit
      processes in motivation are outlined.

PMID- 21895459
TI  - Follow-up effects of social comparison information on the quality of life of
      cancer patients: the moderating role of social comparison orientation.
AB  - OBJECTIVE: To examine how social comparison orientation (SCO) moderates the
      effects of three types of social comparison information on the global quality of
      life of cancer patients 2 weeks and 3 months later. DESIGN: Cancer patients
      (n=226) were provided with social comparison information just prior to undergoing
      radiation therapy, using audiotapes. Each participant was confronted with one of
      three tapes: (1) focusing on procedural aspects, (2) focusing on emotional
      reactions and (3) focusing on coping strategies. MAIN OUTCOME MEASURES: Quality
      of life as measured with the Cantril self-anchoring scale [Cantril, H. (1965).
      The pattern of human concerns. New Brunswick, NJ: Rutgers University Press].
      RESULTS: With increasing SCO, a lower quality of life was reported after
      listening to the emotion tape, while a higher quality of life was reported after
      listening to the coping tape. These effects were found 2 weeks as well as 3
      months after the radiation therapy had ended. CONCLUSION: Social comparison
      information may have longitudinal effects on quality of life, but these effects
      are to an important extent dependent on the nature of the information and
      individual differences in SCO.

PMID- 21895460
TI  - The anti-biofilm activity secreted by a marine Pseudoalteromonas strain.
AB  - Bacterial biofilms occur on all submerged structures in marine environments. The
      authors previously reported that the marine bacterium Pseudoalteromonas sp. 3J6
      secretes antibiofilm activity. Here, it was discovered that another
      Pseudoalteromonas sp. strain, D41, inhibited the development of strain 3J6 in
      mixed biofilms. Confocal laser scanning microscope observations revealed that the
      culture supernatant of strain D41 impaired biofilm formation of strain 3J6 and
      another marine bacterium. A microtiter plate assay of the antibiofilm activity
      was set up and validated with culture supernatants of Pseudoalteromonas sp. 3J6.
      This assay was used to determine the spectra of action of strains D41 and 3J6.
      Each culture supernatant impaired the biofilm development of 13 marine bacteria
      out of 18. However, differences in the spectra of action and the physical
      behaviours of the antibiofilm molecules suggest that the latter are not
      identical. They nevertheless share the originality of being devoid of
      antibacterial activity against planktonic bacteria.

PMID- 21895461
TI  - Preparation of a genipin blue from egg protein and genipin.
AB  - Genipin blue is a pigment prepared from the reaction of genipin with amino acid.
      We describe herein a new method used to prepare genipin blue, water-soluble blue
      pigments, through the reaction of hen egg protein with genipin. The effects of
      reaction time, reaction temperature, the pH value of the solution and the mass
      ratio of the reactants on the preparation are studied. One part of genipin
      reacted with eight parts of hen egg protein (w/w) in water (pH value of reaction
      system 7.5) at 60 degrees C for 96 h and gave blue pigments with the maximum
      colour value of 146.2. The blue pigments showed identical absorption activity in
      UV spectroscopy (lambda(max )= 584 nm) to that of gardenia blue pigments, which
      were prepared from the reaction of genipin with amino acid.

PMID- 21895462
TI  - Testing mediator variables in a resistance training intervention for obese adults
      with type 2 diabetes.
AB  - A poor understanding of behaviour change mechanisms has hindered the development
      of effective physical activity interventions. The aim of this study was to
      identify potential mediators of change in a home-based resistance training (RT)
      program for obese individuals with type 2 diabetes. Obese individuals with type 2
      diabetes (N = 48) were randomly allocated to either an RT intervention (n = 27)
      or a control group (n = 21) for the 16-week study period. The study sample
      included 16 men and 32 women and the mean age of participants was 54.4 (+/-11.7)
      years. Participants in the RT group received a multi-gym and dumbbells and home
      supervision from a certified personal trainer. RT behaviour was measured using a
      modified Godin Leisure Time Questionnaire. Social-cognitive constructs were
      measured and tested in a mediating variable framework using a product-of
      coefficients test. The intervention had a significant effect on RT behaviour (p <
      0.001) and muscular strength (p < 0.001). The intervention had a significant
      effect on RT planning strategies (p < 0.01), which mediated the effect of the
      intervention on RT behaviour. The home-based RT program successfully targeted
      participants' RT planning strategies which contributed to their exercise
      adherence.

PMID- 21895463
TI  - Lamiolactone, a new iridoid lactone from Lamiophlomis rotata.
AB  - Lamiolactone (1), a new iridoid lactone, together with five known iridoids, were
      isolated from the 95% EtOH extract of the roots of Lamiophlomis rotata. The
      structure of 1 was elucidated to be methyl antirrhinolide-4-carboxylate on the
      basis of spectroscopic analysis.

PMID- 21895464
TI  - Fatty acids of Rhodobryum ontariense (Bryaceae).
AB  - The chemical composition of Rhodobryum ontariense (Kindb.) Kindb. has not been
      previously investigated. Fatty acids of this moss were analysed qualitatively and
      quantitatively with an aim to identify its corresponding pattern. A total of
      eight fatty acids were identified including two acetylenic ones: 9,12,15
      octadecatrien-6-ynoic acid (42.26%), alpha-linolenic acid (20.32%), palmitic acid
      (14.31%), 9,12-octadecadienoic-6-ynoic acid (13.31%), linoleic acid (5.25%),
      oleic acid (2.47%), stearic acid (1.14%) and gamma-linolenic acid (0.92%). To our
      knowledge, this is the first record of acetylenic fatty acids in the genus
      Rhodobryum. In general, acetylenic fatty acids vary considerably among different
      moss groups and have been used as a chemotaxonomic character in bryophyte
      classifications. Other species of Rhodobryum from Asia have been traditionally
      used in ethno medicine by indigenous cultures. Two fatty acids of those reported
      here, 9,12,15-octadecatrien-6-ynoic and alpha-linolenic acid, have known cardio
      protective activity, which supports respective claims of traditional herbal use
      of these mosses.

PMID- 21895465
TI  - Reproductive immunology: the clinical view.

PMID- 21895466
TI  - Sidestepping maternal antibody: a lesson from measles virus vaccination.

PMID- 21895467
TI  - Murine trophoblast stem cells and their immunological capabilities.

PMID- 21895469
TI  - Cinryze (C1-inhibitor) for the treatment of hereditary angioedema.
AB  - Cinryze is a pasteurized, nanofiltered plasma derived concentrate of C1-inhibitor
      (pdC1-INH) licensed for the prophylactic treatment of hereditary angioedema. In a
      double-blind placebo-controlled crossover trial to evaluate Cinryze as
      prophylaxis, the frequency of attacks was halved (6.26 per 12 weeks on Cinryze
      versus 12.73 per 12 weeks on placebo). Furthermore, attacks were generally milder
      and of shorter duration. For treatment of acute attacks in patients receiving
      Cinryze, 1000 units, within 4 h of the start of an attack, the estimated time to
      the onset of unequivocal relief was reduced to 2 h, compared with more than 4 h
      in those treated with placebo. Cinryze and other similar products are going to
      change the future management of hereditary angioedema and have potential in other
      areas of medicine.

PMID- 21895470
TI  - New frontiers in reproductive immunology research: bringing bedside problems to
      the bench.
AB  - The 31st Annual Meeting of the American Society for Reproductive Immunology
      provided an excellent platform for basic and clinical scientists to brainstorm on
      current reproductive health issues such as repeated implantation and pregnancy
      failure, preterm birth, preeclampsia and genital tract infections such as HIV.
      The goal of the meeting was to foster cross-pollination of ideas as well as to
      encourage participation of young investigators in the field. The conference was
      preceded by the 4th Annual Post-Graduate Workshop with the theme of bringing
      bedside problems to the bench and facilitating collaboration between clinicians
      and basic scientists. Christopher Davies and Richard Bronson chaired the
      conference, which hosted approximately 180 delegates representing more than 26
      countries across Asia, Australia, Latin America, Europe and North America.

PMID- 21895471
TI  - Prenatal programming of the innate immune response following in utero exposure to
      inflammation: a sexually dimorphic process?
AB  - Maternal infection and inflammation are common events during pregnancy. This
      article documents evidence that suggests such inflammation compromises the
      development of the fetal innate immune response, in support of an in utero
      origins hypothesis of neonatal and childhood inflammatory disease. The potential
      for this response to exhibit sex specificity is also explored, based on evidence
      of sexually dimorphic placental responses to maternal inflammation.

PMID- 21895472
TI  - Dendritic cell function at the maternal-fetal interface.
AB  - Understanding the evolutionary adaptation of the immune system to the developing
      fetus and placenta represents one of the most fascinating problems in
      reproductive biology. Recent work has focused on how the behavior of dendritic
      cells (DCs) is altered at the maternal-fetal interface to suit the unique
      requirements of pregnancy. This work has provided a significant new perspective
      into the long-standing immunological paradox of fetomaternal tolerance, and has
      opened up a new and intriguing area of research into the potential trophic role
      of uterine DCs in the peri-implantation period. Further research on the biology
      of uterine DCs promises to give insight into the pathogenesis of many clinically
      important disorders of pregnancy.

PMID- 21895473
TI  - Understanding the link between the IL-6 cytokine family and pregnancy:
      implications for future therapeutics.
AB  - Cytokines are involved in almost all processes during the menstrual cycle, the
      fertilization period and pregnancy. They are expressed in numerous reproduction
      related body fluids and tissues. Disorders of cytokine expression patterns may
      cause pregnancy pathologies. Therefore, cytokines have the potential as new
      biomarkers in different body compartments for a variety of such pathologies.
      Furthermore, cytokines may also serve to treat fertility and pregnancy disorders.
      The IL-6-like family of cytokines is an intensively investigated group of
      cytokines with well-accepted functions in fertility and pregnancy. This article
      summarizes current knowledge on IL-6-like cytokines in regard of their role in
      reproduction and their potential for new strategies in the treatment of
      reproductive pathologies.

PMID- 21895475
TI  - The role of mast cells in male infertility.
AB  - Increased numbers of mast cells (MCs) were described in the testes of males
      exhibiting infertility many years ago. Since beneficial effects of treatment with
      MC blockers on impaired male fertility were reported, more attention has been
      drawn on the role of MCs in the male reproductive tract. The main interest is
      focused on testicular MCs, however MCs also occur in the epididymis and seminal
      fluid, which may be relevant for fertility as well. The increase in testicular
      MCs in close contact to the seminiferous tubules indicates a relationship between
      MC proliferation and a dysfunction of the blood-testis barrier. Activated MCs not
      only coincide with fibrotic events, but also with elevated numbers of several
      types of immune cells in the testes of infertile men and may, therefore, be
      involved in the pathogenesis of testicular inflammatory processes as well.
      Outside the testis, MCs have really been assigned a key role in chronic
      protatitis/chronic pelvic pain syndrome. The occurrence of MCs in the seminal
      plasma of fertile/infertile men and negative effects on sperm functions has not
      been clarified so far and require further investigation. Optimistic reports on
      the beneficial effects of the treatment with MC blockers on disturbed male
      fertility also warrant further confirmation.

PMID- 21895476
TI  - Systemic lupus erythematosus, regulatory T cells and pregnancy.
AB  - Systemic lupus erythematosus (SLE) is the most common autoimmune disease
      affecting women of reproductive age and is associated with poor maternal and
      fetal outcomes. CD4(+)CD25(+) Treg cells are a subset of T lymphocytes with
      potent immunosuppressive activity that play crucial roles in controlling
      immunological self tolerance. Evidence suggests that they are augmented in
      pregnancy, especially in the first trimester, suggesting an important role in
      early placental development. The literature describing Treg cells in SLE is
      conflicting, but SLE is associated with reduced numbers and functionally
      defective Treg cells, which may predispose pregnant women with the disease to
      pregnancy complications. This article discusses the role of Treg cells in SLE and
      pregnancy, and how these cells may contribute to poor pregnancy outcome in SLE
      affected women.

PMID- 21895474
TI  - Immune interactions in endometriosis.
AB  - Endometriosis is a common, complex gynecologic disorder characterized by the
      presence of endometrial glands and stroma at extrauterine (ectopic) sites. In
      women who develop this disease, alterations in specific biological processes
      involving both the endocrine and immune systems have been observed, which may
      explain the survival and growth of displaced endometrial tissue in affected
      women. In the past decade, a considerable amount of research has implicated a
      role for alterations in progesterone action at both eutopic and ectopic sites of
      endometrial growth which may contribute to the excessive inflammation associated
      with progression of endometriosis; however, it remains unclear whether these
      anomalies induce the condition or are simply a consequence of the disease
      process. In this article, we summarize current knowledge of alterations within
      the immune system of endometriosis patients and discuss how endometrial cells
      from women with this disease not only have the capacity to escape
      immunosurveillance, but also use inflammatory mechanisms to promote their growth
      within the peritoneal cavity. Finally, we discuss evidence that exposure to an
      environmental endocrine disruptor, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin,
      can mediate the development of an endometrial phenotype that exhibits both
      reduced progesterone responsiveness and hypersensitivity to proinflammatory
      stimuli mimicking the endometriosis phenotype. Future studies in women with
      endometriosis should consider whether a heightened inflammatory response within
      the peritoneal microenvironment contributes to the development and persistence of
      this disease.

PMID- 21895477
TI  - Clinical implication of recent advances in our understanding of IL-17 and
      reproductive immunology.
AB  - The identification of a novel helper T (Th)-cell subset, the IL-17-producing Th
      (Th17) cells, has provided new insight into our understanding of the molecular
      mechanisms of reproduction. IL-17 has an important role in induction of the
      protective immune response against extracellular bacteria or fungal pathogens.
      Th17 cells seem to participate in successful pregnancy processes. Th17 cells also
      play a pivotal role in pathogenesis of endometriosis, miscarriage, preterm labor
      and preeclampsia. Recent data show the reciprocal development of pathways between
      Th1/Th17 subsets and between Th17/Treg subsets, and the imbalance of Th17/Treg
      development has been reported in recurrent pregnancy loss and preeclampsia.

PMID- 21895479
TI  - Anti-inflammatory mediators as physiological and pharmacological regulators of
      parturition.
AB  - Increasing evidence highlights parturition as an inflammatory event characterized
      by leukocyte influx and proinflammatory mediator production in the intrauterine
      environment. While the mechanisms responsible for the initiation of this
      inflammatory cascade are not well understood, it is clear that these inflammatory
      events must be tightly regulated as the premature activation of these
      inflammatory signals is associated with adverse pregnancy outcomes, such as
      preterm labor, which is the leading cause of neonatal mortality and morbidity. In
      this article we highlight the importance of anti-inflammatory factors in
      regulating the inflammatory events surrounding parturition and discuss the use of
      anti-inflammatory mediators as potential novel therapeutic agents in the
      treatment of inflammation-induced preterm labor.

PMID- 21895480
TI  - Thyroid physiology and autoimmunity in pregnancy and after delivery.
AB  - During pregnancy and after delivery, the maternal thyroid gland faces several
      metabolic, hemodynamic and immunologic changes. In this article we first
      summarize the current knowledge on the physiologic adaptation of the healthy
      thyroid to pregnancy, including variations of thyroid-stimulating hormone and
      free thyroid hormones, as well as variations of thyroid volume. Our second aim is
      to illustrate the background of thyroid autoimmunity in this period, which
      characteristically ameliorates during pregnancy and aggravates after delivery.
      Although rare during pregnancy, Graves' disease is the most frequent cause of
      hyperthyroidism, while Hashimoto's thyroiditis is the most frequent cause for
      hypothyroidism. Both types of thyroid dysfunction may lead to detrimental
      complications in mother and child and therefore timely recognition and treatment
      is essential. Postpartum autoimmunity most frequently exacerbates in the form of
      postpartum thyroiditis, which presents with diverse clinical presentations and
      may lead to permanent hypothyroidism.

PMID- 21895478
TI  - Receptor-activating autoantibodies and disease: preeclampsia and beyond.
AB  - The research reviewed in this article provides examples of autoantibody-mediated
      receptor activation that likely contributes to disease. The classic example is
      Graves' hyperthyroidism, in which autoantibodies activate the thyroid-stimulating
      hormone receptor resulting in overproduction of thyroid hormones. Other
      compelling examples come from the cardiovascular literature and include agonistic
      autoantibodies targeting the cardiac beta(1)-adrenergic receptor, which are
      associated with dilated cardiomyopathy. Autoantibodies capable of activating
      alpha(1)-adrenergic receptors are associated with refractory hypertension and
      cardiomyopathy. A prominent example is preeclampsia, a hypertensive disease of
      pregnancy, characterized by the presence of autoantibodies that activate the
      major angiotensin receptor, AT(1). AT(1) receptor-activating autoantibodies are
      also observed in kidney transplant recipients suffering from severe vascular
      rejection and malignant hypertension. AT(1) receptor-activating autoantibodies
      and antibodies that activate the endothelin-1 receptor, ET(A), are prevalent in
      individuals diagnosed with systemic sclerosis. Thus, the presence of agonistic
      autoantibodies directed to G protein-coupled receptors has been observed in
      numerous cardiovascular disease states. Rapidly emerging evidence indicates that
      receptor-activating autoantibodies contribute to disease, and that efforts to
      detect and remove these pathogenic autoantibodies or block their actions will
      provide promising therapeutic possibilities.

PMID- 21895482
TI  - Quantitative relationship between axonal injury and mechanical response in a
      rodent head impact acceleration model.
AB  - A modified Marmarou impact acceleration model was developed to study the
      mechanical responses induced by this model and their correlation to traumatic
      axonal injury (TAI). Traumatic brain injury (TBI) was induced in 31 anesthetized
      male Sprague-Dawley rats (392+/-13 g) by a custom-made 450-g impactor from
      heights of 1.25 m or 2.25 m. An accelerometer and angular rate sensor measured
      the linear and angular responses of the head, while the impact event was captured
      by a high-speed video camera. TAI distribution along the rostro-caudal direction,
      as well as across the left and right hemispheres, was determined using beta
      amyloid precursor protein (beta-APP) immunocytochemistry, and detailed TAI injury
      maps were constructed for the entire corpus callosum. Peak linear acceleration
      1.25 m and 2.25 m impacts were 666+/-165 g and 907+/-501 g, respectively. Peak
      angular velocities were 95+/-24 rad/sec and 124+/-48 rad/sec, respectively.
      Compared to the 2.25-m group, the observed TAI counts in the 1.25-m impact group
      were significantly lower. Average linear acceleration, peak angular velocity,
      average angular acceleration, and surface righting time were also significantly
      different between the two groups. A positive correlation was observed between
      normalized total TAI counts and average linear acceleration (R(2)=0.612, p<0.05),
      and time to surface right (R(2)=0.545, p<0.05). Our study suggested that a 2.25-m
      drop in the Marmarou model may not always result in a severe injury, and TAI
      level is related to the linear and angular acceleration response of the rat head
      during impact, not necessarily the drop height.

PMID- 21895483
TI  - Cerebrovascular connexin expression: effects of traumatic brain injury.
AB  - Traumatic brain injury (TBI) results in dysfunction of the cerebrovasculature.
      Gap junctions coordinate vasomotor responses and evidence suggests that they are
      involved in cerebrovascular dysfunction after TBI. Gap junctions are comprised of
      connexin proteins (Cxs), of which Cx37, Cx40, Cx43, and Cx45 are expressed in
      vascular tissue. This study tests the hypothesis that TBI alters Cx mRNA and
      protein expression in cerebral vascular smooth muscle and endothelial cells.
      Anesthetized (1.5% isoflurane) male Sprague-Dawley rats received sham or fluid
      percussion TBI. Two, 6, and 24 h after, cerebral arteries were harvested, fresh
      frozen for RNA isolation, or homogenized for Western blot analysis. Cerebral
      vascular endothelial and smooth muscle cells were selected from frozen sections
      using laser capture microdissection. RNA was quantified by ribonuclease
      protection assay. The mRNA for all four Cx genes showed greater expression in the
      smooth muscle layer compared to the endothelial layer. Smooth muscle Cx43 mRNA
      expression was reduced 2  h and endothelial Cx45 mRNA expression was reduced 24 
      h after injury. Western blot analysis revealed that Cx40 protein expression
      increased, while Cx45 protein expression decreased 24  h after injury. These
      studies revealed significant changes in the mRNA and protein expression of
      specific vascular Cxs after TBI. This is the first demonstration of cell type
      related differential expression of Cx mRNA in cerebral arteries, and is a first
      step in evaluating the effects of TBI on gap junction communication in the
      cerebrovasculature.

PMID- 21895484
TI  - The impact of 5,10-methenyltetrahydrofolate synthetase polymorphism on diabetic
      nephropathy in the Taiwanese population.
AB  - Genome-wide association studies provide information implicating 5,10
      methenyltetrahydrofolate synthetase (MTHFS) as a candidate gene for renal
      disease. In the Atherosclerosis Risk in Communities study, the intronic single
      nucleotide polymorphism rs6495446 in the gene MTHFS confirmed the association
      between this gene and renal disease among Caucasian participants. We replicated
      this genetic association in a Taiwanese population with diabetic nephropathy
      (DN). A total of 358 Taiwanese patients with type 2 diabetes (T2D) were
      recruited. The case group comprised 180 T2D patients with DN, and the control
      group comprised the remaining patients without DN. rs6495446 in MTHFS had no
      significant effect on the risk of DN in Taiwanese patients with T2D. Multivariate
      logistic regression analysis demonstrated that being male, the duration of
      diabetes, plasma triglyceride level, and glycemic control were factors that
      predicted the development of DN.

PMID- 21895485
TI  - Braided nanofibrous scaffold for tendon and ligament tissue engineering.
AB  - Tendon and ligament (T/L) injuries present an important clinical challenge due to
      their intrinsically poor healing capacity. Natural healing typically leads to the
      formation of scar-like tissue possessing inferior mechanical properties.
      Therefore, tissue engineering has gained considerable attention as a promising
      alternative for T/L repair. In this study, we fabricated braided nanofibrous
      scaffolds (BNFSs) as a potential construct for T/L tissue engineering. Scaffolds
      were fabricated by braiding 3, 4, or 5 aligned bundles of electrospun poly(L
      lactic acid) nanofibers, thus introducing an additional degree of flexibility to
      alter the mechanical properties of individual scaffolds. We observed that the
      Young's modulus, yield stress, and ultimate stress were all increased in the 3
      bundle compared to the 4- and 5-bundle BNFSs. Interestingly, acellular BNFSs
      mimicked the normal tri-phasic mechanical behavior of native tendon and ligament
      (T/L) during loading. When cultured on the BNFSs, human mesenchymal stem cells
      (hMSCs) adhered, aligned parallel to the length of the nanofibers, and displayed
      a concomitant realignment of the actin cytoskeleton. In addition, the BNFSs
      supported hMSC proliferation and induced an upregulation in the expression of key
      pluripotency genes. When cultured on BNFSs in the presence of tenogenic growth
      factors and stimulated with cyclic tensile strain, hMSCs differentiated into the
      tenogenic lineage, evidenced most notably by the significant upregulation of
      Scleraxis gene expression. These results demonstrate that BNFSs provide a
      versatile scaffold capable of supporting both stem cell expansion and
      differentiation for T/L tissue engineering applications.

PMID- 21895487
TI  - Differences between chondrocytes and bone marrow-derived chondrogenic cells.
AB  - Implantation of autologous chondrogenic cells has become the mainstay strategy
      for repairing articular cartilage defects. Because the availability of autologous
      chondrocytes is extremely limited, many recent studies have used artificially
      induced mesenchymal stem cells (iMSCs) as substitutes for chondrocytes. In this
      study, we analyzed the differences between the iMSCs and chondrocytes, including
      their molecular biological and mechanical properties. Human bone marrow-derived
      MSCs were collected and induced to exhibit the chondrogenic phenotype by
      culturing the pelleted MSCs in a chemically defined culture medium supplemented
      with transforming growth factor-beta 1. The molecular biological properties of
      iMSCs and culture-expanded chondrocytes, including their mRNA profiles and
      surface proteomics, were analyzed using reverse transcription-polymerase chain
      reaction (RT-PCR) and flow cytometry, respectively. The biomechanical properties
      of iMSCs and native chondrocytes, including their surface topology, adhesion
      force, and membrane stiffness, were analyzed using atomic force microscopy (AFM).
      Both iMSCs and chondrocytes presented type II collagen and glycosaminoglycan,
      whereas only chondrocytes presented type X collagen. Flow cytometric assays
      showed that the expression of type II collagen and integrin-1 was higher in the
      chondrocytes than in the iMSCs. AFM revealed that the MSCs, iMSCs, and
      chondrocytes greatly differed in their shape. The MSCs were spindle shaped and
      easily distinguishable from the spherical chondrocytes. The iMSCs appeared round
      and resembled the spherical chondrocytes; however, the iMSCs were flatter with a
      central hump of condensed mass and a surrounding thin and broad pleat. The mean
      adhesion force and mean surface stiffness were significantly lower for the iMSCs
      (4.54 nN and 0.109 N/m, respectively) than for the chondrocytes (6.86 nN and
      0.134 N/m, respectively). To conclude, although the iMSCs exhibited the
      chondrogenic phenotype, they differed from the chondrocytes in their molecular
      biological and mechanical properties.

PMID- 21895486
TI  - Characterization of in vitro endothelial linings grown within microfluidic
      channels.
AB  - In vivo, endothelial cells grow on the inner surface of blood vessels and are
      shaped to conform to the vessel's geometry. In the smallest vessels this shape
      entails substantial bending within each cell. Microfabricated channels can
      replicate these small-scale geometries, but endothelial cells grown within them
      have not been fully characterized. In particular, the presence of focal adhesions
      and adherens junctions in endothelial cells grown in microchannels with corners
      has not been confirmed. We have fabricated square microfluidic channels (50 MUm
      wide, 50 MUm deep) and semicircular microfluidic channels (60 MUm wide, 45 MUm
      deep) in polydimethylsiloxane and cultured human umbilical vein endothelial cells
      (HUVEC) within them. Immunofluorescent staining and three-dimensional
      reconstruction of image stacks taken with confocal microscopy confirmed that
      HUVEC are capable of forming adherens junctions on all channel walls in both
      channel geometries, including the sidewalls of square profile channels. The
      presence of shear stress is critical for the cells to form focal adhesions within
      both channel geometries. Shear stress is also responsible for the conforming of
      HUVEC to the channel walls and produces a square cross-sectional geometry of in
      vitro endothelial linings within square profile channels. Thus, geometry and
      applied shear stress are important design criteria for the development of in
      vitro endothelial linings of microvessels.

PMID- 21895488
TI  - Sustaining neovascularization of a scaffold through staged release of vascular
      endothelial growth factor-A and platelet-derived growth factor-BB.
AB  - Tissue regeneration into a three-dimensional scaffold requires the stimulation of
      blood vessel ingrowth. We have employed a freely interconnecting porous scaffold
      developed by us to determine the utility of a covalently bound heparin surface
      coating for the delivery of vascular endothelial growth factor (VEGF) and
      platelet-derived growth factor BB (PDGF-BB) in vivo. The heparin surface was
      shown to release VEGF far more rapidly than PDGF-BB in vitro (VEGF: 75 ng/h for
      24 h; PDGF-BB: 86 pg/h for >7 days). In rat subcutaneous implants, at 10 days the
      heparin surface alone increased vessel ingrowth substantially (p<0.05 vs.
      unmodified scaffold), release of VEGF resulted in a further increase (p<0.05 vs.
      heparinized scaffold), whereas PDGF-BB had no additional effect. The increase
      induced by the combination of growth factors was similar to VEGF alone. After 2
      months, PDGF-BB, but not VEGF delivery, resulted in a substantial increase in
      vascularization above that induced by heparin (p<0.05). At the longer time point
      the combination of growth factors was similar to PDGF-BB. However, only the
      combination of growth factors significantly elevated the number of ingrowing
      arterioles (p<0.05 vs. heparinized scaffold). Thus, the covalent modification of
      a porous scaffold with heparin allows for the differential release of VEGF and
      PDGF-BB that results in both a rapid and sustained increase in scaffold
      vascularization.

PMID- 21895489
TI  - Depression scores associate with chronotype and social jetlag in a rural
      population.
AB  - In public health, mood disorders are among the most important mental impairments.
      Patients with depressive episodes exhibit daily mood variations, abnormal
      patterns in sleep-wake behavior, and in the daily rhythms of several endocrine
      metabolic parameters. Although the relationship between the sleep/circadian
      processes and mood disorders is poorly understood, clock-related therapies, such
      as light therapy, sleep deprivation, and rigid sleep schedules, have been shown
      to be effective treatments. Several studies investigated the relationship between
      circadian phenotype (chronotype) and depression. These focused mainly on urban
      populations and assessed diurnal preferences (Morningness-Eveningness score)
      rather than the actual timing of sleep and activity. Here, we used the Beck
      Depression Inventory (BDI) in an essentially rural population (N?=?4051), and
      investigated its relation to circadian phenotype (chronotype and social jetlag),
      assessed with the Munich Chronotype Questionnaire (MCTQ). In our study design, we
      (i) normalized both chronotype and BDI scores for age and sex (MSF(sas) and
      BDI(as), respectively); (ii) calculated individual social jetlag (misalignment of
      the biological and social time); and (iii) investigated the relationship between
      circadian phenotypes and BDI scores in a population homogeneous in respect to
      culture, socioeconomic factors, and daily light exposure. A 15.65% (N?=?634) of
      the participants showed mild to severe depressive BDI scores. Late chronotypes
      had a higher BDI(as) than intermediate and early types, which was independent of
      whether or not the participants were smokers. Both chronotype and BDI(as)
      correlated positively with social jetlag. BDI(as) was significantly higher in
      subjects with >2?h of social jetlag than in the rest of the population?again
      independent of smoking status. We also compared chronotype and social jetlag
      distributions between BDI categories (no symptoms, minimal symptoms, and mild to
      severe symptoms of depression) separately for men and women and for four age
      groups; specifically in the age group 31?40 yrs, subjects with mild to severe BDI
      scores were significantly later chronotypes and suffered from higher social
      jetlag. Our results indicate that misalignment of circadian and social time may
      be a risk factor for developing depression, especially in 31- to 40-yr-olds.
      These relationships should be further investigated in longitudinal studies to
      reveal if reduction of social jetlag should be part of prevention strategies.
      (Author correspondence:  karla.allebrandt@med.uni-muenchen.de ).

PMID- 21895490
TI  - Stocking density affects circadian rhythms of locomotor activity in African
      catfish, Clarias gariepinus.
AB  - The effect of stocking density on the locomotor activity of African catfish C.
      gariepinus under different light regimes was investigated. C. gariepinus were
      stocked under different densities (1, 5, or 10 fish/tank), and their locomotor
      activity recorded under light-dark (LD), constant light (LL), constant darkness
      (DD), and LD-reversed (DL) regimens. Under the LD cycle, catfish showed a
      crepuscular activity pattern, irrespective of stocking density, with most of the
      daily activity concentrated around the light-onset and light-offset times. When
      fish were subjected to DD, all 4 tanks with medium (5 fish) and high (10 fish)
      stocking densities showed circadian rhythmicity, with an average period (?) of
      23.3???0.5 and 24.6???0.5?h, respectively. In contrast, only 2 low (1 fish)
      density tanks showed free-running rhythms. Under LL, activity levels decreased
      significantly in comparison with levels observed under LD and DD. Moreover, fish
      of 1, 2, and 3 out of the 4 tanks with low, medium, and high densities,
      respectively, showed free-running rhythms under these conditions. When the
      photocycle was reversed (DL), fish of 3, 2, and 4 out of the 4 tanks with low,
      medium, and high stocking densities, respectively, showed gradual
      resynchronization to the new phase, and transient cycles of activity were
      observed. These results suggest that stocking density of fish affected the
      display of circadian rhythmicity and the intensity of activity levels. Thus, fish
      kept in higher densities showed more robust rhythmicity and higher levels of
      daily activity, indicating that social interactions may have an influence on
      behavioral patterns in the African catfish.

PMID- 21895492
TI  - Characterization and optimization of cell seeding in scaffolds by factorial
      design: quality by design approach for skeletal tissue engineering.
AB  - Cell seeding into scaffolds plays a crucial role in the development of efficient
      bone tissue engineering constructs. Hence, it becomes imperative to identify the
      key factors that quantitatively predict reproducible and efficient seeding
      protocols. In this study, the optimization of a cell seeding process was
      investigated using design of experiments (DOE) statistical methods. Five seeding
      factors (cell type, scaffold type, seeding volume, seeding density, and seeding
      time) were selected and investigated by means of two response parameters,
      critically related to the cell seeding process: cell seeding efficiency (CSE) and
      cell-specific viability (CSV). In addition, cell spatial distribution (CSD) was
      analyzed by Live/Dead staining assays. Analysis identified a number of
      statistically significant main factor effects and interactions. Among the five
      seeding factors, only seeding volume and seeding time significantly affected CSE
      and CSV. Also, cell and scaffold type were involved in the interactions with
      other seeding factors. Within the investigated ranges, optimal conditions in
      terms of CSV and CSD were obtained when seeding cells in a regular scaffold with
      an excess of medium. The results of this case study contribute to a better
      understanding and definition of optimal process parameters for cell seeding. A
      DOE strategy can identify and optimize critical process variables to reduce the
      variability and assists in determining which variables should be carefully
      controlled during good manufacturing practice production to enable a clinically
      relevant implant.

PMID- 21895491
TI  - Toward a clinical-grade expansion of mesenchymal stem cells from human sources: a
      microcarrier-based culture system under xeno-free conditions.
AB  - The immunomodulatory properties of mesenchymal stem cells (MSCs) make them
      attractive therapeutic agents for a wide range of diseases. However, the highly
      demanding cell doses used in MSC clinical trials (up to millions of cells/kg
      patient) currently require labor intensive methods and incur high reagent costs.
      Moreover, the use of xenogenic (xeno) serum-containing media represents a risk of
      contamination and raises safety concerns. Bioreactor systems in combination with
      novel xeno-free medium formulations represent a viable alternative to
      reproducibly achieve a safe and reliable MSC doses relevant for cell therapy. The
      main goal of the present study was to develop a complete xeno-free microcarrier
      based culture system for the efficient expansion of human MSC from two different
      sources, human bone marrow (BM), and adipose tissue. After 14 days of culture in
      spinner flasks, BM MSC reached a maximum cell density of (2.0+/-0.2)*105 cells.mL
      1 (18+/-1-fold increase), whereas adipose tissue-derived stem cells expanded to
      (1.4+/-0.5)*105 cells.mL-1 (14+/-7-fold increase). After the expansion, MSC
      expressed the characteristic markers CD73, CD90, and CD105, whereas negative for
      CD80 and human leukocyte antigen (HLA)-DR. Expanded cells maintained the ability
      to differentiate robustly into osteoblast, adipocyte, and chondroblast lineages
      upon directed differentiation. These results demonstrated the feasibility of
      expanding human MSC in a scalable microcarrier-based stirred culture system under
      xeno-free conditions and represent an important step forward for the
      implementation of a Good Manufacturing Practices-compliant large-scale production
      system of MSC for cellular therapy.

PMID- 21895493
TI  - Formation of an aggregated alginate construct in a tubular perfusion system.
AB  - Tissue engineering strategies are often limited by in vitro culture techniques of
      three dimensional scaffolds. Here we develop a method to form an aggregated cell
      containing construct in vitro in a bioreactor system. Human mesenchymal stem
      cells (hMSCs) are cultured in individual alginate beads in a tubular perfusion
      system (TPS) bioreactor and then aggregated to form a single large construct.
      Mechanical evaluation of this construct demonstrated that aggregated alginate
      constructs (AACs) made from beads with 2.15 mm diameters had a Young's modulus of
      85.6+/-15.8 kPa, a tensile strength of 3.24+/-0.55 kPa and a yield strength of
      1.44+/-0.27 kPa. These mechanical properties were shown to be dependent on the
      bead size used to fabricate the AACs with smaller bead sizes resulting in
      stronger constructs. Analysis of metabolic activity revealed that hMSCs
      encapsulated in alginate exposed to AAC treatment sustained metabolic activity
      while live dead staining indicated cells remain viable. These results demonstrate
      the formation of AACs in the TPS bioreactor as an elegant method to create tissue
      engineering constructs in vitro.

PMID- 21895494
TI  - Three-dimensional system for the in vitro study of megakaryocytes and functional
      platelet production using silk-based vascular tubes.
AB  - Platelets are specialized cells produced by megakaryocytes in the bone marrow
      that represent the first defense against hemorrhage, yet they also play a
      pathological role in thrombosis, inflammation, and cancer. Millions of platelet
      transfusions are conducted each year, and the supply of this blood component is
      limited. There are many diseases where platelet production or function is
      impaired with severe consequences for patients. With such clinical need, new
      insight into the formation of platelets would have a major impact on patients and
      healthcare. We developed an innovative 3D system to study platelet production
      that represents the first spatial reconstruction of the bone marrow environment.
      In this system human megakaryocytes were able to migrate toward the vascular
      niche, extend proplatelets, and release functional platelets into vascular tubes.
      The combination of different bone marrow components and the compliance of silk
      based vascular tubes makes this model a unique tool for the study of platelet
      formation and production for use in healthcare needs.

PMID- 21895495
TI  - Bone tissue engineering in oral surgery: a new method of bone development in
      periodontal surgery.
AB  - This article describes the development of a new surgical approach to periodontal
      treatment. Twenty patients who suffered from bone defects without existing bony
      walls due to adult periodontitis were treated in three different groups using
      methods of bone tissue engineering. At that time no surgical technique existed
      that could be applied to those patients to generate new bone. The periodontal
      surgeries were performed between 2004 and 2008. All patients received follow-up
      examinations at 6, 12, and 24 months after surgical procedure. Measured
      parameters were compared to baseline. The surgical approach and the augmentation
      material have been improved based on the results of the previous group. This
      strategy was applied because of the ethical fact that a medical treatment of
      patients has to be carried out with the knowledge and experience of previous
      settings. All groups received recombinant human bone morphogenetic protein 2 and
      platelet-rich plasma. The above-mentioned procedure had been approved in other
      indications in the field of oral and maxillofacial surgery. The first group
      underwent conventional muco-periosteal flap technique and obtained an
      augmentation with absorbable collagen sponge (ACS). The second and third groups
      were treated using endoscopically assisted microsurgery due to wound healing
      disturbances that appeared in the first group. The augmentation was carried out
      with demineralized bone matrix (DBM) instead of ACS (group 2) or
      tricalciumphosphate as a further development instead of DBM (group 3). The
      radiological control 12 months (group 1), 18 months (group 2), and 2 years (group
      3) after surgery proved the following results-first group: 1.7 mm (average)
      vertical bone development (VBD); second group: 2.5 mm (average) VBD; third group:
      3.2 mm (average) VBD. These results of single patient treatment open new ways
      into periodontal surgery. They have to be confirmed by prospective case series
      and multicenter studies.

PMID- 21895496
TI  - Effects of poly(amidoamine) dendrimers on ocular absorption of puerarin using
      microdialysis.
AB  - PURPOSE: The purpose of this study was to investigate the effects of
      poly(amidoamine) (PAMAM) dendrimers on ocular absorption of puerarin. METHODS:
      The samples of rabbits' aqueous humor were collected by in vivo microdialysis.
      The ocular pharmacokinetic properties of puerarin were measured to evaluate the
      effects of PAMAM dendrimers on ocular absorption of puerarin. RESULTS: In the
      pharmacokinetic studies, the AUC(0~infinity) values of puerarin solution with
      0.2% (w/v) PAMAM dendrimers (G3.0, G4.0, G5.0) were greater than those in the
      control group by 2.3-, 3.5-, and 2.1-folds, respectively. The C(max) values of
      puerarin solution with 0.2% (w/v) PAMAM dendrimers were 1.5, 2.5, and 1.3 times
      the values of the control group and the t(1/2) values were significantly longer
      than that of control group. CONCLUSIONS: Using PAMAM dendrimers might be a
      promising strategy to enhance the absorption of puerarin. The generation of PAMAM
      dendrimers may play a key role in increasing the ocular absorption of puerarin.

PMID- 21895497
TI  - Strontium doping of bone graft extender.
AB  - BACKGROUND AND PURPOSE: Allografts are often used during revision hip replacement
      surgery for stabilization of the implant. Resorption of the allograft may exceed
      new bone formation, and instability of the prosthesis can develop. We
      investigated whether strontium could regulate the imbalance of fast resorption of
      allograft and slower formation of new bone, because it is both an anabolic and an
      anticatabolic agent. METHOD: Strontium was added to the implant interface
      environment by doping a hydroxyapatite bone graft extender. 10 dogs each received
      2 experimental titanium implants. The implants were inserted within a 2.7-mm
      concentric gap in cancellous bone. The gap was filled with 50% (v/v) allograft
      mixed with 50% bone graft extender. The extender either had 5% strontium doping
      (SrHA) or was undoped (HA). After 4 weeks, osseointegration and mechanical
      fixation were evaluated by histomorphometry and by push-out test. RESULTS: SrHA
      bone graft extender induced a 1.2-fold increase in volume of new bone, a 1.2-fold
      increase in allograft remaining in the gap, and a 1.4-fold increase in surface
      area of the bone graft extender material in contact with new bone compared to HA
      bone graft extender. All these increases were statistically significant. SrHA
      bone graft extender did not significantly improve ongrowth of bone onto the
      implants or improve any of the mechanical push-out parameters compared to HA bone
      graft extender. INTERPRETATION: Doping of the HA bone graft extender with 5%
      strontium increased gap healing, preserved more of the allograft in the gap, and
      increased the ongrowth of bone onto the bone graft extender material, but did not
      improve mechanical fixation.

PMID- 21895498
TI  - Complications after hip arthroplasty and the association with hospital procedure
      volume.
AB  - BACKGROUND AND PURPOSE: It has been suggested that a higher procedure volume is
      associated with less complications after hip arthroplasty. In order to
      investigate the incidence of serious negative outcomes and a possible association
      with procedure volume, we performed a retrospective nationwide cohort study on
      total hip replacements in all Dutch hospitals. METHODS: All total hip
      replacements (n = 50,080) that were identified as primary intervention in all
      general and university medical centers between January 1, 2002 and October 1,
      2004 were included. Primary endpoints of follow-up were mortality and
      complications during admission, and re-admission within 3 months due to
      complications. Variables that were assessed as potential risk factor were age,
      sex, duration of (preoperative) admission, specific diagnosis, acute/non-planned
      admission, co-morbidity, and hospital procedure volume. RESULTS: Age, sex, and
      comorbidity were associated with complications and mortality. Additionally, acute
      admission was a risk factor for mortality but not for complications. There was no
      linear trend indicating that decreasing volume led to an increasing number of
      complications, and no statistically sginificant effect for mortality was found.
      INTERPRETATION: After adjustment for several risk factors, we found that the
      hospitals performing most hip procedures every year had fewer complications
      during index admission, but that they did not have a lower mortality than groups
      performing fewer procedures. The lack of a linear trend may be explained by the
      fact that almost all Dutch hospitals perform a high number of hip arthroplasties
      each year.

PMID- 21895499
TI  - Preoperative lateral subluxation of the patella is a predictor of poor early
      outcome of Oxford phase-III medial unicompartmental knee arthroplasty.
AB  - BACKGROUND AND PURPOSE: There is disagreement in the literature about the
      importance of patellofemoral joint degeneration and knee pain for the outcome of
      unicompartmental knee arthroplasty (UKA). We therefore investigated the
      importance of selected predictors including patellofemoral joint degeneration and
      the location of preoperative knee pain for the early outcome of UKA. PATIENTS AND
      METHODS: The study group comprised 260 consecutive patients from 5 hospitals who
      underwent Oxford UKA for anteromedial osteoarthritis. Data were collected at
      baseline and included pain location, radiologically observed degeneration of the
      patellofemoral joint including subluxation of the patella, intraoperative
      cartilage status of the patellofemoral joint, disease-specific knee status, and
      Oxford knee score (OKS). Outcomes were evaluated after 1 year using the OKS,
      global patient satisfaction, and global patient result. RESULTS: The average OKS
      score at baseline was 24 (SD 7), and it was 40 (SD 8) at the 1-year follow-up.
      94% of the patients claimed improvement after the operation and 90% were
      satisfied with the UKA. Lateral subluxation of the patella was a predictor of
      poor outcome, and the preoperative OKS score was also a predictor of outcome.
      Full-thickness cartilage loss at any location gave a similar outcome to that with
      a normal or near-normal joint surface, and likewise, preoperative anterior knee
      pain was not a predictor of outcome. INTERPRETATION: We conclude that the good
      early outcome after UKA in this study is in line with the best reported results.
      Patellofemoral degeneration should not be considered a contraindication to Oxford
      UKA. Patients with lateral subluxation of the patella have an increased risk of a
      poor result after UKA and should preferably be offered a total knee replacement.

PMID- 21895500
TI  - Enhanced recovery program for hip and knee replacement reduces death rate.
AB  - BACKGROUND AND PURPOSE: Multimodal techniques can aid early rehabilitation and
      discharge of patients following primary joint replacement. We hypothesized that
      this not only reduces the economic burden of joint replacement by reducing length
      of stay, but also helps in reduction of early complications. PATIENTS AND
      METHODS: We evaluated 4,500 consecutive unselected total hip replacements and
      total knee replacements regarding length of hospital stay, mortality, and
      perioperative complications. The first 3,000 underwent a traditional protocol
      while the other 1,500 underwent an enhanced recovery protocol involving
      behavioral, pharmacological, and procedural modifications. RESULTS: There was a
      reduction in 30-day death rate (0.5% to 0.1%, p = 0.02) and 90-day death rate
      (0.8% to 0.2%, p = 0.01). The median length of stay decreased from 6 days to 3
      days (p < 0.001), resulting in a saving of 5,418 bed days. Requirement for blood
      transfusion was reduced (23% to 9.8%, p < 0.001). There was a trend of a reduced
      rate of 30-day myocardial infarction (0.8% to 0.5%. p = 0 .2) and stroke (0.5% to
      0.2%, p = 0.2). The 60-day deep vein thrombosis figures (0.8% to 0.6%, p = 0.5)
      and pulmonary embolism figures (1.2% to 1.1%, p = 0.9) were similar. Re-admission
      rate remained unchanged during the period of the study (4.7% to 4.8%, p = 0.8).
      INTERPRETATION: This large observational study of unselected consecutive hip and
      knee arthroplasty patients shows a substantial reduction in death rate, reduced
      length of stay, and reduced transfusion requirements after the introduction of a
      multimodal enhanced recovery protocol.

PMID- 21895501
TI  - Modulation of the intramedullary pressure responses by calcium dobesilate in a
      rabbit knee model of osteoarthritis.
AB  - BACKGROUND AND PURPOSE: The presence of bone marrow edema in patients with
      osteoarthritis is associated with pain and disease progression. Management of
      bone edema with the synthetic prostacyclin iloprost may be complicated by side
      effects. Calcium dobesilate, a treatment for chronic venous disease, shares some
      pharmacological actions with iloprost but appears to be better tolerated.
      Anecdotal reports have suggested that calcium dobesilate may be useful for
      medical management of osteoarthritis, possibly by reducing bone marrow edema, and
      this study was performed to investigate possible benefits of treatment. METHODS:
      The effects of a 6-week period of oral calcium dobesilate administration on
      tibial intramedullary pressure dynamics and physical joint characteristics were
      evaluated in 20 rabbits with unilaterally induced knee osteoarthritis that were
      randomly allocated to either a treatment group or a placebo control group.
      Treatment or placebo started 8 weeks after induction of osteoarthritis, and was
      followed by a 4-week washout period. RESULTS: Calcium dobesilate did not affect
      joint thickness or range of motion, nor individual pressure measurements,
      compared to placebo. Pressure ranges in the operated limb were greater than in
      the intact limb after 8 weeks, and approached those of the intact limb after 6
      weeks of treatment with calcium dobesilate but not with placebo. Inter-limb
      differences were lower (p = 0.02) in the dobesilate group following the washout
      period. INTERPRETATION: Calcium dobesilate had a detectable effect on pressure
      dynamics in the subchondral bone of osteoarthritic joints in this model. The
      significance of these effects for pain and function should be established.

PMID- 21895502
TI  - Isolated fractures of the greater tuberosity of the proximal humerus: a long-term
      retrospective study of 30 patients .
AB  - BACKGROUND AND PURPOSE: The diagnosis and treatment of isolated greater
      tuberosity fractures of the proximal humerus is not clear-cut. We retrospectively
      assessed the clinical and radiographic outcome of isolated greater tuberosity
      fractures. PATIENTS AND METHODS: 30 patients (mean age 58 (26-85) years, 19
      women) with 30 closed isolated greater tuberosity fractures were reassessed after
      an average follow-up time of 3 years with DASH score and Constant score.
      Radiographic outcome was assessed on standard plain radiographs. RESULTS: 14 of
      17 patients with undisplaced or slightly displaced fractures (<= 5 mm) were
      treated nonoperatively and had good clinical outcome (mean DASH score of 13, mean
      Constant score of 71). 8 patients with moderately displaced fractures (6-10 mm)
      were either treated nonoperatively (n = 4) or operatively (n = 4), with good
      functional results (mean DASH score of 10, mean Constant score of 72). 5 patients
      with major displaced fractures (> 10 mm) were all operated with good clinical
      results (mean DASH score of 14, mean Constant score of 69). The most common
      discomfort at the follow-up was an impingement syndrome of the shoulder, which
      occurred in both nonoperatively treated patients (n = 3) and operatively treated
      patients (n = 4). Only 1 nonoperatively treated patient developed a non-union. By
      radiography, all other fractures healed. INTERPRETATION: We found that minor to
      moderately displaced greater tuberosity fractures may be treated successfully
      without surgery.

PMID- 21895503
TI  - Metal-backed versus all-polyethylene tibial components in primary total knee
      arthroplasty.
AB  - BACKGROUND AND PURPOSE: The choice of either all-polyethylene (AP) tibial
      components or metal-backed (MB) tibial components in total knee arthroplasty
      (TKA) remains controversial. We therefore performed a meta-analysis and
      systematic review of randomized controlled trials that have evaluated MB and AP
      tibial components in primary TKA. METHODS: The search strategy included a
      computerized literature search (Medline, EMBASE, Scopus, and the Cochrane Central
      Register of Controlled Trials) and a manual search of major orthopedic journals.
      A meta-analysis and systematic review of randomized or quasi-randomized trials
      that compared the performance of tibial components in primary TKA was performed
      using a fixed or random effects model. We assessed the methodological quality of
      studies using Detsky quality scale. RESULTS: 9 randomized controlled trials
      (RCTs) published between 2000 and 2009 met the inclusion quality standards for
      the systematic review. The mean standardized Detsky score was 14 (SD 3). We found
      that the frequency of radiolucent lines in the MB group was significantly higher
      than that in the AP group. There were no statistically significant differences
      between the MB and AP tibial components regarding component positioning, knee
      score, knee range of motion, quality of life, and postoperative complications.
      INTERPRETATION: Based on evidence obtained from this study, the AP tibial
      component was comparable with or better than the MB tibial component in TKA.
      However, high-quality RCTs are required to validate the results.

PMID- 21895504
TI  - A randomized study on migration of the Spectron EF and the Charnley flanged 40
      cemented femoral components using radiostereometric analysis at 2 years.
AB  - BACKGROUND AND PURPOSE: We performed a randomized study to determine the
      migration patterns of the Spectron EF femoral stem and to compare them with those
      of the Charnley stem, which is regarded by many as the gold standard for
      comparison of implants due to its extensive documentation. PATIENTS AND METHODS:
      150 patients with a mean age of 70 years were randomized, single-blinded, to
      receive either a cemented Charnley flanged 40 monoblock, stainless steel,
      vaquasheen surface femoral stem with a 22.2-mm head (n = 30) or a cemented
      Spectron EF modular, matte, straight, collared, cobalt-chrome femoral stem with a
      28-mm femoral head and a roughened proximal third of the stem (n = 120). The
      patients were followed with repeated radiostereometric analysis for 2 years to
      assess migration. RESULTS: At 2 years, stem retroversion was 2.3 degrees  and 0.7
      degrees  (p < 0.001) and posterior translation was 0.44 mm and 0.17 mm (p =
      0.002) for the Charnley group (n = 26) and the Spectron EF group (n = 74),
      respectively. Subsidence was 0.26 mm for the Charnley and 0.20 mm for the
      Spectron EF (p = 0.5). INTERPRETATION: The Spectron EF femoral stem was more
      stable than the Charnley flanged 40 stem in our study when evaluated at 2 years.
      In a report from the Norwegian arthroplasty register, the Spectron EF stem had a
      higher revision rate due to aseptic loosening beyond 5 years than the Charnley.
      Initial stability is not invariably related to good long-term results. Our
      results emphasize the importance of prospective long-term follow-up of prosthetic
      implants in clinical trials and national registries and a stepwise introduction
      of implants.

PMID- 21895505
TI  - External or internal fixation in the treatment of non-reducible distal radial
      fractures?
AB  - BACKGROUND AND PURPOSE: We have previously shown in a randomized study that in
      the first year after treatment, open reduction and internal fixation resulted in
      better grip strength and forearm rotation than closed reduction and bridging
      external fixation. In the present study, we investigated whether this difference
      persists over time. PATIENTS AND METHODS: The 50 patients included in the
      original study (mean age 53 years, 36 women) were sent a QuickDASH questionnaire
      and an invitation to a radiographic and clinical examination after a mean of 5 (3
      7) years. RESULTS: All 50 patients returned the QuickDASH questionnaire and 45
      participated in the clinical and radiographic examination. In the internal
      fixation group, the grip strength was 95% (SD 12) of the uninjured side and in
      the external fixation group it was 90% (SD 21) of the uninjured side (p = 0.3).
      QuickDASH score, range of motion, and radiographic parameters were similar
      between the groups. INTERPRETATION: The difference originally found between
      internal and external fixation in distal radial fractures at 1 year regarding
      grip strength and range of motion was found to diminish with time. At 5 years,
      both groups had approached normal values.

PMID- 21895506
TI  - Genetic epidemiology of Scheuermann's disease.
AB  - BACKGROUND AND PURPOSE: The genetic/environmental etiology of Scheuermann's
      disease is unclear. We estimated the heritability of the disease using an
      etiological model adjusted for sex and time of diagnosis, and examined whether
      the prevalence of Scheuermann's disease was constant over time. METHODS: 46,418
      twins were sent a questionnaire about health and disease. Of these, 75% returned
      the questionnaire and 97% answered the question "Have you been diagnosed as
      having Scheuermann's disease by a doctor?" RESULTS: Responders included 11,436
      complete pairs of twins. Data were analysed using classical twin modeling
      methods. Tetrachoric correlations were used to decide which etiological model to
      fit. The best-fitting model was the AE model. Heritability was 0.74 (95% CI: 0.65
      0.81), while variance explained by environmental factors was 0.26 (95% CI: 0.19
      0.35). A threshold of 2.1 (95% CI: 1.9-2.2) was calculated, corresponding to a
      prevalence of 1.9% (95% CI: 1.3-2.8) for women. Regression coefficients for age
      and sex were 0.000 (95% CI: -0.003 to 0.002) and -0.32 (95% CI: -0.42 to -0.23).
      INTERPRETATION: We found a heritability of 0.74 in Scheuermann's disease. The
      threshold in men was lower than in women, corresponding to a male prevalence that
      was almost twice that of females. We found no change in the prevalence of
      Scheuermann's disease throughout the 50-year age span that we examined.

PMID- 21895507
TI  - Spasticity of the gastrosoleus muscle is related to the development of reduced
      passive dorsiflexion of the ankle in children with cerebral palsy: a registry
      analysis of 2,796 examinations in 355 children.
AB  - BACKGROUND AND PURPOSE: Spasticity and muscle contracture are two common
      manifestations of cerebral palsy (CP). A spastic muscle may inhibit growth in
      length of the muscle, but the importance of this relationship is not known. In
      1994, a register and a healthcare program for children with CP in southern Sweden
      were initiated. The child's muscle tone according to the Ashworth scale and the
      ankle range of motion (ROM) is measured annually during the entire growth period.
      We have used these data to analyze the relationship between spasticity and ROM of
      the gastrosoleus muscle. PATIENTS AND METHODS: All measurements in the total
      population of children with CP aged 0-18 years during the period January 1995
      through June 2008 were analyzed. The study was based on 2,796 examinations in 355
      children. In the statistical analysis, the effect of muscle tone on ROM was
      estimated using a random effects model. RESULTS: The range of dorsiflexion of the
      ankle joint decreased in the total material by mean 19 (95% CI: 14-24) degrees
      during the first 18 years of life. There was a statistically significant
      association between the ROM and the child's level of spasticity during the year
      preceding the ROM measurement. INTERPRETATION: Spasticity is related to the
      development of muscle contracture. In the treatment of children with CP, the
      spasticity, contracture, and strength of the gastrosoleus muscle must be
      considered together.

PMID- 21895508
TI  - Different competing risks models applied to data from the Australian Orthopaedic
      Association National Joint Replacement Registry.
AB  - PURPOSE: Here we describe some available statistical models and illustrate their
      use for analysis of arthroplasty registry data in the presence of the competing
      risk of death, when the influence of covariates on the revision rate may be
      different to the influence on the probability (that is, risk) of the occurrence
      of revision. PATIENTS AND METHODS: Records of 12,525 patients aged 75-84 years
      who had received hemiarthroplasty for fractured neck of femur were obtained from
      the Australian Orthopaedic Association National Joint Replacement Registry. The
      covariates whose effects we investigated were: age, sex, type of prosthesis, and
      type of fixation (cementless or cemented). Extensions of competing risk
      regression models were implemented, allowing the effects of some covariates to
      vary with time. RESULTS: The revision rate was significantly higher for patients
      with unipolar than bipolar prostheses (HR = 1.38, 95% CI: 1.01-1.89) or with
      monoblock than bipolar prostheses (HR = 1.45, 95% CI: 1.08-1.94). It was
      significantly higher for the younger age group (75-79 years) than for the older
      one (80-84 years) (HR = 1.28, 95% CI: 1.05-1.56) and higher for males than for
      females (HR = 1.37, 95% CI: 1.09-1.71). The probability of revision, after
      correction for the competing risk of death, was only significantly higher for
      unipolar prostheses than for bipolar prostheses, and higher for the younger age
      group. The effect of fixation type varied with time; initially, there was a
      higher probability of revision for cementless prostheses than for cemented
      prostheses, which disappeared after approximately 1.5 years. INTERPRETATION: When
      accounting for the competing risk of death, the covariates type of prosthesis and
      sex influenced the rate of revision differently to the probability of revision.
      We advocate the use of appropriate analysis tools in the presence of competing
      risks and when covariates have time-dependent effects.

PMID- 21895509
TI  - Cognitive screening in patients with amyotrophic lateral sclerosis in early
      stages.
AB  - Few studies have examined the use of a short cognitive screening of ALS patients
      in order to establish which patients should undergo a more comprehensive
      neuropsychological assessment. We tested 20 patients with early ALS with four
      cognitive screening instruments and subsequently with an extensive
      neuropsychological assessment. Sixty percent of patients showed a deficit in at
      least two scores of tests administered, while 40% had three abnormal tests.
      Dysexecutive syndrome was the most common neuropsychological impairment. The
      Frontal Assessment Battery (FAB) proved a useful indicator of the presence of
      cognitive dysfunction to complete neuropsychological evaluation. In conclusion,
      the FAB can be considered a sensitive cognitive screening tool in these patients.
      These data will be verified on a larger sample of patients.

PMID- 21895510
TI  - Escaping the cut by restriction enzymes through single-strand self-annealing of
      host-edited 12-bp and longer synthetic palindromes.
AB  - Palindromati, the massive host-edited synthetic palindromic contamination found
      in GenBank, is illustrated and exemplified. Millions of contaminated sequences
      with portions or tandems of such portions derived from the ZAP adaptor or related
      linkers are shown (1) by the 12-bp sequence reported elsewhere, exon Xb, 5'
      CCCGAATTCGGG 3', (2) by a 22-bp related sequence 5' CTCGTGCCGAATTCGGCACGAG 3',
      and (3) by a longer 44-bp related sequence: 5'
      CTCGTGCCGAATTCGGCACGAGCTCGTGCCGAATTCGGCACGAG 3'. Possible reasons for why those
      long contaminating sequences continue in the databases are presented here: (1)
      the recognition site for the plus strand (+) is single-strand self-annealed; (2)
      the recognition site for the minus strand (-) is not only single-strand self
      annealed but also located far away from the single-strand self-annealed plus
      strand, rendering impossible the formation of the active EcoRI enzyme dimer to
      cut on 5' G/AATTC 3', its target sequence. As a possible solution, it is
      suggested to rely on at least two or three independent results, such as sequences
      obtained by independent laboratories with the use, preferably, of independent
      sequencing methodologies. This information may help to develop tools for
      bioinformatics capable to detect/remove these contaminants and to infer why some
      damaged sequences which cause genetic diseases escape detection by the molecular
      quality control mechanism of cells and organisms, being undesirably transferred
      unchecked through the generations.

PMID- 21895513
TI  - The association between maternal alcohol use and smoking in early pregnancy and
      congenital cardiac defects.
AB  - BACKGROUND: Alcohol use is an extremely prevalent but preventable risk factor
      among women seeking to become pregnant. Many women continue to use alcohol in the
      early stages of pregnancy before they are aware they are pregnant. Research is
      unclear about the role of maternal alcohol use during pregnancy and congenital
      cardiac defects, one of the leading types of birth defects in the United States.
      METHODS: Data from the Pregnancy Risk Assessment Monitoring Survey (PRAMS) were
      used to examine maternal alcohol use and its association with congenital cardiac
      defects. Various measures of alcohol use in the 3 months prior to pregnancy, as
      well as smoking and other risk factors for congenital cardiac defects, were
      linked to birth certificate data for nine states over a 10-year period (1996
      2005). In this case-control study, cases included infants with a congenital
      cardiac defect indicated on the birth certificate, and the control group
      consisted of healthy, normal weight infants with no indication of a congenital
      abnormality on their birth certificate. Complex samples logistic regression
      models were used to study the relationships between several measures of alcohol
      use, including binge drinking and binge drinking on more than once occasion, and
      the interaction between alcohol use and smoking with the odds of congenital
      cardiac defects. RESULTS: A significant increase in congenital cardiac defects
      was found among mothers who reported binge drinking more than once in the 3
      months prior to pregnancy compared to mothers who did not report binge drinking
      (adjusted odds ratio [aOR] 2.99, 95% confidence interval [CI] 1.19-7.51). There
      was a significant interaction between any binge drinking or binge drinking more
      than once and cigarette use, which corresponded to a substancial increase in
      congenital cardiac defects (aOR 12.65, 95% CI 3.54-45.25 and aOR 9.45, 95% CI
      2.53-35.31, respectively). CONCLUSIONS: Multiple episodes of maternal binge
      drinking in early pregnancy may increase the odds of congenital cardiac defects,
      and we found this relationship was more dramatic when combined with maternal
      smoking.

PMID- 21895511
TI  - Macrophage colony stimulating factor regulation by nuclear factor kappa B: a
      relevant pathway in human immunodeficiency virus type 1 infected macrophages.
AB  - Macrophage colony stimulating factor (M-CSF) is a cytokine that promotes monocyte
      differentiation and survival. When overexpressed, M-CSF contributes to pathology
      in a wide variety of diseases, including osteoporosis, obesity, certain human
      cancers, and in human immunodeficiency virus type 1 (HIV-1) infection,
      particularly with respect to monocyte/macrophage infection and the development of
      HIV-1 associated central nervous system disorders. In this study, our aim was to
      expand the current knowledge of M-CSF regulation, focusing on nuclear factor
      kappa B (NF-kappaB), a transcription factor playing a prominent role during
      inflammation and HIV-1 infection. Our results suggest that tumor necrosis factor
      alpha (TNF-alpha) promotes M-CSF secretion in primary macrophages and activates
      the -1310/+48 bp M-CSF promoter in Mono-Mac 1 cells. Inhibitors of the NF-kappaB
      pathway diminish this response. We identified four putative NF-kappaB and four
      CCAAT-enhancer-binding protein beta binding sites within the M-CSF promoter. Our
      findings, using promoter constructs mutated at individual NF-kappaB sites within
      the M-CSF promoter region, suggest that these sites are redundant with respect to
      NF-kappaB regulation. TNF-alpha treatment promoted NF-kappaB p65 binding to the M
      CSF promoter in phorbol 12-myristate 13-acetate (PMA) treated U937 cells
      chronically infected with HIV-1 (U1 cells), but not in PMA treated uninfected
      U937 cells, suggesting that the presence of HIV-1 increases the NF-kappaB
      response. In conclusion, our findings demonstrate that NF-kappaB induces M-CSF
      expression on a promoter level via multiple functional NF-kappaB binding sites
      and that this pathway is likely relevant in HIV-1 infection of macrophages.

PMID- 21895514
TI  - Bilateral rubeosis iridis and rubeotic glaucoma due to peripheral occlusive
      vasculitis associated with multiple sclerosis.
AB  - Multiple sclerosis is associated with iridocyclitis, intermediate uveitis,
      retinal periphlebitis, and optic neuritis. The periphlebitis is known to be
      rarely sight-threatening as a result of the sequelae of retinal
      neovascularization. CASE: This is a rare case of bilateral rubeosis iridis and
      rubeotic glaucoma in the setting of a branch retinal vein occlusion, widespread
      peripheral periphlebitis, and angiographic peripheral closure associated with
      "clinically definite" multiple sclerosis. DISCUSSION: The case illustrates the
      extreme end of the spectrum of peripheral retinal ischemia and neovascularization
      associated with demyelinating disease, which can present as rubeotic glaucoma.
      Such patients require a proactive approach to inflammation, neovascularization,
      and raised intraocular pressure, including systemic immunosuppression,
      photocoagulation, and augmented trabeculectomy, respectively. As with other
      causes of peripheral ischemia, a favorable visual outcome can often be achieved
      using this strategy.

PMID- 21895515
TI  - Screening for vigabatrin (Sabril (r)) retinal toxicity in children.

PMID- 21895516
TI  - Physical activity patterns in patients in different stages of chronic obstructive
      pulmonary disease.
AB  - It has previously been suggested that exercise capacity is decreased in COPD and
      that it is associated with degree of disease. The reduced exercise capacity may
      plausibly be due to low levels of physical activity in this patient group. The
      aim of the present study was to assess exercise capacity and physical activity in
      different stages of COPD and to examine the associations between exercise
      capacity, pulmonary function and degree of physical activity. A total of 44 COPD
      patients and 17 healthy subjects participated in the study. Exercise capacity was
      assessed using the 6-minute walking test and physical activity was assessed using
      an accelerometer worn all waking hours during 7 days. Mean exercise capacity was
      significantly lower in COPD patients compared with healthy subjects. Mean
      physical activity level and time spent at least moderately active were
      significantly lower in patients with moderate and severe COPD compared with
      healthy subjects while no differences in time spent sedentary were observed
      between the study groups. Pulmonary function, mean physical activity level and
      time spent at least moderately physically active were significantly associated
      with exercise capacity in the patients. We conclude that patients with moderate
      and severe COPD are less physically active compared with healthy subjects.
      Furthermore, mean physical activity level and physical activity of at least
      moderate intensity are positively associated with exercise capacity in COPD,
      while time spent sedentary is not, which stresses an important role of physical
      activity on exercise capacity in these patients.

PMID- 21895517
TI  - Drugs on the Internet, part II: antidepressant medication web sites.
AB  - Antidepressant medications have been the fastest growing category of use of
      pharmaceutical products over the past decade. Selected Internet web sites
      providing information on antidepressant medications were identified and assessed
      using code of conduct criteria for posting health information on the Internet as
      developed by the Health on the Internet Foundation. Thirteen representative web
      sites were evaluated. Degree of compliance with each of the eight criterion
      varied by site, though all 13 sites met the criterion for legality of content and
      conduct on their web site. WebMD and FamilyDoctor.org met most of the criteria,
      while pharmaceutical company sites tended to meet the fewest criteria.

PMID- 21895518
TI  - Continuous monitoring of the Monro-Kellie doctrine: is it possible?
AB  - The Monro-Kellie doctrine describes the principle of homeostatic intracerebral
      volume regulation, which stipulates that the total volume of the parenchyma,
      cerebrospinal fluid, and blood remains constant. Hypothetically, a slow shift
      (e.g., brain edema development) in the irregular vasomotion-driven exchanges of
      these compartmental volumes may lead to increased intracranial hypertension. To
      evaluate this paradigm in a clinical setting and measure the processes involved
      in the regulation of systemic intracranial volume, we quantified cerebral blood
      flow velocity (CBFv) in the middle cerebral artery, arterial blood pressure
      (ABP), and intracranial pressure (ICP), in 238 brain-injured subjects. Relative
      changes in compartmental compliances C(a) (arterial) and C(i) (combined venous
      and CSF compartments) were mathematically estimated using these raw signals
      through time series analysis; C(a) and C(i) were used to compute an index of
      cerebral compliance (ICC) as a moving correlation coefficient between C(a) and
      C(i). Conceptually, a negative ICC would represent a functional Monro-Kellie
      doctrine by illustrating volumetric compensations between C(a) and C(i). Clinical
      observations show that Lundberg A-waves and arterial hypertension were associated
      with negative ICC, whereas in refractory intracranial hypertension, a positive
      ICC was observed. In subjects who died, ICC was significantly greater than in
      survivors (0.46 +/- 0.027 versus 0.22 +/- 0.017; p<0.01) over the first 5 days of
      intensive care. The mortality rate is 5% when ICC is less than 0, and 43% when
      above 0.7. ICC above 0.7 was associated with terminally elevated ICP (chi-square
      p=0.026). We propose that the Monro-Kellie doctrine can be monitored in real time
      to illustrate the state of intracranial volume regulation.

PMID- 21895520
TI  - Identification of plasma biomarkers of TBI outcome using proteomic approaches in
      an APOE mouse model.
AB  - The current lack of diagnostic and prognostic biomarkers for traumatic brain
      injury (TBI) confounds treatment and management of patients and is of increasing
      concern as the TBI population grows. We have generated plasma proteomic profiles
      from mice receiving TBI by controlled cortical impact at either 1.3 mm or 1.8 mm
      depth, comparing these against those of sham injured-animals to identify plasma
      biomarkers specific to mild or severe TBI at 24 hours, 1 month, or 3 months post
      injury. To identify possible prognostic biomarkers, we used apolipoprotein E
      (APOE)3 and APOE4 transgenic mice, which demonstrate relatively favorable and
      unfavorable outcomes respectively, following TBI. Using a quantitative proteomics
      approach (isobaric tagging for relative and absolute quantitation--iTRAQ) we have
      identified proteins that are significantly modulated as a function of TBI and
      also in response to the TBI*APOE genotype interaction, the latter representing
      potential prognostic biomarkers. These preliminary data clearly demonstrate
      plasma protein changes that are not only injury dependent but also interaction
      dependent. Importantly, these results demonstrate the presence of TBI-dependent
      and interaction-dependent plasma proteins at a 3-month time point, which is a
      considerable time post-injury in the mouse model, and will potentially be of
      significance for combat veterans receiving assessment at extended periods post
      injury. Furthermore, our identification of clusters of functionally related
      proteins indicates disturbance of particular biological modules, which
      potentially increases their value beyond that of solitary biomarkers.

PMID- 21895519
TI  - Mitochondrial injury after mechanical stretch of cortical neurons in vitro:
      biomarkers of apoptosis and selective peroxidation of anionic phospholipids.
AB  - Mechanical injury of neurites accompanied by rupture of mitochondrial membranes
      may lead to immediate nonspecific release and spreading of pro-apoptotic factors
      and activation of proteases, that is, execution of apoptotic program. In the
      current work, we studied the time course of the major biomarkers of apoptosis as
      they are induced by exposure of rat cortical neurons to mechanical stretch. By
      using transmission electron microscopy, we found that mitochondria in the
      neurites were damaged early (1 h) after mechanical stretch injury whereas somal
      mitochondria were significantly more resistant and demonstrated structural damage
      and degenerative mitochondrial changes at a later time point after stretch (12
      h). We also report that the stretch injury caused immediate activation of
      reactive oxygen species production followed by selective oxidation of a
      mitochondria-specific phospholipid, cardiolipin, whose individual peroxidized
      molecular species have been identified and quantified by electrospray ionization
      mass spectrometry analysis. Most abundant neuronal phospholipids -
      phosphatidylcholine, phophatidylethanolamine - did not undergo oxidative
      modification. Simultaneously, a small-scale release of cytochrome c was observed.
      Notably, caspase activation and phosphatidylserine externalization - two
      irreversible apoptotic events designating a point of no return - are
      substantially delayed and do not occur until 6-12 h after the initial impact. The
      early onset of reactive oxygen species production and cytochrome c release may be
      relevant to direct stretch-induced damage to mitochondria. The delayed emergence
      of apoptotic neuronal death after the immediate mechanical damage to mitochondria
      suggests a possible window of opportunity for targeted therapies.

PMID- 21895521
TI  - Limb/pelvis-hypoplasia/aplasia syndrome--further delineation of phenotype.
AB  - We report a case of Al-Awadi/Raas-Rothschild syndrome, an autosomal recessive
      disorder manifesting at an early gestation as hydrops as a result of congenital
      high airway obstruction.

PMID- 21895522
TI  - Alterations of A-type potassium channels in hippocampal neurons after traumatic
      brain injury.
AB  - Traumatic brain injury (TBI) is associated with cognitive deficits, memory
      impairment, and epilepsy. Previous studies have reported neuronal loss and
      neuronal hyperexcitability in the post-traumatic hippocampus. A-type K+ currents
      (I(A)) play a critical role in modulating the intrinsic membrane excitability of
      hippocampal neurons. The disruption of I(A) is reportedly linked to hippocampal
      dysfunction. The present study investigates the changes of I(A) in the
      hippocampus after TBI. TBI in rats was induced by controlled cortical impact. The
      impact induced a reproducible lesion in the cortex and an obvious neuronal death
      in the ipsilateral hippocampus CA3 region. At one week after TBI,
      immunohistochemical staining and Western blotting showed that the expression of
      I(A) channel subunit Kv4.2 was markedly decreased in the ipsilateral hippocampus,
      but remained unchanged in the contralateral hippocampus. Meanwhile,
      electrophysiological recording showed that I(A) currents in ipsilateral CA1
      pyramidal neurons were significantly reduced, which was associated with an
      increased neuronal excitability. Furthermore, there was an increased sensitivity
      to bicuculline-induced seizures in TBI rats. At 8 weeks after TBI,
      immunohistochemical staining and electrophysiological recording indicated that
      I(A) returned to control levels. These findings suggest that TBI causes a
      transient downregulation of I(A) in hippocampal CA1 neurons, which might be
      associated with the hyperexcitability in the post-traumatic hippocampus, and in
      turn leads to seizures and epilepsy.

PMID- 21895523
TI  - Lithium ameliorates neurodegeneration, suppresses neuroinflammation, and improves
      behavioral performance in a mouse model of traumatic brain injury.
AB  - Although traumatic brain injury (TBI) is recognized as one of the leading causes
      of death from trauma to the central nervous system (CNS), no known treatment
      effectively mitigates its effects. Lithium, a primary drug for the treatment of
      bipolar disorder, has been known to have neuroprotective effects in various
      neurodegenerative conditions such as stroke. Until this study, however, it has
      not been investigated as a post-insult treatment for TBI. To evaluate whether
      lithium could have beneficial effects following TBI, lithium at a dose of 1.5
      mEq/kg was administered after injury. Assessed at 3 days and 3 weeks post-injury
      using hematoxylin and eosin staining, lithium treatment was found to reduce
      lesion volume. Lithium at doses of 2.0 and 3.0 mEq/kg also significantly reduced
      lesion volume at 3 days after injury, and the therapeutic window was at least 3 h
      post-injury. TBI-induced neuronal death, microglial activation, and
      cyclooxygenase-2 induction were all attenuated by lithium at 3 days after injury.
      In addition, lithium treatment reduced TBI-induced matrix metalloproteinase-9
      expression and preserved the integrity of the blood-brain barrier. As for
      behavioral outcomes, lithium treatment reduced anxiety-like behavior in an open
      field test, and improved short- and long-term motor coordination in rotarod and
      beam-walk tests. Lithium robustly increased serine phosphorylation of glycogen
      synthase kinase-3beta (GSK-3beta), suggesting that the underlying mechanisms
      responsible for lithium's protective effects are triggered by increasing
      phosphorylation of this kinase and thereby inhibiting its activity. Our results
      support the notion that lithium has heretofore unrecognized capacity to mitigate
      the neurodegenerative effects and improve functional outcomes in TBI.

PMID- 21895524
TI  - Chronic exercise preserves renal structure and hemodynamics in spontaneously
      hypertensive rats.
AB  - AIMS: Exercise training (ExT) is a recommended adjunct to many pharmaceutical
      antihypertensive therapies. The effects of chronic ExT on the development of
      hypertension-induced renal injury remain unknown. We examined whether ExT would
      preserve renal hemodynamics and structure in the spontaneously hypertensive rat
      (SHR), and whether these effects were mediated by improved redox status and
      decreased inflammation. Normotensive WKY rats and SHR underwent moderate
      intensity ExT for 16 weeks. One group of SHR animals was treated with hydralazine
      to investigate the pressure-dependent/independent effects of ExT. Acute renal
      clearance experiments were performed prior to sacrifice. Tissue free radical
      production rates were measured by electron paramagnetic resonance; gene and
      protein expression were measured by real time RT-PCR and Western blot or
      immunofluorescence, respectively. Plasma angiotensin II levels and kidney
      antioxidants were assessed. Training efficacy was assessed by citrate synthase
      activity assay in hind-limb muscle. RESULTS: ExT delayed hypertension, prevented
      oxidative stress and inflammation, preserved antioxidant status, prevented an
      increase in circulating AngII levels, and preserved renal hemodynamics and
      structure in SHR. In addition, exercise-induced effects, at least, in part, were
      found to be pressure-independent. INNOVATION: This study is the first to provide
      mechanistic evidence for the renoprotective benefits of ExT in a model of
      hypertension. Our results demonstrate that initiation of ExT in susceptible
      patients can delay the development of hypertension and provide renoprotection at
      the functional and ultrastructural level. CONCLUSION: Chronic ExT preserves renal
      hemodynamics and structure in SHR; these effects are partially mediated by
      improved redox status and decreased inflammation.

PMID- 21895526
TI  - Specific loss of toll-like receptor 2 on bone marrow derived cells decreases
      atherosclerosis in LDL receptor null mice.
AB  - Innate immunity and, notably, Toll-like receptors (TLR), have an important role
      in atherogenesis. We have tested the hypothesis that the selective loss of TLR-2
      by cells of bone marrow (BM) origin will protect low-density receptor-deficient
      (Ldlr (-/-)) mice from both early- and late-stage atherosclerosis. BM cells from
      Tlr2(+/+) and Tlr2(-/-) littermates were used to reconstitute lethally irradiated
      Ldlr(-/-) mice. Following a recovery period, mice were placed either on a diet
      containing 21% saturated fat - 0.15% cholesterol for 8 weeks to study early-stage
      atherosclerosis, or on a diet richer in cholesterol (1.5%) for 16 weeks to study
      late-stage atherosclerosis. Donor cell Tlr2 genotype did not alter serum
      cholesterol levels or lipoprotein profiles in recipient animals. After 8 weeks on
      the 0.15% cholesterol diet, deficiency of TLR-2 expression on cells of BM origin
      reduced atherosclerosis in the aortic root and the aortic arch in both genders of
      mice. In contrast, the BM recipients who received the 1.5% cholesterol diet for
      16 weeks showed much larger lesions in the aortic root, and TLR-2 deficiency in
      BM cells failed to provide protection. Thus, TLR-2 expression in BM-derived cells
      contributes primarily to early stage atherosclerosis.

PMID- 21895527
TI  - The rise and fall of an epizootic of the diphyllobothriidean cestode
      Schistocephalus pungitii infecting the ninespine stickleback.
AB  - Epizootics of diphyllobothriidean cestodes appear to be simple, but deceptive
      similarity conceals the myriad ways in which these events are shaped by complex
      abiotic and biotic interactions. In Dog Bone Lake, Alaska, an epizootic of
      Schistocephalus pungitii infecting the ninespine stickleback (Pungitius
      pungitius) was short-lived. Its duration, with a peak that lasted only 1 yr, was
      shorter than for previously documented epizootics in Schistocephalus solidus .
      The ability of the ninespine stickleback to sustain infections, which appears to
      be related to species-specific characteristics of the host, may have played an
      important role in shaping the epizootic. Moreover, the epizootic of S. pungitii
      was not coincident with those observed for S. solidus in earlier studies within
      this region, supporting the hypothesis that processes involved in epizootics
      largely reflect local (lake-level) influences on population dynamics of the
      parasite. The outbreak occurred at a time when the host population was not
      relatively dense, which is inconsistent with epidemiological theory and may be a
      consequence of the parasite's indirect life cycle. The variability of the
      unregulated and unstable epizootic events of diphyllobothriidean cestodes
      presents a challenge to understand the ecological and evolutionary factors
      influencing the prevalence of infections in host populations.

PMID- 21895528
TI  - Phototherapy and the peripheral nervous system.

PMID- 21895525
TI  - Multiple arrhythmic syndromes in a newborn, owing to a novel mutation in SCN5A.
AB  - BACKGROUND: Mutations in the SCN5A gene have been linked to Brugada syndrome
      (BrS), conduction disease, Long QT syndrome (LQT3), atrial fibrillation (AF), and
      to pre- and neonatal ventricular arrhythmias. OBJECTIVE: The objective of this
      study is to characterize a novel mutation in Na(v)1.5 found in a newborn with
      fetal chaotic atrial tachycardia, post-partum intraventricular conduction delay,
      and QT interval prolongation. METHODS: Genomic DNA was isolated and all exons and
      intron borders of 15 ion-channel genes were sequenced, revealing a novel missense
      mutation (Q270K) in SCN5A. Na(v)1.5 wild type (WT) and Q270K were expressed in
      CHO-K1 with and without the Na(v)beta1 subunit. Results. Patch-clamp analysis
      showed ~40% reduction in peak sodium channel current (I(Na)) density for Q270K
      compared with WT. Fast and slow decay of I(Na) were significantly slower in
      Q270K. Steady-state activation and inactivation of Q270K channels were shifted to
      positive potentials, and window current was increased. The tetrodotoxin-sensitive
      late I(Na) was increased almost 3-fold compared with WT channels. Ranolazine
      reduced late I(Na) in WT and Q270K channels, while exerting minimal effects on
      peak I(Na). CONCLUSION: The Q270K mutation in SCN5A reduces peak I(Na) while
      augmenting late I(Na), and may thus underlie the development of atrial
      tachycardia, intraventricular conduction delay, and QT interval prolongation in
      an infant.

PMID- 21895530
TI  - Photomedicine and LLLT Literature Watch.

PMID- 21895531
TI  - Spinal cord injuries sustained in road crashes are not on the decrease in france:
      a study based on epidemiological trends.
AB  - Traumatic spinal cord injuries (SCI) are rare but extremely costly. In order to
      improve the modelling of inclusion criteria for studies of SCI it is necessary to
      determine what epidemiological trends affect SCI. Using the Rhone Registry, which
      contains all the casualties resulting from road crashes in the Rhone departement
      of France and codes their injuries using the Abbreviated Injury Scale (AIS), we
      describe the epidemiological trends that affect spinal cord injury (SCI), major
      spinal trauma (MST) and severe injuries (AIS4+) to other body regions between two
      periods 1996-2001 and 2003-2008. Although there has been a marked decrease (35%)
      in the incidence of casualties after a road traffic crash, and reductions of 22%
      in the incidence of MST and 33% in that of severe injuries (AIS4+) (p<0.001), for
      SCI the incidence rate and number of casualties have remained surprisingly
      stable. In the second period, there was no change in the incidence of SCI
      resulting from road traffic crashes, nor in the associated fatality, mortality
      and survival rates. The incidence for car users was significantly lower in the
      second period. This contrasts with the incidences for motorcyclists and for the
      group including pedestrians and cyclists which were respectively 47% and 77%
      higher in the second period. The median age of the casualties, the age-adjusted
      incidence of SCI and the number of associated injuries were also higher in the
      second period. We have observed a marked reduction in the incidence of road
      trauma including the most severe injuries, but not SCI. The higher proportion of
      motorcyclists, the increase in the age of casualties and the greater presence of
      multiple injuries are new factors in the epidemiology of SCI after a road crash.

PMID- 21895532
TI  - Endogenous GFAP-positive neural stem/progenitor cells in the postnatal mouse
      cortex are activated following traumatic brain injury.
AB  - Interest in promoting regeneration of the injured nervous system has recently
      turned toward the use of endogenous stem cells. Elucidating cues involved in
      driving these precursor cells out of quiescence following injury, and the signals
      that drive them toward neuronal and glial lineages, will help to harness these
      cells for repair. Using a biomechanically validated in vitro organotypic stretch
      injury model, cortico-hippocampal slices from postnatal mice were cultured and a
      stretch injury equivalent to a severe traumatic brain injury (TBI) applied. In
      uninjured cortex, proliferative potential under in vitro conditions is virtually
      absent in older slices (equivalent postnatal day 15 compared to 8). However,
      following a severe stretch injury, this potential is restored in injured outer
      cortex. Using slices from mice expressing a fluorescent reporter on the human
      glial fibrillary acidic protein (GFAP) promoter, we show that GFAP+ cells account
      for the majority of proliferating neurospheres formed, and that these cells are
      likely to arise from the cortical parenchyma and not from the subventricular
      zone. Moreover, we provide evidence for a correlation between upregulation of
      sonic hedgehog signaling, a pathway known to regulate stem cell proliferation,
      and this restoration of regenerative potential following TBI. Our results
      indicate that a source of quiescent endogenous stem cells residing in the cortex
      and subcortical tissue proliferate in vitro following TBI. Moreover, these
      proliferating cells are multipotent and are derived mostly from GFAP-expressing
      cells. This raises the possibility of using this endogenous source of stem cells
      for repair following TBI.

PMID- 21895534
TI  - Insulin-regulated aminopeptidase deficiency provides protection against ischemic
      stroke in mice.
AB  - Recent studies have demonstrated that angiotensin IV (Ang IV) provides protection
      against brain injury caused by cerebral ischemia. Ang IV is a potent inhibitor of
      insulin-regulated aminopeptidase (IRAP). Therefore, we examined the effect of
      IRAP gene inactivation on neuroprotection following transient middle cerebral
      artery occlusion (MCAo) in mice. IRAP knockout mice and wild-type controls were
      subjected to 2 h of transient MCAo using the intraluminal filament technique.
      Twenty-four hours after reperfusion, neurological deficits of the stroke-induced
      mice were assessed and infarct volumes were measured by TTC staining. The
      cerebral infarct volume was significantly reduced in the IRAP knockout mice
      compared to wild-type littermates with corresponding improvement in neurological
      performance at 24 h post-ischemia. An increase in compensatory cerebral blood
      flow during MCAo was observed in the IRAP knockout animals with no differences in
      cerebral vascular anatomy detected. The current study demonstrates that deletion
      of the IRAP gene protects the brain from ischemic damage analogous to the effect
      of the IRAP inhibitor, Ang IV. This study indicates that IRAP is potentially a
      new therapeutic target for the development of treatment for ischemic stroke.

PMID- 21895533
TI  - Cyclin D1 gene ablation confers neuroprotection in traumatic brain injury.
AB  - Cell cycle activation (CCA) is one of the principal secondary injury mechanisms
      following brain trauma, and it leads to neuronal cell death, microglial
      activation, and neurological dysfunction. Cyclin D1 (CD1) is a key modulator of
      CCA and is upregulated in neurons and microglia following traumatic brain injury
      (TBI). In this study we subjected CD1-wild-type (CD1(+/+)) and knockout (CD1(-/
      )) mice to controlled cortical impact (CCI) injury to evaluate the role of CD1 in
      post-traumatic neurodegeneration and neuroinflammation. As early as 24 h post
      injury, CD1(+/+) mice showed markers of CCA in the injured hemisphere, including
      increased CD1, E2F1, and proliferating cell nuclear antigen (PCNA), as well as
      increased Fluoro-Jade B staining, indicating neuronal degeneration. Progressive
      neuronal loss in the hippocampus was observed through 21 days post-injury in
      these mice, which correlated with a decline in cognitive function. Microglial
      activation in the injured hemisphere peaked at 7 days post-injury, with sustained
      increases at 21 days. In contrast, CD1(-/-) mice showed reduced CCA and
      neurodegeneration at 24 h, as well as improved cognitive function, attenuated
      hippocampal neuronal cell loss, decreased lesion volume, and cortical microglial
      activation at 21 days post-injury. These findings indicate that CD1-dependent CCA
      plays a significant role in the neuroinflammation, progressive neurodegeneration,
      and related neurological dysfunction resulting from TBI. Our results further
      substantiate the proposed role of CCA in post-traumatic secondary injury, and
      suggest that inhibition of CD1 may be a key therapeutic target for TBI.

PMID- 21895535
TI  - Human involucrin promoter mediates repression-resistant and compartment-specific
      LEKTI expression.
AB  - Gene-modified skin grafts, produced through gene transfer to human keratinocyte
      stem cells, offer the possibility of therapeutic benefit for inherited skin
      diseases. We have previously described efficient lentiviral vector-mediated gene
      transfer to keratinocyte stem cells and the generation of human skin grafts for
      the inherited skin disease, Netherton syndrome, which arises due to mutations in
      serine protease inhibitor Kazal-type 5 (SPINK5). Vectors incorporating an
      internal murine retroviral-derived promoter [spleen focus-forming virus (SFFV)]
      in combination with a codon-optimized SPINK5 transgene supported high levels of
      reconstitution and robust correction of skin architecture. Subsequent longer-term
      experiments have uncovered unanticipated silencing phenomena, with loss of SPINK5
      gene expression over time. The inadvertent introduction of CpG sites during codon
      optimization appears to have rendered vectors susceptible to silencing due to
      methylation across the promoter-transgene boundary. Substitution of the
      methylation-susceptible SFFV promoter with a 572-bp minimal human involucrin
      promoter (INVOp), which encodes very few CpG sites, prevented repression of the
      SPINK5 transgene and resulted in durable and highly compartment-specific
      reconstitution of lympho-epithelial Kazal-type-related inhibitor (LEKTI) in human
      skin grafted onto immunodeficient mice. We conclude that skin grafts modified
      with lentiviral vectors encoding INVOp offer a suitable platform for therapeutic
      gene therapy in Netherton syndrome, and our experience highlights unanticipated
      effects of transgene codon optimization.

PMID- 21895536
TI  - Response to intra-arterial oncolytic virotherapy with the herpes virus NV1020
      evaluated by [18F]fluorodeoxyglucose positron emission tomography and computed
      tomography.
AB  - Oncolytic virotherapy poses unique challenges to the evaluation of tumor
      response. We hypothesized that the addition of [(18)F]fluorodeoxyglucose (FDG)
      positron emission tomography (PET) to standard computed tomography (CT)
      evaluation would improve diagnostic and prognostic power of the measurement of
      tumor response to oncolytic virotherapy. A phase I/II trial was conducted to
      investigate treatment of hepatic metastases from colorectal carcinoma using intra
      arterial administration of the oncolytic herpes virus NV1020. Both contrast
      enhanced CT and FDG PET were obtained on each patient at each time point.
      Quantitative FDG PET and CT responses were correlated with each other and with
      clinical outcome metrics. A majority of patients showed initial post-viral
      infusion increases in tumor size (69%) or in standardized uptake value (SUV)
      (80%) large enough to qualify as progressive disease. Most showed subsequent
      decreases in tumor size (64%) or SUV (83%) enough to be reclassified as partial
      response or stable disease. Late PET and CT imaging results correlated well with
      each other and with clinical outcomes, but results from early in the treatment
      scheme did not correlate with each other, with later results, or with clinical
      outcomes. The addition of FDG PET to the evaluation of tumor response to the
      oncolytic virus NV1020 did not provide useful diagnostic or prognostic data. More
      sophisticated molecular imaging will need to be developed to monitor the effects
      of this novel class of antineoplastic agents.

PMID- 21895537
TI  - Splitting of the umbilical cord in a 13-week-old fetus.
AB  - There is an increasing interest in the physiology and pathology of the umbilical
      cord because it is recognized as an important source of placental and,
      consequently, fetal problems. During the postmortem examination of a severely
      macerated 13-week-old fetus, a split umbilical cord was noted. This rare finding
      was seen in the middle segment of the cord, the fetal and placental ends both
      being normal. The pathogenesis of this lesion is not fully understood, and it is
      possible that it results through focal degeneration of previously formed
      Wharton's jelly or secondary loss of Wharton's jelly due to incomplete fusion or
      hypoplasia of the amniotic covering. Whatever the pathogenesis, it is assumed
      that an umbilical vessel devoid of its protective Wharton's jelly is more prone
      to compression and thrombosis with all its deleterious effects. Death in this
      case was probably associated with the congenital heart defect also presented by
      the fetus. The rarity of this lesion is probably explained by the fact that it
      represents the end of the spectrum of longitudinal deficiency of Wharton's jelly,
      a relatively common finding.

PMID- 21895538
TI  - The clinical development of FLT3 inhibitors in acute myeloid leukemia.
AB  - INTRODUCTION: Activating mutations of the FMS-like tyrosine kinase 3 (FLT3) gene
      occur at high frequency in acute myeloid leukemia (AML), being detected in > 30%
      of patients at diagnosis and carrying a profound negative prognostic impact. The
      development of effective small molecule inhibitors of FLT3 has been the focus of
      an intensive international research effort in recent years. AREAS COVERED: The
      published results of the first decade of clinical trials of FLT3-targeted
      tyrosine kinase inhibitors are critically reviewed. Over this period, a first
      generation of compounds has followed an orderly progression from monotherapy
      studies through combination with chemotherapy and into advanced stage
      international trials in both relapsed and newly-diagnosed AML. Correlative
      laboratory studies performed alongside several of these studies have been highly
      illuminating, demonstrating close correlations between clinical activity and
      effective inhibition of FLT3, and highlighting potential drug resistance
      mechanisms. EXPERT OPINION: Clinical responses to several of the early multi
      targeted agents were hindered by unfavorable pharmacokinetics and lack of
      potency. Newer, more potent FLT3 inhibitors such as sorafenib and AC220 possess
      the ability to achieve more sustained in vivo inhibition of FLT3 and have shown
      highly promising activity in early clinical studies. As these agents enter
      advanced stage trials, they carry the potential to make a major clinical impact
      in this disease. In future, FLT3 inhibitors may be effectively used in
      combination with other molecularly targeted agents.

PMID- 21895539
TI  - AE37: a novel T-cell-eliciting vaccine for breast cancer.
AB  - INTRODUCTION: Immunotherapy, including vaccines targeting the human EGFR2 (HER
      2/neu) protein, is an active area of investigation in combatting breast cancer.
      Several vaccines are currently undergoing clinical trials, most of which are
      CD8(+) T-cell-eliciting vaccines. AE37 is a promising primarily CD4(+) T-cell
      eliciting HER-2/neu breast cancer vaccine currently in clinical trials. AREAS
      COVERED: This article reviews preclinical investigations as well as findings from
      completed and ongoing Phase I and Phase II clinical trials of the AE37 vaccine.
      EXPERT OPINION: Clinical trials have shown the AE37 vaccine to be safe and
      capable of generating peptide-specific, durable immune responses. This has been
      shown in patients with any level of HER-2/neu expression. Early clinical findings
      suggest there may be benefit to AE37 vaccination in preventing breast cancer
      recurrence.

PMID- 21895540
TI  - Drug delivery strategies for poorly water-soluble drugs: the industrial
      perspective.
AB  - INTRODUCTION: For poorly soluble compounds, a good bioavailability is typically
      needed to assess the therapeutic index and the suitability of the compound for
      technical development. In industry, the selection of the delivery technology is
      not only driven by technical targets, but also by constraints, such as production
      costs, time required for development and the intellectual property situation.
      AREAS COVERED: This review covers current developments in parenteral and oral
      delivery technologies and products for poorly water-soluble compounds, such as
      nano-suspensions, solid dispersions and liposomes. In addition, the use of
      biorelevant dissolution media to assess dissolution and solubility properties is
      described. Suggestions are also included to systematically address development
      hurdles typical of poorly water-soluble compounds intended for parenteral or oral
      administration. EXPERT OPINION: A holistic assessment is recommended to select
      the appropriate delivery technology by taking into account technical as well as
      intellectual property considerations. Therefore, first and foremost, a
      comprehensive physico-chemical characterization of poorly water-soluble compounds
      can provide the key for a successful selection and development outcome. In this
      context, the identified physical form of the compound in the formulation is used
      as a guide for a risk-benefit assessment of the selected oral delivery
      technology. The potential of nano-suspensions for intravenous administration is
      unclear. In the case of oral administration, nano-suspensions are mainly used to
      improve the oral absorption characteristics of micronized formulations. The
      development of an in situ instantaneous solubilization method, based on stable,
      standardized liposomes with low toxicity, opens new avenues to solubilize poorly
      water-soluble compounds.

PMID- 21895541
TI  - Lactoferrin delivery systems: approaches for its more effective use.
AB  - INTRODUCTION: Recently, pharmacotherapy has advanced extensively, but there are
      still many refractory diseases which cannot be solved fully by existing
      therapeutic agents. Therefore, alternative medicine and health foods are now
      attracting much attention, for example, lactoferrin (LF): a multifunctional
      glycoprotein. As LF is non-toxic and low-cost, its application in healthcare and
      therapeutics is expected to be widespread. AREAS COVERED: In this review, LF's
      general basic features are described. The interaction of LF with its receptors
      activates the immune system, including cytokine production and balance. In
      particular, the immune activation of orally administered LF is considered as a
      new strategy for the treatment of refractory diseases, such as inflammatory bowel
      disease, virus infection and tumor metastasis. Also mentioned are the problems
      associated with the use of LF. As LF is degraded rapidly in the body due to
      enzymatic hydrolysis, high amounts or frequent dosing is required; an appropriate
      delivery system may improve these problems and increase its efficiency. EXPERT
      OPINION: Chemical modifications, such as PEGylation, can enhance the stability of
      LF in the body, resulting in increased efficacy. Also, liposomes and enteric or
      microparticulate formulations can promote the function of LF in oral
      administration due to target site delivery and protection of LF from enzymatic
      hydrolysis. These delivery systems are expected to improve the utility of LF.

PMID- 21895542
TI  - Challenges to antiretroviral therapy: can one sentence in medication labelling
      reduce adherence?

PMID- 21895543
TI  - Cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab versus
      epirubicin, cyclophosphamide, vinblastine, prednisone and rituximab for the
      initial treatment of elderly "fit" patients with diffuse large B-cell lymphoma:
      results from the ANZINTER3 trial of the Intergruppo Italiano Linfomi.
AB  - We conducted a prospective study to compare epirubicin, cyclophosphamide,
      vinblastine, prednisone and rituximab (R-miniCEOP) with cyclophosphamide,
      doxorubicin, vincristine, prednisone and rituximab (R-CHOP) for the treatment of
      "fit" elderly patients with diffuse large B-cell lymphoma (DLBCL). Patients over
      the age of 65 with stage II-IV DLBCL were screened with a comprehensive geriatric
      assessment. Patients were randomized to receive six courses of R-miniCEOP (n =
      114) or R-CHOP (n = 110). Overall, the rate of complete remission was 70% (p =
      0.466). After a median follow-up of 42 months, 5-year event-free survival (EFS)
      rates were 46% and 48% for R-miniCEOP and R-CHOP, respectively (p = 0.538).
      Patients older than 72 years and with low-risk disease had a better outcome when
      treated with R-miniCEOP (p = 0.011). Overall R-CHOP and R-miniCEOP are similarly
      effective for elderly "fit" patients with DLBCL. The less intense R-miniCEOP may
      be an acceptable option for the treatment of relatively older patients with low
      risk disease.

PMID- 21895544
TI  - Epiphora as the presenting sign in unsuspected B cell lymphoma.

PMID- 21895545
TI  - Prognostic value of serum CD44, intercellular adhesion molecule-1 and vascular
      cell adhesion molecule-1 levels in patients with indolent non-Hodgkin lymphomas.
AB  - Elevated serum CD44, intercellular adhesion molecule-1 (ICAM-1) and vascular cell
      adhesion molecule-1 (VCAM-1) have been linked to poor prognosis in aggressive
      lymphomas, but their utility in low grade lymphomas remains undefined. We
      evaluated serum CD44, VCAM-1 and ICAM-1 levels in 100 patients with newly
      diagnosed indolent NHL. The median pre-treatment values of the markers were as
      follows: CD44 540 ng/mL (range 156-1201), ICAM-1 311 ng/mL (range 102-1222) and
      VCAM-1 1165 ng/mL (range 248-4779). On univariate analysis, elevated sCD44, sICAM
      1 and sVCAM-1 were significantly associated with worse overall (OS) and
      progression-free survival (PFS). In a subset analysis of patients with stage IV
      disease, the effects of sCD44 and sICAM-1 on OS persisted (p<0.05), as did the
      effect of sCD44 on PFS (p<0.01). In a multivariate analysis that included
      conventional prognostic factors and the Follicular Lymphoma International
      Prognostic Index (FLIPI) model, sICAM-1 demonstrated prognostic value for OS and
      PFS. We conclude that serum CD44, ICAM-1 and VCAM-1 can potentially be prognostic
      in patients with indolent NHL. Though the FLIPI model remains the gold standard
      for prognosis, these quantitative serologic markers may be useful as adjunct
      tools in assessing disease risk.

PMID- 21895546
TI  - A rapid and simple assay for human blood malignancy engraftment, homing and
      chemotherapy treatment using fluorescent imaging of avian embryos.
AB  - Detection of grafted human cells in mice using fluorescence is a rapid and simple
      technique whose use is continually expanding. Robust engraftment of human
      hematological malignancy (HHM) lines and patient cells into the naturally
      immunodeficient turkey embryo has recently been demonstrated by polymerase chain
      reaction (PCR), fluorescence activated cell sorting (FACS) and histology. We
      demonstrate here that fluorescence imaging is a rapid and simple technique for
      detecting engraftment and homing of cells derived from HHM in turkey embryos.
      Raji lymphoma cells expressing a far-red fluorescent protein were injected
      intravascularly into turkey embryos and fluorescence was detected 8 days later in
      their limbs and skulls. Much stronger signals were obtained after removal of the
      bones from the limbs. Unlabeled Raji cells did not give a fluorescent signal.
      Treatment with doxorubicin dramatically reduced the fluorescent signal.
      Intravenously injected HL-60 leukemia cells labeled with infrared-fluorescing dye
      were detected in the bone marrow after 16 h. Homing was active, although some non
      specific fluorescence was present. Use of fluorescence imaging of HHM in turkey
      embryos is therefore feasible and reduces the time, effort and expense for
      detecting engraftment. This technique has potential to become a high-throughput
      xenograft system for hematological chemotherapy development and testing, and for
      study of hematological cell homing.

PMID- 21895547
TI  - Modifying the immune system to treat chronic lymphocytic leukemia.

PMID- 21895548
TI  - What's new in the treatment of neonatal shock.
AB  - Shock is a clinical disorder that challenges caregivers in the neonatal intensive
      care unit. The predominant cause of shock in neonates is sepsis. This article
      provides an overview of the current treatment of septic shock with particular
      emphasis on newer vasoactive drugs (milrinone, levosimendan and vasopressin) to
      support cardiovascular dysfunction.

PMID- 21895549
TI  - Nitric oxide: orchestrator of endothelium-dependent responses.
AB  - The present review first summarizes the complex chain of events, in endothelial
      and vascular smooth muscle cells, that leads to endothelium-dependent relaxations
      (vasodilatations) due to the generation of nitric oxide (NO) by endothelial
      nitric oxide synthase (eNOS) and how therapeutic interventions may improve the
      bioavailability of NO and thus prevent/cure endothelial dysfunction. Then, the
      role of other endothelium-derived mediators (endothelium-derived hyperpolarizing
      (EDHF) and contracting (EDCF) factors, endothelin-1) and signals (myoendothelial
      coupling) is summarized also, with special emphasis on their interaction(s) with
      the NO pathway, which make the latter not only a major mediator but also a key
      regulator of endothelium-dependent responses.

PMID- 21895550
TI  - Synthesis and hemocompatibity evaluation of segmented polyurethane end-capped
      with both a fluorine tail and phosphatidylcholine polar headgroups.
AB  - To improve the hemocompatibility of polyurethanes, an amine monomer containing a
      long fluorine tail and phosphatidylcholine polar headgroups, 2-amino-3-oxo-3-(2
      (2,2,3,3,4,4,5,5,6,6,7,7,8,8,8-pentadecafluorooctan amido) ethyl amino) propyl
      phosphorylcholine (FASPC) was firstly synthesized and characterized. Then four
      kinds of fluorinated phosphatidylcholine end-capped polyurethanes with different
      chemical structures were prepared. The surface properties of these prepared
      polyurethanes were characterized using X-ray photoelectron spectroscopic analysis
      (XPS) and water contact angle measurements. The results indicated that the
      phosphatidylcholine (PC) polar headgroups along with the fluorine tail could be
      easily enriched on the top surfaces, and the PC groups could be highly oriented
      on the outmost surface when the polymer film was in contact with water for only
      30 s at room temperature. The evaluation of hemocompatibity was carried out via
      fibrinogen adsorption and platelet adhesion. Fibrinogen adsorption (37 degrees C
      for 90 min) decreased by 98% to 87% compared to that on ordinary polyurethane
      surfaces, and almost no platelet adhesion and activation was observed at 37
      degrees C for 2 h.

PMID- 21895551
TI  - Signalling pathways of insulin-like growth factors (IGFs) and IGF binding protein
      3.
AB  - Although the insulin-like growth factor (IGF) system is essential for normal
      growth and development, its dysregulation has been implicated in a range of
      pathological states. The peptide growth factors IGF-I and IGF-II exert their
      effects by binding to cell-surface heterotetrameric tyrosine kinase receptors and
      activating multiple intracellular signalling cascades, leading to changes in the
      expression of proteins essential for cell proliferation, survival and
      differentiation. The IGF system comprises multiple ligands, receptors and high
      affinity IGF binding proteins (IGFBPs), with added complexity arising from
      crosstalk between its receptors and other key growth-regulatory pathways such as
      those activated by steroid hormones, integrins and other receptor tyrosine
      kinases. The IGFBPs are also increasingly recognised for their intrinsic growth
      regulatory activity, and the ability of IGFBP-3 to modulate signalling pathways
      of nuclear hormone and growth factor receptors, as well as novel receptors, is
      believed to play a role both in normal physiology and in disease.

PMID- 21895552
TI  - Traffic death trends in children aged 0-14 years in Lithuania: patterns by age
      group.
AB  - The aim of the study was to analyse traffic-injury mortality trends in children
      aged 0-14 years in Lithuania between 1971 and 2005. The data was derived from
      Statistics Lithuania. Trends were estimated by the use of cubic regression. In
      addition, data from 'tail' years was compared, and the t-test was used. The
      significance level p <=0.05 was considered statistically significant. In the age
      groups 1-4 and 5-9 years, traffic injury mortality showed significantly
      decreasing trends, but in the age group 10-14 years, no significant tendencies
      have been observed. Traffic deaths as a proportion of injury deaths and as a
      proportion of all deaths have risen significantly in the age groups 1-4 and 10-14
      years. In children aged 5-9 years, for traffic deaths percentage of injury
      deaths, no significance change was observed, and significant decrease was shown
      for traffic deaths percentage of all deaths. The study showed that in road safety
      work, more attention should be given to young adolescents aged 10-14 years and to
      children aged 1-4 years. A public health approach, effective law enforcements and
      community involvement are recommended for road safety management.

PMID- 21895553
TI  - Current review of antimicrobial treatment of nosocomial pneumonia caused by
      multidrug-resistant pathogens.
AB  - Nosocomial pneumonia (including ventilator-associated pneumonia; VAP), a
      consistently difficult-to-treat entity, is frequently caused by multidrug
      resistant (MDR) or pandrug-resistant (PDR) bacteria. Given the high mortality
      rates caused by drug-resistant bacteria and the difficulty of developing new
      potent antibiotics to target the problematic pathogens, combination regimens are
      under ardent evaluation as new strategies to overcome increasing drug resistance.
      Adjustment of the administration method of certain beta-lactams (meropenem, or
      imipenem/cilastatin), or combination of tigecycline with some agents, may show
      promise with regard to successful management of MDR or PDR Acinetobacter
      baumannii pneumonia. Additionally, vancomycin plus rifampicin is an effective
      regimen against nosocomial pneumonia caused by methicillin-resistant
      Staphylococcus aureus (MRSA) responding poorly to vancomycin monotherapy. The
      clinical appropriateness of parenteral colistin against pneumonia caused by MDR
      A. baumannii has been established in a clinical trial. Facing the decline of
      clinical vancomycin efficacy after initial use, linezolid might be the drug of
      choice with regard to the treatment of MRSA-VAP. The role of tigecycline
      monotherapy for the management of nosocomial pneumonia caused by MRSA and
      extended-spectrum beta-lactamase-producing Enterobacteriaceae needs to be
      cautiously evaluated.

PMID- 21895554
TI  - Escitalopram for the treatment of major depressive disorder in youth.
AB  - INTRODUCTION: Major depressive disorder (MDD) is a serious public problem,
      affecting 4 - 6% of adolescents at any one time. Although adolescent MDD needs
      early and appropriate intervention, concerns regarding the risk of suicidality
      associated with antidepressant treatment and efficacy of pharmacotherapy have led
      to decreased use of antidepressants in children and adolescents. After the
      approval of fluoxetine in 2003, escitalopram received FDA approval in 2009 for
      the acute and maintenance treatment of MDD in adolescent patients. AREAS COVERED:
      The paper addressed the following questions: Is escitalopram effective for
      adolescent MDD? How large is the magnitude of effectiveness? Does escitalopram
      treatment have any benefit in adolescents compared with the risk of suicidal
      behavior and treatment-emergent adverse events? EXPERT OPINION: The efficacy of
      escitalopram in adolescent MDD was demonstrated in a double-blind, randomized,
      controlled trial and extrapolated from a similar citalopram trial. The optimal
      dose is 10 mg/day and the magnitude of the antidepressant effect is modest.
      Escitalopram treatment is generally well tolerated by adolescents, but treatment
      emergent agitation, suicidal behavior and manic symptoms should be closely
      monitored. Escitalopram can be used as one of the first-line treatment options
      for moderate to severe MDD in adolescents.

PMID- 21895555
TI  - Detection of activity limitations in older adults with MCI or Alzheimer's disease
      through evaluation of perceived difficulty in use of everyday technology: a
      replication study.
AB  - OBJECTIVES AND METHODS: Earlier research indicates that the ability to use
      everyday technology (ET) may be sensitive to subtle functional change. People
      with mild cognitive impairment (MCI) have been identified as significantly more
      disabled in ET use compared to controls, albeit less disabled than people with
      dementia. The aim of this study was to investigate the replicability of these
      findings using an improved version of the Everyday Technology Use Questionnaire
      (ETUQ) to compare perceptions of relevance and difficulty in ET use in
      participants with MCI or Alzheimer's disease (AD) and controls. Additional aims
      were to explore the validity of ETUQ, and the relationships between perceived
      difficulty in ET use and cognitive status, mood state, and involvement in
      everyday life activities. In total, 118 participants were included, 37 with AD,
      37 with MCI, and 44 controls. RESULTS: Analyses confirmed that the rating scale
      of the ETUQ functioned well. The three groups overlapped but differed
      significantly in their perceptions of ETs relevance (p < 0.05) as well as of
      difficulties in ET use (p < 0.001). Moderate correlations were also found between
      ETUQ measures and cognitive status, mood, and involvement in activities, the
      strongest being that between ETUQ measures and involvement in activities (r =
      0.563). CONCLUSION: Taken together, the findings underscore the plausibility of
      disability already in people with MCI, as the use of ET strongly correlates to
      involvement in activities. It is therefore important that professionals who meet
      older adults with cognitive impairment take this aspect of function into account
      in assessments and targeted interventions.

PMID- 21895556
TI  - Three-dimensional finite element analysis of the maxillary central incisor in two
      different situations of traumatic impact.
AB  - Dental trauma is one of the most common events in dental practice. However, few
      studies have investigated the biomechanical characteristics of these injuries.
      The objective of this study was to analyse the stress distribution in the
      dentoalveolar structures of a maxillary central incisor subjected to two
      situations of impact loading. The following loading forces were applied using a
      3D finite element model: a force of 2000 N acting at an angle of 90 degrees on
      the buccal surface of the crown and a vertical 2000 N force acting in the
      cleidocranial direction on the incisal surface of the tooth. Harmful stresses
      were observed in both situations, causing damage to both the tooth and adjacent
      tissue. However, the damage found in soft tissues such as periodontal ligament
      and dental pulp was negligible. In conclusion, injuries resulting from the
      traumatic situations were more damaging to the integrity of the tooth and its
      associated hard-tissue structures.

PMID- 21895558
TI  - The effect of noun animacy on the processing of unambiguous sentences: evidence
      from French relative clauses.
AB  - Two experiments, one using self-paced reading and one using eye tracking,
      investigated the influence of noun animacy on the processing of subject relative
      (SR) clauses, object relative (OR) clauses, and object relative clauses with
      stylistic inversion (OR-SI) in French. Each sentence type was presented in two
      versions: either with an animate relative clause (RC) subject and an inanimate
      object (AS/IO), or with an inanimate RC subject and an animate object (IS/AO).
      There was an interaction between the RC structure and noun animacy. The advantage
      of SR sentences over OR and OR-SI sentences disappeared in AS/IO sentences. The
      interaction between animacy and structure occurred in self-paced reading times
      and in total fixation times on the RCs, but not in first-pass reading times. The
      results are consistent with a late interaction between animacy and structural
      processing during parsing and provide data relevant to several models of parsing.

PMID- 21895559
TI  - Some effort for some: further evidence that scalar implicatures are effortful.
AB  - Under the assumption of the principle of cooperation (Grice, 1989), a statement
      such as "some eels are fish" is thought to be false since it contains less
      information than is considered sufficient. However, the statement is logically
      sound since the meaning of "some" is compatible with "all". Currently, the
      primary interpretation of such underinformative statements remains subject to
      debate. According to Levinson (2000), the pragmatic "some but not all"
      interpretation is the default interpretation, while others (e.g., Sperber &
      Wilson, 1995) argue that this pragmatic interpretation only comes to the fore
      when relevant within the context and is thus considered secondary to the logical
      "some and perhaps all" interpretation. In this study, three factors that may
      influence the answer pattern are studied: task load, working memory capacity, and
      repetition of the statements. In Experiment 1, we used a secondary task paradigm
      to manipulate the cognitive load under which a number of underinformative
      statements had to be judged. We observed that for participants with a rather
      limited working memory span it is harder to reach a pragmatic interpretation
      under cognitive load. In Experiment 2, we manipulated the repetition of the
      statements. We observed that with a higher number of filler statements,
      participants produced fewer consistent answer patterns. This study provides
      further evidence against the automaticity of the pragmatic interpretation: It
      shows that the pragmatic interpretation requires more cognitive effort than the
      logical interpretation and that increasing the number of filler statements
      inhibits the development of a response strategy.

PMID- 21895560
TI  - Influence of multiple-day temporal distribution of repetitions on memory: a
      comparison of uniform, expanding, and contracting schedules.
AB  - Very few studies have examined the influence of schedules of repetitions across
      multiple days (e.g., Tsai,  1927 ). Three temporal schedules of four
      presentations of pseudoword/word pairs over a 7-day learning period were
      compared: a uniform (presentations on Days 1, 3, 5, and 7), an expanding (1, 2,
      3, 7), and a contracting (1, 5, 6, 7) schedule. Schedule was a within-subjects
      variable. Experiment 1 was performed on the Internet and showed that cued recall
      on Day 9 led to higher scores for the stimuli of the expanding schedule.
      Experiment 2 was performed in the laboratory and showed that the expanding and
      the uniform schedules led to the highest scores on Day 9. A recognition task
      performed during the learning phase revealed that stimuli recognized at the time
      of their repetition were more likely to be retrieved later than the others. Our
      results are discussed within the framework of the study-phase retrieval and
      encoding variability theories.

PMID- 21895561
TI  - Sound symbolic naming of novel objects is a graded function.
AB  - Although linguistic traditions of the last century assumed that there is no link
      between sound and meaning (i.e., arbitrariness), recent research has established
      a nonarbitrary relation between sound and meaning (i.e., sound symbolism). For
      example, some sounds (e.g., /u/ as in took) suggest bigness whereas others (e.g.,
      /i/ as in tiny) suggest smallness. We tested whether sound symbolism only marks
      contrasts (e.g., small versus big things) or whether it marks object properties
      in a graded manner (e.g., small, medium, and large things). In two experiments,
      participants viewed novel objects (i.e., greebles) of varying size and chose the
      most appropriate name for each object from a list of visually or auditorily
      presented nonwords that varied incrementally in the number of "large" and "small"
      phonemes. For instance, "wodolo" contains all large-sounding phonemes, whereas
      "kitete" contains all small-sounding phonemes. Participants' choices revealed a
      graded relationship between sound and size: The size of the object linearly
      predicted the number of large-sounding phonemes in its preferred name. That is,
      small, medium, and large objects elicited names with increasing numbers of large
      sounding phonemes. The results are discussed in relation to cross-modal
      processing, gesture, and vocal pitch.

PMID- 21895562
TI  - Recognition of own- and other-race faces in autism spectrum disorders.
AB  - Empirical data regarding the extent of face recognition abnormalities in autism
      spectrum disorder (ASD) is inconsistent. Here, 27 ASD and 47 typically developing
      (TD) children completed an immediate two-alternative forced-choice identity
      matching task. We contrasted recognition of own- and other-race faces, and,
      counter to prediction, we found a typical advantage for recognizing own- over
      other-race faces in both the ASD and TD groups. In addition, ASD and TD groups
      responded similarly to stimulus manipulations (use of identical or different
      photographs for identity matching and cropping stimuli to remove hair
      information). However, age-standardized scores varied widely within the ASD
      sample, and a subgroup of ASD participants with impaired face recognition did not
      exhibit a significant own-race recognition advantage. An explanation regarding
      early experience with faces is considered, and implications for research of
      individual variation within ASD are discussed.

PMID- 21895563
TI  - Layer-by-layer tissue microfabrication supports cell proliferation in vitro and
      in vivo.
AB  - Layer-by-layer biofabrication represents a novel strategy to create three
      dimensional living structures with a controlled internal architecture, using cell
      micromanipulation technologies. Laser assisted bioprinting (LAB) is an effective
      printing method for patterning cells, biomolecules, and biomaterials in two
      dimensions. "Biopapers," made of thin polymer scaffolds, may be appropriate to
      achieve three-dimensional constructs and to reinforce mechanical properties of
      printed materials. The aim of this work was to evaluate the effect of the
      tridimensional organization of cells and biomaterials on cell proliferation in
      vitro and in vivo. The experimental LAB setup was comprised of an infrared laser,
      focused onto a glass ribbon coated with an absorbing layer of gold. The cell
      bioink was made of MG63 cells (50 millions cells/mL in culture medium and 1%
      alginate), transduced with Luciferase gene for tracking and quantification. The
      printing substrate was a 100-MUm-thick polycaprolacton (PCL) electrospun
      scaffold. The building sequence comprised sequential layers of cells and PCL
      scaffolds stacked using two different tridimensional arrangements, which were
      compared in this study (layer-by-layer vs. seeding on a single locus of the
      scaffolds). Then the cell-seeded materials were cultured in vitro or implanted in
      vivo in NOD-SCID mice. The qualitative follow-up involved scanning electron
      microscopy (SEM) observations, live-dead assays, and histology. The cell amount
      was quantified by photon imager during 21 days in vitro and 2 months in vivo.
      Live- dead assay and SEM revealed that the cells survived after printing and
      spread onto PCL membranes. Circle-shaped patterns were maintained in vitro during
      the first week but they were no longer observable after 2 weeks, due to cell
      proliferation. Luciferase tracking displayed that the cell amount was increased
      in vitro and in vivo when the materials and the cells where stacked layer by
      layer. Histological sections of the in vivo samples revealed a thicker fibrous
      tissue in the layer-by-layer samples. We have demonstrated in this study that PCL
      electrospun biopapers can act as a shock-absorbing mattress for cell printing and
      could further support cell proliferation. The layer-by-layer printing provided an
      appropriate 3D environment for cell survival and enhanced cell proliferation in
      vitro and in vivo.

PMID- 21895564
TI  - Clinical effectiveness of Tyrophagus putrescentiae allergy by local nasal
      immunotherapy using strips of Dermatophagoides pteronyssinus.
AB  - BACKGROUND: House dust mites are a major source of aeroallergens for patients
      with allergic rhinitis and asthma. Most patients with allergic rhinitis are
      simultaneously sensitized by Dermatophagoides pteronyssinus (Dp) and Tyrophagus
      putrescentiae (Tp). Dp and Tp allergy in allergic rhinitis can be caused by cross
      reactivity, and the group 2 mite allergens appear to be the major cross-reactive
      allergens in mites. We previously demonstrated that local nasal immunotherapy
      (LNIT) with Dp-coated strips could modulate the serum levels of Dp-specific IgE.
      The aim of this study was to investigate whether Tp allergy could be modulated by
      LNIT with Dp. METHODS: Both Tyr p2-specific IgE in the sera and its effect on Tyr
      p2-triggered basophil histamine release (BHR) were measured to evaluate the Tp
      mediated allergic reaction before and after LNIT. RESULTS: The results showed
      that not only was Tyr p2-specific IgE reduced, but also Tyr p2-triggered
      histamine release in the sera after LNIT with Dp allergen strips. There was a
      significant reduction of Tyr p2-specific IgG1 and upregulation of IgG4 after LNIT
      with Dp allergen strips. When the amounts of histamine were compared between the
      two groups, rDer p2-triggering or rTyr p2-triggering histamine release was
      significantly reduced in the Dp treatment group compared with the normal saline
      treatment group. No matter in the rDer p2-triggering or rTyr p2-triggering
      histamine release, differences between before LNIT and after LNIT were
      statistically significant in the Dp group. CONCLUSION: Our study demonstrated
      that not only was Tyr p2-specific IgE reduced in the sera, but also its
      biological activity of Tyr p2-triggered BHR after LNIT with Dp strips. It is
      conceivable that the clinical effectiveness of Tp allergy by LNIT with Dp
      allergen strips may exist.

PMID- 21895565
TI  - Facile surface functionalization with glycosaminoglycans by direct coating with
      mussel adhesive protein.
AB  - The use of mussel adhesive proteins (MAPs) as a surface coating for cell adhesion
      has been suggested due to their unique properties of biocompatibility and
      effective adhesion on diverse inorganic and organic surfaces. The surface
      functionalization of scaffolds or implants using extracellular matrix (ECM)
      molecules is important for the enhancement of target cell behaviors such as
      proliferation and differentiation. In the present work, we suggest a new, simple
      surface functionalization platform based on the charge interactions between the
      positively charged MAP linker and negatively charged ECM molecules, such as
      glycosaminoglycans (GAGs). MAP was efficiently coated onto a titanium model
      surface using its adhesion ability. Then, several GAG molecules, including
      hyaluronic acid (HA), heparin sulfate (HS), chondroitin sulfate (CS), and
      dermatan sulfate (DS), were effectively immobilized on the MAP-coated surfaces by
      charge interactions. Using HA as a model GAG molecule, we found that the
      proliferation, spreading, and differentiation behaviors of mouse preosteoblast
      cells were all significantly improved on MAP/HA-layered titanium. In addition, we
      successfully constructed a multilayer film on a titanium surface with oppositely
      charged layer-by-layer coatings of MAP and HA. Collectively, our simple MAP-based
      surface functionalization strategy can be successfully used for the efficient
      surface immobilization of negatively charged ECM molecules in various tissue
      engineering and medical implantation applications.

PMID- 21895566
TI  - Occupation and COPD: a brief review.
AB  - BACKGROUND AND AIMS: This review summarizes the scientific literature relevant to
      occupational risk factors for chronic obstructive pulmonary disease (COPD).
      MATERIAL AND METHODS: This review emphasizes recent work in the field, while
      placing this in the context of two previous systematic reviews of the subject.
      RESULTS: Both the earlier summaries of the literature estimated that the
      population attributable risk percent (PAR%) of COPD linked to occupational
      exposures is approximately 15%. More recent studies also strongly support the
      association between workplace exposures and COPD. Among never smokers, the PAR%
      for work-related factors may approach 40%. Emerging data also indicate that
      occupational exposures, at a minimum, are additive to smoking-associated risk of
      COPD. CONCLUSIONS: The PAR% for work-related COPD is at least 15%. Scientific
      significance. The consistency, strength, and plausibility of these data support a
      causal relationship between occupational exposures and COPD.

PMID- 21895568
TI  - Representational pseudoneglect in an auditory-driven spatial working memory task.
AB  - Two experiments explored lateralized biases in mental representations of matrix
      patterns formed from aural verbal descriptions. Healthy participants listened,
      either monaurally or binaurally, to verbal descriptions of 6 by 3 matrix patterns
      and were asked to form a mental representation of each pattern. In Experiment 1,
      participants were asked to judge which half of the matrix, left or right,
      contained more filled cells and to rate the certainty of their judgement.
      Participants tended to judge that the left side was fuller than the right and
      showed significantly greater certainty when judging patterns that were fuller on
      the left. This tendency was particularly strong for left-ear presentation. In
      Experiment 2, participants conducted the same task as that in Experiment 1 but
      were also asked to recall the pattern for the side judged as fuller. Participants
      were again more certain in judging patterns that were fuller on the left
      particularly for left-ear presentation-but were no more accurate in remembering
      the details from the left. These results suggest that the left side of the mental
      representation was represented more saliently but it was not remembered more
      accurately. We refer to this lateralized bias as "representational
      pseudoneglect". Results are discussed in terms of theories of visuospatial
      working memory.

PMID- 21895569
TI  - Ambivalence, communication and past use: understanding what influences women's
      intentions to use contraceptives.
AB  - Unintended pregnancy among women in the 18-30 age group is a public health
      concern. The Extended Parallel Process Model (EPPM) provides a framework for
      exploring how women's perceptions of threat, efficacy, and fear influence
      intentions to use contraceptives. Past use and communication with best friends
      and partners were also considered. A telephone survey of 18-30-year-old women (N
      = 599) was completed. After univariate and bivariate analyses were conducted, the
      variables were entered into a hierarchal, multi-variate linear regression with
      three steps consistent with the EPPM to predict behavioral intention. The first
      step included the demographic variables of relationship status and income. The
      constructs for the EPPM were entered into step 2. Step 3 contained the fear
      measure. The model for the third step was significant, F(10,471) = 36.40, p <
      0.001 and the variance explained by this complete model was 0.42. Results suggest
      that perceived severity of the consequences of an unintended pregnancy (p <
      0.01), communication with friends (p < 0.01) and last sexual partner (p < 0.05),
      relationship status (p < 0.01), and past use (p < 0.001) were associated with
      women's intentions to use contraceptives. A woman's perception of the severity
      was related to her intention to use contraceptives. Half of the women (50.3%)
      reported ambivalence about the severity of an unintended pregnancy. In our study,
      talking with their last sexual partner had a positive effect on intentions to use
      contraceptives, while talking with friends influenced intentions in a negative
      direction. These results reconfirm the need for public health practitioners and
      health care providers to consider level of ambivalence toward unintended
      pregnancy, communication with partner, and relationship status when trying to
      improve women's contraceptive behaviors. Implications for effective communication
      interventions are discussed.

PMID- 21895567
TI  - A quantitative risk assessment of multiple factors influencing HIV/AIDS
      transmission through unprotected sex among HIV-seropositive men.
AB  - The objective of this study is to conduct a quantitative risk assessment of
      multiple factors influencing HIV/AIDS transmission through unprotected sexual
      practices among HIV-seropositive men. A knowledgebase was developed by reviewing
      different published sources. The data were collected from different sources
      including Centers for Disease Control and Prevention, selected journals, and
      reports. The risk pathway scenario tree was developed based on a comprehensive
      review of published literature. The variables are organized into nine major
      parameter categories. Monte Carlo simulations for the quantitative risk
      assessment of HIV/AIDS transmission was executed with the software @Risk 4.0
      (Palisade Corporation). Results show that the value for the likelihood of
      unprotected sex due to having less knowledge about HIV/AIDS and negative attitude
      toward condom use and safer sex ranged from 1.24 * 10(-5) to 8.47 * 10(-4) with
      the mean and standard deviation of 1.83 * 10(-4) and 8.63 * 10(-5), respectively.
      The likelihood of unprotected sex due to having greater anger-hostility, anxiety,
      less satisfied with aspects of life, and greater depressive symptoms ranged from
      2.76 * 10(-9) to 5.34 * 10(-7) with the mean and standard deviation of 5.23 * 10(
      8) and 3.58 * 10(-8), respectively. The findings suggest that HIV/AIDS research
      and intervention programs must be focused on behavior, and the broader setting
      within which individual risky behaviors occur.

PMID- 21895570
TI  - Longitudinal associations between children's understanding of emotions and theory
      of mind.
AB  - Theory of mind competence and knowledge of emotions were studied longitudinally
      in a sample of preschoolers aged 3 (n=263) and 4 (n=244) years. Children were
      assessed using standard measures of theory of mind and emotion knowledge. Three
      competing hypotheses were tested regarding the developmental associations between
      children's theory of mind abilities and their knowledge of emotions. First, that
      an understanding of emotion develops early and informs children's understanding
      of others' thinking. Alternatively, having a basic theory of mind may help
      children learn about emotions. Third, that the two domains are separate aspects
      of children's social cognitive skills such that each area develops independently.
      Results of hierarchical regressions supported the first hypothesis that early
      emotion understanding predicts later theory-of-mind performance, and not the
      reverse.

PMID- 21895571
TI  - Autobiographical memory characteristics in depression vulnerability: formerly
      depressed individuals recall less vivid positive memories.
AB  - The differential activation hypothesis (DAH; Teasdale, 1988) proposes that
      individuals who are vulnerable to depression can be distinguished from non
      vulnerable individuals by the degree to which negative thoughts and maladaptive
      cognitive processes are activated during sad mood. While retrieval of negative
      autobiographical memories is noted as one such process, the model does not
      articulate a role for deficits in recalling positive memories. Two studies were
      conducted to compare the autobiographical memory characteristics of never
      depressed and formerly depressed individuals following a sad mood induction. In
      Study 1, features of negative memories of never-depressed and formerly depressed
      individuals did not differ, either in neutral or sad mood. For positive memories,
      groups did not differ in neutral mood, but following a sad mood induction,
      formerly depressed individuals rated their positive memories as less vivid than
      their never-depressed counterparts. Study 2 examined positive autobiographical
      memory features more comprehensively and replicated the finding that in a sad
      mood formerly depressed individuals recalled less vivid positive memories than
      never-depressed controls. These findings suggest that the phenomenological
      features of positive memories could represent an important factor in depressive
      vulnerability, and, more broadly, that depression may be associated with a
      deficit in the processing of positive material.

PMID- 21895573
TI  - Cultural grounding of regret: regret in self and interpersonal contexts.
AB  - The purpose of this study was to explore cultural similarities and differences in
      regret, focusing on distinctions between interpersonal and self-situations, and
      between action and inaction regrets. Japanese and American undergraduates were
      asked to describe regrets experienced in interpersonal and self-situations. We
      found that both situational and cultural contexts influenced the likelihood of
      regretting inactions over actions. Participants were more likely to recall
      inaction regrets in self-situations than in interpersonal situations, and that
      the likelihood of recalling inaction regrets was more pronounced for Americans
      than for Japanese. Furthermore, we examined the intensity of the regret. Whereas
      American students experienced regret as intense as that of Japanese students in
      self-situations, Japanese students experienced regret more strongly than American
      students in interpersonal situations. Detailed content analysis also showed that
      individuals experienced regret in ways consistent with cultural values. The
      situational and cultural grounding of regret is discussed.

PMID- 21895574
TI  - Unintentional preparation of motor impulses after incidental perception of need
      rewarding objects.
AB  - Using a new method, we examined whether incidental perception of need-rewarding
      (positive) objects unintentionally prepares motor action. Participants who varied
      in their level of need for water were presented with glasses of water (and
      control objects) that were accompanied by go and no-go cues that required a
      response (key-press) or withholding a response. Importantly, if need-rewarding
      objects unintentionally prepare action, presentation of no-go cues should lead to
      motor inhibition of these prepared motor impulses. Consistent with this
      hypothesis, results showed that participants relatively high in need for water
      (and hence, who perceive water as a rewarding, positive object) were slower to
      react to a successive action probe after withholding a response during perception
      of water than during perception of the control object, suggesting motor
      inhibition of unintentionally prepared motor impulses. We propose that incidental
      perception of need-rewarding objects unintentionally potentiates preparation of
      motor action to these objects.

PMID- 21895572
TI  - Children's 5-HTTLPR genotype moderates the link between maternal criticism and
      attentional biases specifically for facial displays of anger.
AB  - Theorists have proposed that negative experiences in childhood may contribute to
      the development of experience-specific information-processing biases, including
      attentional biases. There are also clear genetic influences on cognitive
      processes, with evidence that polymorphisms in specific candidate genes may
      moderate the impact of environmental stress on attentional biases (e.g., a
      functional polymorphism in the serotonin transporter gene; 5-HTTLPR). In the
      current study, we tested a gene*environment (G*E) model of risk for attentional
      biases. We hypothesised that children whose mothers exhibit high levels of
      expressed emotion criticism (EE-Crit) would display attentional biases
      specifically for angry, but not happy or sad, faces, and that this link would be
      stronger among children carrying one or two copies of the 5-HTTLPR short allele
      than among those homozygous for the long allele. Results generally supported
      these hypotheses, though we found that carriers of the 5-HTTLPR short allele who
      also had a critical mother exhibited attentional avoidance of angry faces rather
      than preferential attention.

PMID- 21895575
TI  - How do social fears in adolescence develop? Fear conditioning shapes attention
      orienting to social threat cues.
AB  - Social fears emerging in adolescence can have negative effects on emotional well
      being. Yet the mechanisms by which these risks occur are unknown. One possibility
      is that associative learning results in fears to previously neutral social
      stimuli. Such conditioned responses may alter subsequent processing of social
      stimuli. We used a novel conditioning task to examine how associative processes
      influence social fear and attention orienting in adolescents. Neutral photographs
      were paired with socially rewarding or aversive stimuli during conditioning; a
      dot-probe task then assessed biases in attention orienting. The social
      conditioning task modified subjective ratings of the neutral stimuli. Moreover,
      for the neutral stimulus that was paired with the aversive stimulus, the strength
      of conditioning showed a relationship with subsequent attentional vigilance. The
      findings elucidate mechanisms by which negative peer experiences during
      adolescence may affect emotional processing.

PMID- 21895576
TI  - CTCF function is modulated by neighboring DNA binding factors.
AB  - The zinc-finger protein CTCF was originally identified in the context of gene
      silencing and gene repression (Baniahmad et al. 1990; Lobanenkov et al. 1990).
      CTCF was later shown to be involved in several transcriptional mechanisms such as
      gene activation (Vostrov et al. 2002) and enhancer blocking (Filippova et al.
      2001; Hark et al. 2000; Kanduri et al. 2000; Lutz et al. 2003; Szabo et al. 2000;
      Tanimoto et al. 2003; Phillips and Corces 2009; Bell et al. 1999; Zlatanova and
      Caiafa 2009a, 2009b). Insulators block the action of enhancers when positioned
      between enhancer and promoter. CTCF was found to be required in almost all cases
      of enhancer blocking tested in vertebrates. This CTCF-mediated enhancer blocking
      is in many instances conferred by constitutive CTCF action. For some examples
      however, a modulation of the enhancer blocking activity was documented (Lutz et
      al. 2003; Weth et al. 2010). One mechanism is achieved by regulation of binding
      to DNA. It was shown that CTCF is not able to bind to those binding-sites
      containing methylated CpG sequences. At the imprinting control region (ICR) of
      the Igf2/H19 locus the binding-site for CTCF on the paternal allele is
      methylated. This prevents DNA-binding of CTCF, resulting in the loss of enhancer
      blocking (Bell and Felsenfeld 2000; Chao et al. 2002; Filippova et al. 2001; Hark
      et al. 2000; Kanduri et al. 2000, 2002; Szabo et al. 2000; Takai et al. 2001).
      Not only can DNA methylation interfere with CTCF binding to DNA, it was also
      shown in one report that RNA transcription through the CTCF binding site results
      in CTCF eviction (Lefevre et al. 2008).   In contrast to these cases most of the
      DNA sites are not differentially bound by CTCF. Even CTCF interaction with its
      cofactor cohesin does not seem to differ in different cell types (Schmidt et al.
      2010). These results indicate that regulation of CTCF activity might be achieved
      by neighboring factors bound to DNA. In fact, whole genome analyses of CTCF
      binding sites identified several classes of neighboring sequences (Dickson et al.
      2010; Boyle et al. 2010; Essien et al. 2009). Therefore, in this review we will
      summarize those results for which a combined action of CTCF with factors bound
      adjacently was found. These neighboring factors include the RNA polymerases I, II
      and III, another zinc finger factor VEZF1 and the factors YY1, SMAD, TR and Oct4.
      Each of these seems to influence, modulate or determine the function of CTCF.
      Thereby, at least some of the pleiotropic effects of CTCF can be explained.

PMID- 21895577
TI  - Renovation and renewal.

PMID- 21895578
TI  - Medicolegal aspects of the third wave of asbestos-related disease in Australia.

PMID- 21895580
TI  - Hendra virus.

PMID- 21895579
TI  - Minimising the misuse of oxycodone and other pharmaceutical opioids in Australia.

PMID- 21895581
TI  - Why the tobacco industry fears plain packaging.

PMID- 21895582
TI  - Should more Australian doctors be salaried than paid by fee-for-service? - Yes.

PMID- 21895583
TI  - Should more Australian doctors be salaried than paid by fee-for-service? - No.

PMID- 21895584
TI  - PatientsLikeMe and the tale of three brothers.

PMID- 21895585
TI  - Is it time to commence newborn screening for congenital adrenal hyperplasia in
      Australia?
AB  - 21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal
      hyperplasia, with an incidence of 1:14000 live births and equal prevalence among
      males and females. Newborns with the most severe "salt-wasting" form of 21-OHD
      are susceptible to salt-wasting crises in the first few weeks of life. This is
      associated with morbidity and mortality. 21-OHD newborn screening (NBS) is
      currently performed in many countries. Despite several prominent medical
      societies recommending 21-OHD NBS, no state in Australia currently screens for
      this condition. We report a case that illustrates the need to reconsider
      including 21-OHD in NBS. 21-OHD NBS can be reliable, sensitive and effective in
      reducing morbidity and mortality.

PMID- 21895586
TI  - A no-fault compensation scheme for serious adverse events attributed to
      vaccination.

PMID- 21895587
TI  - What does the future hold for general medicine? Comment.

PMID- 21895588
TI  - Should opioids be used for chronic non-cancer pain?

PMID- 21895589
TI  - Bipartisan support for Australia's supervised injecting facility: a decade in the
      making.

PMID- 21895590
TI  - How can Australia do better for Indigenous health?

PMID- 21895591
TI  - Development of clinical-quality registries in Australia: the way forward.

PMID- 21895592
TI  - Predictive validity of the Undergraduate Medicine and Health Sciences Admission
      Test for medical students' academic performance.

PMID- 21895593
TI  - Hospital and emergency department use in the last year of life: a baseline for
      future modifications to end-of-life care.

PMID- 21895594
TI  - Contrast induced nephropathy in patients with pre-existing renal impairment
      undergoing invasive coronary procedures - a long-term follow-up.

PMID- 21895595
TI  - The impact of potential new diagnostic criteria on the prevalence of gestational
      diabetes mellitus in Australia.

PMID- 21895596
TI  - Increasing incidence of malignant mesothelioma after exposure to asbestos during
      home maintenance and renovation.
AB  - OBJECTIVE: To determine trends in incidence of malignant mesothelioma (MM) caused
      by exposure to asbestos during home maintenance and renovation. DESIGN, SETTING
      AND PARTICIPANTS: Using the Western Australian Mesothelioma Register, we reviewed
      all cases of MM diagnosed in WA from 1960 to the end of 2008, and determined the
      primary source of exposure to asbestos. Categories of exposure were collapsed
      into seven groups: asbestos miners and millers from Wittenoom; all other asbestos
      workers; residents from Wittenoom; home maintenance/renovators; other people
      exposed but not through their occupation; and people with unknown asbestos
      exposure; or no known asbestos exposure. Latency periods and age at diagnosis for
      each group were calculated and compared. RESULTS: In WA, 1631 people (1408 men,
      223 women) were diagnosed with MM between 1960 and 2008. Since 1981, there have
      been 87 cases (55 in men) of MM attributed to asbestos exposure during home
      maintenance and renovation, and an increasing trend in such cases, in both men
      and women. In the last 4 years of the study (2005-2008), home renovators
      accounted for 8.4% of all men and 35.7% of all women diagnosed with MM. After
      controlling for sex and both year and age at diagnosis, the latency period for
      people exposed to asbestos during home renovation was significantly shorter than
      that for all other exposure groups, but the shorter follow-up and difficulty
      recalling when exposure first occurred in this group may partly explain this.
      CONCLUSIONS: MM after exposure to asbestos during home renovation is an
      increasing problem in WA, and these cases seem to have a shorter latency period
      than other types of exposure. MM cases related to renovation will probably
      continue to increase because of the many homes that have contained, and still
      contain, asbestos building products.

PMID- 21895597
TI  - Reusable venesection tourniquets: a potential source of hospital transmission of
      multiresistant organisms.
AB  - OBJECTIVE: To determine the prevalence of multiresistant organism (MRO)
      colonisation of reusable venesection tourniquets. DESIGN AND SETTING: A
      prospective study in a tertiary hospital to collect and analyse reusable
      venesection tourniquets for the presence of MROs - methicillin-resistant
      Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and
      extended-spectrum beta-lactamase and metallo-beta-lactamase-producing
      Enterobacteriaceae - using a sensitive enrichment method. Tourniquets were
      collected and tested during a 10-week period between September and November 2010.
      MAIN OUTCOME MEASURE: Prevalence of MRO colonisation of tourniquets. RESULTS: The
      overall colonisation rate of 100 tourniquets randomly collected from general
      wards, ambulatory care areas and critical care areas was 78%. MROs were isolated
      from 25 tourniquets collected from a variety of hospital locations, including
      general wards, the intensive care unit, burns unit and anaesthetic bay. MRSA was
      isolated from 14 tourniquets and VRE from 19; both MRSA and VRE were isolated
      from nine tourniquets. There were no microorganisms isolated from 22 tourniquets.
      CONCLUSION: Reusable tourniquets can be colonised with MROs and may be a
      potential source of transmission of MROs to hospitalised patients.

PMID- 21895598
TI  - Prescription of opioid analgesics and related harms in Australia.
AB  - OBJECTIVE: To document trends in: (i) prescribing of morphine and oxycodone; (ii)
      hospital separations for overdose; (iii) presentations for treatment of problems
      associated with these drugs; and (iv) oxycodone-related mortality data in
      Australia. DESIGN AND SETTING: Cross-sectional study analysing prescriptions for
      morphine and oxycodone based on figures adjusted using Australian Bureau of
      Statistics estimated resident population and prospectively collected data from:
      (i) the National Hospital Morbidity Database on hospital separations primarily
      attributed to poisoning with opioids other than heroin ("other opioids"); (ii)
      the Alcohol and Other Drug Treatment National Minimum Data Set for treatment
      episodes where morphine or oxycodone were the primary or other drugs of concern;
      (iii) the National Coronial Information System on deaths where oxycodone was the
      underlying cause of death or a contributory factor. MAIN OUTCOME MEASURES:
      Population-adjusted numbers of (i) prescriptions for morphine and oxycodone by 10
      year age group, (ii) hospital separations for "other opioid" poisoning, and (iii)
      treatment episodes related to morphine or oxycodone; and (iv) number of oxycodone
      related deaths. RESULTS: Prescriptions for morphine declined, while those for
      oxycodone increased. Prescriptions for both were highest among older Australians.
      Hospital separations for "other opioid" poisoning doubled between the financial
      years 2005-06 and 2006-07. Treatment episodes for morphine remained stable, while
      those for oxycodone increased. There were 465 oxycodone-related deaths recorded
      during 2001-2009. CONCLUSIONS: Oxycodone prescriptions in Australia have
      increased, particularly among older Australians. The increase may, in part,
      reflect appropriate prescribing for pain among an ageing population. However we
      are unable to differentiate non-medical use from appropriate prescribing from
      this data. In comparison to heroin, the morbidity and mortality associated with
      oxycodone is relatively low in Australia. There is a continued need for
      comprehensive training of general practitioners in assessing patients with
      chronic non-malignant pain and prescribing of opioids for these patients, to
      minimise the potential for harms associated with use of these medications.

PMID- 21895599
TI  - Tunnel vision and night blindness in a 52-year-old man.

PMID- 21895600
TI  - Harlequin syndrome after jogging.

PMID- 21895605
TI  - VEGF increases the proliferative capacity and eNOS/NO levels of endothelial
      progenitor cells through the calcineurin/NFAT signalling pathway.
AB  - We have investigated whether VEGF (vascular endothelial growth factor) regulates
      the proliferative capacity and eNOS (endothelial nitric oxide synthase)/NO
      (nitric oxide) pathway of EPCs (endothelial progenitor cells) by activating CaN
      (calcineurin)/NFAT (nuclear factor of activated T-cells) signalling. EPCs were
      obtained from cultured mononuclear cells isolated from the peripheral blood of
      healthy adults. Treatment with VEGF (50 ng/ml) potently promoted CaN enzymatic
      activity, activation of NFAT2, cell proliferation, eNOS protein expression and NO
      production. Pretreatment with cyclosporin A (10 MUg/ml), a pharmacological
      inhibitor of CaN or 11R-VIVIT, a special inhibitor of NFAT, completely abrogated
      the aforementioned effects of VEGF treatment and increased apoptosis. The results
      indicate that VEGF treatment promotes the proliferative capacity of human EPCs by
      activating CaN/NFAT signalling leading to increased eNOS protein expression and
      NO production.

PMID- 21895606
TI  - AP-1 and NF-kappaB transcriptionally regulate interleukin-8 in EA.Hy926 cells
      under shear stress.
AB  - Cardiovascular and cerebrovascular diseases remain the leading cause of death in
      the world. AS (atherosclerosis) is not only an inflammatory disease in which
      chemokines play the main role but also a disorder that is related to blood SS
      (shear stress). We have investigated the action of IL-8 (interleukin-8) mRNA
      expression in human endothelial cells line-EA.Hy926 under SS at different
      intensities and duration. Expression increases with time in an intensity
      dependent manner. With regard to the transcriptional mechanism involved,
      transient transfection of the human wild-type IL-8 promoter (-162/+44)/luciferase
      reporter plasmid, or site mutation of one of the binding sites [AP-1 (activator
      protein 1) or NF-kappaB (nuclear factor kappaB)] in the IL-8 promoter region was
      investigated. Both AP-1 and NF-kappaB were essential for SS-activated
      transcription, with the cells responding to NF-kappaB activation within minutes.
      After stimulated at low SS (4.20 dyne/cm2) for 30 min, the P65 subunit was
      translocated from the cytoplasm to nucleus for at least 60 min, while the
      cytoplasmic level of IkappaB (inhibitory kappaB) gradually decreased. The
      combined activation of NF-kappaB and AP-1 are the upstream regulators of low SS
      induced IL-8 production in EA.Hy926 cells, which subsequently trigger an
      inflammatory reaction in endothelium.

PMID- 21895608
TI  - Intracellular curvature-generating proteins in cell-to-cell fusion.
AB  - Cell-to-cell fusion plays an important role in normal physiology and in different
      pathological conditions. Early fusion stages mediated by specialized proteins and
      yielding fusion pores are followed by a pore expansion stage that is dependent on
      cell metabolism and yet unidentified machinery. Because of a similarity of
      membrane bending in the fusion pore rim and in highly curved intracellular
      membrane compartments, in the present study we explored whether changes in the
      activity of the proteins that generate these compartments affect cell fusion
      initiated by protein fusogens of influenza virus and baculovirus. We raised the
      intracellular concentration of curvature-generating proteins in cells by either
      expressing or microinjecting the ENTH (epsin N-terminal homology) domain of epsin
      or by expressing the GRAF1 (GTPase regulator associated with focal adhesion
      kinase 1) BAR (Bin/amphiphysin/Rvs) domain or the FCHo2 (FCH domain-only protein
      2) F-BAR domain. Each of these treatments promoted syncytium formation. Cell
      fusion extents were also influenced by treatments targeting the function of
      another curvature-generating protein, dynamin. Cell-membrane-permeant inhibitors
      of dynamin GTPase blocked expansion of fusion pores and dominant-negative mutants
      of dynamin influenced the syncytium formation extents. We also report that
      syncytium formation is inhibited by reagents lowering the content and
      accessibility of PtdIns(4,5)P(2), an important regulator of intracellular
      membrane remodelling. Our findings indicate that fusion pore expansion at late
      stages of cell-to-cell fusion is mediated, directly or indirectly, by
      intracellular membrane-shaping proteins.

PMID- 21895609
TI  - Thermodynamics and structural analysis of positive allosteric modulation of the
      ionotropic glutamate receptor GluA2.
AB  - Positive allosteric modulators of the ionotropic glutamate receptor-2 (GluA2) are
      promising compounds for the treatment of cognitive disorders, e.g. Alzheimer's
      disease. These modulators bind within the dimer interface of the LBD (ligand
      binding domain) and stabilize the agonist-bound conformation slowing receptor
      desensitization and/or deactivation. In the present study, we employ isothermal
      titration calorimetry to determine binding affinities and thermodynamic details
      of binding of modulators of GluA2. A mutant of the LBD of GluA2 (LBD-L483Y-N754S)
      that forms a stable dimer in solution was used. The potent GluA2 modulator BPAM
      97 was used as a reference compound. Evidence that BPAM-97 binds in the same
      pocket as the well-known GluA2 modulator cyclothiazide was obtained from X-ray
      structures. The LBD-L483Y-N754S:BPAM-97 complex has a Kd of 5.6 MUM (DeltaH=-4.9
      kcal/mol, -TDeltaS=-2.3 kcal/mol; where 1 kcal~4.187 kJ). BPAM-97 was used in a
      displacement assay to determine a Kd of 0.46 mM (DeltaH=-1.2 kcal/mol, -TDeltaS=
      3.3 kcal/mol) for the LBD-L483Y-N754S:IDRA-21 complex. The major structural
      factors increasing the potency of BPAM-97 over IDRA-21 are the increased van der
      Waals contacts to, primarily, Met496 in GluA2 imposed by the ethyl substituent of
      BPAM-97. These results add important information on binding affinities and
      thermodynamic details, and provide a new tool in the development of drugs against
      cognitive disorders.

PMID- 21895610
TI  - Anthropometric measurements as predictors of cephalopelvic disproportion: Can the
      diagnostic accuracy be improved?
AB  - OBJECTIVE: We assessed the efficacy of maternal anthropometric measurements and
      clinical estimates of fetal weight in isolation and in combination as predictors
      of cephalopelvic disproportion (CPD). DESIGN: Prospective cohort study. SETTING:
      Tertiary care teaching hospital, two affiliated hospitals with facilities for
      conducting cesarean delivery and seven affiliated primary care facilities with no
      operation theaters. SAMPLE: Primigravidae over 37 weeks' gestation attending
      these facilities during a 20-month period with a singleton pregnancy in vertex
      presentation. METHODS: Several anthropometric measurements were taken in 249
      primigravidae. Fetal weight was estimated. Differences in these measurements
      between the vaginal delivery and CPD groups were analyzed. The validity of these
      measurements in predicting CPD was analyzed by plotting receiver operating
      characteristic curves and by logistic regression analysis. MAIN OUTCOME MEASURE:
      Mode of delivery. RESULTS: Maternal height, foot size, inter-trochanteric
      diameter and bis-acromial diameter showed the highest positive predictive values
      for CPD. Combining some maternal measurements with estimates of fetal weight
      increased predictive values modestly, which are likely to be greater if the
      estimates of fetal weight are close to the actual birth weight. Based on
      multivariate analysis the risk factors for CPD in our population were foot length
      <=23cm, inter-trochanteric diameter <=30cm and estimated fetal weight >=3 000g.
      CONCLUSIONS: Maternal anthropometric measurements can predict CPD to some extent.
      Combining maternal measurements with clinical estimates of fetal weight only
      enhances the predictive value to a relatively modest degree (positive predictive
      value 24%).

PMID- 21895607
TI  - Targeting VIP and PACAP receptor signalling: new therapeutic strategies in
      multiple sclerosis.
AB  - MS (multiple sclerosis) is a chronic autoimmune and neurodegenerative pathology
      of the CNS (central nervous system) affecting approx. 2.5 million people
      worldwide. Current and emerging DMDs (disease-modifying drugs) predominantly
      target the immune system. These therapeutic agents slow progression and reduce
      severity at early stages of MS, but show little activity on the neurodegenerative
      component of the disease. As the latter determines permanent disability, there is
      a critical need to pursue alternative modalities. VIP (vasoactive intestinal
      peptide) and PACAP (pituitary adenylate cyclase-activating peptide) have potent
      anti-inflammatory and neuroprotective actions, and have shown significant
      activity in animal inflammatory disease models including the EAE (experimental
      autoimmune encephalomyelitis) MS model. Thus, their receptors have become
      candidate targets for inflammatory diseases. Here, we will discuss the
      immunomodulatory and neuroprotective actions of VIP and PACAP and their
      signalling pathways, and then extensively review the structure-activity
      relationship data and biophysical interaction studies of these peptides with
      their cognate receptors.

PMID- 21895611
TI  - Combined ultrasound and biochemistry for risk evaluation in the first trimester:
      the Stockholm experience of a new web-based system.
AB  - OBJECTIVE: To evaluate the performance of a new first trimester web-based
      software for the detection of chromosomal anomalies using a combination of
      ultrasound and biochemistry. DESIGN: Registry-based cohort study. SETTING:
      Ultrasound units in the Stockholm region. POPULATION: 20 710 women with singleton
      pregnancies were examined at 11(+0) to 13(+6) weeks' gestational age during a
      three-year period 2006-2009. METHODS: The risks for trisomy 21, 13 and 18 were
      calculated using a combination of maternal age, serum markers and nuchal
      translucency. Individual risk estimates were calculated and then reported to a
      web-based system using a new algorithm based on likelihood ratios of each marker
      derived from Gaussian distributions in normal and affected pregnancies. MAIN
      OUTCOME MEASURES: The impact on rates of invasive testing and the incidence of
      children born with Down's syndrome after implementing the method. RESULTS:
      Approximately a third of all pregnant women in the region were examined with the
      combined test. The detection and test positive rates for Down's syndrome was 90
      and 6.8%, respectively. Invasive testing among pregnant women decreased from 15
      to 8% after introducing the method but the incidence of children born with Down's
      syndrome did not decrease during the study period. CONCLUSION: The new web-based
      software is an effective method for the detection of trisomy 21 with similar
      performance compared to other programs. However, it needs to be offered to all
      pregnant women to have an impact on the incidence of Down's syndrome.

PMID- 21895612
TI  - Platelet antibodies and fetal growth: maternal antibodies against fetal platelet
      antigen 1a are strongly associated with reduced birthweight in boys.
AB  - OBJECTIVE: To assess whether maternal HPA 1a alloimmunization is associated with
      birthweight. DESIGN: A retrospective observational cohort study. SETTING: The
      national reference laboratory for clinical platelet immunology at a university
      hospital. POPULATION: 165 HPA 1a incompatible pregnancies identified from a
      recent screening study of 100 448 women (124 pregnancies) and the national
      reference laboratory for clinical platelet immunology (41 pregnancies). METHODS:
      A linear mixed model analysis was used to assess whether maternal anti-HPA 1a
      antibodies were associated with birthweight. A generalized linear model was used
      to assess maternal anti-HPA 1a antibodies as risk factor for small-for
      gestational age neonates. Both models were adjusted for gestational age at time
      of delivery, maternal age, parity, smoking habits during pregnancy, preeclampsia,
      diabetes mellitus and fetal sex. MAIN OUTCOME MEASURES. Maternal anti-HPA 1a
      antibody as risk factor of reduced birthweight and small-for-gestational age
      neonates. RESULTS: The level of maternal anti-HPA 1a antibodies was significantly
      associated with birthweight and risk of small-for-gestational age neonates after
      correcting for confounding variables (p<0.001). However, this association was
      only significant for boys. When the mother had high levels of anti-HPA 1a
      antibodies during pregnancy, the adjusted mean birthweight in boys was 530g lower
      compared with anti-HPA 1a antibody negative pregnancies (p<0.001). CONCLUSIONS: A
      linear relation between maternal anti-HPA 1a antibody levels and reduced
      birthweight in boys was demonstrated. Reduced birthweight should be considered a
      possible complication of fetal and neonatal alloimmune thrombocytopenia.

PMID- 21895613
TI  - Long-term outcome of porcine skin graft in surgical treatment of recurrent pelvic
      organ prolapse. An open randomized controlled multicenter study.
AB  - OBJECTIVE: To determine the long-term objective and subjective outcomes of use of
      a porcine skin graft (Pelvicol) compared with conventional colporrhaphy in
      recurrent pelvic organ prolapse surgery and to analyze risk factors and safety.
      DESIGN: Open randomized controlled multicenter study. SETTING: Eight Swedish
      hospitals. POPULATION: 135 consecutive women with recurrent cystocele and/or
      rectocele admitted for vaginal prolapse surgery; 132 completed the study, 64 were
      randomly allocated to receive conventional colporrhaphy and 68 to Pelvicol.
      METHODS: Conventional anterior and posterior colporrhaphy and colporrhaphy with
      use of Pelvicol mesh reinforcement. Clinical evaluation by means of pelvic organ
      prolapse quantification (POP-Q) and symptom questionnaire preoperatively, three
      months and three years postoperatively. MAIN OUTCOME MEASURES: Anatomical and
      subjective outcome. Recurrence was defined as POP-Q >= stage 2. RESULTS: At three
      month follow-up, early recurrence/surgical failures occurred significantly more
      often in the Pelvicol group, but at the three-year follow-up the recurrence rates
      were similar. The recurrence rates in the anterior compartment were 57-62% and 44
      23% in the posterior compartment for the colporrhaphy and Pelvicol groups,
      respectively. Symptoms were substantially and equally reduced in the two groups
      after surgery. Sexual activity and function did not seem to be affected adversely
      in any group. The complication rate was low. Risk factors for anatomical
      recurrence were age, body mass index and preoperative stage of the prolapse.
      CONCLUSIONS: With the surgical technique used in this study, Pelvicol did not
      provide advantages over conventional colporrhaphy in recurrent pelvic organ
      prolapse concerning anatomical and subjective outcomes.

PMID- 21895614
TI  - First trimester prediction of small- and large-for-gestation neonates by an
      integrated model incorporating ultrasound parameters, biochemical indices and
      maternal characteristics.
AB  - OBJECTIVE: To identify maternal/pregnancy characteristics, first trimester
      ultrasound parameters and biochemical indices which are significant independent
      predictors of small-for-gestational age (SGA) and large-for-gestational age (LGA)
      neonates. DESIGN: Retrospective cross-sectional study. SETTING: Two fetal
      Medicine Units. POPULATION: 4 702 singleton pregnancies presenting for screening
      for chromosomal abnormalities by nuchal translucency and maternal serum
      biochemistry at 11-14 weeks. METHODS: Reference ranges for birthweight applied to
      our population were constructed by the Royston and Wright method. Multiple
      logistic regression was applied to develop first trimester prediction models for
      SGA and LGA. MAIN OUTCOME MEASURES: Birth of SGA or LGA neonate. RESULTS:
      Maternal height, parity, smoking, assisted conception, delta crown-rump length,
      delta nuchal translucency, free beta human chorionic gonadotrophin and pregnancy
      associated plasma protein-A were significant independent predictors of SGA.
      Maternal weight and height, smoking, delta crown-rump length and delta nuchal
      translucency were significant independent predictors of LGA. Models for SGA
      (AUC=0.7296, CI: 0.69-0.76, p<0.0001) and LGA (AUC=0.6901, CI: 0.65-0.72,
      p<0.0001) were derived, applicable to routine obstetric population at low risk
      for these conditions. For 20% screen positive rate the modeling achieves
      sensitivities of about 55% for SGA and 48% for LGA neonates. CONCLUSION:
      Prediction for birthweight deviations is feasible using data available at the
      routine 11-14 weeks' examination. Delta CRL and delta nuchal translucency were
      significant independent predictors for both SGA and LGA.

PMID- 21895615
TI  - Mass ligation: M cross double ligation with the edge picked up.

PMID- 21895616
TI  - Mammalian target of rapamycin (mTOR) inhibitors slow skin carcinogenesis, but
      impair wound healing.
AB  - BACKGROUND: Recent studies suggest that patients on mammalian target of rapamycin
      (mTOR) inhibitors experience a reduction in cutaneous carcinogenesis by an
      estimated 50% or more compared with calcineurin inhibitors. While randomized
      trials are running, organ transplant recipients are frequently switched from
      calcineurin inhibitors to mTOR inhibitors when cutaneous carcinogenesis
      increases. OBJECTIVES: To slow carcinogenesis in our patient, a heart transplant
      recipient with a neuropathic diabetic foot syndrome who had developed cutaneous
      carcinogenesis at a rate of more than 20 squamous cell carcinomas (SCC) annually.
      METHODS: The patient's immunosuppression was switched from the calcineurin
      inhibitor ciclosporin to the mTOR inhibitor everolimus. RESULTS: Carcinogenesis
      slowed to six SCC annually; however, he developed recalcitrant diabetic foot
      ulcers which were purely neuropathic and nonangiopathic, and a limb-threatening
      fistulating necrotic erysipelas of the right leg. Both sites responded poorly to
      antibiotic therapy, offloading and debridement. This skin fistula became chronic
      and some toes were at risk for minor amputation. In view of the propensity for
      mTOR inhibitors to impair would healing, immunosuppression was switched back to
      ciclosporin. All wounds healed rapidly, but skin carcinogenesis rose to former
      levels. CONCLUSIONS: This case impressively illustrates the clinical dilemma for
      mTOR inhibitor use where benefit in carcinogenesis is counterbalanced by
      impairment in wound healing. Changes in immunosuppressive regimens should thus be
      made on an individual basis with careful consideration of the relative risks.

PMID- 21895617
TI  - Nutritional outcome in children with severe generalized recessive dystrophic
      epidermolysis bullosa: a short- and long-term evaluation of gastrostomy and
      enteral feeding.
AB  - BACKGROUND: Generalized recessive dystrophic epidermolysis bullosa (RDEB) is
      often complicated by high nutritional difficulties with risks of malnutrition.
      OBJECTIVES: To provide information regarding the benefits of enteral feeding by
      gastrostomy (GTF), energy and protein requirements, tolerance, growth and
      pubertal development in children with RDEB. METHODS: Twenty-four patients were
      referred over a 7-year period in a retrospective study. Gastrostomy placement was
      decided in patients unable to feed orally and/or presenting loss in weight and
      height of at least 1 SD compared with their best growth level, despite regular
      nutritional advice. Weight and height were expressed as Z-scores. Catch-up growth
      following GTF onset was studied. RESULTS: Gastrostomies were performed in 11
      children (aged 9.0+/-5.8years), and one young man aged 18years. The body weight Z
      score was -2.3+/-1.0, height Z-score 1.1+/-1.1, weight-for-height was 81+/-11%
      and height-for-age 95+/- 4%. At onset, GTF provided 74+/-21% and 180+/-81% of the
      recommended dietary allowance (RDA) for energy and proteins, respectively. At
      study update (53+/-20months), GTF provided 91+/-29% and 205+/-100% of RDA for
      energy and proteins, respectively. Weight-for-height reached 92+/-15% and height
      for-age 98+/-5%. A normal puberty was obtained when GT was performed before the
      age of 10years. Skin was not improved. CONCLUSION: Malnutrition was observed in
      50% of the children with generalized RDEB. Protein and energy needs are
      particularly high. GTF is well tolerated and helps with catch-up growth and
      puberty. It must be considered before malnutrition onset, and, if necessary,
      before puberty.

PMID- 21895618
TI  - Molecular genetic support for the rule of dichotomy in type 2 segmental Darier
      disease.

PMID- 21895619
TI  - Bathing suit ichthyosis with summer exacerbation: a temperature-sensitive case.

PMID- 21895620
TI  - Incidence, cancer risk and mortality of dermatomyositis and polymyositis in
      Taiwan: a nationwide population study.
AB  - BACKGROUND: Nationwide data on the epidemiology of dermatomyositis (DM) and
      polymyositis (PM) were limited. OBJECTIVES: This study was to estimate the
      incidence, occurrence of cancer and mortality of DM and PM in Taiwan. METHODS:
      Both the register of critical illness of the Taiwan National Health Insurance
      Research Dataset and the National Death Registry of Taiwan were used to calculate
      estimates of the incidence, cancer association, and mortality of DM and PM
      between 2003 and 2007. RESULTS: A total of 803 DM and 500 PM cases were
      identified between 2003 and 2007. Mean age at diagnosis was 44.0 +/- 18.3 years
      for DM and 49.2 +/- 15.9 years for PM. The overall annual incidences of DM and PM
      were 7.1 (95% CI 6.6-7.6) and 4.4 (95% CI 4.0-4.8) cases per million population.
      The incidence of both DM and PM increased with age and reached a peak at age 50
      59 years. One hundred and eleven (13.8%) patients with DM and 31 (6.2%) patients
      with PM had cancers. The diagnosis of most cancers was made after the diagnoses
      of DM (n = 71; 64.0%) and PM (n = 21; 67.7%). Overall, the standardized incidence
      ratios (SIR) for cancer were 5.36 (4.12-6.87) and 1.80 (1.10-2.79) among patients
      with DM and PM; however, during the first year, SIRs for cancer were 24.55 (95%
      CI 18.62-31.79) and 9.17 (95% CI 14.82-15.93) in patients with DM and PM,
      respectively. The most common types of cancer were nasopharyngeal cancer for men
      and breast cancer for women. Patients with DM and PM had standardized mortality
      ratios of 7.68 (6.41-9.01) and 5.29 (4.28-6.48). CONCLUSION: This study reports
      robust estimates of important aspects of the epidemiology of both DM and PM in
      Taiwan. This highlights the rarity of these diseases, and their associated cancer
      risks and increased mortality.

PMID- 21895621
TI  - Lactobacillus salivarius plus fructo-oligosaccharide is superior to fructo
      oligosaccharide alone for treating children with moderate to severe atopic
      dermatitis: a double-blind, randomized, clinical trial of efficacy and safety.
AB  - BACKGROUND: Some probiotics can ameliorate childhood atopic dermatitis (AD).
      Prebiotics have also shown some efficacy, although when combined with probiotics
      as synbiotics, their efficacy may improve. OBJECTIVE: We compared the effects of
      Lactobacillus salivarius and fructo-oligosaccharide (synbiotic) with fructo
      oligosaccharide alone (prebiotic) on children with moderate to severe AD.
      METHODS: We randomly assigned 60 children aged 2-14years with moderate to severe
      AD [SCORing AD (SCORAD)>25] to a treatment (synbiotic) or a control (prebiotic)
      group (30 per group). They received one capsule twice daily for 8weeks containing
      either L. salivarius plus fructo-oligosaccharide (treatment) or fructo
      oligosaccharide only (control). SCORAD indices were monitored at weeks 0, 4, 8
      and 10 (post-treatment). Laboratory results and AD medication use were also
      monitored. RESULTS: Baseline demographic and clinical characteristics and SCORAD
      scores were similar between the two groups. At 8weeks, the treatment group SCORAD
      scores (27.4+/-12.7) were significantly lower than for the controls (36.3+/-14.9)
      (P=0.022); this difference remained at 10weeks. At 8weeks, treatment group AD
      intensity was significantly lower (P=0.013); more children had mild AD in the
      treatment group (52%; 14/27) than the control group (30%; 8/27) (P=0.024).
      Medication use frequency and eosinophil cationic protein levels were
      significantly reduced in the treatment group at 8weeks compared with 4 weeks.
      CONCLUSION: A synbiotic combination of L. salivarius plus fructo-oligosaccharide
      is superior to the prebiotic alone for treating moderate to severe childhood AD.
      However, continued follow-up will be necessary to ascertain long-term benefits.

PMID- 21895622
TI  - Demonstration of autoantibodies against tyrosine hydroxylase in patients with
      alopecia areata.
AB  - BACKGROUND: There is strong evidence to suggest that alopecia areata (AA) is a
      tissue-specific, T cell-mediated autoimmune disease, which is usually
      characterized by patchy areas of hair loss on the scalp. Tyrosine hydroxylase
      (TH) is a known B-cell autoantigen in patients with autoimmune polyendocrine
      syndrome type 1 (APS1) associated with the presence of AA. In addition,
      melanocyte-specific proteins, gp100 and MelanA, are putative T-cell autoantigens
      in AA and so may also represent targets of the humoral immune response.
      OBJECTIVE: To analyse the sera of patients with AA for the presence of antibodies
      against TH and the melanocyte-specific proteins tyrosinase, tyrosinase-related
      protein (TRP)-1, TRP-2, gp100 and MelanA. METHODS: Radioimmunoassays were used to
      detect the relevant antibodies in sera from patients with AA (n = 32) and in sera
      from healthy individuals (n = 28). RESULTS: Of 32 patients with AA, six (19%)
      were positive for TH antibodies. A significant increase in the frequency of TH
      antibodies in the AA patient group was evident when compared with controls (P =
      0.03). Only three of 32 (9%) patients exhibited antibody responses to tyrosinase,
      TRP-1, TRP-2 and gp100. No immunoreactivity against MelanA was detected in any
      patient with AA. CONCLUSION: Antibodies against TH can be present in patients
      with AA unrelated to APS1. Humoral immune responses against tyrosinase, TRP-1,
      TRP-2, gp100 and MelanA are not prevalent in patients with AA. Overall, a
      dominant melanocyte-specific B-cell autoantigen in AA has yet to be identified.

PMID- 21895623
TI  - Ultraviolet-induced red fluorescence of patients with acne reflects regional
      casual sebum level and acne lesion distribution: qualitative and quantitative
      analyses of facial fluorescence.
AB  - BACKGROUND: The ultraviolet (UV)-induced red fluorescence of patients with acne
      has been considered to be caused by Propionibacterium acnes. OBJECTIVES: To study
      the correlation of the facial red fluorescence with the casual sebum level and
      the number of acne lesions and to investigate the difference in clinical
      features, according to both distribution and proportion of fluorescence. METHODS:
      A total of 878 patients clinically diagnosed with acne vulgaris were included.
      Inflammatory and noninflammatory acne lesions were counted separately. UV
      fluorescent photography and casual sebum level measurements were performed. UV
      induced fluorescence patterns were classified according to the facial
      distribution. The proportions of UV-induced red fluorescence were calculated.
      RESULTS: We identified six different fluorescence distribution patterns in the T
      zone (the forehead, nose and chin) and three different patterns in the U-zone
      (both cheeks). The proportion of fluorescence in the U-zone showed a positive
      correlation with the casual sebum level and the number of acne lesions. In the T
      zone, the fluorescence proportion correlated with the casual sebum level, but not
      with the number of acne lesions. As the patients' age and the age at onset
      increased, the distribution of fluorescence changed from the upper part of the T
      zone to the lower part, and to the centre of the face in the U-zone. CONCLUSIONS:
      Our results support the hypothesis that the origin of facial red fluorescence is
      sebum. In patients with acne, analyses of the pattern and proportion of UV
      induced red fluorescence can be useful for evaluating the sebum secretion and
      selecting efficient treatment modalities.

PMID- 21895624
TI  - The influence of nitric oxide synthase 2 on cutaneous wound angiogenesis.
AB  - BACKGROUND: Inducible nitric oxide synthase (nitric oxide synthase 2, NOS 2)
      inhibition significantly suppresses chronically ischaemic skin flap survival,
      possibly because of reduced angiogenesis. OBJECTIVES: To investigate the effect
      of genetic NOS 2 inhibition on cutaneous wound angiogenesis in two in vivo murine
      models. The impact of NOS 2 manipulation on vascular endothelial growth factor
      (VEGF)-A stimulated and fibroblast growth factor (FGF)-2 stimulated angiogenesis
      was also investigated in the Matrigel((r)) plug assay. METHODS: (i) Matrigel
      plugs/incisional wounds: two groups of NOS 2-/- mice and two groups of wild-type
      (WT) mice had bilateral Matrigel plugs containing 500 ng mL(-1) VEGF-A or 1000 ng
      mL(-1) FGF-2 injected subcutaneously in the abdomen. A 2.5 cm long dorsal
      incisional skin wound was created and sutured closed in the same animals. Wounds
      and plugs were explored at 7 or 12 days. (ii) Excisional wounds: dorsal 0.5 * 1.0
      cm excisional skin wounds were created in four groups (two NOS 2-/- and two WT)
      and explored at 7 or 14 days. Wounds and Matrigel plugs were examined
      histologically and morphometrically for determination of percentage vascular
      volume (PVV). RESULTS: The PVV in NOS 2-/- incisional wounds and excisional
      wounds was significantly less than in WT wounds (P = 0.05 and P < 0.001,
      respectively). The PVV was significantly less in VEGF-A stimulated Matrigel plugs
      compared with FGF-2 stimulated plugs in NOS 2-/- mice (P < 0.01), but not in WT
      mice. CONCLUSIONS: NOS 2 is significantly involved in angiogenic signalling in
      healing skin wounds, particularly within the first 7 days. However, Matrigel plug
      vascularization suggests that the role of NOS 2 in angiogenesis is related to
      VEGF-A but not FGF-2 stimulated angiogenesis.

PMID- 21895625
TI  - Misdiagnosis and delay in referral of children with localized scleroderma.
AB  - BACKGROUND: Localized scleroderma (LS) usually begins in childhood with a broad
      clinical spectrum and the diagnosis is often delayed. OBJECTIVES: To investigate
      the diagnostic pathway in a large cohort of paediatric patients with LS, to
      identify the duration until correct diagnosis and to characterize clinical clues
      for early diagnosis. METHODS: A retrospective case note review of 50 children
      with LS. RESULTS: The median (range) age at disease onset was 5.2 (0.1-14.4)
      years and disease duration until diagnosis 11.1 (1.8-79) months. The patients
      were first seen by a general practitioner (or paediatrician) after 1.2 (0.2-48.7)
      months and in none of the cases was the condition recognized at presentation
      according to a parental questionnaire (no diagnosis in 44%, misdiagnosis of
      atopic eczema 20%, melanocytic naevus 8%, fungal infection 6%, bruise 4%,
      varicose vein 4%, bacterial infection 4% and others). The patients were referred
      to a local specialist (dermatologist in 72%) after a disease duration of 7.5 (1.0
      70.9) months and in 64% the correct diagnosis was established. In 20% the
      diagnosis remained unknown, 8% were misdiagnosed as port-wine stains and others
      as atopic eczema and melanocytic naevus. The correct diagnosis was eventually
      identified by the referring dermatologists, the paediatric dermatologists at our
      hospital, external maxillofacial surgeons and a paediatrician in 29 (58%), 17
      (34%), 3 (6%) and 1 (2%), respectively. Histology was performed in 15 (30%). The
      patients were commenced on appropriate treatment after a disease duration of 16.6
      (1.8-113.4) months. The main clinical diagnostic clues were: Blaschko-linear
      distribution 76%, atrophic changes 68%, skin fibrosis 40% and loss of scalp hair
      or eyelashes 36%. CONCLUSIONS: Physicians involved in the care of these children
      need to be aware of the characteristic clinical appearance of LS for early
      recognition and prompt initiation of treatment.

PMID- 21895626
TI  - Quality of life in psoriasis and chronic hand eczema: the discrepancy in the
      definition of severity in NICE guidelines and its implications.

PMID- 21895627
TI  - Parallel use of by-passing agents in haemophilia with inhibitors: a critical
      review.
AB  - In the absence of new outbreaks of transfusion-related infections, the occurrence
      of neutralizing antibodies currently remains the most prominent complication in
      haemophilia. Coagulation factor products that may circumvent the inadequate
      activation of factor X in classical haemophilia, often referred to as bypassing
      agents, have demonstrated a high degree of efficacy. A smaller number of patients
      have been described in whom either bypassing agent, or both, demonstrate
      diminished efficacy. In those cases, the use of both bypassing agents in parallel
      was attempted, either using simultaneous (combined) or alternating (sequential)
      infusion of the two drugs, reportedly with successful haemostasis. We speculated
      whether such treatment might cause thromboembolism. A thorough literature search
      disclosed 17 reports regarding the parallel use of bypassing agents in the same
      bleeding episode in 49 patients; reporting nine patients with acquired
      haemophilia and forty patients with congenital haemophilia with inhibitors.
      Notable incidences of thromboembolic manifestations were observed: in nine
      patients with acquired haemophilia, five and in 40 patients with congenital
      haemophilia five suffered from significant thrombotic complications, and overall
      four cases were fatal. Although efficacy of parallel treatment was reported
      excellent in most cases, thromboembolism is rare in haemophilia and parallel
      treatment with activated prothrombin complex concentrate and activated
      recombinant human factor VII appears to increase the risk of thrombosis in these
      patients.

PMID- 21895628
TI  - Effects of palmitoylation of Cys(415)  in helix 8 of the CB(1)  cannabinoid
      receptor on membrane localization and signalling.
AB  - BACKGROUND AND PURPOSE: The CB(1) cannabinoid receptor is regulated by its
      association with membrane microdomains such as lipid rafts. Here, we investigated
      the role of palmitoylation of the CB(1) receptor by analysing the functional
      consequences of site-specific mutation of Cys(415) , the likely site of
      palmitoylation at the end of helix 8, in terms of membrane association, raft
      targeting and signalling. EXPERIMENTAL APPROACH: The palmitoylation state of
      CB(1) receptors in rat forebrain was assessed by
      depalmitoylation/repalmitoylation experiments. Cys(415) was replaced with alanine
      by site-directed mutagenesis. Green fluorescence protein chimeras of both wild
      type and mutant receptors were transiently expressed and functionally
      characterized in SH-SY5Y cells and HEK-293 cells by means of confocal microscopy,
      cytofluorimetry and competitive binding assays. Confocal fluorescence recovery
      after photobleaching was used to assess receptor membrane dynamics, whereas
      signalling activity was assessed by [(35) S]GTPgammaS, cAMP and co
      immunoprecipitation assays. KEY RESULTS: Endogenous CB(1) receptors in rat brain
      were palmitoylated. Mutation of Cys(415) prevented the palmitoylation of the
      receptor in transfected cells and reduced its recruitment to plasma membrane and
      lipid rafts; it also increased protein diffusional mobility. The same mutation
      markedly reduced the functional coupling of CB(1) receptors with G-proteins and
      adenylyl cyclase, whereas depalmitoylation abolished receptor association with a
      specific subset of G-proteins. CONCLUSIONS AND IMPLICATIONS: CB(1) receptors were
      post-translationally modified by palmitoylation. Mutation of Cys(415) provides a
      receptor that is functionally impaired in terms of membrane targeting and
      signalling. LINKED ARTICLES: This article is part of a themed section on
      Cannabinoids in Biology and Medicine. To view the other articles in this section
      visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of
      Cannabinoids in Biology and Medicine visit
      http://dx.doi.org/10.1111/bph.2011.163.issue-7.

PMID- 21895629
TI  - Preclinical development of CAT-354, an IL-13 neutralizing antibody, for the
      treatment of severe uncontrolled asthma.
AB  - BACKGROUND AND PURPOSE: IL-13 is a pleiotropic Th2 cytokine considered likely to
      play a pivotal role in asthma. Here we describe the preclinical in vitro and in
      vivo characterization of CAT-354, an IL-13-neutralizing IgG4 monoclonal antibody
      (mAb), currently in clinical development. EXPERIMENTAL APPROACH: In vitro the
      potency, specificity and species selectivity of CAT-354 was assayed in TF-1
      cells, human umbilical vein endothelial cells and HDLM-2 cells. The ability of
      CAT-354 to modulate disease-relevant mechanisms was tested in human cells
      measuring bronchial smooth muscle calcium flux induced by histamine, eotaxin
      generation by normal lung fibroblasts, CD23 upregulation in peripheral blood
      mononuclear cells and IgE production by B cells. In vivo CAT-354 was tested on
      human IL-13-induced air pouch inflammation in mice, ovalbumin-sensitization and
      challenge in IL-13 humanized mice and antigen challenge in cynomolgus monkeys.
      KEY RESULTS: CAT-354 has a 165 pM affinity for human IL-13 and functionally
      neutralized human, human variant associated with asthma and atopy (R130Q) and
      cynomolgus monkey, but not mouse, IL-13. CAT-354 did not neutralize human IL-4.
      In vitro CAT-354 functionally inhibited IL-13-induced eotaxin production, an
      analogue of smooth muscle airways hyperresponsiveness, CD23 upregulation and IgE
      production. In vivo in humanized mouse and cynomolgus monkey antigen challenge
      models CAT-354 inhibited airways hyperresponsiveness and bronchoalveolar lavage
      eosinophilia. CONCLUSIONS AND IMPLICATIONS: CAT-354 is a potent and selective IL
      13-neutralizing IgG4 mAb. The preclinical data presented here support the
      trialling of this mAb in patients with moderate to severe uncontrolled asthma.

PMID- 21895630
TI  - Small molecule chemokine mimetics suggest a molecular basis for the observation
      that CXCL10 and CXCL11 are allosteric ligands of CXCR3.
AB  - BACKGROUND AND PURPOSE: The chemokine receptor CXCR3 directs migration of T-cells
      in response to the ligands CXCL9/Mig, CXCL10/IP-10 and CXCL11/I-TAC. Both ligands
      and receptors are implicated in the pathogenesis of inflammatory disorders,
      including atherosclerosis and rheumatoid arthritis. Here, we describe the
      molecular mechanism by which two synthetic small molecule agonists activate
      CXCR3. EXPERIMENTAL APPROACH: As both small molecules are basic, we hypothesized
      that they formed electrostatic interactions with acidic residues within CXCR3.
      Nine point mutants of CXCR3 were generated in which an acidic residue was mutated
      to its amide counterpart. Following transient expression, the ability of the
      constructs to bind and signal in response to natural and synthetic ligands was
      examined. KEY RESULTS: The CXCR3 mutants D112N, D195N and E196Q were efficiently
      expressed and responsive in chemotaxis assays to CXCL11 but not to CXCL10 or to
      either of the synthetic agonists, confirmed with radioligand binding assays.
      Molecular modelling of both CXCL10 and CXCR3 suggests that the small molecule
      agonists mimic a region of the '30s loop' (residues 30-40 of CXCL10) which
      interacts with the intrahelical CXCR3 residue D112, leading to receptor
      activation. D195 and E196 are located in the second extracellular loop and form
      putative intramolecular salt bridges required for a CXCR3 conformation that
      recognizes CXCL10. In contrast, CXCL11 recognition by CXCR3 is largely
      independent of these residues. CONCLUSION AND IMPLICATIONS: We provide here a
      molecular basis for the observation that CXCL10 and CXCL11 are allosteric ligands
      of CXCR3. Such findings may have implications for the design of CXCR3
      antagonists.

PMID- 21895632
TI  - Functional selectivity of central Galpha-subunit proteins in mediating the
      cardiovascular and renal excretory responses evoked by central alpha(2) 
      adrenoceptor activation in vivo.
AB  - BACKGROUND AND PURPOSE: Activation of brain alpha(2) -adrenoceptors in conscious
      rodents decreases heart rate (HR) and mean arterial blood pressure (MAP) and
      increases urine output and urinary sodium excretion. In vitro, alpha(2) 
      adrenoceptor stimulation activates Galpha(i(1-3)) , Galpha(o) and Galpha(s) 
      subunit protein-gated signal transduction pathways. Here we have investigated
      whether these same Galpha-subunit protein-gated pathways mediate the
      cardiovascular and renal excretory responses to central alpha(2) -adrenoceptor
      activation in conscious Sprague-Dawley rats. EXPERIMENTAL APPROACH: Rats were pre
      treated by intracerebroventricular injection (i.c.v.) with an
      oligodeoxynucleotide (ODN) targeted to a Galpha(i1) , Galpha(i2) , Galpha(i3) ,
      Galpha(o) , Galpha(s) or a scrambled (SCR) ODN sequence (25 ug, 24 h). On the day
      of study, the alpha(2) -adrenoceptor agonist guanabenz (50 ug) or saline vehicle,
      was injected i.c.v. into ODN-pre-treated conscious rats. MAP and HR were
      recorded, and urine was collected for 150 min. KEY RESULTS: In vehicle- and SCR
      ODN-pre-treated rats, i.c.v. guanabenz decreased MAP and HR, and produced marked
      diuretic and natriuretic responses. Selective ODN-mediated down-regulation of
      brain Galpha(i2) -subunit proteins abolished the central guanabenz-induced
      hypotension and natriuresis. In contrast, following selective Galpha(s) down
      regulation, the characteristic hypotensive response to i.c.v. guanabenz was
      converted to an immediate increase in MAP. The bradycardic and diuretic responses
      to i.c.v. guanabenz were not blocked by pre-treatment with any ODN. CONCLUSIONS
      AND IMPLICATIONS: There was functional selectivity of Galpha(i2) and Galpha(s)
      subunit protein-gated signal transduction pathways in mediating the hypotensive
      and natriuretic, but not bradycardic or diuretic, responses evoked by central
      alpha(2) -adrenoceptor activation in vivo.

PMID- 21895633
TI  - Audiological findings in 100 USH2 patients.
AB  - Bilateral sensorineural hearing loss (HL), classically described as mild to
      severe with a typically down-sloping audiometric configuration, is the earliest
      symptom occurring in Usher syndrome type II (USH2). Audiological findings were
      analyzed in a total of 100 USH2 patients (92 families) divided into three groups
      according to the gene involved: 88 USH2A, 10 GPR98 and 2 DFNB31 patients. A fine
      analysis of audiograms was performed (pure tone average, degree of severity,
      configuration). The median age of HL diagnosis was 5 years (range 8 months-31
      years) although the median age at USH2 diagnosis was 34.5 (range 8-76). Moderate
      HL was predominant (76%) and a gently down-sloping configuration characterized
      most audiograms (66%). No statistically significant difference was found between
      USH2A and GPR98 patients but a tendency was clearly noted for more GPR98 patients
      to present with severe hearing loss. It is not possible to predict the mutated
      gene from audiograms.

PMID- 21895631
TI  - Human obesity and endothelium-dependent responsiveness.
AB  - Obesity is an ongoing worldwide epidemic. Besides being a medical condition in
      itself, obesity dramatically increases the risk of development of metabolic and
      cardiovascular disease. This risk appears to stem from multiple abnormalities in
      adipose tissue function leading to a chronic inflammatory state and to
      dysregulation of the endocrine and paracrine actions of adipocyte-derived
      factors. These, in turn, disrupt vascular homeostasis by causing an imbalance
      between the NO pathway and the endothelin 1 system, with impaired insulin
      stimulated endothelium-dependent vasodilation. Importantly, emerging evidence
      suggests that the vascular dysfunction of obesity is not just limited to the
      endothelium, but also involves the other layers of the vessel wall. In
      particular, obesity-related changes in medial smooth muscle cells seem to disrupt
      the physiological facilitatory action of insulin on the responsiveness to
      vasodilator stimuli, whereas the adventitia and perivascular fat appear to be a
      source of pro-inflammatory and vasoactive factors that may contribute to
      endothelial and smooth muscle cell dysfunction, and to the pathogenesis of
      vascular disease. While obesity-induced vascular dysfunction appears to be
      reversible, at least in part, with weight control strategies, these have not
      proved sufficient to prevent the metabolic and cardiovascular complication of
      obesity on a large scale. While a number of currently available drugs have shown
      potentially beneficial vascular effects in patients with obesity and the
      metabolic syndrome, elucidation of the pathophysiological mechanisms underlying
      vascular damage in obese patients is necessary to identify additional
      pharmacologic targets to prevent the cardiovascular complications of obesity, and
      their human and economic costs. LINKED ARTICLES: This article is part of a themed
      section on Fat and Vascular Responsiveness. To view the other articles in this
      section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3.

PMID- 21895634
TI  - Recent genomic advances in schizophrenia.
AB  - Recent studies have supported the hypothesis based upon expectations from
      population genetics that the high heritability of schizophrenia reflects a
      combination of relatively common alleles of small effect and rare alleles some
      with relatively large effects. Genome-wide association studies have identified a
      number of risk loci at genome-wide levels of significance as well as evidence for
      a substantial burden of common risk loci. Moreover these recent findings suggest
      genetic overlap with bipolar disorder which has traditionally been assumed to be
      genetically distinct from schizophrenia. Genome-wide studies of at least one
      class of relatively uncommon variant, submicroscopic chromosomal abnormalities
      often referred to as copy number variations (CNVs), suggest that these confer
      high risk of schizophrenia. There is evidence both for an increased burden of
      large, rare CNVs in schizophrenia and that risk is conferred by a number of
      specific large CNVs as well as by deletions of NRXN1 which encodes the synaptic
      scaffolding protein neurexin 1. Many of these CNVs have been implicated in
      autism, mental retardation, epilepsy and other neurodevelopment disorders. These
      findings have implications for pathogenesis and nosology of schizophrenia and
      related disorders, and for future genetic studies.

PMID- 21895635
TI  - BRCA1 and BRCA2 mutations among familial breast cancer patients from Costa Rica.
AB  - The contribution of mutations in BRCA1 and BRCA2 genes to the burden of breast
      cancer in Costa Rica has not been studied. We estimated the frequency of BRCA
      mutations among 111 Costa Rican women with breast cancer and a family history of
      breast cancer. These women were mainly from the metropolitan area of San Jose. A
      detailed family history was obtained from each patient and a blood sample was
      processed for DNA extraction. Mutations in BRCA1 and BRCA2 were sought using a
      combination of techniques and all mutations were confirmed by direct sequencing.
      Four different mutations were identified in five patients (four in BRCA2 and one
      in BRCA1) representing 4.5% of the total. Two unrelated patients were found to
      have a BRCA2 5531delTT mutation. Other BRCA2 mutations included C5507G and
      6174delT. Only one BRCA1 mutation was found (C3522T). The family with the BRCA1
      mutation had five cases of gastric cancer. Families with BRCA2 mutations were
      also reported to have cases of gastric and prostate cancers; however, the full
      range of cancers associated with BRCA1 and BRCA2 mutations in Costa Rica has not
      yet been established.

PMID- 21895636
TI  - Detection of chromosomal aneuploidies in fetal cells isolated from maternal blood
      using single-chromosome dual-probe FISH analysis.
AB  - Detection of chromosomal aneuploidies using fetal cells isolated from maternal
      blood, for prenatal non-invasive genetic investigation, has been a long-sought
      goal of clinical genetics to replace amniocentesis and chorionic villous sampling
      to avoid any risk to the fetus. The purpose of this study was to develop a
      sensitive and specific new assay for diagnosing aneuploidy with circulating fetal
      cells isolated from maternal blood as previously reported using two novel
      approaches: (i) simultaneous immunocytochemistry (ICC) evaluation using a
      monoclonal antibody for i-antigen, followed by fluorescence in situ hybridization
      (FISH); (ii) dual-probe FISH analysis of interphase nuclei using two differently
      labeled probes, specific for different loci of chromosomes 21 and 18; in
      addition, short tandem repeats (STR) analysis on single cells isolated by
      micromanipulation was applied to confirm the presence of fetal cells in the cell
      sample enriched from maternal blood. Blood samples were obtained from women
      carrying trisomic fetuses, and from non-pregnant women and men as controls. Using
      ICC-FISH approach, a large heterogeneity in immunostaining pattern was observed,
      which is a source of very subjective signal interpretation. Differently, dual
      probe FISH analysis provided for a correct diagnosis of all pregnancies: the mean
      percentage of trisomic cells was 0.5% (range, 0.36-0.76%), while the mean
      percentage of trisomic cells in the control group (normal pregnancies or non
      pregnant women) was <=0.20%. The application of the dual-probe FISH protocol on
      fetal cells isolated from maternal blood enables accurate molecular detection of
      fetal aneuploidy, thus providing a foundation for development of non-invasive
      prenatal diagnostic testing.

PMID- 21895637
TI  - Isolated and syndromic forms of congenital anosmia.
AB  - Loss of smell (anosmia) is common in the general population and the frequency
      increases with age. A much smaller group have no memory of ever being able to
      smell and are classified as having isolated congenital anosmia (ICA). Families
      are rare, and tend to present in a dominant inheritance pattern. Despite a strong
      degree of heritability, no human disease-causing mutations have been identified.
      Anosmia is part of the clinical spectrum in various diseases, as seen in Kallmann
      syndrome, various ciliopathies and congenital insensitivity to pain. This review
      will focus on ICA through already published families and cases as well as
      syndromes where anosmia is part of the clinical disease spectrum. Furthermore,
      olfactory signal transduction pathway genes and animal models may shed light on
      potential candidate genes and pathways involved in ICA.

PMID- 21895639
TI  - Of ORC and forks: the identification of mutations implicated in Meier-Gorlin
      syndrome.

PMID- 21895638
TI  - Adverse childhood experiences of persons at risk for Huntington's disease or
      BRCA1/2 hereditary breast/ovarian cancer.
AB  - Huntington's disease (HD) is known to have a negative impact on family life.
      Offspring of HD patients may be exposed to adversity in childhood because of the
      parent's disease and its psychological consequences. BRCA1/2 hereditary breast
      and ovarian cancer (BRCA1/2) increases the risk for offspring of being exposed to
      parental disease or loss. Childhood adversity is associated with psychopathology
      and various other problems in later life. Adverse childhood experiences (ACEs)
      before age 16 were assessed in adults at 50% risk for HD (n = 74) or BRCA1/2 (n =
      82) and in controls (n = 101), using the Negative Life Events Scale. Mean number
      and occurrence of ACEs were compared between groups. The odds of having
      experienced adversity in childhood were higher in HD offspring and BRCA1/2
      offspring than in controls. HD offspring reported a higher mean number of ACEs
      than controls or BRCA1/2 offspring. In HD offspring, the prevalence of parental
      disease and parental dysfunction experienced before age 16 was higher than in
      controls. In BRCA1/2 offspring, the prevalence of parental loss before age 16 was
      higher than in controls. This study indicates that 53% of HD offspring and 45% of
      BRCA1/2 offspring are exposed to adversity in childhood or adolescence. The
      relevance of these findings for counseling in predictive testing programs,
      reproductive decision-making, and child rearing matters is discussed.

PMID- 21895640
TI  - Polycystin-1: a key player in hereditary cystic kidney and liver disorders.

PMID- 21895641
TI  - Systematic screening of FBN1 gene unclassified missense variants for splice
      abnormalities.
AB  - Defects at the level of pre-mRNA splicing are a common source of genetic mutation
      but such mutations are not always easy to identify from DNA sequence data alone.
      Clinical practice has only recently begun to incorporate analysis for this type
      of abnormality. Some base changes at the DNA level currently viewed as
      unclassified variants or missense mutations may influence RNA splicing. To
      address this problem for fibrillin 1 (FBN1) gene missense mutations we have
      carried out RNA analysis and in silico analysis with splice site prediction
      programs on 40 cases with 36 different mutations. Direct analysis of RNA from
      blood was performed by cDNA preparation, PCR amplification of specific FBN1
      fragments, gel electrophoresis and sequencing of the PCR products. Of the 36
      missense base changes, direct RNA analysis identified 2 which caused an
      abnormality of splicing. In silico analysis using five splice site prediction
      programs did not always accurately predict the splicing seen by direct RNA
      analysis. In conclusion, some apparent missense mutations have an effect on
      splicing which can be identified by direct RNA analysis, however, in silico
      analysis of splice sites is not always accurate, should be carried out with more
      than one prediction program and results should be used with caution.

PMID- 21895642
TI  - A population-based study and systematic review of hearing loss in children with
      cerebral palsy.
AB  - AIM: The aims of this study were to estimate the frequency of hearing loss in
      children with cerebral palsy (CP), to examine factors associated with hearing
      loss, and to describe aspects of hearing in a population sample of children with
      CP and hearing loss. METHOD: A systematic review of the international literature
      was undertaken, and data on the frequency of hearing loss or severe hearing loss
      were extracted from 14 data sets based on previously devised criteria. Six
      hundred and eight-five children with CP (406 males, 279 females) born in
      Victoria, Australia, between 1999 and 2004 were identified from the Victorian
      Cerebral Palsy Register. Children were included if they had an established post
      neonatal cause for their CP before the age of 2 years. Additional information was
      collected on 48 children with documented hearing loss based on a four-tone pure
      tone average in the better ear. RESULTS: There was considerable variation in the
      definitions and proportions of hearing loss (range 4-13%) and severe hearing loss
      (range 2-12%) reported by CP registries in developed countries. In Victoria, 7%
      of individuals with CP had bilateral hearing loss of a moderate to profound
      degree, whereas the subgroup with a severe-profound degree of loss constituted 3%
      to 4% of the CP population. INTERPRETATION: These population-based data are
      likely to more accurately reflect the true frequency of defined hearing loss in
      children with CP than previous reviews.

PMID- 21895643
TI  - Describing hearing in individuals with cerebral palsy.

PMID- 21895644
TI  - Unilateral periventricular leukomalacia in association with pyruvate
      dehydrogenase deficiency.
AB  - Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic
      acidosis and neurological dysfunction in infancy and early childhood. A
      deficiency of PDH E1 alpha, a subunit of the PDH complex, is a prominent cause of
      congenital lactic acidosis. We describe a female infant born at term and
      delivered by emergency Caesarean section because of fetal distress. There was no
      parental consanguinity. She presented at 5 months of age with failure to thrive,
      microcephaly, hypertonia, and developmental impairment. Her plasma and
      cerebrospinal fluid lactate were raised. She had raised plasma pyruvate with a
      normal lactate-pyruvate ratio. Magnetic resonance imaging of the brain showed a
      focal dilatation of the right lateral ventricle with unilateral periventricular
      leukomalacia (PVL) with subependymal cyst. Skin fibroblast culture assay revealed
      PDH deficiency, confirmed by mutation analysis of the E1 alpha subunit. At 18
      months of age, she has hypertonia and global impairment and is making slow
      progress. Denver II assessment showed delay in gross motor, fine motor, adaptive,
      personal, social, and language categories. She has been treated with
      dichloroacetate and a ketogenic diet since the age of 10 and 13 months
      respectively, without any side effects. To our knowledge, unilateral PVL as a
      neuroradiological feature has not been described in children with PDH deficiency.
      PDH deficiency should be considered as a differential diagnosis if PVL is
      unilateral and if the perinatal history is not typical of PVL.

PMID- 21895645
TI  - Spring water and water culture on Jeju island.

PMID- 21895646
TI  - NAPL source zone depletion model and its application to railroad-tank-car spills.
AB  - We developed a new semi-analytical source zone depletion model (SZDM) for
      multicomponent light nonaqueous phase liquids (LNAPLs) and incorporated this into
      an existing screening model for estimating cleanup times for chemical spills from
      railroad tank cars that previously considered only single-component LNAPLs.
      Results from the SZDM compare favorably to those from a three-dimensional
      numerical model, and from another semi-analytical model that does not consider
      source zone depletion. The model was used to evaluate groundwater contamination
      and cleanup times for four complex mixtures of concern in the railroad industry.
      Among the petroleum hydrocarbon mixtures considered, the cleanup time of diesel
      fuel was much longer than E95, gasoline, and crude oil. This is mainly due to the
      high fraction of low solubility components in diesel fuel. The results
      demonstrate that the updated screening model with the newly developed SZDM is
      computationally efficient, and provides valuable comparisons of cleanup times
      that can be used in assessing the health and financial risk associated with
      chemical mixture spills from railroad-tank-car accidents.

PMID- 21895647
TI  - Field test of the superconducting gravimeter as a hydrologic sensor.
AB  - We report on a field test of a transportable version of a superconducting
      gravimeter (SG) intended for groundwater storage monitoring. The test was
      conducted over a 6-month period at a site adjacent to a well in the recharge zone
      of the karstic Edwards Aquifer, a major groundwater resource in central Texas.
      The purpose of the study was to assess requirements for unattended operation of
      the SG in a field setting and to obtain a gravimetric estimate of aquifer
      specific yield. The experiment confirmed successful operation of the SG, but
      water level changes were small (<0.3 m) leading to uncertainty in the estimate of
      specific yield. Barometric pressure changes were the dominant cause of both water
      level variations and non-tidal gravity changes. The specific yield estimate
      (0.26) is larger than most published values and dependent mainly on low frequency
      variations in residual gravity and water level time series.

PMID- 21895648
TI  - Phylogenetic structure illuminates the mechanistic role of environmental
      heterogeneity in community organization.
AB  - 1. Diversity begets diversity. Numerous published positive correlations between
      environmental heterogeneity and species diversity indicate ubiquity of this
      phenomenon. Nonetheless, most assessments of this relationship are
      phenomenological and provide little insight into the mechanism whereby such
      positive association results. 2. Two unresolved issues could better illuminate
      the mechanistic basis to diversity begets diversity. First, as environmental
      heterogeneity increases, both productivity and the species richness that
      contributes to that productivity often increase in a correlated fashion thus
      obscuring the primary driver. Second, it is unclear how species are added to
      communities as diversity increases and whether additions are trait based. 3. We
      examined these issues based on 31 rodent communities in the central Mojave
      Desert. At each site, we estimated rodent species richness and characterized
      environmental heterogeneity from the perspectives of standing primary
      productivity and number of seed resources. We further examined the phylogenetic
      structure of communities by estimating the mean phylogenetic distance (MPD) among
      species and by comparing empirical phylogenetic distances to those based on
      random assembly from a regional species pool. 4. The relationship between rodent
      species diversity and environmental heterogeneity was positive and significant.
      Moreover, diversity of resources accounted for more unique variation than did
      total productivity, suggesting that variety and not total amount of resource was
      the driver of increased rodent diversity. Relationships between environmental
      heterogeneity and phylogenetic distance were negative and significant; species
      were significantly phylogenetically over-dispersed in communities of low
      environmental heterogeneity and became more clumped as environmental
      heterogeneity increased. 5. Results suggest that species diversity increases with
      environmental heterogeneity because a wider variety of resources allow greater
      species packing within communities.

PMID- 21895649
TI  - Adolescents' self-reported suicide attempts, self-harm thoughts and their
      correlates across 17 European countries.
AB  - BACKGROUND:   Suicide is a leading cause of death among adolescents in Europe.
      Self-harm thoughts and behaviours are documented precursors of completed suicide.
      It is therefore of great importance to investigate the prevalence of suicide
      thoughts and attempts and their correlates, with the aim of preventing this major
      life-threatening public health problem. This study provides cross-national
      European data on self-reported suicidal thoughts and attempts among adolescents.
      METHODS:   Data were obtained from 45,806 high school students aged 15-16 years
      from 17 countries that participated in the European School Survey Project on
      Alcohol and Other Drugs (ESPAD) 2007 school survey. The standardised methods of
      the ESPAD survey ensure comparability across countries. Students completed an
      anonymous questionnaire in their classrooms. The prevalences of suicidal thoughts
      and attempts are reported as well as their sociodemographic and psychosocial
      correlates identified in logistic regression. RESULTS:   The median prevalence of
      any lifetime self-reported suicide attempt was 10.5% across the participating
      countries (range 4.1%-23.5%). The median of frequent self-harm thoughts (at least
      five times) was 7.4% (range 2.1%-15.3%). Suicidal behaviour and thoughts had
      significant associations with gender, substance use, family integrity and
      socioeconomic status. Countries with higher prevalence of substance use tended to
      have a weaker association between substance use and self-reported suicide
      attempts. CONCLUSION:   Although self-reported self-harm thoughts and suicide
      attempts vary in prevalence within Europe, there are common correlates across
      countries. These have an important impact on understanding the phenomenon of
      suicide among young people and in guiding prevention.

PMID- 21895650
TI  - Electrocortical reactivity to emotional faces in young children and associations
      with maternal and paternal depression.
AB  - BACKGROUND: The late positive potential (LPP) is an event-related potential
      component that indexes selective attention toward motivationally salient
      information and is sensitive to emotional stimuli. Few studies have examined the
      LPP in children. Depression has been associated with reduced reactivity to
      negative and positive emotional stimuli, including reduced LPPs in response to
      emotional faces. The current study sought to identify the time course and scalp
      distribution of the LPP in response to emotional faces in young children and to
      determine whether reduced reactivity is observed among children at risk for
      depression. METHODS: Electrocortical reactivity to emotional faces was examined
      in a large sample of young children and as a function of maternal and paternal
      depression. RESULTS: In the overall sample, emotional faces were associated with
      increased positivities compared to neutral faces at occipital sites 200-600 ms
      after stimulus onset and at parietal sites 600-1,000 ms after stimulus onset.
      Children of mothers with a history of depressive disorders exhibited reduced
      differentiation in the early occipital LPP for emotional compared to neutral
      faces. CONCLUSIONS: Results suggest that children as young as 6 years exhibit
      LPPs to emotional faces, and patterns of electrocortical reactivity to emotional
      stimuli may be associated with vulnerability to depressive disorders.

PMID- 21895651
TI  - Annual research review: hoarding disorder: potential benefits and pitfalls of a
      new mental disorder.
AB  - BACKGROUND: The inclusion of a new mental disorder in the nomenclature is not a
      trivial matter. Many have highlighted the risks of an ever-increasing number of
      mental disorders and of overpathologizing human behaviour. Given the proposed
      inclusion of a new hoarding disorder (HD) in DSM-5 (Diagnostic and Statistical
      Manual of Mental Disorders, fifth edition), it is pertinent to discuss the
      potential benefits and pitfalls of such a development. METHOD: In this article,
      we examine whether HD fits with the current DSM-IV (Diagnostic and Statistical
      Manual of Mental Disorders, fourth edition) and proposed DSM-5 definitions of
      'mental disorder'. We next discuss the potential benefits and risks of the
      creation of this diagnosis. Finally, we address some additional considerations
      that may arise when proposing a new disorder for the nomenclature and identify
      some of the gaps in the knowledge base. CONCLUSION:   HD fits the current DSM-IV
      and proposed DSM-5 definitions for a mental disorder. On balance, the potential
      benefits of creating the new diagnosis (e.g. identification of the majority of
      cases who clearly suffer and need help but are currently missed out by the
      existing diagnostic categories) outweigh the potential harms (e.g. pathologizing
      normal behaviour). Whether the criteria will need modification for their use in
      children/adolescents is unclear and more research is needed to address this
      question.

PMID- 21895652
TI  - Figure of merit for environmental SEM and its implications.
AB  - A recently introduced figure of merit for environmental and low vacuum scanning
      electron microscopes has now been computed in the full operational pressure range
      for one commercial instrument. The direct simulation Monte Carlo method has been
      used in lieu of experimental measurements. The theory of this figure of merit is
      further consolidated. It is shown that a thin pressure limiting aperture can
      indeed be used as an optimum reference system for all instruments employing
      differential pumping in the transfer of an electron beam from high vacuum to high
      pressure. The implications of the results obtained are discussed both in relation
      to existing commercial instruments and associated literature to pave the way for
      future progress in the field.

PMID- 21895653
TI  - Automated and semi-automated cell tracking: addressing portability challenges.
AB  - Cell tracking is a key task in the high-throughput quantitative study of
      important biological processes, such as immune system regulation and
      neurogenesis. Variability in cell density and dynamics in different videos,
      hampers portability of existing trackers across videos. We address these
      potability challenges in order to develop a portable cell tracking algorithm. Our
      algorithm can handle noise in cell segmentation as well as divisions and deaths
      of cells. We also propose a parameter-free variation of our tracker. In the
      tracker, we employ a novel method for recovering the distribution of cell
      displacements. Further, we present a mathematically justified procedure for
      determining the gating distance in relation to tracking performance. For the
      range of real videos tested, our tracker correctly recovers on average 96% of
      cell moves, and outperforms an advanced probabilistic tracker when the cell
      detection quality is high. The scalability of our tracker was tested on synthetic
      videos with up to 200 cells per frame. For more challenging tracking conditions,
      we propose a novel semi-automated framework that can increase the ratio of
      correctly recovered tracks by 12%, through selective manual inspection of only
      10% of all frames in a video.

PMID- 21895654
TI  - Determination of spatial correlation functions of refractive index of living
      tissue.
AB  - We present what to our knowledge the first method of determination of spatial
      correlation functions of refractive index fluctuations of living tissues by
      Fourier domain optical coherence tomography (FDOCT). Based on the second-order
      statistical description of the random characteristic of living tissue, a formula
      which clearly relates the spectral electrical power from the detector to the
      Fourier spectrum of the refractive index correlation function is given. The
      method is characterized by its capability of noninvasive measurements in vivo. It
      has the potential of allowing quantitative discrimination between different
      tissue types or the same tissue at different pathological states by determining
      their Fourier components of spatial correlation functions of refractive index.

PMID- 21895655
TI  - Mouse class III myosins: kinase activity and phosphorylation sites.
AB  - As class III unconventional myosins are motor proteins with an N-terminal kinase
      domain, it seems likely they play a role in both signaling and actin based
      transport. A growing body of evidence indicates that the motor functions of human
      class IIIA myosin, which has been implicated in progressive hearing loss, are
      modulated by intermolecular autophosphorylation. However, the phosphorylation
      sites have not been identified. We studied the kinase activity and
      phosphorylation sites of mouse class III myosins, mMyo3A and 3B, which are highly
      similar to their human orthologs. We demonstrate that the kinase domains of
      mMyo3A and 3B are active kinases, and that they have similar, if not identical,
      substrate specificities. We show that the kinase domains of these proteins
      autophosphorylate, and that they can phosphorylate sites within their myosin and
      tail domains. Using liquid chromatography-mass spectrometry, we identified
      phosphorylated sites in the kinase, myosin motor and tail domains of both mMyo3A
      and 3B. Most of the phosphorylated sites we identified and their consensus
      phosphorylation motifs are highly conserved among vertebrate class III myosins,
      including human class III myosins. Our findings are a major step toward
      understanding how the functions of class III myosins are regulated by
      phosphorylation.

PMID- 21895656
TI  - The immune molecule CD3zeta and its downstream effectors ZAP-70/Syk mediate
      ephrin signaling in neurons to regulate early neuritogenesis.
AB  - Recent studies have highlighted the key role of the immune protein CD3zeta in the
      maturation of neuronal circuits in the CNS. Yet, the upstream signals that might
      recruit and activate CD3zeta in neurons are still unknown. In this study, we show
      that CD3zeta functions early in neuronal development and we identify ephrinA1
      dependent EphA4 receptor activation as an upstream regulator of CD3zeta. When
      newly born neurons are still spherical, before neurite extension, we found a
      transient CD3zeta aggregation at the cell periphery matching the initiation site
      of the future neurite. This accumulation of CD3zeta correlated with a stimulatory
      effect on filopodia extension via a Rho-GEF Vav2 pathway and a repression of
      neurite outgrowth. Conversely, cultured neurons lacking CD3zeta isolated from
      CD3zeta(-/-) mice showed a decreased number of filopodia and an enhanced neurite
      number. Stimulation with ephrinA1 induces the translocation of both CD3zeta and
      its activated effector molecules, ZAP-70/Syk tyrosine kinases, to EphA4 receptor
      clusters. EphrinA1-induced growth cone collapse was abrogated in CD3zeta(-/-)
      neurons and was markedly reduced by ZAP-70/Syk inhibition. Moreover, ephrinA1
      induced ZAP-70/Syk activation was inhibited in CD3zeta(-/-) neurons. Altogether,
      our data suggest that CD3zeta mediates the ZAP-70/Syk kinase activation triggered
      by ephrinA-activated pathway to regulate early neuronal morphogenesis.

PMID- 21895657
TI  - Smad proteins differentially regulate transforming growth factor-beta-mediated
      induction of chondroitin sulfate proteoglycans.
AB  - Traumatic injury to the CNS results in increased expression and deposition of
      chondroitin sulfate proteoglycans (CSPGs) that are inhibitory to axonal
      regeneration. Transforming growth factor-beta (TGF-beta) has been implicated as a
      major mediator of these changes, but the mechanisms through which TGF-beta
      regulates CSPG expression are not known. Using lentiviral expressed Smad-specific
      ShRNA we show that TGF-beta induction of CSPG expression in astrocytes is Smad
      dependent. However, we find a differential dependence of the synthetic machinery
      on Smad2 and/or Smad3. TGF-beta induction of neurocan and xylosyl transferase 1
      required both Smad2 and Smad3, whereas induction of phosphacan and chondroitin
      synthase 1 required Smad2 but not Smad3. Smad3 knockdown selectively reduced
      induction of chondroitin-4-sulfotransferase 1 and the amount of 4-sulfated CSPGs
      secreted by astrocytes. Additionally, Smad3 knockdown in astrocytes was more
      efficacious in promoting neurite outgrowth of neurons cultured on the TGF-beta
      treated astrocytes. Our data implicate TGF-beta Smad3-mediated induction of 4
      sulfation as a critical determinant of the permissiveness of astrocyte secreted
      CSPGs for axonal growth.

PMID- 21895659
TI  - beta-Lactotensin derived from bovine beta-lactoglobulin exhibits anxiolytic-like
      activity as an agonist for neurotensin NTS(2)  receptor via activation of
      dopamine D(1)  receptor in mice.
AB  - beta-Lactotensin (His-Ile-Arg-Leu) is a bioactive peptide derived from bovine
      milk beta-lactoglobulin, acting as a natural agonist for neurotensin receptors.
      We found that beta-lactotensin exhibited anxiolytic-like activity in an elevated
      plus-maze test after its intraperitoneal (i.p.) administration in mice. beta
      Lactotensin was also orally active. The anxiolytic-like activity of beta
      lactotensin after i.p. administration was blocked by levocabastine, an antagonist
      for the neurotensin NTS(2) receptor. beta-Lactotensin had anxiolytic-like
      activity in wild-type but not Ntsr2-knockout mice. beta-Lactotensin increased
      intracellular Ca(2+) flux in glial cells derived from wild-type mice but not
      Ntsr2 knockout mice. These results suggest that beta-lactotensin acts as an
      NTS(2) receptor agonist having anxiolytic-like activity. The anxiolytic-like
      activity of beta-lactotensin was also blocked by SCH23390 and SKF83566,
      antagonists for dopamine D(1) receptor, but not by raclopride, an antagonist for
      D(2) receptor. Taken together, beta-lactotensin may exhibit anxiolytic-like
      activity via NTS(2) receptor followed by D(1) receptor.

PMID- 21895660
TI  - Irsogladine maleate regulates epithelial barrier function in tumor necrosis
      factor-alpha-stimulated human gingival epithelial cells.
AB  - BACKGROUND AND OBJECTIVE: As epithelial cells function as a mechanical barrier,
      the permeability of the gingival epithelial cell layer indicates a defensive
      capability against invasion by periodontal pathogens. We have reported the
      expression of claudin-1 and E-cadherin, key regulators of permeability, in the
      gingival junctional epithelium. Irsogladine maleate (IM) is a medication for
      gastric ulcers and also regulates Aggregatibacter actinomycetemcomitans-stimuated
      chemokine secretion and E-cadherin expression in gingival epithelium. In this
      study, we have further investigated the effects of IM on the barrier functions of
      gingival epithelial cells under inflammatory conditions. MATERIAL AND METHODS: We
      examined the permeability, and the expression of claudin-1 and E-cadherin, in
      human gingival epithelial cells (HGECs) stimulated with tumor necrosis factor
      (TNF)-alpha, with or without IM. RESULTS: TNF-alpha increased the permeability of
      HGECs, and IM abolished the increase. TNF-alpha reduced the expression of E
      cadherin in HGECs, and IM reversed the reduction. In addition, immunofluorescence
      staining showed that TNF-alpha disrupted claudin-1 expression in HGECs, and IM
      reversed this effect. CONCLUSION: The results suggest that IM reverses the TNF
      alpha-induced disruption of the gingival epithelial barrier by regulating E
      cadherin and claudin-1.

PMID- 21895661
TI  - Hepatocytes produce tumor necrosis factor-alpha and interleukin-6 in response to
      Porphyromonas gingivalis.
AB  - BACKGROUND AND OBJECTIVE: The liver plays a major role in clearing systemic
      bacterial infections. In addition, inflammatory cytokines produced in the liver
      play a critical role in systemic cytokine levels. The aim of this study was to
      investigate the production of tumor necrosis factor-alpha (TNF-alpha) and
      interleukin-6 (IL-6) by hepatocytes in response to periodontal pathogens.
      MATERIAL AND METHODS: The mouse hepatic carcinoma cell line Hepa-1.6 and the
      mouse macrophage-like cell line RAW 264 were co-cultured in Transwell insert
      plates. Cells were stimulated with bacterial extracts prepared from Porphyromonas
      gingivalis and the induction of TNF-alpha and IL-6 was measured using real-time
      PCR and ELISA. RESULTS: After stimulation with bacteria, the induction of TNF
      alpha and IL-6 was observed in RAW 264 cells and Hepa-1.6 cells. Significant
      reduction of TNF-alpha mRNA expression in Hepa-1.6 cells was observed after
      treatment with antibody to TNF-alpha. CONCLUSION: The results obtained in the
      present study show that P. gingivalis extract induces TNF-alpha and IL-6 in an in
      vitro liver model and that macrophage-derived TNF-alpha mediates the induction of
      TNF-alpha in hepatocytes.

PMID- 21895658
TI  - Retinoic acid influences neuronal migration from the ganglionic eminence to the
      cerebral cortex.
AB  - The ganglionic eminence contributes cells to several forebrain structures
      including the cerebral cortex, for which it provides GABAergic interneurons.
      Migration of neuronal precursors from the retinoic-acid rich embryonic ganglionic
      eminence to the cerebral cortex is known to be regulated by several factors, but
      retinoic acid has not been previously implicated. We found retinoic acid to
      potently inhibit cell migration in slice preparations of embryonic mouse
      forebrains, which was reversed by an antagonist of the dopamine-D(2) receptor,
      whose gene is transcriptionally regulated by retinoic acid. Histone-deacetylase
      inhibitors, which amplify nuclear receptor-mediated transcription, potentiated
      the inhibitory effect of retinoic acid. Surprisingly, when retinoic acid
      signalling was completely blocked with a pan-retinoic acid receptor antagonist,
      this also decreased cell migration into the cortex, implying that a minimal level
      of endogenous retinoic acid is necessary for tangential migration. Given these
      opposing effects of retinoic acid in vitro, the in vivo contribution of retinoic
      acid to migration was tested by counting GABAergic interneurons in cortices of
      adult mice with experimental reductions in retinoic acid signalling: a range of
      perturbations resulted in significant reductions in the numerical density of some
      GABAergic interneuron subpopulations. These observations suggest functions of
      retinoic acid in interneuron diversity and organization of cortical excitatory
      inhibitory balance.

PMID- 21895664
TI  - Cenozoic extinctions account for the low diversity of extant gymnosperms compared
      with angiosperms.
AB  - We test the widely held notion that living gymnosperms are 'ancient' and 'living
      fossils' by comparing them with their sister group, the angiosperms. This
      perception derives partly from the lack of gross morphological differences
      between some Mesozoic gymnosperm fossils and their living relatives (e.g. Ginkgo,
      cycads and dawn redwood), suggesting that the rate of evolution of gymnosperms
      has been slow. We estimated the ages and diversification rates of gymnosperm
      lineages using Bayesian relaxed molecular clock dating calibrated with 21
      fossils, based on the phylogenetic analysis of alignments of matK chloroplast DNA
      (cpDNA) and 26S nuclear ribosomal DNA (nrDNA) sequences, and compared these with
      published estimates for angiosperms. Gymnosperm crown groups of Cenozoic age are
      significantly younger than their angiosperm counterparts (median age: 32 Ma vs 50
      Ma) and have long unbranched stems, indicating major extinctions in the Cenozoic,
      in contrast with angiosperms. Surviving gymnosperm genera have diversified more
      slowly than angiosperms during the Neogene as a result of their higher extinction
      rate. Compared with angiosperms, living gymnosperm groups are not ancient. The
      fossil record also indicates that gymnosperms suffered major extinctions when
      climate changed in the Oligocene and Miocene. Extant gymnosperm groups occupy
      diverse habitats and some probably survived after making adaptive shifts.

PMID- 21895662
TI  - Early microbial succession in redeveloping dental biofilms in periodontal health
      and disease.
AB  - BACKGROUND AND OBJECTIVE: The development of dental biofilms after professional
      plaque removal is very rapid. However, it is not clear whether most bacterial
      species return at similar rates in periodontally healthy and periodontitis
      subjects or if there are differences in bacterial recolonization between
      supragingival and subgingival biofilms in periodontal health and disease.
      MATERIAL AND METHODS: Supragingival and subgingival plaque samples were taken
      separately from 28 teeth in 38 healthy and 17 periodontitis subjects immediately
      after professional cleaning. Samples were taken again from seven teeth in
      randomly selected quadrants after 1, 2, 4 and 7 d of no oral hygiene and analyzed
      using checkerboard DNA-DNA hybridization. The percentage of DNA probe counts were
      averaged within subjects at each time-point. Ecological succession was determined
      using a modified moving-window analysis. RESULTS: Succession in supragingival
      biofilms from subjects with periodontitis and from healthy individuals was
      similar. At 1 d, Streptococcus mitis and Neisseria mucosa showed increased
      proportions, followed by Capnocytophaga gingivalis, Eikenella corrodens,
      Veillonella parvula and Streptococcus oralis at 1-4 d. At 4-7 d, Campylobacter
      rectus, Campylobacter showae, Prevotella melaninogenica and Prevotella nigrescens
      became elevated. Subgingival plaque redevelopment was slower and very different
      from supragingival plaque redevelopment. Increased proportions were first
      observed for S. mitis, followed by V. parvula and C. gingivalis and, at 7 d, by
      Capnocytophaga sputigena and P. nigrescens. No significant increase in the
      proportions of periodontal pathogens was observed in any of the clinical groups
      or locations. CONCLUSION: There is a defined order in bacterial species
      succession in early supragingival and subgingival biofilm redevelopment after
      professional cleaning.

PMID- 21895663
TI  - Correlation of cytomegalovirus and human herpesvirus 7 with CD3+ and CD3+ CD4+
      cells in chronic periodontitis patients.
AB  - BACKGROUND AND OBJECTIVE: Human chronic periodontitis is an inflammatory process
      characterized by dense accumulation of immune cells in the periodontal tissue.
      The periodontitis can lead to loss of teeth in the patient and the pathogenesis
      of this disease is not completely known. This study tested the hypothesis that
      chronic periodontitis-affected sites can harbor betaherpesviruses and that
      viruses are linked to a profile of the inflammatory infiltrate. MATERIAL AND
      METHODS: Biopsies of periodontal tissue were taken from periodontitis-affected
      patients and from healthy subjects. Immunohistochemistry was performed to count
      CD19(+) B cells, CD3(+) total T cells, T-CD4(+) and T-CD8(+) cell subsets, and
      PCR was performed to detect cytomegalovirus and human herpesvirus 6 and 7 in the
      samples. One slide of each sample was stained with Giemsa for histopathological
      examination and to evaluate the quality of the cellular infiltrate. RESULTS: As
      expected, tissues collected from healthy subjects presented no significant level
      of inflammatory infiltration and were therefore excluded from immunostaining
      procedures. Results showed that CD19(+) B cells were in higher number than CD3(+)
      T cells in the periodontitis-affected tissue, but this was not statistically
      significant. The T-CD4(+) lymphocyte subset was significantly higher than the T
      CD8(+) lymphocyte subset (p = 0.004) in the samples. Cytomegalovirus and human
      herpesvirus 7 were found at periodontitis-affected sites, but not in tissue
      collected from healthy subjects (p = 0.04 and p = 0.04, respectively). Human
      herpesvirus 6 was rarely detected. We found a correlation between cytomegalovirus
      and lower CD19(+) /CD3(+) ratios (ratio < 0.9, p = 0.003) and between human
      herpesvirus 7 and lower CD19(+) /CD3(+) ratios (ratio < 0.9, p = 0.003) and
      higher CD4(+) /CD8(+) ratios (ratio > 1.1, p = 0.002). CONCLUSION: This study
      shows that cytomegalovirus and human herpesvirus 7 can be present at
      periodontitis-affected sites but are uncommon at healthy periodontal sites.
      Moreover, our data suggest that cytomegalovirus can be related to an inflammatory
      infiltrate with predominance of CD3(+) T cells, whereas human herpesvirus 7 can
      be associated with an infiltrate with predominance of T-CD4(+) cells. However,
      further studies are necessary to support this hypothesis. Herpesviruses could
      play a role in human chronic periodontitis by modulation of the T cell response.

PMID- 21895665
TI  - Photoinduced proton-coupled electron transfers in biorelevant phenolic systems.
AB  - Proton-coupled electron transfer (PCET) reactions have received much attention
      over the past 10 years, from an experimental as well as from a theoretical point
      of view. At the heart of many chemical and biological processes, such reactions
      are of particular interest in energy conversion and enzymatic processes. Among
      the numerous examples of PCET reactions, photosynthesis and particularly
      reactions inside the Photosystem II (PSII) subunit, involving a global four
      electrons and four protons process to perform water oxidation and respiration, is
      the most emblematic one. This review focuses on the photochemical approaches of
      PCET reactions involving phenolic molecules. Indeed, a significant part of
      photochemical PCET studies were conducted on tyrosine or phenol relevant to PSII
      and charge transport in enzymes. The mechanisms of these reactions, sequential or
      concerted, with particular emphasis on the influence of pH, temperature, solvent
      nature and H-bonding pattern are presented based on photochemical techniques and
      related theoretical analysis.

PMID- 21895666
TI  - Theoretical study of electron transfer in Rhodobacter sphaeroides reaction
      center.
AB  - We investigate the substitution effects on electron transfer in Rhodobacter (Rb.)
      sphaeroides reaction center using ab initio calculations. The overlap of
      molecular orbitals in the X-ray structure of 1PCR of the protein data bank using
      Gaussian09 can qualitatively explain the tendency of the experimental transition
      time. The charge effects of proteins on electron transfer in Rb. sphaeroides
      reaction center are also investigated, by employing a simple point charge
      approximation for proteins. We have found that the primary effect for the route A
      orientation is the effect of long side chains. For the route A orientation on the
      electron transfer, the influence of the charges of proteins operates through the
      long side chains indirectly as well as directly work to increase the value of
      overlap integrals.

PMID- 21895667
TI  - Photochemical inactivation of alpha- and poxviruses.
AB  - The objective of this study was to determine whether photochemical inactivation
      of viruses could be accomplished with high efficiency while preserving the
      molecular integrity of viral targets allowing subsequent diagnostic tests to be
      performed at a lower level of containment and cost. We studied the effect of 5
      iodonaphthyl 1-azide (INA) and amotosalen (AMO, also known as S-59), which are
      photochemicals known to target either viral proteins or nucleic acids,
      respectively. We found that vaccinia virus (VACV, an orthopox virus with a DNA
      genome) and pixuna virus (PIXV, an alphavirus with an RNA genome) were stable
      when irradiated with UVA alone or when exposed to either INA or AMO in the dark.
      AMO followed by UVA exposure was at least 1000-fold more virucidal than INA/UVA
      on vaccinia and pixuna viruses treated under similar conditions.
      Photoinactivation with either INA or AMO at conditions that abolished viral
      infectivity resulted in only minimal impairment of subsequent ELISA and PCR
      testing. The results presented in this study should assist in developing methods
      to inactivate in the field environmental and forensic samples suspected of viral
      contamination, thus limiting the need for costly security and safety operations
      after an accidental or intentional viral release.

PMID- 21895668
TI  - Overexpression of SsCHLAPXs confers protection against oxidative stress induced
      by high light in transgenic Arabidopsis thaliana.
AB  - To evaluate the physiological importance of chloroplastic ascorbate peroxidase
      (CHLAPX) in the reactive oxygen species (ROS)-scavenging system of a euhalophyte,
      we cloned the CHLAPX of Suaeda salsa (SsCHLAPX) encoding stromal APX (sAPX) and
      thylakoid-bound APX. The stromal APX of S. salsa (Ss.sAPX) cDNA consists of 1726
      nucleotides including an 1137-bp open reading frame (ORF) and encodes 378 amino
      acids. The thylakoid-bound APX of S. salsa (Ss.tAPX) cDNA consists of 1561
      nucleotides, including a 1284-bp ORF, and encodes 427 amino acids. The N-terminal
      378 amino acids of Ss.sAPX are identical with those of Ss.tAPX, whereas the C
      terminal 49 amino acids differ. Arabidopsis thaliana lines overexpressing Ss.sAPX
      and Ss.tAPX were constructed using Agrobacterium tumefaciens transformation
      methods. Under high light (1000 umol m-2 s-1), malondialdehyde (MDA) content was
      lower in transgenic plants than in the wild type. Under high light, Fv/Fm and
      chlorophyll contents of both overexpressing lines and the wild type declined but
      were significantly higher in the overexpressing lines than in the wild type. The
      activities of APX (EC 1.11.1.11), catalase (CAT 1.11.1.6) and superoxide
      dismutase (SOD EC 1.15.1.1) were higher in the overexpressing lines than in the
      wild type. The transgenic plants showed increased tolerance to oxidative stress
      caused by high light. These results suggest that SsCHLAPX plays an important role
      in scavenging ROS in chloroplasts under stress conditions such as high light.

PMID- 21895669
TI  - Comparison of fructan dynamics in two wheat cultivars with different capacities
      of accumulation and remobilization under drought stress.
AB  - Remobilization of stored carbohydrates in the stem of wheat plants is an
      important contributor to grain filling under drought stress (DS) conditions. A
      massive screening on Iranian wheat cultivars was performed based on stem dry
      weight changes under well-watered and DS conditions. Two cultivars, Shole and
      Crossed Falat Hamun (CFH), with different fructan accumulation and remobilization
      behavior were selected for further studies. Water-soluble carbohydrates (WSCs)
      and fructan metabolizing enzymes were studied both in the stem penultimate and in
      sucrose (Suc) treated, excised leaves. Under drought, CFH produced higher grain
      yields than Shole (412 vs 220 g m(-2)). Also, grain yield loss under drought was
      more limited in CFH than in Shole (17 vs 54%). Under drought, CFH accumulated
      more graminan-type fructo-oligosaccharides than Shole. After anthesis, fructan 6
      exohydrolase (6-FEH; EC 3.2.1.154) activities increased more prominently than
      fructan 1-exohydrolase (EC 3.2.1.153) activities during carbon remobilization.
      Interestingly, CFH showed higher 6-FEH activities in the penultimate than Shole.
      The field experiment results suggest that the combined higher remobilization
      efficiency and high 6-FEH activities in stems of wheat could contribute to grain
      yield under terminal drought. Similar to the penultimate, fructan metabolism
      differed strongly in Suc-treated detached leaves of selected cultivars. This
      suggests that variation in the stem fructan among wheat cultivars grown in the
      field could be traced by leaf blade induction experiments.

PMID- 21895670
TI  - S-methylmethionine is involved in the salinity tolerance of Arabidopsis thaliana
      plants at germination and early growth stages.
AB  - Methionine (Met) is biosynthesized by the activated methyl cycle and S
      methylmethionine (SMM) cycle in one-carbon (C1) metabolism in plants. It is
      converted to S-adenosylmethionine (SAM) which serves as a precursor for many
      metabolites including glycinebetaine, methylated polyols, polyamines and ethylene
      which accumulate in plants in response to salinity. We have investigated how the
      Met biosynthetic pathway is regulated under saline conditions at the
      transcriptional level in Arabidopsis thaliana plants. Within Met biosynthesis
      related genes, the expression of homocysteine methyltransferase (HMT) and
      methionine methyltransferase (MMT) genes in SMM cycle had altered toward
      increasing Met production by the presence of NaCl. We have determined the
      salinity tolerance of an Arabidopsis mmt mutant with an insertional mutation in
      the single copy of the AtMMT gene. Although the mmt mutant showed comparable
      germination and shoot growth with wild type under normal conditions, NaCl
      treatment caused severe repression of germination rate and shoot growth in the
      mmt mutant compared with in the wild type. These results indicate that the
      utilization of SMM is important for the salinity tolerance of Arabidopsis plants
      at the germination and early growth stages.

PMID- 21895671
TI  - Predictors of depressive symptoms among resettled unaccompanied refugee minors.
AB  - This study investigated the level and predictors of depressive symptoms among
      unaccompanied refugee minors after resettlement in Norway. Participants (N = 414)
      were resettled in 26 municipalities from all regions of the country. The average
      length of resettlement time was 3.4 years. They originated from 33 different
      countries, mainly Afghanistan (n = 116), Somalia (n = 74), Sri Lanka (n = 41) and
      Iraq (n = 43). Participants completed a self-report questionnaire administered in
      groups. Findings show that unaccompanied minors are a high-risk group for mental
      health problems also after resettlement in a new country. A multilevel model
      predicting depressive symptoms from individual and contextual demographic factors
      indicated that, controlling for post-traumatic stress, females had more symptoms
      than males and Somalis had fewer symptoms than participants from other countries.
      Variation in symptom levels as a function of gender and ethnic background
      indicates that some groups may have inherent protective or vulnerability factors
      that need to be further studied to understand differences in psychosocial
      adaptation among unaccompanied minors. Further, findings imply that researchers,
      policy makers and mental health care workers need to expand their attention
      beyond the first phases of arrival of unaccompanied asylum seeking and refugee
      minors to the continuing experience of mental health problems after resettlement.

PMID- 21895672
TI  - Causal inference in nonrandomized studies via propensity score methods.

PMID- 21895673
TI  - FCGR3B*03 allele inheritance pattern in Brazilian families and some new variants
      of gene FCGR3B.
AB  - BACKGROUND: The FCGR3B gene encoding the FcyRIIIb receptor for immunoglobulin G
      has three polymorphic forms known as HNA-1a, HNA-1b, and HNA-1c, encoded by the
      alleles FCGR3B*01, FCGR3B*02, and FCGR3B*03, respectively. It is not clear
      whether the inheritance of the FCGR3B*03 allele, which encodes the HNA-1c, is
      linked or not to the other two alleles. The objective of this study was to
      identify the inheritance pattern of the FCGR3B*03 allele in Brazilians. STUDY
      DESIGN AND METHODS: Blood samples from nine families with at least one
      FCGR3B*03(+) member, totalizing 47 individuals, were studied. The presence of the
      FCGR3B*01, FCGR3B*02, and FCGR3B*03 alleles was detected by the polymerase chain
      reaction with sequence-specific priming method, and all DNA samples were
      sequenced. RESULTS: In three of the nine studied families, the FCGR3B*03 was
      passed down with the FCGR3B*02, while in one family the FCGR3B*03 was inherited
      in linkage with FCGR3B*01. The other families were not informative regarding
      FCGR3B*03 inheritance. Sequencing showed for the first time one single-nucleotide
      polymorphism at Position 264 resulting from a simple substitution C->T; three
      other different substitutions at Position 230, T->A, T->G; and the presence of
      three nucleotides at Position 230 (T, G, and A). The previously reported variants
      FCGR3B*01A227G and FCGR3BG330T were also found. CONCLUSION: In this Brazilian
      FCGR3B*03(+) group we found that the inheritance of FCGR3B*03 took place by a
      linkage to FCGR3B*02 or to FCGR3B*01. Linkage of FCGR3B*03 to FCGR3B*02 was the
      most common. Additionally, we report SNPs that have not been described,
      suggesting that they might be more common than previously thought.

PMID- 21895674
TI  - Demographics of apheresis platelet donors in five blood centers in China.
AB  - BACKGROUND: Blood component donations by apheresis has become more common in
      modern blood transfusion practices. However, apheresis donation still remains
      less common in China. This study describes the demographic profile and
      transfusion-transmissible infection (TTI) prevalence among donors making
      apheresis platelet (AP) donations compared to those making whole blood (WB)
      donations and the differences among five geographically diverse blood centers in
      China. STUDY DESIGN AND METHODS: This is a descriptive study using data from all
      successful donations at the five blood centers in 2008 and 2009. Donor
      demographic and TTI screening reactive rates were collected for WB and AP
      donations and blood centers. Logistic regression was used to identify independent
      factors associated with AP donations. RESULTS: From January 1, 2008, to December
      31, 2009, there were 512,594 WB and 26,199 AP donations at five blood centers. AP
      donations accounted for 4.9% of all donations. AP donations have lower reactive
      rate than WB donations for hepatitis B virus surface antigen, hepatitis C virus
      antibodies, human immunodeficiency virus antibodies, and syphilis screening
      testing. Males, donors older than 25 years old, non-Han donors, and donors with
      below high school educational level were more likely to make AP donations. The
      characteristics of AP donations differed among the five Chinese blood centers.
      CONCLUSION: Our analysis suggests that the characteristics of AP donations in
      China are different from WB donations and differ among the five Chinese blood
      centers. Some of the differences are likely due to different recruitment
      policies. Further studies should be conducted to understand what motivates
      Chinese blood donors to participate as AP donors.

PMID- 21895676
TI  - Transfusion-related acute lung injury prevention measures and their impact at
      Canadian Blood Services.
AB  - BACKGROUND: Blood operators have taken measures to reduce transfusion-related
      acute lung injury (TRALI). We classified suspected TRALI cases reported to
      Canadian Blood Services from 2001 to 2009 and assessed the impact of TRALI
      reduction measures. STUDY DESIGN AND METHODS: Using Canadian Consensus Conference
      definitions, cases were reviewed by two experts or, from 2006 to 2009, a TRALI
      Medical Review Group (TMRG). Detection of HLA antibodies was performed using the
      Luminex system starting in 2008. Measures implemented from 2007 to 2009 included
      use of predominantly male plasma, suspension of buffy coat platelets in male
      plasma, and deferral of females with a pregnancy history from plateletpheresis.
      The buffy coat production method was implemented from 2005 to 2008. RESULTS:
      Reporting of all suspected TRALI cases, as well as cases classified as definite
      or possible, increased from 2001 to 2004, was stable from 2004 to 2007, and
      declined in 2008 to 2009. The decline was most marked for plasma-associated
      cases, but occurred for all components. TMRG consensus on classification was
      achieved in 56% of cases. Cases identified as definitive or possible TRALI were
      significantly more likely to have donor antibody against a corresponding
      recipient antigen, compared to other cases. CONCLUSION: Hemovigilance data
      demonstrated an initial increase in TRALI cases, likely due to increased adverse
      event reporting and awareness of TRALI, followed by a decrease in cases related
      to all components. TRALI prevention measures and possibly the switch to the buffy
      coat production method may have contributed to the decline. Classification of
      cases remains challenging.

PMID- 21895675
TI  - Providing ABO-identical platelets and cryoprecipitate to (almost) all patients:
      approach, logistics, and associated decreases in transfusion reaction and red
      blood cell alloimmunization incidence.
AB  - BACKGROUND: There are multiple benefits to transfusing only ABO-identical blood
      components. Historically our institution routinely transfused ABO-nonidentical
      platelets (PLTs) and cryoprecipitate to surgical patients. In April 2005, we
      implemented a policy of transfusing only ABO-identical components whenever
      feasible, regardless of outdating or logistic considerations. STUDY DESIGN AND
      METHODS: Technical staff closely monitored product usage and adjusted blood
      center orders based on recent utilization and planned transfusions. When unable
      to provide ABO-identical PLTs, ABO-compatible PLTs were washed to remove
      incompatible plasma. Data on outdating were collected for 18 months before and
      after implementation. We compared transfusion reaction and red blood cell (RBC)
      alloimmunization incidence for 4 years preceding (2001-2004) and subsequent (2006
      2009) to implementation. RESULTS: In the year after implementation, only 11 of
      410 surgical patients received ABO-nonidentical PLTs (2.7%). There was a 5.6%
      increase in outdating of PLTs. Transfusing ABO-identical components was
      associated with significant reductions in febrile (-46%; 8.0 to 4.3 per 10,000
      components; p < 0.0001) and allergic transfusion reactions (-23%; from 7.0 to 5.4
      per 10,000 components; p = 0.025). A progressive reduction in de novo RBC
      alloimmunization incidence also occurred (-50% by 2009; p = 0.03). CONCLUSIONS:
      Providing ABO-identical PLTs to almost all patients was feasible in our setting
      by changing ordering and inventorying procedures and making the ABO-identical
      policy a staff priority. Unexpected and striking reductions in febrile and
      allergic reactions and RBC alloimmunization were observed, of uncertain causal
      relationship to this ABO policy change, which will require further study.

PMID- 21895677
TI  - Plasticizers excreted in urine: indication of autologous blood transfusion in
      sports.
AB  - BACKGROUND: Misuse of autologous blood transfusions in sports remains
      undetectable. The metabolites of the plasticizer di-(2-ethylhexyl)phthalate
      (DEHP) were recently proposed as markers of blood transfusion, based on high
      urinary concentrations of these compounds observed in patients subjected to blood
      transfusion. This study evaluates DEHP metabolites in urine for detecting
      autologous blood transfusion. STUDY DESIGN AND METHODS: One blood bag was drawn
      from moderately trained subjects and the red blood cells (RBCs) were reinfused
      after different storage periods. Group 1 (12 subjects) was reinfused after 14
      days, and Group 2 (13 subjects), after 28 days of storage. Urine samples were
      collected before and after reinfusion for determination of the concentrations of
      three DEHP metabolites, mono-(2-ethylhexyl)phthalate, mono-(2-ethyl-5
      hydroxyhexyl)phthalate, and mono-(2-ethyl-5-oxohexyl)phthalate. RESULTS:
      Concentrations of DEHP metabolites on the days before reinfusion were in
      agreement with those described after common environmental exposure. A few hours
      after the reinfusion a significant increase was observed for all metabolites in
      all volunteers. Concentrations 1 day later were still higher (p < 0.05) than
      before reinfusion. Variations in urine dilution supported normalization by
      specific gravity. Concentrations of DEHP metabolites tended to be higher after
      longer storage times of RBCs. CONCLUSION: Autologous transfusion with RBCs stored
      in plastic bags provokes an acute increase in the urinary concentrations of DEHP
      metabolites, allowing the detection of this doping malpractice. The window of
      detection is approximately 2 days. The method might be applied to urine samples
      submitted for antidoping testing.

PMID- 21895678
TI  - The outcome of donor screening for human T-cell lymphotropic virus infection in
      The Netherlands.
AB  - BACKGROUND AND OBJECTIVES: Blood donor screening reduces the infectious hazards
      related to blood transfusion, but the range of agents to be screened for is
      debatable. In 1993, the screening of all blood donations for Human T-Cell
      Lymphotropic virus (HTLV) was introduced in The Netherlands. We analysed the
      outcome and costs of HTLV donor screening. METHODS: For the years 2001-2010, the
      number of HTLV infections among new and regular donors was used to estimate the
      prevented number of HTLV-infected donors in the donor pool and the amount of
      morbidity prevented among recipients. RESULTS: Human T-Cell Lymphotropic virus
      screening in The Netherlands detects per year on average 1.4 infected new donors
      and 0.5 infected regular donors. The prevalence among new donors is 30 times
      higher than the incidence among regular donors. Without HTLV screening, 14 HTLV
      infected donors would be donating blood, causing 0.8 to 0.007 cases of HTLV
      disease per year. CONCLUSION: The lack of accurate estimators for infectivity and
      pathogenicity hampers the estimation of morbidity and mortality that HTLV
      infected transfusions would cause. Leucodepletion may be as effective as HTLV
      donor screening; its effect on HTLV transmission should be studied.

PMID- 21895679
TI  - Report of the fourth International Workshop on molecular blood group genotyping.
AB  - The fourth International Society of Blood Transfusion (ISBT) workshop on
      molecular blood group genotyping was held in 2010, with a feedback meeting at the
      ISBT Congress in Berlin, Germany. Fifty laboratories participated, 17 more than
      in 2008. Six samples were distributed. Samples 1-3 were DNA samples for all red
      cell blood group tests available to the participants. Of the 46 laboratories that
      tested these samples, 37 obtained completely correct results, although the extent
      of testing varied considerably. Sample 4, also a DNA sample, was an Rh problem in
      which RHDPsi and RHCE*ceCF were present, but the participants were only informed
      that the donor's red cells typed as positive with some monoclonal anti-D. Of the
      42 laboratories that participated in this exercise, seven performed the
      sequencing necessary to obtain the correct result. Samples 5 and 6 were plasma
      samples from RhD-negative pregnant women, for foetal RhD testing. These were sent
      to 25 laboratories, and two incorrect results were reported. Overall, the level
      of accuracy was about equal to that of the previous workshop. The main conclusion
      for the last two workshops can be reiterated: with greater care and attention to
      detail, very high standards could be set for molecular blood group genotyping.

PMID- 21895680
TI  - Molecularly cloned SHIV-CN97001: a replication-competent, R5 simian/human
      immunodeficiency virus containing env of a primary Chinese HIV-1 clade C isolate.
AB  - BACKGROUND: The increasing prevalence of human immunodeficiency virus type 1 (HIV
      1) subtype C infection worldwide calls for efforts to develop a relevant animal
      model for evaluating AIDS candidate vaccines. In China, the prevalent HIV strains
      comprise a circulating recombinant form, BC (CRF07_BC), in which the envelope
      belongs to subtype C. METHODS: To evaluate potential AIDS vaccines targeting
      Chinese viral strains in non-human primate models, we constructed a simian/human
      immunodeficiency virus (SHIV) carrying most of the envelope sequence of a primary
      HIV-1 clade C strain isolated from an HIV-positive intravenous drug user from
      YunNan province in China. Furthermore, to determine whether in vivo adaptation
      would enhance the infectivity of SHIV-CN97001, the parental infectious strain was
      serially passaged through eight Chinese rhesus macaques. RESULTS: Infection of
      six Chinese rhesus macaques with SHIV-CN97001 resulted in a low level of viremia
      and no significant alteration in CD4+ T-lymphocyte counts. However, the hallmarks
      of SHIV infectivity developed gradually, as shown by the increasingly elevated
      peak viremia with each passage. CONCLUSION: These findings establish that the R5
      tropic SHIV-CN97001/Chinese rhesus macaque model should be very useful for the
      evaluation of HIV-1 subtype C vaccines in China.

PMID- 21895681
TI  - Pancreas anatomy and surgical procedure for pancreatectomy in rhesus monkeys.
AB  - BACKGROUND: The aim of this study was to investigate the pancreas anatomy and
      surgical procedure for harvesting pancreas for islet isolation while performing
      pancreatectomy to induce diabetes in rhesus monkeys. METHODS: The necropsy was
      performed in three cadaveric monkeys. Two monkeys underwent the total
      pancreatectomy and four underwent partial pancreatectomy (70-75%). RESULTS: The
      greater omentum without ligament to transverse colon, the cystic artery arising
      from the proper hepatic artery and the branches supplying the paries posterior
      gastricus from the splenic artery were observed. For pancreatectomy, resected
      pancreas can be used for islet isolation. Diabetes was not induced in the monkeys
      undergoing partial pancreatectomy (70-75%). CONCLUSIONS: Pancreas anatomy in
      rhesus monkeys is not the same as in human. Diabetes can be induced in rhesus
      monkeys by total but not partial pancreatectomy (70-75%). Resected pancreas can
      be used for islet isolation while performing pancreatectomy to induce diabetes.

PMID- 21895682
TI  - Residue iteration decomposition (RIDE): A new method to separate ERP components
      on the basis of latency variability in single trials.
AB  - Event-related brain potentials (ERPs) are important research tools because they
      provide insights into mental processing at high temporal resolution. Their
      usefulness, however, is limited by the need to average over a large number of
      trials, sacrificing information about the trial-by-trial variability of latencies
      or amplitudes of specific ERP components. Here we propose a novel method based on
      an iteration strategy of the residues of averaged ERPs (RIDE) to separate latency
      variable component clusters. The separated component clusters can then serve as
      templates to estimate latencies in single trials with high precision. By applying
      RIDE to data from a face-priming experiment, we separate priming effects and show
      that they are robust against latency shifts and within-condition variability.
      RIDE is useful for a variety of data sets that show different degrees of
      variability and temporal overlap between ERP components.

PMID- 21895683
TI  - Mass univariate analysis of event-related brain potentials/fields I: a critical
      tutorial review.
AB  - Event-related potentials (ERPs) and magnetic fields (ERFs) are typically analyzed
      via ANOVAs on mean activity in a priori windows. Advances in computing power and
      statistics have produced an alternative, mass univariate analyses consisting of
      thousands of statistical tests and powerful corrections for multiple comparisons.
      Such analyses are most useful when one has little a priori knowledge of effect
      locations or latencies, and for delineating effect boundaries. Mass univariate
      analyses complement and, at times, obviate traditional analyses. Here we review
      this approach as applied to ERP/ERF data and four methods for multiple comparison
      correction: strong control of the familywise error rate (FWER) via permutation
      tests, weak control of FWER via cluster-based permutation tests, false discovery
      rate control, and control of the generalized FWER. We end with recommendations
      for their use and introduce free MATLAB software for their implementation.

PMID- 21895684
TI  - Mass univariate analysis of event-related brain potentials/fields II: Simulation
      studies.
AB  - Mass univariate analysis is a relatively new approach for the study of ERPs/ERFs.
      It consists of many statistical tests and one of several powerful corrections for
      multiple comparisons. Multiple comparison corrections differ in their power and
      permissiveness. Moreover, some methods are not guaranteed to work or may be
      overly sensitive to uninteresting deviations from the null hypothesis. Here we
      report the results of simulations assessing the accuracy, permissiveness, and
      power of six popular multiple comparison corrections (permutation-based control
      of the familywise error rate [FWER], weak control of FWER via cluster-based
      permutation tests, permutation-based control of the generalized FWER, and three
      false discovery rate control procedures) using realistic ERP data. In addition,
      we look at the sensitivity of permutation tests to differences in population
      variance. These results will help researchers apply and interpret these
      procedures.

PMID- 21895685
TI  - Relationships between baroreceptor cardiac reflex sensitivity and cognitive
      performance: modulations by gender and blood pressure.
AB  - This study aimed at replicating and extending previous results on the association
      between baroreceptor reflex sensitivity (BRS) and cognitive performance. Thirty
      men and 31 women performed an arithmetic task. After adjusting for numerical
      aptitude and effort, no predictors of performance were found in men. In women,
      the relationships between BRS and parameters related to correct responses were
      modulated by blood pressure (BP). BRS was inversely associated with these
      parameters for participants with BP>1 SD above the mean, whereas the associations
      were positive in participants with BP<1 SD below the mean. Also for women, BRS
      was positively associated with number of errors during the task. These results
      suggest that the relation between BRS and performance varies as a function of the
      type of cognitive processes assessed and that the central nervous system effects
      of the baroreceptors on cognitive functioning are modulated by gender and BP.

PMID- 21895686
TI  - Planning of visually guided reach-to-grasp movements: inference from reaction
      time and contingent negative variation (CNV).
AB  - We performed electroencephalogram (EEG) recording in a precuing task to
      investigate the planning processes of reach-to-grasp movements in human. In this
      reaction time (RT) task, subjects had to reach, grasp, and pull an object as fast
      as possible after a visual GO signal. We manipulated two parameters: the hand
      shape for grasping (precision grip or side grip) and the force required to pull
      the object (high or low). Three seconds before the GO onset, a cue provided
      advance information about force, grip, both parameters, or no information at all.
      EEG data show that reach-to-grasp movements generate differences in the
      topographic distribution of the late Contingent Negative Variation (ICNV)
      amplitude between the 4 precuing conditions. Along with RT data, it confirms that
      two distinct functional networks are involved with different time courses in the
      planning of grip and force. Finally, we outline the composite nature of the lCNV
      that might reflect both high- and low-level planning processes.

PMID- 21895687
TI  - Parsing relationships between dimensions of anxiety and action monitoring brain
      potentials in female undergraduates.
AB  - Anxiety is associated with enhanced action monitoring. Research to date, however,
      has employed extreme group designs that fail to address the full spectrum of
      anxiety, and in which overlapping and co-occurring symptoms obscure the exact
      nature of the relationships between anxiety and action monitoring. To address
      these limitations, relationships between distinct dimensions of anxiety and
      neural indicators of action monitoring were examined in a sample of female
      undergraduates. Results revealed that higher anxious apprehension (i.e., worry)
      was associated with enhanced early action monitoring activity, as indexed by the
      error-related negativity/correct-response negativity. Anxious arousal (i.e.,
      somatic tension) on the other hand, was unrelated to measures of action
      monitoring. These findings suggest that the anxiety-action monitoring link holds
      along the continuum of severity and is specific to the worry component of
      anxiety.

PMID- 21895689
TI  - The role of presleep negative emotion in sleep physiology.
AB  - Although daytime emotional stressful events are often presumed to cause sleep
      disturbances, the few studies of stressful life events on sleep physiology have
      resulted in various and contradictory findings. As research has focused in
      particular on stress in itself, the present study is the first to investigate the
      effect using polysomnography (PSG). Results indicate a significant increase in
      sleep fragmentation, as expressed by decreased sleep efficiency, total sleep
      time, percentage of rapid eye movement (REM) sleep, and an increased wake after
      sleep onset latency, total time awake, latency to SWS, number of awakenings and
      number of awakenings from REM sleep. The results demonstrate that negative
      emotion correlates with enhanced sleep fragmentation helping us to understand why
      sleep patterns change and how sleep disturbances may develop.

PMID- 21895688
TI  - Salivary cortisol and soluble tumor necrosis factor-alpha receptor II responses
      to multiple experimental modalities of acute pain.
AB  - The present study compared cortisol and soluble tumor necrosis factor-alpha
      receptor II (sTNFalphaRII) responses provoked by cold pressor, hot water,
      ischemic, and neutral water (i.e., room temperature) modalities. Oral fluid
      samples were collected before, immediately after, and during recovery to assess
      physiological responses. From baseline, the cold pressor, but not hot water or
      ischemic modalities, produced a significant time-dependent elevation in cortisol,
      whereas cortisol significantly decreased for the neutral water task. When
      compared to baseline, the cold pressor, hot water, and ischemic modalities were
      associated with decreased sTNFalphaRII responses over time. The sTNFalphaRII
      response to neutral water initially decreased but returned to approximate
      baseline levels. Pain ratings were positively associated with cortisol increase
      from baseline and the overall cortisol response was negatively associated with
      the overall sTNFalphaRII response.

PMID- 21895690
TI  - Monitoring force errors: medial-frontal negativity in a unimanual force
      production task.
AB  - The effects of force production on medial-frontal negativity (MFN), reflecting
      the activity of an internal action-monitoring system, were investigated in a
      force-production task. A precue indicated a low or high force before a stimulus
      signaled the execution of the same or opposite force. An incorrectly exerted
      force was assumed to involve an error of force selection if the opposite force
      was required (invalid precue), and an error of force execution if the same force
      was required (valid precue). The task was repeated to examine any improvements in
      monitoring sensitivity. No force-related effects were observed on MFN amplitude.
      Although performance improved, there was no evidence of a force-error sensitive
      monitoring system. As the MFN and motor activity were affected by the precue
      invalidity regardless of the response outcome, the MFN might reflect the activity
      of a general action-evaluation system that is indirectly related to motor
      activation.

PMID- 21895691
TI  - Itches and scratches - is there a link between eczema, ADHD, sleep disruption and
      food hypersensitivity?

PMID- 21895692
TI  - Pharmacokinetics of spinosad and milbemycin oxime administered in combination and
      separately per os to dogs.
AB  - Pharmacokinetic (PK) studies were conducted to determine the potential PK
      interactions when spinosad and milbemycin oxime (MBO) are administered
      simultaneously. Investigations used commercial MBO tablets (C-MBO;
      Interceptor((r)) Flavor Tabs, active ingredient MBO, Novartis Animal Health,
      Greensboro, NC, USA), novel-source (Elanco) MBO (E-MBO) in a gelatin capsule,
      spinosad API (Active Pharmaceutical Ingredient using registered manufacturing
      process) in a gelatin capsule, spinosad tablets (Comfortis((r)) chewable beef
      flavored tablets, active ingredient spinosad, Elanco Animal Health, Greenfield,
      IN, USA), and the recently registered spinosad + E-MBO combination tablets
      (TrifexisTM chewable beef flavored tablets, active ingredients E-MBO and
      spinosad, Elanco Animal Health, Greenfield, IN, USA). Regardless of the source of
      MBO, in the presence of spinosad, greater systemic exposure of MBO was obtained
      as compared to MBO administered alone. Target animal safety studies conducted
      with dose multiples of spinosad and MBO indicate the increased exposure of MBO
      does not have implications on adverse clinical reactions. Further research is
      required to determine whether the higher levels of MBO have any implications for
      improved effectiveness as compared to C-MBO. Effectiveness studies conducted with
      0.5 mg/kg of E-MBO in combination tablets demonstrated noninterference against C
      MBO with both products achieving >99% effectiveness against the dose-limiting
      nematode, Ancylostoma caninum. No statistical differences were detected in the PK
      of MBO when comparing animals receiving E-MBO (without spinosad) and C-MBO. Also,
      the PK of spinosad was unaltered when co-administered with MBO.

PMID- 21895693
TI  - The effects of simulated rain and sun exposure on the plasma disposition of
      ivermectin following pour-on administration in heifers.

PMID- 21895694
TI  - Overexpression of constitutively active Arabidopsis RabG3b promotes xylem
      development in transgenic poplars.
AB  - An Arabidopsis small GTPase, RabG3b, was previously characterized as a component
      of autophagy and as a positive regulator for xylem development in Arabidopsis. In
      this work, we assessed whether RabG3b modulates xylem-associated traits in poplar
      in a similar way as in Arabidopsis. We generated transgenic poplars (Populus alba
      * Populus tremula var. glandulosa) overexpressing a constitutively active form of
      RabG3b (RabG3bCA) and performed a range of morphological, histochemical and
      molecular analyses to examine xylogenesis. RabG3bCA transgenic poplars showed
      increased stem growth due to enhanced xylem development. Autophagic structures
      were observed in differentiating xyelm cells undergoing programmed cell death
      (PCD) in wild-type poplar, and were more abundant in RabG3bCA transgenic poplar
      plants and cultured cells. Xylogenic activation was also accompanied by the
      expression of secondary wall-, PCD- and autophagy-related genes. Collectively,
      our results suggest that Arabidopsis RabG3b functions to regulate xylem growth
      through the activation of autophagy during wood formation in Populus, as does the
      same in Arabidopsis.

PMID- 21895695
TI  - Silencing of G proteins uncovers diversified plant responses when challenged by
      three elicitors in Nicotiana benthamiana.
AB  - Signalling through heterotrimeric G protein composed of alpha-, beta- and gamma
      subunits is essential in numerous physiological processes. Here we show that this
      prototypical G protein complex acts mechanistically by controlling elicitor
      sensitivity towards hypersensitive response (HR) and stomatal closure in
      Nicotiana benthamiana. Galpha-, Gbeta1-, and Gbeta2-silenced plants were
      generated using virus-induced gene silencing. All silenced plants were treated
      with Xanthomonas oryzae harpin, Magnaporthe oryzae Nep1 and Phytophthora
      boehmeriae boehmerin, respectively. HR was dramatically impaired in Galpha- and
      Gbeta2-silenced plants treated with harpin, indicating that harpin-, rather than
      Nep1- or boehmerin-triggered HR, is Galpha- and Gbeta2-dependent. Moreover, all
      Galpha-, Gbeta1- and Gbeta2-silenced plants significantly impaired elicitor
      induced stomatal closure, elicitor-promoted nitric oxide (NO) production and
      active oxygen species accumulation in guard cells. To our knowledge, this is the
      first report of Galpha and Gbeta subunits involvement in stomatal closure in
      response to elicitors. Furthermore, silencing of Galpha, Gbeta1 and Gbeta2 has an
      effect on the transcription of plant defence-related genes when challenged by
      three elicitors. In conclusion, silencing of G protein subunits results in many
      interesting plant cell responses, revealing that plant immunity systems employ
      both conserved and distinct G protein pathways to sense elicitors from distinct
      phytopathogens formed during plant-microbe evolution.

PMID- 21895696
TI  - Genome-wide identification of Medicago truncatula microRNAs and their targets
      reveals their differential regulation by heavy metal.
AB  - We adopted a deep sequencing approach developed by Solexa (Illumina Inc., San
      Diego, CA, USA) to investigate global expression and complexity of microRNAs
      (miRNAs) and their targets from Medicago truncatula. Two small RNA libraries and
      two degradome libraries were constructed from mercury (Hg)-treated and Hg-free M.
      truncatula seedlings. For miRNAs, each library generated 18.5-18.6 million short
      sequences, resulting in 10.2-10.8 million clean reads. At least 52 new miRNA
      candidates with ~ 21 nucleotides are perfectly matched to the M. truncatula
      genome. Statistical analysis on transcript abundance of the new candidate miRNAs
      revealed that most of them were differentially regulated by the heavy metal
      mercury Hg(II), with 12 miRNAs being specifically induced by Hg exposure.
      Additionally, we identified 201 individual miRNAs representing 63 known M.
      truncatula miRNA families, including 12 new conserved and one non-conserved
      miRNAs that have not been described before. Finally, 130 targets for 58 known (37
      conserved and 21 non-conserved) miRNA families and 37 targets for 18 new M.
      truncatula-specific candidate miRNA families were identified by high-throughput
      degradome sequencing approach.

PMID- 21895697
TI  - Day/night regulation of aquaporins during the CAM cycle in Mesembryanthemum
      crystallinum.
AB  - Mesembryanthemum crystallinum exhibits induction of Crassulacean acid metabolism
      (CAM) after a threshold stage of development, by exposure to long days with high
      light intensities or by water and salt stress. During the CAM cycle, fluctuations
      in carbon partitioning within the cell lead to transient drops in osmotic
      potential, which are likely stabilized/balanced by passive movement of water via
      aquaporins (AQPs). Protoplast swelling assays were used to detect changes in
      water permeability during the day/night cycle of CAM. To assess the role of AQPs
      during the same period, we followed transcript accumulation and protein abundance
      of four plasma membrane intrinsic proteins (PIPs) and one tonoplast intrinsic
      protein (TIP). CAM plants showed a persistent rhythm of specific AQP protein
      abundance changes throughout the day/night cycle, including changes in amount of
      McPIP2;1, McTIP1;2, McPIP1;4 and McPIP1;5, while the abundance of McPIP1;2 was
      unchanged. These protein changes did not appear to be coordinated with transcript
      levels for any of the AQPs analysed; however, they did occur in parrallel to
      alterations in water permeability, as well as variations in cell osmolarity,
      pinitol, glucose, fructose and phosphoenolpyruvate carboxylase (PEPc) levels
      measured throughout the day/night CAM cycle. Results suggest a role for AQPs in
      maintaining water balance during CAM and highlight the complexity of protein
      expression during the CAM cycle.

PMID- 21895698
TI  - Sulfite oxidase controls sulfur metabolism under SO2 exposure in Arabidopsis
      thaliana.
AB  - In the present study, the significance of sulfite oxidase (SO) for sulfite
      detoxification and sulfur assimilation was investigated. In response to sulfur
      dioxide (SO(2)) exposure, a remarkable expansion of sulfate and a significant
      increase of GSH pool were observed in wild-type and SO-overexpressing
      Arabidopsis. These metabolic changes were connected with a negative feedback
      inhibition of adenosine 5'-phosphosulfate reductase (APR), but no alterations in
      gas exchange parameters or visible symptoms of injury. However, Arabidopsis SO-KO
      mutants were consistently negatively affected upon 600 nL L(-1) SO(2) exposure
      for 60 h and showed phenotypical symptoms of injury with small necrotic spots on
      the leaves. The mean g(H2O) was reduced by about 60% over the fumigation period,
      accompanied by a reduction of net CO(2) assimilation and SO(2) uptake of about 50
      and 35%. Moreover, sulfur metabolism was completely distorted. Whereas sulfate
      pool was kept constant, thiol-levels strongly increased. This demonstrates that
      SO should be the only protagonist for back-oxidizing and detoxification of
      sulfite. Based on these results, it is suggested that co-regulation of SO and APR
      controls sulfate assimilation pathway and stabilizes sulfite distribution into
      organic sulfur compounds. In conclusion, a sulfate-sulfite cycle driven by APR
      and SO can be postulated for fine-tuning of sulfur distribution that is
      additionally used for sulfite detoxification, when plants are exposed to
      atmospheric SO(2).

PMID- 21895699
TI  - Hydraulic architecture of two species differing in wood density: opposing
      strategies in co-occurring tropical pioneer trees.
AB  - Co-occurring species often have different strategies for tolerating daily cycles
      of water stress. One underlying parameter that can link together the suite of
      traits that enables a given strategy is wood density. Here we compare hydraulic
      traits of two pioneer species from a tropical forest in Panama that differ in
      wood density: Miconia argentea and Anacardium excelsum. As hypothesized, the
      higher wood density of Miconia was associated with smaller diameter vessels and
      fibres, more water stress-resistant leaves and stems, and roughly half the
      capacitance of the lower wood density Anacardium. However, the scaling of
      hydraulic parameters such as the increases in leaf area and measures of hydraulic
      conductivity with stem diameter was remarkably similar between the two species.
      The collection of traits exhibited by Miconia allowed it to tolerate more water
      stress than Anacardium, which relied more heavily on its capacitance to buffer
      daily water potential fluctuations. This work demonstrates the importance of
      examining a range of hydraulic traits throughout the plant and highlights the
      spectrum of possible strategies for coping with daily and seasonal water stress
      cycles.

PMID- 21895700
TI  - Push-out bond strength of two new calcium silicate-based endodontic sealers to
      root canal dentine.
AB  - AIM: To assess the push-out bond strength of two new calcium silicate-based
      endodontic sealers in the root canals of extracted teeth. METHODOLOGY: Thirty
      extracted single-rooted central incisors of similar sizes were selected randomly
      and distributed to three groups (n = 10). All canals were instrumented using
      ProTaper rotary instruments to achieve tapered canal walls. Irrigation was
      performed using 5 mL 2.5% NaOCl between each instrument, and the smear layer was
      removed using 5 mL 17% EDTA. The canals were filled with three different sealers
      using a cold lateral compaction technique: group 1: AH Plus + gutta-percha, group
      2: I Root SP + gutta-percha and group 3: MTA Fillapex + gutta-percha. Three
      horizontal sections were prepared at a thickness of 1 mm +/- 0.1 in the apical,
      middle and coronal parts of each root. The test specimens were subjected to the
      push-out test method using a Universal Test Machine (Instron, Canton, MA, USA)
      that carried 1-mm, 0.5-mm and 0.3-mm plungers for coronal, middle and apical
      specimens, respectively. The loading speed was 1 mm min(-1) . The push-out data
      were analysed by two-way analysis of variance (anova) and the post hoc Holm-Sidak
      test, with significance set at P < 0.05. RESULTS: In the coronal specimens, there
      was no significant difference between the sealers. In the middle and apical
      segments, there was no significant difference between I Root SP and AH Plus
      groups. However, the I Root SP and AH Plus had significantly higher bond strength
      values than the MTA Fillapex (P < 0.05). In terms of root segments, the bond
      strengths in the middle specimens and the apical specimens were higher compared
      with the bond strengths in the coronal specimens (P < 0.05). There were no
      significant differences between the bond strengths in the middle and apical
      specimens. CONCLUSION: MTA Fillapex had the lowest push-out bond values to root
      dentine compared with other sealers.

PMID- 21895701
TI  - Diagnostic accuracy of limited-volume cone-beam computed tomography in the
      detection of periapical bone loss: 360 degrees  scans versus 180 degrees  scans.
AB  - AIM: To investigate the effect of reducing limited-volume cone-beam computed
      tomographs arc of rotation from 360 degrees  to 180 degrees  on the ability to
      diagnose small, artificially created apical lesions. METHODOLOGY: Small,
      artificial apical bone lesions were prepared with a bur in the apical region of
      the distal root of ten mandibular first molars, in human dry mandibles. The jaws
      were scanned in a fixed position with limited-volume CBCT making a 360 degrees 
      and 180 degrees  arc of rotation, before and after each periapical lesion had
      been created. A 4 * 4 cm field of view was used at 90 kV, with a current of 4 mA.
      Ten examiners blinded to the scan parameters and controls scored the
      presence/absence of bone lesions. Intra-examiner reliability was determined after
      2 weeks, reviewing half the data set. Statistical analyses with paired t-tests
      determined the diagnostic accuracy of the two modalities (360 degrees  vs. 180
      degrees ) in terms of sensitivity, specificity, receiver operating characteristic
      area under the curve, positive predictive values and negative predictive values.
      RESULTS: The mean values for sensitivity of the 360 degrees  and 180 degrees 
      scans were 0.91 and 0.89, respectively; their mean specificities were 0.73. No
      significant differences were reflected in the statistical analyses. CONCLUSIONS:
      Both 360 degrees  and 180 degrees  cone-beam computed tomography scans yielded
      similar accuracy in the detection of artificial bone lesions. The use of 180
      degrees  scans might be advisable to reduce the radiation dose to the patient in
      line with the ICRP guidance to use as low a dosage as reasonably achievable.

PMID- 21895702
TI  - Antibacterial activity of two MTA-based root canal sealers.
AB  - AIM: To evaluate the pH and antibacterial activity of Endo CPM Sealer and MTA
      Fillapex by two different methods, using white MTA and Endofill as references for
      comparison. METHODOLOGY: Antibacterial activity was evaluated against
      Enterococcus faecalis (ATCC 29212). The agar diffusion test (ADT) was performed
      to evaluate the effect before setting. The materials were placed in four
      equidistant wells made in ten agar plates. After incubation at 37  degrees C for
      48 h, the inhibition zones were measured using a digital paquimeter. The direct
      contact test (DCT) was performed to assess the antibacterial effect after
      setting. Suspensions of crushed materials were prepared and mixed with E.
      faecalis. After different periods of time (1, 6, 15 and 60 min), the survival of
      bacteria was assessed by using 10-fold serial dilution and cultivated on agar
      plates in triplicate. Colony-forming units (CFU) mL(-1) were calculated after
      incubation. pH values were also measured in triplicate. Comparison between
      sealers in the ADT and DCT was performed by the Kruskal-Wallis test. RESULTS: In
      the ADT, inhibition zones were found with MTA Fillapex and Endofill. They were
      similar to each other and greater than the other sealers (P < 0.05). None of the
      tested sealers demonstrated antibacterial activity in the DCT, and thus, all
      sealers had similar bacterial counts compared with the negative control group (P
      > 0.05). White MTA and Endo CPM Sealer suspensions had pH values >11, whilst MTA
      Fillapex and Endofill had lower values. CONCLUSIONS: MTA Fillapex and Endofill
      had an antibacterial effect against E. faecalis before setting, but none of the
      sealers maintained antibacterial activity after setting, despite the high pH of
      the MTA-based materials.

PMID- 21895703
TI  - Medico-legal aspects of vertical root fractures in root filled teeth.
AB  - AIM:   To analyse the medico-legal aspects of vertical root fracture (VRF)
      following root canal treatment (RCT). METHODOLOGY:   A comprehensive search in a
      professional liability insurance database was conducted to retrospectively
      identify cases of VRF following RCT. The complaints were categorized as either
      financial risk bearing or financial nonrisk bearing, and related demographic,
      prosthetic and endodontic variables were analysed. RESULTS:   Seventy-seven legal
      cases of patients with VRFs following RCT were identified. Most of the cases were
      either in premolars or in mandibular molar teeth (P<0.05). Poor-quality root
      filling was associated with an extended delay of diagnosis (P<0.05). The presence
      of a post significantly increased the financial risk assessment (P<0.05).
      CONCLUSIONS:   Poor quality root fillings complicate the diagnosis of VRF, which
      in turn extends the time for achieving an accurate diagnosis and increasing the
      medico-legal risk. Premolar and mandibular molar teeth were more prone to medico
      legal claims related to VRF following RCT. Post should be placed only when
      essential for additional core support to avoid medico-legal risk.

PMID- 21895704
TI  - Cross-ethnic friendships, perceived discrimination, and their effects on ethnic
      activism over time: a longitudinal investigation of three ethnic minority groups.
AB  - This research examines cross-ethnic friendships as a predictor of perceived
      discrimination and support for ethnic activism over time among African American,
      Latino American, and Asian American undergraduate participants from a multi-year,
      longitudinal study conducted in the United States. Our research builds on prior
      cross-sectional research by testing effects longitudinally and examining how
      relationships among these variables may differ across ethnic minority groups.
      Results indicate that, over time, greater friendships with Whites predict both
      lower perceptions of discrimination and less support for ethnic activism among
      African Americans and Latino Americans, but not among Asian Americans.
      Implications of these findings for future research on inter-group contact,
      minority-majority relations, and ethnic group differences in status are
      discussed.

PMID- 21895705
TI  - When East meets West: a longitudinal examination of the relationship between
      group relative deprivation and intergroup contact in reunified Germany.
AB  - Intergroup contact and group relative deprivation have both been shown to play a
      key role in the understanding of intergroup relations. Nevertheless, we know
      little about their causal relationship. In order to shed some light on the
      directionality and causality of the relationship between intergroup contact and
      group relative deprivation, we analysed responses by East and West Germans from
      k= 97 different cities, collected 6 (N(T)(1) = 1,001), 8 (N(T)(2) = 747), and 10
      years (N(T)(3) = 565) after reunification. Multi-level cross-lagged analyses
      showed that group relative deprivation at T1 led to more (rather than less)
      intergroup contact between East and West Germans 2 years as well as 4 years
      later. We found no evidence for the reverse causal relationship, or moderation by
      group membership. Furthermore, admiration mediated the positive effect of
      relative deprivation on intergroup contact for both East and West Germans. This
      intriguing finding suggests that intergroup contact may be used as a proactive
      identity management strategy by members of both minority and majority groups.

PMID- 21895706
TI  - When scoring algorithms matter: effects of working memory load on different IAT
      scores.
AB  - In most process accounts of the Implicit Association Test (IAT), it is assumed
      that compatible and incompatible IAT blocks require different amounts of working
      memory capacity (WMC) and recruit executive functions such as task switching and
      inhibition to different extents. In the present study (N= 120), cognitive load
      during the completion of an IAT was experimentally manipulated by means of an
      oral random-number generation secondary task. Cognitive load led to slower
      latencies and more errors, especially in the incompatible block. However,
      different IAT scores, including conventional scores and D-scores, were affected
      differentially by the load manipulation: scores based on raw data of task
      performance such as latencies and errors were increased whereas scores that use
      transformations such as log-latency scores and D-scores were decreased. A number
      of analyses shed light on the reasons for the unexpected dissociation between
      scoring algorithms. Remarkably, external correlations of the IAT scores were not
      affected by the experimental manipulation.

PMID- 21895707
TI  - Identity and attitudinal reactions to perceptions of inter-group interactions
      among ethnic migrants: a longitudinal study.
AB  - This 1-year follow-up study investigated the direct and indirect effects of past,
      anticipated, and actual experiences of inter-group interactions on the
      development of national identity and attitudes towards the national majority
      among ethnic re-migrants (N= 141) from Russia to Finland. According to the
      results, the quality of past inter-group contact in the pre-migration stage
      (T(1)) did not directly affect national identification and out-group attitudes in
      the post-migration stage (T(2)). Instead, the effect of contact quality at T(1)
      on national identification and out-group attitudes at T(2) was indirect via
      perceived discrimination and out-group rejection at T(2). In addition, there were
      two indirect pathways from out-group attitudes at T(1) to national identification
      and out-group attitudes at T(2), via pleasant contact experiences (further
      associated with positive out-group attitudes) and via perceived discrimination
      (further associated with negative attitudes and lower national identification) in
      the post-migration stage. Anticipated discrimination only had a direct effect on
      out-group attitudes in the post-migration stage. The results highlight the role
      of past and anticipated inter-group relations in the formation of post-migration
      inter-group interactions, which, in turn, are decisive for the formation of
      national identification and out-group attitudes of re-migrants.

PMID- 21895708
TI  - Alcohol dependence is related to overall internalizing psychopathology load
      rather than to particular internalizing disorders: evidence from a national
      sample.
AB  - BACKGROUND: Alcohol dependence is more prevalent among those with any one of
      several anxiety or depressive ("internalizing") disorders than among those in the
      general population. However, because internalizing disorders are highly
      intercorrelated, it is ambiguous whether alcohol dependence is related to
      internalizing psychopathology components that are: (i) unique to a particular
      internalizing disorder ("specific"); versus (ii) shared across a number of
      internalizing disorders ("general"). To clarify this ambiguity, we employed
      structural equation and logistic models to decompose the specific versus general
      components of internalizing psychopathology and then related these components
      separately to alcohol dependence. METHODS: The data were based on face-to-face
      interviews of U.S. community residents collected in the 2001 to 2002 National
      Epidemiologic Survey on Alcohol and Related Conditions (NESARC; N = 43,093).
      RESULTS: Both analytic approaches demonstrated that increases in the general
      internalizing psychopathology load are accompanied by increases in the prevalence
      of alcohol dependence. Once the general internalizing psychopathology load is
      accounted for, knowing whether a particular internalizing disorder is present or
      absent provides little additional information regarding the prevalence of alcohol
      dependence. CONCLUSIONS: The components of internalizing psychopathology that are
      associated with alcohol dependence are shared and cumulative among common anxiety
      and depressive disorders. These findings have the potential to influence clinical
      and scientific conceptualizations of the association between alcohol dependence
      and internalizing psychopathology.

PMID- 21895709
TI  - The biometric measurement of alcohol consumption.
AB  - BACKGROUND: Proper ascertainment of the history of alcohol consumption by an
      individual is an important component of medical diagnosis of disease and
      influences the implementation of appropriate treatment strategies that include
      prescription of medication, as well as intervention for the negative physical and
      social consequences of hazardous/harmful levels of alcohol consumption.
      Biological (biometric) diagnostic tests that provide information on current and
      past quantity and frequency of alcohol consumption by an individual, prior to
      onset of organ damage, continue to be sought. METHODS: Platelet monoamine oxidase
      B (MAO-B) protein was quantitated in 2 populations of subjects who had histories
      of different levels of alcohol consumption. Levels were assayed by immunoblotting
      or by ELISA. The development and evaluation of the new ELISA-based measure of
      platelet MAO-B protein levels is described. RESULTS: One subject population
      constituted a nontreatment-seeking, cross-sectional subject sample, and the other
      population was a longitudinally followed, hospitalized group of subjects. An
      algorithm combining measures of platelet MAO-B protein with the plasma levels of
      carbohydrate-deficient transferrin (CDT) and with liver enzymes (aspartate
      aminotransferase or gamma-glutamyltransferase [GGT]) can detect hazardous/harmful
      alcohol use (HHAU) with the highest sensitivity and specificity in the cross
      sectional nontreatment-seeking population. In the treatment-seeking population,
      low MAO-B protein levels at admission are associated with heavy drinking prior to
      admission, and these protein levels increase over a period of abstinence from
      alcohol. CONCLUSIONS: The platelet MAO-B protein measurement is particularly
      effective for male alcohol consumers. The combined use of MAO-B protein measures
      together with measures of CDT and GGT does, however, improve the diagnostic
      utility of both markers for ascertaining HHAU in women. Furthermore, measurement
      of changes in platelet MAO-B protein levels during treatment for alcohol
      dependence may help monitor the success of the treatment program.

PMID- 21895710
TI  - Reward and relapse: complete gene-induced dissociation in an animal model of
      alcohol dependence.
AB  - BACKGROUND: In animal models of continuous alcohol self-administration, in which
      physical dependence does not constitute the major factor of ethanol intake, 2
      factors likely contribute to the perpetuation of alcohol self-administration: (i)
      the rewarding effects of ethanol and (ii) the contextual conditioning cues that
      exist along with the process of self-administration. Present studies are aimed at
      understanding the relative contribution of these factors on the perpetuation of
      heavy alcohol self-administration, as an indication of relapse. METHODS: Wistar
      derived UChB high ethanol drinker rats were allowed access to 10% ethanol and
      water on a 24-hour basis. In initial studies, an anticatalase shRNA gene-coding
      lentiviral vector aimed at inhibiting acetaldehyde generation was administered
      into the ventral tegmental area (VTA) of the animals prior to ethanol access. In
      subsequent studies, the lentiviral vector was administered to animals, which had
      consumed ethanol on a 24-hour basis, or a 1-hour basis, after the animals had
      reached high levels of ethanol intake for 60 to 80 days. In final studies,
      quinine (0.01%) was added to the ethanol solution to alter the conditioning
      taste/smell cues of alcohol that animals had chronically ingested. RESULTS: Data
      indicate that the administration of an anticatalase vector into the VTA of naive
      animals blocked reward and alcohol self-administration, while it was,
      nevertheless, inactive in inhibiting alcohol self-administration in rats that had
      been conditioned to ingest ethanol for over 2 months. The lack of inhibitory
      effect of the anticatalase vector on ethanol intake in animals that had
      chronically self-administered ethanol was fully reversed when the contextual
      conditioning cues of the alcohol solution were changed. CONCLUSIONS: Data
      highlight the importance of conditioning factors in relapse and suggest that only
      abolishing or blunting it, along with long-lasting pharmacological treatment to
      reduce ethanol reward, may have protracted effects in reducing alcohol self
      administration.

PMID- 21895711
TI  - Ethanol-induced oxidative stress via the CYP2E1 pathway disrupts adiponectin
      secretion from adipocytes.
AB  - BACKGROUND: Adipose tissue is an important target for ethanol action. One
      important effect of ethanol is to reduce the secretion of adiponectin from
      adipocytes; this decrease is associated with lowered circulating adiponectin in
      rodent models of chronic ethanol feeding. Adiponectin is an insulin-sensitizing,
      anti-inflammatory adipokine; decreased adiponectin activity may contribute to
      tissue injury in response to chronic ethanol. Here, we investigated the role of
      cytochrome P450 2E1 (CYP2E1) and oxidative stress in the mechanism for impaired
      adiponectin secretion from adipocytes in response to ethanol. METHODS: Male
      Wistar rats were fed a liquid diet containing ethanol as 36% of calories or pair
      fed a control diet for 4 weeks. 3T3-L1 adipocyte cultures, expressing CYP2E1 or
      not, were exposed to ethanol or 4-hydroxynonenal (4-HNE). RESULTS: Chronic
      ethanol feeding to rats suppressed the secretion of adiponectin from isolated
      epididymal adipocytes. Ethanol feeding induced the expression of CYP2E1 in
      adipocytes and increased markers of oxidative stress, including 4-HNE and protein
      carbonyls. Because adiponectin is posttranslationally processed in the
      endoplasmic reticulum and Golgi, we investigated the impact of ethanol on the
      redox status of high-density microsomes. Chronic ethanol decreased the ratio of
      reduced glutathione to oxidized glutathione (4.6:1, pair-fed; 2.9:1, ethanol-fed)
      in high-density microsomes isolated from rat epididymal adipose tissue. We next
      utilized the 3T3-L1 adipocyte-like cell model to interrogate the mechanisms for
      impaired adiponectin secretion. Culture of 3T3-L1 adipocytes overexpressing
      exogenous CYP2E1, but not those overexpressing antisense CYP2E1, with ethanol
      increased oxidative stress and impaired adiponectin secretion from intracellular
      pools. Consistent with a role of oxidative stress in impaired adiponectin
      secretion, challenge of 3T3-L1 adipocytes with 4-HNE also reduced adiponectin
      mRNA expression and secretion, without affecting intracellular adiponectin
      concentration. CONCLUSIONS: These data demonstrate that CYP2E1-dependent reactive
      oxygen species production in response to ethanol disrupts adiponectin secretion
      from adipocytes.

PMID- 21895712
TI  - Comparison of alcoholism subtypes as moderators of the response to sertraline
      treatment.
AB  - BACKGROUND: A variety of typologies have been used to categorize alcoholism's
      diverse manifestations. Although the most widely studied typologies are
      dichotomous ones based on genetic epidemiologic findings or using cluster
      analytic methods, recent efforts have utilized a single item or the onset of a
      diagnosis of alcohol dependence to subtype individuals based on the age of
      alcoholism onset. We compared 3 different methods to subtype alcoholics. METHODS:
      This secondary analysis used data from 134 alcohol-dependent participants in a
      placebo-controlled trial of sertraline (Kranzler et al., 2011). We compared
      cluster analysis to distinguish 2 risk/severity subtypes (Babor et al., 1992)
      with 2 age-of-onset subtypes (i.e., based on the age of onset of problem drinking
      or the age at which alcohol dependence criteria were first met). RESULTS: Each
      method yielded subgroups that differed significantly from one another on
      demographic and clinical measures. Although concordance was high between the 2
      age-of-onset methods, it was poor between the age-of-onset methods and the
      cluster analysis-derived approach. All 3 subtyping approaches significantly
      moderated the effects of sertraline or placebo, but only in the L'L' genotype
      group, as originally reported (Kranzler et al., 2011). In all cases, sertraline
      treatment was superior to placebo in later-onset individuals and inferior to
      placebo in the earlier-onset groups. CONCLUSIONS: Because age-of-onset subtypes
      can be defined retrospectively on an individual basis, they may be more
      clinically useful than cluster-derived subtypes, which require group data.
      Because the 2 age-of-onset measures we examined appear to have comparable
      validity, a single item is easier to use as a measure of the age of onset of
      problem drinking.

PMID- 21895714
TI  - Opioidergic modulation of ethanol self-administration in the ventral pallidum.
AB  - BACKGROUND: Striatopallidal medium spiny neurons have been viewed as a final
      common path for drug reward and the ventral pallidum as an essential convergent
      point for hedonic and motivational signaling in the brain. The medium spiny
      neurons are GABAergic, but they colocalize enkephalin. Purpose of this study was
      to investigate the role of the opioidergic mechanisms of the ventral pallidum in
      ethanol self-administration behavior. METHODS: Effects of bilateral
      microinjections of MU-, delta-, and kappa-opioid receptor agonists and
      antagonists into the ventral pallidum on voluntary ethanol consumption were
      monitored in alcohol-preferring Alko Alcohol (AA) rats using the 90-minute
      limited access paradigm. RESULTS: Stimulation of MU-opioid receptors with DAMGO
      (0.01 to 0.1 MUg) or morphine (1 to 10 MUg) in the ventral pallidum decreased
      ethanol intake dose-dependently. Conversely, blocking MU-receptors with CTOP (0.3
      to 3 MUg) increased ethanol intake significantly. Unlike CTOP, DAMGO also
      increased locomotor activity. Consumption of ethanol was not modified
      significantly by a broad-spectrum opioid receptor antagonist naltrexone, by delta
      opioid receptor agonist DPDPE or antagonist naltrindole, or by a kappa-opioid
      receptor agonist U50,488H or antagonist nor-BNI. CONCLUSIONS: The study provides
      evidence for MU- but not delta- or kappa-opioid receptors in the ventral pallidum
      playing a role in the regulation of voluntary ethanol consumption. Furthermore,
      present findings give support to earlier work, suggesting an essential role of
      pallidal opioidergic transmission in drug reward.

PMID- 21895713
TI  - Corticotropin-releasing factor acting on corticotropin-releasing factor receptor
      type 1 is critical for binge alcohol drinking in mice.
AB  - BACKGROUND: The corticotropin-releasing factor (CRF) system has been implicated
      in the regulation of alcohol consumption. However, previous mouse knockout (KO)
      studies using continuous ethanol access have failed to conclusively confirm this.
      Recent studies have shown that CRF receptor type 1 (CRFR1) antagonists attenuate
      alcohol intake in the limited access "drinking in the dark" (DID) model of binge
      drinking. To avoid the potential nonspecific effects of antagonists, in this
      study, we tested alcohol drinking in CRFR1, CRFR2, CRF, and urocortin 1 (Ucn1) KO
      and corresponding wild-type (WT) littermates using the DID paradigm. METHODS: On
      days 1 to 3, the CRFR1, CRFR2, Ucn1, and CRF KO mice and their respective WT
      littermates were provided with 20% ethanol or 10% sucrose for 2 hours with water
      available at all other times. On day 4, access to ethanol or sucrose was
      increased to 4 hours. At the end of each drinking session, the volume of ethanol
      consumed was recorded, and at the conclusion of the last session, blood was also
      collected for blood ethanol concentration (BEC) analysis. RESULTS: CRFR1 KO mice
      had lower alcohol intakes and BECs and higher intakes of sucrose compared with
      WTs. In contrast, CRFR2 KO mice, while having reduced intakes initially, had
      similar alcohol intakes on days 2 to 4 and similar BECs as the WTs. To determine
      the ligand responsible, Ucn1 and CRF KO and WT mice were tested next. While Ucn1
      KOs had similar alcohol intakes and BECs to their WTs, CRF KO mice showed reduced
      alcohol consumption and lower BECs compared with WTs. CONCLUSIONS: Our results
      confirm that CRFR1 plays a key role in binge drinking and identify CRF as the
      ligand critically involved in excessive alcohol consumption.

PMID- 21895716
TI  - Ethanol-induced loss-of-righting response during ethanol withdrawal in male and
      female rats: associations with alterations in Arc labeling.
AB  - BACKGROUND: There is increasing evidence for relevant sex differences in
      responses to ethanol. Several investigations have found differences in expression
      and recovery from ethanol withdrawal (EW) in people and across various animal
      models. We have found that female rats recover more quickly than male rats and
      show differential responses to various behavioral assessments and pharmacological
      challenges during withdrawal. The purpose of this study was to determine whether
      sex differences in EW behaviors extend to the hypnotic effects of acute ethanol
      administration. METHODS: We used a repeated measures design to assess duration
      and latency for loss-of-righting reflex following an acute injection of ethanol
      (4.2 g/kg; 20% w/v) to pair-fed control or ethanol-withdrawn animals at 1 and 3
      days EW in male, female, and ovariectomized female (OVX) rats. We determined
      protein levels of the activity-regulated cytoskeletal protein (Arc), used as a
      marker for synaptic activity in glutamatergic synapses, in the motor cortex and
      prefrontal cortex across these same treatment conditions. RESULTS: Ethanol
      withdrawn animals had a reduced ethanol-induced sleep time compared to controls
      at 1 day EW. Sleep time remained shortened at 3 days EW for males and OVX, but
      not females. Arc protein levels in motor cortex and preoptic nuclei significantly
      increased at 1 day EW across all sex conditions, suggestive of an association
      with the reduced ethanol-induced sleep times during EW. Arc levels increased
      further for males and OVX, but not females, at the 3 days EW time point.
      CONCLUSIONS: These findings add further support to sex differences in effects of
      and responses to ethanol. They suggest that the more rapid recovery from EW for
      females than males also includes expression of tolerance to the hypnotic effects
      of ethanol. These sex differences may involve some differential neuroadaptations
      in glutamatergic signaling.

PMID- 21895715
TI  - An optimized method for the measurement of acetaldehyde by high-performance
      liquid chromatography.
AB  - BACKGROUND: Acetaldehyde is produced during ethanol metabolism predominantly in
      the liver by alcohol dehydrogenase and rapidly eliminated by oxidation to acetate
      via aldehyde dehydrogenase. Assessment of circulating acetaldehyde levels in
      biological matrices is performed by headspace gas chromatography and reverse
      phase high-performance liquid chromatography (RP-HPLC). METHODS: We have
      developed an optimized method for the measurement of acetaldehyde by RP-HPLC in
      hepatoma cell culture medium, blood, and plasma. After sample deproteinization,
      acetaldehyde was derivatized with 2,4-dinitrophenylhydrazine (DNPH). The reaction
      was optimized for pH, amount of derivatization reagent, time, and temperature.
      Extraction methods of the acetaldehyde-hydrazone (AcH-DNP) stable derivative and
      product stability studies were carried out. Acetaldehyde was identified by its
      retention time in comparison with AcH-DNP standard, using a new chromatography
      gradient program, and quantitated based on external reference standards and
      standard addition calibration curves in the presence and absence of ethanol.
      RESULTS: Derivatization of acetaldehyde was performed at pH 4.0 with an 80-fold
      molar excess of DNPH. The reaction was completed in 40 minutes at ambient
      temperature, and the product was stable for 2 days. A clear separation of AcH-DNP
      from DNPH was obtained with a new 11-minute chromatography program. Acetaldehyde
      detection was linear up to 80 MUM. The recovery of acetaldehyde was >88% in
      culture media and >78% in plasma. We quantitatively determined the ethanol
      derived acetaldehyde in hepatoma cells, rat blood and plasma with a detection
      limit around 3 MUM. The accuracy of the method was <9% for intraday and <15% for
      interday measurements, in small volume (70 MUl) plasma sampling. CONCLUSIONS: An
      optimized method for the quantitative determination of acetaldehyde in biological
      systems was developed using derivatization with DNPH, followed by a short RP-HPLC
      separation of AcH-DNP. The method has an extended linear range, is reproducible
      and applicable to small-volume sampling of culture media and biological fluids.

PMID- 21895717
TI  - Acamprosate for alcohol dependence: a sex-specific meta-analysis based on
      individual patient data.
AB  - BACKGROUND: It is unknown whether women derive comparable benefits and have a
      similar safety and tolerability profile as men from acamprosate, a widely
      prescribed drug for the maintenance of abstinence in alcohol dependence. The
      objective of this study was to assess sex-specific differences in the efficacy,
      safety, and tolerability of acamprosate in the treatment of women and men with
      alcohol dependence. METHODS: A sex-specific meta-analysis was conducted based on
      individual patient data (IPD). Data were obtained from double-blind, randomized
      controlled trials with quantitative drinking measures in patients with alcohol
      dependence receiving oral acamprosate or placebo. Sources included PubMed,
      PsychInfo, and Cochrane electronic databases; reference lists from retrieved
      articles and presentations at professional meetings; and direct access to authors
      and companies who provided IPD. RESULTS: Individual records were obtained from
      1,317 women and 4,794 men who participated in 22 eligible studies conducted in 18
      countries. IPD meta-analyses found a significant beneficial effect of acamprosate
      relative to placebo across all 4 efficacy end points: an incremental gain of
      10.4% (95% CI 7.1 to 13.7, p < 0.001) in percentage of abstinent days, an
      incremental gain of 11.0% (7.4 to 14.6, p < 0.001) in percentage of no heavy
      drinking days, an odds ratio of 1.9 (1.6 to 2.2, p < 0.001) for rate of complete
      abstinence, and an odds ratio of 1.9 (1.6 to 2.3, p < 0.001) for rate of no heavy
      drinking, over the study duration. Acamprosate was also associated with
      significantly higher rates of treatment completion (p = 0.004) and medication
      compliance (p < 0.001) than placebo. Men and women did not differ on any measure
      of acamprosate efficacy, safety, or tolerability. CONCLUSIONS: This sex-specific
      IPD meta-analysis provides evidence that acamprosate has a significant effect
      compared with placebo in improving rates of abstinence and no heavy drinking in
      both women and men with alcohol dependence. Further, acamprosate was associated
      with significantly higher rates of treatment completion and medication compliance
      than placebo among both women and men and had a comparable safety and
      tolerability profile.

PMID- 21895718
TI  - Genetic polymorphisms of genes coding to alcohol-metabolizing enzymes in western
      Mexicans: association of CYP2E1*c2/CYP2E1*5B allele with cirrhosis and liver
      function.
AB  - BACKGROUND: Alcoholic cirrhosis constitutes a major public health problem in the
      world where ADH1B, ALDH2, and CYP2E1 polymorphisms could be playing an important
      role. We determined ADH1B*2, ALDH2*2, and CYP2E1*c2 allele frequencies in healthy
      control individuals (C) and patients with alcoholic cirrhosis (AC) from western
      Mexico. METHODS: Ninety C and 41 patients with AC were studied. Genotype and
      allele frequency were determined through polymerase chain reaction-restriction
      fragment length polymorphisms. RESULTS: Polymorphic allele distribution in AC was
      1.6%ADH1B*2, 0.0%ALDH2*2, and 19.5%CYP2E1*c2; in C: 6.1%ADH1B*2, 0%ALDH2*2, and
      10.6%CYP2E1*c2. CYP2E1*c2 polymorphic allele and c1/c2 genotype frequency were
      significantly higher (p < 0.05 and p < 0.01, respectively) in patients with AC
      when compared to C. Patients with AC, carrying the CYP2E1*c2 allele, exhibited
      more decompensated liver functioning evaluated by total bilirubin and prothrombin
      time, than c1 allele carrying patients (p < 0.05). Cirrhosis severity, assessed
      by Child's Pugh score and mortality, was higher in patients carrying the c2
      allele, although not statistically significant. CONCLUSIONS: In this study,
      CYP2E1*c2 allele was associated with susceptibility to AC; meanwhile, ADH1B*2 and
      ALDH2*2 alleles were not. CYP2E1*c2 allele was associated with AC severity, which
      could probably be attributed to the oxidative stress promoted by this polymorphic
      form. Further studies to clearly establish CYP2E1*c2 clinical relevance in the
      development of alcohol-induced liver damage and its usefulness as a probable
      prognostic marker, should be performed. Also, increasing the number of patients
      and including a control group conformed by alcoholic patients free of liver
      damage may render more conclusive results. These findings contribute to the
      understanding of the influence of gene variations in AC development among
      populations, alcohol metabolism, and pharmacogenetics.

PMID- 21895719
TI  - To approach or avoid alcohol? Automatic and self-reported motivational tendencies
      in alcohol dependence.
AB  - BACKGROUND: Motivational conflict is central to alcohol dependence, with patients
      reporting motivation to limit their drinking at the same time as urges to drink
      alcohol. In addition, dual process models of addiction emphasise the power of
      automatic cognitive processes, particularly automatic approach responses elicited
      by alcohol-related cues, as determinants of drinking behavior. We aimed to
      examine the strength of automatic and self-reported alcohol approach and
      avoidance tendencies among alcohol-dependent inpatients relative to matched
      controls. METHODS: A total of 63 alcohol-dependent patients undergoing
      detoxification and 64 light-drinking controls completed a stimulus-response
      compatibility (SRC) task, which assesses the speed of categorization of alcohol
      related pictures by making symbolic approach and avoidance movements. We also
      included modified versions of the SRC task to assess automatic motivational
      conflict, that is, strong approach and avoidance tendencies elicited
      simultaneously by alcohol-related cues. RESULTS: There were no differences
      between alcohol-dependent patients and controls on the SRC task, although
      individual differences in the quantity of alcohol consumed before entering
      treatment were significantly positively correlated with the strength of approach
      (but not avoidance) tendencies elicited by alcohol-related cues. Automatic
      approach tendencies were also positively correlated with self-reported "approach"
      inclinations and negatively correlated with self-reported "avoidance"
      inclinations. CONCLUSIONS: Although alcohol-dependent patients and matched
      controls did not differ on automatic approach and avoidance tendencies elicited
      by alcohol-related cues, individual differences in the quantity of alcohol
      consumed before entering treatment were associated with the strength of automatic
      approach tendencies elicited by alcohol cues.

PMID- 21895720
TI  - Alcohol dehydrogenase-1B Arg47His polymorphism and upper aerodigestive tract
      cancer risk: a meta-analysis including 24,252 subjects.
AB  - BACKGROUND: Cancers of the upper aerodigestive tract (UADT) include malignant
      tumors of the oral cavity, pharynx, larynx, and esophagus, account for
      approximately 4% of all new cancers in world. Alcohol drinking is an established
      risk factor for UADT cancers, and the rate of alcohol metabolism could
      significantly been influenced by genetic polymorphisms of alcohol dehydrogenase
      1B (ADH1B) His47Arg (rs1229984). To evaluate whether combined evidence shows
      ADH1B His47Arg as a common genetic variant that influenced the risk of UADT
      cancers, we considered all available studies in a meta-analysis. METHODS:
      Eighteen studies were combined representing data of 8,539 cases and 15,713
      controls for meta-analysis. Stratified analyses were carried out to determine the
      gene-environment interaction between ADH1B His47Arg and alcohol drinking and gene
      gene interaction between ADH1B His47Arg and aldehyde dehydrogenase-2 (ALDH2)
      Glu/Lys related to UADT cancer risk. Potential sources of heterogeneity between
      studies were explored; sensitivity analysis and publication bias was also
      evaluated. RESULTS: The ADH1B 47Arg allele was found to be associated with
      increased risk of UADT cancers, the pooled odds ratios (ORs) being 1.66 (95% CI:
      1.54 to 1.79) and 3.47 (95% CI: 2.76 to 4.36) for the His/Arg and Arg/Arg
      genotypes compared with the His/His genotype, respectively. An 18.48-fold
      increase in OR (95% CI: 12.95 to 26.40) for UADT cancers among alcohol drinkers
      with Arg/Arg genotype was found, when compared among nondrinkers with the His/His
      genotype. Significant interaction between carriers with ADH1B 47Arg and ALDH2
      487Lys allele related to risk for UADT cancers was more evident, compared with
      noncarriers (OR = 10.31, 95% CI: 5.45 to 18.85). CONCLUSIONS: ADH1B 47Arg allele
      is a common genetic variant that increased the risk of UADT cancers; furthermore,
      it modulates the susceptibility to UADT cancers coupled with alcohol drinking and
      interaction with the ALDH2 487Lys allele.

PMID- 21895721
TI  - GABA(A) receptor modulation during adolescence alters adult ethanol intake and
      preference in rats.
AB  - BACKGROUND: To address the hypothesis that GABA(A) receptor modulation during
      adolescence may alter the abuse liability of ethanol during adulthood, the
      effects of adolescent administration of both a positive and negative GABA(A)
      receptor modulator on adult alcohol intake and preference were assessed. METHODS:
      Three groups of adolescent male rats received 12 injections of lorazepam (3.2
      mg/kg), dehydroepiandrosterone (DHEA, 56 mg/kg), or vehicle on alternate days
      starting on postnatal day (PD) 35. After this time, the doses were increased to
      5.6 and 100 mg/kg, respectively, for 3 more injections on alternate days.
      Subjects had access to 25 to 30 g of food daily, during the period of the first 6
      injections, and 18 to 20 g thereafter. Food intake of each group was measured 60
      minutes after food presentation, which occurred immediately after drug
      administration on injection days or at the same time of day on noninjection days.
      When subjects reached adulthood (PD 88), ethanol preference was determined on 2
      separate occasions, an initial 3-day period and a 12-day period, in which
      increasing concentrations of ethanol were presented. During each preference test,
      intake of water, saccharin, and an ethanol/saccharin solution was measured after
      each 23-hour access period. RESULTS: During adolescence, lorazepam increased 60
      minute food intake, and this effect was enhanced under the more restrictive
      feeding schedule. DHEA had the opposite effect on injection days, decreasing food
      intake compared with noninjection days. In adulthood, the lorazepam-treated group
      preferred the 2 lowest concentrations of ethanol/saccharin more than saccharin
      alone compared with vehicle-treated subjects, which showed no preference for any
      concentration of ethanol/saccharin over saccharin. DHEA-treated subjects showed
      no preference among the 3 solutions. CONCLUSIONS: These data demonstrate that
      GABA(A) receptor modulation during adolescence can alter intake and preference
      for ethanol in adulthood and highlights the importance of drug history as an
      important variable in the liability for alcohol abuse.

PMID- 21895722
TI  - The effects of age at drinking onset and stressful life events on alcohol use in
      adulthood: a replication and extension using a population-based twin sample.
AB  - BACKGROUND: A study by Dawson and colleagues (Alcohol Clin Exp Res 2007; 31:69)
      using data from National Epidemiologic Survey on Alcohol and Related Condition
      found earlier drinking onset age, and higher levels of past-year stressful life
      events (SLE) were associated with higher past-year alcohol consumption. The aims
      of our study were as follows: (i) to attempt to replicate this interaction; (ii)
      to extend it by examining sex and event dependence as potential moderators of the
      effect; and (iii) to estimate the roles of genetic and environmental factors in
      mediating the overlap of early drinking onset and SLE in their relations with
      alcohol consumption. METHODS: Data were from 1,382 female and 2,218 male drinkers
      interviewed as part of the Virginia Adult Twin Study of Psychiatric and Substance
      Use Disorders. Regression models were used to evaluate the main and interactive
      effects of early drinking onset and moderate or severe past-year SLE on past-year
      drinking density (PYDD), a weighted quantity-frequency measure of alcohol
      consumption. Analyses adjusted for demographic covariates and were stratified by
      sex and whether SLE were independent or dependent on the person's actions, as
      rated by interviewers. Structural twin models were used to estimate the degree to
      which early drinking onset, SLE, and their interaction accounted for additive
      genetic, common environmental and individual-specific variance in PYDD. RESULTS:
      We replicated the prior finding of a main effect of higher alcohol consumption
      among individuals reporting earlier drinking onset. Age at drinking onset
      accounted for about 5% of the variation in PYDD, and this association was mostly
      attributable to overlapping genetic influences. Evidence for an interaction
      between onset age and SLE was generally weak, possibly because of lower power and
      other methodological differences from Dawson and colleagues' study. However,
      there was some evidence consistent with an interaction of higher PYDD among early
      drinking men who experienced independent SLE and early drinking women with
      dependent SLE. CONCLUSIONS: We confirmed prior findings of an association between
      early age at drinking onset with higher past-year drinking among young- and
      middle-aged adults and found limited evidence supporting a replication for higher
      stress-related drinking among early-onset drinkers. The association is consistent
      with early onset and stress-related drinking being attributable to overlapping
      genetic liability. Among early drinkers, our results suggest sex differences in
      consumption with regard to event dependence.

PMID- 21895723
TI  - The role of the Asn40Asp polymorphism of the mu opioid receptor gene (OPRM1) on
      alcoholism etiology and treatment: a critical review.
AB  - The endogenous opioid system has been implicated in the pathophysiology of
      alcoholism as it modulates the neurobehavioral effects of alcohol. A variant in
      the mu opioid receptor gene (OPRM1), the Asn40Asp polymorphism, has received
      attention as a functional variant that may influence a host of behavioral
      phenotypes for alcoholism as well as clinical response to opioid antagonists.
      This paper will review converging lines of evidence on the effect of the Asn40Asp
      SNP on alcoholism phenotypes, including: (i) genetic association studies; (ii)
      behavioral studies of alcoholism; (iii) neuroimaging studies; (iv)
      pharmacogenetic studies and clinical trials; and (v) preclinical animal studies.
      Together, these lines of research seek to elucidate the effects of this
      functional polymorphism on alcoholism etiology and treatment response.

PMID- 21895725
TI  - Atrial fibrillation hospitalization is not increased with short-term elevations
      in exposure to fine particulate air pollution.
AB  - BACKGROUND: Previous studies have observed that short-term exposure to elevated
      concentrations of particulate matter (PM) air pollution increases risk of acute
      ischemic heart disease events and heart failure hospitalization, alters cardiac
      autonomic function, and increases risk of arrhythmias. This study explored the
      potential associations between short-term elevations in PM exposure and atrial
      fibrillation (AF). METHODS AND RESULTS: A case-crossover study design was used to
      explore associations between fine PM (PM2.5, particles with an aerodynamic
      diameter <=2.5 MUm) and 10,457 AF hospitalizations from 1993 to 2008 of patients
      who lived on Utah's Wasatch Front. Patients were hospitalized at Intermountain
      Healthcare facilities with a primary diagnosis of AF. Concurrent day exposure and
      cumulative lagged exposures for up to 21 days were explored and the data were
      stratified by sex, age, and previous or subsequent admission for myocardial
      infarction. Although the estimated associations between PM2.5 and AF
      hospitalizations for the various lag structures and strata were consistently
      positive suggestive of risk, they were not statistically significant and they
      were extremely small compared to previously observed associations with ischemic
      heart disease events and heart failure hospitalizations. Further, we observed no
      additive risk between PM2.5 and AF hospitalization in those with respiratory
      disease or sleep apnea. CONCLUSIONS: Unlike previously observed associations with
      ischemic heart disease events and heart failure hospitalizations using similar
      study design and approaches, this study found that hospitalization for AF was not
      significantly associated with elevations in short-term exposure to fine PM air
      pollution.

PMID- 21895724
TI  - A dual mechanism for I(Ks) current reduction by the pathogenic mutation KCNQ1
      S277L.
AB  - BACKGROUND: The hereditary long QT syndrome is characterized by prolonged
      ventricular repolarization that can be caused by mutations to the KCNQ1 gene,
      which encodes the alpha subunits of the cardiac potassium channel complex that
      carries the I(Ks) current (the beta subunits are encoded by KCNE1). In this
      study, we characterized a deleterious variant, KCNQ1-S277L, found in a patient
      who presented with sudden cardiac death in the presence of cocaine use. METHODS:
      The KCNQ1-S277L mutation was analyzed via whole-cell patch clamp, confocal
      imaging, surface biotinylation assays, and computer modeling. RESULTS: Homomeric
      mutant KCNQ1-S277L channels were unable to carry current, either alone or with
      KCNE1. When co-expressed in a 50/50 ratio with WT KCNQ1, current density was
      reduced in a dominant-negative manner, with the residual current predominantly
      wild type. There was no change in the activation rate and minimal changes to
      voltage-dependent activation for both KCNQ1 current and I(Ks) current.
      Immunofluorescence confocal imaging revealed reduced surface expression of mutant
      KCNQ1-S277L, which was biochemically confirmed by surface biotinylation showing a
      44% decrease in mutant surface expression. Expression of KCNQ1-S277L with human
      ether-a-go-go-related gene (HERG) did not significantly affect HERG protein or
      current density compared to KCNQ1-WT co-expression. CONCLUSION: The KCNQ1-S277L
      mutation causes biophysical defects that result in dominant-negative reduction in
      KCNQ1 and I(Ks) current density, and a trafficking defect that results in reduced
      surface expression, both without affecting HERG/I(Kr) . KCNQ1-S277L mutation in
      the proband resulted in defective channels that compromised repolarization
      reserve, thereby enhancing the arrhythmic susceptibility to pharmacological
      blockage of I(Kr) current.

PMID- 21895726
TI  - Left ventricular pacing in right ventricular cardiomyopathy: blessing or blunder?
AB  - Arrhythmogenic right ventricular dysplasia (ARVD) predominantly involves the
      right ventricle, and myocardium is progressively replaced by fat and fibrous
      tissue in the apex, base, and outflow tract regions. This pathology, and the
      progressive nature of the disease, poses special challenges for implant and
      subsequent appropriate functioning of an implantable cardioverter-defibrillator.
      This case report describes a solution to problems during lead placement in
      patients with ARVD.

PMID- 21895727
TI  - Ranolazine reduces ventricular tachycardia burden and ICD shocks in patients with
      drug-refractory ICD shocks.
AB  - BACKGROUND: There are limited options for patients who present with
      antiarrhythmic-drug (AAD)-refractory ventricular tachycardia (VT) with recurrent
      implantable cardioverter defibrillator (ICD) shocks. Ranolazine is a drug that
      exerts antianginal and antiischemic effects and also acts as an antiarrhythmic in
      isolation and in combination with other class III medications. Ranolazine may be
      an option for recurrent AAD-refractory ICD shocks secondary to VT, but its
      efficacy, outcomes, and tolerance are unknown. METHODS AND RESULTS: Twelve
      patients (age 65 +/- 9.7 years) were treated with ranolazine. Eleven (92%) were
      male, and 10 (83%) had ischemic heart disease with an average ejection fraction
      of 0.34 +/- 0.13. All patients were on a class III AAD (11 amiodarone, one
      sotalol), with six (50%) receiving mexilitene or lidocaine. Five patients had a
      prior ablation and two were referred for a VT ablation at the index presentation.
      The QRS increased nonsignificantly from 128 +/- 31 ms to 133 +/- 31 ms, and the
      QTc increased nonsignificantly from 486 +/- 32 ms to 495 +/- 31 ms after
      ranolazine initiation. Over a follow-up of 6 +/- 6 months, 11 (92%) patients had
      a significant reduction in VT and no ICD shocks were observed. VT ablation was
      not required in those referred. In two patients, gastrointestinal side effects
      limited long-term use. Of these two patients, one died due to progressive heart
      failure. In one patient, severe hypoglycemia limited dosing to 500 mg daily, but
      this was sufficient for VT control. CONCLUSION: Ranolazine proved effective in
      reducing VT burden and ICD shocks in patients with AAD-refractory VT. Ranolazine
      should be further tested for this indication and considered for clinical
      application when other options have proven ineffective.

PMID- 21895728
TI  - Radiofrequency catheter ablation of posterior paraseptal accessory pathway with
      atresia of the coronary sinus ostium.
AB  - A 42-year-old man was referred to our hospital for an electrophysiologic study
      because of recurrent episodes of palpitation. On coronary angiogram, an anomalous
      atresia of the coronary sinus (CS) ostium was discovered. The ablation catheter
      was inserted from the right femoral artery to the accessory pathway (AP) of
      posterior paraseptal area. The earliest retrograde atrial activation was recorded
      in the 5-6 o'clock region of the mitral annulus. Radiofrequency energy was
      delivered to this site, resulting in elimination of the AP. After this
      application, there was persistent ventriculoatrial dissociation and led to
      successful ablation of the AP.

PMID- 21895729
TI  - Antiviral activity of Distictella elongata (Vahl) Urb. (Bignoniaceae), a
      potentially useful source of anti-dengue drugs from the state of Minas Gerais,
      Brazil.
AB  - AIMS: To investigate the in vitro antiviral activity of Distictella elongata
      (Vahl) Urb. ethanol extracts from leaves (LEE), fruits (FEE), stems and their
      main components. METHODS AND RESULTS: The antiviral activity was evaluated
      against human herpesvirus type 1 (HSV-1), murine encephalomyocarditis virus
      (EMCV), vaccinia virus Western Reserve (VACV-WR) and dengue virus 2 (DENV-2) by
      the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)
      colorimetric assay. LEE presented anti-HSV-1 [EC(50) 142.8 +/- 5.3 MUg ml(-1);
      selectivity index (SI) 2.0] and anti-DENV-2 activity (EC(50) 9.8 +/- 1.3 MUg ml(
      1) ; SI 1.5). The pectolinarin (1) isolated from LEE was less active against HSV
      1 and DENV-2. A mixture of the triterpenoids ursolic, pomolic and oleanolic acids
      was also obtained. Ursolic and oleanolic acids have shown antiviral activity
      against HSV-1. A mixture of pectolinarin (1) and acacetin-7-O-rutinoside (2) was
      isolated from FEE and has presented anti-DENV-2 activity (EC(50) 11.1 +/- 1.6 MUg
      ml(-1) ; SI > 45). Besides the antiviral activity, D. elongata has disclosed
      antioxidant effect. CONCLUSIONS: These data shows that D. elongata has antiviral
      activity mainly against HSV-1 and DENV-2, besides antioxidant activity. These
      effects might be principally attributed to flavonoids isolated. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Distictella elongata might be considered a promising source
      of anti-dengue fever phytochemicals.

PMID- 21895730
TI  - Comparison of disc diffusion, Etest and agar dilution for susceptibility testing
      of colistin against Enterobacteriaceae.
AB  - AIMS: In this study, we compared different methods of colistin susceptibility
      testing, disc diffusion, agar dilution and Etest using a set of
      Enterobacteriaceae isolates that included colistin-resistant strains. METHODS AND
      RESULTS: Susceptibility of 200 clinical isolates of Enterobacteriaceae to
      colistin was tested to compare agar dilution (reference method), disc diffusion
      (50 and 10 MUg) and Etest. MICs (minimum inhibitory concentrations) were
      interpreted using the criteria established by the European Committee on
      Antimicrobial Susceptibility Testing (EUCAST). Colistin exhibited excellent
      activity against Escherichia coli and E. cloacae (MIC90 = 0.5 mg l(-1)). In
      contrast, colistin was less active against Klebsiella pneumoniae (MIC90 = 16 mg
      l(-1)). Resistance rates varied from 0% in E. coli to 1.8% in E. cloacae and 13%
      in K. pneumoniae. High rates of very major errors were observed in the disc
      diffusion test using either the criteria of the Comite de l'antibiogramme de la
      Societe Francaise de Microbiologie (CA-SFM) or the criteria of the Clinical and
      Laboratory Standards Institute (CLSI), respectively, 3.5 and 2.5%. When the
      criteria of Gales et al. were applied, the number of very major errors was
      reduced to one (0.5%). The Etest showed good concordance with agar dilution
      method. CONCLUSION: Disc susceptibility testing methods are unreliable on
      detecting colistin resistance. MIC should be determined to confirm the
      susceptibility results by disc diffusion. SIGNIFICANCE AND IMPACT OF THE STUDY:
      We recommend the determination of MIC by Etest for all multidrug-resistant
      Enterobacteriaceae when colistin is required for the treatment.

PMID- 21895731
TI  - Relapse of health related quality of life and psychological health in patients
      with chronic obstructive pulmonary disease 6 months after rehabilitation.
AB  - AIMS: This study aimed to evaluate the short- and long-term effects of 4-week
      inpatient rehabilitation on health-related quality of life (HRQL), anxiety and
      depression in patients with chronic obstructive pulmonary disease (COPD) and
      investigate the influence of clinical and socio-demographical factors on
      unaltered or improved HRQL after discharge. METHODS: A total of 111 consecutive
      cases with mild-to-very severe COPD were recruited from three rehabilitation
      centres and measured at baseline (t1), 4 weeks (t2) and 6-month follow-up (t3).
      Disease severity was assessed by spirometric tests, HRQL by The St. George's
      Respiratory Questionnaire (SGRQ) and anxiety and depression by The Hospital
      Anxiety and Depression Scale (HADS). Socio-demography and co-morbidity was also
      reported. Changes in SGRQ and HADS scores from baseline to follow-up were
      analysed by paired-sample t-test, and logistic regression was used to investigate
      the influence of different factors on HRQL after discharge. RESULTS: Health
      related quality of life and depression improved between t1 and t2: a change of 
      3.6 for the SGRQ impact score (p = 0.009), -2.8 for the SGRQ total score (p =
      0.012), a clinical relevant change of -4.0 for the SGRQ symptom score (p = 0.012)
      and a reduction of -0.7 for the HADS depression score (p = 0.011). Between t2 and
      t3, all SGRQ and HADS scores deteriorated with enhancement of SGRQ impact score
      (+3.5, p = 0.016), SGRQ total score (+2.5, p = 0.029), HADS anxiety score (+1.1,
      p = 0.000), HADS depression score (+0.6, p = 0.022) and HADS total score (+1.7, p
      = 0.000). No significant differences between t1 and t3 were found, except for
      HADS anxiety score (+0.9, p = 0.003). Patients living alone were 2.9 times more
      likely to maintain or improve HRQL 6 months after rehabilitation than patients
      living with someone (95% CI 1.1-7.8, p = 0.039). CONCLUSION: Short-term benefits
      on HRQL and depression after rehabilitation relapsed at 6-month follow-up, but
      without any further deterioration from baseline. Living alone may be beneficial
      to maintain or improve HRQL after discharge.

PMID- 21895732
TI  - A prospective evaluation of postural stimulation testing, computed tomography and
      adrenal vein sampling in the differential diagnosis of primary aldosteronism.
AB  - CONTEXT: In primary aldosteronism (PA), discriminating unilateral from bilateral
      disease is crucial because adrenalectomy is frequently curative in the former
      case but rarely helps in the latter. Various series have reported the utility of
      postural stimulation testing (PST), cross-sectional imaging and adrenal vein
      sampling (AVS) in the assessment of PA, but most of these studies were
      retrospective. OBJECTIVE: To prospectively determine the diagnostic utility of
      PST, AVS and computed tomography (CT) using a radiological scoring system in the
      assessment of PA in a tertiary centre, as well as to document the incidence of
      autonomous cortisol cosecretion. DESIGN AND SETTING: Fifty consecutive patients
      with PA underwent PST, CT, AVS and a low-dose dexamethasone suppression test with
      measurement of serum cortisol at 48 h. For patients who underwent surgery,
      histological confirmation, and a normal postoperative serum aldosterone
      concentration and plasma renin activity were taken as evidence for unilateral
      disease. For other patients, results from successful adrenal vein sampling were
      the diagnostic evidence against which CT and PST were assessed. RESULTS: Postural
      stimulation testing had a sensitivity and specificity of 44-56% and 71-75%,
      respectively. CT had an overall sensitivity and specificity of 77% and 80%,
      respectively, rising to 100% sensitivity and specificity if there was a single,
      discrete macronodule with an unequivocally normal contralateral gland. Evidence
      of cosecretion of cortisol occurred in 14% of patients. CONCLUSIONS: Preliminary
      experience is presented of an objective radiological scoring system for selecting
      patients with PA for AVS. PST provides little, if any, useful additional
      information. A significant minority of patients with PA exhibit evidence of
      cortisol cosecretion, which may have implications for perioperative management.

PMID- 21895733
TI  - Chemerin levels are positively correlated with abdominal visceral fat
      accumulation.
AB  - OBJECTIVE: Chemerin, a recently discovered adipocytokine, may be linked to
      obesity and obesity-associated metabolic complications. However, the relationship
      between visceral fat accumulation and chemerin is still unknown. Therefore, we
      investigated the relationship between serum chemerin levels and body composition
      as measured by computed tomography (CT). PATIENTS: We recruited 173 men and women
      without histories of diabetes or cardiovascular disease. MEASUREMENTS: Biomarkers
      of metabolic risk factors and body composition by computed tomography were
      assessed. Serum chemerin levels were measured by enzyme-linked immunosorbent
      assay. RESULTS: Chemerin levels correlated with body mass index (BMI), waist
      circumference, abdominal visceral fat area, blood pressure, fasting insulin,
      homoeostasis model of assessment-insulin resistance, total cholesterol,
      triglyceride, creatinine, aspartate aminotransferase and alanine
      aminotransferase. By stepwise multiple regression analysis, abdominal visceral
      fat area, blood pressure and total cholesterol levels independently affected
      chemerin levels. CONCLUSIONS: Abdominal visceral fat accumulation, blood pressure
      and lipid profile were significantly associated with serum chemerin levels. Our
      findings suggest that chemerin may be a mediator that links visceral obesity to
      cardiovascular risk factors.

PMID- 21895734
TI  - Cognitive vulnerability and the aetiology and maintenance of dental anxiety.
AB  - OBJECTIVES: Dental anxiety prevalence has not changed markedly in the last 30
      years, in spite of more modern and less painful technology. The objective of this
      study was to explore the four components (dangerousness, uncontrollability,
      unpredictability and disgustingness) of the Cognitive Vulnerability Model (CVM)
      in relation to the acquisition and maintenance of dental anxiety/phobia. METHODS:
      Three hundred and seventy-five participants were recruited through two dental
      anxiety online support groups. They completed an online questionnaire which
      included: a formal dental anxiety measure; open-ended questions regarding the
      perceived origins of their dental anxiety, and questions specifically assessing
      the CVM components in the acquisition and maintenance of their fear. RESULTS:
      Perceptions of the dental context as uncontrollable and unpredictable were
      considered important in fear acquisition, however 'dangerousness' was not as
      fully established and 'disgustingness' was not considered salient by
      participants. Three of the key components of the CVM (controllability,
      dangerousness and disgustingness) predicted current dental anxiety scores
      explaining 54% of the variance. Unpredictability was not found to have a
      significant independent relationship with dental anxiety. CONCLUSIONS: These
      findings show general support for the CVM as an explanatory model for maintaining
      dental anxiety, though its role as a model for fear acquisition is still not
      fully established.

PMID- 21895735
TI  - Dental service utilization by Europeans aged 50 plus.
AB  - OBJECTIVES: To describe variations in the utilization of dental services by
      persons aged 50+ from 14 European countries and to identify the extent to which
      such variations are attributable to differences in oral health need and in
      accessibility of dental care. METHODS: We use data from the Survey of Health,
      Ageing, and Retirement in Europe (SHARE Waves 2 and 3) and estimate a series of
      multivariate logistic regression models to analyze variations in dental service
      utilization (overall dental attendance, preventive treatment and/or operative
      treatment, dental attendance in early life years) RESULTS: Overall dental
      attendance and incidence of solely preventive treatment are comparatively high in
      the Netherlands, Sweden, Denmark, Germany, and Switzerland. In contrast, overall
      dental attendance is relatively low in Spain, Italy, France, Greece, Poland, and
      Ireland. Moreover, a high incidence of solely operative treatment is observed in
      Austria, Italy, and France, whereas in the Netherlands, Sweden, Denmark,
      Switzerland, and Ireland, the incidence of solely operative treatment is
      comparably low. By and large, these variations persist even when controlling for
      cross-country differences in oral health need and in accessibility of dental
      care. CONCLUSIONS: In comparison with other European regions, there is a tendency
      toward more frequent and preventive dental treatment of the elderly populations
      residing in Scandinavia and Western Europe. Such utilization patterns appear only
      partially attributable to differences in need for and accessibility of dental
      care.

PMID- 21895736
TI  - GAPDH: a common enzyme with uncommon functions.
AB  - Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has long been recognized as an
      important enzyme for energy metabolism and the production of ATP and pyruvate
      through anaerobic glycolysis in the cytoplasm. Recent studies have shown that
      GAPDH has multiple functions independent of its role in energy metabolism.
      Although increased GAPDH gene expression and enzymatic function is associated
      with cell proliferation and tumourigenesis, conditions such as oxidative stress
      impair GAPDH catalytic activity and lead to cellular aging and apoptosis. The
      mechanism(s) underlying the effects of GAPDH on cellular proliferation remains
      unclear, yet much evidence has been accrued that demonstrates a variety of
      interacting partners for GAPDH, including proteins, various RNA species and
      telomeric DNA. The present mini review summarizes recent findings relating to the
      extraglycolytic functions of GAPDH and highlights the significant role this
      enzyme plays in regulating both cell survival and apoptotic death.

PMID- 21895737
TI  - Mitochondrial decay in ageing: 'Qi-invigorating' schisandrin B as a hormetic
      agent for mitigating age-related diseases.
AB  - 1. The mitochondrial free radical theory of ageing (MFRTA) proposes a primary
      role for mitochondrial reactive oxygen species (ROS) in the ageing process. The
      reductive hot spot hypothesis of mammalian ageing serves as a supplement to the
      MFRTA by explaining how the relatively few cells that have lost oxidative
      phosphorylation capacity due to mitochondrial DNA mutations can be toxic to the
      rest of the body and result in the development of age-related diseases. 2.
      Schisandrin B (SchB), which can induce both a glutathione anti-oxidant and a heat
      shock response via redox-sensitive signalling pathways, is a hormetic agent
      potentially useful for increasing the resistance of tissues to oxidative damage.
      The enhanced cellular/mitochondrial anti-oxidant status and heat shock response
      afforded by SchB can preserve the structural and functional integrity of
      mitochondria, suggesting a potential role for SchB in ameliorating age-related
      diseases. 3. Future studies will focus on investigating whether SchB can produce
      the hormetic response in humans.

PMID- 21895738
TI  - Human epicardial fat: what is new and what is missing?
AB  - 1. Putative physiological functions of human epicardial adipose tissue (EAT)
      include: (i) lipid storage for the energy needs of the myocardium; (ii)
      thermoregulation, whereby brown fat components of EAT generate heat by non
      shivering thermogenesis in response to core cooling; (iii) neuroprotection of the
      cardiac autonomic ganglia and nerves; and (iv) regulation of vasomotion and
      luminal size of the coronary arteries. Under pathophysiological circumstances,
      EAT may play an adverse paracrine role in cardiac arrhythmias and in lipotoxic
      cardiomyopathy, but of major current interest is its hypothetical role as an
      immunological organ contributing to inflammation around coronary artery disease
      (CAD). 2. The amount of EAT measured either by echocardiographic thickness over
      the free wall of the right ventricle or as volume by computed tomography expands
      in patients with obesity both without and with CAD. The mechanisms other than
      obesity governing the increase in EAT volume in CAD are unknown, but EAT around
      CAD is infiltrated by chronic inflammatory cells and overexpresses genes for
      adipokines that have pro- or anti-inflammatory actions and regulate oxidative
      stress plus angiogenesis. 3. Many cross-sectional studies have shown positive
      associations between increased EAT mass and stable CAD burden. One prospective
      population-based epidemiological study suggested that EAT volume at baseline is a
      predictor of acute myocardial infarction, but was without significant incremental
      predictive value after adjustment for established cardiovascular risk factors.
      However, strategies are needed to obtain robust epidemiological, interventional
      and experimental evidence to prove or disprove the hypothesis that EAT is a
      cardiovascular risk factor locally contributing to CAD.

PMID- 21895739
TI  - Restoring a sense of wellness following colorectal cancer: a grounded theory.
AB  - AIM:   This paper reports a study to develop a grounded theory to explain the
      experience of recovery following surgery for colorectal cancer. BACKGROUND:  
      Studies have adopted a biomedical framework to measure quality of life and
      symptom distress following surgery for colorectal cancer. These studies suggest
      that symptoms of pain, insomnia and fatigue, may persist for many months
      following treatment. Fewer studies have considered the individual's experiences
      and perspective of the emotional, social and cultural aspects of recovery.
      METHODS:   A longitudinal study using grounded theory was conducted with 12
      individuals, who had received surgery for colorectal cancer. Semi-structured
      interviews were conducted at four time points over 1 year following surgery,
      between 2007 and 2009. Grounded theory analysis was undertaken using Strauss and
      Corbin's framework. FINDINGS:   Recovery is described in three phases: disrupting
      the self; repairing the self; restoring the self. The core category is Restoring
      a sense of wellness; fostered through awareness and enjoyment of the physical,
      emotional, spiritual and social aspects of life. A sense of wellness exists as a
      duality with a sense of illness, where both perspectives may co-exist but one
      usually takes precedence. A sense of illness pervades when the individual is
      preoccupied with illness and the illness continues to disrupt their daily life.
      CONCLUSION:   Recovery takes time and energy, particularly when the individual is
      at home and in relative isolation from health professionals. Opportunities exist
      for nurses to provide information and support to facilitate the individual in
      their progress towards achieving a sense of wellness.

PMID- 21895740
TI  - Using Campinha-Bacote's process of cultural competence model to examine the
      relationship between health literacy and cultural competence.
AB  - AIM: This paper presents a discussion of the relation between health literacy and
      cultural competence in nursing practice. BACKGROUND: Cultural competence involves
      understanding values, beliefs, traditions and customs of diverse groups. Health
      literacy is the degree to which individuals can obtain, process, and understand
      health information to make healthcare decisions. Cultural competence and health
      literacy are directly related to healthcare. Campinha-Bacote's Process of
      Cultural Competence Model can assist nurses in addressing cultural issues
      associated with a person's low health literacy. Data sources.  Literature
      searches were performed using CINAHL, ERIC, Academic Search Premier, Health
      Source Nursing, MasterFILE Premier and Academic OneFile. All articles reviewed
      were published in peer reviewed journals in English from the 1990s to the present
      and were relevant to health literacy and cultural competence in nursing. Books
      and other supporting scholarly sources were also used. Discussion.  Health
      literacy and cultural competence are related. Applying Campinha-Bacote's Process
      of Cultural Competence Model using the mnemonic ASKED (awareness, skills,
      knowledge, encounters and desire) involves incorporating culturally appropriate
      assessments and disseminating healthcare information at lower literacy levels and
      is needed for nurses to provide care for ethnic minorities and diverse
      populations. Implications for nursing.  Health literacy should be assessed and
      care should be based on a client's level of understanding and cultural values and
      norms. CONCLUSION: Nurses can care for ethnic minorities by using resources that
      target health literacy deficits and by increasing their own cultural competence.

PMID- 21895741
TI  - Seasonal changes in the histochemical properties of the olfactory epithelium and
      vomeronasal organ in the Japanese striped snake, Elaphe quadrivirgata.
AB  - Seasonal changes in the histochemical properties of the vomeronasal and olfactory
      epithelia of the Japanese striped snake were examined in four seasons, viz. the
      reproductive, pre-hibernating, hibernating and post-hibernating seasons. In the
      vomeronasal and olfactory supporting cells, secretory granules were much more
      abundant in the hibernating season than in the other seasons. In the vomeronasal
      and olfactory receptor cells, the lipofuscin granules were much fewer in the post
      hibernating season than in the other seasons. In histochemical studies with 21
      lectins, several lectins stained the vomeronasal and olfactory epithelia
      (receptor cells, supporting cells and free border) more weakly in the hibernating
      season than in the reproductive season. However, all lectins stained both
      epithelia in the hibernating season after sialic acid removal in a similar manner
      as in the reproductive season after sialic acid removal. These lectin
      histochemical studies indicate that sialic acid residues in the vomeronasal and
      olfactory epithelia are more numerous in the hibernating season than in the
      reproductive season. The results suggest that during hibernation, the vomeronasal
      and olfactory receptor cells possibly undergo rapid cell turnover, and that
      during this time, the vomeronasal and olfactory epithelia are securely protected
      from pathogens by an innate immune defence system.

PMID- 21895742
TI  - Immunohistochemical aspects of anti-microbial properties in goat submandibular
      glands.
AB  - Salivary glands are known as the principal source of anti-microbial substances,
      which are considered to be essential components of saliva. The distribution of
      anti-microbial substances in the submandibular glands of Japanese miniature
      (Shiba) goat was studied using immunohistochemical methods as performed by
      physical development procedures. In the goat, anti-microbial substances such as
      lysozyme, IgA, lactoferrin and beta-defensin were demonstrated to be
      immunolocalized in the submandibular glands, especially in the serous demilunes
      and duct cells. The results obtained are discussed with regard to the specific
      functions of the saliva. The presence and secretion of anti-microbial substances
      suggest that they participate in the maintenance of oral health among the
      elements of saliva.

PMID- 21895743
TI  - Magnetic resonance imaging of normal nasal cavity and paranasal sinuses in cats.
AB  - A detailed description of the nasal cavity and paranasal sinuses in clinically
      normal cats using magnetic resonance imaging (MRI) is presented. The heads of
      seven normal cats were imaged using a 1.5-T MR unit and two sequences spin echo
      (SE) T1-weighted and fast spin echo (FSE) T2-weighted. Eighteen relevant MR scans
      were taken in the transverse (12 scans) and dorsal (six scans) planes. Anatomical
      structures were identified and labelled using anatomical texts, sectioned
      specimen heads and previous studies. MR scans revealed the soft-tissue structure
      of the head. Identified relevant anatomical structures seen on MRI will assist
      clinicians to better understand MR images and evaluate pathological conditions
      that affect the nasal region.

PMID- 21895744
TI  - Clinical efficacy and safety of tacrolimus ointment in patients with vitiligo.

PMID- 21895745
TI  - Effect of prior vaccination with a seasonal trivalent influenza vaccine on the
      antibody response to the influenza pandemic H1N1 2009 vaccine: a randomized
      controlled trial.
AB  - Vaccination with the non-adjuvanted split-virion A/California/7/2009 influenza
      vaccine (pandemic H1N1 2009 vaccine) began in October 2009 in Japan. The present
      study was designed to assess the effect of prior vaccination with a seasonal
      trivalent influenza vaccine on the antibody response to the pandemic H1N1 2009
      vaccine in healthy adult volunteers. One hundred and seventeen participants aged
      22 to 62 were randomly assigned to two study groups. In Group 1 (the priming
      group), participants were first vaccinated with the seasonal trivalent influenza
      vaccine followed by two separate one-dose vaccinations of the pandemic H1N1 2009
      vaccine, whereas in Group 2 (the non-priming group), the participants were first
      vaccinated with one dose of the pandemic H1N1 2009 vaccine, followed by
      simultaneous vaccination of the seasonal trivalent vaccine and the second dose of
      the pandemic H1N1 2009 vaccine. The participants in Group 2 had a seroprotection
      rate (SPR) of 79.7% and a seroconversion rate (SCR) of 79.7% in the
      hemagglutination-inhibition test after the first dose of the pandemic H1N1 2009
      vaccine, indicating that the pandemic H1N1 2009 vaccine is sufficiently
      immunogenic. On the other hand, the participants of Group 1 had a significantly
      weaker antibody response, with a SPR of 60.8% and a SCR of 58.5%. These results
      indicate that prior vaccination with the seasonal trivalent influenza vaccine
      inhibits the antibody response to the pandemic H1N1 2009 vaccine. Therefore, the
      pandemic H1N1 2009 vaccine should be administered prior to vaccination with the
      seasonal trivalent influenza vaccine.

PMID- 21895746
TI  - Inhibition of hepatitis C virus replication through adenosine monophosphate
      activated protein kinase-dependent and -independent pathways.
AB  - Persistent infection with hepatitis C virus (HCV) is closely correlated with type
      2 diabetes. In this study, replication of HCV at different glucose concentrations
      was investigated by using J6/JFH1-derived cell-adapted HCV in Huh-7.5 cells and
      the mechanism of regulation of HCV replication by AMP-activated protein kinase
      (AMPK) as an energy sensor of the cell analyzed. Reducing the glucose
      concentration in the cell culture medium from 4.5 to 1.0 g/L resulted in
      suppression of HCV replication, along with activation of AMPK. Whereas treatment
      of cells with AMPK activator 5-aminoimidazole-4-carboxamide 1-beta-D
      ribofuranoside (AICAR) suppressed HCV replication, compound C, a specific AMPK
      inhibitor, prevented AICAR's effect, suggesting that AICAR suppresses the
      replication of HCV by activating AMPK in Huh-7.5 cells. In contrast, compound C
      induced further suppression of HCV replication when the cells were cultured in
      low glucose concentrations or with metformin. These results suggest that low
      glucose concentrations and metformin have anti-HCV effects independently of AMPK
      activation.

PMID- 21895747
TI  - Differential effect of prior influenza infection on alveolar macrophage
      phagocytosis of Staphylococcus aureus and Escherichia coli: involvement of
      interferon-gamma production.
AB  - The influenza A virus is one of the main causes of respiratory infection.
      Although influenza virus infection alone can result in pneumonia, secondary
      bacterial infection combined with the virus is the major cause of morbidity and
      mortality. Interestingly, while influenza infection increases susceptibility to
      some bacteria, including Streptococcus pneumoniae, Staphylococcus aureus (S.
      aureus), and Haemophilus influenzae, other bacteria such as Escherichia coli (E.
      coli) and Klebsiella pneumoniae are not associated with influenza infection. The
      reason for this discrepancy is not known. In this study, it was found that prior
      influenza virus infection inhibits murine alveolar macrophage phagocytosis of S.
      aureus but not of E. coli. Here, the mechanism for this inhibition is elucidated:
      prior influenza virus infection strongly increases interferon gamma (IFN-gamma)
      production. Furthermore, it was shown that IFN-gamma differentially affects
      alveolar macrophage phagocytosis of S. aureus and E. coli. The findings of the
      present study explain how influenza virus infection increases susceptibility to
      some bacteria, such as S. aureus, but not others, and provides evidence that IFN
      gamma might be a promising target for protecting the human population from
      secondary bacterial infection by influenza.

PMID- 21895748
TI  - Major histocompatibility complex class I-restricted cytotoxic T lymphocyte
      responses during primary simian immunodeficiency virus infection in Burmese
      rhesus macaques.
AB  - Major histocompatibility complex class I (MHC-I)-restricted CD8(+)  cytotoxic T
      lymphocyte (CTL) responses are crucial for the control of human immunodeficiency
      virus (HIV) and simian immunodeficiency virus (SIV) replication. In particular,
      Gag-specific CTL responses have been shown to exert strong suppressive pressure
      on HIV/SIV replication. Additionally, association of Vif-specific CTL frequencies
      with in vitro anti-SIV efficacy has been suggested recently. Host MHC-I genotypes
      could affect the immunodominance patterns of these potent CTL responses. Here,
      Gag- and Vif-specific CTL responses during primary SIVmac239 infection were
      examined in three groups of Burmese rhesus macaques, each group having a
      different MHC-I haplotype. The first group of four macaques, which possessed the
      MHC-I haplotype 90-010-Ie, did not show Gag- or Vif-specific CTL responses.
      However, Nef-specific CTL responses were elicited, suggesting that primary SIV
      infection does not induce predominant CTL responses specific for Gag/Vif epitopes
      restricted by 90-010-Ie-derived MHC-I molecules. In contrast, Gag- and Vif
      specific CTL responses were induced in the second group of two 89-075-Iw-positive
      animals and the third group of two 91-010-Is-positive animals. Considering the
      potential of prophylactic vaccination to affect CTL immunodominance post-viral
      exposure, these groups of macaques would be useful for evaluation of vaccine
      antigen-specific CTL efficacy against SIV infection.

PMID- 21895749
TI  - Safety and immunogenicity of BPV-1 L1 virus-like particles in a dose-escalation
      vaccination trial in horses.
AB  - REASONS FOR PERFORMING STUDY: Infection with bovine papillomaviruses types 1 and
      2 (BPV-1, BPV-2) can lead to the development of therapy-resistant skin tumours
      termed sarcoids and possibly other skin diseases in equids. Although sarcoids
      seriously compromise the welfare of affected animals and cause considerable
      economic losses, no prophylactic vaccine is available to prevent this common
      disease. In several animal species and man, immunisation with papillomavirus-like
      particles (VLP) has been shown to protect efficiently from papillomaviral
      infection. HYPOTHESIS: BPV-1 L1 VLPs may constitute a safe and highly immunogenic
      vaccine candidate for protection of horses against BPV-1/-2-induced disease.
      METHODS: Three groups of 4 horses each received 50, 100 or 150 ug of BPV-1 L1
      VLPs, respectively, on Days 0, 28 and 168. Three control horses received adjuvant
      only. Horses were monitored on a daily basis for one week after each immunisation
      and then in 2 week intervals. Sera were collected immediately before, 2 weeks
      after each vaccination and one and 2 years after the final boost and analysed by
      pseudovirion neutralisation assay. RESULTS: None of the horses showed adverse
      reactions upon vaccination apart from mild and transient swelling in 2
      individuals. Irrespective of the VLP dose, all VLP-immunised horses had developed
      a BPV-1-neutralising antibody titre of >= 1600 plaque forming units (pfu)/ml 2
      weeks after the third vaccination. Eight of 10 trial horses still available for
      follow-up had neutralising antibody titres >= 1600 pfu/ml one year and >= 800
      pfu/ml 2 years after the last immunisation. CONCLUSION: Intramuscular BPV-1 L1
      VLP vaccination in horses is safe and results in a long-lasting antibody response
      against BPV-1. Neutralisation titres were induced at levels that correlate with
      protection in experimental animals and man. POTENTIAL RELEVANCE: BPV-1 L1 VLPs
      constitute a promising vaccine candidate for prevention of BPV-1/-2-induced
      disease in equids.

PMID- 21895750
TI  - Digital hypothermia inhibits early lamellar inflammatory signalling in the
      oligofructose laminitis model.
AB  - REASONS FOR PERFORMING STUDY: The pathophysiological events inhibited by
      prophylactic digital hypothermia that result in reduction of the severity of
      acute laminitis are unknown. OBJECTIVES: To determine if digital hypothermia
      inhibits lamellar inflammatory signalling during development of oligofructose
      (OF) induced laminitis. METHODS: Fourteen Standardbred horses were given 10 g/kg
      bwt OF by nasogastric tube with one forelimb (CRYO) continuously cooled by
      immersion in ice and water and one forelimb (NON-RX) at ambient temperature.
      Lamellae were harvested prior to the onset of lameness (24 h post OF
      administration, DEV group, n = 7) or at the onset of lameness (OG1 group, n = 7).
      Lamellar mRNA was purified and cDNA produced for real time-quantitative PCR
      analysis of mRNA concentrations of cytokines (IL-6, IL-1beta, IL-10), chemokines
      (CXCL1, CXCL6, CXCL8/IL-8, MCP-1, MCP-2), cell adhesion molecules (ICAM-1, E
      selectin), COX-2 and 3 housekeeping genes. Data were analysed (NON-RX vs. CRYO,
      NON-RX vs. archived control [CON, n = 7] lamellar tissue) using nonparametric
      tests. RESULTS: Compared with CON, the OG1 NON-RX had increased (P<0.05) lamellar
      mRNA concentrations of all measured mediators except IL-10, IL-1beta and MCP-1/2,
      whereas only CXCL8 was increased (P<0.05) in DEV NON-RX. Within the OG1 group,
      CRYO limbs (compared with NON-RX) had decreased (P<0.05) mRNA concentrations of
      the majority of measured inflammatory mediators (no change in MCP-1 and IL-10).
      Within the DEV group, mRNA concentrations of CXCL-1, ICAM-1, IL-1beta, CXCL8 and
      MCP-2 were decreased (P<0.05) and the anti-inflammatory cytokine IL-10 was
      increased (compared with NON-RX limbs; P<0.05). CONCLUSIONS: Digital hypothermia
      effectively blocked early lamellar inflammatory events likely to play an
      important role in lamellar injury including the expression of chemokines,
      proinflammatory cytokines, COX-2 and endothelial adhesion molecules. POTENTIAL
      RELEVANCE: This study demonstrates a potential mechanism by which hypothermia
      reduces the severity of acute laminitis, and may help identify molecular targets
      for future laminitis intervention.

PMID- 21895751
TI  - Magnetic resonance imaging findings in the carpus and proximal metacarpal region
      of 50 lame horses.
AB  - REASONS FOR PERFORMING STUDY: There is limited information on magnetic resonance
      imaging (MRI) findings in the carpus and proximal metacarpal region of lame
      horses. OBJECTIVES: To document MRI findings in horses with lameness localised to
      the carpus and/or proximal metacarpal region. METHODS: Clinical records of horses
      that underwent MRI of the carpus and/or proximal metacarpal region at the Animal
      Health Trust between January 2003 and September 2010 were reviewed. Magnetic
      resonance images of all horses and available radiographs, ultrasonographic and
      scintigraphic images were assessed. When possible, MRI findings were related to
      the results of other diagnostic imaging techniques. RESULTS: Seventy-two MR
      studies of 58 lame limbs in 50 horses from a broad range of work disciplines and
      ages were reviewed. The most commonly detected primary abnormality was decreased
      signal intensity in T1- and T2-weighted images in the medial aspect of the carpal
      bones and/or the proximomedial aspect of the metacarpal bones (n = 29). Nine
      horses had syndesmopathy between the second and third metacarpal bones. In 6
      horses the primary abnormalities were identified in the palmar cortex of the
      third metacarpal bone (McIII). Significant abnormalities of the suspensory
      ligament (SL) with associated lesions in the adjacent palmar cortex of the McIII
      were seen in 4 limbs. Ligament and associated osseous abnormalities between the
      second and third carpal bones and second and third metacarpal bones were detected
      in 4 limbs. CONCLUSIONS AND POTENTIAL RELEVANCE: Magnetic resonance imaging
      enabled diagnosis of a variety of lesions not detected by conventional imaging in
      horses from a wide range of work disciplines. The distribution of injury types
      differed considerably from previous studies.

PMID- 21895752
TI  - Osteochondrosis and osteochondral fragments in Standardbred trotters: prevalence
      and relationships.
AB  - REASONS FOR PERFORMING STUDY: Developmental orthopaedic diseases (DOD) such as
      osteochondrosis (OC)/osteochondrosis dissecans (OCD), palmar/plantar
      osteochondral fragments (POF), ununited palmar/plantar eminences (UPE) and
      dorsoproximal first phalanx fragments are well recognised in the horse.
      Aetiopathogeneses are controversial and molecular genetic screening of DNA has
      recently been employed for their elucidation. Precise phenotypic definition and
      knowledge of breed-specific prevalence and interrelations are essential for the
      interpretation of following genomic studies in Standardbred trotters. OBJECTIVES:
      To assess the prevalence, trend of development and interrelation of DOD in
      tarsocrural, metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints in
      Standardbred trotters. METHODS: The tarsocrural and MCP/MTP joints of 464
      Norwegian Standardbred yearlings were radiographed and the prevalence and
      interrelation of osteochondral lesions calculated. RESULTS: Osteochondral lesions
      were diagnosed in 50.7% of the horses. The prevalence of tarsocrural OC/OCD at
      the distal intermediate ridge of the tibia (DIT) and the lateral trochlear ridge
      of the talus (LTT) was 19.3%. The prevalence of OC/OCD in MCP joints was 3.6%,
      whereas those of POF and UPE in MCP/MTP joints were 23.1 and 3.9%, respectively.
      Interrelation was evident for 1) most equivalent lesions in joint homologues, 2)
      OCD DIT and OCD LTT and 3) POF and UPE. Lesions in hock and fetlock joints were
      generally not significantly associated. CONCLUSIONS: The prevalence of
      tarsocrural OC/OCD in Norwegian Standardbreds is apparently increasing, whereas
      that of other articular DOD appears stable. Association analyses verify
      bilateralism for most equivalent lesions and suggest aetiological resemblance
      also between other lesions. The absence of a significant association between
      tarsocrural OCD and POF implies that the lesions must be considered statistically
      different disorders. POTENTIAL RELEVANCE: The prevalence results emphasise that
      DOD should be considered in Standardbred breeding regimens (e.g. by sire
      selection subsequent to progeny testing). Also, improved phenotypic definitions
      will help elucidate the true causal genes in following genomic studies.

PMID- 21895753
TI  - Effects of acute exercise on angiotensin I-converting enzyme (ACE) activity in
      horses.
AB  - Angiotensin I-converting enzyme (ACE) level measurement in blood samples is an
      important tool in human medicine for the detection, treatment and control of
      diseases such as sarcoidosis and hypertension. Recently ACE has been advocated as
      being correlated to athletic aptitude in human athletes and a genetic
      polymorphism has been shown to be responsible for the enzymatic levels in the
      circulation. The objective of this research was to evaluate the effects of acute
      exercise in horses in order to increase the understanding of a possible
      correlation between ACE levels in plasma and performance in equine athletes. A
      standardised exercise test (SET) to fatigue was conducted on 8 horses and
      repeated venous blood collections carried out for ACE activity measurements
      before, during and after the SET. Our results show an increase in ACE activity up
      to fatigue and a return to baseline values at 30 min post exercise.

PMID- 21895754
TI  - Complications after two transphyseal bridging techniques for treatment of angular
      limb deformities of the distal radius in 568 Thoroughbred yearlings.
AB  - REASONS FOR PERFORMING STUDY: Surgical correction of carpal angular limb
      deformities by growth retardation is commonly undertaken with a screws and
      tension band wire loop technique (S&W) or a single transphyseal screw (STS). This
      study compares complications after S&W and STS bridging in the distal radius of
      Thoroughbred yearlings. OBJECTIVE: To compare the prevalence of complications
      serious enough to require follow-up radiographs following either S&W or STS
      surgery for growth manipulation in the distal radius of Thoroughbred yearlings.
      METHODS: Medical records and radiographs from Thoroughbred yearlings (age range
      261-457 days) treated for carpal angular limb deformities at a single hospital
      over 2 years were reviewed. Each of the techniques was used exclusively during a
      single year. The complication threshold criterion for inclusion was the need for
      nonroutine radiographs of the operated site anytime after implant insertion or
      removal. RESULTS: Of 568 horses, 253 received S&W and 315 received STS. Horses
      were of similar age at the time of surgery for STS and S&W. Single transphyseal
      screws were left in place for a significantly shorter amount of time (16 days).
      Sex, the limb(s) treated and medial vs. lateral placement were not significantly
      different between techniques. Complications included physitis post implant
      removal, metaphyseal collapse post implant removal, infection, overcorrection and
      seroma formation severe enough to require radiography. Physitis and metaphyseal
      collapse occurred significantly more frequently with STS compared with S&W.
      Infection, overcorrection and seromas were not significantly different between
      techniques. CONCLUSION: The STS and S&W techniques are both viable treatment
      options for correction of carpal angular limb deformities. However, horses
      treated with the STS technique have a significantly increased risk of developing
      physitis or metaphyseal collapse. POTENTIAL RELEVANCE: Horses treated with STS
      bridging have a significantly increased risk of developing the post correction
      complications of moderate to severe physitis and metaphyseal collapse compared
      with horses treated with S&W bridging.

PMID- 21895755
TI  - Do early skin care practices alter the risk of atopic dermatitis? A case-control
      study.
AB  - The rise in atopic dermatitis prevalence observed in industrialized countries is
      unexplained. We hypothesized that certain skin care practices early in life may
      increase the risk for developing atopic dermatitis. Our case-control study could
      not identify any one practice that increased the odds of developing atopic
      dermatitis, but it revealed that regular lotion use was very common in infants
      who later develop atopic dermatitis.

PMID- 21895756
TI  - Resource utilization and quality of life associated with congenital ichthyoses.
AB  - We explored resource utilization (ResUtil) and quality of life (QOL) associated
      with congenital ichthyoses (CI). Subjects completed an online survey related to
      clinical severity, demographics, ResUtil, and QOL as measured according to the
      Dermatology Life Quality Index (DLQI). Validated Likert scales were used to
      evaluate severity of hyperkeratosis, erythema, and alopecia. ResUtil was
      determined according to time spent daily treating CI symptoms (TimeTx) and number
      of ichthyosis-related dermatology visits (DermVisits) per year. We used linear
      regression to investigate predictors of a transformed DLQI (sqrtDLQI) and
      logistic regression for ResUtil. Of 235 subjects, 60.2% were female, 83.8% were
      Caucasian, 42.3% had a family history (FamHx) of CI, and the mean age was 28.7
      years (SD 20.3). Predictors for worse QOL were hyperkeratosis severity (beta =
      0.27, p < 0.01), erythema (beta = 0.27, p < 0.01), TimeTx (beta = 0.21, p <
      0.01), ichthyosis type (beta = 0.09, p < 0.01), and age (beta = 0.01, p = 0.02).
      Predictors for DermVisits were hyperkeratosis severity (odds ratio [OR] = 1.38,
      95% confidence limit [CL] = 1.01, 1.87), FamHx (OR = 0.28, 95% CL = 0.09, 0.85),
      age (OR = 0.97, 95% CI = 0.96, 0.99), and alopecia severity (OR = 1.43, 95% CL =
      1.12, 1.82). Predictors for treatment duration were erythema (OR = 1.35, 95% CL =
      1.02, 1.78), age (OR = 0.98, 95% CL = 0.96, 0.99), and DLQI (OR = 1.09, 95% CL =
      1.03, 1.15). Increased hyperkeratosis severity and erythema negatively impact QOL
      in the CI. Furthermore, increased disease severity predicted greater ResUtil,
      whereas increased age and FamHx predicted less ResUtil. Our findings suggest that
      better therapies and increased patient education may improve QOL and decrease
      ResUtil.

PMID- 21895757
TI  - Clonality of Staphylococcus aureus colonization over time in attendees of a camp
      for children with chronic dermatoses.
AB  - Chronic dermatoses are risk factors for Staphylococcus aureus colonization;
      little is known about the significance of transmission between persons with
      chronic dermatoses (CD) and their contacts. We collected nasal, axillary, and
      skin swabs for S. aureus from 50 attendees of a camp for children with CD and
      their families at three time points: start and end of 2005 camp and start of 2006
      camp (times A, B, and C, respectively). Thirty-one persons had CD, including
      epidermolysis bullosa (n = 14), atopic dermatitis (n = 7), ichthyosis (n = 5),
      and psoriasis (n = 5). Methicillin susceptibility and genotype were determined
      for all S. aureus isolates. Seventy-one unique S. aureus isolate from 10 clonal
      complexes (CC) were isolated; 14 (20%) were methicillin-resistant (MRSA). Persons
      with CD were more likely than those without CD to be colonized with S. aureus at
      the start of the 2005 (p = 0.01) and 2006 (p = 0.02) camp or at any time or site
      (p = 0.04) or to be persistently colonized with the same S. aureus CC at the
      start and end of the 2005 camp. Persons with atopic dermatitis had the highest
      burden of S. aureus colonization, whereas MRSA was isolated most frequently from
      attendees with epidermolysis bullosa. Three hospitalizations for skin infections
      were noted in people with CD between the 2005 and 2006 camps, versus three
      hospitalizations in the 6 months before the 2005 camp. Although S. aureus
      colonization was frequent among camp attendees (and in persons with CD in
      particular), it was diverse and variable. Camp attendance did not appear to
      affect infection-related clinical outcomes.

PMID- 21895758
TI  - Budesonide-induced periorificial dermatitis presenting as chalazion and
      blepharitis.
AB  - We report a case of periorificial dermatitis caused by suboptimal inhalation of
      budesonide for asthma. The initial skin lesions presented in the eye
      surroundings, leading to diagnostic difficulties and treatment of presumed
      chalazion and staphylococcal folliculitis. After several months, the patient
      developed perioral papules and pustules and was diagnosed with periorificial
      dermatitis. He was efficiently treated with topical metronidazole and oral
      erythromycin.

PMID- 21895759
TI  - Aleukemic leukemia cutis in a child preceding T-cell acute lymphoblastic
      leukemia.
AB  - An 8-year-old boy presented with a widespread cutaneous eruption featuring
      macules, papules, nodules, and ulcers. The histologic infiltrate showed T
      lymphoblasts, but there was no sign of systemic involvement, so aleukemic
      leukemia cutis was diagnosed. Two months later, he developed leukemia in
      peripheral blood and bone marrow that was characterized as T-cell acute
      lymphoblastic leukemia.

PMID- 21895760
TI  - Clinical effects and outcomes with new P2Y12 inhibitors in ACS.
AB  - Thienopyridines have become the cornerstone of treatment for percutaneous
      coronary intervention although no survival benefit has ever been shown with
      clopidogrel despite increasing loading doses. Newly developed P2Y12 inhibitors
      are more potent, more predictable, and have a faster onset of action than
      clopidogrel, characteristics that make them particularly attractive for high-risk
      percutaneous coronary intervention (PCI). Four new P2Y12 inhibitors have been
      tested each of them having particular individual properties. Prasugrel is an oral
      pro-drug leading to irreversible blockade of the P2Y12 receptor and is approved
      worldwide for ACS PCI. Ticagrelor is a direct-acting and reversible inhibitor of
      the P2Y12 receptor with potentially more pleiotropic effects. Cangrelor is an
      intravenous direct and reversible inhibitor of the P2Y12 receptor providing the
      highest level of inhibition, and elinogrel is an intravenous and oral P2Y12
      antagonist with a direct and reversible action. Both prasugrel and ticagrelor,
      opposed to clopidogrel, have shown that stronger P2Y12 inhibition led
      respectively to significant 19 and 16% relative risk reduction of a similar
      primary end point combining cardiovascular death, non-fatal myocardial
      infarction, or non-fatal stroke. Both drugs showed a significant 0.6% absolute
      excess of TIMI major bleeding not related to CABG surgery. Because in clinical
      trials, patients perceived to be at higher risk of bleeding usually are excluded,
      the risk of major and even fatal bleeding might even be higher in a 'real-world'
      setting, i.e. in the elderly patient with comorbidities. On the other hand, these
      newly developed P2Y12 inhibitors decrease mortality after PCI compared with
      clopidogrel. The risk/benefit ratio is particularly favorable in PCI for patients
      with STEMI.

PMID- 21895761
TI  - Pharmacokinetic basis of the antiplatelet action of prasugrel.
AB  - Prasugrel is the most recent development of thienopyridine-type antiplatelet
      drugs. Like the earlier-generation thienopyridines, i.e. ticlopidine and
      clopidogrel, prasugrel is also an inactive prodrug that requires metabolic
      processing in vivo to generate the active antiplatelet metabolite. The efficacy
      of this bioactivation is the key determinant for the pharmacodynamic potency of
      the compound, i.e. the irreversible blockade of the platelet P2Y12-ADP receptor.
      Prasugrel is rapidly absorbed from the gut. After oral administration of standard
      loading doses of 60 mg, maximum plasma levels of the active metabolite are
      achieved within 1 h, effective, maximum inhibition of platelet aggregation at 1-2
      h. Bioconversion of prasugrel into the active metabolite requires two metabolic
      steps that occur in sequence. The first is the generation of a thiolactone
      intermediate, mainly by carboxyesterases-2 in the intestine, the second the
      cytochrome (CYP)-dependent conversion of the thiolactone into the active
      metabolite. This second step involves several cytochromes, most notably CYP3A4,
      CYP2C19, CYP2B6, and CYP2C9. The enzymatic generation of the active metabolite of
      prasugrel is much more effective than that of clopidogrel where only about 5% of
      oral clopidogrel is transformed into the active compound by two-step CYP
      dependent procedures. About 70% of prasugrel metabolites are excreted in the
      urine and 30% in the feces. The molar potency of the respective active
      metabolites of prasugrel and clopidogrel is identical. Thus, the more rapid
      onset, higher potency and lower interindividual variability of antiplatelet
      effects of prasugrel as compared to clopidogrel in vivo are entirely because of
      its more efficient pharmacokinetics.

PMID- 21895763
TI  - Patterns of prescription drug use and incidence of drug-drug interactions in
      patients reporting to medical emergency.
AB  - Pharmaco-epidemiological studies detailing prescribing patterns of physicians are
      very few from developing countries. The present study describes the patterns of
      prescription of drugs by physicians working in different clinical settings in
      India and explores using the prescriptions the incidence of potential drug-drug
      interactions (DDI). This study was a cross-sectional observational study. The
      prescriptions of patients for any chronic medical condition and drug therapy
      received at the first point of contact with health care services for present
      medical emergency were analyzed for information. The prescriptions were also
      analyzed for potential DDI. Data were expressed as mean +/- SD or median and
      inter-quartile range. Multiple logistic regression was used for variables likely
      to be associated with incidence of DDI. Of total 710 patients, 565 prescriptions
      were available for analysis. Of the chronic diseases, hypertension (17.7%) and
      diabetes mellitus (16.8%) were the commonest. Alcoholic liver disease had maximum
      average number of drugs prescribed (3.9). Supplements were the most commonly
      prescribed pharmacological agents for chronic disease (142/796). Patients in 35
      50 years of age consumed maximum average number of drugs (1.9). Antibiotics were
      the most frequently prescribed agents (148/1240) followed by supplements
      (122/1240). We noted 296 mild and moderate potential DDI. Literacy of patients
      and polypharmacy were the factors associated significantly with DDI. Patients in
      India do not consume large number of allopathic medicines. The practice of
      prescribing supplements and antibiotics needs to be reviewed. Potential DDI are
      not an important problem. Prescription policies need significant revision.

PMID- 21895762
TI  - Opioid-like antinociceptive effects of oral administration of a lectin purified
      from the seeds of Canavalia brasiliensis.
AB  - The objective of this study was to evaluate the antinociceptive effects of a
      lectin from Canavalia brasiliensis (ConBr) when administered orally to murine
      models of chemical and thermal nociception. ConBr up to 100 mg/kg produced
      significant and dose-dependent antinociceptive effects: 81% reduction in
      abdominal writhing induced by 0.6% acetic acid; 26 and 52% reduction in early-
      and late-stage paw licking, respectively, induced by 2.5% formalin; and 155%
      increase in reaction latency (heightened thermal pain threshold). In all models,
      the antinociceptive effect was reversed by the lectin-binding carbohydrate alpha
      d-methyl-mannoside and by the nonselective opioid antagonist naloxone. The
      antinociceptive effect observed in the formalin test was inhibited by the delta
      selective antagonist naltrindole and the kappa-selective antagonist nor
      binaltorphimine but not by the MU-selective antagonist cyprodime. In conclusion,
      when administered orally to Swiss mice, the ConBr lectin displayed
      antinociceptive activity, both peripheral and central, mediated by the opioid
      system and involving delta-and kappa-receptors and the lectin domain.

PMID- 21895764
TI  - Neonatal morbidity in singleton late preterm infants compared with full-term
      infants.
AB  - AIM: The aim of this study was to test the hypothesis that singleton late preterm
      infants (34 0/7 to 36 6/7 weeks of gestation) compared with full-term infants
      have a higher incidence of short-term morbidity and stay longer in hospital.
      METHODS: In this retrospective, multicentre study, electronic data of children
      born at five hospitals in Switzerland were recorded. Short-term outcome of late
      preterm infants was compared with a control group of full-term infants (39 0/7 to
      40 6/7 weeks of gestation). Multiple gestations, pregnancies complicated by
      foetal malformations, maternal consumption of illicit drugs and infants with
      incomplete documentation were excluded. The results were corrected for gender
      imbalance. RESULTS: Data from 530 late preterm and 1686 full-term infants were
      analysed. Compared with full-term infants, late preterm infants had a significant
      higher morbidity: respiratory distress (34.7% vs. 4.6%), hyperbilirubinaemia
      (47.7% vs. 3.4%), hypoglycaemia (14.3% vs. 0.6%), hypothermia (2.5% vs. 0.6%) and
      duration of hospitalization (mean, 9.9 days vs. 5.2 days). The risk to develop at
      least one complication was 7.6 (95% CI: 6.2-9.6) times higher among late preterm
      infants (70.8%) than among full-term infants (9.3%). CONCLUSION: Singleton late
      preterm infants show considerably higher rate of medical complications and
      prolonged hospital stay compared with matched full-term infants and therefore
      need more medical and financial resources.

PMID- 21895766
TI  - Exercise deficit disorder in youth: a hidden truth.

PMID- 21895767
TI  - Characterisation of Cl- transporter and channels in experimentally induced myopic
      chick eyes.
AB  - BACKGROUND: Experimental evidence has shown that myopic and hyperopic optical
      defocus induces thickening and thinning of the choroids, respectively, moving the
      retina forward and backward toward the plane of focus; however, the underlying
      mechanism of this phenomenon remains elusive. It has been hypothesised that the
      change in choroidal thickness might be elicited by the alteration of ion and
      fluid transport across the retinal pigment epithelium (RPE). Therefore, the aims
      of the present study were to determine the content of specific Cl(-)
      transporter/channel mRNA and proteins in chick RPE in a normal, untreated state
      and in lens-induced myopia. METHODS: Thirty-five White Leghorn chicks were used.
      Lens-induced myopia was achieved by securing a -10 D lens in one eye, while the
      control eye was mounted with a plano lens. The mRNA and protein expression of the
      targeted Cl(-) transporter and channels were assessed by real-time polymerase
      chain reaction and western blot, respectively. RESULTS: Our results showed that
      the gene and protein products of several Cl(-) transporter and channels including
      NKCC, CFTR, ClC-2, ClC-5, ClC-7 and CLCA were expressed in young chick RPE. After
      one day of -10 D lens wear, in addition to the myopic shift in refraction and
      choroidal thinning, there was a parallel reduction in content of some mRNAs and
      proteins (for example, NKCC) in the myopic eye compared with the fellow eye.
      Spontaneous recovery of these mRNAs and proteins to control levels was
      demonstrated after four days of treatment. CONCLUSION: The relative reduction of
      Cl(-) transporter and channel expression in the myopic eye might cause a decrease
      in ion and fluid transport across the RPE, leading to a thinning of the choroid
      and potentially accelerating axial elongation. Understanding of the identity of
      the Cl(-) transport machinery used in developing lens-induced myopia might
      facilitate development of novel approaches for controlling myopic progression by
      influencing fluid transport by the RPE.

PMID- 21895768
TI  - Toric orthokeratology for high myopic and astigmatic subjects for myopic control.

PMID- 21895769
TI  - Ballistic impact resistance of selected organic ophthalmic lenses.
AB  - PURPOSE: The aim was to assess the impact resistance of coated and uncoated mid
      index spectacle lens materials using the ballistic impact test. METHODS:
      Nominally plano lenses of each material in three thicknesses were obtained. The
      lenses were flat edged to a 50 mm diameter. Each lens was impacted by a 6.35 mm
      steel ball. Impact velocities were selected using the Zippy Estimation by
      Sequential Testing protocol to determine the threshold fracture impact velocity.
      RESULTS: Threshold fracture impact velocity generally increased with thickness;
      however, there was a wide variation in performance among the various lens
      materials at each thickness. In all but two instances, the differences in impact
      velocity at each thickness of lens material were significant. Comparison of the
      data for CR39 and Hoya Phoenix with the results of earlier studies showed that
      the lens mounting is a significant factor. The fracture velocities found in the
      present study were significantly lower than the fracture velocities found when
      the lens edge is restrained in the mounting. A scratch resistant coating reduced
      the impact resistance of CR39. The effect of the antireflection coating on the
      fracture velocity depended on the nature of the base scratch-resistant coating.
      CONCLUSIONS: Mid-index lens materials of the same thickness show widely varying
      levels of impact resistance under the ballistic test. Impact resistance increases
      non-linearly with centre thickness. The lens mounting might affect the results of
      the ballistic impact test. The presence of 'cushion coatings' might enhance
      impact resistance.

PMID- 21895770
TI  - Unrecognized high brachial artery bifurcation is associated with higher rate of
      dialysis access failure.
AB  - A thorough consideration of all factors contributing to successful dialysis
      access creation is necessary to achieve optimal outcomes. A high bifurcation of
      the brachial artery (brachioradial variant) occurs in greater than 20% of
      patients. Dialysis access was created in 22 limbs with this variant--15 fistula,
      and 7 prosthetic grafts. Nonmaturation occurred in 33% of fistula. Early
      thromboses occurred in 29% of prosthetic bridge grafts. In this experience, the
      brachioradial variant is associated with a relatively higher rate of fistula
      nonmaturation and prosthetic graft thromboses. These findings reinforce the
      critical role of preoperative imaging studies in dialysis access creation. A
      sound algorithm for the surgical management of the brachioradial variation
      facilitates decision making and will improve dialysis access outcomes.

PMID- 21895771
TI  - A vascular access coordinator improves the prevalent fistula rate.
AB  - The Centers for Medicare and Medicaid Services set the prevalent arteriovenous
      fistula (AVF) rate of 66% as a national standard. To test the hypothesis that the
      use of a clinical vascular access coordinator could increase the rate of AVF in a
      large Nephrology group practice, we implemented an aggressive, multidisciplinary
      vascular access improvement program led by a trained vascular access coordinator
      (VAC). In early 2009, we established protocols, approved by all physicians, for
      the care of vascular access and implemented by a nurse VAC. We retrospectively
      reviewed Network vascular access data reports from January 2008 through December
      2010. The data show that after the implementation of a comprehensive access
      program led by a VAC, the prevalent AVF rate increased from 50% to 65%. The
      number of grafts decreased while the percentage of dialysis catheters used for
      more than 90 days was cut in half. These data suggest that despite an unchanged
      catheter rate at dialysis initiation, the use of a VAC implementing an
      aggressive, multidisciplinary access program can significantly increase the AVF
      rate while decreasing grafts and prevalent catheter use.

PMID- 21895772
TI  - Transradial percutaneous coronary interventions using sheathless guiding
      catheters: a multicenter registry.
AB  - BACKGROUND: Transradial approach (TRA) for percutaneous coronary interventions
      (PCIs) is a common alternative to transfemoral approach associated with lower
      complications. However, a limitation of TRA is the use of large caliber guiding
      catheters due to the small size of the radial artery. The sheathless guiding
      catheter system that is in diameter 1-2 French (Fr) smaller than the
      corresponding introducer sheath may overcome these difficulties. METHODS: From
      January 2010 through December 2010 in 5 Italian high-volume hospitals, 213
      consecutive patients who underwent TRA-PCIs using the sheathless Eaucath guiding
      catheter system because of small radial artery caliber (Group 1) or undergoing
      bifurcation PCIs (Group 2) were enrolled in this registry. In patients of Group 1
      (n = 79), a 6.5-Fr sheathless guiding catheter was employed, whereas in patients
      of Group 2 (n = 134) a 7.5 Fr was used. RESULTS: Among the 213 patients enrolled,
      270 vessels were treated for 316 lesions. No procedures required conversion to a
      conventional guiding catheter system. There were significantly more female
      patients in Group 1, and they were, older, shorter, and thinner than patients in
      Group 2. No cases of major vascular complications were observed in either groups.
      During procedures, adjunctive devices employed included intravascular ultrasound,
      thrombectomy catheters, and distal protection systems. CONCLUSIONS: The use of
      the sheathless guiding catheter system is feasible for TRA-PCIs in case of small
      radial artery caliber or intended coronary bifurcation intervention.

PMID- 21895773
TI  - The CDKN2A p.A148T variant is associated with cutaneous melanoma in Southern
      Brazil.
AB  - Several germline mutations and sequence variants in cancer predisposition genes
      have been described. Among these, the CDKN2A p.A148T variant appears to be
      frequent in patients with melanoma, at least in certain ethnic groups. In this
      case-control study, we evaluated 127 patients with cutaneous melanoma and 128
      controls from Southern Brazil, the region with the highest melanoma incidence
      rates in the country. Using PCR-RFLP, we demonstrate that CDKN2A p.A148T variant
      was significantly more frequent in patients with melanoma than in controls (12.6%
      vs 3.9%; P=0.009). There was no association between presence of the polymorphism
      and tumor thickness, site of the primary tumor, melanoma subtype, age at
      diagnosis, quantitative and qualitative number of nevi. Patients with a positive
      family of history for other cancers were particularly prone to carry the CDKN2A
      p.A148T allele. All patients with p.A148T-positive melanoma reported European
      ancestry, especially German, and this was confirmed using a panel of ancestry
      informative INDELs. Our data suggest that CDKN2A p.A148T is a melanoma
      susceptibility allele in Southern Brazil and is particularly common in patients
      with melanoma of predominantly European ancestry.

PMID- 21895774
TI  - Inducible nitric oxide synthase (iNOS) and alpha-melanocyte-stimulating hormones
      of iNOS origin play important roles in the allergic reactions of atopic
      dermatitis in mice.
AB  - To elucidate the possible involvement of nitric oxide (NO) derived from inducible
      NO synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we
      used an animal model of atopic dermatitis (AD) induced by epicutaneous
      sensitization and analysed the differences in ear thickness, the frequency of
      scratching and plasma levels of ovalbumin-specific immunoglobulin E (OVA-IgE),
      transforming growth factor (TGF)-beta, tumor necrosis factor (TNF)-alpha,
      adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone
      (alpha-MSH) between control and iNOS(-/-)  mice. Eight-week-old control and iNOS(
      /-)  male C57BL/6j mice were sensitized three times with OVA antigen. Before and
      after the last skin sensitization, the number of scratching incidents and the
      thickness of the ear were examined, and the plasma levels of OVA-IgE, alpha-MSH,
      ACTH, TGF-beta and TNF-alpha were analysed by ELISA. Sensitization of mice with
      OVA resulted in increased plasma levels of OVA-IgE, alpha-MSH, ACTH, TGF-beta and
      TNF-alpha in control, but not in iNOS(-/-)  mice. The administration of l-nitro
      arginine-methyl ester (l-NAME) abolished all the above changes that occurred in
      the control mice. In addition, iNOS(-/-)  mice given alpha-MSH exhibited a change
      similar to that seen in the control, whereas iNOS(-/-)  mice given ACTH, TGF-beta
      or TNF-alpha did not demonstrate any changes. These results indicate that
      symptoms of AD such as scratching can be exacerbated by alpha-MSH, which is
      induced by iNOS-derived NO.

PMID- 21895775
TI  - Infective endocarditis due to Aspergillus following kidney transplantation.

PMID- 21895776
TI  - A rare case of an intra-abdominal flat desmoid tumor causing ureteral
      obstruction.

PMID- 21895777
TI  - Eruptive nevi following bone marrow transplantation: a reflectance confocal
      microscopy study.

PMID- 21895778
TI  - Evaluations of the nutritional value of Jatropha curcas protein isolate in common
      carp (Cyprinus carpio L.).
AB  - Jatropha curcas seeds are rich in oil and protein. The oil is used for biodiesel
      production. Jatropha seed cake (JSC) obtained after oil extraction is rich in
      protein; however, it is toxic (phorbol esters content 1.3 mg/g) and consists of
      50-60% shells, which are indigestible. The principle of isoelectric precipitation
      was used to obtain Jatropha protein isolate (JPI) from JSC and it was detoxified
      (DJPI). Carp (n = 45, 20.3 +/- 0.13 g) were randomly distributed into five groups
      with three replicates and for 12-week fed iso-nitrogenous diets (crude protein
      38%): Control [fishmeal (FM)-based protein]; J(50)  and J(75)  (50% and 75% of FM
      protein replaced by DJPI); S(50)  and S(75)  (50% and 75% of FM protein replaced
      by soy protein isolate). Growth performance and nutrient utilisation parameters
      were highest in S(75)  group and not significantly different to those in J(50) 
      and S(50)  groups but were significantly higher than those for all other groups.
      Similar trend was observed for protein and energy digestibilities of experimental
      diets, whereas opposite trend was observed for the feed to gain ratio. Activities
      of intestinal digestive enzymes did not different significantly between the five
      groups. In conclusion, DJPI is a good quality protein source for carp.

PMID- 21895779
TI  - Concentrations of retinol, 3,4-didehydroretinol, and retinyl esters in plasma of
      free-ranging birds of prey.
AB  - This study investigated vitamin A compounds in the plasma of healthy free-ranging
      Central European raptors with different feeding strategies. Plasma samples of
      nestlings of white-tailed sea eagle [white-tailed sea eagle (WTSE), Haliaeetus
      albicilla) (n = 32), osprey (Pandion haliaetus) (n = 39), northern goshawk
      (Accipiter gentilis) (n = 25), common buzzard (Buteo buteo) (n = 31), and honey
      buzzard (Pernis apivorus) (n = 18) and adults of WTSE (n = 10), osprey (n = 31),
      and northern goshawk (n = 45) were investigated with reversed-phase-high
      performance liquid chromatography (RP-HPLC). In WTSE, northern goshawks and
      common buzzards retinol were the main plasma component of vitamin A, whilst in
      ospreys and honey buzzards, 3,4-didehydroretinol predominated. The median of the
      retinol plasma concentration in the nestlings group ranged from 0.12 to 3.80 MUm
      and in the adult group from 0.15 to 6.13 MUm. Median plasma concentrations of 3,4
      didehydroretinol in nestlings ranged from 0.06 to 3.55 MUm. In adults, northern
      goshawks had the lowest plasma concentration of 3,4-didehydroretinol followed by
      WTSE and ospreys. The plasma of all investigated species contained retinyl esters
      (palmitate, oleate, and stearate). The results show considerable species-specific
      differences in the vitamin A plasma concentrations that might be caused by
      different nutrition strategies.

PMID- 21895780
TI  - Propionate absorbed from the colon acts as gluconeogenic substrate in a strict
      carnivore, the domestic cat (Felis catus).
AB  - In six normal-weight and six obese cats, the metabolic effect of propionate
      absorbed from the colon was assessed. Two colonic infusions were tested in a
      crossover design with intervals of 4 weeks. The test solution contained 4 mmol
      sodium propionate per kg ideal body weight in a 0.2% NaCl solution. Normal saline
      was given as control solution. Solutions were infused into the hindgut over 30
      min. Blood samples were obtained prior to and at various time points after
      starting the infusion. As body condition did not affect evaluated parameters, all
      data were pooled. Plasma glucose concentrations showed differences neither over
      time nor during or after infusion with propionate or control. Plasma amino acid
      concentrations rose over time (p < 0.001), but were similar for both infusions.
      Plasma propionylcarnitine rose markedly towards the end of the propionate
      infusion and decreased afterwards (p < 0.001), whereas 3-hydroxy-3
      methylglutarylcarnitine was lower 30 (p = 0.005) and 60 min (p = 0.032) after
      ending propionate infusions and acetylcarnitine tended to fall at the same time
      points (p = 0.079; p = 0.080), suggesting inhibition of gluconeogenesis from
      pyruvate and amino acids, but initiation of propionate-induced gluconeogenesis.
      In conclusion, propionate absorbed from the colon is hypothesized to act as
      gluconeogenic substrate, regardless of the cat's body condition.

PMID- 21895781
TI  - The effect of excess cobalt on milk fatty acid profiles and transcriptional
      regulation of SCD, FASN, DGAT1 and DGAT2 in the mammary gland of lactating dairy
      cows.
AB  - The main objective of this study was to investigate the effect of excess cobalt
      (Co) on gene expression of stearoyl-CoA desaturase (SCD), fatty acid synthase
      (FASN), diacylglycerol acyltransferase 1 (DGAT1) and diacylglycerol
      acyltransferase 2 (DGAT2) of lactating dairy cows in relation to milk fatty acid
      profile. Seven multiparous cows of the Norwegian Red cattle breed (NRF) had their
      basal diet supplemented with 1.4 g Co as a 24 g/l solution of Co-acetate per os
      twice daily for 7 days followed by a 9-day depuration period. Udder biopsies were
      performed prior to the treatment period, after 1 week of treatment and
      immediately after the depuration period. Excess Co reduced the proportion of all
      cis-9 monounsaturated fatty acids and increased the proportion of 18:0 in milk.
      However, gene expression levels of SCD, DGAT1, DGAT2 and FASN were not
      significantly altered. Our results indicate that the effect of Co on milk fatty
      acid profile is mediated at the post-transcriptional level by reduced activity of
      SCD in the mammary gland. Potential mechanisms explaining how Co might reduce
      stearoyl-CoA desaturation are discussed.

PMID- 21895782
TI  - Inhibition of the pro-inflammatory NF-kappaB pathway by a grape seed and grape
      marc meal extract in intestinal epithelial cells.
AB  - In pigs and other monogastric animal, the weaning phase is commonly accompanied
      by an increased susceptibility to gut disorders such as diarrhoea owing to the
      induction of an inflammatory process in the intestine during weaning. Given the
      unfavourable effects of intestinal inflammation on feed consumption, digestive
      capacity of the intestine and growth of animals, controlling intestinal
      inflammation is a reasonable approach for the maintenance of performance
      characteristics of livestock animals. Therefore, this study aimed to study the
      anti-inflammatory potential of a commercial polyphenol-rich grape seed (GS) and
      grape marc (GM) meal-based feed additive in a well-established in vitro
      intestinal epithelium model (polarized Caco-2 cells). The anti-inflammatory
      potential was evaluated by studying the effect of an ethanolic extract obtained
      from the GS and GM meal-based feed additive (GSGME) on the pro-inflammatory
      transcription factor NF-kappaB, which is considered to play a key role in the
      induction of weaning-associated intestinal inflammation. The highest non
      cytotoxic concentrations of the ethanolic GSGME dose dependently reduced TNFalpha
      induced NF-kappaB transactivation and decreased TNFalpha-induced mRNA levels of
      the NF-kappaB target genes IL-1beta, IL-8, MCP-1 and CXCL1 in Caco-2 intestinal
      cells (p < 0.05). No effect of the ethanolic GSGME was observed on the
      cytoprotective Nrf2 pathway in Caco-2 cells as evidenced by an unaltered Nrf2
      transactivation and unchanged mRNA levels of Nrf2 target genes, such as GPX-2,
      NQO1, CYP1A1 and UGT1A1. In conclusion, this study shows that an ethanolic GSGME
      exerts anti-inflammatory effects in intestinal cells under in vitro conditions.
      Thus, polyphenol-rich GSGM meal-based feed additives may be useful for the
      inhibition or prevention of inflammatory processes in the intestine of livestock
      animals, in particular during states with inappropriate NF-kappaB activation in
      the intestinal tissue, such as the weaning phase. Future studies are warranted to
      prove the in vivo anti-inflammatory potential of GSGM meal-based feed additives.

PMID- 21895783
TI  - Energy intake for maintenance in a mammal with a low basal metabolism, the giant
      anteater (Myrmecophaga tridactyla).
AB  - Giant anteaters (Myrmecophaga tridactyla) are among those mammals for which a
      particularly low metabolism has been reported. In order to verify presumably low
      requirements for energy, we used eight anteaters (two males, six females; aged 1
      14 years; body mass between 46 and 64 kg) in a total of 64 individual trials, in
      which a variety of intake levels was achieved on various diets. Digestible energy
      (DE) intake was quantified by measuring food intake and faecal excretion and
      analysing representative samples for gross energy, and animals were weighed
      regularly. Maintenance DE requirements were calculated by regression analysis for
      the DE intake that corresponded to zero weight change. Differences between
      individuals were significant. Older anteaters (n = 3 animals aged 12-15 years in
      29 trials) had lower relative requirements than younger ones (n = 5 animals aged
      1-7 years in 35 trials); thus, giant anteaters resemble other mammals in which
      similar age-specific differences in energy requirements are known. However,
      estimated maintenance requirements were 347 kJ DE/kg(0.75)/day in the anteaters,
      which is low compared to the 460-580 kJ DE/kg(0.75)/day maintenance requirements
      of domestic dogs. The lack of knowledge that metabolic requirements are below the
      mammalian average could make species particularly susceptible to overfeeding, if
      amounts considered adequate for average mammals were provided. Non-scientific
      reports on comparatively fast growth rates and high body masses in captive giant
      anteaters as compared to free-ranging animals suggest that body mass development
      and feeding regimes in captivity should be further assessed.

PMID- 21895784
TI  - Influence of feeding Tinospora cordifolia peripartum on lactation parameters in
      crossbred cows.
AB  - For studying the effect of dietary supplementation of guduchi (Tinospora
      cordifolia) peripartum on lactation an investigation was conducted on 15 pregnant
      Karan Fries crossbred cows which were divided into two groups: treatment group of
      eight cows which were supplemented with guduchi at 60 g/day for 45 days prepartum
      and 120 g/day for 45 days postpartum; control group of seven pregnant cows which
      were not supplemented with guduchi. Jugular blood samples were collected from all
      cows during the periparturient period for analysis of various blood cell and
      plasma parameters. A significantly higher total leukocyte count, lymphocyte
      count, neutrophil count and neutrophil/lymphocyte ratio was recorded in the
      guduchi supplemented treatment group in comparison to untreated control cows
      throughout the experimental period. The increase of milk production over 305 days
      of lactation due to guduchi supplementation was significant (p < 0.05). A
      significant (p < 0.05) reduction in somatic cell count was also observed during
      the experimental period. Milk composition (fat, protein, lactose and SNF) was
      similar (p > 0.05) for both the groups. Plasma non esterified fatty acid (NEFA)
      concentrations were significantly higher (p < 0.01) in cows supplemented with
      guduchi throughout the course of study. Plasma concentration of growth hormone in
      the treated cows was also significantly higher beginning on the day of
      parturition up to 3 weeks postpartum (p < 0.05) in comparison to unsupplemented
      group.

PMID- 21895785
TI  - Comparison of real-time florescence quantitative PCR measurements of VAD1 mRNA
      with three conventional methods in diagnosis and follow-up treatment of
      Cryptococcus neoformans infection.
AB  - This study was to develop a real-time florescence quantitative PCR (RT-FQ-PCR)
      assay to measure virulence-associated DEAD-box RNA helicase (VAD1) mRNA from
      Cryptococcus neoformans and evaluate its potential use in diagnosis and follow-up
      treatment of C. neoformans meningitis (CNM). Cryptococcus neoformans was detected
      using RT-FQ-PCR, ink staining, fungal culturing and C. neoformans antigen
      detection in CNM compared with a normal control. VAD1 mRNA was measured in both
      acute and stable CNM patients. The sensitivity of RT-FQ-PCR (96%) is higher than
      ink staining (72%) and culture culturing (64%) (P<0.05, P<0.05 respectively), but
      its sensitivity is the same as antigen detection (96%, P>0.05). The levels of
      VAD1 mRNA in the acute and stable phase of a C. neoformans infection are 3.042+/
      0.906 and 2.187+/-0.665 respectively (P<0.01). The levels of VAD1 mRNA are
      correlated to the numbers of C. neoformans, intracranial pressure and glucose
      concentration in cerebrospinal fluid (CSF; P<0.01, P<0.01 and P<0.05
      respectively). The levels of expression of VAD1 mRNA in the group of patients who
      received an AmB/5-FC/FZC drug regimen decreased more than in patients taking a 5
      FC/AmB or 5-FC/FCZ drug combination. Quantitative measurements of VAD1 mRNA are
      valuable and reliable in diagnosing C. neoformans infection and evaluating a
      therapy response.

PMID- 21895786
TI  - Use of Dermasilk briefs in recurrent vulvovaginal candidosis: safety and
      effectiveness.
AB  - Despite the generally excellent results achieved with fluconazole 150 mg weekly
      in recurrent vulvovaginal candidosis (RVVC), some patients with a long history of
      disease do not achieve complete resolution of symptoms following antimycotic
      treatment. It is thought that use of tight synthetic fabric underwear could be a
      significant factor in causing recurrence. We decided to compare underwear made of
      Dermasilk(r), a pure fibroin fabric impregnated with a permanent antimicrobial
      protection, with a cotton placebo to see whether it could be a useful adjunctive
      tool in the management of RVVC. We recruited 96 women who had a long-term history
      of RVVC and had not responded to oral antimycotics with complete satisfaction.
      The patients were randomly divided into two groups and instructed to use either
      white cotton placebo briefs or Dermasilk(r) briefs. Both groups were treated with
      fluconazole 150 mg once weekly for 6 months. After 6 months, the Dermasilk group
      showed a statistically significant greater decrease of itching, burning, erythema
      and a smaller number of recurrences than the cotton group. Our work suggests that
      Dermasilk(r) briefs could be a useful adjunctive tool in addition to antimycotic
      treatment to help relieve the discomfort of recurrent vulvovaginitis.

PMID- 21895787
TI  - Species assignment and antifungal susceptibilities of black aspergilli recovered
      from otomycosis cases in Iran.
AB  - Black aspergilli are among the main causative agents of otomycosis worldwide. In
      this study, the species assignment of black aspergilli isolated from otomycosis
      cases in Iran was carried out using sequence analysis of part of the calmodulin
      gene. The results indicate that Aspergillus niger is not the only black
      Aspergillus species involved in otomycosis cases in Iran: Aspergillus awamori and
      Aspergillus tubingensis are also able to cause ear infections. Antifungal
      susceptibility tests were carried out against five antifungal drugs including
      amphotericin B, fluconazole, itraconazole, ketoconazole and terbinafine. All
      isolates were highly susceptible to terbinafine, while they exhibited moderate
      susceptibilities against amphotericin B, fluconazole and ketoconazole.
      Aspergillus niger and A. awamori were found to have higher minimal inhibitory
      concentrations for azoles than A. tubingensis, in accordance with previous
      findings.

PMID- 21895788
TI  - The importomer peroxins are differentially required for peroxisome assembly and
      meiotic development in Podospora anserina: insights into a new peroxisome import
      pathway.
AB  - Peroxisome biogenesis relies on two known peroxisome matrix protein import
      pathways that are mediated by the receptors PEX5 and PEX7. These pathways
      converge at the importomer, a peroxisome-membrane complex that is required for
      protein translocation into peroxisomes and consists of docking and RING-finger
      subcomplexes. In the fungus Podospora anserina, the RING-finger peroxins are
      crucial for meiocyte formation, while PEX5, PEX7 or the docking peroxin PEX14 are
      not. Here we show that PEX14 and the PEX14-related protein PEX14/17 are
      differentially involved in peroxisome import during development. PEX14/17
      activity does not compensate for loss of PEX14 function, and elimination of both
      proteins has no effect on meiocyte differentiation. In contrast, the docking
      peroxin PEX13, and the peroxins implicated in peroxisome membrane biogenesis PEX3
      and PEX19, are required for meiocyte formation. Remarkably, the PTS2 coreceptor
      PEX20 is also essential for meiocyte differentiation and this function does not
      require PEX5 or PEX7. This finding suggests that PEX20 can mediate the import
      receptor activity of specific peroxisome matrix proteins. Our results suggest a
      new pathway for peroxisome import, which relies on PEX20 as import receptor and
      which seems critically required for specific developmental processes, like
      meiocyte differentiation in P. anserina.

PMID- 21895789
TI  - Evolution of a new bacterial pathway for 4-nitrotoluene degradation.
AB  - Bacteria that assimilate synthetic nitroarene compounds represent unique
      evolutionary models, as their metabolic pathways are in the process of adaptation
      and optimization for the consumption of these toxic chemicals. We used Acidovorax
      sp. strain JS42, which is capable of growth on nitrobenzene and 2-nitrotoluene,
      in experiments to examine how a nitroarene degradation pathway evolves when its
      host strain is challenged with direct selective pressure to assimilate non-native
      substrates. Although the same enzyme that initiates the degradation of
      nitrobenzene and 2-nitrotoluene also oxidizes 4-nitrotoluene to 4-methylcatechol,
      which is a growth substrate for JS42, the strain is incapable of growth on 4
      nitrotoluene. Using long-term laboratory evolution experiments, we obtained JS42
      mutants that gained the ability to grow on 4-nitrotoluene via a new degradation
      pathway. The underlying basis for this new activity resulted from the
      accumulation of specific mutations in the gene encoding the dioxygenase that
      catalyses the initial oxidation of nitroarene substrates, but at positions distal
      to the active site and previously unknown to affect activity in this or related
      enzymes. We constructed additional mutant dioxygenases to identify the order of
      mutations that led to the improved enzymes. Biochemical analyses revealed a
      defined, step-wise pathway for the evolution of the improved dioxygenases.

PMID- 21895790
TI  - PerC and GrlA independently regulate Ler expression in enteropathogenic
      Escherichia coli.
AB  - Ler, encoded by the locus of enterocyte effacement (LEE) of attaching and
      effacing (A/E) pathogens, induces the expression of LEE genes by counteracting
      the silencing exerted by H-NS. Ler expression is modulated by several global
      regulators, and is activated by GrlA, which is also LEE-encoded. Typical
      enteropathogenic Escherichia coli (EPEC) strains contain the EAF plasmid, which
      carries the perABC locus encoding PerC. The precise role of PerC in EPEC
      virulence gene regulation has remained unclear, mainly because EPEC strains
      lacking the pEAF still express the LEE genes and because PerC is not present in
      other A/E pathogens such as Citrobacter rodentium. Here, we describe that either
      PerC or GrlA can independently activate ler expression and, in consequence, of
      LEE genes depending on the growth conditions. Both PerC and GrlA, with the aid of
      IHF, counteract the repression exerted by H-NS on ler and can also further
      increase its activity. Our results substantiate the role of PerC and GrlA in EPEC
      virulence gene regulation and suggest that these convergent regulatory mechanisms
      may have represented an evolutionary adaptation in EPEC to co-ordinate the
      expression of plasmid- and chromosome-encoded virulence factors needed to
      successfully colonize its intestinal niche.

PMID- 21895791
TI  - Chimeras of Candida albicans Cdr1p and Cdr2p reveal features of pleiotropic drug
      resistance transporter structure and function.
AB  - Members of the pleiotropic drug resistance (PDR) family of ATP binding cassette
      (ABC) transporters consist of two homologous halves, each containing a nucleotide
      binding domain (NBD) and a transmembrane domain (TMD). The PDR transporters
      efflux a variety of hydrophobic xenobiotics and despite the frequent association
      of their overexpression with the multidrug resistance of fungal pathogens, the
      transport mechanism of these transporters is poorly understood. Twenty-eight
      chimeric constructs between Candida albicans Cdr1p (CaCdr1p) and Cdr2p (CaCdr2p),
      two closely related but functionally distinguishable PDR transporters, were
      expressed in Saccharomyces cerevisiae. All chimeras expressed equally well,
      localized properly at the plasma membrane, retained their transport ability, but
      their substrate and inhibitor specificities differed significantly between
      individual constructs. A detailed characterization of these proteins revealed
      structural features that contribute to their substrate specificities and their
      transport mechanism. It appears that most transmembrane spans of CaCdr1p and
      CaCdr2p provide or affect multiple, probably overlapping, substrate and inhibitor
      binding site(s) similar to mammalian ABC transporters. The NBDs, in particular
      NBD1 and/or the ~150 amino acids N-terminal to NBD1, can also modulate the
      substrate specificities of CaCdr1p and CaCdr2p.

PMID- 21895792
TI  - Control of the replication initiator DnaA by an anti-cooperativity factor.
AB  - Proper coordination of DNA replication with cell growth and division is critical
      for production of viable progeny. In bacteria, coordination of DNA replication
      with cell growth is generally achieved by controlling activity of the replication
      initiator DnaA and its access to the chromosomal origin of replication, oriC.
      Here we describe a previously unknown mechanism for regulation of DnaA. YabA, a
      negative regulator of replication initiation in Bacillus subtilis, interacts with
      DnaA and DnaN, the sliding (processivity) clamp of DNA polymerase. We found that
      in vivo, YabA associated with the oriC region in a DnaA-dependent manner and
      limited the amount of DnaA at oriC. In vitro, purified YabA altered binding of
      DnaA to DNA by inhibiting cooperativity. Although previously undescribed,
      proteins that directly inhibit cooperativity may be a common mechanism for
      regulating replication initiation. Conditions that cause release of DnaN from the
      replisome, or overproduction of DnaN, caused decreased association of YabA and
      increased association of DnaA with oriC. This effect of DnaN, either directly or
      indirectly, is likely responsible, in part, for enabling initiation of a new
      round of replication following completion of a previous round.

PMID- 21895794
TI  - Evolution of catabolic pathways and their regulatory systems in synthetic
      nitroaromatic compounds degrading bacteria.
AB  - Evolution of catabolic pathways for the degradation of synthetic nitroaromatic
      compounds is currently ongoing process because these compounds have been in
      nature only for a short time. Bacteria isolated from contaminated areas contain
      pathways for the degradation of nitroaromatic compounds at different stages of
      progression. Therefore, the emergence of pathways for the degradation of such
      chemicals provides a good opportunity to investigate evolutionary processes
      leading to the emergence of new metabolic routes and their regulatory systems. In
      Burkholderia sp. strain DNT the regulatory gene encoding the LysR-type
      transcriptional regulator DntR is placed divergently of the dinitrotoluene (DNT)
      dioxygenase genes. This regulator still recognizes salicylate, an effector of its
      NagR-like ancestor but not DNT. In this issue of Molecular Microbiology, de las
      Heras et al. demonstrate that the DntR does not respond to any metabolic
      intermediates of the DNT catabolic pathway. The results of this study suggest
      that the catabolic pathway for the degradation of DNT has reached to an early
      stage of evolution when novel specificities of the catabolic enzymes have already
      acquired but the cognate regulatory system is still missing. This research
      addresses some fundamental questions about bottlenecks to be solved during
      evolution of new catabolic operons.

PMID- 21895793
TI  - CsrA-FliW interaction governs flagellin homeostasis and a checkpoint on flagellar
      morphogenesis in Bacillus subtilis.
AB  - CsrA is a widely distributed RNA binding protein that regulates translation
      initiation and/or mRNA stability of target transcripts. CsrA activity is
      antagonized by sRNA(s) containing multiple CsrA binding sites in several Gram
      negative bacterial species. Here we discover FliW, the first protein antagonist
      of CsrA activity that constitutes a partner switching mechanism to control
      flagellin synthesis in the Gram-positive organism Bacillus subtilis. Following
      the flagellar assembly checkpoint of hook completion, secretion of flagellin
      (Hag) releases FliW protein from a FliW-Hag complex. FliW then binds to CsrA and
      relieves CsrA-mediated translational repression of hag for flagellin synthesis
      concurrent with filament assembly. Thus, flagellin homeostatically restricts its
      own translation. Homeostatic autoregulation may be a general mechanism to
      precisely control structural subunits required at specific times and in finite
      amounts such as those involved in the assembly of flagella, type III secretion
      machines and pili. Finally, phylogenetic analysis suggests that CsrA, a highly
      pleiotropic virulence regulator in many bacterial pathogens, had an ancestral
      role in flagellar assembly and evolved to co-regulate various cellular processes
      with motility.

PMID- 21895795
TI  - Identification of a conserved protein involved in anaerobic unsaturated fatty
      acid synthesis in Neiserria gonorrhoeae: implications for facultative and
      obligate anaerobes that lack FabA.
AB  - Transcriptome analysis of the facultative anaerobe, Neisseria gonorrhoeae,
      revealed that many genes of unknown function were induced under anaerobic
      conditions. Mutation of one such gene, NGO1024, encoding a protein belonging to
      the 2-nitropropane dioxygenase-like superfamily of proteins, was found to result
      in an inability of gonococci to grow anaerobically. Anaerobic growth of an NG1024
      mutant was restored upon supplementation with unsaturated fatty acids (UFA), but
      not with the saturated fatty acid palmitate. Gonococcal fatty acid profiles
      confirmed that NGO1024 was involved in UFA synthesis anaerobically, but not
      aerobically, demonstrating that gonococci contain two distinct pathways for the
      production of UFAs, with a yet unidentified aerobic mechanism, and an anaerobic
      mechanism involving NGO1024. Expression of genes involved in classical anaerobic
      UFA synthesis, fabA, fabM and fabB, was toxic in gonococci and unable to
      complement a NGO1024 mutation, suggesting that the chemistry involved in
      gonococcal anaerobic UFA synthesis is distinct from that of the classical
      pathway. NGO1024 homologues, which we suggest naming UfaA, form a distinct
      lineage within the 2-nitropropane dioxygenase-like superfamily, and are found in
      many facultative and obligate anaerobes that produce UFAs but lack fabA,
      suggesting that UfaA is part of a widespread pathway involved in UFA synthesis.

PMID- 21895796
TI  - Two oppositely oriented arrays of low-affinity recognition sites in oriC guide
      progressive binding of DnaA during Escherichia coli pre-RC assembly.
AB  - The onset of chromosomal DNA replication requires highly precise and reproducible
      interactions between initiator proteins and replication origins to assemble a pre
      replicative complex (pre-RC) that unwinds the DNA duplex. In bacteria, initiator
      protein DnaA, bound to specific high- and low-affinity recognition sites within
      the unique oriC locus, comprises the pre-RC, but how complex assembly is
      choreographed to ensure precise initiation timing during the cell cycle is not
      well understood. In this study, we present evidence that higher-order DnaA
      structures are formed at oriC when DnaA monomers are closely positioned on the
      same face of the DNA helix by interaction with two oppositely oriented essential
      arrays of closely spaced low-affinity DnaA binding sites. As DnaA levels
      increase, peripheral high-affinity anchor sites begin cooperative loading of the
      arrays, which is extended by sequential binding of additional DnaA monomers
      resulting in growth of the complexes towards the centre of oriC. We suggest that
      this polarized assembly of unique DnaA oligomers within oriC plays an important
      role in mediating pre-RC activity and may be a feature found in all bacterial
      replication origins.

PMID- 21895797
TI  - Negative control in two-component signal transduction by transmitter phosphatase
      activity.
AB  - Bifunctional sensor transmitter modules of two-component systems exert both
      positive and negative control on the receiver domain of the cognate response
      regulator. In negative control, the transmitter module accelerates the rate of
      phospho-receiver dephosphorylation. This transmitter phosphatase reaction serves
      the important physiological functions of resetting response regulator
      phosphorylation level and suppressing cross-talk. Although the biochemical
      reactions underlying positive control are reasonably well understood, the
      mechanism for transmitter phosphatase activity has been unknown. A recent
      hypothesis is that the transmitter phosphatase reaction is catalysed by a
      conserved Gln, Asn or Thr residue, via a hydrogen bond between the amide or
      hydroxyl group and the nucleophilic water molecule in acyl-phosphate hydrolysis.
      This hypothetical mechanism closely resembles the established mechanisms of
      auxiliary phosphatases such as CheZ and CheX, and may be widely conserved in two
      component signal transduction. In addition to the proposed catalytic residues,
      transmitter phosphatase activity also requires the correct transmitter
      conformation and appropriate interactions with the receiver. Evidence suggests
      that the phosphatase-competent and autokinase-competent states are mutually
      exclusive, and the corresponding negative and positive activities are likely to
      be reciprocally regulated through dynamic control of transmitter conformations.

PMID- 21895798
TI  - The Lys20 homocitrate synthase isoform exerts most of the flux control over the
      lysine synthesis pathway in Saccharomyces cerevisiae.
AB  - In Saccharomyces cerevisiae, the first committed step in the lysine (Lys)
      biosynthetic pathway is catalysed by the Lys20 and Lys21 homocitrate synthase
      (HCS) isoforms. Overexpression of Lys20 resulted in eightfold increased Lys, as
      well as 2-oxoglutarate pools, which were not attained by overexpressing Lys21 or
      other pathway enzymes (Lys1, Lys9 or Lys12). A metabolic control analysis-based
      strategy, by gradually and individually manipulating the Lys20 and Lys21
      activities demonstrated that the cooperative and strongly feedback-inhibited
      Lys21 isoform exerted low control of the pathway flux whereas most of the control
      resided on the non-cooperative and weakly feedback-inhibited Lys20 isoform.
      Therefore, the higher control of Lys20 over the Lys flux represents an exception
      to the dogma of higher pathway control by the strongest feedback-inhibited enzyme
      and points out to multi-site engineering (HCS isoforms and supply of precursors)
      to increase Lys synthesis.

PMID- 21895799
TI  - Split decision: a thaumarchaeon encoding both FtsZ and Cdv cell division proteins
      chooses Cdv for cytokinesis.
AB  - Cytoskeletal proteins play a pivotal role in cytokinesis in prokaryotes and
      eukaryotes. Most bacteria and a major branch of the archaea called the
      Euryarchaeota harbour a tubulin homologue, FtsZ, which assembles into a dynamic
      polymeric ring structure required for cytokinesis. However, Crenarchaeota,
      another branch of the archaea, lack FtsZ and instead use Cdv proteins, which are
      homologues of the ESCRT-III-like system involved in vesicular sorting and
      cytokinesis in eukaryotes, for cell division. Recently, a group of Crenarchaeota
      that grow in non-extreme environments was found to be sufficiently divergent to
      warrant its own branch of the archaea called the Thaumarchaeota. Notably,
      Thaumarchaeota have both Cdv and FtsZ homologues, which begs the question of
      which system is used for cell division. In this issue of Molecular
      Microbiology,Pelve et al. (2011) Pelve and colleagues tackle this question. They
      found that cells of the thaumarchaeon Nitrosopumilus maritimus likely divide
      using the Cdv system and not FtsZ, based on localization of Cdv proteins but not
      FtsZ to division sites. The authors also provide evidence that the cell cycle
      during growth of N. maritimus differs significantly from those of other archaea.

PMID- 21895800
TI  - Sleep abnormalities in schizophrenia may suggest impaired trans-thalamic cortico
      cortical communication: towards a dynamic model of the illness.
AB  - Schizophrenia is associated with a wide range of symptoms. These include auditory
      hallucinations, delusions, and experiences that one is not in control of one's
      own thoughts and actions, but that they are inserted by an outside agency. It has
      been proposed that a disturbance in the sense of self may account for many of
      these symptoms. This disturbance in turn may be associated with source monitoring
      deficits. In other words, individuals with schizophrenia may misattribute the
      source of their own thoughts and actions to an outside agency, which then results
      in the experience of psychosis such as that of hearing voices. To explain the
      source monitoring deficits, it has been proposed that this illness involves
      impairment in corollary discharge mechanisms. Corollary discharge refers to
      preparation of sensory systems that will be affected by an action in advance of
      that action, which then allows this action to be recognized as one's own. Current
      research on corollary discharges suggests that they may involve the thalamus,
      which is notably affected in schizophrenia in terms of volume loss. Sleep
      abnormalities in this illness also suggest thalamic dysfunction as sleep
      spindles, which are markedly reduced in schizophrenia, require intact
      thalamocortical interactions. In this review, evidence is presented that suggests
      that propagation of corollary discharges and sleep spindles may be two
      mechanistically related processes as both involve trans-thalamic cortico-cortical
      interactions. These interactions may be impaired in schizophrenia and
      characterization of their mechanism may constitute a step towards developing a
      dynamic model of schizophrenia.

PMID- 21895801
TI  - Raphe pallidus modulates Botzinger complex-induced inhibition of the phrenic
      nerve activity in rats.
AB  - The raphe pallidus (RPa) and Botzinger complex (BotC) represent two important
      nuclei which project to spinal phrenic motor neurons. Stimulation of the RPa
      produces facilitative effects on respiratory activity, whereas stimulation of the
      BotC induces inhibitory effects on respiratory activity. In the present study, we
      examined the modulatory effects of serotonergic (5-hydroxytryptamine, 5-HT) RPa
      neurons on the inhibitory response of the phrenic nerve activity elicited from
      the BotC in rats. Experiments were performed on spontaneously breathing, urethane
      anesthetized adult rats. Either high-frequency stimulation or glutamatergic
      chemical activation of the RPa region significantly attenuated the BotC-induced
      inhibition of the phrenic nerve. This attenuation showed a post-stimulation time
      and intensity dependency. Pharmacological experiments showed that intravenous
      injection of methysergide, a broad-spectrum antagonist of 5-HT receptors,
      markedly reduced the respiratory facilitation induced by electrical stimulation
      of the RPa. Furthermore, microinjections of methysergide into the cerebrospinal
      fluid around the phrenic motor nucleus (PMN) region at spinal cord segments C4
      and C5 significantly decreased the RPa-related attenuation effects on BotC-evoked
      inhibition of phrenic nerve discharge. These results suggest that RPa
      serotonergic neurons could modulate the inhibition of phrenic nerve activity
      induced by BotC. Moreover, as the relevant 5-HT receptors for RPa's modulatory
      effects are located in the cervical spinal cord, 5-HT may, in part, function as a
      modulator to suppress the BotC neuronal activity via direct RPa-PMN and BotC-PMN
      convergent projection pathways to phrenic motoneurons.

PMID- 21895802
TI  - Cellular mechanisms underlying the regulation of dendritic development by
      hepatocyte growth factor.
AB  - Acquisition of a mature dendritic morphology is critical for neural information
      processing. In particular, hepatocyte growth factor (HGF) controls dendritic
      arborization during brain development. However, the cellular mechanisms
      underlying the effects of HGF on dendritic growth remain elusive. Here, we show
      that HGF increases dendritic length and branching of rat cortical neurons through
      activation of the mitogen-activated protein kinase (MAPK) signaling pathway.
      Activation of MAPK by HGF leads to the rapid and transient phosphorylation of
      cAMP response element-binding protein (CREB), a key step necessary for the
      control of dendritic development by HGF. In addition to CREB phosphorylation,
      regulation of dendritic growth by HGF requires the interaction between CREB and
      CREB-regulated transcription coactivator 1 (CRTC1), as expression of a mutated
      form of CREB unable to bind CRTC1 completely abolished the effects of HGF on
      dendritic morphology. Treatment of cortical neurons with HGF in combination with
      brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family
      that regulates dendritic development via similar mechanisms, showed additive
      effects on MAPK activation, CREB phosphorylation and dendritic growth.
      Collectively, these results support the conclusion that regulation of cortical
      dendritic morphology by HGF is mediated by activation of the MAPK pathway,
      phosphorylation of CREB and interaction of CREB with CRTC1.

PMID- 21895803
TI  - NR2B-subunit dependent facilitation of long-term potentiation in primary visual
      cortex following visual discrimination training of adult rats.
AB  - Long-term potentiation (LTP) is an important mechanism thought to mediate changes
      in synaptic connectivity following various types of experience. We examined the
      effects of visual discrimination training on LTP in the mature, rodent
      thalamocortical visual system. Adult rats underwent visual discrimination
      training in a modified Morris Water Maze containing a Y-maze insert, requiring
      rats to associate visual cues with the location of a hidden escape platform
      placed in one of the two goal arms of the Y-maze insert. On the day following
      successful task acquisition (average of nine training days), rats were
      anesthetized (urethane), and LTP in the thalamocortical system was characterized.
      In task-naive rats, theta-burst stimulation of the lateral geniculate nucleus
      resulted in modest (~40%) potentiation of field postsynaptic potentials recorded
      in the primary visual cortex (V1). Rats trained on the visual discrimination task
      showed significantly greater levels of LTP (~60%), an effect that was not seen in
      rats trained to swim in the maze without a predictive association between visual
      cues and platform location. An antagonist of the N-methyl-d-aspartate (NMDA)
      receptor NR2B subunit ([R-(R *,S *)]-alpha-(4-hydroxyphenyl)-beta-methyl-4
      (phenylmethyl)-1-piperidinepropanol hydrochloride (Ro 25-6981); 2 mm, applied
      locally at the recording site in V1) reversed the training-induced LTP
      enhancement without affecting LTP in task-naive rats. An antagonist of
      metabotropic glutamate receptors [(2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1
      yl]-3-(xanth-9-yl) propanoic acid (LY 341495); 2 mm] was ineffective in reversing
      the training-induced LTP facilitation. These data suggest that behavioral
      (visual) training can result in changes in plasticity exhibited by the mature,
      thalamocortical visual system that require activation of NMDA receptors
      containing the NR2B subunit.

PMID- 21895804
TI  - Recombinant tissue plasminogen activator induces blood-brain barrier breakdown by
      a matrix metalloproteinase-9-independent pathway after transient focal cerebral
      ischemia in mouse.
AB  - The role of the inducible matrix metalloproteinase (MMP)-9 in blood-brain barrier
      (BBB) disruption after ischemic stroke is well accepted. Recombinant tissue
      plasminogen activator (r-tPA) is the only approved thrombolytic treatment of
      ischemic stroke but r-tPA is potentially neurotoxic. Vasogenic edema after r-tPA
      treatment has been linked with an increase in cerebral MMP-9. However, because
      cerebral ischemia clearly increases the levels of endogenous tPA, the consequence
      of additional r-tPA may be questionable. In this study, wild type and MMP-9
      knockout mice were subjected to 90 min transient middle cerebral artery occlusion
      and treated with 10 mg/kg r-tPA. At 24 h after occlusion, BBB permeability,
      hemispheric enlargement, collagen and laminin degradation as well as cerebral
      infarction were increased in both wild type and MMP-9 knockout treated animals as
      compared with non-treated animals. Mortality was increased in wild type but
      reduced in knockout treated mice. Cerebral MMP-9 concentration was not modified
      by r-tPA. However, pre-treatment with p-aminobenzoyl-gly-pro-D-leu-D-ala
      hydroxamate, a broad-spectrum MMP inhibitor, counteracted the effects of r-tPA on
      the neurovascular unit and decreased mortality in both wild type and knockout
      mice. MMP inhibition did not modify cerebral infarction in r-tPA-treated animals.
      Our results suggest that r-tPA toxicity is mainly independent of MMP-9 after
      transient middle cerebral artery occlusion but could involve some other MMPs.
      Additionally, our results support the hypothesis of a dissociation between r-tPA
      dependent mechanisms of BBB breakdown and cerebral infarction. Due to the
      importance of r-tPA in thrombolytic treatment of ischemic stroke patients, the
      MMPs that could participate in r-tPA-induced BBB disruption should be further
      characterized.

PMID- 21895805
TI  - Absence of compensation for vestibular-evoked passive head rotations in human
      sound localization.
AB  - A world-fixed sound presented to a moving head produces changing sound
      localization cues, from which the audiomotor system could infer sound movement
      relative to the head. When appropriately combined with self-motion signals, sound
      localization remains spatially accurate. Indeed, free-field orienting responses
      fully incorporate intervening eye-head movements under open-loop localization
      conditions. Here we investigate the default strategy of the audiomotor system
      when localizing sounds in the absence of efferent and proprioceptive head
      movement signals. Head- and body-restrained listeners made saccades in total
      darkness toward brief (3, 10 or 100 ms) broadband noise bursts, while being
      rotated sinusoidally (f=1/9 Hz, V(peak) =112 deg/s) around the vertical body
      axis. As the loudspeakers were attached to the chair, the 100 ms sounds might be
      perceived as rotating along with the chair, and localized in head-centred
      coordinates. During 3 and 10 ms stimuli, however, the amount of chair rotation
      remained well below the minimum audible movement angle. These brief sounds would
      therefore be perceived as stationary in space and, as in open-loop gaze
      orienting, expected to be localized in world-centred coordinates. Analysis of the
      saccades shows, however, that all stimuli were accurately localized on the basis
      of imposed acoustic cues, but remained in head-centred coordinates. These results
      suggest that, in the absence of motor planning, the audio motor system keeps
      sounds in head-centred coordinates when unsure about sound motion relative to the
      head. To that end, it ignores vestibular canal signals of passive-induced head
      rotation, but incorporates intervening eye displacements from vestibular
      nystagmus during the saccade-reaction time.

PMID- 21895807
TI  - A protein shot for biomedical research.

PMID- 21895806
TI  - How selective sweeps in domestic animals provide new insight into biological
      mechanisms.
AB  - Genetic studies of domestic animals are of general interest because there is more
      phenotypic diversity to explore in these species than in any experimental
      organism. Some mutations with favourable phenotypic effects have been highly
      enriched and gone through selective sweeps during the process of domestication
      and selective breeding. Three such selective sweeps are described in this review.
      All three mutations are intronic and constitute cis-acting regulatory mutations.
      Two of the mutations constitute structural changes (one duplication and one copy
      number expansion). These examples illustrate a general trend that noncoding
      mutations and structural changes have both contributed significantly to the
      evolution of phenotypic diversity in domestic animals. How the molecular
      characterization of trait loci in domestic animals can provide new basic
      knowledge of relevance for human medicine is discussed.

PMID- 21895808
TI  - Fresh blood for transfusion in adults with beta thalassaemia.
AB  - BACKGROUND: Patients with beta-thalassaemia major require life-long blood
      transfusion with the aim of achieving normal growth and development whilst
      minimising iron overload. A pre-transfusion Hb between 9.5 and 10 g/dL is thought
      to achieve this balance. UK consensus is that fresh blood (less than 14 days) is
      better at maintaining this target pre-transfusion Hb but there is no firm
      stipulation in place and no robust evidence supporting this. METHODS: After
      introduction of a universal fresh blood policy for adult beta-thalassaemics in
      2010, we reviewed locally transfused adult patients to determine if there was any
      significant difference in pre-transfusion Hb using fresh blood. Nine adult
      thalassaemic patients were analysed for two consecutive 6-month periods in 2009
      and 2010 (periods 1 and 2). RESULTS: Mean pre-transfusion Hb was significantly
      higher by an average of 0.5 g/dL in period 2 than period 1 (P < 0.05). The
      average unit age was 18 vs 9.5 days for periods 1 and 2 respectively (P < 0.05).
      There were no significant differences in potential confounders such as
      transfusion volume (P = 0.06), number of units transfused, ferritin or
      transfusion interval. DISCUSSION: Use of fresh blood produced significantly
      higher pre-transfusion Hb, giving credence to UK consensus. Lesser volumes of
      fresh blood appeared to achieve the target pre-transfusion Hb, which may
      translate to reduced iron overload and chelation costs. Whether the assumption
      that the use of blood less than 7 days old in these patients would result in
      greater benefit requires further study.

PMID- 21895809
TI  - Evaluation of two detection methods of microorganisms in platelet concentrates.
AB  - BACKGROUND: The performance of a bacterial 16S ribosomal DNA real-time polymerase
      chain reaction (PCR) assay was evaluated and validated with an automated culture
      system to determine its use for screening of platelet concentrates (PCs). STUDY
      DESIGN AND METHODS: PCs were spiked with suspensions of Escherichia coli,
      Serratia marcescens, Staphylococcus epidermidis and St. aureus at 1, 10, and 100
      colony-forming units (CFUs) mL and stored for 5 days. DNA amplification was
      performed using real-time PCR. The BacT/ALERT was used as a reference method and
      samples were inoculated into an aerobic culture bottle; for the PCR assay,
      aliquots were drawn from all (spiked) PCs on days 0 to 5 of storage. RESULTS:
      Real-time PCR detected only the gram-positive bacteria in PCs spiked with low
      bacterial titres (1 CFU mL) after 48 h; however, it was able to detect all
      positive samples in PCs spiked with 10 CFU mL of either gram-positive or gram
      negative bacteria after 48 h. In addition, real-time PCR detected all positive
      samples in PCs spiked with high gram-positive bacterial titres (100 CFU mL) after
      24 h. On the other hand, the BacT/ALERT system showed positive results in all
      samples within 24 h. CONCLUSION: The BacT/ALERT method is more sensitive and
      should continue to be the gold standard for identifying bacterial contaminations
      in blood samples. The real-time PCR approach can be used for the screening of PCs
      for microbial detection before they are released from blood centres or shortly
      before they are used in blood transfusion, and thus allow an extended shelf life
      of the platelets.

PMID- 21895810
TI  - A peroxisomal carrier delivers NAD+ and contributes to optimal fatty acid
      degradation during storage oil mobilization.
AB  - The existence of a transport protein that imports cytosolic NAD(+)  into
      peroxisomes has been controversially discussed for decades. Nevertheless, the
      biosynthesis of NAD(+)  in the cytosol necessitates the import of NAD(+)  into
      peroxisomes for numerous reduction/oxidation (redox) reactions. However, a gene
      encoding such a transport system has not yet been identified in any eukaryotic
      organism. Here, we describe the peroxisomal NAD(+)  carrier in Arabidopsis. Our
      candidate gene At2g39970 encodes for a member of the mitochondrial carrier
      family. We confirmed its peroxisomal localization using fluorescence microscopy.
      For a long time At2g39970 was assumed to represent the peroxisomal ATP
      transporter. In this study, we could show that the recombinant protein mediated
      the transport of NAD(+) . Hence, At2g39970 was named PXN for peroxisomal NAD(+) 
      carrier. The loss of PXN in Arabidopsis causes defects in NAD(+) -dependent beta
      oxidation during seedling establishment. The breakdown of fatty acid released
      from storage oil was delayed, which led to the retention of oil bodies in pxn
      mutant seedlings. Based on our results, we propose that PXN delivers NAD(+)  for
      optimal fatty acid degradation during storage oil mobilization.

PMID- 21895812
TI  - Genome-wide transcriptome dissection of the rice root system: implications for
      developmental and physiological functions.
AB  - The root system is a crucial determinant of plant growth potential because of its
      important functions, e.g. uptake of water and nutrients, structural support and
      interaction with symbiotic organisms. Elucidating the molecular mechanism of root
      development and functions is therefore necessary for improving plant
      productivity, particularly for crop plants, including rice (Oryza sativa). As an
      initial step towards developing a comprehensive understanding of the root system,
      we performed a large-scale transcriptome analysis of the rice root via a combined
      laser microdissection and microarray approach. The crown root was divided into
      eight developmental stages along the longitudinal axis and three radial tissue
      types at two different developmental stages, namely: epidermis, exodermis and
      sclerenchyma; cortex; and endodermis, pericycle and stele. We analyzed a total of
      38 microarray data and identified 22,297 genes corresponding to 17,010 loci that
      showed sufficient signal intensity as well as developmental- and tissue type
      specific transcriptome signatures. Moreover, we clarified gene networks
      associated with root cap function and lateral root formation, and further
      revealed antagonistic and synergistic interactions of phytohormones such as
      auxin, cytokinin, brassinosteroids and ethylene, based on the expression pattern
      of genes related to phytohormone biosynthesis and signaling. Expression profiling
      of transporter genes defined not only major sites for uptake and transport of
      water and nutrients, but also distinct signatures of the radial transport system
      from the rhizosphere to the xylem vessel for each nutrient. All data can be
      accessed from our gene expression profile database, RiceXPro
      (http://ricexpro.dna.affrc.go.jp), thereby providing useful information for
      understanding the molecular mechanisms involved in root system development of
      crop plants.

PMID- 21895811
TI  - The TFL1 homologue KSN is a regulator of continuous flowering in rose and
      strawberry.
AB  - Flowering is a key event in plant life, and is finely tuned by environmental and
      endogenous signals to adapt to different environments. In horticulture,
      continuous flowering (CF) is a popular trait introduced in a wide range of
      cultivated varieties. It played an essential role in the tremendous success of
      modern roses and woodland strawberries in gardens. CF genotypes flower during all
      favourable seasons, whereas once-flowering (OF) genotypes only flower in spring.
      Here we show that in rose and strawberry continuous flowering is controlled by
      orthologous genes of the TERMINAL FLOWER 1 (TFL1) family. In rose, six
      independent pairs of CF/OF mutants differ in the presence of a retrotransposon in
      the second intron of the TFL1 homologue. Because of an insertion of the
      retrotransposon, transcription of the gene is blocked in CF roses and the absence
      of the floral repressor provokes continuous blooming. In OF-climbing mutants, the
      retrotransposon has recombined to give an allele bearing only the long terminal
      repeat element, thus restoring a functional allele. In OF roses, seasonal
      regulation of the TFL1 homologue may explain the seasonal flowering, with low
      expression in spring to allow the first bloom. In woodland strawberry, Fragaria
      vesca, a 2-bp deletion in the coding region of the TFL1 homologue introduces a
      frame shift and is responsible for CF behaviour. A diversity analysis has
      revealed that this deletion is always associated with the CF phenotype. Our
      results demonstrate a new role of TFL1 in perennial plants in maintaining
      vegetative growth and modifying flowering seasonality.

PMID- 21895813
TI  - Accuracy of population-specific Demirjian curves in the estimation of dental age
      of Saudi children.
AB  - BACKGROUND: The Demirjian eight-stage method is one of the principal methods used
      to quantify the degree of maturity from age 3 to 17. Aim.  The objective of this
      study was to compare the accuracy of dental age of different population-specific
      curves, derived using the Demirjian method, to the chronological age of Saudi
      children aged between 4 and 14. DESIGN: Panoramic radiographic records of 176
      children (91 boys and 85 girls), without any history of systemic disease, were
      assessed using the Demirjian method, and the dental age was calculated using
      curves designed for French-Canadian, Belgian, Kuwaiti, and Saudi children. The
      difference from chronological age (DA-CA) for each curve was then statistically
      compared using ANOVA, and each of the curves was compared to the chronological
      age using multinomial regression modelling. RESULTS: The results suggest that
      although population-specific curves are more accurate in the prediction of age, a
      considerable variation within each population still exists. CONCLUSIONS: The
      Demirjian method offers great scope in fields that require the study of the
      pattern of growth rather than the accuracy of age estimation.

PMID- 21895814
TI  - Psychological distress and unmet supportive care needs in cancer patients and
      carers who contact cancer helplines.
AB  - Cancer information services are a highly accessible source of support for people
      affected by cancer. To date the nature and extent of distress experienced by such
      callers and their unmet support needs have not been well described. A cross
      sectional survey of 354 cancer patients and 336 carers who reported elevated
      distress on contact with a cancer information service assessed socio-demographic
      variables; anxiety, depression and somatization; unmet supportive care needs;
      cancer-specific distress; presenting problems; post-traumatic growth. Adjustment
      to cancer was most commonly reported; followed by anxiety. In all, 53.4% of
      patients and 45.2% of carers reached caseness in anxiety, depression or
      somatization. Carers had higher distress ratings and intrusive thinking compared
      to patients; whereas patients had higher somatization. For patients, most unmet
      supportive care needs were psychological; for carers unmet needs were related to
      health care services and information related to the person diagnosed with cancer.
      Being single, unemployed, in treatment, having higher initial distress scores,
      higher intrusion and avoidance predicted poorer outcomes. Information service
      frameworks should include distress screening and clear triage and referral
      processes for psychological care.

PMID- 21895815
TI  - Primary caregivers' satisfaction with clinicians' response to them as informal
      carers of young people with first-episode psychosis: a qualitative study.
AB  - AIM: To explore first-time primary caregivers' experience of the way mental
      health nurses and other mental health clinicians respond to them as carers of
      young people with first-episode psychosis. BACKGROUND: Caregivers have a key role
      in supporting family members/relatives with mental illness, but their
      contribution is undervalued frequently by mental health nurses and other mental
      health clinicians. Design.  Qualitative interpretative phenomenological analysis.
      METHOD: A qualitative interpretative design was undertaken, using semi
      structured, audio-recorded interviews. Twenty primary caregivers were recruited
      through Orygen Youth Health, a first-episode psychosis centre in Melbourne.
      Interpretative phenomenological analysis was used to identify themes in the data.
      RESULTS: Two competing themes were identified in the data, highlighting
      caregivers' contrasting experience with mental health nurses and other mental
      health clinicians. First, most clinical staff were approachable and supportive.
      Second, several carers felt their contribution was undervalued by some clinical
      staff. This was as a consequence of being excluded from clinical deliberations
      because of clinical staffs' concerns and young people's requests about
      maintaining confidentiality regarding treatment, as well as carers feeling their
      role was not taken seriously by clinical staff. CONCLUSION: First-time primary
      carers have positive and negative experiences with first-episode psychosis mental
      health nurses and other clinicians, and these competing events are interrelated.
      Experiences are affected directly by the manner they are treated by clinical
      staff and this may, in turn, affect carers' commitment to caring, the way they
      engage with clinical staff on subsequent occasions and towards the first-episode
      psychosis service generally. RELEVANCE TO CLINICAL PRACTICE: Greater appreciation
      is needed of the contribution, experience and difficulties caregivers encounter
      in their role and in engaging with mental health nurses and other clinicians.
      Additional training is required for clinical staff in family interventions and to
      familiarise them with legislation and mental health policies relating to carers.

PMID- 21895816
TI  - Approaches for dealing with missing data in health care studies.
AB  - AIM: The aims of this study were to highlight the problems associated with
      missing data in healthcare research and to demonstrate the use of several
      techniques for dealing with missing values, through the use of an illustrative
      example. BACKGROUND: In healthcare research studies, it is almost impossible to
      avoid at least some missing values during data collection, which in turn can
      threaten the validity of the study conclusions. A range of methods for reducing
      the impact of missing data on the validity of study findings have been developed,
      depending on the nature and patterns which the missing values may take. DESIGN: A
      discursive study. METHODS: Several techniques designed to deal with missing data
      are described and applied to an illustrative example. These methods include
      complete-case analysis, available-case analysis, as well as single and multiple
      imputation. CONCLUSIONS: If research data contain missing values that are not
      randomly distributed, then the study results are likely to be biased unless an
      effective approach to dealing with the missing values is implemented. RELEVANCE
      TO CLINICAL PRACTICE: If nursing and healthcare practice is to be informed by
      research findings, then these findings must be reliable and valid. Researchers
      should report the details of missing data, and appropriate methods for dealing
      with missing values should be incorporated into the data analysis.

PMID- 21895817
TI  - Brief exposures of human body lice to sublethal amounts of ivermectin over
      transcribes detoxification genes involved in tolerance.
AB  - Transcriptional profiling results, using our non-invasive induction assay {short
      exposure intervals (2-5 h) to sublethal amounts of insecticides [< lethal
      concentration 3% (LC(3)) at 24 h] administered by stress-reducing means (contact
      vs. immersion screen) and with induction assessed in a time frame when tolerance
      is still present [~lethal concentration 90% (LC(90)) in 2-4 h]}, showed that
      ivermectin-induced detoxification genes from body lice are identified by
      quantitative real-time PCR analyses. Of the cytochrome P450 monooxygenase and ATP
      binding cassette transporter genes induced by ivermectin, CYP6CJ1, CYP9AG1,
      CYP9AG2 and PhABCC4 were respectively most significantly over-expressed, had high
      basal expression levels and were most closely related to genes from other
      organisms that metabolized insecticides, including ivermectin. Injection of
      double-stranded RNAs (dsRNAs) against either CYP9AG2 or PhABCC4 into non-induced
      female lice reduced their respective transcript level and resulted in increased
      sensitivity to ivermectin, indicating that these two genes are involved in the
      xenobiotic metabolism of ivermectin and in the production of tolerance.

PMID- 21895818
TI  - An update on mosquito cell expressed dengue virus receptor proteins.
AB  - Dengue is the most important mosquito transmitted viral disease of humans
      worldwide. Despite intensive study over several decades, many of the fine details
      of the dengue virus (DENV) replication cycle remain unknown, although generally
      more is known about the phase of the replication cycle in mammalian cells as
      compared to the phase in mosquito cells. This results from a combination of less
      research emphasis on the mosquito stage, as well as fewer tools such as specific
      antibodies against mosquito proteins and insect informatics databases. The
      binding of a virus to a host cell is a first and critical stage in the infectious
      process and the mechanism and identity of cellular proteins involved in this
      process remains largely unknown. This short review aims to provide an update on
      our current understanding of the proteins expressed by mosquito cells that
      mediate DENV binding as a prerequisite to DENV entry and replication.

PMID- 21895819
TI  - Influence of hormone response elements (HREs) on ecdysteroid receptor
      concentration.
AB  - Transcriptional activity of nuclear receptors is the result of transactivation
      capability and receptor protein concentration. The concentration of ecdysteroid
      receptor (EcR) constitutively expressed in vertebrate cells varies depending on
      the isoforms. Besides ligand binding and heterodimerization with ultraspiracle
      (USP), which stabilizes receptor protein concentration, degradation is regulated
      by interaction of the receptor complex with different ecdysteroid response
      elements (EcREs). Coexpression of EcREs significantly reduces ecdysteroid
      receptor concentration depending on the type of EcRE. Transcriptional activity
      and interaction with hormone response elements (HREs) as determined by
      Electrophoretic Mobility Shift Assay (EMSA) are often inversely related to
      receptor protein concentration. The complex regulation of receptor protein
      concentration offers an additional opportunity to regulate transcriptional
      activity in an isoform- and target cell-specific manner and allows the temporal
      limitation of hormone action.

PMID- 21895820
TI  - Bayesian inference of a historical bottleneck in a heavily exploited marine
      mammal.
AB  - Emerging Bayesian analytical approaches offer increasingly sophisticated means of
      reconstructing historical population dynamics from genetic data, but have been
      little applied to scenarios involving demographic bottlenecks. Consequently, we
      analysed a large mitochondrial and microsatellite dataset from the Antarctic fur
      seal Arctocephalus gazella, a species subjected to one of the most extreme
      examples of uncontrolled exploitation in history when it was reduced to the brink
      of extinction by the sealing industry during the late eighteenth and nineteenth
      centuries. Classical bottleneck tests, which exploit the fact that rare alleles
      are rapidly lost during demographic reduction, yielded ambiguous results. In
      contrast, a strong signal of recent demographic decline was detected using both
      Bayesian skyline plots and Approximate Bayesian Computation, the latter also
      allowing derivation of posterior parameter estimates that were remarkably
      consistent with historical observations. This was achieved using only
      contemporary samples, further emphasizing the potential of Bayesian approaches to
      address important problems in conservation and evolutionary biology.

PMID- 21895821
TI  - Natural killer cells in free-living Mus musculus have a primed phenotype.
AB  - Recent reports have shown that natural killer (NK) cells may be long-lived,
      possess memory-like features and may need microbial priming to become fully
      reactive. Thus, the notion that these cells are typically innate, nonadaptive
      lymphocytes has been challenged. If microbial priming is essential for functional
      maturity, it is necessary to raise the question whether NK cells of laboratory
      mice, kept under strict hygienic conditions, represent these cells adequately. In
      their natural habitat, mice will encounter microbes to a greater extent, and we
      here investigated whether NK cells of feral mice showed signs of being primed. In
      comparison with C57BL/6 mice raised under specific pathogen-free conditions, NK
      cells from feral mice had high expression of CD69, KLRG1, granzyme B and NKp46
      and a higher proportion of CD27+ cells, mostly CD11b-, as well as a higher
      presence in peripheral lymph nodes. Following cytokine stimulation, feral mouse
      NK cells had quickly inducible CD25 expression and a stronger interferon-gamma
      response. These findings indicate a high degree of pre-activation of NK cells of
      free-living mice, indicating a strong environmental impact on NK cells, which may
      be highly relevant for interpretation of studies in the mouse model.

PMID- 21895822
TI  - Relationship between sleep-disordered breathing and markers of systemic
      inflammation in women from the general population.
AB  - Sleep-disordered breathing (SDB) is a risk factor for cardiovascular disease
      (CVD). The underlying pathogenesis is not clear. In patients with obstructive
      sleep apnoea syndrome (OSAS) elevated levels of inflammatory markers, such as C
      reactive protein (CRP), interleukin-6 (IL-6) and tumour necrosis factor alpha
      (TNFalpha) have been found. These markers have also been shown as independent
      markers of CVD in other populations. The aim of the study was to investigate the
      association between SDB and systemic inflammation in a population-based cohort of
      women. From 6817 women who previously answered a questionnaire concerning snoring
      habits, 230 habitually snoring women and 170 women regardless of snoring status
      went through polysomnography, anthropometric measurements and blood sampling.
      Analyses were made for CRP, TNFalpha, IL-6, myeloperoxidase (MPO) and lysozyme.
      The levels of CRP, IL-6 and lysozyme were significantly higher in subjects with
      apnoea-hypopnoea index (AHI) >=15 compared with women with lower AHI. All
      inflammatory markers except MPO correlated to AHI and oxygen desaturation
      measures, and to waist circumference. In multiple linear regressions adjusting
      for age, waist circumference and smoking, independent correlations between oxygen
      desaturation indices (ODI) and inflammation were found for IL-6 (P = 0.03 for %
      sleep time with saturation <90%) and TNFalpha (P = 0.03 for ODI 3%). No
      significant correlations were found between AHI and inflammation. Also, for women
      from the general population there is an independent correlation between SDB and
      inflammation, even after adjusting for obesity. The results indicate that
      intermittent hypoxia, and not the AHI, is related to systemic inflammation seen
      in OSAS.

PMID- 21895823
TI  - Basing drug scheduling decisions on scientific ranking of harmfulness: false
      promise from false premises.
AB  - In recent years a number of studies have attempted to rank drugs by a single
      measure of harmfulness as the basis for decisions about scheduling and
      classification. These efforts are fundamentally flawed, both conceptually and
      methodologically. The effort to provide a single measure masks the variety of non
      comparable dimensions that are relevant, the fact that benefits are ignored for
      most, but not all, drugs and that the harms of a drug are not invariant to the
      policy regime chosen. Methodologically, the most prominent recent effort ignores
      drug interactions and mixes aggregate and individual harms inappropriately.
      Instead we suggest that multiple dimensions of harm need to be displayed to
      inform human judgments of what drugs should be scheduled. Harm is not usefully
      reducible to a single dimension, and even perfect rankings would not constitute a
      'sufficient statistic' for determining scheduling decisions.

PMID- 21895824
TI  - Nutt et al.'s harm scales for drugs--room for improvement but better policy based
      on science with limitations than no science at all.

PMID- 21895825
TI  - Let not the best be the enemy of the good.

PMID- 21895826
TI  - Can harm ratings be useful?

PMID- 21895827
TI  - Scales and blinkers, motes and beams--whose view is obstructed on drug
      scheduling?

PMID- 21895828
TI  - Improved ranking of drugs on harmfulness can bring sense and order to a failed
      system.

PMID- 21895829
TI  - A systematic review of methamphetamine precursor regulations.
AB  - AIMS: To assess the effectiveness of methamphetamine precursor regulations in
      reducing illicit methamphetamine supply and use. METHODS: A systematic review of
      12 databases was used to identify studies that had evaluated the impact of
      methamphetamine precursor regulations on methamphetamine supply and/or use. The
      guidelines of the Effective Practice and Organization of Care Group (EPOC) of The
      Cochrane Collaboration were used to determine which study designs were included
      and assess their quality. RESULTS: Ten studies met the inclusion criteria. These
      studies evaluated 15 interventions (13 regulations and two related interdiction
      efforts), all of which were located in North America. Interventions had
      consistent impacts across various indicators of methamphetamine supply and use.
      Seven of the 15 interventions produced reductions in methamphetamine indicators
      (ranging from 12% to 77%). Two of the largest impacts were seen following
      interdiction efforts, involving the closure of rogue pharmaceutical companies.
      There was no evidence of a shift into other types of drug use, or injecting use,
      although the impact on the synthetic drug market was not examined. Null effects
      were related largely to the existence of alternative sources of precursor
      chemicals or the availability of imported methamphetamine. CONCLUSIONS:
      Methamphetamine precursor regulations can reduce indicators of methamphetamine
      supply and use. Further research is needed to determine whether regulations can
      be effective outside North America, particularly in developing countries, and
      what impact they have on the broader synthetic drug market. Improved data on
      precursor diversion are needed to facilitate the evaluation of precursor
      regulations.

PMID- 21895831
TI  - Predictors of recurrence in patients undergoing cryoballoon ablation for
      treatment of atrial fibrillation: the independent role of sleep-disordered
      breathing.
AB  - INTRODUCTION: In patients with atrial fibrillation (AF) undergoing pulmonary vein
      isolation, cryoballoon technique (cryoPVI) has been adopted in many centers. This
      study aimed to evaluate predictors of AF recurrence including impact of sleep
      disordered breathing (SDB). METHODS AND RESULTS: In 82 patients consecutively
      assigned to cryoPVI cardiorespiratory screening for SDB, assessment of medical
      history, ECG, echocardiography, standard laboratory measurement, and blood gas
      analysis were performed prior to intervention. After a 3-month blanking period, a
      7-day Holter ECG was performed at 3, 6 and then every 6 months to determine AF
      recurrence. Seventy-five patients (69 paroxysmal AF, 6 persistent AF, 22 female,
      age 60 +/- 9 years) completed at least 6-month follow-up. Median follow-up of 12
      months (interquartile range 6-18 months) confirmed maintenance of sinus rhythm in
      69.4% of these patients. Stepwise forward regression model revealed moderate to
      severe SDB (cut-off apnea-hypopnea-index (AHI) >= 15 per hour; Hazard Ratio (HR)
      2.95, P = 0.04), early recurrence of AF (HR 8.74, P < 0.001), persistent AF (HR
      7.16, P < 0.001), preprocedural class III-antiarrhythmic drug treatment (HR 3.63,
      P = 0.02), but not SDB per se (AHI >= 5 per hour) as independent predictors for
      AF recurrence. CONCLUSION: Moderate to severe SDB is a treatable condition that
      independently predicts AF recurrence in patients undergoing cryoPVI. Screening
      for SDB and adequate treatment may improve long-term success of cryoPVI.

PMID- 21895832
TI  - Prevention through intervention: catheter ablation to reduce the rate of
      progression of paroxysmal to persistent atrial fibrillation.

PMID- 21895833
TI  - Long-term insertable loop monitors: how much should we watch to get an answer
      (diagnosis)?

PMID- 21895834
TI  - Noninvasive imaging of sinus node disease: can it predict the need for pacemaker
      implantation?

PMID- 21895835
TI  - The effect of mechanical cycling and different misfit levels on Vicker's
      microhardness of retention screws for single implant-supported prostheses.
AB  - PURPOSE: The aim of this study was to evaluate the effect of mechanical cycling
      and different misfit levels on Vicker's microhardness of retention screws for
      single implant-supported prostheses. MATERIALS AND METHODS: Premachined UCLA
      abutments were cast with cobalt-chromium alloy to obtain 48 crowns divided into
      four groups (n = 12). The crowns presented no misfit in group A (control group)
      and unilateral misfits of 50 MUm, 100 MUm, and 200 MUm in groups B, C, and D,
      respectively. The crowns were screwed to external hexagon implants with titanium
      retention screws (torque of 30 N/cm), and the sets were submitted to three
      different periods of mechanical cycling: 2*10(4) , 5*10(4) , and 1*10(6) cycles.
      Screw microhardness values were measured before and after each cycling period.
      Data were evaluated by two-way ANOVA and Tukey's test (p < 0.05). RESULTS:
      Mechanical cycling statistically reduced microhardness values of retention screws
      regardless of cycling periods and groups. In groups A, B, and C, initial
      microhardness values were statistically different from final microhardness values
      (p < 0.05). There was no statistically significant difference for initial screw
      microhardness values (p > 0.05) among the groups; however, when the groups were
      compared after mechanical cycling, a statistically significant difference was
      observed between groups B and D (p < 0.05). CONCLUSIONS: Mechanical cycling
      reduced the Vicker's microhardness values of the retention screws of all groups.
      The crowns with the highest misfit level presented the highest Vicker's
      microhardness values.

PMID- 21895836
TI  - Higher level taxonomy and molecular phylogenetics of the Choanoflagellatea.
AB  - The choanoflagellates (Choanoflagellatea) comprise a major group of
      nanoflagellates, which are ubiquitous in the aquatic environment. Recent
      molecular phylogenies have shown them to be the sister group to the Metazoa.
      However, the phylogeny of the choanoflagellates is still far from understood. We
      present here a 29 taxon, multigene phylogeny that robustly places the root of the
      choanoflagellates. One of the original nonloricate families, Codonosigidae is
      shown to be a polyphyletic assemblage nested within the Salpingoecidae. We
      elaborate on a revised taxonomy that divides Choanoflagellatea into two orders:
      Craspedida and Acanthoecida. Craspedida is composed of species that possess an
      organic cell coating and contains the single family Salpingoecidae. Members of
      the predominantly marine Acanthoecida produce a siliceous lorica in addition to
      an organic coat and are contained in two families--the Acanthoecidae and
      Stephanoecidae fam. n. Previous studies of choanoflagellates have been hindered
      by cases of taxon misidentification as well as the limited resolution of 18S
      small subunit (SSU) rDNA phylogenies. Unfortunately, cases of misidentification
      have been heavily repeated in the literature. In an attempt to avoid further
      confusion, we highlight known instances of misnamed taxa. We also examine the
      suitability of SSU rDNA sequences alone for choanoflagellate phylogenetics and
      recommend the use of protein-coding genes, such as hsp90 and tubA, whenever
      possible.

PMID- 21895837
TI  - Free sterol composition of species in the dinoflagellate genus Pyrocystis: a
      spectrum of sterol diversity.
AB  - The dinoflagellate genus Pyrocystis includes a small number of marine species,
      which spend the majority of their life cycles as nonmotile cells within a
      carbohydrate sheath, and which are found ubiquitously throughout the world's
      oceans. The biochemistry of this model dinoflagellate genus has been widely
      studied due to its ability to bioluminesce. However, Pyrocystis has been
      comparatively understudied with respect to its lipid biochemistry, in particular
      that of sterols. To date, examination of the sterols of Pyrocystis has focused
      primarily upon Pyrocystis lunula, which produces cholesterol and 4,24-dimethyl
      5alpha-cholestan-3beta-ol as its predominant sterols, while it lacks the common
      dinoflagellate sterol, dinosterol. We have examined the sterol composition of the
      two other commercially available species of Pyrocystis, Pyrocystis fusiformis and
      Pyrocystis noctiluca. Pyrocystis noctiluca possesses dinosterol as its most
      abundant sterol, while P. fusiformis possesses dinosterol and 4,24-dimethyl
      5alpha-cholestan-3beta-ol as the predominant sterols, placing it at an
      intermediate position between P. lunula and P. noctiluca, as based on sterol
      composition. The potential limitations of the dinoflagellate sterol biomarker
      dinosterol are also explored in this study due to its notable absence in P.
      lunula.

PMID- 21895838
TI  - Naegleria fowleri: enolase is expressed during cyst differentiation.
AB  - Cysts of Naegleria fowleri present an external single-layered cyst wall. To date,
      little information exists on the biochemical components of this cyst wall.
      Knowledge of the cyst wall composition is important to understand its resistance
      capacity under adverse environmental conditions. We have used of a monoclonal
      antibody (B4F2 mAb) that specifically recognizes enolase in the cyst wall of
      Entamoeba invadens. By Western blot assays this antibody recognized in soluble
      extracts of N. fowleri cysts a 48-kDa protein with similar molecular weight to
      the enolase reported in E. invadens cysts. Immunofluorescence with the B4F2 mAb
      revealed positive cytoplasmic vesicles in encysting amebas, as well as a positive
      reaction at the cell wall of mature cysts. Immunoelectron microscopy using the
      same monoclonal antibody confirmed the presence of enolase in the cell wall of N.
      fowleri cysts and in cytoplasmic vesicular structures. In addition, the B4F2 mAb
      had a clear inhibitory effect on encystation of N. fowleri.

PMID- 21895839
TI  - Morphology and molecular phylogeny of Pseudotrichonympha hertwigi and
      Pseudotrichonympha paulistana (Trichonymphea, parabasalia) from neotropical
      rhinotermitids.
AB  - Pseudotrichonympha is a large hypermastigote parabasalian found in the hindgut of
      several species of rhinotermitid termites. The genus was discovered more than 100
      years ago, and although over a dozen species have since been described, this
      represents only a small fraction of its likely diversity: the termite genera from
      which Pseudotrichonympha is known are all species rich, and in most cases their
      hindgut symbionts have not been examined. Even formally described species are
      mostly lacking in detailed microscopic data and/or sequence data. Using small
      subunit ribosomal RNA gene sequences and light and scanning electron microscopy
      we describe here the morphology and molecular phylogenetic position of two
      Pseudotrichonympha species: the type species for the genus, Pseudotrichonympha
      hertwigi from Coptotermes testaceus (described previously in line drawing only),
      and Pseudotrichonympha paulistana from Heterotermes tenuis (described previously
      based on light microscopy only).

PMID- 21895840
TI  - Apotrachelocerca arenicola (Kahl, 1933) n. g., comb. n. (Protozoa, Ciliophora,
      Trachelocercidae): morphology and phylogeny.
AB  - During faunistic study on psammophilic ciliates along the coast of Qingdao,
      China, a population of Trachelocerca arenicola Kahl, 1933 was found and then
      investigated using silver staining and gene sequencing methods. The results
      indicated that it represented a new genus Apotrachelocerca characterized by
      uninterrupted circumoral kineties composed of two rows of dikinetids and no
      brosse or ciliary tuft in the oral cavity. This new genus should be assigned to
      the family Prototrachelocercidae Foissner, 1996. Based on the small subunit rRNA
      gene sequence, phylogenetic trees revealed that Apotrachelocerca arenicola
      occupied a basal position to other trachelocercids.

PMID- 21895841
TI  - Complete sequence and gene organization of the Nosema heliothidis ribosomal RNA
      gene region.
AB  - By sequencing the entire ribosomal RNA (rRNA) gene region of Nosema heliothidis
      isolated from cotton bollworm (Helicoverpa armigera), we showed that its gene
      organization is similar to the type species, Nosema bombycis: the 5'-large
      subunit rRNA (2,490 bp)-internal transcribed spacer (192 bp)-small subunit rRNA
      (1,232 bp)-intergenic spacer (274 bp)-5S rRNA (115 bp)-3'. We constructed two
      phylogenetic trees, analyzed phylogenetic relationships, examined rRNA
      organization of microsporidia, and compared the secondary structure of small
      subunit rRNA with closely related microsporidia. The latter two features may
      provide important information for the classification and phylogenetic analysis of
      microsporidia.

PMID- 21895842
TI  - Feeding by the newly described, nematocyst-bearing heterotrophic dinoflagellate
      Gyrodiniellum shiwhaense.
AB  - We explored the feeding ecology of the newly described, nematocyst-bearing
      heterotrophic dinoflagellate Gyrodiniellum shiwhaense (GenBank accession
      number=FR720082). Using several different types of microscopes and high
      resolution video-microscopy, we investigated feeding behavior and types of prey
      species that G. shiwhaense feeds upon. Additionally, we measured its growth and
      ingestion rates on its optimal algal prey, the cryptophyte Teleaulax sp. and the
      dinoflagellate Amphidinium carterae, as a function of prey concentration. These
      rates were measured for other edible prey at single prey concentrations at which
      the growth and ingestion rates of G. shiwhaense were saturated. After anchoring
      the prey with a tow filament, G. shiwhaense fed using a peduncle, ingesting small
      algal species with equivalent spherical diameters (ESDs) of <13 MUm. However, it
      did not feed on larger algal species that had ESDs>=13 MUm or the small diatom
      Skeletonema costatum. The specific growth rates for G. shiwhaense feeding upon
      Teleaulax sp. and A. carterae increased rapidly with increasing mean prey
      concentration before saturating at concentrations of ca. 180-430 ng C/ml. The
      maximum specific growth rate of G. shiwhaense on Teleaulax sp. and A. carterae
      were 1.05 and 0.82/d, respectively. However, Heterosigma akashiwo did not support
      positive growth of G. shiwhaense. The maximum ingestion rates of G. shiwhaense on
      Teleaulax sp. and A. carterae were 0.35 and 0.54 ng C/grazer/d, respectively. The
      calculated grazing coefficients attributable to G. shiwhaense on co-occurring
      cryptophytes and Amphidinium spp. were 0.01-1.87/d and 0.08-2.60/d, respectively.
      Our results suggest that G. shiwhaense can have a considerable grazing impact on
      algal populations.

PMID- 21895843
TI  - Heterologous expression of the CYP51 gene of the obligate fungus Blumeria
      graminis in the necrotrophic fungus Botrytis cinerea.
AB  - As it is extremely difficult to make DNA transformation for the obligate fungus,
      Blumeria graminis f. sp. tritici (Bgt), we developed a heterologous expression
      system for characterization of a Bgt gene, CYP51, which encodes 14alpha
      demethylase. The CYP51 gene from Bgt was transformed into the necrotrophic
      fungus, Botrytis cinerea. Reverse transcription polymerase chain reaction showed
      that the Bgt CYP51 was transcribed in B. cinerea. Green fluorescence was observed
      in the transformants of B. cinerea carrying the Bgt CYP51-GFP fusion cassette,
      suggesting that its translation was successful. Fungicide sensitivity tests
      revealed that B. cinerea transformed with Bgt CYP51 showed reduced sensitivity to
      a sterol demethylation inhibitor triadimefon, but not to a benzimidazole
      fungicide carbendazim. These results indicated that this heterologous expression
      system can be used for functional analysis of other Bgt genes.

PMID- 21895844
TI  - Light and ultrastructural description of Meglitschia mylei n. sp. (myxozoa) from
      Myleus rubripinnis (Teleostei: Serrasalmidae) in the Amazon River system.
AB  - Meglitschia mylei n. sp. found in the gall bladder of the teleostean fish Myleus
      rubripinnis (Serrasalmidae) from the middle Amazonian region of Brazil is
      described using light and transmission electron microscopy. The spores observed
      in the bile averaged 24.6+/-0.8 MUm long, 8.7+/-0.4 MUm wide and 5.1+/-0.3 MUm
      thick and were strongly furcate and arcuate ?-shaped composed of two symmetric
      equal-sized valves, up to ~70 nm thick. Each valve possessed one opposed tapering
      appendage, 20.1+/-0.7 MUm long, oriented parallel towards the basal tip of the
      appendages and joined along a right suture line forming a thick strand. The
      strand goes around the central part of the spore, which in turn surrounds two
      equal and symmetric spherical polar capsules (PC), 2.1+/-0.3 MUm in diameter,
      located at the same level. Each capsule contains a polar filament with five
      (rarely six) coils. The binucleate sporoplasm was irregular in shape, contained
      several sporoplasmosomes, ~175 nm in diameter and filled all the space of the two
      caudal appendages. Based on the arc shape of the spore with two tapering caudal
      appendages oriented to the basis of spores, on the number and position of the PC
      and of the polar filament coils and arrangements, and on the host specificity, we
      propose the name M. mylei n. sp. for this new myxozoan. Accordingly, this is the
      second described species of this genus.

PMID- 21895845
TI  - Perspective: physiological role(s) of the vascular myogenic response.
AB  - The vascular myogenic response is an inherent property of VSM in the walls of
      small arteries and arterioles, allowing these principal resistance segments of
      the microcirculation to respond to changes in transmural pressure. Elevated
      intraluminal pressure leads to myogenic constriction, whereas reduced pressure
      leads to myogenic dilation. This review focuses on the physiological significance
      of the myogenic response in microvascular networks. First, historical concepts
      related to the detection of stretch by the vessel wall are reviewed, including
      the wall tension hypothesis, and the implications of the proposal that the
      arteriolar network responds to Pp changes as a system of series-coupled myogenic
      effectors. Next, the role of the myogenic response in the local regulation of
      blood flow and/or Pc is examined. Finally, the interaction of myogenic
      constriction and dilation with other local control mechanisms, including
      metabolic, neural and shear-dependent mechanisms, is discussed. Throughout the
      review, an attempt is made to integrate historical and current literature with an
      emphasis on the physiological role, rather than the underlying signaling
      mechanisms, of this important component of vascular control.

PMID- 21895846
TI  - The prognostic role of quality of life assessment in breast cancer.
AB  - While the use of quality of life (QoL) assessments has been increasing in
      oncology, few studies have examined the prognostic significance of QoL in breast
      cancer. We investigated the association between QoL at presentation and survival
      in breast cancer. We examined 1,511 breast cancer patients treated at two single
      system cancer centers between January 2001 and December 2008. QoL was evaluated
      using the validated survey instrument EORTC-QLQ-C30. Patient survival was defined
      as the time interval between the date of first patient visit and the date of
      death from any cause/date of last contact. Univariate and multivariate Cox
      regression analyses were performed to evaluate the prognostic significance of QoL
      after controlling for the effects of age, tumor stage, and prior treatment
      history. Mean age at presentation was 52.5 years. There were 590 analytic and 921
      non-analytic patients. Patient stage of disease at diagnosis was I, 335; II, 591;
      III, 290; IV, 159; and 136 indeterminate. Median overall survival was 32.8 months
      (95% CI: 27.6-38.0). On univariate analysis, QoL function and symptom scales that
      were predictive of survival were physical (p < 0.001), role (p < 0.001),
      cognitive (p = 0.003), social (p < 0.001), fatigue (p < 0.001), nausea/vomiting
      (p < 0.001), pain (p < 0.001), dyspnea (p < 0.001), loss of appetite (p < 0.001),
      and constipation (p < 0.001). On multivariate analyses, only role function
      (degree of impairment of work and/or leisure/hobby related activities) was
      significantly associated with survival. This study suggests that baseline QoL (in
      particular, the role function) provides useful prognostic information in breast
      cancer.

PMID- 21895847
TI  - Nonmelanoma skin cancer chemoprevention.

PMID- 21895848
TI  - Topical antibiotic trends from 1993 to 2007: use of topical antibiotics for non
      evidence-based indications.
AB  - BACKGROUND: Systemic antibiotic use has become more conservative with the
      emergence of drug resistance. Topical antibiotics are employed for a variety of
      indications, although there are only a few evidence-based indications. OBJECTIVE:
      To examine topical antibiotics use in the outpatient setting. METHODS: Topical
      antibiotic use was characterized using data from the 1993 to 2007 National
      Ambulatory Medical Care Survey. Visits were identified at which a topical
      antibiotic was used and analyzed according to patient demographics, diagnoses,
      procedures, concomitant medications, and provider specialty. Topical antibiotic
      use over time was analyzed using linear regression. RESULTS: The most frequent
      diagnoses associated with topical antibiotic use were benign or malignant
      neoplasm of skin, impetigo, insect bite, and cellulitis. Data revealed a
      significant downward trend in topical antibiotics associated with dermatologic
      surgery (p<.001) and a nonsignificant downward trend in use in conjunction with
      skin biopsies (p=.09). Topical antibiotic use by dermatologists was noted to be
      decreasing over time, whereas among non dermatologists, it was noted to be
      increasing, although neither of these trends was statistically significant.
      CONCLUSION: Topical antibiotics continue to be used for non-evidence-based
      indications, despite data that suggest that such use may be detrimental for
      patients and represents significant costs to the health care system. The authors
      have indicated no significant interest with commercial supporters.

PMID- 21895849
TI  - Role of podoplanin expression in esophageal squamous cell carcinoma: a
      retrospective study.
AB  - Lymphatic metastasis is the predominant cause of the low overall survival of
      patients with esophageal squamous cell carcinoma (ESCC), as there are no faithful
      methods available predicting early metastasis. Recent studies suggest an effect
      of podoplanin expression on metastatic spreading to lymph nodes. The purpose of
      this study was to investigate the influence of podoplanin expression on lymphatic
      metastasis and tumor cells, and to find the relationship between podoplanin
      expression and prognosis of patients with ESCC. We evaluated the level of
      podoplanin expression on tumor cells and the lymphatic vessel density change of
      tumor mass compared with normal tissue from the same patient through D2-40
      immunohistochemistry staining, and analyzed associations between these two
      variables and various clinicopathologic parameters individually or conjunctively.
      There was an association between podoplanin expression and the frequency of lymph
      node metastases. In 45 patients (80%), podoplanin was expressed on the tumor
      cells. Twenty-one patients (37.5%) showed high levels of expression. The 5-year
      disease-free survival rate (5%) for patients with high levels of podoplanin
      expression was significantly lower (P < 0.001) than for patients with low and
      moderate expression of podoplanin (54% and 27%, respectively). We concluded that
      podoplanin is expressed frequently in ESCC, and that the expression of podoplanin
      on cancer cells, lymphatics, or both is correlated with lymphatic metastasis and
      clinical outcome.

PMID- 21895850
TI  - Influence of the esophageal hiatus size on the lower esophageal sphincter, on
      reflux activity and on symptomatology.
AB  - Hiatal hernia is an underlying factor contributing to gastroesophageal reflux
      disease (GERD). However, it remains elusive whether the size of the esophageal
      hiatus has a de facto influence on the lower esophageal sphincter (LES), on the
      intensity of patient reflux, on GERD symptoms and on the quality of life (QoL).
      One hundred patients with documented chronic GERD underwent laparoscopic
      fundoplication. QoL was evaluated before surgery using the Gastrointestinal
      Quality of Life Index (GIQLI). Additionally, GERD symptoms and nonspecific
      gastrointestinal symptoms were documented using a standardized questionnaire
      (score 0-224). The size of the esophageal hiatus was measured during surgery by
      calculating the hiatal surface area (HSA). Correlation analysis between the
      preoperative QoL, GERD symptoms, esophageal manometry, multichannel intraluminal
      impedance monitoring data and HSA size was performed, in order to investigate
      whether the HSA has an influence on the patients'symptoms, GIQLI, manometry and
      multichannel intraluminal impedance monitoring data. Statistical significance was
      set at a P-value of 0.05. The HSA sizes ranged from 1.51cm(2) to 16.09cm(2) (mean
      4.14cm(2) ). The preoperative GIQLI ranged from 15 points to 133 points (mean
      94.37 points). Symptom scores ranged from 2 points to 192 points (mean 49.84
      points). No significant influence of the HSA on GIQLI or preoperative symptoms
      was recorded. HSA size had a significant negative effect on LES pressure.
      Additionally, there was a significant positive correlation between HSA size and
      number of refluxes in supine position. For the rest of the evaluated data,
      including DeMeester score, total number of refluxes, refluxes in upright
      position, acid reflux events, proximal reflux events, LES length and body
      motility, no significant correlation was found. Although patients subjectively
      are not significantly affected by the size of the hiatus, it has significant
      effects on the LES pressure and on gastroesopageal reflux in supine position.

PMID- 21895851
TI  - Outcomes of endoscopic and surgical resection for a second primary cancer in the
      residual cervical esophagus after thoracic esophagectomy.
AB  - Patients who have received subtotal esophagectomy for thoracic esophageal cancer
      must be closely monitored for second primary malignancies. The purpose of this
      study is to review and assess patients who developed a second primary esophageal
      cancer in the residual cervical esophagus. Between 1996 and 2010, 10 patients
      were diagnosed in our hospital with esophageal squamous cell cancer in the
      residual cervical esophagus after undergoing thoracic esophagectomy and were
      treated with endoscopic or surgical resection. Data from these patients were
      reviewed retrospectively. Seven of the 10 patients (70%) had multiple primary
      carcinoma lesions at the time of their esophagectomy. A second primary cancer in
      the residual cervical esophagus was detected in eight patients during follow-up
      endoscopic examinations while the patients were still asymptomatic. Seven of the
      patients underwent endoscopic resection for a superficial cancer. None of those
      patients experienced any complications, and all are currently alive and cancer
      free. The remaining three patients underwent resection of the cervical esophagus
      with regional lymph node dissection. Two of those patients experienced severe
      complications; one subsequently died (hospital death) from pneumonia, 12 months
      after surgery, while the other died from recurrence of his cancer. The third
      patient is alive and cancer-free. Early detection of a second primary malignancy
      in the residual cervical esophagus followed by endoscopic resection is the best
      treatment strategy for patients who previously received subtotal esophagectomy
      for thoracic esophageal cancer. Surgical resection puts patients at high risk of
      mortality or morbidity.

PMID- 21895852
TI  - Recent advancement of observing living cells in the esophagus using CM double
      staining: endocytoscopic atypia classification.
AB  - Magnification endoscopy enables in vivo evaluation of gastrointestinal mucosa.
      Furthermore, endocytoscopy (ECS) with ultra-high magnification enables in vivo
      observation of cellular atypia during routine endoscopic examination. The purpose
      of this study is to clarify the efficacy of ECS and endocytoscopic atypia (ECA)
      classification in various types of benign and malignant pathology in the
      esophagus. Consecutive 110 patients, who underwent ECS in our institution from
      March 2003 to December 2009, were included in this study. One hundred and forty
      six esophageal lesions were classified according to ECA classification, and these
      endocytoscopic images were compared with histological images. We categorized
      endocytoscopic images into five categories according to size and uniformity of
      nuclei, number of cells and regularity of cellular arrangement. Eighty-one out of
      89 ECA-1 to ECA-3 lesions (91.0%) corresponded to Vienna categories 1 to 3.
      Seventy-one out of 84 ECA-4 or ECA-5 lesions (91.2%) corresponded to Vienna
      category 4 or 5. Overall accuracy of ECS was 91.3%, providing images similar to
      conventional hematoxylin and eosin staining. In addition, with ECS, we can take
      an 'optical biopsy' even in patients with cardiovascular disease without
      interrupting anticoagulant therapy. A newly designed single charge-coupled device
      endocytoscope allows observation of target tissue noninvasibly from regular
      magnification to ultra-high magnification. The development of ECS has opened the
      door to in vivo cellular imaging, enabling endoscopic diagnosis of tissue
      cytological atypia during routine endoscopic examination.

PMID- 21895853
TI  - Higher importance of interleukin 6 than classic tumor markers (carcinoembryonic
      antigen and squamous cell cancer antigen) in the diagnosis of esophageal cancer
      patients.
AB  - It has been suggested that interleukin 6 (IL-6) plays a potential role in the
      growth and progression of tumors, including esophageal cancer (EC). The aim of
      the study was to compare clinical significance of serum IL-6 with classic tumor
      markers - carcinoembryonic antigen (CEA) and squamous cell cancer antigen (SCC
      Ag) - in EC patients in relation to its histological types - squamous cell
      carcinoma of esophagus (ESCC) and adenocarcinoma (AD) of esophagus. The study
      included 53 EC patients and 90 healthy subjects. Serum IL-6 and CEA levels were
      determined using immunoenzyme assays, while SCC-Ag - chemiluminescent assay. The
      diagnostic criteria and prognostic values for markers were defined. The levels of
      all proteins tested in EC, ESCC, and AD were higher than in healthy subjects. The
      percentage of elevated results was substantially higher for IL-6 (86%) than for
      CEA (30%) and SCC-Ag (24%) in EC, similarly as in ESCC (87%, 23%, and 33%) and AD
      (87%, 39%, and 13%, respectively) patients. Concentrations of IL-6 depended on
      distant metastases and patients' survival in EC and were significantly higher in
      ESCC patients with more advanced tumor stage and nodal metastases. The IL-6 area
      under receiver operating characteristic curve (0.92) was larger than for CEA
      (0.84) and SCC-Ag (0.62) in EC, likewise in ESCC (0.92, 0.87, 0.77) and AD (0.91,
      0.79, 0.57, respectively). Our findings indicate better usefulness of IL-6 than
      classic tumor markers in the diagnosis of EC, especially in patients with ESCC.

PMID- 21895855
TI  - Benefits of regional anesthesia in children.

PMID- 21895854
TI  - Criteria for assessing operating room utilization in a free-standing children's
      hospital.
AB  - BACKGROUND:   The staffed hours of operation in any surgical facility are a
      valuable institutional resource. The realistic target for the utilization of this
      resource is dependent on many factors including scheduling, efficiency, and
      culture of the facility. There is no previously reported measure for the actual
      utilization of staffed regular operating room (OR) hours in an academic pediatric
      institution. The leadership of the perioperative services at Children's Hospital
      Boston (CHB) sought to define the utilization of surgical suite staffed block
      time hours at that institution and in addition determine whether changes in
      workflow could increase the measured utilization. METHODS:   Operating room
      efficiency in fiscal year 2009 was measured using two variables: utilization and
      turnover measured in hours for each month in fiscal year 2009, recorded in hours
      expressed as ratios (observed/expected) and as differences (observed - expected).
      A total of 27,851 cases from October 1, 2008, through September 30, 2009, were
      analyzed. All elective cases were scheduled electronically following
      institutional guidelines; urgent or emergent procedures were scheduled into
      vacant time slots on the day of the procedure. Time series analysis based on a
      generalized autoregressive moving average process was used to compare expected
      with observed utilization and to evaluate changes in utilization and turnover
      ratios. RESULTS:   Efficiency as measured by capped utilization divided by total
      available time in the OR averaged 79%. Utilization ratios ranged from a low of
      73% in February 2009 to a high of 87% in July 2009. An improvement in on-time
      first-case starts may have contributed to the increase in the utilization of
      staffed block time. Turnover time as defined by turnover ratio decreased
      significantly over time, indicating an improved efficiency in the OR starting in
      April 2009. CONCLUSIONS:   Adhering to the specific guidelines that are followed
      at CHB, the mean utilization of scheduled block time was 79%. This was achieved
      by maximizing workflow in the surgical, anesthesia, and nursing disciplines to
      shorten turnover time, fill gaps in the elective schedule with emergency
      procedures, and provide staffing to accommodate cases that extend beyond the
      scheduled staffed time prior to the reporting period. Simulated models from other
      pediatric institutions suggest that the optimal utilization of designated time
      periods in a surgical facility may range from 85% to 90%.

PMID- 21895856
TI  - Lymphogranuloma venereum variant L2b-specific polymerase chain reaction:
      insertion used to close an epidemiological gap.
AB  - The management of the ongoing lymphogranuloma venereum epidemic in industrialized
      Western countries caused by Chlamydia trachomatis variant L2b still needs
      improvements in diagnosis, therapy and prevention. We therefore developed the
      first rapid C. trachomatis variant L2b-specific polymerase chain reaction to
      circumvent laborious ompA gene sequencing.

PMID- 21895857
TI  - Liposomal amphotericin B twice weekly as antifungal prophylaxis in paediatric
      haematological malignancy patients.
AB  - Data on antifungal prophylaxis in paediatric cancer patients at high risk for
      invasive fungal disease (IFD) are scant. Intermittent administration of liposomal
      amphotericin B (LAMB) has been shown to be safe and effective in adult patients
      with haematological malignancies. We prospectively evaluated the safety and
      efficacy of prophylactic LAMB at a dosage of 2.5 mg/kg twice weekly in children
      at high risk for IFD. Efficacy was compared with that in a historical control
      group of patients with similar demographic characteristics not receiving LAMB
      prophylaxis. A total of 46 high-risk patients (24 boys; mean age, 7.7 years) with
      187 episodes of antifungal prophylaxis were analysed. The median duration of
      neutropenia (<500/MUL) was 10 days. LAMB was discontinued in four patients
      because of acute allergic reactions. Median values for creatinine and liver
      enzymes at end of treatment did not differ significantly from those at baseline.
      Hypokalaemia (<3.0 mmol/L) occurred with 13.5% of the prophylactic episodes, but
      was usually mild and always reversible. No proven/probable IFD occurred in
      patients receiving LAMB prophylaxis. In comparison, five proven and two probable
      IFDs were observed in 45 historical controls not receiving LAMB prophylaxis (p
      0.01). LAMB prophylaxis had no impact on the use of empirical antifungal therapy.
      Systemic antifungal prophylaxis with LAMB 2.5 mg/kg twice weekly is feasible and
      safe, and seems to be an effective approach for antifungal prophylaxis in high
      risk paediatric cancer patients.

PMID- 21895858
TI  - Clinical and microbiological features of bacteraemia with Aerococcus urinae.
AB  - Aerococcus urinae is a Gram-positive bacterium that can cause invasive infection,
      including infectious endocarditis (IE), mainly in older men. A. urinae is often
      misclassified in routine diagnostic laboratories. Through searches in the
      laboratory databases we identify 16 isolates of A. urinae causing bacteraemia
      during a 6-year period in southern Sweden, indicating that bacteraemia with A.
      urinae occurs in at least three cases per million inhabitants per year. The
      identity of isolates was confirmed by sequencing of the 16S rRNA genes and
      antibiotic susceptibility testing identified two ciprofloxacin-resistant
      isolates. A. urinae was the only significant pathogen isolated in all cases.
      Fifteen of the 16 patients were male, 15/16 were more than 70 years old, and
      12/16 had underlying urological conditions. Though a urinary tract focus was
      suspected in the majority of cases, the bacterium was rarely found in urinary
      samples. Nine patients fulfilled the criteria for severe sepsis and an additional
      four fulfilled the criteria for sepsis. Only one fatality was recorded. Patients
      were treated mainly with beta-lactam antibiotics but fluoroquinolones and
      clindamycin were also used. Three cases of IE were diagnosed and these were
      complicated by spondylodiscitis in one case and by septic embolization to the
      brain in one case. An increased awareness of A. urinae is crucial to establishing
      its role as an important pathogen in older men with urinary tract disease.

PMID- 21895859
TI  - Paroxetine controlled-release formulation in the treatment of major depressive
      disorder: a randomized, double-blind, placebo-controlled study in Japan and
      Korea.
AB  - AIM: The main purpose of this study was to evaluate the efficacy of paroxetine
      controlled-release (CR) formulation compared to placebo. A secondary objective
      was to test the hypothesis that the CR decreases selective-serotonin-reuptake
      inhibitors-induced nausea as its formulation allows more distal gastrointestinal
      absorption than the paroxetine immediate-release (IR) formulation. METHODS: We
      conducted this study in Japanese and Korean patients with major depressive
      disorder (MDD) in order to demonstrate the efficacy and safety of paroxetine CR
      compared with placebo. The primary efficacy end-point was the adjusted mean
      change from baseline in the 17-item Hamilton Rating Scale for Depression total
      score at Week 8. RESULTS: A total of 416 patients with MDD were randomly assigned
      to the CR, IR and placebo groups. The mean change from baseline in the 17-item
      Hamilton Rating Scale for Depression was -12.8 in the CR group, -12.5 in the IR
      group, and -10.4 in the placebo group, which showed a statistically significant
      difference compared to placebo in CR (P < 0.001) and IR (P = 0.015). The
      incidence of adverse events was 65% in CR, 69% in IR and 55% in placebo. The
      adverse events were mostly mild or moderate in severity. In the early treatment
      period, when initiated from 12.5 mg, the incidence of nausea in the CR group was
      6%, which was comparable with that of placebo (5%). CONCLUSION: Paroxetine CR is
      efficacious in the acute treatment of MDD and may have the potential benefit of
      decreasing the incidence of nausea in the early treatment period.

PMID- 21895860
TI  - Serum cortisol and dehydroepiandrosterone-sulfate levels in schizophrenic
      patients and their first-degree relatives.
AB  - AIMS: Alterations in cortisol and dehydroepiandrosterone sulfate (DHEA-S) levels
      are thought to play a role in the pathophysiology of neuropsychiatric disorders,
      including schizophrenia. The aim of this study was to investigate the role of
      serum cortisol and DHEA-S in the pathophysiology of schizophrenia. METHODS: Sixty
      schizophrenic patients, 70 healthy first-degree relatives, and 60 healthy
      volunteers were included. Sociodemographic characteristics, data regarding
      disease duration and severity, as well as ongoing and previous drug use were
      recorded. Serum cortisol and DHEA-S levels were measured. RESULTS: Serum cortisol
      and DHEA-S levels were significantly higher in the schizophrenia group compared
      with the first-degree relatives and controls (P < 0.05). Serum cortisol levels in
      the first-degree relatives were significantly higher than in the healthy controls
      (P < 0.05). There was no significant difference between the first-degree
      relatives and healthy-controls in terms of DHEA-S levels and between the three
      groups in terms of serum cortisol/DHEA-S ratios. CONCLUSIONS: Elevated serum
      cortisol levels in schizophrenic patients might be associated with the role of
      cortisol in the pathophysiology of schizophrenia. Also, the elevation of serum
      cortisol levels in first-degree relatives compared to controls suggests that
      similar pathophysiological processes might have a role in individuals without any
      disease symptoms, but with a genetic predisposition for schizophrenia. Elevated
      serum DHEA-S levels might be the result of a compensatory response to elevated
      cortisol levels. Serum cortisol and DHEA-S levels may be used as a biological
      marker for the diagnosis of schizophrenia; however, further studies with larger
      sample sizes are warranted to support this finding.

PMID- 21895862
TI  - Novel molecular imaging in lung and pleural diseases.
AB  - Molecular imaging provides an opportunity to study biological processes in vivo.
      Specific molecular 'probes' are labelled with radioactive tracers, and imaging is
      carried out using either PET or gamma-cameras. The imaging is quantitative, and
      therefore the activity of a specific biological process (e.g. metabolism or
      proliferation) can be numerically assessed, which may be important for prognosis
      or therapy monitoring. The use of molecular imaging may lead to the development
      of a 'molecular profile' of a disease, therefore facilitating individualization
      of therapy and rational treatment approaches. This review article summarizes the
      most commonly used molecular imaging agents and their role in lung and pleural
      diseases. This is a rapidly developing field as new targets and imaging probes
      are being developed and as their clinical roles are being established.

PMID- 21895863
TI  - Laboratory diagnosis of pertussis: agglutination is not suitable.

PMID- 21895864
TI  - Economic burden of injuries in children: cohort study based on administrative
      data in a northwestern Italian region.
AB  - BACKGROUND: The aims of the present study were to identify which types of
      injuries are responsible for the major component of the health burden and to
      estimate the relative costs in a cohort of Italian children. METHODS: All
      children (0-14 years) residing in the Piedmont region, who were hospitalized for
      an injury (ICD-9-CM codes 800-995, excluding late effects from injury and
      allergies) between 1 January 2003 and 31 December 2003, were considered. The
      cohort was linked by a unique identifier to: all the hospitalizations, all the
      day-hospital care, and all the prescribed medicines. Outcome was defined as the
      difference in health service use in the 12 months following the injury, and was
      compared to the year preceding the injury occurrence. Total number of hospital
      admissions for each individual, cumulative length of stay, day-hospital care, and
      prescribed medicines were calculated for the two periods. The cost of additional
      inpatient days and of additional outpatient care was calculated. RESULTS: The
      three most common injury categories were: intracranial injury (27.6%), fracture
      of upper limb (18.7%); and fracture of lower limb (9.07%); they were responsible
      for the major part of the additional inpatient days (55%) and outpatient care
      (70%). The additional expense for the National Health System during the year
      following an injury is approximately 1700 ? for children aged 0-14. CONCLUSIONS:
      This is the first Italian study to attempt to quantify the injury economic burden
      in a cohort of children: the costs imposed on society by injuries, suggest how
      important it is to commit resources to injury prevention.

PMID- 21895865
TI  - Effect of neonatal resuscitation courses on long-term neurodevelopmental outcomes
      of newborn infants with perinatal asphyxia.
AB  - BACKGROUND: In previous studies, it has been demonstrated that Neonatal
      Resuscitation Program (NRP) courses improve the early outcomes of infants with
      perinatal asphyxia, but there has been no evidence to demonstrate the effect of
      NRP on long-term outcomes of perinatal asphyxia. The goal of the present study
      was to determine the effect of NRP courses on the long-term neurodevelopmental
      outcome of perinatal asphyxia. METHODS: This prospective study included infants
      referred to the Neonatal Unit during the years 2003-2005. Those patients who were
      referred before NRP courses (pretraining period) were designated as group 1,
      those who were referred after the first NRP course (transition period) as group
      2, and those who were referred after the second NRP course (post-training period)
      as group 3. Neurodevelopmental outcomes were assessed and compared at 4-6 years
      of age. RESULTS: The study involved 40 patients: 23 in group 1, nine in group 2
      and eight in group 3. The number of patients who had been diagnosed with cerebral
      palsy was 13 in group 1, two in group 2, and one in group 3, which was a
      significant decrease. The number of patients with seizures and
      electroencephalography abnormality was 12 and 14 in group 1, three and two in
      group 2, and one and one in group 3, respectively, which was also a significant
      decrease. CONCLUSIONS: NRP courses have positive effects on short-term as well as
      long-term neurodevelopmental outcomes of infants with perinatal asphyxia. Further
      studies are required to determine the effects of NRP courses on minor deficits,
      such as cognitive and behavioral disturbances.

PMID- 21895867
TI  - Membrane sialidase NEU3 is highly expressed in human melanoma cells promoting
      cell growth with minimal changes in the composition of gangliosides.
AB  - NEU3 is a membrane sialidase specific for gangliosides. Its increased expression
      and implication in some cancers have been reported. Here, we analyzed NEU3
      expression in malignant melanoma cell lines and its roles in the cancer
      phenotypes. Quantitative RT-PCR revealed that high levels of the NEU3 gene were
      expressed at almost equivalent levels with those in colon cancers. To examine the
      effects of overexpression of NEU3, NEU3 cDNA-transfectant cells were established
      using a melanoma cell line SK-MEL-28 and its mutant N1 lacking GD3. SK-MEL-28
      sublines overexpressing both the NEU3 gene and NEU3 enzyme activity showed no
      changes in both cell growth and ganglioside expression, while N1 cells showed a
      mild increase in cell proliferation with increased phosphorylation of the EGF
      receptor and neo-synthesis of Gb3 after NEU3 transfection. In contrast, NEU3
      silencing resulted in a definite reduction in cell growth in a melanoma line
      MeWo, while ganglioside patterns underwent minimal changes. Phosphorylation
      levels of ERK1/2 with serum stimulation decreased in the NEU3-silenced cells. All
      these results suggest that NEU3 is highly expressed to enhance malignant
      phenotypes including apoptosis inhibition in malignant melanomas.

PMID- 21895866
TI  - Ampicillin versus penicillin in the empiric therapy of extremely low-birthweight
      neonates at risk of early onset sepsis.
AB  - BACKGROUND: There are no comparative data on the impact of different empiric
      antibiotic regimens on early bowel colonization as well as on clinical efficacy
      in extremely low-birthweight (ELBW) neonates at risk of early onset sepsis (EOS).
      METHODS: A subgroup analysis was carried out of ELBW neonates recruited into a
      two-center, prospective, cluster randomized study comparing ampicillin and
      penicillin both combined with gentamicin, within the first 72 h of life. A
      composite primary end-point (need for change of antibiotics within 72 h and/or 7
      day all-cause mortality) and the rate and duration of colonization by
      opportunistic aerobic microorganisms were assessed using hierarchical models
      corrected for study center and period. RESULTS: In the ampicillin (n= 36) and
      penicillin (n= 39) groups change of antibiotics, 7 day mortality and the
      composite end-point occurred at similar rates. Neonatal intensive care unit
      mortality for infants with gestational age <26 weeks was lower in the ampicillin
      group. Ampicillin treatment was associated with a higher colonization rate by
      Klebsiella pneumoniae, including ampicillin-resistant strains. CONCLUSION:
      Preliminary data indicate an urgent need for adequately powered studies of early
      antibiotic therapy in the subpopulation of ELBW neonates at risk of EOS.

PMID- 21895868
TI  - Asbestos surface provides a niche for oxidative modification.
AB  - Asbestos is a potent carcinogen associated with increased risks of malignant
      mesothelioma and lung cancer in humans. Although the mechanism of carcinogenesis
      remains elusive, the physicochemical characteristics of asbestos play a role in
      the progression of asbestos-induced diseases. Among these characteristics, a high
      capacity to adsorb and accommodate biomolecules on its abundant surface area has
      been linked to cellular and genetic toxicity. Several previous studies identified
      asbestos-interacting proteins. Here, with the use of matrix-assisted laser
      desorption ionization-time of flight mass spectrometry, we systematically
      identified proteins from various lysates that adsorbed to the surface of
      commercially used asbestos and classified them into the following groups:
      chromatin/nucleotide/RNA-binding proteins, ribosomal proteins, cytoprotective
      proteins, cytoskeleton-associated proteins, histones and hemoglobin. The surfaces
      of crocidolite and amosite, two iron-rich types of asbestos, caused more protein
      scissions and oxidative modifications than that of chrysotile by in situ
      generated 4-hydroxy-2-nonenal. In contrast, we confirmed the intense hemolytic
      activity of chrysotile and found that hemoglobin attached to chrysotile, but not
      silica, can work as a catalyst to induce oxidative DNA damage. This process
      generates 8-hydroxy-2'-deoxyguanosine and thus corroborates the involvement of
      iron in the carcinogenicity of chrysotile. This evidence demonstrates that all
      three types of asbestos adsorb DNA and specific proteins, providing a niche for
      oxidative modification via catalytic iron. Therefore, considering the affinity of
      asbestos for histones/DNA and the internalization of asbestos into mesothelial
      cells, our results suggest a novel hypothetical mechanism causing genetic
      alterations during asbestos-induced carcinogenesis.

PMID- 21895869
TI  - Correlation between mammographic findings and corresponding histopathology:
      potential predictors for biological characteristics of breast diseases.
AB  - The present study retrospectively evaluated the mammographic findings of 606
      Japanese women with breast cancer (median age 50 years; range 27-89 years) and
      correlated them with histopathological characteristics. Mammographic findings
      were evaluated with an emphasis on mass shape, margin, density, calcification,
      and the presence of architectural distortion; these findings were correlated with
      histopathological characteristics such as intrinsic subtype, histological grade,
      lymphovascular invasion, and the Ki-67 labeling index. An irregular mass shape
      and masses with a spiculated margin were significantly higher in the group of
      patients with luminal A breast cancer than in patients with masses that were
      lobular or round, or in tumors with an indistinct or microlobulated periphery (P
      = 0.017, P = 0.024, P < 0.001, and P = 0.001, respectively). Irregular mass shape
      and spiculated periphery were significantly lower in patients with Grade 3 cancer
      (P < 0.001 for both). In terms of lymphovascular invasion, there were significant
      differences between oval and irregular or round mass shape (P = 0.008 and P =
      0.034), between tumors with a microlobulated and indistinct periphery (P =
      0.014), between tumors with a punctate and amorphous or pleomorphic calcification
      shape (P = 0.030 and 0.038), and between the presence and absence of
      architectural distortion (P = 0.027). Equivalent or low-density masses were also
      higher in Grade 1 breast cancers (P = 0.007). There were significant differences
      in the Ki-67 labeling index between irregular and lobular or round tumors (P <
      0.001 and P = 0.014), as well as between spiculated and indistinct or
      microlobulated tumors (P < 0.001 for both). Significant differences were noted in
      the mammographic features of different primary breast cancer subtypes. These
      proposed mammographic diagnostic criteria based on biological characteristics may
      contribute to a more accurate prediction of biological behavior of breast
      malignancies.

PMID- 21895870
TI  - Rab5A is associated with axillary lymph node metastasis in breast cancer
      patients.
AB  - The expression of Rab proteins has been associated with cancer. However, few data
      are available on Rab5A expression in human breast cancer or its impact on disease
      progression. First, we examined the functional role of Rab5A in breast cancer
      cells. The expression of Rab5A in MDA-MB-231 cells can be stimulated by epidermal
      growth factor in a dose-dependent manner. The epidermal growth factor-induced
      increase of Rab5A expression correlated well with enhanced migration in wound
      healing migration assays in these cells. Furthermore, we evaluated the expression
      of Rab5A in breast cancer specimens using immunohistochemical staining, then
      analyzed the relationship between the expression of Rab5A and clinicopathological
      parameters. The increased expression of Rab5A protein in 123 breast cancer
      samples was associated with higher histological grade (P = 0.004), more
      lymphovascular invasion (P = 0.027), more axillary lymph node (LN) metastasis (P
      = 0.008), and a higher number of axillary LN metastases (P = 0.043). Among 218
      axillary LNs of more than 10 breast cancer patients with node metastases, 167
      metastatic LNs were found to have increased Rab5A expression. Rab5A is associated
      with axillary LN metastasis in breast cancer patients.

PMID- 21895873
TI  - Retracted: Modulation of p53 /Akt / phosphatase and tensin homolog expression by
      esculetin potentiates the anticancer activity of cisplatin and prevents its
      nephrotoxicity.

PMID- 21895871
TI  - Who participates in the gastric cancer screening and on-time rescreening in the
      National Cancer Screening Program? A population-based study in Korea.
AB  - Gastric cancer (GC) screening is a major challenge in countries where the disease
      is highly prevalent. This study was conducted to identify the factors associated
      with participation in GC screening and on-time rescreening among the average-risk
      population in Korea. The study population was derived from the National Cancer
      Screening Program database. The population for this study was 22 913 618
      individuals aged >=40 years who had been invited to participate in a GC screening
      program from 2005 to 2006. We determined whether these individuals had attended
      the GC screening program and which method - an upper gastrointestinal series
      (UGIS) or endoscopy-they underwent. We followed the participants to determine
      whether they had a second GC screening after 2 years. The overall participation
      rate in the GC screening was 20.5%. More people underwent UGIS than endoscopy.
      Individuals who had been screened by endoscopy rather than UGIS were more likely
      to be younger, male, or those who were National Health Insurance (NHI)
      beneficiaries with a higher premium rate. Of those who underwent baseline
      screening, 59.4% participated in a rescreening program 2 years later. NHI
      beneficiaries with a higher premium rate were significantly more likely to be
      rescreened than medical aid recipients. The results from this study showed that
      the UGIS were more commonly used in organized GC screenings in Korea, and those
      who underwent UGIS were more likely to return for subsequent screening compared
      to those who underwent an endoscopy.

PMID- 21895872
TI  - MiR-195, miR-196b, miR-181c, miR-21 expression levels and O-6-methylguanine-DNA
      methyltransferase methylation status are associated with clinical outcome in
      glioblastoma patients.
AB  - Glioblastoma multiforme (GBM) is the most frequently occurring primary malignant
      brain tumor; patients with GBM often have a very poor prognosis and differing
      responses to treatment. Therefore, it is very important to find new biomarkers
      that can predict clinical outcomes and help in treatment decisions. MicroRNAs are
      small, non-coding RNAs that function as post-transcriptional regulators of gene
      expression and play a key role in the pathogenesis of GBM. In a group of 38
      patients with primary GBM, we analyzed the expression of eight microRNAs (miR-21,
      miR-128a, miR-181c, miR-195, miR-196a, miR-196b, miR-221, and miR-222). In
      addition, we examined the methylation status of O-6-methylguanine-DNA
      methyltransferase (MGMT) promoter by high-resolution melting analysis, as this
      has been shown to be a predictive marker in GBM. MGMT methylation status
      correlated with progression-free survival (P = 0.0201; log-rank test) as well as
      with overall survival (P = 0.0054; log-rank test). MiR-195 (P = 0.0124; log-rank
      test) and miR-196b (P = 0.0492; log-rank test) positively correlated with overall
      survival. Evaluation of miR-181c in combination with miR-21 predicted time to
      progression within 6 months of diagnosis with 92% sensitivity and 81% specificity
      (P < 0.0001). Our data confirmed that the methylation status of MGMT but also miR
      21, miR-181c, miR-195, and miR-196b to be associated with survival of GBM
      patients. Above all, we suggest that the combination of miR-181c and miR-21 could
      be a very sensitive and specific test to identify patients at high risk of early
      progression after surgery.

PMID- 21895875
TI  - Genetically engineered humanized anti-ganglioside GM2 antibody against multiple
      organ metastasis produced by GM2-expressing small-cell lung cancer cells.
AB  - Small-cell lung cancer (SCLC) grows rapidly and metastasizes to multiple organs.
      We examined the antimetastatic effects of the humanized anti-ganglioside GM2
      (GM2) antibodies, BIW-8962 and KM8927, compared with the chimeric antibody KM966,
      in a SCID mouse model of multiple organ metastases induced by GM2-expressing SCLC
      cells. BIW-8962 and KM8927 induced higher antibody-dependent cellular
      cytotoxicity and complement-dependent cytotoxicity than KM966 against the GM2
      expressing SCLC cell line SBC-3 in vitro. These humanized antibodies inhibited
      the production of multiple organ metastases, increased the number of apoptotic
      cells, and prolonged the survival of the SCID mice. Histological analyses using
      clinical specimens showed that SCLC cells expressed GM2. These findings suggest
      that humanized anti-GM2 antibodies could be therapeutically useful for
      controlling multiple organ metastases of GM2-expressing SCLC.

PMID- 21895874
TI  - GSK962040: a small molecule motilin receptor agonist which increases
      gastrointestinal motility in conscious dogs.
AB  - BACKGROUND: GSK962040, a small molecule motilin receptor agonist, was identified
      to address the need for a safe, efficacious gastric prokinetic agent. However, as
      laboratory rodents lack a functional motilin system, studies in vivo have been
      limited to a single dose, which increased defecation in rabbits. Motilin agonists
      do not usually increase human colonic motility, so gastric prokinetic activity
      needs to be demonstrated. METHODS: The effect of intravenous GSK962040 on gastro
      duodenal motility was assessed in fasted dogs implanted with strain gauges.
      Activity was correlated with blood plasma concentrations of GSK962040 (measured
      by HPLC-MS/MS) and potency of GSK962040 at the dog recombinant receptor [using a
      Fluorometric Imaging Plate Reader (Molecular Devices, Wokingham, UK) after
      expression in HEK293 cells]. KEY RESULTS: GSK962040 activated the dog motilin
      receptor (pEC(50) 5.79; intrinsic activity 0.72, compared with [Nle(13) ]
      motilin). In vivo, GSK962040 induced phasic contractions, the duration of which
      was dose-related (48 and 173 min for 3 and 6 mg kg(-1) ), driven by mean plasma
      concentrations >1.14 MUmol L(-1) . After the effects of GSK962040 faded,
      migrating motor complex (MMC) activity returned. Migrating motor complex
      restoration was unaffected by 3 mg kg(-1) GSK962040 but at 6 mg kg(-1) , MMCs
      returned 253 min after dosing, compared with 101 min after saline (n=5 each).
      CONCLUSIONS & INFERENCES: The results are consistent with lower potency for
      agonists at the dog motilin receptor, compared with humans. They also define the
      doses of GSK962040 which stimulate gastric motility. Correlation of in vivo and
      in vitro data in the same species, together with plasma concentrations, guides
      further studies and translation to other species.

PMID- 21895876
TI  - Optical clearing improves the imaging depth and signal-to-noise ratio for digital
      analysis and three-dimensional projection of the human enteric nervous system.
AB  - BACKGROUND: Due to the dispersed nature of neurites and fibers, the microtome
      based 2-dimensional histology provides only a limited perspective of the enteric
      nervous system. To visualize the enteric plexus, we applied optical clearing to
      avoid scattering in the human ileum to facilitate photon penetration for 3
      dimensional (3-D) microscopy of the neural tissue. METHODS: Human ileal specimens
      were derived by trimming the donor bowel due to its excess length during the
      clinical trial of small intestinal transplantation. The pan-neuronal marker
      PGP9.5 was used as the immunostaining target to reveal the enteric plexuses. The
      labeled tissues were immersed in the optical-clearing solution prior to deep
      tissue confocal microscopy. The serial sections were digitally analyzed and
      processed by reconstruction algorithms for 3-D visualization. KEY RESULTS:
      Optical clearing of the ileal specimen led to less fluorescence signal decay
      along the focal path in the tissue and a higher signal-to-noise ratio of the
      confocal micrographs in comparison with the untreated saline control. Taking
      advantage of the high signal-to-noise ratio images, we applied software-based
      signal analysis to identify the presence of the nerve fibers and quantify the
      signal peaks. The image stacks derived from the serial anatomic micrographs
      created panoramic views of the gut wall innervations with their associated
      microstructures. CONCLUSIONS & INFERENCES: We provide an optical approach to
      improve the imaging depth in 3-D neurohistology of the human ileum. This
      methodology has significant promise in facilitating our understanding of the
      enteric nervous system in health and disease.

PMID- 21895879
TI  - MRI-based intravenous thrombolysis in stroke patients with unknown time of
      symptom onset.
AB  - BACKGROUND: Currently, stroke patients with unknown time of symptom onset (UTOS)
      are excluded from therapy with intravenous tissue Plasminogen Activator. We
      hypothesized that MRI-based intravenous thrombolysis is safe in UTOS. METHODS: We
      analyzed radiological and clinical data as well as outcomes of stroke patients
      (including UTOS) who received intravenous thrombolytic therapy after MRI.
      RESULTS: Compared to patients with known time of symptom onset (n=131), UTOS
      (n=17) were older (81, 71-88 vs. 75 years, 66-82, P=0.03), had a longer median
      time between last-seen-well and thrombolysis (12.3 h, IQR 11.5-15.2 h vs. 2.1 h,
      1.8-2.8 h, P<0.01), had a longer median door-to-needle time (86 min, 49-112 vs.
      60 min, 49-76, P=0.02), and a higher rate of arterial obstruction on MR
      angiography (82.4% vs. 56.5%, P=0.04). No symptomatic intracerebral hemorrhage
      occurred in UTOS. After 3 months, there was no significant difference between
      groups concerning good functional outcome (modified Rankin Scale 0-2; 35.3% vs.
      49.6%, P=0.26) or mortality (0% vs. 15.3%, P=0.08). In multivariate analyses
      including age, gender, baseline NIHSS, and atrial fibrillation UTOS did not have
      an independent effect on good functional outcome after 3 months (OR 1.16; 0.32
      4.12, P=0.81). CONCLUSIONS: Thrombolysis after MRI seems safe and effective in
      UTOS. This observation may encourage those who plan prospective placebo
      controlled trials of thrombolytics in this subgroup of stroke patients.

PMID- 21895878
TI  - The involvement of nitric oxide synthase neurons in enteric neuropathies.
AB  - Nitric oxide (NO), produced by the neural nitric oxide synthase enzyme (nNOS) is
      a transmitter of inhibitory neurons supplying the muscle of the gastrointestinal
      tract. Transmission from these neurons is necessary for sphincter relaxation that
      allows the passage of gut contents, and also for relaxation of muscle during
      propulsive activity in the colon. There are deficiencies of transmission from NOS
      neurons to the lower esophageal sphincter in esophageal achalasia, to the pyloric
      sphincter in hypertrophic pyloric stenosis and to the internal anal sphincter in
      colonic achalasia. Deficits in NOS neurons are observed in two disorders in which
      colonic propulsion fails, Hirschsprung's disease and Chagas' disease. In
      addition, damage to NOS neurons occurs when there is stress to cells, in
      diabetes, resulting in gastroparesis, and following ischemia and reperfusion. A
      number of factors may contribute to the propensity of NOS neurons to be involved
      in enteric neuropathies. One of these is the failure of the neurons to maintain
      Ca(2+) homeostasis. In neurons in general, stress can increase cytoplasmic
      Ca(2+), causing a Ca(2+) toxicity. NOS neurons face the additional problem that
      NOS is activated by Ca(2+). This is hypothesized to produce an excess of NO,
      whose free radical properties can cause cell damage, which is exacerbated by
      peroxynitrite formed when NO reacts with oxygen free radicals.

PMID- 21895877
TI  - Persistent epithelial barrier alterations in a rat model of postinfectious gut
      dysfunction.
AB  - BACKGROUND: Mucosal mast cells (MMCs), epithelial barrier function (EBF) and the
      enteric nervous system (ENS) are interactive factors in the pathophysiology of
      functional gastrointestinal disorders. We characterized postinfectious EBF
      alterations in the Trichinella spiralis infection model of MMC-dependent
      intestinal dysfunction in rats. METHODS: Sprague-Dawley rats were infected with
      T. spiralis. 30 +/- 2 days postinfection, jejunal EBF (electrophysiological
      parameters, fluorescein isothiocyanate-dextran fluxes and responses to
      secretagogues and MMC degranulators) was evaluated (Ussing chamber). In some
      experiments, participation of secretomotor neurons was examined by tetrodotoxin
      (TTX) pretreatment. Jejunal histology and MMC count and activity were also
      assessed. KEY RESULTS: 30 +/- 2 days postinfection, when only a low grade
      inflammation was observed, increased MMC number and activity were associated with
      altered EBF. EBF alterations were characterized by increased mucosal permeability
      and ion secretion. In T. spiralis-infected animals, secretory responses to
      serotonin (5-HT) and immunoglobulin E (IgE)-dependent activation of MMCs were
      reduced. In contrast, responses to substance P (SP) and capsaicin were similar in
      infected and noninfected animals. Neuronal blockade with TTX altered secretory
      responses to SP and capsaicin only in infected rats. CONCLUSIONS & INFERENCES:
      Trichinella spiralis infection in rats, at late stages, results in persistent
      postinfectious intestinal barrier dysfunctions and mucosal mastocytosis, with
      other signs suggestive of a low grade inflammation. The altered permeability and
      the TTX-independent hyporesponsiveness to 5-HT and IgE indicate epithelial
      alterations. Changes in responses to SP and capsaicin after neuronal blockade
      suggest an ENS remodeling during this phase. Similar long-lasting neuro
      epithelial alterations might contribute to the pathophysiology of functional and
      postinfectious gastrointestinal disorders.

PMID- 21895880
TI  - Apathy in acute stroke patients.
AB  - BACKGROUND AND PURPOSE: Apathy is a frequent disturbance in stroke patients. The
      aim of this case-control study was to elucidate whether apathy: (i) was secondary
      to stroke or related to hospitalization, (ii) was related to thalamic and
      striatocapsular stroke lesions, (iii) was independent from cognitive impairment
      and depression in the acute phase of stroke, (iv) was associated with clinical
      and demographical variables and (v) was associated with a worse functional
      outcome at discharge. METHODS: We assessed a sample of 94 consecutive patients
      with an acute (<=4 days) stroke (22 intracerebral haemorrhages, 72 cerebral
      infarcts), and a control group of 50 patients with acute coronary syndrome, with
      the 10-item Apathy Evaluation Scale-Clinical. We related apathy with cognition
      (MMSE), depression (Montgomery Asberg Depression Rating Scale) and with outcome
      (modified Rankin Scale). RESULTS: Apathy was present in 36 (38.3%) acute stroke
      patients but was also frequent in patients with acute coronary syndrome (24%).
      Stroke patients were more inaccurate in understanding their problems than
      patients with acute coronary syndrome (P=0.005). Logistic regression identified
      cerebral haemorrhage (OR=3.5), low educational level (OR=4.7) and a trend of
      right hemispherical lesion (OR=3.0) as independent predictors for apathy
      (R(2)=32.3%). Cognitive impairment and depression were not associated to apathy.
      Apathy was associated with a worse outcome (P=0.03). CONCLUSION: Apathy was
      frequent in acute stroke patients, and it was predicted by acute intracerebral
      haemorrhage and right hemispherical acute stroke lesion.

PMID- 21895882
TI  - The role of intima-media-thickness, ankle-brachial-index and inflammatory
      biochemical parameters for stroke risk prediction: a systematic review.
AB  - BACKGROUND: Despite important advances in therapeutic approaches in stroke, the
      options of acute treatment are still limited. Primary prevention represents
      another potentially highly efficient strategy. For effective prevention the early
      detection of subjects at risk is of utmost importance. Coinciding with a change
      in current understanding of atherosclerosis as an inflammatory, cross-organ
      disease, new parameters to assess the individual risk are emerging. METHODS:
      Systematic review of the potential of selected parameters for prediction of
      cerebrovascular events beyond detection of traditional risk factors that might
      expand the repertoire of primary prevention programs in stroke. RESULTS: An
      absolute carotid intima-media thickness difference of 0.1 mm increases the future
      risk of stroke by 13-18%. An ankle-brachial index <0.9 was associated with a
      relative risk of 2.33 (95% CI 2.02-2.68) for stroke. In patients with acute
      stroke and ABI values < 0.9 the risk for a new vascular event is significantly
      increased (HR 2.1; 95% CI 1.6-2.8). Measurements of several molecular biomarkers
      may be used to predict future vascular events independently of traditional risk
      factors. CONCLUSIONS: Based on the data presented, there is clear evidence that
      measurement of the ankle-brachial index identifies subjects of increased stroke
      risk in primary and secondary care settings as well as of stroke recurrence in
      acute stroke.

PMID- 21895881
TI  - Clinical and molecular genetic factors affecting postoperative seizure control of
      183 Chinese adult patients with low-grade gliomas.
AB  - BACKGROUND AND PURPOSE: Seizures are a common symptom of patients with primary
      brain tumors, particularly low-grade gliomas (LGGs). Poor seizure control after
      surgery has a great adverse impact on quality of life in these patients. The
      present study aimed to identify clinical and molecular genetic factors that
      influence postoperative seizure control. METHODS: A series of 183 LGGs were
      analyzed by denaturing high-performance liquid chromatography (DHPLC) for 1p and
      19q status and by immunohistochemical staining for expression of several
      molecular markers (P53, Ki-67, MMP-9 and MGMT), with particular emphasis on
      correlations with postoperative seizure control. Univariate and multivariate
      logistic regression analyses were used for statistic analysis. RESULTS: Of the
      183 patients, 134 (73.2%) patients presented with seizures. Most of
      oligodendrogliomas and oligoastrocytomas had LOH 1p and LOH 19q, which were
      rarely seen in combination in astrocytomas (P<0.001). Oligodendroglial tumors
      were more likely to locate in frontal lobe (P=0.011) and present calcification on
      MRI (P=0.024). Temporal location (P=0.014), and high expression of mutated P53
      (P=0.011) were associated with astrocytomas. Patients achieved much better
      seizure control after gross-total resection (P<0.001) than after subtotal
      resection. Patients without LOH 19q were more likely to have poor seizure control
      (P=0.004) than those with this alteration. Ki-67 was an independent molecular
      marker predicting poor seizure control (P=0.016) if over expressed. CONCLUSIONS:
      Gross total resection of the tumor, LOH 19q and low Ki-67 expression were
      associated with favorable seizure control after surgery for the patients with
      LGGs. The possible involvement of other factors should be investigated further.

PMID- 21895883
TI  - Off-label intravenous thrombolysis in acute stroke.
AB  - BACKGROUND AND PURPOSE: Therapy for stroke with intravenous tissue plasminogen
      activator (IV-tPA) is hampered by tight licensing restrictions; some of them have
      been discussed in recent literature. We assessed the safety and effectiveness of
      off-label IV-tPA in the clinical settings. METHODS: Retrospective analysis of all
      the patients treated with IV-tPA at our Stroke Unit. Patients were divided into
      two groups by licence criteria [on-label group (OnLG), off-label group (OffLG)].
      Primary outcome measures were symptomatic intracranial haemorrhages (sICH), major
      systemic haemorrhages, modified Rankin scale (mRS) and mortality rate at 3months.
      RESULTS: Five hundred and five patients were registered, 269 (53.2%) were
      assigned to OnLG and 236 (46.9%) to OffLG. Inclusion criteria for the OffLG were
      aged >80 years (129 patients), time from onset of symptoms to treatment over 3h
      (111), prior oral anticoagulant treatment with International Normalised
      Ratio<=1.7 (41), combination of previous stroke and diabetes mellitus (14),
      surgery or severe trauma within 3months of stroke (13), National Institutes of
      Health Stroke Scale score over 25 (11), intracranial tumours (5), systemic
      diseases with risk of bleeding (7) and seizure at the onset of stroke (2). No
      significant differences were identified between both groups regarding the
      proportion of sICH (OnLG 2.2% vs. OffLG 1.6%, P=0.78) or the 3-month mortality
      rate (11.1% vs. 19%: odds ratio (OR), 1.49; 95% CI, 0.86-2.55; P=0.14).
      Multivariate analysis showed no significant differences in functional
      independence at 3months between both groups (mRS <3 64.3% vs. 50.4%: OR mRS >2
      1.7; 95% CI, 0.96-2.5; P=0.07). CONCLUSION: Intravenous thrombolysis may be safe
      and efficacious beyond its current label restrictions.

PMID- 21895885
TI  - Continuous monitoring versus HOLTER ECG for detection of atrial fibrillation in
      patients with stroke.
AB  - BACKGROUND AND PURPOSE: Detection of atrial fibrillation is of vital importance
      because oral anticoagulation decreases the risk of a stroke by 64%. Current
      standards for stroke unit treatment require continuous electrocardiogram (ECG)
      monitoring for at least 24 h. Additionally, a 24-h HOLTER ECG (HOLTER) should be
      performed in selected patients. It remains unclear whether continuous monitoring
      at the bedside is equivalent to HOLTER for the detection of atrial fibrillation.
      Furthermore, we investigate how many additional patients with paroxysmal atrial
      fibrillation can be identified as a result of a longer duration of continuous
      monitoring. METHODS: In this study, we prospectively compared the detection rates
      of HOLTER and 24-h monitoring at the Stroke Unit at the University of Heidelberg
      over a period of 9 months. Continuous monitoring was analyzed by trained nurses,
      HOLTER by cardiologists. RESULTS: We included 370 patients with ischemic stroke
      or transient ischemic attack (TIA) in our study. Of these, 192 patients underwent
      HOLTER. Previously unknown atrial fibrillation was detected in 44 patients, 13
      patients had no atrial fibrillation in baseline ECG, but atrial fibrillation was
      detected by continuous monitoring. In two patients, the HOLTER showed atrial
      fibrillation; both patients had also been detected by continuous monitoring.
      Median time to detection of the atrial fibrillation during continuous monitoring
      was 43 h after hospitalization. CONCLUSION: In this study, use of HOLTER does not
      give any additional benefit in comparison with continuous monitoring with
      intermittent analysis by trained staff alone. The median detection time of 43 h
      emphasizes the importance of longer continuous monitoring.

PMID- 21895889
TI  - Impaired vascular remodeling in the yolk sac of embryos deficient in ROCK-I and
      ROCK-II.
AB  - Rho-associated coiled-coil-forming protein serine/threonine kinase (ROCK)
      consisting of two isoforms, ROCK-I and ROCK-II, functions downstream of the small
      GTPase Rho for assembly of actomyosin bundles. To examine the role of ROCK
      isoforms in vivo, we previously generated and examined mice deficient in each of
      the two isoforms individually. Here, we further examined the in vivo role of ROCK
      isoforms by generating mice deficient in both isoforms. Cross-mating of ROCK-I(+/
      ) ROCK-II(+/-) double heterozygous mice showed that all of the ROCK-I(-/-) ROCK
      II(-/-) homozygous mice die in utero before 9.5 days post-coitum (dpc) and ROCK
      I(-/-) ROCK-II(+/-) homo-heterozygous or ROCK-I(+/-) ROCK-II(-/-) hetero
      homozygous mice die during a period from 9.5 to 12.5 dpc, whereas mice of other
      genotypes survive until 12.5 dpc with the expected Mendelian ratio. All of the
      ROCK-I(+/-) ROCK-II(-/-) or ROCK-I(-/-) ROCK-II(+/-) mice showed impaired body
      turning and defective vascular remodeling in the yolk sac. Impairment of vascular
      remodeling was also observed in wild-type embryos treated ex vivo with a ROCK
      inhibitor, Y-27632. These results suggest that ROCK isoforms function redundantly
      during embryogenesis and play a critical role in vascular development.

PMID- 21895887
TI  - Parathyroid hormone and its effects on dental tissues.
AB  - In the current era, various pharmacological agents exist for osteoporosis
      management, and synthetic parathyroid hormone (PTH) (Teriparatide, Forteo) is one
      of the treatment options. Depending on the timing of administration, PTH has a
      unique ability to cause both bone apposition and bone resorption. This review
      focuses on the effects of PTH on the bone, specifically the jaw bones mandible
      and maxilla. The article briefly describes the fundamental mechanism of PTH
      action at the molecular level, as well as in experimental animals and in humans.
      It differentiates intermittent administration of PTH, especially at doses
      tolerated by humans that increase bone strength and prevent bone fractures, from
      continuous use that may lead to bone loss. In particular, it shows how
      intermittent administration of PTH can play a significant role in periodontal
      repair and implant success via stimulation of bone mineral content especially in
      the pre-alveolar region.

PMID- 21895888
TI  - Sodium-driven motor of the polar flagellum in marine bacteria Vibrio.
AB  - The Na(+) -driven bacterial flagellar motor is a molecular machine powered by an
      electrochemical potential gradient of sodium ions across the cytoplasmic
      membrane. The marine bacterium Vibrio alginolyticus has a single polar flagellum
      that enables it to swim in liquid. The flagellar motor contains a basal body and
      a stator complexes, which are composed of several proteins. PomA, PomB, MotX, and
      MotY are thought to be essential components of the stator that are required to
      generate the torque of the rotation. Several mutations have been investigated to
      understand the characteristics and function of the ion channel in the stator and
      the mechanism of its assembly around the rotor to complete the motor. In this
      review, we summarize recent results of the Na(+) -driven motor in the polar
      flagellum of Vibrio.

PMID- 21895890
TI  - A mutation in a mitochondrial dehydrogenase/reductase gene causes an increased
      sensitivity to oxidative stress and mitochondrial defects in the nematode
      Caenorhabditis elegans.
AB  - rad-8 is an interesting mutant that shows increased sensitivities to UV radiation
      and reactive oxygen species in the nematode Caenorhabditis elegans. In this
      study, we have characterized rad-8 and have found that rad-8 showed several
      phenotypes of mitochondrial dysfunction such as a decreased activity of the
      respiratory chain, increased generation of superoxide anions, increased oxidative
      damage, increased apoptosis, and abnormal mitochondrial structure. Our genetic
      analysis has also indicated that rad-8 has a causative mutation in the F56H1.6
      gene, which encodes a mitochondrial dehydrogenase/reductase. The functional role
      of RAD-8 may be evolutionarily conserved because expression of the putative human
      homologue RTN4IP/NIMP in rad-8 rescued the increased sensitivity to oxygen in rad
      8. These results suggest that RAD-8 plays an important role in oxygen metabolism
      in mitochondria in higher eukaryotes.

PMID- 21895886
TI  - Deep sequencing of short RNAs reveals novel microRNAs in minor salivary glands of
      patients with Sjogren's syndrome.
AB  - OBJECTIVES: Sjogren's syndrome is a complex autoimmune disease of the salivary
      gland with an unknown etiology, so a thorough characterization of the
      transcriptome would facilitate our understanding of the disease. We use ultradeep
      sequencing of small RNAs from patients with Sjogren's syndrome and healthy
      volunteers, primarily to identify and discover novel miRNA sequences that may
      play a role in the disease. METHODS: Total RNA was isolated from minor salivary
      glands of healthy volunteers and patients with either high or low salivary flow
      and sequenced on the SOLiD platform. Prediction of mature miRNAs from the
      sequenced reads was carried out using miRanalyzer, and expression was validated
      using Taqman qPCR assays. RESULTS: We validated the presence of six previously
      unidentified miRNA sequences in patient samples and in several cell lines. One of
      the validated novel miRNAs shows promise as a biomarker for salivary function.
      CONCLUSION: Sequencing small RNAs in the salivary gland is largely unprecedented,
      but here, we show the feasibility of discovering novel miRNAs and disease
      biomarkers by sequencing the transcriptome.

PMID- 21895884
TI  - Effect of rasagiline as adjunct therapy to levodopa on severity of OFF in
      Parkinson's disease.
AB  - BACKGROUND: The LARGO study demonstrated that rasagiline 1 mg/day as adjunct to
      levodopa significantly reduces OFF time to the same magnitude as adjunct
      entacapone. This substudy of LARGO aimed to assess the effect of rasagiline and
      entacapone on the motor symptoms of PD during the practically defined OFF state.
      METHODS: LARGO was a randomized, double-blind, multicenter trial that assessed
      the efficacy and safety of rasagiline (1 mg/day), entacapone (200 mg with each
      levodopa dose), and placebo in 687 levodopa-treated PD patients with motor
      fluctuations. A substudy of LARGO measured UPDRS motor scores in the practically
      defined OFF state in 32 rasagiline, 36 entacapone, and 37 placebo patients.
      RESULTS: Treatment with rasagiline produced a significant improvement over
      placebo of 5.64 units in UPDRS motor OFF score (P = 0.013 vs. placebo). By
      contrast, the effect of adjunct entacapone was not significant (P = 0.14 vs.
      placebo). Whereas rasagiline also showed a trend in reducing the UPDRS-ADL OFF
      score (P = 0.058 vs. placebo), no such trend was noted for entacapone (P = 0.26
      vs. placebo). Retrospective analysis, using the Bonferroni correction, of UPDRS
      motor subdomains further revealed that rasagiline, but not entacapone,
      significantly improved bradykinesia (P < 0.001) and showed trends for
      improvements in facial expression, speech, and axial impairment during OFF time.
      CONCLUSIONS: This study provides the first objectively measured evidence that
      adjunct rasagiline 1 mg/day is effective in reducing the severity of motor
      symptoms in the OFF state. This suggests a continuous effect of rasagiline 1
      mg/day throughout the day and night and is consistent with its extended duration
      of therapeutic action.

PMID- 21895891
TI  - Roles of histone chaperone CIA/Asf1 in nascent DNA elongation during nucleosome
      replication.
AB  - The nucleosome, which is composed of DNA wrapped around a histone octamer, is a
      fundamental unit of chromatin and is duplicated during the eukaryotic DNA
      replication process. The evolutionarily conserved histone chaperone cell cycle
      gene 1 (CCG1) interacting factor A/anti-silencing function 1 (CIA/Asf1) is
      involved in histone transfer and nucleosome reassembly during DNA replication.
      CIA/Asf1 has been reported to split the histone (H3-H4)(2)  tetramer into histone
      H3-H4 dimer(s) in vitro, raising a possibility that, in DNA replication, CIA/Asf1
      is involved in nucleosome disassembly and the promotion of semi-conservative
      histone H3-H4 dimer deposition onto each daughter strand in vivo. Despite
      numerous studies on the functional roles of CIA/Asf1, its mechanistic role(s)
      remains elusive because of lack of biochemical analyses. The biochemical studies
      described here show that a V94R CIA/Asf1 mutant, which lacks histone (H3-H4)(2) 
      tetramer splitting activity, does not form efficiently a quaternary complex with
      histones H3-H4 and the minichromosome maintenance 2 (Mcm2) subunit of the Mcm2-7
      replicative DNA helicase. Interestingly, the mutant enhances nascent DNA strand
      synthesis in a cell-free chromosomal DNA replication system using Xenopus egg
      extracts. These results suggest that CIA/Asf1 in the CIA/Asf1-H3-H4-Mcm2 complex,
      which is considered to be an intermediate in histone transfer during DNA
      replication, negatively regulates the progression of the replication fork.

PMID- 21895893
TI  - Inclusive health.
AB  - We propose the concept of Inclusive Health to encapsulate the Health for All
      ethos; to build on the rights-based approach to health; to promote the idea of
      inclusion as a verb, where a more proactive approach to addressing distinctive
      and different barriers to inclusion is needed; and to recognise that new
      initiatives in human resources for health can offer exciting and innovative ways
      of healthcare delivery. While Inclusive Education has become a widely recognised
      and accepted concept, Health for All is still contested, and new thinking is
      required to develop its agenda in line with contemporary developments. Inclusive
      Health refers both to who gets health care and to who provides it; and its ethos
      resonates strongly with Jefferson's assertion that 'there is nothing more
      unequal, than the equal treatment of unequal people'. We situate the timeliness
      of the Inclusive Health concept with reference to recent developments in the
      recognition of the rights of people with disability, in the new guidelines for
      community-based rehabilitation and in the World Report on Disability. These
      developments offer a more inclusive approach to health and, more broadly, its
      inter-connected aspects of wellbeing. A concept which more proactively integrates
      United Nations conventions that recognise the importance of difference -
      disability, ethnicity, gender, children - could be of benefit for global
      healthcare policy and practice.

PMID- 21895894
TI  - Structure-function relationships of the antibacterial activity of phenolic acids
      and their metabolism by lactic acid bacteria.
AB  - AIMS: To determine structure-function relationships of antibacterial phenolic
      acids and their metabolites produced by lactic acid bacteria (LAB). METHODS AND
      RESULTS: Minimum inhibitory concentrations (MICs) of 6 hydroxybenzoic and 6
      hydroxycinnamic acids were determined with Lactobacillus plantarum, Lactobacillus
      hammesii, Escherichia coli and Bacillus subtilis as indicator strains. The
      antibacterial activity of phenolic acids increased at lower pH. A decreasing
      number of hydroxyl groups enhanced the activity of hydroxybenzoic acids, but had
      minor effects on hydroxycinnamic acids. Substitution of hydroxyl groups with
      methoxy groups increased the activity of hydroxybenzoic, but not of
      hydroxycinnamic, acid. Metabolism of chlorogenic, caffeic, p-coumaric, ferulic,
      protocatechuic or p-hydroxybenzoic acids by L. plantarum, L. hammesii,
      Lactobacillus fermentum and Lactobacillus reuteri was analysed by LC-DAD-MS.
      Furthermore, MICs of substrates and metabolites were compared. Decarboxylated
      and/or reduced metabolites of phenolic acids had a lower activity than the
      substrates. Strain-specific metabolism of phenolic acids generally corresponded
      to resistance. CONCLUSIONS: The influence of lipophilicity on the antibacterial
      activity of hydroxybenzoic acids is stronger than that of hydroxycinnamic acids.
      Metabolism of phenolic acids by LAB detoxifies phenolic acids. SIGNIFICANCE AND
      IMPACT OF THE STUDY: Results allow the targeted selection of plant extracts for
      food preservation, and selection of starter cultures for fermented products.

PMID- 21895895
TI  - Effect of applying an arsenic-resistant and plant growth-promoting rhizobacterium
      to enhance soil arsenic phytoremediation by Populus deltoides LH05-17.
AB  - AIMS: Bioremediation of highly arsenic (As)-contaminated soil is difficult
      because As is very toxic for plants and micro-organisms. The aim of this study
      was to investigate soil arsenic removal effects using poplar in combination with
      the inoculation of a plant growth-promoting rhizobacterium (PGPR). METHODS AND
      RESULTS: A rhizobacterium D14 was isolated and identified within Agrobacterium
      radiobacter. This strain was highly resistant to arsenic and produced indole
      acetic acid and siderophore. Greenhouse pot bioremediation experiments were
      performed for 5 months using poplar (Populus deltoides LH05-17) grown on As
      amended soils, inoculated with strain D14. The results showed that P. deltoides
      was an efficient arsenic accumulator; however, high As concentrations (150 and
      300 mg kg(-1)) inhibited its growth. With the bacterial inoculation, in the 300
      mg kg(-1) As-amended soils, 54% As in the soil was removed, which was higher than
      the uninoculated treatments (43%), and As concentrations in roots, stems and
      leaves were significantly increased by 229, 113 and 291%, respectively. In
      addition, the As translocation ratio [(stems + leaves)/roots = 0.8] was
      significantly higher than the uninoculated treatments (0.5). About 45% As was
      translocated from roots to the above-ground tissues. The plant height and dry
      weight of roots, stems and leaves were all enhanced; the contents of chlorophyll
      and soluble sugar, and the activities of superoxide dismutase and catalase were
      all increased; and the content of a toxic compound malondialdehyde was decreased.
      CONCLUSIONS: The results indicated that the inoculation of strain D14 could
      contribute to the increase in the As tolerance of P. deltoides, promotion of the
      growth, increase in the uptake efficiency and enhancement of As translocation.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The use of P. deltoides in combination with
      the inoculation of strain D14 provides a potential application for efficient soil
      arsenic bioremediation.

PMID- 21895892
TI  - Efficacy and safety of zinc supplementation for adults, children and pregnant
      women with HIV infection: systematic review.
AB  - OBJECTIVES: To determine the efficacy and safety of zinc supplementary in
      children, adults and pregnant women with HIV infection. METHODS: We conducted a
      comprehensive search in Medline, Embase, the Cochrane Library, CBM, VIP and CNKI.
      Only randomized controlled trials conducted subsequent to the introduction of
      zinc supplementation were included in this systematic review. Two reviewers
      assessed and extracted data for analysis. RESULTS: Six trials with a total of
      1009 participants were included. The findings in this review suggested a benefit
      of zinc supplementation in reducing opportunistic infection for both adults and
      children with HIV infection. In terms of increase in zinc level and CD4 counts,
      however, only adults with HIV infection benefited. For other outcomes, such as
      viral load, mortality, mother-to-child transmission of HIV and foetal outcomes,
      zinc supplementation conferred no benefit over placebo. No adverse event related
      to zinc supplementation was found in all the included trials. CONCLUSION: Based
      on the current evidence, zinc supplementation seems to be beneficial in adult
      patients with HIV infection in some aspects. More research is needed in children
      and pregnant women. The influence of zinc dose, duration and usage of
      antiretroviral medicine also requires further investigation.

PMID- 21895896
TI  - Use of microwells to investigate the effect of quorum sensing on growth and
      antigen production in Bacillus anthracis Sterne 34F2.
AB  - AIM: The aim of this study was to investigate the role of quorum sensing in
      Bacillus anthracis growth and toxin production. METHODS AND RESULTS: A microwell
      plate culture method was developed to simulate the normal UK-licensed anthrax
      vaccine production run. Once established, sterile supernatant additions from a
      previous B. anthracis culture were made, and reductions in lag phase and early
      stimulation of the anthrax toxin component protective antigen (PA) were monitored
      using ELISA. The addition of the quorum-sensing inhibitor, fur-1, prolonged the
      lag phase and impeded PA production. Spin filters of various sizes were used to
      identify the molecular weight fraction of the sterile supernatant responsible for
      the autoinducer effect. A weight fraction between 5 and 10 kDa was responsible
      for the autoinducer effect; however, further identification using mass
      spectroscopy proved inconclusive. CONCLUSIONS: Quorum sensing mediated by the
      autoinducer two molecule plays a significant role in both B. anthracis growth and
      toxin production. SIGNIFICANCE AND IMPACT OF THE STUDY: While genomic analysis
      has eluded to the importance of LuxS and quorum sensing in anthrax, this is the
      first analysis using a production strain of B. anthracis and a quorum-sensing
      inhibitor to monitor the effect on growth and toxin production. This gives
      insights into anthrax pathogenicity and vaccine manufacture.

PMID- 21895897
TI  - Using temperature and time criteria to control the effectiveness of continuous
      thermal sanitation of piggery effluent in terms of set microbial indicators.
AB  - AIM: To determine the minimal conditions (temperature-time), necessary to achieve
      set sanitation targets for selected microbial indicators during the continuous
      thermal treatment of pig slurry. METHODS AND RESULTS: The effectiveness of
      thermal treatment between 55 and 96 degrees C was studied using Escherichia coli,
      enterococci, sulfite-reducing Clostridia (SRC), mesophilic culturable bacteria
      (MCB), F+-specific and somatic phages. Identification of SRC and MCB was
      performed using 16S rRNA gene analysis. Ten minutes at 70 degrees C or 1 h at 60
      degrees C was sufficient to reduce the vegetative bacteria by 4-5 log(10), but it
      had little effect on somatic phages nor on spore formers, dominated by
      Clostridium sp. At 96 degrees C, somatic phages were still detected, but there
      was a reduction of 3.1 log(10) for SRC and of 1.4 log(10) for MCB. At 96 degrees
      C, Clostridium botulinum was identified among the thermotolerant MCB. CONCLUSION:
      Only those hygienic risks relating to mesophilic vegetative bacteria can be
      totally eliminated from pig slurry treated at 60 degrees C (60 min) or 70 degrees
      C (<10 min). SIGNIFICANCE AND IMPACT OF THE STUDY: Hygiene standards based on the
      removal of the indicators E. coli and enterococci can easily be met by treatment
      as low as 60 degrees C (enabling, a low-cost treatment using heat recovery).
      However, even at 96 degrees C, certain pathogens may persist.

PMID- 21895899
TI  - Evaluation of an in vitro cell assay to select attenuated bacterial mutants of
      Aeromonas hydrophila and Edwardsiella tarda to channel catfish.
AB  - AIMS: To evaluate the feasibility of using an in vitro cell assay to select
      attenuated bacterial mutants. METHODS AND RESULTS: Using catfish gill cells G1B,
      the feasibility of using an in vitro assay instead of in vivo virulence assay
      using live fish to select attenuated bacterial mutants was evaluated in this
      study. Pearson correlation analysis between in vitro virulence to G1B cells and
      in vivo virulence of Aeromonas hydrophila and Edwardsiella tarda revealed that
      there was a significant correlation between the two (r = -0.768, P value = 3.7 *
      10(-16)). CONCLUSIONS: The in vitro cell assay might be initially used to screen
      large quantities of bacteria to select attenuated mutants of catfish pathogens.
      SIGNIFICANCE AND IMPACT OF THE STUDY: The in vitro cell assay using catfish gill
      cells to identify attenuated mutants of catfish pathogens will reduce cost
      involved in the in vivo virulence assay that requires many fish and aquariums.

PMID- 21895898
TI  - Cloning of exoinulinase gene from Penicillium janthinellum strain B01 and its
      high-level expression in Pichia pastoris.
AB  - AIMS: The aim of this study is to improve exoinulinase production by expression
      of a cloned exoinulinase gene inuA1 (GenBank accession no. JF961344) from
      Penicillium janthinellum strain B01 in Pichia pastoris. METHODS AND RESULTS: A
      full-length cDNA of exoinulinase gene (inuA1) was cloned from P. janthinellum
      strain B01 using RACE PCR. An open reading frame (ORF) of 2115 bp is interrupted
      by a single intron of 67 bp. The fragment encodes a signal peptide with 20 amino
      acids and a mature protein with 684 amino acids. The inuA1 was subcloned to the
      pPICZalphaC expression vector and successfully over-expressed in Pichia pastoris
      X-33. The highest activity of exoinlinase reached 272.8 U ml(-1) in the
      fermentation liquid. It was c. 11-fold of that produced by wild-strain B01. A
      large amount of fructose was identified after the hydrolysis of inulin with the
      crude recombinant exoinulinase. The recombinant exoinulinase was purified and
      characterized. The molecular weight of the purified recombinant exoinulianse was
      100 kDa. The mass spectrometry result indicated that the purified protein was
      indeed recombinant exoinulinase. The optimal pH and temperature of the purified
      recombinant exoinulianse were 4.5 and 50 degrees C, respectively. CONCLUSIONS: An
      exoinulinase gene of P. janthinellum strain B01 was cloned, sequenced and over
      expressed successfully in P. pastoris. SIGNIFICANCE AND IMPACT OF THE STUDY: Only
      a few genes have been cloned from P. janthinellum because its molecular biology
      is poorly understood. In this study, we cloned and over-expressed inuA1 gene of
      P. janthinellum in P. pastoris. This recombinant exoinulinase can be used to
      hydrolyse inulin to produce fructose and facilitate the biofuel production from
      inulin resources.

PMID- 21895900
TI  - Mugged by reality.

PMID- 21895901
TI  - Media coverage of cervical cancer and the HPV vaccine: implications for
      geographic health inequities.
AB  - OBJECTIVE: To describe the content of newspaper articles about cervical cancer
      and the human papillomavirus (HPV) vaccine published in Appalachia and identify
      potential differences in coverage as compared to the content of newspaper
      articles published in non-Appalachia Ohio. BACKGROUND: Individuals rely on media
      as an important source of health information. Inadequate coverage of health
      issues may reinforce health inequities such as the elevated cervical cancer
      incidence and mortality rates in Appalachia Ohio. METHODS: A content analysis was
      conducted of all newspaper articles about cervical cancer and the HPV vaccine
      published in Appalachia and non-Appalachia Ohio during 2006. FINDINGS: A total of
      121 published newspaper articles (42 in Appalachia and 79 in non-Appalachia)
      about cervical cancer and the HPV vaccine were identified. Articles published in
      Appalachia Ohio were significantly less likely than articles published in non
      Appalachia Ohio to provide information about the threat of cervical cancer and
      the efficacy of the HPV vaccine. Specifically, few articles published in
      Appalachia included information about the ability of the vaccine to prevent
      cervical cancer, the cost of the vaccine and the availability of assistance
      programmes for the un- and underinsured. CONCLUSIONS: Newspaper articles printed
      in the Appalachia region lacked vital information that could help promote uptake
      of the HPV vaccine. Health educators and healthcare providers should be aware
      that women from underserved geographic regions like Appalachia may have greater
      information needs regarding their risk of cervical cancer and the potential
      benefits of the HPV vaccine as compared to the general patient population.

PMID- 21895902
TI  - The Cochrane Library review titles that are important to users of health care, a
      Cochrane Consumer Network project.
AB  - BACKGROUND: The Cochrane Consumer Network is an internet-based community of
      international users of health care contributing to the work of The Cochrane
      Collaboration, whose mission is to inform healthcare decision making through
      development of systematic reviews of best evidence on healthcare interventions.
      OBJECTIVE: To prioritize existing review titles listed on The Cochrane Library
      from a healthcare user perspective, with particular emphasis on patients, carers
      and health consumers. DESIGN: An online survey was developed and after piloting
      was made available internationally. The broad dissemination strategy targeted
      Consumer Network members and Cochrane Review Group editorial staff to identify
      champions who notified patient support groups and participated in snowballing.
      The first part of the survey defined criteria that could be applied to review
      titles and asked survey respondents to rank them. The second part asked
      respondents to select a health area and prioritize review titles that were of
      importance to them. Each health area corresponded to a Cochrane Review Group.
      RESULTS AND DISCUSSION: Sufficient responses were obtained from 522 valid
      responses to prioritize review topics in 19 health areas. A total of 321
      respondents completed the titles assessment. The types of prioritized
      interventions were determined by the health area. An important observation was
      the emphasis on lifestyle and non-medication therapies in many of the included
      health areas. The clearest exception to this broad observation was where acute
      care is required such as antibiotics for acute respiratory tract and HIV
      associated infections and for cardiac conditions. For some cancers, advanced
      cancer interventions were prioritized. The most important criteria were for the
      title to convey a clear meaning and the title conveyed that the review would have
      an impact on health and well-being. The least important criteria were that the
      topic was newsworthy or prioritized in the healthcare system. CONCLUSION: This
      project was able to identify priority Cochrane review topics for users of health
      care in 19 of the 50 areas of health care covered by The Cochrane Collaboration.
      Reviews addressing lifestyle and non-medical interventions were strongly
      represented in the prioritized review titles. These findings highlight the
      importance of developing readable, informative lay summaries to support evidence
      based decision making by healthcare users.

PMID- 21895904
TI  - Monitoring and improving renal outcomes after heart transplantation.

PMID- 21895903
TI  - Low bone mineral density and nutritional vitamin D deficiency in pediatric renal
      transplant recipients: Assessment of risk factors and response to oral vitamin D
      therapy.
AB  - VitD deficiency and bone disease are common after Tx. Prevalence and risk factors
      for low VitD and BMD and response to VitD therapy were investigated in pediatric
      renal Tx recipients. 25-hydroxy VitD levels of 71 Tx were compared to 54 healthy
      AA children. DXA of 44 Tx were compared to 47 AA controls. Of Tx, 59% were AA.
      Majority (59.1%) of Tx were VitD deficient (23.9%) or insufficient (35.2%).
      Prevalence of low VitD levels was double in AA (73.9%) vs. non-AA Tx (37.7%), (p
      = 0.003). Low VitD among Tx was associated with AA ethnicity (p < 0.01), winter
      (p < 0.05), older age (p < 0.05), males (p < 0.05) and time <6 months post Tx (p
      < 0.05). Tx with low VitD were treated with oral ergocalciferol or
      cholecalciferol (23 each); 13% treated with ergocalciferol vs. 82.6% treated with
      cholecalciferol achieved repletion (p < 0.0001). Of 36 Tx with whole body DXA,
      19.5% had BMD (z < -1) after height adjustment. AA Tx had 3.4-fold higher risk of
      low BMD vs. controls (p < 0.05). Low VitD and BMD are prevalent in children after
      renal Tx. Better repletion of VitD is achieved with cholecalciferol.

PMID- 21895906
TI  - Evaluating the clinical efficacy of a primary care-focused, nurse-led,
      consultation liaison model for perinatal mental health.
AB  - In Australia, perinatal mental illness is common, although poorly identified and
      treated. Improved perinatal mental health depends on service provision models
      that reflect a focus on promotion, prevention, and early intervention, while
      facilitating improved referral pathways between primary health and specialist
      mental health services. In 2008, a contemporary community-based model of mental
      health service provision was developed as an alternative to the pre-existing
      hospital-based service model. The model is delivered primarily by mental health
      nurses using a consultation liaison framework. It provides for specialist mental
      health assessment and brief intervention in collaboration with the general
      practitioner, who remains the primary health provider. It also aims to raise
      community awareness and build capacity for the management of perinatal disorders
      in the primary care sector. Evaluation of the clinical effectiveness of the
      model, and the improvement in access for primary health providers and women, was
      conducted at 2 years from its implementation. Clinical effectiveness was
      evaluated by using comparative data from the Edinburgh Depression Scale and
      Depression Anxiety and Stress Scale, and the results demonstrated clinical
      efficacy. Improved attendance rates indicated that women preferred this community
      based service model as an alternative to the pre-existing service model.

PMID- 21895905
TI  - The second mini-transplant for unstable mixed chimerism within the first 100 days
      after hematopoietic stem cell transplant in severe thalassemia.
AB  - Allogeneic HSCT is the only curative treatment for severe thalassemia disease. MC
      occurs in one-third of these patients within the first two months after HSCT;
      this is a major risk factor of graft rejection, especially when RHCs are more
      than 25%. There is still no consensus for the management of MC, especially in the
      early phase of HSCT. The DLI has also been described in the treatment of MC
      following HSCT for hemoglobinopathies, but its success is still not guaranteed.
      The second HSCT has been an approach used in an attempt to cure patients who
      reject their graft. Concern about toxicity of conditioning regimen, the second
      HSCT is usually delayed for at least a year after the first HSCT. We would like
      to demonstrate the successful use of the second mini-allogeneic HSCT in
      hemoglobin E/beta-thalassemia with evidence of unstable MC in the first 100 days
      after allogeneic HSCT to prevent further graft loss after allogeneic HSCT.

PMID- 21895907
TI  - Bacterial sulfur cycling shapes microbial communities in surface sediments of an
      ultramafic hydrothermal vent field.
AB  - The ultramafic-hosted Logatchev hydrothermal field (LHF) is characterized by vent
      fluids, which are enriched in dissolved hydrogen and methane compared with fluids
      from basalt-hosted systems. Thick sediment layers in LHF are partly covered by
      characteristic white mats. In this study, these sediments were investigated in
      order to determine biogeochemical processes and key organisms relevant for
      primary production. Temperature profiling at two mat-covered sites showed a
      conductive heating of the sediments. Elemental sulfur was detected in the
      overlying mat and metal-sulfides in the upper sediment layer. Microprofiles
      revealed an intensive hydrogen sulfide flux from deeper sediment layers.
      Fluorescence in situ hybridization showed that filamentous and vibrioid,
      Arcobacter-related Epsilonproteobacteria dominated the overlying mats. This is in
      contrast to sulfidic sediments in basalt-hosted fields where mats of similar
      appearance are composed of large sulfur-oxidizing Gammaproteobacteria.
      Epsilonproteobacteria (7-21%) and Deltaproteobacteria (20-21%) were highly
      abundant in the surface sediment layer. The physiology of the closest cultivated
      relatives, revealed by comparative 16S rRNA sequence analysis, was characterized
      by the capability to metabolize sulfur components. High sulfate reduction rates
      as well as sulfide depleted in (34)S further confirmed the importance of the
      biogeochemical sulfur cycle. In contrast, methane was found to be of minor
      relevance for microbial life in mat-covered surface sediments. Our data indicate
      that in conductively heated surface sediments microbial sulfur cycling is the
      driving force for bacterial biomass production although ultramafic-hosted systems
      are characterized by fluids with high levels of dissolved methane and hydrogen.

PMID- 21895908
TI  - Microbial diversity and stratification of South Pacific abyssal marine sediments.
AB  - Abyssal marine sediments cover a large proportion of the ocean floor, but
      linkages between their microbial community structure and redox stratification
      have remained poorly constrained. This study compares the downcore gradients in
      microbial community composition to porewater oxygen and nitrate concentration
      profiles in an abyssal marine sediment column in the South Pacific Ocean.
      Archaeal 16S rRNA clone libraries showed a stratified archaeal community that
      changed from Marine Group I Archaea in the aerobic and nitrate-reducing upper
      sediment column towards deeply branching, uncultured crenarchaeotal and
      euryarchaeotal lineages in nitrate-depleted, anaerobic sediment horizons.
      Bacterial 16S rRNA clone libraries revealed a similar shift on the phylum and
      subphylum level within the bacteria, from a complex community of Alpha-, Gamma-
      and Deltaproteobacteria, Actinobacteria and Gemmatimonadetes in oxic surface
      sediments towards uncultured Chloroflexi and Planctomycetes in the anaerobic
      sediment column. The distinct stratification of largely uncultured bacterial and
      archaeal groups within the oxic and nitrate-reducing marine sediment column
      provides initial constraints for their microbial habitat preferences.

PMID- 21895909
TI  - Water column dynamics of Vibrio in relation to phytoplankton community
      composition and environmental conditions in a tropical coastal area.
AB  - Vibrio abundance generally displays seasonal patterns. In temperate coastal
      areas, temperature and salinity influence Vibrio growth, whereas in tropical
      areas this pattern is not obvious. The present study assessed the dynamics of
      Vibrio in the Arabian Sea, 1-2 km off Mangalore on the south-west coast of India,
      during temporally separated periods. The two sampling periods were signified by
      oligotrophic conditions, and stable temperatures and salinity. Vibrio abundance
      was estimated by culture-independent techniques in relation to phytoplankton
      community composition and environmental variables. The results showed that the
      Vibrio density during December 2007 was 10- to 100-fold higher compared with the
      February-March 2008 period. High Vibrio abundance in December coincided with a
      diatom-dominated phytoplankton assemblage. A partial least squares (PLS)
      regression model indicated that diatom biomass was the primary predictor
      variable. Low nutrient levels suggested high water column turnover rate, which
      bacteria compensated for by using organic molecules leaking from phytoplankton.
      The abundance of potential Vibrio predators was low during both sampling periods;
      therefore it is suggested that resource supply from primary producers is more
      important than top-down control by predators.

PMID- 21895910
TI  - The effect of inorganic particle concentration on bacteria-virus-nanoflagellate
      dynamics.
AB  - The effect of inorganic particle concentrations on bacteria-virus-nanoflagellate
      dynamics in an oligotrophic coastal system was investigated using a model
      aluminosilicate, kaolinite, with a modal size of 2.1 um. Virus-only, bacteria
      only and bacteria-virus-nanoflagellate incubations were carried out at increasing
      kaolinite concentrations to elucidate the microbial response. The sorption of
      bacteria and viruses to kaolinite particles was negligible over a concentration
      range of 1-50 mg l(-1). In contrast, the abundance of heterotrophic
      nanoflagellates was negatively correlated with kaolinite concentrations following
      both 48 and 96 h incubations. Calculated nanoflagellate bacterial ingestion rates
      were reduced by 5-35% depending on kaolinite particle concentration. In the
      bacteria-virus-nanoflagellate incubations viral production increased by 56 *
      10(3) to 104 * 10(3) VLPs ml(-1) h(-1) as a function of kaolinite particle
      concentration. Our results demonstrate for the first time that the interaction of
      microbial populations with inorganic particles can shift the balance between
      protist and virally mediated mortality of marine heterotrophic prokaryotes.

PMID- 21895911
TI  - Development of bioreporter assays for the detection of bioavailability of long
      chain alkanes based on the marine bacterium Alcanivorax borkumensis strain SK2.
AB  - Long-chain alkanes are a major component of crude oil and therefore potentially
      good indicators of hydrocarbon spills. Here we present a set of new bacterial
      bioreporters and assays that allow to detect long-chain alkanes. These reporters
      are based on the regulatory protein AlkS and the alkB1 promoter from Alcanivorax
      borkumensis SK2, a widespread alkane degrader in marine habitats. Escherichia
      coli cells with the reporter construct reacted strongly to octane in short-term
      (6 h) aqueous suspension assays but very slightly only to tetradecane, in line
      with what is expected from its low water solubility. In contrast, long-term
      assays (up to 5 days) with A. borkumensis bioreporters showed strong induction
      with tetradecane and crude oil. Gel-immobilized A. borkumensis reporter cells
      were used to demonstrate tetradecane and crude oil bioavailability at a distance
      from a source. Alcanivorax borkumensis bioreporters induced fivefold more rapid
      and more strongly when allowed physical contact with the oil phase in standing
      flask assays, suggesting a major contribution of adhered cells to the overall
      reporter signal. Using the flask assays we further demonstrated the effect of
      oleophilic nutrients and biosurfactants on oil availability and degradation by A.
      borkumensis. The fluorescence signal from flask assays could easily be captured
      with a normal digital camera, making such tests feasible to be carried out on,
      e.g. marine oil responder vessels in case of oil accidents.

PMID- 21895912
TI  - Genomic content of uncultured Bacteroidetes from contrasting oceanic provinces in
      the North Atlantic Ocean.
AB  - Bacteroidetes are widespread in marine systems where they play a crucial role in
      organic matter degradation. Whole genome analysis of several strains has revealed
      a broad glycolytic and proteolytic potential. In this study, we used a targeted
      metagenomic approach to investigate the degradation capabilities of distinct
      Bacteroidetes clades from two contrasting regions of the North Atlantic Ocean,
      the Polar Biome (BPLR) and the North Atlantic Subtropical (NAST). We present here
      the analysis of 76 Bacteroidetes fosmids, of which 28 encode the 16S rRNA gene as
      phylogenetic marker, and their comparison to complete Bacteroidetes genomes.
      Almost all of the 16S rRNA harbouring fosmids belonged to clades that we
      previously identified in BPLR and NAST. The majority of sequenced fosmids could
      be assigned to Bacteroidetes affiliated with the class Flavobacteria. We also
      present novel genomic information on the classes Cytophagia and Sphingobacteria,
      suggesting a capability of the latter for attachment to algal surfaces. In our
      fosmid set we identified a larger potential for polysaccharide degradation and
      cell surface attachment in the phytoplankton-rich BPLR. Particularly, two
      flavobacterial fosmids, one affiliated with the genus Polaribacter, showed a
      whole armoury of enzymes that likely function in degradation of sulfated
      polysaccharides known to be major constituents of phytoplankton cell walls. Genes
      involved in protein and peptidoglycan degradation, although present in both
      fosmid sets, seemed to have a slight preponderance in NAST. This study provides
      support for the hypothesis of a distinct specialization among marine
      Bacteroidetes for the degradation of certain types of polymers.

PMID- 21895913
TI  - Single cysteine substitution in Bacillus thuringiensis Cry7Ba1 improves the
      crystal solubility and produces toxicity to Plutella xylostella larvae.
AB  - Many Bacillus thuringiensis isolates have no demonstrated toxicity against
      insects. In this study, a novel holotype crystal protein gene cry7Ba1 was
      isolated from a 'non-insecticidal'B. thuringiensis strain YBT-978. The Cry7Ba1
      protein showed high toxicity against Plutella xylostella larvae after the
      crystals were dissolved at pH 12.5, suggesting that the 'non-insecticidal'
      properties of this protein were due to insolubility in the normal insect midgut
      pH environment. After the C-terminal half of Cry7Ba1 was replaced by that of
      Cry1Ac or Cry1C proteins, the recombinant protein inclusions could be dissolved
      at pH 9.5, and exhibited high toxicity against P. xylostella larvae. This result
      proved the insolubility of Cry7Ba1 crystal was determined by the structure of its
      C-terminal half. Further, six mutations were constructed by substituting cysteine
      residues with serine. Solubility studies showed that the crystals from mutants
      C697S, C834S and C854S could be dissolved at lower pH (10.5, 9.5 and 11.5
      respectively). Bioassays showed that crystals from mutant C834S were toxic to P.
      xylostella larvae. Our discoveries suggest that a single cysteine residue located
      in the C-terminal half of the protein determines the solubility and toxicity of
      some nontoxic crystal proteins. This study provides a strategy to isolate novel
      insecticidal crystal protein genes from 'non-insecticidal'B. thuringiensis
      strains.

PMID- 21895914
TI  - Detecting unknown sequences with DNA microarrays: explorative probe design
      strategies.
AB  - Designing environmental DNA microarrays that can be used to survey the extreme
      diversity of microorganisms existing in nature, represents a stimulating
      challenge in the field of molecular ecology. Indeed, recent efforts in
      metagenomics have produced a substantial amount of sequence information from
      various ecosystems, and will continue to accumulate large amounts of sequence
      data given the qualitative and quantitative improvements in the next-generation
      sequencing methods. It is now possible to take advantage of these data to develop
      comprehensive microarrays by using explorative probe design strategies. Such
      strategies anticipate genetic variations and thus are able to detect known and
      unknown sequences in environmental samples. In this review, we provide a detailed
      overview of the probe design strategies currently available to construct both
      phylogenetic and functional DNA microarrays, with emphasis on those permitting
      the selection of such explorative probes. Furthermore, exploration of complex
      environments requires particular attention on probe sensitivity and specificity
      criteria. Finally, these innovative probe design approaches require exploiting
      newly available high-density microarray formats.

PMID- 21895915
TI  - Rhodoferax-related pufM gene cluster dominates the aerobic anoxygenic
      phototrophic communities in German freshwater lakes.
AB  - The presence of aerobic anoxygenic phototrophs (AAPs) has been repeatedly
      reported from various marine environments, but their distribution in freshwater
      lakes was neglected until recently. We investigated the phylogenetic composition
      of AAP communities in 10 lakes in Northeastern Germany with different trophic
      status including oligotrophic Lake Stechlin and humic matter rich Lake Grosse
      Fuchskuhle. The AAP community was composed by members of Alpha- and
      Betaproteobacteria, but their contribution varied largely among the studied
      lakes. Our results show that AAP community composition in the studied lakes was
      affected mostly by pH and humic matter content. While alkaline lakes were mostly
      composed of Betaproteobacteria, the acidic and humic matter rich south-west (SW)
      basin of Lake Grosse Fuchskule was dominated (87%) by Alphaproteobacteria. The
      most frequent group within Betaproteobacteria was a cluster of pufM genes which
      was phylogenetically related to Rhodoferax representing 38.5% of all retrieved
      sequences. Alphaproteobacteria-related sequences had a broader phylogenetic
      diversity including six different taxa dominated by Sphingomonas- and Rhodobacter
      like bacteria in lakes with alkaline to neutral pH. In the acidic and humic
      matter-rich SW basin of Lake Grosse Fuchskuhle, however, Methylobacterium-related
      sequences dominated the AAP community. We suggest that the variable AAP community
      structure might reflect the potential of these bacteria to cope with the
      contrasting conditions in freshwater environments.

PMID- 21895918
TI  - High-resolution 2D and 3D cryo-TEM reveals structural adaptations of two stalk
      forming bacteria to an Fe-oxidizing lifestyle.
AB  - Aerobic neutrophilic Fe-oxidizing bacteria (FeOB) thrive where oxic and iron-rich
      anoxic waters meet. Here, iron microbial mats are commonly developed by stalk
      forming Fe-oxidizers adapted to these iron-rich gradient environments, somehow
      avoiding iron encrustation. Few details are known about FeOB physiology; thus,
      the bases of these adaptations, notably the mechanisms of interactions with iron,
      are poorly understood. We examined two stalked FeOB: the marine
      Zetaproteobacterium Mariprofundus ferrooxydans and a terrestrial
      Betaproteobacterium Gallionella-like organism. We used cryo-transmission electron
      microscopy and cryo-electron tomography to provide unprecedented ultrastructural
      data on intact cell-mineral systems. Both FeOB localize iron mineral formation at
      stalk extrusion sites, while avoiding surface and periplasmic mineralization. The
      M. ferrooxydans cell surface is densely covered in fibrils while the terrestrial
      FeOB surface is smooth, suggesting a difference in surface chemistry. Only the
      terrestrial FeOB exhibited a putative chemotaxis apparatus, which may be due to
      differences in chemotaxis mechanisms. Both FeOB have a single flagellum, which
      alone is insufficient to account for cell motion during iron oxidation,
      suggesting that stalk extrusion is a mechanism for motility. Our results
      delineate the physical framework of iron transformations and characterize
      possible structural adaptations to the iron-oxidizing lifestyle. This study shows
      ultrastructural similarities and differences between two distinct FeOB, setting
      the stage for further (e.g. genomic) comparisons that will help us understand
      functional differences and evolutionary history.

PMID- 21895917
TI  - Overlapping and unique contributions of two conserved polysaccharide loci in
      governing distinct survival phenotypes in Vibrio vulnificus.
AB  - As an aetiological agent of bacterial sepsis and wound infections, Vibrio
      vulnificus is unique among the Vibrionacea. Its continued environmental
      persistence and transmission are bolstered by its ability to colonize shellfish
      and form biofilms on various marine biotic surfaces. We previously identified a
      polysaccharide locus, brp, which contributes to the survival phenotypes of
      biofilm formation, rugose colony formation and stress resistance. Here, we
      describe a second polysaccharide locus, rbd (regulation of biofilm development),
      which also enhanced biofilm formation when expressed. Despite this functional
      overlap, the development of stress resistance and rugosity could be uniquely
      attributed to brp expression, whereas rbd expression augmented aggregate
      formation. Simultaneous expression of both loci led to the formation of a
      dramatic pellicle and maximum biofilm formation. Unlike the brp locus,
      transcription of the rbd locus was regulated not by c-di-GMP, but by a response
      regulator (RbdG) that was encoded within the locus. We propose that the ability
      to regulate the expression of polysaccharides with overlapping and unique
      characteristics in response to different environmental cues enables V. vulnificus
      to 'fine tune' its biofilm lifestyle to the prevailing environmental conditions
      and maximally benefit from the characteristics associated with each
      polysaccharide.

PMID- 21895919
TI  - Alcohol dehydrogenase expression as a biomarker of denitrification activity in
      activated sludge using methanol and glycerol as electron donors.
AB  - Carbon sources such as methanol and glycerol are used for enhancing
      denitrification at wastewater treatment plants, which are required to meet
      increasingly stringent effluent nitrogen limits. Consequently, dosing strategies
      for these compounds could benefit from the development and application of
      molecular activity biomarkers to infer and distinguish between methanol- or
      glycerol-based denitrification in activated sludge. In this study, the
      applicability of genes coding for methanol dehydrogenase (mdh2 and mxaF) and
      glycerol dehydrogenase (dhaD) as potential biomarkers of denitrification activity
      using these specific substrates was explored and confirmed using a two-pronged
      approach. First, during short-term spikes of activated sludge biomass with
      glycerol, the ability of dhaD mRNA concentrations to closely track nitrate
      depletion profiles was demonstrated. Second, a high-degree of correlation of the
      mRNA concentrations of mdh2, mxaF and dhaD with methanol- and glycerol-based
      denitrification kinetics during long-term bioreactor operation using these
      substrates was also shown. Based on these results, expression of mdh2, mxaF and
      dhaD genes are promising biomarkers of in situ denitrification activity on
      methanol and glycerol, respectively, in mixed-culture engineered wastewater
      treatment processes.

PMID- 21895916
TI  - Accurate analysis of prevalence of coccidiosis in individually identified wild
      cranes in inhabiting and migrating populations in Japan.
AB  - Eimeria gruis and E. reichenowi cause coccidiosis, a major parasitic disease of
      cranes. By non-invasive molecular approaches, we investigated the prevalence and
      genetic characterization of pathogens in two Japanese crane habitats; one is
      Hokkaido inhabited by the endangered red-crowned crane, and the other is Izumi in
      Kyushu where populations that consist mainly of vulnerable hooded and white-naped
      cranes migrate in winter. The non-invasively collected faecal samples from each
      wintering population were first subjected to host genomic DNA-targeted analyses
      to determine the sample origin and avoid sample redundancy. Extremely high
      prevalence was observed in the Izumi populations (> 90%) compared with the
      Hokkaido population (18-30%) by examining 470 specimens by microscopy and PCR
      based capillary electrophoresis (PCR-CE), using genetic markers in the second
      internal transcribed spacer (ITS2). Correspondence analysis of PCR-CE data
      revealed differences in community composition of coccidia between hooded and
      white-naped cranes. 18S rRNA and ITS2 sequences were determined from single
      oocysts excreted by red-crowned and hooded cranes. Phylogenetic analysis of 18S
      rRNA suggested that E. reichenowi was polyphyletic while E. gruis was
      monophyletic. Together with PCR-CE data, these results indicate different host
      specificity among the E. reichenowi type. Our data suggest that E. reichenowi
      comprises multiple species.

PMID- 21895921
TI  - The role of reprogramming in sacral nerve modulation for constipation.

PMID- 21895922
TI  - Impact of early reoperation after resection for colorectal cancer on long-term
      oncological outcomes.
AB  - AIM: Whether reoperation in the postoperative period adversely affects oncologic
      outcomes for colorectal cancer patients undergoing resection has not been well
      characterized. The aim of this study was to determine whether long-term
      oncological outcomes are affected for patients who undergo repeat surgery in the
      early postoperative period. METHOD: From a prospective colorectal cancer
      database, patients who underwent resection for colorectal cancer between 1982 and
      2008 and were reoperated within 30 days after surgery (group A) were matched for
      age (+/-5 years), gender, year of surgery (+/-2 years), American Society of
      Anesthesiology score, tumor site (colon or rectum), cancer stage and
      differentiation with patients who did not undergo reoperation (group B). The two
      groups were compared for overall survival (OS), disease-free survival (DFS) and
      local recurrence (LR). RESULTS: In total, 89 reoperated patients (45 rectal, 44
      colon cancer) were matched to an equal number of non-reoperated patients.
      Anterior resection (39.2%) and right hemicolectomy (19.1%) were predominant
      primary operations. Indications for reoperation were anastomotic leak/abscess
      (n=40, 45%), massive bleeding (n=15, 16.9%), bowel obstruction (n=11, 12.4%),
      wound complications (n=9, 10.1%) and other indications (n=14, 15.6%). Group A had
      significantly greater overall morbidity (100% vs 27%, P=0.001) and required more
      blood transfusions (20.2% vs 7.9%, P=0.045). Adjuvant therapy use, on the other
      hand, was more common in group B (23.6% vs 12.3%, P=0.1). The 5-year OS and DFS
      were lower in the reoperated group (OS 55.3% vs 66.4%, P=0.02; DFS 50.8% vs
      60.8%, P=0.06, respectively). Five-year LR was slightly lower in the reoperated
      group (2.9% vs 6.3%, P=0.34). CONCLUSIONS: Compared with non-reoperated patients
      matched for patient, tumour and operative characteristics, patients reoperated in
      the early postoperative period have worse long-term oncological outcomes.
      Adoption of strategies to reduce the risk of reoperation may be associated with
      the additional advantage of improved oncological outcomes in addition to the
      short-term advantages.

PMID- 21895923
TI  - Intra-operative oxygen delivery in infusion volume-optimized patients undergoing
      laparoscopic colorectal surgery within an enhanced recovery programme: the effect
      of different analgesic modalities.
AB  - AIM: Patients undergoing major open surgery who have an indexed oxygen delivery
      (DO(2) I) > 600 ml/min/m(2) have been shown to have a lower incidence of
      morbidity and mortality compared with those whose DO(2) I is below this level.
      Laparoscopy and Trendelenburg positioning cause a reduction in DO(2) I. We aimed
      to quantify the effect of the type of analgesia on DO(2) I and to correlate the
      DO(2) I achieved with the incidence of anastomotic leakage in patients undergoing
      laparoscopic surgery. METHOD: Following ethical approval, patients were
      randomized to receive spinal anaesthesia (Group S), epidural analgesia (Group E)
      or intravenous morphine (Group P) followed by postoperative patient-controlled
      analgesia (PCA). In addition to standard monitoring, oesophageal Doppler
      monitoring of the stroke volume allowed directed intravenous fluid therapy. The
      mean DO(2) I was compared with the anastomotic leakage rate. RESULTS: Seventy
      five patients were recruited (Group S, 27; Group E, 23; Group P, 25). The mean
      (range) DO(2) I for all patients was 490 (230-750) ml/min/m(2) . The analgesic
      modality had no effect on DO(2) I. Of the 18 patients with a DO(2) I of < 400
      ml/min/m(2) , four (22%) developed anastomotic leakage compared with one (%) of
      the 57 patients with a DO(2) I of > 400 ml/min/m(2) (P = 0.01). CONCLUSION: The
      analgesic modality used had no effect on the DO(2) I achieved. Anastomotic
      leakage was significantly higher in patients with a DO(2) I of < 400 ml/min/m(2)
      . A further study assessing the outcome after raising the DO(2) I with inotropes
      is required.

PMID- 21895924
TI  - The ileo neo-rectal anastomosis in patients with familial adenomatous polyposis:
      a prospective case series with long-term follow up.
AB  - AIM: In patients with familial adenomatous polyposis (FAP), removal of the
      colonic mucosa is essential to reduce the lifetime risk of developing cancer).
      For this purpose, ileo-pouch anal anastomosis (IPAA) has been the gold standard,
      but morbidity related to the dissection of the pelvis remains substantial. In an
      attempt to reduce the procedure-related complications of pelvic dissection,
      ileoneo-rectal anastomosis (INRA) has been developed. In this case series of FAP
      patients, the long-term functional results, morbidity and quality of life (QoL)
      of the INRA procedure were evaluated and compared with its early outcome. METHOD:
      Long-term follow up of a consecutive group of eight FAP patients with an INRA
      procedure (between 1998 and 2005) was undertaken. Data on functional results,
      complications, manometry and endoscopy were recorded prospectively. RESULTS:
      Eight patients with FAP underwent the INRA procedure. The median number of
      defaecations over 24 h was five. No pelvic sepsis or bladder dysfunction
      occurred. One patient, in whom concomitant Crohn's disease was diagnosed in
      retrospect, was converted to IPAA. In the INRA patients, no sexual dysfunction
      occurred. Endoscopic examination showed normal mucosa without any evidence of
      polyp formation. CONCLUSION: Restorative surgery by means of the INRA procedure
      yields good functional results in FAP patients, without any pelvic dissection
      related morbidity or regrowth of polyps in the neo-rectum.

PMID- 21895920
TI  - Efficacy and safety of mitiglinide versus nateglinide in newly diagnose patients
      with type 2 diabetes mellitus: a randomized double blind trial.
AB  - This study was performed to examine the efficacy and safety of mitiglinide in
      type 2 diabetes patients (T2DM). Enrolled patients had received treatment with
      diet and exercise in the previous 3 months with glycosylated haemoglobin (HbA1c)
      7-10%, and were randomized to receive mitiglinide (n = 111, 5-20 mg/meal) or
      nateglinide (n = 114,60-120 mg/meal) for 16 weeks. Primary and secondary efficacy
      endpoints were assessed by the changes in HbA1c, fasting blood glucose (FBG) and
      postprandial glucose (PBG) levels. The baseline HbA1c value was 8.2 and 8.3% in
      both groups. At the end of study, the reduction of HbA1c values from baseline by
      mitiglinide was slightly more than that by nateglinide (-1.11% vs. -0.76%), but
      not statically significant (p = 0.06). Final FBG and PBG were comparable for the
      two treatments. There were 2.8% subjects treated with nateglinide who had
      hypoglycaemic episodes, but none in the mitiglinide treatment group. The results
      indicate that mitiglinide and nateglinide had similar effects on FBG, PBG and
      HbA1c in T2DM patients after the 16-week treatments.

PMID- 21895925
TI  - Laparoscopic repair of primary perineal hernias: the approach of choice in the
      21st century.
AB  - Perineal hernias are rare and result from the herniation of a viscus through the
      pelvic floor. Symptomatic perineal hernias are repaired surgically, historically
      via an open perineal, abdominal or abdominoperineal approach. We describe
      laparoscopic repair of a primary perineal hernia with mesh using the
      transabdominal approach. We believe that for uncomplicated primary perineal
      hernias laparoscopic repair is technically feasible, and associated with rapid
      recovery and minimal complications.

PMID- 21895926
TI  - Biological implants in sphincter augmentation offer a good short-term outcome
      after a sphincter repair.
AB  - AIM: Long-term results of the overlapping sphincter repair (OSR) have been
      disappointing, attributed to poor tissue quality that deteriorates with time.
      Biological grafts enforce tissues. The aim was to compare functional outcome and
      quality of life at 1 year with and without Permacol reinforcement to evaluate
      short-term benefit. METHOD: From November 2007 to November 2008, women undergoing
      OSR using Permacol (group 1, n = 10) under institutional review board approval
      (safety trial) were age matched with patients from an institutional review board
      approved database (group 2, n = 10) who underwent the traditional OSR. Permacol
      mesh was placed under the two overlapped muscles. Group 2 underwent traditional
      repair. Preoperative and postoperative management of the groups was similar. The
      Fecal Incontinence Severity Index (FISI), the Cleveland Clinic Incontinence Score
      (CCFIS) and the Fecal Incontinence Quality of Life (FIQL) scale were used
      preoperatively and 1 year post-surgery. RESULTS: No significant differences in
      demographics, symptom duration, number of vaginal deliveries, comorbidities and
      symptom severity were noted. Group 2 underwent concomitant procedures. Group 1
      reported no complications. Group 2 reported urinary retention and dehiscence. A
      significant difference was found in preoperative and postoperative FIQL subscales
      of coping/behaviour between groups. However, comparing the pre and post scores,
      significant improvements on FISI (P = 0.02), the CCFIS (P = 0.005) and two
      subscales of FIQL (coping/behaviour, P = 0.02, and embarrassment, P = 0.01) were
      found in group 1. Patient satisfaction was higher in group 1. CONCLUSION:
      Biologic tissue enhancers (Permacol) do not add morbidity. Sphincter augmentation
      results in significant improvement in continence and quality of life scores
      compared with the preoperative scores in the short term over traditional repair.
      Long-term studies are needed to determine if this effect is sustained.

PMID- 21895928
TI  - Regenerative medicine in urology.
AB  - The term 'regenerative medicine' encompasses strategies for restoring or renewing
      tissue or organ function by: (i) in vivo tissue repair by in-growth of host cells
      into an acellular natural or synthetic biomaterial, (ii) implantation of tissue
      'engineered'in vitro by seeding cultured cells into a biomaterial scaffold, and
      (iii) therapeutic cloning and stem cell-based tissue regeneration. In this
      article, we review recent developments underpinning the emerging science of
      regenerative medicine and critically assess where successful implementation of
      novel regenerative medicine approaches into urology practice might genuinely
      transform the quality of life of affected individuals. We advocate the need for
      an evidence-based approach supported by strong science and clinical objectivity.

PMID- 21895929
TI  - Tumour in solitary kidney: laparoscopic partial nephrectomy vs laparoscopic
      cryoablation.
AB  - OBJECTIVES: We compare perioperative, functional and intermediate-term
      oncological outcomes of laparoscopic partial nephrectomy (LPN) vs laparoscopic
      cryoablation (LCA) for small renal tumour in patients with a solitary kidney. A
      treatment algorithm is also proposed. PATIENT AND METHODS: Over a 10-year period
      (02/1998-09/2008), 78 patients with a small tumour in a functionally solitary
      kidney underwent LPN (n = 48) or LCA (n = 30). Baseline, perioperative, and
      follow-up data were collected prospectively and analyzed retrospectively.
      RESULTS: Demographic data were similar between the LPN and LCA groups. Tumours
      were somewhat larger (3.2 vs 2.6 cm) in the LPN group. LPN was associated with
      greater blood loss (391 vs 162 mL; P = 0.003), and trended towards more post
      operative complications (22.9% vs 6.7%; P = 0.07). By 3 months post-operative,
      eGFR decreased by 14.5% and 7.3% after LPN and LCA, respectively (P = 0.02). Post
      operative temporary dialysis was required after 3 LPN (6.2% vs 0%, P = 0.16).
      Median follow-up time for LPN and LCA was 42.7 and 60.2 months, respectively.
      Local recurrence was detected in 4 (13.3%) LCA patients only (P = 0.02). Overall
      survival was comparable between LPN and LCA at 3 and 5 years, respectively (P =
      0.74). The LPN group had superior cancer-specific and recurrence-free survival at
      3 and 5 years compared to the LCA group (P < 0.05, for all comparisons).
      CONCLUSIONS: Given adequate technical expertise, both LPN and LCA are viable
      nephron-sparing options for patients with tumour in a solitary kidney. Although
      LCA is technically easier and has superior functional outcomes, oncologic
      outcomes are superior after LPN.

PMID- 21895927
TI  - Cavernous smooth muscle hyperplasia in a rat model of hyperlipidaemia-associated
      erectile dysfunction.
AB  - What's known on the subject? and what does the study add? Increased cavernous
      smooth muscle content has been repeatedly observed in rat models of
      hyperlipidaemia - associated erectile dysfunction. This study shows that the
      increased smooth muscle content is due to hyperplasia. OBJECTIVE: * To
      investigate the structural changes, including possible smooth muscle hyperplasia,
      in the penis of a hyperlipidaemia-associated erectile dysfunction (ED) animal
      model. MATERIALS AND METHODS: * Hyperlipidaemia was induced in rats through a
      high-fat diet. * Penile tissues of normal and hyperlipidaemic rats were stained
      with Alexa-488-conjugated phalloidin and/or with antibodies against rat
      endothelial cell antigen, neuronal nitric oxide synthase (nNOS), and collagen
      type IV (Col-IV) before image and statistical analyses were carried out. * The
      main outcome measures were the smooth muscle, endothelial, Col-IV and nNOS
      content of the corpus cavernosum. RESULTS: * Phalloidin intensely stained all
      smooth muscle in the penis, revealing the circular and longitudinal components of
      cavernous smooth muscle (CSM). * The CSM content was significantly higher in the
      hyperlipidaemic than in the normal rats (P < 0.05). * Cell numbers in both
      circular and longitudinal CSM were significantly higher in the hyperlipidaemic
      than in the normal rats (P < 0.05). * Cavernous endothelial content was
      significantly lower in hyperlipidaemic than in normal rats (P < 0.05). * nNOS
      positive nerves within the dorsal nerves, around the dorsal arteries, and in the
      corpora cavernosa were all significantly lower in the hyperlipidaemic than in the
      normal rats (P < 0.05). CONCLUSIONS: * Hyperlipidaemia is associated with reduced
      nNOS-positive nerves, reduced endothelium, and increased CSM in the penis. * The
      increased CSM is attributable to hyperplasia. * These structural changes may
      explain why hyperlipidaemic men are more likely to develop ED.

PMID- 21895930
TI  - Focal laser interstitial thermotherapy (LITT) at 980 nm for prostate cancer:
      treatment feasibility in Dunning R3327-AT2 rat prostate tumour.
AB  - OBJECTIVE: To examine the feasibility and reproducibility of laser interstitial
      thermotherapy (LITT) as a minimally invasive method for the treatment of prostate
      cancer. MATERIALS AND METHODS: Heterotopic tumours of prostatic adenocarcinoma
      (Dunning R3327-AT2) were induced in 10 male Copenhagen rats. After preoperative
      magnetic resonance imaging (MRI), a 10-mm cylindrical diffusing fibre developed
      by our research department was inserted under ultrasonographic guidance into the
      tumour. LITT was performed with a 980-nm diode laser (power 5 W) for 75 s
      (fluence rate of 1145 J/cm(2)). Non-enhanced T2-weighted and dynamic gadolinium
      enhanced T1-weighted MRI examinations were performed at baseline, 1 and 48 h
      after the procedure and correlated with histological findings. RESULTS: The
      necrosis lesions induced by LITT were visible on MRI. The mean (SD) ellipsoid
      necrosis volumes were 0.748 (0.075) mL at 1 h and 0.982 (0.052) mL at 48 h after
      the LITT procedure, and significantly different (P < 0.001). Histological
      analysis showed a strong correlation (r = 0.87) with the mean necrosis volume
      obtained by MRI at 48 h after LITT. CONCLUSIONS: In a prostatic adenocarcinoma
      model, 980-nm LITT induces reproducible necrosis volumes. Further
      characterization of the response to LITT in an animal model and in human tissues
      will be important in establishing the efficacy of the procedure for prostate
      cancer focal therapy.

PMID- 21895932
TI  - The effect of surgical intervention for stress urinary incontinence (UI) on post
      prostatectomy UI during sexual activity.
AB  - OBJECTIVE: To determine the impact of anti-incontinence surgical procedures
      (artificial urinary sphincter [AUS] or male sling) on bother due to urinary
      incontinence (UI) during sexual activity after radical prostatectomy (RP).
      PATIENTS AND METHODS: Between October 2000 and December 2007, 27 men in a large
      single-surgeon RP series underwent anti-incontinence surgery with an AUS or male
      sling. In all, 16 of these 27 men completed a questionnaire retrospectively
      capturing bother attributable to UI during arousal and orgasm and the impact of
      the AUS/male sling on UI and sexual quality of life (QoL). RESULTS: In all, 15
      men were evaluable. Of these, 11 were sexually active; four and seven men
      underwent AUS and sling placement, respectively. All 11 men had a marked
      improvement in stress UI symptoms, which was the primary indication for surgery.
      All men undergoing AUS had an improvement in their sexual QoL, and most (three of
      four men) indicated marked improvement. Slightly more than half of men undergoing
      the sling procedure reported marked improvement in sexual QoL. CONCLUSIONS: Our
      study shows a beneficial effect of anti-incontinence surgery on UI during sexual
      activity. Whether these surgical approaches would benefit men with significant
      bother due to UI limited to sexual activity warrants further investigation.

PMID- 21895933
TI  - Automatic evaluation of ultrasonography-estimated bladder weight and bladder wall
      thickness in community-dwelling men with presumably normal bladder function.
AB  - OBJECTIVE: To identify measurements of ultrasonography (US)-derived bladder wall
      thickness (BWT) and bladder weight in community-dwelling men with presumably
      normal bladder function. SUBJECTS AND METHODS: A total of 100 male volunteers
      underwent transabdominal US measurements of BWT and bladder weight, using the BVM
      9500 bladder scanner (Verathon Medical, Bothell, WA, USA), at a variety of
      bladder filling volumes. The data were explored for any correlation between
      measurements of BWT and US-estimated bladder weight (UEBW) with subject age,
      height, weight, body mass index (BMI), International Consultation on Incontinence
      Questionnaire-Male Lower Urinary Tract Symptoms (ICIQ M-LUTS) score,
      International Prostate Symptom Score (IPSS) and IPSS Quality of Life index (IPSS
      QoL). RESULTS: Several statistically significant but weak correlations were
      observed: BWT and weight (r = 0.216, P = 0.032); BWT and BMI (r = 0.246, P =
      0.014); UEBW and weight (r = 0.304, P = 0.002); and UEBW and BMI (r = 0.260, P =
      0.009). Bladder filling volume appeared to have a greater effect on BWT than on
      UEBW, although this could not be determined accurately. There was a substantial
      difference in measurements of BWT and UEBW in the assessment of inter- and intra
      observer reliability testing. CONCLUSION: Further studies are required to
      validate automated measurements of BWT and UEBW and to investigate such
      measurements in the symptomatic and asymptomatic male population.

PMID- 21895934
TI  - The impact of social networks and partnership status on treatment choice in men
      with localized prostate cancer.
AB  - OBJECTIVES: To determine whether martial status and social support impact
      treatment choice. The decision to pursue radical prostatectomy for prostate
      cancer is often influenced by factors outside the realm of tumour risk, such as a
      man's support system at home. PATIENTS AND METHODS: We performed a retrospective
      cohort study of 418 low-income men who were diagnosed with non-metastatic
      prostate cancer and underwent definitive treatment with either radical
      prostatectomy or radiotherapy. We performed univariate and multivariate mixed
      effects logistic regression analysis, with the dependent variable being treatment
      type. Confidence intervals (CIs) for the predicted probabilities and relative
      risks were derived using bias-corrected bootstrapping with 1000 repetitions.
      RESULTS: Men with two or more members in their support system were more likely to
      be older, Hispanic, have less than a high school education, earn more than US
      $1500 monthly, have high-risk disease and be in a significant relationship. In
      multivariate analysis, partnered men with fewer than two social support members
      (relative risk, RR, 1.23; 95% CI, 1.02-1.63) were more likely to undergo surgery,
      whereas men who were morbidly obese (RR, 0.46; 95% CI, 0.09-0.88), high school
      graduates (RR, 0.80; 95% CI, 0.64-0.99) or had high-risk disease (RR, 0.58; 95%
      CI, 0.44-0.85) were less likely to undergo surgery than their respective referent
      groups. Partnered men with two or more social support members were no more likely
      to undergo surgery than unpartnered men who lacked any social support.
      CONCLUSIONS: In the present study cohort, married men with fewer than two members
      in their social network were more likely to have undergone surgery. Although
      marital status is often used as a proxy for social support, we find that the
      quality of support and partner may impact treatment type more than the extent of
      the social matrix.

PMID- 21895935
TI  - Diagnosis of isolated high-grade prostatic intra-epithelial neoplasia: proposal
      of a nomogram for the prediction of cancer detection at saturation re-biopsy.
AB  - Study Type--Diagnostic (case series). Level of Evidence 4. What's known on the
      subject? And what does the study add? Multifocality, age, PSA values, and biopsy
      protocols regarding the predictive value of high grade PIN have been discussed
      extensively in the literature. Our study developed for the first time a
      predictive nomogram that could be helpful for patient counselling and to guide
      the urologist to perform rPBX after an initial diagnosis of isolated HGPIN.
      OBJECTIVE: * To evaluate factors that may predict prostate cancer (PCa) detection
      after the initial diagnosis of high-grade prostatic intra-epithelial neoplasia
      (HGPIN) on prostate biopsy (PBx) with six to 24 random cores. PATIENTS AND
      METHODS: * We retrospectively evaluated 262 patients submitted from 1998 to 2007
      to prostate re-biopsy (rPBx) after an initial HGPIN diagnosis in tertiary
      academic centres. * HGPIN diagnosis was obtained on initial systematic PBx with
      six to 24 random cores. * All patients were re-biopsied with a 'saturation' rPBx
      with 20-26 cores, with a median time to rPBx of 12 months. * All slides were
      reviewed by expert uropathologists. RESULTS: * Plurifocal HGPIN (pHGPIN) was
      found in 115 patients and monofocal HGPIN (mHGPIN) was found in 147 patients. *
      In total, 108 and 154 patients, respectively, were submitted to >12-core initial
      PBx and <=12-core initial PBx. * Overall PCa detection at rPBx was 31.7%. PSA
      level (7.7 vs 6.6 ng/mL; P= 0.031) and age (68 vs 64 years; P= 0.001) were
      significantly higher in patients with PCa at rPBx. * PCa detection was
      significantly higher in patients with a <=12-core initial PBx than in those with
      a >12-core initial PBx (37.6% vs 23.1%; P= 0.01), as well as in patients with
      pHGPIN than in those with mHGPIN (40% vs 25.1%; P= 0.013). * At multivariable
      analysis, PSA level (P= 0.041; hazards ratio, HR, 1.08), age (P < 0.001; HR,
      1.09), pHGPIN (P= 0.031; HR, 1.97) and <=12-core initial PBx (P= 0.012; HR, 1.95)
      were independent predictors of PCa detection. * A nomogram including these four
      variables achieved 72% accuracy for predicting PCa detection after an initial
      HGPIN diagnosis. CONCLUSIONS: * PCa detection on saturation rPBx after an initial
      diagnosis of HGPIN is significantly higher in patients with a <=12-core initial
      PBx than those with a >12-core initial PBx and in patients with pHGPIN than in
      those with mHGPIN. * We developed a simple prognostic tool for the prediction of
      PCa detection in patients with initial HGPIN diagnosis who were undergoing
      saturation rPBx.

PMID- 21895936
TI  - Suberoylanilide hydroxamic acid (SAHA) combined with bortezomib inhibits renal
      cancer growth by enhancing histone acetylation and protein ubiquitination
      synergistically.
AB  - OBJECTIVE: To investigate the combined effect of two clinically feasible drugs,
      the proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitor
      suberoylanilide hydroxamic acid (SAHA), on human renal cancer cells in vitro and
      in vivo. MATERIALS AND METHODS: The effectiveness of the combination of
      bortezomib (10-20 nm) and SAHA (1-5 um) on renal cancer cells (Caki-1, ACHN, A
      498, 786-O, 769-P) was assessed by MTS assay, colony formation assay, cell cycle
      analysis, and apoptosis assay. In vivo efficacy was evaluated using murine
      subcutaneous (s.c.) tumour models. Protein ubiquitination, unfolded protein
      response, histone acetylation, and changes in the expression of HDAC were
      evaluated by western blotting. RESULTS: The combination of SAHA and bortezomib
      induced apoptosis and inhibited cancer cell proliferation synergistically
      (combination indices <1) and colony formation significantly (P < 0.05). In s.c.
      tumour models a 10-day treatment with a combination of SAHA (50 mg/kg) and
      bortezomib (60 ug/kg) inhibited tumour growth significantly (P < 0.05).
      Mechanistically, SAHA combined with bortezomib enhanced protein ubiquitination
      synergistically and enhanced histone acetylation by inhibiting the expression of
      HDACs. CONCLUSION: SAHA combined with bortezomib inhibits the proliferation of
      renal cancer cells in vitro and in vivo, and the effectiveness of the combination
      is due to its synergistic enhancement of histone acetylation and protein
      ubiquitination.

PMID- 21895938
TI  - Is there a contemporary role for percutaneous needle biopsy in the era of small
      renal masses?
AB  - OBJECTIVE: To evaluate based on the best available data whether there is a
      contemporary role for percutaneous needle biopsy in the era of small renal
      masses. PATIENTS AND METHODS: SRMs are acknowledged to be tumours less than 4cm
      and account for 48%-66% of new kidney cancers. Renal mass biopsy (RMB),
      traditionally limited to specific clinical scenarios and with inherent diagnostic
      accuracy problems has increased in popularity in recent years and is a potential
      valuable tool in the assessment of SRMs. Our discussion focuses on these issues.
      We performed a thorough Medline literature review using a combination of the
      following keywords; small renal mass, renal biopsy, percutaneous renal biopsy,
      renal mass biopsy and renal cell carcinoma. We identified the seminal articles
      with data/information pertaining to renal mass biopsy in small renal masses.
      RESULTS: The facts that 1) a significant number of SRMs are diagnosed in an
      elderly patient cohort, 2) 20% of SRMs are benign on formal histology, 3) there
      are various management strategies now available and 4) modern RMB has a
      diagnostic accuracy >90% with few complications, are all reasons why there has
      been renewed interest in RMB. CONCLUSION:   There is a contemporary role for RMB
      in the era of SRM as the incorporation of molecular profiling of tissue from RMB
      would augment our ability to risk stratify SRMs on an individual patient basis
      and adopt management accordingly. However, clinical judgement is paramount as
      there remains an unpredictable non-negligible risk of disease progression and
      metastasis whilst on surveillance.

PMID- 21895937
TI  - Underestimation of Gleason score at prostate biopsy reflects sampling error in
      lower volume tumours.
AB  - OBJECTIVE: * To determine the influence of tumour and prostate gland volumes on
      the underestimation of prostate cancer Gleason score in diagnostic core biopsies.
      PATIENTS AND METHODS: * Patients undergoing radical prostatectomy with matched
      diagnostic biopsies were identified from a prospectively recorded database. *
      Tumour volumes were measured in serial whole-mount sections with image analysis
      software as part of routine histological assessment. * Differences in various
      metrics of tumour and prostate volume between upgraded tumours and tumours
      concordant for the lower or higher grade were analysed. RESULTS: * In all, 684
      consecutive patients with Gleason score 6 or 7 prostate cancer on diagnostic
      biopsy were identified. * Of 298 patients diagnosed with Gleason 6 tumour on
      biopsy, 201 (67.4%) were upgraded to Gleason 7 or higher on final pathology.
      Similarly, of 262 patients diagnosed with Gleason 3 + 4 = 7 prostate cancer on
      initial biopsy, 60 (22.9%) were upgraded to Gleason score 4 + 3 = 7 or higher. *
      Tumours upgraded from Gleason 6 to 7 had a significantly lower index tumour
      volume (1.73 vs 2 mL, P= 0.029), higher calculated prostate volume (41.6 vs 39
      mL, P= 0.017) and lower relative percentage of tumour to benign glandular tissue
      (4.3% vs 5.9%, P= 0.001) than tumours concordant for the higher grade. *
      Similarly, tumours that were Gleason score 3 + 4 on biopsy and upgraded on final
      pathology to 4 + 3 were significantly smaller as measured by both total tumour
      volume (2.3 vs 3.3 mL, P= 0.005) and index tumour volume (2.2 vs 3, P= 0.027) and
      occupied a smaller percentage of the gland volume (6.3% vs 8.9%, P= 0.017)
      compared with tumours concordant for the higher grade. * On multivariate
      analysis, lower prostate weight (hazard ratio 0.97, 95% confidence interval 0.96
      0.99, P < 0.001) and larger total tumour volume (hazard ratio 1.87, 95%
      confidence interval 1.4-2.6, P < 0.001) independently predicted an upgrade in
      Gleason score from 6 to 7. In tumours upgraded from biopsy Gleason 3 + 4, only
      higher index tumour volume (hazard ratio 3.1, 95% confidence interval 1.01-9.3,
      P= 0.048) was a significant predictor of upgrading on multivariate analysis.
      CONCLUSIONS: * Under-graded tumours are significantly smaller than tumours
      concordant for the higher grade, indicating that incomplete tumour sampling plays
      a significant role in Gleason score assignment error. * Surrogate measures of
      tumour volume may predict those at greatest risk of Gleason score upgrade.

PMID- 21895939
TI  - Comparison of intravesical hyaluronic acid instillation and hyperbaric oxygen in
      the treatment of radiation-induced hemorrhagic cystitis.
AB  - OBJECTIVE: * To compare the efficacy of intravesical hyaluronic acid (HA)
      instillation and hyperbaric oxygen (HBO) in the treatment of radiation-induced
      haemorrhagic cystitis (HC). PATIENTS AND METHODS: * In total 36 patients who
      underwent radiotherapy for their pelvic malignancies and subsequently suffered
      from HC were randomly divided into an HA group and an HBO group. * Symptoms of
      haematuria, frequency of voiding and the visual analogue scale of pelvic pain
      (range 0-10) were evaluated before and after the treatment with follow-up of 18
      months. RESULTS: * All patients completed this study and no obvious side effects
      of intravesical HA were recorded. * The improvement rate showed no statistical
      difference between the two groups at 6, 12 and 18 months after treatment. *
      Decrease of frequency was significant in both groups 6 months after treatment,
      but was only significant in the HA group 12 months after therapy. * The
      improvement in the visual analogue scale remained significant in both groups for
      18 months. CONCLUSIONS: * Intravesical instillation of HA was as effective in
      treating radiation-induced HC as HBO. * It is well tolerated and resulted in a
      sustained decrease of bladder bleeding, pelvic pain and frequency of voiding for
      at least 12 months.

PMID- 21895940
TI  - Open radical prostatectomy in the elderly: a case for concern?
AB  - Study Type--Therapy (case series). Level of Evidence 4. What's known on the
      subject? And what does the study add? Adverse outcomes after radical
      prostatectomy are more often recorded in the elderly. In the USA, elderly
      patients undergoing radical prostatectomy are treated at institutions where
      suboptimal outcomes are recorded. OBJECTIVE: * To assess the rate of adverse
      outcomes after open radical prostatectomy (ORP) in the elderly and to examine the
      effect of annual hospital caseload (AHC) and academic institutional status on
      adverse outcomes in these of patients. PATIENTS AND METHODS: * Within the Health
      Care Utilization Project Nationwide Inpatient Sample, we focused on ORPs
      performed between 1998 and 2007. Subsequently, we restricted to patients aged
      >=75 years. * In both datasets, we examined transfusion rates, intra-operative
      and postoperative complication rates, and in-hospital mortality rates. *
      Stratification was performed according to AHC tertiles and academic status. *
      Multivariable logistic regression analyses were fitted. RESULTS: * Of 115,554 ORP
      patients, 2109 (1.8%) were aged >=75 years. * In multivariable analyses performed
      in the entire cohort, elderly age increased homologous blood transfusion rates (P
      < 0.001), intra-operative (P= 0.001) and postoperative (P < 0.001) complication
      rates, and the mortality rate (P= 0.007). * Most elderly were treated at low or
      intermediate AHC (68.5%) and non-academic centres (56.2%). * Within the elderly
      cohort, intra-operative (2.9%) and postoperative (22.2%) complications tended to
      be highest at low AHC institutions compared to institutions of intermediate (2.7%
      and 17.4%) and high AHC (1.7% and 14.5%). Similarly, intra-operative (2.7% vs
      2.1%) and postoperative complications (19.1% vs 13.9%) tended to be higher at non
      academic than academic centres. * In multivariable analyses performed in the
      elderly subgroup, low AHC predicted higher intra-operative complications and
      higher homologous transfusions, whereas non-academic status predicted higher
      postoperative complications. CONCLUSIONS: * Adverse outcomes are more often
      recorded in the elderly. * Most elderly are treated at institutions where
      suboptimal outcomes are recorded.

PMID- 21895941
TI  - Automatic evaluation of ultrasonography-estimated bladder weight and bladder wall
      thickness in community-dwelling men with presumably normal bladder function.

PMID- 21895942
TI  - Characterization of CpSte11, a MAPKKK gene of Cryphonectria parasitica, and
      initial evidence of its involvement in the pheromone response pathway.
AB  - The gene CpSte11 of Cryphonectria parasitica, which encodes a yeast Ste11
      homologue, was cloned and characterized. Gene replacement analysis revealed a
      high frequency of CpSte11 null mutants. When compared with the wild-type parent
      strain, CpSte11 null mutants showed no difference in terms of growth rate or
      pigmentation. However, CpSte11 null mutants showed a marked decrease in both the
      number and size of stromal pustules on chestnut twigs. The virulence test showed
      that, in comparison with those of the wild-type and virus-infected hypovirulent
      strains, CpSte11 null mutants produced necrotic areas of intermediate size.
      Disruption of the CpSte11 gene also resulted in defects in female fertility. Down
      regulation of transcripts for the mating pheromone precursor gene, Mf2/2, and
      mating response transcription factors, such as cpst12 and pro1, was observed in
      CpSte11 null mutants. The down-regulation of Mf2/2, cpst12 and pro1 was also
      observed in the mutant phenotype of Cpmk2, a mating response Fus3-like mitogen
      activated protein kinase (MAPK) gene, but not in the mutant of Cpmk1, a high
      osmolarity glycerol Hog1-like MAPK gene. These results indicate that the cloned
      CpSte11 gene is functionally involved in the mating response pathway and acts
      through downstream targets, including Cpmk2, cpst12, pro1 and Mf2/2. However, the
      characteristics of the CpSte11 null mutant were fully phenocopied only in the
      cpst12 null mutant, but not in other studied null mutants of components of the
      putative mating response pathway.

PMID- 21895943
TI  - A protease activity-depleted environment for heterologous proteins migrating
      towards the leaf cell apoplast.
AB  - Recombinant proteins face major constraints along the plant cell secretory
      pathway, including proteolytic processing compromising their structural
      integrity. Here, we demonstrate the potential of protease inhibitors as in situ
      stabilizing agents for recombinant proteins migrating towards the leaf apoplast.
      Genomic data for Arabidopsis, rice and Nicotiana spp. were assessed to determine
      the relative incidence of protease families in the cell secretory pathway.
      Transient expression assays with the model platform Nicotiana benthamiana were
      then performed to test the efficiency of protease inhibitors in stabilizing
      proteins targeted to the apoplast. Current genomic data suggest the occurrence of
      proteases from several families along the secretory pathway, including A1 and A22
      Asp proteases; C1A and C13 Cys proteases; and S1, S8 and S10 Ser proteases. In
      vitro protease assays confirmed the presence of various proteases in N.
      benthamiana leaves, notably pointing to the deposition of A1- and S1-type
      activities preferentially in the apoplast. Accordingly, transient expression and
      secretion of the A1/S1 protease inhibitor, tomato cathepsin D inhibitor (SlCDI),
      negatively altered A1 and S1 protease activities in this cell compartment, while
      increasing the leaf apoplast protein content by ~45% and improving the
      accumulation of a murine diagnostic antibody, C5-1, co-secreted in the apoplast.
      SlCYS9, an inhibitor of C1A and C13 Cys proteases, had no impact on the apoplast
      proteases and protein content, but stabilized C5-1 in planta, presumably upstream
      in the secretory pathway. These data confirm, overall, the potential of protease
      inhibitors for the in situ protection of recombinant proteins along the plant
      cell secretory pathway.

PMID- 21895944
TI  - Resistance to Wheat streak mosaic virus generated by expression of an artificial
      polycistronic microRNA in wheat.
AB  - Wheat streak mosaic virus (WSMV) is a persistent threat to wheat production,
      necessitating novel approaches for protection. We developed an artificial miRNA
      strategy against WSMV, incorporating five amiRNAs within one polycistronic amiRNA
      precursor. Using miRNA sequence and folding rules, we chose five amiRNAs
      targeting conserved regions of WSMV but avoiding off-targets in wheat. These
      replaced the natural miRNA in each of five arms of the polycistronic rice miR395,
      producing amiRNA precursor, FanGuard (FGmiR395), which was transformed into wheat
      behind a constitutive promoter. Splinted ligation detected all five amiRNAs being
      processed in transgenic leaves. Resistance was assessed over two generations.
      Three types of response were observed in T(1)  plants of different transgenic
      families: completely immune; initially resistant with resistance breaking down
      over time; and initially susceptible followed by plant recovery. Deep sequencing
      of small RNAs from inoculated leaves allowed the virus sequence to be assembled
      from an immune transgenic, susceptible transgenic, and susceptible non-transgenic
      plant; the amiRNA targets were fully conserved in all three isolates, indicating
      virus replication on some transgenics was not a result of mutational escape by
      the virus. For resistant families, the resistance segregated with the transgene.
      Analysis in the T(2)  generation confirmed the inheritance of immunity and gave
      further insights into the other phenotypes. Stable resistant lines developed no
      symptoms and no virus by ELISA; this resistance was classified as immunity when
      extracts failed to transmit from inoculated leaves to test plants. This study
      demonstrates the utility of a polycistronic amiRNA strategy in wheat against
      WSMV.

PMID- 21895945
TI  - Enhanced seed viability and lipid compositional changes during natural ageing by
      suppressing phospholipase Dalpha in soybean seed.
AB  - Changes in phospholipid composition and consequent loss of membrane integrity are
      correlated with loss of seed viability. Furthermore, phospholipid compositional
      changes affect the composition of the triacylglycerols (TAG), i.e. the storage
      lipids. Phospholipase D (PLD) catalyses the hydrolysis of phospholipids to
      phosphatidic acid, and PLDalpha is an abundant PLD isoform. Although wild-type
      (WT) seeds stored for 33 months were non-viable, 30%-50% of PLDalpha-knockdown
      (PLD-KD) soybean seeds stored for 33 months germinated. WT and PLD-KD seeds
      increased in lysophospholipid levels and in TAG fatty acid unsaturation during
      ageing, but the levels of lysophospholipids increased more in WT than in PLD-KD
      seeds. The loss of viability of WT seeds was correlated with alterations in
      ultrastructure, including detachment of the plasma membrane from the cell wall
      complex and disorganization of oil bodies. The data demonstrate that, during
      natural ageing, PLDalpha affects the soybean phospholipid profile and the TAG
      profile. Suppression of PLD activity in soybean seed has potential for improving
      seed quality during long-term storage.

PMID- 21895946
TI  - Field performance of transgenic sugarcane expressing isomaltulose synthase.
AB  - Transgenic sugarcane plants expressing a vacuole-targeted isomaltulose (IM)
      synthase in seven recipient genotypes (elite cultivars) were evaluated over 3
      years at a field site typical of commercial cane growing conditions in the
      Burdekin district of Australia. IM concentration typically increased with
      internode maturity and comprised up to 217 mm (33% of total sugars) in whole-cane
      juice. There was generally a comparable decrease in sucrose concentration, with
      no overall decrease in total sugars. Sugarcane is vegetatively propagated from
      stem cuttings known as setts. Culture-derived plants were slower to establish and
      generally gave shorter and thinner stalks at harvest than those grown from field
      sourced setts in the initial field generations. However, after several cycles of
      field propagation, selections were obtained with cane yields similar to the
      recipient genotypes. There was no apparent adverse effect of IM accumulation on
      vigour assessed by stalk height and diameter or other visual indicators including
      germination of setts and establishment of stools. There was some inconsistency in
      IM levels in juice, between samplings of the vegetatively propagated transgenic
      lines. Until the causes are resolved, it is prudent to selectively propagate from
      stalks with higher IM levels in the initial vegetative field generations.
      Pol/Brix ratio allowed rapid identification of lines with high IM levels, using
      common sugar industry instruments. Sucrose isomerase activity was low in these
      transgenic lines, and the results indicate strong potential to develop sugarcane
      for commercial-scale production of IM if higher activity can be engineered in
      appropriate developmental patterns.

PMID- 21895947
TI  - The effect of an antenatal physical exercise programme on maternal/perinatal
      outcomes and quality of life in overweight and obese pregnant women: a randomised
      clinical trial.
AB  - OBJECTIVE: To evaluate the effectiveness and safety of physical exercise in terms
      of maternal/perinatal outcomes and the perception of quality of life (QoL) in
      pregnant obese and overweight women. DESIGN: A randomised controlled clinical
      trial. SETTING: The Prenatal Outpatient Clinic of the Women's Integral Healthcare
      Centre (CAISM-UNICAMP) at the University of Campinas, Campinas, Brazil.
      POPULATION: Eighty-two pregnant women (age >= 18 years; pre-gestational body mass
      index >= 26 kg/m(2) ; gestational age 14-24 weeks). METHODS: Women were
      randomised into two groups: women in one group exercised under supervision and
      received home exercise counselling (the 'study group'; n = 40) and women in the
      other group followed the routine prenatal care programme (the 'control group'; n
      = 42). MAIN OUTCOME MEASURES: Primary outcomes were gestational weight gain
      during the programme and excessive maternal weight gain. Secondary outcomes were
      increased arterial blood pressure, perinatal outcomes and QoL (WHOQOL-BREF).
      RESULTS: In the study group, 47% of pregnant women had weight gains above the
      recommended limit, compared with 57% of women in the control group (P = 0.43).
      There was no difference in gestational weight gain between the groups. Overweight
      pregnant women who exercised gained less weight during the entire pregnancy (10.0
      +/- 1.7 kg versus 16.4 +/- 3.9 kg, respectively; P = 0.001) and after entry into
      the study (5.9 +/- 4.3 kg versus 11.9 +/- 1.5 kg, respectively; P = 0.021)
      compared with women in the control group. Arterial blood pressure was similar
      between the groups over time. There was no difference in perinatal outcome or
      QoL. CONCLUSIONS: The exercise programme was not associated with control of
      gestational weight gain in our sample as a whole, but was beneficial for lower
      gestational weight gain in overweight women. Exercise was not associated with
      adverse perinatal outcomes and did not affect variation in arterial blood
      pressure or the perception of QoL.

PMID- 21895951
TI  - Trends in obstetric practices and meconium aspiration syndrome: a population
      based study.
AB  - OBJECTIVE: To determine trends in the incidence of meconium aspiration syndrome
      (MAS), and maternal factors and obstetric practices associated with any decline.
      DESIGN: Population-based cohort study. SETTING: New South Wales (NSW), Australia.
      POPULATION: All 877 037 liveborn, singleton, term infants (>= 37 weeks of
      gestation) in the period 1997-2007. METHODS: Data were obtained from birth
      records linked to the neonatal hospital discharge records. The birth data
      provided information on maternal and obstetric factors, whereas the outcome of
      interest, MAS, was obtained from hospital data on the neonates. Multivariable
      logistic regression was used to estimate the risk of MAS while simultaneously
      adjusting for the explanatory variables. MAIN OUTCOME MEASURES: The incidence of
      MAS per 1000 births, and odds ratios and 95% confidence intervals for maternal
      and obstetric factors for the development of MAS. RESULTS: The incidence of MAS
      declined significantly by 11.3% per annum (95% CI 10.1-12.6; P < 0.001) from 4.1
      per 1000 births in 1997 to 1.3 per 1000 births in 2007. This was associated with
      a statistically significant decline in risk factors: maternal smoking (from 20 to
      12%), gestational age (from 57 to 47% >= 40 weeks of gestation), delivery at
      small hospitals (from 15 to 9%) and infants with birthweight below the third
      percentile (from 3.3 to 2.4%). There were simultaneous statistically significant
      increases in practices that reduce the risk of MAS: labour inductions (from 22 to
      27%) and birth by caesarean section, both elective, prior to 40 weeks of
      gestation (from 7.3 to 13.8%), and emergency (from 3.0 to 5.3% prior to 40 weeks
      of gestation, and from 5.1 to 6.7% at 40 weeks of gestation or later).
      CONCLUSIONS: The rate of MAS is declining, and this decline is associated with a
      reduction in maternal and pregnancy risk factors, and an increase in protective
      obstetric practices.

PMID- 21895948
TI  - Regeneration of cervix after excisional treatment for cervical intraepithelial
      neoplasia: a study of collagen distribution.
AB  - OBJECTIVE: To study the distribution of collagen in the regenerated cervical
      tissue after excisional treatment for cervical intraepithelial neoplasia (CIN).
      DESIGN: Cohort study. SETTING: A large tertiary teaching hospital in London.
      POPULATION: Women who underwent repeat excisional treatment for treatment failure
      or persistent CIN. METHODS: Eligible women who underwent a repeat excisional
      treatment for treatment failure, including hysterectomy, between January 2002 and
      December 2007 in our colposcopy unit were identified by the Infoflex((r))
      database and SNOMED encoded histopathology database. Collagen expression was
      assessed using picro-Sirius red stain and the intensity of staining was compared
      in paired specimens from the first and second treatments. MAIN OUTCOME MEASURE:
      Differences in collagen expression were examined in the paired excisional
      treatment specimens. RESULTS: A total of 17 women were included. Increased
      collagen expression in the regenerated cervical tissue of the second cone
      compared with the first cone was noted in six women, decreased expression was
      noted in five women, and the pattern of collagen distribution was equivocal in
      six women. CONCLUSION: There is no overall change in collagen distribution during
      regeneration following excisional treatment for CIN.

PMID- 21895949
TI  - Perioperative outcomes using LigaSure compared with conventional bipolar
      instruments in laparoscopic hysterectomy: a randomised controlled trial.
AB  - OBJECTIVE: To compare the effects of LigaSure versus the conventional bipolar
      technique on operating time and blood loss during laparoscopic hysterectomy.
      DESIGN: A randomised controlled trial. SETTING: Three teaching hospitals.
      POPULATION: Women undergoing a laparoscopic hysterectomy for benign indications.
      METHODS: 140 women undergoing a laparoscopic hysterectomy were randomised for
      LigaSure or conventional bipolar instruments. MAIN OUTCOME MEASURES: Primary
      outcome was operating time from initial skin incision till detachment of the
      uterus. Secondary outcome measures were total operating time (from initial skin
      incision till final skin closure), time to dissect the adnexal ligaments, intra
      operative blood loss and subjective evaluation by the surgeon of the instrument
      used. RESULTS: No differences in operating time (from initial skin incision till
      uterine detachment and initial skin incision till final skin closure) using
      LigaSure versus conventional bipolar instruments: 97.6 versus 91.8 minutes (P =
      0.39, 95% CI - 7.6 to 19.2), and 148.1 versus 142.1 minutes (P = 0.46, 95% CI -
      10.1 to 22.3), respectively. The mean blood loss using LigaSure versus
      conventional bipolar was 234.1 versus 273.1 ml (P = 0.46, 95% CI -39.1 to 52.7).
      Various subjective efficacy and instrument handling parameters were significantly
      different between the two instruments and between the different participating
      centres. CONCLUSIONS There were no significant differences in operating time and
      blood loss between the use of LigaSure and the use of conventional bipolar
      instruments during laparoscopic hysterectomy, even after correction for potential
      confounders. User satisfaction parameters were assessed as significantly
      different by surgeons of the participating centres.

PMID- 21895950
TI  - Multidisciplinary convalescence recommendations after gynaecological surgery: a
      modified Delphi method among experts.
AB  - OBJECTIVE: To generate structured detailed uniform convalescence recommendations
      after gynaecological surgery by a modified Delphi method amongst experts and a
      representative group of physicians. DESIGN: Modified Delphi study. SETTING:
      Expert physicians recruited by their respective medical boards and employed at
      different hospitals, doctor's surgeries and healthcare services. POPULATION:
      Twelve experts (five gynaecologists, two general practitioners [GPs] and five
      occupational physicians [OPs]) and a representative sample of 63 medical doctors.
      METHODS: Multidisciplinary detailed recommendations for graded resumption of
      relevant activities after uncomplicated hysterectomy (laparoscopic supracervical,
      total laparoscopic/laparoscopic-assisted, vaginal and abdominal hysterectomies)
      and laparoscopic adnexal surgery were developed. Recommendations were based on a
      literature review and a modified Delphi procedure among 12 experts, recruited in
      collaboration with the participating medical boards of gynaecologists, GPs and
      OPs. MAIN OUTCOME MEASURES: A multidisciplinary consensus of at least 67% on the
      relevant detailed convalescence recommendations in relation to hysterectomy and
      laparoscopic adnexal surgery. RESULTS: Out of initially 65 activities, the expert
      panel judged 38 activities relevant for convalescence recommendations. Consensus
      for all activities was achieved after four Delphi rounds and two group
      discussions. The recommendations were judged as feasible by a representative
      sample of 26 gynaecologists, 19 GPs and 18 OPs. CONCLUSIONS: Consensus between
      gynaecologists, GPs and OPs was achieved on all relevant convalescence
      recommendations regarding hysterectomy (abdominal, vaginal and laparoscopic) and
      laparoscopic adnexal surgery.

PMID- 21895952
TI  - A pro forma and review process for the assessment of standards of care in
      stillbirths.
AB  - Stillbirth rates do not address deficiencies in care. We collected information on
      stillbirths from 2004 to 2009 using a standardised pro forma. A local panel used
      the pro forma to grade the level of care received by the Confidential Enquiry
      into Stillbirths and Deaths in Infancy (CESDI) categorisation. Comparison using
      kappa scores showed agreement between local and external multidisciplinary panels
      of similar referral patterns (n = 47, kappa = 0.7), and that the categorisation
      was unaffected by the individual who fills out the pro forma (n = 17, kappa =
      0.5). There was less agreement between the local panel and adverse event review
      (n = 100, kappa = 0.45). This report represents a validation of the pro forma and
      the review process for standard use in all units.

PMID- 21895953
TI  - Age at menarche and pelvic girdle syndrome in pregnancy: a population study of 74
      973 women.
AB  - OBJECTIVE: To study the association of age at menarche with presence of pelvic
      girdle syndrome in pregnancy. DESIGN: Population study. SETTING: Norway 1999
      2007. POPULATION: A total of 74 973 pregnant women in the Norwegian Mother and
      Child Cohort Study. METHODS: Data were obtained by self-administered
      questionnaires in weeks 17 and 30 of gestation. MAIN OUTCOME MEASURE: Pelvic
      girdle syndrome in pregnancy at 30 weeks of gestation, defined as pain in the
      pubic symphysis in the anterior pelvis and in both sacroiliac joints in the
      posterior pelvis. RESULTS: The prevalence of pelvic girdle syndrome was 20.6%
      (328/1593) in women with menarche before the age of 11, it was 16.3% (3200/22
      044) in women with menarche at the age of 12 and 12.7% (1252/9859) in women with
      menarche after the age of 14 (chi-square test for trend, P < 0.001). The inverse
      association of age at menarche with pelvic girdle syndrome remained after
      adjustment for body mass index, maternal age, parity, educational level, previous
      low back pain, emotional distress and physically demanding work. Women with early
      menarche and high body mass index had the highest prevalence of pelvic girdle
      syndrome, but the association of early menarche with pelvic girdle syndrome was
      similar in women with and without high body mass index. CONCLUSIONS: Early
      menarche was associated with increased prevalence of pelvic girdle syndrome in
      pregnancy. Factors associated with early menarche may play a role in the
      development of pelvic girdle pain.

PMID- 21895954
TI  - To what extent are national guidelines for the management of urinary incontinence
      in women adhered? Data from a national audit.
AB  - OBJECTIVE  To assess the degree of adherence to the current National Institute
      for Health and Clinical Excellence (NICE) guidelines on the management of urinary
      incontinence (UI) in women. DESIGN: Retrospective survey of consecutive female
      inpatients and outpatients with UI as part of a national audit. SETTING: NHS
      hospital and primary care (PC) trusts. POPULATION OR SAMPLE: Twenty-five women
      <65 years old and 25 women >= 65 years old from each participating site. METHOD:
      All NHS trusts in England, Wales and Northern Ireland were eligible to
      participate. A web-based data collection form aligned to the NICE guidelines was
      constructed for the study. All data submitted to the audit were anonymous and
      access to the web-tool was password-protected for confidentiality. RESULTS: Data
      were returned by 128 acute and 75 PC trusts on 7846 women. No diagnosis was
      documented in 6.8% (153/2254) of younger and 28% (571/2011) of older women in
      hospitals (P < 0.001), and by 8.6% (123/1435) of younger and 21% (380/1786) of
      older women in PC trusts. In hospitals, 26% (396/1524) of younger women and 15%
      (182/1231) of older women (P < 0.001) and in PC trusts 8.2% (77/934) of younger
      and 4.7% (46/975) of older women underwent multichannel cystometry before
      conservative therapy. Documentation of discussion of causes and treatment of UI
      occurred in 76% (1717/2254) of younger and 44% (884/2011) of older women in
      hospitals (P < 0.001) and in 75% (1080/1435) of younger and 53% (948/1786) of
      older women in PC trusts (P < 0.001). CONCLUSION Older women are less likely to
      receive NICE compliant management. Adherence varies according to recommendation.
      There needs to be concentration on evidence-based community provision of care by
      competent and interested clinicians before the aims of the NICE guidelines are
      met.

PMID- 21895955
TI  - Delayed blastocyst development does not influence the outcome of frozen-thawed
      transfer cycles.
AB  - OBJECTIVE: To compare the outcome of transfer of thawed blastocysts frozen on
      either day 5 or day 6 after in vitro fertilisation. DESIGN: Cohort observational
      study. SETTING: Tertiary assisted conception unit in London, UK. POPULATION: Six
      hundred and forty-two consecutive nondonor programmed thawed blastocyst transfer
      (TBT) cycles. METHODS: High-grade blastocysts were frozen on day 5 (n = 314) or
      day 6 (n = 328) after fertilisation using a slow-freezing protocol. Endometrial
      preparation was performed using estradiol valerate. Progesterone supplementation
      was commenced when the endometrial thickness had reached 7 mm or more. Frozen
      blastocysts were thawed on day 6 of progesterone supplementation and assessed
      immediately after thawing for survival, and after 3-4 hours for blastocoele re
      expansion. Main outcome measures Thawed blastocyst survival and re-expansion
      rates, and pregnancy and live birth rates, per TBT. RESULTS: Thawed blastocyst
      survival and re-expansion rates were comparable between the day 5 and day 6
      groups (87% versus 87%, P = 0.50 and 73% versus 71%, P = 0.35, respectively). The
      live birth rate was similar between the two groups (29% versus 28.5%, P = 0.93,
      respectively). After adjusting for confounding variables, the odds ratio (OR) of
      a live birth in cycles in which the thawed blastocysts were frozen on day 6
      compared with day 5 was 1.23 [95% confidence interval (CI), 0.81-1.86, P = 0.34].
      CONCLUSION: The pregnancy potential of high-grade blastocysts frozen on day 5 and
      day 6 after in vitro fertilisation and replaced in programmed TBT cycles is
      comparable.

PMID- 21895957
TI  - The natural history of pregnancy: diseases of early and late gestation.
AB  - OBJECTIVE: To identify the disease processes underlying the increasing rate of
      gestational age-specific perinatal mortality observed under the fetuses-at-risk
      model. DESIGN: Retrospective cohort study. SETTING: USA and Nova Scotia, Canada.
      POPULATION: Births in the USA (1995 and 2005) and Nova Scotia, Canada (1988
      2007). METHODS: Incidence rates of perinatal death and serious neonatal morbidity
      were calculated using the fetuses-at-risk approach (e.g. cumulative incidence of
      stillbirth during any gestational week per 1000 fetuses at risk of stillbirth).
      MAIN OUTCOME MEASURES: Perinatal mortality and serious neonatal morbidity.
      RESULTS: Perinatal mortality rates increased with advancing gestation. Rates of
      bronchopulmonary dysplasia, intraventricular haemorrhage, periventricular
      leucomalacia and retinopathy of prematurity were highest in early gestation,
      whereas rates of meconium aspiration syndrome and aspiration pneumonitis were
      highest at late term and post-term gestation. Respiratory depression (i.e. delay
      in initiating and maintaining respiration after birth, low 5-minute Apgar score
      or seizures caused by neonatal encephalopathy) showed an increase from 34 weeks
      onwards. The increase in perinatal mortality rates at late gestation was
      congruent with increases in respiratory depression. Other findings included a
      high incidence of respiratory distress syndrome at late gestation, a nonspecific
      pattern in the gestational age-specific rates of necrotising enterocolitis and
      high rates of sudden infant death syndrome at late gestation. CONCLUSIONS: The
      natural history of pregnancy is characterised by diseases of early and late
      gestation, with the latter largely determining patterns of gestational age
      specific perinatal mortality. These findings have implications for obstetric
      theory and provide insight into various contemporary phenomena, including the
      rise in iatrogenic late preterm birth.

PMID- 21895956
TI  - Can visual cervical screening be sustained in routine health services? Experience
      from Mali, Africa.
AB  - OBJECTIVE: To assess the feasibility of sustaining visual cervical screening and
      treatment services in Mali, and to evaluate their performance and impact in
      improving the provision of cervical cancer control, following an initial cross
      sectional study. DESIGN: Descriptive study. SETTING: Bamako area, Mali.
      POPULATION: Women aged 30-59 years. METHODS: Routine visual screening and
      treatment services were organised through two hospitals and 14 health centres.
      Patients with positive visual screening tests underwent colposcopy and/or
      directed biopsies, and ablative or surgical excision treatment was offered to
      those with cervical intraepithelial neoplasia (CIN). MAIN OUTCOME MEASURES: Test
      positivity, detection and treatment rates for CIN and the sustainability of
      screening services. RESULTS: Of the 14,141 women screened, 1682 (11.9%) were
      positive and were referred for further investigations and treatment. Over 75% of
      the screen-positive women underwent colposcopy and/or biopsy. CIN 1 was detected
      in 383 women, CIN 2 in 88, CIN 3 in 37 and invasive cervical cancer in 497. More
      than 80% of women with CIN and 35% of those with invasive cancer received
      treatment. The test performance characteristics and treatment coverage of routine
      screening were similar to those observed in the preceding cross-sectional study.
      CONCLUSION: Visual screening and treatment services are sustainable and effective
      in improving cervical cancer control provision by health services in Bamako,
      Mali. It is essential to organise and sustain several point-of-care services in
      order to extend cervical cancer prevention in low-income African countries.

PMID- 21895959
TI  - What women want. Women's preferences for the management of low-grade abnormal
      cervical screening tests: a systematic review.
AB  - BACKGROUND: If human papillomavirus (HPV) testing will replace cytology in
      primary cervical screening, the frequency of low-grade abnormal screening tests
      will double. Several available alternatives for the follow-up of low-grade
      abnormal screening tests have similar outcomes. In this situation, women's
      preferences have been proposed as a guide for management decisions. OBJECTIVES:
      To determine women's preferences for the follow-up of low-grade cervical
      screening abnormalities. SEARCH STRATEGY: Using Medical Subject Headings (MeSH)
      terms, PubMed was searched for articles published up to December 2010. The
      reference lists of the retrieved studies were consulted. SELECTION CRITERIA:
      Studies asking women to state a preference between active follow-up and
      observation for the management of low-grade abnormalities on screening cytology
      or HPV tests. DATA COLLECTION AND ANALYSIS: Information on study design,
      participants and outcomes was retrieved using a prespecified form. Studies were
      sorted by design. MAIN RESULTS: Thirteen studies were included in the review. In
      all five studies that surveyed women with abnormal tests before any management
      had started, two-thirds preferred active follow-up, predominantly as immediate
      colposcopy, to observation, predominantly as repeated Pap smears. In all but two
      studies testing other situations, women more often expressed a preference for
      active follow-up than for observation; however, women appeared to be somewhat
      more willing to accept observation if reassured of the low risk of cervical
      cancer. CONCLUSIONS: Even for low-grade abnormal cervical tests, women tend to
      prefer active management strategies. It may be a challenge to meet their
      expectations of optimal follow-up when HPV testing is used in primary screening.

PMID- 21895958
TI  - Intra-operative frozen section analysis for suspected early-stage ovarian cancer:
      11 years of Gateshead Cancer Centre experience.
AB  - OBJECTIVE: In centres in which intra-operative frozen section (FS) analysis is
      not performed, 'apparent' early-stage ovarian cancer diagnosed after surgery on
      paraffin section may require further restaging laparotomy or adjuvant
      chemotherapy. Previous studies on FS analysis have reported high sensitivity,
      specificity and overall accuracy. The objective of this article is to present the
      largest published dataset on the accuracy of FS analysis over an 11-year period
      from a single institution. DESIGN: Diagnostic test accuracy. SETTING: Northern
      Gynaecological Oncology Centre and Department of Cellular Pathology, Gateshead,
      UK. POPULATION: 1439 intra-operative FS analyses performed between January 2000
      and December 2010 for suspected ovarian cancer. METHODS: Prospectively collected
      data on FS analysis were compared with gold standard paraffin section. MAIN
      OUTCOME MEASURES: Sensitivity, specificity, likelihood ratios and post-test
      probability. RESULTS: The overall sensitivity and specificity of FS analysis were
      91.2% and 98.6%, respectively. Positive and negative likelihood ratios were 64.7%
      and 0.09%, respectively. The pre-test probability of an ovarian tumour being
      borderline or malignant was 45.8%. When FS analysis was reported to be positive,
      the post-test probability increased to 98% (confidence interval, 97-99%).
      Conversely, when FS analysis was reported to be negative, the post-test
      probability decreased to 7% (confidence interval, 6-9%). The majority of false
      test results were either borderline tumours or of mucinous differentiation.
      CONCLUSIONS: Intra-operative FS analysis has excellent diagnostic test accuracy
      and assists gynaecological oncologists to perform the appropriate surgery in 95%
      of cases, thereby preventing the morbidity of surgical staging in benign cases
      and the morbidity of restaging procedures or chemotherapy in early-stage
      malignant tumours.

PMID- 21895960
TI  - Decline in betahCG levels between days 0 and 4 after a single dose of
      methotrexate for ectopic pregnancy predicts treatment success: a retrospective
      cohort study.
AB  - In current protocols for the medical management of ectopic pregnancies, the first
      indication of treatment response is obtained no sooner than day 7. We examined
      whether human chorionic gonadotrophin (betahCG) trends between days 0 and 4 after
      methotrexate provide an earlier indication of the likely outcome. Of 33 patients
      where serum betahCG dropped between days 0 and 4 after methotrexate, the ectopic
      pregnancy was resolved in 88% of cases without further treatment. Of 12 women
      where serum betahCG rose between days 0 and 4, only 42% had treatment success. A
      fall in betahCG between days 0 and 4 after treatment with methotrexate for
      ectopic pregnancy predicts a high likelihood of treatment success.

PMID- 21895962
TI  - Increased tissue factor pathway inhibitor activity is associated with myocardial
      infarction in young women: results from the RATIO study.
AB  - BACKGROUND: The tissue factor pathway inhibitor (TFPI)/protein S anticoagulant
      system is a potent inhibitor of blood coagulation. TFPI and protein S are major
      determinants of thrombin generation (TG) tests determined at low tissue factor
      (TF) and at high TF concentrations in the presence of activated protein C (APC).
      Both TFPI and protein S protect against venous thrombosis, but the importance of
      the TFPI/protein S system in arterial thrombosis remains unclear. OBJECTIVES: To
      investigate the influence of the TFPI/protein S anticoagulant system on the risk
      of myocardial infarction (MI) in young women. METHODS: The RATIO study is a case
      control study in women under 50 years of age, including 205 patients and 638
      controls. TFPI and protein S were quantified using ELISA. The TFPI/protein S
      activity (nTFPIr) and the APC sensitivity ratio (nAPCsr) were determined using TG
      tests. Odds ratios (ORs) adjusted for putative confounders and corresponding 95%
      confidence intervals (95% CI) were determined. RESULTS: Women with MI had higher
      TFPI levels than controls (135.9 +/- 40% vs. 124.2 +/- 41%), resulting in
      increased TFPI/protein S activities and increased APC sensitivity. Furthermore,
      an increased TFPI activity was associated with MI [nTFPIr: adjusted OR Q1 vs. Q4
      = 2.1 (95%CI 1.1-4.1)]. Additionally, an increased APC sensitivity was associated
      with MI [nAPCsr: adjusted OR Q1 vs. Q4 = 1.7 (95% CI 0.9-3.2)] CONCLUSION: Women
      with MI had increased TFPI levels compared with controls. Consequently, the
      TFPI/protein S activity and APC sensitivity are increased in women with MI.
      Whether this increase in TFPI activity acts as a compensating mechanism for an
      increased procoagulant state or is a marker of endothelial damage remains to be
      investigated.

PMID- 21895964
TI  - Elevation of IGF-2 receptor and the possible underlying implications in end-stage
      heart failure patients before and after heart transplantation.
AB  - Up-regulation of insulin-like growth factor 2 receptor (IGF-2R) involved in
      angiotensin II-induced cell apoptosis in cardiomyoblasts, and correlated with
      cardiomyocyte apoptosis in hypertensive rat hearts. Here, we detected IGF-2R
      levels and explored the possible underlying implications in end-stage heart
      failure (HF) patients before and after heart transplantation. Western blot and
      immunohistochemistry were used to measure cardiac IGF-2R levels. ELISA was used
      to detect serum IGF-2R and CD8 levels. Labelling of DNA strand breaks and
      dihydroethidium detection were used to determine cellular apoptosis and reactive
      oxygen species, respectively. Cardiac IGF-2R levels increased in end-stage HF
      patients (n = 11) compared with non-failing control subjects. Leu27-IGF-2, an IGF
      2 analogue to activate specially the IGF-2R, could induce apoptosis and reactive
      oxygen species production in neonatal rat ventricular myocytes. The serum IGF-2R
      levels were significantly higher in HF patients than those in non-failing control
      subjects. An unexpected observation is that the serum IGF-2R levels further
      increased after heart transplantation, peaked at the first month, and gradually
      reduced close to the levels before heart transplantation at the 6th months after
      heart transplantation. Serum CD8, a marker of acute rejection, had no change
      after heart transplantation, but IGF-2R and Granzyme B, as a ligand for the IGF
      2R and a marker for CD8 T lymphocyte activation, coexisted in the transplanted
      hearts. Our preliminary studies suggest that elevation of IGF-2R may participate
      in pathological process of end-stage HF and involved in the acute cellular
      rejection after heart transplantation.

PMID- 21895963
TI  - PED/PEA-15 interacts with the 67 kD laminin receptor and regulates cell adhesion,
      migration, proliferation and apoptosis.
AB  - Phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes-15 kD
      (PED/PEA-15) is an anti-apoptotic protein whose expression is increased in
      several human cancers. In addition to apoptosis, PED/PEA-15 is involved in the
      regulation of other major cellular functions, including cell adhesion, migration,
      proliferation and glucose metabolism. To further understand the functions of this
      protein, we performed a yeast two-hybrid screening using PED/PEA-15 as a bait and
      identified the 67 kD high-affinity laminin receptor (67LR) as an interacting
      partner. 67 kD laminin receptor is a non-integrin cell-surface receptor for the
      extracellular matrix (ECM), derived from the dimerization of a 37 kD cytosolic
      precursor (37LRP). The 67LR is highly expressed in human cancers and widely
      recognized as a molecular marker of metastatic aggressiveness. The molecular
      interaction of PED/PEA-15 with 67LR was confirmed by pull-down experiments with
      recombinant His-tagged 37LRP on lysates of PED/PEA-15 transfected HEK-293 cells.
      Further, overexpressed or endogenous PED/PEA-15 was co-immunoprecipitated with
      67LR in PED/PEA-15-transfected HEK-293 cells and in U-373 glioblastoma cells,
      respectively. PED/PEA-15 overexpression significantly increased 67LR-mediated HEK
      293 cell adhesion and migration to laminin that, in turn, determined PED/PEA-15
      phosphorylation both in Ser-104 and Ser-116, thus enabling cell proliferation and
      resistance to apoptosis. PED/PEA-15 ability to induce cell responses to ECM
      derived signals through interaction with 67LR may be of crucial importance for
      tumour cell survival in a poor microenvironment, thus favouring the metastatic
      spread and colonization.

PMID- 21895965
TI  - Immune response to human embryonic stem cell-derived cardiac progenitors and
      adipose-derived stromal cells.
AB  - Transplantation of allogeneic human embryonic stem cell-derived cardiac
      progenitors triggers an immune response. We assessed whether this response could
      be modulated by the concomitant use of adipose-derived stromal cells (ADSC).
      Peripheral blood mononuclear cells were collected from 40 patients with coronary
      artery disease (CAD) and nine healthy controls. Cardiac progenitors (CD15(+)
      Mesp1(+)) were generated as already reported from the I6 cell line treated with
      bone morphogenetic protein (BMP)-2. Adipose-derived stromal cells were obtained
      from abdominal dermolipectomies. We assessed the proliferative response of
      peripheral lymphocytes from patients and controls to cardiac progenitors cultured
      on a monolayer of ADSC, to allogeneic lymphocytes in mixed lymphocyte culture and
      to the T cell mitogen phytohemaglutin A in presence or absence of ADSC. Cardiac
      progenitors cultured on a monolayer of ADSC triggered a proliferation of
      lymphocytes from both patients and controls albeit lower than that induced by
      allogeneic lymphocytes. When cultured alone, ADSC did not induce any
      proliferation of allogeneic lymphocytes. When added to cultures of lymphocytes,
      ADSC significantly inhibited the alloantigen or mitogen-induced proliferative
      response. Compared to healthy controls, lymphocytes from patients presenting CAD
      expressed a decreased proliferative capacity, in particular to mitogen-induced
      stimulation. Adipose-derived stromal cells express an immunomodulatory effect
      that limits both alloantigen and mitogen-induced lymphocyte responses.
      Furthermore, lymphocytes from patients with CAD are low responders to
      conventional stimuli, possibly because of their age and disease-associated
      treatment regimens. We propose that, in combination, these factors may limit the
      in vivo immunogenicity of cardiac progenitors co-implanted with ADSC in patients
      with CAD.

PMID- 21895969
TI  - Will mineral trioxide aggregate replace calcium hydroxide in treating pulpal and
      periodontal healing complications subsequent to dental trauma? A review.
AB  - Mineral trioxide aggregate (MTA) has over the last two decades begun to take the
      place of calcium hydroxide (CH) in the treatment of a variety of pulpal and
      periodontal healing complications following dental trauma. These conditions
      include teeth with: (i) exposed pulps, (ii) immature roots and pulp necrosis,
      (iii) root fractures and pulp necrosis located in the coronal part of the pulps,
      and (iv) external infection-related (inflammatory) root resorption. The main
      reasons for replacing CH with MTA in these situations have generally been the
      delayed effect when using CH to induce hard tissues, the quality of such induced
      hard tissues, and finally the dentin weakening effect of CH, which in some
      instances lead to cervical root fractures in immature teeth. MTA appears, from a
      relatively few clinical studies, to overcome these shortcomings of CH. The lack
      of long-term clinical studies, however, may warrant a certain reservation in an
      unrestricted replacement of CH with MTA. A definite need for randomized clinical
      studies comparing CH and MTA in trauma healing situations is urgently needed.

PMID- 21895967
TI  - Molecular mechanisms controlling CFTR gene expression in the airway.
AB  - The low levels of CFTR gene expression and paucity of CFTR protein in human
      airway epithelial cells are not easily reconciled with the pivotal role of the
      lung in cystic fibrosis pathology. Previous data suggested that the regulatory
      mechanisms controlling CFTR gene expression might be different in airway
      epithelium in comparison to intestinal epithelium where CFTR mRNA and protein is
      much more abundant. Here we examine chromatin structure and modification across
      the CFTR locus in primary human tracheal (HTE) and bronchial (NHBE) epithelial
      cells and airway cell lines including 16HBE14o- and Calu3. We identify regions of
      open chromatin that appear selective for primary airway epithelial cells and show
      that several of these are enriched for a histone modification (H3K4me1) that is
      characteristic of enhancers. Consistent with these observations, three of these
      sites encompass elements that have cooperative enhancer function in reporter gene
      assays in 16HBE14o- cells. Finally, we use chromosome conformation capture (3C)
      to examine the three-dimensional structure of nearly 800 kb of chromosome 7
      encompassing CFTR and observe long-range interactions between the CFTR promoter
      and regions far outside the locus in cell types that express high levels of CFTR.

PMID- 21895968
TI  - Experimental acute myocardial infarction: telocytes involvement in neo
      angiogenesis.
AB  - We used rat experimental myocardial infarction to study the ultrastructural
      recovery, especially neo-angiogenesis in the infarction border zone. We were
      interested in the possible role(s) of telocytes (TCs), a novel type of
      interstitial cell very recently discovered in myocardim (see
      http://www.telocytes.com). Electron microscopy, immunocytochemistry and analysis
      of several proangiogenic microRNAs provided evidence for TC involvement in neo
      angiogenesis after myocardial infarction. Electron microscopy showed the close
      spatial association of TCs with neoangiogenetic elements. Higher resolution
      images provided the following information: (a) the intercellular space between
      the abluminal face of endothelium and its surrounding TCs is frequently less than
      50 nm; (b) TCs establish multiple direct nanocontacts with endothelial cells,
      where the extracellular space seems obliterated; such nanocontacts have a length
      of 0.4-1.5 MUm; (c) the absence of basal membrane on the abluminal face of
      endothelial cell. Besides the physical contacts (either nanoscopic or
      microscopic) TCs presumably contribute to neo-angiognesis via paracrine secretion
      (as shown by immunocytochemistry for VEGF or NOS2). Last but not least, TCs
      contain measurable quantities of angiogenic microRNAs (e.g. let-7e, 10a, 21, 27b,
      100, 126-3p, 130a, 143, 155, 503). Taken together, the direct (physical) contact
      of TCs with endothelial tubes, as well as the indirect (chemical) positive
      influence within the 'angiogenic zones', suggests an important participation of
      TCs in neo-angiogenesis during the late stage of myocardial infarction.

PMID- 21895966
TI  - Regulatory T cell: a protection for tumour cells.
AB  - Characterized by immunosuppression regulatory T cells (Tregs) play a key role in
      maintaining immune tolerance. A growing number of tumours have been found with
      Tregs accumulating in microenvironment and patients with high density of Tregs in
      tumour stroma get a worse prognosis, which suggests that Tregs may inhibit anti
      tumour immunity in stroma, resulting in a poor prognosis. In this paper, we
      demonstrate the accumulation of Tregs in tumour stroma and the possible
      suppressive mechanisms. We also state the immunotherapy that has being used in
      animal and clinical trials.

PMID- 21895961
TI  - Ablation of ghrelin receptor reduces adiposity and improves insulin sensitivity
      during aging by regulating fat metabolism in white and brown adipose tissues.
AB  - Aging is associated with increased adiposity in white adipose tissues and
      impaired thermogenesis in brown adipose tissues; both contribute to increased
      incidences of obesity and type 2 diabetes. Ghrelin is the only known circulating
      orexigenic hormone that promotes adiposity. In this study, we show that ablation
      of the ghrelin receptor (growth hormone secretagogue receptor, GHS-R) improves
      insulin sensitivity during aging. Compared to wild-type (WT) mice, old Ghsr(-/-) 
      mice have reduced fat and preserve a healthier lipid profile. Old Ghsr(-/-)  mice
      also exhibit elevated energy expenditure and resting metabolic rate, yet have
      similar food intake and locomotor activity. While GHS-R expression in white and
      brown adipose tissues was below the detectable level in the young mice, GHS-R
      expression was readily detectable in visceral white fat and interscapular brown
      fat of the old mice. Gene expression profiles reveal that Ghsr ablation reduced
      glucose/lipid uptake and lipogenesis in white adipose tissues but increased
      thermogenic capacity in brown adipose tissues. Ghsr ablation prevents age
      associated decline in thermogenic gene expression of uncoupling protein 1 (UCP1).
      Cell culture studies in brown adipocytes further demonstrate that ghrelin
      suppresses the expression of adipogenic and thermogenic genes, while GHS-R
      antagonist abolishes ghrelin's effects and increases UCP1 expression. Hence, GHS
      R plays an important role in thermogenic impairment during aging. Ghsr ablation
      improves aging-associated obesity and insulin resistance by reducing adiposity
      and increasing thermogenesis. Growth hormone secretagogue receptor antagonists
      may be a new means of combating obesity by shifting the energy balance from
      obesogenesis to thermogenesis.

PMID- 21895970
TI  - Comparison of soymilk, powdered milk, Hank's balanced salt solution and tap water
      on periodontal ligament cell survival.
AB  - The purpose of this study was to evaluate the ability of soymilk, powdered milk,
      and Hank's balanced salt solution (HBSS) to maintain human periodontal ligament
      (PDL) cell viability in vitro. PDL cells were obtained from extracted healthy
      third molars and cultured in Dulbecco's modified Eagles medium (DMEM). The
      cultures were exposed for 1, 2, 4, and 8 h to experimental solutions (tap water
      served as negative control and DMEM as positive control) at 37 degrees C. The
      viable cells were then counted using the trypan blue exclusion technique. Data
      were analyzed by using one-way anova, post hoc Scheffe and two-way anova test.
      Statistical analysis showed that HBSS, powdered baby formula, and soymilk
      maintain cell viability equally well in different periods of times. Tap water
      cannot keep cells viable as well as other solutions. Soymilk and powdered baby
      formula can be recommended as suitable storage media for avulsed teeth for up to
      8 h.

PMID- 21895971
TI  - Biomimetic approach to extensive fracture of anterior teeth--a case report.
AB  - The fracture of anterior teeth in children and adolescents is a common injury.
      When most tooth structure is compromised and the broken fragment is not
      recovered, its restoration can become rather complex to both dentist and dental
      technician. Restoration of single anterior elements is one of the most demanding
      challenges in fixed prosthodontics. This article describes a clinical case of a
      13-year-old patient with an extensive fractured central incisor and contra
      lateral incisor. Endodontic treatment was performed on both teeth, and a
      temporary removable appliance was made for esthetics. One month later, an
      indirect esthetic post and core was made for each tooth, and provisionals were
      placed. After a 6-month period of soft tissue stabilization, two pressed all
      ceramic crowns were fabricated and bonded to the preparations. The authors
      believe this to be a stable long-term option relative to the reminiscent tooth
      structure, esthetic demand, and occlusal features of the case.

PMID- 21895972
TI  - Education on and prevention of dental trauma: it's time to act!
AB  - Dental trauma is, unfortunately, not uncommon and may be even more prevalent in
      high-risk populations. It should be emphasized and acknowledged that many cases
      of dental trauma are preventable. Appropriate management includes primary
      prevention, i.e. avoidance of pathology development, and secondary prevention,
      i.e. early diagnosing and treatment of the pathology before significant morbidity
      occurs. The aim of this article is to provide a review of the current dental
      trauma literature with regard to education and knowledge and with relevance to
      primary and secondary prevention. As the duty of providing the public with
      measures for the maintenance of proper oral health is of the dental profession,
      the responsibility of providing primary and secondary prevention of dental trauma
      is of dentists, dental hygienists, and dental nurses. They may, and should,
      educate other medical, paramedical, and non-medical professionals, taking into
      account that those non-dental professionals could not maintain a high level of
      knowledge and service regarding dental trauma without a continuous backing by the
      dental professionals. It should be remembered that as the prevalence of dental
      decay has reduced in the Western world during recent decades, dental trauma plays
      a significant part in causing dental morbidity and mortality (tooth loss). It
      seems that now is the time to act for the benefit of our community and move from
      'treating' toward 'managing' risk factors and prevention.

PMID- 21895979
TI  - Bupropion as an augmenting agent in patients of depression with partial response.
AB  - The objective of this study is to evaluate the effects of bupropion as an add-on
      therapy to selective serotonin reuptake inhibitor (SSRI) on patients of major
      depressive disorder with partial response. This prospective, randomized,
      controlled and single-blind study was conducted in sixty patients suffering from
      major depressive disorder as per Diagnostic and Statistical Manual (DSM)-IV TR
      criteria, who were having Hamilton depression rating scale (HDRS) score >=16
      after 4 weeks of treatment with SSRIs. Group A received SSRI plus placebo and
      group B received SSRI plus bupropion. Evaluation was performed based on changes
      in HDRS score, Montgomery and Asberg depression rating scale (MADRS), Amritsar
      depressive inventory (ADI) and spontaneously reported adverse effects. There was
      a significant decrease in the HDRS, MADRS and ADI scores as compared to baseline
      in both groups. However, the mean decrease in depression score was more in group
      B than in group A. The percentage decrease of remitters was also significantly
      more in group B (60% as per HDRS score and 63% as per MADRS score), as compared
      to group A (24% as per HDRS score and 27% as per MADRS score) (p < 0.05), at the
      end of treatment. In conclusion, bupropion add-on can act as augmenting agent in
      patients of depression with partial response to SSRIs.

PMID- 21895976
TI  - Reverse tissue expansion by liposuction deflation for revision of post-surgical
      thigh scars.
AB  - Scars hypertrophy and widen when stretching mechanical forces are applied to
      resilient newly formed collagen before it reaches final maturity marring the
      final result of many surgical procedures and resulting in a clinical problem for
      many patients. Scar revision by surgical excision remains the traditional
      treatment for hypertrophic or widespread scars. It relies upon recruitment of
      local tissues for closure of the ensuing defect. Providing tension-free skin
      closure is the best option to avoid recurrence. Although tissue expansion
      procedure is a valuable and reliable technique for scar revision, it has its own
      disadvantages and potential complications. We describe an alternative method for
      scar revision that may be applicable in certain situations. Instead of expanding
      the soft tissues to make available additional skin, deflation by liposuction may
      be affected to relax the skin envelope thus indirectly providing additional skin
      for scar revision. We call this method 'reverse tissue expansion'.

PMID- 21895978
TI  - Inhibitory effects of continuous ingestion of Schisandrin A on CYP3A in the rat.
AB  - The objective of this study was to evaluate the ability of schisandrin A (SchA)
      to inhibit the P450 enzyme CYP3A in vivo. Male Sprague-Dawley rats were
      intragastrically administered with varied doses of SchA (8 mg/kg or 16 mg/kg or
      32 mg/kg) or 75 mg/kg ketoconazole for three consecutive days. Ketoconazole, a
      chemical inhibitor of CYP3A, was used as positive control. Subsequently, changes
      in hepatic microsome CYP3A activity and the pharmacokinetic profiles of midazolam
      (MDZ), a specific CYP3A substrate, were studied as indicators of rat hepatic
      microsomal activity of CYP3A. Differences in the plasma concentrations of MDZ and
      its related metabolites and the hepatic microsome concentrations of 1'
      hydroxymidazolam were analysed by high-performance liquid chromatography. The
      current results provide direct and explicit evidence that SchA produced
      concentration-dependent inhibition of MDZ metabolite formation in rat liver
      microsomes (p < 0.01 or p < 0.001). Regular SchA consumption also caused
      concentration-dependent increase in Cmax and area under the concentration-time
      curve (AUC0-t and AUC0-infinity ) of peroral MDZ (p < 0.05 or p < 0.01) compared
      to vehicle-treated rats, whereas those of its metabolites (1'-hydroxymidazolam)
      were reduced (p < 0.05 or p < 0.01). Analysis of the data suggests that changes
      in the pharmacokinetic profiles of peroral MDZ in the rat model were contributed
      mainly to SchA inhibition of CYP3A activity. These results suggest that SchA, as
      an inhibitor of CYP3A, possesses a clinically beneficial property of altering the
      disposition of drugs metabolized by CYP3A. 

PMID- 21895974
TI  - Silencing synaptic communication between random interneurons during Drosophila
      larval locomotion.
AB  - Genetic manipulation of individual neurons provides a powerful approach toward
      understanding their contribution to stereotypic behaviors. We describe and
      evaluate a method for identifying candidate interneurons and associated neuropile
      compartments that mediate Drosophila larval locomotion. We created Drosophila
      larvae that express green fluorescent protein (GFP) and a shibire(ts1) (shi(ts1))
      transgene (a temperature-sensitive neuronal silencer) in small numbers of
      randomly selected cholinergic neurons. These larvae were screened for aberrant
      behavior at an elevated temperature (31-32 degrees C). Among larvae with abnormal
      locomotion or sensory-motor responses, some had very small numbers of GFP-labeled
      temperature-sensitive interneurons. Labeled ascending interneurons projecting
      from the abdominal ganglia to specific brain neuropile compartments emerged as
      candidates for mediation of larval locomotion. Random targeting of small sets of
      neurons for functional evaluation, together with anatomical mapping of their
      processes, provides a tool for identifying the regions of the central nervous
      system that are required for normal locomotion. We discuss the limitations and
      advantages of this approach to discovery of interneurons that regulate motor
      behavior.

PMID- 21895977
TI  - Kv 7 positive modulators reduce detrusor overactivity and increase bladder
      capacity in rats.
AB  - The effects of the Kv 7 channel modulators retigabine (opener) and XE991
      (blocker) on rat bladder function were investigated ex vivo and in vivo to assess
      the potential of Kv 7 openers for the treatment of overactive bladder. In organ
      bath studies, capsaicin-stimulated rat urinary bladder rings were exposed to
      retigabine and XE991 and the effect on tension and amplitude was evaluated. In
      anaesthetized rats, retigabine (0.01-1 mg/kg, i.v.) effects on bladder function,
      in which overactivity was induced by continuous infusion of 0.5% acetic acid,
      were assessed. The effect of retigabine (10 mg/kg, p.o.) on cystometric
      parameters was also measured in conscious rats with capsaicin-induced irritated
      bladders. Localization of Kv 7 subunits within bladder tissue was analysed by RT
      qPCR and western blotting. In organ bath studies, retigabine robustly reduced
      capsaicin-induced contractility of bladder rings and this effect was blocked by
      XE991 confirming the specificity of action via Kv 7 channels. In anaesthetized
      rats with acetic acid-irritated bladders, retigabine markedly increased bladder
      capacity with no concomitant reduction in blood pressure. Retigabine also reduced
      bladder pressure and delayed voiding in conscious rats with capsaicin-irritated
      bladders. Kv 7.1, Kv 7.4 and Kv 7.5 subunit mRNA transcripts were detected in rat
      bladder. Western blot analysis confirmed that Kv 7.4 subunit protein was
      expressed in rat bladder. These results suggest that retigabine and other Kv 7
      channel positive modulators may have beneficial effects on bladder overactivity
      partly via activation of Kv 7 channels expressed in bladder tissue. 

PMID- 21895984
TI  - Representation of multi-target activity landscapes through target pair-based
      compound encoding in self-organizing maps.
AB  - Activity landscape representations provide access to structure-activity
      relationships information in compound data sets. In general, activity landscape
      models integrate molecular similarity relationships with biological activity
      data. Typically, activity against a single target is monitored. However, for
      steadily increasing numbers of compounds, activity against multiple targets is
      reported, resulting in an opportunity, and often a need, to explore multi-target
      structure-activity relationships. It would be attractive to utilize activity
      landscape representations to aid in this process, but the design of activity
      landscapes for multiple targets is a complicated task. Only recently has a first
      multi-target landscape model been introduced, consisting of an annotated compound
      network focused on the systematic detection of activity cliffs. Herein, we report
      a conceptually different multi-target activity landscape design that is based on
      a 2D projection of chemical reference space using self-organizing maps and
      encodes compounds as arrays of pair-wise target activity relationships. In this
      context, we introduce the concept of discontinuity in multi-target activity
      space. The well-ordered activity landscape model highlights centers of
      discontinuity in activity space and is straightforward to interpret. It has been
      applied to analyze compound data sets with three, four, and five target
      annotations and identify multi-target structure-activity relationships
      determinants in analog series.

PMID- 21895982
TI  - Synthesis and biological evaluation of some novel 1,4-dihydropyridines as
      potential antitubercular agents.
AB  - Recent studies showed that 1,4-dihydropyridine-3,5-dicarbamoyl derivatives with
      lipophilic groups have significant antitubercular activity. In this study, we
      have synthesized new derivatives of 1,4-dihydropyridines bearing carbmethoxy and
      carbethoxy group at C-3 and C-5 of the 1,4-dihydropyridine ring. In addition, 1H
      pyrazole ring is substituted at C-4 position. These analogues were synthesized by
      multi-component Hantzsch reaction. The in vitro antitubercular activity of
      compounds against Mycobacterium tuberculosis H(37) Rv was evaluated. The lowest
      minimum inhibitory concentration value, 0.02 MUg/mL and SI > 500, was found for
      dimethyl 1,4-dihydro-4-(3-(4-nitrophenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6
      dimethylpyridine-3,5-dicarboxylate 3f, diethyl 1,4-dihydro-4-(3-(4-fluorophenyl)
      1-phenyl-1H-pyrazol-4-yl)-2,6-dimethylpyridine-3,5-dicarboxylate 4c and diethyl
      1,4-dihydro-4-(3-(4-bromophenyl)-1-phenyl-1H-pyrazol-4-yl)-2,6-dimethyl pyridine
      3,5-dicarboxylate 4e, making them more potent than first-line antitubercular drug
      isoniazid. In addition, these compounds exhibited relatively low cytotoxicity.

PMID- 21895981
TI  - Mannose-binding lectin (MBL2) polymorphisms and inflammation in hypertensive
      patients.
AB  - We investigated the possible role of Mannose binding lectin 2 (MBL2) functional
      polymorphisms in the prevalence of hypertension and hypertensive end-organ damage
      in 300 hypertensive patients and 313 normotensive individuals from Southern
      Brazil. Hypertensive subjects with MBL2 AO/OO genotypes presented lower C
      reactive protein levels than AA individuals and consequently lower inflammatory
      status.

PMID- 21895986
TI  - 2D- and 3D-quantitative structure-activity relationship studies for a series of
      phenazine N,N'-dioxide as antitumour agents.
AB  - Hypoxic regions of tumours are associated with increased resistance to radiation
      and chemotherapy. Nevertheless, hypoxia has been used as a tool for specific
      activation of some antitumour prodrugs, named bioreductive agents. Phenazine
      dioxides are an example of such bioreductive prodrugs. Our 2D-quantitative
      structure activity relationship studies established that phenazine dioxides
      electronic and lipophilic descriptors are related to survival fraction in oxia or
      in hypoxia. Additionally, statistically significant models, derived by partial
      least squares, were obtained between survival fraction in oxia and comparative
      molecular field analysis standard model (r2 = 0.755, q2 = 0.505 and F = 26.70) or
      comparative molecular similarity indices analysis-combined steric and
      electrostatic fields (r2 = 0.757, q2 = 0.527 and F = 14.93), and survival
      fraction in hypoxia and comparative molecular field analysis standard model (r2 =
      0.736, q2 = 0.521 and F = 18.63) or comparative molecular similarity indices
      analysis-hydrogen bond acceptor field (r2 = 0.858, q2 = 0.737 and F = 27.19).
      Categorical classification was used for the biological parameter selective
      cytotoxicity emerging also good models, derived by soft independent modelling of
      class analogy, with both comparative molecular field analysis standard model (96%
      of overall classification accuracy) and comparative molecular similarity indices
      analysis-steric field (92% of overall classification accuracy). 2D- and 3D
      quantitative structure-activity relationships models provided important insights
      into the chemical and structural basis involved in the molecular recognition
      process of these phenazines as bioreductive agents and should be useful for the
      design of new structurally related analogues with improved potency.

PMID- 21895985
TI  - QSAR models for phosphoramidate prodrugs of 2'-methylcytidine as inhibitors of
      hepatitis C virus based on PSO boosting.
AB  - In the current study, boosting regression has been proposed to model the
      activities of a series of phosphoramidate prodrugs of 2'-methylcytidine as
      inhibitors of hepatitis C virus. The stepwise multiple linear regression and
      particle swarm optimization strategies are used to select descriptors which are
      responsible for the inhibitory activity of these compounds. As comparisons to the
      boosting regression method, the multiple linear regression, back-propagation
      neural networks, and support vector machine have also been investigated.
      Experimental results have shown that the boosting can drastically enhance the
      generalization performance of individual multiple linear regression model and the
      particle swarm optimization-boosting method is a well-performing technique in
      quantitative structure-activity relationship studies superior to support vector
      machine. The squared correlation coefficient and standard deviation of the best
      model are 0.744 and 0.438 for the training set and 0.710 and 0.748 for the test
      set.

PMID- 21895983
TI  - Design, synthesis, and in vitro antitumor activity evaluation of novel 4
      pyrrylamino quinazoline derivatives.
AB  - Here, we describe the design and synthesis of two series of 4-pyrrylamino
      quinazolines as new analogs of the epidermal growth factor receptor inhibitor
      gefitinib. In vitro antitumor activity of these novel compounds against
      pancreatic (Miapaca2) and prostate (DU145) cancer cell lines was evaluated.
      Compared with the parental gefitinib, all 18 derivatives show a greatly increased
      cytotoxicity to cancer cells. In vitro kinase inhibitory activity on epidermal
      growth factor receptor was also investigated. Among them, compounds GI-6, GII-4,
      GII-6, GII-8, and GII-9 are more potential receptor tyrosine kinase (RTK)
      inhibitors. Based on these results, we propose simple structure-activity
      relationship to provide information for designing and developing more potent
      antitumor agents.

PMID- 21895973
TI  - Microbiologic endodontic status of young traumatized tooth.
AB  - Traumatic dental injuries could expose the dentin and, even the pulp, to the oral
      environment, making possible their contamination. The presence of microorganisms
      causes pulpal disease and further a tecidual clutter in the periradicular region.
      The therapy of periradicular pathosis is the consequence of a correct diagnoses
      which depends on the knowledge of the nature and complexity of endodontic
      infections. As there is no information on the microbiology of primary endodontic
      infection in young teeth, the aim of the current study was to investigate the
      microbiologic status of root canals from permanent young teeth with primary
      endodontic infection. Twelve patients with the need for endodontic treatment
      participated in the study. The selected teeth were uniradicular and had an
      incomplete root formation. They had untreated necrotic pulp. After the access
      preparation, nineteen microbiologic samples were obtained from the root canals
      with sterile paper points. Afterwards, the paper points were pooled in a sterile
      tube containing 2 ml of prereduced transport fluid. The samples were diluted and
      spread onto plates with selective medium for Enterococcus spp. and for yeast
      species and onto plates with non-selective medium. A quantitative analysis was
      performed. The mean number of cultivable bacterial cells in the root canals was
      5.7 * 10(6). In four samples (21.05%) black pigmented species were recovered and
      the mean number of cells was 6.5 * 10(5). One specimen (5.25%) showed the growth
      of Enterococcus species and the mean number of cells in this case was of 1.5 *
      10(4) . The results showed a root canal microbiota with similar design as seen in
      completely formed teeth.

PMID- 21895975
TI  - Crystal structure of Onconase at 1.1 A resolution--insights into substrate
      binding and collective motion.
AB  - Onconase((r)) (ONC) is an amphibian member of the pancreatic ribonuclease
      superfamily that is selectively toxic to tumor cells. It is a much less efficient
      enzyme than the archetypal ribonuclease A and, in an attempt to gain further
      insight, we report the first atomic resolution crystal structure of ONC,
      determined in complex with sulfate ions at 100 K. The electron density map is of
      a quality sufficient to reveal significant nonplanarity in several peptide bonds.
      The majority of active site residues are very well defined, with the exceptions
      being Lys31 from the catalytic triad and Lys33 from the B(1) subsite, which are
      relatively mobile but rigidify upon nucleotide binding. Cryocooling causes a
      compaction of the unit cell and the protein contained within. This is principally
      the result of an inward movement of one of the lobes of the enzyme (lobe 2),
      which also narrows the active site cleft. Binding a nucleotide in place of
      sulfate is associated with an approximately perpendicular movement of lobe 2 and
      has little further effect on the cleft width. Aspects of this deformation are
      present in the principal axes of anisotropy extracted from C(alpha) atomic
      displacement parameters, indicating its intrinsic nature. The three lowest
      frequency modes of ONC motion predicted by an anisotropic network model are
      compaction/expansion variations in which lobe 2 is the prime mover. Two of these
      have high similarity to the cryocooling response and imply that the essential
      'breathing' motion of ribonuclease A is conserved in ONC. Instead, shifts in
      conformational equilibria may contribute to the reduced ribonucleolytic activity
      of ONC.

PMID- 21895980
TI  - Genetic, clinical and behavioural determinants of vitamin K-antagonist dose-
      explored through multivariable modelling and visualization.
AB  - Vitamin K antagonists (VKA) are highly effective anticoagulants but their use is
      hampered by multiple interactions with food and medicine and a narrow therapeutic
      range. The large variation in dose requirements has led to the development of
      several dosing algorithms based on pharmacogenetic and clinical variables. In
      contrast, evidence about the influence of behavioural (i.e. diet and exercise)
      and socio-psychological factors is sparse. To investigate the impact of
      pharmacogenetic, clinical, behavioural and socio-psychological factors on
      maintenance dose of VKA. In a cross-sectional study, we interviewed 250
      consecutive patients from an anticoagulant clinic and subsequently measured
      pharmacogenetic and anthropometric variables. Statistical analyses were carried
      out using linear regression and multivariable models with visualization features.
      In both types of analyses, the strongest determinants of VKA dose were
      polymorphisms in the VKORC1 and CYP2C9 genes and age. Half of the variation in
      VKA dose could be explained by a linear regression model including four
      variables, while a multivariable model with 20 pharmacogenetic and clinical
      variables explained 60%. A multivariable model including 94 predictor variables
      was not notably better regarding predictive performance, but visualization of
      this model offered information about the correlation structure between predictor
      variables. The strongest determinants of VKA dose are well-known pharmacogenetic
      variables and age. The variables describing health-related behaviour and socio
      psychological factors are strongly inter-correlated and not useful in dosing
      algorithms. 

PMID- 21895987
TI  - Hemoglobin Lepore Hollandia in India.
AB  - INTRODUCTION: Hb Lepore is a structurally abnormal hemoglobin in which the
      abnormal globin chain is a hybrid or fused deltabeta globin chain. In the
      heterozygous condition, Hb Lepore produces the phenotype of heterozygous beta
      thalassemia with slightly raised HbF levels. METHOD: Using a combination of HPLC
      and DNA analysis, we have identified eight individuals with Hb Lepore Hollandia
      from three families including seven heterozygotes and one compound heterozygote
      with beta thalassemia who presented with a severe clinical phenotype. RESULTS:
      All the heterozygotes showed elevated levels of HbF with a mean of 3.2%. Hb
      Lepore Hollandia genes were associated with a single beta globin cluster
      haplotype [- - - - - - +] indicating a common origin. CONCLUSION: Hemoglobin
      Lepore Hollandia is a relatively uncommon variant in the Indian population and
      can be identified using a combination of chromatographic, electrophoretic, and
      molecular analysis.

PMID- 21895989
TI  - State of the art in natural killer cell malignancies.
AB  - The recently updated World Health Organization (WHO) classification of tumors of
      hematopoietic and lymphoid tissues, published in 2008, has made great advances in
      revising the disorders previously included in the pool of natural killer (NK)
      cell tumors. Although NK cell neoplasms represent a relatively rare group of
      diseases, accounting for <5% of all lymphoid neoplasms, they include very
      distinctive conditions both clinically and pathologically. This family of
      diseases includes the most indolent clinical forms, such as the provisional new
      entry of chronic lymphoproliferative disorder of NK cells (CLPD-NK) in the WHO
      classification, as well as one of the most fatal diseases recognized in medical
      oncology, aggressive NK cell leukemia (ANKL), which is characterized by a
      prognosis of weeks, or even days. In addition, some disorders previously
      identified as blastic NK cell lymphoma within the NK cell system have been more
      properly defined and included in the blastic plasmacytoid dentritic cell
      neoplasms, although rare cases of bona fide immature NK lymphoid tumors (now
      classified as NK cell lymphoblastic leukemia/lymphoma) have been reported in the
      literature. This paper focuses on recent concepts and progress in morphology,
      pathogenesis, clinicopathological features, treatment approaches, and outcomes of
      NK cell malignancies.

PMID- 21895988
TI  - Counting of leukocytes in samples from G-CSF mobilized donors, leukapheresis
      products, and cord blood: the performances of an analyzer with dedicated
      profiles.
AB  - INTRODUCTION: Accurate white blood cell counting (WBC) and differential count by
      blood analyzers could allow a more informative characterization of granulocyte
      colony-stimulating factor (G-CSF) mobilized blood (MB), leukapheresis products
      (LP), and cord blood (CB). However, reliable counting by a blood cell analyzer in
      this setting is a major challenge owing to quali-quantitative abnormalities of
      blood cells. METHODS: We evaluated the performances of the analyzer Pentra DX 120
      by Horiba ABX working with dedicated cell-gating profiles, which generate three
      part differential counts in samples obtained from donors' MB, LP, and CB. The
      results of the analyzer were compared to counts obtained by flow cytometry and
      manual counts, the latter performed for reference validation and in the case of
      discrepant results between study and reference counts. RESULTS: Pentra DX 120
      generated highly correlated counts (R > 0.91 in all cases) to those obtained by
      flow cytometry in all samples (MB, LP, and CB) with high degree of count accuracy
      in most cases and referred to WBC absolute count and differential count including
      lymphocytes (LYM) %, monocytes (MON) %, and polymorphonuclear leukocytes (PMN) %.
      Accuracy, judged by the difference between study and reference counts and
      expressed as percentage of reference count, ranged from 0.8% to 8.6%, and
      sporadic loss of accuracy occurred for MON % only in no more than 10% of CB
      samples. CONCLUSION: The ABX Pentra DX 120 provided accurate WBC count and
      differential count during MB, LP, and CB analyses and allowed a better
      characterization of donors' hematologic status and graft composition.

PMID- 21895990
TI  - Adolescent attention deficit hyperactivity disorder and susceptibility to
      psychosis in adulthood: a review of the literature and a phenomenological case
      report.
AB  - AIM: In contrast to affective disorders, some forms of personality disorders and
      drug addiction, schizophrenia is commonly not considered to be a sequela of
      attention deficit hyperactivity disorder. However, attention deficit
      hyperactivity disorder and the prodromal stages of schizophrenia spectrum
      disorders do exhibit a number of common central features. To facilitate the early
      treatment of schizophrenic symptoms, the detection of discrete and subtle
      alterations in the prodromal stages of incipient psychoses is particularly
      important. METHODS: We review the literature on the prodromal symptoms of
      psychosis and present a case report, in which a phenomenological approach was
      used to identify subtle alterations linked to anomalous self-experience. RESULTS:
      Using the Examination of Anomalous Self-Experience symptom checklist, the case
      report presented here reveals attention deficit hyperactivity disorder symptoms
      in adolescence as a precursor state of psychosis in adulthood. CONCLUSIONS: The
      characteristics of this schizophrenia spectrum disorder case and its time course
      are derived from the specific distribution pattern of Examination of Anomalous
      Self-Experience items. When treating adolescent attention deficit hyperactivity
      disorder patients, the rare possibility of the development of schizophrenia
      spectrum disorder from attention deficit hyperactivity disorder like symptoms
      should be kept in mind.

PMID- 21895991
TI  - New developments and concepts related to biomarker application to vaccines.
AB  - This minireview will provide a perspective on new developments and concepts
      related to biomarker applications for vaccines. In the context of preventive
      vaccines, biomarkers have the potential to predict adverse events in select
      subjects due to differences in genetic make-up/underlying medical conditions or
      to predict effectiveness (good versus poor response). When expanding them to
      therapeutic vaccines, their utility in identification of patients most likely to
      respond favourably (or avoid potentially negative effects of treatment) becomes
      self-explanatory. Despite the progress made so far on dissection of various
      pathways of biological significance in humans, there is still plenty to unravel
      about the mysteries related to the quantitative and qualitative aspects of the
      human host response. This review will provide a focused overview of new concepts
      and developments in the field of vaccine biomarkers including (i) vaccine
      dependent signatures predicting subject response and safety, (ii) predicting
      therapeutic vaccine efficacy in chronic diseases, (iii) exploring the genetic
      make-up of the host that may modulate subject-specific adverse events or affect
      the quality of immune responses, and (iv) the topic of volunteer stratification
      as a result of biomarker screening (e.g. for therapeutic vaccines but also
      potentially for preventive vaccines) or as a reflection of an effort to compare
      select groups (e.g. vaccinated subjects versus patients recovering from
      infection) to enable the discovery of clinically relevant biomarkers for
      preventive vaccines.

PMID- 21895993
TI  - Enzymes for the laundry industries: tapping the vast metagenomic pool of alkaline
      proteases.
AB  - In the wide field of laundry and cleaning applications, there is an unbroken need
      for novel detergent proteases excelling in high stability and activity and a
      suitable substrate range. We demonstrated the large amount of highly diverse
      subtilase sequences present in metagenomic DNA by recovering 57 non-redundant
      subtilase sequence tags with degenerate primers. Furthermore, an activity- as
      well as a sequence homology-based screening of metagenomic DNA libraries was
      carried out, using alkaline soil and habitat enrichments as a source of DNA. In
      this way, 18 diverse full-length protease genes were recovered, sharing only 37
      85% of their amino acid residues with already known protease genes. Active clones
      were biochemically characterized and subjected to a laundry application assay,
      leading to the identification of three promising detergent proteases. According
      to sequence similarity, two proteases (HP53 and HP70) can be classified as
      subtilases, while the third enzyme (HP23) belongs to chymotrypsin-like S1 serine
      proteases, a class of enzymes that has not yet been described for the use in
      laundry and cleaning applications.

PMID- 21895994
TI  - A novel antimicrobial protein for plant protection consisting of a Xanthomonas
      oryzae harpin and active domains of cecropin A and melittin.
AB  - Discoveries about antimicrobial peptides and plant defence activators have made
      possible the de novo and rational design of novel peptides for use in crop
      protection. Here we report a novel chimeric protein, Hcm1, which was made by
      linking the active domains of cecropin A and melittin to the hypersensitive
      response (HR)-elicitor Hpa1 of Xanthomonas oryzae pv. oryzicola, the causal agent
      of rice bacterial leaf streak. The resulting chimeric protein maintained not only
      the HR-inducing property of the harpin, but also the antimicrobial activity of
      the cecropin A-melittin hybrid. Hcm1 was purified from engineered Escherichia
      coli and evaluated in terms of the minimal inhibitory concentration (MIC) and the
      50% effective dose (ED(50)) against important plant pathogenic bacteria and
      fungi. Importantly, the protein acted as a potential pesticide by inducing
      disease resistance for viral, bacterial and fungal pathogens. This designed drug
      can be considered as a lead compound for use in plant protection, either for the
      development of new broad-spectrum pesticides or for expression in transgenic
      plants.

PMID- 21895992
TI  - J-LEAPS peptide and LEAPS dendritic cell vaccines.
AB  - The J-LEAPS vaccines contain a peptide from beta-2-microglobulin covalently
      attached to disease-related peptides of 8-30 amino acids which contain a T cell
      epitope. The J-LEAPS vaccines can initiate a protective Th1 immune response or
      modulate an ongoing Th17 autoimmune response to the peptide. J-LEAPS vaccines
      activate and direct the nature of the subsequent immune response by promoting the
      maturation of precursor cells into a unique type of dendritic cell that produces
      interleukin 12, but not IL-1 or tumour necrosis factor, and presents the
      antigenic peptide to T cells. Adoptive transfer of JgD-LEAPS dendritic cells,
      matured with an anti-HSV-1 vaccine, promoted antigen-specific Th1 protection
      against lethal challenge with the virus. J-LEAPS peptide immunogens and J-LEAPS
      dendritic cell vaccines have potential applications for antimicrobial prevention
      and therapy, treatment of autoimmune diseases, and for cancer immunotherapy.

PMID- 21895996
TI  - Selective removal of transition metals from acidic mine waters by novel consortia
      of acidophilic sulfidogenic bacteria.
AB  - Two continuous-flow bench-scale bioreactor systems populated by mixed communities
      of acidophilic sulfate-reducing bacteria were constructed and tested for their
      abilities to promote the selective precipitation of transition metals (as
      sulfides) present in synthetic mine waters, using glycerol as electron donor. The
      objective with the first system (selective precipitation of copper from acidic
      mine water containing a variety of soluble metals) was achieved by maintaining a
      bioreactor pH of ~ 2.2-2.5. The second system was fed with acidic (pH 2.5)
      synthetic mine water containing 3 mM of both zinc and ferrous iron, and varying
      concentrations (0.5-30 mM) of aluminium. Selective precipitation of zinc sulfide
      was possible by operating the bioreactor at pH 4.0 and supplementing the
      synthetic mine water with 4 mM glycerol. Analysis of the microbial populations in
      the bioreactors showed that they changed with varying operational parameters, and
      novel acidophilic bacteria (including one sulfidogen) were isolated from the
      bioreactors. The acidophilic sulfidogenic bioreactors provided 'proof of
      principle' that segregation of metals present in mine waters is possible using
      simple online systems within which controlled pH conditions are maintained. The
      modular units are versatile and robust, and involve minimum engineering
      complexity.

PMID- 21895995
TI  - Hydrogen production by recombinant Escherichia coli strains.
AB  - The production of hydrogen via microbial biotechnology is an active field of
      research. Given its ease of manipulation, the best-studied bacterium Escherichia
      coli has become a workhorse for enhanced hydrogen production through metabolic
      engineering, heterologous gene expression, adaptive evolution, and protein
      engineering. Herein, the utility of E. coli strains to produce hydrogen, via
      native hydrogenases or heterologous ones, is reviewed. In addition, potential
      strategies for increasing hydrogen production are outlined and whole-cell systems
      and cell-free systems are compared.

PMID- 21895997
TI  - The glycerophospholipid inventory of Pseudomonas putida is conserved between
      strains and enables growth condition-related alterations.
AB  - Microorganisms, such as Pseudomonas putida, utilize specific physical properties
      of cellular membrane constituents, mainly glycerophospholipids, to (re-)adjust
      the membrane barrier to environmental stresses. Building a basis for membrane
      composition/function studies, we inventoried the glycerophospholipids of
      different Pseudomonas and challenged membranes of growing cells with n-butanol.
      Using a new high-resolution liquid chromatography/mass spectrometry (LC/MS)
      method, 127 glycerophospholipid species [e.g. phosphatidylethanolamine PE(32:1)]
      with up to five fatty acid combinations were detected. The glycerophospholipid
      inventory consists of 305 distinct glycerophospholipids [e.g. PE(16:0/16:1)],
      thereof 14 lyso-glycerophospholipids, revealing conserved compositions within the
      four investigated pseudomonads P. putida KT2440, DOT-T1E, S12 and Pseudomonas sp.
      strain VLB120. Furthermore, we addressed the influence of environmental
      conditions on the glycerophospholipid composition of Pseudomonas via long-time
      exposure to the sublethal n-butanol concentration of 1% (v/v), focusing on: (i)
      relative amounts of glycerophospholipid species, (ii) glycerophospholipid head
      group composition, (iii) fatty acid chain length, (iv) degree of saturation and
      (v) cis/trans isomerization of unsaturated fatty acids. Observed alterations
      consist of changing head group compositions and for the solvent-sensitive strain
      KT2440 diminished fatty acid saturation degrees. Minor changes in the
      glycerophospholipid composition of the solvent-tolerant strains P. putida S12 and
      Pseudomonas sp. VLB120 suggest different strategies of the investigated
      Pseudomonas to maintain the barrier function of cellular membranes.

PMID- 21895998
TI  - Attenuated Salmonella enteritidis E23 as a vehicle for the rectal delivery of DNA
      vaccine coding for HIV-1 polyepitope CTL immunogen.
AB  - This study is focusing on elucidation of the capacity of attenuated Salmonella
      enteritidis E23 (cya, crp) to serve as a vehicle for the rectal delivery of the
      DNA vaccine. Earlier for creation HIV-1 candidate DNA vaccine we have designed
      the polyepitope protein TCI (T-cell immunogen), which comprises over 80 CTL
      epitopes from subtype A, B and C HIV-1 proteins. The gene coding for TCI protein
      was used to construct the eukaryotic expression plasmid pcDNA-TCI. The attenuated
      S. enteritidis E23 was transformed by electroporation with recombinant plasmid
      pcDNA-TCI and the expression of the TCI gene was determined in vitro and in vivo.
      BALB/c mice were rectally immunized with S. enteritidis E23/pcDNA-TCI (108 cfu)
      twice at 4 week interval. Bacteria were not pathogenic for mice and spontaneously
      eliminated from mice spleen and liver to 60 days post the immunization.
      Detectable antibodies were generated in 2 weeks after immunization and their
      level increased after second immunization. The results of INF-gamma ELISpot show
      that mice immunized with S. enteritidis E23/pcDNA-TCI elicited HIV-specific
      cellular immune response. This study demonstrates that attenuated S. enteritidis
      E23 is an effective live vector for rectal delivery of the DNA vaccine pcDNA-TCI
      to generate humoral and T-cellular responses against HIV-1.

PMID- 21895999
TI  - Effects of cationic hydroxyethyl cellulose on glucose metabolism and obesity in a
      diet-induced obesity mouse model.
AB  - BACKGROUND: To investigate the effect of a new soluble fiber, namely cationic
      hydroxyethyl cellulose (cHEC), on weight loss and metabolic disorders associated
      with obesity using a high-fat diet-induced obese mouse model. METHODS: Obese male
      C57BL/6J (B6) mice were fed high-fat (60% kcal) diets supplemented with cHEC for
      5 weeks. Body weight, energy intake, mesenteric adipose and liver weights, plasma
      cholesterol, plasma insulin, glucose, adiponectin, and leptin were assessed to
      determine the effects of cHEC. Hepatic and fecal lipids were also analyzed to
      investigate the effect of cHEC on lipid absorption and metabolism. RESULTS:
      Supplementation of the high-fat diet with cHEC resulted in significant weight
      loss in obese mice. In addition, significant decreases were seen in mesenteric
      adipose and liver weights, as well as concentrations of plasma cholesterol and
      hepatic lipids. A significant improvement in glucose homeostasis, insulin
      sensitivity, and leptin concentrations were observed at 4% cHEC. Moreover,
      increases in fecal excretion of total bile acids, sterols, and fats indicated
      altered fat absorption when cHEC was supplemented in the diet. CONCLUSIONS: We
      have shown in the present study that cHEC reduces body weight, improves insulin
      sensitivity, and prevents the development of metabolic syndrome. Furthermore, the
      effects of cHEC on glucose and lipid homeostasis in B6 mice are mediated by
      improvements in leptin sensitivity resulting from reduced fat absorption.

PMID- 21896000
TI  - Explaining risks and benefits.

PMID- 21896001
TI  - Motor preparation in unilateral cerebral palsy.

PMID- 21896002
TI  - Motor repertoire and neurological outcome in preterm infants.

PMID- 21896003
TI  - Grip force coordination during bimanual tasks in unilateral cerebral palsy.
AB  - AIM: The aim of the study was to investigate coordination of fingertip forces
      during an asymmetrical bimanual task in children with unilateral cerebral palsy
      (CP). METHOD: Twelve participants (six males, six females; mean age 14y 4mo, SD
      3.3y; range 9-20y;) with unilateral CP (eight right-sided, four left-sided) and
      15 age-matched typically developing participants (five males, 10 females; mean
      age 14y 3mo, SD 2.9y; range 9-18y,) were included. Participants were instructed
      to hold custom-made grip devices in each hand and place one device on top of the
      other. The grip force and load force were recorded simultaneously in both hands.
      RESULTS: Temporal coordination between the two hands was impaired in the
      participants with CP (compared with that in typically developing participants),
      that is they initiated the task by decreasing grip force in the releasing hand
      before increasing the force in the holding hand. The grip force increase in the
      holding hand was also smaller in participants with CP (involved hand/non-dominant
      hand releasing, p<0.001; non-involved hand/dominant hand releasing, p=0.007),
      indicating deficient scaling of force amplitude. The impairment was greater when
      participants with CP used their non-involved hand as the holding hand.
      INTERPRETATION: Temporal coordination and scaling of fingertip forces were
      impaired in both hands in participants with CP. The non-involved hand was
      strongly affected by activity in the involved hand, which may explain why
      children with unilateral CP prefer to use only one hand during tasks that are
      typically performed with both hands.

PMID- 21896004
TI  - The motor repertoire of extremely low-birthweight infants at term in relation to
      their neurological outcome.
AB  - AIM: The aim of this study was to assess the motor repertoire of extremely low
      birthweight infants at term-equivalent age (TEA), in relation to their
      neurological outcome. METHOD: Using Prechtl's method, we assessed both the
      quality of general movements and a detailed motor optimality score in 13
      extremely low-birthweight infants (four males; nine females; mean gestational age
      27.9wks, SD 2.9wks; mean birthweight 798g, SD 129g) at TEA, and related them to
      general movements at the age of 3 months after term and neurological outcome at
      the age of 2 years 6 months. RESULTS: At TEA, 10 of the 13 infants had abnormal
      general movements. All infants showed abnormal leg lifting with extended legs;
      nine showed stiff movements, three showed cramped movements, and two showed
      cramped synchronized general movements. At 3 months, three infants still had
      abnormal general movements. Concurrent movements were abnormal in nine infants
      owing to monotony and jerkiness. Abnormal posture was seen in seven infants. None
      developed cerebral palsy; one infant showed cognitive and motor delay.
      Neurological outcome was not related to general movement quality and optimality
      score at TEA. INTERPRETATION: Abnormal general movements at TEA are common in
      extremely low-birthweight infants. General movements often appear stiff and
      cramped with extended legs. At the age of 3 months after term, general movements
      are mostly normal, but concurrent movements are not. Nevertheless, these
      abnormalities do not imply an impaired neurological outcome such as cerebral
      palsy.

PMID- 21896006
TI  - Are mouse models of human mycobacterial diseases relevant? Genetics says: 'yes!'.
AB  - Relevance and accuracy of experimental mouse models of tuberculosis (TB) are the
      subject of constant debate. This article briefly reviews genetic aspects of this
      problem and provides a few examples of mycobacterial diseases with similar or
      identical genetic control in mice and humans. The two species display more
      similarities than differences regarding both genetics of susceptibility/severity
      of mycobacterial diseases and the networks of protective and pathological immune
      reactions. In the opinion of the author, refined mouse models of mycobacterial
      diseases are extremely useful for modelling the corresponding human conditions,
      if genetic diversity is taken into account.

PMID- 21896007
TI  - The emerging role of HLA-C in HIV-1 infection.
AB  - Recently, genome-wide association studies have identified the major
      histocompatibility complex class I protein HLA-C as an important molecule that
      affects HIV disease progression. The association between HLA-C and HIV disease
      outcome was originally determined through a single nucleotide polymorphism (SNP)
      35 kb upstream of the HLA-C locus. More recent work has focused on elucidating
      the functional significance of the -35 SNP, and several groups now have
      demonstrated HLA-C surface expression to be a key element in control of HIV viral
      load, with higher surface expression associating with slower disease progression.
      Most recently, control of HLA-C surface expression has been correlated with the
      presence of microRNA binding sites that affect HLA-C expression and control of
      HIV disease. This review highlights these results and explores the ways in which
      HLA-C surface expression could affect immune system function in the setting of
      HIV disease.

PMID- 21896009
TI  - Synthetic double-stranded RNA enhances airway inflammation and remodelling in a
      rat model of asthma.
AB  - Respiratory viral infections are frequently associated with exacerbations of
      asthma. Double-stranded RNA (dsRNA) produced during viral infections may be one
      of the stimuli for exacerbation. We aimed to assess the potential effect of dsRNA
      on certain aspects of chronic asthma through the administration of polyinosine
      polycytidylic acid (poly I:C), synthetic dsRNA, to a rat model of asthma. Brown
      Norway rats were sensitized to ovalbumin and challenged three times to evoke
      airway remodelling. The effect of poly I:C on the ovalbumin-induced airway
      inflammation and structural changes was assessed from bronchoalveolar lavage
      fluid and histological findings. The expression of cytokines and chemokines was
      evaluated by real-time quantitative reverse transcription PCR and ELISA.
      Ovalbumin-challenged animals showed an increased number of total cells and
      eosinophils in bronchoalveolar lavage fluid compared with PBS-challenged
      controls. Ovalbumin-challenged animals treated with poly I:C showed an increased
      number of total cells and neutrophils in bronchoalveolar lavage fluid compared
      with those without poly I:C treatment. Ovalbumin-challenged animals showed goblet
      cell hyperplasia, increased airway smooth muscle mass, and proliferation of both
      airway epithelial cells and airway smooth muscle cells. Treatment with poly I:C
      enhanced these structural changes. Among the cytokines and chemokines examined,
      the expression of interleukins 12 and 17 and of transforming growth factor
      beta(1) in ovalbumin-challenged animals treated with poly I:C was significantly
      increased compared with those of the other groups. Double-stranded RNA enhanced
      airway inflammation and remodelling in a rat model of bronchial asthma. These
      observations suggest that viral infections may promote airway remodelling.

PMID- 21896008
TI  - Vitamin D3: a helpful immuno-modulator.
AB  - The active metabolite of vitamin D, 1alpha, 25-dihydroxyvitamin D3 [1,25(OH)(2)
      D3], is involved in calcium and phosphate metabolism and exerts a large number of
      biological effects. Vitamin D3 inhibits parathyroid hormone secretion, adaptive
      immunity and cell proliferation, and at the same time promotes insulin secretion,
      innate immunity and stimulates cellular differentiation. The role of vitamin D3
      in immunoregulation has led to the concept of a dual function as both as an
      important secosteroid hormone for the regulation of body calcium homeostasis and
      as an essential organic compound that has been shown to have a crucial effect on
      the immune responses. Altered levels of vitamin D3 have been associated, by
      recent observational studies, with a higher susceptibility of immune-mediated
      disorders and inflammatory diseases. This review reports the new developments
      with specific reference to the metabolic and signalling mechanisms associated
      with the complex immune-regulatory effects of vitamin D3 on immune cells.

PMID- 21896010
TI  - The Toll-like receptor 1/2 agonists Pam(3) CSK(4) and human beta-defensin-3
      differentially induce interleukin-10 and nuclear factor-kappaB signalling
      patterns in human monocytes.
AB  - Human beta-defensin 3 (hBD-3) activates antigen-presenting cells through Toll
      like receptors (TLRs) 1/2. Several TLR1/2 agonists have been identified but
      little is known about how they might differentially affect cellular activation.
      We compared the effects of hBD-3 with those of another TLR1/2 agonist, Pam(3)
      CSK(4) , in human monocytes. Monocytes incubated with hBD-3 or Pam(3) CSK(4)
      produced interleukin-6 (IL-6), IL-8 and IL-1beta, but only Pam(3) CSK(4) induced
      IL-10. The IL-10 induction by Pam(3) CSK(4) caused down-modulation of the co
      stimulatory molecule, CD86, whereas CD86 expression was increased in monocytes
      exposed to hBD-3. Assessment of signalling pathways linked to IL-10 induction
      indicated that mitogen-activated protein kinases were activated similarly by hBD
      3 or Pam(3) CSK(4) , whereas the non-canonical nuclear factor-kappaB pathway was
      only induced by Pam(3) CSK(4) . Our data suggest that the lack of non-canonical
      nuclear factor-kappaB signalling by hBD-3 could contribute to the failure of this
      TLR agonist to induce production of the anti-inflammatory cytokine, IL-10, in
      human monocytes.

PMID- 21896011
TI  - Long-term carriers generate Epstein-Barr virus (EBV)-specific CD4(+) and CD8(+)
      polyfunctional T-cell responses which show immunodominance hierarchies of EBV
      proteins.
AB  - T cells simultaneously producing multiple cytokines and possessing cytotoxic
      capacity termed polyfunctional cells (PFCs) are increasingly recognized as the
      immune correlate of protection against pathogenic viruses. We investigated co
      expression of four cytokines (interferon-gamma, macrophage inflammatory protein 1
      alpha, tumour necrosis factor-alpha and interleukin-2) and degranulation capacity
      (CD107a surface expression) of Epstein-Barr virus (EBV) -specific CD4(+) and
      CD8(+) T cells upon stimulation by overlapping peptides of EBV lytic (BZLF1) and
      latent (EBNA1, EBNA3 and LMP2) proteins, in 20 healthy Chinese long-term
      carriers. Two patients with post-transplant lymphoproliferative disorder (PTLD),
      who had impaired T-cell immunity, were studied for comparison. Both EBV-specific
      CD4(+) and CD8(+) PFCs were readily generated in long-term carriers and showed
      immunodominance hierarchies of latent proteins (EBNA1 > EBNA3/LMP2 and EBNA3 >
      LMP2 > EBNA1 for CD4(+) and CD8(+) T cells, respectively), as evidenced by a
      higher proportion of PFCs generated by immunodominant EBV proteins than by
      subdominant viral proteins. In contrast, the proportion of EBV-specific PFCs was
      markedly decreased in patients with PTLD. The EBV-specific PFCs produced more
      cytokine per cell than single-functional T cells and comprised different subsets.
      Five-functional CD4(+) and CD8(+) T cells were detected and four-functional
      CD4(+) T cells were mainly CD107a negative and expressed all four cytokines
      whereas four-functional CD8(+) T cells were mainly CD107a positive and expressed
      three of the four cytokines (interleukin-2-negative). We conclude that EBV
      specific PFCs are generated in much higher proportions in the long-term carriers
      than in the patients with PTLD and maintain the immunodominant characteristics of
      the virus.

PMID- 21896012
TI  - Differential modulating effect of natural killer (NK) T cells on interferon-gamma
      production and cytotoxic function of NK cells and its relationship with NK
      subsets in Chlamydia muridarum infection.
AB  - Natural killer T (NKT) cells are a newly identified T-cell population with
      potential immunomodulatory functions. Several studies have shown modulating
      effects of NKT cells activated by alpha-galactosylceramide, a model antigen, on
      NK cell function. We here report a differential modulating effect of NKT cells on
      the interferon-gamma (IFN-gamma) production and cytolytic function of NK cells in
      a chlamydial infection model, using NKT-cell-deficient mice and antibody blocking
      (anti-CD1d monoclonal antibody) approaches. Our results showed that both NKT and
      NK cells became activated and produced IFN-gamma following Chlamydia muridarum
      infection in vitro and in vivo. The NK cells in NKT-cell-deficient mice and CD1d
      blocked mice showed decreased CD69 expression, cellular expansion and IFN-gamma
      production but surprisingly showed increased cytolytic activity (degranulation)
      of immature and more mature NK cell subsets, suggesting an inhibitory role of NKT
      cells on NK cell killing activity. The results suggest that NKT cells
      preferentially promote IFN-gamma production but are inhibitory for the cytotoxic
      function of NK cells in this infection model. Furthermore, the differential
      modulating effect of NKT cells on the IFN-gamma production and cytotoxicity of NK
      cells was observed in immature and mature NK cell subsets, although it was more
      dramatic in the relatively mature CD11b(high)  CD27(high) NK cell subset. This
      finding demonstrates the complexity of innate cell interactions in infection and
      the possible differential impact of NKT cells on the variable functional aspects
      of other cell(s) even in one infection setting.

PMID- 21896013
TI  - Leukotriene C(4) prevents the complete maturation of murine dendritic cells and
      modifies interleukin-12/interleukin-23 balance.
AB  - Leukotriene C(4) is an important mediator in the development of inflammatory
      reactions and ischaemia. Previous studies have shown that leukotriene C(4) is
      able to modulate the function of dendritic cells (DCs) and induce their
      chemotaxis from skin to lymph node. In this study, we decided to evaluate the
      modulation exerted by leukotriene C(4) on DCs, depending on their status of
      activation. We showed for the first time that leukotriene C(4) stimulates
      endocytosis both in immature and lipopolysaccharide (LPS) -activated DCs.
      Moreover, it suppressed the interleukin-12p70 (IL-12p70) release, but induces the
      secretion of IL-23 by DCs activated with LPS and promotes the expansion of T
      helper type 17 (Th17) lymphocytes. Furthermore, blocking the release of IL-23
      reduced the percentages of CD4(+) T cells producing IL-17 in a mixed lymphocyte
      reaction. Ours results suggest that leukotriene C(4) interferes with the complete
      maturation of inflammatory DCs in terms of phenotype and antigen uptake, while
      favouring the release of IL-23, the main cytokine involved in the maintenance of
      the Th17 profile.

PMID- 21896015
TI  - Protective immunity against the gastrointestinal nematode Nippostrongylus
      brasiliensis requires a broad T-cell receptor repertoire.
AB  - The parasitic gastrointestinal nematode Nippostrongylus brasiliensis induces
      massive expansion of T helper type 2 (Th2) cells in the lung and small intestine.
      Th2 cells are a major source of interleukin-4 and interleukin-13, two cytokines
      that appear essential for rapid worm expulsion. It is unclear whether all Th2
      cells induced during infection are pathogen-specific because Th2 cells might also
      be induced by parasite-derived superantigens or cytokine-mediated bystander
      activation. Bystander Th2 polarization could explain the largely unspecific B
      cell response during primary infection. Furthermore, it is not known whether
      protective immunity depends on a polyclonal repertoire of T-cell receptor (TCR)
      specificities. To address these unresolved issues, we performed adoptive transfer
      experiments and analysed the TCR-Vbeta repertoire before and after infection of
      mice with the helminth N. brasiliensis. The results demonstrate that all Th2
      cells were generated by antigen-specific rather than superantigen-driven or
      cytokine-driven activation. Furthermore, we show that worm expulsion was impaired
      in mice with a limited repertoire of TCR specificities, indicating that a
      polyclonal T-cell response is required for protective immunity.

PMID- 21896017
TI  - Quality-of-life assessment: honouring our oath in practice and research.

PMID- 21896014
TI  - Eosinophils elicit proliferation of naive and fungal-specific cells in vivo so
      enhancing a T helper type 1 cytokine profile in favour of a protective immune
      response against Cryptococcus neoformans infection.
AB  - Experimental Cryptococcus neoformans infection in rats has been shown to have
      similarities with human cryptococcosis, because as in healthy humans, rats can
      effectively contain cryptococcal infection. Moreover, it has been shown that
      eosinophils are components of the immune response to C. neoformans infections. In
      a previous in vitro study, we demonstrated that rat peritoneal eosinophils
      phagocytose opsonized live yeasts of C. neoformans, thereby triggering their
      activation, as indicated by the up-regulation of MHC and co-stimulatory molecules
      and the increase in interleukin-12, tumour necrosis factor-alpha and interferon
      gamma production. Furthermore, this work demonstrated that C. neoformans-specific
      CD4(+) and CD8(+) T lymphocytes cultured with these activated C. neoformans
      pulsed eosinophils proliferated, and produced important amounts of T helper type
      1 (Th1) cytokines in the absence of Th2 cytokine synthesis. In the present in
      vivo study, we have shown that C. neoformans-pulsed eosinophils are also able to
      migrate into lymphoid organs to present C. neoformans antigens, thereby priming
      naive and re-stimulating infected rats to induce T-cell and B-cell responses
      against infection with the fungus. Furthermore, the antigen-specific immune
      response induced by C. neoformans-pulsed eosinophils, which is characterized by
      the development of a Th1 microenvironment with increased levels of NO synthesis
      and C. neoformans-specific immunoglobulin production, was demonstrated to be able
      to protect rats against subsequent infection with fungus. In summary, the present
      work demonstrates that eosinophils act as antigen-presenting cells for the fungal
      antigen, hence initiating and modulating a C. neoformans-specific immune
      response. Finally, we suggest that C. neoformans-loaded eosinophils might
      participate in the protective immune response against these fungi.

PMID- 21896018
TI  - A statistics primer.
AB  - Statistical input into an experimental study is often not considered until the
      results have already been obtained. This is unfortunate, as inadequate
      statistical planning 'up front' may result in conclusions which are invalid. This
      review will consider some of the statistical considerations that are appropriate
      when planning a research study.

PMID- 21896016
TI  - Synthetic peptides containing ITIM-like sequences of IREM-1 inhibit BAFF-mediated
      regulation of interleukin-8 expression and phagocytosis through SHP-1 and/or
      PI3K.
AB  - B-cell activation factor of the tumour necrosis factor family (BAFF), an
      important regulator of B-cell survival, has recently been found to be expressed
      on the surface of murine and human macrophages and engagement with its receptor
      was shown to trigger induction of pro-inflammatory mediators and block phagocytic
      activity. In an effort to generate immunomodulatory agents that can regulate BAFF
      mediated signal, decapeptides representing the intracellular immunoreceptor
      tyrosine-based inhibitory motifs (ITIMs) of immune receptor expressed on myeloid
      cells (IREM)-1, an inhibitory transmembrane protein expressed on myeloid cells,
      were synthesized in conjugation with HIV-transactivator of transcription (TAT)(48
      57,) which facilitates the internalization of peptides into cells. Interestingly,
      all five of these synthetic peptides, representing the five ITIM-like sequences
      present in the cytoplasmic tail of IREM-1, exhibited inhibitory action against
      BAFF-mediated induction of matrix metalloproteinase-9 and interleukin-8
      expression. Inhibitor assay and immunoprecipitation assay followed by Western
      blotting demonstrated that the inhibitory action was mediated by Src homology 2
      (SH2)-containing tyrosine phosphatase (SHP)-1 and/or phosphoinositide 3-kinase
      (PI3K). ELISA-based nuclear factor-kappaB DNA binding assay observed that the
      synthetic peptides blocked the activation of nuclear factor-kappaB in an SHP-1
      and phosphoinositide 3-kinase-dependent manner. Three of these synthetic peptides
      exhibited varying degrees of inhibitory action against BAFF-mediated blockage of
      phagocytosis in a SHP-1 and PI3K-dependent manner. These data indicate that the
      synthetic peptides are capable of blocking BAFF-mediated regulation of macrophage
      activities through the activation of SHP-1 and PI3K as well as inhibition of
      nuclear factor-kappaB activation.

PMID- 21896020
TI  - Veterinary surgeons' opinions on dog welfare issues.
AB  - OBJECTIVES: To begin to determine the significance of various dog welfare issues
      as perceived by veterinary practitioners. METHODS: Using an online questionnaire,
      respondents were asked how frequently they were made aware of 12 welfare issues
      and how important they felt each one was for each dog affected. Respondents were
      also asked how much they agreed with statements that the veterinary practitioners
      in their area, and the veterinary profession, should do more about each issue.
      RESULTS: Responses were received from 59 practitioners. The most frequently noted
      problems were "obesity", "chronic pain/poor mobility" and "breed-related
      conditions". The most important issues for each dog affected were "lack of
      treatment for suffering", "abuse or active cruelty" and "malnutrition". "Breed
      related conditions", "obesity" and "behavioural problems" were the issues for
      which there was greatest agreement that veterinary practitioners should do more,
      both in their area and as a profession. CLINICAL SIGNIFICANCE: This pilot study
      suggests that the veterinary profession believes that obesity, breed-related
      conditions and behavioural problems are important concerns, and that more should
      be done about them. Although these results cannot be taken as definitive from a
      study of this size, it does provide a background for such further work involving
      companion dog welfare and the veterinary profession.

PMID- 21896019
TI  - Promoting discussions and decisions about dogs' quality-of-life.
AB  - OBJECTIVE: The objective of this paper is to report the formulation and
      preliminary testing of a participatory tool in order to encourage discussions and
      decisions about dogs' quality-of-life. MATERIALS AND METHODS: A tool was designed
      in which owners rated aspects of their dog's quality-of-life. Two randomised
      controlled trials were conducted: one with a veterinary surgeon who was involved
      in the tool design, the second with other veterinary surgeons. In each, owners
      either were given the tool before a veterinary consultation or underwent normal
      consultations. After each consultation, owners were asked to report what they had
      discussed and what decisions they had made. RESULTS: The study involved a total
      of 170 consultations, of which 91 were randomly allocated to the tool group and
      79 into the control group. In both trials, using the tool was associated with a
      significant increase in the frequency of discussions. In the first trial, using
      the tool was also associated with an increase in the number of decisions made,
      but this was not found in the second trial with practitioners who were not
      involved in the trial design. CLINICAL SIGNIFICANCE: These data suggest that the
      use of a participatory tool has the potential to enhance the effectiveness of
      consultations, especially if the practitioner is familiar with the tool design.

PMID- 21896021
TI  - Mast cell tumour and cutaneous histiocytoma excision wound healing in general
      practice.
AB  - OBJECTIVE: To assess whether wounds from incomplete mast cell tumour excisions
      are at greater risk of healing complications than wounds from complete excisions,
      or cutaneous histiocytomas. METHODS: Mast cell tumours and cutaneous
      histiocytomas submitted to Nationwide Laboratories between November 1, 2007 and
      April 30, 2008 were selected. Questionnaires were sent to submitting
      veterinarians requesting details of tumour characteristics, clinical approach to
      the tumour and wound healing. RESULTS: Three hundred and eighty-six mast cell
      tumours and 524 cutaneous histiocytomas were identified. One hundred and eighty
      five mast cell tumours and 244 cutaneous histiocytomas questionnaires were
      returned (47% response). Wound complications arose in 20% of mast cell tumours
      and 21% of cutaneous histiocytomas. Multivariable analysis confirmed that larger
      tumours, tumours on the feet and a soft/"baggy" appearance, were significantly
      associated with a greater frequency of problems, leading to delayed wound healing
      and dehiscence. CLINICAL SIGNIFICANCE: Incomplete mast cell tumour excision does
      not lead to greater risk of wound complications. Mast cell tumour surgical wounds
      have a similar rate of wound complications as cutaneous histiocytoma wounds.

PMID- 21896022
TI  - Production of an anticanine globulin (polyspecific) reagent for laboratory
      investigation.
AB  - OBJECTIVES: Canine allo- or autoantibodies are clinically important, but
      attachment of these immunoglobulin G (IgG) antibodies does not produce observable
      haemagglutination. Antibody to canine globulins is required to demonstrate
      sensitisation of red blood cells. Commercial reagents are available, but these
      often differ in sensitivity and specificity. Rabbit anticanine globulins
      (polyspecific) were produced for use in canine blood compatibility testing and in
      the investigation of immune-mediated haemolytic anaemia. METHODS: Canine sera was
      pooled, IgG was purified and subsequently used to immunise rabbits. A rising
      titre of anticanine IgG was demonstrated by indirect enzyme-linked immunosorbent
      assay. Rabbit anticanine complement was isolated and investigated by
      agglutination of complement-coated canine red blood cells. Both antibodies were
      purified and checked for crossreactivity before being combined to polyspecific
      anticanine globulins. The obtained reagent was used to indicate sensitised canine
      red blood cells and free antibodies in three different types of clinical samples,
      including blood for compatibility testing and that for investigation of immune
      mediated haemolytic anaemia and screening for post-transfusion alloantibodies and
      was also compared to commercial Coombs' reagent. RESULTS: The product provided
      results in accordance with those from commercial Coombs' reagent. The sensitivity
      for canine crossmatching was 100% and specificity for diagnosing immune-mediated
      haemolytic anaemia was 87%. CLINICAL SIGNIFICANCE: This product is helpful for
      canine crossmatching purposes and in the investigation of immune-mediated
      haemolytic anaemia.

PMID- 21896023
TI  - Ultrasonography of small intestinal obstructions: a contemporary approach.
AB  - OBJECTIVES: To assess the accuracy of intestinal ultrasound for diagnosis of
      intestinal obstruction in dogs and cats. METHODS: A prospective clinical study
      was performed. Inclusion criteria were dogs and cats with clinical signs
      suggestive of gastrointestinal obstruction. Animals with no obstruction detected
      on ultrasound were excluded if they could not be monitored for 48 hours to
      confirm absence of obstruction. Sonographic diagnosis of small intestinal
      obstruction was based on identification of at least two findings suggestive of
      intestinal obstruction. RESULTS: Ninety-two patients suspected of having
      intestinal obstruction were included. Correct diagnosis of intestinal obstruction
      was made in 21 cases (23%), and in 68 (74%) this diagnosis was excluded.
      Interpretation of the images on prospective analysis had sensitivity, positive
      predictive, specificity and negative predictive values of 100%, 87.5%, 95.8% and
      100%, respectively. CLINICAL SIGNIFICANCE: Ultrasonography is an excellent method
      for investigation of animals with gastrointestinal disorders, and is particularly
      useful for excluding obstructive processes.

PMID- 21896028
TI  - B19: benign or not?

PMID- 21896029
TI  - A window of opportunity: the aggressive use of plasma in early resuscitation.

PMID- 21896030
TI  - Transfusion medicine illustrated: therapeutic plasma exchange in
      hypertriglyceridemic pancreatitis.

PMID- 21896032
TI  - New K103 beta3 allele identified in a context of severe neonatal
      thrombocytopenia.
AB  - BACKGROUND: A new beta3 allele was identified in a severe case of neonatal
      alloimmune thrombocytopenia (<7 * 10(9) /L). STUDY DESIGN AND METHODS: Diagnosis
      was done by use of monoclonal antibody-specific immobilization of platelet (PLT)
      antigen for serologic analyses and polymerase chain reaction (PCR)-sequence
      specific primers (SSP) and PCR-restriction fragment length polymorphism (RFLP)
      for genotyping. Direct sequencing of PCR product was done and mutant
      alphaIIbbeta3 expressed in HEK-293 cells. RESULTS: Serologic analysis revealed in
      the maternal serum an anti-human PLT alloantigen (HPA)-1a alloantibody associated
      to an anti-alpha2beta1. Anti-HPA-1a alloimmunization diagnosis was confirmed by
      genotyping showing maternofetal incompatibility. However, investigation of rare
      HPA polymorphisms revealed discrepant HPA-16b assignation between PCR-RFLP and
      PCR-SSP. Sequencing revealed a new c.385C>A mutation in the beta3 coding sequence
      resulting in a false assignation of the HPA-16b allele by PCR-RFLP. This mutation
      leads to a Q103K substitution in mature beta3. The K103-beta3 form of the complex
      was expressed in HEK-293 cells but did not react with the maternal serum.
      CONCLUSION: We have characterized a new rare allele (frequency < 1%) of beta3
      that yields false HPA-16b genotyping in PCR-RFLP. This new case of false typing
      assignation emphasizes the necessity to use two genotyping techniques in
      diagnosis. This particularly applies for rare HPA polymorphisms when PLT
      phenotyping cannot be used.

PMID- 21896033
TI  - Sensitivity comparison of two Food and Drug Administration-licensed, triplex
      nucleic acid test automated assays for hepatitis B virus DNA detection and
      associated projections of United States yield.
AB  - BACKGROUND: There have been no comparisons of the relative sensitivity of the two
      Food and Drug Administration-licensed multiplex (MPX) nucleic acid test (NAT)
      systems (Procleix Ultrio [Gen-Probe], TIGRIS platform [Novartis]; and cobas
      TaqScreen MPX [Roche Molecular Systems], cobas s 201 platform [Roche Instrument
      Center]) for detecting hepatitis B virus (HBV)-infected donors in minipool sizes
      (MP) used in the United States. STUDY DESIGN AND METHODS: Routine blood samples
      from Thailand were obtained from plasma units from 129 hepatitis B surface
      antigen (HBsAg)-negative, HBV NAT-yield donations. Blinded US testing included
      antibody to hepatitis B core antigen (anti-HBc), NAT using both manufacturers'
      systems (undiluted-individual donation [ID], in singlet and diluted 1:6 and 1:16
      in triplicate), quantitative antibody to hepatitis B surface antigen, HBV DNA
      viral loads, and HBV genotyping. HBV yields in the United States were estimated
      using the incidence/window period (WP) model and compared to the calculated assay
      sensitivities. RESULTS: Eighty samples were classified as occult HBV (anti-HBc
      reactive) and 49 as WP (anti-HBc nonreactive). For US pool sizes, MPX detected
      significantly more samples than Ultrio (MPX MP6 vs. Ultrio MP16; p < 0.0001 for
      occult and WP). Ultrio MP16 results were not statistically different from Ultrio
      MP6 (p = 0.68 for occult; p = 0.42 for WP). There was no difference between
      platforms for MP sizes used in most of the world (MPX MP6 vs. Ultrio ID; p = 0.70
      for occult and p = 0.34 for WP). Viral loads were higher in WP samples. Modeled
      yield estimates were consistent with measured assay sensitivity on the Thai donor
      samples. CONCLUSIONS: As used in the United States, MPX MP6 is more sensitive
      than Ultrio MP16, but the impact of this difference is mitigated by low numbers
      of HBV WP infections.

PMID- 21896034
TI  - Cord (placental) blood storage: extent and functional aspects.

PMID- 21896037
TI  - Peripheral blood mononuclear cells obtained from leukoreduction system chambers
      show better viability than those from leukapheresis.

PMID- 21896038
TI  - Cord blood collection after cesarean section improves banking efficiency.

PMID- 21896039
TI  - Radiographs and CBCT--time for a reassessment?

PMID- 21896040
TI  - Application of transient elastography in chronic hepatitis B.

PMID- 21896042
TI  - Microscopic colitis and disease associations.

PMID- 21896044
TI  - Erosive oesophagitis with particular reference to Asians.

PMID- 21896047
TI  - Editor's choice. The cultural relevance of research instruments.

PMID- 21896046
TI  - Inaccuracies concerning Salofalk granules.

PMID- 21896048
TI  - Requirement of alveolar bone formation for eruption of rat molars.
AB  - Tooth eruption is a localized event that requires a dental follicle (DF) to
      regulate the resorption of alveolar bone to form an eruption pathway. During the
      intra-osseous phase of eruption, the tooth moves through this pathway. The
      mechanism or motive force that propels the tooth through this pathway is
      controversial but many studies have shown that alveolar bone growth at the base
      of the crypt occurs during eruption. To determine if this bone growth
      (osteogenesis) was causal, experiments were designed in which the expression of
      an osteogenic gene in the DF, bone morphogenetic protein-6 (Bmp6), was inhibited
      by injection of the first mandibular molar of the rat with a small interfering
      RNA (siRNA) targeted against Bmp6. The injection was followed by electroporation
      to promote uptake of the siRNA. In 45 first molars injected, eruption was either
      delayed or completely inhibited (seven molars). In the impacted molars, an
      eruption pathway formed but bone growth at the base of the crypt was greatly
      reduced compared with the erupted first-molar controls. These studies show that
      alveolar bone growth at the base of the crypt is required for tooth eruption and
      that Bmp6 may be essential for promoting this growth.

PMID- 21896049
TI  - Effect of interleukin-17 on the expression of chemokines in gingival epithelial
      cells.
AB  - The role of interleukin (IL)-17 in cellular communication in inflammation has
      been well described, and a positive correlation between the severity of
      periodontitis and the level of IL-17 was reported. Although epithelial cells are
      a major target of IL-17, little is known about the effect of IL-17 on the
      production of chemokines by human gingival epithelial cells (HGECs). We evaluated
      the effects of IL-17 on the expression of CXCL8 and CCL2 by HGECs using
      quantitative real-time PCR and ELISA. In addition, the role of the nuclear factor
      (NF)-kappaB signalling pathway in the IL-17-mediated expression of chemokines was
      assessed using a specific inhibitor. Stimulation with IL-17 up-regulated the
      expression of CXCL8 mRNA but not of CCL2 mRNA in HGECs, whereas tumour necrosis
      factor-alpha (TNF-alpha) elevated the expression of mRNA for both chemokines.
      Stimulation with IL-17 up-regulated the secretion of CXCL8 protein, but not the
      secretion of CCL2 protein. The effect of IL-17 on CXCL8 production was suppressed
      using an anti-IL-17R Ig, suggesting a role for a specific receptor-ligand
      interaction. Inhibition of the NF-kappaB signalling pathway demonstrated that NF
      kappaB activation is required for the CXCL8 expression in HGECs. In conclusion,
      IL-17 is involved in the regulation of the innate immune response in HGECs by
      inducing CXCL8 production.

PMID- 21896050
TI  - Involvement of angiotensin II type 1 receptors in interleukin-1beta-induced
      interleukin-6 production in human gingival fibroblasts.
AB  - The renin-angiotensin system is thought to be involved in inflammatory processes
      such as periodontitis. However, its precise role is still unclear. Therefore, in
      the present study the expression of the angiotensin II type 1 receptor (AT1R) was
      investigated in inflamed human gingival tissue, and the possible involvement of
      the AT1R in interleukin-1beta (IL-1beta)-induced interleukin-6 (IL-6) production
      by cultured human gingival fibroblasts (HGFs) was also studied.
      Immunohistochemical staining revealed that inflammatory cells and fibroblast-like
      cells were positive for the AT1R. However, in healthy gingival tissue, AT1R
      staining was very weak. The levels of AT1R mRNA and AT1R protein increased in
      HGFs after stimulation with IL-1beta. The levels of IL-1beta-induced IL6 mRNA and
      IL-6 protein were significantly reduced in AT1R gene-silenced HGFs compared with
      control HGFs. The data suggest that the AT1R may be involved in the regulation of
      gingival inflammation by modulating IL-1beta-induced IL-6 production in HGFs.

PMID- 21896051
TI  - Impairment of acetylcholine-mediated endothelium-dependent relaxation in isolated
      parotid artery of the alloxan-induced diabetic rabbit.
AB  - The aim of this study was to assess the effect of type 1 diabetes mellitus
      (induced by a single intravenous injection of 100 mg kg(-1) of alloxan) on
      acetylcholine (ACh)-induced relaxation in isolated rabbit parotid gland feeding
      artery. Isometric force measurements and quantification of inducible nitric oxide
      synthase (iNOS) mRNA by real-time RT-PCR were made in parotid artery rings from
      diabetic and control rabbits. Acetylcholine induced concentration- and
      endothelium-dependent vasorelaxation that was significantly decreased in parotid
      artery rings from diabetic rabbits. Schild analysis of the ACh vasorelaxant
      effect, in the presence of selective muscarinic receptor antagonists, revealed
      involvement of the M(3) receptor subtype in parotid artery rings from both
      control and diabetic rabbits, with no change in antagonist affinity constants.
      The inhibitory effects of indomethacin, a non-selective inhibitor of
      cyclooxygenase, and of high potassium, an inhibitor of hyperpolarization, on ACh
      vasorelaxation were increased. The effect of N(G) -nitro-l-arginine, a non
      selective inhibitor of NOS, was decreased in diabetes. S-methylisothiourea, a
      selective inhibitor of iNOS, significantly reduced ACh vasorelaxation only in
      parotid artery rings from diabetic rabbits. Also, up-regulation of iNOS mRNA
      expression was detected in parotid artery rings from diabetic rabbits. These
      results suggest that in parotid artery rings from diabetic rabbits, impaired
      endothelium-dependent vasorelaxation to ACh appears to be caused by the loss of a
      nitric oxide-mediated component and increased iNOS expression, and is unlikely to
      be caused by a change at the M(3) receptor level.

PMID- 21896052
TI  - A test of Berggren's model of dental fear and anxiety.
AB  - Berggren's (1984) model of dental fear and anxiety predicts that dentally anxious
      individuals postpone treatment, leading to a deteriorating dental state and
      subsequently to fear of negative evaluations in relation to their oral condition.
      The present study aimed to test one of the core assumptions of this model, namely
      that deterioration of dental health status would mediate the effects of avoidance
      of dental care on self-reported fear of negative evaluation. Participants were 73
      patients (mean age 38.5 yr) meeting the diagnostic and statistical manual of
      mental disorders - 4th edn - Text Revision (DSM-IV-TR) criteria of dental phobia.
      Variables in the theoretical model were operationalized with multiple measures. A
      series of Sobel tests indicated that mediation was present for the relationship
      between years of avoidance and fear of negative self-evaluation when dental
      health status was based on the assessment of dentists or patients' opinion of
      their own dental state, but not when dental health status was operationalized as
      decayed, missing or filled surfaces (DMFS). Although the findings are supportive
      of Berggren's model, other causal pathways that contribute to the perpetuation of
      anxiety and fear still need to be tested. The results suggest that individuals
      with high levels of dental anxiety would particularly benefit from interventions
      specifically designed to break their avoidance pattern.

PMID- 21896054
TI  - 'Making dental care possible: a mutual affair': a grounded theory relating to
      adult patients with dental fear and regular dental treatment.
AB  - Dental fear is a common and widespread problem, which can cause severe stress.
      Even so, most patients with dental fear undergo regular dental treatment in spite
      of their fear and many enjoy good oral health. The aim of this study was to
      obtain a deeper understanding of how patients with dental fear manage to undergo
      dental treatment. Fourteen patients with dental fear, who undergo regular dental
      care, were interviewed. Qualitative analysis of the transcribed interviews was
      performed according to the principles of grounded theory. A conceptual framework
      was generated, and the main concern was identified as 'making dental care
      possible - a mutual affair'. Four additional categories explained how patients
      handled their dental fear and how dental care became possible. The strategies
      were labelled 'taking part in a mental wrestling match', 'trust-filled
      interaction with dental staff', 'striving for control' and 'seeking and/or
      receiving social support'. The results showed that making dental care possible
      for patients with dental fear is a mutual challenge that requires interplay
      between dental staff and patients, involving verbal and non-verbal communication
      reflecting respect, attention, and empathy. Moreover, a balance between nearness
      and distance and between professional and personal treatment is required.

PMID- 21896053
TI  - Personality and oral health.
AB  - We investigated age-26 personality characteristics and age-32 oral health in a
      prospective study of a complete birth cohort born in Dunedin, New Zealand.
      Personality was measured using the Multidimensional Personality Questionnaire
      (MPQ). Oral health was measured using the short-form Oral Health Impact Profile
      (OHIP-14), a global measure, and dental examinations. Personality profiles were
      constructed for 916 individuals (50.8% men) using standardized MPQ scores, and
      multivariate analyses examined their association with oral health. Those
      reporting 1+ OHIP-14 impacts had higher Negative Emotionality scores (and lower
      Constraint and Positive Emotionality MPQ superfactor scores) than those who did
      not. After controlling for gender, clinical status, and the other two MPQ
      superfactors, those scoring higher on Negative Emotionality had a greater risk of
      reporting 1+ OHIP-14 impacts, as well as 3+ OHIP-14 impacts and worse-than
      average oral health. They also had a greater risk of having lost at least one
      tooth from caries and of having 3+ decayed surfaces. Personality characteristics
      appear to shape self-reports of oral health. Personality is also a risk factor
      for clinical disease status, at least with respect to dental caries and its
      sequelae. Because the attitudes and values tapped into by personality tests can
      be altered by brief cognitive interventions, those might be useful in preventive
      dentistry.

PMID- 21896055
TI  - Dental caries in adolescents with attention deficit hyperactivity disorder: a
      population-based follow-up study.
AB  - This study tested the hypothesis that adolescents with attention deficit
      hyperactivity disorder (ADHD) exhibit a higher prevalence of caries than
      adolescents in a control group. Thirty-two adolescents with ADHD and a control
      group of 55 adolescents from a population-based sample, all 17 yr of age,
      underwent a clinical and radiographic dental examination. The mean +/- SD number
      of decayed surfaces (DS) was 2.0 +/- 2.2 in adolescents with ADHD and 0.9 +/- 1.4
      in adolescents of the control group. Thirty-one per cent of the adolescents in
      the ADHD group had no new caries lesions (DS = 0) compared with 62% in the
      control group. Six per cent of the adolescents in the ADHD group were caries free
      [decayed, missing or filled surfaces (DMFS) = 0] compared with 29% in the control
      group. Adolescents with ADHD also had a higher percentage of gingival sites that
      exhibited bleeding on probing compared with the control group: 35 +/- 39% vs. 16
      +/- 24% (mean +/- SD), respectively. At 17 yr of age, adolescents with ADHD
      exhibited a statistically significantly higher prevalence of caries compared with
      an age-matched control group. Adolescents with ADHD need more support regarding
      oral hygiene and dietary habits. They should be followed up with shorter
      intervals between dental examinations to prevent caries progression during
      adulthood.

PMID- 21896056
TI  - Prevalence and risk factors of sleep bruxism and wake-time tooth clenching in a 7
      to 17-yr-old population.
AB  - Sleep-related bruxism (SB) and wake-time tooth clenching (TC) have been
      associated with temporomandibular disorders (TMDs), headache, and sleep and
      behavioral complaints. This study aimed to assess the prevalence and risk factors
      of these signs and symptoms in a 7- to 17-yr-old population (n = 604) seeking
      orthodontic treatment. Data were collected by questionnaire and by a clinical
      examination assessing craniofacial morphology and dental status. Sleep-related
      bruxism was reported by 15% of the population and TC was reported by 12.4%. The
      SB group (n = 58) was mainly composed of children (67.3% were <=12 yr of age) and
      the TC group (n = 42) was mainly composed of adolescents (78.6% were >=13 yr of
      age). The craniofacial morphology of over 60% of SB subjects was dental class II
      and 28.1% were a brachyfacial type. Compared with controls (n = 220), SB subjects
      were more at risk of experiencing jaw muscle fatigue [adjusted OR (AOR) = 10.5],
      headache (AOR = 4.3), and loud breathing during sleep (AOR = 3.1). Compared with
      controls, TC subjects reported more temporomandibular joint clicking (AOR = 5),
      jaw muscle fatigue (AOR = 13.5), and several sleep and behavioral complaints.
      Sleep- and wake-time parafunctions are frequently associated with signs and
      symptoms suggestive of TMDs, and with sleep and behavioral problems. Their
      clinical assessment during the planning of orthodontic treatment is recommended.

PMID- 21896057
TI  - Influence of oxygen inhibition on the surface free-energy and dentin bond
      strength of self-etch adhesives.
AB  - We compared the surface free-energies and dentin bond strengths of single-step
      self-etch adhesives with and without an oxygen-inhibited layer. The labial dentin
      surfaces of bovine mandibular incisors were wet ground with #600-grit silicon
      carbide paper. The adhesives were applied to the ground dentin, light-irradiated,
      and the oxygen-inhibited layer was either retained or removed with ethanol. The
      surface free-energies were determined by measuring the contact angles of three
      test liquids placed on the cured adhesives. The dentin bond strengths of
      specimens with and without the oxygen-inhibited layer were measured. For all
      surfaces, the value of the estimated surface tension component was relatively
      constant at 35.5-39.8 mJ m(-2) . The value of the , Lewis acid component
      increased slightly when the oxygen-inhibited layer was removed, whereas that of
      the , Lewis base component decreased significantly. The bond strengths of the
      self-etch adhesives were significantly lower in specimens without an oxygen
      inhibited layer (13.2-13.6 MPa) than in those with an oxygen-inhibited layer
      (17.5-18.4 MPa). These results indicate that the presence of an oxygen-inhibited
      layer in single-step self-etch adhesives with advanced photoinitiators promotes
      higher dentin bond strength.

PMID- 21896058
TI  - Zinc-doped dentin adhesive for collagen protection at the hybrid layer.
AB  - The aim of the study was to ascertain whether the addition of zinc to adhesives
      may decrease metalloproteinase-mediated collagen degradation without affecting
      bonding efficacy. Human dentin beams were treated with phosphoric acid, with
      Clearfil SE Bond Primer or with Clearfil SE Bond Primer plus ZnCl(2) (2 wt%).
      Acid-etched dentin was infiltrated with Single Bond, Single Bond plus ZnCl(2) (2
      wt%), or Single Bond plus ZnO nanoparticles (10 wt%), and Clearfil SE Bond-primed
      dentin was infiltrated with Clearfil SE Bonding resin, Clearfil SE-Bonding resin
      with ZnCl(2) (2 wt%), or Clearfil SE-Bonding resin with ZnO nanoparticles (10
      wt%). The C-terminal telopeptide concentrations were determined 24 h, and 1 and 4
      wk after treatment. Microtensile bond strength to dentin was determined for the
      tested adhesives. Matrix metalloproteinases-mediated collagen degradation
      occurred in acid-etched and SE-primed dentin. Resin infiltration decreased
      collagen degradation. Lower collagen degradation was found for SE Bond than for
      Single Bond. Zinc-doped Single Bond resin always reduced collagen degradation,
      the ZnO particles being more effective than ZnCl(2) . Zinc-doped SE Bond reduced
      the liberation of C-terminal telopeptide only at 24 h. Bond strength to dentin
      was not decreased when Zn-doped resins were employed, except when ZnCl(2) was
      added to SE Primer. Zinc-doped resin reduced collagen degradation in Single Bond
      hybrid layers, but did not affect bond strength. The addition of zinc to SE Bond
      had no beneficial effects.

PMID- 21896059
TI  - Co-development of proprioceptive afferents and the corticospinal tract within the
      cervical spinal cord.
AB  - In maturity, skilled movements depend on coordination of control signals by
      descending pathways, such as the corticospinal tract (CST), and proprioceptive
      afferents (PAs). An important locus for this coordination is the spinal cord
      intermediate zone. Convergence of CST and PA terminations onto common regions
      leads to interactions that may underlie afferent gating and modulation of
      descending control signals during movements. We determined establishment of CST
      and PA terminations within common spinal cord regions and development of synaptic
      interactions in 4-week-old cats, which is before major spinal motor circuit
      refinement, and two ages after refinement (weeks 8, 11). We examined the
      influence of one or the other system on monosynaptic responses, on the spinal
      cord surface and locally in the intermediate zone, evoked by either CST or deep
      radial nerve (DRN) stimulation. DRN stimulation suppressed CST monosynaptic
      responses at 4 weeks, but this converted to facilitation by 8 weeks. This may
      reflect a strategy to limit CST movement control when it has aberrant immature
      connections, and could produce errant movements. CST stimulation showed delayed
      development of mixed suppression and facilitation of DRN responses. We found
      development of age-dependent overlap of PA and CST terminations where
      interactions were recorded in the intermediate zone. Our findings reveal a novel
      co-development of different inputs onto common spinal circuits and suggest a
      logic to CST-PA interactions at an age before the CST has established
      connectional specificity with spinal circuits.

PMID- 21896060
TI  - Tinnitus: where is the source (Commentary on Vanneste et al.).

PMID- 21896061
TI  - Between-systems memory interference during retrieval.
AB  - Context memories normally depend on the hippocampus (HPC) but, in the absence of
      the HPC, other memory systems are capable of acquiring and supporting these
      memories. This suggests that the HPC can interfere with other systems during
      memory acquisition. Here we ask whether the HPC can also interfere with the
      retrieval of a context memory that was independently acquired by a non-HPC
      system. Specifically, we assess whether the HPC can impair the retrieval of a
      contextual fear-conditioning memory that was acquired while the HPC was
      temporarily inactive. Rats were infused with the gamma-aminobutyric acid
      (GABA)(A) receptor agonist muscimol in the dorsal and ventral HPC either before
      acquisition, retrieval, or prior to both acquisition and retrieval, consistent
      with the effects of permanent HPC lesions on contextual fear conditioning, if the
      HPC was inactive at the time of acquisition and retention memory was intact.
      Thus, non-HPC systems acquired and supported this memory in absence of the HPC.
      However, if the HPC was inactive during acquisition but active thereafter, rats
      displayed severe deficits during the retention test. Moreover, when the same rats
      received a second retention test but with the HPC inactive at this time, the
      memory was recovered, suggesting that removal of a form of interference allowed
      the memory to be expressed. Combined, these findings imply that the HPC competes
      and/or interferes with retrieval of a long-term memory that was established in
      non-HPC systems.

PMID- 21896062
TI  - Cocaine self-administration leads to alterations in temporal responses to cocaine
      challenge in limbic and motor circuitry.
AB  - Chronic use of cocaine is associated with lasting alterations in brain
      metabolism, circuitry, and receptor properties. We used neuroimaging with
      pharmacological magnetic resonance imaging to assess alterations in response to
      cocaine (0.5 mg/kg) in animals trained to self-administer cocaine on a fixed
      ratio 5 schedule of reinforcement, as well as saline-yoked controls, after 28
      days of cocaine abstinence. We fitted the cerebral blood volume (CBV) curves for
      full-width half-maximum (FWHM) as well as peak CBV response. There were
      significant increases in the FWHM of the response curves in the cocaine self
      administering (SA) animals as compared with saline-yoked controls in the medial
      prefrontal cortex (mPFC) and the caudate/putamen (CPu), and increases in peak CBV
      in the M1 motor cortex, CPu, and pedunculopontine tegmental nucleus. Functional
      connectivity analysis showed increased correlations in the cocaine SA rats upon
      acute cocaine challenge, especially in the S1, mPFC, and thalamus. As D3 receptor
      expression is postulated to increase following chronic cocaine administration, we
      also examined the response to 0.2 mg/kg of the D3-preferring agonist 7-hydroxy
      N,N-di-n-propyl-2-aminotetralin (7-OHDPAT). Cocaine SA animals showed a decreased
      overall CBV response to this drug, except in the globus pallidus. The
      hypothalamus showed a negative CBV change in response to cocaine challenge,
      similar to that noted with the D3 agonist, and showed a smaller response in the
      cocaine SA animals than in the controls. Given the good coupling of cerebral
      hemodynamics with dopamine dynamics previously observed with pharmacological
      magnetic resonance imaging, these data suggest that increased persistence of
      dopamine in the prefrontal cortex may be responsible for some of the behavioral
      alterations observed subsequent to chronic cocaine use.

PMID- 21896066
TI  - The relationship between alcohol and violence: population, contextual and
      individual research approaches.

PMID- 21896067
TI  - Alcohol and homicide in the United States: is the link dependent on wetness?
AB  - INTRODUCTION AND AIMS: Several aggregate-level studies have suggested that the
      relationship between alcohol and homicide is stronger in countries with an
      intoxication-oriented drinking pattern than in countries where drinking is more
      tempered. The present paper extends this research tradition by analysing the
      alcohol-homicide link in various regions in the USA. DESIGN AND METHODS: I used
      annual time-series data for the US states covering the period 1950-2002. Alcohol
      sales figures were used as proxy for alcohol consumption. Mortality data were
      used as indicators of homicide. The states were sorted into three groups labelled
      Dry, Moderate and Wet, where the last group has the highest prevalence of
      hazardous drinking according to survey data. Group-specific data were analysed
      using (i) autoregressive integrated moving average (ARIMA) modelling and (ii)
      fixed effects modelling. All modelling was based on differenced data, thus
      eliminating time trends and interstate correlations, both of which may bias
      estimates. RESULTS: The ARIMA estimates displayed a statistically significant
      gradient in alcohol effects; the effect was strongest in Wet, and weakest and
      insignificant in Dry states. The fixed-effects estimates showed a corresponding
      pattern, although the gradient was less steep and insignificant. The gradient was
      also weakened if the effects were expressed in absolute rather than relative
      terms. The spatial pattern revealed no ecological correlation between alcohol and
      homicide. DISCUSSION AND CONCLUSIONS: Results provided mixed support for the
      hypothesis that the relationship between alcohol and homicide is stronger in wet
      than in dry states in the USA. Future research should probe more specific
      indicators of homicide as well as alcohol consumption.

PMID- 21896068
TI  - Population drinking and homicide in Australia: a time series analysis of the
      period 1950-2003.
AB  - BACKGROUND: Despite a significant amount of research on alcohol and homicide in
      Australia, as yet there has been no study of the association at the aggregate
      level to reveal where Australia fits in with respect to the cultural differences
      found in the international research of this association. Aims. To analyse the
      temporal association between population drinking and homicide in Australia and to
      put the results in an international comparative perspective. METHOD: Using
      Autoregressive Integrated Moving Average (ARIMA) time series analysis, overall
      and gender-specific homicide rates from 1950 to 2003 were analysed in relation to
      alcohol consumption overall as well as to different beverages. FINDINGS: A one
      litre increase in per capita consumption was followed by an 8% increase in
      overall and male homicide rates and a 6% increase in female homicide rates. The
      effect was mainly driven by beer consumption. In a comparative perspective, the
      importance of population drinking was similar to what has been found in Western
      Europe. Conclusions. Australia belongs to the group of countries where lowering
      population drinking is likely to be associated with lower homicide rates and
      reducing beer consumption seems to be the most efficient way to achieve this.

PMID- 21896069
TI  - Per capita alcohol consumption and suicide mortality in a panel of US states from
      1950 to 2002.
AB  - introduction and aims: The relationship between per capita alcohol consumption
      and suicide rates has been found to vary in significance and magnitude across
      countries. This study utilises a panel of time-series measures from the US states
      to estimate the effects of changes in current and lagged alcohol sales on suicide
      mortality risk. DESIGN AND METHODS: Generalised least squares estimation utilised
      53 years of data from 48 US states or state groups to estimate relationships
      between total and beverage-specific alcohol consumption measures and age
      standardised suicide mortality rates in first-differenced semi-logged models.
      RESULTS: An additional litre of ethanol from total alcohol sales was estimated to
      increase suicide rates by 2.3% in models utilising a distributed lag
      specification while no effect was found in models including only current alcohol
      consumption. A similar result is found for men, while for women both current and
      distributed lag measures were found to be significantly related to suicide rates
      with an effect of approximately 3.2% per litre from current and 5.8% per litre
      from the lagged measure. Beverage-specific models indicate that spirits is most
      closely linked with suicide risk for women while beer and wine are for men.
      Unemployment rates are consistently positively related to suicide rates.
      DISCUSSION AND CONCLUSIONS" Results suggest that chronic effects, potentially
      related to alcohol abuse and dependence, are the main source of alcohol's impact
      on suicide rates in the USA for men and are responsible for about half of the
      effect for women.

PMID- 21896070
TI  - Alcohol's role in sexual violence perpetration: theoretical explanations,
      existing evidence and future directions.
AB  - ISSUES: There is controversy regarding the extent to which alcohol plays a causal
      role in sexual assault perpetration. APPROACH: This paper critically reviews the
      relevant alcohol administration and survey research literature. KEY FINDINGS:
      Alcohol administration researchers have randomly assigned male participants to
      drink conditions prior to exposure to an acquaintance rape scenario. As compared
      to sober participants, intoxicated participants find the male character's use of
      force to obtain sex more acceptable and express greater willingness to act in a
      similar manner. In several studies, these effects are strongest for intoxicated
      men with hostile attitudes toward women. Survey researchers have asked male
      participants to describe incidents in which they behaved in a sexually aggressive
      manner. Men who commit sexual assault when drinking report having traits,
      attitudes and experiences similar to those of other perpetrators except in the
      alcohol domain. Perpetrators who commit sexual assault when drinking tend to
      drink more than other perpetrators in sexual situations and have stronger
      expectancies regarding alcohol's effects on sexual behaviour. IMPLICATIONS:
      Overall, research suggests that alcohol interacts with personality and aspects of
      the situation, adding to the risk of perpetration among men already predisposed
      to engaging in sexual aggression. CONCLUSIONS: Although there are no simple
      answers to questions about alcohol's role in sexual assault, research suggests
      that intoxication may be a more important determinant of when some men commit
      sexual aggression, rather than who becomes sexually aggressive.

PMID- 21896071
TI  - Heavy drinking and the disposition of intimate partner violence cases in French
      courts.
AB  - INTRODUCTION AND AIMS: In 1992, France passed a specific penal law on intimate
      partner violence. The present study explores the functioning of this new law by
      examining the characteristics of perpetrators in cases that were tried rather
      than dismissed. Additionally, the characteristics of heavy drinkers were compared
      with those of non-heavy drinkers. DESIGN AND METHODS: We analysed all cases of
      intimate partner violence processed in the years 1999-2000 by a major court of
      the Paris metropolitan area. Data were collected on 223 perpetrators (all 166
      tried perpetrators and 10% of the 570 perpetrators whose case was dismissed) and
      how cases were handled institutionally. Logistic regression was used to identify
      perpetrator characteristics significantly associated with being tried (vs.
      dismissed) and being a heavy drinker. RESULTS: Being tried was significantly more
      likely if the perpetrator had inflicted an injury, engaged in prior aggression
      and was a heavy drinker. Heavy drinking perpetrators were significantly more
      likely than non-heavy drinkers to have been drinking before the act. They were
      less likely to be under 40, more likely to be French, part of a stable couple and
      to have engaged in various types of prior aggression. DISCUSSION AND CONCLUSIONS:
      In 2000, heavy drinking was associated with increased risk of being tried and
      with drinking before the act. Heavy drinkers are more likely to have committed
      all forms of aggression, but only verbal aggression is significant. In 2000,
      judges gave heavy drinkers harsher sentences and a 2007 law sanctioned them even
      more severely. Our results suggest that treatment focused on problem drinking
      could be a helpful response-perhaps more so than harsher sentences-to intimate
      partner violence.

PMID- 21896072
TI  - The impact of retail practices on violence: the case of single serve alcohol
      beverage containers.
AB  - INTRODUCTION AND AIMS: This paper examines the role that sales of single serve
      alcoholic beverages plays in violent crime in surrounding areas. Increasingly a
      target of regulatory measures, this is the first study to systematically assess
      the impact of single serve containers on neighbourhood violence. DESIGN AND
      METHODS: The relative proportion of shelf space in each liquor establishment in
      San Bernardino, CA devoted to single serve alcohol containers was surveyed.
      Assuming that this is a rough indicator of the amount of sales derived from
      single serve containers, we use this indicator as a measure of the impact of
      specific retail practice on violence around the outlet. RESULTS: Results show
      that the average proportion of shelf space devoted to single serve containers in
      the unit of analysis, the US Census Bureau block group, was positively related to
      violent crime, net of overall retail availability of alcohol and relevant social
      and economic indicators often used to predict violent crime rates in such units.
      DISCUSSION AND CONCLUSIONS: These findings suggest that if the city were to make
      the voluntary ban on single serve container sales mandatory, violence in the
      surrounding areas would decline, all other things being equal. This study
      provides a much more grounded and specific justification for enacting such policy
      changes and once again shows the utility of alcohol policy for the reduction of
      crime and violence.

PMID- 21896073
TI  - Alcohol availability and youth homicide in the 91 largest US cities, 1984-2006.
AB  - The aggregate relationship between homicide and alcohol availability is well
      established across a number of national and sub-national settings in North
      America, Europe and some parts of Asia. However, results linking youth homicide
      and alcohol availability at the retail level are largely absent from the
      literature, especially at the city level and across longer time periods. In a
      multivariate, pooled time series and cross-section study, youth homicide
      offending rates for two age groups, 13-17 and 18-24, were analysed for the 91
      largest cities in the USA between 1984 and 2006. Data for social and economic
      characteristics, drug use, street gang activity and gun availability were also
      used as time series measures. Data on the availability of alcohol for each city
      were gathered from the US Census of Economic Activity, which is conducted every 5
      years. These data were used to construct an annual time series for the density of
      retail alcohol outlets in each city. Results indicated that net of other
      variables, several of which had significant impacts on youth homicide, the
      density of alcohol outlets had a significant positive effect on youth homicide
      for those aged 13-17 and 18-24. Such positive effects have been found for adults
      in national and neighbourhood level studies, but this is the first study to
      report such evidence for teenagers and young adults. An important policy
      implication of these findings is that the reduction of the density of retail
      alcohol outlets in a city may be an effective tool for violent crime reduction
      among such youth.

PMID- 21896074
TI  - Alcohol outlet density and harm: comparing the impacts on violence and chronic
      harms.
AB  - INTRODUCTION AND AIMS: A number of studies have previously identified
      relationships between the density of alcohol outlets and rates of violence, with
      different types of outlets related to violence in different locations. The
      previous work in Australia has been limited to studies based on police data,
      which are subject to numerous biases. This study extends the previous work by
      utilising hospital admissions as a less biased outcome measure, incorporating a
      14 year longitudinal design and by developing comparative models for violence and
      rates of alcohol use disorders. DESIGN AND METHODS: The study examines trends in
      postcode-level hospital admission data for assault and for alcohol use disorders
      over a 14 year period (n = 186) and their relationship with the density of three
      kinds of alcohol outlets. Fixed-effects models are developed to control for the
      differences between postcodes and for the overall trends in outlet density and
      morbidity rates. RESULTS: The results of this study suggest that the density of
      alcohol outlets where the main activity is alcohol consumption (i.e. pubs) is
      positively related to rates of assault-related hospital admissions, while the
      density of off-premise alcohol outlets is related to the rate of alcohol use
      disorders. DISCUSSION AND CONCLUSIONS: These findings have significant
      implications for alcohol policies in Victoria, in particular pointing to the
      significant contribution of packaged alcohol outlets to both acute and chronic
      alcohol-related harm.

PMID- 21896075
TI  - Revealing the link between licensed outlets and violence: counting venues versus
      measuring alcohol availability.
AB  - INTRODUCTION AND AIMS: Associations between alcohol-related harms and numbers of
      outlets at the neighbourhood level have been demonstrated; however, the degree to
      which alcohol consumption or sales plays a part in levels of violence is not
      clear. This has contributed to uncertainty regarding the actual mechanisms by
      which outlet density may influence levels of violence. This ecological cross
      sectional study investigated the effect of outlet numbers and alcohol sales on
      the risk of assault in Western Australia. DESIGN AND METHODS: For 2000/2001,
      information on type, number and wholesale alcohol purchases of all licensed
      outlets in operation, police-reported assault offences, socioeconomic/demographic
      data were obtained from official sources. Multivariate negative binomial
      regression was applied to at local government area level in order to assess
      associations between outlet density, alcohol sales and violence occurring in both
      licensed and domestic settings. RESULTS: Average alcohol sales volume per off
      site outlet was significantly associated with all measures of assault. Numbers of
      on-site outlets significantly predicted violence with the exception of assaults
      occurring at residential premises. Alcohol sales from off-site outlets predicted
      violence occurring at on-site outlets. DISCUSSION AND CONCLUSIONS: The link
      between on-site outlets and violence may be primarily underpinned by negative
      amenity effects while off-site outlet effects occur via increased availability.
      Alcohol sales volumes from off-site outlets influence levels of violence, which
      occur at both licensed and residential settings. The substantial and wide-ranging
      effects of liquor stores on alcohol-related harms may have been underestimated in
      the literature and by policy makers.

PMID- 21896076
TI  - Getting drunk safely? Night-life policy in the UK and its public health
      consequences.
AB  - ISSUES: Pubs, bars and nightclubs are central features of recreational night-life
      in the towns and cities of many countries. The last two decades have seen UK
      towns and cities regenerated through the provision of night-life environments
      aimed at servicing youth-focused monocultures typified by heavy drinking, loud
      music and dancing. Such changes in night-life settings have created major
      problems with management of alcohol-related violence. APPROACH: We examine what
      policies and interventions have been implemented to reduce violence in public
      night-life environments. We critically appraise the outcomes of such measures and
      whether they simply create environments in which it appears 'safe' for people to
      routinely get drunk while displacing violence and adding to health and social
      problems elsewhere. KEY FINDINGS/IMPLICATIONS: A variety of initiatives have been
      put in place to reduce violence and alcohol-related harm in night-time
      environments. These include changes to licensing laws, high profile policing,
      late night transport security, street lighting and closed circuit television
      camera networks. In some circumstances, the evidence for their effectiveness in
      containing night-life violence is relatively good. However, such approaches can
      also reduce incentives to stay sober, potentially act as a mechanism for
      displacing violence into surrounding areas, and divert public monies to city
      centre drinking environments at the expense of services in local communities.
      CONCLUSION: We argue that a public health approach to night-life is required
      which addresses drunkenness rather than pandering to the economic benefits of
      excessive alcohol use and managing any violence that is on public display.

PMID- 21896077
TI  - Do community interventions targeting licensed venues reduce alcohol-related
      emergency department presentations?
AB  - INTRODUCTION AND AIMS: Excessive alcohol consumption is related to substantial
      health and social order costs. Many of the harms have been identified as coming
      from licensed venues. Most communities struggle to find interventions that are
      effective, particularly in an environment of little federal government action.
      Furthermore, most interventions are based on little or no empirical evidence.
      This study aims to investigate the effect of a suite of interventions on
      emergency department (ED) attendances in Geelong, Australia. DESIGN AND METHODS:
      This paper reports stage one findings from the Dealing with Alcohol-Related
      Problems in the Night-time Economy project (DANTE) and specifically examines all
      alcohol-related injury frequencies before to after intervention in the City of
      Greater Geelong of Victoria, Australia, from 2005 to 2009. Auto-regressive
      integrated moving average time-series were used to determine the effect of the
      interventions on ED attendances in Geelong. RESULTS: There were 3934 triage
      presentations involving alcohol. Over two-thirds (68.9%) of triage presentations
      were male and over half (58.5%) of alcohol-related attendances occurred on the
      weekend. The time-series analyses indicated that ID scanners (z = 2.66, P <
      0.001) and the Just Think awareness campaign (z = 4.21, P < 0.001) were
      significant predictors of increases in alcohol-related injury presentation rates
      to the ED. DISCUSSION AND CONCLUSIONS: Overall, the community interventions
      implemented have not been associated with reduced alcohol-related attendances at
      the ED. The findings raise questions about whether targeting the night-time
      economy is effective and whether interventions should instead be targeted at
      reducing whole-of-community alcohol consumption.

PMID- 21896078
TI  - Behavioural indicators of motives for barroom aggression: implications for
      preventing bar violence.
AB  - INTRODUCTION AND AIMS: To develop new strategies for preventing violence in high
      risk licensed premises, we identify behavioural indicators of apparent motives
      for aggression in these settings and outline the implications of different
      motivations for prevention. DESIGN AND METHODS: The four types of motives for
      aggressive or coercive acts defined by the theory of coercive actions framed the
      research: gaining compliance, expressing grievances/restoring justice, attaining
      a favourable social identity and pursuing fun/excitement. Incidents of aggression
      from the Safer Bars evaluation research were analysed to identify behavioural
      indicators of each motivation. RESULTS: Compliance-motivated aggression typically
      takes the form of unwanted social overtures, third party intervention to stop
      conflicts or staff rule enforcement. Prevention strategies include keeping the
      aggressor's focus on compliance to avoid provoking grievance and identity motives
      that are likely to escalate aggression. Grievance motives are typically elicited
      by perceived wrongdoing and therefore prevention should focus on eliminating
      sources of grievances and adopting policies/practices to resolve grievances
      peacefully. Social identity motives are endemic to many drinking establishments
      especially among male patrons and staff. Prevention involves reducing identity
      cues in the environment, hiring staff who do not have identity concerns, and
      training staff to avoid provoking identity concerns. Aggression motivated by
      fun/excitement often involves low-level aggression where escalation can be
      prevented by avoiding grievances and attacks on identity. DISCUSSION AND
      CONCLUSIONS: Knowledge of behavioural indicators of motives can be used to
      enhance staff hiring and training practices, reduce environmental triggers for
      aggression, and develop policies to reduce motivation for aggression.

PMID- 21896080
TI  - Diagnosis of Helicobacter pylori Infection.
AB  - When an endoscopy is performed, it now becomes easier to observe indirect
      evidence of the presence of a Helicobacter pylori infection, given the progress
      of new methods including magnifying narrow band imaging or confocal laser
      endomicroscopy. Out of the biopsy-based tests, the novel original method proposed
      concerned culture in a broth medium with or without antibiotics and ELISA
      detection of H. pylori. New stool antigen tests are still appearing with no major
      improvement in comparison with the monoclonal-based tests already on the market.
      The combination of pepsinogen detection to H. pylori serology is now more and
      more evaluated to detect preneoplastic lesions.

PMID- 21896079
TI  - Epidemiology of Helicobacter pylori infection and public health implications.
AB  - This review summarizes studies on the epidemiology and public health implications
      of Helicobacter pylori published in peer-reviewed journals from April 2010
      through March 2011. Prevalence rates vary widely between different geographical
      regions and ethnic groups. An interesting study from the USA identified the
      degree of African ancestry as an independent predictor of H. pylori infection.
      Two studies have demonstrated early childhood as the period of transmission of
      infection and identified an infected sibling as an important risk factor. An oral
      oral route of spread has been substantiated with several studies showing the
      presence of H. pylori in the oral cavity. Studies have shown the presence of H.
      pylori in drinking water and the role of poor living conditions and sanitation in
      H. pylori infection, supporting an oral-fecal route of spread. Screening for H.
      pylori as a gastric cancer pre-screening strategy has been described in Japan,
      and the importance of H. pylori eradication as a gastric cancer-prevention
      strategy has now been further emphasized in Japanese guidelines. Two studies have
      shown a decrease in the burden of dyspepsia and peptic ulcer disease with H.
      pylori eradication.

PMID- 21896081
TI  - Pathogenesis of Helicobacter pylori infection.
AB  - Helicobacter pylori infections and clinical outcome are dependent on
      sophisticated interactions between the bacteria and its host. Crucial bacterial
      factors associated with pathogenicity comprise a type IV secretion system encoded
      by the cag pathogenicity island, the effector protein CagA, the vacuolating
      cytotoxin (VacA), peptidoglycan, lipopolysaccharide (LPS), gamma-glutamyl
      transpeptidase (GGT), protease HtrA, and the adhesins BabA, SabA, and others. The
      high number of these factors and allelic variation of the involved genes
      generates a highly complex scenario and reveals the difficulties in testing the
      contribution of each individual factor. Much effort has been put into identifying
      the molecular mechanisms associated with H. pylori-associated pathogenesis using
      human primary tissues, Mongolian gerbils, transgenic, knockout, and other mice as
      well as in vitro cell model systems. Interactions between bacterial factors and
      host signal transduction pathways seem to be critical for mediating the induction
      of pathogenic downstream processes and disease development. In this review
      article, we discuss the most recent progress in this research field.

PMID- 21896082
TI  - Inflammation, immunity, and vaccine development for Helicobacter pylori.
AB  - The immune response to Helicobacter pylori entails both innate effectors and a
      complex mix of Th1, Th17, and Treg adaptive immune responses. The clinical
      outcome of infection may well depend to a large degree on the relative balance of
      these responses. Vaccination with a wide range of antigens, adjuvants, and
      delivery routes can produce statistically significant reductions in H. pylori
      colonization levels in mice, though rarely sterilizing immunity. Whether similar
      reductions in bacterial load can be achieved in humans, and whether they would be
      clinically significant, is still unclear. However, progress in understanding the
      role of Th1, Th17, and most recently Treg cells in protection against H. pylori
      infection provides reason for optimism.

PMID- 21896083
TI  - Helicobacter pylori and nonmalignant diseases.
AB  - Research published over the past year has documented the continued decline of
      Helicobacter pylori-related peptic ulcer disease and increased recognition of non
      H. pylori, non-steroidal anti-inflammatory drugs ulcer disease--idiopathic
      ulcers. Despite reduced prevalence of uncomplicated PUD, rates of ulcer
      complications and associated mortality remain stubbornly high. The role of H.
      pylori in functional dyspepsia is unclear, with some authors considering H.
      pylori-associated nonulcer dyspepsia a distinct organic entity. There is
      increasing acceptance of an inverse relationship between H. pylori and
      gastroesophageal reflux disease (GERD), but little understanding of how GERD
      might be more common/severe in H. pylori-negative subjects. Research has focused
      on factors such as different H. pylori phenotypes, weight gain after H. pylori
      eradication, and effects on hormones such as ghrelin that control appetite.

PMID- 21896084
TI  - Gastric cancer: basic aspects.
AB  - Gastric cancer (GC) is a world health burden, ranging as the second cause of
      cancer death worldwide. Etiologically, GC arises not only from the combined
      effects of environmental factors and susceptible genetic variants but also from
      the accumulation of genetic and epigenetic alterations. In the last years,
      molecular oncobiology studies brought to light a number of genes that are
      implicated in gastric carcinogenesis. This review is intended to focus on the
      recently described basic aspects that play key roles in the process of gastric
      carcinogenesis. Genetic variants of the genes IL-10, IL-17, MUC1, MUC6, DNMT3B,
      SMAD4, and SERPINE1 have been reported to modify the risk of developing GC.
      Several genes have been newly associated with gastric carcinogenesis, both
      through oncogenic activation (GSK3beta, CD133, DSC2, P-Cadherin, CDH17, CD168,
      CD44, metalloproteinases MMP7 and MMP11, and a subset of miRNAs) and through
      tumor suppressor gene inactivation mechanisms (TFF1, PDX1, BCL2L10, XRCC, psiTPTE
      HERV, HAI-2, GRIK2, and RUNX3). It also addressed the role of the inflammatory
      mediator cyclooxygenase-2 (COX-2) in the process of gastric carcinogenesis and
      its importance as a potential molecular target for therapy.

PMID- 21896085
TI  - Gastric cancer: clinical aspects, epidemiology and molecular background.
AB  - The validity and usefulness of the 7th edition of the UICC tumor node metastasis
      classification in the context of clinical management of gastric cancer are
      discussed. The most relevant new agent in gastric cancer therapy is trastuzumab
      for HER2-positive gastric carcinomas. This marks the success of continuous effort
      of translational research. Trastuzumab, initially applied in palliative settings,
      is currently being evaluated also in neoadjuvant treatment regimens. Several new
      meta-analyses support the carcinogenic effect of high salt intake and smoking in
      the context of Helicobacter pylori infection. Further data have become available
      on the efficacy of protective agents, acetyl salicylic acid/nonsteroidal anti
      inflammatory drugs, and antioxidants. In search for a successful prevention
      strategy, the focus is on the identification of individuals at high risk who
      demand screening (testing) and surveillance. Serological assessment of gastric
      mucosal abnormalities with increased risk for gastric cancer development is
      extensively studied, and new data are presented from Asia as well as from Europe.
      New high-throughput techniques combined with bioinformatic vector analysis open
      the gate to the identification of new potential diagnostic and therapeutic
      targets. Furthermore, these approaches allow us to elucidate the interplay of
      bacterial virulence factors and the host's immune response as well as H. pylori
      associated alterations of mucosal gene expression.

PMID- 21896086
TI  - Treatment of Helicobacter pylori infection 2011.
AB  - This article reviews the literature published pertaining to Helicobacter pylori
      eradication over the last year. The general perception among clinicians and
      academics engaged in research on H. pylori has been that eradication rates for
      first-line therapies are falling, although some data published this year have
      cast doubt on this. The studies published this year have therefore focussed on
      developing alternative strategies for the first-line eradication of H. pylori. In
      this regard, clear evidence now exists that both levofloxacin and bismuth are
      viable options for first-line therapy. The sequential and "concomitant" regimes
      have also been studied in new settings and may have a role in future algorithms
      also. In addition, data have emerged that the probiotic Saccharomyces boulardii
      may be a useful adjunct to antibiotic therapy. Other studies promote
      individualized therapies based on host polymorphisms, age, and other such
      demographic factors.

PMID- 21896087
TI  - Helicobacter pylori in pediatrics.
AB  - This article reviewed the important publications on Helicobacter pylori research
      with children between April 2010 and March 2011. The most interesting studies in
      the last year lend further weight to the evidence for vertical transmission of H.
      pylori. The discovery of a potential role for jhp0562, the gene which encodes for
      the cell envelope protein glycosyltransferase, in the progression to peptic ulcer
      disease is also very interesting as it may provide a novel way to distinguish
      children at risk of peptic ulcer disease from those who are not, and so determine
      those who requires treatment to eradicate H. pylori. The rise in non-H. pylori
      associated ulcers and erosions continues to be reported with no apparent risk
      factors for these ulcers identified to date. High levels of treatment failure
      continue to be reported, and there remains an urgent need for more effective
      treatment regimes for children.

PMID- 21896088
TI  - Extragastric manifestations of Helicobacter pylori infection.
AB  - In the previous year, some extragastric diseases, possibly linked to Helicobacter
      pylori infection, have been largely investigated. There are, in fact, several
      studies concerning cardiovascular diseases, lung diseases, hematologic diseases,
      eye and skin diseases, hepatobiliary diseases, diabetes mellitus, and
      neurological disorders. Among them, the relationship between bacterial CagA
      positivity and coronary heart disease is reportedly emphasized. Concerning normal
      tension glaucoma, new interesting data are playing in favor of the association
      with H. pylori infection. For other diseases, there are many interesting results,
      although more studies are needed to clarify the reality of the proposed
      association.

PMID- 21896089
TI  - The other Helicobacters.
AB  - The last year has seen an interesting and important collection of evidence
      presented in the field of the "other" than Helicobacter pylori Helicobacters.
      Associations with adult ulcerative colitis and biliary/hepatic disease have been
      described. New insights into the immune response and subsequent pathogenesis
      associated with infection have also been published. Genomic advances include
      description of new and unique species and the complete genome description for
      both Helicobacter felis and Helicobacter suis. Molecular studies have also
      elucidated the mechanism of action of some functional components of these
      organisms.

PMID- 21896091
TI  - Unwanted souvenirs: travel and multi-resistant bacteria.

PMID- 21896092
TI  - Colonization of returning travelers with CTX-M-producing Escherichia coli.
AB  - BACKGROUND: We previously identified foreign travel as a risk factor for
      acquiring infections due to CTX-M (active on cefotaxime first isolated in Munich)
      producing Escherichia coli. The objective of this study was to assess the
      prevalence of extended-spectrum beta-lactamase (ESBL)-producing E coli among
      stool samples submitted from travelers as compared to non-travelers (a non
      traveler had not been outside of Canada for at least 6 months before submitting a
      stool specimen). METHODS: Once a travel case was identified, the next stool from
      a non-traveler (not been outside of Canada for at least 6 months) was included
      and cultured on the chromID-ESBL selection media. Molecular characterization was
      done using polymerase chain reaction and sequencing for bla(CTX-Ms), bla(TEMs),
      bla(SHVs), plasmid-mediated quinolone-resistant determinants, O25-ST131,
      phylogenetic groups, pulsed-field gel electrophoresis (PFGE), and multilocus
      sequencing typing. RESULTS: A total of 226 individuals were included; 195 (86%)
      were negative, and 31 (14%) were positive for ESBL-producing E coli. Notably,
      travelers were 5.2 (95% CI 2.1-31.1) times more likely than non-travelers to have
      an ESBL-producing E coli cultured from their stool. The highest rates of ESBL
      positivity were associated with travel to Africa or the Indian subcontinent.
      Among the 31 ESBL-producing E coli isolated, 22 produced CTX-M-15, 8 produced CTX
      M-14, 1 produced CTX-M-8, 12 were positive for aac(6')-Ib-cr, and 8 belonged to
      clone ST131. CONCLUSIONS: Our study confirms that foreign travel, especially to
      the Indian subcontinent and Africa, represents a major risk for rectal
      colonization with CTX-M-producing E coli and contributed to the Worldwide spread
      of these bacteria.

PMID- 21896093
TI  - Epidemiologic and biogeographic analysis of 542 VFR traveling children in
      Catalonia (Spain). A rising new population with specific needs.
AB  - BACKGROUND: Imported diseases recorded in the European Union (EU) increasingly
      involve traveling immigrants returning from visits to their relatives and friends
      (VFR). Children of these immigrant families can represent a population of extreme
      vulnerability. METHODS: A randomized cross-sectional study of 698 traveling
      children under the age of 15 was performed. VFR traveling children and non-VFR
      (or tourist) children groups were compared. RESULTS: A total of 698 individuals
      were analyzed: 354 males (50.7%) and 344 females (49.3%), with a median age
      (interquartile range) of 4 (2-9) years. Of these, 578 (82.8%) had been born in
      the EU with 542 (77.7%) being considered as VFR, whereas 156 (22.3%) were
      considered tourists. VFR children were younger (4.7 vs 8.2 yr; p < 0.001), they
      had more frequently been born in the EU (62.8% vs 20.1%; p < 0.01) and were more
      frequently lodged in private homes (76.6% vs 3.2%: p < 0.001) and rural areas
      (23.2% vs 1.6%; p < 0.001). Furthermore, VFR remained abroad longer (51.6 vs 16.6
      d; p < 0.001), the visit/travel time interval was shorter (21.8 vs 32.2 d; p <
      0.001) than tourists, and consultation was within 10 days prior to the departure
      (26.4% vs 2.7%; p < 0.001). The risk factor most differentiating VFR children
      from tourists was accommodation in a rural setting [odds ratio(OR) = 5.26;95%CI =
      2.704-10.262;p < 0.001]. CONCLUSIONS: VFR traveling children showed a greater
      risk of exposure to infectious diseases compared with tourists. Immigrant
      families may represent a target group to prioritize international preventive
      activities.

PMID- 21896094
TI  - Knowledge, attitudes, and practice of travelers' diarrhea management among
      frontline providers.
AB  - BACKGROUND: Many studies have found acute gastrointestinal infections to be among
      the most likely reason for clinic visits among forward deployed soldiers and are
      considered a significant contributor to morbidity in this population. This occurs
      despite the controlled food and water distribution systems under which military
      populations operate. Furthermore, recent studies have indicated that providers
      often fail to appropriately identify and treat the typical causes of these
      infections. To adequately address this issue, an assessment of gaps in knowledge,
      practice, and management of acute diarrhea in deployed troops was conducted.
      METHODS: A multiple-choice survey was developed by clinical researchers with
      expertise in travelers' diarrhea (TD) and provided to a convenience sample of
      clinical providers with a broad range of training and operational experience. The
      survey evaluated provider's knowledge of TD along with their ability to identify
      etiologies of various syndromic categories of acute gastrointestinal infections.
      Providers were also queried on selection of treatment approaches to a variety of
      clinical-based scenarios. RESULTS: A total of 117 respondents completed the
      survey. Most were aware of the standard definition of TD (77%); however, their
      knowledge about the epidemiology was lower, with less than 24% correctly
      answering questions on etiology of diarrhea, and 31% believing that a viral
      pathogen was the primary cause of watery diarrhea during deployment. Evaluation
      of scenario-based responses showed that 64% of providers chose not to use
      antibiotics to treat moderate TD. Furthermore, 19% of providers felt that severe
      inflammatory diarrhea was best treated with hydration only while 25% felt
      hydration was the therapy of choice for dysentery. Across all provider types,
      three practitioner characteristics appeared to be related to better scores on
      responses to the nine management scenarios: having a Doctor of Medicine or Doctor
      of Osteopathy degree, greater knowledge of TD epidemiology, and favorable
      attitudes toward antimotility or antibiotic therapy. CONCLUSION: Results from
      this survey support the need for improving knowledge and management of TD among
      deploying providers. The information from this study should be considered to
      support the establishment and dissemination of military diarrhea-management
      guidelines to assist in improving the health of military personnel.

PMID- 21896095
TI  - Symptoms of infectious diseases in immunocompromised travelers: a prospective
      study with matched controls.
AB  - BACKGROUND: Immunocompromised travelers to developing countries are thought to
      have symptomatic infectious diseases more often and longer than non
      immunocompromised travelers. Evidence for this is lacking. This study evaluates
      whether immunocompromised short-term travelers are at increased risk of diseases.
      METHODS: A prospective study was performed between October 2003 and May 2010
      among adult travelers using immunosuppressive agents (ISA) and travelers with
      inflammatory bowel disease (IBD), with their non-immunocompromised travel
      companions serving as matched controls with comparable exposure to infection.
      Data on symptoms of infectious diseases were recorded by using a structured
      diary. RESULTS: Among 75 ISA, the incidence of travel-related diarrhea was 0.76
      per person-month, and the number of symptomatic days 1.32 per month. For their 75
      controls, figures were 0.66 and 1.50, respectively (p > 0.05). Among 71 IBD, the
      incidence was 1.19, and the number of symptomatic days was 2.48. For their 71
      controls, figures were 0.73 and 1.31, respectively (p > 0.05). These differences
      also existed before travel. ISA had significantly more and longer travel-related
      signs of skin infection and IBD suffered more and longer from vomiting. As for
      other symptoms, no significant travel-related differences were found. Only 21% of
      immunocompromised travelers suffering from diarrhea used their stand-by
      antibiotics. CONCLUSIONS: ISA and IBD did not have symptomatic infectious
      diseases more often or longer than non-immunocompromised travelers, except for
      signs of travel-related skin infection among ISA. Routine prescription of stand
      by antibiotics for these immunocompromised travelers to areas with good health
      facilities is probably not more useful than for healthy travelers.

PMID- 21896096
TI  - The immunogenicity of a modified intradermal pre-exposure rabies vaccination
      schedule--a case series of 420 travelers.
AB  - BACKGROUND: Current Australian recommendations for rabies pre-exposure
      vaccination involve the use of cell-culture-based rabies vaccines, which are
      administered via intramuscular (IM) or intradermal (ID) routes. ID vaccination is
      more affordable for travelers, but is only recommended if there is sufficient
      time to perform serology 2 to 3 weeks post-vaccination and confirm immunity prior
      to travel. We report the immunogenicity of a modified ID schedule that can be
      completed in less time than the standard ID schedule, and allow more travelers to
      be vaccinated prior to departure. METHODS: Travelers were offered a modified
      schedule if they were unable to afford standard IM vaccinations, and did not have
      time to complete a standard ID course. The modified schedule consisted of two ID
      injections of 0.1 mL of human diploid cell rabies vaccine administered on days 0
      and 7, and serology was performed to determine immune status at a time between
      day 21 and 28. RESULTS: A total of 420 travelers aged between 10 and 65 years
      were vaccinated using the modified ID course. The overall seroconversion rate was
      94.5%, with 397 travelers developing antibody levels of >0.5 IU/mL when tested at
      approximately 21 days post-vaccination. CONCLUSION: The modified ID schedule used
      in this case series was highly effective, had similar immunogenicity to the
      standard ID schedule, and should be considered in travelers who are unable to
      complete standard IM or standard ID courses of rabies vaccines.

PMID- 21896097
TI  - A randomized, double-blind, pilot study of rifaximin 550 mg versus placebo in the
      prevention of travelers' diarrhea in Mexico during the dry season.
AB  - BACKGROUND: Rifaximin has been shown to be effective in treating and preventing
      travelers' diarrhea (TD) during the summer season. METHODS: The goal of this
      double-blinded multicenter trial was to assess the efficacy and safety of
      rifaximin 550 mg administered once daily for 14 days compared with placebo in the
      prevention of TD during the dry season in Mexico. RESULTS: There were 101
      participants randomized. Overall, 25 participants developed TD during the 3 weeks
      of the study: 22% from the rifaximin group and 29% from the placebo group (p =
      0.4). Mild diarrhea (defined as only one or two unformed stools during a 24-h
      period plus at least one abdominal symptoms) developed in only 3 (6%)
      participants taking rifaximin compared with 10 (21%) taking placebo during the
      first week of study (p = 0.03). No clinically significant or serious adverse
      events were reported. CONCLUSIONS: Antibiotic prophylaxis of TD in Mexico during
      the dry season needs to be further studied and its benefits weighed against the
      benefits of self-treatment.

PMID- 21896098
TI  - Acute mountain sickness in travelers who consulted a pre-travel clinic.
AB  - BACKGROUND: The main objective of this study was to investigate the incidence and
      predictors of acute mountain sickness (AMS) in travelers who consulted a pre
      travel clinic and the compliance with advices concerning this condition. METHODS:
      A post-travel questionnaire was sent to clients of five travel clinics who
      planned to climb above 2,000 m. RESULTS: The response was 77% and the data of all
      744 respondents who stayed above 2,500 m were used for the analysis. Eighty-seven
      percent (646) read and understood the written advices on AMS. The incidence of
      AMS was 25% (184), and the predictors were previous AMS [odds ratio (OR) 2.2],
      female sex (OR 1.6), age (OR 0.98 per year), maximum sleeping altitude (OR 1.2
      per 500 m), and the number of nights between 1,500 and 2,500 m (OR 0.9 per
      night). Eighty-seven percent of respondents understood the written advices about
      AMS but 21% did not read or understand the use of acetazolamide. Forty percent
      spent less than two nights between 1,500 and 2,500 m and 43% climbed more than
      500 m/d once above 2,500 m. Acetazolamide was brought along by 541 respondents
      (72%) and 116 (16%) took it preventively. Of those with AMS 62 (34%) took
      acetazolamide treatment and 87 (47%) climbed higher despite AMS symptoms. The
      average preventive dose of acetazolamide was 250 mg/d, while the average curative
      dose was 375 mg/d. We found no relation between acetazolamide prevention and AMS
      (p = 0.540). CONCLUSIONS: The incidence of AMS in travelers who stayed above
      2,500 m was 25%. Predictors were previous AMS, female sex, age, maximum overnight
      altitude, and the number of nights between 1,500 and 2,500 m. Only half of these
      travelers followed the preventive and curative advices and 21% did not read or
      understand the use of acetazolamide. We found no preventive effect of a low dose
      of acetazolamide in this retrospective observational study.

PMID- 21896099
TI  - Risk of highly resistant bacteria importation from repatriates and travelers
      hospitalized in foreign countries: about the French recommendations to limit
      their spread.

PMID- 21896100
TI  - A multidisciplinary approach in travel medicine: the pharmacist perspective.

PMID- 21896101
TI  - Preexisting cardiovascular diseases among high-altitude mountaineers in the alps.
AB  - This survey evaluated the prevalence of cardiovascular diseases (CVD) among high
      altitude mountaineers (n = 473). The prevalence of CVD amounted to 7.4% and
      increased with age. Hypertension was the most frequent type of CVD. However, the
      recorded frequency of CVD in high-altitude mountaineers is lower compared to
      hikers and alpine skiers.

PMID- 21896102
TI  - Multidrug-resistant Acinetobacter baumannii infections in three returning
      travelers evacuated from Algeria, Thailand, and Turkey after hospitalization in
      local intensive care units.
AB  - We report three cases of returning travelers evacuated from Algeria, Thailand,
      and Turkey by aero-medical repatriation, following overseas hospitalization in
      local intensive care units for accidental injuries or medical problems. All three
      patients presented with imipenem-resistant Acinetobacter baumannii infections.
      One died whereas two recovered.

PMID- 21896103
TI  - Malaria is an important differential diagnosis in visitors returning from Sri
      Lankan National Safari Parks.
AB  - Diagnostic confusion may occur between dengue and malaria when febrile patients
      with thrombocytopenia return from travel to previous malaria endemic areas.
      Laboratory tests should include blood smear examination for malaria parasites
      even though current malaria endemicity in Sri Lanka is low.

PMID- 21896104
TI  - Prevention of pediatric malaria in Japan.

PMID- 21896107
TI  - 'Telling stories about ourselves': historical methodology and the creation of
      mental health nursing narratives.
AB  - This paper considers the processes through which historical narratives are
      shaped. Interest in this area emerged from the author's struggle to understand
      contemporary mental health nursing in Ireland, and to situate this profession
      within its historical context and trajectory. It is argued that both the
      historical narrative and contemporary image of Irish mental health nursing are
      heavily influenced by the methodologies adopted by historians working in this
      area. The 'progressive historical approach', which remains the predominant
      methodological tradition adopted in nursing history, is firstly considered in
      this paper. The limitations of this approach are explored and an 'interpretive
      historical approach' is suggested as methodological counterpoint to the
      progressive tradition. 'Critical perspectives' are also considered and
      contextualized with reference to interpretive schools of thought. It is proposed
      that a fusion of the interpretive and critical approaches can offer a sound
      theoretical basis for the development of contemporary histories of nursing that
      transcends progressive narratives of altruistic caring interventions.

PMID- 21896108
TI  - Examination of the personalities and anxiety levels of children in prison: a
      sample of crime in Mugla, Turkey.
AB  - Child crime and their feelings of guilt have special importance because of their
      impact on children's development and future life. In the last few years, the
      number of young and child criminals has increased in Turkey. The sample for this
      study is from Dugerek prison in Mugla, one of the cities of the Aegean region of
      Turkey, from 18 February 2007 to 22 February 2007. The sampling group was
      randomly chosen and consisted of 41 boys aged 15-18 from the child section of the
      prison. There were no girls in that section. After a one-to-one oral interview
      with the children, a questionnaire containing the Cornell Index, Inertial Anxiety
      Inventory and demographic questions was administered. There was a highly
      positive, meaningful relationship (r: 0.771, P < 0.05) between state anxiety and
      trait anxiety levels. Our recommendation is that juvenile delinquents need more
      psychological support than their peers with normal lives, so in order to
      rehabilitate them, the number of the psychologists should be increased in this
      prison.

PMID- 21896109
TI  - Clinical differences between immigrants voluntarily and involuntarily admitted to
      acute psychiatric units: a 3-year prospective study.
AB  - Involuntary psychiatric admissions are widespread among patients with an
      immigrant background. According to a study in Norway, involuntary admissions are
      about 75% of admissions among immigrants compared to roughly 50% among ethnic
      Norwegians. The aim of the present study was to compare clinical and demographic
      characteristics of immigrant patients with involuntary or voluntary admissions to
      two acute psychiatric units. A 3-year prospective study of 94 immigrant patients
      involuntarily and voluntarily admitted to acute psychiatric units was carried
      out. Sixty-two patients (66.0%) were voluntarily and 30 (31.9%) involuntarily
      admitted. Involuntary admissions were significantly higher among men (22, 73.3%)
      compared to women (8, 26.7%; chi(2) = 4.507, d.f. = 1, P= 0.03). The mean length
      of stay for voluntary and involuntary patients were 7.8 (SD = 6.6) and 21.6 (SD =
      27.3; t=-2.7, d.f. = 88, P= 0.01). Patients diagnosed with schizophrenia and
      psychotic disorder were more often admitted involuntarily (63.0%; chi(2) = 17.83,
      P= 0.001). This study confirms that immigrant patients diagnosed with psychotic
      disorders are more often involuntarily than voluntarily admitted. Comparing the
      clinical and demographic characteristics of immigrants helps identify the reasons
      behind involuntary admissions and might improve efforts towards reducing such
      admissions in the future.

PMID- 21896110
TI  - Delivering a basic mental health training programme: views and experiences of
      Mental Health First Aid instructors in Wales.
AB  - Originating in Australia, 'Mental Health First Aid' (MHFA) is a way of providing
      support to someone who is experiencing a mental health problem before
      professional help is obtained. Positive evaluations have shown that it both
      increases confidence while decreasing stigmatizing attitudes. However, the
      evidence base surrounding the delivery of basic mental health programmes remains
      underdeveloped. This descriptive qualitative study explored the views and
      experiences of 14 MHFA instructors from across Wales through semi-structured
      interviews, as a means to identify the experience of course delivery from their
      perspective. Data were collected between January and April 2009. The study found
      individuals benefited from being an MHFA instructor through increased confidence
      and self-development. However, instructors encountered logistical difficulties in
      course delivery and noted that as attendees related to the course material, they
      wished to discuss their own mental health problems during the course. This
      created considerable challenges for instructors, who noted both positive and
      negative impacts on themselves, and on their expectations of the role of becoming
      MHFA instructors. In conclusion, basic mental health training courses must build
      a clear infrastructure, ongoing quality assurance processes and reliable support
      structures to train, support and monitor those delivering them.

PMID- 21896111
TI  - Mothers with mental illness experiencing homelessness: a critical analysis.
AB  - The experiences of homeless mothers with mental illness were examined from the
      critical perspective of feminist intersectionality. The purpose of this study was
      to unveil experiences of oppression and resistance in the lives of homeless
      mothers with mental illness, while learning from them what is conducive to their
      health. A qualitative secondary analysis was done using focus group transcripts
      from a study examining issues related to diversity and homelessness for
      psychiatric survivors and a study on mental health and housing. A purposive
      sample of 7 focus groups comprised of 67 participants was used for this study.
      Findings revealed three overarching themes: (1) discrimination based on
      intersecting social identities; (2) being stuck: the cycle of oppression; and (3)
      we're not giving up: resistance through perseverance. The contextual influences
      of mothering while homeless with a mental illness were emphasized in the results.
      The findings illuminate the need for increased on ongoing advocacy at individual
      and structural levels.

PMID- 21896112
TI  - Reflections on the education and training of mental health staff who work with
      women who have been sexually abused in childhood.
AB  - Strategies to reduce sexual assault on women patients in mental health inpatient
      acute wards have included effective policies, a consistent approach to recording
      and monitoring data relating to incidences of sexual assault, increased staff
      levels and improvements in the ward layout. A series of workshops were devised to
      enable mental health staff to work with greater awareness and sensitivity to keep
      women patients safer on inpatient wards. What emerged in particular during the
      training was the ways in which staff felt at loss as to how to build therapeutic
      relationships with women patients, particularly those with histories of sexual
      abuse. These patients may repeat early ways of relating which may at times be a
      challenge for the staff caring for them. This paper suggests that psychoanalytic
      insights offer an understanding of these ways of relating. This can be combined
      with frequent and supportive supervision to enable staff to safely articulate
      their often troubling responses to caring for women patients, this creating a
      caring and supportive environment for staff.

PMID- 21896113
TI  - A role for mental health nursing in the physical health care of consumers with
      severe mental illness.
AB  - There is extensive international evidence that people with severe mental illness
      have a lower standard of physical health than the general population. This leads
      to higher morbidity and mortality rates. Many of the causes for this poor
      physical health are modifiable. Yet the physical needs of this consumer group are
      neglected by healthcare systems in Australia, and elsewhere. While medical
      specialists are clearly integral to remedying this, nurses are well placed to
      play a key role in focused prevention and early intervention in the physical well
      being of consumers with mental health problems. This paper outlines the specifics
      on how mental health nurses can be sensitized, prepared and empowered to help
      turn this serious health issue around. In particular, mental health nurses could
      be trained in and then utilize a new physical health check and response system in
      the UK (called the Health Improvement Profile) if adapted for use within
      Australia. This profile will be briefly introduced, and then its value to
      improving health care discussed.

PMID- 21896114
TI  - An analysis of discourses shaping mental health practitioners.
AB  - A mental health practitioner (MHP) role was introduced to health services in
      southern England in 2003. The paper will discuss the initial phase within a
      longitudinal research study. A discursive approach will be adopted in order to
      understand how healthcare discourses constrain and provide possibilities for the
      emergence of a new worker role in mental health. The manner in which MHPs
      understand and talk about their work is socially constructed in interaction and
      constantly being modified by competing discourses. This paper will analyse three
      overarching health discourses, namely, the biomedical, person-centred and
      psychological discourses that have shaped MHP trainees. Discourses intersect to
      inform the role, where practices of nursing, psychology, medicine and
      occupational therapy are combined. Thus, the inclusion of physical, psychological
      and person-centred components of care serve as a multifaceted approach to care.
      This form of interprofessionalism leads MHPs one step closer in the advance
      towards an interdisciplinary discourse of holistic care.

PMID- 21896115
TI  - Educating healthcare professionals to act on the physical health needs of people
      with serious mental illness: a systematic search for evidence.
AB  - Healthcare professionals in primary and secondary care should monitor the
      physical health of people with serious mental illness, yet in practice this does
      not appear to be a routine intervention. Our objective is to develop evidence
      based training for healthcare professionals to enable them all to offer better
      physical care to this population. We performed a systematic search with the aim
      of evaluating the current evidence of the efficacy of education interventions.
      Search terms covered Severe Mental Illness, Physical Health and Education. The
      search yielded 147 papers, of which none were eligible for inclusion. A number of
      studies were excluded from this review as although there was an implicit
      education package provided to healthcare professionals, no information was
      reported on the outcomes of this education with regard to healthcare
      professionals' knowledge, attitudes and behaviours. The only information that
      these studies provided was patient-specific outcomes. It is vital that
      researchers start to publish details of healthcare professional education and
      their outcomes in physical health and serious mental illness research.

PMID- 21896116
TI  - Parenting styles and eating disorders.
AB  - The aim of the study was to analyse the parental bonding profiles in patients
      with eating disorders (ED), as well as the relationship among the different
      styles of parenting and some psychological and psychopathological variables. In
      addition, the association between the perceived parental bonding and different
      coping strategies was analysed. Perception of parenting styles was analysed in a
      sample of 70 ED patients. The Parental Bonding Instrument, Self-Esteem Scale of
      Rosenberg, Coping Strategies Inventory, State-Trait Anxiety Inventory, Beck
      Depression Inventory and Eating Disorders Inventory-2 were used. Kruskal-Wallis
      test (comparisons), Spearman correlation coefficients (association among
      different variables) and chi(2)-test (parental bonding profiles differences) were
      applied. The stereotyped style among ED patients is low care-high control during
      the first 16 years, and the same can be said about current styles of the mothers.
      Between 8.6% and 12.9% of the patients perceive their parents' styles as
      neglectful. The neglectful parenting is the style mainly involved in the specific
      ED symptoms as drive for thinness, body dissatisfaction and bulimia. In order to
      achieve a better balanced parents' role during the treatment, it would be
      necessary to improve the role of the mothers as caregivers, decreasing their role
      mainly based on the overprotection.

PMID- 21896117
TI  - Beliefs and attitudes of final-year nursing students on honour crimes: a cross
      sectional study.
AB  - The purpose of this study was to evaluate perceptions of nursing students about
      honour crimes and examine their beliefs about inquiring information from the
      victims of honour crimes. A questionnaire including demographic data was
      administered to a sample of 225 male and female final-year students in a nursing
      school. Among them, we found that significantly more male students than female
      students justify honour crimes. Although the majority of both male and female
      nursing students believed that asking for honour crimes is useful, significantly
      more male than female nursing students were against screening for honour crimes.
      This study supports the belief that gender has an influence on nurses'
      perceptions, attitudes and tolerance of honour crimes.

PMID- 21896118
TI  - Quality of Life Enjoyment and Satisfaction Questionnaire-short form for quality
      of life assessments in clinical practice: a psychometric study.
AB  - The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and its
      short form (Q-LES-Q-SF) are among the most frequently used outcome measures in
      psychiatry research. The aim of this study was to analyse the measurement
      properties of the Q-LES-Q-SF for quality of life assessments in the clinical
      settings. Fifty-seven adults with a psychiatric diagnosis participated.
      Psychometric evaluation included descriptive analysis, internal consistency, test
      retest reliability, validity, sensitivity and responsiveness analysis. The amount
      of missing data was 5.3%, while no floor or ceiling effects were observed. The
      internal consistency and test-retest coefficients were 0.9 and 0.93,
      respectfully. Almost all items significantly correlated to the total score and
      other measures used in the study, with the correlations ranging 0.41-0.81.
      Finally, the responsiveness parameters indicated the Q-LES-Q-SF is 80% sensitive
      and 100% specific measure. This preliminary analysis of the Q-LES-Q-SF
      demonstrated that it could produce reliable and valid clinical assessments of
      quality of life.

PMID- 21896119
TI  - Making an impact: The International Journal of Mental Health Nursing with a
      bullet.

PMID- 21896120
TI  - Mental health reform in Qatar.

PMID- 21896121
TI  - Placing physical activity in mental health care: a leadership role for mental
      health nurses.
AB  - The wide-ranging benefits of physical activity for consumers with mental illness
      are acknowledged within the mental health nursing field; however, this is not
      commonly translated to practice. The primary aim of this paper is to argue that
      mental health nurses are well positioned to, and should, provide leadership in
      promoting physical activity to improve the quality of care for people with mental
      illness. Topics addressed in this paper include the relationship between physical
      activity and both physical and mental health, the views and experiences of
      consumers with physical activity, the efficacy of physical activity
      interventions, the attitudes of nurses to physical activity as a component of
      care, barriers to a physical activity focus in care for mental illness, and the
      role of mental health nurses in promoting physical activity. There is a clear and
      important relationship between physical activity and mental health. Mental health
      nurses are well positioned to encourage and assist consumers to engage in
      physical activity, although they might lack the educational preparation to
      perform this role effectively.

PMID- 21896122
TI  - Myth of mental health nursing and the challenge of recovery.
AB  - Although the concept of 'mental health nursing' has grown in popularity over the
      past 35 years, it remains a myth. People believe that they know what it is and
      value it highly, but cannot describe or define it other than in vague terms. This
      paper briefly charts the rise of 'mental health nursing', emphasizing its
      political implications, and in particular, the drive towards an embrace of a
      person-centred, recovery-focused approach to care. If nurses are to realize such
      ambitions, they must resolve their historical association with psychiatric
      nursing. The concept of the 'mental health nurse' might signal the emergence of a
      new vision for human services, but might also signal the need for 'mental health
      nurses' to negotiate a formal separation from the traditional 'psychiatric'
      family.

PMID- 21896124
TI  - Phentermine therapy for obesity does not elevate blood pressure.

PMID- 21896125
TI  - Genetic mosaicism and Fitzpatrick skin type.

PMID- 21896126
TI  - Is cosmetic platelet-rich plasma a drug to be regulated by the Food and Drug
      Administration?
AB  - In the area of cosmetic dermatology, some physicians have been injecting
      activated platelet-rich plasma into the face to promote cosmesis or using it to
      enhance fat grafts. However, subtle changes to the federal drug code (21 CFR
      1271.1) made in 2004, when applied to activated PRP, purport to make this
      autologous substance a federally regulated drug requiring an extensive and costly
      Biologics License Application. Are autologous cells drugs? Many physicians
      believe there are significant problems with this regulatory paradigm.

PMID- 21896127
TI  - Randomized trial comparing a chemical peel containing a lipophilic hydroxy acid
      derivative of salicylic acid with a salicylic acid peel in subjects with
      comedonal acne.
AB  - BACKGROUND: Lipohydroxyacid is a lipophilic derivative of salicylic acid with
      comedolytic properties. OBJECTIVES: To compare lipohydroxyacid and salicylic acid
      peels in subjects with comedonal acne. METHODS: In this split face, randomized
      study, 20 subjects with comedonal acne received lipohydroxyacid peels on one side
      of the face, while the other side was treated with salicylic acid peels. A total
      of six peels at 2-week intervals were performed. Efficacy was evaluated by
      counting noninflammatory and inflammatory lesions and by performing a global
      change in acne assessment. Safety was assessed by evaluating adverse events,
      global tolerance, and the presence of erythema, scaling, and dryness. RESULTS:
      There was a statistically significant decrease of 55.6% and 48.5% from baseline
      to Day 98 in the mean number of noninflammatory lesions for the sides treated
      with lipohydroxyacid and salicylic acid peels, respectively (P < 0.001). There
      was no significant difference in the degree of reduction in noninflammatory
      lesions between the two peels. There was no significant reduction in the number
      of inflammatory lesions. Both peels were generally very well tolerated.
      CONCLUSION: This study suggests that lipohydroxyacid peels can be beneficial to
      subjects with comedonal acne.

PMID- 21896128
TI  - Enhanced delivery of cosmeceuticals by microdermabrasion.
AB  - BACKGROUND: Microdermabrasion (MDA) is one of the top five nonsurgical cosmetic
      procedures performed. It is a well-established technology with widespread
      applications in the cosmetic industry. AIMS: To investigate the effects of MDA on
      skin and delivery of cosmeceuticals. METHODS: The alternation of skin structure
      post-MDA was examined by histological sectioning and transepidermal water loss
      measurements. The effect of MDA treatment on skin permeation profiles of
      hydrophilic and lipophilic molecules was investigated by laser scanning confocal
      microscopy and in vitro permeation studies. RESULTS: Confocal images indicated
      different absorption profiles and permeation depths for hydrophilic and
      lipophilic molecules. Microdermabrasion enhanced the transdermal delivery of
      nicotinamide, the model hydrophilic compound employed. On the other hand,
      permeation of retinol, the model lipophilic compound, did not improve after
      treatment with MDA. When treated with 20 passes, the skin recovered from MDA
      induced changes in 4 days. CONCLUSION: Permeation of cosmeceuticals into skin was
      found to be affected by their lipophilicity. Application of skin care products
      post-MDA therapy may be promising to improve their dermal uptake.

PMID- 21896129
TI  - A clinical evaluation of the comparable efficacy of hyaluronic acid-based foam
      and ceramide-containing emulsion cream in the treatment of mild-to-moderate
      atopic dermatitis.
AB  - BACKGROUND: A variety of prescription devices have been developed to improve
      barrier function in persons with atopic dermatitis. These products are based
      primarily on the use of occlusive agents to decrease transepidermal water loss,
      creating an environment for optimal healing. AIM: A newly developed hyaluronic
      acid based, pH neutral foam technology formulated to maximize humectancy and
      normalize transepidermal waster loss was evaluated for its ability to optimize
      barrier function while minimizing unnecessary irritation. METHODS: This double
      blind split body study enrolled 20 subjects with mild to moderate symmetrical
      atopic dermatitis involving body surface area greater than or equal to 10% using
      the arms or the legs as the target site. Subjects were randomized to apply the
      hyaluronic acid based emollient foam or the reference ceramide-containing
      emulsion cream to one side of the body with the other test product applied to the
      opposite side. Subject and investigator ratings were made for erythema, scaling,
      lichenification, excoriation, itching, stinging, and burning at baseline, week 2,
      and week 4. RESULTS: Both formulations achieved statistically significant
      improvement in all clinical signs and symptoms of atopic dermatitis by week 4,
      however the hyaluronic acid foam achieved statistically significant improvement
      in overall eczema severity by week 2, whereas the ceramide-containing emulsion
      cream did not. The subject's preference statistically significantly favored the
      foam in terms of ability to spread, moisturize, ease of use, and lack of odor. In
      addition, the foam was preferred for effectiveness and ability to soothe.
      CONCLUSION: A prescription hyaluronic acid based foam device offers an aesthetic
      formulation with excellent efficacy in patients requiring an environment for
      barrier repair with mild to moderate atopic dermatitis.

PMID- 21896130
TI  - Efficacy of a novel hydroquinone-free skin-brightening cream in patients with
      melasma.
AB  - BACKGROUND: For treating irregular skin pigmentation, a hallmark of premature
      skin aging, safe and effective alternatives to hydroquinone and kojic acid are
      being researched. AIMS: Four skin-brightening actives targeting melanin formation
      at multiple levels, namely disodium glycerophosphate, L-leucine, phenylethyl
      resorcinol, and undecylenoyl phenylalanine, in an oil-in-water emulsion cream
      were evaluated. PATIENTS/METHODS: Twenty female patients with mild-to-moderate
      epidermal melasma were included. After a washout period of 1 month with a
      sunscreen, they continued using the sunscreen and added the novel skin
      brightening cream for 12 weeks twice daily to entire face. RESULTS: Whereas there
      was no significant change in skin pigmentation during the washout, signs for
      uneven skin tone including melasma area and severity and appearance of lentigines
      significantly decreased by up to 43% after the 12-week treatment period with the
      skin-brightening cream. The skin-brightening complex is well tolerated, which
      should allow its continued use over a prolonged period of time, in particular,
      when comparing skin-brightening approaches with exfoliating or peeling agents.
      CONCLUSIONS: When used with a daily sunscreen, the skin-brightening complex
      represents a valuable alternative to hydroquinone products and can be used for
      maintenance or adjunct skin care with lightening therapies.

PMID- 21896131
TI  - Patient knowledge and attitudes on laser hair removal: a survey in people of
      color.
AB  - BACKGROUND: It is now widely accepted that dark-complexioned skin individuals can
      be safely treated with laser hair removal (LHR). However, some people are still
      concerned about the side effects or have been told that hair removal laser is not
      possible in darkly pigmented skin. AIMS: To measure the knowledge and attitudes
      of African Americans about LHR and assess the need for additional education
      focusing on LHR. PATIENTS/METHODS: A cross-sectional survey with questionnaire
      was administered to African American subjects between the ages of 21-70 years.
      Questions comprised attitudes and knowledge about LHR. Demographic
      characteristics, attitudes, and knowledge were assessed by descriptive
      statistics. Results were considered statistically significant if P <0.05.
      RESULTS: The survey was completed by 221 African American subjects. There were
      only 122 subjects (55.2%) who knew that dark-skinned individuals can be treated
      with LHR. Only 44.3% of subjects believed that dark-skinned people are more prone
      to develop hyperpigmentation from LHR. Female subjects and subjects with higher
      educational background have a higher tendency to consider LHR as a treatment
      choice (P < 0.05). CONCLUSIONS: This study shows that many African Americans
      still have negative attitudes and lack knowledge about LHR. The results of this
      study provide information that can lead to better informed dermatology providers
      who can then better educate patients of color regarding LHR knowledge.

PMID- 21896132
TI  - A 10% glycolic acid containing oil-in-water emulsion improves mild acne: a
      randomized double-blind placebo-controlled trial.
AB  - BACKGROUND: Acne is characterized by hyperseborrhea, follicular hyperkeratosis,
      and growth of propionibacteria. Alpha hydroxy acids depending on the pH of the
      finished product exhibit comedolytic as well as antimicrobial properties.
      OBJECTIVES: The aim of this study was to investigate an oil-in-water emulsion
      containing 10% glycolic acid (pH 4; Dr. August Wolff GmbH & Co. KG Arzneimittel,
      Bielefeld, Germany) as monotherapy in mild acne regarding clinical efficacy and
      tolerability for 90 days. PATIENTS AND METHODS: Patients (n = 120; 73 f, 47 m)
      suffering from mild acne (Leeds score 0.25-1) aged >=12 (mean 21 +/- 5.8) were
      included in this double-blind, placebo-controlled, randomized, monocentric trial.
      The cream was applied once daily in the evening. No additional products were
      used. Cleansing was standardized by supplying the same product to all patients.
      RESULTS: The number of patients (n = 115) in the per-protocol and intention-to
      treat analysis was the same. Acne improved significantly in the verum group up to
      day 90. Already at day 45, there was a statistical significant (5% level)
      difference against placebo. The subjective evaluation of the verum by physicians
      and patients regarding clinical efficacy and tolerability was favorable.
      Regarding reported adverse effects, there was no statistically significant
      difference (5% level) between verum and placebo. CONCLUSIONS: The 10% glycolic
      acid containing oil-in-water emulsion improved mild acne applied as monotherapy
      in this study significantly, already after 45 days of treatment. Regarding
      tolerability, there was no objective or subjective difference between the 10%
      glycolic acid containing oil-in-water emulsion and the corresponding placebo.

PMID- 21896133
TI  - A study of fractional CO2 laser resurfacing: the best fluences through a
      clinical, histological, and ultrastructural evaluation.
AB  - BACKGROUND: Fractional resurfacing is a laser treatment modality to create
      numerous microscopic thermal injury zones of controlled width, depth, and density
      that are surrounded by a reservoir of spared epidermal and dermal tissue,
      allowing rapid repair of laser-induced thermal injury. OBJECTIVE: To evaluate the
      safety and efficacy of a fractional CO(2) laser system in the treatment of photo
      damaged skin with clinical, histological, and ultrastructural evaluation, with
      special attention to one of the parameters of this laser system: the fluences.
      MATERIALS AND METHODS: Twelve patients with Fitzpatrick skin types II to III with
      photo-damage skin underwent fractional laser treatment with one single-pass
      superficial on the face and forearm. Clinical outcome and histological and
      ultrastructural changes were assessed. RESULTS: Light microscopy of biopsies gave
      important information about skin changes at three different times after
      fractional treatment, especially revealing some differences between the fluences
      used in the three groups of patients. CONCLUSION: Fractional resurfacing offers
      significant surgical advantages allowing to achieve excellent esthetic results in
      balance with the biological structure. Besides, our study shows already that with
      2.07 and 2.77 J/cm(2) , instead of 4.15 J/cm(2) , it is possible to reach a
      biological response without scar formation.

PMID- 21896134
TI  - Facial skin-lightening benefits of the tetrapeptide Pro-Lys-Glu-Lys on subjects
      with skin types V-VI living in South Africa.
AB  - BACKGROUND: Irregular skin pigmentation may be a substantial contributor to the
      signs of aging and to a person's lack of psychological well-being. Although a
      large number of skin-lightening agents are available, the opportunity exists to
      identify more efficacious agents, agents that target alternative biological
      mechanisms. AIMS: To provide clinical evidence of the skin-lightening effect of
      the tetrapeptide, Pro-Lys-Glu-Lys (PKEK), on subjects with skin types V-VI living
      in South Africa. METHODS: Pro-Lys-Glu-Lys was evaluated in a double-blind and
      vehicle-controlled clinical study using expert grading of digital images by
      comparing its effects in subjects with skin types V-VI suffering from facial
      melasma and postinflammatory hyperpigmentation. RESULTS: This study demonstrated
      the efficacy of PKEK on subjects with skin types V-VI. On comparing the two
      treatments, the skin-lightening peptide-containing formulation was significantly
      superior to the vehicle at 12 weeks on overall appearance (P < 0.05) and evenness
      of skin tone (P < 0.01). CONCLUSIONS: The tetrapeptide, PKEK, has proven skin
      lightening benefits on skin discoloration from melasma and postinflammatory
      hyperpigmentation. These studies have been conducted on subjects with skin types
      V-VI living in South Africa, but we believe this technology to be suitable for
      all racial groups.

PMID- 21896135
TI  - Extensive necrosis after injection of hyaluronic acid filler: case report and
      review of the literature.
AB  - BACKGROUND: Use of dermal fillers for soft tissue augmentation has become an
      integral part of aesthetic practices. Dermal fillers temporarily remove the
      appearance of rhytids and reduce the depth of skin folds. Even with the most
      experienced of injectors, adverse effects can and do occur ranging from mild
      bruising to severe injection necrosis. AIMS: Physicians should be able to treat
      the severe complication of vascular necrosis and detect impending necrosis after
      injection of a dermal filler, especially with hyaluronic acid fillers. MATERIALS
      AND METHODS: Case report of a patient who was followed for 6 months from time of
      injection of hyaluronic acid filler to complete healing of wound. RESULTS:
      Complete wound healing was achieved with early recognition and institution of
      treatment. DISCUSSION: We review a case report of injection necrosis and methods
      used to prevent and treat this complication. CONCLUSION: Early recognition of
      vascular necrosis with specific protocol for treatment after injection necrosis
      with hyaluronic acid fillers improves the outcome of wound healing.

PMID- 21896136
TI  - Safety and efficacy of administering abobotulinumtoxinA through a single
      injection point when treating lateral periocular rhytides.
AB  - A retrospective analysis was performed to assess efficacy and patient
      satisfaction associated with AbobotulinumtoxinA for the treatment of dynamic
      periocular rhytides. When keeping the total dose of ABA the same for each side of
      the face, one injection point yielded the same efficacy and safety as three
      separate injection points into the lateral periocular areas.

PMID- 21896137
TI  - Nodular skin reactions in eyebrow permanent makeup: two case reports and an
      infection by Mycobacterium haemophilum.
AB  - BACKGROUND: Permanent makeup is becoming more and more popular. The procedures,
      however, bear some medical risks. AIMS: We will describe possible adverse effects
      of the procedure. METHODS: This is a report of clinical observations. RESULTS: We
      report about two women aged 26 and 47 years, who developed nodules with some
      delay after permanent tattooing the eyebrows. Clinical, histologic, and
      laboratory investigations revealed a noninfectious granulomatous reaction not
      responding to topical calcineurin inhibitor but corticosteroids in the younger
      patient. In the other woman, an infection by Mycobacterium haemophilum could be
      identified. A triple combination of clarithromycin, ciprofloxacin, and rifampicin
      succeeded in clearance of the lesions. CONCLUSIONS: Adverse reactions after
      permanent makeup need a medical evaluation to identify health risks and initiate
      early treatment.

PMID- 21896138
TI  - Decrease in glutathione may be involved in pathogenesis of acne vulgaris.
AB  - BACKGROUND: Some past studies reported that oxidative stress components such as
      reactive oxygen species (ROS) or lipid peroxide (LPO) are involved in the
      pathogenesis and progression of acne vulgaris. In this study, we hypothesized
      that the pathogenesis of acne vulgaris may depend on the differences in
      antioxidative activity among antioxidants in our body. We collected samples of
      stratum corneum from acne patients and healthy subjects and compared the quantity
      of gluthathione (GSH), one of many antioxidative components in our body, for
      comparison. METHODS: Samples of stratum corneum were collected from facial acne
      involved lesion, facial uninvolved area, and the medial side of the upper arm in
      acne vulgaris patients. Similarly, samples were collected from a facial
      uninvolved area and the medial side of the upper arm in healthy subjects. The
      quantity of GSH was measured in each area. In vitro effects of alpha-melanocyte
      stimulating hormone (alpha-MSH) on GSH synthesis-related gene were also examined.
      RESULTS: The quantity of GSH in stratum corneum from each area was significantly
      lower in acne vulgaris patients than that of healthy subjects. There was no
      significant difference in quantity of GSH between the acne-involved lesion and
      uninvolved area in acne patients. In vitro studies showed that the expression
      level of Glutamate-cysteine ligase catalytic subunit (GCLC), one of the GSH
      synthesis-related genes, was significantly decreased by the additional use of
      alpha-MSH. CONCLUSIONS: We conclude that a decline in antioxidative activity led
      by a decrease in GSH quantity may play an important role in pathogenesis of acne
      vulgaris. The use of alpha-MSH may further decrease the GSH level.

PMID- 21896139
TI  - The impact of topical photoprotectants intended for daily use on lifetime
      ultraviolet exposure.
AB  - BACKGROUND: Exposure to solar ultraviolet (UV) radiation is believed to be an
      important contributor to facial photoaging. Daily application of topical
      photoprotectants is thought to mitigate this process. OBJECTIVES: To examine the
      importance of a number of independent factors in reducing the lifetime UV
      exposure of facial skin achieved by daily use of photoprotective products.
      METHODS: A behavioral model of solar UV exposure to the face is incorporated with
      the spectral profile of two different candidate topical products, the age at
      which regular photoprotection begins, the SPF of the products, and whether the
      product is applied year-round or just in the summer months to examine the
      reduction in lifetime UV exposures achieved by daily use of photoprotective
      products. RESULTS: The results show that regular use of topical photoprotective
      agents reduces significantly lifetime UV exposure to the face compared with
      nonuse. Analysis of variance shows that the most important factor is to begin
      regular daily use early in life. The SPF and spectral profile of the product is
      of lesser importance, as is whether daily use is confined to the summer months
      rather than year-round. CONCLUSIONS: While it remains unproven and speculative,
      there is good reason to suppose that regular use of daily facial topical products
      containing UV filters, particularly if started early in adult life, will be
      translated into fewer visible signs of aging later in life.

PMID- 21896141
TI  - A compendium of antihypertensive therapy.

PMID- 21896142
TI  - Thiazide and loop diuretics.
AB  - KEY POINTS AND PRACTICAL RECOMMENDATIONS: *  Although chlorthalidone and
      hydrochlorothiazide are structurally similar, they are very different
      pharmacokinetically, with chlorthalidone having both an extremely long half-life
      (approximately 40 to 60 hours) and a large volume of distribution, with gradual
      elimination from the plasma compartment by tubular secretion. *  Furosemide
      usage, the most widely used diuretic in the loop diuretic class, can be
      complicated by extremely erratic absorption, with a bioavailability range of 12%
      to 112%. *  Chlorthalidone, at a dose of 25 mg, is comparatively more potent than
      50 mg of hydrochlorothiazide, particularly as related to overnight blood pressure
      reduction. *  In ALLHAT, there was no difference among chlorthalidone,
      amlodipine, lisinopril, and doxazosin for the primary outcome or mortality. * 
      Secondary outcomes were similar except for a 38% higher rate of heart failure
      with amlodipine; a 10% higher rate of combined cardiovascular disease, a 15%
      higher rate of stroke, and a 19% higher rate of heart failure with lisinopril;
      and a 20% higher rate of cardiovascular disease, a 20% higher rate of stroke (40%
      higher rate in blacks), and an 80% higher rate of heart failure with doxazosin,
      compared with chlorthalidone. *  The ACCOMPLISH study may affect future practice
      guidelines as a result of its findings favoring the amlodipine/benazepril
      combination; however, the generalizability to patient populations with a lesser
      cardiovascular risk profile remains in question and the dose of
      hydrochlorothiazide was only 12.5 mg to 25 mg daily, which was a dose lower than
      that used in placebo-controlled trials using hydrochlorothiazide. *  Certain low
      renin patient groups (eg, blacks, the elderly, and diabetics) as well as those
      who manifest the metabolic syndrome are commonly more responsive to thiazide-type
      diuretic therapy. *  Diuretics can be successfully combined with beta-blockers,
      angiotensin-converting enzyme inhibitors, angiotensin receptor blockers,
      centrally acting agents, and even calcium channel blockers. *  Although thiazide
      type diuretics are among the best-tolerated antihypertensive agents in terms of
      symptomatic adverse effects, diuretic-related adverse side effects include those
      with established mechanisms (eg, such as electrolyte changes and/or metabolic
      abnormalities) and other side effects, which are less well understood
      mechanistically (eg, impotence), although the latter is not universally accepted
      as a diuretic-related side effect. *  Thiazide-induced hypokalemia is associated
      with increased blood glucose, and treatment of thiazide-induced hypokalemia may
      reverse glucose intolerance and possibly prevent diabetes. *  Thiazide-induced
      hyperuricemia occurs as a result of volume contraction and competition with uric
      acid for renal tubular secretion, but does not necessarily contraindicate using a
      thiazide, especially if a uric acid-lowering drug such as allopurinol is being
      used. *  Adverse interactions include the blunting of thiazide effects by
      nonsteroidal anti-inflammatory drugs and the potential to increase fatigue,
      lethargy, and increase in glucose when combined with beta-blockers. *  Thiazide
      type diuretics are useful first-line agents in the treatment of hypertension
      because they have been proven to reduce cardiovascular mortality and morbidity in
      systolic and diastolic forms of hypertension and do so at low cost. *  Loop
      diuretics should not be used as first-line therapy in hypertension since there
      are no outcome data with them. They should be reserved for conditions of
      clinically significant fluid overload (eg, heart failure and significant fluid
      retention with vasodilator drugs, such as minoxidil) or with advanced renal
      failure and can be combined with thiazide-type diuretics.

PMID- 21896143
TI  - Aldosterone blockers (mineralocorticoid receptor antagonism) and potassium
      sparing diuretics.
AB  - KEY POINTS AND PRACTICAL RECOMMENDATIONS: *  Mineralocorticoid receptor (MR)
      antagonists (aldosterone blockers) provide effective antihypertensive treatment,
      especially in low-renin and salt-sensitive forms of hypertension, including
      resistant hypertension. *  Newer, more selective MR antagonists (eg, eplerenone)
      have fewer of the progestational and antiandrogenic effects than spironolactone,
      enhancing tolerability and potentially improving adherence to therapy. *  MR
      antagonists provide an additional benefit in the treatment of heart failure when
      combined with angiotensin-converting enzyme inhibitors, digoxin, and loop
      diuretics. *  Other potassium-sparing diuretics (amiloride or triamterene) are
      generally prescribed for essential hypertension as a fixed-dose combination with
      hydrochlorothiazide. *  The dose range for spironolactone with resistant
      hypertension is between 25 mg/d and 50 mg/d, and eplerenone is an appropriate
      alternative if spironolactone is not tolerated because of sexual side effects. * 
      In general, the combined use of spironolactone and adequate doses of a thiazide
      diuretic or a thiazide-like agent such as chlorthalidone for the treatment of
      resistant hypertension maximizes efficacy and reduces the risk of spironolactone
      induced hyperkalemia.

PMID- 21896144
TI  - beta-Adrenergic blockers.
AB  - KEY POINTS AND PRACTICAL RECOMMENDATIONS: *  beta-Blockers are appropriate
      treatment for patients with hypertension and those who have concomitant ischemic
      heart disease, heart failure, obstructive cardiomyopathy, or certain arrhythmias.
      *  beta-Blockers can be used in combination with other antihypertensive drugs to
      achieve maximal blood pressure control. Labetalol can be used in hypertensive
      emergencies and urgencies. *  beta-Blockers may be useful in patients having
      hyperkinetic circulation (palpitations, tachycardia, hypertension, and anxiety),
      migraine headache, and essential tremor. *  beta-Blockers are highly
      heterogeneous with respect to various pharmacologic effects: degree of intrinsic
      sympathomimetic activity, membrane-stabilizing activity, beta(1) selectivity,
      alpha(1) -adrenergic-blocking effect, tissue solubility, routes of systemic
      elimination, potencies and duration of action, and specific effects may be
      important in the selection of a drug for clinical use. *  beta-Blocker usage to
      reduce perioperative ischemia and cardiovascular complications may not benefit as
      many patients as was once hoped and may actually cause harm in some individuals.
      Currently the best evidence supports beta-blocker use in two patient groups:
      patients undergoing vascular surgery with known ischemic heart disease or
      multiple risk factors for it and for patients already receiving beta-blockers for
      known cardiovascular conditions.

PMID- 21896145
TI  - Alpha 1 adrenoreceptor antagonists.
AB  - KEY POINTS AND PRACTICAL RECOMMENDATIONS: *  alpha Antagonists lower blood
      pressure by selectively blocking post-synaptic alpha(1) -adrenoreceptors, which
      antagonizes catecholamine-induced constriction of the arterial and venous
      vascular beds. *  alpha(1) -Adrenoreceptor antagonists are not indicated for
      initial, first-line antihypertensive therapy; however, they can be added to most
      other antihypertensive drug classes in--preferably diuretic-containing--drug
      regimens. *  When used over time, these agents cause expansion of the
      extracellular fluid and plasma volumes that typically manifests as weight gain
      and an attenuation of the blood pressure-lowering efficacy in persons who are
      consuming usual amounts of dietary sodium. *  Utilization of alpha(1) 
      adrenoreceptor antagonists with diuretics such as chlorthalidone or
      hydrochlorothiazide is beneficial because these agents minimize the alpha
      antagonist-induced expansion of the extracellular and plasma volumes while
      providing significant incremental reductions in blood pressure. *  alpha(1) 
      Adrenoreceptor antagonists are especially useful in men with benign prostatic
      hypertrophy because they increase mean and peak urinary flow rates as well as
      reduce lower urinary tract symptoms. *  alpha(1) -Adrenoreceptor antagonists are
      contraindicated in persons with heart failure because of their aforementioned
      ability to expand extracellular and plasma volumes.

PMID- 21896146
TI  - Central sympatholytic drugs.
AB  - KEY POINTS: *  Central sympatholytic drugs reduce blood pressure mainly by
      stimulating central alpha(2) -adrenergic receptors in the brainstem centers,
      thereby reducing sympathetic nerve activity and neuronal release of
      norepinephrine to the heart and peripheral circulation. *  This class of drugs,
      however, is currently used mainly as fourth-line (or beyond) drug therapy for
      hypertension because of side effects of drowsiness, fatigue, and dry mouth. * 
      Rebound hypertension is also another major concern in certain drugs with a short
      half-life, particularly in patients who are nonadherent to the regimen.
      Therefore, their use on a "PRN" basis for treatment of blood pressure surge in
      the absence of symptoms or acute target complications should also be avoided.

PMID- 21896147
TI  - Renin inhibitors.
AB  - KEY POINTS AND PRACTICAL RECOMMENDATIONS: *  Aliskiren, the sole oral renin
      inhibitor approved by the US Food and Drug Administration, is indicated for the
      treatment of hypertension, either as monotherapy or in combination, with
      reductions in blood pressure similar to other agents. *  Early evidence suggests
      that aliskiren confers additional benefit in patients with diabetic nephropathy.
      Data are not yet available to determine whether protection will extend to
      cardiovascular disease. *  No initial dosage adjustment is required in elderly
      patients or for patients with mild to severe renal impairment; however, clinical
      experience is limited in patients with significant renal impairment, and with
      renal artery stenosis. *  It appears rational to combine aliskiren with agents
      that otherwise increase plasma renin activity, including thiazide diuretics,
      angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. * 
      While there is a reactive rise in renin in response to aliskiren, probably larger
      than that induced by angiotensin receptor blockers and angiotensin-converting
      enzyme inhibitors, there is no evidence that this rise is harmful. *  In placebo
      controlled studies, the incidence of edema anywhere in the body was 0.4% with
      aliskiren compared with 0.5% with placebo. It is unknown whether angioedema rates
      are higher in blacks with aliskiren. *  Aliskiren is associated with a slight
      increase in cough, with rates of about one third to one half seen with
      angiotensin-converting enzyme inhibitors. *  Increases in serum potassium >5.5
      meq/L were infrequent in patients with essential hypertension treated with
      aliskiren alone (0.9% compared with 0.6% with placebo).

PMID- 21896148
TI  - Angiotensin-converting enzyme inhibitors.
AB  - KEY POINTS AND RECOMMENDATIONS: *  In addition to hypertension, angiotensin
      converting enzyme inhibitors are indicated for treatment of patients at high risk
      for coronary artery disease, after myocardial infarction, with dilated
      cardiomypathy, or with chronic kidney disease. *  The most familiar angiotensin
      converting enzyme subtype, angiotensin-converting enzyme-1 (kininase II), cleaves
      the vasoconstrictor octapeptide angiotensin II from its inactive decapeptide
      precursor, angiotensin I, while simultaneously inactivating the vasodilator
      bradykinin. *  Biochemical pathways within and around the renin-angiotensin
      system are highly species-specific; there is little evidence that "angiotensin
      converting enzyme bypass pathways" have major clinical implications in humans. * 
      Dietary sodium loading can diminish or abolish the antihypertensive effect of an
      angiotensin-converting enzyme inhibitor, while salt restriction or concomitant
      diuretic therapy enhances it. *  Dose-response curves with angiotensin-converting
      enzyme inhibitors are quite flat but their peak effects vary in different
      individuals. *  Increased serum creatinine (decreased glomerular filtration rate)
      during acute or chronic angiotensin-converting enzyme inhibition identifies
      individuals likely to experience long-term renal protective benefits. * 
      Angiotensin-converting enzyme inhibitors are contraindicated in pregnancy due to
      fetal toxicity. *  Use of angiotensin-converting enzymes can be limited by
      idiosyncratic reactions (cough or angioedema), hyperkalemia (usually in cardiac
      or renal failure or with combined renin-angiotensin blockade) or hypotension
      (usually with severe volume-depletion or cardiac failure).

PMID- 21896150
TI  - Angiotensin receptor blockers: pharmacology, efficacy, and safety.
AB  - KEY POINTS AND PRACTICAL RECOMMENDATIONS: *  The angiotensin receptor blockers
      are highly effective antihypertensive agents that are also particularly well
      tolerated. *  There are no major differences in efficacy or other clinical
      characteristics among older drugs in this class, although some of the newer
      agents may more effectively reduce blood pressure than older agents. *  Major
      randomized clinical trials have demonstrated that angiotensin receptor blockers
      provide significant outcomes benefits in conditions such as diabetic nephropathy,
      chronic heart failure or heart failure following myocardial infarction,
      hypertension with left ventricular hypertrophy and in patients whose histories of
      previous events or complicated diabetes puts them at high cardiovascular risk. * 
      In treating hypertension, angiotensin receptor blockers can be used as first-line
      therapy or added at later stages of treatment titration. *  These drugs are very
      effective in combination with thiazide diuretics or calcium channel blockers and
      there are several single-pill, fixed-dose combinations of angiotensin receptor
      blockers with hydrochlorothiazide, amlodipine, or aliskiren. These combinations
      can be given as initial therapy (where appropriate) or later in the course of
      treatment. Three-drug combinations (angiotensin receptor blocker plus amlodipine
      plus hydrochlorothiazide and angiotensin receptor blocker plus aliskiren plus
      hydrochlorothiazide) are also available.

PMID- 21896151
TI  - Calcium channel blockers.
AB  - KEY POINTS AND PRACTICAL RECOMMENDATIONS: *  Calcium channel blockers, which
      dilate arteries by reducing calcium flux into cells, effectively lower blood
      pressure, especially in combination with other drugs, and some formulations of
      agents of this class are approved for treating angina or cardiac dysrhythmias. * 
      Calcium channel blockers reduce blood pressure across all patient groups,
      regardless of sex, race/ethnicity, age, and dietary sodium intake. * 
      Nondihydropyridine calcium channel blockers are more negatively chronotropic and
      inotropic than the dihydropyridine subclass, which is important for patients with
      cardiac dysrhythmias or who need beta-blockers. *  Extensive experience in
      comparative randomized trials indicates that an initial calcium antagonist can
      prevent all major types of cardiovascular disease, except heart failure (for
      which a diuretic is superior). Initial dihydropyridine calcium channel blockers
      have not reduced the rate of progression of renal disease as well as inhibitors
      of the renin-angiotensin system, although members of the nondihydropyridine
      subclass can reduce albuminuria. *  High doses of dihydropyridine calcium channel
      blockers often cause edema, headache, flushing and tachycardia; high doses of
      verapamil can cause constipation. Diltiazem and verapamil have important drug
      interaction with digoxin and cyclosporine, among others.

PMID- 21896152
TI  - Direct-acting vasodilators.
AB  - KEY POINTS AND PRACTICAL RECOMMENDATIONS: *  Hydralazine and minoxidil act by
      dilating resistance arterioles, thus reducing peripheral resistance, with no
      dilating effect on the venous side of the circulation. *  There is a baroreflex
      mediated venoconstriction, resulting in an increase in venous return to the
      heart, along with a direct catecholamine-mediated positive inotropic and
      chronotropic stimulation of the heart. *  Hydralazine therapy is usually combined
      with a sympathetic inhibitor to prevent expression of this reflex, as well as
      with a diuretic agent to prevent sodium retention caused by reduction in renal
      perfusion pressure. *  Hydralazine is indicated in the long-term therapy of
      essential hypertension, in the short-term therapy of pregnancy-induced
      hypertension and eclampsia, and in the therapy of hypertensive crisis. *  Adverse
      effects include the anticipated tachycardia, fluid retention, and headache,
      caused by the vasodilation, especially in the early days of therapy, but may
      frequently be prevented by the concomitant use of a beta-blocker. *  As with
      other drugs that are N-acetylated, there is a low risk of lupus-like syndrome
      with high doses and long-term use. *  Because of the severity of adverse effects
      with minoxidil, its usage is limited to persons with severe hypertension
      unresponsive to other treatments. *  Hirsutism, a common side effect of
      minoxidil, is particularly bothersome in women and reverses in a few months after
      discontinuation. *  Sodium nitroprusside is used in the intensive care setting to
      lower pressure in hypertensive crisis or to treat severe left ventricular
      failure, particularly valuable when elevated pressure or severe left ventricular
      failure threatens the patient's survival. *  Although nitrates have not achieved
      widespread use as antihypertensive agents, they are effective in producing
      sustained blood pressure (BP) reductions when added to other antihypertensive
      regimens.

PMID- 21896153
TI  - PROGRESS: Prevention of Recurrent Stroke.
AB  - The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a
      randomized placebo-controlled trial which clearly demonstrated that perindopril
      based blood pressure (BP)-lowering treatment is one of the most effective and
      generalizable strategies for secondary prevention of stroke. Beneficial effects
      of BP lowering were observed on recurrent stroke, other cardiovascular events,
      disability, dependency, and cognitive function across a variety of subgroups
      defined by age, sex, geographical region, body mass index, diabetes, atrial
      fibrillation, chronic kidney disease, and baseline BP levels. Once patients with
      stroke have stabilized, all patients should receive BP-lowering therapy
      irrespective of their BP levels. On the basis of recommendations from current
      international guidelines, BP should be lowered to <140/90 mm Hg in all patients
      with cerebrovascular disease and to <130/80 mm Hg if therapy is well tolerated.

PMID- 21896154
TI  - Factors associated with within-herd transmission of serotype A foot-and-mouth
      disease virus in cattle, during the 2001 outbreak in Argentina: a protective
      effect of vaccination.
AB  - Argentina suffered an extensive foot-and-mouth disease (FMD) epidemic between
      July 2000 and January 2002, 3 months after obtaining the official FMD-free
      without vaccination status conferred by the World Organization for Animal Health.
      This is one of the largest FMD epidemics controlled by implementation of a
      systematic mass vaccination campaign in an FMD-free country. In 2000, 124 herds
      were reported as FMD positive, 2394 herds in 2001 and one in January 2002; the
      total number of cattle herds in the country at that time was approximately 230
      000. Estimates of FMD transmission are important to understand the dynamics of
      disease spread and for estimating the value for the parameterization of disease
      transmission models, with the ultimate goals of predicting its spread, assessing
      and designing control strategies, conducting economic analyses and supporting the
      decision-making process. In this study, the within-herd coefficient of
      transmission, beta, was computed for herds affected in the 2001 FMD epidemic and
      categorized as low or high based on the median value of beta. A logistic
      regression model was fitted to identify factors significantly associated with
      high values of beta. Results suggested that the odds of having a high within-herd
      transmission were significantly associated with time from initial herd infection
      to disease detection, date of report, vaccination, and time from initial herd
      infection to herd vaccination. Results presented in this study demonstrate, in
      quantifiable terms, the protective impact of vaccination in reducing FMD
      transmission in infected herds. These results will be useful for the
      parameterization of epidemiological models aimed at quantifying the impact of
      vaccination and for the design and implementation of FMD emergency vaccination
      strategies in face of an epidemic.

PMID- 21896155
TI  - Levels of periodontal pathogens in neonatal gastric aspirates and possible
      maternal sites of origin.
AB  - Maternal periodontal infection has been recognized as a risk factor for preterm
      and low birthweight infants. It is suspected that pathogens causing periodontal
      disease may translocate to the amniotic cavity and so contribute to triggering an
      adverse pregnancy outcome. This study aimed to determine levels and proportions
      of periodontal bacteria in neonatal gastric aspirates obtained from complicated
      pregnancies and the respective maternal oral and vaginal samples using a
      quantitative polymerase chain reaction approach, and also to determine the origin
      of the neonate's bacteria by sequence comparisons between the three sites.
      Aggregatibacter actinomycetemcomitans and Tannerella forsythia were not observed
      in the neonates or in the women's vaginas. Interestingly, Porphyromonas
      gingivalis was identified in the neonates in two samples (2.98E+02 and 1.75E+02
      cells ml(-1)) and in association with Fusobacterium nucleatum, which was observed
      at high prevalence (10%) and at high levels reaching up to 2.32E+03 cells ml(-1).
      Although F. nucleatum was also present in the vaginal samples, the results
      demonstrated that the neonatal strains were more likely to originate from the
      mother's oral cavity than to be vaginal strains.

PMID- 21896156
TI  - Clonal structure of Streptococcus sanguinis strains isolated from endocarditis
      cases and the oral cavity.
AB  - A collection of Streptococcus sanguinis strains from patients with endocarditis
      (n = 21) and from the oral cavity (n = 34) was subjected to a multi-locus
      sequence typing analysis using seven housekeeping genes, carbamoyl-phosphate
      synthetase (carB), Co/Zn/Cd efflux system component (czcD), d-alanyl-d-alanine
      ligase (ddl), DNA polymerase III (dnaX), glucose-6-phosphate dehydrogenase (gdh),
      DNA-directed RNA polymerase, beta subunit (rpoB) and superoxide dismutase (sodA).
      The scheme was expanded by the inclusion of two the putative virulence genes,
      bacitracin-resistance protein (bacA) and saliva-binding protein (ssaB), to
      increase strain discrimination. Extensive intra-species recombination was
      apparent in all genes but inter-species recombination was also apparent with
      strains apparently harbouring gdh and ddl from unidentified sources and one
      isolate harboured a sodA allele apparently derived from Streptococcus oralis. The
      recombination/mutation ratio for the concatenated housekeeping gene sequences was
      1.67 (95% confidence limits 1.25-2.72) and for the two virulence genes the r/m
      ratio was 3.99 (95% confidence limits 1.61-8.72); recombination was the major
      driver for genetic variation. All isolates were distinct and the endocarditis
      strains did not form distinct sub-clusters when the data were analysed using
      ClonalFrame. These data support the widely held opinion that infecting S.
      sanguinis strains are opportunistic human pathogens.

PMID- 21896157
TI  - Polymicrobial periodontal pathogen transcriptomes in calvarial bone and soft
      tissue.
AB  - Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia are
      consistently associated with adult periodontitis. This study sought to document
      the host transcriptome to a P. gingivalis, T. denticola, and T.forsythia
      challenge as a polymicrobial infection using a murine calvarial model of acute
      inflammation and bone resorption. Mice were infected with P. gingivalis, T.
      denticola, and T. forsythia over the calvaria, after which the soft tissues and
      calvarial bones were excised. A Murine GeneChip((r)) array analysis of transcript
      profiles showed that 6997 genes were differentially expressed in calvarial bones
      (P < 0.05) and 1544 genes were differentially transcribed in the inflamed tissues
      after the polymicrobial infection. Of these genes, 4476 and 1035 genes in the
      infected bone and tissues were differentially expressed by upregulation.
      Biological pathways significantly impacted by the polymicrobial infection in
      calvarial bone included leukocyte transendothelial migration (LTM), cell adhesion
      molecules, adherens junction, major histocompatibility complex antigen,
      extracellular matrix-receptor interaction, and antigen processing and
      presentation resulting in inflammatory/cytokine/chemokine transcripts stimulation
      in bone and soft tissue. Intense inflammation and increased activated osteoclasts
      were observed in calvarias compared with sham-infected controls. Quantitative
      real-time RT-PCR analysis confirmed that the mRNA level of selected genes
      corresponded with the microarray expression. The polymicrobial infection
      regulated several LTM and extracellular membrane pathway genes in a manner
      distinct from mono-infection with P. gingivalis, T. denticola, or T. forsythia.
      To our knowledge, this is the first definition of the polymicrobially induced
      transcriptome in calvarial bone and soft tissue in response to periodontal
      pathogens.

PMID- 21896158
TI  - Analysis of Porphyromonas gingivalis PG27 by deletion and intragenic suppressor
      mutation analyses.
AB  - PG27 is required for secretion of virulence factor gingipains, and has recently
      been proposed as LptO, which is involved in O-deacylation of lipopolysaccharide.
      In the present study, a predicted 14 anti-parallel beta-strand structure of PG27
      was ascertained. Deletion study showed that the region from Asp382 to the C
      terminal His391 of PG27 is dispensable for the function of PG27. Analysis of C
      terminal deletion mutants revealed that the region in strand S14 (Asn369-Gly385)
      is important for activity. Of the gingipain-defective mutants, DeltaThr378-His391
      and DeltaPhe377-His391 produced amounts of PG27 comparable to those produced by
      wild-type cells, suggesting that Thr378-Phe381 contains essential residues for
      the function of PG27. In contrast, DeltaPhe381-His391, DeltaAla380-His391,
      DeltaLeu379-His391 and DeltaArg376-His391 produced no detectable PG27. The
      defects of the DeltaAla380-His391 mutant were suppressed by changing either
      Ala346 or Ala359 of PG27 to valine. Importantly, Ala346 and Ala359 are located
      close to Leu379 in the structural model of PG27. A359V compensated for the
      instability of PG27, but not the gingipain-defective phenotypes, of other
      deletion mutants tested, suggesting that Ala380 and Phe381 of PG27 are important
      for the stability of PG27. Lastly, we found that the C-terminal region of PG27
      may be located in the periplasm. Taken together, these findings fit well with a
      predicted beta-barrel structure model for PG27, and show that strand S14 is
      important for its function.

PMID- 21896159
TI  - Mononuclear cell therapy attenuates atherosclerosis in apoE KO mice.
AB  - BACKGROUND: Recent studies have highlighted the potential of cell therapy for
      atherosclerosis. The aim of this study was to evaluate the effects of mononuclear
      cell (MNC) therapy on the development of atherosclerotic lesions in the
      apolipoprotein E knockout (apoE KO) mouse. METHODS: We investigated vascular
      lipid deposition, vascular remodeling, oxidative stress, and endothelial nitric
      oxide synthase (eNOS) expression in apoE KO mice treated with spleen MNCs
      isolated from lacZ transgenic mice (apoE KO-MNC) for 8 weeks compared to
      untreated control mice (apoE KO). RESULTS: Histological analysis of aortas showed
      a significant reduction in the lipid deposition area in apoE KO-MNC mice compared
      to apoE KO mice (0.051 +/- 0.004 vs 0.117 +/- 0.016 mm2, respectively, p < 0.01).
      In addition, vessel morphometry revealed that MNC therapy prevented the outward
      (positive) remodeling in apoE KO mice that is normally observed (apoE KO-MNC:
      0.98 +/- 0.07 vs apoE KO: 1.37 +/- 0.09), using wild-type mice (C57BL/6J) as a
      reference. ApoE KO-MNC mice also have reduced production of superoxide anions and
      increased eNOS expression compared to apoE KO mice. Finally, immunohistochemistry
      analysis revealed a homing of endothelial progenitor cells (EPCs) in the aortas
      of apoE KO-MNC mice. CONCLUSION: MNC therapy attenuates the progression of
      atherosclerosis in the aortas of apoE KO mice. Our data provide evidence that the
      mechanism by which this attenuation occurs includes the homing of EPCs, a
      decrease in oxidative stress and an upregulation of eNOS expression.

PMID- 21896160
TI  - Fatty acid profiles and their distribution patterns in microalgae: a
      comprehensive analysis of more than 2000 strains from the SAG culture collection.
AB  - BACKGROUND: Among the various biochemical markers, fatty acids or lipid profiles
      represent a chemically relatively inert class of compounds that is easy to
      isolate from biological material. Fatty acid (FA) profiles are considered as
      chemotaxonomic markers to define groups of various taxonomic ranks in flowering
      plants, trees and other embryophytes. RESULTS: The fatty acid profiles of 2076
      microalgal strains from the culture collection of algae of Gottingen University
      (SAG) were determined in the stationary phase. Overall 76 different fatty acids
      and 10 other lipophilic substances were identified and quantified. The obtained
      FA profiles were added into a database providing information about fatty acid
      composition. Using this database we tested whether FA profiles are suitable as
      chemotaxonomic markers. FA distribution patterns were found to reflect
      phylogenetic relationships at the level of phyla and classes. In contrast, at
      lower taxonomic levels, e.g. between closely related species and even among
      multiple isolates of the same species, FA contents may be rather variable.
      CONCLUSION: FA distribution patterns are suitable chemotaxonomic markers to
      define taxa of higher rank in algae. However, due to their extensive variation at
      the species level it is difficult to make predictions about the FA profile in a
      novel isolate.

PMID- 21896162
TI  - Semiconducting properties of layered cadmium sulphide-based hybrid
      nanocomposites.
AB  - A series of hybrid cadmium salt/cationic surfactant layered nanocomposites
      containing different concentrations of cadmium sulphide was prepared by
      exchanging chloride by sulphide ions in the layered precursor CdXx(OH)y(CnTA)z in
      a solid phase/gas reaction, resulting in a series of layered species exhibiting
      stoichiometries corresponding to CdSvXx(OH)y(CnTA)z, constituted by two
      dimensional CdCl2/CdS ultra-thin sheets sandwiched between two self-assembled
      surfactant layers. The electronic structure of CdS in the nanocomposite is
      similar to that of bulk, but showing the expected features of two-dimensional
      confinement of the semiconductor. The nanocomposite band gap is found to depend
      in a non-linear manner on both the length of the hydrocarbon chain of the
      surfactant and the concentration of the sulphide in the inorganic sheet. The
      products show photocatalytic activity at least similar and usually better than
      that of "bulk" CdS in a factor of two.

PMID- 21896161
TI  - Higher whole-blood selenium is associated with improved immune responses in
      footrot-affected sheep.
AB  - We reported previously that sheep affected with footrot (FR) have lower whole
      blood selenium (WB-Se) concentrations and that parenteral Se-supplementation in
      conjunction with routine control practices accelerates recovery from FR. The
      purpose of this follow-up study was to investigate the mechanisms by which Se
      facilitates recovery from FR. Sheep affected with FR (n = 38) were injected
      monthly for 15 months with either 5 mg Se (FR-Se) or saline (FR-Sal), whereas 19
      healthy sheep received no treatment. Adaptive immune function was evaluated after
      3 months of Se supplementation by immunizing all sheep with a novel protein,
      keyhole limpet hemocyanin (KLH). The antibody titer and delayed-type
      hypersensitivity (DTH) skin test to KLH were used to assess humoral immunity and
      cell-mediated immunity, respectively. Innate immunity was evaluated after 3
      months of Se supplementation by measuring intradermal responses to histamine 30
      min after injection compared to KLH and saline, and after 15 months of Se
      supplementation by isolating neutrophils and measuring their bacterial killing
      ability and relative abundance of mRNA for genes associated with neutrophil
      migration. Compared to healthy sheep, immune responses to a novel protein were
      suppressed in FR-affected sheep with smaller decreases in FR-affected sheep that
      received Se or had WB-Se concentrations above 250 ng/mL at the time of the immune
      assays. Neutrophil function was suppressed in FR-affected sheep, but was not
      changed by Se supplementation or WB-Se status. Sheep FR is associated with
      depressed immune responses to a novel protein, which may be partly restored by
      improving WB-Se status (> 250 ng/mL).

PMID- 21896163
TI  - How do women at increased, but unexplained, familial risk of breast cancer
      perceive and manage their risk? A qualitative interview study.
AB  - BACKGROUND: The perception of breast cancer risk held by women who have not had
      breast cancer, and who are at increased, but unexplained, familial risk of breast
      cancer is poorly described. This study aims to describe risk perception and how
      it is related to screening behaviour for these women. METHODS: Participants were
      recruited from a population-based sample (the Australian Breast Cancer Family
      Study - ABCFS). The ABCFS includes women diagnosed with breast cancer and their
      relatives. For this study, women without breast cancer with at least one first-
      or second-degree relative diagnosed with breast cancer before age 50 were
      eligible unless a BRCA1 or BRCA2 mutation had been identified in their family.
      Data collection consisted of an audio recorded, semi-structured interview on the
      topic of breast cancer risk and screening decision-making. Data was analysed
      thematically. RESULTS: A total of 24 interviews were conducted, and saturation of
      the main themes was achieved. Women were classified into one of five groups:
      don't worry about cancer risk, but do screening; concerned about cancer risk, so
      do something; concerned about cancer risk, so why don't I do anything?; cancer
      inevitable; cancer unlikely. CONCLUSIONS: The language and framework women use to
      describe their risk of breast cancer must be the starting point in attempts to
      enhance women's understanding of risk and their prevention behaviour.

PMID- 21896164
TI  - Rapid analysis of formic acid, acetic acid, and furfural in pretreated wheat
      straw hydrolysates and ethanol in a bioethanol fermentation using atmospheric
      pressure chemical ionisation mass spectrometry.
AB  - Atmospheric pressure chemical ionisation mass spectrometry (APCI-MS) offers
      advantages as a rapid analytical technique for the quantification of three
      biomass degradation products (acetic acid, formic acid and furfural) within
      pretreated wheat straw hydrolysates and the analysis of ethanol during
      fermentation. The data we obtained using APCI-MS correlated significantly with
      high-performance liquid chromatography analysis whilst offering the analyst
      minimal sample preparation and faster sample throughput.

PMID- 21896165
TI  - HCV entry receptors as potential targets for siRNA-based inhibition of HCV.
AB  - BACKGROUND: Hepatitis C virus (HCV) is a major health concern with almost 3% of
      the world's population (350 million individuals) and 10% of the Pakistani
      population chronically infected with this viral pathogen. The current therapy of
      interferon-alpha and ribavirin against HCV has limited efficiency, so alternative
      options are desperately needed. RNA interference (RNAi), which results in a
      sequence-specific degradation of HCV RNA has potential as a powerful alternative
      molecular therapeutic approach. Concerning viral entry, the HCV structural gene
      E2 is mainly involved in virus attachment to the host cell surface receptors
      i.e., CD81 tetraspanin, scavenger receptor class B type 1 (SR-B1), low density
      lipoprotein receptor (LDLR) and claudin1 (CLDN1). RESULTS: In this report, we
      studied the relationship of the HCV receptors CD81, LDL, CLDN1 and SR-B1to HCV
      infection. The potential of siRNAs to inhibit HCV-3a replication in serum
      infected Huh-7 cells was demonstrated by treatment with siRNAs against HCV
      receptors, which resulted in a significant decrease in HCV viral copy number.
      CONCLUSIONS: Our data clearly demonstrate that the RNAi-mediated silencing of HCV
      receptors is among the first of its type for the development of an effective
      siRNA-based therapeutic option against HCV-3a. These findings will shed further
      light on the possible role of receptors in inhibition of HCV-3a viral titre
      through siRNA mediated silencing.

PMID- 21896166
TI  - Mucin granule-associated proteins in human bronchial epithelial cells: the airway
      goblet cell "granulome".
AB  - BACKGROUND: Excess mucus in the airways leads to obstruction in diseases such as
      chronic bronchitis, asthma, and cystic fibrosis. Mucins, the highly glycosolated
      protein components of mucus, are stored in membrane-bound granules housed in the
      cytoplasm of airway epithelial "goblet" cells until they are secreted into the
      airway lumen via an exocytotic process. Precise mechanism(s) of mucin secretion,
      including the specific proteins involved in the process, have yet to be
      elucidated. Previously, we have shown that the Myristoylated Alanine-Rich C
      Kinase Substrate (MARCKS) protein regulates mucin secretion by orchestrating
      translocation of mucin granules from the cytosol to the plasma membrane, where
      the granules dock, fuse and release their contents into the airway lumen.
      Associated with MARCKS in this process are chaperone (Heat Shock Protein 70
      [HSP70], Cysteine string protein [CSP]) and cytoskeletal (actin, myosin)
      proteins. However, additional granule-associated proteins that may be involved in
      secretion have not yet been elucidated. METHODS: Here, we isolated mucin granules
      and granule membranes from primary cultures of well differentiated human
      bronchial epithelial cells utilizing a novel technique of immuno-isolation, based
      on the presence of the calcium activated chloride channel hCLCA1 (the human
      ortholog of murine Gob-5) on the granule membranes, and verified via Western
      blotting and co-immunoprecipitation that MARCKS, HSP70, CSP and hCLCA1 were
      present on the granule membranes and associated with each other. We then
      subjected the isolated granules/membranes to liquid chromatography mass
      spectrometry (LC-MS/MS) to identify other granule associated proteins. RESULTS: A
      number of additional cytoskeletal (e.g. Myosin Vc) and regulatory proteins (e.g.
      Protein phosphatase 4) associated with the granules and could play a role in
      secretion were discovered. This is the first description of the airway goblet
      cell "granulome."

PMID- 21896167
TI  - XMRV: usage of receptors and potential co-receptors.
AB  - BACKGROUND: XMRV is a gammaretrovirus first identified in prostate tissues of
      Prostate Cancer (PC) patients and later in the blood cells of patients with
      Chronic Fatigue Syndrome (CFS). Although XMRV is thought to use XPR1 for cell
      entry, it infects A549 cells that do not express XPR1, suggesting usage of other
      receptors or co-receptors. METHODS: To study the usage of different receptors and
      co- receptors that could play a role in XMRV infection of lymphoid cells and
      GHOST (GFP- Human osteosarcoma) cells expressing CD4 along with different
      chemokine receptors including CCR1, CCR2, etc., were infected with XMRV. Culture
      supernatants and cells were tested for XMRV replication using real time
      quantitative PCR. RESULTS: Infection and replication of XMRV was seen in a
      variety of GHOST cells, LNCaP, DU145, A549 and Caski cell lines. The levels of
      XMRV replication varied in different cell lines showing differential replication
      in different cell lines. However, replication in A549 which lacks XPR1 expression
      was relatively higher than DU145 but lower than, LNCaP. XMRV replication varied
      in GHOST cell lines expressing CD4 and each of the co- receptors CCR1-CCR8 and
      bob. There was significant replication of XMRV in CCR3 and Bonzo although it is
      much lower when compared to DU145, A549 and LNCaP. CONCLUSION: XMRV replication
      was observed in GHOST cells that express CD4 and each of the chemokine receptors
      ranging from CCR1- CCR8 and BOB suggesting that infectivity in hematopoietic
      cells could be mediated by use of these receptors.

PMID- 21896168
TI  - Prohibitin is overexpressed in Huh-7-HCV and Huh-7.5-HCV cells harboring in vitro
      transcribed full-length hepatitis C virus RNA.
AB  - BACKGROUND: Currently, up-regulated proteins and apoptosis in hepatitis C is a
      hot topic in exploring the pathogenic mechanism of Heptitis C Virus(HCV). Some
      recent studies shows that prohibitin is overexpressed in cells expressing HCV
      core proteins, and up-regulated prohibitin is also found in human hepatoma cell
      line HCC-M, lung cancer, prostate cancer, and other cancers. Prohibitin is an
      important member of the membrane protein superfamily, and it plays a role of
      molecular chaperones in mitochondrial protein stability. Meanwhile, it has a
      permissive action on tumor growth or acts as an oncosuppressor. Based on our
      previously established the in vitro HCV cell-culture system (HCVcc), here we
      aimed to investigate the different expression profiles of prohibitin in Huh-7-HCV
      and Huh-7.5-HCV cells METHODS: The total cellular RNA of Huh-7, Huh-7.5, Huh-7
      HCV and Huh-7.5-HCV cells were extracted, and then the first-strand cDNA was
      reversely transcribed. The expression of prohibitin at the mRNA level was
      assessed by real-time PCR with GAPDH as the control. Furthermore, the expression
      of prohibitin at the protein level was evaluated by western blot with GAPDH as an
      internal control. RESULTS: Our results of real-time PCR showed that the mRNA
      expression level of prohibitin in Huh-7-HCV cells was 2.09 times higher than that
      in Huh-7 cells, while, the mRNA level of prohibitin in Huh-7.5-HCV cells was 2.25
      times higher than that in Huh-7.5 cells. The results of western blot showed that
      the protein expression level of prohibitin in Huh-7-HCV cells was 2.38 times
      higher than that in Huh-7 cells, while the protein expression of prohibitin in
      Huh-7.5-HCV cells was 2.29 times higher than that in Huh-7.5 cells. CONCLUSIONS:
      The expression of prohibitin was relatively high in Huh-7-HCV and Huh-7.5-HCV
      cells harboring in vitro transcribed full-length HCV RNA.

PMID- 21896169
TI  - Progressive severe lung injury by zinc oxide nanoparticles; the role of Zn2+
      dissolution inside lysosomes.
AB  - BACKGROUND: Large production volumes of zinc oxide nanoparticles (ZnONP) might be
      anticipated to pose risks, of accidental inhalation in occupational and even in
      consumer settings. Herein, we further investigated the pathological changes
      induced by ZnONP and their possible mechanism of action. METHODS: Two doses of
      ZnONP (50 and 150 cm2/rat) were intratracheally instilled into the lungs of rats
      with assessments made at 24 h, 1 wk, and 4 wks after instillation to evaluate
      dose- and time-course responses. Assessments included bronchoalveolar lavage
      (BAL) fluid analysis, histological analysis, transmission electron microscopy,
      and IgE and IgA measurement in the serum and BAL fluid. To evaluate the
      mechanism, alternative ZnONP, ZnONP-free bronchoalveolar lavage exudate, and
      dissolved Zn2+ (92.5 MUg/rat) were also instilled to rats. Acridine orange
      staining was utilized in macrophages in culture to evaluate the lysosomal
      membrane destabilization by NP. RESULTS: ZnONP induced eosinophilia,
      proliferation of airway epithelial cells, goblet cell hyperplasia, and pulmonary
      fibrosis. Bronchocentric interstitial pulmonary fibrosis at the chronic phase was
      associated with increased myofibroblast accumulation and transforming growth
      factor-beta positivity. Serum IgE levels were up-regulated by ZnONP along with
      the eosinophilia whilst serum IgA levels were down-regulated by ZnONP. ZnONP are
      rapidly dissolved under acidic conditions (pH 4.5) whilst they remained intact
      around neutrality (pH 7.4). The instillation of dissolved Zn2+ into rat lungs
      showed similar pathologies (eg., eosinophilia, bronchocentric interstitial
      fibrosis) as were elicited by ZnONP. Lysosomal stability was decreased and cell
      death resulted following treatment of macrophages with ZnONP in vitro.
      CONCLUSIONS: We hypothesise that rapid, pH-dependent dissolution of ZnONP inside
      of phagosomes is the main cause of ZnONP-induced diverse progressive severe lung
      injuries.

PMID- 21896170
TI  - Talk, trust and time: a longitudinal study evaluating knowledge translation and
      exchange processes for research on violence against women.
AB  - BACKGROUND: Violence against women (VAW) is a major public health problem.
      Translation of VAW research to policy and practice is an area that remains
      understudied, but provides the opportunity to examine knowledge translation and
      exchange (KTE) processes in a complex, multi-stakeholder context. In a series of
      studies including two randomized trials, the McMaster University VAW Research
      Program studied one key research gap: evidence about the effectiveness of
      screening women for exposure to intimate partner violence. This project developed
      and evaluated KTE strategies to share research findings with policymakers, health
      and community service providers, and women's advocates. METHODS: A longitudinal
      cross-sectional design, applying concurrent mixed data collection methods
      (surveys, interviews, and focus groups), was used to evaluate the utility of
      specific KTE strategies, including a series of workshops and a day-long Family
      Violence Knowledge Exchange Forum, on research sharing, uptake, and use. RESULTS:
      Participants valued the opportunity to meet with researchers, provide feedback on
      key messages, and make personal connections with other stakeholders. A number of
      factors specific to the knowledge itself, stakeholders' contexts, and the nature
      of the knowledge gap being addressed influenced the uptake, sharing, and use of
      the research. The types of knowledge use changed across time, and were
      specifically related to both the types of decisions being made, and to stage of
      decision making; most reported use was conceptual or symbolic, with few examples
      of instrumental use. Participants did report actively sharing the research
      findings with their own networks. Further examination of these second-order
      knowledge-sharing processes is required, including development of appropriate
      methods and measures for its assessment. Some participants reported that they
      would not use the research evidence in their decision making when it contradicted
      professional experiences, while others used it to support apparently
      contradictory positions. The online wiki-based 'community of interest' requested
      by participants was not used. CONCLUSIONS: Mobilizing knowledge in the area of
      VAW practice and policy is complex and resource-intensive, and must acknowledge
      and respect the values of identified knowledge users, while balancing the
      objectivity of the research and researchers. This paper provides important
      lessons learned about these processes, including attending to the potential
      unintended consequences of knowledge sharing.

PMID- 21896171
TI  - Assessment of peri- and postoperative complications and Karnofsky-performance
      status in head and neck cancer patients after radiation or chemoradiation that
      underwent surgery with regional or free-flap reconstruction for salvage,
      palliation, or to improve function.
AB  - BACKGROUND: Surgery after (chemo)radiation (RCTX/RTX) is felt to be plagued with
      a high incidence of wound healing complications reported to be as high as 70%.
      The additional use of vascularized flaps may help to decrease this high rate of
      complications. Therefore, we examined within a retrospective single-institutional
      study the peri--and postoperative complications in patients who underwent surgery
      for salvage, palliation or functional rehabilitation after (chemo)radiation with
      regional and free flaps. As a second study end point the Karnofsky performance
      status (KPS) was determined preoperatively and 3 months postoperatively to assess
      the impact of such extensive procedures on the overall performance status of this
      heavily pretreated patient population. FINDINGS: 21 patients were treated between
      2005 and 2010 in a single institution (17 male, 4 female) for salvage (10/21),
      palliation (4/21), or functional rehabilitation (7/21). Overall 23 flaps were
      performed of which 8 were free flaps. Major recipient site complications were
      observed in only 4 pts. (19%) (1 postoperative haemorrhage, 1 partial flap loss,
      2 fistulas) and major donor site complications in 1 pt (wound dehiscence). Also 2
      minor donor site complications were observed. The overall complication rate was
      33%. There was no free flap loss. Assessment of pre- and postoperative KPS
      revealed improvement in 13 out of 21 patients (62%). A decline of KPS was noted
      in only one patient. CONCLUSIONS: We conclude that within this (chemo)radiated
      patient population surgical interventions for salvage, palliation or improve
      function can be safely performed once vascularised grafts are used.

PMID- 21896172
TI  - Paresthesia and forearm pain after phlebotomy due to medial antebrachial
      cutaneous nerve injury.
AB  - BACKGROUND: Although phlebotomy is a common procedure, there is limited
      information concerning to documented complications of venipuncture. CASE
      PRESENTATION: A 45 year old left- handed woman was refered for elecrodiagnostic
      study with dysesthesia and pain in left medial forearm. She noted these symptoms
      three weeks after phelebotomy. Electrodiagnostic study showed severe involvement
      of left side Medial Antebrachial Cutaneous nerve (MAC nerve). CONCLUSION:
      Phelebotomy is a cause of MAC nerve injury. Electrodiagnostic testing can be
      helpful in evaluating cases of sensory disturbance after phlebotomy.

PMID- 21896173
TI  - High prevalence of syphilis among demobilized child soldiers in Eastern Congo: a
      cross-sectional study.
AB  - BACKGROUND: Syphilis, a known major public health issue for soldiers during
      periods of conflict, is exacerbated in the Democratic Republic of Congo due to
      widespread sexual violence. However, there has been no previous study to
      determine the extent of this problem. Therefore, we determined the prevalence of
      syphilis among young demobilized soldiers. METHODS: Screening of syphilis using
      the rapid plasma reagin test and the Treponema pallidum hemagglutination assay
      was conducted in three transit sites of soldier reintegration in 2005. The Fisher
      Exact probability test was used to compare results. RESULTS: The prevalence of
      syphilis was found to be 3.4%, with almost equal distribution in respect to sex,
      location. CONCLUSION: Syphilis continues to be highly prevalent in demobilized
      child soldiers in Eastern Congo. Syphilis screening tests are recommended.

PMID- 21896174
TI  - Meniscoplasty for stable osteochondritis dissecans of the lateral femoral condyle
      combined with a discoid lateral meniscus: a case report.
AB  - INTRODUCTION: Osteochondritis dissecans of the lateral femoral condyle is
      relatively rare, and it is reported to often be combined with a discoid lateral
      meniscus. Given the potential for healing, conservative management is indicated
      for stable osteochondritis dissecans in patients who are skeletally immature.
      However, patients with osteochondritis dissecans of the lateral femoral condyle
      combined with a discoid lateral meniscus often have persistent symptoms despite
      conservative management. CASE PRESENTATION: We present the case of a seven-year
      old Korean girl who had osteochondritis dissecans of the lateral femoral condyle
      combined with a discoid lateral meniscus, which healed after meniscoplasty for
      the symptomatic lateral discoid meniscus without surgical intervention for the
      osteochondritis dissecans. In addition, healing of the osteochondritis dissecans
      lesion was confirmed by an MRI scan five months after the operation. CONCLUSIONS:
      Meniscoplasty can be recommended for symptomatic stable juvenile osteochondritis
      dissecans of the lateral femoral condyle combined with a discoid lateral meniscus
      when conservative treatment fails.

PMID- 21896175
TI  - Severe bronchopulmonary dysplasia improved by noninvasive positive pressure
      ventilation: a case report.
AB  - INTRODUCTION: This is the first report to describe the feasibility and
      effectiveness of noninvasive positive pressure ventilation in the secondary
      treatment of bronchopulmonary dysplasia. CASE PRESENTATION: A former male preterm
      of Caucasian ethnicity delivered at 29 weeks gestation developed severe
      bronchopulmonary dysplasia. At the age of six months he was in permanent
      tachypnea and dyspnea and in need of 100% oxygen with a flow of 2.0 L/minute via
      a nasal cannula. Intermittent nocturnal noninvasive positive pressure ventilation
      was then administered for seven hours daily. The ventilator was set at a positive
      end-expiratory pressure of 6 cmH2O, with pressure support of 4 cmH2O, trigger at
      1.4 mL/second, and a maximum inspiratory time of 0.7 seconds. Over the course of
      seven weeks, the patient's maximum daytime fraction of inspired oxygen via nasal
      cannula decreased from 1.0 to 0.75, his respiratory rate from 64 breaths/minute
      to 50 breaths/minute and carbon dioxide from 58 mmHg to 44 mmHg. CONCLUSION:
      Noninvasive positive pressure ventilation may be a novel therapeutic option for
      established severe bronchopulmonary dysplasia. In the case presented, noninvasive
      positive pressure ventilation achieved sustained improvement in ventilation and
      thus prepared our patient for safe home oxygen therapy.

PMID- 21896176
TI  - The presence of a lipoma in the Eustachian tube: a case report.
AB  - INTRODUCTION: The incidence of lipoma in the Eustachian tube is very rare, and to
      the best of our knowledge, has not been reported in the literature. Tumors that
      form in the cartilaginous portion of the Eustachian tube can be successfully
      removed by an endoscopic approach. CASE PRESENTATION: We report an incidentally
      detected lipoma of the Eustachian tube in a 34-year-old Asian woman with a six
      year history of persistent otitis media in her right ear. Our patient underwent
      surgery five years ago for the possibility of a choanal polyp, but her ear
      symptoms continued to be problematic following the surgery. Our patient was
      examined at our hospital, and computed tomography revealed a well-defined,
      hypodense, non-enhancing lesion involving the right Eustachian tube, measuring
      1.6 * 2.4 cm. The mass was excised using an endoscopic approach, and was found to
      originate from the cartilaginous portion of the Eustachian tube. The tumor was
      sent for histopathologic evaluation. The postoperative course went smoothly, and
      our patient recovered during follow-up over the next five months. CONCLUSION:
      Lipoma of the Eustachian tube is very rare compared with other tumors. Improved
      radiologic modalities aid the diagnosis of this benign tumor. Endoscopic removal
      of the tumor is possible and has helped in early recovery.

PMID- 21896177
TI  - Adenoid cystic carcinoma intermingled with ductal carcinoma of the breast: a case
      report and review of the literature.
AB  - INTRODUCTION: Adenoid cystic cancer of the breast is a rare condition, and even
      rarer are the cases where it is histologically mixed with other variants of
      cancer within a single lesion. In this report, one of the few cases of mixed
      adenoid cystic breast cancer intermingled with the infiltrating ductal variant is
      presented. A subsequent review of the relevant literature presents the existing
      experience in treating mixed breast cancers with adenoid cystic components with
      regard to diagnosis, treatment, and prognosis. CASE PRESENTATION: We describe a
      case of mixed adenoid cystic cancer of the breast with infiltrating ductal
      carcinoma in a 67-year-old Caucasian woman who underwent mastectomy with sentinel
      node biopsy. CONCLUSION: Surgery remains the cornerstone of treatment of these
      patients, and radiotherapy is administered when breast-conserving treatment is
      undertaken or a large tumor with affected lymph nodes is present. Hormonal
      treatment does not have a role, as estrogen receptors are always absent from both
      tumor components. Chemotherapy is nearly always administered on the basis of
      estrogen receptor and progesterone negativity and the more aggressive potential
      of the non-adenoid cystic component. The de-differentiation of an indolent type
      of cancer to a more aggressive one may affect the prognosis.

PMID- 21896178
TI  - Abiotrophia defectiva knee prosthesis infection: A case report.
AB  - BACKGROUND: Abiotrophia species have rarely been implicated in osteoarticular
      infections. We report one case of an A. defectiva knee prosthesis infection. CASE
      PRESENTATION: A 71-year-old man of Italian origin presented with pain and
      swelling of the knee four years after the implantation of a total knee
      replacement prosthesis. While standard culturing of the synovial fluid resulted
      in no isolation of microorganisms, the direct inoculation of the synovial fluid
      into a rich culture medium resulted in the identification of A. defectiva by
      polymerase chain reaction sequencing. Repeated attempts of culturing
      microorganisms from blood were negative, and echocardiograms and colonoscopies
      were unremarkable. High-dose amoxicillin for nine months and a two-stage
      replacement of the knee prosthesis led to full patient recovery by the time of
      the 12-month follow-up examination. CONCLUSIONS: Because Abiotrophia spp. are
      fastidious microorganisms, it is likely that cases of Abiotrophia orthopedic
      infection are misdiagnosed as culture-negative infections. Direct inoculation of
      synovial fluids into rich broth medium and further polymerase chain reaction
      based detection of culture-negative synovial fluids are key tests for accurate
      documentation and detection of these infections.

PMID- 21896179
TI  - Obstructive jaundice secondary to pancreatic head adenocarcinoma in a young
      teenage boy: a case report.
AB  - INTRODUCTION: Pancreatic adenocarcinoma is extremely rare in childhood. We report
      a case of metastatic pancreatic adenocarcinoma in a 13-year-old boy, revealed by
      jaundice. CASE PRESENTATION: A 13-year-old Moroccan boy was admitted with
      obstructive jaundice to the children's Hospital of Rabat, Department of Pediatric
      Oncology. Laboratory study results showed a high level of total and conjugated
      bilirubin. Computerized tomography of the abdomen showed a dilatation of the
      intra-hepatic and extra-hepatic bile ducts with a tissular heterogeneous tumor of
      the head of the pancreas and five hepatic lesions. Biopsy of a liver lesion was
      performed, and a histopathological examination of the sample confirmed the
      diagnosis of metastatic ductal adenocarcinoma of the pancreas. Our patient
      underwent a palliative biliary derivation. After that, chemotherapy was
      administered (5-fluorouracil and epirubicin), however no significant response to
      treatment was noted and our patient died six months after diagnosis. CONCLUSION:
      Malignant pancreatic tumors, especially ductal carcinomas, are exceedingly rare
      in the pediatric age group and their clinical features and treatment usually go
      unappreciated by most pediatric oncologists and surgeons.

PMID- 21896180
TI  - Lumbar disc herniation in three patients with cystic fibrosis: a case series.
AB  - INTRODUCTION: To date, lumbar disc herniation has not been reported in the
      context of cystic fibrosis even though back pain and musculoskeletal problems are
      very common in patients with cystic fibrosis. CASE PRESENTATION: We report on
      three patients with cystic fibrosis who experienced lumbar disc herniation in the
      course of their disease at ages 19 to 21 years (a 22-year-old Caucasian man, a 23
      year-old Caucasian man, and a 21-year-old Caucasian woman). Our third patient
      eventually died because of her deteriorated pulmonary situation, which was
      influenced by the lumbar disc herniation as it was not possible for her to
      perform pulmonary drainage techniques properly because of the pain. CONCLUSIONS:
      Lumbar disc herniation can lead to a vicious cycle for patients with cystic
      fibrosis as it may promote pulmonary infections. This report highlights the need
      to investigate patients correctly.

PMID- 21896181
TI  - Validation aspects of the health of the nation outcome scales.
AB  - BACKGROUND: The purpose of the current study was the psychometric evaluation of
      the Health of the Nation Outcome Scales (HoNOS), an instrument developed to meet
      the necessity of a clinically acceptable outcome scale for routine use in mental
      illness services. METHODS: The study participants included 2,162 outpatients and
      residential inpatients (rated on the HoNOS on three occasions during the year
      2000) with a range of mental illnesses in different diagnostic groups from ten
      Mental Health Departments, located in the area of Milan (Italy). Principal
      Component Analysis, Confirmatory Factor Analysis, Discriminant Analysis and
      Partial Credit Rasch Model were used to assess two sources of validity: the
      internal structure and the relationships with other variables. RESULTS: The
      results of the 12-item HoNOS demonstrate a significant departure from uni
      dimensionality, confirmed by the Rasch analysis (which identified three
      misfitting items). However, HoNOS scores demonstrate stability and precision of
      item difficulties over time. Discriminant analysis showed that HoNOS scores have
      an acceptable level of discriminatory power in predicting the severity of
      patients' conditions (as represented by setting). CONCLUSIONS: It was concluded
      that the Italian version of the HoNOS does not measure a single, underlying
      construct of mental health status. The internal structure validity analysis
      recommends a note of caution to use a summary index of the HoNOS scores, given
      the presence of multidimensionality and misfit. Nonetheless, the finding that the
      instrument is more multidimensional than unidimensional does not preclude the use
      of the HoNOS as a clinically valid tool for routine outcome assessment. In fact,
      item scores have demonstrated sufficient reliability (over diagnostic groups and
      care settings) and high precision in time, indicating that HoNOS items can be
      utilized as valid measurement instruments in longitudinal analyses.

PMID- 21896182
TI  - Transdifferentiation from cornea to lens in Xenopus laevis depends on BMP
      signalling and involves upregulation of Wnt signalling.
AB  - BACKGROUND: Surgical removal of the lens from larval Xenopus laevis results in a
      rapid transdifferention of central corneal cells to form a new lens. The trigger
      for this process is understood to be an induction event arising from the
      unprecedented exposure of the cornea to the vitreous humour that occurs following
      lens removal. The molecular identity of this trigger is unknown. RESULTS: Here,
      we have used a functional transgenic approach to show that BMP signalling is
      required for lens regeneration and a microarray approach to identify genes that
      are upregulated specifically during this process. Analysis of the array data
      strongly implicates Wnt signalling and the Pitx family of transcription factors
      in the process of cornea to lens transdifferentiation. Our analysis also captured
      several genes associated with congenital cataract in humans. Pluripotency genes,
      in contrast, were not upregulated, supporting the idea that corneal cells
      transdifferentiate without returning to a stem cell state. Several genes from the
      array were expressed in the forming lens during embryogenesis. One of these,
      Nipsnap1, is a known direct target of BMP signalling. CONCLUSIONS: Our results
      strongly implicate the developmental Wnt and BMP signalling pathways in the
      process of cornea to lens transdifferentiation (CLT) in Xenopus, and suggest
      direct transdifferentiation between these two anterior eye tissues.

PMID- 21896183
TI  - Mitochondrial genomes and Doubly Uniparental Inheritance: new insights from
      Musculista senhousia sex-linked mitochondrial DNAs (Bivalvia Mytilidae).
AB  - BACKGROUND: Doubly Uniparental Inheritance (DUI) is a fascinating exception to
      matrilinear inheritance of mitochondrial DNA (mtDNA). Species with DUI are
      characterized by two distinct mtDNAs that are inherited either through females (F
      mtDNA) or through males (M-mtDNA). DUI sex-linked mitochondrial genomes share
      several unusual features, such as additional protein coding genes and unusual
      gene duplications/structures, which have been related to the functionality of
      DUI. Recently, new evidence for DUI was found in the mytilid bivalve Musculista
      senhousia. This paper describes the complete sex-linked mitochondrial genomes of
      this species. RESULTS: Our analysis highlights that both M and F mtDNAs share
      roughly the same gene content and order, but with some remarkable differences.
      The Musculista sex-linked mtDNAs have differently organized putative control
      regions (CR), which include repeats and palindromic motifs, thought to provide
      sites for DNA-binding proteins involved in the transcriptional machinery.
      Moreover, in male mtDNA, two cox2 genes were found, one (M-cox2b) 123bp longer.
      CONCLUSIONS: The complete mtDNA genome characterization of DUI bivalves is the
      first step to unravel the complex genetic signals allowing Doubly Uniparental
      Inheritance, and the evolutionary implications of such an unusual transmission
      route in mitochondrial genome evolution in Bivalvia. The observed redundancy of
      the palindromic motifs in Musculista M-mtDNA may have a role on the process by
      which sperm mtDNA becomes dominant or exclusive of the male germline of DUI
      species. Moreover, the duplicated M-COX2b gene may have a different, still
      unknown, function related to DUI, in accordance to what has been already proposed
      for other DUI species in which a similar cox2 extension has been hypothesized to
      be a tag for male mitochondria.

PMID- 21896184
TI  - The somatostatinergic system in the mammalian cochlea.
AB  - BACKGROUND: Little is known about expression and function of the
      somatostatinergic system in the mammalian cochlea. We have previously shown that
      somatostatin administration may have a protective effect on gentamicin-induced
      hair cell loss. In this study, we have analyzed the cochlear expression of
      somatostatin receptor 1 (SST1) and somatostatin receptor 2 (SST2) at both the
      mRNA and the protein level in wild-type mice, as well as in SST1 and SST2 knock
      out (KO) mice and in cultivated neurosensory cells. RESULTS: We demonstrate that
      the somatostatin receptors SST1 and SST2 are specifically expressed in outer and
      inner hair cells (HCs) of the organ of Corti (OC), as well as in defined
      supporting cells. The expression of SST1 and SST2 receptors in cultivated P5
      mouse OC explants was similar to their expression in inner and outer hair cells.
      Somatostatin itself was not expressed in the mammalian cochlea, suggesting that
      somatostatin reaches its receptors either through the blood-labyrinthine barrier
      from the systemic circulation or via the endolymphatic duct from the
      endolymphatic sac. We used mice with a deletion of either SST1 or SST2 to learn
      more about the regulation of SST1 and SST2 receptor expression. We demonstrate
      that in SST1 KO mice, SST2 was expressed in outer HCs and Deiters' cells, but not
      in pillar cells or inner HCs, as compared with wild-type mice. In contrast, in
      SST2 KO mice, the expression pattern of the SST1 receptor was not altered
      relative to wild-type mice. CONCLUSIONS: These findings reveal that somatostatin
      receptors demonstrate specific expression in HCs and supporting cells of the
      mouse cochlea, and that absence of SST1 alters the expression of SST2. This
      specific expression pattern suggests that somatostatin receptors may have
      important functional roles in the inner ear.

PMID- 21896185
TI  - The development of the adult intestinal stem cells: Insights from studies on
      thyroid hormone-dependent amphibian metamorphosis.
AB  - Adult organ-specific stem cells are essential for organ homeostasis and repair
      in adult vertebrates. The intestine is one of the best-studied organs in this
      regard. The intestinal epithelium undergoes constant self-renewal throughout
      adult life across vertebrates through the proliferation and subsequent
      differentiation of the adult stem cells. This self-renewal system is established
      late during development, around birth, in mammals when endogenous thyroid hormone
      (T3) levels are high. Amphibian metamorphosis resembles mammalian postembryonic
      development around birth and is totally dependent upon the presence of high
      levels of T3. During this process, the tadpole intestine, predominantly a
      monolayer of larval epithelial cells, undergoes drastic transformation. The
      larval epithelial cells undergo apoptosis and concurrently, adult epithelial
      stem/progenitor cells develop de novo, rapidly proliferate, and then
      differentiate to establish a trough-crest axis of the epithelial fold, resembling
      the crypt-villus axis in the adult mammalian intestine. We and others have
      studied the T3-dependent remodeling of the intestine in Xenopus laevis. Here we
      will highlight some of the recent findings on the origin of the adult intestinal
      stem cells. We will discuss observations suggesting that liganded T3 receptor
      (TR) regulates cell autonomous formation of adult intestinal progenitor cells and
      that T3 action in the connective tissue is important for the establishment of the
      stem cell niche. We will further review evidence suggesting similar T3-dependent
      formation of adult intestinal stem cells in other vertebrates.

PMID- 21896186
TI  - Localization of DIR1 at the tissue, cellular and subcellular levels during
      Systemic Acquired Resistance in Arabidopsis using DIR1:GUS and DIR1:EGFP
      reporters.
AB  - BACKGROUND: Systemic Acquired Resistance (SAR) is an induced resistance response
      to pathogens, characterized by the translocation of a long-distance signal from
      induced leaves to distant tissues to prime them for increased resistance to
      future infection. DEFECTIVE in INDUCED RESISTANCE 1 (DIR1) has been hypothesized
      to chaperone a small signaling molecule to distant tissues during SAR in
      Arabidopsis. RESULTS: DIR1 promoter:DIR1-GUS/dir1-1 lines were constructed to
      examine DIR1 expression. DIR1 is expressed in seedlings, flowers and ubiquitously
      in untreated or mock-inoculated mature leaf cells, including phloem sieve
      elements and companion cells. Inoculation of leaves with SAR-inducing avirulent
      or virulent Pseudomonas syringae pv tomato (Pst) resulted in Type III Secretion
      System-dependent suppression of DIR1 expression in leaf cells. Transient
      expression of fluorescent fusion proteins in tobacco and intercellular washing
      fluid experiments indicated that DIR1's ER signal sequence targets it for
      secretion to the cell wall. However, DIR1 expressed without a signal sequence
      rescued the dir1-1 SAR defect, suggesting that a cytosolic pool of DIR1 is
      important for the SAR response. CONCLUSIONS: Although expression of DIR1
      decreases during SAR induction, the protein localizes to all living cell types of
      the vasculature, including companion cells and sieve elements, and therefore DIR1
      is well situated to participate in long-distance signaling during SAR.

PMID- 21896188
TI  - Early-onset ventilator-associated pneumonia incidence in intensive care units: a
      surveillance-based study.
AB  - BACKGROUND: The incidence of ventilator-associated pneumonia (VAP) within the
      first 48 hours of intensive care unit (ICU) stay has been poorly investigated.
      The objective was to estimate early-onset VAP occurrence in ICUs within 48 hours
      after admission. METHODS: We analyzed data from prospective surveillance between
      01/01/2001 and 31/12/2009 in 11 ICUs of Lyon hospitals (France). The inclusion
      criteria were: first ICU admission, not hospitalized before admission, invasive
      mechanical ventilation during first ICU day, free of antibiotics at admission,
      and ICU stay >= 48 hours. VAP was defined according to a national protocol. Its
      incidence was the number of events per 1,000 invasive mechanical ventilation
      days. The Poisson regression model was fitted from day 2 (D2) to D8 to incident
      VAP to estimate the expected VAP incidence from D0 to D1 of ICU stay. RESULTS:
      Totally, 367 (10.8%) of 3,387 patients in 45,760 patient-days developed VAP
      within the first 9 days. The predicted cumulative VAP incidence at D0 and D1 was
      5.3 (2.6-9.8) and 8.3 (6.1-11.1), respectively. The predicted cumulative VAP
      incidence was 23.0 (20.8-25.3) at D8. The proportion of missed VAP within 48
      hours from admission was 11% (9%-17%). CONCLUSIONS: Our study indicates
      underestimation of early-onset VAP incidence in ICUs, if only VAP occurring >= 48
      hours are considered to be hospital-acquired. Clinicians should be encouraged to
      develop a strategy for early detection after ICU admission.

PMID- 21896187
TI  - The reliability of assigning individuals to cognitive states using the Mini
      Mental-State Examination: a population-based prospective cohort study.
AB  - BACKGROUND: Previous investigations of test re-test reliability of the Mini
      Mental State Examination (MMSE) have used correlations and statistics such as
      Cronbach's alpha to assess consistency. In practice, the MMSE is usually used to
      group individuals into cognitive states. The reliability of this grouping (state
      based approach) has not been fully explored. METHODS: MMSE data were collected on
      a subset of 2,275 older participants (>= 65 years) from the population-based
      Medical Research Council Cognitive Function and Ageing Study. Two measurements
      taken approximately two months apart were used to investigate three state-based
      categorisations. Descriptive statistics were used to determine how many people
      remained in the same cognitive group or went up or down groups. Weighted logistic
      regression was used to identify predictive characteristics of those who moved
      group. RESULTS: The proportion of people who remained in the same MMSE group at
      screen and follow-up assessment ranged from 58% to 78%. The proportion of
      individuals who went up one or more groups was roughly equal to the proportion
      that went down one or more groups; most of the change occurred when measurements
      were close to the cut-points. There was no consistently significant predictor for
      changing cognitive group. CONCLUSION: A state-based approach to analysing the
      reliability of the MMSE provided similar results to correlation analyses. State
      based models of cognitive change or individual trajectory models using raw scores
      need multiple waves to help overcome natural variation in MMSE scores and to help
      identify true cognitive change.

PMID- 21896189
TI  - The relationship of ethnicity to the prevalence and management of hypertension
      and associated chronic kidney disease.
AB  - BACKGROUND: The effect of ethnicity on the prevalence and management of
      hypertension and associated chronic kidney (CKD) disease in the UK is unknown.
      METHODS: We performed a cross sectional study of 49,203 adults with hypertension
      to establish the prevalence and management of hypertension and associated CKD by
      ethnicity. Routinely collected data from general practice hypertension registers
      in 148 practices in London between 1/1/07 and 31/3/08 were analysed. RESULTS: The
      crude prevalence of hypertension was 9.5%, and by ethnicity was 8.2% for White,
      11.3% for South Asian and 11.1% for Black groups. The prevalence of CKD stages 3
      5 among those with hypertension was 22%. Stage 3 CKD was less prevalent in South
      Asian groups (OR 0.77, 95% CI 0.67 - 0.88) compared to Whites (reference
      population) with Black groups having similar rates to Whites. The prevalence of
      severe CKD (stages 4-5) was higher in the South Asian group (OR 1.53, 95% CI 1.17
      - 2.0) compared to Whites, but did not differ between Black and White groups. In
      the whole hypertension cohort, achievement of target blood pressure (< 140/90
      mmHg) was better in South Asian (OR 1.43, 95% CI 1.28 - 1.60) and worse in Black
      groups (OR 0.79, 95% CI 0.74 - 0.84) compared to White patients. Hypertensive
      medication was prescribed unequally among ethnic groups for any degree of blood
      pressure control. CONCLUSIONS: Significant variations exist in the prevalence of
      hypertension and associated CKD and its management between the major ethnic
      groups. Among those with CKD less than 50% were treated to a target BP of <=
      130/80 mmHg. Rates of ACE-I/ARB prescribing for those with CKD were less than
      optimal, with the lowest rates (58.5%) among Black groups.

PMID- 21896190
TI  - The costs in provision of haemodialysis in a developing country: a multi-centered
      study.
AB  - BACKGROUND: Chronic Kidney Disease is a major public health problem worldwide
      with enormous cost burdens on health care systems in developing countries. We
      aimed to provide a detailed analysis of the processes and costs of haemodialysis
      in Sri Lanka and provide a framework for modeling similar financial audits.
      METHODS: This prospective study was conducted at haemodialysis units of three
      public and two private hospitals in Sri Lanka for two months in June and July
      2010. Cost of drugs and consumables for the three public hospitals were obtained
      from the price list issued by the Medical Supplies Division of the Department of
      Health Services, while for the two private hospitals they were obtained from
      financial departments of the respective hospitals. Staff wages were obtained from
      the hospital chief accountant/chief financial officers. The cost of electricity
      and water per month was calculated directly with the assistance of expert
      engineers. An apportion was done from the total hospital costs of administration,
      cleaning services, security, waste disposal and, laundry and sterilization for
      each unit. RESULTS: The total number of dialysis sessions (hours) at the five
      hospitals for June and July were 3341 (12959) and 3386 (13301) respectively. Drug
      and consumables costs accounted for 70.4-84.9% of the total costs, followed by
      the wages of the nursing staff at each unit (7.8-19.7%). The mean cost of a
      dialysis session in Sri Lanka was LKR 6,377 (US$ 56). The annual cost of
      haemodialysis for a patient with chronic renal failure undergoing 2-3 dialysis
      session of four hours duration per week was LKR 663,208-994,812 (US$ 5,869
      8,804). At one hospital where facilities are available for the re-use of
      dialyzers (although not done during study period) the cost of consumables would
      have come down from LKR 5,940,705 to LKR 3,368,785 (43% reduction) if the method
      was adopted, reducing costs of haemodialysis per hour from LKR 1,327 at present
      to LKR 892 (33% reduction). CONCLUSIONS: This multi-centered study demonstrated
      that the costs of haemodialysis in a developing country remained significantly
      lower compared to developed countries. However, it still places a significant
      burden on the health care sector, whilst possibility of further cost reduction
      exists.

PMID- 21896191
TI  - An examination of cancer-related fatigue through proposed diagnostic criteria in
      a sample of cancer patients in Taiwan.
AB  - BACKGROUND: Fatigue among cancer patients has often been reported in the
      literature; however, great variations have been documented, ranging from 15% to
      90%, probably due to the lack of a widely accepted definition and established
      diagnostic criteria for cancer-related fatigue. The objective of this study was
      to evaluate the proposed International Statistical Classification of Diseases and
      Related Health Problems (10th revision) (ICD-10) criteria in a sample of cancer
      patients from a medical center and a regional teaching hospital in northern
      Taiwan. More accurate prevalence estimates of CRF may result in improved
      diagnoses and management of one of the most common symptoms associated with
      cancer and its treatment. METHODS: Since self-reporting from patients is the most
      effective and efficient method to measure fatigue, the ICD-10 criteria for
      fatigue were used. The ICD-10 criteria questionnaire was translated into Chinese
      and was approved by experts. Patients were recruited from outpatient palliative
      and oncology clinics and from palliative and oncology inpatient units. RESULTS:
      Of the 265 cancer patients that were interviewed between 21 October 2008 and 28
      October 2009, 228 (86%) reported having at least 2 weeks of fatigue in the past
      month, and further evaluation with the ICD-10 criteria showed that 132 (49.8%)
      had cancer-related fatigue. Internal consistency was very good, which was
      indicated by a Cronbach alpha of 0.843. CONCLUSION: The prevalence of diagnosable
      CRF in the patients in this sample, of whom most were under palliative treatment,
      was 49.8%, which was probably somewhat lower than in some of the previous reports
      that have used less-strict criteria. In addition, among the various criteria of
      the proposed diagnostic criteria, the most frequently reported symptoms in our
      sample populations were regarding sleep disturbance and physical factors.
      Although they will require further replication in other samples, these formal
      diagnostic criteria can serve as a step toward a common language and a better
      understanding of the severity range of CRF.

PMID- 21896192
TI  - Inhibition of radiation induced migration of human head and neck squamous cell
      carcinoma cells by blocking of EGF receptor pathways.
AB  - BACKGROUND: Recently it has been shown that radiation induces migration of glioma
      cells and facilitates a further spread of tumor cells locally and systemically.
      The aim of this study was to evaluate whether radiotherapy induces migration in
      head and neck squamous cell carcinoma (HNSCC). A further aim was to investigate
      the effects of blocking the epidermal growth factor receptor (EGFR) and its
      downstream pathways (Raf/MEK/ERK, PI3K/Akt) on tumor cell migration in vitro.
      METHODS: Migration of tumor cells was assessed via a wound healing assay and
      proliferation by a MTT colorimeritric assay using 3 HNSCC cell lines (BHY, CAL
      27, HN). The cells were treated with increasing doses of irradiation (2 Gy, 5 Gy,
      8 Gy) in the presence or absence of EGF, EGFR-antagonist (AG1478) or inhibitors
      of the downstream pathways PI3K (LY294002), mTOR (rapamycin) and MEK1 (PD98059).
      Biochemical activation of EGFR and the downstream markers Akt and ERK were
      examined by Western blot analysis. RESULTS: In absence of stimulation or
      inhibition, increasing doses of irradiation induced a dose-dependent enhancement
      of migrating cells (p < 0.05 for the 3 HNSCC cell lines) and a decrease of cell
      proliferation (p < 0.05 for the 3 HNSCC cell lines). The inhibition of EGFR or
      the downstream pathways reduced cell migration significantly (almost all p < 0.05
      for the 3 HNSCC cell lines). Stimulation of HNSCC cells with EGF caused a
      significant increase in migration (p < 0.05 for the 3 HNSCC cell lines). After
      irradiation alone a pronounced activation of EGFR was observed by Western blot
      analysis. CONCLUSION: Our results demonstrate that the EGFR is involved in
      radiation induced migration of HNSCC cells. Therefore EGFR or the downstream
      pathways might be a target for the treatment of HNSCC to improve the efficacy of
      radiotherapy.

PMID- 21896193
TI  - Risk factors for respiratory work disability in a cohort of pulp mill workers
      exposed to irritant gases.
AB  - BACKGROUND: The association between chronic respiratory diseases and work
      disability has been demonstrated a number of times over the past 20 years, but
      still little is known about work disability in occupational cohorts of workers
      exposed to respiratory irritants. This study investigated job or task changes due
      to respiratory problems as an indicator of work disability in pulp mill workers
      occupationally exposed to irritants. METHODS: Data about respiratory symptoms and
      disease diagnoses, socio-demographic variables, occupational exposures, gassing
      episodes, and reported work changes due to respiratory problems were collected
      using a questionnaire answered by 3226 pulp mill workers. Information about work
      history and departments was obtained from personnel files. Incidence and hazard
      ratios for respiratory work disability were calculated with 95% confidence
      intervals (CI). RESULTS: The incidence of respiratory work disability among these
      pulp mill workers was 1.6/1000 person-years. The hazard ratios for respiratory
      work disability were increased for workers reporting gassings (HR 5.3, 95% CI 2.7
      10.5) and for those reporting physician-diagnosed asthma, chronic bronchitis, and
      chronic rhinitis, when analyzed in the same model. CONCLUSIONS: This cohort study
      of pulp mill workers found that irritant peak exposure during gassing episodes
      was a strong predictor of changing work due to respiratory problems, even after
      adjustment for asthma, chronic bronchitis, and chronic rhinitis.

PMID- 21896194
TI  - Perspectives on child diarrhoea management and health service use among ethnic
      minority caregivers in Vietnam.
AB  - BACKGROUND: In Vietnam, primary government health services are now accessible for
      the whole population including ethnic minority groups (EMGs) living in rural and
      mountainous areas. However, little is known about EMGs' own perspectives on
      illness treatment and use of health services. This study investigates treatment
      seeking strategies for child diarrhoea among ethnic minority caregivers in
      Northern Vietnam in order to suggest improvements to health services for EMGs and
      other vulnerable groups. METHODS: The study obtained qualitative data from eight
      months of field work among four EMGs in lowland and highland villages in the
      Northern Lao Cai province. Triangulation of methods included in-depth interviews
      with 43 caregivers of pre-school children (six years and below) who had a case of
      diarrhoea during the past month, three focus group discussions (FGDs) with men,
      and two weeks of observations at two Communal Health Stations (CHGs). Data was
      content-analyzed by ordering data into empirically and theoretically inspired
      themes and sub-categories assisted by the software NVivo8. RESULTS: This study
      identified several obstacles for EMG caregivers seeking health services,
      including: gender roles, long travelling distances for highland villagers,
      concerns about the indirect costs of treatment and a reluctance to use government
      health facilities due to feelings of being treated disrespectfully by health
      staff. However, ethnic minority caregivers all recognized the danger signs of
      child diarrhoea and actively sought simultaneous treatment in different health
      care systems and home-based care. Treatments were selected by matching the
      perceived cause and severity of the disease with the 'compatibility' of different
      treatments to the child. CONCLUSIONS: In order to improve EMGs' use of government
      health services it is necessary to improve the communication skills of health
      staff and to acknowledge both EMGs' explanatory disease models and the
      significant socio-economic constraints they experience. Broader health promotion
      programs should address the significant gender roles preventing highland mothers
      from seeking health services and include family elders and fathers in future
      health promotion programs. Encouraging existing child health care practices,
      including continued breastfeeding during illness and the use of home-made
      rehydration solutions, also present important opportunities for future child
      health promotion.

PMID- 21896195
TI  - Program for expectant and new mothers: a population-based study of participation.
AB  - BACKGROUND: The Manitoba Healthy Baby Program is aimed at promoting pre- and
      perinatal health and includes two components: 1) prenatal income supplement; 2)
      community support programs. The goal of this research was to determine the uptake
      of these components by target groups. METHODS: Data on participation in each of
      the two program components were linked to data on all hospital births in Manitoba
      between 2004/05 through 2007/08. Descriptive analyses of participation by
      maternal characteristics were produced. Logistic regression analyses were
      conducted to identify factors associated with participation in the two programs.
      Separate regressions were run for two groups of women giving birth during the
      study period: 1) total population; 2) those receiving provincial income
      assistance during the prenatal period. RESULTS: Almost 30% of women giving birth
      in Manitoba received the Healthy Baby prenatal income supplement, whereas only
      12.6% participated in any community support programs. Over one quarter (26.4%) of
      pregnant women on income assistance did not apply for and receive the prenatal
      income supplement, despite all being eligible for it. Furthermore, 77.8% of women
      on income assistance did not participate in community support programs. Factors
      associated with both receipt of the prenatal benefit and participation in
      community support programs included lower SES, receipt of income assistance,
      obtaining adequate prenatal care, having completed high school and having
      depressive symptoms. Having more previous births was associated with higher odds
      of receiving the prenatal benefit, but lower odds of attending community support
      programs. Being married was associated with lower odds of receiving the prenatal
      benefit but higher odds of participating in community support programs.
      CONCLUSIONS: Although uptake of the Healthy Baby program in Manitoba is greater
      for women in groups at risk for poorer perinatal outcomes, a substantial number
      of women eligible for this program are not receiving it; efforts to reach these
      women should be enhanced.

PMID- 21896196
TI  - The clustering of health behaviours in Ireland and their relationship with mental
      health, self-rated health and quality of life.
AB  - BACKGROUND: Health behaviours do not occur in isolation. Rather they cluster
      together. It is important to examine patterns of health behaviours to inform a
      more holistic approach to health in both health promotion and illness prevention
      strategies. Examination of patterns is also important because of the increased
      risk of mortality, morbidity and synergistic effects of health behaviours. This
      study examines the clustering of health behaviours in a nationally representative
      sample of Irish adults and explores the association of these clusters with mental
      health, self-rated health and quality of life. METHODS: TwoStep Cluster analysis
      using SPSS was carried out on the SLAN 2007 data (national Survey of Lifestyle,
      Attitudes and Nutrition, n = 10,364; response rate =62%; food frequency n =
      9,223; cluster analysis n = 7,350). Patterns of smoking, drinking alcohol,
      physical activity and diet were considered. Associations with positive and
      negative mental health, quality of life and self-rated health were assessed.
      RESULTS: Six health behaviour clusters were identified: Former Smokers, 21.3% (n
      = 1,564), Temperate, 14.6% (n = 1,075), Physically Inactive, 17.8% (n = 1,310),
      Healthy Lifestyle, 9.3% (n = 681), Multiple Risk Factor, 17% (n = 1248), and
      Mixed Lifestyle, 20% (n = 1,472). Cluster profiles varied with men aged 18-29
      years, in the lower social classes most likely to adopt unhealthy behaviour
      patterns. In contrast, women from the higher social classes and aged 65 years and
      over were most likely to be in the Healthy Lifestyle cluster. Having healthier
      patterns of behaviour was associated with positive lower levels of psychological
      distress and higher levels of energy vitality. CONCLUSION: The current study
      identifies discernible patterns of lifestyle behaviours in the Irish population
      which are similar to those of our European counterparts. Healthier clusters
      (Former Smokers, Temperate and Healthy Lifestyle) reported higher levels of
      energy vitality, lower levels of psychological distress, better self-rated health
      and better quality of life. In contrast, those in the Multiple Risk Factor
      cluster had the lowest levels of energy and vitality and the highest levels of
      psychological distress. Identification of these discernible patterns because of
      their relationship with mortality, morbidity and longevity is important for
      identifying national and international health behaviour patterns.

PMID- 21896197
TI  - A unique protein profile of peripheral neutrophils from COPD patients does not
      reflect cytokine-induced protein profiles of neutrophils in vitro.
AB  - BACKGROUND: Inflammation, both local and systemic, is a hallmark of chronic
      obstructive pulmonary disease (COPD). Inflammatory mediators such as TNFalpha and
      GM-CSF are secreted by lung epithelium, alveolar macrophages and other
      inflammatory cells and are thought to be important contributors in the
      pathogenesis of COPD. Indeed, neutrophils are activated by these cytokines and
      these cells are one of the major inflammatory cell types recruited to the
      pulmonary compartment of COPD patients. Furthermore, these inflammatory mediators
      are found in the peripheral blood of COPD patients and, therefore, we
      hypothesized that TNFalpha/GM-CSF-induced protein profiles can be found in
      peripheral neutrophils of COPD patients. METHODS: Using fluorescence 2
      dimensional difference gel electrophoresis we investigated differentially
      regulated proteins in peripheral neutrophils from COPD patients and healthy age
      matched control subjects. Furthermore, protein profiles from COPD patients were
      compared with those of neutrophils of healthy age-matched controls that were
      stimulated with TNFalpha and/or GM-CSF in vitro. Protein gels were compared using
      DeCyder 7.0 software. RESULTS: We identified 7 significantly regulated protein
      spots between peripheral neutrophils from COPD patients and age-matched healthy
      control subjects. Stimulation of peripheral neutrophils with TNFalpha, GM-CSF or
      TNFalpha + GM-CSF in vitro resulted in 13, 20 and 22 regulated protein spots,
      respectively. However, these cytokine-induced protein differences did not
      correspond with the protein differences found in neutrophils from COPD patients.
      CONCLUSION: These results show that neutrophils from COPD patients have a unique
      protein profile compared to neutrophils from healthy age-matched controls.
      Furthermore, the neutrophil profiles of COPD patients do not reflect putative
      dominant signals induced by TNFalpha, GM-CSF or their combination. Our results
      indicate that systemic neutrophil responses in COPD patients are caused by a
      unique but subtle interplay between multiple inflammatory signals.

PMID- 21896198
TI  - Acute inhalation of hypertonic saline does not improve mucociliary clearance in
      all children with cystic fibrosis.
AB  - BACKGROUND: Little is known of how mucociliary clearance (MCC) in children with
      cystic fibrosis (CF) and normal pulmonary function compares with healthy adults,
      or how an acute inhalation of 7% hypertonic saline (HS) aerosol affects MCC in
      these same children. METHODS: We compared MCC in 12 children with CF and normal
      pulmonary function after an acute inhalation of 0.12% saline (placebo), or HS,
      admixed with the radioisotope 99 mtechnetium sulfur colloid in a double-blind,
      randomized, cross-over study. Mucociliary clearance on the placebo day in the
      children was also compared to MCC in 10 healthy, non-CF adults. Mucociliary
      clearance was quantified over a 90 min period, using gamma scintigraphy, and is
      reported as MCC at 60 min (MCC60) and 90 min (MCC90). RESULTS: Median
      [interquartile range] MCC60 and MCC90 in the children on the placebo visit were
      15.4 [12.4-24.5]% and 19.3 [17.3-27.8%]%, respectively, which were similar to the
      adults with 17.8 [6.4-28.7]% and 29.6 [16.1-43.5]%, respectively. There was no
      significant improvement in MCC60 (2.2 [-6.2-11.8]%) or MCC90 (2.3 [-1.2-10.5]%)
      with HS, compared to placebo. In addition, 5/12 and 4/12 of the children showed a
      decrease in MCC60 and MCC90, respectively, after inhalation of HS. A post hoc
      subgroup analysis of the change in MCC90 after HS showed a significantly greater
      improvement in MCC in children with lower placebo MCC90 compared to those with
      higher placebo MCC90 (p = 0.045). CONCLUSIONS: These data suggest that percent
      MCC varies significantly between children with CF lung disease and normal
      pulmonary functions, with some children demonstrating MCC values within the
      normal range and others showing MCC values that are below normal values. In
      addition, although MCC did not improve in all children after inhalation of HS,
      improvement did occur in children with relatively low MCC values after placebo.
      This finding suggests that acute inhalation of hypertonic saline may benefit a
      subset of children with low MCC values.

PMID- 21896199
TI  - Methyl-binding domain protein-based DNA isolation from human blood serum combines
      DNA analyses and serum-autoantibody testing.
AB  - BACKGROUND: Circulating cell free DNA in serum as well as serum-autoantibodies
      and the serum proteome have great potential to contribute to early cancer
      diagnostics via non invasive blood tests. However, most DNA preparation protocols
      destroy the protein fraction and therefore do not allow subsequent protein
      analyses. In this study a novel approach based on methyl binding domain protein
      (MBD) is described to overcome the technical difficulties of combining DNA and
      protein analysis out of one single serum sample. METHODS: Serum or plasma samples
      from 98 control individuals and 54 breast cancer patients were evaluated upon
      silica membrane- or MBD affinity-based DNA isolation via qPCR targeting potential
      DNA methylation markers as well as by protein-microarrays for tumor-autoantibody
      testing. RESULTS: In control individuals, an average DNA level of 22.8 +/- 25.7
      ng/ml was detected applying the silica membrane based protocol and 8.5 +/- 7.5
      ng/ml using the MBD-approach, both values strongly dependent on the serum sample
      preparation methods used. In contrast to malignant and benign tumor serum
      samples, cell free DNA concentrations were significantly elevated in sera of
      metastasizing breast cancer patients. Technical evaluation revealed that serum
      upon MBD-based DNA isolation is suitable for protein-array analyses when data are
      consistent to untreated serum samples. CONCLUSION: MBD affinity purification
      allows DNA isolations under native conditions retaining the protein function,
      thus for example enabling combined analyses of DNA methylation and autoantigene
      profiles from the same serum sample and thereby improving minimal invasive
      diagnostics.

PMID- 21896200
TI  - Trends of increase in western medical services in traditional medicine hospitals
      in China.
AB  - BACKGROUND: Compare changes in types of hospital service revenues between
      traditional Chinese medicine (TCM) hospitals and Western-medicine based general
      hospitals. METHODS: 97 TCM hospitals and 103 general hospitals were surveyed in
      years of 2000 and 2004. Six types of medical service revenue between the two
      types of hospitals were compared overtime. The national statistics from 1999 to
      2008 were also used as complementary evidence. RESULTS: For TCM hospitals, the
      percentage of service revenue from Western medicine increased from 44.3% to 47.4%
      while the percentage of service revenue from TCM declined from 26.4% to 18.8%
      from 1999 to 2004. Percentages of revenue from laboratory tests and surgical
      procedures for both types of hospitals increased and the discrepancy between the
      two types of hospitals was narrowed from 1999 to 2004. For TCM hospitals,
      revenues from laboratory tests increased from 3.64% to 5.06% and revenues from
      surgical procedures increased from 3.44% to 7.02%. General hospitals' TCM drug
      revenue in outpatient care declined insignificantly from 5.26% to 3.87%, while
      the decline for the TCM hospitals was significant from 19.73% to 13.77%. The
      national statistics from 1999 to 2008 showed similar trends that the percentage
      of revenue from Western medicine for TCM hospitals increased from 59.6% in 1999
      to 62.2% in 2003 and 66.1% in 2008 while the percentage of revenue from TCM for
      TCM hospitals decreased from 18.0% in 1999, 15.4% in 2003, and 13.7% in 2008.
      CONCLUSION: Western medicine has become a vital revenue source for TCM hospitals
      in the current Chinese health care environment where government subsidies to
      health care facilities have significantly declined. Policies need to encourage
      TCM hospitals to identify their own special and effective services, improve
      public perception, increase demand, strengthen financial sources, and ultimately
      make contributions to preserving one of the national treasures.

PMID- 21896201
TI  - The development and application of a new tool to assess the adequacy of the
      content and timing of antenatal care.
AB  - BACKGROUND: Current measures of antenatal care use are limited to initiation of
      care and number of visits. This study aimed to describe the development and
      application of a tool to assess the adequacy of the content and timing of
      antenatal care. METHODS: The Content and Timing of care in Pregnancy (CTP) tool
      was developed based on clinical relevance for ongoing antenatal care and
      recommendations in national and international guidelines. The tool reflects
      minimal care recommended in every pregnancy, regardless of parity or risk status.
      CTP measures timing of initiation of care, content of care (number of blood
      pressure readings, blood tests and ultrasound scans) and whether the
      interventions were received at an appropriate time. Antenatal care trajectories
      for 333 pregnant women were then described using a standard tool (the APNCU
      index), that measures the quantity of care only, and the new CTP tool. Both tools
      categorise care into 4 categories, from 'Inadequate' (both tools) to 'Adequate
      plus' (APNCU) or 'Appropriate' (CTP). Participants recorded the timing and
      content of their antenatal care prospectively using diaries. Analysis included an
      examination of similarities and differences in categorisation of care episodes
      between the tools. RESULTS: According to the CTP tool, the care trajectory of
      10,2% of the women was classified as inadequate, 8,4% as intermediate, 36% as
      sufficient and 45,3% as appropriate. The assessment of quality of care differed
      significantly between the two tools. Seventeen care trajectories classified as
      'Adequate' or 'Adequate plus' by the APNCU were deemed 'Inadequate' by the CTP.
      This suggests that, despite a high number of visits, these women did not receive
      the minimal recommended content and timing of care. CONCLUSIONS: The CTP tool
      provides a more detailed assessment of the adequacy of antenatal care than the
      current standard index. However, guidelines for the content of antenatal care
      vary, and the tool does not at the moment grade over-use of interventions as
      'Inappropriate'. Further work needs to be done to refine the content items prior
      to larger scale testing of the impact of the new measure.

PMID- 21896203
TI  - Mast cell activation and clinical outcome in pediatric cholelithiasis and biliary
      dyskinesia.
AB  - BACKGROUND: The current study was undertaken to determine the degree of
      activation of gallbladder mucosal mast cells, whether mast cell (MC) density or
      activation differ between patients with and without a positive clinical response
      to cholecystectomy, and whether either density or activation correlate with
      gallbladder emptying. RESULTS: Fifteen biliary dyskinesia (BD) and 13 symptomatic
      cholelithiasis (CL) patients undergoing cholecystectomy were prospectively
      enrolled. Gallbladder wall MC density (by immunohistochemistry) and activation
      (by electron microscopy) were determined. Clinical response was evaluated 30 days
      post-cholecystectomy on a 5-point Likert-type scale. A complete or nearly
      complete clinical response was seen in 100% of CL and in 87% of BD patients. The
      overall degranulation indices were 49.4 +/- 18.7% for CL patients and 44.2 +/-
      16.8% for BD patients. Neither MC density nor activation correlated with the
      gallbladder ejection fraction. A complete clinical response was associated with
      lower epithelial MC density. CONCLUSION: Cholecystectomy is efficacious in
      relieving pain in both CL and BD patients. BD and CL are associated not only with
      increased MC density but a moderate to high degree of MC activation. A possible
      relationship between MC density and outcome for BD warrants further
      investigation.

PMID- 21896204
TI  - Genetic screening of Fabry patients with EcoTILLING and HRM technology.
AB  - BACKGROUND: Anderson-Fabry disease (FD) is caused by a deficit of the alpha
      galactosidase A enzyme which leads to the accumulation of complex sphingolipids,
      especially globotriaosylceramide (Gb3), in all the cells of the body, causing the
      onset of a multi-systemic disease with poor prognosis in adulthood. In this
      article, we describe two alternative methods for screening the GLA gene which
      codes for the alpha-galactosidase A enzyme in subjects with probable FD in order
      to test analysis strategies which include or rely on initial pre-screening.
      FINDINGS: We analyzed 740 samples using EcoTILLING, comparing two mismatch
      specificendonucleases, CEL I and ENDO-1, while conducting a parallel screening of
      the same samples using HRM (High Resolution Melting). Afterwards, all samples
      were subjected to direct sequencing. Overall, we identified 12 different genetic
      variations: -10C>T, -12G>A, -30G>A, IVS2-76_80del5, D165H, C172Y, IVS4+16A>G,
      IVS4 +68 A>G, c.718_719delAA, D313Y, IVS6-22C>T, G395A. This was consistent with
      the high genetic heterogeneity found in FD patients and carriers. All of the
      mutations were detected by HRM, whereas 17% of the mutations were not found by
      EcoTILLING. The results obtained by EcoTILLING comparing the CEL I and ENDO-1
      endonucleases were perfectly overlapping. CONCLUSION: On the basis of its
      simplicity, flexibility, repeatability, and sensitivity, we believe thatHRM
      analysis of the GLA gene is a reliable presequencing screening tool. This method
      can be applied to any genomic feature to identify known and unknown genetic
      alterations, and it is ideal for conducting screening and population studies.

PMID- 21896202
TI  - Emerging therapies for severe asthma.
AB  - Many patients with asthma have poorly controlled symptoms, and particularly for
      those with severe disease, there is a clear need for improved treatments. Two
      recent therapies licensed for use in asthma are omalizumab, a humanized
      monoclonal antibody that binds circulating IgE antibody, and bronchial
      thermoplasty, which involves the delivery of radio frequency energy to the
      airways to reduce airway smooth muscle mass. In addition, there are new therapies
      under development for asthma that have good potential to reach the clinic in the
      next five years. These include biological agents targeting pro-inflammatory
      cytokines such as interleukin-5 and interleukin-13, inhaled ultra long-acting
      beta2-agonists and once daily inhaled corticosteroids. In addition, drugs that
      block components of the arachidonic acid pathway that targets neutrophilic asthma
      and CRTH2 receptor antagonists that inhibit the proinflammatory actions of
      prostaglandin D2 may become available. We review the recent progress made in
      developing viable therapies for severe asthma and briefly discuss the idea that
      development of novel therapies for asthma is likely to increasingly involve the
      assessment of genotypic and/or phenotypic factors.

PMID- 21896205
TI  - Identification of Phosphoglycerate Kinase 1 (PGK1) as a reference gene for
      quantitative gene expression measurements in human blood RNA.
AB  - BACKGROUND: Blood is a convenient sample and increasingly used for quantitative
      gene expression measurements with a variety of diseases including chronic fatigue
      syndrome (CFS). Quantitative gene expression measurements require normalization
      of target genes to reference genes that are stable and independent from variables
      being tested in the experiment. Because there are no genes that are useful for
      all situations, reference gene selection is an essential step to any quantitative
      reverse transcription-PCR protocol. Many publications have described appropriate
      genes for a wide variety of tissues and experimental conditions, however,
      reference genes that may be suitable for the analysis of CFS, or human blood RNA
      derived from whole blood as well as isolated peripheral blood mononuclear cells
      (PBMCs), have not been described. FINDINGS: Literature review and analyses of our
      unpublished microarray data were used to narrow down the pool of candidate
      reference genes to six. We assayed whole blood RNA from Tempus tubes and cell
      preparation tube (CPT)-collected PBMC RNA from 46 subjects, and used the geNorm
      and NormFinder algorithms to select the most stable reference genes.
      Phosphoglycerate kinase 1 (PGK1) was one of the optimal normalization genes for
      both whole blood and PBMC RNA, however, additional genes differed for the two
      sample types; Ribosomal protein large, P0 (RPLP0) for PBMC RNA and Peptidylprolyl
      isomerase B (PPIB) for whole blood RNA. We also show that the use of a single
      reference gene is sufficient for normalization when the most stable candidates
      are used. CONCLUSIONS: We have identified PGK1 as a stable reference gene for use
      with whole blood RNA and RNA derived from PBMC. When stable genes are selected it
      is possible to use a single gene for normalization rather than two or three.
      Optimal normalization will improve the ability of results from PBMC RNA to be
      compared with those from whole blood RNA and potentially allows comparison of
      gene expression results from blood RNA collected and processed by different
      methods with the intention of biomarker discovery. Results of this study should
      facilitate large-scale molecular epidemiologic studies using blood RNA as the
      target of quantitative gene expression measurements.

PMID- 21896208
TI  - A reaction-diffusion model of the receptor-toxin-antibody interaction.
AB  - BACKGROUND: It was recently shown that the treatment effect of an antibody can be
      described by a consolidated parameter which includes the reaction rates of the
      receptor-toxin-antibody kinetics and the relative concentration of reacting
      species. As a result, any given value of this parameter determines an associated
      range of antibody kinetic properties and its relative concentration in order to
      achieve a desirable therapeutic effect. In the current study we generalize the
      existing kinetic model by explicitly taking into account the diffusion fluxes of
      the species. RESULTS: A refined model of receptor-toxin-antibody (RTA)
      interaction is studied numerically. The protective properties of an antibody
      against a given toxin are evaluated for a spherical cell placed into a toxin
      antibody solution. The selection of parameters for numerical simulation
      approximately corresponds to the practically relevant values reported in the
      literature with the significant ranges in variation to allow demonstration of
      different regimes of intracellular transport. CONCLUSIONS: The proposed
      refinement of the RTA model may become important for the consistent evaluation of
      protective potential of an antibody and for the estimation of the time period
      during which the application of this antibody becomes the most effective. It can
      be a useful tool for in vitro selection of potential protective antibodies for
      progression to in vivo evaluation.

PMID- 21896206
TI  - Identification of H-2d restricted T cell epitope of foot-and-mouth disease virus
      structural protein VP1.
AB  - BACKGROUND: Foot-and-mouth disease (FMD) is a highly contagious and devastating
      disease affecting livestock that causes significant financial losses. Therefore,
      safer and more effective vaccines are required against Foot-and-mouth disease
      virus(FMDV). The purpose of this study is to screen and identify an H-2d
      restricted T cell epitope from the virus structural protein VP1, which is present
      with FMD. We therefore provide a method and basis for studying a specific FMDV T
      cell epitope. RESULTS: A codon-optimized expression method was adopted for
      effective expression of VP1 protein in colon bacillus. We used foot-and-mouth
      disease standard positive serum was used for Western blot detection of its
      immunogenicity. The VP1 protein was used for immunizing BALB/c mice, and spleen
      lymphocytes were isolated. Then, a common in vitro training stimulus was
      conducted for potential H-2Dd, H-2Kd and H-2Ld restricted T cell epitope on VP1
      proteins that were predicted and synthesized by using a bioinformatics method.
      The H-2Kd restricted T cell epitope pK1 (AYHKGPFTRL) and the H-2Dd restricted T
      cell epitope pD7 (GFIMDRFVKI) were identified using lymphocyte proliferation
      assays and IFN-gamma ELISPOT experiments. CONCLUSIONS: The results of this study
      lay foundation for studying the FMDV immune process, vaccine development, among
      other things. These results also showed that, to identify viral T cell epitopes,
      the combined application of bioinformatics and molecular biology methods is
      effective.

PMID- 21896207
TI  - A molecular and antigenic survey of H5N1 highly pathogenic avian influenza virus
      isolates from smallholder duck farms in Central Java, Indonesia during 2007-2008.
AB  - BACKGROUND: Indonesia is one of the countries most severely affected by H5N1
      highly pathogenic avian influenza (HPAI) virus in terms of poultry and human
      health. However, there is little information on the diversity of H5N1 viruses
      circulating in backyard farms, where chickens and ducks often intermingle. In
      this study, H5N1 virus infection occurring in 96 smallholder duck farms in
      central Java, Indonesia from 2007-2008 was investigated and the molecular and
      antigenic characteristics of H5N1 viruses isolated from these farms were
      analysed. RESULTS: All 84 characterised viruses belonged to H5N1 clade 2.1 with
      three virus sublineages being identified: clade 2.1.1 (1), clade 2.1.3 (80), and
      IDN/6/05-like viruses (3) that did not belong to any of the present clades. All
      three clades were found in ducks, while only clade 2.1.3 was isolated from
      chickens. There were no significant amino acid mutations of the hemagglutinin
      (HA) and neuraminidase (NA) sites of the viruses, including the receptor binding,
      glycosylation, antigenic and catalytic sites and NA inhibitor targets. All the
      viruses had polybasic amino acids at the HA cleavage site. No evidence of major
      antigenic variants was detected. Based on the HA gene, identical virus variants
      could be found on different farms across the study sites and multiple genetic
      variants could be isolated from HPAI outbreaks simultaneously or at different
      time points from single farms. HPAI virus was isolated from both ducks and
      chickens; however, the proportion of surviving duck cases was considerably higher
      than in chickens. CONCLUSIONS: The 2.1.3 clade was the most common lineage found
      in this study. All the viruses had sequence characteristic of HPAI, but
      negligible variations in other recognized amino acids at the HA and NA proteins
      which determine virus phenotypes. Multiple genetic variants appeared to be
      circulating simultaneously within poultry communities. The high proportion of
      live duck cases compared to chickens over the study period suggests that ducks
      are more likely to survive infection and they may better suit the role of long
      term maintenance host for H5N1. As some viruses were isolated from dead birds,
      there was no clear correlation between genetic variations and pathogenicity of
      these viruses.

PMID- 21896209
TI  - Heterogeneity of variance components for preweaning growth in Romane sheep due to
      the number of lambs reared.
AB  - BACKGROUND: The pre-weaning growth rate of lambs, an important component of meat
      market production, is affected by maternal and direct genetic effects. The French
      genetic evaluation model takes into account the number of lambs suckled by
      applying a multiplicative factor (1 for a lamb reared as a single, 0.7 for twin
      reared lambs) to the maternal genetic effect, in addition to including the
      birth*rearing type combination as a fixed effect, which acts on the mean.
      However, little evidence has been provided to justify the use of this
      multiplicative model. The two main objectives of the present study were to
      determine, by comparing models of analysis, 1) whether pre-weaning growth is the
      same trait in single- and twin-reared lambs and 2) whether the multiplicative
      coefficient represents a good approach for taking this possible difference into
      account. METHODS: Data on the pre-weaning growth rate, defined as the average
      daily gain from birth to 45 days of age on 29,612 Romane lambs born between 1987
      and 2009 at the experimental farm of La Sapiniere (INRA-France) were used to
      compare eight models that account for the number of lambs per dam reared in
      various ways. Models were compared using the Akaike information criteria.
      RESULTS: The model that best fitted the data assumed that 1) direct (maternal)
      effects correspond to the same trait regardless of the number of lambs reared, 2)
      the permanent environmental effects and variances associated with the dam depend
      on the number of lambs reared and 3) the residual variance depends on the number
      of lambs reared. Even though this model fitted the data better than a model that
      included a multiplicative coefficient, little difference was found between EBV
      from the different models (the correlation between EBV varied from 0.979 to
      0.999). CONCLUSIONS: Based on experimental data, the current genetic evaluation
      model can be improved to better take into account the number of lambs reared.
      Thus, it would be of interest to evaluate this model on field data and update the
      genetic evaluation model based on the results obtained.

PMID- 21896211
TI  - [Health inequalities: the time for action!].

PMID- 21896210
TI  - A cell factory of Bacillus subtilis engineered for the simple bioconversion of
      myo-inositol to scyllo-inositol, a potential therapeutic agent for Alzheimer's
      disease.
AB  - BACKGROUND: A stereoisomer of inositol, scyllo-inositol, is known as a promising
      therapeutic agent for Alzheimer's disease, since it prevents the accumulation of
      beta-amyloid deposits, a hallmark of the disease. However, this compound is
      relatively rare in nature, whereas another stereoisomer of inositol, myo
      inositol, is abundantly available. RESULTS: Bacillus subtilis possesses a unique
      inositol metabolism involving both stereoisomers. We manipulated the inositol
      metabolism in B. subtilis to permit the possible bioconversion from myo-inositol
      to scyllo-inositol. Within 48 h of cultivation, the engineered strain was able to
      convert almost half of 10 g/L myo-inositol to scyllo-inositol that accumulated in
      the culture medium. CONCLUSIONS: The engineered B. subtilis serves as a prototype
      of cell factory enabling a novel and inexpensive supply of scyllo-inositol.

PMID- 21896212
TI  - [Health priorities, regions, areas and citizens: the case of Franche-Comte].
AB  - How can users' associations promote direct citizen involvement in the debate over
      health priorities throughout a region and within local health areas? A survey was
      conducted by user representatives with the support of a group of researchers and
      academics, based on a questionnaire outlining 42 key priorities and a 43rd
      priority inviting an open response. The questionnaire was published between April
      12 and April 18 2010 in 14 local and regional newspapers throughout Franche
      Comte. In total, 962 responses were collected, though only 928 responses were
      included in the analysis as having originated from the Franche-Comte region. In
      decreasing order of importance, the five major priorities identified by
      respondents are: a decent home, a healthy diet, sufficient income, drinking
      water, and improved cancer prevention and control. Views from the different
      health areas within the region were found to reflect the views of the region as a
      whole, while emphasizing access to education. Health determinants were the most
      common priority emphasized by respondents, though a number of area-specific
      characteristics were also found. Public surveys may help regional health agencies
      and authorities to define or validate local and regional health priorities in
      addition to national priorities, with a view (in particular) to reducing health
      inequalities throughout the region and within the different health areas.

PMID- 21896213
TI  - [Home and leisure injuries among fifth-grade schoolchildren in 2004-2005].
AB  - A survey was conducted among a representative national sample of fifth-grade
      schoolchildren between September 2004 and June 2005. 97% of all injuries reported
      by 6,836 schoolchildren interviewed in Metropolitan France were home and leisure
      injuries (HLI). Quarterly incidence was established at 9.2 HLIs or traffic
      accidents per 100 children (confidence interval [8.3; 10.1]). One third of HLIs
      were found to occur at school, 20% at home, and 54% during a sport or physical
      activity. HLIs involved treatment in an emergency department in 60% of cases, a
      limitation of activities in 76% of cases, and exemption from physical education
      and sports in 57% of cases. The occurrence of severe HLIs was 1.4 times higher in
      children aged 11 and over ([1.03; 1.8] and in children who take part in sport on
      a regular basis ([1.1; 1.8]). The risk of a severe HLI was 1.8 times higher in
      children from families of four children or more ([1.1; 3.0]). No association was
      found between the occurrence of HLIs and gender, visual acuity and parents'
      occupational status. Based on data relating to fifth-grade schoolchildren, the
      results of this study require further research on specific age groups. Prevention
      efforts will need to reduce morbidity and mortality as a result of HLIs (over 250
      child deaths per year).

PMID- 21896215
TI  - [Doing more to earn more: cesarean sections based on three cases of exemption
      from payment in Senegal].
AB  - In 2007, the number of caesarean sections performed in Senegal increased by 124%
      compared to the number of caesarean sections recorded before the introduction of
      a C-section funding initiative in 2006. The rate of increase varies in different
      regions and hospitals, with some hospitals performing caesarean sections in over
      50% of deliveries. The purpose of this paper is to analyze the main reasons for
      high hospital caesarean section rates (i.e. above the national average) based on
      three cases of exemption from payment. The study is based on a qualitative method
      involving semi-structured interviews with healthcare and administrative staff and
      pregnant women in three healthcare institutions and interviews with central
      health authorities. Research indicates that high caesarean section rates are not
      directly linked to the C-section subsidy policy introduced in 2006. The
      perception of caesarean rates is more closely linked to the perception of
      population rates among healthcare professionals than to the perception of
      institutional (hospital) rates. Since population rates are very low, healthcare
      professionals tend to perform more caesarean sections. Among management staff,
      the financial returns of high caesarean section rates (in the three levels of
      exemption) represent a significant motivation for encouraging healthcare
      professionals to perform more C-sections. Despite these high rates, a normative
      discourse was found to be held by healthcare professionals, who tend to consider
      that their practices are aimed exclusively at saving the mother or the child.
      However, in the long term, high caesarean section rates may result in an increase
      of maternal deaths and go against MDG 5, aimed at reducing maternal mortality by
      3/4 by 2015.

PMID- 21896214
TI  - [Pesticide poisoning in Moroccan children: epidemiological and prognostic aspects
      (1990-2008)].
AB  - OBJECTIVE: The purpose of this paper is to describe the epidemiological profile
      of<np pagenum="196"/> acute pesticide poisoning in children (APP) treated by the
      Moroccan Poison Control Center (CAPM) and to analyze death cases in order to
      determine factors predictive of severity. METHOD: the study is based on a
      retrospective study of all cases of APP collected by the CAPM over a period of
      eighteen years (January 1990 to December 2008). Univariate analysis was performed
      to identify risk factors. RESULTS: 2,672 cases of childhood poisoning by
      pesticide were collected. The mean age was 5.6 +/- 4.57 years. The sex ratio was
      1.12. The cause of poisoning was accidental in 87.1% of cases, followed by
      attempted suicide (12.1%). Organophosphates were the most frequent poison
      (50.7%), followed by alpha-chloralose (26.5%). The case fatality rate was 3.3%.
      Mortality was attributed to organophosphates in 30 cases, followed by inorganic
      derivatives (7 cases) and carbamates (6 cases). A univariate analysis comparing
      survivors and groups who died showed that rural origin (p = 0.04), voluntary
      circumstances (p = 0.001), and the type of chemical class of pesticide (p <
      0.001) significantly influence fatal poisoning. CONCLUSION: Acute pesticide
      poisoning among children is a reality in Morocco. Preventive measures may be
      needed.

PMID- 21896216
TI  - [Community immersion in Lausanne: a different approach to teaching public
      health?].
AB  - Teaching community medicine represents a significant challenge for medical
      schools, which tend to struggle to promote interest in the issue among students.
      In 2009, the Lausanne medical school introduced a "community immersion" module
      specifically designed to address the issue. The new module requires students
      working in small groups under the supervision of a tutor to investigate a health
      question of their choice. The investigation involves conducting interviews with
      stakeholders (health professionals, patients, politicians, etc.), carrying out a
      survey, and presenting the results of the investigation in a "congress". An
      external evaluation showed that the objectives of the initiative had been largely
      achieved, with an increase of interest in community medicine for over 50% of
      students (based on a total cohort of 150 students) and a high level of
      satisfaction for over 90% of students and tutors. This paper presents the results
      of the initiative and its use for promoting community-oriented medicine.

PMID- 21896217
TI  - [Pregnancy and poly-drug use: changes in patient population and care, 1999-2008].
AB  - Changes in drug use in the general French population over the last decade have
      also been observed among pregnant women. There have also been significant changes
      in the treatment of substance users. Data relating to maternal drug use and the
      treatment of drug-using mothers were collected based on a retrospective cohort of
      170 newborns with mothers using at least two different substances. The decrease
      in the proportion of heroin-users, the rise of opiate maintenance treatments and
      cannabis, and the development of new forms of treatment are linked to shorter
      maternity stays for newborns and shorter treatments for neonatal abstinence
      syndrome. The percentage of preterm births and of children placed in foster care
      is also on the decrease. Changes in drug use among mothers and new forms of
      treatment given to mother-infant dyads may account for the decrease in treatment
      for NAS, the shorter length of hospital stays, and the decreasing number of
      children placed in foster care.

PMID- 21896218
TI  - [Global consensus on social accountability of medical schools].
AB  - A collaborative research project on the social accountability of medical schools
      based on the Delphi method was conducted by an international reference group
      composed of 130 representatives of the main associations of medical schools and
      medical education organizations throughout the world, in addition to experts
      invited to take part in a personal capacity. The project ended with a conference
      held in South Africa overseen by an independent adjudicator who was not an expert
      in the field. The event resulted in the unanimous adoption of a document entitled
      ?Global consensus on social accountability of medical schools'. The document
      emphases the importance of improving the capacity of medical schools to respond
      to the needs and challenges of health care for citizens and society in general,
      in line with the core values of quality, equity, relevance and effectiveness. The
      implications for reconsidering quality practices and for reviewing accreditation
      and evaluation criteria are presented.

PMID- 21896219
TI  - [Job retention and health issues: an example of personalized assistance in
      northern France].
AB  - "Sante Emploi Info Service" (Health and Employment Information Service) is a
      regional information service aimed at providing support and assistance to people
      who are struggling to perform their job effectively or to return to work as a
      result of a health problem. Through personalized assistance and follow-up, the
      service aims to help individuals to avoid professional exclusion, to provide
      accessible information, and to encourage networking between healthcare
      professionals and services specializing in job retention and vocational
      rehabilitation. In total, 1,392 calls have been received since the service opened
      in 2006, with most calls dealing with employment, income and legal matters and a
      range of psychological counseling issues. More than half of the proposed
      solutions have proved successful. The regional service (a unique initiative in
      France) is supported by Lille Regional Hospital and helps individuals suffering
      from health problems to overcome obstacles to job retention and vocational
      rehabilitation. The service also provides specifically-tailored information about
      legal procedures relating to professional integration and vocational
      rehabilitation.

PMID- 21896221
TI  - [Long life to health democracy!].

PMID- 21896222
TI  - [Issues of consultation for the first birth control: young women facing health
      professionals].
AB  - Contraceptives are commonly used in France. Through the words of young women,
      this article analyzes the representations they have of health professionals when
      they first request birth control. This article point out the importance of early
      contact with the medical profession at the beginning of contraception.

PMID- 21896223
TI  - [Prevalence and risk factors of attention disorders of professional drivers in
      Morocco].
AB  - We aimed to evaluate the prevalence and risk factors of professional drivers'
      vigilance disorders in Morocco. This transversal epidemiological multicentric
      study concerned 5,566 professional drivers of taxis (2,134), buses (1,158) and
      trucks (2,274). We used an anonymous individual questionnaire of 4 sections:
      socioprofessional and sanitary characteristics of drivers, working conditions,
      sleeping habits, symptoms of sleep problems and favouring factors. Drivers were a
      population at risk: high body mass index (62.2%), toxic habits (smoking: 50.6%;
      alcohol: 12.9%; cannabis use: 11.7%), pathological antecedents (27%) and
      consumption of psychotropic drugs (4%). Their working conditions were difficult
      and sleeping problems were frequent. The mean daily hours of work was 10.6 +/-
      1.6, and mean sleep duration 6.5 +/- 1.3 hr. Insomnia was 40.2%, abnormally high
      Epworth scores 36.3% and sleepiness when driving 53.4%. Information and education
      on the dangers of sleepiness while driving is necessary, as is respect for
      regulations on work duration. The extension of the occupational health system to
      this type of activity would help improve road security and protect the health of
      professional drivers and road users.

PMID- 21896225
TI  - [Estimated costs of the expanded program of immunization in the health district
      of Grand Bassam, Cote d'Ivoire].
AB  - The vaccines of the Expanded Immunization Program are administered free of charge
      to beneficiaries. However, these vaccines are purchased by countries and partners
      of immunization. These costs need to be estimated to be better understood. We
      conducted a descriptive cross-sectional study of the costs of the Expanded
      Immunization Program in the health district of Grand-Bassam from January 1 to
      December 31, 2006, with questions aiming to understand the costs from the point
      of view of the state and partners. We aimed to determine costs by level of
      expenditure, calculate the cost per child who received 3 doses of vaccine against
      Diphtheria-Tetanus-Pertussis-Hepatitis B and cost per strategy. Vaccines and
      injection supplies accounted for 49% of recurrent costs. Vehicles and motorcycles
      for transport accounted for 73% of non-recurrent costs. The recurrent cost per
      child who received 3 doses of the vaccine was 10 797 FCFA (16 euros). The
      recurrent cost per dose administered was 1,041 FCFA (1,58 euros) for the fixed
      strategy, 4,232 FCFA (6,45 euros) for the outreach strategy and 4,058 FCFA (6,18
      euros) for the mobile strategy. Because of the scarcity of financial resources,
      the Cote d'Ivoire government must strengthen efficient public-health measures,
      including vaccination.

PMID- 21896224
TI  - [Explarotory study about professional characteristics of suicide attempters].
AB  - We aimed to describe the professional characteristics of suicide attempters. One
      investigator asked 87 consecutive patients, aged 18 to 25 years, who had been
      hospitalized in a university hospital in Angers after having attempted suicide
      anytime during a 6.5-month period (November 2008-April 2009) to complete a
      questionnaire about their working conditions. The working conditions of both
      sexes were approximatively the same. Many patients described situations where
      work organization was known to produce given mental disorders. Patients
      hospitalized for suicide attempts are in professions that leaves them more
      stressed than the general population of workers (Sumer, Samotrace etc.). This
      evidence could favour a link between attempted suicide and mental factors of
      strain at work. The results of this study should be interpreted with caution
      because of the phenomena of circuitous data and small sample size.

PMID- 21896226
TI  - [Hemophilia patient education: teaching and assessment of 10 programs].
AB  - A group of health professionals and patients conducted a pedagogical assessment
      of Therapeutic Patient Education (TPE) in haemophilia in France, focused on 2
      main subjects: "the objectives and aims of TPE programs" and "the health
      professionals' ability to lead and contribute to TPE programs" (3). The use of a
      research laboratory and a participatory methodology allowed for identifying the
      assessment's challenges and contributed to its smooth running. TPE is starting to
      be integrated with medical care for patients, and a multidisciplinary approach
      better meets patients' educational needs. Two prerequisites for improving the
      pedagogical quality of these programs are self-reported patient needs and
      coordination of the TPE activities. The parties involved in this study are now
      better prepared to meet the ARS (4) TPE program specifications in haemophilia,
      and, importantly, are better prepared to undergo the assessment that takes place
      every 4 years.

PMID- 21896227
TI  - [Therapeutic patient education: the need for a comprehensive, coordinated and
      sutainable approach].
AB  - Therapeutic patient education has gradually developed for 20 years in France but
      not in a structured way. Today, therapeutic patient education has found legal
      consecration with the law of July 21,2009 (HPST), completed by a statute in
      August 2010. The development of chronic diseases therefore is monitored by a more
      global planning of the care, particularly in towns, with local coordination to
      meet the needs of the population and long-lasting financing.

PMID- 21896228
TI  - [Opinion of the National Federation of Education and Health Promotion on report
      "New approaches to public health prevention"].
AB  - In 2009, the Center for Strategic Analysis initiated a study, entitled
      Neurosciences and Public Policies, to assess the use of neurosciences in
      prevention policy. Subsequently, a report highlighted the inefficiency of the
      "traditional" prevention programs and the potential contribution of neurosciences
      to defining a new prevention approach. For the French National Federation for
      Health Education and Promotion, health promotion cannot be limited to a "counter
      manipulation" of consumers confronted with marketing strategies from the food and
      tobacco industries. Promoting health helps people increase control over the
      determinants of their health, by means of educational empowering strategies.

PMID- 21896230
TI  - Unmet needs in patients with epilepsy, following audit, educational intervention
      and the introduction of the New General Practice Contract.
AB  - BACKGROUND: Historically, epilepsy care has been documented as poor. The New
      Contract introduced epilepsy as a quality indicator from April 2004. AIM: To
      measure the unmet clinical needs in patients with epilepsy, following an audit,
      with educational intervention and the introduction of the New Contract. DESIGN:
      Prospective audit. SETTING: Thirteen general practices (population 68 240).
      METHODS: The case notes of 388 patients receiving treatment for epilepsy were
      reviewed in the two years before, and four years after, the introduction of the
      New Contract in April 2004. An intervention took place, which consisted of (a) a
      letter to each practice summarising the main findings; (b) the provision of a
      comprehensive template; (c) an individualised categorisation for each patient;
      (d) a single educational session led by a Neurologist with an interest in
      epilepsy in March 2004; and (e) the introduction of the New Contract in April
      2004. RESULTS: The audit was completed in 267 cases. There was a significant
      increase in the annual review rate and documentation of seizure frequency. This
      happened after the New Contract was introduced, and has been sustained. The
      number of patients under shared care fell significantly from 22% to 16%. Thirty
      of the 62 (48%) patients with poor control were not receiving shared care. There
      were 13 referrals and 32 practice interventions related to the audit, with 39
      positive outcomes. There was one death in a poorly controlled patient who was not
      under shared care, nor had been seen regularly by their general practitioner.
      CONCLUSION: The unmet needs of some patients were highlighted by the audit
      resulting in appropriate management of these patients. However, despite the
      significantly improved review rates in primary care, and the availability of
      specialist services locally, we remain concerned about the proportion of patients
      with refractory epilepsy who do not seem to be receiving coordinated shared care.

PMID- 21896231
TI  - Persistent non-specific low back pain and patients' experience of general
      practice: a qualitative study.
AB  - AIM: This paper aims to present a conceptual analysis of patients' experience of
      general practice in relation to their persistent non-specific low back pain
      (PLBP). BACKGROUND: PLBP accounts for a considerable amount of the daily workload
      of the general practitioner (GP). GPs need to maintain a good relationship with
      their patient while following guidelines for best practice. The biomedical model
      can contribute to the tensions experienced by a person with PLBP and a shift in
      the prevailing model may facilitate the resolution of these tensions. Qualitative
      research can help clinicians to understand this process and thus facilitate the
      best possible outcome. METHOD: We conducted a series of three in-depth interviews
      over a period of one year with 20 patients with PLBP who had been invited to
      attend a pain management programme. We used the methods of constructivist
      grounded theory to analyse the data. FINDINGS: Several themes emerged that
      provide a deeper understanding of the context in which patient and GP negotiate
      their relationship. Patients describe how they have been fobbed off by a GP who
      is just a general practitioner and not an expert. This allowed patients to
      continue to use the biomedical model; I have something real but the GP lacks
      knowledge. To think that 'nothing can be done', would involve accepting the
      limits of medical knowledge. We also found that over time, as diagnosis and cure
      is not achieved, patient began to question the concept of the medical expert.
      This tension opens up the possibility for a shift away from the biomedical
      towards a biopsychosocial explanatory model.

PMID- 21896232
TI  - Are the NICE guidelines for Obsessive Compulsive Disorder being used in primary
      care?
AB  - This study aims to: 1) assess the proportion of General Practioners (GPs) who are
      aware of or who have read the National Institute for Health and Clinical
      Excellence (NICE; 2005a) guidelines for Obsessive Compulsive Disorder (OCD), 2)
      compare this with the proportion of other mental health disorders found by
      previous research and 3) establish the prevalence of OCD in primary care.
      Questionnaires were sent to all GPs (n = 795) and practice managers (n = 157) in
      Berkshire and Buckinghamshire, South East England. These contained 19 questions
      and took 5 min to complete. After the first set of responses, larger practices
      were visited and telephoned to encourage further responses. The response rates
      were 10.1% from GPs and 19.1% from practice managers. In all, 48.7% of the GPs
      were aware of the NICE guidelines for OCD and 30.3% reported that they had read
      them--higher than for Post-Traumatic Stress Disorder, but lower than for
      depression. Of registered patients, 0.2% were diagnosed with OCD, lower than the
      1.1% found in epidemiological studies.

PMID- 21896233
TI  - Impacts of fast food and the food retail environment on overweight and obesity in
      China: a multilevel latent class cluster approach.
AB  - OBJECTIVE: To simultaneously identify consumer segments based on individual-level
      consumption and community-level food retail environment data and to investigate
      whether the segments are associated with BMI and dietary knowledge in China.
      DESIGN: A multilevel latent class cluster model was applied to identify consumer
      segments based not only on their individual preferences for fast food, salty
      snack foods, and soft drinks and sugared fruit drinks, but also on the food
      retail environment at the community level. SETTING: The data came from the China
      Health and Nutrition Survey (CHNS) conducted in 2006 and two questionnaires for
      adults and communities were used. SUBJECTS: A total sample of 9788 adults living
      in 218 communities participated in the CHNS. RESULTS: We successfully identified
      four consumer segments. These four segments were embedded in two types of food
      retail environment: the saturated food retail environment and the deprived food
      retail environment. A three-factor solution was found for consumers' dietary
      knowledge. The four consumer segments were highly associated with consumers'
      dietary knowledge and a number of sociodemographic variables. CONCLUSIONS: The
      widespread discussion about the relationships between fast-food consumption and
      overweight/obesity is irrelevant for Chinese segments that do not have access to
      fast food. Factors that are most associated with segments with a higher BMI are
      consumers' (incorrect) dietary knowledge, the food retail environment and
      sociodemographics. The results provide valuable insight for policy interventions
      on reducing overweight/obesity in China. This study also indicates that despite
      the breathtaking changes in modern China, the impact of 'obesogenic' environments
      should not be assessed too strictly from a 'Western' perspective.

PMID- 21896234
TI  - Feasibility and effectiveness of supplementation with locally available foods in
      prevention of child malnutrition in Kenya.
AB  - OBJECTIVE: To establish the operational feasibility and effectiveness of using
      locally available foods to prevent malnutrition and improve child growth in
      Kenyan children. DESIGN: Quasi-experimental design with an intervention group of
      children in all villages in one region and a non-intervention group of children
      in all villages in an adjacent region. The intervention was the distribution of a
      monthly food ration for the index child, a separate family ration, and group
      education on appropriate complementary feeding and hygiene. SETTING: Rural
      villages in the arid lands of eastern Kenya with a high prevalence of child
      malnutrition. SUBJECTS: All children in the target villages aged 6-20 months with
      weight-for-length Z-score (WHZ) greater than -2 at baseline. RESULTS: Children in
      the intervention and non-intervention groups had similar baseline anthropometric
      measures. The caregivers in the intervention group confirmed that the intended
      amounts of food supplements were received and child nutrient intake improved.
      During the 7-month intervention period there were significant group differences
      in pre-post Z-score changes between the intervention and non-intervention groups
      for weight-for-age (0.82, P < 0.001) and weight-for-height (1.19, P < 0.001), but
      not for height-for-age (-0.20, P = 0.09), after adjusting for multiple
      covariates. Compared with the non-intervention group, the intervention group had
      a lower prevalence of wasting (0% v. 8.9%, P = 0.0002) and underweight (6.3% v.
      23.0%, P < 0.0001). Infectious morbidity was similar in both groups. CONCLUSIONS:
      The findings suggest that the distribution of locally available foods is
      operationally feasible and improves child weight gain and decreases acute
      malnutrition in Kenyan children.

PMID- 21896235
TI  - Low gene expression of bone morphogenetic protein 7 in brainstem astrocytes in
      major depression.
AB  - The noradrenergic locus coeruleus (LC) is the principal source of brain
      norepinephrine, a neurotransmitter thought to play a major role in the pathology
      of major depressive disorder (MDD) and in the therapeutic action of many
      antidepressant drugs. The goal of this study was to identify potential mediators
      of brain noradrenergic dysfunction in MDD. Bone morphogenetic protein 7 (BMP7), a
      member of the transforming growth factor-beta superfamily, is a critical mediator
      of noradrenergic neuron differentiation during development and has neurotrophic
      and neuroprotective effects on mature catecholaminergic neurons. Real-time PCR of
      reversed transcribed RNA isolated from homogenates of LC tissue from 12 matched
      pairs of MDD subjects and psychiatrically normal control subjects revealed low
      levels of BMP7 gene expression in MDD. No differences in gene expression levels
      of other members of the BMP family were observed in the LC, and BMP7 gene
      expression was normal in the prefrontal cortex and amygdala in MDD subjects.
      Laser capture microdissection of noradrenergic neurons, astrocytes, and
      oligodendrocytes from the LC revealed that BMP7 gene expression was highest in LC
      astrocytes relative to the other cell types, and that the MDD-associated
      reduction in BMP7 gene expression was limited to astrocytes. Rats exposed to
      chronic social defeat exhibited a similar reduction in BMP7 gene expression in
      the LC. BMP7 has unique developmental and trophic actions on catecholamine
      neurons and these findings suggest that reduced astrocyte support for pontine LC
      neurons may contribute to pathology of brain noradrenergic neurons in MDD.

PMID- 21896236
TI  - Meta-analyses of cognitive and motor function in youth aged 16 years and younger
      who subsequently develop schizophrenia.
AB  - BACKGROUND: Previous reviews have reported cognitive and motor deficits in
      childhood and adolescence among individuals who later develop schizophrenia.
      However, these reviews focused exclusively on studies of individuals with
      affected relatives or on population/birth cohorts, incorporated studies with
      estimated measures of pre-morbid intelligence, or included investigations that
      examined symptomatic at-risk participants or participants 18 years or older.
      Thus, it remains unclear whether cognitive and motor deficits constitute robust
      antecedents of schizophrenia. Meta-analyses were conducted on published studies
      that examined cognitive or motor function in youth aged 16 years or younger who
      later developed schizophrenia or a schizophrenia spectrum disorder (SSD) and
      those who did not. METHOD: Twenty-three studies fulfilled the following inclusion
      criteria: (1) written in English; (2) prospective investigations of birth or
      genetic high-risk cohorts, or follow-back investigations of population samples;
      (3) objective measures of cognitive or motor performance at age 16 or younger;
      (4) results provided for individuals who did and who did not develop
      schizophrenia/SSD later in life; and (5) sufficient data to calculate effect
      sizes. Four domains of function were examined: IQ; Motor Function; General
      Academic Achievement; and Mathematics Achievement. RESULTS: Meta-analyses showed
      that, by age 16, individuals who subsequently developed schizophrenia/SSD
      displayed significant deficits in IQ (d=0.51) and motor function (d=0.56), but
      not in general academic achievement (d=0.25) or mathematics achievement (d=0.21).
      Subsidiary analysis indicated that the IQ deficit was present by age 13.
      CONCLUSIONS: These results demonstrate that deficits in IQ and motor performance
      precede the prodrome and the onset of illness.

PMID- 21896237
TI  - The contribution of work and non-work stressors to common mental disorders in the
      2007 Adult Psychiatric Morbidity Survey.
AB  - BACKGROUND: Evidence for an effect of work stressors on common mental disorders
      (CMD) has increased over the past decade. However, studies have not considered
      whether the effects of work stressors on CMD remain after taking co-occurring non
      work stressors into account. METHOD: Data were from the 2007 Adult Psychiatric
      Morbidity Survey, a national population survey of participants 6 years living in
      private households in England. This paper analyses data from employed working age
      participants (N=3383: 1804 males; 1579 females). ICD-10 diagnoses for depressive
      episode, generalized anxiety disorder, obsessive compulsive disorder,
      agoraphobia, social phobia, panic or mixed anxiety and depression in the past
      week were derived using a structured diagnostic interview. Questionnaires
      assessed self-reported work stressors and non-work stressors. RESULTS: The
      effects of work stressors on CMD were not explained by co-existing non-work
      stressors. We found independent effects of work and non-work stressors on CMD.
      Job stress, whether conceptualized as job strain or effort-reward imbalance,
      together with lower levels of social support at work, recent stressful life
      events, domestic violence, caring responsibilities, lower levels of non-work
      social support, debt and poor housing quality were all independently associated
      with CMD. Social support at home and debt did not influence the effect of work
      stressors on CMD. CONCLUSIONS: Non-work stressors do not appear to make people
      more susceptible to work stressors; both contribute to CMD. Tackling workplace
      stress is likely to benefit employee psychological health even if the employee's
      home life is stressful but interventions incorporating non-work stressors may
      also be effective.

PMID- 21896238
TI  - Dissociation mediates the relationship between childhood trauma and hallucination
      proneness.
AB  - BACKGROUND: It has been proposed that the relationship between childhood trauma
      and hallucinations can be explained by dissociative processes. The present study
      examined whether the effect of childhood trauma on hallucination-proneness is
      mediated by dissociative tendencies. In addition, the influence of dissociative
      symptoms on a cognitive process believed to underlie hallucinatory experiences
      (i.e. reality discrimination; the capacity to discriminate between internal and
      external cognitive events) was also investigated. METHOD: Patients with
      schizophrenia spectrum disorders (n=45) and healthy controls (with no history of
      hallucinations; n=20) completed questionnaire measures of hallucination
      proneness, dissociative tendencies and childhood trauma, as well as performing an
      auditory signal detection task. RESULTS: Compared to both healthy and non
      hallucinating clinical controls, hallucinating patients reported both
      significantly higher dissociative tendencies and childhood sexual abuse.
      Dissociation positively mediated the effect of childhood trauma on hallucination
      proneness. This mediational role was particularly robust for sexual abuse over
      other types of trauma. Signal detection abnormalities were evident in
      hallucinating patients and patients with a history of hallucinations, but were
      not associated with pathological dissociative symptoms. CONCLUSIONS: These
      results are consistent with dissociative accounts of the trauma-hallucinations
      link. Dissociation, however, does not affect reality discrimination. Future
      research should examine whether other cognitive processes associated with both
      dissociative states and hallucinations (e.g. deficits in cognitive inhibition)
      may explain the relationship between dissociation and hallucinatory experiences.

PMID- 21896239
TI  - Increased risk of mortality associated with social isolation in older men: only
      when feeling lonely? Results from the Amsterdam Study of the Elderly (AMSTEL).
AB  - BACKGROUND: Loneliness has a significant influence on both physical and mental
      health. Few studies have investigated the possible associations of loneliness
      with mortality risk, impact on men and women and whether this impact concerns the
      situation of being alone (social isolation), experiencing loneliness (feeling
      lonely) or both. The current study investigated whether social isolation and
      feelings of loneliness in older men and women were associated with increased
      mortality risk, controlling for depression and other potentially confounding
      factors. METHOD: In our prospective cohort study of 4004 older persons aged 65-84
      years with a 10-year follow-up of mortality data a Cox proportional hazard
      regression analysis was used to test whether social isolation factors and
      feelings of loneliness predicted an increased risk of mortality, controlling for
      psychiatric disorders and medical conditions, cognitive functioning, functional
      status and sociodemographic factors. RESULTS: At 10 years follow-up,
      significantly more men than women with feelings of loneliness at baseline had
      died. After adjustment for explanatory variables including social isolation, the
      mortality hazard ratio for feelings of loneliness was 1.30 [95% confidence
      interval (CI) 1.04-1.63] in men and 1.04 (95% CI 0.90-1.24) in women. No higher
      risk of mortality was found for social isolation. CONCLUSIONS: Feelings of
      loneliness rather than social isolation factors were found to be a major risk
      factor for increasing mortality in older men. Developing a better understanding
      of the nature of this association may help us to improve quality of life and
      longevity, especially in older men.

PMID- 21896240
TI  - Development and use of EST-SSR markers for assessing genetic diversity in the
      brown planthopper (Nilaparvata lugens Stal).
AB  - To assess genetic diversity in populations of the brown planthopper (Nilaparvata
      lugens Stal) (Homoptera: Delphacidae), we have developed and applied
      microsatellite, or simple sequence repeat (SSR), markers from expressed sequence
      tags (ESTs). We found that the brown planthopper clusters of ESTs were rich in
      SSRs with unique frequencies and distributions of SSR motifs. Three hundred and
      fifty-one EST-SSR markers were developed and yielded clear bands from samples of
      four brown planthopper populations. High cross-species transferability of these
      markers was detected in the closely related planthopper N. muiri. The newly
      developed EST-SSR markers provided sufficient resolution to distinguish within
      and among biotypes. Analyses based on SSR data revealed host resistance-based
      genetic differentiation among different brown planthopper populations; the
      genetic diversity of populations feeding on susceptible rice varieties was lower
      than that of populations feeding on resistant rice varieties. This is the first
      large-scale development of brown planthopper SSR markers, which will be useful
      for future molecular genetics and genomics studies of this serious agricultural
      pest.

PMID- 21896241
TI  - Visual acuity in fish consumers of the Brazilian Amazon: risks and benefits from
      local diet.
AB  - OBJECTIVE: To examine the associations between near and distant visual acuity and
      biomarkers of Hg, Pb, n-3 fatty acids and Se from the local diet of fish-eating
      communities of the Tapajos River in the Brazilian Amazon. DESIGN: Visuo-ocular
      health and biomarkers of Hg (hair, whole blood, plasma), Pb (whole blood), Se
      (whole blood and plasma) and n-3 fatty acids (plasma total phospholipids) were
      assessed in a cross-sectional study. SETTING: Lower Tapajos River Basin (State of
      Para, Brazil), May to July 2006. SUBJECTS: Two hundred and forty-three adults
      (>=15 years) without diagnosed age-related cataracts or ocular pathologies.
      RESULTS: Near visual acuity was negatively associated with hair Hg and positively
      associated with %DHA, with a highly significant Log Hg * age interaction term.
      Stratifying for age showed that while young people presented good acuity, for
      those aged >=40 years, clinical presbyopia was associated with hair Hg >= 15
      MUg/g (OR = 3.93, 95% CI 1.25, 14.18) and %DHA (OR = 0.37, 95% CI 0.11, 1.11). A
      similar age-related pattern was observed for distant visual acuity in relation to
      blood Pb, but the evidence was weaker. CONCLUSIONS: These findings suggest that
      Hg and Pb may affect visual acuity in older persons, while DHA appears to be
      protective for near visual acuity loss. In this population, with little access to
      eye care, diet may have an important influence on visuo-ocular ageing.

PMID- 21896242
TI  - The role of glutathione S-transferase M1 and T1 gene polymorphisms and fruit and
      vegetable consumption in antioxidant parameters in healthy subjects.
AB  - The correlation of glutathione S-transferase (GST) M1/T1 genetic polymorphisms
      with oxidative stress-related chronic diseases was proved recently. The aim of
      the present study was to investigate the association of GSTM1/T1 genetic
      polymorphisms with antioxidant biomarkers and consumption of fruits and
      vegetables (F&V) in healthy subjects. In this study, for conducting a 3 d dietary
      survey, 190 healthy adults were recruited. After DNA extraction, a multiple PCR
      method was used for GSTM1/T1 genotyping. A spectrophotometer method was applied
      for the determination of plasma total antioxidant capacity (T-AOC), vitamin C
      level and erythrocyte GST enzyme activity. A general linear model was used to
      compare the mean values of antioxidant parameters for different GSTM1/T1
      genotypes and consumption of F&V. Polymorphisms of GSTM1/T1 had no effects on
      plasma T-AOC and vitamin C levels. Deletion of the GSTM1 gene decreased the
      erythrocyte GST activity. There was correlation between plasma T-AOC and
      consumption of F&V in the GSTM1- or GSTT1+ subjects. A similar pattern was
      evident for erythrocyte GST activity in the GSTM1- subjects. No association was
      found among consumption of F&V and GSTM1/T1 genotypes and plasma vitamin C level.
      Different consumption of F&V had no impact on plasma T-AOC and vitamin C levels
      in the GSTM1-/GSTT1+ or GSTM1-/GSTT1- subjects. The erythrocyte GST activity was
      more sensitive to consumption of F&V in the individuals with the GSTM1-/GSTT1+
      genotype. Association was found among GSTM1/T1 genotypes, antioxidant parameters
      and consumption of F&V. Large-scale and multiple ethnic studies are needed to
      further evaluate the relationship.

PMID- 21896243
TI  - Plasma appearance and disappearance of an oral dose of 25-hydroxyvitamin D2 in
      healthy adults.
AB  - 25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for
      investigating vitamin D metabolism and requirements. We performed a pilot study
      to assess the approach and practical feasibility of measuring 25(OH)D half-life
      after an oral dose. A total of twelve healthy Gambian men aged 18-23 years were
      divided into two groups to investigate the rate and timing of (1) absorption and
      (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D2. Fasting blood
      samples were collected at baseline and, in the first group, every 2 h post-dose
      for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples
      were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for
      2 h after the first morning void at baseline and on day 15. 25(OH)D2 plasma
      concentration was measured by ultra-performance liquid chromatography-tandem
      MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism
      were measured at baseline and on day 15. The peak plasma concentration of
      25(OH)D2 was 9.6 (sd 0.9) nmol/l at 4.4 (sd 1.8) h. The terminal slope of
      25(OH)D2 disappearance was identified to commence from day 6. The terminal half
      life of plasma 25(OH)D2 was 13.4 (sd 2.7) d. There were no significant
      differences in plasma 25(OH)D3, total 1,25(OH)2D, parathyroid hormone, P, Ca and
      ionised Ca and urinary Ca and P between baseline and day 15 and between the two
      groups. The present study provides data on the plasma response to oral 25(OH)D2
      that will underpin and contribute to the further development of studies to
      investigate 25(OH)D half-life.

PMID- 21896244
TI  - Toward evidence-based, client-centred nutrition education guidelines: dietitian
      and consumer survey results.
AB  - PURPOSE: Dietitian and consumer perspectives on nutrition education needs and
      preferences were explored, as these relate to health status METHODS: Phases 1 and
      2 of a three-phase, mixed-methods study are reported. Phase 1 was a national
      online survey of dietitians, which was designed to inform the development of a
      consumer survey (Phase 2). Consumers responded to an online survey about their
      demographics, medical conditions, and nutrition education needs (what they wanted
      to learn) and preferences (how they wanted to learn). Phase 3 involved
      teleconferenced discussion groups with dietitians across Canada to develop
      guidelines for nutrition education. RESULTS: Dietitian respondents (n=441)
      perceived that consumer health status was important in predicting needs and
      preferences for nutrition education; emotional support was considered most
      important for consumers with life-altering medical conditions. Consumers (n=680)
      expressed interest in an array of nutrition education approaches; cooking tips,
      recipes, and supplement advice were the most popular. Respondents with and
      without medical conditions had similar nutrition education needs and preferences.
      CONCLUSIONS: Because of the complexity of nutrition education and consumers'
      preference for a spectrum of approaches and delivery methods, evidence-based
      nutrition education guidelines are important to inform dietetics training for the
      provision of client-centred nutrition education.

PMID- 21896245
TI  - Environmentally friendly health care food services: a survey of beliefs,
      behaviours, and attitudes.
AB  - PURPOSE: There is increasing global interest in sustainability and the
      environment. A hospital/health care food service facility consumes large amounts
      of resources; therefore, efficiencies in operation can address sustainability.
      Beliefs, attitudes, and behaviours about environmentally friendly practices in
      hospital/health care food services were explored in this study. METHODS:
      Questionnaires addressed environmentally friendly initiatives in building and
      equipment, waste management, food, and non-food procurement issues. The 68
      participants included hospital food service managers, clinical dietitians,
      dietary aides, food technicians, and senior management. Data analysis included
      correlation analysis and descriptive statistics. RESULTS: Average scores for
      beliefs were high in building and equipment (90%), waste management (94%), and
      non-food procurement (87%), and lower in food-related initiatives (61%) such as
      buying locally, buying organic foods, buying sustainable fish products, and
      reducing animal proteins. Average positive scores for behaviours were positively
      correlated with beliefs (waste management, p=0.001; food, p=0.000; non-food
      procurement, p=0.002). Average positive scores for attitude in terms of
      implementing the initiatives in health care were 74% for building and equipment,
      81% for waste management, 70% for non-food procurement, and 36% for food.
      CONCLUSIONS: The difference in food-related beliefs, behaviours, and attitudes
      suggests the need for education on environmental impacts of food choices.
      Research is recommended to determine facilitators and barriers to the
      implementation of green strategies in health care. As food experts, dietitians
      can lead changes in education, practice, and policy development.

PMID- 21896246
TI  - Food management behaviours in food-insecure, lone mother-led families.
AB  - PURPOSE: Little is known about how food is managed in households where food
      resources are scarce. In this study, the household food management behaviours
      utilized by food-insecure, lone mother-led families from Atlantic Canada were
      characterized, and relationships among these behaviours and diet quality were
      examined. METHODS: Thematic analysis of 24 in-depth interviews from a larger
      study of mother-led, low-income families was integrated with sociodemographic
      characteristics, food-insecurity status, and four weekly 24-hour dietary recalls
      for all household members to yield a family behaviour score (FBS) as a summative
      measure of food management behaviours, and a healthy plate score (HPS) as a
      measure of diet quality. RESULTS: Five distinct food management behaviours were
      identified: authoritative, healthism, sharing, structured, and planning
      behaviours. An increase in the FBS was associated with a proportional increase in
      the HPS. Authoritative, healthism, and planning food management behaviours were
      the strongest predictors of the HPS for all household members (p<0.05). The
      structured management behaviour was related to the degree of food insecurity.
      CONCLUSIONS: The FBS and HPS tools hold promise as a way to identify food
      insecure families at risk of low diet quality. The next phase of this research
      will validate the use of these tools in the practice setting.

PMID- 21896247
TI  - Dietitian preceptor knowledge, skills, attitudes, and training: key informant
      perceptions.
AB  - PURPOSE: Through consultation with Canadian dietitian informants, we aimed to
      identify the desired knowledge, skills, and attitudes (KSA) for preceptors,
      training opportunities, and the barriers that prevent preceptor training.
      METHODS: In this qualitative study, an open-ended survey was sent electronically
      to 100 key informants across Canada. Informants had experience as preceptors or
      with dietitian preceptors. Informants were asked to reflect upon the desired KSA,
      training needs, and barriers to training for dietitian preceptors. Categories of
      responses under each of these headings were developed on the basis of informants'
      responses. RESULTS: Forty-nine key informants completed the survey, for a 49%
      response rate. Of the respondents, 41% (20/49) were in clinical practice and 35%
      (17/49) worked in community/public health areas. The knowledge and skills domains
      consisted of themes related to teaching and learning, including assessing,
      planning, and evaluating. Attitudes expressed included considering learners as
      colleagues and the training of learners as a professional responsibility.
      Perceived barriers to training preceptors included workload demands and a lack of
      recognition from peers and employers for this work. Dietitian preceptor training
      opportunities ranged from no training to formal programs. CONCLUSIONS: These
      findings are integral to the basic understanding of the desired KSA and training
      needs of Canadian dietitian preceptors.

PMID- 21896248
TI  - Clustering of specific health-related behaviours among Toronto adolescents.
AB  - PURPOSE: The clustering of specific health-related behaviours was examined among
      adolescents. METHODS: In 2005, cluster analysis was conducted to identify
      homogeneous groups of Toronto, Ontario, 14- to 17-year-old adolescents (n=445)
      with similar behaviour patterns according to self-reported measures of moderate
      to vigorous physical activity (metabolic equivalent [MET] hours a week of MVPA),
      sedentary behaviours (viewing television or videos, using a computer/the
      internet, doing homework, and talking with friends), fruit and vegetable
      consumption, and alcohol consumption. RESULTS: Three clusters of adolescents were
      identified: "active, high screen-time users," "active, low screen-time users,"
      and "less active, least frequent drinkers." CONCLUSIONS: Identifying clusters of
      adolescents with similar health-related behaviour patterns suggests that
      researchers and practitioners should develop and implement interventions tailored
      to specific clusters.

PMID- 21896249
TI  - Dietary patterns in an ethnoculturally diverse population of young Canadian
      adults.
AB  - PURPOSE: Dietary patterns of food consumption were investigated among young urban
      Toronto adults, including men and women from different ethnocultural groups.
      METHODS: We performed a cross-sectional analysis among 1153 adults aged 20 to 29
      years, from the Toronto Nutrigenomics and Health Study. Principal components
      analysis of food intake scores was used to identify food consumption patterns.
      Logistic regression, analysis of variance, and t-tests were used to test for
      differences in dietary patterns between ethnocultural groups and between men and
      women. Partial correlations were used to investigate the relationship between
      patterns and nutrient intake. RESULTS: Three predominant patterns were identified
      and termed "prudent," "Western," and "Eastern" patterns. Caucasians had
      significantly higher prudent pattern scores than did Asians and South Asians,
      while Asians had significantly higher Eastern pattern scores than did other
      ethnocultural groups (p<0.01). Women had higher prudent pattern scores (odds
      ratio [OR]=4.31, 95% confidence interval [CI]=3.11-5.96) and lower Western
      pattern scores (OR=0.62, 95% CI=0.45-0.84) than did men. Dietary pattern scores
      were correlated with nutrient and energy intakes. CONCLUSIONS: We observed
      distinct dietary patterns in this population of young adults. These dietary
      patterns varied significantly between ethnocultural groups and between men and
      women. The patterns were associated with nutrient intake levels; this association
      may have important public health implications.

PMID- 21896250
TI  - Complexity of food preparation and food security status in low-income young
      women.
AB  - PURPOSE: This study was conducted to explore whether preparing more complex meals
      was associated with higher food security status. METHODS: This mixed-methods,
      community-based study involved the use of semistructured interviews to examine
      the cooking practices of a group of young, low-income women in Montreal. Fifty
      participants aged 18 to 35 were recruited at 10 locations in five low-income
      neighbourhoods. Food security status was the main outcome measure and the main
      exposure variable, "complex food preparation," combined the preparation of three
      specific food types (soups, sauces, and baked goods) using basic ingredients.
      RESULTS: Low-income women preparing a variety of meals using basic ingredients at
      least three times a week were more than twice as likely to be food secure as were
      women preparing more complex meals less frequently. CONCLUSIONS: Women who
      prepared more complex meals more frequently had higher food security. Whether
      this means that preparing more complex foods results in greater food security
      remains unclear, as this was an exploratory study.

PMID- 21896251
TI  - Alberta Nutrition Guidelines for Children and Youth: awareness and use in
      schools.
AB  - PURPOSE: In June 2008, the Alberta government released the Alberta Nutrition
      Guidelines for Children and Youth. We evaluated the awareness of and intent to
      use the guidelines in Alberta schools, and sought to determine whether
      organizational characteristics were a factor in adoption of the guidelines.
      METHODS: Randomly selected schools from across Alberta completed a 19-question
      telephone survey, which included open- and closed-ended questions about the
      schools' characteristics, the priority given to healthy eating, awareness of the
      guidelines, and the schools' intent to use the guidelines. Of the 554 schools
      contacted, 357 (64%) completed the survey. RESULTS: Overall, 76.1% of schools
      were aware of the guidelines and 65% were in the process of adopting them. Fifty
      percent of schools identified healthy eating as a high priority and 65.9%
      reported making changes to improve the nutritional quality of foods offered in
      the past year. Schools that were larger, public, and urban, and had a school
      champion and healthy eating as a high priority were more likely to be adopting
      the guidelines. CONCLUSIONS: Most schools were aware of the nutrition guidelines
      and many had begun the adoption process. Identifying a school champion may be an
      important first step for schools in terms of adopting health promotion
      initiatives.

PMID- 21896252
TI  - Nutritional analysis of a long-term care menu before and after an increase in the
      raw food cost allowance.
AB  - PURPOSE: Regular, nontherapeutic menus were compared before and after an increase
      in the Ontario long-term care (LTC) raw food cost allowance (RFCA). The purpose
      was to determine whether any significant nutritional differences existed between
      the old and new menus and whether they met target values for adequacy, according
      to the Dietary Reference Intake (DRI) nutrient recommendations or other target
      values relevant to Ministry of Health and Long-Term Care standards. METHODS: A
      southeastern Ontario LTC facility fall/winter 2006/2007 menu and fall/winter
      2007/2008 menu were used for nutrient analysis with ESHA Food Processor SQL
      10.1.0. Each menu was compared with target values based on Canada's Food Guide
      (CFG) for 1992 and 2007, and with DRI nutrient recommendations. RESULTS: The
      2007/2008 menu provided significantly more servings of vegetables and fruit,
      meeting the 2007 CFG recommendations, and significantly greater amounts of some
      nutrients (e.g., vitamin C, protein, magnesium, potassium, fibre, and total
      water). It also came closer to meeting DRI target recommendations. CONCLUSIONS:
      While some improvements have been made to the menu in this specific facility,
      further improvements, possibly through supplementation, must be made to ensure
      nutritional adequacy for all residents.

PMID- 21896253
TI  - The times they are a-changin'.
AB  - Change is the one constant in a constantly changing world, including the world of
      dietetic practice. Over a 40-year career, I have witnessed and participated in
      many such changes. Key lessons from my early career with Manitoba Agriculture and
      Manitoba Health include an understanding of the power of teamwork, of the
      importance of communication skills, of the need for shared knowledge and
      expertise, and of ways to connect nutrition messages with food and eating. Later,
      my work as director of education in a family medicine residency program taught me
      the value of building a portfolio of knowledge and skills and of working with
      families. Similarly, my work with the Organization for Cooperation in Overseas
      Development led me to appreciate the need for cultural sensitivity in our work.
      Opportunities with Dietitians of Canada have shown me that future directions must
      include continued interdisciplinary development of policy and position papers.
      Other important challenges include determining issues relevant to various areas
      of dietetic practice, working to achieve Vision 2020 goals, and inspiring and
      nurturing new leadership among younger Dietitians of Canada members.

PMID- 21896254
TI  - Editorial Issue 3 2011: four planning challenges from diverse research studies.

PMID- 21896255
TI  - Invisible populations: parallels between the health of people with intellectual
      disability and people of a refugee background.
AB  - When considering the delivery of primary health care in the community, some
      populations remain virtually invisible. While people with intellectual disability
      might seem to share few characteristics with refugees and humanitarian entrants,
      there are a number of difficulties that both groups share when accessing and
      receiving primary health care. Commonalities include communication barriers,
      difficulties accessing past medical records and the complexity of health needs
      that confront the practitioner providing health care. These issues and additional
      systemic barriers that prevent the delivery of optimal health care to both groups
      are explored. Integrated multidisciplinary care is often required for the
      delivery of best practice care; however, such care can be difficult for each
      group to access. In May 2010, the specific Medicare Health Assessment Item
      numbers for both of these groups were incorporated into a group of more generic
      Item numbers. This has resulted in a lost opportunity to enhance the evidence
      surrounding health care delivery to these vulnerable populations. This paper
      recognises the importance of health policy in leading affirmative action to
      ensure these populations become visible in the implementation of the National
      Primary Health Care Strategy.

PMID- 21896256
TI  - Working together as a catalyst for change: the development of a peer mentoring
      model for the prevention of chronic disease in Australian Indigenous communities.
AB  - This paper outlines the development of a model for an Indigenous peer mentoring
      program. The aim of this program is to improve the health of Indigenous people
      living in the western suburbs of Melbourne, Australia. Although the benefits of
      peer mentoring are well documented, particularly in relation to disease
      prevention, little has been written about the specific benefits for Indigenous
      people. While developing this model, it became apparent that to be successful,
      peer mentoring programs for Indigenous people need to be flexible, informal and
      draw on the knowledge and skills of the local community in partnership with local
      services.

PMID- 21896257
TI  - Mental health and barriers to the achievement of the 'right to health'.
AB  - This paper explores issues relating to access to physical and mental health care
      for people with mental health problems in light of Australia's endorsement in
      2008 of the Convention of the Rights of Persons with Disabilities, which
      established the right to health and to health care. Interviews were conducted
      with 10 key stakeholders with legal, policy, clinical and advocacy roles within
      South Australia and at a national and international level. Participants
      identified several barriers to the achievement of the right to health for people
      with mental illness, with discussion highlighting the legal definition of rights,
      governance of health and mental health, and structural barriers to receipt of
      care as the primary barriers. The data are explored in relation to social models
      of disability.

PMID- 21896258
TI  - The work, education and career pathways of nurses in Australian general practice.
AB  - There is little understanding about the educational levels and career pathways of
      the primary care nursing workforce in Australia. This article reports on survey
      research conducted to examine the qualifications and educational preparation of
      primary care nurses in general practice, their current enrolments in education
      programs, and their perspectives about post-registration education. Fifty-eight
      practice nurses from across Australia completed the survey. Over 94% reported
      that they had access to educational opportunities but identified a range of
      barriers to undertaking further education. Although 41% of nurses said they were
      practising at a specialty advanced level, this correlated with the number of
      years they had worked in general practice rather than to any other factor,
      including level of education. Respondents felt a strong sense of being regarded
      as less important than nurses working in the acute care sector. Almost 85% of
      respondents reported that they did not have a career pathway in their
      organisation. They also felt that while the public had confidence in them, there
      was some way to go regarding role recognition.

PMID- 21896259
TI  - Risk factors for glaucoma: what do they really mean?
AB  - Glaucoma is an insidious eye disease, potentially putting 4% of older Australians
      at risk of blindness, unless detected sufficiently early for initiation of
      effective treatment. This paper reports on the strengths of evidence and glaucoma
      risk factors that can be identified by primary health care providers from a
      patient's history. A comprehensive search of peer-reviewed databases identified
      relevant secondary evidence published between 2002 and 2007. Risk factors that
      could be determined from a patient's history were identified. A novel glaucoma
      risk factor reference guide was constructed according to evidence strength and
      level of concern regarding risk of developing glaucoma. The evidence is strong
      and consistent regarding the risk of developing glaucoma, and elevated
      intraocular pressure, advancing age, non-Caucasian ethnicity and family history
      of glaucoma. There is moderate evidence of association with glaucoma, and
      migraine, eye injury, myopia and long-term use of corticosteroids. There is
      conflicting evidence for living in a rural location, high blood pressure,
      diabetes and smoking. Early detection of people at risk of developing glaucoma
      can be initiated using our risk factor guide coupled with a comprehensive patient
      history. Timely future assessment and subsequent management strategies for at
      risk individuals can then be effectively and efficiently actioned.

PMID- 21896260
TI  - Why do we not use trained interpreters for all patients with limited English
      proficiency? Is there a place for using family members?
AB  - Australia and New Zealand both have large populations of people with limited
      English proficiency (LEP). Australia's free telephone interpreter service, which
      is also used by New Zealand through Language Line (LL) but at a cost to the
      practices, is underused in both countries. Interpreter guidelines warn against
      the use of family members, yet the lack of uptake of interpreter services must
      mean that they are still often used. This paper reviews the literature on medical
      interpreter use and reports the results of a week-long audit of interpreted
      consultations in an urban New Zealand primary health centre with a high
      proportion of refugee and migrant patients. The centre's (annualised) tally of
      professionally interpreted consultations was three times more than that of LL
      consultations by all other NZ practices put together. Despite this relatively
      high usage, 49% of all interpreted consultations used untrained interpreters
      (mostly family), with more used in 'on-the-day' (OTD) clinics. Clinicians rated
      such interpreters as working well 88% of the time in the OTD consultations, and
      36% of the time in booked consultations. An in-house interpreter (28% of
      consultations) was rated as working well 100% of the time. Telephone interpreters
      (21% of consultations) received mixed ratings. The use of trained interpreters is
      woefully inadequate and needs to be vigorously promoted. In primary care settings
      where on-going relationships, continuity and trust are important - the ideal
      option (often not possible) is an in-house trained interpreter. The complexity of
      interpreted consultations needs to be appreciated in making good judgements when
      choosing the best option to optimise communication and in assessing when there
      may be a place for family interpreting. This paper examines the elements of
      making such a judgement.

PMID- 21896261
TI  - Satisfaction with referral relationships between general practice and allied
      health professionals in Australian primary health care.
AB  - Chronic diseases require a multidisciplinary approach to provide patients with
      optimal care in general practice. This often involves general practitioners (GPs)
      referring their patients to allied health professionals (AHPs). The Team-link
      study explored the impact of an intervention to enhance working relationships
      between GPs and AHPs in general practice regarding the management of two chronic
      diseases: diabetes and ischaemic heart disease (IHD) or hypertension. The Measure
      of Multidisciplinary Linkages (MoML) questionnaire was developed to assess
      professional interactions and satisfaction with various aspects of the
      multidisciplinary relationship. Questionnaires were completed at baseline and 6
      months by GPs (n=29) participating in the Team-link project and by AHPs (n=39)
      who had a current working relationship with these GPs. The Chronic Care Team
      Profile (CCTP) and Clinical Linkages Questionnaire (CLQ) were also completed by
      GPs. There were significant changes from baseline to 6 months after the
      intervention measures for individual items and overall MoML scores for GPs,
      especially items assessing 'contact', 'shared care' and 'satisfaction with
      communication'. The comparable item in the CLQ, 'Shared Care', also showed
      significant improvement. However, there were no statistically significant
      correlations between the change in overall 'Referral Satisfaction' scores in the
      GP MoML and the CLQ. The CCTP also improved and was a weak negative correlation
      between the GP MoML and two of the subscores of this instrument. There were no
      changes in AHP measure. This study demonstrates that the instrument is sensitive
      to differences between providers and conditions and is sensitive to change over
      time following an intervention. There were few associations with the other
      measures suggesting that the MoML might assess other aspects of teamwork
      involving practitioners who are not collocated or in the same organisation.

PMID- 21896262
TI  - Primary health care service delivery networks for the prevention and management
      of type 2 diabetes: using social network methods to describe interorganisational
      collaboration in a rural setting.
AB  - Adults with type 2 diabetes or with behavioural risk factors require
      comprehensive and well coordinated responses from a range of health care
      providers who often work in different organisational settings. This study
      examines three types of collaborative links between organisations involved in a
      rural setting. Social network methods were employed using survey data on three
      types of links, and data was collected from a purposive sample of 17
      organisations representing the major provider types. The analysis included a mix
      of unconfirmed and confirmed links, and network measures. General practices were
      the most influential provider group in initiating referrals, and they referred to
      the broadest range of organisations in the network. Team care arrangements formed
      a small part of the general practice referral network. They were used more for
      access to private sector allied health care providers and less for sharing care
      with public sector health services. Involvement in joint programs/activities was
      limited to public and non-government sector services, with no participation from
      the private sector. The patterns of interactions suggest that informal referral
      networks provide access to services and coordination of care for individual
      patients with diabetes. Two population subgroups would benefit from more
      proactive approaches to ensure equitable access to services and coordination of
      care across organisational boundaries: people with more complex health care needs
      and people at risk of developing diabetes.

PMID- 21896263
TI  - How cardiac patients describe the role of their doctors in smoking cessation: a
      qualitative study.
AB  - This article reports a qualitative study investigating patients' experiences of
      ongoing smoking or smoking cessation after hospitalisation for an acute coronary
      syndrome (myocardial infarction or unstable angina) and describes how study
      participants spoke about the role of their doctors in smoking cessation. We
      invited individuals who had been admitted to an Australian public hospital in
      2005 with a discharge diagnosis of an acute cardiac syndrome and who were smokers
      at the time of their hospitalisation to participate. Participants underwent a
      semi-structured interview and ongoing smokers also completed a 'stages of change'
      questionnaire. In total, 35 participants were interviewed, including 14 who were
      no longer smoking at least 12 months after their admission and 21 who were.
      Findings gave insight into the ways that cardiac patients perceive smoking
      cessation advice from their doctors, the perceived stigma of smoking and how lay
      understandings about smoking and smoking cessation emphasise the role of choice
      and individual responsibility. Our findings also indicate considerable scope for
      GPs and other doctors to offer better smoking cessation support to patients with
      established cardiovascular disease, particularly after a period of
      hospitalisation when the majority are highly motivated to stop smoking.

PMID- 21896264
TI  - Feasibility, acceptability and impact of a telephone support service initiated in
      primary medical care to help Arabic smokers quit.
AB  - Evidence-based tobacco control in ethnic minorities is compromised by the near
      absence of rigorous testing of interventions in either prevention or cessation.
      This randomised controlled trial was designed to evaluate the feasibility,
      acceptability and impact of a culturally specific cessation intervention
      delivered in the context of primary medical care in the most culturally diverse
      region of New South Wales. Adult Arabic smokers were recruited from practices of
      29 general practitioners (GPs) in south-west Sydney and randomly allocated to
      usual care (n=194) or referred to six sessions of smoking cessation telephone
      support delivered by bilingual psychologists (n=213). Although 62.2% of
      participants indicated that telephone support would benefit Arabic smokers, there
      were no significant differences at 6 or 12 months between intervention and
      control groups in point prevalence abstinence rates (11.7% vs 12.9%, P=0.83; 8.4%
      vs 11.3%, P=0.68, respectively) or the mean shift in stage-of-change towards
      intention to quit. As participants and GPs found telephone support acceptable, we
      also discuss redesign and the unfulfilled obligation to expand the evidence base
      in tobacco control from which the ethnic majority already benefits.

PMID- 21896265
TI  - General practitioner attitudes to prescribing hepatitis C antiviral therapy in a
      community setting.
AB  - There is a growing debate about the prescription of hepatitis C virus (HCV)
      antiviral therapies within a community setting in Australia. This study aimed to
      identify interest and confidence among general practitioners (GPs) in prescribing
      HCV antiviral therapy in a community setting. Data from 580 GPs who responded to
      a cross-sectional population-based survey were analysed to measure: self-reported
      interest and confidence in initiating HCV antiviral therapy; and/or prescribing
      maintenance antiviral therapy; and self-perceived education needs about HCV
      antiviral therapy. Forty-two percent of respondents indicated they would be
      interested in prescribing HCV antiviral therapy. Most were not confident to
      initiate therapy (80%). Higher proportions indicated that they would be more
      confident in prescribing maintenance therapy (35%) rather than initiating (7%)
      therapy (z=10.5, P<0.001). Confidence in prescribing was related to a higher
      caseload of patients with HCV (P=0.001) and being a HIV community-based
      prescriber (P=0.002). Fifty-three percent of respondents expressed an interest in
      education about HCV antiviral therapy. The initial step to recruit potential
      primary care prescribers of HCV antiviral therapies should be to develop an
      integrated education program. Recruitment to this program might be most efficient
      from GPs with a high caseload of patients with HCV.

PMID- 21896266
TI  - A snapshot of general practitioner attitudes, levels of confidence and self
      reported paediatric asthma management practice.
AB  - The prevalence of asthma in Australia is high. Previous findings have suggested
      that asthma management, particularly in primary care, remains suboptimal and
      recent government initiatives to improve asthma management and encourage the use
      of written asthma action plans (WAAPs) in general practice have been implemented.
      We aimed to assess the attitudes, confidence and self-reported paediatric asthma
      management practices of a convenience sample of Australian general practitioners
      (GPs). A baseline questionnaire was administered to GPs as part of a randomised
      controlled trial. General practitioners (GPs) were recruited from two areas of
      greater metropolitan Sydney, NSW between 2006 and 2008. Invitations were sent to
      an estimated 1200 potentially eligible GPs. Of 150 (12.5%) GPs that enrolled, 122
      (10.2%) completed the baseline questionnaire. Though 89% were aware of the
      Australian National Asthma Guidelines, less than 40% were familiar with guideline
      recommendations. While 85.2% had positive attitudes towards WAAPs, only 45.1%
      reported providing them frequently. For children with frequent symptoms, 90%
      agreed they should prescribe daily, inhaled corticosteroids (ICS), and 83%
      reported currently prescribing ICS to such patients. These findings indicate gaps
      between GP attitudes and behaviours and highlights opportunities for
      interventions to improve paediatric asthma management.

PMID- 21896267
TI  - Efficacy of parasitological methods for the diagnosis of Strongyloides
      stercoralis and hookworm in faecal specimens.
AB  - To compare the efficacy of stool examination for the detection of Strongyloides
      stercoralis and hookworm, a total of 634 stool samples from the routine
      laboratory service of the Pharmacia Faculty, Federal University of Bahia, Brazil,
      were examined by agar plate culture (APC), Baermann-Moraes and spontaneous
      sedimentation. The sensitivity of agar plate culture, calculated by combining
      results of all 3 methods, was 95% for S. stercoralis and 77.6% for hookwoorm.
      Moreover, APC had superior accuracy than Baermann-Moraes and spontaneous
      sedimentation for S. stercoralis and hookworm diagnosis, respectively. The S.
      stercoralis and hookworm positive samples from the laboratory routine, obtained
      after the previous analysis, along with those initially selected, were used to
      evaluate the concordance between microscopic examination and both the type of
      furrows left by larvae and the time for culture positivity using the APC method.
      Of 115 stool samples positive for S. stercoralis and 92 positive for hookworm,
      110 (95.7%) and 89 (96.7%), respectively, had concordant results for furrows and
      morphological characteristics. The cumulative percentage of positivity increased
      to 94% by the third day of observation; at this time, only 19.6% of hookworm
      positive samples had positive culture plates. Analyses of 74 S. stercoralis
      positive stool samples stored at 4 degrees C for 24, 48 and 72h showed the
      presence of larvae in 48.6%, 28.4% and 23% of samples, respectively when re
      examined by the APC. As a definitive diagnosis of strongyloidiasis depends on the
      microscopic demonstration of parasites, increasing the sensitivity of the
      detection requires the use of different parasitological methods, including APC.

PMID- 21896269
TI  - Comparative study of entero-parasitic infections among HIV sero-positive and sero
      negative patients in Lagos, Nigeria.
AB  - BACKGROUND: Intestinal parasites are endemic in many parts of the world where HIV
      infection is also widespread. Previous studies had shown that the spectrum of
      opportunistic and common endemic parasitic infections with HIV vary in different
      regions and usually reflect the infections prevalent in these regions. This
      present study was aimed at comparing the prevalence and types of intestinal
      parasitic infections in HIV sero-positive and sero-negative patients in Lagos.
      MATERIALS AND METHODS: Venous blood and stool samples of 1080 patients, recruited
      from three health care institutions were screened for HIV infection and
      intestinal parasites using HIV-1, HIV-2 rapid tests, direct wet mount with
      saline/iodine and formol-ether technique, respectively. RESULTS: Results showed
      that 6% (65/1080) of patients were sero-positive for HIV infection. In addition,
      23.3% (252/1080) patients were infected with intestinal parasites and 33.8%
      (22/65) of patients with HIV had intestinal parasites co-infections. The
      prevalence of Entamoeba histolytica/Entamoeba dispar, Entamoeba coli, Iodamoeba
      butschilii, Giardia intestinalis, and Hookworm were statistically significantly
      higher among HIV sero-positive patients as compared to the HIV sero-negative
      patients. In addition, HIV sero-positive patients had higher odds of mixed
      intestinal parasites than the HIV sero-negative patients (9.1% versus 3.9%;
      adjusted OR 2.05, 95% CI, 1.14-3.72, P=0.021). CONCLUSION: In this study
      population, HIV sero-positive patients were more likely to have intestinal
      parasitic infections. The study underscores the public health significance of
      intestinal parasitic infections in HIV infected individuals.

PMID- 21896268
TI  - Research challenges and gaps in malaria knowledge in Papua New Guinea.
AB  - Taking into consideration the relative number of people living in Papua New
      Guinea the burden of malaria in this country is among the highest in Asia and the
      Pacific region. This article summarizes the research questions and challenges
      being undertaken by the Southwest Pacific International Center of Excellence for
      Malaria Research in the context of the epidemiology, transmission and
      pathogenesis of Plasmodium falciparum and P. vivax at the present time and the
      recent past. It is hoped that the research accomplished and local infrastructure
      strengthened by this effort will help inform regional and national policy with
      regard to the control and ultimately elimination of malaria in this region of the
      world.

PMID- 21896270
TI  - Effects of hydrostatic pressure on the quaternary structure and enzymatic
      activity of a large peptidase complex from Pyrococcus horikoshii.
AB  - While molecular adaptation to high temperature has been extensively studied, the
      effect of hydrostatic pressure on protein structure and enzymatic activity is
      still poorly understood. We have studied the influence of pressure on both the
      quaternary structure and enzymatic activity of the dodecameric TET3 peptidase
      from Pyrococcus horikoshii. Small angle X-ray scattering (SAXS) revealed a high
      robustness of the oligomer under high pressure of up to 300 MPa at 25 degrees C
      as well as at 90 degrees C. The enzymatic activity of TET3 was enhanced by
      pressure up to 180 MPa. From the pressure behavior of the different rate
      constants we have determined the volume changes associated with substrate binding
      and catalysis. Based on these results we propose that a change in the rate
      limiting step occurs around 180 MPa.

PMID- 21896271
TI  - Production of channel catfish with sperm cryopreserved by rapid non-equilibrium
      cooling.
AB  - This report describes the feasibility of using vitrification for fish sperm.
      Vitrification can be used to preserve samples in the field and offers an
      alternative to conventional cryopreservation, although it has not been
      systematically studied for sperm of aquatic species. The overall goal of the
      project was to develop streamlined protocols that could be integrated into a
      standardized approach for vitrification of aquatic species germplasm. The
      objectives of the present study in channel catfish (Ictalurus punctatus) were to:
      (1) evaluate the acute toxicity of 5%, 10%, 20% and 30% methanol, N,N-dimethyl
      acetamide, dimethyl sulfoxide, 1,2-propanediol, and methyl glycol; (2) evaluate a
      range of devices commonly used for cryopreservation and vitrification of
      mammalian sperm; (3) compare vitrification with and without cryoprotectants; (4)
      evaluate the post-thaw membrane integrity of sperm vitrified in different
      cryoprotectant solutions, and (5) evaluate the ability of vitrified sperm to
      fertilize eggs. Cryoprotectant concentrations of higher than 20% were found to be
      toxic to sperm. Methanol and methyl glycol were the least toxic at a
      concentration of 20% with an exposure time of less than 5 min. We evaluated a
      method reported for human sperm, using small volumes in loops (15 MUl) or cut
      standard straws (20 MUl) with and without cryoprotectants plunged into liquid
      nitrogen. Cryoprotectant-free vitrification using loops did not yield
      fertilization (assessed by neurulation), and the fertilization rates observed in
      two trials using the cut standard straws were low (~2%). In general,
      fertilization values for vitrification experiments were low and the use of low
      concentrations of cryoprotectants yielded lower fertilization (<10%) than the use
      of vitrification solutions containing high cryoprotectant concentrations (as high
      as 25%). The highest neurulation obtained was from a mixture of three
      cryoprotectants (20% methanol+10% methyl glycol+10% propanediol) with a single
      step addition. This was reflected in the flow cytometry data from which the
      highest membrane integrity using loops was for 20% methanol+10% methyl glycol+10%
      propanediol (~50%). We report the first successful sperm vitrification in fish
      and production of offspring from vitrified sperm in channel catfish. Although the
      fertilization values were low, at present this technique could nevertheless be
      used to reconstitute lines (especially in small aquarium fishes), but it would
      require improvement and scaling up before being useful as a production method for
      large-bodied fishes such as catfish.

PMID- 21896272
TI  - Depletion of optineurin in RGC-5 cells derived from retinal neurons causes
      apoptosis and reduces the secretion of neurotrophins.
AB  - Optineurin is a Golgi complex-associated ubiquitous protein with high expression
      levels in retinal ganglion cells (RGCs). Mutations in optineurin have been
      observed in rare hereditary cases of primary open-angle glaucoma and in
      amyotrophic lateral sclerosis. We explored the possibility that optineurin
      deficiency will compromise neuronal exocytosis leading to a diminished secretion
      of neurotrophic factors that are critically required for neuronal survival. To
      this end, we used RNA interference to induce depletion of optineurin in RGC-5
      cells derived from retinal neurons. SiRNA specific for optineurin was transiently
      transfected. Moreover, a stable cell line with constitutive optineurin deficiency
      (RGC-5 pSilencer OPTN) was generated. In addition, we investigated the
      subcellular localization of optineurin in primary RGCs in retinal cell cultures
      isolated from eyes of mature mice. In RGC-5 cells, optineurin localized to the
      periphery of the Golgi complex and was observed in vesicular structures
      throughout the cytoplasm and close to the plasma membrane. A comparable Golgi
      associated localization of optineurin was observed in cultured primary RGCs that
      were identified by TUJ1 labeling. Optineurin deficiency caused a marked increase
      in the number of RGC-5 cells with fragmented Golgi complex. RGC-5 pSilencer OPTN
      with stable optineurin deficiency showed a pronounced increase in the number of
      cells undergoing apoptotic cell death. Furthermore, the amounts of secreted
      neurotrophin-3 (NT-3) and ciliary neurotrophic factor were significantly lower in
      culture medium of RGC-5 pSilencer OPTN cells when compared to controls. Adding
      exogenous NT-3 to the culture medium to achieve amounts seen in control cultures
      completely prevented the increase in apoptotic cell death. We propose that lack
      of neurotrophic support due to impaired secretion of neurotrophic proteins is a
      critical factor that causes or contributes to RGC or motor neuron death in
      patients with mutated optineurin.

PMID- 21896273
TI  - Signal-peptide-peptidase-like 2a (SPPL2a) is targeted to lysosomes/late endosomes
      by a tyrosine motif in its C-terminal tail.
AB  - Signal-peptide-peptidase-like 2A (SPPL2a), an aspartyl intramembrane protease,
      has been implicated in the proteolysis of TNF-alpha, Fas Ligand and Bri2. Here,
      we show that endogenous SPPL2a - in agreement with overexpression studies - is
      localised in membranes of lysosomes/late endosomes. Furthermore, we have analysed
      the molecular determinants for lysosomal sorting of SPPL2a by creating chimaeric
      constructs between SPPL2a and its plasma membrane localised homologue SPPL2b.
      Lysosomal transport of SPPL2a critically depends on its cytosolic carboxyterminal
      tail. A canonical tyrosine-based sorting motif of the YXXo type at position 498
      is sufficient to direct SPPL2a to lysosomal/late endosomal compartments. This
      motif accounts for the differential localisation of the homologous proteases
      SPPL2a and SPPL2b and thereby influences the access to substrates and biological
      function of SPPL2a.

PMID- 21896274
TI  - Effects of green tea catechins on gramicidin channel function and inferred
      changes in bilayer properties.
AB  - Green tea's health benefits have been attributed to its major polyphenols, the
      catechins: (-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG), (
      )-epigallocatechin (EGC), and epicatechin (EC). Catechins (especially EGCG)
      modulate a wide range of biologically important molecules, including many
      membrane proteins. Yet, little is known about their mechanism(s) of action. We
      tested the catechins' bilayer-modifying potency using gramicidin A (gA) channels
      as molecular force probes. All the catechins alter gA channel function and modify
      bilayer properties, with a 500-fold range in potency (EGCG>ECG?EGC>EC).
      Additionally, the gallate group causes current block, as evident by brief
      downward current transitions (flickers).

PMID- 21896275
TI  - The tumor suppressor p33ING1b upregulates p16INK4a expression and induces
      cellular senescence.
AB  - ING1 protein is a tumor suppressor which plays significant roles in multiple
      cellular activities. p47(ING1a) and p33(ING1b) are major splice isoforms of ING1
      and their roles in senescence need further investigations. Here we studied the
      functions of ING1 isoforms in cellular senescence and gene regulation, with focus
      on p16(INK4a). We observe that p33(ING1b) protein is the major ING1 isoform
      expressed in 2BS human diploid fibroblasts. Overexpression of p33(ING1b) induces
      cellular senescence and upregulates p16(INK4a) expression in 2BS fibroblasts.
      p33(ING1b) upregulates p16(INK4a) transcription. p33(ING1b) and p300 bind to the
      p16(INK4a) promoter. p300/CBP-specific inhibitor curcumin can reverse the
      induction of p16(INK4a) by p33(ING1b). These results help to better understand
      the function of ING1.

PMID- 21896276
TI  - Management of protein intake in the fruit fly Anastrepha fraterculus.
AB  - This work tested if carbohydrates and proteins ingestion is regulated in the
      South American fruit fly, Anastrepha fraterculus, to optimize survival and
      reproduction. Adult food treatments were established by providing sugar and
      hydrolyzed yeast in various combinations either alone or mixed at a standard 3:1
      ratio (sugar:hydrolyzed yeast). Individual food consumption was assessed and
      related to survival patterns. The effects of adult feeding on fecundity and
      fertility patterns were investigated in groups of flies. Sugar consumption was
      the lowest in the treatment where it was provided with hydrolyzed yeast at a
      fixed 3:1 ratio. Consumption of hydrolyzed yeast did not differ between this
      treatment and the one in which this solution was complemented with one solution
      of sugar. It seems that a mixture of sugar and hydrolyzed yeast at a fixed ratio
      of 3:1, respectively, restricts extra ingestion of sugar; most probably because
      of negative response of the fly to overconsumption of protein. Survival was
      affected by the treatments, being lower in those cases where protein was at the
      fixed ratio. Group experiments revealed that protein restriction expanded
      longevity and decreased egg production. In contrast, egg production was enhanced
      when flies were kept continuously with a mixture of yeast and sugar plus an extra
      source of sugar, and this was not in detriment of survival. Our results suggest
      that fixed sugar-protein ratios in which protein is in excess affects fitness
      components such as longevity and reproduction. These findings are discussed from
      a theoretical and applied perspective in the context of pest control by means of
      the sterile insect technique.

PMID- 21896277
TI  - Large interclone differences in melezitose secretion in the facultatively ant
      tended black bean aphid Aphis fabae.
AB  - Many aphids are known to engage in a trophic mutualism with ants, whereby the
      aphids secrete sugary-rich honeydew which is collected by the ants for food, and
      the ants, in exchange, protect the aphids against natural enemies. Previous
      results, however, suggest that the production of some of the honeydew sugars,
      such as the ant-attractant trisaccharide melezitose, may induce an indirect cost
      to the aphids. This led us to believe that large differences in the nature of the
      secreted honeydew might exist, due to some clones capitalizing more or less on
      their mutualistic interaction with ants, or due to some "cheater" clones
      foregoing the production of particular sugars, instead taking advantage of the
      ant-attracting effect of other non sugar-deficient clones, co-occurring on the
      same plant. Here we present data on clonal variation in the composition of
      honeydew of the black bean aphid Aphis fabae which confirm this prediction. In
      particular, our results show that there was large interclone variation in the
      amount of glucose, melezitose and total sugar produced. The variation in the
      production of melezitose, however, showed particularly large differences, with
      54% (7 out of 13) of the clones screened being virtually deficient for the
      production of this sugar, irrespective of whether the aphid colonies were ant
      tended or not. The consequences of this finding in the context of the evolution
      and maintenance of the ant-aphid mutualism, as well as the adaptive benefits of
      oligosaccharide synthesis in aphids and other insects are discussed.

PMID- 21896278
TI  - Metabotropic glutamate receptor 5 antagonist 2-methyl-6-(phenylethynyl)pyridine
      (MPEP) microinfusions into the nucleus accumbens shell or ventral tegmental area
      attenuate the reinforcing effects of nicotine in rats.
AB  - Systemic administration of the mGlu5 receptor antagonist 2-methyl-6
      (phenylethynyl)-pyridine (MPEP) was previously shown to selectively attenuate
      nicotine self-administration without affecting food-maintained responding in
      rats. Glutamatergic neurotransmission in the ventral tegmental area (VTA) and
      nucleus accumbens (NAcc) shell plays an important role in the reinforcing effects
      of nicotine. To determine the brain sites that may mediate the systemic effects
      of MPEP on nicotine self-administration, the present study investigated the
      effects of MPEP microinfusions into the VTA or the NAcc shell on nicotine and
      food self-administration in separate groups of rats. Administration of low MPEP
      doses (0, 0.5, 1, and 2 MUg/0.5 MUl/side) microinfused into the NAcc shell had no
      effect on nicotine self-administration, whereas higher MPEP doses (0, 10, 20, and
      40 MUg/0.5 MUl/side) microinfused into the NAcc shell dose-dependently attenuated
      nicotine self-administration without affecting food-maintained responding.
      Microinfusions of MPEP into the VTA (0, 10, 20, and 40 MUg/0.5 MUl/side)
      significantly decreased both nicotine and food self-administration at 20 MUg/0.5
      MUl/side but did not affect responding for either reinforcer at 40MUg/0.5
      MUl/side. This lack of effect of 40 MUg/0.5 MUl/side MPEP on either nicotine or
      food self-administration when administered into the VTA may be attributable
      either to actions of MPEP at presynaptic mGlu5 receptors or at targets other than
      mGlu5 receptors. Importantly, anatomical control injections 2mm above the NAcc
      shell or the VTA using the most effective MPEP dose in the two regions did not
      result in attenuation of nicotine self-administration. In conclusion, MPEP
      microinfusions in the VTA or NAcc shell attenuates the reinforcing effects of
      nicotine possibly via blockade of mGlu5 receptors located in these regions.

PMID- 21896279
TI  - The role of lateral occipital face and object areas in the face inversion effect.
AB  - Stimulus inversion impairs face discrimination to a greater extent than
      discrimination of other non-face object categories. This finding has led to
      suggestions that upright faces are represented by mechanisms specialized for
      upright faces whereas inverted face representation depends on more general object
      recognition mechanisms. In the present study we tested the causal role of face
      selective and object-selective cortical areas for upright and inverted face
      discrimination by transiently disrupting neural processing using transcranial
      magnetic stimulation (TMS). Participants matched upright and inverted faces while
      TMS was delivered over each participant's functionally localized right occipital
      face area (rOFA) or right lateral occipital area (rLO). TMS delivered over rOFA
      disrupted the discrimination of upright and inverted faces while TMS delivered
      over rLO impaired inverted face discrimination only. These results provide causal
      evidence that upright faces are represented by face-specific mechanisms whereas
      inverted faces are represented by both face-specific and object-specific
      mechanisms. The similar sensitivity of the OFA to upright and inverted faces is
      consistent with the hypothesis that the OFA processes facial features at an early
      stage of face processing.

PMID- 21896280
TI  - The protein synthesis inhibitor anisomycin reduces sex behavior during a critical
      period after testosterone treatment in male Syrian hamsters.
AB  - Testosterone (T) is critical for maintaining male sexual behavior (MSB) in
      rodents, in part by altering protein synthesis in a well-defined neural circuit.
      The specific timing of protein synthesis essential for expression of MSB has
      never been investigated. We administered the protein synthesis inhibitor
      anisomycin (Ani) to castrated male Syrian hamsters treated sc with 100 MUg T in
      an aqueous vehicle once weekly; this T regimen maintains MSB while elevating
      circulating T concentrations for only a few hours after each injection. Hamsters
      were injected s.c. with the vehicle or 12.5 mg Ani at one of several times
      relative to T administration; MSB was assessed once per week, 6 days after the
      previous T injection, for 5 weeks. Anisomycin administered 6-12 h after T
      injection significantly reduced the expression of sexual behavior, whereas Ani
      treatment between 3 h before and 3 h after T injection did not impair MSB. This
      experiment is the first to assess the specific timing of protein synthesis
      relative to a T pulse that is required for the expression of MSB. The demarcation
      of a critical interval for T-induced protein synthesis necessary for maintenance
      of MSB should facilitate specification of the genomic, proteomic, and biochemical
      cascades that subserve actions of T on male copulation.

PMID- 21896281
TI  - Insights into the local pathogenesis induced by fish toxins: role of natterins
      and nattectin in the disruption of cell-cell and cell-extracellular matrix
      interactions and modulation of cell migration.
AB  - Combined proteomic and transcriptomic approaches to study the composition of the
      venom of Thalassophryne nattereri venomous fish revealed the primary structures
      of the major toxins as a family of proteases natterins, never described on venoms
      and a C-type lectin nattectin. To gain new insights into the mechanisms of venom
      pathogenesis and to further elucidate the role of its major toxins, the natterins
      and nattectin, we undertook in vitro investigations using these isolated toxins.
      Here we demonstrated the specific ability of the nattectin to bind types I and V
      collagen and natterins to bind and cleave type I collagen as well as type IV
      collagen, disrupting cell attachment and HeLa cells survival. Natterins have
      cytotoxic effect on both adherent cells or at in suspension, showing direct
      induction of necrosis that is followed by cell detachment. Nattectin improves
      integrin-mediated HeLa cell adhesion and resistance to apoptosis by its binding
      to RGD-dependent integrins, especially the beta1 subunit. Based on our studies we
      now report that extracellular matrix (ECM) components as well as the integrin
      beta1 subunit are targets for the natterins and nattectin. The ECM degradation or
      remodeling activities exerted by these toxins affect cell-cell and cell-ECM
      adhesion and survival and impair inflammatory cell migration into inflamed
      tissues.

PMID- 21896282
TI  - In vitro antioxidant activities of sulfated polysaccharide fractions extracted
      from Corallina officinalis.
AB  - Sulfated polysaccharides (F1, F2) from seaweed Corallina officinalis were
      isolated through anion-exchange column chromatography. Their chemical
      characteristics were determined by GC, HPLC, FT-IR and UV spectra. F1 and F2
      contained only two monosaccharides, namely galactose and xylose. The antioxidant
      activities of F1, F2 and the de-sulfated polysaccharides (DF-1, DF-2) in vitro
      were investigated, including hydroxyl radicals scavenging effect, superoxide
      radical scavenging capacity, DPPH radical activity and reducing power. As
      expected, antioxidant assay showed that the two sulfated polysaccharide fractions
      (F1, F2) possessed considerable antioxidant properties and had more excellent
      abilities than de-sulfated polysaccharides (DF-1, DF-2).

PMID- 21896283
TI  - Structural and functional diversity of the lectin repertoire in teleost fish:
      relevance to innate and adaptive immunity.
AB  - Protein-carbohydrate interactions mediated by lectins have been recognized as key
      components of innate immunity in vertebrates and invertebrates, not only for
      recognition of potential pathogens, but also for participating in downstream
      effector functions, such as their agglutination, immobilization, and complement
      mediated opsonization and killing. More recently, lectins have been identified as
      critical regulators of mammalian adaptive immune responses. Fish are endowed with
      virtually all components of the mammalian adaptive immunity, and are equipped
      with a complex lectin repertoire. In this review, we discuss evidence suggesting
      that: (a) lectin repertoires in teleost fish are highly diversified, and include
      not only representatives of the lectin families described in mammals, but also
      members of lectin families described for the first time in fish species; (b) the
      tissue-specific expression and localization of the diverse lectin repertoires and
      their molecular partners is consistent with their distinct biological roles in
      innate and adaptive immunity; (c) although some lectins may bind endogenous
      ligands, others bind sugars on the surface of potential pathogens; (d) in
      addition to pathogen recognition and opsonization, some lectins display
      additional effector roles, such as complement activation and regulation of immune
      functions; (e) some lectins that recognize exogenous ligands mediate processes
      unrelated to immunity: they may act as anti-freeze proteins or prevent
      polyspermia during fertilization.

PMID- 21896285
TI  - Evaluation of MUECoG electrode arrays in the minipig: experimental procedure and
      neurosurgical approach.
AB  - Emerging research on brain-machine interfaces (BMIs) requires the development of
      animal models for testing implantable BMI electrodes. New models are necessary in
      order to characterize and test newly constructed electrodes in an acute
      environment, and their properties and performance need to be evaluated in long
      term, chronic implantations. Owing to their availability, small size and
      neuroanatomical similarity to the human brain, minipigs are frequently used for
      neurological studies. Despite this fact, there are still no standardized
      experimental and neurosurgical procedures available for recording of cortical
      potentials using implantable BMI electrodes in minipigs, and, until now, it was
      unclear whether these animals could also be used for long-term subdural electrode
      implantations. We have therefore evaluated the potential use of minipigs for
      acute and chronic implantation of micro-electrocorticogram (MUECoG) electrodes we
      newly developed for BMI applications and we present a standardized neurosurgical
      approach to the minipig's cerebral cortex. A neurophysiological setup is
      described which is suitable to perform recordings of somatosensory evoked
      potentials (SEPs) with high spatial resolution - down to approx. 1-mm inter
      electrode distance. Perioperative management, anesthesia and anatomical landmarks
      for electrode placement are discussed and common surgical pitfalls are described.
      While, due to their specific cranial anatomy, minipigs appear not optimally
      suited for chronic subdural implantations, the findings of the present study
      indicate that MUECoG recording from the minipig cortex is a valuable new approach
      for acute in vivo characterization of subdural BMI electrode function.

PMID- 21896284
TI  - Tonic and phasic release of glutamate and acetylcholine neurotransmission in sub
      regions of the rat prefrontal cortex using enzyme-based microelectrode arrays.
AB  - The medial prefrontal cortex (mPFC) is an area of the brain critical for higher
      cognitive processes and implicated in disorders of the CNS such as drug
      addiction, depression and schizophrenia. Glutamate and acetylcholine are
      neurotransmitters that are essential for cortical functioning, yet little is
      known about the dynamic function of these neurotransmitters in subregions of the
      mPFC. In these studies we used a novel microelectrode array technology to measure
      resting levels (tonic release) of glutamate and acetylcholine as well as KCl
      evoked release (stimulated phasic release) in the mPFC of the anesthetized rat to
      further our understanding of both tonic and phasic neurotransmission in the
      cingulate cortex, prelimbic cortex, and infralimbic cortex of the mPFC. Studies
      revealed homogeneity of tonic and phasic signaling among brain subregions for
      each neurotransmitter. However, resting levels of glutamate were significantly
      higher as compared to acetylcholine levels in all subregions. Additionally, KCl
      evoked acetylcholine release in the cingulate cortex (7.1 MUM) was significantly
      greater than KCl-evoked glutamate release in any of the three subregions (Cg1,
      2.9 MUM; PrL, 2.0 MUM; IL, 1.8 MUM). Interestingly, the time for signal decay
      following KCl-evoked acetylcholine release was significantly longer by an average
      of 240% as compared to KCL-evoked glutamate release for all three brain
      subregions. Finally, we observed a negative relationship between acetylcholine
      resting levels and KCl-evoked release in the Cg1. These data suggest a homogenous
      distribution of both glutamatergic and acetylcholinergic innervation in the mPFC,
      with alterations in tonic and phasic release regulation accounting for
      differences between these neurotransmitters.

PMID- 21896286
TI  - Protective effect of pristane on experimental autoimmune uveitis.
AB  - This study evaluates the effects of pristane and phytol, two mineral oils with
      pro-oxidative effects, on the course of experimental autoimmune uveitis. C57BL6
      mice were immunized with IRBP1-20 peptide emulsified in CFA and treated five days
      prior to immunization with phytol or with pristane or with PBS as control.
      Administration of pristane reduces the incidence and severity of IRBP-induced
      uveitis as demonstrated by the decrease in vasculitis and inflammatory foci in
      fundus and by a reduction in histological damages and leukocyte infiltration
      compared to untreated or phytol-treated mice. The protective effect observed is
      associated with a decreased activation of peripheral CD4+ and CD8+ T lymphocytes
      and a decrease in the intensity of the Th1 and Th17 autoimmune response to IRBP
      in pristane-treated mice compared to control mice, as evidenced by the decreased
      production of IFNgamma and IL17 by IRBP-specific lymphocytes from lymph nodes
      draining the site of immunization and by the increased production of anti-IRBP
      IgG1 over IgG2a. In addition, HUVEC and ARPE-19 cells incubated with the sera of
      mice treated with pristane presented a reduced production of H(2)O(2). The
      benefit of lowering the systemic oxidative stress by pristane in the course of
      EAU was confirmed by injecting the antioxidant NAC in IRBP-immunized mice. As
      pristane, NAC decreased clinical and histological inflammation of the retina and
      preserved the integrity of the hemato-retinal barrier. Finally, the protective
      effect of pristane on the development of EAU suggests that some mineral oils may
      represent a new therapeutic strategy in human uveitis.

PMID- 21896287
TI  - Zoonotic Brazilian Vaccinia virus: from field to therapy.
AB  - Vaccinia virus (VACV), the prototype species of the Orthopoxvirus (OPV) genus,
      causes an occupational zoonotic disease in Brazil that is primarily associated
      with the handling of infected dairy cattle. Cattle and human outbreaks have been
      described in southeastern Brazil since 1999 and have now occurred in almost half
      of the territory. Phylogenetic studies have shown high levels of polymorphisms
      among isolated VACVs, which indicate the existence of at least two genetically
      divergent clades; this has also been proven in virulence assays in a mouse model
      system. In humans, VACV infection is characterized by skin lesions, primarily on
      the hands, accompanied by systemic symptoms such as fever, myalgia, headache and
      lymphadenopathy. In this review, we will discuss the virological,
      epidemiological, ecological and clinical aspects of VACV infection, its diagnosis
      and compounds that potentially could be used for the treatment of severe cases.

PMID- 21896288
TI  - HIV-1 reverse transcriptase connection subdomain mutations involved in resistance
      to approved non-nucleoside inhibitors.
AB  - The human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) is a
      major target of antiretroviral intervention. Non-nucleoside RT inhibitors
      (NNRTIs) bind to a hydrophobic pocket located away from the DNA polymerase
      catalytic site of the RT. Approved NNRTIs are nevirapine, delavirdine, efavirenz,
      etravirine and rilpivirine. This review describes how these inhibitors affect RT
      function, the structural basis of NNRTI binding, and the role of specific amino
      acid substitutions at the NNRTI binding pocket in the acquisition of high-level
      drug resistance. However, two or more amino acid substitutions are required to
      achieve >20-fold decreased susceptibility to recently developed NNRTIs such as
      etravirine or rilpivirine, in phenotypic assays. While genotypic analysis of HIV
      1 isolates in infected patients is usually restricted to residues 1-250 of the
      RT, recent reports indicate that several residues in the connection subdomain of
      the RT (comprising residues 319-426) could also modulate NNRTI resistance.
      Examples are Y318F or W, N348I, A376S and T369I or V. Tyr-318 participates in
      NNRTI binding, but other amino acid substitutions in the connection subdomain may
      affect resistance through an indirect mechanism. Studies on the effects of N348I
      and A376S on NNRTI resistance indicate that these changes could affect inhibitor
      binding by altering the interaction between RT subunits or between the RT and the
      template-primer. Moreover, those mutations could also modulate RNase H activity
      not only during DNA strand elongation, but also at the initiation of plus strand
      DNA synthesis as demonstrated for the N348I mutation.

PMID- 21896289
TI  - Voluntary wheel running enhances contextual but not trace fear conditioning.
AB  - Exercise improves performance on a number of hippocampus involved cognitive tasks
      including contextual fear conditioning, but whether exercise enhances contextual
      fear when the retention interval is longer than 1 day is not known. Also unknown
      is whether exercise improves trace conditioning, a task that requires the
      hippocampus to bridge the time interval between stimuli. Hence, 4-month-old male
      C57BL/6J mice were housed with or without running wheels. To assess whether
      hippocampal neurogenesis was associated with behavioral outcomes, during the
      initial 10 days, mice received Bromodeoxyuridine to label dividing cells. After
      30 days, one group of mice was trained in a contextual fear conditioning task.
      Freezing to context was assessed 1, 7, or 21 days post-training. A separate group
      was trained on a trace procedure, in which a tone and footshock were separated by
      a 15, 30, or 45s interval. Freezing to the tone was measured 24h later in a novel
      environment, and freezing to the training context was measured 48h later. Running
      enhanced freezing to context when the retention interval was 1, but not 7 or 21
      days. Running had no effect on trace conditioning even though runners displayed
      enhanced freezing to the training context 48h later. Wheel running increased
      survival of new neurons in the hippocampus. Collectively, findings indicate that
      wheel running enhances cognitive performance on some tasks but not others and
      that enhanced neurogenesis is not always associated with improved performance on
      hippocampus tasks, one example of which is trace conditioning.

PMID- 21896290
TI  - Distinct behavioral consequences of stress models of depression in the elevated T
      maze.
AB  - Animals exposed to inescapable stress develop behavioral consequences that are
      similar to symptoms of depression. Therefore, most of the animal models of
      depression are based on animal exposure to such stressors. The stress-induced
      behavioral consequences induced by pre-exposure to shock in the learned
      helplessness model of depression have been proposed to be a consequence of
      excessive activation of fear/anxiety related structures which would lead to
      inhibitory avoidance and impaired escape performance. However, this hypothesis
      has not yet been investigated in a test that is able to generate these different
      defense strategies in a same rat, such as the elevated T-maze (ETM). Therefore,
      the objective of the present study was to test the effects of footshock pre
      exposure (inescapable-IS or escapable-ES) on both inhibitory avoidance and escape
      responses of rats submitted to the ETM 24 h later. Moreover, since it is not
      known whether these effects would be a common feature to other inescapable
      stressors used as animal models of depression, we have also investigated the
      behavior of rats previously exposed to forced swimming or restraint. All stressed
      groups displayed anxiogenic-like behavior when compared to control groups (non
      stressed), evidenced by facilitated acquisition of inhibitory avoidance in the
      ETM. However, only rats exposed to IS showed impaired escape performance. These
      results support the hypothesis that the facilitated inhibitory avoidance is a
      common behavioral consequence of distinct stressful stimuli. However, the
      impaired escape response is likely to be particularly involved in the mediation
      of the helpless behavior observed in rats pre-exposed to IS. The neurobiological
      mechanisms involved in these responses are discussed in the manuscript.

PMID- 21896291
TI  - Neurotensin decreases high affinity [3H]-ouabain binding to cerebral cortex
      membranes.
AB  - Previous work from this laboratory showed the ability of neurotensin to inhibit
      synaptosomal membrane Na(+), K(+)-ATPase activity, the effect being blocked by SR
      48692, a non-peptidic antagonist for high affinity neurotensin receptor (NTS1)
      [Lopez Ordieres and Rodriguez de Lores Arnaiz 2000; 2001]. To further study
      neurotensin interaction with Na(+), K(+)-ATPase, peptide effect on high affinity
      [(3)H]-ouabain binding was studied in cerebral cortex membranes. It was observed
      that neurotensin modified binding in a dose-dependent manner, leading to 80%
      decrease with 1 * 10(-4)M concentration. On the other hand, the single addition
      of 1 * 10(-6)M, 1 * 10(-5)M and 1 * 10(-4)M SR 48692 (Sanofi-Aventis, U.S., Inc.)
      decreased [(3)H]-ouabain binding (in %) to 87 +/- 16; 74 +/- 16 and 34 +/- 17,
      respectively. Simultaneous addition of neurotensin and SR 48692 led to additive
      or synergic effects. Partial NTS2 agonist levocabastine inhibited [(3)H]-ouabain
      binding likewise. Saturation assays followed by Scatchard analyses showed that
      neurotensin increased K(d) value whereas failed to modify B(max) value,
      indicating a competitive type interaction of the peptide at Na(+), K(+)-ATPase
      ouabain site. At variance, SR 48692 decreased B(max) value whereas it did not
      modify K(d) value. [(3)H]-ouabain binding was also studied in cerebral cortex
      membranes obtained from rats injected i. p. 30 min earlier with 100 MUg and 250
      MUg/kg SR 48692. It was observed that the 250 MUg/kg SR 48692 dose led to 19%
      decrease in basal [(3)H]-ouabain binding. After SR 48692 treatments, addition of
      1 * 10(-6)M led to additive or synergic effect. Results suggested that [(3)H]
      ouabain binding inhibition by neurotensin hardly involves NTS1 receptor.

PMID- 21896292
TI  - Purification of modified mycobacterial A60 antigen by affinity chromatography and
      its use for rapid diagnostic tuberculosis infection.
AB  - Tuberculosis has been declared a global emergency. The mainstay for its control
      is the rapid and accurate identification of infected individual. Antibodies to
      A60, one of the macromolecular antigen complexes of mycobacteria were commonly
      used in the rapid detection of Mycobacterium tuberculosis. The aim of this study
      was to prepare specific antibodies against A60 for detection of tuberculosis
      infection. Specific polyclonal antibodies against A60, (A60-Ab) were prepared in
      rabbits using 2 boosted injections of the antigen (A60). The antibodies were
      purified and treated with normal oral flora to remove any non-specific and cross
      reactive antibodies. These antibodies were conjugated to CNBr-activated Sepharose
      4B and used to isolate subunits of A60 with more specificity for M. tuberculosis.
      A new affinity column was designed to prepare modified (purified) A60 antigen.
      Purified A60 antigen (PA60-Ag) was used to develop antibody production by
      Immunoaffinity chromatography. 113 patients with a confirmed diagnosis of
      pulmonary TB at Pasteur Institute were selected for the study. The specificity of
      the results was analyzed with TB-rapid test by using PA60-antibodies. TB-rapid
      test revealed that normal oral flora-absorbed antibodies could lead to more
      specific results than that of the non-absorbed antibodies. The developed,
      modified A60 antibodies, (PA60-Ab)-rapid test showed higher sensitivity,
      specificity, Positive Predictive Value (PPV), Negative Predictive Value (NPV) and
      overall efficiency (93.0%, 86.0%, 90.0%, 91.0%, and 90.0% respectively) for the
      detection of the Mycobacterium antigen. Moreover, PA60-Ag showed only two protein
      bands of molecular weight 45 and 66kDa in SDS-PAGE while untreated A60 showed
      multiple bands. Thus, our study helped in the purification of a novel and well
      characterized A60 antigen and good diagnostic potential for detecting
      tuberculosis infection.

PMID- 21896293
TI  - Changes in the topology of gene expression networks by human immunodeficiency
      virus type 1 (HIV-1) integration in macrophages.
AB  - One key step of human immunodeficiency virus type 1 (HIV-1) infection is the
      integration of its viral cDNA. This process is mediated through complex networks
      of host-virus interactions that alter several normal cell functions of the host.
      To study the complexity of disturbances in cell gene expression networks by HIV-1
      integration, we constructed a network of human macrophage genes located close to
      chromatin regions rich in proviruses. To perform the network analysis, we
      selected 28 genes previously identified as the target of cDNA integration and
      their transcriptional profiles were obtained from GEO Profiles (NCBI). A total of
      2770 interactions among the 28 genes located around the HIV-1 proviruses in human
      macrophages formed a highly dense main network connected to five sub-networks.
      The overall network was significantly enriched by genes associated with signal
      transduction, cellular communication and regulatory processes. To simulate the
      effects of HIV-1 integration in infected macrophages, five genes with the most
      number of interaction in the normal network were turned off by putting in zero
      the correspondent expression values. The HIV-1 infected network showed changes in
      its topology and alteration in the macrophage functions reflected in a re
      programming of biosynthetic and general metabolic process. Understanding the
      complex virus-host interactions that occur during HIV-1 integration, may provided
      valuable genomic information to develop new antiviral treatments focusing on the
      management of some specific gene expression networks associated with viral
      integration. This is the first gene network which describes the human macrophages
      genes interactions related with HIV-1 integration.

PMID- 21896294
TI  - Eating green. Consumers' willingness to adopt ecological food consumption
      behaviors.
AB  - Food consumption is associated with various environmental impacts, and consumers'
      food choices therefore represent important environmental decisions. In a large
      scale survey, we examined consumers' beliefs about ecological food consumption
      and their willingness to adopt such behaviors. Additionally, we investigated in
      more detail how different motives and food-related attitudes influenced
      consumers' willingness to reduce meat consumption and to buy seasonal fruits and
      vegetables. We found consumers believed avoiding excessive packaging had the
      strongest impact on the environment, whereas they rated purchasing organic food
      and reducing meat consumption as least environmentally beneficial. Similarly,
      respondents appeared to be most unwilling to reduce meat consumption and purchase
      organic food. Taste and environmental motives influenced consumers' willingness
      to eat seasonal fruits and vegetables, whereas preparedness to reduce meat
      consumption was influenced by health and ethical motives. Women and respondents
      who preferred natural foods were more willing to adopt ecological food
      consumption patterns.

PMID- 21896295
TI  - Food avoidance in children. The influence of maternal feeding practices and
      behaviours.
AB  - The aim of this study was to examine the contribution of a broad range of
      maternal feeding practices in predicting parental reports of food avoidance
      eating behaviours in young children, after controlling for child temperament, and
      maternal dietary restraint which have previously been associated with feeding
      problems. One hundred and four mothers of children aged between 3 and 6 years
      completed self report measures of their child's eating behaviour and temperament,
      maternal dietary restraint and child feeding practices. Maternal reports of food
      avoidance eating behaviours were associated with an emotional child temperament,
      high levels of maternal feeding control, using food for behaviour regulation and
      low encouragement of a balanced and varied food intake. Maternal feeding
      practices, predominantly pressure to eat, significantly predicted food avoidance
      eating behaviours after controlling for child emotionality and maternal dietary
      restraint. The significant contribution of maternal feeding practices, which are
      potentially modifiable behaviours, suggests that the feeding interactions of
      parents and their children should be targeted for intervention and the prevention
      of feeding difficulties during early childhood. Future research should continue
      to explore how a broader range of feeding practices, particular those that may be
      more adaptive, might influence child eating behaviour.

PMID- 21896296
TI  - Implicit wanting and explicit liking are markers for trait binge eating. A
      susceptible phenotype for overeating.
AB  - The present study used a measure of trait binge eating (Binge Eating Scale; BES)
      to examine its association with behavioural markers of appetite and food reward.
      Non-obese female participants consumed a preload before freely selecting and
      consuming from a test meal. Subjective hunger and hedonic measures of explicit
      liking and implicit wanting for food were obtained. Food selection and intake of
      the test meal were measured. Findings were compared according to individual
      differences in trait binge eating. BES scores correlated with BMI, food intake
      and selection of high fat sweet foods in the test meal. Comparison of BES scores
      revealed that higher scores were associated with weaker suppression of hunger
      after the preload, greater explicit liking for food generally, and increased
      implicit wanting for high fat sweet food. Trait binge eating is functional at low
      levels and implicit wanting measured simultaneously with explicit liking may be
      useful markers for reward-driven overconsumption in this susceptible phenotype.

PMID- 21896297
TI  - Parent- and child-reported parenting. Associations with child weight-related
      outcomes.
AB  - The present study aimed to investigate associations of both parent-reported and
      child-perceived parenting styles and parent-reported parenting practices with
      child weight and weight-related behaviours. Participants were 175 children (56%
      female) aged between 7 and 11, and their primary caregivers (91% female),
      recruited through South Australian primary schools. Children completed measures
      of parenting style, attitude toward fruit, vegetables, and non-core food, and
      attraction to physical activity. Parents completed measures of parenting style
      and domain-specific parenting practices (feeding and activity-related practices)
      and reported on child dietary intake, physical activity, and sedentary behaviour.
      Objective height and weight measurements were taken from children, from which
      body mass index (BMI) was calculated. Child-reported parenting style and parent
      reported parenting practices were uniquely associated with child weight-related
      outcomes, but styles and practices did not interact in their association with
      child outcomes. Child-reported parenting style was associated with child food and
      activity attitudes, whereas parent-reported parenting style was not associated
      with child outcomes. The findings of the present study generally support the
      recommendation of a parenting style high in demandingness and responsiveness for
      supporting healthy child weight-related behaviours, along with appropriate domain
      specific practices. The child's perspective should be incorporated into research
      involving child outcomes wherever possible.

PMID- 21896298
TI  - Parent use of food to soothe infant/toddler distress and child weight status. An
      exploratory study.
AB  - The aim of the present study was to explore the parent feeding practice of using
      food to soothe infant/toddler distress and its relationship to child weight
      status. Seventy eight families with infants and toddlers (43 males) ranging in
      age from 3 to 34 months (M=14 mos, SD=9 mos) completed a survey which included
      questions on their use of food to soothe, questionnaires on parent feeding
      practices, parenting self-efficacy, child temperament and child's weight and
      length at the time of their last well-baby visit. Results revealed the use of
      food to soothe to be a valid construct. In addition, mothers who used food to
      soothe rated themselves lower in parenting self-efficacy and their children
      higher in temperamental negativity. Analyses examining weight status as the
      outcome variable revealed that mothers who reported the use of food to soothe had
      heavier children, however, this relationship was stronger for children rated as
      high in temperamental negativity.

PMID- 21896299
TI  - Mucosal immunity and poliovirus vaccines: impact on wild poliovirus infection and
      transmission.
AB  - Since the resolution of the World Assembly in 1988 to eradicate polio globally,
      substantial progress toward this target has been achieved, but the final goal
      remains elusive. India and other tropical developing countries present a unique
      challenge because of the much lower oral poliovirus vaccine (OPV) immunogenicity
      compared to industrialized countries, both in terms of humoral and mucosal
      immunity. To overcome this challenge, further research is needed to elucidate the
      causes for the suboptimal OPV immunogenicity, better defining the optimal vaccine
      schedules and delivery strategies, developing and evaluating adjuvants to boost
      OPV immunogenicity, and improving the methods for directly measuring mucosal
      immunity.

PMID- 21896300
TI  - Elevated plasma superoxide dismutase in first-episode and drug naive patients
      with schizophrenia: inverse association with positive symptoms.
AB  - Excessive free radical production or oxidative stress may be involved in the
      pathophysiology of schizophrenia as evidenced by increased superoxide dismutase
      (SOD) activities, a critical enzyme in the detoxification of superoxide radicals.
      This study compared plasma SOD activities in 78 never-medicated first-episode and
      100 medicated chronic schizophrenia patients to 100 healthy control subjects and
      correlated these SOD activities with the Positive and Negative Syndrome Scale
      (PANSS) among the schizophrenic patients. We found that both first-episode and
      chronic patients had significantly increased plasma SOD activities compared to
      controls, and that chronic schizophrenic patients on antipsychotic medication had
      significantly higher SOD activities than first episode schizophrenic patients.
      Plasma SOD activities were also negatively correlated with positive symptoms of
      schizophrenia, but only in first-episode patients. Thus, oxidative stress appears
      to be greater in first episode schizophrenic patients with fewer positive
      symptoms and may become greater as schizophrenia becomes more chronic, although
      we cannot exclude the possibility that chronic antipsychotic treatment may
      increase SOD activities and presumed oxidative stress in schizophrenia.

PMID- 21896301
TI  - What are the optimal pharmacokinetic properties of antipsychotic medications?
AB  - Sensitization of the dopaminergic system has been proposed as a pathogenic
      mechanism of psychosis. It has been reported in sensitized animals that the
      proportion of high-affinity dopamine 2 (D2) receptors is increased, without
      changes in the total amount of D2 receptors. This increase induces an exaggerated
      postsynaptic transmission of the dopamine signal, which is attenuated by
      antipsychotic D2 antagonists. In this report, I simulated D2 receptor binding of
      dopamine and antipsychotics under pathologic state, and investigated
      pharmacological conditions that would return the increased dopamine binding back
      to normal levels in both resting and burst dopamine concentrations. I found that
      D2 antagonists with small Koff values at a concentration 2.5 times the Ki closely
      mimicked normal dopamine binding. Under these conditions, the apparent receptor
      occupancy of the drug was calculated as 70%.

PMID- 21896302
TI  - Protective effects of apricot kernel oil on myocardium against ischemia
      reperfusion injury in rats.
AB  - The present study was undertaken to evaluate the potential cardioprotective
      effects of apricot kernel oil (AO) on the myocardial ischemia-reperfusion (IR) of
      rat model in vivo. The rats were divided into five groups: sham-operated, IR, low
      dose AO-treated IR (LD-AO+IR), medium dose AO-treated IR (MD-AO+IR) and high dose
      AO-treated IR (HD-AO+IR). All rats were provided with food and water ad libitum.
      The LD-AO+IR, MD-AO+IR and HD-AO+IR groups were given a daily dose of 2, 6 and 10
      ml kg(-1)BW(-1) of AO, respectively, for 14 days prior to the IR operation.
      Tetrazolium chloride staining revealed that infarct size and the ratio of infarct
      weight to the total heart weight were decreased significantly in the three AO
      treated groups compared to the IR group. The serum creatine kinase and aspartate
      aminotransferase activities also demonstrated similar beneficial effects.
      Myocardial catalase, superoxide dismutase, glutathione peroxidase, and
      constitutive nitric oxide synthase activities, as well as NO concentrations, were
      all increased, whereas malondialdehyde content and inducible nitric oxide
      synthase were decreased in AO-treated rats. These findings suggest that apricot
      kernel oil has potent cardioprotective effects, and could be developed as a
      nutriment for the treatment and prevention of myocardial infarcts.

PMID- 21896303
TI  - Effects of periodic fluoride treatment on fluoride ion release from fresh
      orthodontic adhesives.
AB  - OBJECTIVE: Periodic fluoride treatment may contribute to the ability of fresh
      orthodontic adhesives to provide long-term F(-) release. The effects of periodic
      fluoride treatment on the amount of F(-) release from fresh orthodontic adhesives
      was investigated. METHODS: F(-) release was measured from a nonfluoride-releasing
      composite, a fluoride-releasing composite, a polyacid-modified composite
      (compomer), and two resin-modified glass-ionomer cements (RMGICs) at 1, 2, and 5
      days after one of the following treatments: 225 ppm F(-) solution, 900 ppm F(-)
      solution, acidulated phosphate fluoride gel (APF), fluoridated dentifrice, and
      deionised water (control). F(-) release was measured in a 5-day cycle, which was
      repeated 9 consecutive times. The amount of F(-) release for each group was
      analysed using the repeated measures analysis of variance. Statistical
      significance was set at a level of alpha=0.05. RESULTS: Periodic fluoride
      treatment temporarily increased F(-) release in fresh fluoride-releasing
      orthodontic adhesives, but not in fresh nonfluoride-releasing composite. The
      order of effective fluoride-release was RMGICs>compomer>fluoride-releasing
      composite>nonfluoride-releasing composite. The application of APF or 900 ppm F(-)
      solution was the most effective way to maintain F(-) release from fresh
      orthodontic adhesives. However, the amount of F(-) release gradually decreased
      with increasing specimen age. CONCLUSION: Given the difficulty of routine use of
      APF at home, the results of this study show that a combination of RMGICs and high
      dose fluoride mouth rinse is the most effective protocol to maintain F(-) release
      from fresh orthodontic adhesives. CLINICAL SIGNIFICANCE: Most studies have
      investigated fluoride-uptake abilities using aged materials in which fluoride had
      been lost for at least 1 month. This study has found that periodic fluoride
      treatment altered the conventional F(-) release pattern of fresh fluoride
      releasing materials and type of fluoride-containing medium plays a more critical
      role in fluoride recharging of the materials than fluoride concentration. This
      study will help clinicians to find the most effective fluoride treatment protocol
      of fresh materials.

PMID- 21896304
TI  - Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in
      colorectal carcinomas.
AB  - Cathepsin S is a lysosomal cysteine protease implicated in tumourigenesis with
      key roles in invasion and angiogenesis. We have previously shown that the
      specific inhibition of Cathepsin S using a monoclonal antibody (Fsn0503) blocks
      colorectal carcinoma tumour growth and angiogenesis in vivo. We investigated
      whether Cathepsin S expression levels were affected by chemotherapy in human
      cancer cell lines by RT-PCR. Using colorectal xenograft models, we examined the
      therapeutic benefit of Cathepsin S inhibition using Fsn0503 in combination with a
      metronomic dosing regimen of CPT-11. We analysed the effects of the combination
      therapy on tumour progression and on tumour vascularisation by
      immunohistochemical staining of tumours. Cathepsin S expression levels are
      upregulated in HCT116, LoVo, Colo205 cell lines and HUVECs after exposure to CPT
      11 in vitro. The administration of Fsn0503 in combination with CPT-11
      significantly attenuated tumour growth in comparison to CPT-11 alone in
      colorectal HCT116 xenograft models. Furthermore, analysis of tumour
      vascularisation revealed that this was also significantly disrupted by the
      combination treatment. These results show that the combination of Cathepsin S
      inhibition with CPT-11 enhances the therapeutic effect of the chemotherapy. This
      rationale may have clinical application in the treatment of colorectal cancer
      upon further evaluation.

PMID- 21896305
TI  - Turning pyridoxal-5'-phosphate-dependent enzymes into thermostable binding
      proteins: D-Serine dehydratase from baker's yeast as a case study.
AB  - D-serine dehydratase from Saccharomyces cerevisae is a recently discovered
      dimeric enzyme catalyzing the beta-elimination of D-serine to pyruvate and
      ammonia. The reaction is highly enantioselective and depends on cofactor
      pyridoxal-5'-phosphate (PLP) and Zn(2+). In our work, the aldimine linkage
      tethering PLP to recombinant, tagged D-serine dehydratase (Dsd) has been reduced
      by treatment with NaBH(4) so as to yield an inactive form of the holoenzyme
      (DsdR), which was further treated with a protease in order to remove the amino
      terminal purification tag. Fourier Transform infrared (FT-IR) spectroscopic
      analysis revealed that both the reduced form (DsdR) and the reduced/detagged form
      (DsdRD) maintain the overall secondary structure of Dsd, but featured a
      significant increased thermal stability. The observed T(m) values for DsdR and
      for DsdRD shifted to 71.5  degrees C and 73.3  degrees C, respectively, resulting
      in nearly 11  degrees C and 13  degrees C higher than the one measured for Dsd.
      Furthermore, the analysis of the FT-IR spectra acquired in the presence of D
      serine and L-serine indicates that, though catalytically inert, DsdRD retains the
      ability to enantioselectively bind its natural substrate. Sequence analysis of D
      serine dehydratase and other PLP-dependent enzymes also highlighted critical
      residues involved in PLP binding. In virtue of its intrinsic properties, DsdRD
      represents an ideal candidate for the design of novel platforms based on stable,
      non-consuming binding proteins aimed at measuring d-serine levels in biological
      fluids.

PMID- 21896306
TI  - Imaging biomarkers in Parkinson's disease.
AB  - Parkinson's disease (PD) is characterized by a progressive loss of nigrostriatal
      dopaminergic neurons associated with intracellular Lewy inclusion bodies. The
      result is poverty of movement, increased muscle rigidity, and tremor at rest and
      on posture. Midbrain/nigral structural abnormalities can be demonstrated in vivo
      with both transcranial sonography (TCS) and diffusion tensor magnetic resonance
      imaging (DTI) while positron emission tomography (PET) and single photon emission
      computed tomography (SPECT) ligands exist to demonstrate dopamine terminal
      dysfunction. These radiotracers are markers of dopamine storage capacity,
      vesicular monoamine and dopamine transporter availability. While loss of putamen
      dopaminergic function leads to motor disability, Lewy bodies not only target
      dopamine neurons but have also been observed in serotoninergic, noradrenergic,
      and cholinergic neurons. As a consequence, non-dopaminergic neurotransmission is
      also impaired resulting in non-motor symptoms including sleep disturbance,
      fatigue, depression, dementia, and autonomic dysfunction. PET and SPECT ligands
      exist to interrogate the function of monoaminergic and cholinergic neurons.
      Cortical and limbic Lewy body disease is seen in more advanced PD and this can be
      detected with FDG PET as abnormal covariance between levels of resting brain
      metabolism in these regions. Additionally, widespread microglial activation can
      be detected in PD with PET. This review discusses the role of structural and
      functional imaging for understanding parkinsonian syndromes and aiding in their
      diagnosis and management.

PMID- 21896307
TI  - RNA interference-directed silencing of VPAC1 receptor inhibits VIP effects on
      both EGFR and HER2 transactivation and VEGF secretion in human breast cancer
      cells.
AB  - We used small-interference RNA (siRNA) to explore the mechanisms of some
      vasoactive intestinal peptide (VIP) actions on human breast cancer cells.
      Transfection of estrogen-dependent (T47D) and estrogen-independent (MDA-MB-468)
      breast cancer cells with VPAC(1)-receptor siRNA completely abolished VIP
      stimulatory effect on secretion of the main angiogenic factor, vascular
      endothelial growth factor (VEGF), and transactivation of epidermal growth factor
      receptor (EGFR or HER1) and HER2, two members of HER family of tyrosine-kinase
      receptors. The silencing procedure suggested the involvement of EGFR and HER2
      transactivation in VIP-stimulated VEGF secretion. It was further supported by
      blocking tyrosine kinase activity by the selective HER inhibitors AG-1478 (EGFR)
      and AG-825 (HER2). Results give value to the specific signaling of VIP through
      VPAC(1) receptor in human breast cancer cells and support the potential use of
      VPAC(1)-receptor antagonists in combined targeted therapies for breast cancer.
      Molecular therapies involving RNA interference of VPAC(1)-receptor expression
      could also be considered.

PMID- 21896308
TI  - In vivo 5-HT(6) receptor occupancy by antipsychotic drugs in the rat brain.
AB  - The 5-HT(6) receptor subtype is predominantly expressed in the central nervous
      system, and preclinical evidence suggests that it plays a critical role in the
      regulation of molecular pathways underlying cognitive function. Patients with
      schizophrenia show cognitive impairment as a fundamental symptom, and it is
      proposed that the procognitive properties of some antipsychotics such as
      olanzapine and clozapine would be, in part, due to the central blockade of 5
      HT(6) receptors. In this study, we characterized the brain 5-HT(6) receptor
      occupancy of olanzapine, clozapine and chlorpromazine in relation to their
      pharmacokinetic profiles using in vivo [(3)H]GSK215083 binding assay in rat
      brain. Oral administration of olanzapine (3mg/kg), clozapine (30mg/kg) and
      chlorpromazine (30mg/kg) produced significant 5-HT(6) receptor occupancy in the
      brain, inhibiting radioligand binding by 88, 97 and 81%, respectively. The blood
      concentrations required to achieve significant occupancy were clinically
      achievable (9.6, 26.9 and 98.6nM for olanzapine, clozapine and chlorpromazine,
      respectively). This data provides preclinical evidence to support the hypothesis
      that brain 5-HT(6) antagonism contributes to the procognitive properties of
      antipsychotic drugs such as olanzapine and clozapine.

PMID- 21896309
TI  - Protective role of the ubiquitin binding protein Tollip against the toxicity of
      polyglutamine-expansion proteins.
AB  - Huntington disease (HD) is caused by the expansion of polyglutamine (polyQ)
      repeats in the amino-terminal of hungtintin (htt). PolyQ-expanded htt forms
      intracellular ubiquitinated aggregates in neurons and causes neuronal cell death.
      Here, utilizing a HD cellular model, we report that Tollip, an ubiquitin binding
      protein that participates in intracellular transport via endosomes, co-localizes
      with and stimulates aggregation of polyQ-expanded amino-terminal htt.
      Furthermore, we demonstrate that Tollip protects cells against the toxicity of
      polyQ-expanded htt. We propose that association of Tollip with polyubiquitin
      accelerates aggregation of toxic htt species into inclusions and thus provides a
      cell protective role by sequestration.

PMID- 21896310
TI  - Prevention of extracellular ADP-induced ATP accumulation of the cultured rat
      spinal astrocytes via P2Y(1)-mediated inhibition of AMPK.
AB  - P2Y(1) is probably an important subtype of purinergic receptors (P2Rs) in
      modulation of the astrocyte activation in spinal cord. The aim of this study was
      to observe the effect of P2Y(1) receptor on the abnormal energy metabolism of the
      cultured rat spinal astrocyte induced by extracellular adenosine diphosphate
      (ADP). The results showed that adenosine triphosphate (ATP) and mitochondrial
      membrane potential (MMP) in the astrocytes were up-regulated in the presence of
      ADP, which could be enhanced by MRS2179, a specific antagonist for P2Y(1)
      receptor. A higher level of expression of the AMP-activated protein kinase (AMPK)
      was found in the presence of MRS2179 and ADP together than that ADP alone.
      Blocking of AMPK with Compound C could effectively inhibit the enhancing effect
      of MRS2179 on ADP-induced astrocyte proliferation and ATP accumulation. Our
      results suggested that the P2Y(1) receptor mediated inhibition of AMPK may help
      to prevent the astrocytes from over activation induced by extracellular ADP.

PMID- 21896311
TI  - Cordycepin decreases activity of hippocampal CA1 pyramidal neuron through
      membrane hyperpolarization.
AB  - Cordycepin (3'-deoxyadenosine) is the main functional component of Cordycepins
      militaris, a renowned traditional Chinese medicine, which has been shown to
      possess anti-tumor, anti-inflammatory, anti-diabetic and neuro-protective
      effects. However, the effect of cordycepin on the central nervous system (CNS)
      remains unclear. In this study, the effects of cordycepin on neuronal activity
      were investigated on the CA1 pyramidal neurons in rat hippocampal brain slices
      using a whole-cell patch clamp technique. Our results revealed that cordycepin
      significantly decreased the frequency of both the spontaneous and evoked action
      potential (AP) firing. While AP spike width, the amplitude of fast after
      hyperpolarization (fAHP), and membrane input resistance were not altered by
      cordycepin, the neuronal membrane potential was hyperpolarized by cordycepin.
      Collectively, these results demonstrate that cordycepin reduces neuronal activity
      by inducing membrane hyperpolarization, indicating that cordycepin may be a
      potential therapeutic strategy for ischemic and other excitotoxic disorders.

PMID- 21896312
TI  - Aquaporins AQP1 and AQP4 in the cerebrospinal fluid of bacterial meningitis
      patients.
AB  - Aquaporins facilitate water transport through cell membranes. Due to the
      localization of AQP1 and AQP4 in the brain, they might contribute to cerebral
      edema. Our study aimed to determine whether AQP1 and AQP4 can be measured in
      cerebrospinal fluid (CSF), and whether there is a difference in AQP1 and AQP4
      concentration between patients with bacterial meningitis (BM) and healthy
      controls. AQP1 and AQP4 concentrations in CSF from 35 patients with BM and 27
      controls were analyzed using a commercial ELISA. The mean concentration of AQP1
      in CSF was significantly elevated in patients with BM (BM: 3.8+/-3.4ng/ml,
      controls: 0.8+/-0.5ng/ml; p<0.001). AQP4 had a tendency to be increased, however
      the difference was not significant (BM: 1.8+/-3.1ng/ml, controls: 0.1+/-0.2ng/ml;
      p=0.092). AQP1 and AQP4 in CSF of BM patients were inversely correlated (r=-0.47,
      p=0.004). We could not find any other correlation between concentration of AQP1
      or AQP4 in CSF and CSF leukocytes, lactate, protein, albumin CSF/serum ratio,
      age, a prediction score, an outcome score or the Glasgow Coma Scale at admission
      in patients with BM. Control patients displayed a correlation between AQP1 and
      the albumin CSF/serum ratio (r=0.390, p=0.040). This is the first study that
      detected AQP1 and AQP4 in CSF. Whether the significant elevation of AQP1 is due
      to a higher expression and subsequent shedding into CSF or a BM-induced cell
      damage needs to be determined.

PMID- 21896313
TI  - Functional polymorphism of the GTP cyclohydrolase 1 gene affects the personality
      trait of novelty seeking in healthy subjects.
AB  - GTP cyclohydrolase 1 (GCH1) is the initial and rate-limiting enzyme in the
      biosynthesis of tetrahydrobiopterin, which is an essential cofactor for
      biosynthetic enzymes of dopamine, serotonin, and nitric oxide. In the present
      study, the association of functional polymorphism of the GCH1 gene (C+243T,
      rs841) with personality traits was examined in 902 healthy Japanese subjects.
      Personality traits were assessed by the Temperament and Character Inventory
      (TCI), and the GCH1 genotype was detected by a PCR-RFLP method. There were no
      significant main effects of the GCH1 genotype on the seven TCI dimension scores,
      but significant interaction effects between the GCH1 genotype and gender were
      found on the scores of novelty seeking. Post-hoc analysis revealed that males
      with the C/C genotype had higher scores of novelty seeking than those with the
      C/T genotype or those with the T/T genotype, while in females the scores of
      novelty seeking were not different among the genotype groups. The present study
      thus suggests that the C+243T polymorphism of the GCH1 gene affects the
      personality trait of novelty seeking in males.

PMID- 21896314
TI  - Novel demonstration of conformationally modified tau in sporadic inclusion-body
      myositis muscle fibers.
AB  - s-IBM is the most common muscle disease of older persons. Its muscle fiber
      molecular phenotype has close similarities to Alzheimer disease (AD) brain,
      including intra-muscle-fiber accumulations of (a) Abeta42 and its oligomers, and
      (b) large, squiggly or linear, clusters of paired-helical filaments (PHFs) that
      are immunoreactive with various antibodies directed against several epitopes of
      phosphorylated tau (p-tau), and thereby strongly resembling neurofibrillary
      tangles of AD brain. In AD brain, conformational changes of tau, including its
      modifications detectable with specific antibodies TG3 (recognizing phosphorylated
      Thr231), and Alz50 and MC1 (both recognizing amino acids 5-15 and 312-322) are
      considered early and important modifications leading to tau's abnormal folding
      and assembly into PHFs. We have now identified conformationally modified tau in
      14 s-IBM muscle biopsies by (a) light-and electron-microscopic
      immunohistochemistry, (b) immunoblots, and (c) dot-immunoblots, using TG3, Alz50
      and MC1 antibodies. Our double-immunolabeling on the light- and electron
      microscopic levels, which combined an antibody against p62 that recognizes s-IBM
      clusters of PHFs, revealed that TG3 immunodecorated, abundantly and exclusively,
      all p62 immunopositive clusters, while Alz50 labeling was less abundant, and MC1
      was mainly diffusely immunoreactive. Interestingly, in the very atrophic
      degenerating fibers, TG3 co-localized with PHF-1 antibody that recognizes tau
      phosphorylated at Ser396/404, which is considered a later change in the formation
      of PHFs; however, most of TG3-positive inclusions in non-atrophic fibers were
      immunonegative with PHF-1. None of the 12 normal- and disease-control muscle
      biopsies contained conformational or PHF-1 immunoreactive tau. This first
      demonstration of conformational tau in s-IBM, because of its abundance in non
      atrophic muscle fibers, suggests that it might play an early role in s-IBM PHFs
      formation and thus be pathogenically important.

PMID- 21896315
TI  - Effect of salicylate on potassium currents in inner hair cells isolated from
      guinea-pig cochlea.
AB  - Although salicylate is one of the most widely used nonsteroidal anti-inflammatory
      drugs, it causes moderate hearing loss and tinnitus at high-dose levels. In the
      present study, salicylate effects on the K currents in inner hair cells were
      examined. Salicylate reversibly reduced the outward K currents (I(K,f)), but did
      not affect the inward current (I(K,n)). Salicylate blocked the outward K currents
      in a concentration-dependent manner according to Hill equation with a half
      blocking concentration of 1.66mM, and the Hill coefficient of 1.86.

PMID- 21896316
TI  - Protective effects of resveratrol through the up-regulation of SIRT1 expression
      in the mutant hSOD1-G93A-bearing motor neuron-like cell culture model of
      amyotrophic lateral sclerosis.
AB  - Resveratrol has recently been widely reported to be an age-delaying and
      neuroprotective compound, and it appears to produce these benefits by activating
      silent mating type information regulation 2 homolog 1 (SIRT1). However, the role
      that SIRT1 activation plays in the pathogenesis of amyotrophic lateral sclerosis
      (ALS) remains unclear. In the present study, SIRT1 expression was found to be
      much lower in the mutant hSOD1G93A-bearing VSC4.1 cells compared to hSOD1wt cells
      when both were cultured in low-serum medium, indicating the involvement of SIRT1
      activation defects in the pathogenesis of ALS under energetic stress. Further
      investigation revealed that a 24-h treatment with 0.5-20MUM resveratrol had a
      dose-dependent protective effect on this ALS cell model, and the effects of
      resveratrol on increasing cell viability, preventing cell apoptosis and elevating
      cellular ATP levels through promoting mitochondria biogenesis were blocked by
      SIRT1 inhibition. This further demonstrated a role for SIRT1 activation in the
      protection of neuronal cells from degeneration. These findings suggest that
      resveratrol can protect the ALS cell model from mutant SOD1-mediated toxicity
      through up-regulating the expression of SIRT1, which represents a potential
      therapeutic target for preventing the motor neuron degeneration in ALS patients.

PMID- 21896317
TI  - CRIP1a switches cannabinoid receptor agonist/antagonist-mediated protection from
      glutamate excitotoxicity.
AB  - A shared pathology among many neurological and neurodegenerative disorders is
      neuronal loss. Cannabinoids have been shown to be neuroprotective in multiple
      systems. However, both agonists and antagonists of the CB(1) cannabinoid receptor
      are neuroprotective, but the mechanisms responsible for these actions remain
      unclear. Recently a CB(1) receptor interacting protein, CRIP1a, was identified
      and found to alter CB(1) activity. Here we show that in an assay of glutamate
      neurotoxicity in primary neuronal cortical cultures CRIP1a disrupts agonist
      induced neuroprotection and confers antagonist-induced neuroprotection.

PMID- 21896318
TI  - Developmental localization of NMDA receptors, Src and MAP kinases in mouse brain.
AB  - Activation of NMDA receptors (NMDAR) is associated with divergent downstream
      signaling leading to neuronal survival or death that may be regulated in part by
      whether the receptor is located synaptically or extrasynaptically. Distinct
      activation of the MAP kinases ERK and p38 by synaptic and extrasynaptic NMDAR is
      one of the mechanisms underlying these differences. We have recently shown that
      the Src family kinases (SFKs) play an important role in neonatal hypoxic-ischemic
      brain injury by regulating NMDAR phosphorylation. In this study, we characterized
      the distribution of NMDAR, SFKs and MAP kinases in synaptic and extrasynaptic
      membrane locations in the postnatal day 7 and adult mouse cortex. We found that
      the NMDAR, SFKs and phospho-NR2B were predominantly at synapses, whereas striatal
      enriched protein tyrosine phosphatase (STEP) and its substrates ERK and p38 were
      much more concentrated extrasynaptically. NR1/NR2B was the main subunit at
      extrasynaptic membrane with concomitant NR2B phosphorylation at tyrosine (Y) 1336
      in the immature brain. STEP expression increased, while p38 decreased with
      development in the extrasynaptic membrane. These results suggest that SFKs and
      STEP are poised to differentially regulate NMDAR-mediated signaling pathways due
      to their distinct subcellular localization, and thus may contribute to the age
      specific differences seen in vulnerability, pathology and consequences of hypoxic
      ischemic brain injury.

PMID- 21896319
TI  - Psychosocial environment and health: methodological variability of the salivary
      cortisol measurements.
AB  - Salivary cortisol offers a novel approach to understand the relationship between
      psychosocial environment and health. This study examines the intra-individual
      relationships among indicators of the cortisol circadian rhythm and investigates
      the influence of determinants affecting the day-to-day variability of the
      cortisol measures. Over three weekdays, 87 healthy subjects (63 females and 24
      males) collected saliva samples at seven time points to assess the cortisol
      awakening response (CAR), and to evaluate the post morning cortisol profile. The
      generalized estimating equations method was used to explore the relations between
      repeated cortisol measures and potential determinants (sociodemographic, health,
      and sampling factors) influencing salivary cortisol levels. Younger age, being
      smoker, and sampling on a working day were associated with higher at awakening
      and total cortisol excretion in the morning period. Higher overall cortisol
      excretion and cortisol increase in the first hour of the day were found for
      adherents to sampling procedure. Higher educational level was found associated
      with greater total cortisol excretion in the morning and post morning period,
      while a flatter diurnal slope was found in smokers. Results are consistent with
      the knowledge that the circadian cortisol rhythm is differentially determined by
      situational factors and that results obtained in the early morning hour are of
      crucial importance corroborating the evidence that the CAR is a highly state
      dependent phenomenon. These data indicate that many confounding factors need to
      be controlled when using salivary cortisol as biomarker of the mind-health
      interrelationship.

PMID- 21896320
TI  - Alcohol enhanced permeation in model membranes. Part II. Thermodynamic analysis
      of membrane partitioning.
AB  - The role of solvents in drug transport has not been properly addressed in the
      literature, despite its well known influence on drug permeation. Previously we
      have conducted thermodynamic and kinetic analyses to probe the molecular
      mechanisms of alcohol enhanced permeation. In the present study, the influence of
      temperature on the partitioning of methyl paraben into silicone membranes is
      investigated. In line with previous membrane transport studies of methyl paraben
      in silicone membranes, butanol and heptanol are used as representative alcohols.
      The results show higher amounts of methyl paraben extracted from the silicone
      membrane following equilibration with butanol, at all experimental temperatures.
      This was in line with alcohol uptake data. In fact, a linear correlation (r(2)
      ~0.97) was found between the amount of methyl paraben in the silicone membrane
      and the corresponding alcohol uptake. Calculated "specific" vehicle-membrane
      partition coefficients for both alcohols were approximately one, suggesting that
      the effective concentrations of methyl paraben inside and outside the membrane
      were the same. Thermodynamic analysis of the alcohol-membrane partition
      coefficients as a function of temperature showed no apparent trend for butanol,
      with an associated enthalpy change of approximately zero. Conversely, there was a
      positive trend in the van't Hoff plot for methyl paraben in heptanol, indicative
      of an exothermic process. Moreover, the partitioning trends of methyl paraben in
      silicone membranes obtained from membrane transport and equilibrium experiments
      were not the same. This reflects the fundamental differences between the
      calculated vehicle-membrane partition coefficients in the two studies. Finally,
      the findings from membrane transport and equilibrium experiments support a model
      of alcohol enhanced permeation where high solvent sorption promotes high solute
      concentrations in the overall volume of the membrane (i.e. K), thus leading to
      modified solute transport (i.e. increased flux). The same model also accounts for
      changes in membrane diffusivity (i.e. D) related to the properties of the imbibed
      alcohol.

PMID- 21896321
TI  - Thermo-responsive shell cross-linked PMMA-b-P(NIPAAm-co-NAS) micelles for drug
      delivery.
AB  - Thermo-responsive amphiphilic poly(methyl methacrylate)-b-poly(N
      isopropylacrylamide-co-N-acryloxysuccinimide) (PMMA-b-P(NIPAAm-co-NAS)) block
      copolymer was synthesized by successive RAFT polymerizations. The uncross-linked
      micelles were facilely prepared by directly dissolving the block copolymer in an
      aqueous medium, and the shell cross-linked (SCL) micelles were further fabricated
      by the addition of ethylenediamine as a di-functional cross-linker into the
      micellar solution. Optical absorption measurements showed that the LCST of
      uncross-linked and cross-linked micelles was 31.0 degrees C and 40.8 degrees C,
      respectively. Transmission electron microscopy (TEM) showed that both uncross
      linked and cross-linked micelles exhibited well-defined spherical shape in
      aqueous phase at room temperature, while the SCL micelles were able to retain the
      spherical shape with relatively smaller dimension even at 40 degrees C due to the
      cross-linked structure. In vitro drug release study demonstrated a slower and
      more sustained drug release behavior from the SCL micelles at high temperature as
      compared with the release profile of uncross-linked micelles, indicating the
      great potential of SCL micelles developed herein as novel smart carriers for
      controlled drug release.

PMID- 21896322
TI  - Spasmolytic activity of Rosmarinus officinalis L. involves calcium channels in
      the guinea pig ileum.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Rosmarinus officinalis L. is a plant used around
      the world for its properties to cure pain in several conditions, such as
      arthritic and abdominal pain or as an antispasmodic; however, there are no
      scientific studies demonstrating its spasmolytic activity. Therefore, the aim of
      the present study was to investigate the effect of an ethanol extract from
      Rosmarinus officinalis aerial parts and the possible mechanism involved by using
      rings from the isolated guinea pig ileum (IGPI). MATERIALS AND METHODS: The IGPI
      rings were pre-contracted with potassium chloride (KCl; 60 mM), acetylcholine
      (ACh; 1 * 10(-9) to 1 * 10(-5)M) or electrical field stimulation (EFS; 0.3 Hz of
      frequency, 3.0 ms of duration and 14 V intensity) and tested in the presence of
      the Rosmarinus officinalis ethanol extract (150, 300, 600 and 1 200 MUg/mL) or a
      referenced smooth muscle relaxant (papaverine, 30 MUM). In addition, the possible
      mechanism of action was analyzed in the presence of hexametonium (a ganglionic
      blocker), indomethacine (an inhibitor of prostaglandins), l-NAME (a selective
      inhibitor of the nitric oxide synthase) and nifedipine (a calcium channel
      blocker). RESULTS: Rosmarinus officinalis ethanol extract exhibited a significant
      and concentration-dependent spasmolytic activity on the contractions induced by
      KCl (CI(50) = 661.06 +/- 155.91 MUg/mL); ACh (CI(50) = 464.05 +/- 16.85 MUg/mL)
      and EFS (CI(50) = 513.72 +/- 34.13 MUg/mL). Spasmolytic response of Rosmarinus
      officinalis (600 MUg/mL) was reverted in the presence of nifedipine 1 MUM, but
      not in the presence of hexamethonium 0.5mM, indomethacine 1 MUM or L-NAME 100
      MUM. CONCLUSION: The present results reinforce the use of Rosmarinus officinalis
      as antispasmodic in folk medicine. Moreover, it is demonstrated the involvement
      of calcium channels in this activity, but not the participation of nicotinic
      receptors, prostaglandins or nitric oxide.

PMID- 21896323
TI  - Antigenotoxic and antioxidant activities of palmarosa and citronella essential
      oils.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Essential oils of palmarosa and citronella have
      been extensively used in ancient Indian and South-east Asian traditional
      medicines. AIM OF THE STUDY: These essential oils have been reported to exhibit
      antimicrobial, anti parasitic effects against bacteria, yeasts, filamentous
      fungi, and viruses. In the present study the oils were tested for their potential
      antigenotoxic and antioxidant properties in human lymphocyte cells. MATERIALS AND
      METHODS: The antigenotoxic effect on human lymphocyte cells (measurement of cell
      viability, DNA damage) was studied using trypan blue dye exclusion test, plasmid
      pBR322 DNA strand scission, and comet assay. Anti-oxidant activity was evaluated
      by DPPH(+) free radical scavenging and lipid peroxidation assay. RESULTS: The
      essential oils showed a good antigenotoxic activity against methyl
      methanesulphonate (MMS) and hydrogen peroxide. In addition, a significant dose
      dependent antioxidant activity was observed. CONCLUSION: Our data provide
      evidence that support the usage of palmarosa and citronella essential oils in
      traditional herbal preparations. They can constitute a natural source of a new
      and safe antioxidant.

PMID- 21896324
TI  - An integrative approach of linking traditional Chinese medicine pattern
      classification and biomedicine diagnosis.
AB  - Traditional Chinese medicine (TCM) is a medical system with over 3000 years of
      continuous practice experience and refinement through treatment observations. The
      TCM pattern classification (also defined as Syndrome or Zheng differentiation)
      and treatment of ill health is the basis and the key concept of the TCM theory.
      All diagnostic and therapeutic methods in TCM are based on the differentiation of
      TCM pattern. TCM pattern can be considered as the TCM theoretical interpretation
      of the symptom profiles. Pattern classification is often used as a guideline in
      disease classification in TCM practice and has been recently incorporated with
      biomedical diagnosis, resulting in the increasing research interest of TCM
      pattern among various disciplines of integrative medicine. This paper describes
      the historical evolution on the integration of the TCM pattern classification and
      disease diagnosis in biomedicine, the methodology of pattern classification for
      diseases, efficacy of TCM practice with integration of TCM pattern classification
      and biomedical disease diagnosis, and the biological basis of TCM pattern. TCM
      pattern classification, which may lead to new findings in biological sciences,
      was also discussed.

PMID- 21896325
TI  - Age-related changes in fatty acid profile and locomotor activity rhythms in
      Nothobranchius korthausae.
AB  - The life cycle of Nothobranchius korthausae, a Cyprinodontiformes fish, was
      studied in our laboratory to characterise the ageing process. Some morphological
      changes, such as spine curvature, skin colour, and fin and eye appearance are
      described. Growth and survival curves reflected a fast life cycle with rapid
      initial growth until 4weeks of age, after which the fish grew more slowly before
      reaching their final size in week 40. Senescence onset was established at week 48
      with a decrease in spawn size and viability and a general decline in the animal's
      appearance (weight and colouration losses, caudal fin degradation, and
      cataractogenesis). The fatty acid composition changed with age, with high
      unsaturation in the adult stage as reflected by a high peroxidation index, a
      condition that is associated with high susceptibility to oxidative damage if
      elevated reactive oxygen species (ROS) production occurs. Senescent fish had an
      increase in monounsaturated fatty acid proportions and a lower peroxidation index
      (226.5+/-19.7 in adults versus 120.2+/-19.1 in senescent fish, P<0.05). The
      circadian system, as reflected by locomotor activity rhythms, showed noticeable
      changes with age. Twenty-four-week-old fish (adults) had a robust diurnal rhythm
      that showed a decrease in total activity, an increase in rhythm fragmentation,
      and a fall in amplitude and regularity with age. Changes were clearly reflected
      in the Circadian Function Index variations (0.56, 0.47 and 0.25 at 24, 48 and
      72weeks of age, respectively). In conclusion, N. korthausae appears to be a
      species with appropriate characteristics for ageing studies because it manifests
      clear signs of progressive ageing. Comparing species of Nothobranchius genus with
      different lifespans may be useful for increasing our understanding of the ageing
      process.

PMID- 21896327
TI  - The role of reactive oxygen species in WP 631-induced death of human ovarian
      cancer cells: a comparison with the effect of doxorubicin.
AB  - In the present study, we investigated the anticancer activity of WP 631, a new
      anthracycline analog, in weakly doxorubicin-resistant SKOV-3 ovarian cancer
      cells. We studied the time-course of apoptotic and necrotic events: the
      production of reactive oxygen species (ROS) and changes in the mitochondrial
      membrane potential in human ovarian cancer cells exposed to WP 631 in the
      presence and absence of an antioxidant, N-acetylcysteine (NAC). The effect of WP
      631 was compared with the activity of doxorubicin (DOX), the best known first
      generation anthracycline. Cytotoxic activity was determined by the MTT assay. The
      morphological changes characteristic of apoptosis and necrosis in drug-treated
      cells were analyzed by double staining with Hoechst 33258 and propidium iodide
      (PI) using fluorescence microscopy. The production of reactive oxygen species and
      changes in mitochondrial membrane potential were studied using specific
      fluorescence probes: DCFH2-DA and JC-1, respectively. The experiments showed that
      WP 631 was three times more cytotoxic than DOX in the tested cell line. It was
      found that the new anthracycline analog induced mainly apoptosis and, marginally,
      necrosis. Apoptotic cell death was associated with morphological changes and a
      decrease in mitochondrial membrane potential. In comparison to DOX, the novel
      bisanthracycline induced a significantly higher level of ROS and a greater drop
      in the membrane potential. The results provide direct evidence that the novel
      anthracycline WP 631 is considerably more cytotoxic to human SKOV-3 ovarian
      cancer cells than doxorubicin. The drug can produce ROS, which are immediately
      involved in the induction of apoptotic cell death.

PMID- 21896328
TI  - MRI evaluation of the antitumor activity of paramagnetic liposomes loaded with
      prednisolone phosphate.
AB  - The design of long circulating liposomes co-loaded with the glucocorticoid
      prednisolone phosphate (PLP) and the amphiphilic paramagnetic contrast agent Gd
      DOTAMA(C(18))(2) allowed the MRI-guided in vivo visualization of the delivery and
      biodistribution of PLP, as well as the monitoring of drug efficacy. The
      performance of this theranostic probe was investigated in a mouse model bearing a
      melanoma B16 syngeneic tumor. The release kinetics of the drug were evaluated in
      vitro where it displayed a peculiar behavior characterized by a fast process
      (completed in few hours) involving only a small portion (<5%) of the drug.
      Interestingly, the incorporation of the amphiphilic imaging reporter in the
      liposomal bilayer slightly increased the amount of the fast-release portion
      (<10%), thus suggesting that it could be attributed to a drug fraction embedded
      in the liposomal bilayer. In fact, the release of a hydrophilic imaging probe
      encapsulated in the inner core of the same long circulating liposomes formulated
      for carrying the drug, displayed different, single-step, kinetics. The in vivo
      monitoring of the antitumor activity of the nanomedicine revealed that the
      incorporation of the MRI probe into the liposome bilayer did not significantly
      affect the drug efficacy. The in vivo experiments also indicated a relevant and
      fast liposome uptake from macrophage-rich organs like spleen and liver, which
      reduced the tumor accumulation of the liposomes. The accumulation of the
      amphipatic MRI label caused the occurrence of a long-term residual T(1) contrast
      still detectable 1week after injection.

PMID- 21896326
TI  - Absence of phagocyte NADPH oxidase 2 leads to severe inflammatory response in
      lungs of mice infected with Coccidioides.
AB  - Production of reactive oxygen species (ROS) resulting from phagocytic NADPH
      oxidase (NOX2) activity has been reported to contribute to host defense against
      numerous microbial pathogens. In this study we explored the role of NOX2
      production in experimental coccidioidomycosis, a human respiratory disease caused
      by a soil-borne fungal pathogen. Activated and non-activated macrophages isolated
      from either NOX2(-/-) knock-out or wild type (WT) mice showed comparable ROS
      production and killing efficiency in vitro when infected with parasitic cells of
      Coccidioides. Both mouse strains also revealed similar fungal burden in their
      lungs and spleen at 7 and 11 days after intranasal challenge with Coccidioides
      spores, although the NOX2(-/-) mice died earlier than the WT strain. Immunization
      of the NOX2(-/-) and WT mice with a live, attenuated vaccine strain of
      Coccidioides also resulted in comparable reduction of the fungal burden in both
      lungs and spleen. These combined results initially suggested that NOX2 activity
      and ROS production are not essential for protection against Coccidioides
      infection. However, the reduced survival of non-vaccinated NOX2(-/-) mice
      correlated with high, sustained numbers of lung-infiltrated neutrophils on days 7
      and 11 postchallenge, an expansion of the regulatory T cell population in
      infected lungs in the knock-out mice, and elevated concentrations of pro
      inflammatory cytokines and chemokines in lung homogenates compared to infected WT
      mice. Although NOX2-derived ROS appeared to be dispensable for both innate and
      acquired immunity to pulmonary Coccidioides infection, evidence is presented that
      NOX2 production plays a role in limiting pathogenic inflammation in this murine
      model of coccidioidomycosis.

PMID- 21896329
TI  - Inhibitory effect of siRNA complexes with polyamidoamine dendrimer/alpha
      cyclodextrin conjugate (generation 3, G3) on endogenous gene expression.
AB  - In the present study, we prepared the small interfering RNA (siRNA) complexes
      with polyamidoamine (PAMAM) dendrimer (G3) conjugate with alpha-cyclodextrin
      (alpha-CDE (G3)), and examined the physicochemical properties, serum resistance,
      in vitro RNAi effects on endogenous gene expression, cytotoxicity, interferon
      response, hemolytic activity, cellular association and intracellular
      distribution. In addition, these results were compared to the siRNA complexes
      with the commercial transfection reagents such as linear polyethyleneimine (PEI),
      LipofectamineTM2000 (L2) and RNAiFectTM (RF). alpha-CDE (G3) interacted with
      siRNA, and suppressed siRNA degradation by serum. The siRNA complex with alpha
      CDE (G3) showed the potent RNAi effects against Lamin A/C and Fas expression with
      negligible cytotoxicity and hemolytic activity, compared to those of the
      transfection reagents in Colon-26-luc cells and NIH3T3-luc cells. Cell-death
      patterns induced by siRNA polyplexes with alpha-CDE (G3) and PEI were different
      from siRNA lipoplexes with L2 and RF. alpha-CDE (G3) delivered fluorescent
      labeled siRNA to cytoplasm, not nucleus, after transfection in NIH3T3-luc cells.
      Taken together, alpha-CDE (G3) could be potentially used as a siRNA carrier to
      provide the RNAi effect on endogenous gene expression with negligible
      cytotoxicity.

PMID- 21896330
TI  - Fabrication of quercetin nanocrystals: comparison of different methods.
AB  - The main aim of this study was to prepare quercetin nanocrystals using three
      fabrication methods, viz. high-pressure homogenization, bead milling, and cavi
      precipitation. The three fabrication methods were compared in terms of particle
      size, saturation solubility, and dissolution of the products obtained. The
      average particle size of the coarse quercetin was 50.1 MUm. The three methods
      produced quercetin particles in the nanometre range (276-787 nm) and the smallest
      nanocrystals of around 276.7 nm were fabricated by bead milling. The particle
      size, polydispersity index, zeta potential, and saturation solubility values for
      the products fabricated by both high-pressure homogenization and bead mill were
      similar and thus both represented an efficient means to fabricate quercetin
      nanosuspensions. According to X-ray diffraction analysis, all nanocrystals were
      still in the crystalline state after being fabricated by the three methods. The
      cavi-precipitated product exhibited larger particle size and did not show an
      optimum stability as suggested by the zeta potential values. However, cavi
      precipitated quercetin nanosuspension showed the higher saturation solubility due
      to the presence of ethanol. The bead milled products with the lowest particle
      size exhibited a saturation solubility of 25.59 +/- 1.11 MUg/ml, approximately
      nine times higher than coarse quercetin. Overall, the dissolution rates of the
      quercetin nanosuspensions fabricated by these three methods enhanced compared to
      the coarse quercetin.

PMID- 21896331
TI  - Formation of diethylstilbestrol-DNA adducts in human breast epithelial cells and
      inhibition by resveratrol.
AB  - Extensive evidence exists that the reaction of estrogen metabolites with DNA
      produces depurinating adducts that, in turn, induce mutations and cellular
      transformation. While it is clear that these estrogen metabolites result in a
      neoplastic phenotype in vitro, further evidence supporting the link between
      estrogen-DNA adduct formation and its role in neoplasia induction in vivo would
      strengthen the evidence for a genotoxic mechanism. Diethylstilbestrol (DES), an
      estrogen analogue known to increase the risk of breast cancer in women exposed in
      utero, is hypothesized to induce neoplasia through a similar genotoxic mechanism.
      Cultured MCF-10F human breast epithelial cells were treated with DES at varying
      concentrations and for various times to determine whether the addition of DES to
      MCF-10F cells resulted in the formation of depurinating adducts. This is the
      first demonstration of the formation of DES-DNA adducts in human breast cells. A
      dose-dependent increase in DES-DNA adducts was observed. Demonstrating that
      treatment of MCF-10F cells with DES, a known human carcinogen, yields
      depurinating adducts provides further support for the involvement of these
      adducts in the induction of breast neoplasia. Previous studies have demonstrated
      the ability of antioxidants such as resveratrol to prevent the formation of
      estrogen-DNA adducts, thus preventing a key carcinogenic event. In this study,
      when MCF-10F cells were treated with a combination of resveratrol and DES, a dose
      dependent reduction in the level of DES-DNA adducts was also observed.

PMID- 21896332
TI  - RGS4 exerts inhibitory activities on the signaling of dopamine D2 receptor and D3
      receptor through the N-terminal region.
AB  - Dopamine D(2) receptor and D(3) receptor (D(2)R and D(3)R) are the major targets
      for current antipsychotic drugs, and their proper regulation has pathological and
      pharmacological significance. This study was conducted to understand the
      functional roles and molecular mechanisms of RGS proteins (RGS2, RGS4, and RGS9
      2) on the signaling of D(2)R and D(3)R. RGS proteins were co-expressed with D(2)R
      and D(3)R in HEK-293 cells. The protein interactions between RGS proteins and
      D(2)R/D(3)R, and effects of RGS proteins on the internalization, signaling, and
      desensitization of D(2)R/D(3)R were determined. In addition, the RGS4 proteins
      were subdivided into N-terminal region, RGS domain, and the C-terminal region,
      and the specific subdomain of RGS4 protein involved in the regulation of the
      signaling of D(2)R/D(3)R was determined. All of RGS proteins we tested interacted
      with D(2)R/D(3)R. RGS4 exerted potent inhibitory activities on the signaling of
      D(2)R/D(3)R. RGS9-2 exerted selective but moderate inhibitory activity on D(3)R
      and the internalization of D(2)R. RGS2 had no effect. The N-terminal domain of
      RGS4 was involved in its interaction with D(2)R and D(3)R and was required for
      the inhibitory activity of the RGS domain. The study for the first time showed
      that RGS4 is the major RGS protein which interacts through the N-terminal region
      and exerts potent inhibitory activities on the signaling of D(2)R and D(3)R.

PMID- 21896333
TI  - Intracellular localisation and innate immune responses following Francisella
      noatunensis infection of Atlantic cod (Gadus morhua) macrophages.
AB  - The facultative intracellular bacterium Francisella noatunensis causes
      francisellosis in Atlantic cod (Gadus morhua), but little is known about its
      survival strategies or how these bacteria evade the host immune response. In this
      study we show intracellular localisation of F. noatunensis in cod macrophages
      using indirect immunofluorescence techniques and green fluorescent labelled
      bacteria. Transmission electron microscopy revealed that F. noatunensis was
      enclosed by a phagosomal membrane during the initial phase of infection. Bacteria
      were at a later stage of the infection found in large electron-lucent zones,
      apparently surrounded by a partially intact or disintegrated membrane. Immune
      electron microscopy demonstrated the release of bacterial derived vesicles from
      intracellular F. noatunensis, an event suspected of promoting phagosomal membrane
      degradation and allowing escape of the bacteria to cytoplasm. Studies of
      macrophages infected with F. noatunensis demonstrated a weak activation of the
      inflammatory response genes as measured by increased expression of the
      Interleukin (IL)-1beta and IL-8. In comparison, a stronger induction of gene
      expression was found for the anti-inflammatory IL-10 indicating that the
      bacterium exhibits a role in down-regulating the inflammatory response.
      Expression of the p40 subunit of IL-12/IL-17 genes was highly induced during
      infection suggesting that F. noatunensis promotes T cell polarisation. The host
      macrophage responses studied here showed low ability to distinguish between live
      and inactivated bacteria, although other types of responses could be of
      importance for such discriminations. The immunoreactivity of F. noatunensis
      lipopolysaccharide (LPS) was very modest, in contrast to the strong capacity of
      Escherichia coli LPS to induce inflammatory responsive genes. These results
      suggest that F. noatunensis virulence mechanisms cover many strategies for
      intracellular survival in cod macrophages.

PMID- 21896334
TI  - Female children with autism spectrum disorder: an insight from mass-univariate
      and pattern classification analyses.
AB  - Several studies on structural MRI in children with autism spectrum disorders
      (ASD) have mainly focused on samples prevailingly consisting of males. Sex
      differences in brain structure are observable since infancy and therefore caution
      is required in transferring to females the results obtained for males. The
      neuroanatomical phenotype of female children with ASD (ASDf) represents indeed a
      neglected area of research. In this study, we investigated for the first time the
      anatomic brain structures of a sample entirely composed of ASDf (n=38; 2-7 years
      of age; mean=53 months; SD=18) with respect to 38 female age and non verbal IQ
      matched controls, using both mass-univariate and pattern classification
      approaches. The whole brain volumes of each group were compared using voxel-based
      morphometry (VBM) with diffeomorphic anatomical registration through
      exponentiated lie algebra (DARTEL) procedure, allowing us to build a study
      specific template. Significantly more gray matter (GM) was found in the left
      superior frontal gyrus (SFG) in ASDf subjects compared to controls. The GM
      segments obtained in the VBM-DARTEL preprocessing are also classified with a
      support vector machine (SVM), using the leave-pair-out cross-validation protocol.
      Then, the recursive feature elimination (SVM-RFE) approach allows for the
      identification of the most discriminating voxels in the GM segments and these
      prove extremely consistent with the SFG region identified by the VBM analysis.
      Furthermore, the SVM-RFE map obtained with the most discriminating set of voxels
      corresponding to the maximum Area Under the Receiver Operating Characteristic
      Curve (AUC(max)=0.80) highlighted a more complex circuitry of increased cortical
      volume in ASDf, involving bilaterally the SFG and the right temporo-parietal
      junction (TPJ). The SFG and TPJ abnormalities may be relevant to the
      pathophysiology of ASDf, since these structures participate in some core atypical
      features of autism.

PMID- 21896335
TI  - Uncovering cryptic species diversity of a termite community in a West African
      savanna.
AB  - To uncover the termite species diversity of a natural African savanna ecosystem,
      we combined morphological analyses and sequencing of three gene fragments
      (cytochrome oxidase I, cytochrome oxidase II and 28SrDNA, total length about 2450
      bp) to infer putative species from phylogenetic trees. We identified 18 putative
      species clusters with high support values and which we retrieved consistently.
      Samples from two genera (Ancistrotermes and Microcerotermes) were excluded from
      the mitochondrial phylogenetic analyses as they might represent nuclear
      mitochondrial sequences (NUMTs). In total, our data suggest a species richness of
      at least 20 species, all but one belonging to the Termitidae (higher termites),
      and among them the fungus-growing Macrotermitinae were most prevalent with at
      least nine putative species. Within the fungus-growers the most species-rich
      genus was Microtermes and its four putative species were all cryptic species.
      Their abundance in the samples suggests that they play an important ecological
      role which is completely unstudied also due to the lack of reliable
      identification means. Our study shows that morphological traits are unreliable
      means of species identification for several termite taxa. Yet reliable and
      consistent identification is necessary for studying the functional role of
      termites in ecosystem and global processes.

PMID- 21896336
TI  - Vibrio cholerae O1 lineages driving cholera outbreaks during seventh cholera
      pandemic in Ghana.
AB  - In recent years, the frequency of cholera epidemics across Africa has increased
      significantly with thousands of people dying each year. However, there still
      exists a lack of information concerning the Vibrio cholerae O1 lineages driving
      early and contemporary epidemics since the seventh cholera pandemic started in
      the continent. This compromises the understanding of the forces determining the
      epidemiology of cholera in Africa and its control. This study aimed to analyze a
      collection of V. cholerae O1 strains from the beginning of the seventh cholera
      pandemic in Ghana and to compare them with recent isolates to understand the
      evolution of the cholera epidemic in Ghana. V. cholerae O1 strains were
      characterized by means of Multilocus Sequence Analysis (MLSA), genes from the
      virulence core genome (VCG), and genes related to the choleragenic phenotype. Our
      results revealed two major clusters of Ghanaian V. cholerae O1 strains, El Tor
      and Amazonia/Ghana. Concerning the virulence genes, all strains harbored the set
      of VCG and most were positive for VSP-II genomic island. The ctxB gene of the
      contemporary strains was characterized as Altered El Tor. The strains from 1970
      to 1980 were susceptible to all antibiotics tested, except for the Amazonia/Ghana
      cluster that was resistant to aminoglycosides and carried the class 2 integron
      with the sat2-aadA1 arrangement. This study showed that distinct V. cholerae O1
      were the determinants of cholera outbreaks in Ghana. Thus, in endemic regions,
      such as Africa, cholera can be caused by various V. cholerae O1 genotypes.

PMID- 21896337
TI  - Mycobacterium tuberculosis complex detection in human remains: tuberculosis
      spread since the 17th century in Rio de Janeiro, Brazil.
AB  - Paleogenetic analysis for tuberculosis (TB) was conducted on bone and sediment
      samples dating from the 17th to 19th centuries from the archeological site of
      Nossa Senhora do Carmo Church in Rio de Janeiro, Brazil. Forty samples were
      analyzed, corresponding to 32 individuals from 28 burials, 22 of primary type and
      6 of secondary type. The samples were collected following strict paleogenetic
      investigation guidelines and submitted to ancient DNA (aDNA) extraction. In order
      to detect TB infection, aDNA hybridizations with the molecular targets of
      Mycobacterium tuberculosis complex (MTC) IS6110 and IS1081 were applied.
      Additionally, the ancestry of individuals was assessed by human mitochondrial DNA
      (mtDNA) analysis of hypervariable segment I (HVS-I) sequence polymorphisms. The
      results of aDNA hybridizations demonstrated varying levels of MTC intensity in
      17/32 individuals (53.1%), using the IS6110 target. The IS1081 MTC target showed
      lower sensitivity, confirming TB positivity in 10/32 (31.2%) individuals. The
      mtDNA analysis allowed the recovery of HVS-I sequences in 23/32 individuals
      (71.8%). The majority of these individuals (21/23, 91.3%) were of European
      ancestry, especially in primary burials. Haplogroups U, J, V, T, K, N, H and R,
      were identified with haplogroup U being the most frequent at 6/23 (26.1%).
      African and Amerindian mtDNA haplogroups were observed in two individuals in
      secondary burials. In spite of the ecclesiastic and aristocratic bias of the
      population of the study, human ancestry analysis revealed the prominent
      contribution of Europeans in the introduction or spread of TB in the New World.

PMID- 21896338
TI  - Multiple amino acid substitutions involved in enhanced pathogenicity of LPAI H9N2
      in mice.
AB  - Human infection of avian influenza H9N2 virus highlighted the need to better
      understand the mechanism of interspecies transmission. In this study, we
      generated mouse-adapted influenza virus (ma01) through serial lung-to-lung
      passages of a wild-type H9N2 (A/chicken/Hubei/01/1999). Ma01 caused highly lethal
      infection in mice with severe lung pathology and extended tissue tropism. Nine
      amino acid substitutions of ma01 were observed in five viral genes (those for
      PB2, PA, NA, M1, and NS1). Of these mutations, substitutes of PB2(627), PA(349),
      PA(605), NA(88), and NA(356) were absent in influenza H9N2. Furthermore, the
      targets of wild-type virus responding to mouse microRNA mmu-mir-1940 and mmu-mir
      1904 were eliminated in ma01. The mutation PB2(627) of ma01 confirmed as a key
      virulence determinant of influenza H5N1 was responsible for the altered
      recognition of mmu-mir-1904. In addition, induction of IL-1beta, IL-6, TNF-alpha,
      and IFN-beta was found in significantly higher levels in ma01 infected mouse
      peripheral blood than parental strain. These results demonstrate that multiple
      amino acid substitutions and avoidance of microRNA recognitions may be essential
      for lethal infection and high speed of virus growth can outcompete the antiviral
      response of infected host.

PMID- 21896339
TI  - Prevention of FGF-2-induced angiogenesis by scopoletin, a coumarin compound
      isolated from Erycibe obtusifolia Benth, and its mechanism of action.
AB  - Previous work in our laboratory has shown that scopoletin, one of the main
      bioactive constituents of Erycibe obtusifolia Benth stems, exerts anti-arthritic
      activity in vivo partly by preventing synovial angiogenesis. The present study
      was performed to further investigate the anti-angiogenic potential of scopoletin,
      focusing on the mechanisms of action in vitro. In the aortic ring sprouting
      assay, scopoletin (10, 30 and 100 MUM) significantly inhibited the growth of
      endothelial sprouts in a concentration-dependent manner. As to human umbilical
      vein endothelial cells (HUVECs), scopoletin could inhibit their proliferation,
      migration and tubule formation induced by FGF-2, especially the proliferation. It
      also remarkably decreased the expression of VEGF at mRNA and protein levels, and
      the phosphorylations of IKKalpha and IkappaB but not Akt, as well as the
      degradation of IkappaB caused by FGF-2 in HUVECs. These findings suggest that
      scopoletin is substantially able to attenuate FGF-2-induced angiogenesis, and it
      might act by directly preventing the stimulation action of FGF-2 and by
      indirectly decreasing the production of VEGF. Scopoletin down-regulated the VEGF
      expression through NF-kappaB rather than PI-3K/Akt signaling pathway.

PMID- 21896341
TI  - Cholera vaccines: not live.

PMID- 21896342
TI  - Vaccination in paediatric patients with auto-immune rheumatic diseases: a
      systemic literature review for the European League against Rheumatism evidence
      based recommendations.
AB  - OBJECTIVES: To analyze available evidence on vaccinations in paediatric patients
      with rheumatic and autoinflammatory diseases. This evidence formed the basis of
      the recently constructed European League against Rheumatism (EULAR)
      recommendations for vaccination of these patients. METHODS: A systematic
      literature review in the MEDLINE and EMBASE databases was conducted using various
      terms for vaccinations, paediatric rheumatic and autoinflammatory diseases and
      immunosuppressive drugs. Only papers on paediatric patients (<18 years of age)
      were selected. A panel of 13 experts in the field graded methodological quality
      and extracted data using predefined criteria. RESULTS: 27 papers were available.
      No studies were found on autoinflammatory diseases. 14 studies considered live
      attenuated vaccines. Evidence so far supports the safety and immunogenicity of
      non-live composite vaccines, although studies were underpowered to accurately
      assess safety. Live-attenuated vaccines did not cause disease flares or severe
      adverse events, not even in patients on methotrexate and low dose
      glucocorticosteroids. Seven patients on anti-TNFalpha therapy were described
      receiving the live-attenuated measles, mumps, rubella (n=5) or varicella (n=2)
      booster without severe adverse events. CONCLUSIONS: Data on safety and efficacy
      of vaccinations in paediatric patients with rheumatic diseases is reassuring, but
      too limited to draw definite conclusions. More research is needed on the safety
      and efficacy of especially live-attenuated vaccines in patients with rheumatic
      and autoinflammatory diseases using high dose immunosuppressive drugs.

PMID- 21896343
TI  - On the trail to therapeutic antibodies.

PMID- 21896344
TI  - HIF-1alpha induction suppresses excessive lipid accumulation in alcoholic fatty
      liver in mice.
AB  - BACKGROUND & AIMS: Chronic alcohol intake stimulates hepatic oxygen consumption
      and subsequently causes liver hypoxia, leading to activation of hypoxia inducible
      factor-1 (HIF-1). Although HIF-1 plays a crucial role in the metabolic switch
      from aerobic to anaerobic metabolism in response to hypoxia, its roles in the
      regulation of lipid metabolism in alcoholic fatty liver remain unknown. METHODS:
      Wild-type and hepatocyte-specific HIF-1alpha-null mice were subjected to a 6%
      ethanol-containing liquid diet for 4 weeks, and functional effects of loss of the
      HIF-1alpha gene on lipid metabolism were examined in the liver. RESULTS:
      Hepatocyte-specific HIF-1alpha-null mice developed severe hypertriglyceridemia
      with enhanced accumulation of lipids in the liver of mice exposed to a 6% ethanol
      containing liquid diet for 4 weeks. Sterol regulatory element-binding protein 1c
      (SREBP-1c) and its downstream target acetyl-CoA carboxylase were greatly
      activated as the hepatic steatosis progressed, and these alterations were
      inversely correlated with the expression of the HIF-1-regulated gene DEC1.
      Overexpression of DEC1 in the mutant liver abrogated the detrimental effects of
      loss of HIF-1alpha gene on ethanol-induced fatty liver with reduced SREBP-1c
      expression. Conversely, co-administration of the HIF hydroxylase inhibitor
      dimethyloxalylglycine for the last 2 weeks improved markedly the ethanol-induced
      fatty liver in mice. CONCLUSIONS: The current results provide direct evidence for
      protective roles of HIF-1 induction in the development of ethanol-induced fatty
      liver via activation of the HIF-1-regulated transcriptional repressor DEC1.

PMID- 21896345
TI  - Reduced-intensity allogeneic stem cell transplantation in children and young
      adults with ultrahigh-risk pediatric sarcomas.
AB  - Some subsets of pediatric sarcoma patients have very poor survival rates. We
      sought to determine the feasibility and efficacy of allogeneic hematopoietic stem
      cell transplantation (alloHSCT) in pediatric sarcoma populations with <25%
      predicted overall survival (OS). Patients with ultrahigh-risk Ewing's sarcoma
      family of tumors (ESFT), alveolar rhabdomyosarcoma, or desmoplastic small round
      cell tumors received EPOCH-fludarabine induction, a
      cyclophosphamide/fludarabine/melphalan preparative regimen, and HLA matched
      related peripheral blood stem cells. Thirty patients enrolled; 7 did not undergo
      alloHSCT because of progressive disease with diminishing performance status
      during induction. All 23 alloHSCT recipients experienced rapid full-donor
      engraftment, with no peritransplantation mortality. Five of 23 alloHSCT
      recipients (22%) remain alive (OS of 30% by Kaplan-Meier analysis at 3 years),
      including 3 of 7 (42%) transplanted without overt disease (median survival 14.5
      versus 29.0 months from alloHSCT for patients transplanted with versus without
      overt disease, respectively). Among the 28 patients who progressed on the study,
      the median survival from date of progression was 1.9 months for the 7 who did not
      receive a transplant compared with 11.4 months for the 21 transplanted (P =
      .0003). We found prolonged survival after posttransplantation progression with
      several patients exhibiting indolent tumor growth. We also saw several patients
      with enhanced antitumor effects from posttransplantation chemotherapy (objective
      response to pretransplantation EPOCH-F was 24% versus 67% to posttransplantation
      EOCH); however, this was associated with increased toxicity. This largest
      reported series of alloHSCT in sarcomas demonstrates that alloHSCT is safe in
      this population, and that patients undergoing alloHSCT without overt disease show
      higher survival rates than reported using standard therapies. Enhanced chemo- and
      radiosensitivity of tumors and normal tissues was observed posttransplantation.

PMID- 21896347
TI  - Childhood pneumococcal disease in Latin America: preventable but still deadly.

PMID- 21896346
TI  - Polymorphisms in genes that regulate cyclosporine metabolism affect cyclosporine
      blood levels and clinical outcomes in patients who receive allogeneic
      hematopoietic stem cell transplantation.
AB  - In patients who received allogeneic hematopoietic stem cell transplantation
      (HSCT), we investigated the correlations between single nucleotide polymorphisms
      (SNPs) in genes that regulate cyclosporine metabolism and clinical outcomes. All
      patients received sibling-matched HSCT. DNA samples of patients and donors were
      analyzed for 4 SNPs: MDR1 +1236C>T (rs1128503), +2677G>T>A (rs2032582), +3435C>T
      (rs1045642), and CYP3A5 +6986G>A (rs776746). A total of 156 patients (median age
      40 years) were analyzed. Nineteen patients received HSCT for nonmalignant
      disease. The CYP3A5 +6986AA genotype was associated with a high cyclosporine
      blood level after transplantation. However, this genotype was not related to any
      particular clinical outcome. In contrast, the MDR1 +1236C>T SNP was correlated
      with specific clinical outcomes. When neither the donor nor the recipient had the
      CC genotype of MDR1 +1236, patients had lower creatinine levels (P < .001) and
      less transplantation-related mortality (TRM) (P = .012). These patients also
      showed longer overall survival (OS) in both univariate (P = .003) and
      multivariate (P = .003) analyses. Although the CYP3A5 +6986AA genotype was
      correlated with a high blood cyclosporine concentration, lack of the MDR1 +1236CC
      genotype in both the donor and recipient was correlated with less TRM and a
      longer OS in patients who received allogeneic HSCT.

PMID- 21896348
TI  - Prevention of pneumococcal disease through vaccination.
AB  - The Millennium Development Goals (MDGs), adopted by world leaders in the year
      2000 with an aim to accomplish them by 2015, provide concrete benchmarks for
      tackling extreme poverty in its many dimensions. One aim is to reduce by two
      thirds the mortality rate among children <5 years of age. The deaths of nearly 3
      million children under 5 each year worldwide can be attributed to diarrhea and
      pneumonia. Pneumonia, one form of pneumococcal disease, causes almost 1 in 5
      deaths of children under 5 worldwide-more than 1.6 million children each year.
      Pneumococcal disease is preventable by vaccination; because antibiotic resistance
      is a growing problem worldwide, there is a great need to promote effective
      pneumococcal vaccines. Vaccines differ from other types of drugs, because they
      are administered to healthy individuals. Therefore, a good safety profile is
      required, there is a large governmental regulatory role, and low efficacy is
      unacceptable. Other important considerations are as follows: vaccines are often
      used in infants, are typically given in multiple doses, the manufacturing is a
      larger part of cost, requires high regulatory and quality control burden and
      minimization of costs. From a biological standpoint, the induction of vaccine
      mediated protection is a complex procedure. Long-term protection typically
      requires the persistence of anti-microbial antibodies and/or the generation of
      immune memory cells capable of rapid and effective reactivation after microbial
      re-exposure. Appreciation of the predominant role of B cells in the efficacy of
      current vaccines should not minimize the importance of generating a T cell
      response, as this is essential for the induction of high affinity antibodies and
      immune memory. Pneumococcal capsular polysaccharides typically elicit B cell
      responses in a T-independent manner. Because of this, capsular polysaccharides
      are poorly immunogenic in children below 2 years of age and will generate an IgM
      isotype-based primary response with only short-lived protection. The conjugation
      of capsular polysaccharides to a protein carrier provides an antigenic complex in
      a form that can be presented to the immune system and thus recruit antigen
      specific CD4+ cells (T-dependent antibody). Pneumococcal conjugate vaccines
      (PCVs), comprising pneumococcal polysaccharides conjugated to a protein carrier,
      not only induce antibodies but also prime the immune system for protective memory
      response. These vaccines provide protection in children below 2 years of age,
      generate long-term protection (highly specific IgG antibodies), generate herd
      immunity (indirect protection of nonimmunized individuals) and have demonstrated
      effectiveness in regions that have incorporated them into the national
      immunization schedules. Global implementation of PCVs has contributed to
      substantial progress toward reducing childhood mortality, but increased vaccine
      uptake in developing regions such as Latin America and the Caribbean is necessary
      to continue toward accomplishing the goals outline in the MDGs.

PMID- 21896349
TI  - Pneumococcal disease manifestation in children before and after vaccination:
      what's new?
AB  - Pneumococcal infections remain a relevant cause of morbidity and mortality in
      children, especially in countries where vaccination has not been introduced. In
      contrast to the common belief by many pediatricians, the most important
      pneumococcal infections are of the respiratory tract and not invasive diseases.
      The recent pandemic of the H1N1 virus prompted studies to better understand the
      interaction between the influenza virus, Streptococcus pneumoniae, and pneumonia
      outcomes. Radiological findings of bacteremic pneumonia have been well
      investigated and besides the typical alveolar consolidation, a broad spectrum of
      atypical patterns has been reported. Molecular techniques, such as real-time
      polymerase chain reaction (PCR), can improve the detection of S. pneumoniae in
      sterile fluids, mainly in regions where previous antibiotic therapy is a common
      practice. In the post vaccination era, new manifestations of pneumococcal
      invasive disease, such as hemolytic uremic syndrome, have increased in
      association with parapneumonic empyema. Moreover, serotypes not included in PCV7,
      particularly serotypes 1, 3, 5, 7F, and 19A, have been among the most common
      isolates in pneumococcal disease. In Latin America, pneumococcal primary
      peritonitis has been described as an important clinical syndrome in a growing
      proportion of patients, mainly in girls. The development of newer and more
      specific diagnostic markers to distinguish bacterial and viral pneumonia are
      urgently sought, and will be especially pertinent after the introduction of
      pneumococcal conjugate vaccines with expanded serotypes. Such markers would
      minimize inappropriate diagnosis of false positive cases and treatment with
      antibacterial agents, while increasing positive predictive values for diagnosis
      of bacterial pneumonia. The extension of serotype coverage with the new conjugate
      vaccines is promising for pneumococcal infections and coverage against antibiotic
      resistant strains.

PMID- 21896350
TI  - Prevenar experience.
AB  - Streptococcus pneumoniae is one of the leading bacterial pathogens causing
      invasive disease and non-invasive infections at both extremes of life: in
      children younger than 5 years and in elderly persons of 65 years or more.
      Pneumococcal infections result in substantial morbidity and mortality among
      children under 5 years of age; it is estimated that 1,600,000 deaths occur per
      year in that age range alone, mostly in developing countries, thus representing a
      serious public health problem around the globe. Infections caused by S.
      pneumoniae are considered by the World Health Organization (WHO) as the number
      one vaccine-preventable cause of death in children younger than 5 years of age.
      In 2000, the first heptavalent conjugated pneumococcal vaccine (PCV7) was
      licensed in the United States, differing from the already available non
      conjugated polysaccharide pneumococcal vaccine in its ability to induce a
      protective immune response in children under 2 years of age. Initial efficacy
      studies in the United States with PCV7 revealed a 97.4% efficacy against invasive
      pneumococcal disease (IPD) caused by vaccine serotypes (4, 9V, 14, 19F, 23F, 18C
      and 6B). PCV7 was introduced into the National Immunization Program (NIP) of
      various countries starting in year 2000 and, after 11 years of use, the data
      confirm that PCV7 introduction resulted in a major reduction of S. pneumoniae
      IPD, non-bacteremic pneumonia, otitis media medical visits, the need for tympanic
      tubes, the number of cases of otorrhea and of various antimicrobial resistant
      strains in children <5 years of age. Additionally, reductions in S. pneumoniae
      infections have been observed in unvaccinated children above 5 years of age and
      adults including individuals older than 65 years of age (herd effect).
      Effectiveness has been observed in countries using a 4-dose regimen (3 infant
      doses followed by a booster during the second year of life) but also in countries
      with modified reduced doses (2 infant doses and a booster during the second year
      of life or after 3 infant doses with no booster).

PMID- 21896351
TI  - The pharmacoeconomics of pneumococcal conjugate vaccines in Latin America.
AB  - Streptococcus pneumoniae continues to be the most important causative agent of
      invasive bacterial infections in children and is the most common cause of vaccine
      preventable deaths in children less than 5 years of age. Due to some conditions
      in the Latin America region, economic assessments of pneumococcal conjugate
      vaccines (PCVs) have unique characteristics. First, distribution of S. pneumoniae
      serotypes, and thus coverage by vaccines that incorporate certain serotypes,
      varies within the region and compared with other parts of the world. Second, the
      mortality rate of pneumococcal infections in developing countries is
      significantly higher than in the US and Europe. Third, the economies of the Latin
      American region are very different from those of developed countries. For these
      reasons, the Pan American Health Organization (PAHO) is promoting the need for
      economic valuation studies of the impact of pneumococcal vaccines Latin America.
      Given the importance of pneumonia in the burden of pneumococcal disease in Latin
      America, the number of pneumonia cases prevented by the vaccine has a large
      impact on the economic valuation of PCVs, due to a strong correlation with
      numbers of deaths averted, quality-adjusted life-years (QALYs) gained or
      disability-adjusted life-years (DALYs) avoided. In terms of cost, analysis of
      impact on acute otitis media (short-term) and sequelae (long-term) show a
      significant and important expenditure avoided by vaccination. Cost-effectiveness
      is significantly modified by vaccine cost, mortality due to pneumonia, vaccine
      efficacy/effectiveness and herd immunity. Finally the validity of certain
      assumptions based on the uncertainty of the data should be considered in economic
      assessments of new PCVs. These include assumptions related to the impact on
      otitis media, estimates of efficacy/effectiveness based on measured antibody
      levels and the extrapolation to PCV10 and PCV13 of previous experience with PCV7.

PMID- 21896352
TI  - The future of pneumococcal disease prevention.
AB  - Pneumococcal disease (PD) is the leading cause of vaccine preventable deaths in
      children <5 years of age worldwide, with most of the deaths occurring in the
      developing world. Prevention of PD in children has been achieved by vaccination
      with pneumococcal conjugate vaccine (PCV), the basis for which is induction of a
      protective antibody response against the bacterial polysaccharide capsule.
      Conjugation of the polysaccharide capsule to a protein carrier enables the
      generation of an immunologic response to the vaccine in young children, leading
      to protection against infection. The heptavalent PCV, which contains 7 of the 93
      known pneumococcal serotypes (4, 6B, 9V, 14, 18C, 19F, 23F) was the first PCV
      available, licensed in the US in 2000 and subsequently in many countries
      worldwide, including Latin American and Caribbean countries. Since its
      introduction, PCV7 has been documented effective for reducing invasive PD
      mortality and burden, as well as that of pneumonia and otitis media.
      Additionally, PD caused by the vaccine serotypes has decreased in the unimmunized
      population due to herd immunity induced by PCV7. Despite this success,
      significant disease burden still exists globally due to serotypes not included in
      PCV7. Currently there are 2 new PCVs that have been approved for use in children,
      a 10-valent vaccine (includes PCV7 serotypes plus serotypes 1, 5 and 7F) and a 13
      valent vaccine (includes PCV7 serotypes plus serotypes 1, 3, 5, 6A, 7F and 19A).
      The selection of new serotypes to be included was based on importance of these
      serotypes as causes of PD. An additional 15-valent vaccine (includes PCV 7
      serotypes plus serotypes 1, 3, 5, 6A, 7F, 19A, 22F and 33F) is undergoing
      clinical trial testing. In view of the 93 serotypes that are currently known, it
      seems clear that vaccines with greater coverage, likely based on proteins common
      to all serotypes, will be needed in the future. Technical and regulatory
      challenges to the development and approval of newer PCVs include a need for
      licensing criteria of common protein vaccines, establishment of correlates of
      protection for disease manifestations other than invasive disease, comparative
      efficacy data, and clinical trial testing of concomitant immunization of higher
      valency PCVs with other vaccines.

PMID- 21896353
TI  - Global health, global health education, and infectious disease: the new
      millennium, Part II.

PMID- 21896354
TI  - Editorial: Transforming global health, global health education, infectious
      disease, and chronic conditions in the 21st century.
AB  - Chronic and infectious diseases, including health care-associated infections and
      tropical diseases, represent a large portion of the global health burden.
      Solutions need to be found while addressing other health priorities identified by
      the Millennium Development Goals. A number of organizations and initiatives have
      been created to meet this need. Developing countries in Latin America and several
      African countries are taking a larger role in the development of robust health
      systems, capacity building, and education. Integrated, efficient, and equitable
      health systems that incorporate primary, secondary, and tertiary care models with
      a research focus are critically needed to fill this void.

PMID- 21896355
TI  - The University of California Global Health Institute opportunities and
      challenges.
AB  - The creation of the University of California Global Health Institute represents a
      paradigm shift in structure and function. Its 3 centers of expertise (Migration
      and Health, One Health, and Women's Health and Empowerment) not only involve all
      10 of the University of California campuses but also bring together a wide range
      of disciplines from both the health and nonhealth sciences. They have created
      truly interdisciplinary and transdisciplinary programs that are addressing
      complex global health challenges of the twenty-first century, training future
      global health leaders, and forging international academic partnerships.

PMID- 21896356
TI  - Global health: the Fogarty International Center, National Institutes of Health:
      vision and mission, programs, and accomplishments.
AB  - The Fogarty International Center (FIC) of the US National Institutes of Health
      has supported long-term training and research for more than 3600 future leaders
      in science and public health from low-income and middle-income countries; tens of
      thousands more persons have received short-term training. More than 23 extramural
      training and research programs plus an intramural program are now operating.
      Newer FIC training programs are addressing chronic, noncommunicable diseases and
      strengthening the quality of medical schools and health care provider training.
      Most FIC trainees return to their countries of origin, where they mentor and
      train thousands of individuals in their home countries.

PMID- 21896357
TI  - The Asia Pacific Academic Consortium for Global Public Health and medicine:
      stabilizing south-south academic collaboration.
AB  - Developmental strategies over the last 4 decades have generally tended to
      transfer knowledge and technology along north-south axes as trickle-down theories
      in development, especially in health knowledge transfers, prevailed. Limited
      efforts in development assistance for health (DAH) were made to promote south
      south cooperation for basic health needs. Globalization with increased
      educational networks and development health assistance has enhanced the potential
      for more effective south-south partnerships for health. The stages of development
      in a consortium and key catalysts in the metamorphosis to a south-south
      partnership are identified: leadership, resources, expertise, visibility
      participation, and dynamism of a critical mass of young professionals.

PMID- 21896358
TI  - Global health in the UK government and university sector.
AB  - In this article, the authors review recent global health activities in the United
      Kingdom by key organisations in several defined areas:- UK government
      (international aid and global health strategy); UK research funding agencies
      (overseas research units); non-governmental organisations; UK universities and
      hospitals and academic/clinical international partnerships;professional
      societies; UK undergraduate and postgraduate training opportunities in global
      health; and opportunities for international medical graduates.

PMID- 21896359
TI  - Competencies for global heath graduate education.
AB  - Competency specification and competency-based education (CBE) are increasingly
      being viewed as essential for optimizing educational outcomes for the next
      generation of global health workers. An overview is provided of this movement in
      graduate health professions education in the United States, the Association of
      Schools of Public Health (ASPH) contributions to advancing and researching
      related CBE processes and best practices, and the evolving ASPH competency model
      for graduate global health education.

PMID- 21896360
TI  - Globalization and infectious diseases.
AB  - This article discusses the nature of the health challenges created by
      globalization and proposes new forms of international cooperation to confront
      them. The discussion of global health challenges includes both the transfer of
      health risks, with an emphasis on infectious diseases, and the international
      dissemination of health opportunities, including the transfer of knowledge and
      technology. The authors argue that the health-related challenges and
      opportunities of an increasingly interdependent world demand new forms of
      international cooperation. The authors suggest the promotion of 3 elements that,
      in their essence, contain the idea of collaboration: exchange, evidence, and
      empathy.

PMID- 21896361
TI  - Global health diplomacy and peace.
AB  - Diplomacy and health are in a period of rapid transition, so this article
      elaborates on the complex multilevel, multiactor negotiation processes that shape
      and manage the global policy environment for health. It explores the dynamic
      relationship between health and foreign policy and provides examples from the
      national, regional, and global levels. Reflecting on the deliberations in
      different international bodies, it discusses key questions and opportunities that
      could contribute to moving forward both health and peace agendas. The concluding
      remarks draw attention to the importance of bridging the capacity gap.

PMID- 21896363
TI  - Global health: chronic diseases and other emergent issues in global health.
AB  - Infectious diseases have had a decisive and rapid impact on shaping and changing
      health policy. Noncommunicable diseases, while not garnering as much interest or
      importance over the past 20 years, have been affecting public health around the
      world in a steady and critical way, becoming the leading cause of death in
      developed and developing countries. This article discusses emergent issues in
      global health related to noncommunicable diseases and conditions, with focus on
      defining the unique epidemiologic features and relevant programmatic, health
      systems, and policy responses concerning noncommunicable chronic diseases, mental
      health, accidents and injuries, urbanization, climate change, and disaster
      preparedness.

PMID- 21896362
TI  - Poverty, global health, and infectious disease: lessons from Haiti and Rwanda.
AB  - Poverty and infectious diseases interact in complex ways. Casting destitution as
      intractable, or epidemics that afflict the poor as accidental, erroneously
      exonerates us from responsibility for caring for those most in need. Adequately
      addressing communicable diseases requires a biosocial appreciation of the
      structural forces that shape disease patterns. Most health interventions in
      resource-poor settings could garner support based on cost/benefit ratios with
      appropriately lengthy time horizons to capture the return on health investments
      and an adequate accounting of externalities; however, such a calculus masks the
      suffering of inaction and risks eroding the most powerful incentive to act:
      redressing inequality.

PMID- 21896364
TI  - Global health: neglected diseases and access to medicines.
AB  - The World Health Organization has developed a comprehensive plan to deal with
      neglected tropical diseases (NTDs). Compared with a decade ago, more resources
      are being spent to address the problem of neglected diseases, and considerable
      progress has been made. However, NTDs remain neglected, deepening the global
      inequities in health. The current efforts do not implement a multiprong strategy
      and are effective in the short term, but do not generate long-term, sustainable
      solutions. This article discusses the current successes in providing access to
      medicine for treatment of a multitude of neglected diseases, and the
      opportunities to achieve global equality in health.

PMID- 21896365
TI  - Global health: injuries and violence.
AB  - Injury and violence rank among the leading causes of death worldwide, with more
      than 5 million deaths annually, representing a significant portion of the global
      burden of disease. This article examines how injury and violence relate to global
      health using recent global burden of disease data and selected key studies and
      databases, and further explores risk factors and intervention initiatives that
      address unintentional and intentional injuries. The article serves as a call to
      action to enhance understanding of the growing burden of injury and violence,
      especially in low-income and middle-income countries, where more than 90% of
      injuries occur.

PMID- 21896366
TI  - Basic science research and education: a priority for training and capacity
      building in developing countries.
AB  - This article provides evidence that basic science research and education should
      be key priorities for global health training, capacity building, and practice.
      Currently, there are tremendous gaps between strong science education and
      research in developed countries (the North) as compared to developing countries
      (the South). In addition, science research and education appear as low priorities
      in many developing countries. The need to stress basic science research beyond
      the typical investment of infectious disease basic service and research
      laboratories in developing areas is significant in terms of the benefits, not
      only to education, but also for economic strengthening and development of human
      resources. There are some indications that appreciation of basic science research
      education and training is increasing, but this still needs to be applied more
      rigorously and strengthened systematically in developing countries.

PMID- 21896367
TI  - Global laboratory systems development: needs and approaches.
AB  - Functional laboratory systems are a key component of country health care systems.
      Laboratory strengthening in resource-limited countries has been supported by
      disease-specific vertical programs that have focused on laboratory methods,
      procedures, and supplies for a country program, and providing training in
      performing tests. A health systems focus requires attention to regulations,
      management of national systems, national approaches to quality assurance, and
      education of laboratory scientists. An immediate focus of resources on the
      components required for a functioning system and continued technical support will
      enable countries to assume responsibility for their country-specific needs and
      improve their capability to address international responsibilities.

PMID- 21896368
TI  - Drugs and diagnostic innovations to improve global health.
AB  - Infectious diseases remain the major cause of morbidity and mortality in the
      developing world. Affordable effective drugs and diagnostics are critical for
      patient management and disease control but the development of new drugs and
      diagnostics is too slow to keep up with the emergence and spread of infectious
      diseases around the world. Innovative collaborative research and development
      involving disease endemic countries and developed countries are urgently needed
      to accelerate progress along the path from discovery to product adoption. These
      emerging approaches and the need for increased investment in human and financial
      resources to support them are discussed.

PMID- 21896369
TI  - The size and burden of mental disorders and other disorders of the brain in
      Europe 2010.
AB  - AIMS: To provide 12-month prevalence and disability burden estimates of a broad
      range of mental and neurological disorders in the European Union (EU) and to
      compare these findings to previous estimates. Referring to our previous 2005
      review, improved up-to-date data for the enlarged EU on a broader range of
      disorders than previously covered are needed for basic, clinical and public
      health research and policy decisions and to inform about the estimated number of
      persons affected in the EU. METHOD: Stepwise multi-method approach, consisting of
      systematic literature reviews, reanalyses of existing data sets, national surveys
      and expert consultations. Studies and data from all member states of the European
      Union (EU-27) plus Switzerland, Iceland and Norway were included. Supplementary
      information about neurological disorders is provided, although methodological
      constraints prohibited the derivation of overall prevalence estimates for mental
      and neurological disorders. Disease burden was measured by disability adjusted
      life years (DALY). RESULTS: Prevalence: It is estimated that each year 38.2% of
      the EU population suffers from a mental disorder. Adjusted for age and
      comorbidity, this corresponds to 164.8million persons affected. Compared to 2005
      (27.4%) this higher estimate is entirely due to the inclusion of 14 new disorders
      also covering childhood/adolescence as well as the elderly. The estimated higher
      number of persons affected (2011: 165m vs. 2005: 82m) is due to coverage of
      childhood and old age populations, new disorders and of new EU membership states.
      The most frequent disorders are anxiety disorders (14.0%), insomnia (7.0%), major
      depression (6.9%), somatoform (6.3%), alcohol and drug dependence (>4%), ADHD
      (5%) in the young, and dementia (1-30%, depending on age). Except for substance
      use disorders and mental retardation, there were no substantial cultural or
      country variations. Although many sources, including national health insurance
      programs, reveal increases in sick leave, early retirement and treatment rates
      due to mental disorders, rates in the community have not increased with a few
      exceptions (i.e. dementia). There were also no consistent indications of
      improvements with regard to low treatment rates, delayed treatment provision and
      grossly inadequate treatment. Disability: Disorders of the brain and mental
      disorders in particular, contribute 26.6% of the total all cause burden, thus a
      greater proportion as compared to other regions of the world. The rank order of
      the most disabling diseases differs markedly by gender and age group; overall,
      the four most disabling single conditions were: depression, dementias, alcohol
      use disorders and stroke. CONCLUSION: In every year over a third of the total EU
      population suffers from mental disorders. The true size of "disorders of the
      brain" including neurological disorders is even considerably larger. Disorders of
      the brain are the largest contributor to the all cause morbidity burden as
      measured by DALY in the EU. No indications for increasing overall rates of mental
      disorders were found nor of improved care and treatment since 2005; less than one
      third of all cases receive any treatment, suggesting a considerable level of
      unmet needs. We conclude that the true size and burden of disorders of the brain
      in the EU was significantly underestimated in the past. Concerted priority action
      is needed at all levels, including substantially increased funding for basic,
      clinical and public health research in order to identify better strategies for
      improved prevention and treatment for disorders of the brain as the core health
      challenge of the 21st century.

PMID- 21896370
TI  - Pediatric-to-adult nephrology: the handoff.

PMID- 21896371
TI  - Gamut of CKD across the age divide.

PMID- 21896372
TI  - Genetics and CKD.
AB  - The diagnosis of hereditary monogenic kidney diseases is frequently delayed, in
      part because of physicians' unfamiliarity with the relatively rare conditions or
      because of the late onset of symptoms in some patients. Molecular biology methods
      have clarified the underlying mutations in several types of CKD, and in the
      process have revealed previously unknown genes and pathogenetic pathways.
      Mutations affecting the integrity of the glomerular filtration barrier cause
      proteinuria or nephrotic syndrome; different types of Alport syndrome are caused
      by mutations in glomerular basement membrane type IV collagen; dysfunction of the
      primary cilium of tubule cells may lead to a variety of inherited progressive
      tubulointerstitial diseases; atypical hemolytic-uremic syndrome is frequently
      caused by inherited complement deficiencies; and progressive kidney injury
      develops in many inherited systemic or metabolic disorders. Some genetic diseases
      may not manifest until late childhood or adulthood. Accurate diagnosis is
      important for appropriate treatment, prognosis, genetic counseling, and possible
      renal transplantation.

PMID- 21896373
TI  - Growth in chronic kidney disease.
AB  - Poor growth is a common sequela of CKD in childhood. It not only affects the
      psychosocial development of a child but also has significant effects even in the
      adult life. The multifactorial etiology and severe consequences of growth failure
      in CKD warrant evaluation of all the modifiable and nonmodifiable causes.
      Treatment strategies must be directed toward the specific factors for each child
      with CKD. Among the various metabolic, nutritional, and hormonal disturbances
      complicating CKD, disordered growth hormone (GH) and insulin-like growth factor-1
      axis are important contributors toward poor growth in children with CKD. CKD is
      recognized as a state of GH resistance rather than GH deficiency, with multiple
      mechanisms contributing to this GH resistance. Recombinant GH (rGH) therapy can
      be used in this population to accelerate growth velocity. Although its use has
      been shown to be effective and safe in children with CKD, there continues to be
      some uncertainty and reluctance among practitioners and families regarding its
      usage, thereby resulting in a surprisingly low use in children with CKD. This
      review focuses on the pathogenesis of growth failure, its effect, and management
      strategies in children with CKD.

PMID- 21896374
TI  - Focal segmental glomerulosclerosis and chronic kidney disease in pediatric
      patients.
AB  - Focal segmental glomerulosclerosis (FSGS) is one of the most common forms of
      acquired glomerular disease leading to end-stage kidney disease. Its incidence is
      rising around the world. There is no proven therapy for those patients who do not
      respond to corticosteroids and it can recur in 20% to 25% of patients who receive
      a kidney transplant. The disease can be primary, or it can be secondary to
      various conditions including vesicoureteral reflux, obesity, medications, and
      infections. Recent advances have demonstrated the important role of genetic
      mutations in podocyte proteins as a cause of FSGS. There is an urgent need for
      randomized clinical trials to develop safe and effective therapy for FSGS that
      occurs in the native or transplanted kidney.

PMID- 21896375
TI  - The spectrum of polycystic kidney disease in children.
AB  - Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive
      polycystic kidney disease (ARPKD) are important inherited kidney diseases with
      distinct clinical features and genetics. Although these diseases have classically
      been considered "adult" (ADPKD) or "infantile/pediatric" (ARPKD), it is now clear
      that both diseases can present in children and adults. ADPKD and ARPKD also share
      important pathophysiologic features, including cilia dysfunction. ADPKD is a
      systemic disease involving cysts in the kidneys and abdominal organs as well as
      abnormalities in the heart and vasculature. Although it typically presents in
      adults, ADPKD has been diagnosed in fetuses, infants, children, and adolescents.
      The majority of children diagnosed with ADPKD are asymptomatic. Those with
      symptoms typically present with hypertension or gross hematuria. Routine
      screening for renal cysts in asymptomatic children who have a parent with ADPKD
      is generally not recommended. ARPKD is a disorder confined to the kidneys
      (polycystic kidneys) and liver (a developmental biliary lesion called congenital
      hepatic fibrosis). Although most children with ARPKD present in infancy with
      large, echogenic kidneys, a subset present later in childhood and even adulthood,
      primarily with complications related to the liver disease. As more patients with
      ARPKD survive to adulthood, these liver complications are likely to become more
      prevalent.

PMID- 21896377
TI  - Hypertension and CKD.
AB  - Hypertension is found in more than 50% of pediatric patients with CKD. However,
      its prevalence varies according to the cause of CKD. It is relatively infrequent
      in children with structural disorders. Acquired renal disorders are associated
      with an increased prevalence of hypertension, similar to that of adults. Recent
      studies using ambulatory blood pressure monitoring indicate that children with
      CKD also have a high prevalence of masked hypertension. Similar to adults, long
      standing and uncontrolled hypertension in children is associated with the
      progression of CKD and development of end-organ damage including early
      cardiomyopathy and premature atherosclerosis. Aggressive treatment of
      hypertension should be an essential part of pediatric CKD care, not just to
      prevent the development of symptomatic cardiovascular disease but also to delay
      progression of CKD. Recent findings from the European Effect of Strict Blood
      Pressure Control and ACE Inhibition on Progression of Chronic Renal Failure in
      Pediatric Patients (ESCAPE) trial have shown that the aggressive treatment of
      blood pressure, to below the 50th percentile, has even greater benefit in
      children with CKD, unlike results seen in adult studies.

PMID- 21896376
TI  - Vesicoureteral reflux and reflux nephropathy.
AB  - Primary vesicoureteral reflux (VUR) is the commonest congenital urological
      abnormality in children, which has been associated with an increased risk of
      urinary tract infection (UTI) and renal scarring, also called reflux nephropathy
      (RN). In children, RN is diagnosed mostly after UTI (acquired RN) or during
      follow-up for antenatally diagnosed hydronephrosis with no prior UTI (congenital
      RN). The acquired RN is more common in female children, whereas the congenital RN
      is more common in male children. This observation in children might help explain
      the differences in the clinical presentation of RN in adults, with males
      presenting mostly with hypertension, proteinuria, and progressive renal failure
      as compared with females who present mostly with recurrent UTI and have a better
      outcome. Known risk factors for RN include the severity of VUR, recurrent UTI,
      and bladder-bowel dysfunction; younger age and delay in treatment of UTI are
      believed to be other risk factors. Management of VUR is controversial and
      includes antimicrobial prophylaxis, surgical intervention, or surveillance only.
      No evidence-based guidelines exist for appropriate follow-up of patients with RN.

PMID- 21896378
TI  - CKD and bladder problems in children.
AB  - Approximately 35% of children with CKD who require renal replacement therapy have
      a significant urological abnormality, including posterior urethral valves, a
      neuropathic bladder, prune belly syndrome, Hinman syndrome, or severe
      vesicoureteral reflux. In such children, abnormal bladder function can have a
      significant deleterious effect on the renal function. In children with bladder
      outlet obstruction, bladder compliance and capacity often are abnormal, and a
      sustained intravesical pressure of >40 cm H(2)O impedes drainage from the upper
      urinary tract. Consequently, in these conditions, regular evaluation with renal
      sonography, urodynamics, urine culture, and serum chemistry needs to be
      performed. Pediatric urological care needs to be coordinated with pediatric
      nephrologists. Many boys with posterior urethral valves have severe polyuria,
      resulting in chronic bladder overdistension, which is termed as valve bladder. In
      addition to behavioral modification during the day, such patients may benefit
      from overnight continuous bladder drainage, which has been shown to reduce
      hydronephrosis and stabilize or improve renal function in most cases. In children
      with a neuropathic bladder, detrusor-sphincter-dyssynergia is the most likely
      cause for upper tract deterioration due to secondary vesicoureteral reflux,
      hydronephrosis, and recurrent urinary tract infection (UTI). Pharmacologic
      bladder management and frequent intermittent catheterization are necessary. In
      some cases, augmentation cystoplasty is recommended; however, this procedure has
      many long-term risks, including UTI, metabolic acidosis, bladder calculi,
      spontaneous perforation, and malignancy. Nearly half of children with prune belly
      syndrome require renal replacement therapy. Hinman syndrome is a rare condition
      with severe detrusor-sphincter discoordination that results in urinary
      incontinence, encopresis, poor bladder emptying, and UTI, often resulting in
      renal impairment. Children undergoing evaluation for renal transplantation need a
      thorough evaluation of the lower urinary tract, mostly including a voiding
      cystourethrogram and urodynamic studies.

PMID- 21896379
TI  - Nephrolithiasis in children.
AB  - Similar to adults, stone disease in the pediatric patient may present clinically
      as flank/abdominal pain or hematuria. Unlike in adults, pediatric stone disease
      is less frequent and is often associated with an underlying metabolic disorder.
      Because of the 50% likelihood of finding an underlying metabolic cause for stone
      formation in younger children, a metabolic workup is recommended for all children
      with stone disease, including first-time stone formers. Stone analysis, when
      available, can be very helpful in determining an underlying cause. If needed, all
      modalities of minimally invasive surgical treatment are possible for children
      with stones. Surgical approaches may be needed to achieve the goal of nephron
      preservation. Aggressive fluid intake is the mainstay of prevention for all forms
      of stone disease, but specific therapy targeted to the most likely underlying
      metabolic abnormality is often used. Newer data are now linking stone disease to
      CKD, thereby emphasizing the need for a better understanding and potentially more
      aggressive treatment approach. With increasing frequency of stone disease in the
      pediatric patient and increasing survival of these patients into adulthood, the
      adult caregiver must become familiar with different causes and treatment
      approaches to stone disease in young adult patients in whom disease onset began
      in childhood.

PMID- 21896380
TI  - Advances in pediatric renal replacement therapy.
AB  - Advances in the understanding and clinical application of hemodialysis,
      peritoneal dialysis, and continuous renal replacement therapy have resulted in
      strategies designed to further improve their safety and efficacy. These advances
      have been particularly important to children, in whom a variety of clinical and
      technical issues must be taken into consideration for optimum dialysis across a
      broad spectrum of patient size and need. This manuscript reviews recent data
      pertaining to the use of renal replacement therapy, with an emphasis on those
      aspects of dialysis management that are especially pertinent to pediatric ESRD
      and acute kidney injury care.

PMID- 21896381
TI  - Health care transition for adolescents with CKD-the journey from pediatric to
      adult care.
AB  - The design of Health Care Transition (HCT) services for adolescents and emerging
      adults with CKD or end-stage kidney disease (ESKD) needs to take into account
      patient cognition/developmental stage, family factors, and health resources
      within the hospital setting and community. Patient and family education is
      fundamental and teaching and learning tools must be literacy-accessible.
      Adolescents and emerging adults with CKD/ESDK have complex medical and dietary
      regimes, and therapeutic adherence is important for optimizing their health,
      quality of life, and longevity. Health providers need to identify ways of
      engaging them to become successful disease self-mangers. Interdisciplinary
      collaboration between the pediatric- and adult-focused health care teams and the
      services of a dedicated transition coordinator are paramount to ensure clear
      communication between the patient and the health professionals involved. Valid
      measurement tools to monitor and assess the HCT process and health outcomes need
      to be developed. The aims of planned HCT for adolescents and/or emerging adults
      with CKD/ESKD are anchored by the goals of optimizing health outcomes, health
      related quality of life, and continuous quality improvement. The care of young
      people with CKD/ESKD can be both challenging and rewarding; we offer strategies
      for planned HCT services geared to these vulnerable patients.

PMID- 21896382
TI  - Building an index of activity of inhabitants from their activity on the
      residential electrical power line.
AB  - In the framework of context awareness within the home, our team is currently
      assessing the unobtrusive detection of inhabitants' activity through the
      monitoring of their use and consumption of electricity. The objective is to
      develop a system for the remote monitoring of large populations of elderly people
      living independently at home. To be readily deployable on the field, such a
      system must be minimally intrusive both for the home environment and for the
      field professionals (paramedics and social workers) visiting the patients at
      home. We carried out two successive field experiments to evaluate and to improve
      our system designed to deliver a single index of daily activity. The first
      experiment involved 13 elderly persons over a nine-month period (84,240 h data
      recorded) and the second one 12 elderly over six months (51,840 h). We evaluated
      both the relevance of the index and the acceptability of the system as a whole.
      We discovered that electrical activity is a kind of unique "signature" of each
      person's activity. Moreover, this profile provides unexpected information on the
      health status of the subject. We confirmed that the system was unobtrusive and
      well accepted both by the subjects and by the professionals involved. Our unique
      index of activity, and its trend over time, can provide timely information to the
      professionals on the patient.

PMID- 21896384
TI  - Construction of a computational anatomical model of the peripheral cardiac
      conduction system.
AB  - A methodology is presented here for automatic construction of a ventricular model
      of the cardiac conduction system (CCS), which is currently a missing block in
      many multiscale cardiac electromechanic models. It includes the His bundle, left
      bundle branches, and the peripheral CCS. The algorithm is fundamentally an
      enhancement of a rule-based method known as the Lindenmayer systems (L-systems).
      The generative procedure has been divided into three consecutive independent
      stages, which subsequently build the CCS from proximal to distal sections. Each
      stage is governed by a set of user parameters together with anatomical and
      physiological constrains to direct the generation process and adhere to the
      structural observations derived from histology studies. Several parameters are
      defined using statistical distributions to introduce stochastic variability in
      the models. The CCS built with this approach can generate electrical activation
      sequences with physiological characteristics.

PMID- 21896383
TI  - Effect of insertion speed on tissue response and insertion mechanics of a
      chronically implanted silicon-based neural probe.
AB  - In this study, the effect of insertion speed on long-term tissue response and
      insertion mechanics was investigated. A dummy silicon parylene-coated probe was
      used in this context and implanted in the rat brain at 10 MUm/s (n = 6) or 100
      MUm/s (n = 6) to a depth of 9 mm. The insertion mechanics were assessed by the
      dimpling distance, and the force at the point of penetration, at the end of the
      insertion phase, and after a 3-min rest period in the brain. After 6 weeks, the
      tissue response was evaluated by estimating the amount of gliosis, inflammation,
      and neuronal cell loss with immunohistochemistry. No difference in dimpling,
      penetration force, or the force after a 3-min rest period in the brain was
      observed. However, the force at the end of the insertion phase was significantly
      higher when inserting the probes at 100 MUm/s compared to 10 MUm/s. Furthermore,
      an expected tissue response was seen with an increase of glial and microglial
      reactivity around the probe. This reaction was similar along the entire length of
      the probe. However, evidence for a neuronal kill zone was observed only in the
      most superficial part of the implant. In this region, the lesion size was also
      greatest. Comparison of the tissue response between insertion speeds showed no
      differences.

PMID- 21896385
TI  - Enhanced patterns of oriented edge magnitudes for face recognition and image
      matching.
AB  - A good feature descriptor is desired to be discriminative, robust, and
      computationally inexpensive in both terms of time and storage requirement. In the
      domain of face recognition, these properties allow the system to quickly deliver
      high recognition results to the end user. Motivated by the recent feature
      descriptor called Patterns of Oriented Edge Magnitudes (POEM), which balances the
      three concerns, this paper aims at enhancing its performance with respect to all
      these criteria. To this end, we first optimize the parameters of POEM and then
      apply the whitened principal-component-analysis dimensionality reduction
      technique to get a more compact, robust, and discriminative descriptor. For face
      recognition, the efficiency of our algorithm is proved by strong results obtained
      on both constrained (Face Recognition Technology, FERET) and unconstrained
      (Labeled Faces in the Wild, LFW) data sets in addition with the low complexity.
      Impressively, our algorithm is about 30 times faster than those based on Gabor
      filters. Furthermore, by proposing an additional technique that makes our
      descriptor robust to rotation, we validate its efficiency for the task of image
      matching.

PMID- 21896386
TI  - A surface-based 3-D dendritic spine detection approach from confocal microscopy
      images.
AB  - Determining the relationship between the dendritic spine morphology and its
      functional properties is a fundamental challenge in neurobiology research. In
      particular, how to accurately and automatically analyse meaningful structural
      information from a large microscopy image data set is far away from being
      resolved. As pointed out in existing literature, one remaining challenge in spine
      detection and segmentation is how to automatically separate touching spines. In
      this paper, based on various global and local geometric features of the dendrite
      structure, we propose a novel approach to detect and segment neuronal spines, in
      particular, a breaking-down and stitching-up algorithm to accurately separate
      touching spines. Extensive performance comparisons show that our approach is more
      accurate and robust than two state-of-the-art spine detection and segmentation
      algorithms.

PMID- 21896387
TI  - Text-line extraction in handwritten Chinese documents based on an energy
      minimization framework.
AB  - Text-line extraction in unconstrained handwritten documents remains a challenging
      problem due to nonuniform character scale, spatially varying text orientation,
      and the interference between text lines. In order to address these problems, we
      propose a new cost function that considers the interactions between text lines
      and the curvilinearity of each text line. Precisely, we achieve this goal by
      introducing normalized measures for them, which are based on an estimated line
      spacing. We also present an optimization method that exploits the properties of
      our cost function. Experimental results on a database consisting of 853
      handwritten Chinese document images have shown that our method achieves a
      detection rate of 99.52% and an error rate of 0.32%, which outperforms
      conventional methods.

PMID- 21896388
TI  - Spatially adaptive block-based super-resolution.
AB  - Super-resolution technology provides an effective way to increase image
      resolution by incorporating additional information from successive input images
      or training samples. Various super-resolution algorithms have been proposed based
      on different assumptions, and their relative performances can differ in regions
      of different characteristics within a single image. Based on this observation, an
      adaptive algorithm is proposed in this paper to integrate a higher level image
      classification task and a lower level super-resolution process, in which we
      incorporate reconstruction-based super-resolution algorithms, single-image
      enhancement, and image/video classification into a single comprehensive
      framework. The target high-resolution image plane is divided into adaptive-sized
      blocks, and different suitable super-resolution algorithms are automatically
      selected for the blocks. Then, a deblocking process is applied to reduce block
      edge artifacts. A new benchmark is also utilized to measure the performance of
      super-resolution algorithms. Experimental results with real-life videos indicate
      encouraging improvements with our method.

PMID- 21896389
TI  - A generalized logarithmic image processing model based on the gigavision sensor
      model.
AB  - The logarithmic image processing (LIP) model is a mathematical theory providing
      generalized linear operations for image processing. The gigavision sensor (GVS)
      is a new imaging device that can be described by a statistical model. In this
      paper, by studying these two seemingly unrelated models, we develop a generalized
      LIP (GLIP) model. With the LIP model being its special case, the GLIP model not
      only provides new insights into the LIP model but also defines new image
      representations and operations for solving general image processing problems that
      are not necessarily related to the GVS. A new parametric LIP model is also
      developed. To illustrate the application of the new scalar multiplication
      operation, we propose an energy-preserving algorithm for tone mapping, which is a
      necessary step in image dehazing. By comparing with results using two state-of
      the-art algorithms, we show that the new scalar multiplication operation is an
      effective tool for tone mapping.

PMID- 21896390
TI  - Low-complexity video coding based on two-dimensional singular value
      decomposition.
AB  - In this paper, we propose a low-complexity video coding scheme based upon 2-D
      singular value decomposition (2-D SVD), which exploits basic temporal correlation
      in visual signals without resorting to motion estimation (ME). By exploring the
      energy compaction property of 2-D SVD coefficient matrices, high coding
      efficiency is achieved. The proposed scheme is for the better compromise of
      computational complexity and temporal redundancy reduction, i.e., compared with
      the existing video coding methods. In addition, the problems caused by frame
      decoding dependence in hybrid video coding, such as unavailability of random
      access, are avoided. The comparison of the proposed 2-D SVD coding scheme with
      the existing relevant non-ME-based low-complexity codecs shows its advantages and
      potential in applications.

PMID- 21896391
TI  - An investigation of dehazing effects on image and video coding.
AB  - This paper makes an investigation of the dehazing effects on image and video
      coding for surveillance systems. The goal is to achieve good dehazed images and
      videos at the receiver while sustaining low bitrates (using compression) in the
      transmission pipeline. At first, this paper proposes a novel method for single
      image dehazing, which is used for the investigation. It operates at a faster
      speed than current methods and can avoid halo effects by using the median
      operation. We then consider the dehazing effects in compression by investigating
      the coding artifacts and motion estimation in cases of applying any dehazing
      method before or after compression. We conclude that better dehazing performance
      with fewer artifacts and better coding efficiency is achieved when the dehazing
      is applied before compression. Simulations for Joint Photographers Expert Group
      images in addition to subjective and objective tests with H.264 compressed
      sequences validate our conclusion.

PMID- 21896392
TI  - Robust through-the-wall radar image classification using a target-model alignment
      procedure.
AB  - A through-the-wall radar image (TWRI) bears little resemblance to the equivalent
      optical image, making it difficult to interpret. To maximize the intelligence
      that may be obtained, it is desirable to automate the classification of targets
      in the image to support human operators. This paper presents a technique for
      classifying stationary targets based on the high-range resolution profile (HRRP)
      extracted from 3-D TWRIs. The dependence of the image on the target location is
      discussed using a system point spread function (PSF) approach. It is shown that
      the position dependence will cause a classifier to fail, unless the image to be
      classified is aligned to a classifier-training location. A target image alignment
      technique based on deconvolution of the image with the system PSF is proposed.
      Comparison of the aligned target images with measured images shows the alignment
      process introducing normalized mean squared error (NMSE) <= 9%. The HRRP
      extracted from aligned target images are classified using a naive Bayesian
      classifier supported by principal component analysis. The classifier is tested
      using a real TWRI of canonical targets behind a concrete wall and shown to obtain
      correct classification rates >= 97%.

PMID- 21896393
TI  - Hybrid ant colony-genetic algorithm (GAAPI) for global continuous optimization.
AB  - Many real-life optimization problems often face an increased rank of
      nonsmoothness (many local minima) which could prevent a search algorithm from
      moving toward the global solution. Evolution-based algorithms try to deal with
      this issue. The algorithm proposed in this paper is called GAAPI and is a
      hybridization between two optimization techniques: a special class of ant colony
      optimization for continuous domains entitled API and a genetic algorithm (GA).
      The algorithm adopts the downhill behavior of API (a key characteristic of
      optimization algorithms) and the good spreading in the solution space of the GA.
      A probabilistic approach and an empirical comparison study are presented to prove
      the convergence of the proposed method in solving different classes of complex
      global continuous optimization problems. Numerical results are reported and
      compared to the existing results in the literature to validate the feasibility
      and the effectiveness of the proposed method. The proposed algorithm is shown to
      be effective and efficient for most of the test functions.

PMID- 21896394
TI  - Geometric decision tree.
AB  - In this paper, we present a new algorithm for learning oblique decision trees.
      Most of the current decision tree algorithms rely on impurity measures to assess
      the goodness of hyperplanes at each node while learning a decision tree in top
      down fashion. These impurity measures do not properly capture the geometric
      structures in the data. Motivated by this, our algorithm uses a strategy for
      assessing the hyperplanes in such a way that the geometric structure in the data
      is taken into account. At each node of the decision tree, we find the clustering
      hyperplanes for both the classes and use their angle bisectors as the split rule
      at that node. We show through empirical studies that this idea leads to small
      decision trees and better performance. We also present some analysis to show that
      the angle bisectors of clustering hyperplanes that we use as the split rules at
      each node are solutions of an interesting optimization problem and hence argue
      that this is a principled method of learning a decision tree.

PMID- 21896395
TI  - Abstracts of the 23rd Annual Conference of the International Society of
      Environmental Epidemiology (ISEE). September 13 - 16, 2011, Barcelona, Spain.
AB  - The International Society for Environmental Epidemiology (ISEE) is an
      international organization with almost 1000 members from more than 60 countries.
      The annual international conference brings together many members and non-members
      and provides an excellent forum for the discussion of problems and benefits
      related to the environment and human health. Specific themes for the 23rd Annual
      Conference include: Sustainable transport and health: Impact of transport on
      health and approaches to reduce health impacts, Impact of climate change: from
      water scarcity to Saharan dust episodes, Early exposure - later life: in utero
      and early life exposures and effects in later life, New methods and technologies.

PMID- 21896396
TI  - Air pollution and acute respiratory response in a panel of asthmatic children
      along the U.S.-Mexico border.
AB  - BACKGROUND: Concerns regarding the health impact of urban air pollution on
      asthmatic children are pronounced along the U.S.-Mexico border because of rapid
      population growth near busy border highways and roads. OBJECTIVES: We conducted
      the first binational study of the impacts of air pollution on asthmatic children
      in Ciudad Juarez, Mexico, and El Paso, Texas, USA, and compared different
      exposure metrics to assess acute respiratory response. METHODS: We recruited 58
      asthmatic children from two schools in Ciudad Juarez and two schools in El Paso.
      A marker of airway inflammation [exhaled nitric oxide (eNO)], respiratory symptom
      surveys, and pollutant measurements (indoor and outdoor 48-hr size-fractionated
      particulate matter, 48-hr black carbon, and 96-hr nitrogen dioxide) were
      collected at each school for 16 weeks. We examined associations between the
      pollutants and respiratory response using generalized linear mixed models.
      RESULTS: We observed small but consistent associations between eNO and numerous
      pollutant metrics, with estimated increases in eNO ranging from 1% to 3% per
      interquartile range increase in pollutant concentrations. Effect estimates from
      models using school-based concentrations were generally stronger than
      corresponding estimates based on concentrations from ambient air monitors. Both
      traffic-related and non-traffic-related particles were typically more robust
      predictors of eNO than was nitrogen dioxide, for which associations were highly
      sensitive to model specification. Associations differed significantly across the
      four school-based cohorts, consistent with heterogeneity in pollutant
      concentrations and cohort characteristics. Models examining respiratory symptoms
      were consistent with the null. CONCLUSIONS: The results indicate adverse effects
      of air pollution on the subclinical respiratory health of asthmatic children in
      this region and provide preliminary support for the use of air pollution monitors
      close to schools to track exposure and potential health risk in this population.

PMID- 21896397
TI  - Case report: supraventricular arrhythmia after exposure to concentrated ambient
      air pollution particles.
AB  - CONTEXT: Exposure to air pollution can result in the onset of arrhythmias. CASE
      PRESENTATION: We present a case of a 58-year-old woman who volunteered to
      participate in a controlled exposure to concentrated ambient particles. Twenty
      minutes into the exposure, telemetry revealed new onset of atrial fibrillation.
      The exposure was discontinued, and she reverted to normal sinus rhythm
      approximately 2 hr later. No abnormality was evident on the volunteer's
      laboratory examination or echocardiography that could explain an increased risk
      for supraventricular arrhythmia. DISCUSSION: Epidemiologic evidence strongly
      supports a relationship between exposure to air pollutants and cardiovascular
      disease, but population-level data are not directly relevant to the clinical
      presentation of individual cases. To our knowledge, this is the only case report
      of an individual suffering an episode of atrial fibrillation after exposure to an
      air pollutant. The resolution of the arrhythmia with termination of the particle
      exposure further supports a causal relationship between the two. RELEVANCE TO
      CLINICAL PRACTICE: Exposure to air pollution, including particulate matter, may
      cause supraventricular arrhythmias.

PMID- 21896398
TI  - [Eating habits of children and adolescents with diabetes in Libreville (Gabon)].
AB  - AIM: the nutritional intake required for normal growth and development is similar
      among children with diabetes and healthy children. Nonetheless, for children with
      diabetes, food intake must also be correlated with their insulin treatment plan
      and level of physical activity. The objective of this work was to identify the
      eating habits of the children and adolescents followed in the National Diabetes
      Center in Libreville. PATIENTS AND METHODS: this prospective survey was conducted
      from November 1, 2008, through January 30, 2009, at the National Diabetes Center
      of the Libreville Hospital Center. RESULTS: during the study period, 21 children
      and adolescents were treated at our center. The sex ratio was 1:1, and the mean
      age was 14.7 years. The mean body mass index (BMI) was 18.5 kg/m(2). Mean age at
      diagnosis was 9.6 years. All the children received insulin; two had two
      injections daily and the other 19 (90.4%), three a day. Three children never ate
      breakfast; 17 "often" drank some milk, and 18 ate some bread. Twenty children
      "often" ate a starch and chicken at lunch, five others "often" had vegetables
      then. Healthy planned snacks were not eaten by 57% of the subjects, although 24%
      reported "nibbling" between meals "sometimes". In addition to water, 67% of the
      patients drank diet Coke. CONCLUSION: few children complied with the diet
      strictly, because their families could not afford to buy all the recommended
      food. Effective access to appropriate local food is essential. All patients
      should discuss their preferred foods with the doctor or dietician, so that their
      insulin treatment can be adapted appropriately to the food.

PMID- 21896400
TI  - Dermal fibrosis related to combination chemotherapy with carboplatin and
      gemcitabine.

PMID- 21896399
TI  - [Psychosocial impact of cancer on Moroccan adolescent and young adult: experience
      of National Institute of Oncology of Rabat].
AB  - Cancer is an uncommon disease; its imaginary concept is very particularly on
      adolescent and young adults. It disturbs their lives on the whole. The purpose of
      this study is to describe the specific psychosocial effects of cancer on
      adolescent and young adults in Moroccan population in order to help physicians
      educate and counsel future young patients and their families. During the period
      from January to July 2009, patients aged between 15 and 30 years with
      histologically confirmed cancer, were prospectively interviewed by a
      questionnaire covering socio-epidemiological characteristics, repercussions of
      disease on physical, psychic, sexual and religious practices. The aim of this
      study is to determine the impact of cancer, particularly on this young North
      African population, which is underrepresented in the psychosocial cancer
      literature.

PMID- 21896401
TI  - Acute generalized exanthematous pustulosis-like drug eruption induced by
      pemetrexed.

PMID- 21896402
TI  - [Somatostatin in breast cancer].
AB  - In man, somatostatin is a hormone mostly produced by hypothalamus. It plays
      different parts in hormonal regulation through many specific receptors in human
      body. It has also two interesting actions such as an anti-secretory activity,
      mostly on the gastrointestinal system and an antiproliferative action on tumor
      cells. Many synthetic somatostatin analogues, more stable than the natural one,
      have been developed and are already used in digestive surgery to treat
      postoperative digestive fistula. Also, the development of specific polyclonal
      antibodies allowed the identification of five specific somatostatin receptors and
      their localization in different cell species. The presence of the five receptors
      in breast cancer cells has than been demonstrated. The purpose of this literature
      review is to clarify the potential antitumor effect of somatastatin analogues in
      breast cancer; its use as a preventive agent on lymphorrhea after breast surgery
      and its employment in imaging for early breast cancer detection.

PMID- 21896403
TI  - [Virulence factors in Pseudomonas aeruginosa: mechanisms and modes of
      regulation].
AB  - Pseudomonas aeruginosa is a bacterium responsible for severe nosocomial
      infections, life-threatening infections in immunocompromised persons, and chronic
      infections in cystic fibrosis patients. The bacterium's virulence depends on a
      large number of cell-associated and extracellular factors. The virulence factors
      play an important pathological role in the colonization, the survival of the
      bacteria and the invasion of tissues. There are two types of virulence factors:
      (1) factors involved in the acute infection: these factors are either on the
      surface of P. aeruginosa, either secreted. The pili allow adherence to the
      epithelium. The exoenzyme S and other adhesins reinforce the adherence to
      epithelial cells. The exotoxin A is responsible of tissue necrosis. Phospholipase
      C is a thermolabile haemolysin. The pathogenic role of exoenzyme S is
      attributable to the disruption of normal cytoskeletal organization, the
      destruction of immunoglobulin G and A, leads to depolymerization of actin
      filaments and contributes to the resistance to macrophages. P. aeruginosa
      produces at least four proteases causing bleeding and tissue necrosis; (2)
      factors involved in the chronic infection: siderophores (pyoverdin and
      pyochelin), allow the bacteria to multiply in the absence of ferrous ions. The
      strains isolated from patients with cystic fibrosis have a pseudocapsule of
      alginate that protects the bacterium from phagocytosis, dehydration and
      antibiotics. Moreover, it improves adherence to epithelial cells forming a
      biofilm. Two different types of regulation systems control the expression of the
      majority of these virulence factors: the two-component transcriptional regulatory
      system and the quorum sensing system. These two mechanisms are necessary to the
      survival and the proliferation of this microorganism in the host.

PMID- 21896404
TI  - [Inherited tubular renal acidosis].
AB  - Renal tubular acidosis (RTA) is a tubulopathy characterized by metabolic acidosis
      with normal anion gap secondary to abnormalities of renal acidification. RTA can
      be classified into four main subtypes: distal RTA, proximal RTA, combined
      proximal and distal RTA, and hyperkalemic RTA. Distal RTA (type 1) is caused by
      the defect of H(+) secretion in the distal tubules and is characterized by the
      inability to acidify the urine below pH 5.5 during systemic acidemia. Proximal
      RTA (type 2) is caused by an impairment of bicarbonate reabsorption in the
      proximal tubules and characterized by a decreased renal bicarbonate threshold.
      Combined proximal and distal RTA (type 3) secondary to a reduction in tubular
      reclamation of bicarbonate and an inability to acidify the urine in the face of
      severe acidemia. Hyperkalemic RTA (type 4) may occur as a result of aldosterone
      deficiency or tubular insensitivity to aldosterone. Clinicians should be alert to
      the presence of RTA in patients with an unexplained normal anion gap acidosis,
      hypokalemia, recurrent nephrolithiasis and nephrocalcinosis. The mainstay of
      treatment of RTA remains alkali replacement.

PMID- 21896405
TI  - [Antiphospholipid syndrome diagnosis: an update].
AB  - The antiphospholipid syndrome (APS) is characterized by arterial and/or venous
      thrombosis and pregnancy morbidity in association with the persistent presence of
      autoantibodies called antiphospholipid antibodies (APAs). APAs are a
      heterogeneous group of circulating autoantibodies that can be detected either by
      phospholipid-dependent coagulation test for lupus anticoagulant (LA) or ELISA
      test for anticardiolipin and anti-beta2GPI antibodies. In 2006, the revised
      criteria for the diagnosis of APS introduce the anti-beta2GPI antibodies as a new
      biological criterion and highlight the necessity to increase the interval between
      two positive APA test from 6 to 12 weeks. However, despite these updated
      criteria, the diagnosis of APS remains challenging and we proposed here to make
      an overview of the latest evolution in the diagnosis of this syndrome.

PMID- 21896406
TI  - HLA-B*27 allele associated to Behcet's disease and to anterior uveitis in
      Moroccan patients.
AB  - Human leukocyte antigen HLA-B51 is the most strongly associated gene with Behcet
      disease (BD) in different ethnic populations. We analyze the influence of HLA-B
      alleles in BD predisposition in Moroccan population and its association with
      clinical manifestations. The HLA-B phenotype frequencies were analyzed by
      serologic HLA class I typing and by polymerase chain reaction sequence-specific
      oligonucleotide (PCR-SSO) reverse dot blot hybridization in 120 unrelated
      Moroccan patients: all of whom fulfilled the international study group criteria
      for Behcet's disease, and in 112 ethnically matched healthy controls. Besides HLA
      B*51 allele (20%), a significant increased frequency of the HLA-B*27 allele was
      found in Moroccans patients with Behcet's disease when compared to controls
      (13.3% of patients versus 2.7% of controls, chi square = 8.75, OR = 5.59, 95% IC
      [1.58-19.75] and particularly in the patients who presented an anterior uveitis
      (25% vs. 5.5%, p < 0.005).

PMID- 21896407
TI  - [Morquio A disease: clinical and molecular study of Tunisian patients].
AB  - Type IVA mucopolysaccharidosis or Morquio A disease is a lysosomal storage
      disease, autosomal recessive, caused by deficiency of the N-acetylgalactosamine-6
      sulfate sulfatase or GALNS. The severe phenotype is characterized by a severe
      skeletal dysplasia without any mental retardation. The aim of this study was to
      propose a strategy of molecular and prenatal diagnosis of this pathology. A
      molecular study was carried out on 7 patients MPS IVA issued from 5 unrelated
      families recruited from different Tunisian regions. All the patients were
      offspring of consanguineous marriages. The clinical and biologic study confirmed
      the diagnosis of MPS IVA within the 7 studied patients. Three GALNS mutations
      were identified by molecular analysis: IVS1+1G>A, G66R and A85T. The unions
      between Tunisian relatives are important and increase the Morquio A incidence in
      Tunisia. The identification of GALNS mutations in the Tunisian population permits
      better understanding of the Morquio A phenotype, a reliable genetic counselling
      and a molecular prenatal diagnosis to Tunisian at-risk relatives.

PMID- 21896408
TI  - [Evaluation of the performances of the UF-1000i((r)) automated urine analyzer].
AB  - The purpose of this study was the evaluation of the UF 1000i((r)) automated urine
      analyzer (bioMerieux((c))).The coefficients of variation (CV) for the
      repeatability of the red blood cell (RBC), white blood cell (WBC) and bacteria
      counts were overall concordant with those announced by the supplier. However, for
      low concentrations, the CV for the repeatability for concentrations of 10(3)
      RBC/mL, 10(3) WBC/mL and 5*10(3) UA/mL were respectively of 26, 18 and 36% and
      thus higher than the CV (10%) reported for each of the three parameters by the
      supplier. Reproducibility results agreed with those given by the supplier (10%).
      The linearity range was different from that reported by the supplier and was
      shifted by a factor 10 for WBC and bacteria high concentrations. Cross
      contamination between samples was prevented by using the washing program
      recommended by the supplier which however led to a lower analysis frequency (80
      samples per hour). Detection limits were of 5,7*10(1) RBC/mL, 5,7*10(1) WBC/mL
      and 1,6*10(4) UA/mL respectively for the RBC, WBC and bacteria. Quantification
      limits found in this study were of 1,3*10(3) RBC/mL, 1,7*10(3) WBC/mL, 5,1*10(3)
      UA/mL. An overestimation of the RBC count was observed within the range of
      5*10(3) to 2*10(4) RBC/mL. Beyond this concentration range, the concordance is
      good. The correlation is poor within this range and good for higher
      concentrations. For WBC, concordance and correlation were satisfactory over the
      whole range tested.

PMID- 21896409
TI  - [Assessment of AFP in amniotic fluid: comparison of three automated techniques].
AB  - Ultrasound scanning is useful to detect neural tube defect (NTD) but scarcely
      distinguished between closed NTD and open NTD, which had very different
      prognosis. An amniotic fluid punction is thus mandatory to search for an increase
      in alpha foeto protein (AFP) levels and for the presence of acetylcholinesterase
      which identified open NTD. However, AFP levels fluctuate both with the
      gestational age and the assay used. Our aim was to establish normative values for
      AFP in amniotic fluid in the second half of pregnancy using three different
      immunoassays and to improve their clinical relevance. Amniotic fluid punctions
      were performed on 527 patients from 9 week of gestation (WG) to 37 WG either for
      maternal age, Trisomy 21 screening, increase in nucal translucency (control
      group, n = 527) or for suspicion of neural tube defect or abdominal defect (n =
      5). AFP was measured using the immunoassay developed for serum AFP on the Access
      2 system, the Immulite 2000 and the Advia Centaur. Results were expressed in
      ng/ml, multiple of the median (MoM) and percentiles. AFP decrease by 1.5 fold
      between 9 and 19 WG. When NTD was suspected, an increase in anmniotic AFP was
      observed (from 2.5 MoM to 9.3 MoM) confirming an open NTD. In conclusion, the
      assay developed on those 3 automates is suitable for the measurement of AFP in
      amniotic fluid.

PMID- 21896410
TI  - Real time PCR for fast detection of the angiotensinogen polymorphisms.
AB  - OBJECTIVE: to develop a rapid and reliable real-time PCR to detect polymorphisms
      of angiotensinogen (AGT), to compare the two methods of MS-PCR (Mutagenically
      Separated PCR) and real-time PCR to determine three polymorphisms of the
      angiotensinogen gene M235T, the A (-6) G and A (-20) C. METHODS: the method of
      real-time PCR was developed on the PLC Roche LightCycler1 with SYBR Green I. We
      used two sense primers and a primer nonsense. Detection of polymorphisms of
      angiotensinogen gene was performed by comparing the melting curves. RESULTS: the
      DNA samples were analyzed by two methods: real-time PCR and MS-PCR. In our study,
      no differences were found between the two techniques. DISCUSSION: The real-time
      PCR is a rapid and reliable method for detecting gene polymorphisms on the AGT
      M235T, the A (-6) G and A (-20) C. CONCLUSION: this method of real-time PCR is a
      reliable genetic test, which is fast and cheap and can be used in practice to
      study particular polymorphisms of AGT gene associated with cardiovascular
      disease.

PMID- 21896411
TI  - [Automatic platelets numbering with citrate as anticoagulant: is the result
      valid?].
AB  - Platelets count is usually realised on EDTA anticoagulant. This one is sometimes
      able to generate platelets agregats. That is the reason why the first thing to do
      encountering thrombopenia is to check for agregats on blood thin smear. In case
      of positive result, a control can be asked using another anticoagulant. The most
      used is sodium citrate. A correction has to be applied to the automat result
      because blood is diluted in anticoagulant. But no one says those haematological
      automats are exact on citrate as they are on EDTA. That's what we wanted to
      check.

PMID- 21896412
TI  - [An asymptomatic chronic hypokalaemia].
AB  - We report the case of an asymptomatic patient presenting a severe chronic renal
      hypokalaemia. Once being sure of no diuretics use, two hypothesis can be
      mentioned for a normotensive patient presenting an hypokalaemia associated with a
      metabolic alcalosis: Bartter syndrome or Gitelman syndrome. The highlighting of
      low magnesaemia and hypocalciuria strongly concentrates the diagnosis on Gitelman
      syndrome. First, this has been strengthened by the results of renal function
      tests and later it has confirmed by molecular diagnosis with the identification
      of a known homozygous mutation on SLC12A3 gene. In the patient family, the same
      chromosomal abnormality has been found in the young sister. For these two
      patients the treatment ordered is an antikaliuretic diuretic, magnesium and
      potassium supplements. This case shows the difficulty to diagnose Gitelman
      syndrome: it is frequently mistaken for Bartter syndrome. The main differences
      between these two syndromes are magnesaemia and calciuria. Furthemore , patients
      with Gitelman syndrome are often asymptomatic, this explains why prevalence of
      this illness is probably underestimated.

PMID- 21896414
TI  - [Screening of alloantibodies: stability of false positive results as a quality
      indicator].
AB  - Screening of alloantibodies is required before each transfusion. As part of our
      blood bank quality assurance, we have developed a quality indicator to monitor
      these false positive antibody results. We have studied 25.162 samples: sera were
      first screened by automated column agglutination technology (CAT). Positive
      results were found in 1.365 of the 25.162 samples. False positive results, ie
      positive screening test followed by a negative identification, were found in 271
      (20%) cases. In the 116 patients remaining (43%) no factor could be evidenced.
      Interestingly, the percentage of patients with false positive antibody screening
      was stable month after month. In our experience, this percentage is very stable,
      it may be used as an indicator of quality laboratory and its unusual variation
      allows to suspect alterations of the reagents (hemolysis, loss of specificity,
      sensitivity).

PMID- 21896413
TI  - [Diagnostic strategy of metachromatic leukodystrophy in Tunisia].
AB  - We recruited a 44-year-old woman who had a dementia with behavioral and
      personality troubles. A biochemical analysis which includes a qualitative study
      of urinary sulfatides by thin layer chromatography followed by the determination
      of the enzymatic activity of arylsulfatase A (ARSA) was performed. The Molecular
      analysis concerned the research of the most frequent mutations (459 +1 G> A,
      p.P426L, p.I179S). The profile that has revealed the presence of 3-O
      sulfogalactosylceramide fraction was in favor of metachromatic leukodystrophy.
      The activity of arylsulfatase A was collapsed in the index case which confirmed
      the phenotype of the adult form of the diagnosed MLD. The molecular study showed
      the presence of the mutation p.I179S in the homozygous state in the index case.

PMID- 21896415
TI  - [Acute lymphoblastic leukemia with T + PH1 monocytosis: a case report].
AB  - Acute lymphoblastic leukemia Type T PH1 positive (with t (9.22)) are exceptional.
      These effects can occur immediately or in the evolution of chronic myeloid
      leukemia known. We report the case of a patient aged 31 years with acute
      lymphoblastic leukemia T PH1 + cyologiques with cytological atypia. The overall
      appearance of blood and marrow: the signs of dysplasia the presence of a
      monocytic contingent, with blood monocytes evoked a myeloid acute leukemia AL.
      But the immunophenotype was unequivocally in favor of T- acute lymphoblastic
      leukemia with one aspect of lymphoid blasts in morphology and myeloperoxidase
      negative. The karyotype showed the presence of Philadelphia chromosome in all
      mitoses with additional abnormalities (chromosomes 2, 11.16...).

PMID- 21896417
TI  - [Aregenerative anemia and erythrocytes hemighosts: a case report].
AB  - An 11 year old African boy without previous history was hospitalised for fever
      and a severe anaemia (haemoglobin = 55 g/L) with low reticulocyte count. Blood
      smear showed more than 35% of ghost red blood cells which allows the diagnosis of
      G6PD deficiency (< 1% of normal level). Anaemia was demonstrated as haemolytic
      and was associated with a drepanocytosis trait. Aspect of red blood cells on
      blood smear remains important for the diagnosis of congenital or acquired red
      blood cell diseases, even abnormalities are often of low specificity.

PMID- 21896416
TI  - [Identification and characterization of a monoclonal IgM reacting with
      disialylated gangliosides recognizing the CANOMAD syndrome].
AB  - We reported the laboratory phenotype of a monoclonal IgM-lambda against
      disialylated gangliosides, in a 81-year-old man admitted to a neurological
      department because of the progressive development of distal paresthesias, gait
      unsteadiness, difficulty to walk and having falls. Serological studies revealed
      an IgM monoclonal protein with lambda light chain component of MGUS type. IgM
      level was 4 g/L. The positive laboratory studies showed high titers of IgM
      antibodies in excess of 1/10(5) against specific disialylated gangliosides
      including GD1b, GD3, GT1b and GQ1b. There was no serum IgM binding to MAG and
      SGPG/SGLPG. Clonality by in-house immunodot of ganglioside antibodies was
      demonstrated using kappa and lambda light chain specific antibodies. Light chain
      subtype of the anti-ganglioside antibody activity and monoclonal IgM was lambda
      subtype. The reactivity at high titers was against gangliosides containing the
      disialosyl epitope. The clinical and laboratory features have been described
      under the acronym CANOMAD: Chronic Ataxic Neuropathy with Ophthalmoplegia, M
      proteins, cold Agglutinins and Disialosyl antibodies. Administration of IVIg
      produced a significant neurological improvement during six years. Then the
      neuropathy became refractory in the IVIg and worsened in severity, a cure by
      Rituximab(r) was established. The patient died from a pneumopathy only two months
      later. Monoclonal IgM binding to disialylated gangliosides have high level of
      specificity for diagnosis of the CANOMAD syndrome.

PMID- 21896418
TI  - [Acute appendicitis due to both Klebsiella pneumoniae and serotype 35B
      Streptococcus pneumoniae, an emergent serotype].
AB  - Streptococcus pneumoniae has been rarely considered as an infectious agent in
      appendicitis. We report a case of a 47-year-old woman with acute appendicitis
      caused both by serotype 35B S. pneumoniae and Klebsiella pneumoniae. The pathway
      of the appendix colonisation remains unclear. It could be explain by direct
      infection via mucosal translocation or by hematogenous spread. Pneumococcal
      appendicitis could progress to perforation more frequently. The use of
      intraoperative samples for management of appendicitis is controversial. But,
      culture with appropriate media is the only mean to isolate bacteria not very
      often encountered in appendicitis and to identify species of epidemiologic
      interest as serotype 35B S. pneumoniae, a non vaccinal serotype resistant to
      penicillin which is considered as a potential emergent pathogen. In the case of
      S. pneumoniae appendicitis, it could be recommended to take complementary
      directed samples to understand its pathophysiology.

PMID- 21896419
TI  - [Proposed recommendations for the practical use of internal quality controls
      (IQC) in a medical biology laboratory].
AB  - We propose a set of recommendations and practices to optimize the use of quality
      control of medical biology examinations. The fundamentals are reviewed:
      definition of a series of analysis, IQC at one or more level, Westgard alert
      rules and rejection, practical remedial actions to take for the technician,
      corrective and preventive actions to be implemented by the biologist. We have
      also formalized three flowcharts to guide the technician in their daily practice
      to ensure analytical quality of investigations carried out. These decision trees
      are the result of the experience submitted by an accredited and professional
      laboratory attentive to the ongoing improvement of IQC. This article can provide
      useful assistance to biologists for accreditation but also aims to foster
      collaboration reliable medical biology laboratory at the appropriate management
      of patients.

PMID- 21896420
TI  - Superimposed segmental manifestation of cherry angiomas.
AB  - Cherry angioma is a common, acquired, vascular proliferation, probably of a
      polygenic mode of inheritance. Segmental manifestation of multiple cherry
      angiomas associated with the development of non-segmental lesions has not yet
      been reported. We describe a 62-year-old Caucasian woman with early formation of
      segmental cherry angiomas after pregnancy, which are superimposed on non
      segmental lesions of later onset after menopause. In this pattern, segmental
      cherry angiomas could be taken as a further example of superimposed segmental
      manifestation of a polygenic skin disorder. Molecular research would be needed to
      confirm this hypothesis.

PMID- 21896421
TI  - Quality of life in melanoma patients during adjuvant treatment with pegylated
      interferon-alpha2b: patients' and doctors' views.
AB  - Treatment of malignant melanoma with IFN-alpha has been associated with
      significant side-effects. The aim of this retrospective monocentric non
      randomized study was first to evaluate the impact on quality of life (QOL) in 30
      melanoma patients treated with once weekly 2 MUg/kg PEG-IFN-alpha2b for 18
      months, and second to examine whether there is a difference in patients' and
      physicians' perception of QOL. Data on QOL were collected by means of the EORTC
      QLQ-C30 questionnaire completed by the patient before consultation at baseline
      and every three months during treatment. A second questionnaire was filled out
      independently by the physician, based on the consultation and patient file. All
      data were routinely collected in an outpatient care unit. At baseline, patients
      had more favorable mean values on almost all dimensions of the EORTC QLQ-C30 than
      follow-up assessments. In comparison to published low-dose IFN-alpha2a data, once
      weekly 2 MUg/kg PEG-IFN-alpha2b was associated with stronger impairment in most
      QOL single dimensions but with almost no differences regarding the global health
      status. QOL documented by physicians was significantly higher than QOL from the
      patients' questionnaires in all QOL dimensions (p<0.05). PEG-IFN-alpha2b has
      measurable effects on QOL. Measuring QOL based only on physicians' patient files
      without explicitly determining patients' assessments leads to a profound
      underestimation of impairment of QOL.

PMID- 21896422
TI  - Squamous cell carcinoma of the scalp associated with human papillomavirus type
      16.

PMID- 21896423
TI  - Recurrence of childhood absence epilepsy as pyknolepsy in adolescence.
AB  - A developmentally normal adolescent boy with a history of childhood absence
      epilepsy presented with recurrence of pyknolepsy after a seven-year period of
      remission. The characteristics of his EEG showed the same 3-Hz generalised spike
      wave discharge as in his previous EEG in childhood. To our knowledge, this is the
      first case report describing recurrence of childhood absence epilepsy as
      pyknolepsy in an adolescent. [Published with video sequences].

PMID- 21896424
TI  - Atypical presentation in Rasmussen encephalitis: delayed late-onset periodic
      epileptic spasms.
AB  - A five-and-a-half-year-old girl started experiencing progressive left hemiparesis
      at age two and a half years. At age five years and four months she started
      presenting clusters of asymmetric periodic epileptic spasms with no
      hypsarrhythmia. The ictal EEG showed periodic, constant and stereotyped
      complexes. Serial brain imaging revealed progressive atrophy of the right
      hemisphere with increased T2 signal on MRI. She underwent a right hemispherotomy,
      and histological examination showed signs of inflammation and features of focal
      cortical dysplasia (FCD). She has been seizure-free for 16 months. This case is
      unique in the following aspects: the presence of typical Rasmussen encephalitis
      features of progressive unilateral brain involvement without seizures, a delay of
      almost three years prior to seizure onset; an atypical seizure type presentation
      with periodic epileptic spasms and the presence of FCD associated with
      inflammatory changes. [Published with video sequences].

PMID- 21896426
TI  - Lamotrigine is favourable for startle-induced seizures.
AB  - Falling due to startle-induced seizures (SISs) often leads to injury. The
      triggers of SIS are mostly unexpected auditory stimuli, which are too common to
      avoid in daily life. As SISs are often refractory to conventional medications,
      effective therapeutic options have to be established. We report a small series of
      six patients treated with lamotrigine (LTG) as add-on therapy. Seizure control
      was improved greatly in three of the six patients, resulting in less restricted
      daily life, but no effect was observed in two and a skin rash developed in one.
      Patient 1 was a 19-year-old man. His seizure comprised of a sudden tonic
      extension of the extremities induced by auditory or visual stimulus. He fell down
      due to SISs, five to ten times a day, with frequent injuries. After adding LTG to
      treatment with valproate (VPA) and clobazam (CLB), SISs were reduced to once a
      month. Patient 2 was a 51-year-old woman. Sudden tonic extension of all limbs
      induced by unexpected sounds frequently threw her down onto the floor. Addition
      of LTG to treatment with CLB, zonisamide and phenytoin reduced her SISs from
      several to less than once a day. Patient 3 was a seven-year-old girl with post
      encephalitic epilepsy. After adjunctive treatment of LTG to VPA, the severity of
      SISs became milder thus avoiding injury, although seizure frequency did not
      decrease. LTG is potentially effective for the treatment of SISs and may prevent
      falling. The addition of LTG treatment dramatically improved the lives of the
      patients presented here and should be considered as an option for startle-induced
      seizures.

PMID- 21896425
TI  - Non-convulsive status epilepticus of frontal origin as the first manifestation of
      Hashimoto's encephalopathy.
AB  - Hashimoto's encephalopathy is an often misdiagnosed, life threatening, condition
      which improves promptly with steroid therapy. Since clinical manifestations are
      heterogeneous and non-specific, the diagnosis is often difficult. Several case
      reports of Hashimoto's encephalopathy presenting with partial or generalised
      seizures are described, but only a few have focused on status epilepticus as the
      first clinical manifestation. We report two patients presenting with repetitive
      and prolonged seizures characterised by progressive reduction in contact and
      reactivity associated with frontal/diffuse polyspike-and-wave activities. This
      condition, which can be interpreted as a form of non-convulsive status
      epilepticus (NCSE) of frontal origin, was refractory to antiepileptic drugs but
      responded promptly to high doses of intravenous steroid treatment. In cases of
      unexplained encephalopathy with EEG documentation of NCSE, the early recognition
      and treatment of Hashimoto's encephalopathy may lead to a favourable prognosis.
      [Published with video sequences].

PMID- 21896427
TI  - [Falls in the elderly: a current issue].

PMID- 21896428
TI  - [Practical aspects of vaccination in elderly subjects].
AB  - The elderly subjects are at high risk of infection due to decreased immune
      responses and institutionalization. Studies show the effectiveness of influenza
      vaccination every year in subjects over 65 years, and pneumococcal vaccination
      every 5 years in patients with risk factors. Vaccinations against diphtheria low
      dose, tetanus, and polio should be renewed every 10 years. Pertussis should be
      catched-up in every adult not vaccinated since more than 10 years. Admission in
      institution, a pre-travel consultation and hospitalization for an infectious
      disease must be an opportunity to offer vaccination, especially among the frail
      elderly subjects with comorbidities.

PMID- 21896429
TI  - [Vitamin D in the elderly: 5 points to remember].
AB  - Vitamin D is a secosteroid hormone. Vitamin D receptors are present in the
      majority of body tissues. The manifestations of hypovitaminosis D - linked to
      dysfunction of target tissues - are various, including osteoporosis, cancer,
      tuberculosis, hypertension, multiple sclerosis, depression, dementia, sarcopenia,
      propensity to fall... The serum 25-hydroxyvitamin D threshold value to avoid
      these adverse health events is around 30 ng/mL. Only 15% of the elderly reach
      this target concentration. For the remaining 85% with no supplements, the
      severity of hypovitaminosis D appears to be a biomarker of chronic diseases and
      of frailty. Conversely, the supplementation for correction of hypovitaminosis D
      positively impacts bone and non-bone morbidities - such as risks of falls and
      fractures - and reduces the mortality rate. A daily intake of at least 800-1,000
      IU supplemental vitamin D(3) per day is the key.

PMID- 21896430
TI  - [How to manage gait and balance disorders among older adults aged 65 years and
      older with mild to moderate dementia in clinical practice?].
AB  - Gait and balance disorders are frequent in demented older adults. Their
      management (i.e., diagnosis, assessment and treatment) is challenging in daily
      practice because of numerous evaluation tests available, difficulties to select
      the most adapted intervention, and the lack of knowledge of physicians and health
      professionals concerning adapted centers to refer their patients to those
      patients. Thus, a working group of experts was organized by the Gerontopole of
      Pays de Loire, France, in December 2010 with the aim to provide clinical
      guidelines for the management of older adults aged 65 years and older with mild
      to moderate dementia with gait and balance disorders. These guidelines provide
      answers to the following questions: 1) Is there gait and/or balance disorders? 2)
      Which specific tests used? and 3) How to treat patients?

PMID- 21896431
TI  - [Beyond to pattern of risk factors in elderly subjects].
AB  - Most falls in the elderly result from an interaction between several risk factors
      in. Interventions targeting risk factors for a fall have been effective in the
      prevention of falls. The aim of this prospective study was to identify pattern of
      risk factors in hospitalized elderly subjects for fall in a geriatric acute care
      unit. METHODS: over a 5-year period, 471 patients hospitalized in the geriatric
      unit of Angers Hospital following a fall were randomly assigned to 471 patients
      without any fall history. The prevalence of risk factors for a fall, and the
      existence of predisposing and precipitating factors were compared between the two
      groups. RESULTS: risk factors for fall, namely gait unsteadiness, hip disorders,
      peripheral neuropathy, convulsions and syncope, were significantly more prevalent
      in the group of fallers compared to the controls. Two faller patterns were
      proposed: (1) patients with depression and receiving benzodiazepine and
      neuroleptic, and (2) patients with poor vision and osteoarticular disorders. Two
      further factors, namely parkinsonism and foot disorders, seemed to be sufficient
      to explain a fall. CONCLUSION: this study for the first time has identified risk
      factors patterns of fall in elderly patients hospitalized in a geriatric acute
      care unit, which can be used to implement diagnosis and treatment strategies.

PMID- 21896432
TI  - [The overestimation of performance: a specific bias of aging?].
AB  - The decline of postural abilities with age leads to increased falls. In this
      study, we suggest that a disturbance in the perception of postural affordances,
      characterized by an overestimation of performance, could be a major risk of falls
      specifically in the elderly. In addition, we test the possible link between the
      overestimation of capabilities and postural balance as we know degraded in the
      elderly. A group of 10 young subjects (M = 24.2 years +/- 2.04) and a group of 10
      elderly subjects (M = 75.9 years +/- 5.7) must evaluate, without action, the
      maximum height of an obstacle that they can stride over. Then their postural
      performances are measured. The results show that, contrary to young people who
      correctly evaluate their performance (difference of 1.75 cm between estimated
      performance and real performance), older participants overestimate their maximum
      height of crossing over (12.5 cm difference between performance and estimated
      real performance). Moreover, the overestimation of performance is associated with
      poor postural stability. The bias of overestimation may stem from a lack of
      updating of motor programs caused by a functional brain change with age and/or
      lack of exercise who reduces updating by trial and error.

PMID- 21896433
TI  - [Geriatric day hospital: what evidence? A systematic review].
AB  - A systematic review of the international literature concerning the organisation
      of the Geriatric Day Hospital (GDH) was performed. From 1987 till now, few papers
      were found describing the activity and the effectiveness of the GDH. All the
      studies comparing specific geriatric approaches to regular medicine demonstrate
      the efficiency of geriatric care, particularly the geriatric assessment. So, with
      a degree of evidence 1a, a better outcome is found for patients undergoing a
      geriatric assessment and intervention, compared to patients having no geriatric
      assessment at all. However, there is no evidence of benefit for the geriatric day
      hospital compared to patients treated in a geriatric ward or other location of
      geriatric care. Moreover, there is no clear consensus on the settings and
      activities of a geriatric day hospital. Terms as day unit, day hospital, day
      care, are used interchangeably and are not always covering the same activity. The
      same remark can be made on the exact composition of the geriatric
      multidisciplinary team and its role. However nurses and paramedical workers are
      always mentioned as all performing geriatric assessment. The diagnostic
      activities on the GDH are seldom described and studied. More information is
      available on rehabilitation activity, often developed in specific patient
      populations such as stroke patients, dementia patients, cardiac patients or
      patients with other chronic diseases. In this selected patient populations
      positive effects on outcome are shown in the GDH (level of evidence 1a). Another
      problem is the heterogeneity of the population. For scientific reason the GDH
      should focus on organising care for specific medical problems. Diseases as
      dementia, stroke, cardiac insufficiency, could be good models to investigate the
      efficiency of geriatric assessment and interventions within the setting of a GDH.

PMID- 21896434
TI  - [The fourteenth autonomous meeting of the Belgian Society of Gerontology and
      Geriatrics].

PMID- 21896435
TI  - [Category-specific deficits in semantic dementia: links between perception and
      semantic knowledge].
AB  - The nature of knowledge and its relationship with the perceptual processes are
      among the most central issues in the study of human cognition. Should knowledge
      be abstract, then semantic memory and perception should be relatively
      independent. On the contrary, if knowledge is sensory-dependent, then memory and
      perception should be very close. The first view is supported by the multiple
      system approach of memory, whereas the second view is supported by the single
      store memory theories. One way to study these links is through the category
      specific impairment and the sensory-functional theory (SFT). Category-specific
      impairment is generally observed for living items compared to artefacts. The SFT
      explains this deficit by defining living items as essentially based on
      perception. In the abstract view of knowledge, a living deficit should be related
      to a deficit in processing sensory knowledge. On the opposite, the sensory
      dependent view states that this deficit results from perception impairment. This
      article focuses on the relations between knowledge and perception in semantic
      dementia (SD). SD is characterized by a progressive loss of semantic knowledge,
      making it particularly interesting to study. This article first focuses on the
      SFT, to explain the category-specific impairment. The issue of perceptual
      processing in SD is then reviewed from the lowest level (senses) to the highest
      level of perception (multimodal integration). The data demonstrated normal
      perception for these patients. However, visual integration appeared to be
      impaired for existing knowledge. This result is discussed in relation with a
      possible involvement of the anterior temporal lobes. These regions are known to
      be the most vulnerable in SD. Recently these regions have also been shown to be
      involved in the multimodal integration. Taken together, these data suggest that
      perception and knowledge could be linked and partially explained by the SFT.
      Finally, the data support the sensory-dependent approaches of memory.

PMID- 21896436
TI  - [Cognitive aging in schizophrenia].
AB  - The development of studies of aging patients with schizophrenia results from
      their increasing life expectancy in accordance with that of the general
      population, but remains far below that one. Studies devoted to cognitive deficits
      in these patients globally show various complex cognitive deficits, which usually
      remain stable in their evolution. However, some patients develop a severe
      cognitive decline after 65 years, following a long institutionalization. Complex
      cognitive functions particularly deserve to be systematically explored in
      patients presenting with cognitive complaints and/or communication difficulties.
      As an example, we present the case report of a patient showing a theory of mind
      deficit.

PMID- 21896437
TI  - [Old patients suffering from long-standing schizophrenia: clinical aspects].
AB  - Although some patients suffering from schizophrenia experience an age-related
      amelioration, a great number of people who are entering old age suffer from long
      standing schizophrenia. These patients show specific psychiatric and somatic
      problems that must be taken into account. Firstly, some display high levels of
      all schizophrenic symptoms, while others experience changes in the symptom
      profile with aging, i.e. a reduction in positive symptoms and an increase in
      negative ones. Secondly, the occurrence of significant depressive symptoms among
      elderly patients with schizophrenia is well recognized. Thirdly, in recent years,
      studies have begun to shed more light on the trajectories of cognitive impairment
      of these patients in old age. Lastly, aged persons with schizophrenia often have
      side effects due to long-term antipsychotic medications and medical co-morbidity,
      more untreated somatic disorders (diabetes, cardiovascular diseases) and higher
      mortality rates. These may be the result of both lifestyle factors and lack of
      adequate medical care. Levels of adaptive functioning and quality of life are
      closely associated with clinical and social factors. Thus, we must consider all
      these different aspects in order to effectively manage the therapeutic and
      service needs of these patients.

PMID- 21896438
TI  - [Speech and regulation of behavior: the works of LS Vygosty and AR Luria].
AB  - The role of speech in the regulation of behavior was described in child
      psychology by LS Vygotsky and AR Luria in the Soviet Union during the twenties,
      and extended to neuropsychology by Luria after the World War II. According to
      Vygotsky, man built up " psychological tools " on the model of material tools to
      extend his natural capacities. Psychological tools, such as language, are
      symbolic systems from social origin, which control activity and behavior, and
      convert natural cognitive processes into higher cortical functions. Therefore
      child's development is embedded into particular social relationships. First
      communicational speech then inner speech plays a major role in the regulation of
      behavior in man: at first it goes with action, then precedes it, and finally
      replaces it. A willful action is thus an action largely controlled by inner
      speech, especially in novel and complex tasks, but the properties of inner speech
      differ from those of communicational speech. Assessment of the role of speech on
      the regulation of action and behavior should be part of the neuropsychological
      examination of frontal lobe functions. It also could be useful to assess the
      ability of patients to participate in cognitive rehabilitation, particularly in
      Alzheimer's disease.

PMID- 21896439
TI  - [Difficulties, coping strategies and satisfactions in family caregivers of people
      with Alzheimer's disease].
AB  - Supporting family carers is likely to remain at the forefront of community care
      policy in dementia care for the foreseeable future. However, despite extensive
      research in the area, there is little evidence for the effectiveness of current
      interventions. Focus being placed almost exclusively on the caregivers' burden,
      at the expense of skills they develop and of satisfactions they experience,
      partly explains such an impasse. The aim of this study was to use Nolan's
      approach and methodology for a holistic assessment of a sample of French
      carers'needs (N  = 74). Our study constitutes a first step toward a translation
      and validation of the Carers Assessment of Difficulties Index, Carers Assessment
      of Managing Index, and the Carers Assessment of Satisfactions Index (CADI-CAMI
      CASI). It describes how carers manage the difficulties of the caring situation
      and what satisfactions they may find in their role. Our results should encourage
      larger studies aimed at validating Nolan's methodology, as well as defining and
      promoting professional efficient interventions as they are based on a partnership
      that allows caregivers to define themselves "what works" and what is gratifying.

PMID- 21896440
TI  - [Ewing sarcoma in a 12-year-old Gabonese boy].
AB  - Ewing sarcoma is a primary malignant bone tumor rarely observed in black
      populations. We report a case of Ewing sarcoma in a 12-year-old boy, manifested
      by pain in the lower limbs and pelvis, limping while walking, with functional
      disability and visual disorders developing over a 2-year period, from 2005
      through 2007. The child was transferred for care to South Africa where a biopsy
      bone was taken and analyzed. The histological slices showed clusters of small
      round cells, sometimes with indistinct or eosinophilic cytoplasm, oval vesicular
      nuclei, and fine chromatin. These images were compatible with neoplastic
      proliferation of small round cells of the Ewing tumor type. We use this case to
      review the literature and discuss the circumstances of onset and methods of
      diagnosis.

PMID- 21896441
TI  - [Surgical approaches to hysterectomy].
AB  - OBJECTIVES: this study aims to assess the frequency, complications and advantages
      of each of the three principal approaches to hysterectomies: abdominal, vaginal,
      and laparoscopic. PATIENTS AND METHOD: this prospective study analyses a
      consecutive series of 78 hysterectomies for benign disease (myomas and
      precancerous lesions of the cervix) in the gynaecological surgery department of
      Libreville Hospital Centre from March 1, 2006, to November, 2010. We excluded
      cases of genital prolapsus, invasive uterine cancer, and hysterectomy during
      pregnancy or delivery. Data were collected from the surgical registers and
      reports and from patients' files. RESULTS: the frequency of abdominal
      hysterectomy was about 39% (31 cases), and that of vaginal hysterectomy 61% (31
      cases); laparoscopic assistance was involved in 20.58% (14 cases). The women's
      mean age was 46  years (range: 45 to 60  years). Mean parity was 5.5 (range: 0 to
      9). Overall, 30% of the patients had previously undergone pelvic surgery by the
      abdominal route. Two wounds, one of the bladder and the other of the uterus,
      comprised the surgical morbidity. No deaths occurred. CONCLUSION: the surgeon's
      experience with the vaginal route, sometimes with laparoscopic assistance,
      resulted in limited use of the abdominal route.

PMID- 21896442
TI  - [Fatty liver and hepatitis C virus infection].
AB  - Hepatitis C virus infection is a common liver disease worldwide, leading to the
      development of steatosis, cirrhosis and hepatocellular carcinoma. In patients
      with chronic hepatitis C virus infection the prevalence of steatosis has been
      estimated to be about 55%. Development of steatosis is due to both viral and
      metabolic factors. Hepatitis C virus proteins moderate a number of intracellular
      pathways, however, further studies are required to understand these mechanisms.
      Obesity and insulin resistance may allow the virus to resist antiviral treatment.
      This review discusses the relationship among steatosis, insulin resistance and
      the response to antiviral therapy.

PMID- 21896443
TI  - [Cardiorenal syndromes].
AB  - Cardiac and kidney diseases are very common, and increasingly coexist.
      Classification for cardiorenal syndrome and for its specific subtypes has been
      developed and published recently by a consensus group of the Acute Dialysis
      Quality Initiative. Cardiorenal syndromes have been classified according to
      whether the impairment of each organ is primary, secondary or whether heart and
      kidney dysfunction occurs simultaneously as a systemic disease. The different
      syndromes were classified into five subtypes. Type-1: acute cardiorenal syndrome:
      an abrupt worsening of cardiac function leading to acute kidney injury and/or
      dysfunction. Type-2: chronic cardiorenal syndrome: chronic abnormalities in
      cardiac function causing kidney injury and/or dysfunction. Type-3: acute
      renocardiac syndrome: abrupt worsening of kidney function leading to heart injury
      and/or dysfunction. Type-4: chronic renocardiac syndrome: chronic kidney diseases
      leading to heart injury, disease and/or dysfunction. Type-5: secondary
      cardiorenal syndrome: acute or chronic systemic diseases leading to simultaneous
      injury and/or dysfunction of heart and kidney. The identification of patients and
      the pathophysiological mechanisms underlying each syndrome subtype will help
      cardiologists, nephrologists and physicians working on intensive care units to
      characterize groups of their patients with cardiac and renal impairment and to
      provide a more accurate treatment for them.

PMID- 21896444
TI  - [Interpretation of highly sensitive troponin assays: acute or chronic myocardial
      damage?].
AB  - Troponin is the first choice in the diagnosis of acute myocardial infarction.
      Correct interpretation is challenging, because high sensitive troponin tests used
      today detect even the smallest cardiac damage. METHODS: High sensitive troponin T
      (Roche) and troponin I (Mitsubishi Pathfast) and creatine-kinase activity were
      measured in 20 patients, each having two samples with the time lapse 3-9 hours.
      RESULTS: In the group without acute myocardial infarction (n = 10) no significant
      increase in creatine-kinase and creatine-kinase-MB levels were seen, and the mild
      raise of troponins was due to other cardiovascular problems (atrial fibrillation,
      paroxysmal supraventricular tachycardia). With acute myocardial infarction (n =
      10) a dramatic increase of troponin levels was found in the second samples, and
      also an increase of creatine-kinase and creatine-kinase-MB activity. According to
      Fischer-probe a twofold or higher increase of troponin implies 19-times higher
      risk of acute myocardial infarction in the case of troponin T and 8-times odds
      ratio at troponin I. CONCLUSIONS: The patient's accompanying diseases should
      always be considered. If the troponin level is elevated, the measurement should
      be repeated within 3-6 hours. When troponin shows at least a twofold increase and
      the patient has chest pain or positive ECG, AMI is likely, and the patient needs
      special medical care. Although the first troponin level might be elevated if
      accompanying diseases cause chronic cardiac damage, it can be differentiated by a
      second troponin measurement.

PMID- 21896445
TI  - [Attitudes of freshman medical students towards education in communication
      skills].
AB  - In their institute authors teach medical communication skills in three languages
      (Hungarian, English and German) for medical students in the first year of their
      studies. In order to improve teaching methods, authors wanted to explore the
      attitudes of students towards the communication skills learning. For this purpose
      authors applied the Communication Skills Attitudes Scale created by Rees et al.,
      which is an internationally accepted and well adaptable instrument. AIMS: In this
      survey authors wanted to validate the Hungarian and German version of the
      Communication Skills Attitudes Scale. In addition, their aim was to analyze
      possible differences between the attitudes of each of the three medical teaching
      programs. METHODS: Questionnaires were filled anonymously at the beginning of the
      practices. Principal component analysis with varimax rotation was performed to
      evaluate the attitudes using the SPSS 10.5 version for analysis. RESULTS: Authors
      created a model consisting of 7 factors. Factors were the following: 1: respect
      and interpersonal skills; 2: learning; 3: importance of communication within
      medical profession; 4: excuse; 5: counter; 6: exam; 7: overconfidence. It was
      found that students had mainly positive attitudes. Except the learning factor,
      all other factors showed significant differences between the three medical
      teaching programs. CONCLUSIONS: although students had mainly positive attitudes
      toward learning communication skills, there were negative attitudes which can be
      partly modified by improving the teaching methods. However, results may create a
      proper base for further research to help improving communication skills teaching
      methods of the authors.

PMID- 21896446
TI  - [History of arteficial deformation of the human body. V. Selfmutilation, ritual
      mutilation].

PMID- 21896449
TI  - Methods to decrease pharmaceutical drugs in the water system.

PMID- 21896450
TI  - Earthquake, tsunami, and pharmaceutical care in eastern Japan.

PMID- 21896451
TI  - Polypharmacy: In search of an appropriate term.

PMID- 21896452
TI  - Is 60 seconds enough? Can talking pill bottles be used in the community pharmacy
      setting?

PMID- 21896453
TI  - Drug-drug interaction software quality assurance: Lessons learned.

PMID- 21896454
TI  - Mitigating the impact of medication shortages on public health.

PMID- 21896455
TI  - Do remote community telepharmacies have higher medication error rates than
      traditional community pharmacies? Evidence from the North Dakota Telepharmacy
      Project.
AB  - OBJECTIVE: To evaluate the differences in medication dispensing errors between
      remote telepharmacy sites (pharmacist not physically present) and standard
      community pharmacy sites (pharmacist physically present and no telepharmacy
      technology; comparison group). DESIGN: Pilot, cross-sectional, comparison study.
      SETTING: North Dakota from January 2005 to September 2008. PARTICIPANTS: Pharmacy
      staff at 14 remote telepharmacy sites and 8 comparison community pharmacies.
      INTERVENTION: The Pharmacy Quality Commitment (PQC) reporting system was
      incorporated into the North Dakota Telepharmacy Project. A session was conducted
      to train pharmacists and technicians on use of the PQC system. A quality-related
      event (QRE) was defined as either a near miss (i.e., mistake caught before
      reaching patient; pharmacy discovery), or an error (i.e., mistake discovered
      after patient received medication; patient discovery). MAIN OUTCOME MEASURE: QREs
      for prescriptions. RESULTS: During a 45-month period, the remote telepharmacy
      group reported 47,078 prescriptions and 631 QREs compared with 123,346
      prescriptions and 1,002 QREs in the standard pharmacy group. Results for near
      misses (pharmacy discovery) and errors (patient discovery) for the remote and
      comparison sites were 553 and 887 and 78 and 125, respectively. Percentage of
      "where the mistake was caught" (i.e., pharmacist check) for the remote and
      comparison sites were 58% and 69%, respectively. CONCLUSION: This study reported
      a lower overall rate (1.0%) and a slight difference in medication dispensing
      error rates between remote telepharmacy sites (1.3%) and comparison sites (0.8%).
      Both rates are comparable with nationally reported levels (1.7% error rate for 50
      pharmacies).

PMID- 21896456
TI  - Influence of pharmacy practice on community pharmacists' integration of
      medication and lab value information from electronic health records.
AB  - OBJECTIVES: To describe how an electronic health record (EHR) was integrated into
      community pharmacists' patterns of patient care and to explore factors that are
      related to the use of medication and laboratory value information from the EHR.
      DESIGN: Descriptive, exploratory, nonexperimental study. SETTING: Edmonton,
      Canada, between November 2008 and March 2009. PARTICIPANTS: 16 pharmacists, 3
      pharmacy technicians, and 2 pharmacy interns from primary care networks, long
      term care settings, community independent and chain pharmacies, and grocery store
      pharmacies. INTERVENTION: Qualitative interviews. MAIN OUTCOME MEASURE:
      Pharmacists' self-reported use of EHR. RESULTS: Pharmacists in a patient-centered
      care practice (involving medication therapy management activities) were more
      likely to adopt the EHR for medication history and laboratory values, whereas
      pharmacists whose practice was focused on medication dispensing primarily used
      the EHR for patient demographic and dispensing records. Six general factors
      influenced the use of EHR: patients, pharmacists, pharmacy, other health
      professionals (i.e., physicians), EHR, and environment. Access to the medical
      record versus EHR and timeliness were barriers specific to pharmacists in a
      patient-centered practice. Factors that affected EHR use for pharmacists with
      primarily a dispensing practice were role understanding, dispensing versus lab
      records, valid reasons for using EHR, and fear of legal and disciplinary issues.
      CONCLUSION: Many community pharmacists embraced the EHR as a part of practice
      change, particularly those in patient-centered care practices. Practice type
      (patient-centered care or dispensing) greatly influenced pharmacists' use of EHR,
      specifically laboratory values. Because these qualitative findings are
      exploratory in nature, they may not be generalized beyond the participating
      pharmacies.

PMID- 21896457
TI  - Retrospective evaluation of an inpatient psychiatric pharmacist consultation
      service.
AB  - OBJECTIVE: To describe and evaluate clinical outcomes of pharmacist consult
      service recommendations in an inpatient psychiatric setting. DESIGN:
      Retrospective study. SETTING: Austin, TX, between September 1, 2005, and May 31,
      2006. PATIENTS: 105 patients receiving a pharmacy consult while admitted to the
      Austin State Hospital. INTERVENTION: Completion of consultation pursuant to
      provider referral. MAIN OUTCOME MEASURES: Clinical Global Impression (CGI)
      Severity (CGI-S) and CGI-Improvement (CGI-I) scores were retrospectively
      determined by blinded psychiatric pharmacy specialists upon review of physician
      progress notes. RESULTS: A total of 105 pharmacy consultations and associated
      physician progress notes were reviewed. Overall, 73% of the primary consultation
      recommendations were implemented. The most common reasons for referral to the
      psychopharmacology service were nonresponse to treatment and aggression. Patients
      with high implementation of consultation recommendations displayed more favorable
      endpoint CGI-S scores and displayed a greater CGI-I response rate compared with
      patients with low implementation of consult recommendations. CONCLUSION:
      Implementing clinical pharmacists' consult recommendations was associated with
      significantly greater improvement in overall severity of illness and global
      improvement. This study supports the positive role that pharmacists have in
      optimizing patient care and clinical outcomes.

PMID- 21896458
TI  - Treatment disparities for major depressive disorder: Implications for
      pharmacists.
AB  - OBJECTIVES: To determine whether differences exist in overall antidepressant use
      and specific antidepressant drug class (selective serotonin reuptake inhibitor
      [SSRI]/ serotonin norepinephrine reuptake inhibitor [SNRI] versus other) use
      among patients of different race/ethnicity groups (blacks and Hispanics compared
      with whites) with a diagnosis of Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition (DSM-IV) 12-month major depressive disorder (MDD) and
      to discuss ways in which pharmacists can decrease the gap in treatment
      disparities. DESIGN: Cross-sectional study. SETTING: United States from February
      2001 through April 2003. PARTICIPANTS: Respondents of the National Comorbidity
      Survey-Replication with DSM-IV 12-month MDD. INTERVENTION: Not applicable. MAIN
      OUTCOME MEASURES: Previous 12-month overall antidepressant use and previous 12
      month specific antidepressant drug class (SSRI/SNRI versus other) use. RESULTS:
      For respondents who screened positive for 12-month MDD (n = 362.3), only 34%
      reported antidepressant use in the previous 12-month period. Blacks (17.5%) and
      Hispanics (21.8%) reported significantly (P < 0.0001) lower overall use of
      antidepressants in the unadjusted analysis compared with whites (37.6%). Although
      not statistically significant, odds ratios (ORs) indicated that blacks and
      Hispanics were 61% and 47% less likely to report use of antidepressants (OR =
      0.39 [95% CI 0.20-0.77], P = 0.10, and 0.53 [0.31-0.91], P = 0.61, respectively).
      CONCLUSION: Among respondents with a diagnosis of MDD, race/ethnicity plays an
      important role in the use of antidepressants. The results of this study indicate
      a need for pharmacists to proactively interact and manage their patients'
      antidepressant therapy.

PMID- 21896459
TI  - Exploring the impact of an automated prescription-filling device on community
      pharmacy technician workflow.
AB  - OBJECTIVE: To explore community pharmacy technician workflow change after
      implementation of an automated robotic prescription-filling device. METHODS: At
      an independent community pharmacy in rural Mayville, WI, pharmacy technicians
      were observed before and 3 months after installation of an automated robotic
      prescription-filling device. The main outcome measures were sequences and timing
      of technician workflow steps, workflow interruptions, automation surprises, and
      workarounds. RESULTS: Of the 77 and 80 observations made before and 3 months
      after robot installation, respectively, 17 different workflow sequences were
      observed before installation and 38 after installation. Average prescription
      filling time was reduced by 40 seconds per prescription with use of the robot.
      Workflow interruptions per observation increased from 1.49 to 1.79 (P = 0.11),
      and workarounds increased from 10% to 36% after robot use. CONCLUSION: Although
      automated prescription-filling devices can increase efficiency, workflow
      interruptions and workarounds may negate that efficiency. Assessing changes in
      workflow and sequencing of tasks that may result from the use of automation can
      help uncover opportunities for workflow policy and procedure redesign.

PMID- 21896460
TI  - Pharmacists' actions when patients use complementary and alternative medicine
      with medications: A look at Texas-Mexico border cities.
AB  - OBJECTIVES: To determine how often pharmacists inquire about patients'
      complementary and alternative medicine (CAM) use, actions taken in response to
      patients' CAM use, and demographic or professional characteristics that predict
      differences in pharmacists' actions. METHODS: A survey was mailed to 400 randomly
      selected community pharmacists who resided in Texas-Mexico border cities.
      RESULTS: Most (63.8%) pharmacists had encountered patients who were using CAM.
      They documented CAM use in 9.8% of cases and monitored for drug-related problems
      in 39.4%. Among users, pharmacists sometimes to usually (3.4 +/- 1.4 [mean +/-
      SD]) took actions such as referring patients to their physicians. Pharmacists
      were not particularly comfortable (3.2 +/- 1.0) with responding to CAM inquiries
      but believed patients needed adequate CAM knowledge. Pharmacists rarely to
      sometimes (2.6 +/- 1.2) asked patients about their CAM use. Inquiry about CAM use
      was greater when information could be documented in profiles (F = 4.29, P = 0.02)
      and when pharmacists had additional training in CAM (t = -2.59, P = 0.01). Also,
      in pharmacies that stocked herbal or homeopathic products, pharmacists were more
      likely to recommend other CAM therapies appropriate for patients' conditions (t =
      -3.27, P < 0.01). CONCLUSION: Pharmacists were not very proactive in inquiring
      about CAM use, and their actions (e.g., referral to physician) were somewhat
      passive. More routine inquiry and documentation are needed. Pharmacists should
      routinely ask about and document CAM use by patients in order to optimize drug
      therapy outcomes.

PMID- 21896461
TI  - The Hispanic Diabetes Management Program: Impact of community pharmacists on
      clinical outcomes.
AB  - OBJECTIVE: To assess the impact of community pharmacists on clinical outcomes in
      Hispanic patients with type 2 diabetes. METHODS: 126 patients were enrolled in
      this longitudinal pre/post cohort study that took place in nine community and
      four workplace pharmacies in San Antonio, TX. Pharmacists provided education,
      point-of-care testing for glycemic and metabolic parameters, clinical assessment,
      goal setting, and drug therapy management with physicians. Study outcomes were
      changes in glycosylated hemoglobin (A1C) and accompanying metabolic parameters
      (blood pressure, lipid parameters, and body mass index) during a 1-year time
      frame. RESULTS: In the overall cohort, A1C was not reduced significantly from
      baseline to 12 months (7.8% vs. 7.6%, P = 0.516). However, statistically
      significant reductions occurred for fasting plasma glucose, triglycerides, and
      diastolic blood pressure. None of the other parameters was affected
      significantly. In the subgroup of patients not at target values at baseline,
      significant reductions occurred for A1C (9.2% vs. 8.6%, P = 0.001), systolic
      blood pressure (147 vs. 143 mm Hg, P = 0.031), diastolic blood pressure (91 vs.
      87 mm Hg, P < 0.001), triglycerides (259 vs. 219 mg/dL, P < 0.001), LDL
      cholesterol (139 vs. 123 mg/dL, P < 0.001), and total cholesterol (237 vs. 222
      mg/dL, P = 0.008). CONCLUSION: Interventions performed by community pharmacists
      are effective in improving clinical outcomes in a Hispanic cohort with diabetes.
      Pharmacists' efforts were most successful in patients not at target glycemic and
      metabolic levels.

PMID- 21896462
TI  - Role of student pharmacists in the identification and prevention of medication
      related problems.
AB  - OBJECTIVES: To measure the total rate of attending physician, medical resident,
      and medical student acceptance of interventions recommended by third-year student
      pharmacists supervised by a licensed pharmacist and to determine the type of
      health care provider group that accepted the most interventions, type of
      interventions provided, and number of patients counseled on medication use.
      METHODS: This prospective unblinded pilot study followed single interventions
      documented by nine third-year student pharmacists enrolled at the University of
      Louisiana at Monroe College of Pharmacy. Success rates of suggested interventions
      made to family medicine attending physicians, pharmacists, medical residents, and
      medical students in three Louisiana outpatient clinics were documented. Student
      pharmacists performed medication histories, identified potential medication
      related problems, discussed interventions with health care providers, and
      counseled patients on medication use. Outcomes assessed were intervention type
      and number, intervention acceptance rate, and number of patients counseled.
      RESULTS: Student pharmacists communicated with attending physicians, medical
      residents, and/or medical students regarding 32 patients. A total of 48
      interventions were documented. Of these interventions, 34 were potential
      medication-related problems, 8 were pharmacotherapeutic recommendations for a new
      problem, 4 were responses to a health care provider's drug information requests,
      and 2 were referrals to a diabetes education class. The acceptance rate of
      student pharmacists' recommendations was 86%. Attending physicians accepted 93.8%
      of recommended interventions, medical residents 70%, and medical students 87.5%,
      Student pharmacists counseled 29 patients on medication use. CONCLUSION: Student
      pharmacists were able to recommend new drug regimens and discuss changes in
      therapy with health care providers. Attending physicians, medical residents, and
      medical students accepted the majority of students' recommendations. Third-year
      student pharmacists have the potential to serve an important role in the
      identification and prevention of medication-related problems by suggesting
      interventions to health care providers.

PMID- 21896463
TI  - Evaluation of the pharmaceutical case management program implemented in a private
      sector health plan.
AB  - OBJECTIVES: To characterize the drug-related problems (DRPs) identified by
      pharmacists providing pharmaceutical case management (PCM), describe the effect
      of PCM on medication appropriateness, and compare the findings from this
      evaluation of private insurance beneficiaries with a previous evaluation of PCM
      provided to Iowa Medicaid beneficiaries. METHODS: A pharmacy chart review was
      used to calculate medication appropriateness index (MAI) scores for patients
      before and after receiving PCM. Changes in MAI scores were calculated. DRPs
      identified by pharmacists during PCM services were characterized using online
      summaries submitted by pharmacists following each PCM encounter. RESULTS: A total
      of 91 patients received 195 PCM services from 29 pharmacies (2.14
      services/patient). On average, pharmacists providing PCM were able to identify
      2.6 DRPs per patient. The most frequently identified problems were the need for
      additional therapy, adverse drug reactions, and inappropriate adherence. Compared
      with baseline, mean MAI scores did not improve significantly following PCM (1.53
      vs. 1.24, P = 0.34). MAI scores for this group were significantly lower than in a
      previous study of Medicaid beneficiaries receiving PCM. CONCLUSION: The lower
      number of medications and lower MAI scores for the private beneficiaries compared
      with Medicaid beneficiaries suggested that these two groups have different
      characteristics that could translate into different needs from medication therapy
      management services.

PMID- 21896464
TI  - Joint Forces Pharmacy Seminar 2011 abstracts of contributed papers.

PMID- 21896465
TI  - Journal of the American Pharmaceutical Association (1940-1960).

PMID- 21896466
TI  - Maternal influenza vaccination: Protecting two lives with one vaccine.

PMID- 21896467
TI  - Roflumilast, indacaterol maleate, and abiraterone acetate.

PMID- 21896468
TI  - Standalone or managed care drug plans, postarthroplasty thromboprophylaxis, and
      risperidone for PTSD.

PMID- 21896469
TI  - Personalized medicine: genetic component to providing quality care.
AB  - Personalized medicine--tailoring medical treatment not only to patients'
      individual characteristics, but also to their genetic profiles--is a new trend
      that is gaining attention in health care. It has the potential to manage diseases
      with a minimum of side effects and adverse reactions while, at the same time, cut
      unnecessary costs. Creating genetic profiles can determine if a patient has a
      predisposition to specific diseases and what treatments are likely to be most
      effective for a particular illness. Pharmacists can play a key role in
      personalized medicine by working with prescribers to take medication management
      to a new level of effectiveness and accuracy. Personalized medicine is in its
      infancy, and while studies are beginning to show its impact, it isn't likely to
      be used on a widespread basis until it becomes more affordable, available, and
      integrated in health care payment. However, as the health care system continues
      to evolve, providers and payers alike are expected to embrace personalized
      medicine. And even though technological innovations are slow to come to long-term
      care, personalized medicine is likely to become more widely used in this setting
      as the advantages become evident.

PMID- 21896470
TI  - Understanding frailty in the geriatric population.
AB  - Clinicians who work with the frail elderly know what frailty looks like, but
      until recently, they have had no science-based definition of this condition.
      Frailty is classified as a medical syndrome, and Fried et al. were among the
      first to standardize the definition of frailty as a distinct syndrome with
      biologic underpinnings. Their definition describes a clinical phenotype of
      decreased reserve and resistance to stressors, with clinical manifestations of a
      mutually exacerbating cycle of negative energy balance, sarcopenia, diminished
      strength, and exertion intolerance. Age is no longer considered a defining
      characteristic, although frailty is still considered primarily a geriatric
      problem. Approximately two-thirds of affected individuals enter frailty in a
      slow, progressive way, while one-third become frail cataclysmically. Weakness is
      a common early sign, and exhaustion and weight loss are often late
      manifestations. Observing early behavioral changes before frailty develops could
      provide insight into its development and suggest early interventions. Since
      frailty is clearly associated with adverse outcomes, a healthy, active lifestyle
      is the cornerstone of prevention, and many researchers suggest that resistance
      training can reverse some muscle loss and improve functioning. When the health
      care team proposes any change in care, including a new medication, it should be
      prepared to describe how the intervention may affect cognition, memory, energy,
      or function.

PMID- 21896471
TI  - Measurement of unused medication in Medicare Part D residents in skilled nursing
      facilities.
AB  - OBJECTIVE: To determine the cost of unused medication dispensed to Medicare Part
      D residents in nursing facilities in the United States and to describe the
      distribution of unused medication based on dispensed prescription cost and unit
      medication cost. DESIGN: A prospective study in which dispensed and returned
      prescription data for Medicare Part D residents encompassing the first six months
      of 2010 were provided by eight long-term care pharmacies servicing approximately
      33,700 residents in 425 facilities. SETTING: Nursing facilities. PATIENTS:
      Residents covered by Medicare Part D. MAIN OUTCOME MEASURES: Unused medication as
      a percentage of dispensed prescriptions was calculated based on the number of
      returned prescriptions and the cost of unused medication for all dosage forms and
      for solid oral forms. RESULTS: For all dosage forms, 6.8% of dispensed
      prescriptions were returned partially used, representing 3.5% of dispensed cost.
      For solid oral dosage forms, 6.1% of all dispensed prescriptions were returned
      partially used, representing 2.9% +/- 1% of total dispensed cost. For returned
      oral solid prescriptions, 24% had a dispensed cost of $50 or more but accounted
      for 84% of the cost of returned medications; 26% had a unit cost of $1 of more,
      but accounted for 83% of the cost. The total amount of unconsumed solid oral
      medication for Medicare Part D residents in skilled nursing facilities was
      estimated at $125 million annually. CONCLUSION: The estimated cost of unconsumed
      medications dispensed to Medicare Part D residents in nursing facilities is
      approximately 3% of dispensed cost, amounting to approximately $125 million
      across all U.S. nursing facilities.

PMID- 21896472
TI  - Hypothyroidism and subclinical hypothyroidism in the older patient.
AB  - OBJECTIVE: To review the etiology, precipitating factors, clinical findings,
      screening recommendations, and treatment for primary hypothyroidism and
      subclinical hypothyroidism in the older patient. DATA SOURCES: A PubMed search of
      English language articles using a combination of words: elderly, thyroid,
      hypothyroid,* subclinical hypothyroid,* etiology, screening, diagnosis, and
      treatment to identify original studies, guidelines, and reviews on primary
      hypothyroidism and subclinical hypothyroidism published between 1979 and present.
      STUDY SELECTION AND DATA EXTRACTION: Overall, 51 clinical reviews, original
      studies, references, and guidelines were obtained and evaluated on their clinical
      relevance to the older patient population. DATA SYNTHESIS: The literature
      included guidelines and considerations for the diagnosis, screening, and
      management of subclinical and overt primary hypothyroidism in the older patient.
      CONCLUSION: Females and individuals 60 years of age or older have a higher
      prevalence of primary hypothyroidism and subclinical hypothyroidism. While
      screening recommendations exist, the need or suggested age to initiate screening
      varies among organizations. TSH and free T4 values are used for diagnosing and
      monitoring. Levothyroxine remains the drug of choice for replacing endogenous
      thyroid hormone. Despite evidence to suggest its need, the treatment of
      subclinical hypothyroidism remains controversial.

PMID- 21896473
TI  - Progressive tremor, truncal ataxia, and acute mental status changes after use of
      bupropion.
AB  - An 84-year-old male with stage III chronic kidney disease and a history of
      multiple psychiatric and medical disorders presented to the emergency department
      (ED) with new onset proximal leg weakness with tremor upon standing, truncal
      ataxia, and myoclonic jerks of the upper extremity that had progressively
      worsened over three weeks. Magnetic resonance imaging and head computed
      tomography showed no acute change from baseline. After admission, the patient
      reported visual hallucinations, vertigo, and slurred speech, and displayed
      nocturnal agitation/delirium. These symptoms were managed with risperidone. Prior
      to admission, the most recent medication change was the initiation of bupropion
      100 mg extended-release twice daily. Bupropion was titrated to 150 mg twice daily
      over the three weeks prior to the ED visit. Gradual tapering of the bupropion
      dose was started after admission. Symptoms of agitation, delirium, speech, and
      motor disturbances decreased 36 to 48 hours after bupropion dose was lowered to
      75 mg daily, and risperidone was changed to quetiapine. The patient was
      discharged to short-term rehabilitation with return of mental status to baseline.
      Bupropion and quetiapine were discontinued at discharge from the rehabilitation
      center. Case reports exist for acute psychotic and parkinsonian symptoms after
      administration of bupropion and bupropion extended-release, but none exist for
      the combination of focal neurologic deficits and psychotic symptoms found in this
      patient's presentation. Limited pharmacokinetic data in the elderly and those
      with renal impairment suggest that this patient population may have reduced
      clearance of bupropion. Dose adjustment should be considered in such patients and
      signs of toxicity closely monitored. Adverse reactions to bupropion should be
      considered if a patient presents with acute neurologic or psychotic symptoms
      after initiation or dose modification of bupropion.

PMID- 21896474
TI  - Dealing with those difficult coworkers.

PMID- 21896476
TI  - WITHDRAWN: Ceramide kinase regulates the production of TNF{alpha} via inhibition
      of TNF{alpha}-converting enzyme.
AB  - This manuscript was withdrawn by the author.

PMID- 21896475
TI  - Modification of histones by sugar beta-N-acetylglucosamine (GlcNAc) occurs on
      multiple residues, including histone H3 serine 10, and is cell cycle-regulated.
AB  - The monosaccharide, beta-N-acetylglucosamine (GlcNAc), can be added to the
      hydroxyl group of either serines or threonines to generate an O-linked beta-N
      acetylglucosamine (O-GlcNAc) residue (Love, D. C., and Hanover, J. A. (2005) Sci.
      STKE 2005 312, 1-14; Hart, G. W., Housley, M. P., and Slawson, C. (2007) Nature
      446, 1017-1022). This post-translational protein modification, termed O
      GlcNAcylation, is reversible, analogous to phosphorylation, and has been
      implicated in many cellular processes. Here, we present evidence that in human
      cells all four core histones of the nucleosome are substrates for this
      glycosylation in the relative abundance H3, H4/H2B, and H2A. Increasing the
      intracellular level of UDP-GlcNAc, the nucleotide sugar donor substrate for O
      GlcNAcylation enhanced histone O-GlcNAcylation and partially suppressed
      phosphorylation of histone H3 at serine 10 (H3S10ph). Expression of recombinant
      H3.3 harboring an S10A mutation abrogated histone H3 O-GlcNAcylation relative to
      its wild-type version, consistent with H3S10 being a site of histone O
      GlcNAcylation (H3S10glc). Moreover, O-GlcNAcylated histones were lost from
      H3S10ph immunoprecipitates, whereas immunoprecipitation of either H3K4me3 or
      H3K9me3 (active or inactive histone marks, respectively) resulted in co
      immunoprecipitation of O-GlcNAcylated histones. We also examined histone O
      GlcNAcylation during cell cycle progression. Histone O-GlcNAcylation is high in
      G(1) cells, declines throughout the S phase, increases again during late S/early
      G(2), and persists through late G(2) and mitosis. Thus, O-GlcNAcylation is a
      novel histone post-translational modification regulating chromatin conformation
      during transcription and cell cycle progression.

PMID- 21896477
TI  - Exosite interactions impact matrix metalloproteinase collagen specificities.
AB  - Members of the matrix metalloproteinase (MMP) family selectively cleave collagens
      in vivo. However, the substrate structural determinants that facilitate
      interaction with specific MMPs are not well defined. We hypothesized that type I
      III collagen sequences located N- or C-terminal to the physiological cleavage
      site mediate substrate selectivity among MMP-1, MMP-2, MMP-8, MMP-13, and MMP
      14/membrane-type 1 (MT1)-MMP. The enzyme kinetics for hydrolysis of three
      fluorogenic triple-helical peptides (fTHPs) was evaluated herein. The first fTHP
      contained consensus residues 769-783 from type I-III collagens, the second
      inserted alpha1(II) collagen residues 763-768 N-terminal to the consensus
      sequence, and the third inserted alpha1(II) collagen residues 784-792 C-terminal
      to the consensus sequence. Our analyses showed that insertion of the C-terminal
      residues significantly increased k(cat)/K(m) and k(cat) for MMP-1. MMP-13 showed
      the opposite behavior with a decreased k(cat)/K(m) and k(cat) and a greatly
      improved K(m) in response to the C-terminal residues. Insertion of the N-terminal
      residues enhanced k(cat)/K(m) and k(cat) for MMP-8 and MT1-MMP. For MMP-2, the C
      terminal residues enhanced K(m) and dramatically decreased k(cat), resulting in a
      decrease in the overall activity. These changes in activities and kinetic
      parameters represented the collagen preferences of MMP-8, MMP-13, and MT1-MMP
      well. Thus, interactions with secondary binding sites (exosites) helped direct
      the specificity of these enzymes. However, MMP-1 collagen preferences were not
      recapitulated by the fTHP studies. The preference of MMP-1 for type III collagen
      appears to be primarily based on the flexibility of the hydrolysis site of type
      III collagen compared with types I and II. Further characterization of exosite
      determinants that govern interactions of MMPs with collagenous substrates should
      aid the development of pharmacotherapeutics that target individual MMPs.

PMID- 21896478
TI  - The E3 ubiquitin ligase mind bomb-2 (MIB2) protein controls B-cell CLL/lymphoma
      10 (BCL10)-dependent NF-kappaB activation.
AB  - B-cell CLL/lymphoma 10 (BCL10) is crucial for the activation of NF-kappaB in
      numerous immune receptor signaling pathways, including the T-cell receptor (TCR)
      and B-cell receptor signaling pathways. However, the molecular mechanisms that
      lead to signal transduction from BCL10 to downstream NF-kappaB effector kinases,
      such as TAK1 and components of the IKK complex, are not entirely understood. Here
      we used a proteomic approach and identified the E3 ligase MIB2 as a novel
      component of the activated BCL10 complex. In vitro translation and pulldown
      assays suggest direct interaction between BCL10 and MIB2. Overexpression
      experiments show that MIB2 controls BCL10-mediated activation of NF-kappaB by
      promoting autoubiquitination and ubiquitination of IKKgamma/NEMO, as well as
      recruitment and activation of TAK1. Knockdown of MIB2 inhibited BCL10-dependent
      NF-kappaB activation. Together, our results identify MIB2 as a novel component of
      the activated BCL10 signaling complex and a missing link in the BCL10-dependent
      NF-kappaB signaling pathway.

PMID- 21896479
TI  - Cysteine cathepsins S and L modulate anti-angiogenic activities of human
      endostatin.
AB  - Human endostatin, a potent anti-angiogenic protein, is generated by release of
      the C terminus of collagen XVIII. Here, we propose that cysteine cathepsins are
      involved in both the liberation and activation of bioactive endostatin fragments,
      thus regulating their anti-angiogenic properties. Cathepsins B, S, and L
      efficiently cleaved in vitro FRET peptides that encompass the hinge region
      corresponding to the N terminus of endostatin. However, in human umbilical vein
      endothelial cell-based assays, silencing of cathepsins S and L, but not cathepsin
      B, impaired the generation of the ~22-kDa endostatin species. Moreover,
      cathepsins L and S released two peptides from endostatin with increased
      angiostatic properties and both encompassing the NGR sequence, a vasculature
      homing motif. The G10T peptide (residues 1455-1464: collagen XVIII numbering)
      displayed compelling anti-proliferative (EC(50) = 0.23 nm) and proapoptotic
      properties. G10T inhibited aminopeptidase N (APN/CD13) and reduced tube formation
      of endothelial cells in a manner similar to bestatin. Combination of G10T with
      bestatin resulted in no further increase in anti-angiogenic activity. Taken
      together, these data suggest that endostatin-derived peptides may represent novel
      molecular links between cathepsins and APN/CD13 in the regulation of
      angiogenesis.

PMID- 21896480
TI  - Asp- and Glu-specific novel dipeptidyl peptidase 11 of Porphyromonas gingivalis
      ensures utilization of proteinaceous energy sources.
AB  - Porphyromonas gingivalis and Porphyromonas endodontalis, asaccharolytic black
      pigmented anaerobes, are predominant pathogens of human chronic and periapical
      periodontitis, respectively. They incorporate di- and tripeptides from the
      environment as carbon and energy sources. In the present study we cloned a novel
      dipeptidyl peptidase (DPP) gene of P. endodontalis ATCC 35406, designated as
      DPP11. The DPP11 gene encoded 717 amino acids with a molecular mass of 81,090 Da
      and was present as a 75-kDa form with an N terminus of Asp(22). A homology search
      revealed the presence of a P. gingivalis orthologue, PGN0607, that has been
      categorized as an isoform of authentic DPP7. P. gingivalis DPP11 was exclusively
      cell-associated as a truncated 60-kDa form, and the gene ablation retarded cell
      growth. DPP11 specifically removed dipeptides from oligopeptides with the
      penultimate N-terminal Asp and Glu and has a P2-position preference to
      hydrophobic residues. Optimum pH was 7.0, and the k(cat)/K(m) value was higher
      for Asp than Glu. Those activities were lost by substitution of Ser(652) in P.
      endodontalis and Ser(655) in P. gingivalis DPP11 to Ala, and they were
      consistently decreased with increasing NaCl concentration. Arg(670) is a unique
      amino acid completely conserved in all DPP11 members distributed in the genera
      Porphyromonas, Bacteroides, and Parabacteroides, whereas this residue is
      converted to Gly in all authentic DPP7 members. Substitution analysis suggested
      that Arg(670) interacts with an acidic residue of the substrate. Considered to
      preferentially utilize acidic amino acids, DPP11 ensures efficient degradation of
      oligopeptide substrates in these Gram-negative anaerobic rods.

PMID- 21896481
TI  - The general definition of the p97/valosin-containing protein (VCP)-interacting
      motif (VIM) delineates a new family of p97 cofactors.
AB  - Cellular functions of the essential, ubiquitin-selective AAA ATPase p97/valosin
      containing protein (VCP) are controlled by regulatory cofactors determining
      substrate specificity and fate. Most cofactors bind p97 through a ubiquitin
      regulatory X (UBX) or UBX-like domain or linear sequence motifs, including the
      hitherto ill defined p97/VCP-interacting motif (VIM). Here, we present the new,
      minimal consensus sequence RX(5)AAX(2)R as a general definition of the VIM that
      unites a novel family of known and putative p97 cofactors, among them UBXD1 and
      ZNF744/ANKZF1. We demonstrate that this minimal VIM consensus sequence is
      necessary and sufficient for p97 binding. Using NMR chemical shift mapping, we
      identified several residues of the p97 N-terminal domain (N domain) that are
      critical for VIM binding. Importantly, we show that cellular stress resistance
      conferred by the yeast VIM-containing cofactor Vms1 depends on the physical
      interaction between its VIM and the critical N domain residues of the yeast p97
      homolog, Cdc48. Thus, the VIM-N domain interaction characterized in this study is
      required for the physiological function of Vms1 and most likely other members of
      the newly defined VIM family of cofactors.

PMID- 21896482
TI  - A unique role for heat shock protein 70 and its binding partner tissue
      transglutaminase in cancer cell migration.
AB  - Cell migration is essential for several important biological outcomes and is
      involved in various developmental disorders and disease states including cancer
      cell invasiveness and metastasis. A fundamental step in cell migration is the
      development of a leading edge. By using HeLa carcinoma cells as an initial model
      system, we uncovered a surprising role for the heat shock protein 70 (Hsp70) and
      its ability to bind the protein cross-linking enzyme, tissue transglutaminase
      (tTG), in cancer cell migration. Treatment of HeLa cells with EGF results in the
      activation of a plasma membrane-associated pool of tTG and its redistribution to
      the leading edges of these cells, which are essential events for EGF-stimulated
      HeLa cell migration. However, we then found that the ability of tTG to be
      localized to the leading edge is dependent on Hsp70. Similarly, the localization
      of tTG to the leading edges of MDAMB231 breast carcinoma cells, where it also
      plays an essential role in their migration, has a strict requirement for Hsp70.
      Treatment of these different cell lines with inhibitors against the ATP
      hydrolytic activity of Hsp70 prevented tTG from localizing to their leading edges
      and thereby blocked EGF-stimulated HeLa cell migration, as well as the
      constitutive migration normally exhibited by MDAMB231 cells. These findings
      highlight a new and unconventional role for the chaperonin activity of Hsp70 in
      the localization of a key regulatory protein (tTG) at the leading edges of cancer
      cells and the important consequences that this holds for their ability to
      migrate.

PMID- 21896483
TI  - Local elongation of endothelial cell-anchored von Willebrand factor strings
      precedes ADAMTS13 protein-mediated proteolysis.
AB  - Platelet-decorated von Willebrand factor (VWF) strings anchored to the
      endothelial surface are rapidly cleaved by ADAMTS13. Individual VWF string
      characteristics such as number, location, and auxiliary features of the ADAMTS13
      cleavage sites were explored here using imaging and computing software. By
      following changes in VWF string length, we demonstrated that VWF strings are
      cleaved multiple times, successively shortening string length in the function of
      time and generating fragments ranging in size from 5 to over 100 MUm. These are
      larger than generally observed in normal plasma, indicating that further
      proteolysis takes place in circulation. Interestingly, in 89% of all cleavage
      events, VWF strings elongate precisely at the cleavage site before ADAMTS13
      proteolysis. These local elongations are a general characteristic of VWF strings,
      independent of the presence of ADAMTS13. Furthermore, large elongations, ranging
      in size from 1.4 to 40 MUm, occur at different sites in space and time. In
      conclusion, ADAMTS13-mediated proteolysis of VWF strings under flow is preceded
      by large elongations of the string at the cleavage site. These elongations may
      lead to the simultaneous exposure of many exosites, thereby facilitating ADAMTS13
      mediated cleavage.

PMID- 21896484
TI  - The vitamin K-dependent carboxylase generates gamma-carboxylated glutamates by
      using CO2 to facilitate glutamate deprotonation in a concerted mechanism that
      drives catalysis.
AB  - The gamma-glutamyl carboxylase converts Glu to carboxylated Glu (Gla) to activate
      a large number of vitamin K-dependent proteins with diverse functions, and this
      broad physiological impact makes it critical to understand the mechanism of
      carboxylation. Gla formation is thought to occur in two independent steps (i.e.
      Glu deprotonation to form a carbanion that then reacts with CO(2)), based on
      previous studies showing unresponsiveness of Glu deprotonation to CO(2). However,
      our recent studies on the kinetic properties of a variant enzyme (H160A) showing
      impaired Glu deprotonation prompted a reevaluation of this model. Glu
      deprotonation monitored by tritium release from the glutamyl gamma-carbon was
      dependent upon CO(2), and a proportional increase in both tritium release and Gla
      formation occurred over a range of CO(2) concentrations. This discrepancy with
      the earlier studies using microsomes is probably due to the known accessibility
      of microsomal carboxylase to water, which reprotonates the carbanion. In
      contrast, tritium incorporation experiments with purified carboxylase showed very
      little carbanion reprotonation and consequently revealed the dependence of Glu
      deprotonation on CO(2). Cyanide stimulated Glu deprotonation and carbanion
      reprotonation to the same extent in wild type enzyme but not in the H160A
      variant. Glu deprotonation that depends upon CO(2) but that also occurs when
      water or cyanide are present strongly suggests a concerted mechanism facilitated
      by His-160 in which an electrophile accepts the negative charge on the developing
      carbanion. This revised mechanism provides important insight into how the
      carboxylase catalyzes the reaction by avoiding the formation of a high energy
      discrete carbanion.

PMID- 21896485
TI  - Activation of BlaR1 protein of methicillin-resistant Staphylococcus aureus, its
      proteolytic processing, and recovery from induction of resistance.
AB  - The fates of BlaI, the gene repressor protein for the bla operon, BlaR1, the beta
      lactam sensor/signal transducer, and PC1 beta-lactamase in four strains of
      Staphylococcus aureus upon exposure to four different beta-lactam antibiotics
      were investigated as a function of time. The genes for the three proteins are
      encoded by the bla operon, the functions of which afford inducible resistance to
      beta-lactam antibiotics in S. aureus. BlaR1 protein is expressed at low copy
      number. Acylation of the sensor domain of BlaR1 by beta-lactam antibiotics
      initiates signal transduction to the cytoplasmic domain, a zinc protease, which
      is activated and degrades BlaI. This proteolytic degradation derepresses
      transcription of all three genes, resulting in inducible resistance. These
      processes take place within minutes of exposure to the antibiotics. The BlaR1
      protein was shown to undergo fragmentation in three S. aureus strains within the
      time frame relevant for manifestation of resistance and was below the detection
      threshold in the fourth. Two specific sites of fragmentation were identified, one
      cytoplasmic and the other in the sensor domain. This is proposed as a means for
      turnover, a process required for recovery from induction of resistance in S.
      aureus in the absence of the antibiotic challenge. In S. aureus not exposed to
      beta-lactam antibiotics (i.e. not acylated by antibiotic) the same fragmentation
      of BlaR1 is still observed, including the shedding of the sensor domain, an
      observation that leads to the conclusion that the sites of proteolysis might have
      evolved to predispose the protein to degradation within a set period of time.

PMID- 21896486
TI  - Novel gamma-secretase enzyme modulators directly target presenilin protein.
AB  - gamma-Secretase is essential for the generation of the neurotoxic 42-amino acid
      amyloid beta-peptide (Abeta(42)). The aggregation-prone hydrophobic peptide,
      which is deposited in Alzheimer disease (AD) patient brain, is generated from a C
      terminal fragment of the beta-amyloid precursor protein by an intramembrane
      cleavage of gamma-secretase. Because Abeta(42) is widely believed to trigger AD
      pathogenesis, gamma-secretase is a key AD drug target. Unlike inhibitors of the
      enzyme, gamma-secretase modulators (GSMs) selectively lower Abeta(42) without
      interfering with the physiological function of gamma-secretase. The molecular
      target(s) of GSMs and hence the mechanism of GSM action are not established. Here
      we demonstrate by using a biotinylated photocross-linkable derivative of highly
      potent novel second generation GSMs that gamma-secretase is a direct target of
      GSMs. The GSM photoprobe specifically bound to the N-terminal fragment of
      presenilin, the catalytic subunit of gamma-secretase, but not to other gamma
      secretase subunits. Binding was differentially competed by GSMs of diverse
      structural classes, indicating the existence of overlapping/multiple GSM binding
      sites or allosteric alteration of the photoprobe binding site. The beta-amyloid
      precursor protein C-terminal fragment previously implicated as the GSM binding
      site was not targeted by the compound. The identification of presenilin as the
      molecular target of GSMs directly establishes allosteric modulation of enzyme
      activity as a mechanism of GSM action and may contribute to the development of
      therapeutically active GSMs for the treatment of AD.

PMID- 21896487
TI  - The large extracellular loop of organic cation transporter 1 influences substrate
      affinity and is pivotal for oligomerization.
AB  - Polyspecific organic anion transporters (OATs) and organic cation transporters
      (OCTs) of the SLC22 transporter family play a pivotal role in absorption,
      distribution, and excretion of drugs. Polymorphisms in these transporters
      influence therapeutic effects. On the basis of functional characterizations,
      homology modeling, and mutagenesis, hypotheses for how OCTs bind and translocate
      structurally different cations were raised, assuming functionally competent
      monomers. However, homo-oligomerization has been described for OATs and OCTs. In
      the present study, evidence is provided that the large extracellular loops (EL)
      of rat Oct1 (rOct1) and rat Oat1 (rOat1) mediate homo- but not hetero
      oligomerization. Replacement of the cysteine residues in the EL of rOct1 by
      serine residues (rOct1(6DeltaC-l)) or breaking disulfide bonds with
      dithiothreitol prevented oligomerization. rOct1 chimera containing the EL of
      rOat1 (rOct1(rOat1-l)) showed oligomerization but reduced transporter amount in
      the plasma membrane. For rOct1(6DeltaC-l) and rOct1(rOat1-l), similar K(m) values
      for 1-methyl-4-phenylpyridinium(+) (MPP(+)) and tetraethylammonium(+) (TEA(+))
      were obtained that were higher compared with rOct1 wild type. The increased K(m)
      of rOct1(rOat1-l) indicates an allosteric effect of EL on the cation binding
      region. The similar substrate affinity of the oligomerizing and non-oligomerizing
      loop mutants suggests that oligomerization does not influence transport function.
      Independent transport function of rOct1 monomers was also demonstrated by showing
      that K(m) values for MPP(+) and TEA(+) were not changed after treatment with
      dithiothreitol and that a tandem protein with two rOct1 monomers showed about 50%
      activity with unchanged K(m) values for MPP(+) and TEA(+) when one monomer was
      blocked. The data help to understand how OCTs work and how mutations in patients
      may affect their functions.

PMID- 21896488
TI  - Glioma-derived T cell immunoglobulin- and mucin domain-containing molecule-4
      (TIM4) contributes to tumor tolerance.
AB  - Tumor tolerance plays a critical role in tumor growth and escape from immune
      surveillance. The mechanism of tumor tolerance development is not fully
      understood. Regulatory T cells (Tregs) play a critical role in tumor tolerance.
      TIM4 (T cell immunoglobulin- and mucin domain-containing molecule-4) is involved
      in immune regulation. We investigated the role of TIM4 in the induction of Tregs
      in tumors. Surgically removed glioma tissue and peripheral blood samples were
      obtained from 25 glioma patients. Immune cells were isolated from the tissue and
      blood samples. Confocal microscopy was employed to detect macrophages
      phagocytosing apoptotic T cells. The generation of tumor-specific Tregs and the
      immune suppression function of Tregs were observed in cell culture models. High
      levels of TIM4 were detected in glioma-derived macrophages. Phosphatidylserine
      (PS) was detected in glioma-derived T cells; naive T cells expressed low levels
      of PS that could be up-regulated by hypoxia. Glioma-derived macrophages
      phagocytosed PS-expressing T cells, gaining the tolerogenic properties, which
      could induce tumor-specific Tregs; the latter could suppress tumor-specific
      CD8(+) T cells. We conclude that macrophage-derived TIM4 plays an important role
      in the induction of Tregs in gliomas, which may play an important role in tumor
      tolerance.

PMID- 21896489
TI  - Apolipoprotein A-I exerts bactericidal activity against Yersinia enterocolitica
      serotype O:3.
AB  - Apolipoprotein A-I (apoA-I), the main protein component of high density
      lipoprotein (HDL), is well recognized for its antiatherogenic, antioxidant, and
      antiinflammatory properties. Here, we report a novel role for apoA-I as a host
      defense molecule that contributes to the complement-mediated killing of an
      important gastrointestinal pathogen, Gram-negative bacterium Yersinia
      enterocolitica. We specifically show that the C-terminal domain of apoA-I is the
      effector site providing the bactericidal activity. Although the presence of the
      lipopolysaccharide O-antigen on the bacterial surface is absolutely required for
      apoA-I to kill the bacteria, apoA-I does not interact with the bacteria directly.
      To the contrary, exposure of the bacteria by serum proteins triggers apoA-I
      deposition on the bacterial surface. As our data show that both purified lipid
      free and HDL-associated apoA-I displays anti-bacterial potential, apoA-I mimetic
      peptides may be a promising therapeutic agent for the treatment of certain Gram
      negative infections.

PMID- 21896490
TI  - Ubiquitin-mediated regulation of CD86 protein expression by the ubiquitin ligase
      membrane-associated RING-CH-1 (MARCH1).
AB  - The activation of naive T cells requires antigen presentation by dendritic cells
      (DCs), and the process of antigen presentation is regulated over the course of DC
      maturation. One key aspect of this regulation is the cell surface up-regulation
      upon DC maturation of peptide.MHC-II complexes and the costimulatory molecule
      CD86. It is now clear that these critical induction events involve changes in
      ubiquitin-dependent trafficking of MHC-II and CD86 by the E3 ligase membrane
      associated RING-CH-1 (MARCH1). Although ubiquitin-dependent trafficking of MHC-II
      has been well characterized, much less is known regarding the post
      transcriptional regulation of CD86 expression. Here, we examined the physical and
      functional interaction between CD86 and MARCH1. We observed that CD86 is rapidly
      endocytosed in the presence of MARCH1 followed by lysosome-dependent degradation.
      Furthermore, we found that the association between CD86 and MARCH1 was conferred
      primarily by the transmembrane domains of the respective proteins. In contrast to
      MHC-II, which has a single, conserved ubiquitin acceptor site in the cytosolic
      domain, we found that multiple lysine residues in the cytosolic tail of CD86
      could support ubiquitination consistent with the relative lack of sequence
      conservation across species within the CD86 cytosolic domain. These findings
      suggest that MARCH1 recruits multiple substrates via transmembrane domain
      mediated interactions to permit substrate ubiquitination in the face of diverse
      cytosolic domain sequences.

PMID- 21896491
TI  - Genomic analysis reveals a novel nuclear factor-kappaB (NF-kappaB)-binding site
      in Alu-repetitive elements.
AB  - The transcription factor NF-kappaB is a critical regulator of immune responses.
      To determine how NF-kappaB builds transcriptional control networks, we need to
      obtain a topographic map of the factor bound to the genome and correlate it with
      global gene expression. We used a ChIP cloning technique and identified novel NF
      kappaB target genes in response to virus infection. We discovered that most of
      the NF-kappaB-bound genomic sites deviate from the consensus and are located away
      from conventional promoter regions. Remarkably, we identified a novel abundant NF
      kappaB-binding site residing in specialized Alu-repetitive elements having the
      potential for long range transcription regulation, thus suggesting that in
      addition to its known role, NF-kappaB has a primate-specific function and a role
      in human evolution. By combining these data with global gene expression profiling
      of virus-infected cells, we found that most of the sites bound by NF-kappaB in
      the human genome do not correlate with changes in gene expression of the nearby
      genes and they do not appear to function in the context of synthetic promoters.
      These results demonstrate that repetitive elements interspersed in the human
      genome function as common target sites for transcription factors and may play an
      important role in expanding the repertoire of binding sites to engage new genes
      into regulatory networks.

PMID- 21896492
TI  - The endosomal Na(+)/H(+) exchanger contributes to multivesicular body formation
      by regulating the recruitment of ESCRT-0 Vps27p to the endosomal membrane.
AB  - Multivesicular bodies (MVBs) are late endosomal compartments containing luminal
      vesicles (MVB vesicles) that are formed by inward budding of the endosomal
      membrane. In budding yeast, MVBs are an important cellular mechanism for the
      transport of membrane proteins to the vacuolar lumen. This process requires a
      class E subset of vacuolar protein sorting (VPS) genes. VPS44 (allelic to NHX1)
      encodes an endosome-localized Na(+)/H(+) exchanger. The function of the VPS44
      exchanger in the context of vacuolar protein transport is largely unknown. Using
      a cell-free MVB formation assay system, we demonstrated that Nhx1p is required
      for the efficient formation of MVB vesicles in the late endosome. The recruitment
      of Vps27p, a class E Vps protein, to the endosomal membrane was dependent on
      Nhx1p activity and was enhanced by an acidic pH at the endosomal surface. Taken
      together, we propose that Nhx1p contributes to MVB formation by the recruitment
      of Vps27p to the endosomal membrane, possibly through Nhx1p antiporter activity.

PMID- 21896493
TI  - Changes in cortical morphology resulting from long-term amygdala damage.
AB  - The amygdala's contribution to emotion, cognition and behavior depends on its
      interactions with subcortical and cortical regions. Amygdala lesions result in
      altered functional activity in connected regions, but it is not known whether
      there might be long-term structural sequelae as well. We hypothesized that
      developmental bilateral amygdala lesions would be associated with specific gray
      matter morphometric abnormalities in the ventromedial prefrontal cortex (vmPFC),
      anterior cingulate cortex (ACC) and the ventral visual stream. We conducted
      regions of interest and vertex-based analyses of structural MRI data acquired in
      two patients with long-standing focal bilateral amygdala lesions (S.M. and A.P.),
      compared to gender- and age-matched healthy comparison subjects. Both patients
      showed significant proportional increases in gray matter volume of the vmPFC.
      Cortical thickness was increased in the vmPFC and ACC and decreased in the
      ventral visual stream. There were no morphometric changes in dorsolateral
      prefrontal cortex or dorsal visual stream cortices. These findings support the
      hypothesis that cortical regions strongly connected with the amygdala undergo
      morphometric changes with long-standing amygdala damage. This is the first
      evidence in humans of the remote alteration of brain morphology in association
      with amygdala lesions, and will help in interpreting the structural and
      functional consequences of amygdala pathology in neuropsychiatric disorders.

PMID- 21896494
TI  - An fMRI study of caring vs self-focus during induced compassion and pride.
AB  - This study examined neural activation during the experience of compassion, an
      emotion that orients people toward vulnerable others and prompts caregiving, and
      pride, a self-focused emotion that signals individual strength and heightened
      status. Functional magnetic resonance images (fMRI) were acquired as participants
      viewed 55 s continuous sequences of slides to induce either compassion or pride,
      presented in alternation with sequences of neutral slides. Emotion self-report
      data were collected after each slide condition within the fMRI scanner.
      Compassion induction was associated with activation in the midbrain
      periaqueductal gray (PAG), a region that is activated during pain and the
      perception of others' pain, and that has been implicated in parental nurturance
      behaviors. Pride induction engaged the posterior medial cortex, a region that has
      been associated with self-referent processing. Self-reports of compassion
      experience were correlated with increased activation in a region near the PAG,
      and in the right inferior frontal gyrus (IFG). Self-reports of pride experience,
      in contrast, were correlated with reduced activation in the IFG and the anterior
      insula. These results provide preliminary evidence towards understanding the
      neural correlates of important interpersonal dimensions of compassion and pride.
      Caring (compassion) and self-focus (pride) may represent core appraisals that
      differentiate the response profiles of many emotions.

PMID- 21896495
TI  - Impaired filtering of irrelevant information in dysphoria: an ERP study.
AB  - Behavioural findings have led to proposals that difficulties in attention and
      concentration in depression may have their roots in fundamental inhibitory
      impairments for irrelevant information. These impairments may be associated with
      reduced capacity to actively maintain relevant information to facilitate goal
      directed behaviour. In light of mixed data from behavioural studies, the current
      study using direct neural measurement, examines whether dysphoric individuals
      show poor filtering of irrelevant information and reduced working memory (WM)
      capacity for relevant information. Consistent with previous research, a sustained
      event-related potential (ERP) asymmetry, termed contra-lateral delay activity
      (CDA), was observed to be sensitive to WM capacity and the efficient filtering of
      irrelevant information from visual WM. We found a strong positive correlation
      between the efficiency of filtering irrelevant items and visual WM capacity.
      Specifically, dysphoric participants were poor at filtering irrelevant
      information, and showed reduced WM capacity relative to high capacity non
      dysphoric participants. Results support the hypothesis that impaired inhibition
      is a central feature of dysphoria and are discussed within the framework of
      cognitive and neurophysiological models of depression.

PMID- 21896496
TI  - How does the brain regulate negative bias to stigma?
AB  - The current study uses functional magnetic resonance imaging (fMRI) to examine
      whether regulating negative bias to stigmatized individuals has a unique neural
      activity profile from general emotion regulation. Participants were presented
      with images of stigmatized (e.g. homeless people) or non-stigmatized (e.g. a man
      holding a gun) social targets while undergoing fMRI and were asked either to
      maintain or regulate their emotional response. Their implicit bias toward these
      stigmatized group members was also measured. Analyses were conducted in both, an
      event-related fashion, considering the event to be the onset of regulation, and
      in a blocked-design fashion, considering the sustained activity throughout the 8
      s regulatory period. In the event-related (onset) analyses, participants showed
      more activity throughout the prefrontal cortex when initiating a regulatory
      response to stigmatized as compared with non-stigmatized images. This neural
      activity was positively correlated with their implicit bias. Interestingly, in
      the block (sustained) analyses, general emotion regulation elicited a more
      widespread pattern of neural activity as compared with stigma regulation. This
      activity was largely posterior, suggesting that general emotion regulation may
      engage more visuo-spatial processing as compared with stigma regulation. These
      findings suggest that regulating negative affect toward stigmatized targets may
      occur relatively more quickly than regulating negative affect toward non
      stigmatized targets.

PMID- 21896498
TI  - Solute clearance in CRRT: prescribed dose versus actual delivered dose.
AB  - BACKGROUND: Substantial efforts have been made toward defining the dose threshold
      of continuous renal replacement therapy (CRRT) associated with improved survival
      in critically ill patients with acute kidney injury. Published studies have used
      prescribed effluent rates, expressed as total effluent volume (TEV) per weight
      and unit time (mL/kg/h), as a surrogate for dose. The purpose of this study was
      to compare differences in CRRT dose based on prescribed effluent rate, measured
      TEV and direct measurement of urea and creatinine clearance. METHODS: We analyzed
      data that had been prospectively collected on 200 patients enrolled in a
      randomized trial comparing survival with a prescribed effluent rate of 20 mL/kg/h
      (standard dose) to 35 mL/kg/h (high dose) using pre-dilution continuous
      venovenous hemodiafiltration (CVVHDF). Filters were changed every 72 h. Blood
      urea nitrogen (BUN), serum creatinine (SCr), effluent urea nitrogen (EUN) and
      effluent creatinine (ECr) were collected daily. Actual delivered dose was
      calculated as: (EUN/BUN)*TEV for urea and (ECr/SCr)*TEV for creatinine. Data were
      available for 165 patients. RESULTS: In both groups, prescribed dose differed
      significantly from the measured TEV dose (P < 0.001). In the standard dose group,
      there was no difference between the measured TEV dose and actual delivered urea
      and creatinine clearances. However, in the high-dose group, measured TEV dose
      differed significantly from delivered urea clearance by 7.1% (P < 0.001) and
      creatinine clearance by 13.9% (P < 0.001). CONCLUSIONS: Dose based on prescribed
      effluent rate or measured TEV is a poor substitute for actual CVVHDF creatinine
      and urea clearance.

PMID- 21896497
TI  - The balance between feeling and knowing: affective and cognitive empathy are
      reflected in the brain's intrinsic functional dynamics.
AB  - Affective empathy (AE) is distinguished clinically and neurally from cognitive
      empathy (CE). While AE is selectively disrupted in psychopathy, autism is
      associated with deficits in CE. Despite such dissociations, AE and CE together
      contribute to normal human empathic experience. A dimensional measure of
      individual differences in AE 'relative to' CE captures this interaction and may
      reveal brain-behavior relationships beyond those detectable with AE and CE
      separately. Using resting-state fMRI and measures of empathy in healthy adults,
      we show that relative empathic ability (REA) is reflected in the brain's
      intrinsic functional dynamics. Dominance of AE was associated with stronger
      functional connectivity among social-emotional regions (ventral anterior insula,
      orbitofrontal cortex, amygdala, perigenual anterior cingulate). Dominance of CE
      was related to stronger connectivity among areas implicated in interoception,
      autonomic monitoring and social-cognitive processing (brainstem, superior
      temporal sulcus, ventral anterior insula). These patterns were distinct from
      those observed with AE and CE separately. Finally, REA and the strength of
      several functional connections were associated with symptoms of psychopathology.
      These findings suggest that REA provides a dimensional index of empathic function
      and pathological tendencies in healthy adults, which are reflected in the
      intrinsic functional dynamics of neural systems associated with social and
      emotional cognition.

PMID- 21896499
TI  - Association of hepatitis C virus infection and malnutrition-inflammation complex
      syndrome in maintenance hemodialysis patients.
AB  - BACKGROUND: Patients undergoing maintenance hemodialysis (MHD) have a
      significantly higher prevalence of hepatitis C virus (HCV) infection and
      malnutrition-inflammation complex syndrome (MICS). In the present study of
      Taiwanese MHD patients, we determined the clinical characteristics and influence
      of HCV infection on MICS by calculation of the malnutrition-inflammation score
      (MIS). METHODS: This was a prospective longitudinal study performed at a single
      hemodialysis (HD) center in Taiwan from September 2007 through March 2008. The
      study enrolled 58 patients (38%) in the active HCV group and 95 patients (62%) in
      the non-HCV group. The two or three weekly HD sessions of all patients were
      followed for 7 months. The MIS was assessed using 10 components, 7 from the
      conventional subjective global assessment of nutrition and 3 additional elements,
      body mass index, serum albumin and total iron-binding capacity. RESULTS: HD
      vintage and total MIS score were greater in patients with active HCV. The active
      HCV group had significantly longer dialysis vintage and lower total cholesterol
      but higher total MIS score than the non-HCV group. The MIS 5 score, a measure of
      major comorbid conditions (including number of years on dialysis), was also
      significantly higher in the active HCV group. CONCLUSION: MHD patients with
      active HCV infections have more severe MICS-associated metabolic and
      physiological disease than MHD patients without active HCV infection.

PMID- 21896500
TI  - Albumin-induced apoptosis of glomerular parietal epithelial cells is modulated by
      extracellular signal-regulated kinase 1/2.
AB  - BACKGROUND: The biological role(s) of glomerular parietal epithelial cells (PECs)
      is not fully understood in health or disease. Given its location, PECs are
      constantly exposed to low levels of filtered albumin, which is increased in
      nephrotic states. We tested the hypothesis that PECs internalize albumin and
      increased uptake results in apoptosis. METHODS: Confocal microscopy of
      immunofluorescent staining and immunohistochemistry were used to demonstrate
      albumin internalization in PECs and to quantitate albumin uptake in normal mice
      and rats as well as experimental models of membranous nephropathy, minimal change
      disease/focal segmental glomerulosclerosis and protein overload nephropathy.
      Fluorescence-activated cell sorting analysis was performed on immortalized
      cultured PECs exposed to fluorescein isothiocyanate (FITC)-labeled albumin in the
      presence of an endosomal inhibitor or vehicle. Apoptosis was measured by Hoechst
      staining in cultured PECs exposed to bovine serum albumin. Levels of
      phosphorylated extracellular signal-regulated kinase 1 and 2 (p-ERK1/2) were
      restored by retroviral infection of mitogen-activated protein kinase (MEK) 1/2
      and reduced by U0126 in PECs exposed to high albumin levels in culture and
      apoptosis measured by Hoechst staining. RESULTS: PECs internalized albumin
      normally, and this was markedly increased in all of the experimental disease
      models (P<0.05 versus controls). Cultured immortalized PECs also internalize FITC
      labeled albumin, which was reduced by endosomal inhibition. A consequence of
      increased albumin internalization was PEC apoptosis in vitro and in vivo.
      Candidate signaling pathways underlying these events were examined. Data showed
      markedly reduced levels of phosphorylated extracellular signal-regulated kinase 1
      and 2 (ERK1/2) in PECs exposed to high albumin levels in nephropathy and in
      culture. A role for ERK1/2 in limiting albumin-induced apoptosis was shown by
      restoring p-ERK1/2 by retroviral infection, which reduced apoptosis in cultured
      PECs, while a forced decrease of p-ERK1/2 through inhibition of MEK 1/2
      significantly increased albumin-induced PEC apoptosis. CONCLUSIONS: A normal role
      of PECs is to take up filtered albumin. However, this is increased in proteinuric
      glomerular diseases, leading to apoptosis through changes in ERK1/2.

PMID- 21896502
TI  - Prevalence and predictors of anemia in a population-based study of octogenarians
      and centenarians in Georgia.
AB  - BACKGROUND: Anemia has been associated with increased physical and financial
      costs and occurs more frequently in older individuals. Therefore, the primary
      objectives of this study were to examine the prevalence and possible predictors
      of anemia in the very old. METHODS: Hemoglobin was used to identify those with
      anemia in a group of centenarians and near centenarians (98+, n = 185) and
      octogenarians (n = 69), who were recruited as part of the population-based
      multidisciplinary Georgia Centenarian Study. Blood markers, including ferritin,
      vitamin B12, red blood cell folate, methylmalonic acid, creatinine, and C
      reactive protein, demographic variables, and medication and/or supplement usage
      were used to determine possible predictors of anemia. RESULTS: The prevalence of
      anemia was 26.2% in octogenarians and 52.1% in centenarians. Low serum albumin
      (<3.6 g/dL) and decreased estimated glomerular filtration rate (<45 mL/min/m(2))
      were predictors of anemia in centenarians. CONCLUSIONS: Anemia is a major health
      issue, particularly as people age. Because of the high prevalence of anemia in
      older individuals, awareness of the predictors associated with anemia becomes
      increasingly important so as to reduce the negative consequences associated with
      it and allow for the identification of steps that can be taken to correct anemia,
      including managing chronic disease.

PMID- 21896503
TI  - Effect of aging on power output properties in rat skinned cardiac myocytes.
AB  - Aging is generally associated with a decline in several indices of cardiac
      function. The cellular mechanisms for this decline are not completely understood.
      The ability of the myocardium to perform external work (power output) is a
      critical aspect of ventricular function. The purpose of this study was to
      determine the effect of aging on loaded shortening and power output properties.
      We measured force-velocity properties in permeabilized (skinned) myocytes from
      the hearts of 9-, 24-, and 33-month-old male Fisher 344 * Brown Norway F1 hybrid
      rats (F344BN) during loaded contractions using a force-clamp technique. Power
      output was calculated by multiplying force and shortening velocity values. We
      found that peak power output normalized to maximal force was significantly
      decreased by 18% and 31% in myocytes from 24- and 33-month-old group,
      respectively, compared with 9-month group (p < .05). These results suggest that
      aging is associated with a significant decrease in the ability of the myocardium
      to do work.

PMID- 21896501
TI  - Intracellular transport of plant viruses: finding the door out of the cell.
AB  - Plant viruses are a class of plant pathogens that specialize in movement from
      cell to cell. As part of their arsenal for infection of plants, every virus
      encodes a movement protein (MP), a protein dedicated to enlarging the pore size
      of plasmodesmata (PD) and actively transporting the viral nucleic acid into the
      adjacent cell. As our knowledge of intercellular transport has increased, it has
      become apparent that viruses must also use an active mechanism to target the
      virus from their site of replication within the cell to the PD. Just as viruses
      are too large to fit through an unmodified plasmodesma, they are also too large
      to be freely diffused through the cytoplasm of the cell. Evidence has accumulated
      now for the involvement of other categories of viral proteins in intracellular
      movement in addition to the MP, including viral proteins originally associated
      with replication or gene expression. In this review, we will discuss the
      strategies that viruses use for intracellular movement from the replication site
      to the PD, in particular focusing on the role of host membranes for intracellular
      transport and the coordinated interactions between virus proteins within cells
      that are necessary for successful virus spread.

PMID- 21896504
TI  - Influenza-like illness in Norway: clinical course, attitudes towards vaccination
      and preventive measures during the 2009 pandemic.
AB  - OBJECTIVES: To document clinical characteristics of influenza-like illness,
      reported use of health preventive measures and attitudes towards vaccination
      among patients with influenza-like illness in general practice during the
      influenza pandemic in 2009. METHODS: Cross-sectional survey in general practice.
      Patients, who were identified as having influenza-like illness during the peak of
      the influenza pandemic activity in Norway, were eligible for inclusion in the
      study. A questionnaire was sent 2-4 weeks after the patients visit to the GP with
      influenza-like illness diagnosis during October to December 2009, from general
      practices in Norway. A sample of responders >18 years also had a blood test to
      check for serological response to the pandemic H1N1 virus. RESULTS:
      Questionnaires were sent to 1324 patients, and 357 (27%) were returned. Fever
      (91% versus 49%, P < 0.01), cough (85% versus 73%, P = 0.016) and
      gastrointestinal symptoms (58% versus 38%, P < 0.01) were more frequent in the
      age group <18 years compared to older patients. Serological H1N1 responses were
      analysed in 72 patients; 34 (47%) were positive (haemagglutination inhibition
      assay titres >= 40). There were no statistically significant differences in
      symptoms between seropositive and seronegative patients. Women reported better
      adherence to personal protective measures, such as hand washing and cough
      etiquette than men. Women were also more concerned about possible adverse effects
      of the pandemic influenza vaccine than men. CONCLUSIONS: Discrimination between
      influenza and other viral upper respiratory tract infections is difficult in
      daily clinical practice, even during an influenza pandemic. A gender difference
      was found in reported precautions to prevent influenza.

PMID- 21896505
TI  - Complications of acute rhinosinusitis in The Netherlands.
AB  - BACKGROUND: Despite the evidence demonstrating that antibiotics are of little
      benefit in acute rhinosinusitis (ARS), GPs continue to prescribe them, possibly
      in an attempt to prevent potentially dangerous complications. In this study, we
      present epidemiological data about the incidence, course and severity of such
      complications in the Netherlands. METHODS: This retrospective cohort study
      included all patients hospitalized in The Netherlands in 2004 with a complication
      of ARS. Records were made of the symptoms of ARS and the complication,
      demographics, medical history, medical treatment preceding hospitalization,
      diagnostic techniques, therapeutic management, course and outcome. RESULTS: Forty
      seven patients with 48 complications (16 intracranial and 32 orbital) were
      included. In the intracranial group (mean age 35.9 years), six patients had been
      treated with oral antibiotics prior to hospitalization. While hospitalized, all
      patients were treated with intravenous antibiotics and 15 underwent surgery.
      Eight patients recovered fully after treatment, three patients had residual
      symptoms and three patients died (missing data: 2). Of the 31 patients with
      orbital complications (mean age 17.4 years), 14 received oral antibiotics before
      admission. While hospitalized, all patients were treated with intravenous
      antibiotics and 13 underwent surgery. Twenty-seven patients recovered fully and
      two had residual symptoms (missing data: 2). CONCLUSIONS: Severe ARS
      complications occur in an otherwise healthy population in an estimated 1:12,000
      paediatric and 1:32,000 adult cases in the Netherlands. Our study suggests that
      antibiotic treatment of ARS in general practice does not play a role in
      preventing complications.

PMID- 21896506
TI  - Help-seeking behaviour of Serbian women who experienced intimate partner
      violence.
AB  - OBJECTIVE: This study aimed to identify whom women in Serbia approach for help in
      case of intimate partner violence (IPV), their reasons for seeking help and their
      satisfaction with the received help. METHODS: A cross-sectional, population-based
      household survey of a random sample of women aged 15-49 years was conducted in
      Belgrade (WHO Multi-country Study on Women's Health and Domestic Violence against
      Women). A standard questionnaire was administered by trained interviewers through
      face-to-face interviews. RESULTS: The questionnaire was completed by 1456 women
      and 1196 of them ever had an intimate partner. Almost one in four ever-partnered
      women reported experiencing either physical and/or sexual violence, at least once
      in their life. Among these abused women, ~ 22% had ever sought help from formal
      institutions. Police and health services were most commonly approached (12% and
      10% of abused women, respectively). Satisfaction with services was highest for
      health services and legal advice and lowest for police and social services. Women
      sought help especially when violence had a severe impact on them or when they saw
      that their children suffered. Women who did not seek help stated that they
      believed that the violence was bearable or had ended. Other reasons for not
      seeking help were fear of undesirable consequences of seeking help and lack of
      trust in institutions. CONCLUSIONS: From the abused women's perspective, health
      care services are the institutions with the highest potential to help women in
      cases of IPV. Developing a comprehensive health sector response is of critical
      importance to ensure appropriate care and referral.

PMID- 21896507
TI  - wapRNA: a web-based application for the processing of RNA sequences.
AB  - SUMMARY: mRNA/miRNA-seq technology is becoming the leading technology to globally
      profile gene expression and elucidate the transcriptional regulation mechanisms
      in living cells. Although there are many tools available for analyzing RNA-seq
      data, few of them are available as easy accessible online web tools for
      processing both mRNA and miRNA data for the RNA-seq based user community. As
      such, we have developed a comprehensive web application tool for processing mRNA
      seq and miRNA-seq data. Our web tool wapRNA includes four different modules: mRNA
      seq and miRNA-seq sequenced from SOLiD or Solexa platform and all the modules
      were tested on previously published experimental data. We accept raw sequence
      data with an optional reads filter, followed by mapping and gene annotation or
      miRNA prediction. wapRNA also integrates downstream functional analyses such as
      Gene Ontology, KEGG pathway, miRNA targets prediction and comparison of gene's or
      miRNA's different expression in different samples. Moreover, we provide the
      executable packages for installation on user's local server. AVAILABILITY: wapRNA
      is freely available for use at http://waprna.big.ac.cn. The executable packages
      and the instruction for installation can be downloaded from our web site.
      CONTACT: husn@big.ac.cn; songshh@big.ac.cn. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 21896508
TI  - Correlated evolution of transcription factors and their binding sites.
AB  - MOTIVATION: The interaction between transcription factor (TF) and transcription
      factor binding site (TFBS) is essential for gene regulation. Mutation in either
      the TF or the TFBS may weaken their interaction and thus result in abnormalities.
      To maintain such vital interaction, a mutation in one of the interacting partners
      might be compensated by a corresponding mutation in its binding partner during
      the course of evolution. Confirming this co-evolutionary relationship will guide
      us in designing protein sequences to target a specific DNA sequence or in
      predicting TFBS for poorly studied proteins, or even correcting and rescuing
      disease mutations in clinical applications. RESULTS: Based on six, publicly
      available, experimentally validated TF-TFBS binding datasets for the basic Helix
      Loop-Helix (bHLH) family, Homeo family, High-Mobility Group (HMG) family and
      Transient Receptor Potential channels (TRP) family, we showed that the evolutions
      of the TFs and their TFBSs are significantly correlated across eukaryotes. We
      further developed a mutual information-based method to identify co-evolved
      protein residues and DNA bases. This research sheds light on the dynamic
      relationship between TF and TFBS during their evolution. The same principle and
      strategy can be applied to co-evolutionary studies on protein-DNA interactions in
      other protein families. AVAILABILITY: All the datasets, scripts and other related
      files have been made freely available at: http://jjwanglab.org/co-evo. CONTACT:
      junwen@uw.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at
      Bioinformatics online.

PMID- 21896510
TI  - Robust relative compression of genomes with random access.
AB  - MOTIVATION: Storing, transferring and maintaining genomic databases becomes a
      major challenge because of the rapid technology progress in DNA sequencing and
      correspondingly growing pace at which the sequencing data are being produced.
      Efficient compression, with support for extraction of arbitrary snippets of any
      sequence, is the key to maintaining those huge amounts of data. RESULTS: We
      present an LZ77-style compression scheme for relative compression of multiple
      genomes of the same species. While the solution bears similarity to known
      algorithms, it offers significantly higher compression ratios at compression
      speed over an order of magnitude greater. In particular, 69 differentially
      encoded human genomes are compressed over 400 times at fast compression, or even
      1000 times at slower compression (the reference genome itself needs much more
      space). Adding fast random access to text snippets decreases the ratio to ~300.
      AVAILABILITY: GDC is available at http://sun.aei.polsl.pl/gdc. CONTACT:
      sebastian.deorowicz@polsl.pl. SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 21896509
TI  - SpliceTrap: a method to quantify alternative splicing under single cellular
      conditions.
AB  - MOTIVATION: Alternative splicing (AS) is a pre-mRNA maturation process leading to
      the expression of multiple mRNA variants from the same primary transcript. More
      than 90% of human genes are expressed via AS. Therefore, quantifying the
      inclusion level of every exon is crucial for generating accurate transcriptomic
      maps and studying the regulation of AS. RESULTS: Here we introduce SpliceTrap, a
      method to quantify exon inclusion levels using paired-end RNA-seq data. Unlike
      other tools, which focus on full-length transcript isoforms, SpliceTrap
      approaches the expression-level estimation of each exon as an independent
      Bayesian inference problem. In addition, SpliceTrap can identify major classes of
      alternative splicing events under a single cellular condition, without requiring
      a background set of reads to estimate relative splicing changes. We tested
      SpliceTrap both by simulation and real data analysis, and compared it to state-of
      the-art tools for transcript quantification. SpliceTrap demonstrated improved
      accuracy, robustness and reliability in quantifying exon-inclusion ratios.
      CONCLUSIONS: SpliceTrap is a useful tool to study alternative splicing
      regulation, especially for accurate quantification of local exon-inclusion ratios
      from RNA-seq data. AVAILABILITY AND IMPLEMENTATION: SpliceTrap can be implemented
      online through the CSH Galaxy server http://cancan.cshl.edu/splicetrap and is
      also available for download and installation at
      http://rulai.cshl.edu/splicetrap/. CONTACT: michael.zhang@utdallas.edu.
      SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics
      online.

PMID- 21896511
TI  - A unified front against COPD: clinical practice guidelines from the American
      College of Physicians, the American College of Chest Physicians, the American
      Thoracic Society, and the European Respiratory Society.

PMID- 21896512
TI  - "The cruelest lies are often told in silence".

PMID- 21896513
TI  - Obstructive? Restrictive? Or a ventilatory impairment?

PMID- 21896514
TI  - Is atherosclerotic heart disease in COPD a distinct phenotype?

PMID- 21896515
TI  - Point: efficacy of bronchial thermoplasty for patients with severe asthma. Is
      there sufficient evidence? Yes.

PMID- 21896516
TI  - Counterpoint: efficacy of bronchial thermoplasty for patients with severe asthma.
      Is there sufficient evidence? Not yet.

PMID- 21896518
TI  - The Fontana paradoxical reflex?
AB  - This commentary describes the "deflation cough" caused by deep lung deflations.
      Deflation cough is a paradoxical reflex similar to that described by Henry Head
      in 1889 for lung inflations that probably is mediated by the same sensors and
      afferent fibers in the lungs and activated by gastroesophageal reflux. We discuss
      how this reflex must be self-limiting, the general role of paradoxical reflexes
      in the body, and the possible clinical significance of deflation cough.

PMID- 21896519
TI  - The role of the clinical and translational science awards program in improving
      the quality and efficiency of clinical research.
AB  - Recognizing the need to increase the efficiency and quality of translating basic
      discovery into treatment and prevention strategies for patients and the public,
      the National Institutes of Health (NIH) announced the Clinical and Translational
      Science Awards (CTSAs) in 2006. Academic health centers that competed
      successfully for these awards agreed to work as a consortium and in cooperation
      with the NIH to improve the translation process by training the next generation
      of investigators to work in interdisciplinary teams, developing public-private
      partnerships in the movement of basic discovery to preclinical and clinical
      studies and trials, improving clinical research management, and engaging with
      communities to ensure their involvement in shaping research questions and in
      implementing research results. The CTSAs have addressed the crucial need to
      improve the quality and efficiency of clinical research by (1) providing training
      for clinical investigators and for bench researchers to facilitate their
      participation in the clinical and translational research environment, (2)
      developing more systematic approaches to clinical research management, and (3)
      engaging communities as active participants in the design and conduct of clinical
      research studies and trials and as leaders in implementing health advances that
      are of high importance to them. We provide an overview of the CTSA activities
      with attention to these three areas, which are essential to developing efficient
      clinical research efforts and effective implementation of research results on a
      national level.

PMID- 21896517
TI  - Statins and brain dysfunction: a hypothesis to reduce the burden of cognitive
      impairment in patients who are critically ill.
AB  - Delirium is a frequent form of acute brain dysfunction in patients who are
      critically ill and is associated with poor clinical outcomes, including a
      critical illness brain injury that may last for months to years. Despite
      widespread recognition of significant adverse outcomes, pharmacologic approaches
      to prevent or treat delirium during critical illness remain unproven. We
      hypothesize that commonly prescribed statin medications may prevent and treat
      delirium by targeting molecular pathways of inflammation (peripheral and central)
      and microglial activation that are central to the pathogenesis of delirium.
      Systemic inflammation, a principal mechanism of injury, for example, in sepsis,
      acute respiratory distress syndrome, and other critical illnesses, can cause
      neuronal apoptosis, blood-brain barrier injury, brain ischemia, and microglial
      activation. We hypothesize that the known pleiotropic effects of statins, which
      attenuate such neuroinflammation, may redirect microglial activation and promote
      an antiinflammatory phenotype, thereby offering the potential to reduce the
      public health burden of delirium and its associated long-term cognitive injury.

PMID- 21896521
TI  - The law and its interaction with medical ethics in end-of-life decision making.
AB  - The previous two articles in this series explored the historical and theoretical
      development of medical decision making from initial reliance on medical
      beneficence to a more recent emphasis on patient autonomy. The law of withholding
      and withdrawal of treatment has much in common with medical ethics. It is based
      on concerns about patient autonomy expressed by courts, legislatures, and the
      executive branch of the government. Legally, the patient's right of self
      determination has been based on a variety of sources ranging from state and
      federal constitutions to the common law of torts and from cases to statutes and
      regulations. Understanding the various sources of the law, the distinctions among
      those sources, and the interaction of the branches of government in this context
      assists in understanding the law itself. In our federalist system of government,
      significant legal variations can exist among the states, but although technically
      valid, excessive concern about compliance with the precise contours of each
      state's statute when surrogate decision makers are engaging in bedside
      deliberations is unnecessary. Regardless of source or precise legal contours, the
      overall goal, which neither the physician nor the patient's surrogate or proxy
      decision makers should forget, is to honor what the patient would want to have
      done. Physicians and attorneys will agree on that as a matter of both ethics and
      the law.

PMID- 21896520
TI  - Alternatively activated macrophages and airway disease.
AB  - Macrophages are the most abundant immune cell population in normal lung tissue
      and serve critical roles in innate and adaptive immune responses as well as the
      development of inflammatory airway disease. Studies in a mouse model of chronic
      obstructive lung disease and translational studies of humans with asthma and COPD
      have shown that a special subset of macrophages is required for disease
      progression. This subset is activated by an alternative pathway that depends on
      production of IL-4 and IL-13, in contrast to the classic pathway driven by
      interferon-gamma. Recent and unexpected results indicate that alternatively
      activated macrophages (AAMs) can also become a major source of IL-13 production
      and, thereby, drive the increased mucus production and airway hyperreactivity
      that is characteristic of airway disease. Although the normal and abnormal
      functions of AAMs are still being defined, it is already apparent that markers of
      this immune cell subset can be useful to guide stratification and treatment of
      patients with chronic airway diseases. Here, we review basic and clinical
      research studies that highlight the importance of AAMs in the pathogenesis of
      asthma, COPD, and other chronic airway diseases.

PMID- 21896522
TI  - Aerosol therapy for obstructive lung diseases: device selection and practice
      management issues.
AB  - Inhaled aerosol therapies are the mainstay of treatment of obstructive lung
      diseases. Aerosol devices deliver drugs rapidly and directly into the airways,
      allowing high local drug concentrations while limiting systemic toxicity. While
      numerous clinical trials, literature reviews, and expert panel guidelines inform
      the choice of inhalational drugs, deciding which aerosol device (ie, metered-dose
      inhaler, nebulizer, or dry powder inhaler) best suits a given patient and
      clinical setting can seem arbitrary and confusing. Similar confusion regarding
      Current Procedural Terminology (CPT) coding for administration of aerosol
      therapies can lead to lost revenue from underbilling and wasted administrative
      effort handling denied claims. This article reviews the aerosol devices currently
      available, discusses their relative merits in various clinical settings, and
      summarizes appropriate CPT coding for aerosol therapy.

PMID- 21896523
TI  - Pulmonary histoplasmosis presenting with the reversed halo sign on high
      resolution CT scan.
AB  - We describe the case of a 23-year-old man with pulmonary histoplasmosis whose
      high-resolution CT scan demonstrated the reversed halo sign. We also extensively
      review the literature about this CT scan sign. The reversed halo sign has been
      described in a number of diseases, both infectious and noninfectious. However, to
      our knowledge, this is the first reported case of pulmonary histoplasmosis
      presenting with this radiologic finding.

PMID- 21896524
TI  - The many faces of Merlin: IgG4-associated pulmonary-renal disease.
AB  - Pulmonary-renal syndrome is a common and serious disorder with a broad
      differential diagnosis. We describe a case of a middle-aged man presenting with
      interstitial pulmonary disease and severe renal impairment caused by a
      hypocomplementemic immune-complex-mediated interstitial nephritis. Serum levels
      of IgG4 were elevated, and renal biopsy specimens revealed the presence of
      interstitial IgG4(+) plasma cells. There was a rapid improvement of both
      pulmonary and renal abnormalities after the initiation of corticosteroids. To our
      knowledge, this report is the first to show interstitial pulmonary disease in
      association with interstitial kidney disease as the predominant and presenting
      symptoms of IgG4-related disease.

PMID- 21896526
TI  - A 30-year-old woman with intermittent cough and a mass-like opacity in the right
      upper lobe.

PMID- 21896525
TI  - Toxicology in the ICU: Part 1: general overview and approach to treatment.
AB  - Poisonings, adverse drug effects, and envenomations continue to be commonly
      encountered. Patients often present critically ill and warrant ICU admission.
      Many other patients who are initially stable have the potential for rapid
      deterioration and require continuous cardiopulmonary and neurologic monitoring.
      Given the potential for rapid deterioration, and because patients need continuous
      monitoring, ICU admission is frequently required. This article is the first of a
      three-part series to be published in CHEST; it discusses general management,
      laboratory tests, enhanced elimination, and emerging therapies. The second
      article will address the management of specific overdoses; the last will cover
      plants, mushrooms, envenomations, and heavy metals.

PMID- 21896527
TI  - 74-year-old man from the pacific northwest with fever and a lung mass.

PMID- 21896528
TI  - Persistent dyspnea in a 59-year-old woman receiving immunosuppressants.

PMID- 21896529
TI  - Pulmonary graft dysfunction and elevated pulmonary pressures.

PMID- 21896530
TI  - Minimally invasive closure of bronchopleural fistulas.

PMID- 21896531
TI  - Flavocoxid and hypersensitivity pneumonitis.

PMID- 21896532
TI  - Can pulmonary arterial hypertension be diagnosed by an elevated pulmonary
      capillary wedge pressure outside of the guideline criteria?

PMID- 21896533
TI  - Cytokine gene expression after lung cancer resection may be affected by the
      choice of surgical access.

PMID- 21896534
TI  - Evidence incorporating patients' values.

PMID- 21896535
TI  - A survey of current bronchoscopy practices in Canada: a dearth of evidence or
      evidence-based practice?

PMID- 21896536
TI  - Clinical characteristics and major comorbidities in heart failure patients more
      than 85 years of age compared with younger age groups.
AB  - AIMS: Heart failure (HF) is increasingly prevalent among the growing number of
      elderly people, but not well studied. We sought to evaluate disease pattern and
      importance of prognostic factors among very elderly patients with HF. METHODS AND
      RESULTS: Among 8507 patients screened for entry into two studies on HF, we
      analysed the clinical characteristics, major comorbidities and prognostic factors
      in 825 patients older than 85 years (very elderly) compared with younger age
      groups. Adjusted hazard ratios [HR (95% confidence intervals)] of long-term
      mortality were calculated using Cox models. The very elderly were more often
      female (60 vs. 26%) and had a higher prevalence of preserved ejection fraction
      (53 vs. 36%) compared with patients younger than 65 years (P< 0.001). The
      prevalence of cardiovascular comorbidities increased with advancing age only
      until the seventh decade and then declined, resulting in the lowest prevalence of
      diabetes (12 vs. 16%, P< 0.001), hypertension (20 vs. 26%, P< 0.001), ischaemic
      heart disease (42 vs. 53%, P< 0.001), and peripheral artery disease (4 vs. 6%, P=
      0.017) among the very elderly compared with patients aged <85 years. Non
      cardiovascular comorbidities generally increased linearly with age. Long-term
      mortality was associated with atrial fibrillation [HR = 1.30 (1.06-1.60), P=
      0.013] with greater prognostic importance in the very elderly, while ejection
      fraction, diabetes [HR = 1.31 (1.01-1.61), P= 0.04], and renal insufficiency [HR
      = 1.36 (1.13-0.63), P< 0.0001] had less prognostic importance than in younger
      patients (P for interactions <0.003). CONCLUSION: The prevalence of
      cardiovascular comorbidities is lower in very elderly HF patients and has
      different prognostic importance.

PMID- 21896537
TI  - Clinical trials update from the European Society of Cardiology Heart Failure
      meeting 2011: TEHAF, WHICH, CARVIVA, and atrial fibrillation in GISSI-HF and
      EMPHASIS-HF.
AB  - This article provides information and a commentary on key trials relevant to the
      pathophysiology, prevention, and treatment of heart failure (HF) presented at the
      European Society of Cardiology Heart Failure meeting held in Gothenburg, Sweden
      in May 2011. Unpublished reports should be considered as preliminary, since
      analyses may change in the final publication. In the TEHAF study, use of the
      Health Buddy((r)) monitoring system failed to reduce the number of HF admissions
      compared with usual care but a subgroup of patients with more recently diagnosed
      HF may have benefited. In the WHICH study, some reductions in the rate of
      hospital stay were observed in patients who underwent a nurse-led home-based
      intervention programme following a hospital admission for an acute HF
      exacerbation, compared with patients who were followed in a specialized
      outpatient clinic. Results from CARVIVA-HF suggest that ivabradine alone or in
      combination with carvedilol is safe and effective for improving exercise capacity
      and quality of life in HF patients on optimized angiotensin-converting enzyme
      inhibitor therapy. In the GISSI-HF study there was no difference in atrial
      fibrillation (AF) occurrence between the n-3 polyunsaturated fatty acids and
      placebo groups. In EMPHASIS-HF the incidence of new onset AF or flutter was
      reduced in patients with mild HF randomized to eplerenone compared with placebo.

PMID- 21896538
TI  - Genetic basis of end-stage hypertrophic cardiomyopathy.
AB  - AIMS: Hypertrophic cardiomyopathy (HCM) is characterized by a heterogeneous
      presentation and clinical course. A minority of HCM patients develop end-stage
      HCM and require cardiac transplantation. The genetic basis of end-stage HCM is
      unknown but small series, isolated case reports and animal models have related
      the most aggressive heart failure course with the presence of multiple mutations.
      METHODS AND RESULTS: Twenty-six patients (age 40.4 +/- 14.5 years; 46% male)
      transplanted for end-stage HCM underwent genetic screening of 10 HCM-related
      genes (MYH7, MYBPC3, TNNT2, TNNI3, TPM1, TNNC1, MYL3, MYL2, ACTC, LDB3).
      Additional genetic screening of LAMP2/PRKAG2 and mitochondrial DNA (mtDNA) was
      performed in four and three cases, respectively. Findings were correlated with
      clinical and histological features. Pathogenic mutations were identified in 15
      patients (58%). Thirteen patients (50%) had mutations in sarcomeric genes (six in
      MYH7, three in MYBPC3, two in MYL2, one in TNNI3, and one in MYL3) and two
      patients had mutations in LAMP2. Only three patients (13%) had double mutations
      and all in homozygosis. Except for a more frequent family history of HCM,
      patients with mutations in sarcomeric genes did not show any clinical feature
      that distinguished them from patients without mutations in these genes.
      Evaluation of 44 relatives from 12 families identified 13 mutation carriers, 9 of
      whom had an overt HCM phenotype. CONCLUSION: Heart transplanted HCM has a
      heterogeneous genetic background where multiple mutations are uncommon. The
      clinical course of HCM is not primarily dependent on the presence of multiple
      sarcomeric mutations. Clinical and genetic evaluation of relatives does not
      support differential clinical management in HCM based on genetics.

PMID- 21896539
TI  - Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III
      colon cancer: final results from the X-ACT trial with analysis by age and
      preliminary evidence of a pharmacodynamic marker of efficacy.
AB  - BACKGROUND: This multicenter randomized trial compared oral capecitabine with
      bolus i.v. 5-fluorouracil (5-FU)/folinic acid (FA) as adjuvant therapy for stage
      III colon cancer. PATIENTS AND METHODS: Patients were assigned to 24 weeks of
      capecitabine 1250 mg/m(2) twice daily on days 1-14 every 3 weeks or 5-FU/FA (Mayo
      Clinic regimen). The primary end point was disease-free survival (DFS). RESULTS:
      The intent-to-treat population received capecitabine (n = 1004) or 5-FU/FA (n =
      983). With a median follow-up of 6.9 years, capecitabine was at least equivalent
      to 5-FU/FA in terms of DFS [hazard ratio (HR) = 0.88; 95% confidence interval
      (CI) 0.77-1.01] and overall survival (OS) (HR = 0.86; 95% CI 0.74-1.01); the 95%
      CI upper limits were significantly less than the predefined noninferiority
      margins of 1.20 (P < 0.0001) and 1.14 (P < 0.001), respectively. This pattern was
      maintained in all subgroups, including patients aged >= 70 years. Preplanned
      multivariate analyses showed that capecitabine had statistically significant
      beneficial effects on DFS (P = 0.021) and OS (P = 0.020) versus 5-FU/FA. A post
      hoc analysis suggested that the occurrence of hand-foot syndrome may be
      associated with better outcomes in capecitabine recipients. CONCLUSION: Oral
      capecitabine is an effective alternative to bolus 5-FU/FA as adjuvant treatment
      of patients with stage III colon cancer with efficacy benefits maintained at 5
      years and in older patients.

PMID- 21896541
TI  - Cytotoxic drugs for patients with breast cancer in the era of targeted treatment:
      back to the future?
AB  - BACKGROUND: Despite current trend of targeted therapy development, cytotoxic
      agents are a mainstay of treatment of patients with breast cancer. We reviewed
      recent advances in cytotoxic therapy for patients with metastatic breast cancer
      (MBC). MATERIALS AND METHODS: Medline searches were conducted for English
      language studies using the term 'MBC' and 'cytotoxic drugs'. The data search was
      restricted to the period 2000-2011. RESULTS: Several novel cytotoxic compounds,
      all microtubule inhibitors, have been approved for clinical use in MBC: (i) nab
      paclitaxel, reported to improve tumour response and decrease hypersensitivity
      reactions in comparison with other taxanes; (ii) ixabepilone, shown to have
      clinical benefit in taxane- and anthracycline-resistant disease and (iii)
      eribulin, shown to improve overall survival in heavily pre-treated patients, when
      compared with best available standard treatment. Agents, such as larotaxel,
      vinflunine, trabectidin and formulations, including cationic liposomal paclitaxel
      or paclitaxel poliglumex, are currently under evaluation in phase II/III trials.
      CONCLUSION: Toxicity and chemotherapy resistance are still major limitations in
      the treatment of patients with MBC. Further research into new cytotoxic compounds
      is needed in order to maximise benefit, whilst minimising toxicity.

PMID- 21896540
TI  - Cationic liposomal paclitaxel plus gemcitabine or gemcitabine alone in patients
      with advanced pancreatic cancer: a randomized controlled phase II trial.
AB  - BACKGROUND: Paclitaxel embedded in cationic liposomes (EndoTAGTM-1; ET) is an
      innovative agent targeting tumor endothelial cells. This randomized controlled
      phase II trial evaluated the safety and efficacy of ET in combination with
      gemcitabine (GEM) in advanced pancreatic cancer (PDAC). PATIENTS AND METHODS:
      Chemotherapy-naive patients with locally advanced or metastatic disease were
      randomly assigned to receive weekly GEM 1000 mg/m(2) or GEM plus twice-weekly ET
      11, 22 or 44 mg/m(2) for 7 weeks. After a safety run-in of 100 patients, a second
      cohort continued treatment. End points included overall survival (OS),
      progression-free survival (PFS), tumor response and safety. RESULTS: Two hundred
      and twelve patients were randomly allocated to the study and 200 were treated
      (80% metastatic, 20% locally advanced). Adverse events were manageable and
      reversible. Transient thrombocytopenia and infusion reactions with chills and
      pyrexia mostly grade 1 or 2 occurred in the ET groups. Disease control rate after
      the first treatment cycle was 43% with GEM and 60%, 65% and 52% in the GEM + ET
      cohorts. Median PFS reached 2.7 compared with 4.1, 4.6 and 4.4 months,
      respectively. Median OS was 6.8 compared with 8.1, 8.7 and 9.3 months,
      respectively. CONCLUSIONS: Treatment of advanced PDAC with GEM + ET was generally
      well tolerated. GEM + ET showed beneficial survival and efficacy. A randomized
      phase III trial should confirm this positive trend.

PMID- 21896542
TI  - Imaging bone metastases in breast cancer: evidence on comparative test accuracy.
AB  - BACKGROUND: Numerous imaging modalities may be used to detect bone metastases
      (BM) in women with breast cancer. METHODS: Systematic evidence review, including
      quality appraisal, of studies reporting on comparative imaging accuracy for
      detection of BM from breast cancer. RESULTS: Eligible studies (N = 16) included
      breast cancer subjects who had imaging evaluation for suspected BM or for
      staging/restaging in suspected local or distant relapse. Median prevalence of BM
      was 34.0% (range 10.0%-66.7%). There was substantial heterogeneity in the quality
      of reference standards and in the prevalence of BM, which could account for some
      of the differences in reported comparative accuracy. Most frequently, bone scan
      (BS) was compared with newer imaging modalities in subjects selected to both
      tests; therefore, results could be affected by selection bias. There was some
      evidence that positron emission tomography (PET), and limited evidence that
      PET/computed tomography (CT), CT, and magnetic resonance imaging (MRI), may
      provide small increments in accuracy relative to BS as add-on tests; there was
      little evidence regarding single photon emission computed tomography or whole
      body MRI. CONCLUSIONS: There is some evidence of enhanced incremental accuracy
      for some of the above-mentioned tests where used as add-on in subjects selected
      to more than one imaging modality, with little evidence to support their
      application as a replacement to BS in first-line imaging of BM. PET/CT appears to
      have high accuracy and is recommended for further evaluation.

PMID- 21896545
TI  - Expanding reproductive lifespan: a cost-effectiveness study on oocyte freezing.
AB  - BACKGROUND: The average age of women bearing their first child has increased
      strongly. This is an important reproductive health problem as fertility declines
      with increasing female age. Unfortunately, IVF using fresh oocytes cannot
      compensate for this age-related fertility decline. Oocyte freezing could be a
      solution. METHODS: We used the Markov model to estimate the cost-effectiveness of
      three strategies for 35-year-old women who want to postpone pregnancy till the
      age of 40: Strategy 1: women undergo three cycles of ovarian hyperstimulation at
      age 35 for oocyte freezing, then at age 40, use these frozen oocytes for IVF;
      Strategy 2: women at age 40 attempt to conceive without treatment; and the
      reference strategy: women at age 40 attempt to conceive and, if not pregnant
      after 1 year, undergo IVF. Sensitivity analyses were carried out to investigate
      assumptions of the model and to identify which model inputs had most impact on
      the results. RESULTS: Oocyte freezing (Strategy 1) resulted in a live birth rate
      of 84.5% at an average cost of ?10,419. Natural conception (Strategy 2) resulted
      in a live birth rate of 52.3% at an average cost of ?310 per birth. IVF (the
      reference strategy) resulted in a cumulative live birth rate of 64.6% at an
      average cost of ?7798. The cost per additional live birth for the oocyte freezing
      strategy was ?13,156 compared to the IVF strategy. If at least 61% of the women
      return to collect their oocytes, and if there is a willingness to pay ?19,560
      extra per additional live birth, the oocyte freezing strategy is the most cost
      effective strategy. CONCLUSION: Oocyte freezing is more cost effective compared
      to IVF, if at least 61% of the women return to collect their oocytes and if one
      is willing to pay ?19,560 extra per additional live birth. Our Markov model shows
      that, considering all the used assumptions, oocyte freezing provides more value
      for money than IVF.

PMID- 21896543
TI  - Cost comparison of axillary sentinel lymph node detection and axillary
      lymphadenectomy in early breast cancer. A national study based on a prospective
      multi-institutional series of 985 patients 'on behalf of the Group of Surgeons
      from the French Unicancer Federation'.
AB  - BACKGROUND: Our objective was to assess the global cost of the sentinel lymph
      node detection [axillary sentinel lymph node detection (ASLND)] compared with
      standard axillary lymphadenectomy [axillary lymph node dissection (ALND)] for
      early breast cancer patients. PATIENTS AND METHODS: We conducted a prospective,
      multi-institutional, observational, cost comparative analysis. Cost calculations
      were realized with the micro-costing method from the diagnosis until 1 month
      after the last surgery. RESULTS: Eight hundred and thirty nine patients were
      included in the ASLND group and 146 in the ALND group. The cost generated for a
      patient with an ASLND, with one preoperative scintigraphy, a combined method for
      sentinel node detection, an intraoperative pathological analysis without
      lymphadenectomy, was lower than the cost generated for a patient with
      lymphadenectomy [? 2947 (sigma = 580) versus ? 3331 (sigma = 902); P = 0.0001].
      CONCLUSION: ASLND, involving expensive techniques, was finally less expensive
      than ALND. The length of hospital stay was the cost driver of these procedures.
      The current observational study points the heterogeneous practices for this
      validated and largely diffused technique. Several technical choices have an
      impact on the cost of ASLND, as intraoperative analysis allowing to reduce
      rehospitalization rate for secondary lymphadenectomy or preoperative
      scintigraphy, suggesting possible savings on hospital resources.

PMID- 21896544
TI  - Towards non-surgical therapy for uterine fibroids: catechol-O-methyl transferase
      inhibitor shrinks uterine fibroid lesions in the Eker rat model.
AB  - BACKGROUND: Uterine leiomyomas (fibroids) are the most common pelvic tumors in
      women. We assessed the potential therapeutic utility of Ro 41-0960, a synthetic
      catechol-O-methyl transferase inhibitor (COMTI), in the Eker rat. METHODS: We
      randomized uterine fibroid-bearing Eker rats for treatment with Ro 41-0960 (150
      mg/kg/12 h) versus vehicle for 2 and 4 weeks. The fibroids were measured by
      caliper and subjected to histological evaluation. Urinary levels of 2-hydroxy
      estrogen (E(2)), 16-hydroxy E2 and DPD (osteoporosis marker) and serum liver
      enzymes were evaluated. Expressions of Cyclin D1, proliferating cell nuclear
      antigen (PCNA), Poly [ADP-ribose] polymerase1 (PARP1), tumor suppressor gene
      (P53) and transforming growth factor (TGFbeta3) were assessed in fibroids using
      immunohistochemical analysis or RT-PCR. Apoptosis was confirmed using terminal
      deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL). RESULTS: Ro
      41-0960-treated rats exhibited fibroid volumes of 86 +/- 7% and 105 +/- 12% of
      initial burden, at 2 and 4 weeks post-treatment, respectively, significantly
      lower than control group (240 +/- 15% and 300 +/- 18%; P< 0.01). Ro 41-0960
      increased the urinary 2-hydroxy E2/16-hydroxy E(2) ratio, level of p53 mRNA and
      TUNEL positivity (P< 0.05) and decreased PARP1, PCNA and cyclin D1 proteins and
      TGFbeta3 mRNA (P< 0.05). Ro 41-0960 did not change normal tissue histology, liver
      functions or urinary DPD level. CONCLUSIONS: Ro 41-0960 (COMTI) arrested
      growth/shrunk uterine fibroids in Eker rats. This result may be related to
      modulation of estrogen-dependent genes involved in apoptosis, proliferation and
      extracellular matrix deposition via accumulation of 2-hydroxy estrogen. The
      efficacy and safety of Ro 41-0960 in rats suggest its candidacy for treatment of
      uterine fibroids.

PMID- 21896546
TI  - Uterine allotransplantation in ewes using an aortocava patch.
AB  - BACKGROUND: We investigated a novel allotransplantation model using an aortocava
      patch in ewes. METHODS AND RESULTS: We carried out 10 uterine orthotopic
      allotransplantations in ewes with end-to-side anastomosis of the aortocava donor
      patch on the left external iliac vessel recipient. The immunosuppressive protocol
      was a combination of cyclosporine (10 mg/kg/day) and mycophenolic acid (3 g/day).
      An estimation of the immunosuppressive therapy exposure was performed by
      measuring the area under the curve (AUC) of immunosuppressive plasma
      concentrations. The graft was assessed by vaginoscopy, magnetic resonance imaging
      (MRI) and second look laparotomy at 6, 8 and 10 weeks, respectively. The median
      (range) times for cold and warm ischemia were 95 min (75-130) and 91 min (55
      165), respectively. All the vascular anastomoses were patent at the end of the
      surgery. The median AUC of cyclosporine and mycophenolic acid were 1.24 mg h/l
      (0.34-3.85) and 18.40 mg h/l (3.76-42.35), respectively. Of the 10 ewes receiving
      a transplant, 6 could be assessed. Cervical biopsies showed signs of necrosis in
      all six ewes. The MRI results correlated with the macroscopic observations of the
      'second look' laparotomy. The aortocava vascular pedicles were thrombosed, adding
      to the peripheral neovascularization. Graft histology showed endometrial tissue
      in two out of six ewes. CONCLUSIONS: Mobility of the transplant within the
      pelvis, the length of the vascular pedicle and rejection can explain the high
      rate of transplant necrosis. The particular digestive anatomy and physiology of
      ruminants makes it difficult to administer an optimal immunosuppressive
      treatment. MRI appears to be a good non-invasive examination for graft
      estimation.

PMID- 21896547
TI  - Accessing fertility treatment in New Zealand: a comparison of the clinical
      priority access criteria with a prediction model for couples with unexplained
      subfertility.
AB  - BACKGROUND: In New Zealand, public funding for assisted reproductive technology
      (ART) is restricted to subfertile women who are unlikely to conceive
      spontaneously, based on clinical and social criteria known as the clinical
      priority access criteria (CPAC) score. The objective of this study was to compare
      this CPAC score with a prediction model for predicting spontaneous conception,
      developed in the Netherlands (the Hunault model). METHODS: We performed a cohort
      study and included couples with unexplained subfertility and assessed the measure
      of agreement and the performance of the CPAC score and the Hunault prediction
      score. RESULTS: Of 663 couples referred, 249 (38%) couples had unexplained
      subfertility. Of 246 women with full follow-up data, there were 143 women (58%)
      who had a live birth during the follow-up period, 65 (26%) after fertility
      treatment and 78 (32%) after natural conception. There were 100 couples (41%) who
      had a Hunault prediction score of <30%, which is the Dutch treatment threshold,
      and 36 couples (15%) who had a CPAC score of >65, which is the New Zealand
      threshold for publically funded treatment. There were 69 couples (28%) who meet
      the threshold for treatment in the Netherlands but did not meet the New Zealand
      threshold for public funding. The kappa coefficient as a measure of agreement of
      the two scores and their treatment thresholds was 0.30, suggesting a fair
      agreement. The area under the curve for the CPAC and Hunault scores were both
      0.63, but the Hunault model performed better in calibration. CONCLUSIONS: The
      CPAC score correlates fairly with the Hunault prediction score, although using
      the Hunault prediction model 26% more couples would be recommended for ART. The
      discriminative capacities of both scores were comparable, but the Hunault
      prediction score performed better in calibration. Funding models in New Zealand
      should consider treating those women with unexplained subfertility who are least
      likely to conceive spontaneously.

PMID- 21896548
TI  - Uterus autotransplantation in cynomolgus macaques: intraoperative evaluation of
      uterine blood flow using indocyanine green.
AB  - BACKGROUND: Uterus transplantation may be the only theoretical option for some
      women, for example, those with congenital uterine infertility or who have
      undergone hysterectomy. In this study, we evaluated the intra- and post-operative
      blood flow conditions of vascular anastomosed regions and the blood-perfused area
      of the transplanted uterus in a cynomolgus macaque model of uterus
      autotransplantation. METHODS: Female cynomolgus monkeys (n = 6) underwent
      surgery: the first two animals were used to study the pelvic vascular anatomy and
      the remaining four animals were used for uterus autotransplantation. We used
      indocyanine green (ICG) fluorescent angiography during surgery to assess blood
      perfusion in the vascular anastomosed region and uterine area. After surgery, the
      uterine size, presence or absence of the endometrium and blood flow rates in the
      uterine artery and vein were evaluated using Doppler ultrasonography. RESULTS;
      Uterine arterial and venous anastomoses succeeded in all four animals that
      underwent autotransplantation. Intraoperative ICG fluorescence angiography showed
      favorable blood flow in the vascular anastomosed regions and the entire uterus
      received a sufficient blood supply from a single uterine artery. Favorable blood
      flow in the uterine artery and vein immediately after surgery was shown by
      Doppler ultrasonography. Ultimately, three out of four animals died within 3
      months following surgery because of reduced feeding and loss of body strength.
      CONCLUSIONS: ICG fluorescence angiography can be used for simple evaluation of
      real-time blood flow conditions in the anastomosed uterine artery, vein and
      uterine area and can facilitate the success rate of uterus transplantation.

PMID- 21896549
TI  - The ENDOCARE questionnaire (ECQ): a valid and reliable instrument to measure the
      patient-centeredness of endometriosis care in Europe.
AB  - BACKGROUND: Endometriosis is prevalent and women need high-quality care, which
      should be patient-centered. This study aimed to develop a valid and reliable
      patient-centeredness questionnaire, based on a defined concept of patient
      centered endometriosis care (PCEC). METHODS: A literature review, focus groups
      (FGs) with patients and an expert panel defined PCEC with 10 dimensions. The
      ENDOCARE questionnaire (ECQ) was developed. FGs resulted in 43 specific
      statements covering the 10 dimensions of PCEC, for which the ECQ measured
      'importance' and 'performance'. Medical and demographic questions and an open
      question were added. The Dutch ECQ questionnaire was piloted and reciprocally
      translated into English and Italian. Patients with endometriosis from Belgium,
      The Netherlands, Italy and the UK were invited to complete the ECQ online. Item
      analysis, inter-item analysis and confirmatory and exploratory factor analyses
      (EFA) and reliability analysis were performed. The theory-driven dimensions were
      adapted. RESULTS: The ECQ was completed by 541 patients. Based on item analysis,
      five statements were deleted. Factor analysis was performed on 322 questionnaires
      (only from respondents with a partner). Insights from the data-driven EFA
      suggested adaptations of the theory-driven dimensions. The reliability statistics
      of 9/10 adapted theory-driven dimensions were satisfactory and the root mean
      square error of approximation was good. CONCLUSIONS: This study resulted in a
      valid and reliable instrument to measure PCEC. For data presentation, the adapted
      theory-driven dimensions of PCEC are preferred over the data-driven factors. The
      ECQ may serve to benchmark patient-centeredness, conduct cross-cultural European
      research and set targets for improvement.

PMID- 21896550
TI  - Quantitative expression of phospholipase C zeta, as an index to assess
      fertilization potential of a semen sample.
AB  - BACKGROUND: Failed fertilization post-ICSI has been mainly attributed to the
      sperm's inability to induce oocyte activation. Phospholipase C zeta (PLCzeta) is
      considered to be one of the factors for the induction of oocyte activation. The
      aim of this study was to quantitatively assess the expression of PLCzeta in
      globozoospermic men or those with previously low or failed fertilization in
      comparison with fertile men or those with high fertilization potential. In
      addition, the relationship between expression of PLCzeta and that of other sperm
      markers was evaluated. METHODS: Real-time PCR was carried out to evaluate
      relative expression of PLCzeta mRNA. Chromatin maturity and acrosin activity were
      assessed by CMA3 staining and a colorimetric method. RESULTS: The expression of
      PLCzeta was significantly lower in globozoospermic men (P< 0.01, n= 8) or
      individuals with previously low or failed fertilization (P< 0.01, n= 36) in
      comparison to fertile men (n= 24). In addition, a significant difference was
      observed between globozoospermic (P< 0.01) and individuals with previously low or
      failed fertilization (P= 0.003) in comparison to high fertilization individuals
      (n= 17). Expression of PLCzeta was not correlated with either chromatin maturity
      or acrosin activity. However, a significant correlation was observed between the
      percentage of fertilization and relative expression of PLCzeta (r= 0.4, P< 0.01).
      CONCLUSION: In this study, for the first time, we have shown that assessment of
      relative expression of PLCzeta may provide a useful marker for the ability of
      sperm to induce oocyte activation after ICSI.

PMID- 21896551
TI  - Tryptophan in alcoholism treatment II: inhibition of the rat liver mitochondrial
      low Km aldehyde dehydrogenase activity, elevation of blood acetaldehyde
      concentration and induction of aversion to alcohol by combined administration of
      tryptophan and benserazide.
AB  - AIMS: The aims were to provide proofs of mechanism and principle by establishing
      the ability of the amino acid L-tryptophan (Trp) combined with the kynureninase
      inhibitor benserazide (BSZ) to inhibit the liver mitochondrial low K(m) aldehyde
      dehydrogenase (ALDH) activity after administration and in vivo and to induce
      aversion to alcohol. METHODS: Trp, BSZ or both were administered to male Wistar
      rats and ALDH activity was determined both in vitro in liver homogenates and in
      vivo (by measuring acetaldehyde accumulation in blood after ethanol
      administration). Alcohol consumption was studied in an aversion model in rats and
      in alcohol-preferring C57 mice. RESULTS: Combined administration of Trp + BSZ,
      but neither compound alone, produced a strong inhibition of ALDH activity and an
      increase in blood acetaldehyde concentration after ethanol, and induced aversion
      to alcohol in rats and decreased preference in mice. Another kynureninase
      inhibitor, carbidopa, induced aversion to alcohol by itself, which was reversed
      by Trp co-administration. CONCLUSIONS: The present results establish a prior art
      for the use of a combination of Trp plus BSZ in the treatment of alcoholism by
      aversion, which merits rapid clinical development.

PMID- 21896552
TI  - Tryptophan in alcoholism treatment I: kynurenine metabolites inhibit the rat
      liver mitochondrial low Km aldehyde dehydrogenase activity, elevate blood
      acetaldehyde concentration and induce aversion to alcohol.
AB  - AIMS: The aims were to provide proofs of mechanism and principle by establishing
      the ability of kynurenine metabolites to inhibit the liver mitochondrial low K(m)
      aldehyde dehydrogenase (ALDH) activity after administration and in vivo, and to
      induce aversion to alcohol. METHODS: Kynurenic acid (KA), 3-hydroxykynurenine (3
      HK) and 3-hydroxyanthranilic acid (3-HAA) were administered to normal male Wistar
      rats and ALDH activity was determined both in vitro in liver homogenates and in
      vivo (by measuring blood acetaldehyde following ethanol administration). Alcohol
      consumption was studied in an aversion model in rats and in alcohol-preferring
      C57 mice. RESULTS: ALDH activity was significantly inhibited by all three
      metabolites by doses as small as 1 mg/kg body wt. Blood acetaldehyde accumulation
      after ethanol administration was strongly elevated by KA and 3-HK and to a lesser
      extent by 3-HAA. All three metabolites induced aversion to alcohol in rats and
      decreased alcohol preference in mice. CONCLUSIONS: The above kynurenine
      metabolites of tryptophan induce aversion to alcohol by inhibiting ALDH activity.
      An intellectual property covering the use of 3-HK and 3-HAA and derivatives
      thereof in the treatment of alcoholism by aversion awaits further development.

PMID- 21896553
TI  - Estimation of annual effective dose due to natural and man-made radionuclides in
      the metropolitan area of the Bay of Cadiz (SW of Spain).
AB  - In order to investigate the radiological hazard of naturally occurring
      radioactive material (NORM) and man-made (137)Cs radionuclide in the Bay of
      Cadiz, 149 samples of sediments have been analysed. Activity concentration in all
      the samples was determined using a HPGe detection system. Activity concentrations
      values of (226)Ra, (232)Th, (40)K and (137)Cs in the samples were 12.6+/-2.6 (2.5
      40.6), 18.5+/-4.0 (2.8-73.4), 451+/-45 (105-1342) and 3.2+/-1.3 (0.2-16.0) Bq kg(
      1), respectively. Outdoor external dose rate due to natural and man-made
      radionuclides was calculated to be 35.79+/-1.69 (4.71-119.16) nGy h(-1) and
      annual effective dose was estimated to be 43.89+/-2.27 (5.78-146.14) uSv y(-1).
      Results showed low levels of radioactivity due to NORM and man-made (137)Cs
      radionuclide in marine sediments recovered from the Bay of Cadiz (Spain),
      discarding any significant radiological risks related to human activities of the
      area. Furthermore, the obtained data set could be used as background levels for
      future research.

PMID- 21896554
TI  - Phase II and pharmacogenomics study of enzastaurin plus temozolomide during and
      following radiation therapy in patients with newly diagnosed glioblastoma
      multiforme and gliosarcoma.
AB  - This open-label, single-arm, phase II study combined enzastaurin with
      temozolomide plus radiation therapy (RT) to treat glioblastoma multiforme (GBM)
      and gliosarcoma. Adults with newly diagnosed disease and Karnofsky performance
      status (KPS) >= 60 were enrolled. Treatment was started within 5 weeks after
      surgical diagnosis. RT consisted of 60 Gy over 6 weeks. Temozolomide was given at
      75 mg/m(2) daily during RT and then adjuvantly at 200 mg/m(2) daily for 5 days,
      followed by a 23-day break. Enzastaurin was given once daily during RT and in the
      adjuvant period at 250 mg/day. Cycles were 28 days. The primary end point was
      overall survival (OS). Progression-free survival (PFS), toxicity, and
      correlations between efficacy and molecular markers analyzed from tumor tissue
      samples were also evaluated. A prospectively planned analysis compared OS and PFS
      of the current trial with outcomes from 3 historical phase II trials that
      combined novel agents with temozolomide plus RT in patients with GBM or
      gliosarcoma. Sixty-six patients were enrolled. The treatment regimen was well
      tolerated. OS (median, 74 weeks) and PFS (median, 36 weeks) results from the
      current trial were comparable to those from a prior phase II study using
      erlotinib and were significantly better than those from 2 other previous studies
      that used thalidomide or cis-retinoic acid, all in combination with temozolomide
      plus RT. A positive correlation between O-6-methylguanine-DNA methyltransferase
      promoter methylation and OS was observed. Adjusting for age and KPS, no other
      biomarker was associated with survival outcome. Correlation of relevant
      biomarkers with OS may be useful in future trials.

PMID- 21896555
TI  - Incidence rates of fragility hip fracture in middle-aged and elderly men and
      women in southern Norway.
AB  - BACKGROUND: Hip fracture contributes to increased morbidity and mortality in the
      elderly population. As the average age of the population is increasing, the
      burden of hip fracture on the health-care system is a growing challenge. The
      highest incidence of hip fracture worldwide has been reported from Scandinavia in
      fact from Oslo the capital of Norway. During the last decades, efforts have been
      undertaken to reduce hip fracture risk. OBJECTIVE: To study the incidence of
      fragility hip fracture in southern Norway. DESIGN: A validated retrospective
      epidemiological study. SETTING: Population-based study. SUBJECTS: All patients
      with fragility hip fractures aged 50 years or older in 2004 and 2005 in southern
      Norway. METHODS: The hip fracture patients were identified from the four
      hospitals (Kristiansand, Arendal, Flekkefjord and Mandal) located in the two most
      southern counties in Norway, Vest-Agder and Aust-Agder County. Age-adjusted and
      age-specific incidence rates for men and women were calculated. We also explored
      for seasonal variations and differences between rural and urban areas. RESULTS: A
      total of 951 (271 men, 680 women) individuals aged >=50 years with hip fracture
      were identified. The age-adjusted incidence rate was 34.6 for men and 75.8 for
      women per 10,000 person-years. Age specific incidence rates were significantly
      higher in women than in men but only for age groups between 70 and 90 years.
      CONCLUSION: Age-adjusted incidence of hip fracture in men and women in southern
      Norway is the lowest reported from Norway and among the lowest in Scandinavia. No
      differences were seen between rural and urban areas. The number of fragility hip
      fractures was statistically significant higher in winter compared with the other
      seasons.

PMID- 21896556
TI  - The meaning of reporting forgetfulness: a cross-sectional study of adults in the
      English 2007 Adult Psychiatric Morbidity Survey.
AB  - OBJECTIVES: we measured subjective memory impairment (SMI) across the whole adult
      age range in a representative, national survey. Age is the strongest risk factor
      for dementia and SMI may be a precursor of objective cognitive impairment. We
      therefore hypothesised that SMI prevalence would rise with age in a non-demented
      population. METHOD: we analysed data from the English 2007 Adult Psychiatric
      Morbidity Survey, representative of people in private households. Participants
      were asked whether they had noticed problems with forgetting in the last month,
      or forgotten anything important in the last week; and completed the modified
      Telephone Interview for Cognitive Status. RESULTS: of those contacted, 7,461
      (57%) participated. After excluding participants screening positive for dementia,
      2,168 (31.7%) reported forgetfulness in the last month, while 449 (6.4%) had
      forgotten something important in the last week. Reporting forgetfulness was not
      associated with age. In a multivariate analysis including cognition and age, the
      only significant associates of reporting forgetfulness were anxiety, depressive
      and somatic symptoms. CONCLUSIONS: our hypothesis that subjective forgetfulness
      prevalence would rise with age in a non-demented population was not supported.
      Although subjective forgetfulness can be an early symptom of future or mild
      dementia, it is common and non-specific and-at population level-is more likely to
      be related to mood than to be an early symptom of dementia. Asking those
      presenting with subjective forgetfulness additional questions about memory and
      functional decline and objective forgetfulness is likely to help clinicians to
      detect those at risk of dementia.

PMID- 21896557
TI  - Wearing hip protectors does not reduce health-related quality of life in older
      people.

PMID- 21896558
TI  - Goal setting as a feature of homecare services for older people: does it make a
      difference?
AB  - INTRODUCTION: Health services delivered in an older person's home are often
      implemented at a critical juncture in an individual's functional status. Although
      homecare has potential to improve this situation, it often focuses on treating
      disease and 'taking care' of the patient rather than promoting independence. The
      aim of restorative homecare is to change the philosophy from one where delivery
      of care may create dependency to provision of care which maximises independence,
      self-esteem, self-image and quality of life, and reduces the care required. AIMS:
      To assess impact of a designated goal facilitation tool on health-related quality
      of life (HRQoL), social support and physical function among community-dwelling
      older people referred for homecare. METHODS: A total of 205 participants [mean
      age 79.1 years, 71.3% female (intervention group) and 76.9 years with 60.8%
      female (control group)] were cluster randomised to an intervention or control
      assessor. The intervention arm involved participants completing a goal
      facilitation tool with assessors. This established rehabilitation aims. Control
      participants received a standard needs assessment. Clients from both groups were
      then referred to a homecare organisation for service delivery. RESULTS: There was
      greater change over time in HRQoL [measured by Short Form 36 Survey (SF-36)] in
      the intervention group (P = 0.0001). There was a marked variation across homecare
      providers in types of services provided (P < 0.001). Identification of a goal did
      not predict completion of a formalised review of participants' needs by the
      homecare organisation. CONCLUSIONS: Use of a goal facilitation tool in assessment
      of an older person's needs on referral for homecare leads to significant
      improvements in HRQoL. This may be through a higher proportion of individualised
      activities tailored to a successful identification of the person's goals. The
      findings contribute to greater understanding of factors necessary to implement
      improvements in homecare services for older people.

PMID- 21896559
TI  - Long-term endocrine side effects of childhood Hodgkin's lymphoma treatment: a
      review.
AB  - BACKGROUND Since childhood cancer survival has increased, long-term effects of
      treatment have gained interest. Childhood Hodgkin's lymphoma has been treated
      successfully for decades now. We provide an overview of the literature on long
      term endocrine side effects, such as gonadal dysfunction and growth retardation,
      as a result of childhood Hodgkin's lymphoma treatment.  METHODS A comprehensive
      search of the Pubmed database was performed.  RESULTS We identified 16 studies
      (10 studies: 298 male survivors and 6 studies: 230 female survivors) about
      gonadal dysfunction. In survivors treated with alkylating agents or pelvic
      radiotherapy, severe gonadal damage is described. Recovery was rarely described.
      Seven studies (481 survivors) about bone mineral density (BMD) and growth were
      identified. The effects on BMD appear to be small. Data on growth are scarce, but
      show that radiotherapy in a dose of >30 Gy including the spine, especially in pre
      pubertal children, results in reduced height. We included 10 studies (4012
      survivors) about thyroid complications. Hypothyroidism is the most common thyroid
      disorder after radiotherapy. There is also a significant incidence in thyroid
      carcinoma after low-dose radiation. In survivors treated with chemotherapy only,
      hypothyroidism and thyroid cancer have not been reported.  CONCLUSIONS The
      severity of endocrine toxicity after childhood Hodgkin's lymphoma depends on the
      type of treatment. Gonadal dysfunction seems to be the most severe endocrine long
      term effect, especially after treatment with alkylating agents or pelvic
      radiotherapy. The knowledge obtained in specific follow-up programmes for
      paediatric cancer survivors will help to find the optimal balance between
      curability and long-term side effects.

PMID- 21896562
TI  - The early clinical x-ray in the United States: patient experiences and public
      perceptions.
AB  - The first x-ray machines were large, loud, sparking, smelly, and ostentatious
      devices, prone to mishap and injury even when fully under the control of the
      physicians who, in droves, invested money and prestige in them. Their bizarre and
      sometimes overwhelming presentation in the clinic reinforced the contemporary
      public understanding of x-rays as fantastically potent yet ambiguously helpful.
      As one of the icons of the new scientific medicine, x-rays bore much of the
      public's expectations for a technological panacea, a belief that was reinforced
      by the spectacle of their generation and their undeniable effect on the body. A
      quarter century later, refinement of the technology had made irradiation safer
      and more effective, but also made the operation of the machines themselves almost
      undetectable. This "domestication" of x-ray machines underscored their failure as
      a modern-day heroic medicine, while reinforcing an emergent understanding of
      radiation as a subtle, cumulative, and insidious threat.

PMID- 21896563
TI  - Takayasu's arteritis involving the pulmonary arteries: evaluation by quantitative
      dual-energy computed tomographic pulmonary angiography.

PMID- 21896561
TI  - A randomized trial of the efficacy and safety of sequential intravenous/oral
      moxifloxacin monotherapy versus intravenous piperacillin/tazobactam followed by
      oral amoxicillin/clavulanate for complicated skin and skin structure infections.
AB  - OBJECTIVES: The primary aim of the RELIEF study was to evaluate the efficacy and
      safety of two sequential intravenous (iv)/oral regimens: moxifloxacin iv/oral
      versus piperacillin/tazobactam (TZP) iv followed by oral amoxicillin/clavulanate
      (AMC). PATIENTS AND METHODS: The study had a prospective, randomized, double
      dummy, double-blind, multicentre design. Patients >=18 years were prospectively
      stratified according to complicated skin and skin structure infection (cSSSI)
      subtype/diagnosis (major abscess, diabetic foot infection, wound infection or
      infected ischaemic ulcer), surgical intervention and severity of illness.
      Diagnoses and disease severity were based on predetermined criteria, documented
      by repeated photographs, and confirmed by an independent data review committee.
      Patients were randomized to receive either 400 mg of moxifloxacin iv once daily
      followed by 400 mg of moxifloxacin orally once daily or 4.0/0.5 g of TZP iv
      thrice daily followed by 875/125 mg of AMC orally twice daily for 7-21 days. The
      primary efficacy variable was clinical response at test of cure (TOC) for the per
      protocol (PP) population. Clinical efficacy was assessed by the data review
      committee based on repeated photographs and case descriptions. Clinical trials
      registry number: NCT 00402727. RESULTS: A total of 813 patients were randomized.
      Clinical success rates at TOC were similar for moxifloxacin and TZP-AMC in the PP
      [320/361 (88.6%) versus 275/307 (89.6%), respectively; P = 0.758] and intent-to
      treat (ITT) [350/426 (82.2%) versus 305/377 (80.9%), respectively; P = 0.632]
      populations. Thus, moxifloxacin was non-inferior to TZP-AMC. Bacteriological
      success rates were high in both treatment arms [moxifloxacin: 432/497 (86.9%)
      versus TZP-AMC: 370/429 (86.2%), microbiologically valid (MBV) population].
      Moxifloxacin was non-inferior to TZP-AMC at TOC in both the MBV and the ITT
      populations. Both treatments were well tolerated. CONCLUSIONS: Once-daily iv/oral
      moxifloxacin monotherapy was clinically and bacteriologically non-inferior to iv
      TZP thrice daily followed by oral AMC twice daily in patients with cSSSIs.

PMID- 21896560
TI  - Contemporary genetic technologies and female reproduction.
AB  - BACKGROUND: The Fifth Evian Annual Reproduction (EVAR) Workshop Meeting discussed
      knowledge regarding contemporary genetics in female reproduction. METHODS:
      Specialist reproductive medicine clinicians and geneticists delivered
      presentations based on published literature and current research. The content of
      this report is based on the expert presentations and subsequent group discussions
      that took place during this Workshop. RESULTS: Numerous ovarian genes with a role
      in infertility have been identified. Future challenges for genetic screening of
      patients, such as those with polycystic ovary syndrome, primary ovarian
      insufficiency or endometriosis, include the identification of high-throughput
      strategies and how to apply these findings to infertile patients. The
      identification of high-quality embryos in IVF using objective technologies
      remains a high priority in order to facilitate single-embryo transfer. Gene
      expression profiling of cumulus cells surrounding the oocyte, and proteomic and
      metabolomic approaches in embryo culture media may significantly improve non
      invasive embryo quality assessment. CONCLUSIONS: The way forward in advancing the
      knowledge of genes involved in reproduction was considered to be through genome
      wide association studies involving large numbers of patients. Establishing
      international collaboration is required to enable the application of such
      technologies in sufficient numbers of patients.

PMID- 21896564
TI  - Creating controversy where none exists: the important role of C-reactive protein
      in the CARE, AFCAPS/TexCAPS, PROVE IT, REVERSAL, A to Z, JUPITER, HEART
      PROTECTION, and ASCOT trials.

PMID- 21896565
TI  - Comparative evaluation of three commercially available complement fixation test
      antigens for the diagnosis of glanders.
AB  - The sensitivity and specificity of three commercially available complement
      fixation test (CFT) antigens from c.c.pro (c.c.pro), Central Veterinary Institute
      of Wageningen UR (CIDC) and the United States Department of Agriculture (USDA)
      were comparatively evaluated by testing 410 sera collected from glanders-endemic
      and non-endemic areas (200 true-negative randomly collected sera and 210 sera
      collected from experimentally immunised animals (12 rabbits, 19 horses),
      clinically positive (135) and culture-positive (44) horses, donkeys and mules).
      Immunoblotting (IB) was used as the gold standard test. Highest sensitivity was
      shown for the CIDC antigen (100 per cent) followed by the c.c.pro antigen (99.39
      per cent). However, the USDA antigen showed substantially less (p<0.05)
      sensitivity (62.19 per cent). Highest specificity was found for the USDA antigen
      (100 per cent) followed by the CIDC (97.5 per cent) and c.c.pro antigen (96.5 per
      cent). Positive and negative predictive values (assumed glanders prevalence of
      <0.1 per cent) for each antigen were calculated to be 95.88 and 99.48 (c.c.pro),
      97.04 and 100 (CIDC), 100 and 76.33 per cent (USDA), respectively. Almost perfect
      agreement (0.96) was found between CFT using either c.c.pro or CIDC and IB.

PMID- 21896566
TI  - Comparison of xylazine-butorphanol and xylazine-morphine-ketamine infusions in
      horses undergoing a standing surgery.

PMID- 21896567
TI  - Canine breeds at high risk of developing inflammatory bowel disease in the south
      eastern UK.
AB  - Genetics are an important factor in the development of human inflammatory bowel
      disease (IBD); however, there is very little information available regarding the
      role of genetics in canine IBD. The purpose of this study was to gather
      information about which canine breeds in the south-eastern UK are at a high risk
      for developing IBD. Determination of such breeds may help further genetic
      research in this complex disease. The computer medical records at the Queen
      Mother Hospital for Animals, Royal Veterinary College dating from August 1, 2003
      to December 31, 2009 were retrospectively searched for cases diagnosed with IBD.
      Five hundred and forty-six dogs with IBD were identified, representing 86
      different breeds. The comparison group consisted of all dogs from these same 86
      breeds without IBD admitted to the hospital during the same period that amounted
      to 27,463 dogs. The breeds at significantly higher risk of developing IBD
      compared with mixed-breed dogs consisted of weimaraner (odds ratio [OR]=3.6797,
      95 per cent confidence interval [CI]=2.0167 to 6.7141, P<0.0001), rottweiler
      (OR=2.9697, 95 per cent CI=1.7569 to 5.0196, P<0.0001), German shepherd dog (GSD)
      (OR=2.4101, 95 per cent CI=1.5826 to 3.36705, P<0.0001), border collie
      (OR=1.9936, 95 per cent CI=1.1655 to 3.4101, P=0.0118) and boxer (OR=1.6961, 95
      per cent CI=1.0441 to 2.755, P=0.0328). This study demonstrates for the first
      time canine breeds in the south-eastern UK that are highly susceptible to
      developing IBD. Identification of such breeds may allow for a more focused
      investigation of genetic mutations associated with canine IBD.

PMID- 21896568
TI  - Reliability of ultrasonography at the fifth intercostal space in the diagnosis of
      reticular diaphragmatic hernia.

PMID- 21896569
TI  - Purification and characterization of the acetyl-CoA synthetase from Mycobacterium
      tuberculosis.
AB  - Acetyl-CoA (AcCoA) synthetase (Acs) catalyzes the conversion of acetate into
      AcCoA, which is involved in many catabolic and anabolic pathways. Although this
      enzyme has been studied for many years in many organisms, the properties of
      Mycobacterium tuberculosis Acs and the regulation of its activity remain unknown.
      Here, the putative acs gene of M. tuberculosis H37Rv (Mt-Acs) was expressed as a
      fusion protein with 6*His-tag on the C-terminus in Escherichia coli. The
      recombinant Mt-Acs protein was successfully purified and then its enzymatic
      characteristics were analyzed. The optimal pH and temperature, and the kinetic
      parameters of Mt-Acs were determined. To investigate whether Mt-Acs is regulated
      by lysine acetylation as reported for Salmonella enterica Acs, its mutant K617R
      was also generated. Determination of the enzymatic activity suggests that Lys-617
      is critical for its function. We further demonstrated that Mt-Acs underwent auto
      acetylation with acetate but not with AcCoA as the acetyl donor, which resulted
      in the decrease of its activity. CoA, the substrate for AcCoA formation,
      inhibited the auto-acetylation. Furthermore, the silent information regulator
      (Sir2) of M. tuberculosis (Mt-Sir2) could catalyze Mt-Acs deacetylation, which
      resulted in activation of Acs. These results may provide more insights into the
      physiological roles of Mt-Acs in M. tuberculosis central metabolism.

PMID- 21896570
TI  - Sesamin induces melanogenesis by microphthalmia-associated transcription factor
      and tyrosinase up-regulation via cAMP signaling pathway.
AB  - In this study, we confirmed that sesamin, an active lignan isolated from sesame
      seed and oil, is a novel skin-tanning compound. The melanin content and
      tyrosinase activity were increased by sesamin in a dose-dependent manner in B16
      melanoma cells. The mRNA and protein levels of tyrosinase were also enhanced
      after the treatment with sesamin. Western blot analysis revealed that sesamin
      induced and sustained up-regulation of microphthalmia-associated transcription
      factor (MITF). Sesamin could activate cAMP response element (CRE) binding protein
      (CREB), but it had no effect on the phosphorylation of p38 mitogen-activated
      protein kinase (MAPK) or Akt. Moreover, sesamin activated protein kinase A (PKA)
      via a cAMP-dependent pathway. Consistent with these results, sesamin-mediated
      increase of melanin synthesis was reduced significantly by H-89, a PKA inhibitor,
      but not by SB203580, a p38 MAPK inhibitor or by LY294002, a phosphatidylinositol
      3-kinase (PI3K) inhibitor. Sesamin-mediated phosphorylation of CREB and induction
      of MITF and tyrosinase expression were also inhibited by H-89. These findings
      indicated that sesamin could stimulate melanogenesis in B16 cells via the up
      regulation of MITF and tyrosinase, which was, in turn, due to the activation of
      cAMP signaling.

PMID- 21896571
TI  - Histone octamer trans-transfer: a signature mechanism of ATP-dependent chromatin
      remodelling unravelled in wheat nuclear extract.
AB  - BACKGROUND AND SCOPE: In eukaryotes, chromatin remodelling complexes are shown to
      be responsible for nucleosome mobility, leading to increased accessibility of DNA
      for DNA binding proteins. Although the existence of such complexes in plants has
      been surmised mainly at the genetic level from bioinformatics studies and
      analysis of mutants, the biochemical existence of such complexes has remained
      unexplored. METHODS: Histone H1-depleted donor chromatin was prepared by
      micrococcal nuclease digestion of wheat nuclei and fractionation by exclusion
      chromatography. Nuclear extract was partially purified by cellulose phosphate ion
      exchange chromatography. Histone octamer trans-transfer activity was analysed
      using the synthetic nucleosome positioning sequence in the absence and presence
      of ATP and its analogues. ATPase activity was measured as (32)Pi released using
      liquid scintillation counting. KEY RESULTS: ATP-dependent histone octamer trans
      transfer activity, partially purified from wheat nuclei using cellulose
      phosphate, showed ATP-dependent octamer displacement in trans from the H1
      depleted native donor chromatin of wheat to the labelled synthetic nucleosome
      positioning sequence. It also showed nucleosome-dependent ATPase activity.
      Substitution of ATP by ATP analogues, namely ATPgammaS, AMP-PNP and ADP abolished
      the octamer trans-transfer, indicating the requirement of ATP hydrolysis for this
      activity. CONCLUSIONS: ATP-dependent histone octamer transfer in trans is a
      recognized activity of chromatin remodelling complexes required for chromatin
      structure dynamics in non-plant species. Our results suggested that wheat nuclei
      also possess a typical chromatin remodelling activity, similar to that in other
      eukaryotes. This is the first report on chromatin remodelling activity in vitro
      from plants.

PMID- 21896572
TI  - Optimizing nitrogen economy under drought: increased leaf nitrogen is an
      acclimation to water stress in willow (Salix spp.).
AB  - BACKGROUND AND AIMS: The major objective was to identify plant traits
      functionally important for optimization of shoot growth and nitrogen (N) economy
      under drought. Although increased leaf N content (area basis) has been observed
      in dry environments and theory predicts increased leaf N to be an acclimation to
      drought, experimental evidence for the prediction is rare. METHODS: A pedigree of
      200 full-sibling hybrid willows was pot-grown in a glasshouse in three replicate
      blocks and exposed to two water regimes for 3 weeks. Drought conditions were
      simulated as repeated periods of water shortage. The total leaf mass and area,
      leaf area efficiency (shoot growth per unit leaf area, E(A)), area-based leaf N
      content (N(A)), total leaf N pool (N(L)) and leaf N efficiency (shoot growth per
      unit leaf N, E(N)) were assessed. KEY RESULTS: In the water-stress treatment,
      shoot biomass growth was N limited in the genotypes with low N(L), but
      increasingly limited by other factors in the genotypes with greatest N(L). The
      N(A) was increased by drought, and drought-induced shift in N(A) varied between
      genotypes (significant G * E). Judged from the E(A)-N(A) relationship, optimal
      N(A) was 16 % higher in the water-stress compared with the well-watered
      treatment. Biomass allocation to leaves and shoots varied between treatments, but
      the treatment response of the leaf : shoot ratio was similar across all
      genotypes. CONCLUSIONS: It is concluded that N-uptake efficiency and leaf N
      efficiency are important traits to improve growth under drought. Increased leaf N
      content (area basis) is an acclimation to optimize N economy under drought. The
      leaf N content is an interesting trait for breeding of willow bioenergy crops in
      a climate change future. In contrast, leaf biomass allocation is a less
      interesting breeding target to improve yield under drought.

PMID- 21896573
TI  - Effects of light quality on leaf morphogenesis of a heterophyllous amphibious
      plant, Rotala hippuris.
AB  - BACKGROUND AND AIMS: For heterophyllous amphibious plants that experience
      fluctuating water levels, it is critical to control leaf development precisely in
      response to environmental cues that can serve as a quantitative index of water
      depth. Light quality can serve as such a cue because the ratio of red light
      relative to far-red light (R/FR) increases and blue-light intensity decreases
      with increasing water depth. Growth experiments were conducted to examine how
      R/FR and blue-light intensity alter leaf morphology of a heterophyllous
      amphibious plant, Rotala hippuris. METHODS: Using combinations of far red (730
      nm), red (660 nm) and blue (470 nm) light-emitting diodes (LEDs), growth
      experiments were used to quantitatively evaluate the effects of the R/FR ratio
      and blue-light intensity on leaf morphology. KEY RESULTS: Under the natural light
      regime in an outside growth garden, R. hippuris produced distinct leaves under
      submerged and aerial conditions. R/FR and blue-light intensity were found to
      markedly affect heterophyllous leaf formation. Higher and lower R/FR caused leaf
      characters more typical of submerged and aerial leaves, respectively, in both
      aerial and submerged conditions, in accordance with natural distribution of leaf
      types and light under water. High blue light caused a shift of trait values
      toward those of typical aerial leaves, and the response was most prominent under
      conditions of R/FR that were expected near the water surface. CONCLUSIONS: R/FR
      and blue-light intensity provides quantitative cues for R. hippuris to detect
      water depth and determine the developmental fates of leaves, especially near the
      water surface. The utilization of these quantitative cues is expected to be
      important in habitats where plants experience water-level fluctuation.

PMID- 21896574
TI  - Absent pulmonary valve syndrome: prenatal cardiac ultrasound diagnosis with
      autopsy correlation.
AB  - Absent pulmonary valve syndrome (APVS) is a rare conotruncal anomaly consisting
      of a severely hypoplastic pulmonary valve with annular stenosis, aneurysmal
      dilatation of main pulmonary artery with dilatation of one or both pulmonary
      artery branches, and a ventricular septal defect. Here, we report a prenatal echo
      diagnosis of APVS in a 27-year-old primi gravida at 20 weeks of gestation
      confirmed on fetal autopsy. A 'bow tie'-like hypoechoic shadow in fetal cardiac
      ultrasound observed by us in a modified four-chamber view was suggestive of
      aneurysmal dilatation of branch pulmonary arteries. The consequences of
      continuation of pregnancy including immediate neonatal complications and possible
      medical and multistaged surgical interventions were well explained. Parents opted
      for medical termination of pregnancy. Autopsy findings of the fetus were
      consistent with the prenatal echo diagnosis of APVS. The presence of patent
      ductus arteriosus seen in the autopsy may be the cause of severe heart failure
      evidenced by the abnormally large congested liver, dilated right heart chambers,
      and tricuspid valve annulus. We infer that the prenatal diagnosis of APVS may be
      possible with a high degree of accuracy with characteristic fetal
      echocradiographic findings such as 'bow tie'-like or 'ballooning'-like shadows
      observed in this case. The presence of ductus confirms definite fetal loss and
      the parents can be counselled accordingly. However, when the ductus is absent,
      decision-making is difficult as the fetus is going to survive.

PMID- 21896575
TI  - Why play an active role? A qualitative examination of lay citizens' main motives
      for participation in health promotion.
AB  - While active participation is regarded essential in health promotion worldwide,
      its application proves to be challenging. Notably, participants' experiences are
      infrequently studied, and it is largely unknown why lay citizens would want to
      play an active role in promoting the health of the community they belong to.
      Aiming to produce practical insights to further the application of the
      participation principle, this qualitative study examined participants' driving
      motives in a diverse array of health promotion undertakings. Six projects in The
      Netherlands were used as case studies, including a community-project promoting
      mental health, peer education against harmful substance use, a health support
      group, health policy development, physical activity and healthy life style
      courses. The study involved 24 participants, who played a variety of active
      roles. Semi-structured interviews were conducted, transcribed verbatim and
      subjected to content analysis. We found four main motives driving lay citizens in
      their active participation in health promotion projects: 'purposeful action',
      'personal development', 'exemplary status' and 'service and reciprocity'. The
      motives reflected crucially distinct personal desires in the participation
      process, namely to produce tangible results, to experience advancements for
      oneself, to gain personal recognition as a role model and to have or maintain
      valued relationships. The implications of the findings are discussed for
      researchers and professionals in health promotion.

PMID- 21896576
TI  - Tandem mass spectrometry findings at autopsy for detection of metabolic disease
      in infant deaths: postmortem changes and confounding factors.
AB  - AIM: Tandem mass spectrometry (MS/MS) is a recommended investigation for sudden
      unexpected death in infancy (SUDI), but there are limited data regarding yield
      and potential influencing factors. This study investigates postmortem
      acylcarnitine profiles in a large cohort of infant deaths from a single centre,
      including those with metabolic disease. METHODS: Acylcarnitine results obtained
      by MS/MS from routine blood/bile spot samples during the standard autopsy
      investigation were identified from infant deaths over a 14-year period. Results
      were categorised as normal or abnormal according to the clinical report by a
      specialist paediatric biochemist. Possible interdependent variables were
      assessed, multiple linear regression models were constructed and residual
      comparison was undertaken. RESULTS: 397 blood and 268 bile MS/MS results were
      identified from infant cases, including 255 matched blood-bile pairs. There was
      significant association between blood acylcarnitine findings and postmortem
      interval (PMI), body mass index and liver weight. A probable cause of death was
      identified in 40% of sudden death cases, including 18 (2%) with a definite or
      highly likely cause of death as underlying metabolic disease; this represented 12
      (12%) unexpected deaths in the first week of life and six (<1%) aged 7-365 days.
      Fatty acid oxidation disorders identified included very long chain acyl-CoA
      dehydrogenase deficiency, medium chain acyl-CoA dehydrogenase deficiency and
      carnitine transporter defects. CONCLUSION: Postmortem blood and bile
      acylcarnitine profiles are influenced by several variables, and PMI can influence
      MS/MS acylcarnitine results. Metabolic disease may present as SUDI and may be
      identified from postmortem samples.

PMID- 21896577
TI  - The pathogenesis, diagnosis, investigation and management of osteoporosis.
AB  - With an increasingly ageing population, osteoporosis and osteoporosis-related
      fractures is fast becoming an important public health problem placing a
      considerable economic burden on health service resources. This does not account
      for the substantial pain, disability and indeed mortality incurred after a
      fracture, particularly a hip fracture. Osteoporosis is a systemic skeletal
      disorder which results from an imbalance in bone remodeling. This leads to a
      reduction in bone strength and increased susceptibility to fracture. It affects
      up to 1 in 2 women and 1 in 5 men. In the past 2 decades, there have been
      significant advances in bone biology which have helped in the understanding of
      the pathogenesis of osteoporosis and have led to improved therapies. In
      developing strategies for fracture prevention, it is important to identify those
      individuals with the highest fracture risk who will require pharmacological
      intervention. Treatment is aimed at fracture prevention and includes modification
      of general lifestyle factors which have been linked to fractures in
      epidemiological studies and ensuring optimum calcium and vitamin D intake as
      adjunct to active anti-fracture therapy. A number of drugs are now approved for
      the treatment of osteoporosis. This review article will describe the pathogenesis
      of osteoporosis and focus on the methods currently in use for the identification
      of patients at high fracture risk and will highlight their usefulness and
      limitations. The existing anti-fracture pharmacotherapies and those in
      development will be reviewed. Assessment of their effectiveness including the use
      of biochemical markers of bone turnover in this clinical context will be
      reviewed.

PMID- 21896578
TI  - Dual-colour HER2/chromosome 17 chromogenic in situ hybridisation enables accurate
      assessment of HER2 genomic status in ovarian tumours.
AB  - BACKGROUND: Ovarian cancer is a leading cause of gynaecological cancer-related
      morbidity and mortality. There has been increasing interest in the potential
      utility of anti-human epidermal growth factor receptor 2 (anti-HER2) agents in
      the treatment of this disease, with the attendant need to identify suitable
      predictive biomarkers of response to treatment. AIMS/METHODS: The authors studied
      the prevalence of HER2 genomic amplification and overexpression in 85 ovarian
      tumours in the local patient cohort of this study, as well as the concordance
      rate between immunohistochemistry, fluorescent in situ hybridisation (FISH) and a
      dual-colour HER2/chromosome 17 centromere chromogenic in situ hybridisation
      (CISH) assay. RESULTS: The authors identified HER2 genomic amplification and
      protein overexpression in 35.3% (6/17) and 29.4% (5/17), respectively, of primary
      ovarian mucinous carcinomas. No other cancer subtypes displayed HER2
      amplification or protein overexpression. The authors also found a perfect
      concordance between FISH and dual-colour CISH analysis (kappa coefficient 1.0,
      p<0.001). CONCLUSION: The results of this study support existing reports that
      HER2 genomic amplification and protein overexpression are predominantly found in
      primary ovarian mucinous carcinomas. Given the perfect concordance between the
      FISH and dual-colour CISH assays and the advantages of CISH over FISH analysis,
      future clinical trials investigating the use of anti-HER2 therapeutics in ovarian
      carcinomas should incorporate dual-colour CISH as part of the HER2 status
      assessment algorithm.

PMID- 21896579
TI  - Assessment of proliferation markers in metastatic melanoma in sentinel lymph
      nodes.
AB  - AIM: Some views on sentinel nodes for melanoma seem to cast doubt on the
      relevance of micrometastases in the sentinel nodes of patients with melanoma,
      suggesting that small metastases or isolated tumour cells can be ignored. Tumour
      dormancy has been proposed for their postulated lack of progression. The
      implication of the argument seems to be that minute metastases are inactive and
      therefore non-threatening, whereas larger ones are proliferative and therefore
      have aggressive potential. METHODS: 54 sentinel lymph nodes were studied with
      histologically identified micrometastatic melanoma using the protocol accepted by
      the European Organisation for Research and Treatment of Cancer melanoma group.
      These were studied with respect to metastasis size and by use of
      immunohistochemical markers of proliferation (MIB-1) and dormancy (p16). RESULTS:
      The authors have demonstrated no correlation between the size of metastases and
      their proliferative activity. Very small metastases may not show proliferative
      activity, but this may be a reflection of the small number of assessable cells
      rather than a genuine reflection of the tumoural characteristics. Furthermore,
      the minute size of some of these metastases resulted in no residual tumour being
      present in adjacent sections. Where further sections did show more tumour, these
      small metastases were invariably p16 negative, suggesting dormancy was not the
      explanation for the lack of measurable proliferation. Occasionally, larger
      metastases, clearly not clinically insignificant, showed no proliferative
      activity presumably, considering their size, a transient phenomenon. CONCLUSION:
      These findings suggest that variable phases in proliferation occur in metastases,
      and no conclusion of clinical insignificance can be made on the basis of small
      size.

PMID- 21896580
TI  - Best practice in primary care pathology: review 14.
AB  - This 14th best practice review is the second of a pair that examines tumour
      marker requesting primary care situations. This review considers carbohydrate
      antigen 125, alpha-fetoprotein and human chorionic gonadotropin. It is presented
      in question-answer format, referenced for each question. The recommendations
      represent a precis of guidance found using a standardised literature search of
      national and international guidance notes, consensus statements, health policy
      documents and evidence-based medicine reviews, supplemented by MEDLINE EMBASE
      searches to identify relevant primary research documents. They will be updated
      periodically to take into account new information.

PMID- 21896581
TI  - Valve pathology: a dying trade.

PMID- 21896582
TI  - Pseudoinvasion of benign squamous epithelium following cervical biopsy: a
      pseudoneoplastic phenomenon mimicking invasive squamous carcinoma.
AB  - AIMS: To describe an unusual and hitherto unreported pseudoneoplastic phenomenon
      that is characterised by the entrapment of benign squamous epithelium following
      cervical loop excision or punch biopsy and that may mimic invasive squamous
      carcinoma. METHODS AND RESULTS: The authors report six cases in patients aged 25
      45 years in whom benign squamous epithelium is incorporated within the cervical
      stroma as a result of the healing process following prior loop excision (four
      cases) or punch biopsy (two cases). The entrapped nests of squamous epithelium
      typically have a hypereosinophilic appearance and are associated with a
      granulation tissue-like and inflammatory stromal response and sometimes with
      retraction artefact mimicking lymphovascular permeation. CONCLUSIONS: The overall
      morphological appearances, especially in the context of a prior or current
      diagnosis of cervical intraepithelial neoplasia, may result in misdiagnosis as
      invasive squamous carcinoma. Pathologists should be aware of this
      pseudoneoplastic artefact so that an erroneous diagnosis of malignancy is not
      made.

PMID- 21896583
TI  - Agencies prepare to deal with mental health problems in Libya after 42 years of
      repression.

PMID- 21896584
TI  - Trust and health department deny acting illegally over "do not resuscitate"
      order.

PMID- 21896585
TI  - London needs to reconfigure its HIV services, says Civitas report.

PMID- 21896586
TI  - Browsing the internet. Does the internet limit or extend the human mind? Probably
      both.

PMID- 21896587
TI  - Differences in brain hemispheres deserves more thoughtful approach.

PMID- 21896589
TI  - Tackling conflicts of interest. Subjective editorials and clinical reviews
      require proof of objectivity.

PMID- 21896590
TI  - Tackling conflicts of interest. Ban against industry ties introduces bias and
      obscures whole view.

PMID- 21896591
TI  - Tackling conflicts of interest. Two reasons to be cautious when considering bans
      on industry ties.

PMID- 21896592
TI  - Tackling conflicts of interest. Industry tie may be benchmark of quality.

PMID- 21896593
TI  - Tackling conflicts of interest. Collaboration with industry facilitates useful
      research that wouldn't happen otherwise.

PMID- 21896594
TI  - Tackling conflicts of interest. BMJ tackles FDA's mote in eye while ignoring own
      beam.

PMID- 21896595
TI  - Tackling conflicts of interest. Conflicts of interest and drug information.

PMID- 21896596
TI  - Curiousness of increasing obesity and longer life expectancy.

PMID- 21896597
TI  - Cardiovascular prevention may increase healthcare and other costs.

PMID- 21896598
TI  - Wrong argument?

PMID- 21896599
TI  - How did clinical circumstances change?

PMID- 21896600
TI  - US breast cancer mortality is consistent with European data.

PMID- 21896601
TI  - Tackling conflicts of interest. American Family Physician has prohibited using
      editorialists with industry ties for over 20 years.

PMID- 21896602
TI  - FDA finds breast implants to be safe but calls for better follow-up.

PMID- 21896603
TI  - Tackling conflicts of interest. What the New England Journal of Medicine did.

PMID- 21896605
TI  - Life expectancy varies across WHO Europe region by 16 years.

PMID- 21896606
TI  - Prosecutors have taken no action over cases of suspected assisted suicide since
      new guidance was issued.

PMID- 21896608
TI  - Ageing, menopause, and ischaemic heart disease mortality in England, Wales, and
      the United States: modelling study of national mortality data.
AB  - OBJECTIVES: To use changes in heart disease mortality rates with age to
      investigate the plausibility of attributing women's lower heart disease mortality
      than men to the protective effects of premenopausal sex hormones. DESIGN:
      Modelling study of longitudinal mortality data with models assuming (i) a linear
      association between mortality rates and age (absolute mortality) or (ii) a
      logarithmic association (proportional mortality). We fitted models to age and sex
      specific mortality rates in the census years 1950 to 2000 for three birth cohorts
      (1916-25, 1926-35, and 1936-45). DATA SOURCES: UK Office for National Statistics
      and the US National Center for Health Statistics. Main outcome measure(s) Fit of
      models to data for England and Wales and for the US. RESULTS: For England-Wales
      data, proportional increases in ischaemic heart disease mortality fitted the data
      better than absolute increases (improvement in deviance statistics: women, 58
      logarithmic units; men, 37). We identified a deceleration in male mortality after
      age 45 years (decreasing from 30.3% to 5.2% per age-year, P = 0.042), although
      the corresponding difference in women was non-significant (P = 0.43, overall
      trend 7.9% per age-year, P<0.001). By contrast, female breast cancer mortality
      decelerated significantly after age 45 years (decreasing from 19.3% to 2.6% per
      age-year, P<0.001). We found similar results in US data. CONCLUSIONS:
      Proportional age related changes in ischaemic heart disease mortality, suggesting
      a loss of reparative reserve, fit longitudinal mortality data from England,
      Wales, and the United States better than absolute age related changes in
      mortality. Acceleration in male heart disease mortality at younger ages could
      explain sex differences rather than any menopausal changes in women.

PMID- 21896609
TI  - Sex differences in the risk of cardiovascular disease.

PMID- 21896610
TI  - Evidence of comparative efficacy should have a formal role in European drug
      approvals.

PMID- 21896612
TI  - Adenoidectomy in children with recurrent upper respiratory infections.

PMID- 21896611
TI  - Effectiveness of adenoidectomy in children with recurrent upper respiratory tract
      infections: open randomised controlled trial.
AB  - OBJECTIVE: To assess the effectiveness of adenoidectomy in children with
      recurrent upper respiratory tract infections. DESIGN: Open randomised controlled
      trial. SETTING: 11 general hospitals and two academic centres. PARTICIPANTS: 111
      children aged 1-6 with recurrent upper respiratory tract infections selected for
      adenoidectomy. INTERVENTION: A strategy of immediate adenoidectomy with or
      without myringotomy or a strategy of initial watchful waiting. Main outcome
      measure Primary outcome measure: number of upper respiratory tract infections per
      person year calculated from data obtained during the total follow-up (maximum 24
      months). SECONDARY OUTCOME MEASURES: days with upper respiratory tract infection
      per person year, middle ear complaints with fever in episodes and days, days with
      fever, prevalence of upper respiratory tract infections, and health related
      quality of life. RESULTS: During the median follow-up of 24 months, there were
      7.91 episodes of upper respiratory tract infections per person year in the
      adenoidectomy group and 7.84 in the watchful waiting group (difference in
      incidence rate 0.07, 95% confidence interval -0.70 to 0.85). No relevant
      differences were found for days of upper respiratory tract infections and middle
      ear complaints with fever in episodes and days, nor for health related quality of
      life. The prevalence of upper respiratory tract infections decreased over time in
      both groups. Children in the adenoidectomy group had significantly more days with
      fever than the children in the watchful waiting group. Two children had
      complications related to surgery. CONCLUSION: In children selected for
      adenoidectomy for recurrent upper respiratory tract infections, a strategy of
      immediate surgery confers no clinical benefits over a strategy of initial
      watchful waiting. Trial registration Dutch Trial Register NTR968: ISRCTN03720485.

PMID- 21896613
TI  - RNA tertiary structure prediction with ModeRNA.
AB  - Noncoding RNAs perform important roles in the cell. As their function is tightly
      connected with structure, and as experimental methods are time-consuming and
      expensive, the field of RNA structure prediction is developing rapidly. Here, we
      present a detailed study on using the ModeRNA software. The tool uses the
      comparative modeling approach and can be applied when a structural template is
      available and an alignment of reasonable quality can be performed. We guide the
      reader through the entire process of modeling Escherichia coli tRNA(Thr) in a
      conformation corresponding to the complex with an aminoacyl-tRNA synthetase
      (aaRS). We describe the choice of a template structure, preparation of input
      files, and explore three possible modeling strategies. In the end, we evaluate
      the resulting models using six alternative benchmarks. The ModeRNA software can
      be freely downloaded from http://iimcb.genesilico.pl/moderna/ under the
      conditions of the General Public License. It runs under LINUX, Windows and Mac
      OS. It is also available as a server at
      http://iimcb.genesilico.pl/modernaserver/. The models and the script to reproduce
      the study from this article are available at
      http://www.genesilico.pl/moderna/examples/.

PMID- 21896614
TI  - A rare case of chondrocalcinosis in the left sterno-clavicular joint.

PMID- 21896615
TI  - Psychotropic drugs and accidents in Scania, Sweden.
AB  - BACKGROUND: Injuries are second to cardiovascular diseases, the main cause of
      hospital care in Sweden. The aim of the present study was to investigate the
      associations between medication with psychotropic drugs and injuries from two
      types of accidents, i.e. falling accidents and transportation accidents,
      respectively, in the whole population aged>=18 years in the county of Scania,
      Sweden. METHODS: Injuries from falling accidents and transportation accidents
      during 2007 were identified from the Region Healthcare database. Exposure to
      psychotropic medication expressed as defined daily doses (DDDs) during the 18
      months before baseline, i.e. 1 January 2007, was identified from the Swedish
      Medication Register. The results were stratified by sex and three age groups,
      i.e. 18-34 years, 35-64 years and >=65. The logistic regression models were
      adjusted for marital status, country of origin, income, previous disease and
      previous accidents. RESULTS: Using psychotropic drugs was associated with
      increased odds for a falling accident in all age groups, however, with a dose
      response relationship only among the elderly. Furthermore, using psychotropic
      drugs was associated with increased odds of transportation accidents in the ages
      18-34 years and 35-64 years, respectively, but with a weaker association among
      the elderly. A similar pattern of association was seen for specific groups of
      psychotropic drugs: opioids, anti-depressants and
      anxiolytics/hypnotics/sedatives. CONCLUSIONS: In this total population-based
      study, there were nearly consistent associations between use of psychotropic
      drugs and injuries from falling accidents and transportation accidents, even
      after adjustment for previous accidents, previous disease and socio-demographic
      variables.

PMID- 21896616
TI  - European mental health policy should target everybody.

PMID- 21896617
TI  - La enhances IRES-mediated translation of laminin B1 during malignant epithelial
      to mesenchymal transition.
AB  - The majority of transcripts that harbor an internal ribosome entry site (IRES)
      are involved in cancer development via corresponding proteins. A crucial event in
      tumor progression referred to as epithelial to mesenchymal transition (EMT)
      allows carcinoma cells to acquire invasive properties. The translational
      activation of the extracellular matrix component laminin B1 (LamB1) during EMT
      has been recently reported suggesting an IRES-mediated mechanism. In this study,
      the IRES activity of LamB1 was determined by independent bicistronic reporter
      assays. Strong evidences exclude an impact of cryptic promoter or splice sites on
      IRES-driven translation of LamB1. Furthermore, no other LamB1 mRNA species
      arising from alternative transcription start sites or polyadenylation signals
      were detected that account for its translational control. Mapping of the LamB1 5'
      untranslated region (UTR) revealed the minimal LamB1 IRES motif between -293 and 
      1 upstream of the start codon. Notably, RNA affinity purification showed that the
      La protein interacts with the LamB1 IRES. This interaction and its regulation
      during EMT were confirmed by ribonucleoprotein immunoprecipitation. In addition,
      La was able to positively modulate LamB1 IRES translation. In summary, these data
      indicate that the LamB1 IRES is activated by binding to La which leads to
      translational upregulation during hepatocellular EMT.

PMID- 21896618
TI  - How environmental solution conditions determine the compaction velocity of single
      DNA molecules.
AB  - Understanding the mechanisms of DNA compaction is becoming increasingly important
      for gene therapy and nanotechnology DNA applications. The kinetics of the
      compaction velocity of single DNA molecules was studied using two non-protein
      condensation systems, poly(ethylene glycol) (PEG) with Mg(2+) for the polymer
      salt-induced condensation system and spermine for the polyamine condensation
      system. The compaction velocities of single tandem lambda-DNA molecules were
      measured at various PEG and spermine concentrations by video fluorescent
      microscopy. Single DNA molecules were observed using a molecular stretching
      technique in the microfluidic flow. The results show that the compaction velocity
      of a single DNA molecule was proportional to the PEG or spermine concentration to
      the power of a half. Theoretical considerations indicate that the compaction
      velocity is related to differences in the free energy of a single DNA molecule
      between the random coil and compacted states. In the compaction kinetics with
      PEG, acceleration of the compaction velocity occurred above the overlap
      concentration while considerable deceleration occurred during the coexistence
      state of the random coil and the compacted conformation. This study demonstrates
      the control factors of DNA compaction kinetics and contributes toward the
      understanding of the compaction mechanisms of non-protein DNA interactions as
      well as DNA-protein interactions in vivo.

PMID- 21896619
TI  - Grapefruit juice and licorice increase cortisol availability in patients with
      Addison's disease.
AB  - OBJECTIVE: Failure to mirror the diurnal cortisol profile could contribute to the
      impaired subjective health status in Addison's disease (AD). Some patients report
      benefit from the use of various nutritional compounds. The objective of this
      study was to investigate the impact of licorice and grapefruit juice (GFJ) on the
      absorption and metabolism of cortisone acetate (CA). DESIGN: Patients (n=17) with
      AD on stable CA replacement therapy were recruited from the outpatient clinic at
      Haukeland University Hospital, Norway. They were assessed on their ordinary CA
      medication and following two 3-day periods of co-administration of licorice or
      GFJ. METHODS: Time series of glucocorticoids (GCs) in serum and saliva were
      obtained, and GCs in 24 h urine samples were determined. The main outcome measure
      was the area under the curve (AUC) for serum cortisol in the first 2.6 h after
      orally administered CA. RESULTS: Compared with the ordinary treatment, the median
      AUC for serum cortisol increased with licorice (53 783 vs 50 882, P<0.05) and GFJ
      (60 661 vs 50 882, P<0.05). Median cortisol levels in serum were also elevated
      2.6 h after tablet ingestion (licorice 223 vs 186 nmol/l, P<0.05; GFJ 337 vs 186
      nmol/l, P<0.01). Licorice increased the median urinary cortisol/cortisone ratio
      (0.43 vs 0.21, P<0.00001), whereas GFJ increased the (allo
      tetrahydrocortisol+tetrahydrocortisol)/tetrahydrocortisone ratio (0.55 vs 0.43,
      P<0.05). CONCLUSION: Licorice and in particular GFJ increased cortisol available
      to tissues in the hours following oral CA administration. Both patients and
      physicians should be aware of these interactions.

PMID- 21896621
TI  - A child with a deletion in the monocarboxylate transporter 8 gene: 7-year follow
      up and effects of thyroid hormone treatment.
AB  - OBJECTIVE: The monocarboxylate transporter 8 (MCT8; SLC16A2) has a pivotal role
      in neuronal triiodothyronine (T(3)) uptake. Mutations of this transporter
      determine a distinct X-linked psychomotor retardation syndrome (Allan-Herndon
      Dudley syndrome (AHDS)) that is attributed to disturbed thyroid hormone levels,
      especially elevated T(3) levels. We describe the genetic analysis of the MCT8
      gene in a patient suspected for AHDS and the clinical and endocrine effects of L
      thyroxine (LT(4)) or liothyronine (LT(3)) treatment intending to overcome the
      T(3) uptake resistance through alternative transporters. METHODS: The six exons
      of the MCT8 gene were amplified individually by PCR. As multiple exons were
      missing, the length of the X-chromosomal deletion was determined by a dense SNP
      array, followed by PCR-based fine mapping to define the exact borders of the
      deleted segment. The clinical and endocrine data of the patient during 6.5 years
      of LT(4) treatment and two periods (3 months each) of low- and high-dose LT(3)
      were evaluated. RESULTS: A partial deletion of the MCT8 gene (comprising five of
      six exons) was detected, confirming the suspected AHDS. MCT8 dysfunction was
      associated with partial resistance to T(3) at the hypothalamus and pituitary
      level, with normal responsiveness at the peripheral organs (liver and
      cardiovascular system). Thyroid hormone administration had no beneficial effect
      on the neurological status of the patient. CONCLUSION: We identified a 70 kb
      deletion encompassing exons 2-6 of the MCT8 gene in our AHDS patient. Both LT(4)
      and LT(3) administration had no therapeutic effect. Alternatively, treatment of
      AHDS patients with thyroid hormone analogs should be considered.

PMID- 21896620
TI  - The genetics of phaeochromocytoma: using clinical features to guide genetic
      testing.
AB  - Phaeochromocytoma is a rare, usually benign, tumour predominantly managed by
      endocrinologists. Over the last decade, major advances have been made in
      understanding the molecular genetic basis of adrenal and extra-adrenal
      phaeochromocytoma (also referred to as adrenal phaeochromocytoma (aPCA) and extra
      adrenal functional paraganglioma (eFPGL)). In contrast to the previously held
      belief that only 10% of cases had a genetic component, currently about one-third
      of all aPCA/eFPGL cases are thought to be attributable to germline mutations in
      at least nine genes (NF1, RET, SDHA, SDHB, SDHC, SDHD, TMEM127, MAX and VHL).
      Recognition of inherited cases of aPCA/eFPGL is critical for optimal patient
      management. Thus, the identification of a germline mutation can predict risks of
      malignancy, recurrent disease, associated non-chromaffin tumours and risks to
      other family members. Mutation carriers should be offered specific surveillance
      programmes (according to the relevant gene). In this review, we will describe the
      genetics of aPCA/eFPGL and strategies for genetic testing.

PMID- 21896622
TI  - Impact of clinical, hormonal, radiological, and immunohistochemical studies on
      the diagnosis of postmenopausal hyperandrogenism.
AB  - OBJECTIVE: Evaluation of postmenopausal women with suspicion of androgen
      secreting tumor. DESIGN AND PATIENTS: We retrospectively studied 22
      postmenopausal women referred to our center for suspicion of androgen-secreting
      tumor. All patients had clinical, biological, and morphological evaluation. In
      absence of adrenal tumors, ovarian surgery was most often proposed and
      immunohistochemistry (IHC) studies were performed. RESULTS: Ovarian tumors were
      detected by ultrasound and/or magnetic resonance imaging in eight patients. Two
      adrenal androgen-secreting tumors were diagnosed by an adrenal computed
      tomography (CT) scan. The clinical presentation of the women with or without
      tumors was similar. Nevertheless, women with tumor exhibited significantly higher
      testosterone levels and lower basal FSH and LH levels than the other women (2.6+/
      2.7 vs 0.9+/-0.9 ng/ml, P<0.05; 26.5+/-22.9 vs 66.5+/-26.0 IU/l, P<0.01; and
      12.0+/-8.6 vs 24.1+/-8.9 IU/l, P<0.05 respectively). Based on a likelihood ratio
      test, patients with a tumor had 8.4 and 10.8 times higher risk of having a
      testosterone level >=1.4 ng/ml or an FSH level <=35 IU/l. Finally, IHC analysis
      with an anti-P450c17alpha antibody allowed the identification of an elevated
      number of ovarian androgen-producing cells in five patients in whom no tumor was
      found. CONCLUSIONS: Androgen-secreting tumors are clinically difficult to
      discriminate from other causes of postmenopausal hyperandrogenism. Testosterone
      and FSH were the two discriminative markers in a multivariate analysis. Ovarian
      and adrenal tumors were detected by imaging studies. However, ovarian non-tumoral
      causes of hyperandrogenism may be difficult to detect with conventional
      histology.

PMID- 21896623
TI  - The GINA Asthma Challenge: reducing asthma hospitalisations.

PMID- 21896624
TI  - Multi-Link Vision stent vs. first-generation drug-eluting stents: systematic
      review and meta-analysis.
AB  - BACKGROUND: Since its introduction, the cobalt chromium alloy MULTI-LINK VISION
      stent (MLV) has been extensively investigated thus leading to the largest amount
      of data so far available for a bare metal stent. Aim and METHODS: Systematic
      review and meta-analysis (according to Cochrane collaboration guidelines) aiming
      at summarizing the real world safety and efficacy of MLV stent. Endpoints of
      interest were: major adverse events [(MAE) combination of overall death and non
      fatal myocardial infarction, MI], and target vessel revascularization (TVR). Rate
      of stent thrombosis was also assessed. RESULTS: Eleven studies finally retrieved
      totalling 5539 patients [7 study registries, 4243 patients and 4 randomized
      controlled trials (RCTs) comparing MLV vs. first generation of drug-eluting stent
      (DES) (paclitaxel or sirolimus eluting), (RCTs) 1296 patients]. Across study
      registries, at a mean follow-up of 11.1 months, MLV was associated with a 5.3%
      risk of MAE, 3% of death, 2.3% of MI and a 9% of TVR. Risk of ST was 0.5%.
      Compared to first generation of DES in RCTs, at a mean follow-up of 10.5 months,
      MLV achieved similar results in terms of MAE, death and MI. On the other hand,
      MLV was associated with a double risk of TVR [OR 2.01 (1.34-3.01), P < 0.001,
      number needed to treat 18 (13-40)]. Overall, in stent late loss with MLV was 0.81
      mm (+/-0.51), while the in segment late loss was 0.61 mm (+/-0.5). Risk of stent
      thrombosis was equivalent. Of note, performance of MLV in terms of safety,
      efficacy and risk of repeat revascularization was quite consistent across all the
      published studies, despite inherent differences in study design, clinical
      setting, complexity of the lesions and ethnicity. CONCLUSION: Compared to first
      generation DES, MLV showed substantial equivalence with respect to hard clinical
      endpoints. Data are consistent in study registries and RCTs meaning that the
      overall performance of MLV is quite predictable and reproducible into the wide
      spectrum of clinical settings.

PMID- 21896625
TI  - Leaving the lab: career development for developmental biologists.

PMID- 21896626
TI  - Modeling new conceptual interpretations of development.
AB  - In April 2011, researchers from diverse background met at the Gulbenkian
      Institute (Oeiras, Portugal) to discuss the emerging input of biophysics into the
      field of developmental biology. The scope of the workshop was to bring together
      scientists working in different model systems and to discuss some of the most
      recent advances towards understanding how physical forces affect embryonic
      development. Discussions and talks highlighted two main trends: that many aspects
      of embryogenesis can be accurately quantified and translated into a limited
      number of physical forces and biochemical parameters; and that simulations and
      modeling provide new conceptual interpretations of classical developmental
      questions.

PMID- 21896627
TI  - The control of developmental phase transitions in plants.
AB  - Plant development progresses through distinct phases: vegetative growth, followed
      by a reproductive phase and eventually seed set and senescence. The transitions
      between these phases are controlled by distinct genetic circuits that integrate
      endogenous and environmental cues. In recent years, however, it has become
      evident that the genetic networks that underlie these phase transitions share
      some common factors. Here, we review recent advances in the field of plant phase
      transitions, highlighting the role of two microRNAs - miR156 and miR172 - and
      their respective targets during these transitions. In addition, we discuss the
      evolutionary conservation of the functions of these miRNAs in regulating the
      control of plant developmental phase transitions.

PMID- 21896628
TI  - Secreted frizzled-related proteins are required for Wnt/beta-catenin signalling
      activation in the vertebrate optic cup.
AB  - Secreted frizzled-related proteins (Sfrps) are considered Wnt signalling
      antagonists but recent studies have shown that specific family members enhance
      Wnt diffusion and thus positively modulate Wnt signalling. Whether this is a
      general and physiological property of all Sfrps remains unexplored. It is equally
      unclear whether disruption of Sfrp expression interferes with developmental
      events mediated by Wnt signalling activation. Here, we have addressed these
      questions by investigating the functional consequences of Sfrp disruption in the
      canonical Wnt signalling-dependent specification of the mouse optic cup
      periphery. We show that compound genetic inactivation of Sfrp1 and Sfrp2 prevents
      Wnt/beta-catenin signalling activation in this structure, which fails to be
      specified and acquires neural retina characteristics. Consistent with a positive
      role of Sfrps in signalling activation, Wnt spreading is impaired in the retina
      of Sfrp1(-/-);Sfrp2(-/-) mice. Conversely, forced expression of Sfrp1 in the wing
      imaginal disc of Drosophila, the only species in which the endogenous Wnt
      distribution can be detected, flattens the Wg gradient, suppresses the expression
      of high-Wg target genes but expands those typically activated by low Wg
      concentrations. Collectively, these data demonstrate that, in vivo, the levels of
      Wnt signalling activation strongly depend on the tissue distribution of Sfrps,
      which should be viewed as multifunctional regulators of Wnt signalling.

PMID- 21896629
TI  - Transmembrane protein 2 (Tmem2) is required to regionally restrict
      atrioventricular canal boundary and endocardial cushion development.
AB  - The atrioventricular canal (AVC) physically separates the atrial and ventricular
      chambers of the heart and plays a crucial role in the development of the valves
      and septa. Defects in AVC development result in aberrant heart morphogenesis and
      are a significant cause of congenital heart malformations. We have used a forward
      genetic screen in zebrafish to identify novel regulators of cardiac
      morphogenesis. We isolated a mutant, named wickham (wkm), that was
      indistinguishable from siblings at the linear heart tube stage but exhibited a
      specific loss of cardiac looping at later developmental stages. Positional
      cloning revealed that the wkm locus encodes transmembrane protein 2 (Tmem2), a
      single-pass transmembrane protein of previously unknown function. Expression
      analysis demonstrated myocardial and endocardial expression of tmem2 in zebrafish
      and conserved expression in the endocardium of mouse embryos. Detailed phenotypic
      analysis of the wkm mutant identified an expansion of expression of known
      myocardial and endocardial AVC markers, including bmp4 and has2. By contrast, a
      reduction in the expression of spp1, a marker of the maturing valvular primordia,
      was observed, suggesting that an expansion of immature AVC is detrimental to
      later valve maturation. Finally, we show that immature AVC expansion in wkm
      mutants is rescued by depleting Bmp4, indicating that Tmem2 restricts bmp4
      expression to delimit the AVC primordium during cardiac development.

PMID- 21896630
TI  - The novel transmembrane protein Tmem2 is essential for coordination of myocardial
      and endocardial morphogenesis.
AB  - Coordination between adjacent tissues plays a crucial role during the
      morphogenesis of developing organs. In the embryonic heart, two tissues - the
      myocardium and the endocardium - are closely juxtaposed throughout their
      development. Myocardial and endocardial cells originate in neighboring regions of
      the lateral mesoderm, migrate medially in a synchronized fashion, collaborate to
      create concentric layers of the heart tube, and communicate during formation of
      the atrioventricular canal. Here, we identify a novel transmembrane protein,
      Tmem2, that has important functions during both myocardial and endocardial
      morphogenesis. We find that the zebrafish mutation frozen ventricle (frv) causes
      ectopic atrioventricular canal characteristics in the ventricular myocardium and
      endocardium, indicating a role of frv in the regional restriction of
      atrioventricular canal differentiation. Furthermore, in maternal-zygotic frv
      mutants, both myocardial and endocardial cells fail to move to the midline
      normally, indicating that frv facilitates cardiac fusion. Positional cloning
      reveals that the frv locus encodes Tmem2, a predicted type II single-pass
      transmembrane protein. Homologs of Tmem2 are present in all examined vertebrate
      genomes, but nothing is known about its molecular or cellular function in any
      context. By employing transgenes to drive tissue-specific expression of tmem2, we
      find that Tmem2 can function in the endocardium to repress atrioventricular
      differentiation within the ventricle. Additionally, Tmem2 can function in the
      myocardium to promote the medial movement of both myocardial and endocardial
      cells. Together, our data reveal that Tmem2 is an essential mediator of
      myocardium-endocardium coordination during cardiac morphogenesis.

PMID- 21896631
TI  - HP1gamma links histone methylation marks to meiotic synapsis in mice.
AB  - During meiosis, specific histone modifications at pericentric heterochromatin
      (PCH), especially histone H3 tri- and dimethylation at lysine 9 (H3K9me3 and
      H3K9me2, respectively), are required for proper chromosome interactions. However,
      the molecular mechanism by which H3K9 methylation mediates the synapsis is not
      yet understood. We have generated a Cbx3-deficient mouse line and performed
      comparative analysis on Suv39h1/h2-, G9a- and Cbx3-deficient spermatocytes. This
      study revealed that H3K9me2 at PCH depended on Suv39h1/h2-mediated H3K9me3 and
      its recognition by the Cbx3 gene product HP1gamma. We further found that
      centromere clustering and synapsis were commonly affected in G9a- and Cbx3
      deficient spermatocytes. These genetic observations suggest that HP1gamma/G9a
      dependent PCH-mediated centromere clustering is an axis for proper chromosome
      interactions during meiotic prophase. We propose that the role of the
      HP1gamma/G9a axis is to retain centromeric regions of unpaired homologous
      chromosomes in close alignment and facilitate progression of their pairing in
      early meiotic prophase. This study also reveals considerable plasticity in the
      interplay between different histone modifications and suggests that such stepwise
      and dynamic epigenetic modifications may play a pivotal role in meiosis.

PMID- 21896632
TI  - Specific expression of a TRIM-containing factor in ectoderm cells affects the
      skeletal morphogenetic program of the sea urchin embryo.
AB  - In the indirect developing sea urchin embryo, the primary mesenchyme cells (PMCs)
      acquire most of the positional and temporal information from the overlying
      ectoderm for skeletal initiation and growth. In this study, we characterize the
      function of the novel gene strim1, which encodes a tripartite motif-containing
      (TRIM) protein, that adds to the list of genes constituting the epithelial
      mesenchymal signaling network. We report that strim1 is expressed in ectoderm
      regions adjacent to the bilateral clusters of PMCs and that its misexpression
      leads to severe skeletal abnormalities. Reciprocally, knock down of strim1
      function abrogates PMC positioning and blocks skeletogenesis. Blastomere
      transplantation experiments establish that the defects in PMC patterning, number
      and skeletal growth depend upon strim1 misexpression in ectoderm cells.
      Furthermore, clonal expression of strim1 into knocked down embryos locally
      restores skeletogenesis. We also provide evidence that the Otp and Pax2/5/8
      regulators, as well as FGFA, but not VEGF, ligand act downstream to strim1 in
      ectoderm cells, and that strim1 triggers the expression of the PMC marker sm30,
      an ectoderm-signaling dependent gene. We conclude that the strim1 function
      elicits specific gene expression both in ectoderm cells and PMCs to guide the
      skeletal biomineralization during morphogenesis.

PMID- 21896633
TI  - Multisite haplotype on cattle chromosome 3 is associated with quantitative trait
      locus effects on lactation traits.
AB  - The goal of this study was to identify candidate genes and DNA polymorphisms for
      quantitative trait loci (QTL) affecting milk yield (MY), fat yield (FY), and
      protein yield (PY) previously mapped to bovine chromosome 3 (BTA3). To accomplish
      this, 373 half-siblings sired by three bulls previously shown to be segregating
      for lactation trait QTL, and 263 additional sires in the U.S. Dairy Bull DNA
      Repository (DBDR) were genotyped for 2,500 SNPs within a 16.3 Mbp QTL critical
      region on BTA3. Targeted resequencing of ~1.8 Mbp within the QTL critical region
      of one of the QTL heterozygous sires identified additional polymorphisms useful
      for association studies. Twenty-three single nucleotide polymorphisms (SNPs)
      within a fine-mapped region were associated with effects on breeding values for
      MY, FY, or PY in DBDR sires, of which five SNPs were in strong linkage
      disequilibrium in the population. This multisite haplotype included SNPs located
      within exons or promoters of four tightly linked genes: RAP1A, ADORA3, OVGP1, and
      C3H1orf88. An SNP within RAP1A showed strong evidence of a recent selective sweep
      based on integrated haplotype score and was also associated with breeding value
      for PY. Because of its known function in alveolar lumen formation in the mammary
      gland, RAP1A is thus a strong candidate gene for QTL effects on lactation traits.
      Our results provide a detailed assessment of a QTL region that will be a useful
      guide for complex traits analysis in humans and other noninbred species.

PMID- 21896635
TI  - Differences in the participation of TGFB superfamily signalling pathways
      mediating porcine and murine cumulus cell expansion.
AB  - It is widely held that mammalian cumulus cell (CC) expansion requires oocyte
      paracrine signalling, however in three of the four species studied to date, CC
      expansion occurs in the absence of the oocyte. This study was conducted to
      examine the paracrine and SMAD/MAPK intracellular signalling mechanism mediating
      porcine CC expansion, and to compare these to the mouse. Cumulus-oocyte complexes
      (COCs) and oocyte-free complexes (OOXs) from pigs and eCG-primed mice were
      treated in vitro with FSH and a broad range of TGFB superfamily antagonists.
      Expansion of porcine COCs and OOXs was unaffected by neutralisation of growth
      differentiation factor 9, TGFB, activin A, activin B and a broad spectrum bone
      morphogenetic protein antagonist. A SMAD-responsive luciferase reporter assay
      confirmed that porcine oocytes secreted factors that activate SMAD3 and SMAD1/5/8
      in granulosa cells, but murine oocytes activated SMAD3 only. Treatment of COCs
      with a SMAD2/3 phosphorylation inhibitor (SB431542) partially inhibited porcine
      CC expansion and expression of TNFAIP6, but ablated murine CC expansion. SB431542
      was equally effective at attenuating porcine CC expansion in the presence or
      absence of the oocyte. By contrast, a SMAD1/5/8 phosphorylation inhibitor
      (dorsomorphin) had no effect on porcine or murine CC function. Inhibition of
      ERK1/2 and p38 MAPK signalling pathways prevented porcine COC expansion and
      expression of most matrix genes examined. The activation of CC SMAD signalling by
      oocytes, and the requirement of SMAD2/3 signalling for expansion, is notably
      contrasted in pigs and mice. Nonetheless, porcine CC SMAD2/3 signalling is likely
      to be needed for optimal matrix formation, possibly by facilitating essential
      MAPK signals.

PMID- 21896636
TI  - The Sda/GM2-glycan is a carbohydrate marker of porcine primordial germ cells and
      of a subpopulation of spermatogonia in cattle, pigs, horses and llama.
AB  - Spermatogonia are a potential source of adult pluripotent stem cells and can be
      used for testis germ cell transplantation. Markers for the isolation of these
      cells are of great importance for biomedical applications. Primordial germ cells
      and prepubertal spermatogonia in many species can be identified by their binding
      of Dolichos biflorus agglutinin (DBA). This lectin binds to two different types
      of glycans, which are alpha-linked N-acetylgalactosamine (GalNac) and beta-linked
      GalNac, if this is part of the Sda or GM2 glycotopes. We used the MAB CT1, which
      is specific for the trisaccharides motif NeuAcalpha2-3(GalNAcbeta1-4)Galbeta1-,
      which is common to both Sda and GM2 glycotopes, to further define the
      glycosylation of DBA binding germ cells. In porcine embryos, CT1 bound to
      migratory germ cells and gonocytes. CT1/DBA double staining showed that the
      mesonephros was CT1 negative but contained DBA-positive cells. Gonocytes in the
      female gonad became CT1 negative, while male gonocytes remained CT1 positive. In
      immunohistological double staining of cattle, pig, horse and llama testis, DBA
      and CT1 staining was generally colocalised in a subpopulation of spermatogonia.
      These spermatogonia were mainly single, sometimes paired or formed chains of up
      to four cells. Our data show that the Sda/GM2 glycotope is present in developing
      germ cells and spermatogonia in several species. Owing to the narrower
      specificity of the CT1 antibody, compared with DBA, the former is likely to be a
      useful tool for labelling and isolation of these cells.

PMID- 21896634
TI  - What makes hospitalized patients more vulnerable and increases their risk of
      experiencing an adverse event?
AB  - OBJECTIVE: To analyze the relationship between the appearance of adverse events
      (AEs) and both patient comorbidities and the use of medical devices. DESIGN:
      Retrospective medical records review study. SETTING: Twenty-four Spanish public
      hospitals. PARTICIPANTS: Clinical records of 5624 discharged patients. MAIN
      OUTCOME MEASURE: Incidence of AEs. RESULTS: Patients aged >65 have 2.4 times the
      risk of experiencing an AE compared with those aged <65. The presence of certain
      comorbidities and devices (neoplasia, chronic hepatic alteration, cardiac
      insufficiency, coronary disease, high blood pressure, urethral catheterization,
      catheterization of a vessel, tracheostomy or stay of >7 days) were associated
      with developing an AE during hospitalization. There is a trend effect if we
      consider the number of comorbidities and the number of devices used. Thus, the
      risk of an AE in subjects who present no comorbidities was 3.2%, which rose to
      9.9% in those with one intrinsic risk factor, 16.7% in those with two and 29.3%
      in those with three or more. Similarly, subjects without extrinsic risk factor
      experienced an AE in 4.4% of cases, which rose to 9.6% when there was one risk
      factor, to 13.4% when there were two and to 33.0% when there were three or more
      risk factors. The effect of some of these pathologies and that associated with
      age disappeared on adjusting in line with other variables. CONCLUSIONS: The true
      risk resides in the number of exposures to potentially iatrogenic actions, rather
      than being intrinsic to age or the presence of certain comorbidities.

PMID- 21896637
TI  - Exploring the hidden heritability of inflammatory bowel disease.

PMID- 21896638
TI  - Ablation of sphingosine kinase-2 inhibits tumor cell proliferation and migration.
AB  - Sphingosine kinases (SK) regulate the balance between proapoptotic ceramides and
      mitogenic sphingosine-1-phosphate (S1P); however, the functions of the two
      isoenzymes (SK1 and SK2) in tumor cells are not well defined. Therefore, RNA
      interference was used to assess the individual roles of SK1 and SK2 in tumor cell
      sphingolipid metabolism, proliferation, and migration/invasion. Treatment of
      A498, Caki-1, or MDA-MB-231 cells with siRNAs specific for SK1 or SK2 effectively
      suppressed the expression of the target mRNA and protein. Ablation of SK1 did not
      affect mRNA or protein levels of SK2 and reduced intracellular levels of S1P
      while elevating ceramide levels. In contrast, ablation of SK2 elevated mRNA,
      protein, and activity levels of SK1 and increased cellular S1P levels.
      Interestingly, cell proliferation and migration/invasion were suppressed more by
      SK2-selective ablation than by SK1-selective ablation, showing that the increased
      S1P does not rescue these phenotypes. Similarly, exogenous S1P did not rescue the
      cells from the antiproliferative or antimigratory effects of the siRNAs.
      Consistent with these results, differential effects of SK1- and SK2-selective
      siRNAs on signaling proteins, including p53, p21, ERK1, ERK2, FAK, and VCAM1,
      indicate that SK1 and SK2 have only partially overlapping functions in tumor
      cells. Overall, these data indicate that loss of SK2 has stronger anticancer
      effects than does suppression of SK1. Consequently, selective inhibitors of SK2
      may provide optimal targeting of this pathway in cancer chemotherapy.

PMID- 21896640
TI  - Circulating tumor cell isolation and diagnostics: toward routine clinical use.
AB  - From February 7-11, 2011, the multidisciplinary Lorentz Workshop Circulating
      Tumor Cell (CTC) Isolation and Diagnostics: Toward Routine Clinical Use was held
      in Leiden (The Netherlands) to discuss progress and define challenges and
      potential solutions for development of clinically useful circulating tumor cell
      (CTC) diagnostics. CTCs, captured as "liquid biopsy" from blood, for counting and
      characterization using pathology and molecular assays, are expected to replace
      metastatic tissue biopsies to be used to predict drug response and resistance and
      to monitor therapy response and cancer recurrence. CTCs are highly heterogeneous;
      therefore, cancer type-specific isolation technologies, as well as complex
      clinical interpretation software, are required.

PMID- 21896639
TI  - Itraconazole inhibits angiogenesis and tumor growth in non-small cell lung
      cancer.
AB  - The antiangiogenic agent bevacizumab has been approved for the treatment of non
      small cell lung cancer (NSCLC), although the survival benefit associated with
      this agent is marginal, and toxicities and cost are substantial. A recent screen
      for selective inhibitors of endothelial cell proliferation identified the oral
      antifungal drug itraconazole as a novel agent with potential antiangiogenic
      activity. In this article, we define and characterize the antiangiogenic and
      anticancer activities of itraconazole in relevant preclinical models of
      angiogenesis and lung cancer. Itraconazole consistently showed potent, specific,
      and dose-dependent inhibition of endothelial cell proliferation, migration, and
      tube formation in response to both VEGF- and basic fibroblast growth factor
      mediated angiogenic stimulation. In vivo, using primary xenograft models of human
      NSCLC, oral itraconazole showed single-agent growth-inhibitory activity
      associated with induction of tumor hypoxia-inducible factor 1 alpha expression
      and marked inhibition of tumor vascularity. Itraconazole significantly enhanced
      the antitumor efficacy of the chemotherapeutic agent cisplatin in the same model
      systems. Taken together, these data suggest that itraconazole has potent and
      selective inhibitory activity against multiple key aspects of tumor-associated
      angiogenesis in vitro and in vivo, and strongly support clinical translation of
      its use. Based on these observations, we have initiated a randomized phase II
      study comparing the efficacy of standard cytotoxic therapy with or without daily
      oral itraconazole in patients with recurrent metastatic NSCLC.

PMID- 21896641
TI  - Mast cell targeting hampers prostate adenocarcinoma development but promotes the
      occurrence of highly malignant neuroendocrine cancers.
AB  - Mast cells (MC) are c-Kit-expressing cells, best known for their primary
      involvement in allergic reactions, but recently reappraised as important players
      in either cancer promotion or inhibition. Here, we assessed the role of MCs in
      prostate tumor development. In prostate tumors from both tumor-prone transgenic
      adenocarcinoma of the mouse prostate (TRAMP) mice and human patients, MCs are
      specifically enriched and degranulated in areas of well-differentiated (WD)
      adenocarcinoma but not around poorly differentiated (PD) foci that coexist in the
      same tumors. We derived novel TRAMP tumor cell lines, representative of WD and PD
      variants, and through pharmacologic stabilization or genetic ablation of MCs in
      recipients mice, we showed that MCs promote WD adenocarcinoma growth but are
      dispensable for PD tumors. WD tumors rely on MCs for matrix metalloprotease 9
      (MMP-9) provision, as reconstitution of MC-deficient mice with wild-type but not
      MMP-9(-/-) MCs was sufficient to promote their growth. In contrast, PD tumors are
      MMP-9 self-competent, consistently with epithelial-to-mesenchymal transition.
      Such a dual source of MMP-9 was confirmed in human tumors, suggesting that MCs
      could be a good target for early-stage prostate cancer. Interestingly, in testing
      whether MC targeting could block or delay tumorigenesis in tumor-prone TRAMP
      mice, we observed a high incidence of early and aggressive tumors, characterized
      by a neuroendocrine (NE) signature and c-Kit expression. Taken together, these
      data underscore the contribution of MCs in tumor progression and uncover a new,
      opposite role of MCs in protecting against the occurrence of aggressive NE
      variants in prostate cancer.

PMID- 21896642
TI  - Systems biology: confronting the complexity of cancer.
AB  - The AACR-NCI Conference "Systems Biology: Confronting the Complexity of Cancer"
      took place from February 27 to March 2, 2011, in San Diego, CA. Several themes
      resonated during the meeting, notably (i) the need for better methods to distill
      insights from large-scale networks, (ii) the importance of integrating multiple
      data types in constructing more realistic models, (iii) challenges in translating
      insights about tumorigenic mechanisms into therapeutic interventions, and (iv)
      the role of the tumor microenvironment, at the physical, cellular, and molecular
      levels. The meeting highlighted concrete applications of systems biology to
      cancer, and the value of collaboration between interdisciplinary researchers in
      attacking formidable problems.

PMID- 21896643
TI  - Very-long-chain fatty acids are required for cell plate formation during
      cytokinesis in Arabidopsis thaliana.
AB  - Acyl chain length is thought to be crucial for biophysical properties of the
      membrane, in particular during cell division, when active vesicular fusion is
      necessary. In higher plants, the process of cytokinesis is unique, because the
      separation of the two daughter cells is carried out by de novo vesicular fusion
      to generate a laterally expanding cell plate. In Arabidopsis thaliana, very-long
      chain fatty acid (VLCFA) depletion caused by a mutation in the microsomal
      elongase gene PASTICCINO2 (PAS2) or by application of the selective elongase
      inhibitor flufenacet altered cytokinesis. Cell plate expansion was delayed and
      the formation of the endomembrane tubular network altered. These defects were
      associated with specific aggregation of the cell plate markers YFP-Rab-A2a and
      KNOLLE during cytokinesis. Changes in levels of VLCFA also resulted in
      modification of endocytosis and sensitivity to brefeldin A. Finally, the
      cytokinesis impairment in pas2 cells was associated with reduced levels of very
      long fatty acyl chains in phospholipids. Together, our findings demonstrate that
      VLCFA-containing lipids are essential for endomembrane dynamics during
      cytokinesis.

PMID- 21896644
TI  - TRB3 interacts with SMAD3 promoting tumor cell migration and invasion.
AB  - Tribbles homolog 3 (TRB3, also known as TRIB3, NIPK and SKIP3), a human homolog
      of Drosophila Tribbles, has been found to interact with a variety of signaling
      molecules to regulate diverse cellular functions. Here, we report that TRB3 is a
      novel SMAD3-interacting protein. Expression of exogenous TRB3 enhanced the
      transcriptional activity of SMAD3, whereas knocking down endogenous TRB3 reduced
      the transcriptional activity of SMAD3. The kinase-like domain (KD) of TRB3 was
      responsible for the interaction with SMAD3 and the regulation of SMAD3-mediated
      transcriptional activity. In addition, TGF-beta1 stimulation or overexpression of
      SMAD3 enhanced the TRB3 promoter activity and expression, suggesting that there
      is a positive feedback loop between TRB3 and TGF-beta-SMAD3 signaling.
      Mechanistically, TRB3 was found to trigger the degradation of SMAD ubiquitin
      regulatory factor 2 (Smurf2), which resulted in a decrease in the degradation of
      SMAD2 and phosphorylated SMAD3. Moreover, TRB3-SMAD3 interaction promoted the
      nuclear localization of SMAD3 because of the interaction of TRB3 with the MH2
      domain of SMAD3. These effects of TRB3 were responsible for potentiating the
      SMAD3-mediated activity. Furthermore, knockdown of endogenous TRB3 expression
      inhibited the migration and invasion of tumor cells in vitro, which were
      associated with an increase in the expression of E-cadherin and a decrease in the
      expression of Twist-1 and Snail, two master regulators of epithelial-to
      mesenchymal transition, suggesting a crucial role for TRB3 in maintaining the
      mesenchymal status of tumor cells. These results demonstrate that TRB3 acts as a
      novel SMAD3-interacting protein to participate in the positive regulation of TGF
      beta-SMAD-mediated cellular biological functions.

PMID- 21896646
TI  - Influence of matrix metalloproteinase MMP-9 on dendritic spine morphology.
AB  - An increasing body of data has shown that matrix metalloproteinase-9 (MMP-9), an
      extracellularly acting, Zn(2+)-dependent endopeptidase, is important not only for
      pathologies of the central nervous system but also for neuronal plasticity. Here,
      we use three independent experimental models to show that enzymatic activity of
      MMP-9 causes elongation and thinning of dendritic spines in the hippocampal
      neurons. These models are: a recently developed transgenic rat overexpressing
      autoactivating MMP-9, dissociated neuronal cultures, and organotypic neuronal
      cultures treated with recombinant autoactivating MMP-9. This dendritic effect is
      mediated by integrin beta1 signalling. MMP-9 treatment also produces a change in
      the decay time of miniature synaptic currents; however, it does not change the
      abundance and localization of synaptic markers in dendritic protrusions. Our
      results, considered together with several recent studies, strongly imply that MMP
      9 is functionally involved in synaptic remodelling.

PMID- 21896645
TI  - Mutations associated with Charcot-Marie-Tooth disease cause SIMPLE protein
      mislocalization and degradation by the proteasome and aggresome-autophagy
      pathways.
AB  - Mutations in SIMPLE cause an autosomal dominant, demyelinating form of peripheral
      neuropathy termed Charcot-Marie-Tooth disease type 1C (CMT1C), but the pathogenic
      mechanisms of these mutations remain unknown. Here, we report that SIMPLE is an
      early endosomal membrane protein that is highly expressed in the peripheral
      nerves and Schwann cells. Our analysis has identified a transmembrane domain
      (TMD) embedded within the cysteine-rich (C-rich) region that anchors SIMPLE to
      the membrane, and suggests that SIMPLE is a post-translationally inserted, C-tail
      anchored membrane protein. We found that CMT1C-linked pathogenic mutations are
      clustered within or around the TMD of SIMPLE and that these mutations cause
      mislocalization of SIMPLE from the early endosome membrane to the cytosol. The
      CMT1C-associated SIMPLE mutant proteins are unstable and prone to aggregation,
      and they are selectively degraded by both the proteasome and aggresome-autophagy
      pathways. Our findings suggest that SIMPLE mutations cause CMT1C peripheral
      neuropathy by a combination of loss-of-function and toxic gain-of-function
      mechanisms, and highlight the importance of both the proteasome and autophagy
      pathways in the clearance of CMT1C-associated mutant SIMPLE proteins.

PMID- 21896647
TI  - Changes in BiP availability reveal hypersensitivity to acute endoplasmic
      reticulum stress in cells expressing mutant huntingtin.
AB  - Huntington's disease (HD) is caused by expanded glutamine repeats within the
      huntingtin (Htt) protein. Mutant Htt (mHtt) in the cytoplasm has been linked to
      induction of the luminal endoplasmic reticulum (ER) stress pathway, the unfolded
      protein response (UPR). How mHtt impacts the susceptibility of the ER lumen to
      stress remains poorly understood. To investigate molecular differences in the ER
      in cells expressing mHtt, we used live-cell imaging of a sensitive reporter of
      the misfolded secretory protein burden, GFP fused to the ER chaperone BiP (also
      known as GRP78), which decreases in mobility as it binds increasing amounts of
      misfolded proteins. Striatal neurons expressing full-length mHtt showed no
      differences in BiP-GFP mobility and no evidence of UPR activation compared with
      wild-type cells at steady state. However, mHtt-expressing cells were acutely
      sensitive to misfolded secretory proteins. Treatment with ER stressors,
      tunicamycin or DTT, rapidly decreased BiP-GFP mobility in mHtt striatal cells and
      accelerated UPR activation compared with wild-type cells. mHtt-expressing cells
      exhibited decreased misfolded protein flux as a result of ER associated
      degradation (ERAD) dysfunction. Furthermore, UPR-adapted mHtt cells succumbed to
      misfolded protein stresses that could be tolerated by adapted wild-type cells.
      Thus, mHtt expression impairs misfolded secretory protein turnover, decreases the
      ER stress threshold, and increases cell vulnerability to insults.

PMID- 21896648
TI  - Drosophila Swiprosin-1/EFHD2 accumulates at the prefusion complex stage during
      Drosophila myoblast fusion.
AB  - In the Drosophila embryo, transient cell adhesion during myoblast fusion is known
      to lead to the formation of fusion-restricted myogenic-adhesive structures
      (FuRMASs). Here, we report that within these FuRMASs, a Drosophila homologue of
      human and mouse swiprosins (EF-hand-domain-containing proteins) is expressed,
      which we named Drosophila Swiprosin-1 (Drosophila Swip-1). Drosophila Swip-1 is
      highly conserved and is closely related to the calcium-binding proteins swiprosin
      1 and swiprosin-2 that have a role in the immune system in humans and mice. Our
      study shows that Drosophila Swip-1 is also expressed in corresponding cells of
      the Drosophila immune system. During myoblast fusion, Drosophila Swip-1
      accumulates transiently in the foci of fusion-competent myoblasts (FCMs). Both
      the EF-hand and the coiled-coil domain of Drosophila Swip-1 are required to
      localise the protein to these foci. The formation of Drosophila Swip-1 foci
      requires successful cell adhesion between FCMs and founder cells (FCs) or growing
      myotubes. Moreover, Drosophila Swip-1 foci were found to increase in number in
      sing(22) mutants, which arrest myoblast fusion after prefusion complex formation.
      By contrast, Drosophila Swip-1 foci are not significantly enriched in blow(2) and
      kette(J4-48) mutants, which stop myogenesis beyond the prefusion complex stage
      but before plasma membrane merging. Therefore, we hypothesise that Drosophila
      Swip-1 participates in the breakdown of the prefusion complex during the
      progression of myoblast fusion.

PMID- 21896649
TI  - Boxing bladder cancer with COX-2-specific inhibition.
AB  - Preventing recurrence of non-muscle-invasive bladder cancer (NMIBC) is important
      for improving patient well-being and reducing the health economic burden of this
      disease. To date, no oral agent has shown sufficient benefit to be adopted in
      clinical practice, where current strategies rely on topical (intravesical)
      administration of chemotherapy and immunotherapy. In this issue of the journal
      (beginning on page 1580), Sabichi and colleagues report the first phase II
      randomized controlled trial of the COX-2 inhibitor celecoxib in bladder cancer.
      The trial set out to measure an overly ambitious effect size but nevertheless
      showed encouraging signs of celecoxib activity. It lends support to COX-2
      inhibition in NMIBC, which is being tested in several subsequent trials, and to
      the need for conclusive evidence.

PMID- 21896652
TI  - Wnt signaling meets internal dissent.
AB  - In canonical Wnt signaling, beta-catenin translocates to the cell nucleus,
      interacting with Tcf/Lef factors to activate transcription of Wnt target genes.
      In this issue of Genes & Development, Vacik and colleagues (pp. 1783-1795) report
      that a highly conserved sequence in intron 5 of Tcf7l2 conceals an internal
      promoter region that, when activated by Vax2, drives transcription of truncated
      Tcf7l2 mRNAs. The encoded Tcf7l2 protein binds to DNA, but not beta-catenin, and
      therefore acts as a dominant-negative Wnt antagonist.

PMID- 21896650
TI  - Phase III trial of selenium to prevent prostate cancer in men with high-grade
      prostatic intraepithelial neoplasia: SWOG S9917.
AB  - The threat of prostate cancer and the significant and often negative impact of
      its treatment underscore the importance of prevention. High-grade prostatic
      intraepithelial neoplasia (HGPIN) has been identified as a potential premalignant
      lesion marking an increased risk of prostate cancer and substantial evidence
      suggests that men with HGPIN are in need of prostate cancer prevention. In vitro,
      in vivo, epidemiologic, and clinical trial evidence that selenium supplementation
      protects against prostate cancer motivated the study we report here: a double
      blind, randomized, placebo-controlled trial of selenium 200 (MUg/d) as
      selenomethionine in men with HGPIN. The primary endpoint was progression of HGPIN
      to prostate cancer over a 3-year period. This National Cancer Institute
      Intergroup trial was coordinated by the Southwest Oncology Group (SWOG). Of 619
      enrolled patients, 423 randomized men with HGPIN (212 selenium and 211 placebo)
      were eligible (by central pathology review) and included in the primary analysis.
      Three-year cancer rates were 36.6% (placebo) versus 35.6% (selenium; P = 0.73,
      adjusted). The majority of patients who developed cancer on trial (70.8%,
      selenium and 75.5%, placebo) had a Gleason score of 6 or less than 6; there were
      no differences in Gleason scores between the two arms. Subset analyses included
      the finding of a nonsignificantly reduced prostate cancer risk (relative risk =
      0.82; 95% CI: 0.40-1.69) in selenium versus placebo patients in the lowest
      quartile of baseline plasma selenium level (<106 ng/mL). Overall, and in all
      other subsets defined by baseline blood selenium levels, selenium supplementation
      had no effect on prostate cancer risk. The 36% prostate cancer rate in men with
      HGPIN indicates the association of this lesion with an elevated prostate cancer
      risk. Future study in this setting should focus on selenium-deficient populations
      and selenium pharmacogenetics.

PMID- 21896651
TI  - Viruses and microRNAs: RISCy interactions with serious consequences.
AB  - Analyses of small RNA expression profiles have revealed that several DNA viruses
      including particularly, herpesviruses-express high levels of multiple viral
      microRNAs (miRNAs) in infected cells. Here, I review our current understanding of
      how viral miRNAs influence viral replication and pathogenesis and discuss how
      viruses reshape the pattern of cellular miRNA expression. Indeed, viruses are now
      known to both activate and repress the expression of specific cellular miRNAs,
      and disrupting this process can perturb the ability of viruses to replicate
      normally. In addition, it is now clear that virally encoded miRNAs play a key
      role in inhibiting antiviral innate immune responses and can also promote cell
      transformation in culture. While our understanding of how viruses interact with
      miRNAs remains somewhat rudimentary, it is nevertheless already clear that these
      interactions can play a critical role in mediating viral pathogenesis and
      therefore may represent novel and highly specific targets for therapeutic
      intervention.

PMID- 21896653
TI  - Shared and unique properties of ubiquitin and SUMO interaction networks in DNA
      repair.
AB  - In this issue of Genes & Development, Yang and colleagues (pp. 1847-1858)
      identify new components of a small ubiquitin-like modifier (SUMO)-like
      interaction network that orchestrates and fine-tunes the Fanconi anemia (FA)
      pathway and replication-coupled repair. This new pathway emphasizes the intricate
      interplay of ubiquitin (Ub) and SUMO networks in the DNA damage response.

PMID- 21896654
TI  - Ending the message: poly(A) signals then and now.
AB  - Polyadenylation [poly(A)] signals (PAS) are a defining feature of eukaryotic
      protein-coding genes. The central sequence motif AAUAAA was identified in the mid
      1970s and subsequently shown to require flanking, auxiliary elements for both 3'
      end cleavage and polyadenylation of premessenger RNA (pre-mRNA) as well as to
      promote downstream transcriptional termination. More recent genomic analysis has
      established the generality of the PAS for eukaryotic mRNA. Evidence for the
      mechanism of mRNA 3'-end formation is outlined, as is the way this RNA processing
      reaction communicates with RNA polymerase II to terminate transcription. The
      widespread phenomenon of alternative poly(A) site usage and how this interrelates
      with pre-mRNA splicing is then reviewed. This shows that gene expression can be
      drastically affected by how the message is ended. A central theme of this review
      is that while genomic analysis provides generality for the importance of PAS
      selection, detailed mechanistic understanding still requires the direct analysis
      of specific genes by genetic and biochemical approaches.

PMID- 21896655
TI  - Transcriptional regulation of xenobiotic detoxification in Drosophila.
AB  - Living organisms, from bacteria to humans, display a coordinated transcriptional
      response to xenobiotic exposure, inducing enzymes and transporters that
      facilitate detoxification. Several transcription factors have been identified in
      vertebrates that contribute to this regulatory response. In contrast, little is
      known about this pathway in insects. Here we show that the Drosophila Nrf2 (NF-E2
      related factor 2) ortholog CncC (cap 'n' collar isoform-C) is a central regulator
      of xenobiotic detoxification responses. A binding site for CncC and its
      heterodimer partner Maf (muscle aponeurosis fibromatosis) is sufficient and
      necessary for robust transcriptional responses to three xenobiotic compounds:
      phenobarbital (PB), chlorpromazine, and caffeine. Genetic manipulations that
      alter the levels of CncC or its negative regulator, Keap1 (Kelch-like ECH
      associated protein 1), lead to predictable changes in xenobiotic-inducible gene
      expression. Transcriptional profiling studies reveal that more than half of the
      genes regulated by PB are also controlled by CncC. Consistent with these effects
      on detoxification gene expression, activation of the CncC/Keap1 pathway in
      Drosophila is sufficient to confer resistance to the lethal effects of the
      pesticide malathion. These studies establish a molecular mechanism for the
      regulation of xenobiotic detoxification in Drosophila and have implications for
      controlling insect populations and the spread of insect-borne human diseases.

PMID- 21896656
TI  - Structural basis for the role of the Sir3 AAA+ domain in silencing: interaction
      with Sir4 and unmethylated histone H3K79.
AB  - The silent information regulator 2/3/4 (Sir2/3/4) complex is required for gene
      silencing at the silent mating-type loci and at telomeres in Saccharomyces
      cerevisiae. Sir3 is closely related to the origin recognition complex 1 subunit
      and consists of an N-terminal bromo-adjacent homology (BAH) domain and a C
      terminal AAA(+) ATPase-like domain. Here, through a combination of structure
      biology and exhaustive mutagenesis, we identified unusual, silencing-specific
      features of the AAA(+) domain of Sir3. Structural analysis of the putative
      nucleotide-binding pocket in this domain reveals a shallow groove that would
      preclude nucleotide binding. Mutation of this site has little effect on Sir3
      function in vivo. In contrast, several surface regions are shown to be necessary
      for the Sir3 silencing function. Interestingly, the Sir3 AAA(+) domain is shown
      here to bind chromatin in vitro in a manner sensitive to histone H3K79
      methylation. Moreover, an exposed loop on the surface of this Sir3 domain is
      found to interact with Sir4. In summary, the unique folding of this conserved
      Sir3 AAA(+) domain generates novel surface regions that mediate Sir3-Sir4 and
      Sir3-nucleosome interactions, both being required for the proper assembly of
      heterochromatin in living cells.

PMID- 21896657
TI  - Regulation of the Fanconi anemia pathway by a SUMO-like delivery network.
AB  - The USP1/UAF1 complex deubiquitinates the Fanconi anemia protein FANCD2, thereby
      promoting homologous recombination and DNA cross-link repair. How USP1/UAF1 is
      targeted to the FANCD2/FANCI heterodimer has remained unknown. Here we show that
      UAF1 contains a tandem repeat of SUMO-like domains in its C terminus (SLD1 and
      SLD2). SLD2 binds directly to a SUMO-like domain-interacting motif (SIM) on
      FANCI. Deletion of the SLD2 sequence of UAF1 or mutation of the SIM on FANCI
      disrupts UAF1/FANCI binding and inhibits FANCD2 deubiquitination and DNA repair.
      The USP1/UAF1 complex also deubiquitinates PCNA-Ub, and deubiquitination requires
      the PCNA-binding protein hELG1. The SLD2 sequence of UAF1 binds to a SIM on
      hELG1, thus targeting the USP1/UAF1 complex to its PCNA-Ub substrate. We propose
      that the regulated targeting of USP1/UAF1 to its DNA repair substrates, FANCD2-Ub
      and PCNA-Ub, by SLD-SIM interactions coordinates homologous recombination and
      translesion DNA synthesis.

PMID- 21896658
TI  - Human SNM1A and XPF-ERCC1 collaborate to initiate DNA interstrand cross-link
      repair.
AB  - One of the major DNA interstrand cross-link (ICL) repair pathways in mammalian
      cells is coupled to replication, but the mechanistic roles of the critical
      factors involved remain largely elusive. Here, we show that purified human SNM1A
      (hSNM1A), which exhibits a 5'-3' exonuclease activity, can load from a single DNA
      nick and digest past an ICL on its substrate strand. hSNM1A-depleted cells are
      ICL-sensitive and accumulate replication-associated DNA double-strand breaks
      (DSBs), akin to ERCC1-depleted cells. These DSBs are Mus81-induced, indicating
      that replication fork cleavage by Mus81 results from the failure of the hSNM1A-
      and XPF-ERCC1-dependent ICL repair pathway. Our results reveal how collaboration
      between hSNM1A and XPF-ERCC1 is necessary to initiate ICL repair in replicating
      human cells.

PMID- 21896659
TI  - The microenvironment patterns the pluripotent mouse epiblast through paracrine
      Furin and Pace4 proteolytic activities.
AB  - The fate of pluripotent cells in early mouse embryos is controlled by graded
      Nodal signals that are activated by the endoproteases Furin and Pace4. Soluble
      forms of Furin and Pace4 cleave proNodal in vitro and after secretion in
      transfected cells, but direct evidence for paracrine activity in vivo is elusive.
      Here, we show that Furin and Pace4 are released by the extraembryonic
      microenvironment, and that they cleave a membrane-bound reporter substrate in
      adjacent epiblast cells and activate Nodal to maintain pluripotency. Secreted
      Pace4 and Furin also stimulated mesoderm formation, whereas endoderm was only
      induced by Pace4, correlating with a difference in the spatiotemporal
      distribution of these proteolytic activities. Our analysis of paracrine Furin and
      Pace4 activities and their in vivo functions significantly advances our
      understanding of how the epiblast is patterned by its microenvironment. Adding
      cell-cell communication to the pleiotropic portfolio of these proteases provides
      a new framework to study proprotein processing also in other relevant contexts.

PMID- 21896660
TI  - Practical dosimetry methods for the determination of effective skin and breast
      dose for a modern CT system, incorporating partial irradiation and prospective
      cardiac gating.
AB  - OBJECTIVE: For CT coronary angiography (CTCA), a generic chest conversion factor
      returns a significant underestimate of effective dose. The aim of this manuscript
      is to communicate new dosimetry methods to calculate weighted CT dose index
      (CTDIw), effective dose, entrance surface dose (ESD) and organ dose to the breast
      for prospectively gated CTCA. METHODS: CTDIw in 32 cm diameter Perspex phantom
      was measured using an adapted technique, accounting for the segmented scan
      characteristic. Gafchromic XRCT film (International Speciality Products, New
      Jersey, NJ) was used to measure the distribution and magnitude of ESD. Breast
      dose was measured using high sensitivity metal oxide semiconductor field-effect
      transistors and compared to the computer based imaging performance assessment of
      CT scanners (ImPACT) dosimetry calculations. RESULTS: For a typical cardiac scan
      the mean ESD remained broadly constant (7-9 mGy) when averaged over the
      circumference of the Perspex phantom. Typical absorbed dose to the breast with
      prospectively gated protocols was within the range 2-15 mGy. The subsequent
      lifetime attributable risk (LAR) of cancer incidence to the breast was found at
      0.01-0.06 for a 20-year-old female. This compares favourably to 100 mGy (LAR
      ~0.43) for a retrospectively gated CTCA. CONCLUSIONS: Care must be taken when
      considering radiation dosimetry associated with prospectively gated scanning for
      CTCA and a method has been conveyed to account for this. Breast doses for
      prospectively gated CTCA are an order of magnitude lower than retrospectively
      gated scans. Optimisation of cardiac protocols is expected to show further dose
      reduction.

PMID- 21896661
TI  - A retrospective study of the value of indirect CT venography: a British
      perspective.
AB  - OBJECTIVE: The aim of this study was to establish the value of indirect CT
      venography (CTV) in clinical practice within the UK. METHODS: 804 combined CT
      pulmonary angiogram and CTV studies were retrospectively reviewed. CTV was
      performed 180 s after the injection of contrast using an incremental technique
      with a 5-mm collimation and a 5-cm interspace between images extending from the
      iliac crests to the tibial plateaus. RESULTS: 12.9% of studies had isolated
      pulmonary emboli (PE), 3.0% had both a PE and deep vein thrombosis (DVT) and 1.1%
      had an isolated DVT. The proportion of positive cases diagnosed by CTV alone was
      6.6%. CONCLUSION: In a UK-based practice, the incidence and the proportion of
      isolated DVT diagnosed by CTV are lower than expected from published data. An
      analysis of possible causes for this is made within the paper.

PMID- 21896662
TI  - Correlation between carotid bifurcation calcium burden on non-enhanced CT and
      percentage stenosis, as confirmed by digital subtraction angiography.
AB  - OBJECTIVES: Previous evidence supports a direct relationship between the calcium
      burden (volume) on post-contrast CT with the percent internal carotid artery
      (ICA) stenosis at the carotid bifurcation. We sought to further investigate this
      relationship by comparing non-enhanced CT (NECT) and digital subtraction
      angiography (DSA). METHODS: 50 patients (aged 41-82 years) were retrospectively
      identified who had undergone cervical NECT and DSA. A 64-multidetector array CT
      (MDCT) scanner was utilised and the images reviewed using preset window
      widths/levels (30/300) optimised to calcium, with the volumes measured via three
      dimensional reconstructive software. Stenosis measurements were performed on DSA
      and luminal diameter stenoses >40% were considered "significant". Volume
      thresholds of 0.01, 0.03, 0.06, 0.09 and 0.12 cm(3) were utilised and Pearson'S
      correlation coefficient (r) was calculated to correlate the calcium volume with
      percent stenosis. RESULTS: Of 100 carotid bifurcations, 88 were available and of
      these 7 were significantly stenotic. The NECT calcium volume moderately
      correlated with percent stenosis on DSA r=0.53 (p<0.01). A moderate-strong
      correlation was found between the square root of calcium volume on NECT with
      percent stenosis on DSA (r=0.60, p<0.01). Via a receiver operating characteristic
      curve, 0.06 cm(3) was determined to be the best threshold (sensitivity 100%,
      specificity 90.1%, negative predictive value 100% and positive predictive value
      46.7%) for detecting significant stenoses. CONCLUSION: This preliminary
      investigation confirms a correlation between carotid bifurcation calcium volume
      and percent ICA stenosis and is promising for the optimal threshold for stenosis
      detection. Future studies could utilise calcium volumes to create a "score" that
      could predict high grade stenosis.

PMID- 21896663
TI  - MRI findings of mucoepidermoid carcinoma of the parotid gland: correlation with
      pathological features.
AB  - OBJECTIVE: The aim of this study was to correlate the MRI appearance and
      pathological findings in each grade of the mucoepidermoid carcinoma (MEC) of the
      parotid gland. METHODS: We reviewed surgically proven MECs of parotid glands in
      20 patients. Pathologically, 5 tumours were high-grade, 3 were intermediate and
      12 were low-grade. MR images were evaluated with emphasis on signal intensities
      on T(2) weighted images, margin characteristics and lymph node metastasis,
      correlating these with pathological features. RESULTS: Among the high-grade MECs,
      four out of five tumours showed inhomogeneous low to intermediate signal
      intensity on T(2) weighted images, reflecting high cellularity. All tumours had
      an ill-defined margin, reflecting invasive tumour growth. Among the intermediate
      grade MECs, all three tumours showed intermediate signal intensity on T(2)
      weighted images and two tumours had an ill-defined margin. Among the low-grade
      MECs, 11 of the 12 tumours had a hyperintense area on T(2) weighted images
      because of the existence of abundant mucin secreting cells. Seven tumours had an
      ill-defined margin, reflecting peritumoural inflammatory changes rather than
      invasive tumour growth. Lymph node metastasis was seen in three high-grade MECs.
      CONCLUSION: MECs of the parotid gland show variable MRI findings reflecting their
      histological nature, which seems to have certain tendencies depending on the
      tumour grade.

PMID- 21896664
TI  - Diffusion-weighted imaging in the assessment of tumour grade in endometrial
      cancer.
AB  - OBJECTIVE: Endometrial cancer is the most common gynaecological malignancy in
      developed countries. Histological grade and subtype are important prognostic
      factors obtained by pipelle biopsy. However, pipelle biopsy "samples" tissue and
      a high-grade component that requires more aggressive treatment may be missed. The
      purpose of the study was to assess the use of diffusion-weighted MRI (DW-MRI) in
      the assessment of tumour grade in endometrial lesions. METHOD: 42 endometrial
      lesions including 23 endometrial cancers and 19 benign lesions were evaluated
      with DW-MRI (1.5T with multiple b-values between 0 and 750 s mm(-2)). Visual
      evaluation and the calculation of mean and minimum apparent diffusion coefficient
      (ADC) value were performed and correlated with histology. RESULTS: The mean and
      minimum ADC values for each histological grade were 1.02 +/- 0.29*10(-3) mm(2) s(
      1) and 0.74 +/- 0.24*10(-3) mm(2) s(-1) (grade 1), 0.88 +/- 0.39*10(-3) mm(2) s(
      1) and 0.64 +/- 0.36*10(-3) mm(2) s(-1) (grade 2), and 0.94 +/- 0.32*10(-3) mm(2)
      s(-1) and 0.72 +/- 0.36*10(-3) mm(2) s(-1) (grade 3), respectively. There was no
      statistically significant difference between tumour grades. However, the mean ADC
      value for endometrial carcinoma was 0.97 +/- 0.31, which was significantly lower
      (p<0.0001) than that of benign endometrial pathology (1.50 +/- 0.14). Applying a
      cut-off mean ADC value of less than 1.28 * 10(-3) mm(2) s(-1)we obtained a
      sensitivity, specificity, positive predictive value and negative predictive value
      for malignancy of 87%, 100%, 100% and 85.7%, respectively. CONCLUSION: Tumour
      mean and minimum ADC values are not useful in differentiating histological tumour
      grade in endometrial carcinoma. However, mean ADC measurement can provide useful
      information in differentiating benign from malignant endometrial lesions. This
      information could be clinically relevant in those patients where pre-operative
      endometrial sampling is not possible.

PMID- 21896665
TI  - Evaluation of virtual unenhanced CT obtained from dual-energy CT urography for
      detecting urinary stones.
AB  - OBJECTIVE: The aim of our study was to determine if virtual unenhanced CT (VUCT)
      is equivalent to unenhanced CT (UCT) for detecting urinary stones. METHODS: Our
      institutional review board approved this retrospective study, which was compliant
      with the Health Insurance Portability and Accountability Act. A total of 80
      stones were detected in 32 patients among 146 consecutive patients undergoing
      dual-energy CT urography. The number and size of stones were recorded on
      nephrographic VUCT (NVUCT) and excretory VUCT (EVUCT) images, respectively. UCT
      was a reference of standard for the number and size of stones. Image quality of
      VUCT was qualitatively assessed using a five-point scale. Repeated-measures
      analysis of variance with post-test was used for statistical analysis. RESULTS:
      62 stones in 29 patients were detected on NVUCT and 59 stones in 27 patients were
      detected on EVUCT. The size of stones detected on NVUCT or EVUCT was
      significantly smaller compared with stones on UCT (p<0.05). The size of stones
      detected on UCT, NVUCT and EVUCT ranged from 1.4 to 19.2 mm (mean, 4.6 mm), 0 to
      19.2 mm (mean, 3.6 mm) and 0 to 18.7 mm (mean, 3.6 mm), respectively. 18 stones
      were missed on NVUCT and 21 were missed on EVUCT. The sizes ranged from 1.4 to
      3.2 mm (mean, 2.1 mm) and 1.4 to 3.2 mm (mean, 2.2 mm) on UCT, respectively. VUCT
      was inferior to UCT regarding image quality (p<0.05). CONCLUSION: VUCT missed a
      significant number of small stones probably owing to poor image quality compared
      with UCT. Subsequently, VUCT cannot replace UCT for detecting urinary stones.

PMID- 21896666
TI  - Diffusion tensor imaging of normal prostate at 3 T: effect of number of diffusion
      encoding directions on quantitation and image quality.
AB  - OBJECTIVE: The purpose of this study was to prospectively investigate differences
      of diffusion tensor imaging (DTI) using a different number of diffusion-encoding
      directions and to evaluate the feasibility of tractography in healthy prostate at
      3 T. METHOD: 12 healthy volunteers underwent DTI with single-shot echo-planar
      imaging at 3 T using a phased-array coil. Diffusion gradients of each DTI were
      applied in 6 (Group 1), 15 (Group 2) and 32 (Group 3) non-collinear directions.
      For each group, the mean apparent diffusion coefficient (ADC), fractional
      anisotrophy (FA) and signal-to-noise ratio (SNR) were measured in the peripheral
      zone (PZ) and central gland (CG). The quality of diffusion-weighted and
      tractographic images were also evaluated. RESULTS: In all three groups, the mean
      ADC value of the CG was statistically lower than that of the PZ (p<0.01) and the
      mean FA value of the CG was statistically greater than that of the PZ (p<0.01).
      For the mean FA value of the CG, no statistical difference was seen among the
      three groups (p=0.052). However, the mean FA value of the PZ showed a statistical
      difference among the three groups (p=0.035). No significant difference in SNR
      values was seen among the three groups (p>0.05). Imaging quality of diffusion
      weighted tractographic images was rated as satisfactory or better in all three
      groups and was similar among the three groups. CONCLUSION: In conclusion,
      prostate DTI at 3 T was feasible with different numbers of diffusion-encoding
      directions. The number of diffusion-encoding directions did not have a
      significant effect on imaging quality.

PMID- 21896667
TI  - Development of a primary care physician task list to evaluate clinic visit
      workflow.
AB  - BACKGROUND: Interventions designed to improve the delivery of primary care,
      including Patient-Centered Medical Homes and electronic health records, require
      an understanding of clinical workflow to be successfully implemented. However,
      there is a lack of tools to describe and study primary care physician workflow.
      We developed a comprehensive list of primary care physician tasks that occur
      during a face-to-face patient visit. METHODS: A validated list of tasks performed
      by primary care physicians during patient clinic visits was developed from a
      secondary data analysis of observation data from two studies evaluating primary
      care workflow. Thirty primary care physicians participated from a convenience
      sample of 17 internal medicine and family medicine clinics in Wisconsin and Iowa
      across rural and urban settings and community and academic settings. RESULTS: The
      final task list has 12 major tasks, 189 subtasks, and 191 total tasks. The major
      tasks are: Enter Room, Gather Information from Patient, Review Patient
      Information, Document Patient Information, Perform, Recommend / Discuss Treatment
      Options, Look Up, Order, Communicate, Print / Give Patient (advice,
      instructions), Appointment Wrap-up, and Leave Room. Additional subcodes note use
      of paper or EHR and the presence of a caregiver or medical student. CONCLUSIONS:
      The task list presented here is a tool that will help clinics study their
      workflows so they can plan for changes that will take place because of EHR
      implementation and/or transformation to a patient centered medical home.

PMID- 21896668
TI  - PTH ablation ameliorates the anomalies of Fgf23-deficient mice by suppressing the
      elevated vitamin D and calcium levels.
AB  - Fibroblast growth factor 23 (FGF23) is a key regulator of mineral ion
      homeostasis. Genetic ablation of Fgf23 in mice leads to severe biochemical
      disorders including elevated serum 1,25-dihydroxyvitamin D [1,25(OH)2D],
      hypercalcemia, hyperphosphatemia, and marked decreased PTH levels. Because PTH
      stimulates 1,25(OH)2D production and increases serum calcium levels, we
      hypothesized that ablation of PTH from the Fgf23 knockout (Fgf23-/-) mice could
      suppress these affects, thus ameliorating the soft tissue and skeletal anomalies
      in these animals. In this study, we generated a genetic mouse model with dual
      ablation of the Fgf23/PTH genes. The data show that deletion of PTH does suppress
      the markedly higher serum 1,25(OH)2D and calcium levels observed in Fgf23-/- mice
      and results in much larger, heavier, and more active double-knockout mice with
      improved soft tissue and skeletal phenotypes. On the contrary, when we infused
      PTH (1-34) peptide into Fgf23-/- mice using osmotic minipumps, serum 1,25(OH)2D
      and calcium levels were increased even further, leading to marked reduction in
      trabecular bone. These results indicate that PTH is able to modulate the
      anomalies of Fgf23-/- mice by controlling serum 1,25(OH)2D and calcium levels.

PMID- 21896669
TI  - Diacerhein improves glucose tolerance and insulin sensitivity in mice on a high
      fat diet.
AB  - Obesity and type 2 diabetes are characterized by insulin resistance, and the
      common basis of these events is a chronic and systemic inflammatory process
      marked by the activation of the c-Jun N-terminal kinase (JNK) and inhibitor
      kappaB kinase (IKKbeta)/nuclear factor-kappaB (NFkappaB) pathways, up-regulated
      cytokine synthesis, and endoplasmic reticulum dysfunction. The aim of this study
      was to evaluate the effects of diacerhein administration, an antiinflammatory
      drug that reduces the levels of inflammatory cytokines, on insulin sensitivity
      and signaling in diet-induced obese (DIO) mice. Swiss mice were fed with
      conventional chow (control group) or a high-fat diet (DIO group). Later, DIO mice
      were randomly subdivided into a new subgroup (DAR) that received 20 mg/kg
      diacerhein for 10 d. Western blotting was used to quantify the expression and
      phosphorylation of insulin receptor, insulin receptor substrate 1, and Akt and of
      inflammatory mediators that modulate insulin signaling in a negative manner
      (IKKbeta, JNK, and inducible nitric oxide synthase). We show here, for the first
      time, that the administration of diacerhein in DIO mice improved endoplasmic
      reticulum stress, reduced JNK and IKKbeta phosphorylation, and resulted in a
      marked improvement in fasting glucose, a decrease in macrophage infiltration in
      adipose tissue, and a reduced expression and activity of proinflammatory
      mediators accompanied by an improvement in the insulin signaling mainly in the
      liver and adipose tissue. Taken together, these results indicate that diacerhein
      treatment improves insulin sensitivity in obesity, mediated by the reversal of
      subclinical inflammation, and that this drug may be an alternative therapy for
      insulin resistance.

PMID- 21896670
TI  - The PACAP-regulated gene selenoprotein T is highly induced in nervous, endocrine,
      and metabolic tissues during ontogenetic and regenerative processes.
AB  - Selenoproteins contain the essential trace element selenium whose deficiency
      leads to major disorders including cancer, male reproductive system failure, or
      autoimmune thyroid disease. Up to now, 25 selenoprotein-encoding genes were
      identified in mammals, but the spatiotemporal distribution, regulation, and
      function of some of these selenium-containing proteins remain poorly documented.
      Here, we found that selenoprotein T (SelT), a new thioredoxin-like protein, is
      regulated by the trophic neuropeptide pituitary adenylate cyclase-activating
      polypeptide (PACAP) in differentiating but not mature adrenomedullary cells. In
      fact, our analysis revealed that, in rat, SelT is highly expressed in most
      embryonic structures, and then its levels decreased progressively as these organs
      develop, to vanish in most adult tissues. In the brain, SelT was abundantly
      expressed in neural progenitors in various regions such as the cortex and
      cerebellum but was undetectable in adult nervous cells except rostral migratory
      stream astrocytes and Bergmann cells. In contrast, SelT expression was maintained
      in several adult endocrine tissues such as pituitary, thyroid, or testis. In the
      pituitary gland, SelT was found in secretory cells of the anterior lobe, whereas
      in the testis, the selenoprotein was present only in spermatogenic and Leydig
      cells. Finally, we found that SelT expression is strongly stimulated in liver
      cells during the regenerative process that occurs after partial hepatectomy.
      Taken together, these data show that SelT induction is associated with
      ontogenesis, tissue maturation, and regenerative mechanisms, indicating that this
      PACAP-regulated selenoprotein may play a crucial role in cell growth and activity
      in nervous, endocrine, and metabolic tissues.

PMID- 21896671
TI  - Prevention of the onset of ovarian hyperstimulation syndrome (OHSS) in the rat
      after ovulation induction with a low molecular weight agonist of the LH receptor
      compared with hCG and rec-LH.
AB  - Ovarian hyperstimulation syndrome (OHSS) incidentally occurs in controlled
      ovarian stimulation protocols and is associated with human chorionic gonadotropin
      (hCG) administration. OHSS is caused by increased vascular permeability (VP) and
      thought to be mediated by hypersecretion of vascular endothelial growth factor
      (VEGF) by granulosa cells. Low molecular weight (LMW)-LH agonists have a similar
      mode of action but a shorter half-life compared with hCG, which could potentially
      lead to a clinical benefit in reducing the risk for OHSS in controlled ovarian
      stimulation protocols. The objective of this study is to investigate the role of
      an orally active LMW-LH agonist in OHSS induction compared with recombinant LH
      (rec-LH) and hCG. Immature rats were hyperstimulated with pregnant mare serum
      gonadotropin, and ovulation was induced by hCG, rec-LH or a LMW-LH agonist. The
      degree of VP was determined by Evans Blue in the abdominal cavity. Ovaries were
      weighed, and VEGF concentration in the ovary was determined. Pregnant mare serum
      gonadotropin stimulation followed by single-dose hCG or rec-LH resulted in clear
      enlargement of the ovaries and increased VP and VEGF levels. However, ovulation
      induction with a single dose of the LMW-LH agonist did not result in increased VP
      and VEGF levels, and even multiple dosing to mimic a longer exposure did not
      induce OHSS symptoms. In conclusion, we demonstrated that the oral LMW-LH agonist
      did not induce VP in rat, indicative for OHSS, possibly due to reduced VEGF
      production. If this is translatable to human, this could potentially represent a
      clinical benefit in reducing the risk for OHSS when using these compounds in
      controlled ovarian stimulation protocols.

PMID- 21896672
TI  - Colocalization of FM1-43, Bassoon, and GnRH-1: GnRH-1 release from cell bodies
      and their neuroprocesses.
AB  - Pulsatile release of GnRH-1 is critical for reproductive function. However, the
      cellular mechanism of GnRH-1 neurosecretion is still elusive. In this study, we
      examined the neurosecretory process of GnRH-1 neurons using time-lapse image
      acquisition followed by immunocytochemistry with confocal microscopy. To monitor
      exocytotic processes, cultured GnRH-1 neurons derived from monkey embryos were
      labeled with the lipophilic dye, FM1-43, or its fixable form FM1-43Fx, in the
      presence or absence of depolarization signals, and changes in vesicles labeled
      with FM1-43 were analyzed. The results show FM1-43 was taken up into the cell and
      labeled puncta in the soma and neuroprocesses in the absence of depolarization
      signals, indicating that GnRH-1 neurons were spontaneously active. Depolarization
      of GnRH-1 neurons with high K+ or veratridine challenge increased the intensity
      and size of puncta in both soma and neuroprocesses, and the veratridine-induced
      changes in puncta were blocked by tetrodotoxin, indicating that changes in the
      puncta intensity and size reflect neurosecretory activity. Subsequent double
      immunocytochemistry for GnRH-1 and the synaptic vesicle marker, vesicle
      associated membrane protein, demonstrated that the FM1-43Fx-labeled puncta were
      synaptic vesicles with the GnRH-1 peptide. Additional double immunocytochemistry
      for GnRH-1 and the marker of the neurosecretory active zone, Bassoon, indicated
      that the FM1-43Fx-labeled puncta were located at the sites of neurosecretory
      active zones in GnRH-1 neurons. These results suggest that GnRH-1 neurons have
      the capacity to release the peptide from the soma and dendrites. Collectively, we
      hypothesize that soma-dendritic release of the peptide may be a mechanism of
      synchronized activity among GnRH-1 neurons.

PMID- 21896673
TI  - Genome-wide association study of HPV seropositivity.
AB  - High-risk alpha mucosal types of human papillomavirus (HPV) cause anogenital and
      oropharyngeal cancers, whereas beta cutaneous HPV types (e.g. HPV8) have been
      implicated in non-melanoma skin cancer. Although antibodies against the capsid
      protein L1 of HPV are considered as markers of cumulative exposure, not all
      infected persons seroconvert. To identify common genetic variants that influence
      HPV seroconversion, we performed a two-stage genome-wide association study.
      Genome-wide genotyping of 316 015 single nucleotide polymorphisms was carried out
      using the Illumina HumanHap300 BeadChip in 4811 subjects from a central European
      case-control study of lung, head and neck and kidney cancer that had serology
      data available on 13 HPV types. Only one association met genome-wide significance
      criteria, namely that between HPV8 seropositivity and rs9357152 [odds ratio (OR)
      = 1.37, 95% confidence interval (CI) = 1.24-1.50 for the minor allele G; P=1.2 *
      10(-10)], a common genetic variant (minor allele frequency=0.33) located within
      the major histocompatibility complex (MHC) II region at 6p21.32. This association
      was subsequently replicated in an independent set of 2344 subjects from a Latin
      American case-control study of head and neck cancer (OR=1.35, 95% CI=1.18-1.56,
      P=2.2 * 10(-5)), yielding P=1.3 * 10(-14) in the combined analysis (P
      heterogeneity=0.87). No heterogeneity was noted by cancer status (controls/lung
      cancer cases/head and neck cancer cases/kidney cancer cases). This study provides
      a proof of principle that genetic variation plays a role in antibody reactivity
      to HPV infection.

PMID- 21896674
TI  - A rare malposition of the central venous catheter.

PMID- 21896675
TI  - Temporary transvenous pacing: endangered skill.
AB  - BACKGROUND: Temporary cardiac pacing although is an essential requirement for
      core medical training (CMT) in UK, there are no defined training measures and
      guidelines available as to who should perform this. METHODS: We conducted an
      anonymous survey of 300 non-cardiology medical registrars regarding their
      individual ability, experience and training received in temporary pacing wire
      (TPW) insertion. RESULTS: A total of 202 (67%) responses were received. 61% (123)
      had not performed any TPW insertion before becoming a registrar. Only 18% (38)
      felt confident in inserting a TPW unsupervised and only 14 (7%) had ever received
      any formal training. The majority, 169 (84%), did not feel that their on-call
      consultant general physician would be able to perform the procedure. CONCLUSION:
      This survey shows that general medical registrars lack a major life-saving skill
      that is required as part of CMT. Thus, there is now an urgent clinical governance
      need to either formally train physicians or abandon the concept and practice of
      general internal medicine-led temporary pacing, and devolve this to
      cardiologists.

PMID- 21896676
TI  - A physiotherapy service to an emergency extended care unit does not decrease
      admission rates to hospital: a randomised trial.
AB  - BACKGROUND: One of the reasons physiotherapy services are provided to emergency
      departments (EDs) and emergency extended care units (EECUs) is to review
      patients' mobility to ensure they are safe to be discharged home. AIM: To
      investigate whether a physiotherapy service to an EECU altered the rate of
      hospital admission, rate of re-presentation to the ED, visits to community
      healthcare practitioners, return to usual work/home/leisure activities and
      patient satisfaction. METHODS: A randomised trial with concealed allocation,
      assessor blinding and intention-to-treat analysis was undertaken in an EECU. The
      sample comprised 186 patients (mean age 70 years, 123 (66%) female patients, 130
      (70%) trauma) who were referred for physiotherapy assessment/intervention.
      Referral occurred at any stage of the patients' EECU admission. All participants
      received medical/nursing care as required. The physiotherapy group also received
      physiotherapy assessment/intervention. RESULTS: The physiotherapy group had a 4%
      (95% CI -18% to 9%) lower rate of admission to hospital than the control group
      and a 4% (95% CI -6% to 13%) higher rate of re-presentation to the ED, which were
      statistically non-significant (p>=0.45). Differences between groups for use of
      community healthcare resources, return to usual work/home/leisure activities and
      satisfaction with their EECU care were small and not significant. CONCLUSION: A
      physiotherapy service for EECU patients, as provided in this study, did not
      reduce the rate of hospital admission, rate of re-presentation to the ED, use of
      community healthcare resources, or improve the rate of return to usual
      work/home/leisure activities or patient satisfaction. Trial registration number
      ANZCTRN12609000106235.

PMID- 21896677
TI  - Conversion of commensal Escherichia coli K-12 to an invasive form via expression
      of a mutant histone-like protein.
AB  - The HUalpha(E38K, V42L) mutant of the bacterial histone-like protein HU causes a
      major change in the transcription profile of the commensal organism Escherichia
      coli K-12 (Kar S, Edgar R, Adhya S, Proc. Natl. Acad. Sci. U. S. A. 102:16397
      16402, 2005). Among the upregulated genes are several related to pathogenic
      interactions with mammalian cells, as evidenced by the expression of curli
      fibers, Ivy, and hemolysin E. When E. coli K-12/ HUalpha(E38K, V42L) was added to
      Int-407 cells, there was host cell invasion, phagosomal disruption, and
      intracellular replication. The invasive trait was also retained in a murine ileal
      loop model and intestinal explant assays. In addition to invasion, the
      internalized bacteria caused a novel subversion of host cell apoptosis through
      modification and regulation of the BH3-only proteins Bim(EL) and Puma. Changes in
      the transcription profile were attributed to positive supercoiling of DNA leading
      to the altered availability of relevant promoters. Using the E. coli K
      12/HUalpha(E38K, V42L) variant as a model, we propose that traditional commensal
      E. coli can adopt an invasive lifestyle through reprogramming its cellular
      transcription, without gross genetic changes. IMPORTANCE: Escherichia coli K-12
      is well established as a benign laboratory strain and a human intestinal
      commensal. Recent evidences, however, indicate that the typical noninvasive
      nature of resident E. coli can be reversed under specific circumstances even in
      the absence of any major genomic flux. We previously engineered an E. coli strain
      with a mutant histone-like protein, HU, which exhibited significant changes in
      nucleoid organization and global transcription. Here we showed that the changes
      induced by the mutant HU have critical functional consequences: from a strict
      extracellular existence, the mutant E. coli adopts an almost obligate
      intracellular lifestyle. The internalized E. coli exhibits many of the
      prototypical characteristics of traditional intracellular bacteria, like
      phagosomal escape, intracellular replication, and subversion of host cell
      apoptosis. We suggest that E. coli K-12 can switch between widely divergent
      lifestyles in relation to mammalian host cells by reprogramming its cellular
      transcription program and without gross changes in its genomic content.

PMID- 21896678
TI  - Conserved mutations in the pneumococcal bacteriocin transporter gene, blpA,
      result in a complex population consisting of producers and cheaters.
AB  - All fully sequenced strains of Streptococcus pneumoniae possess a version of the
      blp locus, which is responsible for bacteriocin production and immunity.
      Activation of the blp locus is stimulated by accumulation of the peptide
      pheromone, BlpC, following its secretion by the ABC transporter, BlpA. The blp
      locus is characterized by significant diversity in blpC type and in the region of
      the locus containing putative bacteriocin and immunity genes. In addition, the
      blpA gene can represent a single large open reading frame or be divided into
      several smaller fragments due to the presence of frameshift mutations. In this
      study, we use a collection of strains with blp-dependent inhibition and immunity
      to define the genetic changes that bring about phenotypic differences in
      bacteriocin production or immunity. We demonstrate that alterations in blpA,
      blpC, and bacteriocin/immunity content likely play an important role in
      competitive interactions between pneumococcal strains. Importantly, strains with
      a highly conserved frameshift mutation in blpA are unable to secrete bacteriocins
      or BlpC, but retain the ability to respond to exogenous peptide pheromone
      produced by cocolonizing strains, stimulating blp-mediated immunity. These
      "cheater" strains can only coexist with bacteriocin-producing strains that
      secrete their cognate BlpC and share the same immunity proteins. The variable
      outcome of these interactions helps to explain the heterogeneity of the blp
      pheromone, bacteriocin, and immunity protein content. IMPORTANCE: Streptococcus
      pneumoniae resides in a polymicrobial environment and competes for limited
      resources by the elaboration of small antimicrobial peptides called bacteriocins.
      A conserved cluster of genes in the S. pneumoniae genome is involved in the
      production of bacteriocins and their associated protective immunity proteins
      through secretion of a signaling pheromone. In this study, we show that a
      significant number of strains have lost the ability to secrete bacteriocins and
      signaling pheromones due to a specific mutation in a dedicated transporter
      protein. Because the regulatory and immunity portion of the locus is retained,
      these "cheater" strains can survive in the face of invasion from a bacteriocin
      producing strain without the cost of bacteriocin secretion. The outcome of such
      interactions depends on each strain's repertoire of pheromone, immunity protein,
      and bacteriocin genes, such that intrastrain competition drives the diversity in
      bacteriocin, immunity protein, and pheromone content.

PMID- 21896679
TI  - H5N1 influenza virus pathogenesis in genetically diverse mice is mediated at the
      level of viral load.
AB  - The genotype of the host is one of several factors involved in the pathogenesis
      of an infectious disease and may be a key parameter in the epidemiology of highly
      pathogenic H5N1 influenza virus infection in humans. Gene polymorphisms may
      affect the viral replication rate or alter the host's immune response to the
      virus. In humans, it is unclear which aspect dictates the severity of H5N1 virus
      disease. To identify the mechanism underlying differential responses to H5N1
      virus infection in a genetically diverse population, we assessed the host
      responses and lung viral loads in 21 inbred mouse strains upon intranasal
      inoculation with A/Hong Kong/213/03 (H5N1). Resistant mouse strains survived
      large inocula while susceptible strains succumbed to infection with 1,000- to
      10,000-fold-lower doses. Quantitative analysis of the viral load after
      inoculation with an intermediate dose found significant associations with
      lethality as early as 2 days postinoculation, earlier than any other disease
      indicator. The increased viral titers in the highly susceptible strains mediated
      a hyperinflamed environment, indicated by the distinct expression profiles and
      increased production of inflammatory mediators on day 3. Supporting the
      hypothesis that viral load rather than an inappropriate response to the virus was
      the key severity-determining factor, we performed quantitative real-time PCR
      measuring the cytokine/viral RNA ratio. No significant differences between
      susceptible and resistant mouse strains were detected, confirming that it is the
      host genetic component controlling viral load, and therefore replication
      dynamics, that is primarily responsible for a host's susceptibility to a given
      H5N1 virus. IMPORTANCE: Highly pathogenic H5N1 influenza virus has circulated in
      Southeast Asia since 2003 but has been confirmed in relatively few individuals.
      It has been postulated that host genetic polymorphisms increase the
      susceptibility to infection and severe disease. The mechanisms and host proteins
      affected during severe disease are unknown. Inbred mouse strains vary
      considerably in their ability to resist H5N1 virus and were used to identify the
      primary mechanism determining disease severity. After inoculation with H5N1,
      resistant mouse strains had reduced amounts of virus in their lungs, which
      subsequently resulted in lower production of proinflammatory mediators and less
      pathology. We therefore conclude that the host genetic component controlling
      disease severity is primarily influencing viral replication. This is an important
      concept, as it emphasizes the need to limit virus replication through antiviral
      therapies and it shows that the hyperinflammatory environment is simply a
      reflection of more viral genetic material inducing a response.

PMID- 21896682
TI  - The Roy L. Whistler International Award in Carbohydrate Chemistry 2012.

PMID- 21896680
TI  - Antimicrobial actions of reactive oxygen species.
AB  - Reactive oxygen species (ROS) are produced by host phagocytes and exert
      antimicrobial actions against a broad range of pathogens. The observable
      antimicrobial actions of ROS are highly dependent on experimental conditions.
      This perspective reviews recent controversies regarding ROS in Salmonella
      phagocyte interactions and attempts to reconcile conflicting observations from
      different laboratories.

PMID- 21896683
TI  - Policy brief.

PMID- 21896684
TI  - Childhood health and labor market inequality over the life course.
AB  - The authors use data from the Health and Retirement Study's Earnings Benefit
      File, which links Health and Retirement Study to Social Security Administration
      records, to estimate the impact of childhood health on earnings curves between
      the ages of 25 and 50 years. They also investigate the extent to which diminished
      educational attainment, earlier onset of chronic health conditions, and labor
      force participation mediate this relationship. Those who experience poor
      childhood health have substantially diminished labor market earnings over the
      work career. For men, earnings differentials grow larger over the early to middle
      career and then slow down and begin to converge as they near 50 years of age. For
      women, earnings differentials emerge later in the career and show no evidence of
      convergence. Part of the child health earnings differential is accounted for by
      selection into diminished educational attainment, the earlier onset of chronic
      disease in adulthood, and, particularly for men, labor force participation.

PMID- 21896685
TI  - Maternal depression and childhood health inequalities.
AB  - An increasing body of literature documents considerable inequalities in the
      health of young children in the United States, though maternal depression is one
      important, yet often overlooked, determinant of children's health. In this
      article, the author uses data from the Fragile Families and Child Wellbeing Study
      (N = 4,048) and finds that maternal depression, particularly recurrent or chronic
      depression, puts children at risk of having unfavorable health when they are five
      years old. This finding persists despite adjusting for a host of demographic
      characteristics of the mothers and children (including children's prior health)
      and is consistent across multiple health outcomes. Family instability, maternal
      health, and socioeconomic status account for the association between maternal
      depression and children's health. Given that poor childhood health may lead to
      poor health and low socioeconomic status in adulthood, maternal depression may
      contribute to the intergenerational transmission of inequality.

PMID- 21896686
TI  - Dynamics of inequality: mother's education and infant mortality in China, 1970
      2001.
AB  - In this study, the authors analyze the dynamic relationship between Chinese
      women's education, their utilization of newly available medical pregnancy care,
      and their infants' mortality risk. China has undergone enormous social, economic,
      and political changes over recent decades and is a novel context in which to
      examine the potential influence of social change and technological innovation on
      health disparities. The authors consider efficacy, or the ability to quickly
      absorb and effectively utilize new medical innovations, and argue that the social
      stratification of efficacy provides an important conceptual link between
      education and the greater likelihood of benefitting from medical innovations.
      Using the 2001 National Family Planning and Reproductive Health Survey data and
      multilevel, multiprocess models, the authors show that Chinese infants born to
      better educated mothers retained a survival advantage over the turbulent decades
      between 1970 and 2000. This occurs largely because educated mothers more actively
      sought prenatal care and professional delivery assistance use.

PMID- 21896687
TI  - Is discrimination an equal opportunity risk?: racial experiences, socioeconomic
      status, and health status among black and white adults.
AB  - Using the 2004 Behavioral Risk Factor Surveillance System, we explore the
      relationship between racial awareness, perceived discrimination, and self-rated
      health among black (n = 5,902) and white (n = 28,451) adults. We find that
      adjusting for group differences in racial awareness and discrimination, in
      addition to socioeconomic status, explains the black-white gap in self-rated
      health. However, logistic regression models also find evidence for differential
      vulnerability among black and whites adults, based on socioeconomic status. While
      both groups are equally harmed by emotional and/or physical reactions to race
      based treatment, the negative consequences of discriminatory experiences for
      black adults are exacerbated by their poorer socioeconomic standing. In contrast,
      the association between racial awareness and self-rated health is more sensitive
      to socioeconomic standing among whites. Poorer health is more likely to occur
      among whites when they reflect at least daily on their own racial status-but only
      when it happens in tandem with mid-range educational achievement, or among
      homemakers.

PMID- 21896688
TI  - Gender and physical health: a study of African American and Caribbean black
      adults.
AB  - Although gender disparities in health in the United States remain a primary
      concern among health professionals, less is known about this phenomenon within
      the black American population. Using the National Survey of American Life, the
      author examines gender differences in self-rated health, chronic illness, and
      functional limitations among African Americans (n = 3,330) and Caribbean blacks
      (n = 1,562) and the extent to which the availability of resources explains these
      differences. The results reveal a consistent disadvantage among African American
      women across indicators of health. The gender-health relationship among Caribbean
      blacks is somewhat weaker, but there is a health disadvantage for immigrant women
      and U.S.-born Caribbean men when certain resources are taken into account. These
      findings illustrate the importance of the intersections of race, ethnicity, and
      nativity in our understanding of gender differences in health.

PMID- 21896689
TI  - Persistent fever in an infant: incomplete Kawasaki disease.

PMID- 21896690
TI  - Mesial temporal sclerosis in epilepsy.

PMID- 21896691
TI  - Provincial squeeze on generic prices continues.

PMID- 21896692
TI  - iPhone app an aid in diagnosing concussions.

PMID- 21896693
TI  - A pack a day: just what the doctor ordered?

PMID- 21896694
TI  - Value of e-prescribing questioned.

PMID- 21896695
TI  - [Albiny Paquette].

PMID- 21896696
TI  - WHO reforms long overdue, critics say.

PMID- 21896698
TI  - Use of nonaspirin nonsteroidal anti-inflammatory drugs during pregnancy and the
      risk of spontaneous abortion.
AB  - BACKGROUND: The association between the use of nonaspirin nonsteroidal anti
      inflammatory drugs (NSAIDs) during pregnancy and the risk of spontaneous abortion
      remains unclear because of inconsistent research results and the lack of evidence
      for an effect due to specific types or dosages of nonaspirin NSAIDs. We aimed to
      quantify the association between having a spontaneous abortion and types and
      dosages of nonaspirin NSAIDs in a cohort of pregnant women. METHODS: Using a
      nested case-control design, we obtained data from the Quebec Pregnancy Registry
      for 4705 women who had a spontaneous abortion. For each instance, we randomly
      selected 10 controls from the remaining women in the registry who were matched by
      index date (date of the spontaneous abortion) and gestational age. Use of
      nonaspirin NSAIDs (identified by filled prescriptions) and nonuse were compared.
      We also looked for associations between different types and dosages of nonaspirin
      NSAIDs and having a spontaneous abortion. Analyses of associations and adjustment
      for confounding were done using conditional logistic regression. RESULTS: We
      identified 4705 cases of spontaneous abortion (352 exposed [7.5%]); 47 050
      controls (1213 exposed [2.6%]). Adjusting for potential confounders, the use of
      nonaspirin NSAIDs during pregnancy was significantly associated with the risk of
      spontaneous abortion (odds ratio [OR] 2.43, 95% confidence interval [CI] 2.12
      2.79). Specifically, use of diclofenac (OR 3.09, 95% CI 1.96-4.87), naproxen (OR
      2.64, 95% CI 2.13-3.28), celecoxib (OR 2.21, 95% CI 1.42-3.45), ibuprofen (OR
      2.19, 95% CI 1.61-2.96) and rofecoxib (OR 1.83, 95% CI 1.24-2.70) alone, and
      combinations thereof (OR 2.64, 95% CI 1.59-4.39), were all associated with
      increased risk of spontaneous abortion. No dose-response effect was seen.
      INTERPRETATION: Gestational exposure to any type or dosage of nonaspirin NSAIDs
      may increase the risk of spontaneous abortion. These drugs should be used with
      caution during pregnancy.

PMID- 21896699
TI  - Acute hepatitis associated with autochthonous hepatitis E virus infection--San
      Antonio, Texas, 2009.
AB  - Locally acquired hepatitis E infection is increasingly being observed in
      industrialized countries. We report 2 cases of autochthonous acute hepatitis E in
      the United States. Hepatitis E virus genotype 3a related to US-2 and swine
      hepatitis E virus strains was isolated from one of the patients, indicating
      potential food-borne or zoonotic transmission.

PMID- 21896700
TI  - Initial recovery and rebound of type f intestinal colonization botulism after
      administration of investigational heptavalent botulinum antitoxin.
AB  - Investigational heptavalent botulinum antitoxin (HBAT) is now the primary
      antitoxin for US noninfant botulism patients. HBAT consists of equine Fab/F(ab')2
      IgG fragments, which are cleared from circulation faster than whole
      immunoglobulins. Rebound botulism after antitoxin administration is not
      previously documented but occurred in our patient 10 days after HBAT
      administration.

PMID- 21896701
TI  - Time to address stimulant abuse on our campuses.

PMID- 21896703
TI  - Varenicline: quantifying the risk.

PMID- 21896704
TI  - Varenicline: quantifying the risk.

PMID- 21896705
TI  - Varenicline: quantifying the risk.

PMID- 21896706
TI  - Varenicline: quantifying the risk.

PMID- 21896708
TI  - Varenicline: quantifying the risk.

PMID- 21896709
TI  - Varenicline: cardiovascular safety.

PMID- 21896711
TI  - Delayed diagnosis of Kaposi's sarcoma in a HIV positive man with a high CD4 count
      and suppressed viral load.
AB  - A HIV positive man with a CD4 count of 777*10(6)/l and suppressed viral load on
      antiretroviral medication had a delayed diagnosis of Kaposi's sarcoma (KS)
      affecting his left leg. He was diabetic and on a controlled diet and had a
      previous deep vein thrombosis affecting the same leg. Factors that have been
      studied in HIV-related KS as well as classical KS, such as diabetes mellitus, not
      smoking and previous deep vein thrombosis, may have increased our patient's risk
      for the development of this disease. Clinicians should consider KS as a possible
      diagnosis even in patients with well-controlled HIV.

PMID- 21896712
TI  - Dyspnoea severity and pneumonia as predictors of in-hospital mortality and early
      readmission in acute exacerbations of COPD.
AB  - BACKGROUND: Rates of mortality and readmission are high in patients hospitalised
      with acute exacerbations of chronic obstructive pulmonary disease (AECOPD). In
      this population, the prognostic value of the Medical Research Council Dyspnoea
      Scale (MRCD) is uncertain, and an extended MRCD (eMRCD) scale has been proposed
      to improve its utility. Coexistent pneumonia is common and, although the CURB-65
      prediction tool is used, its discriminatory value has not been reported. METHODS:
      Clinical and demographic data were collected on consecutive patients hospitalised
      with AECOPD. The relationship of stable-state dyspnoea severity to in-hospital
      mortality and 28-day readmission was assessed. The discriminatory value of CURB
      65, MRCD and eMRCD, in the prediction of in-hospital mortality, was assessed and
      compared. RESULTS: 920 patients were recruited. 10.4% died in-hospital and 19.1%
      of the 824 survivors were readmitted within 28 days of discharge. During their
      stable state prior to admission, 34.2% of patients were too breathless to leave
      the house. Mortality was significantly higher in pneumonic than in non-pneumonic
      exacerbations (20.1% vs 5.8%, p<0.001). eMRCD was a significantly better
      discriminator than either CURB-65 or the traditional MRCD scale for predicting in
      hospital mortality, and was a stronger prognostic tool than CURB-65 in the
      subgroup of patients with pneumonic AECOPD. CONCLUSIONS: The severity of dyspnoea
      in the stable state predicts important clinical outcomes in patients hospitalised
      with AECOPD. The eMRCD scale identifies a subgroup of patients at a particularly
      high risk of in-hospital mortality and is a better predictor of mortality risk
      than CURB-65 in exacerbations complicated by pneumonia.

PMID- 21896713
TI  - Ca2+/calmodulin-dependent kinase (CaMK) signaling via CaMKI and AMP-activated
      protein kinase contributes to the regulation of WIPI-1 at the onset of autophagy.
AB  - Autophagy is initiated by multimembrane vesicle (autophagosome) formation upon
      mammalian target of rapamycin inhibition and phosphatidylinositol 3-phosphate
      [PtdIns(3)P] generation. Upstream of microtubule-associated protein 1 light chain
      3 (LC3), WD-repeat proteins interacting with phosphoinositides (WIPI proteins)
      specifically bind PtdIns(3)P at forming autophagosomal membranes and become
      membrane-bound proteins of generated autophagosomes. Here, we applied automated
      high-throughput WIPI-1 puncta analysis, paralleled with LC3 lipidation assays, to
      investigate Ca(2+)-mediated autophagy modulation. We imposed cellular stress by
      starvation or administration of etoposide (0.5-50 MUM), sorafenib (1-40 MUM),
      staurosporine (20-500 nM), or thapsigargin (20-500 nM) (1, 2, or 3 h) and
      measured the formation of WIPI-1 positive autophagosomal membranes. Automated
      analysis of up to 5000 individual cells/treatment demonstrated that Ca(2+)
      chelation by BAPTA-AM (10 and 30 MUM) counteracted starvation or pharmacological
      compound-induced WIPI-1 puncta formation and LC3 lipidation. Application of
      selective Ca(2+)/calmodulin-dependent kinase kinase (CaMKK) alpha/beta and
      calmodulin-dependent kinase (CaMK) I/II/IV inhibitors 7-oxo-7H-benzimidazo[2,1
      a]benz[de]isoquinoline-3-carboxylic acid acetate (STO-609; 10-30 MUg/ml) and 2-(N
      [2-hydroxyethyl])-N-(4-methoxybenzenesulfonyl)amino-N-(4-chlorocinnamyl)-N
      methylamine (KN-93; 1-10 MUM), respectively, significantly reduced starvation
      induced autophagosomal membrane formation, suggesting that Ca(2+) mobilization
      upon autophagy induction involves CaMKI/IV. By small interefering RNA (siRNA)
      mediated down-regulation of CaMKI or CaMKIV, we demonstrate that CaMKI
      contributes to stimulation of WIPI-1. In line, WIPI-1 positive autophagosomal
      membranes were formed in AMP-activated protein kinase (AMPK) alpha(1)/alpha(2)
      deficient mouse embryonic fibroblasts upon nutrient starvation, whereas basal
      autophagy was prominently reduced. However, transient down-regulation of AMPK by
      siRNA resulted in an increased basal level of both WIPI-1 puncta and LC3
      lipidation, and nutrient-starvation induced autophagy was sensitive to STO-609/KN
      93. Our data provide evidence that pharmacological compound-modulated and
      starvation-induced autophagy involves Ca(2+)-dependent signaling, including CaMKI
      independent of AMPKalpha(1)/alpha(2). Our data also suggest that
      AMPKalpha(1)/alpha(2) might differentially contribute to the regulation of WIPI-1
      at the onset of autophagy.

PMID- 21896714
TI  - Direct measurements of DNA-mediated colloidal interactions and their quantitative
      modeling.
AB  - DNA bridging can be used to induce specific attractions between small particles,
      providing a highly versatile approach to creating unique particle-based materials
      having a variety of periodic structures. Surprisingly, given the fact that the
      thermodynamics of DNA strands in solution are completely understood, existing
      models for DNA-induced particle interactions are typically in error by more than
      an order of magnitude in strength and a factor of two in their temperature
      dependence. This discrepancy has stymied efforts to design the complex
      temperature, sequence and time-dependent interactions needed for the most
      interesting applications, such as materials having highly complex or
      multicomponent microstructures or the ability to reconfigure or self-replicate.
      Here we report high-spatial resolution measurements of DNA-induced interactions
      between pairs of polystyrene microspheres at binding strengths comparable to
      those used in self-assembly experiments, up to 6 k(B)T. We also describe a
      conceptually straightforward and numerically tractable model that quantitatively
      captures the separation dependence and temperature-dependent strength of these
      DNA-induced interactions, without empirical corrections. This model was equally
      successful when describing the more complex and practically relevant case of
      grafted DNA brushes with self-interactions that compete with interparticle bridge
      formation. Together, our findings motivate a nanomaterial design approach where
      unique functional structures can be found computationally and then reliably
      realized in experiment.

PMID- 21896715
TI  - Sensing cooperativity in ATP hydrolysis for single multisubunit enzymes in
      solution.
AB  - In order to operate in a coordinated fashion, multisubunit enzymes use
      cooperative interactions intrinsic to their enzymatic cycle, but this process
      remains poorly understood. Accordingly, ATP number distributions in various
      hydrolyzed states have been obtained for single copies of the mammalian double
      ring multisubunit chaperonin TRiC/CCT in free solution using the emission from
      chaperonin-bound fluorescent nucleotides and closed-loop feedback trapping
      provided by an Anti-Brownian ELectrokinetic trap. Observations of the 16-subunit
      complexes as ADP molecules are dissociating shows a peak in the bound ADP number
      distribution at 8 ADP, whose height falls over time with little shift in the
      position of the peak, indicating a highly cooperative ADP release process which
      would be difficult to observe by ensemble-averaged methods. When AlFx is added to
      produce ATP hydrolysis transition state mimics (ADP.AlFx) locked to the complex,
      the peak at 8 nucleotides dominates for all but the lowest incubation
      concentrations. Although ensemble averages of the single-molecule data show
      agreement with standard cooperativity models, surprisingly, the observed number
      distributions depart from standard models, illustrating the value of these single
      molecule observations in constraining the mechanism of cooperativity. While a
      complete alternative microscopic model cannot be defined at present, the addition
      of subunit-occupancy-dependent cooperativity in hydrolysis yields distributions
      consistent with the data.

PMID- 21896716
TI  - A unifying approach for food webs, phylogeny, social networks, and statistics.
AB  - A food web consists of nodes, each consisting of one or more species. The role of
      each node as predator or prey determines the trophic relations that weave the
      web. Much effort in trophic food web research is given to understand the
      connectivity structure, or the nature and degree of dependence among nodes.
      Social network analysis (SNA) techniques--quantitative methods commonly used in
      the social sciences to understand network relational structure--have been used
      for this purpose, although postanalysis effort or biological theory is still
      required to determine what natural factors contribute to the feeding behavior.
      Thus, a conventional SNA alone provides limited insight into trophic structure.
      Here we show that by using novel statistical modeling methodologies to express
      network links as the random response of within- and internode characteristics
      (predictors), we gain a much deeper understanding of food web structure and its
      contributing factors through a unified statistical SNA. We do so for eight
      empirical food webs: Phylogeny is shown to have nontrivial influence on trophic
      relations in many webs, and for each web trophic clustering based on feeding
      activity and on feeding preference can differ substantially. These and other
      conclusions about network features are purely empirical, based entirely on
      observed network attributes while accounting for biological information built
      directly into the model. Thus, statistical SNA techniques, through statistical
      inference for feeding activity and preference, provide an alternative perspective
      of trophic clustering to yield comprehensive insight into food web structure.

PMID- 21896717
TI  - Structural basis for the broad specificity to host-cell ligands by the pathogenic
      fungus Candida albicans.
AB  - Candida albicans is the most prevalent fungal pathogen in humans and a major
      source of life-threatening nosocomial infections. The Als (agglutinin-like
      sequence) glycoproteins are an important virulence factor for this fungus and
      have been associated with binding of host-cell surface proteins and small
      peptides of random sequence, the formation of biofilms and amyloid fibers. High
      resolution structures of N-terminal Als adhesins (NT-Als; up to 314 amino acids)
      show that ligand recognition relies on a motif capable of binding flexible C
      termini of peptides in extended conformation. Central to this mechanism is an
      invariant lysine that recognizes the C-terminal carboxylate of ligands at the end
      of a deep-binding cavity. In addition to several protein-peptide interactions, a
      network of water molecules runs parallel to one side of the ligand and
      contributes to the recognition of diverse peptide sequences. These data establish
      NT-Als adhesins as a separate family of peptide-binding proteins and an
      unexpected adhesion system for primary, widespread protein-protein interactions
      at the Candida/host-cell interface.

PMID- 21896718
TI  - General hydrophobic interaction potential for surfactant/lipid bilayers from
      direct force measurements between light-modulated bilayers.
AB  - We establish and quantify correlations among the molecular structures,
      interaction forces, and physical processes associated with light-responsive self
      assembled surfactant monolayers or bilayers at interfaces. Using the surface
      forces apparatus (SFA), the interaction forces between adsorbed monolayers and
      bilayers of an azobenzene-functionalized surfactant can be drastically and
      controllably altered by light-induced conversion of trans and cis molecular
      conformations. These reversible conformation changes affect significantly the
      shape of the molecules, especially in the hydrophobic region, which induces
      dramatic transformations of molecular packing in self-assembled structures,
      causing corresponding modulation of electrostatic double layer, steric hydration,
      and hydrophobic interactions. For bilayers, the isomerization from trans to cis
      exposes more hydrophobic groups, making the cis bilayers more hydrophobic, which
      lowers the activation energy barrier for (hemi)fusion. A quantitative and general
      model is derived for the interaction potential of charged bilayers that includes
      the electrostatic double-layer force of the Derjaguin-Landau-Verwey-Overbeek
      theory, attractive hydrophobic interactions, and repulsive steric-hydration
      forces. The model quantitatively accounts for the elastic strains, deformations,
      long-range forces, energy maxima, adhesion minima, as well as the instability
      (when it exists) as two bilayers breakthrough and (hemi)fuse. These results have
      several important implications, including quantitative and qualitative
      understanding of the hydrophobic interaction, which is furthermore shown to be a
      nonadditive interaction.

PMID- 21896720
TI  - 3D lithography by rapid curing of the liquid instabilities at nanoscale.
AB  - In liquids realm, surface tension and capillarity are the key forces driving the
      formation of the shapes pervading the nature. The steady dew drops appearing on
      plant leaves and spider webs result from the minimization of the overall surface
      energy [Zheng Y, et al. (2010) Nature 463:640-643]. Thanks to the surface
      tension, the interfaces of such spontaneous structures exhibit extremely good
      spherical shape and consequently worthy optical quality. Also nanofluidic
      instabilities generate a variety of fascinating liquid silhouettes, but they are
      however intrinsically short-lived. Here we show that such unsteady liquid
      structures, shaped in polymeric liquids by an electrohydrodynamic pressure, can
      be rapidly cured by appropriate thermal treatments. The fabrication of many solid
      microstructures exploitable in photonics is demonstrated, thus leading to a new
      concept in 3D lithography. The applicability of specific structures as optical
      tweezers and as novel remotely excitable quantum dots-embedded microresonators is
      presented.

PMID- 21896719
TI  - Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide
      synthesis.
AB  - Nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) are synthesized within cardiac
      myocytes and play key roles in modulating cardiovascular signaling. Cardiac
      myocytes contain both the endothelial (eNOS) and neuronal (nNOS) NO synthases,
      but the differential roles of these NOS isoforms and the interplay of reactive
      oxygen species and reactive nitrogen species in cardiac signaling pathways are
      poorly understood. Using a recently developed NO chemical sensor [Cu(2)(FL2E)] to
      study adult cardiac myocytes from wild-type, eNOS(null), and nNOS(null) mice, we
      discovered that physiological concentrations of H(2)O(2) activate eNOS but not
      nNOS. H(2)O(2)-stimulated eNOS activation depends on phosphorylation of both the
      AMP-activated protein kinase and kinase Akt, and leads to the robust
      phosphorylation of eNOS. Cardiac myocytes isolated from mice infected with
      lentivirus expressing the recently developed H(2)O(2) biosensor HyPer2 show
      marked H(2)O(2) synthesis when stimulated by angiotensin II, but not following
      beta-adrenergic receptor activation. We discovered that the angiotensin-II
      promoted increase in cardiac myocyte contractility is dependent on H(2)O(2),
      whereas beta-adrenergic contractile responses occur independently of H(2)O(2)
      signaling. These studies establish differential roles for H(2)O(2) in control of
      cardiac contractility and receptor-dependent NOS activation in the heart, and
      they identify new points for modulation of NO signaling responses by oxidant
      stress.

PMID- 21896721
TI  - Function of leukemogenic mixed lineage leukemia 1 (MLL) fusion proteins through
      distinct partner protein complexes.
AB  - A number of acute leukemias arise from fusion of the mixed lineage leukemia 1
      protein (MLL) N terminus to a variety of fusion partners that have been reported
      to reside in one or more poorly defined complexes linked to transcription
      elongation through interactions with the histone H3-K79 methyltransferase DOT1
      and positive transcription elongation factor b (P-TEFb). Here we first identify
      natural complexes (purified through fusion partners AF9, AF4, and ELL) with
      overlapping components, different elongation activities, and different cofactor
      associations that suggest dynamic interactions. Then, through reconstitution of
      defined, functionally active minimal complexes, we identify stable subcomplexes
      that, through newly defined protein-protein interactions, form distinct higher
      order complexes. These definitive analyses show, for example, that (i) through
      direct interactions with AF9 and cyclinT1, family members AF4 and AFF4
      independently mediate association of P-TEFb with AF9, (ii) P-TEFb, through direct
      interactions, provides the link for association of ELL and ELL-associated factors
      1 and 2 (EAF1 and EAF2) with AF4, and (iii) in the absence of other factors, DOT1
      forms a stable complex with AF9 and does not interact with AF9*AF4*P-TEFb
      complexes. Finally, we show the importance of defined higher order complex
      formation in MLL-AF9-mediated transcriptional up-regulation and cell
      immortalization potential in vivo. Thus, our study provides direct mechanistic
      insight into the role of fusion partners in MLL fusion-mediated leukemogenesis.

PMID- 21896722
TI  - Misfolded human tRNA isodecoder binds and neutralizes a 3' UTR-embedded Alu
      element.
AB  - Several classes of small noncoding RNAs are key players in cellular metabolism
      including mRNA decoding, RNA processing, and mRNA stability. Here we show that a
      tRNA(Asp) isodecoder, corresponding to a human tRNA-derived sequence, binds to an
      embedded Alu RNA element contained in the 3' UTR of the human aspartyl-tRNA
      synthetase mRNA. This interaction between two well-known classes of RNA
      molecules, tRNA and Alu RNA, is driven by an unexpected structural motif and
      induces a global rearrangement of the 3' UTR. Besides, this 3' UTR contains two
      functional polyadenylation signals. We propose a model where the tRNA/Alu
      interaction would modulate the accessibility of the two alternative
      polyadenylation sites and regulate the stability of the mRNA. This unique
      regulation mechanism would link gene expression to RNA polymerase III
      transcription and may have implications in a primate-specific signal pathway.

PMID- 21896723
TI  - Kinetically inhibited order in a diamond-lattice antiferromagnet.
AB  - Frustrated magnetic systems exhibit highly degenerate ground states and strong
      fluctuations, often leading to new physics. An intriguing example of current
      interest is the antiferromagnet on a diamond lattice, realized physically in A
      site spinel materials. This is a prototypical system in three dimensions where
      frustration arises from competing interactions rather than purely geometric
      constraints, and theory suggests the possibility of unusual magnetic order at low
      temperature. Here, we present a comprehensive single-crystal neutron scattering
      study of CoAl(2)O(4), a highly frustrated A-site spinel. We observe strong
      diffuse scattering that peaks at wavevectors associated with Neel ordering. Below
      the temperature T(*) = 6.5 K, there is a dramatic change in the elastic
      scattering lineshape accompanied by the emergence of well-defined spin-wave
      excitations. T(*) had previously been associated with the onset of glassy
      behavior. Our new results suggest instead that T(*) signifies a first-order phase
      transition, but with true long-range order inhibited by the kinetic freezing of
      domain walls. This scenario might be expected to occur widely in frustrated
      systems containing first-order phase transitions and is a natural explanation for
      existing reports of anomalous glassy behavior in other materials.

PMID- 21896724
TI  - In vivo protein-interaction mapping of a mitochondrial translocator protein Tom22
      at work.
AB  - Mitochondrial protein import requires cooperation of the machineries called
      translocators in the outer and inner mitochondrial membranes. Here we analyze the
      interactions of Tom22, a multifunctional subunit of the outer membrane
      translocator TOM40 complex, with other translocator subunits such as Tom20,
      Tom40, and Tim50 and with substrate precursor proteins at a spatial resolution of
      the amino acid residue by in vivo and in organello site-specific photocross
      linking. Changes in cross-linking patterns caused by excess substrate precursor
      proteins or presequence peptides indicate how the cytosolic receptor domain of
      Tom22 accepts substrate proteins and how the intermembrane space domain of Tom22
      transfers them to Tim50 of the inner-membrane translocator.

PMID- 21896725
TI  - In situ engineering of the lymph node microenvironment via intranodal injection
      of adjuvant-releasing polymer particles.
AB  - Recent studies have demonstrated a simple, potentially universal strategy to
      enhance vaccine potency, via intralymph node (i.LN) injection. To date,
      intranodal immunization studies have focused on the delivery of unadjuvanted
      vaccines (e.g., naked DNA, peptide, or protein). We hypothesized that combining
      i.LN vaccination with controlled release biomaterials permitting sustained dosing
      of molecular adjuvants to the local tissue microenvironment would further enhance
      this promising vaccination strategy. To test this idea, we encapsulated the Toll
      like receptor-3 ligand poly(inosinic:cytidylic acid) (polyIC) in biodegradable
      poly(lactide-co-glycolide) microparticles (MPs) designed to remain extracellular
      and release polyIC in the LN over several days. Intranodal injection of MPs
      increased persistence of polyIC in LNs compared to the same dose of soluble
      polyIC or polyIC formulated in nanoparticles, leading to increased accumulation
      of Toll-like receptor agonist in LN-resident antigen presenting cells and more
      enduring dendritic cell activation. Intralymph node injection of ovalbumin mixed
      with polyIC-releasing MPs enhanced the humoral response and expanded ovalbumin
      specific T cells to frequencies as high as 18% among all CD8(+) cells following a
      single injection (8.2-fold greater than the same vaccine given i.m.), a response
      that could not be matched by antigen mixed with polyIC-loaded nanoparticles or a
      10-fold greater dose of soluble polyIC. Thus, i.LN immunization with slow release
      formulated adjuvants may be a broadly applicable strategy to enhance therapeutic
      or prophylactic vaccines.

PMID- 21896726
TI  - Transcription factor TFIIF is not required for initiation by RNA polymerase II,
      but it is essential to stabilize transcription factor TFIIB in early elongation
      complexes.
AB  - Transcription factors TFIIB and TFIIF are both required for RNA polymerase II
      preinitiation complex (PIC) assembly, but their roles at and downstream of
      initiation are not clear. We now show that TFIIF phosphorylated by casein kinase
      2 remains competent to support PIC assembly but is not stably retained in the
      PIC. PICs completely lacking TFIIF are not defective in initiation or subsequent
      promoter clearance, demonstrating that TFIIF is not required for initiation or
      clearance. Lack of TFIIF in the PIC reduces transcription levels at some
      promoters, coincident with reduced retention of TFIIB. TFIIB is normally
      associated with the early elongation complex and is only destabilized at +12 to
      +13. However, if TFIIF is not retained in the PIC, TFIIB can be lost immediately
      after initiation. TFIIF therefore has an important role in stabilizing TFIIB
      within the PIC and after transcription initiates.

PMID- 21896727
TI  - Opening the periplasmic cavity in lactose permease is the limiting step for sugar
      binding.
AB  - The lactose permease (LacY) catalyzes galactoside/H(+) symport via an alternating
      access mechanism in which sugar- and H(+)-binding sites in the middle of the
      molecule are alternatively exposed to either side of the membrane by opening and
      closing of inward- and outward-facing cavities. The crystal structures of wild
      type LacY, as well as accessibility data for the protein in the membrane, provide
      strong support for a conformation with a tightly closed periplasmic side and an
      open cytoplasmic side (an inward-facing conformation). In this study, rates of
      substrate binding were measured by stopped-flow with purified LacY either in
      detergent or in reconstituted proteoliposomes. Binding rates are compared with
      rates of sugar-induced opening of the periplasmic pathway obtained by using a
      recently developed method based on unquenching of Trp fluorescence. A linear
      dependence of galactoside-binding rates on sugar concentration is observed in
      detergent, whereas reconstituted LacY binds substrate at a slower rate that is
      independent of sugar concentration. Rates of opening of the periplasmic cavity
      with LacY in detergent are independent of substrate concentration and are
      essentially the same for different galactosidic sugars. The findings demonstrate
      clearly that reconstituted LacY is oriented physiologically with a closed
      periplasmic side that limits access of sugar to the binding site. Moreover,
      opening of the periplasmic cavity is the limiting factor for sugar binding with
      reconstituted LacY and may be the limiting step in the overall transport
      reaction.

PMID- 21896728
TI  - Genetic evidence for a protective role of the peritrophic matrix against
      intestinal bacterial infection in Drosophila melanogaster.
AB  - The peritrophic matrix (PM) forms a layer composed of chitin and glycoproteins
      that lines the insect intestinal lumen. This physical barrier plays a role
      analogous to that of mucous secretions of the vertebrate digestive tract and is
      thought to protect the midgut epithelium from abrasive food particles and
      microbes. Almost nothing is known about PM functions in Drosophila, and its
      function as an immune barrier has never been addressed by a genetic approach.
      Here we show that the Drosocrystallin (Dcy) protein, a putative component of the
      eye lens of Drosophila, contributes to adult PM formation. A loss-of-function
      mutation in the dcy gene results in a reduction of PM width and an increase of
      its permeability. Upon bacterial ingestion a higher level of expression of
      antibacterial peptides was observed in dcy mutants, pointing to an influence of
      this matrix on bacteria sensing by the Imd immune pathway. Moreover, dcy
      deficient flies show an increased susceptibility to oral infections with the
      entomopathogenic bacteria Pseudomonas entomophila and Serratia marcescens. Dcy
      mutant flies also succumb faster than wild type upon ingestion of a P.
      entomophila toxic extract. We show that this lethality is due in part to an
      increased deleterious action of Monalysin, a pore-forming toxin produced by P.
      entomophila. Collectively, our analysis of the dcy immune phenotype indicates
      that the PM plays an important role in Drosophila host defense against enteric
      pathogens, preventing the damaging action of pore-forming toxins on intestinal
      cells.

PMID- 21896730
TI  - Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca2+
      release channel by NADPH oxidase 4.
AB  - Physiological sensing of O(2) tension (partial O(2) pressure, pO(2)) plays an
      important role in some mammalian cellular systems, but striated muscle generally
      is not considered to be among them. Here we describe a molecular mechanism in
      skeletal muscle that acutely couples changes in pO(2) to altered calcium release
      through the ryanodine receptor-Ca(2+)-release channel (RyR1). Reactive oxygen
      species are generated in proportion to pO(2) by NADPH oxidase 4 (Nox4) in the
      sarcoplasmic reticulum, and the consequent oxidation of a small set of RyR1
      cysteine thiols results in increased RyR1 activity and Ca(2+) release in isolated
      sarcoplasmic reticulum and in cultured myofibers and enhanced contractility of
      intact muscle. Thus, Nox4 is an O(2) sensor in skeletal muscle, and O(2)-coupled
      hydrogen peroxide production by Nox4 governs the redox state of regulatory RyR1
      thiols and thereby governs muscle performance. These findings reveal a molecular
      mechanism for O(2)-based signaling by an NADPH oxidase and demonstrate a
      physiological role for oxidative modification of RyR1.

PMID- 21896731
TI  - Amino acid substitution in NPC1 that abolishes cholesterol binding reproduces
      phenotype of complete NPC1 deficiency in mice.
AB  - Substitution mutations in adjacent amino acids of the N-terminal domain of NPC1,
      a lysosomal membrane protein, abolish its cholesterol binding activity and impair
      its ability to export cholesterol from lysosomes of cultured cells lacking npc1
      [Kwon HJ, et al. (2009) Cell 137:1213-1224]. Here, we show that the same two
      mutations (proline-202 and phenylalanine-203, both changed to alanine) reproduce
      the phenotype of complete NPC1 deficiency when knocked into the mouse npc1 gene
      by homologous recombination. Homozygous npc1(pf/pf) mice exhibited
      neurodegeneration beginning at day 49 and died at a median age of 84 d, as
      previously reported for mice that lack npc1. Liver and other organs of the
      npc1(pf/pf) mice accumulated excess cholesterol in lysosomes. In liver, mRNAs
      encoding several lysosomal proteins were elevated, including NPC1 and NPC2 and
      several digestive enzymes (acid lipase, beta-glucuronidase, and cathepsins B and
      D). Weekly treatment with hydroxypropyl-beta-cyclodextrin (HPCD) beginning at 7
      wk reduced hepatic cholesterol accumulation and diminished the lysosomal mRNAs.
      We conclude that the cholesterol binding site in the N-terminal domain of NPC1 is
      essential for cholesterol export from lysosomes in living animals as it is in
      cultured cells. The HPCD-mediated reduction of excess lysosomal enzymes may
      contribute to the ability of this drug to delay the progression of NPC disease in
      mice.

PMID- 21896733
TI  - Fossil evidence of avian crops from the Early Cretaceous of China.
AB  - The crop is characteristic of seed-eating birds today, yet little is known about
      its early history despite remarkable discoveries of many Mesozoic seed-eating
      birds in the past decade. Here we report the discovery of some early fossil
      evidence for the presence of a crop in birds. Two Early Cretaceous birds, the
      basal ornithurine Hongshanornis and a basal avian Sapeornis, demonstrate that an
      essentially modern avian digestive system formed early in avian evolution. The
      discovery of a crop in two phylogenetically remote lineages of Early Cretaceous
      birds and its absence in most intervening forms indicates that it was
      independently acquired as a specialized seed-eating adaptation. Finally, the
      reduction or loss of teeth in the forms showing seed-filled crops suggests that
      granivory was possibly one of the factors that resulted in the reduction of teeth
      in early birds.

PMID- 21896732
TI  - Interplay between spontaneous and induced brain activity during human non-rapid
      eye movement sleep.
AB  - Humans are less responsive to the surrounding environment during sleep. However,
      the extent to which the human brain responds to external stimuli during sleep is
      uncertain. We used simultaneous EEG and functional MRI to characterize brain
      responses to tones during wakefulness and non-rapid eye movement (NREM) sleep.
      Sounds during wakefulness elicited responses in the thalamus and primary auditory
      cortex. These responses persisted in NREM sleep, except throughout spindles,
      during which they became less consistent. When sounds induced a K complex,
      activity in the auditory cortex was enhanced and responses in distant frontal
      areas were elicited, similar to the stereotypical pattern associated with slow
      oscillations. These data show that sound processing during NREM sleep is
      constrained by fundamental brain oscillatory modes (slow oscillations and
      spindles), which result in a complex interplay between spontaneous and induced
      brain activity. The distortion of sensory information at the thalamic level,
      especially during spindles, functionally isolates the cortex from the environment
      and might provide unique conditions favorable for off-line memory processing.

PMID- 21896734
TI  - Neurofibromatosis-1 regulates mTOR-mediated astrocyte growth and glioma formation
      in a TSC/Rheb-independent manner.
AB  - Converging evidence from the analysis of human brain tumors and genetically
      engineered mice has revealed that the mammalian target of rapamycin (mTOR)
      pathway is a central regulator of glial and glioma cell growth. In this regard,
      mutational inactivation of neurofibromatosis-1 (NF1), tuberous sclerosis complex
      (TSC), and PTEN genes is associated with glioma formation, such that
      pharmacologic inhibition of mTOR signaling results in attenuated tumor growth.
      This shared dependence on mTOR suggests that PTEN and NF1 (neurofibromin) glial
      growth regulation requires TSC/Rheb (Ras homolog enriched in brain) control of
      mTOR function. In this report, we use a combination of genetic silencing in vitro
      and conditional mouse transgenesis approaches in vivo to demonstrate that
      neurofibromin regulates astrocyte cell growth and glioma formation in a TSC/Rheb
      independent fashion. First, we show that Nf1 or Pten inactivation, but not Tsc1
      loss or Rheb overexpression, increases astrocyte cell growth in vitro. Second,
      Nf1-deficient increased mTOR signaling and astrocyte hyperproliferation is
      unaffected by Rheb shRNA silencing. Third, conditional Tsc1 inactivation or Rheb
      overexpression in glial progenitors of Nf1(+/-) mice does not lead to glioma
      formation. Collectively, these findings establish TSC/Rheb-independent mechanisms
      for mTOR-dependent glial cell growth control and gliomagenesis relevant to the
      design of therapies for individuals with glioma.

PMID- 21896735
TI  - Genetic evidence for archaic admixture in Africa.
AB  - A long-debated question concerns the fate of archaic forms of the genus Homo: did
      they go extinct without interbreeding with anatomically modern humans, or are
      their genes present in contemporary populations? This question is typically
      focused on the genetic contribution of archaic forms outside of Africa. Here we
      use DNA sequence data gathered from 61 noncoding autosomal regions in a sample of
      three sub-Saharan African populations (Mandenka, Biaka, and San) to test models
      of African archaic admixture. We use two complementary approximate-likelihood
      approaches and a model of human evolution that involves recent population
      structure, with and without gene flow from an archaic population. Extensive
      simulation results reject the null model of no admixture and allow us to infer
      that contemporary African populations contain a small proportion of genetic
      material (~ 2%) that introgressed ~ 35 kya from an archaic population that split
      from the ancestors of anatomically modern humans ~ 700 kya. Three candidate
      regions showing deep haplotype divergence, unusual patterns of linkage
      disequilibrium, and small basal clade size are identified and the distributions
      of introgressive haplotypes surveyed in a sample of populations from across sub
      Saharan Africa. One candidate locus with an unusual segment of DNA that extends
      for >31 kb on chromosome 4 seems to have introgressed into modern Africans from a
      now-extinct taxon that may have lived in central Africa. Taken together our
      results suggest that polymorphisms present in extant populations introgressed via
      relatively recent interbreeding with hominin forms that diverged from the
      ancestors of modern humans in the Lower-Middle Pleistocene.

PMID- 21896736
TI  - Developmental basis of sexually dimorphic digit ratios.
AB  - Males and females generally have different finger proportions. In males, digit 2
      is shorter than digit 4, but in females digit 2 is the same length or longer than
      digit 4. The second- to fourth-digit (2D:4D) ratio correlates with numerous
      sexually dimorphic behavioral and physiological conditions. Although
      correlational studies suggest that digit ratios reflect prenatal exposure to
      androgen, the developmental mechanism underlying sexually dimorphic digit
      development remains unknown. Here we report that the 2D:4D ratio in mice is
      controlled by the balance of androgen to estrogen signaling during a narrow
      window of digit development. Androgen receptor (AR) and estrogen receptor alpha
      (ER-alpha) activity is higher in digit 4 than in digit 2. Inactivation of AR
      decreases growth of digit 4, which causes a higher 2D:4D ratio, whereas
      inactivation of ER-alpha increases growth of digit 4, which leads to a lower
      2D:4D ratio. We also show that addition of androgen has the same effect as
      inactivation of ER and that addition of estrogen mimics the reduction of AR.
      Androgen and estrogen differentially regulate the network of genes that controls
      chondrocyte proliferation, leading to differential growth of digit 4 in males and
      females. These studies identify previously undescribed molecular dimorphisms
      between male and female limb buds and provide experimental evidence that the
      digit ratio is a lifelong signature of prenatal hormonal exposure. Our results
      also suggest that the 2D:4D ratio can serve as an indicator of disrupted
      endocrine signaling during early development, which may aid in the identification
      of fetal origins of adult diseases.

PMID- 21896737
TI  - Neural-specific elongation of 3' UTRs during Drosophila development.
AB  - The 3' termini of eukaryotic mRNAs influence transcript stability, translation
      efficiency, and subcellular localization. Here we report that a subset of
      developmental regulatory genes, enriched in critical RNA-processing factors,
      exhibits synchronous lengthening of their 3' UTRs during embryogenesis. The
      resulting UTRs are up to 20-fold longer than those found on typical Drosophila
      mRNAs. The large mRNAs emerge shortly after the onset of zygotic transcription,
      with several of these genes acquiring additional, phased UTR extensions later in
      embryogenesis. We show that these extended 3' UTR sequences are selectively
      expressed in neural tissues and contain putative recognition motifs for the
      translational repressor, Pumilio, which also exhibits the 3' lengthening
      phenomenon documented in this study. These findings suggest a previously unknown
      mode of posttranscriptional regulation that may contribute to the complexity of
      neurogenesis or neural function.

PMID- 21896738
TI  - Modulatory profiling identifies mechanisms of small molecule-induced cell death.
AB  - Cell death is a complex process that plays a vital role in development,
      homeostasis, and disease. Our understanding of and ability to control cell death
      is impeded by an incomplete characterization of the full range of cell death
      processes that occur in mammalian systems, especially in response to exogenous
      perturbations. We present here a general approach to address this problem, which
      we call modulatory profiling. Modulatory profiles are composed of the changes in
      potency and efficacy of lethal compounds produced by a second cell death
      modulating agent in human cell lines. We show that compounds with the same
      characterized mechanism of action have similar modulatory profiles. Furthermore,
      clustering of modulatory profiles revealed relationships not evident when
      clustering lethal compounds based on gene expression profiles alone. Finally,
      modulatory profiling of compounds correctly predicted three previously
      uncharacterized compounds to be microtubule-destabilizing agents, classified
      numerous compounds that act nonspecifically, and identified compounds that cause
      cell death through a mechanism that is morphologically and biochemically distinct
      from previously established ones.

PMID- 21896740
TI  - Interdomain movements in metabotropic glutamate receptor activation.
AB  - Many cell surface receptors are multimeric proteins, composed of several
      structural domains, some involved in ligand recognition, whereas others are
      responsible for signal transduction. In most cases, the mechanism of how ligand
      interaction in the extracellular domains leads to the activation of effector
      domains remains largely unknown. Here we examined how the extracellular ligand
      binding to the venus flytrap (VFT) domains of the dimeric metabotropic glutamate
      receptors activate the seven transmembrane (7TM) domains responsible for G
      protein activation. These two domains are interconnected by a cysteine-rich
      domain (CRD). We show that any of the four disulfide bridges of the CRD are
      required for the allosteric coupling between the VFT and the 7TM domains. More
      importantly, we show that a specific association of the two CRDs corresponds to
      the active state of the receptor. Indeed, a specific crosslinking of the CRDs
      with intersubunit disulfide bridges leads to fully constitutively active
      receptors, no longer activated by agonists nor by allosteric modulators. These
      data demonstrate that intersubunit movement at the level of the CRDs represents a
      key step in metabotropic glutamate receptor activation.

PMID- 21896739
TI  - Second-generation high-throughput forward genetic screen in mice to isolate
      subtle behavioral mutants.
AB  - Forward genetic screens have been highly successful in revealing roles of genes
      and pathways in complex biological events. Traditionally these screens have
      focused on isolating mutants with the greatest phenotypic deviance, with the
      hopes of discovering genes that are central to the biological event being
      investigated. Behavioral screens in mice typically use simple activity-based
      assays as endophenotypes for more complex emotional states of the animal. They
      generally set the selection threshold for a putative mutant at 3 SDs (z score of
      3) from the average behavior of normal animals to minimize false-positive
      results. Behavioral screens using a high threshold for detection have generally
      had limited success, with high false-positive rates and subtle phenotypic
      differences that have made mapping and cloning difficult. In addition, targeted
      reverse genetic approaches have shown that when genes central to behaviors such
      as open field behavior, psychostimulant response, and learning and memory tasks
      are mutated, they produce subtle phenotypes that differ from wild-type animals by
      1 to 2 SDs (z scores of 1 to 2). We have conducted a second-generation (G2)
      dominant N-ethyl-N-nitrosourea (ENU) screen especially designed to detect subtle
      behavioral mutants for open field activity and psychostimulant response
      behaviors. We successfully detect mutant lines with only 1 to 2 SD shifts in mean
      response compared with wild-type control animals and present a robust statistical
      and methodological framework for conducting such forward genetic screens. Using
      this methodology we have screened 229 ENU mutant lines and have identified 15
      heritable mutant lines. We conclude that for screens in mice that use activity
      based endophenotypic measurements for complex behavioral states, this G2
      screening approach yields better results.

PMID- 21896741
TI  - Finding the ciliary beating pattern with optimal efficiency.
AB  - We introduce a measure for energetic efficiency of biological cilia acting
      individually or collectively and numerically determine the optimal beating
      patterns according to this criterion. Maximizing the efficiency of a single
      cilium leads to curly, often symmetric, and somewhat counterintuitive patterns.
      However, when looking at a densely ciliated surface, the optimal patterns become
      remarkably similar to what is observed in microorganisms like Paramecium. The
      optimal beating pattern then consists of a fast effective stroke and a slow
      sweeping recovery stroke. Metachronal coordination is essential for efficient
      pumping and the highest efficiency is achieved with antiplectic waves. Efficiency
      also increases with an increasing density of cilia up to the point where crowding
      becomes a problem. We finally relate the pumping efficiency of cilia to the
      swimming efficiency of a spherical microorganism and show that the experimentally
      estimated efficiency of Paramecium is surprisingly close to the theoretically
      possible optimum.

PMID- 21896742
TI  - Recovery of stereopsis through perceptual learning in human adults with abnormal
      binocular vision.
AB  - Stereopsis, the perception of depth based on the disparity of the images
      projected to the retinas of the two eyes, is an important process in our three
      dimensional world; however, 3-5% of the population is stereoblind or has
      seriously impaired stereovision. Here we provide evidence for the recovery of
      stereopsis through perceptual learning, the repetitive practice of a demanding
      visual task, in human adults long deprived of normal binocular vision. We used a
      training paradigm that combines monocular cues that were correlated perfectly
      with the disparity cues. Following perceptual learning (thousands of trials) with
      stereoscopic gratings, five adults who initially were stereoblind or
      stereoanomalous showed substantial recovery of stereopsis, both on psychophysical
      tests with stimuli that contained no monocular cues and on clinical testing. They
      reported that depth "popped out" in daily life, and enjoyed 3D movies for the
      first time. After training, stereo tests with dynamic random-dot stereograms and
      band-pass noise revealed the properties of the recovered stereopsis: It has
      reduced resolution and precision, although it is based on perceiving depth by
      detecting binocular disparity. We conclude that some human adults deprived of
      normal binocular vision can recover stereopsis at least partially.

PMID- 21896744
TI  - Drosophila P elements preferentially transpose to replication origins.
AB  - The P transposable element recently invaded wild Drosophila melanogaster strains
      worldwide. A single introduced copy can multiply and spread throughout the fly
      genome in just a few generations, even though its cut-and-paste transposition
      mechanism does not inherently increase copy number. P element insertions
      preferentially target the promoters of a subset of genes, but why these sites are
      hotspots remains unknown. We show that P elements selectively target sites that
      in tissue-culture cells bind origin recognition complex proteins and function as
      replication origins. The association of origin recognition complex-binding sites
      with selected promoters and their absence near clustered differentiation genes
      may dictate P element site specificity. Inserting at unfired replication origins
      during S phase may allow P elements to be both repaired and reduplicated, thereby
      increasing element copy number. The advantage transposons gain by moving from
      replicated to unreplicated genomic regions may contribute to the association of
      heterochromatin with late-replicating genomic regions.

PMID- 21896743
TI  - Crosstalk between the urokinase-type plasminogen activator receptor and EGF
      receptor variant III supports survival and growth of glioblastoma cells.
AB  - A truncated and constitutively active form of the EGF receptor, variant III
      (EGFRvIII), is a major determinant of tumor growth and progression in
      glioblastoma multiforme (GBM). Extensive bidirectional crosstalk occurs in the
      cell-signaling pathways downstream of the EGFR and the urokinase-type plasminogen
      activator receptor (uPAR); however, crosstalk between EGFRvIII and uPAR has not
      been examined. Here, we show that uPAR does not regulate ERK activation in
      EGFRvIII-expressing GBM cells; however, in GBM cells isolated from four separate
      xenografts in which EGFRvIII expression was down-regulated in vivo, uPAR assumed
      a major role in sustaining ERK activation. Phosphorylation of Tyr-845 in the
      EGFR, which is mediated by Src family kinases, depended on uPAR in EGFRvIII
      expressing GBM cells. Activation of the mitogenic and prosurvival transcription
      factor, STAT5b, downstream of EGFRvIII, also required uPAR. The EGFR-selective
      tyrosine kinase inhibitors, erlotinib and gefitinib, blocked not only EGFRvIII
      signaling to ERK but also uPAR-dependent STAT5b activation. uPAR gene silencing
      in EGFRvIII-expressing GBM cells and in cells from tumors that escaped dependency
      on EGFRvIII decreased cell survival and proliferation. Xenografts of EGFRvIII
      expressing cancer cell lines and a human GBM, which was propagated as a
      xenograft, were robustly immunopositive for uPAR and phospho-Tyr-845 by
      immunohistochemistry. A human GBM in which the EGFR gene was amplified without
      truncation was immunonegative for both uPAR and phospho-Tyr-845. These studies
      identify distinct cell-signaling activities for uPAR in GBM cells that express
      EGFRvIII and in cells released from dormancy when EGFRvIII is neutralized. uPAR
      and its crosstalk pathways with EGFRvIII emerge as logical targets for
      therapeutics development in GBM.

PMID- 21896745
TI  - Heparan sulfate binding by natural eastern equine encephalitis viruses promotes
      neurovirulence.
AB  - The Alphavirus genus of the family Togaviridae contains mosquito-vectored viruses
      that primarily cause either arthritogenic disease or acute encephalitis. North
      American eastern equine encephalitis virus (NA-EEEV) is uniquely neurovirulent
      among encephalitic alphaviruses, causing mortality in a majority of symptomatic
      cases and neurological sequelae in many survivors. Unlike many alphaviruses, NA
      EEEV infection of mice yields limited signs of febrile illness typically
      associated with lymphoid tissue replication. Rather, signs of brain infection,
      including seizures, are prominent. Use of heparan sulfate (HS) as an attachment
      receptor increases the neurovirulence of cell culture-adapted strains of Sindbis
      virus, an arthritogenic alphavirus. However, this receptor is not known to be
      used by naturally circulating alphaviruses. We demonstrate that wild-type NA-EEEV
      strain FL91-4679 uses HS as an attachment receptor and that the amino acid
      sequence of its E2 attachment protein is identical to those of natural isolates
      sequenced by RT-PCR amplification of field samples. This finding unequivocally
      confirms the use of HS receptors by naturally circulating NA-EEEV strains.
      Inactivation of the major HS binding domain in NA-EEEV E2 demonstrated that the
      HS binding increased brain replication and neurologic disease but reduced
      lymphoid tissue replication, febrile illness signs, and cytokine/chemokine
      induction in mice. We propose that HS binding by natural NA-EEEV strains alters
      tropism in vivo to antagonize/evade immune responses, and the extreme
      neurovirulence of wild-type NA-EEEV may be a consequence. Therefore,
      reinvestigation of HS binding by this and other arboviruses is warranted.

PMID- 21896746
TI  - Cultivation of an obligate acidophilic ammonia oxidizer from a nitrifying acid
      soil.
AB  - Nitrification is a fundamental component of the global nitrogen cycle and leads
      to significant fertilizer loss and atmospheric and groundwater pollution.
      Nitrification rates in acidic soils (pH < 5.5), which comprise 30% of the world's
      soils, equal or exceed those of neutral soils. Paradoxically, autotrophic ammonia
      oxidizing bacteria and archaea, which perform the first stage in nitrification,
      demonstrate little or no growth in suspended liquid culture below pH 6.5, at
      which ammonia availability is reduced by ionization. Here we report the discovery
      and cultivation of a chemolithotrophic, obligately acidophilic thaumarchaeal
      ammonia oxidizer, "Candidatus Nitrosotalea devanaterra," from an acidic
      agricultural soil. Phylogenetic analysis places the organism within a previously
      uncultivated thaumarchaeal lineage that has been observed in acidic soils. Growth
      of the organism is optimal in the pH range 4 to 5 and is restricted to the pH
      range 4 to 5.5, unlike all previously cultivated ammonia oxidizers. Growth of
      this organism and associated ammonia oxidation and autotrophy also occur during
      nitrification in soil at pH 4.5. The discovery of Nitrosotalea devanaterra
      provides a previously unsuspected explanation for high rates of nitrification in
      acidic soils, and confirms the vital role that thaumarchaea play in terrestrial
      nitrogen cycling. Growth at extremely low ammonia concentration (0.18 nM) also
      challenges accepted views on ammonia uptake and metabolism and indicates novel
      mechanisms for ammonia oxidation at low pH.

PMID- 21896747
TI  - A special pair of phytohormones controls excitability, slow closure, and external
      stomach formation in the Venus flytrap.
AB  - Venus flytrap's leaves can catch an insect in a fraction of a second. Since the
      time of Charles Darwin, scientists have struggled to understand the sensory
      biology and biomechanics of this plant, Dionaea muscipula. Here we show that
      insect-capture of Dionaea traps is modulated by the phytohormone abscisic acid
      (ABA) and jasmonates. Water-stressed Dionaea, as well as those exposed to the
      drought-stress hormone ABA, are less sensitive to mechanical stimulation. In
      contrast, application of 12-oxo-phytodienoic acid (OPDA), a precursor of the
      phytohormone jasmonic acid (JA), the methyl ester of JA (Me-JA), and coronatine
      (COR), the molecular mimic of the isoleucine conjugate of JA (JA-Ile), triggers
      secretion of digestive enzymes without any preceding mechanical stimulus. Such
      secretion is accompanied by slow trap closure. Under physiological conditions,
      insect-capture is associated with Ca(2+) signaling and a rise in OPDA,
      Apparently, jasmonates bypass hapto-electric processes associated with trap
      closure. However, ABA does not affect OPDA-dependent gland activity. Therefore,
      signals for trap movement and secretion seem to involve separate pathways.
      Jasmonates are systemically active because application to a single trap induces
      secretion and slow closure not only in the given trap but also in all others.
      Furthermore, formerly touch-insensitive trap sectors are converted into
      mechanosensitive ones. These findings demonstrate that prey-catching Dionaea
      combines plant-specific signaling pathways, involving OPDA and ABA with a rapidly
      acting trigger, which uses ion channels, action potentials, and Ca(2+) signals.

PMID- 21896748
TI  - Alternative splicing of a single transcription factor drives selfish reproductive
      behavior in honeybee workers (Apis mellifera).
AB  - In eusocial insects the production of daughters is generally restricted to mated
      queens, and unmated workers are functionally sterile. The evolution of this
      worker sterility has been plausibly explained by kin selection theory [Hamilton W
      (1964) J Theor Biol 7:1-52], and many traits have evolved to prevent conflict
      over reproduction among the females in an insect colony. In honeybees (Apis
      mellifera), worker reproduction is regulated by the queen, brood pheromones, and
      worker policing. However, workers of the Cape honeybee, Apis mellifera capensis,
      can evade this control and establish themselves as social parasites by activating
      their ovaries, parthenogenetically producing diploid female offspring (thelytoky)
      and producing queen-like amounts of queen pheromones. All these traits have been
      shown to be strongly influenced by a single locus on chromosome 13 [Lattorff HMG,
      et al. (2007) Biol Lett 3:292-295]. We screened this region for candidate genes
      and found that alternative splicing of a gene homologous to the gemini
      transcription factor of Drosophila controls worker sterility. Knocking out the
      critical exon in a series of RNAi experiments resulted in rapid worker ovary
      activation-one of the traits characteristic of the social parasites. This genetic
      switch may be controlled by a short intronic splice enhancer motif of nine
      nucleotides attached to the alternative splice site. The lack of this motif in
      parasitic Cape honeybee clones suggests that the removal of nine nucleotides from
      the altruistic worker genome may be sufficient to turn a honeybee from an
      altruistic worker into a parasite.

PMID- 21896749
TI  - Circadian transcriptional regulation by the posttranslational oscillator without
      de novo clock gene expression in Synechococcus.
AB  - Circadian rhythms are a fundamental property of most organisms, from
      cyanobacteria to humans. In the unicellular obligately photoautotrophic
      cyanobacterium Synechococcus elongatus PCC 7942, essentially all promoter
      activities are controlled by the KaiABC-based clock under continuous light
      conditions. When Synechococcus cells are transferred from the light to continuous
      dark (DD) conditions, the expression of most genes, including the clock genes
      kaiA and kaiBC, is rapidly down-regulated, whereas the KaiC phosphorylation cycle
      persists. Therefore, we speculated that the posttranslational oscillator might
      not drive the transcriptional circadian output without de novo expression of the
      kai genes. Here we show that the cyanobacterial clock regulates the
      transcriptional output even in the dark. The expression of a subset of genes in
      the genomes of cells grown in the dark was dramatically affected by kaiABC
      nullification, and the magnitude of dark induction was dependent on the time at
      which the cells were transferred from the light to the dark. Moreover, under DD
      conditions, the expression of some dark-induced gene transcripts exhibited
      temperature-compensated damped oscillations, which were nullified in kaiABC-null
      strains and were affected by a kaiC period mutation. These results indicate that
      the Kai protein-based posttranslational oscillator can drive the circadian
      transcriptional output even without the de novo expression of the clock genes.

PMID- 21896750
TI  - Extracellular reduction of uranium via Geobacter conductive pili as a protective
      cellular mechanism.
AB  - The in situ stimulation of Fe(III) oxide reduction by Geobacter bacteria leads to
      the concomitant precipitation of hexavalent uranium [U(VI)] from groundwater.
      Despite its promise for the bioremediation of uranium contaminants, the
      biological mechanism behind this reaction remains elusive. Because Fe(III) oxide
      reduction requires the expression of Geobacter's conductive pili, we evaluated
      their contribution to uranium reduction in Geobacter sulfurreducens grown under
      pili-inducing or noninducing conditions. A pilin-deficient mutant and a
      genetically complemented strain with reduced outer membrane c-cytochrome content
      were used as controls. Pili expression significantly enhanced the rate and extent
      of uranium immobilization per cell and prevented periplasmic mineralization. As a
      result, pili expression also preserved the vital respiratory activities of the
      cell envelope and the cell's viability. Uranium preferentially precipitated along
      the pili and, to a lesser extent, on outer membrane redox-active foci. In
      contrast, the pilus-defective strains had different degrees of periplasmic
      mineralization matching well with their outer membrane c-cytochrome content. X
      ray absorption spectroscopy analyses demonstrated the extracellular reduction of
      U(VI) by the pili to mononuclear tetravalent uranium U(IV) complexed by carbon
      containing ligands, consistent with a biological reduction. In contrast, the
      U(IV) in the pilin-deficient mutant cells also required an additional phosphorous
      ligand, in agreement with the predominantly periplasmic mineralization of uranium
      observed in this strain. These findings demonstrate a previously unrecognized
      role for Geobacter conductive pili in the extracellular reduction of uranium, and
      highlight its essential function as a catalytic and protective cellular mechanism
      that is of interest for the bioremediation of uranium-contaminated groundwater.

PMID- 21896751
TI  - Inhibition of influenza virus replication via small molecules that induce the
      formation of higher-order nucleoprotein oligomers.
AB  - Influenza nucleoprotein (NP) plays multiple roles in the virus life cycle,
      including an essential function in viral replication as an integral component of
      the ribonucleoprotein complex, associating with viral RNA and polymerase within
      the viral core. The multifunctional nature of NP makes it an attractive target
      for antiviral intervention, and inhibitors targeting this protein have recently
      been reported. In a parallel effort, we discovered a structurally similar series
      of influenza replication inhibitors and show that they interfere with NP
      dependent processes via formation of higher-order NP oligomers. Support for this
      unique mechanism is provided by site-directed mutagenesis studies, biophysical
      characterization of the oligomeric ligand:NP complex, and an X-ray cocrystal
      structure of an NP dimer of trimers (or hexamer) comprising three NP_A:NP_B
      dimeric subunits. Each NP_A:NP_B dimeric subunit contains two ligands that bridge
      two composite, protein-spanning binding sites in an antiparallel orientation to
      form a stable quaternary complex. Optimization of the initial screening hit
      produced an analog that protects mice from influenza-induced weight loss and
      mortality by reducing viral titers to undetectable levels throughout the course
      of treatment.

PMID- 21896752
TI  - Oxytocin receptor gene (OXTR) is related to psychological resources.
AB  - Psychological resources--optimism, mastery, and self-esteem--buffer the
      deleterious effects of stress and are predictors of neurophysiological and
      psychological health-related outcomes. These resources have been shown to be
      highly heritable, yet the genetic basis for this heritability remains unknown.
      Here, we report a link between the oxytocin receptor (OXTR) SNP rs53576 and
      psychological resources, such that carriers of the "A" allele have lower levels
      of optimism, mastery, and self-esteem, relative to G/G homozygotes. OXTR was also
      associated with depressive symptomatology. Mediation analysis indicates that the
      effects of OXTR on depressive symptoms may be largely mediated by the influence
      of OXTR on psychological resources.

PMID- 21896753
TI  - MicroRNA-149*, a p53-responsive microRNA, functions as an oncogenic regulator in
      human melanoma.
AB  - The tumor suppressor p53 is activated in response to cellular stress to prevent
      malignant transformation by activation of the DNA repair machinery to preserve
      the cell, or by induction of apoptosis to eliminate the cell should the damage
      prove irrevocable. The gene encoding p53 frequently undergoes inactivating
      mutations in many human cancers, but WT p53 is often expressed at high levels in
      melanoma, which, as judged from the malignant nature of the disease, fails to act
      as an effective tumor suppressor. Here we show that p53 directly up-regulates
      microRNA-149* (miR-149*) that in turn targets glycogen synthase kinase-3alpha,
      resulting in increased expression of Mcl-1 and resistance to apoptosis in
      melanoma cells. Although deficiency in miR-149* undermined survival of melanoma
      cells and inhibited melanoma growth in a mouse xenograft model, elevated
      expression of miR-149* was found in fresh human metastatic melanoma isolates,
      which was associated with decreased glycogen synthase kinase-3alpha and increased
      Mcl-1. These results reveal a p53-dependent, miR-149*-mediated pathway that
      contributes to survival of melanoma cells, provides a rational explanation for
      the ineffectiveness of p53 to suppress melanoma, and identifies the expression of
      miR-149* as a mechanism involved in the increased expression of Mcl-1 in melanoma
      cells.

PMID- 21896754
TI  - Pattern of trauma determines the threshold for epileptic activity in a model of
      cortical deafferentation.
AB  - Epileptic activity often occurs in the cortex after a latent period after head
      trauma; this delay has been attributed to the destabilizing influence of
      homeostatic synaptic scaling and changes in intrinsic properties. However, the
      impact of the spatial organization of cortical trauma on epileptogenesis is
      poorly understood. We addressed this question by analyzing the dynamics of a
      large-scale biophysically realistic cortical network model subjected to different
      patterns of trauma. Our results suggest that the spatial pattern of trauma can
      greatly affect the propensity for developing posttraumatic epileptic activity.
      For the same fraction of lesioned neurons, spatially compact trauma resulted in
      stronger posttraumatic elevation of paroxysmal activity than spatially diffuse
      trauma. In the case of very severe trauma, diffuse distribution of a small number
      of surviving intact neurons alleviated posttraumatic epileptogenesis. We suggest
      that clinical evaluation of the severity of brain trauma should take into account
      the spatial pattern of the injured cortex.

PMID- 21896755
TI  - Arbovirus high fidelity variant loses fitness in mosquitoes and mice.
AB  - The error rate of RNA-dependent RNA polymerases (RdRp) affects the mutation
      frequency in a population of viral RNAs. Using chikungunya virus (CHIKV), we
      describe a unique arbovirus fidelity variant with a single C483Y amino acid
      change in the nsP4 RdRp that increases replication fidelity and generates
      populations with reduced genetic diversity. In mosquitoes, high fidelity CHIKV
      presents lower infection and dissemination titers than wild type. In newborn
      mice, high fidelity CHIKV produces truncated viremias and lower organ titers.
      These results indicate that increased replication fidelity and reduced genetic
      diversity negatively impact arbovirus fitness in invertebrate and vertebrate
      hosts.

PMID- 21896756
TI  - Targeted killing of a mammalian cell based upon its specialized metabolic state.
AB  - Mouse ES cells use a mitochondrial threonine dehydrogenase (TDH) enzyme to
      catabolize threonine into glycine and acetyl-CoA. Measurements of mRNA abundance
      have given evidence that ES cells express upwards of 1,000-fold higher levels of
      TDH mRNA than any of seven other mouse tissues tested. When cell culture medium
      is deprived of threonine, ES cells rapidly discontinue DNA synthesis, arrest cell
      division, and eventually die. Such studies led to the conclusion that mouse ES
      cells exist in a threonine-dependent metabolic state. Proceeding with the
      assumption that the active TDH enzyme should be essential for the growth and
      viability of mouse ES cells, we performed a drug screen in search of specific
      inhibitors of the purified TDH enzyme. Such efforts led to the discovery of a
      class of quinazolinecarboxamide (Qc) compounds that inhibit the ability of the
      TDH enzyme to catabolize threonine into glycine and acetyl-CoA. Administration of
      Qc inhibitors of TDH to mouse ES cells impeded cell growth and resulted in the
      induction of autophagy. By contrast, the same chemicals failed to affect the
      growth of HeLa cells at concentrations 300-fold higher than that required to kill
      mouse ES cells. It was likewise observed that the Qc class of TDH inhibitors
      failed to affect the growth or viability of ES cell-derived embryoid body cells
      known to have extinguished TDH expression. These studies demonstrate how it is
      possible to kill a specific mammalian cell type on the basis of its specialized
      metabolic state.

PMID- 21896758
TI  - Sneak peak at galactocerebrosidase, Krabbe disease's lysosomal hydrolase.

PMID- 21896757
TI  - Prostaglandin E2 release from astrocytes triggers gonadotropin-releasing hormone
      (GnRH) neuron firing via EP2 receptor activation.
AB  - Astrocytes in the hypothalamus release prostaglandin E(2) (PGE(2)) in response to
      cell-cell signaling initiated by neurons and glial cells. Upon release, PGE(2)
      stimulates the secretion of gonadotropin-releasing hormone (GnRH), the
      neuropeptide that controls reproduction, from hypothalamic neuroendocrine
      neurons. Whether this effect on GnRH secretion is accompanied by changes in the
      firing behavior of these neurons is unknown. Using patch-clamp recording we
      demonstrate that PGE(2) exerts a dose-dependent postsynaptic excitatory effect on
      GnRH neurons. These effects are mimicked by an EP2 receptor agonist and
      attenuated by protein kinase A (PKA) inhibitors. The acute blockade of
      prostaglandin synthesis by indomethacin (INDO) or the selective inhibition of
      astrocyte metabolism by fluoroacetate (FA) suppresses the spontaneous firing
      activity of GnRH neurons in brain slices. Similarly, GnRH neuronal activity is
      reduced in mice with impaired astrocytic PGE(2) release due to defective erbB
      signaling in astrocytes. These results indicate that astrocyte-to-neuron
      communication in the hypothalamus is essential for the activity of GnRH neurons
      and suggest that PGE(2) acts as a gliotransmitter within the GnRH neurosecretory
      system.

PMID- 21896759
TI  - Restraint of angiogenesis by zinc finger transcription factor CTCF-dependent
      chromatin insulation.
AB  - Angiogenesis is meticulously controlled by a fine balance between positive and
      negative regulatory activities. Vascular endothelial growth factor (VEGF) is a
      predominant angiogenic factor and its dosage is precisely regulated during normal
      vascular formation. In cancer, VEGF is commonly overproduced, resulting in
      abnormal neovascularization. VEGF is induced in response to various stimuli
      including hypoxia; however, very little is known about the mechanisms that
      confine its induction to ensure proper angiogenesis. Chromatin insulation is a
      key transcription mechanism that prevents promiscuous gene activation by
      interfering with the action of enhancers. Here we show that the chromatin
      insulator-binding factor CTCF binds to the proximal promoter of VEGF. Consistent
      with the enhancer-blocking mode of chromatin insulators, CTCF has little effect
      on basal expression of VEGF but specifically affects its activation by enhancers.
      CTCF knockdown cells are sensitized for induction of VEGF and exhibit elevated
      proangiogenic potential. Cancer-derived CTCF missense mutants are mostly
      defective in blocking enhancers at the VEGF locus. Moreover, during mouse retinal
      development, depletion of CTCF causes excess angiogenesis. Therefore, CTCF
      mediated chromatin insulation acts as a crucial safeguard against hyperactivation
      of angiogenesis.

PMID- 21896760
TI  - Medial prefrontal cortex and striatum mediate the influence of social comparison
      on the decision process.
AB  - We compared private and social decision making to investigate the neural
      underpinnings of the effect of social comparison on risky choices. We measured
      brain activity using functional MRI while participants chose between two
      lotteries: in the private condition, they observed the outcome of the unchosen
      lottery, and in the social condition, the outcome of the lottery chosen by
      another person. The striatum, a reward-related brain structure, showed higher
      activity when participants won more than their counterpart (social gains)
      compared with winning in isolation and lower activity when they won less than
      their counterpart (social loss) compared with private loss. The medial prefrontal
      cortex, implicated in social reasoning, was more activated by social gains than
      all other events. Sensitivity to social gains influenced both brain activity and
      behavior during subsequent choices. Specifically, striatal activity associated
      with social gains predicted medial prefrontal cortex activity during social
      choices, and experienced social gains induced more risky and competitive behavior
      in later trials. These results show that interplay between reward and social
      reasoning networks mediates the influence of social comparison on the decision
      process.

PMID- 21896761
TI  - Reactibodies generated by kinetic selection couple chemical reactivity with
      favorable protein dynamics.
AB  - Igs offer a versatile template for combinatorial and rational design approaches
      to the de novo creation of catalytically active proteins. We have used a covalent
      capture selection strategy to identify biocatalysts from within a human
      semisynthetic antibody variable fragment library that uses a nucleophilic
      mechanism. Specific phosphonylation at a single tyrosine within the variable
      light-chain framework was confirmed in a recombinant IgG construct. High
      resolution crystallographic structures of unmodified and phosphonylated Fabs
      display a 15-A-deep two-chamber cavity at the interface of variable light (V(L))
      and variable heavy (V(H)) fragments having a nucleophilic tyrosine at the base of
      the site. The depth and structure of the pocket are atypical of antibodies in
      general but can be compared qualitatively with the catalytic site of
      cholinesterases. A structurally disordered heavy chain complementary determining
      region 3 loop, constituting a wall of the cleft, is stabilized after covalent
      modification by hydrogen bonding to the phosphonate tropinol moiety. These
      features and presteady state kinetics analysis indicate that an induced fit
      mechanism operates in this reaction. Mutations of residues located in this
      stabilized loop do not interfere with direct contacts to the organophosphate
      ligand but can interrogate second shell interactions, because the H3 loop has a
      conformation adjusted for binding. Kinetic and thermodynamic parameters along
      with computational docking support the active site model, including plasticity
      and simple catalytic components. Although relatively uncomplicated, this
      catalytic machinery displays both stereo- and chemical selectivity. The
      organophosphate pesticide paraoxon is hydrolyzed by covalent catalysis with rate
      limiting dephosphorylation. This reactibody is, therefore, a kinetically selected
      protein template that has enzyme-like catalytic attributes.

PMID- 21896762
TI  - Surface architecture of endospores of the Bacillus cereus/anthracis/thuringiensis
      family at the subnanometer scale.
AB  - Bacteria of the Bacillus cereus family form highly resistant spores, which in the
      case of the pathogen B. anthracis act as the agents of infection. The outermost
      layer, the exosporium, enveloping spores of the B. cereus family as well as a
      number of Clostridia, plays roles in spore adhesion, dissemination, targeting,
      and germination control. We have analyzed two naturally crystalline layers
      associated with the exosporium, one representing the "basal" layer to which the
      outermost spore layer ("hairy nap") is attached, and the other likely
      representing a subsurface ("parasporal") layer. We have used electron
      cryomicroscopy at a resolution of 0.8-0.6 nm and circular dichroism spectroscopic
      measurements to reveal a highly alpha-helical structure for both layers. The
      helices are assembled into 2D arrays of "cups" or "crowns." High-resolution
      atomic force microscopy of the outermost layer showed that the open ends of these
      cups face the external environment and the highly immunogenic collagen-like
      fibrils of the hairy nap (BclA) are attached to this surface. Based on our
      findings, we present a molecular model for the spore surface and propose how this
      surface can act as a semipermeable barrier and a matrix for binding of molecules
      involved in defense, germination control, and other interactions of the spore
      with the environment.

PMID- 21896763
TI  - MicroRNAs and phylogenomics resolve the relationships of Tardigrada and suggest
      that velvet worms are the sister group of Arthropoda.
AB  - Morphological data traditionally group Tardigrada (water bears), Onychophora
      (velvet worms), and Arthropoda (e.g., spiders, insects, and their allies) into a
      monophyletic group of invertebrates with walking appendages known as the
      Panarthropoda. However, molecular data generally do not support the inclusion of
      tardigrades within the Panarthropoda, but instead place them closer to Nematoda
      (roundworms). Here we present results from the analyses of two independent
      genomic datasets, expressed sequence tags (ESTs) and microRNAs (miRNAs), which
      congruently resolve the phylogenetic relationships of Tardigrada. Our EST
      analyses, based on 49,023 amino acid sites from 255 proteins, significantly
      support a monophyletic Panarthropoda including Tardigrada and suggest a sister
      group relationship between Arthropoda and Onychophora. Using careful experimental
      manipulations--comparisons of model fit, signal dissection, and taxonomic pruning
      -we show that support for a Tardigrada + Nematoda group derives from the
      phylogenetic artifact of long-branch attraction. Our small RNA libraries fully
      support our EST results; no miRNAs were found to link Tardigrada and Nematoda,
      whereas all panarthropods were found to share one unique miRNA (miR-276). In
      addition, Onychophora and Arthropoda were found to share a second miRNA (miR
      305). Our study confirms the monophyly of the legged ecdysozoans, shows that past
      support for a Tardigrada + Nematoda group was due to long-branch attraction, and
      suggests that the velvet worms are the sister group to the arthropods.

PMID- 21896764
TI  - A 5-methylcytosine DNA glycosylase/lyase demethylates the retrotransposon Tos17
      and promotes its transposition in rice.
AB  - DNA 5-methylcytosine (5-meC) is an important epigenetic mark for transcriptional
      gene silencing in many eukaryotes. In Arabidopsis, 5-meC DNA glycosylase/lyases
      actively remove 5-meC to counteract transcriptional gene silencing in a locus
      specific manner, and have been suggested to maintain the expression of
      transposons. However, it is unclear whether plant DNA demethylases can promote
      the transposition of transposons. Here we report the functional characterization
      of the DNA glycosylase/lyase DNG701 in rice. DNG701 encodes a large (1,812 amino
      acid residues) DNA glycosylase domain protein. Recombinant DNG701 protein showed
      5-meC DNA glycosylase and lyase activities in vitro. Knockout or knockdown of
      DNG701 in rice plants led to DNA hypermethylation and reduced expression of the
      retrotransposon Tos17. Tos17 showed less transposition in calli derived from
      dng701 knockout mutant seeds compared with that in wild-type calli.
      Overexpression of DNG701 in both rice calli and transgenic plants substantially
      reduced DNA methylation levels of Tos17 and enhanced its expression. The
      overexpression also led to more frequent transposition of Tos17 in calli. Our
      results demonstrate that rice DNG701 is a 5-meC DNA glycosylase/lyase responsible
      for the demethylation of Tos17 and this DNA demethylase plays a critical role in
      promoting Tos17 transposition in rice calli.

PMID- 21896765
TI  - Neural language networks at birth.
AB  - The ability to learn language is a human trait. In adults and children, brain
      imaging studies have shown that auditory language activates a bilateral
      frontotemporal network with a left hemispheric dominance. It is an open question
      whether these activations represent the complete neural basis for language
      present at birth. Here we demonstrate that in 2-d-old infants, the language
      related neural substrate is fully active in both hemispheres with a preponderance
      in the right auditory cortex. Functional and structural connectivities within
      this neural network, however, are immature, with strong connectivities only
      between the two hemispheres, contrasting with the adult pattern of prevalent
      intrahemispheric connectivities. Thus, although the brain responds to spoken
      language already at birth, thereby providing a strong biological basis to acquire
      language, progressive maturation of intrahemispheric functional connectivity is
      yet to be established with language exposure as the brain develops.

PMID- 21896766
TI  - Dopamine neurons learn to encode the long-term value of multiple future rewards.
AB  - Midbrain dopamine neurons signal reward value, their prediction error, and the
      salience of events. If they play a critical role in achieving specific distant
      goals, long-term future rewards should also be encoded as suggested in
      reinforcement learning theories. Here, we address this experimentally untested
      issue. We recorded 185 dopamine neurons in three monkeys that performed a
      multistep choice task in which they explored a reward target among alternatives
      and then exploited that knowledge to receive one or two additional rewards by
      choosing the same target in a set of subsequent trials. An analysis of
      anticipatory licking for reward water indicated that the monkeys did not
      anticipate an immediately expected reward in individual trials; rather, they
      anticipated the sum of immediate and multiple future rewards. In accordance with
      this behavioral observation, the dopamine responses to the start cues and
      reinforcer beeps reflected the expected values of the multiple future rewards and
      their errors, respectively. More specifically, when monkeys learned the multistep
      choice task over the course of several weeks, the responses of dopamine neurons
      encoded the sum of the immediate and expected multiple future rewards. The
      dopamine responses were quantitatively predicted by theoretical descriptions of
      the value function with time discounting in reinforcement learning. These
      findings demonstrate that dopamine neurons learn to encode the long-term value of
      multiple future rewards with distant rewards discounted.

PMID- 21896767
TI  - Expression of the Sendai (murine parainfluenza) virus C protein alleviates
      restriction of measles virus growth in mouse cells.
AB  - Measles virus (MV), a human pathogen, uses the signaling lymphocyte activation
      molecule (SLAM) or CD46 as an entry receptor. Although several transgenic mice
      expressing these receptors have been generated as small animal models for
      measles, these mice usually have to be made defective in IFN-alpha/beta signaling
      to facilitate MV replication. Similarly, when functional receptors are expressed
      by transfection, mouse cells do not allow MV growth as efficiently as primate
      cells. In this study, we demonstrate that MV efficiently grows in SLAM-expressing
      mouse cells in which the Sendai virus (SeV) C protein is transiently expressed.
      We developed a SLAM-expressing mouse cell line whose genome also encodes the SeV
      C protein downstream of the sequence flanked with loxP sequences. When this cell
      line was infected with the recombinant MV expressing the Cre recombinase, the SeV
      C protein was readily expressed. Importantly, the Cre recombinase-encoding MV
      grew in this cell line much more efficiently than it did in the parental cell.
      The minigenome assay demonstrated that the SeV C protein does not modulate MV RNA
      synthesis. Analyses using the mutant proteins with the defined functional defects
      revealed that the IFN-antagonist function, but not the budding-accelerating
      function, of the SeV C protein was critical for supporting efficient MV growth in
      mouse cells. Our results indicate that insufficient IFN antagonism can be an
      important determinant of the host range of viruses, and the system described here
      may be useful to overcome the species barrier of other human viruses.

PMID- 21896768
TI  - Expression of the metabotropic glutamate receptor 5 (mGluR5) induces melanoma in
      transgenic mice.
AB  - Glutamate is the major excitatory neurotransmitter in the mammalian CNS and
      mediates fast synaptic transmission upon activation of glutamate-gated ion
      channels. In addition, glutamate modulates a variety of other synaptic responses
      and intracellular signaling by activating metabotropic glutamate receptors
      (mGluRs), which are G protein-coupled receptors. The mGluRs are also expressed in
      nonneuronal tissues and are implicated in a variety of normal biological
      functions as well as diseases. To study mGluR-activated calcium signaling in
      neurons, we generated mGluR5 transgenic animals using a Thy1 promoter to drive
      expression in the forebrain, and one founder unexpectedly developed melanoma. To
      directly investigate the role of mGluR5 in melanoma formation, we generated
      mGluR5 transgenic lines under a melanocyte-specific promoter, tyrosinase-related
      protein 1. A majority of the founders showed a severe phenotype with early onset.
      Hyperpigmentation of the pinnae and tail could be detected as early as 3-5 d
      after birth for most of the mGluR5 transgene-positive mice. There was 100%
      penetrance in the progeny from the tyrosinase-related protein 1-mGluR5 lines
      generated from founders that developed melanoma. Expression of mGluR5 was
      detected in melanoma samples by RT-PCR, immunoblotting, and immunohistochemistry.
      We evaluated the expression of several cancer-related proteins in tumor samples
      and observed a dramatic increase in the phosphorylation of ERK, implicating ERK
      as a downstream effector of mGluR5 signaling in tumors. Our findings show that
      mGluR5-mediated glutamatergic signaling can trigger melanoma in vivo. The
      aggressive growth and severe phenotype make these mouse lines unique and a
      potentially powerful tool for therapeutic studies.

PMID- 21896769
TI  - AMP-activated protein kinase (AMPK) beta1beta2 muscle null mice reveal an
      essential role for AMPK in maintaining mitochondrial content and glucose uptake
      during exercise.
AB  - AMP-activated protein kinase (AMPK) beta1 or beta2 subunits are required for
      assembling of AMPK heterotrimers and are important for regulating enzyme activity
      and cellular localization. In skeletal muscle, alpha2beta2gamma3-containing
      heterotrimers predominate. However, compensatory up-regulation and redundancy of
      AMPK subunits in whole-body AMPK alpha2, beta2, and gamma3 null mice has made it
      difficult to determine the physiological importance of AMPK in regulating muscle
      metabolism, because these models have normal mitochondrial content, contraction
      stimulated glucose uptake, and insulin sensitivity. In the current study, we
      generated mice lacking both AMPK beta1 and beta2 isoforms in skeletal muscle
      (beta1beta2M-KO). beta1beta2M-KO mice are physically inactive and have a
      drastically impaired capacity for treadmill running that is associated with
      reductions in skeletal muscle mitochondrial content but not a fiber-type switch.
      Interestingly, young beta1beta2M-KO mice fed a control chow diet are not obese or
      insulin resistant but do have impaired contraction-stimulated glucose uptake.
      These data demonstrate an obligatory role for skeletal muscle AMPK in maintaining
      mitochondrial capacity and contraction-stimulated glucose uptake, findings that
      were not apparent in mice with single mutations or deletions in muscle alpha,
      beta, or gamma subunits.

PMID- 21896770
TI  - Carcinogenic bacterial pathogen Helicobacter pylori triggers DNA double-strand
      breaks and a DNA damage response in its host cells.
AB  - The bacterial pathogen Helicobacter pylori chronically infects the human gastric
      mucosa and is the leading risk factor for the development of gastric cancer. The
      molecular mechanisms of H. pylori-associated gastric carcinogenesis remain ill
      defined. In this study, we examined the possibility that H. pylori directly
      compromises the genomic integrity of its host cells. We provide evidence that the
      infection introduces DNA double-strand breaks (DSBs) in primary and transformed
      murine and human epithelial and mesenchymal cells. The induction of DSBs depends
      on the direct contact of live bacteria with mammalian cells. The infection
      associated DNA damage is evident upon separation of nuclear DNA by pulse field
      gel electrophoresis and by high-magnification microscopy of metaphase
      chromosomes. Bacterial adhesion (e.g., via blood group antigen-binding adhesin)
      is required to induce DSBs; in contrast, the H. pylori virulence factors
      vacuolating cytotoxin A, gamma-glutamyl transpeptidase, and the cytotoxin
      associated gene (Cag) pathogenicity island are dispensable for DSB induction. The
      DNA discontinuities trigger a damage-signaling and repair response involving the
      sequential ataxia telangiectasia mutated (ATM)-dependent recruitment of repair
      factors--p53-binding protein (53BP1) and mediator of DNA damage checkpoint
      protein 1 (MDC1)--and histone H2A variant X (H2AX) phosphorylation. Although most
      breaks are repaired efficiently upon termination of the infection, we observe
      that prolonged active infection leads to saturation of cellular repair
      capabilities. In summary, we conclude that DNA damage followed by potentially
      imprecise repair is consistent with the carcinogenic properties of H. pylori and
      with its mutagenic properties in vitro and in vivo and may contribute to the
      genetic instability and frequent chromosomal aberrations that are a hallmark of
      gastric cancer.

PMID- 21896771
TI  - Homeostatic plasticity drives tinnitus perception in an animal model.
AB  - Hearing loss often results in tinnitus and auditory cortical map changes, leading
      to the prevailing view that the phantom perception is associated with cortical
      reorganization. However, we show here that tinnitus is mediated by a cortical
      area lacking map reorganization. High-frequency hearing loss results in two
      distinct cortical regions: a sensory-deprived region characterized by a decrease
      in inhibitory synaptic transmission and a normal hearing region showing increases
      in inhibitory and excitatory transmission and map reorganization. Hearing
      lesioned animals displayed tinnitus with a pitch in the hearing loss range.
      Furthermore, drugs that enhance inhibition, but not those that reduce excitation,
      reversibly eliminated the tinnitus behavior. These results suggest that sensory
      deprivation-induced homeostatic down-regulation of inhibitory synapses may
      contribute to tinnitus perception. Enhancing sensory input through map
      reorganization may plausibly alleviate phantom sensation.

PMID- 21896773
TI  - Discovery of GAMA, a Plasmodium falciparum merozoite micronemal protein, as a
      novel blood-stage vaccine candidate antigen.
AB  - One of the solutions for reducing the global mortality and morbidity due to
      malaria is multivalent vaccines comprising antigens of several life cycle stages
      of the malarial parasite. Hence, there is a need for supplementing the current
      set of malaria vaccine candidate antigens. Here, we aimed to characterize
      glycosylphosphatidylinositol (GPI)-anchored micronemal antigen (GAMA) encoded by
      the PF08_0008 gene in Plasmodium falciparum. Antibodies were raised against
      recombinant GAMA synthesized by using a wheat germ cell-free system.
      Immunoelectron microscopy demonstrated for the first time that GAMA is a
      microneme protein of the merozoite. Erythrocyte binding assays revealed that GAMA
      possesses an erythrocyte binding epitope in the C-terminal region and it binds a
      nonsialylated protein receptor on human erythrocytes. Growth inhibition assays
      revealed that anti-GAMA antibodies can inhibit P. falciparum invasion in a dose
      dependent manner and GAMA plays a role in the sialic acid (SA)-independent
      invasion pathway. Anti-GAMA antibodies in combination with anti-erythrocyte
      binding antigen 175 exhibited a significantly higher level of invasion
      inhibition, supporting the rationale that targeting of both SA-dependent and SA
      independent ligands/pathways is better than targeting either of them alone. Human
      sera collected from areas of malaria endemicity in Mali and Thailand recognized
      GAMA. Since GAMA in P. falciparum is refractory to gene knockout attempts, it is
      essential to parasite invasion. Overall, our study indicates that GAMA is a novel
      blood-stage vaccine candidate antigen.

PMID- 21896772
TI  - PATRIC: the comprehensive bacterial bioinformatics resource with a focus on human
      pathogenic species.
AB  - Funded by the National Institute of Allergy and Infectious Diseases, the
      Pathosystems Resource Integration Center (PATRIC) is a genomics-centric
      relational database and bioinformatics resource designed to assist scientists in
      infectious-disease research. Specifically, PATRIC provides scientists with (i) a
      comprehensive bacterial genomics database, (ii) a plethora of associated data
      relevant to genomic analysis, and (iii) an extensive suite of computational tools
      and platforms for bioinformatics analysis. While the primary aim of PATRIC is to
      advance the knowledge underlying the biology of human pathogens, all publicly
      available genome-scale data for bacteria are compiled and continually updated,
      thereby enabling comparative analyses to reveal the basis for differences between
      infectious free-living and commensal species. Herein we summarize the major
      features available at PATRIC, dividing the resources into two major categories:
      (i) organisms, genomes, and comparative genomics and (ii) recurrent integration
      of community-derived associated data. Additionally, we present two experimental
      designs typical of bacterial genomics research and report on the execution of
      both projects using only PATRIC data and tools. These applications encompass a
      broad range of the data and analysis tools available, illustrating practical uses
      of PATRIC for the biologist. Finally, a summary of PATRIC's outreach activities,
      collaborative endeavors, and future research directions is provided.

PMID- 21896774
TI  - Role for the SRC family kinase Fyn in sphingolipid acquisition by chlamydiae.
AB  - The bacterial obligate intracellular pathogen Chlamydia trachomatis replicates
      within a membrane-bound vacuole termed the inclusion. From within this protective
      environment, chlamydiae usurp numerous functions of the host cell to promote
      chlamydial survival and replication. Here we utilized a small interfering RNA
      (siRNA)-based screening protocol designed to identify host proteins involved in
      the trafficking of sphingomyelin to the chlamydial inclusion. Twenty-six host
      proteins whose deficiency significantly decreased sphingomyelin trafficking to
      the inclusion and 16 proteins whose deficiency significantly increased
      sphingomyelin trafficking to the inclusion were identified. The reduced
      sphingomyelin trafficking caused by downregulation of the Src family tyrosine
      kinase Fyn was confirmed in more-detailed analyses. Fyn silencing did not alter
      sphingomyelin synthesis or trafficking in the absence of chlamydial infection but
      reduced the amount of sphingomyelin trafficked to the inclusion in infected
      cells, as determined by two independent quantitative assays. Additionally,
      inhibition of Src family kinases resulted in increased cellular retention of
      sphingomyelin and significantly decreased incorporation into elementary bodies of
      both C. trachomatis and Chlamydophila caviae.

PMID- 21896775
TI  - Comparative transcriptional study of the putative mannose donor biosynthesis
      genes in virulent Mycobacterium tuberculosis and attenuated Mycobacterium bovis
      BCG strains.
AB  - Mycobacterium tuberculosis contains mannosylated cell wall components which are
      important in macrophage recognition and response. The building block for the
      mannosyl constituents of these components is GDP-mannose, which is synthesized
      through a series of enzymes involved in the mannose donor biosynthesis pathway.
      Nothing is known about the expression levels of the genes encoding these enzymes
      during the course of infection. To generate transcriptional profiles for the
      mannose donor biosynthesis genes from virulent M. tuberculosis and attenuated
      Mycobacterium bovis BCG, bacteria were grown in broth culture and within human
      macrophages. Our results with broth-grown bacteria show that there are
      differences in expression of the selected genes between M. tuberculosis and BCG,
      with increased expression of manC in M. tuberculosis and manA in BCG during
      stationary-phase growth. Results for M. tuberculosis extracted from within
      macrophages show that whiB2 is highly expressed and manB and manC are moderately
      expressed during infection. Rv3256c, Rv3258c, and ppm1 have high expression
      levels early and decreased expression as the infection progresses. Results with
      BCG show that, as in M. tuberculosis, whiB2 is highly expressed throughout
      infection, whereas there is either low expression or little change in expression
      of the remaining genes studied. Overall, our results show that there is
      differential regulation of expression of several genes in the mannose donor
      biosynthesis pathway of M. tuberculosis and BCG grown in broth and within
      macrophages, raising the possibility that the level of mannose donors may vary
      during the course of infection and thereby impact the biosynthesis of mannose
      containing cell wall molecules.

PMID- 21896776
TI  - Role of interleukin-23 (IL-23) receptor signaling for IL-17 responses in human
      Lyme disease.
AB  - Interleukin-23 (IL-23) is known to play a crucial role in the development and
      maintenance of T helper 17 cells. It has been previously demonstrated that IL-17
      is involved in experimental Lyme arthritis, caused by Borrelia burgdorferi
      bacteria. However, the precise role of the IL-23 receptor (IL-23R) for the B.
      burgdorferi-induced IL-17 responses or human Lyme disease has not yet been
      elucidated. IL-23R single nucleotide polymorphism (SNP) rs11209026 was genotyped
      using the TaqMan assay. Functional studies were performed using peripheral blood
      mononuclear cells, and cytokines were measured using enzyme-linked immunosorbent
      assay (ELISA). Dose-dependent production of IL-23 and IL-17 by B. burgdorferi
      could be observed. Interestingly, when IL-23 bioactivity was inhibited by a
      specific antibody against IL-23p19, IL-17 production was significantly
      downregulated. In contrast, production of gamma interferon (IFN-gamma) was not
      affected after the blockade of IL-23 activity. Moreover, individuals bearing a
      single nucleotide polymorphism in the IL-23R gene (Arg381Gln) produced
      significantly less IL-17 after B. burgdorferi stimulation compared with that of
      the individuals bearing the wild type. Despite lower IL-17 production, the IL-23R
      gene polymorphism did not influence the development of chronic Lyme disease in a
      cohort of patients with Lyme disease. This study demonstrates that IL-23R
      signaling is needed for B. burgdorferi-induced IL-17 production in vitro and that
      an IL-23R gene SNP leads to impaired IL-17 production. However, the IL-23R gene
      polymorphism is not crucial for the pathogenesis of chronic Lyme.

PMID- 21896777
TI  - Outer membrane protein A of bovine and ovine isolates of Mannheimia haemolytica
      is surface exposed and contains host species-specific epitopes.
AB  - Mannheimia haemolytica is the etiological agent of pneumonic pasteurellosis of
      cattle and sheep; two different OmpA subclasses, OmpA1 and OmpA2, are associated
      with bovine and ovine isolates, respectively. These proteins differ at the distal
      ends of four external loops, are involved in adherence, and are likely to play
      important roles in host adaptation. M. haemolytica is surrounded by a
      polysaccharide capsule, and the degree of OmpA surface exposure is unknown. To
      investigate surface exposure and immune specificity of OmpA among bovine and
      ovine M. haemolytica isolates, recombinant proteins representing the
      transmembrane domain of OmpA from a bovine serotype A1 isolate (rOmpA1) and an
      ovine serotype A2 isolate (rOmpA2) were overexpressed, purified, and used to
      generate anti-rOmpA1 and anti-rOmpA2 antibodies, respectively. Immunogold
      electron microscopy and immunofluorescence techniques demonstrated that OmpA1 and
      OmpA2 are surface exposed, and are not masked by the polysaccharide capsule, in a
      selection of M. haemolytica isolates of various serotypes and grown under
      different growth conditions. To explore epitope specificity, anti-rOmpA1 and anti
      rOmpA2 antibodies were cross-absorbed with the heterologous isolate to remove
      cross-reacting antibodies. These cross-absorbed antibodies were highly specific
      and recognized only the OmpA protein of the homologous isolate in Western blot
      assays. A wider examination of the binding specificities of these antibodies for
      M. haemolytica isolates representing different OmpA subclasses revealed that
      cross-absorbed anti-rOmpA1 antibodies recognized OmpA1-type proteins but not
      OmpA2-type proteins; conversely, cross-absorbed anti-rOmpA2 antibodies recognized
      OmpA2-type proteins but not OmpA1-type proteins. Our results demonstrate that
      OmpA1 and OmpA2 are surface exposed and could potentially bind to different
      receptors in cattle and sheep.

PMID- 21896778
TI  - Induction of the alternative NF-kappaB pathway by lymphotoxin alphabeta
      (LTalphabeta) relies on internalization of LTbeta receptor.
AB  - Several tumor necrosis factor receptor (TNFR) family members activate both the
      classical and the alternative NF-kappaB pathways. However, how a single receptor
      engages these two distinct pathways is still poorly understood. Using lymphotoxin
      beta receptor (LTbetaR) as a prototype, we showed that activation of the
      alternative, but not the classical, NF-kappaB pathway relied on internalization
      of the receptor. Further molecular analyses revealed a specific cytosolic region
      of LTbetaR essential for its internalization, TRAF3 recruitment, and p100
      processing. Interestingly, we found that dynamin-dependent, but clathrin
      independent, internalization of LTbetaR appeared to be required for the
      activation of the alternative, but not the classical, NF-kappaB pathway. In vivo,
      ligand-induced internalization of LTbetaR in mesenteric lymph node stromal cells
      correlated with induction of alternative NF-kappaB target genes. Thus, our data
      shed light on LTbetaR cellular trafficking as a process required for specific
      biological functions of NF-kappaB.

PMID- 21896779
TI  - Feedback control of p53 translation by REDD1 and mTORC1 limits the p53-dependent
      DNA damage response.
AB  - Exquisite control of the level and activity of p53 are required in order to
      preserve cellular homeostasis following DNA damage. How this regulation is
      integrated with other key metabolic pathways in vivo is poorly understood. Here,
      we describe an endogenous feedback circuit for regulation of p53 through its
      transcriptional target gene, Redd1, a stress-induced inhibitor of TOR complex 1
      (TORC1) activity. Cells and tissues of Redd1(-/-) mice exhibit enhanced
      sensitivity to ionizing radiation and chemotherapy treatment, which we
      demonstrate is attributable to abnormally increased p53 protein level and
      activity in the absence of Redd1. We find that deregulation of p53 in this
      setting is not due to failed DNA repair or to increased p53 stabilization but,
      instead, to increased p53 translation. We show that Redd1 loss leads to elevated
      mammalian TORC1 (mTORC1) activity, which explains the increased p53 translation
      and protein levels. Together, these findings suggest that REDD1-mediated
      suppression of mTORC1 activity exerts feedback control on p53, thereby limiting
      the apoptotic response and contributing to cellular survival following DNA
      damage. This work therefore defines a role for REDD1 in the control of p53 in
      vivo, with potential therapeutic implications for cancer and for the variety of
      genetic diseases involving TOR pathway signaling components.

PMID- 21896780
TI  - Map2k4 functions as a tumor suppressor in lung adenocarcinoma and inhibits tumor
      cell invasion by decreasing peroxisome proliferator-activated receptor gamma2
      expression.
AB  - MAP2K4 encodes a dual-specificity kinase (mitogen-activated protein kinase kinase
      4, or MKK4) that is mutated in a variety of human malignancies, but the
      biochemical properties of the mutant kinases and their roles in tumorigenesis
      have not been fully elucidated. Here we showed that 8 out of 11 cancer-associated
      MAP2K4 mutations reduce MKK4 protein stability or impair its kinase activity. On
      the basis of findings from bioinformatic studies on human cancer cell lines with
      homozygous MAP2K4 loss, we posited that MKK4 functions as a tumor suppressor in
      lung adenocarcinomas that develop in mice owing to expression of mutant Kras and
      Tp53. Conditional Map2k4 inactivation in the bronchial epithelium of mice had no
      discernible effect alone but increased the multiplicity and accelerated the
      growth of incipient lung neoplasias induced by oncogenic Kras. MKK4 suppressed
      the invasion and metastasis of Kras-Tp53-mutant lung adenocarcinoma cells. MKK4
      deficiency increased peroxisomal proliferator-activated receptor gamma2
      (PPARgamma2) expression through noncanonical MKK4 substrates, and PPARgamma2
      enhanced tumor cell invasion. We conclude that Map2k4 functions as a tumor
      suppressor in lung adenocarcinoma and inhibits tumor cell invasion by decreasing
      PPARgamma2 levels.

PMID- 21896781
TI  - Evolution of nucleosome occupancy: conservation of global properties and
      divergence of gene-specific patterns.
AB  - To examine the role of nucleosome occupancy in the evolution of gene expression,
      we measured the genome-wide nucleosome profiles of four yeast species, three
      belonging to the Saccharomyces sensu stricto lineage and the more distantly
      related Candida glabrata. Nucleosomes and associated promoter elements at C.
      glabrata genes are typically shifted upstream by ~20 bp, compared to their
      orthologs from sensu stricto species. Nonetheless, all species display the same
      global organization features first described for Saccharomyces cerevisiae: a
      stereotypical nucleosome organization along genes and a division of promoters
      into those that contain or lack a pronounced nucleosome-depleted region (NDR),
      with the latter displaying a more dynamic pattern of gene expression. Despite
      this global similarity, however, nucleosome occupancy at specific genes diverged
      extensively between sensu stricto and C. glabrata orthologs (~50 million years).
      Orthologs with dynamic expression patterns tend to maintain their lack of NDR,
      but apart from that, sensu stricto and C. glabrata orthologs are nearly as
      similar in nucleosome occupancy patterns as nonorthologous genes. This extensive
      divergence in nucleosome occupancy contrasts with a conserved pattern of gene
      expression. Thus, while some evolutionary changes in nucleosome occupancy
      contribute to gene expression divergence, nucleosome occupancy often diverges
      extensively with apparently little impact on gene expression.

PMID- 21896782
TI  - Essential roles of ECAT15-2/Dppa2 in functional lung development.
AB  - Many transcription factors and DNA binding proteins play essential roles in the
      development of organs in which they are highly and/or specifically expressed.
      Embryonic stem cell (ESC)-associated transcript 15-1 (ECAT15-1) and ECAT15-2,
      also known as developmental pluripotency-associated 4 (Dppa4) and Dppa2,
      respectively, are enriched in mouse ESCs and preimplantation embryos, and their
      genes encode homologous proteins with a common DNA binding domain known as the
      SAP motif. Previously, ECAT15-1 was shown to be important in lung development,
      while it is dispensable in early development. In this study, we generated ECAT15
      2 single and ECAT15-1 ECAT15-2 double knockout (double KO) mice and found that
      almost all mutants, like ECAT15-1 mutants, died around birth with respiratory
      defects. Paradoxically, the expression of neither ECAT15-1 nor ECAT15-2 was
      detected in lung organogenesis. Several genes, such as Nkx2-5, Gata4, and Pitx2,
      were downregulated in the ECAT15-2-null lung. On the other hand, genomic DNA of
      these genes showed inactive chromatin statuses in ECAT15-2-null ESCs, but not in
      wild-type ESCs. The chromatin immunoprecipitation (ChIP) assay revealed that
      ECAT15-2 binds to the regulatory region of Nkx2-5 in ESCs. These data suggest
      that ECAT15-2 has important roles in lung development, where it is no longer
      expressed, by leaving epigenetic marks from earlier developmental stages.

PMID- 21896784
TI  - Motor chip: a comparative genomic hybridization microarray for copy-number
      mutations in 245 neuromuscular disorders.
AB  - BACKGROUND: Array-based comparative genomic hybridization (aCGH) is a reference
      high-throughput technology for detecting large pathogenic or polymorphic copy
      number variations in the human genome; however, a number of quantitative
      monogenic mutations, such as smaller heterozygous deletions or duplications, are
      usually missed in most disease genes when proper multiplex ligation-dependent
      probe assays are not performed. METHODS: We developed the Motor Chip, a
      customized CGH array with exonic coverage of 245 genes involved in neuromuscular
      disorders (NMDs), as well as 180 candidate disease genes. We analyzed DNA samples
      from 26 patients with known deletions or duplications in NMDs, 11 patients with
      partial molecular diagnoses, and 19 patients with a clinical diagnosis alone.
      RESULTS: The Motor Chip efficiently confirmed and refined the copy-number
      mutations in all of the characterized patients, even when only a single exon was
      involved. In noncharacterized or partially characterized patients, we found
      deletions in the SETX (senataxin), SGCG [sarcoglycan, gamma (35kDa dystrophin
      associated glycoprotein)], and LAMA2 (laminin, alpha 2) genes, as well as
      duplications involving LAMA2 and the DYSF [dysferlin, limb girdle muscular
      dystrophy 2B (autosomal recessive)] locus. CONCLUSIONS: The combination of exon
      specific gene coverage and optimized platform and probe selection makes the Motor
      Chip a complementary tool for molecular diagnosis and gene investigation in
      neuromuscular diseases.

PMID- 21896783
TI  - IRE1-dependent activation of AMPK in response to nitric oxide.
AB  - While there can be detrimental consequences of nitric oxide production at
      pathological concentrations, eukaryotic cells have evolved protective mechanisms
      to defend themselves against this damage. The unfolded-protein response (UPR),
      activated by misfolded proteins and oxidative stress, is one adaptive mechanism
      that is employed to protect cells from stress. Nitric oxide is a potent activator
      of AMP-activated protein kinase (AMPK), and AMPK participates in the cellular
      defense against nitric oxide-mediated damage in pancreatic beta-cells. In this
      study, the mechanism of AMPK activation by nitric oxide was explored. The known
      AMPK kinases LKB1, CaMKK, and TAK1 are not required for the activation of AMPK by
      nitric oxide. Instead, this activation is dependent on the endoplasmic reticulum
      (ER) stress-activated protein IRE1. Nitric oxide-induced AMPK phosphorylation and
      subsequent signaling to AMPK substrates, including Raptor, acetyl coenzyme A
      carboxylase, and PGC-1alpha, is attenuated in IRE1alpha-deficient cells. The
      endoribonuclease activity of IRE1 appears to be required for AMPK activation in
      response to nitric oxide. In addition to nitric oxide, stimulation of IRE1
      endoribonuclease activity with the flavonol quercetin leads to IRE1-dependent
      AMPK activation. These findings indicate that the RNase activity of IRE1
      participates in AMPK activation and subsequent signaling through multiple AMPK
      dependent pathways in response to nitrosative stress.

PMID- 21896785
TI  - A review of patient safety measures based on routinely collected hospital data.
AB  - The literature on patient safety measures derived from routinely collected
      hospital data was reviewed to inform indicator development. MEDLINE and Embase
      databases and Web sites were searched. Of 1738 citations, 124 studies describing
      the application, evaluation, or validation of hospital-based medical error or
      complication of care measures were reviewed. Studies were frequently conducted in
      the United States (n = 88) between 2005 and 2009 (n = 77) using Agency for
      Healthcare Research and Quality patient safety indicators (PSIs; n = 79). The
      most frequently cited indicators included "postoperative hemorrhage or hematoma"
      and "accidental puncture and laceration." Indicator refinement is supported by
      international coding algorithm translations but is hampered by data issues,
      including coding inconsistencies. The validity of PSIs and similar adverse event
      screens beyond internal measurement and the effects of organizational factors on
      patient harm remain uncertain. Development of PSIs in ambulatory care settings,
      including general practice and psychiatric care, needs consideration.

PMID- 21896786
TI  - Quality improvement "201": context-relevant quality improvement leadership
      training for the busy clinician-educator.
AB  - Development of quality improvement (QI) skills and leadership for busy clinician
      educators in academic medical centers is increasingly necessary, although it is
      challenging given limited resources. In response, the authors developed the
      Quality Scholars program for primary care teaching faculty. They conducted a
      needs assessment, evaluated existing internal and national resources, and
      developed a 9-month, 20-session project-based curriculum that combines didactic
      and hands-on techniques with facilitated project discussion. They also conducted
      pre-post tests of knowledge and attitudes, and evaluations of each session,
      scholars' projects, and program sustainability and costs. In all, 10 scholars
      from all 3 generalist disciplines comprised the first class. A wide spectrum of
      previous experiences enhanced collaboration. QI knowledge increased slightly, and
      reported self-readiness to lead QI projects increased markedly. Protected time
      for project work and group discussion of QI topics was seen as essential. All 10
      scholars completed projects and presented results. Institutional leadership
      agreed to sustain the program using institutional funds.

PMID- 21896787
TI  - The Mayo Clinic Value Creation System.
AB  - The authors present Mayo Clinic's Value Creation System, a coherent systems
      engineering approach to delivering a single high-value practice. There are 4
      tightly linked, interdependent phases of the system: alignment, discovery,
      managed diffusion, and measurement. The methodology is described and examples of
      the results to date are presented. The Value Creation System has been
      demonstrated to improve the quality of patient care while reducing costs and
      increasing productivity.

PMID- 21896788
TI  - Can response to induction chemotherapy be a predictive marker for ultimate
      outcome in hypopharyngeal cancer?
AB  - OBJECTIVE: Induction chemotherapy (ICT) may reduce rates of distant metastases
      and enhance organ preservation and survival rates in patients with hypopharyngeal
      cancer. The authors compared survival data in patients who underwent
      chemoradiotherapy or surgery after ICT and investigated whether response to ICT
      is a predictive marker for outcome in patients with hypopharyngeal cancer. STUDY
      DESIGN: Historical cohort study. SETTING: Tertiary-care hospital. SUBJECTS AND
      METHODS: The authors enrolled 97 patients (89 men, 8 women; mean age 61.2 years;
      range, 29-80 years) with previously untreated hypopharyngeal cancer who underwent
      ICT between January 1997 and December 2006 at Asan Medical Center. Disease-free
      survival (DFS), overall survival (OS), and laryngectomy-free survival (LFS) were
      analyzed. RESULTS: At a mean follow-up of 38.0 months, the 3-year DFS and OS for
      all patients were 48.3% and 49.2%, respectively. The 3-year LFS rate of patients
      who underwent nonsurgical therapy (n = 85) after ICT was 48.0%. Only response to
      ICT was associated with DFS (P = .047), OS (P = .003), and LFS (P = .009) in
      multivariate analysis. When the authors compared survival data in patients who
      underwent surgical and nonsurgical treatments after ICT, they found that there
      was no statistical difference in terms of the 3-year DFS in partial response
      (42.9% vs 50.5%, P = .77) and nonresponse groups (50.0% vs 0%, P = .43) between
      the 2 treatment types. CONCLUSION: ICT permits assessment of tumor responsiveness
      and alters subsequent therapy accordingly. Response to ICT may be useful in the
      prediction of ultimate outcomes and organ conservation in patients with
      hypopharyngeal cancer.

PMID- 21896789
TI  - Biosynthesis and identification of an N-oxide/N-glucuronide metabolite and first
      synthesis of an N-O-glucuronide metabolite of Lu AA21004.
AB  - This article describes the biosynthesis and identification of a new class of
      metabolites, a piperazine N-oxide/N-glucuronide metabolite 4-[2-(2,4-dimethyl
      phenylsulfanyl)-phenyl]-1-beta-D-glucuronic acid-piperazine 1-oxide (4). The
      metabolite was found in urine and plasma from humans and animals dosed with 1-[2
      (2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazine hydrobromide (Lu AA21004, 1), as
      a novel multimodal antidepressant under development for treatment of depression.
      Human liver microsomes in combination with uridine 5'-diphosphoglucuronic acid
      were used as an in vitro system to generate enough material of 4 to perform one-
      and two-dimensional (1)H and (13)C NMR experiments for structure elucidation.
      Based on rotating frame Overhauser enhancement spectroscopy NMR experiments, the
      distance correlation between a piperazine proton and the anomeric proton of the
      glucuronic acid moiety is of a magnitude similar to that of the H-3' and H-5'
      protons and can only be explained by proximity in space and the postulated
      structure (4). The structural analog, the N-O-glucuronic acid conjugate 6-{4-[2
      (2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazin-1-yloxy}-1-beta-D-glucuronic acid
      (3) was also observed in biological samples from humans and animals and the first
      organic synthesis and structural identification of this metabolite is also
      reported. Treatment of the glucuronide metabolites 3 and 4 with beta
      glucuronidase gave mainly the expected hydrolysis product, the hydroxyl amine 4
      [2-(2,4-dimethyl-phenylsulfanyl)-phenyl]-piperazin-1-ol (2).

PMID- 21896790
TI  - Twenty-five years of hidden profiles in group decision making: a meta-analysis.
AB  - This meta-analysis summarized findings from 65 studies using the hidden profile
      paradigm (101 independent effects, 3,189 groups). Results showed (a) groups
      mentioned two standard deviations more pieces of common information than unique
      information; (b) hidden profile groups were eight times less likely to find the
      solution than were groups having full information; (c) two measures of
      information pooling, including the percentage of unique information mentioned out
      of total available information (the information coverage measure) and the
      percentage of unique information out of total discussion (the discussion focus
      measure), were positively related to decision quality, but the effect of
      information coverage was stronger than that of discussion focus; and
      communication medium did not affect (d) unique information pooling or (e) group
      decision quality. Group size, total information load, the proportion of unique
      information, task demonstrability, and hidden profile strength were found to
      moderate these effects. Results are discussed in terms of how they offer
      conceptual advancement for future hidden profile research.

PMID- 21896791
TI  - The role of glucose in self-control: another look at the evidence and an
      alternative conceptualization.
AB  - The strength model suggests that self-control relies on a limited resource. One
      candidate for this resource is glucose. Counter to the proposals of the glucose
      hypothesis, this study argues that the resource issue is one of allocation, not
      of limited supply. It addresses the argument from three perspectives: the
      evolution of mental processes at the species level, the adaptation of these same
      processes at the individual level, and the physiology of glucose transport. It is
      argued here that the brain has both sufficient resources and resource delivery
      mechanisms with which to support self-control but that these resources are
      allocated in accordance with personal priorities. As an alternative to the
      limited resource model, the current study proposes a resource-allocation model of
      self-control and presents several testable hypotheses.

PMID- 21896792
TI  - Adult ascaris worm passing from the mouth.

PMID- 21896793
TI  - A truly emerging intestinal parasitosis.

PMID- 21896794
TI  - South-to-North, cross-disciplinary training in global health practice: ten years
      of lessons learned from an infectious disease field course in Jamaica.
AB  - Global commerce, travel, and emerging and resurging infectious diseases have
      increased awareness of global health threats and opportunities for collaborative
      and service learning. We review course materials, knowledge archives, data
      management archives, and student evaluations for the first 10 years of an
      intensive summer field course in infectious disease epidemiology and surveillance
      offered in Jamaica. We have trained 300 students from 28 countries through
      collaboration between the University of the West Indies and U.S. partner
      universities. Participants were primarily graduate students in public health, but
      also included health professionals with terminal degrees, and public health
      nurses and inspectors. Strong institutional synergies, committed faculty, an
      emphasis on scientific and cultural competencies, and use of team-based field
      research projects culminate in a unique training environment that provides
      participants with career-developing experiences. We share lessons learned over
      the past decade, and conclude that South-to-North leadership is critical in
      shaping transdisciplinary, cross-cultural, global health practice.

PMID- 21896795
TI  - Impact of global health residency training on medical knowledge of immigrant
      health.
AB  - Lack of global health knowledge places immigrants at risk of iatrogenic
      morbidity. Although global health education programs have grown in popularity,
      measurable impact is lacking. We previously surveyed 363 physicians in training
      across 15 programs in four countries in 2004 regarding basic parasite knowledge
      and recognition of Strongyloides risk through a theoretical case scenario. In
      2005, the University of Minnesota implemented a formal global health training
      program (GHP). In 2009, the identical survey was repeated. Strongyloidiasis
      recognition increased from 11.1% (19/171) in 2004 to 39.4% (50/127) in 2009 (P <
      0.001). Trainees participating in formal didactic and interactive curriculum had
      superior recognition (77% versus 29%; P < 0.001). In a multivariate model of GHP
      training activities, participation in an American Society of Tropical Medicine
      and Hygiene-accredited global health certificate course increased recognition
      (odds ratio = 9.5, 95% confidence interval = 2.5-36, P = 0.001), whereas
      participation in international electives alone did not (P = 0.9). A formal GHP
      curriculum was associated with improved knowledge regarding common parasitic
      infections and the risk of iatrogenic morbidity and mortality due to
      strongyloidiasis.

PMID- 21896796
TI  - Review and assessment of the American Society of Tropical Medicine and Hygiene
      travel awards program, 1991-2010.
AB  - During 1991-2010, 456 persons from 62 countries were provided financial support
      to attend the annual meeting of the American Society of Tropical Medicine and
      Hygiene. Winners came from 17 African, 16 Asia-Pacific, 14 Latin American and
      Caribbean, and 13 European and Middle Eastern countries, and from Canada and the
      United States. Virtually equal numbers of awards were offered to women and men.
      Winners were selected from U.S. academic centers (30%), foreign universities
      (26%), international centers, institutes or research units (30%), and
      approximately 5% from U.S. government agencies. Almost all winners (73 of 76,
      96%) had scientific publications subsequent to receiving the travel award. Less
      than 10% of award winners continued their membership in the Society after their
      one-year complementary membership. Winners indicated that the travel awards
      program facilitated international exchange and fostered collaborations between
      Society members and international scientists.

PMID- 21896797
TI  - Maternal anemia in Benin: prevalence, risk factors, and association with low
      birth weight.
AB  - We studied the prevalence of anemia during pregnancy and its relationship with
      low birth weight (LBW; birth weight < 2,500 g) in Benin. We analyzed 1,508
      observations from a randomized controlled trial conducted from 2005 to 2008
      showing equivalence on the risk of LBW between two drugs for Intermittent
      Preventive Treatment of malaria during pregnancy (IPTp). Despite IPTp, helminth
      prophylaxis, and iron and folic acid supplementations, the proportions of women
      with severe anemia (hemoglobin [Hb] concentration < 80 g/L) and anemia (Hb < 110
      g/L) were high throughout pregnancy: 3.9% and 64.7% during the second and 3.7%
      and 64.1% during the third trimester, but 2.5% and 39.6% at the onset of labor,
      respectively. Compared with women without anemia (Hb >= 110 g/L) during the third
      trimester, women with severe anemia (Hb < 80 g/L) were at higher risk of LBW
      after adjustment for potential confounding factors (prevalence ratio [PR] = 2.8;
      95% confidence interval [1.4-5.6]).

PMID- 21896798
TI  - Competency of reptiles and amphibians for eastern equine encephalitis virus.
AB  - Eastern equine encephalitis virus (EEEV) is endemic throughout most of the
      eastern United States. Although it is transmitted year round in Florida,
      transmission elsewhere is seasonal. The mechanism that enables EEEV to overwinter
      in seasonal foci remains obscure. In previous field studies, early season EEEV
      activity was detected in mosquito species that feed primarily upon ectothermic
      hosts, suggesting that reptiles and amphibians might represent overwintering
      reservoir hosts for EEEV. To determine if this might be possible, two commonly
      fed upon amphibian and reptile species were evaluated as hosts for the North
      American subtype I strain of EEEV. Neither amphibian species was a competent
      host. However, circulating viremias were detected in both reptile species
      examined. Hibernating infected garter snakes remained viremic after exiting
      hibernation. These data suggest that snakes may represent an overwintering host
      for North American EEEV.

PMID- 21896799
TI  - West Nile virus vector competency of Culex quinquefasciatus mosquitoes in the
      Galapagos Islands.
AB  - The mosquito-transmitted pathogen West Nile virus (WNV) is not yet present in the
      Galapagos Archipelago of Ecuador. However, concern exists for fragile endemic
      island fauna after population decreases in several North American bird species
      and pathology in certain reptiles. We examined WNV vector competency of a
      Galapagos strain of mosquito (Culex quinquefasciatus Say). Field specimens were
      tested for their capacity to transmit the WN02-1956 strain of WNV after
      incubation at 27 degrees C or 30 degrees C. Rates of infection, dissemination,
      and transmission all increased with days post-exposure to WNV, and the highest
      rates were observed at 28 days. Infection rates peaked at 59% and transmission
      rates peaked at 44% (of mosquitoes tested). Vector efficiency increased after day
      14. Rates of infection but not of transmission were significantly influence by
      temperature. No vertical transmission was detectable. We demonstrate that
      Galapagos Cx. quinquefasciatus are competent WNV vectors, and therefore should be
      considered an animal and public health risk for the islands and controlled
      wherever possible.

PMID- 21896800
TI  - Reexamination of Culex pipiens hybridization zone in the Eastern United States by
      ribosomal DNA-based single nucleotide polymorphism markers.
AB  - Mosquitoes in the Culex pipiens complex are important vectors of several disease
      causing pathogens, including West Nile virus. In North America, the complex
      consists of Cx. pipiens pipiens form pipiens, Cx. pipiens pipiens form molestus,
      Cx. pipiens quinquefasciatus, and their hybrids that exhibit substantial
      diversity in physiology, behavior, and geographic range. Hybridization among
      these mosquitoes is of concern because of potential implications for disease
      transmission. Currently, several morphological and molecular markers exist for
      differentiating members of the Cx. pipiens complex; however, these markers have
      specific limitations. We report here two highly reliable ribosomal DNA-based
      single nucleotide polymorphism (SNP) markers, CxpG2T and CxpA2d, for detecting
      Cx. pipiens complex mosquitoes containing Cx. p. quinquefasciatus alleles. Both
      CxpG2T and CxpA2d contain one allele that is present in all members of the Cx.
      pipiens complex, and the other allele is specific to Cx. p. quinquefasciatus.
      Testing of field populations from the eastern United States showed that these two
      SNP markers are capable of identifying a south to north gradient of Cx. p.
      quinquefasciatus and hybrids. The northern limit of detection of Cx. p.
      quinquefasciatus alleles in this study was in Fort Totten, NY (40.79 degrees N),
      whereas the southern boundary was determined between Atlanta, GA (33.81 degrees
      N) and Gainesville, FL (29.64 degrees N). CxpG2T and CxpA2d were more accurate
      than the ACE-2 marker, and they may conceivably provide comparable resolution
      with microsatellite markers for detecting Cx. p. quinquefasciatus alleles.

PMID- 21896801
TI  - Circulation of diverse genotypes of Tahyna virus in Xinjiang, People's Republic
      of China.
AB  - Tahyna virus (TAHV) is widely distributed in Europe and Asia. A previous study
      reported a high level of conservation of the TAHV genome in isolates from Europe.
      During 2006 and 2007, three Tahyna virus isolates from mosquitoes were obtained
      from various locations in Xinjiang, People's Republic of China. We analyzed the
      complete coding sequence of full-length small, medium, and large segments of
      these isolates. Molecular and phylogenetic analyses of the three complete TAHV
      genomes showed that sequence identity between isolates from China and Europe was
      more divergent, and an unexpected level of medium segment diversity was found
      among isolates from China compared with high levels of sequence conservation for
      the small and large segments. This study indicated that effects of genotypic
      diversity on the ecology, transmission, and pathogenicity of TAHV in China should
      be studied.

PMID- 21896802
TI  - Vector competence of Australian mosquitoes for yellow fever virus.
AB  - The vector competence of Australian mosquitoes for yellow fever virus (YFV) was
      evaluated. Infection and transmission rates in Cairns and Townsville populations
      of Aedes aegypti and a Brisbane strain of Ae. notoscriptus were not significantly
      different from a well-characterized YFV-susceptible strain of Ae. aegypti. After
      exposure to 107.2 tissue culture infectious dose (TCID50)/mL of an African strain
      of YFV, > 70% of Ae. aegypti and Ae. notoscriptus became infected, and > 50%
      transmitted the virus. When exposed to 106.7) TCID50/mL of a South American
      strain of YFV, the highest infection (64%) and transmission (56%) rates were
      observed in Ae. notoscriptus. The infection and transmission rates in the Cairns
      Ae. aegypti were both 24%, and they were 36% and 28%, respectively, for the
      Townsville population. Because competent vectors are present, the limited number
      of travelers from endemic areas and strict vaccination requirements will
      influence whether YFV transmission occurs in Australia.

PMID- 21896803
TI  - Demographic and clinical characteristics of patients with anaphylactic shock
      after surgery for cystic echinococcosis.
AB  - We reviewed the records of 446 patients who were treated surgically for cystic
      echinococcosis (CE) to identify risk factors for anaphylactic shock. Of 446
      patients, 10 had final diagnoses of anaphylactic shock induced by CE; none died.
      The incidence of anaphylactic shock was significantly higher in younger age
      groups (P < 0.001) and in patients with pulmonary cysts. Anaphylactic shock
      induced by CE appears to differ from type I immediate hypersensitivity shock,
      which suggests that in CE, shock may be caused by a combination of immediate
      hypersensitivity and endotoxic shock. This possibility suggests that additional
      precautions should be taken during surgery. These precautions include reducing
      intracystic pressure, which would prevent possible leaked liquid from reaching
      other organs by surrounding the cyst with sterile gauze and decrease the chance
      of spreading the echinococcus; preventing antigen from contacting other tissues
      where it might trigger anaphylaxis; and resecting the cyst completely when
      feasible.

PMID- 21896804
TI  - A case of pulmonary and hepatic cystic Echinococcosis of CE1 stage in a healthy
      Japanese female that was suspected to have been acquired during her stay in the
      United Kingdom.
AB  - We herein report a case of a young Japanese female who was confirmed to have
      cystic echinococcosis (CE) 1 stage based on the World Health Organization
      Informal Working Group on Echinococcosis pathological classification of CE, and
      she was also suspected to be infected with eggs of the G1 Echinococcus granulosus
      sensu stricto during her stay in the United Kingdom and therefore, suffered from
      synchronous pulmonary and hepatic CE. Oral albendazole was administered
      initially, but rupture of a lung hydatid cyst was observed. To avoid additional
      rupture, we performed two surgeries. CE is very rare in Japan; all CE cases in
      Japan during the past two decades have been confirmed to be imported, and almost
      all cases are hepatic CE. This case is the first case report of a Japanese
      patient who had concomitant giant lung and liver CE with early-stage CE1 and was
      successfully treated by surgery and pharmacotherapy with a serological follow-up.

PMID- 21896805
TI  - Short report: A calcified Taenia solium granuloma associated with recurrent
      perilesional edema causing refractory seizures: histopathological features.
AB  - We describe the first detailed histological description of an excised calcified
      Taenia solium granuloma from a patient who developed recurrent seizures
      associated with perilesional edema surrounding a calcified cysticercus (PEC). The
      capsule, around a degenerated cysticercus, contained marked mononuclear
      infiltrates that extended to adjacent brain, which showed marked astrocytosis,
      microgliosis, and inflammatory perivascular infiltrates. The presence of large
      numbers of mononuclear cells supports an inflammatory cause of PEC.
      Immunosuppression or anti-inflammatory measures may be able to treat and prevent
      PEC and recurrent seizures.

PMID- 21896806
TI  - Serum antibody responses to polymorphic Cryptosporidium mucin antigen in
      Bangladeshi children with cryptosporidiosis.
AB  - Cryptosporidium is a significant cause of diarrheal disease in children in
      developing countries. The sporozoite antigen Muc4 is important for infection of
      host cells, and could be a candidate vaccine antigen. However, this antigen is
      polymorphic between Cryptosporidium hominis and C. parvum. We investigated
      antibody responses to C. hominis Muc4 and C. parvum Muc4 antigen in children in
      Bangladesh infected with C. hominis. Antibody responses were compared between
      children with cryptosporidial diarrhea (cases) and uninfected children with
      diarrhea (controls). There was a significant IgM response to Muc4 from both
      species in cases compared with controls, which increased over time, and was
      higher in children with persistent diarrhea. Despite sequence polymorphisms,
      antibody responses to C. hominis Muc4 and C. parvum Muc4 were significantly
      correlated. These results suggest that the human antibody response to Muc4 is
      cross-reactive between species, but in young children does not mature to an IgG
      response within the period observed in this study.

PMID- 21896807
TI  - Leptospirosis outbreak in Sri Lanka in 2008: lessons for assessing the global
      burden of disease.
AB  - Global leptospirosis disease burden estimates are hampered by the lack of
      scientifically sound data from countries with probable high endemicity and
      limited diagnostic capacities. We describe the seroepidemiologic and clinical
      characteristics of the leptospirosis outbreak in 2008 in Sri Lanka.
      Definitive/presumptive case definitions proposed by the World Health Organization
      Leptospirosis Epidemiology Reference Group were used for case confirmation. Of
      the 404 possible cases, 155 were confirmed to have leptospirosis. Highest titers
      of patient seum samples reacted with serovars Pyrogenes (28.7%), Hardjo (18.8%),
      Javanica (11.5%), and Hebdomadis (11.5%). Sequencing of the 16S ribosomal DNA
      gene identified six infections: five with Leptospira interrogans and one with L.
      weilli. In this patient population, acute renal failure was the main complication
      (14.8%), followed by myocarditis (7.1%) and heart failure (3.9%). The case
      fatality rate was 1.3%. This report strengthens the urgent need for increasing
      laboratory diagnostic capabilities to determine the causes of epidemic and
      endemic infectious diseases in Sri Lanka, a finding relevant to other tropical
      regions.

PMID- 21896808
TI  - Different patterns in a cohort of patients with severe leptospirosis (Weil
      syndrome): effects of an educational program in an endemic area.
AB  - The aim of this study is to investigate the changes in clinical pattern and
      therapeutic measures in leptospirosis-associated acute kidney injury; a
      retrospective study with 318 patients in Brazil. Patients were divided according
      to the time of admission: 1985-1996 (group I) and 1997-2010 (group II). Patients
      were younger in group I (36 +/- 13 versus 41 +/- 16 years, P = 0.005) and the
      numbers of oliguria increased (21% versus 41% in group II, P = 0.014). Higher
      frequency of lung manifestations was observed in group II (P < 0.0001). Although
      increased severity, there was a significant reduction in mortality (20% in group
      I versus 12% in group II, P = 0.03). Mortality was associated with advanced age,
      low diastolic blood pressure, oliguria, arrhythmia, and peritoneal dialysis,
      besides a trend to better mortality with penicillin administration. Leptospirosis
      is occurring in an older population, with a higher number of oliguria and lung
      manifestations. However, mortality is decreasing and can be the result of changes
      in treatment.

PMID- 21896809
TI  - Evaluation of Pichia pastoris-expressed recombinant rhoptry protein 2 of
      Toxoplasma gondii for its application in diagnosis of toxoplasmosis.
AB  - Rhoptry protein 2 (ROP2) of Toxoplasma gondii is a rhoptry-secreted protein that
      plays a critical role in parasitophorous vacuole membrane formation during
      invasion. In previous studies, ROP2 has been shown to be efficient in triggering
      humoral and cell-mediated responses. High immunogenicity of ROP2 makes it a
      potential candidate for diagnosis and vaccination against toxoplasmosis. In this
      study, the ROP2 gene was cloned into pPICZalpha A expression vector and
      extracellularly expressed in the yeast Pichia pastoris, which has numerous
      advantages over other expression systems for eukaryotic proteins expression. The
      effectiveness of the secreted recombinant ROP2 as a diagnosis agent was assessed
      by Western Blot with 200 human serum samples. Recombinant ROP2 reacted with
      toxoplasmosis-positive human serum samples and yielded an overall sensitivity of
      90% and specificity of 95%. However, recombinant ROP2 is a better marker for
      detection of IgG (91.7%) rather than IgM (80%).

PMID- 21896810
TI  - Entomological indices, feeding sources, and molecular identification of Triatoma
      phyllosoma (Hemiptera: Reduviidae) one of the main vectors of Chagas disease in
      the Istmo de Tehuantepec, Oaxaca, Mexico.
AB  - The purpose of this study was to conduct an entomological analysis, determination
      of feeding sources, and molecular identification of triatomines in five
      communities of the Istmo de Tehuantepec, Oaxaca. The only found species in two of
      five searched communities (San Mateo del Mar and Tehuantepec City) was Triatoma
      phyllosoma. Colonization indices were high in both communities. In San Mateo del
      Mar, the insects were found indoors and in Tehuantepec City in peridomestic
      areas. The Trypanosoma cruzi infection indices were 2.1% in San Mateo del Mar and
      39.4% in Tehuantepec City. This difference could be related to the high numbers
      of triatomine feeding on hens in the former community. In contrast, in
      Tehuantepec, dogs were the principal triatomine feeding sources. All nymphs and
      adults that were genetically analyzed belonged to the species T. phyllosoma. Low
      levels of genetic variation were found between vectors from both communities.

PMID- 21896811
TI  - Social ecological analysis of an outbreak of pufferfish egg poisoning in a
      coastal area of Bangladesh.
AB  - Recurrent outbreaks of marine pufferfish poisoning in Bangladesh highlight the
      need to understand the context in which the outbreaks occurred. In a recent
      outbreak investigation, a multidisciplinary team conducted a mixed-method study
      to identify the demography and clinical manifestation of the victims and to
      explore different uses of pufferfish, and local buying, selling, and processing
      practices. The outbreak primarily affected a low income household where an
      elderly woman collected and cooked pufferfish egg curry. Nine persons consumed
      the curry, and symptoms developed in 6 (67%) of these persons. Symptoms included
      vomiting, diarrhea, paresis, and tingling sensation; 2 (22%) persons died. The
      unstable income of the affected family, food crisis, and the public disposal of
      unsafe pufferfish byproducts all contributed to the outbreak. A multi-level
      intervention should be developed and disseminated with the participation of
      target communities to discourage unsafe discarding of pufferfish scraps and to
      improve the community knowledge about the risk of consuming pufferfish.

PMID- 21896812
TI  - Exploratory study on pathogenesis of far-eastern spotted fever.
AB  - Far-eastern spotted fever is an emerging disease caused by Rickettsia
      heilongjiangensis, a tick-borne obligate intracellular bacterium. In this study,
      R. heilongjiangensis was used to infect BALB/c mice by inoculation of retro
      orbital venous plexus to imitate a blood infection caused by tick biting. We
      found that R. heilongjiangensis rapidly entered the circulation for systemic
      dissemination and the pathogen existed in liver, spleen, lungs, and brain of the
      mice at least 9 days post-infection (p.i.). Severe pathological lesions were
      observed in liver, lungs, and brain at Day 6 p.i. In addition, the elevated
      levels of inflammatory cytokines, including interferon-gamma, tumor necrosis
      factor, and CC chemokine, were detected in the infected organs at Day 3 p.i. Our
      results reveal that R. heilongjiangensis may cause an infection in BALB/c mice
      and the pathological lesions in the infected mice are associated with host
      inflammatory response induced by R. heilongjiangensis.

PMID- 21896813
TI  - Short report: Identification of virulence-associated plasmids in Rhodococcus equi
      in humans with and without acquired immunodeficiency syndrome in Brazil.
AB  - Virulence of Rhodococcus equi strains from 20 humans in Brazil was investigated
      by using a polymerase chain reaction to characterize isolates as virulent (VapA),
      intermediately virulent (VapB), and avirulent. Nine isolates were obtained from
      human immunodeficiency virus (HIV)-positive patients, six from HIV-negative
      patients, and five from patients of unknown status. Five isolates were VapB
      positive, four were VapA positive, and eleven were avirulent. Among the nine
      isolates from HIV-positive patients, five contained VapB plasmids and two
      contained VapA plasmids. Five VapB-positive isolates had the type 8 virulence
      plasmid. Eleven of the patients had a history of contact with livestock and/or a
      farm environment, and none had contact with pigs.

PMID- 21896814
TI  - Short report: Gender differences in tuberculosis notification in Pakistan.
AB  - Worldwide, the male to female ratio of new smear-positive tuberculosis (TB) cases
      is approximately two to one. However, in Pakistan, this is not the case. Rates of
      notified TB cases are 20-30% higher in young females compared with males, and
      female rates remain high regardless of increasing age. This is in stark contrast
      to neighboring India, which is characterized by an excess of male TB cases. It is
      currently unknown why rates of notified TB are so high in females in Pakistan,
      but it is clear that this epidemiology is a public health issue of importance
      that impacts transmission dynamics and disease control initiatives.

PMID- 21896815
TI  - Latrine promotion for trachoma: assessment of mortality from a cluster-randomized
      trial in Ethiopia.
AB  - Trachoma control strategies, including latrine construction and antibiotic
      distribution, are directed at reducing ocular chlamydia, but may have additional
      benefits. In a cluster-randomized clinical trial, 24 subkebeles (administrative
      geographic units) in Ethiopia were offered a single mass azithromycin treatment,
      and half were randomized to receive an intensive latrine promotion. At a follow
      up census 26 months after the baseline treatment, 320 persons had died. The
      mortality rate of children 1-5 years of age was 3.87 (95% confidence interval
      [CI] = 2.19-6.82) per 1,000 person-years in the latrine promotion arm, and 2.72
      (95% CI = 1.37-5.42) per 1,000 person-years in the control arm. In a multi-level
      mixed effects logistic regression model controlling for age, there was no
      difference in mortality in persons randomized into the latrine or control arms
      (odds ratio = 1.18, 95% CI = 0.89-1.58). Latrine promotion provided no additional
      effect on mortality in the context of an azithromycin distribution program
      (clinicaltrials.gov, #NCT00322972).

PMID- 21896816
TI  - American tegumentary leishmaniasis and HIV-AIDS association in a tertiary care
      center in the Brazilian Amazon.
AB  - American tegumentary leishmaniasis (ATL) and human immunodeficiency virus (HIV)
      are both common infectious diseases in the Brazilian Amazon with overlapping
      expansion areas, which leads to the occurrence of Leishmania/HIV coinfection.
      Most ATL/HIV-acquired immunodeficiency syndrome (AIDS) association cases have
      been reported from areas where Leishmania (Viannia) braziliensis is the main
      pathogen; this finding is in contrast with the Amazon region, where L. (V.)
      guyanensis is the most implicated agent, implying distinct clinical and
      therapeutic aspects. We describe 15 cases of ATL/HIV coinfection treated in a
      tertiary care center in the Brazilian Amazon between 1999 and 2008. Thirteen
      patients presented with diverse clinical manifestations of cutaneous
      leishmaniasis, and four of them had disseminated forms; two patients presented
      with mucosal leishmaniasis (ML). Seven patients required more than one course of
      treatment. The particularities of ATL/HIV-AIDS association in L. (V.) guyanensis
      endemic areas require efforts for an increased understanding of its burden and
      subsequent improvements in case management.

PMID- 21896817
TI  - Economic consequences of post-kala-azar dermal leishmaniasis in a rural
      Bangladeshi community.
AB  - Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral
      leishmaniasis. Bangladesh national treatment guidelines during the study period
      called for 120 intramuscular injections of sodium antimony gluconate (SAG). We
      assessed care-seeking behavior, diagnosis and treatment costs, and coping
      strategies among 134 PKDL patients; 56 (42%) patients had been treated with SAG,
      and 78 (58%) remained untreated. The median direct cost per patient treated was
      US$367 (interquartile range [IQR] = 90-284), more than two times the estimated
      per capita annual income for the study population. The most common coping
      strategy was to take a loan; the median amount borrowed was US$98 (IQR = 71-150),
      with a median interest of US$32 (IQR = 16-95). Households lost a median of 123
      work-days per patient treated. The current regimen for PKDL imposes a significant
      financial burden, reinforcing the link between poverty and visceral
      leishmaniasis. More practical shorter-course regimens for PKDL are urgently
      needed to achieve national and regional visceral leishmaniasis elimination goals.

PMID- 21896818
TI  - Adipose tissue-derived mesenchymal stem cells as a new host cell in latent
      leishmaniasis.
AB  - Some protozoan infections such as Toxoplasma, Cryptosporidium, and Plasmodium can
      be transmitted through stem cell transplantations. To our knowledge, so far,
      there is no study about transmission of Leishmania parasites in stem cell
      transplantation and interactions between parasites and stem cells in vitro.
      Therefore, the aim of this study was to investigate the interaction between
      different species of Leishmania parasites and adipose tissue-derived mesenchymal
      stem cells (ADMSCs). ADMSCs have been isolated, cultured, characterized, and
      infected with different species of Leishmania parasites (L. donovani, L. major,
      L. tropica, and L. infantum). Infectivity was examined by Giemsa staining,
      microculture, and polymerase chain reaction methods. As a result, infectivity of
      ADMSCs by Leishmania parasites has been determined for the first time in this
      study. According to our findings, it is very important that donors are screened
      for Leishmania parasites before stem cell transplantations in regions where
      leishmaniasis is endemic.

PMID- 21896819
TI  - Short report: Genetic diversity of Thottapalayam virus, a Hantavirus harbored by
      the Asian house shrew (Suncus murinus) in Nepal.
AB  - Despite the recent discovery of genetically divergent hantaviruses in shrews of
      multiple species in widely separated geographic regions, data are unavailable
      about the genetic diversity and phylogeography of Thottapalayam virus (TPMV), a
      hantavirus originally isolated from an Asian house shrew (Suncus murinus)
      captured in southern India more than four decades ago. To bridge this knowledge
      gap, the S, M, and L segments of hantavirus RNA were amplified by reverse
      transcription polymerase chain reaction from archival lung tissues of Asian house
      shrews captured in Nepal from January to September 1996. Pair-wise alignment and
      comparison revealed approximately 80% nucleotide and > 94% amino acid sequence
      similarity to prototype TPMV. Phylogenetic analyses, generated by maximum
      likelihood and Bayesian methods, showed geographic-specific clustering of TPMV,
      similar to that observed for rodent- and soricid-borne hantaviruses. These
      findings confirm that the Asian house shrew is the natural reservoir of TPMV and
      suggest a long-standing virus-host relationship.

PMID- 21896820
TI  - Paracoccidioidomycosis epidemiological features of a 1,000-cases series from a
      hyperendemic area on the southeast of Brazil.
AB  - Paracoccidioidomycosis has been known for over 100 years, and until now, there
      were only few estimates of the disease's incidence. We aim to analyze 1,000 cases
      treated between 1960 and 1999 at Ribeirao Preto city, Sao Paulo, Brazil, where
      the disease's incidence range detected was 1.6 to 3.7 cases per 100,000 habitants
      per year (mean = 2.7 cases/year). We observed a male to female ratio of 6:1 and
      an age distribution from 3 to 85 years. The acute/subacute form of the disease
      accounted for 25.4% of cases. Most of the patients (93.5%) had lived or worked in
      rural areas before the disease development. Smoking and alcoholism were reported
      by 64.7% and 37.2% of patients, respectively. Comorbidities identified included
      tuberculosis (8.3%), Chagas' disease (8.6%), and human immunodeficiency
      virus/acquired immunodeficiency syndrome (4.2%). The present study revealed an
      area in Brazil where paracoccidioidomycosis is hyperendemic (has the highest
      reported incidence of this disease); this endemic area is probably caused by
      geological and climatic conditions as well as intensive agriculture.

PMID- 21896821
TI  - Isolation of usutu virus in Germany.
AB  - Usutu virus (USUV) is a mosquito-borne flavivirus that emerged 2001 in Austria
      and caused deaths in wild birds. In Germany, 70,378 female mosquitoes were
      captured in 2009 and 2010 and assayed for USUV. Virus was isolated in cell
      culture from one pool of Culex pipiens pipiens mosquitoes trapped exclusively in
      August 2010 in Weinheim, Germany. Subsequent phylogenetic analysis demonstrated a
      close relationship between the isolated USUV strain from Germany and a USUV
      strain from Austria, which was detected in a dead blackbird in 2004.

PMID- 21896822
TI  - Malaria in the Republic of Djibouti, 1998-2009.
AB  - Historically, native populations in the Republic of Djibouti have experienced
      only low and unstable malaria transmission and intermittent epidemics. In recent
      years, efforts at malaria control have been aggressively pursued. This study was
      performed to inform revised malaria prevention recommendations for military
      service members and international travelers to the country. Laboratory-confirmed
      cases of malaria documented at large medical facilities and within military and
      civilian health care systems in the Republic of Djibouti from 1998 to 2009 were
      reviewed. In recent years, fewer than 5% of febrile cases among the three largest
      passive surveillance systems were laboratory-confirmed as malaria, and incidence
      of confirmed malaria was well below 1/1,000 persons/year. As efforts in the
      Republic of Djibouti progress toward elimination, and in conjunction with
      continued efforts at surveillance, emphasizing mosquito-avoidance measures and
      standby emergency treatment will become reasonable recommendations for malaria
      prevention.

PMID- 21896823
TI  - Meteorological factors-based spatio-temporal mapping and predicting malaria in
      central China.
AB  - Despite significant reductions in the overall burden of malaria in the 20th
      century, this disease still represents a significant public health problem in
      China, especially in central areas. Understanding the spatio-temporal
      distribution of malaria is essential in the planning and implementing of
      effective control measures. In this study, normalized meteorological factors were
      incorporated in spatio-temporal models. Seven models were established in WinBUGS
      software by using Bayesian hierarchical models and Markov Chain Monte Carlo
      methods. M1, M2, and M3 modeled separate meteorological factors, and M3, which
      modeled rainfall performed better than M1 and M2, which modeled average
      temperature and relative humidity, respectively. M7 was the best fitting models
      on the basis of based on deviance information criterion and predicting errors.
      The results showed that the way rainfall influencing malaria incidence was
      different from other factors, which could be interpreted as rainfall having a
      greater influence than other factors.

PMID- 21896824
TI  - Polymorphisms of molecular markers of antimalarial drug resistance and
      relationship with artesunate-mefloquine combination therapy in patients with
      uncomplicated Plasmodium falciparum malaria in Thailand.
AB  - The aim of this study was to investigate the association between genetic
      polymorphisms of Plasmodium falciparum chloroquine resistance transporter
      (pfcrt), P. falciparum multidrug resistance 1 (pfmdr1), and P. falciparum ATPase
      (pfatp6) and clinical outcome after a three-day mefloquine-artesunate combination
      therapy in 134 patients with uncomplicated Plasmodium falciparum malaria in an
      area with multidrug resistance along the Thailand-Myanmar border. Analysis of
      gene mutation and amplification were performed by nested real-time polymerase
      chain reaction and SYBR Green I real-time polymerase chain reaction,
      respectively. The mutation for pfcrt (codons 76, 220, 271, 326, 356, and 371) was
      found in all isolates (100%), whereas no mutation of pfmdr1 (codon 86) and pfatp6
      (codons 37, 693, 769, 898) was found. The Pfmdr1 copy number was significantly
      higher in isolates with recrudescence (median number = 2.44) compared with a
      sensitive response (median number = 1.44). The gene copy number was also found to
      be significantly higher in paired isolates collected before treatment and at the
      time of recrudescence. All isolates carried one pfatp6 gene copy.

PMID- 21896825
TI  - Efficacy and effectiveness of mefloquine and artesunate combination therapy for
      uncomplicated Plasmodium falciparum malaria in the Peruvian Amazon.
AB  - We evaluated the efficacy and effectiveness of mefloquine (MQ) plus artesunate
      (AS) to treat patients with uncomplicated malaria in the Peruvian Amazon Basin in
      April 2005-March 2006. Patients >= 1 year of age with fever (axillary temperature
      >= 37.5 degrees C) or history of fever and Plasmodium falciparum monoinfection
      were included. Patients received antimalarial treatment with MQ (12.5 mg/kg/day
      for two days) and AS (4.0 mg/kg/day for three days) either by directly observed
      therapy or without directly observed therapy. After a 28-day follow-up, treatment
      efficacy and effectiveness were assessed on the basis of clinical and
      parasitologic outcomes. Ninety-six patients were enrolled in each study group;
      nine patients were lost to follow-up. All patients, except for one in the
      observed group, demonstrated adequate clinical and parasitologic response; none
      had detectable parasitemia on day 3. The efficacy of MQ + AS efficacy was 98.9%
      (95% confidence interval = 94.1-100.0%) and the effectiveness was 100.0% (95%
      confidence interval = 95.9-100.0%). Our study shows that MQ + AS is highly
      efficacious in the Peruvian Amazon.

PMID- 21896826
TI  - The appropriate indicator should be used to assess treatment failure in STH
      infections.

PMID- 21896828
TI  - Model to predict mortality in critically ill adults with acute kidney injury.
AB  - BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) requiring dialysis is
      associated with high mortality. Most prognostic tools used to describe case
      complexity and to project patient outcome lack predictive accuracy when applied
      in patients with AKI. In this study, we developed an AKI-specific predictive
      model for 60-day mortality and compared the model to the performance of two
      generic (Sequential Organ Failure Assessment [SOFA] and Acute Physiology and
      Chronic Health Evaluation II [APACHE II]) scores, and a disease specific
      (Cleveland Clinic [CCF]) score. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:
      Data from 1122 subjects enrolled in the Veterans Affairs/National Institutes of
      Health Acute Renal Failure Trial Network study; a multicenter randomized trial of
      intensive versus less intensive renal support in critically ill patients with AKI
      conducted between November 2003 and July 2007 at 27 VA- and university-affiliated
      centers. RESULTS: The 60-day mortality was 53%. Twenty-one independent predictors
      of 60-day mortality were identified. The logistic regression model exhibited good
      discrimination, with an area under the receiver operating characteristic (ROC)
      curve of 0.85 (0.83 to 0.88), and a derived integer risk score yielded a value of
      0.80 (0.77 to 0.83). Existing scoring systems, including APACHE II, SOFA, and
      CCF, when applied to our cohort, showed relatively poor discrimination, reflected
      by areas under the ROC curve of 0.68 (0.64 to 0.71), 0.69 (0.66 to 0.73), and
      0.65 (0.62 to 0.69), respectively. CONCLUSIONS: Our new risk model outperformed
      existing generic and disease-specific scoring systems in predicting 60-day
      mortality in critically ill patients with AKI. The current model requires
      external validation before it can be applied to other patient populations.

PMID- 21896831
TI  - New CJASN feature: public policy series.

PMID- 21896830
TI  - Primary hyperoxaluria type III gene HOGA1 (formerly DHDPSL) as a possible risk
      factor for idiopathic calcium oxalate urolithiasis.
AB  - BACKGROUND AND OBJECTIVES: Primary hyperoxaluria types I and II (PHI and PHII)
      are rare monogenic causes of hyperoxaluria and calcium oxalate urolithiasis.
      Recently, we described type III, due to mutations in HOGA1 (formerly DHDPSL),
      hypothesized to cause a gain of mitochondrial 4-hydroxy-2-oxoglutarate aldolase
      activity, resulting in excess oxalate. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: To further explore the pathophysiology of HOGA1, we screened
      additional non-PHI-PHII patients and performed reverse transcription PCR
      analysis. Postulating that HOGA1 may influence urine oxalate, we also screened
      100 idiopathic calcium oxalate stone formers. RESULTS: Of 28 unrelated
      hyperoxaluric patients with marked hyperoxaluria not due to PHI, PHII, or any
      identifiable secondary cause, we identified 10 (36%) with two HOGA1 mutations
      (four novel, including a nonsense variant). Reverse transcription PCR of the stop
      codon and two common mutations showed stable expression. From the new and our
      previously described PHIII cohort, 25 patients were identified for study. Urine
      oxalate was lower and urine calcium and uric acid were higher when compared with
      PHI and PHII. After 7.2 years median follow-up, mean eGFR was 116 ml/min per 1.73
      m(2). HOGA1 heterozygosity was found in two patients with mild hyperoxaluria and
      in three of 100 idiopathic calcium oxalate stone formers. No HOGA1 variants were
      detected in 166 controls. CONCLUSIONS: These findings, in the context of
      autosomal recessive inheritance for PHIII, support a loss-of-function mechanism
      for HOGA1, with potential for a dominant-negative effect. Detection of HOGA1
      variants in idiopathic calcium oxalate urolithiasis also suggests HOGA1 may be a
      predisposing factor for this condition.

PMID- 21896832
TI  - Better off living--the ethics of the new UNOS proposal for allocating kidneys for
      transplantation.

PMID- 21896833
TI  - Ethical principles and processes guiding dialysis decision-making.
AB  - When the US Congress created the End-Stage Renal Disease (ESRD) Program in 1972,
      it gave physicians the responsibility of determining which patients were
      "appropriate" for dialysis. Congress provided no guidance on who should be
      selected or how. Only five years later, Dr. Belding Scribner, the father of
      chronic dialysis, noted that there was a need for a "deselection committee"
      because virtually all criteria for dialysis patient selection had been slackened,
      if not abandoned. In 1991, the Institute of Medicine Committee to Study the
      Medicare ESRD Program recommended the development of a clinical practice
      guideline because they noted there were "an increasing number of [dialysis]
      patients with limited survival possibilities and relatively poor quality of
      life." In 2000, the Renal Physicians Association and the American Society of
      Nephrology heeded the Institute of Medicine committee's recommendation and
      published Shared Decision-Making in the Appropriate Initiation of and Withdrawal
      from Dialysis. In 2010, prompted by a substantial body of new research evidence,
      the Renal Physicians Association published a second edition of this clinical
      practice guideline. This article describes the application of the ethical
      principles of respect for patient autonomy, beneficence, nonmaleficence, justice,
      and professional integrity, and the ethical process of shared decision-making in
      making decisions about starting, withholding, continuing, and stopping dialysis
      with patients and families. It urges examination of medical indications and
      identifies appropriate limits to shared decision-making when the burdens of
      dialysis can be predicted to substantially outweigh the benefits.

PMID- 21896834
TI  - The 2010 nephrology quiz and questionnaire: part 1.
AB  - Presentation of the Nephrology Quiz and Questionnaire (NQQ) has become an annual
      "tradition" at the meetings of the American Society of Nephrology. It is a very
      popular session judged by consistently large attendance. Members of the audience
      test their knowledge and judgment on a series of case-oriented questions prepared
      and discussed by experts. They can also compare their answers in real time, using
      audience response devices, to those of program directors of nephrology training
      programs in the United States, acquired through an Internet-based questionnaire.
      As in the past, the topics covered were transplantation, fluid and electrolyte
      disorders, end-stage renal disease and dialysis, and glomerular disorders. Two
      challenging cases representing each of these categories along with single best
      answer questions were prepared by a panel of experts (Drs. Hricik, Palmer,
      Bargman, and Fervenza, respectively). The "correct" and "incorrect" answers then
      were briefly discussed, after the audience responses and the results of the
      questionnaire were displayed. The 2010 version of the NQQ was exceptionally
      challenging, and the audience, for the first time, gained a better overall
      correct answer score than the program directors, but the margin was small. In
      this issue we present the transplantation and fluid and electrolyte cases; the
      remaining end-stage renal disease and dialysis, and glomerular disorder cases
      will be presented next month. These articles try to recapitulate the session and
      reproduce its educational value for a larger audience--the readers of the
      Clinical Journal of the American Society of Nephrology. Have fun.

PMID- 21896835
TI  - Delayed urethral obstruction after uterine torsion in a pregnant dog.
AB  - A 4 yr old pregnant female shih tzu was presented with abdominal discomfort and
      bloody vulvar discharge. The nongravid uterine horn was reflected caudally over
      the trigone, obstructing urine outflow. A cesarian section and ovariohysterectomy
      were performed. Postoperatively, the hematuria and pollakiuria resolved.
      Seventeen days later, the pelvic urethra was completely obstructed by a soft
      tissue mass that was identified by rectal palpation, blocked catheterization
      attempts, contrast radiography, ultrasonography, and surgery. Management included
      temporary cystostomy tube and definitive prepubic urethrostomy. Histologic
      diagnosis was severe, multifocal, necrosuppurative urethritis with fibroplasia,
      fibrosis, and cellulitis, apparently secondary to ischemia. Delayed urethral
      obstruction is a potential complication of canine uterine torsion.

PMID- 21896836
TI  - Multifocal oligodendroglioma in three dogs.
AB  - This report describes the clinical, histopathologic, and imaging findings of
      multifocal oligodendrogliomas from three canine patients. Clinical history varied
      but included seizure activity and behavior changes. Neurologic examination
      abnormalities included ataxia, proprioceptive deficits, cranial nerve deficits,
      and changes in mentation. MRI in one patient revealed multifocal brain lesions;
      however, the MRI was normal in another one of the patients. Histopathologic
      evaluation identified multifocal neoplastic infiltrates in all three patients
      involving the cerebral cortex, brainstem, and spinal cord, with leptomeningeal
      extension in two of the three patients. All three patients were euthanized due to
      progression of their neurologic condition and/or complications due to aspiration
      pneumonia. Oligodendrogliomas should be considered a differential diagnosis for
      patients with multifocal brain disease.

PMID- 21896829
TI  - Cardiovascular disease among hispanics and non-hispanics in the chronic renal
      insufficiency cohort (CRIC) study.
AB  - BACKGROUND AND OBJECTIVES: Hispanics are the largest minority group in the United
      States. The leading cause of death in patients with chronic kidney disease (CKD)
      is cardiovascular disease (CVD), yet little is known about its prevalence among
      Hispanics with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted
      cross-sectional analyses of prevalent self-reported clinical and subclinical
      measures of CVD among 497 Hispanics, 1638 non-Hispanic Caucasians, and 1650 non
      Hispanic African Americans, aged 21 to 74 years, with mild-to-moderate CKD at
      enrollment in the Chronic Renal Insufficiency Cohort (CRIC) and Hispanic CRIC
      (HCRIC) studies. Measures of subclinical CVD included left ventricular
      hypertrophy (LVH), coronary artery calcification (CAC), and ankle-brachial index.
      RESULTS: Self-reported coronary heart disease (CHD) was lower in Hispanics
      compared with non-Hispanic Caucasians (18% versus 23%, P = 0.02). Compared with
      non-Hispanic Caucasians, Hispanics had a lower prevalence of CAC >100 (41% versus
      34%, P = 0.03) and CAC >400 (26% versus 19%, P = 0.02). However, after adjusting
      for sociodemographic factors, these differences were no longer significant. In
      adjusted analyses, Hispanics had a higher odds of LVH compared with non-Hispanic
      Caucasians (odds ratio 1.97, 95% confidence interval, 1.22 to 3.17, P = 0.005),
      and a higher odds of CAC >400 compared with non-Hispanic African Americans (odds
      ratio, 2.49, 95% confidence interval, 1.11 to 5.58, P = 0.03). Hispanic ethnicity
      was not independently associated with any other CVD measures. CONCLUSIONS:
      Prevalent LVH was more common among Hispanics than non-Hispanic Caucasians, and
      elevated CAC score was more common among Hispanics than non-Hispanic African
      Americans. Understanding reasons for these racial/ethnic differences and their
      association with long-term clinical outcomes is needed.

PMID- 21896837
TI  - Development of new canine and feline preventive healthcare guidelines designed to
      improve pet health.
AB  - The American Veterinary Medical Association (AVMA) and American Animal Hospital
      Association (AAHA) have jointly introduced the first Canine and Feline Preventive
      Healthcare Guidelines. These consensus statements provide veterinarians with a
      new resource for improving patient care by emphasizing the value and scope of
      regular pet examinations. The two guidelines provide complete recommendations for
      comprehensive preventive healthcare programs, published as accessible, single
      page documents. The guidelines are based on the subjective-objective-assessment
      plan (SOAP) methodology of case management, a proven approach traditionally used
      with sick or injured patients. This logical and disciplined process is equally
      applicable to healthy patients and is designed to consistently deliver optimal
      patient care. The guidelines recommend visits for health examinations on at least
      an annual basis, recognizing that for many pets, more frequent visits may be
      appropriate, depending on the individual needs of the patient. The guidelines
      also provide detailed diagnostic, therapeutic, prevention, and follow up plans,
      to be accompanied by appropriate documentation. The inclusive content and concise
      format of the guidelines are designed to maximize their practical value and make
      them easy to implement.

PMID- 21896838
TI  - Changes in vision- and health-related quality of life in patients with diabetic
      macular edema treated with pegaptanib sodium or sham.
AB  - PURPOSE: To compare vision function and self-reported quality of life (QoL) in
      patients with diabetic macular edema (DME) treated with intravitreous pegaptanib
      0.3 mg or sham injection. METHODS: This randomized (1:1), controlled, multicenter
      trial included subjects with DME (center point thickness on OCT, >= 250 MUm) and
      visual acuity (VA) <= 65 letters and >= 35 letters. In year 1, pegaptanib or sham
      was administered every 6 weeks with focal/grid photocoagulation at investigator
      discretion after week 18. Subjects received injections as often as every 6 weeks
      per pre-specified criteria in year 2. Primary efficacy endpoint: proportion
      gaining >=10 letters of VA from baseline to week 54. Change in QoL from baseline
      to weeks 54 and 102 was assessed with the 25-item National Eye Institute-Visual
      Function Questionnaire (NEI-VFQ 25) and the EQ-5D. RESULTS: One hundred thirty
      three pegaptanib- and 127 sham-treated subjects were in the year 1 intent-to
      treat population. From baseline to week 54, >= 10 letter gains seen in 49 (36.8%)
      pegaptanib- and 25 (19.7%) sham-treated subjects (odds ratio [95% CI]: 2.38 [1.32
      4.30]; P = 0.0047). At 2 years, the VA trend favored pegaptanib. The NEI-VFQ 25
      domains of Near Vision, Distance Vision, and Social Functioning (week 54) and
      Distance Vision, Social Functioning, Mental Health, and Composite Score (week
      102) demonstrated clinically meaningful (>5-point between-group difference) and
      statistically significant (P < 0.05) benefits favoring pegaptanib. No significant
      difference in the mean change in generic EQ-5D-weighted utility scores was seen.
      CONCLUSIONS: The VA improvement from pegaptanib treatment versus sham is
      reflected by improved vision-related QoL as reported by the DME patient
      (ClinicalTrials.gov number, NCT00605280).

PMID- 21896840
TI  - Light-induced trigeminal sensitization without central visual pathways: another
      mechanism for photophobia.
AB  - PURPOSE: The authors investigated whether trigeminal sensitization occurs in
      response to bright light with the retina disconnected from the rest of the
      central nervous system by optic nerve section. METHODS: In urethane-anesthetized
      rats, trigeminal reflex blinks were evoked with air puff stimuli directed at the
      cornea in darkness and at three different light intensities. After normative data
      were collected, the optic nerve was lesioned and the rats were retested. In an
      alert rat, reflex blinks were evoked by stimulation of the supraorbital branch of
      the trigeminal nerve in the dark and in the light. RESULTS: A 9.1 * 10(3)
      MUW/cm(2) and a 15.1 * 10(3) MUW/cm(2) light significantly enhanced the magnitude
      of reflex blinks relative to blinks evoked by the same trigeminal stimulus when
      the rats were in the dark. In addition, rats exhibited a significant increase in
      spontaneous blinking in the light relative to the blink rate in darkness. After
      lesioning of the optic nerve, the 15.1 * 10(3) MUW/cm(2) light still
      significantly increased the magnitude of trigeminal reflex blinks. CONCLUSIONS:
      Bright lights increase trigeminal reflex blink amplitude and the rate of
      spontaneous blinking in rodents. Light can modify trigeminal activity without
      involving the central visual system.

PMID- 21896839
TI  - Bicarbonate, NBCe1, NHE, and carbonic anhydrase activity enhance lactate-H+
      transport in bovine corneal endothelium.
AB  - PURPOSE: To identify and localize the monocarboxylate transporters (MCTs)
      expressed in bovine corneal endothelial cells (BCEC) and to test the hypothesis
      that buffering contributed by HCO(3)(-), sodium bicarbonate cotransporter
      (NBCe1), sodium hydrogen exchanger (NHE), and carbonic anhydrase (CA) activity
      facilitates lactate flux. METHODS: MCT1-4 expression was screened by RT-PCR,
      Western blot analysis, and immunofluorescence. Endogenous lactate efflux and/or
      pH(i) were measured in BCEC in HCO(3)(-)-free or HCO(3)(-)-rich Ringer, with and
      without niflumic acid (MCT inhibitor), acetazolamide (ACTZ, a CA inhibitor), 5-(N
      Ethyl-N-isopropyl)amiloride (EIPA) (Na(+)/H(+) exchange blocker), disodium 4,4'
      diisothiocyanatostilbene-2,2'-disulfonate (DIDS; anion transport inhibitor), or
      with NBCe1-specific small interfering (si) RNA-treated cells. RESULTS: MCT1, 2,
      and 4 are expressed in BCEC. MCT1 was localized to the lateral membrane, MCT2 was
      lateral and apical, while MCT4 was apical. pH(i) measurements showed significant
      lactate-induced cell acidification (LIA) in response to 20-second pulses of
      lactate. Incubation with niflumic acid significantly reduced the rate of pHi
      change (dpH(i)/dt) and lactate-induced cell acidification. EIPA inhibited
      alkalinization after lactate removal. Lactate-dependent proton flux was
      significantly greater in the presence of HCO(3)(-) but was reduced by ACTZ.
      Efflux of endogenously produced lactate was significantly faster in the presence
      of HCO(3)(-), was greater on the apical surface, was reduced on the apical side
      by ACTZ, as well as on the apical and basolateral side by NBCe1-specific siRNA,
      DIDS, or EIPA. CONCLUSIONS: MCT1, 2, and 4 are expressed in BCEC on both the
      apical and basolateral membrane (BL) surfaces consistent with niflumic acid
      sensitive lactate-H(+) transport. Lactate dependent proton flux can activate
      Na(+)/H(+) exchange and be facilitated by maximizing intracellular buffering
      capacity through the presence of HCO(3)(-), HCO(3)(-) transport, NHE and CA
      activity.

PMID- 21896841
TI  - Fate of corneal epithelial cells separated from limbus in vivo.
AB  - PURPOSE: To characterize corneal epithelial cells separated from limbus in vivo
      by transplantation of a stainless steel ring with or without creating a defect
      inside the ring. METHODS: A stainless steel ring (diameter, 8 mm; width, 300 MUm;
      depth, 250 MUm) was transplanted into rabbit corneal stroma using 10-0 nylon
      interrupted suture after cutting to a 250 MUm depth by corneal vacuum trephine
      (diameter, 8.0 mm). Epithelial cells were removed inside the ring, and re
      epithelization was evaluated after 1 week. Hematoxylin staining and
      immunostaining against p63, Ki67, and cytokeratin 3 were performed for phenotypic
      analysis of corneal epithelia. A corneal epithelial defect was centrally created
      inside the ring (4, 5, and 6 mm diameter) after transplantation. When re
      epithelization was achieved, a central epithelial defect was continuously created
      until cells were exhausted within the ring. The number of created defects was
      also analyzed to assess the potential of re-epithelialization. RESULTS: Ring
      transplanted corneal stroma showed few signs of inflammation, and when epithelium
      was totally removed from inside the ring, complete epithelial defects were
      persistent for >= 1 month. Corneal sensation was significantly decreased in
      corneas with the ring (P < 0.05). Immunostaining demonstrated similar expression
      patterns for p63, Ki67, and cytokeratin3 as the controls. When rings were
      transplanted into the intact cornea, inside epithelia prevented epithelial
      defects in vivo for <= 6 months. CONCLUSIONS: Transient-amplifying cells might
      maintain homeostasis for >1 month when separated from their limbus in vivo. This
      model will be useful for future stem cell research or wound healing models.

PMID- 21896842
TI  - Effects of shear stress on the gene expressions of endothelial nitric oxide
      synthase, endothelin-1, and thrombomodulin in human retinal microvascular
      endothelial cells.
AB  - PURPOSE: Physiological shear stress is higher in the retinal microcirculatory
      network than in other organs. The effects of laminar shear stress on gene
      expression in human retinal microvascular endothelial cells (HRMECs) was
      investigated. METHODS: Cultured HRMECs on glass plates were exposed to a laminar
      shear stress of 0, 1.5, 6, 15, 30, 60, or 100 dyne/cm(2) for 24 hours and to 60
      dyne/cm(2) for 0, 1, 3, 6, 12, 24, or 48 hours. The mRNA expressions of
      endothelial nitric oxide synthase (eNOS), endothelin-1 (ET-1), and thrombomodulin
      (TM) in the HRMECs were evaluated using real-time reverse transcription
      polymerase chain reaction. RESULTS: The HRMECs elongated and aligned parallel
      with the flow direction based on the shear stress and exposure times. The
      expression of eNOS mRNA gradually increased and became saturated at 60
      dyne/cm(2); ET-1 mRNA expression increased at 1.5 dyne/cm(2) but decreased below
      that of the static control at shear stresses of 30 dyne/cm(2) or more. TM mRNA
      expression in response to shear stress increased linearly from 0 to 100
      dyne/cm(2). A shear stress of 60 dyne/cm(2) for 6 hours or more promoted eNOS and
      TM mRNA expression but suppressed ET-1 mRNA expression in HRMECs. CONCLUSIONS:
      Long-term exposure to a physiological shear stress in the retinal arterioles up
      regulated eNOS and TM mRNA expressions and downregulated ET-1 mRNA expression in
      HRMECs. These results suggest that shear stress may be associated with the
      vasoregulatory and antithrombotic properties of retinal vessels under
      physiological conditions present during retinal circulation.

PMID- 21896843
TI  - Evaluation of an algorithm for detecting visual field defects due to chiasmal and
      postchiasmal lesions: the neurological hemifield test.
AB  - PURPOSE: To develop an automated neurologic hemifield test (NHT) to detect visual
      field loss caused by chiasmal or postchiasmal lesions. METHODS: Visual field
      locations from 24-2 pattern automated visual fields were grouped into two
      symmetric regions with 16 points on either side of the vertical meridian. A
      scoring system similar to the Glaucoma Hemifield Test (GHT) was used to calculate
      point scores using the pattern deviation values from the right and left regions.
      The cross-vertical difference in the sum of these values was the NHT score. The
      NHT was evaluated using visual fields from subjects with known neurologic
      disease, subjects with glaucoma, and glaucoma suspects (92 pairs of eyes each).
      The NHT score was calculated for each eye. Four masked reviewers scored all pairs
      of visual fields with regard to the likelihood of neurologic and glaucomatous
      optic neuropathy. Both NHT score and expert field ratings were compared with
      clinical diagnosis by receiver operating characteristic (ROC) analysis. RESULTS:
      The NHT effectively discriminated neurologic fields from those of glaucoma
      patients and glaucoma suspects (area under the ROC curve [AUC] = 0.90; 95%
      confidence interval [CI], 0.86-0.94). The NHT score correlated well with
      clinician grading (Pearson correlation estimates, 0.74-0.78). Even when field
      defects were subtle, the NHT had some ability to discriminate neurologic from
      nonneurologic fields (AUC 0.68; 95% CI, 0.56-0.79). CONCLUSIONS: The NHT
      distinguished neurologic field defects from those of glaucoma and glaucoma
      suspects, rivaling the performance of subspecialist clinicians. Its
      implementation may help identify unsuspected neurologic disease.

PMID- 21896844
TI  - Aberrant kinetics of bone marrow-derived endothelial progenitor cells in the
      murine oxygen-induced retinopathy model.
AB  - PURPOSE: Retinopathy of prematurity (ROP) causes serious blindness because of the
      vasculopathy that results from the abnormal oxygen dynamics. However, the
      systemic kinetics of bone marrow-derived endothelial progenitor cells (BM-derived
      EPCs) during the "postnatal vasculogenesis " of ROP has yet to be elucidated.
      Thus, the authors investigated the kinetics of BM-derived EPCs using a murine
      oxygen-induced retinopathy (OIR) model. METHODS: OIR was induced in C57BL/6J mice
      by continual aeration with 75% oxygen from postnatal day (P) 7 to P12 that
      afterward returned to normal room air. RESULTS: The frequency of circulating EPCs
      (Sca-1(+)/c-Kit(+) cells in blood) in an OIR model estimated by FACS decreased
      immediately after the hyperoxic phase (P12) and then increased at the hypoxic
      phase (P17) compared with control. Further, EPC colony-forming assay of BM-Lin(
      )/Sca-1(+) (BM-LS) cells exhibited a conversion from the predominant primitive
      EPC colony production at P12 to the definitive EPC colony at P17. In the OIR
      retinas of BM-transplanted mice with BM-LS cells of EGFP transgenic mice, there
      was less incorporation of GFP(+) cells into vascular structures at P12, whereas
      there was a drastic recruitment into the "tufts " and for the intact vasculature
      at P17. Moreover, the definitive EPC colony cells intravitreally injected into
      OIR significantly abrogated pathologic versus primitive vascular growth.
      CONCLUSIONS: Taken together, these findings propose that the deviation of
      functional bioactivities of BM-derived EPCs contributing to intact vascular
      development under the abnormal oxygen dynamics may provide important mechanistic
      insight into pathologic vascular development in ROP.

PMID- 21896845
TI  - In vivo serial imaging of regenerating corneal nerves after surgical transection
      in transgenic thy1-YFP mice.
AB  - PURPOSE: To determine the effect of lamellar transection surgery on the nerve
      fiber density (NFD) and pattern of nerve regeneration in the cornea of thy1-YFP
      transgenic mice. METHODS: Wide-field stereo fluorescence microscopy was used to
      obtain serial images of nerves in live thy1-YFP mice, which express a fluorescent
      protein in their axons. NFD (mm/mm(2)) was calculated from maximum intensity
      projection images as the total length of fibers within the area of the contour in
      which nerves were traced. Whole-mount confocal microscopy was performed to
      analyze the arrangement of nerves and the types of regenerating fibers. RESULTS:
      NFD in normal corneas was 35.3 +/- 1.8 mm/mm(2). Stereo fluorescence microscopy
      revealed the presence of a subbasal hairpin nerve layer and an intrastromal nerve
      trunk layer. After surgery, regenerative sprouting was observed from transected
      distal ends of intrastromal nerve trunks. NFD also increased, with this increase
      being maximal between 4 and 6 weeks after surgery. NFD approximated baseline
      values at 6 weeks and did not change any further at 8 weeks. Regenerated nerves
      did not readopt the normal corneal nerve arrangement. A dense interlacing network
      of regenerated nerves was present in the corneal bed. Branches from this network
      traversed the flap to innervate the epithelium. Immunofluorescence staining
      revealed that regenerating fronds contained peptidergic nociceptive fibers
      (positive for calcitonin gene-related peptide and substance P) and myelinated non
      nociceptive fibers (positive for neurofilament 200). CONCLUSIONS: Although
      corneal NFD recovers to normal levels by 8 weeks after nerve transection, the
      arrangement of regenerated nerves is abnormal.

PMID- 21896846
TI  - Cytoskeletal dependence of adenosine triphosphate release by human trabecular
      meshwork cells.
AB  - PURPOSE: To test whether adenosine triphosphate (ATP) release links cytoskeletal
      remodeling with release of matrix metalloproteinases (MMPs), regulators of
      outflow facility and intraocular pressure. METHODS: ATP release was measured by
      luciferin-luciferase. Ecto-ATPases from transformed human trabecular meshwork
      (TM) cells (TM5) and explant-derived TM cells were identified by RT-PCR. Actin
      was visualized by phalloidin staining. Cell viability was assayed by lactate
      dehydrogenase and thiazolyl blue tetrazolium bromide methods and propidium iodide
      exclusion, gene expression by real-time PCR, and MMP release by zymography. Cell
      volume was monitored by electronic cell sorting. RESULTS: Hypotonicity (50%) and
      mechanical stretch increased ATP release with similar pharmacologic profiles. TM
      cells expressed ecto-ATPases E-NPP1-3, E-NTPD2, E-NTPD8, and CD73. Prolonged
      dexamethasone (DEX) exposure (>= 2 weeks), but not brief exposure (3 days),
      increased cross-linked actin networks and reduced swelling-triggered ATP release.
      Cytochalasin D (CCD) exerted opposite effects. Neither DEX nor CCD altered the
      cell viability, gene expression, or pharmacologic profile of ATP-release
      pathways. DEX accelerated, and CCD slowed, the regulatory volume decrease after
      hypotonic exposure. Activating A(1) adenosine receptors (A(1)ARs) increased total
      MMP-2 and MMP-9 release. DEX reduced total A(1)AR-triggered MMP release, and CCD
      increased the active form of MMP-2 release. The A(1)AR agonist CHA and the A(1)AR
      antagonist DPCPX partially reversed the effects of DEX and CCD, respectively.
      CONCLUSIONS: Cytoskeletal restructuring modulated swelling-activated ATP release,
      in part by changing the duration of cell swelling after hypotonic challenge.
      Modifying ATP release is expected to modulate MMP secretion by altering ecto
      enzymatic delivery of adenosine to A(1)ARs, linking cytoskeletal remodeling and
      MMP-mediated modulation of outflow facility.

PMID- 21896848
TI  - Correct calculation circle location of optical coherence tomography in measuring
      retinal nerve fiber layer thickness in eyes with myopic tilted discs.
AB  - PURPOSE. Retinal nerve fiber layer (RNFL) thickness measured by optical coherence
      tomography (OCT) can be unreliable in the presence of a myopic tilted disc. The
      purpose of this study was to investigate the influence of the calculation circle
      location of spectral domain (SD)-OCT when measuring RNFL thickness in healthy
      subjects with myopic tilted disc. METHODS. Sixty-nine eyes with myopic tilted
      disc and no other ocular abnormalities were analyzed. In all eyes, RNFL thickness
      was measured twice: first, along a calculation circle determined by a built-in
      algorithm (referred to as circle 1) and then along a manually positioned
      calculation circle based on the contours of the neural canal opening (NCO)
      (referred to as circle 2). The mean number of clock hours below normal at the 5%
      level and the proportion of eyes with abnormally thin clock hours at the 5% level
      were compared between the two methods: RESULTS. The mean number of clock hours
      below normal at the 5% level was significantly lower in circle 2 (0.84 +/- 1.31)
      than in circle 1 (1.42 +/- 1.43; P < 0.05). The proportion of eyes with
      abnormally thin clock hours at the 5% level was significantly lower (P < 0.001)
      in circle 2 (42%) than in circle 1 (69.9%). CONCLUSIONS. In subjects with myopic
      tilted disc, RNFL thickness measurements along the calculation circle based on
      the contours of the NCO seem to be more comparable to the normative database of
      the SD-OCT than does the automatically determined scan position.

PMID- 21896847
TI  - Identification of a novel locus for autosomal dominant primary open angle
      glaucoma on 4q35.1-q35.2.
AB  - PURPOSE: Primary open angle glaucoma is the most prevalent type of glaucoma and
      the leading cause of irreversible blindness worldwide. The genetic basis is
      poorly understood. Of 14 loci associated with this disease, only two genes have
      been identified, accounting for approximately 4% of cases. The authors
      investigated the genetic cause of primary open angle glaucoma in a large four
      generation family with an apparent autosomal dominant mode of inheritance.
      METHODS: Twenty-three family members underwent comprehensive phenotyping by a
      single ophthalmologist, and the MYOC gene was sequenced in all affected family
      members for whom DNA was available. Parametric genomewide linkage analysis was
      performed on 10 affected family members and one unaffected family member. Within
      the critical region, mutation analysis of candidate genes LRP2BP, CYP4V2, and
      UFSP2 was carried out by direct sequencing. RESULTS: No mutations were identified
      in MYOC. Genomewide linkage analysis generated one significant LOD score of 3.1
      (maximum affected-only LOD score of 2.8) centered on chromosome 4 at 4q35.1
      q35.2, a critical region that does not contain any of the previously reported
      primary open angle glaucoma loci. A 1.866-Mb (7.2 cM) region was identified
      containing 17 known or hypothetical genes. No mutations were identified in the
      candidate genes LRPB2BP, CYP4V2, and UFSP2. CONCLUSIONS: This study identifies a
      new primary open angle glaucoma locus, GLC1Q, in a region on chromosome 4 not
      previously associated with glaucoma.

PMID- 21896849
TI  - Uveal melanoma cell lines contain stem-like cells that self-renew, produce
      differentiated progeny, and survive chemotherapy.
AB  - PURPOSE: Uveal melanoma (UM) cells in high-metastatic risk tumors have an
      undifferentiated molecular signature indicative of a more primitive cellular
      phenotype. Given mounting evidence for the existence of cancer stem cells (CSC),
      the authors investigated whether UM cell lines retain a population of self
      renewing tumorigenic cells. METHODS: Single-cell cloning and spheroid culture
      studies were used to study the presence of a CSC-like population in two cell
      lines derived from the primary tumor (Mel270) and metastatic liver lesion
      (Omm2.5) of the same patient. RESULTS: Mel270 and Omm2.5 cells exhibited distinct
      clonal morphologies in adherent culture akin to holoclones, meroclones, and
      paraclones. Holoclones were large colonies of tightly packed small cells, which
      could be serially passaged (> 10 generations) to produce colonies of all three
      types; paraclones were small colonies of flattened cells that could be passaged
      for only one or two generations to produce further paraclones. Mel270 and Omm2.5
      cells surviving cisplatin treatment produced significantly more holoclones than
      untreated cells (P < 0.05), suggesting enrichment for this CSC-like
      subpopulation. Mel270 and Omm2.5 cells also formed melanomaspheres (MS) when
      grown at clonal density in nonadherent culture. MS possessed self-renewal
      capacity to generate further MS and when replated to adherent culture yielded
      colonies of all three types. Mel270 and Omm2.5 holoclones and MS also
      demonstrated antigenic heterogeneity expressing markers associated with both a
      primitive migratory neural crest phenotype, and a more differentiated phenotype.
      CONCLUSIONS: These data suggest the presence in UM cell lines, of a CSC-like
      subpopulation with enhanced self-renewal and proliferative capabilities that
      could more appropriately model therapeutic efficacy.

PMID- 21896850
TI  - The ringlike structure of macular pigment in age-related maculopathy: results
      from the Muenster Aging and Retina Study (MARS).
AB  - PURPOSE: The role of macular pigment (MP) in age-related maculopathy (ARM) is
      still not clearly understood. Recent studies have reported on variations in the
      spatial distribution of MP optical density (MPOD) including a secondary peak
      ("ring") in the slope of the MPOD profile. The authors investigated in a cross
      sectional manner the presence of ringlike structures, their determinants, and
      their relationship with ARM. METHODS: In all, 369 participants of the Muenster
      Aging and Retina Study were examined using dual-wavelength analysis of
      autofluorescence images. ARM was graded using digital fundus photographs
      according to the International Classification System. RESULTS: A ringlike
      structure was observed in 73 (19.8%) study participants. The MP maximum of the
      ring was located on average at 0.85 degrees  and the minimum at 0.48 degrees 
      from the center of the fovea. Their concordance between pairs of eyes was highly
      significant. MPOD measured at eccentricities of 0 degrees , 0.25 degrees , and
      0.5 degrees  from the fovea was significantly lower in eyes with ringlike
      structure, whereas it was significantly higher at 1.0 degrees  and 2.0 degrees 
      than that in eyes without the ring. Ringlike structures were significantly more
      common in females and never smokers and were found significantly less often in
      eyes with ARM than in healthy eyes, even after adjustment for influential factors
      (adjusted odds ratio, 0.347; 95% confidence interval, 0.196-0.617). CONCLUSIONS:
      Ringlike structures in the MP spatial profile are fairly common, show a high
      degree of bilaterality, and appeared inversely related with ARM.

PMID- 21896852
TI  - Early-stage retinal melatonin synthesis impairment in streptozotocin-induced
      diabetic wistar rats.
AB  - PURPOSE: Retinal melatonin synthesis occurs in the photoreceptor layer in a
      circadian manner, controlling several physiologic rhythmic phenomena, besides
      being the most powerful natural free radical scavenger. The purpose of the
      present work was to evaluate the diurnal profile of retinal melatonin content and
      the regulation of its synthesis in the retina of streptozotocin-induced diabetic
      rats. METHODS: Diabetes was induced in male Wistar rats (12 hour-12 hour
      light/dark cycle) with streptozotocin. Control, diabetic, and insulin-treated
      diabetic animals were killed every 3 hours throughout the light-dark cycle.
      Retinal melatonin content was measured by high-performance liquid chromatography,
      arylalkylamine N-acetyltransferase (AANAT) activity was analyzed by radiometric
      assay, Bmal1 gene expression was determined by qPCR, and cyclic adenosine
      monophosphate (cAMP) content was assessed by ELISA. RESULTS: Control animals
      showed a clear retinal melatonin and AANAT activity daily rhythm, with high
      levels in the dark. Diabetic rats had both parameters reduced, and the impairment
      was prevented by immediate insulin treatment. In addition, the Bmal1 expression
      profile was lost in the diabetic group, and the retinal cAMP level was reduced 6
      hours after lights on and 3 hours after lights off. CONCLUSIONS: The present work
      shows a melatonin synthesis reduction in diabetic rats retinas associated with a
      reduction in AANAT activity that was prevented by insulin treatment. The Bmal1
      flattened gene expression and the cAMP reduction seem to be responsible for the
      AANAT activity decrease in diabetic animals. The melatonin synthesis reduction
      observed in the pineal gland of diabetic rats is also observed in a local
      melatonin tissue synthesizer, the retina.

PMID- 21896851
TI  - Shape analysis of the peripapillary RPE layer in papilledema and ischemic optic
      neuropathy.
AB  - PURPOSE: Geometric morphometrics (GM) was used to analyze the shape of the
      peripapillary retinal pigment epithelium-Bruch's membrane (RPE/BM) layer imaged
      on the SD-OCT 5-line raster in normal subjects and in patients with papilledema
      and ischemic optic neuropathy. METHODS: Three groups of subjects were compared:
      30 normals, 20 with anterior ischemic optic neuropathy (AION), and 25 with
      papilledema and intracranial hypertension. Twenty equidistant semilandmarks were
      digitized on OCT images of the RPE/BM layer spanning 2500 MUm on each side of the
      neural canal opening (NCO). The data were analyzed using standard GM techniques,
      including a generalized least-squares Procrustes superimposition, principal
      component analysis, thin-plate spline (to visualize deformations), and
      permutation statistical analysis to evaluate differences in shape variables.
      RESULTS: The RPE/BM layer in normals and AION have a characteristic V shape
      pointing away from the vitreous; the RPE/BM layer in papilledema has an inverted
      U shape, skewed nasally inward toward the vitreous. The differences were
      statistically significant. There was no significant difference in shapes between
      normals and AION. Pre- and posttreatment OCTs, in select cases of papilledema,
      showed that the inverted U-shaped RPE/BM moved posteriorly into a normal V shape
      as the papilledema resolved with weight loss or shunting. CONCLUSIONS: The shape
      difference in papilledema, absent in AION, cannot be explained by disc edema
      alone. The difference is a consequence of both the translaminar pressure gradient
      and the material properties of the peripapillary sclera. GM offers a novel way of
      statistically assessing shape differences of the peripapillary optic nerve head.

PMID- 21896853
TI  - Induction of retinal pigment epithelial cells from monkey iPS cells.
AB  - PURPOSE: The induced pluripotent stem (iPS) cell is expected to be a powerful
      tool for research and development in regenerative medicine. Previously, the
      authors reported that human iPS cells differentiated into retinal cells,
      including photoreceptors and retinal pigment epithelial cells. In this study,
      they produced iPS cell lines from monkeys to investigate their ability to
      differentiate into retinal cells. METHODS: To generate iPS cells, the fibroblasts
      derived from cynomolgus monkey abdominal skin were infected with retroviruses
      carrying Oct3/4, Sox2, Klf4, and c-Myc genes and then were cultured on STO feeder
      cells. Next, the established iPS cells were cultured with the conditioned medium
      of PA6 cells to induce RPE cells. The properties of the differentiated RPE cells
      were analyzed. RESULTS: Approximately 1 month after viral infection, some
      epithelial-like colonies appeared among the fibroblasts. These colonies were
      morphologically similar to the cynomolgus embryonic stem (ES) cell and expressed
      ES cell-specific markers. By producing teratomas in SCID mice, these cells were
      confirmed to have the ability to differentiate into three germ layers. In
      addition, the RPE cells induced from the monkey iPS cells had characteristic
      polygonal shapes and pigments. These cells expressed RPE cell-specific markers
      such as RPE65, CRALBP, Bestrophin 1, and MERTK and exhibited phagocytotic
      function in vitro. CONCLUSIONS: The RPE cells derived from monkey skin with iPS
      cell technology can be used for autologous or allogeneic transplantation to test
      the possibility of immune rejection and to evaluate their function in vivo with
      the same techniques that will be used in clinical trials.

PMID- 21896854
TI  - Ultrastructural localization and expression of TRPM1 in the human retina.
AB  - PURPOSE: Transient receptor potential subfamily melastatin (TRPM)1 cation
      channels of retinal ON-bipolar cells are modulated via a mGluR6 (GMR6) signaling
      cascade. While light-microscopy shows these channels are located on the tips of
      ON-bipolar cells dendrites, near rod and cone synaptic ribbons, TRPM1
      localization at the electron-microscope level is currently not described. The
      authors report here the ultrastructural localization of TRPM1 in the human
      retina. METHODS: TRPM1 was localized in postmortem human retinas by
      immunohistochemistry at both the light and electron microscope levels.
      Additionally, TRPM1 expression was studied using in situ hybridization, laser
      dissection microscopy, and PCR techniques. RESULTS: TRPM1-immunoreactivity was
      located on the dendrites and soma of ON-bipolar cells at the light microscope
      level. At the electron microscope level TRPM1-immunoreactivity was located on the
      tips of ON-bipolar cell dendrites that were invaginating cone pedicles and rod
      spherules. In addition, TRPM1-immunoreactivity was occasionally found on the rod
      spherules ribbons, suggesting that at least a proportion of rods may also express
      TRPM1. In situ hybridization showed TRPM1 encoding RNA in inner nuclear layer
      somata and in some photoreceptors. The presence of TRPM1-RNA in photoreceptors
      was confirmed by PCR in pure photoreceptor material obtained with a laser
      dissection microscope. CONCLUSIONS: In the human retina TRPM1 is expressed on ON
      bipolar cell dendrites that invaginate photoreceptor terminals. TRPM1 is also
      expressed on the synaptic ribbons of a subclass of rods, suggesting a dual
      function for TRPM1 in the ON-pathway.

PMID- 21896856
TI  - The time course of visual field recovery and changes of retinal ganglion cells
      after optic chiasmal decompression.
AB  - PURPOSE: To investigate the time course of visual field recovery and changes of
      retinal ganglion cells (RGCs) after chiasmal decompression using standard
      automated perimetry (SAP), optical coherence tomography (OCT), and photopic
      negative response (PhNR). METHODS: Nineteen patients undergoing chiasmal
      decompression surgery were prospectively assessed before and 1 and 3 months after
      surgery. The same examinations were conducted in nine patients at 6 months after
      surgery. Mean deviation and temporal visual field sensitivity (1/Lambert) of SAP,
      retinal nerve fiber layer (RNFL) thickness, and ganglion cell complex (GCC) area
      measured by OCT and PhNR/b-wave ratio were analyzed. Preoperative measurements
      were compared with those of 20 eyes of normal controls. Postoperative
      measurements were compared with preoperative data. The relationships among SAP,
      OCT, and PhNR measurements throughout the observation periods were evaluated by
      linear and logarithmic regressions. RESULTS: Before surgery, all parameters in
      patients were significantly worse than those in normal controls. After surgery,
      the visual field was significantly improved, but RNFL thickness and GCC area were
      significantly reduced for 3 months. The PhNR/b-wave ratio was also reduced, but
      not significantly. Six months after surgery, average RNFL thickness, GCC area,
      and PhNR/b-wave ratio showed significant improvements by 2.82%, 2.66%, and 8.72%,
      respectively, than those at 3 months. Visual fields were significantly correlated
      with RNFL thickness, GCC area, and PhNR/b-wave ratio. CONCLUSIONS: Visual field
      recovery and changes of RGCs after chiasmal decompression have similar aspects
      and are significantly correlated. However, prolonged retrograde degeneration
      progressed for some period, even after surgical decompression and visual field
      recovery preceded demonstrable retinal regeneration.

PMID- 21896855
TI  - The clinical phenotype of trachomatous trichiasis in Ethiopia: not all trichiasis
      is due to entropion.
AB  - PURPOSE: Trachomatous trichiasis (TT) is usually described as a cicatricial
      entropion of the upper lid; however, other forms of trichiasis have been
      reported. This variation in clinical phenotype is potentially important for
      treatment guidelines. Therefore, this study was conducted to investigate the
      range of disease type and severity encompassed by TT. METHODS: Individuals
      presenting with TT to surgical treatment campaigns were examined by a single
      ophthalmologist using the Detailed WHO Trachoma Grading System. Additional
      features were graded, including type of trichiatic lashes (metaplastic,
      misdirected, and entropic), lower lid trichiasis, entropion severity, and lid
      margin mucocutaneous junction (MCJ) position. RESULTS: Recruited were 2556
      individuals with previously unoperated TT in at least one eye (4310 eyes). The
      median number of lashes touching the eye was 2 (range, 0 [epilating]-133).
      Entropion was absent or mild in 2328 (54.0%) eyes, moderate in 1259 (29.2%) eyes,
      and severe in 723 (16.8%) eyes. Trichiatic lashes were predominantly metaplastic
      or misdirected (80.2%), rather than secondary to entropion; 4204 (97.7%) had
      anteroplacement of the MCJ; and lower lid trichiasis was present in 494 (11.5%).
      Entropion was more severe among those with a low BMI, those who were female,
      those aged less than 50 years, and those with moderate to severe conjunctival
      inflammation, central corneal opacity, and severe conjunctival scarring.
      CONCLUSIONS: Many patients with TT have minimal or no entropion. The trichiasis
      is frequently attributable to metaplastic or misdirected eyelashes. The results
      of tarsal rotation surgery in TT patients without manifest entropion should be
      investigated and potentially alternative treatment strategies evaluated.

PMID- 21896857
TI  - Test-retest, within-visit variability of Goldmann visual fields in retinitis
      pigmentosa.
AB  - PURPOSE: Reliable outcome measures are needed to estimate changes in peripheral
      vision during future treatment clinical trials for retinal degeneration patients.
      The authors examined the short-term variability of Goldmann visual field (GVF)
      results converted to retinal areas in retinitis pigmentosa (RP) subjects.
      METHODS: Two within-visit GVFs were obtained from one eye each of 37 RP subjects
      with visual acuity better than 20/400 by a single experienced operator using the
      V4e (n = 28) or III4e (n = 12) target, or both. Planimetric GVF measures were
      digitized and converted to retinal areas in square millimeters by a single
      independent user. The 95% coefficient of repeatability (CR.(95)) for percentage
      change in central retinal area was determined from the test-retest difference.
      RESULTS: There were no significant systematic trends toward either increase or
      decrease between the first and second GVF. For the III4e target, the CR.(95) was
      23.7% on average across all 12 subjects. For the V4e target, the CR.(95) was
      32.8% on average across all 28 subjects. However, 3 of 8 subjects with a
      geometric mean retinal area <10 mm(2) (~7 degrees  radius) for the V4e target
      exhibited unusually large variability (50%-100%), and the CR.(95) was 19.2% when
      these three subjects were excluded. Variability was not statistically
      significantly related to visual acuity, age, presence of cystoid macular edema,
      or subjects' stress or anxiety levels. CONCLUSIONS: Inherent test-retest
      variability (CR.(95)) of functional retinal areas derived from GVF results in a
      clinical RP population can be limited to <20% by using a single experienced
      operator, making the GVF the measure of choice for changes in peripheral vision.

PMID- 21896858
TI  - Association between depression and dry eye disease in an elderly population.
AB  - PURPOSE: A population-based cross-sectional study to investigate the association
      between depression and dry eye disease (DED) in a community-dwelling elderly
      population. METHODS: The subjects were 657 Korean elders >= 65 years of age
      randomly selected from an official household registration database in Yongin,
      Korea. DED symptoms were assessed using the six-item Dry Eye Questionnaire. DED
      signs were evaluated using the Schirmer test, fluorescein stain score, tear film
      break-up time (BUT). Depression was assessed using the Korean version of the
      Short Geriatric Depression Scale (SGDS-K). The association between DED and
      depression was evaluated using logistic linear analyses. RESULTS: The SGDS-K
      score correlated with the number of positive responses in the Dry Eye
      Questionnaire (r = 0.229, P < 0.001), but not with tear film break-up time (r =
      0.041, P = 0.139) or Schirmer test score (r = 0.048, P = 0.642). In the binary
      logistic regression model, female sex (P = 0.014), residence in urban areas (P <
      0.001), depression (P < 0.001), and Schirmer score of <= 5 mm (P = 0.035) were
      associated with the risk of DED. Depression was associated with the risk of DED
      (P < 0.001) in the patients with Schirmer score > 5 mm but not in those with
      Schirmer score <= 5 mm (P = 0.290). CONCLUSIONS: Depression was associated with
      DED symptoms in subjects with normal or mildly reduced tear production.

PMID- 21896859
TI  - Topical dexamethasone-cyclodextrin microparticle eye drops for diabetic macular
      edema.
AB  - PURPOSE: To test the safety and efficacy of topical 1.5% dexamethasone aqueous
      eye drops with cyclodextrin microparticles for diabetic macular edema (DME).
      METHODS: Nineteen eyes of 19 consecutive patients with DME were administered
      dexamethasone-cyclodextrin eye drops three or six times a day for 4 weeks and
      then observed for 4 weeks without treatment. Visual acuity, intraocular pressure,
      and spectral domain optical coherent tomography-measured central macular
      thickness recordings at weeks 0 (baseline), 4, and 8. These parameters were
      compared using Bonferroni-corrected paired t-tests. RESULTS: At weeks 0, 4, and
      8, logMAR visual acuity (mean +/- SD) was 0.52 +/- 0.41, 0.37 +/- 0.40 (P =
      0.0025 vs. baseline), and 0.45 +/- 0.41, respectively; central macular thickness
      (MUm) was 512 +/- 164, 399 +/- 154 (P = 0.0016 vs. baseline), and 488 +/- 172 (P
      = 0.0116 versus week 4), respectively; and intraocular pressure (mm Hg) was 15.2
      +/- 3.1, 17.4 +/- 4.2 (P = 0.0015 vs. baseline) and 15.8 +/- 4.0, respectively.
      At week 4, in 12 (63%) of 19 eyes, central macular thickness had decreased more
      than 10%, and the mean change was -20% (-65% to +10%). In 14 of 19 eyes (74%)
      visual acuity (logMAR) had improved more than 0.1 at week 4. No subjects showed
      severe adverse effects related to the eye drops. CONCLUSIONS: Based on this short
      pilot study, topical dexamethasone-cyclodextrin eye drops are well tolerated,
      decrease central macular thickness, and improve visual acuity in DME. The results
      encourage comparative studies between dexamethasone cyclodextrin microparticle
      eye drops and other treatments for DME. (http://www.umin.ac.jp/ctr number,
      UMIN000001790.).

PMID- 21896860
TI  - Association of genetic variation on chromosome 9p21 with polypoidal choroidal
      vasculopathy and neovascular age-related macular degeneration.
AB  - PURPOSE: Polypoidal choroidal vasculopathy (PCV) contains aneurismal morphologic
      and histopathologic feature and it is considered to be a possible distinct entity
      from neovascular age-related macular degeneration (AMD). In this study, the
      association of identified risk variants for intracranial aneurysm on chromosome
      9p21 with PCV and neovascular AMD in a Chinese Han population was investigated.
      METHODS: The authors genotyped rs1333040 and rs10757278 on 9p21 in 177 PCV
      patients, 131 neovascular AMD patients, and 182 controls using a genotyping
      method and direct DNA sequencing. Allele and genotypes frequencies in the PCV and
      neovascular AMD groups were compared with controls using a free open-source
      software and binary logistic regression analysis. RESULTS: Rs1333040 was not
      associated with PCV or neovascular AMD. Rs10757278 was significantly associated
      with PCV [risk allele: A, P (allelic) = 0.014; odds ratio = 1.44; 95% confidence
      interval, 1.08-1.94], but not associated with neovascular AMD. After adjusting
      for sex, age, smoking status, history of hypertension, type 2 diabetes, and
      coronary artery disease, the odds ratio for homozygous carriers of rs10757278-A
      was 2.10 (95% confidence interval, 1.14-3.85) for PCV. CONCLUSIONS: The
      rs10757278 on chromosome 9p21 is significantly associated with the risk of PCV
      but not with neovascular AMD in the Chinese Han population.

PMID- 21896861
TI  - Longitudinal changes of axial length and height are associated and concomitant in
      children.
AB  - PURPOSE: To examine the association between the longitudinal changes of axial
      length (AL) and height in Chinese children. METHODS: The study participants were
      recruited from the Guangzhou Twin Registry. AL and height were measured every
      year from 2006 to 2008. AL was measured using partial coherence laser
      interferometry. Height was measured with the participants standing without shoes.
      Bivariate correlation coefficients and a multivariate generalized regression
      model were used to calculate the association between the changes of AL and
      height. Data from the first-born twins were selected to present the results: The
      right eye was arbitrarily selected to represent AL of the specific individual.
      RESULTS: Mean annual increases of AL and height were 0.22 (SD, 0.17) mm and 3.93
      (SD, 3.02) cm, respectively. Correlations between AL and height were 0.47 (95%
      CI, 0.40-0.52) in 2006. The correlation between AL at 2006 and height at 2008 was
      0.44 (95% CI, 0.37-0.51); the correlation between AL at 2008 and height at 2006
      was 0.38 (95% CI, 0.32-0.45). These cross-trait cross-time correlation
      coefficients remained statistically significant after adjusting for age and sex.
      Plotting the changes of AL and height suggested that the changes of AL and height
      with age were concomitant; greater changes were observed in younger children.
      CONCLUSIONS: The association between AL and height in cross-sectional analysis
      and longitudinal changes may suggest common pathways for the development of eye
      size and body size in children.

PMID- 21896862
TI  - Corneal modulus and IOP measurements in canine eyes using Goldmann applanation
      tonometry and Tono-pen.
AB  - PURPOSE: To experimentally examine the effect of corneal modulus on Goldmann
      applanation tonometry (GAT) and Tono-pen (Tono-pen XL, Reichert, Inc., Depew, NY)
      measurements of intraocular pressure (IOP) in a canine eye model. METHODS: Twenty
      one canine globes were recovered from healthy animals. IOP was controlled at 10,
      15, 20, 30, and 40 mm Hg and measured by GAT and Tono-pen following standard
      protocols. The corneas were dissected and uniaxial tensile tests were performed
      on corneal strips. The correlation between GAT and Tono-pen errors and corneal
      secant modulus was evaluated using Pearson correlation coefficients. The
      influence of corneal thickness and the true pressure was also examined. RESULTS:
      At a true IOP of 10, 15, 20, 30, and 40 mm Hg, the GAT readings were 1.1 +/- 1.0,
      5.1 +/- 1.5, 9.5 +/- 2.0, 17.3 +/- 1.6, and 25.3 +/- 1.8 mm Hg, respectively. The
      corresponding Tono-pen readings were 7.8 +/- 1.7, 12.4 +/- 1.7, 16.1 +/- 1.9,
      22.5 +/- 2.1, and 28.1 +/- 2.2 mm Hg, respectively. The mean secant modulus at 1%
      strain of the canine corneal strips was 1.54 +/- 0.43 megapascal (MPa). Corneal
      secant modulus was significantly correlated with GAT errors when the true IOP was
      30 mm Hg (R = 0.49; P < 0.05). No significant correlation was observed between
      tonometric errors and corneal thickness. Both GAT and Tono-pen errors increased
      significantly at higher pressures (P < 0.001). CONCLUSIONS: Both GAT and Tono-pen
      underestimated IOP in canine eyes. There was preliminary experimental evidence
      for a correlation between corneal modulus and GAT in the canine eyes and a higher
      corneal modulus was associated with higher GAT readings at a certain pressure
      level. The tonometric errors appeared to be pressure-dependent.

PMID- 21896863
TI  - Histological and confocal microscopy changes in chronic corneal edema:
      implications for endothelial transplantation.
AB  - PURPOSE: To report in vivo confocal microscopic (IVCM) features in corneal edema
      supported by histopathologic correlation. METHODS: This was an observational
      study with evaluation of diagnostic technology. Twenty patients with clinically
      diagnosed corneal edema were involved, including 11 with Fuchs' endothelial
      dystrophy (FED). All cases, in addition to a control group of six normal eyes,
      were examined with IVCM before keratoplasty. Four eyes were examined after
      surgery. Thirteen corneal samples obtained by penetrating keratoplasty were
      examined by light and/or electron microscopy. IVCM and histopathologic sections
      were then analyzed for correlation and proper interpretation. Seven patients
      underwent Descemet's stripping endothelial keratoplasty (DSEK). RESULTS:
      Subepithelial fibroblasts were seen histologically and with IVCM in 7 (53.8%) of
      13 full-thickness corneal samples. IVCM alone detected these changes in 11 (55%)
      subjects before surgery, as well as after postoperative clinical improvement.
      Other IVCM features included absent (30%) or reduced (70%) subbasal corneal
      nerves, expanded hyperreflective keratocyte cell bodies, and processes with small
      vacuoles and large extracellular lacunae (95%), seen on IVCM only. Endothelial
      changes with polymegathism and reduced cell density were seen in non-FED cases.
      CONCLUSIONS: This is the first study in which IVCM features of corneal edema have
      been compared in detail with histopathologic findings. Subepithelial fibroblasts,
      reduced subbasal corneal nerves, and stromal keratocyte morphology were well
      documented in this study. With increasing popularity of DSEK this work supports
      the role of IVCM in quantitative evaluation of corneal edema in early
      preoperative stages, as well as after surgery, when the cornea appear clinically,
      but not histologically, normal.

PMID- 21896864
TI  - Regulation of experimental autoimmune uveoretinitis by anti-delta-like ligand 4
      monoclonal antibody.
AB  - PURPOSE: To investigate the involvement of delta-like ligand (Dll)4 in the
      development of experimental autoimmune uveoretinitis (EAU) in B10.RIII mice.
      METHODS: B10.RIII mice were immunized with interphotoreceptor retinoid binding
      protein (IRBP) peptide 161-180 in complete Freund's adjuvant together with
      intraperitoneal injection of Bordetella pertussis toxin. mRNA expressions of
      Notch receptors and their ligands in the eye were evaluated. To investigate the
      involvement of Dll in EAU, anti-Dll1, anti-Dll4, or control antibody (Ab) was
      intraperitoneally injected during both the induction and the effector phases or
      only the effector phase. Alternatively, mice were intraperitoneally injected with
      gamma-secretase inhibitor (GSI) or the control vehicle during the induction
      phase. Fourteen days after immunization, the eyes and spleens were harvested. The
      eyes were used for histologic and/or cytokine mRNA expression analysis, whereas
      the spleens were used for flow cytometric analysis, and antigen-recall
      proliferation and cytokine assays. RESULTS: Expression of Notch1, 2, 4, and Dll4
      in the eye were upregulated by EAU induction. Anti-Dll4 Ab treatment during both
      the induction and effector phases, but not only the effector phase, significantly
      reduced the severity of EAU. IFN-gamma, IL-12p35, IL-17A, and TGF-beta mRNA
      expression in the eye were significantly attenuated by treatment with anti-Dll4
      Ab. Splenocytes from anti-Dll4 Ab-treated mice showed significantly less
      proliferation and IL-17 production on antigen stimulation. Also, the severity of
      EAU was significantly reduced by gamma-secretase inhibitor treatment during the
      induction phase. CONCLUSIONS; Dll4-mediated Notch signaling during the
      sensitization is critical for the development of EAU. This can be a novel
      prophylactic target for autoimmune uveitis.

PMID- 21896865
TI  - Regulation of cytosolic phospholipase A2 (cPLA2alpha) and its association with
      cell proliferation in human lens epithelial cells.
AB  - PURPOSE: To investigate the molecular mechanism for cytosolic phospholipase A2
      (cPLA(2)alpha) regulation and its association to platelet-derived growth factor
      (PDGF)-induced cell proliferation. METHODS: cPLA(2)alpha was examined using human
      lens epithelial (HLE) B3 cells. Reactive oxygen species (ROS) generation induced
      by PDGF was analyzed by luminescence assay. Cell proliferation was measured by
      cell counting and by BrdU assay. Human cPLA(2)alpha gene was cloned via RT-PCR
      followed by site-directed mutagenesis to construct HLE B3 cells expressing either
      inactive cPLA(2)alpha enzyme with S228A mutation (S228A), or cPLA(2)alpha
      truncated at the calcium-binding C2 domain (C2D). Activity of cPLA(2)alpha was
      measured by arachidonic acid (AA) release from cell membranes using [(3)H]
      arachidonic acid prelabeled cells. The effect of intracellular calcium level on
      cPLA(2)alpha function was examined by treating cells with ionomycin (calcium
      influx), thapsgargin (endoplasmic reticulum [ER] calcium store release) or 1,2
      bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (BAPTA; calcium
      chelator). Activation of extracellular signal-regulated kinases (ERK), JNK, p38,
      or Akt was detected by Western blot analysis using specific antibodies. RESULTS:
      S228A mutant showed suppressed PDGF-induced reactive oxygen species generation,
      ERK and JNK activation (no effect on p38 or Akt), and cell proliferation in
      comparison with the vector alone (Vec) control. Calcium-binding C2 domain cells
      lost the ability of membrane translocation and activation of cPLA(2)alpha. PDGF
      cell signaling was calcium-dependent, and the calcium was supplied either from
      the external flux or endoplasmic reticulum store. However, enrichment of cellular
      calcium not only augmented PDGF function, but also demonstrated a cPLA(2)alpha
      dependent calcium-signaling cascade that led to cell proliferation. CONCLUSIONS:
      cPLA(2)alpha is regulated by calcium mobilization and mitogen-activated protein
      kinases (MAPK) activation. Both PDGF mitogenic action and calcium signaling are
      cPLA(2)alpha-dependent.

PMID- 21896866
TI  - Vitronectin: a matrix support factor for human limbal epithelial progenitor
      cells.
AB  - PURPOSE: The authors recently developed a therapeutic technique for patients with
      limbal stem cell deficiency by harvesting ocular surface stem cells (SCs),
      expanding them on therapeutic contact lenses (CLs), and applying them to diseased
      corneas. The present study determined the proteins that bind to CLs and whether
      such factors, along with transplanted cells, are critical determinants for
      corneal rehabilitation using this method. METHODS: Therapeutic CLs were exposed
      to human serum, and adherent proteins were analyzed by proteomics. The
      distribution of vitronectin (VN) on the ocular surface was determined with
      specific antibodies. Cadaveric human corneas were chemically wounded, and cell
      transfer by CLs was assessed in organ culture. RESULTS: VN was identified as a
      serum factor that binds and desorbs from CLs. VN localized to the limbal and
      basement membranes (BM) of other SC-harboring organs. Clonogenic assays
      demonstrated higher colony-forming efficiency on VN compared with uncoated
      surfaces. Cell transfer from CLs was achieved through in vitro models and was
      abrogated by RGD peptides and inhibitory antibodies to VN and its receptor.
      CONCLUSIONS: Identification of VN within the limbal BM, its effect on limbal SC
      activity, and the discovery of this factor on serum-exposed CL polymers implies a
      role in supporting progenitor cells and facilitating corneal regeneration.

PMID- 21896867
TI  - Associations of complement factor H (CFH) and age-related maculopathy
      susceptibility 2 (ARMS2) genotypes with subtypes of polypoidal choroidal
      vasculopathy.
AB  - PURPOSE: To clarify whether complement factor H (CFH) and age-related maculopathy
      susceptibility 2 (ARMS2) genotypes are associated with subtypes of polypoidal
      choroidal vasculopathy (PCV), such as polypoidal choroidal neovascularization
      (CNV) and typical PCV. METHODS: Two hundred eighty-seven patients were
      categorized as having polypoidal CNV (85 patients) or typical PCV (202 patients)
      on the basis of indocyanine green angiographic findings. In total, 277 subjects
      without age-related macular degeneration (i.e., free of PCV and CNV), served as
      controls. I62V (rs800292) in the CFH gene and A69S (rs10490924) in the ARMS2 gene
      were genotyped, and case-control studies were performed in subjects with these
      PCV subtypes. RESULTS: The polypoidal CNV group included no subjects homozygous
      for the A/A genotype of rs800292, whereas 7% of the typical PCV group had this
      genotype. Case-control studies of polypoidal CNV and typical PCV showed
      significant differences in all distributions of rs10490924 between these two
      groups. In contrast, the distributions of rs10490924 did not differ between the
      typical PCV and control groups. Logistic regression analysis with adjustment for
      confounding factors showed the distributions of rs10490924 to differ
      significantly between the controls and polypoidal CNV cases (P = 2.1 * 10(-10);
      OR, 10.87). The T/T genotype was significantly more common in the polypoidal CNV
      than in the typical PCV group (P = 3.6 * 10(-14); OR, 19.61). CONCLUSIONS: PCV
      may be genetically divisible into polypoidal CNV and typical PCV. The rs800292
      variant of the CFH gene is a potential marker for typical CNV. The rs10490924
      variant of the ARMS2 gene was shown to be associated with polypoidal CNV. Typical
      PCV was not associated with this variant.

PMID- 21896868
TI  - Selective rod degeneration and partial cone inactivation characterize an
      iodoacetic acid model of Swine retinal degeneration.
AB  - PURPOSE. Transgenic pigs carrying a mutant human rhodopsin transgene have been
      developed as a large animal model of retinitis pigmentosa (RP). This model
      displays some key features of human RP, but the time course of disease
      progression makes this model costly, time consuming, and difficult to study
      because of the size of the animals at end-stage disease. Here, the authors
      evaluate an iodoacetic acid (IAA) model of photoreceptor degeneration in the pig
      as an alternative model that shares features of the transgenic pig and human RP.
      METHODS. IAA blocks glycolysis, thereby inhibiting photoreceptor function. The
      effect of the intravenous injection of IAA on swine rod and cone photoreceptor
      viability and morphology was followed by histologic evaluation of different
      regions of the retina using hematoxylin and eosin and immunostaining. Rod and
      cone function was analyzed by full-field electroretinography and multifocal
      electroretinography. RESULTS. IAA led to specific loss of rods in a central-to
      peripheral retinal gradient. Although cones were resistant, they showed shortened
      outer segments, loss of bipolar cell synaptic connections, and a diminished
      flicker ERG, hallmarks of transition to cone dysfunction in RP patients.
      CONCLUSIONS. IAA provides an alternative rod-dominant model of retinal damage
      that shares a surprising number of features with the pig transgenic model of RP
      and with human RP. This IAA model is cost-effective and rapid, ensuring that the
      size of the animals does not become prohibitive for end-stage evaluation or
      therapeutic intervention.

PMID- 21896869
TI  - Reevaluation of dystrophin localization in the mouse retina.
AB  - PURPOSE. The roles of dystrophins in retinal physiology remain elusive. The lack
      of proper clustering of the potassium channel Kir4.1 and of the aquaporin AQP4
      was proposed to be the basis of the ERG abnormality observed in many Duchenne
      muscular dystrophy (DMD) patients. However, the electroretinogram of Dp71-null
      mice, in which this clustering is disrupted, shows only a moderate reduction of
      the b-wave with no change in the implicit times. Additionally, the deficit in
      color discrimination found in DMD patients is hard to explain through the known
      expression of DMD gene products. The authors thus decided to reexamine their
      distribution in the mouse retina. METHODS. Messenger RNA distribution was
      assessed by PCR coupled to laser microdissection of the outer and inner nuclear
      layers and by in situ hybridization for Dp427. Mouse retinas were double labeled
      for dystrophins versus presynaptic and postsynaptic proteins or antibodies
      specific for Dp427 or Dp427+Dp260. RESULTS. Messengers for Dp427, Dp260, and
      Dp140 were present in the inner nuclear layer. Dp427 mRNA was further detected in
      bipolar cells and in some amacrine cells by in situ hybridization. Comparative
      labeling in wild-type and mdx(5Cv) retinas (lacking Dp427) indicated a
      differential distribution of Dp427 and Dp260 between rod and cone terminals.
      CONCLUSIONS. In addition to their localization in photoreceptor terminals, Dp427,
      Dp260, and Dp140 are expressed in inner nuclear layer neurons, notably in bipolar
      cells for Dp427. Dp427 was proportionally more expressed in cone- than in rod
      associated synapses compared with Dp260.

PMID- 21896870
TI  - Enhancement of axonal regeneration of retinal ganglion cells in adult rats by
      etomidate: involvement of protein kinase C.
AB  - PURPOSE: To investigate the effect of etomidate (ET) on axonal regeneration of
      retinal ganglion cells (RGCs) in adult rats. METHODS: The optic nerve was
      transected intraorbitally at 1 mm from the optic disc, and an autologous
      peripheral nerve was transplanted onto the ocular ON stump in adult rats. Then
      the animals were treated with ET, Go6976, ET combined with Go6976, phorbol-12
      myristate-13-acetate (PMA), or ET combined with PMA. Four weeks after grafting,
      the number of regenerating RGCs labeled retrogradely with neuronal retrograde
      tracer was counted in all animals, and the activity of membrane protein kinase C
      (mPKC) and cytoplasmic PKC (cPKC) was measured in ET-treated animals. RESULTS:
      The number of regenerating RGCs significantly increased when the dose of ET was
      increased from 2 mg/kg to 6 mg/kg, whereas the ratio of mPKC activity to cPKC
      activity significantly decreased in ET-treated animals. Go6976, a potent
      conventional PKC inhibitor, also significantly increased the number of
      regenerating RGCs. However, the number of regenerating RGCs in animals treated
      with Go6976 alone was significantly lower than in those treated with ET at 6
      mg/kg. Combined treatment with ET at 6 mg/kg and Go6976 did not increase the
      number of regenerating RGCs. In contrast, PMA, a potent PKC activator, partially
      abolished the positive effect of ET on the axonal regeneration of axotomized
      RGCs. CONCLUSIONS: These results suggest that ET promotes axonal regeneration of
      RGCs in adult rats, in part by inhibiting conventional PKC.

PMID- 21896871
TI  - Prevalence of primary open angle glaucoma in a rural adult Chinese population:
      the Handan eye study.
AB  - PURPOSE: To estimate the prevalence and associations of primary open angle
      glaucoma (POAG) in a rural population of northern China. METHODS: In a rural
      county in Handan, China, 6716 adults residing in 13 villages were randomly
      selected and participated in the study. All participants completed a
      comprehensive eye examination, including intraocular pressure (IOP), slit-lamp
      examination, and fundus evaluation. Visual fields were obtained with on glaucoma
      suspects. RESULTS: Sixty-five persons (1.2%) had POAG, with an adjusted
      prevalence of 1.0% (95% confidence interval [CI], 0.7% -1.3%) in those aged 40
      years and older. Sex was not significantly associated with POAG (P > 0.05). Age
      (odds ratio [OR], 1.9; 95% CI, 1.4-2.5, for each 10-year increase), IOP (OR, 1.5;
      95% CI 1.2-2.0 for each 5-mm Hg increase), axial length (OR, 1.3; 95% CI, 1.1
      1.6), and moderate myopia (3.1-6.0 D; OR, 4.7; 95% CI, 1.6-13.5) increased the
      risk for POAG in multivariate analysis. The mean IOP of persons with POAG was
      16.3 +/- 3.5 mm Hg, and 90% of them presented with an IOP <= 21 mm Hg. Of those
      with POAG, 4.5% were blind from glaucoma in at least one eye. CONCLUSIONS:
      Approximately 1% of adults aged 40 years and older living in rural China have
      POAG. As seen in other populations, increasing age, higher IOP, greater axial
      length, and having myopia were associated with POAG. Given the rapid aging and
      myopic shift (acquired myopia) in China's population, POAG is likely to increase
      in prevalence in the coming decades.

PMID- 21896872
TI  - Automated assessment of diabetic retinopathy severity using content-based image
      retrieval in multimodal fundus photographs.
AB  - PURPOSE: Recent studies on diabetic retinopathy (DR) screening in fundus
      photographs suggest that disagreements between algorithms and clinicians are now
      comparable to disagreements among clinicians. The purpose of this study is to (1)
      determine whether this observation also holds for automated DR severity
      assessment algorithms, and (2) show the interest of such algorithms in clinical
      practice. METHODS: A dataset of 85 consecutive DR examinations (168 eyes, 1176
      multimodal eye fundus photographs) was collected at Brest University Hospital
      (Brest, France). Two clinicians with different experience levels determined DR
      severity in each eye, according to the International Clinical Diabetic
      Retinopathy Disease Severity (ICDRS) scale. Based on Cohen's kappa (kappa)
      measurements, the performance of clinicians at assessing DR severity was compared
      to the performance of state-of-the-art content-based image retrieval (CBIR)
      algorithms from our group. RESULTS: At assessing DR severity in each patient,
      intraobserver agreement was kappa = 0.769 for the most experienced clinician.
      Interobserver agreement between clinicians was kappa = 0.526. Interobserver
      agreement between the most experienced clinicians and the most advanced algorithm
      was kappa = 0.592. Besides, the most advanced algorithm was often able to predict
      agreements and disagreements between clinicians. CONCLUSIONS: Automated DR
      severity assessment algorithms, trained to imitate experienced clinicians, can be
      used to predict when young clinicians would agree or disagree with their more
      experienced fellow members. Such algorithms may thus be used in clinical practice
      to help validate or invalidate their diagnoses. CBIR algorithms, in particular,
      may also be used for pooling diagnostic knowledge among peers, with applications
      in training and coordination of clinicians' prescriptions.

PMID- 21896873
TI  - Vitamin D and cardiovascular disease.
AB  - Vitamin D participates in numerous physiologic and pathologic processes. Most
      tissues have vitamin D receptors (VDRs), and vitamin D is an important regulator
      of gene expression. Approximately 1 billion people worldwide have insufficient
      levels of vitamin D. Deficiency has been associated with many chronic diseases,
      including cardiovascular disease (CVD), which is the leading cause of death in
      both men and women. A relationship between vitamin D and CVD is implicated;
      however studies show conflicting data. Epidemiologic evidence and observational
      studies demonstrate an association between vitamin D deficiency and CVD; however,
      this is not substantiated by randomized controlled trials (RCTs). Many questions
      remain unanswered, but growing evidence supports a beneficial role of vitamin D
      on cardiovascular health. Key teaching points: * Vitamin D influences many
      cellular functions. * A global pandemic of vitamin D deficiency exists. *
      Epidemiologic data and observational studies suggest that vitamin D deficiency
      may increase cardiovascular risk. * RCTs show no significant relationship
      (however, studies have significant limitations). * The association between
      vitamin D status and CVD is uncertain, but low vitamin D levels may be an
      independent and modifiable CV risk factor.

PMID- 21896874
TI  - Effect of calcium carbonate particle size on calcium absorption and retention in
      adolescent girls.
AB  - OBJECTIVE: Increasing calcium bioavailability by decreasing calcium salt particle
      size in the supplement may be one way to increase calcium absorption. The aim of
      the study was to compare (1) large versus small particle size CaCO(3) supplements
      and (2) small particle size CaCO(3) supplement versus placebo on calcium
      absorption and retention in adolescent girls. METHODS: Thirty-one adolescent
      girls, aged 11 to 14 years, participated in two 3-week calcium balance periods
      separated by a 1-week washout period. During both balance periods, the subjects
      consumed a controlled diet containing 804 mg/d calcium. Using a crossover design,
      one group (n = 19) received an additional ~600 mg/d calcium of two ~300-mg
      calcium doses as either large particle (18 MUm; i.e., standard commercial form)
      or small particle (13.5 MUm) CaCO(3). A second group (n = 12) received ~600 mg/d
      calcium from small-particle CaCO(3) or placebo. RESULTS: The parathyroid hormone
      suppression curve, following a challenge, from the first arm of the study
      indicated that calcium absorption from the small particle size CaCO(3) was less
      than that from the large particle size CaCO(3). The parathyroid hormone
      suppression curve from the small particle versus placebo arm indicated that
      calcium absorption from small particle size CaCO(3) was greater than placebo.
      Calcium balance (Ca intake - [urine Ca + fecal Ca]) demonstrated that the small
      particle size CaCO(3) supplement increased Ca retention nearly 2-fold compared
      with placebo (p < 0.05; 496 +/- 213 and 256 +/- 94 mg/d, respectively). However,
      there was no significant difference in Ca retention due to small versus large
      particle size of CaCO(3) (p > 0.05; 349.1 +/- 131.6 and 322.0 +/- 194.2 mg/d,
      respectively). CONCLUSIONS: Dietary supplementation with CaCO(3) is effective in
      increasing calcium absorption and retention compared with placebo. But there is
      no advantage of small compared with large particle size CaCO(3) on calcium
      absorption and retention.

PMID- 21896875
TI  - Loss of taste responds to high-dose biotin treatment.
AB  - BACKGROUND AND OBJECTIVE: We saw 2 patients who lost their sense of taste, which
      was restored by pharmacologic doses of biotin. The key objective is to describe
      the 2 case reports and suggest a potential treatment for unexplained loss of
      taste. METHODS AND DESIGN: The first patient was a 67-year-old woman who lost her
      sense of taste taking Juvenon, a dietary herbal supplement containing acyl-L
      carnitine, lipoic acid, calcium, phosphorus, and biotin 300 MUg per day. The
      second patient was a 60-year-old man who lost his sense of taste after a sleeve
      gastrectomy for obesity. RESULTS: The first patient did not respond to 5 mg per
      day of biotin, but taste was restored with 10 mg of biotin per day. Biotin was
      prescribed based on information that lipoic acid bound to the biotin transporter.
      Baseline urine gave no evidence of a pre-existing biotin deficiency. The second
      patient did not have restoration of taste after taking biotin 5 mg per day for 7
      weeks but did have taste restoration on biotin 20 mg per day. Neither subject had
      an abnormal biotinidase level. CONCLUSIONS: Further research into the
      relationship of biotin to taste is clearly indicated. Loss of taste was very
      distressing and significantly altered the quality of life for both patients.
      Since biotin up to 40 mg per day has been shown to be safe, a therapeutic trial
      of pharmacologic doses of biotin should be considered as a potentially curative
      treatment in patients who present with a loss of taste that has no obvious cause.

PMID- 21896876
TI  - The Oslo health study: cheese intake was negatively associated with the metabolic
      syndrome.
AB  - OBJECTIVE: We previously reported that the frequency of cheese intake (FCI) was
      negatively associated with serum triglycerides and positively associated with
      high-density lipoprotein cholesterol (HDL), both components of the metabolic
      syndrome (MetS). We therefore wanted to study whether FCI is associated with
      MetS. METHODS: The Oslo Health Study (18,770 subjects), obtained data from 7815
      men and 9685 women on cheese intake and risk factors for MetS, except for fasting
      glucose. MetS requires central obesity and at least 2 of the following: increased
      triglycerides, low HDL cholesterol, increased systolic or diastolic blood
      pressure, and elevated fasting blood glucose. We calculated the index SumRisk,
      providing the number of MetS factors present, and MetSRisk to reflect the
      combined levels of many MetS factors. The association between FCI and MetSRisk
      (SumRisk) was studied using regression analyses. RESULTS: In young (30 years),
      middle-aged (40 and 45 years), seniors (59-60), and old (75-76 years) subjects,
      there was an inverse association between FCI and MetSRisk (p <= 0.005, except in
      old men). Using regression, we found a consistent negative association (p <
      0.001) between FCI and MetSRisk, SumRisk, single MetS components, and the
      complete MetS, prevailing after controlling for sex, age, time since last meal,
      intake of fruit/berries, fruit juice, fatty fish, coffee, alcohol, smoking,
      leisure time physical activity, years at school, and birthplace. FCI was also
      negatively associated with body mass index (p < 0.02), except in old women.
      CONCLUSION: Cheese intake can be negatively and independently associated with (1)
      an index including the level of many risk factors for MetS, (2) the number of
      MetS requirements present, (3) single MetS components, and (4) the complete MetS.

PMID- 21896877
TI  - Randomized placebo-controlled trial of guava juice as a source of ascorbic acid
      to reduce iron deficiency in Tarahumara indigenous schoolchildren of northern
      Mexico.
AB  - OBJECTIVE: Assess the efficacy of a 10-week consumption of guava juice on the
      iron status of children with mild iron deficiency anemia. METHODS: Ninety-five
      boarding school children aged 6-9 years identified as anemic were randomly
      allocated to receive 300 mL of natural guava juice containing ~200 mg of ascorbic
      acid (AA) or placebo (guava-flavored juice free of AA) with the main meal (5
      d/wk). Information about dietary intake was collected at weeks 3, 5, and 7 at
      school and household levels. Changes in hemoglobin (Hb) and plasma ferritin (PF)
      among the subsample iron deficient at baseline (n = 33) were the main outcomes.
      RESULTS: Iron and phytic acid intakes at school and at home did not differ
      between groups. Baseline Hb and PF were 11.9 +/- 0.5 g/dL and 8.2 +/- 3.6 ng/mL
      for the guava, and 11.4 +/- 1.1 g/dL and 7.4 +/- 4.6 ng/mL for the placebo group
      (Hb: p = 0.08; PF: p = 0.31); at week 10 of the study, corresponding values were
      13.1 +/- 0.9 g/dL and 17.9 +/- 10.3 ng/mL (n = 16), and 12.3 +/- 1.3 g/dL and
      15.4 +/- 5.8 ng/mL (n = 12) (Hb: p = 0.05; PF: p = 0.21). With analysis of
      variance (ANOVA) for repeated measures, the guava group had 0.64 g/dL higher Hb
      (CI(95), 0.18-1.11; p = 0.01) and 2.47 ng/mL higher PF (CI(95), -1.04 to 5.98; p
      = 0.12) compared with the placebo group. CONCLUSION: Guava juice providing 200 mg
      AA at one meal on each school day had a marginal effect on Hb and PF
      concentrations in children consuming high-phytate diets fortified with iron.

PMID- 21896878
TI  - Cholesterol ester and free fatty acids are modulated by policosanol in CaCo-2
      intestinal cells.
AB  - OBJECTIVE: To investigate policosanol absorption by brush border membrane (BBM),
      metabolism in CaCo-2 enterocytes, and transport of policosanol metabolites across
      the basolateral membrane (BLM). It was hypothesized that policosanol is partially
      oxidized into fatty acids and then is incorporated into other lipids. METHODS:
      Policosanol was emulsified with phosphatidylcholine in the culture medium. The
      viability of cells was assessed via an MTT (3-[4,5]dimethylthiazol-2-yl-2,5
      diphenyltetrazolim) assay. Control cells received only the same amount of
      "vehicle" (phosphatidylcholine) without policosanol. CaCo-2 cell monolayer and
      medium were collected; lipid was extracted and analyzed by thin-layer
      chromatography (TLC) and gas liquid chromatography (GLC). RESULTS: Eighty-six
      percent of policosanol added to the cell culture medium was absorbed after 48
      hours' incubation. The amount of cholesterol ester fatty acid was significantly
      increased both in the cells and in the basolateral medium, and was reduced in the
      apical medium. Policosanol increased the quantity of free fatty acids in the
      basolateral medium and reduced the free fatty acid content of CaCo-2 cells.
      Further evaluation of lipid profiles indicated that policosanol modulated the
      fatty acid profile of cholesterol ester in the basolateral medium. CONCLUSION: It
      was concluded that policosanol or policosanol metabolites may modulate lipid
      metabolism and/or transport following absorption by the BBM, partial oxidation by
      the intestinal epithelium, and transport of policosanol metabolites across the
      BLM.

PMID- 21896879
TI  - Effect of folic acid supplementation on homocysteine, serum total antioxidant
      capacity, and malondialdehyde in patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: Metformin is widely used in patients with type 2 diabetes, but it may
      decrease vitamin B12 and folate levels and increase levels of homocysteine (Hcy).
      Hyperhomocysteinemia (HHC) and hyperglycemia induce oxidative stress in type 2
      diabetes. Thus, this study was performed to determine the effects of folate
      supplementation on the concentration of homocysteine, total antioxidant capacity
      (TAC), and malondialdehyde (MDA). METHODS: This was a double-blind randomized
      controlled clinical trial. Sixty-eight men with type 2 diabetes participated in
      the study with written consent. Patients were divided randomly into 2 groups:
      folic acid 5 mg/d and placebo. All patients received the tablets for 8 weeks.
      Anthropometric and nutrient intake data were obtained from each patient. Baseline
      and eighth-week homocysteine, total antioxidant capacity, malondialdehyde,
      folate, and B12 levels were measured. RESULTS: After folate supplementation in
      the folic acid group, homocysteine was significantly decreased (15.1 +/- 3.2 to
      12.1 +/- 3.1 MUmol/L, p < 0.001) and folate and B12 levels were significantly
      increased (p < 0.001). A significant increase in total antioxidant capacity (0.96
      +/- 0.2 to 1.14 +/- 0.3 mmol Fe2+/L, p < 0.001) and a significant decrease in
      malondialdehyde (2.6 +/- 0.7 to 1.7 +/- 0.2 MUmol/L, p < 0.001) were observed in
      the folic acid group, whereas no significant changes occurred in the placebo
      group (p > 0.05). CONCLUSION: Pharmacological doses of folate supplementation
      lowered plasma homocysteine and serum malondialdehyde levels and improved serum
      total antioxidant capacity and folate and B12 levels in patients with type 2
      diabetes.

PMID- 21896880
TI  - Prevalence of high blood pressure among young rural adults in relation to height
      in childhood and adult body mass index.
AB  - OBJECTIVE: Evidence, mostly based on developed countries, indicates that disease
      risks may be associated with changes in growth processes rather than a one-point
      phenomenon. In view of the increasing prevalence of hypertension in India, there
      is a need to understand how patterns of growth during early childhood and
      adolescence influence blood pressure in adulthood, particularly among rural
      populations in India. METHODS: The risk of hypertension was examined in 378 rural
      men older than 20 years who were measured for anthropometry during early
      childhood, adolescence, and as young adults in a community-based cohort study.
      RESULTS: At the young age of 24 years, 33.9% of men had either high systolic
      blood pressure (>=130 mmHg) or high diastolic blood pressure (>=85 mmHg), even in
      absence of obesity. The growth of the subjects during childhood, in whom blood
      pressure developed later in young adulthood, was characterized by higher body
      mass index (BMI) throughout early childhood and adolescence as compared with
      those who had normal blood pressure. The prevalence of high blood pressure,
      especially diastolic, at this adult age was strongly associated with stunting at
      3+ years of age (<-2 SD height of the World Health Organization standard), and
      risk increased (odds ratio, 12.21; 95% confidence interval, 2.93-50.90; p <
      0.001) among those having high BMI (>=23 kg/m(2)) at adult age as compared with
      those who were not stunted in early life with a low BMI at adult age.
      CONCLUSIONS: The primary prevention of the epidemic of high blood pressure in
      India may require measures to prevent children from being stunted in early
      childhood and also prevent them from being overweight at young adulthood.

PMID- 21896881
TI  - A wheat homolog of MOTHER OF FT AND TFL1 acts in the regulation of germination.
AB  - Seed dormancy is an adaptive mechanism and an important agronomic trait.
      Temperature during seed development strongly affects seed dormancy in wheat
      (Triticum aestivum) with lower temperatures producing higher levels of seed
      dormancy. To identify genes important for seed dormancy, we used a wheat
      microarray to analyze gene expression in embryos from mature seeds grown at lower
      and higher temperatures. We found that a wheat homolog of MOTHER OF FT AND TFL1
      (MFT) was upregulated after physiological maturity in dormant seeds grown at the
      lower temperature. In situ hybridization analysis indicated that MFT was
      exclusively expressed in the scutellum and coleorhiza. Mapping analysis showed
      that MFT on chromosome 3A (MFT-3A) colocalized with the seed dormancy
      quantitative trait locus (QTL) QPhs.ocs-3A.1. MFT-3A expression levels in a
      dormant cultivar used for the detection of the QTL were higher after
      physiological maturity; this increased expression correlated with a single
      nucleotide polymorphism in the promoter region. In a complementation analysis,
      high levels of MFT expression were correlated with a low germination index in T1
      seeds. Furthermore, precocious germination of isolated immature embryos was
      suppressed by transient introduction of MFT driven by the maize (Zea mays)
      ubiquitin promoter. Taken together, these results suggest that MFT plays an
      important role in the regulation of germination in wheat.

PMID- 21896882
TI  - Functional network construction in Arabidopsis using rule-based machine learning
      on large-scale data sets.
AB  - The meta-analysis of large-scale postgenomics data sets within public databases
      promises to provide important novel biological knowledge. Statistical approaches
      including correlation analyses in coexpression studies of gene expression have
      emerged as tools to elucidate gene function using these data sets. Here, we
      present a powerful and novel alternative methodology to computationally identify
      functional relationships between genes from microarray data sets using rule-based
      machine learning. This approach, termed "coprediction," is based on the
      collective ability of groups of genes co-occurring within rules to accurately
      predict the developmental outcome of a biological system. We demonstrate the
      utility of coprediction as a powerful analytical tool using publicly available
      microarray data generated exclusively from Arabidopsis thaliana seeds to compute
      a functional gene interaction network, termed Seed Co-Prediction Network
      (SCoPNet). SCoPNet predicts functional associations between genes acting in the
      same developmental and signal transduction pathways irrespective of the
      similarity in their respective gene expression patterns. Using SCoPNet, we
      identified four novel regulators of seed germination (ALTERED SEED GERMINATION5,
      6, 7, and 8), and predicted interactions at the level of transcript abundance
      between these novel and previously described factors influencing Arabidopsis seed
      germination. An online Web tool to query SCoPNet has been developed as a
      community resource to dissect seed biology and is available at
      http://www.vseed.nottingham.ac.uk/.

PMID- 21896883
TI  - SLCO transport genes in prostate cancer--letter.

PMID- 21896884
TI  - Posterior crossbite and temporomandibular disorders (TMDs): need for orthodontic
      treatment?
AB  - The aim of this work was to update the bibliography regarding the concept of
      'temporomandibular disorder (TMD)' and 'posterior crossbite' and try to find out
      if there is any association between some special signs/symptoms of TMD and type
      of posterior crossbite. A literature search from 1970 to 2009, due to specified
      criterion, resulted in 14 publications that were found to be relevant for the
      present systematic review. An association between TMD and posterior crossbite
      (Yes-group) was reported as often as absence of such a relationship (No-group).
      The samples in the two groups showed similarities as well as differences with
      respect to number, gender, and age. Most articles reported only on 'presence' or
      'absence' of crossbite and only few on type of crossbite opposite to a thorough
      account of clinical signs and symptoms of TMD. This review seems, however, to
      state that a functional posterior crossbite (mandibular guidance with midline
      deviation) is associated with headache, temporomandibular joint and muscular
      pain, and clicking. As evident from the discussion, such type needs orthodontic
      treatment to rehabilitate the asymmetric muscular activity between the crossbite
      and non-crossbite sides and the changed condyle/temporal relationship caused by
      mandibular deviation. Whether this treatment also will avoid future TMD problems
      can be answered only after clinical follow-up studies have been performed.

PMID- 21896885
TI  - Vitamin E decreased the activity of acetylcholinesterase and level of lipid
      peroxidation in brain of rats exposed to aged and diluted sidestream smoke.
AB  - INTRODUCTION: The biological systems of both smoker and passive smoking suffer
      changes caused by toxic compounds from cigarette smoke such as inflammation,
      lipid peroxidation, and deficiency of vitamin E. The aim of the present study was
      to evaluate the effect of vitamin E on acetylcholinesterase (AChE) activity and
      the lipid peroxidation level in the brain of rats in the model of exposure to
      aged and diluted sidestream smoke (ADSS). METHODS: Adult male Wistar rats (200
      300 g) were exposed to ADSS for 4 weeks and treated with vitamin E (50 mg/kg/day)
      loaded by gavage. In the first, second, third, and fourth weeks, animals were
      concomitantly exposed to the smoke of 1, 2, 3, and 4 cigarettes/day,
      respectively. The duration of each exposure was 15 min, daily. RESULTS: For rats
      exposed to ADSS, the AChE activity and lipid peroxidation level increased in the
      striatum, cerebral cortex, and cerebellum. In contrast, the activity of AChE and
      the level of lipid peroxidation decreased in the smoke group treated with vitamin
      E. CONCLUSIONS: The results suggest that the rats exposed to ADSS and treated
      with vitamin E significantly reduced the raised activity of AChE and level lipid
      peroxidation from the brain structures studied. The study, therefore, concludes
      that vitamin E could be considered as a therapeutic agent in this type of
      exposure.

PMID- 21896886
TI  - Examining hookah smoking among a cohort of adolescent ever smokers.
AB  - INTRODUCTION: Evidence suggests that hookah smoking is growing among adolescents,
      particularly among those with a history of cigarette smoking, and is an emerging
      public health concern. We examined hookah use and its correlates among a sample
      of adolescents who have ever smoked and may be considered high risk for hookah
      use. METHODS: We examined differences between hookah users and nonusers among a
      cohort of 951 adolescents (75.3% of the baseline sample, mean age 17.6 years at
      24 months), consisting exclusively of youth who reported ever smoking cigarettes
      who were participating in a longitudinal study of adolescent smoking predictors
      and patterns. Ever and 30-day hookah use were assessed at 24 months. RESULTS: Of
      the 951 participants, 58.5% reported ever use and 30.2% reported smoking hookah
      at least 1 day in the past 30 days. Multivariate logistic regression analyses
      found that 30-day hookah use was associated with sex (p < .05); race (p < .001);
      current cigarette (p < .0001), cigar (p < .01), kretek (p < .05), and alcohol use
      (p < .01); and attending a hookah bar, lounge, or restaurant (p < .001).
      Participants who were male, White, and were concurrent users of multiple tobacco
      products and other substances had increased odds of 30-day hookah use.
      CONCLUSIONS: Prevalence of hookah use is high among youth who have already tried
      cigarette smoking and is associated with a variety of tobacco and other substance
      use behaviors. Evidence-based programs may be needed to prevent initiation of or
      reduce Hookah smoking, as well as address cooccurring problem behaviors, to
      lessen the health risks associated with use among adolescents.

PMID- 21896888
TI  - Capturing metabolite channeling in metabolic flux phenotypes.

PMID- 21896887
TI  - Multiple lines of evidence localize signaling, morphology, and lipid biosynthesis
      machinery to the mitochondrial outer membrane of Arabidopsis.
AB  - The composition of the mitochondrial outer membrane is notoriously difficult to
      deduce by orthology to other organisms, and biochemical enrichments are
      inevitably contaminated with the closely associated inner mitochondrial membrane
      and endoplasmic reticulum. In order to identify novel proteins of the outer
      mitochondrial membrane in Arabidopsis (Arabidopsis thaliana), we integrated a
      quantitative mass spectrometry analysis of highly enriched and prefractionated
      samples with a number of confirmatory biochemical and cell biology approaches.
      This approach identified 42 proteins, 27 of which were novel, more than doubling
      the number of confirmed outer membrane proteins in plant mitochondria and
      suggesting novel functions for the plant outer mitochondrial membrane. The novel
      components identified included proteins that affected mitochondrial morphology
      and/or segregation, a protein that suggests the presence of bacterial type lipid
      A in the outer membrane, highly stress-inducible proteins, as well as proteins
      necessary for embryo development and several of unknown function. Additionally,
      proteins previously inferred via orthology to be present in other compartments,
      such as an NADH:cytochrome B5 reductase required for hydroxyl fatty acid
      accumulation in developing seeds, were shown to be located in the outer membrane.
      These results also revealed novel proteins, which may have evolved to fulfill
      plant-specific requirements of the mitochondrial outer membrane, and provide a
      basis for the future functional characterization of these proteins in the context
      of mitochondrial intracellular interaction.

PMID- 21896889
TI  - Expression of enzymes involved in chlorophyll catabolism in Arabidopsis is light
      controlled.
AB  - We found that the levels of mRNA of two enzymes involved in chlorophyll
      catabolism in Arabidopsis (Arabidopsis thaliana), products of two chlorophyllase
      genes, AtCLH1 and AtCLH2, dramatically increase (by almost 100- and 10-fold,
      respectively) upon illumination with white light. The measurements of photosystem
      II quantum efficiency in 3-(3,4-dichlorophenyl)-1,1-dimethylurea-inhibited leaves
      show that their expression is not related to photosynthesis but mediated by
      photoreceptors. To identify the photoreceptors involved, we used various light
      treatments and Arabidopsis photoreceptor mutants (cry1, cry2, cry1cry2, phot1,
      phot2, phot1phot2, phyA phyB, phyAphyB). In wild-type Columbia, the amount of
      transcripts of both genes increase after white-light irradiation but their
      expression profile and the extent of regulation differ considerably. Blue and red
      light is active in the case of AtCLH1, whereas only blue light raises the AtCLH2
      mRNA level. The fundamental difference is the extent of up-regulation, higher by
      one order of magnitude in AtCLH1. Both blue and red light is active in the
      induction of AtCLH1 expression in all mutants, pointing to a complex control
      network and redundancy between photoreceptors. The blue-specific up-regulation of
      the AtCLH2 transcript is mediated by cryptochromes and modulated by phototropin1
      and phytochromes. Individually darkened leaves were used to test the effects of
      senescence on the expression of AtCLH1 and AtCLH2. The expression profile of
      AtCLH1 remains similar to that found in nonsenescing leaves up to 5 d after
      darkening. In contrast, the light induction of AtCLH2 mRNA declines during dark
      treatment. These results demonstrate that the expression of enzymes involved in
      chlorophyll catabolism is light controlled.

PMID- 21896890
TI  - Chromosomes carrying meiotic avoidance loci in three apomictic eudicot Hieracium
      subgenus Pilosella species share structural features with two monocot apomicts.
AB  - The LOSS OF APOMEIOSIS (LOA) locus is one of two dominant loci known to control
      apomixis in the eudicot Hieracium praealtum. LOA stimulates the differentiation
      of somatic aposporous initial cells after the initiation of meiosis in ovules.
      Aposporous initial cells undergo nuclear proliferation close to sexual
      megaspores, forming unreduced aposporous embryo sacs, and the sexual program
      ceases. LOA-linked genetic markers were used to isolate 1.2 Mb of LOA-associated
      DNAs from H. praealtum. Physical mapping defined the genomic region essential for
      LOA function between two markers, flanking 400 kb of identified sequence and
      central unknown sequences. Cytogenetic and sequence analyses revealed that the
      LOA locus is located on a single chromosome near the tip of the long arm and
      surrounded by extensive, abundant complex repeat and transposon sequences.
      Chromosomal features and LOA-linked markers are conserved in aposporous Hieracium
      caespitosum and Hieracium piloselloides but absent in sexual Hieracium pilosella.
      Their absence in apomictic Hieracium aurantiacum suggests that meiotic avoidance
      may have evolved independently in aposporous subgenus Pilosella species. The
      structure of the hemizygous chromosomal region containing the LOA locus in the
      three Hieracium subgenus Pilosella species resembles that of the hemizygous
      apospory-specific genomic regions in monocot Pennisetum squamulatum and Cenchrus
      ciliaris. Analyses of partial DNA sequences at these loci show no obvious
      conservation, indicating that they are unlikely to share a common ancestral
      origin. This suggests convergent evolution of repeat-rich hemizygous chromosomal
      regions containing apospory loci in these monocot and eudicot species, which may
      be required for the function and maintenance of the trait.

PMID- 21896893
TI  - Bisphosphonates for osteoporosis: benefits and risks.

PMID- 21896896
TI  - Approach to the hospitalized patient with severe insulin resistance.
AB  - Glucose control improves outcomes in the hospitalized patient, particularly
      patients on prolonged ventilator support, after acute myocardial infarction or
      after coronary artery bypass surgery. An iv insulin algorithm is the standard of
      care for initial treatment of significant hyperglycemia in the hospitalized
      patient, and it can be transitioned to periodic sc insulin once the patient is
      more stable. However, illness, medications, the endocrine and inflammatory
      response to stress, and pain can all contribute to insulin resistance and further
      aggravate preexisting insulin resistance caused by obesity. Glucose treatment
      goals have been established to guide the rapy, but achieving those goals can be
      more challenging in the presence of severe insulin resistance. When target
      glucose values are not achieved with established insulin algorithms, the
      practitioner should evaluate for potential causes of insulin resistance from
      technical factors that cause "pseudo-insulin resistance" as well as other
      modifiable factors, such as electrolyte disorders, parenteral and enteral
      nutrition, or other medications. Published glucose guidelines provide glucose
      "goals" to guide changes in the insulin algorithm, but these goals may be
      difficult to achieve in all individuals. We propose a stepwise approach to
      evaluate and treat severe insulin resistance in the hospitalized patient in order
      to achieve glucose goals in a timely fashion.

PMID- 21896895
TI  - Update: Hypogonadotropic hypogonadism in type 2 diabetes and obesity.
AB  - Studies over the last few years have clearly established that at least 25% of men
      with type 2 diabetes have subnormal free testosterone concentrations in
      association with inappropriately low LH and FSH concentrations. Another 4% have
      subnormal testosterone concentrations with elevated LH and FSH concentrations.
      The Endocrine Society, therefore, now recommends the measurement of testosterone
      in patients with type 2 diabetes on a routine basis. The subnormal testosterone
      concentrations are not related to glycosylated hemoglobin or duration of
      diabetes, but are associated with obesity, very high C-reactive protein
      concentrations, and mild anemia. In addition, subnormal testosterone
      concentrations in these men are associated with a two to three times elevated
      risk of cardiovascular events and death in two early studies. Short-term studies
      of testosterone therapy in hypogonadal men with type 2 diabetes have demonstrated
      an increase in insulin sensitivity and a decrease in waist circumference.
      However, the data on the effect of testosterone replacement on glycemic control
      and cardiovascular risk factors such as cholesterol and C-reactive protein
      concentrations are inconsistent. As far as sexual function is concerned,
      testosterone treatment increases libido but does not improve erectile dysfunction
      and thus, phosphodiesterase inhibitors may be required. Trials of a longer
      duration are clearly required to definitively establish the benefits and risks of
      testosterone replacement in patients with type 2 diabetes and low testosterone.

PMID- 21896897
TI  - Retrocardiac catecholamine-producing paraganglioma.

PMID- 21896898
TI  - Double-barreled assault by aldosterone and salt on the heart.

PMID- 21896899
TI  - The coming of age of ultrasound-guided percutaneous ethanol ablation of selected
      neck nodal metastases in well-differentiated thyroid carcinoma.

PMID- 21896903
TI  - Analysis of the functional contributions of Asn233 in metallo-beta-lactamase IMP
      1.
AB  - Metallo-beta-lactamases, such as IMP-1, are a major global health threat, as they
      provide for bacterial resistance to a wide range of beta-lactam antibiotics,
      including carbapenems. Understanding the molecular details of the enzymatic
      process and the sequence requirements for function are essential aids in
      overcoming beta-lactamase-mediated resistance. An asparagine residue is conserved
      at position 233 in approximately 67% of all metallo-beta-lactamases. Despite its
      conservation, the molecular basis of Asn233 function is poorly understood and
      remains controversial. It has previously been shown that mutations at this site
      exhibit context-dependent sequence requirements in that the importance of a given
      amino acid depends on the antibiotic being tested. To provide a more thorough
      examination as to the function and sequence requirements at this position, a
      collection of IMP-1 mutants encoding each of the 19 possible amino acid
      substitutions was generated. The resistance levels toward four beta-lactam
      antibiotics were measured for Escherichia coli containing each of these mutants.
      The sequence requirements at position 233 for wild-type levels of resistance
      toward two cephalosporins were the most relaxed, while there were more stringent
      sequence requirements for resistance to ampicillin or imipenem. Enzyme kinetic
      analysis and determinations of steady-state protein levels indicated that the
      effects of the substitutions on resistance are due to changes in the kinetic
      parameters of the enzyme. Taken together, the results indicate that substitutions
      at position 233 significantly alter the kinetic parameters of the enzyme, but
      most substituted enzymes are able to provide for a high level of resistance to a
      broad range of beta-lactams.

PMID- 21896904
TI  - TMC310911, a novel human immunodeficiency virus type 1 protease inhibitor, shows
      in vitro an improved resistance profile and higher genetic barrier to resistance
      compared with current protease inhibitors.
AB  - TMC310911 is a novel human immunodeficiency virus type 1 (HIV-1) protease
      inhibitor (PI) structurally closely related to darunavir (DRV) but with improved
      virological characteristics. TMC310911 has potent activity against wild-type (WT)
      HIV-1 (median 50% effective concentration [EC(50)], 14 nM) and a wide spectrum of
      recombinant HIV-1 clinical isolates, including multiple-PI-resistant strains with
      decreased susceptibility to currently approved PIs (fold change [FC] in EC(50),
      >10). For a panel of 2,011 recombinant clinical isolates with decreased
      susceptibility to at least one of the currently approved PIs, the FC in TMC310911
      EC(50) was <= 4 for 82% of isolates and <= 10 for 96% of isolates. The FC in
      TMC310911 EC(50) was <= 4 and <= 10 for 72% and 94% of isolates with decreased
      susceptibility to DRV, respectively. In vitro resistance selection (IVRS)
      experiments with WT virus and TMC310911 selected for mutations R41G or R41E, but
      selection of resistant virus required a longer time than IVRS performed with WT
      virus and DRV. IVRS performed with r13025, a multiple-PI-resistant recombinant
      clinical isolate, and TMC310911 selected for mutations L10F, I47V, and L90M (FC
      in TMC310911 EC(50) = 16). IVRS performed with r13025 in the presence of DRV
      required less time and resulted in more PI resistance-associated mutations (V32I,
      I50V, G73S, L76V, and V82I; FC in DRV EC(50) = 258). The activity against a
      comprehensive panel of PI-resistant mutants and the limited in vitro selection of
      resistant viruses under drug pressure suggest that TMC310911 represents a
      potential drug candidate for the management of HIV-1 infection for a broad range
      of patients, including those with multiple PI resistance.

PMID- 21896905
TI  - Enhanced neutralization of HIV by antibodies displayed on the S-layer of
      Caulobacter crescentus.
AB  - Innovative methods of prevention are needed to stop the more than two million new
      HIV-1 infections annually, particularly in women. Local application of anti-HIV
      antibodies has been shown to be effective at preventing infection in nonhuman
      primates; however, the concentrations needed are cost prohibitive. Display of
      antibodies on a particulate platform will likely prolong effectiveness of these
      anti-HIV agents and lower the cost of goods. Here, we demonstrate that the
      bacterium Caulobacter crescentus and its highly expressed surface-layer (S-layer)
      protein can provide this antibody display platform. Caulobacters displaying
      protein G, alone or with CD4 codisplay, successfully captured HIV-1-specific
      antibodies and demonstrated functional neutralization. Compared to soluble
      antibodies, a neutralizing anti-HIV antibody displayed on Caulobacter was as
      effective or more effective at neutralizing diverse HIV-1 isolates. Moreover,
      when an antibody reactive with an epitope induced by CD4 binding (CD4i) was
      codisplayed with CD4, there was significant enhancement in HIV-1 neutralization.
      These results suggest that caulobacters displaying anti-HIV antibodies offer a
      distinct improvement in the use of antibodies as microbicides. Furthermore, these
      reagents can specifically evaluate anti-HIV antibodies in concert with other HIV
      1 blocking agents to assess the most suitable tools for conversion to scFvs,
      allowing for direct display within the S-layer protein and further reducing cost
      of goods. In summary, C. crescentus, which can be easily produced and chemically
      stabilized at low cost, is well suited for engineering as an effective platform,
      offering an inexpensive way to produce and deliver HIV-1-specific microbicides.

PMID- 21896906
TI  - Development of dual-acting pyrimidinediones as novel and highly potent topical
      anti-HIV microbicides.
AB  - In the absence of an effective vaccine against the human immunodeficiency virus
      (HIV), topical microbicides to prevent the sexual transmission of HIV represent
      an important strategy to prevent the continued spread of infection. The recent
      trend in the development of new microbicide candidates includes the utilization
      of FDA-approved therapeutic drugs that target the early stages of the HIV life
      cycle, including entry inhibitors and reverse transcriptase inhibitors. We have
      investigated 12 pyrimidinedione compounds with potent HIV activities and their
      abilities to inhibit both virus entry and reverse transcription, in an effort to
      determine a lead microbicide for product development. The candidate compounds
      were evaluated for efficacy against subtype B, C, and E clinical virus strains in
      fresh human peripheral blood mononuclear cells and against CCR5-tropic virus
      strains in both monocyte-macrophages and dendritic cells. Microbicide-specific
      biological assays and toxicity evaluations were also performed in a variety of
      established and fresh human cells as well as against Lactobacillus strains common
      to the vaginal environment. These evaluations resulted in the identification of
      congeners with cyclopropyl and cyclobutyl substituents at the N-1 of the
      pyrimidinedione as the most active molecules in the structure-activity
      relationship series. The pyrimidinediones represent excellent microbicide
      candidates in light of their significantly high efficacies against HIV-1
      (subnanomolar concentration range), potencies (therapeutic index, >1 million),
      solubility profiles, and dual mechanism of antiviral action that includes two
      early steps of virus replication prior to the integration of the virus that are
      considered most important for microbicidal activity.

PMID- 21896907
TI  - Pharmacokinetic mismatch does not lead to emergence of isoniazid- or rifampin
      resistant Mycobacterium tuberculosis but to better antimicrobial effect: a new
      paradigm for antituberculosis drug scheduling.
AB  - Multidrug resistant-tuberculosis is a pressing problem. One of the major
      mechanisms proposed to lead to the emergence of drug resistance is
      pharmacokinetic mismatch. Stated as a falsifiable hypothesis, the greater the
      pharmacokinetic mismatch between rifampin and isoniazid, the higher the isoniazid
      and rifampin-resistant subpopulation sizes become with time. To test this, we
      performed hollow-fiber-system studies for both bactericidal and sterilizing
      effects in experiments of up to 42 days. We mimicked pharmacokinetics of 600
      mg/day rifampin and 300-mg/day isoniazid administered to patients. Rifampin was
      administered first, followed by isoniazid 0, 6, 12, and 24 h later. The treatment
      was for drug-susceptible Mycobacterium tuberculosis in some experiments and
      hollow fiber systems with inoculum preseeded with isoniazid- and rifampin
      resistant isogenic Mycobacterium tuberculosis strains in others. Analysis of
      variance revealed that the 12-h and 24-h-mismatched regimens always killed better
      than the matched regimens during both bactericidal and sterilizing effects (P <
      0.05). This means that either the order of scheduling or the sequential
      administration of drugs in combination therapy may lead to significant
      improvement in microbial killing. Rifampin-resistant and isoniazid-resistant
      subpopulations were not significantly higher with increased mismatching in
      numerous analysis-of-variance comparisons. Thus, the pharmacokinetic mismatch
      hypothesis was rejected. Instead, sequential administration of anti-tuberculosis
      (TB) drugs (i.e., deliberate mismatch) following particular schedules suggests a
      new paradigm for accelerating M. tuberculosis killing. We conclude that current
      efforts aimed at better pharmacokinetic matching to decrease M. tuberculosis
      resistance emergence are likely futile and counterproductive.

PMID- 21896908
TI  - Excretion of moxidectin into breast milk and pharmacokinetics in healthy
      lactating women.
AB  - Moxidectin, registered worldwide as a veterinary antiparasitic agent, is
      currently under development for humans for the treatment of onchocerciasis in
      collaboration with the World Health Organization. The objective of this study was
      to assess the pharmacokinetics of moxidectin in healthy lactating women,
      including the excretion into breast milk. Twelve women, ages 23 to 38 years,
      weighing 54 to 79 kg, all more than 5 months postpartum, were enrolled, following
      their plan to wean their infants and provision of informed consent. A single 8
      mg, open-label dose was administered orally after consumption of a standard
      breakfast. Complete milk collection was done for approximately 28 days, and
      plasma samples were collected for 90 days. Moxidectin concentrations were
      measured by high-performance liquid chromatography (HPLC) with fluorescence
      detection, with a validated range of 0.08 to 120 ng/ml. Noncompartmental
      pharmacokinetic methods were used to find the following results: peak
      concentration in plasma (C(max)), 87 +/- 25 ng/ml; time to C(max) (t(max)), 4.18
      +/- 1.59 h; terminal-phase elimination half-life (t(1/2)), 832 +/- 321 h; total
      area under the concentration-time curve (AUC), 4,046 +/- 1,796 ng . h/ml;
      apparent oral dose clearance (CL/F), 2.35 +/- 1.07 l/h; ratio of CL/F to the
      terminal-phase disposition rate constant, lambda(z) (Vlambda(z)/F), 2,526 +/- 772
      liters; percentage of maternal dose excreted in milk, 0.701 +/- 0.299%; absolute
      amount excreted in milk, 0.056 +/- 0.024 mg; relative infant dose, 8.73 +/- 3.17%
      of maternal dose assuming complete absorption; clearance in milk (CL(milk)),
      0.016 +/- 0.009 liter/h. Nine of 12 subjects reported adverse events, all of
      which were considered treatment emergent but not drug related and were mostly
      reported during the long outpatient period 8 to 90 days after dose
      administration. The most frequently reported adverse events were headache and
      nausea (n = 4), oropharyngeal pain (n = 2), rhinitis, viral pharyngitis, and
      viral upper respiratory tract infection (n = 2).

PMID- 21896909
TI  - Zanamivir pharmacokinetics and pulmonary penetration into epithelial lining fluid
      following intravenous or oral inhaled administration to healthy adult subjects.
AB  - Zanamivir serum and pulmonary pharmacokinetics were characterized following
      intravenous (i.v.) or oral inhaled administration. I.v. zanamivir was given as
      intermittent doses of 100 mg, 200 mg, and 600 mg every 12 h (q12h) for two doses
      or as a continuous infusion (6-mg loading dose followed by 3 mg/h for 12 h). Oral
      inhaled zanamivir (two 5-mg inhalations q12h for two doses) was evaluated as
      well. Each zanamivir regimen was administered to six healthy subjects with serial
      pharmacokinetic sampling. In addition, a single bronchoalveolar lavage (BAL)
      fluid sample was collected at various time points and used to calculate
      epithelial lining fluid (ELF) drug concentrations for each subject. For
      intermittent i.v. administration of 100 mg, 200 mg, and 600 mg zanamivir, the
      median zanamivir concentrations in ELF collected 12 h after dosing were 74, 146,
      and 419 ng/ml, respectively, each higher than the historic mean 50% inhibitory
      concentrations for the neuraminidases of wild-type strains of influenza A and B
      viruses. Median ELF/serum zanamivir concentration ratios ranged from 55 to 79%
      for intermittent i.v. administration (when sampled 12 h after the last dose) and
      43 to 45% for continuous infusion (when sampled 6 to 12 h after the start of the
      infusion). For oral inhaled zanamivir, the median zanamivir concentrations in ELF
      were 891 ng/ml for the first BAL fluid collection and 326 ng/ml for subsequent
      BAL fluid collections (when sampled 12 h after the last dose); corresponding
      serum drug concentrations were undetectable. This study demonstrates zanamivir's
      penetration into the human pulmonary compartment and supports the doses selected
      for the continuing development of i.v. zanamivir in clinical studies of
      influenza.

PMID- 21896910
TI  - Griffithsin has antiviral activity against hepatitis C virus.
AB  - Hepatitis C virus (HCV)-infected patients undergoing liver transplantation
      universally experience rapid reinfection of their new liver graft. Current
      treatment protocols do not prevent graft reinfection and, in addition, an
      accelerated disease progression is observed. In the present study, we have
      evaluated a novel strategy to prevent HCV infection using a lectin, griffithsin
      (GRFT) that specifically binds N-linked high-mannose oligosaccharides that are
      present on the viral envelope. The antiviral effect of GRFT was evaluated in
      vitro using the HCV pseudoparticle (HCVpp) and HCV cell culture (HCVcc) systems.
      We show here that preincubation of HCVpp and HCVcc with GRFT prevents infection
      of Huh-7 hepatoma cells. Furthermore, GRFT interferes with direct cell-to-cell
      transmission of HCV. GRFT acts at an early phase of the viral life cycle by
      interfering in a genotype-independent fashion with the interaction between the
      viral envelope proteins and the viral receptor CD81. The capacity of GRFT to
      prevent infection in vivo was evaluated using uPA(+/+)-SCID mice (uPA stands for
      urokinase-type plasminogen activator) that harbor human primary hepatocytes in
      their liver (chimeric mice). In this proof-of-concept trial, we demonstrated that
      GRFT can mitigate HCV infection of chimeric mice. Treated animals that did become
      infected demonstrated a considerable delay in the kinetics of the viral
      infection. Our data demonstrate that GRFT can prevent HCV infection in vitro and
      mitigate HCV infection in vivo. GRFT treatment of chronically infected HCV
      patients undergoing liver transplantation may be a suitable strategy to prevent
      infection of the liver allograft.

PMID- 21896912
TI  - Population pharmacokinetic/pharmacogenetic model for optimization of efavirenz
      therapy in Caucasian HIV-infected patients.
AB  - Despite extensive clinical experience with efavirenz (EFV), unpredictable
      interindividual variabilities in efficacy and toxicity remain important
      limitations associated with the use of this antiretroviral. The purpose of this
      study was to determine the factors affecting EFV pharmacokinetics and to develop
      a pharmacokinetic/pharmacogenetic (PK/PG) model in a Caucasian population of HIV
      infected patients. In total, 869 EFV plasma concentrations from 128 HIV-infected
      patients treated with EFV were quantitatively assessed using a validated high
      performance liquid chromatography technique. All patients were genotyped for 90
      single nucleotide polymorphisms (SNPs) in genes coding for proteins involved in
      the metabolism and transport of EFV, using a MassArray platform provided by
      Sequenom. The influence of these polymorphisms on EFV pharmacokinetics and the
      effects of demographic, clinical, biochemical, lifestyle, and concurrent drug
      covariates were evaluated. Plasma concentrations were fitted by a one-compartment
      model, with first-order absorption and elimination using nonlinear mixed-effect
      modeling (NONMEM program). The CYP2B6*6 allele, multidrug resistance-associated
      protein 4 (MRP4) 1497C -> T, and gamma-glutamyltranspeptidase (GGT) were
      identified as major factors influencing the apparent EFV oral clearance (CL/F),
      reducing the initial interindividual variability by 54.8%, according to the model
      CL/F = (12.2 - 0.00279 . GGT) . 0.602(CYP2B6*6 [G/T]) . 0.354(CYP2B6*6 [T/T]) .
      0.793(MRP4 1497C -> T), where CYP2B6*6 [G/T], CYP2B6*6 [T/T], and MRP4 1497C -> T
      take values of 0 or 1 to indicate the absence or presence of polymorphisms. The
      detailed genetic analysis conducted in this study identified two of 90 SNPs that
      significantly impacted CL/F, which might indicate that the remaining SNPs
      analyzed do not influence this PK parameter, at least in Caucasian populations
      with characteristics similar to those of our study population.

PMID- 21896913
TI  - Plasma and intracellular population pharmacokinetic analysis of tenofovir in HIV
      1-infected patients.
AB  - The relationships among the dose of tenofovir disoproxil fumarate (TDF),
      tenofovir (TFV) plasma concentrations, and intracellular TFV diphosphate (TFV-DP)
      concentrations are poorly understood. Our objective was to characterize TFV and
      TFV-DP relationships. Data were pooled from two studies in HIV-infected persons
      (n = 55) on stable antiretroviral therapy. TFV and TFV-DP were measured with
      validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) methods.
      Nonlinear mixed effects modeling (NONMEM 7) was used to develop the population
      model and explore the influence of covariates on TFV. A sequential analysis
      approach was utilized. A two-compartment model with first-order absorption best
      described TFV PK (FOCEI). An indirect stimulation of response model best
      described TFV-DP, where formation of TFV-DP was driven by plasma TFV
      concentration. Final plasma population estimates were as follows: absorption rate
      constant, 1.03 h(-1); apparent clearance (CL/F), 42 liters/h (33.5%
      interindividual variability [IIV]); intercompartment clearance, 181 liters/h;
      apparent central distribution volume (Vc/F), 273 liters (64.8% IIV); and apparent
      peripheral distribution volume (Vp/F), 440 liters (46.5% IIV). Creatinine
      clearance was the most significant covariate on CL/F and Vc/F. The correlation
      between CL/F and Vc/F was 0.553. The indirect response model for TFV-DP resulted
      in estimates of the maximal intracellular concentration (E(max)), the TFV
      concentration producing 50% of E(max) (EC(50)), and the intracellular elimination
      rate constant (k(out)) of 300 fmol/10(6) cells (82% IIV), 100 ng/ml (106% IIV),
      and 0.008 h(-1), respectively. The estimated k(out) gave an 87-h TFV-DP half
      life. A predictive check assessment indicated satisfactory model performance.
      This model links formation of TFV-DP with plasma TFV concentrations and should
      facilitate more informed investigations of TFV clinical pharmacology.

PMID- 21896911
TI  - Pharmacokinetics and safety of single-dose tenofovir disoproxil fumarate and
      emtricitabine in HIV-1-infected pregnant women and their infants.
AB  - Tenofovir (TFV) is effective in preventing simian immunodeficiency virus (SIV)
      transmission in a macaque model, is available as the oral agent tenofovir
      disoproxil fumarate (TDF), and may be useful in the prevention of mother-to-child
      transmission of human immunodeficiency virus (HIV). We conducted a trial of TDF
      and TDF-emtricitabine (FTC) in HIV-infected pregnant women and their infants.
      Women received a single dose of either 600 mg TDF, 900 mg TDF, or 900 mg TDF-600
      mg FTC at labor onset or prior to a cesarean section. Infants received no drug or
      a single dose of TDF at 4 mg/kg of body weight or of TDF at 4 mg/kg plus FTC at 3
      mg/kg as soon as possible after birth. All regimens were safe and well tolerated.
      Maternal areas under the serum concentration-time curve (AUC) and concentrations
      at the end of sampling after 24 h (C(24)) were similar between the two doses of
      TDF; the maximum concentrations of the drugs in serum (C(max)) and cord blood
      concentrations were higher in women delivering via cesarean section than in those
      who delivered vaginally (P = 0.04 and 0.046, respectively). The median ratio of
      the TFV concentration in cord blood to that in the maternal plasma at delivery
      was 0.73 (range, 0.26 to 1.95). Without TDF administration, infants had a median
      TFV concentration of 12 ng/ml 12 h after birth. Following administration of a
      single dose of TDF at 4 mg/kg, infant TFV concentrations fell below the targeted
      level, 50 ng/ml, by 24 h postdose. In HIV-infected pregnant women and their
      infants, 600 mg of TDF is acceptable as a single dose during labor. Low
      concentrations at birth support infant dosing as soon after birth as possible.
      Rapidly decreasing TFV levels in infants suggest that multiple or higher doses of
      TDF will be necessary to maintain concentrations that are effective for viral
      suppression.

PMID- 21896914
TI  - Inhibition of HIV-1 by octadecyloxyethyl esters of (S)-[3-hydroxy-2
      (phosphonomethoxy)propyl] nucleosides and evaluation of their mechanism of
      action.
AB  - (S)-1-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (HPMPC [cidofovir]) and (S)
      9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA) are potent inhibitors of
      a variety of DNA viruses. These drugs possess a 3'-hydroxyl equivalent which
      could support chain extension from an incorporated drug molecule. HPMPC and HPMPA
      were initially reported to lack activity against human immunodeficiency virus
      type 1 (HIV-1); more recent results have shown that the octadecyloxyethyl (ODE)
      and hexadecyloxypropyl (HDP) esters of HPMPA are potent inhibitors of the virus.
      We have synthesized the ODE esters of a series of (S)-[3-hydroxy-2
      (phosphonomethoxy)propyl] (HPMP) nucleosides, including HPMPC, HPMP-guanine
      (HPMPG), HPMP-thymine (HPMPT), and HPMP-diaminopurine (HPMPDAP), as well as the
      ODE ester of the obligate chain terminator (S)-9-[3-methoxy-2-(phosphonomethoxy)
      propyl]adenine (MPMPA). All compounds except ODE-HPMPT were inhibitors of HIV-1
      replication at low nanomolar concentrations. These compounds were also inhibitors
      of the replication of HIV-1 variants that are resistant to various nucleoside
      reverse transcriptase (RT) inhibitors at concentrations several times lower than
      would be expected to be achieved in vivo. To investigate the mechanism of the
      antiviral activity, the active metabolites of HPMPC and HPMPA were studied for
      their effects on reactions catalyzed by HIV-1 RT. Incorporation of HPMPC and
      HPMPA into a DNA primer strand resulted in multiple inhibitory effects exerted on
      the enzyme and showed that neither compound acts as an absolute chain terminator.
      Further, inhibition of HIV-1 RT also occurred when these drugs were located in
      the template strand. These results indicate that HPMPC and HPMPA inhibit HIV-1 by
      a complex mechanism and suggest that this class of drugs has a broader spectrum
      of activity than previously shown.

PMID- 21896915
TI  - Helicobacter pylori resistance to rifabutin in the last 7 years.
AB  - A low rate of resistance (0.24%) to rifabutin was noted in Helicobacter pylori
      strains isolated from 414 Japanese patients. The only rifabutin-resistant strain
      detected showed a point mutation in the rpoB gene and was isolated from a patient
      with a history of rifampin treatment for pulmonary tuberculosis.

PMID- 21896916
TI  - Increased pfmdr1 copy number and sequence polymorphisms in Plasmodium falciparum
      isolates from Sudanese malaria patients treated with artemether-lumefantrine.
AB  - Molecular markers for surveillance of Plasmodium falciparum resistance to current
      antimalarials are sorely needed. A 28-day efficacy study of artemether
      lumefantrine in eastern Sudan identified 5 treatment failures among 100 evaluable
      patients; 9 further individuals were parasite positive by PCR during follow-up.
      Polymorphisms in pfatpase6 and pfmdr1 were evaluated by DNA sequencing. One
      individual carried parasites with a novel pfmdr1 polymorphism (F1044L). pfmdr1
      gene amplification in parasites prior to treatment occurred in three individuals
      who had recurrent infection during follow-up.

PMID- 21896917
TI  - Not what you thought: how H+ ions combine with taurine or other aminosulfonates
      to close Cx26 channels.

PMID- 21896918
TI  - 5-Aminoimidazole-4-carboxyamide-ribonucleoside (AICAR)-stimulated hepatic
      expression of Cyp4a10, Cyp4a14, Cyp4a31, and other peroxisome proliferator
      activated receptor alpha-responsive mouse genes is AICAR 5'-monophosphate
      dependent and AMP-activated protein kinase-independent.
AB  - 5-Aminoimidazole-4-carboxyamide-ribonucleoside (AICAR), a prodrug activator of
      AMP-activated protein kinase (AMPK), increased hepatic expression of cytochrome
      P450 4a10, 4a14, and 4a31 mRNAs 2-, 3-, and 4-fold, respectively, and liver
      microsomal lauric acid omega-hydroxylation increased 2.8-fold. Likewise, mRNA
      levels of the peroxisome proliferator-activated receptor alpha (PPARalpha)
      responsive genes, Acox1, Acadm, Cpt1a, and Fabp1, were also increased by AICAR
      treatment. AICAR did not elicit these changes in PPARalpha null mice. In isolated
      murine hepatocytes, AICAR and adenosine produced similar effects, and these
      responses were blocked by the PPARalpha antagonist [(2S)-2-[[(1Z)-1-methyl-3-oxo
      3-[4-(trifluoromethyl)phenyl]-1-propenyl]amino]-3-[4-[2-(5-methyl-2-phenyl-4
      oxazolyl)ethoxy]phenyl]propyl]-carbamic acid ethyl ester (GW6471). Inhibition of
      AMPK using compound C (dorsomorphin or 6-[4-(2-piperidin-1-ylethoxy)phenyl]-3
      pyridin-4-ylpyrazolo[1,5-a]pyrimidine) did not block the induction of the
      PPARalpha-responsive genes by AICAR or adenosine, and 6,7-dihydro-4-hydroxy-3-(2'
      hydroxy[1,1'-biphenyl]-4-yl)-6-oxo-thieno[2,3-b]pyridine-5-carbonitrile (A
      769662), a non-nucleoside, direct activator of AMPK, did not increase expression
      of PPARalpha-responsive genes. An inhibitor of adenosine kinase, 5
      iodotubercidin, blocked these responses, suggesting that the phosphorylation of
      AICAR and adenosine to AICAR 5'-monophosphate (ZMP) or AMP, respectively, was
      required. Concentrations of ZMP and AMP were elevated and ATP levels diminished
      at 24 h. The PPARalpha-dependent responses were associated with increased
      concentrations of oleic acid, a potent PPARalpha agonist, and diminished levels
      of oleoyl-CoA. Oleoyl-CoA synthase activity was inhibited by ZMP and AMP with
      IC(50) values of 0.28 and 0.41 mM, respectively. These results suggest that
      PPARalpha is activated by increased concentrations of free fatty acids that may
      arise from impaired fatty acid metabolism caused by altered levels of ATP, AMP,
      and ZMP after AICAR or adenosine treatment.

PMID- 21896919
TI  - Heavy drinking and use of sedative or anxiolytic drugs among aging men: an 11
      year follow-up of the FinDrink study.
AB  - BACKGROUND: Most studies on heavy drinking and sedative/anxiolytic drug use have
      been cross-sectional, and evidence for a possible temporal association is
      lacking. OBJECTIVE: To prospectively investigate whether heavy drinking predicts
      initiation, continuation, or discontinuation of sedative/anxiolytic drugs at 4
      and 11 years and, conversely, whether sedative/anxiolytic drug use predicts heavy
      drinking. METHOD: This was a longitudinal population-based study conducted in
      Kuopio, Finland. An age-stratified random sample of 1516 men aged 42, 48, 54, and
      60 years received a structured clinical examination at baseline (August 1986
      December 1989). Follow-up clinical examinations were conducted at 4 (n = 1038)
      and 11 (n = 854) years. Multinomial logistic regression was used to compute odds
      ratios and 95% confidence intervals for the association between
      sedative/anxiolytic drug use and initiation, continuation, and discontinuation of
      heavy drinking (>= 14 drinks/wk). The reverse association between heavy drinking
      and sedative/anxiolytic drug use was also investigated. Regression models were
      adjusted for age, working status, smoking, and depressive symptoms. RESULTS: At
      baseline 12.9% (134/1038) of participants were heavy drinkers and 4.0% (41/1030)
      used sedative/anxiolytic drugs. In multivariate analyses, baseline heavy drinking
      predicted initiation of sedative/anxiolytic drug use at 4 years (OR 2.96; 95% CI
      1.23 to 7.15). Conversely, baseline sedative/anxiolytic drug use predicted
      continuation of heavy drinking at 11 years in unadjusted analysis (OR 3.30; 95%
      CI 1.19 to 8.44). However, the association was not statistically significant in
      adjusted analyses (OR 2.69; 95% CI 0.86 to 8.44). CONCLUSIONS: The main finding
      of this study was the association between heavy drinking and subsequent
      initiation of sedative/anxiolytic drugs that was not fully explained by baseline
      depressive symptoms. This may inform strategies to optimize the use of
      sedative/anxiolytic drugs, and assist in the early identification of patients at
      risk of heavy drinking. Clinicians should consider a patient's alcohol
      consumption prior to prescribing or dispensing sedative/anxiolytic drugs.
      Clinicians should also monitor patients prescribed sedative/anxiolytic drugs for
      subsequent heavy drinking.

PMID- 21896920
TI  - Evaluation of the accuracy of a pharmacokinetic dosing program in predicting
      serum vancomycin concentrations in critically ill patients.
AB  - BACKGROUND: Optimization of the timing of appropriate antibiotics is crucial to
      improve the management of patients in severe sepsis and septic shock. Vancomycin
      is commonly used empirically in cases of nosocomial infections in critically ill
      patients. Therefore, early optimization of vancomycin pharmacokinetics is likely
      to improve outcomes. OBJECTIVE: To evaluate a pharmacokinetic program to predict
      serum vancomycin concentrations in accordance with administered dose, weight,
      height, and creatinine clearance in a critically ill population. METHODS: We
      conducted a prospective observational single-center study in a 45-bed intensive
      care unit (ICU). All patients hospitalized in the ICU requiring intravenous
      treatment with vancomycin for a suspected infection were enrolled. The modalities
      of vancomycin therapy and the monitoring of serum concentrations were left to the
      discretion of the treating clinician. We compared the measured serum vancomycin
      concentrations with those predicted by the MM-USCPACK program and analyzed the
      factors influencing the prediction. RESULTS: Fifty-four intravenous vancomycin
      courses were administered in 48 critically ill patients over the 3-month study.
      The precision was considered acceptable, based on a relative precision equal to
      8.9% (interquartile range 3.5-18.9%) and the relative bias for all predictions
      was equal to -1.3%. Overall, 77.3% of predictions were within 20% of observed
      concentrations; factors correlating with a poorer prediction were a change in
      renal function, obesity, and the magnitude of organ dysfunction on initiation of
      vancomycin (expressed by a Systemic Organ Failure Assessment score >11).
      CONCLUSIONS: The MM-USCPACK program is a useful and reliable tool for prediction
      of serum vancomycin concentrations in patients hospitalized in ICU and likely
      reflects the close monitoring of renal function in this setting. For some
      patients (more severely ill, obese, or significant change in renal function
      during vancomycin therapy), predictions were less precise.

PMID- 21896923
TI  - Use of prasugrel in a patient with clopidogrel hypersensitivity.
AB  - OBJECTIVE: To report a case of successful use of prasugrel following percutaneous
      coronary intervention with placement of a bare metal stent in a patient with a
      documented hypersensitivity reaction to clopidogrel. CASE SUMMARY: A 61-year-old
      male with a history of coronary artery disease with coronary stent placement
      presented with ST-elevation myocardial infarction. The patient had developed
      Stephens-Johnson syndrome 6 years earlier following clopidogrel administration,
      characterized by erythematous plaques and subsequent desquamation of the hands
      and feet; clopidogrel was discontinued and he was subsequently treated with
      ticlopidine in addition to aspirin. The third-generation thienopyridine prasugrel
      was initiated as a therapeutic alternative to clopidogrel after placement of a
      bare metal stent; a 60-mg dose was administered after extubation, followed by 10
      mg/day. No signs of allergic reaction were observed in the days, weeks, and
      months following administration. DISCUSSION: Thienopyridines, specifically
      clopidogrel, are the standard of care for prevention of coronary stent
      thrombosis; however, there are few data available on cross-hypersensitivity
      between these agents. One study demonstrated that 27% of patients who developed
      an allergic or hematologic reaction to clopidogrel developed a similar reaction
      to ticlopidine. Other therapeutic options for patients with clopidogrel
      hypersensitivity who are undergoing a percutaneous coronary intervention with
      stent placement include clopidogrel desensitization, warfarin plus aspirin,
      cilostazol, ticagrelor, and ticlopidine. However, these options are limited by
      efficacy and/or toxicity. With its approval in 2009, prasugrel has become a
      potential treatment option. CONCLUSIONS: Prasugrel may be considered a
      therapeutic alternative in some patients allergic or intolerant to clopidogrel,
      but additional data are warranted to make a strong conclusion.

PMID- 21896924
TI  - Ofatumumab: a novel anti-CD20 monoclonal antibody for treatment of refractory
      chronic lymphocytic leukemia.
AB  - OBJECTIVE: To present the current clinical evidence on ofatumumab for use in
      refractory chronic lymphocytic leukemia (CLL). DATA SOURCES: A literature search
      was performed using MEDLINE and PubMed (both 1966-May 2011), as well as the
      American Society of Hematology abstracts (2000-May 2011), using the primary
      search terms ofatumumab and HuMax-CD20. STUDY SELECTION AND DATA EXTRACTION:
      Clinical studies and abstracts available in the English language, describing the
      pharmacology, pharmacokinetics, clinical activity, and safety of ofatumumab in
      CLL were included in this review. DATA SYNTHESIS: Ofatumumab is a human
      immunoglobulin monoclonal antibody that binds to B-lymphocytes expressing CD-20
      cell surface antigens. Ofatumumab was granted accelerated approval by the Food
      and Drug Administration in October 2009 for the treatment of CLL refractory to
      fludarabine and alemtuzumab. A Phase 1/2 trial has established the safety and
      tolerability of single-agent ofatumumab at an initial dose of 300 mg
      intravenously on week 1, followed by 2000 mg once weekly for 7 doses (weeks 2-8),
      followed by 2000 mg once every 4 weeks for 4 doses (weeks 9-12), for a total of
      12 doses. The final analysis of a pivotal international multicenter trial has
      shown promising activity in patients with CLL refractory to fludarabine and
      alemtuzumab, demonstrating overall response rates of 44-51%, with prolonged
      progression-free and overall survival. Ofatumumab activity has also been shown in
      a variety of other malignant and nonmalignant conditions, including non-Hodgkin
      lymphoma, rheumatoid arthritis, and multiple sclerosis. The most common adverse
      effect is grade 1 and 2 infusion reactions. Other adverse effects include
      infection, neutropenia, anemia, rash, fever, and diarrhea. CONCLUSIONS: Clinical
      evidence suggests that ofatumumab is an effective agent in patients with CLL
      refractory to fludarabine and alemtuzumab. Data are awaited comparing ofatumumab
      to other salvage regimens. Until results of head-to-head trials are conducted
      comparing ofatumumab to existing regimens, it cannot be said whether ofatumumab
      is more efficacious or tolerable than currently available therapies.

PMID- 21896927
TI  - C-peptide response and HLA genotypes in subjects with recent-onset type 1
      diabetes after immunotherapy with DiaPep277: an exploratory study.
AB  - OBJECTIVE: To investigate whether lower risk HLA class II genotypes would
      influence the efficacy of DiaPep277 therapy in protecting beta-cell function
      evaluated by C-peptide secretion in recent-onset type 1 diabetic subjects.
      RESEARCH DESIGN AND METHODS: Data were collected from type 1 diabetic subjects
      enrolled in multicenter phase II studies with a randomized, double-blind, and
      placebo-controlled design in whom fasting and stimulated C-peptide levels were
      measured. HLA genotypes were classified in high, moderate, and low risk
      categories. RESULTS: A total of 146 subjects (aged 4.3 to 58.5 years) were
      enrolled, including 76 children (<18 years old) and 70 adults. At baseline, there
      was a significant increase in fasting, maximal, and area under the curve (AUC) C
      peptide from high to moderate and low risk HLA genotypes in adults (P for trend
      <0.04) but not in children. Children showed a decrease of the three parameters
      over time regardless of therapy and HLA genotype. DiaPep277-treated adults with
      low risk genotype had significantly higher maximal and AUC C-peptide versus
      placebo at 12 months (0.04 +/- 0.07 vs. -0.28 +/- 0.09 nmol/L, P < 0.01, and 0.53
      +/- 1.3 vs. -4.59 +/- 1.5 nmol/L, P < 0.05, respectively). In the moderate risk
      genotype group, Deltamaximal and AUC C-peptide values were significantly higher
      in DiaPep277-treated versus placebo-treated patients (P < 0.01 and P < 0.05,
      respectively). CONCLUSIONS: This exploratory study demonstrates that type 1
      diabetic adults with low and moderate risk HLA genotypes benefit the most from
      intervention with DiaPep277; the only subgroup with an increase of C-peptide at
      12 months after diagnosis was the low risk DiaPep277-treated subgroup.

PMID- 21896928
TI  - Mediobasal hypothalamic SIRT1 is essential for resveratrol's effects on insulin
      action in rats.
AB  - OBJECTIVE: Sirtuin 1 (SIRT1) and its activator resveratrol are emerging as major
      regulators of metabolic processes. We investigate the site of resveratrol action
      on glucose metabolism and the contribution of SIRT1 to these effects. Because the
      arcuate nucleus in the mediobasal hypothalamus (MBH) plays a pivotal role in
      integrating peripheral metabolic responses to nutrients and hormones, we examined
      whether the actions of resveratrol are mediated at the MBH. RESEARCH DESIGN AND
      METHODS: Sprague Dawley (SD) male rats received acute central (MBH) or systemic
      injections of vehicle, resveratrol, or SIRT1 inhibitor during basal pancreatic
      insulin clamp studies. To delineate the pathway(s) by which MBH resveratrol
      modulates hepatic glucose production, we silenced hypothalamic SIRT1 expression
      using a short hairpin RNA (shRNA) inhibited the hypothalamic ATP-sensitive
      potassium (K(ATP)) channel with glibenclamide, or selectively transected the
      hepatic branch of the vagus nerve while infusing resveratrol centrally. RESULTS:
      Our studies show that marked improvement in insulin sensitivity can be elicited
      by acute administration of resveratrol to the MBH or during acute systemic
      administration. Selective inhibition of hypothalamic SIRT1 using a cell-permeable
      SIRT1 inhibitor or SIRT1-shRNA negated the effect of central and peripheral
      resveratrol on glucose production. Blockade of the K(ATP) channel and hepatic
      vagotomy significantly attenuated the effect of central resveratrol on hepatic
      glucose production. In addition, we found no evidence for hypothalamic AMPK
      activation after MBH resveratrol administration. CONCLUSIONS: Taken together,
      these studies demonstrate that resveratrol improves glucose homeostasis mainly
      through a central SIRT1-dependent pathway and that the MBH is a major site of
      resveratrol action.

PMID- 21896929
TI  - Role of lipid peroxidation and PPAR-delta in amplifying glucose-stimulated
      insulin secretion.
AB  - OBJECTIVE: Previous studies show that polyunsaturated fatty acids (PUFAs)
      increase the insulin secretory capacity of pancreatic beta-cells. We aimed at
      identifying PUFA-derived mediators and their cellular targets that are involved
      in the amplification of insulin release from beta-cells preexposed to high
      glucose levels. RESEARCH DESIGN AND METHODS: The content of fatty acids in
      phospholipids of INS-1E beta-cells was determined by lipidomics analysis. High
      performance liquid chromatography was used to identify peroxidation products in
      beta-cell cultures. Static and dynamic glucose-stimulated insulin secretion
      (GSIS) assays were performed on isolated rat islets and/or INS-1E cells. The
      function of peroxisome proliferator-activated receptor-delta (PPAR-delta) in
      regulating insulin secretion was investigated using pharmacological agents and
      gene expression manipulations. RESULTS: High glucose activated cPLA(2) and,
      subsequently, the hydrolysis of arachidonic and linoleic acid (AA and LA,
      respectively) from phospholipids in INS-1E cells. Glucose also increased the
      level of reactive oxygen species, which promoted the peroxidation of these PUFAs
      to generate 4-hydroxy-2E-nonenal (4-HNE). The latter mimicked the GSIS-amplifying
      effect of high glucose preexposure and of the PPAR-delta agonist GW501516 in INS
      1E cells and isolated rat islets. These effects were blocked with GSK0660, a
      selective PPAR-delta antagonist, and the antioxidant N-acetylcysteine or by
      silencing PPAR-delta expression. High glucose, 4-HNE, and GW501516 also induced
      luciferase expression in a PPAR-delta-mediated transactivation assay. Cytotoxic
      effects of 4-HNE were observed only above the physiologically effective
      concentration range. CONCLUSIONS: Elevated glucose levels augment the release of
      AA and LA from phospholipids and their peroxidation to 4-HNE in beta-cells. This
      molecule is an endogenous ligand for PPAR-delta, which amplifies insulin
      secretion in beta-cells.

PMID- 21896930
TI  - Deletion of the G6pc2 gene encoding the islet-specific glucose-6-phosphatase
      catalytic subunit-related protein does not affect the progression or incidence of
      type 1 diabetes in NOD/ShiLtJ mice.
AB  - OBJECTIVE: Islet-specific glucose-6-phosphatase catalytic subunit-related protein
      (IGRP), now known as G6PC2, is a major target of autoreactive T cells implicated
      in the pathogenesis of type 1 diabetes in both mice and humans. This study aimed
      to determine whether suppression of G6p2 gene expression might therefore prevent
      or delay disease progression. RESEARCH DESIGN AND METHODS: G6pc2(-/-) mice were
      generated on the NOD/ShiLtJ genetic background, and glycemia was monitored weekly
      up to 35 weeks of age to determine the onset and incidence of diabetes. The
      antigen specificity of CD8(+) T cells infiltrating islets from NOD/ShiLtJ
      G6pc2(+/+) and G6pc2(-/-) mice at 12 weeks was determined in parallel. RESULTS:
      The absence of G6pc2 did not affect the time of onset, incidence, or sex bias of
      type 1 diabetes in NOD/ShiLtJ mice. Insulitis was prominent in both groups, but
      whereas NOD/ShiLtJ G6pc2(+/+) islets contained CD8(+) T cells reactive to the
      G6pc2 NRP peptide, G6pc2 NRP-reactive T cells were absent in NOD/ShiLtJ G6pc2(-/
      ) islets. CONCLUSIONS: These results demonstrate that G6pc2 is an important
      driver for the selection and expansion of islet-reactive CD8(+) T cells
      infiltrating NOD/ShiLtJ islets. However, autoreactivity to G6pc2 is not essential
      for the emergence of autoimmune diabetes. The results remain consistent with
      previous studies indicating that insulin may be the primary autoimmune target, at
      least in NOD/ShiLtJ mice.

PMID- 21896931
TI  - Angiotensin II receptors modulate muscle microvascular and metabolic responses to
      insulin in vivo.
AB  - OBJECTIVE: Angiotensin (ANG) II interacts with insulin-signaling pathways to
      regulate insulin sensitivity. The type 1 (AT(1)R) and type 2 (AT(2)R) receptors
      reciprocally regulate basal perfusion of muscle microvasculature. Unopposed
      AT(2)R activity increases muscle microvascular blood volume (MBV) and glucose
      extraction, whereas unopposed AT(1)R activity decreases both. The current study
      examined whether ANG II receptors modulate muscle insulin delivery and
      sensitivity. RESEARCH DESIGN AND METHODS: Overnight-fasted rats were studied. In
      protocol 1, rats received a 2-h infusion of saline, insulin (3 mU/kg/min),
      insulin plus PD123319 (AT(2)R blocker), or insulin plus losartan (AT(1)R blocker,
      intravenously). Muscle MBV, microvascular flow velocity, and microvascular blood
      flow (MBF) were determined. In protocol 2, rats received (125)I-insulin with or
      without PD123319, and muscle insulin uptake was determined. RESULTS: Insulin
      significantly increased muscle MBV and MBF. AT(2)R blockade abolished insulin
      mediated increases in muscle MBV and MBF and decreased insulin-stimulated glucose
      disposal by ~30%. In contrast, losartan plus insulin increased muscle MBV by two-
      to threefold without further increasing insulin-stimulated glucose disposal.
      Plasma nitric oxide increased by >50% with insulin and insulin plus losartan but
      not with insulin plus PD123319. PD123319 markedly decreased muscle insulin uptake
      and insulin-stimulated Akt phosphorylation. CONCLUSIONS: We conclude that both
      AT(1)Rs and AT(2)Rs regulate insulin's microvascular and metabolic action in
      muscle. Although AT(1)R activity restrains muscle metabolic responses to insulin
      via decreased microvascular recruitment and insulin delivery, AT(2)R activity is
      required for normal microvascular responses to insulin. Thus, pharmacologic
      manipulation aimed at increasing the AT(2)R-to-AT(1)R activity ratio may afford
      the potential to improve muscle insulin sensitivity and glucose metabolism.

PMID- 21896932
TI  - Expansion of Th17 cells and functional defects in T regulatory cells are key
      features of the pancreatic lymph nodes in patients with type 1 diabetes.
AB  - OBJECTIVE: Autoimmune diseases, including type 1 diabetes, are thought to have a
      Th17-cell bias and/or a T-regulatory cell (Treg) defect. Understanding whether
      this is a hallmark of patients with type 1 diabetes is a crucial question that is
      still unsolved, largely due to the difficulties of accessing tissues targeted by
      the disease. RESEARCH DESIGN AND METHODS: We phenotypically and functionally
      characterized Th17 cells and Tregs residing in the pancreatic-draining lymph
      nodes (PLNs) of 19 patients with type 1 diabetes and 63 nondiabetic donors and
      those circulating in the peripheral blood of 14 type 1 diabetic patients and 11
      healthy subjects. RESULTS: We found upregulation of Th17 immunity and functional
      defects in CD4(+)CD25(bright) Tregs in the PLNs of type 1 diabetic subjects but
      not in their peripheral blood. In addition, the proinsulin-specific Treg-mediated
      control was altered in the PLNs of diabetic patients. The dysfunctional Tregs
      isolated from diabetic subjects did not contain contaminant effector T cells and
      were all epigenetically imprinted to be suppressive, as defined by analysis of
      the Treg-specific demethylated region within the forkhead box P3 (FOXP3) locus.
      CONCLUSIONS: These data provide evidence for an unbalanced immune status in the
      PLNs of type 1 diabetic subjects, and treatments restoring the immune homeostasis
      in the target organ of these patients represent a potential therapeutic strategy.

PMID- 21896934
TI  - Impact of resistance training on blood pressure and other cardiovascular risk
      factors: a meta-analysis of randomized, controlled trials.
AB  - We reviewed the effect of resistance training on blood pressure and other
      cardiovascular risk factors in adults. Randomized, controlled trials lasting >=4
      weeks investigating the effects of resistance training on blood pressure in
      healthy adults (age >=18 years) and published in a peer-reviewed journal up to
      June 2010 were included. Random- and fixed-effects models were used for analyses,
      with data reported as weighted means and 95% confidence limits. We included 28
      randomized, controlled trials, involving 33 study groups and 1012 participants.
      Overall, resistance training induced a significant blood pressure reduction in 28
      normotensive or prehypertensive study groups [-3.9 (-6.4; -1.2)/-3.9 (-5.6; -2.2)
      mm Hg], whereas the reduction [-4.1 (-0.63; +1.4)/-1.5 (-3.4; +0.40) mm Hg] was
      not significant for the 5 hypertensive study groups. When study groups were
      divided according to the mode of training, isometric handgrip training in 3
      groups resulted in a larger decrease in blood pressure [-13.5 (-16.5; -10.5)/
      6.1(-8.3; -3.9) mm Hg] than dynamic resistance training in 30 groups [-2.8 (-4.3;
      -1.3)/-2.7 (-3.8; -1.7) mm Hg]. After dynamic resistance training, Vo(2) peak
      increased by 10.6% (P=0.01), whereas body fat and plasma triglycerides decreased
      by 0.6% (P<0.01) and 0.11 mmol/L (P<0.05), respectively. No significant effect
      could be observed on other blood lipids and fasting blood glucose. This meta
      analysis supports the blood pressure-lowering potential of dynamic resistance
      training and isometric handgrip training. In addition, dynamic resistance
      training also favorably affects some other cardiovascular risk factors. Our
      results further suggest that isometric handgrip training may be more effective
      for reducing blood pressure than dynamic resistance training. However, given the
      small amount of isometric studies available, additional studies are warranted to
      confirm this finding.

PMID- 21896933
TI  - Genetic examination of SETD7 and SUV39H1/H2 methyltransferases and the risk of
      diabetes complications in patients with type 1 diabetes.
AB  - OBJECTIVE: Hyperglycemia plays a pivotal role in the development and progression
      of vascular complications, which are the major sources of morbidity and mortality
      in diabetes. Furthermore, these vascular complications often persist and progress
      despite improved glucose control, possibly as a result of prior episodes of
      hyperglycemia. Epigenetic modifications mediated by histone methyltransferases
      are associated with gene-activating events that promote enhanced expression of
      key proinflammatory molecules implicated in vascular injury. In this study, we
      investigated genetic polymorphisms of the SETD7, SUV39H1, and SUV39H2
      methyltransferases as predictors of risk for micro- and macrovascular
      complications in type 1 diabetes. RESEARCH DESIGN AND METHODS: In the Finnish
      Diabetic Nephropathy Study (FinnDiane) cohort, 37 tagging single nucleotide
      polymorphisms (SNPs) were genotyped in 2,991 individuals with type 1 diabetes and
      diabetic retinopathy, diabetic nephropathy, and cardiovascular disease. Seven
      SNPs were genotyped in the replication cohorts from the Steno Diabetes Center and
      All Ireland/Warren 3/Genetics of Kidneys in Diabetes (GoKinD) U.K. study.
      RESULTS: In a meta-analysis, the minor T allele of the exonic SNP rs17353856 in
      the SUV39H2 was associated with diabetic retinopathy (genotypic odds ratio 0.75,
      P = 1.2 * 10(-4)). The same SNP showed a trend toward an association with
      diabetic nephropathy as well as cardiovascular disease in the FinnDiane cohort.
      CONCLUSIONS: Our findings propose that a genetic variation in a gene coding for a
      histone methyltransferase is protective for a diabetic microvascular
      complication. The pathophysiological implications of this polymorphism or other
      genetic variation nearby for the vascular complications of type 1 diabetes remain
      to be investigated.

PMID- 21896935
TI  - Aortic stiffness and central wave reflections predict outcome in renal transplant
      recipients.
AB  - Although renal transplantation improves survival, cardiovascular morbidity and
      mortality remain significantly elevated compared with nonrenal populations. The
      negative impact of traditional, uremia-related, and transplantation-related risk
      factors in this process remains, however, largely unexplored. Surrogate markers
      such as aortic stiffness and central wave reflections may lead to more accurate
      cardiovascular risk stratification, but outcome data in renal transplant
      recipients are scarce. We aimed to establish the prognostic significance of these
      markers for fatal and nonfatal cardiovascular events in renal transplant
      recipients. Carotid-femoral pulse wave velocity, central augmentation pressure,
      and central augmentation index were measured in a cohort of 512 renal transplant
      recipients using the SphygmoCor system. After a mean follow-up of 5 years, 20
      fatal and 75 nonfatal cardiovascular events were recorded. Using receiver
      operating characteristic curves, the area under the curve for predicting
      cardiovascular events was 0.718 (95% CI 0.659-0.776) for pulse wave velocity,
      0.670 (95% CI 0.604-0.736) for central augmentation pressure, and 0.595 (95% CI
      0.529-0.660) for central augmentation index. When we accounted for age, gender,
      and C-reactive protein in Cox-regression analysis, pulse wave velocity (hazard
      ratio: 1.349 per 1 SD increase; 95% CI 1.104-1.649; P=0.003) and central
      augmentation pressure (hazard ratio: 1.487 per 1 SD increase; 95% CI 1.219-1.814;
      P<0.001) remained independent predictors of outcome. Aortic stiffness and
      increased wave reflections are independent predictors of cardiovascular events in
      renal transplant recipients. As single parameter of wave reflection, central
      augmentation pressure was better than central augmentation index. Combined
      measurement of pulse wave velocity and central augmentation pressure may
      contribute to an accurate cardiovascular risk estimation in this heterogeneous
      population.

PMID- 21896936
TI  - Exercise training alters the balance between vasoactive compounds in skeletal
      muscle of individuals with essential hypertension.
AB  - The effects of physical training on the formation of vasodilating and
      vasoconstricting compounds, as well as on related proteins important for vascular
      function, were examined in skeletal muscle of individuals with essential
      hypertension (n=10). Muscle microdialysis samples were obtained from subjects
      with hypertension before and after 16 weeks of physical training. Muscle
      dialysates were analyzed for thromboxane A(2), prostacyclin, nucleotides, and
      nitrite/nitrate. Protein levels of thromboxane synthase, prostacyclin synthase,
      cyclooxygenase 1 and 2, endothelial nitric oxide synthase (eNOS), cystathionine
      gamma-lyase, cytochrome P450 4A and 2C9, and the purinergic receptors P2X1 and
      P2Y2 were determined in skeletal muscle. The protein levels were compared with
      those of normotensive control subjects (n=12). Resting muscle dialysate
      thromboxane A(2) and prostacyclin concentrations were lower (P<0.05) after
      training compared with before training. Before training, dialysate thromboxane
      A(2) decreased with acute exercise, whereas after training, no changes were
      found. Before training, dialysate prostacyclin levels did not increase with acute
      exercise, whereas after training there was an 82% (P<0.05) increase from rest to
      exercise. The exercise-induced increase in ATP and ADP was markedly reduced after
      training (P<0.05). The amount of eNOS protein in the hypertensive subjects was
      40% lower (P<0.05) than in the normotensive control subjects, whereas
      cystathionine-gamma-lyase levels were 25% higher (P<0.05), potentially
      compensating for the lower eNOS level. We conclude that exercise training alters
      the balance between vasodilating and vasoconstricting compounds as evidenced by a
      decrease in the level of thromboxane, reduction in the exercise-induced increase
      in ATP and a greater exercise-induced increase in prostacyclin.

PMID- 21896937
TI  - Overexpression of the sodium chloride cotransporter is not sufficient to cause
      familial hyperkalemic hypertension.
AB  - The sodium chloride cotransporter (NCC) is the primary target of thiazides
      diuretics, drugs used commonly for long-term hypertension therapy. Thiazides also
      completely reverse the signs of familial hyperkalemic hypertension (FHHt),
      suggesting that the primary defect in FHHt is increased NCC activity. To test
      whether increased NCC abundance alone is sufficient to generate the FHHt
      phenotype, we generated NCC transgenic mice; surprisingly, these mice did not
      display an FHHt-like phenotype. Systolic blood pressures of NCC transgenic mice
      did not differ from those of wild-type mice, even after dietary salt loading. NCC
      transgenic mice also did not display hyperkalemia or hypercalciuria, even when
      challenged with dietary electrolyte manipulation. Administration of
      fludrocortisone to NCC transgenic mice, to stimulate NCC, resulted in an increase
      in systolic blood pressure equivalent to that of wild-type mice (approximately 20
      mm Hg). Although total NCC abundance was increased in the transgenic animals,
      phosphorylated (activated) NCC was not, suggesting that the defect in FHHt
      involves either activation of ion transport pathways other than NCC, or else
      direct activation of NCC, in addition to an increase in NCC abundance.

PMID- 21896939
TI  - Role of elevated heart rate in the development of cardiovascular disease in
      hypertension.

PMID- 21896942
TI  - N-Acetylcysteine Attenuates Fatigue Following Repeated-Bouts of Intermittent
      Exercise: Practical Implications for Tournament Situations.
AB  - Production of reactive oxygen species (ROS) during contractions is associated
      with muscular fatigue and damage in the short-term and adaptive responses in the
      long-term. When adaptation is inconsequential acute antioxidant supplementation
      may be able to attenuate muscle fatigue and damage to enhance performance. This
      study aimed to determine the effects of acute oral N-acetylcysteine (NAC)
      supplementation on Yo-Yo intermittent recovery test performance level one (YIRT
      L1) following repeated-bouts of damaging intermittent exercise. In a pair-matched
      design, twelve recreationally-trained males engaged in either six days of NAC (n
      = 6) or placebo (n = 6) supplementation. Following a treatment loading day,
      participants completed three testing sessions, on alternate days, consisting of a
      pre-exercise Isokinetic dynamometry (IKD) test, a damaging intermittent exercise
      protocol, YIRT-L1 and a post-exercise IKD. A further IKD test was completed on
      the two intervening days. NAC treatment resulted in a significant preservation of
      YIRT-L1 performance (P<=0.0005). IKD performance significantly deteriorated over
      time at all contractions speeds and this deterioration was not influenced by
      treatment group. Plasma creatine kinase values increased significantly over time
      (P=.002) and were significantly greater in the NAC group compared with the
      placebo group (P=.029). NAC induced mild-gastrointenstinal side effects. NAC
      supplementation may be a useful strategy to enhance performance during short-term
      competitive situations where adaption is inconsequential. Titration studies to
      elucidate a treatment dose that enhances performance without inducing side
      effects are now required.

PMID- 21896938
TI  - Silencing of hypoxia-inducible factor-1alpha gene attenuated angiotensin II
      induced renal injury in Sprague-Dawley rats.
AB  - Although it has been shown that upregulation of hypoxia-inducible factor (HIF)
      1alpha is protective in acute ischemic renal injury, long-term overactivation of
      HIF-1alpha is implicated to be injurious in chronic kidney diseases. Angiotensin
      II (Ang II) is a well-known pathogenic factor producing chronic renal injury and
      has also been shown to increase HIF-1alpha. However, the contribution of HIF
      1alpha to Ang II-induced renal injury has not been evidenced. The present study
      tested the hypothesis that HIF-1alpha mediates Ang II-induced renal injury in
      Sprague-Dawley rats. Chronic renal injury was induced by Ang II infusion (200
      ng/kg per minute) for 2 weeks in uninephrectomized rats. Transfection of vectors
      expressing HIF-1alpha small hairpin RNA into the kidneys knocked down HIF-1alpha
      gene expression by 70%, blocked Ang II-induced HIF-1alpha activation, and
      significantly attenuated Ang II-induced albuminuria, which was accompanied by
      inhibition of Ang II-induced vascular endothelial growth factor, a known
      glomerular permeability factor, in glomeruli. HIF-1alpha small hairpin RNA also
      significantly improved the glomerular morphological damage induced by Ang II.
      Furthermore, HIF-1alpha small hairpin RNA blocked Ang II-induced upregulation of
      collagen and alpha-smooth muscle actin in tubulointerstitial region. There was no
      difference in creatinine clearance and Ang II-induced increase in blood pressure.
      HIF-1alpha small hairpin RNA had no effect on Ang II-induced reduction in renal
      blood flow and hypoxia in the kidneys. These data suggested that overactivation
      of HIF-1alpha-mediated gene regulation in the kidney is a pathogenic pathway
      mediating Ang II-induced chronic renal injuries, and normalization of
      overactivated HIF-1alpha may be used as a treatment strategy for chronic kidney
      damages associated with excessive Ang II.

PMID- 21896944
TI  - Long-term effect of weight loss on body composition and performance in elite
      athletes.
AB  - CONTEXT: When weight loss (WL) is needed, it is recommended that athletes do it
      gradually by 0.5-1 kg/wk through moderate energy restriction. However, the effect
      of WL rate on long-term changes in body composition (BC) and performance has not
      been investigated in elite athletes. PURPOSE: To compare changes in body mass
      (BM), fat mass (FM), lean body mass (LBM), and performance 6 and 12 mo after 2
      different WL interventions promoting loss of 0.7% vs. 1.4% of body weight per wk
      in elite athletes. METHODS: Twenty-three athletes completed 6- and 12-mo
      postintervention testing (slow rate [SR] n = 14, 23.5 +/- 3.3 yr, 72.2 +/- 12.2
      kg; fast rate [FR] n = 9, 21.4 +/- 4.0 yr, 71.6 +/- 12.0 kg). The athletes had
      individualized diet plans promoting the predetermined weekly WL during
      intervention, and 4 strength-training sessions per wk were included. BM, BC, and
      strength (1-repetition maximum) were tested at baseline, postintervention, and 6
      and 12 mo after the intervention. RESULTS: BM decreased by ~6% in both groups
      during the intervention but was not different from baseline values after 12 mo.
      FM decreased in SR and FR during the intervention by 31% +/- 3% vs. 23% +/- 4%,
      respectively, but was not different from baseline after 12 mo. LBM and upper body
      strength increased more in SR than in FR (2.0% +/- 1.3% vs. 0.8% +/- 1.1% and 12%
      +/- 2% vs. 6% +/- 2%) during the intervention, but after 12 mo there were no
      significant differences between groups in BC or performance. CONCLUSION: There
      were no significant differences between groups after 12 mo, suggesting that WL
      rate is not the most important factor in maintaining BC and performance after WL
      in elite athletes.

PMID- 21896945
TI  - Trigonometric analysis of the mechanical axis deviation induced by telescopic
      intramedullary femoral lengthening nails.
AB  - Femoral lengthening with intramedullary nails can create alterations in the
      mechanical axis of the limb. This is based on the relationship of the anatomic
      femur axis to the mechanical femur axis, which is typically 5-9 degrees valgus.
      We developed trigonometric formulas to calculate the predicted change, using the
      lengths of the tibia, femur, and whole limb; the amount of lengthening; and the
      angle between the anatomic and the mechanical axis of the femur. We recognized
      three patterns depending on whether the overall limb mechanical axis is lateral
      (valgus), medial (varus), or straight through the center of the knee. The varus
      and valgus patterns lead to similar formulas. When the mechanical axis goes
      directly through the center of the knee joint, the formula simplifies. These
      formulas could be incorporated into digital radiographic programs to predict the
      change in mechanical axis deviation that will develop from lengthening along the
      anatomic femur axis with an intramedullary lengthening nail.

PMID- 21896946
TI  - Ski jumping takeoff in a wind tunnel with skis.
AB  - The effect of skis on the force-time characteristics of the simulated ski jumping
      takeoff was examined in a wind tunnel. Takeoff forces were recorded with a force
      plate installed under the tunnel floor. Signals from the front and rear parts of
      the force plate were collected separately to examine the anteroposterior balance
      of the jumpers during the takeoff. Two ski jumpers performed simulated takeoffs,
      first without skis in nonwind conditions and in various wind conditions.
      Thereafter, the same experiments were repeated with skis. The jumpers were able
      to perform very natural takeoff actions (similar to the actual takeoff) with skis
      in wind tunnel. According to the subjective feeling of the jumpers, the simulated
      ski jumping takeoff with skis was even easier to perform than the earlier trials
      without skis. Skis did not much influence the force levels produced during the
      takeoff but they still changed the force distribution under the feet.
      Contribution of the forces produced under the rear part of the feet was
      emphasized probably because the strong dorsiflexion is needed for lifting the
      skis to the proper flight position. The results presented in this experiment
      emphasize that research on ski jumping takeoff can be advanced by using wind
      tunnels.

PMID- 21896947
TI  - Three-dimensional model to predict muscle forces and their relation to motor
      variances in reaching arm movements.
AB  - A three-dimensional (3-D) arm movement model is presented to simulate kinematic
      properties and muscle forces in reaching arm movements. Healthy subjects
      performed reaching movements repetitively either with or without a load in the
      hand. Joint coordinates were measured. Muscle moment arms, 3-D angular
      acceleration, and moment of inertias of arm segments were calculated to determine
      3-D joint torques. Variances of hand position, arm configuration, and muscle
      activities were calculated. Ratios of movement variances observed in the two
      conditions (load versus without load) showed no differences for hand position and
      arm configuration variances. Virtual muscle force variances for all muscles
      except deltoid posterior and EMG variances for four muscles increased
      significantly by moving with the load. The greatly increased variances in muscle
      activity did not imply equally high increments in kinematic variances. We
      conclude that enhanced muscle cooperation through synergies helps to stabilize
      movement at the kinematic level when a load is added.

PMID- 21896948
TI  - Walking strategies during the transition between level and hill surfaces.
AB  - Healthy young adults transition between level and hill surfaces of various angles
      while walking at fluctuating speeds. These surface transitions have the potential
      to decrease dynamic balance in both the anterior-posterior and medial-lateral
      directions. Hence, the purpose of the current study was to analyze modifications
      in temporal-spatial parameters during hill walking transitions. We hypothesized
      that in comparison with level walking, the transition strides would indicate the
      adoption of a distinct gait strategy with a greater base of support. Thirty-four
      participants completed level and hill trials on a walkway with a 15-degree
      portable ramp apparatus. We collected data during 4 transition strides between
      level and ramp surfaces. In support of our hypothesis, compared with level
      walking, the base of support was 20% greater during 3 out of the 4 transition
      strides. In short, our results illustrate that healthy young adults did adopt a
      distinct gait strategy different from both level and hill walking during
      transitions strides.

PMID- 21896949
TI  - Evaluation of a subject-specific, torque-driven computer simulation model of one
      handed tennis backhand groundstrokes.
AB  - A torque-driven, subject-specific 3-D computer simulation model of the impact
      phase of one-handed tennis backhand strokes was evaluated by comparing
      performance and simulation results. Backhand strokes of an elite subject were
      recorded on an artificial tennis court. Over the 50-ms period after impact, good
      agreement was found with an overall RMS difference of 3.3 degrees  between
      matching simulation and performance in terms of joint and racket angles.
      Consistent with previous experimental research, the evaluation process showed
      that grip tightness and ball impact location are important factors that affect
      postimpact racket and arm kinematics. Associated with these factors, the model
      can be used for a better understanding of the eccentric contraction of the wrist
      extensors during one-handed backhand ground strokes, a hypothesized mechanism of
      tennis elbow.

PMID- 21896950
TI  - Morphological and mechanical properties of muscle and tendon in highly trained
      sprinters.
AB  - The purpose of this study was to investigate muscle and tendon properties in
      highly trained sprinters and their relations to running performance. Fifteen
      sprinters and 15 untrained subjects participated in this study. Muscle thickness
      and tendon stiffness of knee extensors and plantar flexors were measured.
      Sprinter muscle thickness was significantly greater than that of the untrained
      subjects for plantar flexors, but not for knee extensors (except for the medial
      side). Sprinter tendon stiffness was significantly lower than that of the
      untrained subjects for knee extensors, but not for plantar flexors. The best
      official record of a 100-m race was significantly correlated to the muscle
      thickness of the medial side for knee extensors. In conclusion, the tendon
      structures of highly trained sprinters are more compliant than those of untrained
      subjects for knee extensors, but not for plantar flexors. Furthermore, a thicker
      medial side of knee extensors was associated with greater sprinting performance.

PMID- 21896951
TI  - The effect of cerebrospinal fluid thickness on traumatic spinal cord deformation.
AB  - A spinal cord injury may lead to loss of motor and sensory function and even
      death. The biomechanics of the injury process have been found to be important to
      the neurological damage pattern, and some studies have found a protective effect
      of the cerebrospinal fluid (CSF). However, the effect of the CSF thickness on the
      cord deformation and, hence, the resulting injury has not been previously
      investigated. In this study, the effects of natural variability (in bovine) as
      well as the difference between bovine and human spinal canal dimensions on spinal
      cord deformation were studied using a previously validated computational model.
      Owing to the pronounced effect that the CSF thickness was found to have on the
      biomechanics of the cord deformation, it can be concluded that results from
      animal models may be affected by the disparities in the CSF layer thickness as
      well as by any difference in the biological responses they may have compared with
      those of humans.

PMID- 21896952
TI  - Varying treadmill speed and inclination affects spontaneous synchronization when
      two individuals walk side by side.
AB  - Studying spontaneous synchronization of stepping as two individuals walk on side
      by-side treadmills may be useful for understanding the control of bipedal
      locomotion and may have implications for gait rehabilitation. Existing data
      suggest that this behavior is related to differences in leg length, walkway
      slope, and overground speed between partners, and might be promoted by altering
      these variables. This idea was evaluated here as 24 pairs of subjects stepped on
      side-by-side treadmills under several conditions of relative speed and slope.
      Overall, pairings that demonstrated very little spontaneous synchronization with
      the same treadmill speed and slope exhibited significant increases in this
      behavior when one treadmill was manipulated. Conversely, pairings that
      demonstrated a tendency to synchronize under normal conditions exhibited
      significant decreases in this behavior when either treadmill was altered.

PMID- 21896953
TI  - Pedaling asymmetries in cyclists with unilateral transtibial amputation: effect
      of prosthetic foot stiffness.
AB  - Cyclists with unilateral transtibial amputation (CTA) provide a unique model to
      study integration of the neuromuscular and bicycle systems while having the
      option to modify this integration via the properties of the prosthesis. This
      study included eight CTA and nine intact cyclists. The cyclists pedaled on a
      stationary bicycle with instrumented force pedals. The CTA group pedaled with a
      stiff or flexible prosthetic foot during a simulated time trial and a low
      difficulty condition. During the time trial condition, pedaling with the flexible
      foot resulted in force and work asymmetries of 11.4% and 30.5%, the stiff foot
      displayed 11.1% and 21.7%, and the intact group displayed 4.3% and 4.2%,
      respectively. Similar trends were shown in the low difficulty condition. These
      data suggest foot stiffness has an effect on cycling symmetry in amputees.

PMID- 21896954
TI  - Dynamic optimization of the sit-to-stand movement.
AB  - The purpose of this study was to clarify criteria that can predict trajectories
      during the sit-to-stand movement. In particular, the minimum jerk and minimum
      torque-change models were examined. Three patterns of sit-to-stand movement from
      a chair, i.e., upright, natural, and leaning forward, were measured in five young
      participants using a 3-D motion analysis device (200 Hz). The trajectory of the
      center of mass and its smoothness were examined, and the optimal trajectories
      predicted by both models were evaluated. Trajectories of the center of mass
      predicted by the minimum torque-change model, rather than the minimum jerk model,
      resembled the measured movements in all rising movement patterns. The upright
      pattern required greater extension torque of the knee and ankle joints at the
      instant of seat-off. The leaning-forward pattern required greater extension hip
      torque and higher movement cost than the natural and upright patterns. These
      results indicate that the natural sit-to-stand movement might be a result of
      dynamic optimization.

PMID- 21896955
TI  - Influence of bicycle seat tube angle and hand position on lower extremity
      kinematics and neuromuscular control: implications for triathlon running
      performance.
AB  - We investigated how varying seat tube angle (STA) and hand position affect muscle
      kinematics and activation patterns during cycling in order to better understand
      how triathlon-specific bike geometries might mitigate the biomechanical
      challenges associated with the bike-to-run transition. Whole body motion and
      lower extremity muscle activities were recorded from 14 triathletes during a
      series of cycling and treadmill running trials. A total of nine cycling trials
      were conducted in three hand positions (aero, drops, hoods) and at three STAs (73
      degrees , 76 degrees , 79 degrees ). Participants also ran on a treadmill at 80,
      90, and 100% of their 10-km triathlon race pace. Compared with cycling, running
      necessitated significantly longer peak musculotendon lengths from the
      uniarticular hip flexors, knee extensors, ankle plantar flexors and the
      biarticular hamstrings, rectus femoris, and gastrocnemius muscles. Running also
      involved significantly longer periods of active muscle lengthening from the
      quadriceps and ankle plantar flexors. During cycling, increasing the STA alone
      had no affect on muscle kinematics but did induce significantly greater rectus
      femoris activity during the upstroke of the crank cycle. Increasing hip extension
      by varying the hand position induced an increase in hamstring muscle activity,
      and moved the operating lengths of the uniarticular hip flexor and extensor
      muscles slightly closer to those seen during running. These combined changes in
      muscle kinematics and coordination could potentially contribute to the improved
      running performances that have been previously observed immediately after cycling
      on a triathlon-specific bicycle.

PMID- 21896956
TI  - Flap irritation phenomenon (FLIP): etiology of chronic tenosynovitis after finger
      pulley rupture.
AB  - After a pulley rupture, most climbers regain the full function of their
      previously uninjured fingers. However, in some cases of pulley rupture, a
      persistent inflammation of the tendon sheath is observed. In this study, 16
      cadaver fingers were loaded until pulley rupture and then studied for the
      rupturing mechanism. In addition, two patients with this pathology were
      investigated using ultrasound and MRI, and received surgery. In 13 fingers, a
      rupture of one or several pulleys occurred and almost always at the medial or
      lateral insertion. In one finger, a capsizing of the pulley underneath the intact
      tendon sheath was observed, leading to an avulsion between tendon and tendon
      sheath. A similar pathology was observed in the ultrasound imaging, in MRI, and
      during surgery in two patients with prolonged recovery after minor pulley
      rupture. In cases of prolonged tenosynovitis after minor pulley rupture, a
      capsizing of the pulley stump is probably the cause for constant friction leading
      to inflammation. In those cases, a surgical removal of the remaining pulley stump
      and sometimes a pulley repair may be necessary.

PMID- 21896957
TI  - Effects of inversion perturbation after step down on the latency of the peroneus
      longus and peroneus brevis.
AB  - The purpose of this investigation was to determine the effect of different types
      of ankle sprains on the response latency of the peroneus longus and peroneus
      brevis to an inversion perturbation, as well as the time to complete the
      perturbation (time to maximum inversion). To create a forced inversion moment of
      the ankle, an outer sole with fulcrum was used to cause 25 degrees of inversion
      at the ankle upon landing from a 27 cm step-down task. Forty participants
      completed the study: 15 participants had no history of any ankle sprain, 15
      participants had a history of a lateral ankle sprain, and 10 participants had a
      history of a high ankle sprain. There was not a significant difference between
      the injury groups for the latency measurements or the time to maximum inversion.
      These findings indicate that a previous lateral ankle sprain or high ankle sprain
      does not affect the latency of the peroneal muscles or the time to complete the
      inversion range of motion.

PMID- 21896958
TI  - Global 5-hydroxymethylcytosine content is significantly reduced in tissue
      stem/progenitor cell compartments and in human cancers.
AB  - DNA methylation at the 5-position of cytosines (5 mC) represents an important
      epigenetic modification involved in tissue differentiation and is frequently
      altered in cancer. Recent evidence suggests that 5 mC can be converted to 5
      hydroxymethylcytosine (5 hmC) in an enzymatic process involving members of the
      TET protein family. Such 5 hmC modifications are known to be prevalent in DNA of
      embryonic stem cells and in the brain, but the distribution of 5 hmC in the
      majority of embryonic and adult tissues has not been rigorously explored. Here,
      we describe an immunohistochemical detection method for 5 hmC and the application
      of this technique to study the distribution of 5 hmC in a large set of mouse and
      human tissues. We found that 5 hmC was abundant in the majority of embryonic and
      adult tissues. Additionally, the level of 5 hmC closely tracked with the
      differentiation state of cells in hierarchically organized tissues. The highest 5
      hmC levels were observed in terminally differentiated cells, while less
      differentiated tissue stem/progenitor cell compartments had very low 5 hmC
      levels. Furthermore, 5 hmC levels were profoundly reduced in carcinoma of the
      prostate, breast and colon compared to normal tissues. Our findings suggest a
      distinct role for 5 hmC in tissue differentiation, and provide evidence for its
      large-scale loss in cancers.

PMID- 21896959
TI  - Mouse models to interrogate the implications of the differentiation status in the
      ontogeny of gliomas.
AB  - Glioblastoma multiforme (GBM) is the most common and lethal of human primary
      central nervous system (CNS) tumors, with a median survival of 14-16 months
      despite optimal surgery, radiation and chemotherapy. A reason for this dismal
      prognosis is insufficient understanding of the ontogeny of GBMs, which are highly
      heterogeneous at a pathological level. This pathological diversity, between and
      within GBMs as well as varying grades of gliomas, has not been fully explained
      solely on the grounds of oncogenic stimulus. Interaction with the tumor
      microenvironment is likely a source of this pathological heterogeneity, as well
      as the inherent characteristics of the tumor cell of origin. Currently,
      controversy exists on whether the initial transformed cell is a differentiated
      astrocyte, progenitor or neural stem cell. Putative cancer stem cells (CSCs),
      which have features of normal stem cell plus the ability to recapitulate the
      tumor phenotype in vivo in small numbers, have been identified from a variety of
      solid human cancers, including GBMs. Evidence suggesting that regions harboring
      normal stem cells in the adult CNS, such as the subventricular zone and the
      dentate gyrus, are more prone to viral and chemical oncogenesis, is supportive of
      the hypothesis that brain tumors arise from stem cells. However, it is still to
      be determined whether the appearance of brain tumor stem cells (BTSC) is the
      cause or consequence of tumor initiation and progression. This review discusses
      emerging evidence highlighting the relevance of the state of differentiation and
      regional heterogeneity in the ontogeny of GBM. This is an area of high interest
      in cancer in general, with potential significant therapeutic and prognostic
      implications.

PMID- 21896960
TI  - The NFkappaB pathway: a therapeutic target in glioblastoma.
AB  - Cancer initiating cells have been described to be the only cell population with
      tumorigenic capacity in glioblastoma multiforme, one of the most aggressive and
      untreatable cancers. Recent work from our group described that NFkappaB pathway
      was activated in glioblastoma initiating cells undergoing differentiation, and
      that blockade of this activation promoted senescence of differentiating cells.
      NFkappaB activation in cancer may be the result of either exposure to
      proinflammatory stimuli in the tumor microenvironment or upregulation of the
      signaling pathway by upstream regulators. Appropriate control of NFkappaB
      activity, which can be achieved by gene modification or pharmacological
      strategies, would provide a potential approach for the management of NFkappaB
      related tumors, including glioblastoma. Here, we summarize the current knowledge
      of the relevance of NFkappaB in cancer and its possible role as a target of
      therapeutic intervention..

PMID- 21896961
TI  - Signal and noise properties of position-sensitive avalanche photodiodes.
AB  - After many years of development, position-sensitive avalanche photodiodes
      (PSAPDs) are now being incorporated into a range of scintillation detector
      systems, including those used in high-resolution small-animal PET and PET/MR
      scanners. In this work, the signal, noise, signal-to-noise ratio (SNR), flood
      histogram and timing resolution were measured for lutetium oxyorthosilicate (LSO)
      scintillator arrays coupled to PSAPDs ranging in size from 10 to 20 mm, and the
      optimum bias voltage and working temperature were determined. Variations in the
      SNR performance of PSAPDs with the same dimensions were small, but the SNR
      decreased significantly with increasing PSAPD size and increasing temperature.
      Smaller PSAPDs (10 mm and 15 mm in width) produced acceptable flood histograms at
      24  degrees C, and cooling lower than 16  degrees C produced little improvement.
      The optimum bias voltage was about 25 V below the break down voltage. The larger
      20 mm PSAPDs have lower SNR and require cooling to 0-7  degrees C for acceptable
      performance. The optimum bias voltage is also lower (35 V or more below the break
      down voltage depending on the temperature). Significant changes in the timing
      resolution were observed as the bias voltage and temperature varied. Higher bias
      voltages provided better timing resolution. The best timing resolution obtained
      for individual crystals was 2.8 ns and 3.3 ns for the 10 mm and 15 mm PSAPDs,
      respectively. The results of this work provide useful guidance for selecting the
      bias voltage and working temperature for scintillation detectors that incorporate
      PSAPDs as the photodetector.

PMID- 21896962
TI  - Compressed sensing MRI with singular value decomposition-based sparsity basis.
AB  - Compressed sensing MRI (CS-MRI) aims to significantly reduce the measurements
      required for image reconstruction in order to accelerate the overall imaging
      speed. The sparsity of the MR images in transformation bases is one of the
      fundamental criteria for CS-MRI performance. Sparser representations can require
      fewer samples necessary for a successful reconstruction or achieve better
      reconstruction quality with a given number of samples. Generally, there are two
      kinds of 'sparsifying' transforms: predefined transforms and data-adaptive
      transforms. The predefined transforms, such as the discrete cosine transform,
      discrete wavelet transform and identity transform have usually been used to
      provide sufficiently sparse representations for limited types of MR images, in
      view of their isolation to the object images. In this paper, we present singular
      value decomposition (SVD) as the data-adaptive 'sparsity' basis, which can
      sparsify a broader range of MR images and perform effective image reconstruction.
      The performance of this method was evaluated for MR images with varying content
      (for example, brain images, angiograms, etc), in terms of image quality,
      reconstruction time, sparsity and data fidelity. Comparison with other commonly
      used sparsifying transforms shows that the proposed method can significantly
      accelerate the reconstruction process and still achieve better image quality,
      providing a simple and effective alternative solution in the CS-MRI framework.

PMID- 21896963
TI  - Approximations of noise covariance in multi-slice helical CT scans: impact on
      lung nodule size estimation.
AB  - Multi-slice computed tomography (MSCT) scanners have become popular volumetric
      imaging tools. Deterministic and random properties of the resulting CT scans have
      been studied in the literature. Due to the large number of voxels in the three
      dimensional (3D) volumetric dataset, full characterization of the noise
      covariance in MSCT scans is difficult to tackle. However, as usage of such
      datasets for quantitative disease diagnosis grows, so does the importance of
      understanding the noise properties because of their effect on the accuracy of the
      clinical outcome. The goal of this work is to study noise covariance in the
      helical MSCT volumetric dataset. We explore possible approximations to the noise
      covariance matrix with reduced degrees of freedom, including voxel-based
      variance, one-dimensional (1D) correlation, two-dimensional (2D) in-plane
      correlation and the noise power spectrum (NPS). We further examine the effect of
      various noise covariance models on the accuracy of a prewhitening matched filter
      nodule size estimation strategy. Our simulation results suggest that the 1D
      longitudinal, 2D in-plane and NPS prewhitening approaches can improve the
      performance of nodule size estimation algorithms. When taking into account
      computational costs in determining noise characterizations, the NPS model may be
      the most efficient approximation to the MSCT noise covariance matrix.

PMID- 21896964
TI  - Respiratory monitoring with an acceleration sensor.
AB  - Respiratory gating radiotherapy is used to irradiate a local area and to reduce
      normal tissue toxicity. There are certain methods for the detection of tumor
      motions, for example, using internal markers or an external respiration signal.
      However, because some of these respiratory monitoring systems require special or
      expensive equipment, respiratory monitoring can usually be performed only in
      limited facilities. In this study, the feasibility of using an acceleration
      sensor for respiratory monitoring was evaluated. The respiratory motion was
      represented by means of a platform and measured five times with the iPod touch(r)
      at 3, 4 and 5 s periods of five breathing cycles. For these three periods of the
      reference waveform, the absolute means +/- standard deviation (SD) of
      displacement were 0.45 +/- 0.34 mm, 0.33 +/- 0.24 mm and 0.31 +/- 0.23 mm,
      respectively. On the other hand, the corresponding absolute means +/- SD for the
      periods were 0.04 +/- 0.09 s, 0.04 +/- 0.02 s and 0.06 +/- 0.04 s. The accuracy
      of respiratory monitoring using the acceleration sensor was satisfactory in terms
      of the absolute means +/- SD. Using the iPod touch(r) for respiratory monitoring
      does not need special equipment and makes respiratory monitoring easier. For
      these reasons, this system is a viable alternative to other respiratory
      monitoring systems.

PMID- 21896965
TI  - Application of L1-norm regularization to epicardial potential reconstruction
      based on gradient projection.
AB  - The epicardial potential (EP)-targeted inverse problem of electrocardiography
      (ECG) has been widely investigated as it is demonstrated that EPs reflect
      underlying myocardial activity. It is a well-known ill-posed problem as small
      noises in input data may yield a highly unstable solution. Traditionally, L2-norm
      regularization methods have been proposed to solve this ill-posed problem. But
      the L2-norm penalty function inherently leads to considerable smoothing of the
      solution, which reduces the accuracy of distinguishing abnormalities and locating
      diseased regions. Directly using the L1-norm penalty function, however, may
      greatly increase computational complexity due to its non-differentiability. We
      propose an L1-norm regularization method in order to reduce the computational
      complexity and make rapid convergence possible. Variable splitting is employed to
      make the L1-norm penalty function differentiable based on the observation that
      both positive and negative potentials exist on the epicardial surface. Then, the
      inverse problem of ECG is further formulated as a bound-constrained quadratic
      problem, which can be efficiently solved by gradient projection in an iterative
      manner. Extensive experiments conducted on both synthetic data and real data
      demonstrate that the proposed method can handle both measurement noise and
      geometry noise and obtain more accurate results than previous L2- and L1-norm
      regularization methods, especially when the noises are large.

PMID- 21896966
TI  - Effect of the cortex on ultrasonic backscatter measurements of cancellous bone.
AB  - Ultrasonic backscatter techniques offer a promising new approach for detecting
      changes in bone caused by osteoporosis. However, several challenges impede
      clinical implementation of backscatter techniques. This study examines how the
      dense outer surface of bone (the cortex) affects backscatter measurements of
      interior regions of porous (cancellous) bone tissue. Fifty-two specimens of bone
      were prepared from 13 human femoral heads so that the same region of cancellous
      bone could be ultrasonically interrogated through the cortex or along directions
      that avoided the cortex. Backscatter signals were analyzed over a frequency range
      of 0.8-3.0 MHz to determine two ultrasonic parameters: apparent integrated
      backscatter (AIB) and frequency slope of apparent backscatter (FSAB). The term
      'apparent' means that the parameters are sensitive to the frequency-dependent
      effects of diffraction and attenuation. Significant (p < 0.001) changes in AIB
      and FSAB indicated that measurements through the cortex decreased the apparent
      backscattered power and increased the frequency dependence of the power. However,
      the cortex did not affect the correlation of AIB and FSAB with the x-ray bone
      mineral density of the specimens. This suggests that results from many previous
      in vitro backscatter studies of specimens of purely cancellous bone may be
      extrapolated with greater confidence to in vivo conditions.

PMID- 21896967
TI  - Simulation study on potential accuracy gains from dual energy CT tissue
      segmentation for low-energy brachytherapy Monte Carlo dose calculations.
AB  - This work compares Monte Carlo (MC) dose calculations for (125)I and (103)Pd low
      dose rate (LDR) brachytherapy sources performed in virtual phantoms containing a
      series of human soft tissues of interest for brachytherapy. The geometries are
      segmented (tissue type and density assignment) based on simulated single energy
      computed tomography (SECT) and dual energy (DECT) images, as well as the all
      water TG-43 approach. Accuracy is evaluated by comparison to a reference MC dose
      calculation performed in the same phantoms, where each voxel's material
      properties are assigned with exactly known values. The objective is to assess
      potential dose calculation accuracy gains from DECT. A CT imaging simulation
      package, ImaSim, is used to generate CT images of calibration and dose
      calculation phantoms at 80, 120, and 140 kVp. From the high and low energy images
      electron density rho(e) and atomic number Z are obtained using a DECT algorithm.
      Following a correction derived from scans of the calibration phantom, accuracy on
      Z and rho(e) of +/-1% is obtained for all soft tissues with atomic number Z ?
      [6,8] except lung. GEANT4 MC dose calculations based on DECT segmentation agreed
      with the reference within +/-4% for (103)Pd, the most sensitive source to tissue
      misassignments. SECT segmentation with three tissue bins as well as the TG-43
      approach showed inferior accuracy with errors of up to 20%. Using seven tissue
      bins in our SECT segmentation brought errors within +/-10% for (103)Pd. In
      general (125)I dose calculations showed higher accuracy than (103)Pd. Simulated
      image noise was found to decrease DECT accuracy by 3-4%. Our findings suggest
      that DECT-based segmentation yields improved accuracy when compared to SECT
      segmentation with seven tissue bins in LDR brachytherapy dose calculation for the
      specific case of our non-anthropomorphic phantom. The validity of our conclusions
      for clinical geometry as well as the importance of image noise in the tissue
      segmentation procedure deserves further experimental investigation.

PMID- 21896968
TI  - Automatic burst detection for the EEG of the preterm infant.
AB  - To aid with prognosis and stratification of clinical treatment for preterm
      infants, a method for automated detection of bursts, interburst-intervals (IBIs)
      and continuous patterns in the electroencephalogram (EEG) is developed. Results
      are evaluated for preterm infants with normal neurological follow-up at 2 years.
      The detection algorithm (MATLAB(r)) for burst, IBI and continuous pattern is
      based on selection by amplitude, time span, number of channels and numbers of
      active electrodes. Annotations of two neurophysiologists were used to determine
      threshold values. The training set consisted of EEG recordings of four preterm
      infants with postmenstrual age (PMA, gestational age + postnatal age) of 29-34
      weeks. Optimal threshold values were based on overall highest sensitivity. For
      evaluation, both observers verified detections in an independent dataset of four
      EEG recordings with comparable PMA. Algorithm performance was assessed by
      calculation of sensitivity and positive predictive value. The results of
      algorithm evaluation are as follows: sensitivity values of 90% +/- 6%, 80% +/- 9%
      and 97% +/- 5% for burst, IBI and continuous patterns, respectively.
      Corresponding positive predictive values were 88% +/- 8%, 96% +/- 3% and 85% +/-
      15%, respectively. In conclusion, the algorithm showed high sensitivity and
      positive predictive values for bursts, IBIs and continuous patterns in preterm
      EEG. Computer-assisted analysis of EEG may allow objective and reproducible
      analysis for clinical treatment.

PMID- 21896969
TI  - Advanced Poincare plot analysis differentiates between hypertensive pregnancy
      disorders.
AB  - Hypertensive pregnancy disorders affect 6% to 8% of all pregnancies and can
      result in severe complications for the mother and the foetus of which pre
      eclampsia (PE) has the worst perinatal outcome. Several studies suggested that
      the autonomic nervous system plays an important role in the process of developing
      hypertensive pregnancy disorders, especially PE. The aim of this retrospective
      study was to investigate whether women with PE could be differentiated from women
      with various other hypertensive pregnancy disorders, by employing an enhanced
      Poincare plot analysis (PPA), the segmented Poincare plot analysis (SPPA), to
      their beat-to-beat interval and blood pressure signals. Sixty-nine pregnant women
      with hypertensive disorders (29 PE, 40 with chronic or gestational hypertension)
      were included. The SPPA as well as the traditional PPA found significant
      differences between PE and other hypertensive disorders of diastolic blood
      pressure (p < 0.001 versus p < 0.001) but only the SPPA method revealed
      significant differences (p < 0.001) also of the systolic blood pressure. Further
      on, linear discrimination analysis demonstrated that indices derived from SPPA
      are more suitable for differentiation between chronic and gestational
      hypertension and PE than those from traditional PPA (area under the ROC curve
      0.85 versus 0.69). Therefore this procedure could contribute to the differential
      diagnosis of hypertensive pregnancy disorders.

PMID- 21896970
TI  - Smart sensor systems for human health breath monitoring applications.
AB  - Breath analysis techniques offer a potential revolution in health care
      diagnostics, especially if these techniques can be brought into standard use in
      the clinic and at home. The advent of microsensors combined with smart sensor
      system technology enables a new generation of sensor systems with significantly
      enhanced capabilities and minimal size, weight and power consumption. This paper
      discusses the microsensor/smart sensor system approach and provides a summary of
      efforts to migrate this technology into human health breath monitoring
      applications. First, the basic capability of this approach to measure exhaled
      breath associated with exercise physiology is demonstrated. Building from this
      foundation, the development of a system for a portable asthma home health care
      system is described. A solid-state nitric oxide (NO) sensor for asthma monitoring
      has been identified, and efforts are underway to miniaturize this NO sensor
      technology and integrate it into a smart sensor system. It is concluded that base
      platform microsensor technology combined with smart sensor systems can address
      the needs of a range of breath monitoring applications and enable new
      capabilities for healthcare.

PMID- 21896971
TI  - A selective nanosensor device for exhaled breath analysis.
AB  - This paper describes a novel concept of a three-nanosensor array microsystem that
      may potentially serve as a coarse diagnostic tool handheld breath analyzer to
      provide a first detection device. The specification and performance of a simple
      metal oxide nanosensor operating between three distinct temperatures are
      discussed, focusing on the need for a noninvasive blood cholesterol monitor.
      Interfacing the sensor array to an integrated circuit for electrical readout and
      temperature control provides a complete microsystem capable of capturing a single
      exhaled breath and analyzing it with respect to the relative content of isoprene,
      carbon dioxide and ammonia gas. This inexpensive sensor technology may be used as
      a personalized medical diagnostics tool in the near future.

PMID- 21896972
TI  - Breath analysis: clinical research to the end-user market.
AB  - Breath research is now well established and is solving some of the applications
      in the area of identifying volatiles for medical diagnosis. This paper looks at
      how this research has been taken to an end-user market. It is not intended to be
      an indepth study of the science but simply to draw attention to the role of the
      commercial link between the researcher and end-user. This market is not only in
      research but exists in hospitals, clinics, sports medicine and even homecare. The
      link between research and the end-user market is a vital one to avoid breath
      analysis being the tool of researchers only. The ubiquitous use of breath
      analysis depends upon it. This is a review of some of the success stories in
      commercializing the important breath analysis research that has been conducted
      over the last few decades. In order to make breath analysis the new blood test,
      products that have end-user appeal need to be developed and routes to market
      established.

PMID- 21896973
TI  - A microfabricated magnetic force transducer-microaspiration system for studying
      membrane mechanics.
AB  - The application of forces to cell membranes is a powerful method for studying
      membrane mechanics. To apply controlled dynamic forces on the piconewton scale,
      we designed and characterized a microfabricated magnetic force transducer (MMFT)
      consisting of current-carrying gold wires patterned on a sapphire substrate. The
      experimentally measured forces applied to paramagnetic and ferromagnetic beads as
      a function of applied current agree well with theoretical models. We used this
      device to pull tethers from microaspirated giant unilamellar vesicles and measure
      the threshold force for tether formation. In addition, the interlayer drag
      coefficient of the membrane was determined from the tether-return velocity under
      magnetic force-free conditions. At high levels of current, vesicles expanded as a
      result of local temperature changes. A finite element thermal model of the MMFT
      provided absolute temperature calibration, allowing determination of the thermal
      expansivity coefficient of stearoyl-oleoyl-phosphatidycholine vesicles (1.7 +/-
      0.4 * 10(-3) K(-1)) and characterization of the Joule heating associated with
      current passing through the device. This effect can be used as a sensitive probe
      of temperature changes on the microscale. These studies establish the MMFT as an
      effective tool for applying precise forces to membranes at controlled rates and
      quantitatively studying membrane mechanical and thermo-mechanical properties.

PMID- 21896975
TI  - A novel method to measure the generated voltage of a ZnO nanogenerator.
AB  - A novel method to measure the output voltage of a zinc oxide nanowire
      nanogenerator is proposed. Various tests are performed to verify that the output
      voltage does indeed originate from the nanogenerator and not from environmental
      noise. Although noise does influence the output voltage measurements, the output
      voltage is easily distinguishable from the measured noise. It is also shown that
      the method can be used to determine the internal resistance of the nanogenerator
      by measuring the output voltage over different output resistors.

PMID- 21896974
TI  - Wetting behavior and nanotribological properties of silicon nanopatterns combined
      with diamond-like carbon and perfluoropolyether films.
AB  - A large number of silicon (Si) patterns consisting of nanopillars of varying
      diameter and pitch have been fabricated and further coated with diamond-like
      carbon (DLC) and perfluoropolyether (Z-DOL) films. The wetting behavior and nano
      adhesion/friction of the patterns are investigated experimentally in relation to
      the nanostructures and the hydrophobicity of the materials. Measurements of water
      contact angle illustrate that the patterning-enhanced wettability of the Si flat
      surface, along with two distinct wettings which are in good agreement with the
      Wenzel and hemi-wicking states, depended on the value of the pitch-over-diameter
      ratio. In the case of the coated patterns, three wetting states are observed: the
      Cassie-Baxter, the Wenzel, and a transition from the Cassie-Baxter into the
      Wenzel, which varies with regard to the hydrophobic properties of the DLC and Z
      DOL. In terms of tribological properties, it is demonstrated that a combination
      of the nanopatterns and the films is effective in reducing adhesive and
      frictional forces. In addition, the pitch and diameter of the patterns are found
      to significantly influence their adhesion/friction behaviors.

PMID- 21896976
TI  - Catalytic characteristics of MnO2 nanostructures for the O2 reduction process.
AB  - Nanorods with an alpha type MnO(2) structure and a diameter ranging from 25 to 40
      nm, along with tipped needles with a beta MnO(2) structure and a diameter of 100
      nm were obtained. The 25 nm diameter alpha MnO(2) nanorods showed the best
      catalytic activity for dissociation of HO(2)(-) formed during oxygen reduction in
      a KOH solution. The MnO(2) nanostructures preferably followed a two-electron
      oxygen reduction mechanism in a LiOH solution. The size of the catalyst also
      affected the specific capacities of the non-aqueous Li/O(2) batteries fabricated
      using the MnO(2) based air electrode. The highest specific capacity of 1917 mA h
      g(-1) was obtained for an alpha MnO(2) nanorod catalyst having a diameter of 25
      nm. The cation present in the MnO(2) nanostructures appears to determine the
      catalytic activity of MnO(2).

PMID- 21896978
TI  - Multi-pulsed white light sintering of printed Cu nanoinks.
AB  - Pulse management of white light to maximize the sintering efficiency of a rapid
      (msec) and substrate-protective method, intense pulsed light (IPL), was studied
      systematically with a printable Cu nanoink. An excessive pulse energy that
      induces deleterious defects on the Cu film along with damage on a plastic
      substrate was dissipated into multiple sub-pulses while maintaining a total
      energy budget over the threshold level for successful Cu sintering. Electrical
      properties of the metal layers were analyzed in conjunction with pulse formation
      factors such as average energy, pulse duration, peak power and pulse number to
      determine their respective effects on IPL sintering. In the quantitative results,
      the optimized sintering conditions of copper nanoparticles with a mean diameter
      of 30 nm and a fixed total irradiated pulse energy of 32 J cm(-2) were a pulse
      number and pulse width of > 4 and < 3 msec, respectively.

PMID- 21896977
TI  - Biocompatible transferrin-conjugated sodium hexametaphosphate-stabilized gold
      nanoparticles: synthesis, characterization, cytotoxicity and cellular uptake.
AB  - The feasibility of using gold nanoparticles (AuNPs) for biomedical applications
      has led to considerable interest in the development of novel synthetic protocols
      and surface modification strategies for AuNPs to produce biocompatible molecular
      probes. This investigation is, to our knowledge, the first to elucidate the
      synthesis and characterization of sodium hexametaphosphate (HMP)-stabilized gold
      nanoparticles (Au-HMP) in an aqueous medium. The role of HMP, a food additive, as
      a polymeric stabilizing and protecting agent for AuNPs is elucidated. The surface
      modification of Au-HMP nanoparticles was carried out using polyethylene glycol
      and transferrin to produce molecular probes for possible clinical applications.
      In vitro cell viability studies performed using as-synthesized Au-HMP
      nanoparticles and their surface-modified counterparts reveal the biocompatibility
      of the nanoparticles. The transferrin-conjugated nanoparticles have significantly
      higher cellular uptake in J5 cells (liver cancer cells) than control cells (oral
      mucosa fibroblast cells), as determined by inductively coupled plasma mass
      spectrometry. This study demonstrates the possibility of using an inexpensive and
      non-toxic food additive, HMP, as a stabilizer in the large-scale generation of
      biocompatible and monodispersed AuNPs, which may have future diagnostic and
      therapeutic applications.

PMID- 21896979
TI  - Carbon nanowalls amplify the surface-enhanced Raman scattering from Ag
      nanoparticles.
AB  - We report surface-enhanced Raman scattering (SERS) from Ag nanoparticles
      decorated on thin carbon nanowalls (CNWs) grown by microwave plasma chemical
      vapor deposition. The Ag morphology is controlled by exposing the CNWs to oxygen
      plasma and through the electrodeposition process by varying the number of
      deposition cycles. The SERS substrates are capable of detecting low
      concentrations of rhodamine 6G and bovine serum albumin, showing much higher
      Raman enhancement than ordinary planar HOPG with Ag decoration. The major factors
      contributing to this behavior include: high density of Ag nanoparticles, large
      surface area, high surface roughness, and the underlying presence of vertically
      oriented CNWs. The relatively simple procedure of substrate preparation and
      nanoparticle decoration suggests that this is a promising approach for
      fabricating ultrasensitive SERS substrates for biological and chemical detection
      at the single-molecule level, while also enabling the study of fundamental SERS
      phenomena.

PMID- 21896980
TI  - A nanowire-based shift register for display scan drivers.
AB  - The development of display scan drivers is an essential step in the effort to
      develop transparent and flexible display devices based on nanowire transistors.
      Here we report a transparent nanowire-based shift register that functions as the
      standard logic circuit of a display scan driver. To form the shift register
      circuits using only n-type nanowire transistors, a novel circuit structure was
      introduced to avoid the output voltage drop typical of purely n-type circuits. A
      circuit simulation based on the measured nanowire transistor characteristics was
      developed in the planning phase to verify the circuit operation of the shift
      register. The shift register successfully produced an output of 0-3 V without an
      output voltage drop while applying an input of 3 V peak to peak. In addition, the
      shift register was designed to have multiple channels with a randomly oriented
      nanowire placement method to enhance the operation yield.

PMID- 21896981
TI  - Cytoprotective properties of a fullerene derivative against copper.
AB  - To delineate the complexity of the response of cells to nanoparticles we have
      performed a study on HT-29 human colon carcinoma cells exposed first to a
      fullerene derivative C(60)(OH)(20) and then to physiological copper ions. Our
      cell viability, proliferation, and intracellular reactive oxygen species (ROS)
      production assays clearly indicated that C(60)(OH)(20) suppressed cell damage as
      well as ROS production induced by copper, probably through neutralization of the
      metal ions by C(60)(OH)(20) in the extracellular space, as well as by adsorption
      and uptake of the nanoparticles surface-modified by the biomolecular species in
      the cell medium. This double-exposure study provides new data on the effects of
      nanoparticles on cell metabolism and may aid the treatment of oxidant-mediated
      diseases using nanomedicine.

PMID- 21896982
TI  - Mechanical properties of grafold: a demonstration of strengthened graphene.
AB  - Morphological patterns and structural features play crucial roles in the physical
      properties of functional materials. In this paper, the mechanical properties of
      grafold, an architecture of folded graphene nanoribbon, are investigated via
      molecular dynamics simulations and intriguing features are discovered. In
      contrast to graphene, grafold is found to develop large deformations upon both
      tensile and compressive loading along the longitudinal direction. The tensile
      deformation is plastic, whereas the compressive deformation is elastic and
      reversible within the strain range investigated. The calculated Young's modulus,
      tensile strength, and fracture strain are comparable to those of graphene, while
      the compressive strength and strain are much higher than those of graphene. The
      length, width, and folding number of grafold have distinctive impacts on the
      mechanical performance. These unique behaviors render grafold a promising
      material for advanced mechanical applications.

PMID- 21896983
TI  - Photo-induced suppression of plasmonic emission enhancement of CdSe/ZnS quantum
      dots.
AB  - Emission of semiconductor quantum dots can be increased via two fundamentally
      different processes: (i) surface plasmon resonances (plasmonic emission
      enhancement) and (ii) irradiation with light (photo-induced fluorescence
      enhancement). In this paper we theoretically and experimentally study the mutual
      impacts of these processes on each other in quantum dot solids. We show that when
      thin films of colloidal quantum dots are placed in the vicinity of Au nano
      islands, the plasmonic enhancement of the radiative decay rates of quantum dots
      and Forster energy transfer can hinder the photo-induced fluorescence enhancement
      of these films. This in turn leads to significant suppression of their plasmonic
      emission enhancement when they are irradiated with a laser beam. We investigate
      the impact of the sizes and shapes of the metallic nanoparticles in this process
      and theoretically analyze how plasmons and energy transfer can hinder the
      electrostatic barrier responsible for photo-induced fluorescence enhancement.

PMID- 21896984
TI  - Construction of high-quality CdS:Ga nanoribbon/silicon heterojunctions and their
      nano-optoelectronic applications.
AB  - Silicon based optoelectronic integration is restricted by its poor optoelectronic
      properties arising from the indirect band structure. Here, by combining silicon
      with another promising optoelectronic material, the CdS nanoribbon (NR), devices
      with heterojunction structure were constructed. The CdS NRs were also doped with
      gallium to improve their n-type conductivity. A host of nano-optoelectronic
      devices, including light emitting diodes, photovoltaic devices, and
      photodetectors, were successfully constructed on the basis of the CdS:Ga NR/Si
      heterojunctions. They all exhibited excellent device performances as regards high
      stability, high efficiency, and fast response speed. It is expected that the CdS
      NR/Si heterojunctions will have great potential for future applications of Si
      based optoelectronic integration.

PMID- 21896985
TI  - Expression of hypoxia inducible factor-1 alpha in matched hormone naive and
      castrate resistant prostate cancer specimens.
AB  - Hypoxia inducible factor-1 alpha (HIF-1alpha) is known as an important
      transcription factor in endocrine tumours. It is elevated in hypoxic tumour
      microenvironment, increasing angiogenesis and enabling tumour cells to enter the
      circulation. We therefore hypothesised that patients with advanced prostate
      cancer disease have high tumoural HIF-1alpha xpression and worse disease specific
      survival. Aim of this study was to assess expression of HIF-1alpha in prostate
      cancer specimens taken before and after castrate resistance to address its
      cellular location and to examine if this is associated with clinicopathological
      features and clinical outcome of the particular prostate cancer cohort. 50 pairs
      of hormone naive and castrate resistant prostate cancer specimens were analysed
      employing tissue microarray technology. Immunohistochemistry was performed using
      an antibody to HIF-1alpha.HIF-1alpha expression was observed in both, cytoplasm
      and nucleus. Cytoplasmic HIF-1alpha expression correlated positively with
      metastases at diagnosis (p=0.005), whereas nuclear HIF-1alpha expression
      correlated with metastases at relapse (p=0.041). Cytoplasmic and nuclear HIF
      1alpha expression did not change from hormone naive to hormone castrate resistant
      tumours. No significant association was observed in this study between tumoural
      HIF-1alpha expression, biochemical relapse and patient survival. HIF-1alpha was
      associated with the presence of metastases at time of diagnosis and time of
      relapse. HIF-1alpha is likely to play a role in progressive prostate cancer.

PMID- 21896986
TI  - Recurrent amplification in the 22q11 region in laryngeal squamous cell carcinoma
      results in overexpression of the CRKL but not the MAPK1 oncogene.
AB  - Thirteen laryngeal squamous cell carcinoma cell lines were recently studied by
      array comparative genomic hybridization (array-CGH) in order to identify
      recurrent DNA copy number alterations in the tumor genome. A highly amplified
      region 22q11.2 was found in two of the thirteen cell lines. Two established
      oncogenes CRKL and MAPK1 are localized in this region, but only CRKL was
      amplified in both cell lines. Therefore, to check if amplification of either CRKL
      or MAPK1 genes may be important in the pathogenesis of laryngeal squamous cell
      carcinoma, the DNA copy number and mRNA expression were measured in a cohort of
      17 LSCC cell lines by quantitative real-time PCR (qPCR). For the CRKL gene gains
      of the copy number were found in 3/17 cell lines, while overexpression was found
      in 6/17 cell lines. Gains in the copy number for the MAPK1 gene were found in
      1/17 cell lines, but overexpression was not detected in any cell line. A highly
      significant correlation between DNA copy number and expression for CRKL gene, but
      not for MAPK1 gene was established using the Pearson test. Thereafter, 46 primary
      samples of laryngeal cancer were tested by qPCR to check for possible gains in
      copy number of the CRKL gene. Gains were found in 3/46 cases. These results
      suggest that CRKL, but not MAPK1 is the target oncogene of the rare but recurrent
      amplification at 22q11.2 in laryngeal squamous cell carcinoma.

PMID- 21896987
TI  - Role of p53 gene polymorphism and bladder cancer predisposition in northern
      India.
AB  - p53 is a major orchestrator of cellular response to a broad array of stress types
      by regulating apoptosis, cell cycle arrest, etc. A few polymorphic sites, one at
      codon72 of exon4, intron3 16bpdel/ins, intron6G>A have been studied with regard
      to Bladder cancer (BC) risk in North Indians. Genotypes were assessed in hospital
      based case-control study comprising of 200BC cases, 265healthy controls. After
      extraction of genomic DNA from blood, genotyping was done using PCR Restriction
      Fragment Length Polymorphism. Individuals with p53R72P G>C, CC genotype
      demonstrated marginally reduced risk of BC (p=0.053, OR=0.29, 95% 16bp-ins/del.

PMID- 21896988
TI  - A CYP17A1 gene polymorphism in association with multiple uterine leimyomas; a
      meta-analysis.
AB  - OBJECTIVE: The mutant genotype GG of the CYP17A1 gene polymorphism has been
      linked to higher levels of serum estradiol and thus might be associated with
      steroid-hormone dependent tumors. We decided to assess an association of CYP17A1
      polymorphism with uterine leiomyomas (ULM) and multiple ULM by conducting a meta
      analysis and subgroup analysis. METHODS: We searched the HuGE Navigator and
      PubMed databases using the terms "leiomyoma" and "CYP17A1" for articles published
      by October 1, 2010. Our article in press was added. The selection criteria were
      (i) cases having ULM, (ii) controls showing no ULM from the same ethnic group,
      (iii) cases and controls not overlapping. The subgroup analysis included cases
      having multiple ULM, predisposing black women mostly present with multiple ULM.
      Pooled risk ratio was calculated using chi<formula> ^{2}</formula> statistic.
      RESULTS: Five papers fulfilled the selection criteria for meta-analysis and two
      papers for the subgroup analysis. The meta-analysis revealed no association of
      CYP17A1 polymorphism with all ULM. A high pooled risk ratio for multiple ULM was
      associated with the presence of mutant genotype GG (RR 3.25). CONCLUSION: CYP17A1
      polymorphism may be associated with multiple ULM but not with all ULM. The future
      research might enable us to predict the course of the disease.

PMID- 21896989
TI  - WT1 expression as an independent marker of poor prognosis in colorectal cancers.
AB  - WT1 has been proven to be a prognostic marker and molecular target in various
      human cancers. In this study, we aimed to investigate the prognostic role of WT1
      in colorectal cancers (CRCs). Archival tissue samples from 157 CRC cases who
      underwent curative surgery in our institute from February 1999 to May 2004 were
      subjected to WT1 expression studies using an immunohistochemistry technique.
      Number of positive staining per 500 tumor cells and staining intensities were
      analyzed against overall survival. Of 157 CRCs, 83 were colonic and 74 were
      rectal cancers. The mean follow-up period was 116 (range 77-145) months. Five
      year and seven-year OS rates were 60.9% and 52.8%, respectively. WT1
      immunostaining was positive in 143 cases (91%). The median number of positive
      cells was 120 (range 0-420). Univariate analysis by Log-rank test showed that
      AJCC stage, tumor site (rectal cancer), number of positive cells > 120 and high
      staining intensity (score ++/+++) were significantly associated with poorer
      survival (p-value < 0.01). Five-year survival rates in cases with positive cells
      of ? 120 cells and > 120 cells were 72.2% and 49.4%, respectively. Five-year
      survival in cases with staining intensity of ++ or more was 45.3%, compared with
      69% in cases with intensity of less than ++. Multivariate regression analysis
      demonstrated that the staining intensity, high tumor stage and rectal site were
      independent factors indicating poorer survival. Our findings indicate that WT1
      expression is a marker of poor prognosis in CRCs, independent of AJCC staging.

PMID- 21896991
TI  - MDM2 amplification is an independent prognostic feature of node-negative,
      estrogen receptor-positive early-stage breast cancer.
AB  - BACKGROUND: MDM2 is overexpressed and amplified in a number of malignant tumors
      including breast carcinomas. Cell culture experiments showed a close connection
      between %of MDM2 expression and estrogen receptor status in breast cancer cell
      lines. Only little is known about the role of MDM2 amplifications in early-stage
      breast carcinomas with positive estrogen receptor status. METHODS: 661 highly
      characterized node-negative breast carcinomas with positive estrogen receptor
      status (ER+ early-stage breast carcinomas) were analyzed on a tissue microarray.
      Molecular (HER2, CCND1, MDM2, MYC, 8q21), as well as estrogen receptor expression
      data used in this analysis, was available from previously published studies. The
      primary endpoint of overall survival analysis was death after 10 years. RESULTS:
      Gene amplifications were found in 194/661 (29%) ER+ early-stage breast carcinomas
      and 40 (7%) exhibited amplification of the MDM2 oncogene. MDM2 amplifications
      were significantly related to advanced tumor stage (p < 0.05) and high Ki67
      expression levels (p < 0.05). There was no relationship between MDM2 copy number
      changes and tumor grade, estrogen receptor expression level and co-amplification
      of HER2, CCND1 and 8q. Tumor stage (pT1 vs pT2-pT4; HR 1.51; 95% CI 1.02-2.24;
      p=0.042), grading (G1-G2 vs G3; HR 2.27; 95% CI 1.51-3.43; p < 0.001), high Ki67
      proliferation index (HR 2.03; 95% CI 1.31-3.15; p=0.0015), HER2 (HR 2.6; 95% CI
      1.51 to 4.5; p < 0.001) and MDM2 amplification (HR 2.05, 95% CI 1.06-3.97, p
      =0.033) were statistically adverse prognostic risk factors in univariate Cox
      regression analysis. Patient age, estrogen receptor expression level, CCND1 and
      8q amplification were not associated to overall survival. Multivariate Cox
      regression analysis of survival data included tumor stage, grading, Ki67 labeling
      index, HER2 and MDM2 amplification status. In this statistical model, only MDM2
      amplification was an independent factor for overall patient survival in ER+ early
      stage breast carcinomas (HR 2.64; 95% CI 1.32 to 5.28; p=0.006). CONCLUSION: The
      MDM2 oncogene is amplified in a substantial proportion of ER+ early-stage breast
      carcinomas and an independent parameter for poor patient outcome in this
      subgroup. The prognostic effect of MDM2 is closely connected to estrogen receptor
      expression of breast carcinomas.

PMID- 21896990
TI  - Genetic investigation of FOXE1 polyalanine tract in thyroid diseases: new insight
      on the role of FOXE1 in thyroid carcinoma.
AB  - FOXE1 polyalanine tract (poly-Ala) has been associated with thyroid dysgenesis.
      Recently, the SNP (rs1867277:-238G>A) within the FOXE1 5'UTR was involved in the
      genetic susceptibility to thyroid cancer (TC). In the aim to assess the influence
      of FOXE1 poly-Ala length on the genetic susceptibility to TC and autoimmune
      thyroid diseases (AITD), a case-control design (including 261 Tunisian AITD, 170
      Spanish TC and respectively 171 and 218 matched healthy subjects) was performed.
      The effect of Ala length and rs1867277 alleles on FOXE1 expression was
      investigated by mRNA relative real time quantification on 8 papillary thyroid
      carcinoma (PTC) and 10 Graves' disease (GD) genotyped thyroid biopsies. The
      fluorescent genotyping of poly-Ala polymorphism revealed nine alleles (from 12 to
      22 repetitions). The association of poly-Ala polymorphism with AITD was rejected
      (Pc>0.05). However, a significant association was found with TC. In addition, the
      genotypic distributions revealed the predispositional effect of the 16/16
      genotype (OR = 2.71; 95%CI: 1.36-5.42; p=0.001) and the protector effect of the
      14/14 genotype (OR= 0.46; 95%CI: 0.29-0.72; p=0.003). The quantification studies
      reveal that FOXE1 transcripts were less abundant in PTC than GD samples.
      Moreover, FOXEI gene was 4,8 fold less expressed among PTC protected patients
      compared to homozygous 16/16-A/A. In conclusion, by exploring the poly-Ala
      polymorphism, we confirmed the involvement of {?it FOXE1} gene in the genetic
      susceptibility to TC and we reported its down expression among PTC tissues.

PMID- 21896992
TI  - The EGFR R521K polymorphism influences the risk to develop colorectal cancer.
AB  - Epidermal growth factor receptor (EGFR) family members (EGFR, HER2, HER3 and
      HER4) have been extensively investigated for its possible involvement in cancer
      development and progression. In colorectal cancer (CRC) EGFR family has been
      found frequently over-expressed, thus therapy targeting EGFR has been developed.
      Interestingly, it has been observed that genetic variants in these receptors may
      alter the therapeutic efficacy of EGFR inhibitors. Polymorphic variants in
      members of the EGFR family could influence different biologic activities, such as
      ligands affinity, dimerization efficiency, kinase activity, expression levels,
      with a consequent impact in signalling pathways and cell behaviour. This study
      aimed to verify whether single nucleotide polymorphisms (SNPs) of EGFR family
      members could represent susceptibility factors able to influence the risk to
      develop CRC. Peripheral blood of 70 Italian colon cancer patients and 72 healthy
      controls was used as a source of genomic DNA to investigate EGFR, HER2 and HER3
      common non-synonymous SNPs. Genetic association tests were performed to verify a
      possible relationship with CRC. Evidence of genotype association was found for
      the R521K EGFR polymorphism under a dominant mode of inheritance (Mid-P=0.031).
      Genotypes with the variant allele of EGFR R521K SNP confer a risk reduction to
      develop CRC.

PMID- 21896993
TI  - Expression and prognostic relevance of Id1 in stage III esophageal squamous cell
      carcinoma.
AB  - Inhibitor of differentiation 1 (Id1) plays a role in cellular differentiation,
      proliferation, angiogenesis and tumor invasion. In current study, we investigated
      the expression of Id1 protein in 189 specimens of stage III ESCC by
      immunohistochemistry. The correlation between Id1 expression and
      clinicopathological parameters in terms of gender, age, tumor location,
      differentiation, pathological T stage and pathological N stage was also explored.
      Immunohistochemical staining showed that Id1 was expressed in all cases (100%).
      According to ROC curve, we selected 6.33 as the cutoff score. There were 95 cases
      in high expression group (> 6.33) and 94 cases in low expression group (? 6.33)
      respectively. The Id1 expression was associated negatively with differentiation,
      and positively with pathological N stage (P< 0.05, bothly); No significant
      correlation was observed between Id1 expression and gender, age, tumor location
      or pathological T stage (P> 0.05). As shown by the Kaplan-Meier curve, the
      overall survival rate of high expression group was significantly lower than that
      of low expression group (P< 0.001). The expression of Id1 protein has a close
      relationship with differentiation degree, pathological N stage and survival in
      ESCC patients. Id1 could be considered as a prognostic predictor for stage III
      ESCC patients.

PMID- 21896994
TI  - Nup88 mRNA overexpression in colorectal cancers and relationship with p53.
AB  - OBJECTIVES: We measured nucleoporin 88 (Nup88) mRNA expression in primary
      colorectal cancers to investigate its relationship with clinicopathological
      features and p53. METHODS: The primary cancer tissues, adjacent noncancerous
      tissues and the proximal and distant margins of normal mucosa were collected from
      73 colorectal cancer patients during surgery. Nup88 mRNA expression was measured
      on these fresh specimens and on colon cell lines HCT-116^{p53 + / + }</formula>
      and HCT-116^{p53 - / - }</formula> by RT-PCR while p53 mRNA and beta-actin as
      controls. Nup88 and p53 protein expression were then immunohistochemistrically
      examined in other 25 colorectal cancers specimens paraffin embedded and formalin
      fixed. RESULTS: Nup88 expression was higher in primary cancer tissues than in
      adjacent noncancerous tissues, and in the proximal and distant margins of normal
      mucosa. Overexpression of Nup88 mRNA was statistically associated with TNM stage
      (P=0.044), lymphatic metastasis (P=0.022), and cancer location (P=0.036), while
      not related to gender, age of patients and histological type, infiltration depth,
      and differentiation of cancers. The expression of Nup88 mRNA in the HCT-116^{p53 
      / - }</formula> cell line was not significantly different from expression in the
      HCT-116^{p53 + / +}cell line. And there was no correlation between Nup88 and p53
      protein expression (r=0.632, P=0.368). CONCLUSIONS: Nup88 mRNA was overexpressed
      in colorectal cancers and the overexpression was associated with cancer
      development and aggressiveness. Nup88 might be regard as essential contributor to
      nodal metastagenicity of colorectal cancer.

PMID- 21896995
TI  - Plasma chromogranin A: clinical implications in patients with castrate resistant
      prostate cancer receiving docetaxel chemotherapy.
AB  - OBJECTIVE: Development of castrate resistant prostate cancer (CRPC) indicates
      progressive disease with poor survival. Docetaxel has variable response with a
      good proportion of nonresponders. Neuroendocrine differentiation, hypothesised as
      one of the mechanisms behind development of CRPC, can be assessed by plasma
      Chromogranin A (CgA). We evaluated the clinical importance of circulating CgA in
      CRPC patients receiving Docetaxel. METHODS: Plasma CgA was assessed by ELISA in
      14 patients with CRPC receiving 3-weekly docetaxel. Baseline PSA, baseline CgA,
      PSA response, CgA response and clinical response to chemotherapy were evaluated
      and analysed. RESULTS: Increased plasma CgA was observed in 64.3% of patients.
      There was no correlation between baseline CgA and PSA. Two patients with PSA < 10
      ng/ml had elevated CgA. Baseline CgA was not influenced by variables such as site
      of metastasis and time to develop CRPC status. Seven patients (50%) had PSA
      response and 5 (36%) CgA-response. In 4 patients PSA response and CgA response
      were discordant. Compared to men with normal baseline CgA, a higher proportion of
      those with elevated baseline CgA had PSA response (55% vs 40%), symptomatic
      response (66% vs 40%) and radiological response (55% vs 20%). Two patients with
      symptomatic response had only CgA response. Three patients having disease
      progression despite PSA response had increasing CgA. CONCLUSIONS: CgA and PSA are
      complementary tumour markers in CRPC. CgA may help in predicting the response of
      docetaxel therapy. Rising CgA during therapy may be associated with bad prognosis
      whereas CgA response is likely to be associated with clinical response.

PMID- 21896996
TI  - LNA-based PCR clamping enrichment assay for the identification of KRAS mutations.
AB  - INTRODUCTION: KRAS mutations in colon carcinomas are associated with lack of
      response to anti-EGFR monoclonal antibody treatment. Therefore, patients must
      undergo genetic testing to be eligible for treatment. Several methods for KRAS
      mutation analysis exist, but many are not sensitive enough to detect a mutation
      in samples with low fraction of malignant cells. In the present study, we
      developed a KRAS mutations detection method that is both simple and sensitive.
      METHODS: Using a locked nucleic acid (LNA) containing oligonucleotide, we
      developed a PCR clamping method that preferentially amplifies the mutated over
      wild type KRAS. We evaluated the sensitivity of this method using serial
      dilutions of plasmids containing wild-type and mutated KRAS fragments.
      Additionally, KRAS mutation status was evaluated on 60 archived tissue samples of
      colon carcinoma, and compared to direct sequencing and high resolution melting
      (HRM) methods. RESULTS: The PCR clamping method could detect as little as 1%
      mutated DNA in the sample analyzed. Of the 29 KRAS mutations identified by the
      PCR clamping method, only 23 (79%) were identified by standard direct sequencing.
      The results of PCR clamping correlated with HRM results. CONCLUSIONS: LNA based
      PCR clamping method is a simple and highly sensitive method for the detection of
      KRAS mutations.

PMID- 21896997
TI  - Salivary and serum proteomics in head and neck carcinomas: before and after
      surgery and radiotherapy.
AB  - Several body fluids have been evaluated as new sources for cancer biomarker
      discovery. In this context, salivary and serum proteomics seem promising
      diagnostic and predictive tools for head and neck diseases. In the present study,
      we performed a proteomic analysis of saliva and serum from patients presenting
      head and neck squamous cell carcinoma (HNSCC) and compared the results before and
      after therapy. In saliva of cancer patients, we observed an altered protein
      profile, including over-expression of PLUNC and zinc-alpha-2-glycoprotein. Both
      proteins may contribute to control tumor growth and, therefore, represent targets
      for new analysis. We also detected serotransferrin and a modified transthyretin
      form with altered levels in serum from patients. Comparing preoperative and
      postreatment samples, the results showed that the protein profile after treatment
      reverted to a pattern closer to those observed for controls. These results add
      information on the role of secreted proteins in the cancer process and emphasize
      the potential of saliva and serum analysis for diagnosis and monitoring of HNSCC.

PMID- 21896998
TI  - Rectal mucosal quantitative galactose oxidase-Schiff reaction as an early
      detection biomarker for colorectal cancer: comparison to fecal occult stool blood
      test.
AB  - The galactose oxidase-Schiff (GOS) reaction detects D-galactose-beta-[1,3]-N
      acetyl-D-galactosamine. This is a T-antigen expressed in mucus from malignant
      cells and colonic mucosa adjacent to cancer but not in normal mucosa. Previous
      studies using a qualitative GOS assay proved to be of limited value for the
      detection of colorectal neoplasia. We used a newly developed quantitative GOS
      assay to determine its potential as an early detection biomarker for colorectal
      cancer. We completed a multi-center, prospective, cross-sectional cohort
      validation study consisting of 70 normal controls, 23 high-risk normal patients
      (polyp history or family history of colorectal cancer (CRC) with currently normal
      colonoscopy), 137 patients with adenomatous polyps, and 69 with colorectal
      cancers. Prior to colonoscopy, two samples of stool were collected via a rectal
      exam: one for FOBT, and one for GOS. The area under the ROC curve (AUC) for
      detecting colonic adenomas and cancer for normal colons, computed with logistic
      regression was 0.69 for GOS, 0.62 for FOBT, and 0.73 for GOS combined with FOBT.
      Adding GOS to FOBT did not significantly change the ROC of FOBT alone. GOS does
      not appear to be a suitable marker of colorectal neoplasia.

PMID- 21897000
TI  - MMP-9, homocysteine and CRP circulating levels are associated with intraluminal
      thrombus thickness of abdominal aortic aneurysms: new implication of the old
      biomarkers.
AB  - BACKGROUND: Abdominal aortic aneurysms (AAAs) are characterized by presence of
      high proteolytic activity, atherosclerotic lesions, extensive transmural
      inflammation and the presence of variably sized and shaped intraluminal thrombus
      (ILT). Therefore, we evaluated a possible association between plasma matrix
      metalloproteinase-9 (MMP-9), homocysteine (Hcy), high-sensitivity C-reactive
      protein (hsCRP) levels and ILT thickness in patients with AAA. METHODS: Plasma
      concentrations of MMP-9, Hcy and hsCRP were determined and ILT thickness was
      measured in 71 patients with AAA. They were divided into 2 groups according to
      ILT thickness: 34 patients with ILT mean thickness ? 9 mm and 37 patients with
      ILT < 9 mm. RESULTS: Plasma MMP-9 and CRP concentrations in patients with thin
      ILT were significantly higher than in group with thick ILT (medians 610 vs. 485
      ng/mL, p=0.00003, and 7.7 vs. 3.3 mg/L, p < 0.00001, respectively). In contrast,
      plasma Hcy concentrations in patients with thin ILT were significantly lower than
      in the group with thick ILT (medians 14.3 vs. 19.2 MUmol/L, p < 0.00001).
      Multiple regression models adjusted for age and AAA diameter showed that thin ILT
      is an independent predictor of high MMP-9 and CRP concentrations, while thick ILT
      predicts high Hcy concentrations. CONCLUSIONS: Association of higher plasma
      levels of MMP-9 and CRP with thin ILT may be related to two phenomena: thin
      thrombi convey more elastolysis-stimulating factors from blood to the AAA wall
      and thin thrombi convey more factors involved in proteolysis and inflammation
      from AAA wall to blood. The association of thin ILT with lower plasma Hcy
      concentrations may be related to the role of Hcy as a prothrombotic marker and
      needs further research.

PMID- 21896999
TI  - Platelet-stored angiogenesis factors: clinical monitoring is prone to artifacts.
AB  - BACKGROUND: The analysis of angiogenesis factors in the blood of tumor patients
      has given diverse results on their prognostic or predictive value. Since
      mediators of angiogenesis are stored in platelets, their measurement in plasma is
      sensitive to inadvertent platelet activation during blood processing. METHODS:
      Variants of blood withdrawal and plasma preparation were evaluated by ELISA for
      the detection of TSP-1, PF-4, VEGF and PD-ECGF. A total of 22 pancreatic cancer
      patients and 29 healthy volunteers were evaluated. RESULTS: Plasma preparation
      with the anticoagulant mix of citrate, theophylline, adenosine, dipyridamole
      (CTAD) and immediate blood processing at 4 degrees C was required for
      reproducible measurements of TSP-1, PF-4 and VEGF. Blood collection by venflon or
      inadvertent hemolysis during blood withdrawal caused significantly elevated TSP-1
      and PF-4 values. When optimized plasma preparation was applied, a significant
      increase of TSP-1 and VEGF in cancer patients was detected (P=0.006; P< 0.001).
      CONCLUSION: The reliable plasma analysis of circulating platelet-stored
      angiogenesis factors requires preparation with CTAD at 4 degrees C and blood
      collection by butterfly needle. Suboptimal procedures of plasma preparation are
      commonly applied in clinical monitoring of angiogenesis parameters which may
      account for the differences in reported plasma values and may have masked their
      predictive or prognostic marker potential.

PMID- 21897001
TI  - Circulating endothelial cells in patients with heart failure and left ventricular
      dysfunction.
AB  - INTRODUCTION AND AIMS: Acute and chronic heart failure may manifest different
      degrees of endothelial damage and angiogenesis. Circulating endothelial cells
      (CEC) have been identified as marker of vascular damage. The aim of our study was
      to evaluate the evolution of the CEC at different stages of patients with heart
      failure. We also investigated a potential correlation between CEC and markers of
      vascular damage and angiogenesis. METHODS: We studied 32 heart failure patients
      at hospital admission (acute phase) and at revision after 3 months (stable phase)
      and 32 controls. Circulating markers of endothelial damage (CEC; von Willebrand
      factor, vWF and soluble E-selectin, sEsel) and angiogenesis (vascular endothelial
      growth factor, VEGF and thrombospondin-1) were quantified. RESULTS: Levels of
      CEC, vWF, sEsel and VEGF are significantly higher in heart failure patients than
      in controls. Levels of CEC (36.9 +/- 15.3 vs. 21.5 +/- 10.0 cells/ml; p< 0.001),
      vWF (325 +/- 101 vs. 231 +/- 82%; p< 0.001) and VEGF (26.3 +/- 15.2 vs. 21.9 +/-
      11.9 ng/ml; p< 0.001) are significantly higher in the acute phase than in the
      stable phase of heart failure. CEC levels correlate with vWF and VEGF. RESULTS
      show than 100% of patients in acute phase and 37.5% in stable phase have levels
      of CEC higher than the 99th percentile of the distribution of controls (16
      cells/ml). Therefore, increases in CEC represent a relative risk of 9.5 for heart
      failure patients suffering from acute phase. CONCLUSIONS: CEC, in addition to
      being elevated in heart failure, correlate with vWF levels, providing further
      support for CEC as markers of endothelial damage. Levels of CEC are associated
      with the acute phase of heart failure and could be used as a marker of the
      worsening in heart failure.

PMID- 21897002
TI  - Endothelial nitric oxide synthase haplotypes are associated with preeclampsia in
      Maya mestizo women.
AB  - Preeclampsia is a specific disease of pregnancy and believed to have a genetic
      component. The aim of this study was to investigate if three polymorphisms in
      eNOS or their haplotypes are associated with preeclampsia in Maya mestizo women.
      A case-control study was performed where 127 preeclamptic patients and 263
      controls were included. Genotyped and haplotypes for the -768T->C, intron 4
      variants, Glu298Asp of eNOS were determined by PCR and real-time PCR allelic
      discrimination. Logistic regression analysis with adjustment for age and body
      mass index (BMI) was used to test for associations between genotype and
      preeclampsia under recessive, codominant and dominant models. Pairwise linkage
      disequilibrium between single nucleotide polymorphisms was calculated by direct
      correlation <formula>r^{2}</formula>, and haplotype analysis was conducted. Women
      homozygous for the Asp298 allele showed an association of preeclampsia. In
      addition, analysis of the haplotype frequencies revealed that the -786C-4b-Asp298
      haplotype was significantly more frequent in preeclamptic patients than in
      controls (0.143 vs. 0.041, respectively; OR =3.01; 95% CI = 1.74-5.23; P =2.9 *
      10<formula>^{-4}</formula>).Despite the Asp298 genotype in a recessive model
      associated with the presence of preeclampsia in Maya mestizo women, we believe
      that in this population the -786C-4b-Asp298 haplotype is a better genetic marker.

PMID- 21897003
TI  - Analysis of sputum markers in the evaluation of lung inflammation and functional
      impairment in symptomatic smokers and COPD patients.
AB  - The pivotal role of neutrophils and macrophages in smoking-related lung
      inflammation and COPD development is well-established. We aimed to assess whether
      sputum concentrations of Human Neutrophil Peptides (HNP), Neutrophil Elastase
      (NE), Interleukin-8 (IL-8), and Metalloproteinase-9 (MMP-9), major products of
      neutrophils and macrophages, could be used to trace airway inflammation and
      progression towards pulmonary functional impairment characteristic of COPD. Forty
      two symptomatic smokers and 42 COPD patients underwent pulmonary function tests;
      sputum samples were collected at enrolment, and 6 months after smoking cessation.
      HNP, NE, IL-8, MMP-9 levels were increased in individuals with COPD (p < 0.0001).
      HNP and NE concentrations were higher in patients with severe airways
      obstruction, as compared to patients with mild-to-moderate COPD (p =0.002). A
      negative correlation was observed between FEV<formula>_{1}</formula> and HNP, NE
      and IL-8 levels (p < 0.01), between FEV<formula>_{1}</formula>/FVC and HNP, NE
      and IL-8 levels (p< 0.01), and between NE enrolment levels and
      FEV<formula>_{1}</formula> decline after 2 years (p =0.04). ROC analysis, to
      discriminate symptomatic smokers and COPD patients, showed the following AUCs:
      for HNP 0.92; for NE 0.81; for IL-8 0.89; for MMP-9 0.81; for HNP, IL-8 and MMP-9
      considered together 0.981. The data suggest that the measurement of sputum
      markers may have an important role in clinical practice for monitoring COPD.

PMID- 21897004
TI  - Prognostic values of serum IP-10 and IL-17 in patients with pulmonary
      tuberculosis.
AB  - OBJECTIVE: To identify patients at high risk of relapse after anti-tuberculosis
      (TB) therapy or with poor long-term outcomes. METHODS: Fifty-one patients with
      pulmonary TB: 7 were classified as high association with both cavitations on
      initial chest radiography and positive sputum smear/cultures after two months of
      anti-TB treatment (HA group); 19 medium association (MA, one risk alone); and 25
      low association (LA, neither risk). Serum interferon (IFN)-gamma-inducible
      protein 10 (IP-10), interleukin-17 (IL-17), and C-reactive protein levels were
      investigated. RESULTS: There was a trend towards higher serum IP-10 levels
      (p=0.042) for HA patients throughout the 6-month treatment period. Month-2 IP-10
      levels were higher in the HA than in the MA/LA group (656.2 +/- 234.4 vs. 307.6
      +/- 258.5 pg/ml, adjusted p =0.005). Receiver operating characteristic curves
      showed that the risk of relapse was well-captured by month-2 IP-10 levels at a
      cut-off value of 431 pg/ml (AUC=0.857, 95% CI 0.75-0.97, p =0.003). Month-2 serum
      IL-17 levels were lower in non-survivors than survivors (15.7 +/- 2.9 pg/ml vs.
      24.6 +/- 8.2 pg/ml, p=0.001). Multivariate analysis demonstrated that a month-2
      serum IL-17 level of ? 17 pg/ml (p =0.026) was independently associated with all
      cause mortality. CONCLUSIONS: Serum IP-10 and IL-17 levels after 2 months of anti
      TB treatment may be biomarkers for estimating risk of both cavitation and delayed
      sputum conversion, and for predicting long-term mortality, respectively.

PMID- 21897005
TI  - On chip immuno-affinity profiling of cancer- and benign hyperplasia-associated
      free prostate specific antigen.
AB  - Prostate specific antigen (PSA) exhibits pronounced heterogeneity in both primary
      structure and glycan composition, resulting in the existence of different
      molecular forms. Investigation of PSA structure is a demanding task facing
      limitations due to inadequate sensitivity of analytical techniques and low
      concentrations of the different forms. This study aimed to profile free PSA
      (fPSA), especially lower molecular mass species lacking detailed classification,
      in normal seminal plasma and in sera from subjects with benign hyperplasia (BPH)
      or cancer of the prostate (PCa) as samples of known clinical relevance. fPSA
      forms were separated from complex proteomes on chips with immobilized anti-fPSA
      antibody followed by detection using surface-enhanced laser desorption/ionization
      time of flight mass spectrometry. At least 39 fPSA-immunoreactive species,
      ranging from 3-29 kDa were detected in seminal plasma. General fPSA profiles in
      seminal plasma and sera were similar, but differed in the abundance and presence
      of particular peaks/clusters of the lower molecular mass species. No striking
      difference in fPSA forms was observed between BPH and PCa samples, but some
      distinct peaks varied in intensity and frequency within or between groups.
      Obtained data verify fPSA heterogeneity that might be important for better
      exploration of all their molecular and marker potentials.

PMID- 21897006
TI  - Amyloid-beta42 activates the expression of BACE1 through the JNK pathway.
AB  - The sequential endoproteolytic cleavages operated by the gamma-secretase and the
      beta-secretase (BACE1) on the amyloid-beta protein precursor (AbetaPP) result in
      the production of the amyloid-beta (Abeta) species, with two C-terminal variants,
      at residue 40 or at residue 42. Accumulation in brain tissue of small, soluble
      aggregates of Abeta42 is the major pathogenic event of Alzheimer's disease (AD).
      However, the physiologic activity of Abeta peptides is still elusive. Here, we
      show that expression of BACE1 is regulated by Abeta42, which augments BACE1 gene
      transcription through the JNK/c-jun signaling pathway. Of note, Abeta40 has much
      less effect on BACE1 expression. These findings unveil a positive feedback loop
      in which gamma-secretase cleavage of AbetaPP releases a functionally-active
      peptide, Abeta42, that promotes BACE1 transcription. Thus, gene expression
      induced by Abeta42 may have implications in the neuronal dysfunction and
      degeneration that occurs in AD.

PMID- 21897007
TI  - CSF Abeta1-42 levels and glucose metabolism in Alzheimer's disease.
AB  - Glucose dysmetabolism has been consistently associated with an increased risk of
      cognitive disorders, and brain insulin resistance could play a role in
      Alzheimer's disease (AD) pathogenesis. Recent evidence suggests that
      cerebrospinal fluid (CSF) biomarkers may reflect the brain pathology in AD. We
      have investigated the relationship between CSF concentrations of amyloid-beta
      peptide 1-42 (Abeta1-42), total tau, and phosphorylated tau (ptau-181) and plasma
      and CSF glucose levels in a cohort of 94 newly diagnosed non-diabetics AD
      patients. We report that CSF Abeta1-42 level was inversely associated with CSF to
      plasma glucose ratio (Spearman's coefficient = -0.27, p = 0.008). This
      relationship remained after adjustment for age, gender, body mass index,
      hypertension, and MMSE score (beta [SE] of linear regression = -0.93 [0.37], p =
      0.01). In stratified analysis, this relationship was observed only in patients
      who did not carry the apolipoprotein E4 allele. No significant relationship was
      found between glucose levels and total tau or phosphorylated tau 181. These
      results support the idea that a link between glucose dysmetabolism and the
      amyloid pathway may exist in the pathogenesis of AD.

PMID- 21897008
TI  - Bacterial surface display of a co-factor containing enzyme, omega-transaminase
      from Vibrio fluvialis using the Bacillus subtilis spore display system.
AB  - To improve the conventional bacterial surface display systems and to display a co
      factor containing enzyme, omega-transaminase from Vibrio fluvialis, which needs
      pyridoxal phosphate (PLP) for efficient transamination, Bacillus subtilis spore
      display system with cotG, as an anchoring motif was used. Flow cytometry of the
      B. subtilis spore-expressing omega-transaminase proved its surface localization
      on the spore. The enzymatic activity of the spore expressing omega-transaminase
      was more than 30 times higher than that of the host spore. Protease treatment of
      the omega-transaminase displaying spores resulted in decreased transaminase
      activity, which is in keeping with the surface location of the fusion protein,
      CotG-omega-transaminase.

PMID- 21897009
TI  - Actin stress fiber retraction and aggresome formation is a common cellular
      response to actin toxins.
AB  - F-actin-stabilizing drugs induce actin aggresome formation. In this study, we
      found that an actin-depolymerizing drug, latrunculin A (LatA), induced actin
      aggresomes. Actin stress fibers were retracted and disappeared in minutes, but a
      large aggresome formed in consequence of LatA treatment. Because cytochalasin D
      and mycalolide also induced aggresome formation, these results suggest that actin
      aggresome formation is a common cellular response to actin toxins.

PMID- 21897010
TI  - Two Sec13p homologs, AtSec13A and AtSec13B, redundantly contribute to the
      formation of COPII transport vesicles in Arabidopsis thaliana.
AB  - COPII vesicles mediate protein transport from ER to Golgi. Sec13 makes up lattice
      structure with Sec31 to form COPII vesicles. We analyzed expression of two
      Arabidopsis thaliana Sec13 homologs, AtSec13A and AtSec13B. AtSec13A was
      expressed in most parts of seedlings, while AtSec13B was partially expressed.
      Interaction of AtSec13A or AtSec13B with Sec31 homolog was demonstrated by
      bimolecular fluorescence complementation (BiFC).

PMID- 21897011
TI  - Decolorization of synthetic dyes and biodegradation of bisphenol a by laccase
      from the edible mushroom, Grifola frondosa.
AB  - A major laccase isozyme from Grifola frondosa (Lac 1) was found to be effective
      for decolorizing of synthetic dyes and degrading of bisphenol A. The oxidative
      capability of Lac 1 toward synthetic dyes and bisphenol A was enhanced in the
      presence of the redox mediator, 1-hydroxybenzotriazole. The major product from
      the degradation of bisphenol A by Lac 1 was determined to be 4-isopropenylphenol.

PMID- 21897012
TI  - Effects of daintain/AIF-1 on beta cell dysfunction in INS-1 cells.
AB  - We investigated the effects of daintain/AIF-1, a novel inflammatory cytokine, on
      INS-1beta cells. Cells incubated with daintain/AIF-1 showed decreased cell
      viability and glucose-stimulated insulin secretion, as well as upregulated
      apoptosis and NO production. These deleterious effects of daintain/AIF-1 indicate
      that daintain/AIF-1 plays important roles in the dysfunction of pancreatic beta
      cells in type-1 diabetes.

PMID- 21897013
TI  - Plasma carotenoid concentrations before and after supplementation with
      astaxanthin in middle-aged and senior subjects.
AB  - A randomized, double-blind human trial was conducted to assess the effect on the
      plasma carotenoid concentration of 4- or 12-week astaxanthin supplementation (1
      or 3 mg/d) of 20 Japanese middle-aged and senior subjects. The plasma carotenoid
      concentration was significantly higher after the astaxanthin supplementation than
      that before in both the 1 mg/d (10 subjects) and 3 mg/d (10 subjects) groups.

PMID- 21897014
TI  - Thermal stability of cytochrome c5 of pressure-sensitive Shewanella
      livingstonensis.
AB  - Cytochrome c5 of pressure-sensitive Shewanella livingstonensis (SL cytc5)
      exhibits lower thermal stability than a highly homologous counterpart of pressure
      tolerant Shewanella violacea. This stability difference is due to an enthalpic
      effect that can be attributed to the amino acid residue at position 50 (Leu or
      Lys). These cytc5 proteins are appropriate materials for understanding the
      protein stability mechanism.

PMID- 21897015
TI  - Alteration of ethanol tolerance caused by the deficiency in the genes associated
      with histone deacetylase complex in budding yeast.
AB  - Upon exposure to 8% ethanol, survival and growth of yeast strains deficient in
      histone deacetylase complex genes was examined. Of the 18 mutants tested, the
      Deltasir3 and Deltasir4 strains showed higher resistance to ethanol, while the
      Deltarco1, Deltahos3, Deltahda2, and Deltahst1 strains were more sensitive than
      the wild type. Furthermore, these ethanol-resistant patterns varied under aerobic
      and anaerobic culture conditions.

PMID- 21897016
TI  - Cloning and expression of the endo-1,3(4)-beta-glucanase gene from Paecilomyces
      sp. FLH30 and characterization of the recombinant enzyme.
AB  - The cDNA encoding beta-1,3(4)-glucanase, named PsBg16A, from Paecilomyces sp.
      FLH30 was cloned, sequenced, and over expressed in Pichia pastoris, with a yield
      of about 61,754 U mL-1 in a 5-L fermentor. PsBg16A has an open reading frame of
      951 bp encoding 316 amino acids, and the deduced amino acid sequence of PsBg16A
      revealed that it belongs to glycoside hydrolase family 16. The purified
      recombinant PsBg16A had a pH optimum at 7.0 and a temperature optimum at 70 
      degrees C, and randomly hydrolyzed barley beta-glucan, lichenin, and laminarin,
      suggesting that it is a typical endo-1,3(4)-beta-glucanase (EC 3.2.1.6) with
      broad substrate specificity for beta-glucans.

PMID- 21897017
TI  - Characterization of glucosylceramides in leaves of the grass family (Poaceae):
      Pooideae has unsaturated hydroxy fatty acids.
AB  - The glucosylceramide components were characterized in the 33 species of the grass
      family (Poaceae). Pooideae contained 4-hydroxy-8-sphingenines [i.e., t18:1(8Z)
      plus t18:1(8E)] as major components, the relative levels of t18:1(8Z) being
      higher than those of the 8-E isomers. 2-Hydroxy arachidic acid was a major
      component in all species other than Pooideae, whereas Pooideae had a high content
      of 2-hydroxytetracosenoic acid.

PMID- 21897018
TI  - Microbial communities associated with acetate-rich gas-petroleum reservoir
      surface facilities.
AB  - We evaluated the microbial communities in acetate-rich production waters from
      separators of a high-temperature gas-petroleum reservoir in Higashi-Niigata,
      Japan. Bacterial and archaeal 16S rRNA gene libraries constructed from these
      waters were dominated by Acetobacterium-, Methanofollis-, and Methanosarcina
      related sequences. The libraries constructed from enrichment cultures of the
      production waters were dominated by sequences related to the Acetobacterium- and
      Methanofollis-related sequences.

PMID- 21897019
TI  - Chemical identification and ethological function of soldier-specific secretion in
      Japanese subterranean termite Reticulitermes speratus (Rhinotermitidae).
AB  - We identified the soldier-specific compounds in the Japanese subterranean
      termite, Reticulitermes speratus, to clarify their ethological roles. Silica gel
      column chromatography separated one major soldier-specific compound in the hexane
      fraction accounting for 70-80% of the total amount of the fraction, while
      cuticular hydrocarbons constituted the rest. We identified the compound as beta
      selinene by gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic
      resonance (NMR) spectroscopy. Comparative GC analyses of the major exocrine
      glands detected the compound in the soldier's frontal gland. Both soldiers and
      workers made aggregation to the hexane fraction, as well as to the crushed heads
      and head extract of the soldiers. They did not aggregate to cuticular
      hydrocarbons, making it likely that beta-selinene was the aggregation pheromone
      in this species. The opportunistic predator of this termite, Lasius japonicus,
      was also attracted to the compounds. The ant workers, therefore, would use the
      termite aggregation pheromone as a kairomone for hunting them.

PMID- 21897021
TI  - Aspergillus oryzae laeA regulates kojic acid synthesis genes.
AB  - Kojic acid synthesis genes regulation was investigated in Aspergillus oryzae. Our
      results indicate that kojic acid production was lost in the laeA disruption
      strain, but was recovered in the LaeA complement strain. Real-time PCR also
      confirmed that expression of kojic acid biosynthesis genes decreased in the laeA
      disruption strain, indicating that these genes are under the control of LaeA.

PMID- 21897020
TI  - Total biosynthesis of diterpene aphidicolin, a specific inhibitor of DNA
      polymerase alpha: heterologous expression of four biosynthetic genes in
      Aspergillus oryzae.
AB  - Clustering of biosynthetic genes for producing fungal secondary metabolites,
      which frequently consist of less than ten genes, has been recognized with
      numerous genomes. The heterologous expression of whole genes in the clusters will
      therefore produce various types of natural products when using a suitable fungal
      host. We introduced the whole gene cluster for the biosynthesis of diterpene
      aphidicolin into the fungal quadruple auxotrophic host, Aspergillus oryzae, by
      using four different vectors (pTAex3, pPTRI, pUSA and pAdeA) which harbor a
      starch-inducible promoter/terminator to examine the expression conditions. The
      resulting quadruple transformant carrying the genes of geranylgeranyl diphosphate
      synthase PbGGS, terpene synthase PbACS, and two monooxygenases (PbP450-1 and
      PbP450-2) produced aphidicolin. The double and triple transformants also
      respectively produced aphidicolan-16beta-ol and 3-deoxyaphidicolin. Alternative
      host Saccharomyces cerevisiae carrying the genes, PbGGS and PbACS, produced key
      intermediate aphidicolan-16beta-ol. This is the first example of a total
      biosynthesis of terpenoids using fungal hosts.

PMID- 21897022
TI  - A novel compound, L34, induced apoptosis in human gastric cancer cells.
AB  - Selectively apoptosis-targeting compounds in gastrointestinal cancers attract
      broad interest. Here, we investigated a synthetic sulfonamide, 4-bromo-N-(5-ethyl
      5H-pyrido[4,3-b]indol-8-yl)benzenesulfonamide (L34). It showed high activity
      against gastric cancer cells SGC-7901, causing apoptosis, which was associated
      with downregulation of caspase-3 and XIAP, upegulation of cleaved caspase-3, and
      cleavage of PARP. Hence, L34 might be a potent chemotherapeutic agent against
      human gastric cancer.

PMID- 21897023
TI  - Cloning of a FLOWERING LOCUS T ortholog in Wasabia japonica (Matsum).
AB  - A FLOWERING LOCUS T ortholog (WjFT) was identified in Wasabia japonica.
      Heterologous expression of WjFT remarkably promoted the flowering of Arabidopsis.
      The expression of WjFT was examined in field-grown wasabi in October and November
      of 2009, and February of 2010 because the differentiation of flower buds occurs
      in autumn in field-grown wasabi. No expression of WjFT was detected in October,
      it was slightly increased in November, and highly increased in February. WjFT
      might be useful for examining the flowering response of wasabi.

PMID- 21897024
TI  - Purification and characterization of a magnesium ion requiring N-acetyl-D
      glucosamine specific lectin from seeds of Quercus ilex L.
AB  - A new magnesium ion requiring N-acetyl-D-glucosamine specific lectin QIL was
      purified to electrophoretic homogeneity from seeds of Quercus ilex L. through
      successive steps of (i) lectin extraction, (ii) ammonium sulphate (30-50%)
      fractionation, (iii) diethylaminoethyl (DEAE)-cellulose chromatography, (iv)
      carboxymethyl (CM)-cellulose chromatography, and (v) Sephadex G-75
      chromatography. The lectin, having specific activity of 25,600 hemagglutination
      units (HAU)/mg of protein, was found to be a monomeric protein with a native
      molecular weight of 13.2 kDa. N-Acetyl-D-glucosamine was found to exhibit most
      potent inhibitory action on the lectin activity among all the sugars tested. The
      lectin was also found to exhibit specificity for human blood groups A, B, and AB.
      It was converted to the corresponding apo-lectin by ethylenediaminetetraacetic
      acid (EDTA) treatment followed by buffer dialysis. The apo-lectin exhibited a
      specific and characteristic requirement for magnesium ions for the expression of
      its activity.

PMID- 21897025
TI  - An efficient and novel screening model for assessing the bioactivity of extracts
      against multidrug-resistant Pseudomonas aeruginosa using Caenorhabditis elegans.
AB  - As a large number of multidrug-resistant bacteria have emerged, and there is an
      urgent need for the development of new antibacterial agents. In this study, we
      developed a liquid-based slow killing assay to be carried out in standard 96-well
      microtiter plates. This screening method was designed to facilitate high
      throughput screening of small molecules and extracts. In antibiotic rescue
      assays, the Caenorhabditis elegans multidrug-resistant Pseudomonas aeruginosa
      infection model displayed a high degree of drug resistance in vivo and in vitro.
      We used the method to screen 1,300 extracts, and found 36 extracts (2.7%) which
      prolonged the survival of infected nematodes, and four (0.3%) of these extracts
      showed in vitro and in vivo anti-multidrug resistant P. aeruginosa activity.
      These results indicate that the whole-animal C. elegans multidrug-resistant
      bacterial model can be used to screen antibacterial compounds, and can also be
      useful for bioactive compounds which most likely cannot be identified in vitro.

PMID- 21897026
TI  - Characterization of two isozymes of coniferyl alcohol dehydrogenase from
      Streptomyces sp. NL15-2K.
AB  - We purified two isozymes of coniferyl alcohol dehydrogenase (CADH I and II) to
      homogeneity from cell-free extracts of Streptomyces sp. NL15-2K. The apparent
      molecular masses of CADH I and II were determined to be 143 kDa and 151 kDa
      respectively by gel filtration, whereas their subunit molecular masses were
      determined to be 35,782.2 Da and 37,597.7 Da respectively by matrix-assisted
      laser-desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS).
      Thus, it is probable that both isozymes are tetramers. The optimum pH and
      temperature for coniferyl alcohol dehydrogenase activity were pH 9.5 and 45 
      degrees C for CADH I and pH 8.5 and 40  degrees C for CADH II. CADH I oxidized
      various aromatic alcohols and allyl alcohol, and was most efficient on cinnamyl
      alcohol, whereas CADH II exhibited high substrate specificity for coniferyl
      alcohol, and showed no activity as to the other alcohols, except for cinnamyl
      alcohol and 3-(4-hydroxy-3-methoxyphenyl)-1-propanol. In the presence of NADH,
      CADH I and II reduced cinnamaldehyde and coniferyl aldehyde respectively to the
      corresponding alcohols.

PMID- 21897027
TI  - Purification and characterization of a novel (R)-imine reductase from
      Streptomyces sp. GF3587.
AB  - The (R)-imine reductase (RIR) of Streptomyces sp. GF3587 was purified and
      characterized. It was found to be a NADPH-dependent enzyme, and was found to be a
      homodimer consisting of 32 kDa subunits. Enzymatic reduction of 10 mM 2-methyl-1
      pyrroline (2-MPN) resulted in the formation of 9.8 mM (R)-2-methylpyrrolidine
      ((R)-2-MP) with 99% e.e. The enzyme showed not only reduction activity for 2-MPN
      at neutral pH (6.5-8.0), but also oxidation activity for (R)-2-MP under alkaline
      pH (10-11.5) conditions. It appeared to be a sulfhydryl enzyme based on the
      sensitivity to sulfhydryl specific inhibitors. It was very specific to 2-MPN as
      substrate.

PMID- 21897028
TI  - Formation of 4-keto-D-aldopentoses and 4-pentulosonates (4-keto-D-pentonates)
      with unidentified membrane-bound enzymes from acetic acid bacteria.
AB  - In our previous study, a new microbial reaction yielding 4-keto-D-arabonate from
      2,5-diketo-D-gluconate was identified with Gluconacetobacter liquefaciens RCTMR
      10. It appeared that decarboxylation and dehydrogenation took place together in
      the reaction. To analyze the nature of the reaction, investigations were done
      with the membrane fraction of the organism, and 4-keto-D-arabinose was confirmed
      as the direct precursor of 4-keto-D-arabonate. Two novel membrane-bound enzymes,
      2,5-diketo-D-gluconate decarboxylase and 4-keto-D-aldopentose 1-dehydrogenase,
      were involved in the reaction. Alternatively, D-arabonate was oxidized to 4-keto
      D-arabonate by another membrane-bound enzyme, D-arabonate 4-dehydrogenase. More
      directly, D-arabinose oxidation was examined with growing cells and with the
      membrane fraction of G. suboxydans IFO 12528. 4-Keto-D-arabinose, the same
      intermediate as that from 2,5-diketo-D-gluconate, was detected, and it was
      oxidized to 4-keto-D-arabonate. Likewise, D-ribose was oxidized to 4-keto-D
      ribose and then it was oxidized to 4-keto-D-ribonate. In addition to 4-keto-D
      aldopentose 1-dehydrogenase, the presence of a novel membrane-bound enzyme, D
      aldopentose 4-dehydrogenase, was confirmed in the membrane fraction. The
      formation of 4-keto-D-aldopentoses and 4-keto-D-pentonates (4-pentulosonates) was
      finally confirmed as reaction products of four different novel membrane-bound
      enzymes.

PMID- 21897029
TI  - Evaluation of the use of the tobacco PR-1a promoter to monitor defense gene
      expression by the luciferase bioluminescence reporter system.
AB  - Because of their marked responsiveness to induction signals, genes encoding
      pathogenesis-related proteins are used as markers to monitor defense gene
      expression in plants. To develop a non-invasive bioluminescence reporter assay
      system, we tested acidic PR-1 gene promoters from tobacco and Arabidopsis. These
      two promoters share common regulatory elements and are believed to show similar
      responsiveness to various stimuli but the results of transient expression assays
      by microprojectile bombardment of various plant cells and npr1 mutant Arabidopsis
      suggest that the tobacco PR-1a promoter is superior to its Arabidopsis
      counterpart in terms of responsiveness to salicylic acid treatment. Transgenic
      Arabidopsis seedlings harboring the tobacco PR-1a promoter fused to firefly
      luciferase showed marked induction in response to treatment with chemicals that
      induce defense gene expression in plants. These results suggest that the tobacco
      PR-1a promoter is applicable in monitoring defense-gene expression in various
      plant species.

PMID- 21897030
TI  - Chitinase from Autographa californica multiple nucleopolyhedrovirus: rapid
      purification from Sf-9 medium and mode of action.
AB  - Autographa californica multiple nucleopolyhedrovirus (AcMNPV) chitinase is
      involved in the final liquefaction of infected host larvae. We purified the
      chitinase rapidly to homogeneity from Sf-9 cells infected with AcMNPV by a simple
      procedure using a pepstatin-aminohexyl-Sepharose column. In past studies, a
      recombinant AcMNPV chitinase was found to exhibit both exo- and endo-chitinase
      activities by analysis using artificial substrates with a fluorescent probe. In
      this study, however, we obtained more accurate information on the mode of action
      of the chitinase by HPLC analysis of the enzymatic products using natural
      oligosaccharide and polysaccharide substrates. The AcMNPV chitinase hydrolyzed
      the second beta-1,4 glycosidic linkage from the non-reducing end of the chitin
      oligosaccharide substrates [(GlcNAc)(n), n=4, 5, and 6], producing the beta
      anomer of (GlcNAc)2. The mode of action was similar to that of Serratia
      marcescens chitinase A (SmChiA), the amino acid sequence of which is 60.5%
      homologous to that of the AcMNPV enzyme. The enzyme also hydrolyzed solid beta
      chitin, producing only (GlcNAc)2. The AcMNPV chitinase processively hydrolyzes
      solid beta-chitin in a manner similar to SmChiA. The processive mechanism of the
      enzyme appears to be advantageous in liquefaction of infected host larvae.

PMID- 21897031
TI  - Isolation and characterization of N-acylhomoserine lactonase from the
      thermophilic bacterium, Geobacillus caldoxylosilyticus YS-8.
AB  - Geobacillus caldoxylosilyticus YS-8, which was isolated from volcanic soil in
      Indonesia, was found to degrade various N-acylhomoserine lactones (AHLs) with
      different lengths and acyl side-chain substitutions over a wide temperature range
      of 30-70  degrees C. The purified AHL-degrading enzyme showed a single band of 32
      kDa, and its N-terminal amino acid sequence was determined to be ANVIKARPKLYVMDN,
      tentatively suggesting that the AHL-degrading enzyme was AHL lactonase. The AHL
      degrading activity of the purified enzyme was maximized at pH 7.5 and 50  degrees
      C, and it retained about 50% of its activity even after a heat treatment at 60 
      degrees C for 3 h, exhibiting properties consistent with a thermostable enzyme.
      The mass spectrometric analysis demonstrated that the AHL-degrading enzyme
      catalyzed lactone ring opening of N-3-oxohexanoyl-L-homoserine lactone and N
      hexanoyl-L-homoserine lactone by hydrolyzing the lactones and working as an AHL
      lactonase.

PMID- 21897032
TI  - Comparison of acyl-CoA synthetic activities and enantioselectivity toward 2
      arylpropanoic acids in firefly luciferases.
AB  - Measurement of thioesterification activities for dodecanoic acid (C12) and
      ketoprofen was done using five firefly luciferases, from Pyrocoelia miyako (PmL),
      Photinus pyralis (PpL), Luciola cruciata (LcL), Hotaria parvura (HpL), and
      Luciola mingrelica (LmL). Among these, PmL, PpL, and LcL showed the expected
      thioesterification activities toward both substrates. All the enzymes exhibited
      (R)-enantioselectivity toward ketoprofen, which had same tendency as firefly
      luciferase from Luciola lateralis (LUC-H). HpL and LmL, however, did not accept
      ketoprofen, although they had thioesterification activity toward C12. These
      results indicate that the substrate acceptance of luciferases for the
      thioesterification reaction varies dramatically relying on the origin of firefly.
      Hence we focused primarily on PmL and investigated the effect of pH on enzymatic
      activity. In addition, by determining the kinetic parameters at various pH
      values, we verified that the k(cat) parameter contributed to the preferential
      enantioselectivity of this enzyme.

PMID- 21897033
TI  - Expression analysis of the VTC2 and VTC5 genes encoding GDP-L-galactose
      phosphorylase, an enzyme involved in ascorbate biosynthesis, in Arabidopsis
      thaliana.
AB  - Arabidopsis thaliana contains two GDP-L-galactose phosphorylase genes, VTC2 and
      VTC5, which are critical for ascorbate (AsA) biosynthesis. We investigated the
      expression levels of both VTC2 and VTC5 genes in wild-type A. thaliana and the
      AsA deficient mutants during early seedling growth. Ascorbate accumulated to an
      equal extent in all genotypes up to 5 d post-germination (DPG). The transcript
      level of VTC2 was dominant, and increased in parallel with AsA accumulation in
      the wild type. On the other hand, the expression of VTC5 compensated for the
      reduced VTC2 transcription levels in the AsA deficient mutant vtc2-1 in young
      seedlings. A luciferase activity assay indicated that the VTC5 promoter was more
      active in young (2 DPG) cotyledons and that the VTC2 and VTC5 promoters drove a
      day-to-night variation in expression. The present work provides clues to the
      precise roles of VTC2 and VTC5 in AsA biosynthesis in A. thaliana at the young
      seedling stage.

PMID- 21897034
TI  - Potential of carotenoids in aquatic yeasts as a phylogenetically reliable marker
      and natural colorant for aquaculture.
AB  - Apart from Xanthophyllomyces dendrorhous, pink colony-forming yeasts have not
      been examined as a pigmentation source in captive animals. In this study, aquatic
      yeasts were screened with a view to abundances of carotenoids. Phylogenetic
      analyses of these caroetnoid-rich yeasts based on large subunit ribosomal RNA
      gene (LSU rDNA) partial sequences showed that all belonged to the order
      Sporidiobolales. Both the qualitative and the quantitative differences in
      carotenoids between the yeasts appeared to be consistent with their phylogenetic
      affiliations. This information might be useful in the selection of pigment-rich
      yeasts containing specific carotenoids from a large number of strains. We also
      found, for the first time, the potential of a pigment-rich Rhodotorula strain as
      a colorant for aquaculture. The integuments of tilapia and carp fed the alkali
      treated cells of strain Rhodotorula dairenensis Sag 17 were pigmented after 3
      months of cultivation. The fish integuments retained the yeast carotenes shortly
      after the start of feeding, and were converted to the fish-specific xanthophylls
      in vivo.

PMID- 21897035
TI  - Quantification of pork, chicken and beef by using a novel reference molecule.
AB  - A standard plasmid was constructed as a novel reference molecule for use in real
      time quantitative PCR assays to verify the identity of beef, pork, chicken,
      mutton, and horseflesh. The plasmid contained a target domain of the cytochrome b
      (cyt b) gene and an artificial DNA sequence. Primers CO-F and CO-R, and probe CO
      P were specifically designed to detect the artificial sequence. The calculated R2
      values of the standard curves (103-107 copies per reaction) for the five species
      ranged between 0.998 and 0.999 in the quantification analysis. The constructed
      plasmid provides a universal method for measuring the copy number of cyt b DNA in
      minced meat. This method would be a useful procedure for verifying food labels.

PMID- 21897037
TI  - Effect of pamamycin-607 on secondary metabolite production by Streptomyces spp.
AB  - The effect of the aerial mycelium-inducing compound, pamamycin-607, on antibiotic
      production by several Streptomyces spp. was examined. Exposure to 6.6 uM
      pamamycin-607 stimulated by 2.7 fold the puromycin production by Streptomyces
      alboniger NBRC 12738, in which pamamycin-607 had first been isolated, and
      restored aerial mycelium formation. Pamamycin-607 also stimulated the respective
      production of streptomycin by S. griseus NBRC 12875 and that of cinerubins A and
      B by S. tauricus JCM 4837 by approximately 1.5, 1.7 and 1.9 fold. The antibiotic
      produced by Streptomyces sp. 91-a was identified as virginiamycin M(1), and its
      synthesis was enhanced 2.6 fold by pamamycin-607. These results demonstrate that
      pamamycin-607 not only restored or stimulated aerial mycelium formation, but also
      stimulated secondary metabolite production.

PMID- 21897036
TI  - Production of starch with antioxidative activity by baking starch with organic
      acids.
AB  - A starch ingredient with antioxidative activity, as measured by the DPPH method,
      was produced by baking corn starch with an organic acid; it has been named ANOX
      sugar (antioxidative sugar). The baking temperature and time were fixed at 170 
      degrees C and 60 min, and the organic acid used was selected from preliminary
      trials of various kinds of acid. The phytic acid ANOX sugar preparation showed
      the highest antioxidative activity, but the color of the preparation was almost
      black; we therefore selected L-tartaric acid which had the second highest
      antioxidative activity. The antioxidative activity of the L-tartaric acid ANOX
      sugar preparation was stable against temperature, light, and enzyme treatments
      (alpha-amylase and glucoamylase). However, the activity was not stable against
      variations in water content and pH value. The antioxidative activity of ANOX
      sugar was stabilized by treating with boiled water or nitrogen gas, or by pH
      adjustment.

PMID- 21897038
TI  - Effects of peanut-skin procyanidin A1 on degranulation of RBL-2H3 cells.
AB  - Peanut skin contains large amounts of polyphenols having antiallergic effects. We
      found that a peanut-skin extract (PSE) inhibits the degranulation induced by
      antigen stimulation of rat basophilic leukemia (RBL-2H3) cells. A low-molecular
      weight fraction from PSE, PSEL, also had inhibitory activity against allergic
      degranulation. A main polyphenol in PSEL was purified by gel chromatography and
      fractionated by YMC-gel ODS-AQ 120S50 column. Electrospray ionization mass
      spectrometry (ESI-MS) analysis of the purified polyphenol gave m/z 599 [M+Na]+.
      Based on the results of 1H-NMR, 13C-NMR spectra, and optical rotation analysis,
      the polyphenol was identified as procyanidin A1. It inhibited the degranulation
      caused by antigen stimulation at the IC50 of 20.3 uM. Phorbol-12-myristate-13
      acetate (PMA) and 2,5,-di(tert-butyl)-1,4-hydroquinone (DTBHQ)-induced processes
      of degranulation were also inhibited by procyanidin A1. These results indicate
      that peanut-skin procyanidin A1 inhibits degranulation downstream of protein
      kinase C activation or Ca2+ influx from an internal store in RBL-2H3 cells.

PMID- 21897039
TI  - Functional compounds in fermented buckwheat sprouts.
AB  - Fermented buckwheat sprouts (FBS) are used as multifunctional foods. Their
      production process includes fermentation with lactic acid bacteria. The major
      strains were found to include Lactobacillus plantarum, Lactobacillus brevis,
      Lactobacillus pentosus, Lactococcus lactis subsp. lactis, and Pediococcus
      pentosaceus in an investigation of the lactic acid bacteria. We searched for the
      functional components, and nicotianamine (NA) and 2"-hydroxynicotianamine (HNA)
      were identified as angiotensin I-converting enzyme (ACE) inhibitors. NA and HNA
      increased during fermentation. Indole-3-ethanol was identified as an antioxidant
      (a SOD active substance), and may have been generated from tryptophan during
      fermentation because it was not contained in green buckwheat juice. A safety test
      demonstrated that FBS contained were safe functional food components, showing
      negative results in buckwheat allergy tests. Any buckwheat allergy substances
      might have been degraded during the fermentation process.

PMID- 21897040
TI  - The impact of aridification and vegetation type on changes in the community
      structure of methane-cycling microorganisms in Japanese wetland soils.
AB  - Over the years, the wetlands covered by Sphagnum in Bibai, Japan have been
      turning into areas of aridity, resulting in an invasion of Sasa into the bogs.
      Yet little is known about the methane-cycling microorganisms in such
      environments. In this study, the methanotrophic, methanogenic, and archaeal
      community structures within these two types of wetland vegetation were studied by
      phylogenetic analysis targeting particulate methane monooxygenase (pmoA), methyl
      coenzyme M reductase (mcrA), and the archaeal 16S rRNA gene. The pmoA library
      indicated that Methylomonas and Methylocystis predominated in the Sphagnum
      covered and Sasa-invaded areas, respectively. The mcrA and 16S rRNA libraries
      indicated that Methanoregula were abundant methanogens in the Sphagnum-covered
      area. In the Sasa-invaded area, by contrast, mcrA genes were not detected, and no
      16S rRNA clones were affiliated with previously known methanogens. Because the
      Sasa-invaded area still produced methane, of the various uncultured populations
      detected, novel euryarchaeotal lineages are candidate methane producers.

PMID- 21897041
TI  - UVC mutagenicity is suppressed in Japanese miso-treated human RSa cells, possibly
      via GRP78 expression.
AB  - Little is known about the ability of miso, to modulate mutability in human cells.
      We have observed increased levels of glucose-regulated protein 78 (GRP78)
      expression in association with suppression of mutation in human RSa cells
      irradiated with ultraviolet C (UVC). Here we examined to determine whether miso
      treatment results in increased GRP78 expression and suppression of UVC
      mutagenicity in RSa cells. Supernatants of water extracts of miso products and
      their components were tested. In the sample-treated cells, the amount of GRP78,
      as estimated by RT-PCR and immunoblotting analysis, increased, and the UVC
      induced ouabain resistant mutation (Oua(R)) and the K-ras codon 12-base
      substitution mutation frequency decreased. This decrease was not observed in
      cells with downregulation of GRP78 by GRP78 siRNA transfection. The results
      suggest that miso suppresses UVC mutagenicity by increasing GRP78 expression in
      human cells.

PMID- 21897042
TI  - Grape seed procyanidin b2 inhibits human aortic smooth muscle cell proliferation
      and migration induced by advanced glycation end products.
AB  - Advanced glycation end product (AGE)-induced vascular smooth muscle cell (VSMC)
      proliferation is vital to the progression of diabetic vasculopathy. A grape seed
      procyanidin extract has been reported to possess anti-oxidative and anti
      inflammatory properties and to display a significant cardiovascular protective
      effect, but little is know about the underlying mechanism. The objective of this
      present study was to determine whether GSPB2 (grape seed procyanidin B2), which
      is a dimeric procyanidin and more biologically active, could inhibit AGE-induced
      VSMC proliferation by affecting the production of ubiquitin COOH-terminal
      hydrolase 1 (UCH-L1), the degradation of IkappaB-alpha and nuclear translocation
      of NF-kappaB in human aortic smooth muscle cells (HASMCs). Our data show that
      GSPB2 preincubation markedly inhibited AGE-induced proliferation and migration of
      HASMCs in a dose-dependent manner and upregulated the protein level of UCH-L1.
      Further studies revealed that the GSPB2 pretreatment markedly attenuated the
      degradation of IkappaB-alpha and nuclear translocation of NF-kappaB by modulating
      ubiquitination of IkappaB-alpha in AGE-exposed HASMCs. These results collectively
      suggest that AGE-induced HASMC proliferation and migration was suppressed by
      GSPB2 through regulating UCH-L1 and ubiquitination of IkappaB-alpha. GSPB2 may
      therefore have therapeutic potential in preventing and treating vascular
      complications of diabetes mellitus.

PMID- 21897043
TI  - Novel taxa-4(20),12-diene and 2(3->20)abeotaxane from needles of Taxus
      canadensis.
AB  - A novel 6/8/6-membered taxane with a rare C-12(13)-double bond and rare 2(3
      >20)abeotaxane were isolated from the needles of Taxus canadensis. Their
      structures were characterized as 7beta,9alpha,10beta-triacetoxytaxa-4(20),12
      diene-2alpha,5alpha,11beta-triol (1) and 2alpha,7beta,10beta-triacetoxy-5alpha
      hydroxy-2(3->20)abeotaxa-4(20),11-diene-9,13-dione (2) on the basis of 1D and 2D
      spectroscopic data. 1 is the first example of a natural taxane without
      substitution at both C-13 and C-14.

PMID- 21897044
TI  - Physiological and biochemical characterization of three nucleoside diphosphate
      kinase isozymes from rice (Oryza sativa L.).
AB  - Nucleoside diphosphate kinase (NDPK) is a ubiquitous enzyme that catalyzes the
      transfer of the gamma-phosphoryl group from a nucleoside triphosphate to a
      nucleoside diphosphate. In this study, we examined the subcellular localization,
      tissue-specific gene expression, and enzymatic characteristics of three rice NDPK
      isozymes (OsNDPK1-OsNDPK3). Sequence comparison of the three OsNDPKs suggested
      differential subcellular localization. Transient expression of green fluorescence
      protein-fused proteins in onion cells indicated that OsNDPK2 and OsNDPK3 are
      localized to plastid and mitochondria respectively, while OsNDPK1 is localized to
      the cytosol. Expression analysis indicated that all the OsNDPKs are expressed in
      the leaf, leaf sheath, and immature seeds, except for OsNDPK1, in the leaf
      sheath. Recombinant OsNDPK2 and OsNDPK3 showed lower optimum pH and higher
      stability under acidic pH than OsNDPK1. In ATP formation, all the OsNDPKs
      displayed lower K(m) values for the second substrate, ADP, than for the first
      substrate, NTP, and showed lowest and highest K(m) values for GTP and CTP
      respectively.

PMID- 21897045
TI  - The relationship between chromosomal positioning within the nucleus and the SSD1
      gene in Saccharomyces cerevisiae.
AB  - Eukaryotic cells are characterized by very large chromosomal DNAs efficiently
      packed within the nucleus. To identify the mechanism of chromosomal packaging
      based on the uniqueness of the centromere region in Saccharomyces cerevisiae, we
      isolated the HCH6 mutant, which shows 2.5-fold higher efficiency of site-specific
      recombination between the CEN5 and HIS3 loci than the wild-type CH53 strain. This
      mutant also displayed defects in cell integrity at high temperature. The SSD1
      gene was perhaps responsible for this defect. The efficiency of site-specific
      recombination was decreased by the introduction of SSD1 in HCH6 cells and
      increased by disruption of SSD1 in the wild-type cells. Furthermore, the
      distances between the CEN5 and HIS3 loci and between the CEN5 locus and the
      spindle pole body (SPB) indicated that disrupting SSD1 caused a loss of the
      anchoring of the CEN5 locus near SPB. These results suggest Ssd1p-dependent cross
      talk between chromosomal positioning within the nucleus and the positioning of
      cellular components within the cell.

PMID- 21897046
TI  - Formate oxidase, an enzyme of the glucose-methanol-choline oxidoreductase family,
      has a His-Arg pair and 8-formyl-FAD at the catalytic site.
AB  - Formate oxidase of Aspergillus oryzae RIB40 contains an 8-replaced FAD with
      molecular mass of 799 as cofactor. The 1H-NMR spectrum of the cofactor fraction
      obtained from the enzyme indicated that the 8-replaced FAD in the fraction was 8
      formyl-FAD, present in open form and hemiacetal form. The oxidation-reduction
      potentials of the open and hemiacetal forms were estimated by cyclic voltammetry
      to be -47 and -177 mV vs. Normal Hydrogen Electrode respectively. The structure
      of the enzyme was constructed using diffraction data to 2.24 A resolution
      collected from a crystal of the enzyme. His511 and Arg554 were situated close to
      the pyrimidine part of the isoalloxazine ring of 8-formyl-FAD in open form. The
      enzyme had 8-formyl-FAD, the oxidation potential of which was approximately 160
      mV more positive than that of FAD, and the His-Arg pair at the catalytic site,
      unlike the other enzymes belonging to the glucose-methanol-choline oxidoreductase
      family.

PMID- 21897047
TI  - Consumption of soy protein isolate reduces hepatic SREBP-1c and lipogenic gene
      expression in wild-type mice, but not in FXR-deficient mice.
AB  - We examined to determine whether hepatic gene expression is affected in mice in
      which blood lipid levels remain unchanged fed soy protein isolate (SPI) for a
      short time. We also examined SPI-mediated effects in farnesoid X receptor (FXR)
      deficient mice. Compared with casein, SPI affected the expression of various
      hepatic genes related to lipid metabolism in the wild-type mice. No effects of
      SPI were observed in the FXR-deficient mice, suggesting the importance of FXR.
      Hepatic peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC
      1alpha) gene expression was reduced by SPI, and this might be associated with a
      decrease in FXR expression. Decreased FXR led to decreased expression of its
      target, the bile-salt export pump necessary for bile acid secretion and dietary
      lipid absorption. The earliest response to SPI was a decrease in hepatic sterol
      regulatory element-binding protein (SREBP)-1c mRNA, on day 3. SPI activated
      hepatic adenosine monophosphate-activated protein kinase (AMPK), which can lead
      to a reduction in SREBP-1c mRNA. These data indicate the importance of SREBP-1c
      and PGC-1alpha/FXR in SPI-mediated alterations in hepatic gene expression.

PMID- 21897048
TI  - Anti-diabetic effects of a kaempferol glycoside-rich fraction from unripe soybean
      (Edamame, Glycine max L. Merrill. 'Jindai') leaves on KK-A(y) mice.
AB  - The anti-diabetic effects of a kaempferol glycoside-rich fraction (KG) prepared
      from leaves of unripe Jindai soybean (Edamame) and kaempferol, an aglycone of
      kaempferol glycoside, were determined in genetically type 2 diabetic KK-A(y)
      mice. The hemoglobin A(1c) level was decreased and tended to be decreased by
      respectively feeding KG and kaempferol (K). The area under the curve (AUC) in the
      oral glucose tolerance test (OGTT) tended to be decreased by feeding K and KG.
      The liver triglyceride level and fatty acid synthase activity were both decreased
      in the mice fed with KG and K when compared to those parameters in the control
      mice. These results suggest that KG and K would be useful to improve the diabetes
      condition. The major flavonoids in KG were identified as kaempferol 3-O-beta-D
      glucopyranosyl(1->2)-O-[alpha-L-rhamnopyranosyl(1->6)]-beta-D-galactopyranoside,
      kaempferol 3-O-beta-D-glucopyranosyl(1->2)-O-[alpha-L-rhamnopyranosyl(1->6)]-beta
      D-glucopyranoside, kaempferol 3-O-beta-D-(2-O-beta-D-glucopyranosyl)
      galactopyranoside and kaempferol 3-O-beta-D-(2,6-di-O-alpha-L-rhamnopyranosyl)
      galactopyronoside, suggesting that these compounds or some of them may be
      concerned with mitigation of diabetes.

PMID- 21897049
TI  - Larvicidal activity of (-)-dihydroguaiaretic acid derivatives against Culex
      pipiens.
AB  - The larvicidal activity against Culex pipiens of all stereoisomers of
      dihydroguaiaretic acid (DGA) and secoisolariciresinol was measured, and these
      DGAs were found to be potent. Sixteen (-)-DGA derivatives were then newly
      synthesized to analyze their structure-activity relationship. Two derivatives
      monohydroxylated at the 3- or 4-position of the 7-phenyl group of DGA induced
      acute paralytic activity in the mosquitoes. Derivatives with several hydroxyl
      groups had lower activity than the natural compound, suggesting that
      hydrophobicity was probably an important factor for their insecticidal activity.

PMID- 21897050
TI  - Depression by a green tea extract of alcohol-induced oxidative stress and
      lipogenesis in rat liver.
AB  - We determined the effects of a green tea extract with 36% alcohol on the blood
      alcohol content, oxidative stress, lipogenesis, inflammation and liver function
      of female Wistar rats. Tea alcohol significantly decreased the O2-, H2O2 and HOCl
      amounts via catechins and not caffeine. Thirty days of alcohol gavage improved
      the level of reactive oxygen species (ROS) in the liver, bile and blood,
      increased the 4-hydroxynonenal-protein adducts, Kupffer cell infiltration and
      lipid accumulation in the liver, and elevated the plasma alanine aminotransferase
      level. A western blot analysis showed reduced expression of the oxidative enzymes
      (CYP2E1 and NADPH oxidase p47phox protein) and lipogenic enzymes (SREBP-1c and
      fatty acid synthase) in the alcohol-treated liver. Tea alcohol significantly
      attenuated these elevated parameters. We conclude that the green tea extract in
      alcohol efficiently reduced the amounts of O2-, H2O2 and HOCl primarily due to
      the catechin content, and not caffeine. The developed tea liquor attenuated
      alcohol-induced oxidative injury and lipogenesis in the liver by the synergetic
      action of catechins and caffeine.

PMID- 21897051
TI  - Molecular-weight-dependent, anionic-substrate-preferential transport of beta
      lactam antibiotics via multidrug resistance-associated protein 4.
AB  - beta-Lactam antibiotics have cerebral and peripheral adverse effects. Multidrug
      resistance-associated protein 4 (MRP4) has been reported to transport several
      beta-lactam antibiotics, and its expression at the blood-brain barrier also
      serves to limit their distribution to the brain. Therefore, the purpose of this
      study was to clarify the structure-activity relationship of MRP4-mediated
      transport of beta-lactam antibiotics using MRP4-expressing Sf9 membrane vesicles.
      The transport activity was evaluated as MRP4-mediated transport per MRP4 protein
      [nL/(min.fmol MRP4 protein)] based on measurement of MRP4 protein expression by
      means of liquid chromatography-tandem mass spectrometry. Cefotiam showed the
      greatest MRP4-mediated transport activity [8.90 nL/(min.fmol MRP4 protein)] among
      the beta-lactam antibiotics examined in this study. Measurements of differential
      transport activity of MRP4 for various beta-lactam antibiotics indicated that (i)
      cephalosporins were transported via MRP4 at a greater rate than were penams, beta
      lactamase inhibitors, penems, or monobactams; (ii) MRP4-mediated transport
      activity of anionic cephalosporins was greater than that of zwitterionic
      cephalosporins; and (iii) higher-molecular-weight anionic beta-lactam antibiotics
      showed greater MRP4-mediated transport activity than lower-molecular-weight ones,
      whereas zwitterionic beta-lactam antibiotics did not show molecular weight
      dependency of MRP4-mediated transport. These quantitative data should prove
      useful for understanding MRP-related adverse effects of beta-lactam antibiotics
      and their derivatives.

PMID- 21897052
TI  - Bridging from preclinical to clinical studies for tyrosine kinase inhibitors
      based on pharmacokinetics/pharmacodynamics and toxicokinetics/toxicodynamics.
AB  - The purpose of this study was to provide a pharmacokinetics/pharmacodynamics and
      toxicokinetics/toxicodynamics bridging of kinase inhibitors by identifying the
      relationship between their clinical and preclinical (rat, dog, and monkey) data
      on exposure and efficacy/toxicity. For the eight kinase inhibitors approved in
      Japan (imatinib, gefitinib, erlotinib, sorafenib, sunitinib, nilotinib,
      dasatinib, and lapatinib), the human unbound area under the concentration-time
      curve at steady state (AUC(ss,u)) at the clinical dose correlated well with
      animal AUC(ss,u) at the no-observed-adverse-effect level (NOAEL) or maximum
      tolerated dose (MTD). The best correlation was observed for rat AUC(ss,u) at the
      MTD (p < 0.001). E(max) model analysis was performed using the efficacy of each
      drug in xenograft mice, and the efficacy at the human AUC of the clinical dose
      was evaluated. The predicted efficacy at the human AUC of the clinical dose
      varied from far below E(max) to around E(max) even in the tumor for which use of
      the drugs had been accepted. These results suggest that rat AUC(ss,u) at the MTD,
      but not the efficacy in xenograft mice, may be a useful parameter to estimate the
      human clinical dose of kinase inhibitors, which seems to be currently determined
      by toxicity rather than efficacy.

PMID- 21897053
TI  - Dopamine D(1) receptors participate in cocaine-induced place preference via
      regulation of ryanodine receptor expression.
AB  - Ryanodine receptors (RyRs) with three different isoforms in the brain play a role
      to facilitate Ca(2+) release from the intracellular Ca(2+) pool. Although cocaine
      is a strongly addictive psychostimulant that dramatically affects the central
      nervous system function, the role of RyRs and regulation of their expression by
      cocaine-induced place preference have not yet been defined well. The present
      study investigated the regulation of RyR expression in mice under intermittent
      cocaine treatment using the place preference procedure. The cocaine-induced place
      preference was inhibited by intracerebroventricular pretreatment with dantrolene,
      a RyRs antagonist, in a dose-dependent manner. The levels of RyR-1 and -2 in the
      limbic forebrain and frontal cortex significantly increased in the cocaine
      conditioned mice, whereas that of RyR-3 in these two brain regions showed no
      changes. Although the up-regulation of RyRs was not affected by blockade of L
      type voltage-gated calcium channels, the increase of RyR-1 and -2 in the limbic
      forebrain and frontal cortex was completely abolished by SCH23390, a selective
      antagonist of dopamine D(1) receptors, but not by sulpiride, a selective
      antagonist of dopamine D(2) receptors. These findings indicate that RyRs play a
      critical role in the development of cocaine-induced place preference and that the
      up-regulation of RyRs in the brain of a mouse showing cocaine-induced place
      preference is regulated by dopamine D(1) receptors.

PMID- 21897054
TI  - Comparison of injuring effects of vesicant, irritant, and nonvesicant anticancer
      drugs on endothelial cells.
AB  - Anticancer drugs are classified as vesicant, irritant, and nonvesicant drugs on
      the basis of frequency of their vascular disorder. In this study, we compared the
      injuring effects of three typical anticancer drugs of each class on porcine aorta
      endothelial cells (PAECs). The concentration inducing 50% cell viability
      inhibition was lower in the order of vesicant, irritant, and nonvesicant drugs.
      These results suggest that injuring effects of anticancer drugs on PAECs may be
      relevant as an indicator of frequency of their vascular disorder, and that this
      experimental model may be useful for the study of vascular disorder.

PMID- 21897056
TI  - Comparison of peripheral neuropathy induced by standard and nanoparticle albumin
      bound paclitaxel in rats.
AB  - Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is delivered to tumors and
      increases antitumor activity compared with solvent-based paclitaxel. However, in
      a clinical trial, higher and lower rates of peripheral neuropathy and neutropenia
      were observed. In this study, we compared the effects of nab-paclitaxel and
      standard paclitaxel on pain behaviors in rats. Repeated administration of nab
      paclitaxel dose-dependently induced both mechanical and cold allodynia, and the
      effects of nab-paclitaxel on pain behaviors tended to be stronger than that of
      standard paclitaxel at the doses used clinically. These results suggest that
      closer attention must be paid to the neuropathy when administering nab-paclitaxel
      in clinical settings.

PMID- 21897055
TI  - Effect of efonidipine on TGF-beta1-induced cardiac fibrosis through Smad2
      dependent pathway in rat cardiac fibroblasts.
AB  - Transforming growth factor beta-1 (TGF-beta1) plays a critical role in
      progression of cardiac fibrosis, which may involve intracellular calcium change.
      We examined effects of efonidipine, a dual T-type and L-type calcium channel
      blocker (CCB), on TGF-beta1-induced fibrotic changes in neonatal rat cardiac
      fibroblast. T-type and L-type calcium channel mRNAs were highly expressed in
      cultured cardiac fibroblasts. TGF-beta1 (5 ng/mL) significantly increased Smad2
      phosphorylation and [(3)H]-leucine incorporation, which were attenuated by
      pretreatment with efonidipine (10 uM). Neither R(-)efonidipine (10 uM), selective
      T-type CCB, nor nifedipine (10 uM), selective L-type CCB, efficaciously inhibited
      both TGF-beta1-induced Smad2 phosphorylation and [(3)H]-leucine incorporation.
      However, both were markedly attenuated by combination of R(-)efonidipine and
      nifedipine, EDTA, or calcium-free medium. Pretreatment with Smad2 siRNA
      significantly attenuated [(3)H]-leucine incorporation induced by TGF-beta1. These
      data suggest that efonidipine elicits inhibitory effects on TGF-beta1- and Smad2
      dependent protein synthesis through both T-type and L-type calcium channel
      blocking actions in cardiac fibroblasts.

PMID- 21897057
TI  - Role of acidification elicited by sialylation and sulfation of zona glycoproteins
      during oocyte maturation in porcine sperm-zona pellucida interactions.
AB  - The porcine zona pellucida (ZP) undergoes biochemical changes during the final
      phase of maturation prior to fertilization. The present study was conducted to
      elucidate whether the acidification of ZP glycoproteins during porcine oocyte
      maturation influences sperm-ZP interactions. Two-dimensional gel electrophoresis
      clearly demonstrated that ZP acidification occurred in accordance with the
      sialylation and sulfation of ZP glycoproteins in oocytes matured for 44 h. The
      increases in the incidences of sperm penetration and polyspermy with the progress
      of the IVM culture period were significantly suppressed by ZP desialylation on
      treatment with neuraminidase as a consequence of reductions in the number of
      sperm bound to ZPs and the acrosome reaction (AR) in ZP-bound sperm (P<0.05). In
      contrast, the blocking of ZP sulfation by NaClO(3) treatment during IVM markedly
      reduced the incidence of polyspermy with no inhibitory effect on penetration, but
      the number of sperm bound to ZPs and the rate of AR-inducing sperm were decreased
      to the same level as in desialylated oocytes. The results indicate that ZP
      sulfation influences sperm-ZP interactions in a ZP sialylation-independent
      manner. Moreover, sialylation and sulfation were not associated with a protective
      proteolytic modification of the ZP matrix before fertilization. These findings
      suggest that ZP acidification elicited by the sialylation and sulfation of ZP
      glycoproteins during oocyte maturation contributes to the porcine ZP acquiring
      the capacity to accept sperm.

PMID- 21897058
TI  - The positive effects of seminal plasma during the freezing process on
      cryosurvival of sperm with poor freezability in the rhesus macaque (Macaca
      mulatta).
AB  - The objective was to examine the effect of seminal plasma on cryopreservation of
      sperm from rhesus macaques. Sperm cryosurvival was evaluated by sperm motility
      and acrosomal integrity. Compared with slow cooling (-0.4 C/min) from 37 C (body
      temperature) to 4 C, rapid cooling (-16 C/min) caused cold shock in rhesus
      macaque sperm. The cryosurvival of sperm was decreased regardless of the presence
      or absence of seminal plasma (P<0.05). However, the presence of seminal plasma
      during cold shock at a rapid cooling rate improved sperm motility and acrosomal
      integrity in individual monkeys. Male-to-male variation in sperm cryosurvival was
      observed after cryopreservation (P<0.05), and the presence of seminal plasma
      during sperm cryopreservation improved sperm motility and acrosomal integrity in
      individual monkeys (P<0.05). Furthermore, by adding seminal plasma from monkeys
      with good sperm cryosurvival to sperm freezing extender, the frozen-thawed
      motility and acrosomal integrity of sperm from monkey with poor cryosurvival were
      improved (P<0.05). The present study indicated that seminal fluid is beneficial
      to sperm undergoing cold shock or cryopreservation in individual monkeys. The
      cryosurvival of sperm from rhesus macaques with poor sperm freezability could be
      improved by the presence of seminal plasma from males with good sperm
      cryosurvival. This finding provides a useful method for genetic preservation in
      this important species.

PMID- 21897059
TI  - Genome-wide transcript expression analysis in the uterovaginal junction in
      association with fertile period in Tsaiya ducks.
AB  - We performed the first genome-wide expression analysis to compare the differences
      in gene expression in the female sperm reservoir of the duck reproductive tract
      between two groups with long and short fertile periods to identify factors that
      may be associated with the fertile period using an oligonucleotide microarray.
      RNA was extracted from the uterovaginal junction (UV junction) of the two groups.
      Affymetrix chips containing comprehensive coverage of 32773 transcripts were
      hybridized with biotin-labeled cRNA, and three biological repeats were performed.
      We identified 27 transcripts as being differentially regulated. Interestingly, by
      mapping the differentially expressed transcripts to annotated pathways, we found
      that Neuropeptide Y (NPY), the RNA expression of which was increased by 2.96-fold
      in the short-fertile-period group as compared with the long-fertile-period group
      in our experiment, has been shown to reduce blood flow and substance supply to
      local tissues. Enah/Vasp-like (EVL), the RNA expression of which was
      significantly increased by 1.77-fold in the short-fertile-period group as
      compared with the long-period group, has been demonstrated to be important in
      activated T-cells. In contrast, trafficking kinesin-binding protein 1 (TRAK1),
      the expression of which was increased by 2.33-fold in the long-period group as
      compared with its counterparts, has been suggested to inhibit precocious
      activation of sperm and prolong sperm life in the female sperm reservoir. The
      results of real-time PCR confirmed the data obtained by microarray analysis. Our
      study demonstrated that combining global gene expression investigation with
      annotated pathway resources contributes to the understanding of sperm life when
      sustained in the UV junction.

PMID- 21897060
TI  - A retrospective study of inflammatory colorectal polyps in miniature dachshunds.
AB  - Medical records of dogs with colorectal polyps were retrospectively reviewed, and
      clinical presentation of inflammatory colorectal polyps in miniature dachshunds
      was evaluated. Of 33 dogs found to have colorectal polyps, miniature dachshunds
      were markedly over-represented with 16 dogs (48%), of which 12 (75%) were found
      to have inflammatory polyps. Multiple polyps localized between the rectum and the
      descending colon was the most common finding in miniature dachshunds with
      inflammatory polyps. Twenty dogs (80%) out of 25 miniature dachshunds with
      inflammatory colorectal polyps responded to immunosuppressive therapy using
      prednisolone and cyclosporine. The results of this study indicate that miniature
      dachshunds are predisposed to develop inflammatory colorectal multiple polyps,
      for which immunosuppressive therapy may be a treatment option.

PMID- 21897061
TI  - Computed tomography and radiographic lymphography of the thoracic duct by
      subcutaneous or submucosal injection.
AB  - A simple method of lymphography of the thoracic duct was investigated. Using
      three female beagles, contrast media were administered rectally, vaginally and
      into the perianal tissue. The administration sites were gently massaged, and
      imaging was carried out at constant intervals using computed tomography and
      radiograph. Moreover, Indian ink was administered into the rectum mucous membrane
      in dogs for proof of this method of lymphography, and the lymph drainage routes
      were observed. The investigation showed that clear computed tomography and
      radiographic contrast images of the thoracic duct were obtained by subcutaneous
      and submucosa injection of angiography contrast medium and 3D processing of these
      images revealed the three-dimensional positions and course of the thoracic duct
      and cisterna chyli.

PMID- 21897062
TI  - Effect of cooled and chlorinated chiller water on Campylobacter and coliform
      counts on broiler carcasses during chilling at a middle-size poultry processing
      plant.
AB  - To evaluate the effect of cooled and chlorinated chill water for Campylobacter
      and coliforms at a middle-size processing plant which was considered to be
      difficult for eliminate pathogenic bacteria on carcasses, following three
      conditions were examined; keeping temperature at < 20, < 10 and < 10 degrees C,
      and chlorine concentration at < 50, < 50 and 50 to 70 ppm during processing in
      experiment 1, 2 and 3 respectively. Fifteen prechill and 15 postchill carcasses
      were examined in each experiment. In lower temperature of experiment 2,
      decreasing rate (%) of coliforms was significantly higher (P<0.01) than that in
      experiment 1. In higher chlorination of experiment 3, no Campylobacter was
      detected from all postchill carcasses.

PMID- 21897063
TI  - [Current status in and future directions of the treatment of hematological
      disorders with molecular-targeting agents--Overview].

PMID- 21897064
TI  - [Current treatment strategies with novel agents for multiple myeloma].

PMID- 21897065
TI  - [Development of novel agents for multiple myeloma; now and the future].

PMID- 21897066
TI  - [Present status and perspective of targeted therapy for B-cell lymphoma].

PMID- 21897067
TI  - [Novel monoclonal antibodies for the treatment of malignant lymphomas].

PMID- 21897068
TI  - [Management of refractory ITP with thrombopoietin receptor agonists].

PMID- 21897069
TI  - [Progress in the management of paroxysmal nocturnal hemoglobinuria by
      eculizumab].

PMID- 21897070
TI  - [Comparison of post-remission strategies in elderly patients with acute myeloid
      leukemia in first complete remission].

PMID- 21897071
TI  - [Bone marrow findings of childhood aplastic anemia: analyses of 140 cases by
      central reviewers].
AB  - The revised WHO classification proposed the term "refractory cytopenia of
      childhood (RCC)" for children with myelodysplastic syndrome (MDS) with a low
      blast count. The differential diagnosis between RCC and aplastic anemia (AA) is
      challenging, especially when bone marrow is hypoplastic and there is no
      detectable chromosomal abnormality. To reveal the difference between AA and RCC
      with respect to the clinical and biological features, we retrospectively reviewed
      the bone marrow smears of 140 patients registered for childhood AA-97 study,
      which were classified into three groups as follows; the AA group was defined as
      having no morphologically dysplastic changes; the AA-RCC borderline group was
      defined as having <10% dysplastic changes in the erythroid lineage only; and the
      RCC group was defined as having dysplastic changes in more than two cell lineages
      or >10% in a single cell lineage. The patients were classified into the AA group
      (n=96, 69%), AA-RCC borderline group (n=20, 14%) and RCC group (n=24, 17%). Most
      of the patients in the AA group were classified as having very severe disease,
      whereas most of the patients in the RCC group were classified as non-severe
      disease. Only 2 patients in the AA group developed acute myeloid leukemia. The
      response rate to immunosuppressive therapy did not differ among the 3 groups. To
      demonstrate whether the two diseases are truly different entities, it is
      necessary to compare molecular backgrounds between the AA and RCC groups.

PMID- 21897072
TI  - [Predictive factors for the complication of allogeneic stem cell
      transplantation].

PMID- 21897073
TI  - [Significance of intensified conditioning regimen for allogeneic hematopoietic
      stem cell transplantation for treatment of acute leukemias].

PMID- 21897074
TI  - [Conditioning regimen of allogeneic hematopoietic stem cell transplantation for
      aplastic anemia in Japan].

PMID- 21897075
TI  - [Molecular mechanisms of leukemogenesis in MLL-leukemias].

PMID- 21897076
TI  - [Role of TEL gene alterations in childhood leukemias].

PMID- 21897077
TI  - [Leukemogenesis caused by dysfunctions of GATA1 transcription factor].

PMID- 21897078
TI  - [Clinical analysis of 3 cases with primary splenic diffuse large B-cell
      lymphoma].
AB  - The definition of primary splenic lymphoma is controversial, but it has been
      reported to be a rare disease that comprises less than 1% of all malignant
      lymphomas. Three cases of primary splenic diffuse large B-cell lymphoma treated
      at our institution are described here. Median follow-up was 34.6 months (range
      8.7~39.2) and median age at diagnosis was 72 years old (range 65~73). In all
      three cases, the diagnosis was definitively established not by splenectomy but by
      ultrasonically guided percutaneous splenic tissue core biopsy. Using the Hans
      classifier, one of the cases was subclassified as the germinal center B-cell like
      (GCB) subtype and two as non-GCB subtype. One case was CD5-positive diffuse large
      B-cell lymphoma. Two patients were in Ann Arbor stage II and one was in stage
      III. Using the International Prognostic Index, one was categorized as
      Low/intermediate risk, one as high/intermediate risk, and one as high risk. All
      patients underwent eight cycles of rituximab plus cyclophosphamide, doxorubicin,
      vincristine and prednisolone followed by irradiation therapy. These three
      patients attained complete response. Although the follow-up period to date has
      been short, all patients have maintained a complete response and are currently
      alive. To determine whether our management protocol is valid, further
      observations are needed.

PMID- 21897079
TI  - [Glossitis by mixed infection of cytomegalovirus and herpes simplex virus during
      therapy for pure red cell aplasia complicated with Good syndrome].
AB  - A 64-year-old man with a 10-year history of Good syndrome had been treated with
      periodic replacement of gamma-globulin. He also had a 6-year history of lichen
      planus of the tongue. In 2009, the patient was diagnosed as having pure red cell
      aplasia (PRCA) based on bone marrow aspiration. Thymectomy was not effective.
      Then, immunosuppressive therapy with PSL and cyclosporine was initiated. Twenty
      days after treatment painful ulcer appeared on the left side of the tongue.
      Biopsy specimen of the ulcer demonstrated cells infected with cytomegalovirus and
      herpes simplex virus. Cytomegalovirus antigenemia was also positive. The tongue
      ulcer promptly improved after gancyclovir administration for a few weeks. Viral
      glossitis should be considered as part of the differential diagnoses of oral
      lesions not only in patients with HIV infection but also in those under
      immunosuppressive therapy.

PMID- 21897081
TI  - [Epidural abscess in the spine extended from pulmonary zygomycosis during
      consolidation chemotherapy for acute lymphoblastic leukemia].
AB  - A 37-year-old woman with acute lymphoblastic leukemia developed fever and
      pneumonia during persistent neutropenia after consolidation chemotherapy.
      Pneumonia was rapidly followed by the formation of abscess in adjacent
      subcutaneous tissues, muscles and bones. She subsequently developed sudden onset
      of paraplegia and loss of all sensation below Th4. Epidural abscess was detected
      by MRI. Emergency drainage was performed, but the patient died 4 days after the
      operation. Rhizopus oryzae grew from culture of the epidural abscess. Since the
      incidence of zygomycosis appears to have increased over the recent years,
      clinicians should be aware of the possibility of zygomycosis in case of any
      infection that is resistant to antibiotics.

PMID- 21897080
TI  - [Successful completion of left total hip arthroplasty by inhibitor neutralization
      therapy in a hemophilia B patient with high responding inhibitor].
AB  - Major surgery in hemophilia patients has been facilitated by the development of
      coagulation concentrates. However, it is still difficult to manage bleeding
      during major surgery in patients with inhibitors to FVIII/IX. In addition, there
      have been few reports of major surgery in hemophilia B with high responding
      inhibitors. We report a 26-year-old hemophilia B patient with high responding
      factor IX inhibitor who demonstrated severe hemophiliac arthropathy in his left
      hip joint. Total hip arthroplasty was performed with a high dose of FIX followed
      by recombinant FVIIa. His inhibitor titer was decreased from 111 BU/ml to 1.0
      BU/ml at surgery by avoiding the use of FIX concentrates. Thus, we could use high
      dose FIX for the management of surgical bleeding. Anamnestic response occurred on
      the 7th day after surgery and FIX concentrates were switched to recombinant
      FVIIa. The whole process was safely managed without any excess bleeding or
      adverse effects. The successful use of high dose FIX followed by recombinant
      FVIIa suggests that even major surgery could be safely performed in hemophilia B
      patients with a low titer of high responding inhibitors.

PMID- 21897082
TI  - Embryonic developmental patterns and energy expenditure are affected by
      incubation temperature in wood ducks (Aix sponsa).
AB  - Recent research in birds has demonstrated that incubation temperature influences
      a suite of traits important for hatchling development and survival. We explored a
      possible mechanism for the effects on hatchling quality by determining whether
      incubation temperature influences embryonic energy expenditure of wood ducks (Aix
      sponsa). Because avian embryos are ectothermic, we hypothesized that eggs
      incubated at higher temperatures would have greater energy expenditure at any
      given day of incubation. However, because eggs incubated at lower temperatures
      take longer to hatch than embryos incubated at higher temperatures, we
      hypothesized that the former would expend more energy during incubation. We
      incubated eggs at three temperatures (35.0 degrees , 35.9 degrees , and 37.0
      degrees C) that fall within the range of temperatures of naturally incubated wood
      duck nests. We then measured the respiration of embryos every 3 d during
      incubation, immediately after ducks externally pipped, and immediately after
      hatching. As predicted, embryos incubated at the highest temperature had the
      highest metabolic rates on most days of incubation, and they exhibited faster
      rates of development. Yet, because of greater energy expended during the hatching
      process, embryos incubated at the lowest temperature expended 20%-37% more energy
      during incubation than did embryos incubated at the higher temperatures. Slower
      developmental rates and greater embryonic energy expenditure of embryos incubated
      at the lowest temperature could contribute to their poor physiological
      performance as ducklings compared with ducklings that hatch from eggs incubated
      at higher temperatures.

PMID- 21897083
TI  - A physiological perspective on nectar-feeding adaptation in phyllostomid bats.
AB  - Nectar-feeding animals increase their food intake when nectar sugar concentration
      decreases. However, some species present physiological constraints that limit
      their energy intake when nectar is diluted. We hypothesized that gut capacities
      of bats affect the ability of these animals to acquire and store energy,
      modifying how they use food resources in the field. We measured the food intake
      and changes in body mass of the members of an assemblage of nectar-feeding bats
      (Choeronycteris mexicana, Leptonycteris yerbabuenae, and Glossophaga soricina)
      feeding on sucrose solutions of different concentrations (146, 292, 438, 584,
      730, 876, and 1,022 mmol L(-1)). The three bat species presented differences in
      their food intake and their capacity to store energy. While C. mexicana was able
      to maintain a constant energy intake at all concentrations tested, G. soricina
      and L. yerbabuenae decreased their sugar/energy intake at the lowest sugar
      concentrations. Choeronycteris mexicana also increased body mass independent of
      sugar concentration, while G. soricina and L. yerbabuenae did not. On the basis
      of our results, we generated a model relating gut capacities and the use of food
      resources in the field. Our model's predictions and field data support the idea
      that digestive traits affect the way these animals use the food resources present
      in their environment.

PMID- 21897084
TI  - Mitochondrial metabolic suppression in fasting and daily torpor: consequences for
      reactive oxygen species production.
AB  - Abstract Daily torpor results in an ~70% decrease in metabolic rate (MR) and a
      20%-70% decrease in state 3 (phosphorylating) respiration rate of isolated liver
      mitochondria in both dwarf Siberian hamsters and mice even when measured at 37
      degrees C. This study investigated whether mitochondrial metabolic suppression
      also occurs in these species during euthermic fasting, when MR decreases
      significantly but torpor is not observed. State 3 respiration rate measured at 37
      degrees C was 20%-30% lower in euthermic fasted animals when glutamate but not
      succinate was used as a substrate. This suggests that electron transport chain
      complex I is inhibited during fasting. We also investigated whether mitochondrial
      metabolic suppression alters mitochondrial reactive oxygen species (ROS)
      production. In both torpor and euthermic fasting, ROS production (measured as
      H(2)O(2) release rate) was lower with glutamate in the presence (but not absence)
      of rotenone when measured at 37 degrees C, likely reflecting inhibition at or
      upstream of the complex I ROS-producing site. ROS production with succinate (with
      rotenone) increased in torpor but not euthermic fasting, reflecting complex II
      inhibition during torpor only. Finally, mitochondrial ROS production was twofold
      more temperature sensitive than mitochondrial respiration (as reflected by Q(10)
      values). These data suggest that electron leak from the mitochondrial electron
      transport chain, which leads to ROS production, is avoided more efficiently at
      the lower body temperatures experienced during torpor.

PMID- 21897085
TI  - Reactive oxygen species and the regulation of hyperproliferation in a colonial
      hydroid.
AB  - Colonies of Podocoryna carnea circulate gastrovascular fluid among polyps via
      tubelike stolons. At polyp-stolon junctions, mitochondrion-rich cells in part
      regulate this gastrovascular flow. During competition, colonies hyperproliferate
      nematocytes and stolons; nematocysts are discharged until one colony is killed.
      Hyperproliferation then ceases, and normal growth resumes. Here, competing
      colonies were treated with azide, which inhibits respiration and upregulates
      reactive oxygen species (ROS). After the cessation of competition, azide-treated
      colonies continued to hyperproliferate. In azide-treated competing colonies,
      however, mitochondrion-rich cells were found to produce similar amounts of ROS as
      those in untreated competing colonies. Subsequent experiments showed that both
      azide treatment and competition diminished the lumen widths at polyp-stolon
      junctions, where mitochondrion-rich cells are found. In competing colonies, these
      diminished widths may also diminish the metabolic demand on these cells, causing
      mitochondria to enter the resting state and emit more ROS. Indeed, results with
      two fluorescent probes show that mitochondrion-rich cells in competing colonies
      produce more ROS than those in noncompeting colonies. In sum, these results
      suggest that competition perturbs the usual activity of mitochondrion-rich cells,
      altering their redox state and increasing ROS formation. Via uncharacterized
      pathways, these ROS may contribute to hyperproliferation.

PMID- 21897086
TI  - Decreasing urea?trimethylamine N-oxide ratios with depth in chondrichthyes: a
      physiological depth limit?
AB  - In marine osmoconformers, cells use organic osmolytes to maintain osmotic balance
      with seawater. High levels of urea are utilized in chondrichthyans (sharks, rays,
      skates, and chimaeras) for this purpose. Because of urea's perturbing nature,
      cells also accumulate counteracting methylamines, such as trimethylamine N-oxide
      (TMAO), at about a 2?1 urea?methylamine ratio, the most thermodynamically
      favorable mixture for protein stabilization, in shallow species. However,
      previous work on deep-sea teleosts (15 species) and chondrichthyans (three
      species) found an increase in muscle TMAO content and a decrease in urea content
      in chondrichthyans with depth. We hypothesized that TMAO counteracts protein
      destabilization resulting from hydrostatic pressure, as is demonstrated in vitro.
      Chondrichthyans are almost absent below 3,000 m, and we hypothesized that a
      limitation in urea excretion and/or TMAO retention might play a role. To test
      this, we measured the content of major organic osmolytes in white muscle of 13
      chondrichthyan species caught with along-contour trawls at depths of 50-3,000 m;
      the deepest species caught was from 2,165 m. Urea and TMAO contents changed
      significantly with depth, with urea?TMAO declining from 2.96 in the shallowest
      (50-90 m) groups to 0.67 in the deepest (1,911-2,165 m) groups. Urea content was
      291-371 mmol/kg in the shallowest group and 170-189 mmol/kg in the deepest group,
      declining linearly with depth and showing no plateau. TMAO content was 85-168
      mmol/kg in the shallowest group and 250-289 mmol/kg in the deepest groups. With
      data from a previous study for a skate at 2,850 m included, a second-order
      polynomial fit suggested a plateau at the greatest depths. When data for skates
      (Rajidae) were analyzed separately, a sigmoidal fit was suggested. Thus, the
      deepest chondrichthyans may be unable to accumulate sufficient TMAO to counteract
      pressure; however, deeper-living specimens are needed to fully test this
      hypothesis.

PMID- 21897087
TI  - A mass balance approach to identify and compare differential routing of 13C
      labeled carbohydrates, lipids, and proteins in vivo.
AB  - All animals route assimilated nutrients to their tissues where they are used to
      support growth or are oxidized for energy. These nutrients are probably not
      allocated homogeneously among the various tissue and are more likely to be
      preferentially routed toward some tissues and away from others. Here we introduce
      an approach that allows researchers to identify and compare nutrient routing
      among different organs and tissues. We tested this approach by examining nutrient
      routing in birds. House sparrows Passer domesticus were fed a meal supplemented
      with one of seven (13)C-labeled metabolic tracers representing three major
      classes of macronutrients, namely, carbohydrates, amino acids, and fatty acids.
      While these birds became postabsorptive (2 h after feeding), we quantified the
      isotopic enrichment of the lean and lipid fractions of several organs and
      tissues. We then compared the actual (13)C enrichment of various tissue fractions
      with the predictions of our model to identify instances where nutrients were
      differentially routed and found that different classes of macronutrients are
      uniquely routed throughout the body. Recently ingested amino acids were
      preferentially routed to the lean fraction of the liver, whereas exogenous
      carbohydrates were routed to the brain and the lipid fraction of the liver. Fatty
      acids were definitively routed to the heart and the liver, although high levels
      of palmitic acid were also recovered in the adipose tissue. Tracers belonging to
      the same class of molecules were not always routed identically, illustrating how
      this technique is also suited to examine differences in nonoxidative fates of
      closely related molecules. Overall, this general approach allows researchers to
      test heretofore unexamined predictions about how animals allocate the nutrients
      they ingest.

PMID- 21897088
TI  - Using a priori contrasts for multivariate repeated-measures ANOVA to analyze
      thermoregulatory responses of the dibbler (Parantechinus apicalis; Marsupialia,
      Dasyuridae).
AB  - Physiological studies often involve the repeated measurement of individuals over
      a range of ordered categorical conditions, for example, varying ambient
      temperature. We illustrate here the use of a priori contrasts for multivariate
      repeated-measures ANOVA by analyzing the thermal responses of various
      physiological variables for a small marsupial, the dibbler (Parantechinus
      apicalis). Our analyses showed that dibblers conform closely to the Scholander
      Irving model of endothermy. Body temperature was constant at low air
      temperatures, was 36.3 +/- 0.24 degrees C at thermoneutrality (30 degrees C), and
      increased at 35 degrees C. Metabolic rate decreased with increasing ambient
      temperature to a basal rate of 0.619 +/- 0.036 mL O(2) g(-1) h(-1) at 30 degrees
      C; it extrapolated closely to thermoneutral body temperature. Increased oxygen
      demand at lower ambient temperature was met by increased respiratory minute
      volume, achieved by increased respiratory frequency and tidal volume; oxygen
      extraction was constant at about 19%. Evaporative water loss and wet and dry
      thermal conductance increased markedly at high ambient temperatures but not
      sufficiently to maintain constant body temperature. Relative water economy was
      similar to that of other small marsupials, increasing linearly at lower air
      temperatures with a point of relative water economy of 20.3 degrees C. We
      conclude that a priori contrasts provide a statistically appropriate and powerful
      analysis that can be used routinely to statistically describe the pattern of
      response of physiological variables to a categorical factor and are especially
      useful for repeated-measures ANOVA designs common to many physiological studies.

PMID- 21897089
TI  - The regulation index: a new method for assessing the relationship between oxygen
      consumption and environmental oxygen.
AB  - Critical oxygen pressure (P(C)) is used in respiratory physiology to measure the
      response to hypoxia. P(C) defines the partial pressure of oxygen (Po(2)) at which
      an oxygen regulator switches to a conformer. However, not all animals show such
      clear patterns in oxygen consumption rate (Mo2), and there are many methods for
      determining P(C). This study assesses two methods that determine regulatory
      ability and four that calculate P(C). A new method, the regulation index (RI),
      assigns to an animal a relative measure of regulatory ability by calculating the
      area under the Mo2 versus Po(2) curve that is greater than a linear trend. The
      six methods are applied to developmental Mo2 data of two amphibians, Pseudophryne
      bibronii and Crinia georgiana. The four methods used to determine P(C) produced
      similar results but failed to identify the increase in regulation on hatching in
      C. georgiana or the greater regulation in larval C. georgiana compared with P.
      bibronii. Of the two methods that evaluated regulation, only the RI
      satisfactorily represented the entire range of Po(2). The RI is advantageous
      because it has clearly defined limits and does not constrain data to fit any
      single pattern. The RI can be used in concert with P(C), which can be easily
      calculated during the RI analysis, to provide a clearer definition of the Mo2
      response to environmental Po(2).

PMID- 21897091
TI  - Cytotoxicity of gamma-ray in rat immature hippocampal neurons.
AB  - This in vitro study evaluated the detrimental effect of acute gamma (gamma)
      irradiation on rat immature hippocampal neurons. Rat immature hippocampal neurons
      (0.5 day in vitro) were irradiated with 0~4 Gy gamma-rays. Cytotoxicity was
      analyzed using a lactate dehydrogenase release assay at 24 h after gamma
      irradiation. Radiation-induced cytotoxicity in immature hippocampal neurons
      increased in a dose-dependent manner. Pre-treatments of pro-apoptotic caspase
      inhibitors and anti-oxidative substances significantly blocked gamma-irradiation
      induced cytotoxicity in immature hippocampal neurons. The results suggest that
      the caspase-dependent cytotoxicity of gamma-rays in immature hippocampal cultured
      neurons may be caused by oxidative stress.

PMID- 21897092
TI  - Multidetector computed tomographic angiography evaluation of micropig major
      systemic vessels for xenotransplantation.
AB  - Due primarily to the increasing shortage of allogeneic donor organs,
      xenotransplantation has become the focus of a growing field of research.
      Currently, micropigs are the most suitable donor animal for humans. However, no
      standard method has been developed to evaluate the systemic vascular anatomy of
      micropigs and standard reference values to aid in the selection of normal healthy
      animals as potential organ donors are lacking. Using 64-channel multidetector row
      computed tomographic angiography (MDCTA), we evaluated morphological features of
      the major systemic vessels in micropigs and compared our results to published
      human data. The main vasculature of the animals was similar to that of humans,
      except for the iliac arterial system. However, diameters of the major systemic
      vessels were significantly different between micropigs and humans. Specifically,
      the diameter of the aortic arch, abdominal aorta, external iliac artery, and
      femoral artery, were measured as 1.50 +/- 0.07 cm, 0.85 +/- 0.06 cm, 0.52 +/-
      0.05 cm, and 0.48 +/- 0.05 cm, respectively, in the micropigs. This MDCTA data
      for micropig major systemic vessels can be used as standard reference values for
      xenotransplantation studies. The use of 64-channel MDCTA enables accurate
      evaluation of the major systemic vasculature in micropigs.

PMID- 21897093
TI  - Effects of hydrocortisone and aminophylline on the aggregation of equine
      platelets in vitro.
AB  - The purpose of this study was to evaluate in vitro the effects of hydrocortisone
      and aminophylline on adenosine diphosphate (ADP)-induced platelet aggregation in
      horses. Blood samples from 30 healthy Thoroughbred horses were collected by via
      jugular venipuncture to assess platelet aggregation. Platelet-rich and platelet
      poor plasma were prepared from all samples by centrifugation and divided into
      three different aliquots. In the first aliquot, platelet aggregation was measured
      after platelet activation with 1 uM and 0.5 uM ADP (Group A). In the other two
      aliquots, the effect of a 10 min preincubation with hydrocortisone (Group B) or
      aminophylline (Group C) on ADP-induced aggregation at final ADP concentrations of
      1 uM and 0.5 uM was observed. Platelet aggregation, recorded by an aggregometer,
      was evaluated by measuring the maximum degree of platelet aggregation and the
      initial velocities of platelet aggregation were obtained. Our results
      demonstrated the inhibitory effect of hydrocortisone and the induction effect of
      aminophylline on equine platelet responses in vitro.

PMID- 21897095
TI  - Risk factors associated with bacteriological cure, new infection, and incidence
      of clinical mastitis after dry cow therapy with three different antibiotics.
AB  - Factors affecting bacteriological cure rates (BCR) and new intramammary
      infections (IMI) during the dry period as well as clinical mastitis (CM) during
      early lactation were investigated in 414 German Holstein dairy cows receiving dry
      cow therapy. Cows were treated with either benethamine benzylpenicillin (300,000
      IU), penethamate hydriodide (100,000 IU), and framycetin sulphate (100 mg, n =
      136), or cefquinome (150 mg, n = 135), or benzathine cloxacillin (1,280 mg, n =
      143). Overall BCR, IMI, and CM at parturition were 86.4%, 20.7%, and 4.3%,
      respectively. The three antibiotic treatments differed only in BCR, with
      cloxacillin yielding better results than the others. Udder quarters from cows
      with > 4 lactations had a higher risk of IMI and CM at calving. Chronic changes
      in udder tissues were linked to a lower BCR and were associated with a higher
      risk of CM during early lactation. The risk of CM at calving was higher in udder
      quarters with unspecific or subclinical mastitis before drying off. In
      conclusion, with antibiotic dry cow therapy, age and health status of the udder
      appear to be major determinants of IMI and CM during the dry period and early
      lactation, while BCR was associated with the antibiotic type and udder tissue
      status.

PMID- 21897094
TI  - Determination of staphylococcal exotoxins, SCCmec types, and genetic relatedness
      of Staphylococcus intermedius group isolates from veterinary staff, companion
      animals, and hospital environments in Korea.
AB  - The Staphylococcus (S.) intermedius group (SIG) has been a main research subject
      in recent years. S. pseudintermedius causes pyoderma and otitis in companion
      animals as well as foodborne diseases. To prevent SIG-associated infection and
      disease outbreaks, identification of both staphylococcal exotoxins and
      staphylococcal cassette chromosome mec (SCCmec) types among SIG isolates may be
      helpful. In this study, it was found that a single isolate (one out of 178 SIG
      isolates examined) harbored the canine enterotoxin SEC gene. However, the S.
      intermedius exfoliative toxin gene was found in 166 SIG isolates although the S.
      aureus-derived exfoliative toxin genes, such as eta, etb and etd, were not
      detected. SCCmec typing resulted in classifying one isolate as SCCmec type IV, 41
      isolates as type V (including three S. intermedius isolates), and 10 isolates as
      non-classifiable. Genetic relatedness of all S. pseudintermedius isolates
      recovered from veterinary staff, companion animals, and hospital environments was
      determined by pulsed-field gel electrophoresis. Strains having the same band
      patterns were detected in S. pseudintermedius isolates collected at 13 and 18
      months, suggesting possible colonization and/or expansion of a specific S.
      pseudintermedius strain in a veterinary hospital.

PMID- 21897096
TI  - The critical time of avian leukosis virus subgroup J-mediated immunosuppression
      during early stage infection in specific pathogen-free chickens.
AB  - The critical time of avian leukosis virus subgroup J (ALV-J)-mediated
      immunosuppression was determined by body weight, relative immune organ weight,
      histopathology, and presence of group specific antigen and antibodies in specific
      pathogen-free (SPF) chickens. CD4(+) and CD8(+) cell activity in the spleen,
      total and differential leukocyte counts in blood, and viral RNA levels in spleen
      were measured. Significant growth suppression was observed in the two ALV-J
      infected groups. A strong immune response by infected groups was present in
      spleen at 2-weeks-of-age, but after 4-weeks-of-age, the response decreased
      quickly. The thymus and bursa showed persistent immunosuppression until 4-weeks
      of-age. Proliferation of fibroblasts and dendritic cells were observed in immune
      organs at 4- and 5-weeks-of-age. However, the granulocyte cell number was
      markedly lower in the infected groups than in the control group. In group 1 (day
      1 infection) CD4(+) cells increased during the second week but significantly
      decreased during the fourth week, while group 2 (day 7 infection) showed the
      opposite effect. Viral RNA increased significantly by the fourth week. These data
      identify 3~4 weeks post-infection as the key time at which the ALV-J virus exerts
      its immunosuppressive effects on the host.

PMID- 21897097
TI  - Relationship among blood indicators of lipomobilization and hepatic function
      during early lactation in high-yielding dairy cows.
AB  - Blood indicators are used as a tool to diagnose metabolic disorders. The present
      work was conducted to study the relationships among blood indicators of
      lipomobilization and hepatic function in high-yielding dairy cows. Two groups of
      Holstein cows were studied: 27 early lactation cows and 14 mid lactation cows
      from four different herds with similar husbandry characteristics in Galicia,
      Spain. Blood samples were obtained to measure beta-hydroxybutyrate (BHB), non
      esterified fatty acids (NEFA), triglycerides (TG), and the activity of aspartate
      transaminase (AST) and gamma-glutamyl transferase. Cows in early lactation had
      higher levels of BHB and NEFA than mid lactation cows. High lipomobilization
      (NEFA > 400 umol/L) was detected in 67% and 7% of early lactation and mid
      lactation cows, respectively, while subclinical ketosis (BHB > 1.2 mmol/L) was
      detected in 41% and 28% of the early lactation and lactation cows, respectively.
      TG concentrations were low in all cows suffering subclinical ketosis and in 61%
      of the cows with high lipomobilization. During early lactation, 30% of cows
      suffered hepatic lipidosis as detected by levels of AST. Compromised hepatic
      function was observed in early lactation cows as shown by lower concentrations of
      glucose, total protein, and urea.

PMID- 21897098
TI  - Evaluation of glycoproteins purified from adult and larval camel ticks (Hyalomma
      dromedarii) as a candidate vaccine.
AB  - In order to identify antigens that can help prevent camel tick infestations,
      three major glycoproteins (GLPs) about 97, 66 and 40 kDa in size were purified
      from adult and larval Egyptian ticks, Hyalomma (H.) dromedarii, using a single
      step purification method with Con-A sepharose. The purified GLPs were evaluated
      as vaccines against camel tick infestation in rabbits. The rabbits received three
      intramuscular inoculations of GLPs (20 ug/animal) on days 0, 14, and 28. In the
      immunoblot analysis, Sera from the immunized rabbits recognized the native GLPs
      and other proteins from larval and adult H. dromedarii ticks along with those
      from other tick species such as Rhipicephalus sanguineus but not Ornithodoros
      moubata. The effects of immunity induced by these GLPs were determined by
      exposing rabbits to adult H. dromedarii ticks. These results demonstrated that
      GLP immunization led to a slightly decreased reproductive index and significantly
      reduced rates of egg hatchability. These results demonstrated that immunization
      with the purified GLPs can provide protection against infestation by H.
      dromedarii and some other tick species. Further studies are needed to confirm the
      effectiveness of immunization with GLPs against other tick species.

PMID- 21897099
TI  - Influence of nitric oxide on in vitro growth, survival, steroidogenesis, and
      apoptosis of follicle stimulating hormone stimulated buffalo (Bubalus bubalis)
      preantral follicles.
AB  - Effect of sodium nitroprusside (SNP), a nitric oxide (NO) donor, on in vitro
      survival, growth, steroidogenesis, and apoptosis of buffalo preantral follicles
      (PFs) was investigated. PFs (200~250 um) were isolated by micro-dissection and
      cultured in 0 (control), 10(-3), 10(-5), 10(-7), and 10(-9) M SNP. To examine the
      reversible effect of SNP, PFs were cultured with 10(-5) M SNP + 1 mM N(omega)
      nitro-L-arginine methyl ester (L-NAME) or 1.0 ug hemoglobin (Hb). The results
      showed that greater concentrations of SNP (10(-3), 10(-5), 10(-7) M) inhibited (p
      < 0.05) FSH-induced survival, growth, antrum formation, estradiol production, and
      oocyte apoptosis in a dose-dependent manner. However, a lower dose of SNP (10(-9)
      M) significantly stimulated (p < 0.05) the survival, growth, antrum formation,
      follicular oocyte maturation, and stimulated progesterone secretion compared to
      the control. A combination of SNP + L-NAME promoted the inhibitor effect of SNP
      while a SNP + Hb combination reversed this effect. Nitrate and nitrite
      concentrations in the culture medium increased (p < 0.05) in a dose-dependent
      manner according to SNP concentration in the culture medium. At higher
      concentrations, SNP had a cytotoxic effect leading to follicular oocyte apoptosis
      whereas lower concentrations have stimulatory effects. In conclusion, NO exerts a
      dual effect on its development of buffalo PFs depending on the concentration in
      the culture medium.

PMID- 21897100
TI  - Transmission electron microscopy for characterization of acrosomal damage after
      Percoll gradient centrifugation of cryopreserved bovine spermatozoa.
AB  - The objective of this study was to characterize acrosomal ultrastructure
      following discontinuous Percoll gradient centrifugation of cryopreserved bovine
      sperm. Semen was collected from six bulls of different breeds and three
      ejaculates per bull were evaluated. Frozen semen samples were thawed and the
      acrosomal region of sperm cells was evaluated by transmission electron microscopy
      (TEM) before (n = 18) and after (n = 18) Percoll centrifugation. The evaluation
      of 20 sperm heads from each of the 36 samples analyzed ensured that a large
      number of cells were investigated. The data were subjected to analysis of
      variance at a level of significance of 5%. Percoll centrifugation reduced the
      percentage of sperm exhibiting normal acrosomes (from 61.77 to 30.24%), reduced
      the percentage of sperm presenting atypical acrosome reactions (from 28.38 to
      4.84%) and increased the percentage of sperm exhibiting damage in the acrosome
      (from 6.14 to 64.26%). The percentage of sperm with typical acrosome reactions
      was not significantly different before (3.70%) and after (0.67%) centrifugation.
      TEM distinguished four different types of acrosomal status and enabled
      ultrastructural characterization of acrosomal injuries. The percentage of sperm
      exhibiting normal acrosomes decreased and damage in the acrosome was the most
      frequent acrosomal injury with the Percoll gradient centrifugation protocol
      utilized.

PMID- 21897101
TI  - Biomarkers for identifying the early phases of osteoarthritis secondary to medial
      patellar luxation in dogs.
AB  - The levels of tartrate resistant acid phosphatase (TRAP), matrix
      metalloproteinase-2 (MMP-2), and tissue inhibitor of matrix metalloproteinase-2
      (TIMP-2) in synovial fluid (SF) and serum in cases of canine osteoarthritis (OA)
      were measured. OA was induced by a surgically-created medial patellar luxation in
      the left stifle of 24 dogs. SF and blood samples were collected at 1.5- and 3
      month intervals, respectively. Every 3 months, one dog was euthanatized to
      collect tissue samples from both stifles. TRAP levels in SF and serum were
      measured using a spectrophotometer, and TRAP-positive cells in joint tissues were
      identified by enzyme histochemistry. MMP-2 and TIMP-2 in SF and serum were
      detected by Western blotting and ELISA, respectively. TRAP in SF from the stifles
      and serum was significantly increased (p < 0.05) after 3 months. TIMP-2 in SF and
      serum was significantly decreased (p < 0.05), whereas MMP-2 in SF was
      significantly increased (p < 0.05) during the progression of OA. Histochemistry
      revealed an increased number of TRAP-positive cells in tissues from OA-affected
      joints. Assays measuring TRAP, MMP-2, and TIMP-2 in SF and serum, and methods
      that detect increased numbers of TRAP-positive cells in the joint tissues can
      play an important role in identifying the early phases of degenerative changes in
      canine joint components.

PMID- 21897102
TI  - Sedative and analgesic effects of intravenous xylazine and tramadol on horses.
AB  - This study was performed to evaluate the sedative and analgesic effects of
      xylazine (X) and tramadol (T) intravenously (IV) administered to horses. Six
      thoroughbred saddle horses each received X (1.0 mg/kg), T (2.0 mg/kg), and a
      combination of XT (1.0 and 2.0 mg/kg, respectively) IV. Heart rate (HR),
      respiratory rate (RR), rectal temperature (RT), indirect arterial pressure (IAP),
      capillary refill time (CRT), sedation, and analgesia (using electrical
      stimulation and pinprick) were measured before and after drug administration. HR
      and RR significantly decreased from basal values with X and XT treatments, and
      significantly increased with T treatment (p < 0.05). RT and IAP also
      significantly increased with T treatment (p < 0.05). CRT did not change
      significantly with any treatments. The onset of sedation and analgesia were
      approximately 5 min after both X and XT treatments; however, the XT combination
      produced a longer duration of sedation and analgesia than X alone. Two horses in
      the XT treatment group displayed excited transient behavior within 5 min of drug
      administration. The results suggest that the XT combination is useful for
      sedation and analgesia in horses. However, careful monitoring for excited
      behavior shortly after administration is recommended.

PMID- 21897103
TI  - Common allergens of atopic dermatitis in dogs: comparative findings based on
      intradermal tests.
AB  - Intradermal tests were performed on 58 dogs diagnosed with atopic dermatitis from
      2004~2008 at the Veterinary Medical Teaching Hospital of Konkuk University,
      Korea. To compare the allergen distribution observed in the present investigation
      to the results from other studies conducted in Korea and elsewhere, the allergens
      were grouped according to their kinds. There was no significant difference in
      gender distribution among the dogs. The most common breeds among the 58 dogs were
      Maltese (n = 11) and Shih-tzu (n = 11). The average age was 4.8 years. The most
      frequently produced a positive reaction on the intradermal tests was mold (67.3%)
      followed by house dust (54.5%) and house dust mites (49.1%). The present study
      found a low distribution of dogs allergic to various outdoor allergens compared
      to studies performed in other countries; this may reflect differences in living
      conditions for dogs living in Korea.

PMID- 21897104
TI  - Differential brain angiotensin-II type I receptor expression in hypertensive
      rats.
AB  - Blood-borne angiotensin-II (Ang-II) has profound effects in the brain. We tested
      the hypothesis that Ang-II-dependent hypertension involves differential Ang-II
      type I (AT(1)) receptors expression in the subfornical organ (SFO) and the
      rostral ventrolateral medulla (RVLM). Male Wistar rats were implanted with 14-day
      osmotic minipump filled with Ang-II (150 ng/kg/min) or saline. AT(1) receptor
      mRNA levels were detected in the SFO and RVLM by reverse transcription-polymerase
      chain reaction (RT-PCR). Ang-II caused hypertension (134 +/- 10 mmHg vs. 98 +/- 9
      mmHg, n = 9, p < 0.05). RT-PCR revealed that Ang-II infusion induced increased
      AT(1) receptor mRNA levels in RVLM and decreased in SFO. Our data suggest that
      Ang-II-induced hypertension involves differential expression of brain AT(1)
      receptors.

PMID- 21897105
TI  - Development of a novel diagnostic test for detection of bovine viral diarrhea
      persistently infected animals using hair.
AB  - The purpose of this study was to determine whether manually plucked hairs might
      serve as an alternative sample for a quantitative real time polymerase chain
      reaction (qRT-PCR) testing. Twenty three, 1~3 week old, non-bovine viral diarrhea
      virus (BVDV) vaccinated calves, found to be positive for BVDV by
      immunohistochemical staining, were selected and hairs were manually plucked from
      the ear. qRT-PCR was performed on samples consisting of more than 30 hairs
      (30~100) and whole blood. All 23 animals were positive for the virus by qRT-PCR
      performed on the whole blood and when samples of more than 30 hairs were assayed.
      Additionally, qRT-PCR was performed on groups of 10 and 20 hairs harvested from 7
      out of 23 immunohistochemical staining-positive calves. When groups of 20 and 10
      hairs were tested, 6 and 4 animals, respectively, were positive for the virus.

PMID- 21897106
TI  - Pro- and anti-inflammatory cytokine expression and histopathological
      characteristics in canine brain with traumatic brain injury.
AB  - We analyzed the expression level and cellular localization of pro- and anti
      inflammatory cytokines and histopathologically characterized canine traumatic
      brain injury (TBI). Canine TBI brains revealed subarachnoid and cerebral cortical
      hemorrhage, neutrophilic infiltration, neuronal necrosis, astrocytosis, and
      vasogenic edema. Immunohistochemical evaluations suggested that both pro
      inflammatory cytokines [interleukin (IL)-1beta, IL-6, and tumor necrosis factor
      alpha] and anti-inflammatory cytokines [IL-10 and transforming growth factor-beta
      (TGF-beta)] were highly expressed in neurons and neutrophils. In particular, the
      highest magnitude of expression was identified for IL-1beta and TGF-beta. This
      data helps describe the pathologic characteristics of canine TBI, and may help in
      the design of potential therapeutic approaches to control secondary damage by
      inflammatory cytokines.

PMID- 21897108
TI  - Insulin autoimmune syndrome: a case associated with HLA-DRB1 polymorphism.

PMID- 21897107
TI  - Clinical characteristics and incidence of first fracture in a consecutive sample
      of post-menopausal women attending osteoporosis centers: The PROTEO-1 study.
AB  - BACKGROUND: Osteoporosis is a highly prevalent disease and fractures are a major
      cause of disability and morbidity. AIM: The purpose of this study was to
      characterize post-menopausal women attending osteoporosis centers in Italy, to
      evaluate physician management, and to determine the incidence of first
      osteoporotic fracture. SUBJECTS AND METHODS: PROTEO-1 was an observational
      longitudinal study with a 12-month follow-up. Data were collected from women
      attending osteoporosis centers. Women without prevalent fracture were eligible to
      enter the 1-yr follow-up phase: the clinical approach to patients according to
      their fracture risk profile and the incidence of fracture were recorded. RESULTS:
      4269 patients were enrolled in 80 centers in the cross-sectional phase; 34.2% had
      an osteoporotic fracture at baseline. Patients with prevalent fractures were
      older and more likely to be treated compared with non-fractured patients. The
      incidence of vertebral or hip fracture after 1 yr was 3.84%, regardless of the
      calculated risk factor profile, and was significantly higher in patients with
      back pain at baseline (4.2%) compared with those without back pain (2.2%;
      p=0.023). Generally, physicians prescribed more blood exams and drugs to patients
      at higher risk of fracture. Among fractured patients only 24% were properly
      treated; the rate of non-responders to treatment was about 4%. CONCLUSIONS: In a
      large, unselected sample of post-menopausal women attending osteoporosis centers,
      those without previous fracture were at substantial risk of future fracture,
      regardless of their theoretical low 10-yr fracture risk. The presence of back
      pain in women without previous fracture warrants close attention.

PMID- 21897109
TI  - Paternity in Klinefelter syndrome - another case report.

PMID- 21897110
TI  - Endocrinology and Art. Madonna Enthroned with Child - Cenni di Pepo called
      Cimabue (Florence 1240-Pisa 1302).

PMID- 21897111
TI  - Cell proliferation parameters and apoptosis indices in pituitary macroadenomas.
AB  - BACKGROUND: Pituitary adenomas are usually well-differentiated tumors but may
      show locally aggressive behavior. AIM: To investigate the relationship between
      proliferation and apoptosis parameters and tumor recurrence in a series of 20
      radically resected pituitary macroadenomas (11 functioning, 9 non-functioning).
      MATERIALS AND METHODS: Proliferative activity and DNA ploidy were analyzed by
      flow cytometry (FCM) on fresh surgical specimens. Immunohistochemistry for Ki
      67/MIB-1 and for the anti-apoptotic protein Bcl-2 was performed on paraffin
      embedded specimens from the same tumors. Tumor regrowth was evaluated by magnetic
      resonance imaging (MRI). RESULTS: Six adenomas recurred after surgery, regardless
      of hormonal hypersecretion. Pre-surgical tumor size was significantly higher in
      recurrent than in non-recurrent adenomas (p=0.003). Pre-surgical MRI demonstrated
      cavernous sinus (CS) invasiveness in all recurrent tumors, while none of the non
      invasive adenomas recurred (p=0.042, by Fisher's exact test). The DNA content was
      aneuploid in 5/20 adenomas, one of which recurred. Cell percentages in the S
      (%SPF) and G2+M (%G2-M) phases and proliferative index (PI) (PI=%SPF+%G2-M) were
      significantly higher in aneuploid than in diploid adenomas (p<0.05), but no
      significant differences concerning all FCM parameters were observed between
      recurrent and non-recurrent adenomas. Similarly, MIB-1 did not show a significant
      difference of expression between recurrent and non-recurrent adenomas (p=0.33).
      Bcl-2 immunoreactivity was detected in 12/15 pituitary adenomas, involving 63+/
      35% of tumor cells, regardless of tumor recurrence. CONCLUSIONS: In this group of
      radically resected pituitary macroadenomas, neuroradiological finding of CS
      invasiveness--but not FCM parameters nor MIB-1 and Bcl-2 expression--is useful
      for predicting tumor recurrence.

PMID- 21897112
TI  - Association of -55CT polymorphism of UCP3 gene with fat distribution,
      cardiovascular risk factors and adipocytokines in patients with Type 2 diabetes
      mellitus.
AB  - BACKGROUND AND AIMS: Some studies have pointed to a role of uncoupling protein 3
      (UCP3) in the regulation of fat distribution. The aim of our study was to
      investigate the influence of -55CT polymorphism of UCP3 gene on fat mass and
      adipocytokines in naive patients with Type 2 diabetes mellitus. DESIGN: A
      population of 57 patients with Type 2 diabetes mellitus and obesity was analyzed
      in a cross-sectional study. Genotype of UCP3 gene -55CT was studied. RESULTS:
      Forty-six patients (80.7%) had the 55CC genotype and 11 patients (19.3%) the 55CT
      genotype. Fat mass (39.1+/-15.4 vs 53.3+/-16.8 kg; p<0.05), weight (92.6+/-17.7
      vs 106.3+/-17.3 kg; p<0.05), body mass index (36.2+/-6.5 vs 42.8+/-5.2 kg/m2;
      p<0.05), waist circumference (112.8+/-13.6 vs 127.9+/-12.3 cm; p<0.05), waist-to
      hip ratio (0.96+/-0.1 vs 1.1+/-0.2; p<0.05), C reactive protein (6.1+/-5.1 vs
      12.4+/-6.1 mg/dl; p<0.05) and leptin (92.8+/-86 vs 114+/-89 ng/ml; p<0.05) were
      higher in patients with mutant genotype than in those with wild genotype.
      CONCLUSION: C reactive protein and fat mass were higher in the mutant group of 
      55 CT UCP3 gene diabetic patients than in wild type patients.

PMID- 21897113
TI  - Metabolic changes after a hypocaloric, low-glycemic-index diet in obese children.
AB  - BACKGROUND: A low glycemic index (LGI) diet has been proposed as a treatment for
      obesity in adults; few studies have evaluated LGI diets in obese children. AIM:
      The purpose of the study was to compare the effects of two diets, with similar
      energy intakes, but different glycemic indexes in a pediatric outpatient setting.
      SUBJECTS AND METHODS: A parallel- group, randomized controlled trial was
      conducted, and 22 obese outpatient children with a body mass index (BMI) Z-score
      >2 (11 females and 11 males, BMI 28.9+/-2.9 kg/m2) were included in the study.
      Patients were randomly allocated to a hypocaloric LGI (GI:60), or to a
      hypocaloric high glycemic index (HGI) diet (GI:90). The LGI and HGI diets were
      almost equivalent for macronutrient composition. Anthropometric and biochemical
      parameters were measured at baseline and after 6 months. RESULTS: In both groups
      there were significant decreases in BMI, BMI Z-score, blood pressure, and high
      sensitivity C-reactive protein. Only LGI diets produced a significant decrease in
      waist circumference and homeostasis model assessment. Analysis of variance
      demonstrated that the BMI Z-score decrease from baseline values was significantly
      greater after the LGI diet than after the HGI diet [-0.20 (95% confidence
      interval (CI) -0.29 to -0.10) vs -0.34 (95%CI -0.43 to -0.24)], mean difference
      between groups -0.14 (95%CI -0.27 to -0.01), p<0.05). Changes in triglyceride
      concentrations were significantly lower in LGI as compared to HGI diet (p<0.05).
      CONCLUSIONS: This study demonstrates that a hypocaloric LGI diet has beneficial
      metabolic effects in comparison to a hypocaloric HGI diet in obese children.

PMID- 21897114
TI  - Basal STAT3 activities are negatively correlated with tumor size in papillary
      thyroid carcinomas.
AB  - BACKGROUNDS: Signal transducer and activators of transcription-3 (STAT3) plays a
      critical role in promoting survival and cell growth as well as facilitating
      angiogenesis and metastasis in several cancers. AIM: This investigation focused
      on evaluation of STAT3 activities in human papillary thyroid cancers (PTC).
      METHODS: STAT3 activities of nuclear extracts of tumor tissue were measured from
      35 PTC patients using enzyme- linked immunosorbent assay-based kits. RESULTS:
      STAT3 activities of PTC tissues were significantly lower than those of
      surrounding normal thyroid tissues [0.36 (interquartile range 0.24-0.72) vs 0.50
      (0.29-1.11) arbitrary units, p<0.01]. We further analyzed the association between
      STAT3 activity and clinicopathologic factors in PTC tissue. Tumors with size >=2
      cm displayed significantly lower STAT3 activities than those <2 cm [0.25 (0.21
      0.37) vs 0.53 (0.37-0.61) arbitrary units, p<0.01]. Notably, tumor size was
      inversely correlated with STAT3 activities in T1799A BRAF mutation-positive cases
      (Rs=-0.58, p<0.05), but not mutation-negative cases. CONCLUSIONS: STAT3
      activities of PTC measured via DNA binding are suppressed in contrast to other
      human cancers. Tumor size larger than 2 cm is the only clinicopathologic
      parameter associated with low STAT3 activity. Moreover, tumor size appears
      inversely correlated with STAT3 activity, specifically in T1799A BRAF mutation
      positive cases.

PMID- 21897115
TI  - Validation of immunohistochemistry for somatostatin receptor subtype 2A in human
      somatotropinomas: comparison between quantitative real time RT-PCR and
      immunohistochemistry.
AB  - Somatostatin receptors subtype 2 (SSTR2) expression in somatotropinomas is
      recognized as a predictor of response to the currently available somatostatin
      analogs and may be analyzed, mainly, by quantitative RT-PCR or
      immunohistochemistry (IHC). The former has the advantages of a higher sensitivity
      and of being quantitative, while the latter, although semi-quantitative,
      evaluates protein expression and is routinely used in the evaluation of pituitary
      adenomas. We aimed to evaluate the SSTR2A protein expression in somatotropinomas
      and to compare it to our previous data regarding mRNA expression, assessed by
      quantitative real time RTPCR. Thirteen somatotropinomas were analyzed by IHC and
      the tumors were scored according to percent of immunostained cells: 0 (<25%), 1
      (25-50%) and 2 (>50%). SSTR2A immunostaining was present in all but one
      somatotropinoma, 4 (31%) tumors were classified as score 0, 4 (31%) as score 1,
      and 5 (38%) as score 2. Median SSTR2 mRNA content was significantly different
      among the three IHC scores (p=0.036) and was lower in the score 0 than in the
      score 2 (p=0.016). The finding that there is a positive correlation between RT
      PCR and IHC indicates that IHC can be applied in order to assess the SSTR2A
      content in somatotropinomas.

PMID- 21897117
TI  - Characterization of novel antisense HIF-1alpha transcripts in human cancers.
AB  - Whole transcriptome analyses have revealed new classes of long ncRNA (lncRNA),
      the functions of which are however largely unknown. Recently, we showed that the
      antitumor DNA topoisomerase I (Top1) inhibitor camptothecin (CPT) increases the
      cellular levels of two antisense lncRNAs at the 5' (5'aHIF-1alpha) and 3' (3'aHIF
      1alpha) ends of the human HIF-1alpha gene. To gain insights into their functions,
      we have here determined structural and functional aspects of the two antisense
      RNAs in human cancer cell lines and kidney tumor specimen. We found that the
      antisense transcripts are activated in response to partially different kinds of
      stress, and that the 5'aHIF-1alpha has a 5'Cap and a poly(A+) tail, while the
      3'aHIF-1alpha is known to lack both modifications. Cell fractionation experiments
      showed that 5' and 3' antisense RNAs are nuclear transcripts. Further analyses by
      RNA-FISH showed that the 5'aHIF-1alpha accumulates at the perinuclear cellular
      compartment and co-localizes with the nuclear pore complex Nup62 protein,
      suggesting a role in nuclear membrane trafficking. Finally, we provide evidence
      that the studied antisense lncRNAs are expressed in human kidney cancer tissues,
      highlighting their possible roles in cancer development. Altogether, our findings
      may suggest a novel function of 5'aHIF-1alpha in membrane transport that may
      regulate the cancer-relevant HIF-1alpha pathway.

PMID- 21897116
TI  - Molecular genetics of retinal degeneration: A Drosophila perspective.
AB  - Inherited retinal degeneration in Drosophila has been explored for insights into
      similar processes in humans. Based on the mechanisms, I divide these mutations in
      Drosophila into three classes. The first consists of genes that control the
      specialization of photoreceptor cells including the morphogenesis of visual
      organelles  (rhabdomeres) that house the visual signaling proteins. The second
      class contains genes that regulate the activity or level of the major rhodopsin,
      Rh1, which is the light sensor and also provides a structural role for the
      maintenance of rhabdomeres. Some mutations in Rh1 (NinaE) are dominant due to
      constitutive activity or folding defects, like autosomal dominant retinitis
      pigmentosa (ADRP) in humans. The third class consists of genes that control the
      Ca ( 2+) influx directly or indirectly by promoting the turnover of the second
      messenger and regeneration of PIP 2, or mediate the Ca ( 2+) -dependent
      regulation of the visual response. These gene products are critical for the
      increase in cytosolic Ca ( 2+ ) following light stimulation to initiate negative
      regulatory events. Here I will focus on the signaling mechanisms underlying the
      degeneration in norpA, and in ADRP-type NinaE mutants that produce misfolded Rh1.
      Accumulation of misfolded Rh1 in the ER triggers the unfolded protein response
      (UPR), while endosomal accumulation of activated Rh1 may initiate autophagy in
      norpA. Both autophagy and the UPR are beneficial for relieving defective
      endosomal trafficking and the ER stress, respectively. However, when
      photoreceptors fail to cope with the persistence of these stresses, a cell death
      program is activated leading to retinal degeneration.

PMID- 21897118
TI  - Erlotinib antagonizes constitutive activation of SRC family kinases and mTOR in
      acute myeloid leukemia.
AB  - Tyrosine kinases such as SRC family kinases (SFKs) as well as the mammalian
      target of rapamycin (mTOR) serine/threonine kinase are often constitutively
      activated in acute myeloid leukemia (AML) and hence constitute potential
      therapeutic targets. Here we demonstrate that the epidermal growth factor
      receptor (EGFR) inhibitor erlotinib, which has previously been shown to mediate
      antiproliferative/cytotoxic off-target effects in myelodysplastic syndrome (MDS)
      and AML blasts, reduces SFK overactivation. Erlotinib induced an arrest in the G
      1 phase of the cell cycle that, in cells with constitutive SFK activation, could
      be recapitulated by chemical inhibition of SFKs with 3-(4-chlorophenyl)1-(1,1
      dimethylethyl)-1H-pyrazolo[3,4-alpha]pyrimidin-4-amine (PP2). Moreover, erlotinib
      inhibited the phosphorylation of mTOR targets like p70 (SK6) , stimulated the
      maturation of the autophagic marker LC3 and promoted the formation of
      autophagosomes. Notably, PP2 and the mTOR inhibitor rapamycin had a similar cell
      cycle-arresting activity to erlotinib, but neither of these compounds alone
      induced significant levels of cell death. Altogether, these results suggest that
      the therapeutic off-target effect of erlotinib may be linked to, yet cannot be
      entirely explained by, the inhibition of oncogenic signaling via SFKs and mTOR.
      Thus, combination therapies with erlotinib and rapamycin might be beneficial for
      MDS and AML patients.

PMID- 21897119
TI  - Overexpression of VEGF189 in breast cancer cells induces apoptosis via NRP1 under
      stress conditions.
AB  - The existence of multiple VEGF-A isoforms raised the possibility that they may
      have distinct functions in tumor growth. We have previously published that
      VEGF189 and VEGF165 contribute to breast cancer progression and angiogenesis, but
      VEGF165 induced the most rapid tumor uptake. Since VEGF165 has been described as
      a survival factor for breast tumor cells, we questioned here the effects of
      VEGF189 on the survival/apoptosis of MDA-MB-231 cells. We used clones which
      overexpress VEGF189 (V189) or VEGF165 (V165) isoforms and compared them to a
      control one (cV). Overexpression of VEGF189 resulted in increased cell apoptosis,
      as determined by Annexin-V apoptosis assay, under serum starvation and
      doxorubicin treatment, while VEGF 165 was confirmed to be a survival factor.
      Since MDA-MB-231 highly express NRP1 (a co-receptor for VEGF-A), we used short
      hairpin RNA (shRNA) to knockdown NRP1 expression. V189shNRP1 clones were
      characterized by reduced apoptosis and higher necrosis, as compared to V189shCtl,
      under stress conditions. Unexpectedly, NRP1 knock-down had no effect on the
      survival or apoptosis of V165 cells. VEGF189 showed greater affinity towards NRP1
      than VEGF165 using a BIAcore binding assay. Finally, since endogenously produced
      urokinase-type plasminogen (uPA) has been found to prevent apoptosis in breast
      cancers, we analyzed the level of uPA activity in our clones. An inhibition of
      uPA activity was observed in V189shNRP1 clones. Altogether, these results suggest
      a major role of NRP1 in apoptosis induced by VEGF189 in stress conditions and
      confirm VEGF165 as a survival factor.

PMID- 21897120
TI  - Lipid droplet formation protects against gluco/lipotoxicity in Candida
      parapsilosis: an essential role of fatty acid desaturase Ole1.
AB  - Elevated levels of glucose and lipids can result in cellular dysfunction in
      eukaryotic cells ranging from Saccharomyces cerevisiae yeasts to human cells.
      Moreover, glucotoxicity and lipotoxicity can cause cell death, although the
      mechanism(s) for lethality is unclear. In the present study, we utilized Candida
      parapsilosis fatty acid desaturase (OLE1) and fatty acid synthase (FAS2) gene
      deletion mutants and wild-type (WT) yeast cells to unravel the relationship to
      glucose and lipid induced cell death in eukaryotic cells. Incubation of WT yeast
      cells with glucose led to the rapid accumulation of lipid droplets, whereas lipid
      droplet formation was severely impaired in yeast cells with deletion of OLE1
      (ole1Delta/Delta) or FAS2 (fas2Delta/Delta). Interestingly, ole1Delta/Delta yeast
      cells died within hours in a 1% glucose medium without fatty acid
      supplementation, whereas the WT or fas2Delta/Delta yeast cells did not. In
      glucose medium, ole1Delta/Delta yeast cells accumulated saturated fatty acids,
      while fas2Delta/Delta did not. Addition of saturated fatty acids (e.g., palmitic
      acid) enhanced ole1Delta/Delta yeast cell death, whereas the addition of
      unsaturated fatty acids (e.g., oleic or palmitoleic acid) rescued cell death.
      Furthermore, palmitic acid and glucose medium induced apopotic cell death in
      ole1Delta/Delta yeast cells, which was dependent on mitochondrial function. Thus,
      our results show that glucotoxicity is directly linked to lipotoxicity, which we
      demonstrate is mediated by mitochondrial function.

PMID- 21897121
TI  - Isolation and in silico analysis of promoter of a high salinity stress-regulated
      pea DNA helicase 45.
AB  - Helicases are motor proteins that can transiently catalyze the unwinding of
      energetically stable duplex DNA or RNA molecules by using ATP hydrolysis as the
      source of energy. Many helicases share a core region of highly conserved sequence
      motifs, and belong to the rapidly growing DEAD-box protein family. Pea DNA
      helicase 45 (PDH45), that exhibits striking homology with eukaryotic translation
      initiation factor 4A (eIF4A), contains ATP-dependent DNA and RNA helicase, DNA
      dependent ATPase, and ATP-binding activities. The transcript of the PDH45 gene
      was reported to be upregulated in pea plant in response to high salinity, cold
      stress, abscisic acid (ABA), dehydration and early wounding. The first direct
      evidence that overexpression of PDH45 confers salinity stress tolerance without
      yield loss has also been reported. A promoter analysis of PDH45 gene has not been
      studied. The cis-regulatory elements present on promoter region of the gene act
      as binding sites for RNA polymerase and transcription factors and control the
      regulation of gene expression. Here we report the promoter of the PDH45 gene that
      contains stress-responsive cis-regulatory elements which may be responsible for
      regulating the expression of PDH45 under abiotic stress conditions.

PMID- 21897122
TI  - Carbon and nitrogen metabolism regulated by the ubiquitin-proteasome system.
AB  - The ubiquitin-proteasome system (UPS) is a unique protein degradation mechanism
      conserved in the eukaryotic cell. In addition to the control of protein quality,
      UPS regulates diverse cellular signal transduction via the fine-tuning of target
      protein degradation. Protein ubiquitylation and subsequent degradation by the 26S
      proteasome are involved in almost all aspects of plant growth and development and
      response to biotic and abiotic stresses. Recent studies reveal that the UPS plays
      an essential role in adaptation to carbon and nitrogen availability in plants.
      Here we highlight ubiquitin ligase ATL31 and the homologue ATL6 target 14-3-3
      proteins for ubiquitylation to be degraded, which control signaling for carbon
      and nitrogen metabolisms and C/N balance response. We also give an overview of
      the UPS function involved in carbon and nitrogen metabolisms.

PMID- 21897123
TI  - Revealing plant defense signaling: getting more sophisticated with
      phosphoproteomics.
AB  - The regulation mechanisms of any plant-pathogen interaction are complex and
      dynamic.  A proteomic approach is necessary in understanding regulatory networks
      because it identifies new proteins in relation to their function and ultimately
      aims to clarify how their expression, accumulation and modification is
      controlled. One of the major control mechanisms for protein activity in plant
      pathogen interactions is protein phosphorylation, and an understanding of the
      significance of protein phosphorylation in plant-pathogen interaction can be
      overwhelming. Due to the high number of protein kinases and phosphatases in any
      single plant genome and specific limitations of any technologies, it is extremely
      challenging for us to fully delineate the phosphorylation machinery. Current
      proteomic approaches and technology advances have demonstrated their great
      potential in identifying new components. Recent studies in well-developed plant
      pathogen systems have revealed novel phosphorylation pathways, and some of them
      are off the core phosphorylation cascades. Additional phosphoproteomic studies
      are needed to increase our comprehension of the different mechanisms and their
      fine tuning involved in the host resistance response to pathogen attacks.

PMID- 21897125
TI  - Cataloging proteins putatively secreted during the biotrophy-necrotrophy
      transition of the anthracnose pathogen Colletotrichum truncatum.
AB  - Hemibiotrophic phytopathogenic fungi cause devastating diseases in agronomically
      important crops. These fungal pathogens exploit a stealth bi-phasic infection
      strategy to colonize host plants. Their morphological and nutritional transition
      from biotrophy (characterized by voluminous intracellular primary hyphae) to
      necrotrophy (characterized by thin secondary hyphae) known as the biotrophy
      necrotrophy switch (hemibiotrophy) is critical in symptom and disease
      development. To establish successful hemibiotrophic parasitism, pathogens likely
      secrete suites of proteins at the switch that constitute the biotrophy
      necrotrophy switch secretome. To catalogue such proteins, a directional cDNA
      library was constructed from mRNA isolated from infected Lens culinaris leaflet
      tissues displaying the switch of Colletotrichum truncatum, and 5000 expressed
      sequence tags (ESTs) were generated. Four potential groups (hydrolytic enzymes,
      cell envelope-associated proteins [CEAPs], candidate effectors and proteins with
      diverse functions) were identified from pathogen-derived ESTs. Expression
      profiling of transcripts encoding CEAPs and candidate effectors in an infection
      time-course revealed that the majority of these transcripts were expressed or
      induced during the necrotrophic phase and repressed during the biotrophic phase
      of in planta colonization, indicating the massive accumulation of proteins at the
      switch. Taken together, our data suggest that the hemibiotrophic mode of fungal
      proliferation entails complex interactions of a pathogen with its host wherein
      the pathogen requires live host cells prior to switching to the necrotrophic
      phase. The microbial proteins employed during pathogenesis are likely to have
      defined roles at specific stages of pathogenesis.

PMID- 21897124
TI  - The role of transcriptional coactivator ADA2b in Arabidopsis abiotic stress
      responses.
AB  - Plant growth and crop production can be greatly affected by common environmental
      stresses such as drought, high salinity and low temperatures. Gene expression is
      affected by several abiotic stresses. Stress-inducible genes are regulated by
      transcription factors and epigenetic mechanisms such as histone modifications. In
      this Mini-Review, we have explored the role of transcriptional adaptor ADA2b in
      Arabidopsis responses to abiotic stress. ADA2b is required for the expression of
      genes involved in abiotic stress either by controlling H3 and H4 acetylation in
      the case of salt stress or affecting nucleosome occupancy in low temperatures
      response.

PMID- 21897126
TI  - For security and stability: SGT1 in plant defense and development.
AB  - SGT1 (suppressor of G-two allele of SKP1) is highly conserved among all
      eukaryotes. In plants, SGT1 interacts with various proteins, including molecular
      chaperones (HSP70 and HSP90) and certain SCF ubiquitin ligases, and hence SGT1
      likely functions in protein folding and stability. Since these protein complexes
      are involved in many aspects of plant biology, plants with a defective SGT1
      display a plethora of phenotypic alterations. In this review we highlight the
      interaction between SGT1 with other protein complexes and summarize the function
      of SGT1 in plant defense responses and development, including the recent
      advancements in the understanding of the role of SGT1 in jasmonic acid (JA)
      biosynthesis and signaling.

PMID- 21897127
TI  - Information theory and the ethylene genetic network.
AB  - The original aim of the Information Theory (IT) was to solve a purely technical
      problem: to increase the performance of communication systems, which are
      constantly affected by interferences that diminish the quality of the transmitted
      information. That is, the theory deals only with the problem of transmitting with
      the maximal precision the symbols constituting a message. In Shannon's theory
      messages are characterized only by their probabilities, regardless of their value
      or meaning. As for its present day status, it is generally acknowledged that
      Information Theory has solid mathematical foundations and has fruitful strong
      links with Physics in both theoretical and experimental areas. However, many
      applications of Information Theory to Biology are limited to using it as a
      technical tool to analyze biopolymers, such as DNA, RNA or protein sequences. The
      main point of discussion about the applicability of IT to explain the information
      flow in biological systems is that in a classic communication channel, the
      symbols that conform the coded message are transmitted one by one in an
      independent form through a noisy communication channel, and noise can alter each
      of the symbols, distorting the message; in contrast, in a genetic communication
      channel the coded messages are not transmitted in the form of symbols but
      signaling cascades transmit them. Consequently, the information flow from the
      emitter to the effector is due to a series of coupled physicochemical processes
      that must ensure the accurate transmission of the message. In this review we
      discussed a novel proposal to overcome this difficulty, which consists of the
      modeling of gene expression with a stochastic approach that allows Shannon
      entropy (H) to be directly used to measure the amount of uncertainty that the
      genetic machinery has in relation to the correct decoding of a message
      transmitted into the nucleus by a signaling pathway. From the value of H we can
      define a function I that measures the amount of information content in the input
      message that the cell's genetic machinery is processing during a given time
      interval. Furthermore, combining Information Theory with the frequency response
      analysis of dynamical systems we can examine the cell's genetic response to input
      signals with varying frequencies, amplitude and form, in order to determine if
      the cell can distinguish between different regimes of information flow from the
      environment. In the particular case of the ethylene signaling pathway, the amount
      of information managed by the root cell of Arabidopsis can be correlated with the
      frequency of the input signal. The ethylene signaling pathway cuts off very low
      and very high frequencies, allowing a window of frequency response in which the
      nucleus reads the incoming message as a varying input. Outside of this window the
      nucleus reads the input message as an approximately non-varying one. This
      frequency response analysis is also useful to estimate the rate of information
      transfer during the transport of each new ERF1 molecule into the nucleus.
      Additionally, application of Information Theory to analysis of the flow of
      information in the ethylene signaling pathway provides a deeper insight in the
      form in which the transition between auxin and ethylene hormonal activity occurs
      during a circadian cycle. An ambitious goal for the future would be to use
      Information Theory as a theoretical foundation for a suitable model of the
      information flow that runs at each level and through all levels of biological
      organization.

PMID- 21897129
TI  - Effect of Cu content on the activity of Cu/ZnSOD1 in the Arabidopsis SUMO E3
      ligase siz1 mutant.
AB  - In a previous study, we found copper (Cu) accumulated to a higher level in the
      aerial parts of soil-grown plants of the SUMO E3 ligase siz1 mutant than in those
      of the wild type. Here, we found that all superoxide dismutase (SOD) isoforms,
      such as FeSOD, MnSOD and different types of Cu/ZnSOD, were more active in the
      siz1 mutant than in the wild type under normal growth conditions. We further
      examined the expression and enzymatic activity of Cu/ZnSOD1 (CSD1) in shoots of
      the siz1 mutant under excess Cu. Shoot CSD1 protein level and activity were
      reduced in siz1 with excess Cu but induced in the wild type. SIZ1-dependent
      SUMOylation may be involved in maintaining CSD1 protein stability or repelling a
      feedback regulation under Cu stress.

PMID- 21897128
TI  - Fungal lectin of Peltigera canina induces chemotropism of compatible Nostoc cells
      by constriction-relaxation pulses of cyanobiont cytoskeleton.
AB  - A glycosylated arginase acting as a fungal lectin from Peltigera canina is able
      to produce recruitment of cyanobiont Nostoc cells and their adhesion to the
      hyphal surface. This implies that the cyanobiont would develop organelles to
      motility towards the chemoattractant. However when visualized by transmission
      electron microscopy, Nostoc cells recently isolated from P. canina thallus do not
      reveal any motile, superficial organelles, although their surface was covered by
      small spindles and serrated layer related to gliding. The use of S-(3,4
      dichlorobenzyl)isothiourea, blebbistatin, phalloidin and latrunculin A provide
      circumstantial evidence that actin microfilaments rather than MreB, the actin
      like protein from prokaryota, and, probably, an ATPase which develops contractile
      function similar to that of myosin II, are involved in cell motility. These
      experimental facts, the absence of superficial elements (fimbriae, pili or
      flagellum) related to cell movement, and the appearance of sunken cells during of
      after movement verified by scanning electron microscopy, support the hypothesis
      that the motility of lichen cyanobionts could be achieved by contraction
      relaxation episodes of the cytoskeleton induced by fungal lectin act as a
      chemoattractant.

PMID- 21897130
TI  - Low temperature-induced necrosis shows phenotypic plasticity in wheat triploid
      hybrids.
AB  - Hybrid necrosis sometimes appears in triploid hybrids between tetraploid wheat
      and Aegilops tauschii Coss. Two types of hybrid necrosis (type II and type III)
      were observed when cultivar Langdon was used as female parent for hybrid
      production. Type II necrosis symptoms occurred only under low temperature
      conditions, whereas bushy and dwarf phenotypes were observed under normal
      temperature conditions. The developmental plasticity might be related to a
      temperature-responsive alteration of meristematic activity at the crown tissue of
      triploid hybrids. Epistatic interaction between the AB and D genomes induced not
      only upregulation of a number of defense-related genes, but also extensive
      changes in plant architecture in the type II necrosis hybrids. Such phenotypic
      plasticity was also observed in other cross combinations between cultivated
      tetraploid wheat and type II necrosis-induced Ae. tauschii accessions. Wild
      tetraploid wheat, Triticum turgidum subspecies dicoccoides, did not induce type
      II necrosis in the triploid hybrids, indicating the possibility of identifying
      the chromosomal location of a causal gene for type II necrosis in the AB genome.

PMID- 21897132
TI  - Comparative effectiveness research for health care administration.

PMID- 21897131
TI  - Plant dehydrins and stress tolerance: versatile proteins for complex mechanisms.
AB  - Dehydrins (DHNs), or group 2 LEA (Late Embryogenesis Abundant) proteins, play a
      fundamental role in plant response and adaptation to abiotic stresses. They
      accumulate typically in maturing seeds or are induced in vegetative tissues
      following salinity, dehydration, cold, and freezing stress. The generally
      accepted classification of dehydrins is based on their structural features, such
      as the presence of conserved sequences, designated as Y, S, and K segments. The K
      segment representing a highly conserved 15 amino acid motif forming amphiphilic
      alpha-helix is especially important since it has been found in all dehydrins.
      Since more than 20 years, they are thought to play an important protective role
      during cellular dehydration but their precise function remains unclear. This
      review outlines the current status of the progress made towards the structural,
      physico-chemical and functional characterization of plant dehydrins and how these
      features could be exploited in improving stress tolerance in plants. 

PMID- 21897135
TI  - Fuchs heterochromic iridocyclitis and the rubella virus.

PMID- 21897136
TI  - Ocular toxoplasmosis: advances in detection and treatment.

PMID- 21897137
TI  - New diagnosis and treatment paradigms in acute retinal necrosis.

PMID- 21897138
TI  - Diagnostic and therapeutic considerations in fungal keratitis.

PMID- 21897139
TI  - Current evidence for topical azithromycin 1% ophthalmic solution in the treatment
      of blepharitis and blepharitis-associated ocular dryness.

PMID- 21897140
TI  - Antiviral chemoprophylaxis for ocular viral infections in hematopoietic stem cell
      and bone marrow transplant patients.

PMID- 21897141
TI  - Prophylaxis against postoperative endophthalmitis in cataract surgery.

PMID- 21897142
TI  - Bacterial conjunctivitis in children: a current review of pathogens and
      treatment.

PMID- 21897143
TI  - Medical treatment for cytomegalovirus retinitis.

PMID- 21897144
TI  - Infectious theories of Posner-Schlossman syndrome.

PMID- 21897145
TI  - An epigenetic approach toward understanding ocular alpha-herpesvirus pathogenesis
      and treatment.

PMID- 21897146
TI  - Ocular toxocariasis: advances in diagnosis and treatment.

PMID- 21897147
TI  - Current diagnostic approaches to infectious anterior uveitis.

PMID- 21897148
TI  - Nonantibiotic therapy in the management of bacterial keratitis.

PMID- 21897149
TI  - Vancomycin resistance in ocular infections.

PMID- 21897150
TI  - Local treatment of Kaposi sarcoma of the conjunctiva.

PMID- 21897153
TI  - Role of sepiapterin on endothelial nitric oxide synthase in acute kidney injury:
      an enigmatic story.

PMID- 21897154
TI  - Disruption of the actin cytoskeleton up-regulates iNOS expression in vascular
      smooth muscle cells: retraction.

PMID- 21897156
TI  - World Federation of Pediatric Intensive Care and Critical Care Societies: Global
      Sepsis Initiative.
AB  - BACKGROUND: According to World Health Organization estimates, sepsis accounts for
      60%-80% of lost lives per year in childhood. Measures appropriate for resource
      scarce and resource-abundant settings alike can reduce sepsis deaths. In this
      regard, the World Federation of Pediatric Intensive Care and Critical Care
      Societies Board of Directors announces the Global Pediatric Sepsis Initiative, a
      quality improvement program designed to improve quality of care for children with
      sepsis. OBJECTIVES: To announce the global sepsis initiative; to justify some of
      the bundles that are included; and to show some preliminary data and encourage
      participation. METHODS: The Global Pediatric Sepsis Initiative is developed as a
      Web-based education, demonstration, and pyramid bundles/checklist tool
      (http://www.pediatricsepsis.org or http://www.wfpiccs.org). Four health resource
      categories are included. Category A involves a nonindustrialized setting with
      mortality rate <5 yrs and >30 of 1,000 children. Category B involves a
      nonindustrialized setting with mortality rate <5 yrs and <30 of 1,000 children.
      Category C involves a developing industrialized nation. In category D, developed
      industrialized nation are determined and separate accompanying administrative and
      clinical parameters bundles or checklist quality improvement recommendations are
      provided, requiring greater resources and tasks as resource allocation increased
      from groups A to D, respectively. RESULTS: In the vanguard phase, data for 361
      children (category A, n = 34; category B, n = 12; category C, n = 84; category D,
      n = 231) were successfully entered, and quality-assurance reports were sent to
      the 23 participating international centers. Analysis of bundles for categories C
      and D showed that reduction in mortality was associated with compliance with the
      resuscitation (odds ratio, 0.369; 95% confidence interval, 0.188-0.724; p <
      .0004) and intensive care unit management (odds ratio, 0.277; 95% confidence
      interval, 0.096-0.80) bundles. CONCLUSIONS: The World Federation of Pediatric
      Intensive Care and Critical Care Societies Global Pediatric Sepsis Initiative is
      online. Success in reducing pediatric mortality and morbidity, evaluated yearly
      as a measure of global child health care quality improvement, requires ongoing
      active recruitment of international participant centers. Please join us at
      http://www.pediatricsepsis.org or http://www.wfpiccs.org.

PMID- 21897157
TI  - Pediatric sepsis: a new challenge for a global quality improvement action.

PMID- 21897158
TI  - Creating or preventing opioid addiction, finding the right dose.

PMID- 21897159
TI  - Transfusion in pediatric sepsis: less may not be more, but it is at least as
      good.

PMID- 21897160
TI  - Transfusion-related immunomodulation: how much of it is due to white cells?

PMID- 21897161
TI  - Pediatric cardiopulmonary bypass and the inflammatory response: years of
      investigation, only incremental progress.

PMID- 21897162
TI  - Are children with genetic disorders at increased risk of postoperative
      complications after cardiac surgery?

PMID- 21897163
TI  - Clinical management of pediatric tracheo-bronchomalacia.

PMID- 21897164
TI  - Intracranial pressure monitoring in children: back to basics.

PMID- 21897165
TI  - Neurological injuries are common contributors to pediatric intensive care unit
      deaths: a wake-up call.

PMID- 21897166
TI  - Glial fibrillary acidic protein: a promising biomarker in pediatric brain injury.

PMID- 21897168
TI  - Neonatal herpes virus infection: duration of extracorporeal support and the dose
      of acyclovir.

PMID- 21897170
TI  - Central extracorporeal membrane oxygenation for refractory pediatric septic
      shock.

PMID- 21897171
TI  - Moving beyond the status quo: excellence in prognostication requires both science
      and art.

PMID- 21897172
TI  - Hemodynamic monitoring by pulse contour analysis in critically ill children with
      congenital heart disease.

PMID- 21897176
TI  - Local infiltration analgesia and other multicomponent techniques to improve
      postoperative outcome--are we comparing oranges and apples?

PMID- 21897177
TI  - The sciatic nerve and knee arthroplasty: to block, or not to block--that is the
      question.

PMID- 21897179
TI  - Absence of proof is not proof of absence.

PMID- 21897180
TI  - Formative assessment of ultrasound-guided regional anesthesia.

PMID- 21897181
TI  - Combination of variations of the interscalene gap as a pitfall for ultrasound
      guided brachial plexus block.

PMID- 21897183
TI  - Transient paraplegia after accidental insertion of an epidural catheter into an
      arachnoid cyst.

PMID- 21897184
TI  - Evidence-based medicine supports ultrasound-guided infraclavicular block over the
      corner pocket supraclavicular technique.

PMID- 21897186
TI  - Neurophysiological changes in deformity correction of adolescent idiopathic
      scoliosis with intraoperative skull-femoral traction.
AB  - STUDY DESIGN: Retrospective review of 36 consecutive patients undergoing coronal
      plane deformity correction with intraoperative skull-femoral traction between
      2005 and 2008 with motor evoked potential (MEP)/somatosensory evoked potential
      monitoring. OBJECTIVE: To determine the prevalence and significance of
      neurophysiological changes with intraoperative skull-femoral traction in
      adolescent idiopathic scoliosis. SUMMARY OF BACKGROUND DATA: Intraoperative
      skeletal traction can be associated with spinal cord stretching and ischemia with
      resultant electrophysiological changes. The prevalence and risks of such changes
      and their clinical significance is unknown. METHODS: Thirty-seven procedures
      involving 36 patients (27 females and 9 males) with a mean age of 14.8 (12-18)
      years were divided into two groups on the basis of the presence (group 1, n = 18
      procedures) or absence (group 2, n = 19) of significant MEP changes with surgery.
      They were compared with patients undergoing correction without traction (group
      3). RESULTS: Significant differences among the groups were observed in mean
      preoperative Cobb angle (86 degrees  vs. 70 degrees  vs. 59 degrees ), mean
      intraoperative posttraction Cobb angle (50.0 degrees  vs. 34.6 degrees ),
      traction index (0.41 vs. 0.50), flexibility index (0.14 vs. 0.27 vs. 0.25), and
      presence of primary lumbar curves (0% vs. 32% vs. 14%). Initial onset of MEP
      amplitude loss (group 1) occurred at a mean of 94 (1-257) minutes from the onset
      of surgery, was bilateral in 13 procedures, and improved at a mean of 5.5 (1-29)
      minutes after decreasing or removing the traction. At closure, complete bilateral
      recovery to baseline was observed in 10 procedures, recovery to >50% baseline in
      five, and recovery to <50% baseline in three procedures. There were no neurologic
      deficits in this series. CONCLUSION: Intraoperative traction is associated with
      frequent changes in MEP monitoring. The thoracic location of the major curve,
      increasing Cobb angle, and rigidity of major curve are significant risk factors
      for changes in MEP with traction. The presence of any MEP recordings irrespective
      of its amplitude at closure was associated with normal neurological function.
      Somatosensory evoked potential monitoring did not correlate with the traction
      induced MEP amplitude changes.

PMID- 21897187
TI  - Does bone morphogenetic protein increase the incidence of perioperative
      complications in spinal fusion? A comparison of 55,862 cases of spinal fusion
      with and without bone morphogenetic protein.
AB  - STUDY DESIGN: Retrospective review of a multi-institutional, multisurgeon
      database. OBJECTIVE: Assess for associations between bone morphogenetic protein
      (BMP) use and rate of complications in spinal fusion. SUMMARY OF BACKGROUND DATA:
      BMP is commonly used in spinal surgery to augment fusion; however, there is
      limited evidence demonstrating its associated complications. METHODS: We
      performed a retrospective analysis of all fusion cases submitted by members of
      the Scoliosis Research Society from 2004 to 2007. We stratified on the basis of
      the use of BMP and evaluated for complications and associated characteristics.
      RESULTS: A total of 55,862 cases of spinal fusion were identified with BMP used
      in 21% (11,933) of the cases. Excluding anterior cervical fusions, there were no
      significant differences between fusions with and without BMP with regard to
      overall complications (8.4% vs. 8.5%; P = 0.5), wound infections (2.4% vs. 2.4%;
      P = 0.8), or epidural hematomas/seromas (0.2% vs. 0.2%; P = 0.3). Anterior
      cervical fusions with BMP were associated with more overall complications (5.8%
      vs. 2.4%; P < 0.001) and more wound infections (2.1% vs. 0.4%; P < 0.001) than
      fusions without BMP. On multivariate analysis for thoracolumbar and posterior
      cervical fusions, BMP use was not a significant predictor of complications (P =
      0.334; odds ratio = 1.039; 95% confidence interval = 0.961-1.124; covariates were
      BMP use, patient age, revision vs. primary surgery). Multivariate analysis for
      anterior cervical spinal fusion demonstrated that BMP use remained a significant
      predictor of complications (P < 0.001, odds ratio = 1.6; 95% confidence interval
      = 1.516-1.721), after adjusting for the effects of patient age and whether the
      surgery was a revision procedure. CONCLUSION: BMP use with anterior cervical
      fusion was associated with an increased incidence of complications. Use of BMP
      was not associated with more complications in thoracolumbar and posterior
      cervical fusions.

PMID- 21897188
TI  - Instrumentation constructs in pediatric patients undergoing deformity correction
      correlated with Scoliosis Research Society scores.
AB  - STUDY DESIGN: Data collected prospectively from the Prospective Pediatric
      Scoliosis Study (PPSS) were analyzed statistically to address the hypothesis that
      covered specific aspects of treatment and its outcome. OBJECTIVE: To assess and
      contrast Scoliosis Research Society (SRS) outcome scores for patients assigned to
      one of three types of spinal instrumentation constructs. The study hypothesis was
      that the instrumentation strategy that provides the best curve correction will be
      associated with the best SRS scores. SUMMARY OF BACKGROUND DATA: Surgical
      treatment of scoliosis has evolved over time using implants and surgical
      techniques; however, quality of life indicators have not typically been analyzed
      to assess whether surgery and instrumentation will improve quality of life in
      pediatric patients. METHODS: Patients were assigned to one of three
      instrumentation groups depending on the type of construct used. The Scoliosis
      Research Society's SRS-30 survey was used to measure patient outcomes comparing
      preoperative results to a 2-year follow-up. RESULTS: Changes in the SRS Pain,
      Activity, Appearance, Mental, Satisfaction, and SRS Total domains did not differ
      significantly among instrumentation groups for any time intervals. However,
      analysis of SRS Pain did show a significant change over time for all
      instrumentation patterns. The analysis of SRS Activity showed a significant
      change over time for all instrumentation patterns preoperatively to 2 years
      postoperatively. Analysis of SRS Appearance showed a significant change over time
      for all groups but no difference between instrumentation groups. The analysis of
      SRS Mental based on instrumentation types showed a significant change over time,
      but only the pedicle screw group's change was statistically significant. Finally,
      analysis of SRS Satisfaction by instrumentation type showed a statistically
      significant change over time for all instrumentation patterns. CONCLUSION: There
      were no statistically significant baseline differences among the three
      instrumentation construct groups based on mean scores for the six SRS domains.
      None of the SRS domains had differences among the instrumentation constructs in
      change scores or significant differences among the instrumentation constructs.

PMID- 21897189
TI  - DNA identification in mass fatality incidents.
AB  - DNA identification has become an important aspect of mass fatality management as
      well as in other instances of difficult identification of human remains. Most
      large mass fatality incidents will require DNA identification. Medical examiners
      should prepare for such potential eventuality. Whether DNA is tested, in mass
      fatality incidents, DNA specimens should be obtained from remains as well as from
      next-of-kin for potential testing. DNA identification is neither as slow nor as
      expensive relative to the overall fatality management as is commonly assumed.
      This article sought to provide medical examiners with a framework for DNA
      identification in mass fatality incidents.

PMID- 21897190
TI  - Deaths due to jambia-inflicted lesions in a domestic environment.
AB  - Domestic violence is a significant health problem affecting women all around the
      world by causing a wide range of physical and psychological traumas. Yemen has a
      very high percentage of women experiencing intimate partner violence (up to 50%)
      and a high mortality rate. In this article, we are presenting 3 particular cases
      of domestic violence deaths in which the weapon used was a jambia (jambia,
      jambiah, jambiya, djambia), a special dagger specific to Yemen and the
      surrounding areas. We are also summarizing the main characteristics of jambia
      inflicted lesions and their thanatology.

PMID- 21897191
TI  - An unusual suicide case by combination of choking and hanging.
AB  - A 40-year-old man was found dead in his prison cell, hanging on a twisted bandage
      tightened around his neck. His permanent metal tracheostomy tube was completely
      corked with a piece of paper wrapped with transparent cellophane from a cigarette
      case. After police investigation and complete autopsy, suicide was determined as
      the manner of death. Although suicides by 1 form of asphyxia are relatively
      common, combination of several different forms of asphyxia is far less frequent.
      We present this unusual and very rare case of suicide by combination of 2 forms
      of asphyxia, that is, choking and hanging, along with autopsy findings and
      discussion.

PMID- 21897192
TI  - Regarding state of the art in forensic investigation of sudden cardiac death by
      Oliva et al: a suggestion for a method of opening the heart to enable
      preservation of a Chiari web.

PMID- 21897193
TI  - Evaluation of histologic changes of the skin in postmortem period.
AB  - Determination of the time of death is an important consideration in forensic
      practice. Many methods have been attempted to accurately and systematically
      determine the postmortem interval (PMI). Histologic examination of the skin or
      appendages is one of the methods tried by few researchers. However, no attempt
      had been made to analyze the histologic changes in the skin and appendages
      simultaneously and to compare them with PMI. We sequentially studied the
      histologic changes of the skin and appendages in the early PMI. The results of
      the present study show that the skin undergoes progressive morphological changes
      in the postmortem period. The epidermis and the dermis appeared normal for 6
      hours after death, and after this period, degenerative changes began. By 6 to 9
      hours after death, degeneration began in the dermis, and by the end of 18 hours,
      the dermis began to disintegrate. The sweat glands appeared normal for
      approximately 3 to 4 hours. For 18 hours after death, the sebaceous glands and
      hair follicles appeared normal, and after this period, degeneration began.

PMID- 21897194
TI  - Bladder rupture after intentional medication overdose.
AB  - We report the case of a 51-year-old woman who had a medical history of diabetes,
      depression with past suicide attempts, and suicidal ideation. She was found
      unresponsive in a motel with multiple bottles of medicines (melatonin,
      carisoprodol, ativan, and clonazepam) and an unopened bottle of wine. She was
      transported to the local hospital and treated for benzodiazepine toxicity and
      aspiration pneumonitis.The decedent gradually became more alert and was extubated
      3 days after hospital admission. The decedent was reportedly getting up to use
      the restroom when she became tachypneic and diaphoretic and complained of
      generalized body pain. Her condition quickly declined, and she was pronounced
      deceased. A postmortem examination revealed an acute bladder rupture and soft
      tissue hemorrhage.A review of the literature reveals that isolated bladder
      rupture after minimal or no trauma in association with alcohol or drug ingestion
      is an infrequently reported, but recognized, injury. The diagnosis of bladder
      rupture should be considered in a patient with lower abdominal pain, even without
      a history of trauma. A history of voiding or bladder dysfunction should increase
      the suspicion for this injury. If suspected, a retrograde cystogram should be
      obtained promptly. Failure to consider and recognize this injury may lead to
      significant morbidity.

PMID- 21897195
TI  - Will virtual autopsy technology replace the role of forensic pathologist in the
      future?

PMID- 21897196
TI  - Decapitation due to car accident.
AB  - The occurrence of complete decapitation as a consequence of car accident is an
      extremely rare event. This fatality is generally seen in pedestrians run over by
      trains and also in motorcyclists who impact against the tailboard of trucks.
      Moreover, complete transection of pedestrians and occupants of cars has been
      described in road accidents especially in case of vehicles traveling at a high
      speed. We present a case of decapitation with complete degloving injury of the
      neck in a patient involved in a traffic accident, and we briefly discuss the
      possible mechanisms producing this injury.

PMID- 21897197
TI  - A proposal to minimize work area contamination during induction.

PMID- 21897198
TI  - Comment on "A rising ioPTH level immediately after parathyroid resection: are
      additional hyperfunctioning glands always present? An application of the
      Wisconsin Criteria".

PMID- 21897199
TI  - Preoperative hypoalbuminemia is an independent risk factor for the development of
      surgical site infection following gastrointestinal surgery.

PMID- 21897200
TI  - Predicting risk for serious complications with bariatric surgery: results from
      the Michigan Bariatric Surgery Collaborative.
AB  - OBJECTIVES: To develop a risk prediction model for serious complications after
      bariatric surgery. BACKGROUND: Despite evidence for improved safety with
      bariatric surgery, serious complications remain a concern for patients, providers
      and payers. There is little population-level data on which risk factors can be
      used to identify patients at high risk for major morbidity. METHODS: The Michigan
      Bariatric Surgery Collaborative is a statewide consortium of hospitals and
      surgeons, which maintains an externally-audited prospective clinical registry. We
      analyzed data from 25,469 patients undergoing bariatric surgery between June 2006
      and December 2010. Significant risk factors on univariable analysis were entered
      into a multivariable logistic regression model to identify factors associated
      with serious complications (life threatening and/or associated with lasting
      disability) within 30 days of surgery. Bootstrap resampling was performed to
      obtain bias-corrected confidence intervals and c-statistic. RESULTS: Overall, 644
      patients (2.5%) experienced a serious complication. Significant risk factors (P <
      0.05) included: prior VTE (odds ratio [OR] 1.90, confidence interval [CI] 1.41
      2.54); mobility limitations (OR 1.61, CI 1.23-2.13); coronary artery disease (OR
      1.53, CI 1.17-2.02); age over 50 (OR 1.38, CI 1.18-1.61); pulmonary disease (OR
      1.37, CI 1.15-1.64); male gender (OR 1.26, CI 1.06-1.50); smoking history (OR
      1.20, CI 1.02-1.40); and procedure type (reference lap band): duodenal switch (OR
      9.68, CI 6.05-15.49); laparoscopic gastric bypass (OR 3.58, CI 2.79-4.64); open
      gastric bypass (OR 3.51, CI 2.38-5.22); sleeve gastrectomy (OR 2.46, CI 1.73
      3.50). The c-statistic was 0.68 (bias-corrected to 0.66) and the model was well
      calibrated across deciles of predicted risk. CONCLUSIONS: We have developed and
      validated a population-based risk scoring system for serious complications after
      bariatric surgery. We expect that this scoring system will improve the process of
      informed consent, facilitate the selection of procedures for high-risk patients,
      and allow for better risk stratification across studies of bariatric surgery.

PMID- 21897201
TI  - The effect of tricyclic antidepressants on cutaneous melanoma cell lines and
      primary cell cultures.
AB  - The tricyclic antidepressants have previously been shown to exert activity
      against glioma cells in vitro. Initial studies in cell lines suggested that this
      might extend to melanoma cells. We have therefore conducted a study in primary
      cell cultures from metastatic cutaneous melanoma deposits using a well
      established ATP-based tumour chemosensitivity assay to confirm and extend these
      findings. Two cell lines and eight primary cell cultures from metastatic melanoma
      deposits were exposed to three tricyclic drugs, amitriptyline, nortriptyline and
      clomipramine, at concentrations ranging from 200 to 6.25 umol/l in the ATP-based
      tumour chemosensitivity assay. All three drugs showed activity, although
      nortriptyline was more active than clomipramine or amitriptyline in both cell
      lines and primary cell cultures, with an IC50 of 9, 27 and 33 umol/l,
      respectively. Tricyclic agents show activity against melanoma in vitro. This
      could be related to the lysosomal effects based on their cationic amphiphilic
      properties, or effects at the mitochondrial membrane.

PMID- 21897202
TI  - Gypenosides improve cognitive impairment induced by chronic cerebral
      hypoperfusion in rats by suppressing oxidative stress and astrocytic activation.
AB  - Gypenosides (GP), the saponin extract derived from the Gynostemma pentaphyllum
      Makino, a widely reputed medicinal plant in China, has been reported to have some
      neuroprotective effects. We used a rat model of chronic cerebral hypoperfusion to
      investigate the protective effects of GP on the cortex and hippocampal CA1 region
      and the underlying mechanisms for its inhibition of cognitive decline. Daily
      doses of 100 and 200 mg/kg GP were orally administered to adult male Sprague
      Dawley rats for 61 days after inducing cerebral hypoperfusion experimentally, and
      spatial learning and memory were assessed using the Morris water maze.
      Antioxidative capability was measured biochemically. The levels of lipid
      peroxidation and oxidative DNA damage were assessed by immunohistochemical
      staining for 4-hydroxynonenal and 8-hydroxy-2'-deoxyguanosine, respectively.
      Activated astrocytes were assessed by immunohistochemical staining and western
      blotting with GFAP antibodies. Rats receiving 200 mg/kg GP had better spatial
      learning and memory than saline-treated rats. GP 200 mg/kg/day were found to
      markedly enhance antioxidant abilities, decrease lipid peroxide products and
      oxidative DNA damage, and reduce the activation of inflammatory astrocytes.
      However, GP 100 mg/kg had no significant effects. GP may have therapeutic
      potential for the treatment of dementia induced by chronic cerebral hypoperfusion
      and further evaluation is warranted.

PMID- 21897203
TI  - Behavioral satiety sequence in a genetic mouse model of obesity: effects of
      ghrelin receptor ligands.
AB  - Behavioral satiety sequence (BSS) is a useful paradigm to assess the effects of
      orexigenic and anorexigenic profiles of novel pharmacological and genetic
      manipulations in rodents. To date, no studies have described the satiety profile
      of leptin-deficient ob/ob mice, an important animal model of obesity in this
      task. Furthermore, no studies have described changes in the BSS after treatment
      with ghrelin receptor ligands, which have become an attractive therapeutic target
      in obesity drug discovery efforts. BSS testing was carried out in ob/ob mice and
      their lean controls. After baseline analysis, effects of ghrelin (2 nmol/10 g)
      and of the ghrelin receptor antagonist (D-Lys)-GHRP-6 (66.6 and 133.3 nmol/10 g)
      were studied in BSS in mice of both genotypes. The baseline BSS profile of ob/ob
      mice showed an increased eating and a decreased resting activity. Ob/ob mice
      presented with a decreased sensitivity to the stimulation with ghrelin and with
      the ghrelin receptor antagonist, which caused strong anorexic and adverse side
      effects in lean mice, thereby disrupting the BSS profile. BSS is an indispensable
      tool for parsing the role of the ghrelinergic system in satiety, to characterize
      transgenic mice and to elicit behavioral feeding profiles of novel anorectic
      agents.

PMID- 21897204
TI  - Cue effects on methylphenidate self-administration in rats.
AB  - Associations between drugs and the stimuli paired with drugs have been proposed
      as primary factors in drug addiction and relapse. Previous research has found
      cues paired with drug infusions are important for many classes of drugs. The
      purpose of the present experiment was to determine if a cue light was necessary
      to engender reliable self-administration of methylphenidate (MPH), which is a
      widely prescribed drug for attention deficit hyperactivity disorder. Rats were
      given access to MPH (0.3 mg/kg/infusion) or saline for self-administration. Half
      of the rats in each group had infusions paired with a cue light, whereas the
      other half did not. Two additional groups of rats received MPH infusions
      noncontingently; one group's lever pressing turned on the cue light, and the
      other group's lever pressing had no consequence. Both MPH and the cue functioned
      as weak reinforcers on their own. The group that lever pressed for MPH paired
      with a cue light pressed significantly more for MPH than any other group,
      indicating that the cue and MPH had a synergistic effect on self-administration
      when combined. Taken together, these results indicate that MPH has reinforcing
      properties on its own, but that environmental cues also play an important role in
      enhancing MPH self-administration.

PMID- 21897206
TI  - Low thrombogenicity of calcified atherosclerotic plaques is associated with bone
      morphogenetic protein-2-dependent inhibition of tissue factor expression.
AB  - Morphology of atherosclerotic plaque is a major determinant of plaque
      thrombogenicity. Calcified atherosclerotic lesions are less prone to thrombosis
      and contain less tissue factor (TF) than lipid-rich plaques. Although bone
      morphogenetic protein (BMP)-2 is a known mediator of vascular calcification, the
      role of BMP-2 in the regulation of plaque thrombogenicity has not been
      established. We hypothesized that the expression of BMP-2 within highly calcified
      atherosclerotic plaques inhibits TF expression and reduces thrombogenicity of
      calcified lesions. In the present study, we measured levels of TF and BMP-2 in
      human calcified and lipid-rich carotid plaques and studied the effects of BMP-2
      on TF expression in human monocytes in vitro. Quantitative immunohistochemical
      analysis of endarterectomy specimens for TF and BMP-2 revealed that calcified
      plaques contained nearly three-times less TF antigen than lipid-rich ones. In
      contrast, calcified plaques expressed two-times more BMP-2 antigen than lipid
      rich lesions. BMP-2 markedly decreased protein expression and surface
      redistribution of TF in activated human monocytes in vitro. BMP-2-mediated
      inhibition of TF expression in monocytes/macrophages could contribute to reduced
      thrombogenicity of calcified atherosclerotic plaques.

PMID- 21897205
TI  - Importance of associative learning processes for one-trial behavioral
      sensitization of preweanling rats.
AB  - During adulthood, associative learning is necessary for the expression of one
      trial behavioral sensitization; however, it is uncertain whether the same
      associative processes are operative during the preweanling period. Two strategies
      were used to assess the importance of associative learning for one-trial
      behavioral sensitization of preweanling rats. In the initial experiments, we
      varied both the sequence and time interval between presentation of the
      conditioned stimulus (CS, novel environment) and unconditioned stimulus (US,
      cocaine). In the final experiment, we determined whether electroconvulsive shock
      induced retrograde amnesia would disrupt one-trial behavioral sensitization.
      Results showed that robust-sensitized responding was apparent regardless of the
      sequence in which cocaine and the novel environment (the presumptive CS) were
      presented. Varying the time between CS and US presentation (0, 3, or 6 h) was
      also without effect. Results from experiment 3 showed that single or multiple
      electroconvulsive shock treatments did not alter the expression of the sensitized
      response. Therefore, these data indicated that one-trial behavioral sensitization
      of preweanling rats was exclusively mediated by nonassociative mechanisms and
      that associative processes did not modulate sensitized responding. These findings
      are in contrast to what is observed during adulthood, as adult rats exhibit one
      trial behavioral sensitization only when associative processes are operative.

PMID- 21897207
TI  - Diagnostic performance of quantitative fecal immunochemical test and multivariate
      prediction model for colorectal neoplasms in asymptomatic individuals.
AB  - OBJECTIVE: Quantitative fecal immunochemical test (QTFIT) has the advantage of
      being able to describe test characteristics on a scaled rather than binary
      system. The aims of this study were to decide the optimal cut-off points of QTFIT
      and to make a multivariate prediction model for colorectal neoplasms in
      asymptomatic adults. MATERIALS AND METHODS: We retrospectively analyzed 1085
      consecutive asymptomatic individuals who completed both full colonoscopy and
      QTFIT at a general health checkup clinic. Advanced adenomatous polyps (AP) were
      defined as APs of at least 1 cm in diameter; adenomas with villous component or
      high-grade dysplasia; and significant neoplasia (SN) including both advanced AP
      and colorectal cancer. RESULTS: The ideal cut-off value of QTFIT was chosen based
      on a value that maximized the sum of both sensitivity and specificity, and
      clinical utility. For AP, 25 ng/ml was chosen as the optimal cut-off value and
      provided a sensitivity of 31% [95% confidence interval (CI): 27-36] and
      specificity of 79% (95% CI: 76-82). For SN, the ideal QTFIT cut-off value was 25
      ng/ml, providing a sensitivity of 51% (95% CI: 39-62) and specificity of 77% (95%
      CI: 74-80). For colorectal cancer, the optimal cut-off point was 50 ng/ml,
      offering a sensitivity of 75% (95% CI: 41-93) and specificity of 86% (95% CI: 85
      86). The multivariate prediction model was represented by nomogram and was
      validated by bootstrap method. CONCLUSION: The diagnostic performance of QTFIT
      for CRC is promising, although its sensitivity for AP and SN is unsatisfactory.
      BMI, in addition to age and sex improves the accuracy of SN screening by QTFIT.

PMID- 21897208
TI  - Can blood pressure measurements taken in the physician's office avoid the 'white
      coat' bias?
AB  - OBJECTIVE: Obtaining an accurate blood pressure (BP) reading is vital for
      diagnosing hypertension. However, BP measures taken in the physician's clinic
      (CBP) are subject to the 'white coat' bias. Measurements taken outside the office
      using ambulatory (ABP) and home (HBP) monitoring are superior predictors of
      cardiovascular diseases compared with CBP, but ABP remains underutilized because
      of the effort and expense involved. Unfortunately, HBP has limitations, including
      questionable device validity and patient compliance. Thus, it is important to
      identify feasible alternative techniques to measure BP in the office that will
      increase the accuracy of the diagnosis. METHODS: Auscultatory BP was measured in
      249 patients in a nonclinical setting by trained technicians (NCBP); on the
      following day, patients were taken to their physician (CBP). They were also given
      an HBP monitor, and a 36 h ABP monitoring. Because ABP is considered the gold
      standard for prediction of cardiovascular disease, these readings were used as
      the criterion in a statistical model in which CBP, HBP, and NCBP were entered as
      predictors. The level of agreement between measurements was estimated. RESULTS:
      Multiple regression analysis showed that HBP and NCBP (P < 0.001) explained 94
      and 87% of the variance in systolic and diastolic ABP, respectively. The
      agreement between NCBP and ABP was greater than that between CBP and ABP or
      between HBP. CONCLUSION: When ABP monitoring and HBP monitoring are not options,
      the NCBP at the clinic can avoid the white coat bias and therefore improve
      diagnosis.

PMID- 21897209
TI  - What's it like when you find eating difficult: children's and parents'
      experiences of food intake.
AB  - BACKGROUND: Despite significant advances in supportive care, children and
      families continue to face many challenges managing the consequences of cancer
      therapies. The purpose of this study was to explore the eating experiences of
      children, both at home and in hospital. OBJECTIVE: The objective of the study was
      to explore the perceptions and experiences of children and their families
      regarding food intake and discover how nutritional issues are managed by children
      and families. METHODS: A stratified sample was recruited according to stage in
      treatment journey, risk of developing nutritional problems, and aged 4 to 12
      years undergoing chemotherapy at a cancer center in London, was recruited. This
      qualitative study involved the use of 2 key visual storytelling techniques: (1)
      photographs and drawings contained in a scrapbook or diary used as interview
      stimuli and (2) in-depth interviews with parents. RESULTS: Our study revealed a
      complex interplay between the context of care, added to an individual child's
      desires and nutritional needs that are constantly changing during therapy.
      Failures in the hospital system to meet the nutritional needs of children placed
      extra stress on parents to provide food for their children. CONCLUSIONS: A
      relaxed and creative approach to tempting and keeping children engaged with food
      and eating was a focus for parents, which avoided what they described as making a
      "big deal about it." Poor information meant that children and parents were not
      always prepared for the adverse effects of therapies. IMPLICATIONS FOR PRACTICE:
      This study contributes much to the emerging description of practice guidance and
      informs strategies that can be used by children and parents.

PMID- 21897210
TI  - Patient and family caregiver decision making in the context of advanced cancer.
AB  - BACKGROUND: A basic tenet of palliative care is to maintain an individual's
      control over the dying process. However, when decline occurs quickly, as may be
      the case in advanced cancer, transition of responsibility for illness management
      to a family caregiver may become necessary when care takes place in the home.
      OBJECTIVE: The aim of this study was to understand the decision-making process
      that occurs between a dying individual and his or her family caregiver. METHODS:
      Participants in this grounded theory study were selected by purposive and
      theoretical sampling methods. Data were collected and analyzed using a constant
      comparison approach. RESULTS: The core category covering captured the inordinate
      efforts taken by informal caregivers to ensure that their family member would be
      able to die in the manner of his or her choosing. The basic social process,
      dancing on the stairs, chronicled the families' decision-making process as they
      navigated through this delicate and precarious end stage of life. CONCLUSIONS:
      Dancing on the stairs required a close relationship between 2 people who were
      willing to remain engaged with each other, despite the difficulties they faced.
      This decision-making process may be applicable to other health care transitions
      in people's lives that need to be managed with another person. IMPLICATIONS FOR
      PRACTICE: Palliative care education for nurses in all care health settings may
      ease transitions for end-stage patients. Health promotion initiatives designed to
      educate the lay public about advance directives and end-stage illness management
      in a home setting may help to prepare family caregivers for their future
      responsibilities.

PMID- 21897211
TI  - Breast cancer and symptom clusters during radiotherapy.
AB  - BACKGROUND: Symptom clusters assessment shifts the clinical focus from a specific
      symptom to the patient's experience as a whole. Few studies have examined breast
      cancer symptom clusters during treatment, and fewer studies have addressed
      symptom clusters during radiation therapy (RT). The theoretical underpinning of
      this study is the Symptoms Experience Model. Research is needed to identify
      antecedents and consequences of cancer-related symptom clusters. OBJECTIVE: The
      present study was intended to determine the clustering of symptoms during RT in
      women with breast cancer and significant correlations among the symptoms,
      individual characteristics, and mood. METHODS: A secondary data analysis from a
      descriptive correlational study of 93 women at weeks 3 to 7 of RT from centers in
      the mid-Atlantic region of the United States, Symptom Distress Scale, the
      subscales of the Positive and Negative Affect Scale, Life Orientation Test, and
      Self-transcendence Scale were completed. RESULTS: Confirmatory factor analysis
      revealed symptoms grouped into 3 distinct clusters: pain-insomnia-fatigue,
      cognitive disturbance-outlook, and gastrointestinal. The pain-insomnia-fatigue
      and cognitive disturbance-outlook clusters were associated with individual
      characteristics, optimism, self-transcendence, and positive and negative mood.
      The gastrointestinal cluster correlated significantly only with positive mood.
      CONCLUSIONS: This study provides insight into symptoms that group together and
      the relationship of symptom clusters to antecedents and mood. IMPLICATIONS FOR
      PRACTICE: These findings underscore the need to define and standardize the
      measurement of symptom clusters and understand variability in concurrent
      symptoms. Attention to symptom clusters shifts the clinical focus from a specific
      symptom to the patient's experience as a whole and helps identify the most
      effective interventions.

PMID- 21897212
TI  - Participant perceptions of a mindful movement program for older women with breast
      cancer: focus group results.
AB  - BACKGROUND: Little attention has been directed to the longer-term survivorship
      phase for older breast cancer survivors (BCSs) who often continue to struggle
      with late and long-term adverse effects of treatment including lower physical
      functioning, fear of recurrence, stress and anxiety, neuropathies, and pain.
      Creative and accessible strategies are needed that offer support to this
      population of cancer survivors. OBJECTIVE: The purpose of this study was to
      examine participant perceptions of the effects of a Mindful Movement Program
      intervention on quality of life and mindfulness through focus groups. This was
      part of a pilot feasibility study testing the intervention with older women at
      more than 1 year after treatment for breast cancer. METHODS: Eight to 9 weeks
      after completion of 12 weekly, 2-hour mindful movement sessions, focus groups
      were held with 3 experimental group cohorts of participants who had attended on
      average 10.4 classes. Focus group interviews were recorded, transcribed verbatim,
      and analyzed using qualitative techniques for recurrent themes. RESULTS: Four
      themes emerged from the direct quotes of the participants: freedom,
      rediscovering, body sense in moving, and in the moment. Participants also
      contributed opinions about program delivery. CONCLUSIONS: Participants described
      how the Mindful Movement Program experience affected their lives. Their feedback
      indicated that the intervention yielded positive results and was feasible for a
      variety of older BCSs. IMPLICATIONS FOR PRACTICE: Research with a wider group of
      participants is needed. Preliminary indications are that mindful movement may
      offer an acceptable strategy for increasing activity and decreasing stress among
      older BCSs.

PMID- 21897213
TI  - Simvastatin displays an antioxidative effect by inhibiting an increase in the
      serum 8-isoprostane level in patients with acute ischemic stroke: brief report.
AB  - OBJECTIVES: Oxidative stress plays an important role in ischemic stroke
      pathophysiology. Some drugs are known to have a substantial influence on
      oxidative stress. In this study, we examined the antioxidant effect of
      simvastatin through its influence on patients' serum 8-isoprostane levels.
      METHODS: We measured serum 8-isoprostane levels in 67 patients with acute
      ischemic stroke treated and not treated with simvastatin within 5 days after
      stroke onset, in comparison with 20 normal controls. RESULTS: Stroke patients
      from both groups had significantly higher initial serum 8-isoprostane levels than
      the controls. The median value of serum 8-isoprostane level was significantly
      lower in the simvastatin-treated group after 5 days of treatment. CONCLUSIONS:
      The results confirm the contribution of oxidative stress to brain ischemia and
      suggest antioxidative properties of statins in the acute phase of ischemic stroke
      patients.

PMID- 21897214
TI  - Ambulatory anesthesia aspects for tonsillectomy and abrasion in children.
AB  - PURPOSE OF REVIEW: Tonsillectomy is a very common procedure, but with risks or
      challenges, both for the surgeon and anesthesiologist. Many places have
      considerable experience and expertise with this procedure, and a lot of clinical
      studies are continuously being presented. RECENT FINDINGS: Most preoperative
      aspects are covered, including indications, preoperative risk assessment,
      premedication, anesthetic induction and maintenance, as well as recovery function
      and side-effects; such as bleeding, agitation, pain, nausea and sleep apnea.
      Controversies exist as to ambulatory versus in-patient care, laryngeal mask
      airway versus endotracheal intubation, use of local anesthetic infiltration and
      use of glucocorticoids. SUMMARY: Preoperative evaluation should identify
      increased bleeding risk, potential airway problems, ongoing infection and
      symptoms of obstructive sleep apnea.Intravenous propofol is most often used for
      anesthetic induction, although inhalational sevoflurane is a valid alternative.
      Laryngeal mask airway or endotracheal tube may both be used safely and
      effectively; the choice will depend upon the routine and experience of the team.
      Paracetamol and NSAIDs are useful baseline medication for nonopioid multimodal
      postoperative pain treatment and prophylaxis. Similar with local anesthesia
      infiltration and dexamethasone medication, although somewhat more disputed.
      Dexamethasone is also useful for nausea/vomiting prophylaxis, together with
      ondansetron and also propofol for anesthesia maintenance.

PMID- 21897215
TI  - Ultrasound brachial plexus anesthesia and analgesia for upper extremity surgery:
      essentials of our current understanding, 2011.
AB  - PURPOSE OF REVIEW: Ultrasound-guidance is gaining tremendous popularity. There is
      growing evidence of value with emphasis on clinical relevance, but can ultrasound
      guidance scientifically warrant changing the practice of upper extremity
      regional? The literature is searched to describe findings where ultrasound may
      reduce complication rates, reduce block performance times, and improve block
      efficacy and quality. RECENT FINDINGS: Ultrasound examination identified
      variations in anatomical positioning of C5-C7 roots in approximately half of all
      patients despite no deleterious effects on block efficacy. Anesthetic volumes in
      brachial plexus blockade may be reduced without compromise of effectiveness.
      However, even with reduced volumes injected into the interscalene space,
      respiratory compromise from effect(s) on the phrenic nerve may result in hemi
      diaphragmatic paresis. Ultrasound-guidance may reduce discomfort during axillary
      block placement compared with neurostimulation or parasthesia. Nerve catheters
      may be highly effective and provide prolonged analgesia compared with single-shot
      injections. Infraclavicular catheters result in improved analgesia compared with
      supraclavicular catheters and multiple injections of local provide no advantage
      over single-shot infraclavicular blockade. Dexamethasone combined with local may
      extend analgesia following a single-injection interscalene or supraclavicular
      block. During interscalene blockade, intraepineurial injections may occur, but
      incidence of nerve injury remains low. Therefore, debate continues about
      intraepineurial injections. SUMMARY: Intraepineurial injection requires
      additional investigation. Conclusions have suggested reducing typical volumes (40
      ml) of local with ultrasound-directed upper extremity blockade. Increased use of
      perineural catheters is being advocated for prolonged analgesia, but risk-to
      benefit consequences need to always be considered.

PMID- 21897216
TI  - Lessons learned from the SYNTAX trial for multivessel and left main stem coronary
      artery disease.
AB  - PURPOSE OF REVIEW: The SYNergy between percutaneous coronary intervention with
      TAXus and cardiac surgery (SYNTAX) trial is the most important trial of surgery
      and stents in patients with severe coronary artery disease (CAD) and reflects
      real clinical practice. This review describes its key findings at 3 years with
      particular reference to what is already known on this topic. RECENT FINDINGS:
      Taking together the SYNTAX randomized trial and its registry component, almost
      79% of patients with three-vessel CAD and almost two-thirds of patients with left
      main stem (LMS) disease have a survival benefit and marked reduction in the need
      for repeat revascularization with coronary artery bypass grafting (CABG) in
      comparison to stents, implying that CABG is still the treatment of choice for
      most of these patients. This conclusion, at odds with results of previous trials
      of stenting and surgery but consistent with findings of large propensity-matched
      registries, can be explained by the fact that SYNTAX enrolled 'real life'
      patients rather than the highly select patients in previous trials. SYNTAX also
      shows that for patients with less severe CAD there is no difference in survival
      between CABG and stents but a lower incidence of repeat revascularization with
      CABG. SUMMARY: The results of the SYNTAX trial confirm that at 3 years CABG
      remains the treatment of choice for most patients with three-vessel and LMS
      disease and especially in those with the most severe disease. SYNTAX will have a
      profound effect on practice recommendations for the foreseeable future and
      already has had a major effect on the new European Society for
      Cardiology/European Association for Cardiothoracic Surgery guidelines for
      myocardial revascularization.

PMID- 21897217
TI  - Guided transfer of critically ill patients:  where patients are transferred can
      be an informed choice.
AB  - PURPOSE OF REVIEW: Given increasingly scarce healthcare resources and highly
      differentiated hospitals, with growing demand for critical care, interhospital
      transfer is an essential part of the care of many patients. The purpose of this
      review is to examine the extent to which hospital quality is considered when
      transferring critically ill patients, and to examine the potential benefits to
      patients of a strategy that incorporates objective quality data into referral
      patterns. RECENT FINDINGS: Interhospital transfer of critically ill patients is
      now common and safe. Although extensive research has focused on which patients
      should be transferred and when they should be transferred, recent study has
      focused on where patients should be transferred. Yet, the choice of destination
      hospital is rarely recognized as a therapeutic choice with implications for
      patient outcomes. The recent public release of high-quality, risk-adjusted and
      reliability-adjusted outcome data for most hospitals now offers physicians an
      informed basis on which to choose to which destination hospital a patient should
      be transferred. A strategy of 'guided transfer' that integrates public quality
      information into critical care transfer decisions is now feasible. SUMMARY:
      Although hospitals often transfer patients, there may be substantial room for
      improvement in transfer patterns. Guiding transfers on the basis of objective
      quality information may offer substantial benefits to patients, and could be
      incorporated into quality improvement initiatives.

PMID- 21897218
TI  - Mechanical assistance of the circulation during cardiogenic shock.
AB  - PURPOSE OF REVIEW: Cardiogenic shock still has a grave prognosis. We present the
      recent advances in mechanical circulatory support (MCS) for the treatment of
      refractory cardiogenic shock. RECENT FINDINGS: The contraindications for short
      term MCS in rapid-onset cardiogenic shock are becoming fewer and the threshold
      for its application has been progressively lowered. Short-term MCS is
      increasingly used in refractory cardiac arrest and will be probably integrated as
      the last means in the advanced cardiopulmonary resuscitation algorithm (provided
      there is experienced team and technical support). Improved device technology has
      contributed to improved results of long-term MCS. Emergent application of long
      term MCS in patients with critical cardiogenic shock after a long history of
      progressively deteriorating end-stage chronic heart failure should be interpreted
      as delayed application associated with increased mortality. SUMMARY: Although MCS
      can be life saving in cardiogenic shock, the results are still suboptimal.
      Mortality is associated with the critical presupport state and the adverse events
      during MCS. Early initiation of support that meets the patient's requirements,
      potent support in the early phase, adverse event prevention, global combined
      management (surgical, interventional, medical), balanced support duration,
      bridging to further therapeutic modalities including heart transplantation or
      longer-term support, and advanced technology could offer improved results.

PMID- 21897219
TI  - Recent insights into racial differences in bone and mineral metabolism.
AB  - PURPOSE OF REVIEW: This study reviews recent insights into racial differences in
      bone from 2010 to 2011. RECENT FINDINGS: Recent studies have focused on expanding
      our current understanding of responsible mechanisms for racial differences in
      osteoporotic fracture risk. Using newer, three-dimensional imaging techniques,
      these studies demonstrated that racial differences in bone mass and structure are
      apparent early in adolescence, even when accounting for differences in bone size
      and muscle mass by race. In addition, recent studies using genetic admixture
      analysis showed that greater percentage of African admixture was independently
      associated with higher bone mass and more favorable parameters of bone strength
      in children and adults. Furthermore, recent studies showed that the relationships
      between 25-hydoxyvitamin D and bone outcomes differed by race, with lower 25
      hydroxyvitamin D levels being associated with lower bone quality and higher
      fracture risk in whites but not blacks. SUMMARY: Racial differences in bone mass
      and strength are apparent early in life, are independently associated with
      genetic ancestry, and may be partly explained by differences in the relationships
      between vitamin D and bone metabolism. Further studies are needed to explore
      these findings, with the ultimate goal of better defining molecular and cellular
      mechanisms underlying racial differences in bone quality.

PMID- 21897220
TI  - Bone health in anorexia nervosa.
AB  - PURPOSE OF REVIEW: Anorexia nervosa is associated with low bone mineral density
      (BMD), concerning for an increased risk of fractures, and decreased bone accrual
      in adolescents, concerning for suboptimal peak bone mass. This review discusses
      causes of impaired bone health in anorexia nervosa and potential therapeutic
      strategies. RECENT FINDINGS: Low BMD in anorexia nervosa is consequent to
      decreased lean mass, hypogonadism, low insulin-like growth factor-1 (IGF-1),
      relative hypercortisolemia and alterations in hormones impacted by energy
      availability. Weight gain causes some improvement in bone accrual, but not to the
      extent observed in controls, and vitamin D supplementation does not increase BMD.
      Oral estrogen is not effective in increasing BMD, likely from IGF-1 suppressive
      effects. In contrast, transdermal estrogen replacement is effective in increasing
      bone accrual in adolescents with anorexia nervosa, although not to the extent
      seen in controls. Recombinant human IGF-1 increases bone formation in
      adolescents, and with oral estrogen increases BMD in adults with anorexia
      nervosa. Bisphosphonates increase BMD in adults, but not in adolescents, and
      should be used cautiously given their long half-life. SUMMARY: Further
      investigation is necessary to explore therapies for low BMD in anorexia nervosa.
      Weight gain is to be encouraged. Transdermal estrogen in adolescents, and
      bisphosphonates in adults, have a potential therapeutic role.

PMID- 21897221
TI  - Mechanisms and treatment of hypercalcemia of malignancy.
AB  - PURPOSE OF REVIEW: Hypercalcemia of malignancy is a common paraneoplastic
      syndrome and a frequent complication of advanced breast and lung cancer, and
      multiple myeloma. The development of this malignancy complication often purports
      a poor prognosis. Thorough evaluation to establish the cause of hypercalcemia is
      essential because some patients may actually have undiagnosed primary
      hyperparathyroidism. RECENT FINDINGS: Production of humoral factors by the
      primary tumor, collectively known as humoral hypercalcemia of malignancy (HHM),
      is the mechanism responsible for 80% of cases. The vast majority of HHM is caused
      by tumor-produced parathyroid hormone-related protein followed by infrequent
      tumor production of 1,25-dihydroxyvitamin D and parathyroid hormone. The
      remaining 20% of cases are caused by bone metastasis with consequent bone
      osteolysis and release of skeletal calcium. Key therapies are saline hydration to
      promote calciuresis and bisphosphonates to reduce pathologic osteoclastic bone
      resorption. Calcitonin and glucocorticoids, especially in 1,25-dihydroxyvitamin D
      mediated HHM, also have calcium-lowering effects. SUMMARY: Recent discoveries on
      mechanisms of malignancy-associated hypercalcemia highlight the critical role of
      the osteoclast. Bisphosphonates and other novel therapies being evaluated in
      clinical trial target this bone-resorbing cell type and provide effective and
      durable serum calcium reduction.

PMID- 21897222
TI  - Role of wingless tail signaling pathway in osteoporosis:  an update of current
      knowledge.
AB  - PURPOSE OF REVIEW: Wingless tail (Wnt) pathway is crucial for osteoblast
      activation and action. This review summarizes the evidence published during the
      previous year on the emerging role of Wnt signaling alterations in the
      pathogenesis, diagnosis, and potential therapeutic approaches of osteoporosis.
      RECENT FINDINGS: New insights into the mechanisms regulating Wnt/beta-catenin
      canonical pathway, including the role of Kremen-2 receptor, lamin A/C protein,
      periostin, and pleiotropin in bone physiology, the crosstalk between the RUNX-2
      transcription-factor cascade and the Wnt pathway, and the concept that individual
      Wnt ligands may have a unique and distinct mission in bone milieu, are presented.
      Nutritional habits may affect Wnt signaling in bone. Serum sclerostin and
      dickkopf-1 levels may serve as markers of bone metabolism and disease, although
      further standardization methods are required. Finally, the effect of current
      antiosteoporotic treatments on Wnt signaling is discussed, as well as the
      therapeutic potential of drugs targeting either Wnt signaling amplification or
      Wnt antagonists' attenuation. SUMMARY: Although Wnt pathway is currently a field
      of thorough investigation, it is still far from been fully elucidated.
      Understanding its complex pathophysiology has evoked promising therapeutic
      approaches for osteoporosis. However, given that Wnt signaling is crucial for
      many tissues, emerging knowledge should be cautiously translated in therapeutics.

PMID- 21897223
TI  - Gastric secretion.
AB  - PURPOSE OF REVIEW: The review summarizes the past year's literature regarding the
      regulation of gastric exocrine and endocrine secretion, both basic science and
      clinical. RECENT FINDINGS: Gastric acid secretion is an elaborate and dynamic
      process that is regulated by neural (efferent and afferent), hormonal (e.g.
      gastrin), and paracrine (e.g. histamine, ghrelin, somatostatin) pathways as well
      as mechanical (e.g. distension) and chemical (e.g. amino acids) stimuli.
      Secretion of hydrochloric acid (HCl) by parietal cells involves translocation of
      HK-ATPase-containing cytoplasmic tubulovesicles to the apical membrane with
      subsequent electroneutral transport of hydronium ions in exchange for potassium.
      The main apical potassium channel is KCNQ1 which, when activated, assembles with
      its beta-subunit KCNE2 to function as a constitutively open, voltage-insensitive,
      and acid-resistant luminal potassium channel. Proton pump inhibitors block acid
      secretion by covalently binding to cysteine residues accessible from the luminal
      surface of the HK-ATPase. Potassium-competitive ATPase blockers (P-CABs) act by
      competing for K on the luminal surface of HK-ATPase. As they are acid-stable and
      do not require acid-dependent activation, P-CABs hold promise for rapid and
      prolonged inhibition of acid secretion. SUMMARY: We continue to make progress in
      our understanding of the physiologic regulation of gastric acid secretion. A
      better understanding of the pathways and mechanisms regulating acid secretion
      should lead to improved management of patients with acid-induced disorders.

PMID- 21897224
TI  - Probiotics and immune health.
AB  - PURPOSE OF REVIEW: The beneficial effects of probiotics have been demonstrated in
      many diseases. One of the major mechanisms of probiotic action is through the
      regulation of host immune response. This review highlights the recent scientific
      research findings that advance our understanding of probiotic regulation of the
      host immune response with potential application for disease prevention and
      treatment. RECENT FINDINGS: Probiotic genomic and proteomic studies have
      identified several genes and specific compounds derived from probiotics, which
      mediate immunoregulatory effects. Studies regarding the biological consequences
      of probiotics in host immunity suggested that they regulate the functions of
      systemic and mucosal immune cells and intestinal epithelial cells. Thus,
      probiotics showed therapeutic potential for diseases, including several immune
      response-related diseases, such as allergy, eczema, viral infection, and
      potentiating vaccination responses. SUMMARY: Probiotics may provide novel
      approaches for both disease prevention and treatment. However, the results of
      clinical studies regarding probiotic application are preliminary and require
      further confirmation.

PMID- 21897225
TI  - Gastrointestinal defense mechanisms.
AB  - PURPOSE OF REVIEW: We have highlighted the recent findings relating to
      gastroduodenal mucosal defense, including elements that may contribute to the
      failure of defense systems and factors that enhance mucosal healing, focusing on
      findings that elucidate new pathophysiological mechanisms. RECENT FINDINGS:
      Bicarbonate secretion is mediated by multiple types of prostaglandin E synthases,
      including membrane-bound prostaglandin E synthase-1. Mucins, growth factors, and
      trefoil factors are involved in accelerating gastric injury healing through
      epithelial reconstruction. A combination of NSAIDs and bile induce greater damage
      on the mucosa than if the two agents were acting alone. Proton pump inhibitors
      defend the mucosa from injury by promoting cellular restitution as well as
      inhibiting gastric acid secretion and reactive oxygen species (ROS) damage.
      Roxatidine, a novel H2 receptor antagonist, acts through a mechanism that
      involves nitric oxide. Melatonin enhances angiogenesis through the upregulation
      of plasma levels of gastrin and matrix metalloproteinase expression. The mucosal
      protective drug polaprezinc exhibits ROS-quenching activities.
      Lipopolysaccharides induce oxidative stress mediated by p38 mitogen-activated
      protein kinase (p38 MAPK). Aging weakens gastroduodenal mucosal defense
      mechanisms. SUMMARY: There is a wide array of pathways leading to gastroduodenal
      mucosal injury in addition to protective defense mechanisms that counteract them
      to maintain homeostasis. Increased understanding of these systems may help
      identify novel molecular targets for the prevention and treatment of mucosal
      injury.

PMID- 21897227
TI  - Prevention and treatment of acute myeloid leukemia relapse after allogeneic stem
      cell transplantation.
AB  - PURPOSE OF REVIEW: Relapse remains a major cause of treatment failure for acute
      myeloid leukemia (AML) patients treated with allogeneic hematopoietic stem cell
      transplantation (allo-HCT). Most patients that recur will perish due to low
      treatment efficacy, toxicity, or frailty issues. This review summarizes recent
      developments in clinical research and therapeutic applications for prevention and
      treatment of this complication of transplantation. RECENT FINDINGS: Several
      groups have demonstrated that monitoring minimal residual disease (MRD) after
      allo-HCT is feasible and is predictive of impending hematologic recurrence. The
      introduction of novel antileukemia agents in the preparative regimen, maintenance
      of remission treatment posttransplant, and early MRD-based therapeutic
      interventions all have the potential to improve outcomes. SUMMARY: Innovative
      basic and clinical investigation is urgently needed to improve treatment and
      prevention of AML recurrence after allogeneic transplantation.

PMID- 21897226
TI  - Update on clinical and immunological features of eosinophilic gastrointestinal
      diseases.
AB  - PURPOSE OF REVIEW: Eosinophilic gastrointestinal diseases (EGIDs) are an
      increasingly common heterogeneous group of intestinal diseases. The purpose of
      this review is to present the latest developments in the care of patients with
      EGIDs and to summarize a growing literature defining the clinical features and
      mechanistic elements of eosinophils and their complex relationships with the
      gastrointestinal tract. RECENT FINDINGS: Recent studies continue to define what
      constitutes 'normal' and 'abnormal' numbers of eosinophils in the different
      sections of the gastrointestinal tract. Symptom complexes of EGIDs appear to be
      related primarily to the mucosal, as opposed to the muscular or serosal, forms of
      EGIDs. Dissection of the mucosal microenvironment is uncovering a complex array
      of cells, other than eosinophils, that likely contribute to the inflammatory
      response associated with EGIDs. Mechanistic studies have identified genetic
      perturbations (eotaxin-3, thymic stromal lymphopoietin, IL-13, and filaggrin)
      that may also contribute to the development of the most often encountered and
      well studied EGID, eosinophilic esophagitis. SUMMARY: Clinicians should remain
      aware of EGIDs as a diagnostic possibility for patients with common
      gastrointestinal symptoms. Additional research is needed to determine mechanistic
      processes leading to dysfunction associated with eosinophilic gastrointestinal
      inflammation.

PMID- 21897228
TI  - Future of hepatitis C therapy:  development of direct-acting antivirals.
AB  - PURPOSE OF REVIEW: The landscape of hepatitis C virus (HCV) therapy will change
      considerably over the next decade with the probable licensure of many HCV direct
      acting antiviral (DAA) therapy agents. This review will outline the data on the
      initial two DAA agents licensed (protease inhibitors telaprevir and boceprevir)
      and cover potential future therapeutic strategies and challenges for DAA-based
      therapy, including in the context of HIV/HCV coinfection. RECENT FINDINGS: Phase
      III trials evaluating the addition of telaprevir or boceprevir to pegylated
      interferon and ribavirin in both HCV treatment naive and experienced populations
      with chronic HCV genotype 1 have demonstrated considerable improvements in
      sustained virological response, with many patients able to shorten total
      treatment duration from 48 to 24-36 weeks. Although these initial DAA-based
      treatment results are encouraging, additional toxicity, problematic dosing
      schedules, and potential drug-drug interactions pose challenges for clinical
      management, particularly in HIV/HCV coinfection. Phase II trials with telaprevir
      and boceprevir in HIV/HCV populations are underway. Subsequent DAA agents appear
      to have improved tolerability and dosing schedules and open the door for
      interferon (IFN)-free DAA-based combination therapy. SUMMARY: Development of DAA
      therapy will lead to a major shift in HCV clinical management, particularly with
      the potential for IFN-free combination therapy.

PMID- 21897230
TI  - Statins and the risk of new-onset diabetes:  a review of recent evidence.
AB  - PURPOSE OF REVIEW: Statins are the most prescribed medications worldwide with a
      proven ability to reduce major cardiovascular events. Recent data have revealed
      that statin therapy is associated with an increased risk for developing diabetes.
      We discuss the relevant data including newly published results, which demonstrate
      a dose-dependent association, we place these findings in clinical context and we
      consider clinical implications. RECENT FINDINGS: A recent meta-analysis of most
      major placebo and standard care-controlled statin trials with more than 90,000
      participants confirmed that statin therapy was associated with a 9% increased
      risk of developing diabetes. Newly published data have confirmed a dose-dependent
      effect, with 12% higher risk of developing diabetes on intensive-dose statin
      therapy compared with moderate-dose therapy. In this meta-analysis, one
      additional patient developed diabetes for every three patients protected from a
      major cardiovascular event. The observation of higher diabetes risk remains
      unexplained at present, although studies in animal models suggest the possibility
      of impaired peripheral insulin signalling induced by statin therapy. SUMMARY: The
      cardiovascular benefits of statin therapy clearly outweigh the risk of developing
      diabetes. However, the data suggest the need to make patients aware of this
      possible risk and to monitor patients for development of diabetes, especially on
      intensive-dose therapy.

PMID- 21897229
TI  - The cardioprotective effects of metformin.
AB  - PURPOSE OF REVIEW: In patients with type 2 diabetes mellitus, treatment with
      metformin is associated with a lower cardiovascular morbidity and mortality,
      compared with alternative glucose-lowering drugs. It has been suggested that
      metformin might exert direct protective effects on the heart. RECENT FINDINGS:
      This review appraises recent experimental animal studies on the effect of
      metformin on myocardial ischaemia-reperfusion injury and remodeling. In murine
      models of myocardial infarction, the administration of metformin potently limits
      infarct size. Activation of adenosine monophosphate-activated protein kinase,
      increased formation of adenosine, and the prevention of opening of the
      mitochondrial permeability transition pore at reperfusion all contribute to this
      cardioprotective effect. In addition, metformin therapy attenuates postinfarction
      cardiac remodeling. There is evidence that activation of adenosine monophosphate
      activated protein kinase and endothelial nitric oxide synthase, and a reduced
      collagen expression are crucial for this effect. SUMMARY: The finding that
      metformin limits myocardial infarct size and remodeling in animal models of
      myocardial infarction suggests that patients suffering from myocardial ischaemia
      could benefit from treatment with metformin, even when these patients do not have
      diabetes. Currently, several clinical trials are being performed to test this
      hypothesis.

PMID- 21897231
TI  - Achieving the goal:  results from the Fistula First Breakthrough Initiative.
AB  - PURPOSE OF REVIEW: This review summarizes the background and implementation of
      the Fistula First Breakthrough Initiative (FFBI), published information about
      changes in vascular access practice since its inception, and several issues
      raised by the program. RECENT FINDINGS: The FFBI is a surveillance system using
      the End-Stage Renal Disease (ESRD) Networks to spread improvement ideas.
      Concomitant with implementation of the program, prevalent arteriovenous fistula
      use has increased an average of 3.3% annually since 2003, an incremental
      improvement of 1.3% over the preexisting trend. At the same time, long-term
      central venous catheter (CVC) use declined among the prevalent population.
      Increasingly, individual facilities are achieving the FFBI goal of 66% prevalent
      arteriovenous fistula use; however, results vary across geographic regions and
      are not explained by patient demographic and clinical characteristics alone.
      SUMMARY: ESRD Network interventions as a function of the FFBI are associated with
      increasing arteriovenous fistula use and likely contributed to improvement, but
      improvement cannot be unequivocally attributed to the Networks due to lack of
      rigorous research design. Questions and opportunities remain. It is not yet clear
      how to identify patients who may not be appropriate candidates for an
      arteriovenous fistula. The ultimate impact of the FFBI on patient mortality is
      yet to be determined. The FFBI must continue to identify variations in use and
      the contributing causes, and implement strategies to address these causes if the
      FFBI goal is to be fully achieved.

PMID- 21897232
TI  - Toxic neuropathy.
AB  - PURPOSE OF REVIEW: The aim is to review the recent publications highlighting
      current areas of research on the subject of toxic and drug-related neuropathies.
      RECENT FINDINGS: The emphasis in chemotherapy-induced peripheral neuropathy is on
      trying to elucidate underlying mechanisms using neurophysiological techniques,
      such as excitability studies. These data are also being used to identify the
      earliest presymptomatic changes. A large number of papers have been published on
      chemoprotectants, both in animal models and patients. According to the Cochrane
      criteria, none of the clinical trials have been shown to be effective.
      Pharmacogenetic techniques used on tumour and host tissue are now in the
      embryonic stages of trying to identify genes which may help in predicting
      individuals at high risk of developing drug-induced neuropathies. A review of
      alcohol-induced neuropathy provides evidence to suggest reclassification from a
      nutritional to a toxic neuropathy. Nitrous oxide, which causes myeloneuropathy,
      is increasingly used as a recreational drug. A red flag has been raised with the
      triazole antifungal agents, itraconazole and voriconazole, causing neuropathy.
      SUMMARY: The introduction of new neurophysiological techniques, such as
      excitability studies and pharmacogenetics, holds promise in elucidating the
      underlying mechanisms of drug-induced neuropathies. Furthermore, they will help
      identify the patients at highest risk of developing drug-induced neuropathies.
      The hope still remains of identifying chemoprotective agents - the results of
      animal and human studies suggest there are reasons to be optimistic. Clinicians
      need to aware of nitrous oxide myeloneuropathy and triazole-induced neuropathy.

PMID- 21897233
TI  - Ovarian aging:  latest thoughts on assessment and management.
AB  - PURPOSE OF REVIEW: In the past few decades, women have been intentionally
      delaying pregnancy and ovarian aging has become one of the most detrimental
      factors of pregnancy achievement. This review will discuss contemporary methods
      of ovarian aging assessment and present an overview of current management
      strategies. RECENT FINDINGS: Antimullerian hormone (AMH) and antral follicle
      count (AFC) seem to be the most reliable predictors of ovarian aging appraisal.
      Nevertheless, they have not been shown to predict pregnancy achievement in
      assisted reproduction. Heritability has a high impact on ovarian aging. Employing
      several genetic approaches, it is now being widely investigated, but the task is
      far from being accomplished. Although multivariate models have not been proven to
      be superior to AFC, new data support the notion that chronological age and
      genetic markers inclusion may increase their reliability. Several strategies have
      been suggested to treat ovarian aging in assisted reproductive technology (ART)
      settings. None of the stimulation protocol manipulations have been found to be
      advantageous and individualization of treatment is still recommended. Ovarian
      priming by different androgen preparations has been shown to be promising but
      more randomized controlled trials are needed to support these findings. Except
      for oocyte donation other ART strategies have not shown a convincing benefit for
      ovarian aging. The new development of oocyte vitrification may well introduce
      opportunities for fertility preservation to women at risk of ovarian aging.
      SUMMARY: Proper assessment and detection of ovarian aging, employing current or
      developing predictors of ovarian reserve, especially genetic tests, may enable
      health providers to recommend, at appropriate biological time, early pregnancy
      achievement or fertility preservation in women at risk.

PMID- 21897234
TI  - Nocturia: current status and future perspectives.
AB  - PURPOSE OF REVIEW: Nocturia is a bothersome and highly prevalent condition
      characterized by the need to wake to void at night. Nocturia is equally common in
      men and women, and although its prevalence increases with age, a significant
      proportion of younger people are also affected. Nocturia leads to fragmentation
      of sleep and consequently to a serious decline in daytime functioning and in
      quality of life and health. Its impact should not be underestimated by clinicians
      and therefore a review on nocturia is timely and relevant. RECENT FINDINGS:
      Traditionally, nocturia is regarded as a symptom of benign prostatic enlargement
      and/or overactive bladder syndrome, with treatment therefore directed toward
      increasing the capacity of the bladder to hold urine. Such treatments have proven
      ineffective in many patients because nocturnal polyuria, an overproduction of
      urine at night, has been found to be present in the majority of patients.
      Nocturia can be attributed to some underlying pathological factors but it can
      also be a distinct clinical entity with specific pathogenesis. Frequency-volume
      charts are recommended for routine use in clinical practice, to determine whether
      nocturia is a result of excessive urine production at night, or of small voided
      volumes due to bladder problems, or a combination of these factors. Desmopressin,
      a synthetic analogue of the antidiuretic hormone, should be considered in
      patients with nocturia where nocturnal polyuria is present. SUMMARY: Contrary to
      popular and medical misconception nocturia is an important condition leading to
      general morbidity and with serious impact on overall quality of life and health.
      We advise clinicians to pay attention to nocturia and diagnostics should be
      offered. Treatment modalities are available and have to be discussed with the
      patient.

PMID- 21897235
TI  - Chlamydia trachomatis screening in young women.
AB  - PURPOSE OF REVIEW: As the number of chlamydia screening programmes implemented
      worldwide increases, we summarize current understanding of the epidemiology,
      natural history, and management of chlamydia, focusing on screening in young
      women. RECENT FINDINGS: Chlamydia diagnoses continue to rise, with young women at
      high risk. Recently published trials show that the risk of serious reproductive
      health outcomes is lower than previously thought. They illustrate that
      significant barriers - both practical and cultural - remain to engaging young
      people and health professionals in routine testing for sexually transmitted
      infections. Chlamydia control efforts have driven innovative approaches to
      testing including new approaches to engaging young people in discussions of
      sexual health and screening accessed via the Internet. SUMMARY: Chlamydia is
      highly prevalent among young women and may cause serious reproductive sequelae.
      Gaps in our knowledge of the epidemiology, natural history and immunology of this
      organism continue to hamper efforts to control it. Sexual health promotion and
      screening of young people remain the mainstay of population control, although
      there is as yet no strong evidence of health screening benefits. Control efforts
      will require new strategies to engage young people and health professionals to
      normalize sexual health testing.

PMID- 21897236
TI  - Genital trauma in prepubertal girls and adolescents.
AB  - PURPOSE OF REVIEW: To look critically at recent research articles that pertain to
      children and adolescents who present with genital injuries. RECENT FINDINGS:
      Emerging evidence supports links to long-term psychological sequelae of child
      sexual abuse. Parents should be educated to instruct their children regarding
      types of child abuse and prevention. 'Medicalization' of female genital
      mutilation (FGM) by health providers, including 'cutting or pricking', is
      condemned by international organizations. SUMMARY: Genital injuries whether
      accidental or intentional need to be reported with standardized terminology to
      allow for comparisons between reported outcomes. Motor vehicle accidents
      associated with pelvic fractures may result in bladder or urethral trauma.
      Adverse long-term psychosocial behaviors may be sequelae of child sexual abuse.
      FGM is willful damage to healthy organs for nontherapeutic reasons, and a form of
      violence against girls and women. Healthcare providers should counsel women
      suffering from the consequences of FGM, advise them to seek care, counsel them to
      resist reinfibulation, and prevent this procedure from being performed on their
      daughters.

PMID- 21897237
TI  - A review of the use of psychotropic medication in pregnancy.
AB  - PURPOSE OF REVIEW: There is increasing awareness within obstetric services of the
      importance of treating maternal mental illness due to the association with
      increased maternal mortality, morbidity and poorer child outcomes. However, there
      is limited research on the risks and benefits of pharmacological treatment of
      women in pregnancy. This review is focused on studies published in the past 18
      months. RECENT FINDINGS: Antidepressants and antiepileptic mood stabilizers are
      the most frequently studied of the pharmacological treatments for mental illness.
      There are clear risks of neonatal serotonin discontinuation symptoms associated
      with antenatal antidepressant use. It remains unclear whether there is an
      elevated risk of malformations, persistent pulmonary hypertension of the newborn,
      prematurity, low birth weight and negative child developmental outcomes. Mood
      stabilizers have been associated with an increased malformation risk and some are
      associated with poorer neonatal and child developmental outcomes. There are
      available only limited studies on antipsychotics in pregnancy. SUMMARY: Given the
      limited research on psychotropic medication in pregnancy, each woman, in
      collaboration with her clinician, needs to consider the risks in the context of
      her individual circumstances. However, any consideration of the risks of
      pharmacological treatment must be considered in relation to the risks associated
      with untreated mental illness.

PMID- 21897238
TI  - Review of Susac syndrome.
AB  - PURPOSE OF REVIEW: The quest to better understand Susac syndrome has led to
      advancements in different aspects of the disease. The present article reviews the
      current literature on the clinical presentation, diagnostic modalities and trends
      in the management of Susac syndrome. RECENT FINDINGS: The pathogenesis of Susac
      syndrome still remains unclear. Fluorescein angiography demonstrates arterial
      wall hyperfluorescence of the arterioles at various locations along the course of
      the vessels suggesting a primary endotheliopathy. Multifocal electroretinogram
      (mfERG) provides evidence of focal retinal dysfunction related to branch retinal
      artery occlusion (BRAO). Diffusion tensor imaging demonstrates widespread
      disruption in the normal appearing white matter with damage to the genu of the
      corpus callosum considered relatively specific for Susac syndrome. Single photon
      emission computerized tomography imaging failed to identify perfusion
      abnormalities with 99mTc-ethyl cysteinate dimer in a patient with Susac syndrome.
      SUMMARY: Susac syndrome is a multisystemic microvascular occlusive
      endotheliopathy with suspected immune-mediated pathogenesis. The incidence may be
      more common than previously thought. Diagnosing Susac syndrome can be
      challenging, especially in patients presenting without all features of the
      clinical triad of encephalopathy, BRAO and hearing loss. Awareness of the
      condition, a high index of suspicion in any patient with unexplained
      encephalopathy, a dilated fundus examination, audiogram and typical MRI findings
      aid in the prompt diagnosis of the condition. Successful treatment has been
      documented with various immunosuppressive treatment regimens.

PMID- 21897239
TI  - Ocular Behcet disease:  current therapeutic approaches.
AB  - PURPOSE OF REVIEW: To alert physician to timely recognition and current treatment
      of recurrent hypopyon iridocyclitis or panuveitis in ocular Behcet disease (OBD).
      RECENT FINDINGS: Interferon-alpha, rituximab, intravitreal triamcinolone, and
      biological response modifiers by tumor necrosis factor inhibitors such as
      infliximab and adalimumab are being used increasingly for the treatment of severe
      sight-threatening ocular inflammation including retinal vasculitis and cystoid
      macular edema (CME). SUMMARY: Biological agents offer tremendous potential in the
      treatment of OBD. Given that OBD predominantly afflicts the younger adults in
      their most productive years, dermatologist, rheumatologist, internist, or general
      practitioners supervising patients with oculo-articulo-oromucocutaneous syndromes
      should be aware of systemic Behcet disease. Early recognition of ocular
      involvement is important and such patients should strongly be instructed to visit
      immediately an ophthalmologist, as uveitis management differs from extraocular
      involvements with high ocular morbidity from sight-threatening complications due
      to relapsing inflammatory attacks in the posterior segment of the eye. A single
      infliximab infusion should be considered for the control of acute panuveitis,
      whereas repeated long-term infliximab infusions were proved to be more effective
      in reducing the number of episodes in refractory uveoretinitis with faster
      regression and complete remission of CME.

PMID- 21897240
TI  - Effects of smoking on ocular health.
AB  - PURPOSE OF REVIEW: To review recent data on the effects of smoking on ocular
      health. RECENT FINDINGS: Smoking has been associated with a myriad of negative
      ocular health effects including age-related macular degeneration (ARMD) and
      cataract. Most recently, several papers have demonstrated a connection between
      smoking and ocular inflammation. Smokers are both more likely to develop ocular
      inflammation and to have more severe disease as manifested by poorer presenting
      vision and a higher risk of recurrent disease compared to nonsmokers. Smoking has
      also been shown to enhance the effect of genetic susceptibility with regards to
      the presence and development of ARMD. Finally, the negative effects of smoking on
      ocular disease have been increasingly documented in nonwhite populations outside
      of the USA. However, despite the abundance of data, public awareness on the
      adverse consequences of smoking on vision is lacking in the USA. In contrast,
      Australia improved public knowledge by launching a successful antitobacco health
      campaign highlighting the effects of smoking on ocular health. SUMMARY: These
      findings suggest that eye care professionals should discuss and offer options for
      smoking cessation as part of the management of patients with ocular diseases,
      especially in those with ocular inflammation, ARMD, lens opacities/cataract, and
      thyroid-associated orbitopathy. Health campaigns using existing medical data can
      improve public awareness on the connection between tobacco and visual impairment.

PMID- 21897241
TI  - Sarcoidosis.
AB  - PURPOSE OF REVIEW: Sarcoidosis is a multisystem disorder that can include ocular
      lesions. Although the precise etiology of the disease is as yet not well known,
      it is gradually becoming clearer as a result of much intensive research. The
      scope of this review is to evaluate the current understanding of sarcoidosis,
      specifically the pathogenesis of the disease and the therapeutic possibilities.
      RECENT FINDINGS: Inherited factors for this disease are gradually being
      identified by many large-scale genetic studies. As for treatment, biological
      drugs against inflammatory cytokines, such as tumor necrosis factor-alpha, are
      beginning to be used in sarcoidosis patients. SUMMARY: The exact etiology of
      sarcoidosis is still unknown. Further genetic studies in various ethnic
      populations are required to gain a better understanding of the pathogenesis of
      sarcoidosis. The data of clinical trials of biological drugs are accumulating,
      and it is necessary to produce a guideline for the use of these drugs on the
      basis of the benefits and risks to the patient.

PMID- 21897242
TI  - Review and update of intraocular therapy in noninfectious uveitis.
AB  - PURPOSE OF REVIEW: To review new clinically relevant data regarding the
      intraocular treatment of noninfectious uveitis. RECENT FINDINGS: Triamcinolone
      acetonide, the most commonly used intravitreal corticosteroid for treatment of
      uveitis and uveitic macular oedema has a limited duration of action and is
      associated with a high risk of corticosteroid-induced intraocular pressure (IOP)
      rise and cataract. Recent advances have led to the development of sustained
      release corticosteroid devices using different corticosteroids such as
      dexamethasone and fluocinolone acetonide. Treatment options for patients who have
      previously exhibited corticosteroid hypertensive response have also expanded
      through the use of new noncorticosteroid intravitreal therapeutics such as
      methotrexate and antivascular endothelial growth factor (anti-VEGF) agents.
      SUMMARY: Ozurdex dexamethasone implant appears to have a better safety profile,
      and a slightly long-lasting effect than triamcinolone acetonide. The Retisert
      implant allows the release of corticosteroids at a constant rate for 2.5 years,
      but it requires surgical placement and its use is associated with a very high
      risk of cataract and requirement for IOP-lowering surgery. For patients who are
      steroid responders, methotrexate may offer a better alternative to corticosteroid
      treatment than anti-VEGF agents, but controlled trials are required to confirm
      this.

PMID- 21897243
TI  - Bridges to lung transplantation.
AB  - PURPOSE OF REVIEW: Bridging to lung transplantation remains a controversy.
      Individually, it may be a life-saving therapy to use ventilation and
      extracorporeal means for gas exchange to keep a patient alive until lung
      transplantation. Collectively, this may lead to a selection of patients with the
      worst outcome. New technologies have become available to minimize the adverse
      events of extracorporeal devices. This may have an impact on the indication and
      use of such devices and also on the outcome. RECENT FINDINGS: Literature of the
      last 3 years were reviewed for new aspects of extracorporeal gas exchange
      (extracorporeal membrane oxygenation, ECMO) in order to define the status quo of
      these therapeutic tools in bridging to lung transplantation. It was found that
      new oxygenator technologies as well as pump designs miniaturized ECMO systems. In
      addition, a variety of possibilities for specific indications were described.
      Recently, many programs work on concepts to use ECMO no longer in addition to
      mechanical ventilation, but to avoid or wean from ventilation. This situation
      represents a paradigm shift in the bridging strategies for lung transplantation.
      SUMMARY: Bridging to lung transplantation changes to concepts avoiding the
      sequels mechanical ventilation and thereby offers improvement of lung recipients
      prior to the transplant procedure.

PMID- 21897244
TI  - Donation after cardiac death lung transplantation outcomes.
AB  - PURPOSE OF REVIEW: Lung transplantation is now a well established treatment
      option for several end-stage respiratory diseases. Survival after lung
      transplantation has significantly improved over the last decade. The primary
      limitation to increased utilization of lung transplantation remains donor
      scarcity. Suitable allografts have been procured from donors after determination
      of neurologic death and from donors after determination of cardiac death (DDCD or
      DCD). Historically, the first human lung transplantation performed, utilized an
      allograft procured after cardiovascular death, also referred to as nonheart
      beating donor.The experience at University of Wisconsin in 1993 reintroduced DCD
      lung transplantation with the first successful clinical case. RECENT FINDINGS: A
      potential additional lung allograft source, DCD lung transplantation has been
      established with very acceptable outcomes observed by several centers. We provide
      the relevant background for the rationale of donor allograft expansion to include
      DCD lungs from controlled (Maastricht category III donors). SUMMARY: This review
      considers the available evidence for DCD lung transplantation and compares
      reported primary graft dysfunction rates and current survival data available.

PMID- 21897245
TI  - Auxiliary liver transplantation in children.
AB  - PURPOSE OF REVIEW: Auxiliary liver transplantation (ALT) has developed as a
      technique for treating patients with acute liver failure. The surgical techniques
      of ALT have been refined and current patient survival appears to be similar to
      that observed with conventional liver replacement for acute liver failure. RECENT
      FINDINGS: Our understanding of liver regeneration has improved with experience
      and it is possible to identify patient and disease groups that are more likely to
      regenerate and wean off immunosuppression after ALT. Withdrawal of
      immunosuppression is possible in at least two thirds of survivors up to 4 years
      post transplant. Young patients have most to gain in the long term from
      immunosuppression withdrawal. Documentation of liver regeneration should be
      performed by liver histology, nuclear medicine scanning and CT volumetry. Weaning
      should be gradual to allow for graft atrophy to avoid complications. ALT has also
      been utilised for the management of inborn errors of metabolism based in the
      liver and for other rare problems and these will be briefly addressed in the
      review. SUMMARY: Auxiliary liver transplantation should be considered for the
      treatment of children with acute liver failure satisfying current criteria for
      liver transplantation.

PMID- 21897246
TI  - Predictors of long-term outcome after liver transplant.
AB  - Liver transplantation is the standard of care for children with life-threatening
      liver disease. Survival rates posttransplantation are rising with current 1-year
      and 5-year rates being greater than 90% and 85%, respectively. Numerous factors
      contribute to posttransplant outcomes of graft and patient survival, including
      improved surgical techniques, immunosuppressive regimens, and posttransplant
      management. The present review aims to discuss predictors of long-term outcomes
      of pediatric transplant recipients and identify potential risk factors.

PMID- 21897247
TI  - Emerging dilemmas with methicillin-resistant Staphylococcus aureus infections in
      children.
AB  - PURPOSE OF REVIEW: There has been an increase in the incidence of methicillin
      resistant Staphylococcus aureus (MRSA) infections in recent years. This article
      reviews the literature on three manifestations of MRSA infections in the head and
      neck of children: sinonasal infections, otologic infections, and neck abscesses.
      RECENT FINDINGS: Historically nosocomial in origin, MRSA infections more recently
      are found to occur in otherwise healthy patients with no obvious risk factors.
      This community-acquired MRSA is known to be responsible for cutaneous abscesses
      in various regions of the body. Nasal carriage in healthy children is thought to
      account for increasing incidence of infections involving the respiratory tract as
      well as deep-space neck infections. Although these community-acquired strains of
      MRSA often retain susceptibility to nonbeta lactam antibiotics, there are reports
      of clindamycin resistance. SUMMARY: There is an increase in incidence of MRSA
      among infections involving the head and neck in children. Vigilant monitoring of
      antibiotic susceptibilities is warranted as well as judicious use of culture
      directed antibiotic agents in their treatment. Topical therapy may play an
      important role in treatment of infections involving the sinonasal tract and ear.

PMID- 21897248
TI  - Nanoparticle-based delivery for the treatment of inner ear disorders.
AB  - PURPOSE OF REVIEW: The delivery of targetable synthetic vectors that can carry a
      variety of drugs, proteins, and nucleic acids, such as DNA and small interfering
      RNA (siRNA), to mammalian cells is important as a potential therapeutic system
      that avoids the problems that are associated with viruses. RECENT FINDINGS: The
      so-called multifunctional nanocarriers that are equipped with several functions,
      such as targetability, shelter from the immune system, and opsonization, and are
      capable of delivering payload across the nuclear envelope, have been synthesized.
      To improve transfection efficiency, a group of novel peptides have been attached
      to the surface of the carrier that will enhance endosomal escape and promote
      nuclear entry. The targeting of tropomyocin receptor kinase B (TrkB) with ligands
      enhances uptake in spiral ganglion cell culture. Treatment cargos have included
      growth factors such as the Math-1 gene, short hairpin RNA, and steroids. The
      problems with current synthetic nanocarriers are poorer selectivity,
      internalization, and transfection rate compared with viral vectors. SUMMARY:
      Within a few years, when the synthetic vectors have been optimized, the first
      human drugs/proteins/gene product-based therapies will become available in a
      phase I study.

PMID- 21897249
TI  - Inflammatory mechanisms in major depressive disorder.
AB  - PURPOSE OF REVIEW: As the 'monoamine hypothesis of depression' fails to explain
      all aspects of major depression, additional causes are being investigated.
      Several observations suggest that inflammatory mechanisms pay a role in the cause
      of major depressive disorder (MDD). This article reviews their role in major
      depression. RECENT FINDINGS: Recent studies support the concept that inflammatory
      mechanisms play a crucial role in the pathomechanisms of major depression. Major
      depression shares similarities with 'sickness behavior', a normal response to
      inflammatory cytokines. Elevations in proinflammatory cytokines and other
      inflammation-related proteins in major depression were found in plasma and
      cerebrospinal fluid (CSF) as well as in postmortem studies. Elevated levels of
      proinflammatory cytokines persist after clinical symptoms of depression are in
      remission and can also predict the onset of a depressive episode. Antidepressant
      treatment can lead to a normalization of elevated cytokine levels in major
      depression. Finally, we understand how inflammatory mechanisms affect the
      metabolism of tryptophan and how nonsteroidal antiinflammatory drugs (NSAIDs) can
      interfere with the effects of antidepressants. SUMMARY: Further studies are
      needed to fully understand the role of inflammatory mechanisms in major
      depression and the potential treatment implications.

PMID- 21897250
TI  - Recent developments for naturalizing the mind.
AB  - PURPOSE OF REVIEW: To examine recent philosophical work which impacts on fitting
      mental content into a satisfactory picture of nature. RECENT FINDINGS: Both
      reductionist and nonreductionist forms of naturalism about mental content have
      sustained criticism. SUMMARY: The connection between having a mind and fitting a
      rational pattern remains an important insight.

PMID- 21897251
TI  - Childhood trauma and posttraumatic stress disorder in patients with psychosis: 
      clinical challenges and emerging treatments.
AB  - PURPOSE OF REVIEW: To review the current literature on childhood trauma and
      emerging treatments for posttraumatic stress disorder (PTSD), one of its most
      prevalent consequences, in patients with psychotic disorders. RECENT FINDINGS: Of
      patients with psychosis, 40-50% report either childhood sexual abuse or childhood
      physical abuse, and 11-46% fulfil a diagnosis of PTSD. About one-third of
      patients report childhood emotional abuse in the absence of other forms of
      childhood trauma. More robust evidence is mounting to support the role of
      childhood trauma in the aetiology of psychosis, but more research is needed to
      understand the underlying mechanisms. Patients with a history of childhood trauma
      and/or PTSD have a more severe clinical profile compared with those without these
      experiences, worse overall functioning, and lower remission rates. Research
      suggests that instruments assessing childhood trauma and PTSD developed for the
      general population are also appropriate for use among people with psychosis, and
      trauma-focussed treatments can be used safely and effectively in this group.
      SUMMARY: Childhood trauma and its consequences are highly prevalent among
      patients with psychosis and severely affect the course and outcome. Treatment
      approaches appropriate for this population need to be further evaluated and
      implemented into routine practice.

PMID- 21897252
TI  - Do it yourself? Self-help and online therapy for people with obsessive-compulsive
      disorder.
AB  - PURPOSE OF REVIEW: In spite of advances in the understanding and treatment of
      obsessive-compulsive disorder (OCD), for most patients some symptoms persist even
      after therapeutic intervention. Another large subgroup does not seek treatment at
      all, particularly due to shame or fear of stigma. The treatment gap in OCD is
      large and self-help is increasingly seen as a low-threshold form of intervention
      for individuals with minor symptoms or who are currently treatment-reluctant. Our
      review summarizes the expanding but still small literature on self-help and
      Internet interventions for OCD and provides advice on how to conduct (Internet)
      studies on self-help. Strategies to deal with methodological problems that
      notoriously plague Internet research are discussed. RECENT FINDINGS: Despite
      methodological limitations inherent in most studies considered for the current
      review, as well as the unreplicated nature of some of the more recent findings,
      self-help tools hold some promise. In particular, self-help interventions that
      are rooted in evidence-based concepts may be helpful as an add-on to standard
      interventions and as (initial) therapeutic strategies for those who are presently
      reluctant to participate in face-to-face treatment. SUMMARY: The current review
      identifies self-help, which is based on evidence-based concepts, as a promising
      clinical tool for the treatment of OCD. The current literature suggests that self
      help can be a facilitator and aid to standard face-to-face interventions, rather
      than a rival.

PMID- 21897253
TI  - Narrative and psychiatry.
AB  - PURPOSE OF REVIEW: The study of narrative has become increasingly important in
      the humanities and social sciences and there is a growing use of narrative in the
      clinical domains of medicine and psychotherapy. Narrative psychiatry is also on
      the rise and promises to help psychiatry be responsive to increasing critical
      concerns from inside and outside the field. RECENT FINDINGS: The field of
      narrative is vast and cuts across a variety of disciplines. Contemporary scholars
      in narrative medicine build on 30 years of work in medical humanities and
      bioethics to rigorously understand human variables in medicine and to improve
      physician empathy. Narrative psychotherapists have developed a new model of
      psychotherapy and a meta-narrative theory of diverse mental health interventions.
      Psychiatrists have picked up these insights and are finding them invaluable for
      navigating contemporary issues in psychiatry. SUMMARY: Narrative theory has
      become important in the humanities, social sciences, medicine, and psychotherapy
      for understanding human meaning making. Increasingly, the tools of narrative are
      proving valuable for psychiatry as well. Narrative psychiatry does not negate or
      supersede other knowledge and research in psychiatry, but it can help psychiatry
      understand how people use psychiatric knowledge, among other cultural resources,
      for making sense of psychic difficulties and psychic differences.

PMID- 21897254
TI  - Nongenetic influences on cystic fibrosis outcomes.
AB  - PURPOSE OF REVIEW: Despite dramatic improvements over the last several decades,
      tremendous variation exists in cystic fibrosis (CF) health outcomes. Genetic
      explanations for variations in disease progression are a promising source of
      information regarding disease biology and pathophysiology, but an understanding
      of nongenetic factors provides more immediate tools for improving disease
      outcomes. RECENT FINDINGS: The clinical course of CF for any individual with CF
      is determined by the interaction of genetic endowment (including CFTR and
      modifier genes), the physical environment (including environmental tobacco smoke,
      outdoor pollution, and pathogenic microorganisms), the sociodemographic,
      cultural, and family context (which mediates stress, social support, and disease
      self-management skills), and variations in delivery and acceptance of healthcare
      treatments. The evidence linking socioeconomic status (SES) with CF outcomes
      continues to be strong, and appears to be primarily due to associations with
      environmental and sociocultural stressors and disease-management behaviors rather
      than barriers in access to healthcare. SUMMARY: Attempts to eliminate detrimental
      environmental exposures, improve disease self-management skills, and ensure
      consistently optimal healthcare practices will likely decrease variations in
      outcomes including SES-related disparities. Low SES is an important marker of
      adverse exposures and outcomes which are present throughout the CF population.

PMID- 21897255
TI  - Cystic fibrosis lung transplantation.
AB  - PURPOSE OF REVIEW: This review summarizes recently published investigations on
      issues pertaining to cystic fibrosis (CF) lung transplantation. We specifically
      focus on indications and candidate selection as well as infectious and
      noninfectious issues specific to CF lung transplant recipients. RECENT FINDINGS:
      Recent studies have focused on candidate adequacy in high-risk CF patients. We
      review the current literature on individuals who develop respiratory failure
      requiring mechanical ventilation and those patients with a pretransplant
      diagnosis of pulmonary hypertension. Furthermore, the management of peri
      operative infectious issues is reviewed including recurrent infections with
      multidrug-resistant bacterial, mycobacterial, and fungal organisms. Other CF
      specific issues addressed include common comorbidities such as CF-related
      diabetes, gastroesophageal reflux, CF liver disease, and bone metabolism.
      SUMMARY: Lung transplantation is a limited, but potentially life-saving
      therapeutic option for patients with CF. Optimal candidate selection and
      awareness of CF-specific issues in the pretransplant and posttransplant setting
      may lead to better long-term outcomes.

PMID- 21897257
TI  - Addressing 'the elephant on the table':  barriers to end of life care
      conversations in heart failure - a literature review and narrative synthesis.
AB  - PURPOSE OF REVIEW: Heart failure is a life-limiting illness, but with great
      uncertainty over its prognosis. Policy increasingly states the importance of
      discussions about end of life care between patients and their clinicians. This
      study reviews the extent to which there is evidence that these conversations
      occur for heart failure patients in practice. RECENT FINDINGS: Although several
      opinion pieces and guidelines on this topic have emerged in recent years, little
      new empirical data have been published. Papers publishing empirical data since
      2005 and other literature suggest that these conversations rarely occur. Many
      clinicians feel uncomfortable or lack confidence; and there is uncertainty
      whether patients want such discussions. Barriers and facilitators for discussions
      with heart failure are identified, regarding the nature of the disease, resource
      constraints and attitudes. The consequence is that disempowered patients rarely
      have such discussions: the 'elephant on the table' is rarely addressed. SUMMARY:
      The wide range of barriers identified all hinder conversations about the end of
      life with heart failure patients. Individual patient preferences for the timing
      and content of such conversations must be respected, including the wish of some
      not to have such conversations at all.

PMID- 21897256
TI  - Systemic sclerosis and the heart:  current diagnosis and management.
AB  - PURPOSE OF REVIEW: When present clinically, cardiac involvement in systemic
      sclerosis (SSc) is a major risk factor for death. It is therefore vitally
      important to understand the epidemiology, screening, diagnosis, and treatment of
      the cardiac manifestations of SSc. RECENT FINDINGS: The epidemiology of cardiac
      involvement in SSc has been the subject of several recent studies. Most
      importantly, the prevalence of overt left ventricular (LV) systolic dysfunction
      and its associated risk factors have been defined, and patients with diffuse
      cutaneous SSc appear to be most susceptible to direct cardiac involvement. From a
      diagnostic and screening standpoint, tissue Doppler echocardiography and
      natriuretic peptides have provided fresh insight into subclinical cardiac
      dysfunction in SSc. Newer techniques, such as speckle-tracking echocardiography,
      diffuse myocardial fibrosis imaging, and absolute myocardial perfusion imaging,
      are poised to further advance our knowledge. Lastly, there is now consistent
      observational data to suggest a central role for calcium channel blockers in the
      treatment of microvascular ischemia and prevention of overt LV systolic
      dysfunction, although randomized controlled trials are lacking. SUMMARY: Recent
      studies have improved our understanding of cardiac involvement in SSc.
      Nevertheless, key questions regarding screening, diagnosis, and treatment remain.
      Novel diagnostic techniques and multicenter studies should yield important new
      data, which will hopefully ultimately result in improved outcomes.

PMID- 21897258
TI  - Metabolic syndrome and sexual dysfunction.
AB  - PURPOSE OF REVIEW: To define the link between metabolic syndrome (MetS) and
      sexual dysfunction. The global epidemic of obesity and diabetes has led to a
      striking increase in the number of people afflicted with the MetS. The MetS
      consists of a myriad of abnormalities, including central obesity, glucose
      intolerance, dyslipidemia, and hypertension. RECENT FINDINGS: Although interest
      in the MetS initially arose due to its association with cardiovascular disease,
      subsequent data emerged pointing to a relationship with male sexual dysfunction.
      SUMMARY: Few randomized studies exist to guide treatment of sexual dysfunction
      related to MetS; rather, most studies have been observational in nature. Medical
      therapy has formed the mainstay of treatment.

PMID- 21897259
TI  - Management of urogenital trauma:  state of the art.
AB  - PURPOSE OF REVIEW: The field of urogenital trauma is undergoing constant
      improvement mainly due to better diagnostic tools, a shift toward standardized
      treatments and better trauma care. The purpose of this review is to summarize the
      most relevant studies published within the last 3 years on the subject. RECENT
      FINDINGS: Computerized tomography grading of renal trauma is an excellent
      predictor of the need for surgery and the final renal outcome in these patients,
      as most patients can be treated conservatively. Computerized tomography
      cystography has become the standard for the diagnosis of bladder rupture in which
      the indications for surgical intervention may be changing. The most common
      urethral trauma is posterior urethral injury due to pelvic fracture. The best
      results in adults and children are achieved by urethroplasty. SUMMARY: The
      diagnosis and treatment of genitourinary trauma is still evolving. The long-term
      sequels of these injuries may best be treated by urologists expert in urogenital
      reconstruction. In the future, tissue engineering may have an important place in
      the treatment of these patients.

PMID- 21897260
TI  - Ileal neobladder in women with bladder cancer:  cancer control and functional
      aspects.
AB  - PURPOSE OF REVIEW: Radical cystectomy and urinary diversion is the accepted
      standard of care for invasive bladder cancer. Although orthotopic neobladder is
      the preferred method of urinary diversion in men, less experience is available
      for women. Recent studies and reports on this subject are summarized and
      reviewed. RECENT FINDINGS: Urethra-sparing cystectomy in women and orthotopic
      urinary diversion can be performed safely in appropriately selected women with
      invasive bladder cancer. Excellent oncological outcomes can be expected with a
      minimal risk of urethral recurrence in case of negative frozen section of the
      proximal urethra. Orthotopic neobladder diversion offers excellent clinical and
      functional results, and should be the diversion of choice in most women following
      cystectomy. Female sexual dysfunction can be avoided in patients who received
      neurovascular preservation, although quality of life declined in women who had
      undergone non-nerve-sparing radical cystectomy. SUMMARY: Urethra-sparing
      cystectomy does not compromise the oncologic outcome in women with bladder
      cancer. The excellent functional outcome and voiding pattern with orthotopic
      urinary diversion argues in favor of this technique as the preferred method for
      lower urinary tract reconstruction after radical cystectomy. Nerve-sparing
      radical cystectomy preserves female sexual function and improves quality of life.

PMID- 21897261
TI  - What's new in urethroplasty?
AB  - PURPOSE OF REVIEW: This study provides an overview of current thinking about
      urethroplasty. RECENT FINDINGS: There have been a number of recent developments,
      principally to minimize the trauma of anterior urethroplasty and to address the
      posterior urethral complications of the treatment of prostate cancer. There also
      have been significant developments in the assessment of the outcome of
      urethroplasty and specifically of patient reported outcome measures. SUMMARY:
      These trends are likely to continue. There also seems to be a real possibility
      that cell culture techniques may finally produce clinically useful material for
      surgical practice.

PMID- 21897262
TI  - Comparison of the PaO2/FiO2 ratio in sternotomy vs. thoracotomy in mitral valve
      repair:  a randomised controlled trial.
AB  - OBJECTIVE: Cardiac surgery through a thoracotomy using one-lung ventilation (OLV)
      is thought to be associated with worse postoperative pulmonary gas exchange than
      sternotomy using two-lung ventilation (TLV), but this has not been confirmed yet.
      We, therefore, compared postoperative pulmonary gas exchange after mitral valve
      repair between sternotomy (group TLV) and thoracotomy (group OLV). DESIGN:
      Randomised controlled study. SETTING: University teaching hospital. PARTICIPANTS:
      Cardiac surgery patients. INTERVENTION: Sternotomy or thoracotomy was used for
      mitral valve repair. MEASUREMENTS: The ratio of arterial partial pressure of
      oxygen (PaO2) to fraction of inspired oxygen (FiO2) was compared in both groups
      before induction of anaesthesia (T0) and just before departure from the operating
      room to the ICU (T1). Fluid administration, transfusion requirements and urine
      output were checked intraoperatively. Postoperative haemoglobin (Hb), haematocrit
      (Hct) and creatinine were evaluated. Cardiopulmonary bypass (CPB) time,
      intubation time and ICU stay were also recorded. RESULTS: The PaO2/FiO2 ratio
      (mean +/- SD) at T1 was significantly lower than at T0 in both groups (326.9 +/-
      120.1 vs. 431.9 +/- 73.7 mmHg in group TLV, P < 0.001; 374.9 +/- 130.9 vs. 445.4
      +/- 73.7 mmHg in group OLV, P = 0.001), but did not differ significantly between
      the two groups. The doses of inotropes and vaopressors used were not
      significantly different between the groups. Intraoperative fluid administration,
      transfusion requirements, urine output and postoperative Hb/Hct and creatinine
      did not differ significantly between the groups. CPB time, intubation time and
      ICU stay also did not differ significantly between the groups. CONCLUSION:
      Perioperative pulmonary function following OLV via a thoracotomy was not
      significantly worse than that following TLV via a sternotomy in mitral valve
      repair. CLINICAL TRIAL REGISTRATION: Not registered.

PMID- 21897263
TI  - Comparison of video laryngoscopes with direct laryngoscopy for tracheal
      intubation:  a meta-analysis of randomised trials.
AB  - BACKGROUND: Video laryngoscopes have been introduced in recent years as an
      alternative choice to facilitate tracheal intubation. We conducted a meta
      analysis to assess their value when compared with direct laryngoscopy. METHODS:
      PubMed and EMBASE were searched up until 24 September 2010. Randomised trials
      that reported data on the comparison of video laryngoscopes with direct
      laryngoscopy for tracheal intubation were included. RESULTS: Eleven trials with a
      total of 1196 participants were identified. During tracheal intubation, video
      laryngoscopes can achieve a better view of the glottis and have a similar success
      rate [rate ratio 1.0; 95% confidence interval (CI) 0.99-1.01]. Overall, the time
      to tracheal intubation was not different between the video laryngoscopes and
      direct laryngoscopy (standardised mean difference 0.19; 95% CI -0.37-0.75).
      However, in a subgroup analysis, video laryngoscopes shortened the time taken for
      difficult intubation (standardised mean difference, -0.75; 95% CI -1.24 to 
      0.25). CONCLUSION: Video laryngoscopes are a good alternative to direct
      laryngoscopy during tracheal intubation. The advantage seems to be more prominent
      when difficult intubation is encountered.

PMID- 21897264
TI  - Efficacy of a self-learning station for basic life support refresher training in
      a hospital:  a randomized controlled trial.
AB  - BACKGROUND: Adult basic life support refresher training using voice feedback
      manikins has been shown to be feasible, but the superiority of this strategy over
      instructor-led (IL) refresher training for nurses in a hospital has not been
      studied in randomized trials. OBJECTIVES: To study if adult basic life support
      refresher training for nurses in a self-learning (SL) station using a voice
      feedback manikin is more effective than IL training. METHODS: A Resusci Anne
      Skills Station (Laerdal, Norway) was installed in a small room. A total of 235
      nurses were randomized to SL or IL training. After 1 month and after 7 months,
      the proportions of nurses achieving a mean compression depth of 38-51 mm, a mean
      compression rate of 80-120/min, incomplete release of at least 5 mm and a mean
      ventilation volume of 400-1000 ml were compared between the SL and IL groups.
      RESULTS: After 1 month, the proportion of nurses with any incomplete release of
      at least 5 mm was significantly lower in the SL group (23 of 54 nurses, 43%)
      compared with the IL group (33 of 47 nurses, 70%) (P=0.005). After 7 months, a
      lower proportion of nurses achieved a depth of 38-51 mm in the SL group (13 of 45
      nurses, 29%) compared with the IL group (25 of 45 nurses, 56%) (P=0.01). For the
      other outcome parameters, no differences between SL and IL training could be
      demonstrated. CONCLUSIONS: This randomized trial in a real-life setting showed
      that more nurses achieved adequate compression depth, 7 months after IL refresher
      training compared with training in a SL station. Further research is needed to
      improve the efficacy of this SL training strategy.

PMID- 21897265
TI  - Creatinine-based glomerular filtration rate estimation in patients with liver
      disease:  the new Chronic Kidney Disease Epidemiology Collaboration equation is
      not better.
AB  - OBJECTIVES: Limitations of serum creatinine in patients with an impaired liver
      function are well known. The commonly used modification of diet in renal disease
      (MDRD) equation has a low diagnostic performance to approximate kidney function
      in patients after liver transplantation (LT) and patients with liver cirrhosis
      (LC). The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula has
      been shown to provide a more accurate estimation of kidney function in patients
      with chronic kidney disease, but studies in patients with liver disease are
      lacking. METHODS: We evaluated the diagnostic performance of CKD-EPI in
      comparison with the re-expressed MDRD formula in patients after LT (group 1;
      n=59) and in patients suffering from LC (group 2; n=44). GFR was measured by
      99mTc-diethylenetriamine penta-acetic acid (group 1) and inulin clearance (group
      2). Bias, precision, and accuracy as compared with the measured GFR were
      determined. RESULTS: The measured mean GFR (95% confidence interval) was 52.3
      ml/min/1.73 m2 (47.7; 56.9; group 1) and 35.3 ml/min/1.73 m2 (29.12; 41.3; group
      2), respectively. In transplanted patients GFR estimation by CKD-EPI and MDRD did
      not significantly differ with respect to bias (9.7 vs. 4.3 ml/min/1.73 m2),
      precision (16.9 vs. 15.5 ml/min/1.73 m2) and accuracy (64.4 vs. 69.5% within 30%
      of 'true GFR'). In patients with LC, both formulae showed a very high bias (42.5
      vs. 40.1 ml/min/1.73 m2), a very low precision (20.7 vs. 25.7 ml/min/1.73 m2) and
      accuracy (6.8 within 30% of the measured GFR in both groups). CONCLUSION: The CKD
      EPI equation does not improve the creatinine-based GFR estimation in patients
      after LT. In patients with LC, both equations should not be applied as they
      extremely overestimate GFR.

PMID- 21897266
TI  - Predictors of intensive care unit utilization in gynecologic oncology surgery.
AB  - OBJECTIVES: The objectives of the study were to examine factors predicting
      intensive care unit (ICU) admission after surgery for gynecologic cancer and to
      determine the impact of ICU admission on survival. METHODS: This was a
      retrospective study of women undergoing laparotomy for staging and debulking of
      gynecologic cancer at an academic hospital with tertiary ICU facilities from July
      2000 through June 2003. Data on clinicopathologic factors, comorbidities,
      operative outcomes, and survival were obtained from medical records and
      institutional cancer registry. The chi analysis, Kaplan-Meier analysis, and Cox
      regression methods were used for analyses. RESULTS: Two hundred fifty-five
      patients met our inclusion criteria, 43 of whom had a postoperative admission to
      the ICU. Factors predicting ICU admission on univariate analysis included age 60
      years or older, hematocrit of 30% or less, albumin of 3.5 g/dL or less, and
      Charlson Comorbidity Index (CCI) score greater than 8; after multivariate
      analysis, CCI score of greater than 8 (hazard ratio, 2.5; confidence interval,
      1.11-5.69) and albumin of 3.5 or less (hazard ratio, 3.8; confidence interval,
      1.66-8.85) were associated with an increased risk of ICU admission. After
      adjusting for albumin and CCI score, ICU admission did not have a significant
      effect on survival. CONCLUSIONS: The ability to predict ICU admission helps in
      appropriate counseling of patients and identification of institutional resource
      utilization.

PMID- 21897267
TI  - Association of keap1 and nrf2 genetic mutations and polymorphisms with
      endometrioid endometrial adenocarcinoma survival.
AB  - OBJECTIVE: Dysregulation of Kelch-like erythroid cell-derived protein with CNC
      homology-associating protein (Keap)-nuclear factor E2-related factor 2 (Nrf2)
      homeostasis owing to oncogenic mutations or to endogenous alteration of protein
      expression levels is implicated in tumor resistance to adjuvant treatment. To
      understand the role of Keap1 and Nrf2 in endometrial cancer, we performed DNA
      sequencing of tumors and noted the relation of the DNA sequence with annotated
      clinicopathologic data. METHODS: We sequenced the Keap1 and Nrf2 genes in 105
      tumor specimens. Associations of genetic mutations and polymorphisms with the
      patients' clinicopathologic characteristics were evaluated. RESULTS: We detected
      9 patients with Keap1 mutations and 3 patients with Nrf2 mutations. No patient
      had both Keap1 and Nrf2 mutations. We found 2 single nucleotide polymorphisms
      within the coding region of Keap1 - rs1048290 (c. 1413C>G) and rs11545829 (c.
      1611C>T) that displayed high heterogeneity in our cohort. The c. 1413C>G
      polymorphism is significantly associated with progression-free survival by
      multivariate analysis (hazard ratio, 0.16; 95% confidence interval, 0.036-0.69; P
      = 0.014). The presence of Keap1 or Nrf2 mutations and c. 1611C>T are not
      associated with the clinical outcome of the patients. CONCLUSIONS: Mutations
      impairing Keap1-Nrf2 interaction are relatively common in endometrial cancer (12
      [11.4%] of 105). Keap1 single nucleotide polymorphism rs1048290 may be a novel
      independent prognostic marker for patients with endometrial cancer receiving
      adjuvant treatment. Therefore, genotyping patients for this Keap1 polymorphism
      will help identify patient subgroups more likely to benefit from standard
      adjuvant therapy.

PMID- 21897268
TI  - Immunofluorescence-detected infiltration of CD4+FOXP3+ regulatory T cells is
      relevant to the prognosis of patients with endometrial cancer.
AB  - OBJECTIVE: Host antitumor immune responses are associated with many types of
      immune cells and soluble components. In particular, CD8 cytotoxic T lymphocytes
      (CTLs) play a central role. Regulatory T cells (Tregs) have been reported to
      induce tumor immune tolerance in various cancers. In the present study, we
      evaluated lymphocytic infiltration in endometrial cancer tissue to clarify its
      relationship with clinicopathological factors and the prognosis of patients.
      METHODS: The study included 53 patients whose condition was diagnosed as
      endometrial cancer between 1994 and 2004 at Keio University hospital. Using
      formalin-fixed, paraffin-embedded specimens of the uterus, immunohistochemistry
      was performed with antihuman CD8, antihuman CD4, and antihuman FOXP3 primary
      antibodies, and the binding sites of the antibodies were visualized using
      fluorescence-conjugate secondary antibodies. CD4FOXP3 cells were identified as
      Tregs in this study. The numbers of CD8 cells, CD4 cells, and Tregs as well as
      the Treg/CD8 and Treg/CD4 ratios were analyzed to evaluate the relationship
      between clinicopathological factors and patient prognosis. RESULTS: Of the 53
      patients studied, 50.9% of them had early-stage disease, 49.1% had advanced stage
      disease, 47.2% had well-differentiated cancer (grade [G] 1), 24.5% had moderately
      differentiated cancer (G2), and 28.3% had poorly differentiated cancer (G3). The
      CD8 and CD4 cell counts, Treg count, and Treg/CD8 and Treg/CD4 ratios were
      significantly higher in the patients with advanced poorly differentiated
      carcinomas and with positive lymphovascular space invasion than in those with
      early well-differentiated carcinomas and with negative lymphovascular space
      invasion. In disease-free survival, the prognosis of the patients with high Treg
      counts and Treg/CD8 ratios was significantly worse than that of the patients with
      low Treg counts and Treg/CD8 ratios (P < 0.05). CONCLUSIONS: The Treg count and
      Treg/CD8 ratio may be new prognostic factors for endometrial cancer.

PMID- 21897269
TI  - Chemotherapy plus radiation in advanced-stage endometrial cancer.
AB  - HYPOTHESIS: We hypothesize that adjuvant radiation and chemotherapy improve the
      clinical benefit from treatment of advanced-stage endometrial adenocarcinoma.
      METHODS: We conducted a retrospective review of 125 patient with stage III or IVA
      endometrial adenocarcinoma who received adjuvant chemotherapy (n = 60) or
      chemoradiation (n = 65). Primary end points were rate of clinical benefit (ie,
      the percentage of patients who were alive and disease-free for at least 6 months
      after the last day of adjuvant treatment) and progression-free and overall
      survival. RESULTS: The addition of radiation to chemotherapy improved the rate of
      clinical benefit from 55% to 77%. Differences in clinical benefit were attributed
      to a reduction in the number of pelvic relapses after chemoradiation. There were
      no substantial differences in the rate of extrapelvic relapse events seen between
      the chemotherapy alone and chemoradiation groups. Patients receiving radiation
      had prolonged median progression-free survival (36 vs 17 months in chemotherapy
      alone) and median overall survival (70 vs 64 months in chemotherapy alone).
      CONCLUSIONS: The addition of radiation to chemotherapy improved the clinical
      benefit of patients with stage III or IVA endometrial adenocarcinoma. A clinical
      trial powered to evaluate clinical benefit and survival outcomes of chemotherapy
      and radiation is under way.

PMID- 21897270
TI  - Oleanen induces apoptosis of cervical cancer cells by up-regulation of Bim.
AB  - OBJECTIVE: Plants belonging to the genus Celastrus exhibit antitumor activity and
      the ability to reverse multidrug resistance in tumor cells; however, it remains
      unclear whether the compound oleanen from Celastrus hypoleucus also exhibits
      antitumor activity. The objective of this study was to explore the inhibitory
      effect of 12-oleanene-3beta, 6alpha-diol (oleanen) on the proliferation of
      cervical cancer HeLa cells in vitro, as well as its relative mechanism. METHODS:
      HeLa cells were treated with different concentrations of oleanen for different
      times. Cell proliferation was determined by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5
      di-phenytetrazoliumromide assay. Cell apoptosis was evaluated by flow cytometry
      and caspases activities assay. The expression of several proapoptotic proteins
      belonging to the Bcl-2 family, such as Bax, Bim, and Bad, was detected by Western
      blot. RESULTS: Oleanen mainly inhibited the proliferation of HeLa cells at the G0
      to G1 and G2 to M phases, and the IC50 of oleanen for cells was significantly
      higher at 24 hours compared to 48 hours (17.45 +/- 3.71 vs 9.02 +/- 0.83 MUg/mL,
      respectively; P < 0.05). The significant increase in activity of caspase 3/7,
      caspase 6 in oleanen-treated HeLa cells indicated that oleanen promoted the
      apoptosis of HeLa cells. The activity of caspase 9 representing the endogenous
      apoptotic pathways also increased obviously in oleanen treatment. Furthermore,
      the increase in the expression of Bim was the most significant among the Bcl-2
      family after oleanen treatment. CONCLUSION: Oleanen up-regulates the expression
      of Bim and other proapoptotic molecules to activate the endogenous apoptosis
      pathway, thus promoting apoptosis and inhibiting proliferation of human cervical
      cancer HeLa cells in vitro.

PMID- 21897271
TI  - Analysis of 4 single-nucleotide polymorphisms in relation to cervical dysplasia
      and cancer development using a high-throughput ligation-detection reaction
      procedure.
AB  - BACKGROUND: Host genetic characteristics and environmental factors may correlate
      with risk for cervical cancer development. Here we describe a retrospective
      screening study for single nucleotide polymorphisms (SNPs) in genetic markers
      TP53, MTHFR, CYP1A1, and CYP2E1 in 749 patients. METHODS: A multiplex ligation
      dependent polymerase chain reaction approach was applied. We used archived
      material from human papillomavirus tests and correlated SNP genotypes to the
      corresponding clinical data. Semantic integration was used to identify and
      evaluate the clinical status from electronic health records. RESULTS: An
      association with cervical cancer and high-grade dysplasia was found for the rare
      homozygous CC genotype (rs4646903) in CYP1A1 (odds ratio [OR], 8.862). Odds
      ratios were also significantly elevated for heterozygous MTHFR CT genotype
      (rs1801133; OR, 1.457). No significant association was found in TP53 (rs1042522)
      and CYP2E1 (rs3813867). In addition, we found smokers at higher risk (OR, 2.688)
      and identified pregnancies as a significant risk factor (OR, 1.54). CONCLUSIONS:
      Our protocol enables a feasible way for further retrospective large sample size
      evaluation of potential genetic markers. This study revealed genetic associations
      of a rare SNP genotype with cervical dysplasia in one of the largest patient
      sample to date that warrants further investigation.

PMID- 21897272
TI  - Association of survivin gene polymorphism with endometrial cancer.
AB  - OBJECTIVE: Survivin is an inhibitor of apoptosis protein, which is up-regulated
      in endometrial cancer (EC). A promoter region polymorphism (-31G/C) in the
      survivin gene has been reported as a modulator of gene expression. The aim of
      this study was to explore the frequency of survivin -31G/C polymorphism in tumor
      tissues from patients with EC in an Iranian population compared to that of
      healthy controls. MATERIALS AND METHODS: Paraffin-embedded tissue sections from
      patients diagnosed with EC (n = 31) and healthy controls (n = 30) were examined.
      Genotyping for survivin -31G/C polymorphism was performed using polymerase chain
      reaction (PCR) restriction fragment length polymorphism (RFLP). RESULTS: The
      presence of allele C was found to be significantly increased in EC tissues
      compared to the healthy tissues (GG vs GC + CC, P = 0. 01; OR, 3.6; 95% CI, 1.1
      11.9). CONCLUSION: Our data are in keeping with a previous finding regarding the
      role of survivin gene polymorphism in malignancies. This finding highlights the
      role of survivin in pathogenesis of various carcinomas, which might have
      therapeutic implications.

PMID- 21897274
TI  - Conservative therapy in microinvasive adenocarcinoma of the uterine cervix is
      justified: an analysis of 59 cases and a review of the literature.
AB  - OBJECTIVE: This study aimed to evaluate the treatment and follow-up in a large
      series of women with early cervical adenocarcinoma (AC), stages IA1 and IA2, and
      to perform an extensive review of the literature in an effort to ascertain
      whether conservative therapy is justified. METHODS: Records of 59 cases of
      microinvasive AC diagnosed between 1987 and 2006 in the Rotterdam district, the
      Netherlands, were retrieved. Clinical and pathological data were reviewed and
      analyzed. A mesh review of all relevant literature concerning stage IA1 and IA2
      was performed. RESULTS: Of all patients, 33 had stage IA1 and 26 stage IA2
      cervical AC. Also, 42 patients were treated conservatively (ie, conization or
      simple hysterectomy) and 17 patients were treated radically (ie, radical
      hysterectomy/trachelectomy with lymph node dissection). Recurrence occurred in 1
      patient (1.7%) with stage IA1 disease (grade 1 adenocarcinoma, depth 1.4 mm, and
      width 3.8 mm, with lymph vascular space involvement [LVSI]) treated by vaginal
      hysterectomy. The mean follow-up was 79.9 months. From the literature, pooling
      all data from patients with stage IA1 and IA2 AC, the risk of recurrent disease
      was 1.5% after conservative therapy and 2.0% after radical therapy. CONCLUSIONS:
      Extensive treatment such as radical hysterectomy with pelvic lymph node
      dissection or trachelectomy does not prevent recurrent disease. Patients with
      microinvasive AC should be treated identically to patients with SCC. In stage IA1
      and IA2 AC, we recommend conservative therapy (by conization). In cases with
      LVSI, an additional lymphadenectomy is advised. For patients with stage IA2 AC
      with LVSI, a trachelectomy/radical hysterectomy with lymph node dissection should
      be considered.

PMID- 21897273
TI  - Loss of BRCA1 protein expression as indicator of the BRCAness phenotype is
      associated with favorable overall survival after complete resection of sporadic
      ovarian cancer.
AB  - OBJECTIVE: Hereditary epithelial ovarian cancers (EOCs) not expressing functional
      BRCA1 protein are characterized by defects in homologous recombination DNA
      repair, rendering such tumors more sensitive to DNA damaging agents and synthetic
      lethality, that is, poly-ADP-ribose-polymerase inhibitor treatment. The aim of
      this study was to evaluate the use of BRCA1 immunohistochemistry (IHC) for EOC
      prognosis and identification of features of the BRCAness phenotype. METHODS:
      Twenty-seven patients who were treated for advanced EOC by macroscopic complete
      surgical tumor resection and first-line carboplatin/paclitaxel treatment were
      included. Time to recurrence and overall survival time after initial surgery were
      determined, and patients' samples were evaluated for BRCA1 expression by IHC.
      BRCA1 messenger RNA expression and promoter methylation was analyzed to elucidate
      regulatory mechanisms involved in BRCA1 protein loss. RESULTS: BRCA1 IHC-negative
      patients had a significantly longer overall survival (crude rate, 1537 days)
      compared to the BRCA1 IHC-positive group (crude rate, 827 days; P = 0.01). The
      patients in the BRCA1 IHC-negative group were significantly younger (51 years)
      compared to BRCA1 IHC-positive patients (61 years; P < 0.01). Importantly, both
      transcriptional and posttranscriptional mechanisms regulate BRCA1 protein
      expression. Only protein but not messenger RNA level were associated with longer
      overall survival. CONCLUSION: Epithelial ovarian cancers with negative BRCA1
      protein expression were identified in younger patients, showed a significantly
      better overall survival, prolonged treatment intervals and a tendency for an
      extended progression free time interval. BRCA1 IHC negativity of sporadic EOC may
      be predictive of sensitivity to platinum-based chemotherapy and the poly-ADP
      ribose-polymerase inhibitor-sensitive BRCAness phenotype.

PMID- 21897275
TI  - Antrodia camphorata induces apoptosis and enhances the cytotoxic effect of
      paclitaxel in human ovarian cancer cells.
AB  - INTRODUCTION: Antrodia camphorata is a Chinese herb. Recently, several reports
      demonstrated that it had growth-inhibiting effects on some cancer cells. In this
      study, we investigated whether the crude extract of A. camphorata could inhibit
      the growth of ovarian cancer cells and examined the possible mechanisms involved.
      We also examined whether the cytotoxic effect of paclitaxel on ovarian cancer
      cells would be affected by A. camphorata. MATERIALS AND METHODS: Two human
      ovarian cancer cell lines, SKOV-3 and TOV-21G, were treated with A. camphorata (3
      300 MUg/mL). An MTT assay was used to test its cytotoxic effect. The apoptosis
      related factors including the activity of caspase-3, -8, and -9 and the
      cytochrome c level released from mitochondria were analyzed. The expression of
      Bcl-2 family proteins (Bcl-2, Bcl-xL, Bax, Bim, Bad, and Bak) was examined by
      Western blot analysis. Cell lines were further treated with paclitaxel or
      paclitaxel plus A. camphorata to examine the cytotoxic efficiency. RESULTS: The
      MTT assay revealed that A. camphorata was cytotoxic to both the ovarian cancer
      cells in a dose- and time-dependent manner. Activities of caspase-3, -8, and -9
      and release of mitochondrial cytochrome c increased in both ovarian cancer cell
      lines with increased dose of A. camphorata. Western blot analysis of Bcl-2 family
      proteins revealed an increased expression of Bad in SKOV-3 cells, whereas
      increased expression of Bim and Bak and decreased expression of Bcl-xL were noted
      in TOV-21G cells. In addition, the cytotoxic effect of paclitaxel on SKOV-3 and
      TOV-21G cells was increased significantly with the addition of A. camphorata (P <
      0.01) by MTT assay. CONCLUSIONS: These in vitro results suggest that A.
      camphorata causes a cytotoxic effect on ovarian cancer cells through the
      induction of apoptosis. It may also enhance the antitumor effect of paclitaxel.
      Further studies with the ultimate goal of conducting clinical trials are
      warranted.

PMID- 21897276
TI  - Participation in community and political life of persons with severe
      disabilities.
AB  - Participation as a citizen, that is, engaging in social, political, and
      governmental life, has been rarely seen as an important domain when studying
      social participation of disabled persons. The purpose of this study was to depict
      the participation in community and political life of persons with severe or
      multiple disabilities and to determine which individual and social factors were
      associated with their participation. Altogether, 818 persons, who had
      participated in rehabilitation for persons with severe disabilities, answered the
      questionnaire survey. They reported how actively they participated in
      associations, local congregations, political parties, or public elections. Active
      participation in community and political life was strongly connected to
      participation in work, social, and leisure activities, as well as to the use of
      computers. According to stepwise multiple logistic regression analysis, the
      strongest predictors for active participation in community and political life
      were age of disablement, the individual's present age, self-rated income, self
      rated quality of life, use of assistive devices, and the ability to communicate.

PMID- 21897277
TI  - Development of the Arab heritage Activity Card Sort.
AB  - Participation is an indicator of healthy functioning and well-being, as
      emphasized by the International Classification of Functioning, Disability, and
      Health (World Health Organization, 2001). The Activity Card Sort (ACS) is a valid
      and reliable assessment tool that measures participation. This study describes
      the process of developing the Arab heritage version of the ACS (A-ACS). The
      original ACS was translated to Arabic using World Health Organization forward
      backward translation guidelines, and activities that are common in Arab cultures
      were nominated using the ACS investigators' guidelines. Participant respondents
      were 156 Jordanians, from different age groups and socioeconomic classes. The
      process initially yielded 179 activities common to all international versions of
      the ACS, 19 of which were unique to the Arab culture. Eighty-eight items were
      validated for the A-ACS. The A-ACS validated in this study is the first
      assessment tool, for Arab adults whose heritage is in the Middle-East and North
      Africa, that measures participation. We expect the tool to have excellent
      clinical utility not only in Arab countries, but also for immigrants and citizens
      of Arab origins worldwide.

PMID- 21897278
TI  - An unusual case of coronary fistula diagnosed by multidetector computed
      tomography.
AB  - We present a case of a 82-year-old hypertensive woman who underwent multidetector
      computed tomography angiography because of chest pain, with detection of a large
      coronary fistula that originated from the anastomosis between left anterior
      descending coronary artery and posterior descending artery, in correspondence
      with the left ventricular apex, and drained into the right atrium and the
      proximal portion of the right coronary artery.

PMID- 21897279
TI  - The heart in an airbag:  spontaneous pneumopericardium in a young lady.
AB  - Pneumopericardium is a rare but potentially life-threatening clinical condition
      that must be considered in the differential diagnosis of chest pain. It is
      usually associated with chest trauma, infections, invasive procedures or
      mechanical ventilation. We report a case of pneumopericardium in a 25-year-old
      woman following a recent episode of forceful vomiting possibly acting as trigger
      factor. The diagnosis was made by posteroanterior chest radiography and confirmed
      with computed tomography. Contrast swallow test failed to detect
      oesophagopericardial fistulae and the patient was managed conservatively without
      further complication.

PMID- 21897280
TI  - Successful treatment of a bleeding umbilical varix by percutaneous umbilical vein
      embolization with sclerotherapy.
AB  - Bleeding caused by ectopic varices is an uncommon but important and life
      threatening complication of portal hypertension. Spontaneous external hemorrhage
      from a recanalized umbilical varix is an extremely rare source of ectopic
      variceal bleeding. We report on the acute presentation of a patient with a
      bleeding umbilical varix and successful treatment with percutaneous umbilical
      vein embolization with sclerotherapy. This previously unreported technique is
      described, which adds a new therapeutic option for the management of this
      challenging clinical dilemma. A discussion on the recognition and management of
      ectopic varices is also provided.

PMID- 21897281
TI  - Plasma citrulline concentration as a marker for disease activity in patients with
      Crohn's disease.
AB  - BACKGROUND: Citrulline is a nitrogen end product produced from the intermediary
      metabolism of glutamine through the enzymatically mediated urea cycle, almost
      exclusively in the enterocytes of small intestinal epithelium, with some
      synthesis in colonocytes. Intestinal dysfunction resulting from intestinal
      diseases or injuries affects intermediary metabolism, which includes citrulline
      synthesis. We sought to determine whether plasma citrulline was a biomarker for
      disease activity in patients with Crohn's disease with the hypothesis that
      citrulline concentration would be reduced during active disease. METHODS: A total
      of 81 outpatients aged 18 to 65 years (mean, 40.6+/-15.4 y) with a known history
      of Crohn's disease were studied prospectively. Patients with prior small
      intestinal resection, or renal or hepatic insufficiency were excluded. Crohn's
      disease activity was measured by Harvey-Bradshaw Index (HBI) and was correlated
      to the plasma citrulline concentration measured simultaneously (ion
      chromatography). Spearman correlation coefficients were used to assess for an
      association between the 2 variables. Subgroup analyses of patients with isolated
      small intestinal disease and endoscopically or radiologic verified disease
      activity were also performed. RESULTS: Twenty-two patients had isolated colonic
      disease and 59 had small intestinal involvement. Twenty-six of these patients had
      concurrent endoscopy and/or computed tomography or magnetic resonance imaging. On
      the basis of HBI scores, 32 patients had active disease (HBI >=5) and 49 patients
      had inactive disease. The mean HBI scores were 4.8+/-5.5. The mean plasma
      citrulline concentration was normal, although was below normal in some patients.
      However, it failed to distinguish between active and inactive patients based on
      the HBI (active 27.8+/-8.8 MUmol/L, inactive 27.8+/-11.1 MUmol/L, P=0.991). There
      was no significant linear association between the ranks of citrulline and ranks
      of HBI (rs=0.012, P=0.915). Of the 59 patients with isolated small intestinal
      disease, there was no association between plasma citrulline concentration and the
      HBI (Spearman correlation coefficient, 0.073; P=0.583). There was no difference
      in plasma citrulline concentrations among those with confirmed inflammation by
      imaging or endoscopy (confirmed, 26.2+/-11.8; negative, 28.0+/-10.0; independent
      t test P=0.583). CONCLUSIONS: Plasma citrulline concentration was not a marker of
      disease activity in patients with Crohn's disease. However, all patients studied
      were outpatients and it is possible that plasma citrulline concentration may be
      depressed only in patients with more severe disease or extensive small bowel
      involvement. In addition, plasma citrulline may be increased in the
      postabsorptional state, and for the most part, our patients were nonfasting. More
      studies are needed to further elucidate the role of citrulline as a marker of
      disease activity in patients with Crohn's disease. The possibility also exists
      that citrulline may be a better marker in patients with previous resection, and
      this group will require specific evaluation.

PMID- 21897282
TI  - Beyond the Milan criteria: what risks for patients with hepatocellular carcinoma
      progression before liver transplantation?
AB  - BACKGROUND: To date the selection of the best candidates for liver
      transplantation (LT) owing to hepatocellular carcinoma (HCC) has been mainly
      based on tumor morphological characteristics (nodule diameter and number), which
      have resulted to be independent risk factors for short long-term survival and a
      high rate of tumor recurrence. METHODS: The study cohort included 118 patients
      among the 166 with HCC transplanted at our unit from January 2000 to December
      2007. Patients were classified according to response to locoregional treatments
      before LT: progressive Group A; complete Group B; partial Group C; stable Group
      D. RESULTS: The 3-year and 5-year overall survival rates were 65.5% and 48.9% for
      Group A versus 84.8% and 74.6% for Group BCD (P = 0.01). The 3-year and 5-year
      disease-free survival rates were 74% and 74% for Group A and 95.7% and 93% for
      Group BCD (P = 0.007). HCC progression was the only independent risk factor
      according to Cox regression P = 0.014--odds ratio 4.4 (1.35-14.3). CONCLUSION:
      After aggressive HCC treatment before LT, imaging progression while on the
      waiting list was a strong predictor of high HCC recurrence rate also in patients
      who met the Milan criteria. Lack of imaging progression can contribute toward the
      selection of good transplant candidates for HCC together with the Milan criteria.

PMID- 21897283
TI  - The complex exocrine-endocrine relationship and secondary diabetes in exocrine
      pancreatic disorders.
AB  - The pancreas is a dual organ with exocrine and endocrine functions. The
      interrelationship of the endocrine-exocrine parts of the pancreas is a complex
      one, but recent clinical and experimental studies have expanded our knowledge.
      Many disorders primarily of the exocrine pancreas, often solely in the clinical
      realm of gastroenterologists are associated with diabetes mellitus (DM).
      Although, the DM becoming disorders are often grouped with type 2 diabetes, the
      pathogenesis, clinical manifestations and management differ. We review here data
      on the association of exocrine-endocrine pancreas, the many hormones of the
      pancreas and their possible effects on the exocrine functions followed by data on
      the epidemiology, pathogenesis, and management of DM in chronic pancreatitis,
      cystic fibrosis, pancreatic cancer, and clinical states after pancreatic surgery.

PMID- 21897284
TI  - Metastatic lung adenocarcinoma to the iris mimicking Cogan-Reese syndrome.
AB  - PURPOSE: Case report of metastatic lung cancer to the iris mimicking Cogan-Reese
      syndrome. METHODS: A 61-year-old female with a history of non-small cell lung
      cancer presented with unilateral elevated intraocular pressure (IOP) and multiple
      hyperpigmented iris nodules associated with an anterior iris membrane. The
      patient's IOP could not be controlled medically, so she underwent trabeculectomy
      with simultaneous iris biopsy. RESULTS: Histopathology revealed proliferation of
      glandular epithelium on the iris surface consistent with metastatic lung
      adenocarcinoma. CONCLUSIONS: Iris metastases have varied presentations, and one
      must consider metastatic disease in any patient with a history of cancer
      presenting with iris lesions. The formation of an iris membrane and nodules by
      metastatic adenocarcinoma to the iris may mimic Cogan-Reese syndrome.

PMID- 21897285
TI  - Intraocular pressure and associated factors: the central India eye and medical
      study.
AB  - PURPOSE: To determine the range of intraocular pressure (IOP) in a rural Central
      Indian population and to evaluate existing and identify potential new ocular,
      medical, and socioeconomic factors associated with IOP. METHODS: This is a
      population-based study carried out in Nagpur in Central India. A single IOP
      measurement was taken using Goldmann applanation tonometry and population IOP was
      described using standard descriptive statistics. RESULTS: Of 5885 eligible
      patients, 9338 eyes of 4686 patients were included in the study. The mean IOP was
      13.6+/-3.4 mm Hg (median: 14 mm Hg; range: 2 to 56 mm Hg). In multivariate
      regression analysis, the following factors, with correlation coefficients (r) and
      P values reported in parenthesis, were found to be associated with IOP. Ocular
      factors included higher corneal power (0.12; P=0.004), lower central corneal
      thickness (0.02; P<0.001), and higher myopic refractive power (-0.13; P=0.001).
      Medical factors included diastolic blood pressure (0.05; P<0.001), pulse rate
      (0.02; P=0.005), and body mass index (0.05; P=0.01). Socioeconomic factors
      included level of education (0.15; P=0.05) and livestock ownership (-0.18;
      P=0.008). CONCLUSION: Low mean IOP was found when compared with other
      epidemiologic studies and this may be explained by the low central corneal
      thickness found in the study population. Several known ocular and medical factors
      and new socioeconomic factors were found to be associated with IOP. Identifying
      risk factors associated with IOP in different populations may allow clinicians to
      better define and recognize subgroups of patients at risk of elevated IOP. Newly
      identified socioeconomic-IOP associations will need to be validated in future
      studies.

PMID- 21897286
TI  - Influence of bodily injuries on symptom reporting following uncomplicated mild
      traumatic brain injury in US military service members.
AB  - OBJECTIVE: : To examine the relations among bodily injuries, traumatic stress,
      and postconcussion symptoms in a sample of combat-injured US service members who
      sustained a mild traumatic brain injury. PARTICIPANTS: : One hundred and thirty
      seven service members evaluated and treated at Walter Reed Army Medical Center
      following medical evacuation from the combat theater of Operation Enduring
      Freedom and Operation Iraqi Freedom. All had sustained an uncomplicated mild
      traumatic brain injury and concurrent bodily injuries. PROCEDURE: : Participants
      completed 2 symptom checklists within 3 months of injury. Severity of bodily
      injuries was quantified with a modified version of the Injury Severity Score that
      excluded intracranial injuries (ISSmod). Participants were classified into 4
      ISSmod groups: minor (n = 17), moderate (n = 48), serious (n = 40),
      severe/critical (n = 32). MAIN OUTCOME MEASURES: : Neurobehavioral Symptom
      Inventory (NBSI) and the Posttraumatic Stress Disorder Checklist-Civilian version
      (PCLC). RESULTS: : There was a significant negative association between ISSmod
      scores and the NBSI and PCLC total scores. There were significant main effects
      across the 4 groups for the NBSI and PCLC total scores. The highest NBSI and PCLC
      scores were consistently found in the ISSmod minor group, followed by the
      moderate, serious, and severe/critical groups. CONCLUSIONS: : While it might be
      expected that greater comorbid physical injuries would be associated with greater
      symptom burden, in this study as the severity of bodily injuries increased,
      symptom burden decreased. Hypothesized explanations include: underreporting of
      symptoms; increased peer support; disruption of fear conditioning due to acute
      morphine use; or delayed expression of symptoms.

PMID- 21897287
TI  - Psychometric properties and feasibility of instruments used to assess awareness
      of deficits after acquired brain injury:  a systematic review.
AB  - BACKGROUND: Unawareness of deficits after acquired brain injury (ABI) is often
      reported in the clinic. Several methods have been developed to measure a
      patient's awareness of deficits after ABI; however, no criterion standard
      currently exists to measure this phenomenon. OBJECTIVE: To review all instruments
      for measuring awareness of deficits and evaluate their psychometric and
      conceptual properties as well as their feasibility. METHODS: Systematic
      literature search for available awareness measurement instruments used in
      experimental ABI studies. Instruments were divided into the following 4
      assessment methods: clinician ratings, structured interviews, performance-based
      discrepancy, and self-other rating discrepancy methods. The quality of the
      instruments was evaluated. RESULTS: The literature search identified 39
      instruments and 8 of these were selected. The following 3 instruments stood out
      in terms of quality: Self-Awareness of Deficits Interview, Patient Competency
      Rating Scale, and Awareness Questionnaire. CONCLUSION: Although these
      quantitative instruments are useful tools in research, they have limited utility
      in the clinic because they only measure intellectual awareness. Therefore, in
      addition to these instruments, qualitative tools should also be used to gain a
      complete view of a patient's awareness problem.

PMID- 21897288
TI  - Representativeness of the Traumatic Brain Injury Model Systems National Database.
AB  - OBJECTIVE: To determine whether the Traumatic Brain Injury Model Systems National
      Database (TBIMS-NDB) is representative of individuals aged 16 years and older
      admitted for acute, inpatient rehabilitation in the United States with a primary
      diagnosis of traumatic brain injury (TBI). DESIGN: Secondary analysis of existing
      data sets. SETTING: Acute inpatient rehabilitation facilities. PARTICIPANTS:
      Patients aged 16 years and older with a primary rehabilitation diagnosis of TBI.
      MAIN OUTCOME MEASURES: Demographic characteristics, functional status, and
      hospital length of stay. RESULTS: Patients included in the TBIMS-NDB from October
      2001 through December 2007 were largely representative of all individuals 16
      years and older admitted for rehabilitation in the United States with a primary
      diagnosis of TBI. The major difference in distribution was age-the TBIMS-NDB
      cohort did not include as large a proportion of patients older than 65 years as
      were admitted for rehabilitation with a primary diagnosis of TBI in the United
      States. Distributional differences for age-related characteristics were observed;
      however, groups of patients partitioned at aged 65 years differed minimally,
      especially within the younger than 65 years subset. Regardless of age, the
      proportion of patients with a rehabilitation stay of 1 to 9 days was larger
      nationwide. Nationwide admissions showed an age distribution similar to patients
      discharged alive from acute care with moderate, severe or penetrating TBI. The
      proportion of patients aged 70 years and older admitted for TBI rehabilitation in
      the United States increased every year, a trend that was not evident in the
      general population, TBIMS-NDB or among TBI patients in acute care. CONCLUSIONS:
      These results provide substantial empirical evidence that the TBIMS-NDB is
      representative of patients receiving inpatient rehabilitation for TBI in the
      United States. Researchers utilizing the TBIMS-NDB may want to adjust
      statistically for the lower percentage of patients older than 65 years or those
      with stays less than 10 days.

PMID- 21897289
TI  - Prediction of driving capacity after traumatic brain injury:  a systematic
      review.
AB  - OBJECTIVE: To review the current evidence on predictors for the ability to return
      to driving after traumatic brain injury. METHODS: Systematic searches were
      conducted in MEDLINE, PsycINFO, EMBASE, and CINAHL up to March 1, 2010. Studies
      were rigorously rated for their methodological content and quality and
      standardized data were extracted from eligible studies. RESULTS: We screened 2341
      articles, of which 7 satisfied our inclusion criteria. Five studies were of
      limited quality because of undefined, unrepresentative samples and/or absence of
      blinding. Studies mentioned 38 candidate predictors and tested 37. The candidate
      predictors most frequently mentioned were "selective attention" and "divided
      attention" in 4/7 studies, and "executive functions" and "processing speed," both
      in 3/7 studies. No association with driving was observed for 19 candidate
      predictors. Eighteen candidate predictors from 3 domains were associated with
      driving capacity: patient and trauma characteristics, neuropsychological
      assessments, and general assessments; 10 candidate predictors were tested in only
      one study and 8 in more than one study. The results of associations were
      contradictory for all but one: time between trauma and driving evaluation.
      CONCLUSIONS: There is no sound basis at present for predicting driving capacity
      after traumatic brain injury because most studies have methodological
      limitations.

PMID- 21897290
TI  - Ethical implications of neuroimaging in sports concussion.
AB  - The Centers for Disease Control and Prevention estimates that 1.6 to 3.8 million
      traumatic brain injuries that occur each year are related to sports injuries. New
      research has broadened the understanding of the acute and chronic pathophysiology
      of concussion associated with brain injury, and recent advances in diagnostic
      capabilities with neuroimaging are leading to new ethical questions around sport
      and care of the head-injured athlete. In this review, we synthesize the current
      literature on neuroimaging for assessing concussed athletes and explore ethical
      issues in the context of return to play, short- and long-term neurologic health
      effects following concussion and resource allocation that are emerging with new
      implications as neurotechnology becomes an increasingly powerful tool on the
      playing field of health.

PMID- 21897291
TI  - Normobaric hypoxia conditioning reduces blood pressure and normalizes nitric
      oxide synthesis in patients with arterial hypertension.
AB  - OBJECTIVES: Insufficient production and/or increased decomposition of the potent
      endogenous vasodilator nitric oxide plays an important role in development and
      progression of arterial hypertension and its complications. One of the most
      effective means of stimulating endogenous nitric oxide synthesis is controlled
      adaptation to hypoxia. This study examined the effect of a 20-day, intermittent,
      normobaric intermittent hypoxia conditioning (IHC) program on blood pressure (BP)
      and nitric oxide production in patients with stage 1 arterial hypertension.
      METHODS: The IHC sessions consisted of four to 10 cycles of alternating 3-min
      hypoxia (10% FIO2) and 3-min room air breathing. BP was monitored for 24 h before
      and after IHC, and nitric oxide synthesis was evaluated by 24-h urinary excretion
      of the stable nitric oxide metabolites nitrate and nitrite. RESULTS: IHC
      increased nitric oxide synthesis and decreased BP in hypertensive patients to
      values similar to those of normotensive individuals. Significant inverse
      correlations were found between nitric oxide production and disease duration,
      SBP, and DBP. Moreover, IHC enhancement of nitric oxide synthesis was especially
      robust in patients with arterial hypertension of more than 5 years duration. The
      reduction in BP persisted for at least 3 months in 28 of 33 hypertensive
      patients. CONCLUSION: IHC exerted a robust, persistent therapeutic effect and can
      be considered as an alternative, nonpharmacological treatment for patients with
      stage 1 arterial hypertension. The antihypertensive action of IHC is associated
      with normalization of nitric oxide production.

PMID- 21897292
TI  - Residual beneficial effects after a 3-year integrated intervention on stroke in
      China:  a 10-year prospective follow-up.
AB  - OBJECTIVES: To evaluate whether an intervention program designed to reduce stroke
      incidence would have long-term residual effects on reducing all-cause and cause
      specific mortalities, including cancer 10 years after the intervention was
      completed. METHODS: This is a posttrial analysis. We prospectively observed the
      mortality of a community-based trial of primary prevention of stroke in China
      performed between July 1987 and June 1990 by extending the follow-up to 30 June
      2000. At the baseline, 26,607 adults aged 35 years or above and free from stroke
      were recruited from five cites of mainland China; 13,212 and 13,395 were assigned
      into intervention and control group, respectively. Participants in intervention
      group received a regularly integrated intervention including lifestyle
      intervention and hypertensive drug treatment. The controls did not receive
      intervention provided by the investigators. RESULTS: During the 10-year posttrial
      follow-up period, we observed a significant reduction on overall deaths [hazard
      ratio 0.91; 95% confidence interval (CI) 0.83, 0.99] and stroke mortality (hazard
      ratio 0.79; 95% CI 0.63, 1.00). An insignificant late trial beneficial effect was
      observed for hypertensive disease (hazard ratio 0.69; 95% CI 0.30, 1.58),
      ischemic heart disease (hazard ratio 0.87; 95% CI 0.64, 1.17), other nonmalignant
      diseases, and most cancer sites. CONCLUSION: This study demonstrates that a 3
      year integrated intervention program successful for stroke prevention had long
      term residual beneficial effects on reducing overall disease burdens among urban
      Chinese population, especially for the deaths from stroke. However, whether the
      integrated intervention also leads to reduced mortality of cardiovascular
      diseases and cancer would have to be confirmed by future larger studies.

PMID- 21897293
TI  - Continuing smoking between adolescence and young adulthood is associated with
      higher arterial stiffness in young adults:  the Northern Ireland Young Hearts
      Project.
AB  - OBJECTIVES: To investigate the associations between smoking in adolescence and
      adulthood, and changes in smoking behaviour between these age periods, with
      arterial stiffness in young adults; and whether any such associations could be
      explained by concomitant smoking-related levels of inflammation and endothelial
      dysfunction. METHODS: We studied 424 individuals (216 women) in whom smoking
      status was assessed in adolescence (age 15 years) and again in young adulthood
      (mean age of 22.6 +/- 1.6 years), along with aorto-iliac, aorto-radial, and aorto
      dorsalis pedis pulse wave velocity (PWV), and markers of inflammation (i.e. C
      reactive protein and fibrinogen) and endothelial dysfunction (i.e. von Willebrand
      factor and tissue-plasminogen activator antigen) in young adulthood only.
      RESULTS: Smoking in adolescence was associated with higher aorto-iliac PWV, as
      well as with inflammation and endothelial dysfunction levels (expressed as two
      scores), independently of other adolescent and adult lifestyles. Compared with
      never smokers, continuing smokers, but not starters nor quitters, showed higher
      aorto-iliac PWV, independent of changes in other lifestyle variables: +0.157 m/s
      (95% confidence interval 0.026-0.288). This difference was attenuated to 0.124
      m/s (-0.009 to 0.257) after adjustment for changes in traditional biological risk
      factors, but was not materially affected when adjusted for the inflammation and
      endothelial dysfunction scores, despite the continuing smoking-related higher
      levels of inflammation and endothelial dysfunction. Smoking was not associated
      with aorto-radial and aorto-dorsalis pedis PWV. CONCLUSION: Starting to smoke in
      adolescence and continuing to do so up to young adulthood is adversely associated
      with aortic stiffness. The continuing smoking-related aortic stiffness was not
      explained by concomitant higher inflammation and endothelial dysfunction.
      Prevention of smoking should target the young to prevent arterial stiffness in
      young adults.

PMID- 21897294
TI  - Atorvastatin reduces sympathetic activity in patients with chronic kidney
      disease.
AB  - BACKGROUND: Hypertensive chronic kidney disease (CKD) patients often have
      sympathetic hyperactivity, which appears to contribute to the pathogenesis of
      hypertension and cardiovascular organ damage. Experimental studies and some
      clinical studies have shown that statin therapy can reduce central sympathetic
      activity. Blockade of the renin-angiotensin system (RAS), which is standard
      treatment for CKD, is known to lower sympathetic activity. We hypothesized that
      adding a statin for 6 weeks to RAS blockade would further lower sympathetic
      activity in hypertensive stage 2-4 CKD patients. METHODS: In 10 stable CKD
      patients (eight men, aged 45 +/- 11 years, estimated glomerular filtration rate
      56 +/- 22 ml/min per 1.73 m2), who were on chronic treatment with aliskiren 300
      mg, blood pressure and sympathetic activity (quantified by assessment of muscle
      sympathetic nerve activity, MSNA) were assessed at baseline and 6 weeks after
      atorvastatin 20 mg/day was added. Ten other CKD patients served as time control
      and were studied twice with an interval of 6 weeks without any change in
      medication, to quantify within participant reproducibility. RESULTS: Mean
      arterial blood pressure remained stable throughout the study (93 +/- 5 versus 94
      +/- 5 mmHg). MSNA was reduced from 28 +/- 8 to 20 +/- 6 bursts/min (P = 0.01),
      while heart rate remained stable during the study. In the control CKD group, MSNA
      did not change: 26 +/- 5 to 25 +/- 6 bursts/min. Atorvastatin reduced total and
      low-density lipoprotein cholesterol. CONCLUSION: Atorvastatin has a further
      sympatholytic effect in CKD patients, who are on chronic aliskiren, which is
      independent of blood pressure and heart rate.

PMID- 21897295
TI  - Postinfectious optic neuropathy in endemic typhus.
AB  - Endemic typhus (Rickettsia typhi), also known as murine typhus, is a flea-borne
      bacterial disease rarely found in most of the developed world. Known ocular
      manifestations linked to endemic typhus include mild vitritis, retinal lesions,
      and retinal vascular leakage. Optic neuropathy, however, is rarely associated
      with R. typhi, and postinfectious optic neuropathy is even less common. To
      highlight this unusual complication, we report a patient who developed
      postinfectious optic neuropathy a few weeks after he was successfully treated for
      endemic typhus.

PMID- 21897296
TI  - A novel technique for monitoring of fast variations in brain oxygen tension using
      an uncoated fluorescence quenching probe (Foxy AL-300).
AB  - BACKGROUND: A novel uncoated fluorescence quenching probe allows fast measurement
      of oxygen tension in vessels and tissue. The present study reports the first use
      of the technology for dual measurements of arterial (paO(2)) and brain tissue
      oxygen tension (ptiO(2)) during hypoxic challenge in a pig model. METHODS: Eight
      pigs were anesthetized using fentanyl and propofol. Fluorescence quenching pO(2)
      probes (Foxy AL-300, Ocean Optics, Dunedin, FL) were placed in the ascending
      aorta (Foxy-paO(2)) and subcortically at 14 mm in brain tissue (Foxy-ptiO(2)). As
      reference, a clark-type electrode probe (Licox-ptiO(2)) was placed into brain
      tissue close to the Foxy probe (Licox, Integra Neurosciences, Plainsboro, NJ).
      Measurements were taken at baseline (FiO(2) 1.0), during episodes of apnea, and
      during recovery (FiO(2) 1.0). STATISTICS: descriptive results. RESULTS:
      Individual Foxy-paO(2), Foxy-ptiO(2), and Licox-ptiO(2) courses were related to
      episodes of apnea. The response time of the Foxy measurements was 10 Hz. Baseline
      values at FiO(2) 1.0 were Foxy-paO(2) 520+/-120 mm Hg, Foxy-ptiO(2) 62+/-24 mm
      Hg, and Licox-ptiO(2) 55+/-29 mm Hg; apnea values were Foxy-paO(2) 64+/-10 mm Hg,
      Foxy-ptiO(2) 37+/-12 mm Hg, and Licox-ptiO(2) 31+/-16 mm Hg; recovery values at
      FiO(2) 1.0 were Foxy-paO(2) 478+/-98 mm Hg, Foxy-ptiO(2) 78+/-26 mm Hg, and Licox
      ptiO(2) 62+/-32 mm Hg. CONCLUSIONS: The present study demonstrates the
      feasibility of pO(2) measurements in macrocirculation and cerebral
      microcirculation using a novel uncoated fluorescence quenching probe. The
      technology allows for real-time investigation of pO(2) changes at a temporal
      resolution of 0.05 to 10 Hz.

PMID- 21897297
TI  - The effect of pressure-controlled ventilation on pulmonary mechanics in the prone
      position during posterior lumbar spine surgery: a comparison with volume
      controlled ventilation.
AB  - BACKGROUND: When an anesthetized patient is turned to the prone position using
      the Wilson frame, dynamic compliance (Cdyn) decreases and peak airway pressure
      (Ppeak) increases. As pressure-controlled ventilation (PCV) decreases the Ppeak,
      this prospective, randomized study was designed to compare the effect of PCV and
      volume-controlled ventilation (VCV) on lung mechanics in the prone position using
      the Wilson frame during posterior lumbar spine surgery. METHODS: Forty patients
      scheduled for posterior lumbar spine surgery were randomly allocated to receive
      mechanical ventilation using either the VCV (n=20) or PCV (n=20) mode.
      Respiratory variables (including Ppeak and Cdyn) and oxygenation parameters were
      recorded at the supine position (Tsupine) and 30 minutes after prone positioning
      (Tprone). RESULTS: During the study period, tidal volume, minute volume, end
      tidal carbon dioxide tension, and positive end-expiratory pressure were
      comparable between the 2 groups. The Ppeak in the PCV group was lower than that
      in the VCV group throughout the study period (P=0.007 and 0.003 at Tsupine and
      Tprone, respectively) and was increased at Tprone compared with Tsupine in both
      groups. Cdyn was decreased from Tsupine to Tprone in both groups. However, the
      Cdyn in the PCV group was higher than that in the VCV group during the study
      period. The arterial oxygen tension was comparable between the 2 groups during
      the study period. CONCLUSIONS: PCV provides lower Ppeak compared with VCV when
      the ventilator is set to deliver the same tidal volume and variable respiratory
      rate to maintain a constant end-tidal carbon dioxide tension in patients
      undergoing posterior lumbar spine surgery in the prone position using the Wilson
      frame.

PMID- 21897298
TI  - Management of post septic hip dislocations when the capital femoral epiphysis is
      present.
AB  - Delayed or missed diagnosis of septic arthritis of hip in children results in
      various sequelae. The group of post septic hip dislocations when the capital
      femoral epiphysis (CFE) is present has not been described in the commonly used
      classifications. This is a retrospective series of 21 hips in 18 children. The
      presence of the CFE was confirmed radiologically or at the time of intervention.
      The mean follow-up after intervention was 6.3 years. Interventions for
      dislocations included closed reduction +/- adductor tenotomy, open reduction +/-
      supplementary femoral procedures, and acetabular procedures. Results were
      evaluated clinically with Ponseti hip scoring and radiologically with the
      modified Severin grading. Closed reduction was successful in seven of 20 hips
      (35%) and open reduction in 13 of 14 hips. At follow-up, good clinical result was
      seen in nine of 18 cases (50%). The mean neck shaft angle was 129 degrees  in all
      hips and 124 degrees  after femoral varus osteotomy. There was one redislocation
      and three subluxations. The modified Severin classification was class 2 in five
      hips (good), class 3 in 12 hips (fair), class 4 in three hips (poor), and class 6
      in one hip (failure). Septic hip dislocation with CFE present is a distinct
      entity. MRI is helpful for planning treatment. A significant number of patients
      need open reduction with other procedures. Femoral varus osteotomy may contribute
      to coxa vara. In the short term, intervention results in a stable, functional,
      and mobile hip.

PMID- 21897299
TI  - Metaphyseo-diaphyseal junction fracture of distal humerus in children.
AB  - Six metaphyseo-diaphyseal junction fractures of distal humerus and 182
      supracondylar fractures of humerus treated in our institute over a period of 5
      years were retrospectively analyzed. Clinical data regarding child's age,
      neurovascular status, mechanism of injury, mode of treatment, and ultimate
      clinical outcome were collected for both these fractures and a comparison was
      made. Oblique (n=2), comminuted (n=3), and transverse types (n=1) of fracture
      patterns were identified at distal humeral metaphyseo-diaphyseal junction. The
      oblique and comminuted fractures were managed by closed reduction and plaster of
      Paris cast, whereas the only transverse fracture was treated by closed reduction
      and Kirschner wire fixation. In contrast, 125 patients of supracondylar fractures
      were treated by closed reduction and plaster of Paris cast and the remaining 57
      fractures needed Kirschner wire fixation after closed reduction. Assessment by
      Flynn criteria after 1 year after of injury revealed better functional outcome in
      metaphyseo-diaphyseal junction fractures. Although transverse fractures are
      unstable and may require surgical fixation; oblique and comminuted fractures at
      the metaphyseo-diaphyseal junction of distal humerus can be managed
      conservatively.

PMID- 21897300
TI  - Physician work intensity among medical specialties: emerging evidence on its
      magnitude and composition.
AB  - BACKGROUND: Similarities and differences in physician work intensity among
      specialties are poorly understood but have implications for quality of care,
      patient safety, practice organization and management, and payment. OBJECTIVE: To
      determine the magnitude and important dimensions of physician work intensity for
      4 specialties. RESEARCH DESIGN: Cross-sectional assessment of work intensity
      associated with actual patient care in the examination room or operating room.
      SUBJECTS: A convenience sample of 45 family physicians, 20 general internists, 22
      neurologists, and 21 surgeons, located in Kansas, Kentucky, Maryland, Ohio, and
      Virginia. MEASURES: Work intensity measures included the National Aeronautics and
      Space Administration-Task Load Index (NASA-TLX), Subjective Work Assessment
      Technique (SWAT), and Multiple Resource Questionnaire. Stress was measured by the
      Dundee Stress State Questionnaire. RESULTS: Physicians reported similar magnitude
      of work intensity on the NASA-TLX and Multiple Resource Questionnaire. On the
      SWAT, general internists reported work intensity similar to surgeons but
      significantly lower than family physicians and neurologists (P=0.035). Surgeons
      reported significantly higher levels of task engagement on the stress measure
      than the other specialties (P=0.019), significantly higher intensity on physical
      demand (P < 0.001), and significantly lower intensity on the performance
      dimensions of the NASA-TLX than the other specialties (P=0.003). Surgeons
      reported the lowest intensity for temporal demand of all specialties, being
      significantly lower than either family physicians or neurologists (P=0.014).
      Family physicians reported the highest intensity on the time dimension of the
      SWAT, being significantly higher than either general internists or surgeons
      (P=0.008). CONCLUSIONS: Level of physician work intensity seems to be similar
      among specialties.

PMID- 21897301
TI  - The effect of distance on the use of emergency hospital services in a Spanish
      region with high population dispersion: a multilevel analysis.
AB  - BACKGROUND: There is geographic variability in the use of hospital emergency
      services. The effect of distance to the hospital on this variability is unknown.
      OBJECTIVES: (a) To analyze the independent effect of distance on use of hospital
      emergency services; (b) to describe the variability among municipalities in use
      of hospital emergency services and to analyze how much of this variability is
      explained by distance. RESEARCH DESIGN: Weighted cross-sectional data from the
      2003 Regional Health Survey of Castile and Leon were linked with municipal-level
      data from the 2001 Census, municipal health resources, and distance from
      municipality to hospital. SUBJECTS: : Sample of 4281 adults residing in 179
      municipalities of the region of Castile and Leon. MEASURES: Using multilevel
      logistic regression models with random intercept, we analyzed the association
      between distance to hospital and use of hospital emergency services. RESULTS: The
      proportion of the sample using hospital emergency services in the last year was
      14.4%. The multivariate analysis showed a significant inverse association between
      distance to hospital and use of emergency services (P=0.001). Use of hospital
      emergency services varied widely across municipalities (variance 0.484; standard
      error 0.132). Some 12.8% of the variability is attributable to differences among
      municipalities. The model explained 31.6% of the variability. CONCLUSION: :
      Distance is a barrier to accessing hospital emergency services. There is large
      variability among municipalities in the use of emergency services not explained
      by the model. Variables related with the capacity of primary care facilities to
      resolve emergencies may reduce part of the observed variability.

PMID- 21897302
TI  - Trends in the treatment and survival for local and regional cutaneous melanoma in
      a US population-based study.
AB  - We examined trends in the treatment and survival in a population-based sample of
      white patients diagnosed with local-stage and regional-stage cutaneous melanoma
      in 1995, 1996, or 2001, treated in communities across the USA with vital status
      follow-up through 2007. White patients, aged 20 years or older with invasive
      cutaneous melanoma, were identified from the Surveillance, Epidemiology and End
      Results population-based registries. Hospital and pathology records were
      reabstracted and physicians were asked to verify the provided therapy. The
      percentage of patients receiving lymph node biopsies increased over time.
      Sentinel lymph node biopsy increased between 1995 and 2001 from 5 to 32% for men
      and from 9 to 35% for women. The use of chemotherapy, hormonal therapy, and
      immunotherapy changed little. Facilities with approved residency training
      programs were more likely to perform lymph node dissections, to perform sentinel
      lymph node biopsy, and to treat patients more aggressively than were facilities
      without such programs. Men were significantly more likely than women to die of
      cutaneous melanoma. In multivariable survival analysis, after adjusting for age,
      Charlson score, and surgical margins, survival did not change significantly over
      this time. Deaths were associated with increasing tumor thickness for men and
      women. Surgical treatment of local or regional melanoma became more extensive
      over time with fewer local excisions and more lymph node dissections, but with
      little change in adjuvant therapy. Survival was associated with tumor thickness.
      Early detection when the tumor thickness is less may decrease mortality. Future
      research should especially target decreasing the disparity in survival between
      men and women.

PMID- 21897303
TI  - Mucosal melanomas of the head and neck:  new aspects of the clinical outcome,
      molecular pathology, and treatment with c-kit inhibitors.
AB  - Approximately 50% of mucosal melanomas affect the head and neck region
      representing approximately 9% of all malignant head and neck tumors. The
      pathogenesis of this disease is unknown. Mucosal melanomas are characterized by
      an aggressive biological behavior, leading to a 5-year survival rate of less than
      25%. Data for this review were identified by searches of Medline, Current
      Contents, PubMed, and references from relevant articles using the terms 'mucosal
      melanoma,' 'head and neck melanoma,' 'c-kit mutation in melanoma,' and 'c-kit
      inhibitors'. Therapy aims for the complete surgical excision of the primary
      tumor, whereas sentinel node biopsy is not established and present data do not
      support the addition of radiotherapy. Mutilating operations of larger tumors
      should be avoided, as they do not inhibit the frequent development of distant
      metastasis. C-kit mutations and amplifications are found in approximately 15-30%
      of mucosal and acral-lentiginous melanomas. Therefore, the use of so-called
      targeted therapies addressing molecular structures in mucosal melanomas seem to
      represent new promising treatment tools. In this study, we review the literature
      regarding epidemiology, molecular pathology, and therapy of mucosal melanomas of
      the head and neck emphasizing c-kit protein inhibiting treatment modalities for
      tumors carrying c-kit mutations.

PMID- 21897304
TI  - Stimulus-induced reduction of noise correlation in rat prefrontal cortex.
AB  - We have shown previously that stimulus-induced modulation of noise correlation in
      rat somatosensory cortex conveys additional information about the delivery of
      tactile stimulation. Here we investigated whether noise correlation is also
      modulated by an external sensory stimulus in rat prefrontal cortex and, if so,
      whether such modulation conveys additional information on stimulus delivery.
      Noise correlation was significantly reduced after the onset of a conditional
      stimulus (auditory tone) that signaled an electric foot shock in the prefrontal
      cortex. However, noise correlation contributed little to the transmission of
      information on stimulus delivery. These results indicate that a meaningful
      sensory stimulus reduces noise correlation in rat prefrontal cortex, but such
      modulation does not play a significant role in conveying information on stimulus
      delivery.

PMID- 21897305
TI  - Individuals' and groups' intentions in the medial prefrontal cortex.
AB  - Functional MRI signal was recorded while participants perceived stimuli presented
      using moving dots. In two conditions of interest, the motion of dots depicted
      intentions: dots representing the joints of an agent performing an action, and
      dots representing individual agents behaving contingently. The finding of a
      common cluster in the posterior part of the medial frontal cortex involved in
      intentional action representation validates the hypothesis that perception of
      these two conditions requires a similar internal representation. A cluster
      responding to the behaving group only is found in the anterior medial frontal
      cortex. These results support a division of the medial frontal cortex according
      to social stimuli attributes, with anterior areas responding to higher-order
      group behaviours integrating the action of multiple individual agents.

PMID- 21897306
TI  - Tc-99m methoxyisobutylisonitrile parathyroid scintigraphy:  the value of adding a
      whole-body scan.
AB  - PURPOSE: The aim of this study was to estimate the frequency of incidental
      findings on Tc-99m-methoxyisobutylisonitrile (MIBI) scan performed for suspected
      parathyroid adenoma and to evaluate the benefit of additional whole-body scan.
      MATERIALS AND METHODS: A total of 109 patients (37 men and 72 women; age range,
      16-96 years; mean, 58.42 years) with clinically suspected parathyroid adenoma
      underwent Tc-99m MIBI whole-body scans and single-photon emission computed
      tomography of the base of the skull, the neck, and the thorax. Each case with
      suspected abnormal tracer accumulation was analyzed and correlated with clinical
      information. RESULTS: MIBI single-photon emission computed tomography of the base
      of the skull, the neck, and the thorax and whole-body scans of 109 patients were
      assessed. A total of five incidental findings were detected. The anatomical
      distribution of the incidental findings was as follows: two (40%) were located in
      the head and neck areas and three (60%) were in the abdomen and pelvis. Two (40%)
      were detected in standard acquisition view, which includes the base of the skull,
      the neck, and the thorax. Three (60%) incidentalomas were detected in whole-body
      scan. In addition, we found 23 cases of abnormal tracer distribution that were
      correlated with known clinical history of patients. Three (13%) were located in
      the head and neck areas, 10 (43.6%) in the thoracic region, six (26%) in the
      abdomen and pelvis, and four (17.4%) in the extremities. CONCLUSION: Whole-body
      imaging in patients with suspected parathyroid adenoma who underwent MIBI scans
      does not alter patient management in most cases.

PMID- 21897307
TI  - Correlation of various published radionuclide glomerular filtration rate
      estimation techniques and proposed paediatric normative data.
AB  - OBJECTIVE: The aim of this study is to assess the comparability and
      interchangeability of the radionuclide glomerular filtration rate (GFR) using
      different published techniques, and propose normative data for paediatrics.
      METHODS: A total of 476 paediatric oncology patients aged 2-17 years, referred
      between January 2001 and December 2008 for GFR estimation, were reviewed for any
      potential cause of renal impairment. Sixty-nine patients met the stringent
      inclusion criteria, and were included in the study. GFR estimation was carried
      out using either technetium-99m diethylene triamine penta-acetic acid (99mTc
      DTPA) or chromium-51 EDTA (51Cr-EDTA). Multiple GFR results were calculated from
      the same blood sample data (counts/min/ml), according to previously published GFR
      estimation techniques using one to three blood samples. These techniques were
      slope-intercept, slope-only and half life. For slope-intercept techniques, GFR
      was normalized to body surface area or extracellular fluid volume. RESULTS: The
      GFR values obtained using different techniques were highly variant. The
      intraclass correlation (ICC) for different methods was moderate (ICC=0.56-0.66).
      A reliable empiric formula to allow conversion of GFR values from one technique
      to another could not be derived because of this variability, with some
      exceptions. 51Cr-EDTA yielded the same or lower variability than 99mTc-DTPA. The
      British Nuclear Medicine Society-recommended method had the lowest coefficient of
      variation, with a mean value of 116 (SD 22) normalized to 1.73 m2 for 51Cr-EDTA
      using two samples. CONCLUSION: The GFR values obtained from different calculation
      techniques are not readily interchangeable or comparable, with some exceptions.
      For both 99mTc-DTPA and 51Cr-EDTA, the British Nuclear Medicine Society
      recommended technique appears to be the most robust, with the least coefficient
      of variation.

PMID- 21897308
TI  - The value of attenuation correction by hybrid SPECT/CT imaging on infarct size
      quantification in male patients with previous inferior myocardial infarct.
AB  - BACKGROUND: Attenuation correction (AC) has been shown to improve the accuracy of
      myocardial perfusion single photon emission computed tomography (SPECT) for the
      detection and evaluation of patients with coronary artery disease. Attenuation
      artifacts, because of diaphragmatic attenuation, frequently affect the evaluation
      of the inferior wall, especially in male patients. PURPOSE: The aim of this study
      was to evaluate the value of AC for the assessment of infarct size in coronary
      artery disease patients after inferior myocardial infarction. MATERIALS AND
      METHODS: Gated-SPECT with Tc-labeled compounds with AC by hybrid SPECT/computed
      tomography (CT) was performed in 56 male patients with documented previous
      inferior myocardial infarction. Both corrected and uncorrected SPECT images were
      processed after motion and scatter correction by ordered-subset expectation
      maximization iterative reconstruction. When needed, a manual realignment between
      SPECT and computed tomography (CT) sections was performed. Uncorrected and
      corrected SPECT images were analyzed for perfusion using a 5-point segmental
      scoring scale from 0 (normal) to 4 (absent). Summed stress score (SSS), summed
      rest score (SRS), and summed difference score (SDS) of the inferior left
      ventricle wall (inferoseptal, inferior, infero-apical and infero-lateral
      segments) were determined and compared with the regional wall motion score as
      determined by uncorrected gated-SPECT. RESULTS: The SSS, SRS, SDS for attenuation
      uncorrected and attenuation-corrected studies were 14.02 +/- 7.9, 9.51 +/- 7, 4.5
      +/- 3.2 and 9.39 +/- 7.1, 5.6 +/- 6.1, 3.8 +/- 2.8, respectively. Differences
      were statistically significant (P<0.0001) for SSS and SRS but not for SDS. The
      regional summed rest score of the inferior wall (SRS of inferior segments) showed
      a better correlation with the regional summed wall motion score of the same
      segments: R2=0.50 in comparison to uncorrected SRS, R2=0.46. CONCLUSION: The
      combination of diaphragmatic attenuation and inferior myocardial infarction
      determines an artifactual overestimation of infarct size of inferior infarcts.
      The AC regional perfusion score (SRS) correlates with the regional wall motion
      score of the inferior wall. AC does not affect the detection and size of residual
      ischemia (SDS).

PMID- 21897309
TI  - Fully automated and reproducible radiosynthesis of high specific activity
      [11C]raclopride and [11C]Pittsburgh compound-B using the combination of two
      commercial synthesizers.
AB  - INTRODUCTION: The use of 11C-labeled radiotracers in routine positron emission
      tomography studies is dependent on the production capability of radiochemistry
      laboratories. Therefore, considerable efforts are being focused on the
      development of fast, efficient, and robust methods for the preparation of such
      radiotracers. METHODS: The fully automated syntheses of [11C]raclopride and
      [11C]Pittsburgh compound-B (PIB) starting from cyclotron-produced [11C]CH4 are
      reported. [11C]methyl iodide and [11C]methyl triflate were produced in the
      TRACERlab FXC Pro synthesis box. Methylation reactions and the final formulation
      were performed using the AutoLoop (captive solvent method) and the ReFORM-plus
      systems, respectively. RESULTS: [11C]raclopride (n=30) and [11C]PIB (n=24) were
      synthesized by O-[11C]-methylation and N-[11C]-methylation of (S)-O
      desmethylraclopride and 6-OH-BTA-0 using [11C]methyl iodide and [11C]methyl
      triflate, respectively. Good radiochemical yields (51.3 +/- 11.2 and 32.9 +/-
      6.6%, referred to as [11C]methyl iodide, decay corrected) and specific activities
      (109 +/- 20 and 143 +/- 26 GBq/umol) were obtained for [11C]raclopride and
      [11C]PIB, respectively, in a fully automated process. Radiochemical purity was
      higher than 99% in all cases. CONCLUSION: The fast, robust and fully automated
      processes reported here allow [11C]raclopride and [11C]PIB synthesis with good
      radiochemical yields and high specific activities. Consecutive productions can be
      performed with minimal intervention on the synthesis modules and minimal exposure
      to radiation.

PMID- 21897310
TI  - Obesity in pregnancy: deliver sensitive care.

PMID- 21897311
TI  - A pure act.

PMID- 21897312
TI  - Frequency of fetal heart rate categories and short-term neonatal outcome.
AB  - OBJECTIVE: To estimate the time spent in each fetal heart rate category during
      labor and during the last 2 hours before delivery in term singleton pregnancy and
      to estimate the relationship between the time spent in each category and short
      term neonatal outcomes. METHODS: This study reviewed fetal heart rate data and
      newborn outcomes of women in term labor in 10 hospitals over 28 months. Fetal
      heart rate characteristics were assessed by labor and delivery nurses, and
      categories were assigned by computer using definitions from the Eunice Kennedy
      Shriver National Institute of Child Health and Human Development. The duration of
      time in each category was calculated and correlated with newborn outcome.
      RESULTS: Forty-eight thousand four hundred forty-four patients were identified.
      Considering all of labor, category I was present 77.9% of the time, category II
      was present 22.1% of the time, and category III was present 0.004% of the time.
      In the last 2 hours before delivery, category I decreased to 60.9% of the
      duration, category II increased to 39.1%, and category III increased to 0.006%.
      Newborns of women whose last 2 hours were exclusively category I did well; only
      0.6% had 5-minute Apgar scores less than 7, and 0.2% had low Apgar scores with
      neonatal intensive care unit (NICU) admission. When more than 75% of the last 2
      hours was category II, low 5-minute Apgar score increased to 1.3% of patients,
      and low 5-minute Apgar score with NICU admission increased to 0.7% (both P<.001).
      CONCLUSION: Category I and category II fetal heart rate patterns are common in
      labor, and category III patterns are rare. Increasing time in category II in the
      last 2 hours of labor is associated with increased short-term newborn morbidity.
      LEVEL OF EVIDENCE: III.

PMID- 21897313
TI  - Pelvic floor disorders 5-10 years after vaginal or cesarean childbirth.
AB  - OBJECTIVE: To estimate differences in pelvic floor disorders by mode of delivery.
      METHODS: We recruited 1,011 women for a longitudinal cohort study 5-10 years
      after first delivery. Using hospital records, we classified each birth as:
      cesarean without labor, cesarean during active labor, cesarean after complete
      cervical dilation, spontaneous vaginal birth, or operative vaginal birth. At
      enrollment, stress incontinence, overactive bladder, anal incontinence, and
      prolapse symptoms were assessed with a validated questionnaire. Pelvic organ
      support was assessed using the Pelvic Organ Prolapse Quantification system.
      Logistic regression analysis was used to estimate the relative odds of each
      pelvic floor disorder by obstetric history, adjusting for relevant confounders.
      RESULTS: Compared with cesarean without labor, spontaneous vaginal birth was
      associated with a significantly greater odds of stress incontinence (odds ratio
      [OR] 2.9, 95% confidence interval [CI] 1.5-5.5) and prolapse to or beyond the
      hymen (OR 5.6, 95% CI 2.2-14.7). Operative vaginal birth significantly increased
      the odds for all pelvic floor disorders, especially prolapse (OR 7.5, 95% CI 2.7
      20.9). These results suggest that 6.8 additional operative births or 8.9
      spontaneous vaginal births, relative to cesarean births, would lead to one
      additional case of prolapse. Among women delivering exclusively by cesarean,
      neither active labor nor complete cervical dilation increased the odds for any
      pelvic floor disorder considered, although the study had less than 80% power to
      detect a doubling of the odds with these exposures. CONCLUSION: Although
      spontaneous vaginal delivery was significantly associated with stress
      incontinence and prolapse, the most dramatic risk was associated with operative
      vaginal birth. LEVEL OF EVIDENCE: II.

PMID- 21897314
TI  - The prevalence of tympanic membrane and related middle ear pathology in children:
      a large longitudinal cohort study followed from birth to age ten.
AB  - OBJECTIVE: To record with video-otoscopy the appearance of the tympanic membranes
      of a cross section of children aged 9 to 10 years. STUDY DESIGN: Cross-sectional
      study nested within an established longitudinal study of childhood development,
      the Avon Longitudinal Study of Parents and Children. SETTING: South West England,
      U.K. PARTICIPANTS: Approximately 6908 of 7261 children with ages ranging from 105
      to 140 months born between April 1, 1991, and December 31, 1992, were examined by
      trained technicians with video-otoscopy. MAIN OUTCOME MEASURES: Two photographs
      were taken of each child's tympanic membranes to show the features of the pars
      tensa and the pars flaccida. RESULTS: In just less than three quarters of the
      children, both ears were normal. Retraction of the pars flaccida was present in
      9.6% of children, and that of the pars tensa was present in 7.9%. Most of these
      changes were mild with few severe retractions. There were 15 cases of overt or
      suspected cholesteatoma. CONCLUSION: The tympanic membrane changes reflect most
      of the middle ear disease seen in 9- to 10-year-old children. The prevalence is
      low, and few children have serious disease at this stage.

PMID- 21897315
TI  - Treatment of the horizontal semicircular canal canalithiasis: pros and cons of
      the repositioning maneuvers in a clinical study and critical review of the
      literature.
AB  - OBJECTIVE: Several repositioning maneuvers have been proposed for the treatment
      of benign paroxysmal positional vertigo (BPPV) due to canalithiasis of the
      horizontal semicircular canal (HSC). However, comparisons between these canalith
      repositioning procedures as well as a generally accepted algorithm for the
      management of HSC canalithiasis are currently lacking. The aim of this study was
      to compare the efficacy of 3 different treatment proposals and review the
      relevant literature. STUDY DESIGN: Prospective clinical study. SETTING: Tertiary
      neurotology department. PATIENTS: Sixty patients diagnosed with HSC
      canalithiasis. INTERVENTIONS: A single application of Baloh's maneuver (n = 13),
      Vannucchi's forced prolonged position (n = 29), or Asprella-Gufoni maneuver (n =
      18). MAIN OUTCOME MEASURES: Bilateral geotropic nystagmus. RESULTS: The first
      application of the Baloh's maneuver seemed to be significantly less effective
      than both Vannucchi's forced prolonged position (p = 0.035) and the Asprella
      Gufoni maneuver (p = 0.006). No significant difference was detected in the
      efficiency of Vannucchi's forced prolonged position and the Asprella-Gufoni
      maneuver for this population (p = 0.4). CONCLUSION: The Asprella-Gufoni maneuver
      and Vannucchi's forced prolonged position both seem to be significantly more
      effective than the Baloh's maneuver in the treatment of HSC canalithiasis. The
      important pros of the Asprella-Gufoni maneuver versus Vannucchi's forced
      prolonged position are patient's convenience and maximal use of gravitational and
      angular acceleration forces. Controlled clinical studies are needed to conclude
      to an evidence-based proposal for the therapeutical steps that should be followed
      after the diagnosis of HSC canalithiasis.

PMID- 21897316
TI  - Relationship between postoperative aeration around the stapes and postoperative
      hearing outcome after canal wall down tympanoplasty with canal reconstruction for
      cholesteatoma.
AB  - OBJECTIVES: To evaluate the correlation between postoperative aeration around the
      stapes and hearing outcome after canal wall down tympanoplasty with canal
      reconstruction for cholesteatoma. STUDY DESIGN: Retrospective case review.
      SETTING: University hospital otolaryngology department. PATIENTS: Seventy ears of
      65 patients with middle ear cholesteatoma were included. Patients who had fixed
      or poorly mobile ossicular chain was excluded. INTERVENTIONS: They were underwent
      canal wall down tympanoplasty with canal reconstruction. Canal wall was
      reconstructed with the tragal or conchal cartilage and the cortical bone plate.
      MAIN OUTCOME MEASURES: We measured aeration around the stapes on coronal and
      axial computed tomographic sections at 1 year after ossiculoplasty and
      investigated the correlation between postoperative aeration around the stapes and
      postoperative air-bone gap (using the mean of 0.5-, 1-, and 2-kHz threshold
      values) at 1 year after ossiculoplasty. We also investigated it for each of
      Wullstein type and for each of 0.25-, 0.5-, 1-, 2-, and 4-kHz thresholds.
      RESULTS: Aeration around the stapes was negatively correlated with postoperative
      air-bone gap (correlation coefficient, -0.53; p < 0.05). Types I and IV
      tympanoplasty had a higher correlation with postoperative air-bone gap than type
      III tympanoplasty. The 0.5-KHz frequency had a higher correlation with
      postoperative air bone gap than other frequencies. CONCLUSION: Measurement of
      postoperative aeration around the stapes is an effective method for evaluating
      the importance of middle ear aeration. Aeration around the stapes contributes to
      better hearing outcome.

PMID- 21897317
TI  - High-frequency skull vibration-induced nystagmus test in partial vestibular
      lesions.
AB  - OBJECTIVES: To establish the effectiveness of the skull vibration-induced
      nystagmus test (SVINT) as a rapid high-frequency stimulation test, in the
      evaluation of partial unilateral vestibular lesions (pUVL). METHODS: SVINT (30,
      60, and 100 Hz), caloric, and head-shaking tests were performed in 99 patients
      with pUVL. These results were compared with those in 9 patients with symmetrical
      partial bilateral labyrinthine malformations, 131 patients with total unilateral
      vestibular lesions (tUVL), and 95 control subjects. RESULTS: A skull vibratory
      nystagmus (SVN) was found in 75% of patients with pUVL and 98% with tUVL. In
      pUVL: SVINT revealed asymmetric responses in 20% of patients where other tests
      were normal; SVN direction at 100 Hz was opposite to the head-shaking nystagmus
      direction in 30% and opposite to SVN at 30 Hz in 10% of cases. At 100 Hz, SVN
      beat toward the safe side in 91% of cases; SVN values at 60 and 100 Hz were
      higher than those at 30 Hz (p < 0.005). SVN was found in unilateral superior
      canal dehiscences. Partial bilateral labyrinthine malformations revealed no
      nystagmus. CONCLUSION: SVINT complements head-shaking and caloric tests in
      multifrequency assessment of patients with pUVL, as a global vestibular test. In
      contrast with tUVL results, SVINT does not always indicate the side of partial
      lesions, neither does it locate their level on the vestibulo-ocular pathway. This
      test is useful to reveal a vestibular asymmetry as a bedside examination test and
      may be used as a "vestibular Weber."

PMID- 21897318
TI  - Temporal bone findings in a case of Susac's syndrome.
AB  - OBJECTIVE: To describe the histopathologic findings in the temporal bones of a
      patient with Susac's syndrome (SS). BACKGROUND: The key clinical features of SS
      consist of symptoms of encephalopathy, visual defects due to occlusion of
      branches of the retinal artery, and sensorineural hearing loss. The otopathology
      in SS has not been described. MATERIALS AND METHODS: A 51-year-old woman was
      hospitalized with severe headache, rapidly progressive encephalopathy, and
      bilateral low-frequency sensorineural hearing loss. Magnetic resonance imaging
      showed lesions of the corpus callosum. Fluorescein angiography of the eyes showed
      focal areas of irregular retinal artery caliber and leakage from small vessels.
      SS was diagnosed. She died of a pulmonary embolus 1 month after onset of
      symptoms. Both temporal bones were prepared in celloidin and examined using light
      microscopy. RESULTS: Findings were nearly identical in both temporal bones. The
      apical halves of both cochleae showed widespread atrophy of structures of the
      cochlear duct (inner and outer hair cells, tectorial membranes, striae
      vasculares, spiral ligaments, and spiral limbi). The apical parts of both
      cochleae also showed apparent occlusion of capillaries within the stria
      vascularis and related areas of the cochlear duct. Cochlear neurons were present
      in normal numbers. There was no endolymphatic hydrops. The vestibular sense
      organs were normal for age. CONCLUSION: This first reported otopathologic case of
      SS with hearing loss showed atrophy and degeneration involving the apical halves
      of the cochlear duct without inflammation or infection. The findings were
      consistent with capillary occlusion as being responsible for the atrophy.

PMID- 21897319
TI  - Outcomes of facial nerve grafting in 155 cases: predictive value of history and
      preoperative function.
AB  - OBJECTIVE: To investigate the factors that were effectual on the recovery of the
      facial nerve functions after repair with grafting. STUDY DESIGN: Retrospective
      case review. SETTING: Private neuro-otologic and cranial base quaternary referral
      center. PATIENTS: One hundred ninety-four patients underwent facial nerve
      grafting during lateral cranial base surgery between July 1989 and December 2009.
      The mean age of the patients was 44.1 +/- 15.8 years (range, 2-79 yr). There were
      94 male and 100 female patients. Facial nerve functions were normal in 89
      patients, whereas facial nerve paresis or paralysis was present for a mean
      duration of 25.4 months (range, 1-600 mo) in the rest of the patients. MAIN
      OUTCOME MEASURE: Final facial nerve motor function. RESULTS: Best outcome, which
      was Grade III according to House-Brackmann scale, was achieved in 105 of 155
      patients with a follow-up of 1 year or longer (67.7%). Final result was grade IV
      in 23 (14.8%), grade V in 8 (5.2%), and grade VI in 19 patients (12.3%).
      Preoperative deficit duration was found to be the only significant factor that
      affected the prognosis (p = 0.027). Receiver operating characteristic curve
      analysis revealed that the most critical time for recovery to grades III and IV
      function is 6 months (p < 0.001). CONCLUSION: A number of factors were implicated
      to affect the success rate of facial nerve grafting, but only the duration of
      preoperative facial nerve deficit was found to be significant. Thus, timely
      management of facial nerve problems is critical for achieving optimal results.

PMID- 21897320
TI  - Treatment of the atretic ear with round window vibrant soundbridge implantation
      in infants and children: electrocochleography and audiologic outcomes.
AB  - OBJECTIVE: To evaluate the long-term outcomes of the first 5 infants and 9
      children with congenital aural atresia (CAA) who had undergone hearing
      rehabilitation using the MED-EL Vibrant Soundbridge with intraoperative
      assistance of electrocochleography (ECoG) for optimal fitting of the floating
      mass transducer (FMT) on the round window (RW) membrane. STUDY DESIGN: Tertiary
      referral medical center; retrospective case series. PATIENTS: Infants and
      children ranging in age from 2 months to 16 years with a moderate-to-severe
      conductive or mixed hearing loss with CAA. For comparison, the study population
      was divided into 2 groups: older children (>=5 yr of age; 5 patients) and younger
      children/infants (<5 yr of age; 9 subjects) who were submitted to different
      audiologic tests appropriate for their age and general condition. INTERVENTION:
      RW implantation. MAIN OUTCOME MEASURES: Compound action potential threshold and
      amplitude were assessed as a function of different methods for stabilizing the
      FMT on the RW. Pure tone audiogram at 0.5, 1, 2, and 4 kHz, free-field speech
      testing (older children), bone conduction and free-field auditory brainstem
      response (ABR; younger children and infants), intraoperative and postoperative
      complications, and FMT displacement or extrusion rate. RESULTS: Statistically
      significant differences were observed with ECoG recordings between pre- and post
      FMT-RW membrane optimization with fascia and cartilage (p < 0.001). Significant
      improvements were observed in speech perception and pure-tone and ABR threshold,
      immediately after surgery and at follow-up intervals (12-65 mo) in children and
      infants (p < 0.01). No complications or instances of device extrusion were
      observed. CONCLUSION: Infants and children with moderate-to-severe conductive or
      mixed hearing loss, not suitable or unwilling to accept Bone-Anchored Hearing
      Aids and who would not tolerate traditional bone and air conduction hearing aids,
      obtain substantial benefit with the FMT-RW implantation procedure. Intraoperative
      ECoG is of significant help in achieving the best FMT-RW fitting.

PMID- 21897321
TI  - Usefulness of cone-beam computed tomography in determining the position of
      ossicular prostheses: a cadaveric model.
AB  - HYPOTHESIS: Cone-beam computed tomography (CT) is proving useful in various
      operative settings. We hypothesize that it has great potential as an
      intraoperative assessment tool for ossicular prosthesis positioning. BACKGROUND:
      Results from prosthetic ossiculoplasty are frequently disappointing. Undetected
      intraoperative displacement of the prosthesis may be caused, and obscured, by
      placement of an overlying cartilage graft. METHODS: A cadaveric right temporal
      bone was prepared with a tympanomeatal flap, and an extended posterior
      tympanotomy through a cortical mastoidectomy. Each of 3 commercially available
      prostheses was positioned in 3 different locations: (1) optimal, (2) grossly
      displaced, and (3) marginally displaced. The intended prosthetic positions were
      confirmed by endoscopy before and after cone-beam CT image acquisition. The
      primary outcome measure was the position of the prosthesis in relation to the
      stapes and tympanic membrane, as assessed by 5 expert reviewers blinded to the
      study. Secondary outcome measures included optimal dosing for adequate image
      resolution and radiographic scatter associated with different prosthetic
      materials. RESULTS: Cone-beam CT accurately demonstrated the position of
      ossicular reconstruction prostheses with respect to the stapes and tympanic
      membrane. Prosthesis displacement, whether minimally or marked, was also
      accurately demonstrated. Interobserver agreement among the 5 reviewers, measured
      using a Fleiss kappa statistic, ranged from 0.4 to 0.8 (fair to substantial
      agreement depending on type and position of the prosthesis). CONCLUSION: Cone
      beam CT is a useful tool for determining the position of ossicular reconstruction
      prostheses in situ. We suggest it has potential for intraoperative assessment, to
      check positioning after the prosthesis has been covered with a cartilage graft
      and tympanomeatal flap.

PMID- 21897322
TI  - Hyperventilation-induced nystagmus and vertigo after stereotactic radiotherapy
      for vestibular schwannoma.
AB  - OBJECTIVE: To describe the phenomenon of hyperventilation-induced nystagmus (HVN)
      after stereotactic radiotherapy for vestibular schwannoma. PATIENTS: We present 2
      patients with vestibular schwannoma and no pretreatment vestibular symptoms who
      both received stereotactic radiotherapy. Within 2 months of completing treatment,
      both patients developed intense vertigo while exerting themselves. Video
      oculography demonstrated an intense nystagmus with the fast phase directed toward
      the side of the schwannoma in both patients. INTERVENTION: Diagnostic. RESULTS:
      Patients who have undergone surgical resection of their vestibular schwannoma, or
      have a large tumor, will often demonstrate HVN with the fast phase directed away
      from the side of the tumor. This is distinct from patients with smaller lesions
      who have a fast-phase nystagmus toward the tumor's side. This second type of
      nystagmus is thought to originate from changes in the extracellular calcium
      concentration secondary to hyperventilation-induced alkalosis. CONCLUSION: We
      hypothesize that stereotactic radiotherapy induced greater demyelination of the
      vestibular nerve leading to the observable sign of HVN. These patients represent
      the first reported cases of HVN after stereotactic radiation and illustrate the
      pathophysiology of HVN, which may lead to a greater understanding of the effects
      of stereotactic radiotherapy.

PMID- 21897323
TI  - Disorders affecting the fourth ventricle: etiology and clinical correlates.
AB  - OBJECTIVE: The fourth ventricle encompasses many vital structures including the
      brainstem as its floor and the cerebellum as its lateral wall and roof.
      Therefore, lesions affecting the fourth ventricle may present as cerebellar or
      brainstem manifestations. Herein, we presented our experience in the diagnosis of
      disorders affecting the fourth ventricle during the past 15 years. STUDY DESIGN:
      Retrospective study. SETTING: University hospital. SUBJECTS: From September 1995
      to August 2010, 24,838 patients with vertigo/dizziness visited the clinic. Of
      them, 13 patients (0.5%) had tumor/stroke affecting the fourth ventricle. MAIN
      OUTCOME MEASURES: All patients underwent a battery of audiovestibular function
      test. RESULTS: All patients had vertigo (100%) and then ataxia (92%) and
      nausea/vomiting (85%). Eight patients (68%) displayed persistent nystagmus. Most
      (>75%) patients showed central signs in electronystagmographic recordings and
      abnormal caloric coupled with visual suppression test. Three patients underwent
      both ocular and cervical vestibular-evoked myogenic potential tests, and abnormal
      results were noted in all 3 patients indicating a brainstem involvement. However,
      magnetic resonance imaging failed to demonstrate brainstem lesion in these 3
      patients. Final diagnoses consisted of the following: cavernoma, n = 3;
      metastatic cancer, n = 3; astrocytoma, n = 2; meningioma, n = 2; epidermoid cyst,
      n = 1; ependymoma, n = 1; and lymphoma, n = 1. The prognosis was poor as 10
      patients (77%) died within 2 years. CONCLUSION: When a vertiginous patient
      displayed ataxia, persistent vomiting, and persistent nystagmus, lesion affecting
      the fourth ventricle should be kept in mind because its prognosis is poor.
      Abnormal results in electronystagmography and in ocular and cervical vestibular
      evoked myogenic potentials may serve as a supplementary to magnetic resonance
      imaging to delineate the involvement of the lesion.

PMID- 21897324
TI  - A paradigm shift in salvage surgery for radiated vestibular schwannoma.
AB  - OBJECTIVE: Determine whether more conservative management for surgical salvage
      after failed radiation leads to better facial nerve outcomes. STUDY DESIGN:
      "Retrospective" review using prospectively planned database. SETTING: Private
      practice, tertiary neurotology/neurosurgery referral center. PATIENTS: A series
      of 73 patients with vestibular schwannoma, who underwent primary radiosurgery
      with no other intervention and then surgical salvage tumor removal using the
      translabyrinthine approach. INTERVENTION(S): Translabyrinthine craniotomy for
      vestibular schwannoma salvage surgery after failed radiation, with either gross
      total or partial tumor removal. MAIN OUTCOME MEASURES: Long-term (1 yr) House
      Brackmann (H-B) facial nerve grade and change in facial nerve grade from before
      to after surgery. RESULTS: Of the 73 patients, 79.5% had gross total removal,
      5.5% had planned partial resection (subtotal or near total), and 15.1% had
      intraoperatively elected partial removal with most of these being near total
      removal. At 1 year of follow-up, good facial nerve function (H-B I/II) was found
      in 50% of patients with gross total removal and 85.7% of those with partial
      removal (p <= 0.03). The H-B grade was maintained postoperatively in 45.8% and
      78.6% of the 2 groups, respectively (p <= 0.037), with 21.7% of the total removal
      group having unsatisfactory outcomes (H-B V or VI) compared with 7.1% of patients
      with partial removal. To date, no patient has required additional treatment.
      CONCLUSION: Failed radiosurgery is an increasing indication for salvage surgery
      in patients with posterior fossa tumors. A conservative approach with a
      willingness to perform partial and near-total tumor removals leads to better
      facial nerve outcomes with no current evidence of treatment compromise.

PMID- 21897325
TI  - Pleomorphic adenoma of the external auditory canal: recurrence of a parotid gland
      primary.

PMID- 21897326
TI  - Cartilage cap occlusion technique for dehiscent superior semicircular canals.
AB  - OBJECTIVE: Assessment of a cartilage cap occlusion of dehiscent superior
      semicircular canals via a transmastoid and tegmen mini-craniotomy approach
      surgical technique. STUDY DESIGN: Retrospective case review. SETTING: Tertiary
      referral center. PATIENTS: Thirty-seven patients over a 2 year time period
      underwent cartilage cap occlusion of a dehiscent superior semicircular canal.
      INTERVENTION: Therapeutic. MAIN OUTCOME MEASURE: Subjective improvement and/or
      resolution of dizziness postoperatively. RESULTS: Of 37 patients, 29 (78%) felt
      much better and had resolution of their dizziness. Of 37 patients, 5 (14%) felt
      some definite improvement, although not complete resolution. Two patients (5%)
      felt their dizziness was neither better nor worse, and 1 patient (3%) felt
      dizziness was worse after surgery. CONCLUSION: The cartilage cap occlusion
      technique of dehiscent superior semicircular canals via a transmastoid and tegmen
      mini-craniotomy approach is a good option for managing symptomatic patients with
      a dehiscent superior semicircular canal.

PMID- 21897327
TI  - Ocular vestibular evoked myogenic potentials in response to air-conducted sound
      in Meniere's disease.
AB  - BACKGROUND: Currently, Meniere's disease is predominantly diagnosed through
      clinical criteria. Additional standard vestibular testing, such as
      nystagmography, can show variable responses. In the last decade, the cervical
      vestibular evoked myogenic potential (VEMP) has shown to be of additive value in
      diagnosing Meniere's disease. In this study, the results of the ocular VEMP
      (oVEMP) in response to air-conducted sound will be discussed. OBJECTIVES: To
      evaluate possible changes of the oVEMP in a large group (n = 37) of patients with
      Meniere's disease. MATERIAL AND METHODS: In 55 subjects without Meniere's disease
      and 37 patients with Meniere's disease, oVEMPs in response to air-conducted sound
      stimulation (tone-burst, 500 Hz; maximum stimulus level, 120 dB sound pressure
      level) were studied. Recording was performed in upgaze with surface electrodes
      underneath both eyes. The burden of the test was scored by all subjects on a
      visual analogue scale. RESULTS: In patients with Meniere's disease the response
      rates are lower, the oVEMP amplitudes are smaller, and thresholds are higher than
      in subjects without Meniere's disease. This effect is observed in both ears of
      patients with Meniere's disease. The affected ear is more altered than the
      clinically unaffected ear. CONCLUSION: The air-conducted oVEMP can be a relevant
      addition to the current diagnostic workup of patients with possible Meniere's
      disease. A lower response rate, smaller amplitude, and higher threshold of the
      oVEMP indicate the pathologic disease in this population.

PMID- 21897328
TI  - Regenerative treatment for tympanic membrane perforation.
AB  - OBJECTIVE: To establish a tissue engineering therapy for the treatment of large
      tympanic membrane perforation (TMP) without the need for conventional surgical
      therapy. STUDY DESIGN: Randomized control trial. SETTING: General hospital.
      PATIENTS AND METHODS: A total of 63 chronic TMPs were randomly selected from
      outpatients. INTERVENTION: Of the total 63 chronic TMPs, 53 were randomly
      assigned to the basic fibroblast growth factor (b-FGF) group and the remaining 10
      were randomly assigned to the control group. Materials used for the TM repair
      were gelatin sponge and fibrin glue with/without b-FGF. After creating a
      mechanical disruption of the edge of the TMP, a gelatin sponge was immersed in b
      FGF or saline (for the control group) and placed over the perforation. Fibrin
      glue was dripped over the sponge as a sealant. MAIN OUTCOME MEASURES: The
      effectiveness of this therapy was evaluated by closure rates, hearing level, and
      sequelae 3 weeks after treatment. The treatment was repeated up to 4 times for
      cases in which complete closure of the TMP was not achieved after 1 round of
      treatment. RESULTS: Complete closure of the TMP was achieved in more than 98.1%
      (52/53) of the patients in the b-FGF group and 10% (1/10) of the patients in the
      control group. The average hearing level of all patients with successful TM
      repair was improved. Serious sequelae were not observed in any patient.
      CONCLUSION: This study demonstrates that a combination of gelatin sponge, b-FGF,
      and fibrin glue enables the regeneration of the TM without conventional operative
      procedures. This innovative regenerative therapy is an easy, safe, cost
      effective, and minimally invasive outpatient treatment.

PMID- 21897329
TI  - Cellular therapy to treat haematological and other malignancies: progress and
      pitfalls.
AB  - The recent Food and Drug Administration (FDA) approval of a cellular therapy to
      treat castration resistant prostate cancer has reinforced the potential of
      cellular therapy to consolidate current pharmacological approaches to treating
      cancer. The emergence of the cell manufacturing facility to facilitate clinical
      translation of these new methodologies allows greater access to these novel
      therapies. Here we review different strategies currently being explored to treat
      haematological malignancies with a focus on adoptive allogeneic or autologous
      transfer of antigen specific T cells, NK cells or dendritic cells. These
      approaches all aim to generate immunological responses against overexpressed
      tissue antigens, mismatched minor histocompatability antigens or tumour
      associated antigens. Current successes and limitations of these different
      approaches will be discussed with an emphasis on challenges encountered in
      generating long term engraftment, antigen selection and implementation as well as
      therapeutic immune monitoring of clinical responses, with examples from recent
      clinical trials.

PMID- 21897330
TI  - Regulation of cellular therapy in Australia.
AB  - Use of cellular products for therapeutic purposes has predominantly been
      unregulated in Australia until recently. Transplant of haemopoietic progenitor
      cells (HPC) for bone marrow regeneration is now a routine treatment for many
      disorders with an established mechanism of facility accreditation. However, other
      cellular therapies do not have any form of accreditation, are not well evaluated
      and may be associated with significant risks. On 31 May 2011 the Therapeutic
      Goods Administration (TGA) implemented a long heralded regulatory biologicals
      framework for cell and tissue based therapies. The framework currently excludes
      human HPC, organs for direct transplantation and reproductive materials which are
      already covered by various forms of existing peer review and accreditation. This
      new framework is a practical approach for applying regulation based on the risk
      of the product to the recipient with four classes of product. Class 1 is reserved
      for the least regulated products and currently does not contain any proposed
      products. Class 2 will be for minimally manipulated products which will only
      require manufacturing compliance and evaluation against product and other
      mandatory standards before entry onto the Australian Register of Therapeutic
      Goods (ARTG). Class 3 and 4 products will be more than minimally manipulated and
      these cells and tissues may be used in a non-homologous manner. Class 3 and 4
      products will represent a spectrum of risk where Class 4 therapies will represent
      the highest potential risk to the recipient, with the same requirements for Class
      2 approvals but with additional requirements for comprehensive evaluation of a
      dossier for quality, safety and efficacy of the product. The extent of this
      quality, safety and efficacy data will depend upon the nature of the product and
      its associated risks, but will be more comprehensive for Class 4 as opposed to
      Class 3 products. The only truly contentious feature of this framework is the
      extremely high cost for dossier evaluation and the puzzling absence of an orphan
      drug scheme for biologicals.

PMID- 21897331
TI  - Gene therapy: therapeutic applications and relevance to pathology.
AB  - This review discusses gene therapy as a new treatment paradigm where genetic
      material is introduced into cells for therapeutic benefit. The genetic material
      is the 'drug'. It can have a transient or ongoing effect depending on whether or
      not the introduced genetic material becomes part of the host cell DNA. Different
      delivery and gene technologies are chosen by investigators to maximise gene
      delivery to, and expression within, the target cells appropriate for the disease
      indication. The presence and expression of the introduced genetic material is
      monitored by molecular means so that treatment efficacy can be assessed via
      changes in surrogate and/or actual markers of disease. Of interest to the
      pathologist will be the approaches being developed for the disease indications
      highlighted and the monitoring of treatment efficacy.

PMID- 21897332
TI  - Cellular therapy in the Asia-Pacific region. A guide for the future pathologist.
AB  - The Asia-Pacific region includes a large number of countries offering a broad
      range and quality of healthcare services. Almost every country in the region
      offers at least some cellular therapies, from the highly regulated countries like
      Japan, Korea and Australia, through to countries where the oversight is less
      formal. The key healthcare drivers for this sector are the ageing population,
      obesity epidemic, organ donation statistics and the emergence of personalised
      medicine. This is a rapidly advancing field with breakthroughs announced
      regularly. The Asia-Pacific region is poised to become a world leader in the
      provision of this new generation of therapeutic options in a safe and
      standardised manner.

PMID- 21897334
TI  - Valproic acid increases susceptibility to endotoxin shock through enhanced
      release of high-mobility group box 1.
AB  - High-mobility group box 1 (HMGB1) is a nuclear factor and a secreted protein.
      During inflammation, HMGB1 is secreted into the extracellular space where it can
      interact with the receptor for advanced glycation end products and trigger
      proinflammatory signals. Extracellular HMGB1 plays a critical role in several
      inflammatory diseases such as sepsis and rheumatoid arthritis. Valproic acid
      (VPA) is one of the most frequently prescribed antiepileptic drugs. The present
      study was undertaken to investigate the effect of VPA on secretion of HMGB1 in
      systemic inflammatory responses induced by lipopolysaccharide. Pretreatment with
      VPA increased the susceptibility of mice to lipopolysaccharide in endotoxemia.
      Valproic acid induced HMGB1 release and nuclear factor kappaB activation in RAW
      blue cells. Valproic acid promoted the phosphorylation of ERK1/2 but not that of
      p38 or JNK. The MEK1/2 inhibitor PD98059 also suppressed HMGB1 release and
      activation of nuclear factor kappaB induced by VPA. Valproic acid induced
      expression of gamma-aminobutyric acid receptors in macrophages, and picrotoxin, a
      gamma-aminobutyric acid A receptor antagonist, inhibited the VPA-activated
      phosphorylation of ERK and VPA-induced HMGB1 release. These results suggest that
      VPA may exacerbate innate immune responses to endotoxin through enhanced release
      of HMGB1.

PMID- 21897335
TI  - Activated protein C restores hepatic microcirculation during sepsis by modulating
      vasoregulator expression.
AB  - Activated protein C (aPC) promotes fibrinolysis while inhibiting coagulation and
      inflammation. In septic patients, aPC levels are depleted, and aPC treatment has
      emerged as a therapeutic option. To better understand the mechanism(s) by which
      aPC improves survival in sepsis, we sought to determine the effect of aPC
      treatment on hepatic vasoactive gene and protein expression, leading to changes
      in hepatic vascular responsiveness in a septic animal model. Under anesthesia,
      rats underwent sham or cecal ligation and puncture followed by aPC treatment (1
      mg/kg, twice daily, i.v.). Treatment with aPC significantly decreased hepatic
      endothelin 1 (ET-1)/ET A receptor mRNA and protein expression. To determine the
      effect of aPC on hepatic microvasculature, ET-1-induced changes in liver
      microcirculation were assessed by intravital microscopy. This approach
      demonstrated aPC significantly improved hepatic perfusion index in the animals
      that underwent cecal ligation and puncture in the absence of significant changes
      in portal venous pressure. Furthermore, although aPC did not affect ET-1
      dependent sinusoidal vasoconstriction, aPC induced hepatoprotective effects via
      enhanced red blood cell velocity. Collectively, these data demonstrate aPC
      ameliorates ET-1-dependent changes in hepatic microcirculation and improves
      hepatic function in the setting of sepsis.

PMID- 21897336
TI  - The influence of experimental alcohol load and alcohol intoxication on S100B
      concentrations.
AB  - Because nearly 50% of patients with mild head trauma are alcohol intoxicated, it
      often remains unclear if the neurological deficits are due to alcohol
      intoxication or to intracerebral damage. To avoid unnecessary head computed
      tomography investigations in patients with mild head trauma, S100B is currently
      used as an exclusion marker for cellular brain damage. However, whether S100B
      levels are influenced by alcohol itself remains to be unclear. Therefore, we
      performed a case-control study of nontraumatized, alcohol-intoxicated patients to
      prove if serum S100B is altered by alcohol uptake. Furthermore, we investigated
      if alcohol infusions combined with an initial oral alcohol load up to a blood
      alcohol steady state of 100 mg/dL affected S100B levels in healthy volunteers (n
      = 12). In this standardized experimental procedure, no significant increase in
      S100B levels could be found. In contrast, compared with the control group (n = 60
      sober and healthy), the ethyl alcohol-intoxicated patients (n = 61; mean ethyl
      alcohol, 251 [SD, 87] mg/dL) had higher S100B concentrations (0.193 [SD, 0.45]
      vs. 0.063 [SD, 0.059] MUg/L; P < 0.001), and 39% of them had levels greater than
      the pathologic cutoff at greater than 0.104 MUg/L. However, no significant
      correlation was found between ethyl alcohol concentrations and S100B within the
      respective group. Our clinical data suggest that blood alcohol concentrations far
      in excess of 100 mg/dL are associated with increased S100B levels in alcohol
      intoxicated patients.

PMID- 21897333
TI  - Genes linked to energy metabolism and immunoregulatory mechanisms are associated
      with subcutaneous adipose tissue distribution in HIV-infected men.
AB  - OBJECTIVE: Genetic studies may help explain abnormalities of fat distribution in
      HIV-infected patients treated with antiretroviral therapy (ARV). METHODS:
      Subcutaneous adipose tissue (SAT) volume measured by MRI in the leg, the lower
      trunk, the upper trunk, and the arm was examined in 192 HIV-infected White men,
      ARV-treated from the Fat Redistribution and Metabolic Change in HIV infection
      study. Single-nucleotide polymorphisms were assayed using the Illumina Human
      CNV370-quad beadchip. Multivariate and univariate genome-wide association
      analyses of the four SAT depots were implemented in PLINK software adjusted for
      age and ARV duration. Functional annotation analysis using Ingenuity Systems
      Pathway Analysis tool was carried out for markers with P lower than 10(-3) near
      known genes identified by multivariate analysis. RESULTS: Loci (rs10504906,
      rs13267998, rs921231) in or near the anion exchanger solute carrier family 26,
      member 7 isoform a (SLC26A7) were strongly associated with the upper trunk and
      the arm SAT (9.8*10(-7) <=P<7.8*10(-6)). Loci (rs193139, rs7523050, rs1761621) in
      and near a gene-rich region including G-protein-signaling modulator 2 (GPSM2) and
      syntaxin-binding protein 3 (STXBP3) were significantly associated with the lower
      body SAT depots (9.9*10(-7) <=P<9.5*10(-6)). GPSM2 is associated with cell
      division and cancer whereas STXBP3 is associated with glucose metabolism in
      adipoctyes. Ingenuity Systems Pathway Analysis identified atherosclerosis,
      mitochondrial function, and T-cell-mediated apoptosis as processes related to SAT
      volume in HIV-infected individuals (P<5*10(-3)). CONCLUSION: Our results are
      limited by the small sample size and replication is needed; however, this genomic
      scan uncovered new genes associated with metabolism and inflammatory pathways
      that may affect SAT volume in ARV-treated HIV-infected patients.

PMID- 21897337
TI  - Total plasma sulfide as a marker of shock severity in nonsurgical adult patients.
AB  - Previous animal and human studies have suggested that total plasma sulfide plays
      a role in the pathophysiology of shock. This study's aim was to determine the
      value of total plasma sulfide as a marker of shock severity in nonsurgical adult
      patients admitted to the ICU. Forty-one patients, with various types of shock
      (septic, cardiogenic, obstructive, and hypovolemic), were included in the study,
      with an average total plasma sulfide concentration of 23.2 +/- 26.3 uM. Survivors
      (of shock) had lower total plasma sulfide concentrations than nonsurvivors (13.0
      +/- 26.3 vs. 31.9 +/- 31.5 uM; P = 0.02). Total plasma sulfide correlated with
      dose of administered norepinephrine (R linear = 0.829; P = 0.001) and with Acute
      Physiology and Chronic Health Evaluation II (APACHE II) score (R cubic = 0.767; P
      = 0.001). Area under the receiver operating characteristic for total plasma
      sulfide as a predictor of ICU mortality was 0.739 (confidence interval, 0.587
      0.892; P = 0.009). Even after correcting for APACHE II score and lactate values,
      total plasma sulfide correlated with mortality (odds ratio, 1.058; 95% confidence
      interval, 1.001-1.118; P = 0.045). The study provides evidence that, in
      nonsurgical adult ICU patients admitted because of any type of shock, total
      plasma sulfide correlates with administered norepinephrine dose at admission,
      severity of disease (APACHE II score >=30 points), and survival outcome.

PMID- 21897338
TI  - Nebulized anticoagulants limit coagulopathy but not inflammation in pseudomonas
      aeruginosa-induced pneumonia in rats.
AB  - Disturbed alveolar fibrin turnover is a characteristic feature of pneumonia.
      Inhibitors of coagulation could exert lung-protective effects via anticoagulant
      (inhibiting fibrin deposition) and possibly anti-inflammatory pathways, but could
      also affect host defense. In this randomized controlled in vivo laboratory study,
      rats were challenged intratracheally with Pseudomonas aeruginosa, inducing
      pneumonia, and randomized to local treatment with normal saline (placebo),
      recombinant human activated protein C (rh-APC), plasma-derived antithrombin (AT),
      heparin, or danaparoid. Induction of P. aeruginosa pneumonia resulted in
      activation of pulmonary coagulation and inhibition of pulmonary fibrinolysis, as
      reflected by increased pulmonary levels of thrombin-AT complexes and fibrin
      degradation products and decreased pulmonary levels plasminogen activator
      activity. Pseudomonas aeruginosa pneumonia was accompanied by systemic
      coagulopathy, since systemic levels of thrombin-AT complexes increased, and
      systemic levels of plasminogen activator activity decreased. Although rh-APC and
      plasma-derived AT potently limited pulmonary coagulopathy, neither heparin nor
      danaparoid affected net pulmonary fibrin turnover. Recombinant human APC also
      displayed systemic anticoagulant effects. Neither bacterial clearance nor
      pulmonary inflammation was affected by anticoagulant therapy. Nebulization of rh
      APC or plasma-derived AT attenuated pulmonary coagulopathy, but not bacterial
      clearance or inflammation, in a rat model of P. aeruginosa pneumonia.

PMID- 21897339
TI  - Longitudinal associations between physical load and chronic low back pain in the
      general population: the Doetinchem Cohort Study.
AB  - STUDY DESIGN: Prospective cohort study. OBJECTIVE: We explored long-term
      associations between physical load exposure and chronic low back pain (LBP) using
      data from an ongoing population-based cohort study. SUMMARY OF BACKGROUND DATA:
      Physical load in work or daily life is often studied in relation to LBP. Most
      studies are cross-sectional or have a limited follow-up. METHODS: Between 1993
      and 2007, 4738 men and women aged 25 to 64 years were measured maximal 3 times
      with 5-year intervals. Physical load in daily activities (9 items, e.g., awkward
      postures, mechanical vibration) was assessed by questionnaire at 2 measurements
      and chronic LBP 3 times. Physical load exposure at both measurements was
      described. Multivariable logistic regression analyses were adjusted for sex, age,
      education, work status, body mass index, physical activity, and smoking. RESULTS:
      Despite stable prevalence rates of physical load exposure, about 50% of the
      participants exposed changed their exposure during a 5-year period. 7.2% of the
      participants reported awkward postures at 2 measurements, 8.4% at the first
      measurement only, and 6.8% at the second measurement only. Among all physical
      load variables, associations with chronic LBP were found only for awkward
      postures. An increased risk for incident chronic LBP was found in participants
      exposed twice to awkward postures. In contrast, only single exposure to awkward
      postures was associated with persistence of chronic LBP. CONCLUSION: Awkward
      postures were associated with chronic LBP in the general population. Exposure to
      awkward postures at 2 measurements with 5 years in between did increase the risk
      for incident chronic LBP, but not for persistence of chronic LBP.

PMID- 21897340
TI  - Phraseology of disc herniation: an inevitable revision: passing the posterior
      disc prolapse--retrolapse is superior.

PMID- 21897341
TI  - Support of concept that migrating progenitor cells from stem cell niches
      contribute to normal regeneration of the adult mammal intervertebral disc: a
      descriptive study in the New Zealand white rabbit.
AB  - STUDY DESIGN: Descriptive experimental study performed in rabbits of 2 age
      groups. OBJECTIVE: To study and investigate presence of prechondrocytic cells and
      cell migration routes (MR) in the intervertebral disc (IVD) region to gain
      knowledge about the normal IVD regeneration pattern. SUMMARY OF BACKGROUND DATA:
      Disc degeneration is thought to play a major role in patients with chronic lumbar
      pain. Regeneration processes and cell migration within the IVD have been sparsely
      described. Therefore, it is of interest to increase knowledge of these processes
      in order to understand pathological conditions of the IVD. METHODS: At the
      beginning of the experiment, 5-bromo-2-deoxyuridine (BrdU) in vivo labeling was
      performed in 2 groups of rabbits, 3 and 9 months old (total 27 rabbits). BrdU is
      incorporated into DNA during mitosis, and then it is gradually diluted with each
      cell division until it finally disappears. Incorporation of BrdU was then
      visualized by immunohistochemistry (IHC) at different time points providing cell
      division pattern and presence of slow-cycling cells in the IVD region. IVD tissue
      was investigated by IHC for growth and differentiation factor-5 (GDF5), SOX9
      (chondrogenic lineage markers), SNAIL homolog 1 (SNAI1), SNAIL homolog 2 (SLUG)
      (migration markers), and beta1-INTEGRIN (cellular adhesion marker). In addition,
      GDF5, SOX9, and BMPRIB expression were investigated on genetic level. RESULTS:
      BrdU cells were observed in early time points in the IVD niche, adjacent to the
      epiphyseal plate, at later time points mainly in outer region of the annulus
      fibrosus for both age groups of rabbits, indicating a gradual migration of cells.
      The presence of SLUG, SNAI1, GDF5, SOX9, and beta1-INTEGRIN was found in same
      regions. CONCLUSION: The results suggest a cellular MR from the IVD stem cell
      niche toward the annulus fibrosus and the inner parts of the IVD. These findings
      may be of importance for understanding IVD regenerative mechanisms and for future
      development of biological treatment strategies.

PMID- 21897343
TI  - A randomized, controlled, double-blind trial of fluoroscopic caudal epidural
      injections in the treatment of lumbar disc herniation and radiculitis.
AB  - STUDY DESIGN: A randomized, controlled, double-blind trial. OBJECTIVE: To assess
      the effectiveness of fluoroscopically directed caudal epidural injections in
      managing chronic low back and lower extremity pain in patients with disc
      herniation and radiculitis with local anesthetic with or without steroids.
      SUMMARY OF BACKGROUND DATA: The available literature on the effectiveness of
      epidural injections in managing chronic low back pain secondary to disc
      herniation is highly variable. METHODS: One hundred twenty patients suffering
      with low back and lower extremity pain with disc herniation and radiculitis were
      randomized to one of the two groups: group I received caudal epidural injections
      with an injection of local anesthetic, lidocaine 0.5%, 10 mL; group II patients
      received caudal epidural injections with 0.5% lidocaine, 9 mL, mixed with 1 mL of
      steroid. The Numeric Rating Scale (NRS), the Oswestry Disability Index 2.0 (ODI),
      employment status, and opioid intake were utilized with assessment at 3, 6, and
      12 months posttreatment. RESULTS: The percentage of patients with significant
      pain relief of 50% or greater and/or improvement in functional status with 50% or
      more reduction in ODI scores was seen in 70% and 67% in group I and 77% and 75%
      in group II with average procedures per year of 3.8 +/- 1.4 in group I and 3.6 +
      1.1 in group II. However, the relief with first and second procedures was
      significantly higher in the steroid group. The number of injections performed was
      also higher in local anesthetic group even though overall relief was without any
      significant difference among the groups. There was no difference among the
      patients receiving steroids. CONCLUSION: Caudal epidural injection with local
      anesthetic with or without steroids might be effective in patients with disc
      herniation or radiculitis. The present evidence illustrates potential superiority
      of steroids compared with local anesthetic at 1-year follow-up.

PMID- 21897345
TI  - Reliability of clinical measurement for assessing spinal fusion: an experimental
      sheep study.
AB  - STUDY DESIGN: A sheep study designed to compare the accuracy of static
      radiographs, dynamic radiographs, and computed tomographic (CT) scans for the
      assessment of thoracolumbar facet joint fusion as determined by micro-CT
      scanning. OBJECTIVE: To determine the accuracy and reliability of conventional
      imaging techniques in identifying the status of thoracolumbar (T13-L1) facet
      joint fusion in a sheep model. SUMMARY OF BACKGROUND DATA: Plain radiographs are
      commonly used to determine the integrity of surgical arthrodesis of the
      thoracolumbar spine. Many previous studies of fusion success have relied solely
      on postoperative assessment of plain radiographs, a technique lacking sensitivity
      for pseudarthrosis. CT may be a more reliable technique, but is less well
      characterized. METHODS: Eleven adult sheep were randomized to either attempted
      arthrodesis using autogenous bone graft and internal fixation (n = 3) or
      intentional pseudarthrosis (IP) using oxidized cellulose and internal fixation (n
      = 8). After 6 months, facet joint fusion was assessed by independent observers,
      using (1) plain static radiography alone, (2) additional dynamic radiographs, and
      (3) additional reconstructed spiral CT imaging. These assessments were correlated
      with high-resolution micro-CT imaging to predict the utility of the conventional
      imaging techniques in the estimation of fusion success. RESULTS: The capacity of
      plain radiography alone to correctly predict fusion or pseudarthrosis was 43% and
      was not improved using plain radiography and dynamic radiography with also a 43%
      accuracy. Adding assessment by reformatted CT imaging to the plain radiography
      techniques increased the capacity to predict fusion outcome to 86% correctly. The
      sensitivity, specificity, and accuracy of static radiography were 0.33, 0.55, and
      0.43, respectively, those of dynamic radiography were 0.46, 0.40, and 0.43,
      respectively, and those of radiography plus CT were 0.88, 0.85, and 0.86,
      respectively. CONCLUSION: CT-based evaluation correlated most closely with high
      resolution micro-CT imaging. Neither plain static nor dynamic radiographs were
      able to predict fusion outcome accurately.

PMID- 21897344
TI  - Oxiplex reduces leg pain, back pain, and associated symptoms after lumbar
      discectomy.
AB  - STUDY DESIGN: Prospective, randomized, blinded clinical trial. OBJECTIVE: To
      evaluate effectiveness of Oxiplex gel for reduction of pain and associated
      symptoms after lumbar discectomy. SUMMARY OF BACKGROUND DATA: Oxiplex gel
      (carboxymethylcellulose, polyethylene oxide, and calcium) is used during
      discectomy to coat the surgical site for reduction of pain and symptoms after
      lumbar discectomy. METHODS: Patients undergoing single-level lumbar discectomy
      performed by laminectomy or laminotomy and randomized to receive either surgery
      plus Oxiplex gel (treatment group) or surgery alone (control group) were assessed
      6 months after surgery using (1) a quality of life questionnaire (Lumbar Spine
      Outcomes Questionnaire [LSOQ]) and (2) clinical evaluations. RESULTS: There were
      no statistically significant differences in baseline demographics, surgical
      procedures, LSOQ scores, and clinical evaluations between treatment (N = 177) and
      control (N = 175) groups. More gel-treated patients were satisfied with outcome
      of their surgical treatment than control patients (P = 0.05). The gel-treated
      group showed greater reductions in pain and symptoms from baseline compared with
      surgery-only controls. Additional benefits of gel were consistently shown in
      reduction of leg and back pain at 6 months in the patient population having
      substantial back pain at baseline (greater than or equal to the median LSOQ pain
      score of 63). In that population, there was a statistically significant reduction
      of leg pain and back pain (P < 0.01) in the treatment group compared with
      controls. Fewer patients in the treatment group had abnormal musculoskeletal
      physical examinations at 6 months compared with controls. There were no cases of
      cerebrospinal fluid leaks and no differences in laboratory values or vital signs.
      Patients in the treatment group had less hypoesthesia, paraesthesia, sensory
      loss, and fewer reoperations during the 6-month follow-up than controls (1 vs.
      6). CONCLUSION: These data demonstrate improvements in clinical outcomes
      resulting from the use of Oxiplex gel in discectomy procedures for treatment of
      lumbar disc herniation.

PMID- 21897346
TI  - Fusion versus nonoperative management for chronic low back pain: do comorbid
      diseases or general health factors affect outcome?
AB  - STUDY DESIGN: Systematic review of literature focused on heterogeneity of
      treatment effect analysis. OBJECTIVE: The objectives of this systematic review
      were to determine if comorbid disease and general health factors modify the
      effect of fusion versus nonoperative management in chronic low back pain (CLBP)
      patients? SUMMARY OF BACKGROUND DATA: Surgical fusion as a treatment of back pain
      continues to be controversial due to inconsistent responses to treatment. The
      reasons for this are multifactorial but may include heterogeneity in the patient
      population and in surgeon's attitudes and approaches to this complex problem.
      There is a relative paucity of high quality publications from which to draw
      conclusions. We were interested in investigating the possibility of detecting
      treatment response differences comparing fusion to conservative management for
      CLBP among subpopulations with different disease specific and general health risk
      factors. METHODS: A systematic search was conducted in MEDLINE and the Cochrane
      Collaboration Library for literature published from 1990 through December 2010.
      To evaluate whether the effects of CLBP treatment varied by disease or general
      health subgroups, we sought randomized controlled trials or nonrandomized
      observational studies with concurrent controls evaluating surgical fusion versus
      nonoperative management for CLBP. Of the original 127 citations identified, only
      5 reported treatment effects (fusion vs. conservative management) separately by
      disease and general health subgroups of interest. Of those, only two focused on
      patients who had primarily back pain without spinal stenosis or
      spondylolisthesis. RESULTS: Few studies comparing fusion to nonoperative
      management reported differences in outcome by specific disease or general health
      subpopulations. Among those that did, we observed the effect of fusion compared
      to nonoperative management was slightly more favorable in patients with no
      additional comorbidities compared with those with additional comorbidities and
      more marked in nonsmokers compared with smokers. CONCLUSION: It is unclear from
      the literature which patients are the best candidates for fusion versus
      conservative management when experiencing CLBP without significant neurological
      impairment. Nonsmokers may be more likely to have a favorable surgical fusion
      outcome in CLBP patients. Comorbid disease presence has not been shown to
      definitively modify the effect of fusion. Further prospective studies that are
      designed to evaluate these and other subgroup effects are encouraged to confirm
      these findings. CLINICAL RECOMMENDATIONS: We recommend optimizing the management
      of medical co-morbidities and smoking cessation before considering surgical
      fusion in CLBP patients. Strength of recommendation: Weak.

PMID- 21897347
TI  - Evaluating the correlation and responsiveness of patient-reported pain with
      function and quality-of-life outcomes after spine surgery.
AB  - STUDY DESIGN: Systematic review. OBJECTIVE: To determine the correlation of
      patient-reported pain with physical function and health-related quality of life
      (HRQoL) after spine surgery and to determine the responsiveness of pain, physical
      function, and HRQoL after spine surgery. SUMMARY OF BACKGROUND DATA: Several
      validated outcome instruments are available to assess the success of treatment
      for chronic low back pain. These patient-centered tools include measurements for
      pain based on numeric scales, validated condition-specific functional outcomes
      measures, and HRQoL outcomes measures. It is unclear whether these three types of
      patient-reported outcomes are measuring different constructs and whether all
      three should be measured after spine surgery. In addition, it is unclear which of
      these outcomes measures is most sensitive to change after spine surgery for low
      back pain. METHODS: A systematic search was conducted in MEDLINE, EMBASE, and the
      Cochrane Collaboration Library for literature published through December 2010.
      The correlation between pain (visual analog scale, VAS), physical function
      (Oswestry Disability Index, ODI), and HRQoL (36-Item Short Form Health Survey [SF
      36] and European Quality of Life [EQ-5D]) change scores was performed using the
      Spearman rank correlation coefficients. To compare the responsiveness of pain,
      function, and HRQoL scores after spine surgery, we calculated effect sizes by
      dividing change scores by the SD of the baseline scores. This standardized method
      allowed us to compare the responsiveness of each outcome measure directly and
      reported an effect size of 0.2 to 0.3 as a "small" effect, around 0.5 a "medium"
      effect and 0.8 to infinity, a "large" effect. To determine whether the
      differences in effect sizes measuring responsiveness were significantly
      different, we conducted a Wilcoxon signed-rank test between each of the three
      measurements of pain, function, and HRQoL scores when there was enough data to
      perform the test. RESULTS: None of the correlations exceeded 0.70 using the
      Spearman rank correlation coefficients, suggesting that these outcomes are
      measuring different constructs. The strongest correlations were between the VAS
      back pain change scores and the SF-36 physical composite score change scores (rho
      = 0.67) and VAS back pain change scores and ODI change scores (rho = 0.69). The
      pooled mean effect sizes for the five studies that reported a pain measure and
      the ODI were 1.4 +/- 0.57 and 1.1 +/- 0.39, respectively. Both are considered
      "large" effect sizes. The pooled mean effect sizes for the three studies
      reporting the SF-36 physical and mental composite scores were 0.66 +/- 0.39 and
      0.54 +/- 0.36, respectively. Both are considered "medium" effect sizes. The
      pooled mean effect sizes for the single studies reporting the EQ-5D and SF-36
      total score were 0.78 +/- 0.12 and 0.34 +/- 0.21. These were "medium" and
      "small," respectively. CONCLUSION: We observed little correlation between the
      change in pain and the change in HRQoL outcomes measures. The strongest
      correlation was between VAS pain and ODI but was still not considered strong
      (0.69). These findings suggest that these three outcomes (pain, function, and
      HRQoL) are measuring different constructs. With respect to responsiveness, VAS
      pain and ODI were the only outcomes measures that demonstrated a large effect
      after lumbar spine surgery. None of the HRQoL tools were as sensitive to the
      treatment. The EQ-5D, SF physical composite, and SF mental composite outcomes
      demonstrated a medium effect, while the SF-36 total score demonstrated a small
      effect. The responsive measure shows that the more specific the outcomes tool,
      the more sensitive the response. CLINICAL RECOMMENDATIONS: Recommendation 1: When
      surgically treating CLBP, we recommend administering both a VAS for pain and a
      condition-specific physical measure such as the ODI before and after surgical
      intervention as these outcomes are the most treatment specific and responsive to
      change. Strength of recommendation: Strong.Recommendation 2: When evaluating the
      surgical outcomes for CLBP in the clinical-research setting, we recommend
      selecting a shorter version for measuring general HRQoL (e.g., SF-12, EQ-5D) to
      minimize clinician and patient burden. Strength of recommendation: Strong.

PMID- 21897348
TI  - Ticagrelor (Brilinta)--better than clopidogrel (Plavix)?
AB  - The FDA has approved ticagrelor (Brilinta-AstraZeneca), an oral antiplatelet
      drug, for use with low-dose aspirin to reduce the rate of thrombotic
      cardiovascular events in patients with acute coronary syndrome (ACS). It will
      compete with clopidogrel (Plavix) and prasugrel (Effient) for such use.
      Clopidogrel is expected to become available generically in the US within the next
      few months.

PMID- 21897349
TI  - Gabapentin encarbil (Horizant) for restless leg syndrome.
AB  - Gabapentin enacarbil (Horizant-GlaxoSmithKline), a new extended-release (ER)
      tablet formulation of gabapentin, has been approved by the FDA for treatment of
      moderate-to-severe restless legs syndrome (RLS). The immediate-release (IR)
      formulation of gabapentin (Neurontin,and others), which is approved for treatment
      of epilepsy and postherpetic neuralgia, has been used for many years to treat
      RLS. Another ER tablet formulation of gabapentin (Gralise) has been approved by
      the FDA for treatment of postherpetic neuralgia.

PMID- 21897350
TI  - Screening for melanoma.

PMID- 21897351
TI  - Biochemical measurement of neonatal hypoxia.
AB  - Neonatal hypoxia ischemia is characterized by inadequate blood perfusion of a
      tissue or a systemic lack of oxygen. This condition is thought to
      cause/exacerbate well documented neonatal disorders including neurological
      impairment. Decreased adenosine triphosphate production occurs due to a lack of
      oxidative phosphorylation. To compensate for this energy deprived state molecules
      containing high energy phosphate bonds are degraded. This leads to increased
      levels of adenosine which is subsequently degraded to inosine, hypoxanthine,
      xanthine, and finally to uric acid. The final two steps in this degradation
      process are performed by xanthine oxidoreductase. This enzyme exists in the form
      of xanthine dehydrogenase under normoxic conditions but is converted to xanthine
      oxidase (XO) under hypoxia-reperfusion circumstances. Unlike xanthine
      dehydrogenase, XO generates hydrogen peroxide as a byproduct of purine
      degradation. This hydrogen peroxide in combination with other reactive oxygen
      species (ROS) produced during hypoxia, oxidizes uric acid to form allantoin and
      reacts with lipid membranes to generate malondialdehyde (MDA). Most mammals,
      humans exempted, possess the enzyme uricase, which converts uric acid to
      allantoin. In humans, however, allantoin can only be formed by ROS-mediated
      oxidation of uric acid. Because of this, allantoin is considered to be a marker
      of oxidative stress in humans, but not in the mammals that have uricase. We
      describe methods employing high pressure liquid chromatography (HPLC) and gas
      chromatography mass spectrometry (GCMS) to measure biochemical markers of
      neonatal hypoxia ischemia. Human blood is used for most tests. Animal blood may
      also be used while recognizing the potential for uricase-generated allantoin.
      Purine metabolites were linked to hypoxia as early as 1963 and the reliability of
      hypoxanthine, xanthine, and uric acid as biochemical indicators of neonatal
      hypoxia was validated by several investigators. The HPLC method used for the
      quantification of purine compounds is fast, reliable, and reproducible. The GC/MS
      method used for the quantification of allantoin, a relatively new marker of
      oxidative stress, was adapted from Gruber et al. This method avoids certain
      artifacts and requires low volumes of sample. Methods used for synthesis of MMDA
      were described elsewhere. GC/MS based quantification of MDA was adapted from
      Paroni et al. and Cighetti et al. Xanthine oxidase activity was measured by HPLC
      by quantifying the conversion of pterin to isoxanthopterin. This approach proved
      to be sufficiently sensitive and reproducible.

PMID- 21897352
TI  - Time-lapse microscopy of early embryogenesis in Caenorhabditis elegans.
AB  - Caenorhabditis elegans has often been used as a model system in studies of early
      developmental processes. The transparency of the embryos, the genetic resources,
      and the relative ease of transformation are qualities that make C. elegans an
      excellent model for early embryogenesis. Laser-based confocal microscopy and
      fluorescently labeled tags allow researchers to follow specific cellular
      structures and proteins in the developing embryo. For example, one can follow
      specific organelles, such as lysosomes or mitochondria, using fluorescently
      labeled dyes. These dyes can be delivered to the early embryo by means of
      microinjection into the adult gonad. Also, the localization of specific proteins
      can be followed using fluorescent protein tags. Examples are presented here
      demonstrating the use of a fluorescent lysosomal dye as well as fluorescently
      tagged histone and ubiquitin proteins. The labeled histone is used to visualize
      the DNA and thus identify the stage of the cell cycle. GFP-tagged ubiquitin
      reveals the dynamics of ubiquitinated vesicles in the early embryo. Observations
      of labeled lysosomes and GFP:: ubiquitin can be used to determine if there is
      colocalization between ubiquitinated vesicles and lysosomes. A technique for the
      microinjection of the lysosomal dye is presented. Techniques for generating
      transgenenic strains are presented elsewhere. For imaging, embryos are cut out of
      adult hermaphrodite nematodes and mounted onto 2% agarose pads followed by time
      lapse microscopy on a standard laser scanning confocal microscope or a spinning
      disk confocal microscope. This methodology provides for the high resolution
      visualization of early embryogenesis.

PMID- 21897353
TI  - Brain imaging investigation of the neural correlates of emotional
      autobiographical recollection.
AB  - Recollection of emotional autobiographical memories (AMs) is important to healthy
      cognitive and affective functioning--remembering positive AMs is associated with
      increased personal well-being and self-esteem, whereas remembering and ruminating
      on negative AMs may lead to affective disorders. Although significant progress
      has been made in understanding the brain mechanisms underlying AM retrieval in
      general, less is known about the effect of emotion on the subjective re
      experience of AMs and the associated neural correlates. This is in part due to
      the fact that, unlike the investigations of the emotion effect on memory for
      laboratory-based microevents, often times AM studies do not have a clear focus on
      the emotional aspects of remembering personal events. Here, we present a protocol
      that allows investigation of the neural correlates of recollecting emotional AMs
      using functional magnetic resonance imaging (fMRI). Cues for these memories are
      collected prior to scanning by means of an autobiographical memory questionnaire
      (AMQ), therefore allowing for proper selection of emotional AMs based on their
      phenomenological properties (i.e., intensity, vividness, personal significance).
      This protocol can be used in healthy and clinical populations alike.

PMID- 21897354
TI  - Brain imaging investigation of the neural correlates of emotion regulation.
AB  - The ability to control/regulate emotions is an important coping mechanism in the
      face of emotionally stressful situations. Although significant progress has been
      made in understanding conscious/deliberate emotion regulation (ER), less is known
      about non-conscious/automatic ER and the associated neural correlates. This is in
      part due to the problems inherent in the unitary concepts of automatic and
      conscious processing. Here, we present a protocol that allows investigation of
      the neural correlates of both deliberate and automatic ER using functional
      magnetic resonance imaging (fMRI). This protocol allows new avenues of inquiry
      into various aspects of ER. For instance, the experimental design allows
      manipulation of the goal to regulate emotion (conscious vs. non-conscious), as
      well as the intensity of the emotional challenge (high vs. low). Moreover, it
      allows investigation of both immediate (emotion perception) and long-term effects
      (emotional memory) of ER strategies on emotion processing. Therefore, this
      protocol may contribute to better understanding of the neural mechanisms of
      emotion regulation in healthy behaviour, and to gaining insight into possible
      causes of deficits in depression and anxiety disorders in which emotion
      dysregulation is often among the core debilitating features.

PMID- 21897355
TI  - Preparation of adult Drosophila eyes for thin sectioning and microscopic
      analysis.
AB  - Drosophila has long been used as model system to study development, mainly due to
      the ease with which it is genetically tractable. Over the years, a plethora of
      mutant strains and technical tricks have been developed to allow sophisticated
      questions to be asked and answered in a reasonable amount of time. Fundamental
      insight into the interplay of components of all known major signaling pathways
      has been obtained in forward and reverse genetic Drosophila studies. The fly eye
      has proven to be exceptionally well suited for mutational analysis, since, under
      laboratory conditions, flies can survive without functional eyes. Furthermore,
      the surface of the insect eye is composed of some 800 individual unit eyes
      (facets or ommatidia) that form a regular, smooth surface when looked at under a
      dissecting microscope. Thus, it is easy to see whether a mutation might affect
      eye development or growth by externally looking for the loss of the smooth
      surface ('rough eye' phenotype; Fig. 1) or overall eye size, respectively (for
      examples of screens based on external eye morphology see e.g.). Subsequent
      detailed analyses of eye phenotypes require fixation, plastic embedding and thin
      sectioning of adult eyes. The Drosophila eye develops from the so-called eye
      imaginal disc, a bag of epithelial cells that proliferate and differentiate
      during larval and pupal stages (for review see e.g.). Each ommatidium consists of
      20 cells, including eight photoreceptors (PR or R-cells; Fig. 2), four lens
      secreting cone cells, pigment cells ('hexagon' around R-cell cluster) and a
      bristle. The photoreceptors of each ommatidium, most easily identified by their
      light sensitive organelles, the rhabdomeres, are organized in a trapezoid made up
      of the six "outer" (R1-6) and two "inner" photoreceptors (R7/8; R8 [Fig. 2] is
      underneath R7 and thus only seen in sections from deeper areas of the eye). The
      trapezoid of each facet is precisely aligned with those of its neighbors and the
      overall anteroposterior and dorsoventral axes of the eye (Fig. 3A). In
      particular, the ommatidia of the dorsal and ventral (black and red arrows,
      respectively) halves of the eye are mirror images of each other and correspond to
      two chiral forms established during planar cell polarity signaling (for review
      see e.g.). The method to generate semi-thin eye sections (such as those presented
      in Fig. 3) described here is slightly modified from the one originally described
      by Tomlinson and Ready. It allows the morphological analysis of all cells except
      for the transparent cone cells. In addition, the pigment of R-cells (blue
      arrowheads in Fig. 2 and 3) can be used as a cell-autonomous marker for the
      genotype of a R-cell, thus genetic requirements of genes in a subset of R-cells
      can readily be determined.

PMID- 21897356
TI  - Micro-mechanical characterization of lung tissue using atomic force microscopy.
AB  - Matrix stiffness strongly influences growth, differentiation and function of
      adherent cells. On the macro scale the stiffness of tissues and organs within the
      human body span several orders of magnitude. Much less is known about how
      stiffness varies spatially within tissues, and what the scope and spatial scale
      of stiffness changes are in disease processes that result in tissue remodeling.
      To better understand how changes in matrix stiffness contribute to cellular
      physiology in health and disease, measurements of tissue stiffness obtained at a
      spatial scale relevant to resident cells are needed. This is particularly true
      for the lung, a highly compliant and elastic tissue in which matrix remodeling is
      a prominent feature in diseases such as asthma, emphysema, hypertension and
      fibrosis. To characterize the local mechanical environment of lung parenchyma at
      a spatial scale relevant to resident cells, we have developed methods to directly
      measure the local elastic properties of fresh murine lung tissue using atomic
      force microscopy (AFM) microindentation. With appropriate choice of AFM indentor,
      cantilever, and indentation depth, these methods allow measurements of local
      tissue shear modulus in parallel with phase contrast and fluorescence imaging of
      the region of interest. Systematic sampling of tissue strips provides maps of
      tissue mechanical properties that reveal local spatial variations in shear
      modulus. Correlations between mechanical properties and underlying anatomical and
      pathological features illustrate how stiffness varies with matrix deposition in
      fibrosis. These methods can be extended to other soft tissues and disease
      processes to reveal how local tissue mechanical properties vary across space and
      disease progression.

PMID- 21897357
TI  - Dissection of the adult zebrafish kidney.
AB  - Researchers working in the burgeoning field of adult stem cell biology seek to
      understand the signals that regulate the behavior and function of stem cells
      during normal homeostasis and disease states. The understanding of adult stem
      cells has broad reaching implications for the future of regenerative medicine.
      For example, better knowledge about adult stem cell biology can facilitate the
      design of therapeutic strategies in which organs are triggered to heal themselves
      or even the creation of methods for growing organs in vitro that can be
      transplanted into humans. The zebrafish has become a powerful animal model for
      the study of vertebrate cell biology. There has been extensive documentation and
      analysis of embryonic development in the zebrafish. Only recently have scientists
      sought to document adult anatomy and surgical dissection techniques, as there has
      been a progressive movement within the zebrafish community to broaden the
      applications of this research organism to adult studies. For example, there are
      expanding interests in using zebrafish to investigate the biology of adult stem
      cell populations and make sophisticated adult models of diseases such as cancer.
      Historically, isolation of the zebrafish adult kidney has been instrumental for
      studying hematopoiesis, as the kidney is the anatomical location of blood cell
      production in fish. The kidney is composed of nephron functional units found in
      arborized arrangements, surrounded by hematopoietic tissue that is dispersed
      throughout the intervening spaces. The hematopoietic component consists of
      hematopoietic stem cells (HSCs) and their progeny that inhabit the kidney until
      they terminally differentiate. In addition, it is now appreciated that a group of
      renal stem/progenitor cells (RPCs) also inhabit the zebrafish kidney organ and
      enable both kidney regeneration and growth, as observed in other fish species. In
      light of this new discovery, the zebrafish kidney is one organ that houses the
      location of two exciting opportunities for adult stem cell biology studies. It is
      clear that many outstanding questions could be well served with this experimental
      system. To encourage expansion of this field, it is beneficial to document
      detailed methods of visualizing and then isolating the adult zebrafish kidney
      organ. This protocol details our procedure for dissection of the adult kidney
      from both unfixed and fixed animals. Dissection of the kidney organ can be used
      to isolate and characterize hematopoietic and renal stem cells and their
      offspring using established techniques such as histology, fluorescence activated
      cell sorting (FACS), expression profiling, and transplantation. We hope that
      dissemination of this protocol will provide researchers with the knowledge to
      implement broader use of zebrafish studies that ultimately can be translated for
      human application.

PMID- 21897358
TI  - Laser ablation of the zebrafish pronephros to study renal epithelial
      regeneration.
AB  - Acute kidney injury (AKI) is characterized by high mortality rates from
      deterioration of renal function over a period of hours or days that culminates in
      renal failure. AKI can be caused by a number of factors including ischemia, drug
      based toxicity, or obstructive injury. This results in an inability to maintain
      fluid and electrolyte homeostasis. While AKI has been observed for decades,
      effective clinical therapies have yet to be developed. Intriguingly, some
      patients with AKI recover renal functions over time, a mysterious phenomenon that
      has been only rudimentally characterized. Research using mammalian models of AKI
      has shown that ischemic or nephrotoxin-injured kidneys experience epithelial cell
      death in nephron tubules, the functional units of the kidney that are made up of
      a series of specialized regions (segments) of epithelial cell types. Within
      nephrons, epithelial cell death is highest in proximal tubule cells. There is
      evidence that suggests cell destruction is followed by dedifferentiation,
      proliferation, and migration of surrounding epithelial cells, which can
      regenerate the nephron entirely. However, there are many unanswered questions
      about the mechanisms of renal epithelial regeneration, ranging from the signals
      that modulate these events to reasons for the wide variation of abilities among
      humans to regenerate injured kidneys. The larval zebrafish provides an excellent
      model to study kidney epithelial regeneration as its pronephric kidney is
      comprised of nephrons that are conserved with higher vertebrates including
      mammals. The nephrons of zebrafish larvae can be visualized with fluorescence
      techniques because of the relative transparency of the young zebrafish. This
      provides a unique opportunity to image cell and molecular changes in real-time,
      in contrast to mammalian models where nephrons are inaccessible because the
      kidneys are structurally complex systems internalized within the animal. Recent
      studies have employed the aminoglycoside gentamicin as a toxic causative agent
      for study of AKI and subsequent renal failure: gentamicin and other antibiotics
      have been shown to cause AKI in humans, and researchers have formulated methods
      to use this agent to trigger kidney damage in zebrafish. However, the effects of
      aminoglycoside toxicity in zebrafish larvae are catastrophic and lethal, which
      presents a difficulty when studying epithelial regeneration and function over
      time. Our method presents the use of targeted cell ablation as a novel tool for
      the study of epithelial injury in zebrafish. Laser ablation gives researchers the
      ability to induce cell death in a limited population of cells. Varying areas of
      cells can be targeted based on morphological location, function, or even
      expression of a particular cellular phenotype. Thus, laser ablation will increase
      the specificity of what researchers can study, and can be a powerful new approach
      to shed light on the mechanisms of renal epithelial regeneration. This protocol
      can be broadly applied to target cell populations in other organs in the
      zebrafish embryo to study injury and regeneration in any number of contexts of
      interest.

PMID- 21897359
TI  - Normothermic cardiac arrest and cardiopulmonary resuscitation: a mouse model of
      ischemia-reperfusion injury.
AB  - Acute Kidney Injury (AKI) is a common, highly lethal, complication of critical
      illness which has a high mortality and which is most frequently caused by whole
      body hypoperfusion. Successful reproduction of whole-body hypoperfusion in rodent
      models has been fraught with difficulty. Models which employ focal ischemia have
      repeatedly demonstrated results which do not translate to the clinical setting,
      and larger animal models which allow for whole body hypoperfusion lack access to
      the full toolset of genetic manipulation possible in the mouse. However, in
      recent years a mouse model of cardiac arrest and cardiopulmonary resuscitation
      has emerged which can be adapted to model AKI. This model reliably reproduces
      physiologic, functional, anatomic, and histologic outcomes seen in clinical AKI,
      is rapidly repeatable, and offers all of the significant advantages of a murine
      surgical model, including access to genetic manipulative techniques, low cost
      relative to large animals, and ease of use. Our group has developed extensive
      experience with use of this model to assess a number of organ-specific outcomes
      in AKI.

PMID- 21897360
TI  - Examining the characteristics of episodic memory using event-related potentials
      in patients with Alzheimer's disease.
AB  - Our laboratory uses event-related EEG potentials (ERPs) to understand and support
      behavioral investigations of episodic memory in patients with amnestic mild
      cognitive impairment (aMCI) and Alzheimer's disease (AD). Whereas behavioral data
      inform us about the patients' performance, ERPs allow us to record discrete
      changes in brain activity. Further, ERPs can give us insight into the onset,
      duration, and interaction of independent cognitive processes associated with
      memory retrieval. In patient populations, these types of studies are used to
      examine which aspects of memory are impaired and which remain relatively intact
      compared to a control population. The methodology for collecting ERP data from a
      vulnerable patient population while these participants perform a recognition
      memory task is reviewed. This protocol includes participant preparation, quality
      assurance, data acquisition, and data analysis. In addition to basic setup and
      acquisition, we will also demonstrate localization techniques to obtain greater
      spatial resolution and source localization using high-density (128 channel)
      electrode arrays.

PMID- 21897361
TI  - ReAsH/FlAsH labeling and image analysis of tetracysteine sensor proteins in
      cells.
AB  - Fluorescent proteins and dyes are essential tools for the study of protein
      trafficking, localization and function in cells. While fluorescent proteins such
      as green fluorescence protein (GFP) have been extensively used as fusion partners
      to proteins to track the properties of a protein of interest, recent developments
      with smaller tags enable new functionalities of proteins to be examined in cells
      such as conformational change and protein-association. One small tag system
      involves a tetracysteine motif (CCXXCC) genetically inserted into a target
      protein, which binds to biarsenical dyes, ReAsH (red fluorescent) and FlAsH
      (green fluorescent), with high specificity even in live cells. The TC/biarsenical
      dye system offers far less steric constraints to the host protein than
      fluorescent proteins which has enabled several new approaches to measure
      conformational change and protein-protein interactions. We recently developed a
      novel application of TC tags as sensors of oligomerization in cells expressing
      mutant huntingtin, which when mutated aggregates in neurons in Huntington
      disease. Huntingtin was tagged with two fluorescent dyes, one a fluorescent
      protein to track protein location, and the second a TC tag which only binds
      biarsenical dyes in monomers. Hence, changes in colocalization between protein
      and biarsenical dye reactivity enabled submicroscopic oligomer content to be
      spatially mapped within cells. Here, we describe how to label TC-tagged proteins
      fused to a fluorescent protein (Cherry, GFP or CFP) with FlAsH or ReAsH in live
      mammalian cells and how to quantify the two color fluorescence (Cherry/FlAsH,
      CFP/FlAsH or GFP/ReAsH combinations).

PMID- 21897362
TI  - Pharmacological and functional genetic assays to manipulate regeneration of the
      planarian Dugesia japonica.
AB  - Free-living planarian flatworms have a long history of experimental usage owing
      to their remarkable regenerative abilities. Small fragments excised from these
      animals reform the original body plan following regeneration of missing body
      structures. For example if a 'trunk' fragment is cut from an intact worm, a new
      'head' will regenerate anteriorly and a 'tail' will regenerate posteriorly
      restoring the original 'head-to-tail' polarity of body structures prior to
      amputation. Regeneration is driven by planarian stem cells, known as 'neoblasts'
      which differentiate into ~30 different cell types during normal body homeostasis
      and enforced tissue regeneration. This regenerative process is robust and easy to
      demonstrate. Owing to the dedication of several pioneering labs, many tools and
      functional genetic methods have now been optimized for this model system.
      Consequently, considerable recent progress has been made in understanding and
      manipulating the molecular events underpinning planarian developmental
      plasticity. The planarian model system will be of interest to a broad range of
      scientists. For neuroscientists, the model affords the opportunity to study the
      regeneration of an entire nervous system, rather than simply the regrowth/repair
      of single nerve cell process that typically are the focus of study in many
      established models. Planarians express a plethora of neurotransmitters, represent
      an important system for studying evolution of the central nervous system and have
      behavioral screening potential. Regenerative outcomes are amenable to
      manipulation by pharmacological and genetic apparoaches. For example, drugs can
      be screened for effects on regeneration simply by placing body fragments in drug
      containing solutions at different time points after amputation. The role of
      individual genes can be studied using knockdown methods (in vivo RNAi), which can
      be achieved either through cycles of microinjection or by feeding bacterially
      expressed dsRNA constructs. Both approaches can produce visually striking
      phenotypes at high penetrance--for example, regeneration of bipolar animals. To
      facilitate adoption of this model and implementation of such methods, we showcase
      in this video article protocols for pharmacological and genetic assays (in vivo
      RNAi by feeding) using the planarian Dugesia japonica.

PMID- 21897363
TI  - Epigenetic silencing of the oncogenic miR-17-92 cluster during PU.1-directed
      macrophage differentiation.
AB  - The oncogenic cluster miR-17-92 encodes seven related microRNAs that regulate
      cell proliferation, apoptosis and development. Expression of miR-17-92 cluster is
      decreased upon cell differentiation. Here, we report a novel mechanism of the
      regulation of miR-17-92 cluster. Using transgenic PU.1(-/-) myeloid progenitors
      we show that upon macrophage differentiation, the transcription factor PU.1
      induces the secondary determinant Egr2 which, in turn, directly represses miR-17
      92 expression by recruiting histone demethylase Jarid1b leading to histone H3
      lysine K4 demethylation within the CpG island at the miR-17-92 promoter.
      Conversely, Egr2 itself is targeted by miR-17-92, indicating existence of mutual
      regulatory relationship between miR-17-92 and Egr2. Furthermore, restoring EGR2
      levels in primary acute myeloid leukaemia blasts expressing elevated levels of
      miR-17-92 and low levels of PU.1 and EGR2 leads to downregulation of miR-17-92
      and restored expression of its targets p21CIP1 and BIM. We propose that upon
      macrophage differentiation PU.1 represses the miR-17-92 cluster promoter by an
      Egr-2/Jarid1b-mediated H3K4 demethylation mechanism whose deregulation may
      contribute to leukaemic states.

PMID- 21897364
TI  - Temporal orchestration of circadian autophagy rhythm by C/EBPbeta.
AB  - Temporal organization of tissue metabolism is important for maintaining nutrient
      and energy homeostasis in mammals. Autophagy is a conserved cellular pathway that
      is activated in response to nutrient limitation, resulting in the degradation of
      cytoplasmic components and the release of amino acids and other nutrients. Here,
      we show that autophagy exhibits robust circadian rhythm in mouse liver, which is
      accompanied by cyclic induction of genes involved in various steps of autophagy.
      Functional analyses of transcription factors and cofactors identified C/EBPbeta
      as a potent activator of autophagy. C/EBPbeta is rhythmically expressed in the
      liver and is regulated by both circadian and nutritional signals. In cultured
      primary hepatocytes, C/EBPbeta stimulates the program of autophagy gene
      expression and is sufficient to activate autophagic protein degradation.
      Adenoviral-mediated RNAi knockdown of C/EBPbeta in vivo abolishes diurnal
      autophagy rhythm in the liver. Further, circadian regulation of C/EBPbeta and
      autophagy is disrupted in mice lacking a functional liver clock. We have thus
      identified C/EBPbeta as a key factor that links autophagy to biological clock and
      maintains nutrient homeostasis throughout light/dark cycles.

PMID- 21897365
TI  - Transcription factor Dlx2 protects from TGFbeta-induced cell-cycle arrest and
      apoptosis.
AB  - Acquiring resistance against transforming growth factor beta (TGFbeta)-induced
      growth inhibition at early stages of carcinogenesis and shifting to TGFbeta's
      tumour-promoting functions at later stages is a pre-requisite for malignant
      tumour progression and metastasis. We have identified the transcription factor
      distal-less homeobox 2 (Dlx2) to exert critical functions during this switch.
      Dlx2 counteracts TGFbeta-induced cell-cycle arrest and apoptosis in mammary
      epithelial cells by at least two molecular mechanisms: Dlx2 acts as a direct
      transcriptional repressor of TGFbeta receptor II (TGFbetaRII) gene expression and
      reduces canonical, Smad-dependent TGFbeta signalling and expression of the cell
      cycle inhibitor p21(CIP1) and increases expression of the mitogenic transcription
      factor c-Myc. On the other hand, Dlx2 directly induces the expression of the
      epidermal growth factor (EGF) family member betacellulin, which promotes cell
      survival by stimulating EGF receptor signalling. Finally, Dlx2 expression
      supports experimental tumour growth and metastasis of B16 melanoma cells and
      correlates with tumour malignancy in a variety of human cancer types. These
      results establish Dlx2 as one critical player in shifting TGFbeta from its tumour
      suppressive to its tumour-promoting functions.

PMID- 21897367
TI  - Starting from scratch: de novo kinetochore assembly in vertebrates.

PMID- 21897366
TI  - Obesity resistance and increased hepatic expression of catabolism-related mRNAs
      in Cnot3+/- mice.
AB  - Obesity is a life-threatening factor and is often associated with dysregulation
      of gene expression. Here, we show that the CNOT3 subunit of the CCR4-NOT
      deadenylase complex is critical to metabolic regulation. Cnot3(+/-) mice are lean
      with hepatic and adipose tissues containing reduced levels of lipids, and show
      increased metabolic rates and enhanced glucose tolerance. Cnot3(+/-) mice remain
      lean and sensitive to insulin even on a high-fat diet. Furthermore, introduction
      of Cnot3 haplodeficiency in ob/ob mice ameliorated the obese phenotype. Hepatic
      expression of most mRNAs is not altered in Cnot3(+/-) vis-a-vis wild-type mice.
      However, the levels of specific mRNAs, such as those coding for energy metabolism
      related PDK4 and IGFBP1, are increased in Cnot3(+/-) hepatocytes, having poly(A)
      tails that are longer than those seen in control cells. We provide evidence that
      CNOT3 is involved in recruitment of the CCR4-NOT deadenylase to the 3' end of
      specific mRNAs. Finally, as CNOT3 levels in the liver and white adipose tissues
      decrease upon fasting, we propose that CNOT3 responds to feeding conditions to
      regulate deadenylation-specific mRNAs and energy metabolism.

PMID- 21897368
TI  - A single copy of SecYEG is sufficient for preprotein translocation.
AB  - The heterotrimeric SecYEG complex comprises a protein-conducting channel in the
      bacterial cytoplasmic membrane. SecYEG functions together with the motor protein
      SecA in preprotein translocation. Here, we have addressed the functional
      oligomeric state of SecYEG when actively engaged in preprotein translocation. We
      reconstituted functional SecYEG complexes labelled with fluorescent markers into
      giant unilamellar vesicles at a natively low density. Forster's resonance energy
      transfer and fluorescence (cross-) correlation spectroscopy with single-molecule
      sensitivity allowed for independent observations of the SecYEG and preprotein
      dynamics, as well as complex formation. In the presence of ATP and SecA up to 80%
      of the SecYEG complexes were loaded with a preprotein translocation intermediate.
      Neither the interaction with SecA nor preprotein translocation resulted in the
      formation of SecYEG oligomers, whereas such oligomers can be detected when
      enforced by crosslinking. These data imply that the SecYEG monomer is sufficient
      to form a functional translocon in the lipid membrane.

PMID- 21897370
TI  - Responsive nematic gels from the self-assembly of aqueous nanofibres.
AB  - Aqueous nanofibres constructed by the self-assembly of small amphiphilic
      molecules can become entangled to form hydrogels that have a variety of
      applications including tissue engineering, and controlled drug delivery. The
      hydrogels are formed through the random physical cross-linkings of flexible
      nanofibres. Here we report that self-assembled nanofibres with a nematic
      substructure are aligned into a nematic liquid crystal and are spontaneously
      fixed in the aligned state to give rise to anisotropic gels. The liquid-crystal
      gels respond to temperature by transforming into a fluid solution upon cooling.
      Thus, the nanofibre solution can be mixed with cells at room temperature and then
      can be transformed into gels to encapsulate the cells in a three-dimensional
      environment upon being heated to physiological temperatures. We found that the
      cells grow within the three-dimensional networks without compromising the cell
      viability, and that subsequent cooling triggers the encapsulated cells to be
      released through a sol-gel transition.

PMID- 21897369
TI  - iASPP/p63 autoregulatory feedback loop is required for the homeostasis of
      stratified epithelia.
AB  - iASPP, an inhibitory member of the ASPP (apoptosis stimulating protein of p53)
      family, is an evolutionarily conserved inhibitor of p53 which is frequently
      upregulated in human cancers. However, little is known about the role of iASPP
      under physiological conditions. Here, we report that iASPP is a critical
      regulator of epithelial development. We demonstrate a novel autoregulatory
      feedback loop which controls crucial physiological activities by linking iASPP to
      p63, via two previously unreported microRNAs, miR-574-3p and miR-720. By
      investigating its function in stratified epithelia, we show that iASPP
      participates in the p63-mediated epithelial integrity program by regulating the
      expression of genes essential for cell adhesion. Silencing of iASPP in
      keratinocytes by RNA interference promotes and accelerates a differentiation
      pathway, which also affects and slowdown cellular proliferation. Taken together,
      these data reveal iASPP as a key regulator of epithelial homeostasis.

PMID- 21897372
TI  - Surfactant-enabled epitaxy through control of growth mode with chemical boundary
      conditions.
AB  - Property coupling at interfaces between active materials is a rich source of
      functionality, if defect densities are low, interfaces are smooth and the
      microstructure is featureless. Conventional synthesis techniques generally fail
      to achieve this when materials have highly dissimilar structure, symmetry and
      bond type-precisely when the potential for property engineering is most
      pronounced. Here we present a general synthesis methodology, involving systematic
      control of the chemical boundary conditions in situ, by which the crystal habit,
      and thus growth mode, can be actively engineered. In so doing, we establish the
      capability for layer-by-layer deposition in systems that otherwise default to
      island formation and grainy morphology. This technique is demonstrated via
      atomically smooth {111} calcium oxide films on (0001) gallium nitride. The
      operative surfactant-based mechanism is verified by temperature-dependent
      predictions from ab initio thermodynamic calculations. Calcium oxide films with
      smooth morphology exhibit a three order of magnitude enhancement of insulation
      resistance.

PMID- 21897371
TI  - Smad6-specific recruitment of Smurf E3 ligases mediates TGF-beta1-induced
      degradation of MyD88 in TLR4 signalling.
AB  - Transforming growth factor-beta (TGF-beta) is a potent anti-inflammatory cytokine
      that regulates interleukin-1 receptor and Toll-like receptor (TLR) signalling.
      Here we show a novel mechanism where TGF-beta1-induced K48-linked
      polyubiquitination and degradation of the adaptor MyD88 protein is dependent on
      the Smad6 protein, but not Smad7, and mediated by recruitment of the Smad
      ubiquitin regulator factor proteins, Smurf1 and Smurf2, which have E3-ubiquitin
      ligase activity. Smurf1 interaction with MyD88 appears to be mediated by Smad6,
      and Smurf2 interaction by Smurf1. Knockdown of endogenous Smurf1 or Smurf2 by RNA
      interference significantly suppresses the anti-inflammatory effects of TGF-beta1
      by preventing lipopolysaccharide-induced NF-kappaB nuclear translocation,
      resulting in de-suppression of pro-inflammatory gene expression. Similar effects
      are observed on the lipoteichoic-acid-induced TLR2 pathway, which is also MyD88
      dependent, but not the MyD88-independent TLR3 pathway. Thus, our results suggest
      that MyD88 degradation driven by the Smad6-Smurf pathway is a novel mechanism for
      TGF-beta1-mediated negative regulation of MyD88-dependent pro-inflammatory
      signalling.

PMID- 21897373
TI  - Bacterial Pili exploit integrin machinery to promote immune activation and
      efficient blood-brain barrier penetration.
AB  - Group B Streptococcus (GBS) is the leading cause of meningitis in newborn
      infants. Bacterial cell surface appendages, known as pili, have been recently
      described in streptococcal pathogens, including GBS. The pilus tip adhesin, PilA,
      contributes to GBS adherence to blood-brain barrier (BBB) endothelium; however,
      the host receptor and the contribution of PilA in central nervous system (CNS)
      disease pathogenesis are unknown. Here we show that PilA binds collagen, which
      promotes GBS interaction with the alpha2beta1 integrin resulting in activation of
      host chemokine expression and neutrophil recruitment during infection. Mice
      infected with the PilA-deficient mutant exhibit delayed mortality, a decrease in
      neutrophil infiltration and bacterial CNS dissemination. We find that PilA
      mediated virulence is dependent on neutrophil influx as neutrophil depletion
      results in a decrease in BBB permeability and GBS-BBB penetration. Our results
      suggest that the bacterial pilus, specifically the PilA adhesin, has a dual role
      in immune activation and bacterial entry into the CNS.

PMID- 21897383
TI  - Graphene: show of adhesive strength.

PMID- 21897378
TI  - Animal models for nickel allergy.

PMID- 21897384
TI  - Biomaterials: a natural source of nanowires.

PMID- 21897375
TI  - Microfluidic quadrupole and floating concentration gradient.
AB  - The concept of fluidic multipoles, in analogy to electrostatics, has long been
      known as a particular class of solutions of the Navier-Stokes equation in
      potential flows; however, experimental observations of fluidic multipoles and of
      their characteristics have not been reported yet. Here we present a two
      dimensional microfluidic quadrupole and a theoretical analysis consistent with
      the experimental observations. The microfluidic quadrupole was formed by
      simultaneously injecting and aspirating fluids from two pairs of opposing
      apertures in a narrow gap formed between a microfluidic probe and a substrate. A
      stagnation point was formed at the centre of the microfluidic quadrupole, and its
      position could be rapidly adjusted hydrodynamically. Following the injection of a
      solute through one of the poles, a stationary, tunable, and movable-that is,
      'floating'-concentration gradient was formed at the stagnation point. Our results
      lay the foundation for future combined experimental and theoretical exploration
      of microfluidic planar multipoles including convective-diffusive phenomena.

PMID- 21897376
TI  - In-vitro derived germinal centre B cells differentially generate memory B or
      plasma cells in vivo.
AB  - In response to T cell-dependent antigens, B cells proliferate extensively to form
      germinal centres (GC), and then differentiate into memory B (B(mem)) cells or
      long-lived plasma cells (LLPCs) by largely unknown mechanisms. Here we show a new
      culture system in which mouse naive B cells undergo massive expansion and isotype
      switching, and generate GC-phenotype B (iGB) cells. The iGB cells expressing IgG1
      or IgM/D, but not IgE, differentiate into B(mem) cells in vivo after adoptive
      transfer and can elicit rapid immune responses with the help of cognate T cells.
      Secondary culture with IL-21 maintains the proliferation of the iGB cells, while
      shifting their in vivo developmental fate from B(mem) cells to LLPCs, an outcome
      that can be reversed by withdrawal of IL-21 in tertiary cultures. Thus, this
      system enables in vitro manipulation of B-cell fate, into either B(mem) cells or
      LLPCs, and will facilitate dissection of GC-B cell differentiation programs.

PMID- 21897385
TI  - Nanoparticles: self-assembly finds its own limits.

PMID- 21897386
TI  - Assessment of treatment-induced female sexual morbidity in oncology: is this a
      part of routine medical follow-up after radical pelvic radiotherapy?
AB  - BACKGROUND: Oncology follow-up has traditionally prioritised disease surveillance
      and the assessment and management of symptoms associated with cancer and its
      treatment. Over the past decade, the focus on late effects of treatment has
      increased, particularly those that have an adverse effect on long-term function
      and quality of life. The aim of this research was to explore factors that
      influence the identification of treatment-induced female sexual difficulties in
      routine oncology follow-up after radical pelvic radiotherapy. METHODS: A
      structured observation schedule was used to systematically record topics
      discussed in 69 radiotherapy follow-up consultations observed over a 5-month
      period. RESULTS: Analysis suggests that physical toxicity assessment focused on
      bowel (81%) and bladder (70%) symptoms. Vaginal toxicity was discussed less
      frequently (42%) and sexual issues were explored in only 25% of consultations.
      Formal recording of radiation toxicity through assessment questionnaires was
      limited to patients participating in clinical trials. Surveillance activity and
      the management of active physical symptoms predominated and psychosocial issues
      were addressed in only 42% of consultations. INTERPRETATION: Female sexual
      morbidity after pelvic radiotherapy remains a neglected aspect of routine follow
      up and cancer survivorship. Developments in both individual practice and service
      provision are necessary if the identification and management of treatment-induced
      female sexual difficulties is to be improved.

PMID- 21897387
TI  - Rapid non-genomic signalling by 17beta-oestradiol through c-Src involves mTOR
      dependent expression of HIF-1alpha in breast cancer cells.
AB  - BACKGROUND: Hypoxia-inducible factor 1 (HIF1) has been implicated in regulating
      many of the genes responsible for angiogenesis, erythropoiesis, glucose
      metabolism and cancer pathogenesis. In this study, we demonstrate that exposure
      of human breast cancer lines to 17beta-oestradiol (E2) rapidly induced the
      expression of HIF-1alpha, the regulated subunit of HIF1, in normoxic condition.
      Hypoxia-inducible factor-1alpha is normally degraded in normoxia through
      ubiquitination-mediated proteolysis, whereas hypoxia modulates HIF-1alpha level
      by inhibiting ubiquitination-mediated degradation. METHODS: Oestradiol-induced
      accumulation of HIF-1alpha in breast cancer lines was detected by western blot
      analysis and its promoter activity was measured by HIF1 reporter assay. Molecular
      signalling of oestradiol-mediated HIF-1alpha expression was studied using
      specific pharmacological inhibitors and small interference RNA by co
      immunoprecipitation and western blotting analysis. RESULTS: Oestradiol has been
      observed to rapidly activate the nongenomic signalling cascade leading to HIF
      1alpha protein synthesis. The results define a signalling pathway in breast
      cancer cells whereby oestradiol induces a rapid protein-protein interaction of
      ERalpha-c-Src-PI3K, resulting in the activation of PI3K/AKT pathway leading to
      mammalian target of rapamycin (mTOR) phosphorylation. The mTOR then stimulates
      translation by phosphorylating p70 S6 kinase and 4EB-P1, modulating HIF-1alpha
      protein synthesis. Oestradiol-stimulated HIF-1alpha activity was inhibited by
      either siRNA or pharmacological inhibitors to ERalpha, c-Src, PI3K and mTOR,
      providing a mechanism for the modulation of HIF-1alpha protein synthesis.
      CONCLUSION: These results show oestradiol-induced expression of HIF-1alpha,
      downstream of the ERalpha/c-Src/PI3K/AKT/mTOR pathway in human breast cancer
      cells.

PMID- 21897388
TI  - GSTPi-positive tumour microenvironment-associated fibroblasts are significantly
      associated with GSTPi-negative cancer cells in paired cases of primary invasive
      breast cancer and axillary lymph node metastases.
AB  - BACKGROUND: Glutathione S-transferase Pi (GSTPi) expression is one of the
      factors, which is known to be associated with development of resistance to
      chemotherapeutics in cancer patients, including those with breast cancer. Yet,
      its expression has been reported to be undetectable in cancer cells in high
      percent of patients with primary breast cancer. However, GSTPi expression in
      stromal cells in breast tumour microenvironment, namely cancer-associated
      fibroblast (CAF), which is recognised to have major roles in cancer progression,
      remains poorly reported. METHODS: The aim of the study was to determine the
      expression of GSTPi; vimetin, a fibroblast-associated cytoskeleton protein; and
      alpha-smooth muscle actin (alpha-SMA), a known marker of CAF in breast cancer
      tissue, by immunohistochemical staining method in consecutive histologic sections
      of formalin-fixed and paraffin-embedded tissue biopsy specimens from a cohort of
      39 paired cases of patients with invasive breast cancer and the corresponding
      axillary lymph nodes metastases. RESULTS: Ductal and acinar luminal epithelial
      cells, myoepithelial cells and surrounding fibroblasts exhibited a homogeneous
      cytoplasmic reactivity with anti-GSTPi antibody in 11 of 11 cases of benign
      breast tissue biopsies. The vimentin-positive fibroblasts were unreactive with
      anti-alpha-SMA antibody. Loss of GSTPi expression was observed in breast cancer
      cells, at both the primary and metastatic sites, in 31 of 39 paired cases, as
      compared with benign breast epithelial cells (Fisher's exact test P<0.001). A
      significant association was observed between GSTPi-positive, vimentin-positive
      and alpha-SMA-positive fibroblast in tumour microenvironment at both sites.
      CONCLUSION: This is an original report of demonstration of a significance
      association between tumour microenvironment-associated GSTPi-positive CAF
      (vimentin/alpha-SMA-positive) and the GSTPi-negative cancer cells in paired cases
      of primary invasive breast cancer and the corresponding axillary lymph nodes
      metastases.

PMID- 21897390
TI  - Socioeconomic position, stage of lung cancer and time between referral and
      diagnosis in Denmark, 2001-2008.
AB  - INTRODUCTION: We investigated the association between socioeconomic position,
      stage at diagnosis, and length of period between referral and diagnosis in a
      nationwide cohort of lung cancer patients. METHODS: Through the Danish Lung
      Cancer Register, we identified 18,103 persons diagnosed with lung cancer (small
      cell and non-small cell) in Denmark, 2001-2008, and obtained information on
      socioeconomic position and comorbidity from nationwide administrative registries.
      The odds ratio (OR) for a diagnosis of advanced-stage lung cancer (stages IIIB
      IV) and for a diagnosis >28 days after referral were analysed by multivariate
      logistic regression models. RESULTS: The adjusted OR for advanced-stage lung
      cancer was reduced among persons with higher education (OR, 0.92; 95% confidence
      interval (CI), 0.84-0.99), was increased in persons living alone (OR, 1.06; 95%
      CI, 1.01-1.13) and decreased stepwise with increasing comorbidity. Higher
      education was associated with a reduced OR for >28 days between referral and
      diagnosis as was high income in early-stage patients. Male gender, age and severe
      comorbidity were associated with increased ORs in advanced-stage patients.
      INTERPRETATION: Differences by socioeconomic position in stage at diagnosis and
      in the period between referral and diagnosis indicate that vulnerable patients
      presenting with lung cancer symptoms require special attention.

PMID- 21897389
TI  - Meat-cooking mutagens and risk of renal cell carcinoma.
AB  - BACKGROUND: High-temperature cooked meat contains two families of carcinogens,
      heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Given the
      kidneys' role in metabolism and urinary excretion of these compounds, we
      investigated meat-derived mutagens, as well as meat intake and cooking methods,
      in a population-based case-control study conducted in metropolitan Detroit and
      Chicago. METHODS: Newly diagnosed, histologically confirmed adenocarcinoma of the
      renal parenchyma (renal cell carcinoma (RCC)) cases (n=1192) were frequency
      matched on age, sex, and race to controls (n=1175). The interviewer-administered
      Diet History Questionnaire (DHQ) included queries for meat-cooking methods and
      doneness with photographic aids. Levels of meat mutagens were estimated using the
      DHQ in conjunction with the CHARRED database. RESULTS: The risk of RCC increased
      with intake of barbecued meat (P(trend)=0.04) and the PAH, benzo(a)pyrene (BaP)
      (multivariable-adjusted odds ratio and 95% confidence interval, highest vs lowest
      quartile: 1.50 (1.14, 1.95), P(trend)=0.001). With increasing BaP intake, the
      risk of RCC was more than twofold in African Americans and current smokers
      (P(interaction)<0.05). We found no association for HCAs or overall meat intake.
      CONCLUSION: BaP intake, a PAH in barbecued meat, was positively associated with
      RCC. These biologically plausible findings advocate further epidemiological
      investigation into dietary intake of BaP and risk of RCC.

PMID- 21897391
TI  - Geographic remoteness and risk of advanced colorectal cancer at diagnosis in
      Queensland: a multilevel study.
AB  - BACKGROUND: We examine the relationships between geographic remoteness, area
      disadvantage and risk of advanced colorectal cancer. METHODS: Multilevel models
      were used to assess the area- and individual-level contributions to the risk of
      advanced disease among people aged 20-79 years diagnosed with colorectal cancer
      in Queensland, Australia between 1997 and 2007 (n=18,561). RESULTS: Multilevel
      analysis showed that colorectal cancer patients living in inner regional
      (OR=1.09, 1.01-1.19) and outer regional (OR=1.11, 1.01-1.22) areas were
      significantly more likely to be diagnosed with advanced cancer than those in
      major cities (P=0.045) after adjusting for individual-level variables. The best
      fitting final model did not include area disadvantage. Stratified analysis
      suggested this remoteness effect was limited to people diagnosed with colon
      cancer (P=0.048) and not significant for rectal cancer patients (P=0.873).
      CONCLUSION: Given the relationship between stage and survival outcomes, it is
      imperative that the reasons for these rurality inequities in advanced disease be
      identified and addressed.

PMID- 21897392
TI  - Activin A inhibits vascular endothelial cell growth and suppresses tumour
      angiogenesis in gastric cancer.
AB  - BACKGROUND: Activin A is a multi-functional cytokine belonging to the
      transforming growth factor-beta (TGF-beta) superfamily; however, the effect of
      activin A on angiogenesis remains largely unclear. We found that inhibin beta A
      subunit (INHBA) mRNA is overexpressed in gastric cancer (GC) specimens and
      investigated the effect of activin A, a homodimer of INHBA, on angiogenesis in
      GC. METHODS: Anti-angiogenic effects of activin A via p21 induction were
      evaluated using human umbilical vein endothelial cells (HUVECs) in vitro and a
      stable INHBA-introduced GC cell line in vivo. RESULTS: Compared with TGF-beta,
      activin A potently inhibited the cellular proliferation and tube formation of
      HUVECs with induction of p21. A promoter assay and a chromatin
      immunoprecipitation assay revealed that activin A directly regulates p21
      transcriptional activity through Smads. Stable p21-knockdown significantly
      enhanced the cellular proliferation of HUVECs. Notably, stable p21-knockdown
      exhibited a resistance to activin-mediated growth inhibition in HUVECs,
      indicating that p21 induction has a key role on activin A-mediated growth
      inhibition in vascular endothelial cells. Finally, a stable INHBA-introduced GC
      cell line exhibited a decrease in tumour growth and angiogenesis in vivo.
      CONCLUSION: Our findings highlight the suppressive role of activin A, unlike TGF
      beta, on tumour growth and angiogenesis in GC.

PMID- 21897393
TI  - Incidence trends of vestibular schwannomas in Denmark, Finland, Norway and Sweden
      in 1987-2007.
AB  - BACKGROUND: The reported incidence rates of vestibular schwannomas (VS) vary
      substantially, but it is unclear as to what extent the variation reflects
      differences in risk or recording practices. Our aim was to describe the incidence
      rates of VS in Denmark, Finland, Norway and Sweden between 1987 and 2007.
      METHODS: Comprehensive data were available from all registries only for the
      period from 1987 to 2007. An analysis of a longer time period (1965-2007) was
      conducted with the Norwegian and Swedish data. RESULTS: The average age
      standardised incidence rates during 1987-2007 varied from 6.1 per 1,000,000
      person-years (95% confidence interval (CI), 5.4-6.7) among Finnish men to 11.6
      (95% CI, 10.4-12.7) in Danish men, and from 6.4 per 1,000,000 person-years (95%
      CI, 5.7-7.0) among Swedish women to 11.6 (95% CI, 10.5-12.8) among Danish women.
      An overall annual increase of 3.0% (95% CI 2.1-3.9) was observed when all
      countries and both sexes were combined, with considerable differences between
      countries. However, the practices of both reporting and coding VS cases varied
      markedly between countries and over time, which poses a challenge for
      interpretation of the results. CONCLUSION: The overall incidence of VS increased
      in all the four Nordic countries combined between 1987 and 2007, with marked
      differences between countries. However, the incidence rates more or less
      stabilised in the late 1990s, showing relatively constant incidence rates and
      even some decline after 2000.

PMID- 21897394
TI  - The Breakthrough Generations Study: design of a long-term UK cohort study to
      investigate breast cancer aetiology.
AB  - BACKGROUND: The rationale, design, recruitment and follow-up methods are
      described for the Breakthrough Generations Study, a UK cohort study started in
      2003, targeted at investigation of breast cancer aetiology. METHODS: Cohort
      members have been recruited by a participant referral method intended to assemble
      economically a large general population cohort from whom detailed questionnaire
      information and blood samples can be obtained repeatedly over decades, with high
      completeness of follow-up and inclusion of large numbers of related individuals.
      'First-generation' recruits were women contacted directly, or who volunteered
      directly, to join the study. They nominated female friends and family, whom we
      contacted, and those who joined ('second generation') nominated others,
      reiterated for up to 28 generations. RESULTS: The method has successfully been
      used during 2003-2011 to recruit 112,049 motivated participants with a broad
      geographic and socioeconomic distribution, aged 16-102 years, who have completed
      detailed questionnaires; 92% of the participants gave blood samples at
      recruitment. When eligible, 21/2 years after recruitment, >98% completed the
      first follow-up questionnaire. Thirty percent are first-degree relatives of other
      study members. CONCLUSION: The 'generational' recruitment method has enabled
      recruitment of a large cohort who appear to have the commitment to enable long
      term continuing data and sample collection, to investigate the effects of
      changing endogenous and exogenous factors on cancer risk.

PMID- 21897395
TI  - HPV testing as a triage for borderline or mild dyskaryosis on cervical cytology:
      results from the Sentinel Sites study.
AB  - BACKGROUND: Earlier pilot studies of human papillomavirus (HPV) triage concluded
      that HPV triage was feasible and cost-effective. The aim of the present study was
      to study the impact of wider rollout of HPV triage for women with low-grade
      cytology on colposcopy referral and outcomes. METHODS: Human papillomavirus
      testing of liquid-based cytology (LBC) samples showing low-grade abnormalities
      was used to select women for colposcopy referral at six sites in England. Samples
      from 10,051 women aged 25-64 years with routine call or recall cytology reported
      as borderline or mild dyskaryosis were included. RESULTS: Human papillomavirus
      positive rates were 53.7% in women with borderline cytology and 83.9% in those
      with mild dyskaryosis. The range between sites was 34.8-73.3% for borderline
      cytology, and 73.4-91.6% for mild dyskaryosis. In the single site using both LBC
      technologies there was no difference in rates between the two technologies. The
      positive predictive value of an HPV test was 16.3% for CIN2 or worse and 6.1% for
      CIN3 or worse, although there was considerable variation between sites.
      CONCLUSION: Triaging women with borderline cytological abnormalities and mild
      dyskaryosis with HPV testing would allow approximately a third of these women to
      be returned immediately to routine recall, and for a substantial proportion to be
      referred for colposcopy without repeat cytology. Variation in HPV-positive rates
      results in differing colposcopy workload.

PMID- 21897398
TI  - Red blood cell-incompatible allogeneic hematopoietic progenitor cell
      transplantation.
AB  - Transplantation of hematopoietic progenitor cells from red cell-incompatible
      donors occurs in 30-50% of patients. Immediate and delayed hemolytic transfusion
      reactions are expected complications of red cell-disparate transplantation and
      both ABO and other red cell systems such as Kidd and rhesus can be involved. The
      immunohematological consequences of red cell-incompatible transplantation include
      delayed red blood cell recovery, pure red cell aplasia and delayed hemolysis from
      viable lymphocytes carried in the graft ('passenger lymphocytes'). The risks of
      these reactions, which may be abrupt in onset and fatal, are ameliorated by graft
      processing and proper blood component support. Red blood cell antigens are
      expressed on endothelial and epithelial tissues in the body and could serve to
      increase the risk of GvHD. Mouse models indicate that blood cell antigens may
      function as minor histocompatibility antigens affecting engraftment. Similar
      observations have been found in early studies of human transplantation for
      transfused recipients, although current conditioning and immunosuppressive
      regimens appear to overcome this affect. No deleterious effects from the use of
      red cell-incompatible hematopoietic grafts on transplant outcomes, such as
      granulocyte and platelet engraftments, the incidences of acute or chronic GvHD,
      relapse risk or OS, have been consistently demonstrated. Most studies, however,
      include limited number of patients, varying diagnoses and differing treatment
      regimens, complicating the detection of an effect of ABO-incompatible
      transplantation. Classification of patients by ABO phenotype ignoring the allelic
      differences of these antigens also may obscure the effect of red cell
      incompatible transplantation on transplant outcomes.

PMID- 21897396
TI  - Prognostic role of CIP2A expression in serous ovarian cancer.
AB  - BACKGROUND: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an
      oncoprotein expressed in several solid cancers. Our purpose was to study its role
      in serous ovarian cancer patients, and the association to clinicopathological
      variables and molecular markers. METHODS: We collected retrospectively 562
      consecutive serous ovarian cancer patients treated at the Helsinki University
      Central Hospital. We stained tumour tissue microarrays for CIP2A by
      immunohistochemistry and constructed survival curves according to the Kaplan
      Meier method. Associations to clinicopathological and molecular markers were
      assessed by the chi(2)-test. RESULTS: We found strong cytoplasmic CIP2A
      immunoreactivity in 212 (40.4%) specimens, weak positivity in 222 (42.4%)
      specimens, and negative in 90 (17.2%). Immunopositive CIP2A expression was
      associated with high grade (P<0.0001), advanced stage (P=0.0005), and aneuploidy
      (P=0.001, chi(2)-test). Cancerous inhibitor of protein phosphatase 2A
      overexpression was also associated with EGFR protein expression (P=0.006) and
      EGFR amplification (P=0.043). Strong cytoplasmic CIP2A immunopositivity predicted
      poor outcome in ovarian cancer patients (P<0.0001, log-rank test). CONCLUSION:
      Our results show that CIP2A associates with reduced survival and parameters
      associated with high grade in ovarian cancer patients, and may thus be one of the
      factors that identify aggressive subtype (type II) of this disease.

PMID- 21897400
TI  - Lobophorins E and F, new spirotetronate antibiotics from a South China Sea
      derived Streptomyces sp. SCSIO 01127.
AB  - The strain SCSIO 01127, isolated from the South China Sea sediment, was
      identified as a member of Streptomyces by the 16S rDNA sequence analysis. Two new
      spirotetronate antibiotics lobophorins E (1) and F (2), along with two known
      analogs lobophorins A (3) and B (4), were isolated from Streptomyces sp. SCSIO
      01127. Their structures were elucidated on the basis of detailed IR, NMR and MS
      spectroscopic analyses. The new compound lobophorin F (2) showed antibacterial
      activities against Staphylococcus aureus ATCC 29213 and Enterococcus faecalis
      ATCC 29212 with MIC values of 8 MUg ml(-1) for both the strains, better than that
      of lobophorin B (4). Lobophorin F (2) also displayed better cytotoxic activities
      than lobophorin B (4), with IC(50) of 6.82, 2.93 and 3.16 MUM against SF-268, MCF
      7 and NCI-H460, respectively.

PMID- 21897401
TI  - Calcium and vitamin D for chronic disease: a time for action.

PMID- 21897403
TI  - PQRI, VBP, ACO, eRx, MoC ...: understanding the lexicon of health-care-reform
      legislation.

PMID- 21897404
TI  - Informed consent in the older adult: OSCEs for assessing fellows' ACGME and
      geriatric gastroenterology competencies.
AB  - OBJECTIVES: The American Gastroenterological Association fellowship curriculum
      identifies geriatric components for gastroenterology (GI) training; however, few
      tools are available for this purpose. Using an objective structured clinical
      examination (OSCE), we aimed to assess ACGME competencies of communication,
      professionalism, and geriatric-specific patient care among GI fellows. METHODS:
      We developed an informed-consent case involving a geriatric patient who needs
      surveillance colonoscopy. We used a validated faculty skills checklist to rate
      fellows across three competency domains. Fifteen fellows from four GI training
      programs participated. RESULTS: Although the fellows excelled at communication
      and professionalism, only 51% excelled at geriatric-specific patient-care skills.
      Fellows were least likely to demonstrate collaboration with the patient, to
      assess patient understanding, and to explain the limits of the test.
      Communication and geriatric-specific skills were correlated. CONCLUSIONS: OSCEs
      are a feasible method for assessing geriatric-related ACGME competencies for
      fellows. The results highlight the need for curriculum development.

PMID- 21897405
TI  - Images of the month. Endoscopic views of (left) a fistula orifice in the insicura
      angularis and (right) a perforated duodenal bulb ulcer.

PMID- 21897411
TI  - Losses to follow-up limit conclusions regarding the efficacy of branched-chain
      amino acids in patients with hepatic encephalopathy.

PMID- 21897412
TI  - Is the lymphoma risk reduced in viral hepatitis? A cirrhotic patient with triple
      malignancies.

PMID- 21897414
TI  - Role of 5-aminosalicylate in preventing colorectal cancer.

PMID- 21897417
TI  - Dysplastic Barrett's esophagus in cirrhosis: a treatment dilemma.

PMID- 21897416
TI  - Low-cost endomicroscopy in the esophagus and colon.

PMID- 21897418
TI  - Lactulose: how many ways can one drug be prescribed?

PMID- 21897419
TI  - HIV testing: a must for patients with inflammatory bowel disease?

PMID- 21897422
TI  - Variations in truncal body circumferences affect fat mass quantification with
      bioimpedance analysis.
AB  - OBJECTIVE: To test the hypothesis that variations in trunk circumferences
      influence the accuracy of bioimpedance analysis (BIA) for assessment of percent
      fat mass (%FM). SUBJECTS AND METHODS: %FM was predicted with BIA, and compared
      with air-displacement plethysmography (ADP) in a small sample of 35 overweight
      (OW), 21 normal weight and 8 underweight volunteers. Waist and hip circumferences
      were assessed, and 15 of the OW subjects were measured before and after weight
      reduction. RESULTS: BIA and ADP provided similar cross-sectional estimates of
      group mean %FM (28.9+/-10.0 and 31.3+/-13.0%, respectively). However, within
      individuals, there were large between-method differences (Diff(BIA-ADP)) ranging
      from -13 to +13 %FM. Furthermore, we found a systematic bias of BIA related to
      the degree of adiposity. Consequently, %FM and fat mass loss during weight
      reduction in OW were underestimated with BIA when compared with ADP. Waist and
      hip circumferences were inversely associated with resistance (R) and reactance
      (P<0.01), and with Diff(BIA-ADP) (P<0.001). In women, the variability in hip
      circumference explained 76%, and in men, the variability in waist circumference
      explained 59% of Diff(BIA-ADP). CONCLUSION: Resistance changes associated with
      variations in trunk circumferences decrease resistance, and therefore impair the
      accuracy of BIA to assess %FM.

PMID- 21897423
TI  - Vitamin D and parathormone levels of late-preterm formula fed infants during the
      first year of life.
AB  - BACKGROUND/OBJECTIVES: Preterm infants are at risk for low vitamin D but
      documentation on late-preterm infants is sparse. This prospective study monitored
      longitudinally vitamin D and parathormone (PTH) levels in late-preterm formula
      fed infants during the first year of life, taking into consideration in utero and
      postnatal growth, and season and diet. SUBJECTS/METHODS: The study population
      comprised 128 infants of gestational age (GA) 32-36 weeks, of which 102 were
      appropriate (AGA) and the remaining 26 were small for GA (SGA). Serum levels of
      vitamin D (25(OH)D), PTH calcium, phosphate (P) and alkaline phosphate were
      estimated at 2 and 6 weeks, and at 3, 6, 9 and 12 months of age. RESULTS: The
      25(OH)D levels were relatively low at 2 and 6 weeks in both AGA and SGA infants
      (21+/-11, 20+/-7 ng/ml and 25+/-16, 23+/-8 ng/ml, respectively), but increased at
      6 months (45+/-14, 47+/-10 ng/ml) and remained stable thereafter. SGA infants had
      lower 25(OH)D levels at 9 and 12 months (AGA 45+/-14, 47+/-18 ng/ml vs SGA 38+/
      13, 37+/-13 ng/ml, P<0.05). Deficiency of 25(OH)D (<20 ng/ml) was found in 18.5%
      of measurements in 92 (72%) infants, and its insufficiency (20-32 ng/ml) was
      found in 29.2% of measurements in 99 (77.3%) infants. Most measurements with
      vitamin D <32 ng/ml were observed at the first three study points, where PTH
      showed an inverse association with 25(OH)D, reaching a plateau thereafter.
      CONCLUSIONS: Late-preterm, formula fed infants may have suboptimal vitamin D
      levels and elevated PTH, especially, during the first 3 months. Those born SGA
      may have lower vitamin D levels up to the end of the first year of life.

PMID- 21897425
TI  - Hypertension is statistically associated with higher body mass index but not with
      vitamin D level in a Thai population.
AB  - Vitamin D deficiency has been linked to hypertension. Although vitamin D
      deficiency is common in tropical regions, no data on its association with
      hypertension were available. We randomly selected 137 cases and controls whose
      plasma in 1985 was available for the assessment of vitamin D status and
      calculated the odds ratio of having hypertension in 1997. In all, 36% of the
      participants were vitamin D deficient. The odds ratio of having hypertension was
      marginally significant for vitamin D deficiency (0.59, P=0.05) and statistically
      significant for body mass index (BMI)-defined overweight (1.8, P=0.02). The
      inverse relationship between vitamin D deficiency and hypertension became
      statistically significant after further adjustment for BMI, high-density
      lipoprotein cholesterol and triglyceride (0.55, P=0.03). Stepwise regression
      identified BMI-defined overweight and vitamin D deficiency as the variables of
      significance in relation to hypertension. Our data suggest that vitamin D
      deficiency, although not a rarity in Thailand, was not associated with an
      increased risk of developing hypertension in Thai people.

PMID- 21897424
TI  - Significant inverse association of marine n-3 fatty acids with plasma fibrinogen
      levels in Japanese in Japan but not in whites or Japanese Americans.
AB  - BACKGROUND/OBJECTIVES: Numerous studies reported beneficial effects of marine n-3
      fatty acids (n-3 FAs) on cardiovascular disease (CVD) and its risk factors.
      However, the association of marine n-3 FAs with plasma fibrinogen, a risk factor
      for CVD, remains uncertain. SUBJECTS/METHODS: In a population-based, cross
      sectional study of 795 men aged 40-49 without CVD (262 whites in Allegheny
      County, Pennsylvania, USA, 302 Japanese in Kusatsu, Japan and 229 Japanese
      Americans in Honolulu, Hawaii, USA), we examined the association of marine n-3
      FAs with plasma fibrinogen. Serum FAs were measured by capillary gas-liquid
      chromatography. Marine n-3 FAs were defined as the sum of docosahexaenoic,
      eicosapentaenoic and docosapentaenoic acids. Plasma fibrinogen was measured by an
      automated clot-rate assay. Multiple linear regression analyses were performed to
      assess the association. RESULTS: White, Japanese and Japanese-American men had
      mean marine n-3 FAs levels of 3.47%, 8.78% and 4.46%, respectively. Japanese men
      had a significant inverse association of marine n-3 FAs with fibrinogen
      (standardized regression coefficient of -0.11, P=0.049), after adjusting for age,
      body-mass index and current smoking. The significant inverse association remained
      after further adjusting for diabetes, C-reactive protein, triglycerides and other
      variables. White or Japanese-American men did not show a significant association.
      CONCLUSIONS: We observed the significant inverse association of marine n-3 FAs
      with fibrinogen in Japanese, but not in whites or Japanese Americans. The
      observation suggests that marine n-3 FAs at very high levels, as seen in the
      Japanese, may decrease plasma fibrinogen levels.

PMID- 21897426
TI  - Clinical guidelines and enteral nutrition support: a survey of dietetic practice
      in the United Kingdom.
AB  - BACKGROUND: Artificial nutrition support is used in treating hospital patients
      and has been shown to reduce hospital stays. The NICE (National Collaborating
      Centre for Acute Care) guidelines are the first national consensus guidelines for
      dietetic practice in artificial nutrition. The aim of the current survey was to
      explore the influence of local and national guidelines, and clinical experience
      on enteral tube feeding practices in a large cohort of UK dietitians. METHODS: A
      cross-sectional anonymous online survey of UK registered dietitians was
      performed. RESULTS: A total of 681 responses were received. In all, 85% deemed
      'clinical experience' to be of greatest influence when initiating a tube feeding
      regimen; the influence of 'clinical experience' was significantly associated with
      the number of years in practice (P=<0.001). A total of 70% of respondents were
      aware of a department feeding protocol with 67% of protocols using a start rate
      of 24-49 ml/h; furthermore, 65% of respondents reported most commonly using a
      feeding start rate of 24-49 ml/h and 75% of them reported that their department
      had a protocol for preventing refeeding syndrome; 23% had mandatory
      implementation of NICE guidelines. CONCLUSIONS: Enteral feeding practice varies
      among practitioners. Clinical experience and published clinical guidelines have a
      pivotal role when treating adult patients that require enteral tube feeding.

PMID- 21897428
TI  - Cell death: Phagocytes whet their appetite.

PMID- 21897427
TI  - Next-generation transcriptome assembly.
AB  - Transcriptomics studies often rely on partial reference transcriptomes that fail
      to capture the full catalogue of transcripts and their variations. Recent
      advances in sequencing technologies and assembly algorithms have facilitated the
      reconstruction of the entire transcriptome by deep RNA sequencing (RNA-seq), even
      without a reference genome. However, transcriptome assembly from billions of RNA
      seq reads, which are often very short, poses a significant informatics challenge.
      This Review summarizes the recent developments in transcriptome assembly
      approaches - reference-based, de novo and combined strategies - along with some
      perspectives on transcriptome assembly in the near future.

PMID- 21897429
TI  - Chromatin: Stress inhibits replication through JNK1 signalling.

PMID- 21897431
TI  - Epigenetics: from father to son.

PMID- 21897432
TI  - Moment-to-moment signal variability in the human brain can inform models of
      stochastic facilitation now.

PMID- 21897434
TI  - A pathophysiological framework of hippocampal dysfunction in ageing and disease.
AB  - The hippocampal formation has been implicated in a growing number of disorders,
      from Alzheimer's disease and cognitive ageing to schizophrenia and depression.
      How can the hippocampal formation, a complex circuit that spans the temporal
      lobes, be involved in a range of such phenotypically diverse and mechanistically
      distinct disorders? Recent neuroimaging findings indicate that these disorders
      differentially target distinct subregions of the hippocampal circuit. In
      addition, some disorders are associated with hippocampal hypometabolism, whereas
      others show evidence of hypermetabolism. Interpreted in the context of the
      functional and molecular organization of the hippocampal circuit, these
      observations give rise to a unified pathophysiological framework of hippocampal
      dysfunction.

PMID- 21897437
TI  - Quantitative genetics of feeding behavior in two ecological races of the pea
      aphid, Acyrthosiphon pisum.
AB  - Much of the diversity of herbivorous insects stems from the adaptive divergence
      of populations onto different host plants. This often involves the evolution of
      specialized patterns of host acceptance that in turn lead to assortative mating
      for insects that mate exclusively on their hosts. Here, we explore the genetic
      architecture of feeding behavior in a herbivorous insect that has become a model
      for the study of incipient speciation, the pea aphid (Acyrthosiphon pisum). We
      use crosses between individuals specialized to either alfalfa or red clover in
      order to perform both a biometrical analysis and a quantitative trait locus (QTL)
      analysis of key feeding behaviors. For each character in each environment, Castle
      Wright's estimator for the number of effective factors segregating ranged from
      0.11 to 2.54. Similarly, between 0 and 3 QTLs were detected. In one case, a
      single QTL explained over 50% of the variance in the F2, suggesting that at least
      one gene (or a complex of tightly linked genes) has a major effect on feeding
      behavior in the pea aphid. However, the identified QTL explain only 23-73% of the
      genetic variance for these characters thus additional genes of minor effect are
      also involved. We found a variety of modes of gene action, including several
      cases of non-additive gene action. Our results suggest that feeding behavior in
      pea aphids is neither simple nor highly polygenic. The oligogenetic basis of
      variation in feeding behavior may facilitate host shifts, providing one
      explanation for the frequent divergence and speciation of herbivorous insects.

PMID- 21897436
TI  - Genetics and evolution of triatomines: from phylogeny to vector control.
AB  - Triatomines are hemipteran bugs acting as vectors of the protozoan parasite
      Trypanosoma cruzi. This parasite causes Chagas disease, one of the major
      parasitic diseases in the Americas. Studies of triatomine genetics and evolution
      have been particularly useful in the design of rational vector control
      strategies, and are reviewed here. The phylogeography of several triatomine
      species is now slowly emerging, and the struggle to reconcile the phenotypic,
      phylogenetic, ecological and epidemiological species concepts makes for a very
      dynamic field. Population genetic studies using different markers indicate a wide
      range of population structures, depending on the triatomine species, ranging from
      highly fragmented to mobile, interbreeding populations. Triatomines transmit T.
      cruzi in the context of complex interactions between the insect vectors, their
      bacterial symbionts and the parasites; however, an integrated view of the
      significance of these interactions in triatomine biology, evolution and in
      disease transmission is still lacking. The development of novel genetic markers,
      together with the ongoing sequencing of the Rhodnius prolixus genome and more
      integrative studies, will provide key tools to expanding our understanding of
      these important insect vectors and allow the design of improved vector control
      strategies.

PMID- 21897438
TI  - Evidence of a neo-sex chromosome in birds.
AB  - Neo-sex chromosomes often originate from sex chromosome-autosome fusions and
      constitute an important basis for the study of gene degeneration and expression
      in a sex chromosomal context. Neo-sex chromosomes are known from many animal and
      plant lineages, but have not been reported in birds, a group in which genome
      organization seems particularly stable. Following indications of sex linkage and
      unexpected sex-biased gene expression in warblers (Sylvioidea; Passeriformes), we
      have conducted an extensive marker analysis targeting 31 orthologues of loci on
      zebra finch chromosome 4a in five species, representative of independent branches
      of Passerida. We identified a region of sex linkage covering approximately the
      first half (10 Mb) of chromosome 4a, and associated to both Z and W chromosomes,
      in three Sylvioidea passerine species. Linkage analysis in an extended pedigree
      of one species additionally confirmed the association between this part of
      chromosome 4a and the Z chromosome. Markers located between 10 and 21 Mb of
      chromosome 4a showed no signs of sex linkage, suggesting that only half of the
      chromosome was involved in this transition. No sex linkage was observed in non
      Sylvioidea passerines, indicating that the neo-sex chromosome arose at the base
      of the Sylvioidea branch of the avian phylogeny, at 47.4-37.6 millions years ago
      (MYA), substantially later than the ancestral sex chromosomes (150 MYA). We
      hypothesize that the gene content of chromosome 4a might be relevant in its
      transition to a sex chromosome, based on the presence of genes (for example, the
      androgen receptor) that could offer a selective advantage when associated to Z
      linked sex determination loci.

PMID- 21897440
TI  - Effects of male fecundity, interindividual distance and anisotropic pollen
      dispersal on mating success in a Scots pine (Pinus sylvestris) seed orchard.
AB  - Quantifying the effect of pollen dispersal and flowering traits on mating success
      is essential for understanding evolutionary responses to changing environments
      and establishing strategies for forest tree breeding. This study examined,
      quantitatively, the effects of male fecundity, interindividual distance and
      anisotropic pollen dispersal on the mating success of Scots pine (Pinus
      sylvestris), utilizing a well-mapped Scots pine seed orchard. Paternity analysis
      of 1021 seeds sampled from 87 trees representing 28 clones showed that 53% of the
      seeds had at least one potential pollen parent within the orchard. Pronounced
      variation in paternal contribution was observed among clones. Variations in
      pollen production explained up to 78% of the variation in mating success, which
      was 11.2 times greater for clones producing the largest amount of pollen than for
      clones producing the least pollen. Mating success also varied with intertree
      distance and direction, which explained up to 28% of the variance. Fertilization
      between neighboring trees 2.3 m apart was 2.4 times more frequent than between
      trees 4.6 m apart, and up to 12.4 times higher for trees downwind of the presumed
      prevailing wind direction than for upwind trees. The effective number of pollen
      donors recorded in the seed orchard (12.2) was smaller than the theoretical
      expectation (19.7). Based on the empirical observations, a mating model that best
      describes the gene dispersal pattern in clonal seed orchards was constructed.

PMID- 21897441
TI  - Co-localisation of host plant resistance QTLs affecting the performance and
      feeding behaviour of the aphid Myzus persicae in the peach tree.
AB  - The architecture and action of quantitative trait loci (QTL) contributing to
      plant resistance mechanisms against aphids, the largest group of phloem-feeding
      insects, are not well understood. Comparative mapping of several components of
      resistance to the green peach aphid (Myzus persicae) was undertaken in Prunus
      davidiana, a wild species related to peach. An interspecific F(1) population of
      Prunus persica var. Summergrand * P. davidiana clone P1908 was scored for
      resistance (aphid colony development and foliar damage) and 17 aphid feeding
      behaviour traits monitored by means of the electrical penetration graph
      technique. Seven resistance QTLs were detected, individually explaining 6.1-43.1%
      of the phenotypic variation. Consistency was shown over several trials. Nine QTLs
      affecting aphid feeding behaviour were identified. All resistance QTLs except one
      co-located with QTLs underlying aphid feeding behaviour. A P. davidiana
      resistance allele at the major QTL was associated with drastic reductions in
      phloem sap ingestion by aphids, suggesting a phloem-based resistance mechanism.
      Resistance was also positively correlated with aphid salivation into sieve
      elements, suggesting an insect response to restore the appropriate conditions for
      ingestion after phloem occlusion. No significant QTL was found for traits
      characterising aphid mouthpart activity in plant tissues other than phloem
      vessels. Two QTLs with effects on aphid feeding behaviour but without effect on
      resistance were identified. SSR markers linked to the main QTLs involved in
      resistance are of potential use in marker-assisted selection for aphid
      resistance. Linking our results with the recent sequencing of the peach genome
      may help clarify the physiological resistance mechanisms.

PMID- 21897439
TI  - Next-generation hybridization and introgression.
AB  - Hybridization has a major role in evolution-from the introgression of important
      phenotypic traits between species, to the creation of new species through hybrid
      speciation. Molecular studies of hybridization aim to understand the class of
      hybrids and the frequency of introgression, detect the signature of ancient
      hybridization, and understand the behaviour of introgressed loci in their new
      genomic background. This often involves a large investment in the design and
      application of molecular markers, leading to a compromise between the depth and
      breadth of genomic data. New techniques designed to assay a large sub-section of
      the genome, in association with next-generation sequencing (NGS) technologies,
      will allow genome-wide hybridization and introgression studies in organisms with
      no prior sequence data. These detailed genotypic data will unite the breadth of
      sampling of loci characteristic of population genetics with the depth of sequence
      information associated with molecular phylogenetics. In this review, we assess
      the theoretical and methodological constraints that limit our understanding of
      natural hybridization, and promote the use of NGS for detecting hybridization and
      introgression between non-model organisms. We also make recommendations for the
      ways in which emerging techniques, such as pooled barcoded amplicon sequencing
      and restriction site-associated DNA tags, should be used to overcome current
      limitations, and enhance our understanding of this evolutionary significant
      process.

PMID- 21897435
TI  - The heterogeneous levels of linkage disequilibrium in white spruce genes and
      comparative analysis with other conifers.
AB  - In plants, knowledge about linkage disequilibrium (LD) is relevant for the design
      of efficient single-nucleotide polymorphism arrays in relation to their use in
      population and association genomics studies. Previous studies of conifer genes
      have shown LD to decay rapidly within gene limits, but exceptions have been
      reported. To evaluate the extent of heterogeneity of LD among conifer genes and
      its potential causes, we examined LD in 105 genes of white spruce (Picea glauca)
      by sequencing a panel of 48 haploid megagametophytes from natural populations and
      further compared it with LD in other conifer species. The average pairwise r(2)
      value was 0.19 (s.d.=0.19), and LD dropped quickly with a half-decay being
      reached at a distance of 65 nucleotides between sites. However, LD was
      significantly heterogeneous among genes. A first group of 29 genes had stronger
      LD (mean r(2)=0.28), and a second group of 38 genes had weaker LD (mean
      r(2)=0.12). While a strong relationship was found with the recombination rate,
      there was no obvious relationship between LD and functional classification. The
      level of nucleotide diversity, which was highly heterogeneous across genes, was
      also not significantly correlated with LD. A search for selection signatures
      highlighted significant deviations from the standard neutral model, which could
      be mostly attributed to recent demographic changes. Little evidence was seen for
      hitchhiking and clear relationships with LD. When compared among conifer species,
      on average, levels of LD were similar in genes from white spruce, Norway spruce
      and Scots pine, whereas loblolly pine and Douglas fir genes exhibited a
      significantly higher LD.

PMID- 21897442
TI  - Comparison of pollen gene flow among four European beech (Fagus sylvatica L.)
      populations characterized by different management regimes.
AB  - The study of the dispersal capability of a species can provide essential
      information for the management and conservation of its genetic variability.
      Comparison of gene flow rates among populations characterized by different
      management and evolutionary histories allows one to decipher the role of factors
      such as isolation and tree density on gene movements. We used two paternity
      analysis approaches and different strategies to handle the possible presence of
      genotyping errors to obtain robust estimates of pollen flow in four European
      beech (Fagus sylvatica L.) populations from Austria and France. In each country
      one of the two plots is located in an unmanaged forest; the other plots are
      managed with a shelterwood system and inside a colonization area (in Austria and
      France, respectively). The two paternity analysis approaches provided almost
      identical estimates of gene flow. In general, we found high pollen immigration
      (~75% of pollen from outside), with the exception of the plot from a highly
      isolated forest remnant (~50%). In the two unmanaged plots, the average within
      population pollen dispersal distances (from 80 to 184 m) were higher than
      previously estimated for beech. From the comparison between the Austrian managed
      and unmanaged plots, that are only 500 m apart, we found no evidence that either
      gene flow or reproductive success distributions were significantly altered by
      forest management. The investigated phenotypic traits (crown area, height,
      diameter and flowering phenology) were not significantly related with male
      reproductive success. Shelterwood seems to have an effect on the distribution of
      within-population pollen dispersal distances. In the managed plot, pollen
      dispersal distances were shorter, possibly because adult tree density is three
      fold (163 versus 57 trees per hectare) with respect to the unmanaged one.

PMID- 21897443
TI  - Advances in Alport syndrome diagnosis using next-generation sequencing.
AB  - Alport syndrome (ATS) is a hereditary nephropathy often associated with
      sensorineural hypoacusis and ocular abnormalities. Mutations in the COL4A5 gene
      cause X-linked ATS. Mutations in COL4A4 and COL4A3 genes have been reported in
      both autosomal recessive and autosomal dominant ATS. The conventional mutation
      screening, performed by DHPLC and/or Sanger sequencing, is time-consuming and has
      relatively high costs because of the absence of hot spots and to the high number
      of exons per gene: 51 (COL4A5), 48 (COL4A4) and 52 (COL4A3). Several months are
      usually necessary to complete the diagnosis, especially in cases with less
      informative pedigrees. To overcome these limitations, we designed a next
      generation sequencing (NGS) protocol enabling simultaneous detection of all
      possible variants in the three genes. We used a method coupling selective
      amplification to the 454 Roche DNA sequencing platform (Genome Sequencer junior).
      The application of this technology allowed us to identify the second mutation in
      two ATS patients (p.Ser1147Phe in COL4A3 and p.Arg1682Trp in COL4A4) and to
      reconsider the diagnosis of ATS in a third patient. This study, therefore,
      illustrates the successful application of NGS to mutation screening of Mendelian
      disorders with locus heterogeneity.

PMID- 21897444
TI  - Imaging genetics of FOXP2 in dyslexia.
AB  - Dyslexia is a developmental disorder characterised by extensive difficulties in
      the acquisition of reading or spelling. Genetic influence is estimated at 50-70%.
      However, the link between genetic variants and phenotypic deficits is largely
      unknown. Our aim was to investigate a role of genetic variants of FOXP2, a
      prominent speech and language gene, in dyslexia using imaging genetics. This
      technique combines functional magnetic resonance imaging (fMRI) and genetics to
      investigate relevance of genetic variants on brain activation. To our knowledge,
      this represents the first usage of fMRI-based imaging genetics in dyslexia. In an
      initial case/control study (n = 245) for prioritisation of FOXP2 polymorphisms
      for later use in imaging genetics, nine SNPs were selected. A non-synonymously
      coding mutation involved in verbal dyspraxia was also investigated. SNP
      rs12533005 showed nominally significant association with dyslexia (genotype GG
      odds ratio recessive model = 2.1 (95% confidence interval 1.1-3.9), P = 0.016). A
      correlated SNP was associated with altered expression of FOXP2 in vivo in human
      hippocampal tissue. Therefore, influence of the rs12533005-G risk variant on
      brain activity was studied. fMRI revealed a significant main effect for the
      factor 'genetic risk' in a temporo-parietal area involved in phonological
      processing as well as a significant interaction effect between the factors
      'disorder' and 'genetic risk' in activation of inferior frontal brain areas.
      Hence, our data may hint at a role of FOXP2 genetic variants in dyslexia-specific
      brain activation and demonstrate use of imaging genetics in dyslexia research.

PMID- 21897445
TI  - Detection of classical 17p11.2 deletions, an atypical deletion and RAI1
      alterations in patients with features suggestive of Smith-Magenis syndrome.
AB  - Smith-Magenis syndrome (SMS) is a complex disorder whose clinical features
      include mild to severe intellectual disability with speech delay, growth failure,
      brachycephaly, flat midface, short broad hands, and behavioral problems. SMS is
      typically caused by a large deletion on 17p11.2 that encompasses multiple genes
      including the retinoic acid induced 1, RAI1, gene or a mutation in the RAI1 gene.
      Here we have evaluated 30 patients with suspected SMS and identified SMS
      associated classical 17p11.2 deletions in six patients, an atypical deletion of
      ~139 kb that partially deletes the RAI1 gene in one patient, and RAI1 gene
      nonsynonymous alterations of unknown significance in two unrelated patients. The
      RAI1 mutant proteins showed no significant alterations in molecular weight,
      subcellular localization and transcriptional activity. Clinical features of
      patients with or without 17p11.2 deletions and mutations involving the RAI1 gene
      were compared to identify phenotypes that may be useful in diagnosing patients
      with SMS.

PMID- 21897446
TI  - Coronary artery disease in Alstrom syndrome.
AB  - Alstrom syndrome (ALMS) is a rare autosomal recessive condition, caused by
      mutations in the ALMS1 gene located on the short arm of chromosome 2. This gene
      codes for a protein linked with the centrosome, whose precise function is
      unknown. This condition was first described by Alstrom in 1959. ALMS is a
      multisystem condition that is characterised by childhood onset of blindness
      secondary to rod-cone retinal degeneration and dilated cardiomyopathy with heart
      failure, which often presents in infanthood and may recur later in life.
      Metabolic abnormalities including hypertriglyceridemia, liver steatosis, insulin
      resistance and type 2 diabetes mellitus are common, often occurring in
      association with obesity. Other abnormalities include endocrinological
      disturbances, such as thyroid disorder, growth hormone deficiency, hypogonadism
      and, in women, hyperandrogenism. This syndrome is also associated with
      sensorineural hearing loss, renal failure secondary to glomerulo-fibrosis, and
      fibrotic lung disease. Multiorgan fibrotic infiltration is the common feature in
      all cases. Considering the history of diabetes, hypertension, dyslipidemia,
      obesity and renal dysfunction in ALMS, it would be expected that this group of
      patients could develop coronary artery disease (CAD). But such cases have not
      been reported so far. We report a case of premature onset of CAD in one of the
      longest surviving patient with ALMS.

PMID- 21897447
TI  - Genome-wide homozygosity and multiple sclerosis in Orkney and Shetland Islanders.
AB  - There is strong evidence for both genetic and environmental risk factors
      comprising the aetiology of multiple sclerosis (MS). While much progress has been
      made in recent years in identifying common genetic variants using genome-wide
      association studies, alternative approaches have remained relatively neglected.
      The prevalence of MS in Orkney and Shetland is among the highest in the world.
      Previous studies have suggested that a higher degree of parental relatedness in
      these isolated communities may contribute to the high rates of MS, indicating
      that recessive effects have an important role in MS aetiology. The Northern Isles
      Multiple Sclerosis (NIMS) study investigated the potential role of genome-wide
      homozygosity in MS risk by genotyping 88 MS patients, 89 controls matched by age,
      sex and ancestry, and a further 89 controls matched for sex and ancestry, but
      passed the majority of lifetime risk of developing MS (>70 years of age). Three
      participants were removed on the basis of pedigree-genomic anomalies (n=263).
      Three measures of genome-wide homozygosity were generated for each individual,
      and association with MS was assessed using logistic regression models. No effect
      of genome-wide homozygosity was detected, indicating that inbreeding and
      consanguinity are not risk factors for MS in this population.

PMID- 21897448
TI  - Clinical utility gene card for: Mayer-Rokitansky-Kuster-Hauser syndrome.

PMID- 21897452
TI  - A 7-year-old with pulmonary hypertension.
AB  - The authors discuss the case of a 7-year-old female who presented with exertional
      cyanosis and was found to have pulmonary arterial hypertension. Despite normal
      left-sided heart function, the patient developed pulmonary oedema in response to
      pulmonary vasodilator therapy, increasing suspicion for pathology in the
      pulmonary capillaries and veins. Lung biopsy confirmed a diagnosis of pulmonary
      capillary haemangiomatosis (PCH), a rare cause of pulmonary hypertension in both
      children and adults. The diagnosis requires lung biopsy and is often made
      postmortem. She was treated with interferon alpha-2a and doxycycline for their
      antiangiogenic properties and reports of disease regression. Although she
      initially demonstrated improvement in her pulmonary hypertension in response to
      these medications, she succumbed to the disease within the time frame previously
      reported for PCH.

PMID- 21897453
TI  - Polypharmacy versus drug combinations.

PMID- 21897454
TI  - The prevention of alcohol-related problems.

PMID- 21897455
TI  - Knowledge and attitude about psychiatric illness among interns.
AB  - 58 subjects doing their compulsory rotating internship were evaluated on their
      knowledge and attitude to psychiatric illness using a multiple choice
      questionnaire, case history vignettes and an open ended attitude questionnaire.
      All of them had had a series of lectures and 4 weeks clinical posting 3 years
      prior to evaluation and weekly ethics for 3 months in the year before.It is seen
      that they have an adequate knowledge of the theoretical aspects of psychiatry,
      including the ability to diagnose. Management skills are not however
      .satisfactory. Psychiatry tanked fifth in the overall order of importance in
      terms of interest and future applicability, and only 4(6.9%) had heard of the
      National Mental Health Programme or its objectives. The results are discussed.

PMID- 21897456
TI  - Emg biofeedback ii: the dose-response relationship.
AB  - 36 clients with anxiety neurosis were trained to reduce frontalis muscle tension
      over two phases of ten sessions each. They were assessed on psychological and
      physiological measures, before, during and after the phases. The data analysis
      indicated that the clients succeeded in lowering frontalis muscle tension levels
      during the feedback and no-feedback phases of the training sessions. The inter
      correlations among the outcome measures indicated that with an increasing amount
      of control of muscle tensior, the clients perceived greater amounts of change in
      state anxiety and in anxiety symptoms. This implies that EMG biofeedback can
      effect cognitive changes in clients.

PMID- 21897457
TI  - Agnihotra in the treatment of alcoholism.
AB  - Agnihotra is a Vedic ritual of litting fire in a copper pyramid pot with use of
      Mantras at sunrise and sunset time. It is found to have neurophysiological effect
      on human body and brain. Clinically it produces mental tranquility and reported
      to have useful adjunct effect on deaddiction. In our present study effect of
      Agnihotra was studied on 18 cases of alcoholism. It is found that it leads to
      total abstinence without other restrain after 2 weeks of continuous Agnihotra
      practice. An obsessive compliance to perform Agnihotra develops. After
      discontinuing, its effect last for another few weeks. Though relapse may develop
      on discontinuing Agnihotra, a sizeable number of cases i.e. 55%, continued to
      remain abstinent for more than 8 weeks. Agnihotra is not a total cure for
      alcoholism, but it may serve as an useful adjunct.

PMID- 21897458
TI  - Prediction of outcome in schizophrenia using the subjective response to a test
      dose of a neuroleptic.
AB  - Twenty four patients meeting R.D.C. criteria for schizophrenia were assessed
      using the B.P.R.S. before starting neuroleptics. They were then given a
      standardized test dose of haloperidol. Their subjective response to the test dose
      was assessed 4 hours later by a blind rater. The B.P.R.S. ratings were repeated
      after 3 weeks of neuroleptic treatment. A dysphoric response to the test dose was
      associated with a poor therapeutic outcome. The implications of these findings
      are discussed.

PMID- 21897459
TI  - Case report: scondary mania following encephalitis : neuropsychological findings
      and diagnostic issues.
AB  - A 12 year old boy presented with the clinical picture of secondary mania.
      Neuropsychological examination revealed significant prefrontal disturbance. The
      overlap in the clinical presentation of secondary mania and frontal lobe
      syndromes is highlighted. At least some of the so called frontal lobe syndromes
      can he considered as secondary mania.

PMID- 21897460
TI  - Meditation versus medication.

PMID- 21897461
TI  - Mental health programme : need for redemption.

PMID- 21897462
TI  - Meditation from a mental health prospective.
AB  - The term "Meditation" is defined and the aims of meditation-practice are
      outlined. The physiological and psychological correlates of meditation, as found
      in different studies, are described. The need for an integrated approach to the
      study of consciousness is emphasized. The clinical applications of meditation
      practice are spelt out. Areas of further research are indicated.

PMID- 21897463
TI  - A clinical and behavioural study of hiv infected subjects-a comparison with std
      subjects.
AB  - EIGHTYFIVE HIV SEROPOSITIVE SUBJECTS (M: 42;F:43) were compared with an equal
      number STD subjects negative for HIV. They formed 1.6% of the total number (N
      =5287) screened in the STD OP. Heterosexual transmission was predominant. A
      significantly higher promiscuity and a larger number of sex partners and contacts
      were observed in the female but not the male HIV subjects. The ages at first
      coital experience were similar in both the groups. There was no difference in the
      occurrence of either STDs or psychiatric illness at index examination between the
      two groups. The symptom profile of psychiatric illness in the HIV subjects did
      not differ from that of the controls. The HIV subjects had more of physical
      diagnoses than the controls. The psychological responses to the 'disclosure' of
      seropositivity were noted. The closeness of HIV and STD groups on many factors
      and its implication for management and health education are commented upon.

PMID- 21897464
TI  - A double-blind evaluation of alprazolam and imipramine in the treatment of major
      depression.
AB  - This report describes the results of a multicentre collaborative study comparing
      the safety and efficacy of alprazolam with imipramine in patients suffering from
      major depressive disorder. Two hundred and eight patients diagnosed as major
      depression as per DSM-III criteria were randomly allocated to alprazolam (N= 105)
      or imipramine (N = 103) in a double-blind fashion. Detailed assessments were
      carried out for a period of six weeks. Results revealed that alprazolam was as
      effective as imipramine as an antidepressant. Side effects were less frequently
      reported with alprazolam.

PMID- 21897465
TI  - Pharmacokinetics of nitroxazepine in depressed patients.
AB  - A pharmacokinetic study was done on 10 depressed patients (DSM-III-R 296.3). The
      patients were treated with Sintamil (R) (nitroxazepine HCl) with titrated dose
      from 75 mg to 225 mg for 6 weeks. Plasma levels of nitroxazepine (Sintamil (R))
      and its metabolites desmethyl (D), N-oxide (N-O) and carboxylic acid (c) were
      estimated. Anti-depressant efficacy was judged by reduction in Hamilton Rating
      Depression Scale (HDRS) scores, and tolerability was monitored by reports of
      unwanted effects.The overall reduction in HDRS score was about 50% by 6 weeks.
      The plasma levels of nitroxazepin (ng/ral) showed a rise from a mean ( +SEM)
      level. 47.0 4-7.3 on day 1 (dose 75 mg) to 129.84-24.6 on day 7 (dose 150 mg) (p<
      0.01) and remained steady till day 21. There were large interindividual
      variations. The metabolites followed a similar pattern. The HDRS score showed a
      steady reduction between day 14 and 42 when the levels of nitroxizepine and des
      methyl metabolites were maintained between 176.5 ng/ml to 251 ng/ml.

PMID- 21897466
TI  - Autism in tuberous sclerosis.
AB  - A case of Tuberous Sclerosis with infantile autism, misdiagnosed as mental
      retardation with seizure disorder is being discussed in light of the implication
      of the misdiagnosis.

PMID- 21897467
TI  - Catatonia and hyponatremia : a case report.
AB  - We report a case of recurrent mania who developed catatonia and was found to be
      markedly hyponatraemia. The catatonic symptoms showed rapid resolution following
      correction of hyponatraemia suggesting a causal link between the two. It is
      suggested that the estimation of serum electrolyte levels should be an important
      part of the evaluation of cases of catatonia.

PMID- 21897468
TI  - A clinical study of chronic depression.
AB  - Neurological status of chronic depressive states have not been resolved as yet.
      Recent classificatory systems ICD-X and DSM-III-R have included chronic
      depression under affective disorders and have done away with the category of
      neurotic depression. The present study was undertaken with the aims of (a) to
      study clinical variables associated with major subtypes of chronic depression
      (chronic major depression and dysthymia) and (b) to investigate personality
      characteristics and life events associated with major subtypes of chronic
      depression. The sample was drawn from outpatients and inpatients as per DSM-DI-R
      criteria. 30 patients were studied (21 chronic major depression and 9 dysthymia).
      They were administered Hamilton Depression Rating Scale, Eysenck Personality
      Inventory and Interview for recent life event (Paykel and Mangen, 1980) and
      details of sociodemographic and clinical variables were recorded. Symptomatically
      dysthymia and chronic major depression are indistinguishable. More patients of
      dysthymia have positive family history of depressive disorder. Dysthymia had
      significantly higher score on neuroticism. All chronic depressives tend to report
      more life stresses during the courses of illness.

PMID- 21897469
TI  - Simple schizophrenia :patients in search of a diagnosis.
AB  - Recent classification systems of schizophrenia consider the presence of psychotic
      features like certain forms of hallucinations and delusions as sine qua non of
      this disorder. Consequently, earlier categories like simple schizophrenia have
      been discarded from many diagnostic systems. However, there is a category of
      patients who present with gross deterioration in personality without ever
      experiencing hallucinations or delusions. Negative schizophrenia, a contemporary
      popular syndrome has again revived interest in this subgroup of patients. The
      authors present four cases diagnosed as simple schizophrenia and argue the case
      for retention of this subgroup of schizophrenia in the current nosological
      classification systems and conclude that simple schizophrenia of yesteryears has
      close resemblance with today's negative schizophrenia.

PMID- 21897470
TI  - Clinical variables and platelet mao in schizophrenia.
AB  - Platelet MAO activity was estimated in 60 male drug free schizophrenics and 26
      controls matched for age. The paranoid group had significantly lower enzyme
      activity than the non-paranoid group and controls. Patients with premorbid
      schizoid personality had significantly lower enzyme activity than patients with
      non-schizoid premorbid personality and controls. A significant negative
      correlation between platelet MAO activity and severity and duration of illness
      was observed. Family history of schizophrenia, presence of auditory
      hallucinations and type and age of onset of illness were not related to platelet
      MAO activity.

PMID- 21897471
TI  - Maintenance therapy for hospital out-patients.
AB  - A study of dosage requirements undertaken among chronic OPD patients found on
      unnecessarily high drug dosage regimes. Basing on OPD experiences authors discuss
      long term treatment strategies and strongly advocate low dose intermittent oral
      therapy.

PMID- 21897472
TI  - Alcoholism and psoriasis-an immunological relationship.
AB  - Studies on association of psychiatric diseases and immunopathology has been an
      area of recent research activities. Alcohol has been implicated in some immune
      mediated disorders. Observation of occurrence of psoriasis, an immune mediated
      skin disorder in alcoholic patients has not been reported anywhere in literature.
      We report here 4 cases of alcoholism related psoriasis and discuss the possible
      immunological relationship between these two disorders. The need for study of
      effect of alcoholism on cell-medicated immunity associated conditions like auto
      immune disorders and malignancy is presented.

PMID- 21897473
TI  - Psychopathology of confabulations in head injury.
AB  - Confabulations observed during head injury recovery were of two types ; momentary
      and fantastic. Both occurred in relation to either the dysmnestic phase of early
      recovery or the post traumatic amnesic syndrome. In a follow-up of 174 head
      injured patients, all 12 patients evincing confabulations had suffered from
      acceleration injuries. In comparison to controls, they had a longer post
      traumatic amnesia period. Clinical and psychometric lateralization of the
      deficits pointed to left sided impairment. Their memory scores were not
      qualitatively or quantitatively different from those of equivalent controls.
      Patients differed from the controls in certain personality dimensions. Relative
      contribution of clinical deficits, memory impairment and personality dimensions
      to the occurrence of confabulations and its dynamic significance in maintaining
      the personal identity system of the patient are discussed.

PMID- 21897474
TI  - Meditation from an Indian perspective.

PMID- 21897477
TI  - Remind me again: why are we here?

PMID- 21897478
TI  - The psychosocial response to the 2011 Tohoku earthquake.

PMID- 21897480
TI  - Unlocking the power of books for people with disabilities.

PMID- 21897481
TI  - Screening still the "best buy" for tackling cervical cancer.

PMID- 21897482
TI  - Sitting with the women under the trees.

PMID- 21897483
TI  - Electronic monitoring of treatment adherence and validation of alternative
      adherence measures in tuberculosis patients: a pilot study.
AB  - OBJECTIVE: To assess adherence to community-based directly observed treatment
      (DOT) among Tanzanian tuberculosis patients using the Medication Event Monitoring
      System (MEMS) and to validate alternative adherence measures for resource-limited
      settings using MEMS as a gold standard. METHODS: This was a longitudinal pilot
      study of 50 patients recruited consecutively from one rural hospital, one urban
      hospital and two urban health centres. Treatment adherence was monitored with
      MEMS and the validity of the following adherence measures was assessed: isoniazid
      urine test, urine colour test, Morisky scale, Brief Medication Questionnaire,
      adapted AIDS Clinical Trials Group (ACTG) adherence questionnaire, pill counts
      and medication refill visits. FINDINGS: The mean adherence rate in the study
      population was 96.3% (standard deviation, SD: 7.7). Adherence was less than 100%
      in 70% of the patients, less than 95% in 21% of them, and less than 80% in 2%.
      The ACTG adherence questionnaire and urine colour test had the highest
      sensitivities but lowest specificities. The Morisky scale and refill visits had
      the highest specificities but lowest sensitivities. Pill counts and refill visits
      combined, used in routine practice, yielded moderate sensitivity and specificity,
      but sensitivity improved when the ACTG adherence questionnaire was added.
      CONCLUSION: Patients on community-based DOT showed good adherence in this study.
      The combination of pill counts, refill visits and the ACTG adherence
      questionnaire could be used to monitor adherence in settings where MEMS is not
      affordable. The findings with regard to adherence and to the validity of simple
      adherence measures should be confirmed in larger populations with wider
      variability in adherence rates.

PMID- 21897484
TI  - Sensitivity and specificity of typhoid fever rapid antibody tests for laboratory
      diagnosis at two sub-Saharan African sites.
AB  - OBJECTIVE: To evaluate three commercial typhoid rapid antibody tests for
      Salmonella Typhi antibodies in patients suspected of having typhoid fever in
      Mpumalanga, South Africa, and Moshi, United Republic of Tanzania. METHODS: The
      diagnostic accuracy of Cromotest((r)) (semiquantitative slide agglutination and
      single tube Widal test), TUBEX((r)) and Typhidot((r)) was assessed against that
      of blood culture. Performance was modelled for scenarios with pretest
      probabilities of 5% and 50%. FINDINGS: In total 92 patients enrolled: 53 (57.6%)
      from South Africa and 39 (42.4%) from the United Republic of Tanzania. Salmonella
      Typhi was isolated from the blood of 28 (30.4%) patients. The semiquantitative
      slide agglutination and single-tube Widal tests had positive predictive values
      (PPVs) of 25.0% (95% confidence interval, CI: 0.6-80.6) and 20.0% (95% CI: 2.5
      55.6), respectively. The newer typhoid rapid antibody tests had comparable PPVs:
      TUBEX((r)), 54.1% (95% CI: 36.9-70.5); Typhidot((r)) IgM, 56.7% (95% CI: 37.4
      74.5); and Typhidot((r)) IgG, 54.3% (95% CI: 36.6-71.2). For a pretest
      probability of 5%, PPVs were: TUBEX((r)), 11.0% (95% CI: 6.6-17.9); Typhidot((r))
      IgM, 9.1% (95% CI: 5.8-14.0); and Typhidot((r)) IgG, 11.0% (6.3-18.4). For a
      pretest probability of 50%, PPVs were: TUBEX((r)), 70.2% (95% CI: 57.3-80.5);
      Typhidot((r)) IgM, 65.6% (95% CI: 54.0-75.6); and Typhidot((r)) IgG, 70.0% (95%
      CI: 56.0-81.1). CONCLUSION: Semiquantitative slide agglutination and single-tube
      Widal tests performed poorly. TUBEX((r)) and Typhidot((r)) may be suitable when
      pretest probability is high and blood cultures are unavailable, but their
      performance does not justify deployment in routine care settings in sub-Saharan
      Africa.

PMID- 21897485
TI  - Cardiovascular disease prevention in Ghana: feasibility of a faith-based
      organizational approach.
AB  - OBJECTIVE: To examine the feasibility of using community health workers (CHWs) to
      implement cardiovascular disease (CVD) prevention programmes within faith-based
      organizations in Accra, Ghana. METHODS: Faith-based organization capacity, human
      resources, health programme sustainability/barriers and community members'
      knowledge were evaluated. Data on these aspects were gathered through a mixed
      method design consisting of in-depth interviews and focus groups with 25 church
      leaders and health committee members from five churches, and of a survey of 167
      adult congregants from two churches. FINDINGS: The delivery of a CVD prevention
      programme in faith-based organizations by CHWs is feasible. Many faith-based
      organizations already provide health programmes for congregants and involve non
      health professionals in their health-care activities, and most congregants have a
      basic knowledge of CVD. Yet despite the feasibility of the proposed approach to
      CVD prevention through faith-based organizations, sociocultural and health-care
      barriers such as poverty, limited human and economic resources and limited access
      to health care could hinder programme implementation. CONCLUSION: The barriers to
      implementation identified in this study need to be considered when defining CVD
      prevention programme policy and planning.

PMID- 21897486
TI  - Elective induction versus spontaneous labour in Latin America.
AB  - OBJECTIVE: To assess the frequency of elective induction of labour and its
      determinants in selected Latin America countries; quantify success in attaining
      vaginal delivery, and compare rates of caesarean and adverse maternal and
      perinatal outcomes after elective induction versus spontaneous labour in low-risk
      pregnancies. METHODS: Of 37,444 deliveries in women with low-risk pregnancies,
      1847 (4.9%) were electively induced. The factors associated with adverse maternal
      and perinatal outcomes among cases of spontaneous and induced onset of labour
      were compared. Odds ratios for factors potentially associated with adverse
      outcomes were calculated, as were the relative risks of having an adverse
      maternal or perinatal outcome (both with their 95% confidence intervals).
      Adjustment using multiple logistic regression models followed these analyses.
      FINDINGS: Of 11,077 cases of induced labour, 1847 (16.7%) were elective. Elective
      inductions occurred in 4.9% of women with low-risk pregnancies (37,444). Oxytocin
      was the most common method used (83% of cases), either alone or combined with
      another. Of induced deliveries, 88.2% were vaginal. The most common maternal
      adverse events were: (i) a higher postpartum need for uterotonic drugs, (ii) a
      nearly threefold risk of admission to the intensive care unit; (iii) a fivefold
      risk of postpartum hysterectomy, and (iv) an increased need for
      anaesthesia/analgesia. Perinatal outcomes were satisfactory except for a 22%
      higher risk of delayed breastfeeding (i.e. initiation between 1 hour and 7 days
      postpartum). CONCLUSION: Caution is mandatory when indicating elective labour
      induction because the increased risk of maternal and perinatal adverse outcomes
      is not outweighed by clear benefits.

PMID- 21897487
TI  - The impact of adolescent pertussis immunization, 2004-2009: lessons from
      Australia.
AB  - OBJECTIVE: To compare the impact of three strategies for delivering a booster
      dose of adult-formulated tetanus-diphtheria-pertussis (Tdap) vaccine to
      adolescents in Australia. These comprise: (i) administering Tdap to: a one-year
      age cohort; (ii) administering Tdap to the entire high school and to subsequent
      entrant cohorts; and (iii) administering Tdap to the entire high school but
      without continuing to immunize entrant cohorts. METHODS: A series of ecologic
      analyses of pertussis notifications during epidemic periods in relevant age
      cohorts were conducted. The primary outcome measure was the incidence rate ratio
      (IRR), calculated by dividing pertussis incidence after the introduction of Tdap
      delivery programmes by pertussis incidence during the most recent pre-programme
      epidemic. FINDINGS: During the epidemic period of 2008-2009, the national-level
      IRR among age cohorts targeted for Tdap was 0.6 (95% confidence interval, CI: 0.6
      0.7), but among other age cohorts it was 1.1 (95% CI: 1.1-1.2). Only the
      jurisdiction that implemented strategy 2 (Western Australia) experienced
      sustained decreases in pertussis notifications in both adolescents and infants
      under 6 months of age (IRR: 0.4; 95% CI: 0.3-0.6) until 2009. CONCLUSION: If
      confirmed by longer experience in Australia and elsewhere, a broad school-based
      catch-up programme followed by immunization of school entrants may be the optimum
      strategy for the implementation of adolescent Tdap programmes.

PMID- 21897489
TI  - Meeting global health challenges through operational research and management
      science.
AB  - This paper considers how operational research and management science can improve
      the design of health systems and the delivery of health care, particularly in low
      resource settings. It identifies some gaps in the way operational research is
      typically used in global health and proposes steps to bridge them. It then
      outlines some analytical tools of operational research and management science and
      illustrates how their use can inform some typical design and delivery challenges
      in global health. The paper concludes by considering factors that will increase
      and improve the contribution of operational research and management science to
      global health.

PMID- 21897488
TI  - A point-of-care test for measles diagnosis: detection of measles-specific IgM
      antibodies and viral nucleic acid.
AB  - OBJECTIVE: To evaluate the performance of a newly developed point-of-care test
      (POCT) for the detection of measles-specific IgM antibodies in serum and oral
      fluid specimens and to assess if measles virus nucleic acid could be recovered
      from used POCT strips. METHODS: The POCT was used to test 170 serum specimens
      collected through measles surveillance or vaccination programmes in Ethiopia,
      Malaysia and the Russian Federation: 69 were positive for measles immunoglobulin
      M (IgM) antibodies, 74 were positive for rubella IgM antibodies and 7 were
      positive for both. Also tested were 282 oral fluid specimens from the measles,
      mumps and rubella (MMR) surveillance programme of the United Kingdom of Great
      Britain and Northern Ireland. The Microimmune measles IgM capture enzyme
      immunoassay was the gold standard for comparison. A panel of 24 oral fluids was
      used to investigate if measles virus haemagglutinin (H) and nucleocapsid (N)
      genes could be amplified by polymerase chain reaction directly from used POCT
      strips. FINDINGS: With serum POCT showed a sensitivity and specificity of 90.8%
      (69/76) and 93.6% (88/94), respectively; with oral fluids, sensitivity and
      specificity were 90.0% (63/70) and 96.2% (200/208), respectively. Both H and N
      genes were reliably detected in POCT strips and the N genes could be sequenced
      for genotyping. Measles virus genes could be recovered from POCT strips after
      storage for 5 weeks at 20-25  degrees C. CONCLUSION: The POCT has the sensitivity
      and specificity required of a field-based test for measles diagnosis. However,
      its role in global measles control programmes requires further evaluation.

PMID- 21897490
TI  - Imprisonment and women's health: concerns about gender sensitivity, human rights
      and public health.
AB  - The health of prisoners is among the poorest of any population group and the
      apparent inequalities pose both a challenge and an opportunity for country health
      systems. The high rates of imprisonment in many countries, the resulting
      overcrowding, characteristics of prison populations and the disproportionate
      prevalence of health problems in prison should make prison health a matter of
      public health importance.Women prisoners constitute a minority within all prison
      systems and their special health needs are frequently neglected. The urgent need
      to review current services is clear from research, expert opinion and experience
      from countries worldwide. Current provision of health care to imprisoned women
      fails to meet their needs and is, in too many cases, far short of what is
      required by human rights and international recommendations. The evidence includes
      a lack of gender sensitivity in policies and practices in prisons, violations of
      women's human rights and failure to accept that imprisoned women have more and
      different health-care needs compared with male prisoners, often related to
      reproductive health issues, mental health problems, drug dependencies and
      histories of violence and abuse. Additional needs stem from their frequent status
      as a mother and usually the primary carer for her children.National governments,
      policy-makers and prison management need to address gender insensitivity and
      social injustice in prisons. There are immediate steps which could be taken to
      deal with public health neglect, abuses of human rights and failures in gender
      sensitivity.

PMID- 21897491
TI  - Can performance-based financing be used to reform health systems in developing
      countries?
AB  - Over the past 15 years, performance-based financing has been implemented in an
      increasing number of developing countries, particularly in Africa, as a means of
      improving health worker performance. Scaling up to national implementation in
      Burundi and Rwanda has encouraged proponents of performance-based financing to
      view it as more than a financing mechanism, but increasingly as a strategic tool
      to reform the health sector. We resist such a notion on the grounds that results
      based and economically driven interventions do not, on their own, adequately
      respond to patient and community needs, upon which health system reform should be
      based. We also think the debate surrounding performance-based financing is biased
      by insufficient and unsubstantiated evidence that does not adequately take
      account of context nor disentangle the various elements of the performance-based
      financing package.

PMID- 21897492
TI  - Performance-based financing: the need for more research.

PMID- 21897493
TI  - Looking at the effects of performance-based financing through a complex adaptive
      systems lens.

PMID- 21897494
TI  - Why there is so much enthusiasm for performance-based financing, particularly in
      developing countries.

PMID- 21897495
TI  - Trends in the Educational Gradient of U.S. Adult Mortality from 1986 to 2006 by
      Race, Gender, and Age Group.
AB  - The educational gradient of U.S. adult mortality became steeper between 1960 and
      the mid 1980s, but whether it continued to steepen is less clear given a dearth
      of attention to these trends since that time. This study provides new evidence on
      trends in the education-mortality gradient from 1986 to 2006 by race, gender, and
      age among non-Hispanic whites and blacks using data from the 2010 release of the
      National Health Interview Survey Linked Mortality File. Results show that, for
      white and black men, the gradient steepened among older ages because declines in
      mortality risk across education levels were greater among the higher educated.
      The gradient steepened among white women, and to a much lesser and only
      marginally significant extent among black women, largely because mortality risk
      decreased among the college-educated but increased among women with less than a
      high school degree. Greater returns to higher education and compositional changes
      within educational strata likely contributed to the trends.

PMID- 21897497
TI  - Fospropofol: Is there an infusion regimen for propofol equivalence?

PMID- 21897374
TI  - Measurement of the inelastic proton-proton cross-section at ?s=7 TeV with the
      ATLAS detector.
AB  - The dependence of the rate of proton-proton interactions on the centre-of-mass
      collision energy, ?s, is of fundamental importance for both hadron collider
      physics and particle astrophysics. The dependence cannot yet be calculated from
      first principles; therefore, experimental measurements are needed. Here we
      present the first measurement of the inelastic proton-proton interaction cross
      section at a centre-of-mass energy, ?s, of 7 TeV using the ATLAS detector at the
      Large Hadron Collider. Events are selected by requiring hits on scintillation
      counters mounted in the forward region of the detector. An inelastic cross
      section of 60.3 +/- 2.1 mb is measured for xi > 5*10-6, where xi is calculated
      from the invariant mass, M(X), of hadrons selected using the largest rapidity gap
      in the event. For diffractive events, this corresponds to requiring at least one
      of the dissociation masses to be larger than 15.7 GeV.

PMID- 21897496
TI  - Dexmedetomidine: New avenues.

PMID- 21897498
TI  - Pregabalin in acute and chronic pain.
AB  - Pregabalin is a gamma-amino-butyric acid analog shown to be effective in several
      models of neuropathic pain, incisional injury, and inflammatory injury. In this
      review, the role of pregabalin in acute postoperative pain and in chronic pain
      syndromes has been discussed. Multimodal perioperative analgesia with the use of
      gabapentinoids has become common. Based on available evidence from randomized
      controlled trials and meta-analysis, the perioperative administration of
      pregabalin reduces opioid consumption and opioid-related adverse effects in the
      first 24 h following surgery. Postoperative pain intensity is however not
      consistently reduced by pregabalin. Adverse effects like visual disturbance,
      sedation, dizziness, and headache are associated with higher doses. The advantage
      of the perioperative use of pregabalin is so far limited to laparoscopic,
      gynecological, and daycare surgeries which are not very painful. The role of the
      perioperative administration of pregabalin in preventing chronic pain following
      surgery, its efficacy in more painful surgeries and surgeries done under regional
      anesthesia, and the optimal dosage and duration of perioperative pregabalin need
      to be studied. The efficacy of pregabalin in chronic pain conditions like painful
      diabetic neuropathy, postherpetic neuralgia, central neuropathic pain, and
      fibromyalgia has been demonstrated.

PMID- 21897499
TI  - Anesthesia for joint replacement surgery: Issues with coexisting diseases.
AB  - The first joint replacement surgery was performed in 1919. Since then, joint
      replacement surgery has undergone tremendous development in terms of surgical
      technique and anesthetic management. In this era of nuclear family and
      independent survival, physical mobility is of paramount importance. In recent
      years, with an increase in life expectancy, advances in geriatric medicine and
      better insurance coverage, the scenario of joint replacement surgery has changed
      significantly. Increasing number of young patients are undergoing joint
      replacement for pathologies like rheumatoid arthritis and ankylosing spondylitis.
      The diverse pathologies and wide range of patient population brings unique
      challenges for the anesthesiologist. This article deals with anesthetic issues in
      joint replacement surgery in patients with comorbidities.

PMID- 21897503
TI  - Ultrasound-guided continuous transverse abdominis plane block for abdominal
      surgery.

PMID- 21897501
TI  - Comparison of total intravenous anesthesia using propofol and inhalational
      anesthesia using isoflurane for controlled hypotension in functional endoscopic
      sinus surgery.
AB  - BACKGROUND: An important requirement during functional endoscopic sinus surgery
      is to maintain a clear operative field to improve visualization during surgery
      and to minimize complications. MATERIALS AND METHODS: We compared total
      intravenous anesthesia using propofol with inhalational anesthesia using
      isoflurane for controlled hypotension in functional endoscopic sinus surgery. It
      was a prospective study in a tertiary hospital in India. Forty ASA physical
      status I and II adult patients (16-60 years) were randomly allocated to one of
      two parallel groups (isoflurane group, n = 20; propofol group, n = 20). The
      primary outcome was to know whether total intravenous anesthesia using propofol
      was superior to inhalational anesthesia using isoflurane for controlled
      hypotension. The secondary outcomes measured were intraoperative blood loss,
      duration of surgery, surgeon's opinion regarding the surgical field and the
      incidence of complications. RESULTS: The mean (+/-SD) time to achieve the target
      mean blood pressure was 18 (+/-8) minutes in the isoflurane group and 16 (+/-7)
      minutes in the propofol group (P = 0.66). There was no statistically significant
      difference (P = 0.402) between these two groups in terms of intraoperative blood
      loss and operative field conditions (P = 0.34). CONCLUSIONS: Controlled
      hypotension can be achieved equally and effectively with both propofol and
      isoflurane. Total intravenous anesthesia using propofol offers no significant
      advantage over isoflurane-based anesthetic technique in terms of operative
      conditions and blood loss.

PMID- 21897500
TI  - Clonidine as an adjunct to intravenous regional anesthesia: A randomized, double
      blind, placebo-controlled dose ranging study.
AB  - BACKGROUND: The addition of clonidine to lidocaine intravenous regional
      anesthesia (IVRA) has been previously reported to improve postoperative analgesia
      in patients undergoing upper extremity surgery. Our objective was to perform a
      dose ranging study in order to determine the optimal dose of clonidine used with
      lidocaine in IVRA. DESIGN #ENTITYSTARTX00026; SETTING: We performed a double
      blinded randomized placebo-controlled study with 60 patients scheduled for
      elective endoscopic carpal tunnel release under IVRA with 50 ml lidocaine 0.5%.
      University-affiliated outpatient surgery center. Data collected in operating
      rooms, recovery room, and by telephone after discharge from surgery center.
      MATERIALS #ENTITYSTARTX00026; METHODS: Sixty adult ASA I or II patients
      undergoing outpatient endoscopic carpal tunnel release under intravenous regional
      anesthesia.Patients were randomized into five study groups receiving different
      doses of clonidine in addition to 50 ml 0.5% lidocaine in their IVRA. Group A
      received 0 mcg/kg, group B 0.25 mcg/kg, group C 0.5 mcg/kg, group D 1.0 mcg/kg
      and group E 1.5 mcg/kg of clonidine.Intraoperative fentanyl, recovery room pain
      scores, time to first postsurgical analgesic, total number of
      acetaminophen/codeine tablets consumed postsurgery, incidence of sedation,
      hypotension and bradycardia. RESULTS #ENTITYSTARTX00026; CONCLUSIONS: There was
      no benefit from any dose of clonidine compared to placebo. There were no
      clonidine-related side effects seen within the dose range studied. In short
      duration minor hand surgery, the addition of clonidine to lidocaine-based
      intravenous regional anesthesia provides no measurable benefit.

PMID- 21897502
TI  - Ultrasound-guided continuous transverse abdominis plane block for abdominal
      surgery.
AB  - INTRODUCTION: Transversus abdominis plane (TAP) block is a new regional analgesic
      technique for postoperative pain in abdominal surgery. Its efficacy is not clear,
      and thus it needs to be explored for its regular utilisation on prolonged period.
      The objective was to study the continuous local anaesthetic infusion effect on
      postoperative analgesia. Continuous use of TAP block as an analgesic technique
      has not been evaluated prospectively in clinical trials. This study evaluates the
      efficacy of ultrasound-guided TAP block in comparison with PCA fentanyl in major
      abdominal surgery. MATERIALS AND METHODS: There were 20 patients in the study,
      allocated to TAP and control groups. The parameters measured were pain scores on
      a numerical rating scale (NRS) of 0-10 at various time intervals and the amount
      of fentanyl used as rescue analgesia. Patient satisfaction scores were recorded
      in the TAP block group and along with any complications related to the block.
      RESULTS: The postoperative median pain scores on coughing on day one were 6.0 for
      control group and 2.0 for the TAP group (P = 0.02); on day two, the equivalent
      scores were 7.0 and 2.0 (P = 0.01). The fentanyl requirement at one hour was 203
      MU for the control group and 78 MUg for the TAP group (P = 0.03); at day one, the
      control and TAP requirements were 1237 MUg and 664 MUg respectively (P = 0.01).
      Three TAP patients rated their satisfaction as 'excellent', four as 'satisfied,
      and two as 'poor'. CONCLUSION: TAP block is a promising technique for
      postoperative analgesia in major abdominal surgeries. Our study demonstrated
      lower pain scores in the TAP group with reduced fentanyl requirement. Further, a
      large scale study is needed to establish the efficacy of TAP block in this
      setting.

PMID- 21897505
TI  - Comparative study of intravenously administered clonidine and magnesium sulfate
      on hemodynamic responses during laparoscopic cholecystectomy.
AB  - BACKGROUND: Both magnesium and clonidine are known to inhibit catecholamine and
      vasopressin release and attenuate hemodynamic response to pneumoperitoneum. This
      randomized, double blinded, placebo controlled study has been designed to assess
      which agent attenuates hemodynamic stress response to pneumoperitoneum better.
      MATERIALS AND METHODS: 120 patients undergoing elective laparoscopic
      cholecystectomy were randomized into 4 groups of 30 each. Group K patients
      received 50 ml normal saline over a period of 15 min after induction and before
      pneumoperitoneum, group M patients received 50 mg/kg of magnesium sulfate in
      normal saline (total volume 50 ml) over same time duration. Similarly group C1
      patients received 1 MUg/kg clonidine and group C2 1.5 MUg/kg clonidine
      respectively in normal saline (total volume 50 ml). Blood pressure and heart rate
      were recorded before induction (baseline value), at the end of infusions and
      every 5 min after pneumoperitoneum. STATISTICAL ANALYSIS: Paired t test was used
      for intra-group comparison and ANOVA for inter-group comparison. RESULTS:
      Systolic blood pressure was significantly higher in control group as compared to
      all other groups during pneumoperitoneum. On comparing patients in group M and
      group C1, no significant difference in systolic BP was found at any time
      interval. Patients in group C2 showed best control of systolic BP. As compared to
      group M and group C1, BP was significantly lower at 10, 30 and 40 min post
      pneumoperitoneum. No significant episodes of hypotension were found in any of the
      groups. Extubation time and time to response to verbal command like eye opening
      was significantly longer in group M as compared to other groups. CONCLUSION:
      Administration of magnesium sulfate or clonidine attenuates hemodynamic response
      to pneumoperitoneum. Although magnesium sulfate 50 mg/kg produces hemodynamic
      stability comparable to clonidine 1 MUg/kg, clonidine in doses of 1.5MUg/kg
      blunts the hemodynamic response to pneumoperitoneum more effectively.

PMID- 21897504
TI  - A Comparative study of intrathecal dexmedetomidine and fentanyl as adjuvants to
      Bupivacaine.
AB  - BACKGROUND: Various adjuvants have been used with local anesthetics in spinal
      anesthesia to avoid intraoperative visceral and somatic pain and to provide
      prolonged postoperative analgesia. Dexmedetomidine, the new highly selective
      alpha2-agonist drug, is now being used as a neuraxial adjuvant. The aim of this
      study was to evaluate the onset and duration of sensory and motor block,
      hemodynamic effect, postoperative analgesia, and adverse effects of
      dexmedetomidine or fentanyl given intrathecally with hyperbaric 0.5% bupivacaine.
      MATERIALS AND METHODS: Sixty patients classified in American Society of
      Anesthesiologists classes I and II scheduled for lower abdominal surgeries were
      studied. Patients were randomly allocated to receive either 12.5 mg hyperbaric
      bupivacaine plus 5 MUg dexmedetomidine (group D, n = 30) or 12.5 mg hyperbaric
      bupivacaine plus 25 MUg fentanyl (group F, n = 30) intrathecal. RESULTS: Patients
      in dexmedetomidine group (D) had a significantly longer sensory and motor block
      time than patients in fentanyl group (F). The mean time of sensory regression to
      S1 was 476+/-23 min in group D and 187+/-12 min in group F (P<0.001). The
      regression time of motor block to reach modified Bromage 0 was 421+/-21 min in
      group D and 149+/-18 min in group F (P<0.001). CONCLUSIONS: Intrathecal
      dexmedetomidine is associated with prolonged motor and sensory block, hemodynamic
      stability, and reduced demand for rescue analgesics in 24 h as compared to
      fentanyl.

PMID- 21897506
TI  - Pre-induction low dose pethidine does not decrease incidence of postoperative
      shivering in laparoscopic gynecological surgeries.
AB  - OBJECTIVES: The incidence of shivering in patients undergoing a laparoscopic
      procedure is stated to be about 40%. A majority of laparoscopic gynecological
      procedures are taken up on an outpatient basis. Postoperative shivering may delay
      hospital discharge and is a common cause of discomfort in patients recovering
      from anesthesia. AIMS: To determine the effect of pre-induction, low-dose
      pethidine on postoperative shivering in patients undergoing laparoscopic
      gynecological surgeries. SETTING AND DESIGN: Sixty females between 25 and 35
      years of age, of American Society of Anesthesiologists (ASA) class 1 and 2, were
      randomly divided into three groups of 20 patients each. Group I and II patients
      received i.v. pethidine 0.3 mg/kg and 0.5 mg/kg, respectively, while Group III
      received i.v. 0.9% normal saline just before induction of general anesthesia.
      Temperature of the Operating Room and the Post Anesthesia Care Unit was
      standardized and all fluids given during the study period were warmed to 37
      degrees C. MATERIALS AND METHODS: Temperature, measured with a tympanic membrane
      probe, was recorded preoperatively, after induction of anesthesia, on arrival at
      the Post Anesthesia Care Unit, and postoperatively at 15 minutes and 30 minutes.
      Shivering was graded (0 - 4 scale) at arrival of the patients to the PACU and
      every five minutes thereafter, up to 30 minutes. STATISTICAL ANALYSIS: ANOVA, Chi
      square test, Kruskal-Wallis ANOVA and Mann-Whitney U tests were used. A P-value
      of less than 0.05 was considered significant. RESULTS: Core body temperatures
      were statistically insignificant between groups at pre-induction, post-induction,
      and in the PACU (P > 0.05). At the end of surgery, shivering was present in 18
      patients (30%). In groups I, II, and III, six (30%), three (15%), and nine (45%)
      patients shivered, respectively. The differences in incidence and grading of
      shivering among groups was found to be statistically insignificant (P > 0.05).
      The core body temperature of shiverers and non-shiverers were compared. In the
      PACU at 0, 15, and 30 minutes, the temperature among shiverers was significantly
      lower than that in the non-shiverers. Rescue drug i.v. pethidine 20 mg was given
      to patients with shivering grade >=2. None of the patients had shivering after 10
      minutes. CONCLUSIONS: Prophylactic pre-induction, low-dose pethidine does not
      have major role in preventing postoperative shivering.

PMID- 21897507
TI  - Influence of music on operation theatre staff.
AB  - BACKGROUND AND OBJECTIVE: The purpose of the study was to evaluate the perception
      of influence of music among surgeons, anesthesiologist and nurses in our hospital
      as well as to critically evaluate whether music can be used as an aid in
      improving the work efficiency of medical personnel in the operation theatre (OT).
      MATERIALS AND METHODS: A prospective, questionnaire-based cross-sectional study
      was conducted. A total of 100 randomly selected subjects were interviewed, which
      included 44 surgeons, 25 anesthesiologists and 31 nurses. Statistical package for
      social sciences (SPSS) Windows Version 16 software was used for statistical
      evaluation. RESULTS: Most of the OT medical personnel were found to be aware of
      the beneficial effects of music, with 87% consenting to the playing of music in
      the OT. It was also found that most participants agreed to have heard music on a
      regular basis in the OT, while 17% had heard it whenever they have been to the
      OT. CONCLUSIONS: Majority of the respondent's preferred playing music in the OT
      which helped them relax. It improved the cognitive function of the listeners and
      created a sense of well being among the people and elevated mood in them. Music
      helped in reducing the autonomic reactivity of theatre personnel in stressful
      surgeries allowing them to approach their surgeries in a more thoughtful and
      relaxed manner. Qualitative, objective and comprehensive effect of specific music
      types varied with different individuals. Music can aid in improving the work
      efficiency of medical personnel in the OT. The study has reinforced the
      beneficial effects of playing music in the OT outweighing its deleterious
      outcomes.

PMID- 21897508
TI  - Endotracheal tube cuff pressure monitoring during neurosurgery - Manual vs.
      automatic method.
AB  - BACKGROUND: Inflation and assessment of the endotracheal tube cuff pressure is
      often not appreciated as a critical aspect of endotracheal intubation.
      Appropriate endotracheal tube cuff pressure, endotracheal intubation seals the
      airway to prevent aspiration and provides for positive-pressure ventilation
      without air leak. MATERIALS AND METHODS: Correlations between manual methods of
      assessing the pressure by an experienced anesthesiologists and assessment with
      maintenance of the pressure within the normal range by the automated pressure
      controller device were studied in 100 patients divided into two groups. In Group
      M, endotracheal tube cuff was inflated manually by a trained anesthesiologist and
      checked for its pressure hourly by cuff pressure monitor till the end of surgery.
      In Group C, endotracheal tube cuff was inflated by automated cuff pressure
      controller and pressure was maintained at 25-cm H(2)O throughout the surgeries.
      Repeated measure ANOVA was applied. RESULTS: Repeated measure ANOVA results
      showed that average of endotracheal tube cuff pressure of 50 patients taken at
      seven different points is significantly different (F-value: 171.102, P-value:
      0.000). Bonferroni correction test shows that average of endotracheal tube cuff
      pressure in all six groups are significantly different from constant group (P =
      0.000). No case of laryngomalacia, tracheomalacia, tracheal stenosis,
      tracheoesophageal fistula or aspiration pneumonitis was observed. CONCLUSIONS:
      Endotracheal tube cuff pressure was significantly high when endotracheal tube
      cuff was inflated manually. The known complications of high endotracheal tube
      cuff pressure can be avoided if the cuff pressure controller device is used and
      manual methods cannot be relied upon for keeping the pressure within the
      recommended levels.

PMID- 21897509
TI  - Anesthetic complications including two cases of postoperative respiratory
      depression in living liver donor surgery.
AB  - BACKGROUND: Living liver donation is becoming a more common means to treat
      patients with liver failure because of a shortage of cadaveric organs and
      tissues. There is a potential for morbidity and mortality, however, in patients
      who donate a portion of their liver. The purpose of this study is to identify
      anesthetic complications and morbidity resulting from living liver donor surgery.
      PATIENTS AND METHODS: The anesthetic records of all patients who donated a
      segment of their liver between January 1997 and January 2006 at University of
      Minnesota Medical Center-Fairview were retrospectively reviewed. The surgical and
      anesthesia time, blood loss, hospitalization length, complications, morbidity,
      and mortality were recorded. Data were reported as absolute values, mean +/- SD,
      or percentage. Significance (P < 0.05) was determined using Student's paired t
      tests. RESULTS: Seventy-four patients (34 male, 40 female, mean age = 35.5 +/-
      9.8 years) donated a portion of their liver and were reviewed in the study. Fifty
      seven patients (77%) donated the right hepatic lobe, while 17 (23%) donated a
      left hepatic segment. The average surgical time for all patients was 7.8 +/- 1.5
      hours, the anesthesia time was 9.0 +/- 1.3 hours, and the blood loss was 423 +/-
      253 ml. Forty-six patients (62.2%) received autologous blood either from a cell
      saver or at the end of surgery following acute, normovolemic hemodilution, but
      none required an allogenic transfusion. Two patients were admitted to the
      intensive care unit due to respiratory depression. Both patients donated their
      right hepatic lobe. One required reintubation in the recovery room and remained
      intubated overnight. The other was extubated but required observation in the
      intensive care unit for a low respiratory rate. Twelve patients (16.2%) had
      complaints of nausea, and two reported nausea with vomiting during their hospital
      stay. There were four patients who developed complications related to positioning
      during the surgery: Two patients complained of numbness and tingling in the hands
      which resolved within two days, one patient reported a blister on the hand, and
      one patient complained of right elbow pain that resolved quickly. Postoperative
      hospitalization averaged 7.4 +/- 1.5 days. There was no patient mortality.
      DISCUSSION: Living liver donation can be performed with low morbidity. However,
      postoperative respiratory depression is a concern and is perhaps due to altered
      metabolism of administered narcotics and anesthetic agents.

PMID- 21897511
TI  - Pneumothorax during laparoscopic repair of giant paraesophageal hernia.
AB  - Giant paraesophageal hernia is an uncommon morbid disorder which may present a
      risk of catastrophic complications and should be repaired electively as soon as
      possible. Laparoscopic fundoplication is the mainstay of surgical management of
      this disorder due to several advantages such as lower post-operative morbidity
      and pain. We report a case of a 70-year-old patient with a giant paraesophageal
      hernia, who developed subcutaneous emphysema with pneumothorax during
      laparoscopic fundoplication. Early diagnosis was possible by close clinical
      evaluation and simultaneous monitoring of end-tidal carbon dioxide levels and
      airway pressures. Although positive end-expiratory pressure application is an
      effective way of managing pneumothorax secondary to the passage of gas into the
      interpleural space, insertion of an intercostal drain may be used in an emergent
      situation.

PMID- 21897510
TI  - Comparison of dexmedetomidine and three different doses of midazolam in
      preoperative sedation.
AB  - BACKGROUND: This study was conducted to compare the efficacy and effects of
      dexmedetomidine and midazolam in preoperative sedation. MATERIALS AND METHODS: A
      total of 125 patients in American Society of Anaesthesiologists (ASA) I-II were
      divided into three groups: Group I (n = 40) for controls, Group II (n = 40) for
      Dexmedetomidine (1 MUg/kg), and group III was the midazolam group (n = 45). Group
      III was further divided into three subgroups according to the doses of midazolam:
      Group IIIA (n = 15) received 0.02 mg/kg, group IIIB (n = 15) received 0.04 mg/kg,
      and group IIIC (n = 15) received 0.06 mg/kg of midazolam. Drugs were infused over
      a 10-minute period with appropriate monitoring. Ramsay and visual analog scores,
      for sedation and anxiety, respectively, and mean arterial pressure, heart rate,
      and SpO(2) measurement, including respiratory rates were recorded, every 5
      minutes for 30 minutes following infusion. RESULTS: There was marked sedation and
      a decrease in anxiety in groups II and IIIC (P < 0.01). Mean arterial pressure
      (MAP) and heart rate (HR) decreased significantly in group II (P < 0.01 and P <
      0.05, respectively), but there was no associated hypotension (MAP <60 mm Hg) or
      bradycardia (HR <50 bpm) (P < 0.05). Respiratory rates and SpO(2) values
      decreased in groups II, IIIA, IIIB, and IIIC. The differences in respiratory
      rates were not significant (P > 0.05); however, decrease in SpO(2) was
      significant in group IIIC (P < 0.01). CONCLUSIONS: Dexmedetomidine was as
      effective as higher doses of midazolam in sedation. The hemodynamic and
      respiratory effects were minimal. Although dexmedetomidine caused significant
      decrease in the blood pressure and heart rate, it probably just normalized
      increased levels caused by preoperative stress.

PMID- 21897512
TI  - Epidural anesthesia for repeat cesarean delivery in a parturient with Klippel
      Feil syndrome.
AB  - A patient with Klippel-Feil syndrome, morbid obesity, and scoliosis required
      cesarean delivery. Her previous cesarean deliveries were performed under general
      anesthesia. She desired a regional technique. Following aspiration prophylaxis
      and placement of standard monitors, ultrasound was used to identify midline and
      L(2-3) interspace. Unintentional dural puncture occurred at 10 cm, with an
      inability to advance the catheter. On second attempt, an epidural catheter was
      placed easily. After negative test dose, 18 ml of 2% lidocaine with epinephrine
      was administered to the patient. A T4 level was achieved. The patient tolerated
      surgery well. Complete block resolution occurred at 4 hours with no neurologic
      sequelae.

PMID- 21897514
TI  - Anesthetic management of a patient with Kimura's disease for superficial
      parotidectomy.
AB  - Kimura's disease is a rare form of chronic eosinophilic inflammatory disease with
      vascular proliferation involving salivary gland, skin, lymph node, and kidney.
      Important anesthetic concerns include increased surgical bleeding due to its
      vascular nature, airway involvement by the mass leading to a possible difficult
      airway, allergic symptoms associated with high eosinophil count and elevated IgE
      level and nephrotic syndrome due to involvement of kidney by the inflammatory
      process. There is paucity of information in the literature on the anesthetic
      management of Kimura's disease. We describe the anesthesia technique and review
      the literature of such a case posted for superficial parotidectomy.

PMID- 21897513
TI  - Rocuronium and sugammadex: An alternative to succinylcholine for electro
      convulsive therapy in patients with suspected neuroleptic malignant syndrome.
AB  - We report a case of presumptive neuroleptic malignant syndrome requiring muscle
      relaxation for electro-convulsive therapy. short acting muscle relaxation without
      the use of succinylcholine was achieved using rocvronivm reversed with the novel
      reversal agent sugammadex. We suggest that this combination is a safe and
      effective alternative to succinylcholine in such cases.

PMID- 21897515
TI  - Prolonged vertigo and ataxia after mandibular nerve block for treatment of
      trigeminal neuralgia.
AB  - Common complications of neurolytic mandibular nerve block are hypoesthesia,
      dysesthesia, and chemical neuritis. We report a rare complication, prolonged
      severe vertigo and ataxia, after neurolytic mandibular blockade in a patient
      suffering from trigeminal neuralgia. Coronoid approach was used for right sided
      mandibular block. After successful test injection with local anesthetic, absolute
      alcohol was given for neurolytic block. Immediately after alcohol injection,
      patient developed nausea and vomiting along with severe vertigo, ataxia and
      hypertension. Neurological evaluation was normal except for the presence of
      vertigo and ataxia. Computerised tomography scan brain was also normal. Patient
      was admitted for observation and symptomatic treatment was given. Vertigo and
      ataxia gradually improved over 24 hours.

PMID- 21897516
TI  - Airway management of an unusual case of recurrent rhinoscleroma.
AB  - Rhinoscleroma is a rare entity encountered in anesthesia practice. We discuss the
      management of a patient after its recurrence, involving the upper respiratory
      tract i.e. nasopharynx and oropharynx, which compromised the airway. The pateint
      was referred for anesthesia on three different occasions with different
      presentations owing to the recurrence of symptoms.The presence of an
      oropharyngeal membrane with a small opening made airway management a challenge.
      The patient was successfully managed on all three occasions. Imaging facilitated
      assessment and subsequent airway management.

PMID- 21897517
TI  - Tetany: A diagnostic dilemma.
AB  - Tetany is a disorder of increased neuronal excitability usually associated with
      hypocalcemia. We report a patient with typical tetanic cramps and carpopedal
      spasm in the postoperative period, despite normal serum concentrations of
      calcium, which responded to intravenous infusion of calcium.

PMID- 21897518
TI  - Failed nasal intubation after successful flexible bronchoscopy: Guide wire to the
      rescue.
AB  - Flexible fiberoptic bronchoscope-guided awake intubation is the most trusted
      technique for managing an anticipated difficult airway. Even after successfully
      negotiating the bronchoscope into the trachea, the possibility remains that the
      preloaded tracheal tube might prove to be inappropriately large, and may not
      negotiate the nasal structures. In such a situation, the most obvious solution is
      to take out the bronchoscope, replace the tracheal tube with a smaller one, and
      repeat the procedure. Unfortunately, sometimes the second attempt is not as easy
      as the first, as minor trauma during the earlier attempt causes tissue edema and
      bleeding, which makes the subsequent bronchoscopic view hazy and difficult. We
      present the anesthetic management of five cases with temporomandibular joint
      ankylosis where, after successful, though slightly traumatic, bronchoscope
      insertion into the trachea, the tube could not be threaded in. We avoided a
      repeat bronchoscopy by making an innovative change in the plan.

PMID- 21897519
TI  - Abnormal oculocardiac reflex in two patients with Marcus Gunn syndrome.
AB  - Marcus Gunn phenomenon is seen in 4 to 6% of congenital ptosis patients. We
      report two cases of abnormal oculocardiac reflex during ptosis correction
      surgery. Marcus Gunn syndrome is an autosomal dominant condition with incomplete
      penetrance. It is believed to be a neural misdirection syndrome in which fibres
      of the motor division of the trigeminal nerve are congenitally misdirected into
      the superior pterygoid and the levator muscles. Anesthetic considerations include
      taking a detailed history about any previous anaesthetic exposure and any
      reaction to it as this syndrome has a high probability of being associated with
      malignant hyperthermia. It is also postulated that an atypical oculocardiac
      reflex might be initiated in these patients as seen in our patients, so
      precautions must be taken for its prevention and early detection.

PMID- 21897520
TI  - Anesthetic considerations in a patient of autosomal dominant polycystic kidney
      disease on hemodialysis for emergency cesarean section.
AB  - Renal disease, either preexisting or occurring during gestation may impair
      maternal and fetal health. A 35-year-old primigravida with autosomal dominant
      polycystic kidney disease on hemodialysis was scheduled for emergency cesarean
      section. She was managed successfully with low-dose intrathecal bupivacaine and
      fentanyl. In the case of pregnancy in such a patient, early involvement of the
      nephrologists along with the obstetrician can improve maternal and fetal outcome.

PMID- 21897521
TI  - Pneumothorax complicating pulmonary embolism after combined spinal epidural
      anesthesia in a chronic smoker with open femur fracture.
AB  - Pulmonary embolism during or after regional anaesthesia is although very rare, it
      has been reported in cases undergoing lower limb orthopedic procedures. We
      presenting a 48 years old male, a known smoker since 25 years, with history of
      road traffic accident and open fracture right femur for external fixation.
      Combined spinal epidural anaesthesia was given. After 35 minutes patient
      complained dyspnea and chest pain. SpO2 decreased to 82% from 100%. Continuous
      positive airway pressure with 100% oxygen was given. SpO2 increased from 82% to
      96%. Suddenly he had bouts of cough and SpO2 became 79-80% with unstable
      haemodynamics. On chest auscultation there was decreased breath sounds on right
      side with limited expansion. Trachea was intubated after inducing anaesthesia
      with fentanyl 70 MUg and thiopental 300 mg. Chest radiograph showed right sided
      pneumothorax. Intercostal drain with a water seal was put. After 5 minutes HR was
      80/min, BP was 110/69 mmHg and SpO2 was 97%. Pulmonary thromboembolism secondary
      to deep vein thrombosis was suspected and was confirmed by D-dimer Elisa and
      color Doppler of lower limbs. Patient was shifted to intensive care unit after
      completion of surgery. Anticoagulant therapy was started. He was weaned from the
      ventilator on 3rd day and trachea was extubated. Chest drain was removed after 9
      days and he was discharged from hospital on 15th post operative day.

PMID- 21897522
TI  - Unrecognized blunt tracheal trauma with massive pneumomediastinum and tension
      pneumothorax.
AB  - Blunt neck trauma with an associated laryngotracheal injury is rare. We report a
      patient with blunt neck trauma who came to the emergency room and was sent to
      ward without realizing the seriousness of the situation. He presented later with
      respiratory distress and an anesthesiologist was called in for emergency airway
      management. Airway management in such a situation is described in this report.

PMID- 21897523
TI  - Tension pneumoventricle after excision of third ventricular tumor in sitting
      position.
AB  - Occurrence of tension pneumoventricle (symptomatic intraventricular air) can
      result in rapid clinical deterioration in an otherwise stable patient. It is a
      rare clinical entity, mentioned in relation to cerebrospinal fluid (CSF)
      diversion procedures, during the late postoperative period. We present a patient
      with posterior third ventricular tumor who underwent excision by midline
      suboccipital craniotomy in sitting position. Neurological status of the patient
      deteriorated rapidly in the immediate postoperative period owing to development
      of tension pneumoventricle. The condition improved after twist-drill burr-hole
      evacuation of air under water-seal. Pre-existing gross hydrocephalus, exploration
      of third ventricle in sitting position, and residual tumor in third ventricle
      were possibly the factors responsible for this complication.

PMID- 21897524
TI  - Anesthetic management for laparoscopy surgery in a patient with residual
      coarctation of aorta and mild aortic stenosis.
AB  - Perioperative management of patients with congenital heart disease is a challenge
      for the anesthesiologist. We present successful anesthetic management for
      diagnostic laparoscopy and cystectomy for tubo-ovarian mass in a case of residual
      coarctation of the aorta along with bicuspid aortic valve and mild aortic
      stenosis.

PMID- 21897525
TI  - Unique airway finding in a case of Pfeiffer syndrome and its management.

PMID- 21897526
TI  - Leaks in the vaporizer unit: Still a possibility.

PMID- 21897527
TI  - Huge vulval elephantiasis: Anesthetic management for caesarean delivery.

PMID- 21897528
TI  - Can the use of sevoflurane with rocuronium reconcile the debate on
      succinylcholine versus rocuronium for rapid sequence intubation?

PMID- 21897529
TI  - Gangrene of hand due to faulty intravenous cannulation: Be cautious with
      hyperosmotic agents.

PMID- 21897530
TI  - Muscle twitching and hiccups with propofol.

PMID- 21897531
TI  - Arrhythmias in prone position.

PMID- 21897532
TI  - Anesthetic management of cystic hygroma of tongue in a child.

PMID- 21897533
TI  - Authors' reply.

PMID- 21897534
TI  - Failed insertion of endotracheal tube through classic laryngeal mask airway.

PMID- 21897535
TI  - Monitoring of neuromuscular blockade by pulse oximetry tracing: A simple
      modification of mechanomyographic and acceleromyographic principles.

PMID- 21897536
TI  - Nonconventional way of securing endotracheal tube in bearded individuals.

PMID- 21897537
TI  - Acute epiglottic abscess in adults: Still a challenge!

PMID- 21897539
TI  - Anesthetic considerations in periventricular leucomalacia.

PMID- 21897538
TI  - Ultrasound-guided regional blockade - Is it always safe?

PMID- 21897540
TI  - Fine needle aspiration cytology in lesions of oral and maxillofacial region:
      Diagnostic pitfalls.
AB  - BACKGROUND: Fine needle aspiration cytology (FNAC) of oral and maxillofacial
      region has not been widely utilized for diagnosis due to diversity of lesion
      types, heterogeneity of cell populations and difficulties in reaching and
      aspirating these lesions. AIM: Our aim was to demonstrate the effectiveness of
      this cheap and simple procedure for the diagnosis of tumor and tumor like lesions
      of oral and maxillofacial region. In addition, we sought to highlight probable
      causes of errors in the cases showing lack of correlation between cytological and
      histological diagnoses. MATERIALS AND METHODS: The study was conducted on 50
      patients of all age groups with various palpable lesions in the oromaxillofacial
      region. A comparison between cytological and histological diagnosis was done
      wherever biopsy material was available. RESULTS: The rate of unsatisfactory FNA
      was 4%. There were six false negative cases but no false positive case. The
      sensitivity of our study ranged from 77.7 to 75% including and excluding the
      suspicious cases, respectively. Specificity and positive predictive value was
      100%. CONCLUSION: FNAC is a minimally invasive, highly accurate and cost
      effective procedure for the assessment of patients with oromaxillofacial lesions.
      When applied in a proper manner, FNAC can help avoid a surgical biopsy in many
      cases.

PMID- 21897541
TI  - Morphology to morphometry in cytological evaluation of thyroid lesions.
AB  - AIM: To evaluate the cytomorphometric features in fine needle aspiration cytology
      (FNAC) of thyroid lesions. MATERIALS AND METHODS: FNAC of 36 thyroid cases was
      reviewed. The study included 10 cases each of follicular lesion, adenomatous
      goiter, papillary carcinoma, 4 cases of medullary carcinoma and 2 cases of
      anaplastic carcinoma. Their ages ranged from 28 to 50 years, and there were nine
      females and one male. Morphometric analysis was done on aspiration smears from 36
      thyroid lesions. Hematoxylin and Eosin stained smears were examined using image
      analyzer Proplus V software. Morphological parameters measured included mean
      nuclear diameter, mean nuclear perimeter, mean nuclear area, circular rate,
      largest to smallest dimension ratio (LS ratio) and coefficient of variation of
      nuclear area (NACV). STATISTICAL ANALYSIS: Statistical evaluation was carried out
      using the analysis of variance (ANOVA) test for the five variables, both within
      the group and in between the groups. The result was considered significant when P
      < 0.05. RESULTS: The follicular carcinomas had higher LS ratio than patients with
      adenomatous goiters. Mean nuclear diameter and the mean nuclear perimeter were
      higher in anaplastic carcinomas when compared to other subtypes and were the
      least for follicular neoplasms. CONCLUSION: When correctly applied, quantitative
      estimation of cytological nuclear features can play an important role in
      preoperative assessment and can complement morphological features in thyroid
      lesions.

PMID- 21897542
TI  - Fine needle aspiration cytology of epididymal nodules.
AB  - BACKGROUND: The incidence of non neoplastic lesions are much more common in
      epididymis. Clinically, epididymal nodules are easily accessible to fine needle
      aspiration cytology (FNAC) procedure. There are very few literature reports
      documenting the role of cytology in evaluation of epididymal nodules. Thus, we
      studied patients presenting with palpable epididymis nodules in the out patient
      department (OPD) from a tertiary care general hospital. AIM: This study is aimed
      to put forth the diagnostic utility of FNAC in palpable lesions of epididymis.
      MATERIALS AND METHODS: A total of 40 palpable epididymal nodules were aspirated
      as a routine OPD procedure as part of this study. Smears were fixed in isopropyl
      alcohol and air dried. In all the cases, wet fixed papanicoloau stained and air
      dried giemsa stained smears were studied. Zeihl Neelsen stain was performed in
      cases which yielded caseous aspirate. RESULTS: Except for two cases of
      adenomatoid tumor of epididymis all other lesions were nonneoplastic and included
      14 cases (35%) of tuberculous granulomatous inflammation, 10 (25%) cystic nodules
      (9 spermatoceles and 1 encysted hydrocele), 5 (12.5%) of nonspecific
      inflammations, 3 (7.5%) filarial infection, 3 (7.5%) sperm granulomas and 3
      (7.5%) adenomatous hyperplasia of rete testes. Except for the two tumors, one
      adenomatous hyperplasia and one tuberculous lesion, no other lesion was excised.
      Follow up and response to therapy was available in 78% patients and resolution
      indicated appropriateness of the diagnosis CONCLUSIONS: Thus, as most of the
      lesions in epididymis are non neoplastic responding to medical line of treatment
      and FNAC served to aid diagnosis of non specific inflammation and avoid surgical
      excision in most cases.

PMID- 21897544
TI  - The clinical effectiveness of fine needle aspiration biopsy in patients with
      palpable breast lesions seen at the University College Hospital, Ibadan, Nigeria:
      A 10-year retrospective study.
AB  - BACKGROUND: Although open surgical biopsy is the 'gold standard' for diagnosis of
      palpable breast lesions, in recent years two types of minimally invasive breast
      biopsy techniques, core needle biopsy and fine needle aspiration biopsy (FNAB),
      have become established for the diagnostic evaluation of palpable breast lesions.
      AIMS: This study was undertaken to evaluate the clinical effectiveness of FNAB as
      a first line diagnostic procedure in the management of patients with breast lumps
      in University College Hospital (UCH), Ibadan, using the suggested thresholds for
      cytology performance as recommended by the United Kingdom National Health
      Services Breast Screening Programme (NHSBSP). SETTINGS AND DESIGN: A 10-year
      retrospective cohort study carried out in the Pathology Department of UCH.
      MATERIALS AND METHODS: All FNAB and histologically diagnosed cases of breast
      lesions in the pathology department between January 1996 and December 2005 were
      reviewed. The cytological diagnoses were then categorized into one of five
      diagnostic categories in accordance with the recommendations of the NHSBSP.
      RESULTS: The positive predictive value for malignancy was 99.3% with a complete
      sensitivity of 97.7% and specificity (full) of 94.2%. CONCLUSIONS: The high
      quality assurance measures obtained in this study affirms FNAB as a clinically
      effective diagnostic procedure for breast lesions.

PMID- 21897543
TI  - Fine needle aspiration cytology of supraclavicular lymph nodes: Our experience
      over a three-year period.
AB  - AIMS: This study was taken up with the aim to investigate the pattern of
      supraclavicular lymphadenopathy among patients presenting to our tertiary care
      institution, evaluate the diagnostic efficacy of fine needle aspiration cytology
      (FNAC), and analyze the diagnostic pitfalls. MATERIALS AND METHODS: A total of
      215 patients were subjected to FNAC of supraclavicular lymph nodes over a three
      year period (August 2006 to July 2009). Since in 18 patients as either the
      aspirate was inadequate or the opinion was equivocal, we analyzed the remaining
      197 cases. RESULTS: Malignant pathology accounted for 79.7% (157/197) of the
      cases. These were mostly cases of metastatic squamous cell carcinoma (79/197,
      40.1%), adenocarcinoma (47/197, 23.9%), small cell carcinoma (12/197, 6.1%) and
      lymphoma (10/197, 5%). There were 28 (14.2%) cases of tuberculosis. Out of these
      197 patients, 92 patients were biopsied. The opinion based on FNAC was erroneous
      in 6 cases but corroborated with the final histopathology findings in the
      remaining 86 cases. CONCLUSION: FNAC is an excellent first line of investigation;
      and when used with a proper combination of experience and diligence, it can
      greatly reduce the number of errors.

PMID- 21897545
TI  - Radio-pathological diagnosis of hepatobiliary ascariasis: A rare entity.
AB  - Ascariasis is the commonest helminthic infection in humans, caused by the
      nematode Ascaris lumbricoides. The adult worms usually reside in the small
      intestine. Rarely, they migrate into the bile duct and pancreatic ducts, but
      involvement of the gall bladder and/or liver parenchyma is extremely rare. Here,
      we describe a case of a 32-year-old woman who presented with fever, anorexia,
      right upper quadrant pain and mild hepatomegaly. Ultrasonography revealed a liver
      abscess and a concurrent moving adult worm in the gall bladder. Fine-needle
      aspiration cytology (FNAC) from the liver abscess showed presence of fertilized
      eggs of Ascaris lumbricoides. A diagnosis of gall bladder and hepatic ascariasis
      was made. The patient responded well to conservative management. Ascaris-induced
      liver abscess with concurrent living adult worm in gall bladder has rarely been
      reported. Ultrasonography and FNAC are important diagnostic modalities for
      detection of such lesions. Conservative management appears to be the treatment of
      choice for hepatobiliary ascariasis.

PMID- 21897546
TI  - The cytology of intracranial clear cell meningioma with an unusual scalp
      presentation.
AB  - Intracranial meningiomas are not often aspirated unless they erode the skull and
      present as swelling in the head and neck region. We describe the cytologic
      findings of fine needle aspiration cytology in a clear cell variant of
      intracranial meningioma presenting with swelling in the left parietal region of
      the scalp in a 45-year-old woman. The diagnosis was confirmed by histopathology.
      Clear cell meningioma is characterized by patternless sheets of clear polygonal
      cells. Clear cell meningioma is a rare distinctive cytological subtype of
      meningioma with high recurrence rate and increased mortality, which necessitate
      frequent follow-up after surgical excision. The recognition of clear cell
      meningiomas is important here and should be distinguished from other clear cell
      lesions of the scalp. If clear cell epithelial neoplasm is encountered on fine
      needle aspiration, it is reasonably possible to provide at least a differential
      diagnosis of meningioma based upon the focal whorls, sparce vascularity on low
      magnification, along with the presence of pseudoinclusion and inconspicuous
      nucleoli at high magnification.

PMID- 21897547
TI  - Fine needle aspiration cytology of metastatic alveolar rhabdomyosarcoma.
AB  - Rhabdomyosarcoma (RMS) is an aggressive malignant soft tissue tumor that arises
      from primitive striated muscle cells called rhabdomyoblasts. RMS is a rare tumor
      in adults, and involvement of the sinonasal area is extremely rare, comprising
      only 1.5% of all reported head and neck RMSs. Alveolar RMS, mainly seen in
      adults, has the worst prognosis. Incidence of lymph node metastases is more
      common in this type compared with the other forms. Fine needle aspiration
      cytology (FNAC) has been used extensively in the diagnosis of metastatic
      malignancies. However, metastatic soft tissue sarcomas are often overlooked,
      primarily due to the low frequency with which they occur. Here, we report a rare
      case of metastatic alveolar RMS in the cervical lymph nodes of an 18-year-old
      girl that was detected by FNAC. After 6 months, the patient came with a huge mass
      involving the nasal vestibule and the upper lip. Histology of both the main mass
      and the lymph nodes revealed alveolar RMS.

PMID- 21897548
TI  - The mystic thyroid nodule: A cytologist's confront.
AB  - Metastatic thyroid carcinoma is clinically silent and found only at autopsy in
      most instances. Renal cell carcinoma (RCC) is the most common and constitutes 56%
      of all secondary malignancies. However, preoperative distinction between primary
      and secondary thyroid neoplasms is often challenging. Fine needle aspiration is
      helpful in establishing a correct preoperative diagnosis. A local surgical
      resection is curative if prompt preoperative diagnosis is established. We hereby
      report a case of isolated metastatic RCC to the thyroid in a 65-year-old woman,
      diagnosed by fine needle aspiration cytology and later confirmed with
      histopathological examination.

PMID- 21897549
TI  - Fine needle aspiration cytology of a case of micropapillary variant of urothelial
      carcinoma of bladder.
AB  - Neoplastic urothelium has the capacity to demonstrate enormous plasticity. A
      variety of unusual morphological variants of urothelial carcinoma have been
      described. Micropapillary variant of urothelial carcinoma is a rare and recently
      described bladder tumor, associated with poor prognosis. We present the
      cytological features of micropapillary urothelial carcinoma in a 65-year-old man
      with bladder mass. The cytological features include tightly cohesive clusters of
      micropapillary component admixed with urothelial carcinoma. Histopathological
      sections showed small nests of tumor cells residing within the lacunae.
      Establishing a diagnosis of micropapillary urothelial carcinoma indicates a high
      grade and high-stage tumor with poor outcome, requiring an aggressive therapy. It
      is thus important for the cytopathologist to recognise micropapillary variant of
      urothelial carcinoma, for early and better management of patients with bladder
      tumor.

PMID- 21897550
TI  - Extranodal manifestation of Rosai-Dorfman disease with bilateral ocular
      involvement.
AB  - Rosai-Dorfman disease, that is, sinus histiocytosis with massive lymphadenopathy
      is a benign systemic proliferative disorder of histiocytes. The typical clinical
      presentation of the disease includes bilateral painless massive lymphadenopathy,
      fever and polyclonal hypergammaglobulinemia. Extranodal involvement is present in
      only a few cases and skin lesions are the most common form of extranodal disease.
      However, purely cutaneous Rosai-Dorfman disease is uncommon. In this study, we
      describe a 10-year-old child presenting with bilateral ocular involvement.

PMID- 21897551
TI  - Cytological diagnosis of typical carcinoid on bronchoscopic brush smears in an
      HIV-positive patient.
AB  - We report a case of typical carcinoid of the lung in a 60-year-old human
      immunodeficiency virus (HIV)-positive man diagnosed on brush cytology smears.
      Bronchial carcinoids are rare tumors, accounting for 1% to 2% of all lung tumors.
      Although the exact incidence in HIV-infected individuals is not known, the
      paucity of their documentation in the literature indicates that they may be
      equally rare. Cytological diagnosis on brush smears is rarely documented as the
      tumor is covered with mucosa and cellular yield is often not good. In this case,
      bronchial brushings showed distinctive cytological features of typical carcinoid.
      The awareness of its characteristic cytological features and differential
      diagnosis is required for an accurate diagnosis. Clinical awareness that non
      acquired immunodeficiency syndrome (AIDS)-defining cancers can also occur in HIV
      infected individuals in the context of the prolonged survival in the
      antiretroviral era is equally important. This case emphasizes the clinical
      importance of a broad differential diagnosis for lung lesions in HIV-positive
      patients.

PMID- 21897552
TI  - Coexistence of leukemic infiltration and extramedullary hematopoeisis in a lymph
      node: A cytological diagnosis.
AB  - Extramedullary hematopoeisis (EMH) occurs when function of the bone marrow is
      insufficient or destroyed. We report a case of lymph nodal mass in a young
      patient, diagnosed on fine needle aspiration cytology (FNAC) as infiltration by
      leukemia along with features of EMH. FNA smears from axillary lymph node revealed
      lymphoblasts with hand mirror cell and teat cell morphology. Also seen were
      occasional megakaryocytes and metamyelocytes.

PMID- 21897553
TI  - Cytodiagnosis and pitfalls of genital tuberculosis: A report of two cases.
AB  - Genital tuberculosis is fairly common in Indian women due to high prevalence of
      pulmonary tuberculosis in the general population. Histopathological diagnosis is
      invaluable but often, diagnosis can be made with reasonable accuracy by
      Papanicolaou (Pap) smear test if the index of suspicion is kept high. Also,
      genital tuberculosis is considered to be more common in patients less than 40
      years of age and rare after menopause. We describe two cases of cervical
      tuberculosis in patients over 40 years of age, including a postmenopausal case,
      diagnosed by smear tests and later confirmed by histopathology and bacteriology.
      The differential diagnoses as well as problems encountered in the diagnosis of a
      tuberculous lesion in Pap smears are also discussed.

PMID- 21897554
TI  - Primary tuberculous parotitis.

PMID- 21897555
TI  - Cryptococcus in pleural fluid cytology in a patient with hepatitis B virus
      associated chronic liver disease.

PMID- 21897556
TI  - Unflattened photon beams from the standard flattening filter free accelerators
      for radiotherapy: Advantages, limitations and challenges.

PMID- 21897557
TI  - A quality index for equivalent uniform dose.
AB  - Equivalent uniform dose (EUD) is the absorbed dose that, when homogeneously given
      to a tumor, yields the same mean surviving clonogen number as the given non
      homogeneous irradiation. EUD is used as an evaluation tool under the assumption
      that two plans with the same value of EUD are equivalent, and their biological
      effect on the tumor (clonogen survival) would be the same as the one of a
      homogeneous irradiation of absorbed dose EUD. In this work, this assumption has
      been studied, and a figure of merit of its applicability has been obtained.
      Distributions of surviving clonogen number for homogeneous and non-homogeneous
      irradiations are found to be different even if their mean values are the same,
      the figure of merit being greater when there is a wider difference, and the
      equivalence assumption being less valid. Therefore, EUD can be closer to a
      uniform dose for some cases than for other ones (high alpha values, extreme
      heterogeneity), and the accuracy of the radiobiological indices obtained for
      evaluation, could be affected. Results show that the equivalence is very
      sensitive to the choice of radiobiological parameters, and this conclusion has
      been derived from mathematical properties of EUD.

PMID- 21897558
TI  - Variation of beam characteristics between three different wedges from a dual
      energy accelerator.
AB  - The use of megavoltage X-ray sources of radiation, with their skin-sparing
      qualities in radiation therapy, has been proved useful in relieving patient
      discomfort and allowing higher tumor doses to be given with fewer restrictions
      due to radiation effects in the skin. The purpose of this study was to compare
      the dosimetric characteristics of a physical and enhanced dynamic wedge from a
      dual-energy (6 and 18 MV) linear accelerator such as surfaces doses with
      different source to surface distances (SSD), half value layer (HVL) in water and
      peripheral doses for both available energies. At short SSD such as 85 cm, higher
      surface doses are produced by the lower wedges by the short wedge-to-skin
      distance. For physical wedged field, at heel edge side HVL value was high (17 cm)
      compared with the measured that of EDW (15.1 cm). It was noticed that, the HVL
      variation across the beam was significantly higher for 6 MV X-rays than for 18 MV
      X-rays. The lower wedge has the maximum variation of peripheral dose compared to
      other wedges. The three wedge systems discussed in this work possess vastly
      different dosimetric characteristics. These differences will have a direct impact
      on the choice of the wedge system to be used for a particular treatment. Complete
      knowledge of the dosimetric characterisitics, including the surface and
      peripheral doses, is crucial in proper choice of particular wedge systems in
      clinical use.

PMID- 21897559
TI  - Performance evaluation of three computed radiography systems using methods
      recommended in American Association of Physicists in Medicine Report 93.
AB  - The performances of three clinical computed radiography (CR) systems, (Agfa CR 75
      (with CRMD 4.0 image plates), Kodak CR 850 (with Kodak GP plates) and Kodak CR
      850A (with Kodak GP plates)) were evaluated using six tests recommended in
      American Association of Physicists in Medicine Report 93. The results indicated
      variable performances with majority being within acceptable limits. The
      variations were mainly attributed to differences in detector formulations, plate
      readers' characteristics, and aging effects. The differences of the mean low
      contrast scores between the imaging systems for three observers were
      statistically significant for Agfa and Kodak CR 850A (P=0.009) and for Kodak CR
      systems (P=0.006) probably because of the differences in ages. However, the
      differences were not statistically significant between Agfa and Kodak CR 850
      (P=0.284) suggesting similar perceived image quality. The study demonstrates the
      need to implement quality control program regularly.

PMID- 21897560
TI  - Development of image-processing software for automatic segmentation of brain
      tumors in MR images.
AB  - Most of the commercially available software for brain tumor segmentation have
      limited functionality and frequently lack the careful validation that is required
      for clinical studies. We have developed an image-analysis software package called
      'Prometheus,' which performs neural system-based segmentation operations on MR
      images using pre-trained information. The software also has the capability to
      improve its segmentation performance by using the training module of the neural
      system. The aim of this article is to present the design and modules of this
      software. The segmentation module of Prometheus can be used primarily for image
      analysis in MR images. Prometheus was validated against manual segmentation by a
      radiologist and its mean sensitivity and specificity was found to be 85.71+/
      4.89% and 93.2+/-2.87%, respectively. Similarly, the mean segmentation accuracy
      and mean correspondence ratio was found to be 92.35+/-3.37% and 0.78+/-0.046,
      respectively.

PMID- 21897561
TI  - Comparison of no-prior and soft-prior regularization in biomedical microwave
      imaging.
AB  - Microwave imaging for medical applications is attractive because the range of
      dielectric properties of different soft tissues can be substantial. Breast cancer
      detection and monitoring of treatment response are areas where this technology
      could be important because of the contrast between normal and malignant tissue.
      Unfortunately, the technique is unable to achieve the high spatial resolution at
      depth in tissue which is available from other conventional modalities such as x
      ray computed tomography (CT) or magnetic resonance imaging (MRI). We have
      incorporated a soft-prior regularization strategy within our microwave
      reconstruction algorithm and compared it with the images obtained with
      traditional no-prior (Levenberg-Marquardt) regularization. Initial simulation and
      phantom results show a significant improvement of the recovered electrical
      properties. Specifically, errors in the microwave property estimates were
      improved by as much as 95%. The effects of a false-inclusion region were also
      evaluated and the results show that a small residual property bias of 6% in
      permittivity and 15% in conductivity can occur that does not otherwise degrade
      the property recovery accuracy of inclusions that actually exist. The work sets
      the stage for integrating microwave imaging with MR for improved resolution and
      functional imaging of the breast in the future.

PMID- 21897562
TI  - Relative dosimetrical verification in high dose rate brachytherapy using two
      dimensional detector array IMatriXX.
AB  - For high dose rate (HDR) brachytherapy, independent treatment verification is
      needed to ensure that the treatment is performed as per prescription. This study
      demonstrates dosimetric quality assurance of the HDR brachytherapy using a
      commercially available two-dimensional ion chamber array called IMatriXX, which
      has a detector separation of 0.7619 cm. The reference isodose length, step size,
      and source dwell positional accuracy were verified. A total of 24 dwell
      positions, which were verified for positional accuracy gave a total error
      (systematic and random) of -0.45 mm, with a standard deviation of 1.01 mm and
      maximum error of 1.8 mm. Using a step size of 5 mm, reference isodose length (the
      length of 100% isodose line) was verified for single and multiple catheters of
      same and different source loadings. An error <=1 mm was measured in 57% of tests
      analyzed. Step size verification for 2, 3, 4, and 5 cm was performed and 70% of
      the step size errors were below 1 mm, with maximum of 1.2 mm. The step size <=1
      cm could not be verified by the IMatriXX as it could not resolve the peaks in
      dose profile.

PMID- 21897563
TI  - Dosimetric analysis of beam-matching procedure of two similar linear
      accelerators.
AB  - Linear accelerators from the same vendor in a radiation therapy center are
      usually beam-matched following Vendor's acceptance criteria. This protocol is
      limited to check the difference at particular points on the ionization curve for
      depth dose or beam profiles. This article describes different tests done after
      commissioning to evaluate the level of agreement between matched beams of two
      ONCOR Impression plus linear accelerators from Siemens. Total scatter factors,
      collimator scatter factors, wedge transmission factors were measured in water for
      6-MV photon. All these factors for ONCOR2 were within +/-1% of those values for
      ONCOR1. Along with these point dose measurements we have essentially used gamma
      index to compare the planar dose distribution from two beam-matched accelerators.
      For this study a set of ready packed EDR2 films was exposed on both accelerators.
      The set consisted of films for percentage depth dose, beam profiles, a pyramid
      shape, multileaf collimator's positional and dose delivery accuracy, and a film
      to compare head scatter at tray level. To include treatment planning system
      calculations, a film kept in axial plane was exposed to 3DCRT and IMRT plans with
      actual gantry angles and monitor units. These films were analyzed for gamma in
      OmniPro IMRT software using different combinations of Deltadose and -
      Deltadistances. All these films have shown good agreement for - Deltadistance of
      3 mm and Deltadose of 3 %.

PMID- 21897564
TI  - Need of patient-specific quality assurance and pre-treatment verification program
      for special plans in radiotherapy.

PMID- 21897565
TI  - Bladder exstrophy: An overview of the surgical management.
AB  - BACKGROUND: The surgical management of urinary bladder exstrophy is challenging.
      This paper describes the personal experience in a tertiary care hospital over a
      period exceeding a quarter of a century. METHODS: During the period 1984-2010,
      248 patients of the epispadias-exstrophy complex have been treated. The cases of
      classical bladder exstrophy (n = 210) form the basis of this paper. The
      stages/procedures used in the surgical reconstruction of bladder exstrophy
      included bladder closure with anterior abdominal wall reconstruction, bladder
      neck repair, ureteric reimplantation, epispadias repair and augmentation
      colocystoplasty in various combinations. Some of these patients had their initial
      operations done prior to 1984 or in other hospitals. Evaluation methods included,
      amongst others, clinical evaluation and urodynamic assessment. Eight patients
      opted out of treatment; 15 patients underwent permanent urinary diversion by
      either ureterosigmoidostomy or colon conduit. The remaining 187 patients were
      treated with bladder reconstruction, and of these, 132 patients have had at least
      one attempt at bladder neck reconstruction with 56 of these patients having
      undergone an augmentation colocystoplasty. RESULTS: A total of 105 patients had
      socially acceptable continence: 57 from the bladder neck reconstruction group and
      48 from the bladder augmentation group. Further attempts at continence surgery
      have been offered to the inadequately continent patients. CONCLUSIONS: Surgical
      management of bladder exstrophy demands patience and perseverance. It is possible
      to provide all patients with socially acceptable continence with bladder neck
      division and catheterizable continent stoma as the last resort. Urodynamic
      assessment has emerged as an essential tool in the follow-up evaluation of these
      patients. Anticholinergic medication with imipramine or oxybutinin is a useful
      adjunct in the overall management.

PMID- 21897566
TI  - Epidemiological trends of pediatric trauma: A single-center study of 791
      patients.
AB  - AIM: To assess the various epidemiological parameters that influence the
      causation of trauma as well as the consequent morbidity and mortality in the
      pediatric age group. MATERIALS AND METHODS: A prospective study of 791 patients
      of less than 12 years age, was carried out over a period of 1 year (August 2009
      to July 2010), and pediatric trauma trends, with regards to the following
      parameters were assessed: Age group, sex, mode of trauma, type of injury, place
      where the trauma occurred and the overall mortality as well as mortality.
      RESULTS: Overall trauma was most common in the school-going age group (6-12
      years), with male children outnumbering females in the ratio of 1.9:1. It was
      observed that orthopedic injuries were the most frequent (37.8%) type of
      injuries, whereas fall from height (39.4%), road traffic accident (27.8%) and
      burns (15.2%) were the next most common modes of trauma. Home was found out to be
      the place where maximum trauma occurred (51.8%). Maximum injuries happened
      unintentionally (98.4%). Overall mortality was found out to be 6.4% (n = 51).
      CONCLUSIONS: By knowing the epidemiology of pediatric trauma, we conclude that
      majority of pediatric injuries are preventable and pediatric epidemiological
      trends differ from those in adults. Therefore, preventive strategies should be
      made in pediatric patients on the basis of these epidemiological trends.

PMID- 21897567
TI  - Position of a sigmoid colon in right iliac fossa in children: A retrospective
      study.
AB  - AIM: The aim was to identify the position of sigmoid colon in children and
      discuss its clinical significance. MATERIALS AND METHODS: Ninety-one contrast
      enema studies were retrospectively evaluated and the position of sigmoid colon
      categorized as below: Left lower quadrant, right lower quadrant, midline, and
      indeterminate. RESULTS: The position of sigmoid colon in the right lower
      quadrant, left lower quadrant, midline, and indeterminate was 32 (35.16%), 33
      (36.26%), 12 (13.19%), and 14 (15.38%), respectively. There was no statistically
      significant difference in mean age (P = 0.87) or gender prevalence (P = 0.49) for
      different positions of the sigmoid colon. CONCLUSION: The sigmoid colon occupies
      the right lower quadrant in a large number of children. Awareness of this finding
      is of crucial importance in correct interpretation of abdominal radiographs in
      the emergency room.

PMID- 21897568
TI  - A helping clamp for thoracoscopic plication of eventration of the diaphragm.
AB  - BACKGROUND AND AIM: It is difficult to suture an extremely thin and billowed up
      congenital eventration of the diaphragm thoracoscopically, without insufflation.
      MATERIALS AND METHODS: The authors describe their technique using an intestinal
      clamp to control the redundant tissue and a feeding tube as a flexible knot
      pusher, to perform the thoracoscopic plication without risking hypercapnia.
      RESULTS: A satisfactory result was obtained in all the four children. CONCLUSION:
      This is a useful adjunctive for thoracoscopic plication of diaphragmatic
      eventration.

PMID- 21897569
TI  - Central venous catheterization in neonates: Comparison of complications with
      percutaneous and open surgical methods.
AB  - AIM: To compare the complications of two methods of placement of central venous
      catheters. MATERIALS AND METHODS: One hundred neonates had percutaneously
      inserted central venous catheters and another 100 had the catheters placed after
      surgical incision and vein location. RESULTS: No statistical difference was noted
      in the complication rate or efficacy CONCLUSIONS: Both the methods are equally
      safe and effective.

PMID- 21897570
TI  - Erosion of repaired exstrophy bladder by a large vesical calculus.
AB  - Formation of stones in repaired exstrophy bladder is common; however, erosion of
      stone through the repaired bladder and anterior abdominal wall has never been
      reported. We report one such case of erosion after three years of repair.

PMID- 21897571
TI  - Malignant epignathus.
AB  - Report of a neonate with a huge mass protruding from the oral cavity. The mass
      has originated from the base of the tongue. Successful excision and
      histopathological examination revealed it to be a malignant epignathus.

PMID- 21897572
TI  - Decorative crystal balls causing intestinal perforation.
AB  - Crystal jelly balls are used for decorative purpose in homes and offices. They
      swell on contact with water. We managed a patient with a clinical diagnosis of
      acute abdomen. At surgery, there was fecal peritonitis and three ileal
      perforations caused by previously ingested decorative crystal balls.

PMID- 21897573
TI  - Patent urachus with double urethra and testicular teratoma: A rare association.
AB  - In this paper, we aim to highlight a case report of a rare association of
      anomalies comprising patent urachus, double urethra and development of testicular
      teratoma.

PMID- 21897574
TI  - Renal autotransplantation in a child following renal artery stent fracture.
AB  - We report an 8-year-old child who underwent percutaneous transluminal renal
      angioplasty (PTRA) and stenting for renal artery stenosis (RAS) and later
      presented with stent fracture. Ex vivo renal artery repair and renal
      autotransplantation were successfully done.

PMID- 21897575
TI  - Use of pre and intra-operative bronchoscopy in management of bronchial injury
      following blunt chest trauma.
AB  - Blunt chest trauma resulting in right bronchial tear in an 8-year-old girl is
      reported. Use of bronchoscopy in the management of such an injury is highlighted.

PMID- 21897576
TI  - Magnetic resonance urography in duplex kidney with ectopic ureteral insertion.
AB  - This is a report on the use of magnetic resonance urography (MRU) in a 6-year-old
      girl who presented with urinary incontinence. She had a left duplex kidney with
      poorly functioning upper moiety and ectopic insertion of the dilated upper pole
      ureter. MRU has been shown to be superior to conventional imaging techniques in
      delineating poorly functioning moieties of duplex kidneys and ectopic ureters.

PMID- 21897577
TI  - Acute acalculous cholecystitis causing gall bladder perforation in children.

PMID- 21897578
TI  - Authors' reply.

PMID- 21897579
TI  - Authors' reply.

PMID- 21897580
TI  - Pediatric liver transplantation in India: The complete picture?

PMID- 21897581
TI  - Treatment of adhesive capsulitis with intra-articular hyaluronate: A systematic
      review.
AB  - Sodium hyaluronate injection into the glenohumeral joint is a treatment option in
      the management of adhesive capsulitis of the shoulder. We hypothesized that a
      systematic review would demonstrate that intra-articular sodium hyaluronate
      injections would result in significant improvements in passive range-of-motion,
      shoulder and general clinical outcome measures, and pain scales at short- and mid
      term follow-up. Multiple medical databases were searched for levels I-IV evidence
      with a priori defined specific inclusion and exclusion study criteria. Clinical
      outcome measures used included Constant score, VAS pain scores, Cho functional
      scores, JOA scores, and range-of-motion measurements. Seven studies were included
      (four Level I and three Level IV; 292 subjects, 297 shoulders). Mean subject age
      was 59.1 years and mean pre-treatment duration of symptoms was 7.3 months. 140
      subjects underwent one or multiple hyaluronate injections (120 glenohumeral
      joint; 20 subacromial bursa). Clinical follow-up was mean 9.0 weeks. Sodium
      hyaluronate injection into the glenohumeral joint has significantly improved
      shoulder range-of-motion, constant scores, and pain at short-term follow-up
      following treatment of adhesive capsulitis. Isolated intra-articular hyaluronate
      injection has significantly better constant scores than control. Isolated intra
      articular hyaluronate injection has equivalent clinical outcomes and range-of
      motion compared to intra-articular corticosteroid injection. Intra-articular
      hyaluronate injection was safe, with no reported complications within the studies
      in this review. Sodium hyaluronate injection into the glenohumeral joint is a
      safe, effective treatment in the management of adhesive capsulitis of the
      shoulder. Short-term evidence indicates that clinical outcomes are better than
      control and equivalent to intra-articular corticosteroid injection.

PMID- 21897582
TI  - Percutaneous fixation with Schanz screws for displaced two- and three- part
      fractures of the proximal humerus in patients above fifty years of age.
AB  - PURPOSE: The aim of this study is to evaluate whether two 3.0 mm Schanz screws in
      two-part proximal humeral fractures (plus one additional Schanz screw or K wire
      in three-part fractures) can provide enough stability to allow early mobilization
      until healing occurs in elderly patients. SETTINGS AND DESIGN: This prospective
      study was performed in the Orthopaedic Department of our University Hospital.
      PATIENTS AND METHODS: We performed closed reduction and percutaneous pinning for
      thirty-three patients with proximal humerus fractures. Twenty-seven patients were
      available for the final follow-up. Of those 27 patients, 17 had two-part surgical
      neck fractures; while 10 had three-part fractures. For fixation, we used two 3.0
      mm Schanz screws in patients with two-part fractures plus one additional Schanz
      screw or K wire in the 10 patients with three-part fractures. RESULTS: The mean
      Constant score modified according to the age and sex was 89.8% (range: 77.3
      97.2%). Fifteen patients had excellent results, 11 patients had good results, and
      one patient had a fair result. CONCLUSION: Closed reduction and percutaneous
      pinning with two Schanz screws for two-part surgical neck humeral fractures, plus
      an additional Schanz screw or K wire for three-part proximal humeral fractures is
      a useful and effective technique that provides enough stability to allow an early
      rehabilitation program till union occurs in elderly patients. LEVEL OF EVIDENCE:
      IV; therapeutic study, case series.

PMID- 21897583
TI  - An inexpensive reconstruction method after resection in tumors of the proximal
      humerus with extensive involvement of the diaphysis.
AB  - Limb salvage is now the norm for a large majority of malignant bone tumors. The
      proximal humerus is the third most common site for the occurrence of malignant
      tumors of bone. In tumors of the proximal humerus with large volume disease,
      extensive involvement of the diaphysis is not infrequent. Resection may often
      extend as far as the distal metaphysis in order to obtain adequate oncologic
      margins. A very small distal stump of bone poses unique challenges in
      reconstruction where conventional reconstruction modalities may be difficult to
      apply. We describe the use of a customised plate to reconstruct these defects
      which offers an inexpensive, easy to use, durable reconstruction option. It
      provides adequate shoulder and arm stability and ensures excellent hand and elbow
      motion with good functional results.

PMID- 21897584
TI  - An unusual complication of the Mackenzie approach for a Copeland
      hemiarthroplasty.
AB  - We report the case of a patient with end-stage osteoarthritis who received a
      successful Copeland resurfacing hemiarthroplasty through a Mackenzie
      anterosuperior approach, which involves taking the anterior portion of the
      deltoid attachment from the acromion along with an osteo-periosteal sleeve. The
      patient went on to develop severe subacromial impingement symptoms 4 months
      postoperatively. X-rays revealed a large anteroinferior acromial osteophyte that
      had not been present preoperatively and was deemed to represent a malunited osteo
      periosteal sleeve from the Mackenzie approach.

PMID- 21897585
TI  - Isolated avulsion fracture of lesser tuberosity of the humerus: Review of the
      literature and report of two cases.
AB  - Two cases of acute isolated avulsion fracture of the lesser tuberosity of the
      humerus and their short-term outcome are presented with a review of previously
      reported cases. Open reduction and internal fixation was performed. Outcomes were
      excellent, and the patients regained their normal pain-free shoulder function 3
      months after the operation. This was a Level IV study.

PMID- 21897586
TI  - Arthroscopic arthrodesis of the shoulder: Fourteen-year follow-up.
AB  - Shoulder arthrodesis is indicated in infections, brachial paralysis, irreparable
      rotator cuff tears, osteoarthritis without indication of prosthesis, rescue after
      arthroplasty, or after surgery for cancer. Arthroscopic arthrodesis is
      exceptional. Our aim is presenting our result after 14 years of follow-up of one
      patient. We present a case report of a 17-year-old male patient. He suffered
      fracture of left scapula (type V, Ideberg), fracture of left clavicle (type I,
      Craig), and fracture of left distal ulna. We realized osteosynthesis of clavicle
      (plate and screws) with the aim of treating this floating shoulder.
      Electromyography showed partial axonotmesis of axilar nerve. After 7 months of
      follow-up, axonotmesis was still present. We realized arthroscopic shoulder
      arthrodesis (three cannulated screws). Fourteen years later, shoulder movement
      was as follows: Flexion, 0-90 degrees ; maximum abduction, 40 degrees  with
      shoulder atrophy; Constant, 47 points; and UCLA, 17 points, without pain.
      Arthrodesis with screws reaches a subjective benefit in 82% of patients.
      Percentage of pseudarthrosis is less than in patients treated with plates,
      although the risks of infections, fractures, and material removal are greater
      than in patients treated with plates. Shoulder arthroscopic arthrodesis is
      exceptional, but it allows minimal surgical aggression.

PMID- 21897587
TI  - Blood transfusion in borderless South Asia.

PMID- 21897588
TI  - Attitude to blood donation in Saudi Arabia.
AB  - BACKGROUND AND OBJECTIVES: The blood donor system in the Kingdom of Saudi Arabia
      depends on a combination of voluntary and involuntary donors. The aim of this
      study is to explore the attitudes, beliefs and motivations of Saudis toward blood
      donation. MATERIALS AND METHODS: The study was conducted at the Donor Centers at
      King Khalid University Hospital (KKUH) Blood Bank and King Saud University
      Students Health Center, Riyadh. A self-administered questionnaire was distributed
      to donors (n = 517) and nondonors (n = 316), between February and June 2008. All
      were males. RESULTS: Ninety-nine percent of the respondents showed positive
      attitude toward blood donations and its importance for patients care, and object
      the importation of blood from abroad. Blood donors: Ninety-one percent agree that
      that blood donation is a religious obligation, 91% think no compensation should
      be given, 63% will accept a token gift, 34% do not object to donating six
      times/year and 67% did not mind coming themselves to the donor center to give
      blood. Nondonors: Forty-six percent were not asked to give blood and those who
      were asked mentioned fear (5%) and lack of time (16%) as their main deterrents.
      Reasons for rejection as donors include underweight and age (71%) and health
      reasons (19%). Seventy-five percent objected to money compensation but 69% will
      accept token gifts and 92% will donate if a relative/friend needs blood.
      CONCLUSION: These results reflect an encouraging strong positive attitude toward
      blood donation. Further future planning with emphasis on educational/publicity
      programs and careful organization of donor recruitment campaigns could see the
      dream of total voluntary nonremunerated blood donations should not take long to
      be true.

PMID- 21897589
TI  - Study of the effect of iron overload on the function of endocrine glands in male
      thalassemia patients.
AB  - BACKGROUND: Iron overload is an important issue in the state of thalassemic
      patients due to the harmful effect of high concentration of iron deposited in
      different tissues in human body including endocrine glands. In the present work,
      an attempt is carried out to estimate the effect of iron overload in thalassemic
      patients on the function of endocrine glands through the estimation of their
      ability to secrete adequate amounts of certain hormones. MATERIALS AND METHODS:
      Seventy eight male children with beta-thalassemia, in the age-group of 4-11
      years, were enrolled for this research. These children were being treated with
      frequent transfusions and long-term iron chelation therapy. Thirty age and sex
      matched children without thalassemia constituted the control group. Ferritin and
      different hormones were estimated by ELISA technique. RESULTS: The results showed
      a mild reduction in the function of endocrine glands through the decrease in the
      level of some hormones. These changes due mainly to the hypoxia and precipitation
      of iron in certain glands and overlapping with the synthesis or secretion of the
      hormones. CONCLUSION: There is a different hormonal disturbances in beta
      thalassemia patients. Reduction of total body iron store is an important goal of
      the treatment of thalassemia and measuring the hormones concentration is
      necessary for the follow up of the thalassemic patients especially during
      puberty.

PMID- 21897590
TI  - Evaluation of new cases of HCV infection in thalassaemia patients for source of
      infection.
AB  - BACKGROUND: Screening tests on blood bags is important step for blood safety. In
      Iran, screening for HCV started from 1996. We decided to determine the new cases
      of hepatitis C in our thalassemic patients, after screening of blood bags was
      initiated and trace backing from recipients to find their donors. MATERIALS AND
      METHODS: The study was done on patients with complete files for HCVAb test
      results. Only cases that had a positive HCVAb result following a negative result
      were considered as new cases. For trace backing, we recorded the blood
      transfusions' date and the blood bags' number from last negative test results
      (HCVAb) to the first positive test result. These data were sent to the
      transfusion center. The suspected donors were contacted and asked to be tested
      again in the transfusion center. RESULTS: A total of 395 patients were studied;
      229 (58%) males and 166 (42%) females. Mean age was 27.5 years. We had 109 HCV
      (27.5%) positive cases of whom 21 were infected after 1996. We traced the last
      five cases contaminated during 2003 and 2004. These five patients had 13, 10, 13,
      12, and 6 donors, respectively (totally 54 donors were found). We proved the
      healthy state in 68.5% (37 of 54) of our donors population. Of them, 81% were
      repeated donors and 17 of 54 donors (31.5%) could not be traced (because of
      change in addresses). We did not have any HCV new cases after 2004. CONCLUSION:
      We could not prove HCV transmission from donors as the source of infection.
      Although parenteral transmission is always on top of the list in HCV infection,
      the possibility of hospital and/or nursing personnel transmission and/or patient
      to-patient transmission such as use of common instruments like subcutaneous
      Desferal((r)) infusion pumps; which the patients used for iron chelation therapy,
      should also be kept in mind.

PMID- 21897591
TI  - Seroprevalence of subclinical HEV infection in asymptomatic, apparently healthy,
      pregnant women in Dakahlya Governorate, Egypt.
AB  - BACKGROUND AND AIM: Hepatitis E virus (HEV) is a major public health problem in
      the developing countries. HEV infection in pregnant women is more common and
      fatal in the third trimester. The present study was designed to determine the
      seroprevalence of subclinical HEV infection in asymptomatic pregnant women.
      MATERIALS AND METHODS: A total of 116 asymptomatic pregnant women divided into 2
      groups: Group 1 included 56 pregnant women with HCV positive serology and group 2
      included 60 pregnant women with negative HCV serology were included in this
      study. Prevalence of anti-HEV antibodies and anti-HCV were determined by an
      enzyme linked immunosorbent assay (ELISA) kit. RESULTS: The overall prevalence of
      anti-HEV IgG was highly significant among pregnant women with chronic HCV
      infection 40/56 (71.42%) than pregnant women free from chronic HCV infection
      28/60 (46.7%) (P = 0.006). Chronic HCV infection in pregnant women appeared to be
      a risk factor associated with HEV IgG seropositivity (OR = 2.86, CI = 1.24-6.6).
      The seropositivity of anti-HEV IgG was significantly high in rural areas than
      urban areas (62.5% vs. 37.5%) in group 1 and (78.58% vs. 21.42%) in group 2 (P =
      0.15) and OR = 2.2, CI = 0.65-7.7). A decrease in albumin level (P = 0.047) and
      an increase in bilirubin (P = 0.025), ALT (P = 0.032), and AST (P = 0.044) in
      pregnant women with positive HCV and IgG anti-HEV than the second group with
      negative HCV serology. CONCLUSIONS: The seroprevalence of anti-HEV IgG in
      pregnant women is high in Egypt especially in rural areas. With chronic HCV
      coinfection, a marked increase in anti-HEV IgG seropositivity and significant
      worsening of the biochemical liver indices were noted. Increased public awareness
      about the sound hygienic measures for a less prevalence of HEV is strongly
      advised. The need for HEV vaccination for those at risk, especially pregnant
      ladies, should be considered.

PMID- 21897592
TI  - Serological study on parvovirus B19 infection in multitransfused thalassemia
      major patients and its transmission through donor units.
AB  - BACKGROUND: Human parvovirus B19 (B19) virus is a newly recognized agent for
      transfusion transmitted diseases. Beta-thalassemia major patients receive a
      hypertransfusion regimen, hence, are prone to acquire B19 infection; moreover,
      B19 escapes viral inactivation methods and donor units are not tested for B19,
      but there are just a couple of studies globally and none from the Asian
      continent. Hence, a study was designed to find the frequency of B19 infection and
      its transmission in multitransfused thalassemia patients. MATERIALS AND METHODS:
      Ninety multitransfused beta-thalassemia major (thalassemia) patients, 32 controls
      (age, sex matched) without any history of transfusion were enrolled. Besides the
      donor units were tested in B19 un-infected patients. B19 specific IgG and IgM
      antibodies in the sera were analyzed by ELISA (in-house), using B19 VPI and VP2
      recombinant and purified antigens; additionally HBsAg and anti-HIV and anti-HCV
      antibodies were tested for coexisting infections. RESULTS: Seventy-three (81%)
      thalassemia patients tested positive for anti-B19 IgG antibodies as compared to
      seven (21%) in the controls group (P < 0.01), while anti-B19 IgM antibodies were
      detected in 37 (41.1%) compared to two (6.2%) in the controls (P < 0.01). Mean
      age of the thalassemia patient was eight years (range 2 - 18 years) and B19
      infection was highest in the six-to-ten year range. Seropositivity increased with
      the number of transfusions. Two of the four HBsAg positive and five of the seven
      anti-HCV IgM antibody-positive patients also had anti-B19 IgM. After a six-month
      follow-up, four (25%) of the 16 seronegative patients seroconverted and anti-B19
      IgM antibodies were detected in their donor units. CONCLUSIONS: Most of
      multitransfused thalassemics were B19 seropositive or had anti-B19 IgM; in the
      remaining uninfected group, B19 got transmitted through infected / IgM-positive
      donor units.

PMID- 21897594
TI  - The Rh allele frequencies in Gaza city in Palestine.
AB  - BACKGROUND: The Rh blood group system is the second most clinically significant
      blood group system. It includes 49 antigens, but only five (D, C, E, c and e) are
      the most routinely identified due to their unique relation to hemolytic disease
      of the newborn (HDN) and transfusion reactions. Frequency of the Rh alleles
      showed variation, with regard to race and ethnic. OBJECTIVES: The purpose of the
      study was to document the Rh alleles' frequencies amongst males (M) and females
      (F) in Gaza city in Palestine. MATERIALS AND METHODS: Two hundred and thirty-two
      blood samples (110 M and 122 F) were tested against monoclonal IgM anti-C,anti-c,
      anti-E, anti-e and a blend of monoclonal/polyclonal IgM/IgG anti-D. The expected
      Rh phenotypes were calculated using gene counting method. RESULTS: The most
      frequent Rh antigen in the total sample was e, while the least frequent was E.The
      order of the combined Rh allele frequencies in both M and F was CDe > cDe > cde >
      CdE > cDE > Cde > CDE. A significant difference was reported between M and F
      regarding the phenotypic frequencies (P < 0.05). However, no significance (P >
      0.05) was reported with reference to the observed and expected Rh phenotypic
      frequencies in either M or F students. CONCLUSION: It was concluded that the Rh
      antigens, alleles and phenotypes in Gaza city have unique frequencies, which may
      be of importance to the Blood Transfusion Center in Gaza city and anthropology.

PMID- 21897593
TI  - Distribution of Hepatitis B virus genotypes among healthy blood donors in eastern
      part of North India.
AB  - AIM: We evaluated the distribution HBV genotypes among non-remunerated healthy
      blood donors in eastern North India. MATERIALS AND METHODS: During screening of
      donated blood, 176 consecutive HBsAg positive, samples comprised the study. HBV
      DNA was quantitative detected in 150 samples by PCR. HBV genotype was determined
      by identifying genotype-specific DNA band using nested PCR. RESULTS: Majorities
      were of age group 31-40 yrs (65.3%). Males (92.7%) outnumbered females (7.3%) and
      were HbeAg-negative HBsAg carriers. Over all, genotype-A was the most prevalent
      (54%) followed by D (21.3%). We did not find genotype-G and H. Districts under
      study, divided into four zones: Zone-I genotype-A was most common (62.3%)
      followed by D (18.8%); Zone-II genotype-C (41.2%) was more frequent followed by D
      (20.6% and A (17.7%). Zone-III in adjoining Bihar state close to Zone-I, A was
      more prevalent (81.8%) followed by B and C (9.1%). In Zone-IV adjoining Zone- II
      had genotype-A (100%) only. Genotype-D had more sporadic distribution. Genotype-E
      and F were prevalent in Zone I and II (3/150, 2%). CONCLUSIONS: Among blood
      donors HBV genotype-A followed by D was the most prevalent in eastern North
      India. Genotype-A had pattern of distribution signifying common focus, while D
      was more sporadic and C had single large pocket (Zone-II) probably common focus
      but restricting to particular area. Evidences are suggestive of association of
      HBV genotype in liver dysfunction. An effective treatment and preventive
      strategies based of genotypes will reduce the disease burden and increase the
      blood safety.

PMID- 21897595
TI  - Type and screen policy in the blood bank: Is AHG cross-match still required? A
      study at a multispecialty corporate hospital in India.
AB  - BACKGROUND: Antibodies against only about 25-28 blood group antigens are known to
      cause hemolytic reactions (HTRs), and red cell antibody screening should detect
      such clinically significant antibodies. An extension of the antibody screening
      test is the 'type and screen' done to detect clinically significant antibodies,
      omiting the anti-human globulin (AHG) cross-match. AIM: The aim of this study was
      to find out if the type and screen procedure is a safe method for pre-transfusion
      testing when compared to the AHG cross-match currently in use in India. MATERIALS
      AND METHODS: We evaluated data from 45373 patients for whom a total of 61668
      units of packed red blood cells (PRBC) were cross-matched in the AHG phase using
      DiaMed((r)) ID cards. An antibody screen was carried out in all the patients
      using the DiaMed((r)) ID-DiaCell I+II+III. The AHG cross-match was also carried
      out for all recipients, irrespective of the result of the antibody screen. The
      results were compared to see if there were any cases where the antibody screening
      was negative but the AHG cross-match showed incompatibility. RESULTS: Not a
      single case was found where the antibody screen was negative and AHG cross-match
      showed incompatibility. In 68 cases the antibody screening was positive. Out of
      the 68 cases, AHG cross-match was incompatible with at least one unit of PRBC in
      41 cases. CONCLUSION: The screening cell panel adequately detected the clinically
      significant antibodies in the Indian population in our study. The type and screen
      policy can be safe, efficient, cost-effective, and beneficial to the transfusion
      service in India.

PMID- 21897596
TI  - Safety of type and screen method compared to conventional antiglobulin crossmatch
      procedures for compatibility testing in Indian setting.
AB  - BACKGROUND: Over the past 30 years, pretransfusion tests have undergone
      considerable modification. In 1984, AABB recommended that the full cross match
      could be replaced by an abbreviated cross match in patients with negative
      antibody screen. However, before implementation of such a policy, issue regarding
      safety of T & S needs to be evaluated. OBJECTIVES: The aim of pretransfusion
      testing (PTT) is to ensure that enough red blood cells (RBCs) in the selected red
      cell components will survive when transfused. RESULTS AND CONCLUSION: We have,
      therefore in this study; evaluated safety of T & S procedure for PTT in
      comparison with conventional test tube cross match. The T & S procedure gave a
      safety of 91.6%. Also, the usefulness of the T & S was shown through the
      detection of unexpected antibodies in 0.75% (15 out of 2026) of cases.

PMID- 21897597
TI  - In vitro function of random donor platelets stored for 7 days in composol
      platelet additive solution.
AB  - BACKGROUND AND AIM: Platelets are routinely isolated from whole blood and stored
      in plasma for 5 days. This study was done to assess the in vitro function of
      random donor platelets stored for 7 days in composol platelet additive solution
      at 22 degrees C. MATERIALS AND METHODS: The study sample included 30 blood donors
      of both sex in State Blood Bank, C S M Medical University, Lucknow. Random donor
      platelets were prepared by the platelet-rich plasma method. Whole blood (350 ml)
      was collected in anticoagulant Citrate Phosphate Dextrose Adenine triple blood
      bags. Random donor platelets were stored for 7 days at 22 degrees C in platelet
      incubators and agitators with and without additive solution. RESULTS: Platelet
      swirling was present in all the units at 22 degrees C on day 7 with no evidence
      of bacterial contamination. Comparison of the mean values of platelet count,
      platelet factor 3, lactate dehydrogenase, pH, glucose and platelet aggregation
      showed no significant difference in additive solution while platelet factor 3,
      glucose and platelet aggregation showed significant difference (P < 0.001) on day
      7 without additive solution at 22 degrees C. CONCLUSION: Our study infers that
      the platelet viability and aggregation were the best maintained within normal
      levels on day 7 of storage in platelet additive solution at 22 degrees C. Thus,
      we may conclude that in vitro storage of random donor platelets with an extended
      shelf life of 7 days using platelet additive solution may be advocated to improve
      the inventory of platelets.

PMID- 21897598
TI  - Transfusion-related adverse events at the tertiary care center in North India: An
      institutional hemovigilance effort.
AB  - AIM: This study was designed to analyze the incidence and spectrum of adverse
      effects of blood transfusion so as to initiate measures to minimize risks and
      improve overall transfusion safety in the institute. MATERIALS AND METHODS:
      During the period from July 2002 to July 2003 all the adverse events related to
      transfusion of blood and blood components in various clinical specialties were
      recorded. They were analyzed and classified on the basis of their clinical
      features and laboratory tests. Attempt was also made to study the predisposing
      risk factors. RESULTS: During the study period 56,503 blood and blood components
      were issued to 29,720 patients. A total of 105 adverse reactions due to
      transfusion were observed during the study period. A majority of the adverse
      reactions was observed in hemato-oncology patients 43% (n = 45) and in
      presensitized patient groups 63% (n = 66). FNHTR 41% (n = 43) and allergic
      reactions 34% (n = 36) were the most common of all types of adverse transfusion
      reactions, followed by AcHTR 8.56% (n = 9). Majority of these AcHTR were due to
      unmonitored storage of blood in the refrigerator of wards resulting in hemolysis
      due to thermal injury. Less frequently observed reactions were anaphylactoid
      reactions (n = 4), bacterial sepsis (n = 4), hypervolemia (n = 2), hypocalcemia
      (n = 2), TRALI (n = 1), DHTR (n = 1), and TAGvHD (n = 1). CONCLUSION: Analysis of
      transfusion-related adverse outcomes is essential for improving safety. Factors
      such as improvement of blood storage conditions outside the blood bank,
      improvement in cross-matching techniques, careful donor screening, adherence to
      good manufacturing practices while component preparation, bedside monitoring of
      transfusion, and documentation of adverse events will help in reducing
      transfusion-related morbidity and mortality.

PMID- 21897599
TI  - The quest for an Indian blood law as of blood transfusion services regulatory
      framework.
AB  - BACKGROUND: Blood transfusion services are a vital part of the national health
      delivery system. The responsibility for ensuring a continuous supply of blood
      rests with health administrators, who need to galvanize entire communities
      towards regular and non-remunerated blood donation. OBJECTIVE: The present study
      aimed to examine the prevailing global regulations and practices related to blood
      transfusion and press the case for a dedicated blood law in India. MATERIALS AND
      METHODS: We attempted a comprehensive, annotated assembly of published studies on
      blood transfusion services in India. DATA ABSTRACTION AND SYNTHESIS: Laws related
      to blood transfusion services exist in India as a part of the Drugs and Cosmetics
      Law. In the developed world, most blood donors are unpaid volunteers who give
      blood for a community supply. In order to augment safe blood transfusion services
      in India, we have to develop operational legal guidelines on recruitment and
      retention of voluntary blood donors to direct related organizations for this
      imperative activity. CONCLUSION: Several factors, such as political will and a
      professional and ethical approach can help in formulating a common vision,
      building trust, by providing optimum information towards a social movement for
      the rational blood transfusion services. We have to come together for a dedicated
      blood law in order to improve the quality of blood transfusion services in India.

PMID- 21897600
TI  - White particulate matter in a packed red blood cells unit.

PMID- 21897601
TI  - Prevalence and trends of transfusion transmitted infections in a regional blood
      transfusion centre.

PMID- 21897602
TI  - Severe anaphylactic reaction in IgA deficient patient following transfusion of
      whole blood.

PMID- 21897603
TI  - YMDD motif mutation after lamivudine therapy.

PMID- 21897604
TI  - Re: Heparin-induced thrombocytopenia - Type 2.

PMID- 21897605
TI  - Thrombotic thrombocytopenic purpura treated with vincristine in a Jehovah's
      witness.

PMID- 21897606
TI  - Analysis of the trend of hepatitis B, hepatitis C, HIV, syphilis, and malaria
      infections in a rural part of West Bengal.

PMID- 21897607
TI  - Para-Bombay: A blind spot in blood grouping?

PMID- 21897608
TI  - Psychosocial profiling of blood donors and assessing source of awareness of blood
      donation through a blood donation camp at a medical college, Ahmadabad, Gujarat.

PMID- 21897609
TI  - Regular repetitive voluntary blood donors: What're their characteristics ?

PMID- 21897610
TI  - Contribution of religion to blood donation: Iran experience.

PMID- 21897611
TI  - The culprits behind a hyper-intense spleen.

PMID- 21897612
TI  - Idiopathic thrombocytopenic purpura coexisting with polycythemia vera.

PMID- 21897613
TI  - Massive pulmonary embolism and cardio-pulmonary resuscitation leading to
      disseminated intravascular coagulation.

PMID- 21897614
TI  - Strategies adopted to overcome dengue crisis at a hospital based blood bank.

PMID- 21897615
TI  - Attitudes and communication skills.

PMID- 21897616
TI  - A case of severe intravascular hemolysis in a young girl.

PMID- 21897617
TI  - Genetics of myopia.

PMID- 21897618
TI  - A review on recent advances in dry eye: Pathogenesis and management.
AB  - Keratoconjunctivitis sicca, more commonly known as dry eye, is an extremely
      common and often unrecognized disease. It is the condition in ophthalmology that
      in its mild grade of severity will affect most of the population at one time or
      other. Due to a wide variety of presentations and symptoms, it often frustrates
      the ophthalmologists as well as patients. Due to multifactorial and elusive
      etiology, it is often challenging to treat dry eye. Ocular surface disorders are
      also clinically important to treat especially in terms of visual acuity. Xero
      dacryology is therefore becoming a very important branch of ophthalmology. Recent
      studies have given insight into the inflammatory etiology of dry eye. The
      conventional and main approach to the treatment of dry eye is providing
      lubricating eye drops or tear substitutes. However, the newer treatment approach
      is to target the underlying cause of dry eye instead of conventional symptomatic
      relief. In light of the above knowledge, the present article focuses on newer
      theories on pathogenesis of dry eye and their impact on dry eye management.
      METHOD OF LITERATURE SEARCH: A systematic literature review was performed using
      PubMed databases in two steps. The first step was oriented to articles published
      for dry eye. The second step was focused on the role of inflammation and anti
      inflammatory therapy for dry eye. The search strategy was not limited by year of
      publication. A manual literature search was also undertaken from authentic
      reference books on ocular surface disease.

PMID- 21897619
TI  - Association of vitamin D receptor gene start codon (Fok1) polymorphism with high
      myopia.
AB  - BACKGROUND: High myopia caused primarily due to abnormal emmetropization and
      excessive axial ocular elongation is associated with sight-threatening ocular
      pathology. Muscular dysfunction of ocular ciliary muscles due to altered
      intracellular calcium levels can result in defective mechanotransduction of the
      eye and retinal defocus. The vitamin D3 receptor (VDR; a intracellular hormone
      receptor) is known to mediate calcium homeostasis, influencing the development of
      myopia. MATERIALS AND METHODS: In the present study, a total of 206 high myopia,
      98 low myopia and 250 control samples were analyzed for VDR gene Fok1 (exon 2
      start codon) polymorphism using polymerase chain reaction-restriction fragment
      length polymorphism (PCR-RFLP) technique. RESULTS: High myopia patients revealed
      decrease in the frequency of ff homozygotes (8.3%) as compared to control group
      (14.0%), with a corresponding increase in frequency of FF homozygotes (68.9% in
      high myopia vs. 62.8% in controls). The frequency of f allele carriers (Ff and
      ff) was increased in females of high myopia (35.6%) and low myopia cases (45.4%).
      Elevated frequency of f allele was found only in early age at onset cases of high
      myopia (0.227) and later age at onset (10-20 years) cases of low myopia (0.273)
      as well as in low myopia cases with parental consanguinity (0.458) (P 0.035;
      chi(2) = 6.692*). CONCLUSION: The results suggest that VDR gene might not be
      playing a direct role in the development of myopia, but might contribute
      indirectly to the risk conferred by mechanical stress factors or
      growth/development related factors through its role in calcium homeostasis and
      regulation of ciliary muscle function.

PMID- 21897620
TI  - Half-fluence photodynamic therapy to treat chronic central serous
      chorioretinopathy: A case series.
AB  - OBJECTIVE: To evaluate the efficacy and safety of half-fluence photodynamic
      therapy (PDT) in treating chronic central serous chorioretinopathy (CSC) in Omani
      population. MATERIALS AND METHODS: A Retrospective chart review of all patients
      with chronic CSC treated with half-fluence PDT from November 2009 to December
      2010 was carried out. Recorded parameters included best-corrected visual acuity,
      findings of clinical examination, results of fluorescein angiography and optical
      coherence tomography at baseline and during follow-up visits after treatment.
      RESULTS: Six eyes (of five Omani patients) with chronic CSC, of at least 9 months
      duration, were treated with half-fluence PDT. All eyes showed a complete
      resolution of CSC within 1 month following treatment. Four eyes showed visual
      improvement and two had unchanged stable vision. No complications from the
      treatment were noticed during the follow-up visits. CONCLUSION: Half-fluence PDT
      to treat chronic CSC in Omani population is a promising treatment that results in
      both structural and functional improvement.

PMID- 21897621
TI  - Amniotic membrane transplantation: An option for ocular surface disorders.
AB  - BACKGROUND: Ocular surface disorders (OSD) are challenging to treat. They can
      introduce serious morbidity and might even lead to visual loss. In such
      situations, keratoplasty remains the last option. Amniotic membrane
      transplantation (AMT) has been shown to be effective in the management of ocular
      surface pathologies. The aim of the study was to assess the efficacy of AMT for
      various indications of OSD. MATERIALS AND METHODS: Experience of AMT in 65
      patients with different OSD was evaluated. The aim of AMT was to achieve
      symptomatic relief, reduced inflammation, recurrence, and corneal haze; improve
      epithelization, stromal healing and visual acuity; and delay keratoplasty. Fresh
      amniotic membrane was used in all cases by a single surgeon. Follow-up and
      observations were done to evaluate success of achieving the goal. RESULTS:
      Indications for AMT included primary and recurrent pterygium, various types of
      corneal ulcers (non-healing ulcer, descemetocele, corneal thinning and
      perforation), spheroidal degenerations, chemical burn and bullous keratopathy.
      The aim of AMT was different in different etiological indications. Postoperative
      follow-up was between 6 and 18 months. Success and complication rate were
      observed. Symptomatic relief (reduced pain and redness) was seen in patients with
      various corneal ulcers, chemical burn and bullous keratopathy. Improved
      epithelialization and stromal healing was noted in corneal ulcer cases. In
      spheroidal degenerations, keratectomy with AMT improved vision. Recurrence of
      pterygium was low (4.61%); graft failure in the form of graft rejection was seen
      in only 3.07% cases of acute keratitis. Corneal vascularization (4.61%) was
      present but not severe enough to hamper vision. Success in gaining intended
      effect was the most significant result with AMT. CONCLUSION: AMT in various
      ocular surface pathologies shows success in achieving the goal of symptomatic
      relief, improved epithelialization, stromal healing and vision. Reduction in
      inflammation, corneal haze and recurrence of original disease is achieved with
      minimum complications.

PMID- 21897622
TI  - Patient satisfaction regarding eye care services at tertiary hospital of central
      India.
AB  - PURPOSE: To evaluate patients' satisfaction regarding eye care services and
      suggest policy changes accordingly. STUDY DESIGN: Descriptive study. MATERIALS
      AND METHODS: This study was conducted between September 2005 and June 2006.
      Patients attending the eye clinic of Sadguru Netra Chikitsalaya, Chitrakoot,
      Madhya Pradesh, India, and admitted as in-patients in this hospital were our
      study population. Randomly selected patients were interviewed by trained staff.
      Close-ended questionnaire was used to conduct these structured interviews. Their
      responses were grouped into one of five categories and evaluated to determine
      satisfaction for different components of eye care services. RESULTS: Three
      hundred and twenty persons were interviewed. The satisfaction was of excellent
      grade among 77 (48.1%) patients attending clinic and 156 (97.5%) patients who
      were admitted in the hospital. The participants expressed dissatisfaction for the
      long waiting period in clinics, poor cleanliness, and insufficient toilet
      facilities. Those admitted in the hospital felt that food facilities were less
      than the expected quality. Child-friendly facilities received high satisfaction
      scores. CONCLUSION: Although eye care services both in clinics and in the wards
      were satisfactory according to the end-users, there are scopes for improvement.
      Patient satisfaction surveys should be encouraged in hospitals for better
      accountability and also for strengthening the quality of eye care services.

PMID- 21897623
TI  - Awareness of retinopathy of prematurity among pediatricians in a tier two city of
      South India.
AB  - PURPOSE: To analyze the level of awareness and knowledge about retinopathy of
      prematurity (ROP) among pediatricians in Coimbatore, which is a tier two city in
      South India. MATERIALS AND METHODS: A questionnaire was framed on the knowledge
      attitude and practice (KAP) pattern. The questionnaire was given to 83 practicing
      pediatricians in government and private practice in Coimbatore and collected in
      person between November and December 2009. Answers were obtained on criteria like
      knowledge, prevention, screening, treatment and awareness of ROP. RESULTS: Only
      54 (65.1%) pediatricians were aware of ROP, while 29 (34.9%) were not aware of
      the disease. Thirty-three (39.8%) answered that ROP is preventable, while 24
      (28.9%) responded that ROP is not preventable. Thirty-four (41%) pediatricians
      had no idea as to which part of the eye is affected in ROP, while 38 (45.8%) did
      not know when ROP screening should be started. Only 43 (51.8%) pediatricians were
      sure that ROP is treatable. Pediatricians in private hospitals were more aware of
      ROP compared to their counterparts in government hospitals (P = 0.006).
      CONCLUSION: Awareness among pediatricians in Coimbatore about ROP is poor. Our
      study emphasizes the need to increase awareness of this avoidable cause of
      blindness.

PMID- 21897624
TI  - Atypical retinocytoma with diffuse vitreous seeds: An insight.
AB  - Retinocytoma is a rare benign form of retinoblastoma. It is usually found on
      routine examinations and also while screening families of patients with
      retinoblastoma. Distinctive features are a translucent retinal mass with
      calcification, retinal pigment epithelial disturbance, chorioretinal atrophy and
      absence of growth. We report a case with all the above features along with
      diffuse vitreous seeds and optical coherence tomographic documentation of
      intralesional cavitary lesions.

PMID- 21897625
TI  - Reactive macular edema and acute visual loss after photodynamic therapy on the
      same day of fluorescein angiography.
AB  - Reactive macular edema can occur following photodynamic therapy (PDT) in patients
      who have undergone fluorescein angiography (FA) on the same day. It might be
      better not to perform PDT on the same day of FA to avoid side effects. The safety
      interval between FA and PDT should be at least 24 hours, considering fluorescein
      retention in the body.

PMID- 21897626
TI  - Fraser syndrome in three consecutive siblings.
AB  - Fraser syndrome (FS) is a rare disorder characterized by a combination of
      acrofacial and urogenital malformations with or without cryptophthalmos. We
      report a newborn and its two elder siblings who had multiple congenital anomalies
      and clinico-radiological features consistent with FS.

PMID- 21897627
TI  - Macrostriae and Descemet's membrane folds in the Descemet's stripping endothelial
      keratoplasty graft.

PMID- 21897628
TI  - Congenital sixth nerve palsy or Type I Duane syndrome?

PMID- 21897629
TI  - Macular dystrophy in a young male with corneal dystrophy among sisters.

PMID- 21897630
TI  - Primary sebaceous gland carcinoma of the bulbar conjunctiva without involvement
      of eyelid: A clinical dilemma.
AB  - Sebaceous gland carcinoma usually arises from the meibomian or Zeis glands within
      the eyelid, but tumor arising primarily from the conjunctiva, especially bulbar
      conjunctiva, is a rarity. We hereby report a case of a 50-year-old female who
      presented with a painless mass in the inferior limbus, encroaching the cornea and
      hanging over the lower eyelid without involving it. Imprint cytology was
      suggestive of adenosquamous carcinoma. Management consisted of wide local
      excision, cryotherapy to tumor bed, and topical 5-fluorouracil (5-FU) 1%
      preoperatively and postoperatively. Histopathologic analysis was in favor of
      sebaceous gland carcinoma. This case suggests that although sebaceous gland
      carcinoma commonly originates as a lid tumor, it can present as a bulbar
      conjunctival mass. Topical 5-FU is a viable and efficient cost-effective
      alternative for neo-adjuvant and adjuvant treatment of sebaceous gland carcinoma.

PMID- 21897631
TI  - "ABC" of costing of cataract surgeries.

PMID- 21897632
TI  - Bruckner's test as a screening modality for anisometropia and strabismus.

PMID- 21897633
TI  - Isolated optic nerve infiltration as a site of relapse of acute lymphoblastic
      leukemia.

PMID- 21897635
TI  - [Not Available].

PMID- 21897634
TI  - Assessment of a modification of Bruckner's test as a screening modality for
      anisometropia and strabismus.

PMID- 21897636
TI  - Exploring the possible mechanisms of action behind the antinociceptive activity
      of Bacopa monniera.
AB  - AIM: Earlier studies have demonstrated that Bacopa monniera (BM), a plant
      described in Ayurveda for many CNS actions was found to exhibit antidepressant
      (methanolic extract at 20mg/kg and 40mg/kg p.o.) as well as antinociceptive
      activity (aqueous extract (AE) at 80 mg/kg, 120 mg/kg and 160 mg/kg p.o.). The
      present study sought to explore the possible mechanisms of antinociceptive
      effects of aqueous extract of Bacopa monniera (AEBM) at 80 mg/kg, 120 mg/kg and
      160 mg/kg given orally. MATERIALS AND METHODS: AEBM was given singly as well as
      with selective alpha2 receptor blocker Yohimbine, selective beta1 receptor
      blocker Atenolol, serotonin receptor antagonist Cyproheptadine and a non
      selective opioid receptor antagonist naloxone in experimental groups of mice and
      rats under strict protocols and conditions. RESULTS: We observed that the
      antinociceptive effects of AEBM in the acetic acid writhing test was prevented by
      prior treatment with the selective Yohimbine (1 mg/kg, i.p; 14.50 +/- 2.26 and
      37.17 +/- 2.14 writhes in the AEBM-treated and yohimbine pre-treated AEBM groups,
      respectively) and selective beta1 Atenolol receptor blocker (1 mg/kg, i.p; 14.50
      +/- 2.26 and 31.00 +/- 5.44 writhes in the AEBM-treated and yohimbine pre-treated
      AEBM groups, respectively). In the formalin test, the reduction in licking time
      with AEBM was found to be reversed by prior treatment with serotonin receptor
      antagonist Cyproheptadine (1 mg/kg, i.p; 47.33 +/- 2.25s and 113.50 +/- 3.83s
      (during phase I i.e. 0-5 min) and 26.67 +/- 3.83s and 88.17 +/- 7.27s (during
      phase II i.e. 20-30 min) in the AEBM-treated and Cyproheptadine pre-treated AEBM
      groups, respectively). The % increase in tail flick latency with AEBM was
      prevented by prior treatment with the non-selective opioid receptor antagonist
      naloxone (2mg/kg, i.p; 282.35 and 107.35 in the AEBM-treated and naloxone-treated
      groups, respectively). CONCLUSIONS: Our results indicate, that the endogenous
      adrenergic, serotonergic and opioidergic systems are involved in the analgesic
      mechanism of action of the aqueous extract of Bacopa monniera.

PMID- 21897637
TI  - The efficacy of Ayurvedic treatment for rheumatoid arthritis: Cross-sectional
      experiential profile of a longitudinal study.
AB  - CONTEXT: Allopathic and Ayurvedic physicians collaborated on a study of
      traditional medicine, which was sponsored by the World Health Organization. AIMS:
      The aim of the study was to test the efficacy and safety of Ayurvedic treatment
      for rheumatoid arthritis (RA). SETTINGS AND DESIGN: This study was conducted at
      the Ayurvedic Trust, Coimbatore, India. MATERIALS AND METHODS: In this unique
      study of classical Ayurvedic treatment for RA, allopathic physicians enrolled a
      total of 290 patients with a confirmed diagnosis of RA over a 7-year period, and
      once every 6 weeks evaluated Ayurvedic treatment outcomes on the basis of
      American Rheumatism Association criteria: grip strength, walking time, number of
      swollen and painful joints, joint count, functional class, erythrocyte
      sedimentation rate, and rheumatoid factor. Ayurvedic physicians administered
      individualized treatment, closely adhering to principles set forth in classical
      Ayurvedic texts. The duration of treatment varied from 1 to 6 months. STATISTICAL
      ANALYSIS USED: Due to limitations in computer technology in the 1970s, the data
      were not computerized. Therefore, data for 12 months at a time were analyzed,
      using repeated measures t-test. Measures of central tendency (means) and
      probability values were reported. Results from the patients enrolled and
      discharged at the end of the first year of the study (N = 33) are presented in
      this paper. RESULTS: There was statistically significant improvement in all
      parameters from admission to discharge. CONCLUSIONS: The results indicated that
      classical Ayurvedic treatment was effective in this first cohort of patients who
      completed treatment. Even patients with severe functional limitations showed
      significant improvement. Although there was no control group, the results are
      positive enough to warrant further study of classical Ayurvedic treatment for RA
      in controlled trials.

PMID- 21897638
TI  - Blood compatibility studies of Swarna bhasma (gold bhasma), an Ayurvedic drug.
AB  - Swarna bhasma (gold bhasma) preparations are widely utilized as therapeutic
      agents. However, in vitro biological evaluations of bhasma preparations are
      needed along with the physicochemical characterization for present day
      standardization of metallic bhasma preparations to meet the criteria that
      supports its use. Therefore, an attempt has been made to evaluate the protein
      adsorption, blood compatibility and complement activation potential of two
      batches of Swarna bhasma preparation, along with its physicochemical
      characterization. The particle size, morphology, elemental analysis, and in vitro
      cytotoxicity were evaluated initially. Red blood cell hemolysis, aggregation
      studies with blood cells, protein adsorption, complement C3 adsorption, platelet
      activation and tight junction permeability in Caco-2 cell line were investigated.
      The Swarna bhasma preparations with a crystallite size of 28-35 nm did not induce
      any blood cell aggregation or protein adsorption. Activation potential of these
      preparations towards complement system or platelets was negligible. These
      particles were also non-cytotoxic. Swarna bhasma particles opened the tight
      junctions in Caco-2 cell experiments. The results suggest the application of
      Swarna bhasma preparations as a therapeutic agent in clinical medicine from the
      biological safety point of view.

PMID- 21897639
TI  - Evaluation of antioxidant potential of Amalakayas Rasayana: A polyherbal
      Ayurvedic formulation.
AB  - Amalakayas Rasayana (AR) is a polyherbal formulation mentioned in Ayurveda to
      treat aging and age-associated diseases. Being an antiaging drug, AR may have
      antioxidants and free radical scavenging activity to minimize free radical
      induced damage which is a key cause of aging. The methanolic extract of AR was
      evaluated in vitro for total phenolic and tannin content, free radical scavenging
      activity, superoxide radical scavenging activity, and reducing power. The total
      phenolic content was measured using Folin-ciocalteu reagent against gallic acid
      [relative standard deviation (R(2)) = 0.998]. Total tannin was estimated using
      the Stephen method and was found to be 2.82% w/w. Free radical scavenging
      activity was measured by 2,2-diphenyl-1-picryl hydrazyl assay and R(2) was 1.
      Superoxide radical scavenging activity was done by ethylene diamine tetra acetate
      and Nitro Blue Tetrazolium Chloride assays against ascorbic acid and R(2) was
      0.976 (EC(50)= 77.5 MUg/ml). Ferrous reducing power was evaluated by Oyaizu
      method where R(2) was 0.986. All studies showed that AR possesses antioxidant
      activity. The results of this study suggest that the antioxidant and free radical
      scavenging activity of AR may explain its rasayana effect and justify its use as
      a medicine for age associated diseases.

PMID- 21897640
TI  - The effect of Triphala and Chlorhexidine mouthwash on dental plaque, gingival
      inflammation, and microbial growth.
AB  - The objective of this study was to ascertain the effects of a mouthwash prepared
      with Triphala on dental plaque, gingival inflammation, and microbial growth and
      compare it with commercially available Chlorhexidine mouthwash. This study was
      conducted after ethics committee approval and written consent from guardians (and
      assent from the children) were obtained. A total of 1431 students in the age
      group 8-12 years, belonging to classes fourth to seventh, were the subjects for
      this study. The Knowledge, Attitude and Practice (KAP) of the subjects was
      determined using a questionnaire. The students were divided into three groups
      namely, Group I (n = 457) using Triphala mouthwash (0.6%), Group II (n = 440)
      using Chlorhexidine mouthwash (0.1%) (positive control), and Group III (n = 412)
      using distilled water (negative control). The assessment was carried out on the
      basis of plaque scores, gingival scores, and the microbiological analysis
      (Streptococcus and lactobacilli counts). Statistical analysis for plaque and
      gingival scores was conducted using the paired sample t-test (for intragroup) and
      the Tukey's test (for intergroup conducted along with analysis of variance test).
      For the Streptococcus mutans and Lactobacillus counts, Wilcoxon and Mann-Whitney
      test were applied for intragroup and intergroup comparison, respectively. All the
      tests were carried out using the SPSS software. Both the Group I and Group II
      showed progressive decrease in plaque scores from baseline to the end of 9
      months; however, for Group III increase in plaque scores from the baseline to the
      end of 9 months was noted. Both Group I and Group II showed similar effect on
      gingival health. There was inhibitory effect on microbial counts except
      Lactobacillus where Triphala had shown better results than Chlorhexidine. It was
      concluded that there was no significant difference between the Triphala and the
      Chlorhexidine mouthwash.

PMID- 21897641
TI  - Pharmacognostical evaluation of Barringtonia acutangula leaf.
AB  - Barringtonia acutangula (L.) Gaertn. (Family: Lecythidaceae) is an evergreen tree
      with simple, alternate leaves, long pendulous racemes, dark scarlet flowers, and
      ellipsoid to ovoid berries containing one ovoid black seed. The present study
      deals with a detailed pharmacognostical study on the leaf of the crude drug, B.
      acutangula. Morphoanatomy of the leaf was studied using light and confocal
      microscopy and World Health Organization (WHO) guidelines on quality control
      methods for medicinal plant materials. Literature reveals that the
      phytoconstituents like tanginol, barrinic acid, and barringenic acid are present
      in the wood and fruits of this plant. Our preliminary phytochemical studies of
      the powdered leaves revealed the presence of terpenes, flavanoids, carbohydrates,
      tannins, steroids, and glycosides. The physico-chemical, morphological,
      histological parameters, and High Performance-Thin Layer Chromatographic (HPTLC)
      profile presented in this paper may be proposed as parameters to establish the
      authenticity of B. acutangula and can possibly help to differentiate the drug
      from its other species and the pharmacognostic profile of the leaves presented
      here will assist in standardization viz., quality, purity, and sample
      identification.

PMID- 21897642
TI  - Standardization and quality control parameters of Dashanga Kwatha ghana tablet:
      An Ayurvedic formulation.
AB  - Herbal medicines have a long therapeutic history and are still serving many of
      the health needs of a large population of the world. However, the quality control
      and quality assurance still remains a challenge because of the high variability
      of chemical components involved. Herbal drugs, singularly and in combinations,
      contain numerous compounds in complex matrices in which no single active
      constituent is responsible for the overall efficacy. This creates a challenge in
      establishing quality control standards and standardization of finished herbal
      drugs. Many preparations have been mentioned in Ayurvedic text books for the
      treatment of Urdhwaga Amlapitta (non-ulcer dyspepsia). Dashanga Kwatha is one
      such known formulation. In this study, Dashanga Kwatha was converted into tablet
      form to increase the shelf life, make it easy to dispense, for dose fixation,
      etc. The Dashanga Kwatha Ghana tablet was subjected to organoleptic analysis,
      phytochemical analysis, and qualitative analysis to detect the presence of
      various functional groups, and to high performance thin layer chromatography
      (HPTLC) examination by optimizing the solvent systems. The investigation revealed
      the presence of tannins, mucilage, ascorbic acid, alkaloids, saponins,
      glycosides, flavonoids and carbohydrates mainly.

PMID- 21897643
TI  - Why and how? Addressing to the two most pertinent questions about
      pharmacovigilance in Ayurveda.
AB  - Pharmacovigilance is the outcome of a natural and implied willingness of a
      physician to ensure safety to his patient. This is a discipline in medicine which
      pragmatises the principle of first do no harm towards a wider and systematic
      application in clinical practice. It is however important to understand that
      despite of its huge potential in ensuring a safe practice of medicine through
      knowledge of avoidable causes of adversities, its path has never been easy.
      Applying principles of pharmacovigilance into the realm of traditional medicine
      particularly to Ayurveda is even more difficult for the issues of why and how of
      pharmacovigilance in light of historical practice and anecdotal evidences of
      safety in Ayurveda. Application of pharmacovigilance in Ayurveda thereby demands
      a careful and thoughtful observation of its needs and its methods of application
      in order to to maximize its impacts to ensure the patient safety to every extent
      possible.

PMID- 21897644
TI  - Shushkakshipaka (dry eye syndrome): A case study.
AB  - Ashru-tear secretion is an integral component of the ocular surface physiology;
      when compromised (quantitatively or qualitatively) lead to shushkakshipaka (dry
      eye syndrome) with various ocular discomfort symptoms and ultimately the patient
      may land in corneal blindness.Local, systemic and environmental factors play a
      major role in its pathogenisis. Vata& Pitta/Rakta vitiation as per Ayurvedic view
      point are the major contributing pathological factors in its manifestation.
      Contrary to the available modern medical treatment / management regimen; Ayurveda
      propounds a systematic systemic/ holistic treatment approach in the treatment of
      dry eye syndrome. A patient of shushkakshipaka was treated with such treatment
      protocol, is presented as a case study in this article.

PMID- 21897645
TI  - Treatment of relapsed undifferentiated acute myeloid leukemia (AML-M0) with
      Ayurvedic therapy.
AB  - A 16-year-old boy was detected with acute myeloid leukemia (AML - M0) with bone
      marrow pathology showing 85% blasts in February 07, 1997. He received two cycles
      of induction chemotherapy (3+7 protocol) with daunomycin and cytosar, following
      which he achieved incomplete remission with bone marrow aspirate showing 14%
      blasts. Subsequently, the patient received two cycles of high-dose cytosine
      arabinoside Ara-C and achieved remission. However, his disease relapsed on August
      29, 1997. Peripheral blood smear showed 6% blast cells and bone marrow showed 40%
      blast cells. The patient refused further chemotherapy and/or bone marrow
      transplant and volunteered for Ayurvedic therapy (AYT) advocated by the author
      from September 09, 1997. Bone marrow studies done after six months of AYT
      indicated that the disease was in remission. The AYT was continued for five years
      and stopped. Thereafter, the patient received intermittent maintenance AYT for
      three months in the next two years. At present, the patient is normal and healthy
      and has completed 12 years of disease-free survival with AYT.

PMID- 21897646
TI  - Seminal gold and infertility.

PMID- 21897647
TI  - Effect of insulin plant leaves on dexamethasone-induced hyperglycemia.

PMID- 21897648
TI  - Authors' reply.

PMID- 21897649
TI  - Revisiting survival analysis.

PMID- 21897650
TI  - Effect of Tulsi (Ocimum sanctum Linn) on sperm count and reproductive hormones in
      male albino rabbits.

PMID- 21897651
TI  - A survey of the labeling information provided for Ayurvedic drugs marketed in
      India.

PMID- 21897652
TI  - Authors' reply.

PMID- 21897653
TI  - Ayurveda support for health prevention in post crisis, nuclear denotation.

PMID- 21897654
TI  - Design of vitamin E d-alpha-Tocopheryl Polyethylene Glycol 1000 Succinate
      Emulsified Poly (D,L-Lactide-co-Glycolide) Nanoparticles: Influence of Duration
      of Ultrasonication Energy.
AB  - The aim of this research was to investigate the effect of the duration of
      ultrasonication energy on the physicochemical characteristics of the nano-sized
      particulate drug delivery systems. For this purpose, meloxicam-loaded vitamin E d
      alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS)-emulsified poly (D,L
      lactide-co-glycolide) (PLGA) nanoparticles were designed by using ultrasonication
      solvent evaporation technique and were characterized by photon correlation
      spectroscopy for size and size distribution, scanning electron microscopy for
      surface morphology and laser Doppler anemometry for surface charge. Ultraviolet 
      spectrophotometer was used to measure the drug encapsulation efficiency and to
      obtain in vitro drug release profile. The results showed that the physicochemical
      properties of the prepared nanoparticles are effectively controlled by the amount
      of shear stress transferred from the energy source to the emulsion, which is
      strongly correlated to the ultrasonication time.

PMID- 21897655
TI  - Design of Controlled Release Non-erodible Polymeric Matrix Tablet Using Microwave
      Oven-assisted Sintering Technique.
AB  - The objective of the present study was to evaluate the effect of sintering
      condition on matrix formation and subsequent drug release from polymer matrix
      tablet for controlled release. The present study highlights the use of a
      microwave oven for the sintering process in order to achieve more uniform heat
      distribution with reduction in time required for sintering. We could achieve
      effective sintering within 8 min which is very less compared to conventional hot
      air oven sintering. The tablets containing the drug (propranolol hydrochloride)
      and sintering polymer (eudragit S-100) were prepared and kept in a microwave oven
      at 540 watt, 720 watt and 900 watt power for different time periods for
      sintering. The sintered tablets were evaluated for various tablet characteristics
      including dissolution study. Tablets sintered at 900 watt power for 8 min gave
      better dissolution profile compared to others. We conclude that microwave oven
      sintering is better than conventional hot air oven sintering process in
      preparation of controlled release tablets.

PMID- 21897656
TI  - Dissofilm: a novel approach for delivery of phenobarbital; design and
      characterization.
AB  - An attempt to develop and evaluate mouth-dissolving film of phenobarbital for
      quick effect in treatment of epilepsy occurring in pediatric population has been
      made in the present study. Suitable film formers and plasticizers are selected
      based on optimization studies. Effect of superdisintegrants in formulation of
      mouth dissolving films at different concentrations has been investigated. Films
      were prepared by solvent casting method. The prepared films were evaluated for
      physicochemical parameters, in vitro disintegration and dissolution time, in
      vitro release rate study, stability study, and in vivo animal safety study. The
      best formulation was found to be F3 showing 96.57% drug release in 14 min,
      following first-order kinetics. X-Ray diffraction studies show change in
      crystalline nature of drug in formulation. In vivo studies in hamster reports
      effective and safe use of formulation in animals.

PMID- 21897657
TI  - Preparation and evaluation of mixture of eudragit and ethylcellulose
      microparticles loaded with ranolazine for controlled release.
AB  - To minimize the unwanted toxic effects of anti-anginal ranolazine by kinetic
      control of drug release, it was entrapped into gastro-resistant, biodegradable
      eudragit (EU) and ethyl cellulose (EC) binary blend using phase separation
      method. Ten formulations were prepared using different polymer blend ratios and
      solvent. The prepared microparticles were characterized for micromeritic
      properties, polymer drug compatibility by Fourier Transform Infrared Spectroscopy
      (FT-IR) and Differential Scannibg Calorimetry (DSC), and surface morphology by
      Scanning Electron Micrography (SEM). The yield of microparticles was up to 90%
      and more than 98% of the isolated microparticles are having volume mean diameter
      of 285 MUm. The obtained angle of repose, percentage Carr's index and tapped
      density values were within the limits indicating good flow properties. The
      surface morphology revealed that particles were free-flowing, spherical, with
      minute pores and invert dents on the surface. The prepared microparticles were
      evaluated for percentage yield, encapsulation efficiency and in vitro release
      studies. FT-IR and DSC studies showed no chemical interaction between the drug
      and used polymers The in vitro drug release studies were carried out using pH 1.2
      acid buffer and pH 7.4 phosphate buffer. EU acts as an excellent pH-dependent
      binder and helps to release the drug in the intestine. The drug release kinetics
      followed different transport mechanisms. Increasing the weight fractions of EU
      and decreased EC helps to control the drug release from the particles. From the
      differential (f(1)) and similarity factor (f(2)), Formulation F5 was the
      formulation most similar to the commercially available oral formulation as
      reference standard. The drug release performance was greatly affected by the
      materials used in microparticle preparations, which allow absorption in the
      intestinal tract.

PMID- 21897658
TI  - Preparation and Characterization of Metformin Hydrochloride - Compritol 888 ATO
      Solid Dispersion.
AB  - Metformin hydrochloride (MET) sustained-release solid dispersions (SD) were
      prepared by the solvent evaporation and closed melt method, using compritol 888
      ATO as the polymer with five different drug-carrier ratios. Characterization of
      solid dispersion was carried out by Fourier Transform Infrared (FTIR)
      spectroscopy, ultraviolet (UV) spectroscopy, Differential scanning calorimetry
      (DSC), X-ray powder diffraction (XRPD). The FTIR and UV studies suggested that no
      bond formation had occurred between the polymer and the drug. DSC and XPRD
      results ruled out any interaction or complex formation between the drug and the
      polymer. The formulated SD had acceptable physicochemical characters and SD with
      a 1 : 4 drug : Polymer ratio, which released the drug over an extended period of
      eight-to-ten hours. The data obtained from the in vitro release studies were
      fitted with various kinetic models and were found to follow the Korsmeyer-Peppas
      equation. The prepared SD showed good stability over the studied time period. The
      solvent evaporation method was found to be more helpful than the closed melt
      method, giving the sustained release action. The SD with a 1 : 4 ratio of drug to
      polymer, by the solvent evaporation method, was selected as the most effective
      candidate for the subsequent development of a well-timed, sustained-release
      dosage form of the drug.

PMID- 21897659
TI  - Preparation and Evaluation of Silymarin beta-cyclodextrin Molecular Inclusion
      Complexes.
AB  - Silymarin is a hepatoprotective agent, having poor water solubility and oral
      absorption of about 23 - 47%, leading to low bioavailability of the drug. The aim
      of the present study is to improve the solubility and dissolution rate and in
      turn the hepatoprotective activity of the drug, by formulating its inclusion
      complex with beta (beta)-cyclodextrin, using different methods. The phase
      solubility analysis indicates the formation of 1:1 molar inclusion complex of the
      drug with beta cyclodextrin. Apparent stability constant for Silymarin (K(c)) was
      722 K(-1) with beta-cyclodextrin complex. The inclusion complexes were prepared
      by four different methods, namely, physical mixing, kneading, co-precipitation,
      and solvent evaporation. The prepared complexes were characterized using
      differential scanning colorimetry, scanning electron microscopy, and x-ray
      diffractometry. The inclusion complex prepared by the co-precipitation methods
      exhibits an overall best result, with respect to the formulation of sustained
      release formulations.

PMID- 21897660
TI  - Hordeum vulgare hull in the design of fast disintegrating tablets.
AB  - In the present study, fast disintegrating tablets were designed with a view to
      enhance patient compliance. In this method, the hull of Hordeum vulgare, cross
      carmellose sodium, and sodium starch glycolate were used as superdisintegrants (4
      and 6%), along with microcrystalline cellulose and mannitol, to enhance mouth
      feel. The prepared batches of tablets were evaluated for hardness, friability,
      drug content uniformity, wetting time, water absorption ratio and in vitro
      dispersion time. Based on the in vitro dispersion time, the formulations were
      tested for the in vitro drug release pattern. Tablets having H. vulgare hull
      showed the release profile comparable to those tablets having sodium starch
      glycolate and cross carmellose sodium.

PMID- 21897661
TI  - Formulation and evaluation of solid lipid nanoparticles of ramipril.
AB  - Solid lipid nanoparticles are typically spherical with an average diameter
      between 1 and 1000 nm. It is an alternative carrier system to tradition colloidal
      carriers, such as, emulsions, liposomes, and polymeric micro and nanoparticles.
      Ramipril is an antihypertensive agent used in the treatment of hypertension. Its
      oral bioavailability is 28% and it is rapidly excreted through the renal route.
      This drug has many side effects such as, postural hypotension, hyperkalemia, and
      angioedema, when given as an immediate dosage form. To overcome the side effects
      and to increase the bioavailability of ramipril, solid lipid nanoparticles of
      ramipril are prepared by using lipids (glyceryl monostearate and glyceryl
      monooleate) with stabilizers (tween 80, poloxamer 188, and span 20). The prepared
      formulations have been evaluated for entrapment efficiency, drug content, in
      vitro drug release, particle size analysis, scanning electron spectroscopy,
      Fourier transform-infrared studies, and stability. A formulation containing
      glyceryl monooleate, stabilized with span 20 as surfactant showed prolonged drug
      release, smaller particle size, and narrow particle size distribution, as
      compared to other formulations with different surfactants and lipids.

PMID- 21897662
TI  - Pharmacognostic standardization, physico- and phytochemical evaluation of
      amaranthus spinosus linn. Root.
AB  - Amaranthus spinosus Linn. (Amaranthaceae) is found throughout India. This tree
      species has been of interest to researchers because it is a medicinal plant
      employed in the Indian traditional system of medicine. Pharmacognostic
      standardization; physico-and phytochemical evaluation of the roots of Amaranthus
      spinosus was carried out, to determine its macro-and microscopical characters,
      and also some of its quantitative standards. Microscopical studies were done by
      using the trinocular microscope. Total ash, water-soluble ash, acid-insoluble
      ash, sulfated ash values, and alcohol-and water-soluble extractive values were
      determined for physico-chemical evaluations. A preliminary phytochemical
      screening was also done to detect different phytoconstituents. Microscopically,
      the root showed cork, cortex, stellar region, and calcium oxalate crystals.
      Powder microscopy showed anamalous secondary growth in between the xylem vessels
      and Calcium Oxalate crystals in the cortex region. Total ash was approximately
      three times more than acid insoluble and water soluble ash. The ethanol soluble
      extractive was approximately the same as the water soluble extractive. Thin Layer
      Chromatography (TLC) of the Petroleum-ether extract using Benzene : Ethyl acetate
      (6 : 1), showed six spots. In the chloroform extract, using Benzene : Ethyl
      acetate (4 : 1) nine spots were seen, and in the ethanol extract, using
      Chloroform: Methanol (93 : 7), only four spots were observed, using Iodine vapor
      as a viewing medium. Phytochemically, the root exhibited terpenes, alkaloids,
      glycosides, and sugars. These findings might be useful to supplement information
      with regard to its identification parameters, which are assumed significant in
      the way of acceptability of herbal drugs, in the present scenario, which lacks
      regulatory laws to control the quality of herbal drugs.

PMID- 21897663
TI  - Sepbox technique in natural products.
AB  - Natural compounds still play an increasingly important role in many areas of
      research and development. Their structural diversity is enhanced by the synthetic
      potential of combinatorial chemistry. Fractionation and separation of samples
      obtained from nature remain time-consuming, tedious and extremely expensive even
      though the assays for testing these samples have become faster and more cost
      effective thanks to advanced high-throughput screening (HTS) processes. Today,
      sepbox is the standard technology used for separating compounds from natural
      resources. Fractionations and separation of samples obtained from nature remain
      very difficult. Automation of sample preparation therefore has great economic
      potential. The unique sepbox concept allows processing sample automatically and
      will make up to 30 times faster than by using a conventional process.

PMID- 21897664
TI  - Central Nervous System Effects of Iso-6-spectaline Isolated from Senna
      Spectabilis var. Excelsa (Schrad) in Mice.
AB  - The central nervous system (CNS) depressant and anticonvulsant activities of iso
      6-spectaline (SPEC) were investigated in animal models. The SPEC from Senna
      spectabilis var. excelsa (Schrad) (0.1, 0.5 and 1.0 mg/ kg) injected by oral
      route (p.o.) in mice caused a significant decrease in the motor activity up to 30
      days after the administration and in the dose of 1.0 mg/kg significantly reduced
      the remaining time on the Rota-rod apparatus. Additionally, SPEC (0.1, 0.5 and
      1.0 mg/kg, p.o.) was also capable of promoting increase of latency for
      development of convulsions induced by pentylenetetrazole. This SPEC was also
      capable of promoting an increase of latency for development of convulsions
      induced by picrotoxin at highest dose. In the same way, the anticonvulsant effect
      of SPEC was affected by pretreatment with flumazenil, a selective antagonist of
      the benzodiazepine site of the GABA(A) receptor. These results suggest possible
      CNS depressant and anticonvulsant activities in mice that needs further
      investigation.

PMID- 21897665
TI  - Aqueous Methanol Extracts of Cochlospermum tinctorium (A. Rich) Possess Analgesic
      and Anti-inflammatory Activities.
AB  - Cochlopermum tinctorium A. Rich. (Cochlospermaceae) is a commonly used medicinal
      plant in the West Africa sub-region for the management of various conditions
      including pain and inflammatory conditions. In the present study, we report the
      analgesic and anti-inflammatory activities of the aqueous methanol leaf (20-80
      mg/kg), root (7.5-30 mg/kg), and root bark (20-80 mg/kg) extracts of the plant.
      The analgesic potentials of the extracts were studied using acetic acid induced
      writhing and hot plate tests in mice while the anti-inflammatory activity was
      investigated using carrageenan-induced paw edema in rats.The extracts
      significantly and dose dependently inhibited the acetic acid-induced writhing in
      mice. However, the highest protection against writhing was produced by aqueous
      methanol leaf extract at the dose of 80 mg/kg (96.65%) which even was greater
      than that of the standard agent, ketoprofen (82.30%). The extracts did not
      significantly increase mean latency of response in the hot plate test. However,
      aqueous methanol root bark extract at the dose of 20 mg/kg significantly (P <
      0.05) increased the mean latency of pain response. While the extracts of the root
      and root bark extracts of the plant afforded non dose-dependent protection
      against carrageenan-induced edema, the aqueous methanol leaf extract
      significantly and dose-dependently inhibited carrageenan-induced hind paw edema
      at the end of the third hour.The present study suggests that the aqueous methanol
      leaf, root, and root bark extracts of Cochlopermum tinctorium possess analgesic
      and anti-inflammatory activities which lend some credence to the ethnomedical
      claim of the use of the plant in the management of pain and inflammatory
      conditions.

PMID- 21897666
TI  - Studies on the anthelmintic property of aminobenzylated mannich bases.
AB  - Studies were conducted on the anthelmintic property of about 15(e-h, 1e-1h, 2d-2f
      and 3e-3h) synthesized aminobenzylated Mannich bases bearing N-methyl piperazine
      using Indian earthworms Pheritima Posthuma against piperazine citrate as standard
      reference. Three concentrations of each compound (0.1, 0.2, 0.3% w/v) were
      studied, which involved the determination of paralysis and death time of the
      worms. The compound 1g exhibited the most significant anthelmintic activity among
      all the compounds screened against the worms as compared to standard drug.

PMID- 21897667
TI  - In-silico Comparative Study and Quantitative Structure-activity Relationship
      Analysis of Some Structural and Physiochemical Descriptors of Elvitegravir
      Analogs.
AB  - Elvitegravir is a new-generation drug which acts as an integrase inhibitor of the
      HIV virus. The potential inhibition has been tested from the clinical trial data.
      Here the work basically deals with the quantitative structure-activity
      relationship (QSAR) analysis by considering some of the physiochemical
      descriptors like molecular weight, logP, molar volume, and structural descriptors
      like Winers index, and molecular topological index of the drug analogs. The
      descriptors were calculated from the E-Dragon server and the multiple linear
      regression equation models were built by using Minitab tools. The different
      combinations of structural and physiochemical descriptors were considered for
      model derivation. The best three models were chosen by observing high R-Sq value,
      high F-value and low residual errors. The P values (regression) for the three
      models indicates the significance of the considered descriptors.The overall
      results obtained with these model suggest that for this perticular drug the
      activity is dependent on physiochemical descriptors.

PMID- 21897668
TI  - Patient-physician Communication Barrier: A Pilot Study Evaluating Patient
      Experiences.
AB  - This study aims to identify the patient-physician communication barriers in the
      primary healthcare setting in Pulau Penang, Malaysia. A cross-sectional study was
      designed to attain the objectives of the study. A self-developed 17-item study
      tool was used to explore respondent's perception about the barriers they have
      faced while communicating with physician. The reliability scale was applied and
      internal consistency of the study tool was estimated on the basis of Cronbach's
      alpha (alpha = 0.58). The data analysis was conducted using statistical package
      for social sciences students SPSS 13((r)). Chi Square test was used to test the
      difference between proportions. A total of n = 69 patients responded to this
      survey. A higher participation was seen by the male respondents, 39 (56.5%).
      About 52 (76.5%) of the respondents were satisfied with the information provided
      by the physician. In an effort to identify the patient-physician barriers, a poor
      understanding among the patients and physician was revealed. 16 (23.5%)
      respondents disclosed lack of satisfaction from the information provided to them.
      Overall, it is seen that lack of physician-patient understanding was the main
      reason that result hindrance in the affective communication. Moreover, there is a
      possibility that a low level of health literacy among the patients and inability
      of the physician to affectively listen to patients may be the other factors that
      result in a deficient communication.

PMID- 21897669
TI  - Pharmacovigilance of herbal products in India.
AB  - Herbal formulations being widely accepted therapeutic agents as antidiabetics,
      antiarthritics, hepatoprotectives, cough remedies, memory enhancers, and
      adaptogens. The commonest myth regarding herbal medicines is that these medicines
      are completely safe, and can therefore be safely consumed by the patient on
      his/her own, without a physician's prescription. This belief has led to large
      scale self-medication by people all over the world, often leading to
      disappointing end-results, side-effects, or unwanted after-effects. There is an
      increasing awareness at several levels of the need to develop pharmacovigilance
      practices for herbal medicines. The current model of pharmacovigilance and its
      associated tools have been developed in relation to synthetic drugs, and applying
      these methods to monitoring the safety of herbal medicines presents unique
      challenges in addition to those described for conventional medicines. Several
      problems relate to the ways in which herbal medicines are named, perceived,
      sourced, and utilized. This may be because of differences in the use of
      nonorthodox drugs (e.g., herbal remedies) which may pose special toxicological
      problems, when used alone or in combination with other drugs. The purpose of
      pharmacovigilance is to detect, assess, and understand, and to prevent the
      adverse effects or any other possible drug-related problems, related to herbal,
      traditional, and complementary medicines.

PMID- 21897670
TI  - Of water bags and wind pipes: The travails of securing airway in occipital
      encephalocoele.

PMID- 21897671
TI  - Utilization patterns of central nervous system drugs: A cross-sectional study
      among the critically ill patients.
AB  - INTRODUCTION: Critically ill patients often receive central nervous system drugs
      due to primary disorder or complications secondary to multiorgan failure. The aim
      of the study was to evaluate the current utilization pattern of central nervous
      system drugs among patients in the medical intensive care unit. MATERIALS AND
      METHODS: A prospective observational study carried out over a period of 1 year.
      The relevant data on drug prescription of each patient was collected from the
      inpatient case record. Drugs were classified into different groups based on WHO
      ATC classification. The demographic data, clinical data, and utilization of
      different classes of drugs as well as individual drugs were analyzed. RESULTS: A
      total of 325 consecutive patients were included for the analysis; 211 (65%)
      patients were males; 146 patients (45%) were above 55 years of age.
      Encephalopathy [63(19.38%)] and stroke [62(19%)] were the common central nervous
      system diagnoses. In a total of 1237 drugs, 68% of the drugs were prescribed by
      trade name. Midazolam (N05CD08) 142 (43.69%), morphine (N02AA01) 201 (61.84%),
      and atracurium (M03AC04) 82 (25.23%) were the most commonly used sedative,
      analgesic, and neuromuscular blocker, respectively. Phenytoin (N03AB02) 151
      (46.46%) had maximum representation among antiepileptic agents. CONCLUSIONS:
      Utilization of drugs from multiple central nervous system drug classes was
      noticed. Rational use of drugs can be encouraged by prescription by brand name.

PMID- 21897672
TI  - Commentary.

PMID- 21897673
TI  - Immunoreactivity of glycoproteins isolated from human peripheral nerve and
      Campylobacter jejuni (O:19).
AB  - OBJECTIVE: Antibodies to ganglioside GM1 are associated with Guillain-Barre
      Syndrome (GBS) in patients with serologic evidence of a preceding infection with
      Campylobacter jejuni. Molecular mimicry between C. jejuni Lipopolysaccharide
      (LPS) and ganglioside GM1 has been proven to be the immunopathogenic mechanism of
      the disease in the axonal variant of GBS. GM1-positive sera cross-react with
      several Gal-GalNAc-bearing glycoproteins from the human peripheral nerve and C.
      jejuni (O:19). This study aimed to examine the immunoreactivity of the digested
      cross-reactive glycoproteins isolated from the human peripheral nerve and C.
      jejuni (O:19) with Peanut Agglutinin (PNA) as a marker for the Gal-GalNAc
      determinant, and with sera from patients with GBS. MATERIALS AND METHODS: For
      this purpose, the cross-reactive glycoproteins from peripheral nerve and C.
      jejuni (O:19) were enzymatically digested with trypsin and the obtained peptides
      were incubated with PNA and GBS sera. RESULTS: Western blot analysis of the
      separated peptides revealed several bands showing positive reactivity to PNA and
      to sera from patients with GBS, present in both digests from peripheral nerve and
      C. jejuni (O:19). CONCLUSIONS: These data indicate the possible molecular mimicry
      between the cross-reactive glycoproteins present in C. jejuni and human
      peripheral nerve and its potential role in the development of GBS following
      infection with C. jejuni (O:19).

PMID- 21897674
TI  - Comparison of antinociceptive effect of the antiepileptic drug gabapentin to that
      of various dosage combinations of gabapentin with lamotrigine and topiramate in
      mice and rats.
AB  - INTRODUCTION: Newer anticonvulsants have a neuromodulatory effect on pain
      perception mechanisms in a hyperexcitable and damaged nervous system. AIM: This
      study was designed to study the analgesic effects of gabapentin alone and in
      combination with lamotrigine and topiramate in experimental pain models.
      MATERIALS AND METHODS: Adult albino mice (n=490) weighing 20-30 g and rats
      (n=130) weighing 100-200 g were injected intraperitoneally with gabapentin,
      lamotrigine, and topiramate alone and in different dose combinations. The hot
      plate method, tail-flick method, capsaicin-induced mechanical hyperalgesia, and
      formalin assay were used to assess the antinociceptive effects. RESULTS: Of the
      three antiepileptic drugs, when given separately, gabapentin was more efficacious
      than either topiramate or lamotrigine in all the pain models. Combination of 25
      mg/kg gabapentin with 25 mg/kg topiramate was more efficacious (P<.05) than 50
      mg/kg gabapentin alone in the capsaicin-induced mechanical hyperalgesia test.
      Similarly, 50 mg/kg gabapentin with 50 mg/kg topiramate or 5 mg/kg lamotrigine
      was more efficacious (P<.05) than 50 or 100 mg/kg gabapentin alone in late-phase
      formalin-induced behaviors. CONCLUSIONS: Combination of gabapentin with either
      lamotrigine or topiramate produced better results than gabapentin alone in
      capsaicin-induced mechanical hyperalgesia test and in late-phase formalin-induced
      behaviors.

PMID- 21897675
TI  - Anesthetic and surgical predictors of treatment outcome in re-do craniotomy.
AB  - INTRODUCTION: Craniotomy is a neurosurgical operation done to remove brain tumor,
      repair vascular lesion, and relieve intracranial pressure. Complications can
      arise which may necessitate re-do craniotomy. The study is planned to find out
      the relationship between variables such as age, American Society of
      Anaesthesiologist (ASA), Glasgow coma score (GCS), frequency of re-do craniotomy,
      and surgical outcome of re-do craniotomy. MATERIALS AND METHODS: This is a
      retrospective study of all the patients who had re-do craniotomy over a 4-year
      period. The data that were collected included age, sex, ASA classification,
      indication for re-do craniotomy, GCS, frequency of re-do craniotomy,
      postoperative complications, and outcome. RESULTS: Twenty-five patients had
      indication for re-do craniotomy within the study period. Forty percent were male
      and 60% were female, and their mean age was 38.56 +/- 17.38 years. The
      indications for re-do craniotomy were removal of residual tumor, evacuation of
      clot, and cerebrospinal fluid leakage. Seventy-six percent had good outcome,
      while 24% had poor outcome. Outcome was good for patients who had re-do
      craniotomy done once, while poor outcome was for patients with second and third
      craniotomies. Ninety percent of patients with ASA (2) had good outcome, while
      9.1% had poor outcome; but 64.3% had good outcome with ASA (3), while 37.7% had
      poor outcome with a P-value of 0.18. Seventy-five percent had poor outcome in
      patients with GCS of less than 9, while 25% had good outcome; but 14.3% had poor
      outcome in patients with GCS above 9, while 85.7% had good outcome with a P-value
      of 0.031. CONCLUSIONS: Increasing frequency of re-do craniotomy and lower GCS
      were major factors affecting outcome in re-do craniotomy in our center. The
      outcome of these patients is valuable in the management of other patients with re
      do craniotomy in future.

PMID- 21897676
TI  - Inpatient occupational therapists hand-splinting practice for clients with
      stroke: A cross-sectional survey from Ireland.
AB  - INTRODUCTION: Hand splinting after stroke is a common practice despite inadequate
      evidence. This warrants a better understanding of the therapists' splinting
      practice, to develop clinically meaningful treatment options. AIMS: The study
      examined the nature and prevalence of the factors associated with therapists'
      hand splinting practice and their perceived splinting efficacy. SETTINGS AND
      DESIGN: A cross-sectional national survey of hand-splinting practice among
      inpatient occupational therapists (OTs) in Ireland. MATERIALS AND METHODS: Sixty
      two therapists participated in this national survey. STATISTICAL ANALYSIS USED: A
      number of factors were analyzed to explore their relationship with therapists'
      perception of splint efficacy using Spearman's rank order correlation. RESULTS:
      53(85.5%) out of 62 survey respondents prescribed splints to their clients at the
      time of taking the survey. To reduce spasticity, to correct contractures and thus
      increase range of motion (ROM) were the commonly used splinting goals. These were
      the goals that were significantly associated with the therapists' splinting
      efficacy too. CONCLUSIONS: Hand-splint prescription following stroke was found to
      be a common practice among OTs who perceive splints to be quite effective. A
      custom-made, volar forearm-based wrist-hand splint is the preferred splint among
      therapists to achieve a number of clinical aims such as improving ROM, stretching
      soft tissue contractures and reducing spasticity in the upper extremity. A wide
      variety of splinting regimens is currently practiced, reflecting the lack of a
      universally accepted and comprehensive practice guideline to regulate therapy.
      Methodologically valid clinical trials evaluating the efficacy of therapist
      preferred splints in achieving their favored outcomes are needed. Development of
      common, universally accepted therapeutic guidelines based on comprehensive
      scientific review of such studies is thus needed.

PMID- 21897677
TI  - Role of transcutaneous electric nerve stimulation in the management of trigeminal
      neuralgia.
AB  - BACKGROUND: Trigeminal neuralgia typically involves nerves supplying teeth, jaws
      and face of older females. Though the etiology is usually obscure, different
      treatment modalities have been tried for it viz. medicinal treatment, injection
      alcohol, peripheral neurectomy, rhizotomy, and microvascular decompression etc.
      Transcutaneous electric nerve stimulation (TENS) is an emerging and promising
      option for management of such patients. AIMS AND DESIGN: The present study was
      designed with an aim to study the efficacy of TENS in management of trigeminal
      neuralgia. MATERIALS AND METHODS: The study was conducted on 30 patients of
      trigeminal neuralgia confirmed by diagnostic nerve block. They were given bursts
      of TENS for 20-40 days over the path of the affected nerve and subsequently
      evaluated at 1 month and 3 month intervals by visual analogue scale (VAS), verbal
      pain scale (VPS), a functional outcome scales for main daily activities like
      sleep, chewing, talking, or washing face. RESULTS: The results showed that, on
      VAS, the score decreased from 8.9 (Pre TENS) to 3.1 at 1 month and 1.3 at 3
      months, and on VPS, the score decreased from 3.5 (Pre TENS) to 1.2 at 1 month and
      0.3 at 3 months. Similarly, a considerable decrease in scores was seen on
      functional outcome scale for different activities. No side effects like
      irritation or redness of skin were seen in any of the patients. CONCLUSIONS:
      Thus, TENS was found to be a safe, easily acceptable, and non-invasive outdoor
      patient department procedure for management of trigeminal neuralgia.

PMID- 21897678
TI  - Tuberculous brain abscesses: Case series and review of literature.
AB  - INTRODUCTION: Tuberculous brain abscess (TBA) is a rare but serious condition. It
      resembles a pyogenic brain abscess clinically and radiologically and poses a
      problem in diagnosis and treatment. A final diagnosis is established by smear or
      culture demonstration of acid fast bacilli (AFB) within the abscess. Here, we
      report four such cases in our five-year study on brain abscesses, along with the
      different diagnostic modalities used. MATERIALS AND METHODS: A total of 75 brain
      abscess pus specimens were collected during neurosurgery, either by burr hole or
      by craniotomy. These specimens were further subjected to Gram stain, Ziehl
      Neelsen (ZN) stain, and conventional microbiological culture. Only those cases
      which showed presence of AFB on ZN stain along with the growth of Mycobacterium
      tuberculosis were considered as TBAs. Such TBA cases were further presented along
      with their In vitro Proton Magnetic Resonance (MR) Spectroscopic findings.
      RESULTS: Of these four patients, three were males. Though this condition is more
      commonly seen in immunocompromised patients, three of the patients in this study
      were immunocompetent. All the four pus specimens showed presence of AFB in the ZN
      stain. Three of them grew M. tuberculosis as sole isolate. The fourth case was of
      concomitant tuberculous and pyogenic brain abscess. In vitro Proton MR
      spectroscopy of the pus specimens showed absence of multiple amino acids at 0.9
      ppm, which was found to be hallmark of TBA. One patient died of four.
      CONCLUSIONS: TBA always poses a diagnostic dilemma. ZN stain and conventional
      microbiological culture for Mycobacteria always help to solve this dilemma. In
      vitro Proton MR Spectroscopy also seems to have the diagnostic utility.

PMID- 21897679
TI  - Commentary.

PMID- 21897680
TI  - Airway management for occipital encephalocele in neonatal patients: A review of
      17 cases.
AB  - INTRODUCTION: Encephalocele, midline defect of cranial bone fusion, occurs most
      frequently in the occipital region. Airway management in pediatric patients with
      craniofacial disorders poses many challenges to the anesthesiologist. The purpose
      of this study is to describe the airway problems encountered for such cases, and
      describe how these problems were managed. MATERIALS AND METHODS: We reviewed the
      charts of occipital encephalocele newborn that were treated by surgical
      correction in Harran University Hospital during 2006-2008. The collected data
      were categorized into preoperative, intraoperative, and postoperative data.
      RESULTS: The mean age of the patients was 5.17 days. Of these 17 patients, eight
      patients (47.1%) had hydrocephaly, one patient (5.8%) with Dandy Walker syndrome.
      Micrognathia, macroglossia, restriction in neck movements were recorded as the
      reasons in six cases each. No major anesthetic complication was found.
      CONCLUSIONS: We reported perioperative management in 17 occipital encephalocele
      infant. Comprehensive care during peroperative period is essential for successful
      outcome.

PMID- 21897681
TI  - Cranioplasty: Review of materials and techniques.
AB  - Cranioplasty is the surgical intervention to repair cranial defects. The aim of
      cranioplasty is not only a cosmetic issue; also, the repair of cranial defects
      gives relief to psychological drawbacks and increases the social performances.
      Many different types of materials were used throughout the history of
      cranioplasty. With the evolving biomedical technology, new materials are
      available to be used by the surgeons. Although many different materials and
      techniques had been described, there is still no consensus about the best
      material, and ongoing researches on both biologic and nonbiologic substitutions
      continue aiming to develop the ideal reconstruction materials. In this article,
      the principle materials and techniques of cranioplasty are reviewed.

PMID- 21897682
TI  - Treatment-related fluctuation in Guillain-Barre syndrome.
AB  - Guillain-Barre syndrome (GBS) is usually a monophasic illness but relapses occur.
      A 55-year-old female with hypertension and vitiligo presented with acute
      inflammatory demyelinating polyradiculoneuropathy. She improved with
      immunoglobulin treatment started on day 6 of illness, but relapsed on day 14
      warranting repeat immunoglobulin therapy. Thereafter recovery was complete. Her
      relapse was due to treatment-related fluctuation (TRF). TRF is improvement in the
      GBS disability scale of at least one grade after completion of immunotherapy
      followed by worsening of the disability scale of at least one grade within the
      first 2 months after disease onset. Recurrent GBS and chronic inflammatory
      demyelinating polyradiculoneuropathy were excluded. During the peak of the
      illness ANA titres were transiently high. The presence of other medical
      conditions, predominant proximal weakness and the absence of preceding diarrhea
      are predictors for TRF seen in this patient. Early treatment and evidence of
      ongoing immune activation have contributed toward TRF.

PMID- 21897683
TI  - Unusual features in chronic inflammatory demyelinating polyneuropathy: Good
      outcome after prolonged ventilatory support.
AB  - Severe respiratory muscle paralysis and ventilatory failure is rare in chronic
      inflammatory demyelinating polyneuropathy (CIDP). We report a 14 year child who
      presented with respiratory failure, bulbar and multiple cranial nerves
      involvement along with bilateral phrenic nerve paralysis. He was diagnosed with
      CIDP after electrophysiological evaluation. He required AMBU ventilation for
      about 4 months (including domiciliary use), after which he recovered
      significantly. Along with several unusual features of CIDP, this report
      highlights good example of steady basic intensive care to save lives and
      rewarding outcome of prolonged respiratory support, provided by AMBU ventilation
      which is a rather primitive, but inexpensive device.

PMID- 21897684
TI  - Giant primary ossified cavernous hemangioma of the skull in an adult: A rare
      calvarial tumor.
AB  - Primary intraosseous cavernous hemangiomas (PICHs) of the cranium are rare benign
      vascular tumors that account for about 0.2 % of all bone tumors and 10 % of
      benign skull tumors. They generally present as osteolytic lesions with honeycomb
      pattern of calcification. Completely ossified cavernous hemangioma of the
      calvarium in an adult has not been reported previously. A 28-year-old female
      presented to us with a large right parietal skull mass that had been present
      since the last 15 years. Total resection of the lesion was performed.
      Pathological examination was suggestive of cavernous hemangioma of the skull
      bone. Cavernous hemangioma should be considered as one of the differential
      diagnosis in any case of bony swelling of the calvarium so that adequate
      preoperative planning can be made to minimize blood loss and subsequent
      morbidity.

PMID- 21897685
TI  - Occipital artery occlusion to facilitate transmastoid posterior fossa tumor
      embolization.
AB  - The transmastoid branch of the occipital artery is an important supply to
      posterior fossa vascular malformations and tumors and is often difficult to
      catheterize due to tortuosity and a transforaminal course. In very difficult
      situations, we can try to induce spasm of the occipital artery just beyond the
      origin of the mastoid branch by repeated passages of the microcatheter/wire. This
      induces a temporary 'ligation' like effect so that the microcatheter can then be
      manipulated into the mastoid branch via the mastoid foramen. Rarely, the
      occipital artery has to be sacrificed if spasm cannot be induced or is short
      living, following which particles can be injected from a distance without
      entering the mastoid foramen. Occluding the occipital artery proximally has no
      effect on distal perfusion, as collaterals and anastomoses from superficial
      temporal artery, posterior auricular artery, and opposite occipital artery take
      over the supply.

PMID- 21897686
TI  - Optic neuropathy due to allergic fungal rhinosinusitis.
AB  - An uncommon case of allergic fungal rhinosinusitis presented to the ophthalmology
      outpatient department of our hospital with complaints of blurred vision in the
      right eye of a few days duration and vague complaints of pain around the eyes.
      The visual acuity on examination was grossly reduced in the right eye and normal
      in the left eye. Color vision was normal. Anterior segment examination including
      pupils was normal. Dilated fundus examination was normal except for temporal
      pallor in the right optic disc. Automated perimetry and magnetic resonance
      imaging (MRI) scan of brain and orbit were done. The imaging report showed a
      bilateral pansinusitis with pressure on the right optic nerve. Perimetry showed a
      superior field defect on the right side. ENT consultation and computed tomography
      (CT) with contrast helped to diagnose this as a case of allergic fungal
      rhinosinusitis. The patient was started on systemic steroids under the care of
      the ENT surgeon. After a few days, pre-operative assessment showed a gross
      improvement of visual acuity. Endoscopic sinus surgery was done to remove the
      polyps and thick mucus material. Histopathologic examination confirmed allergic
      fungal mucin. Days after surgery, the visual acuity improved further and repeat
      perimetry showed gross improvement in the visual field. Good history taking and a
      detailed ophthalmic examination, keeping in mind the probable causes of loss of
      vision of few days duration with no findings other than a decreased visual acuity
      and a suspicious disc, were key to the early diagnosis and investigation in this
      case. This helped in early referral and management of the case before permanent
      damage and irreversible visual loss occurred. The optic nerve is a cranial nerve
      which, once damaged permanently, will not regenerate. The amount of sinus
      involvement was extensive on both sides and invariably the left optic nerve would
      have been involved in a few days, if intervention was delayed.

PMID- 21897687
TI  - Bladder distension: An unusual cause of reflux of blood and hemodynamic changes
      (autonomic dysreflexia) during endovascular coiling.
AB  - Autonomic dysreflexia due to distended bladder is well known. Reflux of blood
      during endovascular procedure is also a common observation. It happens due to
      difference in pressure gradient between arterial pressure and that of infusing
      solution. Generally it happens when the infusion bottle is empty or the pressure
      in infusion bottles fall. We present an uncommon situation where distended
      bladder mechanically resulted in reflux of blood into endovascular catheters as
      well as alteration in hemodynamic parameters. Both settled once the bladder was
      empty.

PMID- 21897688
TI  - Cystic mature teratoma of the thoracic region in a child: An unusual case.
AB  - Cystic mature teratomas of the spinal cord are rare lesions. Teratomas account
      for up to 0.1% of all spinal cord tumors. Teratomas include tissues that
      originate from the three germ layers. Several congenital disorders may accompany
      the teratoma. Teratomas are classified as mature, immature or malignant type
      according to their histological characteristics. Thoracic spinal teratomas are
      uncommon in the pediatric age group. More than half of the patients are adults.
      We present herein a five-year-old male patient who was referred to our clinic
      with cystic mature teratoma at the T12 level.

PMID- 21897689
TI  - Mania associated with complicated hereditary spastic paraparesis.
AB  - Hereditary spastic paraparesis (HSP) is an inherited group of neurological
      disorders with progressive lower limb spasticity. HSP can be clinically grouped
      into pure and complicated forms. Pure HSP is one without any associated
      neurological/psychiatric comorbidity. Depression is the most common psychiatric
      comorbidity. Presence of mania or bipolar affective illness with HSP is a rare
      phenomenon. We report a case of a 17-year-old boy who presented with classical
      features of HSP with complaints of excessive happiness, irritability, increased
      self-esteem and decreased sleep since 1 month. The patient also had complex
      partial seizure ever since he had features of HSP. The patient's father and
      younger sister suffer from pure HSP. The patient was diagnosed to have first
      episode mania with complicated HSP. The details of treatment and possible
      neurobiology are discussed in this case report.

PMID- 21897690
TI  - Parkisonism followed by burr hole drainage for chronic subdural hemorrhage.
AB  - There have been few reports on secondary parkisonism caused by chronic subdual
      hemorrhage (CSDH). In most reports, rigidity-bradykinesia syndrome resolved
      gradually after decompressive operation for CSDH. We report a 74-year-old male
      patient who suffered from CSDH status post burr hole drainage twice, and followed
      secondary parkinsonism thereafter. Decompression by burr hole drainage was
      successful. However, the conscious level was still altered and the patient began
      to present with rigidity and bradykinesia. Fortunately, the symptoms dramatically
      improved after taking L-dopa. CSDH-related parkinsonism may have pre-operative
      nigrostriatal dysfunction, which can not compensate further insults to the basal
      ganglia. Prescription of L-dopa may be helpful in these patients.

PMID- 21897691
TI  - Holocord syringomyelia presenting as rapidly progressive foot drop.

PMID- 21897692
TI  - Commentary.

PMID- 21897693
TI  - Head injury management guidelines for general practitioners.
AB  - A complete examination of a head injured patient in the hospital requires a
      number of instruments. These include a stethoscope, sphygmomanometer,
      ophthalmoscope, otoscope, cotton wool, safety pin, tuning fork, reflex hammer and
      a small key to test the plantar response. Few of these are required at the
      accident scene. This is because, in the hospital, the aim is optimal definitive
      treatment. At the accident scene, the aim is prevention of secondary injury,
      rapid recording of the most important findings and safe efficient transport to
      the hospital. This short paper reviews how the local doctor should undertake a
      neurosurgical assessment of traumatic brain injury patients. Moreover, the
      primary management at accident scenes is described and the rationale behind the
      approach is outlined.

PMID- 21897694
TI  - Cephalic tetanus following tooth extraction in a Nigerian woman.

PMID- 21897695
TI  - Intracranial tuberculoma associated with subdural hematoma.

PMID- 21897696
TI  - Serpentine calcification: A radiological stigma.

PMID- 21897697
TI  - Acute inter-hemispheric subdural hematoma in a kabaddi player: A comment.

PMID- 21897698
TI  - Author's reply.

PMID- 21897699
TI  - Author's reply.

PMID- 21897700
TI  - Zidovudine-induced myopathy.

PMID- 21897701
TI  - Rehabilitation robotics in India.

PMID- 21897702
TI  - Work-related upper limb disorders: Can prevention and management be improved?

PMID- 21897703
TI  - Transient anisocoria: A pesky palpitation.

PMID- 21897704
TI  - The Google+ Project and neurosciences: Will it be as supercalifragilistic
      expialidocious as expected?

PMID- 21897705
TI  - A tale of too many strengths: Can we minimize prescribing errors and dispensing
      errors with so many formulations in the market?

PMID- 21897706
TI  - Rabeprazole and esomeprazole in mild-to-moderate erosive gastroesophageal reflux
      disease: A comparative study of efficacy and safety.
AB  - OBJECTIVE: To compare the efficacy and safety of rabeprazole and esomeprazole in
      mild-to-moderate erosive gastroesophageal reflux disease (GERD). MATERIALS AND
      METHODS: A randomized, single-blinded, outdoor-based clinical study was conducted
      on 60 patients of mild-to-moderate erosive GERD. After baseline clinical
      assessment and investigations, rabeprazole (40 mg) was prescribed to 30 patients
      and esomeprazole (40 mg) to another 30 patients for 4 weeks. The efficacy
      variables were change in GERD symptom scoring, endoscopic findings, and Quality
      of Life in Reflux and Dyspepsia (QOLRAD) scoring over 4 weeks. RESULT: Heartburn,
      acid regurgitation, and overall GERD symptom scoring (P = 0.01) were
      significantly decreased with rabeprazole in comparison to esomeprazole. The
      comparative study of all five domains of the QOLARD questionnaire including
      overall scoring revealed a statistically significant improvement in the
      rabeprazole group. Endoscopic findings in the rabeprazole group showed an
      absolute improvement of 30% and relative improvement of 55% over esomeprazole.
      Both the drugs were well tolerated having no significant difference in the
      incidence of adverse effects. CONCLUSION: Rabeprazole (40 mg) is a better choice
      for mild-to-moderate GERD compared with esomeprazole (40 mg) because of its
      better efficacy and safety profile.

PMID- 21897707
TI  - Antibiotic sensitivity profile of bacterial pathogens in postoperative wound
      infections at a tertiary care hospital in Gujarat, India.
AB  - OBJECTIVE: To find out the most common bacterial pathogens responsible for post
      operative wound infection and their antibiotic sensitivity profile. MATERIALS AND
      METHODS: This prospective, observational study was carried out in patients of
      postoperative wound infection. Samples from wound discharge were collected using
      a sterile swab and studied for identification of isolates by Gram stains and
      culture growth followed by in vitro antibiotic susceptibility testing performed
      by disc diffusion method on Mueller Hinton agar. RESULTS: Out of 183 organisms,
      126 (68.85%) isolated organisms were gram negative. Staphylococcus aureus, 48
      (26.23%), was the predominant organism. S. aureus was sensitive to rifampicin
      (89.58%), levofloxacin (60.42%), and vancomycin (54.17%). Pseudomonas aeruginosa
      was sensitive to ciprofloxacin (83.78%), gatifloxacin (51.35%), and meropenem
      (51.35%). Escherichia coli was sensitive to levofloxacin (72.41%) and
      ciprofloxacin (62.07%). Klebsiella pneumoniae was sensitive to ciprofloxacin
      (63.16%), levofloxacin (63.16%), gatifloxacin (63.16%), and linezolid (56.52%).
      Proteus mirabilis was sensitive to ciprofloxacin (75%) and linezolid (62.50).
      Proteus vulgaris was sensitive to ampicillin+sulbactam (57.14%) followed by
      levofloxacin (50%). CONCLUSIONS: There is an alarming increase of infections
      caused by antibiotic-resistant bacteria, particularly in the emergence of
      VRSA/VISA, meropenem, and third generation cephalosporin resistant Pseudomonas
      aeruginosa. Linezolid showing sensitivity against Gram negative bacteria.

PMID- 21897708
TI  - Comparison of McAuley/fasting insulin indices with ATP III clinical criteria for
      the diagnosis of insulin resistance in type 2 diabetes mellitus.
AB  - OBJECTIVE: To estimate the prevalence of insulin resistant syndrome (IRS) among
      newly diagnosed patients with type 2 diabetes and to test their validity against
      two indices of insulin resistance (IR). MATERIALS AND METHODS: Prevalence of IRS
      was estimated according to the criteria used by ATP III in newly diagnosed type 2
      diabetic patients. Sensitivity and specificity of the ACE criteria were
      calculated against two indices of IR namely fasting insulin (FI) level > 12 mU/l
      and McAuley index (McA) < 5.8. [McA= exp [2.63--0.28 ln(insulin in mU/l) -- 0.31
      ln(triglycerides in mmol/l)]. RESULTS: 35.7% of patients had IRS by ATP III
      criteria. 64.3% of patients were insulin resistant by FI and McA in each index.
      In patients who had IRS with ATP criteria, 80% and 86.6% were found to have McA
      and FI in the insulin resistant range. Out of the patients who were resistant by
      McA, only 40.6% had IR by ACE criteria and 93% had shown IR by FI. Out of all
      patients who did not fulfill the ATP III for IR, 74% and 59% were detected as
      having IR by fasting insulin and McA respectively. Sensitivity of the ACE
      criteria when tested against the FI and McA were 37.5% and 40.6%, specificity
      were 70% and 80%, respectively. CONCLUSIONS: IRS was common among the newly
      diagnosed patients with type 2 diabetes. ACE criteria showed an acceptable
      specificity but lack adequate sensitivity when compared with the two Indices of
      insulin resistance. More valid and clinically useful criteria should be available
      for the accurate diagnosis of IRS in clinical practice.

PMID- 21897709
TI  - Comparison of combinations of ciprofloxacin-metronidazole and ceftriaxone
      metronidazole in controlling operative site infections in obstetrics and
      gynecological surgeries: A retrospective study.
AB  - OBJECTIVE: To compare the effectiveness of the ciprofloxacin-metronidazole (CIP
      MET) regimen with the ceftriaxone-metronidazole (CEF-MET) regimen for operative
      site infection control in women undergoing obstetrical and gynecological
      surgeries. MATERIALS AND METHODS: One thousand and eighty-four case records of
      women who had undergone various obstetrical and gynecological surgeries who were
      given CIP-MET regimen and CEF-MET regimen were analyzed in predesigned and
      pretested proforma. Patients who were given CIP-MET regimen and CEF-MET regimen
      were classified as Group 1 and Group 2 respectively. The mode of administration
      of both the regimens was noted. Numbers of wound infections were recorded in the
      respective groups. Socioeconomic status and hemoglobin level of the patients were
      noted. Other data such as hospital stay, duration of operation were also noted.
      RESULTS: Out of a total of 1084 case records, 31 (5.8%) and eight (0.7%) patients
      contracted wound infections in Group 1 and Group 2 respectively (P = 0.0001).
      CONCLUSION: The CEF-MET regimen was found superior to the CIP-MET regimen to
      control operative site infection in obstetrical and gynecological surgeries.

PMID- 21897711
TI  - A comparative study of reliability of self report of tobacco use among patients
      with bipolar and somatoform disorders.
AB  - OBJECTIVE: To compare the use and reliability of self-reported tobacco use (both
      smoked and smokeless) among patients with bipolar disorder and somatoform
      disorders. MATERIALS AND METHODS: The study was conducted at psychiatry out
      patient department of a tertiary care hospital. A total of 50 consecutive
      patients were recruited. The subjects were asked about the use of tobacco
      products (smoked as well as smokeless) over the past one week. Those reporting
      affirmatively in response to the question were assessed using Fagerstrom Test for
      Nicotine Dependence (FTND) scales. Quantitative urinary cotinine levels were
      assessed using Enzyme-linked immunosorbent assay (ELISA). RESULTS: Calculation of
      Cohen's kappa using cross tabulation revealed discordance between the self
      reported use of smoked as well as smokeless tobacco products in both the groups.
      Analysis using the lower cut off of 50 ng/ ml also revealed discordance between
      the self-reported tobacco use (smoked as well as smokeless) for both the groups.
      CONCLUSIONS: The reliability of self-report is questionable among both these
      groups for smoking as well as smokeless tobacco products.

PMID- 21897712
TI  - Comparative anti-ulcerogenic study of pantoprazole formulation with and without
      sodium bicarbonate buffer on pyloric ligated rat.
AB  - OBJECTIVE: To compare the anti-ulcer activity of buffered pantoprazole tablet
      against plain pantoprazole in pyloric ligated rats. MATERIALS AND METHODS: In
      vivo pyloric ligated ulcerogenesis model was used to assess the effect of
      buffered pantoprazole on the volume of the gastric content, pH, total and free
      acidity, and ulcerogenic lesion. Pantoprazole level in gastric content and
      concurrently in stomach tissue was assessed by High Performance Liquid
      Chromatography (HPLC) analysis. RESULTS: Buffered tablet effectively increases
      the pH of the gastric content above 4 up to 6 h (P<0.001) protecting pantoprazole
      from acid degradation resulting in high concentration in the gastric content and
      stomach tissue. CONCLUSIONS: This study substantiates better, faster and
      prolonged bioavailability of pantoprazole-buffered tablet compared to plain
      pantoprazole.

PMID- 21897713
TI  - Deep vein thrombosis in a woman taking oral combined contraceptive pills.
AB  - Oral combined contraceptive pill (OCCP) is popular as birth control pills. Like
      all other drugs, they are not free from risks. Women taking certain types of OCCP
      have higher risk of developing deep vein thrombosis (DVT). A 29 year old married
      woman had taken OCCP for 3.5 months, developed deep vein thrombosis of left leg.
      Hereditary and acquired causes of DVT were excluded. She was treated with
      parenteral and oral anticoagulants simultaneously and was advised to discontinue
      OCCP. Initially the risk of blood clot was believed to be due to dose of estrogen
      but recent study relates it to the type of progesterone involved in OCCP. Thus,
      it is still a matter of debate, whether to associate risk of DVT to the amount of
      estrogen alone or also to the type of progestin. Apart from careful selection of
      patients, one should also look for the risk of venous thromboembolism
      irrespective of type of OCCP prescribed.

PMID- 21897714
TI  - Cross sensitivity between ciprofloxacin and levofloxacin for an immediate
      hypersensitivity reaction.
AB  - Seven years old male child (24 kg weight) diagnosed as a case of sub acute
      appendicitis treated with ciprofloxacin, immediately developed multiple
      erythmatous papules. Reaction subsided after withholding ciprofloxacin and
      treatment with dexamethasone and chlorpheneramine maleate. It was developed again
      when treated with levofloxacin and subsided after withdrawal. IgE binding at
      7(th) position of core structure of fluoroquinolones likely to be the mechanism.
      As all the fluoroquinolones have similar core structure, hypersensitivity to one
      may have cross sensitivity to other fluoroquinolones. It is advisable to avoid
      other fluoroquinolones and switch over to other group of antibiotics when
      hypersensitivity to one occurs.

PMID- 21897715
TI  - Accidental staggered paracetamol overdose: An interesting case report.
AB  - Paracetamol is one of the most commonly used drugs both over the counter and on
      prescription. Liquid paracetamol is available over the counter all over the
      world. Most commonly available concentrations are 120 mg/5 ml and 250 mg/5 ml.
      Many parents and healthcare professionals assume that doses available in
      different countries are similar. However, 500 mg/5 ml bottle is available in some
      countries including the United Kingdom. This leaves a potential for accidental
      overdose with therapeutic intent. We have reviewed the experience of diagnosing
      and managing an interesting case of paracetamol over dosage caused by several
      ingestions over 24 hours period (staggered paracetamol over dosage). It
      highlights the importance of communication between health professionals and
      parents while managing common medical problems.

PMID- 21897716
TI  - Fumaria indica is safe during chronic toxicity and cytotoxicity: A preclinical
      study.

PMID- 21897717
TI  - Drug promotional literature distributed by pharmaceutical companies: Do they
      provide enough information to ascertain their validity?

PMID- 21897718
TI  - Remembering what's new in Alzheimer's management.

PMID- 21897719
TI  - Unused medicines in Nigerian households: Types and disposal practices.

PMID- 21897720
TI  - Adverse drug reaction monitoring in a tertiary care teaching hospital.

PMID- 21897721
TI  - Effect of chronic administration of low dose aspirin on haloperidol induced
      catalepsy in rats.

PMID- 21897722
TI  - Anti-inflammatory, analgesic, and antioxidant activities of methanolic wood
      extract of Pterocarpus santalinus L.

PMID- 21897723
TI  - Anti-inflammatory and analgesic activities of stem bark extracts of Eugenia
      jambolana.

PMID- 21897724
TI  - Drug use in elderly patients: Are we there yet?

PMID- 21897725
TI  - Author's Reply.

PMID- 21897726
TI  - Fingolimod (Gileyna, FTY720): Innovative treatment for multiple sclerosis.

PMID- 21897727
TI  - Ceftaroline fosamil: A novel anti-Methicillin-resistant Staphylococcus aureus
      cephalosporin.

PMID- 21897728
TI  - Alliance for human research protection.

PMID- 21897729
TI  - Measures of central tendency: Median and mode.

PMID- 21897730
TI  - From super-specialist to generalist? The way forward.

PMID- 21897731
TI  - Yoga: An evidence-based therapy.

PMID- 21897733
TI  - Bladder outlet obstruction in women.
AB  - Bladder outlet obstruction in females remains a poorly understood condition and
      is much rarer as compared to males. More difficult is the objective diagnosis of
      this condition. There is no general agreement on the Urodynamic parameters to
      define the condition with certainty. A number of conditions are involved
      particularly in urinary retention in females are not completely understood.
      Besides, external sphincter dysfunction and post surgical retentions add another
      group of conditions which are distinct from retentions seen in the males. This
      article takes a review of various aetiological factors of Bladder outlet
      obstruction in women. An attempt is made to standardise the Urodynamic parameters
      for use in females, based on our data and experimentation on the models of the
      bladder and urethra. This article also takes a review of uncommon conditions such
      as Fowler's syndrome which often complicate evaluation of this condition.

PMID- 21897732
TI  - Role of probiotics in urogenital healthcare.
AB  - Urogenital infections are one of the most common causes for a woman to visit a
      gynecologist or a urologist. The well-known association between abnormal vaginal
      microbial flora and its formidable risk in the increased incidence of urinary
      tract infection underscores the importance of understanding the microbial flora
      and the efforts needed to maintain it, for ensuring urogenital health.
      Surprisingly in spite of the increased incidence urogenital infections receive
      very less attention from the medical fraternity. Growing awareness among people
      and newer advances in the medical field has brought them into the limelight. The
      importance of replenishing these depleting commensals with 'probiotics' has
      resurfaced in a big way. As the days go by science and medicines will touch new
      milestones, which will include probiotics. The value of a probiotics cannot be
      taken at face value. Probiotics must not be considered a panacea for treating
      urogenital infections. However, the available data promises that it will be a
      strong option in improving and maintaining urogenital health.

PMID- 21897734
TI  - Moral and professional responsibility of oral physician toward geriatric patient
      with interdisciplinary management - The time to act is now!
AB  - Mouth is the mirror of overall health. With advancements in oral health promotion
      and preventive measures instituted in developed countries, more people retain
      their natural teeth into their old age as compared to half a century ago. The
      effect of aging on oral health includes effect on oral mucosa, lips, teeth and
      other associated structures, and their functional activity leading to impairment
      of speech, mastication, swallowing and pain leading to anxiety and depression.
      Oral tissues are not limited to the teeth and supporting structures
      (periodontium) but also include salivary glands, temporomandibular joint,
      orofacial/mastication muscles, oropharyngeal mucosa, and oral sensory/motor nerve
      systems. In India, the second most populous country in the world, there is a
      rapidly growing population of older adults and there are 70 million elderly
      people over 60 years of age. Geriatric health problems with respect to the
      quality of life often remain neglected. Oral health care for an increasingly
      large segment of elderly people will be a fact of life for dentists everywhere.
      Oral health can be both a benchmark for and a determinant of the quality of life
      rather than the length of life span. Older adults are more susceptible to oral
      conditions or diseases due to an increase in chronic conditions and
      physical/mental disabilities. Thus, a careful initial interview ensuring that the
      dentist is familiar with the patient's health history, followed by a thorough
      oral examination plays a very important role. In this paper, we briefly review
      the age-related oral changes occurring in geriatric patients and the role of oral
      physician in imparting a healthy life to the elderly.

PMID- 21897735
TI  - A randomized trial of vaginal misoprostol for cervical priming before
      hysteroscopy in postmenopausal women.
AB  - OBJECTIVE: To perform hysteroscopy the cervix needs to be dilated and in
      nullipara and postmenopausal women this is sometimes difficult. Well-known, entry
      related complications during hysteroscopy include cervical tear, creation of
      false tract, bleeding, uterine perforation, scarring, and subsequent anatomical
      stenosis. MATERIALS AND METHODS: This study was done to investigate the priming
      effect of vaginal misoprostol on cervical dilatation in postmenopausal women,
      before hysteroscopy, to prevent such complications. Two hundred micrograms of
      misoprostol was inserted into the vagina at least 12 hours before the procedure
      and the control group did not receive any cervical priming agent. Pre-procedural
      dilatation, additional dilatation required, and time taken for dilatation was
      noted in each case. OBSERVATIONS: The study showed a significant difference
      between the study group (7.7 +/- 1.7 mm) and the control group (4.5 +/- 1.8 mm)
      in terms of pre-procedural cervical width and the number of women requiring a
      dditional dilatation (7 / 25 versus 22 / 25), and hence, the time required for
      dilatation (4.7 +/- 8 seconds versus 20.6 +/- 9.3 seconds). CONCLUSION: The pre
      procedural cervical width was significantly more in the study group as compared
      to that in the control group. We found significant differences between the study
      and control groups with respect to the number of women who required cervical
      dilatation. To conclude, this study helps derive a conclusion that vaginal
      misoprostol as a cervical priming agent in postmenopausal women appears to be
      safe, effective, and inexpensive, with mild side effects.

PMID- 21897736
TI  - Yoga therapy for developing emotional intelligence in mid-life managers.
AB  - BACKGROUND: Business executives' lives have become a never-ending race against
      time, technology, and targets. This race creates tension, which leads to
      dissatisfaction and frustration and eventually manifests itself as psychological
      and physiological stress with mental and emotional drain. This modern lifestyle
      intensifies the stress leading to "excessive tension" and consequent
      deterioration in "executive efficiency". OBJECTIVE: To assess emotional
      intelligent quotient (EQ) in managers undergoing yoga-based Self Management of
      Excessive Tension (SMET) program. MATERIALS AND METHODS: 72 managers participated
      in this study which is of "single group pre-post design." The EQ test developed
      by Prof N. K. Chadha from University of Delhi was administered as pre and post
      the 5 days of SMET program. STATISTICAL ANALYSIS: Means, standard deviations,
      Kolmogorov-Smirnov test, and Wilcoxon signed rank test were used to analyze the
      data. RESULTS: The data analysis showed 72.02% significant increase (P<0.001) in
      EQ. CONCLUSION: The results suggest that participation in a SMET program was
      associated with improvement in EQ and may have implications for "executive
      efficiency."

PMID- 21897737
TI  - Junctures to the therapeutic goal of diabetes mellitus: Experience in a tertiary
      care hospital of Kolkata.
AB  - INTRODUCTION: The World Health Organization has declared India as the "diabetic
      capital" of the world. In controlling of such chronic, mostly asymptomatic
      disease, patients' role can't be overemphasized. AIMS: To assess the level of
      compliance to anti-diabetic therapies and to ascertain the determinants of non
      compliance, if any. MATERIALS AND METHODS: A cross-sectional observational study
      was conducted for 3 months in a diabetic clinic of R G Kar Medical College and
      Hospital, Kolkata. Data were collected by interviewing the patients, examining
      their prescriptions and laboratory reports and anthropometry after obtaining
      informed consent. RESULTS: Blood report at the point of data collection revealed
      controlled glucose homeostasis in 38.93% patients but evaluation of past 3 months
      report showed only 24.3% had control over hyperglycemia. Glycemic control was
      seen to be positively related to short duration of disease, compliance to
      therapies, and high knowledge about diabetes. Compliance to therapies found in
      32.22% of study subjects was in turn associated with short duration of disease.
      House-wives showed poor compliance; insulin treatment with or without oral-anti
      diabetic agent showed better compliance. Knowledge of diabetes was significantly
      high among higher educated; poor among women, house-wives, and rural people.
      CONCLUSION: Patient-providers collaboration is to be developed through a patient
      centered care model based on the mutual responsibility of both so that each
      patient is considered in the mesh of his/her other goals of life and helped to
      promote empowerment to take informed decision for behavioral change conducive to
      control the disease.

PMID- 21897738
TI  - A rare case of irreparable vesico-vaginal fistula of 45 years duration
      successfully managed by urinary diversion.
AB  - In developing countries most of the fistulas occur as a catastrophic complication
      of obstructed labor in young women. Constant dribbling, wetness, and stink lead
      to social outcasting of patients of vesico-vaginal fistula (VVF) making their
      life miserable. In most of the cases, timely surgery taking all required
      precautions is successful. In small number of cases, fistula is irreparable.
      Under such circumstances urinary diversion helps. Very few cases are reported in
      literature, where patients have endured fistula for more than 40 years. A case
      report of a patient of VVF, who suffered for 45 years without seeking any
      treatment because of prevailing circumstances is presented here. The fistula was
      irreparable. Urinary diversion was the only option available. She was
      successfully managed by urinary diversion with an ileal conduit. Now patient is
      leading a contented life.

PMID- 21897739
TI  - Brenner tumor of ovary: An incidental finding.
AB  - Brenner tumor is a rare ovarian tumor that is a part of the surface epithelial
      group of ovarian neoplasm. It is usually asymptomatic and most of the times it is
      an incidental pathological finding. Here we present a case of benign Brenner
      tumor of ovary treated surgically.

PMID- 21897740
TI  - Vaginal leiomyoma.
AB  - Leiomyomas are common benign tumors in the uterus. However, vaginal leiomyomas
      remain an uncommon entity with only about 300 reported cases. Here, we report a
      case of a 38-year-old multigravida who presented with lower abdominal pain and
      vaginal bleeding. A physical examination and ultrasonography were performed, and
      a diagnosis of cervical fibroid was made. Pervaginal removal of the tumor was
      performed and subsequent histopathology revealed a vaginal leiomyoma. Although a
      rare tumor, vaginal leiomyomas may present with a variety of clinical features
      and may be mistaken preoperatively for cervical fibroid. Removal of tumor by
      vaginal route, wherever possible, with subsequent histopathological examination
      appears to be the optimum management plan.

PMID- 21897741
TI  - Story of Mrs. VR who did not have stress urinary incontinence.

PMID- 21897742
TI  - Thirteenth world congress on menopause, rome, 8 - 11 june, 2011.

PMID- 21897743
TI  - Quantitative in vivo and ex vivo confocal microscopy analysis of corneal cystine
      crystals in the Ctns knockout mouse.
AB  - PURPOSE: The purpose of this study was to assess the ability of quantitative in
      vivo confocal microscopy to characterize the natural history and detect changes
      in crystal volume in corneas from a novel animal model of cystinosis, the
      cystinosin (Ctns(-/-)) mouse. METHODS: Two Ctns(-/-) mice and one C57Bl/6 mouse
      were examined at each of the following time points: 2, 3, 5, 7, 10, 12, and 14
      months of age. In vivo confocal microscopy scans were performed in 4 different
      regions of the cornea per eye. After, animals were sacrificed and cornea blocks
      evaluated for cell morphology using phalloidin and lymphocytic infiltration using
      CD45 antibodies by ex vivo confocal microscopy. Cystine crystal content in the
      cornea was measured by calculating the pixel intensity of the crystals divided by
      the stromal volume using Metamorph Image Processing Software. RESULTS: Corneal
      crystals were identified in Ctns(-/-) eyes beginning at 3 months of age and
      increased in density until 7-12 months, at which time animals begin to succumb to
      the disease and corneas become scarred and neovascularized. Older Ctns(-/-) mice
      (7 months and older) showed the presence of cell infiltrates that stained
      positively for CD45 associated with progressive keratocyte disruption. Finally,
      at 12 months of age, decreased cell density and endothelial distortion were
      detected. CONCLUSIONS: Confocal microscopy identified corneal crystals starting
      at 3 month old Ctns(-/-) eyes. Cystine crystals induce inflammatory and immune
      response with aging associated with loss of keratocyte and endothelial cells.
      These findings suggest that the Ctns(-/-) mouse can be used as a model for
      developing and evaluating potential alternative therapies for corneal cystinosis.

PMID- 21897744
TI  - Topical application of L-arginine blocks advanced glycation by ascorbic acid in
      the lens of hSVCT2 transgenic mice.
AB  - PURPOSE: Previous experiments from our laboratory showed that the oral intake of
      selected guanidino compounds could block the formation of crystallin-bound
      advanced ascorbylation products. Here we tested whether these were also active
      when applied as eye drops. METHODS: Two month old hSVCT2 transgenic mice (n=10)
      were treated twice daily with one drop of 0.1% L-arginine, gamma-guanidinobutyric
      acid (GBA), penicillamine (PA) or N-acetylcysteine (NAC) in one eye and vehicle
      only in the other eye. After seven months, lens crystallins were isolated,
      dialyzed, and proteolytically digested to determine the protein-bound
      fluorescence at 335/385 and 370/440 nm excitation/emission and the advanced
      glycation/ascorbylation endproducts carboxymethyl-lysine (CML), carboxyethyl
      lysine (CEL), glucosepane, glyoxal, and methylglyoxal hydroimidazolones G-H1 and
      MG-H1. The topical uptake of L-arginine and NAC was also evaluated in vitro and
      in vivo in rabbit lens. RESULTS: In hSVCT2 mice, L-arginine decreased 335/385 and
      370/440 nm fluorescence by 40% (p<0.001), CML, CEL, and glucosepane crystallin
      crosslinks by 35% (p<0.05), 30% (p<0.05), and 37% (p<0.05), respectively, without
      affecting MG-H1 and G-H1. NAC decreased 335/385 nm fluorescence by 50% (p<0.001)
      but, like PA and GBA, had no effect on other modifications. L-Arginine uptake
      into rabbit eyes treated topically reached identical lenticular plateau levels
      (~400 nmol/g wet weight) at 0.5% and 2.0% but levels remained three times higher
      at 5 h at 2% versus 0.5% concentration, respectively. In vitro studies showed a
      100 fold higher L-arginine level than NAC levels, implicating high affinity
      uptake of the former. CONCLUSIONS: L-Arginine when applied both orally and
      topically is a potent and broad suppressor of advanced ascorbylation in the lens.
      Its uptake in rabbit lens upon topical application suggests transcorneal uptake
      into the human lens should be feasible for testing its potential anticataract
      properties in clinical trials.

PMID- 21897745
TI  - Expression and cellular localization of microRNA-29b and RAX, an activator of the
      RNA-dependent protein kinase (PKR), in the retina of streptozotocin-induced
      diabetic rats.
AB  - PURPOSE: The apoptosis of retinal neurons plays a critical role in the
      pathogenesis of diabetic retinopathy (DR), but the molecular mechanisms
      underlying this phenomenon remain unclear. The purpose of this study was to
      investigate the cellular localization and the expression of microRNA-29b (miR
      29b) and its potential target PKR associated protein X (RAX), an activator of the
      pro-apoptotic RNA-dependent protein kinase (PKR) signaling pathway, in the retina
      of normal and diabetic rats. METHODS: Retinas were obtained from normal and
      diabetic rats within 35 days after streptozotocin (STZ) injection. In silico
      analysis indicated that RAX is a potential target of miR-29b. The cellular
      localization of miR-29b and RAX was assessed by in situ hybridization and
      immunofluorescence, respectively. The expression levels of miR-29b and RAX mRNA
      were evaluated by quantitative reverse transcription PCR (qRT-PCR), and the
      expression of RAX protein was evaluated by western blot. A luciferase reporter
      assay and inhibition of endogenous RAX were performed to confirm whether RAX is a
      direct target of miR-29b as predicted by the in silico analysis. RESULTS: We
      found that miR-29b and RAX are localized in the retinal ganglion cells (RGCs) and
      the cells of the inner nuclear layer (INL) of the retinas from normal and
      diabetic rats. Thus, the expression of miR-29b and RAX, as assessed in the retina
      by quantitative RT-PCR, reflects their expression in the RGCs and the cells of
      the INL. We also revealed that RAX protein is upregulated (more than twofold) at
      3, 6, 16, and 22 days and downregulated (70%) at 35 days, whereas miR-29b is
      upregulated (more than threefold) at 28 and 35 days after STZ injection. We did
      not confirm the computational prediction that RAX is a direct target of miR-29b.
      CONCLUSIONS: Our results suggest that RAX expression may be indirectly regulated
      by miR-29b, and the upregulation of this miRNA at the early stage of STZ-induced
      diabetes may have a protective effect against the apoptosis of RGCs and cells of
      the INL by the pro-apoptotic RNA-dependent protein kinase (PKR) signaling
      pathway.

PMID- 21897746
TI  - Enhanced S-cone function with preserved rod function: a new clinical phenotype.
AB  - PURPOSE: To describe the clinical findings and genetic analysis in two brothers
      having a novel retinal disease characterized by an enhanced S-cone phenotype with
      normal rod function. METHODS: Both patients underwent complete ophthalmologic
      examinations, including fundus photography, electroretinography (ERG),
      fluorescein angiography and optical coherence tomography (OCT). Mutation analysis
      of the following candidate genes was performed: nuclear receptor subfamily 2
      group E member 3 (NR2E3), neural retina leucine zipper (NRL), nuclear receptor
      subfamily 1 group D member 1 (NR1D1), and thyroid hormone receptor beta (THRB).
      RESULTS: Spectral photopic ERG responses demonstrated enhanced S-cone function in
      both patients. Their scotopic b-wave ERG amplitude responses, however, were
      within normal limits. Their scotopic a-wave amplitude responses were within the
      lower limit of normal. The a- and b-wave latencies were normal for one sibling
      and on the upper limit of normal for the other. Peripheral retinal findings were
      normal. OCT showed flattening of the macular curvature and thinning of the
      photoreceptor layer. Mutation analysis of NR2E3, NRL, NR1D1, and THRB genes was
      negative. CONCLUSIONS: We describe what appears to be a previously unidentified
      familial retinal phenotype with enhanced S-cone function and well preserved rod
      system function in contrast to the severely reduced rod function seen in the
      enhanced S-cone syndrome (ESCS). Genetic analysis of candidate genes did not
      reveal the cause of disease. We postulate that the disease might be caused by
      mutation of another, as yet unidentified gene, which encodes a protein that
      functions as a negative inhibitor of rod and S-cone development.

PMID- 21897747
TI  - The association of hepatocyte growth factor (HGF) gene with primary angle closure
      glaucoma in the Nepalese population.
AB  - PURPOSE: Genetic variation in the hepatocyte growth factor (HGF) gene has
      recently been associated with hyperopia, which is a known risk factor for primary
      angle closure glaucoma (PACG). This study aimed to investigate whether genetic
      variation in HGF is associated with primary angle closure glaucoma in the
      Nepalese population. METHODS: One hundred six Nepalese patients with primary
      angle closure glaucoma and 204 matched controls were recruited. Twelve tag single
      nucleotide polymorphisms (SNPs) were selected and genotyped to cover the majority
      of common variation within HGF. Genotype and haplotype analyses were conducted in
      PLINK. RESULTS: Four HGF SNPs were found to be significantly associated with
      PACG, rs5745718, rs12536657, rs12540393 and rs17427817 (p=0.002, 0.002, 0.0006,
      and 0.0006, respectively). In addition, haplotype analysis showed one common
      haplotype to be significantly associated with PACG (p=0.001) in this population.
      CONCLUSIONS: Genetic variation in HGF is associated with PACG in the Nepalese
      population. Additional replication studies in other populations are necessary to
      confirm this association and to further explore the role of HGF in the
      pathogenesis of this blinding disease.

PMID- 21897748
TI  - A recurrent missense mutation in GJA3 associated with autosomal dominant cataract
      linked to chromosome 13q.
AB  - PURPOSE: To map and identify the genetic defect underlying autosomal dominant
      cataract segregating in a 5-generation Caucasian American family. METHODS:
      Genomic DNA was prepared from blood leukocytes, genotyping was performed using
      microsatellite markers, and logarithm of the odds (LOD) scores were calculated
      using the LINKAGE programs. Mutation profiling was performed using direct exon
      cycle-sequencing and restriction fragment analysis. Protein function effects were
      evaluated using in silico prediction algorithms. RESULTS: Significant evidence of
      linkage was obtained at marker D13S175 (maximum LOD score [Z(max)]=3.67; maximum
      recombination fraction [theta(max)]=0.04) and D13S1316 (Z(max)=2.80,
      theta(max)=0.0). Haplotyping indicated that the disease lay in the ~170 Kb
      physical interval between D13S1316 and D13S175, which contained the gene for gap
      junction protein alpha-3 (GJA3) or connexin-46. Sequencing of GJA3 detected a
      heterozygous transition (c.130G>A) in exon-2 that resulted in gain of an Hsp92 II
      restriction site. Allele-specific PCR amplification and restriction analysis
      confirmed that the novel Hsp92 II site co-segregated with cataract in the family
      but was not detected in 192 normal unrelated individuals. The c.130G>A transition
      was predicted to result in a non-conservative substitution of valine-to
      methionine at codon 44 (p.V44M) with damaging effects on protein function.
      CONCLUSIONS: These data confirm GJA3 as one of the most frequently mutated genes
      that underlie autosomal dominant cataract in humans, and further emphasize the
      importance of connexin function in maintaining lens transparency.

PMID- 21897749
TI  - S100A expression in normal corneal-limbal epithelial cells and ocular surface
      squamous cell carcinoma tissue.
AB  - PURPOSE: To study the expression and cellular distribution of multiple S100A
      genes and proteins in normal corneal-limbal epithelium and ocular surface
      squamous cell carcinoma (SCC) tissue. METHODS: Normal corneal-limbal tissue was
      obtained from the Lions Eye Bank, Tampa, FL. Ocular surface SCC tissues were
      excised from patients undergoing surgery at Singapore National Eye Centre. S100A
      mRNA expression was measured by quantitative PCR. S100 protein distribution was
      determined by immunofluorescent staining analysis. RESULTS: Twelve S100 mRNAs
      were identified in human corneal and limbal epithelial cells. S100A2, A6, A8, A9,
      A10, and A11 mRNA was expressed at high level, while S100A1, A3, A4, A5, A6, A7,
      and A12 mRNA expression was low. The intracellular localization of S100A2, A6,
      A8, A9, A10 and A11 protein was determined in normal corneal-limbal and SCC
      tissues. S100A2 and S100A10 proteins were enriched in basal limbal epithelial
      cells of the normal tissue. S100A8 and S100A9 were found only at the surface of
      peripheral corneal and limbal epithelium. S100A6 was uniformly found at the
      plasma membrane of corneal and limbal epithelial cells. S100A11 was found at the
      supralayer limbal epithelial cells adjacent to the conjunctiva. SCC tissue showed
      typical pathological changes with expression of cytokeartin (CK) 14 and CK4 in
      the epithelial cells. All SCC epithelial cells were positive of S100A2, S100A10,
      S100A6 and S100A11 staining. Intracellular staining of S100A8 and S100A9 was
      found in several layers of SCC epithelium. Expression of S100A2 and S100A10
      decreased dramatically in cultured limbal epithelial cells with increased
      passaging, which was accompanied by a small increase of S100A9 mRNA, with no
      changes of S100A8 gene expression. Serum and growth hormone depletion of the
      culture serum caused a small reduction of S100A2 and S100A10 gene expression,
      which was accompanied by a small increase of S100A9 mRNA while no changes of
      S100A8 expression was measured. CONCLUSIONS: Normal corneal and limbal epithelial
      cells express a broad spectrum of S100 genes and proteins. Ocular surface SCC
      express high levels of S100A2, S100A10, S100A8 and S100A9 proteins. The
      expression of S100A2 and S100A10 is associated with limbal epithelial cell
      proliferation and differentiation.

PMID- 21897750
TI  - Is the dietary protein restriction achievable in chronic kidney disease? The
      impact upon quality of life and the dialysis delay.
AB  - The possible deleterious effect of meet consumption upon deterioration of renal
      disease was speculated from Lionel Beale as early as 1869. The first attempt to
      apply a very low protein diet in humans is attributed to Millard Smith who
      prescribed a diet consisting of 300 mg protein per day in a volunteer medical
      student for 24 days. Unfortunately, in early 20(th) century, prescribing very low
      protein diets among patients suffering from renal disease complicated with
      malnutrition and the medical practice of this era turned to the recommendation of
      high protein diets because it was believed that protein consumption is coupled
      with the strength of civilized man. In mid sixties Giordano and Giovanetti
      introduced low protein diets in the treatment of uremic patients but their
      efforts did not accepted from the medical community. Meanwhile the evolution of
      haemodialysis, peritoneal dialysis and transplantation as effective methods of
      treating end stage renal disease guided doctors and patients far from privative
      diets in the era of plenty. The rapidly increasing number of end stage renal
      disease patients needed substitution of renal function produced a tremendous
      increase of financial burden upon public health system expenditure and
      alternative measures of therapy, prevention and delaying chronic kidney disease
      searched. Unfortunately MDRD study failed to show convincing results of food
      protein restriction and blood pressure lowering in ameliorating deterioration of
      renal function and the majority of physicians turned to the practice of early
      dialysis in an attempt to avoid malnutrition. Despite the increasing knowledge
      and the appliance of certain guidelines in treating end stage renal disease
      patients, the morbidity and mortality remain high among this population. The
      search toward other possible toxic substances showed that phosphorus consumption
      with diet is another dangerous element exerting its deleterious effect in
      deteriorating renal function as well as increasing morbidity and mortality.
      Recently published epidemiological data suggest a very poor outcome of elderly
      patients, older than 80 years of age, undergoing substitution of renal function
      by dialysis or peritoneal dialysis and a lot of skepticism arise concerning the
      beneficial effect of diet and a rigorous effort of rehabilitation of these
      patients instead of substitution of renal function by either method.

PMID- 21897751
TI  - Pregnancy in women with renal disease. Yes or no?
AB  - Women with renal disease who conceive and continue pregnancy, are at significant
      risk for adverse maternal and fetal outcomes. Although advances in antenatal and
      neonatal care continue to improve these outcomes, the risks remain proportionate
      to the degree of underlying renal dysfunction.The aim of this article, is to
      examine the impact of varying degrees of renal insufficiency on pregnancy
      outcome, in women with chronic renal disease and to provide if possible, useful
      conclusions whether and when, a woman with Chronic Kidney Disease (CKD), should
      decide to get pregnant.This article, reviews briefly the normal physiological
      changes of renal function during pregnancy, and make an attempt to clarify the
      nature and severity of the risks, in the settings of chronic renal insufficiency
      and end stage renal disease, including dialysis patients and transplant
      recipients.

PMID- 21897752
TI  - Is the underutilization of peritoneal dialysis in relation to hemodialysis, as
      renal replacement therapy, justifiable worldwide? Yes or No.
AB  - Peritoneal dialysis is the most important home dialysis treatment for end stage
      renal diseases and needs personal involvement, and support from the family .
      Peritoneal dialysis presented a number of discouraging technical problems and led
      to the belief that PD was not an appropriate renal replacement therapy, for
      patients with end stage renal disease. Despite the improvement of the method its
      rate remain low (11%) worldwide. The factors affecting the choice of PD are
      multiple and explain the disparity in the use of peritoneal dialysis in different
      countries and different parts of the same country. Dialysis costs and
      reimbursement structures are significant in decisions about the rates and
      modalities of renal replacement therapy. Late referral and the health care system
      seems to be very important factors that influence the dialysis modality choice.
      After the initiation of peritoneal dialysis we can see other factors that
      influence the survival of the method. The rate of peritonitis and the peritoneum
      function seems to be important issues.

PMID- 21897753
TI  - The effect of the expenditure increase in the morbidity and the mortality of
      patients with end stage renal disease: the USA case.
AB  - The worldwide incidence of kidney failure is on the rise and treatment is costly.
      Kidney failure patients require either a kidney transplant or dialysis to
      maintain life. This review focuses on the economics of alternative dialysis
      modalities such as haemodialysis (HD) and peritoneal dialysis (PD). Important
      economic factors influencing dialysis modality selection include financing,
      reimbursement and resource availability. Modality selection is also influenced by
      employment status, with an association between being employed and PD as the
      modality choice.In the United States, there were 101,688 incident HD patients and
      6,506 incident PD patients in 2007. Due to the fact that the worldwide incidence
      of kidney failure continues to rise placing USA in the second position right
      after Taiwan, the accumulated experience from USA could be used as a
      characteristic prototype for the analysis of the economics related with modality
      choices and their influence in the quality of life and life expectancy of end
      stage renal disease (ESRD) patients.In the present work we discuss the effect of
      the expenditure increase in the morbidity and the mortality of patients with end
      stage renal disease. Data coming from the USA case concerning the economic
      factors which play a vital role in the sequence of events that leads to the
      choice between different modalities such as HD and PD, will be used as a
      distinctive example in our study. The relationship between the modality used and
      employment status is investigated. The cost effectiveness of alternative
      modalities is reviewed. Examples of statistical models and simulation approaches,
      studying the increase of the life expectancy in terms of the quality adjusted
      life years (QALYs) and the incremental cost paid are also presented.
      Corresponding results originated from different regions of the world are also
      briefly shown.

PMID- 21897754
TI  - Phosphate binders: Sevelamer in the prevention and treatment of
      hyperphosphataemia in chronic renal failure.
AB  - In chronic kidney disease patients, bone and mineral abnormalities have a major
      impact on morbidity and mortality. Hyperphosphatemia has been associated with
      increased mortality and with the development of cardiovascular calcification, an
      independent predictor of mortality. Sevelamer, or more precisely 'sevelamer
      hydrochloride', is a weakly basic anion-exchange resin in the chloride form that
      was introduced in 1997 for the treatment of the hyperphosphataemia of patients
      with end-stage renal failure. Sevelamer sequesters phosphate within the
      gastrointestinal tract, so prevents its absorption and enhances its faecal
      excretion. Over the succeeding years, large numbers of patients have been treated
      with sevelamer, and it has fulfilled expectations in helping to control the
      hyperphosphataemia of end-stage renal failure. Additionally treatment with
      sevelamer was accompanied with lower incidence of hypercalcemia, decreased
      incidence of low PTH levels, a 15-31% decrease of LDL-cholesterol both in
      dialysis and predialysis patients, decreased C-reactive protein, amelioration of
      hyperuricemia and low fetuin A, decrease of uremic toxins, suggesting an overall
      anti-inflammatory effect. In incident dialysis patients, treatment with sevelamer
      has been associated with better survival, while in prevalent patients a clear
      benefit could only be demonstrated in older patients and in patients treated for
      more than 2 years. In dialysis patients, the treatment of hyperphospathemia with
      calcium based compounds, when compared with sevelamer, is associated with more
      frequent episodes of hypercalcemia, suppression of intact PTH and with
      progression of coronary calcifications. In the presence of adynamic bone disease,
      calcium load has a significantly higher impact on aortic calcifications and
      stiffening. Sevelamer treatment resulted in no statistically significant changes
      in bone turnover or mineralization compared with calcium carbonate, but bone
      formation rate increased and trabecular architecture improved only with
      sevelamer. In conclusion, the treatment of hyperphosphatemia with sevelamer
      hydrochloride, a noncalcium and non-metal containing phosphate binder, is
      associated with a beneficial effect on vascular calcification progression, bone
      disease and most likely with a survival benefit in some hemodialysis patients
      populations. Sevelamer carbonate is an improved, buffered form of sevelamer
      hydrochloride developed for the treatment of hyperphosphataemia in CKD patients.
      Sevelamer carbonate formulated as a powder for oral suspension presents a novel,
      patient- friendly alternative to tablet phosphate binders. Safety and efficacy of
      sevelamer carbonate powder compared with sevelamer hydrochloride tablets in CKD
      patients are equivalent, with Sevelamer carbonate having fewer side effects from
      gastrointestinal tract.

PMID- 21897755
TI  - Role of angiotensin converting enzyme inhibitors and angiotensin receptor
      blockers in hypertension of chronic kidney disease and renoprotection. Study
      results.
AB  - Chronic kidney disease (CKD) is a global health problem associated with
      considerable morbidity and mortality and despite advances in the treatment of end
      stage renal disease (ESRD) mechanisms to prevent and delay its progression are
      still being sought. The renin-angiotensin-aldosterone system (RAAS) plays a
      pivotal role in many of the pathophysiologic changes that lead to progression of
      renal disease. Traditionally RAAS was considered as an endocrine system and its
      principal role was to maintain blood pressure (BP). In recent years local RAAS
      has been described to operate independently from systemic and local angiotensin
      II (AngII) in the kidney to contribute in hypertension and kidney damage. The
      benefits of strict BP control in slowing kidney disease progression have been
      demonstrated in several clinical trials and the question whether specific agents
      like angiotensin converting enzyme antagonists (ACEIs) and angiotensin receptor
      blockers (ARBs) provide renoprotective benefits beyond BP lowering is to be
      answered. Several studies support these agents reduce proteinuria and protect
      renal function, whereas the opposite is stated by others. According to
      guidelines, their use is recommended as first line agents in diabetic renal
      disease and non diabetic renal disease with albuminuria, whereas there is no data
      to support the same in non diabetic nonalbuminuric renal disease. Dual blockage
      of RAAS with the combination of ACEIs and ARBs could offer an alternative in
      strict RAAS blockade, but studies up to now can not prove its safety and the
      combination is not recommended until ongoing trials will provide new and
      unarguable results.

PMID- 21897756
TI  - Secondary hyperparathyroidism and target organs in chronic kidney disease.
AB  - Secondary hyperparathyroidism (SHPT) is a common disorder in patients with
      chronic kidney disease (CKD) and is characterized by excessive serum parathyroid
      hormone (PTH) levels, parathyroid hyperplasia and an imbalance in calcium and
      phosphorus metabolism. Secondary hyperparathyroidism develops early in the course
      of CKD and becomes more prominent as kidney function declines.PTH is a major
      uremic toxin and may be responsible for long-term consequences that include renal
      osteodystrophy, severe vascular calcifications, alterations in cardiovascular
      structure and function, immune dysfunction, and anemia. These adverse effects may
      contribute to an increased risk of cardiovascular morbidity and mortality among
      end-stage renal failure patients.

PMID- 21897757
TI  - Renal anemia: a nephrologist's view.
AB  - Anemia is a common finding in patients with CKD, with a prevalence that increases
      gradually as eGFR declines. The prevalence of renal anemia depends on the size of
      the study and the selection of participants. Diabetic status increases the
      prevalence of anemia in patients with CKD. Anemia in CKD is due primarily to
      reduced production of erythropoietin in the kidney and secondarily to shortened
      red cell survival. Erythropoeitin (EPO) is produced by peritubular cells in the
      kidneys of the adult and in hepatocytes in the fetus. These cells are sensitive
      to hypoxia that once sensed leads to an increase in EPO production. EPO
      circulates in the plasma and induces redcell production in the bone marrow after
      successful binding to erythroid progenitor cells. Apart from EPO, folate, B(12)
      and iron are needed to assure effective erythropoiesis. Factors that can
      dysregulate this process include inflammation, uremic toxins, hypothyroidism,
      hypersplenism and ongoing infection.The investigation of renal anemia requires
      the assessment of a variety of biological indices. Among them, the complete blood
      count, the reticulocyte index, B(12), folate, ferritin levels and the saturation
      of transferrin are the most valuable tools in revealing the cause of renal
      anemia.

PMID- 21897759
TI  - Phosphorus metabolism in chronic kidney disease.
AB  - The knowledge about the exact mechanisms involved in phosphorus homeostasis and
      the evolution of secondary hyperparathyroidism in chronic kidney disease (CKD)
      has improved during the last years. The discovery of Fibroblast Growth Factor 23
      (FGF23) has revolutionized our understanding about the links between mineral
      metabolism, vitamin D and parathyroid hormone (PTH). FGF23 serum levels increase
      early in CKD before the increase of serum phosphorus or the decrease of vitamin D
      and there is parathyroid resistance to FGF23 in advanced CKD. Increased levels of
      serum phosphorus have been related in epidemiological studies with adverse
      outcomes in patients with CKD, diabetes, coronary artery disease, or even normal
      adults. In patients with CKD stage 3 or 4, low phosphorus diets have been related
      with adverse outcomes due to the risk of malnutrition and there are limited data
      regarding the role of phosphate binders in these patients. Recent studies suggest
      that increased serum FGF23 levels are associated with mortality, left ventricular
      hypertrophy and progression of CKD independently of serum phosphorus levels.
      There is an ongoing debate about the "normal" or "desirable" levels of serum
      phosphorus in CKD and a new role of FGF23 as a marker of the disturbances of
      mineral metabolism in CKD is emerging.

PMID- 21897758
TI  - Are we satisfied with the follow-up of hypertensive and chronic kidney disease
      patients in outpatient clinics?
AB  - Hypertension and chronic kidney disease constitute major health problems as they
      are associated with increased morbidity and mortality. Large-scale clinical
      trials, have emphasized the need of a strict blood pressure and early recognition
      of kidney disease to reduce the complications. However, the rate of hypertension
      control seems to be low, the prevalence of hypertension and chronic kidney
      disease steadily increases, indicating a gap in the management of those patients.
      This is due either to a poor organization of the health care system or a
      defective patient-physician communication. This review will try to identify
      possible errors in the management of hypertensive and renal failure patients in
      outpatient clinics and to propose ways to improve prevention and control of
      hypertension and chronic kidney diseases in our population.

PMID- 21897760
TI  - Update of acute kidney injury: intensive care nephrology.
AB  - Albeit the considerable progress that has been made both in our understanding of
      the pathophysiology of acute renal failure (ARF) and in its treatment (continuous
      renal replacement therapies), the morbidity of this complex syndrome remains
      unacceptably high. The current review focuses on recent developments concerning
      the definition of ARF, new strategies for the prevention and pharmacological
      treatment of specific causes of ARF, dialysis treatment in the intensive care
      setting and provides an update on critical care issues relevant to the clinical
      nephrologist.

PMID- 21897761
TI  - Adverse event profiles of platinum agents: data mining of the public version of
      the FDA adverse event reporting system, AERS, and reproducibility of clinical
      observations.
AB  - OBJECTIVE: Adverse event reports (AERs) submitted to the US Food and Drug
      Administration (FDA) were reviewed to confirm platinum agent-associated adverse
      events, and to clarify the rank-order of these drugs in terms of susceptibility.
      METHODS: After a revision of arbitrary drug names and the deletion of duplicated
      submissions, AERs involving cisplatin (CDDP), carboplatin (CBDCA), or oxaliplatin
      (L-OHP) were analyzed. Authorized pharmacovigilance tools were used for the
      quantitative detection of signals, i.e., drug-associated adverse events,
      including the proportional reporting ratio, the reporting odds ratio, the
      information component given by a Bayesian confidence propagation neural network,
      and the empirical Bayes geometric mean. RESULTS: Based on 1,644,220 AERs from
      2004 to 2009, CDDP, CBDCA, and L-OHP all proved to cause nausea, vomiting, acute
      renal failure, neutropenia, thrombocytopenia, and peripheral sensory neuropathy.
      Higher susceptibility to nausea was found for CDDP than CBDCA and L-OHP. Acute
      renal failure was also more predominant for CDDP, and CBDCA did not increase the
      blood level of creatinine. A stronger association with thrombocytopenia was
      suggested for CBDCA. Susceptibility to peripheral sensory neuropathy was greatest
      for L-OHP, but less extensive for CDDP and CBDCA. CONCLUSION: The results
      obtained herein were consistent with clinical observations, suggesting the
      usefulness of the FDA's adverse event reporting system, AERS, and the data mining
      method used herein.

PMID- 21897762
TI  - Translational medicine and reliability of single-nucleotide polymorphism studies:
      can we believe in SNP reports or not?
AB  - BACKGROUND: The number of genetic association studies is increasing
      exponentially. Nonetheless, genetic association reports are prone to potential
      biases which may influence the reported outcome. AIM: We hypothesized that
      positive outcome for a determined polymorphism might be over-reported across
      genetic association studies analysing a small number of polymorphisms, when
      compared to studies analysing the same polymorphism together with a high number
      of other polymorphisms. METHODS: We systematically reviewed published reports on
      the association of glutathione s-transferase (GST) single-nucleotide
      polymorphisms (SNPs) and cancer outcome. RESULT: We identified 79 eligible
      trials. Most of the studies examined the GSTM1, theGSTP1 Ile105Val mutation, and
      GSTT1polymorphisms (n = 54, 57 and 46, respectively). Studies analysing one to
      three polymorphisms (n = 39) were significantly more likely to present positive
      outcomes, compared to studies examining more than 3 polymorphisms (n=40) p =
      0.004; this was particularly evident for studies analysing the GSTM1polymorphism
      (p =0.001). We found no significant associations between journal impact factor,
      number of citations, and probability of publishing positive studies or studies
      with 1-3 polymorphisms examined. CONCLUSIONS: We propose a new subtype of
      publication bias in genetic association studies. Positive results for genetic
      association studies analysing a small number of polymorphisms (n = 1-3) should be
      evaluated extremely cautiously, because a very large number of such studies are
      inconclusive and statistically under-powered. Indeed, publication of misleading
      reports may affect harmfully medical decision-making and use of resources, both
      in clinical and pharmacological development setting.

PMID- 21897763
TI  - Oral rehydration therapy for preoperative fluid and electrolyte management.
AB  - AIM: Preoperative fluid and electrolyte management is usually performed by
      intravenous therapy. We investigated the safety and effectiveness of oral
      rehydration therapy (ORT) for preoperative fluid and electrolyte management of
      surgical patients. METHODS: The study consisted of two studies, designed as a
      prospective observational study. In a pilot study, 20 surgical patients consumed
      1000 mL of an oral rehydration solution (ORS) until 2 h before induction of
      general anesthesia. Parameters such as serum electrolyte concentrations,
      fractional excretion of sodium (FENa) as an index of renal blood flow, volume of
      esophageal-pharyngeal fluid and gastric fluid (EPGF), and patient satisfaction
      with ORT were assessed. In a follow-up study to assess the safety of ORT, 1078
      surgical patients, who consumed ORS until 2 h before induction of general
      anesthesia, were assessed. RESULTS: In the pilot study, water, electrolytes, and
      carbohydrate were effectively and safely supplied by ORT. The FENa value was
      increased at 2 h following ORT. The volume of EPGF collected following the
      induction of anesthesia was 5.3+/-5.6 mL. In the follow-up study, a small amount
      of vomiting occurred in one patient, and no aspiration occurred in the patients.
      CONCLUSION: These results suggest that ORT is a safe and effective therapy for
      the preoperative fluid and electrolyte management of selected surgical patients.

PMID- 21897764
TI  - A case report on eosinophilic meningitis caused by Angiostrongylus cantonensis.
AB  - Angiostrongylus cantonensis is the most common cause of eosinophilic meningitis
      in humans. It is usually caused by ingestion of raw or inadequately cooked
      intermediate hosts or food contaminated with infective third-stage larvae. We
      describe a case of eosinophilic meningitis caused by A. cantonensis in a male
      Chinese patient. The patient had a history of eating raw fish and snail. We
      describe the clinical features of the patient, the diagnostic process and
      treatments. We also provide a brief update for physicians on the characteristics,
      diagnosis and treatment of eosinophilic meningitis caused by A. cantonensis, with
      particular emphasis on the update of prevalence and treatment of the disease in
      China.

PMID- 21897765
TI  - Impairment of pulmonary function is an independent risk factor for atrial
      fibrillation: the Takahata study.
AB  - BACKGROUND: Chronic pulmonary disorders, such as chronic obstructive pulmonary
      disease (COPD) and fibrosing lung diseases, and atrial fibrillation (AF), are
      prevalent in elderly people. The impact of cardiac co-morbidities in the elderly,
      where pulmonary function is impaired, cannot be ignored as they influence
      mortality. The relationship between the prevalence of AF and pulmonary function
      is unclear. The aim of this study was to evaluate this relationship in
      participants in a health check. METHODS: Subjects aged 40 or older (n = 2,917)
      who participated in a community-based annual health check in Takahata, Japan,
      from 2004 through to 2005, were enrolled in the study. We performed blood
      pressure measurements, blood sampling, electrocardiograms, and spirometry on
      these subjects. RESULTS: The mean FEV(1) % predicted and FVC % predicted in AF
      subjects was significantly lower than in non-AF subjects. The prevalence of AF
      was higher in those subjects with airflow limitation or lung restriction than in
      those without. Furthermore, AF prevalence was higher in those subjects with
      severe airflow obstruction (FEV(1) %predicted < 50) than in those who had mild or
      moderate airflow obstruction (FEV(1) %predicted >= 50), although there was no
      difference between the prevalence of AF in subjects with 70<= FVC %predicted <80
      lung restriction and those with FVC %predicted <70. Multiple logistic regression
      analysis revealed that FEV(1) %predicted and FVC %predicted are independent risk
      factors for AF (independent of age, gender, left ventricular hypertrophy, and
      serum levels of B-type natriuretic peptide). CONCLUSION: Impaired pulmonary
      function is an independent risk factor for AF in the Japanese general population.

PMID- 21897766
TI  - Methylenetetrahydrofolate reductase gene polymorphisms in children with attention
      deficit hyperactivity disorder.
AB  - OBJECTIVE: The purpose of this study was to evaluate the relationship between
      5,10- methylenetetrahydrofolate reductase (MTHFR) polymorphisms and Attention
      Deficit Hyperactivity Disorder (ADHD) in a sample of Turkish children. STUDY
      DESIGN: MTHFR gene polymorphisms were assessed in 40 patients with ADHD and 30
      healty controls. Two mutations in the MTHFR gene were investigated using
      polymerase chain reactions and restriction fragment length polymorphisms.
      RESULTS: Although there were no statistically significant differences in genotype
      distributions of the C677T alleles between the ADHD and the control groups
      (p=0,678) but the genotypic pattern of the distributions of the A1298C alleles
      was different between the ADHD patients and the controls (p=0,033). CONCLUSIONS:
      Preliminary data imply a possible relationship between A1298C MTHFR polymorphisms
      and the ADHD.

PMID- 21897769
TI  - Preventing childhood obesity: wake up, it's time for sleep!

PMID- 21897768
TI  - Caffeine and screen time in adolescence: associations with short sleep and
      obesity.
AB  - OBJECTIVE: To investigate the associations between sleep duration and obesity
      incidence and risk factors among pre-adolescents and adolescents. DESIGN: Cross
      sectional study of a community based cohort SETTING: The Tucson Children's
      Assessment of Sleep Apnea follow-up study (TuCASA) cohort. PARTICIPANTS: 319
      Caucasian and Hispanics between 10-17 years. MAIN OUTCOME: Parent-reported sleep
      duration and BMI z-score. OUTCOME MEASURES: Surveys of electronic screen time,
      dietary and caffeine intake, exercise and sleep habits by parents, and
      anthropometric measures. RESULTS: Parent-reported total sleep time (TST) was
      inversely associated with BMI z-score, but not significantly correlated with any
      of the examined nutritional variables or exercise components. Hispanic ethnicity
      was associated with significantly lower parent-reported TST and higher BMI z
      score. Parent-reported TST was inversely related to electronic screen time and
      caffeine use, but these findings were differentially related to age. Caffeine
      consumption was associated with decreasing parent-reported TST primarily in older
      adolescents. Electronic screen time was associated with lower parent-reported TST
      in younger adolescents. CONCLUSIONS: Hispanic ethnicity and parental reports of
      TST were found to be the most closely associated with BMI z-score. Decreased TST
      and increased caffeine intake and screen time may result in higher obesity risk
      in the adolescent population.

PMID- 21897770
TI  - Caregivers' knowledge, behavior, and attitudes regarding healthy sleep in young
      children.
AB  - STUDY OBJECTIVES: To examine sleep health knowledge and beliefs and their
      relationship to sleep practices in a community sample of caregivers of young
      children. METHODS: A convenience sample of caregivers visiting a museum on one of
      2 consecutive weekend days completed a brief parent-report survey on child sleep
      habits and parental basic sleep knowledge and beliefs and attitudes regarding
      sleep as a health behavior. RESULTS: Of the 253 analyzable surveys (response rate
      80%; mean age of index child 3.4 +/- 2.0 years), 23% of children did not have a
      consistent bedtime, 25% had a bedtime later than 9 pm, 23% had at least one
      electronic device in the bedroom, and 56% frequently fell asleep with an adult
      present. Both positive and negative sleep habits tended to cluster together.
      Children who had irregular and late bedtimes were more than twice as likely to
      obtain insufficient sleep that those with regular and early bedtimes (OR 2.30,
      2.45). While 25% of children were getting less than the recommended sleep amount
      for age, just 13% of parents believed that their child was getting insufficient
      sleep. Lack of knowledge regarding the potential negative impact of specific
      sleep practices was associated with an increased likelihood of engaging in those
      practices. CONCLUSIONS: The results of this survey study of a generally well
      educated sample of caregivers suggest that there are clear parental knowledge
      gaps regarding healthy sleep in young children and supports the need for
      increased sleep health education.

PMID- 21897771
TI  - Teen sleep and suicidality: results from the youth risk behavior surveys of 2007
      and 2009.
AB  - STUDY OBJECTIVES: Suicide in the adolescent population is a tragic and
      preventable cause of death. Previous studies have confirmed both long and short
      total sleep times (TSTs) are associated with suicidal ideation in the adult
      population. We hypothesized that both long and short TSTs are risk factors for
      serious suicide attempt in the adolescent population as well. METHODS: We tested
      this hypothesis using the Youth Risk Behavior Surveys from 2007 and 2009, which
      consist of school-based, nationally representative samples (N = 12,154 for 2007,
      N = 14,782 for 2009). Logistic regression models were used to assess the
      relationship between suicidality and sleep after adjusting for confounders
      including age, sex, race/ethnicity, feelings of sadness, and substance abuse.
      RESULTS: Of the total sample, roughly 15% reported suicidal ideation, 10% planned
      suicide, 5% attempted and 2% reported an attempt requiring treatment. Teens who
      reported sleeping <= 5 or >= 10 h had a significantly higher risk for suicidality
      compared to those with a TST of 8 h. The largest odds ratios were found among the
      most severe forms of suicidality (attempt requiring treatment) with an odds ratio
      of 5.9 for a TST <= 4 h and 4.7 for a TST >= 10 h. CONCLUSION: Both short and
      long TSTs are risk factors for suicidality among teens and extremes in TST may
      indicate more serious suicidality. Self-reported sleep duration may be a useful
      screening question for suicide risk. Future studies should examine whether sleep
      duration is a causal and/or modifiable risk factor for suicidality in teens.

PMID- 21897773
TI  - A possible method to predict response to non-pharmacological insomnia therapy.
AB  - STUDY OBJECTIVES: To determine if electrocardiographic parameters are predictive
      of response to non-pharmacological insomnia therapy. DESIGN: Secondary analysis
      of heart rate parameters from a double blind, randomized, sham-controlled trial
      at multiple study sites. SETTING: Six sites in the United States were used for
      the data collection. PARTICIPANTS: One hundred ninety-eight healthy subjects with
      no sleep disorders. INTERVENTIONS: Subjects were studied on 2 consecutive nights,
      a baseline night and a therapy night. On the therapy night, subjects were phase
      advanced 4 h and randomized to receive either sham or vestibular stimulation, an
      experimental therapy for insomnia. MEASUREMENTS AND RESULTS: ECG data were
      recorded and analyzed for the 5-min periods preceding and following sleep onset.
      Analyses were conducted on those who did and did not respond to therapy, as
      defined by latency from bedtime to persistent sleep (LPS). Responders to therapy
      were found to have higher low-frequency (LF) power at baseline during wakefulness
      than non-responders, and responders had higher high-frequency (HF) power during
      therapy than non-responders on therapy. Furthermore, responders > 35 y had
      elevated LF power at baseline than non-responders > 35 y (p < 0.05). No
      differences were seen in the sham group in identical analyses, ruling out a
      nonspecific effect of sleep onset. CONCLUSIONS: Heart rate variability analyses
      indicate that differences exist between those who respond to insomnia therapy and
      those that do not, particularly in an older subset of subjects. Further research
      into the use of ECG and other physiological parameters to stratify response to
      therapeutic interventions is warranted.

PMID- 21897772
TI  - Factors that may influence the classification of sleep-wake by wrist actigraphy:
      the MrOS Sleep Study.
AB  - STUDY OBJECTIVES: Total sleep time (TST), sleep efficiency (SE), sleep latency
      (SOL) and wake after sleep onset (WASO) assessed by actigraphy gathered in 3
      different modes were compared to polysomnography (PSG) measurements to determine
      which mode corresponded highest to PSG. Associations of measurement error for TST
      (PSG-actigraphy) with demographics, medical history, exam data, and sleep
      characteristics were examined. METHODS: Participants underwent in-home 12-channel
      PSG. Actigraphy data were collected in 3 modes: proportional integration mode
      (PIM), time above threshold (TAT) and zero crossings mode (ZCM). The analysis
      cohort was a subgroup of 889 men (mean age 76.4 years) from the MrOS Sleep Study
      with concurrently measured PSG and actigraphy. Intraclass correlation
      coefficients (ICCs) were used to compare the association between PSG and
      actigraphy. RESULTS: The PIM mode of actigraphy corresponded moderately to PSG
      for all measures (ICCs 0.32 to 0.57), TAT a little lower (ICCs 0.17 to 0.47), and
      ZCM lower still (ICCs 0.16 to 0.33). The PIM mode corresponded best to PSG (ICCs
      TST 0.57; SE 0.46; SOL 0.23; WASO 0.54), though the estimations from PSG and PIM
      mode differed significantly (p < 0.01). The PIM mode overestimated TST by 13.2
      min on average, but underestimated TST for those in certain subgroups: those with
      excessive daytime sleepiness, less sleep fragmentation, or more sleep disordered
      breathing (p < 0.05). CONCLUSIONS: Sleep parameters from the PIM and TAT modes of
      actigraphy corresponded reasonably well to PSG in this population, with the PIM
      mode correlating highest. Systematic measurement error was observed within
      subgroups with different sleep characteristics.

PMID- 21897774
TI  - Accurate position monitoring and improved supine-dependent obstructive sleep
      apnea with a new position recording and supine avoidance device.
AB  - STUDY OBJECTIVES: Approximately 30% of obstructive sleep apnea (OSA) patients
      have supine-predominant OSA, and simply avoiding supine sleep should normalise
      respiratory disturbance event rates. However, traditional supine-avoidance
      therapies are inherently uncomfortable, and treatment adherence is poor and
      difficult to monitor objectively. This study evaluated the efficacy of a novel,
      potentially more acceptable position monitor and supine-avoidance device for
      managing supine-predominant OSA and snoring. DESIGN AND SETTING: In-laboratory
      evaluation of position recording accuracy versus video recordings (validation
      study), and randomized controlled crossover trial of active versus inactive
      supine-avoidance therapy in the home setting (efficacy study). PATIENTS: 17
      patients undergoing in-laboratory sleep studies (validation) and 15 patients with
      supine-predominant OSA (efficacy). INTERVENTIONS: EFFICACY STUDY: 1 week of
      inactive and 1 week of active treatment in randomized order, separated by 1 week.
      MEASUREMENTS AND RESULTS: Agreement between 30-sec epoch-based posture
      classifications from device versus video records was high (median kappa 0.95,
      interquartile range: 0.88-1.00), and there was good supine time agreement (bias
      0.3%, 95%CI: -4.0% to 4.6%). In the efficacy study, apnea-hypopnea index (AHI)
      and snoring frequency were measured in-home using a nasal pressure and microphone
      based system during inactive and active treatment weeks. The position monitoring
      and supine alarm device markedly inhibited supine time (mean +/- SEM 19.3% +/-
      4.3% to 0.4% +/- 0.3%, p < 0.001) and reduced AHI (25.0 +/- 1.7 to 13.7 +/- 1.1
      events/h, p = 0.030) but not snoring frequency. CONCLUSIONS: This new position
      monitoring and supine alarm device records sleep position accurately and improves
      OSA but not snoring in patients with supine-predominant OSA.

PMID- 21897775
TI  - Evaluation of a single-channel portable monitor for the diagnosis of obstructive
      sleep apnea.
AB  - STUDY OBJECTIVE: To validate the ApneaLINK (AL) as an accurate tool for
      determining the presence of obstructive sleep apnea (OSA) in an at-risk sleep
      clinic population in a home test environment. METHODS: Consecutive participants
      referred with the suspicion of OSA were evaluated in the home with the AL
      portable monitor (AL Home), followed by simultaneous data collection with
      diagnostic polysomnography (PSG) and AL in the sleep laboratory (AL Lab).
      Prevalence, sensitivity, specificity, and ROC curves were calculated for PSG vs.
      AL Lab, PSG vs. AL Home, and AL Lab vs. AL Home test. Pearson correlations and
      Bland-Altman plots were constructed. RESULTS: Fifty-three (55% female)
      participants completed the entire study. The mean age of the population was 45.1
      +/- 11.3 years, and body mass index was 35.9 +/- 9.1 kg/m(2). The prevalence of
      an apnea hypopnea index (AHI) >= 15 in the cohort was 35.9%. The results
      demonstrated a high sensitivity and specificity of the AL respiratory disturbance
      index (RDI-AL) compared with the AHI from the PSG. The AL Lab had the highest
      sensitivity and specificity at RDI-AL values >= 20 events/h (sensitivity 100%,
      specificity 92.5%). The AL Home was most sensitive and specific at an RDI-AL >=
      20 events/h (sensitivity 76.9%, specificity 92.5%). The Pearson correlations for
      PSG vs. AL Lab and PSG vs. AL Home were rho = 0.88 and rho = 0.82, respectively.
      The Bland-Altman Plots demonstrated good agreement between the methodologies.
      CONCLUSION: The AL home test is an accurate alternative to PSG in sleep clinic
      populations at risk for moderate and severe OSA. TRIAL REGISTRATION:
      clinicaltrials.gov ID: NCT00354614.

PMID- 21897777
TI  - Effect of continuous positive airway pressure on an atrial arrhythmia in a
      patient with mild obstructive sleep apnea.
AB  - Cardiac arrhythmias have been reported in up to half of individuals with
      obstructive sleep apnea (OSA) and have been proposed to be one of the factors
      contributing to their increased mortality. Several studies have demonstrated
      evidence of an association between OSA and a number of cardiac arrhythmias. The
      mechanisms of arrhythmogenesis in OSA may be due to enhanced vagal output
      triggered by a combination of apnea and hypoxemia. This case demonstrates a dose
      dependent reduction in atrial ectopy with increasing continuous positive airway
      pressure (CPAP) in the setting of mild sleep apnea.

PMID- 21897776
TI  - Membrane level of omega-3 docosahexaenoic acid is associated with severity of
      obstructive sleep apnea.
AB  - BACKGROUND: Patients with obstructive sleep apnea (OSA) are at increased risk of
      cardiovascular disease (CVD). The omega-3 fatty acid docosahexaenoic acid (DHA)
      is a major component of neural tissues, and supplementation with fish oils
      improves autonomic tone and reduces risk for CVD. A link between low DHA status
      and less mature sleep patterns was observed in newborns. METHODS: We investigated
      the relations between red blood cell (RBC) levels of DHA and OSA severity in 350
      sequential patients undergoing sleep studies. Severity categories were defined as
      none/mild, moderate, and severe, based on apnea hypopnea index (AHI) scores of 0
      to 14, 15 to 34, and > 34, respectively. RESULTS: After controlling for age, sex,
      race, smoking, BMI, alcohol intake, fish intake, and omega-3 supplementation, RBC
      DHA was inversely related with OSA severity. For each 1-SD increase in DHA
      levels, a patient was about 50% less likely to be classified with severe OSA. The
      odds ratios (95% CI) were 0.47 (0.28 to 0.80) and 0.55 (0.31 to 0.99) for being
      in the severe group versus the none/mild or moderate groups, respectively.
      CONCLUSION: These findings suggest that disordered membrane fatty acid patterns
      may play a causal role in OSA and that the assessment of RBC DHA levels might
      help in the diagnosis of OSA. The effects of DHA supplementation on OSA should be
      explored.

PMID- 21897778
TI  - Resolution of papilledema associated with OSA treatment.
AB  - Obstructive sleep apnea (OSA) is a common disorder and is associated with brain
      functional and morphological alterations. The association between OSA and
      papilledema, however, is not well known. We describe a 53-year-old morbidly obese
      female who presented with impaired vision due to bilateral papilledema.
      Polysomnography revealed severe OSA. She was treated with continuous positive
      airway pressure, and within a few weeks her papilledema and vision improved. This
      case report is consistent with association of OSA with papilledema but does not
      prove causality.

PMID- 21897780
TI  - Dangerous driver.

PMID- 21897779
TI  - Obstructive sleep apnea and respiratory complications associated with vagus nerve
      stimulators.
AB  - Intermittent vagus nerve stimulation can reduce the frequency of seizures in
      patients with refractory epilepsy. Stimulation of vagus nerve afferent fibers can
      also cause vocal cord dysfunction, laryngeal spasm, cough, dyspnea, nausea, and
      vomiting. Vagus nerve stimulation causes an increase in respiratory rate,
      decrease in respiratory amplitude, decrease in tidal volume, and decrease in
      oxygen saturation during periods of device activation. It usually does not cause
      an arousal, or a change in heart rate or blood pressure. Most patients have an
      increase in their apnea-hypopnea index (AHI). Patients with VNS can have central
      apneas, obstructive hypopneas, and obstructive apneas. These respiratory events
      can be reduced with changes in the vagus nerve stimulator operational parameters
      or with the use of CPAP. In summary, there are complex relationships between
      epilepsy and obstructive sleep apneas. In particular, patients with refractory
      epilepsy need assessment for undiagnosed and untreated obstructive sleep apnea
      before implantation of vagus nerve stimulator devices. Patients with vagus nerve
      stimulators often have an increase in apneic events after implantation, and these
      patients need screening for sleep apnea both before and after implantation.

PMID- 21897781
TI  - Acupuncture may be helpful only for patients with comorbid insomnia secondary to
      chronic pain syndromes.

PMID- 21897783
TI  - Healthcare "practice"-is it misguided?

PMID- 21897784
TI  - Sodium oxybate: updates and correction to previously published safety data.

PMID- 21897785
TI  - Sodium oxybate post-marketing surveillance.

PMID- 21897788
TI  - Pseudocyst in the pancreatic tail associated with chronic pancreatitis
      successfully treated by transpapillary cyst drainage.
AB  - We report a 50-year-old male with pseudocysts in the pancreatic tail associated
      with chronic pancreatitis successfully treated by transpapillary cyst drainage.
      He had previously undergone ultrasonography-guided percutaneous cyst drainage for
      a pancreatic pseudocyst in our hospital. He was readmitted due to abdominal pain
      and fever. Computed tomography showed recurrence of a pseudocyst in the
      pancreatic tail measuring 5 cm in diameter. Since conservative treatment failed,
      endoscopic retrograde pancreatography was performed. There was communication
      between the pseudocyst and the main pancreatic duct, and pancreatic duct stenosis
      proximal to the pseudocyst. First, transpapillary pancreatic duct drainage was
      performed using a plastic stent, but the pseudocyst did not decrease in size and
      became infected. After removal of the stent, a pigtail type nasocystic catheter
      was placed in the pseudocyst via the pancreatic duct. The pseudocyst infection
      immediately disappeared, and the pseudocyst gradually decreased and disappeared.
      After removal of the nasocystic catheter, no recurrence was observed. As
      transpapillary drainage of pancreatic pseudocyst, cyst drainage and pancreatic
      duct drainage have been reported. In our patient with pseudocyst in the
      pancreatic tail, duct drainage was ineffective and the pseudocyst was infected,
      whereas cyst drainage was very effective. We considered that cyst drainage by a
      nasocystic catheter was the first-line therapy as the transpapillary drainage of
      the pancreatic pseudocyst.

PMID- 21897789
TI  - Celiac disease and myointimal proliferation: a possible correlation?
AB  - Celiac disease (CD) is an autoimmune disorder of the small bowel that occurs in
      genetically predisposed people of all ages, from middle infancy, and is caused by
      a reaction to gliadin, a gluten protein. Some patients are diagnosed with
      symptoms related to the decreased absorption of nutrients or with various
      symptoms which, although statistically linked, have no clear relationship with
      the malfunctioning bowel. Classic symptoms of CD include diarrhea, weight loss,
      and fatigue; bowel symptoms may be limited or even absent. In this article we
      describe the case of a young woman with CD who presents with myointimal
      proliferation. However multiple cases of vessel thrombosis have been reported in
      patients with CD. Despite the fact that no definitive relationship between these
      diseases could be explained, we think this association must be remembered
      especially in cases of young and tenuous women with these vascular abnormalities.

PMID- 21897790
TI  - Groove Pancreatitis with Several Cystic Lesions around the Pancreatic Head
      Treated Conservatively: Report of a Case.
AB  - A 61-year-old man was admitted to our hospital with epigastric pain and vomiting.
      Enhanced abdominal computed tomography revealed inflammatory change of the
      pancreatic groove and focal wall thickening of the second portion of the duodenum
      with several cystic lesions around the head of the pancreas. We diagnosed
      atypical type of groove pancreatitis. The patient made a satisfactory recovery by
      conservative medication treatment for acute on chronic pancreatitis and cystic
      lesions disappeared in parallel with pancreatitis. Groove pancreatitis is a rare
      form of chronic pancreatitis, and to the best of our knowledge, our patient is
      the first case in the English literature of groove pancreatitis with cystic
      lesions around the head of the pancreas, which disappeared after conservative
      treatment for pancreatitis.

PMID- 21897791
TI  - Leukocytoclastic vasculitis as an onset symptom of Crohn's disease.
AB  - We report the case of an octagenerian who presented with leukocytoclastic
      vasculitis as the first symptom of Crohn's disease. The patient was admitted with
      skin rash on the lower extremities and ankles and episodes of bloody diarrhea.
      Skin and colon biopsies revealed acute leukocytoclastic vasculitis and moderate
      Crohn's disease, respectively. The patient was treated with intravenous
      corticosteroids in conjunction with antibiotics and per os mesalazine. Symptoms
      resolved rapidly within 5 days, and the patient was still asymptomatic on follow
      up 3 months later.

PMID- 21897792
TI  - Primary aorto-duodenal fistula as a late complication of radiotherapy: report of
      a case and review of the literature.
AB  - Primary aorto-duodenal fistula (PADF) is a rare condition that may result in
      rapid exsanguination if untreated. PADF due to radiotherapy appears to be
      extremely rare with only a few cases reported in the medical literature. We
      report the case of a 61-year-old man who presented with massive gastrointestinal
      bleeding 25 years after surgery and radiotherapy for seminoma of the testicle and
      was successfully treated at our institution. We also review the literature on
      this very uncommon condition. A Medline search was conducted for the period from
      1966 to June 2006 to identify case reports of PADF following radiotherapy. Only 7
      cases of PADF due to radiotherapy were identified in addition to our own, 4 males
      and 3 females, aged 40 to 73 years, all treated for various forms of abdominal
      malignancies. The latency period ranged from 2 weeks to 25 years. None of the
      aortas were aneurysmatic. One patient died before he could be taken to the
      operating room. 5 patients underwent surgical repair and 4 survived. 2 patients
      underwent endovascular treatment but did not survive. PADF may develop up to 25
      years after radiotherapy. Diagnosis should be considered when massive upper
      gastrointestinal bleeding develops in a patient who had previous abdominal
      radiotherapy, no matter how long before the episode of bleeding. Prompt surgical
      repair offers a reasonable chance of cure. Endovascular procedures do not appear
      to be efficacious.

PMID- 21897793
TI  - Spontaneous Resolution of Brain Edema in Fulminant Hepatic Failure due to
      Hepatitis E.
AB  - Fulminant hepatic failure is characterized by the presence of hepatic
      encephalopathy in the setting of acute liver injury that occurs in a noncirrhotic
      organ. Brain edema is the ultimate complication of advanced hepatic
      encephalopathy as it often leads to cerebral herniation and death. Thus, the
      presence of fulminant hepatic failure indicates the need for urgent liver
      transplantation to prevent death or irreversible brain damage. We report a very
      unusual evolution of fulminant hepatic failure complicated by brain edema and
      hepatic coma in a 45-year-old woman admitted with acute viral hepatitis E
      infection.

PMID- 21897794
TI  - Thirteen-year disease-free survival after surgery for cystic duct carcinoma: a
      case report.
AB  - Cystic duct carcinoma is known to have a better prognosis compared to its
      location in other biliary ducts. Only one case with a survival over ten years has
      been previously published. The authors report a case of survival over 13 years
      without recurrence or metastasis. Preoperative diagnosis of cystic duct tumor was
      carried in a 66-year-old male. Under the diagnosis of carcinoma of the cystic
      duct, the patient underwent en bloc resection of the gallbladder, cystic duct,
      hepaticocholedochus and lymph node dissection. A Roux-en-Y hepaticojejunostomy
      was performed. Histological examination revealed a moderately differentiated
      adenocarcinoma of the cystic duct. Five months later the patient underwent second
      look surgery for benign obstruction of the hepaticojejunal anastomosis. The
      patient is still doing well 13 years later without any local recurrence or
      metastasis. To our knowledge, this is the longest disease-free survival ever
      published in the literature. This case sustains that better and longer survival
      is possible with a real chance of potential cure if radical surgery is performed.

PMID- 21897795
TI  - Pancreatobiliary reflux resulting in pancreatic ascites and choleperitoneum after
      gallbladder perforation.
AB  - A 65-year-old man with chronic hepatitis C and no history of alcohol abuse was
      admitted to our liver unit for the recent development of massive ascites and
      presumed hepatorenal syndrome. In the preceding two weeks, he had received
      medical treatment for acute pancreatitis and cholecystitis. Abdominal
      paracentesis demonstrated a cloudy, orange peritoneal fluid, with total protein
      concentration 3.6 g/dl, serum-ascites albumin gradient 1.0 g/dl, and ratios of
      ascites-serum bilirubin and amylase approximately 8:1. Diagnostic imaging
      demonstrated no pancreatic pseudocysts. Ten days later, at laparotomy, acalculous
      perforation of the gallbladder was identified. After cholecystectomy, amylase
      concentration in the ascitic fluid dropped within a few days to 40% of serum
      values; ascites disappeared within a few weeks. We conclude that in the presence
      of a perforated gallbladder, pancreatobiliary reflux was responsible for this
      unusual combination of choleperitoneum and pancreatic ascites, which we propose
      to call pancreatobiliary ascites.

PMID- 21897796
TI  - Perforated hepatic hydatid cyst into the peritoneum with mild symptoms.
AB  - Rupture into the abdominal cavity is a rare but serious complication of hydatid
      disease that necessitates emergency surgical intervention. We present herein a
      case with mild abdominal symptoms due to hydatid cyst rupture into the peritoneum
      after trauma. A 24-year-old man was admitted to the emergency room with mild
      abdominal pain. His symptoms had started after a fall four days earlier.
      Ultrasonography and computed tomography showed cystic lesions in the liver and
      peritoneum with intraabdominal free fluid. He was treated surgically with partial
      cystectomy and falciformoplasty. Postoperative albendazole therapy was given for
      two months. There was not recurrence four months postoperatively at control
      computed tomography.

PMID- 21897797
TI  - Tuberculous duodenal stenosis: report of two cases.
AB  - Duodenal tuberculosis is a rare clinical entity. The authors report and emphasize
      the lack of special clinical, radiological and endoscopic signs of duodenal
      tuberculosis. The diagnosis is affirmed, at laparotomy, out of the findings of
      peritoneal granulations or histology of lymphatic nodes. We report our experience
      of two cases of duodenal tuberculosis presenting with proximal intestinal
      obstruction and review the available literature.

PMID- 21897798
TI  - Herpes simplex Virus Esophagitis in an Immunocompetent Patient with Ebstein-Barr
      Virus Infection.
AB  - Epstein-Barr virus infectious mononucleosis can cause transient immune deficiency
      which may predispose to reactivation of latent herpes simplex virus (HSV)
      infection in the immunocompetent host. We report the case of a 15-year-old male
      who presented with severe odynophagia and herpes labialis during the course of
      Epstein-Barr virus infectious mononucleosis that had been diagnosed ten days
      before. Esophagoscopy revealed extensive ulcerations with distinct borders and
      whitish exudates at the mid and distal esophagus. Polymerase chain reaction
      detected HSV-1 DNA in the biopsy specimens. The patient was treated with
      intravenous acyclovir. The symptoms resolved rapidly within 3 days, in accordance
      with improved endoscopic findings.

PMID- 21897799
TI  - Collision tumor of the stomach: a case of an adenocarcinoma and a
      gastrointestinal stromal tumor.
AB  - A collision tumor of the stomach is a rare event. We report the case of a
      collision tumor of the stomach consisting of an adenocarcinoma and a
      gastrointestinal stromal tumor (GIST). This is, to our knowledge, the second
      report in the literature of such a case. A 71-year-old man with abdominal
      discomfort underwent an esophagogastroduodenoscopy which revealed a tumor of the
      oesophagogastric junction. A total gastrectomy was performed. Histologic
      examination showed a mixed tumor consisting of a primary adenocarcinoma and
      multiple nodules of GIST. The adenocarcinoma showed both diffuse and intestinal
      growth, angio-invasion and metastasis to lymph nodes. The GIST tumor cells were
      strongly immunoreactive to CD117 and CD34. Based on mitotic index, size and
      cytonuclear details, the biological behavior of this GIST tumor was supposed to
      be benign. This case reports the rare finding of a collision tumor consisting of
      an adenocarcinoma and a GIST with an unknown etiology.

PMID- 21897800
TI  - Idiopathic myenteric ganglionitis underlying acute 'dramatic' intestinal
      pseudoobstruction: report of an exceptional case.
AB  - Inflammation of the myenteric plexus of the gastrointestinal tract is a very rare
      pathological condition, with few reports in the medical literature. This
      pathological condition causes atonic gut motor dysfunction and is principally
      secondary to other diseases, being reported nearly solely as a paraneoplastic
      phenomenon in neuroendocrine lung tumors, including small cell carcinomas or
      neuroblastomas. In addition it can also be associated with disorders of the
      central nervous system, although it has rarely been described in Chagas disease.
      It has been named 'idiopathic myenteric ganglionitis' because no apparent causes
      can be demonstrated. We report the clinicopathologic findings of an exceptional
      case of a young woman affected by severe chronic constipation suddenly changing
      into acute intestinal pseudoobstruction with dramatic evolution. Relationships
      between ganglionitis, idiopathic constipation and acute intestinal
      pseudoobstruction as well as therapeutic implications are discussed.

PMID- 21897801
TI  - Dieulafoy lesion in the stomach.
AB  - Dieulafoy disease is an uncommon cause of gastrointestinal system bleeding.
      Although the exact cause is not known, it is characterized by bleeding from
      abnormal submucosal vessels. There are many methods for diagnosis and treatment.
      In this case, a patient with a long-time undiagnosed stomach Dieulafoy lesion had
      a surgical resection. During the postoperative period the patient was discharged
      without any complication.

PMID- 21897802
TI  - Splenomegaly as a primary manifestation of Gaucher disease in a young adult
      woman.
AB  - Gaucher disease is the most common lysosomal storage disease. It is caused by the
      defective activity of acid beta-glucosidase, which results in the accumulation of
      lipid glucocerebroside in macrophages throughout the body. In this case report we
      describe the case of a young adult woman with splenomegaly as the primary
      manifestation of this pathology. This is a case of type 1 Gaucher disease because
      there is a lack of primary neurological involvement but we have, instead, an age
      independent involvement of the visceral organs. It is very important to classify
      or characterize these patients in a precise manner and to make a complete
      diagnosis with the help of the many diagnostic resources now at our disposal,
      especially with genetics, radiology and new techniques of advanced microscopy,
      also because Gaucher disease requires a long and complex management from early
      life to adulthood.

PMID- 21897803
TI  - Ciliated hepatic foregut cyst with obstructive jaundice.
AB  - Ciliated hepatic foregut cysts (CHFCs) are rare congenital cystic lesion that are
      most often solitary, unilocular, and located in the subcapsular region of the
      medial segment of the left hepatic lobe. The mucoid fluid contents affect imaging
      studies and often make definitive diagnosis difficult. CHFCs are usually
      asymptomatic and found incidentally. We report a 69-year-old female patient with
      a CHFC causing obstructive jaundice, which was difficult to differentiate from a
      biliary cystic neoplasm. A well-defined cystic lesion measuring 25 mm in diameter
      was located in the porta hepatis region. The lesion was densely adherent to the
      left and right hepatic ducts, riding on the bifurcation, and the common hepatic
      duct was extrinsically compressed. An extended left hepatectomy was performed. A
      diagnosis of CHFC was made on the basis of typical histological findings. CHFC
      should be included in the differential diagnosis for cystic lesions of the liver.

PMID- 21897804
TI  - Solid pseudopapillary tumor of the pancreas: an enigmatic tumor.
AB  - Solid pseudopapillary tumor of the pancreas is a rare pancreatic tumor that
      predominantly occurs in young non-Caucasian women. Although most tumors show
      benign behavior, malignant degeneration may occur. A case of solid
      pseudopapillary pancreatic tumor in a Caucasian woman is presented that was
      investigated by endoscopic ultrasonography (EUS), computed tomography, magnetic
      resonance imaging and EUS-guided fine needle aspiration. The patient underwent
      surgery and radiological findings are correlated with histopathology. The
      preoperative diagnosis of solid pseudopapillary tumor of the pancreas is
      challenging, frequently leading to imaging by multiple different modalities.

PMID- 21897805
TI  - Hemangiopericytoma in the small intestine: a case report.
AB  - Hemangiopericytoma is a rare tumor, mostly composed of pericytes of ramified
      appearance that are normally found all along the venules and capillaries. An 18
      year-old female was admitted on March 17, 1997 to the Department of Infectious
      Diseases for fever, chills and failure to thrive. Physical examination revealed a
      palpable tumorous mass in the iliac region on the right. The patient was
      transferred to the Department of Surgery. Vaginal examination and echotomography
      of the abdomen and pelvis minor were performed and revealed the presence of an
      irregular, inhomogeneous tumorous formation of 8 cm in diameter in the pelvis
      minor, differentially diagnostic right ovary, i.e. acute adnexitis or
      perityphlitic tumor. After that, small intestine resection, tumor excision in
      toto, and appendectomy were performed on April 16, 1997. Pathohistological
      diagnosis was hemangiopericytoma and chronic appendicitis. The biological
      behavior of this tumor is difficult to predict on the basis of clinical and
      morphological parameters. In our patient, local tumor excision was not followed
      by adjuvant therapy. After ten years, the patient is well, healthy and a mother
      of two healthy children.

PMID- 21897806
TI  - Esophagectomy in scleroderma: report of a case.
AB  - Scleroderma is a generalized autoimmune disease with variable involvement of the
      skin and major organs (esophagus, lung, heart and kidney). Scleroderma is
      essentially a skin disease that frequently involves the digestive system. In
      scleroderma, the esophagus is the most frequently affected organ of the digestive
      system, and esophageal dysmotility, reflux and stricture may be observed in the
      advanced stage. Balloon dilatation and bougienage are generally sufficient in
      patients developing stricture, and the number of cases in whom resection is
      performed is very low. In a 20-year-old patient with difficulty in taking even
      liquid foods, tests revealed sclerodermal involvement of the distal end of the
      esophagus and stricture. Esophageal resection and gastric replacement were
      performed. Such systemic diseases as scleroderma, although rare, must be
      considered in the differential diagnosis of nonmalignant dysphagia, and resection
      must be borne in mind as a surgical option in cases of advanced stricture.

PMID- 21897807
TI  - Chemotherapeutic treatment of priapism in metastatic rectal cancer.
AB  - A 65-year-old man was admitted with penile tenderness and dysuria due to
      priapism. Enhanced computed tomography revealed metastatic tumors in the liver,
      lung, sacrum and lymph nodes. Advanced rectal cancer, detected by colonoscopy as
      a primary tumor, was treated with chemotherapy (FOLFOX4). Although the rectal
      cancer showed no change, five months of chemotherapy improveid the priapism,
      suggesting that chemotherapy can improve rare symptoms of rectal cancer.

PMID- 21897808
TI  - Resovist-enhanced MRI for preoperative assessment of colorectal hepatic
      metastases: a case of multiple bile duct hamartomas associated with colon cancer.
AB  - Extensive preoperative assessment of hepatic metastases is required in colon
      cancer patients. We report a case in whom the preoperative investigation by
      ultrasound scan and contrast-enhanced computed tomography revealed numerous
      cystic lesions of the liver, suspicious of von Meyenburg complex. Magnetic
      resonance and magnetic resonance cholangiographic images demonstrated typical
      features of von Meyenburg complex. Further Resovist-enhanced magnetic resonance
      imaging detected two hemangiomas in addition to the multiple cystic lesions. So
      called Kupffer cell imaging strongly helped the detection of these hemangiomas,
      and a combination of various magnetic resonance pulse sequences was of great
      value for the differential diagnosis of cystic lesions and hemangiomas. In cases
      in whom conventional imaging studies fail to give a definite diagnosis, such as
      in the present case, superparamagnetic iron oxide-enhanced magnetic resonance
      imaging is meaningful for adequate preoperative staging.

PMID- 21897809
TI  - Delta Protocadherin 10 is Regulated by Activity in the Mouse Main Olfactory
      System.
AB  - Olfactory sensory neurons (OSNs) are thought to use activity-dependent and
      independent mechanisms to regulate the expression of axon guidance genes.
      However, defining the molecular mechanisms that underlie activity-dependent OSN
      guidance has remained elusive. Only a handful of genes have been identified whose
      expression is regulated by activity. Interestingly, all of these genes have been
      shown to play a role in OSN axon guidance, underscoring the importance of
      identifying other genes regulated by activity. Furthermore, studies suggest that
      more than one downstream mechanism regulates target gene expression. Thus, both
      the number of genes regulated by activity and how many total mechanisms control
      this expression are not well understood. Here we identify delta protocadherin 10
      (pcdh10) as a gene regulated by activity. Delta protocadherins are members of the
      cadherin superfamily, and pcdh10 is known to be important for axon guidance
      during development. We show pcdh10 is expressed in the nasal epithelium and
      olfactory bulb in patterns consistent with providing guidance information to
      OSNs. We use naris occlusion, genetic manipulations, and pharmacological assays
      to show pcdh10 can be regulated by activity, consistent with activation via the
      cyclic nucleotide-gated channel. Transgenic analysis confirms a potential role
      for pcdh10 in OSN axon guidance.

PMID- 21897810
TI  - Neuroglial plasticity at striatal glutamatergic synapses in Parkinson's disease.
AB  - Striatal dopamine denervation is the pathological hallmark of Parkinson's disease
      (PD). Another major pathological change described in animal models and PD
      patients is a significant reduction in the density of dendritic spines on medium
      spiny striatal projection neurons. Simultaneously, the ultrastructural features
      of the neuronal synaptic elements at the remaining corticostriatal and
      thalamostriatal glutamatergic axo-spinous synapses undergo complex
      ultrastructural remodeling consistent with increased synaptic activity (Villalba
      and Smith, 2011). The concept of tripartite synapses (TS) was introduced a decade
      ago, according to which astrocytes process and exchange information with neuronal
      synaptic elements at glutamatergic synapses (Araque et al., 1999a). Although
      there has been compelling evidence that astrocytes are integral functional
      elements of tripartite glutamatergic synaptic complexes in the cerebral cortex
      and hippocampus, their exact functional role, degree of plasticity and
      preponderance in other CNS regions remain poorly understood. In this review, we
      discuss our recent findings showing that neuronal elements at cortical and
      thalamic glutamatergic synapses undergo significant plastic changes in the
      striatum of MPTP-treated parkinsonian monkeys. We also present new
      ultrastructural data that demonstrate a significant expansion of the astrocytic
      coverage of striatal TS synapses in the parkinsonian state, providing further
      evidence for ultrastructural compensatory changes that affect both neuronal and
      glial elements at TS. Together with our limited understanding of the mechanisms
      by which astrocytes respond to changes in neuronal activity and extracellular
      transmitter homeostasis, the role of both neuronal and glial components of
      excitatory synapses must be considered, if one hopes to take advantage of glia
      neuronal communication knowledge to better understand the pathophysiology of
      striatal processing in parkinsonism, and develop new PD therapeutics.

PMID- 21897811
TI  - Top-down spatial categorization signal from prefrontal to posterior parietal
      cortex in the primate.
AB  - In the present study we characterized the strength and time course of category
      selective responses in prefrontal cortex and area 7a of the posterior parietal
      cortex during a match-to-sample spatial categorization task. A monkey was trained
      to categorize whether the height of a horizontal sample bar, presented in
      rectangular frame at one of three vertical locations, was "high" or "low,"
      depending on whether its position was above or below the frame's midline. After
      the display of this sample bar, and after a delay, choice bars were sequentially
      flashed in two locations: at the top and at the bottom of the frame ("choice"
      epoch). If the monkey timed its response to the display of the choice bar that
      matched the sample bar, he was rewarded. We found that cells in prefrontal cortex
      discriminated category early after the initial sample bar was shown, and
      continued to differentiate "up" from "down" trials throughout the delay and
      choice periods. In contrast, parietal cells did not differentiate category until
      the choice period. Therefore, our results support the notion of a top-down
      categorical signal that originates in prefrontal cortex and that is only
      represented in parietal cortex when it is necessary to express the categorical
      decision through a movement.

PMID- 21897812
TI  - The advantage of ambiguity? Enhanced neural responses to multi-stable percepts
      correlate with the degree of perceived instability.
AB  - Artwork can often pique the interest of the viewer or listener as a result of the
      ambiguity or instability contained within it. Our engagement with uncertain
      sensory experiences might have its origins in early cortical responses, in that
      perceptually unstable stimuli might preclude neural habituation and maintain
      activity in early sensory areas. To assess this idea, participants engaged with
      an ambiguous visual stimulus wherein two squares alternated with one another, in
      terms of simultaneously opposing vertical and horizontal locations relative to
      fixation (i.e., stroboscopic alternating motion; von Schiller, 1933). At each
      trial, participants were invited to interpret the movement of the squares in one
      of five ways: traditional vertical or horizontal motion, novel clockwise or
      counter-clockwise motion, and, a free-view condition in which participants were
      encouraged to switch the direction of motion as often as possible. Behavioral
      reports of perceptual stability showed clockwise and counter-clockwise motion to
      possess an intermediate level of stability compared to relatively stable vertical
      and horizontal motion, and, relatively unstable motion perceived during free-view
      conditions. Early visual evoked components recorded at parietal-occipital sites
      such as C1, P1, and N1 modulated as a function of visual intention. Both at a
      group and individual level, increased perceptual instability was related to
      increased negativity in all three of these early visual neural responses.
      Engagement with increasingly ambiguous input may partly result from the
      underlying exaggerated neural response to it. The study underscores the utility
      of combining neuroelectric recording with the presentation of perceptually multi
      stable yet physically identical stimuli, in revealing brain activity associated
      with the purely internal process of interpreting and appreciating the sensory
      world that surrounds us.

PMID- 21897813
TI  - Corticomotor Excitability during Observation and Imagination of a Work of Art.
AB  - We examine the effects of the artistic representation - here exemplified by
      Michelangelo's Expulsion from Paradise - of an action on the motor system. Using
      single and paired- pulse transcranial magnetic stimulation we analyze
      corticomotor excitability during observation of an action in the painting, during
      imagery of the painting, and during observation of a photograph of the same pose.
      We also analyze the effects of observation of two further paintings, one showing
      the same muscles at rest, and in the other in a more overtly emotional context.
      Both observation of the Expulsion and of imagery of the painting increased
      cortical excitability. Neither the relaxed pose of Michelangelo's Creation nor
      the flexed posture in the highly emotional context of Bellini's Dead Christ
      increased cortical excitability. Observation of a photograph of the same extended
      pose did not increase cortical excitability either. Moreover, intracortical
      inhibition was reduced during imagery of the painting. Our results offer clear
      motor correlates of the relationship between the esthetic quality of a work and
      the perception of implied movement within it.

PMID- 21897814
TI  - Distributed Patterns of Brain Activity that Lead to Forgetting.
AB  - Proactive interference (PI), in which irrelevant information from prior learning
      disrupts memory performance, is widely viewed as a major cause of forgetting.
      However, the hypothesized spontaneous recovery (i.e., automatic retrieval) of
      interfering information presumed to be at the base of PI remains to be
      demonstrated directly. Moreover, it remains unclear at what point during learning
      and/or retrieval interference impacts memory performance. In order to resolve
      these open questions, we employed a machine-learning algorithm to identify
      distributed patterns of brain activity associated with retrieval of interfering
      information that engenders PI and causes forgetting. Participants were scanned
      using functional magnetic resonance imaging during an item recognition task. We
      induced PI by constructing sets of three consecutive study lists from the same
      semantic category. The classifier quantified the magnitude of category-related
      activity at encoding and retrieval. Category-specific activity during retrieval
      increased across lists, consistent with the category information becoming
      increasingly available and producing interference. Critically, this increase was
      correlated with individual differences in forgetting and the deployment of
      frontal lobe mechanisms that resolve interference. Collectively, these findings
      suggest that distributed patterns of brain activity pertaining to the interfering
      information during retrieval contribute to forgetting. The prefrontal cortex
      mediates the relationship between the spontaneous recovery of interfering
      information at retrieval and individual differences in memory performance.

PMID- 21897815
TI  - Nipype: a flexible, lightweight and extensible neuroimaging data processing
      framework in python.
AB  - Current neuroimaging software offer users an incredible opportunity to analyze
      their data in different ways, with different underlying assumptions. Several
      sophisticated software packages (e.g., AFNI, BrainVoyager, FSL, FreeSurfer, Nipy,
      R, SPM) are used to process and analyze large and often diverse (highly multi
      dimensional) data. However, this heterogeneous collection of specialized
      applications creates several issues that hinder replicable, efficient, and
      optimal use of neuroimaging analysis approaches: (1) No uniform access to
      neuroimaging analysis software and usage information; (2) No framework for
      comparative algorithm development and dissemination; (3) Personnel turnover in
      laboratories often limits methodological continuity and training new personnel
      takes time; (4) Neuroimaging software packages do not address computational
      efficiency; and (5) Methods sections in journal articles are inadequate for
      reproducing results. To address these issues, we present Nipype (Neuroimaging in
      Python: Pipelines and Interfaces; http://nipy.org/nipype), an open-source,
      community-developed, software package, and scriptable library. Nipype solves the
      issues by providing Interfaces to existing neuroimaging software with uniform
      usage semantics and by facilitating interaction between these packages using
      Workflows. Nipype provides an environment that encourages interactive exploration
      of algorithms, eases the design of Workflows within and between packages, allows
      rapid comparative development of algorithms and reduces the learning curve
      necessary to use different packages. Nipype supports both local and remote
      execution on multi-core machines and clusters, without additional scripting.
      Nipype is Berkeley Software Distribution licensed, allowing anyone unrestricted
      usage. An open, community-driven development philosophy allows the software to
      quickly adapt and address the varied needs of the evolving neuroimaging
      community, especially in the context of increasing demand for reproducible
      research.

PMID- 21897816
TI  - Bivariate and Multivariate NeuroXidence: A Robust and Reliable Method to Detect
      Modulations of Spike-Spike Synchronization Across Experimental Conditions.
AB  - Synchronous neuronal firing has been proposed as a potential neuronal code. To
      determine whether synchronous firing is really involved in different forms of
      information processing, one needs to directly compare the amount of synchronous
      firing due to various factors, such as different experimental or behavioral
      conditions. In order to address this issue, we present an extended version of the
      previously published method, NeuroXidence. The improved method incorporates bi-
      and multivariate testing to determine whether different factors result in
      synchronous firing occurring above the chance level. We demonstrate through the
      use of simulated data sets that bi- and multivariate NeuroXidence reliably and
      robustly detects joint-spike-events across different factors.

PMID- 21897817
TI  - Two cases of unilateral ashy dermatosis.
AB  - Ashy dermatosis is a typically asymptomatic disease of unknown origin that causes
      symmetrical gray spots to appear on the trunk and extremities. We report 2 cases
      of ashy dermatosis with unilateral distribution. To our knowledge, only 5 cases
      of ashy dermatosis with unilateral lesion have been reported so far. Case 1: an
      11-year-old woman presented with asymptomatic slate-gray pigmented plaques on the
      left trunk and left upper arm. The skin biopsy specimen demonstrated a mild
      lymphohistiocytotic infiltrate in the upper dermis with epidermal and dermal
      melanosis. Q-Switched ruby laser did not improve such lesions. Case 2: a 21-year
      old man was referred to our hospital because of asymptomatic slate-gray pigmented
      plaques on the left trunk and left upper arm. Histopathological findings were
      compatible with a mild lymphocytic infiltration with melanin incontinence in the
      upper dermis. The mechanism that governs unilateral distribution of ashy
      dermatosis, including in our cases, remains unclear.

PMID- 21897818
TI  - The perils of a defective medical communication: fatal neglected squamous cell
      carcinoma arising in perineal hidradenitis suppurativa.
AB  - Hidradenitis suppurativa (HS) is a recurrent suppurative disease characterized by
      inflammatory nodules, abscesses, fistulas, and scarring. We report a case of
      squamous cell carcinoma arising in chronic HS. In our case the asymptomatic
      lesion was neglected by the patient for a long time, allowing the occurrence of
      advanced disease before treatment was sought, which resulted in a terminal
      outcome. In the context of HS, a painful lump or ulcer could easily be mistaken
      for an inflammatory lesion, and therefore a low threshold for biopsy is
      warranted.

PMID- 21897819
TI  - Stimulation of Wild-Type, F508del- and G551D-CFTR Chloride Channels by Non-Toxic
      Modified pyrrolo[2,3-b]pyrazine Derivatives.
AB  - Cystic fibrosis (CF) is a major inherited disorder involving abnormalities of
      fluid and electrolyte transport in a number of different organs due to abnormal
      function of cystic fibrosis transmembrane conductance regulator (CFTR) protein.
      We recently identified a family of CFTR activators, which contains the hit: RP107
      [7-n-butyl-6-(4-hydroxyphenyl)[5H]-pyrrolo[2,3-b]pyrazine]. Here, we further
      evaluated the effect of the chemical modifications of the RP107-OH radical on
      CFTR activation. The replacement of the OH radical by a fluorine atom at position
      2 (RP193) or 4 (RP185) significantly decreased the toxicity of the compounds
      without altering the ability to activate CFTR, especially for RP193. The non
      toxic compound RP193 has no effect on cAMP production but stimulates the channel
      activity of wild-type CFTR in stably transfected CHO cells, in human bronchial
      epithelial NuLi-1 cells, and in primary culture of human bronchial epithelial
      cells (HBEC). Whole-cell and single patch-clamp recordings showed that RP193
      induced a linear, time- and voltage-independent current, which was fully
      inhibited by two different and selective CFTR inhibitors (CFTRinh-172 and
      GP(inh)5a). Moreover, RP193 stimulates CFTR in temperature-rescued CuFi-1
      (F508del/F508del) HBEC and in CHO cells stably expressing G551D-CFTR. This study
      shows that it is feasible to reduce cytotoxicity of chemical compounds without
      affecting their potency to activate CFTR and to rescue the class 2 F508del-CFTR
      and class 3 G551D-CFTR CF mutant activities.

PMID- 21897820
TI  - Lessons Learnt from Post-Infectious IBS.
AB  - The development of IBS symptoms - altered bowel function and abdominal cramping
      in a subset of adult subjects exposed to severe enteric infections opened up an
      unprecedented opportunity to understand the etiology of this poorly understood
      disorder. Perhaps, for the reasons that these symptoms follow a severe enteric
      infection, and mucosal biopsy tissues are readily available, the focus of most
      studies thus far has been to show that mild/low-grade mucosal inflammation
      persisting after the initial infection has subsided causes the IBS symptoms.
      Parallel studies in non-infectious IBS patients, who did not have prior
      enteritis, showed similar mild mucosal inflammation. Together, these studies
      examined the mucosal infiltration of specific immune cells, increase of select
      inflammatory mediators, mast cell and enterochromaffin cell hyperplasia, and
      epithelial permeability. In spite of the fact that the data on these topics were
      not consistent among different studies and clinical trials with prednisone,
      fluoxetine, and ketotifen failed to provide relief of IBS symptoms, the
      predominant conclusions were that mild mucosal inflammation is the cause of IBS
      symptoms. However, the circular smooth muscle cells, and myenteric neurons are
      the primary regulators of gut motility function, while primary afferent neurons
      and CNS play essential roles in induction of visceral hypersensitivity - no
      explanation was provided as to how mild mucosal inflammation causes dysfunction
      in cells far removed. Accumulating evidence shows that mild mucosal inflammation
      in IBS patients is in physiological range. It has little deleterious effects on
      cells within its own environment and therefore it is unlikely to affect cells in
      the muscularis externa. This review discusses the disconnect between the focus on
      mild/low-grade mucosal inflammation and the potential mechanisms and molecular
      dysfunctions in smooth muscle cells, myenteric neurons, and primary afferent
      neurons that may underlie IBS symptoms.

PMID- 21897821
TI  - The role of aquaporins in the kidney of euryhaline teleosts.
AB  - WATER BALANCE IN TELEOST FISH IS MAINTAINED WITH CONTRIBUTIONS FROM THE MAJOR
      OSMOREGULATORY ORGANS: intestine, gills, and kidney. Overall water fluxes have
      been studied in all of these organs but not until recently has it become possible
      to approach the mechanisms of water transport at the molecular level. This mini
      review addresses the role of the kidney in osmoregulation with special emphasis
      on euryhaline teleosts. After a short review of current knowledge of renal
      functional morphology and regulation, we turn the focus to recent molecular
      investigations of the role of aquaporins in water and solute transport in the
      teleost kidney. We conclude that there is much to be achieved in understanding
      water transport and its regulation in the teleost kidney and that effort should
      be put into systematic mapping of aquaporins to their tubular as well as cellular
      localization.

PMID- 21897823
TI  - Detailed sensory memory, sloppy working memory.
AB  - Visual short-term memory (VSTM) enables us to actively maintain information in
      mind for a brief period of time after stimulus disappearance. According to recent
      studies, VSTM consists of three stages - iconic memory, fragile VSTM, and visual
      working memory - with increasingly stricter capacity limits and progressively
      longer lifetimes. Still, the resolution (or amount of visual detail) of each VSTM
      stage has remained unexplored and we test this in the present study. We presented
      people with a change detection task that measures the capacity of all three forms
      of VSTM, and we added an identification display after each change trial that
      required people to identify the "pre-change" object. Accurate change detection
      plus pre-change identification requires subjects to have a high-resolution
      representation of the "pre-change" object, whereas change detection or
      identification only can be based on the hunch that something has changed, without
      exactly knowing what was presented before. We observed that people maintained 6.1
      objects in iconic memory, 4.6 objects in fragile VSTM, and 2.1 objects in visual
      working memory. Moreover, when people detected the change, they could also
      identify the pre-change object on 88% of the iconic memory trials, on 71% of the
      fragile VSTM trials and merely on 53% of the visual working memory trials. This
      suggests that people maintain many high-resolution representations in iconic
      memory and fragile VSTM, but only one high-resolution object representation in
      visual working memory.

PMID- 21897822
TI  - Mental imagery of speech and movement implicates the dynamics of internal forward
      models.
AB  - The classical concept of efference copies in the context of internal forward
      models has stimulated productive research in cognitive science and neuroscience.
      There are compelling reasons to argue for such a mechanism, but finding direct
      evidence in the human brain remains difficult. Here we investigate the dynamics
      of internal forward models from an unconventional angle: mental imagery, assessed
      while recording high temporal resolution neuronal activity using
      magnetoencephalography. We compare two overt and covert tasks; our covert, mental
      imagery tasks are unconfounded by overt input/output demands - but in turn
      necessitate the development of appropriate multi-dimensional topographic
      analyses. Finger tapping (studies 1 and 2) and speech experiments (studies 3-5)
      provide temporally constrained results that implicate the estimation of an
      efference copy. We suggest that one internal forward model over parietal cortex
      subserves the kinesthetic feeling in motor imagery. Secondly, observed auditory
      neural activity ~170 ms after motor estimation in speech experiments (studies 3
      5) demonstrates the anticipated auditory consequences of planned motor commands
      in a second internal forward model in imagery of speech production. Our results
      provide neurophysiological evidence from the human brain in favor of internal
      forward models deploying efference copies in somatosensory and auditory cortex,
      in finger tapping and speech production tasks, respectively, and also suggest the
      dynamics and sequential updating structure of internal forward models.

PMID- 21897824
TI  - Does Area V3A Predict Positions of Moving Objects?
AB  - A gradually fading moving object is perceived to disappear at positions beyond
      its luminance detection threshold, whereas abrupt offsets are usually localized
      accurately. What role does retinotopic activity in visual cortex play in this
      motion-induced mislocalization of the endpoint of fading objects? Using
      functional magnetic resonance imaging (fMRI), we localized regions of interest
      (ROIs) in retinotopic maps abutting the trajectory endpoint of a bar moving
      either toward or away from this position while gradually decreasing or increasing
      in luminance. Area V3A showed predictive activity, with stronger fMRI responses
      for motion toward versus away from the ROI. This effect was independent of the
      change in luminance. In Area V1 we found higher activity for high-contrast onsets
      and offsets near the ROI, but no significant differences between motion
      directions. We suggest that perceived final positions of moving objects are based
      on an interplay of predictive position representations in higher motion-sensitive
      retinotopic areas and offset transients in primary visual cortex.

PMID- 21897825
TI  - The forager oral tradition and the evolution of prolonged juvenility.
AB  - The foraging niche is characterized by the exploitation of nutrient-rich
      resources using complex extraction techniques that take a long time to acquire.
      This costly period of development is supported by intensive parental investment.
      Although human life history theory tends to characterize this investment in terms
      of food and care, ethnographic research on foraging skill transmission suggests
      that the flow of resources from old-to-young also includes knowledge. Given the
      adaptive value of information, parents may have been under selection pressure to
      invest knowledge - e.g., warnings, advice - in children: proactive provisioning
      of reliable information would have increased offspring survival rates and, hence,
      parental fitness. One way that foragers acquire subsistence knowledge is through
      symbolic communication, including narrative. Tellingly, oral traditions are
      characterized by an old-to-young transmission pattern, which suggests that, in
      forager groups, storytelling might be an important means by which adults transfer
      knowledge to juveniles. In particular, by providing juveniles with vicarious
      experience, storytelling may expand episodic memory, which is believed to be
      integral to the generation of possible future scenarios (i.e., planning). In
      support of this hypothesis, this essay reviews evidence that: mastery of foraging
      knowledge and skill sets takes a long time to acquire; foraging knowledge is
      transmitted from parent to child; the human mind contains adaptations specific to
      social learning; full assembly of learning mechanisms is not complete in early
      childhood; and forager oral traditions contain a wide range of information
      integral to occupation of the foraging niche. It concludes with suggestions for
      tests of the proposed hypothesis.

PMID- 21897826
TI  - Strength gains by motor imagery with different ratios of physical to mental
      practice.
AB  - The purpose of this training study was to determine the magnitude of strength
      gains following a high-intensity resistance training (i.e., improvement of
      neuromuscular coordination) that can be achieved by imagery of the respective
      muscle contraction imagined maximal isometric contraction (IMC training). Prior
      to the experimental intervention, subjects completed a 4-week standardized
      strength training program. 3 groups with different combinations of real maximum
      voluntary contraction (MVC) and mental (IMC) strength training (M75, M50, M25;
      numbers indicate percentages of mental trials) were compared to a MVC-only
      training group (M0) and a control condition without strength training (CO).
      Training sessions (altogether 12) consisted of four sets of two maximal 5-s
      isometric contractions with 10 s rest between sets of either MVC or IMC training.
      Task-specific effects of IMC training were tested in four strength exercises
      commonly used in practical settings (bench pressing, leg pressing, triceps
      extension, and calf raising). Maximum isometric voluntary contraction force (MVC)
      was measured before and after the experimental training intervention and again 1
      week after cessation of the program. IMC groups (M25, M50, M75) showed slightly
      smaller increases in MVC (3.0% to 4.2%) than M0 (5.1%), but significantly
      stronger improvements than CO (-0.2%). Compared to further strength gains in M0
      after 1 week (9.4% altogether), IMC groups showed no "delayed" improvement, but
      the attained training effects remained stable. It is concluded that high
      intensity strength training sessions can be partly replaced by IMC training
      sessions without any considerable reduction of strength gains.

PMID- 21897827
TI  - Intercepting the First Pass: Rapid Categorization is Suppressed for Unseen
      Stimuli.
AB  - The operations and processes that the human brain employs to achieve fast visual
      categorization remain a matter of debate. A first issue concerns the timing and
      place of rapid visual categorization and to what extent it can be performed with
      an early feed-forward pass of information through the visual system. A second
      issue involves the categorization of stimuli that do not reach visual awareness.
      There is disagreement over the degree to which these stimuli activate the same
      early mechanisms as stimuli that are consciously perceived. We employed
      continuous flash suppression (CFS), EEG recordings, and machine learning
      techniques to study visual categorization of seen and unseen stimuli. Our
      classifiers were able to predict from the EEG recordings the category of stimuli
      on seen trials but not on unseen trials. Rapid categorization of conscious images
      could be detected around 100 ms on the occipital electrodes, consistent with a
      fast, feed-forward mechanism of target detection. For the invisible stimuli,
      however, CFS eliminated all traces of early processing. Our results support the
      idea of a fast mechanism of categorization and suggest that this early
      categorization process plays an important role in later, more subtle
      categorizations, and perceptual processes.

PMID- 21897828
TI  - Initial experience with the coaxial dual-lumen ascent balloon catheter for wide
      neck aneurysm coil embolization.
AB  - INTRODUCTION: Techniques for coil embolization of wide-neck cerebral aneurysms
      include the use of stents and temporary occlusion with compliant non-detachable
      balloons to safely allow dense packing of the aneurysm lumen with detachable
      coils. We describe the use of a new balloon device for assisting in wide-neck
      aneurysm coil treatment. METHODS: A single institution neuroendovascular database
      was accessed to identify cases in which the Ascent balloon (Codman Neurovascular,
      Raynham, MA, USA) was used for aneurysm coil embolization. Clinical, demographic,
      and angiographic data were obtained through chart review. RESULTS: Eleven
      cerebral aneurysm cases were treated using the Ascent balloon during the first 12
      month period that the new device was available at our institution. Three of the
      patients presented with ruptured aneurysms. All aneurysms were large (maximum
      diameter 6 mm or greater), with an average maximum diameter of 9.4 mm, and an
      average neck diameter of 5.5 mm. Complete occlusion with coil embolization
      (Raymond class I) was achieved in all cases. The Ascent balloon was successfully
      positioned across the neck of the aneurysm in nine patients. CONCLUSION: This
      initial experience demonstrates the feasibility and immediate outcomes of the
      coaxial dual-lumen design Ascent balloon catheter used as an assistive device in
      coil embolization of wide-neck cerebral aneurysms. This device contributes to the
      growing number of assistive devices for the treatment of complex cerebral
      aneurysms.

PMID- 21897829
TI  - 'They don't understand...you cut yourself in order to live.' Interpretative
      repertoires jointly constructing interactions between adult women who self-harm
      and professional caregivers.
AB  - The aim of the study was to illuminate interpretative repertoires that jointly
      construct the interaction between adult women who self-harm and professional
      caregivers in psychiatric inpatient care. Participant observations and informal
      interviews were conducted among six women who self-harm and their professional
      caregivers in two psychiatric inpatient wards, and analysed using the concept of
      interpretative repertoires from the discipline of discursive psychology. The
      analysis revealed four interpretative repertoires that jointly constructed the
      interaction. The professional caregivers used a "fostering repertoire" and a
      "supportive repertoire" and the women who self-harmed used a "victim repertoire"
      and an "expert repertoire." The women and the caregivers were positioned and
      positioned themselves and people around them within and among these
      interpretative repertoires to make sense of their experiences of the interaction.
      It was necessary to consider each woman's own life chances and knowledge about
      herself and her needs. The participants made it clear that it was essential for
      them to be met with respect as individuals. Professional caregivers need to work
      in partnership with individuals who self-harm-experts by profession collaborating
      with experts by experience. Caregivers need to look beyond behavioural symptoms
      and recognise each individual's possibilities for agency.

PMID- 21897830
TI  - Children's understandings' of obesity, a thematic analysis.
AB  - Childhood obesity is a major concern in today's society. Research suggests the
      inclusion of the views and understandings of a target group facilitates
      strategies that have better efficacy. The objective of this study was to explore
      the concepts and themes that make up children's understandings of the causes and
      consequences of obesity. Participants were selected from Reception (4-5 years
      old) and Year 6 (10-11 years old), and attended a school in an area of
      Sunderland, in North East England. Participants were separated according to age
      and gender, resulting in four focus groups, run across two sessions. A thematic
      analysis (Braun & Clarke, 2006) identified overarching themes evident across all
      groups, suggesting the key concepts that contribute to children's understandings
      of obesity are "Knowledge through Education," "Role Models," "Fat is Bad," and
      "Mixed Messages." The implications of these findings and considerations of the
      methodology are discussed in full.

PMID- 21897831
TI  - A case of Kawasaki disease with anasarca and concomitant rotavirus infection.
AB  - We present the case of a child who initially presented with gastrointestinal
      symptoms suggestive of severe rotavirus gastroenteritis complicated by
      hyponatraemic dehydration. Appropriate intravenous fluid therapy was administered
      but the patient, still feverish, developed anasarca probably due to
      hyperpermeability of microvessels following massive inflammation. Atypical
      Kawasaki disease was diagnosed on the basis of the clinical findings and
      laboratory tests. An echocardiogram performed on the 14th day showed a coronary
      artery aneurysm of the right coronary artery and a generalised dilation of left
      coronary artery without pericardial effusion. Anasarca in Kawasaki disease has
      never been reported before in the literature. A rotavirus infection probably
      triggered the severe and atypical signs in the case reported here.

PMID- 21897832
TI  - Bronchial associated lymphoid tissue (BALT) lymphoma presenting as chronic lung
      sepsis.
AB  - A 58-year-old woman was referred from her general practitioner to the respiratory
      clinic with a 2 year history of recurrent pulmonary infections, mucus
      hypersecretion and right lobe consolidation following a severe pneumonic illness
      in 2006. She had no significant risk factors for respiratory disease. Chest
      computed tomography showed an air bronchogram and right lower lobe consolidation.
      On initial routine investigation IgA and IgG were normal; however, a discrete IgM
      paraprotein band in the mid gamma region was seen on serum electrophoresis. She
      was referred for haematological investigations. Bone marrow biopsy was positive
      for monoclonal lymphoplasmocytoid B cells and the patient was diagnosed with
      Waldenstrom's macroglobulinaemia. Due to recurrent infections and an unclear
      diagnosis of the lung process, a right lower lobectomy and wedge resection of the
      middle lobe was performed. This showed bronchial associated lymphoid tissue
      lymphoma arising in the marginal zone. She has been well since surgery with no
      further respiratory infections.

PMID- 21897833
TI  - Chronic urticaria as a presenting symptom of Crohn's disease.
AB  - Clinical presentation of Crohn's disease (CD) may be variable according to the
      location and the intensity of the inflammation. Some patients may have atypical
      symptoms which could delay the diagnosis. We report the first case of chronic
      urticaria related to a subclinical, complicated CD. Although the pathologic
      mechanism of this association was unclear in our patient, this case suggests that
      in patients with unexplained chronic urticaria it is opportune to investigate for
      a possible CD, even if there are no or few specific symptoms of intestinal
      inflammatory disease.

PMID- 21897834
TI  - Congenital tuberculosis in premature twins after in vitro fertilisation.
AB  - Genital tuberculosis is a major cause of infertility in countries where
      tuberculosis is endemic. With recent advances in assisted reproductive
      technology, women with tuberculous endometritis may become pregnant and
      ultimately have children with congenital tuberculosis. In vitro fertilisation
      represents a useful treatment for infertility. Congenital tuberculosis is a rare
      and severe, rapidly progressive, disease. Making an early diagnosis of congenital
      tuberculosis is difficult, because it can mimic many neonatal illnesses. To the
      best of our knowledge, we report the first cases of premature twins with
      congenital tuberculosis following in vitro fertilisation. After the diagnosis of
      genital tuberculosis in the mother, the twins were screened and diagnosed for
      tuberculosis. The twins dramatically improved after anti-tuberculosis therapy. We
      also wish to draw attention to the importance of searching for genital
      tuberculosis as the possible cause of congenital infection, even if the mother is
      asymptomatic.

PMID- 21897835
TI  - Remodelling of coronary arteries.

PMID- 21897836
TI  - Concomitant tuberculosis and hydatid cyst in a solitary pulmonary nodule of left
      lower lobe.
AB  - We report a case of a 25-year-old woman who presented with recurrent attacks of
      haemoptysis over a 12 month period. Physical examination was normal. Chest x ray
      and computed tomography scan showed a 2.6*1.9 cm pulmonary nodule. Full blood
      count and biochemical profile were normal. Fibreoptic bronchoscopy was normal and
      bronchial aspirate was negative for Ziehl-Neelsen staining and malignant cells.
      The nodule was removed surgically because it was feared that it could be
      malignant. Histology showed concomitant hydatid disease and tuberculosis. This is
      a rare occurrence with only one similar case reported in the literature.

PMID- 21897837
TI  - Sensory grammars for sensor networks.
AB  - One of the major goals of Ambient Intelligence and Smart Environments is to
      interpret human activity sensed by a variety of sensors. In order to develop
      useful technologies and a subsequent industry around smart environments, we need
      to proceed in a principled manner. This paper suggests that human activity can be
      expressed in a language. This is a special language with its own phonemes, its
      own morphemes (words) and its own syntax and it can be learned using machine
      learning techniques applied to gargantuan amounts of data collected by sensor
      networks. Developing such languages will create bridges between Ambient
      Intelligence and other disciplines. It will also provide a hierarchical structure
      that can lead to a successful industry.

PMID- 21897838
TI  - Parasite transmission in social interacting hosts: monogenean epidemics in
      guppies.
AB  - BACKGROUND: Infection incidence increases with the average number of contacts
      between susceptible and infected individuals. Contact rates are normally assumed
      to increase linearly with host density. However, social species seek out each
      other at low density and saturate their contact rates at high densities. Although
      predicting epidemic behaviour requires knowing how contact rates scale with host
      density, few empirical studies have investigated the effect of host density.
      Also, most theory assumes each host has an equal probability of transmitting
      parasites, even though individual parasite load and infection duration can vary.
      To our knowledge, the relative importance of characteristics of the primary
      infected host vs. the susceptible population has never been tested
      experimentally. METHODOLOGY/PRINCIPAL FINDINGS: Here, we examine epidemics using
      a common ectoparasite, Gyrodactylus turnbulli infecting its guppy host (Poecilia
      reticulata). Hosts were maintained at different densities (3, 6, 12 and 24 fish
      in 40 L aquaria), and we monitored gyrodactylids both at a population and
      individual host level. Although parasite population size increased with host
      density, the probability of an epidemic did not. Epidemics were more likely when
      the primary infected fish had a high mean intensity and duration of infection.
      Epidemics only occurred if the primary infected host experienced more than 23
      worm days. Female guppies contracted infections sooner than males, probably
      because females have a higher propensity for shoaling. CONCLUSIONS/SIGNIFICANCE:
      These findings suggest that in social hosts like guppies, the frequency of social
      contact largely governs disease epidemics independent of host density.

PMID- 21897839
TI  - The microRNA-200 family is upregulated in endometrial carcinoma.
AB  - BACKGROUND: MicroRNAs (miRNAs, miRs) are small non-coding RNAs that negatively
      regulate gene expression at the post-transcriptional level. MicroRNAs are
      dysregulated in cancer and may play essential roles in tumorigenesis.
      Additionally, miRNAs have been shown to have prognostic and diagnostic value in
      certain types of cancer. The objective of this study was to identify dysregulated
      miRNAs in endometrioid endometrial adenocarcinoma (EEC) and the precursor lesion,
      complex atypical hyperplasia (CAH). METHODOLOGY: We compared the expression
      profiles of 723 human miRNAs from 14 cases of EEC, 10 cases of CAH, and 10 normal
      proliferative endometria controls using Agilent Human miRNA arrays following RNA
      extraction from formalin-fixed paraffin-embedded (FFPE) tissues. The expression
      of 4 dysregulated miRNAs was validated using real time reverse transcription-PCR.
      RESULTS: Forty-three miRNAs were dysregulated in EEC and CAH compared to normal
      controls (p<0.05). The entire miR-200 family (miR-200a/b/c, miR-141, and miR-429)
      was up-regulated in cases of EEC. CONCLUSIONS: This information contributes to
      the candidate miRNA expression profile that has been generated for EEC and shows
      that certain miRNAs are dysregulated in the precursor lesion, CAH. These miRNAs
      in particular may play important roles in tumorigenesis. Examination of miRNAs
      that are consistently dysregulated in various studies of EEC, like the miR-200
      family, will aid in the understanding of the role that miRNAs play in
      tumorigenesis in this tumour type.

PMID- 21897840
TI  - Facilitating tumor functional assessment by spatially relating 3D tumor histology
      and in vivo MRI: image registration approach.
AB  - BACKGROUND: Magnetic resonance imaging (MRI), together with histology, is widely
      used to diagnose and to monitor treatment in oncology. Spatial correspondence
      between these modalities provides information about the ability of MRI to
      characterize cancerous tissue. However, registration is complicated by
      deformations during pathological processing, and differences in scale and
      information content. METHODOLOGY/PRINCIPAL FINDINGS: This study proposes a
      methodology for establishing an accurate 3D relation between histological
      sections and high resolution in vivo MRI tumor data. The key features of the
      methodology are: 1) standardized acquisition and processing, 2) use of an
      intermediate ex vivo MRI, 3) use of a reference cutting plane, 4) dense
      histological sampling, 5) elastic registration, and 6) use of complete 3D data
      sets. Five rat pancreatic tumors imaged by T2*-w MRI were used to evaluate the
      proposed methodology. The registration accuracy was assessed by root mean squared
      (RMS) distances between manually annotated landmark points in both modalities.
      After elastic registration the average RMS distance decreased from 1.4 to 0.7 mm.
      The intermediate ex vivo MRI and the reference cutting plane shared by all three
      3D images (in vivo MRI, ex vivo MRI, and 3D histology data) were found to be
      crucial for the accurate co-registration between the 3D histological data set and
      in vivo MRI. The MR intensity in necrotic regions, as manually annotated in 3D
      histology, was significantly different from other histologically confirmed
      regions (i.e., viable and hemorrhagic). However, the viable and the hemorrhagic
      regions showed a large overlap in T2(*)-w MRI signal intensity. CONCLUSIONS: The
      established 3D correspondence between tumor histology and in vivo MRI enables
      extraction of MRI characteristics for histologically confirmed regions. The
      proposed methodology allows the creation of a tumor database of spatially
      registered multi-spectral MR images and multi-stained 3D histology.

PMID- 21897841
TI  - Randomised controlled feasibility trial of an evidence-informed behavioural
      intervention for obese adults with additional risk factors.
AB  - BACKGROUND: Interventions for dietary and physical activity changes in obese
      adults may be less effective for participants with additional obesity-related
      risk factors and co-morbidities than for otherwise healthy individuals. This
      study aimed to test the feasibility and acceptability of the recruitment,
      allocation, measurement, retention and intervention procedures of a randomised
      controlled trial of an intervention to improve physical activity and dietary
      practices amongst obese adults with additional obesity related risk factors.
      METHOD: Pilot single centre open-labelled outcome assessor-blinded randomised
      controlled trial of obese (Body Mass Index (BMI)>=30 kg/m2) adults (age>=18 y)
      with obesity related co-morbidities such as type 2 diabetes, impaired glucose
      tolerance or hypertension. Participants were randomly allocated to a manual-based
      group intervention or a leaflet control condition in accordance to a 2?1
      allocation ratio. Primary outcome was acceptability and feasibility of trial
      procedures, secondary outcomes included measures of body composition, physical
      activity, food intake and psychological process measures. RESULTS: Out of 806
      potentially eligible individuals identified through list searches in two primary
      care general medical practices N = 81 participants (63% female; mean-age =
      56.56(11.44); mean-BMI = 36.73(6.06)) with 2.35(1.47) co-morbidities were
      randomised. Scottish Index of Multiple Deprivation (SIMD) was the only
      significant predictor of providing consent to take part in the study (higher
      chances of consent for invitees with lower levels of deprivation). Participant
      flowcharts, qualitative and quantitative feedback suggested good acceptance and
      feasibility of intervention procedures but 34.6% of randomised participants were
      lost to follow-up due to overly high measurement burden and sub-optimal retention
      procedures. Participants in the intervention group showed positive trends for
      most psychological, behavioural and body composition outcomes. CONCLUSIONS: The
      intervention procedures were found to be acceptable and feasible. Attrition rates
      were unacceptably high and areas for improvements of trial procedures were
      identified. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN90101501.

PMID- 21897842
TI  - Spiking patterns and their functional implications in the antennal lobe of the
      tobacco hornworm Manduca sexta.
AB  - Bursting as well as tonic firing patterns have been described in various sensory
      systems. In the olfactory system, spontaneous bursts have been observed in
      neurons distributed across several synaptic levels, from the periphery, to the
      olfactory bulb (OB) and to the olfactory cortex. Several in vitro studies
      indicate that spontaneous firing patterns may be viewed as "fingerprints" of
      different types of neurons that exhibit distinct functions in the OB. It is still
      not known, however, if and how neuronal burstiness is correlated with the coding
      of natural olfactory stimuli. We thus conducted an in vivo study to probe this
      question in the OB equivalent structure of insects, the antennal lobe (AL) of the
      tobacco hornworm Manduca sexta. We found that in the moth's AL, both projection
      (output) neurons (PNs) and local interneurons (LNs) are spontaneously active, but
      PNs tend to produce spike bursts while LNs fire more regularly. In addition, we
      found that the burstiness of PNs is correlated with the strength of their
      responses to odor stimulation--the more bursting the stronger their responses to
      odors. Moreover, the burstiness of PNs was also positively correlated with the
      spontaneous firing rate of these neurons, and pharmacological reduction of
      bursting resulted in a decrease of the neurons' responsiveness. These results
      suggest that neuronal burstiness reflects a physiological state of these neurons
      that is directly linked to their response characteristics.

PMID- 21897843
TI  - Enhanced osteoclastic resorption and responsiveness to mechanical load in gap
      junction deficient bone.
AB  - Emerging evidence suggests that connexin mediated gap junctional intercellular
      communication contributes to many aspects of bone biology including bone
      development, maintenance of bone homeostasis and responsiveness of bone cells to
      diverse extracellular signals. Deletion of connexin 43, the predominant gap
      junction protein in bone, is embryonic lethal making it challenging to examine
      the role of connexin 43 in bone in vivo. However, transgenic murine models in
      which only osteocytes and osteoblasts are deficient in connexin 43, and which are
      fully viable, have recently been developed. Unfortunately, the bone phenotype of
      different connexin 43 deficient models has been variable. To address this issue,
      we used an osteocalcin driven Cre-lox system to create osteoblast and osteocyte
      specific connexin 43 deficient mice. These mice displayed bone loss as a result
      of increased bone resorption and osteoclastogenesis. The mechanism underlying
      this increased osteoclastogenesis included increases in the osteocytic, but not
      osteoblastic, RANKL/OPG ratio. Previous in vitro studies suggest that connexin 43
      deficient bone cells are less responsive to biomechanical signals. Interestingly,
      and in contrast to in vitro studies, we found that connexin 43 deficient mice
      displayed an enhanced anabolic response to mechanical load. Our results suggest
      that transient inhibition of connexin 43 expression and gap junctional
      intercellular communication may prove a potentially powerful means of enhancing
      the anabolic response of bone to mechanical loading.

PMID- 21897844
TI  - Identification and visualization of CD8+ T cell mediated IFN-gamma signaling in
      target cells during an antiviral immune response in the brain.
AB  - CD8(+) T cells infiltrate the brain during an anti-viral immune response. Within
      the brain CD8(+) T cells recognize cells expressing target antigens, become
      activated, and secrete IFNgamma. However, there are no methods to recognize
      individual cells that respond to IFNgamma. Using a model that studies the effects
      of the systemic anti-adenoviral immune response upon brain cells infected with an
      adenoviral vector in mice, we describe a method that identifies individual cells
      that respond to IFNgamma. To identify individual mouse brain cells that respond
      to IFNgamma we constructed a series of adenoviral vectors that contain a
      transcriptional response element that is selectively activated by IFNgamma
      signaling, the gamma-activated site (GAS) promoter element; the GAS element
      drives expression of a transgene, Cre recombinase (Ad-GAS-Cre). Upon binding of
      IFNgamma to its receptor, the intracellular signaling cascade activates the GAS
      promoter, which drives expression of the transgene Cre recombinase. We
      demonstrate that upon activation of a systemic immune response against
      adenovirus, CD8(+) T cells infiltrate the brain, interact with target cells, and
      cause an increase in the number of cells expressing Cre recombinase. This method
      can be used to identify, study, and eventually determine the long term fate of
      infected brain cells that are specifically targeted by IFNgamma. The significance
      of this method is that it will allow to characterize the networks in the brain
      that respond to the specific secretion of IFNgamma by anti-viral CD8(+) T cells
      that infiltrate the brain. This will allow novel insights into the cellular and
      molecular responses underlying brain immune responses.

PMID- 21897845
TI  - Germline transgenic pigs by Sleeping Beauty transposition in porcine zygotes and
      targeted integration in the pig genome.
AB  - Genetic engineering can expand the utility of pigs for modeling human diseases,
      and for developing advanced therapeutic approaches. However, the inefficient
      production of transgenic pigs represents a technological bottleneck. Here, we
      assessed the hyperactive Sleeping Beauty (SB100X) transposon system for enzyme
      catalyzed transgene integration into the embryonic porcine genome. The components
      of the transposon vector system were microinjected as circular plasmids into the
      cytoplasm of porcine zygotes, resulting in high frequencies of transgenic fetuses
      and piglets. The transgenic animals showed normal development and persistent
      reporter gene expression for >12 months. Molecular hallmarks of transposition
      were confirmed by analysis of 25 genomic insertion sites. We demonstrate germ
      line transmission, segregation of individual transposons, and continued, copy
      number-dependent transgene expression in F1-offspring. In addition, we
      demonstrate target-selected gene insertion into transposon-tagged genomic loci by
      Cre-loxP-based cassette exchange in somatic cells followed by nuclear transfer.
      Transposase-catalyzed transgenesis in a large mammalian species expands the
      arsenal of transgenic technologies for use in domestic animals and will
      facilitate the development of large animal models for human diseases.

PMID- 21897846
TI  - Lethal and pre-lethal effects of a fungal biopesticide contribute to substantial
      and rapid control of malaria vectors.
AB  - Rapidly emerging insecticide resistance is creating an urgent need for new active
      ingredients to control the adult mosquitoes that vector malaria. Biopesticides
      based on the spores of entomopathogenic fungi have shown considerable promise by
      causing very substantial mortality within 7-14 days of exposure. This mortality
      will generate excellent malaria control if there is a high likelihood that
      mosquitoes contact fungi early in their adult lives. However, where contact rates
      are lower, as might result from poor pesticide coverage, some mosquitoes will
      contact fungi one or more feeding cycles after they acquire malaria, and so risk
      transmitting malaria before the fungus kills them. Critics have argued that 'slow
      acting' fungal biopesticides are, therefore, incapable of delivering malaria
      control in real-world contexts. Here, utilizing standard WHO laboratory
      protocols, we demonstrate effective action of a biopesticide much faster than
      previously reported. Specifically, we show that transient exposure to clay tiles
      sprayed with a candidate biopesticide comprising spores of a natural isolate of
      Beauveria bassiana, could reduce malaria transmission potential to zero within a
      feeding cycle. The effect resulted from a combination of high mortality and rapid
      fungal-induced reduction in feeding and flight capacity. Additionally, multiple
      insecticide-resistant lines from three key African malaria vector species were
      completely susceptible to fungus. Thus, fungal biopesticides can block
      transmission on a par with chemical insecticides, and can achieve this where
      chemical insecticides have little impact. These results support broadening the
      current vector control paradigm beyond fast-acting chemical toxins.

PMID- 21897847
TI  - Genetic differentiation of the Western Capercaillie highlights the importance of
      South-eastern Europe for understanding the species phylogeography.
AB  - The Western Capercaillie (Tetrao urogallus L.) is a grouse species of open boreal
      or high altitude forests of Eurasia. It is endangered throughout most mountain
      range habitat areas in Europe. Two major genetically identifiable lineages of
      Western Capercaillie have been described to date: the southern lineage at the
      species' southernmost range of distribution in Europe, and the boreal lineage. We
      address the question of genetic differentiation of capercaillie populations from
      the Rhodope and Rila Mountains in Bulgaria, across the Dinaric Mountains to the
      Slovenian Alps. The two lineages' contact zone and resulting conservation
      strategies in this so-far understudied area of distribution have not been
      previously determined. The results of analysis of mitochondrial DNA control
      region sequences of 319 samples from the studied populations show that Alpine
      populations were composed exclusively of boreal lineage; Dinaric populations of
      both, but predominantly (96%) of boreal lineage; and Rhodope-Rila populations
      predominantly (>90%) of southern lineage individuals. The Bulgarian mountains
      were identified as the core area of the southern lineage, and the Dinaric
      Mountains as the western contact zone between both lineages in the Balkans.
      Bulgarian populations appeared genetically distinct from Alpine and Dinaric
      populations and exhibited characteristics of a long-term stationary population,
      suggesting that they should be considered as a glacial relict and probably a
      distinct subspecies. Although all of the studied populations suffered a decline
      in the past, the significantly lower level of genetic diversity when compared
      with the neighbouring Alpine and Bulgarian populations suggests that the isolated
      Dinaric capercaillie is particularly vulnerable to continuing population decline.
      The results are discussed in the context of conservation of the species in the
      Balkans, its principal threats and legal protection status. Potential
      conservation strategies should consider the existence of the two lineages and
      their vulnerable Dinaric contact zone and support the specificities of the
      populations.

PMID- 21897849
TI  - Umatilla virus genome sequencing and phylogenetic analysis: identification of
      stretch lagoon orbivirus as a new member of the Umatilla virus species.
AB  - The genus Orbivirus, family Reoviridae, includes 22 species of viruses with
      genomes composed of ten segments of linear dsRNA that are transmitted between
      their vertebrate hosts by insects or ticks, or with no identified vectors. Full
      genome sequence data are available for representative isolates of the insect
      borne mammalian orbiviruses (including bluetongue virus), as well as a tick borne
      avian orbivirus (Great Island virus). However, no sequence data are as yet
      available for the mosquito borne avian orbiviruses.We report full-length, whole
      genome sequence data for Umatilla virus (UMAV), a mosquito borne avian orbivirus
      from the USA, which belongs to the species Umatilla virus. Comparisons of
      conserved genome segments 1, 2 and 8 (Seg-1, Seg-2 and Seg-8) - encoding the
      polymerase-VP1, sub-core 'T2' protein and core-surface 'T13' protein,
      respectively, show that UMAV groups with the mosquito transmitted mammalian
      orbiviruses. The highest levels of sequence identity were detected between UMAV
      and Stretch Lagoon orbivirus (SLOV) from Australia, showing that they belong to
      the same virus species (with nt/aa identity of 76.04%/88.07% and 77.96%/95.36% in
      the polymerase and T2 genes and protein, respectively). The data presented here
      has assisted in identifying the SLOV as a member of the Umatilla serogroup. This
      sequence data reported here will also facilitate identification of new isolates,
      and epidemiological studies of viruses belonging to the species Umatilla virus.

PMID- 21897848
TI  - Profiling trait anxiety: transcriptome analysis reveals cathepsin B (Ctsb) as a
      novel candidate gene for emotionality in mice.
AB  - Behavioral endophenotypes are determined by a multitude of counteracting but
      precisely balanced molecular and physiological mechanisms. In this study, we aim
      to identify potential novel molecular targets that contribute to the multigenic
      trait "anxiety". We used microarrays to investigate the gene expression profiles
      of different brain regions within the limbic system of mice which were
      selectively bred for either high (HAB) or low (LAB) anxiety-related behavior, and
      also show signs of comorbid depression-like behavior. We identified and confirmed
      sex-independent differences in the basal expression of 13 candidate genes, using
      tissue from the entire brain, including coronin 7 (Coro7), cathepsin B (Ctsb),
      muscleblind-like 1 (Mbnl1), metallothionein 1 (Mt1), solute carrier family 25
      member 17 (Slc25a17), tribbles homolog 2 (Trib2), zinc finger protein 672
      (Zfp672), syntaxin 3 (Stx3), ATP-binding cassette, sub-family A member 2 (Abca2),
      ectonucleotide pyrophosphatase/phosphodiesterase 5 (Enpp5), high mobility group
      nucleosomal binding domain 3 (Hmgn3) and pyruvate dehydrogenase beta (Pdhb).
      Additionally, we confirmed brain region-specific differences in the expression of
      synaptotagmin 4 (Syt4).Our identification of about 90 polymorphisms in Ctsb
      suggested that this gene might play a critical role in shaping our mouse model's
      behavioral endophenotypes. Indeed, the assessment of anxiety-related and
      depression-like behaviors of Ctsb knock-out mice revealed an increase in
      depression-like behavior in females. Altogether, our results suggest that Ctsb
      has significant effects on emotionality, irrespective of the tested mouse strain,
      making it a promising target for future pharmacotherapy.

PMID- 21897850
TI  - BAFF promotes Th17 cells and aggravates experimental autoimmune
      encephalomyelitis.
AB  - BACKGROUND: BAFF, in addition to promoting B cell survival and differentiation,
      may affect T cells. The objective of this study was to determine the effect of
      BAFF on Th17 cell generation and its ramifications for the Th17 cell-driven
      disease, EAE. METHODOLOGY/PRINCIPAL FINDINGS: Th17 cells were increased in BAFF
      Tg B6 (B6.BTg) mice and decreased in B6.Baff(-/-) mice. Th17 cells in B6.Baff(-/
      ) mice bearing a BAFF Tg (B6.Baff(-/-).BTg mice) were identical to those in
      B6.BTg mice, indicating that membrane BAFF is dispensable for Th17 cell
      generation as long as soluble BAFF is plentiful. In T + non-T cell criss-cross co
      cultures, Th17 cell generation was greatest in cultures containing B6.BTg T cells
      and lowest in cultures containing B6.Baff(-/-) T cells, regardless of the source
      of non-T cells. In cultures containing only T cells, Th17 cell generation
      followed an identical pattern. CD4(+) cell expression of CD126 (IL-6R alpha
      chain) was increased in B6.BTg mice and decreased in B6.Baff(-/-) mice, and
      activation of STAT3 following stimulation with IL-6 + TGF-beta was also greatest
      in B6.BTg cells and lowest in B6.Baff(-/-) cells. EAE was clinically and
      pathologically most severe in B6.BTg mice and least severe in B6.Baff(-/-) mice
      and correlated with MOG(35-55) peptide-induced Th17 cell responses.
      CONCLUSIONS/SIGNIFICANCE: Collectively, these findings document a contribution of
      BAFF to pathogenic Th17 cell responses and suggest that BAFF antagonism may be
      efficacious in Th17 cell-driven diseases.

PMID- 21897851
TI  - Quantification of age-dependent somatic CAG repeat instability in Hdh CAG knock
      in mice reveals different expansion dynamics in striatum and liver.
AB  - BACKGROUND: Age at onset of Huntington's disease (HD) is largely determined by
      the CAG trinucleotide repeat length in the HTT gene. Importantly, the CAG repeat
      undergoes tissue-specific somatic instability, prevalent in brain regions that
      are disease targets, suggesting a potential role for somatic CAG repeat
      instability in modifying HD pathogenesis. Thus, understanding underlying
      mechanisms of somatic CAG repeat instability may lead to discoveries of novel
      therapeutics for HD. Investigation of the dynamics of the CAG repeat size changes
      over time may provide insights into the mechanisms underlying CAG repeat
      instability. METHODOLOGY/PRINCIPAL FINDINGS: To understand how the HTT CAG repeat
      length changes over time, we quantified somatic instability of the CAG repeat in
      Huntington's disease CAG knock-in mice from 2-16 months of age in liver,
      striatum, spleen and tail. The HTT CAG repeat in spleen and tail was very stable,
      but that in liver and striatum expanded over time at an average rate of one CAG
      per month. Interestingly, the patterns of repeat instability were different
      between liver and striatum. Unstable CAG repeats in liver repeatedly gained
      similar sizes of additional CAG repeats (approximately two CAGs per month),
      maintaining a distinct population of unstable repeats. In contrast, unstable CAG
      repeats in striatum gained additional repeats with different sizes resulting in
      broadly distributed unstable CAG repeats. Expanded CAG repeats in the liver were
      highly enriched in polyploid hepatocytes, suggesting that the pattern of liver
      instability may reflect the restriction of the unstable repeats to a unique cell
      type. CONCLUSIONS/SIGNIFICANCE: Our results are consistent with repeat expansion
      occurring as a consequence of recurrent small repeat insertions that differ in
      different tissues. Investigation of the specific mechanisms that underlie liver
      and striatal instability will contribute to our understanding of the relationship
      between instability and disease and the means to intervene in this process.

PMID- 21897853
TI  - Detection, properties, and frequency of local calcium release from the
      sarcoplasmic reticulum in teleost cardiomyocytes.
AB  - Calcium release from the sarcoplasmic reticulum (SR) plays a central role in the
      regulation of cardiac contraction and rhythm in mammals and humans but its role
      is controversial in teleosts. Since the zebrafish is an emerging model for
      studies of cardiovascular function and regeneration we here sought to determine
      if basic features of SR calcium release are phylogenetically conserved. Confocal
      calcium imaging was used to detect spontaneous calcium release (calcium sparks
      and waves) from the SR. Calcium sparks were detected in 16 of 38 trout atrial
      myocytes and 6 of 15 ventricular cells. The spark amplitude was 1.45+/-0.03 times
      the baseline fluorescence and the time to half maximal decay of sparks was 27+/-3
      ms. Spark frequency was 0.88 sparks um(-1) min(-1) while calcium waves were 8.5
      times less frequent. Inhibition of SR calcium uptake reduced the calcium
      transient (F/F(0)) from 1.77+/-0.17 to 1.12+/-0.18 (p = 0.002) and abolished
      calcium sparks and waves. Moreover, elevation of extracellular calcium from 2 to
      10 mM promoted early and delayed afterdepolarizations (from 0.6+/-0.3 min(-1) to
      8.1+/-2.0 min(-1), p = 0.001), demonstrating the ability of SR calcium release to
      induce afterdepolarizations in the trout heart. Calcium sparks of similar width
      and duration were also observed in zebrafish ventricular myocytes. In conclusion,
      this is the first study to consistently report calcium sparks in teleosts and
      demonstrate that the basic features of calcium release through the ryanodine
      receptor are conserved, suggesting that teleost cardiac myocytes is a relevant
      model to study the functional impact of abnormal SR function.

PMID- 21897852
TI  - Bone mineral density in HIV-negative men participating in a tenofovir pre
      exposure prophylaxis randomized clinical trial in San Francisco.
AB  - BACKGROUND: Pre-exposure prophylaxis (PrEP) trials are evaluating regimens
      containing tenofovir-disoproxil fumarate (TDF) for HIV prevention. We determined
      the baseline prevalence of low bone mineral density (BMD) and the effect of TDF
      on BMD in men who have sex with men (MSM) in a PrEP trial in San Francisco.
      METHODS/FINDINGS: We evaluated 1) the prevalence of low BMD using Dual Energy X
      ray Absorptiometry (DEXA) in a baseline cohort of 210 HIV-uninfected MSM who
      screened for a randomized clinical trial of daily TDF vs. placebo, and 2) the
      effects of TDF on BMD in a longitudinal cohort of 184 enrolled men. Half began
      study drug after a 9-month delay to evaluate changes in risk behavior associated
      with pill-use. At baseline, 20 participants (10%) had low BMD (Z score<=-2.0 at
      the L2-L4 spine, total hip, or femoral neck). Low BMD was associated with
      amphetamine (OR = 5.86, 95% CI 1.70-20.20) and inhalant (OR = 4.57, 95% CI 1.32
      15.81) use; men taking multivitamins, calcium, or vitamin D were less likely to
      have low BMD at baseline (OR = 0.26, 95% CI 0.10-0.71). In the longitudinal
      analysis, there was a 1.1% net decrease in mean BMD in the TDF vs. the pre
      treatment/placebo group at the femoral neck (95% CI 0.4-1.9%), 0.8% net decline
      at the total hip (95% CI 0.3-1.3%), and 0.7% at the L2-L4 spine (95% CI -0.1
      1.5%). At 24 months, 13% vs. 6% of participants experienced >5% BMD loss at the
      femoral neck in the TDF vs. placebo groups (p = 0.13). CONCLUSIONS: Ten percent
      of HIV-negative MSM had low BMD at baseline. TDF use resulted in a small but
      statistically significant decline in BMD at the total hip and femoral neck.
      Larger studies with longer follow-up are needed to determine the trajectory of
      BMD changes and any association with clinical fractures. TRIAL REGISTRATION:
      ClinicalTrials.gov: NCT00131677.

PMID- 21897854
TI  - A poorly known high-latitude parasitoid wasp community: unexpected diversity and
      dramatic changes through time.
AB  - Climate change will have profound and unanticipated effects on species
      distributions. The pace and nature of this change is largely unstudied,
      especially for the most diverse elements of terrestrial communities--the
      arthropods--here we have only limited knowledge concerning the taxonomy and the
      ecology of these groups. Because Arctic ecosystems have already experienced
      significant increases in temperature over the past half century, shifts in
      community structure may already be in progress. Here we utilise collections of a
      particularly hyperdiverse insect group--parasitoid wasps (Hymenoptera;
      Braconidae; Microgastrinae)--at Churchill, Manitoba, Canada in the early and mid
      twentieth century to compare the composition of the contemporary community to
      that present 50-70 years ago. Morphological and DNA barcoding results revealed
      the presence of 79 species of microgastrine wasps in collections from Churchill,
      but we estimate that 20% of the local fauna awaits detection. Species composition
      and diversity between the two time periods differ significantly; species that
      were most common in historic collections were not found in contemporary
      collections and vice versa. Using barcodes we compared these collections to
      others from across North America; contemporary Churchill species are most
      affiliated with more south-western collections, while historic collections were
      more affiliated with eastern collections. The past five decades has clearly seen
      a dramatic change of species composition within the area studied coincident with
      rising temperature.

PMID- 21897856
TI  - Global distribution of Polaromonas phylotypes--evidence for a highly successful
      dispersal capacity.
AB  - Bacteria from the genus Polaromonas are dominant phylotypes in clone libraries
      and culture collections from polar and high-elevation environments. Although
      Polaromonas has been found on six continents, we do not know if the same
      phylotypes exist in all locations or if they exhibit genetic isolation by
      distance patterns. To examine their biogeographic distribution, we analyzed all
      available, long-read 16S rRNA gene sequences of Polaromonas phylotypes from
      glacial and periglacial environments across the globe. Using genetic isolation by
      geographic distance analyses, including Mantel tests and Mantel correlograms, we
      found that Polaromonas phylotypes are globally distributed showing weak isolation
      by distance patterns at global scales. More focused analyses using discrete,
      equally sampled distances classes, revealed that only two distance classes (out
      of 12 total) showed significant spatial structuring. Overall, our analyses show
      that most Polaromonas phylotypes are truly globally distributed, but that some,
      as yet unknown, environmental variable may be selecting for unique phylotypes at
      a minority of our global sites. Analyses of aerobiological and genomic data
      suggest that Polaromonas phylotypes are globally distributed as dormant cells
      through high-elevation air currents; Polaromonas phylotypes are common in air and
      snow samples from high altitudes, and a glacial-ice metagenome and the two
      sequenced Polaromonas genomes contain the gene hipA, suggesting that Polaromonas
      can form dormant cells.

PMID- 21897855
TI  - High fat diet induces formation of spontaneous liposarcoma in mouse adipose
      tissue with overexpression of interleukin 22.
AB  - Interleukin 22 (IL-22) is a T-cell secreted cytokine that modulates inflammatory
      response in nonhematopoietic tissues such as epithelium and liver. The function
      of IL-22 in adipose tissue is currently unknown. We generated a transgenic mouse
      model with overexpression of IL-22 specifically in adipose tissue. The IL-22
      transgenic mice had no apparent changes in obesity and insulin resistance after
      feeding with high fat diet (HFD). Unexpectedly, all the IL-22 transgenic mice fed
      with HFD for four months developed spontaneous tumors in epididymal adipose
      tissue. Histological analysis indicated that the tumors were well-differentiated
      liposarcomas with infiltration of inflammatory cells. IL-22 overexpression
      promotes production of inflammatory cytokines such as IL-1beta and IL-10 and
      stimulates ERK phosphorylation in adipose tissue. Furthermore, IL-22 treatment in
      differentiated 3T3-L1 adipocytes could induce IL-1beta and IL-10 expression,
      together with stimulation of ERK phosphorylation. Taken together, our study not
      only established a novel mouse model with spontaneous liposarcoma, but also
      revealed that IL-22 overexpression may collaborate with diet-induced obesity to
      impact on tumor development in mouse.

PMID- 21897857
TI  - Acute toxicity of the antifouling compound butenolide in non-target organisms.
AB  - Butenolide [5-octylfuran-2(5H)-one] is a recently discovered and very promising
      anti-marine-fouling compound. In this study, the acute toxicity of butenolide was
      assessed in several non-target organisms, including micro algae, crustaceans, and
      fish. Results were compared with previously reported results on the effective
      concentrations used on fouling (target) organisms. According to OECD's guideline,
      the predicted no effect concentration (PNEC) was 0.168 ug l(-1), which was among
      one of the highest in representative new biocides. Mechanistically, the phenotype
      of butenolide-treated Danio rerio (zebrafish) embryos was similar to the
      phenotype of the pro-caspase-3 over-expression mutant with pericardial edema,
      small eyes, small brains, and increased numbers of apoptotic cells in the bodies
      of zebrafish embryos. Butenolide also induced apoptosis in HeLa cells, with the
      activation of c-Jun N-terminal kinases (JNK), Bcl-2 family proteins, and caspases
      and proteasomes/lysosomes involved in this process. This is the first detailed
      toxicity and toxicology study on this antifouling compound.

PMID- 21897858
TI  - Combinations of SNPs related to signal transduction in bipolar disorder.
AB  - Any given single nucleotide polymorphism (SNP) in a genome may have little or no
      functional impact. A biologically significant effect may possibly emerge only
      when a number of key SNP-related genotypes occur together in a single organism.
      Thus, in analysis of many SNPs in association studies of complex diseases, it may
      be useful to look at combinations of genotypes. Genes related to signal
      transmission, e.g., ion channel genes, may be of interest in this respect in the
      context of bipolar disorder. In the present study, we analysed 803 SNPs in 55
      genes related to aspects of signal transmission and calculated all combinations
      of three genotypes from the 3*803 SNP genotypes for 1355 controls and 607
      patients with bipolar disorder. Four clusters of patient-specific combinations
      were identified. Permutation tests indicated that some of these combinations
      might be related to bipolar disorder. The WTCCC bipolar dataset were use for
      replication, 469 of the 803 SNP were present in the WTCCC dataset either directly
      (n = 132) or by imputation (n = 337) covering 51 of our selected genes. We found
      three clusters of patient-specific 3*SNP combinations in the WTCCC dataset.
      Different SNPs were involved in the clusters in the two datasets. The present
      analyses of the combinations of SNP genotypes support a role for both genetic
      heterogeneity and interactions in the genetic architecture of bipolar disorder.

PMID- 21897859
TI  - Asthmatics exhibit altered oxylipin profiles compared to healthy individuals
      after subway air exposure.
AB  - BACKGROUND: Asthma is a chronic inflammatory lung disease that causes significant
      morbidity and mortality worldwide. Air pollutants such as particulate matter (PM)
      and oxidants are important factors in causing exacerbations in asthmatics, and
      the source and composition of pollutants greatly affects pathological
      implications. OBJECTIVES: This randomized crossover study investigated responses
      of the respiratory system to Stockholm subway air in asthmatics and healthy
      individuals. Eicosanoids and other oxylipins were quantified in the distal lung
      to provide a measure of shifts in lipid mediators in association with exposure to
      subway air relative to ambient air. METHODS: Sixty-four oxylipins representing
      the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 (CYP) metabolic
      pathways were screened using liquid chromatography-tandem mass spectrometry (LC
      MS/MS) of bronchoalveolar lavage (BAL)-fluid. Validations through
      immunocytochemistry staining of BAL-cells were performed for 15-LOX-1, COX-1, COX
      2 and peroxisome proliferator-activated receptor gamma (PPARgamma). Multivariate
      statistics were employed to interrogate acquired oxylipin and immunocytochemistry
      data in combination with patient clinical information. RESULTS: Asthmatics and
      healthy individuals exhibited divergent oxylipin profiles following exposure to
      ambient and subway air. Significant changes were observed in 8 metabolites of
      linoleic- and alpha-linolenic acid synthesized via the 15-LOX pathway, and of the
      COX product prostaglandin E(2) (PGE(2)). Oxylipin levels were increased in
      healthy individuals following exposure to subway air, whereas asthmatics
      evidenced decreases or no change. CONCLUSIONS: Several of the altered oxylipins
      have known or suspected bronchoprotective or anti-inflammatory effects,
      suggesting a possible reduced anti-inflammatory response in asthmatics following
      exposure to subway air. These observations may have ramifications for sensitive
      subpopulations in urban areas.

PMID- 21897860
TI  - Dynamic regulation of Oct1 during mitosis by phosphorylation and ubiquitination.
AB  - BACKGROUND: Transcription factor Oct1 regulates multiple cellular processes. It
      is known to be phosphorylated during the cell cycle and by stress, however the
      upstream kinases and downstream consequences are not well understood. One of
      these modified forms, phosphorylated at S335, lacks the ability to bind DNA.
      Other modification states besides phosphorylation have not been described.
      METHODOLOGY/PRINCIPAL FINDINGS: We show that Oct1 is phosphorylated at S335 in
      the Oct1 DNA binding domain during M-phase by the NIMA-related kinase Nek6.
      Phospho-Oct1 is also ubiquitinated. Phosphorylation excludes Oct1 from mitotic
      chromatin. Instead, Oct1(pS335) concentrates at centrosomes, mitotic spindle
      poles, kinetochores and the midbody. Oct1 siRNA knockdown diminishes the signal
      at these locations. Both Oct1 ablation and overexpression result in abnormal
      mitoses. S335 is important for the overexpression phenotype, implicating this
      residue in mitotic regulation. Oct1 depletion causes defects in spindle
      morphogenesis in Xenopus egg extracts, establishing a mitosis-specific function
      of Oct1. Oct1 colocalizes with lamin B1 at the spindle poles and midbody. At the
      midbody, both proteins are mutually required to correctly localize the other. We
      show that phospho-Oct1 is modified late in mitosis by non-canonical K11-linked
      polyubiquitin chains. Ubiquitination requires the anaphase-promoting complex, and
      we further show that the anaphase-promoting complex large subunit APC1 and
      Oct1(pS335) interact. CONCLUSIONS/SIGNIFICANCE: These findings reveal mechanistic
      coupling between Oct1 phosphorylation and ubquitination during mitotic
      progression, and a role for Oct1 in mitosis.

PMID- 21897861
TI  - Betacellulin-induced beta cell proliferation and regeneration is mediated by
      activation of ErbB-1 and ErbB-2 receptors.
AB  - BACKGROUND: Betacellulin (BTC), a member of the epidermal growth factor family,
      is known to play an important role in regulating growth and differentiation of
      pancreatic beta cells. Growth-promoting actions of BTC are mediated by epidermal
      growth factor receptors (ErbBs), namely ErbB-1, ErbB-2, ErbB-3 and ErbB-4;
      however, the exact mechanism for beta cell proliferation has not been elucidated.
      Therefore, we investigated which ErbBs are involved and some molecular mechanisms
      by which BTC regulates beta cell proliferation. METHODOLOGY/PRINCIPAL FINDINGS:
      The expression of ErbB-1, ErbB-2, ErbB-3, and ErbB-4 mRNA was detected by RT-PCR
      in both a beta cell line (MIN-6 cells) and C57BL/6 mouse islets.
      Immunoprecipitation and western blotting analysis showed that BTC treatment of
      MIN-6 cells induced phosphorylation of only ErbB-1 and ErbB-2 among the four EGF
      receptors. BTC treatment resulted in DNA synthetic activity, cell cycle
      progression, and bromodeoxyuridine (BrdU)-positive staining. The proliferative
      effect was blocked by treatment with AG1478 or AG825, specific tyrosine kinase
      inhibitors of ErbB-1 and ErbB-2, respectively. BTC treatment increased mRNA and
      protein levels of insulin receptor substrate-2 (IRS-2), and this was blocked by
      the ErbB-1 and ErbB-2 inhibitors. Inhibition of IRS-2 by siRNA blocked cell cycle
      progression induced by BTC treatment. Streptozotocin-induced diabetic mice
      injected with a recombinant adenovirus expressing BTC and treated with AG1478 or
      AG825 showed reduced islet size, reduced numbers of BrdU-positive cells in the
      islets, and did not attain BTC-mediated remission of diabetes.
      CONCLUSIONS/SIGNIFICANCE: These results suggest that BTC exerts proliferative
      activity on beta cells through the activation of ErbB-1 and ErbB-2 receptors,
      which may increase IRS-2 expression, contributing to the regeneration of beta
      cells.

PMID- 21897862
TI  - A toxin-antitoxin module in Bacillus subtilis can both mitigate and amplify
      effects of lethal stress.
AB  - BACKGROUND: Bacterial type-2 (protein-protein) toxin-antitoxin (TA) modules are
      two-gene operons that are thought to participate in the response to stress.
      Previous work with Escherichia coli has led to a debate in which some
      investigators conclude that the modules protect from stress, while others argue
      that they amplify lethal stress and lead to programmed cell death. To avoid
      ambiguity arising from the presence of multiple TA modules in E. coli, the effect
      of the sole type-2 toxin-antitoxin module of Bacillus subtilis was examined for
      several types of lethal stress. METHODOLOGY/PRINCIPAL FINDINGS: Genetic knockout
      of the toxin gene, ndoA (ydcE), conferred protection to lethal stressors that
      included kanamycin, moxifloxacin, hydrogen peroxide, and UV irradiation. However,
      at low doses of UV irradiation the ndoA deficiency increased lethality. Indeed,
      gradually increasing UV dose with the ndoA mutant revealed a crossover response-
      from the mutant being more sensitive than wild-type cells to being less
      sensitive. For high temperature and nutrient starvation, the toxin deficiency
      rendered cells hypersensitive. The ndoA deficiency also reduced sporulation
      frequency, indicating a role for toxin-antitoxin modules in this developmental
      process. In the case of lethal antimicrobial treatment, deletion of the toxin
      eliminated a surge in hydrogen peroxide accumulation observed in wild-type cells.
      CONCLUSIONS: A single toxin-antitoxin module can mediate two opposing effects of
      stress, one that lowers lethality and another that raises it. Protective effects
      are thought to arise from toxin-mediated inhibition of translation based on
      published work. The enhanced, stress-mediated killing probably involves toxin
      dependent accumulation of reactive oxygen species, since a deficiency in the NdoA
      toxin suppressed peroxide accumulation following antimicrobial treatment. The
      type and perhaps the level of stress appear to be important for determining
      whether this toxin will have a protective or detrimental effect.

PMID- 21897863
TI  - Understanding original antigenic sin in influenza with a dynamical system.
AB  - Original antigenic sin is the phenomenon in which prior exposure to an antigen
      leads to a subsequent suboptimal immune response to a related antigen. Immune
      memory normally allows for an improved and rapid response to antigens previously
      seen and is the mechanism by which vaccination works. I here develop a dynamical
      system model of the mechanism of original antigenic sin in influenza, clarifying
      and explaining the detailed spin-glass treatment of original antigenic sin. The
      dynamical system describes the viral load, the quantities of healthy and infected
      epithelial cells, the concentrations of naive and memory antibodies, and the
      affinities of naive and memory antibodies. I give explicit correspondences
      between the microscopic variables of the spin-glass model and those of the
      present dynamical system model. The dynamical system model reproduces the
      phenomenon of original antigenic sin and describes how a competition between
      different types of B cells compromises the overall effect of immune response. I
      illustrate the competition between the naive and the memory antibodies as a
      function of the antigenic distance between the initial and subsequent antigens.
      The suboptimal immune response caused by original antigenic sin is observed when
      the host is exposed to an antigen which has intermediate antigenic distance to a
      second antigen previously recognized by the host's immune system.

PMID- 21897864
TI  - Self-reported ethnicity and genetic ancestry in relation to oral cancer and pre
      cancer in Puerto Rico.
AB  - BACKGROUND: Hispanics are known to be an extremely diverse and genetically
      admixed ethnic group. The lack of methodologies to control for ethnicity and the
      unknown admixture in complex study populations of Hispanics has left a gap in
      understanding certain cancer disparity issues. Incidence rates for oral and
      pharyngeal cancer (OPC) in Puerto Rico are among the highest in the Western
      Hemisphere. We conducted an epidemiological study to examine risk and protective
      factors, in addition to possible genetic susceptibility components, for oral
      cancer and precancer in Puerto Rico. METHODOLOGY/PRINCIPAL FINDINGS: We recruited
      310 Puerto Rico residents who had been diagnosed with either an incident oral
      squamous cell carcinoma, oral precancer, or benign oral condition. Participants
      completed an in-person interview and contributed buccal cells for DNA extraction.
      ABI Biosystem TaqmanTM primer sets were used for genotyping 12 ancestry
      informative markers (AIMs). Ancestral group estimates were generated using
      maximum likelihood estimation software (LEADMIX), and additional principal
      component analysis was carried out to detect population substructures. We used
      unconditional logistic regression to assess the contribution of ancestry to the
      risk of being diagnosed with either an oral cancer or precancer while controlling
      for other potential confounders. The maximum likelihood estimates showed that
      study participants had a group average ancestry contribution of 69.9% European,
      24.5% African, and 5.7% detectable Native American. The African and Indigenous
      American group estimates were significantly higher than anticipated. Neither self
      identified ethnicity nor ancestry markers showed any significant associations
      with oral cancer/precancer risk in our study. CONCLUSIONS/SIGNIFICANCE: The
      application of ancestry informative markers (AIMs), specifically designed for
      Hispanics, suggests no hidden population substructure is present based on our
      sampling and provides a viable approach for the evaluation and control of
      ancestry in future studies involving Hispanic populations.

PMID- 21897865
TI  - Inter-observer agreement on subjects' race and race-informative characteristics.
AB  - Health and socioeconomic disparities tend to be experienced along racial and
      ethnic lines, but investigators are not sure how individuals are assigned to
      groups, or how consistent this process is. To address these issues, 1,919
      orthodontic patient records were examined by at least two observers who estimated
      each individual's race and the characteristics that influenced each estimate.
      Agreement regarding race is high for African and European Americans, but not as
      high for Asian, Hispanic, and Native Americans. The indicator observers most
      often agreed upon as important in estimating group membership is name, especially
      for Asian and Hispanic Americans. The observers, who were almost all European
      American, most often agreed that skin color is an important indicator of race
      only when they also agreed the subject was European American. This suggests that
      in a diverse community, light skin color is associated with a particular group,
      while a range of darker shades can be associated with members of any other group.
      This research supports comparable studies showing that race estimations in
      medical records are likely reliable for African and European Americans, but are
      less so for other groups. Further, these results show that skin color is not
      consistently the primary indicator of an individual's race, but that other
      characteristics such as facial features add significant information.

PMID- 21897867
TI  - Quantifying the ocean, freshwater and human effects on year-to-year variability
      of one-sea-winter Atlantic salmon angled in multiple Norwegian rivers.
AB  - Many Atlantic salmon, Salmo salar, populations are decreasing throughout the
      species' distributional range probably due to several factors acting in concert.
      A number of studies have documented the influence of freshwater and ocean
      conditions, climate variability and human impacts resulting from impoundment and
      aquaculture. However, most previous research has focused on analyzing single or
      only a few populations, and quantified isolated effects rather than handling
      multiple factors in conjunction. By using a multi-river mixed-effects model we
      estimated the effects of oceanic and river conditions, as well as human impacts,
      on year-to-year and between-river variability across 60 time series of
      recreational catch of one-sea-winter salmon (grilse) from Norwegian rivers over
      29 years (1979-2007). Warm coastal temperatures at the time of smolt entrance
      into the sea and increased water discharge during upstream migration of mature
      fish were associated with higher rod catches of grilse. When hydropower stations
      were present in the course of the river systems the strength of the relationship
      with runoff was reduced. Catches of grilse in the river increased significantly
      following the reduction of the harvesting of this life-stage at sea. However, an
      average decreasing temporal trend was still detected and appeared to be stronger
      in the presence of salmon farms on the migration route of smolts in coastal/fjord
      areas. These results suggest that both ocean and freshwater conditions in
      conjunction with various human impacts contribute to shape interannual
      fluctuations and between-river variability of wild Atlantic salmon in Norwegian
      rivers. Current global change altering coastal temperature and water flow
      patterns might have implications for future grilse catches, moreover, positioning
      of aquaculture facilities as well as the implementation of hydropower schemes or
      other encroachments should be made with care when implementing management actions
      and searching for solutions to conserve this species.

PMID- 21897866
TI  - In silico approach to inhibition of signaling pathways of Toll-like receptors 2
      and 4 by ST2L.
AB  - Toll-like receptors (TLRs) activate a potent immunostimulatory response. There is
      clear evidence that overactivation of TLRs leads to infectious and inflammatory
      diseases. Recent biochemical studies have shown that the membrane-bound form of
      ST2 (ST2L), a member of the Toll-like/IL-1 receptor superfamily, negatively
      regulates MyD88-dependent TLR signaling pathways by sequestrating the adapters
      MyD88 and Mal (TIRAP). Specifically, ST2L attenuates the recruitment of Mal and
      MyD88 adapters to their receptors through its intracellular TIR domain. Thus,
      ST2L is a potent molecule that acts as a key regulator of endotoxin tolerance and
      modulates innate immunity. So far, the inhibitory mechanism of ST2L at the
      molecular level remains elusive. To develop a working hypothesis for the
      interactions between ST2L, TLRs (TLR1, 2, 4, and 6), and adapter molecules (MyD88
      and Mal), we constructed three-dimensional models of the TIR domains of TLR4, 6,
      Mal, and ST2L based on homology modeling. Since the crystal structures of the TIR
      domains of TLR1, 2 as well as the NMR solution structure of MyD88 are known, we
      utilized these structures in our analysis. The TIR domains of TLR1, 2, 4, 6,
      MyD88, Mal and ST2L were subjected to molecular dynamics (MD) simulations in an
      explicit solvent environment. The refined structures obtained from the MD
      simulations were subsequently used in molecular docking studies to probe for
      potential sites of interactions. Through protein-protein docking analysis, models
      of the essential complexes involved in TLR2 and 4 signaling and ST2L inhibiting
      processes were developed. Our results suggest that ST2L may exert its inhibitory
      effect by blocking the molecular interface of Mal and MyD88 adapters mainly
      through its BB-loop region. Our predicted oligomeric signaling models may provide
      a basis for the understanding of the assembly process of TIR domain interactions,
      which has thus far proven to be difficult via in vivo studies.

PMID- 21897868
TI  - Genotyping of Capreolus pygargus fossil DNA from Denisova cave reveals
      phylogenetic relationships between ancient and modern populations.
AB  - BACKGROUND: The extant roe deer (Capreolus Gray, 1821) includes two species: the
      European roe deer (C. capreolus) and the Siberian roe deer (C. pygargus) that are
      distinguished by morphological and karyotypical differences. The Siberian roe
      deer occupies a vast area of Asia and is considerably less studied than the
      European roe deer. Modern systematics of the Siberian roe deer remain
      controversial with 4 morphological subspecies. Roe deer fossilized bones are
      quite abundant in Denisova cave (Altai Mountains, South Siberia), where dozens of
      both extant and extinct mammalian species from modern Holocene to Middle
      Pleistocene have been retrieved. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed a
      629 bp fragment of the mitochondrial control region from ancient bones of 10
      Holocene and four Pleistocene Siberian roe deer from Denisova cave as well as 37
      modern specimen belonging to populations from Altai, Tian Shan (Kyrgyzstan),
      Yakutia, Novosibirsk region and the Russian Far East. Genealogical
      reconstructions indicated that most Holocene haplotypes were probably ancestral
      for modern roe deer populations of Western Siberia and Tian Shan. One of the
      Pleistocene haplotypes was possibly ancestral for modern Yakutian populations,
      and two extinct Pleistocene haplotypes were close to modern roe deer from Tian
      Shan and Yakutia. Most modern geographical populations (except for West Siberian
      Plains) are heterogeneous and there is some tentative evidence for structure.
      However, we did not find any distinct phylogenetic signal characterizing
      particular subspecies in either modern or ancient samples.
      CONCLUSION/SIGNIFICANCE: Analysis of mitochondrial DNA from both ancient and
      modern samples of Siberian roe deer shed new light on understanding the
      evolutionary history of roe deer. Our data indicate that during the last 50,000
      years multiple replacements of populations of the Siberian roe deer took place in
      the Altai Mountains correlating with climatic changes. The Siberian roe deer
      represent a complex and heterogeneous species with high migration rates and
      without evident subspecies structure. Low genetic diversity of the West Siberian
      Plain population indicates a recent bottleneck or founder effect.

PMID- 21897869
TI  - A genome-wide linkage scan for distinct subsets of schizophrenia characterized by
      age at onset and neurocognitive deficits.
AB  - BACKGROUND: As schizophrenia is genetically and phenotypically heterogeneous,
      targeting genetically informative phenotypes may help identify greater linkage
      signals. The aim of the study is to evaluate the genetic linkage evidence for
      schizophrenia in subsets of families with earlier age at onset or greater
      neurocognitive deficits. METHODS: Patients with schizophrenia (n  =  1,207) and
      their first-degree relatives (n  =  1,035) from 557 families with schizophrenia
      were recruited from six data collection field research centers throughout Taiwan.
      Subjects completed a face-to-face semi-structured interview, the Continuous
      Performance Test (CPT), the Wisconsin Card Sorting Test, and were genotyped with
      386 microsatellite markers across the genome. RESULTS: A maximum nonparametric
      logarithm of odds (LOD) score of 4.17 at 2q22.1 was found in 295 families ranked
      by increasing age at onset, which had significant increases in the maximum LOD
      score compared with those obtained in initial linkage analyses using all
      available families. Based on this subset, a further subsetting by false alarm
      rate on the undegraded and degraded CPT obtained further increase in the nested
      subset-based LOD on 2q22.1, with a score of 7.36 in 228 families and 7.71 in 243
      families, respectively. CONCLUSION: We found possible evidence of linkage on
      chromosome 2q22.1 in families of schizophrenia patients with more CPT false alarm
      rates nested within the families with younger age at onset. These results
      highlight the importance of incorporating genetically informative phenotypes in
      unraveling the complex genetics of schizophrenia.

PMID- 21897870
TI  - Bacterial inactivation of wound infection in a human skin model by liquid-phase
      discharge plasma.
AB  - BACKGROUND: We investigate disinfection of a reconstructed human skin model
      contaminated with biofilm-formative Staphylococcus aureus employing plasma
      discharge in liquid. PRINCIPAL FINDINGS: We observed statistically significant
      3.83-log10 (p<0.001) and 1.59-log10 (p<0.05) decreases in colony forming units of
      adherent S. aureus bacteria and 24 h S. aureus biofilm culture with plasma
      treatment. Plasma treatment was associated with minimal changes in histological
      morphology and tissue viability determined by means of MTT assay. Spectral
      analysis of the plasma discharge indicated the presence of highly reactive atomic
      oxygen radicals (777 nm and 844 nm) and OH bands in the UV region. The
      contribution of these and other plasma-generated agents and physical conditions
      to the reduction in bacterial load are discussed. CONCLUSIONS: These findings
      demonstrate the potential of liquid plasma treatment as a potential adjunct
      therapy for chronic wounds.

PMID- 21897871
TI  - Expression of APOBEC3G/3F and G-to-A hypermutation levels in HIV-1-infected
      children with different profiles of disease progression.
AB  - OBJECTIVE: Increasing evidence has accumulated showing the role of APOBEC3G (A3G)
      and 3F (A3F) in the control of HIV-1 replication and disease progression in
      humans. However, very few studies have been conducted in HIV-infected children.
      Here, we analyzed the levels of A3G and A3F expression and induced G-to-A
      hypermutation in a group of children with distinct profiles of disease
      progression. METHODOLOGY/PRINCIPAL FINDINGS: Perinatally HIV-infected children
      were classified as progressors or long-term non-progressors according to criteria
      based on HIV viral load and CD4 T-cell counts over time. A group of uninfected
      control children were also enrolled in the study. PBMC proviral DNA was assessed
      for G-to-A hypermutation, whereas A3G and A3F mRNA were isolated and quantified
      through TaqMan(r) real-time PCR. No correlation was observed between disease
      progression and A3G/A3F expression or hypermutation levels. Although all children
      analyzed showed higher expression levels of A3G compared to A3F (an average fold
      of 5 times), a surprisingly high A3F-related hypermutation rate was evidenced in
      the cohort, irrespective of the child's disease progression profile. CONCLUSION:
      Our results contribute to the current controversy as to whether HIV disease
      progression is related to A3G/A3F enzymatic activity. To our knowledge, this is
      the first study analyzing A3G/F expression in HIV-infected children, and it may
      pave the way to a better understanding of the host factors governing HIV disease
      in the pediatric setting.

PMID- 21897872
TI  - Sensitization prevalence, antibody cross-reactivity and immunogenic peptide
      profile of Api g 2, the non-specific lipid transfer protein 1 of celery.
AB  - BACKGROUND: Celery (Apium graveolens) represents a relevant allergen source that
      can elicit severe reactions in the adult population. To investigate the
      sensitization prevalence and cross-reactivity of Api g 2 from celery stalks in a
      Mediterranean population and in a mouse model. METHODOLOGY: 786 non-randomized
      subjects from Italy were screened for IgE reactivity to rApi g 2, rArt v 3
      (mugwort pollen LTP) and nPru p 3 (peach LTP) using an allergen microarray.
      Clinical data of 32 selected patients with reactivity to LTP under investigation
      were evaluated. Specific IgE titers and cross-inhibitions were performed in ELISA
      and allergen microarray. Balb/c mice were immunized with purified LTPs; IgG
      titers were determined in ELISA and mediator release was examined using RBL-2H3
      cells. Simulated endolysosomal digestion was performed using microsomes obtained
      from human DCs. RESULTS: IgE testing showed a sensitization prevalence of 25.6%
      to Api g 2, 18.6% to Art v 3, and 28.6% to Pru p 3 and frequent co-sensitization
      and correlating IgE-reactivity was observed. 10/32 patients suffering from LTP
      related allergy reported symptoms upon consumption of celery stalks which mainly
      presented as OAS. Considerable IgE cross-reactivity was observed between Api g 2,
      Art v 3, and Pru p 3 with varying inhibition degrees of individual patients'
      sera. Simulating LTP mono-sensitization in a mouse model showed development of
      more congruent antibody specificities between Api g 2 and Art v 3. Notably,
      biologically relevant murine IgE cross-reactivity was restricted to the latter
      and diverse from Pru p 3 epitopes. Endolysosomal processing of LTP showed
      generation of similar clusters, which presumably represent T-cell peptides.
      CONCLUSIONS: Api g 2 represents a relevant celery stalk allergen in the LTP
      sensitized population. The molecule displays common B cell epitopes and
      endolysosomal peptides that encompass T cell epitopes with pollen and plant-food
      derived LTP.

PMID- 21897873
TI  - Synergistic activation of cardiac genes by myocardin and Tbx5.
AB  - Myocardial differentiation is associated with the activation and expression of an
      array of cardiac specific genes. However, the transcriptional networks that
      control cardiac gene expression are not completely understood. Myocardin is a
      cardiac and smooth muscle-specific expressed transcriptional coactivator of Serum
      Response Factor (SRF) and is able to potently activate cardiac and smooth muscle
      gene expression during development. We hypothesize that myocardin discriminates
      between cardiac and smooth muscle specific genes by associating with distinct co
      factors. Here, we show that myocardin directly interacts with Tbx5, a member of
      the T-box family of transcription factors involved in the Holt-Oram syndrome.
      Tbx5 synergizes with myocardin to activate expression of the cardiac specific
      genes atrial natriuretic factor (ANF) and alpha myosin heavy chain (alpha-MHC),
      but not that of smooth muscle specific genes SM22 or smooth muscle myosin heavy
      chain (SM-MHC). We found that this synergistic activation of shared target genes
      is dependent on the binding sites for Tbx5, T-box factor-Binding Elements (TBEs).
      Myocardin and Tbx5 physically interact and their interaction domains were mapped
      to the basic domain and the coil domain of myocardin and Tbx5, respectively. Our
      analysis demonstrates that the Tbx5G80R mutation, which leads to the Holt-Oram
      syndrome in humans, failed to synergize with myocardin to activate cardiac gene
      expression. These data uncover a key role for Tbx5 and myocardin in establishing
      the transcriptional foundation for cardiac gene activation and suggest that the
      interaction of myocardin and Tbx5 maybe involved in cardiac development and
      diseases.

PMID- 21897874
TI  - Unstable transcripts in Arabidopsis allotetraploids are associated with
      nonadditive gene expression in response to abiotic and biotic stresses.
AB  - Genome-wide analysis has documented differential gene expression between closely
      related species in plants and animals and nonadditive gene expression in hybrids
      and allopolyploids compared to the parents. In Arabidopsis, 15-43% of genes are
      expressed differently between the related species, Arabidopsis thaliana and
      Arabidopsis arenosa, the majority of which are nonadditively expressed
      (differently from mid-parent value) in allotetraploids. Nonadditive gene
      expression can be caused by transcriptional regulation through chromatin
      modifications, but the role of posttranscriptional regulation in nonadditive gene
      expression is largely unknown. Here we reported genome-wide analysis of mRNA
      decay in resynthesized Arabidopsis allotetraploids. Among ~26,000 annotated
      genes, over 1% of gene transcripts showed rapid decay with an estimated half-life
      of less than 60 minutes, and they are called allotetraploid genes with unstable
      transcripts (AlloGUTs). Remarkably, 30% of alloGUTs matched the nonadditively
      expressed genes, and their expression levels were negatively correlated with the
      decay rate. Compared to all genes, these nonadditively expressed alloGUTs were
      overrepresented 2-6-fold in the Gene Ontology (GOSlim) classifications in
      response to abiotic and biotic stresses, signal transduction, and transcription.
      Interestingly, the AlloGUTs include transcription factor genes that are highly
      inducible under stress conditions and circadian clock regulators that regulate
      growth in A. thaliana. These data suggest a role of mRNA stability in
      homoeologous gene expression in Arabidopsis allopolyploids. The enrichment of
      nonadditively expressed genes in stress-related pathways were commonly observed
      in Arabidopsis and other allopolyploids such as wheat and cotton, which may
      suggest a role for stress-mediated growth vigor in hybrids and allopolyploids.

PMID- 21897875
TI  - Interferon-beta signaling contributes to Ras transformation.
AB  - Increasing evidence has pointed to activated type I interferon signaling in
      tumors. However, the molecular basis for such activation and its role in
      tumorigenesis remain unclear. In the current studies, we report that activation
      of type I interferon (IFN) signaling in tumor cells is primarily due to elevated
      secretion of the type I interferon, IFN-beta. Studies in oncogene-transformed
      cells suggest that oncogenes such as Ras and Src can activate IFN-beta signaling.
      Significantly, elevated IFN-beta signaling in Ras-transformed mammary epithelial
      MCF-10A cells was shown to contribute to Ras transformation as evidenced by
      morphological changes, anchorage-independent growth, and migratory properties.
      Our results demonstrate for the first time that the type I IFN, IFN-beta,
      contributes to Ras transformation and support the notion that oncogene-induced
      cytokines play important roles in oncogene transformation.

PMID- 21897876
TI  - The combination of BH3-mimetic ABT-737 with the alkylating agent temozolomide
      induces strong synergistic killing of melanoma cells independent of p53.
AB  - Metastatic melanoma has poor prognosis and is refractory to most conventional
      chemotherapies. The alkylating agent temozolomide (TMZ) is commonly used in
      treating melanoma but has a disappointing response rate. Agents that can act
      cooperatively with TMZ and improve its efficacy are thus highly sought after. The
      BH3 mimetic ABT-737, which can induce apoptosis by targeting pro-survival Bcl-2
      family members, has been found to enhance the efficacy of many conventional
      chemotherapeutic agents in multiple cancers. We found that combining TMZ and ABT
      737 induced strong synergistic apoptosis in multiple human melanoma cell lines.
      When the drugs were used in combination in a mouse xenograft model, they
      drastically reduced tumor growth at concentrations where each individual drug had
      no significant effect. We found that TMZ treatment elevated p53 levels, and that
      the pro-apoptotic protein Noxa was elevated in TMZ/ABT-737 treated cells.
      Experiments with shRNA demonstrated that the synergistic effect of TMZ and ABT
      737 was largely dependent on Noxa. Experiments with nutlin-3, a p53 inducer,
      demonstrated that p53 induction was sufficient for synergistic cell death with
      ABT-737 in a Noxa-dependent fashion. However, p53 was not necessary for TMZ/ABT
      737 synergy as demonstrated by a p53-null line, indicating that TMZ and ABT-737
      together induce Noxa in a p53-independent fashion. These results demonstrate that
      targeting anti-apoptotic Bcl-2 members is a promising method for treating
      metastatic melanoma, and that clinical trials with TMZ and Bcl-2 inhibitors are
      warranted.

PMID- 21897877
TI  - Relevance of stereotyped B-cell receptors in the context of the molecular,
      cytogenetic and clinical features of chronic lymphocytic leukemia.
AB  - Highly homologous B-cell receptors, characterized by non-random combinations of
      immunoglobulin heavy-chain variable (IGHV) genes and heavy-chain complementarity
      determining region-3 (HCDR3), are expressed in a recurrent fraction of patients
      affected by chronic lymphocytic leukemia (CLL). We investigated the IGHV status
      of 1131 productive IG rearrangements from a panel of 1126 CLL patients from a
      multicenter Italian study group, and correlated the presence and class of HCDR3
      stereotyped subsets with the major cytogenetic alterations evaluated by FISH,
      molecular prognostic factors, and the time to first treatment (TTFT) of patients
      with early stage disease (Binet A). Stereotyped HCDR3 sequences were found in 357
      cases (31.7%), 231 of which (64.7%) were unmutated. In addition to the previously
      described subsets, 31 new putative stereotypes subsets were identified.
      Significant associations between different stereotyped HCDR3 sequences and
      molecular prognostic factors, such as CD38 and ZAP-70 expression, IGHV mutational
      status and genomic abnormalities were found. In particular, deletion of 17p13 was
      significantly represented in stereotype subset #1. Notably, subset #1 was
      significantly correlated with a substantially reduced TTFT compared to other CLL
      groups showing unmutated IGHV, ZAP-70 or CD38 positivity and unfavorable
      cytogenetic lesions including del(17)(p13). Moreover, subset #2 was strongly
      associated with deletion of 13q14, subsets #8 and #10 with trisomy 12, whereas
      subset #4 was characterized by the prevalent absence of the common cytogenetic
      abnormalities. Our data from a large and representative panel of CLL patients
      indicate that particular stereotyped HCDR3 sequences are associated with specific
      cytogenetic lesions and a distinct clinical outcome.

PMID- 21897879
TI  - Trends in food and drug administration inspection: A warning for the industry!

PMID- 21897878
TI  - A New Family of Biuret Hydrolases Involved in S-Triazine Ring Metabolism.
AB  - Biuret is an intermediate in the bacterial metabolism of s-triazine ring
      compounds and is occasionally used as a ruminant feed supplement. We used
      bioinformatics to identify a biuret hydrolase, an enzyme that has previously
      resisted efforts to stabilize, purify and characterize. This newly discovered
      enzyme is a member of the cysteine hydrolase superfamily, a family of enzymes
      previously not found to be involved in s-triazine metabolism. The gene from
      Rhizobium leguminosarum bv. viciae strain 3841 encoding biuret hydrolase was
      synthesized, transformed into Escherichia coli, and expressed. The enzyme was
      purified and found to be stable. Biuret hydrolase catalyzed the hydrolysis of
      biuret to allophanate and ammonia. The k(cat)/K(M) of 1.7 * 10(5) M(-1)s(-1) and
      the relatively low K(M) of 23 +/- 4 MUM together suggested that this enzyme acts
      uniquely on biuret physiologically. This is supported by the fact that of the 34
      substrate analogs of biuret tested, only two demonstrated reactivity, both at
      less than 5% of the rate determined for biuret. Biuret hydrolase does not react
      with carboxybiuret, the product of the enzyme immediately preceding biuret
      hydrolase in the metabolic pathway for cyanuric acid. This suggests an unusual
      metabolic strategy of an enzymatically-produced intermediate undergoing non
      enzymatic decarboxylation to produce the substrate for the next enzyme in the
      pathway.

PMID- 21897880
TI  - The Year Ahead: An initiative to assess the impact of an intervention "Speaking
      Book" on awareness among the potential participants about clinical trials in
      India.

PMID- 21897881
TI  - Challenges in clinical research.

PMID- 21897882
TI  - Perception of various stakeholders regarding clinical drug trial industry in
      India.
AB  - CONTEXT: Though India has been thought to be an ideal destination for conduct of
      clinical drug trials, other smaller countries seem to be doing better. The pace
      of growth observed during 2005-2009 seems to be plateaued in 2010. AIMS: There is
      an urgent need for introspection and corrective actions. MATERIALS AND METHODS:
      An online survey was conducted among various stakeholders from clinical drug
      trial industry in India regarding their perception about clinical drug trial
      industry in India. Respondents were requested to rate training of investigator
      sites, industry, performance of regulatory, etc. RESULTS: Majority of respondent
      felt that the clinical drug trial industry in India is growing, though India is
      not utilizing its full potential. Lack of trained investigators and delay in
      regulatory approvals came out as biggest hurdles. CONCLUSIONS: Urgent steps need
      to be taken in terms of proper training of all stakeholders. Regulatory bodies
      ought to bring about some radical changes in the system so as to match the other
      competing nations.

PMID- 21897883
TI  - Clinical trials in private clinics.

PMID- 21897884
TI  - Regulations and guidelines governing stem cell based products: Clinical
      considerations.
AB  - The use of stem cells as medicines is a promising and upcoming area of research
      as they may be able to help the body to regenerate damaged or lost tissue in a
      host of diseases like Parkinson's, multiple sclerosis, heart disease, liver
      disease, spinal cord damage, cancer and many more. Translating basic stem cell
      research into routine therapies is a complex multi-step process which entails the
      challenge related to managing the expected therapeutic benefits with the
      potential risks while complying with the existing regulations and guidelines.
      While in the United States (US) and European Union (EU) regulations are in place,
      in India, we do not have a well-defined regulatory framework for "stem cell based
      products (SCBP)". There are several areas that need to be addressed as it is
      quite different from that of pharmaceuticals. These range from establishing batch
      consistency, product stability to product safety and efficacy through pre
      clinical, clinical studies and marketing authorization. This review summarizes
      the existing regulations/guidelines in US, EU, India, and the associated
      challenges in developing SCBP with emphasis on clinical aspects.

PMID- 21897885
TI  - Hybrid approaches to clinical trial monitoring: Practical alternatives to 100%
      source data verification.
AB  - For years, a vast majority of clinical trial industry has followed the tenet of
      100% source data verification (SDV). This has been driven partly by the
      overcautious approach to linking quality of data to the extent of monitoring and
      SDV and partly by being on the safer side of regulations. The regulations
      however, do not state any upper or lower limits of SDV. What it expects from
      researchers and the sponsors is methodologies which ensure data quality. How the
      industry does it is open to innovation and application of statistical methods,
      targeted and remote monitoring, real time reporting, adaptive monitoring
      schedules, etc. In short, hybrid approaches to monitoring. Coupled with concepts
      of optimum monitoring and SDV at site and off-site monitoring techniques, it
      should be possible to save time required to conduct SDV leading to more available
      time for other productive activities. Organizations stand to gain directly or
      indirectly from such savings, whether by diverting the funds back to the R&D
      pipeline; investing more in technology infrastructure to support large trials; or
      simply increasing sample size of trials. Whether it also affects the work-life
      balance of monitors who may then need to travel with a less hectic schedule for
      the same level of quality and productivity can be predicted only when there is
      more evidence from field.

PMID- 21897886
TI  - Negotiation skills for clinical research professionals.
AB  - Negotiation as a skill is a key requirement for each and every job profile where
      dealing with multiple parties is involved. The important focus while negotiating
      should be on the interest then position. Key to every successful negotiation is
      advance planning, preparation, and patience as the objective is to create value
      and establish the terms on which parties with differing and often conflicting
      aims will co-operate. While preparing one should collect facts, know priorities,
      principles, identify common ground, decide on walk-away position, and try and
      identify the next best alternative. Negotiation is a set of skills that can be
      learned and practiced so that your ability to utilize relationship, knowledge,
      money, power, time, and personality to negotiate improves with each negotiation.
      In a successful negotiation, all parties win. Important thing to note is that not
      every negotiation involves money. Anytime you want something from someone else
      and anytime someone wants something from you, you are negotiating. Everything is
      negotiable and every day you negotiate with customers, suppliers, colleagues,
      your wife, and even your children. Negotiation is a game, and like any game it
      has its rules and tactics. Clinical Research professionals deal with various
      parties for different purposes at the same time; hence, they require excellent
      negotiation skills. Project Mangers and Clinical Research Associates are the two
      most important roles in clinical research industry who require negotiation skills
      as they deal with various internal and external customers and vendors.

PMID- 21897887
TI  - Intention-to-treat concept: A review.
AB  - Randomized controlled trials often suffer from two major complications, i.e.,
      noncompliance and missing outcomes. One potential solution to this problem is a
      statistical concept called intention-to-treat (ITT) analysis. ITT analysis
      includes every subject who is randomized according to randomized treatment
      assignment. It ignores noncompliance, protocol deviations, withdrawal, and
      anything that happens after randomization. ITT analysis maintains prognostic
      balance generated from the original random treatment allocation. In ITT analysis,
      estimate of treatment effect is generally conservative. A better application of
      the ITT approach is possible if complete outcome data are available for all
      randomized subjects. Per-protocol population is defined as a subset of the ITT
      population who completed the study without any major protocol violations.

PMID- 21897888
TI  - The other insulin story of 1921.

PMID- 21897889
TI  - Gestational diabetes mellitus: A window of opportunity.

PMID- 21897890
TI  - Intensifying existing premix therapy (BIAsp 30) with BIAsp 50 and BIAsp 70: A
      consensus statement.
AB  - In 2009, consensus guidelines were published on intensification of insulin
      therapy using the premix analog biphasic insulin aspart (BIAsp) 30 in the
      treatment of type 2 diabetes, based on the recommendations of an international,
      independent expert panel. The guidelines included recommendations and titration
      algorithms for intensification from basal insulin once (OD) or twice daily (BID)
      to BIAsp 30 BID, from OD BIAsp 30 to BID, and from BID BIAsp 30 to three times
      daily (TID). Building on these recommendations, the objective was to develop
      similar, simple and effective guidelines for intensification switch from a BIAsp
      30 to a mid-/high-ratio premix regimen for the vast majority of patients with
      type 2 diabetes. A panel of independent experts with extensive clinical
      experience in premix analog therapy met in October 2009 to review the therapeutic
      role of mid- and high-ratio premixes (BIAsp 50 and 70, respectively). The panel
      outlined a series of algorithms for intensifying BIAsp 30 BID and TID with mid
      /high-ratio premixes, along with practical suggestions relating to
      intensification for individual patients. A simple tool to aid dose adjustment was
      also developed. The guidelines suggested here should assist physicians in
      introducing mid-/high-ratio premixes to optimize the insulin therapy of patients
      with type 2 diabetes who are failing to achieve glycemic targets on a BIAsp 30
      BID or TID regimen.

PMID- 21897891
TI  - Gestational diabetes mellitus: Get, set, go From diabetes capital of the world to
      diabetes care capital of the world.
AB  - Screening and diagnosis for gestational diabetes mellitus (GDM) as well as
      interventions for its management evoke considerable controversy. There are
      different types of screening methods: universal or risk-based, one step or two
      step. Different thresholds for diagnosis of GDM have been in vogue. Previous
      definition and diagnostic criteria had no place for diagnosis of overt diabetes
      in pregnancy. Following Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study
      and International Association of Diabetes and Pregnancy Study Groups (IADPSG)
      recommendations, new screening and diagnostic criteria around the world seem to
      be gaining consensus. The present recommendation given by IADPSG for screening
      and diagnosis of diabetes mellitus in pregnancy has two discrete phases. The
      first is detection of women with overt diabetes not previously diagnosed or
      treated outside of pregnancy. Universal early testing in populations is
      recommended at the first prenatal visit. The second phase is a 75-g OGTT at 24-28
      week gestation in all women not previously found to have overt diabetes or GDM.
      ACHOIS and MFMU Network trails have proven benefit in treating hyperglycemias
      less than what is diagnostic for diabetes. DIPSI has shown the alternative way
      for resource-challenged communities. Efforts from all stake holders with interest
      in GDM are required to make the diabetes capital of the world into the diabetes
      care capital of the world.

PMID- 21897892
TI  - Adult hypopituitarism: Are we missing or is it clinical lethargy?
AB  - Hypopituitarism, a disease of varied etiologies, is a serious endocrine illness
      that requires early recognition and prompt treatment to avoid its severe
      deleterious effects. In adults it is often missed due to non-specific symptoms of
      growth hormone deficiency and hypogonadism or mild deficiencies of other
      pituitary hormones. In some it may present with acute onset of symptoms
      suggestive of acute adrenal (corticotropin) insufficiency or symptoms due to mass
      lesion in/or around pituitary. High index of suspicion is required to seek
      hypopituitarism in patients with non-specific symptoms such as fatigue and
      malaise. Treatment of isolated hormone deficiency, partial or panhypopituitarism,
      has gratifying results although they require lifelong treatment and follow-up.

PMID- 21897893
TI  - Role of RANKL-RANK/osteoprotegerin molecular complex in bone remodeling and its
      immunopathologic implications.
AB  - Bone remodeling is a cyclic and continuous physiological process, which ensures
      the conservation and renewal of the bone matrix. Osteosynthesis of the bone
      matrix is achieved by osteoblasts and coordinated within this complex machinery
      of bone remodeling with resorption of extracellular bone matrix performed by
      osteoclasts. The mismatch between the activities of osteoblasts and osteoclasts
      has immunopathologic implications associated with either a decrease or increase
      of bone mass mineral density. The balance of the trimolecular control factor
      complex composed of osteoprotegerin (OPG), RANKL (osteoprotegerin ligand) and
      RANK maintains physiologic bone remodeling. This trimolecular complex functions
      as receptors and ligands and belongs to the superfamily of tumor necrosis factor
      (TNF). This mini review highlights the complex interplay of the RANKL-RANK/OPG
      axis and their immunopathologic implications in clinical medicine.

PMID- 21897894
TI  - Gaucher's disease.
AB  - Gaucher's disease (GD) is the most common amongst the various disorders
      classified under the lysosomal storage disorders. GD is a model for applications
      of molecular medicine to clinical delineation, diagnosis, and treatment. The
      multiorgan and varied presentation of the disease makes it a challenge to
      diagnose GD early. The advent of enzyme replacement therapy in the early 1990s
      changed the management, and survival, of patients with GD. In addition to this,
      development of substrate reduction, pharmacological chaperone, and gene therapies
      has broadened the horizon for this rare disease. However, in resource-poor
      countries like ours, optimal management is still a distant dream.

PMID- 21897895
TI  - Diagnosis of gestational diabetes mellitus in Asian-Indian women.
AB  - OBJECTIVE: To assess the validity of Diabetes in Pregnancy Study Group India
      (DIPSI) guidelines, a modified version of the WHO criterion to diagnose
      gestational diabetes mellitus (GDM). MATERIALS AND METHODS: A total of 1 463
      consecutive pregnant women in the second and third trimester of pregnancy
      underwent 75 g oral glucose tolerance test (OGTT) and 2-h plasma glucose (PG) was
      measured by the glucose oxidase-peroxidase (GOD-POD) method. GDM was diagnosed
      with 2-h PG >= 7.8 mmol/L (WHO criteria) and the rest were classified as normal
      glucose tolerant (NGT) women. GDM women were advised medical nutrition therapy
      (MNT) for two weeks. Those who failed to reach the target glycemic level of FPG <
      5.0 mmol/L and 2-h PG < 6.67 mmol/L with MNT were advised insulin. All of them
      were followed throughout pregnancy until delivery. Birth weight of 90th
      percentile (> 3.45 kg) in the neonates was considered as macrosomia (primary
      outcome). RESULTS: The mean maternal age and body mass index were 23.60+/-3.32
      years and 21.5+/-4.06 kg/m(2) respectively. The mean gestational age was 27.9+/
      5.56 weeks. DIPSI criterion identified 196 women (13.4%) as GDM and the rest as
      NGT. Insulin was required in 19 (9.7%) women with GDM. Macrosomia was observed in
      9.9% GDM women with intervention and 9.8% in NGT (P = 1.000). CONCLUSION: DIPSI
      criterion is a one step-cost effective and evidence-based procedure to diagnose
      GDM in any socio-economic setting.

PMID- 21897897
TI  - Hyperparathyroidism revisited - Old wine in new bottles!
AB  - AIM: Hyperparathyroidism (HPT) is a condition that occurs due to exacerbated
      activity of the parathyroid glands. According to the etiology it may be primary,
      secondary or tertiary hyperparathyroidism (pHPT, sHPT, tHPT). This is a study
      done to document and evaluate the presentations of primary and secondary HPT,
      with the associated complications and the approach to management in these
      patients, at our hospital. MATERIALS AND METHODS: Twenty-one patients with HPT
      were encountered at Sri Ramachandra Medical College and Research Institute
      between January 2000 and January 2010. Operative notes, histopathology files, and
      medical records were used for the retrospective analysis of the patients with
      HPT. Parathormone, calcium, and phosphate levels were estimated on all the
      patients, to determine the primary or secondary etiology of this endocrine
      abnormality. Furthermore, these patients were subjected to ultrasonography (USG)
      of the neck and Technetium (99 mTc) scan of the neck to identify the parathyroid
      gland. RESULTS: This study revealed that about 76, 19, and 5% of the patients
      suffered from pHPT, sHPT, and tHPT, respectively, with a female preponderance
      (62%).The neoplasm in all patients with pHPT was parathyroid adenoma. The
      patients presented with renal, bony, and menstrual abnormalities. Cases with sHPT
      had a 15 - 20 year history of chronic kidney disease and they subsequently
      developed bony abnormalities. Even as all the patients with pHPT were managed
      with parathyroidectomy, individuals with sHPT were treated conservatively.
      Postoperative features of hypocalcemia were noted in only one patient.
      CONCLUSION: This study re-emphasizes that pHPT is more common and is often due to
      an adenoma. Recent advances in parathormone sampling operatively and minimal
      access surgery, along with accurate and prompt clinical diagnosis, is necessary
      for the cure of these patients presenting with obscure abdominal, bony, and renal
      ailments.

PMID- 21897896
TI  - Gestational diabetes mellitus is rare in primigravida Pakistani women.
AB  - BACKGROUND: Gestational diabetes mellitus is a metabolic disorder defined as
      glucose intolerance with onset or first recognition during pregnancy. Similar to
      other members of the Asian race, Pakistani women are also considered to be at a
      high risk for developing gestational diabetes. MATERIALS AND METHODS: In order to
      better understand whether this heightened risk attributed to race really exists,
      we conducted a prospective study to assess the glycemic status of primigravida
      women presenting to our hospital. RESULTS: The mean age of 135 subjects enrolled
      was 22 (16-31), with 21 (16%), 60 (44%), and 54 (40%) subjects in the first,
      second, and third trimesters of pregnancy, respectively. The mean fasting, 1
      hour, and 2-hour plasma glucose levels were 69.9 mg/dL (3.9 mmol/L), 129 mg/dL
      (7.2 mmol/L), and 103.6 mg/dL (5.76 mmol/L), respectively. Of 135 women, 6 had a
      blood pressure reading >=140/90 mm Hg and only one met the criteria for
      gestational diabetes mellitus. In our study, despite using the newly proposed
      International Association of Diabetes and Pregnancy Study (IADPS) cut-offs for
      diagnosis of gestational diabetes, the incidence rate of gestational diabetes
      mellitus in primigravida was still <1%. CONCLUSION: Larger trials are needed to
      truly assess the disease burden of gestational diabetes mellitus in Pakistani
      women.

PMID- 21897898
TI  - Autonomic nervous system function in type 2 diabetes using conventional clinical
      autonomic tests, heart rate and blood pressure variability measures.
AB  - BACKGROUND: There are currently approximately 40.9 million patients with diabetes
      mellitus in India and this number is expected to rise to about 69.9 million by
      the year 2025. This high burden of diabetes is likely to be associated with an
      increase in associated complications. MATERIALS AND METHODS: A total of 23 (15
      male and 8 female) patients with type 2 diabetes of 10-15 years duration and
      their age and gender matched controls (n=23) were recruited. All subjects
      underwent detailed clinical proforma, questionnaire related to autonomic
      symptoms, anthropometry, peripheral neural examination and tests of autonomic
      nervous system including both conventional and newer methods (heart rate and
      blood pressure variability). RESULTS: Conventional tests of cardiac
      parasympathetic and sympathetic activity were significantly lower in patients
      with diabetes compared to the controls (P<0.05). The diabetic patients group had
      significantly lower high frequency and low-frequency HRV when expressed in
      absolute units (P<0.05) and total power (P<0.01) compared to the controls.
      CONCLUSION: Data from the current study demonstrated that diabetics had both
      cardiac sympathetic and cardiac parasympathetic nervous system involvement. The
      presence of symptoms and involvement of both components of the autonomic nervous
      system suggest that dysfunction has been present for a while in these diabetics.
      There is a strong need for earlier and regular evaluation of autonomic nervous
      system in type 2 diabetics to prevent further complications.

PMID- 21897899
TI  - Diabetic cardiomyopathy in Manipur.
AB  - OBJECTIVE: To assess the prevalence of diabetic cardiomyopathy in patients with
      diabetes mellitus in Manipur and its correlation with different parameters like
      obesity, blood pressure, lipids, duration of diabetes, and glycemic control.
      MATERIALS AND METHODS: A total of 100 type 2 diabetic patients were selected
      randomly. Anthropometric parameters were recorded, blood glucose levels and lipid
      profiles were determined, and the echocardiographic examinations were performed
      in all patients according to standard techniques. Ejection fraction (EF) was
      calculated by the formula LVEF% = (LVID)2 - (LVIDS)2. Left ventricular EF was
      considered normal when EF was 55 to 75%. Diastolic dysfunction was calculated by
      measuring E and A transmitral inflow velocity. Left ventricular mass in grams is
      calculated by the formula LVM (gm) = 1.04 * 0.8 [(LVID + PWT + IVST)3 - LVID3] +
      0.6. RESULTS AND CONCLUSIONS: Diabetic cardiomyopathy was found in 40 patients
      (40%) of the total study, 29 males (44.6%) and 11 females (31.4%).

PMID- 21897900
TI  - Cushing syndrome and the anesthesiologist, two case reports.
AB  - Cushing's syndrome (CS) is associated with reduced life quality and increased
      mortality, mostly due to cardiovascular disease. The features of this syndrome
      are central obesity, moon facies, facial plethora, supraclavicular fat pads,
      buffalo hump, and purple striae. Other complications include hyperglycemia,
      hypertension, proximal muscle weakness, skin thinning, menstrual irregularities,
      amenorrhea and osteopenia. These make perioperative and anesthetic management
      difficult and present a challenge to the operating team, especially the
      anaesthesiologist. In this paper, we present two such cases of CS, which were
      treated with adrenalectomy. We aim to highlight the special care and precautions
      that need to be taken while administering anesthesia, and in the post operatory
      period. Anaesthesia induction in the two cases of CS was done prior to the
      adrenalectomy procedure and special pre and post operative care was taken.
      Continuous intra operative monitoring of vitals and checking for the stability of
      the haemodynamics was performed. With adequate care and using advanced anesthetic
      techniques, the patients showed uneventful post operative recovery. Though the
      anesthetic management of patients with CS is difficult, desired results can be
      achieved with continuous monitoring and special precautions.

PMID- 21897901
TI  - A rare case of synchronous adrenocortical carcinoma and renal cell carcinoma.
AB  - We present here a rare case of synchronous adrenocortical carcinoma (ACC) and
      renal cell carcinoma (RCC). A 27-year-old woman presented with gradual abdominal
      distension, hematuria, and loss of weight of 3-months duration. She gave a
      history of treatment for hypertension. The computed axial tomography (CT) scan
      revealed a large retroperitoneal mass. Her urinary VMA was slightly elevated. Her
      24-h urinary metanephrine level was normal. The patient underwent left
      adrenalectomy, left nephrectomy, spleenectomy, and distal pancreactomy with
      segmental colonic resection. Postoperative pathology revealed ACC of left
      suprarenal measuring 22 * 19 * 18 cm(3) and RCC involving the left upper pole of
      kidney measuring 3 * 2 * 1 cm(3).

PMID- 21897902
TI  - Adrenocortical carcinoma: Report of two cases.
AB  - Adrenocortical carcinoma (ACC) is a rare neoplasm with a slight predilection for
      female patients. We report two cases of ACC. The first case was of a 7-year-old
      girl who presented with clitoromegaly. The second case was of a 22-Year-old
      female who presented with a lump in the abdomen and features of Cushing's
      syndrome with virilization.The clinical, biochemical, histological features along
      with differential diagnosis are discussed. These cases are presented because of
      their rarity, and also to highlight the importance of differentiating ACC from an
      adenoma particularly in pediatric patients.

PMID- 21897903
TI  - Primary adrenal lymphoma: Differential involvement with varying adrenal function.
AB  - Primary adrenal Non-Hodgkin's lymphoma is rare. The symptoms of the disease and
      response to treatment are variable depending on the type of lymphoma, tumor size,
      and presence of adrenal insufficiency. We report two cases of primary adrenal
      lymphoma who had varied presentations. One presenting with abdominal pain and
      weight loss was documented to have unilateral disease without any adrenal
      insufficiency and showed a good response to combination chemotherapy, while the
      second one had bilateral adrenal involvement with adrenal insufficiency and died
      after second chemotherapy. Functional adrenal involvement in lymphoma depends on
      the extent of involvement; patients with bilateral involvement almost always have
      adrenal insufficiency.

PMID- 21897904
TI  - Unusual presentation of adult Gaucher's disease: A long and difficult road to
      diagnosis.
AB  - Gaucher's disease is the most frequent sphingolipid storage disease. We present a
      case of type 1 non-neuropathic type of adult Gaucher's disease patient with
      atypical presentation.

PMID- 21897905
TI  - AV Gandhi Award for excellence in endocrinology.

PMID- 21897906
TI  - Limit your waist size to half of your height.

PMID- 21897907
TI  - Symptomatic primary hyperparathyroidism in Indians.

PMID- 21897909
TI  - Quality of hypertension care in the family practice center, Aseer Region, Saudi
      Arabia.
AB  - INTRODUCTION: Hypertension (HTN) is a common health problem in Saudi Arabia. Good
      control depends on the quality of care, which should be supervised and monitored
      regularly through clinical audit. AIMS: The objective of this study was to assess
      the quality of HTN care at Al-Manhal Family Practice, Aseer Region, Saudi Arabia.
      SETTINGS AND DESIGN: This study was conductedin 2009 at Al-Manhal Family
      Practice, Aseer Region, Saudi Arabia. MATERIALS AND METHODS: Medical records of
      all hypertensive patients were extracted and reviewed using master sheets.
      Assessment of processes and outcomes of HTN care were based on the standards of
      quality assurance manual issuedby the Ministry of Health. STATISTICAL ANALYSIS
      USED: Data were entered and analyzed by SPPS, version 15. Relevant statistical
      tests were used accordingly and the P-value was considered significant when it
      was less than 0.05. RESULTS: A total of 295 medical records were reviewed and
      assessed. Most patients were Saudi, married, and about 50% were educated. Two
      hundred and thirty-one records were assessed for processes and outcomes of HTN
      care. Weight measurement and physical examination were carried out for 99% and
      97% of the patients, respectively. For 53% of the patients, blood was checked for
      glucose and kidney function and a lipid profile was done. More than two-thirds of
      the patients were overweight and obese while 46% had diabetes. Less than one half
      of the patients had good control of HTN. CONCLUSIONS: By most standards, quality
      of HTN care in Al-Manhal Family Practice was unsatisfactory. Most of the patients
      had comorbidities and poor HTN control. Essential facilities should be provided
      to the practice to optimize HTN care and to improve the degree of control.

PMID- 21897910
TI  - Was there a change in the body mass index of Saudi adolescent girls in Al-Khobar
      between 1997 and 2007?
AB  - BACKGROUND AND OBJECTIVES: Special concern is focused on the nutritional status
      of adolescent girls in order to avoid future health problems. The aim of this
      study was to determine the change in body mass index (BMI) among adolescent Saudi
      girls living in Al-Khobar between 1997 and 2007. MATERIALS AND METHODS: A cross
      sectional sample of adolescent Saudi girls, 15-19-years-old, living in Al-Khobar,
      Saudi Arabia, was analyzed through two data sets. The first data set (n = 400)
      was collected in 1997 and the second (n = 321) was collected in 2007. Both data
      sets used the same sampling method. Anthropometric measurements were made and the
      BMI was used to determine participants' nutritional status. Statistical analysis
      was performed. RESULTS: There was an increase in the median weight of Saudi
      adolescent girls from 1997 to 2007, but the change was not statistically
      significant. There was a statistically significant change, however, in adolescent
      girls' height during the 10-year interval. Using BMI to determine the nutritional
      status of the sample, no statistically significant difference was found.
      Overweight and obesity remain prevalent in about 30% of the adolescent girls, and
      about 3.5% of the girls in both sets were underweight. CONCLUSIONS: This study
      concluded that there was no change in BMI among Saudi adolescent girls living in
      Al-Khobar during the 10-year span. Underweight is of low prevalence, and
      overweight and obesity are the critical nutritional problems that are faced by
      this population. Further research using time span comparisons is important to
      assess changes in maladaptive overweight and obesity.

PMID- 21897911
TI  - Attitudes of Saudi medical students toward the disclosure of information on
      cancer in eastern Saudi Arabia.
AB  - OBJECTIVE: To assess the attitude of future physicians regarding the disclosure
      of diagnosis, prognosis, benefits, and adverse effects of therapeutic
      intervention if they happen to have cancer. It also examined the differences if
      any between regions or gender. MATERIALS AND METHODS: A total of 332 medical
      students from University of Dammam, in the Eastern Province of the Kingdom of
      Saudi Arabia were surveyed using a self-administered questionnaire. The
      questionnaire consisted of nine questions on the attitudes to disclosure of
      information on cancer. This self-administered questionnaire was completed by the
      students in the presence of an investigator. RESULTS: The vast majority of Saudi
      medical students stated that they would like to know about diagnosis of cancer
      (92.8%) and only 7.2% wanted information withheld from them. Further, 67% of the
      males and 74.1% of the females wanted family members to know (P = 0.01), but one
      third (33%) did not want their family to know. Only 24.1% of the male and 21.1%
      of female students wanted their friends to know. In addition, -97% of the males
      and 98.8% of the females wanted to know the diagnosis, and 97% and 95.8% of
      females and males, respectively, would like to know the side effects of the
      therapy. Almost 95% of male and 93.4% of female students wanted to know the
      prognosis. Also, 98% of medical students from the Eastern Region would want the
      diagnosis of cancer to be disclosed compared to 73.6% of those from other regions
      (P = 0.01). There is no difference between the genders in attitudes toward the
      disclosure of the diagnosis, 94.6% and 92.2% (P = 0.38). CONCLUSIONS: There was a
      consensus among Saudi medical students on the knowledge of the benefits of
      treatment, adverse effects of therapy, and prognosis. Female students
      significantly more than males would like their families to be informed.
      Significantly more medical students from the Eastern Region than those from other
      regions would like the diagnosis of cancer to be disclosed.

PMID- 21897912
TI  - Overweight and obesity among school-going children of Lucknow city.
AB  - BACKGROUND: Childhood obesity is increasingly being observed with changing
      lifestyles of families. The magnitude of overweight ranges from 9% to 27.5% and
      obesity ranges from 1% to 12.9% among Indian children. OBJECTIVES: The present
      study was undertaken to study the magnitude of overweight/obesity and its
      determinants among children in Lucknow city. MATERIALS AND METHODS: A list of
      government and private school was procured from Office of Basic Shiksha Adhikari.
      Three government and three private schools were selected by Simple Random
      Sampling. Students of 5th to 12th grades available at the time of study were
      included as study unit. Predesigned and pretested questionnaire was used to
      elicit the information on family characteristics and individual characteristics.
      Height and weight were measured and BMI was calculated. Children with BMI of 25
      and above were considered overweight and children with BMI more than 30 were
      considered obese. RESULTS: Overweight and obesity was found to be 4.17% and
      0.73%, respectively; they together constitute 4.91% for overweight/obesity. The
      study revealed that the important correlates of overweight/obesity were father's
      education, father's occupation, class, children playing outdoor games for less
      than 30 min, and those consuming fast foods. CONCLUSIONS: Children of higher
      classes (above 8th standard) belonging to higher socioeconomic group with less
      outdoor activities and consuming fast foods were more predisposed to
      overweight/obesity. As a preventive strategy, there is a need to apply health and
      nutritional education programs for inculcating healthy life styles, and
      incorporating more outdoor activities in Physical Education Department of school
      curriculum.

PMID- 21897913
TI  - Smoking pattern among female college students in Dammam, Saudi Arabia.
AB  - BACKGROUND: Smoking is the most important avoidable cause of premature morbidity
      and mortality in the world. The estimated annual death rate of 4.9 million people
      in 1999 is expected to rise to 10 million by the 2020s and 2030s, 7 million of
      which will occur in developing countries. AIM: The aim of the present study was
      to estimate the prevalence of smoking and assess its pattern among non-medical
      female college students in Dammam, Saudi Arabia. MATERIALS AND METHODS: A cross
      sectional study was conducted of 1020 female students selected from the
      literature and science colleges by multi-stage stratified random sampling
      technique with proportional allocation. Data were collected using a self
      administered modified WHO Global Youth Tobacco Survey questionnaire. RESULTS:
      Results revealed that occurrence of smoking among female college students was
      8.6%. It was significantly higher among literature college students (12.1%) than
      among Science College students (3.4%). The mean age at which smoking started was
      16 +/- 2.4 years, with a minimum of 11 years. More than half of the students who
      smoked were cigarette smokers, while 43.2% were shisha smokers. There was a
      strong relationship between parents who smoked and daughters who smoked. The main
      motive for smoking was curiosity (44.3%), followed by relief of tension (26.1%).
      CONCLUSIONS: It may be concluded that smoking is increasing among female college
      students in Saudi Arabia. Accordingly, it is recommended that a preventive
      comprehensive health education program on smoking be initiated for females in
      middle schools, that stricter tobacco control measures be adopted by the
      government, and that anti-smoking clinics be established in colleges.

PMID- 21897914
TI  - Toward smoke-free homes: A community-based study on initiatives of rural Indian
      women.
AB  - CONTEXT: Since the home is the primary source of exposure of children to second
      hand smoke (SHS), measures to restrict smoking at home should be introduced to
      protect children from its adverse health consequences. AIMS: Objectives of the
      study were to assess the level of awareness of rural Indian women on the health
      impacts of SHS on children and to look into the strategies they used to reduce
      children's exposure to SHS at home. MATERIALS AND METHODS: A community-based
      cross-sectional study was conducted among 438 rural women using a survey
      questionnaire. Information on socio-demographic characteristics, knowledge on
      specific health effects of SHS on children, and attitude toward having a smoke
      free home were collected. The perceived reasons that made it difficult to have
      smoke-free homes were also explored. RESULTS: A total of 75.8% of women agreed
      that SHS was a serious health risk for children. Knowledge on health impacts of
      SHS on children identified asthma as the most common problem. Smoking by husbands
      (89.7%) was the major source of exposure to SHS at home. While 67.6% of women
      reported having taken measures to limit SHS exposure in their homes, only 12.8%
      of them had tried to introduce a complete ban on smoking at home. On a five-point
      evaluation scale, 73.3% of the women indicated a failure of their initiatives to
      have smoke-free homes. CONCLUSIONS: Women's initiatives to introduce restrictions
      on smoking at home had very limited success and did not produce an appreciable
      change in smoking behavior at home. Lack of empowerment of women in rural India
      probably rendered the interventional measures ineffective.

PMID- 21897915
TI  - Breastfeeding practices: Positioning, attachment (latch-on) and effective
      suckling - A hospital-based study in Libya.
AB  - PURPOSE/OBJECTIVE: To assess the correct position, attachment and effective
      suckling in the breastfeeding of infants as practiced by mothers attending
      hospitals at Benghazi. MATERIALS AND METHODS: An observational, descriptive,
      cross-sectional study was done at AlJamahiriya and AlFateh Hospital in Benghazi,
      Libya, from November 2009 to February 2010. One hundred ninety-two mother-neonate
      units were observed for mother's and baby's position, attachment and effective
      suckling using WHO B-R-E-A-S-T- Feed observation form. Grading of positioning,
      attachment and suckling was done according to the score of various
      characteristics. Data thus collected were analyzed using software SPSS 11.5
      version. RESULTS: About 15% of the infants were about a week old (early neonatal
      period) and 85% were in the late neonatal period. There was poorer positioning
      among primipara (24.0%) than multipara (8.9-12.5%)mothers. Poorer attachment was
      also more evident among primipara (30.0%) compared to multipara (20.9%) mothers.
      Parity was significantly associated with poor position (P = 0.028) and attachment
      (P = 0.002). Poor attachment was related to cracked nipples and mastitis. Preterm
      and low birth weight were significantly associated with poor attachment and poor
      effective suckling. Poor suckling was more (42.8%) in the early neonatal period
      than late neonatal period (32.9%). CONCLUSIONS AND RECOMMENDATIONS: Young (<20
      years) and primipara mothers were more in need of support and guidance for
      appropriate breastfeeding techniques. It is recommended that each mother should
      be observed for mother's and infant's positioning and attachment at the onset of
      breastfeeding and if needed subsequent counseling should be given on correct
      positioning and attachment.

PMID- 21897916
TI  - Clinical characteristics of patients with atrial fibrillation at a tertiary care
      hospital in the central region of Saudi Arabia.
AB  - OBJECTIVE: To report on the clinical presentation, etiology, and laboratory
      features of acute and chronic atrial fibrillation (AF) in a tertiary hospital in
      Riyadh, Saudi Arabia. MATERIALS AND METHODS: We retrospectively studied records
      of 720 patients with AF seen in outpatients and inpatients departments at King
      Abdulaziz Medical City, Riyadh, during the period of 1 January 2002 to 31 August
      2008. RESULTS: Documented acute and chronic AF was present in 157 (21.8%) and 563
      (78.1%) patients, respectively. Palpitations, dizziness and syncope were the most
      frequent symptoms in acute AF, while dyspnea and palpitations were the most
      common symptoms in the chronic type. Acute respiratory problems and acute
      myocardial infarction were significantly more common in acute AF, while
      congestive heart failure and acute respiratory problems (chest infection,
      bronchial asthma, and pulmonary embolism) were significantly more common in
      chronic AF. The most common causes of both types of AF were diabetes mellitus
      (DM) in 68.8%, hypertension (HTN) in 59.3%, chronic lung diseases (bronchial
      asthma, chronic obstructive pulmonary disease and interstitial lung disease) in
      31.8%, valvular heart disease in 23.6%, and ischemic heart disease (IHD) in
      23.1%. In 9 (1.3%) patients, no cause was detected. The echocardiographic
      findings of left ventricular hypertrophy, valve lesions, and depressed left
      ventricular function were significantly more common in chronic AF (P<0.01).
      CONCLUSIONS: Nowadays, DM, HTN, and IHD are becoming the most common predisposing
      factors for AF in the central region of Saudi Arabia and require prevention and
      control.

PMID- 21897917
TI  - Breast abscess caused by penicillin resistant Pneumococci.
AB  - Breast abscess is mostly caused by Staphylococcus aureus. A 26-year-old
      immunocompetent lady was admitted with breast abscess. Incision and drainage
      (I/D) was done and Pneumococci were isolated from the drained pus. The patient
      was earlier treated with Augmentin which was later changed to linezolid after
      testing for antibiotic susceptibility. This strain showed a high level of
      resistance to penicillin. It had been noticed that there was a slow increase in
      the number of penicillin resistant Pneumococci isolated in our hospitals. The
      increase in penicillin-resistant Pneumococci correlates with the intensive use of
      beta-lactam antibiotics. Hence, antibiotics should be used judiciously, avoiding
      their use particularly in mild self-limiting upper respiratory infections.
      Attention therefore, should focus on monitoring resistance in Pneumococci to
      prevent mortality and morbidity associated with this organism, which continues to
      take a heavy toll on children and the elderly.

PMID- 21897918
TI  - A cross-sectional study of the sociodemographic profile of juveniles under
      institutional care in the city of Mumbai.
AB  - OBJECTIVES: To study the sociodemographic profiles of children under
      institutional care, identify the characteristic features of the families prone to
      have destitute children, and suggest measures for prevention of destitution of
      children in the community. MATERIAL AND METHODS: A questionnaire-based cross
      sectional study was conducted in a population of 507 boys and girls from 6 to 18
      years admitted to four different institutes for care and support. A sample of 170
      children was selected using systematic random sampling technique. A survey was
      done to study the health status of the children. Data was analyzed using SPSS
      software. Frequency and proportion were calculated and chi square test was used.
      P value of >0.05 was considered significant. RESULTS: 65.9% of children were in
      the 6 to 12 age group. 63.5% were Hindu by religion. The majority i.e., 80.9% of
      the boys and 80% of the girls were urban in origin, 82.4% of the juveniles were
      from nuclear families, 40.0% of boys and 62.3% of the girl juveniles were from
      lower socioeconomic status. 75% of boys and 25% of the girls had been child
      laborers just before institutionalization. Only 12.7% of juveniles were from
      large families, the rest, the majority (87.3%) were from medium to small sized
      families. CONCLUSIONS: Nuclear families of medium to small size which belong to
      the lower socioeconomic status and of urban origin were found to be unable to
      provide care and support to their children putting them at the risk of becoming
      destitute.

PMID- 21897919
TI  - An epidemiological study of obesity in a rural area.

PMID- 21897920
TI  - Mesoporous silica functionalized with an AIE luminogen for drug delivery.
AB  - An aggregation-induced emission (AIE) luminogen, tetraphenylethene, has been
      successfully grafted onto mesoporous silica SBA-15 for the first time. The
      materials emit blue light upon UV irradiation, and are photostable for the
      ibuprofen (IBU) drug loading and release process, indicating their great
      potential for biomedical applications.

PMID- 21897921
TI  - Facile and chemoselective rhodium-catalysed intramolecular hydroacylation of
      alpha,alpha-disubstituted 4-alkylidenecyclopropanals.
AB  - Mild intramolecular hydroacylation of alpha,alpha-disubstituted 4
      alkylidenecyclopropanals has been developed, avoiding decarbonylation and
      affording cycloheptenones in good yields. The reaction is chemoselective in
      favour of the alkylidenecyclopropane moiety when potential alkene or alkyne
      acceptors are tethered to the substrate.

PMID- 21897928
TI  - Dark state vibronic coupling in the A(2Pi) <- X(2Sigma+) band of ethynyl radical
      via high resolution infrared absorption spectroscopy.
AB  - The high resolution infrared spectrum for the A ((2)Pi) <- X ((2)Sigma(+)) origin
      band of jet-cooled ethynyl radical (C(2)H) in the gas phase is reported, which
      exhibits a strong, parity-specific local perturbation in the upper (2)Pi(1/2)
      state. Based on revised parity assignments of the levels, the perturbing state is
      unambiguously determined to be (2)Sigma(+) symmetry, and thus coupled to the A
      ((2)Pi) state by DeltaK = +/-1 Coriolis interactions. By incorporating Sigma-Pi
      Coriolis coupling into the unperturbed Hamiltonian (containing only rotational,
      spin-rotational, spin-orbit, and lambda-doubling contributions), we are now able
      to fit the observed (2)Pi-(2)Sigma(+) origin band to a sub Doppler experimental
      uncertainty of 15 MHz (0.0005 cm(-1)). In addition, the observation of pairs of
      transitions to mixed states permits determination of the band origin (nu(pert))
      and rotational constant (B(pert)) for the "dark"(2)Sigma(+) state, which prove to
      be in remarkably quantitative agreement with full vibronic predictions of Tarroni
      and Carter as well as UV dispersed fluorescence studies of Hsu et al. This
      represents an important benchmark in mapping out non-Born-Oppenheimer vibronic
      interactions and energy level structure in a polyatomic combustion radical
      system, an understanding of which will be key to modeling chemical reactions in
      both terrestrial and astronomical environments.

PMID- 21897926
TI  - Diastereoselective one-pot Wittig olefination-Michael addition and olefin cross
      metathesis strategy for total synthesis of cytotoxic natural product (+)
      varitriol and its higher analogues.
AB  - A stereoselective route for the total synthesis of anticancer marine natural
      product (+)-varitriol (1) is detailed herein. The impressive biological activity
      and interesting structural features of natural (+)-varitriol fuelled us to
      undertake the synthesis of some higher analogues (1a-j) of this molecule. The key
      features of the synthetic strategy include one-pot Wittig olefination followed by
      a highly diastereoselective oxa-Michael addition to assemble stereochemically
      pure tetrasubstituted THF moiety of the natural varitriol and olefin cross
      metathesis to couple the aromatic part with tetrasubstituted THF moiety. The
      total synthesis of title natural product is efficient with 21.8% overall yield
      for 9 linear steps from D-ribose and thus facilitates the more scaled-up
      practical route for the synthesis of 1 and its analogues as well. The synthetic
      (+)-varitriol (1) and its analogues were screened for their cytotoxicity. The
      present synthetic approach paves the way for preparation of numerous analogues of
      the title natural product for drug development.

PMID- 21897927
TI  - J-coupling constants for a trialanine peptide as a function of dihedral angles
      calculated by density functional theory over the full Ramachandran space.
AB  - We present 13 (3)J, seven (2)J and four (1)J coupling constants (24 in all)
      calculated using B3LYP/D95** as a function of the phi and psi Ramachandran
      dihedral angles of the acetyl(Ala)(3)NH(2) capped trialanine peptide over the
      entire Ramachandran space. With the exception of three of these J couplings, all
      show significant dependence upon both dihedral angles. For each J coupling
      considered, a two dimensional grid with respect to phi and psi angles can be used
      to interpolate the values for any pair of phi and psi values. Such simple
      interpolation is shown to be very accurate. Most of these calculated J couplings
      should prove useful for improving the accuracy of the determination of peptide
      and protein structures from NMR measurements in solution over that provided by
      the common procedure of treating the J couplings as functions of a single
      dihedral angle by means of Karplus-type fittings.

PMID- 21897929
TI  - Chemical bonding and properties of "layered" quaternary antimonide oxide REOZnSb
      (RE = La, Ce, Pr, Nd).
AB  - An efficient route to construct a three-dimensional crystal structure is stacking
      of two-dimensional building blocks (2D-BBs). The crystal structures of potential
      thermoelectric compounds REOZnSb (RE = La, Ce, Pr, Nd) were virtually constructed
      from insulating [REO] and conducting [ZnSb] layers. Further optimizations
      performed by means of first-principles calculations show that REOZnSb should
      exhibit semimetal or narrow band-gap semiconductor behaviors, which is a
      prerequisite for high thermoelectric efficiency. The analysis of the electron
      localizability indicator for LaOZnSb reveals mostly covalent polar interactions
      between all four kinds of atoms. The electron density yields completely balanced
      ionic-like electronic formula La(1.7+)O(1.2-)Zn(0.4+)Sb(0.9-). Furthermore, the
      samples of REOZnSb have been synthesized via solid-state reaction, and their
      crystal structures were confirmed by powder X-ray diffraction. The differences in
      cell parameters between the theoretically optimized and the experimental values
      are smaller than 2%. The temperature dependence of the magnetic susceptibility
      shows that LaOZnSb is diamagnetic above 40 K, whereas CeOZnSb, PrOZnSb and
      NdOZnSb are Curie-Weiss-type paramagnets. Electrical conductivity and Seebeck
      effect measurements indicate that REOZnSb are p-type semiconductors. A
      considerably high Seebeck coefficient and low thermal conductivity were obtained
      for pure LaOZnSb, but its low electrical conductivity leads to a small ZT. The
      high adjustability of the crystal structure as well as properties by optimization
      of the chemical composition in the compounds REOZnSb provide good prospects for
      achieving high thermoelectric efficiency.

PMID- 21897930
TI  - Fine-tuning of lanthanide-monocarboxylate coordination networks through ligand
      decoration.
AB  - We report herein five new coordination polymers of general formula
      [LnNa(C(6)H(5)CO(2))(4)] where Ln = Y (6), Tb (7), Er (8),
      [DyNa(CH(3)CO(2))(4)(MeOH)] (9) and [DyNa(C(3)H(7)CO(2))(4)] (10). Single crystal
      structure analyses revealed that all compounds have a repeating unit containing
      one Ln(3+), one Na(+) and four monocarboxylate ligands (RCO(2)(-)) (R = -CH(3), 
      C(3)H(7), -C(6)H(5)). Compounds 6-8 and 10 possess helical polymeric structures
      which are extended in three dimensions forming chiral srs networks whilst
      compound 9 constitutes a two dimensional honeycomb network, illustrating that
      variation in the alkyl group of the monocarboxylate can result in versatile and
      variable polymeric networks. The magnetic properties of the reported compounds
      have also been studied.

PMID- 21897931
TI  - Can a meso-type dinuclear complex be chiral?: dinuclear beta-diketonato Ru(III)
      complexes.
AB  - Dinuclear Ru(III) complexes, [Ru(III)(acac)(2)(dabe)Ru(III)(acac)(2)] (acacH =
      acetylacetone; dabeH(2) = 1, 2-diacetyl-1,2-dibenzoylethane) and
      [Ru(III)(acac)(2)(tbet)Ru(III)(acac)(2)] (tbetH(2) = 1,1,2,2-tetrabenzoylethane)
      were synthesized by reacting [Ru(acac)(2)(CH(3)CN)(2)]PF(6) with dabeH(2) and
      tbetH(2) respectively, in toluene. The X-ray structural analysis of a meso-type
      dinuclear Ru(III) complex, DeltaLambda-[Ru(III)(acac)(2)(dabe)Ru(III)(acac)(2)],
      showed that the bridging part became chiral due to the orthogonal twisting of two
      non-symmetrical beta-diketonato moieties. To confirm this conclusion, the complex
      was resolved chromatographically to provide a pair of optical antipodes. Such
      chirality in the bridging part was not generated for
      [Ru(III)(acac)(2)(tbet)Ru(III)(acac)(2)], because the beta-diketonato moieties in
      tbet(2-) are symmetrical.

PMID- 21897932
TI  - Ionic liquid mediated Cu-catalyzed cascade oxa-Michael-oxidation: efficient
      synthesis of flavones under mild reaction conditions.
AB  - Flavonoids are a class of natural products, found in a wide range of vascular
      plants and dietary components. Their low toxicity and extensive biological
      activities, including anti-cancer and anti-bacterial, have made them attractive
      candidates to serve as therapeutic agents for many diseases. Herein, we disclose
      a highly efficient synthetic method of CuI-catalyzed cascade oxa-Michael
      oxidation, using chalcones as substrates, mediated by the ionic liquid
      [bmim][NTf2] at a low temperature. This efficient synthetic method has
      demonstrated high synthetic utility and can afford flavones in good to high
      yields (up to 98%).

PMID- 21897933
TI  - Light-activated gating and permselectivity in interfacial architectures combining
      "caged" polymer brushes and mesoporous thin films.
AB  - We demonstrate that "caged" macromolecular building blocks can endow mesoporous
      thin films with light responsiveness and lead to the creation of functional
      hybrid ensembles with phototriggered permselective properties.

PMID- 21897934
TI  - Metal flux through consuming interfaces in ligand mixtures: boundary conditions
      do not influence the lability and relative contributions of metal species.
AB  - In a mixture of metal ions and complexes, it is difficult to predict ecological
      risk without understanding the contribution of each metal species to biouptake.
      For microorganisms, the rate of uptake (internalization flux) has not only a
      major influence on the total metal flux but also on the bioavailability of the
      various metal species and their relative contributions to the total flux. In this
      paper, the microorganism is considered as a consuming interface, which interacts
      with the metal ion, M, via the Michaelis-Menten boundary conditions. The
      contribution of each metal complex to the overall metal flux, in relation to its
      lability, is examined for a number of important boundary parameters (the
      equilibrium constant K(a) of metal with transport sites, internalization rate
      constant k(int) and total transport sites concentration {R}(t)). Computations
      were performed for Cu(II) complexes, in a multicomponent culture medium for
      microoganisms. For a one-ligand system, results were acquired using rigorous
      mathematical expressions, whereas approximate expressions, based on the reaction
      layer approximation (RLA) and rigorous numerical computations (computer codes
      MHEDYN and FLUXY), were employed for ligand mixtures. Under the condition of
      ligand excess, as often found in the natural environment, the relative
      contribution of each metal species to the total flux is shown to be independent
      of the boundary conditions. This finding has important implications, including an
      improved basis for relating the analytical signals of dynamic metal speciation
      sensors to metal bioavailability.

PMID- 21897935
TI  - The effect of lipid oxidation on the water permeability of phospholipids
      bilayers.
AB  - The effect of lipid oxidation on water permeability of phosphatidylcholine
      membranes was investigated by means of both scattering stopped flow experiments
      and atomistic molecular dynamics simulations. Formation of water pores followed
      by a significant enhancement of water permeability was observed. The molecules of
      oxidized phospholipids facilitate pore formation and subsequently stabilize water
      in the membrane interior. A wide range of oxidation ratios, from 15 to 100 mol%,
      was considered. The degree of oxidation was found to strongly influence the time
      needed for the opening of a pore. In simulations, the oxidation ratio of 75 mol%
      was found to be a threshold for spontaneous pore formation in the tens of
      nanosecond timescale, whereas 15 mol% of oxidation led to significant water
      permeation in the timescale of seconds. Once a pore was formed, the water
      permeability was found to be virtually independent of the oxidation ratio.

PMID- 21897936
TI  - Microsolvation of Co2+ and Ni2+ by acetonitrile and water: photodissociation
      dynamics of M(2+)(CH3CN)n(H2O)m.
AB  - The microsolvation of cobalt and nickel dications by acetonitrile and water is
      studied by measuring photofragment spectra at 355, 532 and 560-660 nm. Ions are
      produced by electrospray, thermalized in an ion trap and mass selected by time of
      flight. The photodissociation yield, products and their branching ratios depend
      on the metal, cluster size and composition. Proton transfer is only observed in
      water-containing clusters and is enhanced with increasing water content. Also,
      nickel-containing clusters are more likely to undergo charge reduction than those
      with cobalt. The homogeneous clusters with acetonitrile M(2+)(CH(3)CN)(n) (n = 3
      and 4) dissociate by simple solvent loss; n = 2 clusters dissociate by electron
      transfer. Mixed acetonitrile/water clusters display more interesting dissociation
      dynamics. Again, larger clusters (n = 3 and 4) show simple solvent loss. Water
      loss is substantially favored over acetonitrile loss, which is understandable
      because acetonitrile is a stronger ligand due to its higher dipole moment and
      polarizability. Proton transfer, forming H(+)(CH(3)CN), is observed as a minor
      channel for M(2+)(CH(3)CN)(2)(H(2)O)(2) and M(2+)(CH(3)CN)(2)(H(2)O) but is not
      seen in M(2+)(CH(3)CN)(3)(H(2)O). Studies of deuterated clusters confirm that
      water acts as the proton donor. We previously observed proton loss as the major
      channel for photolysis of M(2+)(H(2)O)(4). Measurements of the photodissociation
      yield reveal that four-coordinate Co(2+) clusters dissociate more readily than
      Ni(2+) clusters whereas for the three-coordinate clusters, dissociation is more
      efficient for Ni(2+) clusters. For the two-coordinate clusters, dissociation is
      via electron transfer and the yield is low for both metals. Calculations of
      reaction energetics, dissociation barriers, and the positions of excited
      electronic states complement the experimental work. Proton transfer in photolysis
      of Co(2+)(CH(3)CN)(2)(H(2)O) is calculated to occur via a (CH(3)CN)Co(2+)-OH(-)
      H(+)(NCCH(3)) salt-bridge transition state, reducing kinetic energy release in
      the dissociation.

PMID- 21897937
TI  - Structure and cation ordering in spinel-type TcCo2O4. An example of a trivalent
      technetium oxide.
AB  - The structure of TcCo(2)O(4) has been determined using a combination of
      synchrotron X-ray and neutron powder diffraction methods. It has an inverse
      spinel structure where the Tc occupies the octahedral sites. Both the refined Tc
      O distance and X-ray absorption spectra suggest the Tc is predominantly
      trivalent.

PMID- 21897938
TI  - Chemical engineering of Mycobacterium tuberculosis dodecin hybrids.
AB  - The suitability for chemical engineering of the highly symmetrical Mycobacterium
      tuberculosis dodecin was investigated, its inner cavity providing a large
      compartment shields introduced compounds from bulk solvent. Hybrids were obtained
      by S-alkylation of cysteine mutants and characterized by spectroscopic methods,
      including the crystal structures of wild type and biohybrid dodecins.

PMID- 21897939
TI  - Ruthenium(II) polypyridyl complexes as carriers for DNA delivery.
AB  - Two novel water soluble ruthenium(II) complexes [Ru(bpy)(2)(bqbg)](2+) and
      [Ru(phen)(2)(bqbg)](2+) have been structurally characterized and their DNA
      condensation activity, cytotoxicity, and cellular uptake studies of DNA
      condensates as potential non-viral DNA carriers were evaluated.

PMID- 21897940
TI  - Solvent-dependent aggregation behavior of a new Ru(II)-polypyridyl based
      metallosurfactant.
AB  - Variation of the solvent polarity leads to the formation of vesicles and reverse
      vesicles of a newly synthesized amphiphilic Ru(II)-polypyridyl complex.

PMID- 21897941
TI  - Palladium-catalyzed reaction of 2-alkynylhalobenzene with 2-alkynylbenzamide: an
      efficient approach to indeno[1,2-c]azepin-3(2H)-ones.
AB  - A novel and efficient route for rapid access to indeno[1,2-c]azepin-3(2H)-ones is
      described, which proceeds through a palladium-catalyzed tandem reaction of 2
      alkynylhalobenzene with 2-alkynylbenzamide in the presence of PPh(3) or PCy(3).
      The indeno[1,2-c]azepin-3(2H)-ones which incorporate both indene and unsaturated
      seven-membered ring lactam skeletons are obtained in good to excellent yields.

PMID- 21897942
TI  - Reactive uptake of NO3 radicals by unsaturated fatty acid particles.
AB  - The reactive uptake of NO(3) by particles containing four unsaturated fatty acid
      species was studied for the first time in a flow tube reactor coupled to a
      chemical ionization mass spectrometer (CIMS). Using a mixed-phase relative rates
      technique, the reactive uptake coefficients, gamma(part), were determined to be
      (0.27 +/- 0.06) for oleic acid (OA), (0.53 +/- 0.12) for linoleic acid (LA),
      (0.72 +/- 0.17) for linolenic acid (LNA), and (1.01 +/- 0.18) for conjugated
      linoleic acid (CLA) in N(2) bath gas. In the presence of 20% O(2), their uptake
      coefficients are (0.31 +/- 0.09) for OA, (0.55 +/- 0.12) for LA, (0.78 +/- 0.17)
      for LNA, and (1.08 +/- 0.17) for CLA. All the uncertainties are 2sigma and
      represent precision only. The products of the NO(3) reactions with these organic
      particles were studied in the presence and absence of O(2) using CIMS. It was
      found that the detected yields and compositions of the products were
      substantially different with or without O(2). Based on the observed products and
      general gas-phase chemistry of NO(3) radicals, a reaction mechanism is proposed
      for NO(3) reactions with unsaturated organic particles. The atmospheric
      implications of the heterogeneous chemical processes involving NO(3) are also
      discussed.

PMID- 21897943
TI  - Pyrene-cored dendrimer with carbazole derivatives as dendrons: synthesis,
      properties and application in white light-emitting diode.
AB  - A new dendrimer using pyrene as core and carbazole derivative as dendron has been
      successfully prepared via Suzuki coupling reaction. Its chemical structure was
      confirmed through (1)H NMR, elemental analysis and MALDI-TOF MS methods. The
      dendrimer synthesized possessed excellent thermal stability with initial
      decomposition temperature over 470  degrees C and high fluorescence quantum yield
      of 86%. The luminescence spectra showed that, relative to the solution sample,
      the emission peaks of the solid dendrimer film were apparently broadened and red
      shifted, indicating the strong pi-pi stacking effect between the pyrene moieties.
      By doping 1.5% of the dendrimer in 4,4'-bis[N-(1-naphthyl)-N-phenylamino]biphenyl
      (NPB), a light-emitting diode device was fabricated in the ITO/NPB/NPB:dendrimer
      (1.5%)/TPBI/Mg:Ag configuration, which emitted a white color with Commission
      Internationale de L'Eclairage (CIE(x,y)) coordinates of (0.29, 0.34) and a
      maximum brightness of 1300 cd m(-2), exhibiting promising potential in white
      light-emitting diode application.

PMID- 21897944
TI  - Non-monotonic dependence of water reorientation dynamics on surface
      hydrophilicity: competing effects of the hydration structure and hydrogen-bond
      strength.
AB  - The reorientation dynamics of interfacial water molecules was recently shown to
      change non-monotonically next to surfaces of increasing hydrophilicity, with
      slower dynamics next to strongly hydrophobic (apolar) and very hydrophilic
      surfaces, and faster dynamics next to surfaces of intermediate hydrophilicities.
      Through a combination of molecular dynamics simulations and analytic modeling, we
      provide a molecular interpretation of this behavior. We show that this non
      monotonic dependence arises from two competing effects induced by the increasing
      surface hydrophilicity: first a change in the hydration structure with an
      enhanced population of water OH bonds pointing toward the surface and second a
      strengthening of the water-surface interaction energy. The extended jump model,
      including the effects due to transition-state excluded volume and transition
      state hydrogen-bond strength, provides a quasi-quantitative description of the
      non-monotonic changes in the water reorientation dynamics with surface
      hydrophilicity.

PMID- 21897945
TI  - Li mobility in Nasicon-type materials LiM2(PO4)3, M = Ge, Ti, Sn, Zr and Hf,
      followed by 7Li NMR spectroscopy.
AB  - Lithium mobility in LiM(2)(PO(4))(3) compounds, M = Ge and Sn, has been
      investigated by (7)Li Nuclear Magnetic Resonance (NMR) spectroscopy, and deduced
      information compared with that reported previously in Ti, Zr and Hf members of
      the series in the temperature range 100-500 K. From the analysis of (7)Li NMR
      quadrupole interactions (C(Q) and eta parameters), spin-spin T(2)(-1) and spin
      lattice T(1)(-1) relaxation rates, structural sites occupancy and mobility of
      lithium have been deduced. Below 250 K, Li ions are preferentially located at
      M(1) sites in rhombohedral phases, but occupy intermediate M(12) sites between
      M(1) and M(2) sites in triclinic ones. In high-temperature rhombohedral phases, a
      superionic state is achieved when residence times at M(1) and M(12) sites become
      similar and correlation effects on Li motion decrease. This state can be obtained
      by large order-disorder transformations in rhombohedral phases or by sharp first
      order transitions in triclinic ones. The presence of two relaxation mechanisms in
      T(1)(-1) plots of rhombohedral phases has been associated with departures of
      conductivity from the Arrhenius behavior. Long term mobility of lithium is
      discussed in terms of the cation vacancy distribution along conduction paths.

PMID- 21897946
TI  - Complexes in context: attempting to control the cellular uptake and localisation
      of rhenium fac-tricarbonyl polypyridyl complexes.
AB  - Transition metal lumophores are now well established as agents for cell imaging,
      but we are still not able to predict generally and with confidence their cellular
      localisation, or, for that matter, their uptake efficiencies. While many such
      complexes have been shown to illuminate cells, genuine applications in biomedical
      research will only be developed when their uptake and localisation are better
      understood. This perspective is not a comprehensive review of luminescence, but
      is an overview of attempts to control uptake and localisation, focussing on a
      personal account of this group's development of imaging agents based on the
      Re(CO)(3) bipyridine core, and our attempts to understand and control their
      cellular behaviour.

PMID- 21897947
TI  - Zirconia layer coated mesoporous silica microspheres as HILIC SPE materials for
      selective glycopeptide enrichment.
AB  - Characterization of protein glycosylation requires highly specific methods for
      the enrichment of glycopeptides because of their sub-stoichiometric glycosylation
      site occupancy. The hydrophilic affinity based strategy has attracted more
      attention, owing to its broad glycan specificity, good reproducibility, and
      compatibility with mass spectrometric (MS) analysis. Several polar matrices have
      emerged for hydrophilic interaction chromatography (HILIC) approaches, including
      sepharose, cellulose, ZIC-HILIC and titania. Here, we present the solid-phase
      extraction (SPE) utility of zirconia coated mesoporous silica (ZrO(2)/MPS)
      microspheres for glycopeptide isolation prior to MS analysis. The high
      specificity of this SPE approach was demonstrated by the enrichment of
      glycopeptides from the digests of model glycoproteins in HILIC mode. ZrO(2)/MPS
      microspheres show superior selectivity and glycosylation heterogeneity coverage
      for glycopeptide enrichment to conventional sepharose. Furthermore, digested
      mixtures of the phosphoprotein alpha-casein and IgG were also treated with
      ZrO(2)/MPS HILIC SPE materials, which exhibited that glycopeptides could be
      effectively enriched with interference from phosphorylated peptides.

PMID- 21897948
TI  - Sensitive detection of esculetin based on a CdSe nanoparticles-decorated
      poly(diallyldimethylammonium chloride)-functionalized graphene nanocomposite
      film.
AB  - An electrochemical sensor based on a CdSe nanoparticles (NPs)-decorated
      poly(diallyldimethylammonium chloride) (PDDA)-functionalized graphene (CdSe-PDDA
      G) nanocomposite was fabricated for the sensitive detection of esculetin. The
      nanocomposite was characterized by X-ray diffraction (XRD), ultraviolet/visible
      spectra (UV-vis) and transmission electron microscopy (TEM). Cyclic voltammetry
      (CV) and differential pulse voltammetry (DPV) were used to investigate the
      electrochemical behaviors of esculetin on the CdSe-PDDA-G composite film-modified
      glassy carbon electrode (GCE). The experimental results indicated that the
      incorporation of CdSe NPs with PDDA-G greatly enhanced the electrochemical
      response of esculetin. This electrochemical sensor displayed satisfactory
      analytical performance for esculetin detection over a range from 1.0 * 10(-8) to
      5.0 * 10(-5) mol L(-1) with a detection limit of 4.0 * 10(-9) mol L(-1) (S/N =
      3). Moreover, the sensor also exhibited good reproducibility and stability, and
      could be used for the detection of esculetin in real samples with satisfactory
      results.

PMID- 21897949
TI  - A novel microreactor approach for analysis of ketones and aldehydes in breath.
AB  - We report a fabricated microreactor with thousands of micropillars in channels.
      Each micropillar surface is chemically functionalized to selectively
      preconcentrate gaseous ketones and aldehydes of exhaled breath and to enhance
      ultra-trace, rapid analysis by direct-infusion Fourier transform-ion cyclotron
      resonance (FT-ICR) mass spectrometry (MS). The micropillar reactive coating
      contains the quaternary ammonium aminooxy salt 2-(aminooxy)ethyl-N,N,N
      trimethylammonium iodide (ATM) for capturing trace carbonyl VOCs by means of an
      oximation reaction. We demonstrate the utility of this approach for detection of
      C(1) to C(12) aldehydes and ketones in exhaled breath, but the approach is
      applicable to any gaseous sample.

PMID- 21897950
TI  - Growth and restoration of a T-tile-based 1D DNA nanotrack.
AB  - We designed an artificial one-dimensional DNA nanotrack that contains two T
      motifs. It can be fabricated in a free solution and with a mica-assisted growth
      process. Also, we introduced a dry and wet method for the restoration of DNA
      nanostructures in order for them to be used in multiple applications.

PMID- 21897951
TI  - Diverse organo-peptide macrocycles via a fast and catalyst-free oxime/intein
      mediated dual ligation.
AB  - Macrocyclic Organo-Peptide Hybrids (MOrPHs) can be prepared from genetically
      encoded polypeptides via a chemoselective and catalyst-free reaction between a
      trifunctional oxyamino/amino-thiol synthetic precursor and an intein-fusion
      protein incorporating a bioorthogonal keto group.

PMID- 21897952
TI  - Efficient and highly selective iron-catalyzed reduction of nitroarenes.
AB  - Pyrolysis of iron-phenanthroline complexes supported on carbon leads to highly
      selective catalysts for the reduction of structurally diverse nitroarenes to
      anilines in 90-99% yields. Excellent chemoselectivity for the nitro group
      reduction is demonstrated.

PMID- 21897953
TI  - High adsorptive gamma-AlOOH(boehmite)@SiO2/Fe3O4 porous magnetic microspheres for
      detection of toxic metal ions in drinking water.
AB  - gamma-AlOOH(boehmite)@SiO(2)/Fe(3)O(4) porous magnetic microspheres with high
      adsorption capacity toward heavy metal ions were found to be useful for the
      simultaneous and selective electrochemical detection of five metal ions, such as
      ultratrace zinc(II), cadmium(II), lead(II), copper(II), and mercury(II), in
      drinking water.

PMID- 21897954
TI  - Fluorescence detection of coralyne and polyadenylation reaction using an
      oligonucleotide-based fluorogenic probe.
AB  - This study describes the development of a simple, sensitive, and selective
      detection system for coralyne and polyadenylation reaction based on the fact that
      coralyne induces a conformational change of the polyadenosine [poly(A)]
      oligonucleotide through A-coralyne-A coordination, thereby enhancing the
      fluorescence of SYBR Green I.

PMID- 21897955
TI  - Highly tunable arylated cinchona alkaloids as bifunctional catalysts.
AB  - We report the design and evaluation of a library of chiral bifunctional
      organocatalysts in which the distance between the catalytically active units can
      be systematically varied.

PMID- 21897957
TI  - Pillared graphene as a gas separation membrane.
AB  - Graphene and carbon nanotubes are considered as future materials in various
      fields, including adsorption, accumulation and separation processes, and so are
      hybrid materials combining their properties. This paper reports our study on
      separative abilities of 3-D network structures consisting of graphene planes
      pillared with nanotube fragments. Results of molecular dynamics simulations
      confirm that such materials can be successfully applied as membranes in relation
      to noble gas mixtures. A simple explanation of the mechanism underlying the
      process is proposed.

PMID- 21897958
TI  - Protein coverage on polymer nanolayers leading to mesenchymal stem cell
      patterning.
AB  - Interactions of gelatin and albumin with a photo-reactive diphenylamino-s
      triazine bridged p-phenylene vinylene polymer (DTOPV) were examined by using
      surface plasmon resonance (SPR) spectroscopy to explore the effect of the polymer
      structure on protein coverage of DTOPV nanofilms. The SPR data revealed a
      significant increase of gelatin adsorption on UV-DTOPV nanofilms, while the
      adsorption of albumin was decreased by UV exposure in the time frame of the
      experiment. We also found that the selective adsorption of these proteins was
      highly dependent on the protein concentration; the highest selectivity of protein
      adsorption was obtained at the lowest concentration (3.5 MUg ml(-1)), while no
      selective adsorption was confirmed at high concentrations (350 and 1000 MUg ml(
      1)). The selective attachment of mesenchymal stem cells (MSCs) was directly
      correlated with the selective adsorption of these proteins onto DTOPV nanofilms.
      The MSCs attachment onto UV-DTOPV films was promoted with only small mass
      coverage of gelatin, which led to MSC patterning onto the patterned DTOPV
      nanofilms successfully. The role of cell adhesion proteins that we found in this
      study will be a clue to elucidate the complex response of biomolecules on
      functional polymer nanolayers, and contribute to build up biocompatible surfaces
      on various advanced materials for the sake of cell engineering and medical
      implants.

PMID- 21897959
TI  - Amino acid-based ionic liquids: using XPS to probe the electronic environment via
      binding energies.
AB  - Here we report the synthesis and characterisation by X-ray photoelectron
      spectroscopy (XPS) of eight high purity amino acid-based ionic liquids (AAILs),
      each containing the 1-octyl-3-methylimidazolium, [C(8)C(1)Im](+), as a standard
      reference cation. All expected elements were observed and the electronic
      environments of these elements identified. A fitting model for the carbon 1s
      region of the AAILs is reported; the C aliphatic component of the cation was used
      as an internal reference to obtain a series of accurate and reproducible binding
      energies. Comparisons are made between XP spectra of the eight AAILs and selected
      non-functionalised ionic liquids. 1-octyl-3-methylimidazolium acetate was also
      studied as a model of the carboxyl containing amino acid anion. The influence of
      anionic substituent groups on the measured binding energies of all elements is
      presented, and communication between anion and cation is investigated. This data
      is interpreted in terms of hard and soft anions and compared to the Kamlet-Taft
      hydrogen bond acceptor ability, beta, for the ionic liquids. A linear correlation
      is presented which suggests that the functional side chain, or R group, of the
      amino acid has little impact upon the electronic environment of the charge
      bearing moieties within the anions and cations studied.

PMID- 21897960
TI  - Role of electromechanical and mechanoelectric effects in protein hydration under
      hydrostatic pressure.
AB  - Recent measurements of lysozyme hydration water density under non-denaturing
      pressure show that it is higher than that of bulk water in the same conditions.
      High protein hydration layer density has earlier been observed at ambient
      conditions and ascribed to electrostriction. We calculate the pressure-induced
      protein mean surface charge density increment Deltasigma. Within the hydration
      layer, the higher fields due to Deltasigma lead to an additional water
      compression via electrostriction. The increment Deltasigma is considered as due
      to a mechanoelectric effect in protein molecules. The mean value of the effective
      mechanoelectric coefficient d is calculated and compared with piezoelectric
      coefficients of amino acids and their compounds.

PMID- 21897961
TI  - Quantitative analysis of high field liquid state Dynamic Nuclear Polarization.
AB  - Dynamic Nuclear Polarization (DNP) in the liquid state has become the focus of
      attention to improve the NMR sensitivity of mass limited samples. The Overhauser
      model predicts a fast reduction in DNP enhancement at high magnetic fields where
      the Electron Larmor frequency exceeds the typical inverse correlation time of the
      magnetic interaction between a radical spin and proton spins of the water
      molecules. Recent experiments have shown that an appreciable DNP enhancement in
      the liquid state is possible also at magnetic fields of 3 to 9 Tesla. At present
      it is not clear whether the Overhauser model needs to be adapted to explain these
      results. In the present paper we aim to resolve this question by a combination of
      in situ temperature dependent NMR relaxation measurements, EPR and DNP
      experiments. Enhancement factors of up to -165 are obtained with microwave powers
      below 500 mW. We conclude that at 3.4 Tesla (95 GHz) the various measurements are
      consistent with each other and in quantitative agreement with Overhauser theory.
      Microwave heating of the sample does play an important role to reduce the
      correlation times and allow a substantial Overhauser DNP. The typical enhancement
      factors may allow new applications in microfluidic NMR.

PMID- 21897962
TI  - Formation of the second superhydrophobic shell around an encapsulated metal ion:
      synthesis, X-ray structure and electrochemical study of the clathrochelate and
      bis-clathrochelate iron(II) and cobalt(II, III) dioximates with ribbed
      perfluoroarylsulfide substituents.
AB  - The nucleophilic substitution of six chlorine atoms of the n-butylboron-capped
      clathrochelate iron and cobalt(II) precursors with perfluoroarylthiolate anions
      afforded the hexaperfluoroarylsulfide macrobicyclic iron and cobalt(II) tris
      dioximates. The complexes obtained are soluble in aromatic and aliphatic
      hydrocarbons as well as in polar aprotonic solvents due to the presence of the
      superhydrophobic fluorine-containing molecular periphery. As it follows from the
      X-ray data for five iron and cobalt mono- and bis-clathrochelates, the geometry
      of their macrobicyclic frameworks is affected by both the nature of an
      encapsulated metal ion and that of the ribbed substituents. Bis-capping fragment
      Co(II)O(6) of the Co(III)Co(II)Co(III) bis-clathrochelate possesses a trigonal
      antiprismatic geometry, all the Co(II)N(6) coordination polyhedra are trigonal
      prismatic, and those of the encapsulated iron(II) and cobalt(III) ions are
      intermediate between them. The wide range of Co-N distances as well as the
      significant shifts of the encapsulated cobalt(II) ions from the centres of their
      N(6)-coordination polyhedra were explained by the Jahn-Teller distortion. The EPR
      and magnetometry data are also characteristic of the low-spin cobalt(II)
      complexes with this distortion. The parameters of the (57)Fe Mossbauer spectra of
      the iron macrobicycles are characteristic of the low-spin iron(II) complexes. The
      cyclic voltammograms (CVs) for the complexes studied contain the one-electron
      oxidation and reduction waves assigned to metal-centered redox-processes. The
      Fe(2+/3+) and Co(2+/3+) oxidations are quasi-reversible or irreversible. The
      anionic clathrochelate species resulting from the reversible Co(2+/+) reductions
      are stable on the CV time scale, whereas their iron(I)-containing analogs are
      unstable.

PMID- 21897963
TI  - Octa- and hexametallic iron(III)-potassium phosphonate cages.
AB  - Two new iron(III)-potassium phosphonate cage complexes with {K(2)Fe(6)} and
      {K(2)Fe(4)} cores are reported. Magnetic studies reveal antiferromagnetic
      interactions between the Fe(III) centres occur in these cages.

PMID- 21897964
TI  - Theoretical study on intramolecular allene-diene cycloadditions catalyzed by
      PtCl2 and Au(I) complexes.
AB  - The intramolecular [4C+3C] cycloaddition reaction of allenedienes catalysed by
      PtCl(2) and several Au(I) complexes has been studied by means of DFT
      calculations. Overall, the reaction mechanism comprises three main steps: (i) the
      formation of a metal allyl cation intermediate, (ii) a [4C(4pi)+3C(2pi)]
      cycloaddition that produces a seven-membered ring and (iii) a 1,2-hydrogen
      migration process on these intermediates. The reaction proceeds with complete
      diastereochemical control resulting from a favoured exo-like cycloaddition.
      Allene substituents have a critical influence in the reaction outcome and
      mechanism. The experimental observation of [4C+2C] cycloadducts in the reaction
      of substrates lacking substituents at the allene terminus can be explained
      through a mechanism involving Pt(IV)-metallacycles. With gold catalysts it is
      also possible to obtain [4C+2C] cycloaddition products, but only with substrates
      featuring terminally disubstituted allenes, and employing pi-acceptor ligands at
      gold. However the mechanism for the formation of these adducts is completely
      different to that proposed with PtCl(2), and consists of the formation of a metal
      allyl cation, subsequent [4C+3C] cycloaddition and a 1,2-alkyl shift (ring
      contraction). Electronic analysis indicates that the divergent pathways are
      mainly controlled by the electronic properties of the gold heptacyclic species (L
      Au-C(2)), in particular, the backdonation capacity of the metal center to the
      unoccupied C(2) (ppi-orbital) of the intermediate resulting from the [4C+3C]
      cycloaddition. The less backdonation, (i.e. using P(OR)(3)Au(+) complexes), the
      more favoured is the 1,2-alkyl shift.

PMID- 21897965
TI  - Unprecedented heptacopper(II) cluster with body-centred anti-prismatic topology.
      Structure, magnetism and density functional study.
AB  - Using a (2-pyridyl)ethylamine-appended carboxylate ligand a new cluster
      [Cu(II)(7)(L)(4)(MU(3)-OH)(2)(H(2)O)(2)(DMF)(2)][ClO(4)](4).4H(2)O (1) [L(2-): N
      {CH(2)CH(2)(2-pyridyl)}(CH(2)CH(2)CO(2))(2)] is synthesized, as a result of
      'coordination-driven self-assembly'. The structure of 1 is unique and consists of
      a centrosymmetric carboxylato- and hydroxo-bridged heptanuclear copper(II)
      cation, with body-centred anti-prismatic topology. The four crystallographically
      independent copper(II) centres differ markedly in their coordination geometry. In
      addition to establishing cluster authenticity, the structural analysis of 1
      discloses two notable features. The existence of {Cu(II)(3)(MU(3)-OH)}(5+) core
      and H-bonded metal-coordinated carboxylate and water unit, with water acting as a
      proton donor. Both of these features have biological implications. Magnetic
      measurements reveal that in this unprecedented cluster the net magnetic-exchange
      is antiferromagnetic. The different types of magnetic-exchange coupling constants
      (J values) considered for magnetic data analysis appear to adopt a variety of
      values depending on the specific geometric parameters associated with two
      interacting copper(II) centres. Notably, for 1 a good agreement between the J
      values obtained from DFT calculations at the B3LYP level of theory and from the
      experimental data is achieved.

PMID- 21897966
TI  - Dietary chromones as antioxidant agents--the structural variable.
AB  - This study reports an evaluation of the free radical scavenging ability of a
      series of chromone derivatives, in the light of their structural features and
      conformational behaviour. The 2,2-diphenyl-1-picrylhydrazyl radical (DPPH) test
      for the assessment of radical scavenging properties was applied, and the
      interpretation of the experimental results was assisted by ab initio theoretical
      approaches that allowed relevant parameters, such as the enthalpy of formation of
      the radical species, to be predicted. From the eighteen tested compounds, three
      fisetin, luteolin and quercetin-are shown to act as effective antiradicals.
      Consistent structure-activity relationships (SARs) were established regarding the
      antioxidant role of this type of chromone-based system.

PMID- 21897967
TI  - Fullerene C60 as a multifunctional system for drug and gene delivery.
AB  - The fullerene family, and especially C(60), has delighted the scientific
      community during the last 25 years with perspective applications in a wide
      variety of fields, including the biological and the biomedical domains. Several
      biomedical uses have been explored using water-soluble C(60)-derivatives.
      However, the employment of fullerenes for drug delivery is still at an early
      stage of development. The design and synthesis of multifunctionalized and
      multimodal C(60) systems able to cross the cell membranes and efficiently deliver
      active molecules is an attracting challenge that involves multidisciplinary
      strategies. Promising results have emerged in the last years, bringing fullerenes
      again to the front of interest. Herein, the state of the art of this emerging
      field is presented and illustrated with some of the most representative examples.

PMID- 21897968
TI  - Multifunctional nanoadditives for the thermodynamic and kinetic stabilization of
      enzymes.
AB  - Stabilization of enzymes has become a major focus in the quest to improve the
      activity, sustainability and recyclability of enzymes for their successful
      integration into both industry and medicine. Here, we describe the kinetic and
      thermodynamic stabilization of a variety of enzymes in the presence of cationic
      multifunctional polymeric nanoparticles.

PMID- 21897969
TI  - Silent, fluorescent labeling of native neuronal receptors.
AB  - We have developed a minimally-perturbing strategy that enables labeling and
      subcellular visualization of endogenous dendritic receptors on live, wild-type
      neurons. Specifically, calcium-permeable non-NMDA glutamate receptors expressed
      in hippocampal neurons can be targeted with this novel synthetic tri-functional
      molecule. This ligand-directed probe was targeted towards AMPA receptors and
      bears an electrophilic group for covalent bond formation with an amino acid side
      chain on the extracellular side of the ion channel. This molecule was designed in
      such a way that the use-dependent, polyamine-based ligand accumulates the
      chemically-reactive group at the extracellular side of these polyamine-sensitive
      receptors, thereby allowing covalent bond formation between an electrophilic
      moiety on the nanoprobe and a nucleophilic amino acid sidechain on the receptor.
      Bioconjugation of this molecule results in a stable covalent bond between the
      nanoprobe and the target receptor. Subsequent photolysis of a portion of the
      nanoprobe may then be employed to effect ligand release allowing the receptor to
      re-enter the non-liganded state, all the while retaining the fluorescent beacon
      for visualization. This technology allows for rapid fluorescent labeling of
      native polyamine-sensitive receptors and further advances the field of
      fluorescent labeling of native biological molecules.

PMID- 21897970
TI  - Synthesis and antiplasmodial activity of streptocyanine/peroxide and
      streptocyanine/4-aminoquinoline hybrid dyes.
AB  - Two series of streptocyanine dyes incorporating cyclic peroxide or 4
      aminoquinoline moieties are prepared and X-ray diffraction structures for three
      compounds are determined. All hybrid dyes show good antiplasmodial activity (0.06
      to 0.66 MUM) and are not or are slightly cytotoxic, except 10a.

PMID- 21897971
TI  - Magnetic iron oxide nanoparticle enrichment of phosphopeptides on a radiate
      microstructure MALDI chip.
AB  - Several methods can be used to improve the enrichment of phosphorylated proteins.
      In this paper, phosphopeptides were enriched using magnetic iron(II,III) oxide
      (magnetite, Fe(3)O(4)) nanoparticles (NPs) on a radiate microstructure silicon
      chip and then analyzed using matrix-assisted laser desorption/ionization time-of
      flight mass spectrometry (MALDI-TOFMS) without further purification processes. We
      have developed a radiate microstructure chip on which samples can be concentrated
      for analysis by MALDI-TOFMS. The phosphoprotein digests and magnetic iron oxide
      NPs aqueous solution were deposited onto the central zone of the radiate
      microstructure silicon chip and enabled the on-chip enrichment of
      phosphopeptides. Microscopic analysis confirmed that the applied samples were
      confined to the central zone. Sample spots focused on the chip were much smaller
      than those on an unmodified plate with the same total volume. Different additives
      were used and optimized processes were performed to minimize non-phosphopeptides
      interference. These data collectively demonstrate that our on-chip phosphopeptide
      enrichment protocol is a rapid and easy-to-use method for phosphoproteome
      analysis.

PMID- 21897972
TI  - Do all the protic ionic liquids exist as molecular aggregates in the gas phase?
AB  - According to an EI-MS study of 1,1,3,3-tetramethylguanidium-based protic ionic
      liquids (PILs), it has been concluded that not all PILs exist as molecular
      aggregates in the gas phase. The detection of both ions of m/z 115.0 and m/z
      116.0 for the 1,1,3,3-tetramethylguanidinium trifluoromethylsulfonate (TMGS)
      protic ionic liquid indicates that both the molecular and ionic aggregates co
      exist in the gas phase, which is to say that the TMGS may also evaporate via the
      ionic aggregates just like aprotic ionic liquids. Furthermore, investigation on
      triethylamine-based and 1-methylimidazole-based PILs confirmed that the gas phase
      structure of PILs depends on both the acidity and basicity of the corresponding
      acid and base.

PMID- 21897973
TI  - Band gap engineering of bulk ZrO2 by Ti doping.
AB  - It has been experimentally observed that Ti doping of bulk ZrO(2) induces a large
      red-shift of the optical absorption edge of the material from 5.3 to 4.0 eV
      [Livraghi et al., J. Phys. Chem. C, 2010, 114, 18553-18558]. In this work,
      density functional calculations based on the hybrid functional B3LYP show that Ti
      dopants in the substitutional position to Zr in the tetragonal lattice cause the
      formation of an empty Ti 3d band about 0.5 eV below the bottom of the conduction
      band. The optical transition level epsilon(opt)(0/-1) from the topmost valence
      state to the lowest empty Ti impurity state is found at 4.9 eV in a direct band
      gap of 5.7 eV. The calculated shift is consistent with the experimental
      observation. The presence of Ti(3+) species in Ti-doped ZrO(2), probed by means
      of electron paramagnetic resonance (EPR), is rationalized as the result of
      electron transfers from intrinsic defect states, such as oxygen vacancies, to
      substitutional Ti(4+) centers.

PMID- 21897974
TI  - Fungal DNA in hotel rooms in Europe and Asia--associations with latitude,
      precipitation, building data, room characteristics and hotel ranking.
AB  - There is little information on the indoor environment in hotels. Analysis of
      fungal DNA by quantitative PCR (qPCR) is a new method which can detect general
      and specific sequences. Dust was collected through swab sampling of door frames
      in 69 hotel rooms in 20 countries in Europe and Asia (2007-2009). Five sequences
      were detected by qPCR: total fungal DNA, Aspergillus and Penicillium DNA (Asp/Pen
      DNA), Aspergillus versicolor (A. versicolor DNA), Stachybotrys chartarum (S.
      chartarum DNA) and Streptomyces spp. (Streptomyces DNA). Associations were
      analysed by multiple linear regression. Total fungal DNA (GM = 1.08 * 10(8) cell
      equivalents m(-2); GSD = 6.36) and Asp/Pen DNA (GM = 1.79 * 10(7) cell
      equivalents m(-2); GSD = 10.12) were detected in all rooms. A. versicolor DNA, S.
      chartarum DNA and Streptomyces DNA were detected in 84%, 28% and 47% of the
      samples. In total, 20% of the rooms had observed dampness/mould, and 30% had
      odour. Low latitude (range 1.5-64.2 degrees) was a predictor of Asp/Pen DNA.
      Seaside location, lack of mechanical ventilation, and dampness or mould were
      other predictors of total fungal DNA and Asp/Pen DNA. Hotel ranking (Trip
      Advisor) or self-rated quality of the interior of the hotel room was a predictor
      of total fungal DNA, A. versicolor DNA and Streptomyces DNA. Odour was a
      predictor of S. chartarum DNA. In conclusion, fungal DNA in swab samples from
      hotel rooms was related to latitude, seaside location, ventilation, visible
      dampness and indoor mould growth. Hotels in tropical areas may have 10-100 times
      higher levels of common moulds such as Aspergillus and Penicillium species, as
      compared to a temperate climate zone.

PMID- 21897975
TI  - Stereoselective vinylogous Mannich reaction of 2-trimethylsilyloxyfuran with N
      gulosyl nitrones.
AB  - Stereoselective vinylogous Mannich reaction of 2-trimethylsilyloxyfuran with L
      gulose-derived chiral nitrones in the presence of a catalytic amount of
      trimethylsilyl trifluoromethanesulfonate was investigated. The selectivity was
      strongly influenced by the bulkiness of the C-substituent of the nitrone: for
      example, C-benzyloxymethyl nitrone afforded four stereoisomers, whereas bulky C
      [(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]nitrone gave a single stereoisomer. The
      latter product was elaborated to afford key synthetic intermediates for polyoxin
      C and dysiherbaine.

PMID- 21897976
TI  - Dynamics of individual rotational states in an electrostatic guide for neutral
      molecules.
AB  - The guiding properties of individual rotational states of deuterated ammonia
      inside an electrostatic hexapole guide are presented. The guide is combined with
      resonance enhanced multiphoton ionization detection to assess the guiding
      probabilities and velocity distributions as a function of the rotational quantum
      numbers J and K. Due to the differences in the effective dipole moment these
      states are prepared at significantly different translational temperatures. A
      model is presented that describes the velocity-distribution for individual M
      sublevels, and this model is also used to determine a rotational-state dependent
      translational temperature. Furthermore, the hexapole field has been replaced by a
      dipole field in order to obtain a band-pass velocity filter. However, the
      resulting change in the final velocity distribution is similar to that obtained
      from a hexapole guide but with increased backing pressure, leading to collisional
      acceleration of the slow molecules.

PMID- 21897977
TI  - Development of electrochemical based sandwich enzyme linked immunosensor for
      Cryptosporidium parvum detection in drinking water.
AB  - Cryptosporidium parvum is one of the most important biological contaminants in
      drinking water and generates significant risks to public health. Due to low
      infectious dose of C. parvum, remarkably sensitive detection methods are required
      for water and food industry analysis. This present study describes a simple,
      sensitive, enzyme amplified sandwich form of an electrochemical immunosensor
      using dual labeled gold nanoparticles (alkaline phosphatase and anti-oocysts
      monoclonal antibody) in indium tin oxide (ITO) as an electrode to detect C.
      parvum. The biosensor was fabricated by immobilizing the anti-oocysts McAb on a
      gold nanoparticle functionalized ITO electrode, followed by the corresponding
      capture of analytes and dual labeled gold nanoparticle probe to detect the C.
      parvum target. The outcome shows the sensitivity of electrochemical immune sensor
      enhanced by gold nanoparticles with a limit of detection of 3 oocysts/mL in a
      minimal processing period. Our results demonstrated the sensitivity of the new
      approach compared to the customary method and the immunosensors showed acceptable
      precision, reproducibility, stability, and could be readily applied to multi
      analyte determination for environmental monitoring.

PMID- 21897978
TI  - Assessing the spatial resolution of cellular rigidity sensing using a
      micropatterned hydrogel-photoresist composite.
AB  - The biophysical machinery that permits a cell to sense substrate rigidity is
      poorly understood. Rigidity sensing of adherent cells likely involves traction
      forces applied through focal adhesions and measurement of resulting deformation.
      However, it is unclear if this measurement takes place underneath single focal
      adhesions, over local clusters of focal adhesions, or across the length of the
      entire cell. To address this question, we developed a composite, chip-based
      material containing many arrays of 6.5 MUm * 6.5 MUm rigid adhesive islands, with
      an edge-edge distance of 8 MUm, grafted onto the surface of a non-adhesive
      polyacrylamide hydrogel. This material is thus rigid within single islands while
      long-range rigidity is determined by the hydrogel. On soft gels, most NIH 3T3
      cells spread only across two islands in a given dimension forming small stress
      fibers and focal adhesions. On stiff gels, cell spreading, stress fibers, and
      focal adhesions were indistinguishable from those on regular culture surfaces. We
      conclude that rigidity sensing is dictated by material compliance across the cell
      length and that responses to rigidity may be inhibited at any point when large
      substrate strain is encountered during spreading. Our finding may serve as a
      guideline for the design of biomaterials for tissue engineering.

PMID- 21897979
TI  - Microfluidics with aqueous two-phase systems.
AB  - An overview is given about research activities in which aqueous two phase systems
      (ATPSs) are utilized in microfluidic setups. ATPSs consist of two immiscible
      aqueous phases and have traditionally been used for the separation and
      purification of biological material such as proteins or cells. Microfluidic
      implementations of such schemes are usually based on a number of co-flowing
      streams of immiscible phases in a microchannel, thereby replacing the standard
      batch by flow-through processes. Some aspects of the stability of such flow
      patterns and the recovery of the phases at the channel exit are reviewed.
      Furthermore, the diffusive mass transfer and sample partitioning between the
      phases are discussed, and corresponding applications are highlighted. When
      diffusion is superposed by an applied electric field normal to the liquid/liquid
      interface, the transport processes are accelerated, and under specific conditions
      the interface acts as a size-selective filter for molecules. Finally, the
      activities involving droplet microflows of ATPSs are reviewed. By either forming
      ATPS droplets in an organic phase or a droplet of one aqueous phase inside the
      other, a range of applications has been demonstrated, extending from
      separation/purification schemes to the patterning of surfaces covered with cells.

PMID- 21897980
TI  - Monomer adsorption of indocyanine green to gold nanoparticles.
AB  - NIR-dye encoded gold nanoparticles (GNP) are rapidly emerging as contrast agents
      in many bio-imaging/sensing applications. The coding process is usually carried
      out without control or a clear understanding of the metal-liquid interface
      properties which, in contrast, are critical in determining the type and extension
      of dye-metal interaction. In this paper, we investigated the effect of gold
      surface composition on the adsorption of indocyanine green (ICG) on GNP,
      simulating the surface conditions of gold nanorods on citrate-capped gold
      nanospheres. These substrates allowed a careful control of the metal-liquid
      interface composition and, thus, detailed absorption and fluorescence
      concentration studies of the effects of each individual chemical in the colloidal
      solution (i.e. bromide anions, cetyl trimethylammonium ions and Ag(+) ions) on
      the ICG-gold interaction. This study reveals the drastic effect that these
      experimental parameters can have on the ICG adsorption on GNP.

PMID- 21897981
TI  - Incorporation of zinc(II) porphyrins in polyaniline in its perigraniline form
      leading to polymers with the lowest band gap.
AB  - Conjugated copolymers built upon quinone diimine-zinc(II) porphyrin units exhibit
      a very low lying charge transfer band at 800 nm and are strongly emissive from
      the S(2) and T(2) states.

PMID- 21897982
TI  - Reactivity of Lewis pairs (R2PCH2AlMe2)2 with carbon dioxide.
AB  - Species R(2)PCH(2)AlMe(2) (R = Me, Ph) are stable Lewis adducts but still react
      with CO(2) both in solution and in the solid state. The CO(2) adducts undergo a
      rearrangement unprecedented for ambiphilic molecules to form aluminium
      carboxylates. A new spirocyclic compound was also obtained by double Lewis pair
      activation of CO(2).

PMID- 21897983
TI  - Multiple photosynthetic reaction centres using zinc porphyrinic oligopeptide
      fulleropyrrolidine supramolecular complexes.
AB  - Multiple charge-separation sites have successfully been constructed using
      supramolecular complexes of multiporphyrinic oligopeptides [P(ZnP)(n), n = 2, 4,
      8] with fulleropyrrolidine bearing a pyridine or imidazole coordinating ligand,
      which are organized by utilizing pi-pi interaction in addition to the
      coordination bond.

PMID- 21897984
TI  - Plasmid DNA linearization in the antibacterial action of a new fluorescent Ag
      nanoparticle-paracetamol dimer composite.
AB  - Herein, we report the generation of a composite comprised of p-hydroxyacetanilide
      dimer and Ag nanoparticles (NPs) by reaction of AgNO(3) and p-hydroxyacetanilide.
      The formation of the composite was established by UV-vis, FTIR and NMR
      spectroscopy, transmission electron microscopy and X-ray diffraction along with
      substantiation by mass spectrometry. Interestingly, the composite exhibited an
      emission spectrum with a peak at 435 nm when excited by light of wavelength 320
      nm. The composite showed superior antimicrobial activity with respect to its
      individual components against a wide range of Gram positive and Gram negative
      bacteria at relatively low concentrations of Ag NPs and at which there was no
      apparent cytotoxicity against mammalian cells. Our results suggest that the
      composite strongly interacted with the bacterial cell walls leading to cell
      bursting. Interestingly, enhancement in the reactive oxygen species (ROS)
      generation in bacteria was observed in the presence of the composite. It is
      proposed that the ROS generation led to oxidation of the dimer to N-acetyl-p
      benzoquinone imine (NAPQI). The generated NAPQI acted as a DNA gyrase inhibitor
      causing cell death following linearization of DNA.

PMID- 21897985
TI  - Electronic and magnetic properties of pristine and chemically functionalized
      germanene nanoribbons.
AB  - We perform a spin polarized density-functional theory (DFT) study of the
      electronic and magnetic properties of pristine and chemically doped germanene
      nanoribbons (GeNRs) with different widths. It is found that the Ge atom at the
      ribbon edge always prefers to be substituted by an impurity atom. Our study
      reveals that a single N or B atom substitution induces a semiconducting-metal
      transition in armchair oriented germanene nanoribbons (AGeNRs) as evidenced by
      the appearance of a half-filled band with less dispersion; however, N and B co
      doping at the ribbon edges only modifies their band gaps, due to the
      accomplishment of an effective charge compensation. A single N or B atom
      substitution usually turns antiferromagnetic (AFM) semiconducting zigzag
      germanene nanoribbons (ZGeNRs) into ferromagnetic (FM) semiconductors. This AFM
      FM transition is attributed mainly to the perturbation of pi and pi states
      localized at the doped edge. Double atom substitutions (regardless of N-N, B-B or
      N-B configurations) at the edges of ZGeNRs removes the spin-polarization at both
      edges and transforms them into non-magnetic (NM) semiconductors. Moreover, it is
      interesting that some single atom doped ZGeNRs can exhibit a FM half-metallic
      character with 100% spin-polarization at the Fermi level. Our results suggest
      that doped AGeNRs and ZGeNRs have potential applications in Ge-based
      nanoelectronics, such as field effect transistors (FETs), negative differential
      resistance (NDR) and spin filter (SF) devices.

PMID- 21897986
TI  - 6.5% efficient perovskite quantum-dot-sensitized solar cell.
AB  - Highly efficient quantum-dot-sensitized solar cell is fabricated using ca. 2-3 nm
      sized perovskite (CH(3)NH(3))PbI(3) nanocrystal. Spin-coating of the equimolar
      mixture of CH(3)NH(3)I and PbI(2) in gamma-butyrolactone solution (perovskite
      precursor solution) leads to (CH(3)NH(3))PbI(3) quantum dots (QDs) on
      nanocrystalline TiO(2) surface. By electrochemical junction with iodide/iodine
      based redox electrolyte, perovskite QD-sensitized 3.6 MUm-thick TiO(2) film shows
      maximum external quantum efficiency (EQE) of 78.6% at 530 nm and solar-to
      electrical conversion efficiency of 6.54% at AM 1.5G 1 sun intensity (100 mW cm(
      2)), which is by far the highest efficiency among the reported inorganic quantum
      dot sensitizers.

PMID- 21897987
TI  - Peroxide solvation by a toroidal lithium inverse crown ether complex assembled by
      multidentate polyimido sulfonates.
AB  - In this communication we present the synthesis of the inverse crown ether complex
      [Li(2)O(2).Li(4){CH(2)(N(Me)CH(2)S(NtBu)(2))(2)}(2)] (1) which is able to
      accommodate peroxide in a torus of lithium ions.

PMID- 21897988
TI  - Nucleolipid nanovectors as molecular carriers for potential applications in drug
      delivery.
AB  - Novel thymidine- or uridine-based nucleolipids, containing one hydrophilic
      oligo(ethylene glycol) chain and one or two oleic acid residues (called ToThy,
      HoThy and DoHu), have been synthesized with the aim to develop bio-compatible
      nanocarriers for drug delivery and/or produce pro-drugs. Microstructural
      characterization of their aggregates has been determined in pure water and in
      pseudo-physiological conditions through DLS and SANS experiments. In all cases
      stable vesicles, with mean hydrodynamic radii ranging between 120 nm and 250 nm
      have been revealed. Biological validation of the nucleolipidic nanocarriers was
      ensured by evaluation of their toxicological profiles, performed by
      administration of the nanoaggregates to a panel of different cell lines. ToThy
      exhibited a weak cytotoxicity and, at high concentration, some ability to
      interfere with cell viability and/or proliferation. In contrast, DoHu and HoThy
      exhibited no toxicological relevance, behaving similarly to POPC-based liposomes,
      widely used for systemic drug delivery. Taken together, these results show
      nucleolipid-based nanocarriers as finely tunable, multi-functional self
      assembling materials of interest for the in vivo transport of biomolecules or
      drugs.

PMID- 21897989
TI  - Destabilisation of the Li-N-H hydrogen storage system with elemental Si.
AB  - A significant improvement in the dehydrogenation kinetics of the (LiNH(2) + LiH)
      system was obtained upon doping with elemental Si. Whilst, complete
      dehydrogenation of the (LiNH(2) + LiH) system requires more than 2 h, the time
      required for full dehydrogenation was reduced to less than 30 min by doping with
      elemental Si. It is observed that Si thermodynamically destabilises the system
      through the formation of novel intermediate phases resulting from the reaction of
      Si with both LiNH(2) and LiH. Such intermediate phases are also believed to
      enhance reaction kinetics by providing a path for accelerated dehydrogenation and
      the rapid release of hydrogen at the early stages of the reaction. It is believed
      that the dehydrogenation kinetics of the (LiNH(2) + LiH) system, which is
      controlled by the diffusion of H(-) from LiH and H(+) from LiNH(2), becomes
      independent of diffusion upon Si addition due to an enhanced concentration
      gradient in reactive ionic species.

PMID- 21897990
TI  - Stopping paramagnetic supersonic beams: the advantage of a co-moving magnetic
      trap decelerator.
AB  - The long standing goal of chemical physics is finding a convenient method to
      create slow and cold beams intense enough to observe chemical reactions in the
      temperature range of a few Kelvin. We present an extensive numerical analysis of
      our moving magnetic trap decelerator showing that a 3D confinement throughout the
      deceleration process enables deceleration of almost all paramagnetic particles
      within the original supersonic expansion to stopping velocities. We show that the
      phase space region containing the decelerating species is larger by two orders of
      magnitude as compared to other available deceleration methods.

PMID- 21897991
TI  - Characterization of a synthetic peroxodiiron(III) protein model complex by
      nuclear resonance vibrational spectroscopy.
AB  - The vibrational spectrum of an eta(1),eta(1)-1,2-peroxodiiron(III) complex was
      measured by nuclear resonance vibrational spectroscopy and fit using an empirical
      force field analysis. Isotopic (18)O(2) labelling studies revealed a feature
      involving motion of the {Fe(2)(O(2))}(4+) core that was not previously observed
      by resonance Raman spectroscopy.

PMID- 21897992
TI  - Silver catalyzed intramolecular cyclization for synthesis of 3
      alkylideneoxindoles via C-H functionalization.
AB  - A novel protocol for the preparation of various 3-alkylideneoxindoles via a
      silver-catalyzed aromatic C-H functionalization has been developed. The process
      is simple, environmentally conscious, and avoids the use of abundant bases,
      oxidants, or other additives.

PMID- 21897993
TI  - Nickel-catalyzed sp2 C-H bonds arylation of N-aromatic heterocycles with Grignard
      reagents at room temperature.
AB  - A novel protocol for nickel-catalyzed direct sp(2) C-H bond arylation of purines
      has been developed. This new reaction proceeded efficiently at room temperature
      using Grignard reagent as the coupling partner within 5 hours in good to high
      yields. This approach provides a new access to a variety of C8-arylpurines which
      are potentially of great importance in medicinal chemistry.

PMID- 21897994
TI  - The photo-dehydro-Diels-Alder (PDDA) reaction.
AB  - The photo-dehydro-Diels-Alder (PDDA) reaction is a valuable extension of the
      classical Diels-Alder (DA) reaction. The PDDA reaction differs from the DA
      reaction by the replacement of one of the C-C-double bonds of the diene moiety by
      a C-C triple bond and by the photochemical triggering of the reaction. This
      entails that, in contrast to the DA reaction, the PDDA reaction proceeds
      according to a multistage mechanism with biradicals and cycloallenes as
      intermediates. The PDDA reaction provides access to a considerable variety of
      compound classes. For example, 1-phenylnaphthlenes, 1,1'-binaphthyls, N
      heterocyclic biaryls, and naphthalenophanes could be obtained by this reaction.

PMID- 21897995
TI  - An exploratory study of patient attitudes towards symptom reporting in a primary
      care setting. Benefits for medical consultation and syndromic surveillance?
AB  - OBJECTIVES: The aim of this study was to investigate people's attitude towards
      providing symptom information electronically before a consultation. Specific
      areas investigated include a) attitudes and experiences with regards to
      acquisition of information related to symptoms, b) attitudes towards computer
      based communication of symptoms to the general practitioner and how they
      preferred to carry out such reporting, and c) attitudes towards storage, use and
      presentation of symptom-data in general, and particularly in a symptom based
      surveillance setting. METHODS: Data was collected from 83 respondents by use of
      convenience sampling. RESULTS: The respondents were familiar with using the
      Internet for health purposes, such as acquisition of information related to their
      symptoms prior to a consultation. The majority of respondents had a positive
      attitude towards providing information about their symptoms to the general
      practitioner's office as soon as possible after falling ill. Over half of the
      respondents preferred to use e-mail or a web-interface to perform this task.
      Eighty four percent were willing to have their symptom data stored in their EPR
      and 76 percent agreed that the general practitioner might access the symptoms
      together with the prevalence of matching diseases in order to assist the
      diagnostic process during the next consultation. CONCLUSIONS: The results of this
      study support the applicability of electronically mediated pre-consultation
      systems both for improving primary care consultation and for use in symptom based
      surveillance, including real-time surveillance.

PMID- 21897996
TI  - C-Reactive protein and outcomes in acute coronary syndromes: a systematic review
      and meta-analysis.
AB  - Despite the association between high-sensitivity C-reactive protein (CRP) and
      recurrent events in non-ST elevation acute coronary syndromes (ACS), routine
      determination of this marker has not been recommended. In order to verify whether
      the current scientific evidence justifies the inclusion of CRP for risk
      stratification at hospital admission of patients with ACS, we carried out a
      systematic review and meta-analysis of the studies indexed in MEDLINE, SciELO or
      LILACS, with the following inclusion criteria: prospective cohort design and
      assessment of the prognostic value of CPR, as measured using a high-sensitivity
      method at the moment of hospital admission of patients with ACS. Nineteen studies
      met the inclusion criteria. In relation to the long-term follow-up, there was a
      consistent association between CRP and cardiovascular events, with an overall
      odds ratio (OR) of 4.6 (95% CI = 2.3 - 7.6) and overall multivariate OR of 2.5
      (95% CI = 1.8-3.4). As for the short-term, nine studies were positive and six
      were negative, with an overall OR of 1.65 (95% CI = 1.2-2.3). The overall
      multivariate OR was not obtained for the short-term follow-up, because this
      measurement was described only in three heterogeneous studies. Only two short
      term studies analyzed the incremental predictive value of CRP in relation to
      multivariate models, with contradicting results. In conclusion, the small number
      of assessments of the incremental value of CRP, in conjunction with controversial
      results regarding the independent predictive value of CRP for short-term events
      does not support the recommendation of the routine use of CRP for risk
      stratification at admission of patients with ACS.

PMID- 21898007
TI  - A biopsy tool with integrated piezoceramic elements for needle tract
      cauterization and cauterization monitoring.
AB  - This paper reports the feasibility of biopsy needle tract cauterization and
      cauterization monitoring using an embedded array of piezoceramic microheaters.
      Circular heaters of lead zirconate titanate (PZT-5A), with 200 MUm diameter and
      70-80 MUm thickness, are fabricated using a batch mode micro ultrasonic machining
      process. These are then assembled into cavities in the walls of 20-gauge
      stainless steel needles and sealed with epoxy. Experiments are performed by
      inserting the proposed biopsy needle into porcine tissue samples. The needle
      surface exceeds the minimum target temperature rise of 33 degrees C for either
      radial or thickness mode vibrations. The corresponding input power levels are 236
      mW and 325 mW, respectively. The tissue cauterization extends 1-1.25 mm beyond
      the perimeter of the needle and is uniform in all directions. After
      cauterization, the fundamental anti-resonance frequency and the corresponding
      impedance magnitude of the PZT heater decrease by 4.1% and 42.6%, respectively,
      thereby providing a method to monitor the extent of tissue cauterization. A
      sensing interface circuit capable of measuring the resonance frequency shift of
      the PZT elements is built and tested using discrete integrated circuit
      components. The circuit detects the resonance frequency shift from 8.22 MHz to
      7.96 MHz of the PZT elements when the biopsy needle is inserted into wax medium.
      An interface circuit for actuation of the PZT elements for tissue cauterization
      is also described.

PMID- 21898006
TI  - Anal sphincter repair for fecal incontinence: effect on symptom severity, quality
      of life, and anal sphincter squeeze pressures.
AB  - INTRODUCTION AND HYPOTHESIS: The objective of this study was to determine the
      effect of external anal sphincter repair on fecal incontinence symptoms, quality
      of life, and anal sphincter squeeze pressures. METHODS: The fecal incontinence
      symptoms and impact on quality of life, patient satisfaction, and anorectal
      manometry were assessed pre- and post-operatively. RESULTS: One hundred four
      women were eligible and 74/104 (71%) returned post-operative questionnaires.
      Fifty-four of 74 (73%) had pre- and post-operative questionnaires. Twenty-five of
      74 (34%) had pre- and post-operative anorectal manometry measures. Mean length of
      follow-up for participants (n = 54) was 32 +/- 19 months. Modified Manchester
      Health Questionnaire scores decreased from 47.3 +/- 21.9 to 28.4 +/- 24.3 (p <
      0.01) and Fecal Incontinence Severity Index scores from 30.6 +/- 13.0 to 21.6 +/-
      15.5 (p < 0.01). Seventy-seven percent of the participants was satisfied.
      Sphincter squeeze pressures increased from 53.4 +/- 25.0 to 71.8 +/- 29.1 mmHg (p
      < 0.01). CONCLUSIONS: External anal sphincter repair resulted in sustained
      improvements in fecal incontinence severity and quality of life along with
      improved anal sphincter squeeze pressures.

PMID- 21898008
TI  - Electrospray deposition and direct patterning of polylactic acid nanofibrous
      microcapsules for tissue engineering.
AB  - Electrospun nanofibers composed of biodegradable polymers are attractive
      candidates for cell culture scaffolds in tissue engineering. Their fine-meshed
      structures, resembling natural extracellular matrices, effectively interact with
      cell surfaces and promote cell proliferation. The application of electrospinning,
      however, is limited to two-dimensional (2D) or single tube-like scaffolds, and
      the fabrication of arbitrary three-dimensional (3D) scaffolds from electrospun
      nanofibers is still very difficult due to the fibers' continuous and entangled
      form. To address this issue, in this paper, we describe the use of phase
      separation-assisted electrospray and electrostatic focusing to perform continuous
      direct 3D patterning of nanofibrous microcapsules of biodegradable polylactic
      acid (PLA). These microcapsules exhibit fiber-particle duality because they are
      composed of nanofibers suitable for cell attachment while also being easy to
      handle as particles for direct 3D patterning. By varying the flow rate of the
      polymer solution and the humidity of the electrospray atmosphere during
      electrospraying, the diameter of the microcapsule and its surface porosity can be
      controlled. The utility of the direct-patterning process is demonstrated by
      fabricating high-aspect-ratio microscaffolds and subsequent cell cultures. The
      nanofibrous and hollow structure of the microcapsules combined with the direct 3D
      patterning process offers a new approach for fabricating tailor-made scaffolds
      for regenerative medicine.

PMID- 21898009
TI  - Inertial migration of cancer cells in blood flow in microchannels.
AB  - The circulating tumor cell test is used to evaluate the condition of breast
      cancer patients by counting the number of cancer cells in peripheral blood
      samples. Although microfluidic systems to detect or separate cells using the
      inertial migration effect may be applied to this test, the hydrodynamic forces
      acting on cancer cells in high hematocrit blood flow are incompletely understood.
      In the present study, we investigated the inertial migration of cancer cells in
      high hematocrit blood flow in microchannels. The maximum hematocrit used in this
      study was about 40%. By measuring the cell migration probability, we examined the
      effects of cell-cell interactions, cell deformability, and variations in cell
      size on the inertial migration of cancer cells in blood. The results clearly
      illustrate that cancer cells can migrate towards equilibrium positions up to a
      hematocrit level of 10%. We also performed simple scaling analysis to explain the
      differences in migration length between rigid particles and cancer cells as well
      as the effect of hematocrit on cancer cell migration. These results will be
      important for the design of microfluidic devices for separating cells from blood.

PMID- 21898010
TI  - A review of the composition, characteristics, and effectiveness of barrier mesh
      prostheses utilized for laparoscopic ventral hernia repair.
AB  - BACKGROUND: The objective of this review was to provide an overview of the
      components that comprise each of the eight barrier mesh prostheses commonly
      utilized for LVHR and to review the current literature related to the
      characteristics and effectiveness of these materials to guide the general surgeon
      in selecting the most appropriate material for LVHR. METHODS: Composite
      prostheses with permanent barriers (BardTM ComposixTM E/X, BardTM ComposixTM L/P,
      and DUALMESH((r)) Biomaterial) were compared to composite prostheses with
      absorbable barriers (C-QURTM Mesh, PROCEEDTM Surgical Mesh, BardTM SeprameshTM IP
      Composite, ParietexTM Composite, and PHYSIOMESHTM) using scanning electron
      microscopy and a review of the current preclinical and clinical literature.
      RESULTS: Clinical studies and preclinical animal models have attempted to
      determine the adhesion characteristics and effectiveness of barrier mesh
      prostheses available for ventral hernia repair applications. However, it is
      difficult to make any definitive statements about the adhesion characteristics
      and effectiveness of these materials because all meshes were not included in all
      studies and likewise not compared under identical conditions. Overall, ParietexTM
      Composite and DUALMESH((r)) Biomaterial were cited most frequently for
      improvement of adhesion characteristics, followed closely by BardTM SeprameshTM
      IP Composite and C-QURTM Mesh. BardTM ComposixTM, PROCEEDTM Surgical Mesh, and
      uncoated polypropylene were cited most frequently as having the most tenacious
      and extensive adhesions. CONCLUSIONS: Differences observed between the various
      barrier prostheses are likely attributable to the chemical composition of the
      barrier or the conditions required for resorption and metabolism of the barrier
      components. It is likely that the components of these barriers incite a wide
      range of inflammatory responses resulting in the range of adhesion coverage and
      tenacity observed in the preclinical and clinical studies reviewed. Clinical
      trials are needed to more appropriately define the clinical effectiveness of
      these barriers.

PMID- 21898011
TI  - Lobectomy for early-stage lung carcinoma: a cost analysis of full thoracoscopy
      versus posterolateral thoracotomy.
AB  - BACKGROUND: Major pulmonary resections for early-stage non-small-cell lung cancer
      (NSCLC) are increasingly being performed by thoracoscopy, but there are economic
      concerns related to the use of many disposable items and increased operative
      time. We evaluated and compared the costs of thoracoscopic lobectomy versus open
      lobectomy. METHODS: Data from all patients who underwent lobectomy for clinical
      stage I NSCLC from January 1, 2007, to December 31, 2009 were reviewed. Two
      hundred eighty-seven major pulmonary resections (269 lobectomies and 18 anatomic
      segmentectomies) for NSCLC were performed: 98 cases via a totally endoscopic
      approach (TS) and 189 via a classical posterolateral thoracotomy (PLT). Direct
      medical costs [hospital stay, intensive care unit (ICU) stay, disposables,
      theatre time, laboratory, and radiology costs] were evaluated. RESULTS: Patient
      demographics were similar in both groups. The two groups did not differ in
      histology, pathologic stage, or type of lobectomy. There were no differences in
      postoperative complications or readmissions during the 30-day postoperative
      period; however, patients in the TS group had significantly fewer chest tube days
      and shorter hospital length of stay (p < 0.001). Theatre costs were significantly
      higher in the TS group [<euro>2,861 +/- 458 vs. <euro>2,260 +/- 399 (p < 0.001)].
      Mean cost for disposables for TS was <euro>1,800 +/- 560.46 vs. <euro>901 +/- 328
      for PLT (p < 0.001). Thoracoscopic upper-right lobectomy and anatomic
      segmentectomy were more expensive than other thoracoscopic lobectomies. Mean
      costs for hospital stay, laboratory, and radiological services for TS were less
      than for PLT (p < 0.001), although mean ICU stay was similar in both groups.
      Finally, overall costs were significantly greater for the PLT group
      (<euro>14,145.57 +/- 7,117.84) than for the TS group (<euro>11,934.13 +/-
      6,690.25) (p < 0.001). CONCLUSION: Thoracoscopic lobectomy was less expensive
      than open lobectomy for patients with early-stage NSCLC. Although thoracoscopic
      lobectomy has a higher initial cost, overall cost is less expensive due to a
      shorter hospital stay.

PMID- 21898012
TI  - Laparoscopic Nissen versus Toupet fundoplication: objective and subjective
      results of a prospective randomized trial.
AB  - BACKGROUND: Although symptom outcomes following laparoscopic fundoplication have
      been adequately evaluated in the past, comparative subjective data of
      laparoscopic Nissen and Toupet fundoplications are scarce. Multichannel
      intraluminal impedance monitoring (MII) has not been used so far for comparison
      of objective data. METHODS: One hundred patients with documented chronic
      gastroesophageal reflux disease (GERD) were randomly allocated to either floppy
      Nissen fundoplication (group I, n = 50) or Toupet fundoplication (group II, n =
      50). Gastrointestinal Quality of Life Index (GIQLI), symptom grading, esophageal
      manometry, and MII data were documented preoperatively and 3 months after
      surgery. Subjective and objective outcome data were compared to those of healthy
      individuals. RESULTS: Symptom intensity was significantly more severe and GIQLI
      showed impairment in the examined patient population compared to healthy
      controls. Both procedures resulted in a significant improvement in GIQLI and GERD
      symptoms (p < 0.01). Dysphagia improved significantly only in group II, while
      cough, asthma, and distortion of taste improved significantly in both groups.
      Hoarseness symptoms showed some degree of improvement in both groups but reached
      statistical significance only in group I. Postoperatively, bowel symptoms partly
      increased and the ability to belch decreased in both groups (p < 0.05).
      Comparison of postoperative GIQLI and symptom scores showed no significant
      difference between the two groups, except for the ability to belch, which was
      more impaired after Nissen fundoplication. Both procedures resulted in a
      significant improvement in lower esophageal sphincter (LES) pressure; however,
      the improvement was greater in group I than in group II. MII data showed more
      reflux control after Nissen, but the differences between the procedures were not
      significant. CONCLUSIONS: Both procedures equally improve quality of life and
      GERD symptoms. Bowel symptoms may increase after both procedures at the 3-month
      follow-up. Manometry and MII data favor Nissen fundoplication, but dysphagia and
      the inability to belch are more common compared to Toupet fundoplication.

PMID- 21898013
TI  - The role of laparoscopy in the management of acute small-bowel obstruction: a
      review of over 2,000 cases.
AB  - BACKGROUND: Adhesive small-bowel obstruction (SBO) contributes significantly to
      emergency surgical workload. Laparotomy remains the standard approach. Despite
      published reports with high success rates and low morbidity, acute SBO is still
      considered by many a relative contraindication to laparoscopy. Our aim was to
      review the available literature and define important outcomes such as
      feasibility, safety, iatrogenic bowel injury, and benefits to patients with acute
      SBO who are approached laparoscopically. METHODS: A systematic literature search
      was carried out using the Medline database and the search terms "laparoscopy" or
      "laparoscopic approach" and "bowel obstruction." Only adult studies published in
      English between 1990 and 2010 were included. Studies were excluded if data
      specific to outcomes for laparoscopic management of acute SBO could not be
      extracted. RESULTS: Twenty-nine studies were identified. A laparoscopic approach
      was attempted in 2,005 patients with acute SBO. Adhesions were the most common
      etiology (84.9%). Laparoscopy was completed in 1,284 cases (64%), 6.7% were lap
      assisted, and 0.3% were converted to hernia repair. The overall conversion rate
      to midline laparotomy was 29% (580/2,005). Dense adhesions, bowel resection,
      unidentified pathology, and iatrogenic injury accounted for the majority of
      conversions. When the etiology of SBO was a single-band adhesion, the success
      rate was 73.4%. Morbidity was 14.8% (283/1,906) and mortality was 1.5%
      (29/1,951). The enterotomy rate was 6.6% (110/1,673). The majority were
      recognized and converted to laparotomy. Laparoscopy was associated with reduced
      morbidity and length of stay. CONCLUSION: Laparoscopy is a feasible and effective
      treatment for acute SBO with acceptable morbidity. Further studies are required
      to determine its impact on recurrent SBO.

PMID- 21898014
TI  - Effectiveness of combined thoracoscopic-laparoscopic esophagectomy: comparison of
      postoperative complications and midterm oncological outcomes in patients with
      esophageal cancer.
AB  - BACKGROUND: During esophagectomy, laparoscopy can be used together with
      thoracoscopy, but it is not known whether a combined thoracoscopic-laparoscopic
      procedure is associated with fewer postoperative complications than open
      esophagectomy, and without compromising oncological outcome. METHODS: This was a
      longitudinal cohort study that included 185 esophageal cancer patients, including
      72 who underwent combined thoracoscopic-laparoscopic esophagectomy (TLE), 34 who
      underwent thoracoscopic esophagectomy (TE), and 79 who underwent open
      esophagectomy (OE) between January 2002 and May 2010. The main outcome measures
      were postoperative respiratory and overall complications. The secondary outcome
      was 2-year relapse-free survival (RFS). RESULTS: Respiratory complications
      occurred in 9 patients who underwent TLE, 13 who underwent TE, and 31 who
      underwent OE. TLE was associated with fewer respiratory complications (TLE vs.
      OE: odds ratio [OR], 0.22; 95% confidence interval [CI], 0.09-0.53 and TE vs. OE:
      OR, 0.71; 95% CI 0.29-1.76). Overall complications occurred in 34 patients who
      underwent TLE, 20 who underwent TE, and 54 who underwent OE. TLE was associated
      with fewer overall complications (TLE vs. OE: OR, 0.47; 95% CI 0.23-0.94 and TE
      vs. OE: OR, 0.51; 95% CI 0.21-1.25). The 2-year RFS rates were similar among the
      three groups: 71.6% for TLE, 57.7% for TE, and 58.3% for OE (TLE vs. OE: hazard
      ratio, 0.65; 95% CI 0.35-1.20 and TE vs. OE: hazard ratio, 0.91; 95% CI 0.45
      1.82). CONCLUSION: Unlike TE, TLE was associated with fewer postoperative
      complications than was OE, with no compromise of 2-year RFS. A randomized
      controlled trial with longer follow-up is needed.

PMID- 21898016
TI  - Robotic and laparoscopic gastric bypass: are they comparable?

PMID- 21898015
TI  - Inflammatory impact of NOTES peritoneoscopy is not different from that of
      laparoscopy: a randomized comparative study in a survival porcine model.
AB  - BACKGROUND: Inflammatory changes of different NOTES approaches remain unknown.
      The aim of this study was to compare the inflammatory effects of NOTES and
      laparoscopy. METHODS: Forty female pigs were assigned to transgastric,
      transrectal, and transvaginal NOTES and laparoscopic peritoneoscopy groups.
      Antiseptic technique was utilized for NOTES whereas laparoscopy was performed
      sterile. Intraperitoneal pressures were monitored and maintained below 15
      mmH(2)O. Pneumoperitoneum was maintained with CO(2) in all groups. Pre- and
      postoperative blood samples of IL-6, Il-1beta, and TNFalpha, and peritoneal fluid
      collected at surgery were analyzed. Animals were followed daily for 14 days. At
      necropsy, peritoneal fluid was collected for cytokine analysis. RESULTS: Thirty
      nine peritoneoscopies were successfully completed. The median procedure time was
      longer in the NOTES groups (57 min, range = 33-109) than in the laparoscopy group
      (33 min, range 32-36; P < 0.001); this was related to longer incision time and
      closure time. All 39 completed follow-up. Severe bleeding in the post-transrectal
      approach required early sacrifice of the remaining animal. Besides this,
      complications were similar among groups. At necropsy, adhesions were seen in four
      animals in the gastric group, five in the rectal group, two in the vaginal group,
      and two in the laparoscopic group (P = ns). There were no statistical differences
      in serum levels of TNFalpha among the groups. When serum TNFalpha values were
      expressed as the difference from the baseline, in the transvaginal group they
      were significantly lower than in the transrectal at 2 h [0.5 pg/ml (range = -14
      to 59) vs. 60 pg/ml (range = -8 to 303); P = 0.041] and at 8 h [-5.5 pg/ml (range
      = -86 to 55] vs. 37 pg/ml (range = -30 to 62); P = 0.031]. The limitations of
      this study were that the analyses of IL-6 and Il-1beta were not possible because
      most of the samples were below detectable levels, it was an animal model, and the
      sample size was small. CONCLUSION: Inflammatory parameters are similar between
      NOTES and laparoscopic peritoneoscopy despite longer surgery time in the NOTES
      group. The vaginal route seems to reduce the inflammatory stress.

PMID- 21898018
TI  - The simple suture laparoscopic repair of peptic ulcer perforation without an
      omental patch.

PMID- 21898017
TI  - Robot-assisted thymectomy is superior to transsternal thymectomy.
AB  - BACKGROUND: Complete thymectomy is the procedure of choice in the treatment of
      thymomas and in treating selected patients with myasthenia gravis. Transsternal
      thymectomy is the gold standard for most patients. Robot-assisted thymectomy has
      emerged as an alternative to open transsternal surgery. The goal of this study
      was to compare perioperative outcomes in patients who underwent transsternal or
      robot-assisted thymectomy. METHODS: We performed a retrospective review of all
      patients who underwent robot-assisted or transsternal thymectomy at our
      institution from February 2001 to February 2010. Data are presented as mean +/-
      SD. Significance was set as P < 0.05. RESULTS: Fifty patients underwent either
      transsternal (n = 35) or robot-assisted (n = 15) thymectomy. Patient demographics
      and the incidence of myasthenia gravis were similar between groups. There were no
      intraoperative complications or conversions to open surgery in the robot-assisted
      group. Intraoperative blood loss was significantly higher in the transsternal
      group (151.43 vs. 41.67 ml, P = 0.01). There were 20 postoperative complications
      and 1 postoperative death in the transsternal group and 1 postoperative
      complication in the robot-assisted group (P = 0.001). Hospital length of stay was
      4 days (range 2-27 days) in the transsternal group and 1 day (range 1-7 days) in
      the robot-assisted group (P = 0.002). CONCLUSIONS: Robot-assisted thymectomy is
      superior to transsternal thymectomy, reducing intraoperative blood loss,
      postoperative complications, and hospital length of stay. Further investigation
      of the long-term oncologic results in thymoma patients and long-term remission
      rates in patients with myasthenia gravis who underwent robot-assisted thymectomy
      is warranted.

PMID- 21898020
TI  - The endoscopic approach to the neck: a review of the literature and an overview
      of the various techniques.

PMID- 21898019
TI  - Impact of the number of tacks on postoperative pain in laparoscopic repair of
      ventral hernias: do more tacks cause more pain?
AB  - BACKGROUND: The main source of postoperative pain after laparoscopic repair of
      ventral hernia is thought to be fixation of implanted mesh. This study aimed to
      analyze whether a relation exists between the number of tacks used for fixation
      and postoperative pain. METHODS: To reduce the number of prognostic variables,
      only patients with primary umbilical hernia who underwent laparoscopic repair
      with double-crown mesh fixation were enrolled in this study. Two groups differing
      only in the manner of tacking were compared. Group 1 (n = 40), collected from
      previous studies, showed no specific efforts to minimize the number of tacks.
      Group 2 was a cohort of 40 new patients who underwent double-crown fixation using
      the minimal number of tacks considered to provide adequate mesh fixation. To
      eliminate systematic and random errors, the study analyzed only for postoperative
      pain. The severity of the patients' pain was assessed preoperatively and then 2,
      6, and 12 weeks postoperatively using a visual analog scale (VAS) ranging from 0
      to 100. RESULTS: The mean number of tacks used differed significantly between the
      two groups: group 1 (45.4 +/- 9.6) vs group 2 (20.4 +/- 1.4) (p = 0.001).
      Postoperative pain differed significantly only at the 3-month postoperative
      assessment: group 1 VAS (5.78) vs group 2 VAS (1.80) (p = 0.002). CONCLUSIONS:
      Although postoperative pain differed significantly at the 3-month follow-up
      assessment, both VAS scores were so low that from a clinical point of view, this
      difference seems irrelevant. Fewer tacks do not create less pain, nor do more
      tacks create more pain. This absence of a correlation between the number of tacks
      used and postoperative pain may indicate that pain after laparoscopic repair of
      at least small ventral hernias possibly is generated according to some
      "threshold" principle rather than according to a cumulative effect created by
      more points of fixation.

PMID- 21898021
TI  - Risk factors in patient safety: minimally invasive surgery versus conventional
      surgery.
AB  - BACKGROUND: This study aimed to identify the frequency of events in the different
      patient safety risk domains during minimally invasive surgery (MIS) and
      conventional surgery (CS). METHODS: A convenience sample of gynecologic MIS and
      CS was observed. Events were observed and categorized into one of the predefined
      patient safety risk domains. RESULTS: A total of 53 procedures were observed: 26
      CS and 27 MIS procedures. The general characteristics were comparable between the
      two groups. A large number of environmental events were observed, averaging one
      every 2.5 min. Technical events and events of an organizational nature occurred
      more often in MIS (P < 0.01) than in CS (P < 0.01). The relative risk for the
      occurrence of one or more technical events in MIS compared with CS was 1.7, and
      the risk for two or more technical events was 4.1. A time out according to
      protocol showed no relationship to the occurrence of the different types of
      patient safety-related events. CONCLUSION: The technological complexity inherent
      in MIS makes this type of surgery more prone to technology-related problems than
      CS, even in a specially designed minimally invasive surgical suite. A regular
      time-out procedure developed for CS lacks the attention necessary for the complex
      technology used in MIS and therefore is insufficient for MIS procedures briefing.
      Incorporating a specially designed technology checklist in a regular briefing
      protocol could be a solution to decrease the number of events in MIS.

PMID- 21898022
TI  - A single-blind controlled study of electrocautery and ultrasonic scalpel smoke
      plumes in laparoscopic surgery.
AB  - BACKGROUND: Surgical smoke containing potentially carcinogenic and irritant
      chemicals is an inevitable consequence of intraoperative energized dissection.
      Different energized dissection methods have not been compared directly in human
      laparoscopic surgery or against commonly encountered pollutants. This study
      undertook an analysis of carcinogenic and irritant volatile hydrocarbon
      concentrations in electrocautery and ultrasonic scalpel plumes compared with
      cigarette smoke and urban city air control samples. METHODS: Once ethical
      approval was obtained, gas samples were aspirated from the peritoneal cavity
      after human laparoscopic intraabdominal surgery solely using either
      electrocautery or ultrasonic scalpels. All were adsorbed in Tenax tubes and
      concentrations of carcinogenic or irritant volatile hydrocarbons measured by gas
      chromatography. The results were compared with cigarette smoke and urban city air
      control samples. The analyzing laboratory was blinded to sample origin. RESULTS:
      A total of 10 patients consented to intraoperative gas sampling in which only one
      method of energized dissection was used. Six carcinogenic or irritant
      hydrocarbons (benzene, ethylbenzene, styrene, toluene, heptene, and
      methylpropene) were identified in one or more samples. With the exception of
      styrene (P = 0.016), a nonsignificant trend toward lower hydrocarbon
      concentrations was observed with ultrasonic scalpel use. Ultrasonic scalpel
      plumes had significantly lower hydrocarbon concentrations than cigarette smoke,
      with the exception of methylpropene (P = 0.332). No significant difference was
      observed with city air. Electrocautery samples contained significantly lower
      hydrocarbon concentrations than cigarette smoke, with the exception of toluene (P
      = 0.117) and methyl propene (P = 0.914). Except for toluene (P = 0.028), city air
      showed no significant difference. CONCLUSIONS: Both electrocautery and ultrasonic
      dissection are associated with significantly lower concentrations of the most
      commonly detected carcinogenic and irritant hydrocarbons than cigarette smoke. A
      nonsignificant trend toward lower hydrocarbon concentrations was seen with
      ultrasonic scalpel dissection compared with diathermy. The contamination levels
      in city air were largely comparable with those seen after ultrasonic scalpel use.
      Although hydrocarbon concentrations are low, cumulative exposures may increase
      health risks. Where concerns arise, ultrasonic scalpel dissection may be
      preferable.

PMID- 21898023
TI  - Toll-like receptors in the inflammatory response during open and laparoscopic
      colectomy for colorectal cancer.
AB  - BACKGROUND: Surgical interventions activate a cascade of reactions that result in
      an aseptic inflammatory reaction. This inflammatory response initiates the
      organism's innate immunity. Laparoscopic surgery reduces the trauma, and patients
      benefit from diminished surgical trauma and maintained immune function. Cytokine
      levels and C-reactive protein (CRP) are related to the magnitude of surgical
      trauma and surgical stress. Toll-like receptors (TLRs) 2 and 4 are the first
      sensor-recognition receptors of the invading pathogens for the innate immune
      response. This study aimed to compare the inflammatory response and then the
      stress response during laparoscopic and open colectomy for cancer by calculating
      TLR-2 and TLR-4 as the first sensor-recognition receptors together with
      interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and high
      sensitivity CRP (hsCRP). METHODS: A total 40 patients with colorectal cancer were
      randomized in two groups: group A (open colectomy, n = 20) and group B
      (laparoscopic colectomy, n = 20). An epidural catheter was placed in all patients
      1 h preoperatively. Rupivocaine was administered perioperatively and 48 h
      postoperatively. Blood samples were taken for calculation of IL-6, TNF-alpha,
      hsCRP, TLR-2, and TLR-4 preoperatively and 5 min after deflation of
      pneumoperitoneum (group B) or 5 min after division of the colon (group A), then 6
      and 24 h postoperatively. RESULTS: The mean operative time was 115 for group A
      and 142 min for group B. The mean blood loss was respectively 240 and 105 ml (P <
      0.001), and the mean hospital stay was respectively 8 and 5 days (P < 0.05). The
      IL-6 level was significant higher in group A than in group B at 6 and 24 h
      postoperatively (P < 0.0001), and the hsCRP level was significant higher in group
      A than in group B at 24 h postoperatively (P < 0.001). The TNF-alpha values did
      not differ between the two groups. The TLR-2 level was significantly higher in
      group A than in group B at 5 min (P = 0.013) and 24 h (P = 0.007)
      postoperatively. The TLR-4 level was significant higher in group A than in group
      B at 5 min postoperatively (P = 0.03). CONCLUSION: The inflammatory response and
      the resultant stress response are significantly less during laparoscopic
      colectomy than during open colectomy for colorectal cancer. This is an obvious
      short-term clinical benefit for the patient, providing tinder for further study
      to investigate the long-term results of laparoscopic colectomy versus open
      colectomy for colorectal cancer.

PMID- 21898024
TI  - Endoscopic stenting versus operative gastrojejunostomy for malignant gastric
      outlet obstruction.
AB  - BACKGROUND: Malignant gastric outlet obstruction represents a terminal stage in
      pancreatic cancer. Between 5% and 25% of patients with pancreatic cancer
      ultimately experience malignant gastric outlet obstruction. The aim in palliating
      patients with malignant gastric outlet obstruction is to reestablish an oral
      intake by restoring gastrointestinal continuity. This ultimately improves their
      quality of life in the advanced stages of cancer. The main drawback to operative
      bypass is the high incidence of delayed gastric emptying, particularly in this
      group of patients with symptomatic obstruction. This study aimed to compare
      surgical gastrojejunostomy and endoscopic stenting in palliation of malignant
      gastric outlet obstruction, acknowledging the diversity and heterogeneity of
      patients with this presentation. METHODS: This retrospective study investigated
      patients treated for malignant gastric outlet obstruction from December 1998 to
      November 2008 at Nepean Hospital, Sydney, Australia. Endoscopic duodenal stenting
      was performed under fluoroscopic guidance for placement of the stent. The
      operative patients underwent open surgical gastrojejunostomy. The outcomes
      assessed included time to diet, hospital length of stay (LOS), biliary drainage
      procedures, morbidity, and mortality. RESULTS: Of the 45 participants in this
      study, 26 underwent duodenal stenting and 19 had operative bypass. Comparing the
      stenting and operative patients, the median time to fluid intake was respectively
      0 vs. 7 days (P < 0.001), and the time to intake of solids was 2 vs. 9 days (P =
      0.004). The median total LOS was shorter in the stenting group (11 vs. 25 days; P
      < 0.001), as was the median postprocedure LOS (5 vs. 10 days; P = 0.07).
      CONCLUSIONS: Endoscopic stenting is preferable to operative gastrojejunostomy in
      terms of shorter LOS, faster return to fluids and solids, and reduced morbidity
      and in-hospital mortality for patients with a limited life span.

PMID- 21898025
TI  - Transanal endoscopic microsurgery: long-term experience, indication expansion,
      and technical improvements.
AB  - BACKGROUND: This study aimed to review the authors' 16-year experience with
      transanal endoscopic microsurgery (TEM). Mortality, morbidity, recurrence rate,
      and functional outcome were assessed. New indications and technical improvements
      are presented. METHODS: From November 1991 to August 2008, 123 patients (72 men
      and 51 women; median age, 68 years; range, 21-91 years) underwent TEM for
      excision of 105 adenomas with low- or high-grade dysplasia, 9 invasive
      adenocarcinomas (5 curative and 4 palliative resections), 2 neuroendocrine
      tumors, and 2 extramucosal lesions. Five additional patients had excisional
      biopsies, allowing staging after previous endoscopic resection. Most of the
      resections were full-thickness rectal resections using electrocautery or, more
      recently, the Harmonic scalpel. The latest mucosectomies were performed using the
      endoscopic submucosal dissection (ESD) technique. In addition, nontumoral
      indications included pelvic abscess (7 patients) and rectal strictures, which
      were either anastomotic or chemical. Pelvic abscesses were drained transrectally,
      whereas rectal stenoses were treated by strictureplasty. Foreign object retrieval
      and collagen plug placement for anal fistulas were performed using TEM in three
      patients. RESULTS: No mortality occurred. One intraoperative rectal perforation
      required conversion to laparotomy. The postoperative complications included one
      pneumoperitoneum, which was treated medically, and one rectal perforation
      requiring Hartmann's procedure. In the polyp subgroup, six patients (6/91, 7%)
      experienced local recurrence. Pelvic abscesses were successfully treated, and
      stenosis did not recur after strictureplasty. Anorectal manometry showed
      functional alterations without significant clinical impact. CONCLUSIONS: The
      findings showed TEM to be a safe and effective procedure for local excision of
      rectal lesions with a low recurrence rate and minimal consequences in terms of
      anorectal function. In addition, TEM proved to be feasible and effective for
      pelvic abscess drainage and rectal stenosis treatment. New technologies such as
      the Harmonic scalpel and ESD increase the precision already offered by this
      approach.

PMID- 21898026
TI  - Reply to: doi:10.1007/s00464-009-0765-z: Laparoscopic correction of perforated
      peptic ulcer: first choice? A review of literature.

PMID- 21898027
TI  - Flexible CO2 laser and submucosal gel injection for safe endoluminal resection in
      the intestines.
AB  - BACKGROUND: The CO(2) laser's unique wavelength of 10.6 MUm has the advantage of
      being readily absorbed by water but historically limited it to line-of-sight
      procedures. Through recent technological advances, a flexible CO(2) laser fiber
      has been developed and holds promise for endoluminal surgery. We examined whether
      this laser, along with injection of a water-based gel in the submucosal space,
      will allow safe dissection of the intestines and enhance the potential of this
      tool for minimally invasive surgery. METHODS: Using an ex vivo model with porcine
      intestines, spot ablation was performed with the flexible CO(2) laser at
      different power settings until transmural perforation. Additionally, excisions of
      mucosal patches were performed by submucosal dissection with and without
      submucosal injection of a water-based gel. RESULTS: With spot ablation at 5 W,
      none of the specimens was perforated by 5 min, which was the maximum recorded
      time. The time to perforation was significantly shorter with increased laser
      power, and gel pretreatment protected the intestines against spot ablation,
      increasing the time to perforation from 6 to 37 s at 10 W and from 1 to 7 s at 15
      W. During excision of mucosal patches, 56 and 83% of untreated intestines
      perforated at 5 and 10 W, respectively. Gel pretreatment prior to excision
      protected all intestines against perforation. These specimens were verified to be
      intact by inflation with air to over 100 mmHg. Furthermore, excision of the
      mucosal patch was complete in gel-pretreated specimens, whereas 22% of untreated
      specimens had residual islands of mucosa after excision. CONCLUSION: The flexible
      CO(2) laser holds promise as a precise dissection and cutting tool for
      endoluminal surgery of the intestines. Pretreatment with a submucosal injection
      of a water-based gel protects the intestines from perforation during ablation and
      mucosal dissection.

PMID- 21898029
TI  - Darbepoetin alfa (KRN321) is safe and effective when administered subcutaneously
      once every 2 or 4 weeks to patients on peritoneal dialysis in Japan.
AB  - BACKGROUND: Darbepoetin alfa (KRN321) is a recombinant protein that stimulates
      erythropoiesis by the same mechanism as endogenous erythropoietin. Due to its
      longer half-life and greater biological activity than recombinant human
      erythropoietin (rHuEPO), KRN321 maintains an effective hemoglobin (Hb) level at
      extended dose intervals compared with rHuEPO. The efficacy and safety of KRN321
      administered subcutaneously to patients on peritoneal dialysis (PD) were tested.
      METHODS: In a multicenter, open-label, single-arm study, KRN321 was administered
      subcutaneously to patients on PD for 26-28 weeks. Ninety-six patients initially
      were given a 60 MUg subcutaneous dose once every 2 weeks until a target of Hb
      (11.0-13.0 g/dL) was achieved. Thereafter, their dose was every 2 or 4 weeks.
      RESULTS: After the target of Hb was reached in most subjects (96.9%), it was
      maintained with KRN321 administered every 2 or 4 weeks. On completion of (or
      withdrawal from) study, 65 subjects (67.7%) maintained the target Hb. Although a
      number of adverse event related to hypertension occurred, their incidence did not
      appear to be related to Hb or its rate of increase. These events could be
      controlled adequately by interrupting or reducing the dose, and/or treatment with
      antihypertensives. CONCLUSIONS: The efficacy and safety of KRN321 when
      administered subcutaneously for 28 weeks to PD patients were confirmed. It was
      suggested that the quality of life of patients can be improved by treatment with
      KRN321 due to the reduced frequency of administration.

PMID- 21898030
TI  - Proposal for diagnostic criteria for IgG4-related kidney disease.
AB  - BACKGROUND: IgG4-related disease has attracted wide attention recently. It is
      characterized by a high level of serum IgG4 and dense infiltration of IgG4
      positive plasma cells into multiple organs, with the kidney being one
      representative target. Although several sets of diagnostic criteria for
      autoimmune pancreatitis (AIP) are available and renal lesion is recognized as an
      extra-pancreatic manifestation of AIP, it is difficult to differentiate IgG4
      related tubulointerstitial nephritis (TIN) without AIP from other types of TIN.
      To clarify the entity of IgG4-related kidney disease (IgG4-RKD) and support in
      depth studies, the Japanese Society of Nephrology has established a working group
      to prepare diagnostic criteria for IgG4-RKD. METHOD: The working group analyzed
      41 patients with IgG4-RKD, and collected the following data to devise a
      diagnostic algorithm and diagnostic criteria for IgG4-RKD: clinical features
      including extra-renal organ involvement, urinalysis and serological features
      including serum IgG4 levels, imaging findings demonstrated by computed tomography
      (CT), renal histology with IgG4 immunostaining, and response to steroid therapy.
      RESULTS: The conditions for criteria are as follows. (1) Presence of some kidney
      damage, as manifested by abnormal urinalysis or urine marker(s) and/or decreased
      kidney function with either elevated serum IgG level, hypocomplementemia, or
      elevated serum IgE level. (2) Kidney imaging studies showing abnormal renal
      imaging findings, i.e., multiple low density lesions on enhanced CT, diffuse
      kidney enlargement, hypovascular solitary mass in the kidney, and hypertrophic
      lesion of the renal pelvic wall without irregularity of the renal pelvic surface.
      (3) Serum IgG4 level exceeding 135 mg/dl. (4) Renal histology showing two
      abnormal findings: (a) dense lymphoplasmacytic infiltration with infiltrating
      IgG4-positive plasma cells >10/high power field (HPF) and/or ratio of IgG4
      positive plasma cells/IgG positive plasma cells >40%. (b) Characteristic
      'storiform' fibrosis surrounding nests of lymphocytes and/or plasma cells. (5)
      Extra-renal histology showing dense lymphoplasmacytic infiltration with
      infiltrating IgG4-positive plasma cells >10/HPF and/or ratio of IgG4-positive
      plasma cells/IgG-positive plasma cells >40%. The diagnosis is classified into 3
      stages of definite, probable and possible according to the combinations of the
      above conditions. Thirty-nine cases (95.1%) were diagnosed with IgG4-RKD
      according to the criteria. CONCLUSION: The provisional criteria and algorithm
      appear to be useful for clarifying the entity of IgG4-RKD and seeking underlying
      IgG4-RKD cases; however, further experience is needed to confirm the validity of
      these criteria.

PMID- 21898031
TI  - Reversible posterior leukoencephalopathy syndrome after blood transfusion in a
      patient with end-stage renal disease.
AB  - A 42-year-old female end-stage renal disease (ESRD) patient with reversible
      posterior leukoencephalopathy syndrome (RPLS) post-transfusion during initiation
      of hemodialysis is reported. Eleven days after the onset of illness, we diagnosed
      encephalopathy as a grand mal seizure resulting from diffuse cerebral edema. One
      reason for the delayed diagnosis was that her symptom, a throbbing headache that
      occurred during her first dialysis, indicated dialysis disequilibrium syndrome.
      We must bear in mind that a small amount of transfusion could cause RPLS even
      during the first dialysis. To our knowledge, this is the first case report on
      RPLS after blood transfusion in an ESRD patient.

PMID- 21898033
TI  - Brain-derived neurotrophic factor gene polymorphisms, neurotransmitter levels,
      and depressive symptoms in an elderly population.
AB  - A large number of studies have examined associations between brain-derived
      neurotrophic factor (BDNF) gene polymorphisms and depressive symptoms. However,
      results still remain controversial. Recent studies suggested a significant age
      and gender effect on the heritability of depression. The potential
      neurobiological pathways that could possibly mediate this relationship have not
      been examined so far. Since BDNF is involved in the regulation of
      neurotransmitter production, a mediating role of neurotransmitters seems
      plausible. The present study aims to examine the association between three common
      BDNF single-nucleotid polymorphisms (SNPs; rs7103411, rs7124442, and rs6265) and
      depressive symptoms in a community-based elderly population taking into account
      the serum levels of four neurotransmitters, serotonin, dopamine, adrenalin, and
      noradrenalin, as potential mediating factors. We also examined whether age and
      gender had a modifying effect on this association. We collected and analyzed the
      genetic and laboratory data as well as Center for Epidemiologic Studies
      Depression scores of 350 community-dwelling elderly individuals (aged 65+ years).
      We found that the BDNF rs6265 polymorphism was related to the severity of
      depressive symptoms, and that this association was independent of
      neurotransmitter levels. Stratified analyses showed that this association was
      restricted to older individuals (>=74 years) and men. The associations of SNPs
      rs7103411 or rs7124442 SNP with depressive symptoms were not statistically
      significant. This study importantly adds to the existing literature by affirming
      previous assumptions on an age and gender difference in the relation between BDNF
      genotype and depression. We moreover first-time report a missing mediating role
      of neurotransmitters in this association.

PMID- 21898032
TI  - Educational paper: ciliopathies.
AB  - Cilia are antenna-like organelles found on the surface of most cells. They
      transduce molecular signals and facilitate interactions between cells and their
      environment. Ciliary dysfunction has been shown to underlie a broad range of
      overlapping, clinically and genetically heterogeneous phenotypes, collectively
      termed ciliopathies. Literally, all organs can be affected. Frequent cilia
      related manifestations are (poly)cystic kidney disease, retinal degeneration,
      situs inversus, cardiac defects, polydactyly, other skeletal abnormalities, and
      defects of the central and peripheral nervous system, occurring either isolated
      or as part of syndromes. Characterization of ciliopathies and the decisive role
      of primary cilia in signal transduction and cell division provides novel insights
      into tumorigenesis, mental retardation, and other common causes of morbidity and
      mortality, including diabetes mellitus and obesity. New technologies ("Next
      generation sequencing/NGS") have considerably improved genetic research and
      diagnostics by allowing simultaneous investigation of all disease genes at
      reduced costs and lower turn-around times. This is undoubtedly a result of the
      dynamic development in the field of human genetics and deserves increased
      attention in genetic counselling and the management of affected families.

PMID- 21898035
TI  - Influence of menopause on adipose tissue clock gene genotype and its relationship
      with metabolic syndrome in morbidly obese women.
AB  - Menopausal women exhibit a loss of circadian coordination, a process that runs
      parallel with a redistribution of adipose tissue. However, the specific genetic
      mechanisms underlying these alterations have not been studied. Thus, the aim of
      the present study was to determine whether the development of menopause induces
      an alteration of the genes that control biological rhythms in human subcutaneous
      (SAT) and visceral (VAT) adipose tissue, and whether changes in clock gene
      expression are involved in the increased risk of developing metabolic syndrome
      (MetS), which is frequently associated with menopause. To this end, VAT and SAT
      biopsies were taken in pre- (n = 7) and postmenopausal (n = 7) women at similar
      hours in the morning. RNA was extracted, and a microarray analysis was made. Data
      were confirmed by quantitative real-time polymerase chain reaction. Western blot
      and immunohistochemical analysis were also performed. When clock gene expression
      was compared between both groups of women, data in SAT showed that expression of
      the core clock gene period3 was significantly higher in postmenopausal women,
      while casein kinase-1delta, E1A-binding protein and cAMP-responsive element were
      preferentially expressed in the premenopausal group. In VAT, period2 (PER2) and v
      myc myelocytomatosis viral oncogene expressions were significantly higher in the
      postmenopausal group. Western blot analysis indicated that PER2 and PER3 protein
      expression was also increased in postmenopausal women. In addition, several
      genes, including PER2, were differentially expressed depending on whether or not
      the patient met the MetS criteria. We conclude that menopause transition induces
      several changes in the genotype of the adipose tissue chronobiological machinery
      related to an increased risk of developing MetS.

PMID- 21898034
TI  - Effect of aging on islet beta-cell function and its mechanisms in Wistar rats.
AB  - Type 2 diabetes mellitus is characterized by islet beta-cell dysfunction and its
      incidence increases with age. However, the mechanisms underlying the effect of
      aging on islet beta-cell function are not fully understood. We characterized beta
      cell function in 4-month-old (young), 14-month-old (adult), and 24-month-old
      (old) male Wistar rats, and found that islet beta-cell function decreased
      gradually with age. Old rats displayed oral glucose intolerance and exhibited a
      decrease in glucose-stimulated insulin release (GSIR) and palmitic acid
      stimulated insulin release (PSIR). Furthermore, total superoxide dismutase (T
      SOD), CuZn superoxide dismutase (CuZn-SOD), and glutathione peroxidase (GSH-Px)
      activity decreased, whereas serum malondialdehyde (MDA) levels increased in the
      older rats. Moreover, we detected a significant reduction in beta-cell
      proliferation and an increase in the frequency of apoptotic beta-cells in the
      islets of rats in the old group. Finally, Anxa1 expression in the islets of old
      rats was significantly upregulated. These data provide new insights into the
      development of age-related beta-cell dysfunction in rats.

PMID- 21898036
TI  - Role of MRI in the diagnosis and management of patients with clinical scaphoid
      fracture.
AB  - PURPOSE: The American College of Radiologists (ACR) recognises the value of
      magnetic resonance imaging (MRI) as the investigation of choice in patients with
      a clinically suspected scaphoid fracture but normal plain radiographs. The Royal
      College of Radiologists (RCR) in the UK produces no similar guidelines, as
      evidenced by the inconsistent management of such cases in hospitals around the
      UK. In discussion with our musculoskeletal radiologists, we implemented new
      guidelines to standardise management of our patients and now report our findings.
      METHODS: A consecutive series of 137 patients referred to the orthopaedic
      department with clinically suspected scaphoid fracture but normal series of plain
      radiographs were prospectively followed up over a two-year period. We implemented
      the use of early MRI for these patients and determined its incidence of detected
      scaphoid injury in addition to other occult injuries. We then prospectively
      examined results of these findings on patient management. RESULTS: Thirty-seven
      (27%) MRI examinations were normal with no evidence of a bony or soft-tissue
      injury. Soft-tissue injury was diagnosed in 59 patients (43.4%). Of those, 46
      were triangular fibrocartilage complex (TFCC) tears (33.8%) and 18 were
      intercarpal ligament injuries (13.2 %). Bone marrow oedema with no distinct
      fracture was discovered in 55 cases (40.4%). In 17 (12.5%) cases, this involved
      only the scaphoid. In the remainder, it also involved the other carpal bones or
      distal radius. Fracture(s) were diagnosed on 30 examinations (22.0%).
      CONCLUSIONS: MRI should be regarded as the gold standard investigation for
      patients in whom a scaphoid fracture is suspected clinically. It allows the
      diagnosis of occult bony and soft-tissue injuries that can present clinically as
      a scaphoid fracture; it also helps exclude patients with no fracture. We believe
      that there is a need to implement national guidelines for managing occult
      scaphoid fractures.

PMID- 21898037
TI  - Mentoring in complex surgery: minimising the learning curve complications from
      peri-acetabular osteotomy.
AB  - PURPOSE: The aim of this study was to determine whether a complex surgical
      procedure such as peri-acetabular osteotomy could be safely learnt by using a
      programme involving mentoring by a distant expert. To determine this, we examined
      the incidence of intra-operative complications, the acetabulum correction
      achieved, the late incidence of re-operation and progressive degenerative
      arthritis. METHODS: Between 1992 and 2004, peri-acetabular osteotomy was
      performed in 26 hips in 23 patients. The median follow-up was ten (5-17) years.
      The median age of the patients at operation was 28 (14-41) years. Clinical
      outcomes were reported and radiographic results were determined by an independent
      expert. RESULTS: There were no intra-articular osteotomies, sciatic nerve
      injuries, hingeing deformities or vascular injuries. There was one ischial
      nonunion. The lateral centre-edge angle improved from a median 4 degrees  pre
      operatively to 25 degrees . One revision osteotomy, one osteectomy and three
      total hip replacements were required, two for progression of osteoarthritis.
      CONCLUSIONS: The programme of mentoring was successful in that there was a low
      incidence of the major intra-operative complications that are often reported
      during the learning curve period and the acetabular corrections achieved were
      similar to the originators.

PMID- 21898038
TI  - Knee function and prevalence of osteoarthritis after isolated anterior cruciate
      ligament reconstruction using bone-patellar tendon-bone graft: long-term follow
      up.
AB  - PURPOSE: The aim of this investigation was to study patient-reported long-term
      clinical outcome, instrumental stablitity and prevalence of radiological
      osteoarthritis (OA) a minimum of ten years after isolated anterior cruciate
      ligament (ACL) reconstruction. METHODS: An average of 13.5 years after ACL
      reconstruction with bone-patellar tendon-bone (BTB) autograft, 73 patients were
      evaluated. Inclusion criteria consisted of an isolated ACL rupture and
      reconstruction with BPTB graft with no associated intra-articular lesions, in
      particular, cartilage alterations or meniscal lesions. Clinical assessment was
      performed using the International Knee Documentation Committee (IKDC) and Tegner
      and Lysholm scores. Instrumental anterior laxity testing was carried out with the
      KT-1000TM arthrometer. Degree of degenerative changes and prevalence of OA were
      determined using the Kellgren- Lawrence scale. RESULTS: Mean follow-up was 13.5
      years. Mean age was 43.8 years. About 75% of patients were graded A or B
      according to the IKDC score. The Lysholm score was 90.2 +/- 4.8. Radiological
      assessment reported degenerative changes of grade II OA in 54.2% of patients.
      Prevalence of grades III or IV OA was found in 20%. The incidence of OA was
      significantly correlated with stability and function at long-term follow-up.
      CONCLUSION: Arthroscopic ACL reconstruction using BPTB autograft resulted in a
      high degree of patient satisfaction and good clinical results on long-term follow
      up. A higher degree of OA developed in 20% of patients and was significantly
      correlated with increased anterior laxity at long-term follow-up.

PMID- 21898039
TI  - Efficacy and safety of desmopressin for treatment of nocturia: a systematic
      review and meta-analysis of double-blinded trials.
AB  - PURPOSE: The purpose of this analysis was to evaluate the efficacy and safety of
      desmopressin for the treatment of nocturia. METHODS: Databases including MEDLINE,
      EMBASE, ISI web of knowledge, the Cochrane Controlled Trial Register of
      Controlled Trials and Chinese Biological Medical Database were searched to
      identify randomized controlled trials (RCTs) that referred to the efficacy and
      safety of desmopressin for the treatment of nocturia. A systematic review and
      meta-analysis were conducted. RESULTS: Five studies involving 619 participants
      were included for the meta-analysis, and 8 RCTs of cross-over design were also
      identified for the systematic review. The analysis revealed that desmopressin
      might significantly decrease the frequency of nocturnal voids, nocturnal urine
      volume and nocturnal diuresis, potentially resulting in an extended duration of
      the first sleep period and improved sleep quality. The adverse effects of
      desmopressin were similar to those observed in the placebo group. CONCLUSIONS:
      Administered desmopressin was an effective and well-tolerated treatment for
      nocturia.

PMID- 21898040
TI  - Efficacy of pentoxifylline in prevention of contrast-induced nephropathy in
      angioplasty patients.
AB  - BACKGROUND: Contrast-induced nephropathy (CIN) is an adverse consequence of
      contrast media use that results in significant morbidity and mortality and adds
      significant costs to diagnostic and interventional cardiology procedures. Various
      pathophysiological mechanisms have been proposed for CIN and various agents have
      been tested for its prevention. There is currently a general agreement that
      adequate pre-procedure hydration constitutes the cornerstone of prevention, yet
      there are reports of the use of some other agents with various efficacies. We
      prospectively tested pentoxifylline (PTX), an antioxidant, anti-inflammatory
      drug, for CIN prevention in patients undergoing coronary angioplasty. MATERIALS
      AND METHODS: In this prospective, randomized, single-blind, single-center
      clinical trial, 286 consecutive patients were randomly assigned to the control
      group (n = 146), with routine treatment and no PTX, or the study group (n = 140),
      with routine treatment and PTX, 400 mg/tid from 24 h before to 24 h after
      coronary angioplasty. Serum creatinine was measured before and 2 days after the
      procedure. The primary end point was the occurrence of CIN within 48 h. RESULTS:
      The control and PTX groups were comparable in the overall predicted risk of CIN.
      Also, the type and volume of the contrast agent were not significantly different
      between the two groups. Following angioplasty, CIN occurred in 20 (13.69%)
      patients in the control group and in 12 (8.5%) patients in the study group; the
      difference was not statistically significant (P = 0.17). Additionally, there was
      no mortality and need for hemodialysis in either group. CONCLUSION: In
      angioplasty patients, the prophylactic oral use of PTX could be recommended for
      CIN prevention, although no statistically significant protective effect was
      documented.

PMID- 21898041
TI  - Psychometric evaluation of the IWQOL-Lite (Spanish version) when applied to a
      sample of obese patients awaiting bariatric surgery.
AB  - BACKGROUND: Obesity may have an impact on key aspects of health-related quality
      of life (HRQOL). In this context, the Impact of Weight Quality of Life (IWQOL)
      questionnaire was the first scale designed to assess HRQOL. The aim of the
      present study was twofold: to assess HRQOL in a sample of Spanish patients
      awaiting bariatric surgery and to determine the psychometric properties of the
      IWQOL-Lite and its sensitivity to detect differences in HRQOL across groups.
      METHODS: Participants were 109 obese adult patients (BMI >= 35 kg/m(2)) from
      Barcelona, to whom the following measurement instruments were applied: IWQOL
      Lite, Depression Anxiety Stress Scales, Brief Symptom Inventory, and self
      perception items. RESULTS: Descriptive data regarding the IWQOL-Lite scores
      obtained by these patients are reported. Principal components analysis revealed a
      five-factor model accounting for 72.05% of the total variance, with factor
      loadings being adequate for all items. Corrected item-total correlations were
      acceptable for all items. Cronbach's alpha coefficients were excellent both for
      the subscales (0.88-0.93) and the total scale (0.95). The relationship between
      the IWQOL-Lite and other variables supports the construct validity of the scale.
      Finally, sensitivity analysis revealed large effect sizes when comparing scores
      obtained by extreme BMI groups. CONCLUSIONS: This is the first study to report
      the application of the IWQOL-Lite to a sample of Spanish patients awaiting
      bariatric surgery and to confirm that the Spanish version of the instrument has
      adequate psychometric properties.

PMID- 21898042
TI  - Laparoscopic gastric greater curvature plication: results and complications in a
      series of 135 patients.
AB  - Laparoscopic gastric greater curvature plication (LGGCP) is an emerging
      restrictive bariatric procedure that successfully reduces the gastric volume by
      plication of the gastric greater curvature. Its main advantages are the
      reversibility of the technique as well as the lack of foreign materials or
      gastrectomy. We present our results, focusing on the effectiveness and
      complications, and on a new modification of the original technique. One hundred
      and thirty-five patients underwent LGGCP between April 2008 and December 2009. A
      five-trocar port technique was used, and following dissection of the greater
      gastric curvature, single plication of the latter was performed under the
      guidance of a 36-Fr bougie. Modification of the technique included multiple
      gastric plications. One hundred and four obese women and 31 obese men (mean age
      of 36 years) underwent LGGCP for weight reduction. Operative time was 40-50 min,
      and mean hospital stay was 1.9 days (range 1-6 days). After a follow-up of 8-31
      months (mean 22.59), the mean percentage of excess weight loss (%EWL) was 65.29.
      Subgroup analyses based on BMI values showed that %EWL was significantly higher
      for patients with BMI < 45 kg/m2 (group I) compared with patients with BMI > 45
      kg/m2 (group II) (69.86 vs 55.49, respectively, p = 0.006). Similarly, inadequate
      weight loss was significantly higher for group II, while the failure of the
      technique and postoperative complications were comparable. On the other hand,
      subgroup analysis based on the technique showed that the modification of the
      technique did not affect the effectiveness or the operative time; however, it
      reduced early complications dramatically, including prolonged postoperative
      vomiting and late gastric obstruction, thus affecting the length of
      hospitalization. Overall complication rate in our series was 8.8% (12/135). Cases
      of prolonged postoperative vomiting, GI bleeding, and leak were treated
      conservatively, while one case of portomesenteric thrombosis and three cases of
      acute gastric obstruction were treated surgically. LGGCP is an emerging technique
      sparing gastric resection, the use of foreign materials and intestinal bypass.
      Its effectiveness is satisfactory for patients with BMI < 45 kg/m2, and the
      complication rate is acceptable.

PMID- 21898043
TI  - Influence of the metal center and linker on the intracellular distribution and
      biological activity of organometal-peptide conjugates.
AB  - Organometallic complexes conjugated to cell-penetrating peptides (CPPs) are
      promising systems for diagnostic imaging and therapeutic applications in human
      medicine. Recently, we reported on the synthesis of cymantrene(CpMn(CO)(3))-CPP
      conjugates with biological activity on different cancer cell lines. However, the
      precise mechanism of cytotoxicity remained elusive in these studies. To
      investigate the role of the metal center and the linker between the CpM(CO)(3)
      moiety and the peptide, a number of derivatives with manganese replaced by
      rhenium and the keto linker originally used substituted by a methylene group were
      prepared and fully characterized by (1)H NMR spectroscopy, infrared spectroscopy,
      electrospray ionization mass spectrometry, and elemental analysis as well as X
      ray structure determination. The organometal-peptide conjugates as well as
      carboxyfluorescein-labeled derivatives thereof were prepared by solid-phase
      peptide synthesis, purified by high-performance liquid chromatography, and
      analyzed by mass spectrometry. Fluorescence microscopy studies of MCF-7 human
      breast cancer cells revealed an efficient cellular uptake and pronounced nuclear
      localization of the bioconjugates with the methylene linker compared with systems
      with the keto group. In addition, the latter also showed a higher cytotoxicity.
      In contrast, the variation of the metal center from manganese to rhenium had a
      negligible effect. The structure-activity relationships determined in the present
      work will aid in the further tuning of the biological activity of organometal
      peptide conjugates.

PMID- 21898044
TI  - Thermodynamic study of Cu2+ binding to the DAHK and GHK peptides by isothermal
      titration calorimetry (ITC) with the weaker competitor glycine.
AB  - The peptides Asp-Ala-His-Lys (DAHK) and Gly-His-Lys (GHK) are naturally occurring
      Cu(II)-chelating motifs in human serum and cerebrospinal fluid. Here, the
      sensitive thermodynamic technique isothermal titration calorimetry was used to
      study the energetics of Cu(II) binding to DAHK and GHK peptides in the presence
      of the weaker ligand glycine as a competitor. DAHK and GHK bind Cu(II)
      predominantly in a 1:1 stoichiometry with conditional dissociation constants
      [i.e., at pH 7.4, in the absence of the competing chelators glycine and 2-(4-(2
      hydroxyethyl)-1-piperazinyl)ethanesulfonic acid buffer] of 2.6 +/- 0.4 * 10(-14)
      M and 7.0 +/- 1.0 * 10(-14) M, respectively. Furthermore, the apparent DeltaH
      values were measured and the number of protons released upon Cu(II) binding was
      determined by performing experiments in different buffers. This allowed us to
      determine the conditional DeltaG, DeltaH, and DeltaS, i.e., corrected for the
      contributions of the weaker ligand glycine and the buffer at pH 7.4. We found
      that the entropic and enthalpic contributions to the Cu(II) binding to GHK and
      DAHK are distinct, with a enthalpic contribution for GHK. The thermodynamic
      parameters obtained correspond well to those in the literature obtained by other
      techniques, suggesting that the use of the weaker ligand glycine as a competitor
      in isothermal titration calorimetry provides accurate data for Cu(II) binding to
      high-affinity peptides, which cannot be accurately determined without the use of
      a competitor ligand.

PMID- 21898046
TI  - Genetic structure of farmer-managed varieties in clonally-propagated crops.
AB  - The relative role of sexual reproduction and mutation in shaping the diversity of
      clonally propagated crops is largely unknown. We analyzed the genetic diversity
      of yam-a vegetatively-propagated crop-to gain insight into how these two factors
      shape its diversity in relation with farmers' classifications. Using 15
      microsatellite loci, we analyzed 485 samples of 10 different yam varieties. We
      identified 33 different genotypes organized in lineages supported by high
      bootstrap values. We computed the probability that these genotypes appeared by
      sexual reproduction or mutation within and between each lineage. This allowed us
      to interpret each lineage as a product of sexual reproduction that has evolved by
      mutation. Moreover, we clearly noted a similarity between the genetic structure
      and farmers' classifications. Each variety could thus be interpreted as being the
      product of sexual reproduction having evolved by mutation. This highly structured
      diversity of farmer-managed varieties has consequences for the preservation of
      yam diversity.

PMID- 21898045
TI  - Brain-derived neurotrophic factor and Alzheimer's disease: physiopathology and
      beyond.
AB  - Brain-derived neurotrophic factor (BDNF) is the most widely distributed
      neurotrophin in the central nervous system where it plays several pivotal roles
      in synaptic plasticity and neuronal survival. As a consequence, BDNF became a key
      target in the physiopathology of several neurological and psychiatric diseases.
      Recent studies have reported altered levels of BDNF in the circulation, i.e.
      serum or plasma, of patients with Alzheimer's disease (AD), and low BDNF levels
      in the CSF as predictor of future cognitive decline in healthy older subjects.
      Altered BDNF circulating levels have also been reported in other
      neurodegenerative and psychiatric disorders, hampering its use as a specific
      biomarker for AD. Therefore, BDNF seems to be an unspecific biomarker of
      neuropsychiatric disorders marked by neurodegenerative changes.

PMID- 21898047
TI  - Multi-locus species tree of the chub genus Squalius (Leuciscinae: Cyprinidae)
      from western Iberia: new insights into its evolutionary history.
AB  - The phylogenetic relationships of the genus Squalius are believed to be well
      established based on the mitochondrial cytochrome b gene. Here, we inferred the
      phylogenetic relationships of all species inhabiting most of the western Iberia
      river systems using a nuclear multi-locus approach and different species tree
      methods: concatenation and coalescent-based methods (BEST and minimize-deep
      coalescence). The dataset comprised sequences of seven coding and three non
      coding regions belonging to seven nuclear genes, which were chosen to cover
      multiple biological functions: amh, bmp4, ef1a, egr2, irbp, rh and rpl8. We
      provide evidence for a conflicting topology between the nuDNA species tree and
      the widely reported mtDNA gene tree. S. pyrenaicus is rendered paraphyletic in
      all nuDNA species trees, with populations of the Tagus/Colares clustering with S.
      carolitertii, while populations from the Guadiana, Sado and Almargem form a
      separate clade. Although a larger sampling size encompassing the full spectrum of
      Squalius populations in western Iberia is still needed to fully elucidate the
      phylogeography and species delimitation of this genus, our results suggest that
      the two S. pyrenaicus clades may represent different species.

PMID- 21898048
TI  - Healing patterns of choroidal tubercles after antitubercular therapy : A
      photographic and OCT study.
AB  - A 28-year-old female patient with disseminated tuberculosis and choroidal
      tubercles on a regimen of systemic antitubercular therapy underwent fundus
      photography and optical coherence tomography (OCT). This was carried out monthly
      until complete healing of the tubercle was seen. The tubercle consisted of a
      central white-yellow core, consistent with choroiditis, with a faint
      hyperpigmentation surrounding it. There was a surrounding diffuse rim of
      inflammation. By the second month, the hyperpigmented rim was more prominent as
      were the outer edges of both the central core and the outer rim. Over time, the
      outer rim had largely faded with concurrent scar formation in the core. The
      initial OCT analysis revealed a raised RPE-choriocapillaris complex. With
      healing, there was a marked reduction in the choroidal lesional height suggesting
      resolution.

PMID- 21898049
TI  - 1H, 13C, and 15N backbone and side-chain chemical shift assignments for the 31
      kDa human galectin-7 (p53-induced gene 1) homodimer, a pro-apoptotic lectin.
AB  - Galectins are multifunctional proteins with carbohydrate/protein-binding
      properties and distinct expression profiles. Homodimeric galectin-7 (p53-induced
      gene 1) is a potent pro-apoptotic effector with clinical relevance. Here, we
      report (1)H, (13)C, and (15)N chemical shift assignments for human galectin-7
      dimer as determined by using heteronuclear, triple resonance NMR spectroscopy.

PMID- 21898050
TI  - Chemical shift assignments of the catalytic domain from the yeast proline
      isomerase Fpr4p.
AB  - Yeast Fpr4p belongs to the FK506-binding protein (FKBP) class of peptidyl proline
      isomerases (PPIases), and has been implicated in regulating the cis-trans
      conversion of proline residues within histone tails. Here we report the (1)H,
      (13)C and (15)N chemical shift assignments for the bacterially expressed C
      terminal PPIase catalytic domain of Fpr4p. Prediction of secondary structure
      reveals similarity to domains from other members of the FKBP proline isomerases,
      including yeast Fpr1p and the prototypic PPIase region from human FKBP12.

PMID- 21898051
TI  - Dissecting the genetic architecture of agronomic traits in multiple segregating
      populations in rapeseed (Brassica napus L.).
AB  - Detection of QTL in multiple segregating populations is of high interest as it
      includes more alleles than mapping in a single biparental population. In
      addition, such populations are routinely generated in applied plant breeding
      programs and can thus be used to identify QTL which are of direct relevance for a
      marker-assisted improvement of elite germplasm. Multiple-line cross QTL mapping
      and joint linkage association mapping were used for QTL detection. We empirically
      compared these two different biometrical approaches with regard to QTL detection
      for important agronomic traits in nine segregating populations of elite rapeseed
      lines. The plants were intensively phenotyped in multi-location field trials and
      genotyped with 253 SNP markers. Both approaches detected several additive QTL for
      diverse traits, including flowering time, plant height, protein content, oil
      content, glucosinolate content, and grain yield. In addition, we identified one
      epistatic QTL for flowering time. Consequently, both approaches appear suited for
      QTL detection in multiple segregating populations.

PMID- 21898054
TI  - Autography as auto-therapy: psychic pain and the graphic memoir.
AB  - Over the last three decades, the graphic novel has developed both in
      sophistication and cultural importance, now being widely accepted as a unique
      form of literature (Versaci 2007). Autobiography has proved to be a successful
      genre within comics (the word is used in the plural to denote both the medium and
      the philosophy of the graphic form) and within this area a sub-genre, the memoir
      of the artist's own disease or suffering, sometimes known as the graphic
      pathology, has arisen (Green and Myers 2010). Storytelling and healing have been
      linked since ancient times, and the disclosure of ones story forms part of the
      psychotherapeutic treatment of trauma (Herman 1997). This paper will examine, in
      both graphic and textual form, whether, among the myriad reasons that one might
      embark upon the labour intensive work of making a graphic memoir, some artists
      might be seeking some form of healing or catharsis through their work.

PMID- 21898052
TI  - Effect of population size and unbalanced data sets on QTL detection using genome
      wide association mapping in barley breeding germplasm.
AB  - Over the past two decades many quantitative trait loci (QTL) have been detected;
      however, very few have been incorporated into breeding programs. The recent
      development of genome-wide association studies (GWAS) in plants provides the
      opportunity to detect QTL in germplasm collections such as unstructured
      populations from breeding programs. The overall goal of the barley Coordinated
      Agricultural Project was to conduct GWAS with the intent to couple QTL detection
      and breeding. The basic idea is that breeding programs generate a vast amount of
      phenotypic data and combined with cheap genotyping it should be possible to use
      GWAS to detect QTL that would be immediately accessible and used by breeding
      programs. There are several constraints to using breeding program-derived
      phenotype data for conducting GWAS namely: limited population size and unbalanced
      data sets. We chose the highly heritable trait heading date to study these two
      variables. We examined 766 spring barley breeding lines (panel #1) grown in
      balanced trials and a subset of 384 spring barley breeding lines (panel #2) grown
      in balanced and unbalanced trials. In panel #1, we detected three major QTL for
      heading date that have been detected in previous bi-parental mapping studies.
      Simulation studies showed that population sizes greater than 384 individuals are
      required to consistently detect QTL. We also showed that unbalanced data sets
      from panel #2 can be used to detect the three major QTL. However, unbalanced data
      sets resulted in an increase in the false-positive rate. Interestingly, one-step
      analysis performed better than two-step analysis in reducing the false-positive
      rate. The results of this work show that it is possible to use phenotypic data
      from breeding programs to detect QTL, but that careful consideration of
      population size and experimental design are required.

PMID- 21898055
TI  - Evaluation of weekly-reduction regimen of glucocorticoids in combination with
      cyclophosphamide for anti-neutrophil cytoplasmic antibody (ANCA)-associated
      vasculitis in Japanese patients.
AB  - The current therapeutic regimen recommended by the European League against
      Rheumatism (EULAR) for anti-neutrophil cytoplasmic antibody-associated vasculitis
      (AAV) is continuation of initially administered doses of glucocorticoids (GCs) in
      combination with cyclophosphamide (CYC) for 1 month followed by gradual tapering.
      Considering the adverse effects of GCs, another tapering regimen of GCs with CYC,
      which was characterized by tapering GCs weekly, was reported by the British
      Society of Rheumatology (weekly-reduction regimen). The aim of the present study
      is to evaluate the safety and efficacy of this weekly-reduction regimen for
      Japanese AAV patients in comparison with the monthly-reduction regimen
      recommended by the EULAR. We retrospectively reviewed medical records of adult
      patients newly diagnosed with AAV during the period from April 2000 to December
      2010. The outcome measures were rates of remission, relapse, infection, and GC
      induced diabetes mellitus during the first 12 months. Clinical data in the two
      groups and categorial variables with a possible relation to the outcomes were
      compared by using the t test and chi-square test, respectively. Twenty-four
      patients were enrolled in our study. All of the patients achieved remission, and
      the rates of relapse during the first 12 months were not statistically different
      between the two groups (P = 0.16). Patients treated with the weekly-reduction
      regimen were less liable to have infection (P = 0.03) and impaired glucose
      tolerance (P = 0.017), compared with those treated with the monthly-reduction
      regimen. A therapeutic strategy using the weekly-reduction regimen of GCs would
      be effective and would have fewer side effects than the monthly-reduction
      regimen.

PMID- 21898056
TI  - Antinuclear antibody positive autoimmune disorders in North India: an appraisal.
AB  - The autoimmune disorders (AID) have since long been considered to be commoner in
      Western world as compared to Asian countries. This, however, may not be true as
      in developing countries, there are incomplete epidemiological data and lack of
      advanced diagnostic facilities leading to under diagnosis in many cases. In this
      study, we performed an 11-year retrospective analysis of medical records of all
      clinically suspected and immunofluorescence antinuclear antibody test (IF-ANA)
      positive cases. The IF-ANA-positive cases in the year 2006-2007 were further
      analyzed to find out the morbidity contribution by IF-ANA-positive AID. A total
      of 36,310 serum samples were screened for antinuclear antibody (ANA) between the
      years 1996 and 2006. The mean positivity was 12.3%. A constant and statistically
      significant increase in AID was noticed over the last 11 years. In the year 2006
      2007, out of 3,435 suspected AID cases, 18.9% were ANA positive. Of these, 86.0%
      were adult patients with age ranging from 21/4 to 88 years. A female
      preponderance was also noted with a female-to-male ratio of 3:1. Among the ANA
      positive connective tissue disorders (CTD), systemic lupus erythematosus was the
      most common clinical diagnosis (4.6/10,000 cases) followed by scleroderma
      (1.2/10,000) and overlap syndrome (0.7/10,000). Rheumatic, renal and
      hematopoietic systems were commonly involved. The overall frequency of CTD was
      21%. The report is the first and largest hospital-based study from India,
      highlighting the rising incidence and clinical profile of ANA-positive AID.

PMID- 21898058
TI  - Budd-Chiari syndrome as a rare complication of sarcoidosis.

PMID- 21898057
TI  - Cytomegalovirus infection causes morbidity and mortality in patients with
      autoimmune diseases, particularly systemic lupus: in a Chinese population in
      Taiwan.
AB  - To investigate the clinical outcome of cytomegalovirus (CMV) infection in febrile
      hospitalized patients with autoimmune diseases, mostly systemic lupus
      erythematosus (SLE). Fifty-four febrile patients were analyzed retrospectively.
      Half were diagnosed as CMV infection, by positive CMV pp65 antigenemia assay.
      Clinical and laboratory data between two groups were compared. Correlation
      between laboratory data and SELENA-SLEDAI scores/mortality were analyzed in the
      CMV infection group. Receiver operating characteristic analysis was performed to
      determine the cutoff points of different parameters for predicting mortality or
      morbidity. The CMV infection group received a higher corticosteroid dosage (mean
      26.3 mg/day) and a higher percentage of azathioprine use before admission than
      the non-CMV infection group. In the former, the deceased subgroup had a
      significantly higher number of infected leukocytes for CMV (shortened as CMV
      counts, P = 0.013), more cases of bacterial infection (P = 0.090), and a higher
      SLE disease activity index score (P = 0.072) than the alive subgroup. The CMV
      infection group had lower lymphocyte count and more positive bacterial infection
      than the non-CMV infection group did (P = 0.013 and P = 0.027, respectively). A
      level of 25 CMV particles/5 * 10(5) polymorphonuclear neutrophils (PMN) was the
      best cutoff point for predicting CMV-associated mortality, with a sensitivity of
      75.0% and specificity of 72.2%. Moderate dose (30 mg/day) of prednisolone or
      azathioprine use predisposes patients with autoimmune diseases to CMV infection
      with concurrent bacterial infection. In particular, peak CMV counts at 25/5 *
      10(5) PMN or low lymphocyte counts predict mortality or morbidity, respectively.

PMID- 21898059
TI  - Rheumatoid arthritis in patients with hemoglobinopathies.
AB  - Rheumatoid arthritis (RA) in patients suffering from hemoglobinopathies is an
      important clinical problem, but the correlation between these diseases is still
      imperfectly known. The aim of this study was to analyze the clinical, serological
      and radiological characteristics of RA occurring in patients with
      hemoglobinopathies (thalassemia major, thalassemia intermedia and sickle-cell
      disease). In a single institution, in an adult cohort of 90 patients with
      hemoglobinopathies, we investigated retrospectively medical records of the
      patients. We evaluated the clinical findings, the autoantibodies and the
      radiological progression of patients who were diagnosed with RA according the
      American College of Rheumatology (ACR) criteria for RA. There were found 4
      patients, with thalassemia major, who fulfilling the ACR criteria for RA. The
      clinical picture of the patients revealed a mild form of arthritis of the knees,
      shoulders, wrist and hands, while one patient had episcleritis. All patients had
      radiological damage compatible with RA (Larsen's score, 28.75 +/- 29). All had
      positive rheumatoid factor, while anti-cyclic citrullinated peptide antibodies
      were positive in 1 patient. Three patients received steroid treatment and one
      immunosuppressive agent (methotrexate). True RA with low frequency of extra
      articular manifestations is described. The diagnosis of RA must be suspected in
      patients with hemoglobinopathies picture and chronic arthritis of small joints.

PMID- 21898060
TI  - Repeat etanercept administration restores clinical response of patients with
      rheumatoid arthritis.
AB  - We determined whether repeated treatment with the tumor necrosis factor-alpha
      (TNF-alpha) antagonist etanercept can be effective after an initial clinical
      response to this drug is lost. We describe three female patients with active,
      refractory rheumatoid arthritis who were administered with a second course of
      etanercept after eventually becoming refractory to a first course. Disease
      activity was high in all three patients before initial etanercept therapy, and
      each of them had clinically responded by 24 weeks. However, the initial clinical
      effect was lost between 1.5 and 3.5 years thereafter, and tocilizumab was
      administered, but the effect was lost again between 3 and 18 months later. Two
      patients did not respond to subsequent treatment with adalimumab and infliximab.
      Etanercept administered once again reduced disease activity in all three
      patients, none of whom developed any acute side effects. Etanercept re
      administration significantly improved clinical disease activity and inflammatory
      parameters in three patients with RA who were refractory to biological anti-TNF
      agents.

PMID- 21898061
TI  - The association of Raynaud's syndrome with carpal tunnel syndrome: a meta
      analysis.
AB  - Carpal tunnel syndrome (CTS) has traditionally been included among the diseases
      associated with Raynaud's syndrome (RS). The prevalence of RS in patients
      suffering from CTS is not well defined. The objective of this paper was to assess
      the prevalence of RS in patients with CTS-a meta-analysis of published data was
      performed. The PubMed database of the National Library of Medicine and ISI Web of
      Knowledge was used for studies dealing with RS and CTS. The studies provided
      sufficient data to estimate the prevalence of RS in patients of CTS. A forest
      plot was determined by the revealed prevalence. Statistical analysis was based on
      methods for a random effects meta-analysis and a finite mixture model for
      proportions. Publication bias was investigated with the linear regression test
      (Egger's method). A meta-regression was conducted by the year of publication.
      Eight eligible studies, contributing data on 675 subjects, were included in this
      meta-analysis. For CTS, a pooled prevalence of 15.5% and 95% CI (95% CI 0.043,
      0.318) were obtained. Statistically publication bias was present (P value 0.143).
      A mixture model analysis found five latent classes. The meta-regression indicated
      that the estimated prevalence increased when the year of commencement increased,
      too. Within the decade (1957-1967), the odds ratio increased from 1 (95% CI
      1.065, 1.112) to 2.340 (95% CI 1.886, 2.903). Despite some heterogeneity, there
      is a possible indication of an association between RS and patients with CTS.

PMID- 21898062
TI  - Medical costs for Korean patients with rheumatoid arthritis based on the national
      claims database.
AB  - The purposes of this study are to investigate medical resource utilization and
      medical costs of Korean rheumatoid arthritis (RA) patients and to analyze
      predictors in relation to medical costs. National claims data on medical
      treatment were analyzed for the 151,472 RA patients in 2009. For outpatients, the
      mean annual number of visits was 32.5, and the mean annual total outpatient care
      costs were 2.0 million KRW (US$1,594) per patient. On the other hand, the mean
      annual length of stay of inpatients was 22.2 days, and the mean annual total
      inpatient care costs were 3.8 million KRW (US$3,013). Average annual total
      medical costs per patient for all of the RA patients were 2.9 million KRW
      (US$2,310). Total medical costs consisted of 26.1% outpatients' costs, 25.4%
      inpatient, and 48.6% medication costs, making medication costs a predominant cost
      driver. In the multiple regression analysis, biologic use was an important cost
      factor in relation to the annual total medical costs. This study provides
      information on the cost of illness of RA with the population-based representative
      RA patients in Korea, which had not been reported until now.

PMID- 21898063
TI  - Isolated myositis as a sole presentation of familial Mediterranean fever.

PMID- 21898065
TI  - The increasing disease duration of patients at the time of orthopaedic surgery
      for rheumatoid arthritis.

PMID- 21898064
TI  - A case of very late-onset systemic lupus erythematosus and updated pooled
      analysis of late-onset cases in the literature.
AB  - Systemic lupus erythematosus predominantly affects young women during
      childbearing age. It is rare after the age of 90, and there is no report of very
      late onset in persons over 90 in China. Here, we reported a case of a female
      patient, the onset age of whom was 90, analyzing her clinical features and
      treatments. And when conducting a pooled analysis of late-onset cases in the
      literature, we found that the organ damages and severity of lupus disease of old
      onset SLE were not benign, and considering their ages, comorbidities and high
      rate of mortalities, appropriate interventions and close follow-up for this age
      group are needed.

PMID- 21898066
TI  - Effectiveness of microwave diathermy on pain, functional capacity, muscle
      strength, quality of life, and depression in patients with subacromial
      impingement syndrome: a randomized placebo-controlled clinical study.
AB  - The aim of this clinical trial was to evaluate the effectiveness of therapeutic
      MD on pain, functional capacity, muscle strength, quality of life, and depression
      in patients with subacromial impingement syndrome (SIS). A total of 40 inpatient
      subjects with definite SIS were included in this study. These patients were
      sequentially randomized into 2 groups. Group 1 (n = 20) received therapeutic MD.
      Group 2 (n = 20) was served as control group and received sham MD. Superficial
      heat and exercise program were given to both groups. Both of the programs were
      performed 5 times weekly for 3 weeks. Patients were assessed before treatment
      (BT), after treatment (AT), and at a 1-month follow-up (F). Outcome measures
      included visual analogue scale, goniometry, Shoulder Pain and Disability Index,
      Shoulder Disability Questionnaire, shoulder isokinetic muscle testing, handgrip
      strength, Short Form 36, and Beck Depression Index. The patients with SIS in each
      group had significant improvements in pain, shoulder ROM, disability, shoulder
      muscles and grip strength, quality of life, and depression AT and F when compared
      with their initial status (P < 0.05). There was no statistically significant
      difference between the groups according to all the parameters regarding the
      change scores between AT-BT test and F-BT test (P > 0.05). A 2,450-MHz MD regimen
      showed no beneficial effects in patients with SIS, so the superficial heat and
      exercise program, as it is efficient, may be preferable for the treatment of SIS,
      alone.

PMID- 21898068
TI  - Evaluation of the clinical efficacy of Biotene Oral Balance in patients with
      secondary Sjogren's syndrome: a pilot study.
AB  - The objective of the present study was to evaluate the efficacy of Oral Balance
      saliva substitute in alleviating dry mouth symptoms in a sample of patients with
      secondary Sjogren's syndrome. Twenty-one consecutive secondary Sjogren's syndrome
      patients with dry mouth complaints and hyposalivation were included in this
      study. Patients used a lactoperoxidase-system-containing gel (Biotene Oral
      Balance) for 4 weeks. The effects on subjective oral symptoms were recorded by
      means of a 7-items questionnaire which contained questions regarding dry mouth
      sensation and its effect on chewing, swallowing, taste, speech, burning sensation
      and denture retention. The severity of symptoms was assessed using a visual
      analogical scale. Oral symptom scores and unstimulated whole salivary flow were
      recorded at baseline and after 4 weeks' use of the product. Two patients withdrew
      from the study, because of nausea and unpleasant taste caused by the product.
      Nineteen patients (all women, mean age 52.7 years) participated throughout the
      entire study. Wilcoxon signed-ranked tests indicated significant improvements in
      visual analogical scale scores posttreatment for 5 of the 7 items on the oral
      dryness questionnaire, although no increase in salivary flow was found. However,
      the improvement in certain variables did not take a positive course in all cases.
      Patients with lower salivary flow at baseline tended to have greater improvement
      in oral symptoms. The study suggests that the use of Oral Balance gel is
      effective in alleviating the dry mouth symptoms in secondary Sjogren's syndrome
      patients, but a randomized controlled trial is needed to assess the placebo
      effect.

PMID- 21898067
TI  - Gluococorticoid could influence extracellular matrix synthesis through Sox9 via
      p38 MAPK pathway.
AB  - Here, we used glucocorticoid as an apoptosis inducer to study how glucocorticoid
      could accelerate cartilage degeneration and the responsible signal pathway. Human
      chondrocytes were isolated from knee joints gave glucocorticoid of different
      concentrations for 24 h, 48 h, 72 h, or 1 week, and cell viability was
      determined. Next, Sox9, Collagen type II, Aggrecan protein expression and mRNA
      transcription were detected by western blot analysis and quantitative real-time
      PCR, respectively. Glucocorticoid could suppress chondrocyte growth at the
      concentration of 100 MUM. When cultured with glucocorticoid, the expressions of
      Sox9, Col II, and Aggrecan were depressed time-dependent and dose-dependent, as
      well as the mRNA transcription. The glucocorticoid-induced p38 inactivation was
      one mechanism that may response for the inhibition of extracellular matrix
      synthesis, and these influences appeared earlier than the apoptosis effect.

PMID- 21898069
TI  - Clinical features and outcome of microscopic polyangiitis under a new consensus
      algorithm of ANCA-associated vasculitides in Korea.
AB  - The classification system for antineutrophil cytoplasmic antibodies (ANCA)
      associated vasculitis and polyarteritis nodosa had its limitations due to
      numerous overlapping features of these disease entities. The aim of this study is
      to investigate the clinical features and outcome of patients diagnosed with
      microscopic polyangiitis (MPA) according to the newly proposed consensus
      algorithm of ANCA-associated vasculitides and polyarteritis nodosa. Fifty-five
      cases of MPA, comprised of 33 men and 22 women, diagnosed according to a new
      consensus algorithm at a single tertiary hospital were identified for analysis.
      The main clinical features were constitutional symptoms (78.2%), followed by
      renal involvement (74.5%), musculoskeletal symptoms (67.3%), skin manifestations
      (50.9%), neurologic involvement (43.6%), and lung involvement (41.8%). P-ANCA
      and/or anti-myeloperoxidase antibody were present in 69.1%. Five Factor Score and
      Birmingham Vasculitis Activity Score (BVAS) at diagnosis were 1.1 +/- 0.9 and
      10.9 +/- 4.9, respectively. Forty-four patients were available for a long-term
      follow-up, and six patients (13.6%) resulted in death. Mortality was associated
      with BVAS > 9 at the time of diagnosis, age > 60 years, and presence of
      cardiomyopathy and interstitial lung disease. The survival rate at 1 and 3 years
      was 93.9 and 89.2%, respectively. Eight patients (14.5%) required dialysis at the
      time of diagnosis. This is the first study to demonstrate the clinical features
      in patients with MPA using a new consensus algorithm. Survival rate was higher
      than previously reported, and interstitial lung disease was a new risk factor for
      death in patients with MPA.

PMID- 21898070
TI  - Temperature changes in rheumatoid hand treated with nitrogen vapors and cold air.
AB  - The aim of the study was the thermovisual comparison of mean temperature of hand
      surface changes after local cryotherapy with vapors of nitrogen (-160 degrees C)
      and cold air (-30 degrees C). Forty-seven patients with rheumatoid arthritis (39
      women and 8 men; average age 56.2 +/- 10.5 years) were included in the study.
      They had the application of topic cryotherapy using nitrogen vapors or cold air
      on one hand. Main outcome measure was surface temperature of dorsal sides of the
      cooled and contralateral hands. Thermal images of both hands were taken before
      and up to 3 h after the treatment. One minute after application, nitrogen vapors
      induced decrease in surface skin temperature of the cooled hand from 28.9 +/- 1.8
      degrees C to 17.9 +/- 2.2 degrees C, P < 0.05, whereas cold air from 29.4 +/- 2.4
      degrees C to 23.1 +/- 2.2 degrees C, P < 0.05. However, significantly lower
      temperature was obtained with vapors of nitrogen (P < 0.05). Just after the
      treatment, a rapid rewarming occurred and hands reached baseline temperature in
      15 min in both applications and they did not differ till the end of the
      procedure. Both nitrogen vapors and cold air induce similar temperature changes
      in hands with the exclusion of temperature obtained 1 min after the treatment.
      Changes in non-cooled hands indicate contralateral reaction.

PMID- 21898071
TI  - Dysregulated expression of dicer and drosha in breast cancer.
AB  - Large-scale profiling approaches have revealed global down-regulation of
      microRNAs (miRNAs) in several human cancer types including breast cancer. Altered
      expression of Dicer and Drosha, two key enzymes in the miRNA maturation, is
      believed to be one of the most important mechanisms. By using quantitative real
      time RT-PCR (QT-PCR), we examined the expression of Dicer and Drosha in 49 pairs
      of matched human breast cancer tissues. Decreased expression was observed in
      53.1% (Dicer), 51.9% (Drosha) and 75.5% (Dicer plus Drosha) breast cancer
      tissues. In conclusion, the decreased expression of Dicer and Drosha may play a
      role in down-regulation of miRNAs in breast cancer.

PMID- 21898072
TI  - Germ cells of male mice express genes for peroxisomal metabolic pathways
      implicated in the regulation of spermatogenesis and the protection against
      oxidative stress.
AB  - Peroxisomes are organelles with main functions in the metabolism of lipids and of
      reactive oxygen species. Within the testis, they have different functional
      profiles depending on the cell types. A dysfunction of peroxisomes interferes
      with regular spermatogenesis and can lead to infertility due to spermatogenic
      arrest. However, so far only very little is known about the functions of
      peroxisomes in germ cells. We have therefore analyzed the peroxisomal compartment
      in germ cells and its alterations during spermatogenesis by fluorescence and
      electron microscopy as well as by expression profiling of peroxisome-related
      genes in purified cell populations isolated from mouse testis. We could show that
      peroxisomes are present in all germ cells of the germinal epithelium. During late
      spermiogenesis, the peroxisomes form large clusters that are segregated from the
      spermatozoa into the residual bodies upon release from the germinal epithelium.
      Germ cells express genes for proteins involved in numerous metabolic pathways of
      peroxisomes. Based on the expression profile, we conclude that newly identified
      functions of germ cell peroxisomes are the synthesis of plasmalogens as well as
      the metabolism of retinoids, polyunsaturated fatty acids and polyamines. Thus,
      germ cell peroxisomes are involved in the regulation of the homeostasis of
      signaling molecules regulating spermatogenesis and they contribute to the
      protection of germ cells against oxidative stress.

PMID- 21898073
TI  - Link to slower access to care: what is the stigma?: an Indian perspective.
AB  - Stigma and discrimination have been "bed fellows" of HIV and AIDS in India.
      Perpetuated by lack of awareness, deep-rooted traditional beliefs, adherence to
      harmful practices, and a moralistic tag associated with a condition connected
      with sex (in India the method of HIV transmission being largely heterosexual in
      nature) and high-risk individuals such as sex workers, it made it difficult for
      the country to fight an epidemic that was hard to track, estimate, diagnose, and
      treat. Various interventions under India's National AIDS Control Program (NACP)
      have targeted stigma and discrimination among different groups. The program has
      been fairly successful in its outreach programs, bringing about a reduction in
      adult HIV prevalence and new infections. As the country transitions from NACP
      Phase III (2007-2012) to IV (2012-2017), making treatment and longevity its top
      priority, stigma is no longer such a terrifying word. This review discusses the
      social and cultural context of HIV/AIDS-related stigma in general and highlights
      various policies and intervention programs that have led India's campaign against
      HIV/AIDS-driven stigma into the testing, care, support, and treatment ambit.

PMID- 21898074
TI  - Effectiveness and safety of adalimumab in Japanese patients with rheumatoid
      arthritis: retrospective analyses of data collected during the first year of
      adalimumab treatment in routine clinical practice (HARMONY study).
AB  - We retrospectively investigated the ability of adalimumab (ADA) to reduce disease
      activity, improve physical function, and retard the progression of structural
      damage in 167 patients with rheumatoid arthritis. Clinical and functional
      outcomes were compared between patients with or without prior biologic treatment
      and those with or without concomitant methotrexate (MTX) treatment. At week 52,
      38.3% achieved clinical remission: 42.4 and 28.6% of patients achieved remission
      in those without and with previous biologics, respectively, while 42.7 and 12.5%
      of patients achieved remission in those with and without concomitant MTX,
      respectively. ADA treatment significantly reduced the rate of radiographic
      progression from 27.1 +/- 46.0 (median 13.6; 25th-75th percentiles 8.3 to 28.9)
      at baseline to 0.8 +/- 5.0 (median 0.0; 25th-75th percentiles -0.9 to 2.0) at
      week 52 (P < 0.0001). Radiographic progression was absent in 59.8% of patients.
      Sixty adverse events (34.21/100 patient-years) were reported, 16 of which were
      serious (9.12/100 patient-years). ADA therapy is highly effective for reducing
      disease activity, improving physical function, and limiting radiographic
      progression. It is generally safe and well tolerated by Japanese RA patients in
      routine clinical practice.

PMID- 21898075
TI  - Delayed treatment with tumor necrosis factor inhibitors in incomplete responders
      to synthetic disease-modifying anti-rheumatic drugs shows an excellent effect in
      patients with very early rheumatoid arthritis with poor prognosis factors.
AB  - We aimed to investigate whether delayed treatment with tumor necrosis factor
      (TNF) inhibitors in incomplete responders to synthetic disease-modifying anti
      rheumatic drugs (DMARDs) was effective among patients with very early rheumatoid
      arthritis (RA) with poor prognosis factors. We examined 22 patients with very
      early RA who were positive for anti-cyclic citrullinated peptide antibodies or
      IgM-rheumatoid factor. The mean disease duration at entry was 14.1 weeks. A treat
      to-target strategy, aiming at simplified disease activity index (SDAI) remission,
      was initiated with synthetic DMARDs. SDAI remission was not achieved in 9 of the
      22 patients with synthetic DMARDs alone, and TNF inhibitors were added in these
      patients. SDAI values in these 9 patients were further examined for the following
      6 months. The TNF inhibitors (infliximab 8, etanercept 1) were added at a mean
      interval of 34.1 weeks after the initiation of synthetic DMARDs. SDAI remission
      was achieved in 4 of the 9 patients (44.4%) at 3 months and in 8 of the 9
      patients (88.9%) at 6 months after the introduction of the TNF inhibitors.
      Radiographic damage had not progressed in these patients. Delayed treatment with
      TNF inhibitors is effective and tolerable for patients with very early RA with
      poor prognosis factors.

PMID- 21898076
TI  - Genotoxicity potential of a new natural formicide.
AB  - BACKGROUND, AIM, AND SCOPE: Assessment of environmental impacts from pesticide
      utilization should include genotoxicity studies, where the possible effects of
      mutagenic/genotoxic substances on individuals are assessed. In this study, the
      genotoxicity profile of the new formicide Macex(r) was evaluated with two
      genotoxicity tests, namely, the micronucleus test with mouse bone marrow and
      Vicia faba, and a mutagenicity test using the Ames Salmonella assay. MATERIALS
      AND METHODS: The bacterial reverse mutation test (Salmonella typhimurium strains
      TA97, TA98, TA100, TA102, and TA1535), the Vicia root tip and mouse micronucleus
      tests were conducted according to published protocols. RESULTS: In the range of
      the formicide Macex(r) concentrations tested from 0.06 to 1.0 g L-1 (or mgkg-1 in
      the mouse test), no genotoxicity was observed in the prokaryotic or eukaryotic
      test organisms. However, at Macex(r) concentrations of 0.5 g L-1 and above a
      significant decrease in the mitotic index (P <= 0.05) in the V. faba was
      observed. Micronucleus formation was likewise increased in the test organism at
      concentrations starting at 2.0 g L-1. CONCLUSIONS: These data allow us to
      classify this natural formicide preparation as a product with no geno
      environmental-impact when applied at recommended concentrations.

PMID- 21898077
TI  - Effect of aging biosolids with soils of contrasting pH on subsequent
      concentrations of Cu and Zn in pore water and on their plant uptake.
AB  - PURPOSE: The study examines if a short period of reaction after addition of
      biosolids to soils can reduce the solubility and potential phytotoxicity of
      biosolid-borne Zn and Cu. METHODS: The effects of period of aging (zero, 60, and
      120 days) of biosolids (applied at 0, 10, 20, and 30 g kg-1) with an acid,
      neutral, or alkaline soil on pH and concentrations of Zn, Cu, and dissolved
      organic C in solution over a 60-day growth period of spinach were investigated
      using Rhizon pore water samplers. RESULTS: In the acid and neutral soils,
      increasing aging period markedly reduced the concentrations of Zn and Cu in
      solution and there were concomitant increases in solution pH. The effect was much
      less pronounced in the alkaline soil. Soluble Zn and Cu concentrations were
      generally positively correlated with dissolved organic C concentrations,
      negatively correlated with pH in the alkaline and neutral soils but positively
      correlated with pH in the acid soil. Spinach yields were lower in the acid than
      neutral and alkaline soils and tended to increase with increasing rates of
      biosolids in all three soils. The concentrations of tissue Zn and Cu were notably
      high in shoots of plants grown in the acid soil. For all biosolid-amended soils,
      the concentrations of tissue Cu were lower in plants grown after 60 days rather
      than no aging. CONCLUSIONS: Following biosolids applications to soils, an aging
      period of only a few months is likely to lower the solubility, and potential
      phytotoxicity, of biosolid-borne Zn and Cu particularly in acid and neutral
      soils.

PMID- 21898078
TI  - Predicting factors for emergency peripartum hysterectomy in women with placenta
      previa.
AB  - PURPOSE: The aim of the study was to identify predictive factors for peripartum
      hysterectomy in women with placenta previa. METHODS: We retrospectively reviewed
      all singleton pregnancies with a diagnosis of placenta previa, with the distance
      between the lower placenta edge and the internal cervical os is <=2 cm, during
      the period June 2006-May 2010. Antepartum characteristics of women who did and
      did not undergo peripartum hysterectomy were compared: they include demographical
      data, obstetrics history, clinical course of the index pregnancy and sonographic
      findings. RESULTS: Two-hundred and forty-seven women were selected. peripartum
      hysterectomy was required in 12 cases (4.9%). A statistically significant
      increased risk emerged for a history of cesarean section (p < 0.001), major
      placenta previa (p < 0.001), sonographic suspect of placenta accreta (p < 0.001)
      and gestational age at delivery <34 weeks' gestation (p < 0.001). These four
      variables were entered into an unconditioned logistic regression model. The
      resulting adjusted ORs were 23.1 (95% CI 2.3-235.3, p = 0.008), 14.6 (95% CI 0.6
      346.5, p = 0.097), 42.4 (95% CI 5.1-354.5, p = 0.001) and 9.3 (95% CI 1.1-76.9, p
      = 0.037), respectively. CONCLUSIONS: This study confirms that placenta previa is
      a condition at substantial risk of peripartum hysterectomy. A history of cesarean
      section, the sonographic suspect of placenta accreta and gestational age at
      delivery were found to be independently associated with this risk. Antepartum
      ultrasonography in particular plays a crucial role in predicting hysterectomy in
      these cases.

PMID- 21898079
TI  - Application of 1.5 T magnetic resonance imaging in endometrial cancer.
AB  - OBJECTIVE: To determine the diagnostic accuracy, sensitivity and specificity of
      magnetic resonance imaging (MRI) in detecting myometrial invasion, cervical
      involvement and disease stage in endometrial cancer. METHODS: 168 consecutive
      patients with endometrial carcinoma underwent preoperative MRI. We classified
      myometrial invasion as no invasion, <=50% invasion or >50% invasion and cervical
      involvement as positive or negative. The preoperative MRI findings and stagings
      were compared with final surgical and histological staging; the latter was taken
      as the gold standard. Standard statistical calculations were used. RESULTS: The
      sensitivity, specificity, and accuracy of MRI for the detection of myometrial
      invasion >50% were 64.7, 92.5, and 86.9%, respectively. Positive and negative
      predictive values were 68.8 and 91.2%, respectively. The sensitivity,
      specificity, and accuracy of MRI for the detection of cervical invasion were
      52.63, 93.08, and 83.93%, respectively. Positive and negative predictive values
      were 68.97 and 87.05%, respectively. 102 cases were classified as stage IA (early
      disease) by histology. MRI accurately predicted the degree of invasion in 88
      cases and overestimated in 14, giving a sensitivity of 86.3% and specificity of
      69.1%. However, MRI showed reduced sensitivity for predicting stage IB and
      advanced endometrial cancer (stages III and IV) at 33.3 and 30.3%, respectively,
      but was found to be specific for predicting these stages; the specificity were
      94.7 and 85.1%, respectively. MRI also showed good accuracy for predicting stage
      IA, IB, II and advanced endometrial cancer at 80.4, 86.9, 91.7, and 83.9,
      respectively. CONCLUSION: MRI assists in planning the surgical treatment of
      endometrial cancer with good accuracy and specificity, although sensitivity is
      suboptimal.

PMID- 21898080
TI  - Lymphocyte subpopulations in Chinese women with Turner syndrome.
AB  - PURPOSE: Turner syndrome (TS) is associated with deficiency of cellular and
      humoral immunity. However, the characteristics of lymphocyte subpopulations in
      Chinese women with TS have not been reported. In this study, the percentage of
      lymphocyte subpopulations and the mRNA expression of some transcription factors
      were determined in patients with TS. The effect of the hormone substitution on
      lymphocyte subpopulations was also analyzed. METHODS: Thirteen Chinese TS women
      and eight age and sex-matched healthy volunteers were studied. The percentage and
      mean fluorescence intensity (MFI) of lymphocyte subpopulations including
      CD3+CD4+, CD3+CD8+, CD19-CD138+, CD4+CD25+FoxP3+ and CD4+CD8-IL17A+ cells were
      determined by flow cytometry. The mRNA expression of some transcription factors
      were detected by RT-PCR. RESULTS: Compared to control, the percentage of CD3+CD4+
      cells was significantly reduced (p < 0.05), while the percentage of CD19-CD138+,
      CD4+CD25+FoxP3+ and CD4+CD8-IL17A+ cells was significantly increased in TS
      patients. No difference was observed in the percentage of CD3+CD8+, CD19+ B cells
      between TS patients and healthy volunteers, with the similar changes in the mean
      fluorescence intensity of these cells. The mRNA expression of some transcription
      factors slightly enhanced in TS patients. Estrogen therapy did not affect the
      percentage of lymphocyte subpopulations. CONCLUSION: These findings suggested
      that Turner syndrome might be associated with changes of lymphocyte
      subpopulations.

PMID- 21898081
TI  - What is the impact of cervical invasion on lymph node metastasis in patients with
      stage IIIC endometrial cancer?
AB  - PURPOSE: The aim of this study was to evaluate whether the presence of cervical
      invasion has altered the site of lymph node (LN) metastasis in stage IIIC
      endometrial cancer (EC) patients. METHODS: Fourty-six patients who had systematic
      pelvic and para-aortic lymphadenectomy surgery for EC and staged as IIIC were
      included in the study. Patients with cervical invasion were defined as Group A
      and patients without cervical invasion were defined as Group B. The groups were
      compared according to surgical-pathologic characteristics. Chi-square and Annova
      table test were used to examine the effect of cervical invasion on LN metastasis.
      RESULTS: The mean age of patients was 59 years (range 38-81) and tumor size was
      47 mm (range 10-80). Twenty-three patients had cervical involvement (Group A) and
      23 had no cervical metastasis (Group B). Groups were not different with regard to
      cell type, grade, depth of myometrial invasion, tumor size, adnexal involvement,
      peritoneal metastasis and lymphovascular space invasion. Among 46 patients
      obturator LN was the most involved site of LN metastasis, however, when there is
      cervical metastasis external iliac LN was found to be the most involved LN site.
      Patients without cervical invasion had 21.7% of external iliac LN metastasis
      while patients with cervical invasion had 60.9% of external iliac LN metastasis.
      Also, cervical invasion has increased the risk of pelvic LN and obturator LN
      involvement from 82.6 to 95.7% and 39.1 to 52.2%, respectively. CONCLUSION:
      Cervical invasion may have an effect on lymphatic spread and change the site of
      metastatic LNs. Large prospective studies are needed to clarify the alteration of
      LN metastasis in cervix invaded EC patients.

PMID- 21898082
TI  - Calcified metastases from ovarian carcinoma highlighted by F-18 FDG PET/CT:
      report of two cases.
AB  - Two cases of postoperative female patients with ovarian serous papillary
      carcinoma were referred for F-18 Fluorodeoxyglucose (F-18 FDG) PET/CT to evaluate
      suspicious recurrence and/or metastasis. One patient presented with multiple
      extensive calcified lesions with increased FDG uptake in the abdominopelvic
      cavity and the series of PET/CT scans showed progression of disease after
      chemotherapy. The other patient presented with three calcified masses with
      intensive uptake of FDG located in the left pelvis, the right subphrenic region,
      and the right supradiaphragmatic area, respectively. These suggest that F-18 FDG
      PET/CT can be useful in identifying malignant calcification and assessing
      therapeutic response of calcified malignancy.

PMID- 21898083
TI  - Epidemiology, treatment and prevention of healthcare-associated urinary tract
      infections.
AB  - OBJECTIVES: Healthcare-associated urinary tract infections (HAUTIs) are the most
      frequent healthcare-associated infections in general hospitals. They are almost
      exclusively complicated UTIs, although complicating factors are very
      heterogenous. HAUTIs are mainly catheter associated. Most of them are
      asymptomatic and do not need antimicrobial therapy. However, cross-contamination
      and cross-infection may contribute to distribution of resistant uropathogens. The
      bacterial spectrum of HAUTI is broad, and antibiotic resistance is common.
      METHODS: The authors reviewed the literature from 2000 to 2010 to determine the
      epidemiology, prevention and best treatment strategies for HAUTI. The
      recommendations were summarized by determining the level of evidence and grading
      each recommendation. RESULTS: The treatment for HAUTI encompasses treatment for
      complicating factors as well as antimicrobial chemotherapy. At least in serious
      UTI, adequate initial antibiotic therapy results in lower mortality. Therefore,
      the initial antibiotic regimen must provide sufficient antibiotic coverage. This
      can only be achieved if the local or regional bacterial spectrum and antibiotic
      resistance patterns of uropathogens are followed continuously. Provisional
      microbiological findings, such as reports on Gram-stain or certain biochemical
      results, can lead to early stratification of pathogens and allow a more tailored
      empiric antibiotic therapy. Antibiotic therapy of HAUTI has to consider
      therapeutic success in the individual patient and prevention of emergence of
      antibiotic-resistant mutants. For both aspects, adequate drug selection and
      dosing are paramount. DISCUSSION: Antibiotic treatment for HAUTI should follow
      prudent antibiotic use to prevent emergence of antibiotic resistance.

PMID- 21898084
TI  - Clinical characteristics, nocturnal antidiuretic hormone levels, and
      responsiveness to DDAVP of school children with primary nocturnal enuresis.
AB  - PURPOSE: Decreased nocturnal antidiuretic hormone (ADH) excretion has been
      suggested to be a causative factor for PNE in children. We investigate the
      demographic characteristics and nocturnal ADH levels of children with PNE who
      attended a tertiary referral center and to determine their response to treatment
      with desamino-D-arginine vasopressin (DDAVP). METHODS: We performed a
      retrospective study in 90 PNE children aged 6-12 years. We recorded the gender,
      height, weight, number of children per family, and psychosocial problems and
      compared these findings with the corresponding data obtained from a national
      survey. We also measured the nocturnal ADH levels and evaluated the response rate
      to DDAVP. RESULTS: The number of PNE patients decreased with an increase in age.
      Enuresis was significantly associated with male gender (P = 0.044) and more
      number of children per family (P = 0.043). The rates of comorbidity with
      defecation problems, obesity, attention-deficit hyperactivity disorder (ADHD),
      and overweight were 36.7, 17.8, 12.2, and 10%, respectively. Although the
      prevalence of obesity and ADHD was higher among children with PNE, there was no
      significant difference between PNE patients and their prevalence in the
      community. The ADH levels at 2 a.m. and 8 a.m. were 0.87 +/- 0.75 and 0.89 +/-
      0.76 pg/ml, respectively. In the 50 (55.5%) patients who received DDAVP
      treatment, the complete- and partial response rates were 86 and 14%,
      respectively. CONCLUSIONS: Our data confirmed that PNE was predominant in boys
      and larger family, and similar to the findings for disease prevalence, the number
      of children seeking treatment tended to decrease with increasing age. Low ADH
      levels were recognized as a possible cause of PNE, thereby explaining the good
      response to DDAVP treatment in Taiwanese children with PNE.

PMID- 21898086
TI  - Is it possible to measure peripheral vestibular function in a patient with
      congenital nystagmus?

PMID- 21898085
TI  - SlWRKY70 is required for Mi-1-mediated resistance to aphids and nematodes in
      tomato.
AB  - Plant resistance (R) gene-mediated defense responses against biotic stresses
      include vast transcriptional reprogramming. In several plant-pathogen systems,
      members of the WRKY family of transcription factors have been demonstrated to act
      as both positive and negative regulators of plant defense transcriptional
      networks. To identify the possible roles of tomato (Solanum lycopersicum) WRKY
      transcription factors in defense mediated by the R gene Mi-1 against potato
      aphid, Macrosiphum euphorbiae, and root-knot nematode (RKN), Meloidogyne
      javanica, we used tobacco rattle virus (TRV)-based virus-induced gene silencing
      and transcriptionally suppressed SlWRKY70, a tomato ortholog of the Arabidopsis
      thaliana WRKY70 gene. Silencing SlWRKY70 attenuated Mi-1-mediated resistance
      against both potato aphid and RKN showing that SlWRKY70 is required for Mi-1
      function. Furthermore, we found SlWRKY70 transcripts to be inducible in response
      to aphid infestation and RKN inoculation. Mi-1-mediated recognition of these
      pests modulates this transcriptional response. As previously described for
      AtWRKY70, we found SlWRKY70 transcript levels to be up-regulated by salicylic
      acid and suppressed by methyl jasmonate. This indicates that some aspects of
      WRKY70 regulation are conserved among distantly related eudicots.

PMID- 21898087
TI  - The impact of prelaryngeal node metastases on early glottic cancer treatment
      results.
AB  - The aim of the study was to examine the impact of positive prelaryngeal node on
      the outcome of early glottic cancer and to compare the rate of local and regional
      recurrences and overall survival rates in patients with positive and negative
      Delphian node (DN). In the years 1989-2008, a consecutive cohort of 212 patients
      with T1b and T2 glottic cancer with anterior commisure involvement were treated
      by means of supracricoid partial reconstructive laryngectomies. No adjuvant
      radiotherapy was administered. Out of 212 patients, in 75 suspected prelaryngeal
      tissue was found, harvested and separately sent for histological investigation
      (16-thyroid, 11-fat, 14-connective tissue, 34-lymph nodes). In 137 remaining
      cases, there were only muscles and fascia without even a small amount of tissue
      to be taken. In 16 cases out of the whole group, metastases were found. 33
      patients with positive ultrasound findings on the lateral neck underwent
      selective neck dissection; in 4 cases metastases were confirmed. Local and
      regional recurrence developed in 37 out of 212 patients (17.5%). There was
      significant correlation between local relapse and prelaryngeal node metastases;
      out of 20 cases with local recurrence, 13 had positive DN (P < 0.005). There was
      also significant correlation between nodal relapses and DN metastases; out of 22
      cases with nodal relapse, 12 had positive DN and 10 were DN negative (P < 0.005).
      The organ preservation rates for DN positive and DN negative patients were 62.5
      and 93.88%, respectively. There was noted a significant difference in the mean
      survival between the groups with positive and negative DN (P = 0.004; 38.7 vs.
      49.3 months, respectively). In conclusion, positive DN seems to be a strong
      isolated factor influencing prognosis in patients with early glottic cancer. DN
      metastases are responsible for the increased rates of local and nodal relapses,
      decreased chances of organ preservation and poor overall survival rates.

PMID- 21898088
TI  - Stage progression of congenital cholesteatoma in children.
AB  - This study aimed to investigate the most prevalent stage in each age-group of
      children with congenital cholesteatoma (CC) and verify the correlation between
      the stage and the age of the patients for the type of CC ("closed" keratotic cyst
      and "open" infiltrative types). Patients diagnosed with CC between 2004 and 2009
      (n = 156; 116 boys and 40 girls; mean age, 5 years and 5 months; range, 12 months
      16 years and 7 months) were enrolled retrospectively. Assessment of stage and
      type of CC was performed with preoperative high-resolution temporal bone computed
      tomography and intraoperative findings. The stage of CC was determined using
      Potsic's staging system classified into four stages according to ossicular
      involvement and mastoid extension. The patients consisted of groups divided on
      the basis of a 2-year interval. The prevalence of stage I began to decline from
      the age-group of 1-2 years. In contrast, the prevalence of stages III increased
      from the age-group of 3-4 years and that of stage IV from the age-group 5-6
      years. The prevalence of "open" infiltrative type CC increased from approximately
      the age of 7 years, thus showing some correlation with age but not with stage.
      The prevalence of CC with the advanced stage increased since the age of 2 years.
      Therefore, the importance of early diagnosis and treatment of CC should be more
      emphasized.

PMID- 21898089
TI  - Human equilibrative nucleoside transporter 1 expression is a strong independent
      prognostic factor in UICC T3-T4 pancreatic cancer patients treated with
      preoperative gemcitabine-based chemoradiotherapy.
AB  - BACKGROUND/PURPOSE: We aimed to determine the relationship between the
      intratumoral expression of human equilibrative nucleoside transporter (hENT1),
      the main gemcitabine transporter into cells, and the outcome of gemcitabine-based
      chemoradiotherapy (Gem-CRT) in patients with International Union Against Cancer
      (UICC) T3-T4 pancreatic adenocarcinoma. METHODS: The expressions of hENT1,
      thymidylate synthase (TS), and dihydropyrimidine dehydrogenase were
      immunohistochemically analyzed using the resected specimens from 55 patients (T3,
      38 and T4, 17) who had received curative-intent resection after Gem-CRT. RESULTS:
      The status of hENT1 expression (positive in 39 and negative in 16) was
      significantly associated with "clinical efficacy" (defined as more than 50%
      reduction of the serum carbohydrate antigen [CA] 19-9 level with stable disease
      [SD] or partial response [PR] according to the Response Evaluation Criteria in
      Solid Tumors [RECIST]) for Gem-CRT. The 1- and 3-year overall survival (OS) rates
      were significantly higher in the positive hENT1 expression group (82.9, 39.5%)
      than in the negative expression group (42.9, 14.3%) (p = 0.0037). According to
      combination analysis of hENT1 and TS expressions, the 1- and 3-year OS rates were
      significantly higher in the positive-low combination (89.1, 51.0%) group than in
      the negative-high group (66.7, 0%) (p = 0.023). Multivariate analysis revealed
      that positive hENT1 expression and R0 resection were significant prognostic
      factors for OS. CONCLUSIONS: The hENT1 expression in pancreatic adenocarcinoma
      strongly influences the outcome of preoperative Gem-CRT treatment. This biomarker
      could become a useful predictor of therapeutic effect for gemcitabine-based
      therapy in pancreatic cancer patients.

PMID- 21898090
TI  - Gastrokine 1 functions as a tumor suppressor by inhibition of epithelial
      mesenchymal transition in gastric cancers.
AB  - PURPOSE: Gastrokine 1 (GKN1) plays an important role in the gastric mucosal
      defense mechanism and also acts as a functional gastric tumor suppressor. The
      specific aim of this study was to determine the molecular mechanisms underlying
      GKN1 tumor suppressor activity in the progression of gastric cancers. METHODS: We
      examined the effect of GKN1 on epithelial-mesenchymal transition (EMT) and cell
      migration in GKN1-transfected and recombinant GKN1-treated AGS gastric cancer
      cells using in vitro wound healing, microchemotaxis, and invasion assays.
      RESULTS: In GKN1-transfected AGS cells, we observed inhibition of cell migration
      and invasion in wound healing, transwell and Matrigel assay. Also, GKN1
      transfected and recombinant GKN1-treated AGS cells showed decreased levels of ROS
      and expression of phosphatidylinositol 3-kinase (PI3K)/Akt pathway proteins,
      concomitant with re-expression of E-cadherin and decreased expression of
      cytoplasmic and nuclear expression of beta-catenin, slug, snail, fibronectin, and
      vimentin. CONCLUSIONS: These data suggest that the GKN1 gene may play an
      important role in the progression of sporadic gastric cancers via inhibition of
      EMT and cancer cell migration.

PMID- 21898091
TI  - Wilms' tumor protein 1 (WT1) peptide vaccination in AML patients: predominant TCR
      CDR3beta sequence associated with remission in one patient is detectable in other
      vaccinated patients.
AB  - BACKGROUND: Clinically effective T-cell responses can be elicited by single
      peptide vaccination with Wilms' tumor 1 (WT1) epitope 126-134 in patients with
      acute myeloid leukemia (AML). We recently showed that a predominant T-cell
      receptor (TCR) beta chain was associated with vaccine-induced complete remission
      in an AML patient (patient 1). In this study, we address the question of whether
      this predominant clone or the accompanying Vbeta11 restriction could be found in
      other AML patients vaccinated with the same WT1 peptide. MATERIALS AND METHODS:
      For assessment of Vbeta usage, cytotoxic T lymphocytes (CTLs) from four
      vaccinated patients were divided into specific and non-specific by epitope
      specific enrichment. Vbeta families were quantified in both fractions using
      reverse transcribed quantitative PCR. Vbeta11-positive 'complementary determining
      region 3' (CDR3) sequences were amplified from these samples, from bone marrow
      samples of 17 other vaccination patients, and from peripheral blood of six
      healthy controls, cloned and sequenced. RESULTS: We observed a clear bias towards
      Vbeta11 usage of the WT1-specific CTL populations in all four patients. The
      predominant CDR3beta amino acid (AA) sequence of patient 1 was detected in two
      other patients. CDR3beta loops with closely related AA sequences were only found
      in patient 1. There were no CDR3beta AA sequences with side chains of identical
      chemical properties detected in any patient. CONCLUSION: We provide the first
      data addressing TCR Vbeta chain usage in WT1-specific T-cell populations after
      HLA A*0201-restricted single peptide vaccination. We demonstrate both shared
      Vbeta restriction and the sharing of a TCR beta transcript with proven clinical
      impact in one patient.

PMID- 21898092
TI  - Topiramate and visual loss in a patient carrying a Leber hereditary optic
      neuropathy mutation.
AB  - We describe a 43-year-old patient who experienced visual loss 4 years after
      beginning antiepileptic therapy with topiramate. Ophthalmological and
      neurological examinations led to a preliminary diagnosis of bilateral toxic optic
      neuritis. Mitochondrial genome sequence analysis detected a Leber hereditary
      optic neuropathy 11778G>A mutation. The possibility that topiramate might favor a
      conversion disease, alerts physicians to seek a history of blindness in patients
      undergoing chronic antiepileptic therapy.

PMID- 21898093
TI  - Intermittent Broca's aphasia management in an emergency unit: from theory to
      practice.
AB  - Although Broca's aphasia (BA) may mimic different neurological illness, its
      sudden onset often requires an emergency approach. In this paper, the management
      of a case of intermittent BA occurred in a young woman without history of
      neurological, cardiovascular and arrhythmic diseases is discussed. Diffusion
      weighted magnetic resonance imaging showed two areas of hypoperfusion in the
      terminal branches of the left medial cerebral artery not previously diagnosed by
      computed tomography. Although there were no eligibility criteria for
      thrombolysis, patient received intravenous treatment with recombinant tissue-type
      plasminogen activator (rt-PA) over 1 h and at the end of rt-PA infusion aphasia
      completely disappeared without neurological sequelae. Transesophageal
      echocardiography revealed a thrombus in the left atrial appendage not previously
      detected by transthoracic echocardiography. In the month following the
      cardioembolic stroke, heart rhythm was monitored for 30 days by an external loop
      recorder and during this test two episodes of silent lone atrial fibrillation
      were collected.

PMID- 21898094
TI  - Primary B-cell lymphoma of the cauda equina, successfully treated with high-dose
      methotrexate plus high-dose cytarabine: a case report with MRI findings.
AB  - Primary malignant lymphoma of the cauda equina is an extremely rare disease.
      Previously, there have been only 12 reported cases of malignant lymphoma of the
      cauda equina, and most cases relapsed early in the clinical course. So, the
      optimal treatment strategy for this condition has not been established yet and
      the prognosis is thought to be poor. We experienced a case of B-cell malignant
      lymphoma of the cauda equina, with rapid progression of the muscle weakness of
      the bilateral lower extremities, successfully treated with high-dose methotrexate
      plus high-dose cytarabine (Ara-C) chemotherapy, followed by radiotherapy and in
      complete remission without any recurrence signs, 1.5 years after the initial
      diagnosis. Intrathecal chemotherapy with MTX, Ara-C, and predonisolone was
      simultaneously performed. We should carefully continue to monitor the clinical
      course of our case, with the examinations of magnetic resonance imaging and
      cerebrospinal fluid in order not to overlook any subtle neurological changes or
      other clinical symptoms.

PMID- 21898095
TI  - History of Chiari type I malformation.
AB  - Chiari type I malformation (CIM) was first described in the late 19th Century.
      However, it still raises a great interest among the scientific Community because
      of the increasing number of diagnosed cases, the still unclear pathogenesis and
      natural history and the different options in the surgical management. The present
      review aims at analyzing the centenary history of CIM, starting from the first
      description done by Hans Chiari to the more recent classification, in order to
      introduce such a complex disease and to show the way followed for its assessment
      over the time.

PMID- 21898096
TI  - Natural history of Chiari type I malformation in children.
AB  - The decision on whether or not to operate children with Chiari type I
      malformation (CIM) is difficult and controversial, because of the lack of
      information about the natural evolution of such a disease. Herein, we report on
      the evolution of 16 asymptomatic children with incidentally diagnosed CIM (mean
      age: 6.7 years; mean follow-up: 5.8 years). No patients required suboccipital
      decompression. Thirteen children remained asymptomatic, with stable or improved
      radiological picture (worsening in 2 cases). Three cases showed appearance of
      symptoms: one did not require any treatment; the remaining two underwent
      endoscopic third ventriculostomy because of hydrocephalus, which is a possible
      consequence of CIM. This analysis shows a favorable natural outcome of CIM in
      children, thus suggesting a conservative management in asymptomatic cases.
      However, multicentric studies are required to validate this data.

PMID- 21898097
TI  - One night's CPAP withdrawal in otherwise compliant OSA patients: marked driving
      impairment but good awareness of increased sleepiness.
AB  - PURPOSE: Obstructive sleep apnoea (OSA) patients effectively treated by and
      compliant with continuous positive air pressure (CPAP) occasionally miss a
      night's treatment. The purpose of this study was to use a real car interactive
      driving simulator to assess the effects of such an occurrence on the next day's
      driving, including the extent to which these drivers are aware of increased
      sleepiness. METHODS: Eleven long-term compliant CPAP-treated 50-75-year-old male
      OSA participants completed a 2-h afternoon, simulated, realistic monotonous drive
      in an instrumented car, twice, following one night: (1) normal sleep with CPAP
      and (2) nil CPAP. Drifting out of road lane ('incidents'), subjective sleepiness
      every 200 s and continuous electroencephalogram (EEG) activities indicative of
      sleepiness and compensatory effort were monitored. RESULTS: Withdrawal of CPAP
      markedly increased sleep disturbance and led to significantly more incidents, a
      shorter 'safe' driving duration, increased alpha and theta EEG power and greater
      subjective sleepiness. However, increased EEG beta activity indicated that more
      compensatory effort was being applied. Importantly, under both conditions, there
      was a highly significant correlation between subjective and EEG measures of
      sleepiness, to the extent that participants were well aware of the effects of nil
      CPAP. CONCLUSIONS: Patients should be aware that compliance with treatment every
      night is crucial for safe driving.

PMID- 21898098
TI  - Hypoxemia correlates with attentional dysfunction in patients with obstructive
      sleep apnea.
AB  - PURPOSE: Obstructive sleep apnea is associated with cognitive impairment, but
      whether hypoxemia or repeated arousals and sleepiness are the underlying
      mechanism is controversial. Studies using a wide range of attention and executive
      functions tests in patients with severe sleep apnea are lacking. METHODS: In a
      prospective cohort study, 40 patients aged 30-70 years, diagnosed with
      obstructive sleep apnea (apnea-hypopnea index >=5) were recruited. Patients with
      known cardiovascular, pulmonary, psychiatric, or neurological disease, and or
      patients receiving anti-psychotic, sedatives, or stimulant medications were
      excluded. Patients underwent full overnight polysomnography including continuous
      oxygen saturation measurements followed by extensive neuropsychological testings
      in attention and executive function domains. The correlation between sleep apnea
      severity and patients' performance on the neuropsychological tests was examined.
      RESULTS: The patients' performance on measures of attention and executive
      function was significantly worse compared to the average in a normal population.
      Attention, as reflected by the number of omissions and by the reaction time on
      the Conners' Continuous Performance Test correlated significantly with the apnea
      hypopnea index (r = 0.6, p < 0.001 and r = 0.48, p = 0.003, respectively) and
      with parameters of hypoxemia, namely the average SpO(2) (r = -0.51, p = 0.002 and
      r = -0.39, p = 0.02, respectively) and the percent time spent with SpO(2) < 90%
      (r = 0.57, p < 0.001 and r = 0.39, p = 0.02, respectively), but not with the
      degree of sleepiness. Executive dysfunction did not correlate with sleep
      parameters. DISCUSSION: Attention is the predominant cognitive function affected
      in patients with obstructive sleep apnea and correlates primarily with nocturnal
      hypoxemia rather than daytime sleepiness or sleep fragmentation. Executive
      functions, while below average in some patients, do not correlate with
      polysomnographic parameters.

PMID- 21898099
TI  - Use of micro-CT-based finite element analysis to accurately quantify peri-implant
      bone strains: a validation in rat tibiae.
AB  - Although research has been addressed at investigating the effect of specific
      loading regimes on bone response around the implant, a precise quantitative
      understanding of the local mechanical response close to the implant site is still
      lacking. This study was aimed at validating micro-CT-based finite element (MUFE)
      models to assess tissue strains after implant placement in a rat tibia. Small
      implants were inserted at the medio-proximal site of 8 rat tibiae. The limbs were
      subjected to axial compression loading; strain close to the implant was measured
      by means of strain gauges. Specimen-specific MUFE models were created and
      analyzed. For each specimen, 4 different models were created corresponding to
      different representations of the bone-implant interface: bone and implant were
      assumed fully osseointegrated (A); a low stiffness interface zone was assumed
      with thickness of 40 MUm (B), 80 MUm (C), and 160 MUm (D). In all cases, measured
      and computational strains correlated highly (R (2) = 0.95, 0.92, 0.93, and 0.95
      in A, B, C, and D, respectively). The averaged calculated strains were 1.69,
      1.34, and 1.15 times higher than the measured strains for A, B, and C,
      respectively, and lower than the experimental strains for D (factor = 0.91). In
      conclusion, we demonstrated that specimen-specific FE analyses provide accurate
      estimates of peri-implant bone strains in the rat tibia loading model. Further
      investigations of the bone-implant interface are needed to quantify implant
      osseointegration.

PMID- 21898100
TI  - Time-dependent behavior of cartilage surrounding a metal implant for full
      thickness cartilage defects of various sizes: a finite element study.
AB  - Recently, physiological and biomechanical studies on animal models with metal
      implants filling full-thickness cartilage defects have resulted in good clinical
      outcomes. The knowledge of the time-dependent macroscopic behavior of cartilage
      surrounding the metal implant is essential for understanding the joint function
      after treating such defects. We developed a model to investigate the in vivo time
      dependent behavior of the tibiofemoral cartilages surrounding the metal implant,
      when the joint is subjected to an axial load for various defect sizes. Results
      show that time-dependent effects on cartilage behavior are significant, and can
      be simulated. These effects should be considered when evaluating the results from
      an implant. In particular, the depth into the cartilage where an implant is
      positioned and the mechanical sealing due to solidification of the poroelastic
      material need a time aspect. We found the maximal deformations, contact pressures
      and contact forces in the joint with time for the implant positioned in flush and
      sunk 0.3 mm into the cartilage. The latter position gives the better joint
      performance. The results after 60 s may be treated as the primary results,
      reflecting the effect of accumulation in the joint due to repeated short-time
      loadings. The wedge-shaped implant showed beneficial in providing mechanical
      sealing of cartilages surrounding the implant with time.

PMID- 21898101
TI  - Lansoprazole precipitated QT prolongation and torsade de pointes associated with
      disopyramide.

PMID- 21898102
TI  - Environmental controls on microbial abundance and activity on the greenland ice
      sheet: a multivariate analysis approach.
AB  - Microbes in supraglacial ecosystems have been proposed to be significant
      contributors to regional and possibly global carbon cycling, and quantifying the
      biogeochemical cycling of carbon in glacial ecosystems is of great significance
      for global carbon flow estimations. Here we present data on microbial abundance
      and productivity, collected along a transect across the ablation zone of the
      Greenland ice sheet (GrIS) in summer 2010. We analyse the relationships between
      the physical, chemical and biological variables using multivariate statistical
      analysis. Concentrations of debris-bound nutrients increased with distance from
      the ice sheet margin, as did both cell numbers and activity rates before reaching
      a peak (photosynthesis) or a plateau (respiration, abundance) between 10 and 20
      km from the margin. The results of productivity measurements suggest an overall
      net autotrophy on the GrIS and support the proposed role of ice sheet ecosystems
      in carbon cycling as regional sinks of CO(2) and places of production of organic
      matter that can be a potential source of nutrients for downstream ecosystems.
      Principal component analysis based on chemical and biological data revealed three
      clusters of sites, corresponding to three 'glacier ecological zones', confirmed
      by a redundancy analysis (RDA) using physical data as predictors. RDA using data
      from the largest 'bare ice zone' showed that glacier surface slope, a proxy for
      melt water flow, accounted for most of the variation in the data. Variation in
      the chemical data was fully explainable by the determined physical variables.
      Abundance of phototrophic microbes and their proportion in the community were
      identified as significant controls of the carbon cycling-related microbial
      processes.

PMID- 21898103
TI  - Soil and cultivar type shape the bacterial community in the potato rhizosphere.
AB  - The rhizospheres of five different potato cultivars (including a genetically
      modified cultivar) obtained from a loamy sand soil and two from a sandy peat
      soil, next to corresponding bulk soils, were studied with respect to their
      community structures and potential function. For the former analyses, we
      performed bacterial 16S ribosomal RNA gene-based PCR denaturing gradient gel
      electrophoresis (PCR-DGGE) on the basis of soil DNA; for the latter, we extracted
      microbial communities and subjected these to analyses in phenotype arrays (PM1,
      PM2, and PM4, Biolog), with a focus on the use of different carbon, sulfur and
      phosphorus sources. In addition, we performed bacterial PCR-DGGE on selected
      wells to assess the structures of these substrate-responsive communities. Effects
      of soil type, the rhizosphere, and cultivar on the microbial community structures
      were clearly observed. Soil type was the most determinative parameter shaping the
      functional communities, whereas the rhizosphere and cultivar type also exerted an
      influence. However, no genetically modified plant effect was observed. The
      effects were imminent based on general community analysis and also single
      compound analysis. Utilization of some of the carbon and sulfur sources was
      specific per cultivar, and different microbial communities were found as defined
      by cultivar. Thus, both soil and cultivar type shaped the potato root-associated
      bacterial communities that were responsive to some of the substrates in phenotype
      arrays.

PMID- 21898104
TI  - Effects of cumulus cells removal after 6 h co-incubation of gametes on the
      outcomes of human IVF.
AB  - PURPOSE: To investigate the effects of cumulus cells removal after 6 h co
      incubation of gametes on the fertilization, polyspermy, multinucleation and
      clinical pregnancy rates in human IVF. METHODS: A total of 1,200 IVF-ET cycles
      undergoing 6 h co-incubation of gametes in 2009 were included in this study.
      Inclusion criteria were: female age <38 years, first IVF treatment, with bi-ovary
      and normal ovarian response, e.g., 4 ~ 20 oocytes could be obtained. A 6 h period
      of co-incubation was applied in all IVF cycles. According to the history of
      infertility, cumulus cells were mechanically removed either 6 h post-insemination
      or 20 h post-insemination. For couples with primary infertility, or unexplained
      infertility, or mild oligospermia or asthenospermia, the cumulus cells were
      removed at 6 h of insemination for the polar body observation (6 h group, n =
      565). Of these, 80 cycles received early rescue ICSI due to fertilization failure
      or low fertilization rate at 6 h of insemination. For couples with secondary
      infertility and normal semen analysis, the cumulus cells were removed at 20 h of
      insemination as routine (20 h group, n = 635). Of these, three cycles received
      late rescue ICSI due to fertilization failure at 20 h of insemination. Normal
      fertilization, polyspermy (>=3PN), multinucleation and clinical pregnancy rates
      were compared between the two groups (rescue ICSI cycles were not included in the
      comparison in both groups). RESULTS: Significant difference (P < 0.05) was
      observed between the groups regarding polyspermy rates (7.48% in 6 h group and
      9.22% in 20 h group). No difference was observed between the groups regarding
      normal fertilization rates (2PN rate) (64.89% in 6 h group and 65.74% in 20 h
      group). No difference was observed between the groups regarding multinucleation
      and clinical pregnancy rates (11.01% and 65.15% in 6 h group, 10.75% and 66.93%
      in 20 h group, respectively). The clinical pregnancy rate was 51.43% in cycles
      receiving early rescue ICSI, while no clinical pregnancy was obtained in cycles
      receiving late rescue ICSI. CONCLUSION: The present results indicate that cumulus
      cells removal at 6 h of insemination is a relatively safe operation, which
      yielded comparable normal fertilization rate, multinucleation and clinical
      pregnancy rates compared with 20 h group. This protocol may be beneficial for
      early obsevation of fertilization failure and make early rescue ICSI possible.

PMID- 21898105
TI  - Genome instability in AZFc region on Y chromosome in leukocytes of fertile and
      infertile individuals following exposure to gamma radiation.
AB  - PURPOSE: Men are exposed to various doses of ionizing radiation due to living in
      regions with high natural background radiation, accidentally, occupationally or
      for cancer treatment. To study genomic instability of AZFc region to gamma
      radiation, blood samples from normal, oligozoospermia, and azoospermia
      individuals were irradiated by a Co-60 source. METHODS: Irradiated cells were
      kept for 48 h in order to repair initial DNA damages. Real time PCR was performed
      for three markers (SY 1206, SY 1197, SY 579) for testing copy number variation
      before and after irradiation. Copy number variations were compared by calculation
      of cycle threshold comparative method. RESULTS: Copy number variations of studied
      markers in AZFc region (microdeletion and duplication) in all samples after
      exposure to radiation increased with a dose dependent fashion. The frequency of
      instability was significantly higher in samples from infertile men in comparison
      with fertile ones (p < 0.001). CONCLUSION: No significant difference was seen
      between the two infertile groups (p > 0.05). This observation might be a possible
      explanation for induction of azoospermia and oligozoospermia after radiotherapy.
      Increased frequency of induced microdeletion and duplication in infertile men
      compared with normal might be attributed to the deficiency in repair systems and
      the genetic factors involved in incomplete spermatogenesis of infertile men.

PMID- 21898106
TI  - Permissible value for vanadium in allitic udic ferrisols based on physiological
      responses of green Chinese cabbage and soil microbes.
AB  - Greenhouse experiments were conducted to study the permissible value of vanadium
      (V) based on the growth and physiological responses of green Chinese cabbage
      (Brassica chinensis L.), and effects of V on microbial biomass carbon (MBC) and
      enzyme activities in allitic udic ferrisols were also studied. The results showed
      that biomass of cabbage grown on soil treated with 133 mg V kg(-1) significantly
      decreased by 25.1% compared with the control (P < 0.05). Vanadium concentrations
      in leaves and roots increased with increasing soil V concentration. Contents of
      vitamin C (Vc) increased by 10.3%, while that of soluble sugar in leaves
      significantly decreased by 54.0% when soil V concentration was 133 mg kg(-1),
      respectively. The uptake of essential nutrient elements by cabbage was disturbed
      when soil V concentration exceeded 253 mg kg(-1). Soil MBC was significantly
      stimulated by 15.5%, while dehydrogenase activity significantly decreased by
      62.8% and urease activity slightly changed at treatment of 133 mg V kg(-1) as
      compared with the control, respectively. Therefore, the permissible value of V in
      allitic udic ferrisols is proposed as 130 mg kg(-1).

PMID- 21898107
TI  - Serum selenium concentration in liver cirrhotic patients suffering from hepatitis
      B and C in Pakistan.
AB  - High rates of hepatitis B and C are present in Pakistan. Epidemiological surveys
      demonstrated an inverse association between selenium (Se) level and regional
      cancer incidence, as well as viral infection. In this cross-sectional descriptive
      analytical study, serum selenium concentration of 150 patients suffering from
      hepatitis B and C patients, along with 26 healthy controls, was determined by
      atomic absorption spectrophotometer equipped with hydride generation system. The
      mean and standard deviation of serum selenium concentration observed in male and
      female patients with hepatitis C were 101.60 +/- 0.55 and 77.43 +/- 0.47 MUg/l,
      respectively, while the mean and standard deviation of serum selenium
      concentration observed in male and female patients with hepatitis B was 107.58 +/
      0.44 and 137.8 +/- 0.36 MUg/l. Analysis of t test showed significant difference
      between hepatitis C and B (P < 0.001) patients in serum selenium concentration
      when compared with control.

PMID- 21898108
TI  - P-wave dispersion in children with acute rheumatic fever.
AB  - As a new and simple electrocardiographic marker, P-wave dispersion is reported to
      be associated with inhomogeneous and discontinuous propagation of sinus impulses.
      The current study aimed to investigate P-wave dispersion in children with acute
      rheumatic fever. The study population consisted of 47 children with acute
      rheumatic fever (29 patients with carditis and 18 patients without carditis) and
      31 healthy control subjects. Maximum and minimum P-wave durations were measured
      from the 12-lead surface electrocardiogram. The P-wave dispersion was calculated
      as the difference between maximum and minimum P-wave durations. The maximum P
      wave duration and the P-wave dispersion of the patients with and without carditis
      were significantly greater than those of the control subjects. The P-wave
      dispersion of the patients with carditis was significantly greater than that of
      the patients without carditis. In conclusion, the P-wave dispersion was higher in
      the children with acute rheumatic fever than in the healthy control subjects.

PMID- 21898109
TI  - Anti-tumor effects of all-trans retinoic acid are enhanced by genistein.
AB  - The effects of all-trans retinoic acid (ATRA) on cancer are complex. ATRA has
      anti-cancer effects as it promotes cancer cell differentiation. However, ATRA
      also up-regulates expression of vascular endothelial growth factor (VEGF) in
      cancer cells, which leads to angiogenesis and can, thus, facilitate cancer
      growth. Genistein, a crucial non-nutrient component in soybean, exhibits anti
      cancer effects by inhibiting protein tyrosine kinase that is involved in up
      regulation of VEGF. We hypothesized that genistein, applied simultaneously with
      ATRA, would counter its undesired angiogenic effects and, thus, enhance the anti
      cancer effects of ATRA. The purpose of this study was to document potential
      synergistic effects of genistein and ATRA in A549 lung adenocarcinoma cells. We
      further explored the role of genistein on countering the ATRA-induced VEGF
      expression. We demonstrate that genistein enhances the ATRA-induced growth
      inhibition of A549 cells by promoting apoptosis. Further, the combined use of
      ATRA and genistein leads to cancer cell arrest in G0/G1 and G2/M cell cycle
      phases. Finally, expression of VEGF (both mRNA and protein) was diminished in
      A549 cells exposed to both ATRA and genistein. In conclusion, our results
      demonstrate that genistein effectively enhances anti-cancer effects of ATRA,
      particularly, by countering the ATRA-induced up-regulation of VEGF. Our study
      provides an experimental basis for combined use of ATRA and genistein in the
      treatment of lung cancer.

PMID- 21898110
TI  - Bifurcation of orbits and synchrony in inferior olive neurons.
AB  - Inferior olive neurons (IONs) have rich dynamics and can exhibit stable,
      unstable, periodic, and even chaotic trajectories. This paper presents an
      analysis of bifurcation of periodic orbits of an ION when its two key parameters
      (a, MU) are varied in a two-dimensional plane. The parameter a describes the
      shape of the parabolic nonlinearity in the model and MU is the extracellular
      stimulus. The four-dimensional ION model considered here is a cascade connection
      of two subsystems (S(a) and S(b)). The parameter plane (a - MU) is delineated
      into several subregions. The ION has distinct orbit structure and stability
      property in each subregion. It is shown that the subsystem S(a) or S(b) undergoes
      supercritical Poincare-Andronov-Hopf (PAH) bifurcation at a critical value
      MU(c)(a) of the extracellular stimulus and periodic orbits of the neuron are
      born. Based on the center manifold theory, the existence of periodic orbits in
      the asymptotically stable S(a), when the subsystem S(b) undergoes PAH
      bifurcation, is established. In such a case, both subsystems exhibit periodic
      orbits. Interestingly when S(b) is under PAH bifurcation and S(a) is unstable,
      the trajectory of S(a) exhibits periodic bursting, interrupted by periods of
      quiescence. The bifurcation analysis is followed by the design of (i) a linear
      first-order filter and (ii) a nonlinear control system for the synchronization of
      IONs. The first controller uses a single output of each ION, but the nonlinear
      control system uses two state variables for feedback. The open-loop and closed
      loop responses are presented which show bifurcation of orbits and synchronization
      of oscillating neurons.

PMID- 21898111
TI  - Incorporating chemical signalling factors into cell-based models of growing
      epithelial tissues.
AB  - In this paper we present a comprehensive computational framework within which the
      effects of chemical signalling factors on growing epithelial tissues can be
      studied. The method incorporates a vertex-based cell model, in conjunction with a
      solver for the governing chemical equations. The vertex model provides a natural
      mesh for the finite element method (FEM), with node movements determined by force
      laws. The arbitrary Lagrangian-Eulerian formulation is adopted to account for
      domain movement between iterations. The effects of cell proliferation and
      junctional rearrangements on the mesh are also examined. By implementing
      refinements of the mesh we show that the finite element (FE) approximation
      converges towards an accurate numerical solution. The potential utility of the
      system is demonstrated in the context of Decapentaplegic (Dpp), a morphogen which
      plays a crucial role in development of the Drosophila imaginal wing disc. Despite
      the presence of a Dpp gradient, growth is uniform across the wing disc. We make
      the growth rate of cells dependent on Dpp concentration and show that the number
      of proliferation events increases in regions of high concentration. This allows
      hypotheses regarding mechanisms of growth control to be rigorously tested. The
      method we describe may be adapted to a range of potential application areas, and
      to other cell-based models with designated node movements, to accurately probe
      the role of morphogens in epithelial tissues.

PMID- 21898112
TI  - Characterization of Candida sp. NY7122, a novel pentose-fermenting soil yeast.
AB  - Yeasts that ferment both hexose and pentose are important for cost-effective
      ethanol production. We found that the soil yeast strain NY7122 isolated from a
      blueberry field in Tsukuba (East Japan) could ferment both hexose and pentose (D
      xylose and L-arabinose). NY7122 was closely related to Candida subhashii on the
      basis of the results of molecular identification using the sequence in the D1/D2
      domains of 26S rDNA and 5.8S-internal transcribed spacer region. NY7122 produced
      at least 7.40 and 3.86 g l-1 ethanol from 20 g l-1 D-xylose and L-arabinose
      within 24 h. NY7122 could produce ethanol from pentose and hexose sugars at 37
      degrees C. The highest ethanol productivity of NY7122 was achieved under a low pH
      condition (pH 3.5). Fermentation of mixed sugars (50 g l-1 glucose, 20 g l-1 D
      xylose, and 10 g l-1 L-arabinose) resulted in a maximum ethanol concentration of
      27.3 g l-1 for the NY7122 strain versus 25.1 g l-1 for Scheffersomyces stipitis.
      This is the first study to report that Candida sp. NY7122 from a soil environment
      could produce ethanol from both D-xylose and L-arabinose.

PMID- 21898113
TI  - Catechol-O-methyltransferase genotype (Val158met) modulates cancer-related
      fatigue and pain sensitivity in breast cancer survivors.
AB  - Cancer-related fatigue and pain after surgery are the most frequent and most
      incapacitating cancer-related symptoms after breast cancer treatment. Genetic
      influence of cancer-related fatigue and pain has not been previously
      investigated. Our aim was to examine the influence of catechol-O
      methyltransferase (COMT) Val158Met genotypes on cancer-related fatigue, post
      mastectomy pain, and pressure pain hypersensitivity in breast cancer survivors.
      One-hundred and twenty-eight (n = 128) breast cancer survivors who were treated
      with radiotherapy and chemotherapy participated in this study. After amplifying
      Val158Met polymorphisms by polymerase chain reaction, COMT genotype was divided
      into Val/Val, valine/methionine (Val/Met), or Met/Met. The Piper fatigue scale
      (PFS) was used to assess cancer-related fatigue. Neck and shoulder/axillary pain
      intensity was assessed with a numerical pain rate scale (0-10). Finally, pressure
      pain thresholds (PPT) were assessed bilaterally over the C5-C6 zygapophyseal
      joints, deltoid muscles, second metacarpal, and tibialis anterior muscles. Breast
      cancer survivors carrying the Met/Met genotype reported higher levels of fatigue
      (all subscales, P < 0.001), higher neck pain intensity, and lower PPT over C5-C6
      joints and deltoid muscles (all, P < 0.001) relative to those with Val/Met or
      Val/Val genotypes. The results suggest that breast cancer survivors carrying the
      Met/Met genotype exhibit higher fatigue, neck pain, and pressure pain
      hypersensitivity over the neck and shoulder area. This study is important because
      it strives to understand the factors that predispose some breast cancer survivors
      to more cancer-related fatigue and increased pain sensitivity.

PMID- 21898114
TI  - Phase II trial of a novel capecitabine dosing schedule in combination with
      lapatinib for the treatment of patients with HER2-positive metastatic breast
      cancer.
AB  - Our group applied mathematical modeling to capecitabine dosing and predicted 7
      days of treatment followed by 7 days of rest (7-7) would improve efficacy and
      minimize toxicity. The conventional schedule of capecitabine limits full dosing
      in combination with other agents due to toxicity. Lapatinib inhibits the tyrosine
      kinase of HER2 and has activity when added to conventionally scheduled
      capecitabine for the treatment of patients with trastuzumab-refractory, HER2
      positive, metastatic breast cancer (MBC). We performed this study to evaluate the
      activity and tolerability of capecitabine 7-7 with lapatinib in patients with
      trastuzumab-refractory MBC. Eligible patients had measurable, HER2-positive, MBC
      that progressed following exposure to trastuzumab. Treatment consisted of
      capecitabine 2,000 mg orally twice daily, 7-7 and lapatinib 1,250 mg orally
      daily. The primary endpoint was response rate. Secondary endpoints included
      toxicity, progression-free survival, and stable disease >= 6 months. Twenty-three
      patients were treated on study. More than 60% had prior chemotherapy for MBC and
      all had prior trastuzumab. After a median of 23 weeks (range 2-96+), five
      patients had partial responses (23; 95 CI, 7-44%) and six (27; 95 CI, 10-48%) had
      stable disease >= 6 months. Median progression-free survival was 9.4 months. The
      most common treatment-related toxicities >= grade (gr) 2 were hand-foot syndrome
      (gr 2 43%; gr 3 4% gr 4 0%), diarrhea (gr 2 26%; gr 3/4 0%), elevated liver
      chemistries (gr 2 17%; gr 3/4 0%), and anemia (gr 2 13%; gr 3 4%; gr 4 4%). No
      grade >= 3 nausea, vomiting, or diarrhea events occurred. This study demonstrated
      feasibility and after meeting biostatistical requirements for continued accrual
      was terminated in anticipation of slow enrollment. Capecitabine 7-7 with
      lapatinib was well tolerated with minimal gastrointestinal toxicity. Antitumor
      activity was observed in patients with trastuzumab-refractory MBC.

PMID- 21898115
TI  - Aspirin use and breast cancer risk: a meta-analysis.
AB  - Animal and in vitro studies suggest that the use of aspirin may be associated
      with reduced risk for breast cancer, but results from these studies of the
      association have been inconsistent. The objective of this meta-analysis was to
      quantitatively summarize the current evidence for such a relationship. We
      searched MEDLINE for studies of aspirin use and breast cancer risk that were
      published in any language, from January 1, 1966, to July 1, 2011. A total of 33
      studies (19 cohort studies, 13 case-control studies, and 1 randomized controlled
      trial [RCT]) that included 1,916,448 subjects were identified. We pooled the
      relative risks from individual studies using a random-effects model,
      heterogeneity, and publication bias analyses. In a pooled analysis of all
      studies, aspirin use was associated with reduced risk for breast cancer (odds
      ratio [OR] = 0.86, 95% confidence interval [CI] = 0.81, 0.92). In the subgroup
      analysis by study design, results were similar except for RCT (OR = 0.98, 95% CI
      = 0.87, 1.09). In conclusion, this meta-analysis indicated that regular use of
      aspirin may be associated with reduced risk of breast cancer. More RCT were
      needed to confirm this association in the future.

PMID- 21898117
TI  - Relationship between the trochlear groove angle and patellar cartilage morphology
      defined by 3D spoiled gradient-echo imaging.
AB  - OBJECTIVE: To examine whether the femoral trochlear groove angle (TGA) is a
      determinant of the patellar cartilage volume and patellar cartilage damage.
      MATERIALS AND METHODS: Patellar cartilage was evaluated by MR imaging in 66
      patients (22 males and 44 females) with knee pain. Fat-suppressed 3D spoiled
      gradient-echo images were used to calculate the cartilage volume and to grade the
      cartilage damage. The proximal and distal TGAs were measured from axial PD
      weighted FSE MR images with fat suppression. RESULTS: For every increase in the
      TGA at the distal femur, the patellar cartilage volume was significantly
      increased by 6.07 * 10(-3) cm(3) (95% CI: 1.27 * 10(-3), 10.9 * 10(-3)) after
      adjustment for age, gender, and patellar bone volume (P < 0.05). The MR grade of
      medial patellar cartilage damage progressed as the distal TGA became narrower,
      although there was no significant correlation between the distal TGA and the MR
      grading of patellar cartilage damage. CONCLUSION: A more flattened distal TGA was
      associated with increased patellar cartilage volume. However, there was no
      association between TGA and patellar cartilage defects.

PMID- 21898116
TI  - Should beta blockers no longer be considered first-line therapy for the treatment
      of essential hypertension without comorbidities?
AB  - Although most guidelines committees historically recommended initial diuretics
      and/or beta blockers for uncomplicated hypertension, clinical trial outcomes
      analyzed in the last 5 to 7 years have been suboptimal with atenolol, the world's
      most popular beta blocker. Several meta-analyses have suggested that despite
      lowering blood pressure, any and all beta blockers inadequately protect
      hypertensive patients from cardiovascular events. These phenomena have been
      attributed to ineffective lowering of central aortic or inter-visit blood
      pressures, or adverse metabolic effects (particularly when combined with
      diuretics). Although there has never been a head-to-head comparison of atenolol
      with any other beta blocker in hypertensive patients, indirect comparisons can be
      done with network and Bayesian meta-analyses, which suggest that heterogeneity of
      beta-blockers' pharmacology also extends to outcomes. Although once-daily
      atenolol as initial antihypertensive therapy may be unwise, whether initial beta
      blockers newer than atenolol reduce cardiovascular risk to the same extent as
      other antihypertensive drugs should be answered with more clinical trials.

PMID- 21898118
TI  - Evaluation of surfactants as solubilizing agents in microsomal metabolism
      reactions with lipophilic substrates.
AB  - Solubilizing agents are routinely added when investigating the biotransformation
      of lipophilic substrates using hepatic microsomes. For highly lipophilic
      compounds, the concentration of solvent or surfactant necessary for dissolution
      can be detrimental to enzyme activity. This study evaluates the effect of 12
      surfactants on microsomal metabolism and the ability of the same surfactants to
      improve the aqueous solubility of the pentabrominated diphenyl ether BDE-100, a
      lipophilic environmental contaminant previously found to be recalcitrant to in
      vitro metabolism. Of the surfactants investigated, Cremophor EL and Tween 80
      displayed the best combination of increased BDE-100 solubility and minimal
      inhibition of microsomal metabolism. However, a comparison of the in vitro
      metabolism products of BDE-100 in the presence of the two surfactants revealed
      varying amounts of metabolites depending on the surfactant used.

PMID- 21898119
TI  - Use of parenteral colistin for the treatment of multiresistant Gram-negative
      organisms in major burn patients in South Korea.
AB  - PURPOSE: To assess the therapeutic effect and toxicity of intravenous colistin in
      the treatment of multidrug-resistant (MDR) Gram-negative bacteria in patients
      with severe burns. METHODS: The medical records of 930 patients admitted to the
      Burn Intensive Care Unit (ICU) at Hallym University Hangang Sacred Heart
      Hospital, Seoul, South Korea between April 2007 and December 2009 were
      retrospectively reviewed. Of these, the 104 patients who had received intravenous
      colistin treatments (104 courses) during this period were enrolled in the study.
      Changes in creatinine level were analyzed in three groups: all patients receiving
      colistin (n = 104), patients with undergoing continuous renal replacement therapy
      (CRRT group; n = 38), and patients not undergoing CRRT (non-CRRT group; n = 66).
      RESULTS: Among these patients, the burnt body surface area ranged from 5 to 96%
      (mean 49.7%). Thirty-five patients (33.7%) suffered inhalation injury, and CRRT
      was administered to 38 patients. The mean duration of colistin treatment was 14.7
      (range 4-71) days. The total dose of colistin was 3,045.7 mg (range 100-13,800).
      The length of ICU stay was 48.9 (range 7-154) days. Forty patients (38.5%) died.
      The mean pre-colistin creatinine level of all patients was 1.04 mg/dL, and the
      mean post-colistin level was 1.34 mg/dL. The mean pre-colistin creatinine level
      of the CRRT group and non-CRRT group was 1.68 and 0.66 mg/dL, and the mean post
      colistin level was 1.68 and 1.14 mg/dL, respectively. CONCLUSIONS: Colistin
      appears to be a relatively safe and effective treatment for major burn patients
      with infections caused by MDR Gram-negative bacteria when no other drug is
      available. Additionally, we found no statistically significant impairment of
      creatinine levels.

PMID- 21898120
TI  - Combination therapy with an aminoglycoside for Staphylococcus aureus endocarditis
      and/or persistent bacteremia is associated with a decreased rate of recurrent
      bacteremia: a cohort study.
AB  - PURPOSE: Although limited data exist on the efficacy and potential risk of
      synergistic aminoglycoside therapy for persistent Staphylococcus aureus
      bacteremia and endocarditis, aminoglycosides are frequently used in clinical
      practice. METHODS: As our study population, we included subjects fulfilling the
      modified Duke criteria for S. aureus endocarditis and/or having greater than 72 h
      of S. aureus bacteremia. Among these subjects, we compared patients who did and
      did not receive aminoglycoside therapy for their S. aureus bloodstream infection.
      These groups were compared for the primary outcome of recurrent bacteremia, as
      well as for the duration of bacteremia, mortality, complication rate, and
      incident renal failure. RESULTS: Eighty-seven subjects fulfilled the inclusion
      criteria. Of these, 49 received aminoglycoside therapy, whereas 38 did not. There
      were no significant differences in the baseline characteristics when comparing
      groups who did or did not receive aminoglycoside therapy. Four (8.2%) subjects
      treated with aminoglycoside therapy experienced recurrent bacteremia versus nine
      (23.7%) who did not receive aminoglycoside therapy [relative risk and 95%
      confidence interval [RR (95%CI)] = 0.51 (0.22-1.17), p = 0.04]. In multivariable
      analyses, aminoglycoside use remained significantly associated with a decrease in
      recurrent bacteremia [adjusted odds ratio (OR) (95%CI) = 0.26 (0.07-0.98), p =
      0.046]. No significant differences were seen between groups treated with and
      without an aminoglycoside in terms of the 6-month all-cause mortality (51.0 vs.
      42.1%, p = 0.41), complication rate (71.4 vs. 73.7%, p = 0.82), or incident renal
      failure (54.5 vs. 46.9%, p = 0.54). CONCLUSIONS: The use of combination therapy
      with an aminoglycoside in persistent S. aureus bacteremia and/or endocarditis may
      be associated with a lower rate of recurrent bacteremia without significant
      differences in the incident renal failure.

PMID- 21898122
TI  - Expression, localization, and phosphorylation of Akt1 in benign and malignant
      thyroid lesions.
AB  - The serine/threonine protein kinase Akt is a key molecule in the phosphatidyl
      inositol 3-kinase pathway that is often overactivated in human cancers. Three Akt
      isoforms (Akt1, Akt2, Akt3) have been identified in human cells and they show
      different distribution and have non-redundant functions. The aim of this study
      was to determine whether the expression, phosphorylation, and localization of
      Akt1 isoform in human thyroid malignant lesions are different from those in
      benign lesions. Nuclear and cytoplasmic fractions were isolated from tissue
      samples and Western blot method was used to detect Akt1 presence in both cellular
      fractions. Akt1 expression was also assessed by ELISA method. To estimate Akt1
      phosphorylation, kinase was immunoprecipitated from cell lysates and tested with
      anti-phospho-Akt antibodies. The Akt1 expression in majority of thyroid cancer
      samples was significantly higher than in benign lesions (p < 0.05). Akt1 both in
      differentiated cancers (follicular and papillary) and benign lesions was
      localized mainly in cytoplasmic fraction. In two of three anaplastic cancer
      samples Akt1 was predominantly localized in nucleus. The ratio of phosphorylated
      Akt1 to total Akt1 was lower in cancers than in non-neoplastic lesions and
      adenomas. Thus, although Akt1 seems to be overexpressed in thyroid neoplasms, its
      high phosphorylation is not characteristic for thyroid cancers.

PMID- 21898121
TI  - Under-notification of cryptosporidiosis by routine clinical and laboratory
      practices among non-hospitalised children with acute diarrhoea in Southern Spain.
AB  - INTRODUCTION: In a prevalence study of 400 stool samples from non-hospitalised
      children under 7 years of age with diarrhoea, the presence of Cryptosporidium was
      evaluated. METHODS: In addition to standard microbiological analyses used for
      testing for bacteria, parasites, adenoviruses and reoviruses, all samples were re
      evaluated for the presence of Cryptosporidium by means of microscopy using a
      modified acid-fast staining technique, a rapid immunoassay for the qualitative
      detection of C. parvum and Giardia lamblia, the ImmunoCard STAT! test, and nested
      polymerase chain reaction (PCR). For identifying the genotypes of
      Cryptosporidium, the gene 18S ssu rRNA was amplified and sequenced. RESULTS:
      Thirty-two samples were positive by microscopy, 26 by immunoassay and 61 by
      nested PCR. Twenty-seven of these organisms were identified as Cryptosporidium
      hominis, 31 as Cryptosporidium parvum and, in four samples, it was impossible to
      identify the species. C. parvum was significantly more frequent in girls and C.
      hominis was significantly more frequent in boys (Fisher's exact test, p = 0.034).
      Although Cryptosporidium is only notified in a very small number of patients (1
      4%) with diarrhoea in Spain, the microorganism was identified by nested PCR in
      15.1% of the samples. CONCLUSION: This study, therefore, highlights the under
      notification of infections caused by Cryptosporidium in Southern Spain and poses
      the question of whether its routine testing should be carried out in cases of
      gastroenteritis in children.

PMID- 21898123
TI  - The age at motor symptoms onset in LRRK2-associated Parkinson's disease is
      affected by a variation in the MAPT locus: a possible interaction.
AB  - The current paradigm on Parkinson's disease (PD) pathogenesis and course suggests
      the involvement of multiple genes and the interaction between them. Recently, it
      was reported that a variation (rs2435207) in the MAPT gene region influenced the
      age of motor symptoms onset (AO) in 44 PD patients from 19 families, carriers of
      leucine-rich repeat kinase 2 (LRRK2) mutations, all of European and North
      American origin. To examine whether genetic factors within the MAPT locus exert a
      similar effect on AO in a different population of LRRK2-associated PD patients,
      99 unrelated Ashkenazi patients with the LRRK2 p.G2019S mutation were analyzed.
      Three SNPs in the MAPT region were studied, rs393152, rs2435207, and rs11079727;
      the latter is located in the first intron of MAPT. Among carriers of the single
      LRRK2 p.G2019S mutation that did not carry a founder Ashkenazi GBA mutation too
      (n = 84), the AO in minor rs11079727 A allele carriers (C/A genotype) was
      significantly older (62.5 +/- 10.6 years) compared to the AO (55.7 +/- 11.6)
      among carriers of the C/C genotype (p = 0.025). Our results further support a
      possible interaction between genetic factors in the MAPT region and the LRRK2
      gene, which influence the clinical course of PD patients.

PMID- 21898124
TI  - Pituitary adenylate cyclase-activating polypeptide causes increased tyrosine
      phosphorylation of focal adhesion kinase and paxillin.
AB  - The effects of pituitary adenylate cyclase-activating polypeptide (PACAP) on
      tyrosine phosphorylation of focal adhesion kinase (FAK) and paxillin were
      investigated using lung cancer cells. Addition of PACAP-27 or PACAP-38 but not
      vasoactive intestinal peptide to NCI-H838 or NCI-H1299 human lung cancer cells
      significantly increased the tyrosine phosphorylation of FAK or paxillin. The
      increase in FAK or paxillin tyrosine phosphorylation caused by addition of PACAP
      27 to NCI-H838 cells was inhibited by PACAP(6-38), a PAC1-receptor (R)
      antagonist. The increase in FAK or paxillin tyrosine phosphorylation caused by
      100 nM PACAP-27 was maximal 2 min after addition to NCI-H838 cells. The effects
      of PACAP at stimulating FAK and paxillin tyrosine phosphorylation were reversed
      by cytochalasin D and genistein which inhibit actin polymerization and tyrosine
      kinase activity, respectively. The effects of PACAP at stimulating FAK and
      paxillin tyrosine phosphorylation were reversed by U-73122 but not H89 which
      inhibit phospholipase C and protein kinase A, respectively. The results show that
      PAC1-R regulates FAK and paxillin tyrosine phosphorylation in lung cancer cells
      as a result of increased phosphatidylinositol turnover but not adenylyl cylase
      stimulation.

PMID- 21898127
TI  - Characterization of a beta-glucosidase from Sulfolobus solfataricus for
      isoflavone glycosides.
AB  - The specific activity of a recombinant beta-glucosidase from Sulfolobus
      solfataricus for isoflavones was: daidzin > glycitin > genistin > malonyl
      genistin > malonyl daidzin > malonyl glycitin. The hydrolytic activity of this
      enzyme for daidzin was highest at pH 5.5 and 90 degrees C with a half-life of 18
      h, a K (m) of 0.5 mM, and a k (cat) of 2532 s(-1). The enzyme converted 1 mM
      daidzin to 1 mM daidzein after 1 h with a molar yield of 100% and a productivity
      of 1 mM h(-1). Among beta-glucosidases, that from S. solfataricus beta had the
      highest thermostability, k (cat), k (cat)/K (m), conversion yield, and
      productivity in the hydrolysis of daidzin.

PMID- 21898126
TI  - Miglitol administered before breakfast increased plasma active glucagon-like
      peptide-1 (GLP-1) levels after lunch in patients with type 2 diabetes treated
      with sitagliptin.
AB  - We recently reported that the administration of miglitol alone just before
      breakfast improved postprandial hyperglycemia and increased active glucagon-like
      peptide-1 (GLP-1) levels after lunch in men without diabetes. Miglitol and
      dipeptidyl peptidase-4 inhibitors, such as sitagliptin, enhance plasma active GLP
      1 concentrations via different mechanisms; therefore, combined therapy with these
      agents was more effective than monotherapy. In this study, we compared the
      effectiveness of the administration of miglitol alone just before breakfast on
      the plasma glucose, serum insulin and glucagon, and plasma incretin levels in
      sitagliptin-treated patients with type 2 diabetes. We measured the plasma
      glucose, serum insulin and glucagon, plasma active GLP-1, and total glucose
      dependent insulinotropic polypeptide levels before breakfast, at 120 min after
      breakfast, before lunch, and 60 and 120 min after lunch in patients with diabetes
      who are receiving sitagliptin. This trial was performed for the following 2 days
      on each subject (Day 1: no miglitol, Day 2: miglitol alone [50 mg] administered
      just before breakfast). The area under the curve (AUC) of the plasma glucose
      levels after lunch in the miglitol-treated group tended to be lower than that in
      the miglitol-untreated group, but the difference was not statistically
      significant. Miglitol alone administered at breakfast increased the AUC of the
      active plasma GLP-1 levels after lunch in sitagliptin-treated patients with
      diabetes. Our results suggest that the once-daily administration of miglitol as a
      "GLP-1 enhancer" in combination with sitagliptin was effective for the treatment
      for patients with diabetes.

PMID- 21898125
TI  - Frontotemporal dementia: from Mendelian genetics towards genome wide association
      studies.
AB  - Frontotemporal lobar degeneration is the most common cause of dementia of non
      Alzheimer's type worldwide. It manifests, clinically, with behavioural changes
      and language impairment and is pathologically associated with tau- or ubiquitin
      positive inclusions detected in neurons and glial cells of the frontal and
      temporal lobes in the brain. Genetic variations in the microtubule-associated
      protein tau and progranulin genes explain almost 50% of familial cases, whilst
      variations in TAR DNA-binding protein, charged multivescicular body protein 2B,
      valosin-containing protein and fused in sarcoma genes contribute to <5% of cases.
      The rapidly developing investigative techniques available to geneticists such as
      genome-wide association studies, whole-exome sequencing and, soon, whole-genome
      sequencing promise to contribute to the unravelling of the genetic architecture
      of this complex disease and, in the future, to the development of more sensitive,
      accurate and effective diagnostic and treatment measures.

PMID- 21898129
TI  - Regioselectivity-reversal in acylation of 6-azauridine catalyzed by Burkholderia
      cepacia lipase.
AB  - 3'-O-stearoylation of 6-azauridine was achieved enzymatically for the first time.
      Among eight commercially available lipases, that from Burkholderia cepacia
      displayed a 3'-regioselectivity of 80% towards the acylation of 3-hydroxyl of 6
      azauridine. Using an immobilized lipase from Burkholderia cepacia, the 3'
      regioselectivities of the acylations could be reversed by lengthening the
      aliphatic chain of the acyl donors (C2-C18). The possible reason might be the
      presence of the interaction between the base moiety and the acyl group.

PMID- 21898128
TI  - Isolation, characterization and docking studies of 2,3-dihydroxybiphenyl 1,2
      dioxygenase from an activated sludge metagenome.
AB  - A 2,3-dihydroxybiphenyl-1,2-dioxygenase gene (designated as bphC_meta) was
      identified in activated sludge metagenome by PCR. This gene shared 99% sequence
      identity with BphC from Burkholderia xenovorans LB400. The enzyme was purified
      from recombinant Escherichia coli with a subunit molecular mass of 32 +/- 1 kDa.
      It was optimally active at pH 9.0 and 40 degrees C, using 2,3-dihydroxybiphenyl
      as a substrate. Activity toward substituted catechols was: 2,3-dihydroxybiphenyl
      > 3-methylcatechol > catechol > 4-chlorocatechol (4-methylcatechol). The
      prediction made by molecular docking was consistent with the kinetic experimental
      data, and further explained the substrate preference of BphC_meta. The present
      study could pave the way for the improved understanding and application of BphCs
      derived from metagenomes.

PMID- 21898130
TI  - Cell recycling during repeated very high gravity bio-ethanol fermentations using
      the industrial Saccharomyces cerevisiae strain PE-2.
AB  - A very high gravity (VHG) repeated-batch fermentation system using an industrial
      strain of Saccharomyces cerevisiae PE-2 (isolated from sugarcane-to-ethanol
      distillery in Brazil) and mimicking industrially relevant conditions (high
      inoculation rates and low O(2) availability) was successfully operated during
      fifteen consecutive fermentation cycles, attaining ethanol at 17.1 +/- 0.2% (v/v)
      with a batch productivity of 3.5 +/- 0.04 g l(-1) h(-1). Moreover, this
      innovative operational strategy (biomass refreshing step) prevented critical
      decreases on yeast viability levels and promoted high accumulation of
      intracellular glycerol and trehalose, which can provide an adaptive advantage to
      yeast cells under harsh industrial environments. This study contributes to the
      improvement of VHG fermentation processes by exploring an innovative operational
      strategy that allows attaining very high ethanol titres without a critical
      decrease of the viability level thus minimizing the production costs due to
      energy savings during the distillation process.

PMID- 21898131
TI  - Cholesterol assimilation and biotransformation by Lactobacillus helveticus.
AB  - Lactobacillus helveticus, grown at 37 degrees C in MRS medium supplemented with 3
      mM cholesterol, assimilated all the cholesterol in 42 h having 68 U mg(-1) of
      intracellular cholesterol oxidase activity. The strain transformed 1 g
      cholesterol to 0.05 g of androsta-1, 4-diene-3, 17-dione and 0.04 g of androst-4
      ene-3, 17 dione within 48 h at 37 degrees C with extracellular cholesterol
      oxidase activity at 12 U mg(-1) and intracellular oxidase at 0.5 U mg(-1).

PMID- 21898132
TI  - H2 production from CO, formate or starch using the hyperthermophilic archaeon,
      Thermococcus onnurineus.
AB  - The hyperthermophilic archaeon, Thermococcus onnurineus, was grown in media
      supplemented with either CO, formate, or starch. H(2) was produced with each
      substrate with respective maximum rates of 1.55, 3.83 and 2.66 mmol H(2)/l h. The
      yields (mol H(2)/mol substrate) were 0.98, 1 and 3.13, respectively. This microbe
      is the first example where a single microorganism can grow and produce H(2) using
      CO, formate or starch as substrate.

PMID- 21898133
TI  - Solalyratins A and B, new anti-inflammatory metabolites from Solanum lyratum.
AB  - A new coumestan (solalyratin A, 1) and a novel cyclic eight-membered alpha,beta
      unsaturated ketone (solalyratin B, 3), together with three known compounds,
      puerariafuran (2), coumestrol (4) and 9-hydroxy-2',2'-dimethylpyrano[5',6':2,3]
      coumestan (5), were isolated from the whole plant of Solanum lyratum. Their
      structures were elucidated on the basis of spectroscopic analyses. In vitro,
      compounds 1-5 showed anti-inflammatory activities, with IC(50) values in the
      range 6.3-9.1 MUM.

PMID- 21898134
TI  - Accuracy of the Hospital Anxiety and Depression Scale as a screening tool in
      cancer patients: a systematic review and meta-analysis.
AB  - PURPOSE: The Hospital Anxiety and Depression Scale (HADS) is the most extensively
      validated scale for screening emotional distress in cancer patients. However,
      thresholds for clinical decision making vary widely across studies. A meta
      analysis was conducted with the aim of identifying optimal, empirically derived
      cut-offs. METHODS: PubMed, Embase, and PsycINFO databases were searched for
      studies that compared the HADS total and its subscale scores against a semi
      structured or structured clinical interview as a reference standard with regard
      to its screening efficacy for any mental disorders and depressive disorders
      alone. Separate pooled analyses were conducted for single or two adjacent
      thresholds. A total of 28 studies (inter-rater agreement, kappa = 0.86) were
      included. RESULTS: The best thresholds for screening for mental disorders were 10
      or 11 on the HADS total (sensitivity 0.80; specificity 0.74), 5 on the HADS
      depression subscale (sensitivity 0.84; specificity 0.50), and 7 or 8 on the HADS
      anxiety subscale (sensitivity 0.73; specificity 0.65). Respective thresholds for
      depression screening were 15 for the HADS total (sensitivity 0.87; specificity
      0.88), 7 for the HADS depression subscale (sensitivity 0.86; specificity 0.81),
      and 10 or 11 for the HADS anxiety subscale (sensitivity 0.63; specificity 0.83).
      CONCLUSIONS: The HADS anxiety subscale performed worse than the total and the
      depression subscales for both indicators. Diagnostic accuracy varied widely by
      threshold but was consistently superior for depression screening than for
      screening of any mental disorder.

PMID- 21898135
TI  - Correction of susceptibility-induced GRE phase shift for accurate PRFS
      thermometry proximal to cryoablation iceball.
AB  - INTRODUCTION: The susceptibility contrast between frozen and unfrozen tissue
      disturbs the local magnetic field in the proximity of the ice-ball during
      cryotherapy. This effect should be corrected for in real time to allow PRFS-based
      monitoring of near-zero temperatures during intervention. MATERIAL AND METHODS:
      Susceptibility artifacts were corrected post-processing, using a rapid numerical
      algorithm. The difference in bulk magnetic susceptibility between frozen and non
      frozen tissue was approximated to be uniform over the ice-ball volume and was
      determined from the isothermal principle applied to the phase-transition frontier
      of compartments. Subsequently, the magnetic perturbation field was calculated
      rapidly in 3D using a Fourier-convolution. Experimental studies were performed
      for two scenarios: tissue defrosting in a water bath and induction of an ice-ball
      by a MR-compatible cryogenic probe. RESULTS: The susceptibility artifacts yielded
      PRFS temperature errors as high as 10-12 degrees C proximal to the ice-ball,
      positive or negative depending on the relative orientation of the position vector
      from the B(o) direction. These effects were fully corrected for to within the
      noise range. The susceptibility-corrected PRFS temperature values were consistent
      with the phase-transition isothermal condition, irrespective of the local
      orientation of the position vector. CONCLUSION: By implementing on-line the post
      processing algorithm, PRFS MRT may be used as a safety tool for non-invasive and
      accurate monitoring of near-zero temperatures during MR-guided clinical
      cryotherapy.

PMID- 21898136
TI  - Anti-NMDA receptor antibodies in a case of MELAS syndrome.

PMID- 21898137
TI  - Levetiracetam versus lorazepam in status epilepticus: a randomized, open labeled
      pilot study.
AB  - For the management of status epilepticus (SE), lorazepam (LOR) is recommended as
      the first and phenytoin or fosphenytoin as the second choice. Both these drugs
      have significant toxicity. Intravenous levetiracetam (LEV) has become available,
      but its efficacy and safety has not been reported in comparison to LOR. We report
      a randomized, open labeled pilot study comparing the efficacy and safety of LEV
      and LOR in SE. Consecutive patients with convulsive or subtle convulsive SE were
      randomized to LEV 20 mg/kg IV over 15 min or LOR 0.1 mg/kg over 2-4 min. Failure
      to control SE within 10 min of administration of one study drug was treated by
      the other study drug. The primary endpoint was clinical seizure cessation and
      secondary endpoints were 24 h freedom from seizure, hospital mortality, and
      adverse events. Our results are based on 79 patients. Both LEV and LOR were
      equally effective. In the first instance, the SE was controlled by LEV in 76.3%
      (29/38) and by LOR in 75.6% (31/41) of patients. In those resistant to the above
      regimen, LEV controlled SE in 70.0% (7/10) and LOR in 88.9% (8/9) patients. The
      24-h freedom from seizure was also comparable: by LEV in 79.3% (23/29) and LOR in
      67.7% (21/31). LOR was associated with significantly higher need of artificial
      ventilation and insignificantly higher frequency of hypotension. For the
      treatment of SE, LEV is an alternative to LOR and may be preferred in patients
      with respiratory compromise and hypotension.

PMID- 21898138
TI  - Patterns of dietary and herbal supplement use by multiple sclerosis patients.
AB  - To assess the patterns of dietary (DS) and herbal supplement (HS) use in MS
      patients, compare use between MS patients and healthy controls and to identify
      potential interactions with drugs used to treat MS. This study included 279 MS
      subjects and 161 controls from a study of risk factors in MS. All patients
      received a neurological examination. All subjects provided responses to a
      standardized questionnaire administered during an in-person interview. A larger
      proportion of MS patients (82.1%) compared to controls (60.1%) used one or more
      DS regularly for at least 3 months (p < 0.001). There was a trend toward a higher
      proportion of MS patients (26.6%) versus controls (17.8%) who used HSs for more
      than 1 month (p = 0.038). The most common DS used after MS onset was a
      multivitamin (78.1%), followed by vitamin D (65.8%). Use of the majority of
      specific DSs increased significantly after MS onset compared to before. The
      proportion of controls and MS patients after MS onset who reported using an
      individual HS was generally similar. The most commonly used HS in patients after
      MS was evening primrose oil (40.4%) followed by cranberry fruit extract (35.2%).
      There was no evidence for associations with progressive disease course or with
      choice of disease-modifying treatment. Dietary supplements are used more
      frequently by MS patients than controls. Use tends to increase after MS onset
      compared to before, especially for DS. The use of HS by MS patients is only
      modestly greater than by controls.

PMID- 21898139
TI  - Cerebrospinal fluid findings in adults with acute Lyme neuroborreliosis.
AB  - Presence of BB-specific antibodies in the cerebrospinal fluid (CSF) with evidence
      of their intrathecal production in conjunction with the white cell count in the
      CSF and typical clinical symptoms is the traditional diagnostic gold standard of
      Lyme neuroborreliosis (LNB). Few data are available on the CSF lactate
      concentration in European adults with the diagnosis of acute LNB. The objective
      of the study was to investigate the CSF changes during acute LNB. Routine CSF
      parameters [leukocyte count, protein, lactate and albumin concentrations,
      CSF/serum quotients of albumin (Q(Alb)), IgG, IgA and IgM, and oligoclonal IgG
      bands] and the Borrelia burgdorferi (BB)-specific antibody index were
      retrospectively studied in relation to the clinical presentation in patients
      diagnosed with acute LNB. A total of 118 patients with LNB were categorized into
      the following groups according to their symptoms at presentation; group 1:
      polyradiculoneuritis (Bannwarth's syndrome), group 2: isolated facial palsy and
      group 3: predominantly meningitic course of the disease. In addition to the CSF
      of patients with acute LNB, CSF of 19 patients with viral meningitis (VM) and 3
      with neurolues (NL) were analyzed. There were 97 patients classified with
      definite LNB, and 21 as probable LNB. Neck stiffness and fever were reported by
      15.3% of patients. Most of these patients were younger than 50 years.
      Polyradiculoneuritis was frequently found in patients older than 50 years.
      Lymphopleocytosis was found in all patients. Only 5 patients had a CSF lactate
      >=3.5 mmol/l, and the mean CSF lactate level was not elevated (2.1 +/- 0.6
      mmol/l). The patients with definite LNB had significantly higher lactate levels
      than patients with probable LNB. Elevated lactate levels were accompanied by
      fever and headache. In the Reiber nomograms, intrathecal immunoglobulin synthesis
      was found for IgM in 70.2% followed by IgG in 19.5%. Isoelectric focussing
      detected an intrathecal IgG synthesis in 83 patients (70.3%). Elevated BB AIs in
      the CSF were found in 97 patients (82.2%). Patients with VM showed lower CSF
      protein concentration and CSF/serum quotients of albumin than LNB patients. In
      acute LNB, all patients had elevated cerebrospinal fluid (CSF) leukocyte counts.
      In contrast to infections by other bacteria, CSF lactate was lower than 3.5
      mmol/l in all but 5 patients. The CSF findings did not differ between
      polyradiculoneuritis, facial palsy, and meningitis. The CSF in LNB patients
      strongly differed from CSF in VM patients with respect to protein concentration
      and the CSF/serum albumin quotient.

PMID- 21898140
TI  - Evaluation of false positive rate based on exposure-response analyses for two
      compounds in fixed-dose combination products.
AB  - We explored the type I error rate (false positive rate) associated with exposure
      response (ER) analyses for two compounds in a fixed-dose combination product
      through simulations. In the simulations, at least one compound was assumed to be
      inactive, whereas the active compound followed E(max) model at different
      concentration ranges. The simulated data were independently evaluated by pre
      specified univariate or multivariate linear, log-linear models, and mixed linear
      log-linear models. The type I error rate was evaluated by comparing the total
      number of falsely identified significant slope estimates with the total number of
      models with successful convergence. We demonstrated that ER analyses results
      based on data from fixed-dose combination products at various dose levels should
      be interpreted with caution. A univariate analysis, even though is appropriate to
      guide dose selection, is inadequate to identify the active compound. Multivariate
      analyses can be applied to determine the active compound only when the underlying
      ER relationship for each compound (especially for the active compound) has been
      adequately defined or approximated. The false positive rate in determining a
      significant ER relationship is elevated, when the underlying ER relationship
      (especially for the active compound) is erroneously or inadequately defined.
      Without the assurance of the correct structural models, the identified
      significant ER relationship does not necessarily indicate that the compound
      associated with the significant slope estimate is pharmacologically active.

PMID- 21898141
TI  - IL-9 contributes to immunosuppression mediated by regulatory T cells and mast
      cells in B-cell non-hodgkin's lymphoma.
AB  - It has been known that regulatory T (Treg) cells and mast cells (MCs) are
      involved in tumor immunity regulation, but the exact roles and mechanisms of Treg
      cells and MCs in B-cell non-Hodgkin's lymphoma (NHL) are incompletely defined. In
      the present study, we found that the number of Foxp3(+) Treg cells and CD117(+)
      MCs increased in B-cell NHL patients. Concomitantly, a high level of interleukin
      (IL)-9 was observed in the sera from B-cell NHL patients. Neutralizing IL-9
      significantly inhibited tumor growth in the lymphoma model of murine, and this
      process was associated with down-regulation of Treg cells and MCs. Furthermore,
      IL-9 was also demonstrated to induce expression of MC-related genes and
      proliferation of MCs from the bone marrow stem cells. Collectively, our results
      indicate that Treg cell and MCs are involved in immunosuppression in B-cell NHL,
      and IL-9 is a key mediator of Treg cells and MCs in that process. These findings
      provide novel insight for the pathogenesis and possible therapeutic strategy of B
      cell NHL.

PMID- 21898144
TI  - Strength and hypertrophy with resistance training: chasing a hormonal ghost.

PMID- 21898142
TI  - Association of IRF5 polymorphisms with susceptibility to hemophagocytic
      lymphohistiocytosis in children.
AB  - INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory
      syndrome and has a varied genetic background. The polymorphism of interferon
      regulatory factor 5 gene (IRF5) was reported to be associated with susceptibility
      to macrophage activation syndrome. IRF5 acts as a master transcription factor in
      the activation of pro-inflammatory cytokines. We assessed associations of IRF5
      gene polymorphisms with susceptibility to secondary HLH. METHODS: Three IRF5
      single nucleotide polymorphisms (rs729302, rs2004640, and rs2280714) were
      genotyped using TaqMan assays in 82 secondary HLH patients and 188 control
      subjects. RESULTS: There was a significant association of the GT/TT genotype at
      rs2004640 with secondary HLH susceptibility (p < 0.01). The IRF5 haplotype
      (rs729302 A, rs2004640 T, and rs2280714 T) was associated with secondary HLH
      susceptibility (p < 0.01). CONCLUSIONS: These findings indicate that IRF5 is a
      genetic factor influencing the susceptibility to secondary HLH and that the IRF5
      associated immune response contributes to the pathogenesis of HLH.

PMID- 21898145
TI  - Skeletal muscle reoxygenation after high-intensity exercise in mitochondrial
      myopathy.
AB  - This study addressed whether O(2) delivery during recovery from high-intensity,
      supra-gas exchange threshold exercise would be matched to O(2) utilization at the
      microvascular level in patients with mitochondrial myopathy (MM). Off-exercise
      kinetics of (1) pulmonary O(2) uptake VO(2P) (2) an index of fractional O(2)
      extraction by near-infrared spectroscopy (Delta[deoxy-Hb + Mb]) in the vastus
      lateralis and (3) cardiac output (Q'(T)) by impedance cardiography were assessed
      in 12 patients with biopsy-proven MM (chronic progressive external
      ophthalmoplegia) and 12 age- and gender-matched controls. Kinetics of VO(2P) were
      significantly slower in patients than controls (tau = 53.8 +/- 16.5 vs. 38.8 +/-
      7.6 s, respectively; p < 0.05). Q'(T), however, declined at similar rates (tau =
      64.7 +/- 18.8 vs. 73.0 +/- 21.6 s; p > 0.05) being typically slower than
      [Formula: see text] in both groups. Importantly, Delta[deoxy-Hb + Mb] dynamics
      (MRT) were equal to, or faster than, tauVO(2P) in patients and controls,
      respectively. In fact, there were no between-group differences in
      tauVO(2P)MRTDelta[deoxy-Hb + Mb] (1.1 +/- 0.4 vs. 1.0 +/- 0.2, p > 0.05) thereby
      indicating similar rates of microvascular O(2) delivery. These data indicate that
      the slower rate of recovery of muscle metabolism after high-intensity exercise is
      not related to impaired microvascular O(2) delivery in patients with MM. This
      phenomenon, therefore, seems to reflect the intra-myocyte abnormalities that
      characterize this patient population.

PMID- 21898147
TI  - Constructing productive engagement: pre-engagement tools for emerging
      technologies.
AB  - Engagement with stakeholders and civil society is increasingly important for new
      scientific and technological developments. Preparation of such engagements sets
      the stage for engagement activities and thus contributes to their outcomes.
      Preparation is a demanding task, particularly if the facilitating agent aims for
      timely engagement related to emerging technologies. Requirements for such
      preparation include understanding of the emerging science & technology and its
      dynamics. Multi-level analysis and socio-technical scenarios are two
      complementary tools for constructing productive engagement. Examination of the
      emergence of nanotechnologies in the food packaging sector demonstrates how these
      tools work. In light of recent policy demands for responsible innovation, but
      also more generally, the role of organizers of engagement activities is one that
      deserves reflection insofar as it can extend beyond that of preparation and
      facilitation.

PMID- 21898146
TI  - Unravelling secretion in Cryptococcus neoformans: more than one way to skin a
      cat.
AB  - Secretion pathways in fungi are essential for the maintenance of cell wall
      architecture and for the export of a number of virulence factors. In the fungal
      pathogen, Cryptococcus neoformans, much evidence supports the existence of more
      than one route taken by secreted molecules to reach the cell periphery and
      extracellular space, and a significant degree of crosstalk between conventional
      and non-conventional secretion routes. The need for such complexity may be due to
      differences in the nature of the exported cargo, the spatial and temporal
      requirements for constitutive and non-constitutive protein secretion, and/or as a
      means of compensating for the extra burden on the secretion machinery imposed by
      the elaboration of the polysaccharide capsule. This review focuses on the role of
      specific components of the C. neoformans secretion machinery in protein and/or
      polysaccharide export, including Sec4, Sec6, Sec14, Golgi reassembly and stacking
      protein and extracellular exosome-like vesicles. We also address what is known
      about traffic of the lipid, glucosylceramide, a target of therapeutic antibodies
      and an important regulator of C. neoformans pathogenicity, and the role of
      signalling pathways in the regulation of secretion.

PMID- 21898148
TI  - Associations between hurtful weight-related comments by family and significant
      other and the development of disordered eating behaviors in young adults.
AB  - Research has found that weight-teasing is associated with disordered eating in
      adolescents. This study expands on the existing research by examining
      associations between hurtful weight comments by family and a significant other
      and disordered eating in young adults. Data come from 1,902 young adults (mean
      age 25) who completed surveys in 1998, 2003 and 2009. Correlations were examined
      between receiving hurtful comments from family and significant others, and four
      disordered eating behaviors in young adulthood, adjusting for prior disordered
      eating and prior teasing. Disordered eating behaviors were common in young
      adulthood, and were associated with hearing hurtful weight-related comments from
      family members and a significant other, for both females and males. Disordered
      eating prevention activities, which include messages about the potential harm
      associated with hurtful weight-related comments, should be expanded to address
      young adults, and programs may want to target relationship partners.

PMID- 21898149
TI  - Cellulase production from agricultural residues by recombinant fusant strain of a
      fungal endophyte of the marine sponge Latrunculia corticata for production of
      ethanol.
AB  - Several fungal endophytes of the Egyptian marine sponge Latrunculia corticata
      were isolated, including strains Trichoderma sp. Merv6, Penicillium sp. Merv2 and
      Aspergillus sp. Merv70. These fungi exhibited high cellulase activity using
      different lignocellulosic substrates in solid state fermentations (SSF). By
      applying mutagenesis and intergeneric protoplast fusion, we have obtained a
      recombinant strain (Tahrir-25) that overproduced cellulases (exo-beta-1,4
      glucanase, endo-beta-1,4-glucanase and beta-1,4-glucosidase) that facilitated
      complete cellulolysis of agricultural residues. The process parameters for
      cellulase production by strain Tahrir-25 were optimized in SSF. The highest
      cellulase recovery from fermentation slurries was achieved with 0.2% Tween 80 as
      leaching agent. Enzyme production was optimized under the following conditions:
      initial moisture content of 60% (v/w), inoculum size of 10(6) spores ml(-1),
      average substrate particle size of 1.0 mm, mixture of sugarcane bagasse and
      corncob (2:1) as the carbon source supplemented with carboxymethyl cellulose
      (CMC) and corn steep solids, fermentation time of 7 days, medium pH of 5.5 at 30
      degrees C. These optimized conditions yielded 450, 191, and 225 units/gram dry
      substrate (U gds(-1)) of carboxylmethyl cellulase, filter-paperase (FPase), and
      beta-glucosidase, respectively. Subsequent fermentation by the yeast,
      Saccharomyces cerevisiae NRC2, using lignocellulose hydrolysates obtained from
      the optimized cellulase process produced the highest amount of ethanol (58 g l(
      1)). This study has revealed the potential of exploiting marine fungi for cost
      effective production of cellulases for second generation bioethanol processes.

PMID- 21898150
TI  - Fusarium proliferatum, an endophytic fungus from Dysoxylum binectariferum Hook.f,
      produces rohitukine, a chromane alkaloid possessing anti-cancer activity.
AB  - Rohitukine is a chromane alkaloid possessing anti-inflammatory, anti-cancer and
      immuno-modulatory properties. The compound was first reported from Amoora
      rohituka (Meliaceae) and later from Dysoxylum binectariferum (Meliaceae) and
      Schumanniophyton problematicum (Rubiaceae). Flavopiridol, a semi-synthetic
      derivative of rohitukine is a potent CDK inhibitor and is currently in Phase III
      clinical trials. In this study, the isolation of an endophytic fungus, Fusarium
      proliferatum (MTCC 9690) from the inner bark tissue of Dysoxylum binectariferum
      Hook.f (Meliaceae) is reported. The endophytic fungus produces rohitukine when
      cultured in shake flasks containing potato dextrose broth. The yield of
      rohitukine was 186 MUg/100 g dry mycelial weight, substantially lower than that
      produced by the host tissue. The compound from the fungus was authenticated by
      comparing the LC-HRMS and LC-HRMS/MS spectra with those of the reference standard
      and that produced by the host plant. Methanolic extract of the fungus was
      cytotoxic against HCT-116 and MCF-7 human cancer cell lines (IC(50) = 10 MUg/ml
      for both cancer cell lines).

PMID- 21898153
TI  - MRI contrast enhancement of malignant liver tumours following successful
      cryoablation.
AB  - OBJECTIVES: To assess the incidence and degree of MRI contrast enhancement in
      liver tumours following successful percutaneous cryoablation. METHODS: Thirty
      eight patients with liver metastases (n = 29) or hepatocellular carcinoma (n = 9)
      underwent percutaneous cryoablation of 45 tumours between March 2004 and June
      2009, with complete ablation zone coverage of the tumour and no local recurrence
      on follow-up imaging to date (range 3-60 months, mean 16). Contrast-enhanced MRI
      was used to assess 45 tumours at 24 h, 32 tumours at 2-4 months, and 21 tumours
      at 5-7 months. Percentage of tumours with contrast enhancement was assessed using
      dynamic spoiled gradient echo T1-weighted images. RESULTS: Twenty-four hours post
      cryoablation, 23 out of 45 tumours (51%) enhanced compared with 42 out of 43
      (98%) pre-ablation (p < 0.001). Mean percentage tumour enhancement decreased from
      157% (range 26-745%) pre-ablation, to 107% (27-260%) at 24 h (p = 0.003), and 43%
      (24-103%) at 2-4 months (p < 0.001). The incidence and degree of tumour
      enhancement decreased through 5-7 months. CONCLUSIONS: Unlike previously reported
      studies of radiofrequency ablation, successful cryoablation of liver tumours is
      often associated with persistent tumour contrast enhancement on MRI performed at
      24 h and decreasing over 2-7 months. KEY POINTS: * Liver neoplasms often
      demonstrate MRI contrast enhancement following successful percutaneous
      cryoablation. * This differs from radiofrequency ablation techniques where
      contrast enhancement suggests residual tumour * This difference could potentially
      lead to important errors in follow up strategies.

PMID- 21898151
TI  - Non-cancer endpoints in BRCA1/2 carriers after risk-reducing salpingo
      oophorectomy.
AB  - Risk-reducing salpingo-oophorectomy (RRSO) significantly reduces the risk of
      ovarian cancer and breast cancer in pre-menopausal women with BRCA1 and BRCA2
      (B1/2) mutations. Despite its clear benefits, little is known about non-cancer
      endpoints in this population. Medical records were examined in 226 B1/2 mutation
      carriers, who had previously undergone RRSO with a focus on bone health as well
      as the frequency of hypertension, hyperlipidemia, coronary artery disease (CAD),
      myocardial infarction (MI), diabetes, hypothyroidism and depression. From the
      medical records, DEXA scans, medications and medical conditions were recorded. Of
      the 226 patient records examined, 16% (36/226) had hypertension, 17% (39/226)
      hyperlipidemia, 2% (5/226) CAD or MI, 2% (4/226) diabetes, 13% (29/226)
      hypothyroidism and 14% (31/226) depression. DEXA results were available in 152
      women. Of those DEXA scans, 71% (108/152) were abnormal (57% osteopenia and 14%
      osteoporosis). Among women who underwent RRSO prior to age 50, 71% (62/88) had
      osteopenia/osteoporosis. Although there was no difference in
      osteopenia/osteoporosis in women with RRSO prior to age 50 compared to those RRSO
      > 50, the age at follow up in these two groups differs greatly (mean age 44.7 vs.
      60.6), suggesting that both current age and age at RRSO contribute to bone health
      assessment. In summary, here, we report the prevalence of non-cancer endpoints in
      a cohort of B1/2 mutation carriers and note a particularly high rate of
      osteopenia and osteoporosis in B1/2 with breast cancer undergoing RRSO prior to
      50. Despite the risk reduction RRSO offers, attention should be paid to non
      cancer endpoints, particularly bone health, in this population.

PMID- 21898154
TI  - An IUPAC-based approach to estimate the detection limit in co-extraction-based
      optical sensors for anions with sigmoidal response calibration curves.
AB  - An approach based on IUPAC methodology to estimate the limit of detection of bulk
      optode-based analytical methods for anions has been developed. The traditional
      IUPAC methodology for calculating the detection limit was modified to be adapted
      to particular cases where the calibration curves have a sigmoidal profile.
      Starting from the different full theoretical models for every co-extraction
      mechanism of the analyte in the membrane in bulk optodes, several particular
      simplified models at low analyte concentration were obtained and validated. The
      slope of the calibration curve at low analyte concentration was calculated from
      the first derivative of the simplified equation and, subsequently, the detection
      limit was estimated. This fitted-for-purpose estimation strategy was applied to
      anion quantification for in-house bulk optode-based analytical methods, and the
      estimated limits of detection were compared with those obtained by applying
      classical geometrical methodology. This way of establishing the detection limit
      yields values that maintain their true statistical and probabilistic aspects. It
      can be easily applied to any analytical system which yields non-linear
      calibration curves at low analyte concentration.

PMID- 21898152
TI  - Regulation of immune cell function and differentiation by the NKG2D receptor.
AB  - NKG2D is one of the most intensively studied immune receptors of the past decade.
      Its unique binding and signaling properties, expression pattern, and functions
      have been attracting much interest within the field due to its potent antiviral
      and anti-tumor properties. As an activating receptor, NKG2D is expressed on cells
      of the innate and adaptive immune system. It recognizes stress-induced MHC class
      I-like ligands and acts as a molecular sensor for cells jeopardized by viral
      infections or DNA damage. Although the activating functions of NKG2D have been
      well documented, recent analysis of NKG2D-deficient mice suggests that this
      receptor may have a regulatory role during NK cell development. In this review,
      we will revisit known aspects of NKG2D functions and present new insights in the
      proposed influence of this molecule on hematopoietic differentiation.

PMID- 21898155
TI  - AFM imaging of ALYGNSA polymer-protein surfaces: evidence of antibody
      orientation.
AB  - Previous investigations found the combination of recombinant bacterial protein G
      (rProG) and poly(methyl methacrylate) (PMMA) to produce a greater proportion of
      oriented antibodies. PMMA-rProG yielded a sixfold greater availability of
      antibody Fab regions compared with other bacterial affinity linker protein and
      polymer pairings, including commercially available polystyrene (PS) high-binding
      96-well microplates. Given the name ALYGNSA, the PMMA-rProG combination was
      developed into a fluorescence assay and evaluated in conjunction with
      commercially available cancer biomarker enzyme-linked immunosorbent assays
      (ELISAs). In each study, a lower limit of detection was seen with the ALYGNSA
      assay. The purpose of this investigation was to examine the ALYGNSA substrate in
      contrast with a commonly used ELISA substrate and analyze the affinity
      immobilized antibodies for additional evidence of orientation. Non-contact atomic
      force microscopy is a logical method as it operates in ambient conditions, can be
      used directly on biological samples without modification, and offers the
      resolution necessary to identify the position of the antibody on the surface.
      Dynamic contact angle studies were employed to examine untreated PMMA and PS
      samples and revealed important differences in their surface characters.
      Comparative height threshold grain analysis of the prepared ALYGNSA surface, a
      similarly treated mica surface, and a gold colloid sizing standard evaluated and
      confirmed the antibody orientation of the ALYGNSA system.

PMID- 21898157
TI  - High-throughput mass finger printing and Lewis blood group assignment of human
      milk oligosaccharides.
AB  - The structural diversity of human milk oligosaccharides (HMOs) strongly depends
      on the Lewis (Le) blood group status of the donor which allows a classification
      of these glycans into three different groups. Starting from 50 MUL of human milk,
      a new high-throughput, standardized, and widely automated mass spectrometric
      approach has been established which can be used for correlation of HMO structures
      with the respective Lewis blood groups on the basis of mass profiles of the
      entire mixture of glycans together with selected fragment ion spectra. For this
      purpose, the relative abundance of diagnostically relevant compositional species,
      such as Hex(2)Fuc(2) and Hex(3)HexNAc(1)Fuc(2), as well as the relative
      intensities of characteristic fragment ions obtained thereof are of key
      importance. For each Lewis blood group, i.e., Le(a-b+), Le(a+b-), and Le(a-b-),
      specific mass profile and fragment ion patterns could be thus verified. The
      described statistically proven classification of the derived glycan patterns may
      be a valuable tool for analysis and comparison of large sets of milk samples in
      metabolic studies. Furthermore, the outlined protocol may be used for rapid
      screening in clinical studies and quality control of milk samples donated to milk
      banks.

PMID- 21898156
TI  - Solution-phase detection of dual microRNA biomarkers in serum.
AB  - A strategy for the simultaneous detection of multiple microRNA (miRNA) targets
      was developed utilizing fluorophore/quencher-labeled oligonucleotide probe sets.
      Two miRNA targets (miR-155 and miR-103), whose misregulation has afforded them
      status as putative biomarkers in certain types of cancer, were detected using our
      assay design. In the absence of target, the complementary fluorophore-probe and
      quencher-probe hybridize, resulting in a fluorescence resonance energy transfer
      based quenching of the fluorescence signal. In the presence of unlabeled target,
      however, the antisense quencher-probe can hybridize with the target, resulting in
      increased fluorescence intensity as the quencher-probe is sequestered beyond the
      Forster radius of the fluorescent-probe. The assay design was tested in multiple
      matrices of buffer, cellular extract, and serum; and detection limits were found
      to be matrix-dependent, ranging from 0.34 to 8.89 pmol (3.4-59.3 nM) for miR-155
      and 2.90-11.8 pmol (19.3-79.0 nM) for miR-103. Single, double, and triple
      nucleotide selectivity was also tested. Additionally, miR-155 concentrations were
      assessed in serum samples obtained directly from breast cancer patients without
      the need for RNA extraction. This assay is quantitative, possesses a low
      detection limit, can be applied in multiple complex matrices, and can obtain
      single-nucleotide selectivity. This method can be employed for the multiplex
      detection of solution-phase DNA or RNA targets and, more specifically, for the
      direct detection of serum miRNA biomarkers.

PMID- 21898158
TI  - GazeAlyze: a MATLAB toolbox for the analysis of eye movement data.
AB  - This article presents GazeAlyze, a software package, written as a MATLAB
      (MathWorks Inc., Natick, MA) toolbox developed for the analysis of eye movement
      data. GazeAlyze was developed for the batch processing of multiple data files and
      was designed as a framework with extendable modules. GazeAlyze encompasses the
      main functions of the entire processing queue of eye movement data to static
      visual stimuli. This includes detecting and filtering artifacts, detecting
      events, generating regions of interest, generating spread sheets for further
      statistical analysis, and providing methods for the visualization of results,
      such as path plots and fixation heat maps. All functions can be controlled
      through graphical user interfaces. GazeAlyze includes functions for correcting
      eye movement data for the displacement of the head relative to the camera after
      calibration in fixed head mounts. The preprocessing and event detection methods
      in GazeAlyze are based on the software ILAB 3.6.8 Gitelman (Behav Res Methods
      Instrum Comput 34(4), 605-612, 2002). GazeAlyze is distributed free of charge
      under the terms of the GNU public license and allows code modifications to be
      made so that the program's performance can be adjusted according to a user's
      scientific requirements.

PMID- 21898159
TI  - Introducing LexTALE: a quick and valid Lexical Test for Advanced Learners of
      English.
AB  - The increasing number of experimental studies on second language (L2) processing,
      frequently with English as the L2, calls for a practical and valid measure of
      English vocabulary knowledge and proficiency. In a large-scale study with Dutch
      and Korean speakers of L2 English, we tested whether LexTALE, a 5-min vocabulary
      test, is a valid predictor of English vocabulary knowledge and, possibly, even of
      general English proficiency. Furthermore, the validity of LexTALE was compared
      with that of self-ratings of proficiency, a measure frequently used by L2
      researchers. The results showed the following in both speaker groups: (1) LexTALE
      was a good predictor of English vocabulary knowledge; 2) it also correlated
      substantially with a measure of general English proficiency; and 3) LexTALE was
      generally superior to self-ratings in its predictions. LexTALE, but not self
      ratings, also correlated highly with previous experimental data on two word
      recognition paradigms. The test can be carried out on or downloaded from
      www.lextale.com .

PMID- 21898160
TI  - Optimization of Toxoplasma gondii DNA extraction from amniotic fluid using
      NucliSENS easyMAG and comparison with QIAamp DNA minikit.
AB  - Antenatal diagnosis of congenital toxoplasmosis relies on PCR in amniotic fluid.
      Because parasitic load is often low, DNA extraction must be optimized. Manual
      methods remain widespread although automated methods appear more effective. This
      study aimed at optimizing an automated method and at comparing it with a
      widespread manual method: QIAamp DNA minikit. To optimize NucliSens easyMAG, we
      evaluated the addition of proteinase K pre-treatment and the increase of the
      amount of silica particles used for the extraction. The optimized method was then
      compared to QIAamp DNA minikit on samples containing less than 25 tachyzoites/ml.
      NucliSens easyMAG DNA yield was improved after proteinase K pre-treatment (p <
      0.01), but not with a higher silica particle input. The optimized method yielded
      more positive PCRs than the manual method, especially for samples containing 5
      tachyzoites/ml or less (71% vs 26%, p < 10(-4)). The DNA amount in samples found
      positive by PCR was higher after optimized automated extraction than after manual
      extraction (p < 10(-4)). Proteinase K pre-treatment should be added to extract
      DNA from amniotic fluid using NucliSens easyMAG. Using this optimized automated
      method rather than manual methods would improve the sensitivity of Toxoplasma PCR
      and simplify the daily workflow.

PMID- 21898161
TI  - Bone substitute biomedical material of multi-(amino acid) copolymer: in vitro
      degradation and biocompatibility.
AB  - Degradable polymers with good mechanical strength as bone repair biomaterials
      have been paid more attention in biomedical application. In this study, a multi
      (amino acid) copolymer consisting of 6-aminocaproic acid and five natural amino
      acids was prepared by a reaction of acid-catalyzed condensation. The results
      revealed that the copolymer could be slowly degradable in Tris-HCl solution, and
      lost its initial weight of 31.9 wt% after immersion for 12 weeks, and the changes
      of pH value of Tris-HCl solution were in range from 6.9 to 7.4 during soaking.
      The compressive strength of the copolymer decreased from 107 to 68 MPa after
      immersion for 12 weeks. The proliferation and differentiation of MG-63 cells on
      the copolymer significantly increased with time, and the cells with normal
      phenotype extended and spread well on the copolymer surfaces. When the copolymer
      was implanted in muscle and bone defects of femoral cortex of dogs for 12 weeks,
      the histological evaluation confirmed that the copolymer exhibited excellent
      biocompatibility and more effective osteogenesis in vivo. When implanted into
      cortical bone defects of dogs, the copolymer could be combined directly with the
      natural bone without fibrous capsule tissue between implants and host bone. The
      results indicated that the multi-(amino acid) copolymer with sufficient strength,
      good biocompatibility and osteoconductivity had clinical potential for load
      bearing bone repair or substitution.

PMID- 21898162
TI  - Mixed learning algorithms and features ensemble in hepatotoxicity prediction.
AB  - Drug-induced liver injury, although infrequent, is an important safety concern
      that can lead to fatality in patients and failure in drug developments. In this
      study, we have used an ensemble of mixed learning algorithms and mixed features
      for the development of a model to predict hepatic effects. This robust method is
      based on the premise that no single learning algorithm is optimum for all
      modelling problems. An ensemble model of 617 base classifiers was built from a
      diverse set of 1,087 compounds. The ensemble model was validated internally with
      five-fold cross-validation and 25 rounds of y-randomization. In the external
      validation of 120 compounds, the ensemble model had achieved an accuracy of
      75.0%, sensitivity of 81.9% and specificity of 64.6%. The model was also able to
      identify 22 of 23 withdrawn drugs or drugs with black box warning against
      hepatotoxicity. Dronedarone which is associated with severe liver injuries,
      announced in a recent FDA drug safety communication, was predicted as hepatotoxic
      by the ensemble model. It was found that the ensemble model was capable of
      classifying positive compounds (with hepatic effects) well, but less so on
      negatives compounds when they were structurally similar. The ensemble model built
      in this study is made available for public use.

PMID- 21898163
TI  - Conformational analysis of the MUBetaRho83-99 (Phe91) and MUBetaRho83-99 (Tyr91)
      peptide analogues and study of their interactions with the HLA-DR2 and human TCR
      receptors by using molecular dynamics.
AB  - The two new synthetic analogues of the MBP(83-99) epitope substituted at Lys(91)
      (primary TCR contact) with Phe [MBP(83-99) (Phe(91))] or Tyr [MBP(83-99)
      (Tyr(91))], have been structurally elucidated using 1D and 2D high resolution NMR
      studies. The conformational analysis of the two altered peptide ligands (APLs)
      has been performed and showed that they adopt a linear and extended conformation
      which is in agreement with the structural requirements of the peptides that
      interact with the HLA-DR2 and TCR receptors. In addition, Molecular Dynamics (MD)
      simulations of the two analogues in complex with HLA-DR2 (DRA, DRB1*1501) and TCR
      were performed. Similarities and differences of the binding motif of the two
      analogues were observed which provide a possible explanation of their biological
      activity. Their differences in the binding mode in comparison with the MBP(83-99)
      epitope may also explain their antagonistic versus agonistic activity. The
      obtained results clearly indicate that substitutions in crucial amino acids (TCR
      contacts) in combination with the specific conformational characteristics of the
      MBP(83-99) immunodominant epitope lead to an alteration of their biological
      activity. These results make the rational drug design intriguing since the
      biological activity is very sensitive to the substitution and conformation of the
      mutated MBP epitopes.

PMID- 21898164
TI  - Blunt cerebrovascular injuries in acute trauma care: a screening protocol.
AB  - INTRODUCTION: Blunt cerebrovascular injuries (BCVI) of the extra- or
      intracerebral vessels are frequently observed lesions which may lead to
      thrombembolic events with focal neurological deficits, stroke or death
      particularly in patients <60 years. However, a comprehensive standardised
      clinical algorithm for screening and management of these secondary injuries is
      still lacking. MATERIALS AND METHODS: We developed a standardised screening
      protocol applicable for mild as well as severely injured patients. In this
      prospective cohort study, we evaluated the feasibility of this diagnostic
      algorithm in a level 1 trauma centre setting. Trauma patients who met the
      inclusion criteria underwent a computed tomographic angiography (CTA) as part of
      standard diagnostic procedure at admission. All suspicions or positive findings
      were reevaluated by a conventional four-vessel catheter angiography within the
      first 72 h after trauma. Within this period, anticoagulation with low-dose
      heparin was started. BCVI confirmation indicated a shift to systemic
      heparinisation with overlapping phenprocoumon therapy for at least 6 months. All
      patients were reevaluated after 6 months by another four-vessel angiography.
      Depending on the diagnostic findings, oral anticoagulation may be discontinued or
      continued for another 6 months. RESULTS: A total of 44 patients (8 male, 6
      female, age range 19-95 years) were included in the study. 20 BCVIs were detected
      in 16 patients (36.3%). The most common injuries identified were Biffl Type II
      (40%) and Type IV lesions (30%). 86.4% of the patients received a CTA upon
      admission, 93.2% of which were conducted within 12 h posttrauma. None of the
      patients had a secondary thrombembolic neurological event during the hospital
      stay or within 3 months postdischarge. CONCLUSION: Our results indicate that
      implementation of the screening protocol can prevent strokes in patients without
      primary thrombembolic neurological deficits.

PMID- 21898165
TI  - Change in Cobb angle of each segment of the major curve after posterior vertebral
      column resection (PVCR): a preliminary discussion of correction mechanisms of
      PVCR.
AB  - INTRODUCTION: Posterior vertebral column resection (PVCR) is an effective
      technique for treating severe rigid spinal deformities, and no other osteotomy is
      capable for such an excellent corrective effects. The purpose of this study was
      to discuss the correction mechanisms of PVCR. MATERIALS AND METHODS: Forty-six
      patients with severe rigid spinal deformities undergoing PVCR were
      retrospectively analyzed. According to a routine posteroanterior supine entire
      spine radiograph performed before and after surgery, the major curve at coronal
      plane was divided into three segments factitiously: upper segment (from the
      superior endplate of the upper vertebra of the major curve to the inferior
      endplate of the upper vertebra adjacent to the resected vertebra), middle segment
      (from the inferior endplate of the upper vertebra adjacent to the resected
      vertebra to the superior endplate of the lower vertebra of the resected
      vertebra), and lower segment (from the superior endplate of the lower vertebra of
      the resected vertebra to the inferior endplate of the lower end vertebra of the
      major curve). Cobb method was used to measure the curvature of the major curve
      and each segment. We analyzed the changes of the Cobb angle in the major curve
      and each segment. We also analyzed the correlation between the placement of
      pedicle screws and deformity correction. RESULTS: The Cobb angle of the major
      curve decreased from 110.1 +/- 18.1 degrees  to 51.0 +/- 17.3 degrees  (p < 0.05)
      after surgery (decreased by 59.1 +/- 16.4 degrees ), the mean correction rate was
      54.1 +/- 12.2% (p < 0.05). The Cobb angle of the middle segment decreased by 28.1
      +/- 14.7 degrees  (p < 0.05), the contribution rate was 49.1 +/- 27.3%. The upper
      and lower segments decreased by 15.7 +/- 13.1 degrees  and 15.3 +/- 12.4 degrees
      , respectively (p < 0.05). There were no significant differences in the
      contribution rate between upper and lower segments (25.2 +/- 16.6% vs. 26.3 +/-
      22.6%) (p > 0.05). 22 patients were instrumented with at least one pedicle screw
      in the adjacent upper and lower vertebras of the resected vertebra and gained a
      better corrective effect in comparison with the others (p < 0.05). The data also
      indicated that deformity correction was closely related to the numbers of the
      pedicle screws (r = 0.82, p < 0.05). CONCLUSION: In conclusion, the middle
      segment offered the highest contribution rate to the deformity correction of the
      major curve, but at the same time the spinal cord was angulated in this segment.
      So, it is dangerous to gain too much deformity correction in the middle segment.
      Because spine would shorten and the tension in spinal cord would decrease after
      vertebral column resection, a better correction effect could be gained in upper
      and lower segments at a low risk of spinal cord injury. But it was actually too
      hard for such rigid spinal deformity. It could gain a better corrective effect
      and stability by placing more pedicle screws at major curve, especially at the
      upper and lower vertebras adjacent to the resected vertebra, but sometimes it was
      difficult to place enough pedicle screws in severe rigid spinal deformities.

PMID- 21898166
TI  - Endovascular treatment of multiple HIV-related aneurysms using multilayer stents.
AB  - Complex peripheral aneurysm anatomy with major artery branches in the immediate
      vicinity and mycotic aneurysm often impede endovascular management using covered
      stent grafts. The Cardiatis Multilayer Stent (Cardiatis, Isnes, Belgium) is a
      recently approved innovative stent system for peripheral aneurysm management. Its
      multilayer design aims at decreasing mean velocity and vorticity within the
      aneurysm sac to cause thrombus formation while maintaining patency of branching
      vessels due to laminar flow. We present a case of bilateral subclavian artery
      aneurysms and perivisceral aortic aneurysms in an AIDS patient successfully
      treated with the Cardiatis Multilayer Stent at 18 months' follow-up.

PMID- 21898167
TI  - No evidence for a role of xenotropic murine leukaemia virus-related virus and BK
      virus in prostate cancer of German patients.
AB  - Prostate cancer is one of the most prevalent types of cancer in men.
      Controversial data exist concerning the role of BKPyV and the xenotropic murine
      leukaemia virus-related gammaretrovirus (XMRV) in prostate cancer development. We
      therefore assessed the association between prostate cancer and viral infections.
      We could detect BKPyV in only 1 out of 85 prostate cancer samples, whereas none
      of the tissue samples showed evidence for XMRV positivity. Lack of detection of
      BKPyV and XMRV in prostate cancer tissues suggests that these viruses do not play
      a role in the pathogenesis of this type of cancer.

PMID- 21898168
TI  - Face off: searching for truth and beauty in the clinical encounter. Based on the
      memoir, autobiography of a face by Lucy Grealy.
AB  - Based on Lucy Grealy's memoir, Autobiography of a Face, this article explores the
      relationship between gender and illness in our culture, as well as the paradox of
      "intimacy without intimacy" in the clinical encounter. Included is a brief review
      of how authenticity, vulnerability, and mutual recognition of suffering can
      foster the kind of empathic doctor-patient relationship that Lucy Grealy sorely
      needed, but never received. As she says at the end of her memoir, "All those
      years I'd handed my ugliness over to people, and seen only the different ways it
      was reflected back to me."

PMID- 21898169
TI  - Tasty but protected--first evidence of chemical defense in oribatid mites.
AB  - Oribatid mites (Acari, Oribatida) represent one of the most abundant and speciose
      groups of microarthropods in the decomposer food webs of soils, but little is
      known of their top-down regulation by predators. Oribatids are relatively long
      lived and have numerous morphological defensive adaptations, and so have been
      proposed to live in 'enemy-free space'. Most also possess a pair of large
      exocrine oil glands that produce species-specific mixtures of hydrocarbons,
      terpenes, aromatics, and alkaloids with presumably allomonal functions, although
      their adaptive value has never been tested empirically. We developed a protocol
      that discharges the oil glands of the model oribatid species, Archegozetes
      longisetosus. and offered 'disarmed' individuals as prey to polyphagous Stenus
      beetles (Staphylinidae), using untreated mites as controls. Stenus juno fed on
      disarmed mites with behavioral sequences and success rates similar to those
      observed when they prey on springtails, a common prey. In contrast, mites from
      the control group with full glands were almost completely rejected; contact with
      the gland region elicited a strong reaction and cleaning behavior in the beetle.
      This is the first evidence of an adaptive value of oribatid mite oil gland
      secretions for chemical defense. The protocol of discharging oil glands should
      facilitate future studies on top-down control of oribatid mites that aim to
      differentiate between morphological and chemical aspects of defensive strategies.

PMID- 21898170
TI  - Central giant cell lesion.
AB  - A classic case of central giant cell lesion (CGCL) is presented with emphasis on
      clinical, radiologic, and histologic features. The differential is discussed
      including peripheral giant cell granuloma, brown tumor of hyperparathyroidism,
      and giant cell tumor of bone. The molecular pathway of osteoclastogenesis is
      selectively reviewed and applied to suggest possible etiologies of the giant cell
      lesions. CGCL syndromes and treatment are also discussed.

PMID- 21898171
TI  - Prevalence and psychosocial correlates of perinatal depression: a cohort study
      from urban Pakistan.
AB  - Depression around childbirth is common in low income countries. The aim of this
      study was to examine the factors associated with persistence of depression from
      the antenatal to the postnatal period in urban Pakistan. A total of 1,357
      pregnant women in their third trimester attending the antenatal clinic were
      included in the study. From these, 763 mothers who delivered at the study
      maternity home were reassessed after 3 months of childbirth. Edinburgh Postnatal
      Depression Scale (EPDS) was administered to measure depression in both the
      antenatal and the postnatal periods. Psychological distress, disability and life
      events experienced by mothers were also measured by using the Self-Reporting
      Questionnaire (SRQ-20), Brief Disability Questionnaire (BDQ), and Life Events
      Checklist, respectively. We found 25.8% prevalence rate of antenatal depression
      and 38.3% persistent depression in a private clinic. Persistently depressed
      mothers had significantly high psychological distress, more disability, and
      experienced more stressful life events than the resolved group. Our findings
      confirm the high rates of depression during pregnancy but we found low rates of
      persistent depression in this urban population as compared to the previous
      report. There is a need for further investigation of factors associated with
      persistent depression in order to develop appropriate interventions.

PMID- 21898172
TI  - A model for dynamics of primer extension by eukaryotic DNA primase.
AB  - A mathematical model is proposed for processive primer extension by eukaryotic
      DNA primase. The model uses available experimental data to predict rate constants
      for the dynamic behavior of primase activity as a function of NTP concentration.
      The model also predicts some data such as the binding affinities of the primase
      for the DNA template and for the RNA primer.

PMID- 21898173
TI  - Differential effects of the adenosine A2A agonist CGS-21680 and haloperidol on
      food-reinforced fixed ratio responding in the rat.
AB  - RATIONALE: Previous studies have shown that adenosine A(2A) receptors are
      colocalized with dopamine D(2) receptors on striatal neurons. Activation of these
      two receptors has antagonistic effects under a number of conditions suggesting
      that stimulation of adenosine A(2A) receptors may have behavioral effects
      resembling those produced by blockade of dopamine D(2) receptors, but this
      possibility has been investigated in a limited number of situations. OBJECTIVE:
      We compared the effects of the adenosine A(2A) agonist CGS-21680 and the
      preferential D(2) dopamine antagonist haloperidol in a situation in which
      dopamine blockade produces a distinctive pattern of behavioral effects. MATERIALS
      AND METHODS: Six rats were trained to lever press for food reward on a fixed
      ratio 15 schedule of reinforcement and then tested after being injected with
      various doses of CGS-21680 (0.064, 0.128, and 0.25 mg/kg) and haloperidol (0.25
      and 0.1 mg/kg). RESULTS: Haloperidol produced a dose-dependent suppression of
      lever pressing with mean response rates declining across the duration of the test
      session. CGS-21680 also produced a dose-dependent suppression of responding, but
      this effect was not temporally graded, and responding was equivalently suppressed
      across the duration of the session. Additionally, CGS-21680 increased post
      reinforcement pause duration to a much greater extent than did haloperidol.
      CONCLUSIONS: On this task, the behavioral effects of CGS-21680 do not resemble
      those produced by haloperidol. Several explanations of this discrepancy are
      possible, the most likely being that the observed behavioral effects of CGS-21680
      result from an action at a site other than D(2) receptor-expressing striatal
      neurons.

PMID- 21898174
TI  - Methotrexate dose delivery is more important than ciclosporin level in graft
      versus-host disease prophylaxis following T-replete reduced-intensity sibling
      allogeneic stem cell transplant.
AB  - We investigated the contributions of methotrexate (MTX) and ciclosporin (CsA)
      prophylaxis to acute/chronic graft-versus-host disease (a/cGvHD) prevention
      following reduced-intensity conditioned allogeneic haematopoietic stem cell
      transplant (HSCT). Ninety-two fludarabine-melphalan sibling allo-SCT received
      CsA. Nine, 30 and 47 patients received no MTX, 2-3 doses and 4 doses,
      respectively. Cumulative CsA blood level to day 21 (CsA(21)) was calculated.
      Grades II-IV aGvHD incidence was 37.2%. In multivariate analysis, MTX omission
      and increasing donor age significantly associated with aGvHD incidence whilst MTX
      reduction and CsA(21) did not. Median duration of first immunosuppressive therapy
      (IST) for aGvHD was 68 days; duration of first IST was significantly longer in
      older patients but was not associated with MTX or CsA(21). Extensive cGvHD
      incidence was 60.6% at 1 year. Reduction of MTX to 2-3 doses, but not MTX
      omission or CsA(21), was associated with greater incidence of cGvHD affecting >=3
      organs. Median IST duration was 22 months; neither MTX nor CsA(21) influenced
      this. IST duration was significantly greater in patients receiving a CD34 dose
      below median. Neither MTX nor CsA(21) altered survival or relapse outcomes. MTX
      influences GvHD following T-replete RIC sibling HSCT.

PMID- 21898175
TI  - Laparoscopic excision of esophageal leiomyoma.
AB  - Esophageal leiomyoma is the most common benign tumor of the esophagus. The lower
      and middle thirds of the esophagus are the most frequent locations of these
      tumors and in about one-third of the patients they occur at the level of the
      gastroesophageal junction. They are less than 5 cm in size in 50% of the
      patients. A left thoracotomy, thoracoscopy or a laparoscopic approach can be used
      for lesions in the lower third of the esophagus. Esophageal leiomyomas should be
      considered for resection when symptomatic. Preoperative evaluation allows precise
      characterization of the diagnosis and location. Minimally invasive surgery is
      considered today the treatment of choice with the laparoscopic approach used for
      distal tumors. We present the case of a 63-year-old woman with an esophageal
      leiomyoma located above the gastroesophageal junction who underwent a successful
      laparoscopic excision of the tumor.

PMID- 21898178
TI  - Evaluation of a new automated chemiluminescence immunoassay for FGF23.
AB  - Fibroblast growth factor 23 (FGF23) is a hormone regulating phosphate and vitamin
      D metabolism. We have previously established a sandwich enzyme-linked
      immunosorbent assay (ELISA) for FGF23 and reported that FGF23 values are useful
      for the differential diagnosis of chronic hypophosphatemia. However, this ELISA
      has a rather narrow assay range of 3-800 pg/ml, and it was pointed out that the
      assay performance is not satisfactory when automatic washing is used. Here we
      evaluated a new automated chemiluminescence immunoassay for FGF23. This assay
      uses 10 MUl sera or plasma samples and requires 20 min to obtain the first
      result. The assay was linear up to about 15,000 pg/ml and had a detection limit
      of 1 pg/ml. In addition, this assay showed coefficients of variation of less than
      5% using samples with average FGF23 levels of 43.2-2,454.0 pg/ml. When FGF23
      levels in 210 samples from chronic hypophosphatemic patients were evaluated by
      both the previous ELISA and this new assay, there was a good correlation of R (2)
      = 0.96. However, FGF23 levels by the new assay showed lower values, especially in
      samples with high FGF23 levels. Given that the lowest FGF23 level in patients
      with FGF23-related hypophosphatemia was 30.8 pg/ml and that the highest FGF23
      levels in patients with non-FGF23-related hypophosphatemia was 20.8 pg/ml by this
      novel assay, the sensitivity and specificity were 100% when the cutoff was set
      between 20.8 and 30.8 pg/ml. From the aspect of convenience and the coefficients
      of variation of this assay, we propose that the cutoff be 25 pg/ml. There results
      indicate that this new assay is ideal for both clinical use and clinical studies,
      especially when measuring many samples with high FGF23 levels.

PMID- 21898177
TI  - Harmful lifestyles on orthopedic implantation surgery: a descriptive review on
      alcohol and tobacco use.
AB  - Alcohol abuse and smoking habits have adverse effects on bone health and are a
      risk factor for osteoporosis, fractures and impaired fracture repair.
      Osteointegration processes around implanted biomaterials involve a coordinated
      cascade of complex events that are very similar to those occurring during
      fracture repair and require a suitable microenvironment and the coordinated
      action of cells and signal molecules. Therefore, diseases and harmful lifestyles
      that impair the normal bone healing process can reduce the success of implant
      surgery and may negatively influence the osteointegration of prostheses and
      implant devices for fracture fixation such as screws, nails and plates.
      Understanding the effects of harmful lifestyles on bone implant osteointegration
      is important for successful implant therapy, orthopedic reconstructive surgery
      and tissue-engineered-based therapies. However, the mechanisms by which smoking
      and alcoholism affect bone metabolism, bone mass and the balance of bone
      resorption and formation, also in the presence of an orthopedic implant, are not
      completely understood and remain inadequately elucidated. This review aims to
      analyze in vitro and in vivo studies regarding orthopedic implant integration in
      the presence of tobacco smoking and alcohol consumption with a focus on
      pathophysiology and local or systemic mechanisms of action on bone.

PMID- 21898179
TI  - Relevance of selenoprotein transcripts for selenium status in humans.
AB  - The most commonly used methods for assessing the selenium (Se) status in humans
      involve analysis of Se concentration, selenoprotein activity, and concentration
      in the blood and its compartments. Recently, it has been suggested that the
      expression of selenoprotein mRNA in circulating blood leukocytes could
      differently reflect Se status, due to prioritization of specific selenoprotein
      synthesis in response to dietary Se supply. Whereas the Se levels required for
      optimization of selenoprotein P level and plasma glutathione peroxidise activity
      are well known, estimation of Se level that is required for maximal mRNA
      expression of selenoprotein in humans is the subject of current investigations.
      Studies on rats suggest that whole blood selenoprotein mRNA level can be used as
      the relevant molecular biomarker for assessing Se status, and suboptimal Se
      intake may be sufficient to achieve effective expression. Human studies, however,
      did not confirm this hypothesis. According to studies on rodents and humans
      discussed in this review, it appears that suboptimal Se intake may be sufficient
      to satisfy molecular requirements of Se and it is lower than current recommended
      dietary intake in humans. The use of selenoprotein transcripts as a molecular
      biomarker of Se status requires further studies on a large group of healthy
      individuals with different baseline Se, including data regarding genetic
      polymorphism of selenoproteins and data regarding potential modifiers of Se
      metabolism.

PMID- 21898180
TI  - Risk stratification of survival by lymphovascular invasion, pathological stage,
      and surgical margin in patients with bladder cancer treated with radical
      cystectomy.
AB  - BACKGROUND: The aim of this study was to investigate prognostic factors and
      develop a prognostic factor-based risk stratification model for disease-specific
      survival (DSS) in a radical cystectomy (RC) series. METHODS: The patient cohort
      comprised 194 consecutive patients with bladder cancer treated with RC.
      Univariate and multivariate Cox proportional hazard model analyses were performed
      to identify significant prognostic factors for DSS. A risk stratification model
      was developed based on the relative risks (RRs) of DSS. RESULTS: Median follow-up
      period was 26.8 months. The 1-, 3-, and 5-year DSS were 88.0, 74.0, and 64.9%,
      respectively. In the univariate analysis, pathological T (pT) (>= pT2),
      lymphovascular invasion (LVI), non-urothelial carcinoma component, surgical
      margin (SM), and lymph node metastases (pN) were significantly associated with
      poor prognosis. In the multivariate analysis, pT (>= pT2), LVI, and SM were
      independent factors for predicting poor prognosis. Based on these results,
      patients were stratified into three risk groups: low (RR = 1.00-3.626),
      intermediate (5.860-9.826), and high (21.24). The 1-, 3-, and 5-year survival
      rates were 96.9, 85.1, and 85.1% in the low-risk group, 83.0, 63.4, and 43.8% in
      the intermediate group, and 51.0, 19.4, and 19.4% in the high-risk group,
      respectively. The differences among these groups were significant. CONCLUSIONS:
      In our RC series, pT (>= pT2), LVI, and SM were independent prognostic factors.
      This information may be useful to identify patients with poor prognosis, who
      might be good candidates for innovative treatment.

PMID- 21898181
TI  - Prognostic significance of breast cancer subtype and p53 overexpression in
      patients with locally advanced or high-risk breast cancer treated using upfront
      modified radical mastectomy with or without post-mastectomy radiation therapy.
AB  - BACKGROUND: Although post-mastectomy radiation therapy (PMRT) has shown benefits,
      its effects in patient subpopulations remain uncertain. Therefore, we assessed
      whether breast cancer subtype and p53 overexpression were associated with outcome
      after modified radical mastectomy (MRM), with or without PMRT. METHODS: We
      retrospectively analyzed the records of patients who underwent MRM, with or
      without PMRT, between January 1991 and December 2008. Patients were considered
      eligible if they had T3 or T4 stage disease; any T stage with N2 or N3 stage; any
      T or N stage with positive, close (<1 mm) resection margins; or skin, nipple, or
      pectoral muscle invasion. We used immunohistochemistry and/or fluorescent in situ
      hybridization to determine breast cancer subtypes and p53 overexpression status.
      RESULTS: We found that 104 patients were eligible, including 59 (56.7%) who
      underwent PMRT and 45 (43.3%) who did not. Median follow-up duration was 61.3
      months (range 16.1-232.7). Overall survival (OS) was significantly longer in
      patients who underwent PMRT (P = 0.029). This trend was evident in the subgroup
      of luminal type A breast cancer (P = 0.017) and non-p53 overexpression (P =
      0.026) patients. However, there was no significant survival benefit from PMRT in
      the subgroup of triple negative (TN) breast cancer (P = 0.528) and p53
      overexpression (P = 0.189) patients. CONCLUSIONS: The benefit of PMRT differed
      among subgroups with different breast cancer subtype and p53 overexpression. More
      efficacious systemic treatment strategies are needed, especially in patients at
      high risk for distant metastasis, to obtain optimal therapeutic gain.

PMID- 21898182
TI  - Leptospirosis as the most frequent infectious disease impairing productivity in
      small ruminants in Rio de Janeiro, Brazil.
AB  - Despite the importance of small ruminants breeding in developing countries,
      milk/meat productivity remains unsatisfactory. Infectious diseases, such as
      leptospirosis, brucellosis, and small ruminant lentiviruses (SRLVs), contribute
      to this scenario. The objective of the present study was to determine the role of
      each of these diseases in the productivity of small ruminants breeding in Rio de
      Janeiro, Brazil. In goats, 343 samples were tested for leptospirosis, 560 for
      Brucella abortus, and 506 for caprine arthritis-encephalitis (CAE), whereas in
      sheep, 308 samples were tested for leptospirosis, 319 for B. abortus, 374 for
      Brucella ovis, and 278 for Maedi-Visna (MV). Regarding leptospirosis, 25.9% of
      goats and 47.4% sheep were seroreactive, with serovar Hardjo the most prevalent
      in both species. Anti-B. abortus agglutinins were found in 0.7% of all samples,
      exclusively in goats. In relation to SRLVs, 8.6% of goats and 3.2% of sheep
      samples were positive for CAE and MV, respectively. Leptospirosis was the major
      infectious problem in the small ruminants sampled and may contribute to impaired
      productivity of these animals.

PMID- 21898183
TI  - First report of Neospora caninum infection in cattle in Sudan.
AB  - A cross-sectional survey was conducted in Sudan to determine sero-prevalence and
      risk factors associated with Neospora caninum infection in non-vaccinated dairy
      herds and to assess importance of the disease. Blood samples were collected from
      a total of 262 animals from 25 herds. Sera were tested for antibodies against N.
      caninum using ELISA test. The prevalence rates of N. caninum antibodies in cattle
      were high both at herd level (44%) and at individual animal level (10.7%). Herd
      level infection rates were similar in Khartoum State (43.7%) and at Gazira States
      (44.4%). The overall prevalence rates were higher (16.1%) in Gazira State than in
      Khartoum State (9%) but with no significant variation. The sero-prevalence at
      individual animal level was significantly higher (p < 0.05) in animals with
      history of abortion (12.8%) than in apparently healthy animal (11.3%), animal
      with history of infertility (8.1%), or neonatal death of calves (4.3%). In
      addition, significantly higher (P < 0.05) sero-prevalence was observed in samples
      collected during the rainy season (6.87%) than winter (3.05%) or summer (0.76%).
      However, no significant differences in sero-prevalence due to locality, animal
      breed, sex, and age were observed (p > 0.05). This preliminary study reveals for
      the first time the existence of natural N. caninum infection in Sudan. Also, the
      findings of the present study indicated that this disease is highly prevalent in
      two major areas of dairy production in the country, and this calls for control
      strategy to be implemented.

PMID- 21898184
TI  - Cluvenone induces apoptosis via a direct target in mitochondria: a possible
      mechanism to circumvent chemo-resistance?
AB  - The synthetic caged Garcinia xanthone, cluvenone, has potent and selective
      cytotoxicity against numerous cancer cell lines including those that are multi
      drug resistant. The direct target of this structurally and functionally unique
      agent is unknown and that of the parent natural product, gambogic acid (GA),
      presently in clinical trials, is not yet entirely clear. For the first time,
      using fluorescently labeled GA (GA-Bodipy), we determined that GA-Bodipy
      localized in mitochondria and was effectively displaced by cluvenone in
      competition experiments indicating that the direct target of cluvenone resided in
      mitochondria and was shared by GA. In agreement with these findings, treatment of
      HeLa cells with cluvenone or GA resulted in disruption of mitochondrial
      morphology within 4 h. Furthermore, experiments using the potential sensitive JC
      1 dye demonstrated that cells treated with 1 MUM cluvenone for 1 h had
      significant loss of MMP compared to control cells. Examination of Cyt c levels in
      leukemia cells treated with 1 MUM cluvenone resulted in a 4-fold increase in
      levels of both cytosolic and mitochondrial Cyt c. In agreement with Cyt c
      release, caspase 9 activity was increased 2.6-fold after treatment of cells for 5
      h with 1 MUM cluvenone. Remarkably, the caspase-9 inhibitor, Z-LEHD-FMK, blocked
      cluvenone-induced apoptosis in a dose-dependent manner with apoptosis being
      completely blocked by 10 MUM of the inhibitor. In conclusion, cluvenone, an agent
      with potent cytotoxicity against multi-drug resistant tumor cells, has direct
      targets in mitochondria thus setting precedence for drug discovery efforts
      against these targets in the treatment of refractory cancers.

PMID- 21898185
TI  - [Surgery in the sitting position : anesthesiological considerations].
AB  - Surgical interventions in the sitting position are intended to optimize surgical
      conditions by reducing bleeding in the operation field and improving the surgical
      approach. There are, however, some potentially life-threatening risks associated
      with surgery in the sitting position. Of these risks, air embolism is one of the
      most serious complications and should be detected immediately in order to
      initiate specific countermeasures. In addition to standard monitoring procedures,
      transthoracic Doppler ultrasound and transesophageal echocardiography are
      valuable methods used to detect the presence of air in the vasculature. If an air
      embolism becomes apparent, further targeted measures are needed to prevent or
      aggressively treat the progression of potentially life-threatening consequences.

PMID- 21898186
TI  - Improved aortic enhancement in CT angiography using slope-based triggering with
      table speed optimization: a pilot study.
AB  - To assess whether a scan triggering technique based on the slope of the time
      attenuation curve combined with table speed optimization may improve arterial
      enhancement in aortic CT angiography compared to conventional threshold-based
      triggering techniques. Measurements of arterial enhancement were performed in a
      physiologic flow phantom over a range of simulated cardiac outputs (2.2-8.1
      L/min) using contrast media boluses of 80 and 150 mL injected at 4 mL/s. These
      measurements were used to construct computer models of aortic attenuation in CT
      angiography, using cardiac output, aortic diameter, and CT table speed as input
      parameters. In-plane enhancement was calculated for normal and aneurysmal aortic
      diameters. Calculated arterial enhancement was poor (<150 HU) along most of the
      scan length using the threshold-based triggering technique for low cardiac
      outputs and the aneurysmal aorta model. Implementation of the slope-based
      triggering technique with table speed optimization improved enhancement in all
      scenarios and yielded good- (>200 HU; 13/16 scenarios) to excellent-quality (>300
      HU; 3/16 scenarios) enhancement in all cases. Slope-based triggering with table
      speed optimization may improve the technical quality of aortic CT angiography
      over conventional threshold-based techniques, and may reduce technical failures
      related to low cardiac output and slow flow through an aneurysmal aorta.

PMID- 21898187
TI  - Molecular characterization and complete genome analysis of human enterovirus 71
      and coxsackievirus A16 from children with hand, foot and mouth disease in
      Thailand during 2008-2011.
AB  - Hand, foot and mouth disease (HFMD) has mostly been caused by enterovirus 71
      (EV71) and coxsackievirus A16 (CA16). CA 16 was the most common cause of HFMD in
      2010. EV71 had a high prevalence in 2008-2009 and has been identified with a
      higher frequency since 2011. Nearly complete genome sequences of three EV71
      strains (2008-2009 strains) and two CA16 strains (2010 strains) obtained from
      outbreaks in Thailand in 2008 to 2010 were characterized. Based on a phylogenetic
      tree of the complete VP1 region, three EV71 strains grouped into the B5, C1 and
      C4 genotypes, and two CA16 strains grouped into the C genotype. Based on sequence
      analysis, nucleotide changes were found to cluster in the internal ribosome entry
      site (IRES) element of the 5'-untranslated region (5'-UTR). Amino acid
      differences identified in all strains were located in the non-structural protein.
      These data also provide the molecular epidemiology of EV71 and CA16 outbreaks in
      Thailand.

PMID- 21898188
TI  - Surgical clipping as the preferred treatment for aneurysms of the middle cerebral
      artery.
AB  - OBJECTIVE: In recent years the endovascular treatment of intracranial aneurysms
      (coiling) has progressively gained recognition, particularly after the
      publication of the International Subarachnoid Aneurysm Trial (ISAT) in 2002.
      Despite the fact that in ISAT middle cerebral artery (MCA) aneurysms were clearly
      underrepresented, the study is often used as an argument to favor coiling above
      surgery in MCA aneurysms. Taken into account that MCA aneurysms are very well
      accessible for surgery, a contemporary assessment of the benefits of a preferred
      surgical strategy for MCA aneurysms was performed in a tertiary neurovascular
      referral center. METHODS: A prospectively kept single-center database of 151
      consecutive patients with an MCA aneurysm was reviewed over a 6-year period (2001
      2006). Long-term follow-up after surgical treatment of a ruptured MCA aneurysm
      was obtained in 74 out of 77 (96%) patients. The outcome was compared with
      relevant series in the literature. RESULTS: After a mean follow-up of 4.7 years,
      59 out of 74 surgically treated patients (80%) with a ruptured MCA aneurysm had a
      good outcome (mRankin 0-2). All patients with an unruptured MCA aneurysm also had
      a good outcome after clipping. This is well-matched with the findings of the
      literature search, and competitive with the endovascular results. CONCLUSION:
      Surgical clipping is recommended as the principal treatment strategy for MCA
      aneurysms. This is not only ethically defendable in view of the surgical results
      but also in line with a strategy to maintain surgical experience within
      centralized neurovascular centers.

PMID- 21898189
TI  - KIR genotypic diversity can track ancestries in heterogeneous populations: a
      potential confounder for disease association studies.
AB  - Killer cell immunoglobulin-like receptors (KIR) are encoded by highly polymorphic
      genes that regulate the activation of natural killer (NK) cells and other
      lymphocyte subsets and likely play key roles in innate and adaptive immunity.
      Association studies increasingly implicate KIR in disease predisposition and
      outcome but could be confounded by unknown KIR genetic structure in heterogeneous
      populations. To examine this, we characterized the diversity of 16 KIR genes in
      712 Northern Californians (NC) stratified by self-assigned ethnicities and
      compared the profiles of KIR polymorphism with other US and global populations
      using a reference database. Sixty-eight distinct KIR genotypes were
      characterized: 58 in 457 Caucasians (NCC), 17 in 47 African Americans (NCAA), 21
      in 80 Asians (NCA), 20 in 74 Hispanics (NCH), and 18 in 54 "other" ethnicities
      (NCO). KIR genotype patterns and frequencies in the 4 defined ethnicities were
      compared with each other and with 34 global populations by phylogenetic analysis.
      Although there were no population-specific genotypes, the KIR genotype frequency
      patterns faithfully traced the ancestry of NCC, NCAA, and NCA but not of NCH
      whose ancestries are known to be more heterogeneous. KIR genotype frequencies can
      therefore track ethnic ancestries in modern urban populations. Our data emphasize
      the importance of selecting ethnically matched controls in KIR-based studies to
      avert spurious associations.

PMID- 21898190
TI  - [Continuous local wound infusion with local anesthetics :  For thoracotomy and
      major abdominal interventions].
AB  - Wound infusion with local anesthetics is a nearly 100 years old proven and secure
      analgesic method. Recently special wound infusion catheters have become available
      which can be placed intraoperatively into the wound under direct supervision of
      the surgeon to infuse local anesthetics and optimize postoperative analgesia. For
      thoracotomy this method was modified to improve its efficacy and the catheters
      are used to establish a continuous paravertebral intercostal nerve block (PVB).
      Many studies have confirmed the analgesic power of PVB which results in a pain
      reduction comparable to thoracic epidural analgesia (TEA) but without TEA
      specific side-effects, in particular hypotension. The efficacy of continuous
      local wound infusion (CLWI) is less obvious for laparotomy. If fundamental
      preconditions for this loco-regional method are considered (indications, choice
      of catheter, local anesthetic dose) the laparotomy wound could also be suitable
      for the use of CLWI. According to the literature currently available CLWI is not
      associated with an increased risk of wound infections.

PMID- 21898191
TI  - Non-verbal number acuity correlates with symbolic mathematics achievement: but
      only in children.
AB  - The process by which adults develop competence in symbolic mathematics tasks is
      poorly understood. Nonhuman animals, human infants, and human adults all form
      nonverbal representations of the approximate numerosity of arrays of dots and are
      capable of using these representations to perform basic mathematical operations.
      Several researchers have speculated that individual differences in the acuity of
      such nonverbal number representations provide the basis for individual
      differences in symbolic mathematical competence. Specifically, prior research has
      found that 14-year-old children's ability to rapidly compare the numerosities of
      two sets of colored dots is correlated with their mathematics achievements at
      ages 5-11. In the present study, we demonstrated that although when measured
      concurrently the same relationship holds in children, it does not hold in adults.
      We conclude that the association between nonverbal number acuity and mathematics
      achievement changes with age and that nonverbal number representations do not
      hold the key to explaining the wide variety of mathematical performance levels in
      adults.

PMID- 21898192
TI  - Worldwide distribution of type II diabetes-associated TCF7L2 SNPs: evidence for
      stratification in Europe.
AB  - Type II diabetes is a multifactorial disease with a complex etiology. Numerous
      genes have been implicated in disease pathogenesis. In particular, SNPs at the
      TCF7L2 locus have consistently shown strong associations with type II diabetes.
      This study characterizes the global distribution of type II diabetes-associated
      TCF7L2 SNPs utilizing HapMap, HGDP-CEPH, and Alfred databases and the literature.
      High frequencies of rs7903146(T), rs12255372(T), and rs7901695(C) SNPs are
      observed in Africa, Europe, and the Middle East, but they are reduced and almost
      absent in Southeast Asian and Native American populations. In contrast,
      rs11196218(A) has the highest frequency in Eurasia but is reduced in sub-Saharan
      African and Native American populations. Regional variations in rs7903146(T)
      follow a gradient of decreasing frequency from southern into northeastern Europe.
      These findings demonstrate extensive global and regional variations in the
      frequencies of TCF7L2 SNPs, which may contribute to differences in the incidence
      of type II diabetes worldwide.

PMID- 21898194
TI  - What's new on the dental scene? Browsing through the dental literature.

PMID- 21898196
TI  - Effects of fixed appliances in correcting Angle Class II on the depth of the
      posterior airway space: FMA vs. Herbst appliance--a retrospective cephalometric
      study.
AB  - OBJECTIVE: The objective of this retrospective study based on the metric
      evaluation of lateral cephalograms was to investigate the extent to which
      treatment with two different fixed appliances for the correction of Angle Class
      II influenced the morphology of the extrathoracic airway space (the posterior
      airway space, PAS). PATIENTS AND METHODS: A total of 43 patients with Angle Class
      II malocclusion were classified into two groups according to the appliance used
      for treatment: the functional mandibular advancer (FMA; n = 18) or the Herbst
      appliance (n = 25). Lateral cephalograms were taken of each patient at the start
      of functional jaw orthopedic treatment (time point T1) and at its completion
      (time point T2). Specific distances and angles were measured and analyzed in a
      cephalometric analysis. RESULTS: We observed major differences among the 43
      patients in the depth of the posterior airway space during treatment with fixed
      appliances for Angle Class II correction. Regression analysis revealed that
      changes in sagittal and vertical positions had different effects on the depth of
      specific PAS sections: increases in anterior facial height are associated
      proportionately with increases in PAS width, particularly in the upper region. On
      the other hand, increases in posterior facial height and in the mandible's
      forward displacement correlated inversely to the decreases in depth, particularly
      in the central and lower PAS regions. The two treatment appliances (FMA, Herbst
      appliance) had the same effects on extrathoracic airway depth. CONCLUSIONS:
      Analyses of lateral cephalograms indicate that Angle Class II treatment with
      fixed appliances does not prevent sleep apnea in patients at risk. Nevertheless,
      this study does not permit absolutely reliable conclusions about the dimensions
      of the pharyngeal airway space. As the lateral cephalogram provides good images
      of structures in the midsagittal plane but is incapable of imaging the transverse
      dimension, there is an automatic lack of information concerning the precise width
      and volume of the extrathoracic airway space.

PMID- 21898195
TI  - Accuracy of anatomical landmark identification using different CBCT- and MSCT
      based 3D images: an in vitro study.
AB  - OBJECTIVE: The aim of this study was to evaluate the reproducibility of
      anatomical landmarks and the accuracy of different cone-beam CTs (CBCTs/DVTs) and
      a multislice spiral CT (MSCT) scanner. METHODS: A human, fresh-frozen cadaver
      head was scanned with four CBCTs (Accuitomo 3D, 3D eXam, Pax Reve 3D, Pax Zenith
      3D) and one MSCT (SOMATOM Sensation 64) scanner. The three-dimensional (3D)
      reconstruction of the volume data sets and location of the anthropometric
      landmarks (n=11), together with linear (n=5) and angular (n=1) measurements were
      carried out by three examiners using the program VoXim(r) 6.1. The measurements
      were taken twice at a 14-day interval. Descriptive analyses were made and the
      standard deviations were used to compare differences in the accuracy of landmark
      identification. RESULTS: The descriptive statistics showed distinct differences
      in the reference points in the three axes of the coordinate system. Because of
      anatomical and morphological factors, the pogonion and gnathion reference points
      displayed higher standard deviations when set on the transverse plane (SD(CBCT)
      Pog: 0.66-1.57 mm; SD(MSCT) Pog: 0.14-1.09 mm; SD(CBCT) Gn: 1.05-1.77 mm;
      SD(MSCT) Gn: 0.20-0.85 mm), thus showing less accuracy. However, standard
      deviations on the sagittal and vertical planes were smaller. Genion, anterior
      nasal spine and infradentale had very low standard deviations on all three
      planes. The distance (Mfl-Mfr) and angle (Krl-Krr-Ge) revealed significantly
      smaller standard deviations in the MSCT (SD(CBCT) Krl-Krr-Ge: 0.51-0.75 mm;
      SD(MSCT) Krl-Krr-Ge: 0.22 mm). CONCLUSION: The CBCT devices evaluated in this
      study are suitable for taking exact 3D measurements of anatomical structures and
      meet all requirements for 3D cephalometric analysis.

PMID- 21898197
TI  - Severe external apical root resorption--local cause or genetic predisposition?
AB  - BACKGROUND: Current data suggest that a large extent of the variation in
      orthodontic root resorption may be explained by differences in individual genetic
      predisposition. This would imply, however, a similar root resorption reaction in
      all teeth. OBJECTIVE: To determine the incidence and extent of severe external
      apical root resorptions (SEARR) in maxillary incisors during multibracket (MB)
      appliance treatment. PATIENTS AND METHODS: Of the whole sample of patients having
      completed MB treatment at the University of Giessen between 1991 and 2010
      (P(Total)=3198), all subjects exhibiting severe root resorptions on at least one
      maxillary incisor were selected. SEARR were defined according to Malmgren et al.
      [39] (grade-IV RR=resorption >1/3 root length). Evaluation was performed using
      orthopantomograms from before and after MB treatment. The crown and root length
      of the affected teeth were measured. The extent of SEARR was assessed taking
      pretreatment crown length into consideration. RESULTS: SEARR was detected in 16
      patients. Thus, the incidence of SEARR on maxillary incisors during MB treatment
      totalled 0.5%. The median of SEARR of the affected incisors was 38.6% of the
      initial root length (minimum=33.4%, maximum=61.0%). Most subjects exhibited only
      single affected teeth. Only two subjects (0.06% absolute/12.5% relative)
      presented four maxillary incisors with SEARR. CONCLUSIONS: The incidence of SEARR
      on maxillary incisors during MB treatment (0.5%) was very low compared to the
      literature. With only 12.5% of SEARR patients presenting four affected teeth,
      local rather than systemic/genetic factors seem to have predisposed the present
      subjects to SEARR.

PMID- 21898199
TI  - Synopsis of the species of Myxidium Butschli, 1882 (Myxozoa: Myxosporea:
      Bivalvulida).
AB  - A synopsis of the species of Myxidium Butschli, 1882 (Myxozoa: Myxosporea:
      Bivalvulida) is presented. It includes a total of 232 nominal species, whose
      principal morphological and morphometric characteristics, site of infection
      within the host, and original hosts and locality are indicated in a tabulated
      format. A diagrammatic illustration of a spore of most of the species is also
      provided.

PMID- 21898201
TI  - Acanthocephaloides irregularis n. sp. (Acanthocephala: Arhythmacanthidae) from
      marine fishes off the Ukrainian Black Sea coast.
AB  - Acanthocephaloides irregularis n. sp. (Arhythmacanthidae) is described from four
      species of marine fishes in the Gulf of Odessa and Sukhyi Lyman, Ukrainan Black
      Sea waters, making it the tenth species of the genus. The hosts are the combtooth
      blenny Parablennius zvonimiri (Kolombatovic) (Blenniidae), the mushroom goby
      Ponticola eurycephalus (Kessler) (Gobiidae), the tubenose goby Proterorhinus
      marmoratus (Pallas) (Gobiidae) and the black-striped pipefish Syngnathus abaster
      Risso (Syngnathidae). The new species is most similar to its closest relative,
      Acanthocephaloides propinquus (Dujardin, 1845), in proboscis shape and armature
      (12 longitudinal rows of 5 hooks) and the shape of the trunk, reproductive system
      and lemnisci, but differs in having randomly distributed trunk spines. These
      trunk spines are organised in circular rings of individual spines separated by
      aspinose zones. The new species is also unique in having an anterior trunk
      collar, a very large triangular cephalic ganglion, nucleated pouches at the
      posterior end of the proboscis receptacle, and hooks and spines with roots
      bearing anterior manubria. Valid and invalid species of Acanthocephaloides Meyer,
      1932 are listed and a key to all ten species is included.

PMID- 21898200
TI  - Morphological and genetic analysis of three new species of Ceratomyxa Thelohan,
      1892 (Myxozoa: Myxosporea) from carcharhinid sharks off Australia.
AB  - Three new species of Ceratomyxa Thelohan, 1892 are described from the gall
      bladders of two species of carcharhinid sharks collected off Heron and Lizard
      Islands on the Great Barrier Reef, Australia. Ceratomyxa carcharhini n. sp. and
      C. melanopteri n. sp. are described from Carcharhinus melanopterus (Quoy &
      Gaimard), and Ceratomyxa negaprioni n. sp. is described from Negaprion acutidens
      (Ruppell). These species are the first ceratomyxids reported from Australian
      elasmobranchs, and this is the first paper to formally characterise a novel
      Ceratomyxa species from an elasmobranch using both morphology and small subunit
      ribosomal DNA sequence data. Maximum parsimony and Bayesian inference analyses of
      the SSU rDNA dataset revealed that ceratomyxids from elasmobranchs form a sister
      clade to that of species infecting marine teleosts and Palliatus indecorus
      Schulman, Kovaleva & Dubina, 1979. Furthermore, the only sequenced freshwater
      ceratomyxid, Ceratomyxa shasta Noble, 1950, fell outside the overall marine
      ceratomyxid clade. These data show that Ceratomyxa, as currently recognised, is
      polyphyletic and ignites discussion on whether Ceratomyxa should be split.
      However, further taxon sampling, particularly in freshwater systems, is required
      to establish relevant biological divisions within the genus.

PMID- 21898202
TI  - First record of the avian ectoparasite Philornis downsi Dodge & Aitken, 1968
      (Diptera: Muscidae) in Argentina.
AB  - Species of Philornis Meinert, 1890 (Diptera, Muscidae) are Neotropical dipterans
      that include species with parasitic larvae which feed on nestling birds. To date,
      all Philornis species that have been recorded from Argentina have parasitic
      subcutaneous larvae. Here, for the first time for Argentina, we report the
      finding of Philornis downsi Dodge & Aitken, 1968, a fly with a nest-dwelling,
      semi-haematophagous larva. This record, from the humid Chaco ecoregion of
      Argentina in the nest of a saffron finch Sicalis flaveola pelzelni Sclater,
      substantially extends the known distribution of this species. We also report the
      consensus sequences of the internal transcribed spacer 1 (ITS1) and ITS2 regions
      of three of the specimens for future reference and comparison. Further
      investigation is needed to determine whether Argentina is part of the historical
      range of P. downsi or, alternatively, represents a recent expansion of its range,
      perhaps due to climatic changes or other factors of global environmental
      variation.

PMID- 21898203
TI  - Species of Taeniacanthus Sumpf, 1871 (Crustacea: Copepoda: Taeniacanthidae)
      parasitic on boxfishes (Tetraodontiformes: Aracanidae and Ostraciidae) from the
      Indo-West Pacific region, with descriptions of two new species.
AB  - Two new copepod species of the genus Taeniacanthus Sumpf, 1871 (Cyclopoida:
      Taeniacanthidae) are described from boxfishes (Aracanidae and Ostraciidae) caught
      in the Indo-West Pacific region: T. larsonae n. sp. from Ostracion nasus Bloch in
      the Arafura Sea and off Australia and Tetrosomus concatenatus (Bloch) off Japan;
      and T. thackerae n. sp. from O. immaculatus Temminck & Schlegel off Palau, O.
      rhinorhynchos Bleeker off Australia, Lactoria cornuta (Linnaeus) and Ostracion
      sp. off Japan, and Kentrocapros aculeatus (Houttuyn) in the East China Sea. T.
      larsonae n. sp. differs from its congeners by having several rows of spinules on
      the large pectinate process of the antenna and by differences in the shape of the
      sclerotised plates on the rostral area and structure of the maxilliped. T.
      thackerae n. sp. can be distinguished from its congeners by differences in the
      shape of the sclerotised plates on the rostral area, the structure of the
      maxilliped and ornamentation pattern of legs 1-4. Supplemental information for
      the female of Taeniacanthus ostracionis (Richiardi, 1870) and T. moa (Lewis,
      1967), as well as the first description of the male of T. moa, are also provided
      based on new material collected from ostraciid hosts caught in the Arafura Sea
      and off Australia, Indonesia and Japan. The four taeniacanthid species reported
      from boxfishes exhibit variable levels of host-specificity and have broad
      geographical ranges within the Indo-West Pacific region.

PMID- 21898204
TI  - Selective fluoroalkylation of organic compounds by tackling the "negative
      fluorine effect".
AB  - The presence of fluorine on a carbanion center will dramatically influence the
      nucleophilic alkylation reactions. Based on our own experience, we noticed that
      the fluorine substitution on the carbanionic carbon poses a negative effect in
      many nucleophilic fluoroalkylation reactions [we propose this effect as "negative
      fluorine effect (NFE)"]. Two factors were believed to contribute to the NFE: (1)
      thermal instability of fluorinated carbanions caused by alpha-elimination (self
      decomposition) and (2) the intrinsic nucleophilicity of fluorinated carbanion
      influenced by the fluorine atoms (such as hard/soft nature of the fluorinated
      carbanions). By tackling the NFE, our research group has attempted to design
      nucleophilic fluoroalkylation reactions with fluorinated sulfones and related
      reagents. These results were summarized as four methods to modulate the
      fluoroalkylation reactions: (1) changing the number of fluorine atoms, (2)
      slightly changing the neighboring groups, (3) changing the metal counterion,
      including using carbon-metal covalent bond to tune the reactivity, and (4)
      enhancing the generation of carbene species.

PMID- 21898205
TI  - Site-directed spin labeling of membrane proteins.
AB  - EPR spectroscopy of site-directed spin labeled membrane proteins is at present a
      common and valuable biophysical tool to study structural details and
      conformational transitions under conditions relevant to function. EPR is
      considered a complementary approach to X-ray crystallography and NMR because it
      provides detailed information on (1) side chain dynamics with an exquisite
      sensitivity for flexible regions, (2) polarity and water accessibility profiles
      across the membrane bilayer, and (3) distances between two spin labeled side
      chains during protein functioning. Despite the drawback of requiring site
      directed mutagenesis for each new piece of information to be collected, EPR can
      be applied to any complex membrane protein system, independently of its size.
      This chapter describes the state of the art in the application of site-directed
      spin labeling (SDSL) EPR to membrane proteins, with specific focus on the
      different types of information which can be obtained with continuous wave and
      pulsed techniques.

PMID- 21898206
TI  - Recent developments in (15)N NMR relaxation studies that probe protein backbone
      dynamics.
AB  - Nuclear Magnetic Resonance (NMR) relaxation is a powerful technique that provides
      information about internal dynamics associated with configurational energetics in
      proteins, as well as site-specific information involved in conformational
      equilibria. In particular, (15)N relaxation is a useful probe to characterize
      overall and internal backbone dynamics of proteins because the relaxation mainly
      reflects reorientational motion of the N-H bond vector. Over the past 20 years,
      experiments and protocols for analysis of (15)N R (1), R 2, and the heteronuclear
      (15)N-{(1)H} NOE data have been well established. The development of these
      methods has kept pace with the increase in the available static-magnetic field
      strength, providing dynamic parameters optimized from data fitting at multiple
      field strengths. Using these methodological advances, correlation times for
      global tumbling and order parameters and correlation times for internal motions
      of many proteins have been determined. More recently, transverse relaxation
      dispersion experiments have extended the range of NMR relaxation studies to the
      milli- to microsecond time scale, and have provided quantitative information
      about functional conformational exchange in proteins. Here, we present an
      overview of recent advances in (15)N relaxation experiments to characterize
      protein backbone dynamics.

PMID- 21898207
TI  - Molecular simulations of retention in chromatographic systems: use of biased
      Monte Carlo techniques to access multiple time and length scales.
AB  - The use of configurational-bias Monte Carlo simulations in the Gibbs ensemble
      allows for the sampling of phenomena that occur on vastly different time and
      length scales. In this review, applications of this simulation approach to probe
      retention in gas and reversed-phase liquid chromatographic systems are discussed.
      These simulations provide an unprecedented view of the retention processes at the
      molecular-level and show excellent agreement with experimental retention data.

PMID- 21898208
TI  - Solid-state NMR of inorganic semiconductors.
AB  - Studies of inorganic semiconductors by solid-state NMR vary widely in terms of
      the nature of the samples investigated, the techniques employed to observe the
      NMR signal, and the types of information obtained. Compared with the NMR of
      diamagnetic non-semiconducting substances, important differences often result
      from the presence of electron or hole carriers that are the hallmark of
      semiconductors, and whose theoretical interpretation can be involved. This review
      aims to provide a broad perspective on the topic for the non-expert by providing:
      (1) a basic introduction to semiconductor physical concepts relevant to NMR,
      including common crystal structures and the various methods of making samples;
      (2) discussions of the NMR spin Hamiltonian, details of some of the NMR
      techniques and strategies used to make measurements and theoretically predict NMR
      parameters, and examples of how each of the terms in the Hamiltonian has provided
      useful information in bulk semiconductors; (3) a discussion of the additional
      considerations needed to interpret the NMR of nanoscale semiconductors, with
      selected examples. The area of semiconductor NMR is being revitalized by this
      interest in nanoscale semiconductors, the great improvements in NMR detection
      sensitivity and resolution that have occurred, and the current interest in
      optical pumping and spintronics-related studies. Promising directions for future
      research will be noted throughout.

PMID- 21898209
TI  - Real-time PCR and multiplex approaches.
AB  - Analysis of RNA expression levels by real-time reverse-transcription (RT) PCR has
      become a routine technique in diagnostic and research laboratories. Monitoring of
      DNA amplification can be done using fluorescent sequence-specific probes, which
      generate signal only upon binding to their target. Numerous fluorescent dyes with
      unique emission spectra are available and can be used to differentially label
      probes for various genes. Such probes can be added to the same PCR amplification
      reaction for simultaneous detection of multiple targets in a single assay. Such
      multiplexing is advantageous, since it markedly increases throughput and
      decreases costs and labor. Here, we describe application of multiplex real-time
      RT-PCR using TaqMan probes in the analysis of relative expression levels of a
      novel tumor-associated gene CUG2 in cell lines and tissue samples.

PMID- 21898210
TI  - Reverse-transcriptase polymerase chain reaction to detect extracellular mRNAs.
AB  - The presence of extracellular nucleic acids has been reported in serum/plasma
      from cancer and diabetes patients that may help in disease diagnosis. Taking
      insulin-producing cells as examples here, RT-PCR was used to investigate a
      correlation between the presence and amounts of extracellular mRNA(s) and cell
      mass and/or function. RT-PCR was performed on a range of mRNAs, including Pdx1,
      Npy, Egr1, Pld1, Chgb, InsI, InsII, and Actb in biological triplicate
      analyses.Reproducible amplification of these mRNAs from MIN6, MIN6 B1, and Vero
      PPI cells and their CM suggests that beta cells transcribe and release these
      mRNAs into their environment. mRNAs secreted from insulin-producing cells into
      their extracellular environment may have potential as extracellular biomarkers
      for assessing beta cell mass and function.

PMID- 21898211
TI  - Microarray analysis of mRNAs: experimental design and data analysis fundamentals.
AB  - Microarray technology has made it possible to quantify gene expression of
      thousands of genes in a single experiment. With the technological advancement, it
      is now possible to quantify expression of all known genes using a single
      microarray chip. With this volume of data and the possibility of improper
      quantification of expression beyond our control, the challenge lies in
      appropriate experimental design and the data analysis.This chapter describes the
      different types of experimental design for experiments involving microarray
      analysis (with their specific advantages and disadvantages). It considers the
      optimum number of replicates for a particular type of experiment. Additionally,
      this chapter describes the fundamentals of data analysis and the data analysis
      pipeline to be followed in most common types of microarray experiment.

PMID- 21898212
TI  - Software and tools for microarray data analysis.
AB  - A typical microarray experiment results in series of images, depending on the
      experimental design and number of samples. Software analyses the images to obtain
      the intensity at each spot and quantify the expression for each transcript. This
      is followed by normalization, and then various data analysis techniques are
      applied on the data. The whole analysis pipeline requires a large number of
      software to accurately handle the massive amount of data. Fortunately, there are
      large number of freely available and commercial software to churn the massive
      amount of data to manageable sets of differentially expressed genes, functions,
      and pathways. This chapter describes the software and tools which can be used to
      analyze the gene expression data right from the image analysis to gene list,
      ontology, and pathways.

PMID- 21898213
TI  - Analysis of gene expression as relevant to cancer cells and circulating tumour
      cells.
AB  - Current literature provides significant evidence to support the concept that
      there are limited subpopulations of cells within a solid tumour that have
      increased tumour-initiating potential relative to the total tumour population.
      Such tumour-initiating cells have been identified in leukaemia and in a variety
      of solid tumours using different combinations of cell surface markers, suggesting
      that a tumour-initiating cell heterogeneity exists for each specific tumour.
      These studies have been extended to endometrial cancer; and herein we present
      several experimental approaches, both in vitro and in vivo, that can be used to
      determine whether such populations exist, and if so, to characterize them. These
      methods are adaptable to the investigation of tumour-initiating cells from other
      tumour types.

PMID- 21898214
TI  - Gene expression profiling in formalin-fixed, paraffin-embedded tissues using the
      whole-genome DASL assay.
AB  - Here, we provide a detailed technical description of a gene expression assay
      (Whole-Genome DASL (WG-DASL)), which not only enables whole-genome
      transcriptional profiling of degraded material, such as formalin-fixed, paraffin
      embedded tissues, but is also capable of generating robust profiles with low
      input intact RNA. The WG-DASL assay combines target-specific annealing,
      extension, and ligation events followed by universal PCR and labeling steps to
      generate highly multiplexed Cy3-labeled products. These short products, which are
      single-stranded, are directly hybridized to a whole-genome expression BeadChip
      (HumanRef-8) containing probe content corresponding to ~24 K RefSeq transcripts.
      After washing and imaging, fluorescence emissions are quantitatively recorded for
      each probe using high-resolution confocal scanners and imaging software.
      GenomeStudio software allows direct analysis of mRNA expression data and provides
      results in standard file formats that can be readily exported and analyzed with
      most standard gene expression analysis software programs. This technology is
      particularly useful for genome-wide expression profiling in degraded, archived
      material, including limited quantities of clinical samples, such as
      microdissected and biopsied materials.

PMID- 21898215
TI  - MicroRNA expression analysis: techniques suitable for studies of intercellular
      and extracellular microRNAs.
AB  - MicroRNAs, the class of small ribo-regulators, have been implicated in the
      regulation of a range of different biological processes, including development
      and differentiation, proliferation, and cell death. Only for a small fraction of
      identified microRNAs has a function been elucidated; therefore, a great deal of
      research remains to be performed to fully understand the role and implications of
      microRNAs.This chapter discusses protocols for the isolation of microRNAs,
      reverse transcription, PCR, and large scale profiling using TaqMan low density
      miRNA arrays for analysis of microRNA expression levels.

PMID- 21898216
TI  - Western blotting analysis as a tool to study receptor tyrosine kinases.
AB  - Receptor tyrosine kinases (RTKs) are involved in critical aspects of cell
      physiology ranging from cell -survival, proliferation, growth, migration, and
      differentiation. A tight control of the extent and duration of signals elicited
      by activated RTKs is crucial for preventing over-stimulation, which can
      ultimately lead to unrestrained proliferative ability and neoplastic growth.
      Ligand-induced downregulation of RTKs has emerged as a key negative regulatory
      mechanism that can accomplish signaling attenuation, by removing activated
      receptors from the cell surface and committing them to degradation. The ability
      of RTKs to escape from ligand-induced downregulation has been reported as a
      recurrent mechanism of oncogenic deregulation in cancer.Western blotting
      procedures have been extensively proven as straightforward assays to evaluate 
      protein expression levels and have been widely applied to study RTKs
      downregulation.

PMID- 21898217
TI  - 2D gel electrophoresis and mass spectrometry identification and analysis of
      proteins.
AB  - Analysis of the protein expression patterns in clinical samples and cells by
      proteomic technologies offers opportunities to discover potentially new
      biomarkers for early detection and diagnosis of disease. One of the most widely
      used techniques to study the proteome of a biological system is two-dimensional
      polyacrylamide gel electrophoresis (2D-PAGE). In particular, a modified version
      of 2D-PAGE, two-dimensional difference gel electrophoresis (2D-DIGE), which uses
      differential labelling of protein samples with up to three fluorescent tags,
      offers greater sensitivity and reproducibility over conventional 2D-PAGE. In this
      chapter, we will introduce methods for the analysis of whole cell lysates from
      human cancer cell lines using 2D-DIGE and identification of differentially
      expressed proteins using liquid chromatography mass spectrometry, i.e. LC-MS/MS.

PMID- 21898218
TI  - Design, construction, and analysis of cell line arrays and tissue microarrays for
      gene expression analysis.
AB  - Cell line array (CMA) and tissue microarray (TMA) technologies are high
      throughput methods for analysing both the abundance and distribution of gene
      expression in a panel of cell lines or multiple tissue specimens in an efficient
      and cost-effective manner. The process is based on Kononen's method of extracting
      a cylindrical core of paraffin-embedded donor tissue and inserting it into a
      recipient paraffin block. Donor tissue from surgically resected paraffin-embedded
      tissue blocks, frozen needle biopsies or cell line pellets can all be arrayed in
      the recipient block. The representative area of interest is identified and
      circled on a haematoxylin and eosin (H&E)-stained section of the donor block.
      Using a predesigned map showing a precise spacing pattern, a high density array
      of up to 1,000 cores of cell pellets and/or donor tissue can be embedded into the
      recipient block using a tissue arrayer from Beecher Instruments. Depending on the
      depth of the cell line/tissue removed from the donor block 100-300 consecutive
      sections can be cut from each CMA/TMA block. Sections can be stained for in situ
      detection of protein, DNA or RNA targets using immunohistochemistry (IHC),
      fluorescent in situ hybridisation (FISH) or mRNA in situ hybridisation (RNA-ISH),
      respectively. This chapter provides detailed methods for CMA/TMA design,
      construction and analysis with in-depth notes on all technical aspects including
      tips to deal with common pitfalls the user may encounter.

PMID- 21898219
TI  - Immunohistochemical and immunofluorescence procedures for protein analysis.
AB  - Immunohistochemistry (IHC) and immunofluorescence (IF) involve the binding of an
      antibody to a cellular or tissue antigen of interest and then visualisation of
      the bound product by fluorescence/with the 3,3'-diaminobenzidine (DAB) chromogen
      detection system. With increasing numbers of available antibodies against
      cellular epitopes, IHC and IF are very useful diagnostic tools as well as a means
      to guide specific therapies that target a particular antigen on cell/tissue
      samples.There are several IHC and IF staining methods that can be employed
      depending on the type of specimen under study, the degree of sensitivity
      required, and the cost considerations. The following is a basic "generic" method
      for localising proteins and other antigens by direct, indirect, IHC and IF. The
      method relies on proper fixation of tissue/cells to retain cellular distribution
      of antigen and to preserve cellular morphology. Details of reagents required are
      outlined. Consideration is also given to artefacts and other potential pitfalls
      and thus means to avoid them.

PMID- 21898220
TI  - Advanced microscopy: laser scanning confocal microscopy.
AB  - Fluorescence microscopy is an important and fundamental tool for biomedical
      research. Optical microscopy is almost non-invasive and allows highly spatially
      resolved images of organisms, cells, macromolecular complexes, and biomolecules
      to be obtained. Generally speaking, the architecture of the observed structures
      is not significantly modified and the environmental conditions can be kept very
      close to physiological reality. The development of fluorescence microscopy was
      revolutionized with the invention of laser scanning confocal microscopy (LSCM).
      With its unique three-dimensional representation and analysis capabilities, this
      technology gives us a more real view of the world.This chapter introduces the
      reader to the methodology of setting up basic experiments for use with a laser
      scanning confocal microscope. There are practical guidelines about sample
      preparation for both fixed and living specimens, as well as examples of some of
      the applications of confocal microscopy.

PMID- 21898221
TI  - Isolation of exosomes for subsequent mRNA, MicroRNA, and protein profiling.
AB  - Exosomes are nano-sized, cell membrane surrounded structures that are released
      from many cell types. These exosomes are believed to transport a range of
      molecules, including mRNAs, miRNAs, and proteins; the contents depending on their
      cell of origin. The physiological and pathological relevance of exosomes has yet
      to be fully elucidated. Exosomes have been implicated in cell-to-cell
      communication. For example, in relation to the immune system, such exosomes may
      enable exchange of antigen or major histocompatibility complex-peptide complexes
      between antigen-bearing cells and antigen-presenting cells; in cancer, they may
      contain molecules that not only have relevance as biomarkers, but may also be
      taken up and cause adverse effects on secondary cells. Furthermore, exosomes have
      been proposed as autologous delivery systems that could be exploited for
      personalised delivery of therapeutics. In order to explore the contents and
      functional relevance of exosomes from medium conditioned by culture cells or from
      other biological fluids, prior to extensive molecular profiling, they must be
      isolated and purified. Here, we describe differential centrifugation methods
      suitable for isolating exosomes from conditioned medium and from other biological
      fluids, including serum, saliva, tumour ascites, and urine. We also detail
      Western blotting and transmission electron microscopy methods suitable for basic
      assessment of their presence, size, and purity, prior to progressing to global
      mRNA, miRNA, or protein profiling.

PMID- 21898222
TI  - Atomic force microscopy and high-content analysis: two innovative technologies
      for dissecting the relationship between epithelial-mesenchymal transition-related
      morphological and structural alterations and cell mechanical properties.
AB  - Epithelial-mesenchymal transition (EMT) is a complex series of cellular
      reprogramming events culminating in striking alterations in morphology towards an
      invasive mesenchymal phenotype. Increasingly, evidence suggests that EMT exerts a
      pivotal role in pathophysiological situations including fibrosis and cancer. Core
      to these dynamical changes in cellular polarity and plasticity is discrete
      modifications in cytoskeletal structure. In particular, newly established actin
      stress fibres supplant a preceding system of highly organised cortical actin.
      Although cumulative studies have contributed to elucidation of the detailed
      signalling pathways that underpin this elaborate molecular process, there remains
      a deficiency regarding its precise contribution to cellular biomechanics. The
      advent of atomic force microscopy (AFM) and high-content analysis (HCA) provides
      two innovative technologies for dissecting the relationship between EMT-related
      morphological and structural alterations and cell mechanical properties. AFM
      permits acquisition of high resolution topographical images and detailed analysis
      of cellular viscoelasticity while HCA facilitates a comprehensive and
      perspicacious assessment of morphological changes. In combination, they offer the
      possibility of novel insights into the dynamic traits of transitioning cells.
      Herein, a detailed protocol describing AFM and HCA techniques for evaluation of
      transforming growth factor-beta1-induced EMT of alveolar epithelial cells is
      provided.

PMID- 21898223
TI  - Targeted deletion of Hsf1, 2, and 4 genes in mice.
AB  - Heat-shock transcription factors (Hsfs) regulate transcription of heat-shock
      proteins as well as other genes whose promoters contain heat-shock elements.
      There are at least five Hsfs in mammalian cells, Hsf1, Hsf2, Hsf3, Hsf4, and
      Hsfy. To understand the physiological roles of Hsf1, Hsf2, and Hsf4 in vivo, we
      generated knockout mouse lines for these factors. In this chapter, we describe
      the design of the targeting vectors, the plasmids used, and the successful
      generation of mice lacking the individual genes. We also briefly describe what we
      have learned about the physiological functions of these genes in vivo.

PMID- 21898224
TI  - The role of heat shock factors in stress-induced transcription.
AB  - Heat shock proteins (HSPs) are rapidly induced after stresses, such as heat
      shock, and accumulate at high concentrations in cells. HSP induction involves a
      family of heat shock transcription factors that bind the heat shock elements of
      the HSP genes and mediate transcription in trans. We discuss methods for the
      study of HSP binding to HSP promoters and the consequent increases in HSP gene
      expression in vitro and in vivo.

PMID- 21898226
TI  - The role of p23, Hop, immunophilins, and other co-chaperones in regulating Hsp90
      function.
AB  - Molecular chaperones are a diverse group of highly conserved proteins that
      transiently interact with partially folded polypeptide chains during normal
      cellular processes, such as protein translation, translocation, and disassembly
      of protein complexes (1). Prior to folding or after denaturation, hydrophobic
      residues that are normally sequestered within a folded protein are exposed to the
      aqueous environment and are prone to aggregation or misfolding. Multiple classes
      of molecular chaperones, such as Hsp70s and Hsp40s, recognize and transiently
      bind polypeptides with exposed hydrophobic stretches in order to prevent
      misfolding. Other types of chaperones, such as Hsp90, have more specialized
      functions in that they appear to interact with only a subset of cellular
      proteins. This chapter focuses on the role of Hsp90 and partner co-chaperones in
      promoting the folding and activation of a diverse group of proteins with critical
      roles in cellular signaling and function.

PMID- 21898225
TI  - Hsp90 and client protein maturation.
AB  - Heat-shock protein 90 (Hsp90) is a molecular chaperone that assists in the
      maturation of a limited set of substrate proteins that are collectively referred
      to as clients. The majority of identified Hsp90 clients are involved in signal
      transduction, including many steroid hormone receptors and kinases. A handful of
      Hsp90 clients can be classified as nonsignal transduction proteins, including
      telomerase, cystic fibrosis transmembrane conductance regulator, and antigenic
      peptides destined for major histocompatibility complex. Because Hsp90 clients are
      causative agents in cancer and cystic fibrosis, research on Hsp90 has intensified
      in recent years. We review the historical path of Hsp90 research within each
      class of client (kinase, hormone receptor, and nonsignal transduction clients)
      and highlight current areas of active investigation.

PMID- 21898227
TI  - Detecting HSP90 phosphorylation.
AB  - Heat-shock protein 90 (HSP90) is an essential molecular chaperone in eukaryotes.
      It is important for chaperoning proteins that are important determinants of
      multistep carcinogenesis. HSP90's ATPase activity is associated with its
      chaperone function. Co-chaperones as well as posttranslational modifications
      (phosphorylation, acetylation, and S-nitrosylation) are important for regulating
      its ATPase activity. Yeast can be used to express and purify HSP90 and also
      detect its phosphorylation by pan-phosphoserine or phosphothreonine antibodies.

PMID- 21898228
TI  - Role of molecular chaperones in biogenesis of the protein kinome.
AB  - Molecular chaperones promote polypeptide folding in cells by protecting newly
      made and otherwise misfolded proteins against aggregation or degradation by the
      ubiquitin proteasome pathway. The roles of Saccharomyces cerevisiae Cdc37 and
      Ydj1 molecular chaperones are described in this chapter. We focus on biogenesis
      of protein kinases that require several different molecular chaperones for their
      proper folding. Specific among these is Cdc37, which binds directly to its kinase
      clients either during or shortly after translation and protects them against
      rapid proteasomal degradation. Ydj1 has a similar role, but is less specific for
      protein kinases in its role as a molecular chaperone. The method that we describe
      uses pulse chase and immunoprecipitation to analyze the fate of newly made
      proteins. Two kinetically distinct pathways of degradation can be discerned using
      this methodology that is dependent on the presence of an Hsp90 inhibitor or
      occurs in mutants of the molecular chaperones under study. The first is "zero
      point" degradation that occurs either during or immediately after translation.
      The second is a slower pathway, where the half-life of kinase is approximately 20
      min after translation.

PMID- 21898229
TI  - Nucleotide exchange factors for Hsp70 chaperones.
AB  - The ATPase cycle of Hsp70 chaperones controls their transient association with
      substrate and, thus, governs their function in protein folding. Nucleotide
      exchange factors (NEFs) accelerate ADP release from Hsp70 which results in
      rebinding of ATP and release of the substrate. This chapter describes several
      methods suitable to study NEFs of Hsp70 chaperones. On the one hand, steady-state
      ATPase assays provide information on how the NEF influences progression of the
      Hsp70 through the entire ATPase cycle. On the other hand, nucleotide release can
      be measured directly using labeled nucleotides, which enables identification and
      further characterization of NEFs.

PMID- 21898230
TI  - Reconstitution of CHIP E3 ubiquitin ligase activity.
AB  - CHIP, the carboxyl-terminus of Hsp70 interacting protein, is both an E3 ubiquitin
      ligase and an Hsp70 co-chaperone and is implicated in the degradation of
      cytosolic quality control and numerous disease substrates. CHIP has been shown to
      monitor the folding status of the CFTR protein, and we have successfully
      reconstituted this activity using a recombinant CFTR fragment consisting of the
      cytosolic NBD1 and R domains. We have found that efficient ubiquitination of
      substrates requires chaperone activity to either deliver the substrate to CHIP or
      to maintain the substrate in a ubiquitination-competent conformation. This
      chaperone activity can be provided by the Hsp70/Hsp40 molecular chaperone system
      as seen in the NBD1-R ubiquitination assay. Alternatively, heat treatment of CHIP
      can activate its own innate substrate-binding activity and allow for efficient
      ubiquitination of model substrates, such as denatured luciferase. Here, we
      describe methods for purifying the recombinant proteins necessary for in vitro
      reconstitution of CHIP ubiquitin ligase activity, as well as two methods used to
      monitor CHIP ligase activity. One method allows for the measurement of the Hsp70-
      and Hsp40-dependent CHIP activity while the other measures the Hsp40- and Hsp70
      independent activity of heat-activated CHIP.

PMID- 21898231
TI  - Structure-functions of HspB1 (Hsp27).
AB  - Human HspB1 (also denoted Hsp27) is a well-known member, together with alphaB
      crystallin, of the small heat-shock (or stress) proteins (sHsps) (20-40 kDa). In
      this chapter, I describe procedures for testing the oligomeric and
      phosphorylation patterns of HspB1 as well as its interaction with specific
      partner/client polypeptides using tissue culture cells genetically modified to
      express different levels of this protein. The procedures have been developed in
      my laboratory and could be used in any well-established cellular laboratory. In
      addition, the different procedures presented here could be extended to test the
      nine other human sHsp members as well as sHsps from other species.

PMID- 21898232
TI  - Combined lentiviral and RNAi technologies for the delivery and permanent
      silencing of the hsp25 gene.
AB  - Elevated heat shock protein 27 (Hsp27) expression has been found in a number of
      tumors, including breast, prostate, gastric, uterine, ovarian, head and neck, and
      tumor arising from the nervous system and urinary system, and determined to be a
      predictor of poor clinical outcome. Although the mechanism of action of Hsp27 has
      been well documented, there are currently no available inhibitors of Hsp27 in
      clinical trials. RNA interference (RNAi) has the potential to offer more
      specificity and flexibility than traditional drugs to silence gene expression.
      Not surprisingly, RNAi has become a major focus for biotechnology and
      pharmaceutical companies, which are now in the early stages of developing RNAi
      therapeutics, mostly based on short interfering RNA (siRNAs), to target viral
      infection, cancer, hypercholesterolemia, cardiovascular disease, macular
      degeneration, and neurodegenerative diseases. However, the critical issues
      associated with RNAi as a therapeutic are delivery, specificity, and stability of
      the RNAi reagents. To date, the delivery is currently considered the biggest
      hurdle, as the introduction of siRNAs systemically into body fluids can result in
      their degradation, off-target effects, and immune detection. In this chapter, we
      discuss a method of combined lentiviral and RNAi-based technology for the
      delivery and permanent silencing of the hsp25 gene.

PMID- 21898233
TI  - Quantification of HSP27 and HSP70 molecular chaperone activities.
AB  - Stress-inducible heat-shock proteins (HSPs, like HSP70 and HSP27) are molecular
      chaperones that -protect cells from stress damage by keeping cellular proteins in
      a folding competent state and preventing them from irreversible aggregation.
      HSP27 and HSP70 chaperone activities are useful indicators to test chemical
      products and physical stress impact on protein denaturation, to select HSP
      inhibitors, or to -determine the implication of the chaperone function in other
      HSP activities, such as apoptosis. We have developed two simple and fast
      chaperone activity tests for HSP27 and HSP70 that we initially set up to test the
      effect of potential HSP inhibitors obtained after screening of chemical and small
      molecule libraries. These chaperone quantification tests are based on the
      capacity of HSP to counteract chemical or thermal protein aggregation.

PMID- 21898234
TI  - Measuring Hsp72 (HSPA1A) by indirect sandwich ELISA.
AB  - The enzyme-linked immunosorbent assay (ELISA) is an immunological technique which
      is used to determine the presence or quantity of an antigen within a sample.
      ELISAs rely on the use of at least one antibody (Ab) specific for the antigen
      being measured. This antibody is covalently linked to an enzyme which is detected
      through the use of an enzymatic substrate, which can be colorimetric,
      fluorogenic, or chemiluminescent. The ELISA for Hsp72 described here is a typical
      indirect sandwich ELISA, which can be used for measuring Hsp72 from
      cellular/tissue extracts, tissue culture supernatant, and serum. Typically, a 96
      well ELISA plate is coated with a specific antibody which captures Hsp72 from the
      sample, and another antibody specific for a different Hsp72 epitope is used to
      detect Hsp72. An enzyme-labelled species-specific antibody conjugate is then
      applied which is consequently detected using a colorimetric enzyme substrate. The
      quantity of Hsp72 present in the samples is interpolated using a standard curve
      of known amounts of pure Hsp72.

PMID- 21898235
TI  - Analysis of heat-shock protein localisation using flow cytometry.
AB  - The use of flow cytometry in heat-shock protein (HSP) research is increasing
      rapidly due to the high sensitivity and versatility of the technique. The method
      allows the simultaneous analysis of multiple proteins within numerous cell types
      in a heterogeneous sample, providing advantages over alternative techniques, such
      as ELISA and Western blotting. As a result, flow cytometry is becoming the
      leading technique used in this area of research. The current chapter describes
      the methodology for preparing samples for this technique and outlines two
      protocols for the analysis of surface- and intracellular-localised HSPs.

PMID- 21898236
TI  - Quantitation of heat-shock proteins in clinical samples using mass spectrometry.
AB  - Mass spectrometry (MS) is a powerful analytical tool for proteomics research and
      drug and biomarker discovery. MS enables identification and quantification of
      known and unknown compounds by revealing their structural and chemical
      properties. Proper sample preparation for MS-based analysis is a critical step in
      the proteomics workflow because the quality and reproducibility of sample
      extraction and preparation for downstream analysis significantly impact the
      separation and identification capabilities of mass spectrometers. The highly
      expressed proteins represent potential biomarkers that could aid in diagnosis,
      therapy, or drug development. Because the proteome is so complex, there is no one
      standard method for preparing protein samples for MS analysis. Protocols differ
      depending on the type of sample, source, experiment, and method of analysis.
      Molecular chaperones play significant roles in almost all biological functions
      due to their capacity for detecting intracellular denatured/unfolded proteins,
      initiating refolding or denaturation of such malfolded protein sequences and more
      recently for their role in the extracellular milieu as chaperokines. In this
      chapter, we describe the latest techniques for quantitating the expression of
      molecular chaperones in human clinical samples.

PMID- 21898237
TI  - Bioinformatic approach to identify chaperone pathway relationship from large
      scale interaction networks.
AB  - We describe a computational protocol to identify functional modules and pathway
      relationship of chaperones based on physical interaction data derived from high
      throughput proteomic experiments. The protocol first identifies interacting
      proteins shared by the different chaperone systems to organize the chaperones
      into functional modules. The chaperone functional modules represent groups of
      chaperones that are involved in mediating the folding of the shared interacting
      proteins. Either the chaperones in a module can function along a single folding
      pathway of a given substrate protein or the substrate protein might have two or
      more different folding pathways that the chaperones act on independently. As
      described in our computational protocol, probabilities of these pathway
      relationships between two chaperones in a two-component chaperone module can be
      determined using whole-genome expression and cellular pathways as reference. This
      protocol is potentially useful for identifying functional modules and pathway
      relationships in other biological systems that involve multiple proteins with
      many identified interactions.

PMID- 21898238
TI  - Hsp70: anti-apoptotic and tumorigenic protein.
AB  - Heat shock protein 70 (Hsp70) is a powerful chaperone whose expression is induced
      in response to a wide variety of physiological and environmental insults,
      including anticancer chemotherapy, thus allowing the cell to survive to lethal
      conditions. Hsp70 cytoprotective properties may be explained by its anti
      apoptotic function. Indeed, this protein can inhibit key effectors of the
      apoptotic machinery at the pre- and postmitochondrial level. In cancer cells, the
      expression of Hsp70 is abnormally high, and Hsp70 may participate in oncogenesis
      and in resistance to chemotherapy. In rodent models, Hsp70 overexpression
      increases tumor growth and metastatic potential. Depletion or inhibition of Hsp70
      frequently reduces the size of the tumors and even can cause their complete
      involution. But Hsp70 can also be found in the extracellular medium. Its role is
      then immunogenic and the term chaperokine to define the extracellular chaperones
      has been advanced. Hsp70 tumorigenic functions as well as the strategies that are
      being developed in cancer therapy in order to inhibit Hsp70 are commented in this
      chapter.

PMID- 21898239
TI  - Determination of cell survival or death.
AB  - Cell death (in particular, apoptosis and necrosis) is accompanied by appearance
      of certain hallmarks that are manifested as specific alterations in cellular
      membranes, cytoplasm, nucleus and mitochondria. Some of those hallmarks are
      easily detectable in situ and, therefore, they can be applied for the assessment
      of dying or dead cells. In turn, there are also signs of viable cells that
      include a set of features, such as normal functioning of their membranes and
      organelles, ability to proliferate, etc. The present chapter provides
      descriptions of several convenient methods for quantitative determination of dead
      (apoptotic and necrotic) cells and also methods for determination of survived and
      viable cells. Here, we describe in details the methods of annexin V/propidium
      iodide (PI) staining, TUNEL assay, Hoechst/PI staining, MTS tetrazolium assay,
      and colony formation assay, with the principles, advantages, and drawbacks of
      each technique.

PMID- 21898240
TI  - Immunohistochemistry of human Hsp60 in health and disease: from autoimmunity to
      cancer.
AB  - Hsp60 (also called Cpn60) is a chaperonin with essential functions for cell
      physiology and survival. Additionally, its involvement in the pathogenesis of a
      number of diseases (e.g., some autoimmune disorders and cancer) is becoming
      evident with new research. For example, the distribution and levels of Hsp60 in
      cells and tissues have been found altered in many pathologic conditions, and the
      significance of these alterations is being investigated in a number of
      laboratories. The aim of this ongoing research is to determine the meaning of
      these Hsp60 alterations with regard to pathogenetic mechanisms, diagnosis,
      classification of lesions, and assessing of prognosis and response to treatment.
      Hsp60 occurs in the mitochondria, i.e., its typical residence according to
      classic knowledge, and also in other locales, such as the cytosol, the cell
      membrane, the intercellular space, and biological fluids (e.g., blood and
      cerebrospinal fluid). Detection and quantitative determinations in all these
      locations are becoming essential components of laboratory pathology in clinics
      and research. Consequently, immunohistochemistry targeting Hsp60 is also becoming
      essential for pathologists and researchers interested in disorders involving this
      chaperonin. In this chapter, we briefly summarize some recent discoveries on the
      participation of Hsp60 in the pathogenesis of human diseases and describe in
      detail how to perform immunohistochemical reactions for detecting the chaperonin,
      determining its location, and measuring its levels of expression.

PMID- 21898241
TI  - Preparation of a heat-shock protein 70-based vaccine from DC-tumor fusion cells.
AB  - We have developed an enhanced molecular chaperone-based vaccine through rapid
      isolation of heat-shock protein 70 peptide complexes (Hsp70.PC) after the fusion
      of tumor and dendritic cells (DCs) (Hsp70.PC-F). In this approach, the tumor
      antigens are introduced into the antigen-processing machinery of dendritic cells
      through the cell fusion process and, thus, we can obtain antigenic tumor peptides
      or their intermediates that have been processed by dendritic cells. Our results
      show that Hsp70.PC-F has increased immunogenicity compared to preparations from
      tumor cells alone and, therefore, constitutes an improved formulation of
      chaperone protein-based tumor vaccine.

PMID- 21898242
TI  - Isolation of heat shock protein complexes.
AB  - Heat shock proteins (Hsp) are molecular chaperones with the capability to
      interact with a wide range of other proteins and are thus often found coupled
      with other heat shock and non-heat shock proteins. This can be an advantage to
      study specific interactions between a chaperone and other proteins and to
      generate an antitumoral immune response. In this chapter, we present two
      protocols to isolate Hsp. One involves column chromatography with hydroxyapatite
      and the other employs immunoprecipitation with antibodies coupled to magnetic
      beads. In both cases, we specifically want to isolate Hsp coupled with other
      proteins and use the Hsp complexes as intermediaries to present the coupled
      peptides/proteins to the immune system, or to explore the associations of a
      particular Hsp with other proteins.

PMID- 21898243
TI  - Enhancing antigen cross-presentation and T-cell priming by complexing protein
      antigen to recombinant large heat-shock protein.
AB  - Large heat-shock proteins (HSPs), including hsp110 and grp170, are unique
      immunochaperones capable of carrying and introducing antigens into professional
      antigen-presenting cells for efficient cross-presentation. Therefore,
      reconstituted chaperone complexes of large HSPs and protein antigen may be
      exploited for augmentation of an antigen-specific immune response. The methods
      for the preparation of the recombinant protein antigen chaperone complex and
      characterization of its T-cell priming capability in both in vitro and in vivo
      settings are described.

PMID- 21898245
TI  - Analysis of cellular migration using a two-chamber methodology.
AB  - Directed cell migration is fundamental to both physiological and
      pathophysiological processes such as embryogenesis, wound healing, and cancer
      metastasis. A complex series of events are required for directional cell
      migration, which is initiated by a migration-promoting or chemotactic stimulus,
      resulting in cellular polarization and entry into a cyclical pattern of leading
      edge protrusion, adhesion, and retraction of the trailing edge allowing cell
      movement. Heat shock proteins such as Hsp27, Hsp90, alphaB-crystallin, as well as
      heat shock transcription factors, are important players in both physiological and
      pathophysiological cell migration. A variety of techniques are currently
      available to assess cell migration, and among the most commonly utilized are
      those that employ a two-chamber methodology, such as that developed by Stephen
      Boyden in the early 1960s. Herein, we describe the use of a multiwell
      microchemotaxis migration assay that has the advantages of being reusable,
      inexpensive, highly reproducible, and requiring only a small volume of reagents.

PMID- 21898244
TI  - Investigating receptors for extracellular heat shock proteins.
AB  - Extracellular heat shock proteins (HSP) play important roles in cell signaling
      and immunity. Many of these effects are mediated by cell surface receptors
      expressed on a wide range of cell types. We have investigated the nature of such
      proteins by cloning candidate receptors into cells (CHO-K1) with the rare
      property of being null for HSP binding. Using this approach, we have discovered
      that Hsp70 binds to a least two classes of receptor: c-type lectin receptors
      (CLR) and scavenger receptors (SR). However, the nature of the receptor-ligand
      interactions is not yet clear. Hsp70 can bind to LOX-1 (a member of both the CLR
      and SR), with the c-type lectin binding domain (CTLD) as well as the SR family
      members SREC-I and FEEL-1/CLEVER-1/STABILIN-1, which by contrast have arrays of
      EGF-like repeats in their extracellular domains. In this chapter, we discuss (1)
      methods for determining HSP receptors, (2) approaches to study of individual
      receptors in cells that contain multiple such receptors, and (3) methods for
      investigating HSP receptor function in vivo.

PMID- 21898246
TI  - Challenges facing the forest industry in relation to seed dormancy and seed
      quality.
AB  - Artificial regeneration of forests through planting requires high quantities of
      quality seeds for growing vigorous seedlings. These seedlings are raised in
      nurseries, where germination capacity (GC) and speed are the most important
      germination parameters. Germination performance is enhanced by prescribing
      species-specific dormancy-breaking treatments to individual seedlots in bare-root
      and container nurseries. For most conifer species in British Columbia, the
      dormancy-breaking treatments and germination conditions have been worked out, but
      fine-tuning and optimization could improve germination capacity and speed of
      germination. Implications of inter- and intra-species variations in germination
      behaviour and seed quality and their influence on the development of
      unintentional directional selection of specific genotypes are discussed. The
      potential of molecular and genomics approaches to understand the underlying
      biology of seed germination-related problems is also discussed.

PMID- 21898247
TI  - Challenges facing seed banks and agriculture in relation to seed quality.
AB  - Seeds form a convenient vehicle for storage of germplasm, both for agricultural
      purposes and conservation of wild species. When required, seeds can be taken from
      storage and germinated, and plants can be propagated for the desired purpose,
      e.g., crop production or biome restoration. However, seed dormancy often
      interferes with stand establishment or industrial utilization in crops and
      germination of wild species. An anticipated termination of dormancy (i.e., before
      crop harvest) also occurs, with preharvest sprouting as a consequence. In order
      to overcome these problems, a better understanding of dormancy is required. This
      chapter is devoted to discuss the achievement of such understanding in
      problematic species.

PMID- 21898248
TI  - Standardizing seed dormancy research.
AB  - Seeds are very attractive and convenient for molecular genetic studies that
      challenge principal biological phenomena related to the initiation and
      suppression of growth (e.g., germination and dormancy, respectively). The number
      of reports in this field is rapidly expanding. Seed dormancy is a widely
      misinterpreted biological attribute. One of the main reasons is the general
      neglect of reliable dormancy assays; often, the sole criterion of current
      dormancy assays is the total germination of a seed population after a defined
      period of time. This is a very insensitive and inaccurate method, particularly
      when comparing dormancy levels of seeds from different genotypes, seeds subjected
      to different treatments, or seeds originating from different environments. Other
      seed parameters are far more useful. Furthermore, before undertaking
      comprehensive molecular and biochemical studies to elucidate the underlying
      mechanisms of dormancy of a given species, it is pivotal to determine the general
      types or categories of dormancy that are imposed and whether these are influenced
      by the external environment. Research strategies should be adjusted to this. In
      order to distinguish dead from dormant seeds, a viability test should be
      developed. This chapter addresses in a very general way these pitfalls in
      dormancy research with a focus on current plant model systems in molecular
      genetics, such as Arabidopsis thaliana and Medicago truncatula.

PMID- 21898249
TI  - Eyeing emergence: modified treatments for terminating dormancy of conifer seeds.
AB  - Many seeds of coniferous species display a deep primary dormancy at maturity and
      require several weeks of pretreatment to produce seed populations that germinate
      in a vigorous and timely manner. Facilitating an efficient transition from
      dormancy to germination by devising improved protocols for dormancy breakage is
      not only important to conifer seed research, aiding in the study of the dormancy
      process itself, but is also of interest and applicability to commercial forest
      nursery operations. In the forests of British Columbia, Canada, several conifer
      species are well-adapted to their environment, with seeds needing to experience
      long durations in the moist state at cool or fluctuating temperatures. These
      include yellow-cedar (Callitropsis nootkatensis), western white pine (Pinus
      monticola), and true fir species, such as Pacific silver fir and subalpine fir
      (Abies amabilis and A. lasiocarpa, respectively). In this chapter, we discuss the
      development of new dormancy-breaking protocols for the aforementioned species
      that centre on the balance of several key aspects: (1) reducing the time needed
      to terminate dormancy in the seed population; (2) synchronicity of germination;
      (3) ease of use; (4) cost-effectiveness; and (5) repeatability. Where possible,
      any new or modified protocol should be further tested in relationship to
      promoting rapid seedling growth in a forest nursery greenhouse setting and after
      planting at natural stands. Based on the five criteria listed above, very
      significant improvements compared to traditional dormancy-breaking methods have
      been achieved for the targeted conifer species. Where tested (e.g. yellow-cedar),
      the modified dormancy-breaking treatments result in vigorous growth in the
      greenhouse and after planting at natural stands.

PMID- 21898250
TI  - Production of seed samples for the effective molecular analysis of dormancy
      cycling in Arabidopsis.
AB  - Most often, the samples used for molecular analysis of dormancy are populations
      of seeds. An essential survival characteristic of seed populations inhabiting the
      variable surface layers of the soil is that individuals in the population do not
      behave uniformly. In addition, seed dormancy (SD) status of the whole population
      constantly changes even in the dry state. For these and other reasons, production
      of appropriate and adequately characterized seed samples is the key to the
      correct and most informative interpretation of molecular studies. This is
      particularly important when the aim is to describe and explain seed behaviour in
      the natural environment. Molecular studies of seed dormancy, and especially
      ecologically relevant behaviour, such as dormancy cycling, should therefore
      involve characterization of dormancy status based on a sound understanding of
      seed physiology. This chapter discusses the problems and pitfalls of using
      Arabidopsis and provides protocols devised for use with the Arabidopsis ecotype
      Cape Verde Islands for the production and characterization of samples to be used
      in molecular analysis of dormancy transitions and cycling.

PMID- 21898251
TI  - Approaches to the identification of ABAR as an abscisic acid receptor.
AB  - Abscisic acid (ABA) is a vital phytohormone that regulates seed maturation and
      germination, seedling growth, and adaptation to environmental stresses. ABA
      functions through a complex network of signaling pathways, where the cell
      response is initiated by an ABA receptor which triggers downstream signaling
      cascades to induce the final physiological effects. Two classes of technologies
      may be used for the isolation of ABA receptors. One is the genetic screening for
      ABA receptor mutants, and another is the biochemical isolation of ABA-binding
      proteins that are putative ABA receptors. We implemented biochemical approaches,
      namely, the purification of ABA-binding proteins to identify a putative ABA
      receptor; this protein was further characterized by a combination of biochemical
      and reverse genetic approaches. The identified ABA receptor, called ABAR,
      mediates the responses of plants to ABA in seed germination, postgerminative
      growth, and stomatal movement. This protein is the H subunit (CHLH) of the
      magnesium protoporphyrin-IX chelatase (Mg-chelatase) that also plays a key role
      in both chlorophyll biosynthesis and plastid-to-nucleus signaling. Here, we
      describe the experimental procedures for the purification of ABA-binding proteins
      and the identification of the ABA-binding protein, ABAR/CHLH, as an ABA receptor.

PMID- 21898252
TI  - Profiling of hormones and related metabolites in seed dormancy and germination
      studies.
AB  - Seed dormancy and germination are regulated by several plant hormones, such as
      abscisic acid, gibberellin, auxin (indole-3-acetic acid), ethylene, and
      brassinosteroid. Endogenous concentrations of a hormone are determined by the
      balance between biosynthesis and deactivation, and contribute to the regulation
      of physiological responses. Therefore, profiling of all hormones and their
      metabolites (hormonome) is a powerful approach to elucidate the regulatory
      networks of hormone metabolism. The methods involved in the use of liquid
      chromatography-electrospray ionization-tandem mass spectrometry to develop a high
      sensitive and high-throughput hormonome platform are described in this chapter.

PMID- 21898253
TI  - In vitro assay for ABA 8'-hydroxylase: implications for improved assays for
      cytochrome P450 enzymes.
AB  - In vitro assays for cytochrome P450 enzymes developed from plant-derived
      microsomal extracts have not been used extensively for the characterization and
      quantification of enzyme activities in plant tissues. We describe here an in
      vitro assay for abscisic acid (ABA) 8'-hydroxylase that was developed using
      microsomes extracted from (+)-ABA-induced corn suspension cultures. This assay
      may be useful for further characterization and monitoring of ABA 8'-hydroxylase
      activities in germinating seeds, seedlings, and other tissues. Additionally, the
      optimization protocols provided here may be adapted towards improving in vitro
      enzyme assays for other cytochrome P450 enzymes expressed in plants.

PMID- 21898254
TI  - Functional analysis of abscisic acid 8'-hydroxylase.
AB  - Abscisic acid (ABA) plays an important role in the control of seed dormancy and
      germination. Identification of hormone metabolism genes from a particular plant
      species of interest is an essential step in hormone research. The function of
      these gene products is validated by biochemical analysis using heterologous
      expression systems, such as E. coli and yeast. ABA 8'-hydroxylase is a subfamily
      of P450 monooxygenases and is encoded by CYP707A genes. CYP707A catalyzes the
      committed step in the major ABA catabolic pathway. In this chapter, we describe
      the methods for RNA extraction from seeds, cloning the CYP707A cDNAs, protein
      expression in yeast, and biochemical analysis of their gene products.

PMID- 21898255
TI  - Isolation of genetic material from Arabidopsis seeds.
AB  - Here, we describe a series of methods suitable for the reproducible and abundant
      isolation of total RNA, genomic DNA, and total protein from dry or imbibed
      Arabidopsis seeds. The resulting material is suitable for most standard molecular
      biology procedures.

PMID- 21898256
TI  - Identification and characterization of quantitative trait loci that control seed
      dormancy in Arabidopsis.
AB  - Seed dormancy is a trait that is under multigenic control and affected strongly
      by environmental factors. Thus, seed dormancy is a typical quantitative trait.
      Natural accessions of Arabidopsis thaliana exhibit a great deal of genetic
      variation for seed dormancy. This natural variation can be used to identify genes
      controlling this trait by means of quantitative trait loci (QTL) mapping. In this
      chapter, we describe how QTL mapping for seed dormancy in Arabidopsis thaliana
      can be performed and how QTL analyses can be used to eventually identify the
      causal gene. Methods and recourses available specifically for Arabidopsis are
      described or referred to.

PMID- 21898257
TI  - Identification of seed dormancy mutants by activation tagging.
AB  - Activation tagging is an important tool for gene discovery in plants. This method
      utilizes a T-DNA sequence that contains four tandem copies of the cauliflower
      mosaic virus 35S enhancer sequence or promoters oriented outward to the T-DNA
      border sequences. These elements enhance the expression of genes neighboring on
      either side of the randomly integrated T-DNA, resulting in gain-of-function
      phenotypes. Activation tagging has identified a number of genes, including those
      fundamental to plant development, such as the floral inducer gene, FLOWERING
      LOCUS T  (FT  ). The methods surrounding activation-tagging approaches are
      described in this chapter. While seeds have generally not been the targets of
      these methods in the past, activation tagging provides a powerful approach to
      uncover genes involved in seed dormancy and germination, including those that
      mediate hormone signal transduction.

PMID- 21898258
TI  - Isolation of microRNAs that regulate seed dormancy and germination.
AB  - MicroRNAs (miRNAs) play an important role in gene regulation in many plant
      tissues and organs during various developmental stages. Previous studies have
      suggested the importance of gene regulation by miRNA in seeds. Characterizing the
      expression of miRNAs and their target genes in dormant and germinating seeds
      helps to gain a better understanding of the regulatory role of miRNAs during seed
      dormancy and germination. This can be achieved by implementing a simple miRNA
      extraction method using fractionation with isopropanol and Northern blot analysis
      using nonradioactive miRNA probes. Functional analysis of miRNA target genes
      potentially associated with seed dormancy and germination can be examined using
      mutant seeds in which specific miRNAs are deregulated by introducing silent
      mutations in the miRNA target sites of these genes.

PMID- 21898259
TI  - Proteomics and posttranslational proteomics of seed dormancy and germination.
AB  - The seed is the dispersal unit of plants and must survive the vagaries of the
      environment. It is the object of intense genetic and genomic studies because
      processes related to seed quality affect crop yield and the seed itself provides
      food for humans and animals. Presently, the general aim of postgenomics analyses
      is to understand the complex biochemical and molecular processes underlying seed
      quality, longevity, dormancy, and vigor. Due to advances in functional genomics,
      the recent past years have seen a tremendous progress in our understanding of
      several aspects of seed development and germination. Here, we describe the
      proteomics protocols (from protein extraction to mass spectrometry) that can be
      used to investigate several aspects of seed physiology, including germination and
      its hormonal regulation, dormancy release, and seed longevity. These techniques
      can be applied to the study of both model plants (such as Arabidopsis) and crops.

PMID- 21898260
TI  - Chromatin dynamics during seed dormancy.
AB  - The chromatin structure determines gene expression and thereby regulates
      developmental processes in the plant. The molecular mechanisms regulating the
      induction and release of seed dormancy are still largely unknown and the
      underlying changes in chromatin organization have hardly been analyzed. Most
      chromatin studies in plants have been performed on vegetative tissues and have
      focused on seedlings. The composition of seeds hampers molecular analyses and
      requires adaptation of the methods that are used for other tissues. Here, we give
      an overview of the current methods that are used to study different aspects of
      chromatin organization in seeds. Cytogenetic methods, like fluorescence in situ
      hybridization and immunolocalization, are used to study chromatin at the
      microscopic level. Changes in DNA methylation and histone modifications can be
      studied with molecular methods, like bisulfite sequencing, immunoblotting, and
      chromatin immunoprecipitation.

PMID- 21898261
TI  - Emerging mass spectrometry-based technologies for analyses of chromatin changes:
      analysis of histones and histone modifications.
AB  - Mass spectrometry (MS) is rapidly becoming an indispensable tool for the analysis
      of posttranslational modifications (PTMs) of proteins, and particularly histone
      PTMs that regulate physiological processes. The more traditional bottom-up
      approach of searching for modifications on peptides rather than intact proteins
      (top-down) has proven useful for finding phosphorylation, acetylation, and
      ubiquitination sites. With the use of modern instrumentation and various MS-based
      techniques, peptides and their PTMs can be characterized in a high-throughput
      manner while still maintaining high sensitivity and specificity. In complement to
      bottom-up MS, recent advances in MS technology, such as high-field Fourier
      transform ion cyclotron resonance (FTICR)-mass spectrometry, have permitted the
      study of intact proteins and their modifications. On-line and off-line protein
      separation instruments coupled to FTICR-MS allow the characterization of PTMs
      previously undetectable with bottom-up approaches. The use of unique
      fragmentation techniques in FTICR-MS provides a viable option for the study of
      labile modifications. In this chapter, we provide a detailed description of the
      analytical tools - mass spectrometry in particular - that are used to
      characterize modifications on peptides and proteins. We also examine the
      applicability of these mass spectrometric techniques to the study of PTMs on
      histones via both the bottom-up and top-down proteomics approaches.

PMID- 21898262
TI  - In vivo nuclear magnetic resonance metabolite profiling in plant seeds.
AB  - Nuclear magnetic resonance (NMR) spectroscopy has been successfully applied to
      profile a variety of primary and secondary metabolites in whole intact plant
      seeds in vivo. The nondestructive nature of NMR spectroscopy allows direct
      metabolic studies to be performed on the same seed throughout a given physio
      logical process or key lifecycle transition, such as dormancy breakage,
      germination, and early postgerminative growth. Multinuclear NMR is capable of
      evaluating seed quality by assessing nondestructively nutrient reserves and seed
      protectants at seed maturity and to further monitor reserve mobilization
      following germination, which is critical for seedling emergence. In this chapter,
      we illustrate the use of several in vivo NMR techniques for metabolite profiling
      in seeds. Importantly, some of these methods have potential for the screening of
      single seeds or seed populations to identify seedlots with compromised viability
      either due to developmental problems or as a result of deterioration during
      prolonged storage.

PMID- 21898263
TI  - In vivo 1H-NMR microimaging during seed imbibition, germination, and early
      growth.
AB  - Magnetic resonance imaging (MRI) is a superior noninvasive diagnostic tool widely
      used in clinical medicine, with more than 60 million MRI tests performed each
      year worldwide. More specialized high-resolution MRI systems capable of a
      resolution that is 100-1,000 times higher than standard MRI instruments are used
      primarily in materials science, but are used with increasing frequency in plant
      physiology. We have shown that high-resolution (1)H-nuclear magnetic resonance
      (NMR) microimaging can provide a wealth of information about the internal anatomy
      of plant seeds as small as 1 mm or even smaller. This chapter covers the methods
      associated with these imaging techniques in detail. We also discuss the
      application of (1)H-NMR microimaging to study in vivo seed imbibition,
      germination, and early seedling growth.

PMID- 21898264
TI  - Tissue-printing methods for localization of RNA and proteins that control seed
      dormancy and germination.
AB  - A number of genes and proteins are expressed in a tissue- or cell layer-specific
      manner. Spatial patterns of gene expression are critical to understanding gene
      function. Tissue printing provides a simple and rapid method to analyze
      localization of mRNA and protein at the tissue and cellular levels. This is
      especially convenient for gene expression analysis in hard tissues, such as seeds
      that are often difficult to section. Seed RNA or protein can be transferred onto
      a suitable membrane by printing the cut surface of a bisected seed. This method
      has been used successfully to determine mRNA and protein localization in seed
      research. The resolution of printed seed images and RNA and protein signals in
      tissue printing is sufficient to identify embryo- or endosperm-specific
      expression of various genes and proteins. In some cases, these studies have
      contributed to elucidating the spatial characteristics of hydrolytic enzymes
      putatively involved in the completion of germination and/or early postgerminative
      growth. By the same principle, tissue-printing methods could also be valuable for
      elucidating the spatial characteristics of genes/proteins that control the
      inception, maintenance, and termination of seed dormancy.

PMID- 21898265
TI  - Analyses of reactive oxygen species and antioxidants in relation to seed
      longevity and germination.
AB  - Evidence is emerging that reactive oxygen species (ROS) and antioxidants,
      together with plant hormones and other reactive species, such as reactive
      nitrogen species, are part of signalling networks pertinent to plant stress
      responses, cell division, and cell death. Consequently, they play pivotal roles
      in the regulation of seed development and maturation, germination and dormancy,
      seedling establishment, and seed ageing. Importantly, ROS, although essentially
      required at low concentrations, must be kept under stringent control by
      antioxidants. If the balance between pro- and antioxidative processes is lost and
      ROS production prevails, oxidative stress is the result, which can induce cell
      death and ultimately seed death. This chapter offers a variety of protocols for
      the determination of ROS, antioxidants, and stress markers aimed at enabling the
      reader to quantify these compounds. Protocols are also described to visualize ROS
      and localize the sites of ROS production, hoping to stimulate more research into
      ROS signalling and antioxidant control in key physiological and biochemical
      processes in seeds.

PMID- 21898266
TI  - Protein damage and repair controlling seed vigor and longevity.
AB  - The formation of abnormal isoaspartyl residues derived from aspartyl or
      asparaginyl residues is a major source of spontaneous protein misfolding in
      cells. The repair enzyme protein L: -isoaspartyl methyltransferase (PIMT)
      counteracts such damage by catalyzing the conversion of abnormal isoaspartyl
      residues to their normal aspartyl forms. Thus, this enzyme contributes to the
      survival of many organisms, including plants. Analysis of the accumulation of
      isoaspartyl-containing proteins and its modulation by the PIMT repair pathway,
      using germination tests, immunodetection, enzymatic assays, and HPLC analysis,
      gives new insights in understanding controlling mechanisms of seed longevity and
      vigor.

PMID- 21898267
TI  - Nitric oxide methods in seed biology.
AB  - The ubiquitous signaling molecule nitric oxide (NO) plays an important role in
      seed biology. Experiments with this biologically important gas require special
      provisions because NO in aerobic environments is readily converted into other
      oxides of nitrogen. In this chapter, we describe methods for the application of
      NO as a gas, and through the use of NO-donor compounds. We included information
      on the removal or reduction of NO with NO scavengers. Methods for detecting NO
      using NO-reactive fluorescent probes, and an apparatus incorporating an oxidizer
      column are also described.

PMID- 21898268
TI  - Seed bioinformatics.
AB  - Analysis of gene expression data sets is a potent tool for gene function
      prediction, cis-element discovery, and hypothesis generation for the model plant
      Arabidopsis thaliana, and more recently for other agriculturally relevant
      species. In the case of Arabidopsis thaliana, experiments conducted by individual
      researchers to document its transcriptome have led to large numbers of data sets
      being made publicly available for data mining by the so-called "electronic
      northerns," co-expression analysis and other methods. Given that approximately
      50% of the genes in Arabidopsis have no function ascribed to them by
      "conventional" homology searches, and that only around 10% of the genes have had
      their function experimentally determined in the laboratory, these analyses can
      accelerate the identification of potential gene function at the click of a mouse.
      This chapter covers the use of bioinformatic data mining tools available at the
      Bio-Array Resource ( http://www.bar.utoronto.ca ) and elsewhere for hypothesis
      generation in the context of seed biology.

PMID- 21898269
TI  - Anti-inflammation effects of corn silk in a rat model of carrageenin-induced
      pleurisy.
AB  - Pleurisy is an inflammation of the pleural layers that surround the lungs.
      Despite much research into inflammatory diseases, no drugs with favorable safety
      profiles are available yet for their treatment. Corn silk has been used in many
      parts of the world for the treatment of edema, cystitis, gout, kidney stones
      nephritis, and prostitutes. However, no scientific reports on the anti
      inflammatory effects of corn silk were so far available. To test the anti
      inflammatory efficacy of corn silk extract (CSEX) in a rat model of carrageenin
      (Cg)-induced pleurisy, exudate formation, and cellular infiltration, tumor
      necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1beta), vascular
      endothelial growth factor alpha (VEGF-alpha), interleukin-17 (IL-17), C3 and C4
      complement protein levels, adhesion molecule (ICAM-1) and inducible nitric oxide
      synthase (iNOS) levels, nuclear factor kappa B (NF-kappaB) activation, and total
      antioxidant activity were studied, respectively. Pretreatment with CSEX reduced
      Cg-induced pleurisy exudate, number of leukocytes, oxidative stress, C3 protein
      level, and O (2)(-) levels at the inflammatory site. Pretreatment with CSEX also
      inhibited TNF-alpha, IL-1beta, VEGF-alpha, and IL-17A and blocked inflammation
      related events (ICAM-1 and iNOS) by activation of NF-kappaB. Supplementation with
      CSEX may be a promising treatment for inflammatory diseases that involve
      oxidative stress.

PMID- 21898270
TI  - IL-33 is induced by amyloid-beta stimulation and regulates inflammatory cytokine
      production in retinal pigment epithelium cells.
AB  - Age-related macular degeneration (AMD) is the predominant cause of irreversible
      blindness in the elderly population. Despite intensive basic and clinical
      research, its pathogenesis remains unclear. However, evidence suggests that
      immunological and inflammatory factors contribute to the pathogenesis of AMD. A
      newly identified cytokine, IL-33, appears to be an important pro-inflammatory
      cytokine promoting tissue inflammation. In this study, IL-33 was increased
      through amyloid-beta(1-40) (Abeta(1-40)) stimulation and regulated inflammatory
      cytokines including IL-6, IL-8, IL-1beta, and TNF-alpha secretion using different
      signaling pathways in retinal pigment epithelium (RPE) cells. Furthermore, ST2L,
      the important component of the IL-33 receptor, was significantly increased
      following recombinant human IL-33 stimulation in RPE cells. These findings
      suggest that IL-33-mediated inflammatory responses in RPE cells are involved in
      the pathogenesis of AMD. Greater understanding of the inflammatory effect of IL
      33 and its role in RPE cells should aid the development of future clinical
      therapeutics and enable novel pharmacological approaches towards the prevention
      of AMD.

PMID- 21898271
TI  - Assessment of the influence of field size on maize gene flow using SSR analysis.
AB  - One of the factors that may influence the rate of cross-fertilization is the
      relative size of the pollen donor and receptor fields. We designed a spatial
      distribution with four varieties of genetically-modified (GM) yellow maize to
      generate different sized fields while maintaining a constant distance to
      neighbouring fields of conventional white kernel maize. Samples of cross
      fertilized, yellow kernels in white cobs were collected from all of the adjacent
      fields at different distances. A special series of samples was collected at
      distances of 0, 2, 5, 10, 20, 40, 80 and 120 m following a transect traced in the
      dominant down-wind direction in order to identify the origin of the pollen
      through SSR analysis. The size of the receptor fields should be taken into
      account, especially when they extend in the same direction than the GM pollen
      flow is coming. From collected data, we then validated a function that takes into
      account the gene flow found in the field border and that is very useful for
      estimating the % of GM that can be found in any point of the field. It also
      serves to predict the total GM content of the field due to cross fertilization.
      Using SSR analysis to identify the origin of pollen showed that while changes in
      the size of the donor field clearly influence the percentage of GMO detected,
      this effect is moderate. This study demonstrates that doubling the donor field
      size resulted in an approximate increase of GM content in the receptor field of
      7%. This indicates that variations in the size of the donor field have a smaller
      influence on GM content than variations in the size of the receptor field.

PMID- 21898272
TI  - [250 years "Inventum novum": Leopold Auenbrugger].

PMID- 21898273
TI  - [Current value of endobronchial ultrasound (EBUS)].

PMID- 21898274
TI  - [Tuberculosis in 22 Au-pairs in Germany and Austria - rapid diagnosis reduces
      risk of infection for host families].
AB  - BACKGROUND AND OBJECTIVES: The aim of this study was to investigate tuberculosis
      (TB) in au-pairs in Germany and Austria and to assess the risk of infection for
      the host families. METHODS: Reports from local health authorities were obtained
      between 2002 and 2010 (Bavaria, 12 cases) and from 2006 to 2010 (Baden
      Wuerttemberg 6, North Rhine-Westphalia and Hesse, 1 each, additionally 2 from
      Austria). RESULTS: 22 cases of tuberculosis were reported to the local health
      authorities, all of them concerning young female au-pairs, age 19 - 27 years.
      Countries of origin were: Kenya (9), Georgia (4), Mongolia (3), Indonesia (2),
      Nepal, Russia, Romania, and Peru (1 each). In 17 au-pairs, sputum-smear positive
      pulmonary tuberculosis was diagnosed. Three au-pairs presented with
      extrapulmonary tuberculosis without or only with minor pulmonary involvement. In
      two asymptomatic cases, sputum-smear negative tuberculosis was diagnosed by
      screening. The time between entry and the beginning of symptoms was 7.5 +/- 5.8
      months (0 - 19.3). 10.0 +/- 6.1 weeks (range 3 - 20 weeks) elapsed between the
      first symptoms and the diagnosis. No infection of the host families was caused by
      5 au-pairs who had no or only minor pulmonary involvement. In 17 au-pairs with
      high mycobacterial burden, the infection rate increased with the duration of time
      between symptoms and diagnosis (1 - 11 infections per au-pair). A total of 46
      contacts (21 children, 25 adults) were infected. 17 children received
      chemoprophylaxis with isoniazid (INH); none of them developed active disease. One
      child out of four who did not get INH was diagnosed with pulmonary TB. In
      addition, 5 out of 24 adults without chemoprevention developed active TB. 4 TB
      strains were drug-resistant strains, one of them multidrug-resistant.
      CONCLUSIONS: In au-pairs from countries with high burden of tuberculosis, long
      lasting cough and weariness should prompt diagnostics for tuberculosis. By
      screening, the disease can be detected before it gets infectious. If infection
      has occurred, chemoprevention with INH for nine months can prevent overt
      tuberculosis.

PMID- 21898275
TI  - [Autoimmune pancreatitis associated with rheumatoid arthritis: successful
      combination therapy with steroids and methotrexate].
AB  - MEDICAL HISTORY AND CLINICAL FINDINGS: A 70-year-old female patient suffered from
      steatorrhea and upper abdominal discomfort for 8 weeks combined with new onset of
      arthralgia in both hands. Additionally she reported elevated fasting blood
      glucose levels. The physical examination was without pathological findings except
      for mild upper abdominal pressure pain. INVESTIGATIONS: Imaging studies,
      including MRI and ultrasound examinations showed diffuse pancreatic enlargement
      without peripancreatic vessel involvement. Serological examinations showed
      elevated Cancer Associated Antigen 19 - 9 (1289 U/ml) and hyperglobulinemia with
      an IgG level of 170 mg/dl. The inflammatory markers were within normal ranges
      other than a slightly elevated erythrocyte sedimentation rate (35mm/1 h).
      Subsequent pancreatic biopsy showed lymphoplasmocellular, neutrophile and
      eosinophile granulocyte infiltration causing damage of the acinar pancreatic
      cells, typical for autoimmune pancreatitis (AIP). Magnetic resonance imaging
      (MRI) confirmed arthritis of both hands. TREATMENT AND COURSE: Medical treatment
      was started with oral prednisolone (50 mg/day) for one week, tapered to 25 mg/day
      for another 2 weeks, followed by dose reductions of 5 mg/day every 2 weeks with a
      final maintenance dose of 5 mg/day for 8 months. After the first week of steroid
      therapy methotrexate (MTX) was started with an initial dose of 10 mg/week. Dose
      was raised until a final dosage of 30 mg/week. After 8 months without relapse,
      the maintenance therapy was reduced to 20 mg/week MTX and corticosteroids were
      stopped. CONCLUSION: With this treatment regimen the patient has showed complete
      remission of AIP and arthritis for 36 months. MTX may be successful as an initial
      basic treatment to reach better control of autoimmune-related extrapancreatic
      manifestations.

PMID- 21898276
TI  - [79-year-old patient with dyspnoea and blue skin colour].

PMID- 21898277
TI  - [Chronic obstructive pulmonary disease: pathophysiology, diagnosis, and therapy].
AB  - Chronic obstructive pulmonary disease (COPD), a complex disease triggered mostly
      by exposure to cigarette smoke, is a leading cause of morbidity and mortality
      worldwide, leading not only to pulmonary damage but also to systemic impairment.
      There is growing awareness of systemic inflammation and cardiovascular,
      neurologic, psychiatric, and endocrine comorbidities associated with COPD. The
      diagnosis of CODP is based upon the clinical presentation, measurement of the
      pulmonary function, investigation of comorbidities and exclusion of differential
      diagnoses. COPD is a heterogeneous disease including various phenotypes. A number
      of drugs reduce or alleviate symptoms, increase exercise capacity, or reduce the
      number and severity of exacerbations. Non-pharmacologic measures such as smoking
      cessation, nutritional support, long term oxygen therapy, physiotherapy,
      rehabilitation, lung volume reduction and lung transplantation may be available
      for appropriate patients and can improve health status.

PMID- 21898278
TI  - [The model organism zebrafish in biomedical research: applications and
      perspectives in vascular biology and medicine].

PMID- 21898279
TI  - [New concepts for varicolele treatment in male infertility: the current
      situation].
AB  - There is no question that therapy for a varicocele in cases of male infertility
      improves the ejaculate quality. New data provide hints for an additional
      influence on the pregnancy rates in infertile partnerships.

PMID- 21898280
TI  - [Validation of a pelvic floor questionnaire with improvement and satisfaction
      scales to assess symptom severity, bothersomeness and quality of life before and
      after pelvic floor therapy].
AB  - BACKGROUND: The aim of this study was to integrate and validate an additional
      post-treatment module including improvement and satisfaction scales to the
      validated German pelvic floor questionnaire. METHODS: The questionnaire contained
      the domains bladder, bowel prolapse, and sexual symptoms. It was completed by 55
      patients before and after specific pelvic floor rehabilitation. A post-therapy
      module with improvement and satisfaction scales was integrated and tested
      psychometrically. RESULTS: Missing data did not exceed 4%. Improvement and
      satisfaction correlated significantly with bladder and bowel domain scores. Test
      retest reliability showed moderate to good agreement. The questionnaire was
      sensitive to change with a large effect size. The improvement of bladder symptoms
      in 91% of the women correlated with the domain score. CONCLUSION: The validated
      German pelvic floor questionnaire including a post-treatment module assesses
      symptoms, improvement and satisfaction in a reliable and reproducible fashion.

PMID- 21898281
TI  - [Reimplantation of the ureter in psoas hitch technique and Boari-plasty].

PMID- 21898309
TI  - [Geriatric psychiatry in the low countries, by young and old].

PMID- 21898310
TI  - [Prevention of depression and anxiety in older people].
AB  - BACKGROUND: In older people, sub-threshold symptom levels of depression or
      anxiety are characterised by a high prevalence and an unfavourable prognosis.
      They are the best predictors of the onset of full-blown disorders. There is an
      urgent need to develop effective preventative strategies. AIM: To determine the
      effectiveness and feasibility of an indicated depression- and anxiety- prevention
      programme for older people. METHODS: 170 individuals (75+) with sub-threshold
      symptom levels of depression or anxiety were randomized between a preventive
      intervention programme consisting of watchful waiting, bibliotherapy, problem
      solving treatment, and re-referral to primary care to discuss medication, or
      usual care. RESULTS: The intervention halved the incidence of (DSM-IV) depressive
      and anxiety disorders. CONCLUSION: A stepped-care approach to the prevention of
      depression and anxiety in later life was successful in halving the incidence of
      depressive and anxiety disorders after one year, were cost-effective, and the
      favourable effects were sustained for up to 24 months.

PMID- 21898311
TI  - [Prevention is coming of age].

PMID- 21898312
TI  - [Treatment of anxiety disorders in the elderly].
AB  - AIM: To collect empirical evidence concerning the effectiveness of the treatment
      of anxiety disorders in the elderly. METHOD: Meta-analysis and randomised
      controlled trials. RESULTS: Meta-analysis showed that cognitive behavioural
      therapy (CBT) was more successful than waiting-list control or active control as
      a treatment for older persons with anxiety disorders. In a direct comparison of
      the treatment of older persons with panic disorder (PD) both CBT an paroxetine
      were found to be more effective than waiting-list control. CBT was more
      successful in reducing avoidance behaviours in older persons with PD. Older
      persons with reported fewer and less severe agoraphobic cognitions than younger
      patients, but there was no difference between the severity of agoraphobic
      avoidance in older patients with PD and younger patients with PD. CONCLUSION:
      There is sufficient empirical evidence to support the effectiveness of CBT in the
      treatment of older persons with anxiety disorders. In assessing the severity of
      PD in the elderly, one should carefully consider the severity of avoidance
      behaviours. Because no difference was found between the effectiveness of CBT and
      paroxetine for the treatment of PD in the elderly and because was more effective
      in reducing avoidance behaviours in older patients with PD than in younger
      patients with pd, there seems to be a slight preference for CBT in the case of
      older patients with PD. Older age is not associated with a poorer outcome of
      treatment with CBT.

PMID- 21898313
TI  - [Anxiety in the elderly: from a lack of recognition to improved diagnosis and
      suitable treatment].

PMID- 21898314
TI  - [Cognitive deficits in late-life depression].
AB  - BACKGROUND: Depression in later life is often accompanied by cognitive deficits
      that can mimic those of (beginning) dementia. These deficits are expected to
      vanish when the depression lifts, but this does not always happen. AIM: To
      provide an overview of recent research into cognitive deficits in older patients
      with depression. METHOD: The recent literature was reviewed selectively. RESULTS:
      The cognitive deficits of older persons with depression often persist and are not
      related to the severity of the symptoms, remission status or the use of
      antidepressants. Imaging research in clinical and epidemiological populations
      strongly suggests that these cognitive deficits are due to neuropathological
      changes of microvascular origin. Some people with depression run an increased
      risk of developing dementia. CONCLUSION: The triad 'depression-cognitive
      impairment-vascular disease' may identify individuals at increased risk of
      dementia and is sometimes, accompanied by neurodegenerative and neuroinflammatory
      processes. The treatment of vascular disease in older adults with depression is
      therefore a promising starting-point for the selective prevention of dementia.

PMID- 21898315
TI  - [The link between vascular disease, depression and cognitive deterioration in the
      elderly. Has the vascular depression hypothesis proofed to be correct?].

PMID- 21898316
TI  - [Depressive symptoms, cortisol, visceral fat and metabolic syndrome].
AB  - BACKGROUND: Metabolic syndrome might explain the relationship between depression
      and cardiovascular disease. AIM: To examine the (longitudinal) relationship
      between depressive symptoms, cortisol and metabolic syndrome, especially visceral
      fat. METHODS: Our study derives data on depressive symptoms, cortisol, visceral
      fat and metabolic syndrome obtained from three different cohorts of older persons
      (Inchianti, lasa, Health abc). RESULTS: Metabolic dysregulation, especially in
      relation to fat occurs mainly in depressed persons with hypercortisolemia. There
      seems to be a vicious cycle between depressive symptoms and visceral fat.
      CONCLUSION: Early detection of metabolic disturbances in depressed patients might
      prevent cardiovascular outcomes. Future research should investigate whether the
      treatment of depression could positively influence metabolic syndrome, and
      whether, conversely, the treatment of metabolic syndrome could relieve
      depression.

PMID- 21898317
TI  - [Depression as a physical disorder].

PMID- 21898318
TI  - [Imaging of language and communication in dementia].
AB  - BACKGROUND: Social interaction in patients with dementia is compromised by
      language problems and impairment of other cognitive domains involved in
      communication. AIM: To describe language and communication problems in patients
      with dementia and to provide insight into the neurological basis of these
      problems. METHOD: Our study is based on some of our own research findings and on
      relevant literature concerning the imaging of language and communication in
      patients with Alzheimer's disease and frontotemporal degeneration. RESULTS:
      Imaging revealed that the clinical expression of communicative disorders in
      patients with cortical neurodegeneration depends on regional brain atrophy and a
      possible functional reorganisation triggered by neuropathological changes.
      CONCLUSION: Brain imaging increases our knowledge about the pathogenesis of
      communicative disorders in dementia.

PMID- 21898319
TI  - [The many faces of our language].

PMID- 21898320
TI  - [The immune system and Alzheimer's disease].
AB  - BACKGROUND: It has still not been established unequivocally whether vascular risk
      factors and inflammatory reactions, determined by heredity, are a cause or a
      result of Alzheimer's disease AIM: If the offspring of parents with AD have more
      risk factors and more frequent and severe inflammatory reactions than the
      offspring of parents without AD , this argues strongly in favor of a causal
      relationship between vascular risk factors, a pro-inflammatory cytokine response
      and AD. AIM: To determine whether the offspring of parents with ad have more risk
      factors and more frequent and severe inflammatory reactions than the offspring of
      parents without ad. method Vascular risk-factors, pro-inflammatory cytokines and
      the apoe genotype were determined in 206 offspring of parents with ad and in 200
      offspring of parents without AD. RESULTS: Offspring of parents with ad carried
      more apoe epsilon4 than offspring of parents without ad (47% vs 21%). Middle-aged
      offspring of parents with a history of ad also had higher blood pressure and a
      greater atherosclerotic burden than the offspring of parents without AD. Also
      their response to the pro-inflammatory cytokine was significantly higher.
      CONCLUSION: Hypertension and an inherited pro-inflammatory cytokine profile in
      middle age are early risk factors that contribute to the development of ad in old
      age. Offspring with a parental history of AD should therefore be offered
      screening and treatment for hypertension and have their blood pressure checked so
      that the development of AD in old age can be prevented.

PMID- 21898321
TI  - [What do we really mean by Alzheimer's?].

PMID- 21898322
TI  - [The role of CSF markers in the early diagnosis of Alzheimer's disease].
AB  - BACKGROUND: Biomarkers in cerebrospinal fluid (CSF) are being used increasingly
      to diagnose early Alzheimer's disease (AD). A CSF profile that is suggestive of
      ad is an abnormal ratio of the proteins Ab1-42 to total tau. AIM: To describe the
      prevalence and prognosis of a CSF profile in patients without dementia but with
      subjective memory problems and mild cognitive impairments (MCI) at a memory
      clinic. METHOD: A multi-centre study. RESULTS: A European multi-centre study
      showed that a CSF AD profile was often present in patients with subjective
      complaints and patients with MCI . The CSF AD profile predicted a decline in
      cognition and daily functioning over a period of 3 years in patients with MCI.
      Patients with amnestic MCI and a CSF AD profile developed AD more often within
      this period than patients without this profile. CONCLUSION: CSF markers
      suggestive of ad are common in persons without dementia. It may be possible to
      use these markers for the prognosis of patients who have MCI .

PMID- 21898323
TI  - [Searched for and found: non-demented patients with Alzheimer's disease].

PMID- 21898324
TI  - [The costs and benefits of an integrated approach to dementia].
AB  - BACKGROUND: An integrated approach to dementia is generally recommended because
      no one discipline is adequately equipped it deal with the complex psychic,
      physical and social problems that are inherent in dementia. A multidisciplinary
      approach, however, leads inevitably to higher costs. It is not known what the
      cost/benefit ratio will be. AIM: To describe our research into the costs and
      benefits of an integrated approach to dementia involving the use of a diagnostic
      research centre for psycho-geriatrics and thereafter to compare our findings with
      the results of other studies of the costs and benefits of an integrated approach.
      METHOD: We performed a prospective and randomised efficiency study and we
      compared our findings with the results of other studies of the costs and benefits
      of an integrated approach. We reviewed recent literature. RESULTS: The DRC-PG was
      more effective than normal care as far as the patients' quality of life was
      concerned, but was not more expensive. It can therefore be regarded as a cost
      effective facility for ambulatory patients with dementia. Three other studies
      provided additional empirical evidence of the success of a similar integrated
      approach in various sectors involved in the care of patients with dementia.
      CONCLUSION: An integrated approach with regard to the diagnosis, treatment and
      management of dementia produces favourable results. More research is needed into
      the efficacy and cost-effectiveness of integrated care programmes. This should
      result in improvements in the care and treatment of patients with dementia.

PMID- 21898325
TI  - [Collaborative care works].

PMID- 21898326
TI  - [Elderly patients with schizophrenia: prevalence and distribution of age at onset
      in a psychiatric catchment area in Amsterdam].
AB  - BACKGROUND: Elderly patients with schizophrenia are underrepresented in the
      literature on schizophrenia, although they constitute a rapidly growing group
      with specific characteristics. The Amsterdam-based study entitled 'Schizophrenia
      in Old Age' is currently examining the clinical and psychosocial functioning of a
      cohort of older patients with schizophrenia. AIM: To ascertain the one-year
      prevalence of schizophrenia and the distribution according to age at onset and
      gender in patients aged 60 years or over within a specific psychiatric catchment
      area. METHOD: The study is based on the case register of a Mental Health
      Organisation during 1-7-2007 to 30-6-2008. RESULTS: The one-year prevalence of
      schizophrenia was 0.55 % (95% ci: 0.46-0.64). In more than one in three patients
      the age of onset was 40 years or over. Women outnumbered men, even in the early
      onset schizophrenia subgroup. CONCLUSION: We found the prevalence of
      schizophrenia among older persons to be comparable to the prevalence among
      younger populations. The considerable number of patients who developed
      schizophrenia at an advanced age and the preponderance of women are
      distinguishing features of older persons with schizophrenia.

PMID- 21898327
TI  - [Elderly with late-onset schizophrenia].

PMID- 21898328
TI  - [Diagnosis and assessment of psychopathological symptoms in Parkinson's disease].
AB  - BACKGROUND: Parkinson's disease(PD) is a multidimensional disorder characterized
      primarily by motor symptoms, but often accompanied by non-motor symptoms,
      including psychopathological and autonomic symptoms. AIM: To provide an overview
      of current knowledge concerning the diagnosis, assessment and epidemiology of a
      number of psychopathological syndromes in PD. METHODS: Relevant literature is
      discussed. RESULTS: Depressive disorders, apathy, anxiety, cognitive impairment
      and hallucinations are all common in PD . For most of these syndromes, there is
      consensus regarding diagnostic criteria, and reliable rating scales are
      available. In general, an inclusive approach is recommended, which means that
      without interpretation or attribution, all symptoms present contribute to a
      psychopathological diagnosis. All psychopathological syndromes are more common in
      the hypokinetic rigid subtype of the disease. CONCLUSION: The recognition and
      treatment of psychopathological symptoms in PD require specific expertise. In the
      treatment of pd patients, therefore, it is essential that there should be
      multidisciplinary collaboration between the neurologist, the neuropsychologist
      and the psychiatrist.

PMID- 21898329
TI  - [Cooperation between neurologist and psychiatrist improves care].

PMID- 21898330
TI  - The fentanyl/etomidate-anesthetized beagle (FEAB) model in safety pharmacology
      assessment.
AB  - This unit describes a procedure for performing safety studies in the anesthetized
      beagle dog. Detailed are the anesthetic regime, the surgical procedure, and all
      materials needed to perform cardiovascular, central nervous system, and
      respiratory safety studies in these animals. An overview of all parameters that
      can be measured and calculated is provided, as are experimental protocols.
      Endpoints discussed include hemodynamic, electrocardiological, respiratory,
      arterial blood, and electroencephalogical parameters. Also presented are a
      formula to correct QT interval for changes in core body temperature and an
      overview of changes in ECG, MAP, and EEG traces that may occur during safety
      studies. The information provided yields a multiparametric model for performing
      reliable safety studies in anesthetized dogs.

PMID- 21898331
TI  - Preparation of HCV NS3 and NS5B proteins to support small-molecule drug
      discovery.
AB  - Production of high-quality, well-characterized recombinant proteins facilitates
      screening of compound libraries. The protocols detailed in this unit are used to
      purify three recombinant enzymes that are widely used in HCV research: the HCV
      NS3 protease domain, the helicase domain as an NS3+NS4A complex, and the NS5B RNA
      dependent RNA polymerase. The active enzymes are purified to homogeneity by two
      column chromatography to support a screening program for HCV inhibitors.

PMID- 21898332
TI  - Biochemical evaluation of HCV NS3 protease inhibitors.
AB  - This unit describes assays for characterizing the potency and mechanism of action
      of NS3 protease inhibitors. Determination of IC(50) values is described using in
      vitro expressed and purified NS3 protease. This assay can also be used for the
      rapid exploration of structure-activity relationships. Another protocol describes
      using the full-length NS3/4A complexes expressed in HCV replicon cell lines for a
      rapid alternative method for assessing protease activity without requiring
      conventional protein expression and purification. A method is then provided for
      determination of inhibitor K(i), which more accurately assesses the potency of
      inhibitors compared to the IC(50) assay, particularly for potent inhibitors that
      reach the sensitivity limit for the basic IC(50) assay. The final protocol
      describes how to determine the reversibility of inhibitor binding to the enzyme,
      an important parameter that can affect the pharmacodynamic properties of a
      compound.

PMID- 21898333
TI  - Orthotopic models of esophageal carcinoma and their use in drug discovery.
AB  - The protocol detailed in this unit is for the establishment of an orthotopic
      model of human esophageal adenocarcinoma in NMRI/nu mice. The resultant tumor has
      high metastatic potential, spreading readily to liver, lungs, and lymph nodes.
      This model is useful for studying primary esophageal carcinoma, tumor biology,
      pathogenesis, tumor progression, metastatic homing, and the efficacy of
      therapeutic approaches for treating this condition. The practical use of this
      preclinical model for drug discovery is illustrated with data from a study on the
      chemotherapeutic effects of HER2-targeted therapy.

PMID- 21898334
TI  - Pre-clinical mouse models of primary and metastatic pleural cancers of the lung
      and breast and the use of bioluminescent imaging to monitor pleural tumor burden.
AB  - Malignant pleural disease (MPD) results in an estimated 150,000 cases of
      malignant pleural effusions (MPE) annually. The most common malignancies
      associated with MPD are primary malignant pleural mesothelioma (MPM) and
      metastatic lung cancer, breast cancer, and lymphoma. MPM is a rare, regionally
      aggressive malignancy whose incidence is increasing secondarily to the latency of
      disease progression. MPD is characteristic of advanced-stage pleural disease and
      portends a grave clinical prognosis with a median survival between 3 and 12
      months. Preclinical investigations conducted in flank and intraperitoneal tumor
      models do not fully recapitulate the pleural tumor microenvironment, and the
      results are not directly translatable to the clinical setting. The protocol
      described herein provides a mouse model of MPM and MPD from nonhematogenous
      tumors, resulting in reproducible tumor location, tumor progression, animal
      survival, and histopathology. Pleural tumor growth in this model resembles the
      regionally aggressive clinical course and tumor microenvironment of human pleural
      cancers and provides an optimal animal model to investigate MPD biology and
      therapies.

PMID- 21898335
TI  - The colorimetric detection and quantitation of total protein.
AB  - Protein quantification is an important step for handling protein samples for
      isolation and characterization; it is a prerequisite step before submitting
      proteins for chromatographic, electrophoretic, or immunochemical analysis and
      separation. Colorimetric methods are fast, simple, and not laborious. This unit
      describes a number of assays able to detect protein concentrations in the low
      microgram to milligram per milliliter ranges in a variety of formats.

PMID- 21898336
TI  - Transfection by electroporation.
AB  - Electroporation--the use of high-voltage electric shocks to introduce DNA into
      cells--can be used with most cell types, yields a high frequency of both stable
      transformation and transient gene expression, and, because it requires fewer
      steps, can be easier than alternate techniques. This unit describes
      electroporation of mammalian cells, including ES cells for the preparation of
      knock-out, knock-in, and transgenic mice. Protocols are described for the use of
      electroporation in vivo to perform gene therapy for cancer therapy and DNA
      vaccination. Also described are modifications for preparation and transfection of
      plant protoplasts.

PMID- 21898337
TI  - A dual-chamber model of the female genital tract to evaluate epithelial toxicity
      of candidate anti-HIV microbicides.
AB  - Heterosexual transmission of human immunodeficiency virus (HIV) is the
      predominant mode of infection worldwide. The early steps of transepithelial
      infection are crucial, but how exactly infection is established in the female
      genital tract (FGT) is still under debate. Using epithelial cells originating
      from the FGT and primary cells as subepithelial HIV target cells, an in vitro
      dual-chamber model of the FGT was developed. Here we describe how this in vitro
      model can be used to assess the cellular toxicity and anti-HIV activity of
      antiretrovirals and formulations thereof that are intended to be used as
      microbicides.

PMID- 21898338
TI  - Quantitative colocalization analysis of confocal fluorescence microscopy images.
AB  - Colocalization is an important finding in many cell biological studies. This unit
      describes a protocol for quantitative evaluation of images with colocalization
      based on the calculation of a number of specialized coefficients. First, images
      of double-stained sections are subjected to background correction. Then, various
      coefficients are calculated. Meanings of the coefficients and a guide to
      interpretation of their results indicating either presence or absence of
      colocalization are given. Success in colocalization studies depends on the
      quality of analyzed images, proper preparation of the images for coefficients
      calculations, and correct interpretation of obtained results. This protocol helps
      to ensure reliability of colocalization coefficients calculations.

PMID- 21898339
TI  - Immunoblotting and immunodetection.
AB  - Immunoblotting (western blotting) is used to identify specific antigens
      recognized by polyclonal or monoclonal antibodies. This unit provides protocols
      for all steps, starting with solubilization of the protein samples, usually by
      means of SDS and reducing agents. Following solubilization, the material is
      separated by SDS-PAGE and the antigens are electrophoretically transferred to a
      membrane, a process that can be monitored by reversible staining with Ponceau S.
      The transferred proteins are bound to the surface of the membrane, providing
      access to immunodetection reagents. After nonspecific binding sites are blocked,
      the membrane is probed with the primary antibody and washed. The antibody-antigen
      complexes are tagged with horseradish peroxidase or alkaline phosphatase coupled
      to a secondary anti-IgG antibody, and detected using appropriate chromogenic or
      luminescent substrates. Finally, membranes may be stripped and reprobed.

PMID- 21898340
TI  - Symptomatic effects of chondroitin 4 and chondroitin 6 sulfate on hand
      osteoarthritis: a randomized, double-blind, placebo-controlled clinical trial at
      a single center.
AB  - OBJECTIVE: To evaluate the symptomatic effects of highly purified chondroitin 4
      and chondroitin 6 sulfate (CS) therapy in patients with osteoarthritis (OA) of
      the hand. METHODS: This investigator-initiated, single-center, randomized, double
      blind, placebo-controlled clinical trial included 162 symptomatic patients with
      radiographic evidence of hand OA (American College of Rheumatology criteria).
      Inclusion criteria included patient's assessment of global spontaneous hand pain
      of at least 40 mm on a 0-100-mm visual analog scale (VAS) and functional
      impairment of at least 6 (0-30 scale) on the Functional Index for Hand OA (FIHOA)
      in the most symptomatic hand. Patients received either 800 mg of CS (n = 80
      patients) or placebo (n = 82 patients) once daily for 6 months and were analyzed
      in an intent-to-treat approach. The two primary outcomes were the change in the
      patient's assessment of global spontaneous hand pain and in hand function (by
      FIHOA score) from baseline to month 6. Secondary outcomes were improvement in
      grip strength, duration of morning stiffness, acetaminophen consumption, and the
      investigator's global impression of treatment efficacy. RESULTS: There was a
      significantly more pronounced decrease in the patient's global assessment of hand
      pain in the CS group than in the placebo group (difference VAS scores -8.7 mm; P
      = 0.016). Hand function improved significantly more in the CS group than in the
      placebo group (difference in FIHOA scores -2.14; P = 0.008). There was a
      statistically significant between-group difference in favor of CS for the
      duration of morning stiffness and for the investigator's global impression of
      treatment efficacy. Changes in grip strength, acetaminophen consumption, and
      safety end points were not significantly different between the two groups.
      CONCLUSION: This study demonstrates that CS improves hand pain and function in
      patients with symptomatic OA of the hand and shows a good safety profile.

PMID- 21898341
TI  - Nongenomic glucocorticoid signaling: new targets for immunosuppressive therapy?

PMID- 21898342
TI  - Immune responses against domain I of beta(2)-glycoprotein I are driven by
      conformational changes: domain I of beta(2)-glycoprotein I harbors a cryptic
      immunogenic epitope.
AB  - OBJECTIVE: The presence of autoantibodies against a cryptic epitope in domain I
      of beta(2)-glycoprotein I (beta(2)GPI) is strongly associated with thrombotic
      events in patients with the antiphospholipid syndrome. We hypothesized that a
      conformational change could be a trigger for the formation of antibodies against
      domain I of beta(2)GPI. Therefore, we investigated whether immune responses
      against beta(2)GPI are related to its conformation. METHODS: Conformational
      changes in beta(2)GPI were studied using various techniques, either upon binding
      to cardiolipin or after disruption of the internal disulfide bonds. The
      immunogenicity of beta(2)GPI in different conformations as well as the individual
      domains of beta(2)GPI were studied in vivo by monitoring the generation of
      antibodies after intravenous administration of beta(2)GPI to mice. Furthermore,
      plasma samples from these mice were assessed for lupus anticoagulant activity and
      thrombin-antithrombin complex levels. RESULTS: We observed that the interaction
      of beta(2)GPI with cardiolipin induced a conformational change in beta(2)GPI:
      electron microscopy revealed that beta(2)GPI assembled into polymeric meshworks.
      We next investigated the immunogenicity of both human and murine beta(2)GPI in
      mice. Both human and murine beta(2)GPI combined with cardiolipin and misfolded
      beta(2)GPI triggered antibody formation against the native protein as well as
      against domain I of beta(2)GPI, while native beta(2)GPI was not immunogenic. In
      addition, we observed that anti-domain I antibodies developed in mice injected
      with domain I of beta(2)GPI, and that antibodies did not develop in mice injected
      with domains II-V. The induced anti-domain I antibodies prolonged the dilute
      Russell's viper venom plasma clotting time. The plasma of mice with anti-domain I
      antibodies had increased levels of circulating thrombin-antithrombin complexes.
      CONCLUSION: The results of our studies indicate that the exposure of cryptic
      epitopes due to conformational changes in beta(2)GPI can induce autoantibody
      formation.

PMID- 21898343
TI  - Origin and functional activity of the membrane-bound glucocorticoid receptor.
AB  - OBJECTIVE: Glucocorticoids (GCs) exert their antiinflammatory and
      immunosuppressive effects in humans primarily via the cytosolic GC receptor (cGR)
      but also via rapid, nongenomic mechanisms. Most likely, membrane-bound GRs (mGR)
      are involved in nongenomic GC signaling. The aim of this study was to investigate
      the origin and functional activity of mGR. METHODS: We analyzed the origin of mGR
      using mGR-expressing HEK 293T cells, by transient and stable RNA interference
      mediated GR reduction. GR messenger RNA (mRNA) and cGR and mGR protein levels
      were analyzed by real-time quantitative polymerase chain reaction,
      immunoblotting, and high-sensitivity immunofluorescence staining. Furthermore, we
      analyzed the functional activity of mGR, using membrane-impermeable bovine serum
      albumin (BSA)-bound dexamethasone (DEX-BSA) in human monocytes. Membrane-bound GR
      expressing monocytes were treated with DEX, DEX-BSA, or BSA. Cell lysates were
      analyzed using PepChip arrays in order to identify kinases triggered by DEX-BSA,
      with validation using Bio-Plex assays and immunoblotting. RESULTS: Our data
      showed that transient reduction of GR mRNA in HEK 293T cells decreased cGR
      protein levels but not mGR protein levels. However, stably transfected cells
      showed reduced cGR protein expression and significantly reduced mGR protein
      expression. Furthermore, 51 kinase substrates were identified for which
      phosphorylation was either reduced or increased. We observed p38 MAP kinase
      (MAPK) as one possible upstream kinase. Validation of these data by Bio-Plex
      phosphoprotein assay and immunoblotting showed increased phosphorylation of p38
      MAPK after treatment with DEX-BSA. CONCLUSION: Our data demonstrate that the
      human GR gene encodes for both cGR and mGR. Membrane-bound GR retains functional
      activity, as indicated by induced phosphorylation of p38 MAPK due to DEX-BSA
      treatment. Membrane-bound GR-mediated cellular signaling needs to be investigated
      further in order to clarify its therapeutic potential.

PMID- 21898344
TI  - Treatment of pediatric Erdheim-Chester disease with interleukin-1-targeting
      drugs.

PMID- 21898345
TI  - Evidence of the contribution of the X chromosome to systemic sclerosis
      susceptibility: association with the functional IRAK1 196Phe/532Ser haplotype.
AB  - OBJECTIVE: Several autoimmune disorders, including systemic sclerosis (SSc), are
      characterized by a strong sex bias. To date, it is not known whether genes on the
      sex chromosomes influence SSc susceptibility. Recently, an IRAK1 haplotype that
      contains the 196Phe functional variant (rs1059702), located on Xq28, was found to
      confer susceptibility to systemic lupus erythematosus (SLE). This study was
      undertaken to test for an association between SSc and the IRAK1 SLE risk
      haplotype. METHODS: We tested for an association with the IRAK1 SLE risk
      haplotype in a discovery set of 849 SSc patients and 625 controls. IRAK1
      rs1059702 was further genotyped in a replication set, which included Caucasian
      women from Italy (493 SSc patients and 509 controls) and Germany (466 SSc
      patients and 1,083 controls). RESULTS: An association between the IRAK1 haplotype
      and SSc was detected in the discovery set. In both the discovery and replication
      sets, the rs1059702 TT genotype was found to be associated with specific SSc
      subsets, highlighting a potential contribution to disease severity. A meta
      analysis provided evidence of an association of both the T allele and TT genotype
      with the overall disease, with an odds ratio (OR) of 1.20 and 95% confidence
      interval (95% CI) of 1.06-1.35 for the T allele (P = 0.003) and an OR of 1.49 and
      95% CI of 1.06-2.10 for the TT genotype (P = 0.023). However, the most notable
      associations were observed with the diffuse cutaneous, anti-topoisomerase I
      antibody positive, and SSc-related fibrosing alveolitis subsets (OR 2.35 [95% CI
      1.51-3.66], P = 1.56 * 10(-4), OR 2.84 [95% CI 1.87-4.32], P = 1.07 * 10(-6), and
      OR 2.09 [95% CI 1.35-3.24], P = 9.05 * 10(-4), respectively). CONCLUSION: Our
      study provides the first evidence of an association between IRAK1 and SSc,
      demonstrating that a sex chromosome gene directly influences SSc susceptibility
      and its phenotypic heterogeneity.

PMID- 21898346
TI  - Independent association of joint space narrowing and osteophyte formation at the
      knee with health-related quality of life in Japan: a cross-sectional study.
AB  - OBJECTIVE: To clarify the individual associations of joint space narrowing (JSN)
      and osteophytosis at the knee with quality of life (QOL) in Japanese men and
      women using a large-scale population-based cohort from the Research on
      Osteoarthritis Against Disability (ROAD) study. METHODS: The associations of
      minimum joint space width (JSW) and osteophyte area in the medial compartment of
      the knee with QOL parameters, such as the Western Ontario and McMaster
      Universities Osteoarthritis Index (WOMAC), were examined. Minimum JSW and
      osteophyte area in the medial compartment of the knee were measured using a
      computer-aided system for the diagnosis of knee osteoarthritis. RESULTS: Of the
      3,040 participants in the ROAD study, the present study included 2,039
      participants age 40 years or older who completed the questionnaires (741 men and
      1,298 women with a mean +/- SD age of 68.6 +/- 10.9 years). Multiple regression
      analysis after adjustment for age and body mass index showed that minimum JSW was
      significantly associated with scores on the pain domains of the WOMAC in men and
      women, while osteophyte area was significantly associated with scores on the
      physical function domains of the WOMAC in men and women. CONCLUSION: The findings
      of this cross-sectional study using a large-scale population from the ROAD study
      indicate that JSN and osteophytosis are independently associated with QOL.

PMID- 21898347
TI  - Clinical images: epidural hematoma in ankylosing spondylitis.

PMID- 21898348
TI  - Distinguishing the proapoptotic and antiresorptive functions of risedronate in
      murine osteoclasts: role of the Akt pathway and the ERK/Bim axis.
AB  - OBJECTIVE: Nitrogen-containing bisphosphonates are one of the most successful
      therapeutics for osteoporosis. The aim of this study was to elucidate the
      functional mechanism of one of the typical nitrogen-containing bisphosphonates,
      risedronate. METHODS: Osteoclasts generated from murine bone marrow macrophages
      were treated with risedronate in vitro, and its effects on apoptosis and bone
      resorbing activity were examined. The mechanism of action of risedronate was
      examined by gene induction of constitutively active Akt-1 and constitutively
      active MEK-1, and by gene deletion of Bim. Bim(-/-)  mice, in which osteoclasts
      were resistant to apoptosis, were treated with risedronate and analyzed
      radiographically, biochemically, and histologically. RESULTS: Risedronate induced
      osteoclast apoptosis through the mitochondria-dependent pathway with an increased
      expression of Bim, and the proapoptotic effect of risedronate was suppressed by
      Bim deletion and constitutively active MEK-1 introduction. In contrast, the
      risedronate-induced suppression of bone resorption was completely reversed by
      inducing constitutively active Akt-1, but not by Bim deletion or constitutively
      active MEK-1 introduction. These results suggested that apoptosis and bone
      resorbing activity of osteoclasts were regulated through the ERK/Bim axis and the
      Akt pathway, respectively, both of which were suppressed by risedronate. Although
      osteoclast apoptosis in response to risedronate administration was suppressed in
      the Bim(-/-)  mice, risedronate treatment increased bone mineral density in Bim(
      /-)  mice at a level equivalent to that in wild-type mice. CONCLUSION: Our
      findings indicate that the antiresorptive effect of risedronate in vivo is mainly
      mediated by the suppression of the bone-resorbing activity of osteoclasts and not
      by the induction of osteoclast apoptosis.

PMID- 21898350
TI  - Rheumatoid factor: the end of the term as we know it? Comment on the editorial by
      Liao et al.

PMID- 21898349
TI  - Localized expression of tenascin in systemic sclerosis-associated pulmonary
      fibrosis and its regulation by insulin-like growth factor binding protein 3.
AB  - OBJECTIVE: To determine the role of insulin-like growth factor binding protein 3
      (IGFBP-3) in mediating the effects of transforming growth factor beta (TGFbeta)
      on tenascin-C (TN-C) production and to assess the levels of TN-C in vivo in
      patients with systemic sclerosis (SSc)-associated pulmonary fibrosis. METHODS:
      Human primary lung fibroblasts were stimulated with TGFbeta or IGFBP-3 in the
      presence or absence of specific small interfering RNAs and chemical inhibitors of
      the signaling cascade. TN-C levels in lung tissue specimens obtained from
      patients with SSc-associated pulmonary fibrosis were assessed using
      immunohistochemical analysis and were compared with the levels in specimens
      obtained from normal donors. TN-C levels were quantified in sera from normal
      donors and patients with SSc with or without pulmonary fibrosis, using an enzyme
      linked immunosorbent assay. RESULTS: IGFBP-3 mediated the induction of TN-C by
      TGFbeta. Direct induction of TN-C by IGFBP-3 occurred in a p38 MAP kinase
      dependent manner. TN-C levels were abundant in lung tissues from patients with
      SSc and were localized to subepithelial layers of the distal airways. No TN-C was
      detectable around the proximal airways. Patients with SSc-associated pulmonary
      fibrosis had significantly higher levels of circulating TN-C compared with SSc
      patients without pulmonary fibrosis. Longitudinal samples obtained from patients
      with SSc before and after the onset of pulmonary fibrosis showed increased levels
      of TN-C after the onset of pulmonary fibrosis. CONCLUSION: IGFBP-3, which is
      overexpressed in fibrotic lungs, induces production of TN-C by subepithelial
      fibroblasts. The increased lung tissue levels of TN-C parallel the levels
      detected in the sera of SSc patients with pulmonary fibrosis, suggesting that TN
      C may be a useful biomarker for SSc-related pulmonary fibrosis.

PMID- 21898351
TI  - A two-stage approach to the treatment of hyperuricemia in gout: the "dirty dish"
      hypothesis.
AB  - OBJECTIVE: It is commonly accepted that the target serum urate level in patients
      receiving urate-lowering therapy for dissolution of urate crystals in
      hyperuricemia of gout is <6 mg/dl, and that patients with gout should continue
      urate-lowering therapy for the rest of their lives. This study was undertaken to
      reevaluate whether this stringent therapeutic target to dissolve crystals must be
      maintained lifelong to prevent new crystal formation. METHODS: In a prospective
      cohort of 211 patients with gout, urate-lowering therapy was withdrawn after 5
      years if no tophus was present at baseline, or 5 years after resolution of the
      last tophus. Data on recurrence of gout and on serum urate levels and other
      potentially associated variables were analyzed. RESULTS: Multivariate regression
      analysis of time to crystal-proven recurrence of gout showed that serum urate
      levels during urate-lowering treatment and after its withdrawal were
      independently related to gout recurrence. None of the patients who had average
      serum urate levels of <7 mg/dl after urate-lowering therapy withdrawal developed
      a crystal-proven recurrence of gout. Post hoc analysis showed that weight loss
      and use of drugs that lower serum urate, such as losartan or fenofibrate, were
      associated with serum urate levels of <7 mg/dl during followup after urate
      lowering therapy withdrawal; use of diuretics was associated with failure to
      achieve serum urate levels of <7 mg/dl during followup. CONCLUSION: Our data
      support the hypothesis that after appropriate long-term treatment of
      hyperuricemia in gout with urate crystal dissolution being the therapeutic
      target, lifelong treatment can be targeted to achieve serum urate levels just
      below the threshold for saturation to avoid new crystal formation, similar to
      cleaning a dirty dish: more is required to get it clean than to keep it clean.

PMID- 21898352
TI  - What do microRNAs mean for rheumatoid arthritis?

PMID- 21898353
TI  - Dimethylarginine dimethylaminohydrolase 2, a newly identified mitochondrial
      protein modulating nitric oxide synthesis in normal human chondrocytes.
AB  - OBJECTIVE: The mitochondrion is known to be important to chondrocyte survival.
      This study was undertaken to analyze protein expression profiles in chondrocyte
      mitochondria that are affected by interleukin-1beta (IL-1beta). METHODS: Normal
      human chondrocytes were isolated from knee cartilage obtained at autopsy from
      subjects with no history of joint disease. Cells were incubated for 48 hours with
      or without IL-1beta (5 ng/ml). Proteins were separated by 2-dimensional
      electrophoresis and stained with Sypro Ruby, Coomassie brilliant blue, or silver.
      Qualitative and quantitative analyses were carried out using PDQuest software.
      Proteins were identified by mass spectrometry using matrix-assisted laser
      desorption ionization-time-of-flight/time-of-flight technology. The proteomic
      results were validated by real-time polymerase chain reaction, Western blotting,
      and microscopy. Nitric oxide (NO) was quantified using Griess reagent. RESULTS:
      Comparative analysis revealed differential expression of signal transduction
      proteins that regulate cytoskeleton, transcription, metabolic, and stress-related
      pathways. In total extracts, dimethylarginine dimethylaminohydrolase 2 (DDAH-2)
      did not show any change in expression after stimulation with IL-1beta. However,
      in mitochondrial extracts, DDAH-2 expression was significantly increased after
      exposure to IL-1beta. Conventional immunofluorescence and confocal microscopy
      revealed the presence of DDAH-2 in the mitochondria of IL-1beta-stimulated
      chondrocytes. These results were reproducible in cartilage explants treated with
      IL-1beta. In addition, we demonstrated that inhibition of the expression of DDAH
      2, as well as interruption of its translocation to the mitochondria, reduced the
      NO production induced by IL-1beta. DDAH-2 protein expression was higher in
      osteoarthritic (OA) cartilage than in normal cartilage. CONCLUSION: In the
      present study, the presence of DDAH-2 in normal human chondrocytes and cartilage
      was identified for the first time. DDAH-2 could play an important role in IL
      1beta-induced NO production and in OA pathogenesis.

PMID- 21898354
TI  - Observational studies on the risk of cancer associated with tumor necrosis factor
      inhibitors in rheumatoid arthritis: a review of their methodologies and results.

PMID- 21898355
TI  - Treatment with tumor necrosis factor inhibitors and the risk of acute coronary
      syndromes in early rheumatoid arthritis.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is associated with an increased risk of
      ischemic heart disease, in both early and established RA. Data on the risk of
      ischemic heart disease in relation to therapy with tumor necrosis factor (TNF)
      antagonists (anti-TNF) are conflicting in patients with established RA and
      essentially lacking in those with early RA. In established RA, the risk of
      myocardial infarction has been linked to the response to anti-TNF therapies. The
      aim of this study was to determine the risk of acute coronary syndromes (ACS) in
      patients with early RA in relation to treatment with, and response to, anti-TNF.
      METHODS: A cohort consisting of patients in whom RA was diagnosed between 1999
      and 2007 was identified from the Swedish Rheumatology Register (n=6,000), from
      which information on disease activity and pharmacologic treatments was extracted.
      In a cohort study, the risk of first occurrence of an ACS was compared between
      patients treated with anti-TNF and those without exposure to anti-TNF, using
      hazard ratios (HRs). In a nested case-control study, the relationship between
      response to anti-TNF according to the European League Against Rheumatism (EULAR)
      response criteria and the risk of ACS was investigated. RESULTS: In the cohort
      study, treatment with anti-TNF was not related to any statistically significant
      alteration in the risk of ACS (HR 0.80, 95% confidence interval [95% CI] 0.52
      1.24). In the nested case-control study, a good or moderate EULAR treatment
      response at 3 months and at 6 months was not associated with a risk of ACS (odds
      ratio [OR] 1.7, 95% CI 0.5-5.1 and OR 1.5, 95% CI 0.3-6.9, respectively), when
      adjusted for disease activity before treatment start. CONCLUSION: In this study
      of patients treated with anti-TNF within the first years of RA, neither treatment
      with, nor response to, anti-TNF therapy could be linked to any statistically
      significant decrease in the risk of ACS.

PMID- 21898356
TI  - Macrophage positron emission tomography imaging as a biomarker for preclinical
      rheumatoid arthritis: findings of a prospective pilot study.
AB  - OBJECTIVE: To conduct a prospective pilot study to determine whether macrophage
      targeting by 11C-(R)-PK11195 positron emission tomography (PET) can visualize
      subclinical synovitis in arthralgia patients who have anti-citrullinated protein
      antibodies (ACPAs). METHODS: Twenty-nine arthralgia patients who were positive
      for ACPAs but did not have clinical arthritis were studied. High (spatial)
      resolution 11C-(R)-PK11195 PET scans of the hands and wrists were performed. For
      all metacarpophalangeal, proximal interphalangeal, and wrist joints (i.e., 22
      joints per patient), tracer uptake was scored semiquantitatively (0-3 scale) by 2
      observers who were blinded with regard to the clinical data. Patients were
      followed up prospectively for 24 months to investigate the development of
      clinical arthritis. RESULTS: Overall agreement and kappa values for the readings
      of the 2 observers were, respectively, 97% and 0.91 (95% confidence interval [95%
      CI] 0.74-1) at the patient level and 99% and 0.81 (95% CI 0.65-0.96) at the joint
      level. In 4 patients, at least 1 and as many as 5 PET-positive joints (score>=1)
      were found at baseline. Within 2 years of followup, 9 patients had developed
      clinical arthritis. This included all 4 patients with positive findings on the
      11C-(R)-PK11195 scan, who developed clinical arthritis in the hand/wrist region,
      as identified on PET scans. Of the 5 remaining arthritis patients with negative
      findings on PET scans, 2 developed arthritis in the hand joints and 3 developed
      arthritis at locations outside the field of view of the PET scanner. CONCLUSION:
      Subclinical arthritis in ACPA-positive arthralgia patients could be visualized by
      11C-(R)-PK11195 PET scanning and was associated with development of arthritis
      within 2 years of followup. This indicates that 11C-(R)-PK11195 PET may be useful
      in determining arthritis activity in the preclinical phase of RA.

PMID- 21898357
TI  - Prostaglandin D2 regulates joint inflammation and destruction in murine collagen
      induced arthritis.
AB  - OBJECTIVE: Prostaglandin D2 (PGD2) may exert proinflammatory or antiinflammatory
      effects in different biologic systems. Although this prostanoid and the enzymes
      responsible for its synthesis are up-regulated by interleukin-1beta (IL-1beta) in
      human chondrocytes in vitro, the role of PGD2 in arthritis remains unclear. This
      study was undertaken to investigate the role of PGD2 in the inflammatory response
      and in joint destruction during the development of collagen-induced arthritis
      (CIA) in mice. METHODS: PGD2 and cytokine levels in mice with CIA were determined
      by enzyme-linked immunosorbent assay. Expression of hematopoietic PGD synthase (h
      PGDS), lipocalin-type PGD synthase (l-PGDS), and DP1 and DP2 receptors was
      analyzed by immunohistochemical methods. PGE2 levels were determined by
      radioimmunoassay. RESULTS: The arthritic process up-regulated the expression of h
      PGDS, l-PGDS, DP1, and DP2 in articular tissue. PGD2 was produced in the joint
      during the early phase of arthritis, and serum PGD2 levels increased
      progressively throughout the arthritic process, reaching a maximum during the
      late stages of CIA. Treatment of arthritic mice with the DP1 antagonist MK0524
      soon after the onset of disease increased the incidence and severity of CIA as
      well as the local levels of IL-1beta, CXCL-1, and PGE2, whereas IL-10 levels were
      reduced. The administration of the DP2 antagonist CAY10595 did not modify the
      severity of arthritis. The injection of PGD2 into the paw, as well as the
      administration of the DP1 agonist BW245C, significantly lowered the incidence of
      CIA, the inflammatory response, and joint damage. CONCLUSION: Our findings
      indicate that PGD2 is produced in articular tissue during the development of CIA
      and plays an antiinflammatory role, acting through the DP1 receptor.

PMID- 21898358
TI  - The relationship of vibratory perception to dynamic joint loading, radiographic
      severity, and pain in knee osteoarthritis.
AB  - OBJECTIVE: Patients with knee osteoarthritis (OA) have been shown to have
      somatosensory deficits of the lower extremity. This study was designed to assess
      the association of these deficits with dynamic joint loading and their
      relationship to the structural and symptomatic severity of knee OA. METHODS:
      Subjects with symptomatic knee OA underwent evaluation of the vibratory
      perception threshold (VPT) using a biothesiometer at 5 sites at the lower
      extremity. Dynamic joint loading was assessed through gait analyses. Knee pain
      was evaluated using a visual analog scale score for pain based on the Western
      Ontario and McMaster Universities OA Index. Radiographic severity of knee OA was
      assessed using the Kellgren/Lawrence (K/L) grading scale on radiographs obtained
      with the knee in a standing position. RESULTS: Dynamic knee joint loading was
      directly associated with the VPT at the metatarsophalangeal (MTP) joint
      (Spearman's rho=0.384, P=0.033), indicating that the worse the vibratory sense,
      the higher the knee load during gait. The K/L severity grade was directly
      associated with the VPT at the MTP joint and lateral femoral condyle, after
      adjustment for age, sex, body mass index, and knee pain. After adjustment for
      confounders, there were no significant associations observed between the VPT and
      pain at any of the sites tested. CONCLUSION: These findings demonstrate an
      association between greater somatosensory deficits and higher dynamic loads in
      OA. They also demonstrate structural consequences associated with somatosensory
      deficits in OA, since the extent of sensory loss directly correlated with the
      radiographic severity of knee OA. However, there was no relationship observed
      between vibratory sense and symptomatic knee OA pain.

PMID- 21898360
TI  - Th2 and regulatory immune reactions contribute to IgG4 production and the
      initiation of Mikulicz disease.
AB  - OBJECTIVE: Mikulicz disease has been considered to be a subtype of Sjogren's
      syndrome (SS). However, recent studies have suggested that Mikulicz disease is an
      IgG4-related disease and is distinguishable from SS. In addition, it has been
      reported that both interleukin-4 (IL-4) and IL-10 induce IgG4 production and
      inhibit IgE. This study was undertaken to examine the expression of these
      cytokines in patients with Mikulicz disease and patients with SS. METHODS: Labial
      salivary gland (LSG) sections from 15 patients with Mikulicz disease and 18
      patients with SS were examined for subsets of the infiltrating lymphocytes,
      expression patterns of messenger RNA (mRNA) for cytokines/chemokines, and
      relationships between the IgG4:IgG ratio and the expression of mRNA for IL-4 or
      IL-10. RESULTS: Immunohistochemical analysis showed lymphocyte infiltration of
      various subsets in the LSGs of SS patients, and the selective infiltration of
      IgG4-positive plasma cells and Treg cells in the LSGs of Mikulicz disease
      patients. The levels of mRNA for both Th1 and Th2 cytokines and chemokines in
      LSGs from patients with SS were significantly higher than in controls, while the
      expression of both Th2 and Treg cells was significantly higher in the patients
      with Mikulicz disease than in controls. Furthermore, the expression of IL-4 or IL
      10 in the LSGs was correlated with the IgG4:IgG ratio. CONCLUSION: These results
      suggest that the pathogenesis of Mikulicz disease is different from that of SS.
      Mikulicz disease is a unique inflammatory disorder characterized by Th2 and
      regulatory immune reactions that might play key roles in IgG4 production.

PMID- 21898361
TI  - Investigating diproline segments in proteins: occurrences, conformation and
      classification.
AB  - The covalent linkage between the side-chain and the backbone nitrogen atom of
      proline leads to the formation of the five-membered pyrrolidine ring and hence
      restriction of the backbone torsional angle phi to values of -60  degrees +/- 30
      degrees  for the L-proline. Diproline segments constitute a chain fragment with
      considerably reduced conformational choices. In the current study, the
      conformational states for the diproline segment (( L) Pro-( L) Pro) found in
      proteins has been investigated with an emphasis on the cis and trans states for
      the Pro-Pro peptide bond. The occurrence of diproline segments in turns and other
      secondary structures has been studied and compared to that of Xaa-Pro-Yaa
      segments in proteins which gives us a better understanding on the restriction
      imposed on other residues by the diproline segment and the single proline
      residue. The study indicates that P(II) -P(II) and P(II) -alpha are the most
      favorable conformational states for the diproline segment. The analysis on Xaa
      Pro-Yaa sequences reveals that the Xaa-Pro peptide bond exists preferably as the
      trans conformer rather than the cis conformer. The present study may lead to a
      better understanding of the behavior of proline occurring in diproline segments
      which can facilitate various designed diproline-based synthetic templates for
      biological and structural studies.

PMID- 21898359
TI  - Cyclin-dependent kinase inhibitor p21, via its C-terminal domain, is essential
      for resolution of murine inflammatory arthritis.
AB  - OBJECTIVE: The mechanism responsible for persistent synovial inflammation in
      rheumatoid arthritis (RA) is unknown. Previously, we demonstrated that expression
      of the cyclin-dependent kinase inhibitor p21 is reduced in synovial tissue from
      RA patients compared to osteoarthritis patients and that p21 is a novel
      suppressor of the inflammatory response in macrophages. The present study was
      undertaken to investigate the role and mechanism of p21-mediated suppression of
      experimental inflammatory arthritis. METHODS: Experimental arthritis was induced
      in wild-type or p21-/- (C57BL/6) mice, using the K/BxN serum-transfer model. Mice
      were administered p21 peptide mimetics as a prophylactic for arthritis
      development. Lipopolysaccharide-induced cytokine and signal transduction pathways
      in macrophages that were treated with p21 peptide mimetics were examined by
      Luminex-based assay, flow cytometry, or enzyme-linked immunosorbent assay.
      RESULTS: Enhanced and sustained development of experimental inflammatory
      arthritis, associated with markedly increased numbers of macrophages and severe
      articular destruction, was observed in p21-/- mice. Administration of a p21
      peptide mimetic suppressed activation of macrophages and reduced the severity of
      experimental arthritis in p21-intact mice only. Mechanistically, treatment with
      the p21 peptide mimetic led to activation of the serine/threonine kinase Akt and
      subsequent reduction of the activated isoform of p38 MAPK in macrophages.
      CONCLUSION: These are the first reported data to reveal that p21 has a key role
      in limiting the activation response of macrophages in an inflammatory disease
      such as RA. Thus, targeting p21 in macrophages may be crucial for suppressing the
      development and persistence of RA.

PMID- 21898362
TI  - Structure and properties of camptothecin derivatives, their protonated forms, and
      model interaction with the topoisomerase I-DNA complex.
AB  - The structure and properties of the 11 Camptothecin derivatives (CPTs) and their
      different mono-, di-, and triprotonated forms, depending on the number of proton
      accepting centers in the molecules are studied both theoretically and
      experimentally by quantum chemical approaches, electronic absorption, and CD
      spectroscopy. The study of the protonated forms of the CPTs and search of the
      electron-withdrawing groups is crucial of the water-solubility of the novel
      medications. Thus, the model interaction of the different protonated molecular
      species with the Topoisomerase I-DNA complex are elucidated and discussed with a
      view to understand the mode of binding of the CPTs depending on the type of the
      substituents and pH of the medium.

PMID- 21898363
TI  - Invited review current progress and limitations of spider silk for biomedical
      applications.
AB  - Spider silk is a fascinating material combining remarkable mechanical properties
      with low density and biodegradability. Because of these properties and historical
      descriptions of medical applications, spider silk has been proposed to be the
      ideal biomaterial. However, overcoming the obstacles to produce spider silk in
      sufficient quantities and in a manner that meets regulatory demands has proven to
      be a difficult task. Also, there are relatively few studies of spider silk in
      biomedical applications available, and the methods and materials used vary a lot.
      Herein we summarize cell culture- and in vivo implantation studies of natural and
      synthetic spider silk, and also review the current status and future challenges
      in the quest for a large scale production of spider silk for medical
      applications.

PMID- 21898364
TI  - Effects of ring contraction on the conformational preferences of alpha
      substituted proline analogs.
AB  - The structural consequences derived from the incorporation of either a methyl or
      a phenyl group at the alpha carbon of proline were recently investigated by
      quantum mechanical calculations (J Org Chem 2008, 73, 3418). In this work, the
      effect produced by contraction of the pyrrolidine ring on such alpha-substituted
      proline analogs has been explored using the same computational methods.
      Specifically, the intrinsic conformational preferences of the N-acetyl-N'
      methylamide derivatives of the lower proline homolog L-azetidine-2-carboxylic
      acid (Aze), characterized by a four- instead of a five-membered ring, and its
      alpha-methyl (alphaMeAze) and alpha-phenyl (alphaPhAze) derivatives have been
      determined using quantum mechanical calculations and compared to those observed
      before for the proline counterparts. Replacement of the pyrrolidine ring by an
      azetidine cycle leads to a reduction of the conformational flexibility,
      especially for the Aze and alphaMeAze derivatives, which should be attributed to
      the quasi-planar geometry of the four-membered ring. Furthermore, the azetidine
      nitrogen shows pyramidalization, which depending on the peptide backbone
      conformation favors the formation of an attractive N-H...N interaction or
      alleviates a severe steric hindrance. Calculations on different environments
      predict that the tendency of alphaMeAze to adopt gamma-turns is higher than that
      of unsubstituted Aze and alpha-methylproline, this feature being in full
      agreement with the experimental observations available.

PMID- 21898365
TI  - Structure and pH-induced alterations of recombinant and natural spider silk
      proteins in solution.
AB  - The spinning process of spiders can modulate the mechanical properties of their
      silk fibers. It is therefore of primary importance to understand what are the key
      elements of the spider spinning process to develop efficient industrial spinning
      processes. We have exhaustively investigated the native conformation of major
      ampullate silk (MaS) proteins by comparing the content of the major ampullate
      gland of Nephila clavipes, solubilized MaS (SolMaS) fibers and the recombinant
      proteins rMaSpI and rMaSpII using (1) H solution NMR spectroscopy. The results
      indicate that the protein secondary structure is basically identical for the
      recombinant protein rMaSpI, SolMaS proteins, and the proteins in the dope, and
      corresponds to a disordered protein rich in 3(1) -helices. The data also show
      that glycine proton chemical shifts of rMaSpI and SolMaS are affected by pH, but
      that this change is not due to a modification of the secondary structure. Using a
      combination of NMR and dynamic light scattering, we have found that the spectral
      alteration of glycine is concomitant to a modification of the hydrodynamical
      diameter of recombinant and solubilized MaS. This led us to suggest new potential
      roles for the pH acidification in the spinning process of MaS proteins.

PMID- 21898366
TI  - Using FTIR to predict saccharification from enzymatic hydrolysis of alkali
      pretreated biomasses.
AB  - Fourier transform infrared, attenuated total reflectance (FTIR-ATR) spectroscopy
      combined with partial least squares (PLS) regression accurately predicted 72-h
      glucose and xylose conversions (g sugars/100 g potential sugars) and yields (g
      sugars/100 g dry solids) from cellulase-mediated hydrolysis of alkali-pretreated
      lignocellulose. Six plant biomasses that represent a variety of potential biofuel
      feedstocks--two switchgrass cultivars, big bluestem grass, a low-impact, high
      diversity mixture of 32 species of prairie biomasses, mixed hardwood, and corn
      stover--were subjected to four levels of low-temperature NaOH pretreatment to
      produce 24 samples with a wide range of potential digestibility. PLS models were
      constructed by correlating FTIR spectra of pretreated samples to measured values
      of gluose and xylose conversions and yields. Variable selection, based on 90%
      confidence intervals of regression-coefficient matrices, improved the predictive
      ability of the models, while simplifying them considerably. Final models
      predicted sugar conversions with coefficient of determination for cross
      validation (Q(2)) values of 0.90 for glucose and 0.89 for xylose, and sugar
      yields with Q(2) values of 0.92 for glucose and 0.91 for xylose. The sugar-yield
      models are noteworthy for their ability to predict enzymatic saccharification per
      mass dry solids without a priori knowledge of the composition of the solids. All
      peaks retained in the final regression coefficient matrices were previously
      assigned to chemical bonds and functional groups in lignocellulose, demonstrating
      that the models were based on real chemical information. This study demonstrates
      that FTIR spectroscopy combined with PLS regression can be used to rapidly
      estimate sugar conversions and yields from enzymatic hydrolysis of pretreated
      plant biomass.

PMID- 21898367
TI  - Kinetic and growth parameters of Arthrospira (Spirulina) platensis cultivated in
      tubular photobioreactor under different cell circulation systems.
AB  - Arthrospira platensis was cultivated in tubular photobioreactor in order to
      evaluate growth and biomass production at variable photosynthetic photon flux
      density (PPFD = 60, 120, and 240 umol photons m(-2)s(-1)) and employing three
      different systems for cell circulation, specifically an airlift, a motor-driven
      pumping and a pressurized system. The influence of these two independents
      variables on the maximum cell concentration (X(m)), cell productivity (P(x)),
      nitrogen-to-cell conversion factor (Y(X/N) ), photosynthetic efficiency (PE), and
      biomass composition (total lipids and proteins), taken as responses, was
      evaluated by analysis of variance. The statistical analysis revealed that the
      best combination of responses' mean values (X(m) = 4,055 mg L(-1), P(x) = 406 mg
      L(-1)day(-1), Y(X/N) = 5.07 mg mg(-1), total lipids = 8.94%, total proteins =
      30.3%, PE = 2.04%) was obtained at PPFD = 120 umol photons m(-2)s(-1); therefore,
      this light intensity should be considered as the most well-suited for A.
      platensis cultivation in this photobioreactor configuration. The airlift system
      did not exert any significant positive statistical influence on the responses,
      which suggests that this traditional cell circulation system could successfully
      be substituted by the others tested in this work.

PMID- 21898368
TI  - Growth and productivity impacts of periplasmic nuclease expression in an
      Escherichia coli Fab' fragment production strain.
AB  - Host cell engineering is becoming a realistic option in whole bioprocess
      strategies to maximize product manufacturability. High molecular weight (MW)
      genomic DNA currently hinders bioprocessing of Escherichia coli by causing
      viscosity in homogenate feedstocks. We previously showed that co-expressing
      Staphylococcal nuclease and human Fab' fragment in the periplasm of E. coli
      enables auto-hydrolysis of genomic DNA upon cell disruption, with a consequent
      reduction in feedstock viscosity and improvement in clarification performance.
      Here we report the impact of periplasmic nuclease expression on stability of DNA
      and Fab' fragment in homogenates, host-strain growth kinetics, cell integrity at
      harvest and Fab' fragment productivity. Nuclease and Fab' plasmids were shown to
      exert comparable levels of growth burden on the host W3110 E. coli strain.
      Nuclease co-expression did not compromise either the growth performance or
      volumetric yield of the production strain. 0.5 g/L Fab' fragment (75 L scale) and
      0.7 g/L (20 L scale) was achieved for both unmodified and cell-engineered
      production strains. Unexpectedly, nuclease-modified cells achieved maximum Fab'
      levels 8-10 h earlier than the original, unmodified production strain. Scale-down
      studies of homogenates showed that nuclease-mediated hydrolysis of high MW DNA
      progressed to completion within minutes of homogenization, even when homogenates
      were chilled on ice, with no loss of Fab' product and no need for additional co
      factors or buffering.

PMID- 21898369
TI  - Enzyme precipitate coatings of glucose oxidase onto carbon paper for biofuel cell
      applications.
AB  - Enzymatic biofuel cells (BFC) have a great potential as a small power source, but
      their practical applications are being hampered by short lifetime and low power
      density. This study describes the direct immobilization of glucose oxidase (GOx)
      onto the carbon paper in the form of highly stable and active enzyme
      precipitation coatings (EPCs), which can improve the lifetime and power density
      of BFCs. EPCs were fabricated directly onto the carbon paper via a three-step
      process: covalent attachment (CA), enzyme precipitation, and chemical
      crosslinking. GOx-immobilized carbon papers via the CA and EPC approaches were
      used as an enzyme anode and their electrochemical activities were tested under
      the BFC-operating mode. The BFCs with CA and EPC enzyme anodes produced the
      maximum power densities of 50 and 250 uW/cm(2) , respectively. The BFC with the
      EPC enzyme anode showed a stable current density output of >700 uA/cm(2) at 0.18
      V under continuous operation for over 45 h. When a maple syrup was used as a fuel
      under ambient conditions, it also produced a stable current density of >10
      uA/cm(2) at 0.18 V for over 25 h. It is anticipated that the direct
      immobilization of EPC on hierarchical-structured electrodes with a large surface
      area would further improve the power density of BFCs that can make their
      applications more feasible.

PMID- 21898370
TI  - Mobile phase modifier effects in multimodal cation exchange chromatography.
AB  - This study examines protein adsorption behavior and the effects of mobile phase
      modifiers in multimodal chromatographic systems. Chromatography results with a
      diverse protein library indicate that multimodal and ion exchange resins have
      markedly different protein binding behavior and selectivity. NMR results
      corroborate the stronger binding observed for the multimodal system and provide
      insight into the structural basis for the observed binding behavior. Protein
      binding affinity and selectivity in multimodal and ion exchange systems are then
      examined using a variety of mobile phase modifiers. Arginine and guanidine are
      found to have dramatic effects on protein adsorption, yielding changes in
      selectivity in both chromatographic systems. While sodium caprylate leads to
      slightly weaker chromatographic retention for most proteins, certain proteins
      exhibit significant losses in retention in both systems. The presence of a
      competitive binding mechanism between the multimodal ligand and sodium caprylate
      for binding to ubiquitin is confirmed using STD NMR. Polyol mobile phase
      modifiers are shown to result in increased retention for weakly bound proteins
      and decreased retention for strongly bound proteins, indicating that the overall
      retention behavior is determined by a balance between changes in electrostatic
      and hydrophobic interactions. This work provides an improved understanding of
      protein adsorption and mobile phase modifier effects in multimodal
      chromatographic systems and sets the stage for future work to develop more
      selective protein separation systems.

PMID- 21898371
TI  - Smoking cessation telephone quitlines effective regardless of recruitment method.

PMID- 21898372
TI  - Exemestane is effective for the chemoprevention of breast cancer.

PMID- 21898373
TI  - Determining the optimal dose and schedule of sunitinib: some answers, more
      questions.

PMID- 21898374
TI  - Combination of targeted agents in metastatic renal cell carcinoma: a path forward
      or a dead-end street?

PMID- 21898375
TI  - Phase 1 trial of everolimus plus sunitinib in patients with metastatic renal cell
      carcinoma.
AB  - BACKGROUND: Simultaneous inhibition of the vascular epithelial growth factor
      (VEGF) and the mammalian target of rapamycin (mTOR) pathway may improve treatment
      response in advanced renal cell carcinoma (RCC). Everolimus, an oral mTOR
      inhibitor, and sunitinib, an oral tyrosine kinase inhibitor targeting VEGF, are
      standard agents in the management of metastatic RCC. METHODS: Sequential cohorts
      of 3 to 6 patients with advanced RCC received dose-escalated combinations of
      sunitinib (37.5 or 50 mg daily, 4 weeks on/2 weeks off) with everolimus (2.5-5 mg
      daily or 20-30 mg weekly). Dose-limiting toxicities (DLTs) were assessed in the
      first 6-week cycle to determine maximum tolerated dose (MTD). Pharmacokinetic
      profiles were obtained. RESULTS: Twenty patients (13 clear cell and 7 nonclear
      cell RCC) were enrolled in 5 cohorts. Daily everolimus was not tolerated when
      combined with sunitinib; the first 2 patients on the second cohort suffered DLTs.
      With weekly everolimus, the MTD was 30 mg everolimus on days 7, 14, 21, and 28,
      plus 37.5 mg sunitinib on days 1 to 28 of a 42-day cycle; however, chronic
      treatment was associated with grade 3 and 4 toxicities. A schedule of 20 mg
      everolimus weekly/37.5 mg sunitinib was tolerated as chronic therapy. Five
      patients (25%) had confirmed partial responses, and 3 had nonclear cell RCC. No
      unexpected accumulation of everolimus, sunitinib, or N-desethyl sunitinib was
      observed. CONCLUSIONS: The combination of everolimus and sunitinib is associated
      with significant acute and chronic toxicities and is only tolerated at attenuated
      doses. Responses were observed in nonclear cell and clear cell RCC.

PMID- 21898376
TI  - Phase II trial of continuous once-daily dosing of sunitinib as first-line
      treatment in patients with metastatic renal cell carcinoma.
AB  - BACKGROUND: Sunitinib at 50 mg/day on the 4-weeks-on-2-weeks-off schedule is the
      current approved regimen for advanced/metastatic renal cell carcinoma (mRCC).
      Escudier et al reported that continuous, once-daily dosing with sunitinib 37.5 mg
      had a manageable safety profile and significant antitumor activity as second-line
      mRCC therapy. In this prospective, multicenter, phase II study, we evaluated the
      activity of continuous once-daily dosing with sunitinib 37.5 mg as first-line
      mRCC treatment. METHODS: One hundred nineteen treatment-naive patients with
      measurable mRCC received sunitinib. The primary endpoint was objective response;
      secondary endpoints included progression-free survival (PFS), safety,
      pharmacokinetic measurements, exploration of response biomarkers, and patient
      reported outcomes (PRO). RESULTS: Objective response rate (ORR) was 35.3%; median
      response duration was 10.4 months; 36% of patients had stable disease >=12 weeks.
      Median PFS at 1 year was 9 months, and 1-year survival probability was 67.8%. The
      most common any-grade treatment-related adverse events (AEs) were diarrhea (50%)
      and hand-foot syndrome (43%); the most common grade 3-4 treatment-related AEs
      were hand-foot syndrome (13%), neutropenia (11%), and diarrhea (9%). Steady-state
      pharmacokinetics were reached within 3 weeks, with no disproportionate
      accumulation of sunitinib or its active metabolite throughout the study. No
      significant correlations between trough drug, active metabolite, or soluble
      protein levels and clinical response were observed. PRO was largely maintained,
      although fatigue appeared to worsen after treatment started, with improvement
      over time. CONCLUSIONS: Continuous once-daily dosing with sunitinib 37.5 mg was
      active with a manageable safety profile as first-line mRCC therapy, making this a
      feasible alternative dosing regimen.

PMID- 21898377
TI  - Dysfunctional transforming growth factor-beta signaling with constitutively
      active notch signaling in Barrett's esophageal adenocarcinoma.

PMID- 21898379
TI  - Improvement of racial disparities with respect to the utilization of minimally
      invasive radical prostatectomy in the United States.
AB  - BACKGROUND: Race represents an established barrier to health care access in the
      United States and elsewhere. We examined whether race affects the utilization
      rate of minimally invasive radical prostatectomy (MIRP) in a population-based
      sample of individuals from the United States. METHODS: Within the Healthcare Cost
      and Utilization Project Nationwide Inpatient Sample (NIS), we focused on patients
      in whom MIRP and open radical prostatectomy (ORP) were performed between 2001 and
      2007. We assessed the proportions and temporal trends in race distributions
      between MIRP and ORP. Multivariable logistic regression analyses further adjusted
      for age, year of surgery, baseline Charlson Comorbidity Index, annual hospital
      caseload tertiles, hospital region, insurance status, and median zip code income.
      RESULTS: Of 65,148 radical prostatectomies, 3581 (5.5%) were MIRPs. African
      Americans accounted for 11.4% of patients versus 78.8% for Caucasians versus 9.9%
      for others. Between 2001 and 2007, the annual proportions of Caucasian patients
      treated with MIRP were 2.2%, 0.9%, 2.6%, 7.2%, 4.7%, 9.3%, and 11.6%,
      respectively (chi-square trend p<0.001). For the same years in African American
      patients, the proportions were 0.8, 0.3, 1.4, 4.4, 3.5, 9.0 and 8.4% (chi-square
      trend P < .001). In multivariable analyses relative to Caucasian patients,
      African American patients were 14% less likely to undergo MIRP (P = .01). After
      period stratification between years 2001-2005 versus 2006-2007, African Americans
      were 22% less likely to undergo a MIRP in the early period (P = .007) versus 11%
      less likely to have a MIRP in the contemporary period (P = .1). CONCLUSIONS: The
      racial discrepancies in MIRP utilization rates are gradually improving.

PMID- 21898380
TI  - Visualizing the dynamic of adoptively transferred T cells during the rejection of
      large established tumors.
AB  - Adoptive T-cell therapy (ATCT) can result in tumor rejection, yet the behavior
      and fate of the introduced T cells remain unclear. We developed a novel
      bioluminescence mouse model, which enabled highly sensitive detection of T-cell
      signals at the single-cell level. Transferred T cells preferentially accumulated
      within antigen-positive tumors, relative to the unaffected areas in each mouse,
      and remarkably, expanded within both lymphopenic and P14 mice. This expansion was
      controlled and efficient, as evaluated by bioluminescence imaging (BLI) of the T
      cell signals and by tumor rejection respectively. Analysis of the population
      dynamics of transferred T cells in ATCT of large tumors revealed that
      proliferation did not always follow a simple linear pattern of expansion, but
      showed an oscillating pattern of expansion and contraction that was often
      followed by a rebound, until full tumor rejection was achieved. Furthermore,
      visualizing the recall response showed that the transferred T cells responded
      expeditiously, indicating the ability of these cells to survive, establish memory
      and compete with endogenous T cells for as long as 1 year after rejecting the
      tumor.

PMID- 21898381
TI  - Bone morphogenetic proteins inhibit CD40L/IL-21-induced Ig production in human B
      cells: differential effects of BMP-6 and BMP-7.
AB  - Bone morphogenetic proteins (BMPs) are members of the TGF-beta superfamily. TGF
      beta can affect class switch recombination in human B cells, but whether BMPs
      also play a role have not been tested. We investigated the functional effects of
      exogenously added BMPs on CD27(-)  naive and CD27(+)  memory B cells from healthy
      donors. BMP-2, -4, -6 and -7 inhibited CD40L/IL-21-induced production of IgM, IgG
      and IgA. BMP-6 reduced Ig production by 70% in memory B cells and more than 55%
      in naive B cells, whereas the other BMPs were slightly less potent. We observed a
      striking difference in functional effects between the structurally similar BMP-6
      and BMP-7, as BMP-6 mainly inhibited plasmablast differentiation, and BMP-7
      mainly induced apoptosis. In memory B cells, BMP-6 upregulated expression of DNA
      binding protein inhibitor genes, but potently inhibited CD40L/IL-21-induced
      upregulation of the transcription factor XBP1, necessary for the late stages of
      plasmacytic differentiation. Expression of transcription factors regulating
      earlier stages (IRF4, PRDM1) was not affected by BMP-6. Taken together, these
      results show that BMPs are potent suppressors of naive and memory B cells.

PMID- 21898382
TI  - Peptide transporter TAP mediates between competing antigen sources generating
      distinct surface MHC class I peptide repertoires.
AB  - We recently described a category of TAP-independent peptide-epitopes that are
      selectively presented by cells with processing defects in the classical MHC class
      I (MHC-I) pathway. Here, we studied the ER-resident ceramide synthase Trh4 as a
      prototypic example of these neo-antigens and found that moderate inhibition of
      TAP permits cell surface presentation of the Trh4 peptide. The absence of this
      peptide from WT cells was not related to the binding or stability of the
      Trh4/D(b)  complexes, or to the availability of MHC-I heavy chains, but rather to
      the limited expression of the antigen. Strongly elevated antigen levels were
      needed to reach comparable peptide display on WT as on TAP-deficient cells. Our
      data suggest that the normal influx of TAP-transported peptides in the ER during
      routine processing creates an efficient barrier for peptides from alternative
      processing routes. Impairment of TAP function, as commonly found in cancers and
      virus-infected cells, lowers this resistance allowing for MHC-I presentation of
      other peptide sources.

PMID- 21898384
TI  - Surveillance of women at increased risk of breast cancer using mammography and
      clinical breast examination: further evidence of benefit.
AB  - Women with a significant family history of breast cancer are generally offered
      early surveillance by mammography and often clinical breast examination (CBE).
      The evidence base for surveillance has been questioned. We reviewed its
      effectiveness in terms of tumour size, lymph node status and survival in 7,475
      women seen over a 22-year period in the Manchester Family History Clinic. We
      diagnosed 139 invasive and 26 in situ breast cancers. Seventy-six percent of the
      invasive cancers were screen detected, 65% node negative and 71% <2 cm in
      diameter at diagnosis. Twenty-one tumours were BRCA1 positive and were
      significantly more likely to be grade 3, ER/PR negative (p < 0.0001) and have a
      poorer survival. CBE contributed to 30% of cancer diagnoses and was responsible
      for discovery of nine mammographically occult tumours. The cost per quality life
      year was estimated at L13,080 for tumours detected by CBE and not by mammography.
      We conclude that screening by annual mammography and CBE between age 35-50 years
      and 18 monthly from 50 to 60 years may diagnose breast cancer in a less advanced
      state in terms of size and node status compared with symptomatic cancers and,
      apart from BRCA1 carriers, is likely to contribute to improved long-term outcome
      compared with no surveillance.

PMID- 21898383
TI  - Increase in circulating levels of IGF-1 and IGF-1/IGFBP-3 molar ratio over a
      decade is associated with colorectal adenomatous polyps.
AB  - High levels of circulating insulin-like growth factor-1 (IGF-1) have been
      associated with increased risk of several cancers. Regarding colorectal cancer,
      these associations are generally weak. We hypothesized that an increase in IGF-1
      over time would be a stronger risk factor for cancer-related outcomes than the
      actual levels. In this analysis we utilized existing data from the Insulin
      Resistance and Atherosclerosis Study (IRAS). Circulating IGF-1 levels and molar
      ratios of IGF-1 to IGF binding protein 3 (IGFBP-3) were measured at three time
      points, within a 10-year follow-up period. We examined the associations of
      increase of the two variables with the presence of colorectal adenoma at the end
      of follow-up among participants with normal glucose tolerance at baseline. This
      included 143 individuals, from which 24 were diagnosed with adenomatous polyps.
      Although the mean levels of IGF-1 and IGF-1/IGFBP-3 decline with age, ~ 30% of
      the participants showed an increase of at least fifteen percent ("ever increase")
      in one or both of these variables, compared to baseline. We found a positive
      association between "ever increase" in IGF-1 or IGF-1/IGFBP-3 and the presence of
      colorectal adenoma: ORs were 3.81 (95% CI: 1.30-10.8) and 2.83 (95% CI: 1.00
      8.22), respectively. No association was found when analyzing the actual levels of
      both variables at any time point. Our data suggest that an increase in
      circulating IGF-1 or IGF-1/IGFBP-3 may represent a disturbed GH/IGF1 homeostasis,
      which could favor the development of precancerous lesions such as colorectal
      adenoma.

PMID- 21898385
TI  - Morbidity and mortality in gynecological cancers among first- and second
      generation immigrants in Sweden.
AB  - We studied the effect of new environment on the risk in and mortality of
      gynecological cancers in first- and second-generation immigrants in Sweden. We
      used the nationwide Swedish Family-Cancer Database to calculate standardized
      incidence/mortality ratios (SIRs/SMRs) of cervical, endometrial and ovarian
      cancers among immigrants in comparison to the native Swedes. Risk of cervical
      cancer increased among first-generation immigrants with Danish (SIR = 1.64),
      Norwegian (1.33), former Yugoslavian (1.21) and East European (1.35) origins,
      whereas this risk decreased among Finns (0.88) and Asians (SIRs varies from 0.11
      in Iranians to 0.54 in East Asians). Risk of endometrial (SIRs varies from 0.28
      in Africans to 0.86 in Finns) and ovarian (SIRs varies from 0.23 in Chileans to
      0.82 in Finns) cancers decreased in first-generation immigrants. The overall
      gynecological cancer risk for the second-generation immigrants, independent of
      the birth region, was almost similar to that obtained for the first generations.
      The birth region-specific SMRs of gynecological cancers in first- and second
      generation immigrants co-varied with the SIRs. Risk of gynecological cancers
      among the first-generation immigrants is similar to that in their original
      countries, except for cervical cancer among Africans and endometrial cancer among
      North Americans and East Europeans. Our findings show that risk and mortality of
      gynecological cancers observed in the first-generation immigrants remain in the
      second generation. We conclude that the risk and protective factors of
      gynecological cancers are preserved upon immigration and through generations,
      suggesting a role for behavioral factors or familial aggregation in the etiology
      of these diseases.

PMID- 21898386
TI  - mTOR as a therapeutic target in patients with gastric cancer.
AB  - The poor long-term outcomes associated with current chemotherapy treatment of
      patients with advanced gastric cancer suggest a need for novel targeted agents
      that may confer a better survival benefit. Evidence of mammalian target of
      rapamycin (mTOR) activation has been demonstrated in patient-derived gastric
      cancer cells and tumors. This review explores the relevance of the mTOR pathway
      to gastric cancer pathogenesis and its potential as a therapeutic target in
      patients with gastric cancer as well as presenting the first available clinical
      data on mTOR inhibitors in this disease setting. Preclinical data suggest that
      suppression of the mTOR pathway inhibited the proliferation of gastric cancer
      cells and delayed tumor progression in in vitro and animal models. In the
      clinical setting, the mTOR inhibitor everolimus has been active and well
      tolerated in phase I/II studies of patients with chemotherapy-refractory
      metastatic gastric cancer. Based on these promising results, everolimus currently
      is being investigated as a monotherapy or in combination with chemotherapeutic
      agents in ongoing phase II/III clinical studies.

PMID- 21898387
TI  - Validation of tumor-associated macrophage ferritin light chain as a prognostic
      biomarker in node-negative breast cancer tumors: A multicentric 2004 national
      PHRC study.
AB  - Novel prognostic biomarkers are imperatively needed to help direct treatment
      decisions by typing subgroups of node-negative breast cancer patients. Large
      screening of different biological compartments, such as the proteome, by means of
      high throughput techniques may greatly help scientists to find such markers. The
      present retrospective multicentric study included 268 node-negative breast cancer
      patients. We used a proteomic approach of SELDI-TOF-MS screening to identify
      differentially expressed cytosolic proteins with prognostic impact. The screening
      cohort was composed of 198 patients. Seventy supplementary patients were included
      for validation. Immunohistochemistry (IHC) and immunoassay (IA) were run to
      confirm the prognostic role of the marker identified by SELDI-TOF-MS screening.
      IHC was also used to explore links between selected marker and epithelial
      mesenchymal transition (EMT)-like, proliferation and macrophage markers. Ferritin
      light chain (FTL) was identified as an independent prognostic marker (HR = 1.30
      95% CI: 1.10-1.50, p = 0.001). Validation step by means of IHC and IA confirmed
      the prognostic value of FTL level. CD68 IHC showed that FTL was stored in tumor
      associated macrophages (TAM), which exhibit an M2-like phenotype. We report here,
      first, the validation of FTL as a breast tumor prognostic biomarker in node
      negative patients, and second, the fact that FTL is stored in TAM.

PMID- 21898388
TI  - Microsatellite instability in sporadic gastric cancer: its prognostic role and
      guidance for 5-FU based chemotherapy after R0 resection.
AB  - This study investigated whether MSI status can be used as a prognostic biomarker
      and whether it is helpful for predicting which patients will benefit from 5-FU
      based adjuvant chemotherapy. Between 2005 and 2008, an MSI status examination was
      performed in 1,990 gastric cancer patients who had undergone curative gastrectomy
      for gastric adenocarcinoma. MSI was analyzed by PCR amplification with
      fluorescent dye-labeled primers of mononucleotide markers (BAT25 and BAT26) and
      dinucleotide markers (D5S346, D2S123 and D17S250) specific to the microsatellite
      loci. Patients with MSI-H tumors accounted for 8.5% (n = 170) of the total study
      population. They tended to be older and female and to have distal tumor location,
      lower tumor stage, intestinal type of Lauren classification and differentiated
      histological type. The disease-free survival curves showed no significant
      differences between MSS/MSI-L and MSI-H patients at each stage of I, II, III and
      IV. In gastric cancer patients with stage II and III, 5-FU-based adjuvant
      chemotherapy showed better disease-free survival in the MSS/MSI-L group, but
      showed no benefits in the MSI-H group. By multivariate analysis, patients with
      MSS/MSI-L tumors benefited from 5-FU-based adjuvant chemotherapy in terms of
      tumor disease-free survival. MSI status in gastric cancer is not itself a
      prognostic indicator. However, it appears to be a possible guidance for the use
      of 5-FU-based chemotherapy in stage II and III gastric cancers after R0
      resection.

PMID- 21898389
TI  - Cost-effectiveness of KRAS testing in metastatic colorectal cancer patients in
      the United States and Germany.
AB  - The objective of this study was to determine the cost-effectiveness of testing
      for KRAS mutations before administering EGFR inhibitors such as cetuximab and
      panitumumab for patients with advanced metastatic colorectal cancer (mCRC) in the
      United States and Germany. We developed a lifetime Markov model of costs and
      survival associated with treating mCRC patients to assess the impact of KRAS
      testing before administering EGFR inhibitor-containing chemotherapy regimens.
      Overall, combination therapies involving cetuximab plus irinotecan/FOLFIRI had a
      better life expectancy (25.83 weeks) than cetuximab or panitumumab alone. Use of
      KRAS testing (assuming KRAS mutant patients receive only irinotecan) was equally
      effective and saved $12,428 per patient in the United States. When KRAS mutant
      patients received best supportive care, the life expectancy decreased slightly
      (24.26 weeks vs. 25.83 weeks) and the costs decreased by $13,501 in the United
      States and ?9,560 in Germany. For patients treated with cetuximab alone, use of
      KRAS testing to identify mutations lowered costs by $8,040 per patient in the
      U.S. analysis and ?3,856 per patient in the German analysis. For patients treated
      with panitumumab alone, use of KRAS testing to identify mutations lowered costs
      by $7,546 per patient in the U.S. analysis and ?4,612 per patient in the German
      analysis. Model results were sensitive to the cost of chemotherapy regimens and
      the prevalence of KRAS mutations in the population. Under most scenarios, using
      KRAS testing to select patients for EGFR inhibitor therapy saved $7,500-$12,400
      per patient in the United States and ?3,900-?9,600 per patient in Germany with
      equivalent clinical outcomes.

PMID- 21898390
TI  - A prospective, population-based study of 40,000 women regarding host factors, UV
      exposure and sunbed use in relation to risk and anatomic site of cutaneous
      melanoma.
AB  - Prospective cohort studies about cutaneous melanoma (CM) risk are still few. Host
      factor- and UVR exposure data were collected prospectively by questionnaire in
      this population-based cohort study including 40,000 Swedish born women, aged 25
      64 years at enrolment (1990). Risk for CM (Cox regression and Stepwise Cox
      regression [SCR], hazard ratios [HRs] with 95% Confidence Intervals [CI]) in
      relation to risk factors, age groups (older or younger than 40 years) and primary
      site, were analyzed. In 29,520 women with complete follow-up through 2007, 155
      invasive and 60 in situ CM were recorded. High numbers of nevi (HR, 2.9; 95% CI,
      1.7-5.0) and heredity (HR, 3.7; 95% CI, 2.0-6.8) were associated with risk for
      CM. SCR analysis added red hair as a risk factor. Sunbed use >10 times/year
      increased risk for women <40 years (HR, 2.5; 95% CI, 1.0-6.2) and a trend for
      risk associated with sunbathing vacations (HR, 1.4; 95% CI, 1.0-2.0) was shown
      for women >40 years. Trunk melanoma showed correlations with high numbers of nevi
      (HR, 3.0; 95% CI, 1.2-7.3) and heredity (HR, 3.2; 95% CI, 1.1-9.4). Head/neck
      site was correlated to sunbathing vacations (HR, 2.5; 95% CI, 1.2-5.3) and
      heredity (HR, 7.6; 95% CI, 1.8-31.8). Our study supports divergent etiologic
      pathways to CM, with high numbers of nevi correlated to increased risk for trunk
      CM. Furthermore, it confirms that high numbers of nevi, red hair and heredity for
      CM are the most important risk factors and frequent sunbed use might be a risk
      factor for younger women.

PMID- 21898391
TI  - Tumor lactic acidosis suppresses CTL function by inhibition of p38 and JNK/c-Jun
      activation.
AB  - Lactic acidosis is common to most solid tumors and has been found to affect
      infiltrating immune cells. Here we document effector phase inhibition of
      cytotoxic T cells (CTLs) involving complete blockage of cytokine production and
      partial impairment of lytic granule exocytosis. Lactic acidosis impaired TCR
      triggered phosphorylation of JNK, c-Jun and p38, while not affecting MEK1 and
      ERK. The select targeting of signaling proteins involved in IFNgamma production
      (JNK/c-Jun, p38) without affecting those jointly used in cytokine regulation and
      granule exocytosis (MEK1/ERK) explains the observed split effect of lactic
      acidosis on the CTL responses. CTL inhibition by lactic acidosis showed fast
      dynamics with immediate onset and reversion. Functional recovery by neutralizing
      the extracellular pH despite continuous presence of lactate holds promise that
      CTL activity can be improved in the milieu of solid tumors with appropriate anti
      acidosis treatment, thereby increasing the efficacy of adoptive T cell therapy.

PMID- 21898392
TI  - The restoration of myeloid-derived suppressor cells as functional antigen
      presenting cells by NKT cell help and all-trans-retinoic acid treatment.
AB  - Myeloid-derived suppressor cells (MDSCs), which accumulate during tumor
      progression, have been shown to function as important suppressor cells. In a
      previous study, we showed that immunosuppressive MDSCs could function as
      immunogenic antigen-presenting cells (APCs) with the help of activated natural
      killer T (NKT) cells. In the current study, however, we found that MDSCs
      harvested at a late time point after tumor injection (late MDSCs) were poorly
      immunogenic even when stimulated with activated NKT cells. As tumor growth
      progressed, the expression of MHC and costimulatory molecules on MDSCs was
      gradually down-regulated. Late MDSCs also had innate defects in activation and
      differentiation mediated by cytokine stimuli. Although late MDSCs treated only
      with all-trans-retinoic acid (ATRA), a stimulating agent for MDSC
      differentiation, could not become immunogenic, NKT ligand-loaded, ATRA-treated
      late MDSCs could be converted into immunogenic APCs to induce incremental immune
      responses. Furthermore, these effects were mediated by NKT cells secreting
      IFNgamma, and ATRA-mediated increases in glutathione (GSH) levels. Thus, combined
      treatment with differentiating and activating agents is a prerequisite for the
      conversion of late MDSCs into immunogenic APCs. Collectively, these results
      suggest that combined treatments are required for the differentiation and
      activation of late MDSCs in late stage cancer.

PMID- 21898393
TI  - Eradication of large tumors expressing human papillomavirus E7 protein by
      therapeutic vaccination with E7 fused to the extra domain a from fibronectin.
AB  - Cervical carcinoma is one of the most common cancers in women worldwide. It is
      well established that chronic infection of the genital tract by various
      mucosatropic human papillomavirus (HPV) types causes cervical cancer. Cellular
      immunity to E7 protein from HPV (HPVE7) has been associated with clinical and
      cytologic resolution of HPV-induced lesions. Thus, we decided to test if
      targeting of HPVE7 to dendritic cells using a fusion protein containing the extra
      domain A (EDA) from fibronectin, a natural ligand for TLR4, and HPVE7 (EDA-HPVE7)
      might be an efficient vaccine for the treatment of cervical carcinoma. We found
      that EDA-HPVE7 fusion protein was efficiently captured by bone marrow derived
      dendritic cells in vitro and induced their maturation, with the upregulation of
      maturation markers and the production of IL-12. Immunization of mice with EDA
      HPVE7 fusion protein induced antitumor CD8(+)  T cell responses in the absence of
      additional adjuvants. Repeated intratumoral administration of EDA-HPVE7 in saline
      was able to cure established TC-1 tumors of 5-7 mm in diameter. More importantly,
      intravenous injection with EDA-HPVE7 in combination with the TLR ligand
      polyinosinic-polycytidylic acid (pIC), or with low doses of cyclophosphamide and
      the TLR9 ligand CpG-B complexed in cationic lipids, were able to eradicate large
      established TC-1 tumors (1.2 cm in diameter). Thus, therapeutic vaccination with
      EDA-HPVE7 fusion protein may be effective in the treatment of human cervical
      carcinoma.

PMID- 21898394
TI  - Autocrine abscisic acid mediates the UV-B-induced inflammatory response in human
      granulocytes and keratinocytes.
AB  - UV-B is an abiotic environmental stress in both plants and animals. Abscisic acid
      (ABA) is a phytohormone regulating fundamental physiological functions in plants,
      including response to abiotic stress. We previously demonstrated that ABA is an
      endogenous stress hormone also in animal cells. Here, we investigated whether
      autocrine ABA regulates the response to UV-B of human granulocytes and
      keratinocytes, the cells involved in UV-triggered skin inflammation. The
      intracellular ABA concentration increased in UV-B-exposed granulocytes and
      keratinocytes and ABA was released into the supernatant. The UV-B-induced
      production of NO and of reactive oxygen species (ROS), phagocytosis, and cell
      migration were strongly inhibited in granulocytes irradiated in the presence of a
      monoclonal antibody against ABA. Moreover, presence of the same antibody strongly
      inhibited release of NO, prostaglandin E2 (PGE(2)), and tumor necrosis factor
      alpha (TNF-alpha) by UV-B irradiated keratinocytes. Lanthionine synthetase C-like
      protein 2 (LANCL2) is required for the activation of the ABA signaling pathway in
      human granulocytes. Silencing of LANCL2 in human keratinocytes by siRNA was
      accompanied by abrogation of the UV-B-triggered release of PGE(2), TNF-alpha, and
      NO and ROS production. These results indicate that UV-B irradiation induces ABA
      release from human granulocytes and keratinocytes and that autocrine ABA
      stimulates cell functions involved in skin inflammation.

PMID- 21898395
TI  - Selective cleavage of ErbB4 by G-protein-coupled gonadotropin-releasing hormone
      receptor in cultured hypothalamic neurons.
AB  - Gonadotropin-releasing hormone (GnRH) is secreted from hypothalamic neurons (GnRH
      neurons). GnRH neurons have a GnRH receptor belonging to the G-protein-coupled
      receptors. The stimulation of this receptor activates extracellular signal
      regulated kinase (ERK). In the present study, we found that epidermal growth
      factor receptor (EGFR) and ErbB4 were expressed in immortalized GnRH neurons (GT1
      7 cells). AG1478, a relatively specific inhibitor of the ErbB family, and small
      interfering RNA (siRNA) for ErbB4 inhibited the GnRH-induced activation of ERK in
      GT1-7 cells, suggesting that EGFR and ErbB4 were necessary for the activation. In
      addition, GnRH induced the cleavage of ErbB4 and accumulation of an 80-kDa
      fragment. After treatment of the cells with 50 nM GnRH for 5 min, about 80% of
      ErbB4 was cleaved. Biotinylation of cell surface proteins revealed that more than
      70% of the cell surface ErbB4 was cleaved by GnRH treatment. A higher
      concentration and longer treatment were necessary for GnRH to induce ErbB4
      cleavage than ERK activation. TAPI-2, an inhibitor of tumor necrosis factor-alpha
      converting enzyme (TACE), and siRNA for TACE inhibited the cleavage of ErbB4,
      suggesting that TACE was involved. After ErbB4 cleavage, the activation of ERK by
      neuregulin 1 was almost completely inhibited. These results suggest that the down
      regulation of ErbB4 expression is induced by G-protein-coupled receptor
      stimulation.

PMID- 21898396
TI  - Effects of moderate electrical stimulation on reactive species production by
      primary rat skeletal muscle cells: cross talk between superoxide and nitric oxide
      production.
AB  - The effects of a moderate electrical stimulation on superoxide and nitric oxide
      production by primary cultured skeletal muscle cells were evaluated. The
      involvement of the main sites of these reactive species production and the
      relationship between superoxide and nitric oxide production were also examined.
      Production of superoxide was evaluated by cytochrome c reduction and
      dihydroethidium oxidation assays. Electrical stimulation increased superoxide
      production after 1 h incubation. A xanthine oxidase inhibitor caused a partial
      decrease of superoxide generation and a significant amount of mitochondria
      derived superoxide was also observed. Nitric oxide production was assessed by
      nitrite measurement and by using 4,5-diaminofluorescein diacetate (DAF-2-DA)
      assay. Using both methods an increased production of nitric oxide was obtained
      after electrical stimulation, which was also able to induce an increase of iNOS
      content and NF-kappaB activation. The participation of superoxide in nitric oxide
      production was investigated by incubating cells with DAF-2-DA in the presence or
      absence of electrical stimulation, a superoxide generator system (xanthine
      xanthine oxidase), a mixture of NOS inhibitors and SOD-PEG. Our data show that
      the induction of muscle contraction by a moderate electrical stimulation protocol
      led to an increased nitric oxide production that can be controlled by superoxide
      generation. The cross talk between these reactive species likely plays a role in
      exercise-induced maintenance and adaptation by regulating muscular glucose
      metabolism, force of contraction, fatigue, and antioxidant systems activities.

PMID- 21898397
TI  - Estrogen controls embryonic stem cell proliferation via store-operated calcium
      entry and the nuclear factor of activated T-cells (NFAT).
AB  - Embryonic stem cells (ESCs) can self-renew indefinitely and differentiate into
      all cell lineages. Calcium is a universal second messenger which regulates a
      number of cellular pathways. Previous studies showed that store-operated calcium
      channels (SOCCs) but not voltage-operated calcium channels are present in mouse
      ESCs (mESCs). In this study, store-operated calcium entry (SOCE) was found to
      exist in mESCs using confocal microscopy. SOCC blockers lanthanum, 2
      aminoethoxydiphenyl borate (2-APB) and SKF-96365 reduced mESC proliferation in a
      concentration-dependent manner, suggesting that SOCE is important for ESC
      proliferation. Pluripotent markers, Sox-2, Klf-4, and Nanog, were down-regulated
      by 2-APB, suggesting that self-renewal property of mESCs relies on SOCE. 17beta
      estradiol (E2) enhanced mESC proliferation. This enhanced proliferation was
      associated with an increment of SOCE. Both stimulated proliferation and increased
      SOCE could be reversed by SOCC blockers suggesting that E2 mediates its
      stimulatory effect on proliferation via enhancing SOCE. Also, cyclosporin A and
      INCA-6, inhibitors of calcineurin [phosphatase that de-phosphorylates and
      activates nuclear factor of activated T-cells (NFAT)], reversed the proliferative
      effect of E2, indicating that NFAT is involved in E2-stimulated proliferation.
      Interestingly, E2 caused the nuclear translocation of NFATc4, and this could be
      reversed by 2-APB. These results suggested that NFATc4 is the downstream target
      of E2-induced SOCE. The present investigation provides the first line of evidence
      that SOCE and NFAT are crucial for ESCs to maintain their unique characteristics.
      In addition, the present investigation also provides novel information on the
      mechanisms of how E2, an important female sex hormone, affects ESC proliferation.

PMID- 21898398
TI  - CCN3 increases BMP-4 expression and bone mineralization in osteoblasts.
AB  - The nephroblastoma overexpressed (NOV) gene, also called CCN3, regulates
      differentiation of skeletal mesenchymal cells. Bone morphogenetic proteins (BMPs)
      play important roles in osteoblast differentiation and bone formation, but the
      effects of CCN3 on BMP expression and bone formation in cultured osteoblasts are
      largely unknown. Here we found that CCN3 increased BMP-4 expression and bone
      nodule formation in cultured osteoblast. Monoclonal antibodies for alpha5beta1
      and alphavbeta5 integrins, and inhibitors of integrin-linked kinase (ILK), p38,
      and JNK, all inhibited CCN3-induced bone nodule formation and BMP-4 up-regulation
      of osteoblasts. CCN3 stimulation increased the kinase activity of ILK and
      phosphorylation of p38 and JNK. Inhibitors of activator protein-1 (AP-1) also
      suppressed bone nodule formation and BMP-4 expression enhanced by CCN3. Moreover,
      CCN3-induced c-Jun translocation into the nucleus, and the binding of c-Jun to
      the AP-1 element on the BMP-4 promoter were both inhibited by specific inhibitors
      of the ILK, p38, and JNK cascades. Taken together, our results provide evidence
      that CCN3 enhances BMP-4 expression and bone nodule formation in osteoblasts, and
      that the integrin receptor, ILK, p38, JNK, and AP-1 signaling pathways may be
      involved.

PMID- 21898399
TI  - Niflumic acid blocks native and recombinant T-type channels.
AB  - Voltage-dependent calcium channels are widely distributed in animal cells,
      including spermatozoa. Calcium is fundamental in many sperm functions such as:
      motility, capacitation, and the acrosome reaction (AR), all essential for
      fertilization. Pharmacological evidence has suggested T-type calcium channels
      participate in the AR. Niflumic acid (NA), a non-steroidal anti-inflammatory drug
      commonly used as chloride channel blocker, blocks T-currents in mouse
      spermatogenic cells and Cl(-) channels in testicular sperm. Here we examine the
      mechanism of NA blockade and explore if it can be used to separate the
      contribution of different Ca(V)3 members previously detected in these cells.
      Electrophysiological patch-clamp recordings were performed in isolated mouse
      spermatogenic cells and in HEK cells heterologously expressing Ca(V)3 channels.
      NA blocks mouse spermatogenic cell T-type currents with an IC(50) of 73.5 uM,
      without major voltage-dependent effects. The NA blockade is more potent in the
      open and in the inactivated state than in the closed state of the T-type
      channels. Interestingly, we found that heterologously expressed Ca(V)3.1 and
      Ca(V)3.3 channels were more sensitive to NA than Ca(V)3.2 channels, and this drug
      substantially slowed the recovery from inactivation of the three isoforms.
      Molecular docking modeling of drug-channel binding predicts that NA binds
      preferentially to the extracellular face of Ca(V)3.1 channels. The biophysical
      characteristics of mouse spermatogenic cell T-type currents more closely resemble
      those from heterologously expressed Ca(V)3.1 channels, including their
      sensitivity to NA. As Ca(V)3.1 null mice maintain their spermatogenic cell T
      currents, it is likely that a novel Ca(V)3.2 isoform is responsible for them.

PMID- 21898400
TI  - miR-520c and miR-373 upregulate MMP9 expression by targeting mTOR and SIRT1, and
      activate the Ras/Raf/MEK/Erk signaling pathway and NF-kappaB factor in human
      fibrosarcoma cells.
AB  - MicroRNA 520c and 373 (miR-520c and miR-373) have been characterized as oncogenes
      and play critical roles in cancer cell metastasis. However, the relationship
      between these two microRNAs and matrix metalloproteinases (MMPs), which are
      important in cancer cell metastasis, remains unknown. Here, we report new
      evidence in which miR-520c and miR-373 effects in human fibrosarcoma HT1080 cells
      are associated with MMP9 activity, and this upregulation of MMP9 is not only at
      the activity and protein levels, but also at that of its mRNA. Our experimental
      data demonstrate that these effects occur not by direct binding to the MMP9
      promoter, but by miR-520c and miR-373 directly targeting the 3'-untranslational
      region (UTR) of mRNAs of mTOR and SIRT1 (negative regulators of expression of
      MMP9 via inactivating the Ras/Raf/MEK/Erk signaling pathway and transcription
      factor NF-kappaB activity); and thus suppressing translation levels of SIRT1 and
      mTOR. Moreover, inhibition of key kinases of the Ras/Raf/MEK/Erk signaling
      pathway and Western blots for selected proteins further identified miR-520c and
      miR-373 as activating this signaling pathway and NF-kappaB. In conclusion, miR
      520c and miR-373 increased the expression of MMP9 by directly targeting the 3'
      UTRs of mRNAs of mTOR and SIRT1 and suppressing their translation; resulting in
      activation of the Ras/Raf/MEK/Erk signaling pathway and NF-kappaB; and, finally,
      increasing the mRNA, protein, and activity of MMP9 and enhancing cell migration
      and cell growth in 3D type I collagen gels.

PMID- 21898401
TI  - Glycogen synthase kinase-3beta is critical for interferon-alpha-induced serotonin
      uptake in human Jurkat T cells.
AB  - Dysregulation of glycogen synthase kinase (GSK)-3beta contributes to the
      pathophysiology of mood disorders. However, how its regulation is responsible for
      the functioning of serotonin (5-HT) requires further investigation. Although
      enhancement of T-cell function may present an alternative strategy to treat
      depression, the precise mechanisms have yet to be established. Our previous
      studies have found that interferon-alpha (IFN-alpha) up-regulates serotonin
      transporter (5-HTT) expression and induces 5-HT uptake in T cells. The present
      study is to examine GSK-3beta regulation on IFN-alpha-induced 5-HTT functions.
      GSK-3beta short hairpin RNAs (shRNAs) or GSK-3beta inhibitors decreased IFN-alpha
      induced 5-HT uptake and 5-HTT expression. Src activation and calcium/calcium
      activated calmodulin kinase II (CaMKII) were involved in IFN-alpha-induced
      phosphorylation of proline-rich tyrosine kinase 2 (Pyk2) (Tyr402) and GSK-3beta
      (Tyr216), which regulated 5-HT uptake. GSK-3beta knockdown blocked the IFN-alpha
      induced phosphorylation of extracellular signal-regulated kinase (ERK) 1/2
      (Thr202/Tyr204) and signal transducer and transactivator (STAT) 1. In addition to
      inhibiting ERK, a selective 5-HTT inhibitor fluoxetine blocked IFN-alpha-induced
      activations of Src, CaMKII-regulated Pyk2/GSK-3beta cascade, as well as STAT1
      activation and translocation. These results indicated that calcium/CaMKII- and
      Src-regulated Pyk2 participated in IFN-alpha-induced GSK-3beta activation and GSK
      3beta-regulated 5-HT uptake. GSK-3beta signaling facilitated IFN-alpha-activated
      STAT1 by regulating ERK1/2, which controlled 5-HT uptake. Fluoxetine interfered
      with the Pyk2/GSK-3beta cascade, thereby inhibiting IFN-alpha-induced 5-HT
      uptake.

PMID- 21898402
TI  - Differential effect of CCL2 on constitutive neutrophil apoptosis between normal
      and asthmatic subjects.
AB  - In this study, we investigated the effects of CCL2 on constitutive apoptosis of
      normal and asthmatic neutrophils. CCL2 blocked the constitutive apoptosis of
      normal neutrophils through CCR2. CCL2 also induced elevation of the cytosolic
      Ca(2+) concentration but had no effect on normal neutrophil chemotaxis.
      Constitutive apoptosis, calcium influx, and cell migration of asthmatic
      neutrophils were not affected by CCL2 stimulation. Supernatant collected from
      CCL2-treated normal neutrophils inhibited the constitutive apoptosis of normal
      neutrophils. Anti-apoptotic signaling mediated by CCL2 was found to be associated
      with the PI3K/Akt/ERK/NF-kappaB cascade in normal neutrophils. Both the cleavage
      of procaspase 3 and procaspase 9 and the decrease of in Mcl-1 expression were
      delayed by CCL2 stimulation. Inhibition of NF-kappaB blocked constitutive
      apoptosis of neutrophils from asthmatic patients via inhibition of the cleavage
      of procaspase 3 and procaspase 9, in contrast to normal neutrophils. NF-kappaB
      was involved in CCL2-induced anti-apoptotic signaling in normal neutrophils,
      whereas NF-kappaB functioned as a basal pro-apoptotic factor in asthmatic
      neutrophils. A better understanding of the difference in the regulation of
      neutrophil apoptosis due to CCL2 between normal individuals and asthmatics will
      enable elucidation of the role of CC chemokine in neutrophils and a framework for
      understanding the pathogenesis of asthma.

PMID- 21898403
TI  - MC1R expression in HaCaT keratinocytes inhibits UVA-induced ROS production via
      NADPH oxidase- and cAMP-dependent mechanisms.
AB  - Ultraviolet A (UVA) radiations are responsible for deleterious effects, mainly
      due to reactive oxygen species (ROS) production. Alpha-melanocyte stimulating
      hormone (alpha-MSH) binds to melanocortin-1 receptor (MC1R) in melanocytes to
      stimulate pigmentation and modulate cutaneous inflammatory responses. MC1R may be
      induced in keratinocytes after UV exposure. To investigate the effect of MC1R
      signaling on UVA-induced ROS (UVA-ROS) production, we generated HaCaT cells that
      stably express human MC1R (HaCaT-MC1R) or the Arg151Cys (R(151)C) non-functional
      variant (HaCaT-R(151)C). We then assessed ROS production immediately after UVA
      exposure and found that: (1) UVA-ROS production was strongly reduced in HaCaT
      MC1R but not in HaCaT-R(151)C cells compared to parental HaCaT cells; (2) this
      inhibitory effect was further amplified by incubation of HaCaT-MC1R cells with
      alpha-MSH before UVA exposure; (3) protein kinase A (PKA)-dependent NoxA1
      phosphorylation was increased in HaCaT-MC1R compared to HaCaT and HaCaT-R(151)C
      cells. Inhibition of PKA in HaCaT-MC1R cells resulted in a marked increase of ROS
      production after UVA irradiation; (4) the ability of HaCaT-MC1R cells to produce
      UVA-ROS was restored by inhibiting epidermal growth factor receptor (EGFR) or
      extracellular signal-regulated kinases (ERK) activity before UVA exposure. Our
      findings suggest that constitutive activity of MC1R in keratinocytes may reduce
      UVA-induced oxidative stress via EGFR and cAMP-dependent mechanisms.

PMID- 21898404
TI  - IFNbeta impairs extracellular matrix formation leading to inhibition of
      mineralization by effects in the early stage of human osteoblast differentiation.
AB  - Osteoimmunology is an emerging field of research focused on the interaction of
      the immune system and bone. In this study we demonstrate that human osteoblasts
      are sensitive to the immune cytokine interferon (IFN)beta. Osteoblasts respond to
      IFNbeta as shown by the induction of several known IFN target genes such as
      interferon-induced (IFI) proteins (IFIT1, IFI44L), interferon-stimulated gene
      factor 3 (ISGF3) complex and the induction of IFNbeta itself. We demonstrated
      that IFNbeta has severe inhibitory effects on mineralization of osteoblast
      derived extracellular matrix (ECM). Analysis of the timing of the IFNbeta effects
      revealed that committed osteoblasts in early stage of differentiation are most
      sensitive to IFNbeta inhibition of mineralization. A single IFNbeta treatment was
      as effective as multiple treatments. During the progress of differentiation
      osteoblasts become desensitized for IFNbeta. This pinpoints to a complex pattern
      of IFNbeta sensitivity in osteoblasts. Focusing on early osteoblasts, we showed
      that IFNbeta decreased gene expression of ECM-related genes, such as type I
      Collagen (COL1A1), fibronectin (FN1), fibullin (FBLN1), fibrillin (FBN2), and
      laminin (LAMA1). Additionally, ECM produced by IFNbeta-treated osteoblasts
      contained less collagen protein. IFNbeta stimulated gene expression of
      osteopontin (OPN), annexin2 (ANXA2), and hyaluronan synthase 1 (HAS1), which are
      important factors in the adhesion of hematopoietic stem cells (HSC) in the HSC
      niche. In conclusion, IFNbeta directly modifies human osteoblast function by
      inhibiting ECM synthesis eventually resulting in delayed bone formation and
      mineralization and induces a HSC niche supporting phenotype. These effects are
      highly dependent on timing of treatment in the early phase of osteoblast
      differentiation.

PMID- 21898405
TI  - Mechanism of T-oligo-induced cell cycle arrest in Mia-PaCa pancreatic cancer
      cells.
AB  - DNA oligonucleotides with sequence homology to human telomeric DNA (T-oligo)
      induce cell cycle arrest, followed by apoptosis, senescence, or autophagy in a
      human cancer cell type-specific manner. T-oligo has potential as a new
      therapeutic strategy in oncology because of its ability to target certain types
      of tumor cells while sparing normal ones. In the present study, we demonstrate
      the T-oligo-induced S-phase cell cycle arrest in four pancreatic cancer cell
      lines. To further contribute to the mechanistic understanding of T-oligo, we also
      identify cyclin dependent kinase 2 (cdk2) as a functional mediator in the T-oligo
      induced cell cycle arrest of pancreatic cancer cells. Ectopic expression of a
      constitutively active cdk2 mutant abrogates T-oligo-induced cell cycle arrest in
      these tumor cells while knockdown of cdk2 expression alone recapitulates the T
      oligo effect. Finally, we demonstrate the dispensability of T-oligo-induced
      ATM/ATR-mediated DNA damage response-signaling pathways, which have long been
      considered functional in the T-oligo signaling mechanism.

PMID- 21898407
TI  - RKIP and cellular motility.

PMID- 21898406
TI  - The transcription factor osterix (SP7) regulates BMP6-induced human osteoblast
      differentiation.
AB  - The transcription factor osterix (Sp7) is essential for osteoblastogenesis and
      bone formation in mice. Genome wide association studies have demonstrated that
      osterix is associated with bone mineral density in humans; however, the molecular
      significance of osterix in human osteoblast differentiation is poorly described.
      In this study we have characterized the role of osterix in human mesenchymal
      progenitor cell (hMSC) differentiation. We first analyzed temporal microarray
      data of primary hMSC treated with bone morphogenetic protein-6 (BMP6) using
      clustering to identify genes that are associated with osterix expression. Osterix
      clusters with a set of osteoblast-associated extracellular matrix (ECM) genes,
      including bone sialoprotein (BSP) and a novel set of proteoglycans, osteomodulin
      (OMD), osteoglycin, and asporin. Maximum expression of these genes is dependent
      upon both the concentration and duration of BMP6 exposure. Next we overexpressed
      and repressed osterix in primary hMSC using retrovirus. The enforced expression
      of osterix had relatively minor effects on osteoblastic gene expression
      independent of exogenous BMP6. However, in the presence of BMP6, osterix
      overexpression enhanced expression of the aforementioned ECM genes. Additionally,
      osterix overexpression enhanced BMP6 induced osteoblast mineralization, while
      inhibiting hMSC proliferation. Conversely, osterix knockdown maintained hMSC in
      an immature state by decreasing expression of these ECM genes and decreasing
      mineralization and hMSC proliferation. Overexpression of the osterix regulated
      gene OMD with retrovirus promoted mineralization of hMSC. These results suggest
      that osterix is necessary, but not sufficient for hMSC osteoblast
      differentiation. Osterix regulates the expression of a set of ECM proteins which
      are involved in terminal osteoblast differentiation.

PMID- 21898408
TI  - Depression and type 2 diabetes: cortisol pathway implication and investigational
      needs.
AB  - Depression and type 2 diabetes (T2D) are clinically associated and the causes of
      the association are still under investigation. We aimed at identifying what is
      known about the stress response and cortisol pathway and the clinical association
      of depression and T2D, and at hypothesizing the link of the association. In this
      review, we report independent studies on stress response, cortisol pathway,
      depression, T2D, and independent studies on stress and cortisol pathway in
      depression, and in T2D. We focus and integrate the stress and cortisol pathway
      hypothesis to explain the clinical association of depression and T2D. We
      hypothesize that the corticotropin-releasing hormone receptors are one of the
      missing linking factor of the cortisol pathway underlying the clinical
      association of depression and T2D. We state what studies are still needed to
      confirm or rule out our hypothesis.

PMID- 21898409
TI  - CD133 and CD44 cell surface markers do not identify cancer stem cells in primary
      human gastric tumors.
AB  - Emerging evidence suggests that tumors contain and are driven by a cellular
      component that displays stem cell properties, the so-called cancer stem cells
      (CSCs). CSCs have been identified in several solid human cancers; however, there
      are no data about CSCs in primary human gastric cancer (GC). By using CD133 and
      CD44 cell surface markers we investigated whether primary human GCs contain a
      cell subset expressing stem-like properties and whether this subpopulation has
      tumor-initiating properties in xenograft transplantation experiments. We examined
      tissues from 44 patients who underwent gastrectomy for primary GC. The
      tumorigenicity of the cells separated by flow cytometry using CD133 and CD44
      surface markers was tested by subcutaneous or intraperitoneum injection in
      NOD/SCID and nude mice. GCs included in the study were intestinal in 34 cases and
      diffuse in 10 cases. All samples contained surface marker-positive cells:
      CD133(+) mean percentage 10.6% and CD133(+)/CD44(+) mean percentage 27.7%,
      irrespective of cancer phenotype or grade of differentiation. Purified CD133(+)
      and CD133(+)/CD44(+) cells, obtained in sufficient number only in 12 intestinal
      type GC cases, failed to reproduce cancer in two mice models. However, the
      unseparated cells produced glandular-like structures in 70% of the mice
      inoculated. In conclusion, although CD133(+) and CD133(+)/CD44(+) were detectable
      in human primary GCs, they neither expressed stem-like properties nor exhibited
      tumor-initiating properties in xenograft transplantation experiments.

PMID- 21898410
TI  - Role of ecto-NTPDases on UDP-sensitive P2Y(6)  receptor activation during
      osteogenic differentiation of primary bone marrow stromal cells from
      postmenopausal women.
AB  - This study aimed at investigating the expression and function of uracil
      nucleotide-sensitive receptors (P2Y(2), P2Y(4), and P2Y(6)) on osteogenic
      differentiation of human bone marrow stromal cells (BMSCs) in culture. Bone
      marrow specimens were obtained from postmenopausal female patients (68 +/- 5
      years old, n = 18) undergoing total hip arthroplasty. UTP and UDP (100 uM)
      facilitated osteogenic differentiation of the cells measured as increases in
      alkaline phosphatase (ALP) activity, without affecting cell proliferation. Uracil
      nucleotides concentration-dependently increased [Ca(2+)](i) in BMSCs; their
      effects became less evident with time (7 > 21 days) of the cells in culture.
      Selective activation of P2Y(6) receptors with the stable UDP analog, PSB 0474,
      mimicked the effects of both UTP and UDP, whereas UTPgammaS was devoid of effect.
      Selective blockade of P2Y(6) receptors with MRS 2578 prevented [Ca(2+)](i) rises
      and osteogenic differentiation caused by UDP at all culture time points. BMSCs
      are immunoreactive against P2Y(2), P2Y(4), and P2Y(6) receptors. While the
      expression of P2Y(6) receptors remained fairly constant (7~21 days), P2Y(2) and
      P2Y(4) became evident only in less proliferative and more differentiated cultures
      (7 < 21 days). The rate of extracellular UTP and UDP inactivation was higher in
      less proliferative and more differentiated cell populations. Immunoreactivity
      against NTPDase1, -2, and -3 rises as cells differentiate (7 < 21 days). Data
      show that uracil nucleotides are important regulators of osteogenic cells
      differentiation predominantly through the activation of UDP-sensitive P2Y(6)
      receptors coupled to increases in [Ca(2+)](i) . Endogenous actions of uracil
      nucleotides may be balanced through specific NTPDases determining whether
      osteoblast progenitors are driven into proliferation or differentiation.

PMID- 21898411
TI  - Modulation of functional responses of endothelial cells linked to angiogenesis
      and inflammation by shear stress: differential effects of the mechanotransducer
      CD31.
AB  - We investigated the roles of the "mechanotransducer" CD31 in the effects of shear
      stress on endothelial gene expression and functional responses relevant to
      angiogenesis and inflammation. Human or murine endothelial cells (hEC or mEC)
      were exposed to different levels of shear stress, while expression of CD31 was
      modified using siRNA in the hEC, or mEC from CD31(-/-) mice. Quantitation of
      expression of genes linked to inflammation or angiogenesis showed several were
      sensitive to shear. In a "wound" assay, exposure of endothelial cells (EC) to
      shear stress tended to align migration with the direction of flow and decrease
      the rate of closure compared to static cultures. When EC were cultured on
      filters, shear stress promoted migration away from the luminal surface. EC
      conditioned by shear stress recruited fewer flowing neutrophils, and showed
      reduced up-regulation of E-selectin after stimulation with tumor necrosis factor
      alpha (TNF). Use of siRNA against CD31 in the hEC, or testing of mEC from mice
      lacking CD31, indicated that expression of CD31 was not required for the shear
      induced modification of wound closure. However, shear modulation of response to
      TNF was less effective in the absence of CD31, while reduction of CD31 reduced
      shear-sensitivity in some genes (e.g., eNOS), but not others (e.g., KLF-2). Thus,
      CD31 played a role in shear-sensitivity of some genes and of neutrophil
      recruitment, but not in modulation of endothelial migration. Different
      mechanotransducers may mediate different functional effects of shear stress.
      Hence, identification of the specific pathways may provide targets for
      therapeutic manipulation of angiogenesis or inflammation.

PMID- 21898412
TI  - RhoA/ROCK, cytoskeletal dynamics, and focal adhesion kinase are required for
      mechanical stretch-induced tenogenic differentiation of human mesenchymal stem
      cells.
AB  - Human bone marrow mesenchymal stem cells (hMSCs) have the potential to
      differentiate into tendon/ligament-like lineages when they are subjected to
      mechanical stretching. However, the means through which mechanical stretch
      regulates the tenogenic differentiation of hMSCs remains unclear. This study
      examined the role of RhoA/ROCK, cytoskeletal organization, and focal adhesion
      kinase (FAK) in mechanical stretch-induced tenogenic differentiation
      characterized by the up-regulation of tendon-related marker gene expression. Our
      findings showed that RhoA/ROCK and FAK regulated mechanical stretch-induced
      realignment of hMSCs by regulating cytoskeletal organization and that RhoA/ROCK
      and cytoskeletal organization were essential to mechanical stretch-activated FAK
      phosphorylation at Tyr397. We also demonstrated that this process can be blocked
      by Y-27632 (a specific inhibitor of RhoA/ROCK), cytochalasin D (an inhibitor of
      cytoskeletal organization) or PF 573228 (a specific inhibitor of FAK). The
      results of this study suggest that RhoA/ROCK, cytoskeletal organization, and FAK
      compose a "signaling network" that senses mechanical stretching and drives
      mechanical stretch-induced tenogenic differentiation of hMSCs. This work provides
      novel insights regarding the mechanisms of tenogenesis in a stretch-induced
      environment and supports the therapeutic potential of hMSCs.

PMID- 21898413
TI  - 4.1G promotes arborization and tight junction formation of oligodendrocyte cell
      line OLN-93.
AB  - 4.1G belongs to the membrane-associated band 4.1 protein family, which plays
      important roles in establishing and maintaining the links between transmembrane
      proteins and the cytoskeleton. Till date, expression and functions of 4.1G in the
      central nervous system (CNS) have not been fully elucidated. We investigated
      expression, cellular/subcellular distribution, and biological roles of 4.1G in
      the rat CNS and in cultured oligodendrocyte cell line OLN-93. Immunoblotting (IB)
      and immunoprecipitation revealed CNS 4.1G protein isoforms with molecular weights
      ranging from ~80 to ~180 kDa. In subconfluent OLN-93 cell culture, overexpression
      of full-length 4.1G and C-terminal-domain-deleted 4.1G, but not the FERM-domain
      deleted 4.1G, promoted cellular arborization. In confluent cells, endogenous 4.1G
      was upregulated and clustered in the cytoplasmic periphery together with tight
      junction protein ZO-1. FERM domain seemed essential for this recruitment of 4.1G
      to OLN-93 cell periphery. Calcium switch experiment demonstrated that
      overexpressed 4.1G promoted tight junction reassembly, whereas siRNA knockdown of
      endogenous 4.1G inhibited tight junction formation among confluent OLN-93 cells.
      Together, these results suggest functional roles of 4.1G in cellular arborization
      and tight junction formation. In the CNS, 4.1G might be involved in maturation of
      host cells as well as in interaction among neurons/neuroglia.

PMID- 21898414
TI  - Heparin-integrin interaction in endothelial cells: downstream signaling and
      heparan sulfate expression.
AB  - Endothelial cells (ECs) are a source of physiologically important molecules that
      are synthesized and released to the blood and/or to the subendothelial
      extracellular matrix such as a heparan sulfate proteoglycan (HSPG) with
      antithrombotic properties. Previously, we have shown that heparin stimulates the
      synthesis and modifies the sulfation pattern of this HSPG. Here the molecular
      mechanisms involved in the up-regulation of HSPG synthesis by heparin in
      endothelial cells were decoded. The cells were stimulated with heparin and the
      expression of HSPG and intracellular pathways were evaluated by a combination of
      methods involving confocal microscopy, flow cytometry, Western blotting analyses,
      and [(35) S]-sulfate metabolically labeling of the cells. We observed that the up
      regulation of HSPG synthesis evoked by heparin is dependent on the interaction of
      heparin with integrin since RGD peptide abolishes the effect. The activation of
      integrin leads to tyrosine-phosphorylation of focal adhesion-associated proteins
      such as FAK, Src, and paxillin. In addition, heparin induces ERK1/2
      phosphorylation and inhibitors of Ras and MEK decreased heparin-dependent HSPG
      synthesis. Moreover, heparin also induced intracellular Ca(2+) release, PLCgamma1
      (phospholipase Cgamma1) and CaMKII (calcium calmodulin kinase II) activation, as
      well as an increase in nitric oxide (NO) production. Finally, an intracellular
      Ca(2+) chelator, Ca(2+) signaling inhibitors, and an endothelial NO synthase
      inhibitor were all able to abolish the effect in heparan sulfate synthesis. In
      conclusion, the heparin-induced up-regulation of HSPG expression is associated
      with the phosphorylation of focal adhesion proteins and Ras/Raf/MEK/ERK MAP and
      Ca(2+) /NO pathways.

PMID- 21898415
TI  - Survival analysis of gastric cancer patients with tumor thrombus in the portal
      vein.
AB  - BACKGROUND: A tumor thrombus in the portal vein originating from gastric cancer
      is a rare condition. Little is known about the development of portal vein tumor
      thrombus (PVTT) and its effect on the survival of gastric cancer patients.
      METHODS: PVTT originating from gastric cancer was identified retrospectively with
      computed tomography in 51 patients, from January 2002 to June 2007. PVTT was
      classified by metastatic routes as follows: lymph node (LN), hepatic mass, and
      hematogenous type. The median survival from PVTT, and the factors affecting the
      survival of gastric cancer patients with PVTT were analyzed. RESULTS: The median
      survival of gastric cancer patients with PVTT (N = 51) was 5.4 months. The median
      survival was compared according to clinical characteristics, and multivariate
      analysis proved that female and hepatic mass type were independent risk factors
      for poor prognosis. The characteristics of the hepatic mass type were old age,
      higher proportion of tumors located in the upper-third of the stomach, and liver
      metastasis, compared to the LN or the hematogeneous type. CONCLUSIONS: PVTT
      originating from gastric cancer was a poor prognostic factor and the median
      survival from PVTT was different according to several clinical factors.

PMID- 21898416
TI  - Long-term results and prognostic factors of gastric cancer patients with only
      positive peritoneal lavage cytology.
AB  - BACKGROUND AND OBJECTIVES: The purpose of the present study was to investigate
      clinicopathologic features of gastric cancer patients with only positive
      peritoneal cytology in the absence of overt peritoneal metastases, and which
      might distinguish patients with poorer prognosis. METHODS: Between September 1994
      and August 2006, clinicopathological features were retrospectively evaluated in
      37 consecutive patients with gastric cancer who underwent a curative resection
      and had positive peritoneal cytology in the absence of overt peritoneal
      metastases. Survival including disease-free survival (DFS) and overall survival
      (OS), and recurrence patterns were analyzed according to clinicopathologic
      characteristics. RESULTS: The median follow-up period was 16.1 months (range, 3
      45 months). The median DFS and OS of patients after curative resection were 10
      months (range, 1-33 months) and 15 months (range, 2-45 months), respectively. All
      patients had recurred, in 34 (92%) with peritoneal dissemination. The overall 1-,
      2-, 3-, and 5-year survival rates for the 37 consecutive patients were 43.2%,
      45.9%, 5.4%, and 0%, respectively. Multiple linear regression analysis revealed
      that Borrmann type IV was an independent predictor for poorer prognosis.
      CONCLUSIONS: A Borrmann type IV carcinoma may be the candidates for
      intraperitoneal chemotherapy among advanced gastric cancer patients.

PMID- 21898417
TI  - B lymphocytes as effector cells in the immunotherapy of cancer.
AB  - Over the years, the role of B cells in the host immune response to malignancy has
      been overshadowed by our focus on T cells. Nevertheless, B cells play important
      roles as antigen-presenting cells and in the production of antibodies.
      Furthermore, B cells can function as effector cells that mediate tumor
      destruction on their own. This review will highlight the various functions of B
      cells that are involved in the host response to tumor.

PMID- 21898418
TI  - Large needle suction aspiration of permanent fillers.
AB  - Temporary injectable fillers have become so widely accepted within the cosmetic
      medical industry that permanent fillers with longer lasting effects are fast
      gaining popularity. Both patients and physicians alike have eagerly sought a
      product to minimize the inconvenience and cost of repeated injections. However,
      the fear is that the use of permanent fillers may lead to permanent problems. We
      describe here an in-office technique to remove permanent injectable fillers that
      achieves consistent, natural results with minimal risk of scarring.

PMID- 21898420
TI  - In reference to Acute airway obstruction in cervical spinal procedures with bone
      morphogenetic proteins.

PMID- 21898419
TI  - Medialization versus reinnervation for unilateral vocal fold paralysis: a
      multicenter randomized clinical trial.
AB  - PURPOSE: Vocal fold medialization laryngoplasty (ML) and laryngeal reinnervation
      (LR) as treatments for unilateral vocal fold paralysis (UVFP) were compared in a
      multicenter, prospective, randomized clinical trial. METHODS: Previously
      untreated patients with UVFP were randomized to undergo either ML or LR. Voice
      results were compared pretreatment and at 6 and 12 months posttreatment using
      perceptual ratings by untrained listeners (RUL), blinded speech pathologist GRBAS
      scores, and voice-related quality of life (VRQOL) scores. Other secondary data
      included maximum phonation time (MPT), cepstral analysis, and electromyography
      (EMG) findings. RESULTS: Twenty-four patients from nine sites completed the
      study, 12 in each group. There were no significant intergroup differences in
      pretreatment variables. At 12 months, both study groups showed significant
      improvement in RUL, total GRBAS (grade, roughness, breathiness, asthenia, and
      strain) scores, and VRQOL scores, but no significant differences were found
      between the two groups. However, patient age significantly affected the LR, but
      not the ML, group results. The age less than 52 LR subgroup had significantly (P
      < .05) better scores than the age more than 52 LR subgroup, and had better RUL
      and GRBAS scores than the age less than 52 ML subgroup. The age more than 52 ML
      subgroup results were significantly better than the age more than 52 LR subgroup.
      The secondary data generally followed the primary data, except that the MPTs for
      the ML patients were significantly longer than for the LR patients. CONCLUSIONS:
      ML and LR are both effective surgical options for patients with UVFP. Laryngeal
      reinnervation should be considered in younger patients, whereas medialization
      laryngoplasty should be favored in older patients.

PMID- 21898421
TI  - Effect of temporary vocal fold injection medialization on the rate of permanent
      medialization laryngoplasty in unilateral vocal fold paralysis patients.
AB  - OBJECTIVES/HYPOTHESIS: To determine whether temporary vocal fold injection
      affects the need for permanent medialization laryngoplasty in patients with
      unilateral vocal fold paralysis (UVFP). STUDY DESIGN: Retrospective chart review.
      METHODS: A total of 175 patients with dysphonia resulting from UVFP were
      identified. Patients with documented recovery of vocal fold mobility, <9 months
      of follow-up after diagnosis of UVFP, previous treatment at other institutions,
      neoplastic disease involving the larynx, or history of radiation to the larynx
      were excluded. Fifty-four patients met all inclusion/exclusion criteria. Rates of
      permanent medialization laryngoplasty in patients undergoing vocal fold injection
      were compared with those of patients who chose observation or voice therapy.
      RESULTS: A total of 35% of patients underwent temporary injection medialization,
      and the remaining 65% chose conservative management. Five of 19 of the temporary
      injection medialization patients subsequently underwent permanent intervention
      compared to 23 of 35 of the conservative management group (P = .0131).
      CONCLUSIONS: UVFP patients who underwent vocal fold injection with an agent
      intended to provide temporary medialization were statistically significantly less
      likely to undergo permanent medialization laryngoplasty compared to those
      patients who were treated with conservative management only.

PMID- 21898422
TI  - Evidence for distinct histologic profile of nasal polyps with and without
      eosinophilia.
AB  - OBJECTIVE/HYPOTHESIS: To evaluate the histology, RNA, and protein signatures of
      nasal polyps (NPs) in order to demonstrate specific subtypes of disease and
      differentiate "idiopathic" NPs based on tissue eosinophilia. STUDY DESIGN:
      Prospective laboratory-based study. METHODS: NP tissue was obtained from patients
      referred to the University of Virginia Health System for sinus surgery. Histology
      analyses included hematoxylin-eosin, Gomori's trichrome, toluidine blue, and
      chloroacetate staining. RNA and protein were extracted from tissue and cytokine
      transcript or protein concentrations determined. RESULTS: Idiopathic NPs can be
      divided into distinct subsets characterized by absence (NE) and presence (E) of
      prominent eosinophilia. The validity of this distinction is supported by the
      demonstration that NE polyps are further distinguished by glandular hypertrophy,
      dense collagen deposition, and mononuclear cellular infiltrate. In contrast, E-NP
      display edema, rare glandularity, and minimal collagen deposition except within
      the basement membrane. Total mast cell numbers were reduced in E-NP, whereas
      connective tissue mast cells were increased in NE-NP. Consistent with the
      distinctive pattern of increased fibrosis, NE-NP displayed increased transforming
      growth factor-beta and vascular endothelial growth factor transcripts. Similarly,
      NE-NPs had higher concentrations of transforming growth factor-beta, fibroblast
      growth factor-beta, and platelet-derived growth factor protein. CONCLUSIONS:
      Idiopathic NPs can be distinguished by NE and E and are supported by the
      observations that these display distinct histologic, gene, and protein expression
      patterns. The findings suggest that as unique diseases, idiopathic NPs will
      require distinct therapeutic interventions.

PMID- 21898423
TI  - Cultured vestibular ganglion neurons demonstrate latent HSV1 reactivation.
AB  - OBJECTIVES/HYPOTHESIS: Vestibular neuritis is a common cause of both acute and
      chronic vestibular dysfunction. Multiple pathologies have been hypothesized to be
      the causative agent of vestibular neuritis; however, whether herpes simplex type
      I (HSV1) reactivation occurs within the vestibular ganglion has not been
      demonstrated previously by experimental evidence. We developed an in vitro system
      to study HSV1 infection of vestibular ganglion neurons (VGNs) using a cell
      culture model system. STUDY DESIGN: basic science study. RESULTS: Lytic infection
      of cultured rat VGNs was observed following low viral multiplicity of infection
      (MOI). Inclusion of acyclovir suppressed lytic replication and allowed latency to
      be established. Upon removal of acyclovir, latent infection was confirmed with
      reverse-transcription polymerase chain reaction and by RNA fluorescent in situ
      hybridization for the latency-associated transcript (LAT). A total of 29% cells
      in latently infected cultures were LAT positive. The lytic ICP27 transcript was
      not detected by reverse-transcription polymerase chain reaction (RT-PCR).
      Reactivation of HSV1 occurred at a high frequency in latently infected cultures
      following treatment with trichostatin A (TSA), a histone deactylase inhibitor.
      CONCLUSIONS: VGNs can be both lytically and latently infected with HSV1.
      Furthermore, latently infected VGNs can be induced to reactivate using TSA. This
      demonstrates that reactivation of latent HSV1 infection in the vestibular
      ganglion can occur in a cell culture model, and suggests that reactivation of
      HSV1 infection a plausible etiologic mechanism of vestibular neuritis.

PMID- 21898424
TI  - T-cadherin in the mammalian cochlea.
AB  - OBJECTIVES/HYPOTHESIS: Cadherins are a superfamily of transmembrane
      glycoproteins, which mediate calcium-dependent intercellular adhesions. T
      cadherin is an atypical member of the cadherin family in regard to its structure;
      it acts as a signalling receptor rather than an adhesion molecule. In this study
      we examine the role of T-cadherin in the mammalian cochlea. STUDY DESIGN: This
      study investigated the expression of T-cadherin in the inner ear under
      physiologic and pathologic conditions. METHODS: Expression of T-cadherin in the
      rat cochlea was analyzed by reverse-transcriptase polymerase chain reaction (RT
      PCR), real-time RT-PCR, Western blot, and immunohistochemistry. RESULTS: We
      detected T-cadherin mRNA expression in three different components in the cochlea
      of postnatal mouse, namely the organ of Corti (OC), the spiral ganglion (SG), and
      the stria vascularis (SV). The SG and SV showed a higher T-cadherin mRNA level
      than the OC. T-cadherin protein was detected by Western blotting in the OC, SG,
      and SV. Immunofluorescence microscopy of adult mouse cochlea revealed the
      presence of T-cadherin in the apical parts of the inner and outer hair cells as
      well as in the SV and SG. OCs treated with gentamicin for 3, 6, or 12 hours did
      not show any change in T-cadherin gene expression compared to control explants
      maintained in culture medium alone. CONCLUSIONS: T-cadherin is expressed within
      the cochlea. T-cadherin seems to have a wide variety of functions in the inner
      ear, ranging from mechanical functions to functions in response to hair cell
      damage and loss.

PMID- 21898425
TI  - Ventilatory techniques for central airway obstruction.

PMID- 21898426
TI  - Clinical experience in diagnosis and management of superior semicircular canal
      dehiscence in children.
AB  - OBJECTIVES/HYPOTHESIS: To identify clinical characteristics of pediatric superior
      semicircular canal dehiscence (SSCD) and explore suitable options of management.
      STUDY DESIGN: Retrospective review. METHODS: The study comprised 10 patients with
      auditory and/or vestibular symptoms suspicious for SSCD. One patient pursued care
      at another institution, and two did not return for follow-up. Subsequently, seven
      patients (11 ears, 6 females and 1 male, aged 5-11 years) were included. Patients
      were evaluated using high-resolution temporal bone computed tomography. Those
      suspected of having SSCD underwent vestibular evoked myogenic potential testing
      for confirmation in addition to routine audiologic tests. RESULTS: All seven
      patients had auditory and/or vestibular impairment. Auditory symptoms included
      autophony, tinnitus, and conductive or mixed hearing loss. Bone conduction
      responses were occasionally better than 0 dB HL. Vestibular dysfunction included
      vertigo, often in response to loud noises, and chronic disequilibrium. One
      patient underwent surgical repair for disabling vestibular symptoms with dramatic
      improvement in both auditory and vestibular symptoms postoperatively. The
      remaining six were closely monitored with routine exams. CONCLUSIONS: In contrast
      to adults, children with SSCD usually present with auditory symptoms first,
      although they share some similarities with adults in clinical manifestations of
      SSCD. Our study shows that SSCD syndrome, a well-accepted clinical entity, exists
      in the pediatric population. Conservative management is preferred for children
      with SSCD; nevertheless, surgical intervention is necessary for those with
      disabling vestibular symptoms. To date, this is the first clinical case series of
      symptomatic pediatric patients with SSCD.

PMID- 21898427
TI  - Toward safer practice in otology: a report on 15 years of clinical negligence
      claims.
AB  - OBJECTIVES/HYPOTHESIS: To determine the characteristics of medical negligence
      claims arising from otological practice. STUDY DESIGN: Retrospective analysis of
      medical negligence claims contained in the National Health Service Litigation
      Authority (NHSLA) database. METHODS: Claims relating to otology and neurotology
      between 1995 and 2010 were obtained from the NHSLA database and analyzed for
      cause of injury, type of injury, outcome of claim and costs. RESULTS: Over 15
      years there were 137 claims in otology, representing 26% of all the claims in
      otolaryngology. Of these, 116 have been closed, and 84% of closed claims resulted
      in payment. Of the 97 successful claims, 63 were related to operative
      complications. This included six cases of wrong side/site surgery, and 15 cases
      of inadequate informed consent. The most common injuries claimed were hearing
      loss, facial paralysis, and additional/unnecessary surgery. Middle ear
      ventilation and mastoid surgery were the procedures most commonly associated with
      a successful claim. There were 15 successful claims of misdiagnosis/delayed
      diagnosis, with chronic suppurative otitis media the condition most frequently
      missed. There were nine successful claims related to outpatient procedures, of
      which seven were for aural toilet and six claims of medical mismanagement,
      including three cases of ototoxicity from topical medications. There were also
      four successful claims for morbidity due to delayed surgery. CONCLUSIONS: This is
      the first study to report outcomes of negligence claims in otology. Claims in
      otology are associated with a high success rate. A significant proportion of
      claims are not related to surgery and represent areas where safety should also be
      addressed.

PMID- 21898428
TI  - Partial cricotracheal resection with tracheal intussusception and cricoarytenoid
      joint mobilization: early experience in a new technical variant.

PMID- 21898429
TI  - Central segment harvest of costal cartilage in rhinoplasty.
AB  - OBJECTIVES/HYPOTHESIS: Our objective was to review our experience with a
      conservative central boat harvest of costal cartilage in patients undergoing
      rhinoplasty. It involves taking only the central portion of the rib for
      reconstruction. When cartilage harvest is performed in the above manner, donor
      site morbidity is minimized without limiting aesthetic results. The key seems to
      be preservation of intact costal cartilage on three sides, limiting harvest to
      the central portion only. This central portion is straight and much less prone to
      warping than the cartilage toward the periphery. STUDY DESIGN: A retrospective
      review of a single surgeon's experience. METHODS: All rhinoplasty operations
      performed by the senior author (Y.D.) from January 2000 to August 2009 that
      required the harvest of rib cartilage were reviewed. RESULTS: A total of 322
      cases were identified in which rib cartilage was harvested via the described
      technique. In all cases sufficient cartilage volume was obtained for the intended
      purpose. Average operation time was 10 minutes. No drains were used, and only one
      patient developed seroma formation. Postoperative pain and scar were minimal. No
      major complications were noted, and on postoperative analysis there was no
      evidence of cartilage warping or displacement. CONCLUSIONS: When harvesting
      costal cartilage for rhinoplasty, the above technique allows for sufficient graft
      tissue while decreasing donor site morbidity and minimizing warping.

PMID- 21898430
TI  - Auditory brainstem response morphology and analysis in very preterm neonatal
      intensive care unit infants.
AB  - OBJECTIVES/HYPOTHESIS: Analysis of auditory brainstem response (ABR) in very
      preterm infants can be difficult owing to the poor detectability of the various
      components of the ABR. We evaluated the ABR morphology and tried to extend the
      current assessment system. STUDY DESIGN: Prospective cohort study. METHODS: We
      included 28 preterm very low birth weight infants admitted to the neonatal
      intensive care unit of Sophia Children's Hospital. ABRs were measured between 26
      and 34 weeks postconceptional age. The presence of the following ABR parameters
      was recorded: the ipsilateral peaks I, III and V, the contralateral peaks III and
      V, and the response threshold. RESULTS: In 82% of our population, a typical "bow
      tie" response pattern was present as a sign of early auditory development. This
      bow tie pattern is the narrowest part of the response wave and is predominantly
      characterized by the ipsilateral negative peak III. This effect may be emphasized
      by the contralateral peak III. The bow tie pattern is seen approximately 0.1
      milliseconds before the ipsilateral peak III. From 30 weeks postconceptional age
      onward, a more extensive morphologic pattern is recorded in 90% of the infants. A
      flow chart was designed to analyze the ABR morphology of preterm infants in an
      unambiguous stepwise fashion. CONCLUSIONS: A typical bow tie pattern preceding
      peak III seems to be the earliest characteristic of the developing ABR morphology
      in preterm infants. As ABR characteristics will improve with increasing age,
      neonatal hearing screening should be postponed until after 34 weeks.

PMID- 21898431
TI  - Evolution in the management of facial nerve schwannoma.
AB  - OBJECTIVE: To design a treatment algorithm based on experience with facial nerve
      schwannomas (FNS) over a 30-year period. STUDY DESIGN: Retrospective chart
      review. METHOD: Seventy-nine patients with facial nerve schwannomas seen from
      1979 through 2009 at a tertiary referral private otologic practice were
      categorized by treatment modality. Interventions included surgical resection with
      grafting, bony decompression, observation, or stereotactic radiation. Outcome
      measures included House-Brackmann facial nerve grade before and after
      intervention as well as change in facial nerve grade, tumor size, involved
      segments of nerve, time to intervention. RESULTS: Thirty-seven patients (46.8%)
      ultimately underwent surgical excision with grafting or primary anastomosis, 21
      (26.6%) underwent bony decompression alone, 15 (19.0%) were managed with
      observation only, and 6 (7.6%) had stereotactic radiation. Through 1995, 85% of
      cases had surgical resection and none had observation only. Of the 52 patients
      seen after 1995, 27% had surgical resection and grafting, 33% had bony
      decompression, 29% were managed with observation alone, and 11% had radiotherapy.
      Facial nerve grade was maintained or improved over the follow-up period (mean
      time = 3.9 years) in 78.9% of the decompression group and 100% of the observation
      and radiation groups compared to 54.8% of the resection group (P <= .012).
      CONCLUSIONS: Surgical resection and grafting, once widely accepted and practiced,
      has in many cases given way to observation, bony decompression, or stereotactic
      radiation. A wide armamentarium of options is available to the neurotologist
      treating facial nerve schwannomas with the ability to preserve facial function
      for a longer period of time.

PMID- 21898432
TI  - Injection of human mesenchymal stem cells improves healing of vocal folds after
      scar excision--a xenograft analysis.
AB  - OBJECTIVES: Using a xenograft model the aim was to analyze if injection of human
      mesenchymal stem cells (hMSC) into the rabbit vocal fold (VF), after excision of
      an established scar, can improve the functional healing of the VF. STUDY DESIGN:
      Prospective design with an experimental xenograft model. METHODS: The VFs of 12
      New Zealand rabbits were injured by a bilateral localized resection. After 9
      weeks the scar after the resection was excised and hMSC were injected into the
      VFs. After another 10 weeks 10 VFs were dissected and stained for histology.
      Lamina propria thickness and relative content of collagen type I were measured.
      Viscoelasticity of 14 VFs at phonatory frequencies was quantified by a simple
      shear rheometer. The hMSC survival was determined using a human DNA specific
      reference probe, that is, FISH analysis. RESULTS: The viscoelastic measurements,
      that is, dynamic viscosity and elastic shear modulus for the hMSC-treated VFs,
      were found to be similar to those of normal controls and were significantly lower
      than those of untreated controls (P < .05). A significant reduction in lamina
      propria thickness was also shown for the hMSC treated VFs compared with the
      untreated VFs (P < .05). This histologic finding corresponded with the
      viscoelastic results. No hMSC survived 10 weeks after the injection. CONCLUSIONS:
      Human mesenchymal stem cells injected into the rabbit VF following the excision
      of a chronic scar, were found to enhance the functional healing of the VF with
      reduced lamina propria thickness and restored viscoelastic shear properties.

PMID- 21898434
TI  - Cochlear implantation has a positive influence on quality of life, tinnitus, and
      psychological comorbidity.
AB  - OBJECTIVES: To determine the effect of cochlear implantation (CI) on health
      related quality of life (HRQoL), tinnitus, and psychological comorbidity in
      patients with severe to profound postlingual hearing loss and to analyze the
      relationship between these parameters. STUDY DESIGN: Prospective study. METHODS:
      Using six validated questionnaires, we evaluated the pre-CI and post-CI scores of
      HRQoL, tinnitus, perceived stress, symptoms of depression and anxiety, and coping
      strategies in 43 patients implanted unilaterally with a multichannel implant for
      at least 6 months. RESULTS: In addition to improvements in hearing, speech
      understanding, and disease-specific HRQoL, psychological comorbidity was reduced
      and coping strategies were improved following CI. In the 39 tinnitus patients,
      their tinnitus was reduced. We found negative correlations between HRQoL and
      stress, depression, and anxiety. Pre-CI, tinnitus severity did not correlate with
      HRQoL and psychological comorbidity. However, patients with a high-level tinnitus
      had lower HRQoL as well as a higher level of perceived stress and anxiety
      symptoms than patients with a low-level tinnitus and no/incidental tinnitus
      before CI. Moreover, patients with severe hearing loss had a higher level of
      perceived symptoms of stress and depression than patients with profound hearing
      loss before CI. CONCLUSIONS: The present study provides evidence that tinnitus
      and psychological comorbidity may play an important role in the rehabilitation of
      CI patients, and that there is a correlation between HRQoL and these parameters.
      In addition to hearing tests, tinnitus, stress, and psychological comorbidity
      should be assessed using validated questionnaires before and after CI. This will
      help to improve the rehabilitation process.

PMID- 21898433
TI  - Analysis of eIF4E and 4EBP1 mRNAs in head and neck cancer.
AB  - OBJECTIVES/HYPOTHESIS: The eukaryotic translation initiation factor 4E (eIF4E) in
      conjunction with its binding protein, 4EBP1, regulates the translation of cap
      dependent mRNAs. An aberrant increase in eIF4E shifts the balance in favor of
      translation of transcripts that promote cell proliferation and malignancy. eIF4E
      protein is commonly elevated in head and neck squamous cell carcinomas (HNSCC),
      and its overexpression is associated with increased recurrence. An underlying
      mechanism for eIF4E overexpression is gene amplification, and we wanted to
      determine whether eIF4E mRNA could serve as a prognostic maker of HNSCC. METHODS:
      Tumor specimens from 26 HNSCC patients and oral tissues from 17 control subjects
      were examined for eIF4E and 4EBP1 by semiquantitative RT-PCR and correlated with
      clinical and pathologic findings. RESULTS: Unlike eIF4E mRNA alone, expression of
      eIF4E relative to 4EBP1 was a more precise predictor of HNSCC and its progression
      (P < .01, Wilcoxon rank sum test). Eight of 26 patients (31%) had elevated
      eIF4E:4EBP1 (4E:4EBP1; >25), and 7 of these (87.5%) had recurrence. Alternately,
      from 18 patients with low 4E:4EBP1 (<25; 69%), only 5 patients had recurrence
      (30.1%). To determine the probability of no recurrence, Kaplan-Meier analysis
      showed significantly poor disease-free survival in patients with elevated
      4E:4EBP1 than those with low ratios (P < .01, log rank test). CONCLUSIONS:
      Elevated 4E:4EBP1 significantly correlated with increased disease recurrence.
      Because 4EBP1 modulates eIF4E activity, our results highlight the importance of
      incorporating a joint analysis of eIF4E and 4EBP1 mRNAs in HNSCC patient care
      decisions.

PMID- 21898435
TI  - ORL emergencies boot camp: using simulation to onboard residents.
AB  - OBJECTIVES/HYPOTHESIS: Incoming otolaryngology residents are expected to triage
      and manage airway, bleeding, and other emergencies with little prior experience.
      Simulation-based education has become increasingly important as it provides tools
      to develop psychomotor skills and judgment early in residency, using realistic
      experiences while eliminating patient risk. We hypothesize that a Boot Camp
      course emphasizing basic otolaryngology management will increase participants'
      confidence and be perceived as useful in developing their knowledge, technical
      skills, self-confidence, and improving clinical performance, both immediately and
      6 months following the course. STUDY DESIGN: Survey. METHODS: A 1-day Boot Camp
      was developed consisting of six technical skills stations (mask ventilation,
      intubation, flexible laryngoscopy, microlaryngoscopy/bronchoscopy, epistaxis
      control, and cricothyroidotomy); a session involving telephone inquiry triage,
      and two complex airway scenarios addressing medical management and emphasizing
      team leadership. Residents completed questionnaires before, immediately, and 6
      months following course completion. RESULTS: Thirty residents enrolled, 27
      participated in the course, and 24 completed all three surveys. Previous
      experiences and confidence levels were variable; 26 of 30 (87%) identified
      emergency airway management as a concern before attending the course. A Fisher's
      exact test demonstrated improved confidence (P < .05) for every skill. An
      overwhelming majority of participants agreed or strongly agreed the intervention
      was useful in developing their knowledge, technical skills, self-confidence, and
      improving clinical performance. CONCLUSIONS: An intensive, simulation-based Boot
      Camp addressing airway, bleeding, and other otolaryngology emergencies was
      successful in improving junior otolaryngology residents' confidence and was
      perceived as useful in developing knowledge, technical skills, self-confidence,
      and improving clinical performance.

PMID- 21898436
TI  - Acute supraglottitis in adults in Finland: review and analysis of 308 cases.
AB  - OBJECTIVE: The aim of this article is to study the clinical features, management,
      and outcome in adult patients with acute supraglottitis. STUDY DESIGN:
      Retrospective review. METHODS: We searched the medical records from our database
      from the years 1989 to 2009 using codes of international statistical
      classification of diseases and related health problems for acute epiglottitis or
      supraglottitis. In total, 308 patients were identified. RESULTS: Incidence of
      acute supraglottitis increased from 1.88 (first decade) to 4.73 per 100,000 cases
      (second decade) (P = .05). The mean age of the patients was 49 years old with a
      slightly male predominance. Sore throat and odynophagia were the most common
      symptoms. Concomitant disease were common among the patients. Isolated
      inflammation of epiglottis without involvement of other supraglottic tissue was
      detected only in 51 patients. Intravenous cephalosporins were the most common
      empiric antibiotic treatment regimen. Intravenous corticosteroids were
      administered to half of the cases. Streptococcus was the most common organism in
      throat cultures. In total, 45 patients needed airway intervention. Complications
      were rare and mortality was 0.6% in our series. CONCLUSIONS: Acute supraglottitis
      in adults seems to be a different entity than epiglottitis in children, and
      inflammation does not usually exclusively involve the epiglottis. Early diagnosis
      seems to decrease the need for airway intervention and to permit the successful
      treatment of the patient with intravenous antibiotics and corticosteroids.
      Streptococcus appears as the dominant causative microorganism. However systemic
      diseases and other local infections that compromise the regional supraglottic
      immunity may increase the risk for acute supraglottitis.

PMID- 21898438
TI  - Endoscopic laser-assisted diverticulotomy versus open surgical approach in the
      treatment of Zenker's diverticulum.
AB  - OBJECTIVES/HYPOTHESIS: This study aimed to evaluate the results of endoscopic
      laser-assisted diverticulotomy and the transcervical approach in treating
      Zenker's diverticulum. STUDY DESIGN: Retrospective clinical study. METHODS:
      Results of 155 cases after endoscopic laser-assisted diverticulotomy and the
      transcervical approach were retrospectively compared. RESULTS: Primary treatment
      consisted of endoscopic laser-assisted diverticulotomy in 65.2%, and 34.8% were
      treated by a transcervical approach. Average follow-up time was 61.8 months.
      Surgical time, duration of hospitalization, and occurrence of minor complications
      were significantly lower after endoscopic approach. Recurrence rate showed a
      statistically significant difference in favor of open approach. Including the
      recurrences, 38.7% could be cured only by transcervical techniques. Patient
      perception of success was found to be similar for the compared treatment
      modalities. CONCLUSIONS: Endoscopic approach proved to be the treatment of first
      choice. However, the fact that open techniques were necessary in nearly 40% of
      our cases suggests that this operative technique retains a substantial role in
      treatment of this disease.

PMID- 21898437
TI  - Otologic and audiologic manifestations of Hutchinson-Gilford progeria syndrome.
AB  - OBJECTIVES/HYPOTHESIS: To define the audiologic and otologic phenotype of
      Hutchinson-Gilford progeria syndrome (HGPS). STUDY DESIGN: Prospective case
      series. METHODS: Fifteen patients with HGPS were enrolled in a prospective
      natural history study; 14 were evaluated in the neurotology clinic, and 11
      received audiologic evaluations. The physical exam and audiologic findings of
      these patients were reviewed to define an otologic and audiologic phenotype for
      HGPS in the largest series of subjects in the literature. RESULTS: All patients
      were noted to have stiff auricular cartilages, small or absent lobules, and
      hypoplasia of the lateral soft-tissue portion of the external ear canal leading
      to a shortened canal. Ten of 14 patients (71%) had dry cerumen impaction, and
      four of 14 patients (29%) reported a history of recurrent otitis media. Nineteen
      of 22 ears (86.4%) demonstrated low-frequency conductive hearing loss in the 250
      to 500 Hz range. Sixteen of 22 ears (73%) had type A tympanograms; three of 22
      ears (14%) displayed bimodal or "W" peaked tympanograms; two of 22 ears (9%) had
      type B tympanograms; one of 22 ears (4%) had a type C tympanogram. Nine of 10
      patients had distortion product otoacoustic emissions consistent with normal
      peripheral hearing sensitivity. CONCLUSIONS: HGPS is caused by a mutation in the
      LMNA gene resulting in the production of an abnormal nuclear protein; this in
      turn affects nuclear structure and function. Patients with HGPS have
      characteristic otologic features due to cartilaginous and subcutaneous tissue
      abnormalities and typically demonstrate low-frequency conductive hearing loss
      despite largely normal tympanometry. It is important to be aware of these
      conditions in managing these patients.

PMID- 21898439
TI  - Augmented image guidance improves skull base navigation and reduces task workload
      in trainees: a preclinical trial.
AB  - OBJECTIVES/HYPOTHESIS: Our group has developed an augmented image guidance system
      that incorporates intraoperative cone-beam computed tomography (CBCT), virtual or
      augmented displays, and image registration. We assessed the potential benefits of
      augmented endoscopy derived from this system for use during skull base
      navigation. Specifically, we wished to evaluate target localization accuracy and
      the effect on task workload and confidence. STUDY DESIGN: Prospective,
      sequential, paired preclinical trial. METHODS: A single cadaver head underwent
      computed tomography, and critical structures were contoured. The specimen was
      reimaged after endoscopic dissection and deformable registration allowed contours
      to be displayed on postablation CBCT imaging. A real-time virtual view including
      anatomical contours was provided parallel to the real endoscopic image. Twelve
      subjects were asked to endoscopically localize seven skull base landmarks in a
      conventional manner. The same exercise was then performed with augmented
      endoscopy. Precise three-dimensional (3D) localization was recorded with a
      tracked probe. The NASA task load index was completed after each exercise. A
      short questionnaire was also administered. RESULTS: The real-time augmented image
      guidance system aided localization in 85% of responses and increased confidence
      in 97%. There was a significant reduction in mental demand, effort, and
      frustration when the technology was employed, with an increase in perceived
      performance (P < .05). Three dimensional navigational precision was improved for
      all landmarks. CONCLUSIONS: Real-time augmented image-guided surgery increases
      accuracy and confidence in trainee surgeons and decreases task workload during
      skull base navigation. This technology shows great promise in assisting in skull
      base surgery even for experienced surgeons.

PMID- 21898440
TI  - Nasal endoscopy in children with suspected allergic rhinitis.
AB  - OBJECTIVES/HYPOTHESIS: Ear, nose, and throat assessment may be frequently
      requested for children with allergic rhinitis (AR). Nasal endoscopy allows a
      thorough evaluation of the nose. The aim of the study was to investigate whether
      there are endoscopic signs predictive for AR diagnosis in a cohort of children
      with suspected AR. STUDY DESIGN: Cohort of observational study. METHODS: There
      were 176 children (99 males; mean age, 7.5 years) studied. Clinical visit, nasal
      endoscopy, and skin prick test were performed in all patients. Nasal endoscopic
      signs were pale turbinates, middle turbinate contact, and inferior turbinate
      contact. The AR diagnosis was made when nasal symptom history was concordant with
      sensitization. RESULTS: AR was diagnosed in 141 children. Inferior and middle
      turbinate contact were reliable predictive factors for AR (odds ratio 5.38 and
      3.42, respectively), whereas pale turbinates did not predict it. CONCLUSIONS:
      This study suggests that nasal endoscopy may reveal signs predictive for AR
      diagnosis in children.

PMID- 21898442
TI  - Anterior laryngofissure approach to an airway foreign body after migration into
      the paraglottic space.

PMID- 21898441
TI  - Acute stress to excised vocal fold epithelium from reactive oxygen species.
AB  - OBJECTIVES/HYPOTHESIS: Vocal fold epithelium is exposed to reactive oxygen
      species from the inhaled environment and from tissue inflammation. The objective
      of this study was to explore the functional and structural consequences of
      reactive oxygen species exposure on vocal fold epithelium. STUDY DESIGN: In
      vitro, prospective study design. METHODS: Hydrogen peroxide (H(2)O(2)), a common
      reactive oxygen species, was utilized in this study. Freshly excised, viable
      porcine vocal fold epithelia (N = 32) were exposed to H(2) O(2) or sham challenge
      for 2 hours. Electrophysiology, western blotting, and light microscopy were used
      to quantify the functional and structural effects of reactive oxygen species on
      vocal fold epithelia. RESULTS: Exposure to reactive oxygen species did not
      significantly alter transepithelial resistance. There was a small, nonsignificant
      trend for decreased concentration of epithelial junctional complex protein with
      reactive oxygen species challenge. Minimal changes to the gross structural
      appearance of vocal fold epithelia were also noted. CONCLUSIONS: The stratified
      squamous epithelia of the vocal folds effectively defend against an acute
      reactive oxygen species challenge. The current study lays the groundwork for
      future investigations on the effects of reactive oxygen species on vocal fold
      epithelia that are compromised from phonotrauma.

PMID- 21898443
TI  - Endoscopic transvestibular paramandibular exploration of the infratemporal fossa
      and parapharyngeal space: a minimally invasive approach to the middle cranial
      base.
AB  - OBJECTIVES/HYPOTHESIS: To describe a novel transvestibular endoscopic approach
      for the exposure, exploration, and resection of lesions in the infratemporal
      fossa (ITF) and parapharyngeal space (PPS). STUDY DESIGN: Surgical technique and
      clinical feasibilty of a novel approach to the middle cranial base. METHODS: The
      transvestibular endoscopic approach was applied to four patients with lesions
      involving the ITF and PPS. Through a vertical oral mucosal incision along the
      ascending ramus of the mandible, an optical corridor to the ITF and PPS was
      created and maintained with the aid of a Hardy speculum. The contents of the ITF
      and PPS were explored with the aid of a 0-degree 4-mm rigid endoscope. RESULTS:
      Four patients underwent exploration of their right-sided ITF and PPS. The
      approach provided exposure and access from the middle cranial base at the level
      of the foramen ovale to the mid-PPS. Branches of the trigeminal nerve in the ITF
      were safely explored and preserved. Exposure and visualization of the internal
      maxillary artery and branches were achieved. Of the four patients, two underwent
      resection of a primary and a recurrent pleomorphic adenoma, one had chronic pain
      relief from a large synovial chondromatosis, and one had debulking of a recurrent
      mucoepidermoid carcinoma. The only complications were self-limiting hypoesthesia
      of the lip in one patient and transient dysphagia in another patient.
      CONCLUSIONS: The transvestibular endoscopic approach to the ITF and PPS offers
      direct and minimally invasive access to select lesions within this region.
      Further use of this approach will allow us to determine its potential and
      limitations.

PMID- 21898444
TI  - Neck mass due to pedicle ossification after oromandibular reconstruction.
AB  - OBJECTIVES/HYPOTHESIS: To determine the radiographic incidence of heterotopic
      ossification and the clinical incidence of neck masses secondary to heterotopic
      ossification in a series of patients who underwent fibula free flap oromandibular
      reconstruction. STUDY DESIGN: Retrospective review at a university medical
      center. METHODS: Patient database of 520 consecutive fibula free flaps from 1995
      to 2010 was reviewed to identify patients who had postoperative computed
      tomography (CT) scans of the neck to further investigate the radiologic presence
      of heterotopic ossification. Patient chart review was also performed to identify
      patients who had clinical evidence of neck masses consistent with heterotopic
      ossification. RESULTS: Of the 66 patients who had postoperative CT scans
      available for radiologic assessment, 43 (65%) showed heterotopic ossification of
      the fibula periosteum. Clinically, 14 of 520 patients (2.6%) presented with firm,
      level I or II neck masses that proved to be secondary to heterotopic
      ossification. CONCLUSIONS: Development of a firm neck mass after treatment of
      head and neck cancer often indicates recurrent tumor. Heterotopic ossification
      has not been previously reported as a potential etiology of neck masses after
      fibula free flap oromandibular reconstruction in the head and neck surgery
      literature. The radiographic incidence of this phenomenon is high, and the
      clinical incidence of neck masses secondary to heterotopic ossification is low.
      Heterotopic ossification can be distinguished from recurrent tumor on the basis
      of physical examination, radiographic assessment, and/or fine-needle aspiration
      biopsy. Awareness of heterotopic ossification should be included in the
      differential diagnosis of patients with a neck mass who have undergone fibula
      free flap reconstructions.

PMID- 21898445
TI  - Incidence of revision adenoidectomy in children.
AB  - OBJECTIVE/HYPOTHESIS: Adenoidectomy is a frequently performed procedure in the
      pediatric population. Revision rates and indications for a second procedure in
      children are scarce. STUDY DESIGN: Retrospective cohort study. METHODS: Patient
      records at a multistate pediatric healthcare system were searched for all CPT
      codes that included adenoidectomy in children less than 12 years of age for a 5
      year period (2005-2010). A subset of patients was identified for whom the same
      CPT codes appeared more than once in this 5-year period. The indication, age,
      gender, adenoid size, and technique of adenoidectomy were recorded. RESULTS: A
      total of 23,612 occurrences of the CPT codes were identified. The subset of
      patients with multiple CPT codes, indicating revision adenoidectomy, included 304
      records (1.3%). Mean age at first procedure was 2.8 years (SD = 1.7 years). Mean
      age at second procedure was 4.7 years (SD = 1.99 years). Mean interval between
      procedures was 1.8 years (SD = 1.1 years). CONCLUSIONS: Revision adenoidectomy
      occurs at a rate of 1.3%. Reasons for revision include persistence symptoms
      ranging from adenoiditis to recurrent otitis to obstructive sleep apnea.

PMID- 21898446
TI  - Optimal timing of surgical intervention following adult laryngeal trauma.
AB  - OBJECTIVE: Laryngeal trauma is an infrequent diagnosis with a scarcity of
      published data. We aim to further define the factors associated with positive
      surgical outcomes of adult laryngeal trauma. STUDY DESIGN: Multi-institution
      database analysis. METHODS: Of the 1.9 million trauma cases from the National
      Trauma Database (NTDB), 564 adult trauma events were selected with ICD-9 codes
      specific to laryngeal trauma. RESULTS: Laryngeal trauma was seen predominately in
      white (61.5%), middle-aged (40.6 years), male (83.7%) patients experiencing blunt
      (70.7%) laryngeal injury with multiorgan system (92.2%) trauma. There was an
      overall 17.9% mortality rate. Within the 564 cases, 133 direct laryngoscopies,
      185 tracheostomies, 53 laryngeal suturing, and 60 laryngeal fracture repairs were
      performed. In univariate negative binomial regression models, trauma severity (P
      <= .01), placement of tracheostomy (P lt; .01), and delayed tracheostomy
      placement (P = .04, .03, .048) were associated with increased ventilator
      dependence, intensive care unit (ICU) stay, and overall hospital admission
      duration. Multivariate regression models demonstrated significant associations
      between tracheostomy performed within 24 hours and shortened ICU stay (P = .03,
      beta = -.28, SE = 1.7) and overall hospital stay (P = .009, beta = -.23, SE =
      3.1). CONCLUSIONS: The NTDB allows study of the largest laryngeal trauma cohort
      in modern literature. Although complexities arise in the treatment of laryngeal
      traumas, when indicated, surgical airway should be placed within 24 hours of
      presentation to improve the overall hospital course.

PMID- 21898447
TI  - Endoscopic endonasal transpterygoid nasopharyngectomy.
AB  - OBJECTIVE: Describe our technique for endoscopic transpterygoid nasopharyngectomy
      and support its feasibility with our early clinical outcomes. METHODS: Our
      endoscopic technique comprises an extended inferomedial maxillectomy,
      mobilization of the pterygopalatine fossa, removal of the pterygoid plates and
      Eustachian tube to access the posterolateral nasopharynx. Control of the
      parapharyngeal and petrous segments of the internal carotid artery is the
      keystone of the approach. RESULTS: Various histopathologies were treated,
      including epidermoid carcinomas (n = 9), lymphoepithelioma (n = 1), adenoid
      cystic carcinoma (n = 5), adenocarcinoma (n = 2), mucoepidermoid carcinoma (n =
      2), and sarcoma (n = 1). Negative microscopic margins were obtained in 95%
      (19/20) of patients. No perioperative mortality, cerebral spinal fluid (CSF)
      leak, meningitis, or cerebrovascular accident was encountered; however, one
      patient suffered an internal carotid artery (ICA) injury, without permanent
      sequelae. All but one patient received adjuvant therapy (external and/or
      stereotactic radiotherapy with or without chemotherapy). Follow-up ranged from 15
      to 68 months (mean = 33). Overall survival was 45% (9/20) and local control was
      65% (13/20). CONCLUSIONS: Endoscopic transpterygoid nasopharyngectomy for primary
      and recurrent nasopharyngeal malignancies is feasible and safe in properly
      selected patients. Preliminary outcomes compare to that of conventional
      techniques. Endoscopic resections, however, are demanding; they require
      specialized equipment and a team versed in endoscopic oncologic surgery. Long
      term follow-up and reproducibility remain undefined.

PMID- 21898448
TI  - Patient perceptions of factors leading to spasmodic dysphonia: a combined
      clinical experience of 350 patients.
AB  - PURPOSE: Spasmodic dysphonia (SD) is an idiopathic voice disorder that is
      characterized by either a strained, strangled voice quality or a breathy voice
      with aphonic segments of connected speech. It has been suggested that
      environmental factors play a role in triggering the onset. Clinical observation
      suggests that some patients associate onset with specific events or factors while
      others do not. The purpose of this study was to examine a large database of SD
      patients to determine if specific triggers are associated with the onset of SD.
      PROCEDURES: Retrospective chart review. RESULTS: A total of 350 charts of
      patients with SD were identified and were categorized as either "sudden onset" or
      "gradual onset." One hundred sixty-nine recalled their circumstances surrounding
      onset. Forty-five percent of these patients described the onset as sudden.
      Patient perceptions of inciting events in the sudden onset group were identified
      77% of the time and 2% of the time in the gradual onset group. The most common
      factors identified were stress (42%), upper respiratory infection (33%), and
      pregnancy and parturition (10%). CONCLUSIONS: Thirty-five percent of SD patients
      perceive their disorder to have a sudden onset with identified inciting events.
      This prevalence raises questions regarding possible behavioral and environmental
      factors surrounding the onset of this disorder.

PMID- 21898449
TI  - Thyroid Tubercle of Zuckerkandl: importance in thyroid surgery.
AB  - OBJECTIVE: The Tubercle of Zuckerkandl (TZ), which is the remant of the lateral
      thyroid process, is an important anatomic structure that serves as a reliable
      landmark for the recurrent laryngeal nerve in thyroid surgery. Furthermore,
      removal of the TZ is critical for the adequate performance of a total
      thyroidectomy. However, there is little mention of the TZ in surgical textbooks
      or papers. METHODS: Prospective observational study of 138 consecutive thyroid
      surgeries. The presence of the TZ, its size, and relationship to the recurrent
      laryngeal nerve, were recorded. RESULTS: A total of 211 thyroid lobes were
      included in the study. The TZ was identified in 61.1% of all thyroid lobes. The
      median size was 8 mm (range = 3-40 mm). A TZ was more commonly identified on the
      right (69.6%) than on the left side (53.2%) (P = .02). The recurrent laryngeal
      nerve was found deep to the TZ in 98.4% of cases. CONCLUSIONS: A TZ is present in
      the majority of thyroid lobes. Awareness of the TZ is critical in performing an
      adequate total thyroidectomy, and is very useful as a landmark for the recurrent
      laryngeal nerve.

PMID- 21898450
TI  - Kymographic characterization of vibration in human vocal folds with nodules and
      polyps.
AB  - OBJECTIVES/HYPOTHESIS: Digital kymography (DKG) can provide objective
      quantitative data about vocal fold vibration, which may help distinguish normal
      from pathological vocal folds as well as nodules from polyps. STUDY DESIGN: Case
      control study. METHODS: There were 87 subjects who were separated into three
      groups: control, nodules, and unilateral polyps, and examined using a high-speed
      camera attached to an endoscope. Videos were analyzed using a custom MATLAB
      program, and three DKG line-scan positions (25%, 50%, and 75% of vocal fold
      length) were used in statistical analyses to compare vocal fold vibrational
      frequency, amplitude symmetry index (ASI), amplitude order, and vertical and
      lateral phase difference (VPD and LPD, respectively). RESULTS: Significant
      differences among groups were found in all vibrational parameters except
      frequency. Polyps and nodules groups exhibited greater ASI values (less amplitude
      symmetry) than the control group. Although the control group consistently showed
      its largest amplitudes at the midline, the polyps group showed larger amplitudes
      toward the posterior end of the vocal folds. A significant anterior-posterior
      pattern in amplitude was not found in the nodules group. LPD values were usually
      largest (most symmetrical) in the control group, followed by nodules and polyps.
      LPD at the 25% position allowed for differentiation between polyp and nodule
      groups. The largest VPD (more pronounced mucosal wave) values were usually found
      in the control group. CONCLUSIONS: Vibratory characteristics of normal and
      pathological vocal folds were quantitatively examined and compared using
      multiline DKG. These findings may allow for better characterization of
      pathologies and eventually assist in improving the clinical utility of DKG.

PMID- 21898451
TI  - Physical punishment and childhood aggression: the role of gender and gene
      environment interplay.
AB  - A large body of research has linked spanking with a range of adverse outcomes in
      children, including aggression, psychopathology, and criminal involvement.
      Despite evidence concerning the association of spanking with antisocial behavior,
      not all children who are spanked develop antisocial traits. Given the
      heterogeneous effects of spanking on behavior, it is possible that a third
      variable may condition the influence of corporal punishment on child development.
      We test this possibility using data drawn from a nationally representative
      dataset of twin siblings. Our findings suggest that genetic risk factors
      condition the effects of spanking on antisocial behavior. Moreover, our results
      provide evidence that the interaction between genetic risk factors and corporal
      punishment may be particularly salient for males.

PMID- 21898452
TI  - More than military sexual trauma: interpersonal violence, PTSD, and mental health
      in women veterans.
AB  - Military sexual trauma (MST) is reported by 20-40% of female veterans. The
      purpose of this study of female veterans referred for MST treatment was to
      examine the relationships between lifetime trauma (physical, sexual, and
      psychological) and posttraumatic stress disorder (PTSD), depression, physical
      health, and quality of life using retrospective cross-sectional data from medical
      records. Of the 135 participants, 95.4% reported at least one trauma in addition
      to MST, most notably sexual abuse as adult civilians (77.0%) and as children
      (52.6%). PTSD, depression, and sleep difficulty rates were clinically
      significant. Chronic pain (66.4%) was associated with childhood abuse, physical
      health, sleep difficulties, and coping. Integrating mental and physical health
      treatment is necessary to treat MST and PTSD in female veterans.

PMID- 21898453
TI  - Public house patrons' engagement in hypothetical sexual assault: a test of
      Alcohol Myopia Theory in a field setting.
AB  - Previous research has found that drinking establishments are often antecedent to
      sexual aggression outcomes. In this study, male participants were randomly
      selected from public houses (i.e., "pubs") and asked to imagine themselves in a
      hypothetical intimate encounter in which the female in the scenario stops
      consenting to sexual contact. Participants were given the option to continue
      making sexual advances up to and including sexual intercourse against the woman's
      will. It was hypothesized based on Alcohol Myopia Theory that participant blood
      alcohol concentration (BAC) levels would be associated with hypothetical sexual
      aggression when stereotypical cues of a woman's sexual availability (revealing
      clothing and alcohol use) were present in the scenario. Men's engagement in
      hypothetical sexual aggression was associated with BAC levels, but only when the
      woman was wearing revealing clothing. The sobriety of the female actor was not
      associated with sexual aggression. Results indicate that Alcohol Myopia Theory
      generalizes to a field setting.

PMID- 21898455
TI  - Modified hermeneutic phenomenological approach toward individuals who have
      autism: a response to Newman, Cashin and Waters.

PMID- 21898454
TI  - Patients' experiences of seeking health care for lower urinary tract symptoms.
AB  - A gap between experiencing symptoms and receiving effective treatment persists
      for people with lower urinary tract symptoms (LUTS), even for those who seek
      health care. In order to better understand how patients experience treatment
      seeking for LUTS, we interviewed a racially diverse sample of 90 men and women
      with a range of LUTS about their experiences seeking care. Thematic analysis
      revealed that patients often disclosed urinary symptoms first to primary care
      providers during a general examination or a visit for another health problem.
      Patients seek provider assistance typically when symptoms have intensified or are
      causing worry, and a desire for treatment trumps potential embarrassment; among
      women patients, feeling comfortable with a provider also is important for
      disclosing LUTS.

PMID- 21898456
TI  - Effect of glutaraldehyde fixation on bacterial cells observed by atomic force
      microscopy.
AB  - Atomic force microscopy (AFM) is a promising microscopy technique that can
      provide high-resolution images of bacterial cells without fixation. Three species
      of bacteria, Xanthomonas campestris, Pseudomonas syringae, and Bacillus subtilis,
      were used in this study. AFM images were obtained from unfixed and glutaraldehyde
      fixed cells, and cell height was measured. The mean height of bacterial cells
      prepared by fixation was higher than that of those prepared by nonfixation.
      However, the height changes were different between Gram-negative and Gram
      positive bacteria: the mean height of two fixed Gram-negative bacteria, X.
      campestris and P. syringae, increased by 112.31 and 84.08%, respectively, whereas
      Gram-positive bacterium, B. subtilis, increased only by 38.79%. The results above
      indicated that glutaraldehyde fixation could affect the measured height of cells
      imaged by AFM; further more, the effect of glutaraldehyde fixation on the
      measured height of Gram-negative bacterial cells imaged by AFM seemed much more
      than on that of Gram-positive bacterial cells.

PMID- 21898457
TI  - The study on the atomic force microscopy base nanoscale electrical discharge
      machining.
AB  - This study proposes an innovative atomic force microscopy (AFM) based nanoscale
      electrical discharge machining (AFM-based nanoEDM) system which combines an AFM
      with a self-produced metallic probe and a high-voltage generator to create an
      atmospheric environment AFM-based nanoEDM system and a deionized water (DI water)
      environment AFM-based nanoEDM system. This study combines wire-cut processing and
      electrochemical tip sharpening techniques on a 40-um thick stainless steel sheet
      to produce a high conductive AFM probes, the production can withstand high
      voltage and large current. The tip radius of these probes is approximately 40 nm.
      A probe test was executed on the AFM using probes to obtain nanoscales morphology
      of Si wafer surface. The silicon wafer was as a specimen to carry out AFM-base
      nanoEDM process in atmospheric and DI water environments by AFM-based nanoEDM
      system. After experiments, the results show that the atmospheric and DI water
      environment AFM-based nanoEDM systems operate smoothly. From experimental
      results, it can be found that the electric discharge depth of the silicon wafer
      at atmospheric environments is a mere 14.54 nm. In a DI water environment, the
      depth of electric discharge of the silicon wafer can reach 25.4 nm. This
      indicates that the EDM ability of DI water environment AFM-based nanoEDM system
      is higher than that of atmospheric environment AFM-based nanoEDM system. After
      multiple nanoEDM process, the tips become blunt. After applying electrochemical
      tip sharpening techniques, the tip radius can return to approximately 40 nm.
      Therefore, AFM probes produced in this study can be reused.

PMID- 21898458
TI  - A statistical model of signal-noise in scanning electron microscopy.
AB  - A statistical model describing signal-noise generation and development along the
      signal formation process in a standard scanning electron microscope (SEM) using
      an Everhart-Thornley secondary electron detector is derived. Noise in the
      detector signal is modeled to originate from a cascade of five signal conversion
      stages. Based on the derived model, general conclusions are drawn concerning the
      total signal-to-noise ratio (SNR) at each stage, and the influence of each stage
      on the total SNR of the detector signal. The model is furthermore applied to a
      real-world SEM, and verified by experimental data.

PMID- 21898459
TI  - Holographic otoscope for nanodisplacement measurements of surfaces under dynamic
      excitation.
AB  - We describe a novel holographic otoscope system for measuring nanodisplacements
      of objects subjected to dynamic excitation. Such measurements are necessary to
      quantify the mechanical deformation of surfaces in mechanics, acoustics,
      electronics, biology, and many other fields. In particular, we are interested in
      measuring the sound-induced motion of biological samples, such as an eardrum. Our
      holographic otoscope system consists of laser illumination delivery (IS), optical
      head (OH), and image processing computer (IP) systems. The IS delivers the object
      beam (OB) and the reference beam (RB) to the OH. The backscattered light coming
      from the object illuminated by the OB interferes with the RB at the camera sensor
      plane to be digitally recorded as a hologram. The hologram is processed by the IP
      using the Fresnel numerical reconstruction algorithm, where the focal plane can
      be selected freely. Our holographic otoscope system is currently deployed in a
      clinic, and is packaged in a custom design. It is mounted in a mechatronic
      positioning system to increase its maneuverability degrees to be conveniently
      positioned in front of the object to be measured. We present representative
      results highlighting the versatility of our system to measure deformations of
      complex elastic surfaces in the wavelength scale including a copper foil membrane
      and postmortem tympanic membrane. SCANNING 33: 342-352, 2011. (c) 2011 Wiley
      Periodicals, Inc.

PMID- 21898460
TI  - Comparison of approaches for microscopic imaging of skin lymphatic vessels.
AB  - Assessment of skin lymphatic vessels is of great significance in understanding
      their roles in many pathological conditions. Our aim was to identify the optimal
      approach for investigation of cutaneous lymphatic system. We performed
      comparative studies on skin lymphatic vessels using immunohistochemistry of
      tissue sections, computer graphic reconstruction method together with
      immunohistochemically stained serial sections and whole mount fluorescence in
      human lower limb. Lymphatic vessels were identified with podoplanin antibody. The
      relative merits and drawbacks of each method in evaluation of structure, spatial
      organization, and distribution of cutaneous lymphatic vessels were described.
      Immunohistology of tissue sections enabled the investigation of the structure and
      distribution of the whole cutaneous lymphatic system in two-dimensional slices,
      whereas three-dimensional morphology of only the most superficial lymph capillary
      network immediately under the epidermis could be evaluated with the whole mount
      technique. Meanwhile, only little segmentation of skin lymphatic vessel from five
      immunohistochemically stained serial sections was reconstructed and evaluated due
      to expense and special skills required using computer graphic three-dimensional
      reconstruction. Furthermore, a great number of artifacts and special skills
      required in its processes leaded to less accurate structure of skin lymphatic
      vessels. Our findings demonstrated that the use of either of the proposed
      techniques alone could not allow a comprehensive analysis of the skin lymphatic
      system due to their relative drawbacks. Combination of immunohistology of tissue
      sections and three-dimensional whole-mount preparations appears to be the best
      candidate for comprehensive evaluation of skin lymphatic system.

PMID- 21898461
TI  - Real-time noninvasive optical diagnosis for colorectal cancer using multiphoton
      microscopy.
AB  - In contrast to colonoscopy biopsy, which contains several disadvantages such as
      bleeding, sampling error, crush artifact, and time-consuming pathological
      procedure, multiphoton microscopy (MPM) enables direct noninvasive visualization
      of tissue architecture and cell morphology in live tissues without the
      administration of exogenous contrast agents. We performed a proof-of-principle
      study to evaluate the feasibility of using MPM to make real-time noninvasive
      optical diagnosis of colorectal cancer by investigating 30 fresh, unfixed, and
      unstained full-thickness colorectal specimens. We found that MPM images
      demonstrated irregular tubular structures, reduced stroma, and cellular and
      nuclear pleomorphism in the cancerous tissues. Cancer cells, characterized by
      irregular size and shape, enlarged nuclei, and increased nuclear-cytoplasmic
      ratio, were clearly observed in MPM images, which were comparable to golden
      standard hematoxylin-eosin staining images. Our findings showed that MPM had the
      potential to make real-time noninvasive optical diagnosis of colorectal cancer.
      With miniaturization and integration of colonoscopy, MPM has a promising future
      in real-time noninvasive "optical biopsy" for colorectal cancer.

PMID- 21898462
TI  - Updating a chiral separation strategy for non-acidic drugs with capillary
      electrochromatography applicable for both chlorinated and non-chlorinated
      polysaccharide selectors.
AB  - A generic strategy for the chiral separation of non-acidic pharmaceuticals was
      updated to complete an approach defined earlier. The selected chiral stationary
      phases are all polysaccharide selectors, chlorinated, and non-chlorinated, namely
      Lux((r))  Amylose 2, Chiralcel((r))  OD-RH, Lux((r))  Cellulose 4, and
      Chiralpak((r))  AD-RH. In this study, the screening step of a strategy defined
      earlier was updated and the optimization steps were re-evaluated for the applied
      chiral stationary phases. These screening and optimization conditions were
      studied by analyzing 20 pharmaceuticals at different organic modifier contents,
      temperatures, or applied voltages. The proposed chiral separation strategy was
      then evaluated with a test set of 19 non-acidic drugs. Seventeen compounds
      (89.5%) of the latter set could be resolved of which eight (42%) were baseline
      separated. The strategy thus proved to be applicable on compounds different from
      those used for its development.

PMID- 21898463
TI  - Enantioselective fungal biotransformation of risperidone in liquid culture medium
      by capillary electrophoresis and hollow fiber liquid-phase microextraction.
AB  - Knowing that microbial transformations of compounds play vital roles in the
      preparation of new derivatives with biological activities, risperidone and its
      chiral metabolites were determined by capillary electrophoresis and hollow fiber
      liquid-phase microextraction after a fungal biotransformation study in liquid
      culture medium. The analytes were extracted from 1 mL liquid culture medium into
      1-octanol impregnated in the pores of the hollow fiber, and into an acid acceptor
      solution inside the polypropylene hollow fiber. The electrophoretic separations
      were carried out in 100 mmol/L sodium phosphate buffer pH 3.0 containing 2.0% w/v
      sulfated-alpha-CD and carboxymethyl-beta-CD 0.5% w/v with a constant voltage of 
      10 kV. The method was linear over the concentration range of 100-5000 ng/mL for
      risperidone and 50-5000 ng/mL for each metabolite enantiomer. Within-day and
      between-day assay precisions and accuracies for all the analytes were studied at
      three concentration levels, and the values of relative standard deviation and
      relative error were lower than 15%. The developed method was applied in a pilot
      biotransformation study employing risperidone as the substrate and the
      filamentous fungus Mucor rouxii. This study showed that the filamentous fungus
      was able to metabolize risperidone enantioselectively into its chiral active
      metabolite, (-)-9-hydroxyrisperidone.

PMID- 21898465
TI  - Modeling the interactions between polyoxometalates and their environment.
AB  - To develop a force field suitable both for polyoxometalates (POMs) and organic
      cations, the Merck molecular force field 94x (MMFF94x) has been selected to
      describe the counterions used in POMs synthesis and has been combined with our
      force field optimized for type-II POMs with electrostatic and Van der Waals
      interactions included in the potential. Nontransferability of force fields is
      well-known and, to overcome this limitation, a charge-scaling factor (SF) has
      been introduced and optimized to tune the POMs force field parameters and adapt
      them to MMFF94x. The mixed MMFF94x/POMFF-II force field has been optimized and
      tested on different clusters based on hepta-molybdate. To validate our mixed
      force field comparison of the results obtained after molecular mechanics (MM),
      geometry optimizations with density-functional (DFT) calculations have been
      performed on the smallest system of interest. This has enabled a study of the
      accuracy of different functionals, especially on the description of hydrogen
      bonding, to be made. Results are promising in terms of structural accuracy. MM
      geometry optimization can be used on small POM clusters, competing reasonably
      well with DFT. When quantum approaches increase considerably the computational
      cost because of the size of the system studied, MM can be used, with the small
      reservation that even if the charge SF introduced improves the performance of the
      force field, further optimizations of the nonbonded term and the model used for
      the atomic charges may be necessary in further studies.

PMID- 21898464
TI  - Solvation properties of N-acetyl-beta-glucosamine: molecular dynamics study
      incorporating electrostatic polarization.
AB  - N-Acetyl-beta-glucosamine (NAG) is an important moiety of glycoproteins and is
      involved in many biological functions. However, conformational and dynamical
      properties of NAG molecules in aqueous solution, the most common biological
      environment, remain ambiguous due to limitations of experimental methods.
      Increasing efforts are made to probe structural properties of NAG and NAG
      containing macromolecules, like peptidoglycans and polymeric chitin, at the
      atomic level using molecular dynamics simulations. In this work, we develop a
      polarizable carbohydrate force field for NAG and contrast simulation results of
      various properties using this novel force field and an analogous nonpolarizable
      (fixed charge) model. Aqueous solutions of NAG and its oligomers are
      investigated; we explore conformational properties (rotatable bond geometry),
      electrostatic properties (dipole moment distribution), dynamical properties (self
      diffusion coefficient), hydrogen bonding (water bridge structure and dynamics),
      and free energy of hydration. The fixed-charge carbohydrate force field exhibits
      deviations from the gas phase relative rotation energy of exocyclic hydroxymethyl
      side chain and of chair/boat ring distortion. The polarizable force field
      predicts conformational properties in agreement with corresponding first
      principles results. NAG-water hydrogen bonding pattern is studied through radial
      distribution functions (RDFs) and correlation functions. Intermolecular hydrogen
      bonding between solute and solvent is found to stabilize NAG solution structures
      while intramolecular hydrogen bonds define glycosidic linkage geometry of NAG
      oligomers. The electrostatic component of hydration free energy is highly
      dependent on force field atomic partial charges, influencing a more favorable
      free energy of hydration in the fixed-charge model compared to the polarizable
      model.

PMID- 21898466
TI  - Density functional theory-based electrochemical models for the oxygen reduction
      reaction: comparison of modeling approaches for electric field and solvent
      effects.
AB  - A series of density functional theory (DFT) based electrochemical models are
      applied to systematically examine the effect of solvent, local electric field,
      and electrode potential on oxygen reduction reaction (ORR) kinetics.
      Specifically, the key elementary reaction steps of molecular oxygen dissociation,
      molecular oxygen protonation, and reduction of a hydroxyl adsorbate to water over
      the Pt(111) surface were considered. The local electric field has slight
      influence on reaction energetics at the vacuum interface. Solvent molecules
      stabilize surface adsorbates, assisting oxygen reduction. A collective solvation
      potential coupled effect is identified by including long range solvent-solvent
      interactions in the DFT model. The dominant path of the ORR reaction varies with
      electrode potential and among the modeling approaches considered. The potential
      dependent reaction path determined from the solvated model qualitatively agrees
      with experiment ORR kinetics.

PMID- 21898467
TI  - Site specificity of OH alpha-H abstraction reaction for a beta-hairpin peptide:
      an ab initio study.
AB  - A beta-hairpin peptide (PDB ID 1UAO) was modeled to explore the backbone
      oxidation of a protein by an OH radical to abstract one alpha-H atom with ab
      initio calculation at the B3LYB/6-31G(d) without any constraint. Three glycine
      residues located at three different sites in 1UAO were used to examine the
      possible site specificity of this backbone oxidation. The pre- and post-reactive
      complexes along with their associated transition states were located and verified
      by the intrinsic reaction coordinate method. The reaction profile of these alpha
      H abstraction reactions was constructed. The effects of the aqueous solution were
      estimated by the conductor-like polarizable continuum model (CPCM) model. Rate
      constants were calculated with transition state theory. The reaction rate of the
      OH alpha-H abstraction varies among these three different sites. The differences
      among these three sites were rationalized in terms of the molecular and
      electronic structures of the reactive complexes along the reaction pathway. The
      explicit solvation effect was estimated through the similar abstraction of a
      zwitterionic glycine with the combination of microsolvation and a CPCM model. Our
      results indicate that the alpha-H abstraction at certain sites requires explicit
      salvation to obtain accurate results. A replica exchange molecular dynamics
      simulation was performed to demonstrate the structural change due to this type of
      abstraction.

PMID- 21898468
TI  - Kinetic isotope effects calculated with the instanton method.
AB  - The ring-opening reaction of the cyclopropylcarbinyl radical proceeds via heavy
      atom tunneling at low temperature. We used instanton theory to calculate
      tunneling rates and kinetic isotope effects with on-the-fly calculation of
      energies by density functional theory (B3LYP). The accuracy was verified by
      explicitly correlated coupled-cluster calculations (UCCSD(T)-F12). At cryogenic
      temperatures, we found protium/deuterium KIEs up to 13 and inverse KIEs down to
      0.2. We also studied an intramolecular tautomerization reaction. A simple and
      computationally efficient method is proposed to calculate KIEs with the instanton
      method: the instanton path is assumed to be independent of the atomic masses.
      This results in surprisingly good estimates of the KIEs for the
      cyclopropylcarbinyl radical and for the secondary KIEs of the tautomerization.
      Challenges and capabilities of the instanton method for calculating KIEs are
      discussed.

PMID- 21898469
TI  - The 2010 Malcolm Ferguson-Smith Young Investigator Award.

PMID- 21898470
TI  - Prenatal identification of an accessory lower limb.

PMID- 21898471
TI  - Combined effects of 60 Hz electromagnetic field exposure with various stress
      factors on cellular transformation in NIH3T3 cells.
AB  - Epidemiological studies have suggested that extremely low-frequency magnetic
      fields (ELF-MF) are associated with an increased incidence of cancer. Studies
      using in vitro systems have reported mixed results for the effects of ELF-MF
      alone, and the World Health Organization (WHO) Research Agenda published in 2007
      suggested that high priority research should include an evaluation of the co
      carcinogenic effects of ELF-MF exposure using in vitro models. Here, the
      carcinogenic potential of ELF-MF exposure alone and in combination with various
      stress factors was investigated in NIH3T3 mouse fibroblasts using an in vitro
      cellular transformation assay. NIH3T3 cells were exposed to a 60 Hz ELF-MF (1 mT)
      alone or in combination with ionizing radiation (IR), hydrogen peroxide (H2O2),
      or c-Myc overexpression, and the resulting number of anchorage-independent
      colonies was counted. A 4 h exposure of NIH3T3 cells to ELF-MF alone produced no
      cell transformation. Moreover, ELF exposure did not influence the transformation
      activity of IR, H2O2, or activated c-Myc in our in vitro assay system, suggesting
      that 1 mT ELF-MF did not affect any additive or synergistic transformation
      activities in combination with stress factors such as IR, H2O2, or activated c
      Myc in NIH3T3 cells.

PMID- 21898472
TI  - Incorporation of phylogeny in biological diversity measurement: drawbacks of
      extensively used indices, and advantages of quadratic entropy.

PMID- 21898473
TI  - Salivary peptidome in type 1 diabetes mellitus.
AB  - Diabetic patients show a high susceptibility to oral diseases of inflammatory,
      catabolic and chronic nature with potential impact on saliva composition. In this
      study, our purpose was to characterize type 1 diabetes-induced alterations in the
      salivary peptidome aiming to find prospective biomarkers for type 1 diabetes oral
      health evaluation. Peptidomic analysis of saliva from controls (n = 5) and type 1
      diabetic patients (n = 5) were performed by liquid chromatography followed by
      mass spectrometry. The proteolytic activity and metalloproteinases expression was
      accessed by zymography and slot blot analysis, respectively. Data evidenced a
      significant increase in the percentage of peptides in diabetic patients
      paralleled by a higher proteolytic activity, compared with healthy individuals.
      The nonsalivary gland protein fragments identified in saliva were mainly derived
      from collagen and extracellular matrix proteins, namely collagen type I. The
      cleavage site frequency analysis showed significant differences between healthy
      and type 1 diabetic individuals, highlighting the activity of proteases such as
      matrix metalloproteinase-9 and cathepsin D. Our results highlight salivary
      collagen fragments as potential biomarkers to follow up diabetes-related oral
      damage.

PMID- 21898474
TI  - Determination of therapeutic oligonucleotides using capillary gel
      electrophoresis.
AB  - Oligonucleotides have developed into highly versatile and selective therapeutics
      over the past 20 years. More than five discrete mechanisms of action have been
      reported and more than 10 different chemical modifications have been used to
      extend their in vivo half-life and reduce their toxicity. Capillary gel
      electrophoresis (CGE) has been used extensively for the quantitative analysis of
      oligonucleotide therapeutics in both preclinical and clinical studies since the
      1990s. The success of CGE is based on its extraordinary resolving power, which
      allows for the simultaneous determination of the parent drug and its metabolites.
      More recently, capillary gel electrophoresis has seen renewed interest with the
      emergence of replaceable gels with single-base resolving power and new capillary
      electrophoresis-mass spectrometry interfaces. This review discusses the
      bioanalysis of therapeutic oligonucleotides showing the evolution of the field
      over the past two decades leading to the current new approaches. Included in this
      review are topics such as different gel types, sample introduction modes, sample
      extraction procedures, separation conditions and detection methods used in CGE,
      along with discussions of the successes and limitations associated with each.

PMID- 21898475
TI  - High-performance liquid chromatographic analysis of lacosamide in canine serum
      using ultraviolet detection: application to pre-clinical pharmacokinetics in
      dogs.
AB  - A method for analysis of lacosamide [(R)-2-acetamido-N-benzyl-3
      methoxypropionamide] is needed for both human and veterinary pharmacokinetic
      investigations. While lacosamide is currently used to manage partial-onset
      seizures in humans suffering from epilepsy, it is also presently being
      investigated for use in the treatment of canine epilepsy in veterinary medicine.
      Currently, no dosing regimen for the drug exists in dogs. A novel and simple high
      performance liquid chromatography method was developed for determination of
      lacosamide in dog serum. Serum proteins (0.1 mL) were precipitated with -20.0
      degrees C acetonitrile after addition of the internal standard, daidzein.
      Separation was achieved with a Phenomenex(r) Luna(r) C18 (2) (5 um, 250 * 4.60
      mm) column with ultraviolet detection at 210 nm. The calibration curves were
      linear ranging from 0.5 to 25 ug/mL. Precision of the assay was <13% (RSD) and
      was within 12% for all points in the calibration curve. The limit of quantitation
      for this method was 0.5 ug/mL. The assay was applied successfully to a pre
      clinical study of lacosamide pharmacokinetics in dogs.

PMID- 21898476
TI  - Dendritic cell regulation of carbon tetrachloride-induced murine liver fibrosis
      regression.
AB  - Although hepatic fibrosis typically follows chronic inflammation, fibrosis will
      often regress after cessation of liver injury. In this study, we examined whether
      liver dendritic cells (DCs) play a role in liver fibrosis regression using carbon
      tetrachloride to induce liver injury. We examined DC dynamics during fibrosis
      regression and their capacity to modulate liver fibrosis regression upon
      cessation of injury. We show that conditional DC depletion soon after
      discontinuation of the liver insult leads to delayed fibrosis regression and
      reduced clearance of activated hepatic stellate cells, the key fibrogenic cell in
      the liver. Conversely, DC expansion induced either by Flt3L (fms-like tyrosine
      kinase-3 ligand) or adoptive transfer of purified DCs accelerates liver fibrosis
      regression. DC modulation of fibrosis was partially dependent on matrix
      metalloproteinase (MMP)-9, because MMP-9 inhibition abolished the Flt3L-mediated
      effect and the ability of transferred DCs to accelerate fibrosis regression. In
      contrast, transfer of DCs from MMP-9-deficient mice failed to improve fibrosis
      regression. CONCLUSION: Taken together, these results suggest that DCs increase
      fibrosis regression and that the effect is correlated with their production of
      MMP-9. The results also suggest that Flt3L treatment during fibrosis resolution
      merits evaluation to accelerate regression of advanced liver fibrosis.

PMID- 21898477
TI  - Intensive care of the patient with cirrhosis.
AB  - Acute deterioration of patients with cirrhosis manifests as multiple organ
      failure requiring admission to an intensive care unit. Precipitating events may
      be viral hepatitis, typically in Asia, and drug or alcoholic hepatitis and
      variceal hemorrhage in the West. Patients with cirrhosis in the intensive care
      unit have a high mortality, and each admission is associated with a mean charge
      of US $116,200. Prognosis is determined by the number of organs failing
      (sequential organ failure assessment [SOFA] score), the presence of infection,
      and the degree of liver dysfunction (Child-Turcotte-Pugh or Model for End-Stage
      Liver Disease scores). The most common organ failing is the kidney; sepsis is
      associated with further deterioration in liver function by compromise of the
      microcirculation. Care of these critically ill patients with impending multiple
      organ failure requires a team approach with expertise in both hepatology and
      critical care. Treatment is aimed at preventing further deterioration in liver
      function, reversing precipitating factors, and supporting failing organs. Liver
      transplantation is required in selected patients to improve survival and quality
      of life. Treatment is futile in some patients, but it is difficult to identify
      these patients a priori. Artificial and bioartificial liver support systems have
      thus far not demonstrated significant survival benefit in these patients.

PMID- 21898478
TI  - Association of gene expression involving innate immunity and genetic variation in
      interleukin 28B with antiviral response.
AB  - Innate immunity plays an important role in host antiviral response to hepatitis C
      viral (HCV) infection. Recently, single nucleotide polymorphisms (SNPs) of IL28B
      and host response to peginterferon alpha (PEG-IFNalpha) and ribavirin (RBV) were
      shown to be strongly associated. We aimed to determine the gene expression
      involving innate immunity in IL28B genotypes and elucidate its relation to
      response to antiviral treatment. We genotyped IL28B SNPs (rs8099917 and
      rs12979860) in 88 chronic hepatitis C patients treated with PEG-IFNalpha-2b/RBV
      and quantified expressions of viral sensors (RIG-I, MDA5, and LGP2), adaptor
      molecule (IPS-1), related ubiquitin E3-ligase (RNF125), modulators (ISG15 and
      USP18), and IL28 (IFNlambda). Both IL28B SNPs were 100% identical; 54 patients
      possessed rs8099917 TT/rs12979860 CC (IL28B major patients) and 34 possessed
      rs8099917 TG/rs12979860 CT (IL28B minor patients). Hepatic expressions of viral
      sensors and modulators in IL28B minor patients were significantly up-regulated
      compared with that in IL28B major patients (~ 3.3-fold, P < 0.001). However,
      expression of IPS-1 was significantly lower in IL28B minor patients (1.2-fold, P
      = 0.028). Expressions of viral sensors and modulators were significantly higher
      in nonvirological responders (NVR) than that in others despite stratification by
      IL28B genotype (~ 2.6-fold, P < 0.001). Multivariate and ROC analyses indicated
      that higher RIG-I and ISG15 expressions and RIG-I/IPS-1 expression ratio were
      independent factors for NVR. IPS-1 down-regulation in IL28B minor patients was
      confirmed by western blotting, and the extent of IPS-1 protein cleavage was
      associated with the variable treatment response. CONCLUSION: Gene expression
      involving innate immunity is strongly associated with IL28B genotype and response
      to PEG-IFNalpha/RBV. Both IL28B minor allele and higher RIG-I and ISG15
      expressions and RIG-I/IPS-1 ratio are independent factors for NVR.

PMID- 21898479
TI  - Feasibility and diagnostic performance of the FibroScan XL probe for liver
      stiffness measurement in overweight and obese patients.
AB  - Failure of liver stiffness measurement (LSM) by transient elastography (TE,
      FibroScan) and unreliable results occur in ~ 5% and 15% of patients,
      respectively, mainly due to obesity. In this multicenter study, we evaluated the
      feasibility and performance of the novel FibroScan XL probe in 276 patients with
      chronic liver disease (42% viral hepatitis, 46% nonalcoholic fatty liver disease
      [NAFLD]) and a body mass index (BMI) >= 28 kg/m(2) . Patients underwent liver
      biopsy and TE with the standard M and XL probes. TE failure was defined as no
      valid LSMs and unreliable examinations as <10 valid LSMs or an interquartile
      range (IQR)/LSM >30% or success rate <60%. Probe performance for diagnosing >= F2
      fibrosis and cirrhosis (F4) versus biopsy were examined using areas under
      receiver operating characteristic curves (AUROC). FibroScan failure was less
      frequent with the XL probe than the M probe (1.1% versus 16%) and the XL probe
      was more often reliable (73% versus 50%; both P < 0.00005). Reliable results with
      the XL probe were obtained in 61% of patients in whom the M probe was unreliable.
      Among 178 patients with >= 10 valid LSMs using both probes, liver stiffness was
      highly correlated between probes (rho = 0.86; P < 0.0005); however, median liver
      stiffness was lower using the XL probe (6.8 versus 7.8 kPa; P < 0.00005). The
      AUROC of the XL and M probes were similar for >= F2 fibrosis (0.83 versus 0.86; P
      = 0.19) and cirrhosis (0.94 versus 0.91; P = 0.28). CONCLUSION: Compared with the
      M probe, the FibroScan XL probe reduces TE failure and facilitates reliable LSM
      in obese patients. Although the probes have comparable accuracy, lower liver
      stiffness cutoffs will be necessary when the XL probe is used to noninvasively
      assess liver fibrosis.

PMID- 21898480
TI  - Toll-like receptor 2-mediated innate immune response in human nonparenchymal
      liver cells toward adeno-associated viral vectors.
AB  - Adeno-associated viral vectors (rAAV) are frequently used in gene therapy trials.
      Although rAAV vectors are of low immunogenicity, humoral as well as T cell
      responses may be induced. While the former limits vector reapplication, the
      expansion of cytotoxic T cells correlates with liver inflammation and loss of
      transduced hepatocytes. Because adaptive immune responses are a consequence of
      recognition by the innate immune system, we aimed to characterize cell autonomous
      immune responses elicited by rAAV in primary human hepatocytes and nonparenchymal
      liver cells. Surprisingly, Kupffer cells, but also liver sinusoidal endothelial
      cells, mounted responses to rAAV, whereas neither rAAV2 nor rAAV8 were recognized
      by hepatocytes. Viral capsids were sensed at the cell surface as pathogen
      associated molecular patterns by Toll-like receptor 2. In contrast to the Toll
      like receptor 9-mediated recognition observed in plasmacytoid dendritic cells,
      immune recognition of rAAV in primary human liver cells did not induce a type I
      interferon response, but up-regulated inflammatory cytokines through activation
      of nuclear factor kappaB. CONCLUSION: Using primary human liver cells, we
      identified a novel mechanism of rAAV recognition in the liver, demonstrating that
      alternative means of sensing rAAV particles have evolved. Minimizing this
      recognition will be key to improving rAAV-mediated gene transfer and reducing
      side effects in clinical trials due to immune responses against rAAV.

PMID- 21898481
TI  - Shedding of syndecan-1 from human hepatocytes alters very low density lipoprotein
      clearance.
AB  - We recently showed that the heparan sulfate proteoglycan syndecan-1 mediates
      hepatic clearance of triglyceride-rich lipoproteins in mice based on systemic
      deletion of syndecan-1 and hepatocyte-specific inactivation of sulfotransferases
      involved in heparan sulfate biosynthesis. Here, we show that syndecan-1 expressed
      on primary human hepatocytes and Hep3B human hepatoma cells can mediate binding
      and uptake of very low density lipoprotein (VLDL). Syndecan-1 also undergoes
      spontaneous shedding from primary human and murine hepatocytes and Hep3B cells.
      In human cells, phorbol myristic acid induces syndecan-1 shedding, resulting in
      accumulation of syndecan-1 ectodomains in the medium. Shedding occurs through a
      protein kinase C-dependent activation of ADAM17 (a disintegrin and
      metalloproteinase 17). Phorbol myristic acid stimulation significantly decreases
      DiD (1,1'-dioctadecyl-3,3,3',3'-tetramethylindodicarbocyanine perchlorate)-VLDL
      binding to cells, and shed syndecan-1 ectodomains bind to VLDL. Although mouse
      hepatocytes appear resistant to induced shedding in vitro, injection of
      lipopolysaccharide into mice results in loss of hepatic syndecan-1, accumulation
      of ectodomains in the plasma, impaired VLDL catabolism, and hypertriglyceridemia.
      CONCLUSION: These findings suggest that syndecan-1 mediates hepatic VLDL turnover
      in humans as well as in mice and that shedding might contribute to
      hypertriglyceridemia in patients with sepsis.

PMID- 21898482
TI  - Amiodarone hepatotoxicity.

PMID- 21898483
TI  - Early changes in interferon signaling define natural killer cell response and
      refractoriness to interferon-based therapy of hepatitis C patients.
AB  - Natural killer (NK) cells exhibit a polarized phenotype with increased
      cytotoxicity and decreased interferon gamma (IFN-gamma) production in chronic
      hepatitis C virus (HCV) infection. Here, we asked whether this is caused by type
      I interferon (IFN)-induced expression and phosphorylation levels of signal
      transducer and activator of transcription (STAT) molecules in NK cells and
      whether it affects the response and refractoriness of NK cells to IFN-alpha-based
      therapy of HCV. STAT1 levels in NK cells were significantly higher in patients
      with chronic HCV infection than in uninfected controls. STAT1 levels and
      induction of phosphorylated STAT1 (pSTAT1) increased further during IFN-alpha
      based therapy with preferential STAT1 over STAT4 phosphorylation. Induction of
      pSTAT1 correlated with increased NK cytotoxicity (tumor necrosis factor-apoptosis
      inducing ligand [TRAIL] expression and degranulation) and decreased IFN-gamma
      production. NK cells from patients with a greater than 2 log(10) first-phase HCV
      RNA decline to IFN-alpha-based therapy (>99% IFN effectiveness) displayed strong
      pSTAT1 induction in vivo and were refractory to further stimulation in vitro. In
      contrast, NK cells from patients with a less than 2 log(10) first-phase HCV RNA
      decline exhibited lower pSTAT1 induction in vivo (P = 0.024), but retained
      greater IFN-alpha responsiveness in vitro (P = 0.024). NK cells of all patients
      became refractory to in vivo and in vitro stimulation by IFN-alpha during the
      second-phase virological response. CONCLUSION: These data show that IFN-alpha
      induced modulation of STAT1/4 phosphorylation underlies the polarization of NK
      cells toward increased cytotoxicity and decreased IFN-gamma production in HCV
      infection, and that NK cell responsiveness and refractoriness correlate to the
      antiviral effectiveness of IFN-alpha-based therapy.

PMID- 21898484
TI  - Immunization with aspartate-beta-hydroxylase-loaded dendritic cells produces
      antitumor effects in a rat model of intrahepatic cholangiocarcinoma.
AB  - Dendritic cells (DCs) capture and process proteins and present peptides on the
      cell surface in the context of major histocompatibility complex I and II
      molecules to induce antigen-specific T cell immune responses. The aims of this
      study were to (1) employ an expanded and purified DC population and load them
      with aspartate-beta-hydroxylase (ASPH), a highly expressed tumor-associated cell
      surface protein, and (2) to determine if immunization induced antitumor effects
      in an orthotopic rat model of intrahepatic cholangiocarcinoma. Splenocytes were
      incubated with ASPH-coated beads and passed through a magnetic field to yield an
      80% pure DC OX62+ population. This DC subset was stimulated with granulocyte
      macrophage colony-stimulating factor, interleukin-4, CD40L, and interferon-gamma,
      resulting in a 40-fold increase in interleukin-12A messenger RNA expression to
      subsequently generate a T helper 1-type immune response. After incubation with
      the cytokine cocktail, DCs were found to have matured, as demonstrated by
      increased expression of CD40, CD80, and CD86 costimulatory molecules.
      Immunization with ASPH-loaded DCs induced antigen-specific immunity. A clone of
      the parental tumorigenic rat BDEneu cholangiocyte cell line, designated BDEneu
      CL24, was found to have the highest number of cells expressing this surface
      protein (97%); it maintained the same phenotypic characteristics of the parental
      cell line and was used to produce intrahepatic tumors in immunocompetent
      syngeneic Fisher-344 rats. Immunization with ASPH-loaded DCs generated
      cytotoxicity against cholangiocarcinoma cells in vitro and significantly
      suppressed intrahepatic tumor growth and metastasis, and was associated with
      increased CD3+ lymphocyte infiltration into the tumors. CONCLUSION: These
      findings suggest that immunization with ASPH-loaded DCs may constitute a novel
      therapeutic approach for intrahepatic cholangiocarcinoma, because this protein
      also appears to be highly conserved and expressed on human hepatobiliary tumors.

PMID- 21898485
TI  - Immunoglobulin M levels inversely correlate with CD40 ligand promoter methylation
      in patients with primary biliary cirrhosis.
AB  - The cross-talk of cluster of differentiation (CD)40/CD40 ligand (CD40L) plays a
      key role in CD4(+) T-cell priming, B-cell terminal maturation, and immunoglobulin
      (Ig) class-switch recombination. Genetic defects in the CD40L lead to a disorder
      characterized by elevated concentrations of serum IgM and immunodeficiency.
      Patients with primary biliary cirrhosis (PBC) characteristically show circulating
      antimitochondrial antibodies (AMAs), liver-infiltrating autoreactive T
      lymphocytes against mitochondrial antigens, and high levels of IgM. We
      hypothesized that CD40L may play a key role in the pathogenesis of the elevated
      serum IgM and analyzed genetic and epigenetic modifications of the gene coding
      for CD40L in CD4(+) and CD8(+) T cells isolated from circulating mononuclear
      cells from PBC patients and healthy controls. We herein demonstrate significantly
      lower levels of DNA methylation of the CD40L promoter in CD4(+) T cells from PBC
      patients, as compared with controls, and this decreased methylation was inversely
      correlated with levels of serum IgM in PBC patients. CONCLUSION: The findings of
      an absence of genetic modifications of the CD40L gene, in concert with decreased
      DNA methylation of the CD40L promoter in PBC patients, suggests that
      environmental factors, rather than genetics, must play a major role in the
      pathogenesis of elevated serum IgM in PBC.

PMID- 21898486
TI  - Genetic interactions between hepatocyte nuclear factor-6 and Notch signaling
      regulate mouse intrahepatic bile duct development in vivo.
AB  - Notch signaling and hepatocyte nuclear factor-6 (HNF-6) are two genetic factors
      known to affect lineage commitment in the bipotential hepatoblast progenitor cell
      (BHPC) population. A genetic interaction involving Notch signaling and HNF-6 in
      mice has been inferred through separate experiments showing that both affect BHPC
      specification and bile duct morphogenesis. To define the genetic interaction
      between HNF-6 and Notch signaling in an in vivo mouse model, we examined the
      effects of BHPC-specific loss of HNF-6 alone and within the background of BHPC
      specific loss of recombination signal binding protein immunoglobulin kappa J (RBP
      J), the common DNA-binding partner of all Notch receptors. Isolated loss of HNF-6
      in this mouse model fails to demonstrate a phenotypic variance in bile duct
      development compared to control. However, when HNF-6 loss is combined with RBP-J
      loss, a phenotype consisting of cholestasis, hepatic necrosis, and fibrosis is
      observed that is more severe than the phenotype seen with Notch signaling loss
      alone. This phenotype is associated with significant intrahepatic biliary system
      abnormalities, including an early decrease in biliary epithelial cells, evolving
      to ductular proliferation and a decrease in the density of communicating
      peripheral bile duct branches. In this in vivo model, simultaneous loss of both
      HNF-6 and RBP-J results in down-regulation of both HNF-1beta and Sox9 (sex
      determining region Y-related HMG box transcription factor 9). CONCLUSION: HNF-6
      and Notch signaling interact in vivo to control expression of downstream
      mediators essential to the normal development of the intrahepatic biliary system.
      This study provides a model to investigate genetic interactions of factors
      important to intrahepatic bile duct development and their effect on cholestatic
      liver disease phenotypes.

PMID- 21898487
TI  - End-stage liver disease candidates at the highest model for end-stage liver
      disease scores have higher wait-list mortality than status-1A candidates.
AB  - Candidates with fulminant hepatic failure (Status-1A) receive the highest
      priority for liver transplantation (LT) in the United States. However, no studies
      have compared wait-list mortality risk among end-stage liver disease (ESLD)
      candidates with high Model for End-Stage Liver Disease (MELD) scores to those
      listed as Status-1A. We aimed to determine if there are MELD scores for ESLD
      candidates at which their wait-list mortality risk is higher than that of Status
      1A, and to identify the factors predicting wait-list mortality among those who
      are Status-1A. Data were obtained from the Scientific Registry of Transplant
      Recipients for adult LT candidates (n = 52,459) listed between September 1, 2001,
      and December 31, 2007. Candidates listed for repeat LT as Status-1 A were
      excluded. Starting from the date of wait listing, candidates were followed for 14
      days or until the earliest occurrence of death, transplant, or granting of an
      exception MELD score. ESLD candidates were categorized by MELD score, with a
      separate category for those with calculated MELD > 40. We compared wait-list
      mortality between each MELD category and Status-1A (reference) using time
      dependent Cox regression. ESLD candidates with MELD > 40 had almost twice the
      wait-list mortality risk of Status-1A candidates, with a covariate-adjusted
      hazard ratio of HR = 1.96 (P = 0.004). There was no difference in wait-list
      mortality risk for candidates with MELD 36-40 and Status-1A, whereas candidates
      with MELD < 36 had significantly lower mortality risk than Status-1A candidates.
      MELD score did not significantly predict wait-list mortality among Status-1A
      candidates (P = 0.18). Among Status-1A candidates with acetaminophen toxicity,
      MELD was a significant predictor of wait-list mortality (P < 0.0009).
      Posttransplant survival was similar for Status-1A and ESLD candidates with MELD >
      20 (P = 0.6). CONCLUSION: Candidates with MELD > 40 have significantly higher
      wait-list mortality and similar posttransplant survival as candidates who are
      Status-1A, and therefore, should be assigned higher priority than Status-1A for
      allocation. Because ESLD candidates with MELD 36-40 and Status-1A have similar
      wait-list mortality risk and posttransplant survival, these candidates should be
      assigned similar rather than sequential priority for deceased donor LT.

PMID- 21898488
TI  - Serum ferritin concentration and transferrin saturation before liver
      transplantation predict decreased long-term recipient survival.
AB  - Serum ferritin (SF) concentration is a widely available parameter used to assess
      iron homeostasis. It has been described as a marker to identify high-risk
      patients awaiting liver transplantation (LT) but is also elevated in systemic
      immune-mediated diseases, metabolic syndrome, and in hemodialysis where it is
      associated with an inferior prognosis. This study analyzed whether SF is not only
      a predictor of liver-related mortality prior to LT but also an independent marker
      of survival following LT. In a dual-center, retrospective study, a cohort of 328
      consecutive first-LT patients from Hannover Medical School, Germany (2003-2008,
      follow-up 1260 days), and 82 consecutive LT patients from Regensburg University
      Hospital, Germany (2003-2007, follow-up 1355 days) as validation cohort were
      analyzed. In patients exhibiting SF >=365 MUg/L versus <365 MUg/L prior to LT, 1
      , 3-, and 5-year post-LT survival was 73.3% versus 81.1%, 64.4% versus 77.3%, and
      61.1% versus 74.4%, respectively (overall survival P = 0.0097), which was
      confirmed in the validation cohort (overall survival of 55% versus 83.3%, P =
      0.005). Multivariate analyses identified SF >=365 MUg/L combined with transferrin
      saturation (TFS) <55%, hepatocellular carcinoma, and the survival after LT (SALT)
      score as independent risk factors for death. In patients with SF concentrations
      >=365 MUg/L and TFS <55%, overall survival was 54% versus 74.8% in the remaining
      group (P = 0.003). In the validation cohort, it was 28.6% versus 72% (P = 0.017),
      respectively. CONCLUSION: SF concentration >=365 MUg/L in combination with TFS
      <55% before LT is an independent risk factor for mortality following LT. Lower
      TFS combined with elevated SF concentrations indicate that acute phase mechanisms
      beyond iron overload may play a prognostic role. SF concentration therefore not
      only predicts pre-LT mortality but also death following LT.

PMID- 21898489
TI  - Ribavirin pharmacokinetics and interleukin 28B plus cytochrome P450 27B1 single
      nucleotide polymorphisms as predictors of response to pegylated
      interferon/ribavirin treatment in patients infected with hepatitis C virus
      genotype 1/4.

PMID- 21898490
TI  - Apoptosis: a barrier against cancer no more?

PMID- 21898491
TI  - Tenascin-C: a novel mediator of hepatic ischemia and reperfusion injury.
AB  - Hepatic ischemia/reperfusion (IRI) injury remains a major challenge in clinical
      orthotopic liver transplantation (OLT). Tenascin-C (Tnc) is an extracellular
      matrix protein (ECM) involved in various aspects of immunity and tissue injury.
      Using a Tnc-deficient mouse model, we present data that suggest an active role
      for Tnc in liver IRI. We show that Tnc-deficient mice have a reduction in liver
      damage and a significant improvement in liver regeneration after IRI. The
      inability of Tnc(-/-) mice to express Tnc significantly reduced the levels of
      active caspase-3/transferase-mediated dUTP nick end-labeling (TUNEL) apoptotic
      markers and enhanced the expression of the proliferation cell nuclear antigen
      (PCNA) after liver IRI. The lack of Tnc expression resulted in impaired leukocyte
      recruitment and decreased expressions of interleukin (IL)-1beta, IL-6, and CXCL2
      after liver reperfusion. Tnc-deficient livers were characterized by altered
      expression patterns of vascular adhesion molecules, such as vascular cell
      adhesion molecule-1 and platelet endothelial cell adhesion molecule-1 post-IRI.
      Moreover, matrix metalloproteinase-9 (MMP-9) synthesis, which facilitates
      leukocyte transmigration across vascular barriers in liver IRI, was markedly down
      regulated in the absence of Tnc. We also show that Tnc is capable of inducing MMP
      9 expression in isolated neutrophils through Toll-like receptor 4. Therefore, our
      data suggest that Tnc is a relevant mediator of the pathogenic events underlying
      liver IRI. The data also support the view that studies aimed at further
      understanding how newly synthesized ECM molecules, such as Tnc, participate in
      inflammatory responses are needed to improve therapeutic approaches in liver IRI.

PMID- 21898493
TI  - An update on treatment of genotype 1 chronic hepatitis C virus infection: 2011
      practice guideline by the American Association for the Study of Liver Diseases.

PMID- 21898494
TI  - Where are we in the search for noninvasive nonalcoholic steatohepatitis
      biomarkers?

PMID- 21898495
TI  - Metabolic syndrome is also a risk factor for primary liver cancer in patients
      younger than 65 years of age?

PMID- 21898496
TI  - Field-practice study of sorafenib therapy for hepatocellular carcinoma: a
      prospective multicenter study in Italy.
AB  - A multicenter randomized controlled trial established sorafenib as a standard of
      care for patients with advanced hepatocellular carcinoma (HCC). Because the study
      was prematurely interrupted due to survival benefits in the sorafenib arm, we
      conducted an observational study to adequately assess risks and benefits of this
      regimen in field practice. Starting in 2008, all clinically compensated patients
      with advanced HCC and those with an intermediate HCC who were unfit or failed to
      respond to ablative therapies were consecutively evaluated in six liver centers
      in Italy, for tolerability as well as radiologic and survival response to 800
      mg/d sorafenib therapy. Treatment was down-dosed or interrupted according to drug
      label. Two hundred ninety-six patients (88% Child-Pugh A, 75% Barcelona Clinic
      Liver Cancer [BCLC]-C, and 25% BCLC-B) received sorafenib for 3.8 months (95% CI
      3.3-4.4). Two hundred sixty-nine (91%) patients experienced at least one adverse
      event (AE), whereas 161 (54%) had to reduce dosing. Treatment was interrupted in
      103 (44%) for disease progression, in 95 (40%) for an AE, and in 38 (16%) for
      liver deterioration. The median survival was 10.5 months in the overall cohort,
      8.4 months in BCLC-C versus 20.6 months in BCLC-B patients (P < 0.0001), and 21.6
      months in the 77 patients treated for >70% of the time with a half dose versus
      9.6 months in the 219 patients treated for >70% of the time with a full dose. At
      month 2 of treatment, the overall radiologic response was 8%. Eastern Cooperative
      Oncology Group performance status, macrovascular invasion, extrahepatic spread of
      the tumor, radiologic response at month 2, and sorafenib dosing were independent
      predictors of shortened survival. CONCLUSION: Overall, safety, effectiveness, and
      generalizability of sorafenib therapy in HCC was validated in field practice. The
      effectiveness of half-dosed sorafenib may have implications for tailored therapy.

PMID- 21898497
TI  - Alteration of hepatic nuclear receptor-mediated signaling pathways in hepatitis C
      virus patients with and without a history of alcohol drinking.
AB  - The current study tests a hypothesis that nuclear receptor signaling is altered
      in chronic hepatitis C patients and that the altered pattern is specific to
      alcohol drinking history. The expression of a panel of more than 100 genes
      encoding nuclear receptors, coregulators, and their direct/indirect targets was
      studied in human livers. Gene expression pattern was compared between 15 normal
      donor livers and 23 hepatitis C virus (HCV) genotype 1-positive livers from
      patients without a drinking history (matched for age, sex, and body mass index).
      HCV infection increased the expression of nuclear receptors small heterodimer
      partner and constitutive androstane receptor (CAR) as well as genes involved in
      fatty acid trafficking, bile acid synthesis and uptake, and inflammatory
      response. However, the expression of retinoid X receptor (RXR) alpha, peroxisomal
      proliferator-activated receptor (PPAR) alpha and beta as well as steroid
      regulatory element-binding protein (SREBP)-1c was decreased in HCV-infected
      livers. Gene expression pattern was compared in chronic hepatitis C patients with
      and without a drinking history. Alcohol drinking increased the expression of
      genes involved in fatty acid uptake, trafficking, and oxidation, but decreased
      the expression of genes responsible for gluconeogenesis. These changes were
      consistent with reduced fasting plasma glucose levels and altered expression of
      upstream regulators that include RXRalpha, PPARalpha, and CAR. The messenger RNA
      levels of fibroblast growth factor 21, interleukin-10, and fatty acid synthase,
      which are all regulated by nuclear receptors, showed independent correlation with
      hepatic HCV RNA levels. CONCLUSION: Our findings suggest that those genes and
      pathways that showed altered expression could potentially be therapeutic targets
      for HCV infection and/or alcohol drinking-induced liver injury.

PMID- 21898498
TI  - Activation of liver X receptor increases acetaminophen clearance and prevents its
      toxicity in mice.
AB  - Overdose of acetaminophen (APAP), the active ingredient of Tylenol, is the
      leading cause of drug-induced acute liver failure in the United States. As such,
      it is necessary to develop novel strategies to prevent or manage APAP toxicity.
      In this report, we reveal a novel function of the liver X receptor (LXR) in
      preventing APAP-induced hepatotoxicity. Activation of LXR in transgenic (Tg) mice
      or by an LXR agonist conferred resistance to the hepatotoxicity of APAP, whereas
      the effect of LXR agonist on APAP toxicity was abolished in LXR-deficient mice.
      The increased APAP resistance in LXR Tg mice was associated with increased APAP
      clearance, increased APAP sulfation, and decreased formation of toxic APAP
      metabolites. The hepatoprotective effect of LXR may have resulted from the
      induction of antitoxic phase II conjugating enzymes, such as Gst and Sult2a1, as
      well as the suppression of protoxic phase I P450 enzymes, such as Cyp3a11 and
      Cyp2e1. Promoter analysis suggested the mouse Gst isoforms as novel
      transcriptional targets of LXR. The suppression of Cyp3a11 may be accounted for
      by the inhibitory effect of LXR on the PXR-responsive transactivation of Cyp3a11.
      The protective effect of LXR in preventing APAP toxicity is opposite to the
      sensitizing effect of pregnane X receptor, constitutive androstane receptor, and
      retinoid X receptor alpha. CONCLUSION: We conclude that LXR represents a
      potential therapeutic target for the prevention and treatment of Tylenol
      toxicity.

PMID- 21898499
TI  - Recombinant adenovirus carrying the hepatocyte nuclear factor-1alpha gene
      inhibits hepatocellular carcinoma xenograft growth in mice.
AB  - Hepatocyte nuclear factor-1alpha (HNF1alpha) is one of the key transcription
      factors of the HNF family, which plays a critical role in hepatocyte
      differentiation. Substantial evidence has suggested that down-regulation of
      HNF1alpha may contribute to the development of hepatocellular carcinoma (HCC).
      Herein, human cancer cells and tumor-associated fibroblasts (TAFs) were isolated
      from human HCC tissues, respectively. A recombinant adenovirus carrying the
      HNF1alpha gene (AdHNF1alpha) was constructed to determine its effect on HCC in
      vitro and in vivo. Our results demonstrated that HCC cells and HCC tissues
      revealed reduced expression of HNF1alpha. Forced reexpression of HNF1alpha
      significantly suppressed the proliferation of HCC cells and TAFs and inhibited
      the clonogenic growth of hepatoma cells in vitro. In parallel, HNF1alpha
      overexpression reestablished the expression of certain liver-specific genes and
      microRNA 192 and 194 levels, with a resultant increase in p21 levels and
      induction of G(2)/M arrest. Additionally, AdHNF1alpha inhibited the expression of
      cluster of differentiation 133 and epithelial cell adhesion molecule and the
      signal pathways of the mammalian target of rapamycin and transforming growth
      factor beta/Smads. Furthermore, HNF1alpha abolished the tumorigenicity of
      hepatoma cells in vivo. Most interestingly, intratumoral injection of AdHNF1alpha
      significantly inhibited the growth of subcutaneous HCC xenografts in nude mice.
      Systemic delivery of AdHNF1alpha could eradicate the orthotopic liver HCC nodules
      in nonobese diabetic/severe combined immunodeficiency mice. CONCLUSION: These
      results suggest that the potent inhibitive effect of HNF1alpha on HCC is attained
      by inducing the differentiation of hepatoma cells into mature hepatocytes and
      G(2)/M arrest. HNF1alpha might represent a novel, promising therapeutic agent for
      human HCC treatment. Our findings also encourage the evaluation of
      differentiation therapy for tumors of organs other than liver using their
      corresponding differentiation-determining transcription factor.

PMID- 21898500
TI  - Commentary on emergence of hepatitis B virus S gene mutants in patients
      experiencing HBsAg seroconversion after peginterferon therapy.

PMID- 21898501
TI  - Human immunodeficiency virus and liver disease forum 2010: conference
      proceedings.
AB  - Liver disease continues to represent a critical mediator of morbidity and
      mortality in those with human immunodeficiency virus (HIV) infection. The
      frequent presence and overlap of concomitant injurious processes, including
      hepatitis C virus and hepatitis B virus infections, hepatoxicity associated with
      antiretroviral therapeutic agents, alcohol, and other toxins, in the setting of
      immunosuppression lead to rapid fibrotic progression and early development of end
      stage liver disease. This conference summary describes the proceedings of a state
      of-the-art gathering of international experts designed to highlight the status of
      current research in epidemiology, natural history, pathogenesis, and treatment of
      HIV and liver disease.

PMID- 21898502
TI  - Regression of established hepatocellular carcinoma is induced by
      chemoimmunotherapy in an orthotopic murine model.
AB  - The high rate of mortality and frequent incidence of recurrence associated with
      hepatocellular carcinoma (HCC) reveal the need for new therapeutic approaches. In
      this study we evaluated the efficacy of a novel chemoimmunotherapeutic strategy
      to control HCC and investigated the underlying mechanism that increased the
      antitumor immune response. We developed a novel orthotopic mouse model of HCC
      through seeding of tumorigenic hepatocytes from SV40 T antigen (Tag) transgenic
      MTD2 mice into the livers of syngeneic C57BL/6 mice. These MTD2-derived
      hepatocytes form Tag-expressing HCC tumors specifically within the liver. This
      approach provides a platform to test therapeutic strategies and antigen-specific
      immune-directed therapy in an immunocompetent murine model. Using this model we
      tested the efficacy of a combination of oral sunitinib, a small molecule
      multitargeted receptor tyrosine kinase (RTK) inhibitor, and adoptive transfer of
      tumor antigen-specific CD8(+) T cells to eliminate HCC. Sunitinib treatment alone
      promoted a transient reduction in tumor size. Sunitinib treatment combined with
      adoptive transfer of tumor antigen-specific CD8(+) T cells led to elimination of
      established tumors without recurrence. In vitro studies revealed that HCC growth
      was inhibited through suppression of STAT3 signaling. In addition, sunitinib
      treatment of tumor-bearing mice was associated with suppression of STAT3 and a
      block in T-cell tolerance. CONCLUSION: These findings indicate that sunitinib
      inhibits HCC tumor growth directly through the STAT3 pathway and prevents tumor
      antigen-specific CD8(+) T-cell tolerance, thus defining a synergistic
      chemoimmunotherapeutic approach for HCC.

PMID- 21898503
TI  - Transforming growth factor-beta signaling promotes hepatocarcinogenesis induced
      by p53 loss.
AB  - Hepatocellular carcinoma (HCC) results from the accumulation of deregulated tumor
      suppressor genes and/or oncogenes in hepatocytes. Inactivation of TP53 and
      inhibition of transforming growth factor-beta (TGF-beta) signaling are among the
      most common molecular events in human liver cancers. Thus, we assessed whether
      inactivation of TGF-beta signaling, by deletion of the TGF-beta receptor, type II
      (Tgfbr2), cooperates with Trp53 loss to drive HCC formation. Albumin-cre
      transgenic mice were crossed with floxed Trp53 and/or floxed Tgfbr2 mice to
      generate mice lacking p53 and/or Tgfbr2 in the liver. Deletion of Trp53 alone
      (Trp53(KO) ) resulted in liver tumors in approximately 41% of mice by 10 months
      of age, whereas inactivation of Tgfbr2 alone (Tgfbr2(KO) ) did not induce liver
      tumors. Surprisingly, deletion of Tgfbr2 in the setting of p53 loss (Trp53(KO)
      ;Tgfbr2(KO) ) decreased the frequency of mice with liver tumors to around 17% and
      delayed the age of tumor onset. Interestingly, Trp53(KO) and Trp53(KO)
      ;Tgfbr2(KO) mice develop both HCC and cholangiocarcinomas, suggesting that loss
      of p53, independent of TGF-beta, may affect liver tumor formation through effects
      on a common liver stem cell population. Assessment of potential mechanisms
      through which TGF-beta signaling may promote liver tumor formation in the setting
      of p53 loss revealed a subset of Trp53(KO) tumors that express increased levels
      of alpha-fetoprotein. Furthermore, tumors from Trp53(KO) mice express increased
      TGF-beta1 levels compared with tumors from Trp53(KO) ;Tgfbr2(KO) mice. Increased
      phosphorylated Smad3 and ERK1/2 expression was also detected in the tumors from
      Trp53(KO) mice and correlated with increased expression of the TGF-beta
      responsive genes, Pai1 and Ctgf. CONCLUSION: TGF-beta signaling paradoxically
      promotes the formation of liver tumors that arise in the setting of p53
      inactivation.

PMID- 21898505
TI  - Glucocorticoids increase interleukin-6-dependent gene induction by interfering
      with the expression of the suppressor of cytokine signaling 3 feedback inhibitor.
AB  - Glucocorticoids are known to be potent regulators of inflammation and have been
      used pharmacologically against inflammatory, immune, and lymphoproliferative
      diseases for more than 50 years. Due to their possible and well-documented side
      effects, it is crucial to understand the molecular mechanisms and targets of
      glucocorticoid action in detail. Several modes of action have been discussed;
      nevertheless, none of them fully explain all the functions of glucocorticoids.
      Therefore, we analyzed the cross-talk between glucocorticoids and interleukin-6
      (IL-6) in the liver. IL-6 exerts pro-inflammatory as well as anti-inflammatory
      properties and is a main inducer of the acute-phase response. The balance between
      the proinflammatory and anti-inflammatory activities of IL-6 is tightly regulated
      by suppressor of cytokine signaling 3 (SOCS3), a well-known feedback inhibitor of
      IL-6 signaling. Here, it is demonstrated that glucocorticoids enhance IL-6
      dependent gamma-fibrinogen expression. Studying of the underlying mechanism
      revealed prolonged activation of signal transducer and activator of transcription
      3 (STAT3) caused by down-regulation of SOCS3 protein expression. Consequently, in
      SOCS3-deficient cells glucocorticoids do not affect IL-6-induced signal
      transduction. Moreover, in hepatocytes lacking the SOCS3 recruiting motif within
      gp130, IL-6-dependent gamma-fibrinogen expression is not influenced by
      glucocorticoid treatment. CONCLUSION: Glucocorticoids interfere with IL-6-induced
      expression of the feedback inhibitor SOCS3, thereby leading to enhanced
      expression of acute-phase genes in hepatocytes. This mechanism contributes to the
      explanation of how glucocorticoids affect inflammation and acute-phase gene
      induction.

PMID- 21898504
TI  - Comparison of eight diagnostic algorithms for liver fibrosis in hepatitis C: new
      algorithms are more precise and entirely noninvasive.
AB  - The sequential algorithm for fibrosis evaluation (SAFE) and the Bordeaux
      algorithm (BA), which cross-check FibroTest with the aspartate aminotransferase
      to-platelet ratio index (APRI) or FibroScan, are very accurate but provide only a
      binary diagnosis of significant fibrosis (SAFE or BA for Metavir F >= 2) or
      cirrhosis (SAFE or BA for F4). Therefore, in clinical practice, physicians have
      to apply the algorithm for F >= 2, and then, when needed, the algorithm for F4
      ("successive algorithms"). We aimed to evaluate successive SAFE, successive BA,
      and a new, noninvasive, detailed classification of fibrosis. The study included
      1785 patients with chronic hepatitis C, liver biopsy, blood fibrosis tests, and
      FibroScan (the latter in 729 patients). The most accurate synchronous combination
      of FibroScan with a blood test (FibroMeter) provided a new detailed (six classes)
      classification (FM+FS). Successive SAFE had a significantly (P < 10(-3) ) lower
      diagnostic accuracy (87.3%) than individual SAFE for F >= 2 (94.6%) or SAFE for
      F4 (89.5%), and required significantly more biopsies (70.8% versus 64.0% or 6.4%,
      respectively, P < 10(-3) ). Similarly, successive BA had significantly (P <= 10(
      3) ) lower diagnostic accuracy (84.7%) than individual BA for F >= 2 (88.3%) or
      BA for F4 (94.2%), and required significantly more biopsies (49.8% versus 34.6%
      or 24.6%, respectively, P < 10(-3) ). The diagnostic accuracy of the FM+FS
      classification (86.7%) was not significantly different from those of successive
      SAFE or BA. However, this new classification required no biopsy. CONCLUSION: SAFE
      and BA for significant fibrosis or cirrhosis are very accurate. However, their
      successive use induces a significant decrease in diagnostic accuracy and a
      significant increase in required liver biopsy. A new fibrosis classification that
      synchronously combines two fibrosis tests was as accurate as successive SAFE or
      BA, while providing an entirely noninvasive (0% liver biopsy) and more precise
      (six versus two or three fibrosis classes) fibrosis diagnosis.

PMID- 21898506
TI  - Cost-effectiveness of hepatitis C virus antiviral treatment for injection drug
      user populations.
AB  - Injecting drug use is the main risk of hepatitis C virus (HCV) transmission in
      most developed countries. HCV antiviral treatment (peginterferon-alpha +
      ribavirin) has been shown to be cost-effective for patients with no reinfection
      risk. We examined the cost-effectiveness of providing antiviral treatment for
      injecting drug users (IDUs) as compared with treating ex/non-IDUs or no
      treatment. A dynamic model of HCV transmission and disease progression was
      developed, incorporating: a fixed number of antiviral treatments allocated at the
      mild HCV stage over 10 years, no retreatment after treatment failure, potential
      reinfection, and three baseline IDU HCV chronic prevalence scenarios (20%, 40%,
      and 60%). We performed a probabilistic cost-utility analysis estimating long-term
      costs and outcomes measured in quality adjusted life years (QALYs) and
      calculating the incremental cost-effectiveness ratio (ICER) comparing treating
      IDUs, ex/non-IDUs, or no treatment. Antiviral treatment for IDUs is the most cost
      effective option in the 20% and 40% baseline chronic prevalence settings, with
      ICERs compared with no treatment of L 521 and L 2,539 per QALY saved,
      respectively. Treatment of ex/non-IDUs is dominated in these scenarios. At 60%
      baseline prevalence, treating ex/non-IDUs is slightly more likely to be the more
      cost-effective option (with an ICER compared with no treatment of L 6,803), and
      treating IDUs dominated due to high reinfection. A sensitivity analysis indicates
      these rankings hold even when IDU sustained viral response rates as compared with
      ex/non-IDUs are halved. CONCLUSION: Despite the possibility of reinfection, the
      model suggests providing antiviral treatment to IDUs is the most cost-effective
      policy option in chronic prevalence scenarios less than 60%. Further research on
      how HCV treatment for injectors can be scaled up and its impact on prevalence is
      warranted.

PMID- 21898507
TI  - Persistent elevation of hepatocyte growth factor activator inhibitors in
      cholangiopathies affects liver fibrosis and differentiation.
AB  - Alteration of cell surface proteolysis has been proposed to play a role in liver
      fibrosis, a grave complication of biliary atresia (BA). In this study we
      investigated the roles of hepatocyte growth factor activator inhibitor (HAI)-1
      and -2 in the progression of BA. The expression levels of HAI-1 and -2 were
      significantly increased in BA livers compared with those in neonatal hepatitis
      and correlated with disease progression. In BA livers, HAI-1 and -2 were
      coexpressed in cells involved in ductular reactions. In other selective
      cholangiopathies, ductular cells positive for HAI-1 or HAI-2 also increased in
      number. Inflammatory cytokines, growth factors, and bile acids differentially up
      regulated expression of HAI-1 and -2 transcripts in fetal liver cells and this
      induction could be antagonized by a cyclooxygenase-2 inhibitor. Conditioned media
      from cell lines stably overexpressing HAI-1 or HAI-2 enhanced the fibrogenic
      activity of portal fibroblasts and stellate cells, suggesting that both proteins
      might be involved in liver fibrosis. Because HAI-1 and -2 colocalized in ductular
      reactions sharing similar features to those observed during normal liver
      development, we sought to investigate the role of HAI-1 and -2 in
      cholangiopathies by exploring their functions in fetal liver cells. Knockdown of
      HAI-1 or HAI-2 promoted bidirectional differentiation of hepatoblast-derived
      cells. In addition, we showed that the hepatocyte growth factor activator,
      mitogen-activated protein kinase kinase 1, and phosphatidylinositol 3-kinase
      signaling pathways were involved in hepatic differentiation enhanced by HAI-2
      knockdown. CONCLUSION: HAI-1 and -2 are overexpressed in the liver in
      cholangiopathies with ductular reactions and are possibly involved in liver
      fibrosis and hepatic differentiation; they could be investigated as disease
      markers and potential therapeutic targets.

PMID- 21898508
TI  - Genetic variant in PNPLA3 is associated with nonalcoholic fatty liver disease in
      China.

PMID- 21898509
TI  - Drug therapy: telaprevir.

PMID- 21898510
TI  - White monkey syndrome and presumptive copper deficiency in wild savannah baboons.
AB  - In immature wild savannah baboons (Papio cynocephalus), we observed symptoms
      consistent with copper (Cu) deficiency and, more specifically, with a disorder
      referred to as white monkey syndrome (WMS) in laboratory primates. The objectives
      of this study were to characterize this pathology, and test three hypotheses that
      (1) Cu deficiency may have been induced by zinc (Zn) toxicity, (2) it may have
      been induced by molybdenum (Mo) toxicity, and (3) cumulative rainfall during the
      perinatal period and particularly during gestation is an ecological factor
      distinguishing infants afflicted with WMS from non-WMS infants. During 2001-2009,
      we observed 22 instances of WMS out of a total 377 live births in the study
      population. Visible symptoms exhibited by WMS infants included whitening of the
      animal's fur and/or impaired mobility characterized by an apparent "stiffening"
      of the hindlimbs. Occurrence of WMS did not vary significantly by gender.
      However, among individuals that survived at least 180 days, WMS males had a
      significantly lower survivorship probability than non-WMS males. Zn/Cu ratios
      assessed from hair samples of adult female baboons were higher in females who had
      produced at least one WMS offspring relative to females who had not had a WMS
      offspring. This was true even when the hair sample was collected long after the
      birth of the female's afflicted infant. We consider this potentially indicative
      of a robust tendency for low Cu levels induced by elevated Zn intake in some
      individuals. No significant differences of Mo/Cu ratios were observed. Cumulative
      rainfall during gestation (~179 days) was 50% lower for WMS infants relative to
      non-WMS infants. In contrast, rainfall for the two classes of infants did not
      differ in the 180 days before conception or in the 180 days following birth. This
      finding highlights the importance of prenatal ecological conditions in healthy
      fetal development with regard to WMS.

PMID- 21898511
TI  - Aggression in pigtailed macaque (Macaca nemestrina) breeding groups affects
      pregnancy outcome.
AB  - Past research has shown that aggressive behaviors can affect female reproductive
      outcome in nonhuman primate captive breeding programs. In this study, aggressive
      behaviors were recorded in a colony of pigtailed macaque monkeys (Macaca
      nemestrina) and related to pregnancy outcome. For 22 weeks, behavioral data were
      collected from nine breeding groups, consisting of zero to one male (some males
      were removed after a cycle of conceptions for husbandry reasons) and four to
      eight females. Observations included all occurrences of 11 aggressive behaviors
      during 15 min observation sessions, 1-3 times a week. Mean weekly aggression
      levels during the study period were determined for each group as well as for each
      pregnancy. Aggression data were summarized with Principal Components Analyses.
      Results indicate that pigtailed macaque aggression falls into five distinctive
      categories: warn, engage, threaten, pursue, and attack. Breeding groups differed
      in their levels of aggression, even after controlling for group size, presence of
      a sire, and group stability. Levels of the five aggression categories were found
      to affect the probability that a pregnancy ended in either a natural birth of a
      live infant, a clinical intervention producing a live infant, or a nonviable
      outcome. The predictive value of aggression was significant when clinical
      interventions were included as possible reproductive outcomes. Behavioral
      observation of captive groups could identify "risk" conditions affecting
      pregnancy outcome and the requirement for clinical intervention.

PMID- 21898512
TI  - Influence of climatic variables, forest type, and condition on activity patterns
      of Geoffroyi's spider monkeys throughout Mesoamerica.
AB  - Understanding how species cope with variations in climatic conditions, forest
      types and habitat amount is a fundamental challenge for ecologists and
      conservation biologists. We used data from 18 communities of Mesoamerican spider
      monkeys (Ateles geoffroyi) throughout their range to determine whether their
      activity patterns are affected by climatic variables (temperature and rainfall),
      forest types (seasonal and nonseasonal forests), and forest condition (continuous
      and fragmented). Data were derived from 15 published and unpublished studies
      carried out in four countries (Mexico, El Salvador, Costa Rica, and Panama),
      cumulatively representing more than 18 years (221 months, >3,645 hr) of
      behavioral observations. Overall, A. geoffroyi spent most of their time feeding
      (38.4 +/- 14.0%, mean +/- SD) and resting (36.6 +/- 12.8%) and less time
      traveling (19.8 +/- 11.3%). Resting and feeding were mainly affected by rainfall:
      resting time increased with decreasing rainfall, whereas feeding time increased
      with rainfall. Traveling time was negatively related to both rainfall and maximum
      temperature. In addition, both resting and traveling time were higher in seasonal
      forests (tropical dry forest and tropical moist forest) than in nonseasonal
      forests (tropical wet forest), but feeding time followed the opposite pattern.
      Furthermore, spider monkeys spent more time feeding and less time resting (i.e.,
      higher feeding effort) in forest fragments than in continuous forest. These
      findings suggest that global climate changes and habitat deforestation and
      fragmentation in Mesoamerica will threaten the survival of spider monkeys and
      reduce the distributional range of the species in the coming decades.

PMID- 21898513
TI  - Seasonal versatility in the feeding ecology of a group of titis (Callicebus
      coimbrai) in the northern Brazilian Atlantic Forest.
AB  - The feeding behavior of a group of titis (Callicebus coimbrai) was monitored over
      an annual cycle at a site in northeastern Brazil. Behavioral data were collected
      in scan samples (1-min scan at 5-min intervals), and complementary data on fruit
      availability and new leaf cover were collected. Feeding time accounted for 28.9%
      of daily activity. Fruit was the principal item of the diet (61.2% of records)
      and the primary category in all months except September, when it was surpassed by
      leaves. Young leaves were the second most important category (20.0%). The
      consumption of seeds and insects was prominent in November and December. Fifty
      two plant species were exploited, and the Elaeocarpaceae, Myrtaceae, Sapotaceae,
      and Passifloraceae provided the vast majority (86.0%) of plant feeding records.
      The phenological record did not provide a good measure of fruit availability, but
      a strong correlation (r(s) =0.902, P<0.0001, n=12) was found between the
      consumption of leaves and the exploitation of lianas each month. Lianas accounted
      for 28.2% of plant feeding records, and predominated between August and December.
      This suggests that lianas may represent a key factor in the ability of the
      species to tolerate the intense habitat fragmentation found throughout its
      geographic range.

PMID- 21898514
TI  - Sex ratio affects sex-specific innovation and learning in captive ruffed lemurs
      (Varecia variegata and Varecia rubra).
AB  - Recent years have witnessed extensive research into problem solving and
      innovation in primates, yet lemurs have not been subjected to the same level of
      attention as apes and monkeys, and the social context in which novel behavior
      appears has rarely been considered. We gave novel foraging puzzlebox devices to
      seven groups of ruffed lemurs (Varecia variegata and Varecia rubra) to examine
      the factors affecting rates of innovation and social learning. We found, across a
      range of group sex ratios, that animals of the less-represented sex were more
      likely to contact and solve the puzzlebox sooner than those of the more
      represented sex. We established that while some individuals were able to solve
      the puzzleboxes there was no evidence of social learning. Our findings are
      consistent with previously reported male deference as a sexual strategy, but we
      conclude that the need for male deference diminishes when, within a group, males
      are rare.

PMID- 21898515
TI  - Protozoan parasites in group-living primates: testing the biological island
      hypothesis.
AB  - A series of articles by W.J. Freeland published in the 1970s proposed that social
      organization and behavioral processes were heavily influenced by parasitic
      infections, which led to a number of intriguing hypotheses concerning how natural
      selection might act on social factors because of the benefits of avoiding
      parasite infections. For example, Freeland [1979] showed that all individuals
      within a given group harbored identical gastrointestinal protozoan faunas, which
      led him to postulate that social groups were akin to "biological islands" and
      suggest how this isolation could select specific types of ranging and dispersal
      patterns. Here, we reexamine the biological island hypothesis by quantifying the
      protozoan faunas of the same primate species examined by Freeland in the same
      location; our results do not support this hypothesis. In contrast, we quantified
      two general changes in protozoan parasite community of primates in the study area
      of Kibale National Park, Uganda, over the nearly 35 years between sample
      collections: (1) the colobines found free of parasites in the early 1970s are now
      infected with numerous intestinal protozoan parasites and (2) groups are no
      longer biological islands in terms of their protozoan parasites. Whatever the
      ultimate explanation for these changes, our findings have implications for
      studies proposing selective forces shaping primate behavior and social
      organization.

PMID- 21898516
TI  - Sleeping site selection and presleep behavior in wild pigtailed macaques.
AB  - Several factors are likely to control sleeping site selection and presleep
      behavior in nonhuman primates, including predation risk and location of food
      resources. We examined the effects of these factors on the sleeping behavior of
      northern pigtailed macaques (Macaca leonina). While following a troop living in
      the surroundings of the Visitor Center of Khao Yai National Park (Thailand), we
      recorded the physical characteristics and location of each sleeping site, tree,
      the individuals' place in the tree, posture, and behavior. We collected data for
      154 nights between April 2009 and November 2010. The monkeys preferred tall
      sleeping trees (20.9 +/- SD 4.9 m) and high sleeping places (15.8 +/- SD 4.3 m),
      which may be an antipredator strategy. The choice of sleeping trees close to the
      last (146.7 +/- SD 167.9 m) or to the first (150.4 +/- SD 113.0 m) feeding tree
      of the day may save energy and decrease predation risk when monkeys are searching
      for food. Similarly, the choice of sleeping sites close to human settlements
      eases the access to human food during periods of fruit scarcity. Finally, the
      temporal pattern of use of sleeping sites, with a preference for four of the
      sleeping sites but few reuses during consecutive nights, may be a trade-off
      between the need to have several sleeping sites (decreasing detection by
      predators and travel costs to feeding sites), and the need to sleep in well-known
      sites (guaranteeing a faster escape in case of predator attack).

PMID- 21898517
TI  - The response of the frugivorous lion-tailed macaque (Macaca silenus) to a period
      of fruit scarcity.
AB  - Tropical rainforests show seasonal fluctuations in the abundance of fruits
      resulting in periods of resource scarcity for frugivores. We examined the
      response of an obligate frugivore, the lion-tailed macaque (LTM) (Macaca
      silenus), to a period of fruit scarcity in a rainforest in the Western Ghats,
      India. We estimated the abundance and distribution of fruit resources from food
      tree densities obtained from 348 point centered quadrats, and fruit availability
      from phenological monitoring of 195 trees of 15 reported major food species.
      Macronutrient content was estimated for fruits of 15 major food species. We
      estimated time spent feeding on different food items from 1,853 individual scans
      spanning 120 hr of observation of one habituated study group. There was a
      distinct period of fruit scarcity during the drier months of February to mid
      March (Period 1) compared with late March and April (Period 2), separated by
      summer showers. Fruits available in Period 1 had lower soluble carbohydrate and
      lipid content and overall caloric value compared with Period 2. During the lean
      period, the LTM fed more on fruits of Drypetes wightii, which had the highest
      carbohydrate content, than on nectar of Palaquium ellipticum or Ficus spp., which
      had low carbohydrate content. During this period, the resource availability in a
      location significantly influenced the occurrence of feeding there. In Period 2,
      the group fed most on the seeds of Cullenia exarillata, the most abundant tree in
      the home-range and with the highest content of soluble carbohydrates. During this
      period, the abundance of food trees in fruit in a location did not seem to
      influence the occurrence of feeding. Low abundance, stochastic fruiting and, low
      quality might make Ficus spp. a poor fallback option for the LTM.

PMID- 21898518
TI  - Male dispersal in a provisioned multilevel group of Rhinopithecus roxellana in
      Shennongjia Nature Reserve, China.
AB  - Most Old World monkeys show male-biased dispersal. We present the first
      systematic data on male dispersal in a provisioned multilevel group of
      Rhinopithecus roxellana, based on 4.5 years of field observations in Shennongjia
      National Nature Reserve, China. We evaluated both ultimate (inbreeding avoidance
      and male mating competition) and proximate (food availability and predation risk)
      factors influencing male dispersal. The focal group contained 34-53 individuals,
      in 3-4 one-male units (OMUs) and 1 all-male unit (AMU). We observed 37 dispersal
      events involving 10 of 11 adults, 7 of 8 subadults, and 7 of 15 juveniles. Most
      interunit transfers within the focal group occurred around the months of mating
      season. Adult males competed for the leader positions of OMUs mainly through
      aggressive takeovers, and young males transferred from the OMUs to the AMU at the
      median age of 41 months, forced out by leader males. No young males older than 4
      years remained in natal or non-natal OMUs. The male mating competition hypothesis
      was supported. The young males emigrated voluntarily from the focal group at the
      average age of 58.6 months, and no young emigrating male was observed to return,
      suggesting inbreeding avoidance also played a role in the dispersal of young
      males. Most emigration/immigration events were parallel dispersal and occurred
      during intergroup encounters, suggesting increased predation risk during the
      dispersal period. Males were more likely to emigrate/immigrate during the months
      when preferred foods were most available. We compared the dispersal patterns in
      R. roxellana with those in gelada baboons and hamadryas baboons, both living in
      multilevel societies. Similar to R. roxellana, young male geladas disperse at
      puberty, but they may return and breed in their natal groups. Males in hamadryas
      also disperse, but much less commonly than in R. roxellana. Provisioning may have
      influenced results, and confirming studies on unprovisioned groups would be
      valuable.

PMID- 21898519
TI  - Respiratory functions in adolescents hospitalized for anorexia nervosa: a
      prospective study.
AB  - OBJECTIVE: To examine the effects of malnourishment on the respiratory system of
      adolescents with anorexia nervosa (AN) hospitalized for medical stabilization.
      METHOD: Prospective study. STUDY GROUP: hospitalized adolescents with recent
      onset (<1 year) AN. CONTROL GROUP: adolescents hospitalized for other diagnoses.
      Excluded: participants with lung disease. RESULTS: Patients' characteristics
      (mean +/- SD) for the AN (n = 16) and the control group (n = 13) on admission
      were: age: 15.0 +/- 1.7 vs. 15.2 +/- 1.4 years, p = 0.7; body mass index (BMI):
      15.5 +/- 2.3 vs. 19.8 +/- 2.9 kg/m2, p < 0.001; venous pH 7.34 +/- 0.02 vs. 7.38
      +/- 0.03, p < 0.001; PCO2 53.3 +/- 4.1 vs. 42.5 +/- 3.1 mm Hg, p < 0.001; and
      HCO3 28.7 +/- 2.0 vs. 25.3 +/- 2.4 meq/L, p < 0.001, respectively. There were no
      significant differences in nocturnal respiratory rates, pulse-oximetry oxygen
      saturations, or end-tidal CO2. Pulmonary function tests (PFTs) in adolescents
      with AN revealed no obstructive, restrictive, or significant pulmonary vascular
      disease except for lower peak expiratory flow rates (PEFRs). During
      hospitalization (12.3 +/- 3.8 days), their weight, BMI, mean nocturnal heart
      rate, and respiratory rate increased significantly, while their venous PCO2 and
      HCO3 decreased significantly without significant changes in PFTs. DISCUSSION:
      Adolescents with recent onset AN, admitted for medical stabilization, demonstrate
      hypercapnia despite normal PFTs, except for decreased PEFRs. These could result
      from decreased respiratory muscle strength and/or abnormal control of breathing.

PMID- 21898520
TI  - On the association between variables with lower detection limits.
AB  - In this paper, we define a modified version tau(b) of Kendall's tau to measure
      the association in a pair (X,Y) of random variables subject to fixed left
      censoring due to known lower detection limits. We provide a nonparametric
      estimator of tau(b) and investigate its asymptotic properties. We then assume an
      Archimedean copula for (X,Y) and express tau(b) in terms of the copula parameter
      alpha and the censoring fractions. We deduce estimators for alpha and for the
      global Kendall's tau. We develop a goodness-of-fit test for the assumed copula.
      We evaluate the finite-sample performance of the proposed methods by simulations
      and illustrate their use with a real data set on plasma and saliva viral loads.

PMID- 21898521
TI  - Estimating treatment effect via simple cross design synthesis.
AB  - Randomized controlled trials (RCTs) are the traditional gold standard evidence
      for medical decision-making. However, protocols that limit enrollment eligibility
      introduce selection error that severely limits a RCT's applicability to a wide
      range of patients. Conversely, high quality observational data can be
      representative of entire populations, but freedom to choose treatment can bias
      estimators based on this data. Cross design synthesis (CDS) is an approach to
      combining both RCT and observational data in a single analysis that capitalizes
      on the RCT's strong internal validity and the observational study's strong
      external validity. We proposed and assessed a simple estimator of effect size
      based on the CDS approach. We evaluated its properties within a formal framework
      of causal estimation and compared our estimator with more traditional estimators
      based on single sources of evidence. We show that under ideal conditions the
      simple CDS estimator is unbiased whenever the observational data-based
      estimators' treatment selection error is constant across those who are and are
      not eligible for RCT participation. Whereas this assumption may not often hold in
      practice, assumptions required for the unbiasedness of usual single-source
      estimators may also be implausible. We show that, under some reasonable data
      assumptions, our simple CDS estimator has smaller bias and better coverage than
      commonly used estimates based on randomized or observational studies alone.

PMID- 21898522
TI  - Conditional predictive inference for online surveillance of spatial disease
      incidence.
AB  - This paper deals with the development of statistical methodology for timely
      detection of incident disease clusters in space and time. The increasing
      availability of data on both the time and the location of events enables the
      construction of multivariate surveillance techniques, which may enhance the
      ability to detect localized clusters of disease relative to the surveillance of
      the overall count of disease cases across the entire study region. We introduce
      the surveillance conditional predictive ordinate as a general Bayesian model
      based surveillance technique that allows us to detect small areas of increased
      disease incidence when spatial data are available. To address the problem of
      multiple comparisons, we incorporate a common probability that each small area
      signals an alarm when no change in the risk pattern of disease takes place into
      the analysis. We investigate the performance of the proposed surveillance
      technique within the framework of Bayesian hierarchical Poisson models using a
      simulation study. Finally, we present a case study of salmonellosis in South
      Carolina.

PMID- 21898523
TI  - Time-to-event analysis with treatment arm selection at interim.
AB  - This paper discusses the application of an adaptive design for treatment arm
      selection in an oncology trial, with survival as the primary endpoint and disease
      progression as a key secondary endpoint. We carried out treatment arm selection
      at an interim analysis by using Bayesian predictive power combining evidence from
      the two endpoints. At the final analysis, we carried out a frequentist
      statistical test of efficacy on the survival endpoint. We investigated several
      approaches (Bonferroni approach, 'Dunnett-like' approach, a conditional error
      function approach and a combination p-value approach) with respect to their power
      and the precise conditions under which type I error control is attained.

PMID- 21898525
TI  - Inference for cumulative incidence quantiles via parametric and nonparametric
      approaches.
AB  - In survival analysis, a point estimate and confidence interval for median
      survival time have been frequently used to summarize the survival curve. However,
      such quantile analyses on competing risks data have not been widely investigated.
      In this paper, we propose parametric inferences for quantiles from the cumulative
      incidence function and develop parametric confidence intervals for quantiles. In
      addition, we study a simplified method of inference for the nonparametric
      approach. We compare the parametric and nonparametric inferences in empirical
      studies. Simulation studies show that the procedures perform well, with
      parametric analyses yielding smaller mean square error when the model is not too
      badly misspecified. We illustrate the methods with data from a breast cancer
      clinical trial.

PMID- 21898524
TI  - Analysis of non-ignorable missing and left-censored longitudinal data using a
      weighted random effects tobit model.
AB  - In a longitudinal study with response data collected during a hospital stay,
      observations may be missing because of the subject's discharge from the hospital
      prior to completion of the study or the death of the subject, resulting in non
      ignorable missing data. In addition to non-ignorable missingness, there is left
      censoring in the response measurements because of the inherent limit of
      detection. For analyzing non-ignorable missing and left-censored longitudinal
      data, we have proposed to extend the theory of random effects tobit regression
      model to weighted random effects tobit regression model. The weights are computed
      on the basis of inverse probability weighted augmented methodology. An extensive
      simulation study was performed to compare the performance of the proposed model
      with a number of competitive models. The simulation study shows that the
      estimates are consistent and that the root mean square errors of the estimates
      are minimal for the use of augmented inverse probability weights in the random
      effects tobit model. The proposed method is also applied to the non-ignorable
      missing and left-censored interleukin-6 biomarker data obtained from the Genetic
      and Inflammatory Markers of Sepsis study.

PMID- 21898526
TI  - Characterization of proteins by ambient mass spectrometry.
AB  - Proteins play important roles in living systems and are topics of many
      fundamental and applied research projects. With the introduction of electrospray
      ionization and matrix-assisted laser desorption/ionization for analysis of
      biomacromolecules in the late 1980s, mass spectrometry has become an important
      tool for characterization of proteins. Characterization of proteins in raw
      samples by these mass spectrometric techniques, however, usually requires
      extensive sample pretreatment. Ambient ionization techniques are new mass
      spectrometric techniques that allow direct analysis of samples with no or little
      sample preparation. Can these techniques facilitate or even eliminate sample
      preparation for mass spectrometric analysis of proteins? Apart from sample
      preparation, do these techniques offer any new features for characterization of
      proteins as compared with conventional ESI or MALDI? Recent advances in
      characterization of proteins by ambient mass spectrometry are summarized and
      commented in this article.

PMID- 21898527
TI  - Antileukaemia effect of rapamycin alone or in combination with daunorubicin on
      Ph+ acute lymphoblastic leukaemia cell line.
AB  - The translocation (9;22) (q34;q11), known as the Philadelphia (Ph) chromosome and
      bcr-abl fusion gene, is the common cytogenetic abnormality and an unfavourable
      prognosis in adult acute lymphoblastic leukaemia (ALL). Although chemotherapeutic
      treatment produced high rates of complete response in approximately 70%-80% of
      newly diagnosed Ph+ ALL, the onset of resistance and clinical relapse is rapid.
      Therefore, the efficacy of treatment in Ph+ ALL is still to be determined. In
      this study, we aimed to assess the antileukemic activity of rapamycin (RAPA)
      (Sigma-Aldrich Corporation, MO, USA), a mammalian target of rapamycin inhibitor,
      alone and in combination with daunorubicin (DNR) (Pharmacia & Upjohn Company,
      Germany) in a Ph+ acute lymphoblastic cell line SUP-B15 and a primary Ph+ ALL
      sample in vitro. Here, we demonstrated that 50 nmol/L of RAPA significantly
      intensified the inhibition induced by DNR on both Ph+ ALL cell line and a primary
      Ph+ ALL sample. Notably, we reported that the consequence of DNR treatment
      induced the over expression of the components of mammalian target of rapamycin
      signalling pathway, whereas RAPA effectively eliminated this deleterious side
      effect of DNR, which might enhance DNR's ability to kill drug-resistant cancer.
      The synergistic effect was also associated with the increase in autophagy,
      blockage of cell cycle progression in the G1 phase. Altogether, our results
      suggest that DNR in combination with RAPA is more effective in the treatment of
      Ph+ ALL compared with DNR alone.

PMID- 21898528
TI  - Bone marrow trephine biopsy findings in myeloma with small-lymphoid cells and
      CCND1 translocation.

PMID- 21898529
TI  - Cancer-testis antigen expression and its epigenetic modulation in acute myeloid
      leukemia.
AB  - Cancer-testis antigens (CTA) represent attractive targets for tumor
      immunotherapy. However, a broad picture of CTA expression in acute myeloid
      leukemia (AML) is missing. CTA expression was analyzed in normal bone marrow (BM)
      as well as in AML cell lines before and after treatment with demethylating agents
      and/or histone acetylase inhibitors. Presence of selected CTA with a strictly
      tumor-restricted expression was then determined in samples of patients with AML
      before and after demethylating therapy. Screening AML cell lines for the
      expression of 20 CTA, we identified six genes (MAGE-A3, PRAME, ROPN1, SCP-1,
      SLLP1, and SPO11) with an AML-restricted expression. Analyzing the expression of
      these CTA in blast-containing samples from AML patients (N = 64), we found all
      samples to be negative for MAGE-A3 and SPO11 while a minority of patients
      expressed ROPN1 (1.6%), SCP-1 (3.1%), or SLLP1 (9.4%). The only CTA expressed in
      substantial proportion of patients (53.1%) was PRAME. Following demethylating
      treatment with 5'-aza-2'-deoxycytidine, we observed an increased or de novo
      expression of CTA, in particular of SSX-2, in AML cell lines. In AML patients, we
      detected increased expression of PRAME and induction of SSX-2 after demethylating
      therapy with 5-azacytidine. With the exception of PRAME, CTA are mostly absent
      from AML blasts. However, demethylating treatment induces strong expression of
      CTA, particularly of SSX-2, in vitro and in vivo. Therefore, we propose that CTA
      specific immunotherapy for AML should preferentially target PRAME and/or should
      be combined with the application of demethylating agents opening the perspective
      for alternative targets like CTA SSX-2.

PMID- 21898530
TI  - Stroke recurrence in children with sickle cell disease treated with hydroxyurea
      following first clinical stroke.
AB  - Chronic transfusion therapy is the treatment of choice for preventing stroke
      recurrence in children with sickle cell disease (SCD). The majority of children
      affected by this devastating complication live in the developing world where
      access to regular blood transfusions may be impractical. Since 2000, in the
      absence of regular blood supplies, all children at the Sickle Cell Unit who had
      experienced a first clinical stroke were offered hydroxyurea (HU) as the only
      intervention to prevent stroke recurrence. Forty-four children were identified as
      having experienced a first clinical stroke between January 1, 2000 and September
      30, 2009; one died at that presentation. Forty-three children were therefore
      followed for 111 person-years, of whom 10 (23.3%) agreed to start HU. Only one
      child in the HU group, incidence rate 2/100 person-years, had clinical stroke
      recurrence, compared to 20/33 in the non-HU group, incidence rate 29/100 person
      years (Hazard ratio (HR) 9.4 [95% Confidence interval (CI): 1.3-70.6]; P = 0.03).
      When the groups were compared, in the non-HU group, four died (vs. zero), 13 (53%
      vs. 10%) had moderate-severe physical disability (P = 0.017), and 12 (44% vs.
      20%) required special education or were too disabled to attend school. Our data
      support the role of HU as a useful intervention for prevention of stroke
      recurrence in SCD when transfusion programs are not available or practical.

PMID- 21898531
TI  - Non-Hodgkin lymphoma of the prostate.

PMID- 21898532
TI  - Efficacy and toxicity of a rituximab and methotrexate based regimen (GMALL B
      ALL/NHL 2002 protocol) in Burkitt's and primary mediastinal large B-cell
      lymphoma.
AB  - There have been several attempts to improve treatment and outcome of patients
      with primary mediastinal B-cell lymphoma (PMBL) and Burkitt's lymphoma (BL). In
      recent years, chemotherapy dose intensification and the addition of rituximab
      have led to a remarkable progress and have developed into integral parts of
      treatment for both entities of lymphoma [1-4]. Here, we report our monocenter
      results of a high-dose methotrexate based alternating regimen with rituximab (B
      ALL/NHL 2002 protocol) in 15 patients with PMBL and 28 patients with sporadic BL.
      Since the early 1980s, protocols of GMALL have been continuously adapted and in
      the meantime they have become reference treatment for BL and B-ALL in Germany.
      The latest changes comprised the additional use of rituximab, standardized G-CSF
      support,implementation of high-dose cytarabine, intrathecal triple therapy,and
      age-adjusted stratification. Furthermore, we additionally amended supportive care
      with palifermin as it reduced severity and prevalence of mucositis [5].

PMID- 21898533
TI  - The source of chilopod sensory information: external structure and distribution
      of antennal sensilla in Scutigera coleoptrata (chilopoda, Scutigeromorpha).
AB  - The investigation of the antennae of Scutigera coleoptrata (Linnaeus, 1758) by
      scanning electron microscopy (SEM) revealed the presence of five types of
      sensilla: sensilla trichodea, beak-like sensilla, cone-shaped sensilla
      brachyconica on the terminal article, sensory cones at the antennal nodes, and
      the shaft organ. Alongside the presence and absence of antennal sensillar types,
      three unique characters were found in the Scutigeromorpha: the presence of long
      antennae with nodes bearing sensory cones, the presence of a bipartite shaft
      including the shaft organ, and the presence of beak-like sensilla.
      Neuroanatomical data showed that the animals' brains are equipped with well
      developed primary olfactory and mechanosensory centers, suggesting that the
      antennae must be equipped with specialized sensilla to perceive chemosensory and
      mechanosensory cues. With the evidence provided in this article for the
      Scutigeromorpha, SEM data are available at last on the antennal sensilla for all
      five chilopod taxa, allowing a comparative discussion of antennal morphology in
      Chilopoda.

PMID- 21898534
TI  - Trends in stroke hospitalizations and associated risk factors among children and
      young adults, 1995-2008.
AB  - OBJECTIVE: The aim of this study was to determine acute stroke hospitalization
      rates for children and young adults and the prevalence of stroke risk factors
      among children and young adults hospitalized for acute stroke. METHODS: The study
      population consisted of 1995-2008 hospitalizations from the Nationwide Inpatient
      Sample of the Healthcare Cost and Utilization Project. Subarachnoid hemorrhage,
      intracerebral hemorrhage, and ischemic stroke hospitalizations were identified by
      the primary International Classification of Diseases, 9th ed, Clinical
      Modification (ICD-9-CM) code. Seven consecutive 2-year time intervals were
      selected. Three age groups were utilized: 5 to 14 years, 15 to 34 years, and 35
      to 44 years. Stroke risk factors and comorbidities among those hospitalized with
      acute stroke were identified by secondary ICD-9-CM codes. RESULTS: During the
      period of study, the prevalence of hospitalizations of acute ischemic stroke
      increased among all age and gender groups except females aged 5 to 14 years.
      Females aged 15 to 34 years and males and females aged 35 to 44 years showed a
      decrease in the prevalence of hospitalizations for subarachnoid hemorrhage,
      whereas females aged 5 to 14 years showed increases for subarachnoid hemorrhage.
      Hypertension, diabetes, obesity, lipid disorders, and tobacco use were among the
      most common coexisting conditions, and their prevalence increased from 1995 to
      2008 among adolescents and young adults (aged 15-44 years) hospitalized with
      acute ischemic stroke. INTERPRETATION: Increases in the prevalence of ischemic
      stroke hospitalizations and coexisting traditional stroke risk factors and health
      risk behaviors were identified among acute ischemic stroke hospitalizations in
      young adults. Our results from national surveillance data accentuate the need for
      public health initiatives to reduce risk factors for stroke among adolescents and
      young adults.

PMID- 21898535
TI  - LPS induces phosphorylation of actin-regulatory proteins leading to actin
      reassembly and macrophage motility.
AB  - Upon bacterial infection lipopolysaccharide (LPS) induces migration of
      monocytes/macrophages to the invaded region and production of pro-inflammatory
      mediators. We examined mechanisms of LPS-stimulated motility and found that LPS
      at 100 ng/ml induced rapid elongation and ruffling of macrophage-like J774 cells.
      A wound-healing assay revealed that LPS also activated directed cell movement
      that was followed by TNF-alpha production. The CD14 and TLR4 receptors of LPS
      translocated to the leading lamella of polarized cells, where they transiently
      colocalized triggering local accumulation of actin filaments and
      phosphatidylinositol 4,5-bisphosphate. Fractionation of Triton X-100 cell lysates
      revealed that LPS induced polymerization of cytoskeletal actin filaments by 50%,
      which coincided with the peak of cell motility. This microfilament population
      appeared at the expense of short filaments composing the plasma membrane skeleton
      of unstimulated cells and actin monomers consisting prior to the LPS stimulation
      about 60% of cellular actin. Simultaneously with actin polymerization, LPS
      stimulated phosphorylation of two actin-regulatory proteins, paxillin on tyrosine
      118 by 80% and N-WASP on serine 484/485 by 20%, and these events preceded
      activation of NF-kappaB. LPS-induced protein phosphorylation and reorganization
      of the actin cytoskeleton were inhibited by PP2, a drug affecting activity of
      tyrosine kinases of the Src family. The data indicate that paxillin and N-WASP
      are involved in the reorganization of actin cytoskeleton driving motility of LPS
      stimulated cells. Disturbances of actin organization induced by cytochalasin D
      did not inhibit TNF-alpha production suggesting that LPS-induced cell motility is
      not required for TNF-alpha release.

PMID- 21898537
TI  - Xanthohumol-supplemented beer modulates angiogenesis and inflammation in a skin
      wound healing model. Involvement of local adipocytes.
AB  - Angiogenesis and inflammation are two intermingled processes that play a role in
      wound healing. Nevertheless, whenever exacerbated, these processes result in
      nonhealing wounds. Xanthohumol (XN), a beer-derived polyphenol, inhibits these
      processes in many physiopathological situations. This study aimed at examining
      whether XN ingestion affects wound healing. Wistar rats drinking water, 5%
      ethanol, stout beer (SB) or stout beer supplemented with 10 mg/L XN (Suppl SB)
      for 4 weeks, were subjected to a 1.5 cm full skin-thickness longitudinal
      incision, and further maintained under the same beverage conditions for another
      week. No differences in beverage consumption or body weight were found throughout
      the study but food intake decreased in every group relative to controls.
      Consumption of Suppl SB resulted in decreased serum VEGF levels (18.42%), N
      acetylglucosaminidase activity (27.77%), IL1beta concentration (9.07%), and NO
      released (77.06%), accompanied by a reduced redox state as observed by increased
      GSH/GSSG ratio (to 198.80%). Also, the number of blood vessels within the wound
      granulation tissue seems to reduce in animals drinking Suppl SB (23.08%).
      Interestingly, SB and primarily Suppl SB showed a tendency to increase adipocyte
      number (to 194.26% and 156.68%, respectively) and reduce adipocyte size (4.60%
      and 24.64%, respectively) within the granuloma. Liver function and metabolism did
      not change among the animal groups as analyzed by plasma biochemical parameters,
      indicating no beverage toxicity. This study shows that XN intake in its natural
      beer context reduced inflammation, oxidative stress, and angiogenesis,
      ameliorating the wound healing process, suggesting that this polyphenol may exert
      beneficial effect as a nutritional supplement.

PMID- 21898536
TI  - Oophorectomy-induced bone loss is attenuated in MAGP1-deficient mice.
AB  - Microfibril-associated glycoprotein-1 (MAGP1), together with the fibrillins, are
      constitutive components of vertebrate microfibrils. Mice deficient in MAGP1
      (murine MAGP1 knockout animals (Mfap2(-/-)); MAGP1Delta) is appropriate develop
      progressive osteopenia and reduced whole bone strength, and have elevated numbers
      of osteoclasts lining the bone surface. Our previous studies suggested that the
      increased osteoclast population was associated with elevated levels of receptor
      activator of NF-kappaB ligand (RANKL), a positive regulator of osteoclast
      differentiation. To explore the relationship between RANKL expression and
      osteoclast differentiation in MAGP1 deficiency, oophorectomy (OVX) was used to
      stimulate RANKL expression in both WT and MAGP1Delta animals. Bone loss following
      OVX was monitored using whole body DEXA and in vivo uCT. While WT mice exhibited
      significant bone loss following OVX, percent bone loss was reduced in MAGP1Delta
      mice. Further, serum RANKL levels rose significantly in OVX WT mice, whereas,
      there was only a modest increase in RANKL following OVX in the mutant mice due to
      already high baseline levels. Elevated RANKL expression was normalized when
      cultured MAGP1Delta osteoblasts were treated with a neutralizing antibody
      targeting free TGFbeta. These studies provide support for increased RANKL
      expression associated with MAGP1 deficiency and provide a link to altered TGF
      beta signaling as a possible causative signaling pathway regulating RANKL
      expression in MAGP1Delta osteoblasts.

PMID- 21898538
TI  - The box A domain of high mobility group box-1 protein as an efficient siRNA
      carrier with anti-inflammatory effects.
AB  - High mobility group box-1 (HMGB-1) is a DNA binding nuclear protein and pro
      inflammatory cytokine. The box A domain of HMGB-1 (rHMGB-1A) exerts an anti
      inflammatory effect, inhibiting wild-type HMGB-1 (wtHMGB-1). In this study, HMGB
      1A was evaluated as an siRNA carrier with anti-inflammatory effects. HMGB-1A was
      expressed and purified by consecutive nickel chelate chromatography, cationic
      exchange chromatography, and polymixin B chromatography. Purified rHMGB-1A
      demonstrated an anti-inflammatory effect, reducing tumor necrosis factor-alpha
      (TNF-alpha) in wtHMGB-1 or lipopolysaccharide (LPS) activated macrophages. In gel
      retardation assay, rHMGB-1A formed a stable complex with siRNA at or above a 1:2
      weight ratio (siRNA:rHMGB-1A). A heparin competition assay showed that an
      siRNA/rHMGB-1A complex released siRNA more easily than an siRNA/polyethylenimine
      (PEI, 25 kDa) complex. Luciferase siRNA/rHMGB-1A reduced firefly luciferase
      expression at a similar level as luciferase siRNA/PEI complex. Furthermore, TNF
      alpha siRNA/rHMGB-1A synergistically reduced TNF-alpha expression in LPS
      activated macrophages. Therefore, rHMGB-1A may be useful as an siRNA carrier with
      anti-inflammatory effects in siRNA therapy for various inflammatory diseases.

PMID- 21898539
TI  - Regulation of anti-apoptotic BCL2-proteins by non-canonical interactions: the
      next step forward or two steps back?
AB  - All aspects of cellular biology affect the process of regulated cell death, or
      apoptosis, and disruption of this process is a causative event in many diseases.
      Therefore, a comprehensive understanding of all pathways that regulate apoptosis
      would increase our knowledge of basic cellular functions, as well as the
      etiologies of many diseases. In turn, we may be able to use this knowledge to
      better treat patients with diseases, including cancer. Although the basic
      signaling pathway that regulates apoptosis has been known for over 10 years, we
      still have much to learn about the upstream signaling components that can
      directly regulate the core apoptosis machinery. The focus of this review will be
      to direct attention to non-canonical regulators of the BCL2-family of proteins,
      especially our void of understanding of such interactions, and the controversy
      that surrounds some such interactions.

PMID- 21898540
TI  - Broader utilization of origins of DNA replication in cancer cell lines along a 78
      kb region of human chromosome 2q34.
AB  - Human DNA replication depends on the activation of thousands of origins
      distributed within the genome. The actual distribution of origins is not known,
      nor whether this distribution is unique to a cell type, or if it changes with the
      proliferative state of the cell. In this study, we have employed a real-time PCR
      based nascent strand DNA abundance assay, to determine the location of origins
      along a 78 kb region on Chr2q34. Preliminary studies using nascent DNA strands
      isolated from either HeLa and normal skin fibroblast cells showed that in both
      cell lines peaks of high origin activity mapped in similar locations. However,
      the overall origin profile in HeLa cells corresponded to broad origin activation
      zones, whereas in fibroblasts a more punctuated profile of origin activation was
      observed. To investigate the relevance of this differential origin profile, we
      compared the origin distribution profiles in breast cancer cell lines MDA-MB-231,
      BT-474, and MCF-7, to their normal counterpart MCF-10A. In addition, the CRL7250
      cell line was also used as a normal control. Our results validated our earlier
      observation and showed that the origin profile in normal cell lines exhibited a
      punctuated pattern, in contrast to broader zone profiles observed in the cancer
      cell lines. A quantitative analysis of origin peaks revealed that the number of
      activated origins in cancer cells is statistically larger than that obtained in
      normal cells, suggesting that the flexibility of origin usage is significantly
      increased in cancer cells compared to their normal counterparts.

PMID- 21898541
TI  - Hedgehog signaling and osteoblast gene expression are regulated by purmorphamine
      in human mesenchymal stem cells.
AB  - Several biological events are controlled by Hedgehog (Hh) signaling, including
      osteoblast phenotype development. This study aimed at evaluating the gene
      expression profile of human mesenchymal stem cells (hMSCs) treated with the Hh
      agonist, purmorphamine, focusing on Hh signaling and osteoblast differentiation.
      hMSCs from bone marrow were cultured in non-osteogenic medium with or without
      purmorphamine (2 uM) for periods of up to 14 days. Purmorphamine up-regulated
      gene expression of the mediators of Hh pathway, SMO, PTCH1, GLI1, and GLI2. The
      activation of Hh pathway by purmorphamine increased the expression of several
      genes (e.g., RUNX2 and BMPs) related to osteogenesis. Our results indicated that
      purmorphamine triggers Hh signaling pathway in hMSCs, inducing an increase in the
      expression of a set of genes involved in the osteoblast differentiation program.
      Thus, we conclude that Hh is a crucial pathway in the commitment of
      undifferentiated cells to the osteoblast lineage.

PMID- 21898542
TI  - Cyclin D3 promotes myogenic differentiation and Pax7 transcription.
AB  - Differentiation of skeletal muscle myoblasts involves activation of muscle
      specific markers such as MyoD, Myf5, MRF4, and myogenin, followed by exit from
      the cell cycle, expression of structural proteins, and fusion into multinucleated
      myotubes. Cyclin D3 is upregulated during muscle differentiation, and expression
      of cyclin D3 in proliferating myoblasts causes early activation of myogenesis. In
      this study, we have identified the genes activated by cyclin D3 expression in
      C2C12 myoblasts and differentiated cells by real-time PCR analysis. Cyclin D3
      expression induced faster differentiation kinetics and increase in levels of
      myogenic genes such as MyoD, Myf5, and myogenin at an early stage during the
      differentiation process, although long-term myogenic differentiation was not
      affected. Transcript levels of the transcription factor Pax7 that is expressed in
      muscle progenitors were enhanced by cyclin D3 expression in myoblasts. Components
      of a histone methyltransferase complex recruited by Pax7 to myogenic gene
      promoters were also regulated by cyclin D3. Further, the Pax7 promoter was
      upregulated in myoblasts expressing cyclin D3. Myoblasts that expressed cyclin D3
      showed moderately higher levels of the cyclin-dependent kinase inhibitor p21 and
      were stalled in G2/M phase of the cell cycle. Our findings suggest that cyclin D3
      primes myoblasts for differentiation by enhancing muscle specific gene expression
      and cell cycle exit.

PMID- 21898544
TI  - The role of Kupffer cells in rat liver regeneration revealed by cell-specific
      microarray analysis.
AB  - Liver regeneration after partial hepatectomy is a process with various types of
      cells involved. The role of Kupffer cells (KCs) in liver regeneration is still
      controversial. In this study we isolated KCs from regenerating liver and
      conducted cell-specific microarray analysis. The results demonstrated that the
      controversial role of KCs in liver regeneration could be explained with the
      expression patterns of TGF-alpha, IL-6, TNF, and possibly IL-18 during liver
      regeneration. IL-18 may play an important role in negative regulation of liver
      regeneration. The functional profiles of gene expression in KCs also indicated
      that KC signaling might play a negative role in cell proliferation: signaling
      genes were down regulated before cell division. Immune response genes in KCs were
      also down regulated during liver regeneration, demonstrating similar expression
      profiles to that of hepatocytes. The expression patterns of key genes in these
      functional categories were consistent with the temporal functional profiles.

PMID- 21898543
TI  - Erythropoietin mediated bone formation is regulated by mTOR signaling.
AB  - The role of erythropoietin (Epo) and Epo/Epo receptor (EpoR) signaling pathways
      for production of red blood cells are well established. However, little is known
      about Epo/EpoR signaling in non-hematopoietic cells. Recently, we demonstrated
      that Epo activates JAK/STAT signaling in hematopoietic stem cells (HSCs), leading
      to the production of bone morphogenetic protein 2 (BMP2) and bone formation and
      that Epo also directly activates mesenchymal cells to form osteoblasts in vitro.
      In this study, we investigated the effects of mTOR signaling on Epo-mediated
      osteoblastogenesis and osteoclastogenesis. We found that mTOR inhibition by
      rapamycin blocks Epo-dependent and -independent osteoblastic phenotypes in human
      bone marrow stromal cells (hBMSCs) and ST2 cells, respectively. Furthermore, we
      found that rapamycin inhibits Epo-dependent and -independent osteoclastogenesis
      in mouse bone marrow mononuclear cells and Raw264.7 cells. Finally, we
      demonstrated that Epo increases NFATc1 expression and decreases cathepsin K
      expression in an mTOR-independent manner, resulting in an increase of osteoclast
      numbers and a decrease in resorption activity. Taken together, these results
      strongly indicate that mTOR signaling plays an important role in Epo-mediated
      bone homeostasis.

PMID- 21898545
TI  - CD109-mediated degradation of TGF-beta receptors and inhibition of TGF-beta
      responses involve regulation of SMAD7 and Smurf2 localization and function.
AB  - Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that
      regulates a wide variety of cellular processes including proliferation,
      differentiation, and extracellular matrix deposition. Dysregulation of TGF-beta
      signaling is associated with several diseases such as cancer and tissue fibrosis.
      TGF-beta signals through two transmembrane proteins known as the type I (TGFBR1)
      and type II (TGFBR2) receptors. The levels of these receptors at the cell surface
      are tightly regulated by several mechanisms, including degradation following
      recruitment of the E3 ubiquitin ligase SMAD ubiquitination regulatory factor
      (Smurf) 2 by SMAD7. In addition, TGF-beta co-receptors can modulate TGF-beta
      signaling receptor activity in a cell-specific manner. We have previously
      identified a novel TGF-beta co-receptor, CD109, a glycosyl phosphatidylinositol
      (GPI)-anchored protein that negatively regulates TGF-beta signaling. Despite
      CD109's potential relevance as a regulator of TGF-beta action in vivo, the
      mechanisms by which CD109 regulates TGF-beta signaling are still incompletely
      understood. Previously, we have shown that CD109 downregulates TGF-beta signaling
      by promoting TGF-beta receptor localization into the lipid raft/caveolae
      compartment and by enhancing TGF-beta receptor degradation. Here, we demonstrate
      that CD109 enhances SMAD7/Smurf2-mediated degradation of TGFBR1 in a ligand
      dependent manner. Moreover, we show that CD109 regulates the localization and the
      association of SMAD7/Smurf2 with TGFBR1. Finally, we demonstrate that CD109's
      inhibitory effect on TGF-beta signaling and responses require SMAD7 expression
      and Smurf2 ubiquitin ligase activity. Taken together, these results suggest that
      CD109 is an important regulator of SMAD7/Smurf2-mediated degradation of TGFBR1.

PMID- 21898546
TI  - The Wnt/beta-catenin signaling pathway: a potential therapeutic target in the
      treatment of triple negative breast cancer.
AB  - Breast cancer continues to be a serious health problem particularly in developed
      countries. Of particular concern is triple negative breast cancer (TNBC) which
      does not respond well to standard hormone therapy and is associated with poor
      overall patient prognosis. Recent studies indicate that Wnt/beta-catenin
      signaling is particularly activated in TNBC, such that the Wnt receptor frizzled
      7 (FZD7) and the Wnt co-receptor LRP6 were found to be up regulated in TNBC. In
      addition, it has been demonstrated that transcriptional knockdown of LRP6 or FZD7
      in TNBC cells suppressed tumor growth in vivo. Furthermore, salinomycin, a
      selective breast cancer stem cell killer, was recently demonstrated to be an
      inhibitor of Wnt/beta-catenin signaling by inducing LRP6 degradation. Therefore,
      the Wnt/beta-catenin signaling pathway and particularly the Wnt receptors on the
      cell surface may serve as novel therapeutic targets for the treatment of TNBC.

PMID- 21898547
TI  - Osteoblastogenesis and osteoprotection enhanced by flavonolignan silibinin in
      osteoblasts and osteoclasts.
AB  - Bone-remodeling imbalance induced by decreased osteoblastogenesis and increased
      bone resorption is known to cause skeletal diseases such as osteoporosis.
      Silibinin is the major active constituent of silymarin, the mixture of
      flavonolignans extracted from blessed milk thistle (Silybum marianum). Numerous
      studies suggest that silibinin is a powerful antioxidant and has anti-hepatotoxic
      properties and anti-cancer effects against carcinoma cells. This study
      investigated that silibinin had bone-forming and osteoprotective effects in in
      vitro cell systems of murine osteoblastic MC3T3-E1 cells and RAW 264.7 murine
      macrophages. MC3T3-E1 cells were incubated in osteogenic media in the presence of
      1-20 uM silibinin up to 15 days. Silibinin accelerated cell proliferation and
      promoted matrix mineralization by enhancing bone nodule formation by calcium
      deposits. In addition, silibinin furthered the induction of osteoblastogenic
      biomarkers of alkaline phosphatase, collagen type 1, connective tissue growth
      factor, and bone morphogenetic protein-2. Differentiated MC3T3-E1 cells enhanced
      secretion of receptor activator of nuclear factor-kappaB ligand (RANKL) essential
      for osteoclastogenesis, which was reversed by silibinin. On the other hand, RAW
      264.7 cells were pre-incubated with 1-20 uM silibinin for 5 days in the presence
      of RANKL. Non-toxic silibinin markedly attenuated RANK transcription and
      intracellular adhesion molecule-1 expression elevated by RANKL, thereby
      suppressing the differentiation of macrophages to multi-nucleated osteoclasts. It
      was also found that silibinin retarded tartrate-resistant acid phosphatase and
      cathepsin K induction and matrix metalloproteinase-9 activity elevated by RANKL
      through disturbing TRAF6-c-Src signaling pathways. These results demonstrate that
      silibinin was a potential therapeutic agent promoting bone-forming
      osteoblastogenesis and encumbering osteoclastic bone resorption.

PMID- 21898548
TI  - T cell-mediated increased osteoclast formation from peripheral blood as a
      mechanism for Crohn's disease-associated bone loss.
AB  - The pathophysiology of osteoporosis in patients with Crohn's disease (CD) is
      still not completely elucidated. In this study, we evaluated osteoclastogenesis
      from peripheral blood cells of CD patients and studied the role of lymphocytes
      and inflammatory cytokines in this process. Peripheral blood mononuclear cells
      from seven patients with quiescent CD and matched healthy controls were isolated,
      and separated into T cells, B cells, and a T- and B-cell depleted fraction. In
      various culture combinations, osteoclast formation in the absence of the
      osteoclastogenic factors RANKL and M-CSF was assessed by scoring the number of
      tartrate-resistant acid phosphatase (TRACP) positive multinucleated cells (MNCs).
      Cytokine levels in culture supernatants were measured. Formation of heterogeneous
      cell clusters in culture was noticed; a process that was inhibited by anti-LFA-1.
      In CD cultures, mean cluster area was up to threefold higher than in control
      cultures, and shown to be induced by T cells. Over tenfold higher numbers of
      TRACP(+) MNCs were found in CD cultures, but exclusively in cultures containing T
      cells. Formation of cell clusters correlated strongly with formation of TRACP(+)
      MNCs. Both cell cluster formation and osteoclast formation were related to IL-17
      levels in vitro. In conclusion, osteoclastogenesis, preceded by cell cluster
      formation, is T cell-mediated and increased in patients with quiescent CD. Our
      findings suggest heterotypic interactions between osteoclast precursors and T
      cells to be a triggering step in osteoclast formation in CD. Furthermore, our
      results propose a possible role for IL-17 in osteoclastogenesis in CD patients,
      and as such in CD-associated bone loss.

PMID- 21898550
TI  - Amphibians at risk? Susceptibility of terrestrial amphibian life stages to
      pesticides.
AB  - Current pesticide risk assessment does not specifically consider amphibians.
      Amphibians in the aquatic environment (aquatic life stages or postmetamorphic
      aquatic amphibians) and terrestrial living juvenile or adult amphibians are
      assumed to be covered by the risk assessment for aquatic invertebrates and fish,
      or mammals and birds, respectively. This procedure has been evaluated as being
      sufficiently protective regarding the acute risk posed by a number of pesticides
      to aquatic amphibian life stages (eggs, larvae). However, it is unknown whether
      the exposure and sensitivity of terrestrial living amphibians are comparable to
      mammalian and avian exposure and sensitivity. We reviewed the literature on
      dermal pesticide absorption and toxicity studies for terrestrial life stages of
      amphibians, focusing on the dermal exposure pathway, that is, through treated
      soil or direct overspray. In vitro studies demonstrated that cutaneous absorption
      of chemicals is significant and that chemical percutaneous passage, P (cm/h), is
      higher in amphibians than in mammals. In vivo, the rapid and substantial uptake
      of the herbicide atrazine from treated soil by toads (Bufo americanus) has been
      described. Severe toxic effects on various amphibian species have been reported
      for field-relevant application rates of different pesticides. In general,
      exposure and toxicity studies for terrestrial amphibian life stages are scarce,
      and the reported data indicate the need for further research, especially in light
      of the global amphibian decline.

PMID- 21898549
TI  - p38 MAPK activation, JNK inhibition, neoplastic growth inhibition, and increased
      gap junction communication in human lung carcinoma and Ras-transformed cells by 4
      phenyl-3-butenoic acid.
AB  - Human lung neoplasms frequently express mutations that down-regulate expression
      of various tumor suppressor molecules, including mitogen-activated protein
      kinases such as p38 MAPK. Conversely, activation of p38 MAPK in tumor cells
      results in cancer cell cycle inhibition or apoptosis initiated by
      chemotherapeutic agents such as retinoids or cisplatin, and is therefore an
      attractive approach for experimental anti-tumor therapies. We now report that 4
      phenyl-3-butenoic acid (PBA), an experimental compound that reverses the
      transformed phenotype at non-cytotoxic concentrations, activates p38 MAPK in
      tumorigenic cells at concentrations and treatment times that correlate with
      decreased cell growth and increased cell-cell communication. H2009 human lung
      carcinoma cells and ras-transformed rat liver epithelial cells treated with PBA
      showed increased activation of p38 MAPK and its downstream effectors which
      occurred after 4 h and lasted beyond 48 h. Untransformed plasmid control cells
      showed low activation of p38 MAPK compared to ras-transformed and H2009 carcinoma
      cells, which correlates with the reduced effect of PBA on untransformed cell
      growth. The p38 MAPK inhibitor, SB203580, negated PBA's activation of p38 MAPK
      downstream effectors. PBA also increased cell-cell communication and connexin 43
      phosphorylation in ras-transformed cells, which were prevented by SB203580. In
      addition, PBA decreased activation of JNK, which is upregulated in many cancers.
      Taken together, these results suggest that PBA exerts its growth regulatory
      effect in tumorigenic cells by concomitant up-regulation of p38 MAPK activity,
      altered connexin 43 expression, and down-regulation of JNK activity. PBA may
      therefore be an effective therapeutic agent in human cancers that exhibit down
      regulated p38 MAPK activity and/or activated JNK and altered cell-cell
      communication.

PMID- 21898551
TI  - Validation of a chronic dietary cadmium bioaccumulation and toxicity model for
      Hyalella azteca exposed to field-contaminated periphyton and lake water.
AB  - A model previously developed in the laboratory to predict chronic bioaccumulation
      and toxicity of cadmium to Hyalella azteca from a diet of periphyton was
      validated by comparing predictions with measurements of Cd in two exposure
      scenarios: laboratory-cultured H. azteca exposed for 28 d to field-contaminated
      water and periphyton, and Cd measured in field-collected H. azteca. In both
      exposure scenarios, model predictions of bioaccumulation were shown to be robust;
      however, effects on Cd bioaccumulation from complexation with dissolved organic
      carbon (DOC) and inhibition of Cd bioaccumulation by Ca2+ must be incorporated
      into the model to permit its wider application. The model predicted that 80 to
      84% of Cd in H. azteca came from periphyton when H. azteca were chronically
      exposed to dissolved Cd in lake water at 2.63 to 3.01 nmol/L and periphyton at
      1,880 to 2,630 nmol/g ash-free dry mass. Dietary Cd contributed markedly to the
      model-predicted decrease in 28-d survival to 74% at environmental Cd
      concentrations in food and water. In reality, survival decreased to 10%. The
      lower than predicted survival likely was due to the higher nutritional quality of
      periphyton used to develop the model in the laboratory compared with the field
      collected periphyton. Overall, this research demonstrated that Cd in a periphyton
      diet at environmental concentrations can contribute to chronic toxicity in H.
      azteca.

PMID- 21898552
TI  - Reproductive changes in American kestrels (Falco sparverius) in relation to
      exposure to technical hexabromocyclododecane flame retardant.
AB  - Recently, the ban of hexabromocyclododecane (HBCD), a high-production-volume
      flame retardant, was announced in Europe and North America. However, the effects
      of HCBD remain understudied in birds. The objectives of the present comparative
      effects study were to determine whether exposure to an HBCD technical mixture
      (HBCD-TM) altered avian reproductive measures at an environmentally relevant
      concentration. American kestrels were exposed daily by food to HBCD-TM, i.e.,
      0.51 ug HBCD/g kestrel/d; exposed kestrels laid eggs that had alpha-HBCD
      concentrations (163.5 +/- 75.1 ng/g wet wt) tenfold greater than beta- and gamma
      HBCD isomers, an isomer profile and concentrations similar to those of eggs of
      wild peregrine falcons (Falco peregrinus). Concentrations of HBCD were not
      detected in the control kestrel eggs. In comparison with controls, the kestrels
      exposed to HBCD began to lay their eggs 6 d earlier and laid larger clutches of
      smaller eggs. The size of the eggs was inversely correlated with the in ovo alpha
      HBCD concentrations. The smaller eggs of the HBCD exposed kestrels also lost more
      weight by midincubation, suggesting increased eggshell porosity since eggshell
      thickness was comparable. Generally birds that lay more eggs and lay earlier in
      the breeding season gain the advantage of better hatching and fledging success,
      yet the kestrels exposed to HBCD failed to have better reproductive success than
      the control birds. These reproductive changes were a function of HBCD exposure,
      likely through changes in food consumption, with possible impacts on, for
      example, reproductive behavior and/or alterations in thyroid hormones.

PMID- 21898553
TI  - Identifying the causes of oil sands coke leachate toxicity to aquatic
      invertebrates.
AB  - A previous study found that coke leachates (CL) collected from oil sands field
      sites were acutely toxic to Ceriodaphnia dubia; however, the cause of toxicity
      was not known. Therefore, the purpose of this study was to generate CL in the
      laboratory to evaluate the toxicity response of C. dubia and perform chronic
      toxicity identification evaluation (TIE) tests to identify the causes of CL
      toxicity. Coke was subjected to a 15-d batch leaching process at pH 5.5 and 9.5.
      Leachates were filtered on day 15 and used for chemical and toxicological
      characterization. The 7-d median lethal concentration (LC50) was 6.3 and 28.7%
      (v/v) for pH 5.5 and 9.5 CLs, respectively. Trace element characterization of the
      CLs showed Ni and V levels to be well above their respective 7-d LC50s for C.
      dubia. Addition of ethylenediaminetetraacetic acid significantly (p <= 0.05)
      improved survival and reproduction in pH 5.5 CL, but not in pH 9.5 CL. Cationic
      and anionic resins removed toxicity of pH 5.5 CL only. Conversely, the toxicity
      of pH 9.5 CL was completely removed with an anion resin alone, suggesting that
      the pH 9.5 CL contained metals that formed oxyanions. Toxicity reappeared when Ni
      and V were added back to anion resin-treated CLs. The TIE results combined with
      the trace element chemistry suggest that both Ni and V are the cause of toxicity
      in pH 5.5 CL, whereas V appears to be the primary cause of toxicity in pH 9.5 CL.
      Environmental monitoring and risk assessments should therefore focus on the fate
      and toxicity of metals, especially Ni and V, in coke-amended oil sands
      reclamation landscapes.

PMID- 21898554
TI  - Characterization of lead induced metal-phytochelatin complexes in Chlamydomonas
      reinhardtii.
AB  - Accumulation of Pb and induction of phytochelatin synthesis were observed in
      Chlamydomonas reinhardtii upon Pb(II) exposure. Our aim was to examine whether
      Pb(II) is bound by phytochelatins (PCs) in C. reinhardtii and to examine formed
      complexes for their stoichiometry and composition. Metal-phytochelatin (Me-PC)
      complexes induced by Pb were isolated by size-exclusion chromatography in 13
      collected fractions, which were analyzed for their PC and metal content by high
      performance liquid chromatography and inductively coupled plasma mass
      spectrometry. A recovery of more than 90% of Pb from standard Pb-PC2 complexes
      within the total volume of the size-exclusion column indicated the adequacy of
      the method for Pb-PC(n) complex separation and characterization. Phytochelatins
      were detected mainly in a molecular weight ranging from 1,000 to 5,300 daltons
      (Da), indicating the formation of complexes with various stoichiometries.
      Approximately 72% of total PC2 eluted in the range from 1,000 to 1,600 Da, and
      80% of total PC3 eluted in the molecular weight range from 1,600 to 2,300 Da. The
      distribution of Cu, Zn, and Pb showed that more than 70% of these metals were
      associated with the high-molecular-weight fractions. Copper, zinc, and lead were
      also observed in PC-containing fractions, suggesting the formation of various Me
      PC complexes. The results of the present study indicate that the role of PCs in
      Pb detoxification is minor, because only 13% of total Pb was associated with PCs.

PMID- 21898555
TI  - Photodegradation of lambda-cyhalothrin and cypermethrin in aqueous solution as
      affected by humic acid and/or copper: intermediates and degradation pathways.
AB  - The influence of coexisting humic acids (HA) or Cu2+ on the photodegradation of
      pesticides lambda-cyhalothrin (lambda-CHT) and cypermethrin (CPM) in aqueous
      solution was studied under xenon lamp irradiation. The removal efficiency of
      pesticides lambda-CHT and CPM were enhanced in the presence of either Cu2+ or HA
      but restrained in the presence of both Cu2+ and HA. The photodegradation of
      lambda-CHT and CPM followed first-order reaction kinetics. The photodegradation
      intermediates of lambda-CHT and CPM were determined using gas chromatography/mass
      spectrometry. Possible photodegradation pathways included decarboxylation, ester
      bond cleavage, dechlorination, and phenyl group removal.

PMID- 21898556
TI  - Environmental concentrations of agricultural-use pesticide mixtures evoke primary
      and secondary stress responses in rainbow trout.
AB  - The present study sought to determine whether environmentally realistic mixtures
      of agriculturally important pesticides are stressful to fish. Juvenile rainbow
      trout were exposed for 96 h to concentrations of a pesticide mixture found in a
      waterway that is the focus of salmon restoration efforts (Nicomekl River, BC,
      Canada). This mixture contained organochlorine, organophosphorus, phenylurea, and
      triazine classes of pesticides. Fish given a realistic mixture exposure (total
      concentration, 1.01 ug/L) had increased plasma cortisol concentration, packed red
      cell volume, hematocrit (Hct), as well as decreased white cell volume, leukocrit
      (Lct). Similar changes in Hct and Lct were apparent after exposure to a lower
      concentration (0.186 ug/L). Interestingly, no changes in plasma cortisol
      concentration, Hct, or Lct were noted after exposure to a higher concentration
      (13.9 ug/L). This suggests that the exposure likely impaired the mechanisms
      enabling the stress response. Across all exposures, plasma glucose concentration
      was related to plasma cortisol concentration, not to pesticide mixture
      concentration. This suggests that a secondary stress response may be more related
      to variability in individual primary stress response than to differences in
      pesticide exposure concentrations. In summary, the present study indicates that
      salmon living in agrichemical-contaminated waterways may be experiencing stress,
      and this may pose a threat to their survival.

PMID- 21898557
TI  - Uptake and toxicity of spiked nickel to earthworm Eisenia fetida in a range of
      Chinese soils.
AB  - Bioavailability and toxicity of metals to soil organisms varies among different
      soils, and knowledge of this variance is useful for the development of soil
      environmental quality guidelines. In the present study, laboratory experiments
      were performed to investigate the effects of variations in nickel (Ni) uptake and
      toxicity on growth, cocoon output, and juvenile production in the earthworm
      Eisenia fetida in 13 Chinese soils spiked with nickel chloride. Body weight
      development of E. fetida was rather insensitive to Ni, and significant inhibition
      of growth was observed only at high Ni concentrations, such as 560 and 1000
      mg/kg. The 50% inhibition effect concentrations (EC50s) for cocoon and juvenile
      production, based on measured Ni concentrations in soils, varied from 169 to 684
      mg/kg and from 159 to 350 mg/kg, respectively. The EC50s represented
      approximately fourfold variation for cocoon output and twofold variation for
      juvenile production among 13 Chinese soils. Juvenile production, compared to
      cocoon output, was a more sensitive endpoint parameter to Ni. Nickel uptake in E.
      fetida increased as simple linear functions of increasing soil Ni concentrations.
      Tissue Ni-based EC50s (based on Ni concentrations in earthworm tissues) for
      cocoon production varied from 37 to 121 mg/kg (threefold variation) in 12 of 13
      soils, suggesting a similar variation to that of soil Ni-based EC50s.
      Relationship analysis between soil properties and Ni toxicity showed that neither
      the EC50s for cocoon output nor those for juvenile production presented
      significant correlation with soil properties (pH, organic matter content, cation
      exchange capacity, clay content, Ca2+ and Mg2+). This may be ascribed to the
      narrow range of properties of selected soils. The soil factors that determined Ni
      toxicity to earthworm reproduction remain undetermined in the present study, and
      these data should be used cautiously when developing toxicity prediction models
      because of the narrow selection of soil properties.

PMID- 21898558
TI  - Can avoidance behavior of the mite Oppia nitens be used as a rapid toxicity test
      for soils contaminated with metals or organic chemicals?
AB  - Survival and reproduction soil toxicity tests for a new mite test species, Oppia
      nitens, have recently been developed for boreal ecosystems; however, the tests
      require 28 to 35 d. Avoidance tests have the potential to allow for rapid
      preliminary screening assessments of soils. The objective of this investigation
      was to determine the relevance of the avoidance test with the oribatid mite O.
      nitens as a short screening test in lower-tier environmental risk assessment. We
      assessed the effects of soil properties and chemicals on O. nitens avoidance
      behavior as well as the minimum time required to obtain a significant avoidance
      response from the mite. Specimens of this mite were exposed in Organisation for
      Economic Co-Operation and Development (OECD) artificial soils that had been
      adjusted to achieve varying soil properties as well as to a range of
      concentrations of the following contaminants: Cu, Zn, Cd, Pb, phenanthrene,
      benzo[a]pyrene, geraniol, and boric acid over 1, 2, or 5 d. The results were then
      compared with those of parallel life-cycle toxicity studies. The results showed
      that 24 h was adequate to obtain a significant response of the mites and that the
      soil properties tested (moisture, pH, organic matter, and clay content) had
      little influence on mite avoidance. The median effective concentration (EC50) for
      avoidance response was lower than or in the same range as the reproduction EC50
      values for the organic compounds (phenanthrene and geraniol) and metals (Cu and
      Zn) or the median lethal concentration (LC50) values for Pb. The 24-h mite
      avoidance test is a suitable screening method across a range of soil properties
      and chemicals.

PMID- 21898559
TI  - Nutrient loss with runoff from fairway turf: an evaluation of core cultivation
      practices and their environmental impact.
AB  - The presence of excess nutrients in surface waters can result in undesirable
      environmental and economic consequences, including nuisance algal blooms and
      eutrophication. Fertilizer use in highly managed turf systems has raised
      questions concerning the contribution of nutrients to surrounding surface waters.
      Experiments were designed to quantify phosphorus and nitrogen transport with
      runoff from turf plots maintained as a golf course fairway to identify which
      cultural practice, solid tine (ST) or hollow tine (HT) core cultivation,
      maximized phosphorus and nitrogen retention at the site of fertilizer
      application. Simulated precipitation and collection of resulting runoff were
      completed 26 +/- 13 h following granular fertilizer application (18-3-18: N-P2O5
      K2O) and 63 d and 2 d following core cultivation. Runoff volumes were reduced in
      fairway turf plots aerated with HT relative to ST (63 d: 10%, 2 d: 55%
      reduction). Analysis of the runoff revealed a reduction in soluble phosphorus,
      ammonium nitrogen, and nitrate nitrogen losses with runoff from plots managed
      with HT; a 5 to 27% reduction after 63 d; and a 39 to 77% reduction at 2 d. Golf
      course runoff-to-surface water scenarios were used to calculate estimated
      environmental concentrations (EECs) of nitrogen and phosphorus in surface water
      receiving runoff from turf managed with ST or HT core cultivation. Surface water
      concentrations of phosphorus remained above the U.S. Environmental Protection
      Agency's water quality criteria to limit eutrophication, with the exception of
      concentrations associated with HT core cultivation at 2 d. Regardless of
      management practice (ST or HT) and time between core cultivation and runoff (63 d
      or 2 d), all EECs of nitrogen were below levels associated with increased algal
      growth. Understanding nutrient transport with runoff and identifying strategies
      that reduce off-site transport will increase their effectiveness at intended
      sites of application and minimize undesirable effects to surrounding surface
      water resources.

PMID- 21898560
TI  - Vitellogenin induction by 17beta-estradiol and 17alpha-ethynylestradiol in male
      Murray rainbowfish (Melanotaenia fluviatilis).
AB  - Hepatic vitellogenin (VTG) mRNA and plasma protein assays were developed for the
      Murray rainbowfish (Melanotaenia fluviatilis), a native freshwater fish species
      in Australia. Adult male Murray rainbowfish were exposed to 17beta-estradiol (E2)
      or 17alpha-ethynylestradiol (EE2) at 0, 1, 5, 10, 50, or 100 ng/L in a semistatic
      system for 7 d. Vitellogenin mRNA was quantified by quantitative polymerase chain
      reaction, and VTG protein was semiquantified in plasma using an enzyme-linked
      immunosorbent assay. Water concentrations were quantified by liquid
      chromatography coupled with tandem mass spectrometry and were on average 110% and
      85% nominal concentrations for E2 and EE2, respectively. Vitellogenin transcripts
      and protein were upregulated in male Murray rainbowfish exposed to either E2 or
      EE2 in a dose-responsive manner, with calculated 10% effective concentration
      (EC10) values for E2 of 3.71 ng/L and 11.6 ng/L for VTG mRNA and protein,
      respectively, and for EE2 of 2.77 ng/L and 8.47 ng/L for VTG mRNA and protein,
      respectively. Comparisons of these responses with responses of commonly used test
      species, including zebrafish (Danio rerio), fathead minnow (Pimephales promelas),
      and Japanese medaka (Oryzias latipes), revealed the Murray rainbowfish to be a
      sensitive test species for estrogenic effects via the estrogen receptor pathway.
      The present study suggests that the Murray rainbowfish would be a suitable
      candidate for future field studies designed for assessing estrogenic effects of
      effluent discharges in the Australian freshwater environment.

PMID- 21898561
TI  - Comparison of element concentrations in fir and rhododendron leaves and twigs
      along an altitudinal gradient.
AB  - Concentrations of 23 elements (Ca, K, Mg, P, Al, Cu, Fe, Mn, Mo, Na, Ni, Zn, Ag,
      Ba, Be, Cd, Co, Cr, Pb, Sb, Th, Tl, and V) in leaf and twig samples of a fir
      (Abies fabri) and a rhododendron (Rhododendron williamsianum) collected along an
      altitudinal gradient on Mount Gongga, China, are reported in the present study.
      Most of the macronutrients (K and P), micronutrients (Fe, Zn, Cu, Na, Ni, Mo, and
      Al), and trace elements (Pb, Tl, Ag, Cd, Ba, Co, V, Be, and Cr) are significantly
      enriched in fir when compared to rhododendron; however, Ca, Mg, Mn, Ba, and Cd
      are more enriched in rhododendron than in fir. Most of the elements in both
      plants are more significantly enriched in twigs than in leaves. The relationship
      between element concentration in plants and altitudinal gradient is nonlinear.
      Altitudes of 3,200 and 3,400 m are turning points for fir and rhododendron
      growth, respectively. Concentrations of all trace elements in the two plants
      along the altitudinal gradient are well below the toxic level in plants. No known
      industrial sources of the elements investigated exist in the Mount Gongga area,
      China. Element concentrations in the present study are higher than those found in
      mosses collected from the same area, indicating that the area is not
      contaminated. The element concentrations that we observed in plant samples were
      due to soil uptake. The pronounced differences between the two species are due to
      the different uptake characteristics of fir and rhododendron.

PMID- 21898562
TI  - Flesh residue concentrations of organochlorine pesticides in farmed and wild
      salmon from British Columbia, Canada.
AB  - The present study reports measured levels of organochlorine pesticides (OCPs) in
      commercial salmon feed (n = 8) and farmed Atlantic, coho, and chinook salmon (n =
      110), as well as wild coho, chinook, chum, sockeye, and pink salmon (n = 91).
      Flesh residue concentrations (ng/g wet weight) of
      dichlorodiphenyltrichloroethanes (DDTs), hexachlorocyclohexanes (HCHs),
      chlordanes, chlorobenzenes (CBz) and cyclodiene pesticides (e.g., dieldrin,
      mirex) were 2 to 11 times higher (p < 0.05) in farmed salmon compared with wild
      salmon. Concentrations were positively correlated with flesh lipid levels. Farmed
      Atlantic salmon (12-15% lipid) typically exhibited the greatest OCP burdens
      compared with other salmon species. However, when expressed on a lipid weight
      basis, concentrations of OCPs (ng/g lipid weight) in wild salmon, in many cases,
      exceeded those levels in farmed salmon. Observed interspecies and site-specific
      variations of OCP concentrations in farmed and wild salmon may be attributed to
      divergent life history, prey/feed characteristics and composition, bioenergetics,
      or ambient environmental concentrations. Calculated biomagnification factors (BMF
      = C(F)/C(D), lipid wt) of OCPs in farmed salmon typically ranged between two and
      five. Biomagnification of chemicals such as DDTs, chlordanes, and mirex was
      anticipated, because those compounds tend to exhibit high dietary uptake and slow
      depuration rates in fish because of relatively high octanol-water partition
      coefficients (K(OW)s > 105). Surprisingly, less hydrophobic pesticides such as
      hexachlorocyclohexanes and endosulfans (K(OW) s < 105) consistently exhibited a
      high degree of biomagnification in farmed salmon species (BMFs > 5). This is
      contrary to previous laboratory and field observations demonstrating fish BMFs
      less than 1 for low K(OW) chemicals, because of efficient respiratory elimination
      of those compounds via gills. The results suggest that ambient seawater
      concentrations and bioconcentration-driven accumulation may play a key role in
      the bioaccumulation of these relatively more water-soluble contaminants in farmed
      salmon. Finally, OCP exposure through consumption of British Columbian salmon is
      found to be low relative to United States national average per capita total
      exposure levels and provisional tolerable daily intakes.

PMID- 21898563
TI  - Bioaccumulation dynamics and exposure routes of Cd and Cu among species of
      aquatic mayflies.
AB  - Consumption of periphyton is a potentially important route of metal exposure to
      benthic invertebrate grazers. The present study examined the bioaccumulation
      kinetics of dissolved and dietary Cd and Cu in five species of mayflies (class
      Insecta). Artificial stream water and benthic diatoms were separately labeled
      with enriched stable metal isotopes to determine physiological rate constants
      used by a biokinetic bioaccumulation model. The model was employed to simulate
      the effects of metal partitioning between water and food, expressed as the
      bioconcentration factor (BCF), as well as ingestion rate (IR) and metal
      assimilation efficiency of food (AE), on the relative importance of water and
      food to metal bioaccumulation. For all test species, the contribution of dietary
      uptake of Cd and Cu increased with BCF. For a given BCF, the contribution of food
      to the body burden increased with k(uf) , the metal uptake rate constant from
      food that combined variation in IR and AE. To explore the relative importance of
      water and diet exposure routes under field conditions, we used estimated site
      specific aqueous free-ion concentrations to model Cd and Cu accumulation from
      aqueous exposure, exclusively. The predicted concentrations accounted for less
      than 5% of the observed concentrations, implying that most bioaccumulated metal
      was acquired from food. At least for the taxa considered in this study, we
      conclude that consumption of metal-contaminated periphyton can result in elevated
      metal body burdens and potentially increase the risk of metal toxicity.

PMID- 21898564
TI  - Legacy and contemporary persistent organic pollutants in North Pacific albatross.
AB  - Here we report the first measurements of polybrominated diphenyl ethers (PBDE 47,
      99, and 153) alongside 11 organochlorine pesticides (OCPs) and 28 polychlorinated
      biphenyls (PCBs) in the plasma of albatross from breeding colonies distributed
      across a large spatial east-west gradient in the North Pacific Ocean. North
      Pacific albatross are wide-ranging, top-level consumers that forage in pelagic
      regions of the North Pacific Ocean, making them an ideal sentinel species for
      detection and distribution of marine contaminants. Our work on contaminant
      burdens in albatross tissue provides information on transport of persistent
      organic pollutants (POPs) to the remote North Pacific and serves as a proxy for
      regional environmental quality. We sampled black-footed (Phoebastria nigripes; n
      = 20) and Laysan albatross (P. immutabilis; n = 19) nesting on Tern Island,
      Hawaii, USA, and Laysan albatross (n = 16) nesting on Guadalupe Island, Mexico.
      Our results indicate that North Pacific albatross are highly exposed to both PCBs
      and OCPs, with levels ranging from 8.8 to 86.9 ng/ml wet weight and 7.4 to 162.3
      ng/ml wet weight, respectively. A strong significant gradient exists between
      Laysan albatross breeding in the Eastern Pacific, having approximately 1.5-fold
      and 2.5-fold higher levels for PCBs and OCPs, respectively, compared to those
      from the Central Pacific. Interspecies levels of contaminants within the same
      breeding site also showed high variation, with Tern black-footed albatross having
      approximately threefold higher levels of both PCBs and OCPs than Tern Laysan
      albatross. Surprisingly, while PBDEs are known to travel long distances and
      bioaccumulate in wildlife of high trophic status, we detected these three PBDE
      congeners only at trace levels ranging from not detectable (ND) to 0.74 ng/ml wet
      weight in these albatross.

PMID- 21898565
TI  - Quantification of perchloroethylene residues in dry-cleaned fabrics.
AB  - We have used a novel gas chromatography/mass spectrometry (GC/MS)-based approach
      to quantify perchloroethylene (PCE) residues in dry-cleaned fabrics. Residual PCE
      was extracted from fabric samples with methanol and concentration was calculated
      by the gas chromatographic peak area, standardized using PCE calibration data.
      Extracts examined were from samples of 100% wool, polyester, cotton, or silk,
      which were dry cleaned from one to six times in seven different Northern Virginia
      dry-cleaning establishments. Additional experiments were conducted to investigate
      the kinetics of PCE release in the extraction solvent and to the open air. We
      found that polyester, cotton, and wool retained >= uM levels of PCE, that these
      levels increased in successive dry-cleaning cycles, and that PCE is slowly
      volatilized from these fabrics under ambient room air conditions. We found that
      silk does not retain appreciable PCE. Measured differences across dry-cleaning
      establishments and fabric type suggest more vigorous monitoring of PCE residues
      may be warranted. Environ. Toxicol. Chem. 2011;30:2481-2487. (c) 2011 SETAC.

PMID- 21898566
TI  - Biodegradation of triclosan in biosolids-amended soils.
AB  - Land application of biosolids can constitute an important source of triclosan
      (TCS) input to soils, with uncertain effects. Several studies have investigated
      the degradation potential of TCS in biosolids-amended soils, but the results vary
      widely. We conducted a laboratory degradation study by mixing biosolids spiked
      with [14C]-TCS (final concentration = 40 mg/kg) with Immokalee fine sand and
      Ashkum silty clay loam soils at an agronomic application rate (22 Mg/ha).
      Biosolids-amended soils were aerobically incubated in biotic and inhibited
      conditions for 18 weeks. Subsamples removed at 0, 2, 4, 6, 9, 12, 15, and 18
      weeks were sequentially extracted with an operationally defined extraction scheme
      to determine labile and nonlabile TCS fractions. Over the 18-week incubation, the
      proportion of [14C] in the nonlabile fraction increased and the labile fraction
      decreased, suggesting decreasing availability to biota. Partitioning of TCS into
      labile and nonlabile fractions depended on soil characteristics. Less than 0.5%
      of [14C]-TCS was mineralized to carbon dioxide (14CO2) in both soils and all
      treatments. A degradation metabolite, methyl triclosan (Me-TCS), was identified
      in both soils only in the biotic treatment, and increased in concentration over
      time. Even under biotic conditions, biosolids-borne TCS is persistent, with a
      primary degradation (TCS to Me-TCS) half-life of 78 d in the silty clay loam and
      421 d in the fine sand. A half-life of approximately 100 d would be a
      conservative first approximation of TCS half-life in biosolids-amended soils for
      risk estimation.

PMID- 21898567
TI  - Comparative toxicity of two glyphosate formulations (original formulation of
      Roundup(r) and Roundup WeatherMAX(r)) to six North American larval anurans.
AB  - The toxicity of two glyphosate formulations (the original formulation of
      Roundup(r) and Roundup WeatherMAX(r)) to six species of North American larval
      anurans was evaluated by using 96-h static, nonrenewal aqueous exposures. The 96
      h median lethal concentration values (LC50) ranged from 1.80 to 4.22 mg acid
      equivalent (ae)/L and 1.96 to 3.26 mg ae/L for the original formulation of
      Roundup and Roundup WeatherMAX, respectively. Judged by LC50 values, four species
      were more sensitive to Roundup WeatherMAX exposures, and two species were more
      sensitive to the original formulation. Two of six species, Bufo fowleri (p <
      0.05, F = 14.89, degrees of freedom [df] = 1) and Rana clamitans (p < 0.05, F =
      18.46, df = 1), had significantly different responses to the two formulations
      tested. Increased sensitivity to Roundup WeatherMAX likely was due to differences
      in the surfactants or relative amounts of the surfactants in the two
      formulations. Potency slopes for exposures of the original formulation ranged
      from 24.3 to 92.5% mortality/mg ae/L. Thresholds ranged from 1.31 to 3.68 mg
      ae/L, showing an approximately three times difference in the initiation of
      response among species tested. For exposures of Roundup WeatherMAX, slopes ranged
      from 49.3 to 84.2% mortality/mg ae/L. Thresholds ranged from 0.83 to 2.68 mg
      ae/L. Margins of safety derived from a simulated direct overspray were above 1,
      except for one species in exposures of Roundup WeatherMAX. Laboratory data based
      on aqueous exposures are conservative because of the lack of environmental
      ligands; however, these tests provide information regarding the relative toxicity
      between these two Roundup formulations.

PMID- 21898568
TI  - Current-use pesticide transport to Costa Rica's high-altitude tropical cloud
      forest.
AB  - To gain insight into the atmospheric transport and deposition of organic
      contaminants in high-altitude forests in the humid tropics, pesticides were
      analyzed in air, water, and soil samples from Costa Rica. Passive samplers
      deployed across the country revealed annually averaged air concentrations of
      chlorothalonil, endosulfan, and pendimethalin that were higher in areas with
      intensive agricultural activities than in more remote areas. Atmospheric
      concentrations were particularly high in the intensively cultivated central
      valley. Only endosulfan and its degradation products were found in soils sampled
      along an altitudinal transect on the northern side of Volcano Turrialba, which is
      facing heavily cultivated coastal plains. Consistent with calculations of cold
      trapping in tropical mountains, concentrations of endosulfan sulfate increased
      with altitude. Pesticide levels in lake, creek, fog, and arboreal water samples
      from high-elevation cloud forests were generally below 10 ng . L(-1). Endosulfan
      sulfate was the most abundant pesticide in water, with concentrations ranging
      from 0.4 to 9.4 ng . L(-1). Its levels were highest in water sampled from
      bromeliads. Levels of total endosulfan in water are much lower than the reported
      median lethal concentration (LC50) value for acute toxicity of alpha-endosulfan
      to tadpoles. Although this suggests that the presence of pesticide might not have
      a direct impact on amphibian populations, the possibility of effects of chronic
      exposure to a mixture of substances cannot be excluded. Fog was relatively
      enriched in some of the analyzed pesticides, such as dacthal and chlorothalonil,
      and may constitute an important deposition pathway to high-altitude tropical
      cloud forest.

PMID- 21898569
TI  - Improved understanding of tributyltin sorption on natural and biochar-amended
      sediments.
AB  - A poor understanding of tributyltin (TBT) sorption on sediments has hindered an
      accurate evaluation of its environmental fate. The present study determined TBT
      sorption by a freshwater sediment (BH) and a coastal marine sediment (TZ) as
      influenced by pH, salinity, and biochar (BC) amendment into TZ. The isotherms
      were essentially linear, with K(OC) values in the range of 10(4) to 10(5) L/kg.
      Tributyltin sorption at pH 3.56 and 8.00 occurred mainly via partitioning. It
      reached maxima at pH equal to its pK(a) (=6.25) because of added ion exchange. A
      salinity increase from 5 to 35 practical salinity units enhanced TBT sorption at
      pH 3.56 and 8.00 on TZ by approximately 30% and on BH by approximately 80%,
      ascribed to the salting-out effect that reduced the solubilities of tributyltin
      hydroxide (TBTOH) and tributyltin chloride (TBTCl). At pH 6.25, the same salinity
      increase reduced TBT sorption on TZ by approximately 20% but enhanced TBT
      sorption on BH by approximately 35%. This was attributed to the enhancing role of
      salting out and the reducing role of metal competition for ion exchange.
      Tributyltin was two orders of magnitude more effectively sorbed by BC than by
      total organic carbon of TZ, mainly because of the high level of surface area of
      the BC. Although BC affinity for TBT may be significantly diminished when present
      in TZ, it was considered to be the primary contributor to TBT sorption from
      water. Biochar may thus be used to immobilize TBT in sediment for potential
      remediation.

PMID- 21898570
TI  - Review of the reproductive biology of amphipods and their endocrine regulation:
      identification of mechanistic pathways for reproductive toxicants.
AB  - The reproductive biology of amphipods is reviewed to update the knowledge of the
      male and female reproductive processes of oogenesis and spermatogenesis as well
      as the endocrine systems of amphipods with the aim of advancing studies of
      reproductive toxicology. The ovarian and reproduction cycles of female
      gammaridean amphipods are closely correlated with the molt cycle, which is under
      direct control by the steroid hormone 20-hydroxyecdysone. The ability of males to
      copulate and subsequently for females to ovulate is restricted to the early
      postmolt period of the females. New developments in our understanding of the molt
      cycle and the endocrine regulatory pathways for reproduction using genomics
      techniques on other crustacean species are also discussed. The arthropod sterol
      ponasterone A or xenobiotics such as the fungicide fenarimol have been shown to
      elicit endocrine disruption in some crustaceans by acting as an agonist for 20
      hydroxyecdysone at the ecdysone receptor or by inhibiting the synthesis of 20
      hydroxyecdysone, respectively, resulting in disruption of molting and
      reproduction. Recent studies suggest that cadmium can inhibit secondary
      vitellogenesis in amphipods. Experimental approaches for examining the metabolic
      pathways associated with ecdysteroid hormonal signaling or metabolism,
      exoskeleton maintenance and molting, and the regulation of vitellogenin in
      amphipods are discussed. This information should aid in the identification of
      useful biomarkers for reproductive toxicity.

PMID- 21898571
TI  - Therapeutic apheresis before and after kidney transplantation.
AB  - Kidney transplantation is considered the treatment of choice for most individuals
      with end-stage kidney disease, as well as the most cost-effective renal
      replacement therapy for the health care system that serves them. Immunologic
      sensitization, defined by the presence of antibodies directed against foreign HLA
      (or so called, donor specific antibodies, or DSA), is a significant barrier to
      kidney transplantation. Further, the presence of DSA is associated with an
      increase in the incidence of antibody-mediated rejection and decreased graft
      survival following transplantation. Therapeutic plasma exchange, an
      extracorporeal therapy directed at removing plasma proteins, including DSA, has
      proven to be an important part of a comprehensive strategy to minimize the effect
      of sensitization before, and following kidney transplantation. As such, it offers
      the promise of increasing access to transplantation, as well as improving
      outcomes following transplantation. In this concise narrative review, we describe
      more specifically the benefits of kidney transplantation, the epidemiology of
      kidney transplantation in the United States, the clinical significance of anti
      HLA antibodies, and the evidence supporting a role for therapeutic plasma
      exchange before and after kidney transplantation.

PMID- 21898572
TI  - Extracorporeal photopheresis: how, when, and why.
AB  - Extracorporeal photopheresis (ECP) is a well-tolerated procedure that suppresses
      T-lymphocyte activity in a clonally-specific way. It is an effective therapy that
      has established indications in the management of cutaneous T-cell lymphoma, graft
      versus-host disease and some scenarios of solid-organ transplant rejection. It is
      being used increasingly around the world. Its applications are evolving,
      including exploration of its potential for treating autoimmune diseases where
      cytotoxic T-cell-mediated mechanisms appear to be involved, such as Crohn's
      disease. This article reviews scientific insights into its mechanism of action on
      the immune system, details of the clinical procedure, its clinical applications
      in various diseases, and the current evidence for its efficacy and place in
      medical therapeutics.

PMID- 21898573
TI  - Therapeutic apheresis: a review of complications and recommendations for
      prevention and management.
AB  - Therapeutic apheresis procedures are a form of extracorporeal therapy that use
      different techniques to separate blood into the different components out of which
      the part containing the etiological agent in a disease process is discarded and
      the rest of the components of blood are re-infused into the patient, frequently
      with the addition of a replacement fluid or volume. These complex procedures have
      inherent risks of adverse events and factors that may impact on the incidence
      these events include the underlying disease state, anticoagulation techniques,
      replacement fluid type including the volume, issues related to the vascular
      access used, and the therapeutic apheresis procedure type and technique. We
      present a representative case based review of common complications of therapeutic
      apheresis and suggestions about how to prevent or manage these as presented at
      the 2010 Therapeutic Apheresis Academy.

PMID- 21898574
TI  - Selected questions and answers given by apheresis medicine experts at TAA 2010.

PMID- 21898575
TI  - The potential role of plasma exchange as a treatment for bilateral diffuse uveal
      melanocytic proliferation: a report of two cases.
AB  - Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare
      paraneoplastic syndrome associated with gynecologic malignancies in women and
      pancreatic or lung carcinomas in men. The clinical presentation consists of the
      rapid onset of decreased visual acuity due to bilateral serous retinal detachment
      and cataracts. Pathologically, there is diffuse uveal thickening and
      proliferation of uveal melanocytes. The onset of blindness is often rapid, with
      some patients presenting with blindness. We describe the cases of two women with
      gynecologic malignancies who were treated with plasma exchange (PE) for BDUMP.
      After a course of five to seven procedures, their ocular disease stabilized. One
      patient has maintained her vision more than 1 year following the completion of
      the course of PE. The other patient, who also received treatment with
      corticosteroids, in addition to the PE, reported stable vision on telephone
      follow-up 9 months after presentation. These cases suggest that PE may be a
      treatment option in this rare paraneoplastic syndrome which has otherwise been
      reported to invariably result in vision loss.

PMID- 21898576
TI  - Therapeutic plasma exchange for the treatment of anti-NMDA receptor encephalitis.
AB  - Anti-N-methyl-D-aspartate receptor (NMDA-R) encephalitis is thought to be one of
      the common paraneoplastic-associated encephalitides. Between February 2001 and
      February 2011, nine patients were diagnosed with this disorder at Columbia
      University Medical Center: eight females (mean age 23 years) and one male (3
      years of age). Four female patients had ovarian teratomas, which were removed as
      part of their treatment. Therapeutic plasma exchange (TPE) was used as one of the
      treatment modalities in addition to immunosuppressive therapy, including
      corticosteroids, intravenous immunoglobulin (IVIG), and/or rituximab. A total of
      56 TPE procedures were performed in these patients on alternate days (range, 5-14
      procedures/patient). Approximately 1 plasma volume (PV) was processed for all
      patients; 5% albumin and 0.9% normal saline were used as replacement fluid.
      Complications occurred in 20% of TPE procedures; 9% were possibly due to
      underlying disease. The remaining 11% of complications were hypotensive episodes
      that rapidly responded to either a fluid bolus or a vasopressor treatment. One
      patient demonstrated immediate clinical improvement after three TPE treatments,
      and four patients had significant improvement at time of discharge from the
      hospital. Long-term follow-up showed that early initiation of TPE appears to be
      beneficial, and patients who received IVIG after TPE did better than those who
      received IVIG before TPE. However, the number of patients in this series is too
      small to provide statistically significant conclusions. Overall, TPE is a
      relatively safe treatment option in patients with anti-NMDA-R encephalitis.
      Further studies are needed to elucidate the benefit of TPE in this disease.

PMID- 21898577
TI  - A suite of microsatellite markers optimized for amplification of DNA from Addax
      (Addax nasomaculatus) blood preserved on FTA cards.
AB  - The addax (Addax nasomaculatus) is a critically endangered antelope that is
      currently maintained in zoos through regional, conservation breeding programs. As
      for many captive species, incomplete pedigree data currently impedes the ability
      of addax breeding programs to confidently manage the genetics of captive
      populations and to select appropriate animals for reintroduction. Molecular
      markers are often used to improve pedigree resolution, thereby improving the long
      term effectiveness of genetic management. When developing a suite of molecular
      markers, it is important to consider the source of DNA, as the utility of markers
      may vary across DNA sources. In this study, we optimized a suite of
      microsatellite markers for use in genotyping captive addax blood samples
      collected on FTA cards. We amplified 66 microsatellite loci previously described
      in other Artiodactyls. Sixteen markers amplified a single product in addax, but
      only 5 of these were found to be polymorphic in a sample of 37 addax sampled from
      a captive herd at Fossil Rim Wildlife Center in the US. The suite of
      microsatellite markers developed in this study provides a new tool for the
      genetic management of captive addax, and demonstrates that FTA cards can be a
      useful means of sample storage, provided appropriate loci are used in downstream
      analyses.

PMID- 21898578
TI  - Violence risk assessment and women: predictive accuracy of the HCR-20 in a civil
      psychiatric sample.
AB  - Research to date has not adequately demonstrated whether the HCR-20 Violence Risk
      Assessment Scheme (HCR-20; Webster, Douglas, Eaves, & Hart, 1997), a structured
      violence risk assessment measure with a robust literature supporting its validity
      in male samples, is a valid indicator of violence risk in women. This study
      utilized data from the MacArthur Study of Mental Disorder and Violence to
      retrospectively score an abbreviated version of HCR-20 in 827 civil psychiatric
      patients. HCR-20 scores and predictive accuracy of community violence were
      compared for men and women. Results suggested that the HCR-20 is slightly, but
      not significantly, better for evaluating future risk for violence in men than in
      women, although the magnitude of the gender differences was small and was largely
      limited to historical factors. The results do not indicate that the HCR-20 needs
      to be tailored for use in women or that it should not be used in women, but they
      do highlight that the HCR-20 should be used cautiously and with full awareness of
      its potential limitations in women.

PMID- 21898579
TI  - A longitudinal examination of sex offender recidivism prior to and following the
      implementation of SORN.
AB  - The goals of the present study were to examine the recidivism rates of two
      matched samples of sexual offenders, those released prior to and after sex
      offender registration and notification (SORN) in New Jersey. The pre-SORN group
      (1990-1994) included 247 offenders, while the post-SORN group (1996-2000)
      included 248 offenders. The longitudinal analysis demonstrated that for sex
      offenders released from prison both prior to and after implementation of SORN,
      there are clearly two distinguishable groups of sex offenders in relation to
      patterns of recidivism. More than three-quarters of sex offenders were identified
      as at low risk of recidivism, with low rates of repeat criminal offenses. By
      contrast, the high-risk group of offenders was not only more likely to commit
      future criminal offenses, including sex offenses, but they were also more likely
      to commit significantly more offenses and to do so fairly quickly following
      release. Analyses also include an examination of the influence of demographics,
      substance abuse and mental health issues, treatment history, sex offense incident
      characteristics, and criminal history on recidivism. Finally, SORN status was not
      a significant predictor of sex or general recidivism. The study limitations and
      policy implications are discussed.

PMID- 21898580
TI  - Biomechanical and histological analysis after tenotomy of the long head of the
      biceps in the rabbit shoulder model.
AB  - Tenotomy of the long head of the biceps tendon (LHBT) is gaining popularity in
      shoulder surgery. We evaluated biomechanical and histological changes after
      tenotomy in a rabbit LHBT tenotomy model to confirm that autotenodesis is a
      phenomenon that occurs after the procedure. Twenty-three rabbits were included.
      The right shoulder was harvested from 10 randomly selected rabbits. The shoulders
      were tested to determine the pullout strength of LHBT at the bicipital groove
      immediately after being tenotomized. The left shoulder of three of these rabbits
      also underwent histological analysis. The other 13 rabbits underwent LHBT
      tenotomy (tenotomy model). Six weeks post-operatively, 10 were assigned for
      biomechanical study, and three underwent histological analysis. The pullout
      strength and histology were compared with the immediate post-tenotomy data. The
      pullout strength of the immediate post-tenotomy (5.53 +/- 2.22 N) was
      significantly (p < 0.001) less than the pullout strength of the 6 weeks post
      tenotomy model (44.07 +/- 7.75 N). On histological analysis, marked fibrosis was
      noted around the LHBT at the bicipital groove in the 6 weeks post-tenotomy model.
      Adhesion of the LHBT at the bicipital groove after tenotomy, which is called
      "autotenodesis," is a definite phenomenon that could help the tendon resist
      distal migration of the LHBT after tenotomy. These results support execution of
      biceps tenotomy in shoulder surgery.

PMID- 21898581
TI  - The response of the rabbit subsynovial connective tissue to a stress-relaxation
      test.
AB  - The subsynovial connective tissue (SSCT) in the carpal tunnel may play a role in
      the etiology of carpal tunnel syndrome (CTS), yet the material properties of the
      SSCT remain unclear. Thus, we investigated the mechanical response of the SSCT in
      a rabbit model. Twenty-four rabbit cadaver paws were used for mechanical testing;
      two paws were used for scanning electron microscopy (SEM) imaging. After testing
      normal tendon excursion, the divided third digit flexor digitorum superficialis
      (FDS) tendon was pulled to displacements of 2, 3.5, 5, or 8 mm, maintained at
      that position until force decay, and then the process was repeated. Normal
      excursion of the FDS averaged 4.8 mm. The ratio of the second peak force to the
      first peak force in the 2 mm group was 0.98 (SD = 0.16), which was significantly
      higher than the other groups (3.5 mm: 0.74, 5 mm, 0.63, and 8 mm: 0.59; p <
      0.05). SEM showed ruptured fibrils in the displaced specimen. The declining force
      ratio with displacements >2 mm suggests damage to the SSCT within the
      physiological tendon excursion. These data may be useful in understanding SSCT
      mechanics in CTS, which is associated with SSCT fibrosis.

PMID- 21898582
TI  - Investigations of the origin of phase differences seen with ultrashort TE imaging
      of short T2 meniscal tissue.
AB  - Ultrashort echo time MRI requires specialized pulse sequences with nominal echo
      times as low as a few microseconds to detect signals from the short T(2) tissues
      frequently encountered in the musculoskeletal system. Usually, magnitude images
      are reconstructed and these often show low tissue contrast. Ultrashort echo time
      phase images of the meniscus show surprisingly high contrast despite their very
      short echo time. In this article, we investigated the source of this contrast
      using the Bloch equations, simulations, phantom experiments, and tissue studies.
      Phase evolution was shown to occur in ultrashort echo time sequences during the
      finite radiofrequency pulse and readout periods, and previously unrecognized
      susceptibility differences between fiber groups were observed in the meniscus.

PMID- 21898583
TI  - Interaction of hydrated protons with octyl-phenyl-N,N-diisobutylcarbamoylmethyl
      phosphine oxide (CMPO): NMR and theoretical study.
AB  - Interaction of octyl-phenyl-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO,
      the 'classical' rare metal extraction agent) with fully ionized hydrated protons
      (HP) was studied in acetonitrile-d(3) using (1)H, (13)C, (31)P NMR, PFG NMR and
      magnetic relaxation. The experimental results were confronted with high-precision
      ab initio DFT calculations. Relative chemical shifts of NMR signals of CMPO (0.01
      mol/L) under the presence of HP in the molar ratio beta = 0-2.0 mol/mol show
      binding between CMPO and HP. Self-diffusion measurements using (1)H PFG NMR
      demonstrate that larger complexes with higher content of CMPO are generally
      formed at beta < 0.75. Analyzing the collective dependence of (13)C and (31)P NMR
      chemical shifts on beta by the use of program LETAGROP, we obtained very good
      fitting for the assumed coexistence of two complexes (CMPO)(2).HP (C(2)) and
      CMPO.HP (C(1)). The logarithms of the respective stabilization constants log K(i)
      were found to be 7.518 (C(2)) and 4.581 (C(1)). The system dynamics was studied
      by measuring the transverse (1)H NMR relaxation using CPMG sequence with varying
      delays t(p) between the pi pulses in the mixtures with beta = 0.4-0.8. The
      following exchange correlation times were obtained: tau(10) = 2.35 * 10(-5),
      tau(20) = 0.82 * 10(-4), tau(21) = 0.45 * 10(-3) s. The DFT calculations support
      the conclusion that the complexes C(1) and C(2) are the main species in the
      mixtures of CMPO with HP. They also agree with the NMR and FTIR observation that
      the main site to which H(3) O(+) is bound is the P=O group, whereas the amide
      group does not form a strong bond with the ion when excess water molecules are
      present.

PMID- 21898584
TI  - Magnetic resonance analysis of capillary formation reaction front dynamics in
      alginate gels.
AB  - The formation of heterogeneous structures in biopolymer gels is of current
      interest for biomedical applications and is of fundamental interest to
      understanding the molecular level origins of structures generated from disordered
      solutions by reactions. The cation-mediated physical gelation of alginate by
      calcium and copper is analyzed using magnetic resonance measurements of spatially
      resolved molecular dynamics during gel front propagation. Relaxation time and
      pulse-field gradient methods are applied to determine the impact of ion front
      motion on molecular translational dynamics. The formation of capillaries in
      alginate copper gels is correlated to changes in translational dynamics.

PMID- 21898585
TI  - Alkaloids from Hippeastrum morelianum Lem. (Amaryllidaceae).
AB  - The Amaryllidaceae family has proven to be a rich source of active molecules. As
      part of an ongoing project, we report a phytochemical study of Hippeastrum
      morelianum (Amaryllidaceae), from which we have isolated two homolycorine-type
      alkaloids, the new 2alpha,7-dimethoxyhomolycorine (1) and the poorly described
      candimine (2), as well as six known alkaloids: tazettine, pretazettine, 3
      epimacronine, haemanthamine, hamayne and trisphaeridine. For reference purposes,
      the NMR of the isolated compounds was unequivocally described, based on 2D NMR
      measurements including (1)H-(1)H COSY, (1)H-(1)H NOESY, HSQC and HMBC.

PMID- 21898586
TI  - Structure elucidation of two new unusual monoterpene glycosides from Euphorbia
      decipiens, by 1D and 2D NMR experiments.
AB  - Two new unusual monoterpene glycosides, (Z)-3,6-dimethyl-3-(beta-D-O
      glucosylmethylene)cyclohept-4-ene-1-one (1) and 3,6-dimethyl-3-(beta-D-O
      glucosylmethylene)cycloheptanone (2) have been isolated along with five known
      compounds, 3-hydroxy-4-methoxybenzoic acid, 6,7-dihydroxycoumarin, luteolin,
      apigenin 5-O-alphal-L-rhamnoside, and pinocembrin-7-O-rutinoside from ethyl
      acetate extract of Euphorbia decipiens. The structures of the isolated compounds
      were elucidated by extensive 1D- and 2D-NMR, and mass spectroscopic analyses.

PMID- 21898587
TI  - Formyl migration product of chanoclavine-I aldehyde in the presence of the old
      yellow enzyme FgaOx3 from Aspergillus fumigatus: a NMR structure elucidation.
AB  - A previous study showed that together with the festuclavine synthase FgaFS, the
      old yellow enzyme FgaOx3 from Aspergillus fumigatus catalyzed the conversion of
      chanoclavine-I aldehyde to festuclavine in the biosynthesis of ergot alkaloids.
      In the absence of FgaFS, a mixture containing two compounds with a ratio of 7:3
      was detected in the enzyme assay of FgaOx3. NMR experiments including (DQF)-COSY,
      HSQC, HMBC and NOESY identified their structures as E/Z isomers of N-methyl-N
      [(5R,10R)-10-(2-oxo-propyl)-2,4,5,10-tetrahydrobenzo[cd]indol-5-yl]formamide and
      proved the migration of the formyl group at C-8 in chanoclavine I-aldehyde to N-6
      in the identified products.

PMID- 21898588
TI  - Lineage-committed osteoclast precursors circulate in blood and settle down into
      bone.
AB  - Osteoclasts are derived from the monocyte/macrophage lineage, but little is known
      about osteoclast precursors in circulation. We previously showed that cell cycle
      arrested quiescent osteoclast precursors (QOPs) were detected along bone surfaces
      as direct osteoclast precursors. Here we show that receptor activator of NF
      kappaB (RANK)-positive cells isolated from bone marrow and peripheral blood
      possess characteristics of QOPs in mice. RANK-positive cells expressed c-Fms
      (receptors of macrophage colony-stimulating factor) at various levels, but
      scarcely expressed other monocyte/granulocyte markers. RANK-positive cells failed
      to exert phagocytic and proliferating activities, and differentiated into
      osteoclasts but not into dendritic cells. To identify circulating QOPs, collagen
      disks containing bone morphogenetic protein-2 (BMP disks) were implanted into
      mice, which were administered bromodeoxyuridine daily. Most nuclei of osteoclasts
      detected in BMP-2-induced ectopic bone were bromodeoxyuridine-negative. RANK
      positive cells in peripheral blood proliferated more slowly and had a much longer
      lifespan than F4/80 (a macrophage marker)-positive macrophages. When BMP disks
      and control disks were implanted in RANK ligand-deficient mice, RANK-positive
      cells were observed in the BMP disks but not in the controls. F4/80-positive
      cells were distributed in both disks. Administration of FYT720, a sphingosine 1
      phosphate agonist, promoted the egress of RANK-positive cells from hematopoietic
      tissues into bloodstream. These results suggest that lineage-determined QOPs
      circulate in the blood and settle in the bone.

PMID- 21898589
TI  - Heterogeneity of fracture pathogenesis in urban South African children: the birth
      to twenty cohort.
AB  - South African black children fracture less than white children. Differences in
      bone mass, body composition, and physical activity may be contributing risk
      factors. This study aimed to investigate the association between fracture
      prevalence, bone mass, and physical activity in South African children. Using the
      Bone Health cohort of the Birth to Twenty longitudinal study, we retrospectively
      obtained information of lifetime fractures until age 15 years in 533 subjects.
      Whole-body bone mineral content (BMC), bone area (BA), fat mass (FM), and lean
      mass (LM) (measured by dual-energy X-ray absorptiometry [DXA]), anthropometric
      data, physical activity scores, and skeletal maturity were obtained at ages 10
      and 15 years. Nonfracturing black females were used as the control group and
      comparisons were made between those who did and did not fracture within the same
      sex and ethnic groups. Of the 533 subjects, 130 (24%) reported a fracture (black,
      15%; white, 41.5%; p  <  0.001). White males who fractured were significantly
      taller (10 years, p  <  0.01), more physically active (15 years, p  <  0.05) and
      had higher LM (10 years, p  =  0.01; 15 years, p  <  0.001), whereas white
      females who fractured were fatter (10 and 15 years, p  =  0.05 and p  <  0.05,
      respectively), than their nonfracturing peers. White males who fractured had
      greater BA and BMC at all sites at 10 and 15 years compared to their
      nonfracturing peers after adjusting for differences in height and weight; BA and
      BMC were similar in each of the other sex and ethnic groups. No anthropometric or
      bone mass differences were found between black children with and without
      fractures. The factor associated with fractures in white males appears to be
      participation in sports activities, while in white females obesity appears to
      play a role. No contributing factors in black males and females were found, and
      needs further elucidation.

PMID- 21898590
TI  - Denosumab and changes in bone turnover markers during androgen deprivation
      therapy for prostate cancer.
AB  - Androgen deprivation therapy (ADT) for prostate cancer increases fracture risk,
      decreases bone mineral density, and increases bone turnover markers (BTMs)
      including serum type 1 C-telopeptide (sCTX), tartrate-resistant alkaline
      phosphatase 5b (TRAP-5b), and procollagen-1 N-terminal telopeptide (P1NP). In a
      prespecified exploratory analysis of a phase 3, multicenter, double-blind study,
      we evaluated the effects of denosumab (60 mg subcutaneously every 6 months for 3
      years) versus placebo (1468 patients, 734 in each group) on BTM values. BTMs were
      measured at baseline, month 1, and predose at months 6, 12, 24, and 36 in the
      overall population. BTMs at month 1 are also reported for subgroups based on age
      (<  70 years versus >=  70 years), prior duration of ADT (<=  6 months versus > 6
      months), and baseline BTM (<=  median versus >  median BTM values). Treatment
      with denosumab provided a rapid and sustained decrease of BTM values compared
      with placebo. The median change in sCTX levels at month 1 was -90% in the
      denosumab group and -3% in the placebo group (p  <  0.0001). The median change in
      TRAP-5b levels at month 1 was -55% in the denosumab group and -3% in the placebo
      group (p <  0.0001). The maximal median change in P1NP was -64% in the denosumab
      group and -11% in the placebo group, (p  <  0.0001). Significantly greater
      decreases in BTM for denosumab were also seen in subgroup analyses based on age,
      prior ADT treatment, and baseline BTM values. Suppression of bone turnover
      markers was consistent with marked increases in bone mineral density reported
      previously.

PMID- 21898591
TI  - 1,25-dihydroxyvitamin D3 influences cellular homocysteine levels in murine
      preosteoblastic MC3T3-E1 cells by direct regulation of cystathionine beta
      synthase.
AB  - High homocysteine (HCY) levels are a risk factor for osteoporotic fracture.
      Furthermore, bone quality and strength are compromised by elevated HCY owing to
      its negative impact on collagen maturation. HCY is cleared by cystathionine beta
      synthase (CBS), the first enzyme in the transsulfuration pathway. CBS converts
      HCY to cystathionine, thereby committing it to cysteine synthesis. A microarray
      experiment on MC3T3-E1 murine preosteoblasts treated with 1,25-dihydroxyvitamin
      D(3) [1,25(OH)(2) D(3) ] revealed a cluster of genes including the cbs gene, of
      which the transcription was rapidly and strongly induced by 1,25(OH)(2) D(3) .
      Quantitative real-time PCR and Western blot analysis confirmed higher levels of
      cbs mRNA and protein after 1,25(OH)(2) D(3) treatment in murine and human cells.
      Moreover, measurement of CBS enzyme activity and quantitative measurements of
      HCY, cystathionine, and cysteine concentrations were consistent with elevated
      transsulfuration activity in 1,25(OH)(2) D(3) -treated cells. The importance of a
      functional vitamin D receptor (VDR) for transcriptional regulation of cbs was
      shown in primary murine VDR knockout osteoblasts, in which upregulation of cbs in
      response to 1,25(OH)(2) D(3) was abolished. Chromatin immunoprecipitation on chip
      and transfection studies revealed a functional vitamin D response element in the
      second intron of cbs. To further explore the potential clinical relevance of our
      ex vivo findings, human data from the Longitudinal Aging Study Amsterdam
      suggested a correlation between vitamin D status [25(OH)D(3) levels] and HCY
      levels. In conclusion, this study showed that cbs is a primary 1,25(OH)(2) D(3)
      target gene which renders HCY metabolism responsive to 1,25(OH)(2) D(3).

PMID- 21898593
TI  - Crucial role of the cryptic epitope SLAYGLR within osteopontin in renal crystal
      formation of mice.
AB  - Osteopontin plays a crucial role in the formation of renal calcium crystals,
      which are primarily induced by renal tubular cell injury, especially
      mitochondrial damage. We have previously shown that the impaired Arg-Gly-Asp
      (RGD) sequence of osteopontin inhibits renal crystal formation by using OPN
      transgenic mice and OPN-knockout (OPN-KO) mice. Here, we investigated the effects
      of an antimurine osteopontin antibody (35B6-Ab) that specifically reacts with the
      (162) SLAYGLR(168) sequence, which is exposed by thrombin cleavage and is located
      adjacent to the RGD sequence, on renal crystal formation. Renal crystals induced
      by daily administration of glyoxylate over 9 days (from days 1 to 9) in a murine
      model were sporadically detected in the renal tubular cells at the
      corticomedullary junction, where thrombin-cleaved osteopontin expression was also
      coincidentally detected. On days 0, 3, 6, and 9, 35B6-Ab administration inhibited
      renal crystal formation and induced significant morphological changes in a dose
      dependent manner (250, 500, and 1000 ug per mouse). Scanning electron microscopy
      showed that the crystals in 35B6-Ab-treated mice were aberrantly formed and their
      density was low; in contrast, the crystals in untreated mice that were not
      administered 35B6-Ab had a radial pattern of growth (rosette petal-like
      crystals), and their density was high. Microstructure analysis of renal tubular
      cells by transmission electron microscopy revealed that untreated mice showed
      collapsed mitochondria in the flattened cytoplasm of renal tubular cells, unlike
      the corresponding structures in 35B6-Ab-treated mice, in which renal tubular cell
      injury was inhibited. In vitro, 35B6-Ab was found to inhibit the attachment of
      (14) C-labeled crystals to renal tubular culture cells and reduce morphological
      damage to these cells. We conclude that thrombin-cleaved osteopontin plays an
      important role in formation of renal calcium crystals and that 35B6-Ab
      contributes to the remarkable inhibition of early-stage renal crystal formation
      by preventing renal tubular cell injury and crystal-cell attachment.

PMID- 21898592
TI  - Ubiquitination-deubiquitination balance dictates ligand-stimulated PTHR sorting.
AB  - Parathyroid hormone receptors (PTHR) are promptly internalized upon stimulation
      by activating (PTH[1-84], PTH[1-34]) and non-activating (PTH[7-84], PTH[7-34])
      ligands. Here, we characterized the mechanism regulating the sorting of
      internalized receptors between recycling and degradative pathways. PTHR recycles
      faster after challenge with PTH(1-34) than with PTH(7-34). PTHR recycling is
      complete by 2 h after PTH(1-34) stimulation, but incomplete at this time in cells
      treated with PTH(7-34). The slower and incomplete recycling induced by PTH(7-34)
      is due to proteasomal degradation. Both PTH(1-34) and PTH(7-34) induced PTHR
      polyubiquitination. Ubiquitination by PTH(1-34) was transient, whereas receptor
      ubiquitination after PTH(7-34) was sustained. PTH(1-34), but not PTH(7-34),
      induced expression of the PTHR-specific deubiquitinating enzyme USP2.
      Overexpression of USP2 prevented PTH(7-34)-induced PTHR degradation. We conclude
      that PTH(1-34) promotes coupled PTHR ubiquitination and deubiquitination, whereas
      PTH(7-34) activates only ubiquitination, thereby leading to PTHR downregulation.
      These findings may explain PTH resistance in diseases associated with elevated
      PTH(7-84) levels.

PMID- 21898594
TI  - Breastfeeding protects against hip fracture in postmenopausal women: the Tromso
      study.
AB  - Despite reported bone loss during pregnancy and lactation, no study has shown
      deleterious long-term effects of parity or breastfeeding. Studies have shown
      higher bone mineral density and reduced risk for fracture in parous than in
      nulliparous women or no effect of parity and breastfeeding, so long-term effects
      are uncertain. We studied the effect of parity and breastfeeding on risk for hip,
      wrist and non-vertebral fragility fractures (hip, wrist, or proximal humerus) in
      4681 postmenopausal women aged 50 to 94 years in the Tromso Study from 1994-95 to
      2010, using Cox's proportional hazard models. During 51 906 person-years, and a
      median of 14.5 years follow-up, 442, 621, and 1105 of 4681 women suffered
      incident hip, wrist, and fragility fractures, and the fracture rates were 7.8,
      11.4, and 21.3 per 1000 person-years, respectively. The risk for hip, wrist, and
      fragility fracture did not differ between parous (n = 4230, 90.4%) and
      nulliparous women (n = 451, 9.6%). Compared with women who did not breast-feed
      after birth (n = 184, 4.9%), those who breastfed (n = 3564, 95.1%) had 50% lower
      risk for hip fracture (HR 0.50; 95% CI 0.32 to 0.78), and 27% lower risk for
      fragility fracture (HR 0.73; 95% CI 0.54 to 0.99), but similar risk for wrist
      fracture, after adjustment for age, BMI, height, physical activity, smoking, a
      history of diabetes, previous fracture of hip or wrist, use of hormone
      replacement therapy, and length of education. Each 10 months longer total
      duration of breastfeeding reduced the age-adjusted risk for hip fracture by 12%
      (HR 0.88; 95% CI 0.78 to 0.99, p for trend = 0.03) before, and marginally after,
      adjustment for BMI and other covariates (HR 0.91; 95% CI 0.80 to 1.04). In
      conclusion, this data indicates that pregnancy and breastfeeding has no long-term
      deleterious effect on bone fragility and fractures, and that breastfeeding may
      contribute to a reduced risk for hip fracture after menopause.

PMID- 21898595
TI  - Biological constraints that limit compensation of a common skeletal trait variant
      lead to inequivalence of tibial function among healthy young adults.
AB  - Having a better understanding of how complex systems like bone compensate for the
      natural variation in bone width to establish mechanical function will benefit
      efforts to identify traits contributing to fracture risk. Using a collection of
      pQCT images of the tibial diaphysis from 696 young adult women and men, we tested
      the hypothesis that bone cells cannot surmount the nonlinear relationship between
      bone width and whole bone stiffness to establish functional equivalence across a
      healthy population. Intrinsic cellular constraints limited the degree of
      compensation, leading to functional inequivalence relative to robustness, with
      slender tibias being as much as two to three times less stiff relative to body
      size compared with robust tibias. Using Path Analysis, we identified a network of
      compensatory trait interactions that explained 79% of the variation in whole-bone
      bending stiffness. Although slender tibias had significantly less cortical area
      relative to body size compared with robust tibias, it was the limited range in
      tissue modulus that was largely responsible for the functional inequivalence.
      Bone cells coordinately modulated mineralization as well as the cortical porosity
      associated with internal bone multicellular units (BMU)-based remodeling to
      adjust tissue modulus to compensate for robustness. Although anecdotal evidence
      suggests that functional inequivalence is tolerated under normal loading
      conditions, our concern is that the functional deficit of slender tibias may
      contribute to fracture susceptibility under extreme loading conditions, such as
      intense exercise during military training or falls in the elderly. Thus, we show
      the natural variation in bone robustness was associated with predictable
      functional deficits that were attributable to cellular constraints limiting the
      amount of compensation permissible in human long bone. Whether these cellular
      constraints can be circumvented prophylactically to better equilibrate function
      among individuals remains to be determined.

PMID- 21898596
TI  - The Wilson films--bilateral postural tremor.

PMID- 21898597
TI  - The interplay of cholinergic function, attention, and falls in Parkinson's
      disease.
AB  - Dopamine loss in the substantia nigra causes several of the motor signs seen in
      Parkinson's disease, but there is now increasing evidence highlighting the
      importance of cholinergic loss in the pathophysiology of nonmotor symptoms. The
      nucleus basalis of Meynert supplies the majority of the cholinergic input to the
      cerebral cortex, with the pedunculopontine nucleus providing many subcortical
      structures with acetylcholine. Both these structures undergo degeneration in
      Parkinson's disease (PD), with more severe loss associated with cognitive
      impairment. The risk of dementia in PD is greater than that in control subjects,
      with impairments in attention, visuospatial function, and executive control
      dominating. Imaging studies have demonstrated degeneration of the cholinergic
      system in PD, Parkinson's disease dementia, and dementia with Lewy bodies, with
      improvements in attention seen following the introduction of cholinesterase
      inhibitors. Conversely, anticholinergic drugs are associated with cognitive
      decline, with neuropathology studies indicating the presence of increased
      neurofibrillary tangles and senile plaque formation. In addition, these drugs are
      also known to precipitate visual hallucinations, lending support to a cholinergic
      basis for visual hallucinations in PD. Gait, falls, and cognition may also be
      related, as evidenced by the findings that fallers perform less well on test of
      attention than nonfallers and that greater postural instability is associated
      with worse scores on attention and executive function. It is therefore feasible
      that cognition (namely, attention), visual hallucinations, falls, and gait are
      subserved by acetylcholine, and this is further explored in this clinically
      orientated review.

PMID- 21898598
TI  - Childhood treatment with psychotropic medication and development of comorbid
      medical conditions in adolescent-onset bipolar disorder.
AB  - OBJECTIVE: This study aims to investigate the association between early treatment
      with psychotropic medications and the development of medical comorbidities in
      pediatric patients who develop bipolar disorder (BD). METHODS: Data from the
      South Carolina Medicaid program covering all medical services and medication
      prescriptions between January 1996 and December 2005 were used to determine the
      association between childhood exposure to psychotropic medications (i.e.,
      psychostimulants, antidepressants, and antipsychotics) and the diagnosis of
      select comorbid medical conditions in 1841 children and adolescents diagnosed
      with Diagnostic and Statistical Manual IV defined BD. RESULTS: In separate
      regressions controlling for all psychotropic medications prescribed and all
      comorbid medical conditions diagnosed prior to the BD, hypertension and
      cardiovascular disorders were more likely in those prescribed second generation
      antipsychotics or psychostimulants, whereas obesity/overweight was more likely in
      those taking serotonin norepinephrine reuptake inhibitor/heterocyclic
      antidepressants, and asthma was more likely in those taking selective serotonin
      reuptake inhibitors. CONCLUSION: Childhood cardiometabolic events appear to be
      systematically associated with specific classes of psychotropic medications, but
      no innate, developmental sequencing of cardiometabolic abnormalities was apparent
      before early adolescence in patients subsequently diagnosed and treated for BD.

PMID- 21898599
TI  - The relationships of 'ecstasy' (MDMA) and cannabis use to impaired executive
      inhibition and access to semantic long-term memory.
AB  - This study aimed to examine the relationship between the consumption of ecstasy
      (3,4-methylenedioxymethamphetamine (MDMA)) and cannabis, and performance on the
      random letter generation task which generates dependent variables drawing upon
      executive inhibition and access to semantic long-term memory (LTM). The
      participant group was a between-participant independent variable with users of
      both ecstasy and cannabis (E/C group, n = 15), users of cannabis but not ecstasy
      (CA group, n = 13) and controls with no exposure to these drugs (CO group, n =
      12). Dependent variables measured violations of randomness: number of repeat
      sequences, number of alphabetical sequences (both drawing upon inhibition) and
      redundancy (drawing upon access to semantic LTM). E/C participants showed
      significantly higher redundancy than CO participants but did not differ from CA
      participants. There were no significant effects for the other dependent
      variables. A regression model comprising intelligence measures and estimates of
      ecstasy and cannabis consumption predicted redundancy scores, but only cannabis
      consumption contributed significantly to this prediction. Impaired access to
      semantic LTM may be related to cannabis consumption, although the involvement of
      ecstasy and other stimulant drugs cannot be excluded here. Executive inhibitory
      functioning, as measured by the random letter generation task, is unrelated to
      ecstasy and cannabis consumption.

PMID- 21898600
TI  - Posttraumatic stress hyperarousal symptoms mediate the relationship between
      childhood exposure to violence and subsequent alcohol misuse in Mi'kmaq youth.
AB  - This study was part of a school-based collaborative research project with a
      Canadian Mi'kmaq community that examined the potential role of posttraumatic
      stress (PTS) symptom clusters in mediating the relationship between childhood
      exposure to violence (EV) and alcohol misuse in a sample of Mi'kmaq adolescents
      (N = 166). The study employed a cross-sectional design and used several well
      validated self-report questionnaires. Path analytic results showed that when each
      PTS symptom cluster was independently investigated for mediating effects while
      controlling for depressive symptoms, age, and gender, only the PTS hyperarousal
      symptom cluster fully mediated the EV-alcohol misuse relationship. Results are
      discussed within the context of previous theory and research on the topic of PTS
      as a mediator between EV and alcohol misuse.

PMID- 21898601
TI  - Sleep fears, sleep disturbance, and PTSD symptoms in minority youth exposed to
      Hurricane Katrina.
AB  - Posttraumatic stress disorder (PTSD) is common following the experience of a
      natural disaster and sleep disturbance is an important influence on its course in
      adults, but little research is available examining sleep and PTSD in youths. This
      study's objective was to evaluate the role of sleep disturbance and the
      developmentally influenced factor of fear of sleeping alone in the maintenance of
      posttraumatic stress (PTS) symptoms in youths. Deidentified data of 191 Hurricane
      Katrina survivors ages 8 to 15 were used in this study. We found cross-sectional
      relationships of sleep disturbance and fear of sleeping alone with PTS symptom
      severity. Longitudinal analysis also indicated that general sleep disturbance at
      24 months (T1) was predictive of PTS symptoms severity at 30 months (T2) even
      after adjusting for PTS symptom severity at T1, age, sex, and continued disrepair
      to the home. These results have implications for intervention strategies among
      youth exposed to traumatic events.

PMID- 21898603
TI  - A resilience-oriented treatment for posttraumatic stress disorder: results of a
      preliminary randomized clinical trial.
AB  - This preliminary randomized trial examined the effect of a resilience-oriented
      intervention for posttraumatic stress disorder (PTSD) versus a waitlist control
      on anxiety and depressive symptoms, positive emotional health, and cognitive
      performance in 39 veterans with a variety of traumatic exposures. From pre- to
      posttreatment, the intervention but not the control group showed improvements
      that were large in magnitude for affective symptoms and positive emotional health
      (ds = 0.73-1.18), moderate in magnitude for memory (ds = 0.50-0.54), and small-to
      moderate in magnitude for executive function (ds = 0.30-0.35). Findings suggest
      that treatment explicitly targeting resilience resources (e.g., positive
      emotional engagement, social connectedness) may provide broad benefits, including
      alleviation of anxiety and depressive symptoms and improved positive emotional
      and cognitive function.

PMID- 21898602
TI  - Peritraumatic and trait dissociation differentiate police officers with resilient
      versus symptomatic trajectories of posttraumatic stress symptoms.
AB  - Research has consistently demonstrated that stress reactions to potentially
      traumatic events do not represent a unified phenomenon. Instead, individuals tend
      to cluster into prototypical response patterns over time including chronic
      symptoms, recovery, and resilience. We examined heterogeneity in a posttraumatic
      stress disorder (PTSD) symptom course in a sample of 178 active-duty police
      officers following exposure to a life-threatening event using latent growth
      mixture modeling (LGMM). This analysis revealed 3 discrete PTSD symptom
      trajectories: resilient (88%), distressed-improving (10%), and distressed
      worsening (2%). We further examined whether trait and peritraumatic dissociation
      distinguished these symptom trajectories. Findings indicate that trait and
      peritraumatic dissociation differentiated the resilient from the distressed
      improving trajectory (trait, p < .05; peritraumatic, p < .001), but only
      peritraumatic dissociation differentiated the resilient from the distressed
      worsening trajectory (p < .001). It is essential to explore heterogeneity in
      symptom course and its predictors among active-duty police officers, a repeatedly
      exposed group. These findings suggest that police officers may be a highly
      resilient group overall. Furthermore, though there is abundant evidence that
      dissociation has a positive linear relationship with PTSD symptoms, this study
      demonstrates that degree of dissociation can distinguish between resilient and
      symptomatic groups of individuals.

PMID- 21898604
TI  - Motor nerve lengths of twenty-seven muscles in upper extremity.
AB  - The purpose of this study is to determine the lengths of motor nerves in the
      upper extremity. Motor nerves of 27 muscles in 10 cadavers (16 extremities) were
      dissected from their roots at the level of intervertebral foramen to the entry
      point of the nerves to the corresponding muscles. Distance between acromion and
      the lateral epicondyle of the humerus was also measured in all cadavers. Nerve
      length of the coracobrachialis muscle was the shortest (18.26 +/- 1.64 cm), while
      the longest was the nerve of the extensor indicis (59.51 +/- 4.80 cm). The biceps
      brachii, the extensor digitorum communis, and the brachialis muscles showed
      highest coefficient of variation that makes these nerve lengths of muscles
      inconsistent about their lengths. This study also offers quotients using division
      of the lengths of each nerve to acromion-the lateral epicondyle distance.
      Knowledge of the nerve lengths in the upper extremity may provide a better
      understanding the reinnervation sequence and the recovery time in the multilevel
      injuries such as brachial plexus lesions. Quotients may be used to estimate
      average lengths of nerves of upper extremity in infants and children. Moreover,
      reliability of the biceps brachii as a determinant factor for surgery in
      obstetrical brachial plexus lesions should be reconsidered due to its highest
      variation coefficient.

PMID- 21898605
TI  - Electrical and mechanical anharmonicities from NIR-VCD spectra of compounds
      exhibiting axial and planar chirality: the cases of (S)-2,3-pentadiene and methyl
      d(3) (R)- and (S)-[2.2]paracyclophane-4-carboxylate.
AB  - The IR and Near infrared (NIR) vibrational circular dichroism (VCD) spectra of
      molecules endowed with noncentral chirality have been investigated. Data for
      fundamental, first, and second overtone regions of (S)-2,3-pentadiene, exhibiting
      axial chirality, and methyl-d(3) (R)- and (S)-[2.2]paracyclophane-4-carboxylate,
      exhibiting planar chirality have been measured and analyzed. The analysis of NIR
      and IR VCD spectra was based on the local-mode model and the use of density
      functional theory (DFT), providing mechanical and electrical anharmonic terms for
      all CH-bonds. The comparison of experimental and calculated spectra is
      satisfactory and allows one to monitor fine details in the asymmetric charge
      distribution in the molecules: these details consist in the harmonic frequencies,
      in the principal anharmonicity constants, in both the atomic polar and axial
      tensors and in their first and second derivatives with respect to the CH
      stretching coordinates.

PMID- 21898606
TI  - Choline-derivate-modified nanoparticles for brain-targeting gene delivery.

PMID- 21898607
TI  - Novel benzo[1,2-b:4,5-b']dithiophene-benzothiadiazole derivatives with variable
      side chains for high-performance solar cells.

PMID- 21898609
TI  - Complementary metal oxide semiconductor technology with and on paper.

PMID- 21898608
TI  - Hydride formation in single palladium and magnesium nanoparticles studied by
      nanoplasmonic dark-field scattering spectroscopy.

PMID- 21898610
TI  - Stereoselective and diversity-oriented synthesis of trisubstituted allylic
      alcohols and amines.
AB  - Stereoselective and diversity-oriented synthesis of trisubstituted olefins was
      achieved by using ortho-diphenylphosphanyl benzoate (o-DPPB) as a directing group
      for allylic substitution. The starting point of this methodology was a set of
      alpha-methylene aldehydes derived from Baylis-Hillman adducts. Subsequent
      addition of different organometallic reagents led to a variety of allylic alcohol
      substrates. After introduction of the reagent-directing o-DPPB group, copper
      mediated allylic substitution with a wide range of Grignard reagents enabled the
      stereoselective construction of a large number of E-configured trisubstituted
      allylic alcohols and amines in excellent yields and stereoselectivities.
      Remarkable is the synthetic flexibility, which allows a wide range of
      permutations starting from an aldehyde followed by successive introduction of the
      substituents R(2) and R(3) from organometallic Grignard based reagents. Thus,
      starting from only a few precursors, a diversity-oriented synthesis of
      stereodefined trisubstituted allylic alcohols and amines becomes possible.

PMID- 21898611
TI  - Bond stretching and redox behavior in coinage metal complexes of the
      dichalcogenide dianions [(SPh2P)2CEEC(PPh2S)2]2- (E=S, Se): diradical character
      of the dinuclear copper(I) complex (E=S).
AB  - The metathetical reactions of a) [Li(tmeda)](2)[(S)C(PPh(2)S)(2)] (Li(2).3c) with
      CuCl(2) and b) [Li(tmeda)](2)[(SPh(2)P)(2)CSSC(PPh(2)S)(2)] (Li(2).4c) with two
      equivalents of CuCl both afford the binuclear Cu(I) complex
      {Cu(2)[(SPh(2)P)(2)CSSC(PPh(2)S)(2)]} (5c). The elongated (C)S-S(C) bond (ca.
      2.54 and 2.72 A) of the dianionic ligand observed in the solid-state structure of
      5c indicate the presence of diradical character as supported by theoretical
      analyses. The treatment of [Li(tmeda)](2)[(SPh(2)P)(2)CSeSeC(PPh(2)S)(2)]
      (Li(2).4b) and Li(2).4c with AgOSO(2)CF(3) produce the analogous Ag(I)
      derivatives, {Ag(2)[(SPh(2)P)(2)CEEC(PPh(2)S)(2)]} (6b, E=Se; 6c, E=S),
      respectively. The diselenide complex 6b exhibits notably weaker Ag-Se(C) bonds
      than the corresponding contacts in the Cu(I) congeners, and the (31)P NMR data
      suggest a possible isomerization in solution. In contrast to the metathesis
      observed for Cu(I) and Ag(I) reagents, the reactions of Li(2).4b and Li(2).4c
      with Au(CO)Cl involve a redox process in which the dimeric dichalcogenide ligands
      are reduced to the corresponding monomeric dianions, [(E)C(PPh(2)S)(2)](2-) (3b,
      E=Se; 3c, E=S), and one of the gold centers is oxidized to generate the mixed
      valent Au(I)/Au(III) complexes, {Au[(E)C(PPh(2)S)(2)]}(2) (7b, E=Se; 7c, E=S),
      with relatively strong aurophilic Au(I)...Au(III) interactions. The new compounds
      5c, 6b,c and 7b,c are characterized in solution by NMR spectroscopy and in the
      solid state by X-ray crystallography (5c, 6b, 7b and 7c) and by Raman
      spectroscopy (5c and 6c). The UV-visible spectra of coinage metal complexes of
      the type 5, 6 and 7 are discussed in the light of results from theoretical
      analyses using time-dependent density functional theory.

PMID- 21898612
TI  - The "missing link": the gas-phase generation of platinum-methylidyne clusters
      Pt(n)CH+ (n=1, 2) and their reactions with hydrocarbons and ammonia.
AB  - Electrospray ionization (ESI) of tetrameric platinum(II) acetate,
      [Pt(4)(CH(3)COO)(8)], in methanol generates the formal platinum(III) dimeric
      cation [Pt(2)(CH(3)COO)(3)(CH(2)COO)(MeOH)(2)](+), which, upon harsher ionization
      conditions, sequentially loses the two methanol ligands, CO(2), and CH(2)COO to
      form the platinum(II) dimer [Pt(2)(CH(3)COO)(2)(CH(3))](+). Next, intramolecular
      sequential double hydrogen-atom transfer from the methyl group concomitant with
      the elimination of two acetic acid molecules produces Pt(2)CH(+) from which, upon
      even harsher conditions, PtCH(+) is eventually generated. This degradation
      sequence is supported by collision-induced dissociation (CID) experiments,
      extensive isotope-labeling studies, and DFT calculations. Both PtCH(+) and
      Pt(2)CH(+) react under thermal conditions with the hydrocarbons C(2)H(n) (n=2, 4,
      6) and C(3)H(n) (n=6, 8). While, in ion-molecule reactions of PtCH(+) with C(2)
      hydrocarbons, the relative rates decrease with increasing n, the opposite trend
      holds true for Pt(2)CH(+). The Pt(2)CH(+) cluster only sluggishly reacts with
      C(2)H(2), but with C(2)H(4) and C(2)H(6) dihydrogen loss dominates. The reactions
      with the latter two substrates were preceded by a complete exchange of all of the
      hydrogen atoms present in the adduct complex. The PtCH(+) ion is much less
      selective. In the reactions with C(2)H(2) and C(2)H(4), elimination of H(2)
      occurs; however, CH(4) formation prevails in the decomposition of the adduct
      complex that is formed with C(2)H(6). In the reaction with C(2)H(2), in addition
      to H(2) loss, C(3)H(3)(+) is produced, and this process formally corresponds to
      the transfer of the cationic methylidyne unit CH(+) to C(2)H(2), accompanied by
      the release of neutral Pt. In the ion-molecule reactions with the C(3)
      hydrocarbons C(3)H(6) and C(3)H(8), dihydrogen loss occurs with high selectivity
      for Pt(2)CH(+), but in the reactions of these substrates with PtCH(+) several
      reaction routes compete. Finally, in the ion-molecule reactions with ammonia,
      both platinum complexes give rise to proton transfer to produce NH(4)(+);
      however, only the encounter complex generated with PtCH(+) undergoes efficient
      dehydrogenation of the substrate, and the rather minor formation of CNH(4)(+)
      indicates that C-N bond coupling is inefficient.

PMID- 21898613
TI  - On the determination of the stereochemistry of semisynthetic natural product
      analogues using chiroptical spectroscopy: desulfurization of
      epidithiodioxopiperazine fungal metabolites.
AB  - Isolation and semisynthetic modification of the fungal metabolite chaetocin gave
      access to a desulfurized analogue of this natural product. Detailed chiroptical
      studies, comparing experimentally obtained optical rotation values, electronic
      circular dichroism spectra, and vibrational circular dichroism spectra to
      computationally simulated ones, reveal the desulfurization of chaetocin to
      unambiguously proceed with retention of configuration. Consideration of the
      plausible mechanisms for this process highlighted inconsistencies in the
      stereochemical assignment of related molecules in the literature. This in turn
      allowed the stereochemical reassignment of the natural product analogue
      dethiodehydrogliotoxin.

PMID- 21898614
TI  - Photoinduced multielectron transfer to a multicopper oxidase resulting in
      dioxygen reduction into water.

PMID- 21898615
TI  - Modifying cage structures in metal-organic polyhedral frameworks for H2 storage.
AB  - Three isostructural metal-organic polyhedral cage based frameworks (denoted NOTT
      113, NOTT-114 and NOTT-115) with (3,24)-connected topology have been synthesised
      by combining hexacarboxylate isophthalate linkers with {Cu(2)(RCOO)(4)}
      paddlewheels. All three frameworks have the same cuboctahedral cage structure
      constructed from 24 isophthalates from the ligands and 12 {Cu(2)(RCOO)(4)}
      paddlewheel moieties. The frameworks differ only in the functionality of the
      central core of the hexacarboxylate ligands with trimethylphenyl, phenylamine and
      triphenylamine moieties in NOTT-113, NOTT-114 and NOTT-115, respectively.
      Exchange of pore solvent with acetone followed by heating affords the
      corresponding desolvated framework materials, which show high BET surface areas
      of 2970, 3424 and 3394 m(2) g(-1) for NOTT-113, NOTT-114 and NOTT-115,
      respectively. Desolvated NOTT-113 and NOTT-114 show high total H(2) adsorption
      capacities of 6.7 and 6.8 wt%, respectively, at 77 K and 60 bar. Desolvated NOTT
      115 has a significantly higher total H(2) uptake of 7.5 wt% under the same
      conditions. Analysis of the heats of adsorption (Q(st)) for H(2) reveals that
      with a triphenylamine moiety in the cage wall, desolvated NOTT-115 shows the
      highest value of Q(st) for these three materials, indicating that
      functionalisation of the cage walls with more aromatic rings can enhance the
      H(2)/framework interactions. In contrast, measurement of Q(st) reveals that the
      amine-substituted trisalkynylbenzene core used in NOTT-114 gives a notably lower
      H(2)/framework binding energy.

PMID- 21898616
TI  - Facing the gem-dialkyl effect in enzyme inhibitor design: preparation of
      homocycloleucine-based azadipeptide nitriles.

PMID- 21898617
TI  - Near-infrared fluorescent nanoparticles formed by self-assembly of lipidic
      (Bodipy) dyes.

PMID- 21898618
TI  - Boron/nitrogen substitution of the central carbon atoms of the biphenalenyl
      diradical pi dimer: a novel 2e-12c bond and large NLO responses.
AB  - On the basis of the famous staggered biphenalenyl diradical pi dimer 1, the
      eclipsed biphenalenyl (1a), with no centrosymmetry, was obtained by rotating a
      layer of 1 by 60 degrees  around its central axis. Furthermore, the central
      carbon atoms of 1 and 1a were substituted by boron and nitrogen atoms to form 2
      and 2a with a novel 2e-12c bond. We found that the novel 2e-12c bond is formed by
      the electron pair of the occupied orbital of the phenalenyl monomer substituted
      by the nitrogen atom and the unoccupied orbital of the phenalenyl monomer
      substituted by the boron atom. As a result of the novel 2e-12c bond, 2 and 2a
      exhibit a fascinating interlayer charge-transfer transition character, which
      results in a significant difference in the dipole moments (DeltaMU) between the
      ground state and the crucial excited state. The values of DeltaMU for 2 and 2a
      are 6.4315 and 6.9253 Debye, clearly larger than the values of 0 and 0.0015 Debye
      for 1 and 1a. Significantly, the boron/nitrogen substitution effect can greatly
      enhance the first hyperpolarizabilities (beta(0) ) of 2 and 2a with a novel 2e
      12c bond compared with 1 and 1a with a traditional 2e-12c bond: 0 and 19 a.u. for
      1 and 1a are much lower than 3516 and 12272 a.u. for 2 and 2a. Furthermore, the
      interaction energies (E(int) )of 2 and 2a are larger than those of 1 and 1a,
      which could be considered as a signature of reliability for the newly designed
      dimers. Our present work will be beneficial for further theoretical and
      experimental studies on the properties of molecules with the novel 2e-12c bond.

PMID- 21898619
TI  - Persistent hydrogen-bonded and non-hydrogen-bonded phenoxyl radicals.
AB  - The production of stable phenoxyl radicals is undoubtedly a synthetic chemical
      challenge. Yet it is a useful way to gain information on the properties of the
      biological tyrosyl radicals. Recently, several persistent phenoxyl radicals have
      been reported, but only limited synthetic variations could be achieved. Herein,
      we show that the amide-o-substituted phenoxyl radical (i.e. with a salicylamide
      backbone) can be synthesised in a stable manner, thereby permitting easy
      synthetic modifications to be made through the amide bond. To study the effect of
      H-bonding on the properties of the phenolate/phenoxyl radical redox couple,
      simple H-bonded and non-H-bonded o,p-tBu-protected salicylamidate compounds have
      been prepared. Their redox properties were examined by cyclic voltammetry and
      showed a fully reversible one-electron oxidation process to the corresponding
      phenoxyl radical species. Remarkably, the redox potential appears to be
      correlated, at least partially, with H-bond strength, as relatively large
      differences (ca. 300 mV) in the redox potential between H-bonded and non-H-bonded
      phenolate salts are observed. The corresponding phenoxyl radicals produced
      electrochemically are persistent at room temperature for at least an hour; their
      UV/Vis and EPR characterisation is consistent with that of phenoxyl radicals,
      which makes them excellent models of biological tyrosyl radicals. The analyses of
      the experimental data coupled with theoretical calculations indicate that both
      the deviation from planarity of the amide function and intramolecular H-bonding
      influence the oxidation potential of the phenolate. The latter H-bonding effect
      appears to be predominantly exerted on the phenolate and not (or only a little)
      on the phenoxyl radical. Thus, in these systems the H-bonding energy involved in
      the phenoxyl radical appears to be relatively small.

PMID- 21898620
TI  - High-performance separation of fullerenes on metal-organic framework MIL-101(Cr).

PMID- 21898621
TI  - BINAP versus BINAP(O) in asymmetric intermolecular Mizoroki-Heck reactions:
      substantial effects on selectivities.
AB  - 2,2'-Bis(diphenylphosphino)-1,1'-binaphthyl (BINAP) was employed as chiral ligand
      in the enantioselective intermolecular Mizoroki-Heck reaction, whereas the use of
      cognate BINAP(O) (monooxidized BINAP) is unprecedented. The regio- and
      enantioselectivity of the arylation of representative cyclic alkenes changes
      dramatically in the presence of hemilabile BINAP(O) instead of BINAP. The
      arylation of 2,3-dihydrofuran is perfectly regiodivergent (98:2 versus 0:100) and
      the arylation of cyclopentene is only enantioselective with BINAP(O) [60 versus
      10% enantiomeric excess (ee)]. Use of [Pd(2)(dba)(3)]?dba
      (dba=dibenzylideneacetone) instead of Pd(OAc)(2) produces as high as 86% ee in
      the arylation of cyclopentene.

PMID- 21898622
TI  - In search of oligo(2-thienyl)-substituted pyridine derivatives: a modular
      approach to di-, tri- and tetra(2-thienyl)pyridines.
AB  - Herein, we describe our attempts to systematically prepare a series of oligo(2
      thienyl)-substituted pyridine derivatives. The crucial starting material, a beta
      alkoxy-beta-ketoenamide, is easily available on a large scale by the reaction of
      lithiated methoxyallene with thiophene-2-carbonitrile and thiophene-2-carboxylic
      acid. This three-component reaction is followed by intramolecular cyclization to
      yield the suitably functionalized 2,6-di(2-thienyl)-substituted pyridine
      derivates. The two oxygen atoms allow the programmed activation of positions C-3,
      C-4, or C-5 of the pyridine ring to perform palladium-catalyzed coupling
      reactions with thiophene-2-boronic acid or 2-(tributylstannyl)thiophene, and
      alternatively, reductive removal of groups. With this concept, we were able to
      prepare five pyridine derivatives with 2-thienyl substituents in the 2,6-, 2,3,6
      , 2,4,6-, 2,3,4,6-, and 2,3,5,6-positions. 2,3,4,5,6-Penta(2-thienyl)pyridine was
      not available with our methods. The UV/Vis and fluorescence spectra of all
      pyridines were recorded and showed a dependence on the substitution pattern and
      protonation state. For the protonated 2,3,5,6-tetra(2-thienyl)-substituted
      pyridine, a Stokes shift of about 180 nm with an emission at 515 nm was observed.

PMID- 21898623
TI  - Surface organobarium and organomagnesium chemistry on periodic mesoporous silica
      MCM-41: convergent and sequential approaches traced by molecular models.
AB  - The alkaline earth metal alkyl complexes [Ba(AlEt(4))(2)](n) and Mg(AlMe(4))(2)
      were directly grafted onto periodic mesoporous silica MCM-41, which had been
      dehydroxylated at 270  degrees C (specific surface area a(s): 1023 m(2) g(-1);
      pore volume V(p): 1.08 cm(3) g(-1); main pore diameter 3.4 nm). Alternatively,
      barium alkyl surface species were generated by sequential grafting of MCM-41 with
      Ba[N(SiHMe(2))(2)](2)(thf)(4) and AlEt(3) to yield the hybrid material
      AlEt(3)@Ba[N(SiHMe(2))(2)](2)(thf)(4)@MCM-41. For a better understanding of the
      surface chemistry, AlEt(3)@MCM-41 was also accessed. All hybrid materials were
      analyzed by diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy,
      elemental analysis, nitrogen physisorption, and solid-state NMR spectroscopy;
      this clearly revealed distinct surface chemistry for the alkylaluminate-treated
      materials [Ba(AlEt(4))(2)]@MCM-41 and Mg(AlMe(4))(2)@MCM-41. In an attempt to
      mimic the surface chemistry, the organometallic precursors were treated with
      HOSi(OtBu)(3). The reaction of equimolar amounts of {Ba[N(SiHMe(2))(2)](2)}(n)
      and HOSi(OtBu)(3) produced a mixed silylamido/siloxide cluster of
      Ba(3)[OSi(OtBu)(3)](3)[N(SiHMe(2))(2)](3) with bridging-only siloxide ligands as
      well as one bridging and two terminal silylamido ligands. The Schlenk equilibrium
      was found to govern the [Ba(AlEt(4))(2)](n)-HOSi(OtBu)(3) and Mg(AlMe(4))(2)
      HOSi(OtBu)(3) reactions, leading to the isolation of complexes of [Ba(AlEt(4))(2)
      (toluene)](2) and Mg[OSi(OtBu)(3))](2)(AlMe(3))(2), respectively. Allowing for a
      donor-induced cleavage of Mg(AlMe(4))(2), the reaction of [MgMe(2)] with one or
      two equivalents of HOSi(OtBu)(3) was studied. While putative Mg[OSi(OtBu)(3)](Me)
      and Mg[OSi(OtBu)(3)](2) could not be crystallized from the reaction mixtures,
      cluster complexes Mg(5)(O)[OSi(OtBu)(3)](5)Me(3) and
      Mg(4)(OH)(2)[OSi(OtBu)(3)](6) could be unambiguously identified by X-ray
      crystallography.

PMID- 21898624
TI  - New energetic polynitro cyclic esters: ammonium, hydrazinium, and hydroxylammonim
      salts of polynitramines.
AB  - Reaction of 2,2-dinitro-1,3-propanediol (1) with oxalyl dichloride or malonyl
      dichloride in refluxing ether led to the formation of cyclic dinitro-containing
      esters (2, 3) in very good yields. Compounds 2 and 3 were also isolated in
      similar yields by the treatment of 1 with oxalic acid or malonic acid in
      trifluoroacetic anhydride at room temperature. Nitration of 3 with fuming nitric
      acid resulted in the corresponding trinitro cyclic ester 4 in 70% isolated yield.
      Treatment of 1 with a large excess of methanolic ammonia gave impure 2,2-dinitro
      1,3-diaminopropane (5). Polynitraamines, 7 and 11, were treated with aqueous
      ammonia, hydrazine monohydrate or hydroxylamine in methanol at room temperature
      to obtain their corresponding salts 8-10 and 12-14, respectively, in excellent
      isolated yields. All new compounds were characterized by IR, NMR spectroscopy
      ((1)H, (13)C, (15)N), DSC, and elemental analysis. Their energetic properties,
      such as impact sensitivity, detonation velocity, and detonation pressure were
      also determined and compared with existing energetic compounds, such as PETN
      (pentaerythritol tetranitrate), RDX (1,3,5-trinitro-1,3,5-triazacyclohexane), and
      TNT (trinitrotoluene).

PMID- 21898625
TI  - Carbon-sulfur bond formation of challenging substrates at low temperature by
      using Pd-PEPPSI-IPent.

PMID- 21898626
TI  - The catalytic asymmetric Diels-Alder reactions and post-cycloaddition reductive
      transpositions of 1-hydrazinodienes.

PMID- 21898627
TI  - Monitoring of phenolic compounds for the quality control of Melissa officinalis
      products by capillary electrophoresis.
AB  - INTRODUCTION: Official assays for the quality control of Melissa officinalis L.
      (Lamiaceae) leaves establish the quantification of total hydroxycinnamic
      derivatives expressed as rosmarinic acid. OBJECTIVE: The goal of this work was to
      develop a simple, fast and reliable method for monitoring the phenolic
      composition in herbs from the Lamiaceae family and for rapidly detecting M.
      officinalis adulteration or substitution in commercial medicinal samples in
      Argentina. METHODOLOGY: A capillary zone electrophoresis (CZE) method was
      performed under the following conditions: the background electrolyte (BGE)
      consisted of 20 m m sodium tetraborate buffer, pH 9.2; the applied voltage was 25
      kV; the capillary and sample temperatures were kept at 25  degrees C; the
      hydrodynamic mode was selected for the sample injection (3.45 kPa during 5 s).
      RESULTS: A CZE method that achieved the separation and simultaneous determination
      of eight related phenolic compounds in less than 11 min was optimised for
      application to control quality analysis of M. officinalis-based products. The
      method was validated according to the US Federal Drug Agency requirements and
      offers advantages in terms of analysis time, cost and operation. CONCLUSIONS: The
      proposed methodology can be applied to the standardisation and quality control of
      plant material and phytopharmaceutical products derived from the Lamiaceae
      family, as indicated by the results obtained in the analysis of commercial
      medicinal products in Argentina.

PMID- 21898628
TI  - A comparative study of matrix- and nano-assisted laser desorption/ionisation time
      of-flight mass spectrometry of isolated and synthetic lignin.
AB  - INTRODUCTION: Lignin is the second most abundant biopolymer next to cellulose.
      However, because of the complexity of the heterogeneous macromolecules, it is
      difficult to elucidate the polymeric structures of lignin by conventional
      analytical methods. OBJECTIVE: To obtain the detailed structures of lignin, we
      comparatively applied nano-assisted laser desorption/ionisation time-of-flight
      mass spectrometry (NALDI-TOF MS) and matrix-assisted laser desorption/ionisation
      time-of-flight mass spectrometry (MALDI-TOF MS). METHODOLOGY: Synthetic lignin
      from coniferyl alcohol and an isolated lignin from Pinus densiflora were
      subjected to NALDI- and MALDI-TOF MS. RESULTS: We first obtained NALDI-TOF MS of
      synthetic and isolated lignin. Mass increments of 178 and 196 Da were observed in
      NALDI- and MALDI-TOF mass spectra of the synthetic and isolated lignin. The mass
      intervals indicated that radical coupling forming beta-O-4 bonds is the major
      pathway. Peaks in the low molecular mass region between m/z 500 and 800 were
      observed more extensively using NALDI-TOF MS than MALDI-TOF MS, which enabled
      detailed analysis of the interunit linkages in lignin. CONCLUSION: Owing to the
      ionisation profile differentiation from MALDI-TOF MS, NALDI-TOF MS is useful for
      the structural analysis of lignin.

PMID- 21898629
TI  - HPLC determination of flavonoid glycosides in Mongolian Dianthus versicolor
      Fisch. (Caryophyllaceae) compared with quantification by UV spectrophotometry.
AB  - INTRODUCTION: Dianthus versicolor is used in traditional Mongolian medicine
      against liver impairment. Fractions enriched in flavone-di- and triglycosides
      were shown to enhance bile secretion. Therefore, reliable and accurate analytical
      methods are needed for the determination of these flavonoids in the crude drug
      and extracts thereof. OBJECTIVE: To provide a validated HPLC-DAD (diode array
      detector) method especially developed for the separation of polar flavonoids and
      to compare the data obtained with those evaluated by UV spectrophotometry.
      METHODOLOGY: Separations were carried out on an Aquasil(r) C18-column (4.6 mm *
      250.0 mm, 5 um) with a linear gradient of acetonitrile and water (adjusted to pH
      2.8 with trifluoroacetic acid) as mobile phase. Rutoside was employed as internal
      standard with linear behavior in a concentration range of 0.007-3.5 mg/mL.
      Accuracy was determined by spiking the crude drug with saponarin resulting in
      recoveries between 92% and 102%. RESULTS: The method allows the quantification of
      highly polar flavonoid glycosides and the determination of their total content.
      For saponarin a linear response was evaluated within the range 0.007-3.5 mg/mL
      (R2  > 0.9999). It was proven that threefold sonication represents a time-saving,
      effective and cheap method for the extraction of the polar flavonoid glycosides.
      The contents determined by HPLC were shown to be in agreement with those obtained
      employing UV spectrophotometry. CONCLUSION: The study has indicated that the
      newly developed HPLC method represents a powerful technique for the quality
      control of D. versicolor. Ultraviolet spectrophotometry may be used alternatively
      provided that the less polar flavonoids are removed by purification.

PMID- 21898631
TI  - Fetal growth restriction and developmental delay: current understanding and
      future possibilities.

PMID- 21898630
TI  - The use of coupled HSQC spectra to aid in stereochemical assignments of molecules
      with severe proton spectral overlap.
AB  - INTRODUCTION: A simple glycoside with only 13 carbons exhibited extensive
      overlapping of four of the glycosidic protons, causing extreme difficulty in the
      determination of the stereochemistry of the pyranose unit. However, acquisition
      of a high-resolution coupled heteronuclear single-quantum coherence (HSQC)
      spectrum overcame this problem. This spectrum provides a useful method for
      determining vicinal proton coupling constants between strongly coupled protons.
      OBJECTIVE: To show the potential of high-resolution coupled HSQC spectra in
      overcoming spectral overlap. METHODOLOGY: The sample was obtained by methanol
      extraction, followed by fractionation and column chromatography of the dried
      leaves of Montrichardia arborescens (Araceae). NMR spectra were obtained on 1.5
      mg of sample dissolved in 120 MUL of CD3OD containing 0.1% trimethylsilyl (TMS)
      as internal standard. A gradient-selected HSQC spectrum was obtained using
      standard Varian library pulse sequences in phase sensitive mode. The high
      resolution coupled HSQC spectrum focused on the saccharide region with a 1025 Hz
      1H spectral window, a 6300 Hz 13C spectral window, 1024 data points, a 0.3 Hz
      relaxation delay, 384 time increments (linear predicted to 4096), and 80 scans
      per time increment. RESULTS: The use of a high-resolution coupled HSQC spectrum
      allowed determination of the coupling patterns of the various pyranose protons
      with sufficient accuracy. This enabled completion of the assignments and
      identification of the pyranose unit as glucose. CONCLUSION: The study has shown
      the effectiveness of the use of a high-resolution coupled HSQC spectrum in the
      assignment of molecules with severe spectral overlap.

PMID- 21898632
TI  - Ultrasound scanning of the pelvis and abdomen for staging of gynecological
      tumors: a review.
AB  - This Review documents examination techniques, sonographic features and clinical
      considerations in ultrasound assessment of gynecological tumors. The methodology
      of gynecological cancer staging, including assessment of local tumor extent,
      lymph nodes and distant metastases, is described. With increased technical
      quality, sonography has become an accurate staging method for early and advanced
      gynecological tumors. Other complementary imaging techniques, such as computed
      tomography and magnetic resonance imaging, can be used as an adjunct to
      ultrasound in specific cases, but are not essential to tumor staging if
      sonography is performed by a specialist in gynecological oncology. Ultrasound is
      established as the method of choice for evaluating local extent of endometrial
      cancer and is the most important imaging method for the differential diagnosis of
      benign and malignant ovarian tumors. Ultrasound can be used to detect early as
      well as locally advanced cancers that extend from the vagina, cervix or other
      locations to the paracolpium, parametria, rectum and sigmoid colon, urinary
      bladder and other adjacent organs or structures. In cases of ureteric
      involvement, ultrasound is also helpful in locating the site of obstruction.
      Furthermore, it is specific for the detection of extrapelvic tumor spread to the
      abdominal cavity in the form of parietal or visceral carcinomatosis, omental
      and/or mesenteric infiltration. Ultrasound can be used to assess changes in
      infiltrated lymph nodes, including demonstration of characteristic
      sonomorphologic and vascular patterns. Vascular patterns are particularly well
      visualized in peripheral nodes using high resolution linear array probes or in
      the pelvis using high-frequency probes. The presence of peripheral or mixed
      vascularity or displacement of vessels seems to be the sole criterion in the
      diagnosis of metastatic or lymphomatous nodes. In the investigation of distant
      metastases, if a normal visceral organ or characteristic diffuse or focal lesions
      (such as a simple cyst, hepatic hemangioma, renal angiomyolipoma, fatty liver
      (steatosis)) are identified on ultrasound, additional examinations using
      complementary imaging methods are not required. If, however, less characteristic
      findings are encountered, especially when the examination result radically
      affects subsequent therapeutic management, an additional examination using a
      complementary imaging method (e.g. contrast-enhanced ultrasound, computed
      tomography, magnetic resonance imaging, positron emission tomography) is
      indicated.

PMID- 21898633
TI  - Does childbirth alter the reflex pelvic floor response to coughing?
AB  - OBJECTIVE: To determine the prevalence of and to quantify the effect of reflex
      pelvic floor activation on coughing in nulliparous pregnant women, and to assess
      peripartal changes and any association with stress urinary incontinence. METHODS:
      Between April 2008 and March 2010, 131 nulliparous pregnant women were recruited
      from an antenatal clinic. All participants were interviewed and underwent four
      dimensional translabial ultrasound examination at antepartum (35.8 (mean) weeks'
      gestation) and postpartum (4.6 (mean) months) visits. Four-dimensional ultrasound
      volume datasets of the pelvic floor during coughs were obtained at a minimum
      frame rate of 16 Hz, using a 10 degrees  volume acquisition angle. To quantify a
      reflex levator contraction we measured the midsagittal hiatal diameter at
      multiple time points. Levator integrity was determined using tomographic
      ultrasound imaging. RESULTS: From 131 women recruited, 47 datasets were
      technically suboptimal, leaving 84. There was a visible pelvic floor reflex in 82
      (98%) cases. At the postpartum visit this was reduced to 63/84, i.e. 75% (P <
      0.001). The magnitude of a reflex contraction was markedly reduced postpartum,
      from 4.8 mm to 2.0 mm (P < 0.001), and this effect was associated with delivery
      mode (P = 0.042). There was a trend towards an association between lower reflex
      contraction magnitude and stress incontinence (0.87 +/- 3.18 mm vs. 2.36 +/- 3.5
      mm; P = 0.08) at the postpartum follow-up visit. CONCLUSIONS: Pelvic floor
      reflexes are altered by childbirth. This alteration may be associated with
      vaginal delivery. Reflex magnitude may be associated with postpartum stress
      urinary incontinence. The clinical significance of this finding is uncertain.

PMID- 21898634
TI  - Ultrasonographic and laboratory markers of metabolic and cardiovascular disease
      risk in obese women with polycystic ovary syndrome.
AB  - OBJECTIVE: To evaluate whether the presence of polycystic ovary syndrome (PCOS)
      alters multiple ultrasonographic and laboratory markers of metabolic and
      cardiovascular disease risk in obese women without any other health condition
      that could interfere with combined oral contraceptive (COC) eligibility criteria.
      METHODS: This was a case-control study evaluating 90 obese women (body mass index
      (BMI) >= 30.0 kg/m(2) and < 40 kg/m(2)) aged between 18 and 40 years without any
      other health condition that could interfere with COC eligibility criteria, of
      whom 45 had PCOS and 45 were age-matched controls. BMI, waist and hip
      circumference, arterial blood pressure, fasting insulin and glucose, quantitative
      insulin sensitivity check index (QUICKI), high-density lipoprotein cholesterol,
      low-density lipoprotein cholesterol, total cholesterol, triglycerides,
      testosterone, sex hormone-binding globulin, free androgen index (FAI), carotid
      stiffness index, intima media thickness, flow-mediated dilatation (FMD) of the
      brachial artery and non-alcoholic fatty liver disease (NAFLD) were assessed.
      RESULTS: In women with PCOS, we observed a higher frequency of NAFLD (73.3 vs.
      46.7%, P < 0.01) and higher FAI (10.4 vs. 6.8%, P < 0.01). We also observed a
      trend towards increased insulin levels (10.06 +/- 6.66 vs. 7.45 +/- 5.88 uIU/mL,
      P = 0.05), decreased QUICKI (0.36 +/- 0.06 vs. 0.39 +/- 0.07, P = 0.05) and
      decreased FMD (7.00 +/- 3.87 vs. 8.41 +/- 3.79%, P = 0.08). No other significant
      difference was observed. CONCLUSIONS: NAFLD is frequent in obese women without
      any other health condition that could interfere with COC eligibility criteria,
      especially in those with PCOS. This should be considered when choosing the best
      contraceptive option.

PMID- 21898635
TI  - Advantages of the population-based approach to pregnancy dating: results from
      23,020 ultrasound examinations.
AB  - OBJECTIVE: To confirm the results from two previous evaluations of term
      prediction models, including two sample-based models and one population-based
      model, in a third population. METHODS: In a study population of 23,020 second
      trimester ultrasound examinations, data were prospectively collected and
      registered over the period 1988-2009. Three different models for ultrasonically
      estimated date of delivery were applied to the measurements of fetal biparietal
      diameter (BPD) and two models were applied to the femur length (FL) measurements;
      the resulting term estimations were compared with the actual time of delivery.
      The difference between the actual and the predicted dates of delivery (the median
      bias) was calculated for each of the models, for three BPD/FL-measurement
      subgroups and for the study population as a whole. RESULTS: For the population
      based model, the median bias was + 0.4 days for the BPD-based predictions and -
      0.4 days for the FL-based predictions, and the biases were stable over the
      inclusion ranges. The biases of the two traditional models varied with the size
      of the fetus at examination; median biases were - 0.87 and + 2.2 days,
      respectively, with extremes - 4.2 and + 4.8 days for the BPD-based predictions,
      and the median bias was + 1.72 days with range - 0.8 to + 4.5 days for FL-based
      predictions. The disagreement between the two sample-based models was never less
      than 2 days for the BPD-based predictions. CONCLUSION: This study confirms the
      results from previous studies; median biases were negligible with term
      predictions from the population-based model, while those from the traditional
      models varied substantially. The biases, which have clinical implications, seem
      inevitable with the sample-based models, which, even if overall biases were
      removed, will perform unsatisfactorily.

PMID- 21898636
TI  - Relationship between sonographically estimated fetal subcutaneous adipose tissue
      measurements and neonatal skinfold measurements.
AB  - OBJECTIVE: Increased subcutaneous adipose tissue is a well known characteristic
      of diabetic fetopathy. Prenatal estimation of adipose tissue can be performed by
      ultrasound, while postnatally skinfold measurements are performed using a Holtain
      caliper. The aim of this study was to compare these methods in the same patients.
      METHODS: This was a prospective study of 172 pregnant patients (142 controls and
      30 with gestational diabetes) at >= 37 gestational weeks. In addition to fetal
      weight estimation, fetal subcutaneous tissue was measured at the anterior abdomen
      lateral to the umbilicus (SonoSfAbd) and at the middle of the femur (SonoSfFem).
      Within 72 h after delivery, a Holtain caliper was used to measure neonatal
      skinfold thickness at the left anterior iliac spine (SfAbd), at the lower angle
      of the left scapula (SfSca), at the middle of the femur, above the left
      quadriceps femoris (SfFem) and at the middle of the left triceps (SfHum).
      Ultrasound and mechanical measurements were correlated. RESULTS: The sonographic
      and mechanical methods showed good correlation with each other. Linear regression
      analysis gave the following equations: SfAbd (mm) = SonoSfAbd (mm) * 0.489 +
      1.988 (r(2) = 0.34, P < 0.001); SfSca (mm) = SonoSfAbd (mm) 0.457 + 2.043 (r(2) =
      0.40, P < 0.001); SfFem (mm) = SonoSfFem (mm) * 0.714 + 1.763 (r(2) = 0.41, P <
      0.001); SfHum (mm) = SonoSfFem (mm) 0.564 + 2.09 (r(2) = 0.39, P < 0.001).
      CONCLUSIONS: Ultrasound examination is a reliable method for non-invasive
      intrauterine measurement of fetal subcutaneous tissue and can be used to predict
      mechanical neonatal skinfold thickness measurements.

PMID- 21898637
TI  - Maximal amniotic fluid index as a prognostic factor in pregnancies complicated by
      polyhydramnios.
AB  - OBJECTIVES: Polyhydramnios is present in approximately 2% of pregnancies and has
      been associated with a variety of adverse pregnancy outcomes. Our aim was to
      evaluate the association between the maximal amniotic fluid index (AFI) and the
      frequency of specific adverse outcomes. METHODS: This was a retrospective chart
      review of 524 singleton pregnancies diagnosed with polyhydramnios and delivered
      in a single tertiary referral center between 2003 and 2008. Polyhydramnios was
      defined as either AFI >= 25 cm or a maximum vertical pocket (MVP) >= 8 cm even in
      the presence of AFI < 25 cm. The cohort was stratified into four groups based on
      the maximal AFI noted during the pregnancy: < 25 cm but with MVP >= 8 cm; 25-29.9
      cm; 30-34.9 cm; and >= 35 cm. Data were collected to determine the frequency of
      the following adverse pregnancy outcomes: prenatally diagnosed congenital
      anomalies, fetal aneuploidy, preterm delivery, Cesarean delivery, low birth
      weight, 5-min Apgar score < 7 and perinatal mortality. RESULTS: Higher AFI was
      associated with a statistically significant increase in the frequency of adverse
      pregnancy outcomes. The most severe form of polyhydramnios, as based on the
      maximal AFI (>= 35 cm; n = 67), was associated with the highest rates of
      prenatally diagnosed congenital anomalies (79%), preterm delivery (46%), small
      for-gestational-age neonate (16%), aneuploidy (13%) and perinatal mortality
      (27%). No significant association between degree of polyhydramnios and adverse
      outcome was demonstrated in cases of idiopathic polyhydramnios (n = 253).
      CONCLUSIONS: There is an association between the frequencies of a variety of
      adverse pregnancy outcomes and the severity of polyhydramnios as reflected by the
      maximal AFI.

PMID- 21898638
TI  - What are the limits of accuracy in fetal weight estimation with conventional
      biometry in two-dimensional ultrasound? A novel postpartum study.
AB  - OBJECTIVE: Commonly used formulae for fetal weight estimation, including
      combinations of several biometric parameters, lack accuracy despite efforts to
      improve them. This study aimed to investigate the limits of fetal weight
      estimation based on conventional biometric parameters on two-dimensional (2D)
      ultrasound by developing and evaluating new weight equations using postpartum
      biometric parameters. METHODS: This was a prospective multicenter study including
      628 singleton pregnancies at term. Inclusion criteria were healthy newborns with
      no physical or chromosomal malformations. Postpartum measurement of head
      circumference, abdominal circumference and thigh length was performed. Six 'best
      fit' formulae were derived using forward regression analysis in a formula-finding
      group (n = 419), and their accuracy was compared with birth weight in an
      evaluation group (n = 209) using percentage error, absolute percentage error,
      limits of agreement and the proportion of weight estimations falling within a
      discrepancy level of +/- 10%. RESULTS: The new formulae showed no systematic
      error, with SD for the percentage error between 7.42 and 8.77 and no significant
      differences between median absolute percentage errors (4.84-5.71). They included
      74.6-81.3% of neonates within a discrepancy level of 10%. With regard to the 95%
      limits of agreement, weight estimates were within a range of about +/- 500 g.
      CONCLUSION: These results show that a good sonographic weight formula has the
      following features: no systematic error, an SD of about 7% and inclusion of 80%
      of cases within a discrepancy level of 10%. The study indicates that the current
      accuracy of fetal weight estimation with conventional biometric parameters by 2D
      ultrasound has reached its limits. Further improvement will probably only be
      achieved through new approaches in ultrasonography.

PMID- 21898639
TI  - Prediction and probability of neonatal outcome in isolated congenital
      diaphragmatic hernia using multiple ultrasound parameters.
AB  - OBJECTIVES: To evaluate the accuracy and probabilities of different fetal
      ultrasound parameters to predict neonatal outcome in isolated congenital
      diaphragmatic hernia (CDH). METHODS: Between January 2004 and December 2010, we
      evaluated prospectively 108 fetuses with isolated CDH (82 left-sided and 26 right
      sided). The following parameters were evaluated: gestational age at diagnosis,
      side of the diaphragmatic defect, presence of polyhydramnios, presence of liver
      herniated into the fetal thorax (liver-up), lung-to-head ratio (LHR) and
      observed/expected LHR (o/e-LHR), observed/expected contralateral and total fetal
      lung volume (o/e-ContFLV and o/e-TotFLV) ratios, ultrasonographic fetal lung
      volume/fetal weight ratio (US-FLW), observed/expected contralateral and main
      pulmonary artery diameter (o/e-ContPA and o/e-MPA) ratios and the contralateral
      vascularization index (Cont-VI). The outcomes were neonatal death and severe
      postnatal pulmonary arterial hypertension (PAH). RESULTS: Neonatal mortality was
      64.8% (70/108). Severe PAH was diagnosed in 68 (63.0%) cases, of which 63 died
      neonatally (92.6%) (P < 0.001). Gestational age at diagnosis, side of the defect
      and polyhydramnios were not associated with poor outcome (P > 0.05). LHR, o/e
      LHR, liver-up, o/e-ContFLV, o/e-TotFLV, US-FLW, o/e-ContPA, o/e-MPA and Cont-VI
      were associated with both neonatal death and severe postnatal PAH (P < 0.001).
      Receiver-operating characteristics curves indicated that measuring total lung
      volumes (o/e-TotFLV and US-FLW) was more accurate than was considering only the
      contralateral lung sizes (LHR, o/e-LHR and o/e-ContFLV; P < 0.05), and Cont-VI
      was the most accurate ultrasound parameter to predict neonatal death and severe
      PAH (P < 0.001). CONCLUSIONS: Evaluating total lung volumes is more accurate than
      is measuring only the contralateral lung size. Evaluating pulmonary
      vascularization (Cont-VI) is the most accurate predictor of neonatal outcome.
      Estimating the probability of survival and severe PAH allows classification of
      cases according to prognosis.

PMID- 21898640
TI  - Simultaneous recordings of pulsed wave Doppler signals in hepatic vein and
      descending aorta using dual Doppler: a novel method for evaluating fetal
      arrhythmias.

PMID- 21898641
TI  - Generation of monospecific antibodies based on affinity capture of polyclonal
      antibodies.
AB  - A method is described to generate and validate antibodies based on mapping the
      linear epitopes of a polyclonal antibody followed by sequential epitope-specific
      capture using synthetic peptides. Polyclonal antibodies directed towards four
      proteins RBM3, SATB2, ANLN, and CNDP1, potentially involved in human cancers,
      were selected and antibodies to several non-overlapping epitopes were generated
      and subsequently validated by Western blot, immunohistochemistry, and
      immunofluorescence. For all four proteins, a dramatic difference in functionality
      could be observed for these monospecific antibodies directed to the different
      epitopes. In each case, at least one antibody was obtained with full
      functionality across all applications, while other epitope-specific fractions
      showed no or little functionality. These results present a path forward to use
      the mapped binding sites of polyclonal antibodies to generate epitope-specific
      antibodies, providing an attractive approach for large-scale efforts to
      characterize the human proteome by antibodies.

PMID- 21898642
TI  - Binding and inhibition of human spermidine synthase by decarboxylated S
      adenosylhomocysteine.
AB  - Aminopropyltransferases are essential enzymes that form polyamines in eukaryotic
      and most prokaryotic cells. Spermidine synthase (SpdS) is one of the most well
      studied enzymes in this biosynthetic pathway. The enzyme uses decarboxylated S
      adenosylmethionine and a short-chain polyamine (putrescine) to make a medium
      chain polyamine (spermidine) and 5'-deoxy-5'-methylthioadenosine as a byproduct.
      Here, we report a new spermidine synthase inhibitor, decarboxylated S
      adenosylhomocysteine (dcSAH). The inhibitor was synthesized, and dose-dependent
      inhibition of human, Thermatoga maritima, and Plasmodium falciparum spermidine
      synthases, as well as functionally homologous human spermine synthase, was
      determined. The human SpdS/dcSAH complex structure was determined by X-ray
      crystallography at 2.0 A resolution and showed consistent active site positioning
      and coordination with previously known structures. Isothermal calorimetry binding
      assays confirmed inhibitor binding to human SpdS with K(d)  of 1.1 +/- 0.3 MUM in
      the absence of putrescine and 3.2 +/- 0.1 MUM in the presence of putrescine.
      These results indicate a potential for further inhibitor development based on the
      dcSAH scaffold.

PMID- 21898645
TI  - Surviving the sun: repair and bypass of DNA UV lesions.
AB  - Structural studies of UV-induced lesions and their complexes with repair proteins
      reveal an intrinsic flexibility of DNA at lesion sites. Reduced DNA rigidity
      stems primarily from the loss of base stacking, which may manifest as bending,
      unwinding, base unstacking, or flipping out. The intrinsic flexibility at UV
      lesions allows efficient initial lesion recognition within a pool of millions to
      billions of normal DNA base pairs. To bypass the damaged site by translesion
      synthesis, the specialized DNA polymerase eta acts like a molecular "splint" and
      reinforces B-form DNA by numerous protein-phosphate interactions. Photolyases and
      glycosylases that specifically repair UV lesions interact directly with UV
      lesions in bent DNA via surface complementation. UvrA and UvrB, which recognize a
      variety of lesions in the bacterial nucleotide excision repair pathway, appear to
      exploit hysteresis exhibited by DNA lesions and conduct an ATP-dependent stress
      test to distort and separate DNA strands. Similar stress tests are likely
      conducted in eukaryotic nucleotide excision repair.

PMID- 21898646
TI  - Comment on "Revisiting the Ramachandran plot from a new angle".

PMID- 21898647
TI  - High-resolution structure prediction of a circular permutation loop.
AB  - Methods for rapid and reliable design and structure prediction of linker loops
      would facilitate a variety of protein engineering applications. Circular
      permutation, in which the existing termini of a protein are linked by the
      polypeptide chain and new termini are created, is one such application that has
      been employed for decreasing proteolytic susceptibility and other functional
      purposes. The length and sequence of the linker can impact the expression level,
      solubility, structure and function of the permuted variants. Hence it is
      desirable to achieve atomic-level accuracy in linker design. Here, we describe
      the use of RosettaRemodel for design and structure prediction of circular
      permutation linkers on a model protein. A crystal structure of one of the
      permuted variants confirmed the accuracy of the computational prediction, where
      the all-atom rmsd of the linker region was 0.89 A between the model and the
      crystal structure. This result suggests that RosettaRemodel may be generally
      useful for the design and structure prediction of protein loop regions for
      circular permutations or other structure-function manipulations.

PMID- 21898648
TI  - The interplay between transient alpha-helix formation and side chain rotamer
      distributions in disordered proteins probed by methyl chemical shifts.
AB  - The peptide backbones of disordered proteins are routinely characterized by NMR
      with respect to transient structure and dynamics. Little experimental information
      is, however, available about the side chain conformations and how structure in
      the backbone affects the side chains. Methyl chemical shifts can in principle
      report the conformations of aliphatic side chains in disordered proteins and in
      order to examine this two model systems were chosen: the acid denatured state of
      acyl-CoA binding protein (ACBP) and the intrinsically disordered activation
      domain of the activator for thyroid hormone and retinoid receptors (ACTR). We
      find that small differences in the methyl carbon chemical shifts due to the gamma
      gauche effect may provide information about the side chain rotamer distributions.
      However, the effects of neighboring residues on the methyl group chemical shifts
      obscure the direct observation of gamma-gauche effect. To overcome this, we
      reference the chemical shifts to those in a more disordered state resulting in
      residue specific random coil chemical shifts. The (13)C secondary chemical shifts
      of the methyl groups of valine, leucine, and isoleucine show sequence specific
      effects, which allow a quantitative analysis of the ensemble of chi(2)-angles of
      especially leucine residues in disordered proteins. The changes in the rotamer
      distributions upon denaturation correlate to the changes upon helix induction by
      the co-solvent trifluoroethanol, suggesting that the side chain conformers are
      directly or indirectly related to formation of transient alpha-helices.

PMID- 21898650
TI  - Determination of the amino acid sequence requirements for catalysis by the highly
      proficient orotidine monophosphate decarboxylase.
AB  - Orotidine 5'-monophosphate decarboxylase (ODCase) catalyzes the decarboxylation
      of orotidine 5'-monophosphate to uridine 5'-monophosphate during pyrimidine
      nucleotide biosynthesis. This enzyme is one of the most proficient known,
      exhibiting a rate enhancement of over 17 orders of magnitude over the uncatalyzed
      rate. An interesting question is whether the high proficiency of ODCase is
      associated with a highly optimized sequence of active site residues. This
      question was addressed by randomizing 24 residue positions in and around the
      active site of the E. coli ODCase (pyrF) by site-directed mutagenesis. The
      libraries of mutants were selected for function from a multicopy plasmid or by
      single-copy replacement at the pyrF locus on the E. coli chromosome. Stringent
      sequence requirements for function were found for the mutants expressed from the
      chromosomal pyrF locus. Six positions were not tolerant of substitutions and
      several others accepted very limited substitutions. In contrast, all positions
      could be substituted to some extent when the library mutants were expressed from
      a multicopy plasmid. For the conserved quartet of charged residues Lys44-Asp71
      Lys73-Asp76, a cysteine substitution was found to provide function at positions
      71 and 76. A lower pK(a)  for both cysteine mutants supports a mechanism whereby
      the thiolate group of cysteine substitutes for the negatively charged aspartate
      side chain. The partial function mutants such as D71C and D76C exhibit reduced
      catalytic efficiency relative to wild type but nevertheless provide a rate
      enhancement of 15 orders of magnitude over the uncatalyzed rate indicating the
      catalytic proficiency of the enzyme is robust and tolerant of mutation.

PMID- 21898649
TI  - An approach to crystallizing proteins by metal-mediated synthetic symmetrization.
AB  - Combining the concepts of synthetic symmetrization with the approach of
      engineering metal-binding sites, we have developed a new crystallization
      methodology termed metal-mediated synthetic symmetrization. In this method, pairs
      of histidine or cysteine mutations are introduced on the surface of target
      proteins, generating crystal lattice contacts or oligomeric assemblies upon
      coordination with metal. Metal-mediated synthetic symmetrization greatly expands
      the packing and oligomeric assembly possibilities of target proteins, thereby
      increasing the chances of growing diffraction-quality crystals. To demonstrate
      this method, we designed various T4 lysozyme (T4L) and maltose-binding protein
      (MBP) mutants and cocrystallized them with one of three metal ions: copper (Cu2+,
      nickel (Ni2+), or zinc (Zn2+). The approach resulted in 16 new crystal structures
      -eight for T4L and eight for MBP--displaying a variety of oligomeric assemblies
      and packing modes, representing in total 13 new and distinct crystal forms for
      these proteins. We discuss the potential utility of the method for crystallizing
      target proteins of unknown structure by engineering in pairs of histidine or
      cysteine residues. As an alternate strategy, we propose that the varied
      crystallization-prone forms of T4L or MBP engineered in this work could be used
      as crystallization chaperones, by fusing them genetically to target proteins of
      interest.

PMID- 21898651
TI  - A tale of two GTPases in cotranslational protein targeting.
AB  - Guanosine triphosphatases (GTPases) comprise a superfamily of proteins that
      provide molecular switches to regulate numerous cellular processes. The "GTPase
      switch" paradigm, in which a GTPase acts as a bimodal switch that is turned "on"
      and "off" by external regulatory factors, has been used to interpret the
      regulatory mechanism of many GTPases. Recent work on a pair of GTPases in the
      signal recognition particle (SRP) pathway has revealed a distinct mode of GTPase
      regulation. Instead of the classical GTPase switch, the two GTPases in the SRP
      and SRP receptor undergo a series of conformational changes during their
      dimerization and reciprocal activation. Each conformational rearrangement
      provides a point at which these GTPases can communicate with and respond to their
      upstream and downstream biological cues, thus ensuring the spatial and temporal
      precision of all the molecular events in the SRP pathway. We suggest that the SRP
      and SRP receptor represent an emerging class of "multistate" regulatory GTPases
      uniquely suited to provide exquisite control over complex cellular pathways that
      require multiple molecular events to occur in a highly coordinated fashion.

PMID- 21898653
TI  - Rational disruption of the oligomerization of the mini-ferritin E. coli DPS
      through protein-protein interface mutation.
AB  - DNA-binding protein from starved cells (DPS), a mini-ferritin capable of self
      assembling into a 12-meric nano-cage, was chosen as the basis for an alanine
      shaving mutagenesis study to investigate the importance of key amino acid
      residues, located at symmetry-related protein-protein interfaces, in controlling
      protein stability and self-assembly. Nine mutants were designed through simple
      inspection, synthesized, and subjected to transmission electron microscopy,
      circular dichroism, size exclusion chromatography, and "virtual alanine scanning"
      computational analysis. The data indicate that many of these residues may be hot
      spot residues. Most remarkably, two residues, R83 and R133, were observed to
      shift the oligomerization state to ~50% dimer. Based on the hypothesis that these
      two residues constitute a "hot strip," located at the ferritin-like threefold
      axis, the double mutant was generated which completely shuts down detectable
      formation of 12-mer in solution, favoring a cooperatively folded dimer. The fact
      that this effect logically builds upon the single mutants emphasizes that complex
      self-assembly has the potential to be manipulated rationally. This study should
      have an impact on the fundamental understanding of the assembly of DPS protein
      cages specifically and protein quaternary structure in general. In addition, as
      there is much interest in applying these and similar systems to the templation of
      nano-materials and drug delivery, the ability to control this ferritin's
      oligomerization state and stability could prove especially valuable.

PMID- 21898652
TI  - A structural study of Hypocrea jecorina Cel5A.
AB  - Interest in generating lignocellulosic biofuels through enzymatic hydrolysis
      continues to rise as nonrenewable fossil fuels are depleted. The high cost of
      producing cellulases, hydrolytic enzymes that cleave cellulose into fermentable
      sugars, currently hinders economically viable biofuel production. Here, we report
      the crystal structure of a prevalent endoglucanase in the biofuels industry,
      Cel5A from the filamentous fungus Hypocrea jecorina. The structure reveals a
      general fold resembling that of the closest homolog with a high-resolution
      structure, Cel5A from Thermoascus aurantiacus. Consistent with previously
      described endoglucanase structures, the H. jecorina Cel5A active site contains a
      primarily hydrophobic substrate binding groove and a series of hydrogen bond
      networks surrounding two catalytic glutamates. The reported structure, however,
      demonstrates stark differences between side-chain identity, loop regions, and the
      number of disulfides. Such structural information may aid efforts to improve the
      stability of this protein for industrial use while maintaining enzymatic activity
      through revealing nonessential and immutable regions.

PMID- 21898654
TI  - HLA-DP2 binding prediction by molecular dynamics simulations.
AB  - Major histocompatibility complex (MHC) II proteins bind peptide fragments derived
      from pathogen antigens and present them at the cell surface for recognition by T
      cells. MHC proteins are divided into Class I and Class II. Human MHC Class II
      alleles are grouped into three loci: HLA-DP, HLA-DQ, and HLA-DR. They are
      involved in many autoimmune diseases. In contrast to HLA-DR and HLA-DQ proteins,
      the X-ray structure of the HLA-DP2 protein has been solved quite recently. In
      this study, we have used structure-based molecular dynamics simulation to derive
      a tool for rapid and accurate virtual screening for the prediction of HLA-DP2
      peptide binding. A combinatorial library of 247 peptides was built using the
      "single amino acid substitution" approach and docked into the HLA-DP2 binding
      site. The complexes were simulated for 1 ns and the short range interaction
      energies (Lennard-Jones and Coulumb) were used as binding scores after
      normalization. The normalized values were collected into quantitative matrices
      (QMs) and their predictive abilities were validated on a large external test set.
      The validation shows that the best performing QM consisted of Lennard-Jones
      energies normalized over all positions for anchor residues only plus cross terms
      between anchor-residues.

PMID- 21898656
TI  - First- and second-shell metal binding residues in human proteins are
      disproportionately associated with disease-related SNPs.
AB  - Protein structure serves as a key determinant for revealing the molecular basis
      of human disease. Metal ions are among the most frequently bound heterogroups in
      proteins affecting structure and function. We analyzed the relationship between
      single nucleotide polymorphisms (SNPs) associated with human disease and metal
      binding sites in proteins on a database scale, using structural models and
      predictive tools. A match was identified for 586 disease-associated SNPs (dSNPs)
      located at 135 predicted metal binding sites and associated with 126 diverse
      diseases. For 104 diseases, a metal is known to bind at the predicted site in the
      homologue; for 22, the analysis gives a first indication for metal involvement in
      the disease. As second-shell residues play an important part in metal ion
      binding, our analysis included protein space up to 4.5 A from metal binding
      sites. The ratio of disease-associated versus nondisease-associated SNPs
      (dSNP/ndSNP) for first-shell residues is 7.4 and for second-shell residues, 3.1.
      In addition, over 13% of all dSNPs were found to be associated with first- and
      second-shell residues, although these residues occupy only about 3% of protein
      space. These results show a disproportionate association of dSNPs and metal
      binding sites over a wide variety of diseases.

PMID- 21898655
TI  - Self-efficacy and fear of cancer progression during the year following diagnosis
      of breast cancer.
AB  - OBJECTIVE: The aim of this study was to investigate fear of disease progression
      (FoP) during the year following diagnosis of breast cancer and its association
      with general self-efficacy (SE). METHODS: In a prospective study, 118 breast
      cancer patients were recruited shortly after diagnosis disclosure (response rate:
      54%) and at 1-year follow-up (follow-up rate: 90%). Participants completed self
      report measures of general self-efficacy (General Self-Efficacy Scale) and fear
      of progression (short form of the Fear of Progression Questionnaire). RESULTS:
      Cross-sectional regression analysis revealed that high FoP is significantly
      associated with low SE, even when controlling for demographic and medical
      characteristics (total R2 = 0.17). Having children and a relatively short time
      since diagnosis also significantly predicted higher FoP. Longitudinal analyses
      showed that FoP decreased significantly over time (p = 0.001; d = 0.25), but a
      significant decrease was only observed for patients with high initial FoP (p <
      0.001; d = 0.74) and not for those with low initial FoP (p = 0.688; d = 0.08). SE
      was not a significant predictor of FoP at follow-up when controlling for initial
      FoP and other patient characteristics (incremental R2 = 0.001; p = 0.674; total
      R2 = 0.47). Overall, only initial FoP significantly predicted FoP at follow-up (p
      < 0.001; beta = 0.671). CONCLUSION: Findings that low SE is associated with high
      FoP can help to improve the treatment of dysfunctional fears in breast cancer
      patients. As FoP changes only slightly over time, treatment to enhance SE and
      reduce FoP should be initiated soon after disease disclosure.

PMID- 21898657
TI  - A functional XPNPEP2 promoter haplotype leads to reduced plasma aminopeptidase P
      and increased risk of ACE inhibitor-induced angioedema.
AB  - Angiotensin I-converting enzyme inhibitors (ACEi) are widely used
      antihypertensive agents that are associated with a potentially life-threatening
      reaction, ACEi-angioedema. Impaired metabolism of bradykinin and des-Arg(9) 
      bradykinin by aminopeptidase P (APP) is a key contributor to ACEi-angioedema.
      This study aimed to characterize the genetic regulation of the XPNPEP2 gene and
      identify the genetic factors contributing to variance in plasma APP activity and
      ACEi-angioedema. Additive genetic factors accounted for 47.3% of variance in
      plasma APP activity in healthy individuals. Nested deletion analysis identified
      the minimal promoter (-338 bp to -147 bp) and an enhancer region (-2,502 bp to 
      2,238 bp). Three polymorphisms (c.-2399C>A, c.-1612G>T, and c.-393G>A) were
      significantly associated with plasma APP activity. Haplotype ATG was
      significantly associated with reduced reporter gene activity and with reduced
      plasma APP activity. The c.-2399C>A polymorphism was located in an enhancer
      region and was predicted to differentially bind hepatic nuclear factor 4 (HNF4).
      Over expression of HNF4 increased the activation of haplotype ATG compared with
      haplotype CGG. In a case control study of subjects with a history of ACEi
      angioedema, haplotype ATG was significantly associated with ACEi-angioedema (OR
      4.87 [1.78-13.35] P = 0.002). The ATG haplotype is functional and contributes to
      ACEi-angioedema through a reduction in APP.

PMID- 21898658
TI  - Identification and functional analysis of SOX10 missense mutations in different
      subtypes of Waardenburg syndrome.
AB  - Waardenburg syndrome (WS) is a rare disorder characterized by pigmentation
      defects and sensorineural deafness, classified into four clinical subtypes, WS1
      S4. Whereas the absence of additional features characterizes WS2, association
      with Hirschsprung disease defines WS4. WS is genetically heterogeneous, with six
      genes already identified, including SOX10. About 50 heterozygous SOX10 mutations
      have been described in patients presenting with WS2 or WS4, with or without
      myelination defects of the peripheral and central nervous system (PCWH,
      Peripheral demyelinating neuropathy-Central dysmyelinating leukodystrophy
      Waardenburg syndrome-Hirschsprung disease, or PCW, PCWH without HD). The majority
      are truncating mutations that most often remove the main functional domains of
      the protein. Only three missense mutations have been thus far reported. In the
      present study, novel SOX10 missense mutations were found in 11 patients and were
      examined for effects on SOX10 characteristics and functions. The mutations were
      associated with various phenotypes, ranging from WS2 to PCWH. All tested
      mutations were found to be deleterious. Some mutants presented with partial
      cytoplasmic redistribution, some lost their DNA-binding and/or transactivation
      capabilities on various tissue-specific target genes. Intriguingly, several
      mutants were redistributed in nuclear foci. Whether this phenomenon is a cause or
      a consequence of mutation-associated pathogenicity remains to be determined, but
      this observation could help to identify new SOX10 modes of action.

PMID- 21898659
TI  - Rapid and efficient human mutation detection using a bench-top next-generation
      DNA sequencer.
AB  - Next-generation sequencing (NGS) technologies can be a boon to human mutation
      detection given their high throughput: consequently, many genes and samples may
      be simultaneously studied with high coverage for accurate detection of
      heterozygotes. In circumstances requiring the intensive study of a few genes,
      particularly in clinical applications, a rapid turn around is another desirable
      goal. To this end, we assessed the performance of the bench-top 454 GS Junior
      platform as an optimized solution for mutation detection by amplicon sequencing
      of three type 3 semaphorin genes SEMA3A, SEMA3C, and SEMA3D implicated in
      Hirschsprung disease (HSCR). We performed mutation detection on 39 PCR amplicons
      totaling 14,014 bp in 47 samples studied in pools of 12 samples. Each 10-hr run
      was able to generate ~75,000 reads and ~28 million high-quality bases at an
      average read length of 371 bp. The overall sequencing error was 0.26 changes per
      kb at a coverage depth of >=20 reads. Altogether, 37 sequence variants were found
      in this study of which 10 were unique to HSCR patients. We identified five
      missense mutations in these three genes that may potentially be involved in the
      pathogenesis of HSCR and need to be studied in larger patient samples.

PMID- 21898660
TI  - Dilated cardiomyopathy-associated BAG3 mutations impair Z-disc assembly and
      enhance sensitivity to apoptosis in cardiomyocytes.
AB  - Dilated cardiomyopathy (DCM) is characterized by dilation of left ventricular
      cavity with systolic dysfunction. Clinical symptom of DCM is heart failure, often
      associated with cardiac sudden death. About 20-35% of DCM patients have apparent
      family histories and it has been revealed that mutations in genes for sarcomere
      proteins cause DCM. However, the disease-causing mutations can be found only in
      about 17% of Japanese patients with familial DCM. Bcl-2-associated athanogene 3
      (BAG3) is a co-chaperone protein with antiapoptotic function, which localizes at
      Z-disc in the striated muscles. Recently, BAG3 gene mutations in DCM patients
      were reported, but the functional abnormalities caused by the mutations are not
      fully unraveled. In this study, we analyzed 72 Japanese familial DCM patients for
      mutations in BAG3 and found two mutations, p.Arg218Trp and p.Leu462Pro, in two
      cases of adult-onset DCM without skeletal myopathy, which were absent from 400
      control subjects. Functional studies at the cellular level revealed that the DCM
      associated BAG3 mutations impaired the Z-disc assembly and increased the
      sensitivities to stress-induced apoptosis. These observations suggested that BAG3
      mutations present in 2.8% of Japanese familial DCM patients caused DCM possibly
      by interfering with Z-disc assembly and inducing apoptotic cell death under the
      metabolic stress.

PMID- 21898662
TI  - Molecular genetic characterization of SMAD signaling molecules in pulmonary
      arterial hypertension.
AB  - Heterozygous germline mutations of BMPR2 contribute to familial clustering of
      pulmonary arterial hypertension (PAH). To further explore the genetic basis of
      PAH in isolated cases, we undertook a candidate gene analysis to identify
      potentially deleterious variation. Members of the bone morphogenetic protein
      (BMP) pathway, namely SMAD1, SMAD4, SMAD5, and SMAD9, were screened by direct
      sequencing for gene defects. Four variants were identified in SMADs 1, 4, and 9
      among a cohort of 324 PAH cases, each not detected in a substantial control
      population. Of three amino acid substitutions identified, two demonstrated
      reduced signaling activity in vitro. A putative splice site mutation in SMAD4
      resulted in moderate transcript loss due to compromised splicing efficiency.
      These results demonstrate the role of BMPR2 mutation in the pathogenesis of PAH
      and indicate that variation within the SMAD family represents an infrequent cause
      of the disease.

PMID- 21898663
TI  - Ultrastructural aspects of Callithrix penicillata lingual papillae.
AB  - Callithrix penicillata belongs to the family Callitrichidae, Callithrix genus.
      They are basically insectivorous, but they consume fruits. The mucosa of the
      tongue is composed of some papillary types, revealing different levels of
      expertise. The present study attempted to describe the morphological and
      ultrastructural aspects of the dorsal surface of the C. penicillata, describing
      the characteristics and distribution of papillae found. Five tongues of C.
      penicillata (two females and three males), obtained from breeding colonies of
      CENP-Ananindeua-PA, died from natural causes. The material was fixed partly in a
      buffer solution paraformaldehyde 10% and partly in modified Karnovsky solution,
      divided into apex, body, and root, and then the fragments were used in light
      microscopy and scanning electron microscopy. The average length of the tongue of
      the females was 22 mm and for males 20.5 mm. Three types of papillae were
      described: filiform (along all tissue extension with 154 MUm of diameter),
      fungiform (along all tissue extension with 275 MUm of diameter), and vallate
      (just three units in caudal (dorsal) portion with 672 MUm of diameter). Data
      analysis indicates that the distribution and ultrastructural morphology of the C.
      penicillata lingual papillae are some similar to other primates.

PMID- 21898661
TI  - Variants in activators and downstream targets of ATM, radiation exposure, and
      contralateral breast cancer risk in the WECARE study.
AB  - Ionizing radiation (IR) is a breast carcinogen that induces DNA double-strand
      breaks (DSBs), and variation in genes involved in the DNA DSB response has been
      implicated in radiation-induced breast cancer. The Women's Environmental, Cancer,
      and Radiation Epidemiology (WECARE) study is a population-based study of cases
      with contralateral breast cancer (CBC) and matched controls with unilateral
      breast cancer. The location-specific radiation dose received by the contralateral
      breast was estimated from radiotherapy records and mathematical models. One
      hundred fifty-two SNPs in six genes (CHEK2, MRE11A, MDC1, NBN, RAD50, TP53BP1)
      involved in the DNA DSBs response were genotyped. No variants or haplotypes were
      associated with CBC risk (649 cases and 1,284 controls) and no variants were
      found to interact with radiation dose. Carriers of a RAD50 haplotype exposed to
      >=1 gray (Gy) had an increased risk of CBC compared with unexposed carriers (Rate
      ratios [RR] = 4.31 [95% confidence intervals [CI] 1.93-9.62]); with an excess
      relative risk (ERR) per Gy = 2.13 [95% CI 0.61-5.33]). Although the results of
      this study were largely null, carriers of a haplotype in RAD50 treated with
      radiation had a greater CBC risk than unexposed carriers. This suggests that
      carriers of this haplotype may be susceptible to the DNA-damaging effects of
      radiation therapy associated with radiation-induced breast cancer.

PMID- 21898664
TI  - A new algorithm to reduce noise in microscopy images implemented with a simple
      program in python.
AB  - All microscopical images contain noise, increasing when (e.g., transmission
      electron microscope or light microscope) approaching the resolution limit. Many
      methods are available to reduce noise. One of the most commonly used is image
      averaging. We propose here to use the mode of pixel values. Simple Python
      programs process a given number of images, recorded consecutively from the same
      subject. The programs calculate the mode of the pixel values in a given position
      (a, b). The result is a new image containing in (a, b) the mode of the values.
      Therefore, the final pixel value corresponds to that read in at least two of the
      pixels in position (a, b). The application of the program on a set of images
      obtained by applying salt and pepper noise and GIMP hurl noise with 10-90%
      standard deviation showed that the mode performs better than averaging with three
      eight images. The data suggest that the mode would be more efficient (in the
      sense of a lower number of recorded images to process to reduce noise below a
      given limit) for lower number of total noisy pixels and high standard deviation
      (as impulse noise and salt and pepper noise), while averaging would be more
      efficient when the number of varying pixels is high, and the standard deviation
      is low, as in many cases of Gaussian noise affected images. The two methods may
      be used serially.

PMID- 21898665
TI  - Scanning electron microscopy of antennal sensible of Anoplistes halodendri
      halodendri and Anoplistes halodendri ephippium (Coleoptera: Cerambycidae).
AB  - Anoplistes halodendri halodendri (Pallas, 1776) and Anoplistes halodendri
      ephippium (Stevens and Dalman, 1817) are two subspecies of the longicorn beetle
      A. halodendri (Coleoptera, Cerambycidae). In the recent years, these subspecies
      have been spreading rapidly in Hippophae rhamnoides and Hedysarum scoparium
      shrubberies in the Chinese provinces of Shanxi and Kingie, causing mass mortality
      of these shrubberies species and consequently leading to great damage to local
      ecological environment construction as well as high economic, ecological, and
      societal losses. To control their hazards effectively, here, we study and compare
      the types, densities, and distribution of antennal sensilla of A. h. halodendri
      and A. h. ephippium using scanning electron microscopy. Eight sensilla types were
      observed on the antennae of these two subspecies, including placoid sensilla
      (Ps), chaetica sensilla (ch) (types I-III), sensilla basiconica (b) (types I and
      II), sensilla gemmiformium (G), and auricillica sensilla (au). Ps predominated on
      the antennae of both A. h. halodendri and A. h. ephippium, followed by b and ch,
      and G and au. There were differences between the subspecies in the distribution
      and density of the different sensilla types, with ch I being found exclusively on
      the antennae of A. h. ephippium and b I and au on the antennae of A. h.
      halodendri only. With the exception of Ps, the densities of ch II, ch III, b II,
      and G on the antennae of A. h. halodendri were much higher than on the antennae
      of A. h. ephippium. These results provide sufficient evidence to clarify the
      receptive mechanisms used by these two subspecies of longicorn beetles and their
      responses to volatile semiochemicals released by their host plants as well as
      discuss their differences with respect to host and habitat selection.

PMID- 21898666
TI  - Morphological and morphometric characterization of agoutis' peripheral blood
      cells (Dasyprocta prymnolopha, Wagler, 1831) raised in captivity.
AB  - Thirty adult agoutis (Dasyprocta primnolopha) from the Nucleus of Study and
      Preservation of Wild Animals at the Federal University of Piaui were used. Blood
      scrubs of these animals were colored by the Leishman method and analyzed in light
      microscopy. The cells had been measured using programs that analyze images (Leica
      QWin - Image Processing and Analysis Software). Mature erythrocytes, basophil
      reticulocytes, lymphocytes, eosinophils, neutrophils, monocytes, and thrombocytes
      were identified. Agoutis' erythrocytes presented elliptical form, without nucleus
      with an average diameter of 5.64 micromeres +/- 0.38. The lymphocytes are
      spherical cells with scarce cytoplasm, dense and with a very centralized rounded
      nucleus measuring an average diameter of 13.20 micromeres +/- 0.35. The monocytes
      are slightly basophilic, with a spherical nucleus, central constriction, and an
      average diameter of 20.59 micromeres +/- 0.32. The neutrophils are spherical,
      with a polymorphic lobulated nucleus, with an average diameter of 11.2 micromeres
      +/- 0.20. The eosinophils are spherical with lobulated nucleus and with an
      average diameter of 14.25 micromeres +/- 0.36. Only five basophils were observed,
      with abundance of cytoplasmic granules with 9.8 micrometers of diameter +/- 0.30.
      Thrombocytopenic pleomorphism was frequent. There were similarities in the
      cellular constituents in peripheral blood of agoutis and of other rodents and
      humans. The cellular types from the peripheral blood, the morphology, and
      morphometry of the blood's cells did not vary according to sex.

PMID- 21898667
TI  - Gross anatomical and scanning electron microscopic studies of the oropharyngeal
      cavity in the European magpie (Pica pica) and the common raven (Corvus corax).
AB  - There is no descriptive information about morphology of the oropharyngeal cavity
      including tongue, palate, and laryngeal region in Corvidae family. This study not
      only presents the first definitive anatomical description of the structures in
      the oropharyngeal cavity of magpie and raven but also reviews and compares the
      scattered information on the morphology of the other avian species available in
      the literature. In this study, the organs of four birds (two magpies and two
      ravens) were used. The tongue in magpie and raven was considerably elongated and
      terminated with an oval-shaped apex. Although the lingual apex in the magpie was
      divided by fissure, no such bifurcation existed on that of raven. Lingual apex
      was quite distinctive in both species, and multiple acicular processes covered
      the apex. These occurrences on the tongue of magpie were replaced by thread-like
      processes as approaching the lingual body. In raven, these processes were mostly
      foliated, becoming longer toward the back of the lingua, and denser compared with
      raven. Moreover, we observed conical papillary crest, which was pointed backward
      and located between the lingual body and the radix of the tongue and pharyngeal
      conical papillae around the glottis and palate clefts in both species. There was
      a transversal fold separating the choanal cleft from the infundibular cleft in
      raven. Anatomy of the oropharyngeal cavity in the raven and magpie, which are the
      member of the same family, Corvidae, showed little differences and overall their
      oral morphological features were excessively similar.

PMID- 21898668
TI  - An automated approach for cerebral microvascularity labeling in microscopy
      images.
AB  - Morphological observation and analysis of cerebral microvascular network is an
      essential way to study cerebral function. Automated labeling of cerebral
      microvascular in microscopy images is one of the key steps for quantitative
      analysis of microvascular network in the specimens of brain mantle. It is
      presented in this work that an automated image processing approach based on
      curvilinear structure detector is applied to label and analyze the microvascular
      in the image. Steerable filter is also introduced to address the detecting
      confusion in branching regions. And then the vascular morphology analysis, such
      as average microvascular density, is also performed after image processing.
      Validation has demonstrated that the results from proposed approach are
      satisfied. The proposed method is finally applied in the study of cerebral
      microvascular dysfunction induced by gamma-ray irradiation.

PMID- 21898669
TI  - Application of analytical electron microscopic methods to investigate the
      function of spherites in the midgut of the larval antlion Euroleon nostras
      (Neuroptera: Myrmeleontidae).
AB  - This study presents an application of analytical electron microscopy in biology
      to investigate the chemical composition of the spherites and to elucidate the
      importance of these methods in the life sciences. The structure of the spherites
      in the midgut cells of first, second, and third instar larvae Euroleon nostras
      was investigated by a combination of transmission electron microscopy (TEM),
      energy dispersive X-ray spectroscopy (EDXS), electron energy-loss spectroscopy
      (EELS), and energy filtering TEM (EFTEM). The structure and chemical composition
      of the spherites changed during the metamorphosis. In first larvae, the spherites
      are composed of amorphous, flocculent material, containing C, N, and O. In second
      larvae and third ones, the spherites have concentric layers of alternating
      electron-dense and electron-lucent material. In second larvae, Si, P, Ca, and Fe
      are accumulated in the spherite organic matrix, composed of C, N, and O. In the
      spherites of third larvae, additionally Al was found. Therefore, the spherites
      are thought to store organic compounds in all three larval stages of E. nostras
      and additionally inorganic compounds in second and third ones. In first larvae,
      spherites are present in the midgut cells; in second and third larvae, they are
      present in the cells of the midgut and in its lumen. It could be suggested that
      the spherites might be involved in the regulation of the appropriate mineral
      composition of the internal environment and could serve as the accumulation site
      of nontoxic waste materials that cannot be metabolized.

PMID- 21898670
TI  - MRT letter: segmentation and texture-based classification of breast mammogram
      images.
AB  - Breast cancer is the most common cancer diagnosed among women. In this article,
      support vector machine is used to classify digital mammogram images into
      malignant and benign. Wiener filter is used to handle the possible quantum noise,
      which is more likely to occur in mammograms. Stack-based connected component
      method is proposed for background removal, and the image is enhanced using
      retinax method. Seeded region growing algorithm is used to remove the pectoral
      muscle part of the mammogram. We have extracted 13 different multidomains'
      features for classification. Results show the superiority of the proposed
      algorithm in terms of sensitivity, specificity, and accuracy. We have used MIAS
      database of mammography for experimentation.

PMID- 21898671
TI  - Immunohistochemical detection and quantification of T cells in the small
      intestine of Isospora suis-infected piglets--influence of fixation technique and
      intestinal segment.
AB  - Quantification of immunohistochemical results constitutes an important tool in
      the analysis of cells and tissue that is not readily replaced by other
      techniques. For reliable quantification, it is essential to consider factors such
      as tissue fixation and tissue sampling. We report a study on the model of the
      intestine of Isospora suis-infected piglets, in which we addressed (1) whether
      the quantity of detectable T cells in the intestinal mucosa is the same in
      formalin-, HOPE(r)-, and cryo-conserved material or whether the amounts of T
      cells at least correlate with one another; and (2) whether single jejunal
      segments differ in regard to the quantity of mucosal T cells and variability of
      lymphocyte infiltration. Quantification of T cells in histological sections of
      different parts of the jejunum of 15-22 day old piglets infected with I. suis was
      performed using an anti-CD3-antibody and stereological point counting. Area
      fractions of T-cell profiles per intestinal mucosa profile were higher in cryo
      conserved samples than in HOPE(r)- and formalin-conserved material but no
      correlation between different fixations could be found. The proximal part of the
      jejunum contained fewer T cells compared with mid- and end-jejunum. Coefficients
      of variation did not differ between the intestinal segments. For quantification
      of T cells in the gut mucosa of piglets infected with I. suis, the cryo-conserved
      mid jejunum seems most suitable in cases when unbiased sampling of the complete
      intestine is not feasible. It is generally not possible to compare quantitative
      results of immunostaining in samples conserved by different methods.

PMID- 21898672
TI  - Integrated motivational interviewing and cognitive-behavioural therapy for
      bipolar disorder with comorbid substance use.
AB  - Although comorbid substance use is a common problem in bipolar disorder, there
      has been little research into options for psychological therapy. Studies to date
      have concentrated on purely cognitive-behavioural approaches, which are not
      equipped to deal with the ambivalence to change exhibited by many towards therapy
      designed to change substance use. This paper provides the first report of an
      integrated psychological treatment approach for bipolar disorder with comorbid
      substance use. The intervention reported combines motivational interviewing and
      cognitive-behavioural therapy to address ambivalence and equips individuals with
      strategies to address substance use. Across five individual case studies,
      preliminary evidence is reported to support the acceptability and the feasibility
      of this approach. Despite most participants not highlighting their substance use
      as a primary therapy target, all but one exhibited reduced use of drugs or
      alcohol at the end of therapy, sustained at 6 months' follow-up. There was some
      evidence for improvements in mood symptoms and impulsiveness, but this was less
      clear-cut. The impact of social and relationship issues on therapy process and
      outcome is discussed. The implications of the current findings for future
      intervention research in this area are considered.

PMID- 21898673
TI  - Understanding the importance of attachment in shame traumatic memory relation to
      depression: the impact of emotion regulation processes.
AB  - BACKGROUND: Early relationships are crucial to human brain maturation, well
      being, affect regulation and self-other schema. Shame traumatic memories are
      related to psychopathology, and recent research has shown that the quality and
      type of attachment relationships may be crucial in shame traumatic memories in
      relation to psychopathology. The current study explores a mediator model of
      emotion regulation processes (rumination, thought suppression and dissociation)
      on the association between shame traumatic memory, with attachment figures and
      with others, and depressive symptoms. METHOD: Ninety subjects from the general
      community population completed the Shame Experiences Interview (SEI), assessing
      shame experiences from childhood and adolescence, and a battery of self-report
      scales measuring shame traumatic memory, rumination, thought suppression,
      dissociation and depression. RESULTS: Mediator analyses show that emotion
      regulation processes, such as brooding, thought suppression and dissociation,
      mediate the association between shame traumatic memory with others and
      depression. In contrast, shame traumatic memory with attachment figures has a
      direct effect on depression, not mediated by emotion regulation processes, with
      only brooding partially mediating this relation. CONCLUSION: The current findings
      shed light on the importance of attachment figures on the structuring of shame
      traumatic memories and on their impact on psychopathological symptoms, adding to
      recent neuroscience research and Gilbert's approach on shame and compassion. In
      addition, our results emphasize the relevance of addressing shame memories,
      mainly those that involve attachment figures, particularly when working with
      patients suffering from depressive symptoms and/or that find compassion difficult
      or scary. KEY PRACTITIONER MESSAGE: The quality of attachment relationships is
      important in how shame memories are structured and in their relation to
      psychopathology. The relationship between shame traumatic memory with attachment
      figures and depressive symptoms is not mediated by emotion regulation processes
      (rumination, thought suppression and dissociation). In contrast, these processes
      emerge as mediators on the association between shame traumatic memory with others
      and depression. For people suffering from depressive symptoms, having been shamed
      by an attachment figure may be a major block to develop self-compassion and
      receive compassion from others and may constitute an important obstacle to
      recovery. When working with patients suffering from depressive symptoms and/or
      that find compassion difficult or scary, it is important to target shame
      memories, especially those that involve attachment figures. In therapy with
      individuals with depressive symptoms and who reveal shame traumatic memories
      involving others, it may not only be pertinent to target these memories but also
      to evaluate and intervene on emotion regulation processes, particularly
      rumination, thought suppression and dissociation.

PMID- 21898674
TI  - Functional adaptive changes within the hippocampal memory system of patients with
      multiple sclerosis.
AB  - Memory deficits are highly prevalent in multiple sclerosis (MS). As the
      hippocampus is crucial to memory processing, a functional magnetic resonance
      imaging (fMRI) task was used to investigate changes in hippocampal function in MS
      patients with and without cognitive decline. Fifty patients with MS, (34
      cognitively preserved (CP) and 16 cognitively impaired (CI)) and 30 healthy
      controls completed an episodic memory fMRI task (encoding and retrieval) that was
      used to specifically activate the hippocampus. During encoding of correctly
      remembered items, increased brain activation was seen in the parahippocampal
      areas bilaterally and in the left anterior cingulate gyrus in the CP patients
      compared to the controls (unclustered, Z >= 3.1, P <= 0.001). No brain areas
      showed less activation. In CI patients the right (para)hippocampal areas and the
      prefrontal cortex showed less brain activation compared to controls (cluster
      corrected, P < 0.05). The posterior cingulate gyrus and the left precuneus showed
      increased activation in CI patients when compared to controls (unclustered Z >=
      3.1, P <= 0.001). No significant differences were found on structural MRI
      measures between the CP and CI patients. These results suggest the presence of
      functional adaptation in the memory network before cognitive decline becomes
      evident in MS, as displayed by the increased brain activation in the hippocampal
      cingulate memory system in CP patients. Interestingly, CI patients showed less
      activation in the hippocampal network during correct encoding. These findings are
      important for future cognitive therapeutic studies, since cognitive intervention
      might be most effective before cognitive impairment is present and when adaptive
      changes of the brain are most prominent.

PMID- 21898675
TI  - Robotic movement preferentially engages the action observation network.
AB  - As humans, we gather a wide range of information about other people from watching
      them move. A network of parietal, premotor, and occipitotemporal regions within
      the human brain, termed the action observation network (AON), has been implicated
      in understanding others' actions by means of an automatic matching process that
      links observed and performed actions. Current views of the AON assume a matching
      process biased towards familiar actions; specifically, those performed by
      conspecifics and present in the observer's motor repertoire. In this study, we
      test how this network responds to form and motion cues when observing natural
      human motion compared to rigid robotic-like motion across two independent
      functional neuroimaging experiments. In Experiment 1, we report the surprising
      finding that premotor, parietal, occipitotemporal regions respond more robustly
      to rigid, robot-like motion than natural human motion. In Experiment 2, we
      replicate and extend this finding by demonstrating that the same pattern of
      results emerges whether the agent is a human or a robot, which suggests the
      preferential response to robot-like motion is independent of the agent's form.
      These data challenge previous ideas about AON function by demonstrating that the
      core nodes of this network can be flexibly engaged by novel, unfamiliar actions
      performed by both human and non-human agents. As such, these findings suggest
      that the AON is sensitive to a broader range of action features beyond those that
      are simply familiar.

PMID- 21898676
TI  - Age-related vulnerabilities along the hippocampal longitudinal axis.
AB  - Evidence for an anterior-posterior gradient of age-related volume reduction along
      the hippocampal longitudinal axis has been reported in normal aging, but
      functional changes have yet to be systematically investigated. The current study
      applied an advanced brain mapping technique, large deformation diffeomorphic
      metric mapping (LDDMM), automatically delineating the hippocampus into the
      anterior and posterior segments based on anatomical landmarks. We studied this
      anterior-posterior gradient in terms of structural and functional MRI in 66
      participants aged from 19 to 79 years. The results showed age-related structural
      volume reduction in both anterior and posterior hippocampi, with greater tendency
      for anterior decrease. FMRI task contrasts that robustly activated the anterior
      (associative/relational processing) and posterior (novelty) hippocampus
      independently, showed only significant reduction of activation in the anterior
      hippocampus as age increased. Our results revealed positive correlation between
      structural atrophy and functional decrease in the anterior hippocampi, regardless
      of task performance in normal aging. These findings suggest that anatomy and
      functions related to the anterior hippocampus may be more vulnerable to aging,
      than previously thought.

PMID- 21898677
TI  - Brain structural trajectories over the adult lifespan.
AB  - The aim of this large-sample cross-sectional voxel-based morphometry (VBM) study
      of anatomical brain data was to investigate linear and nonlinear age-related
      trajectories of grey matter volume in the human brain during the adult lifespan.
      To date, there are only a few structural brain studies investigating local
      nonlinear aspects at the voxel level, i.e., without using anatomical ROIs as a
      priori hypothesis. Therefore, we analyzed 547 T1-weighted MR images of healthy
      adult brains with an age range of 19 to 86 years, including 161 scans of subjects
      with ages 60 and older. We found that the gray matter volume in some regions did
      not linearly decrease over time, but rather exhibited a delayed decline.
      Nonlinear age trajectories were observed in the medial temporal lobe regions, the
      basal ganglia, and parts of the cerebellum. Their trajectories indicated a
      preservation of grey matter volume during the early adult lifespan.
      Interestingly, we found nonlinear grey matter structural dynamics specifically in
      parts of the brain that have been extensively discussed in the context of
      learning and memory. We propose a hypothesis in relation to the functional role
      of these brain regions that may explain these results.

PMID- 21898678
TI  - Brain regions that process case: evidence from Basque.
AB  - The aim of this event-related fMRI study was to investigate the cortical networks
      involved in case processing, an operation that is crucial to language
      comprehension yet whose neural underpinnings are not well-understood. What is the
      relationship of these networks to those that serve other aspects of syntactic and
      semantic processing? Participants read Basque sentences that contained case
      violations, number agreement violations or semantic anomalies, or that were both
      syntactically and semantically correct. Case violations elicited activity
      increases, compared to correct control sentences, in a set of parietal regions
      including the posterior cingulate, the precuneus, and the left and right inferior
      parietal lobules. Number agreement violations also elicited activity increases in
      left and right inferior parietal regions, and additional activations in the left
      and right middle frontal gyrus. Regions-of-interest analyses showed that almost
      all of the clusters that were responsive to case or number agreement violations
      did not differentiate between these two. In contrast, the left and right anterior
      inferior frontal gyrus and the dorsomedial prefrontal cortex were only sensitive
      to semantic violations. Our results suggest that whereas syntactic and semantic
      anomalies clearly recruit distinct neural circuits, case, and number violations
      recruit largely overlapping neural circuits and that the distinction between the
      two rests on the relative contributions of parietal and prefrontal regions,
      respectively. Furthermore, our results are consistent with recently reported
      contributions of bilateral parietal and dorsolateral brain regions to syntactic
      processing, pointing towards potential extensions of current neurocognitive
      theories of language.

PMID- 21898679
TI  - Assessment of cortical degeneration in patients with Parkinson's disease by voxel
      based morphometry, cortical folding, and cortical thickness.
AB  - Noninvasive brain imaging methods provide useful information on cerebral
      involution and degenerative processes. Here we assessed cortical degeneration in
      20 nondemented patients with Parkinson's disease (PD) and 20 healthy controls
      using three quantitative neuroanatomical approaches: voxel-based morphometry
      (VBM), cortical folding (BrainVisa), and cortical thickness (FreeSurfer). We
      examined the relationship between global and regional gray matter (GM) volumes,
      sulcal indices, and thickness measures derived from the previous methods as well
      as their association with cognitive performance, age, severity of motor symptoms,
      and disease stage. VBM analyses showed GM volume reductions in the left temporal
      gyrus in patients compared with controls. Cortical folding measures revealed
      significant decreases in the left frontal and right collateral sulci in patients.
      Finally, analysis of cortical thickness showed widespread cortical thinning in
      right lateral occipital, parietal and left temporal, frontal, and premotor
      regions. We found that, in patients, all global anatomical measures correlated
      with age, while GM volume and cortical thickness significantly correlated with
      disease stage. In controls, a significant association was found between global GM
      volume and cortical folding with age. Overall these results suggest that the
      three different methods provide complementary and related information on
      neurodegenerative changes occurring in PD, however, surface-based measures of
      cortical folding and especially cortical thickness seem to be more sensitive than
      VBM to identify regional GM changes associated to PD.

PMID- 21898680
TI  - Pretreatment with interferon-gamma enhances the therapeutic activity of
      mesenchymal stromal cells in animal models of colitis.
AB  - Mesenchymal stromal cells (MSCs) are currently under investigation for the
      treatment of inflammatory disorders, including Crohn's disease. MSCs are
      pluripotent cells with immunosuppressive properties. Recent data suggest that
      resting MSCs do not have significant immunomodulatory activity, but that the
      immunosuppressive function of MSCs has to be elicited by interferon-gamma (IFN
      gamma). In this article, we assessed the effects of IFN-gamma prestimulation of
      MSCs (IMSCs) on their immunosuppressive properties in vitro and in vivo. To this
      end, we pretreated MSCs with IFN-gamma and assessed their therapeutic effects in
      dextran sodium sulfate (DSS)- and trinitrobenzene sulfonate (TNBS)-induced
      colitis in mice. We found that mice treated with IMSCs (but not MSCs) showed a
      significantly attenuated development of DSS-induced colitis. Furthermore, IMSCs
      alleviated symptoms of TNBS-induced colitis. IMSC-treated mice displayed an
      increase in body weight, lower colitis scores, and better survival rates compared
      with untreated mice. In addition, serum amyloid A protein levels and local
      proinflammatory cytokine levels in colonic tissues were significantly suppressed
      after administration of IMSC. We also observed that IMSCs showed greater
      migration potential than unstimulated MSCs to sites within the inflamed
      intestine. In conclusion, we show that prestimulation of MSCs with IFN-gamma
      enhances their capacity to inhibit Th1 inflammatory responses, resulting in
      diminished mucosal damage in experimental colitis. These data demonstrate that
      IFN-gamma activation of MSCs increases their immunosuppresive capacities and
      importantly, their therapeutic efficacy in vivo.

PMID- 21898681
TI  - Distinct developmental ground states of epiblast stem cell lines determine
      different pluripotency features.
AB  - Epiblast stem cells (EpiSCs) are pluripotent stem cells derived from mouse
      postimplantation embryos at embryonic day (E) 5.5-E7.5 at the onset of
      gastrulation, which makes them a valuable tool for studying mammalian
      postimplantation development in vitro. EpiSCs can also be reprogrammed into a
      mouse embryonic stem cell (mESC)-like state. Some reports have shown that the
      reversion of EpiSCs requires transcription factor overexpression, whereas others
      have suggested that use of stringent mESC culture conditions alone is sufficient
      for the reversion of EpiSCs. To clarify these discrepancies, we systematically
      compared a panel of independent EpiSC lines. We found that--regardless of the
      embryonic day of derivation--the different EpiSC lines shared a number of
      defining characteristics such as the ability to form teratomas. However, despite
      use of standard EpiSC culture conditions, some lines exhibited elevated
      expression of genes associated with mesendodermal differentiation. Pluripotency
      (Oct4) and mesodermal (Brachyury) marker genes were coexpressed in this subset of
      lines. Interestingly, the expression of mesendodermal marker genes was negatively
      correlated with the cells' ability to efficiently undergo neural induction.
      Moreover, these mesodermal marker gene-expressing cell lines could not be
      efficiently reverted to an mESC-like state by using stringent mESC culture
      conditions. Conversely, Brachyury overexpression diminished the reversion
      efficiency in otherwise Brachyury-negative lines. Overall, our data suggest that
      different EpiSC lines may undergo self-renewal into distinct developmental
      states, a finding with important implications for functional readouts such as
      reversion of EpiSCs to an mESC-like state as well as directed differentiation.

PMID- 21898682
TI  - A novel role for an RNA polymerase III subunit POLR3G in regulating pluripotency
      in human embryonic stem cells.
AB  - The pluripotency of human embryonic stem cells (hESC) could have great potential
      for the development of cell replacement therapies. Previous studies have
      converged on the finding that OCT4, SOX2, and NANOG serve as key regulators in
      the maintenance of hESC. However, other signals that regulate hESC maintenance
      remain poorly studied. Here we describe a novel role of an RNA polymerase III
      (Pol III) subunit, POLR3G, in the maintenance of pluripotency in hESC. We
      demonstrate the presence of POLR3G in undifferentiated hESC, human induced
      pluripotent stem cells (hiPSC), and early mouse blastocysts. Downregulation of
      POLR3G is observed on differentiation of hESC and hiPSC, suggesting that POLR3G
      can be used as a molecular marker to readily identify undifferentiated
      pluripotent stem cells from their differentiated derivatives. Using an inducible
      shRNA lentiviral system, we found evidence that decreased levels of POLR3G result
      in loss of pluripotency and promote differentiation of hESC to all three germ
      layers but have no effect on cell apoptosis. On the other hand, overexpression of
      POLR3G has no effect on pluripotency and apoptosis in undifferentiated hESC.
      Interestingly, hESC expressing elevated levels of POLR3G are more resistant to
      differentiation. Furthermore, our experimental results show that POLR3G is a
      downstream target of OCT4 and NANOG, and our pharmacological study indicated that
      POLR3G expression can be readily regulated by the Erk1/2 signaling pathway. This
      study is the first to show an important role of POLR3G in the maintenance of
      hESC, suggesting a potential role of Pol III transcription in regulating hESC
      pluripotency.

PMID- 21898683
TI  - Concise review: managing genotoxicity in the therapeutic modification of stem
      cells.
AB  - The therapeutic use of procedures for genetic stem cell modification is limited
      by potential adverse events related to uncontrolled mutagenesis. Prominent
      findings have been made in hematopoietic gene therapy, demonstrating the risk of
      clonal, potentially malignant outgrowth on the basis of mutations acquired during
      or after therapeutic genome modification. The incidence and the growth rate of
      insertional mutants have been linked to the "stemness" of the target cells and
      vector-related features such as the integration pattern, the architecture, and
      the exact content of transgene cassettes. Milieu factors supporting the survival
      and expansion of mutants may eventually allow oncogenic progression. Similar
      concerns apply for medicinal products based on pluripotent stem cells. Focusing
      on the genetic stress induced by insertional mutagenesis and culture adaptation,
      we propose four conclusions. (a) Mutations occurring in the production of stem
      cell-based medicines may be unavoidable and need to be classified according to
      their risk to trigger the formation of clones that are sufficiently long-lived
      and mitotically active to acquire secondary transforming mutations. (b) The
      development of rational prevention strategies depends upon the identification of
      the specific mutations forming such "dominant clones" (which can also be
      addressed as cancer stem cell precursors) and a better knowledge of the
      mechanisms underlying their creation, expansion, and homeostatic control. (c)
      Quantitative assay systems are required to assess the practical value of
      preventive actions. (d) Improved approaches for the genetic modification of stem
      cells can address all critical steps in the origin and growth control of mutants.

PMID- 21898684
TI  - Discovery of nonsteroidal anti-inflammatory drug and anticancer drug enhancing
      reprogramming and induced pluripotent stem cell generation.
AB  - Recent breakthroughs in creating induced pluripotent stem cells (iPSCs) provide
      alternative means to obtain embryonic stem-like cells without destroying embryos
      by introducing four reprogramming factors (Oct3/4, Sox2, and Klf4/c-Myc or
      Nanog/Lin28) into somatic cells. iPSCs are versatile tools for investigating
      early developmental processes and could become sources of tissues or cells for
      regenerative therapies. Here, for the first time, we describe a strategy to
      analyze genomics datasets of mouse embryonic fibroblasts (MEFs) and embryonic
      stem cells to identify genes constituting barriers to iPSC reprogramming. We
      further show that computational chemical biology combined with genomics analysis
      can be used to identify small molecules regulating reprogramming. Specific
      downregulation by small interfering RNAs (siRNAs) of several key MEF-specific
      genes encoding proteins with catalytic or regulatory functions, including WISP1,
      PRRX1, HMGA2, NFIX, PRKG2, COX2, and TGFbeta3, greatly increased reprogramming
      efficiency. Based on this rationale, we screened only 17 small molecules in
      reprogramming assays and discovered that the nonsteroidal anti-inflammatory drug
      Nabumetone and the anticancer drug 4-hydroxytamoxifen can generate iPSCs without
      Sox2. Nabumetone could also produce iPSCs in the absence of c-Myc or Sox2 without
      compromising self-renewal and pluripotency of derived iPSCs. In summary, we
      report a new concept of combining genomics and computational chemical biology to
      identify new drugs useful for iPSC generation. This hypothesis-driven approach
      provides an alternative to shot-gun screening and accelerates understanding of
      molecular mechanisms underlying iPSC induction.

PMID- 21898685
TI  - In situ genetic correction of the sickle cell anemia mutation in human induced
      pluripotent stem cells using engineered zinc finger nucleases.
AB  - The combination of induced pluripotent stem cell (iPSC) technology and targeted
      gene modification by homologous recombination (HR) represents a promising new
      approach to generate genetically corrected, patient-derived cells that could be
      used for autologous transplantation therapies. This strategy has several
      potential advantages over conventional gene therapy including eliminating the
      need for immunosuppression, avoiding the risk of insertional mutagenesis by
      therapeutic vectors, and maintaining expression of the corrected gene by
      endogenous control elements rather than a constitutive promoter. However, gene
      targeting in human pluripotent cells has remained challenging and inefficient.
      Recently, engineered zinc finger nucleases (ZFNs) have been shown to
      substantially increase HR frequencies in human iPSCs, raising the prospect of
      using this technology to correct disease causing mutations. Here, we describe the
      generation of iPSC lines from sickle cell anemia patients and in situ correction
      of the disease causing mutation using three ZFN pairs made by the publicly
      available oligomerized pool engineering method (OPEN). Gene-corrected cells
      retained full pluripotency and a normal karyotype following removal of
      reprogramming factor and drug-resistance genes. By testing various conditions, we
      also demonstrated that HR events in human iPSCs can occur as far as 82 bps from a
      ZFN-induced break. Our approach delineates a roadmap for using ZFNs made by an
      open-source method to achieve efficient, transgene-free correction of monogenic
      disease mutations in patient-derived iPSCs. Our results provide an important
      proof of principle that ZFNs can be used to produce gene-corrected human iPSCs
      that could be used for therapeutic applications.

PMID- 21898686
TI  - Novel hematopoietic progenitor populations revealed by direct assessment of GATA1
      protein expression and cMPL signaling events.
AB  - Hematopoietic stem cells (HSCs) must exhibit tight regulation of both self
      renewal and differentiation to maintain homeostasis of the hematopoietic system
      as well as to avoid aberrations in growth that may result in leukemias or other
      disorders. In this study, we sought to understand the molecular basis of lineage
      determination, with particular focus on factors that influence
      megakaryocyte/erythrocyte-lineage commitment, in hematopoietic stem and
      progenitor cells. We used intracellular flow cytometry to identify two novel
      hematopoietic progenitor populations within the mouse bone-marrow cKit(+) Lineage
      (-) Sca1(+) (KLS) Flk2 (+) compartment that differ in their protein-level
      expression of GATA1, a critical megakaryocyte/erythrocyte-promoting transcription
      factor. GATA1-high repopulating cells exhibited the cell surface phenotype KLS
      Flk2(+ to int), CD150(int), CD105(+), cMPL(+), and were termed "FSE cells." GATA1
      low progenitors were identified as KLS Flk2(+), CD150(-), and cMPL(-), and were
      termed "Flk(+) CD150(-) cells." FSE cells had increased megakaryocyte/platelet
      potential in culture and transplant settings and exhibited a higher clonal
      frequency of colony-forming unit-spleen activity compared with Flk(+) CD150(-)
      cells, suggesting functional consequences of GATA1 upregulation in promoting
      megakaryocyte and erythroid lineage priming. Activation of ERK and AKT signal
      transduction cascades was observed by intracellular flow cytometry in long-term
      HSCs and FSE cells, but not in Flk(+) CD150(-) cells in response to stimulation
      with thrombopoietin, an important megakaryocyte-promoting cytokine. We provide a
      mechanistic rationale for megakaryocyte/erythroid bias within KLS Flk2(+) cells,
      and demonstrate how assessment of intracellular factors and signaling events can
      be used to refine our understanding of lineage commitment during early definitive
      hematopoiesis.

PMID- 21898688
TI  - Low level of c-kit expression marks deeply quiescent murine hematopoietic stem
      cells.
AB  - Although c-kit is expressed highly on murine hematopoietic stem cells (HSCs) and
      essential for bone marrow (BM) hematopoiesis, the significance of the high level
      of expression of c-kit on HSCs was not well determined. We show here that
      CD150(+) CD48(-) Lineage(-) Sca-1(+) c-kit(+) HSCs in adult BM are distributed
      within the range of roughly a 20-fold difference in the expression level of c
      kit, and that c-kit density correlates with the cycling status of the HSC
      population. This predisposition is more evident in the BM of mice older than 30
      weeks. The HSCs in G(0) phase express a lower level of c-kit both on the cell
      surface and inside the cells, which cannot be explained by ligand receptor
      binding and internalization. It is more likely that the low level of c-kit
      expression is a unique property of HSCs in G(0). Despite functional differences
      in the c-kit gradient, the HSCs are uniformly hypoxic and accessible to blood
      perfusion. Therefore, our data indicate the possibility that the hypoxic state of
      the HSCs is actively regulated, rather than them being passively hypoxic through
      a simple anatomical isolation from the circulation.

PMID- 21898687
TI  - Effects on proliferation and differentiation of multipotent bone marrow stromal
      cells engineered to express growth factors for combined cell and gene therapy.
AB  - A key mechanism for mesenchymal stem cells/bone marrow stromal cells (MSCs) to
      promote tissue repair is by secretion of soluble growth factors (GFs). Therefore,
      clinical application could be optimized by a combination of cell and gene
      therapies, where MSCs are genetically modified to express higher levels of a
      specific factor. However, it remains unknown how this overexpression may alter
      the fate of the MSCs. Here, we show effects of overexpressing the growth factors,
      such as basic fibroblast growth factor (bFGF), platelet derived growth factor B
      (PDGF-BB), transforming growth factor beta(1) (TGF-beta(1) ), and vascular
      endothelial growth factor (VEGF), in human bone marrow-derived MSCs. Ectopic
      expression of bFGF or PDGF-B lead to highly proliferating MSCs and lead to a
      robust increase in osteogenesis. In contrast, adipogenesis was strongly inhibited
      in MSCs overexpressing PDGF-B and only mildly affected in MSCs overexpressing
      bFGF. Overexpression of TGF-beta(1) blocked both osteogenic and adipogenic
      differentiation while inducing the formation of stress fibers and increasing the
      expression of the smooth muscle marker calponin-1 and the chondrogenic marker
      collagen type II. In contrast, MSCs overexpressing VEGF did not vary from control
      MSCs in any parameters, likely due to the lack of VEGF receptor expression on
      MSCs. MSCs engineered to overexpress VEGF strongly induced the migration of
      endothelial cells and enhanced blood flow restoration in a xenograft model of
      hind limb ischemia. These data support the rationale for genetically modifying
      MSCs to enhance their therapeutically relevant trophic signals, when safety and
      efficacy can be demonstrated, and when it can be shown that there are no unwanted
      effects on their proliferation and differentiation.

PMID- 21898689
TI  - Core binding factor beta functions in the maintenance of stem cells and
      orchestrates continuous proliferation and differentiation in mouse incisors.
AB  - Rodent incisors grow continuously throughout life, and epithelial progenitor
      cells are supplied from stem cells in the cervical loop. We report that
      epithelial Runx genes are involved in the maintenance of epithelial stem cells
      and their subsequent continuous differentiation and therefore growth of the
      incisors. Core binding factor beta (Cbfb) acts as a binding partner for all Runx
      proteins, and targeted inactivation of this molecule abrogates the activity of
      all Runx complexes. Mice deficient in epithelial Cbfb produce short incisors and
      display marked underdevelopment of the cervical loop and suppressed epithelial
      Fgf9 expression and mesenchymal Fgf3 and Fgf10 expression in the cervical loop.
      In culture, FGF9 protein rescues these phenotypes. These findings indicate that
      epithelial Runx functions to maintain epithelial stem cells and that Fgf9 may be
      a target gene of Runx signaling. Cbfb mutants also lack enamel formation and
      display downregulated Shh mRNA expression in cells differentiating into
      ameloblasts. Furthermore, Fgf9 deficiency results in a proximal shift of the Shh
      expressing cell population and ectopic FGF9 protein suppresses Shh expression.
      These findings indicate that Shh as well as Fgf9 expression is maintained by
      Runx/Cbfb but that Fgf9 antagonizes Shh expression. The present results provide
      the first genetic evidence that Runx/Cbfb genes function in the maintenance of
      stem cells in developing incisors by activating Fgf signaling loops between the
      epithelium and mesenchyme. In addition, Runx genes also orchestrate continuous
      proliferation and differentiation by maintaining the expression of Fgf9 and Shh
      mRNA.

PMID- 21898690
TI  - TAp63 is important for cardiac differentiation of embryonic stem cells and heart
      development.
AB  - p63, a member of the p53 family, is essential for skin morphogenesis and
      epithelial stem cell maintenance. Here, we report an unexpected role of TAp63 in
      cardiogenesis. p63 null mice exhibit severe defects in embryonic cardiac
      development, including dilation of both ventricles, a defect in trabeculation and
      abnormal septation. This was accompanied by myofibrillar disarray, mitochondrial
      disorganization, and reduction in spontaneous calcium spikes. By the use of
      embryonic stem cells (ESCs), we show that TAp63 deficiency prevents expression of
      pivotal cardiac genes and production of cardiomyocytes. TAp63 is expressed by
      endodermal cells. Coculture of p63-knockdown ESCs with wild-type ESCs,
      supplementation with Activin A, or overexpression of GATA-6 rescue cardiogenesis.
      Therefore, TAp63 acts in a non-cell-autonomous manner by modulating expression of
      endodermal factors. Our findings uncover a critical role for p63 in cardiogenesis
      that could be related to human heart disease.

PMID- 21898691
TI  - Systemic delivery of bone marrow-derived mesenchymal stromal cells diminishes
      neuropathology in a mouse model of Krabbe's disease.
AB  - In Krabbe's disease, a demyelinating disorder, add-on strategies targeting the
      peripheral nervous system (PNS) are needed, as it is not corrected by bone-marrow
      (BM) transplantation. To circumvent this limitation of BM transplantation, we
      assessed whether i.v. delivery of immortalized EGFP(+) BM-derived murine
      mesenchymal stromal cells (BM-MSC(TERT-EGFP) ) targets the PNS of a Krabbe's
      disease model, the Twitcher mouse. In vitro, BM-MSC(TERT-EGFP) retained the
      phenotype of primary BM-MSC and did not originate tumors upon transplantation in
      nude mice. In vivo, undifferentiated EGFP(+) cells grafted the Twitcher sciatic
      nerve where an increase in Schwann cell precursors and axonal number was
      detected. The same effect was observed on BM-MSC(TERT-EGFP) i.v. delivery
      following sciatic nerve crush, a model of axonal regeneration. Reiterating the in
      vivo findings, in a coculture system, BM-MSC(TERT-EGFP) induced the proliferation
      of Twitcher-derived Schwann cells and the neurite outgrowth of both Twitcher
      derived neurons and wild-type neurons grown in the presence of psychosine, the
      toxic substrate that accumulates in Krabbe's disease. In vitro, this neuritogenic
      effect was blocked by K252a, an antagonist of Trk receptors, and by antibody
      blockage of brain derived neurotrophic factor, a neurotrophin secreted by BM
      MSC(TERT-EGFP) and induced in neighboring Schwann cells. In vivo, BM-MSC(TERT
      EGFP) surmounted the effect of K252a, indicating their ability to act through a
      neurotrophin-independent mechanism. In summary, i.v. delivery of BM-MSC(TERT
      EGFP) exerts a multilevel effect targeting neurons and Schwann cells,
      coordinately diminishing neuropathology. Therefore, to specifically target the
      PNS, MSC should be considered an add-on option to BM transplantation in Krabbe's
      disease and in other disorders where peripheral axonal loss occurs.

PMID- 21898692
TI  - Concise review: Anemia caused by viruses.
AB  - Most of the viruses known to be associated with anemia in human tend to
      persistently infect their host and are noncytopathic or poorly cytopathic for
      blood cell progenitors. Infections with Epstein-Barr virus, cytomegalovirus,
      varicella-zoster virus, human herpes virus 6 (HHV-6), B19 parvovirus, human
      immunodeficiency virus, hepatitis A and C viruses and the putative viral agent
      associated with non-A-G post-hepatitis aplastic anemia have been reported in
      association with anemia. Nevertheless, a direct cytotoxic effect on erythroid
      progenitors has been clearly demonstrated only for human parvovirus B19 and
      evocated for HHV-6. A major role for destructive immunity is strongly suspected
      in the pathogenesis of anemia associated with the other viral infections. Host
      genes play a role in the occurrence of virus-induced anemia in animal models, and
      there are some evidences that genetic background could also influence the
      occurrence of virus-associated anemia in human.

PMID- 21898693
TI  - A microRNA-based system for selecting and maintaining the pluripotent state in
      human induced pluripotent stem cells.
AB  - Induced pluripotent stem cell (iPSC) technology has provided researchers with a
      unique tool to derive disease-specific stem cells for the study and possible
      treatment of degenerative disorders with autologous cells. The low efficiency and
      heterogeneous nature of reprogramming is a major impediment to the generation of
      personalized iPSC lines. Here, we report the generation of a lentiviral system
      based on a microRNA-regulated transgene that enables for the efficient selection
      of mouse and human pluripotent cells. This system relies on the differential
      expression pattern of the mature form of microRNA let7a in pluripotent versus
      committed or differentiated cells. We generated microRNA responsive green
      fluorescent protein and Neo reporters for specific labeling and active selection
      of the pluripotent cells in any culture condition. We used this system to
      establish Rett syndrome and Parkinson's disease human iPSCs. The presented
      selection procedure represents a straightforward and powerful tool for
      facilitating the derivation of patient-specific iPSCs.

PMID- 21898694
TI  - Concise review: Induced pluripotent stem cell-derived mesenchymal stem cells:
      progress toward safe clinical products.
AB  - Adult stem cell therapies have provided success for more than 50 years, through
      reconstitution of the hematopoietic system using bone marrow, umbilical cord
      blood, and mobilized peripheral blood transplantation. Mesenchymal stem cell
      (MSC)-mediated therapy is a fast-growing field that has proven safe and effective
      in the treatment of various degenerative diseases and tissue injuries. Since the
      first derivation of embryonic stem cells (ESCs) and induced pluripotent stem
      cells (iPSCs), there has been impressive progress toward developing safe clinical
      applications from PSCs. Recent successes in transgene-free iPSC reprogramming
      have brought attention to the potential of clinical applications of these
      pluripotent cells, but key hurdles must be overcome, which are discussed in this
      review. Looking to the future, it could be advantageous to derive MSC from iPSC
      or human ESC in cases where genetic engineering is needed, since in the PSCs,
      clones with "safe harbor" vector integration could be selected, expanded, and
      differentiated. Here, we describe the status of the progress of the use of MSC
      and PSCs in clinical trials and analyze the challenges that should be overcome
      before iPSC-derived MSC therapy can be used widely in the clinic.

PMID- 21898695
TI  - MiR-17 modulates osteogenic differentiation through a coherent feed-forward loop
      in mesenchymal stem cells isolated from periodontal ligaments of patients with
      periodontitis.
AB  - Chronic inflammatory diseases, such as rheumatoid arthritis and periodontitis,
      are the most common causes of bone tissue destruction. Recently, human
      periodontal ligament tissue-derived mesenchymal stem cells (PDLSCs), a population
      of multipotent stem cells, have been used to reconstruct tissues destroyed by
      chronic inflammation. However, the impact of the local inflammatory
      microenvironment on tissue-specific stem cells and the mechanisms controlling the
      effects of the local inflammatory environment remain poorly understood. In this
      study, we found that the multidifferentiation potential of mesenchymal stem cells
      (MSCs) isolated from periodontitis-affected periodontal ligament tissue (P
      PDLSCs) was significantly lower than that of MSCs isolated from healthy human
      periodontal ligament tissue (H-PDLSCs). Inflammation in the microenvironment
      resulted in an inhibition of miR-17 levels, and a perturbation in the expression
      of miR-17 partly reversed the differentiation potential of PDLSCs in this
      microenvironment. Furthermore, inflammation in the microenvironment promoted the
      expression of Smad ubiquitin regulatory factor one (Smurf1), an important
      negative regulator of MSC osteogenic differentiation. Western blotting and 3'
      untranslated regions (3'-UTR) reporter assays confirmed that Smurf1 is a direct
      target of miR-17 in PDLSCs. Our data demonstrate that excessive inflammatory
      cytokine levels, miR-17, and Smurf1 were all involved in a coherent feed-forward
      loop. In this circuit, inflammatory cytokines led to direct activation of Smurf1
      and downregulation of miR-17, thereby increasing degradation of Smurf1-mediated
      osteoblast-specific factors. The elucidation of the molecular mechanisms
      governing MSC osteogenic differentiation in a chronic inflammatory
      microenvironment could provide us with a better knowledge of chronic inflammatory
      disorder and improve stem cell-mediated inflammatory bone disease therapy.

PMID- 21898696
TI  - Neural stem cells, a step closer to clinic?

PMID- 21898697
TI  - Site-specific recombinase strategy to create induced pluripotent stem cells
      efficiently with plasmid DNA.
AB  - Induced pluripotent stem cells (iPSCs) have revolutionized the stem cell field.
      iPSCs are most often produced by using retroviruses. However, the resulting cells
      may be ill-suited for clinical applications. Many alternative strategies to make
      iPSCs have been developed, but the nonintegrating strategies tend to be
      inefficient, while the integrating strategies involve random integration. Here,
      we report a facile strategy to create murine iPSCs that uses plasmid DNA and
      single transfection with sequence-specific recombinases. PhiC31 integrase was
      used to insert the reprogramming cassette into the genome, producing iPSCs. Cre
      recombinase was then used for excision of the reprogramming genes. The iPSCs were
      demonstrated to be pluripotent by in vitro and in vivo criteria, both before and
      after excision of the reprogramming cassette. This strategy is comparable with
      retroviral approaches in efficiency, but is nonhazardous for the user, simple to
      perform, and results in nonrandom integration of a reprogramming cassette that
      can be readily deleted. We demonstrated the efficiency of this reprogramming and
      excision strategy in two accessible cell types, fibroblasts and adipose stem
      cells. This simple strategy produces pluripotent stem cells that have the
      potential to be used in a clinical setting.

PMID- 21898698
TI  - Gene expression profiling of neural stem cells and identification of regulators
      of neural differentiation during cortical development.
AB  - During mammalian brain development, neural stem cells transform from
      neuroepithelial cells to radial glial cells and finally remain as astrocyte-like
      cells in the postnatal and adult brain. Neuroepithelial cells divide
      symmetrically and expand the neural stem cell pool; after the onset of
      neurogenesis, radial glial cells sequentially produce deep layer neurons and then
      superficial layer neurons by asymmetric, self-renewing divisions during cortical
      development. Thereafter, gliogenesis supersedes neurogenesis, while a subset of
      neural stem cells retain their stemness and lurk in the postnatal and adult
      brain. Thus, neural stem cells undergo alterations in morphology and the capacity
      to proliferate or give rise to various types of neural cells in a temporally
      regulated manner. To shed light on the temporal alterations of embryonic neural
      stem cells, we sorted the green fluorescent protein-positive cells from the
      dorsolateral telencephalon (neocortical region) of pHes1-d2EGFP transgenic mouse
      embryos at different developmental stages and performed gene expression
      profiling. Among dozens of transcription factors differentially expressed by
      cells in the ventricular zone during the course of development, several of them
      exhibited the activity to inhibit neuronal differentiation when overexpressed.
      Furthermore, knockdown of Tcf3 or Klf15 led to accelerated neuronal
      differentiation of neural stem cells in the developing cortex, and neurospheres
      originated from Klf15 knockdown cells mostly lacked neurogenic activities and
      only retained gliogenic activities. These results suggest that Tcf3 and Klf15
      play critical roles in the maintenance of neural stem cells at early and late
      embryonic stages, respectively.

PMID- 21898700
TI  - Symptoms of eating disorders, drive for muscularity and physical activity among
      Norwegian adolescents.
AB  - PURPOSE: The aim of this study was to examine symptoms of eating disorders (ED),
      drive for muscularity and physical activity in a Norwegian adolescent population.
      METHODS: A total of 722 adolescents aged 12-18 years (response rate: 83%) filled
      out a questionnaire containing the Drive for Muscularity Scale, Eating Disorders
      Inventory subscales Drive for Thinness (EDI-DT), Body Dissatisfaction (EDI-BD)
      and Bulimia (EDI-B), and questions about amount of and motives for physical
      activity. RESULTS: Eating Disorders Inventory subscale scores were higher, and
      Drive for Muscularity Scale Score (DMS) scores were lower among girls compared
      with boys. EDI and DMS were correlated with motives for, but not amount of,
      physical activity. EDI and DMS were associated in boys, not girls. DISCUSSION:
      The associations between EDI and DMS among boys call for a wider approach when
      examining ED among boys.

PMID- 21898699
TI  - Mechanically induced focal adhesion assembly amplifies anti-adipogenic pathways
      in mesenchymal stem cells.
AB  - The fate of pluripotent mesenchymal stem cells (MSC) is determined through
      integration of chemical, spatial, and physical signals. The suppression of MSC
      adipogenesis by mechanical stimuli, which requires Akt-induced inhibition of
      glycogen synthase kinase 3beta (GSK3beta) with beta-catenin activation, can be
      enhanced by repetitive dosing within a single day. Here, we demonstrate that
      reapplication of cyclic strain within a 24-hour period leads to amplification of
      both Akt activation and its subsequent inhibition of GSK3beta, such that total
      cycle number can be reduced while still inhibiting adipogenesis. Amplification of
      Akt signaling is facilitated by a dynamic restructuring of the cell in response
      to mechanical signals, as evidenced by a transient increase in focal adhesion
      (FA) number and increased RhoA activity. Preventing FA assembly or development of
      tension blocks activation of Akt by mechanical signals, but not by insulin. This
      indicates that the FA infrastructure is essential to the physical, but not
      necessarily the chemical, sensitivity, and responsiveness of the cell. Exploiting
      the transient nature of cytoskeletal remodeling may represent a process to
      enhance cell responsiveness to mechanical input and ultimately define the fate of
      MSCs with a minimal input.

PMID- 21898701
TI  - Quantification of low expressed SCD1 gene in colonic mucosa from patients with
      active ulcerative colitis.

PMID- 21898702
TI  - Elevated serum IgE prior to acute severe infusion reaction during infliximab
      maintenance therapy in a Crohn's disease patient.

PMID- 21898703
TI  - Obsessions in normality and psychopathology.
AB  - BACKGROUND: This study examines the presence of obsessions in the general
      population and in various psychiatric disorders. Second, the impact of obsessions
      is studied in terms of general functioning and quality of life in the general
      population. METHODS: Data were derived from the Netherlands Mental Health Survey
      and Incidence Study (NEMESIS), a large representative sample of the Dutch
      population (n = 7,076). Diagnostic criteria were assessed by the Composite
      International Diagnostic Interview (CIDI). The association of quality of life and
      obsessions on each subject was assessed by using Short Form 36 Health Survey (SF
      36) and General Health Questionnaire (GHQ). RESULTS: Obsessions occurred
      frequently in the general population: the lifetime prevalence of obsessions was
      5.3% and the 12-month prevalence was 1.7%. Subjects with obsessions scored
      significantly worse (P<.0001) on all eight dimensions of the SF-36 as well as on
      the GHQ. When controlling for the presence of any mental disorder, the negative
      association of obsessions and low general health and well-being remained
      significantly intact. In patients with a psychiatric disorder, obsessions had a
      lifetime prevalence of 10.3% and a 12-month prevalence of 6.8%. CONCLUSIONS:
      Obsessions are common phenomena in the general population and are associated with
      decreased functioning in several areas of health and well-being. Furthermore,
      they occur frequently in the presence of various psychiatric disorders.
      Obsessions should be perceived, similar to delusions, as a distinct dimension
      across psychiatric disorders rather than a mere symptom of OCD.

PMID- 21898704
TI  - Effects of acute exercise on CO(2) -induced fear.
AB  - BACKGROUND: Acute exercise has shown to reduce the effects of experimental panic
      provocation in healthy volunteers and in patients with panic disorder. Recent
      evidence suggests that when larger amounts of CO(2) are inhaled, a large
      proportion of healthy subjects can also develop an affective response consistent
      with definitions of a panic attack. Our aim was to test whether exercise can show
      antipanic effects in healthy subjects when exposed to higher concentrations of
      CO(2). METHODS: Thirty-one healthy subjects, on four separate occasions in a
      randomized Latin square design, performed either moderate/hard or very-light
      exercise immediately followed by either a single or a double 35% CO(2)/65% O(2)
      inhalation. RESULTS: Compared to very-light exercise, when subjects performed
      moderate/hard exercise they reported a reduction in panic symptoms on the Panic
      Symptom List and the Visual Analogue Scale of Fear but no difference on the
      Visual Analogue Scale of Discomfort after a double CO(2) inhalation. After a
      single CO(2) inhalation, reductions were only seen on the Panic Symptom List.
      CONCLUSIONS: After intense exercise, subjects had less panic symptoms when
      exposed 35% CO(2), particularly after a double inhalation.

PMID- 21898705
TI  - Combined cognitive bias modification treatment for social anxiety disorder: a
      pilot trial.
AB  - BACKGROUND: Cognitive Bias Modification (CBM) is a promising treatment for Social
      Anxiety Disorder (SAD). However, previous randomized trials have not
      systematically examined the combination of CBM for attention (CBM-A) and
      interpretation (CBM-I) or the credibility and acceptability of these protocols.
      METHODS: We conducted a randomized, double-blind placebo-controlled trial (N =
      32) to examine the efficacy of a CBM treatment called Attention and
      Interpretation Modification (AIM) for SAD. AIM comprised eight, twice weekly
      computer sessions with no therapist contact. During AIM, participants (1)
      completed a dot probe task in which probes always followed neutral faces when
      paired with a disgust face, thereby directing attention away from threat and (2)
      completed a word-sentence association task in which they received positive
      feedback for making benign interpretations of word-sentence pairs and negative
      feedback for making negative interpretations. We also assessed participants'
      perceived credibility of and satisfaction with AIM. RESULTS: Participants
      receiving AIM reported significantly reduced self-reported (Liebowitz Social
      Anxiety Scale) symptoms of social anxiety relative to the placebo. These gains
      were also evident on a behavioral measure (performance on an impromptu speech).
      AIM met our benchmarks for credibility and acceptability in this community
      sample, although credibility ratings were modest. Participants reported that CBM
      I was more helpful than CBM-A. CONCLUSIONS: A combined CBM treatment produced
      medium-to-large effects on social anxiety. Participants rated AIM as moderately
      credibly and acceptable. Should these findings be replicated in larger samples,
      AIM has the potential to be a widely accessible and efficacious treatment for
      SAD.

PMID- 21898706
TI  - Proinflammatory and "resiliency" proteins in the CSF of patients with major
      depression.
AB  - BACKGROUND: A number of studies have shown that elevated levels of inflammatory
      cytokines may promote depression and suicidal ideation and that neuroprotective
      peptides may decrease the response to stress and depression. In this study,
      cerebrospinal fluid (CSF) levels of three inflammatory cytokines (IL-1, IL-6, and
      tumor necrosis factor alpha (TNFalpha)) and two putative "resiliency"
      neuropeptides (brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY))
      were compared between patients with depression and healthy controls. METHODS:
      Eighteen patients with major depression and 25 healthy controls underwent a
      lumbar puncture; CSF samples were withdrawn and assayed for IL-1, IL-6, TNFalpha,
      BDNF, and NPY levels. Patients with depression were then entered into an 8-week
      treatment protocol and had repeated lumbar puncture procedures post-treatment.
      RESULTS: Contrary to prediction, we found that at baseline depressed patients had
      higher CSF NPY concentration compared to the normal comparison group. Within the
      depressed patients, we found several statistically significant correlations
      between elevated CSF cytokine levels and clinical severity. CONCLUSION: Despite
      the small sample size, given the challenges in obtaining CSF from patients with
      depression these data are of interest in confirming some aspects of the
      inflammatory hypothesis of depression.

PMID- 21898707
TI  - Tools for translational neuroscience: PTSD is associated with heightened fear
      responses using acoustic startle but not skin conductance measures.
AB  - BACKGROUND: Posttraumatic stress disorder (PTSD) patients show heightened fear
      responses to trauma reminders and an inability to inhibit fear in the presence of
      safety reminders. Brain imaging studies suggest that this is in part due to
      amygdala over-reactivity as well as deficient top-down cortical inhibition of the
      amygdala. Consistent with these findings, previous studies, using fear
      potentiated startle (FPS), have shown exaggerated startle and deficits in fear
      inhibition in PTSD participants. However, many PTSD studies using the skin
      conductance response (SCR) report no group differences in fear acquisition.
      METHOD: The study included 41 participants with PTSD and 70 without PTSD. The
      fear conditioning session included a reinforced conditioned stimulus (CS+, danger
      cue) paired with an aversive airblast, and a nonreinforced conditioned stimulus
      (CS-, safety cue). Acoustic startle responses and SCR were acquired during the
      presentation of each CS. RESULTS: The results showed that fear conditioned
      responses were captured in both the FPS and SCR measures. Furthermore, PTSD
      participants had higher FPS to the danger cue and safety cue compared to trauma
      controls. However, SCR did not differ between groups. Finally, we found that FPS
      to the danger cue predicted re-experiencing symptoms, whereas FPS to the safety
      cue predicted hyper-arousal symptoms. However, SCR did not contribute to PTSD
      symptom variance. CONCLUSIONS: Replicating earlier studies, we showed increased
      FPS in PTSD participants. However, although SCR was a good measure of
      differential conditioning, it did not differentiate between PTSD groups. These
      data suggest that FPS may be a useful tool for translational research.

PMID- 21898708
TI  - Sooner or later: age at onset of generalized anxiety disorder in older adults.
AB  - BACKGROUND: Generalized anxiety disorder (GAD) is a common disorder in older
      adults, with widespread and long-lasting consequences. In this study, we assessed
      the characteristics associated with lifetime GAD in community-dwelling adults
      according to their age at onset of the disorder. METHODS: Study sample was
      extracted from the 2007 National Survey of Mental Health and Well Being, a
      nationally representative cross-sectional survey that interviewed 8,841
      Australians aged between 16 and 85 years using the Composite International
      Diagnostic Interview. Of the 3,178 participants aged 55-85 years, there were 227
      (M = 63.7 years; 65% female) with a lifetime diagnosis of GAD who were the focus
      of our analyses. RESULTS: Age at onset was defined as early (<26 years) or late
      (>= 26 years), based on the median age at onset for the entire sample. The
      weighted prevalence estimates for 12-month and lifetime GAD were 2.8% (95% CI:
      2.0, 3.7) and 7.0% (95% CI: 5.7, 8.3), respectively, with less than one-tenth of
      the participants being diagnosed after the age of 60 years. Having the first GAD
      episode earlier in life was significantly associated with physical abuse during
      childhood (OR = 0.34, 95% CI: 0.16, 0.75), lifetime diagnosis of dysthymia (OR =
      0.34, 95% CI: 0.18, 0.67), and number of GAD episodes (OR = 0.29, 95% CI: 0.14,
      0.58), after adjusting for current age and 12-month GAD. CONCLUSION: In older
      adults, an earlier age at onset of GAD was associated with childhood physical
      abuse and worse clinical outcomes, thus appearing to be a marker for increased
      vulnerability to GAD.

PMID- 21898710
TI  - Treatment-resistant depression in adolescents: review and updates on clinical
      management.
AB  - Treatment-resistant depression (TRD) in adolescents is prevalent and impairing.
      We here review the definition, prevalence, clinical significance, risk factors,
      and management of TRD in adolescents. Risk factors associated with TRD include
      characteristics of depression (severity, level of hopelessness, and suicidal
      ideation), psychiatric and medical comorbidities, environmental factors (family
      conflict, maternal depression, and history of abuse), and pharmacokinetics and
      other biomarkers. Management options include review of the adequacy of the
      initial treatment, re-assessment for the above-noted factors that might
      predispose to treatment resistance, switching antidepressants, and augmentation
      with medication or psychotherapy. Other modalities, such as electroconvulsive
      therapy, vagal nerve stimulation, and repetitive transcranial magnetic
      stimulation, are also reviewed.

PMID- 21898709
TI  - Newborn neurobehavioral patterns are differentially related to prenatal maternal
      major depressive disorder and serotonin reuptake inhibitor treatment.
AB  - BACKGROUND: Prenatal serotonin reuptake inhibitor (SRI) exposure has been related
      to adverse newborn neurobehavioral outcomes; however, these effects have not been
      compared to those that may arise from prenatal exposure to maternal major
      depressive disorder (MDD) without SRI treatment. This study examined potential
      effects of MDD with and without SRI treatment on newborn neurobehavior. METHODS:
      This was a prospective, naturalistic study. Women were seen at an outpatient
      research center twice during pregnancy (26-28 and 36-38 weeks gestational age
      (GA)). Psychiatric diagnoses were assessed using the Structured Clinical
      Interview for the DSM-IV; medication use was measured with the Timeline Follow
      Back instrument. Three groups were established based upon MDD diagnosis and SRI
      use: Control (N = 56), MDD (N = 20), or MDD + SRI (N = 36). Infants were assessed
      on a single occasion within 3 weeks of birth with the NICU Network
      Neurobehavioral Assessment Scale. Generalized Linear Modeling was used to examine
      neurobehavioral outcomes by exposure group and infant age at assessment. RESULTS:
      Full-term infants exposed to MDD + SRIs had a lower GA than CON or MDD-exposed
      infants and, controlling for GA, had lower quality of movement and more central
      nervous system stress signs. In contrast, MDD-exposed infants had the highest
      quality of movement scores while having lower attention scores than CON and MDD +
      SRI-exposed infants. CONCLUSION: MDD + SRI-exposed infants seem to have a
      different neurobehavioral profile than MDD-exposed infants in the first 3 weeks
      after delivery; both groups may have different neurobehavioral profiles with
      increasing age from birth.

PMID- 21898712
TI  - Auditory novelty processing is enhanced in obsessive-compulsive disorder.
AB  - BACKGROUND: Cognitive models propose that anxiety disorders are associated with
      an attentional bias toward potentially threatening stimuli. In this study, it was
      analyzed whether patients with obsessive-compulsive disorder (OCD) show enhanced
      responses of their event-related brain potentials to novel stimuli, either in a
      context of potential threat or in a neutral context. METHODS: In this study, 20
      OCD patients and 20 matched healthy control subjects performed a visual
      recognition task during which irrelevant repeated standard sounds and unitary
      novel sounds were interspersed. RESULTS: As expected, OCD patients showed an
      increase in the novelty-P3 amplitude elicited by unitary novel sounds. However,
      no effect of emotional context conditions was observed. CONCLUSION: It is
      suggested that the novelty P3 amplitude increase in OCD patients represents a
      physiological indicator of an enhanced cortical orienting response implicating
      stronger involuntary shifts of attention. This characteristic is driven by
      novelty per se and not moderated by potential threat of upcoming events.

PMID- 21898711
TI  - Improving the antidepressant efficacy of transcranial magnetic stimulation:
      maximizing the number of stimulations and treatment location in treatment
      resistant depression.
AB  - OBJECTIVE: To assess the efficacy of increasing the number of fast left
      repetitive transcranial magnetic stimulations (rTMS) (10 Hz @ 120% of motor
      threshold (MT) over the left dorsolateral prefrontal cortex (DLPFC)) needed to
      achieve remission in treatment-resistant depression (TRD). And, to determine if
      patients who do not remit to fast left will remit using slow right rTMS (1 Hz @
      120% MT over the right DLPFC). METHOD: Patients were part of a multicenter sham
      controlled trial investigating the efficacy of fast left rTMS. Patients who
      failed to meet minimal response criteria in the sham-controlled study could
      enroll in this open fast left rTMS study for an additional 3-6 weeks. Patients
      who failed to remit to fast left could switch to slow right rTMS for up to 4
      additional weeks. The final outcome measure was remission, defined as a HAM-D
      score of <3 or 2 consecutive HAM-D scores less than 10. RESULTS: Forty-three of
      141 (30.5%) patients who enrolled in the open phase study eventually met criteria
      for remission. Patients who remitted during fast left treatment received a mean
      of 26 active treatments (90,000 pulses). Twenty-six percent of patients who
      failed fast left remitted during slow right treatment. CONCLUSION: The total
      number of rTMS stimulations needed to achieve remission in TRD may be higher than
      is used in most studies. TRD patients who do not respond to fast left rTMS may
      remit to slow right rTMS or additional rTMS stimulations.

PMID- 21898713
TI  - Coping flexibility and complicated grief: a comparison of American and Chinese
      samples.
AB  - BACKGROUND: The ability to process a death and the ability to remain optimistic
      and look beyond the loss are both thought to be effective means of coping with
      loss and other aversive events. Recently, these seemingly contrary dimensions
      have been integrated into the idea of coping flexibility. METHODS: In this study,
      we assessed the ability of married and bereaved individuals in the United States
      and Hong Kong to use both coping approaches as operationalized by the trauma
      focused and forward-focused coping scales of a previously validated
      questionnaire. We also calculated a single flexibility score. RESULTS: Bereaved
      participants reported greater trauma-focused coping ability than did married
      participants. However, bereaved participants meeting criteria for complicated
      grief (CG) reported less forward-focused coping than both asymptomatic bereaved
      and married participants. The CG group also showed less overall coping
      flexibility than the asymptomatic bereaved and married groups. Country was not a
      factor. CONCLUSION: Findings suggest that deficits in coping flexibility are
      indicative of pathology in bereaved individuals, and that this relationship
      extends across cultures. Limitations of the study and directions for future
      research are discussed.

PMID- 21898714
TI  - Depression treatment and maternal functioning.
AB  - BACKGROUND: In women with major depressive disorder (MDD), maternal role
      functioning is negatively impacted but has been shown to improve with treatment;
      however, most investigations have not included a control group or studied women
      longitudinally. We hypothesized that women with MDD who responded to serotonin
      selective reuptake inhibitors (SSRIs) would have overall functioning and maternal
      role functioning scores similar to that of the control group and superior to
      women with MDD (either untreated or nonresponsive to SSRIs). METHODS: This
      prospective, longitudinal observational study (n = 215) included postpartum
      assessments at 2 1/2 weeks, 3 months, 6 months, and 12 months. Postpartum women
      were categorized into four mutually exclusive exposure groups by depression and
      medication status: (1) Control group (no SSRI, no MDD; (2) Responder (SSRI, no
      MDD); (3) Untreated (MDD, no SSRI); and (4) Nonresponder (Both MDD and SSRI).
      Outcome variables include a measure of overall functioning (Global Assessment
      Scale, GAS) and three measures of maternal role functioning (Maternal Self
      Efficacy, ICS; Gratification in Maternal Role, GRAT; and overall maternal role
      functioning, IFSAC). RESULTS: The study hypothesis was supported. Responders had
      scores related to overall functioning and maternal role functioning that were
      similar to the control group and superior to nonresponders and untreated women
      with MDD, as measured by the GAS and the GRAT. CONCLUSION: Postpartum depression
      treatment optimally targets both symptom improvement and maternal functional
      recovery. The GRAT is a simple, self-administered instrument that can be used
      with a depression measure to assess maternal role functioning.

PMID- 21898715
TI  - Incidence and predictors of relapse during continuation treatment of major
      depression with SSRI, interpersonal psychotherapy, or their combination.
AB  - BACKGROUND: Despite the availability of many effective treatments, patients with
      major depression remain at risk for relapse following remission of a depressive
      episode. The aims of this report are to estimate the relapse rates associated
      with the acute treatment strategies employed in this study and to investigate
      demographic and clinical predictors of relapse. METHODS: The study sample
      includes 225 patients who entered the 6-month continuation treatment phase after
      remitting from an acute depressive episode. Treatment during the acute phase was
      interpersonal psychotherapy, SSRI (escitalopram), or the combination of the two
      when monotherapy did not lead to response. Relapse was defined by a Hamilton
      Depression Rating Scale score >=15, confirmed by the diagnosis of major
      depression. The probability of relapsing was modeled using logistic regression.
      Three separate models were fit with subgroups of covariates. RESULTS: Of the 225
      patients, 29 (12.9%) relapsed and 28 (12.4%) discontinued the protocol
      prematurely. The proportion of patients who relapsed among the group requiring
      combination treatment to achieve remission was three times as high as among
      patients who had remitted with monotherapy. In the final logistic regression
      model, older age, higher baseline HDRS scores, last month (residual) depressive
      mood spectrum factor score, and requiring combination treatment to achieve
      remission were each associated with an increased likelihood of relapse.
      CONCLUSIONS: Our results suggest that greater initial depression severity,
      greater difficulty in stabilizing symptoms, and presence of residual mood
      spectrum symptoms once remission is achieved are predictive of relapse. Risk of
      relapse is more likely as age increases, partly because aging confers lower
      resilience.

PMID- 21898716
TI  - Cerebral responses to emotional expressions and the development of social anxiety
      disorder: a preliminary longitudinal study.
AB  - BACKGROUND: Cross-sectional studies report biased reactivity to facial
      expressions among shy children, anxious adolescents, and adults with social
      anxiety disorder (SAD). It remains unknown whether cerebral reactivity to facial
      expressions can predict longitudinally the development of SAD in adolescence and
      characterize the degree of social anxiety among the general population of
      adolescents. METHODS: In a longitudinal study of 21 general population volunteers
      characterized for behavioral and genetic variables, N400 event-related
      potentials, and 3-Tesla fMRI activations in response to happy/neutral/angry
      expressions were acquired at age 8-9 and 14-15, respectively. RESULTS: By
      stepwise regression, N400 amplitudes acquired at age 8-9 predicted the number of
      DSM-IV SAD symptoms at age 14-15, with the sole, significant (P = .018)
      contribution of the "anger" condition. Factorial ANOVA revealed increased (Voxel
      Level P((FWE))  range: .02-.0001) bilateral fMRI activations of several brain
      areas, including the amygdala, in response to facial expressions compared to a
      fixation cross. The number of symptoms of DSM-IV SAD was positively correlated
      with left amygdala response to angry (P((FWE))  = .036) and neutral (P((FWE))  =
      .025) facial expressions. Factorial ANOVA revealed that the 5-HTTLPR -S allele
      was associated with heightened left amygdala response to anger (P((FWE))  = .05).
      CONCLUSION: Cerebral reactivity to facial expressions, anger especially, measured
      at different developmental stages by different techniques is associated with
      adolescence SAD. The 5-HTTLPR genotype affects the neural processing of
      interpersonal affective stimuli during development.

PMID- 21898717
TI  - Does the presence of accompanying symptom clusters differentiate the comparative
      effectiveness of second-line medication strategies for treating depression?
AB  - BACKGROUND: We explored whether clinical outcomes differ by treatment strategy
      following initial antidepressant treatment failure among patients with and
      without clinically relevant symptom clusters. METHODS: The Sequenced Treatment
      Alternatives to Relieve Depression (STAR*D) trial was used to examine depression
      remission and response in patients with coexisting anxiety, atypical features,
      insomnia, and low energy. We applied propensity scoring to control for selection
      bias that precluded comparisons between augmentation and switch strategies in the
      original trial. Binomial regressions compared the likelihood of remission or
      response among patients with and without symptom clusters for switch versus
      augmentation strategies (n = 269 per arm); augmentation strategy type (n = 565);
      and switch strategy type (n = 727). RESULTS: We found no statistically
      significant difference in remission or response rates between augmentation or
      switch strategies. However, symptom clusters did distinguish among augmentation
      and switch strategies, respectively. For patients with low energy, augmentation
      with buspirone was less likely to produce remission than augmentation with
      bupropion (remission Risk Ratio (RR): 0.54, 95% CI: 0.35-0.85, response RR: 0.67,
      95% CI: 0.43, 1.03). Also, for patients with low energy, switching to venlafaxine
      or bupropion was less likely to produce remission than switching to sertraline
      (RR: 0.59, 95% CI: 0.36-0.97; RR: 0.63, 95% CI: 0.38-1.06, respectively).
      CONCLUSIONS: Remission and response rates following initial antidepressant
      treatment failure did not differ by treatment strategy for patients with
      coexisting atypical symptoms or insomnia. However, some second-step treatments
      for depression may be more effective than others in the presence of coexisting
      low energy. Subsequent prospective testing is necessary to confirm these initial
      findings.

PMID- 21898718
TI  - Buffalo (Bubalus bubalis) epiphyseal proteins give protection from arsenic and
      fluoride-induced adverse changes in acetylcholinesterase activity in rats.
AB  - The objective of this study was to determine the effect of fluoride (F) and
      arsenic (As) on the activity of acetylcholinesterase (AChE), a critically
      important nervous system enzyme, and to test the protective role of buffalo
      epiphyseal (pineal) proteins (BEP) in rats. Arsenic (20 mg/kg BW,
      intraperitoneally) and F (150 ppm, perorally) were exposed, and BEP was
      administered intraperitoneally (100 MU g/kg BW) along with F and As to rats for 7
      days. As and F exposure significantly (p < 0.05) increased their levels in plasma
      and decreased the activity of AChE in plasma, RBCs, heart, and brain of rats.
      Interestingly, As- and F-induced inhibition of AChE activities increased As and F
      levels in plasma, and organs were significantly (p < 0.05) counteracted by BEP
      administration. These findings indicate the protective role of buffalo (Bubalus
      bubalis) epiphyseal proteins on F- and As-induced adverse changes in AChE
      activity as a candidate biomarker for neurotoxicity in female rats.

PMID- 21898719
TI  - Induction of neuronal damage in guinea pig brain by intratracheal infusion of 2
      chloroethyl ethyl sulfide, a mustard gas analog.
AB  - Intratracheal infusion of 2-chloroethyl ethyl sulfide (CEES), a mustard gas
      analog and a chemical warfare agent is known to cause massive damage to lung. The
      purpose of this study was to determine whether intratracheal CEES infusion causes
      neuronal damage. Histological, immunohistochemical, and Western blot studies
      indicated that CEES treatment caused dose-dependent increases in blood cell
      aggregation, microglial cell number, microglial activation, and brain
      inflammation. In addition, an increased expression of alpha-synuclein and a
      decreased expression of the dopamine transporter were observed. The results
      indicate that intratracheal CEES infusion is associated with changes in brain
      morphology mediated by an increase in alpha-synuclein expression, leading to
      neurotoxicity in a guinea pig model. These changes may be mediated by oxidative
      stress. Furthermore, the present study indicates for the first time that
      intratracheal infusion of a single dose of CEES can cause neuroinflammation,
      which may lead to neurological disorders in later part of life.

PMID- 21898720
TI  - Enhanced cardioprotective effects by coexpression of two isoforms of hepatocyte
      growth factor from naked plasmid DNA in a rat ischemic heart disease model.
AB  - BACKGROUND: The therapeutic potential of pCK-HGF-X7, a naked DNA designed to
      express two isoforms of hepatocyte growth factor (HGF(723) and HGF(728) ), was
      studied in the rat ischemic heart disease model. METHODS: First, the kinetics of
      gene expression was examined by injecting pCK-HGF-X7 DNA into the rat heart.
      Second, the cardioprotective effects were compared between the two naked DNA
      constructs, expressing a single (HGF(728) ) or both isoforms (HGF(728) and
      HGF(723) ) of HGF, in the rat ischemic heart disease model. The ischemic injury
      to the rat heart was created by ischemia-reperfusion in the anterior descending
      artery. The respective naked DNA constructs were injected into the anterior wall
      of the rat heart with the ischemia-reperfusion injury. Cardiac function,
      capillary density and anti-fibrotic activity were compared between the two naked
      DNA constructs. RESULTS: The intramyocardial administration of pCK-HGF-X7
      resulted in transient and localized HGF expression for 3 weeks. At its peak,
      approximately 678 pg (per mg of tissue protein) of HGF was produced in the
      injected heart without an increase of HGF protein level in other tissues, and
      serum. pCK-HGF-X7 more efficiently improved the left ventricular ejection
      fraction and the systolic anterior wall thickness, increased the capillary
      density, and inhibited myocardial fibrosis, in a statistically significant
      manner, compared to the identical vector encoding HGF(728) only. CONCLUSIONS:
      These results demonstrate that transfer of the genomic-cDNA hybrid expressing
      both isoforms of the HGF gene might provide higher therapeutic effects than the
      cDNA sequence producing HGF(728) alone in the treatment of ischemic heart
      disease.

PMID- 21898721
TI  - Lentiviral-based BMP4 in vivo gene transfer strategy increases pull-out tensile
      strength without an improvement in the osteointegration of the tendon graft in a
      rat model of biceps tenodesis.
AB  - BACKGROUND: The present study aimed to develop a rat model of biceps tenodesis
      and to assess the feasibility of a lentiviral (LV)-based bone morphogenetic
      protein (BMP) 4 in vivo gene transfer strategy for healing of biceps tenodesis.
      METHODS: A rat model of biceps tenodesis was developed with an interference-fit
      open surgical technique. A LV vector expressing a BMP4 gene or beta-galactosidase
      (beta-gal) control gene was applied to the bone tunnel and the tendon graft
      before its insertion into the bone tunnel. Osteointegration was assessed by
      histology and pull-out tensile strength was measured by a biomechanical test
      suitable for small rat biceps tendon grafts. RESULTS: Neo-chondrogenesis was seen
      at the tendon-bone interface of LV-BMP4-treated but not control rats. The LV-BMP4
      treated rats showed 32% (p < 0.05) more newly-formed trabecular bone at the
      tendon-bone junction than the LV-beta-gal-treated controls after 3 weeks.
      However, the sites of neo-chondrogenesis and new bone formation in the LV-BMP4
      treated tenodesis were highly spotty. Although the LV-BMP4 strategy did not
      promote bony integration of the tendon graft, it yielded a 29.5 +/- 11.8% (p =
      0.066) increase in improvement the pull-out strength of rat biceps tendons
      compared to the LV-beta-gal treatment after 5 weeks. CONCLUSIONS: Although the LV
      BMP4 in vivo gene transfer strategy did not enhance osteointegration of the
      tendon graft, it yielded a marked improvement in the return of the pull-out
      strength of the tendon graft. This presumably was largely a result of the bone
      formation effect of BMP4 that traps or anchors the tendon graft onto the bony
      tunnel.

PMID- 21898722
TI  - Modular design in natural and biomimetic soft materials.
AB  - Under eons of evolutionary and environmental pressure, biological systems have
      developed strong and lightweight peptide-based polymeric materials by using the
      20 naturally occurring amino acids as principal monomeric units. These materials
      outperform their man-made counterparts in the following ways: 1)
      multifunctionality/tunability, 2) adaptability/stimuli-responsiveness, 3)
      synthesis and processing under ambient and aqueous conditions, and 4)
      recyclability and biodegradability. The universal design strategy that affords
      these advanced properties involves "bottom-up" synthesis and modular,
      hierarchical organization both within and across multiple length-scales. The
      field of "biomimicry"-elucidating and co-opting nature's basic material design
      principles and molecular building blocks-is rapidly evolving. This Review
      describes what has been discovered about the structure and molecular mechanisms
      of natural polymeric materials, as well as the progress towards synthetic
      "mimics" of these remarkable systems.

PMID- 21898724
TI  - Synthesis and reactions of N-heterocyclic carbene boranes.
AB  - Boranes are widely used Lewis acids and N-heterocyclic carbenes (NHCs) are
      popular Lewis bases, so it is remarkable how little was known about their derived
      complexes until recently. NHC-boranes are typically readily accessible and many
      are so stable that they can be treated like organic compounds rather than
      complexes. They do not exhibit "borane chemistry", but instead are proving to
      have a rich chemistry of their own as reactants, as reagents, as initiators, and
      as catalysts. They have significant potential for use in organic synthesis and in
      polymer chemistry. They can be used to easily make unusual complexes with a broad
      spectrum of functional groups not usually seen in organoboron chemistry. Many of
      their reactions occur through new classes of reactive intermediates including
      borenium cations, boryl radicals, and even boryl anions. This Review provides
      comprehensive coverage of the synthesis, characterization, and reactions of NHC
      boranes.

PMID- 21898723
TI  - Expanded click conjugation of recombinant proteins with ubiquitin-like modifiers
      reveals altered substrate preference of SUMO2-modified Ubc9.
AB  - Wrestling with SUMO: the chemical conjugation of proteins with small ubiquitin
      like modifiers (SUMO) can be achieved by a copper(I)-catalyzed cycloaddition and
      unnatural amino acid mutagenesis. This approach overcomes previous restrictions
      related to the primary sequence of proteins and coupling conditions. Moreover,
      biochemical data suggests that this triazole linkage presents the modifier in a
      proper distance and orientation relative to the target protein.

PMID- 21898725
TI  - Triple-layer (au@perylene)@polyaniline nanocomposite: unconventional growth of
      faceted organic nanocrystals on polycrystalline Au.
AB  - Unconventional crystal growth: core/shell nanocrystals were obtained by growth of
      a dominant single-crystalline phase of perylene over polycrystalline Au
      nanoparticle seeds and isolated by coating with polyaniline (PANI) shells.
      Perylene is released in the presence of sodium dodecyl sulfate (SDS) micelles.
      The TEM images show (Au@perylene)@PANI nanocomposites before and after complete
      release of perylene leaving Au@PANI (inset).

PMID- 21898726
TI  - TOPP: a novel nitroxide-labeled amino acid for EPR distance measurements.

PMID- 21898727
TI  - A general method for synthesis of GPI anchors illustrated by the total synthesis
      of the low-molecular-weight antigen from Toxoplasma gondii.
AB  - Building blocks: a new, general synthetic strategy, which allows the construction
      of branched glycosylphosphatidylinositols (GPIs), enables the synthesis of
      parasitic glycolipid 1 from Toxoplasma gondii. In addition, the structure is
      further confirmed by recognition of monoclonal antibodies.

PMID- 21898728
TI  - Generation of alpha,beta-unsaturated iminium ions by laser flash photolysis.
AB  - Two at a time: alpha,beta-Unsaturated iminium ions can be generated by laser
      flash photolysis of enaminophosphonium ions. The rate constants of their
      reactions with nucleophiles provide the first direct comparison of the
      electrophilicities of iminium ions derived from MacMillan's first- and second
      generation catalysts.

PMID- 21898729
TI  - Induced nanoelectrospray ionization for matrix-tolerant and high-throughput mass
      spectrometry.
AB  - No-contact rule: the title method is ultra-sensitive, high-throughput (4 samples
      per second), easily multiplexed, and is compatible with serum, urine, and
      concentrated salt solutions. Other features of this method, which avoids physical
      contact between the electrode and the solvent, include sample economy and the
      ability to produce both positive and negative-ion spectra in one cycle.

PMID- 21898730
TI  - Light-responsive capture and release of DNA in a ternary supramolecular complex.

PMID- 21898731
TI  - Interlayer-crosslinked micelle with partially hydrated core showing reduction and
      pH dual sensitivity for pinpointed intracellular drug release.

PMID- 21898733
TI  - Carbon dioxide in ionic liquid microemulsions.
AB  - Tailor-made emulsion: a CO(2) -in-ionic-liquid microemulsion was produced for the
      first time. The CO(2)-swollen micelles are "tunable" because the micellar size
      can be easily adjusted by changing the pressure of CO(2). The microemulsion has
      potential applications in materials synthesis, chemical reactions, and
      extraction.

PMID- 21898734
TI  - Domino reactions consisting of heterocyclization and 1,2-migration-redox-neutral
      and oxidative transition-metal catalysis.
AB  - Two cats, two paths: two novel domino reactions starting from 6-hydroxy-2-alkyl-2
      alkynylcyclohexanones have been discovered. While redox-neutral platinum
      catalysis gives rise to furans through a sequence of cyclization, 1,2-shift, and
      Grob fragmentation, oxidative copper catalysis provides an entry to bicyclic 2,3
      dihydrofurans. Upon cyclization and oxidation, an unusual benzilic acid
      rearrangement can take place in this case.

PMID- 21898735
TI  - Methyltransferase activity of an iridium center with methylpyridinium as
      methylene source.
AB  - Hop on, hop off: an iridium center transfers a methyl group from pyridinium to an
      aryl unit, using exclusively the pyridine-bound methyl group as a mild methylene
      source. The reaction also involves cleavage of an unactivated C(aryl)-H bond and
      nitrile solvent activation. The process is reminiscent of DNA methylation and
      entails the formation of two new C(sp(2))-C(sp(3)) bonds within the metal
      coordination sphere.

PMID- 21898736
TI  - Regio- and enantioselective hydroamination of dienes by gold(I)/menthol
      cooperative catalysis.
AB  - Alcohol is key: regio- and enantioselective hydroamination of 1,3-dienes has been
      achieved with the dinuclear catalyst (R)-DTBM-SEGPHOS. The rate and selectivity
      of the reaction are enhanced by alcohol additives like menthol, which coordinates
      the cationic gold(I) to generate a Bronsted acid that can participate in
      catalysis. Mbs=p-methoxybenzenesulfonyl.

PMID- 21898737
TI  - Capture and visualization of hydrogen sulfide by a fluorescent probe.

PMID- 21898738
TI  - Synthesis of a bicyclobutane fatty acid identified from the cyanobacterium
      Anabaena PCC 7120.
AB  - By design: a carbanion-mediated cyclization reaction cascade serves as the key
      final step in the total synthesis of a novel oxylipin, which features a strained
      bicyclo[1.1.0]butane conjugated to a labile vinyl epoxide.

PMID- 21898739
TI  - An organophilic pervaporation membrane derived from metal-organic framework
      nanoparticles for efficient recovery of bio-alcohols.

PMID- 21898740
TI  - Enantioselective total synthesis and studies into the configurational stability
      of bismurrayaquinone A.
AB  - Lost in rotation: the concise strategy of the first enantioselective total
      synthesis of bismurrayaquinone A utilized traceless stereochemical exchange to
      form an enantioenriched biphenyl core that was elaborated in a bidirectional
      manner to the natural product. Observed racemization on an unsuccessful initial
      route prompted studies into the configurational stability of bismurrayaquinone A
      and related biquinones.

PMID- 21898741
TI  - Low-cost copper zinc tin sulfide counter electrodes for high-efficiency dye
      sensitized solar cells.

PMID- 21898742
TI  - Purification and magnetic interrogation of hybrid Au-Fe3O4 and FePt-Fe3O4
      nanoparticles.
AB  - Purifying heterodimers: differential magnetic catch and release separation is
      used to purify two important hybrid nanocrystal systems, Au-Fe(3)O(4) and FePt
      Fe(3)O(4). The purified samples have substantially different magnetic properties
      compared to the as-synthesized materials: the magnetization values are more
      accurate and magnetic polydispersity is identified in morphologically similar
      hybrid nanoparticles.

PMID- 21898751
TI  - beta-Sheet-induced chirogenesis in polymerization of oligopeptides.
AB  - The origin of long homochiral biopolymers in living systems has recently been the
      focus of intense research. In one particular research line, scientists studied,
      experimentally and theoretically, chiral amplification obtained during peptide
      formation by polymerization of amino acid building blocks. It was suggested that
      processes leading to temporal or spatial separation, and thus, to the growth of
      homochiral polymers at the expense of their heterochiral counterparts, can
      explain the chirality observed in larger molecules. We introduce a simple model
      and stochastic simulation for the polymerization of amino acids and beta-sheet
      formation, showing the crucial effects of the beta sheets on the distributions of
      peptide lengths. When chiral affinities are included, racemic beta sheets of
      alternating homochiral strands lead to the formation of chiral peptides, the
      isotacticity of which increases with length, consistent with previous
      experimental results in aqueous solutions. The tendency to form isotactic
      peptides is shown for both initially racemic and initially nonracemic systems, as
      well as for closed and open systems. We suggest that these or similar mechanisms
      may explain the origin of chiroselectivity in prebiotic environments.

PMID- 21898752
TI  - Polydiacetylene vesicles containing alphaalpha-cyclodextrin and azobenzene as
      photocontrolled nanocarriers.

PMID- 21898753
TI  - Diabetes mellitus and risk of hepatocellular carcinoma: a systematic review and
      meta-analysis.
AB  - Studies of diabetes and hepatocellular carcinoma (HCC) yielded inconsistent
      findings. This meta-analysis was conducted to examine the association between
      diabetes and risk of HCC. Studies were identified by searching PUBMED and MEDLINE
      database up to February 2011. Pooled risk estimates were calculated using the
      random-effects model. Potential sources of heterogeneity were explored by
      subgroup analyses. A total of 17 case-control studies and 32 cohort studies were
      included in the meta-analysis. The combined risk estimate of all studies showed a
      statistically significant increased risk of HCC prevalence among diabetic
      individuals (RR = 2.31, 95% CI: 1.87-2.84). The pooled risk estimate of 17 case
      control studies (OR = 2.40, 95% CI: 1.85-3.11) was slightly higher than that from
      25 cohort studies (RR = 2.23, 95% CI: 1.68-2.96). Metformin treatment was
      potentially protective. On the contrary, long duration of diabetes and
      sulfonylureas or insulin treatment possibly increase HCC risk. Also meta-analysis
      of 7 cohort studies found a statistically significant increased risk of HCC
      mortality (RR = 2.43, 95% CI: 1.66-3.55) for individuals with (versus without)
      diabetes. This meta-analysis shows that diabetes is associated with moderately
      increased risk of HCC prevalence, as well as HCC mortality. Considering the
      rapidly increasing prevalence of diabetes mellitus, the study underlines the need
      for cancer prevention in diabetic individuals. Further investigation is needed to
      focus on the potential mechanism for the pathogenesis of HCC and the link between
      HCC and different types, severity, treatment and duration of diabetes.

PMID- 21898754
TI  - Effects of a combination of oral anti-diabetes drugs with basal insulin therapy
      on beta-cell function and glycaemic control in patients with newly diagnosed type
      2 diabetes.
AB  - BACKGROUND: Oral anti-diabetes drugs plus basal insulin (OAD + insulin) therapy
      in patients with newly diagnosed type 2 diabetes might improve beta-cell function
      and result in extended glycaemic remission. This randomised trial compared the
      effect on beta-cell function and diabetes remission rate between oral drug alone
      or with addition of basal insulin. METHODS: One hundred and twenty-nine patients,
      aged 35-50 years, were enrolled between June 2005 and June 2009. For initial
      correction of hyperglycaemia, patients with fasting plasma glucose >=9.0 mmol/L
      and HbA(1c) >= 9.0%, were randomly assigned to therapy with oral drugs + insulin
      or oral drugs alone. Treatment was stopped after normoglycaemia was maintained
      for 3 months. Patients were then followed-up with diet and physical exercise.
      Blood glucose, HbA(1c) and insulin were measured prior to treatment and at 1-year
      follow-up. RESULTS: More patients achieved target glycaemic control in the oral
      drugs + insulin group [98.3% (58 of 59)] in less time [(10.4 +/- 2.5) days] than
      those in the oral drug group [95.7% (67 of 70) and (12.4 +/- 3.4) days]. At 1
      year follow-up, more patients maintained target glycaemia without any drugs in
      the oral drug + insulin group than in the oral drug group [37.9% (22 of 58) vs
      20.9% (14 of 67)]. Both treatments improved homeostasis model assessment-beta
      (HOMA-beta) and homeostasis model assessment-insulin resistance (HOMA-IR)
      significantly. They had similar effects on insulin resistance [lg(HOMA-IR): (0.50
      +/- 0.09) vs (0.48 +/- 0.09), p = 0.23]. However, oral drugs + insulin could
      recover beta-cell function much more than OAD alone could [lg(HOMA-beta): (2.17
      +/- 0.14) vs (2.11 +/- 0.13), p = 0.03]. CONCLUSION: In newly diagnosed type 2
      diabetes, therapy with oral drugs + insulin has had favourable outcomes on
      recovery and maintenance of beta-cell function and protracted glycaemic remission
      compared with treatment with oral drugs alone.

PMID- 21898755
TI  - Discontinuation of statins among patients with type 2 diabetes.
AB  - BACKGROUND: Statins play an important role in the prevention of cardiovascular
      disease in type 2 diabetes. Several studies have reported low adherence with
      statins among patients with type 2 diabetes. Studies comparing discontinuation of
      statins compared with discontinuation of oral anti-diabetics within the same
      individuals before and after initiation of oral anti-diabetic drugs are not
      available. The aim of this study was to describe discontinuation among patients
      with type 2 diabetes prescribed statins prior to and after initiation of oral
      anti-diabetics and to compare statin discontinuation with discontinuation of oral
      anti-diabetics. METHODS: We report an observational cohort study among patients
      initiating treatment with statins prior to or after initiation of oral anti
      diabetics between 1999 and 2007. Patients were classified as starting statins
      prior to initiation (Prior users) or after initiation (After users) of anti
      diabetics. Discontinuation was defined as an interval of 180 days or more between
      the theoretical end date of a statin/anti-diabetic prescription and the
      dispensing date of the next statin/anti-diabetic prescription. RESULTS AND
      CONCLUSIONS: We included 3323 starters with oral anti-diabetic drugs in our
      study; 2072 patients initiated statins in the period of observation.
      Discontinuation rates for statins were higher compared with oral anti-diabetics
      (52.1 vs 15.0%). After users discontinued statin therapy more frequently compared
      to prior users (62.8 vs 48.2%). Discontinuation of statins is higher compared
      with anti-diabetic discontinuation. Patients starting statins after the
      initiation of oral anti-diabetic treatment are more likely to discontinue
      treatment than patients who initiate statins before the start of oral anti
      diabetics.

PMID- 21898756
TI  - Synthesis and properties of a new red luminescence europium complex containing a
      2-(benzimidazol-2-yl)-8-octyloxyquinoline as the second ligand.
AB  - A new Eu(III) complex, Eu(III)(DBM)(3) BIOQ, has been synthesized with
      dibenzoylmethane (DBM) as the first ligand and 2-(benzimidazol-2-yl)-8
      octyloxyquinoline (BIOQ) as the second ligand. The stability of the complex was
      analysed by DSC-TG. The results show that the Eu(III) complex has a relatively
      high thermal stability with a melting point of 235  degrees C and a decomposition
      temperature (onset) of 252  degrees C. The fluorescence properties of the
      compound were also investigated. The fluorescence results reveal that the as
      prepared complex shows the characteristic maximum emission spectra of Eu(III) at
      611 nm (lambda(ex) = 350 nm). In addition, the photoluminescence spectrum of the
      complex in the solid state exhibits a single and symmetrical emission band at 611
      nm, with a full width at half-maximum of 4.7 nm, showing high colour purity. This
      finding indicates the possibility for the development of brighter red luminescent
      materials.

PMID- 21898757
TI  - Distribution and frequency of VKORC1 sequence variants conferring resistance to
      anticoagulants in Mus musculus.
AB  - BACKGROUND: Emerging resistance to anticoagulant rodenticides may significantly
      impair house mouse (Mus musculus L.) control. As in humans and rats, sequence
      variants in the gene vitamin K epoxide reductase complex subunit 1 (VKORC1) of
      house mice are strongly implicated in the responses of mice to anticoagulants.
      This study gives a first overview of the distribution and frequency of such
      potentially resistance-conferring sequence variants in house mice, based on
      tissue samples from 30 populations in Germany, Switzerland and the Azores.
      RESULTS: Except for one population from south Germany, sequence variants were
      found in individuals from all locations sampled (29 out of 30 sites surveyed),
      with less than 10% of the individuals matching the wild-type genotype. The most
      frequent and widespread amino acid substitutions were Leu128Ser, Tyr139Cys and a
      group of linked sequence changes (Arg12Trp/Ala26Ser/Ala48Thr/Arg61Leu). Where
      these substitutions occurred as the sole variant, the proportion of homozygous
      individuals was 72-83%. CONCLUSIONS: An evaluation of published data revealed
      that the three most frequently found sequence variants are associated with a
      substantial loss of rodenticide efficacy of first-generation anticoagulants (e.g.
      warfarin, coumatetralyl), as well as the second-generation compound bromadiolone
      and most probably also difenacoum. Knowledge of the distribution and frequency of
      resistance-conferring sequence variants will stimulate their further functional
      characterisation and facilitate the choice of effective active substances for
      house mouse control.

PMID- 21898758
TI  - Current- and past-use pesticide prevalence in drainage ditches in the Lower
      Mississippi Alluvial Valley.
AB  - BACKGROUND: Pesticide application is common in agriculture and often results in
      applied pesticides entering adjacent aquatic systems. This study seasonally
      analyzed a suite of 17 current- and past-use pesticides in both drainage waters
      and sediments to evaluate the prevalence of pesticides in drainage ditches across
      the Lower Mississippi Alluvial Valley (LMAV). RESULTS: There were significantly
      higher concentrations (P<0.05) of current-use than past-use pesticides; however,
      there were consistently high numbers of detections of past-use pesticides in
      sediments. Sediment pesticide concentrations were an order of magnitude higher
      (150-1035 ug kg(-1)) than water samples (6-20.9 ug L(-1)). Overall, 87% of all
      samples analyzed for current- and past-use pesticides were non-detects. p,p'-DDT
      was detected in 47.5% of all drainage waters and sediments sampled. There were
      significant correlations (0.372>=r2<=0.935) between detected current-use water
      and sediment concentrations, but no significant correlations between past-use
      water and sediment concentrations. CONCLUSION: Overall, there was a high
      percentage (87%) of sediment and water samples that did not contain detectable
      concentrations above the lower limit of analytical detection for each respective
      pesticide. This lack of pesticide prevalence highlights the improved conditions
      in aquatic systems adjacent to agriculture and a potential decrease in toxicity
      associated with pesticides in agricultural landscapes in the LMAV.

PMID- 21898759
TI  - A historic account of the invasion of Drosophila suzukii (Matsumura) (Diptera:
      Drosophilidae) in the continental United States, with remarks on their
      identification.
AB  - BACKGROUND: Drosophila suzukii is an oriental species first reported outside Asia
      from Hawaii in 1980. The first confirmed records for the continental United
      States were made in 2008 in California. The identification of this pest is
      difficult because very few published resources exist. RESULTS: It has since been
      recorded in Oregon, Washington, British Columbia, Alberta, Manitoba, Ontario,
      Quebec, Utah, Michigan, Wisconsin, Louisiana, North Carolina, South Carolina and
      Florida. Males are relatively easy to identify by the black apical wing spots and
      the single row of combs on the first and second tarsal segment of the fore leg.
      The male genitalia are also very characteristic and will aid in identifying
      teneral specimens. Females can be identified by the large ovipositor, which is 6
      7 times as long as the diameter of the spermatheca. Immature stages can only be
      identified by molecular techniques. CONCLUSION: Although this species has been
      recorded from many US states and Canadian provinces, it has not been established
      in all of these places, and the main economic damage is restricted to the western
      part of North America. With the characters laid out in this paper, it should be
      possible to identify the pest with high certainty.

PMID- 21898760
TI  - IPM program development for an invasive pest: coordination, outreach and
      evaluation.
AB  - BACKGROUND: Spotted wing drosophila (SWD), Drosophila suzukii Matsumura, was
      found along the west coast of the United States, beginning in 2008 and 2009,
      infesting a wide variety of small and stone fruit crops. This pest is a serious
      economic threat, as noted in its native range (Asia), because it lays eggs within
      ripening fruit before harvest, leading to crop loss. The aim of this paper is to
      describe the process in order to create collaboration, communication routes and
      evaluation methods in response to a new invasive pest. RESULTS: Funding was
      secured and a program (SWD*IPM) was quickly developed to address social, economic
      and biological components. Communication routes were outlined, and a stakeholder
      advisory panel was established to guide program objectives. A central website was
      created to host up-to-date information. An online monitoring and mapping program
      for D. suzukii in Oregon fruit-growing regions illustrated the range,
      distribution and seasonal abundance of the pest. In addition, a program for
      backyard fruit growers was initiated to examine citizen scientists' roles in
      managing D. suzukii infestations in the urban setting. A monitoring kit,
      laminated educational cards, dry fly mounts and quick-time videos were some of
      the tools used to educate growers. First-year challenges for dealing with a new
      pest are discussed. CONCLUSION: The discovery and subsequent response to an
      exotic pest is information intensive and requires a well-planned, coordinated
      Extension and evaluation effort.

PMID- 21898761
TI  - DNApol-epsilon gene is indispensable for the survival and growth of Drosophila
      melanogaster.
AB  - Based on deletion and complementation mapping and DNA sequencing, a new recessive
      fully penetrant mutation (DNApol-epsilonpl10R), causing prolonged larval life and
      larval/early pupal lethality, is identified as the first mutant allele of the
      DNApol-epsilon (CG6768) gene of Drosophila melanogaster. A same-sense base pair
      substitution in exon 1 of the DNApol-epsilon gene is associated with retention of
      the first intron and significant reduction in DNApol-epsilon transcripts in
      DNApol-epsilonpl10R homozygotes. Homozygous mutant larvae show small imaginal
      discs with fewer cells and reduced polyteny in salivary glands, presumably
      because of the compromised DNA polymerase function following exhaustion of the
      maternal contribution. Extremely small and rare DNApol-epsilonpl10R homozygous
      somatic clones in DNApol-epsilonpl10R/+imaginal discs confirm their poor mitotic
      activity. The DNApol-epsilonpl10R homozygotes, like those expressing DNApol
      epsilon-RNAi transgene, show high sensitivity to DNA damaging agents. The first
      mutant allele of the DNApol-epsilon gene will facilitate functional
      characterization of this enzyme in the genetically tractable Drosophila model.

PMID- 21898762
TI  - X chromosome inactivation: a silence that needs to be broken.
AB  - Each mammalian female cell transcriptionally inactivates one X chromosome to
      balance X-linked gene dosage between males and females. This phenomenon, called X
      chromosome inactivation, is a perfect epigenetic event, in which two chromosomes
      with identical DNA sequences are solely distinguished by epigenetic
      modifications. In this case, epigenetic marks, such as histone modifications,
      histone variants, DNA methylation, and ncRNAs, are all enriched on one
      chromosome, the inactive X chromosome (Xi), to establish its chromosome-wide gene
      silencing. At face value, it seems that the gene silencing mechanism of Xi is
      well understood. However, the "silence" of Xi in somatic cells is so tightly
      maintained that it remains largely intact even after almost all known epigenetic
      modifications are artificially depleted. To understand how the gene silence of Xi
      is maintained in soma is a major challenge in current research. We summarize the
      current knowledge related with this issue and discuss future research directions.

PMID- 21898763
TI  - A novel TaulacZ allele reveals a requirement for Pitx2 in formation of the
      mammillothalamic tract.
AB  - The hypothalamic mammillary region is critical for spatial memory and vestibular
      processing. Pitx2 encodes a paired-like transcription factor that is highly
      expressed in the developing mammillary region and is required for subthalamic
      nucleus formation. Here we analyzed a loss of function Pitx2-TaulacZ knock-in
      allele to study the effects of Pitx2 deficiency on neuronal projections in the
      embryonic mammillary region. Pitx2-expressing neurons contribute axons to
      principal mammillary, mammillotegmental and mammillotectal tracts. Embryos with
      Pitx2 deficiency exhibit axonal fibers in the principal mammillary tract that are
      improperly bundled and disorganized, yet project caudally toward the tectum and
      tegmentum. Embryos with Nestin-Cre mediated conditional Pitx2 deficiency exhibit
      truncated mammillothalamic tracts (mtt) that fail to elongate, and reduced Pax6
      positive cells at the branching point of the principal mammillary and mtt. These
      data suggest that Pitx2 mediates cell-autonomous and nonautonomous guidance cues
      necessary for mammillary collaterals destined to project to the anterior
      thalamus.

PMID- 21898764
TI  - Mouse transgenic lines that selectively label Type I, Type IIA, and Types IIX+B
      skeletal muscle fibers.
AB  - Skeletal muscle fibers vary in contractile and metabolic properties. Four main
      fiber types are present in mammalian trunk and limb muscles; they are called I,
      IIA, IIX, and IIB, ranging from slowest- to fastest-contracting. Individual
      muscles contain stereotyped proportions of two or more fiber types. Fiber type is
      determined by a combination of nerve-dependent and -independent influences,
      leading to formation of "homogeneous motor units" in which all branches of a
      single motor neuron form synapses on fibers of a single type. Fiber type
      composition of muscles can be altered in adulthood by multiple factors including
      exercise, denervation, hormones, and aging. To facilitate analysis of muscle
      development, plasticity, and innervation, we generated transgenic mouse lines in
      which Type I, Type IIA, and Type IIX+B fibers can be selectively labeled with
      distinguishable fluorophores. We demonstrate their use for motor unit
      reconstruction and live imaging of nerve-dependent alterations in fiber type.

PMID- 21898765
TI  - Signaling and gene regulatory programs in plant vascular stem cells.
AB  - A key question about the development of multicellular organisms is how they
      precisely control the complex pattern formation during their growth. For plants
      to grow for many years, a tight balance between pluripotent dividing cells and
      cells undergoing differentiation should be maintained within stem cell
      populations. In this process, cell-cell communication plays a central role by
      creating positional information for proper cell type patterning. Cell-type
      specific gene regulatory networks govern differentiation of cells into particular
      cell types. In this review, we will provide a comprehensive overview of emerging
      key signaling and regulatory programs in the stem cell population that direct
      morphogenesis of plant vascular tissues.

PMID- 21898766
TI  - Characterization of transgenic mice expressing cancer-associated variants of
      human NOTCH1.
AB  - The Notch1 receptor plays a critical role in cell fate decisions during
      development. Activation of Notch signaling has been implicated in several types
      of cancer, particularly T-cell acute lymphoblastic leukemia (T-ALL).
      Consequently, several transgenic mouse strains have been made to study the role
      of Notch1 in T-ALL. However, the existing Notch1 transgenic lines mimic a
      translocation event found in only ~1% of T-ALL cases. Here we describe three
      novel NOTCH1 transgenic mouse strains that have Cre-inducible expression of the
      entire human NOTCH1 locus, each possessing a common mutation found in T-ALL.
      Unlike existing Notch1 transgenic strains, these NOTCH1 transgenic strains
      express full-length receptors from an endogenous human promoter that should be
      susceptible to a number of Notch antagonists that have recently been developed.
      These strains will allow researchers to modulate Notch signaling to study both
      normal development and cancer biology.

PMID- 21898767
TI  - Organ quality and quality of life after liver transplantation.
AB  - Not only is there a limited supply of organs for liver transplantation, but the
      quality of the available organs is not uniform. Risk factors such as donor age
      and cause of death are known to predict graft failure, but their impact on the
      recipient's quality of life (QOL) has not been reported. We sent a QOL survey to
      299 adults at our institution who had received a liver transplant 1 to 7 years
      before the study. For the 171 patients (57%) who completed the Medical Outcomes
      Study Short Form 36 (SF-36), the mean Physical Composite Score (PCS) and the mean
      Mental Composite Score (MCS) were 61 and 66, respectively; the highest scores
      were for the Social Functioning subscale, and the lowest scores were for the Role
      Functioning/Physical and Energy/Fatigue subscales. The mean donor risk index
      (DRI) of the organs that the subjects received was 1.4 (range = 0.8-2.4). There
      was no correlation between the SF-36 scores and the DRI [there were changes of 
      4.8 and -2.8 in the PCS and MCS per unit increase in the DRI (P = 0.4 and 0.6,
      respectively)], even though we controlled for potential confounders such as age,
      sex, hospitalization before transplantation, the Model for End-Stage Liver
      Disease score at transplantation, years since transplantation, previous
      transplantation, and the Charlson comorbidity index. In conclusion, we found no
      association between organ quality and QOL after liver transplantation. If this
      finding is confirmed in prospective, multicenter studies, it will be useful in
      counseling patients about the decision to accept or not accept high-risk organ
      offers.

PMID- 21898768
TI  - Submaximal cardiopulmonary exercise testing predicts 90-day survival after liver
      transplantation.
AB  - Liver transplantation has a significant early postoperative mortality rate. An
      accurate preoperative assessment is essential for minimizing mortality and
      optimizing limited donor organ resources. This study assessed the feasibility of
      preoperative submaximal cardiopulmonary exercise testing (CPET) for determining
      the cardiopulmonary reserve in patients being assessed for liver transplantation
      and its potential for predicting 90-day posttransplant survival. One hundred
      eighty-two patients underwent CPET as part of their preoperative assessment for
      elective liver transplantation. The 90-day mortality rate, critical care length
      of stay, and hospital length of stay were determined during the prospective
      posttransplant follow-up. One hundred sixty-five of the 182 patients (91%)
      successfully completed CPET; this was defined as the ability to determine a
      submaximal exercise parameter: the anaerobic threshold (AT). Sixty of the 182
      patients (33%) underwent liver transplantation, and the mortality rate was 10.0%
      (6/60). The mean AT value was significantly higher for survivors versus
      nonsurvivors (12.0 +/- 2.4 versus 8.4 +/- 1.3 mL/minute/kg, P < 0.001). Logistic
      regression revealed that AT, donor age, blood transfusions, and fresh frozen
      plasma transfusions were significant univariate predictors of outcomes. In a
      multivariate analysis, only AT was retained as a significant predictor of
      mortality. A receiver operating characteristic curve analysis demonstrated
      sensitivity and specificity of 90.7% and 83.3%, respectively, with good model
      accuracy (area under the receiver operating characteristic curve = 0.92, 95%
      confidence interval = 0.82-0.97, P = 0.001). The optimal AT level for survival
      was defined to be >9.0 mL/minute/kg. The predictive value was improved when the
      ideal weight was substituted for the actual body weight of a patient with
      refractory ascites, even after a correction for the donor's age. In conclusion,
      the preoperative cardiorespiratory reserve (as defined by CPET) is a sensitive
      and specific predictor of early survival after liver transplantation. The
      predictive value of CPET requires further evaluation.

PMID- 21898769
TI  - Factors associated with the postoperative status of donor patients for living
      donor liver transplantation.
AB  - Deceased donor liver transplantation has been an established surgical procedure
      since the 1960s. More recently, the technique of living donor liver
      transplantation (LDLT) was introduced, and it is being performed with increasing
      frequency. However, there is a paucity of information on the clinical outcomes of
      donor patients. In this study, which was conducted at a single university
      hospital, the relationship between potentially relevant factors (eg, patient
      characteristics, preoperative status, and operation characteristics) and
      postoperative developments in donor patients was examined. We used electronic
      critical pathways, which are charts of medical process that include favorable
      states (defined as outcomes) to be achieved during the hospital stay of a
      patient; predefined outcomes that are not achieved are recorded as variances.
      With the electronic critical pathway system, objective data about the conditions
      of patients and relevant clinical processes could be collected readily. Using
      data from the electronic critical pathways for LDLT donor patients and applying
      multiple logistic regression analysis, we examined factors that were related to
      the variance of each outcome measure for postoperative developments. Among the
      various donor characteristics, the duration of the operation was related to
      variance in 5 types of health outcomes, age and blood loss volume were related to
      variance in 2 types of health outcomes, and other characteristics (ie, sex, body
      surface area, operation urgency, and volume ratio of the remnant liver) were
      related to variance in 1 type of health outcome. In conclusion, the findings in
      this study may facilitate improvements in the postoperative status of LDLT donor
      patients. Further studies that incorporate analogous data from other medical
      facilities are necessary to verify these findings.

PMID- 21898770
TI  - Transjugular intrahepatic portosystemic shunts.

PMID- 21898771
TI  - Hot-topic debate on kidney function: renal-sparing approaches are ineffective.
AB  - KEY POINTS: 1. Both acute kidney injury and chronic renal disease are common in
      patients undergoing liver transplantation. The etiologies are mixed. 2. The
      incidence of chronic renal failure after liver transplantation is unacceptable,
      and it has a significant impact on long-term outcomes after liver
      transplantation. 3. The role of calcineurin inhibitors (CNIs) in the development
      of posttransplant chronic renal failure is likely overrated. 4. The use of CNIs
      in the early posttransplant period is currently essential. 5. Whether new agents
      will be able to provide effective immunosuppression as primary immunosuppressives
      remains to be proven.

PMID- 21898773
TI  - Predictors of the feasibility of primary endoscopic management of biliary
      strictures after adult living donor liver transplantation.
AB  - Biliary strictures are a major cause of morbidity and mortality for liver
      transplant recipients. The endoscopic management of biliary strictures is not
      well established after living donor liver transplantation (LDLT) in comparison
      with deceased donor liver transplantation. The aims of this study were to assess
      the initial success rate of primary endoscopic treatment of biliary strictures
      after LDLT and to identify predictors of the feasibility of endoscopic
      management. One hundred thirty-seven adult patients who underwent LDLT and were
      confirmed to have biliary strictures by endoscopic retrograde
      cholangiopancreatography (ERCP) were enrolled. The biliary strictures were
      primarily managed endoscopically with internal drainage or nasobiliary
      catheterization. The initial success rate for the primary endoscopic management
      of biliary strictures after LDLT was 46.7% (64 of 137 patients), and the
      feasibility of endoscopic management was associated with the stricture-to-ERCP
      interval (the interval between the development of the total bilirubin, aspartate
      aminotransferase, or alanine aminotransferase level to >2 times the upper limit
      of normal and the performance of ERCP) as well as cholangiographic findings (eg,
      the stricture morphology and the tip shape of the distal duct). In conclusion,
      when biliary strictures are noticed after LDLT, prompt endoscopic interventions
      may improve the initial success rate of primary endoscopic management. In
      addition, the feasibility of primary endoscopic management can be predicted by
      the cholangiographic findings, which may help with the choice of the therapeutic
      modality.

PMID- 21898774
TI  - Gold-gold junction electrodes:the disconnection method.
AB  - The formation of gold-gold junction electrodes for application in electroanalysis
      is described here based on electro-deposition from a non-cyanide gold plating
      bath. Converging growth of two hemispherical gold deposits on two adjacent
      platinum microelectrodes (both 100 um diameter in glass, ca. 45 um gap) followed
      by careful etching in aqueous chloride solution was employed. During growth both
      gold hemispheres "connect" and during etching "disconnection" is evident in a
      drop in current. Gold-gold junctions with sub-micron gaps are formed and applied
      for the electroanalytical detection of sub-micromolar concentrations of
      hydroquinone in 0.1 M phosphate buffer pH 7 (E(rev) = 0.04 V vs. SCE) and sub
      micromolar concentration of dopamine in 0.1 M phosphate buffer pH 7 (E(rev) =
      0.14 V vs. SCE). The potential future uses in analysis and limitations of gold
      gold junction electrodes are discussed.

PMID- 21898775
TI  - pi-Conjugated molecules covered by permethylated cyclodextrins.
AB  - Insulated pi-conjugated molecules, in which the pi-conjugated compounds are
      covered by a cyclic protective sheath, have attracted considerable attention
      because of their potential applicability in next-generation mono-molecular
      electronic devices. We have developed new methods of synthesizing insulated pi
      conjugated molecules involving the self-inclusion of rotaxane precursors linking
      pi-conjugated units as a guest and permethylated cyclodextrin (PMCD) as a
      macrocyclic host. The insulated pi-conjugated molecules thus formed are highly
      soluble in organic solvents and display photoluminescence efficiency. This paper
      also highlights a new method for synthesizing insulated molecular wire (IMW)
      through the polymerization of insulated pi-conjugated molecules as monomers. The
      IMWs thus formed have a high covering ratio, rigidity, and showed high charge
      mobility in the solid state; further, they are readily soluble in a variety of
      organic solvents. In this account, the synthetic methodologies and characteristic
      of insulated pi-conjugated molecules and IMWs are discussed.

PMID- 21898772
TI  - Epidemiology and outcome of infections in human immunodeficiency virus/hepatitis
      C virus-coinfected liver transplant recipients: a FIPSE/GESIDA prospective cohort
      study.
AB  - Information about infections unrelated to acquired immunodeficiency syndrome
      (AIDS) in human immunodeficiency virus (HIV)-infected liver recipients is scarce.
      The aims of this study were to describe the prevalence, clinical characteristics,
      time of onset, and outcomes of bacterial, viral, and fungal infections in
      HIV/hepatitis C virus (HCV)-coinfected orthotopic liver transplant recipients and
      to identify risk factors for developing severe infections. We studied 84
      consecutive HIV/HCV-coinfected patients who underwent liver transplantation at 17
      sites in Spain between 2002 and 2006 and were followed until December 2009. The
      median age was 42 years, and 76% were men. The median follow-up was 2.6 years
      (interquartile range = 1.25-3.53 years), and 54 recipients (64%) developed at
      least 1 infection. Thirty-eight (45%) patients had bacterial infections, 21 (25%)
      had cytomegalovirus (CMV) infections (2 had CMV disease), 13 (15%) had herpes
      simplex virus infections, and 16 (19%) had fungal infections (7 cases were
      invasive). Nine patients (11%) developed 10 opportunistic infections with a 44%
      mortality rate. Forty-three of 119 infectious episodes (36%) occurred in the
      first month after transplantation, and 53 (45%) occurred after the sixth month.
      Thirty-six patients (43%) had severe infections. Overall, 36 patients (43%) died,
      and the deaths were related to severe infections in 7 cases (19%). Severe
      infections increased the mortality rate almost 3-fold [hazard ratio (HR) = 2.9,
      95% confidence interval (CI) = 1.5-5.8]. Independent factors for severe
      infections included a pretransplant Model for End-Stage Liver Disease (MELD)
      score >15 (HR = 3.5, 95% CI = 1.70-7.1), a history of AIDS-defining events before
      transplantation (HR = 4.0, 95% CI = 1.9-8.6), and non-tacrolimus-based
      immunosuppression (HR = 2.5, 95% CI = 1.3-4.8). In conclusion, the rates of
      severe and opportunistic infections are high in HIV/HCV-coinfected liver
      recipients and especially in those with a history of AIDS, a high MELD score, or
      non-tacrolimus-based immunosuppression.

PMID- 21898776
TI  - The smallest man-made jet engine.
AB  - The design of catalytic engines powered by chemical fuels is an exciting and
      emerging field in multidisciplinary scientific communities. Recent progress in
      nanotechnology has enabled scientists to shrink the size of macroengines down to
      microscopic, but yet powerful, engines. Since a couple of years ago, we have
      reported our progress towards the control and application of catalytic
      microtubular engines powered by the breakdown of hydrogen peroxide fuel which
      produces a thrust of oxygen bubbles. Efforts were undertaken in our group to
      prove whether the fabrication of nanoscale jets is possible. Indeed, the smallest
      jet engine (600 nm in diameter and 1 picogram of weight) was synthesized based on
      heteroepitaxially grown layers. These nanojets are able to self-propel in
      hydrogen peroxide solutions and are promising for the realisation of multiple
      tasks.

PMID- 21898778
TI  - Molecular catalysis for fullerene functionalization.
AB  - This account highlights elements of our efforts to explore new functionalization
      chemistry of fullerenes using molecular catalysts since 2006. These endeavors
      have led to the development of new reactions such as (i) organoboron addition to
      fullerenes, (ii) C-H bond allylation and arylation of organo(hydro)fullerenes,
      (iii) C-H/C-C bond cleavage of alkynyl(hydro)fullerenes, (iv) regioselective
      tetraallylation of fullerenes, (v) double nucleophilic substitution of
      aziridinofullerene, and (vi) [2+2] cycloaddition of aziridinofullerene with
      alkynes. These works not only highlight the potential of molecular catalysis for
      fullerene functionalization, but also unlock opportunities for markedly different
      strategies in nanocarbon synthesis.

PMID- 21898777
TI  - Construction of contiguous tetrasubstituted chiral carbon stereocenters via
      direct catalytic asymmetric aldol and Mannich-type reactions.
AB  - Catalytic asymmetric synthesis of unnatural amino acids with vicinal
      tetrasubstituted chiral carbon stereocenters is described. In the first part,
      direct catalytic asymmetric aldol reaction of simple non-activated ketone
      electrophiles with alpha-substituted alpha-isothiocyanato ester donors was
      realized. A Mg/Schiff base catalyst promoted the aldol reaction, and alpha-amino
      beta-hydroxy esters were obtained in up to 98% ee and 98:2 d.r. In the second
      part, the Mg/Schiff base catalyst and a Sr/Schiff base catalyst were utilized for
      stereodivergent direct asymmetric Mannich-type reaction of ketimines. The
      Mg/Schiff base catalyst gave syn-alpha,beta-diamino esters, while the Sr/Schiff
      base catalyst produced anti-alpha,beta-diamino esters in good to high
      enantioselectivity, up to 97% ee.

PMID- 21898779
TI  - Hydroarylation of alkynes catalyzed by nickel.
AB  - Nickel catalysts derived from bis(1,5-cyclooctadiene)nickel [Ni(cod)(2)] and
      trialkylphosphines effect hydroarylation of alkynes through functionalization of
      C-H bonds of arenes including benzo-fused five-membered heteroarenes, pyridine-N
      oxides, pyridines, 2-pyridones, and perfluoroarenes. The reactions proceed with
      excellent stereo- and regioselectivity to give disubstituted arylethenes in good
      yields. Use of Lewis acid (LA) co-catalysts is crucial for success in reactions
      of imidazoles, pyridines, and 2-pyridones; it is possible that coordination of
      the LA to the nitrogen or oxygen functionalities of such substrates increases the
      reactivity of their C-H bonds towards nickel(0) species.

PMID- 21898780
TI  - Catalytic migratory oxidative coupling of nitrones through an outer-sphere C(sp3)
      H activation process.
AB  - Outer-sphere redox catalysis is key to efficient C-H activation, which has
      attracted increased interest in organic chemistry. In this account, we describe a
      Cu(I) -catalyzed oxidative coupling between nitrones and various ethers or amines
      as an example. Predictable site-selective C-C bond formation was achieved through
      activation of the C-H bonds in each coupling partner and the migration of a C-N
      double bond. Mechanistic studies strongly suggested that the reaction proceeded
      via an oxonium/iminium cation species as the key intermediate. The mechanistic
      information allows for future extension of outer-sphere redox catalysis.

PMID- 21898781
TI  - Synthetic challenge to ubiquitous natural products from plant origin: flavan
      derived polyphenols.
AB  - Flavan-derived polyphenols (catechin derivatives), widely destributed in the
      plant kingdom, have been given much considerable attention owing to their
      significant bioactivitites coupled with their extreme structural diversity.
      However, biochemical functions of this class of molecules are still not well
      understood because of the limited availavility of natural samples in sufficient
      quantity and quality. Here we report our synthetic challenges toward flavan
      derived polyphenols, based on the flavonoid-sugar analogy. The key for success
      was the C(4)-elaboration of the flavan skeleton, which posed an important
      relevance to their structure diversification both in terms of the biogenetic
      origin of flavan derivatives as well as chemical synthesis of this class of
      compounds. Various nucleophilic units could be introduced to the C(4) position
      via the S(N) 1-type substitution, and orthogonal activation of two distinct
      flavan units enabled block assembly of linear catechin oligomers. These
      methodologies would serve as a reliable way to supply valuable, homogeneuous
      samples for biological testing.

PMID- 21898782
TI  - Mycosis fungoides following pityriasis lichenoides: an exceptional event or a
      potential evolution.

PMID- 21898783
TI  - Refractory pediatric nonrhabdomyosarcoma soft tissue sarcoma associated with
      ectopic production of beta hCG and hypercalcemia induced by PTHrP.
AB  - A 3-month-old male with a mass on the right side of his back was admitted to our
      hospital. The tumor was a pathologically high-grade nonrhabdomyosarcoma soft
      tissue sarcoma (NRSTS). Treatment included subtotal tumor resection followed by
      chemotherapy. Elevation of serum beta hCG and hypercalcemia with detection of
      PTHrP was associated with tumor progression. The tumor was refractory to
      multiagent chemotherapy, and the patient died of the disease at 22 months of age.
      This case is novel in demonstrating a beta hCG secreting refractory NRSTS.

PMID- 21898784
TI  - Oral arsenic trioxide for relapsed acute promyelocytic leukemia in pediatric
      patients.
AB  - Four patients (age 3-11 years at diagnosis) with relapsed acute promyelocytic
      leukemia (APL), 12-38 months from diagnosis, were treated with oral arsenic
      trioxide (As(2) O(3) ). One patient was treated with oral As(2) O(3) monotherapy
      and chemotherapy. Three patients failed initial oral or intravenous As(2) O(3)
      monotherapy were treated with oral As(2) O(3) plus ATRA followed by long-term
      oral maintenance (cumulative As(2) O(3) dose 280-2,100 mg). All patients achieved
      molecular remission, at a median follow up of 122 (10-132) months with no adverse
      effects. Oral As(2) O(3) , particularly in prolonged maintenance with oral ATRA
      may obviate the need of stem cell transplantation in relapsed pediatric APL.

PMID- 21898785
TI  - Children with ITP: looking beyond the platelet count.

PMID- 21898786
TI  - Chorioallantoic and yolk sac placentation in Thrichomys laurentinus (Echimyidae)
      and the evolution of hystricognath rodents.
AB  - The evolutionary history of Hystricognathi is associated with major
      transformations in their placental system. Data so far indicate that key
      characters are independent from size dimensions in medium to very large species.
      To better understand the situation in smaller species, we analyzed placental
      development in a spiny rat, Thrichomys laurentinus. Fourteen individuals ranging
      from early implantation to near term were investigated by histology,
      immunohistochemistry, proliferation activity and electron microscopy.
      Placentation in Thrichomys revealed major parallels to the guinea pig and other
      hystricognath rodents with respect to the early and invasive implantation, the
      process of trophoblast invasion, the internal organization of the labyrinth and
      the trophospongium as well as the establishment of the complete inverted yolk sac
      placenta. In contrast to systematically related small-sized species, the
      placental regionalization in Thrichomys was characterized by a remarkable
      lobulated structure and associated growing processes. Reverse to former
      perspectives, these conditions represented ancient character states of
      hystricognaths. The subplacenta was temporarily supplied by both the maternal and
      fetal blood systems, a rare condition among hystricognaths. The extraplacental
      trophoblast originating from the subplacenta was partly proliferative in mid
      gestation. In conclusion, the presented results indicated that only minor
      variations occurred in small-sized hystricognath species, independent of their
      systematic interrelationships. Previous views were supported that placentation in
      hystricognaths followed an extraordinary stable pattern, although the group had
      distinct habitats in South America and Africa that were separated 30-40 million
      years ago.

PMID- 21898787
TI  - The place of development in mathematical evolutionary theory.
AB  - Development plays a critical role in structuring the joint offspring-parent
      phenotype distribution. It thus must be part of any truly general evolutionary
      theory. Historically, the offspring-parent distribution has often been treated in
      such a way as to bury the contribution of development, by distilling from it a
      single term, either heritability or additive genetic variance, and then working
      only with this term. I discuss two reasons why this approach is no longer
      satisfactory. First, the regression of expected offspring phenotype on parent
      phenotype can easily be nonlinear, and this nonlinearity can have a pronounced
      impact on the response to selection. Second, even when the offspring-parent
      regression is linear, it is nearly always a function of the environment, and the
      precise way that heritability covaries with the environment can have a
      substantial effect on adaptive evolution. Understanding these complexities of the
      offspring-parent distribution will require understanding of the developmental
      processes underlying the traits of interest. I briefly discuss how we can
      incorporate such complexity into formal evolutionary theory, and why it is likely
      to be important even for traits that are not traditionally the focus of evo-devo
      research. Finally, I briefly discuss a topic that is widely seen as being
      squarely in the domain of evo-devo: novelty. I argue that the same conceptual and
      mathematical framework that allows us to incorporate developmental complexity
      into simple models of trait evolution also yields insight into the evolution of
      novel traits.

PMID- 21898788
TI  - Linking the molecular evolution of avian beta (beta) keratins to the evolution of
      feathers.
AB  - Feathers of today's birds are constructed of beta (beta)-keratins, structural
      proteins of the epidermis that are found solely in reptiles and birds.
      Discoveries of "feathered dinosaurs" continue to stimulate interest in the
      evolutionary origin of feathers, but few studies have attempted to link the
      molecular evolution of their major structural proteins (beta-keratins) to the
      appearance of feathers in the fossil record. Using molecular dating methods, we
      show that before the appearance of Anchiornis (~155 Million years ago (Ma)) the
      basal beta-keratins of birds began diverging from their archosaurian ancestor
      ~216 Ma. However, the subfamily of feather beta-keratins, as found in living
      birds, did not begin diverging until ~143 Ma. Thus, the pennaceous feathers on
      Anchiornis, while being constructed of avian beta-keratins, most likely did not
      contain the feather beta-keratins found in the feathers of modern birds. Our
      results demonstrate that the evolutionary origin of feathers does not coincide
      with the molecular evolution of the feather beta-keratins found in modern birds.
      More likely, during the Late Jurassic, the epidermal structures that appeared on
      organisms in the lineage leading to birds, including early forms of feathers,
      were constructed of avian beta-keratins other than those found in the feathers of
      modern birds. Recent biophysical studies of the beta-keratins in feathers support
      the view that the appearance of the subfamily of feather beta-keratins altered
      the biophysical nature of the feather establishing its role in powered flight.

PMID- 21898789
TI  - Ventral nerve cord in Phoronopsis harmeri larvae.
AB  - The nervous system organization is considered a phylogenetically important
      character among metazoans. The phylum Phoronida is included in a supraphyletic
      taxon known as Lophotrochozoa. Many lophotrochozoans possess a metameric ventral
      nerve cord as adults or larvae. Phoronids do not exhibit external metamery either
      as larvae or as adults. The current study describes the ventral nerve cord in the
      young larva of Phoronopsis harmeri. This structure is apparent both in the
      serotonergic and FMRF-amidergic nervous system in young larvae. The ventral nerve
      cord extends from the mouth to the tentacular ridge. Both serotonergic and FMRF
      amidergic components consist of two ventrolateral nerves, each with several
      unipolar neurons. The ventrolateral nerves connect to each other by means of thin
      repetitive transversal nerves ("commissures"). The abundance of neurons and
      nerves in the epidermis of the oral field of actinotrocha larva likely reflects
      the importance of this area in collection of food particles. The ventral nerve
      cords of the actinotrocha and the metatrochophore differ in their positions with
      respect to ciliated bands: the cord is located between the preoral and postoral
      ciliated bands in the actinotrocha but between the postoral ciliated band and
      telotroch in the metatrochophore. The presence of the ventral nerve cord, which
      contains repetitive elements (neurons and "commissures"), in the early
      development of P. harmeri may recapitulate some stages of nervous system
      development during phoronid phylogeny. The larval nervous system does not contain
      nervous centers under the tentacular ridge that can correlate with the
      catastrophic metamorphosis and unique body plan of phoronids.

PMID- 21898791
TI  - In vitro anti-platelet effects of simple plant-derived phenolic compounds are
      only found at high, non-physiological concentrations.
AB  - SCOPE: Bioactive polyphenols from fruits, vegetables, and beverages have anti
      platelet effects and may thus affect the development of cardiovascular disease.
      We screened the effects of 26 low molecular weight phenolic compounds on two in
      vitro measures of human platelet function. METHODS AND RESULTS: After platelets
      had been incubated with one of 26 low molecular weight phenolic compounds in
      vitro, collagen-induced human platelet aggregation and in vitro TRAP-induced P
      selectin expression (as marker of platelet activation) were assessed. Incubation
      of platelet-rich plasma from healthy volunteers with 100 MUmol/L hippuric acid,
      pyrogallol, catechol, or resorcinol significantly inhibited collagen-induced
      platelet aggregation (all p<0.05; n>=15). Incubation of whole blood with
      concentrations of 100 MUmol/L salicylic acid, p-coumaric acid, caffeic acid,
      ferulic acid, 4-hydroxyphenylpropionyl glycine, 5-methoxysalicylic acid, and
      catechol significantly inhibited TRAP-induced surface P-selectin expression (all
      p<0.05; n=10). Incubation with lower concentrations of phenolics affected neither
      platelet aggregation nor activation. CONCLUSION: As concentrations of 100 MUmol/L
      are unlikely to be reached in the circulation, it is doubtful whether consumption
      of dietary phenolics in nutritionally attainable amounts plays a major role in
      inhibition of platelet activation and aggregation in humans.

PMID- 21898793
TI  - Novel silicon nanohemisphere-array solar cells with enhanced performance.

PMID- 21898790
TI  - Comparative genomics of duplicate gamma-glutamyl transferase genes in teleosts:
      medaka (Oryzias latipes), stickleback (Gasterosteus aculeatus), green spotted
      pufferfish (Tetraodon nigroviridis), fugu (Takifugu rubripes), and zebrafish
      (Danio rerio).
AB  - The availability of multiple teleost (bony fish) genomes is providing
      unprecedented opportunities to understand the diversity and function of gene
      duplication events using comparative genomics. Here we examine multiple
      paralogous genes of gamma-glutamyl transferase (GGT) in several distantly related
      teleost species including medaka, stickleback, green spotted pufferfish, fugu,
      and zebrafish. Through mining genome databases, we have identified multiple GGT
      orthologs. Duplicate (paralogous) GGT sequences for GGT1 (GGT1 a and b), GGTL1
      (GGTL1 a and b), and GGTL3 (GGTL3 a and b) were identified for each species.
      Phylogenetic analysis suggests that GGTs are ancient proteins conserved across
      most metazoan phyla and those paralogous GGTs in teleosts likely arose from the
      serial 3R genome duplication events. A third GGTL1 gene (GGTL1c) was found in
      green spotted pufferfish; however, this gene is not present in medaka,
      stickleback, or fugu. Similarly, one or both paralogs of GGTL3 appear to have
      been lost in green spotted pufferfish, fugu, and zebrafish. Syntenic
      relationships were highly maintained between duplicated teleost chromosomes,
      among teleosts and across ray-finned (Actinopterygii) and lobe-finned
      (Sarcopterygii) species. To assess subfunction partitioning, six medaka GGT genes
      were cloned and assessed for developmental and tissue-specific expression. On the
      basis of these data, we propose a modification of the "duplication-degeneration
      complementation" model of subfunction partitioning where quantitative differences
      rather than absolute differences in gene expression are observed between gene
      paralogs. Our results demonstrate that multiple GGT genes have been retained
      within teleost genomes. Questions remain, however, regarding the functional roles
      of multiple GGTs in these species.

PMID- 21898794
TI  - Polymeric nanopillars reinforced with metallic shells in the lower stem region.

PMID- 21898792
TI  - Self-assembly and microstructural control of a hexa-peri-hexabenzocoronene
      perylene diimide dyad by solvent vapor diffusion.

PMID- 21898795
TI  - Protein-based memristive nanodevices.

PMID- 21898796
TI  - Separation of alkaloids from herbs using high-speed counter-current
      chromatography.
AB  - Alkaloids represent a most widespread group of bioactive natural products.
      Because of their alkalinity and structural diversity, the fractionation and
      purification of the alkaloids from herbs can often present a number of practical
      difficulties using the conventional chromatographic techniques. High-speed
      counter-current chromatography (HSCCC) is a liquid-liquid partition
      chromatography with a support-free liquid stationary phase, and is gaining more
      and more popularity as a viable separation technique for bioactive compounds from
      natural resources. In the present review, focus is placed on the separation of
      alkaloids by both conventional HSCCC and pH-zone-refining counter-current
      chromatography (CCC) techniques from herbs. The review presents the separation of
      over 120 different alkaloid compounds from more than 30 plant species by the
      conventional HSCCC and pH-zone-refining CCC. Based on the data from the
      literature, the proper solvent systems for the separation of alkaloids by the
      conventional HSCCC and pH-zone-refining CCC are also summarized.

PMID- 21898797
TI  - Focused ultrasound solid-liquid extraction and selective pressurised liquid
      extraction to determine bisphenol A and alkylphenols in sewage sludge by gas
      chromatography-mass spectrometry.
AB  - A new method for determining endocrine disrupter compounds (EDCs) in sewage
      sludge is described in this paper. EDCs studied were bisphenol A (BPA) and
      alkylphenols (APs). In order to obtain a fast and simple method, selective
      pressurised liquid extraction (SPLE) and focused ultrasound solid-liquid
      extraction (FUSLE) were tested. Best results for SPLE were obtained using
      Florisil as clean-up sorbent and dichloromethane as extraction solvent, while
      temperature was the only significant variable. Analyte extraction by SPLE was
      completed in only one extraction cycle of 1 min at 130  degrees C. FUSLE was
      carried out in one step of 20 s at 75% power (0.5 cycles) and with 8 mL of ethyl
      acetate. Although the optimised FUSLE process was faster, simpler and cheaper,
      SPLE provided higher recovery values (ranging from 81 to 105%) and therefore SPLE
      based method was selected and validated. The SPLE and GC-MS method showed an LOD
      of 10.7 ng/g for BPA and LODs between 1.2 and 41.6 ng/g for APs. Relative
      standard deviation values lower than 6% were obtained for all analytes. As a
      result, an efficient, fast and simple method based on SPLE and GC-MS for the
      determination of BPA and APs in sewage sludge is proposed.

PMID- 21898798
TI  - Development and evaluation of a spiral tube column for counter-current
      chromatography.
AB  - An improved type-J counter-current chromatography (CCC) planet centrifuge with
      two spiral tube columns (volume 2*15 mL, beta value 0.3-0.7, tubing 0.8 mm id)
      was developed and evaluated for its retention ability of four typical different
      solvent systems including heptane-methanol (1:1, v/v) (A), hexane-ethyl acetate
      methanol-water (1:1:1:1, v/v) (B), n-butanol-acetic acid-water (4:1:5, v/v) (C),
      PEG1000-K(2)HPO(4)-water (12.5:12.5:75, w/w) (D) under eight different operation
      modes. The results indicated that the spiral tube column could significantly
      increase the retention of four typical solvent systems compared with a
      traditional multilayer coil column with similar parameters (volume 35 mL, beta
      value 0.3-0.7, tubing 0.8 mm id). The retention of stationary phase (S(f)) for
      the less polar system (A) and moderately polar solvent system (B) can be
      increased by about 10%, and for the polar system (C) and aqueous two-phase system
      (ATPS) (D) by 30-40%. The preliminary applications of this spiral tube column to
      the separation of small molecular compounds such as moderately polar theaflavins,
      polar anthocyanins and dipeptides were successful. Acceptable resolution can be
      obtained between cytochrome c and myoglobin, lysozyme and myoglobin when it was
      applied on protein separation; however, it still needs to be improved with regard
      to its column efficiency.

PMID- 21898799
TI  - Detection and expression analysis of recombinant proteins in plant-derived
      complex mixtures using nanoUPLC-MS(E).
AB  - The use of mass spectrometry to identify recombinant proteins that are expressed
      in total soluble proteins (TSPs) from plant extracts is necessary to accelerate
      further processing steps. For example, the method consists of TSP sample
      preparation and trypsin digestion prior to the preliminary characterization using
      nanoUPLC-MS(E) analysis of the recombinant proteins that are expressed in TSP
      samples of transgenic soybean seeds. A TSP sample as small as 50 MUg can be
      effectively analyzed. In this study, transgenic soybean seeds that expressed
      recombinant cancer testis antigen (CTAG) were used. The procedure covered 30% of
      the protein sequence and was quantified at 0.26 ng, which corresponded to 0.1% of
      the TSP sample. A comparative proteomic profile was generated by the comparison
      of a negative control and sample that showed a unique expression pattern of CTAG
      in a transgenic line. The experimental data from the TSP extraction, sample
      preparation and data analysis are discussed herein.

PMID- 21898800
TI  - Synthesis and application of clindamycin succinate as a novel chiral selector for
      capillary electrophoresis.
AB  - A novel chiral selector, clindamycin succinate, was synthesized and first used as
      a chiral selector in capillary electrophoresis (CE). The chiral resolution
      ability of this kind of clindamycin derivation was studied by CE using some
      racemic drugs as model analytes. From the experimental results, it was found that
      both resolution and selectivity of the selector were dependent on the following
      parameters: concentration of chiral selectors, pH of the running buffer,
      temperature of the capillary column, applied voltage and organic modifier used.
      The results show that the chiral selector possesses high resolution toward some
      racemic drugs, including ofloxacin, chlorphenamine, tryptophan, propranolol,
      sotalol and metoprolol. Excellent chiral resolution of these tested drugs was
      achieved under the optimal conditions of 50 mM clindamycin succinate, 10% MeOH
      v/v, 50 mM Tris buffer, pH 4.0, at 22 kV and 20  degrees C within 25 min.

PMID- 21898801
TI  - Molecularly imprinted solid-phase extraction coupled with HPLC for the selective
      determination of monobutyl phthalate in bottled water.
AB  - A molecularly imprinted polymer (MIP) was prepared using monobutyl phthalate as
      template. The synthesis was optimized by using different porogens and functional
      monomers. The MIP was used as a selective sorbent in molecularly imprinted solid
      phase extraction (MIP-SPE) for pre-concentration and determination of monobutyl
      phthalate (mBP) from the bottled water. The difference in recognition selectivity
      of the polymer columns was observed in HPLC system, and the effect of the mobile
      phase on the performance of MIP columns was also investigated. Control of the MIP
      SPE process is seen as important in helping to facilitate the selective
      extraction of mBP from water samples. Thereafter, the choice of washing solvent,
      eluting solvent amount, pH of loading sample, flow rate of loading solution and
      the loading sample volume was presented. The optimized procedure was described as
      follows: 25 mL spiked aqueous solution was percolated through the MIP-SPE
      cartridge at the flow rate of 1.5 mL/min. After rinsing with
      acetonitrile/methanol mixture (1:1, v/v), the bound analyte was desorbed with 3
      mL methanol. The developed MIP-SPE method was demonstrated to be applicable for
      the analysis of mBP in the bottled water.

PMID- 21898802
TI  - Rapid simultaneous determination of isoflavones in Radix puerariae using high
      performance liquid chromatography-triple quadrupole mass spectrometry with novel
      shell-type column.
AB  - A high-performance liquid chromatography (HPLC) coupled with triple quadrupole
      mass spectrometry (MS/MS) method was developed for rapid determination of 13
      isoflavones in Radix puerariae. A novel shell-type column, namely Kinetex core
      shell C(18) column (50 mm*2.1 mm id, 2.6 MUm), and gradient elution were used
      during the analysis. The chromatographic peaks of 13 investigated compounds were
      identified by comparing their retention time and MS data with the related
      reference compounds. Multiple-reaction monitoring (MRM) was employed for the
      quantitative analysis with negative ionization mode. All calibration curves
      showed good linearity (r(2)>0.9990) within test ranges. The LOD and LOQ were
      lower than 0.017 and 0.873 MUg/mL on column, respectively. The intra- and inter
      day precisions for 13 analytes were <1.17 and 2.17%, respectively, and the
      recoveries were 93.1-104.4%. The validated method was applied for quantitative
      analysis of 13 isoflavones in 7 species of Radix puerariae. The result
      demonstrated that HPLC-MS/MS system with Kinetex column could be a promising
      analytical tool for the determination of isoflavones in traditional Chinese
      medicines, which is helpful for comprehensive evaluation of quality of R.
      puerariae.

PMID- 21898803
TI  - Simple and sensitive determination of low-molecular-mass aromatic aldehydes in
      swimming pool water by LC-diode array detector.
AB  - This work reports the development of a simple method for the quantitative
      determination of aromatic and aliphatic low-molecular-mass aldehydes (LMMAs) as
      disinfection by-products (DBPs) in indoor swimming pool waters after chlorination
      with a simplified SPE sample treatment. The method is based on the continuous in
      situ derivatization/preconcentration of the aldehydes with 2,4
      dinitrophenylhydrazine (DNPH) on a Lichrolut EN column in the presence of beta
      CD. After elution, the 2,4-dinitrophenylhydrazine derivatives were separated on
      an RP-C(18) analytical column using gradient of ACN-water at 60-80%. The
      optimized sample treatment described here allowed the direct analysis of large
      volumes of water in order to improve the sensitivity of the method; LODs in the
      60-120 ng/L range were achieved for aromatic LMMAs by using a volume of 50 mL of
      water, precision being 7.5% or better at a concentration level of 5 MUg/L. These
      results indicate that the ensuing method is a useful choice for the determination
      of LMMAs in water samples that provides better results than reported LC
      alternatives in terms of the LOD (except for MS/MS detection), sample
      requirements for analysis and cost.

PMID- 21898804
TI  - Feasibility of ultra high performance supercritical neat carbon dioxide
      chromatography at conventional pressures.
AB  - The implementation of columns packed with sub-2 MUm particles in supercritical
      fluid chromatography (SFC) is described using neat carbon dioxide as the mobile
      phase. A conventional supercritical fluid chromatograph was slightly modified to
      reduce extra column band broadening. Performances of a column packed with 1.8 MUm
      C18-bonded silica particles in SFC using neat carbon dioxide as the mobile phase
      were compared with results obtained in ultra high performance liquid
      chromatography (UHPLC) using a dedicated chromatograph. As expected and usual in
      SFC, higher linear velocities than in UHPLC must be applied in order to reach
      optimal efficiency owing to higher diffusion coefficient of solutes in the mobile
      phase; similar numbers of theoretical plates were obtained with both techniques.
      Very fast separations of hydrocarbons are presented using two different alkyl
      bonded silica columns.

PMID- 21898805
TI  - Estimation of dermal and oral exposure of children to scented toys: analysis of
      the migration of fragrance allergens by dynamic headspace GC-MS.
AB  - Fragrances capable of inducing contact allergy in skin potentially can migrate
      from the toy to the child via oral or dermal contacts. The goal of this work was
      the developing of an analytical method based on dynamic headspace GC-MS to
      determine the concentration of 24 fragrances in saliva or sweat simulant. Under
      optimized conditions, 5 mL of the migration simulant with 2 g sodium chloride
      were incubated for 10 min at 30 degrees C. The headspace was purged at a flow
      rate of 50 mL/min. The compounds were quantified by internal calibration
      resulting in good linearity (>0.991). The recovery was greater than 66.3% for
      most of the compounds. The limits of detection ranged between 0.5 ng/mL for
      hydrophobic and 196.0 ng/mL for hydrophilic fragrances. The method was
      subsequently applied to seven real toys purchased from the market. The highest
      migration rate could be observed for benzyl benzoate with 268.0 ng/cm(2)/min.
      Based on the migration data measured, the ranges of dermal and oral exposure of
      children to fragrances in scented toys were calculated. The maximum oral and
      dermal exposure levels were estimated at 22.2 MUg per kg body weight (BW) and day
      (d) for benzyl benzoate and 605.0 MUg/kg BW/d for benzyl alcohol, respectively.

PMID- 21898806
TI  - Screening vasoconstriction inhibitors from traditional Chinese medicines using a
      vascular smooth muscle/cell membrane chromatography-offline-liquid chromatography
      mass spectrometry.
AB  - We developed an analytical method for screening vasoconstriction inhibitors from
      traditional Chinese medicines (TCMs) by combining vascular smooth muscle/cell
      membrane chromatography (VSM/CMC) with liquid chromatography-tandem mass
      spectrometry (LC-MS/MS). Primary cultured VSM cells from rat thoracic aortas were
      used for preparation of the stationary phase of the VSM/CMC column. Retention
      fractions from the VSM/CMC column were collected and then analyzed by LC-MS/MS
      under the optimized conditions offline. The suitability and reliability of the
      VSM/CMC-offline-LC-MS/MS method was assessed using nitrendipine and nifedipine as
      positive controls, and this method was then applied to screen vasodilator
      components from the extracts of Fructus Schisandrae Chinensis (FSC) and Fructus
      Schisandrae Sphenantherae (FSS). The major components from both species retained
      by VSM/CMC were identified as deoxyschizandrin (DSD) and schisantherin A (STA) by
      LC-MS/MS. Competition experiments indicated that DSD and nifedipine bound
      competitively to membrane receptors, while DSD and STA had partly overlapping
      binding sites on VSM-cell membranes. In vitro pharmacological trials confirmed
      that STA and DSD could dose-dependently relax the rat thoracic aortas pre
      contracted by KCl. Our VSM/CMC-offline-LC-MS/MS method can be applied for
      screening vasoconstriction inhibitors from TCMs collected from FSC and FSS, and
      may be useful in the development of vasodilators from natural products.

PMID- 21898807
TI  - Comparison of capillary electrophoretic techniques for analysis and
      characterization of metallothioneins.
AB  - To explore and understand the significance of individual metallothionein
      isoforms, the methods of their identification are needed. Separation of these
      isoforms requires a high resolution technique which can exploit very small
      differences in mass, charge, and hydrophobicity. In this report, three different
      techniques of CE were analyzed and used for metallothionein separation: detection
      using capillary gel electrophoresis, capillary zone electrophoresis, and
      capillary isoelectric focusing. Also, three different metallothionein samples
      were used from horse kidney, rabbit liver, and human liver. We identified
      metallothionein isoforms based on the determination of their relative molecular
      masses, on the charge differences in different pH buffers, and based on the pI
      value. Methods used in this report allow metallothionein identification, permit
      to quantify the purity and content of its isoforms, and allow studying its
      polymerization. This report supports and endorses the increased application of CE
      methodology in proteomics.

PMID- 21898808
TI  - Optimization of simultaneous derivatization and extraction of aliphatic amines in
      water samples with dispersive liquid-liquid microextraction followed by HPLC.
AB  - Dispersive liquid-liquid microextraction based on solidification of floating
      organic droplet (DLLME-SFO) with simultaneous derivatization followed by high
      performance liquid chromatography-diode array detection (HPLC-DAD) was applied
      for preconcentration and determination of primary and secondary aliphatic amines
      in environmental water samples. A ternary mixture consisting of a disperser, an
      extractant and a derivatization reagent was used for the simultaneous
      derivatization and extraction of aliphatic amines in different water samples. The
      effects of various experimental parameters on derivatization and extraction
      efficiency were studied simultaneously using experimental design. A Plackett
      Burman design was performed for screening of variables in order to determine the
      significant variables affecting the extraction efficiency. Then, the significant
      factors were optimized by using a Box-Behnken design (BBD) and the response
      surface equations were derived. Under optimal conditions, the preconcentration
      factors were between 210 and 290. The limit of detections (LODs) ranged from
      0.005 to 0.02 MUg/L and dynamic linear ranges (DLRs) of 0.05-500 and 0.1-500
      MUg/L were obtained for most of analytes. The performance of the method was
      evaluated for extraction and determination of primary and secondary aliphatic
      amines in environmental water samples in micrograms per liter and satisfactory
      results were obtained (RSDs <12.5%).

PMID- 21898809
TI  - Selective enrichment of glycopeptides for mass spectrometry analysis using C18
      fractionation and titanium dioxide chromatography.
AB  - Comprehensive glycoprotein characterization based on mass spectrometry (MS) is
      challenging because of low concentration of glycopeptides and suppression effect
      of abundant non-glycosylated peptides in MS. Therefore, it is vital to enrich
      glycopeptides before MS analysis. A new method was developed to selectively
      enrich glycopeptides from complex sample by coupling C18 fractionation with
      titanium dioxide (TiO(2)) enrichment. The new method allows to selectively enrich
      N-linked glycopeptides with various glycan forms and different sequence lengths.
      Compared with single TiO(2) method, the established method demonstrated higher
      glycopeptide selectivity and higher glycosylation heterogeneity coverage. Further
      application of this method to mixture of non-glycosylated protein and
      glycoprotein digests at different levels reveals the feasibility of enrichment of
      tryptic glycopeptides from simple proteomics samples.

PMID- 21898810
TI  - An integrated enzyme-linked immunosorbent assay system with an organic light
      emitting diode and a charge-coupled device for fluorescence detection.
AB  - A fluorescence detection system for a microfluidic device using an organic light
      emitting diode (OLED) as the excitation light source and a charge-coupled device
      (CCD) as the photo detector was developed. The OLED was fabricated on a glass
      plate by photolithography and a vacuum deposition technique. The OLED produced a
      green luminescence with a peak emission at 512 nm and a half bandwidth of 55 nm.
      The maximum external quantum efficiency of the OLED was 7.2%. The emission
      intensity of the OLED at 10 mA/cm(2) was 13 MUW (1.7 mW/cm(2)). The fluorescence
      detection system consisted of the OLED device, two band-pass filters, a five
      microchannel poly(dimethylsiloxane) (PDMS) microfluidic device and a linear CCD.
      The fluorescence detection system was successfully used in a flow-based enzyme
      linked immunosorbent assay on a PDMS microfluidic device for the rapid
      determination of immunoglobulin A (IgA), a marker for human stress. The detection
      limit (S/N=3) for IgA was 16.5 ng/mL, and the sensitivity was sufficient for
      evaluating stress. Compared with the conventional 96-well microtiter plate assay,
      the analysis time and the amounts of reagent and sample solutions could all be
      reduced.

PMID- 21898811
TI  - LC-MS/MS profiling for detection of endogenous steroids and prostaglandins in
      tissue samples.
AB  - Roles of steroid hormones, and compounds that can influence their levels in
      cells, are of increasing interest in e.g. cancer research, partly because
      resistance to hormone therapies often complicates treatment. To elucidate the
      processes involved, the hormones and related compounds need to be accurately
      measured. Reversed-phase liquid chromatography with dynamic multiple reaction
      monitoring mass spectrometric detection in electrospray mode is capable of
      providing such measurements. Therefore, LC-MS/MS was developed for sensitive,
      selective analysis of 11 steroid hormones, cholesterol and two prostaglandins.
      The effects of the tissue matrix, and solid-phase extraction (SPE) sample clean
      up, on the LC-MS/MS signals of the hormones were also investigated. The results
      show that the developed LC-MS/MS method, following SPE clean-up to reduce matrix
      interference, can detect selected steroids in extracts of mouse tissues. The
      method provides linear measurements of the steroids at concentrations up to few
      ng/MUL, and limits of detection in the range 0.03-0.2 pg/MUL (for some compounds
      lower than those of previously reported methods).

PMID- 21898812
TI  - Quantitative determination of bovine caseinoglycomacropeptide in infant formulas
      by ultra-high-performance liquid chromatography-electrospray-ionization mass
      spectrometry.
AB  - An ultra-high-performance liquid chromatography-electrospray ionization coupled
      to mass spectrometry method has been developed for determining
      caseinoglycomacropeptide (CGMP) in infant formulas by selected ion reaction and
      area monitoring modes. The present study focused on the optimization of sample
      pretreatment, chromatographic resolution and mass spectrometry parameters. After
      a simple sample pretreatment, the two genetic variants of
      caseinoglycomacropeptide, CGMP(A) and CGMP(B), were separated using a BEH300
      C(18) column by gradient elution. The established method was extensively
      validated by determining the linearity (R(2)>0.999), average recovery (95.8
      118.4%), inter-day precision (relative standard deviation <=7.81%) and intra-day
      precision (relative standard deviation <=6.99%) based on two scan modes. To
      further verify the applicability of the method, 21 brands of commercial available
      infant formulas were analyzed. The results showed that the present method is
      selective, sensitive and reliable for separating and quantifying two genetic
      variants (CGMP(A) and CGMP(B)) of caseinoglycomacropeptide in infant formulas
      with complex matrix.

PMID- 21898813
TI  - Preparation and evaluation of molecularly imprinted microspheres for solid-phase
      extraction of 1,4-hydroxybenzoic acid esters in soy.
AB  - Molecularly imprinted microspheres (MIMs) were prepared by precipitation
      polymerization for the binding and recognition of 1,4-hydroxybenzoic acid esters.
      Ethyl p-hydroxybenzoate (EtPHB) was used as the template molecule, methacrylic
      acid as the functional monomer, ethylene dimethacrylate as the linking agent. It
      was evaluated by solid-phase extraction column packed with MIMs combined with
      liquid chromatography to determine trace preservatives including benzoic acid,
      methyl p-hydroxybenzoate, EtPHB, propyl p-hydroxybenzoate in food products. A
      solid-phase extraction based on MIM procedure was used to isolate four additives
      from the food matrix before quantitative analysis. The Scatchard plot suggested
      that the template-polymer system had two-site binding behavior with the
      dissociation constants of 0.3577 and 3.952 mg/g, respectively. The rebinding
      test, based on the molecularly imprinted solid-phase extraction column technique,
      showed the recoveries of soy samples spiked with four additives within 88.4
      110.6%, with the relative standard deviations of 1.97-3.82%. Finally, the method
      was successfully applied for the analysis of parabens in foodstuff without
      traditional pretreatment.

PMID- 21898814
TI  - Characterization of cyclofructan-based chiral stationary phases by linear free
      energy relationship.
AB  - Cyclofructans (CFs), a new class of chiral selectors, have been recently
      introduced for application in liquid chromatography and capillary
      electrophoresis. So far, derivatized CFs have performed interesting separation
      possibilities for a variety of compounds. The current work is focused on
      characterization of three different CF-based chiral stationary phases (CF-based
      CSPs), i.e. isopropyl carbamate cyclofructan 6 (IP-CF6), R-naphthylethyl
      carbamate cyclofructan 6 (RN-CF6) and dimethylphenyl carbamate cyclofructan 7
      (DMP-CF7). The linear free energy relationship (LFER) model was used to reveal
      the dominant interactions participating in the complex retention mechanism. A set
      of 44 different test solutes, with known solvation parameters, was used to
      determine the regression coefficients of the LFER equation under two mobile-phase
      compositions in normal separation mode. The LFER results showed that hydrogen
      bond acidity, hydrophobicity and dipolarity/polarizibility mostly affect the
      retention and separation process on the CF-based columns in the studied
      separation systems.

PMID- 21898815
TI  - Effects of freeze-drying of samples on metabolite levels in metabolome analyses.
AB  - Freeze-drying (FD) is a useful technique for removing water from biological
      tissues, such as food samples. Cellular components freeze at once, and the ice
      sublimates under conditions of high vacuum and low temperatures. Because
      biological activity is restricted during FD, the degradation of cellular
      metabolites is often believed to be limited. However, the cellular structure is
      damaged by several factors, such as the increase in cell volume during freezing,
      and this has serious effects on the levels of some cellular metabolites. We
      studied these effects of FD on metabolite levels when using it as a sample
      preparation step in metabolome analysis. We observed significant decreases in the
      levels of some metabolites, such as succinate and choline, in Arabidopsis and
      pear, respectively. We also found that the effects of FD on certain metabolite
      levels differed between Arabidopsis plants and pear fruits. These results suggest
      that it is necessary to confirm the metabolite recovery in each sample species
      when FD is used for sample preparation.

PMID- 21898816
TI  - A new HPLC method with fluorescence detection for the determination of memantine
      in human plasma.
AB  - A sensitive, selective, simple and fast HPLC method based on the formation of
      derivative with fluorescamine was developed for the determination of memantine
      (ME) in human plasma. Separation was achieved on a CN column (200 mm*4.6 mm)
      using acetonitrile-10 mM orthophosphoric acid containing 1 mL/L triethylamine
      (45:55, v/v) at a flow rate of 1 mL/min. Emission and excitation wavelengths were
      480 and 380 nm, respectively. Amantadine was used as an internal standard.
      Calibration graphs were rectilinear over the range of 1.0-100.0 ng/mL. Limit of
      detection and limit of quantification were found to be 0.3 and 1.0 ng/mL,
      respectively. Intra-day and inter-day relative standard deviation values were
      found to be <2.03%. Average recovery was also found to be around 94%. Proposed
      method was applied for the pharmacokinetic study in a healthy volunteer after a
      single oral administration of 20 mg of ME.

PMID- 21898817
TI  - Application of centrifugal precipitation chromatography and high-speed counter
      current chromatography equipped with a spiral tubing support rotor for the
      isolation and partial characterization of carotenoid cleavage-like enzymes in
      Enteromorpha compressa (L.) Nees.
AB  - Centrifugal precipitation chromatography and a high-speed counter-current
      chromatography system equipped with a spiral tubing support rotor (spHSCCC) were
      successfully applied for the identification and isolation of carotenoid cleavage
      like enzymes from Enteromorpha compressa (L.) Nees. This is the first study
      separating active enzymes from a complex natural matrix by spHSCCC. The target
      enzymes were identified after fractionation of the proteins in an acetone Tris
      buffer gradient by centrifugal precipitation chromatography. Also, an aqueous two
      phase solvent system consisting of PEG 1000 and mono- and dibasic potassium
      phosphate was used for the isolation of the enzymes by spHSCCC. The purified
      fractions contained two proteins of 65 and 72 kDa, respectively. The enzymes
      could cleave beta-carotene and beta-apo-8'-carotenal to produce beta-ionone.

PMID- 21898818
TI  - Determination of polyphenols in three Capsicum annuum L. (bell pepper) varieties
      using high-performance liquid chromatography-tandem mass spectrometry: their
      contribution to overall antioxidant and anticancer activity.
AB  - A mixture of polyphenol components was isolated from the fruits of C. annuum L.
      cv. Cupra, C. annuum L. cv. Orange glory, and C. annuum L. cv. ST4712 (CLST), via
      70% methanol extraction followed by column chromatography over silica gel. The
      polyphenol components of the mixture were analyzed via HPLC-MS/MS and compared
      with the reported data. Three cinnamic acid derivatives and five flavonoid
      components in the fruits of the three varieties were identified for the first
      time in this study. The antioxidant activity and anticancer effect of the
      polyphenol mixtures of the three fruits were determined. The antioxidant and
      anticancer activities of CLST were substantially higher than those of C. annuum
      L. cv. Cupra and C. annuum L. cv. Orange glory. The high activities of CLST were
      attributed to the much higher concentration of quercetin derivatives in CLST.

PMID- 21898819
TI  - New hierarchically porous titania monoliths for chromatographic separation media.
AB  - Separation media based on hierarchically porous titania (TiO(2)) monoliths for
      high-performance liquid chromatography (HPLC) have been successfully fabricated
      by the sol-gel process of titanium alkoxide in a mild condition utilizing a
      chelating agent and mineral salt. The as-gelled TiO(2) monoliths were subjected
      to a simple solvent exchange process from ethanol (EtOH) to H(2)O followed by
      drying and calcination. The resultant monolithic TiO(2) columns consist of
      anatase crystallites with the typical specific surface area of more than 200
      m(2)/g. The resultant monolithic TiO(2) column calcined at 200 and 400 degrees C
      exhibited a good separation performance for organophosphates as well as for polar
      benzene derivatives in the normal-phase mode.

PMID- 21898820
TI  - SAHA Capture Compound--a novel tool for the profiling of histone deacetylases and
      the identification of additional vorinostat binders.
AB  - Suberoylanilide hydroxamic acid (SAHA) is a potent histone deacetylase (HDAC)
      inhibitor. Inhibitors of HDACs are used in cancer therapy based on the role HDACs
      play in transcription by regulating chromatin compaction and non-histone proteins
      such as transcription factors. Profiling of HDAC expression is of interest in the
      functional proteomics analysis of cancer. Also, non-HDAC proteins may interact
      with HDAC inhibitor drugs and contribute to the drug mode of action. We here
      present a tool for the unbiased chemical proteomic profiling of proteins that
      specifically interact with SAHA. We designed and synthesized a trifunctional
      Capture Compound containing SAHA as selectivity and identified HDACs1, 2, 3 and
      6, known and predicted HDAC interactors from human-derived HepG2 cell lysate, as
      well as a set of new potential non-HDAC targets of SAHA. One of these non-HDAC
      targets, isochorismatase domain-containing protein 2 (ISOC2) is putative
      hydrolase associated with the negative regulation of the tumor-suppressor
      p16(INK4a). We demonstrated the direct and dose-dependent interaction of SAHA to
      the purified recombinant ISOC2 protein. Using SAHA Capture Compound mass
      spectrometry, we thus identified potential new SAHA target proteins in an
      entirely unbiased chemical proteomics approach.

PMID- 21898822
TI  - An improved method for the construction of decoy peptide MS/MS spectra suitable
      for the accurate estimation of false discovery rates.
AB  - The relevance of libraries of annotated MS/MS spectra is growing with the amount
      of proteomic data generated in high-throughput experiments. These reference
      libraries provide a fast and accurate way to identify newly acquired MS/MS
      spectra. In the context of multiple hypotheses testing, the control of the number
      of false-positive identifications expected in the final result list by means of
      the calculation of the false discovery rate (FDR). In a classical sequence search
      where experimental MS/MS spectra are compared with the theoretical peptide
      spectra calculated from a sequence database, the FDR is estimated by searching
      randomized or decoy sequence databases. Despite on-going discussion on how
      exactly the FDR has to be calculated, this method is widely accepted in the
      proteomic community. Recently, similar approaches to control the FDR of spectrum
      library searches were discussed. We present in this paper a detailed analysis of
      the similarity between spectra of distinct peptides to set the basis of our own
      solution for decoy library creation (DeLiberator). It differs from the previously
      published results in some key points, mainly in implementing new methods that
      prevent decoy spectra from being too similar to the original library spectra
      while keeping important features of real MS/MS spectra. Using different proteomic
      data sets and library creation methods, we evaluate our approach and compare it
      with alternative methods.

PMID- 21898821
TI  - Proteomic analysis of oligodendrogliomas expressing a mutant isocitrate
      dehydrogenase-1.
AB  - Gliomas are primary tumors of the human central nervous system with unknown
      mechanisms of progression. Isocitrate dehydrogenase-1 (IDH1) mutation is frequent
      in diffuse gliomas such as oligodendrogliomas. To gain insights into the
      physiopathology of oligodendrogliomas that have a better prognosis than other
      diffuse gliomas, we combined microdissection, 2-D DIGE and MS/MS focusing on
      proteome alterations associated with IDH1 mutation. We first compared tumor
      tissues (TT) and minimally infiltrated parenchymal tissues (MIT) of four IDH1
      mutated oligodendrogliomas to verify whether proteins specific to
      oligodendroglioma tumor cells could be identified from one patient to another.
      This study resulted in identification of 68 differentially expressed proteins,
      with functions related to growth of tumor cells in a nervous parenchyma. We then
      looked for proteins distinctly expressed in TT harboring either mutant
      (oligodendrogliomas, n=4) or wild-type IDH1 (oligodendroglial component of
      malignant glio-neuronal tumors, n=4). This second analysis resulted in
      identification of distinct proteome patterns composed of 42 proteins.
      Oligodendrogliomas with a mutant IDH1 had noteworthy enhanced expression of
      enzymes controlling aerobic glycolysis and detoxification, and anti-apoptosis
      proteins. In addition, the mutant IDH1 migrated differently from the wild-type
      IDH1 form. Comparative proteomic analysis might thus be suitable to identify
      proteome alterations associated with a well-defined mutation.

PMID- 21898823
TI  - Large-scale N-glycoproteome map of rat brain tissue: simultaneous
      characterization of insoluble and soluble protein fractions.
AB  - The large-scale N-glycosylation analysis is critical for biomedical research,
      since a variety of diseases are found to be associated with glycoproteins. By a
      combination of glycoprotein analysis in insoluble protein fraction solubilized
      with 1% v/v 1-butyl-3-methylimidazolium tetrafluoroborate (BMIM BF(4)) and those
      in soluble fraction, a total number of 462 non-redundant N-glycoprotein groups,
      including 316 transmembrane glycoproteins, were successfully identified.
      Correspondingly, 849 unique N-glycosites were confidently recognized. The data
      set could provide a support for the further in-depth research of brain N
      glycosylation, such as for the discovery of candidate drug targets and
      biomarkers.

PMID- 21898825
TI  - UniCarbKB: putting the pieces together for glycomics research.
AB  - Despite the success of several international initiatives the glycosciences still
      lack a managed infrastructure that contributes to the advancement of research
      through the provision of comprehensive structural and experimental glycan data
      collections. UniCarbKB is an initiative that aims to promote the creation of an
      online information storage and search platform for glycomics and glycobiology
      research. The knowledgebase will offer a freely accessible and information-rich
      resource supported by querying interfaces, annotation technologies and the
      adoption of common standards to integrate structural, experimental and functional
      data. The UniCarbKB framework endeavors to support the growth of
      glycobioinformatics and the dissemination of knowledge through the provision of
      an open and unified portal to encourage the sharing of data. In order to achieve
      this, the framework is committed to the development of tools and procedures that
      support data annotation, and expanding interoperability through cross-referencing
      of existing databases. Database URL: http://www.unicarbkb.org.

PMID- 21898824
TI  - Differential profiling studies of N-linked glycoproteins in glioblastoma cancer
      stem cells upon treatment with gamma-secretase inhibitor.
AB  - We have recently demonstrated that Notch pathway blockade by gamma-secretase
      inhibitor (GSI) depletes cancer stem cells (CSCs) in Glioblastoma Multiforme
      (GBM) through reduced proliferation and induced apoptosis. However, the detailed
      mechanism by which the manipulation of Notch signal induces alterations on post
      translational modifications such as glycosylation has not been investigated.
      Herein, we present a differential profiling work to detect the change of
      glycosylation pattern upon drug treatment in GBM CSCs. Rapid screening of
      differential cell surface glycan structures has been performed by lectin
      microarray on live cells followed by the detection of N-linked glycoproteins from
      cell lysates using multi-lectin chromatography and label-free quantitative mass
      spectrometry analysis. A total of 51 and 52 glycoproteins were identified in the
      CSC- and GSI-treated groups, respectively, filtered by a combination of decoy
      database searching and Trans-Proteomic Pipeline (TPP) processing. Although no
      significant changes were detected from the lectin microarray experiment, 7
      differentially expressed glycoproteins with high confidence were captured after
      the multi-lectin column including key enzymes involved in glycan processing.
      Functional annotations of the altered glycoproteins suggest a phenotype
      transformation of CSCs toward a less tumorigenic form upon GSI treatment.

PMID- 21898826
TI  - Protein recovery and identification from the gulf killifish, Fundulus grandis:
      comparing snap-frozen and RNAlater(r) preserved tissues.
AB  - Reliable proteomic analysis of biological tissues requires sampling approaches
      that preserve proteins as close to their in vivo state as possible. In the
      current study, the patterns of protein abundance in one-dimensional (1-D) gels
      were assessed for five tissues of the gulf killifish, Fundulus grandis, following
      snap-freezing tissues in liquid nitrogen or immersion of fresh tissues in
      RNAlater((r)). In liver and heart, the protein profiles in 1-D gels were better
      preserved by snap-freezing, while in gill, the 1-D protein profile was better
      preserved by immersion in RNAlater((r)). In skeletal muscle and brain, the two
      approaches yielded similar patterns of protein abundance. LC-MS/MS analyses and
      database searching resulted in the identification of 17 proteins in liver and 12
      proteins in gill. Identified proteins include enzymes of energy metabolism,
      structural proteins, and proteins serving other biological functions. These
      protein identifications for a species without a sequenced genome demonstrate the
      utility of F. grandis as a model organism for environmental proteomic studies in
      vertebrates.

PMID- 21898827
TI  - Beneficial compaction of spinal cord lesion by migrating astrocytes through
      glycogen synthase kinase-3 inhibition.
AB  - The migratory response of astrocytes is essential for restricting inflammation
      and preserving tissue function after spinal cord injury (SCI), but the mechanisms
      involved are poorly understood. Here, we observed stimulation of in vitro
      astrocyte migration by the new potent glycogen synthase kinase-3 (GSK-3)
      inhibitor Ro3303544 and investigated the effect of Ro3303544 administration for 5
      days following SCI in mice. This treatment resulted in accelerated migration of
      reactive astrocytes to sequester inflammatory cells that spared myelinated fibres
      and significantly promoted functional recovery. Moreover, the decreased extent of
      chondroitin sulphate proteoglycans and collagen IV demonstrated that scarring was
      reduced in Ro3303544-treated mice. A variety of in vitro and in vivo experiments
      further suggested that GSK-3 inhibition stimulated astrocyte migration by
      decreasing adhesive activity via reduced surface expression of beta1-integrin.
      Our results reveal a novel benefit of GSK-3 inhibition for SCI and suggest that
      the stimulation of astrocyte migration is a feasible therapeutic strategy for
      traumatic injury in the central nervous system.

PMID- 21898828
TI  - Evolution of SR protein and hnRNP splicing regulatory factors.
AB  - The splicing of pre-mRNAs is an essential step of gene expression in eukaryotes.
      Introns are removed from split genes through the activities of the spliceosome, a
      large ribonuclear machine that is conserved throughout the eukaryotic lineage.
      While unicellular eukaryotes are characterized by less complex splicing, pre-mRNA
      splicing of multicellular organisms is often associated with extensive
      alternative splicing that significantly enriches their proteome. The alternative
      selection of splice sites and exons permits multicellular organisms to modulate
      gene expression patterns in a cell type-specific fashion, thus contributing to
      their functional diversification. Alternative splicing is a regulated process
      that is mainly influenced by the activities of splicing regulators, such as SR
      proteins or hnRNPs. These modular factors have evolved from a common ancestor
      through gene duplication events to a diverse group of splicing regulators that
      mediate exon recognition through their sequence-specific binding to pre-mRNAs.
      Given the strong correlations between intron expansion, the complexity of pre
      mRNA splicing, and the emergence of splicing regulators, it is argued that the
      increased presence of SR and hnRNP proteins promoted the evolution of alternative
      splicing through relaxation of the sequence requirements of splice junctions.

PMID- 21898830
TI  - ApoTome to visualize E-cadherin and p63 expression in oral pre-cancer.
AB  - Precise histopathological localization of E-cadherin and p63 is of immense
      importance in understanding the integrity of oral mucosal stratified epithelium
      in normal and diseased conditions. Necessarily immunohistochemical imaging should
      have minimum bleaching impact on the dyes and ability to produce clear and crisp
      images. Here ApoTome provides an alternative with metal halide light source and
      structured illumination under the assistance of grids, along with integrated
      image processing modality to generate crisp images with digital interface. The
      current study demonstrates the applicability of such microscopic system in
      capturing fluorescence images of immunohistochemical sections of normal and
      precancerous biopsies in respect to the expression of p63 and E-cadherin in the
      epithelial cells. The ApoTome images localize the nuclear and membranous
      expressions of p63 and E-cadherin, respectively, with remarkable specificity. The
      findings on E-cadherin expression have enormous diagnostic significance as these
      images clearly differentiate the early and advanced stages of oral submucous
      fibrosis based on their cytoplasmic and membranous location. Thus, this study
      clearly depicts a remarkable performance of ApoTome with diagnostic significance.

PMID- 21898829
TI  - Aging--RNA in development and disease.
AB  - Given that RNA is involved in virtually all biological processes, it is perhaps
      not surprising that several RNA-binding proteins are associated with aging and
      with different age-related disorders. Other articles in this volume will discuss
      some specific examples of diseases where RNA plays a role that are also
      associated with aging, such as cancer and inflammation, so here I will discuss
      some general aspects of how RNA changes with the aging process. I will also
      discuss some specific examples of RNA-binding proteins that are associated with
      age-dependent neurological diseases as these provide an interesting framework to
      examine how lifetime mutations might lead to a late onset disease, although the
      answers to these questions are still not well understood.

PMID- 21898831
TI  - G-PKDrep-live, a genetically encoded FRET reporter to measure PKD activity at the
      trans-Golgi-network.
AB  - The serine/threonine protein kinase D (PKD) is recruited to the trans-Golgi
      network (TGN) by interaction with diacylglycerol (DAG) and Arf1 and promotes the
      fission of vesicles containing cargo destined for the plasma membrane. PKD
      activation is mediated by PKC(-induced phosphorylation. However, signaling
      pathways that activate PKD specifically at the TGN are only poorly characterized.
      Recently we created G-PKDrep, a genetically encoded fluorescent reporter for PKD
      activity at the TGN in fixed cells. To establish a reporter useful for monitoring
      Golgi-specific PKD activity in living cells we now refined G-PKDrep to generate G
      PKDrep-live. Specifically, phosphorylation of G-PKDrep-live expressed in
      mammalian cells results in changes of fluorescence resonance energy transfer
      (FRET), and allows for indirect imaging of PKD activity. In a proof-of-principle
      experiment using phorbolester treatment, we demonstrate the reporter's capability
      to track rapid activation of PKD at the TGN. Furthermore, activation-induced FRET
      changes are reversed by treatment with PKD-specific pharmacological inhibitors.
      Thus, the newly developed reporter G-PKDrep-live is a suitable tool to visualize
      dynamic changes in PKD activity at the TGN in living cells. See accompanying
      commentary by Gautam DOI: 10.1002/biot.201100424.

PMID- 21898832
TI  - Identification and characterization of inhibitors of the aminoglycoside
      resistance acetyltransferase Eis from Mycobacterium tuberculosis.

PMID- 21898834
TI  - Runaway ROS as a selective anticancer strategy.

PMID- 21898835
TI  - Colloidal templating fabrication of aluminum-organophosphonate films using high
      molecular weight PS-b-PEO.
AB  - High molecular weight polystyrene-block-poly(ethylene oxide) diblock copolymer
      (PS-b-PEO) is utilized as colloidal spheres in the presence of water. Adequately
      thick films with multilayers of spherical macropores are fabricated in one-pot
      under highly concentrated conditions of PS-b-PEO. The frameworks are constructed
      using aluminum organophosphonate as a complicated hybrid component. The
      macropores (30-200 nm) are homogeneously distributed over the entire films and
      pore windows between the macropores are tunable (up to nearly 10 nm) by changing
      the relative amount of PS-b-PEO in the precursor solutions.

PMID- 21898833
TI  - Halogen bonding at the active sites of human cathepsin L and MEK1 kinase:
      efficient interactions in different environments.
AB  - In two series of small-molecule ligands, one inhibiting human cathepsin L (hcatL)
      and the other MEK1 kinase, biological affinities were found to strongly increase
      when an aryl ring of the inhibitors is substituted with the larger halogens Cl,
      Br, and I, but to decrease upon F substitution. X-ray co-crystal structure
      analyses revealed that the higher halides engage in halogen bonding (XB) with a
      backbone C=O in the S3 pocket of hcatL and in a back pocket of MEK1. While the S3
      pocket is located at the surface of the enzyme, which provides a polar
      environment, the back pocket in MEK1 is deeply buried in the protein and is of
      pronounced apolar character. This study analyzes environmental effects on XB in
      protein-ligand complexes. It is hypothesized that energetic gains by XB are
      predominantly not due to water replacements but originate from direct
      interactions between the XB donor (Caryl-X) and the XB acceptor (C=O) in the
      correct geometry. New X-ray co-crystal structures in the same crystal form (space
      group P2(1)2(1)2(1)) were obtained for aryl chloride, bromide, and iodide ligands
      bound to hcatL. These high-resolution structures reveal that the backbone C=O
      group of Gly61 in most hcatL co-crystal structures maintains water solvation
      while engaging in XB. An aryl-CF3-substituted ligand of hcatL with an
      unexpectedly high affinity was found to adopt the same binding geometry as the
      aryl halides, with the CF3 group pointing to the C=O group of Gly61 in the S3
      pocket. In this case, a repulsive F2C-F???O=C contact apparently is energetically
      overcompensated by other favorable protein-ligand contacts established by the CF3
      group.

PMID- 21898836
TI  - Metal-organic niccolite: synthesis, structures, phase transition, and magnetic
      properties of [CH3NH2(CH2)2NH2CH3][M2(HCOO)6] (M=divalent Mn, Fe, Co, Ni, Cu and
      Zn).
AB  - We report the synthesis, crystal structures, thermal and magnetic
      characterizations of a family of metal-organic frameworks adopting the niccolite
      (NiAs) structure, [dmenH(2)(2+)][M(2)(HCOO)(6)(2-)] (dmen=N,N'
      dimethylethylenediamine; M=divalent Mn, 1Mn; Fe, 2Fe; Co, 3Co; Ni, 4Ni; Cu, 5Cu;
      and Zn, 6Zn). The compounds could be synthesized by either a diffusion method or
      directly mixing reactants in methanol or methanol-water mixed solvents. The five
      members, 1Mn, 2Fe, 3Co, 4Ni, and 6Zn are isostructural and crystallize in the
      trigonal space group P31c, while 5Cu crystallizes in C2/c. In the structures, the
      octahedrally coordinated metal ions are connected by anti-anti formate bridges,
      thus forming the anionic NiAs-type frameworks of [M(2)(HCOO)(6)(2-)], with
      dmenH(2)(2+) located in the cavities of the frameworks. Owing to the Jahn-Teller
      effect of the Cu(2+) ion, the 3D framework of 5Cu consists of zigzag Cu-formate
      chains with Cu-OCHO-Cu connections through short basal Cu-O bonds, further linked
      by the long axial Cu-O bonds. 6Zn exhibits a phase transition probably as a
      result of the order-disorder transition of the dmenH(2)(2+) cation around 300 K,
      confirmed by differential scanning calorimetry and single crystal X-ray
      diffraction patterns under different temperatures. Magnetic investigation reveals
      that the four magnetic members, 1Mn, 2Fe, 3Co, and 4Ni, display spin-canted
      antiferromagnetism, with a Neel temperature of 8.6 K, 19.8 K, 16.4 K, and 33.7 K,
      respectively. The Mn, Fe, and Ni members show spin-flop transitions below 50 kOe.
      2Fe possesses a large hysteresis loop with a large coercive field of 10.8 kOe.
      The Cu member, 5Cu, shows overall antiferromagnetism (both inter- and intra
      chains) with low-dimensional characteristics.

PMID- 21898837
TI  - Synthetic beta-K(0.33)V2O5 nanorods: a metal-insulator transition in vanadium
      oxide bronze.
AB  - We found a linear relationship between the metal-insulator transition (MIT)
      temperature and the A(+) ionic radius of the beta-A(0.33)V(2)O(5) bronze family,
      leading our attention to beta-K(0.33)V(2)O(5) which has been neglected for a long
      time. We have introduced a facile hydrothermal method to obtain the single
      crystalline beta-K(0.33)V(2)O(5) nanorods. As expected, both the temperature
      dependence of the resistivity and magnetization demonstrated MITs at about 72 K
      for beta-K(0.33)V(2)O(5), thus matching well with the linear relationship
      described above. The beta-K(0.33)V(2)O(5) was assigned as a new member of the
      beta-A(0.33)V(2)O(5) bronze family for their similar crystal and electronic
      structures and their MIT property; this addition enriches the beta
      A(0.33)V(2)O(5) bronze family.

PMID- 21898838
TI  - Organo- and hydrogelators based on luminescent monocationic terpyridyl
      platinum(II) complexes with biphenylacetylide ligands.
AB  - A series of phosphorescent terpyridyl platinum(II) complexes with ancillary
      biphenylacetylide ligands, namely, [(R(3)tpy)PtC=C(biphenyl)]X (R=tBu, H, or
      Et(2)N; tpy=2,2';6',2''-terpyridyl; X is an anion) were synthesized and
      structurally characterized by various spectroscopic techniques and X-ray
      diffraction methods. Despite a lack of long alkyl chain(s) or hydrogen-bonding
      motif(s), complexes [(tpy)PtC=C(biphenyl)]Cl and [(tBu(3)tpy)PtC=C(biphenyl)]X
      (X=Cl, ClO(4), PF(6), or BF(4)) were found to gelate water and organic solvents,
      respectively. The self-aggregation of these complexes in solutions and the
      resulting gels were investigated with variable-temperature (VT) (1)H NMR
      spectroscopy, polarized optical microscopy, and absorption/emission spectroscopy.
      SEM micrographs on dry gels revealed entangled nanofibers with diameters of 20-40
      nm and lengths of tens of micrometers. Powder X-ray diffraction (PXRD) study
      revealed various degrees of crystallinity of these fibrillar nanostructures. The
      substituents on both the terpyridyl and acetylide ligands and counterion of these
      complexes play a profound but concerted role in tuning the intermolecular
      metal...metal and/or pi-pi interactions, and hence the gelation properties.

PMID- 21898839
TI  - Iron-catalyzed C-H bond activation for the ortho-arylation of aryl pyridines and
      imines with Grignard reagents.
AB  - Direct arylation of the ortho-C-H bond of an aryl pyridine or an aryl imine with
      an aryl Grignard reagent has been achieved by using an iron-diamine catalyst and
      a dichloroalkane as an oxidant in a short reaction time (e.g., 5 min) under mild
      conditions (0  degrees C). The use of an aromatic co-solvent, such as
      chlorobenzene and benzene, and slow addition of the Grignard reagent are
      essential for the high efficiency of the reaction. The present arylation reaction
      has distinct merits over the previously developed reaction that used an arylzinc
      reagent, such as its reaction rate and atom economy. Selective C-H bond
      activation occurs in the presence of a leaving group, such as a tosyloxy, chloro,
      and bromo group. Studies on a stoichiometric reaction and kinetic isotope effects
      shed light on the reaction intermediate and the C-H bond-activation step.

PMID- 21898840
TI  - Construction of polymer-protein bioconjugates with varying chain topologies:
      polymer molecular weight and steric hindrance effects.
AB  - We report on the fabrication of well-defined polymer-protein bioconjugates with
      varying chain architectures, including star polymers, star block copolymers, and
      heteroarm star copolymers through the specific noncovalent interaction between
      avidin and biotinylated synthetic polymer precursors. Homopolymer and diblock
      precursors site-specifically labeled with a single biotin moiety at the chain
      terminal, chain middle, or diblock junction point were synthesized by a
      combination of atom-transfer radical polymerization (ATRP) and click reactions.
      By taking advantage of molecular recognition between avidin and biotin moieties,
      supramolecular star polymers, star block copolymers, and heteroarm star
      copolymers were successfully fabricated. This specific binding process was also
      assessed by using the diffraction optic technology (DOT) technique. We further
      investigated the effects of polymer molecular weights, location of biotin
      functionality within the polymer chain, and polymer chain conformations, that is,
      steric hindrance effects, on the binding numbers of biotinylated polymer chains
      per avidin within the polymer-protein bioconjugates, which were determined by the
      standard avidin/2-(4-hydroxyazobenzene)benzoic acid (HABA) assay. The binding
      numbers vary in the range of 1.9-3.3, depending on the molecular weights,
      locations of biotin functionality within synthetic polymer precursors, and
      polymer chain conformations.

PMID- 21898841
TI  - Seed-mediated growth of gold inside hollow silica nanospheres for sensing
      peroxide and glucose concentrations.

PMID- 21898842
TI  - Applying small molecule microarrays and resulting affinity probe cocktails for
      proteome profiling of mammalian cell lysates.
AB  - Small molecule microarrays (SMMs) are proving to be increasingly important tools
      for assessing protein-ligand interactions, as well as in screening for enzyme
      substrates and inhibitors, in a high-throughput manner. We previously described
      an SMM-facilitated screening strategy for the rapid identification of probes
      against gamma-secretase, an aspartic protease. In this article, we extend upon
      this work with an expanded library of hydroxyethylamine-derived inhibitors which
      non-exclusively target aspartic proteases. Our library is diversified across
      P(2), P(1), P(1)', and P(2)' positions. Accordingly, 86 new inhibitors are
      synthesized using a combinatorial, solid-phase synthetic approach, bringing the
      total library size to 284-biotinylated compounds, which were arrayed onto avidin
      slides. In order to elucidate enzymatic activity and profiles within complex
      biological samples, screening is performed using fluorescently-labeled mammalian
      cell lysates. This yielded reproducible profiles or binding fingerprints that
      correspond with interactions from aspartic proteases or accessory proteins as
      well as other interacting targets that were present in the sample. The brightest
      microarray hits were converted to affinity-based probes (AfBPs) using convenient,
      1-step "click" chemistry with benzophenone from the relevant building blocks.
      Pull-down/mass spectrometric analysis with these probes (individuals or cocktail)
      yielded putative protein targets that include well-known aspartic proteases, such
      as cathepsin D which is a clear marker for breast cancer cell lines, T47D. Many
      other hits were also identified, which may be secondary or tertiary interactors
      of aspartic proteases, or yet unreported off-targets of the hydroxyethylamine
      pharmacophore. Our work herein thus provides a candidate list of biomarkers for
      further investigations. Taken together, this SMM-facilitated strategy for the
      discovery of new AfBPs should provide a useful tool for high-throughput
      development of novel small molecule probes and the identification of new aspartic
      proteases as well as related biomarkers in the future.

PMID- 21898843
TI  - Comparison of bipolar hosts and mixed-hosts as host structures for deep-blue
      phosphorescent organic light emitting diodes.

PMID- 21898844
TI  - [Re(CO)3Cl]-chelation-mediated electronic coupling between two amine redox sites
      through the 5,5'-positions of 2,2'-bipyridine.
AB  - The electronic coupling between two amine redox sites bridged through the 5,5'
      positions of the [Re(CO)(3)Cl]-chelated 2,2'-bipyridine was studied by the
      electrochemical, spectroscopic, and EPR analysis. Interestingly, multiple near
      infrared bands were observed in this new organic mixed-valent system. The results
      are interpreted with the aid of DFT and TDDFT calculations.

PMID- 21898845
TI  - Palladium-catalyzed alkynylthiolation of alkynes with triisopropylsilylethynyl
      sulfide.

PMID- 21898846
TI  - The Korean Chemical Society: launching society for ChemConnect, ChemConsort, and
      ChemCongress in the International Year of Chemistry.

PMID- 21898847
TI  - First evidence of a cDNA encoding for a melatonin receptor (mel 1b) in brain,
      retina, and testis of Pelophylax esculentus.
AB  - Melatonin, nocturnally secreted by the pineal gland, regulates a variety of
      physiological functions, including reproduction. Here, we investigated the
      evidence of melatonin binding sites in frog tissue (brain, retina, and testis)
      through saturation and competition binding experiments. In the frog, Pelophylax
      esculentus, our results confirm the presence of a single class of melatonin
      specific binding sites in the brain and retina, but not in the testis. Further
      experiments have been done using biomolecular approaches (PCR analysis). Here, we
      report the isolation of a cDNA encoding for a melatonin receptor type (mel 1b)
      from brain, retina, and testis of the P. esculentus. PCR analysis revealed that
      melatonin expression is higher in the brain and retina, whereas it is lower in
      the testis. The presence of a melatonin receptor transcript in the frog testis
      corroborates our previous results obtained in in vitro experiments that suggest
      that melatonin might act directly in male vertebrate gonads, and indicates that
      the frog testis may be a suitable model to verify the role of indolamine in
      testicular activity.

PMID- 21898848
TI  - Effects of immune activation and glucocorticoid administration on feather growth
      in greenfinches.
AB  - Elevation of glucocorticoid (GC) hormone levels is an integral part of stress
      response (as well as its termination) and immunomodulation. These hormones are
      also responsible for mobilizing energy stores by stimulation of gluconeogenesis
      and inhibition of protein synthesis. Elevation of GCs is thus incompatible with
      other protein-demanding processes, such as moult. Previous studies have shown
      that chronic elevation of GC hormones suppresses feather growth. Here, we asked
      whether similar effect would also occur in the case of acute GC elevation and
      induction of an inflammatory response by foreign antigen. We performed an
      experiment on captive wild-caught greenfinches (Carduelis chloris) injecting
      birds with phytohaemagglutinin (PHA) and dexamethasone (DEX) in a factorial
      design. To assess the possible somatic impacts of these manipulations, we removed
      one of the outermost tail feathers before the experiment and measured mass and
      rachis diameter and length of the replacement feathers grown in captivity.
      Immunostimulation by PHA reduced rachis length, but did not affect feather mass
      or rachis diameter. Single injection of a synthetic GC hormone DEX significantly
      reduced all three parameters of feather size. Altogether, these findings
      demonstrate the sensitivity of feather growth to manipulation of immune and
      adrenal functions. Our results corroborate the somatic costs of immune activation
      and suggest that even a short-term elevation of GC hormones may induce long-term
      somatic costs with a potential impact on fitness. Our findings also imply that a
      single injection of DEX, frequently used as a diagnostic tool, can have lasting
      effects and researchers must consider this when designing experiments.

PMID- 21898849
TI  - Ovarian development of a river catfish Hemibagrus nemurus (Valenciennes, 1840) in
      captivity.
AB  - Hemibagrus nemurus is a riverine catfish with high economic and nutritive values.
      Investigations on ovarian development of this fish were carried out to determine
      the mode of ovarian development and describe the oocyte developmental stages.
      Histological studies were done on ovaries using light microscopy and scanning
      electron microscopy. Fish were sampled monthly for a period of six months (August
      2009 to January 2010). The mean oocyte diameter (OD) ranged from 871 +/- 161.41
      um to 1,167 +/- 26.77 um and the highest OD was in November. Oocyte size
      frequency distribution showed a polymodal distribution. The mean gonadosomatic
      index (GSI) ranged from 1.14 +/- 0.87% to 7.06 +/- 1.40% and highest GSI was in
      November. The ovaries exhibited three phases of oocyte growth, which were primary
      growth, secondary growth and maturation phases. Based on histological criteria,
      the oocyte developmental stages were divided into seven stages as chromatin
      nucleolar, early perinucleolar, late perinucleolar, cortical alveolar,
      vitellogenesis, mature oocyte and germinal vesicle migration stages. All the
      seven stages of oocyte development were observed in the ovaries. Oogonia were
      always present throughout the developmental stages. The ovaries had more than two
      stages of oocyte development. This is the first report on the mode of ovarian
      development of H. nemurus. These findings indicated that H. nemurus has
      asynchronous mode of ovarian development and is capable of spawning several times
      in a year under favourable conditions.

PMID- 21898850
TI  - Aerobic dive limit does not decline in an aging pinniped.
AB  - Apneustic hunters such as diving mammals exploit body oxygen stores while
      submerged; therefore, any decline in oxygen handling at advanced life stages
      could critically impair foraging ability. We calculated the aerobic dive limit
      (cADL = 17.9 +/- 4.4  min SD) from blood and muscle oxygen stores and published
      metabolic rates of Weddell seals within (9-16 years, n = 24) and beyond peak
      reproductive age (17-27 years, n = 26), to investigate (1) senescent constraints
      in apneustic hunting, and (2) whether mass or age primarily determines oxygen
      stores and ADL in older seals. We compared cADL with behavioral ADL from 5,275
      free-ranging dives (bADL = 24.0 +/- 5.3 min, n = 18 females). We observed no
      changes in Weddell seal oxygen stores, its determinants, or in ADLs late in life.
      Oxygen stores were better predicted by mass than age, consistent with published
      findings for young adults. Hematological panels (n = 6) were consistent across
      mass and age, though hematocrit (females > males, 6% elevation) and mean
      corpuscular hemoglobin content (females < males, 8% reduction) varied by sex.
      Whole blood viscosity was decreased with increasing mass in females and was
      higher than in males overall (+18%). This was largely due to elevated hematocrit
      in females, although plasma viscosity also varied under some conditions. Females
      had higher blood volume and elevated blood oxygen stores (vol% body mass), which
      did not translate into significantly higher cADL (18.1 vs. 17.1 min for males).
      Neither cADL nor bADL were mass- or age-dependent.

PMID- 21898851
TI  - Negative effects of yolk testosterone and ticks on growth in canaries.
AB  - Maternal yolk hormones in bird eggs are thought to adjust the offspring to the
      post-hatching environment. This implies that the effects of maternal yolk
      hormones should vary with the post-hatching environment, but to date such context
      dependency has largely been ignored. We experimentally increased yolk
      testosterone concentrations in canary eggs and simultaneously manipulated the
      post-hatching context via an experimental tick-infestation of the chicks. This
      allows us to evaluate the context-dependency of hormone-mediated maternal
      effects, as it has previously been shown that ectoparasites alter the maternal
      yolk androgen deposition. The experimental tick infestation reduced growth in
      chicks from sham-treated eggs, indicating harmful effects of this ectoparasite in
      canaries. Chicks from testosterone-treated eggs were not affected in their
      development by ticks, suggesting lower ectoparasite vulnerability. But this may
      also be due to the fact that experimentally elevated yolk testosterone levels
      impaired growth even under parasite-free conditions. This contrasts previous
      studies, but these studies often manipulated first laid eggs, while we used eggs
      of subsequent laying positions. Later laid eggs are presumably of lower quality
      and contain higher yolk testosterone concentrations. Thus, the effects of
      elevated yolk testosterone on growth may be dose-dependent or vary with the egg
      quality, suggesting prenatal context-dependency.

PMID- 21898853
TI  - Microglial regulation of cholinergic differentiation in the basal forebrain.
AB  - Because inflammation during pregnancy can lead to neurodevelopmental anomalies,
      we investigated the role of inflamed microglia on cholinergic precursors in the
      rat embryonic basal forebrain (BF) cultured on embryonic day 15. Conditioned
      medium (CM) taken from microglia stimulated variously (microglial CM; MCM)
      increased activity of choline acetyltransferase (ChAT), the enzyme responsible
      for acetylcholine biosynthesis and a phenotypic hallmark of the cholinergic
      neuron. There was a concomitant decline in glutamic acid decarboxylase
      expression. Of stimulators tested, only beta-amyloid failed to produce effective
      MCM. Infection with a Lac-Z-containing retrovirus revealed that MCM promoted
      cholinergic differentiation from undifferentiated precursors in the population.
      Several candidates were tested for their ability to mimic MCM. Mature nerve
      growth factor (NGF) did not mimic MCM, but acted synergistically with it to
      promote enormous increases in ChAT activity. However, a microglial cell line
      produced high-molecular weight forms of NGF (pro-NGF) that were lethal to mature
      cholinergic neurons. Although bone morphogenetic proteins (BMP) 2, 4, and 9
      increased ChAT activity dose-dependently, noggin did not inhibit the effects of
      the MCM, suggesting that BMPs were not the only active factor(s) in the MCM.
      Embryonic microglia isolated following maternal inflammation produced a variety
      of immune system cytokines and chemokines. One of these, interleukin-6 (IL-6),
      was tested for its ability to promote cholinergic differentiation. Although IL-6
      alone did not mimic the action of MCM, neutralization of it inhibited MCM
      effectiveness. Thus, following maternal inflammation, a complex microglial
      derived cocktail of factors can promote excess cholinergic differentiation in the
      embryonic BF.

PMID- 21898852
TI  - The ever-changing brain: cellular and molecular mechanisms for the effects of
      stressful experiences.
AB  - The adult brain is capable of considerable structural and functional plasticity
      and the study of hormone actions in brain has contributed to our understanding of
      this important phenomenon. In particular, stress and stress-related hormones such
      as glucocorticoids and mineralocorticoids play a key role in the ability of acute
      and chronic stress to cause reversible remodeling of neuronal connections in the
      hippocampus, prefrontal cortex, and amygdala. To produce this plasticity, these
      hormones act by both genomic and non-genomic mechanisms together with ongoing,
      experience-driven neural activity mediated by excitatory amino acid
      neurotransmitters, neurotrophic factors such as brain derived neurotrophic
      factor, extracellular molecules such as neural cell adhesion molecule,
      neuropeptides such as corticotrophin releasing factor, and endocannabinoids. The
      result is a dynamic brain architecture that can be modified by experience. Under
      this view, the role of pharmaceutical agents, such as antidepressants, is to
      facilitate such plasticity that must also be guided by experiences.

PMID- 21898855
TI  - Extracellular matrix and perineuronal nets in CNS repair.
AB  - A perineuronal net (PNN) is a layer of lattice-like matrix which enwraps the
      surface of the soma and dendrites, and in some cases the axon initial segments,
      in sub-populations of neurons in the central nervous system (CNS). First reported
      by Camillo Golgi more than a century ago, the molecular structure and the
      potential role of this matrix have only been unraveled in the last few decades.
      PNNs are mainly composed of hyaluronan, chondroitin sulfate proteoglycans, link
      proteins, and tenascin R. The interactions between these molecules allow the
      formation of a stable pericellular complex surrounding synapses on the neuronal
      surface. PNNs appear late in development co-incident with the closure of critical
      periods for plasticity. They play a direct role in the control of CNS plasticity,
      and their removal is one way in which plasticity can be re-activated in the adult
      CNS. In this review, we examine the molecular components and formation of PNNs,
      their role in maturation and synaptic plasticity after CNS injury, and the
      possible mechanisms of PNN action.

PMID- 21898854
TI  - Extracellular matrix and the neural stem cell niche.
AB  - Basal lamina is present in many stem cell niches, but we still have a poor
      understanding of the role of this and other extracellular matrix (ECM)
      components. Here, we review current knowledge regarding ECM expression and
      function in the neural stem cell niche, focusing on the subependymal zone of the
      adult CNS. An increasing complexity of ECM molecules has been described, and a
      number of receptors expressed on the stem cells identified. Experiments
      perturbing the niche using genetics or cytotoxic ablation of the rapidly dividing
      precursors, or using explant culture models to examine specific growth factors,
      have been influential in showing how changes in these ECM receptors might
      regulate neural stem cell behavior. However the role of changes in the matrix
      itself remains to be determined. The answers will be important, as they will
      point to the molecules required to engineer niches ex-vivo so as to provide tools
      for regenerative neuroscience.

PMID- 21898856
TI  - Introduction: the role of extracellular matrix in nervous system development and
      maintenance.

PMID- 21898858
TI  - The analysis of the transcriptome as a new approach for biomarker development to
      trace the abuse of anabolic steroid hormones.
AB  - The abuse of anabolic steroid hormones in human sports and animal husbandry is an
      ubiquitous problem and therefore a tight control program in both areas is very
      important. Within these control programs, hormone residues are detected by
      immunoassays or chromatographical methods in combination with mass spectrometry.
      With these methods, all known substances can be detected; yet new xenobiotic
      growth promoters and new ways of application are difficult to detect. Therefore
      it is important to develop new sensitive screening methods to enable an efficient
      control for misused anabolic substances. The detection of their physiological
      action is a promising approach. Anabolic steroid hormones directly influence the
      expression of specific genes and thus the analysis of the transcriptome of
      different target tissues and matrices is of great interest. This review describes
      our recent efforts made concerning the analysis of gene expression changes in
      different tissues, different species and under different anabolic treatments.

PMID- 21898859
TI  - Improved partial least squares models for stability-indicating analysis of
      mebeverine and sulpiride mixtures in pharmaceutical preparation: a comparative
      study.
AB  - Performance of partial least squares regression (PLSR) is enhanced in the
      presented work by three multivariate models, including weighted regression PLSR
      (Weighted-PLSR), genetic algorithm PLSR (GA-PLSR), and wavelet transform PLSR (WT
      PLSR). The proposed models were applied for the stability-indicating analysis of
      mixtures of mebeverine hydrochloride (meb) and sulpiride (sul) in the presence of
      their reported impurities and degradation products. The work introduced in this
      paper aims to compare these different chemometric methods, showing the underlying
      algorithm for each and making a comparison of analysis results. For proper
      analysis, a 6-factor, 5-level experimental design was established resulting in a
      training set of 25 mixtures containing different ratios of the interfering
      species. A test set consisting of 5 mixtures was used to validate the prediction
      ability of the suggested models. Leave one out (LOO) and bootstrap were applied
      to predict number of PLS components. The GA-PLSR proposed method was successfully
      applied for the analysis of raw material (test set 101.03% +/- 1.068, 101.47% +/-
      2.721 for meb and sul, respectively) and pharmaceutical tablets containing meb
      and sul mixtures (10.10% +/- 0.566, 98.16% +/- 1.081 for meb and sul).

PMID- 21898860
TI  - The Drug Information and Monitoring System (DIMS) in the Netherlands:
      implementation, results, and international comparison.
AB  - The Ministry of Health in the Netherlands has made illicit drug testing for drug
      users possible since the 1990s, in order to prevent serious health hazards
      associated with unexpected dangerous substances. This system of illicit drug
      testing is called the Drug Information and Monitoring System (DIMS). In nearly
      two decades, more than 100 000 drug samples have been handed in at DIMS testing
      facilities. This review describes the DIMS methodology and overviews results of
      the three main psychostimulant drug markets that have been monitored, i.e.
      ecstasy, amphetamine (speed), and cocaine. Additionally, monitoring results of
      hallucinogens are also described for the first time. For comparison, alternative
      international monitoring systems are described briefly alongside some of their
      results. Finally, drug monitoring is discussed from the perspectives of policy,
      prevention, and the drug users themselves.

PMID- 21898861
TI  - Effect of self-efficacy and physical activity goal achievement on arthritis pain
      and quality of life in patients with rheumatoid arthritis.
AB  - OBJECTIVE: To examine physical activity and achievement of physical activity
      goals in relation to self-reported pain and quality of life among patients with
      rheumatoid arthritis (RA). METHODS: At baseline, 271 patients with RA were asked
      to specify a physical activity goal, and filled in questionnaires assessing
      physical activity, motivation, and self-efficacy for physical activity, arthritis
      pain, and quality of life. Six months later, patients indicated to what extent
      they had achieved their baseline physical activity goal and completed the same
      set of questionnaires. These data were used to construct multiple mediation
      models that placed physical activity and physical activity goal achievement as
      mediators between self-efficacy and motivation on one hand, and arthritis pain
      and quality of life on the other. RESULTS: A total of 106 patients with RA
      completed both questionnaires. Self-efficacy at baseline predicted subsequent
      level of physical activity and achievement of physical activity goals. Goal
      achievement had a direct effect upon quality of life outcomes. Bootstrapping
      confidence intervals revealed indirect effects of self-efficacy upon arthritis
      pain and quality of life through goal achievement, but not through physical
      activity. CONCLUSION: Higher levels of self-efficacy for physical activity
      increase the likelihood that patients will achieve their physical activity goals.
      Achievement of physical activity goals seems to be related to lower self-reported
      arthritis pain, and higher levels of quality of life. In practice, clinicians can
      foster self-efficacy and goal achievement by assisting patients in setting
      realistic and attainable exercise goals, developing action plans, and by
      providing feedback on goal progress.

PMID- 21898864
TI  - Are posttranslational modifications of beta2-glycoprotein I markers for
      thrombotic risk? Are they triggers of autoimmunity?

PMID- 21898857
TI  - Normal morphogenesis of epithelial tissues and progression of epithelial tumors.
AB  - Epithelial cells organize into various tissue architectures that largely maintain
      their structure throughout the life of an organism. For decades, the
      morphogenesis of epithelial tissues has fascinated scientists at the interface of
      cell, developmental, and molecular biology. Systems biology offers ways to
      combine knowledge from these disciplines by building integrative models that are
      quantitative and predictive. Can such models be useful for gaining a deeper
      understanding of epithelial morphogenesis? Here, we take inventory of some
      recurring themes in epithelial morphogenesis that systems approaches could strive
      to capture. Predictive understanding of morphogenesis at the systems level would
      prove especially valuable for diseases such as cancer, where epithelial tissue
      architecture is profoundly disrupted.

PMID- 21898865
TI  - Endogenous prostaglandin E2 inhibits aberrant overgrowth of rheumatoid synovial
      tissue and the development of osteoclast activity through EP4 receptor.
AB  - OBJECTIVE: We recently developed an ex vivo cellular model of pannus, the
      aberrant overgrowth of human synovial tissue. This study was undertaken to use
      that model to investigate the role of prostaglandin E2 (PGE2) and its receptor
      subtypes in the development of pannus growth and osteoclast activity in
      rheumatoid arthritis (RA). METHODS: Inflammatory cells that infiltrated pannus
      from patients with RA were collected without enzyme digestion and designated
      synovial tissue-derived inflammatory cells. Their single-cell suspensions were
      cultured in medium alone to observe an aberrant overgrowth of inflammatory tissue
      in vitro. Levels of cytokines produced in culture supernatants were measured
      using enzyme-linked immunosorbent assay kits. Osteoclast activity was assessed by
      the development of resorption pits in calcium phosphate-coated slides. RESULTS:
      Primary culture of the synovial tissue-derived inflammatory cells resulted in
      spontaneous reconstruction of inflammatory tissue in vitro within 4 weeks, during
      which tumor necrosis factor alpha, PGE2, macrophage colony-stimulating factor,
      and matrix metalloproteinase 9 were produced in the supernatant. This aberrant
      overgrowth was inhibited by antirheumatic drugs including methotrexate and
      infliximab. On calcium phosphate-coated slides, synovial tissue-derived
      inflammatory cells showed numerous resorption pits. In the presence of inhibitors
      of endogenous prostanoid production such as indomethacin and NS398, exogenous
      PGE1 and EP4-specific agonists significantly inhibited all these activities of
      synovial tissue-derived inflammatory cells in a dose-dependent manner. Addition
      of indomethacin, NS398, or EP4-specific antagonist resulted in the enhancement of
      these cells' activities. EP2-specific agonist had a partial effect, while EP1-
      and EP3-specific agonists had no significant effects. CONCLUSION: These results
      suggest that endogenous PGE2 produced in rheumatoid synovium negatively regulates
      aberrant synovial overgrowth and the development of osteoclast activity via EP4.

PMID- 21898867
TI  - Difficulties in defining antinuclear antibody-positive patients as a separate
      category in the classification of juvenile idiopathic arthritis: comment on the
      article by Ravelli et al.

PMID- 21898868
TI  - New etiopathogenic knowledge, or politics? Comment on the article by Falk et al.

PMID- 21898870
TI  - Robotic surgery offers multiple applications for cancer patients: robots are
      being used to assist with more types of surgery, although there are barriers to
      its widespread adoption.

PMID- 21898872
TI  - Hair loss at 20 associated with prostate cancer risk later in life.

PMID- 21898874
TI  - Ovarian clear cell carcinoma--bad endometriosis or bad endometrium?
AB  - It has become increasingly clear that the four main histological subtypes of
      epithelial ovarian cancer (EOC), high-grade serous, endometrioid, clear cell and
      mucinous, are entities with different epidemiologies, clinical presentations,
      responses to treatment, and ultimate outcomes. In fact, for all intents and
      purposes, they can be considered different diseases, their only common
      denominator being that they frequently involve the ovary and pelvic organs.
      However, clinical practice has not caught up with these insights and the
      treatment of EOC is that of a single disease entity. In part, this is because we
      lack detailed knowledge of the molecular mechanisms driving the pathogenesis of
      each disease, which is vital in order to develop therapeutic approaches against
      common driver events. In the last few years, mutations in ARID1A and PIK3CA have
      been described in a substantial fraction of cases of ovarian clear cell
      carcinoma, yet the paper by Yamamoto et al in this issue of The Journal of
      Pathology reveals that PIK3CA mutations can be detected in precursor
      endometriosis tissues. These and other recent observations underscore the
      importance of investigating whether mutations in the eutopic endometrium actually
      predispose to endometriosis and eventually to malignancy.

PMID- 21898875
TI  - Clonal architecture of human prostatic epithelium in benign and malignant
      conditions.
AB  - The location of stem cells in the epithelium of the prostatic acinus remains
      uncertain, as does the cellular origin of prostatic neoplasia. Here, we apply
      lineage tracing to visualize the clonal progeny of stem cells in benign and
      malignant human prostates and understand the clonal architecture of this
      epithelium. Cells deficient for the mitochondrially-encoded enzyme cytochrome c
      oxidase (CCO) were identified in 27 frozen prostatectomy specimens using dual
      colour enzyme histochemistry and individual CCO-normal and -deficient cell areas
      were laser-capture microdissected. PCR-sequencing of the entire mitochondrial
      genome (mtDNA) of cells from CCO-deficient areas found to share mtDNA mutations
      not present in adjacent CCO-normal cells, thus proving a clonal origin.
      Immunohistochemistry was performed to visualize the three cell lineages normally
      present in the prostatic epithelium. Entire CCO-deficient acini, and part
      deficient acini were found. Deficient patches spanned either basal or luminal
      cells, but sometimes also both epithelial cell types in normal, hyperplastic or
      atrophic epithelium, and prostatic intraepithelial neoplasia (PIN). Patches
      comprising both PIN and invasive cancer were observed. Each cell area within a
      CCO-deficient patch contained an identical mtDNA mutation, defining the patch as
      a clonal unit. CCO-deficient patches in benign epithelium contained basal,
      luminal and endocrine cells, demonstrating multilineage differentiation and
      therefore the presence of a stem cell. Our results demonstrate that the normal,
      atrophic, hypertrophic and atypical (PIN) epithelium of human prostate contains
      stem cell-derived clonal units that actively replenish the epithelium during
      ageing. These deficient areas usually included the basal compartment indicating
      the basal layer as the location of the stem cell. Importantly, single clonal
      units comprised both PIN and invasive cancer, supporting PIN as the pre-invasive
      lesion for prostate cancer.

PMID- 21898876
TI  - In situ lineage tracking of human prostatic epithelial stem cell fate reveals a
      common clonal origin for basal and luminal cells.
AB  - Stem cells accumulate mitochondrial DNA (mtDNA) mutations resulting in an
      observable respiratory chain defect in their progeny, allowing the mapping of
      stem cell fate. There is considerable uncertainty in prostate epithelial biology
      where both basal and luminal stem cells have been described, and in this study
      the clonal relationships within the human prostate epithelial cell layers were
      explored by tracing stem cell fate. Fresh-frozen and formalin-fixed
      histologically-benign prostate samples from 35 patients were studied using
      sequential cytochrome c oxidase (COX)/succinate dehydrogenase (SDH) enzyme
      histochemistry and COX subunit I immunofluorescence to identify areas of
      respiratory chain deficiency; mtDNA mutations were identified by whole
      mitochondrial genome sequencing of laser-captured areas. We demonstrated that
      cells with respiratory chain defects due to somatic mtDNA point mutations were
      present in prostate epithelia and clonally expand in acini. Lineage tracing
      revealed distinct patterning of stem cell fate with mtDNA mutations spreading
      throughout the whole acinus or, more commonly, present as mosaic acinar defects.
      This suggests that individual acini are typically generated from multiple stem
      cells, and the presence of whole COX-deficient acini suggests that a single stem
      cell can also generate an entire branching acinar subunit of the gland.
      Significantly, a common clonal origin for basal, luminal and neuroendocrine cells
      is demonstrated, helping to resolve a key area of debate in human prostate stem
      cell biology.

PMID- 21898878
TI  - Anti-cancer agents for breast cancer treatment during pregnancy.

PMID- 21898879
TI  - Thyroid cysts treated with ethanol ablation can mimic malignancy during
      sonographic follow-up.
AB  - PURPOSE: We aimed to assess long-term ultrasound (US) findings after US-guided
      percutaneous ethanol ablation (EA) in benign thyroid cysts and predominantly
      cystic thyroid nodules. METHODS: Forty patients with thyroid cysts (n = 14) and
      predominantly cystic thyroid nodules (n = 26) underwent long-term US follow-up
      (range, 12-36 months; mean, 18.2 months) after EA. US images of 40 post-EA
      nodules were retrospectively investigated to study the reduction in nodule volume
      and detailed US appearance. RESULTS: On follow-up US, post-EA nodules showed the
      following features: Marked hypoechogenicity (n = 28), spiculated margin (n = 7),
      microcalcifications (n = 6), taller-than-wide shape (n = 2), centrally
      predominant vascularity (n = 3), no vascularity (n = 31), mixed vascularity (n =
      3), and peripheral vascularity (n = 3). Post-EA nodules were diagnosed by US as
      benign (n = 3), probably benign (n = 2), borderline (n = 5), possibly malignant
      (n = 20), and malignant (n = 10). No statistical difference in the incidence of
      malignant US findings was observed between thyroid cysts and predominantly cystic
      thyroid nodules (p > 0.05, Fisher's exact test). CONCLUSIONS: Long-term follow-up
      US after successful EA of benign thyroid cysts and predominantly cystic thyroid
      nodules revealed a high incidence of findings that are usually associated with
      malignancy. Recognizing these consequences of the procedure would help avoid
      unnecessary FNA on post-EA nodules.

PMID- 21898880
TI  - Gracilis myocutaneous flap: evaluation of potential risk factors and long-term
      donor-site morbidity.
AB  - This study reviewed our experience with the gracilis myocutaneous (GMC) flap,
      potential risk factors for flap necrosis, and long-term morbidity at the donor
      site. From 1993 to 2002, 29 GMC flaps were harvested from 27 patients (pedicled n
      = 21 and free n = 8). The overall incidence of flap necrosis was 13.79% (partial
      (n = 2) and total (n = 2) necrosis). Flap necrosis was correlated with body mass
      index >25 (P = 0.022), with smoking (P = 0.04 9) and with radiation therapy at
      the recipient site (P = 0.020). The long-term morbidity at the donor-site was
      low, except for scar appearance (17.24%), thigh contour deformity (58.62%), and
      hypoesthesia (17.24%). Significant age and gender differences were seen for
      ranking of scar ugliness, with females (P = 0.0061) and younger patients (age
      <=55) (P = 0.046) assigned higher values. Significant age differences were seen
      for ranking of thigh contour deformity, with younger patients assigned higher
      values (P = 0.0012). In conclusion, patient overweight, smoking, and previous
      radiation therapy at the recipient site may be the "potential risk factors" for
      flap necrosis. The long-term morbidity at the donor-site was low, which was in
      agreement with previous reported studies. A larger series would be the subject of
      a future study.

PMID- 21898881
TI  - Transverse splitting of the gracilis muscle free flap: Maximal use of a single
      muscle.
AB  - The gracilis muscle, based on the dominant pedicle, has been used extensively for
      free tissue transfer. Recent studies have described the constant anatomy, ease of
      dissection, and low donor-site morbidity of the distal segmental gracilis free
      muscle flap. We present three cases of free distal segmental gracilis muscle
      transfer. In one case, the gracilis muscle was divided transversely into one
      proximally based and one distally based free flap and used for coverage of two
      separate wounds in a patient with bilateral open calcaneal fractures. In two
      cases, the preserved proximal gracilis was used as a reoperative free flap after
      failure of the initial distal segmental gracilis free muscle. With recent
      advances in microsurgery and ever-growing demands for low donor-site morbidity,
      it is important to ensure each free muscle flap harvested is used efficiently.
      Use of the free distal segmental gracilis muscle flap maximally uses one muscle
      while minimizing donor site morbidity and retaining the proximal muscle for
      future uses.

PMID- 21898882
TI  - Preliminary report of preoperative assessment of anterolateral thigh flap
      perforators using real-time virtual sonography system.

PMID- 21898883
TI  - The use of Integra artificial dermis to minimize donor-site morbidity after
      suprafascial or subfascial dissection of the radial forearm flap.

PMID- 21898884
TI  - Discovering the elusive Beauchene: the originator of the disarticulated anatomic
      technique.
AB  - The identity of the Beauchene bearing the name of the widely used disarticulated
      anatomic technique has remained elusive over the years. This article traces the
      skull technique to its originator, Edme Francois Chauvot de Beauchene (ca. 1780
      1830), an anatomist and surgeon. In addition to pioneering this innovative
      anatomic preparation, Edme Francois reported the first known case of an
      intraneural cyst in 1810 and pulmonary air embolism in 1818. The credit has been
      incorrectly attributed to Claude Beauchene, an imaginary anatomist in Paris in
      the 1850s, or to his famous father, Edme Pierre Chauvot de Beauchene (1749-1825),
      a psychologist and physician. The significant accomplishments of Edme Francois
      Chauvot de Beauchene (Beauchene fils or Beauchene son) in medicine have been
      overshadowed by those of his distinguished father and should be fully recognized.

PMID- 21898887
TI  - Unprecedented synthesis of 1,3-dimethylcyclobutadiene in the solid state and
      aqueous solution.
AB  - Cyclobutadiene (CBD), the smallest cyclic hydrocarbon bearing conjugated double
      bonds, has long intrigued chemists because of its chemical characteristics. The
      question of whether the molecule could be prepared at all has been answered, but
      the parent compound and its unperturbed derivatives have eluded crystallographic
      characterization or synthesis "in water". Different approaches have been used to
      generate and to trap cyclobutadiene in a variety of confined environments: a) an
      Ar matrix at cryogenic temperatures, b) a hemicarcerand cage enabling the
      characterization by NMR spectroscopy in solution, and c) a crystalline
      guanidinium-sulfonate-calixarene G(4)C matrix that is stable enough to allow
      photoreactions in the solid state. In the latter case, the 4,6-dimethyl-alpha
      pyrone precursor, Me(2)1, has been immobilized in a guanidinium-sulfonate
      calixarene G(4)C crystalline network through a combination of non-covalent
      interactions. UV irradiation of the crystals transforms the entrapped Me(2)1 into
      a 4,6-dimethyl-Dewar-beta-lactone intermediate, Me(2)2, and rectangular-bent 1,3
      dimethylcyclobutadiene, Me(2)CBD(R), which are sufficiently stable under the
      confined conditions at 175 K to allow a conventional structure determination by X
      ray diffraction. Further irradiation drives the reaction towards
      Me(2)3&Me(2)CBD(S)/CO(2) (63.7 %) and Me(2)CBD(R) (37.3 %) superposed crystalline
      architectures and the amplification of Me(2)CBD(R). The crystallographic models
      are supported by additional FTIR and Raman experiments in the solid state and by
      (1)H NMR spectroscopy and ESI mass spectrometry experiments in aqueous solution.
      Amazingly, the 4,6-dimethyl-Dewar-beta-lactone, Me(2)2, the cyclobutadiene
      carboxyl zwitterion, Me(2)3, and 1,3-dimethylcyclobutadiene, Me(2)CBD, were
      obtained by ultraviolet irradiation of an aqueous solution of G(4)C{Me(2)1}. 1,3
      Dimethylcyclobutadiene is stable in water at room temperature for several weeks
      and even up to 50  degrees C as demonstrated by (1)H NMR spectroscopy.

PMID- 21898890
TI  - A piezochromic luminescent complex: mechanical force induced patterning with a
      high contrast ratio.

PMID- 21898892
TI  - Hospital competition and inpatient services efficiency in Taiwan: a longitudinal
      study.
AB  - There is no consistent evidence of the relationship between market competition
      and hospital efficiency. Some studies indicated that more competition led to a
      faster patient turnover rate, higher hospital costs, and lower hospital
      efficiency. Since the 1980s some studies found market competition could increase
      the efficiency of inpatient services. However, there were few studies testing the
      market competition during a hospital's earlier stages on its efficiency during
      later stages, or the dynamic of efficiency. In this study, we examined the effect
      of early-stage market competition on later-stage hospital efficiency in Taiwan,
      and we determine the efficiency change using longitudinal study design. The data
      for the analysis came from the annual national hospital survey of 1996 and 2001
      provided by the Department of Health. There were 102 teaching hospital be
      analysed. The results show that no evidence supports the proposition that higher
      market competition would improve the efficiency of hospitals in delivering
      inpatient services in Taiwan. Importantly, neither was the inefficiency score nor
      the Malmquist productivity index of inpatient services associated with the level
      of hospital market competition, regardless of the adjustment for hospital
      characteristics. However, the results may be related with the hospital increasing
      beds investment behavior.

PMID- 21898895
TI  - Self-regulation processes and thriving in childhood and adolescence: a view of
      the issues.
AB  - Both organismic and intentional self-regulation processes must be integrated
      across childhood and adolescence for adaptive developmental regulations to exist
      and for the developing person to thrive, both during the first two decades of
      life and through the adult years. To date, such an integrated, life-span approach
      to self-regulation during childhood and adolescence has not been fully
      formulated. The purpose of this monograph is to provide such integration; in this
      introduction, the editors of the monograph explain the purposes of the volume and
      provide a brief overview of the work of the contributing scholars.

PMID- 21898896
TI  - When everything new is well-forgotten old: Vygotsky/Luria insights in the
      development of executive functions.
AB  - The concept of "extra-cortical organization of higher mental functions" proposed
      by Lev Vygotsky and expanded by Alexander Luria extends cultural-historical
      psychology regarding the interplay of natural and cultural factors in the
      development of the human mind. Using the example of self-regulation, the authors
      explore the evolution of this idea from its origins to recent findings on the
      neuropsychological trajectories of the development of executive functions.
      Empirical data derived from the Tools of the Mind project are used to discuss the
      idea of using classroom intervention to study the development of self-regulation
      in early childhood.

PMID- 21898897
TI  - Self-regulation and academic achievement in elementary school children.
AB  - Self-regulation is a key construct in children's healthy and adaptive
      development. In this chapter, the authors situate self-regulation in a
      theoretical context that describes its underlying components that are most
      important for early school success: flexible attention, working memory, and
      inhibitory control. The authors review evidence that supports substantive links
      between these aspects of self-regulation and academic achievement in young
      children. They also discuss methodological challenges in reliably and validly
      assessing these skills (involving measures that are biased, are not applicable
      across broad age ranges, or triangulated) and describe some recent advances in
      measures of self-regulation (involving the NIH Toolbox or the Head-Toes-Knees
      Shoulders assessment) that are reliable, ecologically valid, and predictive of
      children's school achievement.

PMID- 21898898
TI  - Influences of children's and adolescents' action-control processes on school
      achievement, peer relationships, and coping with challenging life events.
AB  - Self-regulation represents a core aspect of human functioning that influences
      positive development across the life span. This chapter focuses on the action
      control model, a key facet of self-regulation during childhood and early
      adolescence. The authors discuss the development of action-control beliefs,
      paying particular attention to their relationship to indices of positive
      development. They then discuss how linking the action-control model with other
      theories of self-regulation can inform our understanding of self-regulation
      across the life span.

PMID- 21898899
TI  - Intentional self-regulation, ecological assets, and thriving in adolescence: a
      developmental systems model.
AB  - The positive youth development (PYD) perspective emphasizes that thriving occurs
      when individual <->context relations involve the alignment of adolescent
      strengths with the resources in their contexts. The authors propose that a key
      component of this relational process is the strength that youth possess in the
      form of self-regulatory processes; these processes optimize opportunities to
      obtain ecological resources that enhance the probability of PYD.  They use the
      selection, optimization, and compensation (SOC) model of intentional self
      regulation to discuss the role of self-regulation in the PYD perspective among
      diverse youth.

PMID- 21898900
TI  - A life-span, relational, public health model of self-regulation: impact on
      individual and community health.
AB  - In this chapter, the authors extend the ideas around the development of self
      regulation and its impact on development by proposing a life-span, relational,
      public health model. They propose that the role of self-regulation should be
      understood across transitions from childhood to adulthood and through an
      individual and community perspective, including the relational process between
      the individual, the community, and contextual factors, such as the social
      determinants of health. These contextual factors may mediate or moderate the
      development of self-regulatory capacity across one's life span, influencing both
      individual and community health. Therefore, to ensure proper self-regulatory
      development, we must address the myriad external factors that undermine the
      development of self-regulation across the life span.

PMID- 21898901
TI  - Adolescents' conscious processes of developing regulation: learning to appraise
      challenges.
AB  - To understand regulation and agency, it important to consider the nature of the
      regulatory challenges that adolescents must deal with. These include emotional,
      motivation, interpersonal, and other obstacles and problems. In this chapter, the
      author discusses the challenges reported by youth working on arts, technology,
      and social justice projects in organized programs and how they learn to address
      them. Adolescents' new higher-order cognitive capacities allow them to better
      understand the irregularities and complexity of real-world challenges. They also
      use these capacities to consciously develop skills to navigate these challenges.

PMID- 21898904
TI  - The impact of altered herbicide residues in transgenic herbicide-resistant crops
      on standard setting for herbicide residues.
AB  - The global area covered with transgenic (genetically modified) crops has rapidly
      increased since their introduction in the mid-1990s. Most of these crops have
      been rendered herbicide resistant, for which it can be envisaged that the
      modification has an impact on the profile and level of herbicide residues within
      these crops. In this article, the four main categories of herbicide resistance,
      including resistance to acetolactate-synthase inhibitors, bromoxynil, glufosinate
      and glyphosate, are reviewed. The topics considered are the molecular mechanism
      underlying the herbicide resistance, the nature and levels of the residues formed
      and their impact on the residue definition and maximum residue limits (MRLs)
      defined by the Codex Alimentarius Commission and national authorities. No general
      conclusions can be drawn concerning the nature and level of residues, which has
      to be done on a case-by-case basis. International residue definitions and MRLs
      are still lacking for some herbicide-crop combinations, and harmonisation is
      therefore recommended.

PMID- 21898905
TI  - Positive association of phencyclidine-responsive genes, PDE4A and PLAT, with
      schizophrenia.
AB  - As schizophrenia-like symptoms are produced by administration of phencyclidine
      (PCP), a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, PCP
      responsive genes could be involved in the pathophysiology of schizophrenia. We
      injected PCP to Wistar rats and isolated five different parts of the brain in 1
      and 4 hr after the injection. We analyzed the gene expression induced by the PCP
      treatment of these tissues using the AGILENT rat cDNA microarray system. We
      observed changes in expression level in 90 genes and 21 ESTs after the treatment.
      Out of the 10 genes showing >2-fold expressional change evaluated by qRT-PCR, we
      selected 7 genes as subjects for the locus-wide association study to identify
      susceptibility genes for schizophrenia in the Japanese population. In haplotype
      analysis, significant associations were detected in combinations of two SNPs of
      BTG2 (P = 1.4 * 10(-6) ), PDE4A (P = 1.4 * 10(-6) ), and PLAT (P = 1 * 10(-3) ),
      after false discovery rate (FDR) correction. Additionally, we not only
      successfully replicated the haplotype associations in PDE4A (P = 6.8 * 10(-12) )
      and PLAT (P = 0.015), but also detected single-point associations of one SNP in
      PDE4A (P = 0.0068) and two SNPs in PLAT (P = 0.0260 and 0.0104) in another larger
      sample set consisting of 2,224 cases and 2,250 controls. These results indicate
      that PDE4A and PLAT may be susceptibility genes for schizophrenia in the Japanese
      population.

PMID- 21898907
TI  - Acrolein.

PMID- 21898908
TI  - Toxicology and risk assessment of acrolein in food.
AB  - Acrolein is an alpha,beta-unsaturated aldehyde formed by thermal treatment of
      animal and vegetable fats, carbohydrates and amino acids. In addition it is
      generated endogenously. As an electrophile, acrolein forms adducts with
      gluthathione and other cellular components and is therefore cytotoxic.
      Mutagenicity was shown in some in vitro tests. Acrolein forms different DNA
      adducts in vivo, but mutagenic and cancerogenous effects have not been
      demonstrated for oral exposure. In subchronic oral studies, local lesions were
      detected in the stomach of rats. Systemic effects have not been reported from
      basic studies. A WHO working group established a tolerable oral acrolein intake
      of 7.5 MUg/kg body weight/day. Acrolein exposure via food cannot be assessed due
      to analytical difficulties and the lack of reliable content measurements. Human
      biomonitoring of an acrolein urinary metabolite allows rough estimates of
      acrolein exposure in the range of a few MUg/kg body weight/day. High exposure
      could be ten times higher after the consumption of certain foods. Although the
      estimation of the dietary acrolein exposure is associated with uncertainties, it
      is concluded that a health risk seems to be unlikely.

PMID- 21898913
TI  - The International Proteomics Tutorial Programme (IPTP): a teaching tool box for
      the proteomics community.
AB  - The most critical functions of the various proteomics organisations are the
      training of young scientists and the dissemination of information to the general
      scientific community. The education committees of the Human Proteome Organisation
      (HUPO) and the European Proteomics Association (EuPA) together with their
      national counterparts are therefore launching the International Proteomics
      Tutorial Programme to meet these needs. The programme is being led by Peter James
      (Sweden), Thierry Rabilloud (France) and Kazuyuki Nakamura (Japan). It involves
      collaboration between the leading proteomics journals: Journal of Proteome
      Research, Journal of Proteomics, Molecular and Cellular Proteomics, and
      Proteomics. The overall level is aimed at Masters/PhD level students who are
      starting out their research and who would benefit from a solid grounding in the
      techniques used in modern protein-based research. The tutorial program will cover
      core techniques and basics as an introduction to scientists new to the field. At
      a later stage the programme may be expanded with a series of more advanced topics
      focussing on the application of proteomics techniques to biological problem
      solving. The entire series of articles and slides will be made freely available
      for teaching use at the Journals and Organisations homepages and at a special
      website, www.proteomicstutorials.org.

PMID- 21898916
TI  - Introduction to Danish (nationwide) registers on health and social issues:
      structure, access, legislation, and archiving.
AB  - Danish registers contain information on many important health and social issues.
      Because all Danish citizens have a unique personal identification number, linkage
      at the individual level between these nationwide registers and other data sources
      is possible and feasible. In this paper we briefly introduce selected Danish
      registers and the data structure and requirements forgetting access to data at
      Statistics Denmark, which is the main provider of register data. We introduce the
      Danish Data Archive and briefly present the Act on Processing of Personal Data,
      which is the legal foundation for analyses of register-based data in Denmark.

PMID- 21898917
TI  - Database on Danish population-based registers for public health and welfare
      research.
AB  - Population-based studies with information from registers can take place in
      Denmark due to linkage between registers at the individual level by means of a
      unique personal identification number (CPR-number), which all persons with
      residence in Denmark have. Registers with information on health can be linked to
      other population registers containing information on, for example, transfer
      payments, education, housing, income, and socioeconomic position. This article
      introduces a database and search engine, which is available for public health and
      welfare researchers as an aid to seek information on the content of important
      Danish registers.

PMID- 21898918
TI  - The Danish Register of Congenital Heart Disease.
AB  - INTRODUCTION: Congenital heart defects (CHD) constitute the largest group of
      congenital defects with a prevalence at birth of 5-11 per 1000 live births, and
      the population of adults with CHD is increasing. However, few population-based
      long-term outcome data exist. CONTENT: The Danish Register of Congenital Heart
      Disease holds data on patients diagnosed with CHD since 1963 and patients below
      25 years of age with other types of heart disease. VALIDITY AND COVERAGE: Overall
      and defect specific validation is ongoing. CONCLUSION: Together with other Danish
      registers, the Danish Register of Congenital Heart Disease provides extensive
      research possibilities.

PMID- 21898919
TI  - Iraq's health system yet to heal from ravages of war.

PMID- 21898920
TI  - Just work.

PMID- 21898921
TI  - Nanomedicine for implants: a review of studies and necessary experimental tools.
AB  - The response of host organisms (including at the protein and cellular level) to
      nanomaterials is different than that observed to conventional materials.
      Nanomaterials are those materials which possess constituents less than 100 nm in
      at least one direction. This review will first introduce the use of nanomaterials
      in a variety of implant applications highlighting their promise towards
      regenerating tissues. Such reviewed studies will emphasize interactions of
      nanomaterials with various proteins and subsequently cells. Moreover, such
      advances in the use of nanomaterials as novel implants have been largely, to
      date, determined by conventional methods. However, the novel structure-property
      relationships unique for nanosized materials reside at the nanoscale. That is,
      the novelty of a nanomaterial can only be fully appreciated by characterizing
      their interactions with biological systems (such as proteins) with nanoscale
      resolution analytical tools. This characterization of nanomaterials at the
      nanoscale is critical to understanding and, hence, further promoting increased
      tissue growth on nanomaterials. For this reason, while more tools are needed for
      this emerging field, this review will also cover currently available surface
      characterization techniques that emphasize nanoscale resolution pertinent for
      characterizing biological interactions with nanomaterials, including attenuated
      total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, X-ray
      photoelectron spectroscopy (XPS), time-of-flight secondary ion mass spectroscopy
      (SIMS), colorimetric biological assays, circular dichroism (CD), and atomic force
      microscopy (AFM). Only through the coordination of nanoscale analytical tools
      with studies that highlight mechanisms of increased tissue growth on
      nanomaterials will we be able to design better implant materials.

PMID- 21898922
TI  - Polling the audience using text messaging--a tool for medical education.

PMID- 21898923
TI  - The time investment in research for clinical educators.

PMID- 21898924
TI  - Revolution in education--new possibilities in education of medical students.

PMID- 21898925
TI  - Reliability and validity of a Chinese version of the Dundee Ready Education
      Environment Measure in the postgraduate context.

PMID- 21898926
TI  - Learning in a new era.

PMID- 21898927
TI  - Incremental cost benefit of an innovation.

PMID- 21898928
TI  - Biological basis of sex differences in psychopharmacology. Preface.

PMID- 21898930
TI  - False normal vitamin B(12) levels caused by  assay error.

PMID- 21898929
TI  - Authors' response.

PMID- 21898931
TI  - The power of partnerships.

PMID- 21898932
TI  - No workforce plan for enrolled nurses.

PMID- 21898933
TI  - [Which project for the nursing profession?].

PMID- 21898934
TI  - [Managing pain in the field of mental health].
AB  - There are no specific tools for assessing pain in mental health. Different pain
      assessment scales can help in understanding the cause, mechanism and intensity.
      However, therapeutic support remains the basic treatment for relieving a
      patient's pain.

PMID- 21898935
TI  - Natural glory in the midst of war: the establishment of Yosemite State Park.

PMID- 21898936
TI  - Toward autonomy in love and work: situating the film "Yo, tambien" within the
      political project of disability studies.
AB  - This essay looks at the representation of disability in the recent Spanish film
      "Yo, tambien" through the lens of disability studies, understood as a political
      project. The film's portrayal of a character who is, like the actor who plays
      him, Europe's first university graduate with Down syndrome, is unique. Moreover,
      "Yo, tambien" provides the opportunity to assess the state of the struggle for
      rights for persons with disabilities both in the film's narrative arc and also in
      the wider Spanish (and global) society. Among other sources, specific articles of
      the United Nations's recent Convention on the Rights of People with Disabilities
      are incorporated into the essay. Both essay and film coincide in emphasizing the
      need to grant disabled populations greater autonomy in the spheres of love and
      work.

PMID- 21898937
TI  - Squatting and urban renewal: the interaction of squatter movements and strategies
      of urban restructuring in Berlin.
AB  - Squatting as a housing strategy and as a tool of urban social movements
      accompanies the development of capitalist cities worldwide. We argue that the
      dynamics of squatter movements are directly connected to strategies of urban
      renewal in that movement conjunctures occur when urban regimes are in crisis. An
      analysis of the history of Berlin squatter movements, their political context and
      their effects on urban policies since the 1970s, clearly shows how massive
      mobilizations at the beginning of the 1980s and in the early 1990s developed in a
      context of transition in regimes of urban renewal. The crisis of Fordist city
      planning at the end of the 1970s provoked a movement of "rehab squatting"
      ('Instandbesetzung'), which contributed to the institutionalization of "cautious
      urban renewal" ('behutsame Stadterneuerung') in an important way. The second
      rupture in Berlin's urban renewal became apparent in 1989 and 1990, when the
      necessity of restoring whole inner-city districts constituted a new, budget
      straining challenge for urban policymaking. Whilst in the 1980s the squatter
      movement became a central condition for and a political factor of the transition
      to "cautious urban renewal," in the 1990s large-scale squatting - mainly in the
      eastern parts of the city - is better understood as an alien element in times of
      neoliberal urban restructuring.

PMID- 21898938
TI  - Ghettos and enclaves in the cross-place realm: mapping socially bounded spaces
      across cities.
AB  - Since the early Chicago School, urban researchers have used residential proximity
      to assess contacts within and between racial and ethnic groups. This approach is
      increasingly limited. Diverse groups use email, social networking sites, instant
      messaging and mobile phones to communicate across urban zones and distant cities.
      These practices enable mutual support among far-flung family members and co
      ethnics as they engage with an array of institutions throughout their day.
      Through interviews and observations that include women and men of diverse
      occupations, races and national origins, the author explores how and why cross
      place enclosures of sociality and resources develop. Rather than framing the
      residential area as the locus of racial/ethnic concentration, the author focuses
      on cross-place concentrations in the technologically mediated workspace. This
      study enhances theorization of the structural negotiations, interpersonal
      pressures and group preferences that produce separate lifeworlds in globalizing
      cities.

PMID- 21898939
TI  - Migration in far west Nepal: intergenerational linkages between internal and
      international migration of rural-to-urban migrants.
AB  - In Nepal, international labor migration to India and overseas, as well as
      internal migration to the rural Nepalese lowlands, is of high socioeconomic
      significance. Scholarly debates about migration in Nepal have gradually shifted
      from an economic to a more holistic perspective, also incorporating social
      dimensions. However, little evidence has been generated about internal migration
      to urban destinations and the potential linkages between international and
      internal migration. This article draws on Bourdieu's "Theory of Practice" and
      sees migration as a social practice. Accordingly, migration practice is regarded
      as a strategy social agents apply to increase or transfer capitals and ultimately
      secure or improve their social position. Evidence for this argument is based on a
      qualitative case study of rural to urban migrants in Far West Nepal conducted in
      July and August 2009. The study at hand addresses linkages between internal and
      international migration practices and provides insight about a social stratum
      that is often neglected in migration research: the middle class and, more
      precisely, government employees. The authors show that social relations are
      crucial for channeling internal migration to a specific destination. Furthermore,
      they unveil how internal migration is connected to the international labor
      migration of former generations. Finally, the authors examine how migration
      strategies adopted over generations create multi-local social networks rooted in
      the family's place of origin.

PMID- 21898940
TI  - Rice farming in Bali: organic production and marketing challenges.
AB  - All is not well with agriculture in Southeast Asia. The productivity gains of the
      Green Revolution have slowed and even reversed and environmental problems and
      shortages of water and land are evident. At the same time changing world markets
      are shifting the dynamics of national agricultural economies. But from the point
      of view of farmers themselves, it is their season-to-season economic survival
      that is at stake. Bali is in some ways typical of other agricultural areas in the
      region, but it is also a special case because of its distinctive economic and
      cultural environment dominated by tourism. In this environment, farmers are
      doubly marginalized. At the same time the island offers them unique market
      opportunities for premium and organic produce. This article examines the ways in
      which these opportunities have been approached and describes their varying
      degrees of success. It focuses especially on one project that has been successful
      in reducing production costs by conversion to organic production, but less so in
      marketing its produce. It argues finally for the need for integrated studies of
      the entire rice production/marketing complex, especially from the bottom-up point
      of view of farmers.

PMID- 21898941
TI  - Famines past, famine's future.
AB  - Famine, like poverty, has always been with us. No region and no century has been
      immune. Its scars - economic, psychological and political - can long outlast its
      immediate impact on mortality and health. Famines are a hallmark of economic
      backwardness, and were thus more likely to occur in the pre-industrialized past.
      Yet the twentieth century suffered some of the most devastating ever recorded.
      That century also saw shifts in both the causes and symptoms of famine. This new
      century's famines have been "small" by historical standards, and the threat of
      major ones seemingly confined to ever-smaller pockets of the globe. Are these
      shifts a sign of hope for the future?

PMID- 21898942
TI  - Violence and compassion: a bioethical insight into their cognitive bases and
      social manifestations.
AB  - This article considers the social problem of violence and the alternative of
      resolution through cooperation and compassion from the perspective of cognitive
      neuroscience. Violence is a social problem, the manifestations of which have a
      biological basis reflected in the development of aggression and the neural
      mechanisms that regulate it. Cooperation and compassion are two forms of
      behaviour with similar developmental, cognitive and cerebral regulatory bases to
      the mechanisms activated in violence, even though they result in radically
      different forms of behaviour. The article examines violence and compassion as two
      mechanisms that lead to moral action that depends on whether sociocultural
      contexts are adverse or favourable to human well-being. It concludes that the
      neuro-cognitive system is a flexible and adaptable mechanism that regulates
      behaviour directly, according to the sociocultural context in which individuals
      live. Against that background, the UNESCO Declarations on the culture of peace
      refer to concepts relating to cognition or the human mind. Cognitive neuroscience
      therefore provides tools for creating and changing mental concepts that could
      eventually enable human beings to live together in peace.

PMID- 21898943
TI  - The psychobiology of aggression and violence: bioethical implications.
AB  - Bioethics is concerned with the moral aspects of biology and medicine. The
      bioethical relevance of aggression and violence is clear, as very different moral
      and legal responsibilities may apply depending on whether aggression and violence
      are forms of behaviour that are innate or acquired, deliberate or automatic or
      not, or understandable and justifiable based on causes. Biological research and
      natural science theories are a basic ingredient for reflections, arguments and
      decisions on such matters. This study presents the problem of the causes of
      aggressive behaviour, the evolutionary understanding and definition of aggressive
      behaviour, the biological basis for this behaviour and the link between emotions
      and aggression. A growing body of evidence suggests that innate factors of
      behaviour (be they genetic or neurobiological) do not by themselves define
      behaviour and nor do acquired factors such as learning, cultural norms or
      worldviews. Both types of factor interact from the outset to shape a development
      process that mutually interacts to define beliefs or behaviour.

PMID- 21898944
TI  - Young people, multiculturalism, and educational interventions for the development
      of empathy.
AB  - As is maintained in the Seville Statement on Violence, the role of education in
      shaping human relations is fundamental. In order to develop effective educational
      interventions aiming to foster empathic relations, some important prerequisites
      need to be satisfied. One of these prerequisites, which is based on a
      constructivist model, is constituted by the identification and analysis of the
      pre-existing concepts and attitudes of those to whom interventions are directed,
      regarding the specific issues involved in the specific educational process. More
      effective positive changes can be obtained this way as they are generated from
      within the individuals themselves. Using this perspective, a study was conducted
      in Italian schools on the attitudes of young people between 9-18 years of age
      towards multiculturalism in contemporary society. The participants (N=350, 176
      girls and 174 boys) were invited to write down anonymously their thoughts about
      multiculturalism. Their essays were quantitatively and qualitatively analysed.
      The aim was to obtain a deep understanding not only of the explicit but also of
      the implicit meaning of the texts and consequently also of the motivations
      underlying the participants' attitudes. Some of the results of this study are
      discussed and suggestions are made for the development of educational
      interventions aiming to foster young people's empathic attitudes.

PMID- 21898945
TI  - The usefulness of distinguishing types of aggression by function.
AB  - Far from being a universally defined notion, aggression is a changing and
      multifaceted phenomenon encompassing various concepts. There is no consensus as
      to how different types of aggression should be classified: multiple ways of doing
      so using a variety of criteria exist in the scientific literature. Some
      scientists categorise aggressive acts according to how they are expressed, while
      others prefer to look at motive, function, purpose and objective. Despite the
      claim of some authors that distinguishing between different types of aggressive
      acts is not always productive, categorising these according to different purposes
      and objectives can be very useful, both for developing theory and because such an
      approach serves forensic practice as well as preventive and therapeutic
      interventions, as these focus on the propensities and personality of the
      individual. Furthermore, given that the main functional classifications analysed
      show a common tendency to dichotomise, it would seem appropriate for their
      terminology and some of their measurement instruments to be standardised.

PMID- 21898946
TI  - Between affiliation and autonomy: navigating pathways of women's empowerment and
      gender justice in rural Bangladesh.
AB  - Inasmuch as women's subordinate status is a product of the patriarchal structures
      of constraint that prevail in specific contexts, pathways of women's empowerment
      are likely to be "path dependent." They will be shaped by women's struggles to
      act on the constraints that prevail in their societies, as much by what they seek
      to defend as by what they seek to change. The universal value that many feminists
      claim for individual autonomy may not therefore have the same purchase in all
      contexts. This article examines processes of empowerment as they play out in the
      lives of women associated with social mobilization organizations in the specific
      context of rural Bangladesh. It draws on their narratives to explore the
      collective strategies through which these organizations sought to empower the
      women and how they in turn drew on their newly established "communities of
      practice" to navigate their own pathways to wider social change. It concludes
      that while the value attached to social affiliations by the women in the study is
      clearly a product of the societies in which they have grown up, it may be no more
      context-specific than the apparently universal value attached to individual
      autonomy by many feminists.

PMID- 21898947
TI  - Food, feed, fuel: transforming the competition for grains.
AB  - Critical changes are underway in the domain of grain utilization. With the large
      scale diversion of corn for the manufacture of ethanol, the bulk of it in the
      USA, there has been a transformation of the food-feed competition that emerged in
      the twentieth century and characterized the world's grain consumption after World
      War II. Concerns have already been expressed in several quarters regarding the
      role of corn-based ethanol in the recent food price spike and the global food
      crisis. In this context, this article attempts to outline the theoretical tenets
      of a food-feed-fuel competition in the domain of grain consumption. The study
      focuses on developments in the US economy from 1980 onwards, when the earliest
      initiatives on bio-fuel promotion were undertaken. The transformation of the
      erstwhile food-feed competition with the introduction of fuel as a further use
      for grains has caused a new dynamics of adjustments between the different uses of
      grains. This tilts the distribution of cereal consumption drastically against the
      low-income classes and poses tougher challenges in the fight against global
      hunger.

PMID- 21898948
TI  - [Bioethical problems in neurosciences].

PMID- 21898949
TI  - [The experience of non-medication treatment of patients with Parkinson's disease
      in "School of Health"].

PMID- 21898950
TI  - [A case of successful psychotherapy of schizoid personality disorder with
      hypochondria using the method of creative self-expression].

PMID- 21898951
TI  - [Pharmacoeconomic aspects of migraine].

PMID- 21898952
TI  - [Diagnosis of primary of symptomatic forms of chronic daily headache].

PMID- 21898953
TI  - [The use of tanakan in the treatment of vestibular-ataxic syndrome in patients
      with chronic cerebral ischemia].

PMID- 21898954
TI  - [Rehabilitation of newborns with perinatal lesions of the central nervous system
      using transcranial magnetic therapy].

PMID- 21898955
TI  - [Some clinical features of bacterial infections with a syndrome of purulent
      meningitis].

PMID- 21898956
TI  - [Peculiarities of the formation and correlations between EEG changes and clinical
      symptoms in children].

PMID- 21898957
TI  - [Flupirtin (katadolon): a nonstandard action on pain transmission].

PMID- 21898958
TI  - [Personality features in adolescents with internet addiction].

PMID- 21898959
TI  - Normal maturation involves systematic changes in binocular visual connections in
      Xenopus laevis.
AB  - Systematic changes in neuronal connections have been observed during the
      development of many vertebrate neuronal systems. These changes have usually
      involved a refinement from an initial exuberance of connections or a response to
      some experimental perturbation. Here we report on a system of neuronal
      connections, which, during a protracted developmental period, undergo ordered
      changes in response to normally occurring changes in functional requirements. In
      the frog Xenopus laevis, interocular alignment changes markedly during late
      larval and post-metamorphic life, producing a progressive enlargement of the
      binocular portion of the visual field. An intertectal system links the two mid
      brain optic tecta and is concerned with the neural representation of binocular
      visual space. In the adult animal, connections in this system link corresponding
      points (points receiving information from one locus of binocular visual space) on
      the two tecta. Changes in eye position with development, however, change the set
      of corresponding points. Therefore, if the intertectal connections link
      corresponding tectal points throughout development, they must undergo an ordered
      change with time. We present electrophysiological evidence that the intertectal
      connections do, indeed, undergo such changes in response to changes in eye
      alignment, and that the changes are major.

PMID- 21898960
TI  - Measurement of the intracellular free calcium concentration in salamander rods.
AB  - Measurement of the free calcium concentration within a photo-receptor outer
      segment has been considered an important aim since the proposal by Hagins and
      Yoshikami that the primary event in phototransduction is a release of Ca (2+)
      inside the cell. More recent evidence has cast doubt on the calcium hypothesis,
      and the observations of Yau and Nakatani and Matthews et al. suggest that the
      internal Ca (2+) concentration ([Ca (2+)]i), may decrease after a flash of light.
      In the present study we have measured [Ca (2+)]i directly by using a new method
      for incorporating the Ca-sensitive photoprotein aequorin into an isolated rod. We
      report that the light response is accompanied by a decrease in [Ca (2+)]i, caused
      by the closure of light-sensitive channels which are the main route for Ca (2+)
      entry into the outer segment. Of the Ca (2+) entering through light-sensitive
      channels, about 95% is sequestered by a rapid and reversible buffering mechanism.
      Calcium is removed from the cell by an electrogenic pump in which 3 Na (+) ions
      are exchanged for each Ca (2+); the pump is highly active and the free Ca (2+) in
      the cell declines with a time constant of ~0.5 s after a flash of light.

PMID- 21898961
TI  - New technologies applied to family history: a particular case of southern Europe
      in the eighteenth century.
AB  - In this article, the author explains how the support of new technologies has
      helped historians to develop their research over the last few decades. The
      author, therefore, summarizes the application of both database and genealogical
      programs for the southern Europe family studies as a methodological tool. First,
      the author will establish the importance of the creation of databases using the
      File Maker program, after which they will explain the value of using genealogical
      programs such as Genopro and Heredis. The main aim of this article is to give
      detail about the use of these new technologies as applied to a particular study
      of southern Europe, specifically the Crown of Castile, during the late modern
      period. The use of these computer programs has helped to develop the field of
      social sciences and family history, in particular, social history, during the
      last decade.

PMID- 21898962
TI  - The effect of ethnicity and economy upon intergenerational coresidence: northern
      Norway during the last part of the nineteenth century.
AB  - During the last part of the nineteenth century, Finnmark province and the
      northern part of Troms experienced a decline in intergenerational coresidence.
      This article discusses what impact ethnic affiliation and economic activity had
      on the living arrangements of the elderly, and what contributed to the change.
      Logistic regression shows that ethnicity played a role but its effect disappears
      after controlling for economic activity. Intergenerational coresidence was
      positively associated with being a married Sami male with an occupation in
      farming or combined fishing and farming. As such a person grew older, he was
      increasingly likely to live separately from an own adult child. This pattern
      changed toward the end of nineteenth century. By the close of the century, ethnic
      differences had disappeared, and headship position, irrespective of marital
      status, was strongly related to coresidence.

PMID- 21898963
TI  - The Fifth Adam Smith Award in Mental Health Policy and Economics Research.
      Editorial.

PMID- 21898964
TI  - The role of the Toronto Girls' Home, 1863-1910.
AB  - It has been suggested that the role of Ontario children's homes, who had for half
      a century been helping disadvantaged children, changed significantly and
      immediately under the 'Children's Protection Act of 1893'. However, the records
      of the girls admitted to Toronto Girls' Home from 1863 to 1910 suggest that this
      was not the case, for this home at least. For most of their history, their core
      clientele was the children of poor respectable parents dealing with a crisis or
      who could not both work and care for their children. Thus, although prior to 1893
      they did also care for a significant number of neglected children, and after 1893
      fewer such children were admitted, the Home continued for more than 20 years to
      help families as they always had, providing a form of family support for which
      the child protection system was not designed.

PMID- 21898965
TI  - Social mobility and reproduction among nineteenth-century Colorado silver
      prospectors.
AB  - Popular cultural convention holds that, for those with enough gumption, the
      American frontier was a land of unparalleled opportunity. However, careful
      research throws doubt on the universality of this convention. Thus, the authors
      explore factors that increase or decrease opportunities for upward mobility in
      frontier towns. The authors' longitudinal study of late nineteenth century silver
      prospectors in Gothic, Colorado, demonstrates that while enthusiastic prospecting
      in Gothic did not lead to upward social mobility, it did provide enhanced
      reproductive opportunities.

PMID- 21898966
TI  - More than a photo: Germans from Russia remember their familial relationships.
AB  - Most narrators of the Dakota Memories Oral History Project (DMOHP), the children
      and grandchildren of ethnic German immigrants from Russia, reminisce a great deal
      about their family relationships -- grandparent-grandchild relationships, parent
      child relationships, and sibling-sibling relationships. They share memories of
      their grandmothers baking them delicious dough dishes, of their fathers making
      them labor endlessly in the fields, and of their siblings coaxing them into
      mischief. Through these relationships, Germans from Russia not only learned about
      their ethnic group's identity, but they also reshaped it into a new identity,
      blending their past with their present. Within the context of family
      relationships, these German Russian descendants forged a new identity rooted in
      their ethnic heritage and history, but serviceable to new, American-born
      generations.

PMID- 21898967
TI  - Casualties.
AB  - Privation and disease have mainly killed soldiers until very recently. Now that
      enemy action predominates, faster and better control of bleeding and infection
      before and during evacuation spares ever more lives today. This essay focuses on
      psychological war wounds, placing them in the context of military casualties. The
      surgeon's concepts of 'primary' wounds in war, and of would 'complications' and
      'contamination', serve as models for psychological and moral injury in war.
      'Psychological injury' is explained and preferred to 'Post-Traumatic Stress
      Disorder', being less stigmatizing and more faithful to the phenomenon. Primary
      psychological injury equates to the direct damage done by a bullet; the
      complications - for example, alcohol abuse - equate to hemorrhage and infection.
      Two current senses of 'moral injury' equate to wound contamination. As with
      physical wounds, it is the complications and contamination of mental wounds that
      most often kill service members or veterans, or blight their lives.

PMID- 21898968
TI  - [Clinical concepts associated with lithium underutilization in the treatment of
      bipolar disorder].
AB  - OBJECTIVES: Bipolar Disorders are among the ten leading causes of morbity and
      lithium is considered first-line treatment and the most cost-effective.
      Nevertheless, its use takes a back seat to other treatment options less
      effective, safe and more expensive; and the reasons for this remains unclear. The
      present study investigates clinical concepts related to its underutilization.
      METHOD: An anonymous questionnaire concerning different aspects of lithium
      clinical use (compared efficacy, adverse effects, practical aspects regarding its
      use, use in special populations) was administered during the XXV Congress of the
      Argentinean Psychiatrist Association. RESULTS: 164 questionnaires were analyzed.
      Less than one-third of the sample referred lithium as their most frequent
      treatment option, although almost 60% qualified it as effective. Almost two
      thirds considered its utilization as more complex and ill-ascribed adverse
      effects to it. One third referred not to use it in youth and senior populations.
      CONCLUSIONS: Contrary to current recommendations, lithium is under utilized. This
      is the first report on the possible causes leading to such phenomena, which can
      be related to ill concepts regarding its safety, clinical use and adverse
      effects; although not to its effectiveness.

PMID- 21898969
TI  - Imaging of protease functions--current guide to spotting cysteine cathepsins in
      classical and novel scenes of action in mammalian epithelial cells and tissues.
AB  - The human genome encodes some hundreds of proteases. Many of these are well
      studied and understood with respect to their biochemistry, molecular mechanisms
      of proteolytic cleavage, expression patterns, molecular structure, substrate
      preferences and regulatory mechanisms, including their endogenous inhibitors.
      Moreover, precise determination of protease localisation within subcellular
      compartments, peri- and extracellular spaces has been extremely useful in
      elucidating biological functions of peptidases. This can be achieved by refined
      methodology as will be demonstrated herein for the cysteine cathepsins. Besides
      localisation, it is now feasible to study in situ enzymatic activity at the
      various levels of subcellular compartments, cells, tissues, and even whole
      organisms including mouse.

PMID- 21898970
TI  - Localization of the autonomic, somatic and sensory neurons innervating the
      cranial tibial muscle of the pig.
AB  - The location of sympathetic, somatic and sensory neurons projecting to the
      cranial tibial muscle of the pig hindlimb was studied with the neuronal non
      transynaptic tracer Fast Blue. Additionally, the number and the size of these
      neurons were determinated. The Fast blue, randomly applied to the cranial tibial
      muscle belly of 3 pigs, labelled sympathetic neurons in the ipsilateral L5-S3 and
      contralateral S1 sympathetic trunk ganglia and in the prevertebral caudal
      mesenteric ganglia of both sides. The somatic motoneurons were identified in the
      ipsilateral ventral horn of the S1 segment of spinal cord, while the sensory
      neurons were located in the ipsilateral L7-S1 spinal ganglia. The diameter of the
      multipolar sympathetic neurons oscillated between 26 and 46 microm in the
      sympathetic trunk ganglia and between 18 and 42 microm in the caudal mesenteric
      ganglia. The size of the multipolar spinal motoneurons oscillated between 33 and
      102 microm. The size of the pseudounipolar sensory neurons oscillated between 23
      and 67 microm. In all ganglia, the labelled neurons were localized at random and
      did not show a somatotopic distribution. Our results document a conspicuous
      autonomic innervation projecting to the "classic" skeletal cranial tibial muscle.
      Probably this innervation is destined to the muscle vessels.

PMID- 21898971
TI  - Osteonic organization of limb bones in mammals, including humans, and birds: a
      preliminary study.
AB  - As it is well known, bone tissue is characterized by a calcified extracellular
      matrix which makes this tissue suitable to support the body and protect the inner
      organs. Lamellar bone tissue is organized in lamellae, 3-7 microm in thickness,
      and arranged concentrically around vascular channels: the basic structure in this
      type of organization is called Haversian system or osteon and the diameter of
      osteons depends on the number of lamellae. Shape and regional density of osteons
      are related to the bone segment and the specific functional requirements to meet.
      Aim of this study is to correlate the compact bone tissue microstructure in
      various classes of mammals, including humans, and birds in order to find an
      adequate identification key. The results of our study show that in bone tissue
      samples from various classes of mammals, including humans, and birds the osteonic
      structure shows peculiar features, often depending on the rate of bone
      remodelling, different in different animal species. We conclude that a careful
      microscopic analysis of bone tissue and the characterization of distinctive
      osteonic features could give a major contribution to forensic medicine to obtain
      a more reliable recognition of bone findings.

PMID- 21898972
TI  - Some aspects of the craniofacial indices and macro neurometrics of the Nigerian
      local pig (Sus scrofa).
AB  - This study is about the craniofacial indices and neuromorphometrics of the
      Nigerian local pig and has been performed on twelve males and fourteen females of
      ages one and a half to two years. The average values obtained for the tongue
      length, tongue weight, rasp length, left pinna length, right pinna length, left
      pinna width, right pinna width, height of left external nares, height of right
      external nares and the rima oris length were 17 +/- 1.3 cm, 90 +/- 16 g, 4.6 +/-
      0.58 cm, 13 +/- 1.3 cm, 13 +/- 1.3 cm, 8.7 +/- 1.5 cm, 8.7 +/- 1.4 cm, 0.98 +/-
      0.12 cm, 0.96 +/- 0.13 cm and 19.51 +/- 2.89 cm respectively, while the mean
      brain weight, mean brain length, cerebrum and cerebellum lengths, brain and
      cerebellar heights were 84 +/- 12 g, 6.9 +/- 1.5 cm, 4.9 +/- 1.7 cm, 2.2 +/- 1.0
      cm, 5.2 +/- 0.88 cm and 3.0 +/- 1.1 cm respectively. There was a negative
      correlation between the weight of the animal and the height of the cerebellum,
      the length of cerebrum and length of the cerebellum and between the weight of the
      head and height of the cerebellum. A positive correlation was however observed
      between the length of brain and the weight of brain, and between the length of
      the cerebrum and weight of brain. The cerebral length was statistically longer (P
      < 0.01) in the males than the females. The data obtained from this study will
      provide added information in the field of comparative anatomy and porcine
      neuroanatomy research.

PMID- 21898973
TI  - Accessory muscles around the superior radioulnar joint: a morphological study.
AB  - During anatomical dissections on 36 human elbow joints, we observed the presence
      of three muscles around the superior radioulnar joint usually neglected by the
      classical anatomical literature, the lateral tensor muscle of the annular
      ligament (with an incidence of 16.6%), the medial tensor muscle of the annular
      ligament (11.1%) and the accessory supinator muscle (16.6%). We could not
      establish any association between the subject handedness and the sidedness of
      these aberrant muscles, neither we found a predominance in sidedness or in
      gender. Furthermore, we did not notice any significant predominance related to
      the occupation and specifically to heavy labor occupations. On the contrary we
      found these muscles to be more common in non-laborers, which supports the
      assumption that these variants constitute rather genetic than epigenetic traits.
      The knowledge of such anatomical variants facilitate the surgeon operating in the
      elbow region to better interpret supernumerary muscular bundles in the operative
      field.

PMID- 21898974
TI  - The eminent Italian scholar Pietro d'Abano (1250-1315) and his contribution in
      anatomy.
AB  - Pietro d'Abano is recognized as a leading figure in the early history of European
      medical faculties. Translator and scholar, he translated and commented in Latin
      the doctrines of Greek and Arab physicians and philosophers having an ambitious
      attempt, to reconcile the opposing views of Arab medicine and Greek natural
      philosophy. Moreover he was one of the first to claim, three centuries before
      Harvey, that the heart is the source of blood vessels.

PMID- 21898975
TI  - A rare case report of subscapular artery.
AB  - Axillary artery is one of the most important arteries of the upper limb, which is
      a continua- tion of the subclavian artery. It begins at the lateral border of the
      first rib and ends at the inferior border of the teres major where it becomes the
      brachial artery. Axillary artery has six important branches included: 1) Superior
      thoracic artery 2) Thoracoacromial artery 3) Lateral thoracic artery 4)
      Subscapular artery 5) Posterior circumflex humeral artery 6) Anterior circumflex
      humeral artery. Subscapular artery arises from the third part of axillary artery
      normally and then divides into cir- cumflex scapular artery that extremely enters
      the triangular space. The other branch of subscapular artery, the thoracodorsal
      artery, accompanies thracodorsal nerve to lateral border of scapula and supplies
      and innervates that region. In this case the subscapular artery was absent in
      both sides and instead of that the circumflex scapular artery was directly
      derived from axillary artery and the thoracodorsal artery is separated from
      circumflex scapular artery as a thin and short branch, too. It seemed that the
      lateral thoracic artery, which was thicker than its normal condition, supplied
      the muscles of the lateral part of scapula and the thoracodorsal muscle. Other
      branches of the axillary artery demonstrated without any abnormally. Since
      axillary artery has the highest rate of rapture and damage coming after the
      popliteal artery, knowing the variations is important and essential for surgeons,
      radiologist and anatomist.

PMID- 21898977
TI  - [Christian Keferstein - an amateur geologist in central Germany around 1800 and
      his journal "Teutschland shown geognostically - geologically"].
AB  - Christian Keferstein (1784-1866) was a self-educated geologist in early 19th
      century Germany. His pre-scientific period may be regarded as an example of how
      research in nature was conducted not only by academics but also by so called
      "Dilettanten" (amateurs). Keferstein's journal Teutschland, geognostisch
      geologisch dargestellt was published for over ten years beginning from 1821 and
      was intended to provide a forum for geological studies in Germany. The fact that
      Johann Wolfgang von Goethe colored a geological map as an insert for the 1st
      edition of the journal shows how dilettantism was part of professional research,
      even though experts did hardly refer to it. This article is to show how this kind
      of common research was done during the early stages of geology--when the
      discipline was still open to amateurs--and how results could be published.
      Therefore the profile of Keferstein's journal reflects not only the specifics of
      amateurs observations but also a lack of experts that could satisfy the need for
      standardized observations, especially for the production of detailed maps.

PMID- 21898976
TI  - [Skyblue - the cyanometer of Horace-Benedict de Saussure (1740 - 1799)].
AB  - The cyanometer is a simply constructed measuring instrument that enables a
      determination of skyblue. It consists of a color-scale that is arranged
      circularly going in equal steps from white to blue (Prussian blue) and finally
      into black. According to its inventor--Horace-Benedict de Saussure--the azure is
      determined by the amount of so called opaque vapors in the atmosphere associated
      with meteorological phenomena. As outlined by De Saussure, the blackness of the
      universe seen through an illuminated and blurred medium results in azure. Thereby
      his instrument offers a relative scale that is consistent with color theories of
      his time like those of Johann Wolfgang von Goethe. The description allows the
      construction of the scale without the employment of standardized color-prints.
      Instead he provides a clear report of the necessary procedures to produce such a
      scale. The accuracy of this description is tested and discussed employing the
      methods of experimental history of science. The reception of the cyanometer in
      the time about 1800 and its implications on color theories is discussed.

PMID- 21898978
TI  - [Mathematics - astronomy - astrology special library].
AB  - About 1560 Elector August of Saxony created an unusual library--one distinguished
      within its period by both its specialization and location. Situated within the
      Kunstkammer this library was mostly dedicated to the mathematical sciences and
      related disciplines. It contained works by the most important authors on
      mathematics, astronomy, and astrology from the classical, medieval, and early
      modern periods. This essay traces the formation and composition of August's
      library, and examines its function: What kind of relationship existed between the
      library and the Kunstkammer? In what way did the library mirror the interests of
      the Elector, and to what extend does it permit inferences regarding the Elector's
      knowledge of mathematics? From the analysis August emerges not as a specialist
      with a deep understanding of mathematics, but as a particular aficionado of
      mathematical applications. As a practitioner and general follower of the
      mathematical arts he took part in a far-reaching intellectual network the center
      of which lay in the University of Wittenberg. Here, Melanchthon had effectively
      strengthened the importance of the mathematical disciplines within the university
      curriculum. He regarded mathematics as the foremost science, arguing that before
      all other disciplines its method enabled man to recognize the harmonic order of
      the world, and to discern divine providence. Thus, mathematics offered consoling
      stability and support in an often seemingly chaotic world torn by religious
      controversies. This kind of esteem for the mathematical sciences did not
      presuppose expert knowledge. Hence, the fact that August does not appear to have
      read the mathematical books he collected does not come as a contradiction. On the
      contrary, for August it sufficed to recognize the potential of the mathematical
      sciences, which he brought into life through the creation of a specialized
      library that developed a rhetoric of its own. The collection of his Kunstkammer
      library spoke of a harmonically ordered world while at the same time
      memorializing August as a lover of mathematics and an important figure within the
      group of mathematical experts and enthusiasts.

PMID- 21898979
TI  - [Illustrations of of alchemy vessels in a manuscript of Pseudo-Geber].
AB  - Manuscript ric. 933 "Geber de investigatione perfectionis magisterii", kept in
      the Libreria Riccardiana in Florence, is a 13th century Latin version of the
      "Book of the Secret of the Secrets" ("kitab sirr al-asrar") by the Arabian
      alchemist al-Razi (865-925). The manuscript shows on page 25r a series of
      drawings of alchemistic vessels and apparatus which do not figure in the Arabian
      original but which are of particular interest as they date from as early as the
      13th century and are numbered amongst the earliest drawings of this kind which we
      possess. The publication of the manuscript by Julius Ruska in 1935 shows only
      copied drawings with his interpretations of the legends. There was considerable
      interest in the publication of the original page 25r and in the course of further
      study it became clear that these interpretations had to be revised. These new
      interpretations presented in detail in this paper are justified and put into an
      alchemistic context. In some cases they give a new understanding and differ
      considerably from Ruska's versions.

PMID- 21898980
TI  - [Production of glass in early middle ages].
AB  - For the production of glass three ingredients are necessary: sand, a flux to
      reduce the melting-temperature and calcium to reduce the danger of glass
      corrosion. The first objects of glass were made with calcium-rich ashes of
      halophytic plants, until, in the first millennium BC, the glassmakers began to
      use natron as a flux adding calcium deliberately or choosing a calcium-rich sand.
      Natron, a mineral applied to fertilize or to preserve, as a spice, a detergent or
      part of medical and cosmetic articles, was exploited in the regions south and
      east of the Mediterranean, so the Central European glassmakers had to import
      natron or the prefabricated raw glass for their work. Beginning in the 8th
      century AD in Central Europe the flux changed again: The glassmakers increasingly
      used ashes from wood growing in their native regions so becoming independent of
      the necessity to import the raw materials. There are various reasons for this
      change: First, the Mediterranean was no longer the trade area it had been at the
      time of the antique Roman Empire due to the activities of the Byzantine navy.
      Then, the climatic change in the 8th century and political upheavals during the
      9th century in Egypt--being the main supplier of natron--caused a decrease in
      exploitation and trade with this good. Finally, the Egyptian state established a
      monopoly on the natron production, causing a permanent price increase.
      Nevertheless, during the Early Middle Ages natron was imported into Europe,
      although not necessarily for glass production. The article shows that glassmakers
      of Central Europe were able to produce glass since the end of the Western Roman
      Empire on the basis of the transfer of raw materials and know-how from the East.
      From the 8th century onwards they emancipated themselves from the dependency on
      imports by discovering and using native materials for glass production.

PMID- 21898981
TI  - Ryan's hope--or folly?

PMID- 21898982
TI  - Nonprofit health care market concentration and the public interest.

PMID- 21898983
TI  - Is fragmented financing bad for your health?
AB  - Americans finance health care through a variety of private insurance plans and
      public programs. This organizational fragmentation could threaten continuity of
      care and adversely affect outcomes. Using a large sample of veterans who were
      eligible for mixtures of Veterans Health Administration- and Medicare-financed
      care, we estimate a system of equations to account for simultaneity in the
      determination of financing configuration and the probability of hospitalization
      for an ambulatory care sensitive condition. We find that a change of one standard
      deviation in financing fragmentation increases the risk of an adverse outcome by
      one-fifth.

PMID- 21898984
TI  - Why are low-income teens more likely to lack health insurance than their younger
      peers?
AB  - Low-income teenagers are more likely to lack health insurance than younger
      children. Using data from the 2006, 2007, and 2008 rounds of the National Health
      Interview Survey, we examine whether differences between teens and younger
      children in socioeconomic factors, public health insurance eligibility, and
      observable family characteristics explain this apparent age-related coverage gap.
      Somewhat surprisingly, they do not. We find a highly robust age-coverage gradient
      among poor and near-poor children. Our results suggest the need to examine teen
      specific insurance enrollment dynamics, particularly in families with no younger
      siblings, to optimize the effect of the newly enacted Patient Protection and
      Affordable Care Act on teens' insurance coverage.

PMID- 21898985
TI  - Geographic market definition: the case of Medicare-reimbursed skilled nursing
      facility care.
AB  - Correct geographic market definition is important to study the impact of
      competition. In the nursing home industry, most studies use geopolitical
      boundaries to define markets. This paper uses the Minimum Data Set to generate an
      alternative market definition based on patient flows for Medicare skilled nursing
      facilities. These distances are regressed against a range of nursing home and
      area characteristics to determine what influences market size. We compared
      Herfindahl-Hirschman Indices based on county and resident-flow measures of
      geographic market definition. Evidence from this comparison suggests that using
      the county for the market definition is not appropriate across all states.

PMID- 21898986
TI  - Individual insurance and access to care.
AB  - Starting in 2014, more Americans will have private, nonemployment-related
      insurance ("individual insurance"). Using the nationally representative Medical
      Expenditure Panel Survey for 2002 through 2007, this paper compares access to
      care between nonelderly adults with individual insurance and those with
      employment-related insurance. Adults with individual and employment-related
      insurance report similar, often good, access to care. The study employs bivariate
      probit models to account for omitted variables correlated with access and type of
      insurance, and controls for differences in health status, attitudes, and
      socioeconomic characteristics. Results show that individual insurance may reduce
      access in some dimensions, but all effects are imprecisely estimated, so that
      none is statistically significant.

PMID- 21898987
TI  - [Correlation between hypertension and erectile dysfunction].
AB  - The relationship between erectile dysfunction (ED) and hypertension is a focus in
      andrological research. ED and hypertension share some pathophysiologic pathways,
      such as oxidative stress-induced endothelial dysfunction and up-regulated
      RhoA/Rho kinase activity, and both are the diseases at different stages of the
      pathological process of vascular dysfunction. Thus, it is particularly important
      to conduct regular and meticulous evaluation of such patients, so as to give
      rational individualized medication. Phosphodiesterase-5 inhibitors have an
      excellent efficacy and safety profile in the management of hypertension, either
      used alone or with antihypertensive medication. At present, gene therapy and
      adipose-derived stem cell therapy have displayed favorable prospects in the
      management of ED and hypertension, and translational medicine may help bring more
      clinical benefits.

PMID- 21898988
TI  - [Two single nucleotide polymorphisms on chromosome 3 and the risk of prostate
      cancer in Chinese men].
AB  - OBJECTIVE: To investigate the correlation of the common variant single nucleotide
      polymorphisms (SNP) on chromosome 3 with the incidence and related risk factors
      of prostate cancer (PCa) in Chinese men. METHODS: Using the case-control meth-
      od, we included 124 PCa patients in the PCa group and 111 age- and gender-matched
      cancer-free healthy subjects as normal controls. We detected the distribution of
      allele and genotype frequencies of the SNP rs10934853 and rs2660753 with the
      polymerase chain reaction-high resolution melting curve (PCR-HRM) combined with
      gene sequencing, analyzed the cumulative effect of the risk genotypes of these
      two independent variants, and determined the correlation between different
      genotypes of these two SNPs and clinically related risk factors in the PCa
      patients. RESULTS: As for the genotypes of rs10934853, there were 28 cases of AA
      (22.8%), 46 cases of CC (37.4%), and 49 cases of AC (39.8%) in the PCa patients,
      as compared with 24 (22.0%), 34 (31.2%) and 51 (46.8%) in the healthy controls.
      As regards the genotypes of rs2660753, there were 13 cases of AA (11.0%), 59
      cases of GG (50.0%) and 46 cases of AG (39.0%) in the PCa patients, in comparison
      with 9 (8.8%), 47 (45.6%) and 47 (45.6%) in the controls. No significant
      differences were found in the distribution of the genotype and allele frequencies
      of rs10934853 and rs2660753 between the two groups (P = 0.520 & 0.582). Analysis
      on the cumulative effect of the risk genotypes of rs10934853 and rs2660753 showed
      a slightly higher risk of PCa (OR = 1.831 & 1.968) in the two groups with risk
      genotypes than in the one with wild types (P > 0.05). Different genotypes of
      rs10934853 and rs2660753 were not correlated with clinically related risk factors
      of the PCa patients (P > 0.05). CONCLUSION: SNP rs10934853 and rs2660753 on
      chromosome 3 are not obviously correlated with PCa in Chinese patients, and may
      not be a genetic risk factor of PCa.

PMID- 21898989
TI  - [Pulmonary fibrosis induces erectile dysfunction in rats].
AB  - OBJECTIVE: To study the impact of pulmonary fibrosis on erectile function in rats
      and its mechanism. METHODS: Forty 12-week-old healthy male SD rats were randomly
      divided into Groups A (4-week pulmonary fibrosis), B (6-week pulmonary fibrosis),
      C (4-week control, and D (6-week control). The models of pulmonary fibrosis were
      established by injection of bleomycin at 5 mg/kg in the trachea, while the
      controls were injected with normal saline only. At 4 and 6 weeks, all the rats
      were subjected to determination of the serum testosterone (T) level, arterial
      blood gas analysis, measurement of intracavernous pressure/mean arterial pressure
      (ICP/MAP), and examination of NOS activity and cGMP content. The mRNA expressions
      of eNOS, iNOS and nNOS in the corpus cavernosum penis were detected by real-time
      PCR, and that of eNOS analyzed by Western blot. RESULTS: The 3 V and 5 V of the
      ICP/mapx100 in Group C were 16.37 +/- 2.19 and 27.19 +/- 3.18, significantly
      lower than 30.78 +/- 2.66 and 50.09 +/- 6.97 in Group A (P < 0.05); those in
      Group D were 10.17 +/- 1.31 and 17.40 +/- 1.74, significantly lower than 31.45 +/
      3.07 and 51.23 +/- 7.23 in Group B (P < 0.05), and so were they in Group D than
      in C (P < 0.05). PaO2 was significantly lower in Group C than in A ([75.50 +/-
      13.87] mmHg vs [103.80 +/- 6.88] mmHg, P < 0.05) , and so was it in Group D than
      in B ( [83.60 +/- 5.50] mmHg vs [102.70 +/- 5.77] mmHg, P < 0.05). Group C showed
      a significantly increased serum T level as compared with A ([391.1 +/- 264.7]
      ng/dl vs [175.9 +/- 53.0] ng/dl, P < 0.05), so did Group D ([745.4 +/- 408.8]
      ng/dl) versus Group B ([177.8 +/- 52.3] ng/dl) and C (P < 0.05). NOS activity and
      cGMP content in the corpus cavernosum significantly decreased in Group C ([1.50
      +/- 0.14] U/mg prot and [35.69 +/- 3.64] pmol/mg) compared with A ([2.66 +/-
      0.39] U/mg prot and [51.10 +/- 7.22] pmol/mg) (P < 0.05), so did they in D ([1.40
      +/- 0.20] U/mg prot and [34.55 +/- 4.30] pmol/mg) versus B ([2.75 +/- 0.36] U/mg
      prot and [52.15 +/- 6.86] pmol/mg) (P < 0.05), but neither showed any significant
      difference between Groups D and C (P > 0.05). The expression of the eNOS protein
      was significantly lower in Group C than in A (0.79 +/- 0.01 vs 0.87 +/- 0.01, P <
      0.05), so was it in D than in B and C (0.71 +/- 0.02 vs 0.88 +/- 0.01 and 0.79 +/
      0.01, P < 0.05). The expression of eNOS mRNA was significantly higher in Group C
      than in A (4.46 +/- 0.92 vs 2.61 +/- 0.68, P < 0.05), but did not show any
      significant difference between D and B (2.79 +/- 0.60 vs 2.69 +/- 0.65, P >
      0.05), nor did the expressions of nNOS mRNA and iNOS mRNA between the pulmonary
      fibrosis groups and the controls (P > 0.05). CONCLUSION: Pulmonary fibrosis may
      induce erectile dysfunction by suppressing the expression of the eNOS protein and
      reducing NOS activity and cGMP content in the corpus cavernosum penis of rats.

PMID- 21898990
TI  - [Differentially expressed genes in asthenospermia: a bioinformatics-based study].
AB  - OBJECTIVE: To study the differentially expressed genes in asthenospermia to gain
      a deeper insight into the molecular mechanisms of the disease. METHODS: We
      analyzed the differentially expressed genes in asthenospermia using GATHER,
      PANTHER and ToppGene online bioinformatics tools. RESULTS: Our bioinformatics
      mining and analyses revealed that the differentially expressed genes in
      asthenospermia played important roles in the cellular protein and macromolecular
      metabolism, protein modification, cell death, cell apoptosis and apoptosis
      induction. CONCLUSION: Asthenospermia patients experience a decline in sperm
      activity and the basic life activities of sperm simultaneously, and are also
      prone to cell apoptosis or death. Such differentially expressed genes as KIF3B,
      MYO15A, KIF6, KIF26B, KIF3A, DNHD2, DMN, DYNC2H1, STARD9, MYOHD1, and TPM1, which
      are involved in cytoskeletal structure, microtubule movement and cell movement,
      may be associated with asthenospermia, and therefore deserve further studies.

PMID- 21898991
TI  - [Expression of SEPT4 protein in the ejaculated sperm of idiopathic
      asthenozoospermic men].
AB  - OBJECTIVE: To investigate the role of the SEPT4 protein in the pathogenesis of
      idiopathic asthenozoospermia. METHODS: Samples of ejaculated sperm from
      idiopathic asthenozoospermia patients and normozoospermic men were separated and
      purified by Percoll discontinuous density gradients, the distribution and
      expression of SEPT4 in the sperm samples were determined by immunocytochemistry,
      and the expressions of SEPT4 mRNA and SEPT4 protein were detected by RT-PCR and
      Western blot. RESULTS: Immunocytochemistry showed that the expression of SEPT4,
      located in the annulus, was significantly reduced in the sperm of the idiopathic
      asthenozoospermia patients (t = 3.452, P < 0.01). RT-PCR revealed that the
      expression of SEPT4 mRNA was significantly lower in the sperm of the idiopathic
      asthenozoospermia patients than in those of the normozoospermic men (t = 3.521, P
      < 0.05). Western blot confirmed the results of RT-PCR (t = 5.872, P < 0.05).
      CONCLUSION: The expression of SEPT4 is significantly decreased in the ejaculated
      sperm of idiopathic asthenozoospermia patients, which might be one of the causes
      of idiopathic asthenozoospermia.

PMID- 21898992
TI  - [Changes in prostatic stromal composition and benign prostatic hyperplasia].
AB  - OBJECTIVE: To investigate whether there are different stromal compositions in the
      prostate tissue of patients with benign prostatic hyperplasia (BPH) and evaluate
      their significance in the course of the disease. METHODS: Forty-three surgical or
      bioptic prostatic specimens of BPH and 5 autoptic normal prostatic specimens were
      stained by the Masson method to display the elements of the muscle fiber and
      collagen. The relationship of the changes in the prostatic stromal composition
      was analyzed with the degree of bladder outlet obstruction (BOO) , IPSS and
      medication results. RESULTS: The mean ratio of muscle fiber to collagen in the
      normal prostate tissue was (3.2 +/- 0.2):1, significantly higher than that of the
      BPH patients (1: [4.7 +/- 3.1] ) (P < 0.01); that in the BPH patients with BOO
      was 1: (5.4 +/- 3.7) markedly lower than in those without BOO (1: [2.5 +/- 1.1] )
      (P = 0.02); that in the BPH patients with severe prostatic symptoms was 1: (9.1
      +/- 2.9), remarkably lower than in those with moderate (1: [5.3 +/- 3.4]) and
      mild prostatic symptoms (1: [2.8 +/- 1.7]) (P < 0.01); and that in the BPH
      patients with satisfactory medicinal therapeutic results was 1:(2.3 +/- 1.9),
      significantly higher than in those with poor therapeutic results (1: [7.6 +/-
      4.3]) (P < 0.01). CONCLUSION: The stromal composition in the prostatic tissue of
      BPH patients undergoes different degrees of changes. More obvious BPH symptoms
      and poorer therapeutic results are associated with a bigger proportion of
      collagens and a smaller proportion of muscle fibers in the prostatic tissue.
      These changes may play an important role in the development and progression of
      BPH.

PMID- 21898993
TI  - [Association of IL-6-572C > G polymorphism with the susceptibility to prostate
      cancer in the Chinese Han population in Jiangsu and Anhui area].
AB  - OBJECTIVE: To investigate the association of the IL-6 -572C > G polymorphism with
      the risk of prostate cancer (PCa) in the Chinese Han population in Jiangsu and
      Anhui area. METHODS: We obtained peripheral blood genome DNA from 200 PCa
      patients and 279 age-matched PCa-free healthy controls, analyzed the site
      polymorphism of IL-6 -572C > G with the polymerase chain reaction-restriction
      fragment length polymorphism (PCR-RFLP) technique, and studied the correlation of
      different genotypes with the susceptibility to PCa. RESULTS: The subjects that
      carried the CCGG genotype had a risk of PCa 2.46 times that of the CC genotype
      carriers (95% CI = 1.41-4.29), and 2.47 times that of the CC/GC genotype carriers
      (95% CI = 1.47-4.17). This risk was significantly increased among the following
      subgroups of CCGG genotype carriers: age > 70 yr (OR = 3.06, 95% CI: 1.44-6.49),
      BMI > 23 kg/m2 (OR = 3.72, 95% CI: 1.79-7.74), no cigarette smoking (OR = 2.96,
      95% CI: 1.30-6.72), alcohol drinking (OR = 2.73, 95% CI: 1.28-5.79), with a
      family history of cancer (OR = 6.67, 95% CI: 1.50-29.69). CONCLUSION: In the
      Chinese Han population in Jiangsu and Anhui area, IL-6 -572C > G polymorphism is
      associated with the susceptibility to PCa, and GG might be a susceptible genotype
      to PCa.

PMID- 21898994
TI  - [Expression of heme oxygenase enzyme in the testis tissue and azoospermia].
AB  - OBJECTIVE: To investigate the location of heme oxygenase (HO) enzyme in the human
      testis, and explore the correlation of the expression of HO enzyme with
      azoospermia by analyzing its different expression levels in the testes of
      nonobstructive azoospermia, obstructive azoospermia and normal men. METHODS: We
      detected the location of the cells expressing HO enzyme in the human testis
      tissue using immunohistochemistry, determined the mRNA and protein expression
      levels of HO-1 and HO-2 in the testes of azoospermia patients and normal healthy
      men by RT-fluorescence quantitative PCR (RT-FQ-PCR) and Western blot, and
      explored the correlation of HO expressions with the pathogenesis of azoospermia.
      RESULTS: HO-1 enzyme was expressed mainly in the Sertoli cells and HO-2 enzyme
      chiefly in the germ cells of the testis tissue. RT-FQ-PCR showed that the
      expression of HO-1 in the testis tissue was significantly lower in the
      nonobstructive azoospermia than in the normal and obstructive azoospermia groups
      (P < 0.05), with no significant difference between the latter two. Western blot
      revealed no obvious difference between the expression level of HO-1 protein and
      that of HO-1 mRNA. There were no differences in the expression level of HO-2
      protein among the three groups. CONCLUSION: The expression level of HO enzyme is
      significantly decreased in the testis tissue of nonobstructive azoospermia
      patients, and the expression of HO-1 protein is consistent with that of HO-1
      mRNA. As HO-1 protects the testis tissue against various stress injuries through
      its antioxidant, anti-inflammatory and anti-apoptotic effects, its decreased
      expression level may be correlated with spermatogenic dysfunction, and therefore
      considered as a possible mechanism of nonobstructive azoospermia.

PMID- 21898995
TI  - [Relationship between the levels of sex hormones and loss of bone mass in aging
      male rats].
AB  - OBJECTIVE: To investigate the relationship between the level of sex hormones and
      the loss of bone mass in aging male rats. METHODS: Thirty male Sprague-Dawley
      rats were equally divided into five age groups and sacrificed at 35, 70, 160, 700
      and 800 postnatal days (PD) , followed by measurement of the % Tb x Ar, Tb x Th,
      Tb x N and Tb x SP by bone histomorphometry and detection of the levels of serum
      testosterone (T) and estradiol (E2) by radioimmunoassay. The relationship between
      the changes of the T and E2 levels and those of bone histomorphometry was
      analyzed. RESULTS: T and E2 levels were closely correlated with the bone mass in
      the aging male rats. The changes in T and E2 levels were simultaneous with those
      in the bone mass with the growth of the rats. T, E2, % Tb x Ar and Tb x N reached
      the peak in the 70 and 160 PD groups, and markedly decreased in the 700 PD group
      except Tb x Th and Tb x SP. The T levels in the 35, 70, 160, 700 and 800 PD
      groups were (118.53 +/- 18.35) ng/dl, (345.49 +/- 54.63) ng/dl, (368.83 +/-
      60.03) ng/dl, (61.15 +/- 21.12) ng/dl and (60.35 +/- 19. 27) ng/dl, changing
      simultaneously with the E2 levels, which were (10.35 +/- 1.82) pg/ml, (16.92 +/-
      3.13) pg/ml, (17.20 +/- 2.51) pg/ml, (5.87 +/- 2.34) pg/ml and (5.53 +/- 2.48)
      pg/ml, respectively. The metrological parameters of the bone structure in the
      five groups were as follows, Tb x Ar: (19.52 +/- 2.23)%, (26.28 +/- 2.18) %,
      (28.37 +/- 1.21) %, (15.62 +/- 1.68) % and (14.21 +/- 0.89) %; Tb x Th: (35.45 +/
      1.63) microm, (50.13 +/- 3.58) microm, (60.23 +/- 8.25) microm, (75.62 +/- 9.72)
      microm and (78.78 +/- 11.21) microm; Tb x N: (5.98 +/- 1.21) n/mm, (8.07 +/-
      0.86) n/mm, (8.30 +/- 1.22) n/mm, (2.63 +/- 1.35) n/mm and (2.48 +/- 1.62) n/mm;
      Tb x SP: (126.34 +/- 18.15) microm, (136.26 +/- 15.27) microm, (261.08 +/- 76.43)
      microm, (323.12 +/- 78.12) microm and (330.23 +/- 50.20) microm. CONCLUSION:
      Changes in the levels of sex hormones are closely correlated with those of bone
      mass. Both testosterone and estradiol are essential for bone development and bone
      mass maintenance.

PMID- 21898996
TI  - [Prevalence of sexual dysfunction in old and middle-aged males in Pingliang
      area].
AB  - OBJECTIVE: To investigate the prevalence of hyposexuality, erectile dysfunction
      (ED) and defective ejaculation (DE) in the old and middle-aged males in Pingliang
      area. METHODS: This investigation included 1 539 men aged > or = 50 years from 6
      urban districts and 20 villages in the suburbs of Pingliang City, Gansu Province.
      We recorded and analyzed their scores on IIEF-5 and Brief Male Sexual Function
      Inventory for Urology (O'Leary 1995). RESULTS: A total of 1 230 subjects met the
      investigation criteria. They averaged 62.5 +/- 9.6 years of age (range 50-89
      years), and were divided into four age groups: 50-59, 60-69, 70-79 and > or = 80
      years. The mean scores on IIEF-5 were 0-25 (9.4 +/- 8.6), sexual desire 0-8 (2.3
      +/- 2.1), and ejaculation 0-8 (3.6 +/- 3.0). Hyposexuality, ED and DE were
      defined as sexual desire score < or = 2, IIEF-5 score = 0-21, and ejaculation
      score < or = 2, respectively. Based on these criteria, the incidence rates of
      hyposexuality, ED and DE were 57.96%, 92.27% and 36.91%, respectively, with
      statistically significant differences among different age groups (P < 0.01).
      CONCLUSION: The prevalence of ED, hyposexuality and DE, particularly the
      incidence of ED, is positively correlated with the increase of age in the old and
      middle-aged males in Pingliang area.

PMID- 21898997
TI  - [Male urethral duplication infection: experience with 9 cases].
AB  - OBJECTIVE: To study the clinical characteristics of male urethral duplication
      infection and offer some guidelines for the diagnosis and treatment of the
      disease. METHODS: We analyzed the pathological types, clinical characteristics,
      therapeutic processes and follow-up results of 9 cases of male urethral
      duplication. RESULTS: Among the 9 cases of urethral duplication, 7 turned out to
      be of Type I, 1 Type II A2 and 1 Type II B. The disease courses varied from 2 to
      420 days, with an average of 77.2 +/- 141.5 days. Four cases with longer disease
      duration were identified with a history of repeated use of various antibiotics
      for treatment. Their clinical manifestations varied, with the outflow of
      excretions or pus from the duplicate or normal urethra as the cardinal symptoms.
      The pathogens detected from the secretions were mainly Neisseria gonorrhoeae,
      Ureaplasma urealyticum, and Chlamydia trachomatis. The consistency rate of the
      same pathogens detected in the vaginal or cervical secretions from the sex
      partners of the patients was 87.5%. All the symptoms disappeared after a
      sufficient-course treatment with sensitive antibiotics, and the patients' sex
      partners received the same medication simultaneously. No recurrence was found
      during a 3-month follow-up. CONCLUSION: Urethral duplication infection has
      various clinical manifestations, and thus is easily missed in diagnosis.
      Sufficient-course treatment with sensitive antibiotics is recommended for those
      that prefer conservative therapy, and their sex partners should be treated
      simultaneously.

PMID- 21898998
TI  - [Large cell calcifying Sertoli cell tumor of the testis: a clinicopathological
      observation].
AB  - OBJECTIVE: To investigate the clinicopathological characteristics of large cell
      calcifying Sertoli cell tumor (LCCSCT) of the testis. METHODS: We studied a case
      of LCCSCT by light microscopy, Western blotting and immunohistochemistry,
      reviewed relevant literature, and analyzed the clinical, morphological and
      immunohistochemical features, treatment and prognosis of the tumor. RESULTS: The
      patient was a 25 years old man. Pathohistologically, the tumor was characterized
      by a mass of polygonal tumor cells in a tubular and trabecular growth pattern,
      with abundant acidophilic cytoplasm, enlarged vesicular nuclei, and extensive
      calcified debris in stroma. The tumor cells were positive for inhibin, S-100,
      vimentin and alcian blue, but negative for PLAP, SMA, CK, AFP and periodic acid
      Schiff (PAS) reaction. CONCLUSION: LCCSCT is a rare testicular sex cord stromal
      tumor. Its diagnosis is based on immunohistochemical staining, and it is to be
      differentiated from other lesions of the testis, including seminoma, Leydig cell
      tumor, Sertoli cell node, and androgen insensitivity syndrome. For the treatment
      of LCCSCT, surgical resection often has a good prognosis.

PMID- 21898999
TI  - [Endothelial injury and erectile dysfunction].
AB  - The endothelium plays an important role in maintaining vascular homeostasis,
      regulating vascular tone and blood flow, and preserving a non-thrombogenic blood
      tissue interface, and the normal function of the vascular endothelium is
      essential for penile erection. In most cases, erectile dysfunction (ED) is
      accompanied by endothelial dysfunction, and endothelial injury is a major
      pathological basis of ED, which can be induced by bad lifestyles, cardiovascular
      diseases, reactive oxygen species, and inflammatory mediators. The vascular
      endothelium is capable of self-repairing, and endothelial injury results from the
      unbalanced factors of injury and repair. This review focuses on the mechanism and
      repair of endothelial injury and the relationship of endothelial injury with ED.

PMID- 21899000
TI  - [Brain mechanisms of male sexual function].
AB  - In this paper, we reviewed the brain imaging studies of male sexual function in
      recent years from three aspects: the brain mechanism of normal sexual function,
      the brain mechanism of sexual dysfunction, and the mechanism of drug therapy for
      sexual dysfunction. Studies show that the development stages of male sexual
      activities, such as the excitement phase, plateau phase and orgasm phase, are
      controlled by different neural networks. The mesodiencephalic transition zone may
      play an important role in the start up of male ejaculation. There are significant
      differences between sexual dysfunction males and normal males in activation
      patterns of the brain in sexual arousal. The medial orbitofrontal cortex and
      inferior frontal gyrus in the abnormal activation pattern are correlated with
      sexual dysfunction males in sexual arousal. Serum testosterone and morphine are
      commonly used drugs for male sexual dysfunction, whose mechanisms are to alter
      the activating levels of the medial orbitofrontal cortex, insula, claustrum and
      inferior temporal gyrus.

PMID- 21899001
TI  - [Regulatory effect of Bushenfang on the serum testosterone level of naturally
      aging rats and its mechanism].
AB  - OBJECTIVE: To study the regulatory effect of Bushenfang on the serum testosterone
      (T) level of naturally aging rats and its mechanism, in order to provide a
      theoretical and experimental basis for the clinical treatment of late onset
      hypogonadism (LOH) in males. METHODS: Thirty-two 18-month-old male SD rats were
      randomly divided into four groups of equal number, naturally aging model and low
      , medium- and high-dose Bushenfang groups, and another eight 4-month-old rats
      were taken as normal controls. The rats of the aging model and normal control
      groups were treated with normal saline, while those of the low-, medium- and high
      dose Bushenfang groups received intragastrically Bushenfang at 3.25, 7.50 and
      15.00 g/kg, respectively, all for 3 weeks. Then the rats were sacrificed, the
      histomorphologic changes of the testis observed by HE staining, the serum T level
      measured by radioimmunoassay, and the expressions of the StAR protein, P450scc
      and 3beta-HSD I determined by RT-PCR. RESULTS: The number of Leydig cells was
      obviously increased after Bushenfang treatment. The levels of serum T were
      significantly higher in the low-, medium- and high-dose Bushenfang groups ([6.74
      +/- 1.56] nmol/L, [8.50 +/- 1.99] nmol/L and [12.41 +/- 2.91] nmol/L) than in the
      model group ([3.48 +/- 0.75] nmol/L) (P < 0.05). The three Bushenfang groups also
      showed a remarkable elevation in the mRNA expressions of StAR (0.74 +/- 0.29,
      0.83 +/- 0.32 and 1.35 +/- 0.50), P450scc (0.72 +/- 0.36, 1.023 +/- 0.30 and 1.41
      +/- 0.37) and 3beta-HSD I (0.58 +/- 0.14, 0.72 +/- 0.07 and 0.85 +/- 0.18), as
      compared with the models (StAR: 0.44 +/- 0.09; P450scc: 0.33 +/- 0.05; 3beta-HSD
      I: 0.34 +/- 0.02), with significant differences in the StAR expression between
      the high-dose Bushenfang and the model groups, as well as in P450scc and 3beta
      HSD I expressions between the medium- and high-dose Bushenfang and the model
      groups (P < 0.05). CONCLUSION: Bushenfang could improve the pathological status
      of testicular injury and increase the expression of testosterone synthetase,
      which might be the mechanism behind its regulatory effect on the serum T level of
      aging rats.

PMID- 21899002
TI  - [Relationship between RNA degradation and postmortem interval in mice].
AB  - OBJECTIVE: To investigate the degradation changes of beta-actin mRNA and 18S rRNA
      in different time points and temperature after death, and to explore the
      relationship between the changes and postmortem interval (PMI) in the brain of
      mice. METHODS: Twenty-four health adult C57BL/6 mice were randomly divided into
      two groups (12 each group). They were sacrificed by cervical dislocation and
      placed in chamber with two different temperature (4 degrees C and 37 degrees C,
      humidity was 80%). The mice brains were sampled at 6 different time
      points(immediately, 0.5h, 2h, 6h, 24h, 48h), and total brain RNA were extracted.
      Ct value of each sample was obtained using RT-PCR and real-time PCR technology,
      and beta-actin mRNA and 18S rRNA content ratio was calculated. The correlation
      between the content ratio and PMI was expressed using statistical regression
      analysis. RESULTS: At 37 degrees C, RNA degradation rate was faster than 4
      degrees C, which showed that there was correlation between temperature and RNA
      degradation. Comparing with the stability of beta-actin mRNA, 18S rRNA was more
      stable. CONCLUSION: The study on degradation of beta-actin mRNA and 18S rRNA in
      mice brain using real time PCR technology could provide a new theoretical basis
      for estimation of PMI and would be supplementary to the traditional methods.

PMID- 21899003
TI  - [Effect and mechanism of intermedin in acute rat cardiac ischemic injury].
AB  - OBJECTIVE: To investigate the effect and potential mechanism of intermedin (IMD)
      in acute cardiac ischemic injury and to provide a new approach for exploring
      mechanism of sudden cardiac death. METHODS: Seventy-two healthy male rats were
      randomly divided into 3 groups: control, ischemic and the IMD-treated group. The
      activity of lactate dehydrogenase (LDH), malondialdehyde (MDA) and superoxide
      dismutase (SOD) in heart blood were tested by enzyme chemistry method. The mRNA
      changes of calcitonin receptor-like receptor (CRLR) and receptor activity
      modifying proteins (RAMPs) in cardiac were measured by real-time PCR analysis.
      Myocardial cyclic adenosine monophosphate (cAMP) content was determined by enzyme
      linked immunosorbent assay (ELISA). Apoptosis related factors Bcl-2 and Bax were
      detected by immunohistochemistry. RESULTS: Comparing with the control group, LDH
      and MDA activity of ischemic group in heart blood increased and SOD activity
      decreased. The concentration of cAMP increased in ventricular muscle, Bcl-2 and
      Bax proteins expression ratio level decreased. The intravenation of IMD decreased
      the level of increased activity of LDH and MDA, and lessened the level of
      decreased activity of SOD. The mRNA expression of CRLR and RAMPs obviously
      increased in ventricular muscle. CONCLUSION: The protective effect of IMD against
      myocardial ischemic injury could be caused by decreasing the oxidative stress of
      ischemia and inhibiting the myocardial apoptosis.

PMID- 21899004
TI  - [Iron and ferritin changes in multiple organs failure after trauma].
AB  - OBJECTIVE: To investigate the changes of iron content in serum and liver,
      ferritin content in serum, percentage of myeloperoxidase (MPO) positive
      granulocyte in rabbits after different serious trauma and to explore the
      relationship between these changes and multiple organ failure (MOF). METHODS:
      Rabbit trauma models were established. Iron content in serum and liver, ferritin
      content in serum and the percentage of MPO positive granulocyte were measured at
      different time after trauma. RESULTS: After trauma, iron content in serum
      decreased sharply in early period (12-36h) and increased gradually to normal
      level in mild traumatic group after 60 h. Iron content in serum remained lower
      level in severe traumatic and death group 60 h after trauma. Iron content in
      liver obviously increased in death group. The changes of ferritin content in
      serum in mild traumatic were not obvious. Ferritin contents in serum in severe
      injury group and death group were slightly higher in early period and decreased
      in later period. The percentage of MPO positive granulocyte increased in early
      period after trauma. The percentage began to decrease 6 d after trauma and
      returned to normal level in mild traumatic group. The percentage obviously was
      significantly lower than normal levels in severe traumatic group and death group
      6 d after trauma. Some rabbits died 60 h-6 d after severe trauma, and the
      pathological changes in the other organs were consistent with MOF. CONCLUSION:
      Trauma can cause the serum iron, ferritin levels and percentage of MPO positive
      granulocyte changes. Severe trauma can cause uncompensated changes of these
      indicators, which could be the main mechanisms of MOF and death.

PMID- 21899005
TI  - [Ultra-structural pathological study of pulmonary fat embolism in rabbits].
AB  - OBJECTIVE: To explore ultra-structural changes of fat embolism syndrome (FES) in
      the lung. METHODS: Fat embolism animal model was developed by fat intravascular
      injection to the experimental rabbits. The rabbits were sacrificed after
      thrombosis immediately (0 h), 3 h, 8 h and 1 d, 2 d, 7 d, 14 d after thrombosis,
      respectively. Rabbits were injected with the same dose of saline in the control
      group. All experimental procedures were same in experimental and control groups.
      The animal model of fat embolism was validated using HE and Sudan III staining.
      Ultra-structural changes of lung were observed by using transmission electron
      microscopy. RESULTS: Ultra-structural changes in capillaries and small blood
      vessels were found in experimental group. Type II alveolar cells, related cells
      and organelles showed time-dependent changes. Lipid drops and inflammatory cells
      were not found in control group. Lamellar body did not show emptying phenomenon
      and the amount of lamellar body was normal. CONCLUSION: The study could provide
      the theoretical principle for fat embolism casesin forensic pathology.

PMID- 21899006
TI  - [Stature estimation of teenagers by limb long bones with computerized
      radiography].
AB  - OBJECTIVE: Relative parameters of upper limb bones, tibia and fibula were
      measured with computed radiography and used to establish the mathematical models
      for stature estimation of teenagers (from 14 to 18 years old) of Han population
      in Sichuan Province. METHODS: The upper limb bones, tibia and fibula of 194
      subjects were taken computerized radiography on normal position and were measured
      the lengths between relative landmarks. The body height of each subject was
      recorded. Linear regression equations for stature estimation between body height
      and the lengths of upper limb bones, tibia and fibula were established. RESULTS:
      Forty-two single linear regression equations and 4 multiple regression equations
      were obtained. The coefficients of correlation(r) were 0.689-0.917 and the
      standard errors of estimate(SE) were between 3.075 and 5.485 cm. All of the
      equations were statistically tested and diagnosed with good applicability.
      CONCLUSION: These equations could be used to estimate the body height of Sichuan
      Han population aged from 14 to 18. The lengths of the upper limb bones, tibia and
      fibula measured on the CR films could be useful to stature estimation of the
      adolescence and the forensic personal identification.

PMID- 21899007
TI  - [Application of slow vertex response in auditory threshold prediction for
      subjects with hearing loss].
AB  - OBJECTIVE: To study the value of slow vertex response (SVR) in the evaluation of
      hearing loss by comparing the hearing thresholds acquired with SVR and pure tone
      audiometry (PTA). METHODS: Twenty-five subjects (40 ears) with sensorineural
      hearing loss were tested by PTA and SVR. According to the thresholds of PTA,
      these ears were subdivided into mild, moderate and severe hearing loss groups,
      and rank sum test was performed on the thresholds of SVR and PTA for all the
      hearing loss groups. Then, the correlation between PTA thresholds and SVR
      thresholds was analyzed and the mathematical models were established for
      predicting behavioral thresholds by the thresholds of SVR. RESULTS: At four test
      frequencies (0.5, 1, 2 and 4kHz), the thresholds of SVR had high correlations
      with thresholds of PTA. Four liner regression equations were established, and the
      correlation coefficient(r) were 0.971, 0.976, 0.957 and 0.928, respectively (P <
      0.05). Back substitution test showed that the liner regression equations would be
      an easy method for estimating the behavior thresholds. CONCLUSION: The behavioral
      threshold can be well judged and evaluated by the liner regression equations
      established with SVR thresholds.

PMID- 21899008
TI  - [Polymorphism study of small nuclear ribonucleoprotein polypeptide N gene
      rs220030 by DGGE].
AB  - OBJECTIVE: To analyze the polymorphism of rs220030, a SNP which is located in the
      promoter region of small nuclear ribonucleoprotein polypeptide N (SNRPN) gene in
      the Chinese Han population and to obtain the data of population genetics.
      METHODS: The denaturing gradient gel electrophoresis (DGGE) method was applied to
      detect the polymorphism of rs220030 in 100 unrelated and healthy individuals from
      the Shanghai Han population. The genotyping result of this SNP was confirmed by
      TaqMan assay in some typical samples. RESULTS: DGGE results showed 4 bands for CT
      heterozygote, and 1 band for CC or TT homozygote, and those results were
      confirmed by The TaqMan SNP genotyping assays. Genotyping results showed 34
      individuals with CC, 41 with CT and 25 with TT of rs220030. The allele
      frequencies for C and T were 0.545 and 0.455, respectively. H was 0.500, PIC was
      0.373, DP was 0.654, and PE was 0.186. The distribution of genotype frequencies
      were in Hardy-Weinberg equilibrium. CONCLUSION: DGGE is a quick and effective
      method in the analysis of SNP polymorphism in small population. Statistical
      parameters of rs220030 for forensic evaluation meet the requirements for forensic
      identification and paternity testing.

PMID- 21899009
TI  - [Application of WAIS-RC short forms and adult intelligence disability scale in
      mental impairment assessment].
AB  - OBJECTIVE: Study on the application of WAIS-RC short forms and adult intelligence
      disability scale in mental impairment assessment. METHODS: Mental impairment
      assessment cases between July 2009 and March 2011 in judicial appraisal institute
      of Taizhou University were collected. Assessment results obtained with the WAIS
      RC short forms and adult intelligence disability scale were compared with the
      experts assessing conclusions and analyzed using SPSS 11.5 software. RESULTS:
      Assessment results with the two scales did not fully comply with the expert's
      conclusions, with reliability coefficient were 0.785 and 0.940 respectively,
      correlation coefficient were 0.850 and 0.922 respectively. CONCLUSION: The
      intelligence assessment was influenced by many factors. When the appraised
      individuals had nerve dysfunction and mild intelligence disability or mental
      disorders, the two scales should be used together. When the appraised individuals
      had moderate intelligence disability or mental disorders, adult intelligence
      disability scale had advantage.

PMID- 21899010
TI  - [Determination of Hg in biological samples by inductively coupled plasma mass
      spectrometry].
AB  - OBJECTIVE: To establish an inductively coupled plasma mass spectrometry (ICP-MS)
      method for determination of Hg in biological samples. METHODS: The samples were
      digested with microwave digestion instrument. ICP-MS was applied to detect Hg in
      blood, urine and hair specimens by using 115In as an internal marker. The ability
      of gold to eliminate the memory effect of mercury was investigated with the gold
      amalgamate produced by gold and mercury. RESULTS: The limits of detection were in
      the 0.01 microg/L, and the accuracy of the method ranged from 97.0% to 107.1%.
      The concentration of gold was 10 microg/L and the memory effect of mercury was
      resolved. CONCLUSION: The method is accurate, rapid, sensitive and suitable for
      the cases of mercury poisoning and the clinical diagnosis and monitoring for
      patients with mercury poisoning.

PMID- 21899011
TI  - [Criminological characteristics of female violent criminal suspects].
AB  - OBJECTIVE: To study criminological characteristics of female violent criminal
      suspects who accepted forensic psychiatry assessment. METHODS: Information of the
      suspects involved in judicial appraisal between 2000 and 2009 were collected and
      analyzed according to our self-made scale. RESULTS: The age of 259 suspects were
      between 16 and 81 years old. There were 205 (79.2%) suspects who were younger
      than 45 years old. There were 225 (86.9%) suspects who were married. There were
      14 different appraisal results: schizophrenia 47.1%, without psychosis 15.4%,
      depression 10.4% and others 27.1%. Irresponsibility involved with 59.5%, partial
      responsibility 18.5% and full responsibility 22.0%. Murder were 85.7%, arson
      10.4%, inflicted injury 1.9% and robbery 1.9%. A total of 191 cases resulted in
      death, accounting for 82.3% of all cases. In 34.9% of all cases, the victims were
      male spouse of the suspects. Main weapons used in the crime were cutters and
      other working related tools (36.3%). There were 66.8% of all cases were with
      pathological motivation, 29.7% with reality motivation and 3.5% cases were with
      unknown motivation. CONCLUSION: Female violent suspects in our cases often
      suffered from various kinds of mental diseases. Their motivations were
      pathological primarily. Most cases were intentional killing with family members
      as victim mainly. Major weapons used were daily working related tools.

PMID- 21899012
TI  - [Comparative analysis of 607 autopsy cases of poisoning death].
AB  - OBJECTIVE: To provide references for forensic expertise by investigating the
      kinds of toxicant, routes of exposure and manners of poisoning deaths, etc.
      METHODS: Six hundred and seven autopsy cases of poisoning deaths from 1957 to
      2008 in Department of Forensic Medicine, Tongji Medical College (Tongji Forensic
      Science Identification Center of Hubei), were comparatively reviewed. RESULTS: In
      218 cases from 1999 to 2008, more than 50% of decedents were male in the ages of
      30-49. The toxicants are usually taken orally and the most common manner of death
      was accidental. The common substances involved in poisoning death were
      rodenticide, poisoning gas and insecticide. Compared to the data of 1983-1998 and
      1957-1982, the common toxic agents had changed significantly. The number of cases
      involving insecticide and cyanide poisoning decreased in recent years, and the
      number of cases of rodenticide, poisoning gas, alcohols poisoning displayed an
      increase tendency, especially for drugs abuse. CONCLUSION: Poisoning deaths of
      pesticides remain a major public health problem for a long time and the awareness
      of prevention need to be raised, especially for the prevention of deaths from
      multiple poisons.

PMID- 21899014
TI  - [The best corrected presenting distance visual acuity in forensic medicine].
AB  - At present the sight impairment evaluation in forensic medicine of China is based
      on the international classification of disease by WHO in 1973. The main measured
      indicator is "best corrected visual acuity". It is different from "presenting
      distance visual acuity" in some situations. In the new blindness and vision loss
      classification made by WHO in 2003, "presenting distance visual acuity" took the
      place of the "best corrected visual acuity". In the practice of forensic
      medicine, "presenting distance visual acuity" can not reflect the real visual
      acuity duo to the exaggeration or disguise of the wounded. We suggest to use "the
      best corrected presenting distance visual acuity" instead of "presenting distance
      visual acuity" in order to avoid the influences of the exaggeration or disguise
      of the wounded.

PMID- 21899013
TI  - [Polymorphic analysis of 5 Y-SNP loci in Han population of Jinan].
AB  - OBJECTIVE: To investigate polymorphism distribution of the 5 Y-SNP loci in Jinan
      Han population, and evaluate their potential in forensic application. METHODS:
      Genotyping of 5 Y-SNP loci (M89, M9, M122, M134, M95) were executed in the sample
      of 103 unrelated Chinese male individuals in Jinan Han population by using
      fragment length discrepant allele specific PCR (FLDAS-PCR). RESULTS: In 5 Y-SNP
      loci, genetic polymorphism were identified in Jinan Han population, and the
      ranges of gene diversity(GD) were 0.093 3-0.491 2. Twenty different haplotypes
      were observed and the haplotypes diversity (HD) was 0.867 9. Six different
      haplogroups were detected according to international association of Y chromosome
      nomenclature. CONCLUSION: Five Y-SNP loci and their haplogroups in Jinan Han
      population are highly polymorphic, which can provide more information for the
      genetic structure analysis and forensic genetics research in the region.

PMID- 21899015
TI  - [The progress in the study on auditory evoked potentials].
AB  - Auditory evoked potential (AEP) is the electric activities originating from
      auditory systems evoked by sound stimulus. AEP include cortical electric response
      audiometry (CERA), auditory brainstem evoked response (ABR), 40 Hz auditory event
      related potentials (40 Hz AERP), auditory steady-state response (ASSR), etc. For
      the subjects who cannot provide reliable or accurate behavioral hearing
      threshold, those techniques have been explored to evaluate the behavioral hearing
      threshold objectively. These techniques are reviewed in this article and are
      found that they could reflect the behavioral hearing threshold very well. CERA is
      difficult to operate because it is affected by the subject's wakefulness. ABR is
      the most widely used method currently and is not affected by the subject's
      consciousness, but it only reflects high frequencies. 40 Hz AERP has good
      sensitivity, while its results highly depend on the subject's consciousness. ASSR
      can be operated by using multiple frequency stimuli simultaneously to both ears
      and the test time is short. It is still a very difficult task to combine
      different techniques according to their characteristics in forensic audiology.

PMID- 21899016
TI  - The general practitioner's challenge.

PMID- 21899017
TI  - Ready or not, here they come.

PMID- 21899018
TI  - Salivary diagnostics in medicine and dentistry: a review.

PMID- 21899019
TI  - Interdisciplinary management of implant overdenture therapy.

PMID- 21899020
TI  - The "first implant": protocol for the GP part I, treatment planning.

PMID- 21899021
TI  - Revolutionary advances, part 2: active disinfection.

PMID- 21899022
TI  - An efficient approach to full-mouth extractions.

PMID- 21899023
TI  - Treating fractured teeth with composite resin.

PMID- 21899024
TI  - Sonic activation: new paradigm for composite resins.

PMID- 21899025
TI  - Supragingival dentistry: a practical paradigm shift.

PMID- 21899026
TI  - Direct composite resin restorations: placement strategies.

PMID- 21899027
TI  - The diode laser in endodontics.

PMID- 21899028
TI  - [The dispanserization and public health in Russia. Report 2: The dispanserization
      technique as a tool of prevention approach in public health].
AB  - The issues of the development of medical social prevention based on the wide
      implementation of the dispanserization technique, the tool approved its
      effectiveness in the activities of public medical institutions. In the Soviet
      public health system, the dispanserization of economically active population
      implemented in the industrial enterprises, special dispensers and maternity and
      child welfare clinics. The abrupt transfer of Russian economics into the
      conditions of capitalist market occurred in early 1990s and resulted into the
      catastrophic decrease of the role of health units and medical sanitary units in
      the system of preventive medicine. Their totality at the enterprises decreased to
      63%, their bed-space decreased to 73.8% and the number of employed physician
      appointments decreased to 3.1 times. The medical sanitary units lost their access
      to such powerful financial institutes as ministry and enterprises budgets and
      system of mandatory medical insurance. Actually, the system of medical
      institutions providing curative preventive care to the workers of industrial
      enterprises is in the process of restoration. Their numbers is augmenting without
      consideration of the experience of nation public health and with no coordination
      with the general net of medical institutions of Ministry of Health. The
      implementation of the dispanserization as an organizational technique is a key
      target in development of model of preventive public health in modern Russia.

PMID- 21899029
TI  - [The characteristics of perception by patients from different countries the
      conditions of medical care provision].
AB  - The article demonstrates that with lesser demands of Russian population
      concerning various aspects of public health system functioning, as compared with
      population of Europe, the most tolerant to the actual conditions are elderly
      people, especially dwelling in the families with lower material income. This fact
      can be considered as a stimuli to enhance the corresponding aspects of health
      care system functioning.

PMID- 21899030
TI  - [The structural functional analysis of population attendance of physicians of
      ambulatory polyclinic institutions in the Russian Federation].
AB  - The article deals with the results of the structural functional analysis of
      population attendance of ambulatory polyclinic institutions in Russia. The
      purpose of the study consisted in determining in what medical institutions, to
      what scope, by what kind of specialists, no what groups of population and with
      what purpose the medical care is provided. It is proved that the numbers of
      patients' attendance per one inhabitant per year is a conditional mean value. The
      significant differences in scope and structure of poll-consumption of the
      ambulatory polyclinic care between adults and children, townsmen and countrymen
      indicate the different degree in demand in this care and its accessibility. It is
      demonstrated that in ambulatory polyclinic institutions.

PMID- 21899031
TI  - [The dynamics of population morbidity in the mining territories of Ural region].
AB  - The dynamics of the indicators of general and primary disease incidence are
      analyzed relating to the population dwelling in the territories of functioning of
      mining complexes of Ural during 2000-2007. The study revealed a number of
      unfavorable trends in the morbidity as compared with the overall region data.

PMID- 21899032
TI  - [The evaluation of attitude of patients with arterial hypertension to the disease
      and degree of physician recommendations observation].
AB  - The article deals with the issues of evaluation of to what degree the patients
      with arterial hypertension follow the recommendations of physicians concerning
      the self-control of arterial tension, the alteration of life-style to decrease
      the impact of risk factors, the regular intake of pharmaceuticals. The patients
      have been asked about how long ago they made the last measure on purpose to
      assess their responsibility concerning arterial hypertension control. The
      arterial tension was measured during the last six months in 76% of patients and
      during 6-11 months in 19% of patients. The arterial tension was measured by
      physician in 85% of patients, by feldsher (medical assistant) in 3% of patients,
      by nurse in 12% of patients, and 75% of patients were able to self-care in case
      of increase of arterial tension. The patients with arterial hypertension were
      informed about the measures to prevent the complication of arterial tension. The
      most of them don't follow the given recommendations. To successfully prevent the
      adverse outputs of arterial hypertension in patients it is necessary to recommend
      to each patient changing life-style and decreasing the impact of risk factors. To
      provide better care of patients with arterial hypertension enhancing of both
      dispanserization follow-up and functioning of health nurse is needed.

PMID- 21899033
TI  - [The systemic modification of regional public health system for enhancing
      availability and quality of population medical care].
AB  - The article deals with the main directions in modernization of public health
      system of Irkutskaya oblast in 2011-2012. The major indicators to evaluate the
      overall effectiveness and efficacy of the proposed modernization program are
      discussed. The measures proposed can promote the systemic settlement of regional
      public health problems, increase the availability and enhance quality of medical
      care to population.

PMID- 21899034
TI  - [The intersectoral approach to medical social care delivering to underaged
      children].
AB  - The model of infringements among neglected and homelessness under-aged children
      is used to demonstrate that in actual pattern of Russian social society the
      intersectoral partnership is the essential condition in overcoming the problems
      of youth generation. Nowadays, the most important target is the involvement in
      this process the youths themselves.

PMID- 21899035
TI  - [The assessment of the elderly patients' need in medical and social care during
      remission period].
AB  - The article considers the results of medical sociological survey of elderly
      patients with chronic therapeutic pathology. The issues of assessing the degree
      of provision of their medical and social needs during remission period are
      discussed. The sampling included 212 patients aged 65 years and older receiving
      medical and social care in health institutions of City of Kursk and Lipetskaya
      oblast. The social demographic profile of patient is defined. The shortcomings in
      rendering continuous pharmaceutical treatment, diet maintenance, organization of
      nursing and social care at home, rehabilitation activities.

PMID- 21899036
TI  - [The role of preventive activities in the process of disease prevention as an
      integral part of primary medical sanitary care].
AB  - The article deals with the study results related to preventive activities in the
      primary medical sanitary care system. It is demonstrated that the prevention
      activities of physicians are lacking of both proper organization and adequate
      involvement into the process. The medical personnel in the primary medical
      sanitary system need enhancing of professional qualification especially in the
      field of health promotion and disease prevention. The study proved the necessity
      of including the prevention into the actual health policy and health care
      planning.

PMID- 21899037
TI  - [The scientific revolutions in medicine in XVII-XIX centuries: disclaimer of
      Galenism and initiation of natural-scientific foundations of medicine. Report 5.
      The development of new conceptions about the structure and mechanisms of
      functioning of nervous system].
AB  - The article deals with the history of study of anatomy and physiology of central
      and peripheral nervous system in the course of scientific revolution in medicine.

PMID- 21899038
TI  - [The traditions of "the saint doctor" Gaas in Russian clinic: A.N. Kazem-Bek and
      V.A. Kazem-Bek (Kazan-Harbin)].
AB  - The article retrace the process of maintaining and passing on the humanistic
      traditions of Russian medicine founded by Doctor F.P. Gaas in the late XIXth -
      early XXth centuries. The biographies of Kazan physicians are presented,
      including eminent therapist professor A.N. Kazem-Bek (the representative of N.A.
      Vinogradov clinical school) from Kazan University and his son, Doctor V.A. Kazem
      Bek, who practised medicine in Harbin.

PMID- 21899039
TI  - [The traditional medicine in Transbaikalia].
AB  - The article covers the customs, the modes of treatment and safeguarding against
      diseases as integral components of Buryat traditional medicine.

PMID- 21899040
TI  - [The input of graduates of Russian military medical academies into fight against
      acute infectious diseases in pre-revolutionary Dagestan].
AB  - The population study permitted to establish the role of Russian military
      physicians in organization of medical business in Dagestan. The prevalence of
      acute epidemiologic diseases in pre-revolutionary Dagestan is examined. It is
      derived that mass propagation of infections was supported by cultural and
      economic backwardness, non-sanitary conditions in cities, lifestyle of mountain
      dwellers. The tradition to visit ill fellow villager resulted into mass morbidity
      and even in death collapse of entire population of mountain settlements (auls).
      The positive conditions to develop medical business developed after Dagestan
      joined Russia. The activities of Russian military physicians in the Caucasus
      coincided with the full swing of various infection epidemics among soldiers and
      residents. The measures undertaken by Russian military physicians permitted to
      liquidate the epidemics.

PMID- 21899041
TI  - [The museum of hygiene and its role in the cultural life of Russian society].
AB  - The considerable historical material was used to consider the issues of origin
      and development of museums of history in Russia. As an example the museum of
      hygiene of municipal medical prevention center of St. Petersburg was taken. The
      article proves the nowadays significance of such public institution as museum of
      hygiene. The role of prominent hygienists in the development of museum business
      in Russia is emphasized. For the first time the museum of hygiene is presented as
      one of institutions of preventive medicine of Russia.

PMID- 21899043
TI  - Synthesis of selenium-containing amino acid analogues and their biological study.
AB  - Synthesis of selenium-containing amino acid analogues is described. These
      compounds were prepared in a concise and short synthetic route in good yields by
      nucleophilic substitution reaction of pyridineselenol and quinolineselenol
      derivatives with N-phthaloylglycyl chloride followed by hydrazinolysis. The newly
      synthesized compounds were screened against different strains of bacteria and
      fungi.

PMID- 21899042
TI  - Towards a strategic plan: summary of APS strategic planning meeting. January 24
      25, 2011.

PMID- 21899044
TI  - [In vitro modeling of cell-scaffold interaction].
AB  - The simple approach for modeling of surface ligand - cell receptor interaction is
      proposed to control the effectiveness of peptide acceptor selected to be
      immobilized on a scaffold surface in order to promote specific cell adhesion and
      their subsequent proliferation and bone tissue formation. For experimental
      realization of such approach the affinity chromatography with use of macroporous
      monolithic sorbent is suggested. The biospecific GRGDSP-peptide performed the
      role of scaffold surface ligand which is responsible for cell adhesion, while the
      "cells" were simulated by polymer (polystyrene) micro particles with EDYPVDIYYLM
      DLSYSMKDD-peptide immobilized on their surface. The latter peptide is the
      integrin molecule active site which is responsible for RGD-sequence binding. Thus
      the ultra-short monolithic chromatography columns (CIM-disks) represent the
      simplified model of a scaffold possessing biospecific properties. The qualitative
      evaluation of complement interaction parameters was performed via frontal
      analysis method followed by adsorption isotherm plotting and subsequent
      linearization and mathematical treatment. The data obtained reliably indicate the
      highly specific character of biological pair binding. This was in a good
      accordance with results obtained in the cell culture experiments.

PMID- 21899045
TI  - [Conformational stability of serine proteinase inhibitor from the sea anemone
      Heteractis crispa].
AB  - The influence of different environmental values of the pH and temperature on the
      spatial organization of serine proteinase inhibitor from the sea anemone
      Heteractis crispa (=Radianthus macrodactylus) on the level of tertiary and
      secondary structure was studied by CD spectroscopy. The molecule InhVJ was shown
      to possess a high conformational thermo- and pH-stability. We determined the
      point of conformational thermotransition of polypeptide (70 degrees C) after
      which the molecule gets denaturational stable state with conservation of 80%
      proteinase inhibitory activity. The significant partial reversible changes of
      molecule spatial organization were established to occur at the level of tertiary
      structure in the process of acid-base titration in the range of pH 11.0-13.0.
      This can be explained by of ionization of tyrosine residues. The molecule InhVJ
      is conformationally stable at the low pH values (2.0). The quenching of tyrosine
      residues by acrylamide showed that two of these residues are accessible to the
      quencher in full, while the third part is available.

PMID- 21899046
TI  - [Mechanism of inhibitory effect of angiostatin on plasminogen activation by its
      physiologic activators].
AB  - The influence of angiostatin K1-4.5--a fragment of the heavy chain of plasmin and
      a powerful inhibitor of angiogenesis--on kinetic parameters (k(Pg) and K(Pg)) of
      human Glu-plasminogen activation under the action of urokinase (uPA) not having
      affinity for fibrin and fibrin-specific tissue plasminogen activator (tPA) was
      investigated. Angiostatin does not affect the k(Pg) value, but increases the
      value K(Pg) urokinase plasminogen activation. A decrease in the k(Pg) value and
      an increase in the K(Pg) value were found for fibrin-stimulated plasminogen
      activation by tPA with increasing concentrations of angiostatin. The obtained
      results show that angiostatin is competitive inhibitor of the uPA activator
      activity, while it inhibits the activator activity of tPA by mixed type. Such an
      influence ofangiostatin on the kinetic constants ofthe urokinase plasminogen
      activation suggests that angiostatin dose dependent manner replaces plasminogen
      in the binary enzyme-substrate complex uPA-Pg. In case of fibrin-stimulated
      plasminogen activation by tPA, both zymogen and tPA are bound to fibrin with
      formation of the effective triple tPA-Pg-fibrin complex. Angiostatin replaces
      plasminogen both from the fibrin surface and from the enzyme-substrate tPA-Pg
      complex that leads to a decrease in k(Pg) and an increase in K(Pg) of plasminogen
      activation. Inhibition constants by angioststin (Ki) of plasminogen-activator
      activities of uPA and tPA determined by Dixon method were found to be 0.59 +/-
      0.04 and 0.12 +/- 0.05 microM, respectively.

PMID- 21899047
TI  - [Isolation of expressed in E. coli human interferon beta1b (Ser17) by ion
      exchange chromatography].
AB  - A method for isolation of interferon beta1b (Serl7) from inclusion bodies,
      comprising the steps of solution and reduction of protein from the inclusion
      bodies, refolding, chromatography on DEAE-Sepharose, chromatography on SP
      Sepharose, concentrating, desalting and addition of stabilizers. The solution of
      reduced protein was diluted with pH 8.0 buffer of 50 mM Tris-HCl, 25 microM CuCl2
      and 0.5% Twin 20 for refolding. We used gradient of pH (from 9.3 upto 11.3) for
      elution of interferon-beta from cation-exchange column. We concentrated of eluate
      and then desalted on the Sephadex G-50 column with 1 mM NaOH. Then the protein
      solution was neutralized with mannitol and Na-phosphate. Obtained preparation of
      interferon-beta was pure by gel-electrophoresis and by HPLC analysis, and had
      practically indentical level of antiproliferative activity with well-known
      preparation of Betaferone. Thus we show the possibility of isolation and
      obtaining of pure and active interferone-beta by ion-exchange chromatography in
      the presence of non-ion detergent Twin 20. We believe this method for interferon
      betalb preparation is perspective for scaling and using in the develop of
      industrial technology for production of this preparation.

PMID- 21899048
TI  - [Human single chain antibodies directed to tumor necrosis factor].
AB  - Six unique phage antibodies to human TNF have been selected from a combinatorial
      library of human single chain fragment variable. ELISA and Western-blotting was
      used to study selected phage antibodies binding with TNF. The specificity of
      selected antibodies was determined by binding with interferon alpha and gamma,
      bovine serum albumin, ovalbumin and ubiquitin. Two antibodies, sA1 and sB3, were
      converted into a soluble single-chain antibody form and their affinity was 2.5
      and 13.7 nM respectively.

PMID- 21899049
TI  - [Monoclonal antibodies to type A, B, E and F botulinum neurotoxins].
AB  - Mouse monoclonal antibodies against the most acutely toxic substances, botulinum
      neurotoxins (BoNTs) of types A, B, E, and F, was generated and characterized,
      that recognize their respective toxins in natural toxin complex. Based on these
      antibodies, we developed sandwich-ELISA for quantitative detection of these
      toxins. For each respective toxin the detection limit of the assay was: BoNT/A -
      0.4 ng/ml, BoNT/B - 0.5 ng/ml; BoNT/E - 0.1 ng/ml; and for BoNT/F - 2.4 ng/ml.
      The developed assays permitted quantitative identification of the BoNTs in canned
      meat and vegetables. The BNTA-4.1 and BNTA-9.1 antibodies possessed neutralizing
      activity against natural complex of the botulinium toxin type A in vivo, both
      individually and in mixture, the mixture of the antibodies neutralized the higher
      dose of the toxin. The BNTA-4.1 antibody binds specifically the light chain (the
      chain with protease activity) of the toxin, whereas BNTA-9.1 interacts with the
      heavy chain. We believe that the BNTA-4.1 and BNTA-9.1 monoclonal antibodies are
      prospective candidates for development of humanized therapeutic antibodies for
      treatment of BoNT/A-caused botulism.

PMID- 21899050
TI  - [Preparation and characterization of monoclonal antibodies to Bacillus anthracis
      protective antigen].
AB  - Anthrax is the widespread acute infection disease, affecting animals and humans,
      refers to the bioterrorist threat agents of category A, because of the high
      resistance of Bacillus anthracis spores to adverse environmental factors and the
      ease of receiving them. We obtain a representative panel of 20 monoclonal
      antibodies against the key component of pathogenic exotoxins, anthrax protective
      antigen. Quantitative sandwich-ELISA for protective antigen with antibody
      obtained was developed. Six pairs of monoclonal antibodies showed the detection
      limit up to 1 ng/ml concentration of the protective antigen in blood serum.

PMID- 21899051
TI  - [Research properties of the exogenous recombinant human heat shock protein HSP70
      on test rodents].
AB  - Our research with Sprague-Dawley rats demonstrates protective properties of
      recombinant human heat shock protein 70 kDa (exogenous rhHSP70) as a prevent
      therapy agent for gram-positive sepsis. In this study we investigate acute
      toxicity of rhHSP70 on CD-1 mice and demonstrate very low dangerous of the
      substance.

PMID- 21899052
TI  - [Monoclonal antibodies labeled with colloidal gold for immunochromatographic
      express analysis of diphtheria toxin].
AB  - One-step rapid immunochromatographic method for detection of diphtheria toxin in
      different water samples (phosphate buffer, milk, human nasopharyngeal swab) with
      the conjugate of monoclonal antibodies labeled with colloidal gold was developed.
      The limit of visible detection of the diphtheria toxin is 10 ng/ml and 15 min
      time analysis. The use of silver sensitivity enhancement and scanning equipment
      decreased the detection limit to 1.25 ng/ml.

PMID- 21899053
TI  - [Molecular cloning and analysis of cDNA sequences encoding serine proteinase and
      Kunitz type inhibitor in venom gland of Vipera nikolskii viper].
AB  - Serine proteinases and Kunitz type inhibitors are widely represented in venoms of
      snakes from different genera. During the study of the venoms from snakes
      inhabiting Russia we have cloned cDNAs encoding new proteins belonging to these
      protein families. Thus, a new serine proteinase called nikobin was identified in
      the venom gland of Vipera nikolskii viper. By amino acid sequence deduced from
      the cDNA sequence, nikobin differs from serine proteinases identified in other
      snake species. Nikobin amino acid sequence contains 15 unique substitutions. This
      is the first serine proteinase of viper from Vipera genus for which a complete
      amino acid sequence established. The cDNA encoding Kunitz type inhibitor was also
      cloned. The deduced amino acid sequence of inhibitor is homologous to those of
      other proteins from that snakes of Vipera genus. However there are several
      unusual amino acid substitutions that might result in the change of biological
      activity of inhibitor.

PMID- 21899054
TI  - Cloning, molecular characterization and heterologous expression of a glutathione
      S-transferase gene in rice.
AB  - OsGSTL2 is one of three tandem-arranged glutathione S-transferase, lambda class
      genes in chromosome 3 of rice (Oryza sativa L.). It includes 9 introns and 10
      exons, and encodes a protein of 244 amino acid residues with a calculated
      molecular mass of 27.37 kDa. The predicted three-dimensional structure of OsGSTL2
      showed a typical glutathione S-transferase fold. Using semi-quantitative RT-PCR
      analysis, OsGSTL2 transcript was detected in the roots and leaves of seedling
      stage and tillering stage, and the roots, leaves and panicles of heading stage
      from rice plants, and the expression level of OsGSTL2 mRNA in rice roots show
      significant change under chlorsulfuron stress. The OsGSTL2 gene was cloned into
      pYTV vector and was transformed into yeast strain PEP4. Western blot analysis
      showed the exogenous OsGSTL2 was expressed in transformed yeast. GST activity of
      crude extracts of yeast showed the OsGSTL2 transgenic yeast had higher levels of
      GST activities than control yeasts. These findings suggested that the OsGSTL2 is
      a glutathione S-transferase and has potential use in detoxification.

PMID- 21899055
TI  - [Characterization of circulating RNA in plasma as potential tool for breast
      cancer diagnostics].
AB  - The representation patterns of 15 cytokines RNA in blood plasma and blood cells
      of patients with breast cancer and apparently healthy women were investigated.
      Relative levels of RNA IL-8 and IL-18 in plasma of breast cancer patients are
      significantly increased compared with control group. At the same time no obvious
      differences were found in relative concentrations of these transcripts in blood
      cells of patients and control groups. Relative concentration of IL-8 RNA was
      higher in blood plasma of locally advanced compared with early breast cancer
      patients.

PMID- 21899056
TI  - [Polysaccharide composition of mycelium and cell walls of the fungus Penicillium
      roqueforti].
AB  - Preliminary data on the polysaccharide composition of mycelium and cell walls of
      the submergedly grown fungus Penicillium roqueforti were obtained. Mild acid
      hydrolysis of mycelium and cell walls led to formation of glucose, mannose and
      galactose, whereas acid treatment under drastic conditions afforded glucosamine
      as the hydrolysis product of chitin, which content in the cell walls was
      estimated as 19%. Sequential treatment of the mycelium with hot water and 1 M
      NaOH at room temperature gave rise to several polysaccharide fractions, which
      were characterized by their monosaccharide composition. The main fraction
      obtained by the action of alkali, according to NMR spectroscopy, mass
      spectrometry and chemical methods of structural analysis data, is a linear alpha
      D-glucopyranan containing blocks of (1 --> 3)-linked glucose residues
      interconnected by (1 --> 4)-linkages. Water-soluble polysaccharides contained
      linear blocks of (1 --> 5)-linked beta-galactofuranose residues, probably
      connected with a mannan core. The data obtained may be important for
      chemotaxonomy of the genus Penicillium.

PMID- 21899057
TI  - [1,10-phenantroline europium complexes: their inclusion in liposomes and
      cytotoxicity].
AB  - For a series of 1,10-phenantroline tris-beta-diketonate europium complexes (EuC),
      cytotoxic activity on the HBL-100 human breast carcinoma cells was determined.
      Liposomal preparation of the most active EuC, V12, was also tested for
      cytotoxicity. Testing of this preparation in vivo on starting lethal murine model
      of T cell leukemic lymphoma ASF-LL showed that the inclusion of V12 in liposomes
      did not increase its antitumour activity in a local mode of administration.

PMID- 21899058
TI  - [Synthesis and antitumor activity of betulin, erythrodiol and uvaol aminopropoxy
      derivatives].
AB  - The synthesis of aminopropoxy derivatives of betulin, erythrodiol, uvaol and
      oleantriol via cyanoethylation of triterpenoids hydroxyl groups and subsequent
      reduction of cyanoethyl fragments is described. High and specific in vitro
      antitumor activity (cytotoxicity) of 3beta,28-di-O-[3-(aminopropoxy)]lupa-20(29)
      ene and 3beta-O-hydroxy-28-O-[3-(aminopropoxy)]olean-12-ene towards a wide range
      of human tumor cell lines is discovered. The aminopropoxy group is shown to be a
      new perspective pharmacophor group for design of anticancer agents on the basis
      of triterpenoids.

PMID- 21899059
TI  - [Coding region of far-red fluorescent protein katushka contains a strong donor
      splice site].
AB  - Computer analysis predicted a strong donor splice site within the 3'-part of the
      far-red fluorescent protein Katushka coding region. To test the functional
      activity of this site a model vector has been constructed. This vector encoded
      Katushka and green fluorescent protein TagGFP2 with a gene fragment of tafazzin
      in between. Normal splicing of this pre-mRNA should result in a frameshift
      between Katushka and TagGFP2. Alternatively, after splicing at internal katushka
      donor splice site appearance of Katushka-TagGFP2 fusion protein was expected.
      Expression of this construct in a mammalian cell culture led to bright red and
      green fluorescence. Therefore, katushka-specific donor splice site is functional.
      Disruption of this splice site by several silent substitutions resulted in red
      only fluorescent cells that corresponded to normal splicing. The mutant katushka
      can be used for visualization of pre-mRNA splicing at single cell level by
      fluorescence microscopy and flow cytometry.

PMID- 21899060
TI  - [3D-structure determination of fluorescent proteins by homology modeling combined
      with mass spectrometry].
AB  - A method for the 3D-structure generation of GFP-like fluorescent proteins is
      presented. The method is based on a combination of homology modeling for the
      overall spatial structure determination and mass spectrometry for the chromophore
      structure identification. The proposed approach can be applied to the spatial
      structure determination ofnoncrystalizable GFP homologs.

PMID- 21899061
TI  - [Receptor virus-cell interactions as an initial stage of infection].
AB  - The overview analyzes an update on and current concepts of the initial stage of
      viral infection of sensitive cells. It considers the nature of virus receptors,
      the mechanisms of virus-receptor interaction, methodical approaches to
      identifying the receptor role of cell molecules for various viruses, and the
      association of the initial stage of viral infection with its subsequent ones.

PMID- 21899062
TI  - [High-yield reassortant virus containing hemagglutinin and neuraminidase genes of
      pandemic influenza A/Moscowl/01/2009 (H1N1) virus].
AB  - The crossing of influenza A/Moscow/01/2009 (H1N1) virus and reassortant strain
      X31 (H3N2) containing the genes of internal and non-structural proteins of
      A/Puerto Rico/8/34 (H1N1) strain gave rise to reassortant virus ReM8. The
      reassortant contained hemagglutinin (HA) and neuraminidase (NA) genes of pandemic
      2009 influenza virus and 6 genes of high-yield A/Puerto Rico/8/34 (H1N1) strain.
      The reassortant ReM8 produced higher yields in the embryonated chicken eggs than
      the parent pandemic virus, as suggested by infectivity and HA activity titration
      as well as by ELISA and the measurement of HA protein content by scanning
      electrophoresis in polyacrylamide gel slabs. High immunogenicity of ReM8
      reassortant was demonstrated by immune protection studies in mice. The
      reassortant virus ReM8 is suitable as a candidate strain for the production of
      inactivated and subunit influenza vaccines.

PMID- 21899064
TI  - [Viral sorption on polyaniline, carbon nanotubes and their based nanocomposites].
AB  - The paper gives data on the sorption of influenza virus pandemic strain A/IIV
      Moscow/01/2009 (H1N1)swl, avian influenza viruses with A/H5 and A/H7
      hemagglutinin, poliomyelitis virus, and T4-D bacteriophage on polyaniline
      sorbents, carbon nanotubes, and their based nanocomposites. The sorption of
      viruses occurred in different solutions at 4-37 degrees C during 15 min or more.
      The rate of viral sorption depended on the structure of sorbents.

PMID- 21899063
TI  - [NP gene of pandemic H1N1 virus attenuates virulence of mouse-adapted human
      influenza virus].
AB  - The authors studied a possible role of the caspase cleavage motif located in the
      nucleoprotein (NP) of pandemic influenza virus H1N1 in the regulation of viral
      virulence properties. A reverse genetics method was used to obtain chimeric
      seasonal-like mouse-adapted influenza virus hvA/PE/8/34 (H1N10) carrying either
      the NP gene of wild type pandemic virus with incomplete caspase motif ETGC or
      mutated pandemic NP with natural caspase cleavage site of human type ETDG. The
      wild-type NP gene of the pandemic virus was found to poorly fit to the gene
      pattern of closely related seasonal-like hvA/PR/8/34 virus (H1N1) and did not
      rescue mature virus production whereas a mutated NP with human-type caspase
      cleavage site maintained gene fitness, giving rise to a chimeric virus. The
      generated chimeric virus hvA/PR/8/34 carrying the mutated pandemic NP
      successfully replicated in the murine lung, but was attenuated and did not reach
      the virulence level of seasonal-like mouse-adapted virus hvA/PR/8/34. The
      findings indicate that the NP caspase cleavage site plays a role in viral
      adaptation and viral virulence in mammals.

PMID- 21899065
TI  - [Impact of herpesvirus infections on the level of proinflammatory cytokines in
      premature neonatal infants].
AB  - The aim of this study was to estimate the frequency of HSV and/or CMV among the
      pathogens causing intrauterine infections (IUI) and to investigate their impact
      on the level of proinflammatory cytokines in premature neonatal infants.
      Examinations were performed in 3 neonatal groups: 1) premature neonates with
      clinical manifestations of IUI; 2) those without IUI; 3) full-term newborns. In
      group 1, viral (HSV and/or CMV) and bacterial infections were detectable with the
      same frequency. Quantitative analysis of plasma IL-6 and IL-8 levels and the
      induced production of these cytokines by blood cells in vitro showed that in
      Group 1 neonates, IL-6 and IL-8 concentrations were substantially higher and the
      induced production of these cytokines was lowerthan those in Group 3. The
      detection of HSV and/or CMV markers in premature newborn infants was attended by
      a statistically significant rise in plasma IL-6 levels; the identification of the
      opportunistic bacterial microflora correlated with the higher concentration of IL
      8. In Group 1, wiferon produced an immunomodulatory effect, by lowering IL-8
      concentrations to the level observed in Group 3.

PMID- 21899066
TI  - [Role of hepatitis A and E viruses in the development of autoimmune diseases].
AB  - The mechanisms of development of autoimmune diseases may be associated with a
      complex of genetic, immune, hormonal, and infectious factors. Autoimmune diseases
      include a wide range of systemic and organ-specific diseases, including
      autoimmune hepatitis (AIH). It is currently assumed that the pathogenesis of AIH
      is due to compromised immune regulation in the presence of an exogenous
      triggering factor. Exogenous factors, such as viruses, may be triggers of AIH.
      There may be different ways of initiating an autoimmune response by viruses,
      which includes nonspecific T-lymphocyte activation and molecular mimicry. There
      is much evidence supporting the initiating role of hepatitis viruses in the
      development of AIH and other autoimmune diseases. The development of AIH symptoms
      during hepatitis A and E virus infections has been described elsewhere. The
      creation of animal models of viral hepatitis is required to confirm the
      hypothesis that the viruses trigger the development of AIH and other autoimmune
      manifestations.

PMID- 21899067
TI  - [Comparative evaluation of Leningrad-3 mumps vaccine virus neurovirulence in a
      neonatal rat model].
AB  - The neurovirulence and replication potential of several mumps virus strains,
      including Leningrad-3 mumps vaccine virus (FSUE SIC "Microgen", Russia) and wild
      type strains isolated in the Novosibirsk Region (Russia), were assessed in rat
      tests. The mean neurovirulence scores of the Leningrad-3 virus (< 4.0) were
      significantly lower than those of wild type strains (ranging from 6.1 to 15.2)
      and were in accordance with the scores determined for other attenuated mumps
      vaccine strains (usually ranging from 0 to 5). In general, the relative ability
      of the viruses to replicate in the rat brain tracked with their neurovirulence
      scores. These results indicate a low neurovirulence potential of the Leningrad-3
      mumps vaccine virus for humans.

PMID- 21899068
TI  - [Use of RT-PCR and enzyme immunoassays for the specific diagnosis of Crimean
      hemorrhagic fever].
AB  - The objective of the investigation was to evaluate the efficiency of the RT-PCR
      kit "AmplySens CHF" produced by InterlabService of the Central Research Institute
      of Epidemiology and that of the ELISA kits made by the D. I. Ivanovsky Research
      Institute of Virology for the specific diagnosis of Crimean hemorrhagic fever
      (CHF). Examination of sera from CHF patients from the Astrakhan Region showed
      that positive RT-PCR results were observed in 95.2 and 37.5% on days 4-8 and 9-13
      after disease onset, respectively; but they were absent on days 13-17. Positive
      ELISA-IgM results were found in 93% on disease days 6 to 16. A high percentage
      (78.9%) of positive IgG samples was seen only on days 9-16. Thus, RT-PCR has a
      marked efficiency in diagnosing CHF until day 8 of illness while ELISA-IgM has it
      on day 8 or later. ELISA-IgG can be considered to be a confirming rather than
      compulsory test. The findings suggest that the RT-PCR kit "AmplySens CHF"
      produced by InterlabService of the Central Research Institute of Epidemiology and
      that of the ELISA kits made by the D. I. Ivanovsky Research Institute of Virology
      have a pronounced sensitivity and specificity and a high efficiency when
      concurrently used to verify CHF in patients.

PMID- 21899069
TI  - [Antigenic diversity of African swine fever viruses].
AB  - Data on the seroimmunotypic and hemadsorbing characteristics of African swine
      fever virus (ASF) are summarized. According to the results of immunological
      sampling in pigs and those of hemagglutination inhibition test, the known ASFV
      strains and isolates were divided into 11 groups, 8 were characterized as
      seroimmunogroups having their specific reference strains. A 110-140-kD ASFV
      serotype-specific nonstructural major glycoprotein was identified. It is
      suggested that it is the glycoprotein that corresponds to the genetic engineering
      detected virus-specific homolog of lymphocyte membrane protein CD2, gene deletion
      of which results in the loss of hemadsorbing properties by ASFV.

PMID- 21899070
TI  - [Comparative characteristics of the biological properties of small ruminant
      lentiviruses].
AB  - The infections caused by small ruminant lentiviruses include diseases, such as
      Maedi-Visna (MV) and caprine arthritis-encephalitis (CAE). According to
      phylogenetic findings and their common origination, small ruminant lentiviruses
      were divided into Groups A, B, C, D, and E. Cultivation of the lentiviruses
      displayed the cytopathic effect of the CAE virus strain 75 G-63 in the primary
      culture of goatling synovial membrane cells, which was shown by monolayer
      destruction and polynuclear cell formation; this was uncharacteristic for M-88, K
      796, and Tverskoy strains. A high homology was found for the Tverskoy strain with
      Group B small ruminant lentiviruses and the M-88 and K-796 strains with their
      Group A.

PMID- 21899071
TI  - [Efficiency of coadministration of immunomodulators and vaccine in an experiment
      on tick-borne encephalitis].
AB  - Experiments on a tick-borne encephalitis (TBE) model in CBA and BALB/c mice
      demonstrated that immunomodulators (ridostin, polyribonate, and peptidoglycan
      160) and a specific vaccine against TBE were significantly effective in
      increasing the level of a protective effect and life expectancy in the
      experimental group as compared to the control group. The findings allow one to
      recommend the immunomodulator ridostin in combination with the inactivated
      vaccine for the emergency prophylaxis of TBE in its virus-infected subjects in
      the foci of infection.

PMID- 21899072
TI  - [Sanitary service of West Special Military District on the eve and in the first
      days of the Great Patriotic War of 1941-1945].
AB  - This article evaluates military and political situation in the world and
      operational-strategic environment on the West Theater of operations on the eve of
      the Great Patriotic War (1941-1945). We analyze structure and overall condition
      of sanitary service of West Special Military District of the Workers and Peasants
      Red Army and causes of failure of mobilization, organization and deployment of
      military units and establishments from the beginning of aggression of Fascist
      Germany to the Soviet Union.

PMID- 21899073
TI  - [Problems of hygiene of children and adolescents in the military health care].
AB  - The article presents the current issues hygiene mechanical prevention of disease
      in the younger generation in re-formation of the Russian Armed Forces, the
      economy, health, education and ecological trouble.

PMID- 21899074
TI  - [About the microbiological criteria for air quality barracks in the far north].
AB  - A comparative study of air quality in terms of microbiological indicators in the
      barracks room personnel a number of units of the Northern Fleet is perfomed. The
      direct dependence of the degree of microbial contamination of air and the
      frequency of respimratory diseases from the specific volume of space per person
      is showed. Criteria for assessing air quality in terms of microbiological
      indicators and a set of measures to improve it are suggested.

PMID- 21899075
TI  - [First experience of laparoscopic appendectomy in the 150-bed garrison hospital].
AB  - The article reflects the results of the first laparoscopic appendectomy
      experiment which was conducted on the base of 30 person department of the
      military hospital for 150 patients. The researcher made the statistical analysis
      of the results of acute appendicitis diagnostic and cure among young men. For the
      group of patients whit catarrhal form of acute appendicitis separate analysis was
      committed. It was found out that in the half of cases the clinic and laboratory
      scheme of acute appendicitis does not differ from the destructive one. These
      results made the researcher comprehend the necessity of additional ways of
      diagnostic in the acute appendicitis shady cases. It is also necessary to develop
      a medicinal and diagnostic algorithm for shady appendicitis in accordance with
      diagnostic conditions of military hospital for 150 patients.

PMID- 21899076
TI  - [Results endodissection of perforating leg ulcers in the treatment of trophic
      ulcers of venous etiology].
AB  - This article analyzes the results of endoscopic dissection of perforating veins
      in the calf against trophic disorders in 106 patients. All the patients were
      performed endodissection perforating veins in combination with phlebectomy
      (remove any large or small subcutaneous Vienna throughout). Catamnesis in these
      patients was about 8 years.

PMID- 21899077
TI  - [The system of rehabilitation of specific functions of the female body of
      patients with benign ovarian neoplasm after urgent operations].
AB  - The authors have developed a system of medical rehabilitation of specific
      functions of the body of troops of women with benign ovarian neoplasm after
      urgent operations. As a result, the frequency of inflammatory complications was
      reduced to 4.8%, menstrual function was restored in 9.6-14.5% of cases, endocrine
      -in 9.1-14.5%, sexual--in 7.8-17.4%, reproduction--in 37.5%, to ensure good
      quality of life--in 74.6-92.3% cases.

PMID- 21899078
TI  - [Scheme of the diagnostic of secondary cognitive impairment in outpatient].
AB  - Cognitive disorders developing as consequence of a number of diseases of brain,
      are an actual problem. Now diagnostics techniques of cognitive disorders have not
      entered yet into wide and daily medical practice. Thus timely and exact
      diagnostics of these conditions allows to begin therapy in the earliest term. The
      offered three-level diagnostic algorithm of research will help to organise early
      diagnostics of cognitive disorders at the minimum expenditures of labour that
      will be reflected in quality of rendering of medical aid and can lead to decrease
      in direct and indirect expenses on treatment and rehabilitation.

PMID- 21899079
TI  - [Clinico-instrumental characteristics of arterial hypertension, liable to the
      ishemic stroke].
AB  - Clinico-instrumental characteristics of arterial hypertension, liable to the
      ishemic stroke were studied. The pecularities of clinical, neurological picture
      of disease and results of instrumental methods of examination were determined.
      These peculiarities let to educe the course of arterial hypertension, liable to
      the ishemic stroke. This course appeared because of hypertensional
      macroangiopathy during 3-5 years, two atherosclerotic stenosis of brachiocephalic
      arteria, occlusions and stenosis of these arterias, left ventricular hypertrophy
      of hypodynamic type, circulatory dynamics against the bad daily profile of
      arterial pressure and/or increased variability of arterial pressure accompanied
      with ischemic attacks, signs of chronicle heart failure and circulatory
      encephalopathy. The scheme of the examination of patients with AH during the long
      term examination with the goal of prophylaxis IS was offered.

PMID- 21899080
TI  - [Servicemen mental health monitoring in different stages of military service].
AB  - The effectiveness of psychoprophylactic work on each of military service basic
      stages and how to optimize it have been presented. The universal system of mental
      health monitoring in whole period of military service has been developed. A
      possibility of differentiated rapid assessment of mental status for effective
      monitoring of mental health has been analyzed. Some practical recommendations for
      the unit doctors in the principles of servicemen distribution by group of mental
      health level and taking the appropriate organizational decisions have been
      advised.

PMID- 21899081
TI  - [Preparation of the flight crew to bailout].
AB  - The authors demonstrate that the training of flight personnel to the ejection
      from an aircraft in distress is a learning system that includes interconnected
      types of land-based activities: studying the material part of the means of
      salvation, documentation, regulatory need for ejection and the ejection rule;
      exercises in the cockpit; training on special simulators; parachute training;
      demonstration bailout; making available to the flight crew documents the forced
      ejection of the Air Force to analyze their outcomes.

PMID- 21899082
TI  - [Appliancation of logistics in resources management of medical asset].
AB  - The usage of basic regulations of logistics in practical activity for providing
      joints and military units with medical asset is theoretically justified. The role
      of logistics in organizing, building and functioning of military (armed forces)
      medical supply system is found out. The methods of solving urgent problems of
      improvement the resources management of medical asset on the basis of logistics
      are presented.

PMID- 21899083
TI  - [1602th district military hospital--70 years].
AB  - An important role in medical care of troops (forces) of the North Caucasian
      military district, and most recently--the Southern Military District under
      martial of action and crisis situations, as well as in peacetime, performs 1602th
      District Military Hospital of Defense Ministry of Russia. Hospital team has
      achieved significant results in treatment and diagnostic work, and became a
      leading military medical institution in the North Caucasus and the Southern
      Federal District. Today the hospital is not only a medical-diagnostic, but a
      methodical, scientific, educational and teaching center in the county. He has
      good material and technical basis and equipped with modern medical equipment. The
      article described the historical path of the hospital and its current status.

PMID- 21899084
TI  - [Participation of the Moscow Sisters of Mercy of the Russian-Japanese War of 1904
      1905].
AB  - The article considers the role of the Moscow community of Sisters of Charity
      palladium in the Russian-Japanese War of 1904-1905. Thanks to the nurse caring
      for the wounded was sufficiently qualified and in medical facilities to maintain
      cleanliness and order. As a result, despite the adverse conditions are manual and
      errors, it was possible not only to preserve life and health of the wounded, but
      also to protect soldiers from epidemic diseases. Thus, the bridge-bank community
      of the Sisters of Charity has made a positive contribution to the combat
      capability of serving in the Far East of the Russian army.

PMID- 21899085
TI  - [Strategy for the development of dipeptide drugs].
AB  - The author describes an original approach to the development of dipeptide drugs
      based on the concept of the leading role of the beta-bend in the interaction of
      biologically active endogenous peptides with their receptors. The approach called
      "peptide-based drug design" includes both developments from the structure of a
      known psychotropic agent toward its topological peptide analog and developments
      from the active dipeptide site of a neuropeptide toward its mimetic. This
      strategy has been worked out at the V.V. Zakusov Research Institute of
      Pharmacology for 25 years. Results of investigations that discovered endogenous
      peptide prototypes of the known non-peptidic drugs (piracetam and sulpiride) are
      presented. They provided a basis for the creation of highly active non-toxic oral
      dipeptide preparations, such as nootrop Noopept, potential anti psychotic Dilept,
      and potential selective anxiolytic GB-115.

PMID- 21899086
TI  - [The phylogenetic position of Chlamydia strains isolated from monkeys and humans
      with Chlamydial pathology in the family Chiamydiaceae. Genotypic and phenotypic
      properties of this pathogen].
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 GenBank
      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 non-plasmid 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 and
      development cycle disorder and decrease of Chlamydia virulence can be related to
      probable changes in the nucleotide sequence of the gene under consideration.

PMID- 21899087
TI  - [Tissue equivalent for the closure of extended urethral defects].
AB  - The aim of the present work was to develop a method for culturing epidermal
      keratinocytes to be used in a tissue equivalent for the closure of extended
      urethral defects. The experiment was carried out using 15 rabbits. Skin biopsies
      were obtained from the inner surface of the ear. The tissue equivalent consisted
      of collagen gel with embedded fibroblasts and epidermal keratinocytes grown on
      its surface; lavsan-mesh endoprosthesis served as the framework. Prefabrication
      of the neourethral plate was performed on the superficial fascia of m. rectus
      abdominis. The neourethral tube was formed after engraftment which was complete
      in all 15 animals. A histological study revealed morphological similarity of the
      neourethral tube thus engineered and the normal urethra.

PMID- 21899088
TI  - [Improvement of the organization of oncological aid under conditions of specific
      technogenic load on the population].
AB  - Social and economic disbenifits due to mortality from malignant neoplasms were
      estimated taking into account the losses of man-years of work, mean life
      expectancy for the sick, losses from temporary disablement and invalidization
      caused by malignancies, and the cost of oncological aid. The study was based at
      an area in Uzbekistan subjected to pollution by industrial wastes from an uranium
      extracting enterprise. A special purpose-oriented program has been elaborated for
      the correction of oncological aid currently provided to the workers of the Navoi
      mining and metallurgical works and the local population. Its implementation
      resulted in a 13% reduction of standardized mortality from malignant neoplasm in
      2004 compared with 1999 and another 24% in 2009. The disbenefit prevented by the
      reduction of mortality at active ages is estimated at 60,6 mln rubles.

PMID- 21899089
TI  - [H1N1V influenza epidemic of 2009 in Russia].
AB  - The paper describes dynamics, distribution and morbidity rate during the 2009
      A(H1N1)v influenza epidemic in Russia. The epidemic appears to have been
      especially severe in the cities of the Far-East and Siberian Federal Districts
      where the average morbidity rate ranged from 6.4% to 19.2% (mean 10.3%) and the
      epidemic duration from 7.8 to 8 weeks. In less affected Southern and Central
      Federal Districts A(H1N1)v influenza occurred in 5.7% of the population.
      Schoolchildren aged 7-4 years showed the highest morbidity rate of 28.8%. The age
      group of 18-53 years accounted for 79.4% of the total lethality. Viral isolates
      were genetically stable and exhibited 98.9% hemagglutnin (HA) homology with
      reference viruses. None of the strains had an amino acid substitution at position
      275 of neuraminidase (NA) responsible for resistance to oseltamivir. Towards the
      end of the epidemic, the viral population displayed a significant rise in the
      number of strains containing mutations in 4 genes (4 HA, 2 NA, 2 PB2 and 1 PA
      mutations respectively). 26.7% of the viral isolates obtained in the end of the
      epidemic had D222G substitution responsible for tropism of viruses to lung
      tissues. Epidemiologically, the 2009 A(H1NI)v influenza epidemic is described as
      moderate based on the absence of pathogenicity determinants typical of both
      A(H1N1) influenza virus of 1918 and A(H5N1) virus. The paper compares the 2009
      epidemic with those caused by A/Honkong/68 and A/USSR/ 90/77 viruses. The
      necessity of classification for the discrimination between A(H1N1) subtype
      viruses is emphasized.

PMID- 21899090
TI  - [The absence of tolerance and withdrawal syndrome after the treatment with the
      new L-tryptophane-containing dipeptide anxiolytic GB-115].
AB  - Effects of GB-115, an anxiolytic L-triptophan-containing dipeptide, based on the
      endogenous tetrapeptide cholecystokinin, were evaluated during and after
      withdrawal of its long-term administration to rats in comparison with diazepam.
      It was shown using the "elevated plus-maze" test (EPM) that GB-115 retained its
      anxiolytic properties after i/p injections at a daily dose of 0.1 mg/kg fo r 30
      days. Discontinuation of dipeptide administration 24h and 48 hours after the
      onset of the experiment did not lead to behavioral (increased anxiety,
      aggression) and convulsive (decreased corazol sensitivity) manifestations of
      withdrawal syndrome. In contrast, the withdrawal ofdiazepam (4.0 mg/kg/day, ip,
      30 days) induced the anxiogenic response in EPM, reduction of the aggression
      threshold, and enhancement of convulsive readiness. Significant differences
      between GB-115 and diazepam effects on the levels of dopamine, norepinephrine,
      and their metabolites after chronic administration and withdrawal were restricted
      to striatum.

PMID- 21899091
TI  - [Association between changes in characteristics of local cerebral blood flow and
      slow brain electrical activity in patients with dyscirculatory encephalopathy].
AB  - Associated changes in the characteristics of local cerebral blood flow (CBF) and
      slow brain electrical activity were studied in 40 patients with dyscirculatory
      encephalopathy. CBF and CBV (cerebral blood volume) values for the frontal and
      temporal cortex and basal ganglia positively correlated with the constant
      potential values in the central lead influenced by the blood flow rate in the
      upper sagittal sinus.

PMID- 21899092
TI  - [The search for a sensor of intracellular sodium involved in pathogenesis of
      hypertensive disease].
AB  - Na+,K+ ATPase plays the key role in regulation of intracellular concentration of
      monovalent cations and related functions essential for electrogenesis and the
      maintenance of cell volume. This review is focused on the new data showing that a
      long-term increase of the intracellular Na+ level induces expression of early
      response genes and genes involved in regulation of apoptosis. Results of the
      studies of the Na+ sensor and its role in pathogenesis of the salt-sensitive form
      of hypertensive disease are summarized.

PMID- 21899093
TI  - [Mechanisms of hypermetabolic states].
AB  - Current concepts of mechanisms of hypermetabolic states in the body and its
      selected organs are discussed. Special attention is given to hepatic processes
      and changes of energy metabolism in hypermetabolic hepatocytes. It is shown that
      hypermetabolic cells have properties characteristic of the metabolism stimulation
      phase in cells showing a non-specific reaction to an injury. Differences between
      cellular hypermetabolism and stimulated metabolism in an injured cell are
      considered. It is hypothesized that hypermetabolism at the cellular level may be
      regarded as a stably prolonged phase of stimulated metabolism related to the cell
      non-specific reaction to an injury.

PMID- 21899094
TI  - [Radioecological approaches to ranking radiation dangerous objects].
AB  - The paper gives complex criteria for evaluating the hazard of radiation dangerous
      objects (RDO). The proposed criteria include the following indicators: the ratio
      of the cumulative activity of radioactive waste to a hazard factor (D value) or
      to the allowable level of i-radionuclide in the storage; the power of an
      effective gamma-radiation dose; the rate of radionuclide migration; the doses of
      human radiation. A scoring system for the hazard of RDO from the above indicators
      is given.

PMID- 21899095
TI  - [Influence of geliophysical factors on neonatal morbidity in the Belgorod
      Region].
AB  - The study of the influence of geliophysical factors on neonatal morbidity in the
      Belgorod Region in 2000 to 2008 established a rise in the rate of congenital
      malformations, fetal hypoxia and asphyxia, prematurity, and overall neonatal
      morbidity during a period of high solar activity.

PMID- 21899096
TI  - [The specific features of microbiocenoses in children living under conditions of
      anthropogenic pressing].
AB  - The specific features of enteric and nasopharyngeal microbiocenoses and the
      species composition of bifidobacteria have been studied in children living in the
      industrial towns of the Irkutsk Region under the existing anthropogenic load.
      Ambient air pollution is characterized and a presumptive human health risk
      assessed.

PMID- 21899097
TI  - [The blood levels of stable toxic substances in the native residents of costal
      Chukotka and their children's infection morbidity].
AB  - A considerable reduction in the blood levels of stable organic pollutants (SOP)
      has been noted in the mothers of native ethnicities of costal Chukotka during a 5
      year period, which may be accounted for by certain purification of food chains,
      altered diet with emphasis on delivered products, and long-term breastfeeding.
      The elevated level of SOP in children from birth to age 5 years is explained by
      long-term breastfeeding and the early consumption of local foods. The content of
      heavy metals (mercury and lead) in both maternal and children's blood has
      unchanged for 5 years. The children's infection morbidity has been quite high; at
      the same time no associations of the children's blood levels of toxic substances
      with the incidence of infectious diseases have been found. However, two children
      maximally exposed to SOP and metals have been observed to be rarely susceptible
      to diseases.

PMID- 21899098
TI  - [Helicobacter pylori: routes of transmission of infection (a review of
      literature)].
AB  - The paper reviews the data characterizing the routes of transmission of
      Helicobacter pylori. Particular emphasis is laid on the water transmission route
      that has not been long considered to be important despite strong epidemiological
      evidence that allows it to be regarded as one of the most important routes of
      transmission of this infection. It describes the most favorable conditions for
      this microorganism to survive in the water systems, including plumbing, and a
      possible survival mechanism via biofilm formation and zooplankton symbiosis. The
      pathogen is able to bind to autochronous microorganisms in the biofilms and to
      generate itself the latter. It is not inconceivable that this microbe can persist
      and even multiply within protozoa. Due to the improved analytical studies, there
      are additional possibilities to detect new pathogenic microorganisms that have
      not been historically regarded as pollutants. These microorganisms are of
      interest to community hygiene specialists. The preferred routes of urban and
      rural transmission of the pathogen may be different, which should be taken into
      account when elaborating preventive measures.

PMID- 21899099
TI  - [Hygienic evaluation of direct heating of the air delivered to the shaft].
AB  - The paper gives the results of exploring a test pre-heating system for the air
      (APHS) delivered to the shaft. The system has been first used in the Urals. The
      supply air is heated by burning natural gas in the air current. The APHS system
      with a RG air heater (000 "Gas-Engineering") is equipped in addition to the
      existing heaters to enhance heat supply reliability in northern conditions. The
      data of the studies show that in all periods of the heating season (interseason,
      moderate frosts, the coldest month), the concentrations of hazardous substances,
      such as nitric oxides, nitric dioxide, sulfur dioxide, carbon dioxide,
      benz(a)pyrene, solid aerosol in the shaft-delivered air, do not exceed those
      given in the existing regulation provided that the design operating conditions
      are met. With the maximum gas consumption, the coldest month only was marked by
      the nitric dioxide content being greater than the standard values, causing the
      maximum projected natural gas consumption to be lower in the APHS system. The air
      level of nitric dioxide proved to be a major hygiene indicator while using this
      air heater.

PMID- 21899100
TI  - [Characteristics of industrial noise at the Astrakhan gas processing plant].
AB  - The level and nature of air pollution were studied in various objects of the
      Astrakhan gas processing plant. The necessity of introducing technical-hygienic,
      organizational, and medical measures to reduce the adverse effect of the noise on
      workers is warranted.

PMID- 21899101
TI  - [Occupational morbidity among health care personnel in the Primorsky territory].
AB  - Occupational morbidity rates in health care personnel have recently attracted the
      particular attention of the specialists of the Russian Inspectorate for the
      Protection of Consumer Rights and Human Welfare and occupational pathologists.
      The rise in the incidence occupational diseases (during nosocomial infection) in
      the medical workers of therapeutic-and-prophylactic institutions affects the
      reduction of their ability to work. Contact with blood or other biological fluids
      and with bacteria-excreting patients, handing medical waste, and influence of
      work environment factors are causes of nosocomial infection among the medical
      staff.

PMID- 21899102
TI  - [Biological age as an integral indicator of the impact of working conditions on
      workers' health].
AB  - The integral health indices (biological age, age-related individual physiological
      features during a long-term (during a shift) contact with occupational allergens
      and working factors, the body's wear rates, and functional adaptive processes
      under hazardous working conditions) were studied in workers having dangerous
      jobs.

PMID- 21899103
TI  - [Scientific-and-methodic bases of adolescents' health protection and promotion in
      Russia].
AB  - The problems that have a considerable impact on health in population groups of
      all ages but on that of adolescents in particular, have been formed during the
      complex and unstable situation in Russia and with high morbidity rates among the
      children, adolescents, and young people. Power bodies, concerned ministries,
      agencies, and nongovernmental organizations show no consistency of actions in
      elaborating and implementing programs and measures to prevent and correct
      adolescents' health and developmental disorders. The foregoing suggests that the
      "dolescents' Health and Development in Russia" strategy that considers Russian
      and international experience with the rising generation's health care is urgent.
      The paper presents basic principles, study areas, and indicators of the expected
      efficiency of the complex activities of ministries, agencies, governmental and
      public organizations, medical and pedagogical communities for ensuring normal
      development and health promotion for the adolescents.

PMID- 21899104
TI  - [Morbidity rates in university students].
AB  - The current higher education modernization is accompanied by the intensification
      of an educational process. Due to intensive mental work and a need to adapt to
      new educational conditions, the students belong to a group of increased risk.
      Morbidity rates were studied in medical students during education. The study
      indicated a rise in morbidity in the period 2005 to 2009, high morbidity rates in
      first- and second-year students, the seasonal pattern of diseases, and a
      preponderance of respiratory diseases and mental disorders as a ground for a
      sabbatical leave, which is due to the specific features of education at a medical
      higher educational establishment.

PMID- 21899105
TI  - [Heart rhythm variability during neuro-psychological stress].
AB  - The paper gives the results of studying heart rhythm variability in medical
      students during their study at a higher educational establishment with regard to
      the typological features of the autonomic nervous system. Significant diferences
      have been found in both the temporal and spectral parameters of heart rhythm in
      relation to the dominance of the autonomic nervous system and the time of their
      studies. Analysis of heart rhythm variability could estimate the total activity
      of regulatory mechanisms and the ratio between the sympathetic and
      parasympathetic autonomic nervous systems in the students during their study.

PMID- 21899106
TI  - [Somatotypological characteristics of the development of fat component in
      students].
AB  - Individual typological characteristics were studied in first- and fourth-year
      female students. It was shown that the dominant somatotype was micromesomatic in
      the first-year students and macrosomal in the senior students. Body component
      composition was studied in the examinees. No significant average group
      differences were found in the absolute and relative body fat content in the
      students. The somatotype distribution using the weight-height ratio indicated
      significant differences in fat components in the female representatives of
      different types of constitution.

PMID- 21899107
TI  - [Gender approach to studying reproductive aims in young people].
AB  - The paper presents the preliminary results of estimating reproductive potential
      in young people. Gender characteristics have been revealed in the sexual behavior
      (the young men start a sexual life at significantly earlier age; different
      attitudes towards contraception) and reproductive aims (children rank fourth
      among family values; a low proportion of persons who wish to have two children or
      more) of the youth in the Republic of Tatarstan. Certain risk factors influencing
      reproductive health impairments are identified. Differential forms of
      prophylactic work, which are aimed at promoting reproductive health for young
      people, are proposed.

PMID- 21899108
TI  - [Rationale for hygienic regulations for the use of a new mixed herbicide
      antidote].
AB  - The paper deals with the investigation of a new chloroquinoline derivative
      antidote and with the substantiation of hygienic standards and regulations for
      the safe use of its based mixed drug, by applying a procedure for assessing risks
      for workers and the population. According to the results of the studies
      conducted, the authors have established the hazard of the new chloroquinoline
      derivative antidote, developed respective hygienic standards, and provided a
      scientific rationale for the hygienic regulations for the safe use of the mixed
      herbicide, which prevent the negative impact of its residues in the foodstuffs
      and environmental objects on workers and the population.

PMID- 21899109
TI  - [Determination of ammonia in ambient air by ion chromatography].
AB  - The use of the well-known methods for testing the content of ammonia in the air
      of a populated area at the average daily maximum allowable concentration (0.04
      mg/m3) is associated with the high requirement for chemical reagents and with
      considerable time. Deionized water proposed to be used as an absorption solution
      in the sample collector with the final ion chromatographic determination of
      ammonia is an alternative to solving the problem and enables air ammonia to be
      determined with a sensitivity of 0.02 mg/dm3.

PMID- 21899110
TI  - [Contribution of professor L.A. Syrkin to the development of methodical bases for
      anthropometric studies in children and adolescents].
AB  - The paper historically considers the impact of social differentiation on the
      physical development of children and adolescents. It analyzes the scientific
      contribution of Prof. Lev Abramovich Syrkin (1894-1951) to the formation and
      development of a system for anthropometric studies in Russia in the first half of
      the twentieth century (1920s to 1950s), to the elaboration of principles in the
      standardization of tools, and to the unification of anthropometric studies and
      standards for the physical development of preschool and school children.

PMID- 21899111
TI  - [All-Russian hygienic exhibitions and museums].
AB  - The material about the popularization of hygiene and health education in Russia
      in the second half of the 19th century to early 20th century through exhibition
      and museum activities has been collected for the first time and analyzed in the
      paper. The role of scientists and scientific medical societies in this process is
      noted. The significance of museum and exhibition activities in this area for the
      development of medical science is defined.

PMID- 21899112
TI  - [The utilization of omegalicin in treatment of psoriasis].
AB  - The correcting action of omegalicin against the background of conventional
      treatment of psoriasis was investigated. It is established that omegalicin
      moderately increases the generation of active forms of oxygen needed to suppress
      the processes of proliferation at the expense of changing the activity of
      catalase, superoxide dismutase and glutathione peroxidase.

PMID- 21899113
TI  - [The determination of content of circulating CD32+CD40+ micro particles: the
      modification of method of assessment of destruction of endothelial cells].
AB  - The purpose of study was to develop and test the method of determination of
      destruction of endotheliocytes in blood-vascular system. The level of circulating
      endothelial cells was determined by enumeration of CD32+CD40+ micro particles by
      means of flow cytofluorometry. During the application of the modified method it
      is demonstrated that in patients with metabolic syndrome the amount of CD32+CD40+
      micro particles is twice higher than in the control group (p < 0.05). The
      research data revealed the increase of content of big endothelin and atherogenic
      lipoproteids. The method of determination of the level of circulating CD32+CD40+
      micro particles can be applied to assess the desquamationed endotheliocytes.

PMID- 21899114
TI  - [The levels of enzymes of blood neutrophilic leukocytes during the impact on the
      organism of vibration, vibration in aggregate with nickelous dust and nickel
      hydroaerosol].
AB  - The predominant impact of vibration and vibration in aggregate with nickelous
      dust and nickel hydroaerosol on the organism of workers administer significant
      influence on the levels of blood neutrophilic leukocytes and such neutrophil
      enzymes as acid and alkaline phosphatase and myeloperoxidase. In addition to that
      the activity of acid and alkaline phosphatases increases and the activity of
      myelopemroxidase reliably decreases. The intensive alteration of enzymes'
      activity develops already on the preclinical stage and even worsens in patients
      with vibratory disease. At the contact with the higher levels of nickel
      hydroaerosol the alteration of activity of these enzymes develops in early period
      at the experience less than 10 years.

PMID- 21899115
TI  - [The characteristics of iron metabolism under iron-deficiency anemia and chronic
      disorders anemia].
AB  - The study investigated the issues of iron metabolism under iron-deficiency anemia
      and chronic disorders anemia and dependencies of production of IL-1? and sICAM-1
      immunoinflammatory markers from degree of severity and duration of anemia. The
      study data indicates that under iron-deficiency anemia lactoferrin and sICAM-1
      are the negative regulators of hemopoiesis. The inhibition of transferrin
      expression by the proinflammatory cytokines is one of the causes of inefficient
      hemopoiesis under chronic disorders anemia.

PMID- 21899116
TI  - [The conditions of arrangement of the thrombin generation test to detect the
      hypercoagulation status].
AB  - The study covered the impact of modes of preparation of plasma samples to arrange
      the thrombin generation test for the purpose to establish adequately the
      hypercoagulation status. The optimal regimen is determined to prepare the samples
      to be used in the study. The group of females was involved into the study to take
      the composite oral contraceptives to demonstrate the possibility to apply the
      thrombin generation test to reveal the hypercoagulation.

PMID- 21899117
TI  - [The implementation of polymerase chain reaction technique: the real time to
      reveal and differentiate the viruses of human papilloma of high carcinogenic
      risk].
AB  - The polymerase chain reaction technique was applied in "real time" format to
      evaluate the occurrence rate and infection ratio of various genotypes of human
      papilloma of high carcinogenic risk in virus-positive women and contact persons.
      The examination sampling consisted of 738 women aged of 17-50 years. The
      examination results permitted to establish high percentage of infection of 546
      patients (74%) by carcinogenic papilloma viruses. The analysis of detection rate
      of various genotypes of human papilloma of high carcinogenic risk established
      that the 56th and 16th types of high carcinogenic risk are revealed more often
      than others--in 33% and 15.4% correspondingly. In males, first place in
      occurrence rate is for those types of virus of human papilloma: the 56th n = 10
      (33.3%), 16th n = 3 (10%), 45th n = 3 (10%), 51th n = 3 (10%). The rest of
      genotypes are detected in 3-7% cases.

PMID- 21899118
TI  - [The production of high-yielding strain of rubella virus from wild type virus
      extracted from a patient in the Western Siberia in 2006].
AB  - The study was targeted to investigate the propagation of rubella virus in the
      cell cultures of various origins and with different cultivation methods. The high
      yielding strain of rubella virus was produced. The "spinner-culture" cultivation
      method was applied and the strain's RNA was detected in 10-8 dilution in real
      time mode. This strain is supposed to be used in preparation of the standard
      antigen to implement in the development of immune enzyme test system targeted to
      the rubella virus specific antibodies.

PMID- 21899119
TI  - [The mode of spot test of plague and pseudotuberculosis agents mix cultures].
AB  - It is supposed to implement the polymerase chain reaction with mix of two pairs
      of "chromosome" primers "vlm12for'/"IS216rev" and "JS for"/JSrev" species
      specific for Y. pestis and Y. psdtbc correspondingly in spot test of plague and
      pseudotuberculosis. The additional immunodiagnostics is applied to find defective
      and full-fledged on plague bacteria F1-antigen synthesis in the volume
      agglomeration reaction and paragglutination with diagnosticums of plasmid
      dependent F1 antigen and chromosome FV determined antigen. This mode is
      characterized by more effectiveness and lesser labor intensiveness. It
      accelerates the detection of the mix of two agents in bacterial inoculations,
      organs bioassays and other materials. Also this mode facilitates the analysis of
      mix cultures of agents of plague and pseudotuberculosis, obtained in "mixed"
      nidi, the component identification, differentiation and isolation of pure growths
      of both Yersinia.

PMID- 21899120
TI  - [On the issue of cooperation in organizing the laboratory medicine education].
AB  - In the Omsk public medical Academy, the informational and technological support
      of laboratory medicine education at undergraduate and postgraduate stages
      required to organize the cooperation between the Russian Association of medical
      laboratory diagnostics and the Academy course of clinical diagnostics. The non
      commercial interaction was organized between the Academy and the manufacturers
      and suppliers of laboratory diagnostic systems. This approach permitted to
      implement the cycle of scientific educational forums and to start the territorial
      program of quality management in laboratory research. The choice of the specialty
      "clinical laboratory diagnostics" as a prospective profession significantly
      increased among the Academy graduates. In addition, the Russian Association of
      medical laboratory diagnostics and the Omsk public medical Academy started a new
      joint project targeted to the support of laboratory diagnostics techniques
      training in concordance with the new public educational standard of higher
      professional education. Thereby, a specified model of joint resolution of actual
      issues is developed in the field of laboratory medicine education with
      coordinator collaboration of Russian Association of medical laboratory
      diagnostics as a professional non-government organization.

PMID- 21899121
TI  - [The Decree of Government of the Russian Federation No 1230 from December 31
      2010].

PMID- 21899122
TI  - [Clinical study of forty-two patients who underwent resection for pulmonary
      adenosquamous carcinoma].
AB  - Pulmonary adenosquamous carcinoma is a rare malignant tumor as defined by the
      Japan Lung Cancer Society Classification. At our institution, of the 1,023
      patients who underwent resection for primary lung cancer, 42 (4.0%) had
      adenosquamous carcinoma. Here, we present the clinical features of this malignant
      tumor. The male : female ratio was low. Many tumors were located peripherally,
      and the positive rate for carcinoembryonic antigen (CEA) was 54.8%; these
      clinical findings were similar to those of adenocarcinoma. On the other hand,
      many tumors had relatively large diameter, and most of the patients were heavy
      smokers; these findings were consistent with those of squamous cell carcinoma.
      Hence, the cases of adenosquamous carcinoma had the characteristics of both
      adenocarcinoma and squamous cell carcinoma. The prognosis of patients with
      adenosquamous carcinoma was poorer than those of patients with adenocarcinoma and
      those with squamous cell carcinoma, irrespective of whether it was stages I or
      II. Adenosquamous carcinoma is characterized by a highly aggressive biological
      behavior and a high rate of early metastasis. Therefore, even if the diagnosis is
      made at an early phase, an aggressive approach, including adjuvant chemotherapy,
      might be necessary for adenosquamous carcinoma.

PMID- 21899123
TI  - [Long-term outcome of aortic valve replacement with annular enlargement].
AB  - BACKGROUND: The choice of appropriate treatment in children with aortic valvular
      lesions remains controversial. The purpose of this study is to assess early and
      late outcomes of aortic valve replacement with annular enlargement in children.
      METHODS: A retrospective study was conducted in 16 consecutive patients aged 0.26
      to 15.9 years operated on between 1993 and 2008. Thirteen children underwent
      aortic valve replacement with Konno procedure (mechanical valve: 12, homograft:
      1), 2 children underwent Ross procedure, and the last child underwent Nicks
      procedure with mechanical valve replacement. All patients undergoing mechanical
      valve replacement were given warfarin with a monthly international normalized
      ratio (INR) control. RESULTS: Overall early mortality was 12.5% (2 cases).
      Emergency operation was performed in these cases because of infectious
      endocarditis and acute cardiac failure. However, cardiopulmonary bypass (CPB)
      weaning could not be obtained. There was 1 late death 5 months after mechanical
      valve replacement. The patient developed methicillin-resistant Staphylococcus
      aureus (MRSA) sepsis after cleft palate repair. Reoperation was needed in 1 case.
      CONCLUSION: We conclude that mechanical valve replacement with aortic annular
      enlargement is an acceptable treatment in children. It is associated with
      acceptable mortality and low incidence of late events, and provides long-term
      survival.

PMID- 21899124
TI  - [Emergency stent placement after descending aortic replacement with chronic
      aortic dissection].
AB  - A 49-year-old man with asymptomatic chronic aneurysmal dissection was admitted to
      our hospital. He had undergone ascending aortic replacement for type A aortic
      dissection 7 months before. We performed descending aortic replacement for
      chronic aneurysmal dissection. Renal dysfunction appeared 1 day after the
      operation. Contrast-enhanced computed tomography indicated that the true lumen
      was severely compressed by a false lumen, and that the origins of the renal
      artery were occluded. We performed emergency endovascular stent placement to
      dilate the true lumen. Immediately after this procedure, renal ischemia improved.
      The postoperative course was uneventful. An endovascular approach using bare
      stent can be a treatment option that is less invasive and prompter for a patient
      with renal ischemia resulting from aortic dissection.

PMID- 21899125
TI  - [Open stent-grafting using the Matsui-Kitamura stent for a distal arch aneurysm;
      an idea for insertion of stent graft and organ protection].
AB  - For the improvement in the clinical results of open stent-grafting, the
      development of a device system and prevention of spinal cord injury are
      important. For that reasons, we devised 2 methods for the open stent-grafting
      with the Matsui-Kitamura (MK) stent. First, the applicator using transesophagial
      echo transducer cover made insertion of the stent-graft system easy and safe.
      Next, to prevent ischemic spinal injury and protect major abdominal organ, blood
      return to lower body was established from femoral artery with occluding the stent
      graft by balloon. However, these procedures might need to examine whether it
      really contributes to the improvement in the clinical results.

PMID- 21899126
TI  - [Invasive pulmonary aspergillosis with hemoptysis; a resected case whose bleeding
      point is detected pathologically].
AB  - A 55-year-old man, who presented with recurrent episodes of hemoptysis, was
      referred to our hospital under the diagnosis of invasive aspergillosis with a
      cavity in the right lung. Computed tomography showed a large thick-walled cavity
      in the right upper lung. He underwent right upper lobectomy. Pathological
      findings showed a large cavity in right upper lobe. Aspergillus was found in the
      cavity. A pseudoaneurysm, which was thought to be a cause of hemoptysis,
      originated from a ruptured pulmonary artery and protruded into the cavity.
      Hemoptysis is well-known symptom in aspergillosis patients, and surgery for
      aspergillosis with hemoptysis is sometimes performed. But it is very rare that
      bleeding point is detected microscopically.

PMID- 21899127
TI  - [Extended aortic arch replacement through gull-wing approach to Kommerell's
      diverticulum and aneurysmal right-sided aortic arch with aberrant left subclavian
      artery].
AB  - The patient was a 76-year-old man. He was referred to our hospital to treat
      Kommerell's diverticulum and aneurysmal right-sided aortic arch with aberrant
      left subclavian artery. We performed extended aortic arch replacement using gull
      wing approach. He was discharged uneventfully without any complication. Gull-wing
      approach method has an advantage of wide surgical field and may be useful for
      extensive thoracic aortic disease.

PMID- 21899128
TI  - [Ebstein's anomaly in an adult].
AB  - A 56-year-old female who had been diagnosed with Ebstein's anomaly was admitted
      with cyanosis and congestive heart failure. The echocardiogram showed severe
      tricuspid valve incompetence, displacement of the tricuspid valve and dilatation
      of the atrialized portion of the right ventricle. Atrial fibrillation was
      detected in the electrocardiogram. She underwent tricuspid valve replacement and
      right atrial maze procedure. She is released from congestive heart failure and
      remains in sinus rhythm 48 months after the operation.

PMID- 21899129
TI  - [Thymic metastasis of laryngeal cancer].
AB  - A 70-year-old man visited the Department of Head and Neck Surgery with a chief
      complaint of dysphagia. A tumor was observed in the epiglottis and vocal cord,
      and was diagnosed as squamous cell carcinoma by biopsy. Computed tomography (CT)
      showed a tumor mainly in the vocal cord. CT scans revealed a tumor centered on
      the vocal cord, with bilateral cervical lymph node metastases and a well
      circumscribed 20-mm tumor in the anterior mediastinum. Fluorodeoxyglucose
      positron emission tomography (FDG-PET) showed uptake in the primary lesion, left
      cervical lymph nodes, and anterior mediastinal tumor, which suggested a lymph
      node metastasis but did not exclude thymoma. The patient underwent video-assisted
      thoracic surgery (VATS) resection of the anterior mediastinal tumor with total
      laryngectomy, total thyroidectomy, and bilateral cervical lymph node dissection.
      The final pathological diagnosis was laryngeal cancer (glottic cancer, pT4aN2M1,
      pStage IVC) with thymic metastasis (presenting as an anterior mediastinal tumor).
      Thymic metastasis of laryngeal cancer is rare, and appears difficult to
      preoperatively differentiate from other mediastinal tumors.

PMID- 21899130
TI  - [Secondary pulmonary hypertension due to pulmonary tumor thrombotic
      microangiopathy diagnosed by open lung biopsy].
AB  - A 67-year-old woman was admitted with progressive exertional dyspnea. Arterial
      blood gas analysis showed severe hypoxia. A chest radiograph and a computed
      tomography showed bilateral interstitial infiltrations and patchy ground-grass
      opacities. Initially, she was given antibiotics with no effect. Since
      transthoracic echocardiography revealed right ventricular overload, cardiac
      catheterization was performed, which showed pulmonary hypertension. Pulmonary
      angiography revealed irregular filling defects along with pulmonary peripheral
      sites. Open lung biopsy was performed to establish a definitive diagnosis and to
      treat the diffuse lung disease. Microscopically, multiple tumor thrombi of
      mucinous adenocarcinoma were found in small sized pulmonary artery. Primary sites
      of malignancy has not been found in spite of postoperative examinations.

PMID- 21899131
TI  - [Off-pump coronary artery bypass grafting with large cerebral infarction; report
      of a case].
AB  - A 48-year-old male was consulted to our hospital on the next day when he was
      developed acute myocardial infarction (AMI). He developed cerebral infarction 26
      years ago, and had left hemiparesis. Coronary angiogram revealed left main trunk
      and 2 vessels disease which was not amenable to catheter intervention, and brain
      computed tomography (CT) showed a very large infarction in right cerebrum. Off
      pump coronary artery bypass grafting (OPCAB) double bypass grafting was
      performed. The paralysis did not get worse in the post operative course. He was
      discharged to his home. If the cerebral infarction is chronic phase with
      preserved neurological function, OPCAB may be recommended, even if it is large
      infarction.

PMID- 21899132
TI  - [Surgical treatment in an adult with coronary artery aneurysm at proximal site of
      left anterior descending artery; report of a case].
AB  - A 52-year-old man was admitted to our hospital with complaint of chest pain and
      abnormal electrocardiogram (ECG) findings showing ST depression in V2-V6.
      Coronary computed tomography (CT) and coronary arteriography (CAG) showed
      coronary artery aneurysm at #5 [left main trunk (LMT)] 20 mm, #11 [circumflex
      artery (Cx)] 8.3 mm, RV branch 4 mm, and severe stenosis at #5 and #11.
      Therefore, his chest pain was due to thromboembolism from coronary artery
      aneurysm. In the present case, Kawasaki disease was not diagnosed in childhood.
      Coronary artery aneurysms were rare in the elderly and were usually found in
      association with Kawasaki disease. Morphological evaluation findings strongly
      suggested that the coronary artery aneurysm were related to Kawasaki disease.
      Resection of coronary artery aneurysm and coronary artery bypass grafting [left
      internal thoracic artery (LITA) to #8 and saphenous vein graft (SVG): aorta (Ao)
      to #14] were successfully performed. We report a case of coronary artery
      aneurysms presumed to be due to childhood Kawasaki disease in an elderly man.

PMID- 21899133
TI  - [Ruptured thoracic aortic aneurysm complicated by acute aortic dissection and
      aortic valve regurgitation; report of a case].
AB  - An 87-year-old man was found loss of consciousness after falling. He was found in
      a state of shock. Computed tomography showed rupture of aneurysm of the ascending
      aorta and aortic arch with acute aortic dissection. Echocardiography revealed
      aortic valve regurgitation and cardiac tamponade. As the result of emergency
      operation, a large hematoma in the mediastinum and pleural cavity as well as
      massive serous pericardial effusion were found. The dissection was seen in
      aneurysm of the ascending aorta and aortic arch with an intimal tear located in
      the aortic arch. After aortic valve replacement was performed, the ascending
      aorta and aortic arch were replaced, and reconstruction of 3 cervical vessel
      branches was performed under deep hypothermic circulatory arrest with selective
      cerebral perfusion. Despite the complex clinical state and serious condition in
      the elderly patient, emergency surgery saved the life of the patient without
      complications.

PMID- 21899134
TI  - [Pulmonary metastasis fifteen years after hysterectomy for uterine
      leiomyosarcoma; report of a case].
AB  - A 75-year-old woman who had undergone a hysterectomy for uterine leiomyosarcoma
      15 years before was noted to have a lung tumor on chest radiography. Chest
      computed tomography (CT) showed a tumor mass, 3.5 cm in size, in her left lung
      (S10). CT-needle aspiration biopsy revealed sarcoma We performed a left lower
      lobectomy, as there was no distant metastasis. The histopathological diagnosis
      was a metastasis of uterine leiomyosarcoma. The disease-free interval for this
      case was 15 years, which was. to our knowledge, the longest among previous
      reports of pulmonary metastasis of uterine leiomyosarcoma.

PMID- 21899135
TI  - [Bilateral pulmonary metastases from hepatocellular carcinoma successfully
      treated by surgical resection and stereotactic radiotherapy; report of a case].
AB  - We report a case of 68-year-old-man with pulmonary metastases from hepatocellular
      carcinoma (HCC). Following right hepatic lobectomy in January 2005, 4 pulmonary
      metastases in the right lung were detected by chest computed tomography (CT) in
      September 2007. As chemotherapy was not effective, surgical resection (right
      upper lobectomy, partial resection of middle and lower lobe ) was performed.
      Secondary metastases in the left lung was detected in March 2008, and
      stereotactic radiotherapy was performed considering the site of tumor location
      and poor pulmonary function. Two years after radiotherapy, the patient is alive
      without recurrence.

PMID- 21899136
TI  - [Left traumatic diaphragmatic hernia in the postoperative state of lung cancer:
      report of a case].
AB  - We report a case of left traumatic diaphragmatic hernia in the postoperative
      state of the lung cancer. A 68-year-old man underwent video-assisted partial
      resection of the left lung for lung cancer. One year after the operation, he
      experienced an accident of falling from a tree. Chest radiograph and chest
      computed tomography revealed the stomach herniating into the left thoracic
      cavity. An emergent operation was performed by the abdominal approach. The
      stomach was returned into the abdominal cavity, and the hiatus in the central
      tendon of the left diaphragm was primarily sutured. The postoperative course was
      uneventful.

PMID- 21899138
TI  - [Dementia: progress in diagnosis and treatment; editorial, towards the
      preclinical treatment of Alzheimer disease].

PMID- 21899137
TI  - [Lung carcinoma producing carbohydrate antigen 19-9; report of a case].
AB  - A 58-year-old female was admitted to our hospital for investigation of serum
      elevation of carbohydrate antigen (CA 19-9). Computed tomography of the chest
      revealed a spiculated pulmonary nodule with the longest diameter of 3.7 cm in the
      right lower lobe. The diagnosis of lung adenocarcinoma was made. The patient
      underwent right lower lobectomy with lymphnode dissection. Histological
      examination revealed acinar type adenocarcinoma. The tumor was classified as
      stage IB with T2aN0M0. Immunohistochemically, the tumor cells stained positively
      for CA19-9. The serum CA19-9 level returned to a normal level after operation,
      but increased again with mediastinal lymphnode metastasis and brain metastasis.
      She died after an operation in 16 months.

PMID- 21899139
TI  - [Dementia: progress in diagnosis and treatment; Topics, I. Basic knowledge of
      dementia and pathophysiology; 1. The concept and pathophysiology of dementia of
      Alzheimer-type].

PMID- 21899140
TI  - [Dementia:progress in diagnosis and treatment; Topics, I. Basic knowledge of
      dementia and pathophysiology; 2. Non-Alzheimer's disease associated disorders].

PMID- 21899141
TI  - [Dementia: progress in diagnosis and treatment; Topics, II. Diagnosis; 1. Early
      diagnosis of dementia, including MCI].

PMID- 21899142
TI  - [Dementia: progress in diagnosis and treatment: Topics, II. Diagnosis; 2.
      Neuroimaging diagnosis of dementia (MRI SPECT and PET)].

PMID- 21899143
TI  - [Dementia: progress in diagnosis and treatment; Topics, III. Treatments; 1. The
      new guidelines for dementia].

PMID- 21899144
TI  - [Dementia: progress in diagnosis and treatment; Topics, III. Treatments; 2.
      Pharmacological treatment of dementia].

PMID- 21899145
TI  - [Dementia: progress in diagnosis and treatment; Topics, III. Treatments; 3. Non
      pharmacological treatment of dementia].

PMID- 21899146
TI  - [Dementia: progress in diagnosis and treatment; Topics, IV. Care for dementia
      patients; 1. A referral system between experts and general practitioners].

PMID- 21899147
TI  - [Dementia: progress in diagnosis and treatment; Topics, IV. Care for dementia
      patients; 2. Care insurance and care for dementia patients].

PMID- 21899148
TI  - [Dementia: progress in diagnosis and treatment; Topics, IV. Care for dementia
      patients; 3. How to support family caregivers of dementia patients].

PMID- 21899150
TI  - [Dementia: progress in diagnosis and treatment. Topics: V. Recent topics: 2.
      Idiopathic normal pressure hydrocephalus].

PMID- 21899149
TI  - [Dementia: progress in diagnosis and treatment; Topics; V. Recent topics; 1.
      Biomarkers for Alzheimer's disease and other dementia].

PMID- 21899151
TI  - [Dementia: progress in diagnosis and treatment; topics, V. Recent topics: 3.
      Legal protection of the demented patients].

PMID- 21899152
TI  - [Dementia: progress in diagnosis and treatment: topics, V. Recent topics; 4.
      Detection of novel dementia-related genes; 1) TDP-43].

PMID- 21899153
TI  - [Dementia: progress in diagnosis and treatment; Topics, V. Recent topics; 4.
      Detection of novel dementia-related genes; 2) Dysregulation of TGF-beta family
      signaling and hereditary cerebral small vessel disease: insight into molecular
      pathogenesis of CARASIL].

PMID- 21899154
TI  - [Discussion meeting on the collaboration network between general practitioners
      and specialists for the diagnosis and management of patients with dementia].

PMID- 21899155
TI  - [Case report: a case of cholesterol crystal embolism mimicking vasculitis].

PMID- 21899156
TI  - [Case report; thyroid hormone resistance found in a patient with neuroendocrine
      tumor].

PMID- 21899157
TI  - [Case report: a case of crowned dens syndrome during pneumonia treatment].

PMID- 21899158
TI  - [Case report; typical MR image findings in Japanese encephalitis; a case report].

PMID- 21899159
TI  - [Case report; malignant peritoneal mesothelioma with hypoglycemia suggestive of
      paraneoplastic syndrome].

PMID- 21899160
TI  - [Case report; a case of insulin autoimmune syndrome with frequent hypoglycemic
      attack].

PMID- 21899161
TI  - [Case report; usefulness of gelatin sponge for bile leakage from hilar bile duct
      after right hepatic lobe resection].

PMID- 21899162
TI  - [The cutting-edge of medicine; inflammation and development of gastrointestinal
      cancers].

PMID- 21899163
TI  - [The cutting-edge of medicine; Crow-Fukase (POEMS) syndrome: diagnosis,
      pathophysiology, and treatments].

PMID- 21899164
TI  - [The cutting-edge of medicine; autophagy in pancreatic beta cell--a novel
      pathogenic factor in diabetes].

PMID- 21899165
TI  - [The cutting-edge of medicine; catheter-based renal sympathetic denervation for
      cardiovascular diseases].

PMID- 21899166
TI  - [Series: knowledge of emergency required for internist; acute coronary syndrome:
      ACS].

PMID- 21899168
TI  - [Series: Let's think-clinical quiz (question); a 66 year-old man whose blood
      pressure control worsened recently].

PMID- 21899167
TI  - [Report from the 11th Tokai Chapter Educational Seminar: 81 year old female with
      headache and fatigue of unknown cause, developing chest pain and hemiplegia
      during treatment].

PMID- 21899169
TI  - [Series: Diagnosis at a glance].

PMID- 21899170
TI  - [Series: Clinical study from Japan and its reflections; J-BAF study].

PMID- 21899171
TI  - [Series: For attending physicians; professionalism; causality assessment between
      reported adverse events and suspected drugs].

PMID- 21899172
TI  - [Impact of oxygen toxic action on the erythrocyte membrane and possibility of
      estimating central nervous system function disturbances].
AB  - BACKGROUND/AIM; Prolonged exposure to hyperbaric oxygen leads to changes of
      erythrocytes shape as a consequence of toxic effects of oxygen on the erythrocyte
      membrane. The aim of this study was to examine the association between occurance
      of pathological forms of erythrocytes at different time from the start of
      hyperbaric oxygenation and the moment of convulsions occurrence, an
      interrelationship of different pathological forms of erythrocytes during exposure
      to hyperbaric oxygenation, as well as the correlation between the presence of
      ruptured erythrocytes and function of central nervous system (CNS) after
      completion of hyperbaric treatment. METHODS: Sixty laboratory mice, Mus musculus,
      were exposed to the wholly-oxygen pressure of 3.5 absolute atmospheres (ATA).
      Blood was collected at the 32nd, 34th, 36th, 38th and 40th minutes after the
      exposure to oxygen. Pathological forms of erythrocytes were examined by electron
      microscopy. A moment of convulsions occurrence was registered in all animals.
      After decompression neurological examinations of experimental animals were
      perfomed. The Pearson's coefficient of correlation, and linear regression
      equations for the parameters outlined in the aim of the study were calculated.
      RESULTS: Hyperbaric oxygen caused damages of erythrocytes at the 34th minute
      after beginning of the treatment. Various forms of abnormal red blood cells
      occured, and immediately before the occurrence of irreversible changes
      (erythrocyte membrane rupture) echinocyte shape was dominated. A significant
      correlation between the number of damaged red blood cells at 34th minute and
      their number at the 36th, 38th and 40th minute was found. Convulsions were
      diagnosed significantly earlier in mice with a greater number of damaged red
      blood cells (p < 0.01). There was a negative correlation between the number of
      irreversiblly damaged red blood cells (ruptured) at the 40th minute and
      neurological score in the studied animals (p < 0.05). CONCLUSION: The analysis of
      altered erythrocytes during hyperbaric oxygenation could predict a moment of
      seizures occurrence, and therefore the duration of the therapy with hyperbaric
      oxygen. Ehinocytes indicate impending rupture of red blood cells and a possible
      occurrence of seizures. An increased number of ruptured red blood cells may also
      even indicate the potential burden of CNS after cessation of hyperbaric
      oxygenation.

PMID- 21899173
TI  - Retinal periphlebitis in patients with multiple sclerosis.
AB  - BACKGROUND/AIM: Multiple sclerosis (MS) is an immune-mediated disorder of the
      central nervous system (CNS), characterized by inflammation, demyelination and
      axonal loss. Retinal periphlebitis (RP) is often present in MS patients with
      similar evolution and histopathological changes as MS lesions. The aim of this
      study was to analyze the presence of RP in MS patients during different clinical
      phases, and its connection with impairment of blood-brain barrier. METHODS: The
      study included 45 patients (26 females and 19 males) with MS. Their average age
      was 33.2 +/- 8.1 years. There were 28 patients with relapsing-remitting (RR)
      form, 7 with primary progresive (PP) and 10 with secondary progressive (SP) form
      of MS. There were 27 patients in the relapse and 18 patients in the remission
      phase. The average MS duration was 7.48 +/- 1.3 years. Ophthalmological,
      neurological and MRI examination were performed in all the patients, as well as
      cerebrospinal fluid sampling. Albumin ratio and IgG index were calculated in all
      the patients. RESULTS: There were 9 patients with RP, and 36 without it. MS
      duration was significantly longer in the RP group. RP was much more common in the
      progressive form and was not present in the remission phase of MS. Albumin ratio
      values were increased in the group with RP. IgG index and IgG synthesis according
      to Tourtellotte formula, were statistically higher in the group of patients with
      RP. The values of visual evoked potentials (VEP's) latency were significantly
      higher in the group of patients with RP. CONCLUSION: The presence of RP is a
      reliable indicator of MS activity and might be considered as a parameter for
      monitoring the disease activity and effects of the treatment.

PMID- 21899174
TI  - [The state of oral health in children at the age of 12 in Montenegro].
AB  - BACKGROUND/AIM: Oral health is very important for the function and the quality of
      human life. The aim of this study was to determine the spread of caries on the
      permanent teeth, the state of health of the periodontium and the state of oral
      hygiene in the children at the age of 12 in Montenegro. METHODS: The research was
      carried out within 2006 and included 455 primary school pupils of both sex, the
      age of 12 in the northern, midlle and southern area of Montenegro. The parameters
      used to estimate oral health condition were: mean number of decayed, missing, and
      filled teeth due to caries (DMFT), Significant Caries Index (SiC), Community
      Periodontal Index of Treatment Needs (CPITN), presence of sealants, and to
      estimate oral hygiene condition: Debris Index (Green-Vermillion) and Calculus
      Index (Green). A dental team clinically examined all the subjects in line with
      World Health Organization (WHO) methodology and criteria. All chosen children
      from the sample were checked by the standard dental diagnostic equipment (plane
      dental mirror, dental, standard CPITN periodontal probe) under the artificial
      light on the dry teeth, on the dental chair. RESULTS: The average value of Index
      DMFT at 12-year-old in Montenegro was 3.43. On average, 88.35% of the examined
      children had dental caries. The SiC Index was 6.35. Among the examined children,
      11.9% had at least one tooth with a fissure sealant. The healty periodontium had
      64% of the 12-year-old children. The average value of Debris Index was 1.086, and
      the average value of Calculus Index was 0.6508. CONCLUSION: Oral health condition
      in children at the age of 12 in Montenegro does not satisfy. Thus the importance
      of the modern preventive measures and programmes should be emphasized and applied
      through the system of primary oral protection and intensively promote oral
      health.

PMID- 21899175
TI  - Immunohistochemical study of pathological alterations of peritoneum in patients
      with terminal renal insufficiency and on peritoneal dialysis.
AB  - BACKGROUND/AIM: During peritoneal dialysis (PD) an exchange of substances between
      blood and dialysate takes place through specific histological structures of
      peritoneum. Peritoneal double-layered serous membrane has, so far, mostly been
      studied with electron microscopy on experimental animals. The aim of this study
      was to assess integrity of peritoneal tissue in end-stage renal disease (ESRD)
      and PD patients using standard light microscopy and immunohistochemical methods.
      METHODS: Peritoneal tissue biopsies were performed on 25 persons: 8 healthy
      donors during nephrectomy, 9 ESRD patients upon insertion of PD catheter, and 8
      PD patients upon removal of the catheter for medical indications. The samples
      were fixed and prepared routinely for immunocytochemical staining by standardized
      streptavidin biotin AEC method using a LSAB2 HRP kit (Dako, Denmark) for collagen
      IV and analyzed by light microscopy. RESULTS: We observed mesothelial detachment
      from lamina propria, duplicated basement membrane and much thicker blood vessel
      walls in ESRD and PD patients, compared to healthy subjects. Differences in
      histological structure, emphasized with immunostaining, indicated pathological
      alterations of peritoneal tissue in the renal patients. CONCLUSIONS:
      Imunohistochemistry can be used in studying histological alterations of
      peritoneal tissue in ESRD and PD patients. This method may indicate possible
      problems in filtration and secretion processes in this tissue.

PMID- 21899176
TI  - [Ambient temperature impact on hepatocellular liver damage in rats following
      intake of 3,4-methylenedioxymethamphetamine].
AB  - BACKGROUND/AIM: 3,4-methylendioxymethamphetamine (MDMA, Ecstasy) is a psycho
      stimulating agent. It is usually taken orally in the form of tablets. It is
      absorbed throught the gastrointestinal mucous membrane. Hyperthermia is the most
      prominent clinical sign of MDMA intake. The most prominent forensic finding of
      lethal MDMA poisoning is myocardial infarction and cerebrovascular bleeding.
      However, liver and kidney damage: have also been described. The aim of this
      research was to determine if ambient temperatures affect liver damage in the
      experimental rats. METHODS: The experiment was conducted for 8 h and 24 h, at
      temperatures of 12 degrees C, 22 degrees C and 32 degrees C. Both biochemical
      parameters (ALT, AST, AP, gamma GT and LDH) and pathohistological changes of the
      liver were monitored. RESULTS: Our reserch demonstrated that the most serious
      lever damage occurred at 32 degrees C. Liver damage was manifested as portal
      inflammation, periportal necrosis, lobular necrosis, stasis, intralobular
      hemorrhage and incerease of liver enzymes serum activity. CONCLUSION: Liver
      damage after MDMA intake rises with the increase of ambient temperature, and it
      is most pronounced at the temperature of 32 degrees C.

PMID- 21899177
TI  - Expression of regulatory proteins and proliferative activity in relation to
      phenotypic characteristics of upper urothelial carcinoma.
AB  - BACKGROUND/AIM: Deregulation of the normal cell cycle is common in upper
      urothelial carcinoma (UUC). The aim of this study was to investigate the
      expression of regulatory proteins of the cell cycle (p53, p16, cyclin D1, HER-2)
      and proliferative Ki-67 activity in UUC, and to determine their interaction and
      influence on the phenotypic characteristics of UUC. METHODS: In 44 patients with
      UUC, histopathological and immunohistochemical analyses (p53, p16, cyclin D1, HER
      2, and Ki-67) of tumors were done. RESULTS: Overexpression/altered expression of
      p53, p16, cyclin D1 or HER-2 was detected in 20%, 57%, 64%, and 57% of tumors,
      respectively. Eleven (25%) UUC had a high proliferative Ki-67 index. Forty
      patients (91%) had at least one marker altered, while four (9%) tumors had a wild
      type status. Analysis of relationship between expressions of molecular markers
      showed that only high expression of p53 was significantly associated with altered
      p16 activity (p < 0.05). High Ki-67 index was associated with the high stage (p <
      0.005), solid growth (p < 0.01), high grade (p < 0.05), and multifocality p <
      0.05) of UUC, while high expression of p53 was associated with the solid growth
      (p < 0.05). In regression models that included all molecular markers and
      phenotypic characteristics, only Ki-67 correlated with the growth (p < 0.0001),
      stage (p < 0.01), grade (p < 0.05) and multifocality (p < 0.05) of UCC; (Ki-67
      and HER-2 expression correlated with the lymphovascular invasion (p < 0.05).
      CONCLUSIONS: This investigation showed that only negative regulatory proteins of
      the cell cycle, p53 and p16, were significantly associated in UUC, while
      proliferative marker Ki-67 was in relation to the key phenotypic characteristics
      of UUC in the best way.

PMID- 21899178
TI  - Skin vascularisation field by the ascending branch of the peroneal artery ramus
      perforans.
AB  - BACKGROUND/AIM: Soft tissue defects in the distal third of the lower leg are
      persistent and constitute a major problem in the reconstructive surgery. This
      study presents an analysis of the anatomical vascularization filed of ascending
      branch of the peroneal artery ramus perforans (PARS). The aim of this study was
      to assess reliability of the distal flap on the antero-lateral aspect of a lower
      leg distal third. METHODS: Direct gentiana violet injection into the interosseal
      perforator of ten fresh cadaveric lower legs with subsequent corrosion acrylic
      preparation was performed to reveal vascularization filed of the ascending branch
      of the PARP. Height, length, diameter and communication of perforating branch and
      its subsequent smaller ascending and descending branches were determined. The
      CAMIA software was used. RESULTS: Our results show that the PARP is always
      present. Its origin from the peroneal artery is at the medial height of 66 mm
      when measured from the inferior border of the lateral malleolus. Medium length of
      ramus perforans is 51.7mm. After transition through the interosseous membrane,
      ramus perforans divides into ascending and descending branches. The diameter
      proximal to the level of bifurcation is 1.37 mm (variation 1.0-1.8 mm), and the
      diameter of the ascending branch distal to the level of bifurcation is 1 mm.
      Using CAMIA software, the medium length, width and area of the vascularization
      filed labeled with gentian violet were calculated to be 164 mm (variation 125-210
      mm), 66 mm (57-77 mm), and 10,305 mm2 (6,385 mm2-14,341 mm2), respectively.
      CONCLUSION: Our results support the use of fasciocutaneous distal flap,
      vascularized by the ascending branch of the PARP for reconstruction of soft
      tissue defects in the distal third of the lower limb, malleolar regions and
      dorsum.

PMID- 21899179
TI  - [Transvaginal mesh in repair of pelvic organs prolapse as a minimally invasive
      surgical procedure].
AB  - BACKGROUND/AIM: Prolapse of genital organs with or without urinary stress
      incontinention is the most often health problem in the elderly female population
      tending to increase with ageing. The aim of this study was to assess the
      perioperative complications and short-term outcomes of prolaps repair using
      transvaginal polypropylene mesh (Prolift system, Gynecare, Ethicon, USA).
      METHODS: A retrospective study was conducted evaluating 96 women from September
      2006 to January 2010 who underwent vaginal repair with implatation of a soft mesh
      manufactured by Gynecare, Ethicon, USA. RESULTS: All the patients had a stage 3
      or stage 4 prolapse according to the POP-Q system of ICS. Total mesh was used in
      12 (13%) patients isolated anterior mesh in 52 (54%) patients and isolated
      posterior mesh in 32 (33%) patients. We reported one intra-operative bladder
      injury and no other serious complications. At 3 months, all 96 patients were
      available for follow-up. Vaginal erosion occured in 9 (9.3%) patients, shrinkage
      of mesh in 6 (6.2%) patients and de novo urinary incontinence in 5 (5.2%)
      patients. Failure rate was 6.25% (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 and low morbidity rates. However, some
      complications are serious and require highly specialised management.

PMID- 21899180
TI  - Evaluation of the risk malignancy index diagnostic value in patients with adnexal
      masses.
AB  - BACKGROUND/AIM: Ovarian cancer is the leading cause of death from gynecologic
      malignancies. Risk of malignancy index (RMI) is recommended in assessment of
      patients with adnexal masses. The aim of this study was to verify the
      effectiveness of the RMI in the discrimination between benign lesions and
      malignant adnexal masses in clinical practice. METHODS: Ultrasounds were
      performed for all the patients and menopausal status, CA125 level and calculated
      RMI were defined. All the patients were divided into 3 groups depending on RMI (<
      25, 25-200, > 200). After operations all adnexal masses were analyzed
      histopathologically (HP) and then sensitivity, specificity and predictive value
      of RMI were calculated. RESULTS: Out of a total of 81 patients involved benign
      tumor had 51 (62.96%) and malignant 30 (37.04%) of the patients. The average
      value of CA125 in the group of patients with benign adnexal masses was 68.3 U/mL
      and in the group of patients with malignant adnexal masses it was 581.95 U/mL. In
      the group of patients with benign adnexal masses the average RMI was 284.9 and in
      the group of patients with malignant adnexal masses RMI was 469.2. All the
      results showed a positive correlation between both HP categories and RMI
      categories. The more malignant HP result produced higher RMI and the cut off
      value was RMI = 200. Sensitivity of RMI w as 83.33%, specificity was 94.12%,
      positive predictive value was 89.29% and negative predictive value was 90.57%.
      CONCLUSION: Our study showed that RMI is very reliable in differentiation benign
      from malignant adnexal masses.

PMID- 21899181
TI  - Correlation analysis of craniomandibular index and gothic arch tracing in
      patients with craniomandibular disorders.
AB  - BACKGROUND/AIM: Complex etiology and symptomatology of craniomandibular
      dysfunction make the diagnosing and therapy of this disorder more difficult. The
      aim of this work was to assess the value of clinical and instrumental functional
      analyses in diagnosing of this type of disorders. METHODS: In this study 200
      subjects were examined, 15 with temporomandibular joint disorder. They were
      subjected to clinical functional analysis (Fricton-Shiffman) and instrumental
      functional analysis by using the method of gothic arch. The parameters of the
      gothic arch records were analyzed and subsequently compared among the subjects of
      the observed groups. RESULTS: In the examined group of the population 7.5% of
      them were with craniomandibular dysfunction. The most frequent symptoms were
      sound in temporomandibular joint, painful sensitivity of the muscles on palpation
      and lateral turning of the lower jaw while opening the mouth. By analyzing the
      gothic arch records and comparing the obtained values between the observed groups
      it was assessed that: lateral and protrusion movements, lateral amplitude and the
      size of gothic arch were much bigger in the healthy subjects, and latero-lateral
      asymmetry was larger in the sick subjects. Latero-lateral dislocation of apex was
      recorded only in the sick subjects with average values of 0.22 +/- 0.130 mm. The
      correlation between the values of Fricton-Shiffman craniomandibular index and the
      parameters of the gothic arch records and latero-lateral amplitude and
      dislocation of apex records were established by correlative statistical analysis.
      CONCLUSION: Functional analysis of orofacial system and instrumental analysis of
      lower jaw movements (gothic arch method) can be recommended as precise and simple
      methods in diagnosing craniomandibular dysfunctions.

PMID- 21899182
TI  - Splenic artery pseudoaneurysm as a complication of pancreatic pseudocyst.
AB  - INTRODUCTION: Pancreatic pseudocyst presented as pseudoaneurysm of the splenic
      artery is a potential serious complication in patients with chronic pancreatitis.
      CASE REPORT: A 42-year-old male patient with a long-standing evolution of chronic
      pancreatitis and 8-year long evolution of pancreas pseudocyst was referred to the
      Military Medical Academy, Belgrade due to worsening of the general condition. At
      admission, the patient was cachectic, febrile, and had the increased values of
      amylases in urine and sedimentation (SE). After clinical and diagnostic
      examination: laboratory assessment, esophagogastroduodenoscopy (EGDS),
      ultrasonography (US), endoscopic ultrasonography (EUS), multislice computed
      scanner (MSCT) angiography, pseudoaneurysm was found caused by the conversion of
      pseudocyst on the basis of chronic pancreatitis. The patient was operated on
      after founding pancreatic pseudocyst, which caused erosion of the splenic artery
      and their mutual communication. Postoperative course was duly preceded without
      complications with one year follow-up. CONCLUSION: Angiography is the most
      reliable and the safest method for diagnosing hemorrhagic pseudocysts when they
      clinically present as pseudoaneurysms. A potentially dangerous complication in
      the presented case was treated surgically with excellent postoperative results.

PMID- 21899183
TI  - Group A streptococcal cellulitis in the early puerperium.
AB  - INTRODUCTION: Infectious diseases caused by Streptococcus pyogenes, a member of
      the group A Streptococci (GAS) are among the most common life threatening ones.
      Patients with GAS infections have a poor survival rate. Cellulitis is a severe
      invasive GAS infection and the most common clinical presentation of the disease
      associated with more deaths than it can be seen in other GAS infections.
      According to the literature data, most cases of GAS toxic shock syndrome are
      developed in the puerperium. However, there are two main problems with GAS
      infection in early puerperium and this case report is aimed at reminding on them.
      The first problem is an absence of awareness that it can be postpartal invasive
      GAS infection before the microbiology laboratory confirms it, and the second one
      is that we have little knowledge about GAS infection, in general. CASE REPORT: A
      32-year-old healthy woman, gravida 1, para 1, was hospitalized three days after
      vaginal delivery with a 38-hour history of fever, pain in the left leg (under the
      knee), and head injury after short period of conscious lost. Clinical picture of
      GAS infection was cellulites. Group A Streptoccocus pyogenes was isolated in
      vaginal culture. Rapid antibiotic and supportive treatment stopped development of
      streptococcal toxic shock syndrome (STSS) and potential multiorganic failure.
      Signs and symptoms of the infection lasted 25 days, and complete recovery of the
      patient almost 50 days. CONCLUSION: In all women in childbed with a history of
      fever early after delivery, vaginal and cervical culture specimens should be
      taken as soon as possible. Early recognition of GAS infection in early puerperium
      and prompt initiation of antimicrobial drug and supportive therapy can prevent
      development of STSS and lethal outcome.

PMID- 21899184
TI  - [Vasospastic angina pectoris complicated by acute myocardial infarction and
      complete atrioventricular block].
AB  - BACKGROUND: A prolonged coronary artery spasm with interruption of coronary blood
      flow can lead to myocardial necrosis and increase of cardiospecific enzymes and
      can be complicated with cardiac rhythm disturbances, syncopc, or even sudden
      cardiac death. CASE REPORT: A 55-year old male felt a severe retrosternal pain
      when exposing himself to cold weather. The pain lasted for 20 minutes and was
      followed by the loss of conscience. Electrocardiogram (ECG) showed a complete
      antrioventricular (AV) block with nodal rhythm and marked elevation of ST segment
      in inferior leads. Electrocardiogram was soon normalized, but serum activities of
      cardiospecific enzymes were increased. Coronarography showed normal findings for
      the left coronary artery and a narrowing at the middle part of the right coronary
      artery, which disappeared after intracoronary application of nitroglycerine. The
      following therapy was prescribed: Diltiazem, Amlodipin, Isosorbid mononitrate,
      Molisdomin, Atrovastatin, Aspirin and Nitroglycerine spray. After 7 months
      medicaments were abandoned and the patient experienced again reccurent chest pain
      episodes at rest. Transitory ST segment elevation was recorded in inferior leads
      of ECG, but without increase of cardiospecific enzymes serum activities. After
      restoration of the medicament therapy anginal episodes ceased. CONCLUSION:
      Coronary dilators in maximal doses can prevent attacks of vasospastic angina.

PMID- 21899185
TI  - Endovascular repair of posttraumatic multiple femoral-femoral and popliteal
      popliteal arteriovenous fistula with Viabahn and excluder stent graft.
AB  - BACKGROUND: Traumatic arteriovenous (AV) fistula is considered to be a pathologic
      communication between the arterial and venous systems following injury caused
      mostly by firearms, sharp objects or blasting agents. Almost 50% of all traumatic
      AV fistulas are localized in the extremities. In making diagnosis, besides injury
      anamnesis data, clinical image is dominated by palpable thrill and auscultator
      continual sounds at the site of fistula, extremities edemas, ischemia distally of
      fistula, pronounced varicose syndrome, and any signs of the right heart load in
      high-flow fistulas. CASE REPORT: We presented a male 32-year-old patient self
      injured the region of the right lower and upper leg by shotgun during hunting in
      2005. The same day the patient was operated on in a tertiary traumatology health
      care institution under the diagnosis of vulnus sclopetarium femoris et cruris
      dex; AV fistula reg popliteae dex; fractura cruris dex. The performed surgery was
      ligatura AV fistulae; reconstructio a. popliteae cum T-T anastomosis; fasciotomia
      cruris dex. Postoperatively, in the patient developed a multiple AV fistula of
      the femoral and popliteal artery and neighboring veins. The patient was two more
      times operated on for closing the fistula but with no success. Three years later
      the patient was referred to the Clinic for Vascular Surgery, Military Medical
      Academy, Belgrade, Serbia. A physical examination on admission showed the right
      upper leg edema, pronounced varicosities and high thrill, signs of the skin
      induration and initial ischemia with ulceration in the right lower leg, as well
      as numerous scars in the inner side of the leg from the previously performed
      operations. Due to the right heart load there were also present easy getting
      tired, tachypnoea and tachycardia. CT and contrast angiography verified the
      presence of multiple traumatic AV fistulas in the surface femoral and popliteal
      artery and neighboring veins of the highest diameter being 1 cm. Also, numerous
      metallic balls--grains of shotgun were present. After the preoperative
      preparation under local infiltrative anesthesia, transfemoral endovascular
      reconstruction was done of the surface femoral and popliteal artery by the use of
      stent grafts Viabahn 6 x 50 mm and excluder PXL 161 007. Within the immediate
      postoperative course a significant reduction of the leg edema and disappearance
      of thrill occurred, and, latter, healing of ulceration, and disappearance of
      signs of the foot ischemia. Also, patient's both cardiac and breathing functions
      became normal. CONCLUSION: In patients with chronic traumatic AV fistulas in the
      femoropopliteal region, especially with multiple fistulas, the gold standard is
      their endovascular recon struction which, although being minimally traumatic and
      invasive, offers a complete reconstruction besides keeping integrity of both
      distal and proximal circulation in the leg.

PMID- 21899186
TI  - Serbian painters in the Army Medical Corps 1914-1918.

PMID- 21899187
TI  - [Resignation of the president and uncertainty for the National Nurse
      Organization].

PMID- 21899188
TI  - [Reform of the dependence, the Chief of State announced at the reopening].

PMID- 21899189
TI  - [Surgical treatment of heart valve diseases and its complications].

PMID- 21899190
TI  - [Postoperative care of the heart valve replacement patient].

PMID- 21899191
TI  - [Patient education of those patients on anti-vitamin K therapy].

PMID- 21899193
TI  - [Nursing care and the need for spirituality].

PMID- 21899192
TI  - [A course of care guided by the passion for nursing care and the love for
      others].

PMID- 21899194
TI  - [Clinical consultation and description of musculoskeletal pain].

PMID- 21899195
TI  - [Reflexions on the emergence of the right to practice lethal injections].

PMID- 21899196
TI  - [From plasterer to gypsotherapy nurse].

PMID- 21899197
TI  - [Promoting the collaboration between the nurses' aide and the nurse during the
      use of MEOPA].

PMID- 21899198
TI  - [Teaching dedicated to the analysis of clinical situations].

PMID- 21899199
TI  - [Urinary catheterization].

PMID- 21899200
TI  - Admitting a child into the pediatric ward.

PMID- 21899201
TI  - [Mourning].

PMID- 21899202
TI  - [If you can't go to school, school will come to you!].

PMID- 21899203
TI  - Synthesis and pharmacological evaluation of some quinoline derivatives as
      potential cognition enhancers.
AB  - The present paper describes the synthesis of a series of substituted 6-amino (1a
      c) and 8-aminoquinoline derivatives (2b-c) and the evaluation of their ability to
      prevent the memory decline using a behavioural model, i.e. the elevated plus maze
      test. The effect of the candidate drugs on the activity of acetylcholinesterase
      was studied using the enzyme source from the mouse brain. The structures of the
      synthesized compounds were confirmed by UV, IR, 1H-NMR and elemental analysis.
      The 6-aminoquinoline derivative [6-(4-pyridyl)methylaminoquinoline] (1c) oxalate
      showed maximum % retention (50% at 5 mg/kg and 75% at 10 mg/kg) in the elevated
      plus maze test and maximum % inhibition (71% at 25 microM) of AChE on biochemical
      evaluation.

PMID- 21899204
TI  - Synthesis and biological evaluation of some novel quinoxaline derivatives as
      anticonvulsant agents.
AB  - In view of their expected anticonvulsant activity, some new derivatives of
      quinonxaline (V1-7) were designed and synthesized by condensation of different
      aromatic aldehydes with 2-(2-oxo-3-phenylquinoxalin-1(2H)-yl)acetohydrazide (IV).
      All synthesized compounds were isolated and confirmed by IR, 1H-NMR, MS,
      elemental analysis and then tested as anticonvulsant agents. Compound V3 and V1
      showed the highest anticonvulsant effect with anticonvulsant potency relative to
      phenobarbital sodium of 0.8 and 0.75 whereas compound V5 exhibited the lowest
      relative potency of 0.09. The other compounds showed variable activity between
      these values as follows: V2 = 0.19, V4 = 0.41, V6 = 0.1 and V7 = 0.15. All
      compounds showed less activity than the reference compound phenobarbital. But the
      compounds provided a basis for further optimization.

PMID- 21899205
TI  - Effect of mangiferin, a naturally occurring glucoxylxanthone, on fear memory in
      rats.
AB  - Mangiferin (1,3,6,7-tetrahydroxy-2-[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] 
      xanthen-9-one, CAS 4773-96-0), a naturally occurring glucosylxanthone, is widely
      distributed in higher plants and a constituent of folk medicine. In the present
      study the effect of systemic administration of mangiferin on behavioural outcomes
      of neurological function in normal rats was investigated. A single
      intraperitoneal injection of mangiferin (10, 50 and 100 mg/kg body weight)
      immediately post-training produced an impairment of long-term memory for aversive
      training and a reduced freezing in a dose independent manner, when given
      immediately post-training. The administration of mangiferin 6 h post-training did
      not affect fear memory. The results indicate that mangiferin might induce
      deficits of emotionally motivated memory.

PMID- 21899206
TI  - Effects of calcium antagonists and agonists on isolated human v. saphena magna
      used for coronary artery bypass grafting and guinea pig's papillary muscle.
AB  - BACKGROUND: The goal of this study was to investigate the movement of contraction
      relaxation effects on isolated human blood vessel samples by the actions of
      amlodipine (CAS 88150-42-9), cerebrocrast (CAS 118790-71-9), diltiazem (CAS 42399
      41-7), and a benzimidazole derivative. Additionally, their effects on isometric
      contraction force and the duration of the action potential (AP) were measured.
      METHODS: The experiments were carried out on isolated human v. saphena magna
      samples and papillary muscles of adult guinea pigs. Isometric contraction and the
      AP were recorded using a force transducer and standard microelectrode technique.
      RESULTS: Phenylephrine (10(-4) M) caused contractions of vein rings to 928 +/-
      76.5 mg. All the tested agents at a concentration of 10(-7)-10(-4) M
      significantly relaxed the smooth muscle in a dose-dependent manner. The weakest
      response was shown by amlodipine. Pre-treatment with 50 microM of amlodipine,
      diltiazem and benzimidazole for 30 min significantly increased the magnitude of
      the contraction induced by phenylephrine in concentration-dependent (10(-6)-10(
      4) M) fashion but only in the benzimidazole group versus other tested agents and
      the control. The benzimidazole derivative caused augmentation of isometric
      contraction of the papillary muscles and negligible lengthening of AP duration;
      the other agents tested showed opposite effects. CONCLUSION: These results show
      that agents possessing positive or negative inotropic action significantly
      relaxed the isolated vein samples precontracted with phenylephrine. These
      responses point to a different mechanism of action underlying both calcium
      antagonist and agonist effects even though their action ultimately resulted in
      vasodilatation.

PMID- 21899207
TI  - Relative bioavailability and pharmacokinetic study of two trimetazidine modified
      release formulations in healthy Bangladeshi male volunteers.
AB  - Trimetazidine (CAS 5011-34-7) is an effective and well-tolerated antianginal drug
      that possesses protective properties against ischemia-induced heart injury. The
      relative bioavailability and pharmacokinetic characteristics of two modified
      release formulations of 35 mg trimetazidine, one as the test product (Metacard
      MR) and one as the reference product, were compared in healthy Bangladeshi male
      volunteers. The randomized, two-way crossover study was conducted in 24 healthy
      male volunteers after administration of a single 35 mg dose of each modified
      release formulation after 12-h overnight fasting, with a washout period of two
      weeks. Blood samples were collected at various time intervals following oral
      administration and analyzed for trimetazidine concentrations using a validated
      HPLC method. The pharmacokinetic parameters were determined by a non
      compartmental method. After administering a single dose of 35 mg of each
      trimetazidine formulation, the obtained mean (SD) values for the test and
      reference products were 104.78 (29.3) and 98.57 (28.7) ng/ml for Cmax; 4.00 (1.1)
      and 3.54 (1.32) h for t(max); 423.81 (173.9) and 410.01 (195.87) ng x h/ml for
      AUC0-12; and 472.51 (195.2) and 462.78 (225.13) ng x h/ml for AUC0-infinity
      respectively. The mean t1/2 was found 3.69 (1.1) h and 3.45 (0.72) h for test and
      reference products respectively. From paired t-test, no significant differences
      were observed (p > 0.05) for any pharmacokinetic parameters. The 90% confidence
      intervals of the test/reference mean ratios of the In-transformed AUC0-12, AUC0
      infinity, and Cmax mean values were 106.19% (97.16%-116.06%), 104.74% (95.04%
      115.42%) and 106.30% (95.23%-118.66%), respectively. The two formulations
      demonstrated similar bioavailability with respect to both the rate and extent of
      trimetazidine absorption.

PMID- 21899208
TI  - Assessment of the extent of oxidative stress induced by intravenous ferumoxytol,
      ferric carboxymaltose, iron sucrose and iron dextran in a nonclinical model.
AB  - Intravenous (i.v.) iron is associated with a risk of oxidative stress. The
      effects of ferumoxytol, a recently approved i.v. iron preparation, were compared
      with those of ferric carboxymaltose, low molecular weight iron dextran and iron
      sucrose in the liver, kidneys and heart of normal rats. In contrast to iron
      sucrose and ferric carboxymaltose, low molecular weight iron dextran and
      ferumoxytol caused renal and hepatic damage as demonstrated by proteinuria and
      increased liver enzyme levels. Higher levels of oxidative stress in these tissues
      were also indicated, by significantly higher levels of malondialdehyde,
      significantly increased antioxidant enzyme activities, and a significant
      reduction in the reduced to oxidized glutathione ratio. Inflammatory markers were
      also significantly higher with ferumoxytol and low molecular weight iron dextran
      rats than iron sucrose and ferric carboxymaltose. Polarographic analysis
      suggested that ferumoxytol contains a component with a more positive reduction
      potential, which may facilitate iron-catalyzed formation of reactive oxygen
      species and thus be responsible for the observed effects. Only low molecular
      weight iron dextran induced oxidative stress and inflammation in the heart.

PMID- 21899209
TI  - A simple and sensitive liquid chromatography method for the determination of low
      dihydrocodeine concentrations in human plasma: its application in Chinese healthy
      volunteers.
AB  - A simple, sensitive and modified method was developed for determination of low
      dihydrocodeine (CAS 125-28-0) concentrations in human plasma by high performance
      liquid chromatography (HPLC) with diode array detector. Measurement was performed
      on a Zorbax XDB-C18 analytical column together with a XDB-C18 precolumn at 40
      degrees C after a simple one-step extraction. An isocratic mobile phase
      consisting of acetonitrile-0.1% trifluoroacetic acid (TFA)-water (12:40:48,
      v/v/v), was run at a flow rate of 1.0 mL/min. Good chromatographic separation was
      achieved in less than 6.2 min. This assay was linear over a concentration range
      of 2.50-100 ng/mL with a lower limit of quantification at 2.50 ng/mL. The intra-
      and inter-day precision (relative standard deviation) was less than 6.00 and
      6.62%, respectively, at all concentration levels studied, while the intra- and
      inter-day accuracy was 1.50-3.73% and -1.35-1.92%, respectively. Recoveries were
      76.10-83.81% with coefficients of variation of 1.86-6.93%. Stability of
      dihydrocodeine in plasma proved to be good. The validated method was successfully
      applied to a bioequivalence study of dihydrocodeine after a single oral
      administration of 20 mg dihydrocodeine tartrate in Chinese healthy male
      volunteers.

PMID- 21899210
TI  - Pharmacokinetics of betamethasone and betamethasone 17-monopropionate in Chinese
      healthy volunteers after intramuscular injection of betamethasone
      phosphate/betamethasone dipropionate.
AB  - The aim of this study was to evaluate the pharmacokinetic profiles of
      betamethasone (BOH, CAS 378-44-9) and betamethasone 17-monopropionate (B17P), the
      active metabolites of betamethasone phosphate (BSP) and betamethasone
      dipropionate (BDP), respectively, after administration of betamethasone i.m. (BSP
      2 mg and BDP 5 mg). After ten healthy volunteers had received a single-dose
      intramuscular adminitration of betamethasone i.m., blood samples were collected
      pre-dose and for 336 h postdose. The plasma levels of B17P and BOH were measured
      by liquid chromatography-tandem mass spectrometry (LC-MS/ MS). When compared to
      BOH, B17P exhibited a longer time to maximum concentration (15.0 +/- 9.0 h vs.
      2.8 +/- 1.7 h), a lower Cmax (0.6 +/- 0.2 ng/mL vs. 14.5 +/- 3.7 ng/mL), and a
      much longer half-life (80.8 +/- 22.7 h vs. 9.6 +/- 3.6 h). Betamethasone i.m.
      produced rapid onset and sustained action through an initial rapid-increased
      plasma concentration of BOH and a sustained plasma concentration of B17P,
      respectively.

PMID- 21899211
TI  - Usefulness of suplatast tosilate, a Th2 cytokine inhibitor based on the Th1/Th2
      ratio for allergic disease in children: a retrospective study.
AB  - BACKGROUND: Children with an atopic predisposition are presumed to have
      persistent Th2 dominance and thus develop allergic diseases. METHODS: A total of
      45 children who fell to atopic dermatitis and/or intermittent asthma or mild
      persistent asthma between 2002 and 2007 were enrolled and retrospectively
      analyzed. Twenty-four children were administered oral treatment with the
      immunopharmacological drug suplatast tosilate (CAS 94055-76-2) at a dose of 3
      mg/kg twice daily. Twenty-one of the control group were not administered oral
      suplatast tosilate but treated with other drugs. Blood was collected before and
      after administering suplatast tosilate or other drugs, and Th1 cells, Th2 cells,
      the Th1/Th2 ratio, the total IgE levels, and the eosinophil count were measured.
      RESULTS: In the suplatast tosilate group, Th1 cells increased to 7.9 (1.2-19.8) %
      from 5.5 (1.1-13.5) % (Wilcoxon P < 0.05), while the Th2 cells showed a decrease
      from 1.3 (0.5-6.5) % to 1.6 (0.4-2.9) %, but the differences were not
      significant. The Th1/Th2 ratio increased significantly from 4.1 (0.9-7.4) to 5.6
      (1.3-15.5) (shifting to Th1 dominance) in the suplatast tosilate group (Wilcoxon
      P < 0.05), while it shifted to Th2 dominance in the control group (increased from
      4.5 (2.2-12.2) to 5.7 (1.6-11.8)) but did not show significant difference.
      CONCLUSIONS: The Th1/Th2 ratio increased significantly after administration of
      suplatast tosilate, shifting to Th1 dominance. Therefore suplatast tosilate
      improves Th2 dominance and may inhibit subsequent progression of allergy over the
      long term.

PMID- 21899212
TI  - Liquid chromatographic tandem mass spectrometric assay for simultaneous
      quantification of compound 97/78 and its in vivo metabolite 97/63, a novel
      trioxane antimalarial, in human plasma and its application to a protein binding
      study.
AB  - A sensitive, selective and specific LC-MS/ MS assay for simultaneous
      quantification of compound 97/78 and its active in vivo metabolite 97/63, a novel
      1,2,4-trioxane antimalarial, in human plasma has been developed and validated
      using alpha-arteether as internal standard (IS). Extraction from plasma involves
      a simple protein precipitation method. The analytes were chromatographed on a
      Columbus C18 column with guard by isocratic elution with acetonitrile:ammonium
      acetate buffer (10 mM, pH 4.0) (80:20 v/v) as mobile phase at a flow rate of 0.45
      mL min(-1) and analyzed in multiple reaction-monitoring (MRM) positive ion mode.
      The chromatographic run time was 4.0 min. The weighted (1/x2) calibration curves
      were linear over a range of 1.56-200 ng mL(-1) with correlation coefficients >
      0.998. For both analytes, the limit of detection (LOD) and lower limit of
      quantification (LLOQ) were 0.5 ng mL(-1) and 1.56 ng mL(-1), respectively. The
      recovery of 97/78, 97/63 and IS from spiked control samples were > 90% and their
      matrix suppression obtained were < 8 %. The accuracy (% bias) and precision
      (%RSD) for both analytes were < 6.78%. Both analytes were stable after three
      freeze-thaw cycles (% deviation < 12.80), long-term for 30 days in plasma at -60
      degrees C (% deviation < 14.38), for 8 h on bench top in plasma at ambient
      temperature (% deviation < 1.52) and also in the auto-sampler for 12 h (%
      deviation < 3.9%). The validated method was successfully applied to a protein
      binding study of compound 97/78 and metabolite 97/63 in human plasma.
      Furthermore, the validated method will be applicable to pharmacokinetics,
      bioavailability and metabolism in various clinical phases and in drug interaction
      studies.

PMID- 21899213
TI  - [Clinical pathology versus forensic pathology].

PMID- 21899214
TI  - [Targeted therapy in lung cancer: molecular testing using cytological specimens].
AB  - Important advances in lung cancer treatment have been made over the last decade.
      Several drugs designed to target molecular pathways involved in cancer-cell
      growth and survival have been shown to be effective in a selected fraction (<20%)
      of non-small cell lung cancer patients. Somatic mutations in several genes (i.e.:
      EGFR and KRAS) can predict patient's response to targeted therapies. Those
      mutations are commonly detected on histopathological samples (core-needle biopsy/
      surgical resection). However, when tissue biopsies are not available, molecular
      testing has to be performed on cytological specimens. Issues raised by molecular
      testing on cytological specimen are discussed in this article.

PMID- 21899215
TI  - [Fine needle aspiration of the thyroid: the value of on-site evaluation].
AB  - Thyroid nodules are very common in the general population and most of them are
      benign. Fine needle aspiration (FNA) of the thyroid is routinely used because it
      is a rapid, simple, accurate and cost-effective technique which allows the
      adequate selection of patients who should be managed surgically. However, the
      diagnostic yield of FNA is variable and depends of multiple factors including the
      one who performs FNA, the aspiration and cytological slide preparation
      techniques, and cytopathologist's experience. On-site evaluation of thyroid FNA
      material and close clinico-pathological collaboration offer many advantages and
      optimizes the yield of FNA.

PMID- 21899216
TI  - [Trophoblastic diseases: a multidisciplinary approach, a first Swiss center].
AB  - Trophoblastic diseases are rare and complex. The Center for trophoblastic
      diseases, the first in Switzerland, was founded in Geneva in January 2009 to
      formalize the collaboration between obstetricians-gynecologists, pathologists,
      geneticists, radiologists and oncologists. At the physician's request and with
      patient consent, an integrative diagnosis is proposed after centralized review of
      the histological slides, anti-p57KIP2 immunohistochemistry, and ploidy analysis
      by QF-PCR (Quantitative fluorescent polymerase chain reaction). The referring
      physician receives treatment and beta-hCG dosage recommendations. This
      pluridisciplinary diagnostic and therapeutic approach allows optimal surveillance
      and treatment of patients.

PMID- 21899217
TI  - [Lynch syndrome: when pathologist and clinician have the opportunity to reduce
      the risk of developing cancer].
AB  - Lynch syndrome is an autosomal dominant disease associated with an important risk
      of cancer, mainly endometrial and colorectal-cancer. This risk can be efficiently
      lessen by an appropriate screening as far as the mutations carriers are
      identified. As current clinicopathological recommendations lack sensitivity, a
      systematic pre-screening of every patient with a colorectal or endometrial cancer
      can be proposed. Oncogenetic units of the HUG in Geneva and ICHV in Valais have
      set up a population-based study to evaluate the efficacy of such a strategy.
      Whatever the approach, the pathologist is directly implicated as Lynch syndrome
      harbors specific histological aspects that can help to its identification, but
      also as pre-screening tests are directly realized on tumor-tissue.

PMID- 21899218
TI  - [Post-mortem angio-CT: a new diagnostic approach].
AB  - Post-mortem CT-angiography is a minimally invasive exam that allows the
      investigation of the vascular system in a very detailed way, impossible to
      realize during conventional autopsy. The research group for post-mortem angio-CT
      in Lausanne has developed a standardized protocol fora technique called "multi
      phase post-mortem CT-angiography" that leads to an easy applicable performance of
      the exam and an increased diagnostic value. Additionally, new equipment including
      a perfusion device with single use sets as well as a special contrast agent for
      post-mortem investigations has been created. Using this technique, angio-CT
      permits to detect of the source of haemorrhages, vascular malformations,
      arteriosclerotic lesions as well as vascular occlusions and to visualize the
      vascular anatomy exactly.

PMID- 21899219
TI  - [Positional asphyxia, a cause of death insufficiently known].
AB  - Positional asphyxia (AP) is a fatal condition arising because of the adoption of
      particular body positions, causing mechanical interference. Consequences are
      important alveolar hypoventilation and cardiac hyperexcitability due to
      respiratory acidosis in combination with extensive liberation of catecholamine
      occurring in attracted individuals sustaining physical restrain. This syndrome
      can occur in various circumstances and is mostly observed in situations with
      physical restraint and in combination with excited delirium (ED). The diagnosis
      is essentially based on three criteria: body position obstructing normal
      breathable air exchange, impossibility to move to another position and exclusion
      of other causes of natural or violent death.

PMID- 21899220
TI  - [Screening for lung cancer in smokers].

PMID- 21899221
TI  - [Genetic entertainment and coffee grounds].

PMID- 21899222
TI  - [The daughter of Mrs. Z].

PMID- 21899223
TI  - A message from the Editor-in-Chief.

PMID- 21899224
TI  - Access with evidence development: an approach to introducing promising new
      technologies into healthcare.
AB  - The rapid development of new health technologies for which there is limited, but
      promising, evidence has resulted in a daunting challenge - to provide care that
      meets population health needs and optimizes patient outcomes, demonstrates an
      efficient use of healthcare resources, and upholds basic principles of equity,
      access, and choice. In this paper, we introduce 'Access with Evidence
      Development' as a possible mechanism for addressing this challenge and discuss
      its application to the "Zamboni procedure" for Multiple Sclerosis.

PMID- 21899225
TI  - Patient choice systems and waiting times for scheduled services.
AB  - Access to scheduled healthcare is a continuing challenge. A synthesis of the
      international literature was conducted to examine the potential of patient choice
      systems to reduce waiting times in Canada. A multitude of factors appear to
      influence the actions and outcomes of patients, providers, and systems. For
      choice systems to be effective, there must be uptake, which requires incentives
      and supports. Choice should be considered as but one element of a comprehensive
      waiting time management strategy.

PMID- 21899226
TI  - The restructuring of institutional long-term care in St. John's: impact of supply
      induced demand on planning.
AB  - Restructuring of institutional long-term care was undertaken using predictions of
      future bed need with assumptions made on incidence rates of clients defined by
      type of disability, survival, and demographic changes. Recent substantial
      increase in the population rate of clients seeking placement across all degrees
      of disability, coincident with new facilities for those with modest disability,
      occurred. Consequently, more appropriate housing and supervised care beds, and
      more limited downsizing of nursing homes will be required.

PMID- 21899227
TI  - The Top 30 Rising Stars Program: an inter-organizational approach to leadership
      succession planning.
AB  - An effective leadership development program is an organizational investment that
      advances individual performance while strengthening organizational capabilities.
      The Top 30 Rising Stars Program is a leadership succession program designed to
      enable leadership capacity building within and across organizations. Key
      components of the program include formal learning, stretch opportunities, and
      mentorship. Evaluation results reveal high participant satisfaction and an
      increase in reported self-confidence in their ability to assume a formal
      leadership position.

PMID- 21899228
TI  - Capacity building in residential care.
AB  - A retrospective analysis of how the Dementia Care Program (DCP) contributed to
      capacity building at The Lodge at Broadmead (2004-2009) was conducted in 2010.
      Results showed facility-wide enhancements in (1) information capital, because of
      educational workshops and other forms of interactive learning for all staff, and
      (2) social capital, because of evaluation and information-sharing. It was
      concluded that the DCP increased staff's capacity to deliver best practice
      dementia care.

PMID- 21899229
TI  - Client satisfaction in support of service planning within a regulatory framework:
      experience of a research hospital.
AB  - Research Operations at UHN provide services to a large, complex client research
      community with varying needs. This requires complex coordination and continual
      refining of service and resource targets to meet client, government and external
      stakeholder requirements. The UHN Research Operations model focuses on six key
      enablers: client education, service team expertise, direct communication, process
      improvement, quality assurance, and, systems and tools. Service departments that
      have deployed these enablers experience improved client satisfaction.

PMID- 21899230
TI  - Ethical leadership in action.

PMID- 21899231
TI  - Evidence-based practice for staff nurses.
AB  - BACKGROUND: Barriers to the involvement of staff nurses in evidence-based
      practice include time commitments, staffing challenges, and limited experience in
      identifying evidence. METHODS: A 1-day, hands-on course focused on small,
      achievable, evidence-based practice projects; follow-up after the course by a
      project director; and commitment to implementation of participants' projects by
      management. Faculty included a librarian who helped with computer searches and a
      quality assurance representative to facilitate availability of institutional data
      for project evaluation. RESULTS: Nine courses held over a 3-year period involved
      79 home institution nurses and 76 community nurses. Course evaluations were
      overwhelmingly positive. Completed projects were displayed on participants' units
      and circulated throughout the institution. The courses are continuing as part of
      the regular annual nursing education calendar. CONCLUSION: Streamlined approaches
      to teaching evidence-based practice can be used to involve staff nurses and raise
      awareness of evidence-based practice across nursing. Key positive findings
      include achievable projects, provisions for follow-up, and management support.

PMID- 21899232
TI  - Evaluating the effectiveness of a clinical preceptorship program for registered
      nurses in jordan.
AB  - PURPOSE: The authors implemented and evaluated a preceptor training program to
      prepare registered nurses to become preceptors and to establish a nursing
      preceptor training program to promote knowledge of preceptorship among Jordanian
      nurses. METHODS: A true experimental design was used. The sample consisted of 68
      registered nurses recruited randomly from governmental, private, and university
      hospitals. A sociodemographic data form and a questionnaire on nurses' knowledge
      about preceptorship were developed for self-administration. RESULTS: The study
      results showed that the difference between the experimental (n = 30, M = 33/41,
      SD = 4.5) and control (n = 38, M = 26/41, SD = 4.6) groups after implementation
      of the preceptorship program was statistically significant (t = 5.5, df = 66, p =
      .000). CONCLUSION: The preceptorship program showed significant improvement in
      participants' knowledge of clinical teaching.

PMID- 21899233
TI  - Radiologic case study. Musculoskeletal actinomycosis.

PMID- 21899234
TI  - Current concepts in joint replacement.

PMID- 21899235
TI  - The use of the lotus position during spica cast application for the treatment of
      developmental dysplasia of the hip: a technical note.
AB  - Closed reduction and application of a spica cast is a standard treatment in
      children younger than 18 months. Proper abduction and flexion is crucial during
      cast application. The surgeon, who usually stands holding the lower limbs, often
      finds this position cumbersome and difficult to control limb position. During the
      past 6 years, we have used the lotus (crossed legs) position for the surgeon to
      achieve better control on hip flexion and abduction, therefore minimizing
      possible complications such as osteonecrosis of the femoral head.

PMID- 21899236
TI  - Flexor tendon injuries.

PMID- 21899237
TI  - Drug shortages: causes and cautions.
AB  - Drug shortages have increasingly been a problem for pharmacists and clinicians
      over the past decade. Clinicians need to be aware of the various causes of drug
      shortages and the issues that may arise as a result, particularly as they relate
      to medication safety. Numerous resources and strategies are available to mitigate
      the effects of drug shortages, and clinicians should work with their health care
      team and the patient to determine the best option when faced with a drug shortage
      that affects patient care.

PMID- 21899238
TI  - Management of talar neck fractures.
AB  - Talar neck fractures are usually the result of high-energy trauma. It remains
      controversial whether talar neck fractures require emergent treatment. Most
      surgeons recommend the use of dual surgical approaches, anteromedial and
      anterolateral, to allow accurate visualization and anatomic reduction. It is
      important to carefully preserve any remaining talar blood supply. Obtaining
      satisfactory clinical results, while avoiding complications, presents a unique
      challenge in the treatment of talar neck fractures. Common complications include
      posttraumatic arthritis, avascular necrosis, malunion, and nonunion.

PMID- 21899240
TI  - Advances in astigmatism management.

PMID- 21899241
TI  - Secondary ectasia due to forceps injury at childbirth: management with combined
      topography-guided partial PRK and collagen cross-linking (Athens Protocol) and
      subsequent phakic IOL implantation.

PMID- 21899242
TI  - Vincenz Fukala (1847-1911) and the early history of clear-lens surgery in high
      myopia.

PMID- 21899243
TI  - Analysis of the relationship between drusen size and drusen area in eyes with age
      related macular degeneration.
AB  - BACKGROUND AND OBJECTIVE: To examine the relationship between drusen counts and
      drusen area in eyes with age-related macular degeneration, and to correlate
      drusen areas between fellow eyes. PATIENTS AND METHODS: Digital images from 378
      patients (756 eyes) were analyzed using a validated drusen detection algorithm.
      Total drusen area and the number of drusen of various sizes (small: < 62 microns,
      intermediate: 63-124 microns, large: 125-249 microns, etc) were recorded for the
      central 1,000- and 3,000-micron diameter macular regions. Correlations were
      assessed using structural equation models. RESULTS: For the 1,000-micron region,
      the number of intermediate drusen was more highly correlated to total drusen area
      than the number of large drusen (R = 0.91 vs 0.82); this difference was
      statistically significant. The correlation coefficients for drusen area between
      fellow eyes was 0.73. CONCLUSION: The number of large drusen does not correlate
      better with total drusen area than drusen of other sizes. The number of large
      drusen is not necessarily a good surrogate for total drusen area.

PMID- 21899245
TI  - Comparison of non-contact methods for the measurement of central corneal
      thickness.
AB  - BACKGROUND AND OBJECTIVE: This study examined the repeatability of and agreements
      between central corneal thickness measurements obtained by four different non
      contact pachymetry devices. PATIENTS AND METHODS: Seventy-eight eyes of 39
      subjects were included. Central corneal thickness of each eye was measured by
      Visante optical coherence tomography (OCT) (Carl Zeiss Meditec Inc., Dublin, CA),
      Pentacam (Oculus Optikgerate GmbH, Wetzlar, Germany), Orbscan IIz topography
      (Bausch & Lomb Surgical Inc., San Dimas, CA), and slit-lamp OCT (SL-OCT)
      (Heidelberg Engineering GmbH, Heidelberg, Germany). Inter-device agreements and
      correlations and repeatability of each device were examined. RESULTS: All
      measurement methods correlated well with each other with a correlation
      coefficient greater than 0.90 and P value of less than .001 for all comparisons.
      However, Pentacam overestimated central corneal thickness: 546.7 +/- 38.2, 535.5
      +/- 42.7, 531.7 +/- 37.6, and 531.2 +/- 36.0 MUm for Pentacam, Orbscan IIz,
      Visante OCT, and SL-OCT, respectively (P < .001 for all comparisons versus
      Pentacam). Despite good correlation, magnitude of differences was high and this
      bias was proportional (ie, not constant across a range of corneal thickness
      values) for the following pairs: Orbscan versus Visante OCT, Orbscan versus SL
      OCT, and Orbscan versus Pentacam (P < .001 for all comparisons). CONCLUSION:
      Although measurements obtained by various non-contact methods correlate well,
      numerical agreement of the results may not be sufficient for their
      interchangeable use in clinical practice.

PMID- 21899244
TI  - Corneal endothelial cell changes after Ahmed valve and Molteno glaucoma implants.
AB  - BACKGROUND AND OBJECTIVE: Changes in corneal endothelial cell (CEC) indices 24
      months after Ahmed valve (New World Medical, Inc., Rancho Cucamonga, CA) and
      single-plate Molteno implants (Molteno Ophthalmic Limited, Dunedin, New Zealand)
      were evaluated. PATIENTS AND METHODS: This cohort included Ahmed valve (29 eyes)
      or single-plate Molteno (28 eyes) implants. Preoperative and postoperative
      central CEC indices were compared. Main outcome measure was endothelial cell
      count. RESULTS: Twenty-four months postoperatively, no difference in visual
      acuity improvement or decrease in antiglaucoma medications was observed between
      groups. The Molteno group showed better postoperative intraocular pressure
      control (P < .001). An 11.52% (Ahmed) and 12.37% (Molteno) reduction in CEC
      density (cells/mm(2)) and 3.78 (Ahmed) and 2.48 (Molteno) increase in CEC area
      (mm(2)) was observed, but no significant between-group difference in CEC density
      and area or corneal thickness. CONCLUSION: Twenty-four months after Ahmed valve
      or Molteno implant, statistically significant quantitative (cell density) and
      minor qualitative (cell area) changes in central CEC were observed. Both groups
      appeared to have similar CEC damage.

PMID- 21899246
TI  - Between-grader repeatability of tear meniscus measurements using Fourier-domain
      OCT in patients with dry eye.
AB  - BACKGROUND AND OBJECTIVE: To examine the between-grader repeatability of height,
      depth, and cross-sectional area measurements of the lower tear meniscus, using a
      Fourier-domain optical coherence tomography (OCT) system. PATIENTS AND METHODS: A
      total of 16 patients with dry eye had the lower tear meniscus of the right eye
      imaged twice in rapid succession. The tear meniscus height, depth, and cross
      sectional area were measured by two masked graders using computer calipers. The
      between-grader variability, calculated using the pooled coefficient of variation
      (CV%), assessed the repeatability of the measurements. RESULTS: The between
      grader CV% was 12.1%, 15.7%, and 19.5% for height, depth, and area, respectively.
      The between-image variability was 17.1%, 13.4%, and 35.4% for height, depth, and
      area, respectively. The overall intraclass correlation was 99%. There was no
      systematic bias between the two graders. CONCLUSION: Fourier-domain OCT
      demonstrates good between-grader and between-image repeatability in measuring the
      height, depth, and cross-sectional area of the tear meniscus in patients with dry
      eye. Measurement variability was primarily due to the difference between images
      rather than graders.

PMID- 21899247
TI  - Comparison of complication rates of porous anophthalmic orbital implants.
AB  - BACKGROUND AND OBJECTIVE: Porous anophthalmic orbital implants are used widely.
      This study evaluates risk factors for porous anophthalmic orbital implant
      complications and compares complication rates of hydroxyapatite, porous
      polyethylene, and polyglactin mesh-wrapped aluminum oxide implants. PATIENTS AND
      METHODS: The records of 105 patients (110 eyes) who received porous anophthalmic
      orbital implants for any indication were reviewed retrospectively. Complications
      were recorded and correlated with potential risk factors, including implant
      material. All patient records were de-identified to protect privacy. RESULTS:
      Porous polyethylene and aluminum oxide implants were associated with higher
      exposure rates (porous polyethylene: odds ratio 6.1 [1.29, 29.1]; aluminum oxide:
      odds ratio 6.0 [1.58, 23.1]; P = .004) and higher overall complication rates
      compared to hydroxyapatite implants. CONCLUSION: Implant material may be a risk
      factor for several anophthalmic clinical outcomes.

PMID- 21899248
TI  - Spectral-domain optical coherence tomography features of mild and severe acute
      solar retinopathy.
AB  - Photochemical/thermal retinal damage that results from unprotected solar eclipse
      viewing has vague presentations and sometimes misleading diagnosis, especially in
      cases with unclear history. Spectral-domain optical coherence tomography (SD-OCT)
      is a non-invasive imaging technique useful in differential diagnosis that can
      reveal characteristic foveal alterations in solar retinopathy to an unprecedented
      quasi histologic level. The authors present high-resolution SD-OCT findings
      correlated with clinical findings in three eyes of two cases with acute solar
      retinopathy. SD-OCT can precisely define the site and extent of damage in acute
      solar retinopathy. In mild forms, damage may be limited to the outer retina with
      inner segment/outer segment disruption. In severe forms, full thickness macular
      damage may be seen. Advances in retinal imaging have improved our ability to
      provide precise correlation with clinical presentation and prognosis.

PMID- 21899249
TI  - Intravitreal ganciclovir and dexamethasone as adjunctive therapy in the
      management of acute retinal necrosis caused by varicella zoster virus.
AB  - A 40-year-old man presented with a visual acuity of 20/400 in his right eye due
      to acute retinal necrosis involving two inferior quadrants. Diagnostic vitreous
      tap was positive for varicella zoster virus and he received intravitreal
      injections of ganciclovir (2 mg/0.1 mL) and dexamethasone (400 mcg/0.1 mL). Oral
      prednisone was added on day 3 and tapered over 3 months. Lesions showed
      pigmentation around day 5 and healed by day 9. He developed vitreous hemorrhage 5
      months after presentation and was treated with 25-gauge pars plana vitrectomy
      combined with panretinal photocoagulation. Final follow-up at 7 months showed a
      visual acuity of 20/30, mild optic atrophy, narrow arteries, healed retinal
      lesions, and good panretinal photocoagulation. Intravitreal injections of
      dexamethasone and ganciclovir may have a role as an adjunctive therapy in the
      management of patients with acute retinal necrosis, particularly those caused by
      varicella zoster virus.

PMID- 21899250
TI  - Retinopathy associated with pegylated interferon and ribavirin causing permanent
      visual impairment in a patient with chronic hepatitis C.
AB  - Retinopathy associated with pegylated interferon and ribavirin is a known
      complication of this therapy, and is typically bilateral and asymptomatic. Few
      patients complain of visual disturbance, and only rarely is there permanent
      visual impairment after the retinopathy resolves. A 65-year-old man presented
      with bilateral reduced visual acuity. Treatment with pegylated interferon and
      ribavirin was initiated 12 weeks prior due to chronic hepatitis virus C. On
      examination, multiple cotton-wool spots were noticed bilaterally, and visual
      field testing demonstrated decreased sensitivity. Treatment was stopped and the
      retinopathy was followed up for 4 months by ophthalmic examination and high
      resolution optical coherence tomography. The cotton-wool spots resolved and high
      resolution optical coherence tomography demonstrated restoration of normal
      retinal configuration. Visual acuity and visual field testing improved over 4
      months, but did not return to their baseline values. This is a rare case of
      permanent visual impairment caused by retinopathy associated with pegylated
      interferon and ribavirin.

PMID- 21899251
TI  - Fluorescence correlation spectroscopy: an efficient tool for measuring size, size
      distribution and polydispersity of microemulsion droplets in solution.
AB  - Fluorescence correlation spectroscopy (FCS) is an ideal tool for measuring
      molecular diffusion and size under extremely dilute conditions. However, the
      power of FCS has not been utilized to its best to measure diffusion and size
      parameters of complex chemical systems. Here, we apply FCS to measure the size,
      and, most importantly, the size distribution and polydispersity of a
      supramolecular nanostructure (i.e., microemulsion droplets, MEDs) in dilute
      solution. It is shown how the refractive index mismatch of a solution can be
      corrected in FCS to obtain accurate size parameters of particles, bypassing the
      optical matching problem of light scattering techniques that are used often for
      particle-size measurements. We studied the MEDs of 13 different W(0) values from
      2 to 50 prepared in a ternary mixture of water, sodium bis(2-ethylhexyl)
      sulfosuccinate (AOT), and isooctane, with sulforhodamine-B as a fluorescent
      marker. We find that, near the optical matching point of MEDs, the dynamic light
      scattering (DLS) measurements underestimate the droplet sizes while FCS estimates
      the accurate ones. A Gaussian distribution model (GDM) and a maximum-entropy
      based FCS data fitting model (MEMFCS) are used to analyze the fluorescence
      correlation curves that unfold Gaussian-type size distributions of MEDs in
      solution. We find the droplet size varies linearly with W(0) up to ~20, but
      beyond this W(0) value, the size variation deviates from this linearity. To
      explain nonlinear variation of droplet size for W(0) values beyond ~20, we invoke
      a model (the coated-droplet model) that incorporates the size polydispersity of
      the droplets.

PMID- 21899252
TI  - Computational study on the reaction pathway of alpha-bromoacetophenones with
      hydroxide ion: possible path bifurcation in the addition/substitution mechanism.
AB  - The reaction of an alpha-haloketone with a nucleophile has three reaction
      channels: carbonyl addition, direct substitution, and proton abstraction. DFT
      calculations for the reaction of PhCOCH(2)Br with OH(-) showed that there exists
      an addition/substitution TS on the potential energy surface, in which OH(-)
      interacts with both the alpha- and carbonyl carbons. The intrinsic reaction
      coordinate calculations revealed that the TS serves as the TS for direct
      substitution for XC(6)H(4)COCH(2)Br with an electron-donating X or a X less
      electron-withdrawing than m-Cl, whereas the TS serves as the TS for carbonyl
      addition for derivatives with a X more electron-withdrawing than m-CF(3).
      Trajectory calculations starting at respective TS indicated that the single TS
      can serve for the two mechanisms, substitution and addition, through path
      bifurcation after the TS for borderline substrates. The reaction is the first
      example of dynamic path bifurcation for fundamental reaction types of carbonyl
      addition and substitution.

PMID- 21899253
TI  - Unprecedented binary Cu(I)/Cu(II) catalyzed one-pot, three-component synthesis
      and evaluation of luminescent property of 2-amino-3-iminoethenylidene-2
      indolones: a new class of merocyanine dye analogues.
AB  - A facile and efficient binary Cu(I)/Cu(II) catalyzed one-pot, three-component
      synthesis of 2-amino-3-iminoethenylidene-2-indolones in excellent yield has been
      achieved. Remarkably, these newly synthesized, stable merocyanine dye analogues
      showed strong luminescence in the blue region with large Stokes shifts.

PMID- 21899254
TI  - Zinc tetrafluoroborate hydrate as a mild catalyst for epoxide ring opening with
      amines: scope and limitations of metal tetrafluoroborates and applications in the
      synthesis of antihypertensive drugs (RS)/(R)/(S)-metoprolols.
AB  - The scope and limitations of metal tetrafluoroborates have been studied for
      epoxide ring-opening reaction with amines, and Zn(BF(4))(2).xH(2)O has been found
      to be a mild and efficient catalyst affording high yields under solvent-free
      conditions at rt with excellent chemo-, regio-, and stereoselectivities. The
      catalytic efficiency followed the order Zn(BF(4))(2).xH(2)O ? Cu(BF(4))(2).xH(2)O
      > Co(BF(4))(2).6H(2)O ? Fe(BF(4))(2).6H(2)O > LiBF(4) for reactions with
      cyclohexene oxide and Zn(BF(4))(2).xH(2)O ? Co(BF(4))(2).6H(2)O ?
      Fe(BF(4))(2).6H(2)O > Cu(BF(4))(2).xH(2)O for stilbene oxide, but AgBF(4) was
      ineffective. For reaction of styrene oxide with aniline, the metal
      tetrafluoroborates exhibited comparable regioselectivity (1:99-7:93) with
      preferential reaction at the benzylic carbon of the epoxide ring. A reversal of
      regioselectivity (91:1-69:31) in favor of the reaction at the terminal carbon of
      the epoxide ring was observed for reaction with morpholine. The regioselectivity
      was dependent on the electronic and steric factors of the epoxide and the pK(a)
      of the amine and independent of amine nucleophilicity. The role of the metal
      tetrafluoroborates is envisaged as "electrophile nucleophile dual activation"
      through cooperativity of coordination, charge-charge interaction, and hydrogen
      bond formation that rationalizes the catalytic efficiency, substrate reactivity,
      and regioselectivity. The methodology was used for synthesis of cardiovascular
      drug metoprolol as racemic and enriched enantiomeric forms.

PMID- 21899255
TI  - Predicting the age and type of tuocha tea by fourier transform infrared
      spectroscopy and chemometric data analysis.
AB  - Fourier transform infrared (FTIR) spectroscopy combined with chemometric
      multivariate methods was proposed to discriminate the type (unfermented and
      fermented) and predict the age of tuocha tea. Transmittance FTIR spectra ranging
      from 400 to 4000 cm(-1) of 80 fermented and 98 unfermented tea samples from
      Yunnan province of China were measured. Sample preparation involved finely
      grinding tea samples and formation of thin KBr disks (under 120 kg/cm(2) for 5
      min). For data analysis, partial least-squares (PLS) discriminant analysis
      (PLSDA) was applied to discriminate unfermented and fermented teas. The
      sensitivity and specificity of PLSDA with first-derivative spectra were 93 and
      96%, respectively. Multivariate calibration models were developed to predict the
      age of fermented and unfermented teas. Different options of data preprocessing
      and calibration models were investigated. Whereas linear PLS based on standard
      normal variate (SNV) spectra was adequate for modeling the age of unfermented tea
      samples (RMSEP = 1.47 months), a nonlinear back-propagation-artificial neutral
      network was required for calibrating the age of fermented tea (RMSEP = 1.67
      months with second-derivative spectra). For type discrimination and calibration
      of tea age, SNV and derivative preprocessing played an important role in reducing
      the spectral variations caused by scattering effects and baseline shifts.

PMID- 21899257
TI  - Si-based flexible memristive systems constructed using top-down methods.
AB  - Si-based memristive systems consisting of Ag, amorphous Si, and heavily doped p
      type Si nanowires were successfully constructed on plastic substrates through top
      down methods, including the crystallographic wet etching of Si wafers, transfer
      onto plastic substrates, and thin film patterning. The memristive systems showed
      excellent memory characteristics and flexibility, such as intrinsic hysteric and
      rectifying behaviors, on/off resistance ratios of >1 * 10(5), and durability for
      up to 1000 bending cycles. The correlations between the Ag-filament-related
      nanostructures formed in amorphous Si and the resistance-switching behaviors were
      carefully examined with the tunneling current model, transmission electron
      microscopy, and secondary ion mass spectroscopy to explore the switching
      mechanism. Our study suggests the promising potential of the Si-based memristive
      systems for the development of next-generation flexible nonvolatile memory.

PMID- 21899256
TI  - Hexose transporter GLUT1 harbors several distinct regulatory binding sites for
      flavones and tyrphostins.
AB  - The facilitative hexose transporter GLUT1 activity is blocked by tyrosine kinase
      inhibitors that include natural products such as flavones and isoflavones and
      synthetic compounds such as tyrphostins, molecules that are structurally
      unrelated to the transported substrates [Vera, et al. (2001) Biochemistry, 40,
      777-790]. Here we analyzed the interaction of GLUT1 with quercetin (a flavone),
      genistein (an isoflavone), and tyrphostin A47 and B46 to evaluate if they share
      one common or have several binding sites on the protein. Kinetic assays showed
      that genistein, quercetin, and tyrphostin B46 behave as competitive inhibitors of
      equilibrium exchange and zero-trans uptake transport and noncompetitive
      inhibitors of net sugar exit out of human red cells, suggesting that they
      interact with the external surface of the GLUT1 molecule. In contrast, tyrphostin
      A47 was a competitive inhibitor of equilibrium exchange and zero-trans exit
      transport and a noncompetitive inhibitor of net sugar entry into red cells,
      suggesting that it interacts with the cytoplasmic surface of the transporter.
      Genistein protected GLUT1 against iodide-elicited fluorescence quenching and also
      decreased the affinity of d-glucose for its external binding site, while
      quercetin and tyrphostins B46 and A47 promoted fluorescence quenching and did not
      affect the external d-glucose binding site. These findings are explained by a
      carrier that presents at least three binding sites for tyrosine kinase
      inhibitors, in which (i) genistein interacts with the transporter in a
      conformation that binds glucose on the external surface (outward-facing
      conformation), in a site which overlaps with the external binding site for d
      glucose, (ii) quercetin and tyrphostin B46 interact with the GLUT1 conformation
      which binds glucose by the internal side of the membrane (inward-facing
      conformation), but to a site accessible from the external surface of the protein,
      and (iii) the binding site for tyrphostin A47 is accessible from the inner
      surface of GLUT1 by binding to the inward-facing conformation of the transporter.
      These data provide groundwork for a molecular understanding of how the tyrosine
      kinase inhibitors directly affect glucose transport in animal cells.

PMID- 21899259
TI  - A criterion for anomalous melting in systems with isotropic interactions.
AB  - The relationship between anomalous (re-entrant) melting and the features of the
      repulsive part of the intermolecular potential is studied in one-component
      systems with radially symmetric interactions. By making use of the Lennard-Jones
      Devonshire cell model, we derive a single-phase criterion for the occurrence of a
      temperature maximum in the melting line. The criterion is tested against
      numerical simulation results for a number of isotropic interaction models.

PMID- 21899258
TI  - Direct, metal-free amination of heterocyclic amides/ureas with NH-heterocycles
      and N-substituted anilines in POCl3.
AB  - A POCl(3)-mediated, direct amination reaction of heterocyclic amides/ureas with
      NH-heterocycles or N-substituted anilines is described. Compared to the existing
      methods, this operationally simple protocol provides unique reactivity and
      functional group compatibility because of the metal-free, acidic reaction
      conditions. The yields are generally excellent.

PMID- 21899260
TI  - Molecular dynamics simulations of the structural and thermodynamic properties of
      imidazolium-based ionic liquid mixtures.
AB  - In this work, extensive molecular dynamics simulations of mixtures of alcohols of
      several chain lengths (methanol and ethanol) with the ionic liquids (ILs)
      composed of the cation 1-hexyl-3-methylimidazolium and several anions of
      different hydrophobicity degrees (Cl(-), BF(4)(-), PF(6)(-)) are reported. We
      analyze the influence of the nature of the anion, the length of the molecular
      chain of the alcohol, and the alcohol concentration on the thermodynamic and
      structural properties of the mixtures. Densities, excess molar volumes, total and
      partial radial distribution functions, coordination numbers, and hydrogen bond
      degrees are reported and analyzed for mixtures of the ILs with methanol and
      ethanol. The aggregation process is shown to be highly dependent on the nature of
      the anion and the size of the alcohol, since alcohol molecules tend to interact
      predominantly with the anionic part of the IL, especially in mixtures of the
      halogenated IL with methanol. Particularly, our results suggest that the
      formation of an apolar network similar to that previously reported in mixtures of
      ILs with water does not take place in mixtures with alcohol when the chloride
      anion is present, the alcohol molecules being instead homogeneously distributed
      in the polar network of IL. Moreover, the alcohol clusters formed in mixtures of
      [HMIM][PF(6)] with alcohol were found to have a smaller size than in mixtures
      with water. Additionally, we provide a semiquantitative analysis of the
      dependence of the hydrogen bonding degree of the mixtures on the alcohol
      concentration.

PMID- 21899261
TI  - The E. coli monothiol glutaredoxin GrxD forms homodimeric and heterodimeric FeS
      cluster containing complexes.
AB  - Monothiol glutaredoxins (mono-Grx) represent a highly evolutionarily conserved
      class of proteins present in organisms ranging from prokaryotes to humans. Mono
      Grxs have been implicated in iron sulfur (FeS) cluster biosynthesis as potential
      scaffold proteins and in iron homeostasis via an FeS-containing complex with
      Fra2p (homologue of E. coli BolA) in yeast and are linked to signal transduction
      in mammalian systems. However, the function of the mono-Grx in prokaryotes and
      the nature of an interaction with BolA-like proteins have not been established.
      Recent genome-wide screens for E. coli genetic interactions reported the
      synthetic lethality (combination of mutations leading to cell death; mutation of
      only one of these genes does not) of a grxD mutation when combined with strains
      defective in FeS cluster biosynthesis (isc operon) functions [Butland, G., et al.
      (2008) Nature Methods 5, 789-795]. These data connected the only E. coli mono
      Grx, GrxD to a potential role in FeS cluster biosynthesis. We investigated GrxD
      to uncover the molecular basis of this synthetic lethality and observed that GrxD
      can form FeS-bound homodimeric and BolA containing heterodimeric complexes. These
      complexes display substantially different spectroscopic and functional
      properties, including the ability to act as scaffold proteins for intact FeS
      cluster transfer to the model [2Fe-2S] acceptor protein E. coli apo-ferredoxin
      (Fdx), with the homodimer being significantly more efficient. In this work, we
      functionally dissect the potential cellular roles of GrxD as a component of both
      homodimeric and heterodimeric complexes to ultimately uncover if either of these
      complexes performs functions linked to FeS cluster biosynthesis.

PMID- 21899262
TI  - Complexity generation in fungal peptidyl alkaloid biosynthesis: oxidation of
      fumiquinazoline A to the heptacyclic hemiaminal fumiquinazoline C by the
      flavoenzyme Af12070 from Aspergillus fumigatus.
AB  - The human pathogen Aspergillus fumigatus makes a series of fumiquinazoline (FQ)
      peptidyl alkaloids of increasing scaffold complexity using L-Trp, 2 equiv of L
      Ala, and the non-proteinogenic amino acid anthranilate as building blocks. The FQ
      gene cluster encodes two non-ribosomal peptide synthetases (NRPS) and two
      flavoproteins. The trimodular NRPS Af12080 assembles FQF (the first level of
      complexity) while the next two enzymes, Af12060 and Af12050, act in tandem in an
      oxidative annulation sequence to couple alanine to the indole side chain of FQF
      to yield the imidazolindolone-containing FQA. In this study we show that the
      fourth enzyme, the monocovalent flavoprotein Af12070, introduces a third layer of
      scaffold complexity by converting FQA to the spirohemiaminal FQC, presumably by
      catalyzing the formation of a transient imine within the pyrazinone ring (and
      therefore acting in an unprecedented manner as an FAD-dependent amide oxidase).
      FQC subsequently converts nonenzymatically to the known cyclic aminal FQD. We
      also investigated the effect of substrate structure on Af12070 activity and
      subsequent cyclization with a variety of FQA analogues, including an FQA
      diastereomer (2'-epi-FQA), which is an intermediate in the fungal biosynthesis of
      the tremorgenic tryptoquialanine. 2'-epi-FQA is processed by Af12070 to epi-FQD,
      not epi-FQC, illustrating that the delicate balance in product cyclization
      regiochemistry can be perturbed by a remote stereochemical center.

PMID- 21899263
TI  - Hydrogen/deuterium exchange and electron-transfer dissociation mass spectrometry
      determine the interface and dynamics of apolipoprotein E oligomerization.
AB  - Apolipoprotein E, a 34 kDa protein, plays a key role in triglyceride and
      cholesterol metabolism. Of the three common isoforms (ApoE2, -3, and -4), only
      ApoE4 is a risk factor for Alzheimer's disease. All three isoforms of wild-type
      ApoE self-associate to form oligomers, a process that may have functional
      consequences. Although the C-terminal domain, residues 216-299, of ApoE is
      believed to mediate self-association, the specific residues involved in this
      process are not known. Here we report the use of hydrogen/deuterium exchange
      (H/DX) coupled with enzymatic digestion to identify those regions in the sequence
      of full-length apoE involved in oligomerization. For this determination, we
      compared the results of H/DX of the wild-type proteins and those of monomeric
      forms obtained by modifying four residues in the C-terminal domain. The three
      wild-type and mutant isoforms show similar structures based on their similar H/DX
      kinetics and extents of exchange. Regions of the C-terminus (residues 230-270) of
      the ApoE isoforms show significant differences of deuterium uptake between
      oligomeric and monomeric forms, confirming that oligomerization occurs at these
      regions. To achieve single amino acid resolution, we examined the extents of H/DX
      by using electron transfer dissociation (ETD) fragmentation of peptides
      representing selected regions of both the monomeric and the oligomeric forms of
      ApoE4. From these experiments, we could identify the specific residues involved
      in ApoE oligomerization. In addition, our results verify that ApoE4 is composed
      of a compact structure at its N-terminal domain. Regions of C-terminal domain,
      however, appear to lack defined structure.

PMID- 21899265
TI  - Honeycomb-patterned film segregated with phenylboronic acid for glucose sensing.
AB  - Phenylboronic acid (PBA)-functionalized materials have attracted considerable
      attention because of their potential applications in many fields. In this paper,
      we report a PBA-segregated honeycomb-patterned porous film (HPPF) for glucose
      sensing. Polystyrene-block-poly(acrylic acid-co-acrylamidophenylboronic acid)
      with different contents of PBA pendants was synthesized via atom transfer radical
      polymerization (ATRP) followed by a coupling reaction. PBA-functionalized HPPFs
      were then fabricated by the breath figure method. Results indicate that the
      composition of the copolymers and the relative humidity play key roles in pore
      size and regularity of the films. Using Alizarin Red S (ARS) that does not emit
      fluorescence itself as a fluorescent probe, it is confirmed that PBA pendants are
      mainly distributed at the pore wall, instead of at the outer surface of HPPFs.
      This distribution is caused by the segregation of hydrophilic PBA-blocks toward
      the condensed water droplets, which act as templates for the pore formation.
      Quartz crystal microbalance results demonstrate that the PBA-functionalized HPPFs
      show high sensitivity in glucose sensing, which is owing to the segregation of
      PBA pendants at the pore wall as well as the large specific surface area of the
      porous films.

PMID- 21899264
TI  - Nitrocapsanthin and nitrofucoxanthin, respective products of capsanthin and
      fucoxanthin reaction with peroxynitrite.
AB  - The in vitro reactivity of capsanthin (1) and fucoxanthin (2) with peroxynitrite
      was investigated, and the reaction products produced by scavenging with
      peroxynitrite were analyzed. (14'Z)-Nitrocapsanthin (3) and 12-nitrocapsanthin
      (4) were isolated from the products of the reaction of capsanthin with
      peroxynitrite. Similarly, (14Z)-15-nitrofucoxanthin (5), (11Z)-11
      nitrofucoxanthin (6), and (14Z,9'Z)-15-nitrofucoxanthin (7) were obtained from
      the reaction of peroxynitrite reaction with fucoxanthin. Capsanthin and
      fucoxanthin inhibited the nitration of tyrosine by peroxynitrite. Furthermore,
      nitrocapsanthins (3 and 4) and nitrofucoxanthins (5 and 6) exhibited an
      inhibitory effect on Epstein-Barr virus early antigen activation in Raji cells
      and an antiproliferative effect on human pancreatic carcinoma. Moreover,
      nitrocapsanthins (3 and 4) inhibited carcinogensis of mouse skin tumors initiated
      by 7,12-dimethylbenz[a]anthracene (DMBN).

PMID- 21899266
TI  - The cephalostatins. 21. Synthesis of bis-steroidal pyrazine rhamnosides (1).
AB  - The synthesis of bis-steroidal pyrazines derived from 3-oxo-11,21-dihydroxypregna
      4,17(20)-diene (4) and glycosylation of a D-ring side chain with alpha-L-rhamnose
      have been summarized. Rearrangement of steroidal pyrazine 10 to 14 was found to
      occur with boron triflouride etherate. Glycosylation of pyrazine 10 using 2,3,4
      tri-O-acetyl-alpha-L-rhamnose iodide led to 1,2-orthoester-alpha-L-rhamnose
      pyrazine 17b. By use of a persilylated alpha-L-rhamnose iodide as donor,
      formation of the orthoester was avoided. Bis-steroidal pyrazine 10 and
      rhamnosides 17b and 21c were found to significantly inhibit cancer cell growth in
      a murine and human cancer cell line panel. Pyrazine 9 inhibited growth of the
      nosocomial pathogen Enterococcus faecalis.

PMID- 21899267
TI  - Antibacterial acylphloroglucinols from Hypericum olympicum.
AB  - New antibacterial acylphloroglucinols (1-5) were isolated and characterized from
      the aerial parts of the plant Hypericum olympicum L. cf. uniflorum. The
      structures of these compounds were confirmed by extensive 1D- and 2D-NMR
      experiments to be 4,6-dihydroxy-2-O-(3",7"-dimethyl-2",6"-octadienyl)-1-(2'
      methylbutanoyl)benzene (1), 4,6-dihydroxy-2-O-(7"-hydroxy-3",7"-dimethyl-2",5"
      octadienyl)-1-(2'-methylbutanoyl)benzene (2), 4,6-dihydroxy-2-O-(6"-hydroxy-3",7"
      dimethyl-2",7"-octadienyl)-1-(2'-methylbutanoyl)benzene (3), 4,6-dihydroxy-2-O
      (6"-hydroperoxy-3",7"-dimethyl-2",7"-octadienyl)-1-(2'-methylbutanoyl)benzene
      (4), and 4,6-dihydroxy-2-O-(6",7"-epoxy-3",7"-dimethyloct-2"-enyl)-1-(2'
      methylbutanoyl)benzene (5). These new natural products have been given the
      trivial names olympicins A-E (1-5). All compounds were evaluated against a panel
      of methicillin-resistant Staph. aureus and multidrug-resistant strains of Staph.
      aureus. Compound 1 exhibited minimum inhibitory concentrations (MICs) of 0.5-1
      mg/L against the tested Staph. aureus strains. Compounds 2 to 5 were also shown
      to be active, with MICs ranging from 64 to 128 mg/L. Compound 1 was synthesized
      using a simple four-step method that can be readily utilized to give a number of
      structural analogues of 1.

PMID- 21899268
TI  - (2S,3S)-sulfated pterosin C, a cytotoxic sesquiterpene from the Bangladeshi
      mangrove fern Acrostichum aureum.
AB  - Two new sesquiterpenes, (2R,3S)-sulfated pterosin C (1) and (2S,3S)-sulfated
      pterosin C (2), along with two known derivatives, (2S,3S)-pterosin C and (2R)
      pterosin P, were isolated from a methanolic extract of the aerial parts of
      Acrostichum aureum. The structures of 1 and 2 were determined by the
      interpretation of their spectroscopic data. The isolated pterosins were evaluated
      for their cytotoxic activity against the AGS, HT-29, MDA-MB-231, and MCF-7 human
      cancer cell lines and the NIH3T3 normal mouse fibroblast cell line, using the MTT
      assay. Compound 2 showed IC50 values in the range 23.9-68.8 MUM. The lowest IC50
      value (23.9 MUM) was recorded against AGS gastric adenocarcinoma cells. Compound
      2 was found to exert an apoptotic effect on AGS cells within 24 h of treatment,
      which increased with time and was greater than the positive control,
      cycloheximide. The cytotoxicity of 2 seems to be due in part to the sulfate group
      on C-14 and the configuration at C-2.

PMID- 21899269
TI  - Protective effects of luteolin against apoptotic liver damage induced by D
      galactosamine/lipopolysaccharide in mice.
AB  - In this study, the protective effects of luteolin (1, a major component of
      Cirsium japonicum) were examined against d-galactosamine
      (GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice received
      an intraperitoneal injection of 1 (25, 50, 100, and 200 mg.kg(-1)) 1 h before
      treatment with GalN (700 mg.kg(-1))/LPS (10 MUg.kg(-1)). Treatment with GalN/LPS
      resulted in increased mortality and serum aminotransferase activity. These
      increases were attenuated by pretreatment with 1. Treatment with GalN/LPS induced
      an increase in the serum level of tumor necrosis factor-alpha (TNF-alpha) and
      protein expression of TNF-alpha receptor-associated death domain, and these
      increases were prevented by 1. In addition, 1 attenuated apoptosis induced by
      GalN/LPS treatment, which was analyzed using a caspase-3 and -8 activity assay,
      as well as by proapoptotic BH3-only protein and cytochrome c protein expression,
      and by a terminal deoxynuleotidyl transferase-mediated dUTP nick end-labeling
      method. After GalN/LPS injection, nuclear phosphorylated c-Jun levels showed a
      significant increase, which were attenuated by 1. The present findings suggest
      that luteolin ameliorates D-GalN/LPS-induced liver injury and that this
      protection is likely due to inhibition of the extrinsic and intrinsic apoptotic
      pathways.

PMID- 21899270
TI  - Extraordinary enhancement of Raman scattering from pyridine on single crystal Au
      and Pt electrodes by shell-isolated Au nanoparticles.
AB  - We used shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) to
      systematically study the adsorption of pyridine on low-index Au(hkl) and Pt(hkl)
      single crystal electrodes. Our gold-core silica-shell nanoparticles (Au@SiO(2)
      NPs) boost the intensity of Raman scattering from molecules adsorbed on
      atomically flat surfaces. The average enhancement factor reaches 10(6) for
      Au(110) and 10(5) for Pt(110), which is comparable to or even greater than that
      obtained for bare gold NPs (a widely adopted SERS substrate). 3D-FDTD simulations
      reveal that this large enhancement is due to the transfer of the "hotspots" from
      NP-NP gaps to NP-surface gaps. We also found that the SHINERS intensity strongly
      depends on the surface crystallographic orientation, with differences up to a
      factor of 30. Periodic DFT calculations and theoretical analysis of dielectric
      functions indicate that this facet-dependence is predominantly governed by the
      dielectric property of the surface. The results presented in this work may open
      up new approaches for the characterization of adsorbates and reaction pathways on
      a wide range of smooth surfaces.

PMID- 21899272
TI  - Time dependent quantum dynamics study of the Ne + H2(+)(v0 = 0-4, j0 = 1) ->
      NeH(+) + H proton transfer reaction, including the Coriolis coupling. A system
      with oscillatory cross sections.
AB  - The Ne + H(2)(+)(v(0) = 0-4, j(0) = 1) proton transfer reaction has been studied
      in a wide collision energy (E(col)) interval, using the time dependent real wave
      packet method and taking into account the Coriolis coupling (CC-RWP method) and
      employing a recent ab initio potential energy surface, widely extending the
      reaction conditions previously explored at the CC level. The reaction probability
      shows a strong oscillatory behavior vs E(col) and the presence of sharp
      resonances, arising from metastable NeH(2)(+) states. The behavior of the
      reaction cross section sigma vs E(col) depends on the vibrational level and can
      in general be interpreted in terms of the late barrier character of the potential
      energy surface and the existence (or not) of threshold energy. The situation is
      particularly complex for v(0) = 2, as sigma(v0=2, j0=1) presents significant
      oscillations with E(col) up to ~0.33 eV, which probably reflect the resonances
      found in the reaction probability. Hence, it would be particularly interesting to
      investigate the Ne + H(2)(+)(v(0) = 2, j(0) = 1) reaction experimentally, as some
      resonances survive the partial wave summation. The state selected cross sections
      compare well with previous CC quantum and experimental results, and although the
      previous centrifugal sudden RWP cross sections are reasonable, the inclusion of
      the Coriolis coupling is important to achieve a quantitative description of this
      and similar systems.

PMID- 21899273
TI  - Metal complexes containing allenylidene and higher cumulenylidene ligands: a
      theoretical perspective.
AB  - Transition metal complexes containing unsaturated carbenes have enjoyed a recent
      surge in research interest. In addition to showing potential as molecular wires
      and as components of opto-electronic materials, they provide multifaceted
      reactive sites for organic synthesis. In this Account, we describe results of
      recent theoretical studies that delineate the main features of electronic
      structure and bonding in allenylidenes and higher cumulenylidene complexes,
      [L(m)M]?C(?C)(n)?CR(1)R(2) (where L represents the ligand, M the metal, and n >=
      1). Although free cumulenylidene ligands, :C(?C)(n)?CR(1)R(2), are extremely
      unstable and reactive species, they can be stabilized by coordination to a
      transition metal. The sigma-donation of the electron lone pair on the terminal
      carbon atom to an empty metal d-orbital, together with the simultaneous pi back
      donation from filled metal d(pi)-orbitals to empty cumulene pi* system orbitals,
      leads to the formation of a strong M?C bond with multiple character. Density
      functional theory studies on the model systems [(CO)(5)Cr(?C)(n)CH(2)] and [trans
      Cl(PH(3))(4)Ru(?C)(n)CH(2)](+) (where n = 1-9) have been useful in interpreting
      the structural and spectroscopic properties and the reactivity of this class of
      complexes. Geometry optimizations significantly contributed to the generalization
      of the sparse structural data available for allenylidene, butatrienylidene, and
      pentatetraenylidene complexes to higher cumulenylidene complexes (with up to
      eight carbon atoms in the chain), which show a clear structural trend. In
      particular, the geometries of all even-chain cumulenes are consistent with an
      almost purely cumulenic structure, whereas the geometries of odd-chain cumulenes
      present a significant polyyne-like carbon-carbon bond length alternation. The
      calculated bond dissociation energies (BDEs) of the cumulenylidene ligand remain
      almost constant on lengthening the cumulene chain. These BDEs indicate that there
      is no thermodynamic upper limit to the cumulene chain length and suggest that the
      synthetic difficulties in preparing higher cumulenylidenes are due to an increase
      in reactivity. The calculated charges on the carbon atoms show no significant
      polarization along the cumulene chain, indicating that charge distribution is not
      important in determining the regioselectivity of either electrophilic or
      nucleophilic attack, which is instead determined by frontier orbital factors. The
      breakdown of the contributions from the metal and the carbon atoms along the
      chain to the HOMO and LUMO shows that the HOMO has contributions mainly from the
      metal and the carbon atoms in even positions along the chain (C(2), C(4), C(6),
      and higher). In contrast, the LUMO has contributions mainly from the carbon atoms
      in odd positions along the chain (C(1), C(3), C(5), and higher), thus explaining
      the experimentally observed regioselectivity of electrophilic and nucleophilic
      attacks, which are directed, respectively, to even and odd positions of the
      cumulenylidene chain. The study of the electronic structure of cumulenylidenes
      has allowed us not only to give a consistent rationale for the main structural
      and spectroscopic properties and for the reactivity of this emerging class of
      compounds but also to predict the effect of ancillary ligands on the metal center
      or substituents on the carbon end. The result is a useful guide to new
      developments in the still-underexplored fields of this fascinating class of
      compounds.

PMID- 21899274
TI  - Structure, dynamics, and reactivity of hydrated electrons by ab initio molecular
      dynamics.
AB  - Understanding the properties of hydrated electrons, which were first observed
      using pulse radiolysis of water in 1962, is crucial because they are key species
      in many radiation chemistry processes. Although time-resolved spectroscopic
      studies and molecular simulations have shown that an electron in water (prepared,
      for example, by water photoionization) relaxes quickly to a localized, cavity
      like structure ~2.5 A in radius, this picture has recently been questioned. In
      another experimental approach, negatively charged water clusters of increasing
      size were studied with photoelectron and IR spectroscopies. Although small water
      clusters can bind an excess electron, their character is very different from bulk
      hydrated species. As data on electron binding in liquid water have become
      directly accessible experimentally, the cluster-to-bulk extrapolations have
      become a topic of lively debate. Quantum electronic structure calculations
      addressing experimental measurables have, until recently, been largely limited to
      small clusters; extended systems were approached mainly with pseudopotential
      calculations combining a classical description of water with a quantum mechanical
      treatment of the excess electron.  In this Account, we discuss our investigations
      of electrons solvated in water by means of ab initio molecular dynamics
      simulations. This approach, applied to a model system of a negatively charged
      cluster of 32 water molecules, allows us to characterize structural, dynamical,
      and reactive aspects of the hydrated electron using all of the system's valence
      electrons. We show that under ambient conditions, the electron localizes into a
      cavity close to the surface of the liquid cluster. This cavity is, however, more
      flexible and accessible to water molecules than an analogous area around
      negatively charged ions.  The dynamical process of electron attachment to a
      neutral water cluster is strongly temperature dependent. Under ambient
      conditions, the electron relaxes in the liquid cluster and becomes
      indistinguishable from an equilibrated, solvated electron on a picosecond time
      scale. In contrast, for solid, cryogenic systems, the electron only partially
      localizes outside of the cluster, being trapped in a metastable, weakly bound
      "cushion-like" state. Strongly bound states under cryogenic conditions could only
      be prepared by cooling equilibrated, liquid, negatively charged clusters. These
      calculations allow us to rationalize how different isomers of electrons in
      cryogenic clusters can be observed experimentally. Our results also bring into
      question the direct extrapolation of properties of cryogenic, negatively charged
      water clusters to those of electrons in the bulk liquid.  Ab initio molecular
      dynamics represents a unique computational tool for investigating the reactivity
      of the solvated electron in water. As a prototype, the electron-proton reaction
      was followed in the 32-water cluster. In accord with experiment, the molecular
      mechanism is a proton transfer process that is not diffusion limited, but rather
      controlled by a proton-induced deformation of the excess electron's solvent
      shell. We demonstrate the necessary ingredients of a successful density
      functional methodology for the hydrated electron that avoids potential pitfalls,
      such as self-interaction error, insufficient basis set, or lack of dispersion
      interactions. We also benchmark the density functional theory methods and outline
      the path to faithful ab initio simulations of dynamics and reactivity of
      electrons solvated in extended aqueous systems.

PMID- 21899275
TI  - Pretreatment with an ethanolic extract of Taiwanofungus camphoratus (Antrodia
      camphorata) enhances the cytotoxic effects of amphotericin B.
AB  - Taiwanofungus camphoratus, a well-known Chinese medicine used in Taiwan,
      possesses several pharmacological functions, including anticancer effects. In the
      present study, we aimed to investigate a novel anticancer effect by pretreating
      cancer cells with an ethanolic extract of T. camphoratus (TCEE) followed by the
      administration of an antifungal agent amphotericin B (AmB). Both TCEE and AmB
      showed significant dose-dependent cytotoxicity in HT29 cells. Pretreatment with a
      nontoxic dose of TCEE enhanced the cytotoxicity of AmB. Furthermore, significant
      apoptotic cell death was found in cells treated with TCEE and AmB. A combination
      treatment with AmB plus TCEE resulted in a significant repression of tumor growth
      in HT29 xenografts. Collectively, our results indicated that combined treatment
      with AmB and TCEE effectively induced apoptosis and inhibited tumor growth. In
      the future, TCEE may serve as a potential complementary and alternative medicine
      to treat patients suffering from colorectal cancer.

PMID- 21899276
TI  - Formation of gallaoxetanes: C-O activation of 1,2-epoxybutane by ground-state Ga
      atoms.
AB  - (69/71)Ga atoms were reacted with 1,2-epoxybutane and its isotopomers, 1,2
      epoxybutane-1,1-d(2) (CH(3)CH(2)CHOCD(2)) and 1,2-epoxybutane-2-d(1)
      (CH(3)CH(2)CDOCH(2)), under matrix-isolation conditions. The novel gallaoxetanes
      CH(3)CH(2)CHCH(2)GaO and CH(3)CH(2)CHCH(2)OGa, resulting from the insertion of
      the metal atom in the C(1)-O and C(2)-O bonds, respectively, of the 1,2
      epoxybutane, were detected by EPR spectroscopy. The Ga and H hyperfine
      interaction (hfi) values of the gallaoxetanes, calculated using a DFT method,
      were used to help assign the EPR spectra. A third Ga-centered species, detected
      at 190 K, underwent spectral changes similar to those of the C(2)-O insertion
      product upon isotopic substitution of the 1,2-epoxybutane. Although the Ga hfi
      for this species was 36% smaller than that of the C(2)-O insertion product, the
      values for the H hfi were similar, suggesting that the carrier of the spectrum
      was the C(2)-O insertion product where Ga was perturbed by the matrix
      constraints. The alkyl radical CH(3)CH(2)(*CH)CH(2)OGa, resulting from ring
      opening at the C(2)-O bond of 1,2-epoxybutane, was observed at temperatures below
      150 K. This radical has been implicated in the formation of the C(2)-O insertion
      product. The unusually small value found for two of the beta-hydrogens of the
      alkyl radical is discussed.

PMID- 21899277
TI  - Amino acid determinants of substrate selectivity in the Trypanosoma brucei
      sphingolipid synthase family.
AB  - The substrate selectivity of four Trypanosoma brucei sphingolipid synthases was
      examined. TbSLS1, an inositol phosphorylceramide (IPC) synthase, and TbSLS4, a
      bifunctional sphingomyelin (SM)/ethanolamine phosphorylceramide (EPC) synthase,
      were inactivated by Ala substitutions of a conserved triad of residues His210,
      His253, and Asp257 thought to form part of the active site. TbSLS4 also catalyzed
      the reverse reaction, production of ceramide from sphingomyelin, but none of the
      Ala substitutions of the catalytic triad in TbSLS4 were able to do so. Site
      directed mutagenesis identified residues proximal to the conserved triad that
      were responsible for the discrimination between charge and size of the different
      head groups. For discrimination between anionic (phosphoinositol) and
      zwitterionic (phosphocholine, phosphoethanolamine) head groups, doubly mutated
      V172D/S252F TbSLS1 and D172V/F252S TbSLS3 showed reciprocal conversion between
      IPC and bifunctional SM/EPC synthases. For differentiation of zwitterionic
      headgroup size, N170A TbSLS1 and A170N/N187D TbSLS4 showed reciprocal conversion
      between EPC and bifunctional SM/EPC synthases. These studies provide a mapping of
      the SLS active site and demonstrate that differences in catalytic specificity of
      the T. brucei enzyme family are controlled by natural variations in as few as
      three residue positions.

PMID- 21899278
TI  - Solution-processed flexible polymer solar cells with silver nanowire electrodes.
AB  - The conventional anode for organic photovoltaics (OPVs), indium tin oxide (ITO),
      is expensive and brittle, and thus is not suitable for use in roll-to-roll
      manufacturing of OPVs. In this study, fully solution-processed polymer bulk
      heterojunction (BHJ) solar cells with anodes made from silver nanowires (Ag NWs)
      have been successfully fabricated with a configuration of Ag NWs/poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/polymer:phenyl-C(61)
      butyric acid methyl ester (PCBM)/Ca/Al. Efficiencies of 2.8 and 2.5% are obtained
      for devices with Ag NW network on glass and on poly(ethylene terephthalate)
      (PET), respectively. The efficiency of the devices is limited by the low work
      function of the Ag NWs/PEDOT:PSS film and the non-ideal ohmic contact between the
      Ag NW anode and the active layer. Compared with devices based on the ITO anode,
      the open-circuit voltage (V(oc)) of solar cells based on the Ag NW anode is lower
      by ~0.3 V. More importantly, highly flexible BHJ solar cells have been firstly
      fabricated on Ag NWs/PET anode with recoverable efficiency of 2.5% under large
      deformation up to 120 degrees . This study indicates that, with improved
      engineering of the nanowires/polymer interface, Ag NW electrodes can serve as a
      low-cost, flexible alternative to ITO, and thereby improve the economic viability
      and mechanical stability of OPVs.

PMID- 21899279
TI  - Neon Ion Beam Lithography (NIBL).
AB  - Existing techniques for electron- and ion-beam lithography, routinely employed
      for nanoscale device fabrication and mask/mold prototyping, do not simultaneously
      achieve efficient (low fluence) exposure and high resolution. We report
      lithography using neon ions with fluence <1 ion/nm(2), ~1000* more efficient than
      using 30 keV electrons, and resolution down to 7 nm half-pitch. This combination
      of resolution and exposure efficiency is expected to impact a wide array of
      fields that are dependent on beam-based lithography.

PMID- 21899280
TI  - Supramolecular engineering of intrinsic and extrinsic porosity in covalent
      organic cages.
AB  - Control over pore size, shape, and connectivity in synthetic porous materials is
      important in applications such as separation, storage, and catalysis. Crystalline
      organic cage molecules can exhibit permanent porosity, but there are few
      synthetic methods to control the crystal packing and hence the pore connectivity.
      Typically, porosity is either 'intrinsic' (within the molecules) or 'extrinsic'
      (between the molecules)--but not both. We report a supramolecular approach to the
      assembly of porous organic cages which involves bulky directing groups that
      frustrate the crystal packing. This generates, in a synthetically designed
      fashion, additional 'extrinsic' porosity between the intrinsically porous cage
      units. One of the molecular crystals exhibits an apparent Brunauer-Emmett-Teller
      surface area of 854 m(2) g(-1), which is higher than that of unfunctionalized
      cages of the same dimensions. Moreover, connectivity between pores, and hence
      guest uptakes, can be modulated by the introduction of halogen bonding motifs in
      the cage modules. This suggests a broader approach to the supramolecular
      engineering of porosity in molecular organic crystals.

PMID- 21899281
TI  - A tumor-environment-responsive nanocarrier that evolves its surface properties
      upon sensing matrix metalloproteinase-2 and initiates agglomeration to enhance T2
      relaxivity for magnetic resonance imaging.
AB  - We designed and synthesized a modified ferritin as a tumor-environment-responsive
      nanocarrier. We found that this nanocarrier could evolve its surface properties
      upon sensing a tumor-associated protease, matrix metalloproteinase-2 (MMP-2),
      which initiated agglomeration, resulting in the enhancement of T(2) relaxivity
      for magnetic resonance imaging (MRI). The designed ferritin contained a triad of
      modifiers composed of (i) a "sensing" segment (substrate peptide of MMP-2), (ii)
      "hydrophobic" segments and (iii) a "hydrophilic" segment of polyethylene glycol
      (PEG). The hydrophilic segment ensured the particles' monodispersibility in
      aqueous conditions. In the presence of MMP-2 activity, the "sensing" segment was
      cleaved by the enzyme and its submerged "hydrophobic" segments were exposed on
      the surface, resulting in the initiation of aggregation. Because ferritin
      contains ferrihydrite in its inner space, this multimerization resulted in the
      enhancement of T(2) relaxivity, suggesting that this nanocarrier may be useful as
      a contrast agent in MRI.

PMID- 21899283
TI  - Expedient Route to the functionalized calyciphylline A-type skeleton via a
      Michael addition-RCM strategy.
AB  - An efficient, robust, and scalable strategy to access the functionalized core of
      calyciphylline A-type alkaloids has been developed starting from commercially
      available 3-methylanisole. Key features of this approach are an intramolecular
      Michael addition/allylation sequence and a ring-closing metathesis step.

PMID- 21899284
TI  - A modular reaction pairing approach to the diversity-oriented synthesis of fused-
      and bridged-polycyclic sultams.
AB  - A reaction pairing strategy centered on utilization of a reaction triad
      (sulfonylation, S(N)Ar addition and Mitsunobu alkylation) generating skeletally
      diverse, tricyclic and bicyclic benzofused sultams is reported. Pairing
      sulfonylation and S(N)Ar reactions yields bridged, tricyclic and bicyclic
      benzofused sultams. Application of the Mitsunobu reaction in a sulfonylation
      Mitsunobu-S(N)Ar pairing allows access to benzthiazocine-1,1-dioxides, while a
      simple change in the order of pairing to sulfonylation-S(N)Ar-Mitsunobu affords
      structurally different, bridged tricyclic benzofused sultams.

PMID- 21899285
TI  - Predictive model for ice formation on superhydrophobic surfaces.
AB  - The prevention and control of ice accumulation has important applications in
      aviation, building construction, and energy conversion devices. One area of
      active research concerns the use of superhydrophobic surfaces for preventing ice
      formation. The present work develops a physics-based modeling framework to
      predict ice formation on cooled superhydrophobic surfaces resulting from the
      impact of supercooled water droplets. This modeling approach analyzes the
      multiple phenomena influencing ice formation on superhydrophobic surfaces through
      the development of submodels describing droplet impact dynamics, heat transfer,
      and heterogeneous ice nucleation. These models are then integrated together to
      achieve a comprehensive understanding of ice formation upon impact of liquid
      droplets at freezing conditions. The accuracy of this model is validated by its
      successful prediction of the experimental findings that demonstrate that
      superhydrophobic surfaces can fully prevent the freezing of impacting water
      droplets down to surface temperatures of as low as -20 to -25  degrees C. The
      model can be used to study the influence of surface morphology, surface
      chemistry, and fluid and thermal properties on dynamic ice formation and identify
      parameters critical to achieving icephobic surfaces. The framework of the present
      work is the first detailed modeling tool developed for the design and analysis of
      surfaces for various ice prevention/reduction strategies.

PMID- 21899286
TI  - Peroxynitrous-acid-induced chemiluminescence of fluorescent carbon dots for
      nitrite sensing.
AB  - In this work, chemiluminescent (CL) property of the carbon dots in the presence
      of peroxynitrous acid was studied. Peroxynitrous acid is formed by online mixing
      of nitrite and acidified hydrogen peroxide. The CL intensity was increased
      linearly with nitrite concentration in the range from 1.0 * 10(-7) M to 1.0 * 10(
      5) M, and the detection limit was 5.3 * 10(-8) M (signal-to-noise ratio of S/N =
      3). This method has been successfully applied to the determination of nitrites in
      pond water, river water, and pure milk, with recoveries in the range of 98%-108%.
      The CL mechanism of the peroxynitrous acid-carbon dots system was investigated
      using the CL, ultraviolet-visible light (UV-vis), and electron paramagnetic
      resonance (EPR) spectra. The electron-transfer annihilation of hole-injected and
      electron-injected carbon dots could mainly account for the CL emission, which
      sheds new light on the optical properties of the carbon dots.

PMID- 21899287
TI  - Second harmonic generation and hyperpolarizabilities of the double-cubane
      compound [Sb7S8Br2](AlCl4)3: chalcogenide in ionic liquids.
AB  - Because noncentrosymmetric [Sb7S8Br2](AlCl4)3 single crystals possess a wide
      optical transparency region, it is a promising material for nonlinear optical
      applications. We have calculated the dispersion of linear and nonlinear optical
      susceptibilities including optical second harmonic generation (SHG) using a
      relaxed geometry. We find that the fundamental optical absorption edge situated
      at about 2.03 eV is in excellent agreement with the experimental data.
      Calculations of epsilon(2)(xx)(omega), epsilon(2)(yy)(omega), and
      epsilon(2)(zz)(omega) tensor components of the frequency-dependent dielectric
      function are presented. The single crystal possesses a considerable anisotropy of
      linear optical susceptibilities, which usually favors an enhanced phase matching
      conditions necessary to observe SHG and optical parametric oscillator (OPO)
      effects. Our calculations show that, in [Sb7S8Br2](AlCl4)3, |chi123(2)(omega)| is
      the principal tensor component having the highest value of SHG at zero frequency
      limit as well as at 1.165 eV (lambda = 1064 nm) laser wavelength generation. The
      microscopic second-order hyperpolarizability, beta123, of the dominant SHG
      component is calculated at the static limit and at lambda = 1064 nm.

PMID- 21899288
TI  - Real-time monitoring of surface-initiated atom transfer radical polymerization
      using silicon photonic microring resonators: implications for combinatorial
      screening of polymer brush growth conditions.
AB  - We directly monitor in parallel and in real time the temporal profiles of polymer
      brushes simultaneously grown via multiple ATRP reaction conditions on a single
      substrate using arrays of silicon photonic microring resonators. In addition to
      probing relative polymerization rates, we show the ability to evaluate the
      dynamic properties of the in situ grown polymers. This presents a powerful new
      platform for studying modified interfaces that may allow for the combinatorial
      optimization of surface-initiated polymerization conditions.

PMID- 21899289
TI  - Tissue-specific expression of p53 and ras genes in response to the environmental
      genotoxicant benzo(alpha)pyrene in marine mussels.
AB  - Marine mussels can develop hemeic and gonadal neoplasia in the natural
      environment. Associated with these diseases are the tumor suppressor (TS) p53 and
      the proto-oncogene ras coded proteins, both of which are highly conserved among
      molluscs and vertebrates. We report, for the first time, tissue-specific
      expression analysis of p53 and ras genes in Mytilus edulis by means of
      quantitative RT-PCR. A tissue-specific response was observed after 6 and 12 days
      exposure to a sublethal concentration of a model Polycyclic Aromatic Hydrocarbon
      (PAH), benzo(alpha)pyrene (B(alpha)P). This sublethal concentration (56 MUg/L)
      was selected based on an integrated biomarker analysis carried out prior to gene
      expression analysis, which included a 'clearance rate' assay, histopathological
      analysis, and DNA strand break measurements. The results indicated that the
      selected concentration of B(alpha)P can lead to the induction of DNA strand
      breaks, tissue damage, and expression of tumor-regulating genes. Both p53 and ras
      are expressed in a tissue-specific manner, which collaborate with tissue-specific
      function in response to genotoxic stress. The integrated biological responses in
      Mytilus edulis strengthen the use of this organism to investigate the fundamental
      mechanism of development of malignancy in invertebrate which could be translated
      to other organisms including humans.

PMID- 21899290
TI  - Evolution and protein packaging of small-molecule RNA aptamers.
AB  - A high-affinity RNA aptamer (K(d) = 50 nM) was efficiently identified by SELEX
      against a heteroaryldihydropyrimidine structure, chosen as a representative drug
      like molecule with no cross reactivity with mammalian or bacterial cells. This
      aptamer, its weaker-binding variants, and a known aptamer against theophylline
      were each embedded in a longer RNA sequence that was encapsidated inside a virus
      like particle by a convenient expression technique. These nucleoprotein particles
      were shown by backscattering interferometry to bind to the small-molecule ligands
      with affinities similar to those of the free (nonencapsidated) aptamers. The
      system therefore comprises a general approach to the production and sequestration
      of functional RNA molecules, characterized by a convenient label-free analytical
      technique.

PMID- 21899291
TI  - Gene quantification by the NanoGene assay is resistant to inhibition by humic
      acids.
AB  - NanoGene assay is a magnetic bead and quantum dot nanoparticles based gene
      quantification assay. It relies on a set of probe and signaling probe DNAs to
      capture the target DNA via hybridization. We have demonstrated the inhibition
      resistance of the NanoGene assay using humic acids laden genomic DNA (gDNA). At 1
      MUg of humic acid per mL, quantitiative PCR (qPCR) was inhibited to 0% of its
      quantification capability whereas NanoGene assay was able to maintain more than
      60% of its quantification capability. To further increase the inhibition
      resistance of NanoGene assay at high concentration of humic acids, we have
      identified the specific mechanisms that are responsible for the inhibition. We
      examined five potential mechanisms with which the humic acids can partially
      inhibit our NanoGene assay. The mechanisms examined were (1) adsorption of humic
      acids on the particle surface; (2) particle aggregation induced by humic acids;
      (3) fluorescence quenching of quantum dots by humic acids during hybridization;
      (4) humic acids mimicking of target DNA; and (5) nonspecific binding between
      humic acids and target gDNA. The investigation showed that no adsorption of humic
      acids onto the particles' surface was observed for the humic acids'
      concentration. Particle aggregation and fluorescence quenching were also
      negligible. Humic acids also did not mimic the target gDNA except 1000 MUg of
      humic acids per mL and hence should not contribute to the partial inhibition.
      Four of the above mechanisms were not related to the inhibition effect of humic
      acids particularly at the environmentally relevant concentrations (<100 MUg/mL).
      However, a substantial amount of nonspecific binding was observed between the
      humic acids and target gDNA. This possibly results in lesser amount of target
      gDNA being captured by the probe and signaling DNA.

PMID- 21899292
TI  - Discovery of (+)-N-(3-aminopropyl)-N-[1-(5-benzyl-3-methyl-4-oxo
      [1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4-methylbenzamide (AZD4877),
      a kinesin spindle protein inhibitor and potential anticancer agent.
AB  - Structure-activity relationship analysis identified (+)-N-(3-aminopropyl)-N-[1-(5
      benzyl-3-methyl-4-oxo-[1,2]thiazolo[5,4-d]pyrimidin-6-yl)-2-methylpropyl]-4
      methylbenzamide (AZD4877), from a series of novel kinesin spindle protein (KSP)
      inhibitors, as exhibiting both excellent biochemical potency and pharmaceutical
      properties suitable for clinical development. The selected compound arrested
      cells in mitosis leading to the formation of the monopolar spindle phenotype
      characteristic of KSP inhibition and induction of cellular death. A favorable
      pharmacokinetic profile and notable in vivo efficacy supported the selection of
      this compound as a clinical candidate for the treatment of cancer.

PMID- 21899293
TI  - New functionalized flexible Al-MIL-53-X (X = -Cl, -Br, -CH3, -NO2, -(OH)2)
      solids: syntheses, characterization, sorption, and breathing behavior.
AB  - Five new flexible functionalized aluminum hydroxo terephthalates [Al(OH)(BDC
      X)].n(guests) (BDC = 1,4-benzene-dicarboxylate; X = -Cl, 1-Cl; -Br, 2-Br; -CH(3),
      3-CH(3); -NO(2), 4-NO(2); -(OH)(2), 5-OH(2)) were synthesized under solvothermal
      conditions. The as synthesized (Al-MIL-53-X-AS) as well as the activated
      compounds were characterized by X-ray powder diffraction (XRPD), IR spectroscopy,
      thermogravimetric (TG), and elemental analysis. Activation, that is, removal of
      unreacted H(2)BDC-X molecules and/or occluded solvent molecules, followed by
      hydration in air at room temperature, led to the narrow pore (NP) form of the
      title compounds [Al(OH)(BDC-X)].n(H(2)O) (Al-MIL-53-X). Thermogravimetric
      analysis (TGA) and temperature-dependent XRPD (TDXRPD) experiments performed on
      the NP-form of the compounds indicate high thermal stability in the range 325-500
      degrees C. As verified by N(2), CO(2), or H(2)O sorption measurements, most of
      the thermally activated compounds exhibit significant microporosity. Similar to
      pristine Al-MIL-53, the present compounds retain their structural flexibility
      depending on the nature of guest molecules and temperature, as verified by cell
      parameter determination from XRPD data. The breathing behavior of the
      functionalized frameworks upon dehydration-rehydration, investigated by
      temperature and time-dependent XRPD measurements, differs significantly compared
      to parent Al-MIL-53.

PMID- 21899294
TI  - Synthesis and reactivity of new Ni, Pd, and Pt 2,6-bis(di-tert
      butylphosphinito)pyridine pincer complexes.
AB  - Synthesis and characterization of new (PONOP) [2,6-bis(di-tert
      butylphosphinito)pyridine] metal (Ni, Pd, Pt) complexes are reported.
      Surprisingly, these compounds [(PONOP)MCl]Cl in the presence of 1 equiv of
      superhydride (LiEt(3)BH) formed a new class of complexes (H-PONOP)MCl, in which
      the pyridine ring in the PONOP ligand lost its aromaticity as a result of hydride
      attack at the para position of the ring. The new Ni-H compound [(H-PONOP)NiH] was
      synthesized by reacting (H-PONOP)NiCl with 1 equiv of superhydride. Analogous Pd
      and Pt compounds were prepared. Reactivity of these new pincer complexes toward
      MeLi and PhLi also has been studied. These Ni complexes catalyzed the
      hydrosilylation of aldehyde. In some cases characterization of new (PONOP)M
      complexes was difficult because of high instability due to degradation of the P-O
      bond.

PMID- 21899295
TI  - Switching the reactivity of dihydrothiopyran-4-one with aldehydes by aqueous
      organocatalysis: Baylis-Hillman, aldol, or aldol condensation reactions.
AB  - An aqueous medium containing catalytic amounts of a tertiary amine was employed
      to direct the chemoselectivity of the reaction of aldehydes with 1a. With DBU, 2
      was formed at room temperature as a rare exemplary of Baylis-Hillman reactions in
      heterocyclic enones. DABCO alternated the pathway toward an aldol reaction to
      form syn/anti mixtures of 3 with the syn isomers being the major products. With
      Et(3)N, aldol condensation dominated.

PMID- 21899296
TI  - Immunosuppressive effects of fisetin in ovalbumin-induced asthma through
      inhibition of NF-kappaB activity.
AB  - Fisetin, a flavonoid compound commonly present in fruits and vegetables, can
      exert anti-inflammation activities via inhibition of the NF-kappaB-signaling
      pathway. This study aims to evaluate the antiasthma activity of fisetin and
      investigate its possible molecular mechanisms. We found that fisetin attenuated
      lung inflammation, goblet cell hyperplasia, and airway hyperresponsiveness in
      ovalbumin-induced asthma and decreased eosinophils and lymphocytes in
      bronchoalveolar lavage fluid. Fisetin treatment reduced expression of the key
      initiators of allergic airway inflammation (eotaxin-1 and TSLP), Th2-associated
      cytokines (IL-4, IL-5, and IL-13) in lungs, and Th2-predominant transcription
      factor GATA-3 and cytokines in thoracic lymph node cells and splenocytes.
      Notably, fisetin treatment impaired NF-kappaB activation in OVA-stimulated lung
      tissues and TNF-alpha-stimulated bronchial epithelial cells. Collectively, this
      study demonstrated the beneficial effect of fisetin in the amelioration of
      asthmatic phenotypes. The antiasthma activity of fisetin is associated with
      reduction of Th2 responses as well as suppression of NF-kappaB and its downstream
      chemokines.

PMID- 21899297
TI  - The molecular interactions that stabilize RNA tertiary structure: RNA motifs,
      patterns, and networks.
AB  - RNA molecules adopt specific three-dimensional structures critical to their
      function. Many essential metabolic processes, including protein synthesis and RNA
      splicing, are carried out by RNA molecules with elaborate tertiary structures
      (e.g.  3QIQ, right). Indeed, the ribosome and self-splicing introns are complex
      RNA machines. But even the coding regions in messenger RNAs and viral RNAs are
      flanked by highly structured untranslated regions, which provide regulatory
      information necessary for gene expression.  RNA tertiary structure is defined as
      the three-dimensional arrangement of RNA building blocks, which include helical
      duplexes, triple-stranded structures, and other components that are held together
      through connections collectively termed RNA tertiary interactions. The structural
      diversity of these interactions is now a subject of intense investigation,
      involving the techniques of NMR, X-ray crystallography, chemical genetics, and
      phylogenetic analysis. At the same time, many investigators are using biophysical
      techniques to elucidate the driving forces for tertiary structure formation and
      the mechanisms for its stabilization. RNA tertiary folding is promoted by
      maximization of base stacking, much like the hydrophobic effect that drives
      protein folding. RNA folding also requires electrostatic stabilization, both
      through charge screening and site binding of metals, and it is enhanced by
      desolvation of the phosphate backbone. In this Account, we provide an overview of
      the features that specify and stabilize RNA tertiary structure.  A major
      determinant for overall tertiary RNA architecture is local conformation in
      secondary-structure junctions, which are regions from which two or more duplexes
      project. At junctions and other structures, such as pseudoknots and kissing
      loops, adjacent helices stack on one another, and these coaxial stacks play a
      major role in dictating the overall architectural form of an RNA molecule. In
      addition to RNA junction topology, a second determinant for RNA tertiary
      structure is the formation of sequence-specific interactions. Networks of triple
      helices, tetraloop-receptor interactions, and other sequence-specific contacts
      establish the framework for the overall tertiary fold. The third determinant of
      tertiary structure is the formation of stabilizing stacking and backbone
      interactions, and many are not sequence specific. For example, ribose zippers
      allow 2'-hydroxyl groups on different RNA strands to form networks of
      interdigitated hydrogen bonds, serving to seal strands together and thereby
      stabilize adjacent substructures. These motifs often require monovalent and
      divalent cations, which can interact diffusely or through chelation to specific
      RNA functional groups.  As we learn more about the components of RNA tertiary
      structure, we will be able to predict the structures of RNA molecules from their
      sequences, thereby obtaining key information about biological function.
      Understanding and predicting RNA structure is particularly important given the
      recent discovery that although most of our genome is transcribed into RNA
      molecules, few of them have a known function. The prevalence of RNA viruses and
      pathogens with RNA genomes makes RNA drug discovery an active area of research.
      Finally, knowledge of RNA structure will facilitate the engineering of
      supramolecular RNA structures, which can be used as nanomechanical components for
      new materials. But all of this promise depends on a better understanding of the
      RNA parts list, and how the pieces fit together.

PMID- 21899298
TI  - Suzuki-Miyaura cross-coupling of heteroaryl halides and arylboronic acids in
      continuous flow.
AB  - General continuous-flow conditions for the Suzuki-Miyaura cross-coupling of
      heteroaryl halides and (hetero)arylboronic acids have been developed. A wide
      range of heterobiaryl products is obtained in excellent yields (20 examples)
      employing low catalyst loadings (0.05-1.5 mol % Pd).

PMID- 21899299
TI  - A quantitative immunopolymerase chain reaction method for detection of vegetative
      insecticidal protein in genetically modified crops.
AB  - Vegetative insecticidal protein (Vip) is being employed for transgenic expression
      in selected crops such as cotton, brinjal, and corn. For regulatory compliance,
      there is a need for a sensitive and reliable detection method, which can
      distinguish between approved and nonapproved genetically modified (GM) events and
      quantify GM contents as well. A quantitative immunopolymerase chain reaction
      (IPCR) method has been developed for the detection and quantification of Vip
      protein in GM crops. The developed assay displayed a detection limit of 1 ng/mL
      (1 ppb) and linear quantification range between 10 and 1000 ng/mL of Vip-S
      protein. The sensitivity of the assay was found to be 10 times higher than an
      analogous enzyme-linked immunosorbent assay for Vip-S protein. The results
      suggest that IPCR has the potential to become a standard method to quantify GM
      proteins.

PMID- 21899300
TI  - Heterogeneous liposome membranes with pH-triggered permeability enhance the in
      vitro antitumor activity of folate-receptor targeted liposomal doxorubicin.
AB  - The killing efficacy of doxorubicin from liposome-based delivery carriers has
      been shown to correlate strongly with its intracellular trafficking and, in
      particular, its fast and extensive release from the delivery carrier. However,
      previously explored pH-triggered mechanisms that were designed to become
      activated during liposome endocytosis have also been shown to interfere with the
      liposome stability in vivo. We have designed pH-triggered gel-phase liposomes
      with heterogeneous membranes for the delivery of doxorubicin. These liposomes are
      triggered to form "leaky" interfacial boundaries between gel-gel phase separated
      domains on the membrane bilayer with lowering pH. The pH-triggered mechanism does
      not compromise liposome stability in vivo and results in superior in vitro
      killing efficacy of delivered doxorubicin when liposomes are endocytosed by a
      clathrin-mediated pathway. In the present work, we evaluate the general
      applicability of these liposomes when targeted to the folate receptor (FR) of KB
      cancer cells in vitro and become endocytosed by a less acidic pathway: the
      caveolae pathway. FR-targeting liposomes exhibit almost 50% decrease in cell
      association for increase in liposome size from 120 to 280 nm in diameter after
      relatively short incubation times (up to 4 h). The fraction of internalized
      vesicles, however, is approximately 60% of the cell associated vesicles
      independent of their size. Our findings demonstrate that, for the same
      doxorubicin uptake per cancer cell, the killing effect of doxorubicin delivered
      by pH-triggered lipid vesicles is greater (IC(50) = 0.032 mM for a 6 h
      incubation) than when delivered by a conventional non-pH-responsive composition
      (IC(50) = 0.194 mM). These findings suggest higher bioexposure of cells to the
      therapeutic agent possibly via faster and more extensive release from the
      carrier. Animal studies of FR-targeting non-pH-responsive liposomal doxorubicin
      report stronger therapeutic potential for the targeted approach relative to
      nontargeted liposomes and to free doxorubicin. The findings of the present study
      suggest that the targeted pH-triggered liposomes could potentially further
      enhance the therapeutic outcomes of doxorubicin in vivo.

PMID- 21899301
TI  - Highly efficient FRET from a single nitrogen-vacancy center in nanodiamonds to a
      single organic molecule.
AB  - We show highly efficient fluorescence resonance energy transfer (FRET) between
      negatively charged nitrogen-vacancy (NV) centers in diamond as donor and dye
      molecules as acceptor, respectively. The energy transfer efficiency is 86% with
      particles of 20 nm in size. Calculated and experimentally measured energy
      transfer efficiencies are in excellent agreement. Owing to the small size of the
      nanocrystals and careful surface preparation, energy transfer between a single
      nitrogen-vacancy center and a single quencher was identified by the stepwise
      change of energy transfer efficiencies due to bleaching of single acceptor
      molecules. Our studies pave the way toward FRET-based scanning probe techniques
      using single NV donors.

PMID- 21899302
TI  - The effects of protein environment and dispersion on the formation of ferric
      superoxide species in myo-inositol oxygenase (MIOX): a combined ONIOM(DFT:MM) and
      energy decomposition analysis.
AB  - The catalytic reaction of myo-inositol oxygenase, a nonheme diiron enzyme, is
      initiated by the binding of an O(2) molecule to the ferrous center of a mixed
      valence Fe(II)Fe(III) intermediate. This generates a (superoxo)Fe(III)Fe(III)
      reactive species that abstracts a hydrogen atom from the myo-inositol substrate.
      To understand the effects of protein environment and intracluster dispersion on
      this O(2)-binding process, we undertook a combined ONIOM(B3LYP:AMBER) and energy
      decomposition analysis. The interaction energy between the active site and the
      thousands of atoms present in the protein environment was decomposed into
      electrostatic, van der Waals (vdW) and polarization terms. These terms were
      further decomposed into contributions from individual amino acid residues. The
      dispersion effect, which is not adequately accounted for by the B3LYP method, was
      estimated in an empirical manner. The results show that the electrostatic, vdW,
      and polarization effects slightly enhance the O(2) binding process. The
      dispersion effect enhances O(2) binding more significantly than these effects.
      Despite these stabilizing effects, the entropy effect disfavors O(2) binding,
      making the process almost thermoneutral.

PMID- 21899303
TI  - Horizontal transfer of PAH catabolism genes in Mycobacterium: evidence from
      comparative genomics and isolated pyrene-degrading bacteria.
AB  - Biodegradation of high molecular weight polycyclic aromatic hydrocarbons (PAHs),
      such as pyrene and benzo[a]pyrene, has only been observed in a few genera, namely
      fast-growing Mycobacterium and Rhodococcus. In M. vanbaalenii PYR-1, multiple
      aromatic ring hydroxylating dioxygenase (ARHDOs) genes including pyrene
      dioxygenases nidAB and nidA3B3 are localized in one genomic region. Here we
      examine the homologous genomic regions in four other PAH-degrading Mycobacterium
      (strains JLS, KMS, and MCS, and M. gilvum PYR-GCK), presenting evidence for past
      horizontal gene transfer events. Seven distinct types of ARHDO genes are present
      in all five genomes, and display conserved syntenic architecture with respect to
      gene order, orientation, and association with other genes. Duplications and
      putative integrase and transposase genes suggest past gene shuffling. To
      corroborate these observations, pyrene-degrading strains were isolated from two
      PAH-contaminated sediments: Chattanooga Creek (Tennessee) and Lake Erie (western
      basin). Some were related to fast-growing Mycobacterium spp. and carried both
      nidA and nidA3 genes. Other isolates belonged to Microbacteriaceae and
      Intrasporangiaceae presenting the first evidence of pyrene degradation in these
      families. These isolates had nidA (and some, nidA3) genes that were homologous to
      Mycobacterial ARHDO genes, suggesting that horizontal gene transfer events have
      occurred.

PMID- 21899305
TI  - Pyrophosphate-selective fluorescent chemosensor based on 1,8-naphthalimide-DPA
      Zn(II) complex and its application for cell imaging.
AB  - A new zinc(II) complex with a two-dipicolylamine-substituted 1,8-naphthalimide
      for recognition of pyrophosphate with ratiometrical fluorescence changes in
      aqueous solution has been synthesized and characterized. Its biological
      application to monitor the intracellular pyrophosphate (PPi) was successfully
      demonstrated by the observation that the fluorescence of 1 was enhanced by the
      presence of the Zn(2+) ion and was quenched by addition of PPi.

PMID- 21899306
TI  - Effect of aqueous Fe(II) on arsenate sorption on goethite and hematite.
AB  - Biogeochemical iron cycling often generates systems where aqueous Fe(II) and
      solid Fe(III) oxides coexist. Reactions between these species result in iron
      oxide surface and phase transformations, iron isotope fractionation, and redox
      transformations of many contaminant species. Fe(II)-induced recrystallization of
      goethite and hematite has recently been shown to cause the repartitioning of
      Ni(II) at the mineral-water interface, with adsorbed Ni incorporating into the
      iron oxide structure and preincorporated Ni released back into aqueous solution.
      However, the effect of Fe(II) on the fate and speciation of redox inactive
      species incompatible with iron oxide structures is unclear. Arsenate sorption to
      hematite and goethite in the presence of aqueous Fe(II) was studied to determine
      whether Fe(II) causes substantial changes in the sorption mechanisms of such
      incompatible species. Sorption isotherms reveal that Fe(II) minimally alters
      macroscopic arsenate sorption behavior except at circumneutral pH in the presence
      of elevated concentrations (10-3 M) of Fe(II) and at high arsenate loadings,
      where a clear signature of precipitation is observed. Powder X-ray diffraction
      demonstrates that the ferrous arsenate mineral symplesite precipitates under such
      conditions. Extended X-ray absorption fine structure spectroscopy shows that
      outside this precipitation regime arsenate surface complexation mechanisms are
      unaffected by Fe(II). In addition, arsenate was found to suppress Fe(II) sorption
      through competitive adsorption processes before the onset of symplesite
      precipitation. This study demonstrates that the sorption of species incompatible
      with iron oxide structure is not substantially affected by Fe(II) but that such
      species may potentially interfere with Fe(II)-iron oxide reactions via
      competitive adsorption.

PMID- 21899307
TI  - Infrared spectroscopic insight into hydration behavior of poly(N
      vinylcaprolactam) in water.
AB  - IR spectroscopy in combination with two-dimensional correlation spectroscopy
      (2DCOS) and the perturbation correlation moving window (PCMW) technique is
      employed to illustrate the dynamic hydration behavior of poly(N-vinylcaprolactam)
      (PVCL) in water, which exhibits a typical type I continuous lower critical
      solution temperature (LCST) behavior. PCMW easily determined the transition
      temperature to be ca. 43.5  degrees C during heating and ca. 42.5  degrees C
      during cooling and the transition temperature range to be 39.5-45  degrees C. On
      the other hand, 2DCOS was used to discern the sequence order of different species
      in PVCL and concluded that hydrogen bonding transformation predominates at the
      first stage below LCST while hydrophobic interaction predominates at the second
      stage above LCST. In combination with molecular dynamics simulation results, we
      find that there exists a distribution gradient of water molecules in PVCL
      mesoglobules ranging from a hydrophobic core to a hydrophilic surface. Due to the
      absence of self-associated hydrogen bonds and topological constraints, PVCL
      mesoglobules would form a "sponge-like" structure which can further continuously
      expel water molecules upon increasing temperature, while poly(N
      isopropylacrylamide) (PNIPAM) with self-associated hydrogen bonds forms
      mesoglobules with a "cotton-ball-like" structure without an apparent distribution
      gradient of water molecules and does not change much upon increasing temperature.

PMID- 21899304
TI  - Materials and transducers toward selective wireless gas sensing.

PMID- 21899308
TI  - Rapid and reproducible single-stage phosphopeptide enrichment of complex peptide
      mixtures: application to general and phosphotyrosine-specific phosphoproteomics
      experiments.
AB  - Reversible protein phosphorylation is an essential regulatory component of
      virtually every cellular process and is frequently dysregulated in cancer.
      However, significant analytical barriers persist that hamper the routine
      application of phosphoproteomics in translational settings. Here, we present a
      straightforward and reproducible approach for the broadscale analysis of protein
      phosphorylation that relies on a single phosphopeptide enrichment step using
      titanium dioxide microspheres from whole cell lysate digests and compared it to
      the well-established SCX-TiO(2) workflow for phosphopeptide purification on a
      proteome-wide scale. We demonstrate the scaleabilty of our approach from 200 MUg
      to 5 mg of total NCI-H23 non-small cell lung adenocarcinoma cell lysate digest
      and determine its quantitative reproducibility by label-free analysis of
      phosphopeptide peak areas from replicate purifications (median CV: 20% RSD).
      Finally, we combine this approach with immunoaffinity phosphotyrosine enrichment,
      enabling the identification of 3168 unique nonredundant phosphotyrosine peptides
      in two LC-MS/MS runs from 8 mg of HeLa peptides, each with 80% phosphotyrosine
      selectivity, at a peptide FDR of 0.2%. Taken together, we establish and validate
      a robust approach for proteome-wide phosphorylation analysis in a variety of
      scenarios that is easy to implement in biomedical research and translational
      settings.

PMID- 21899309
TI  - High-efficiency upconversion luminescent sensing and bioimaging of Hg(II) by
      chromophoric ruthenium complex-assembled nanophosphors.
AB  - A chromophoric ruthenium complex-assembled nanophosphor (N719-UCNPs) was achieved
      as a highly selective water-soluble probe for upconversion luminescence sensing
      and bioimaging of intracellular mercury ions. The prepared nanophosphors were
      characterized by X-ray powder diffraction (XRD), transmission electron microscopy
      (TEM), energy-dispersive X-ray analysis (EDXA), Fourier transform infrared
      spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). Further
      application of N719-UCNPs in sensing Hg(2+) was confirmed by optical titration
      experiment and upconversion luminescence live cell imaging. Using the ratiometric
      upconversion luminescence as a detection signal, the detection limit of Hg(2+)
      for this nanoprobe in water was down to 1.95 ppb, lower than the maximum level (2
      ppb) of Hg(2+) in drinking water set by the United States EPA. Importantly, the
      nanoprobe N719-UCNPs has been shown to be capable of monitoring changes in the
      distribution of Hg(2+) in living cells by upconversion luminescence bioimaging.

PMID- 21899310
TI  - Molecular weight effect on the formation of beta phase poly(9,9'-dioctylfluorene)
      in dilute solutions.
AB  - The effect of molecular weight on the formation of beta phase poly(9,9'
      dioctylfluorene) (PF8) was studied in dilute solutions. Temperature-dependent
      fluorescence experiments of unique synthetic batches as well as size-excluded
      single batches of polyflourene were studied. Each batch had unique molecular
      weight, tetrahedral defect concentration, and polydispersity index (PDI).
      Polyflourene was found to exhibit a temperature-dependent transition between two
      phases with distinct electronic transition signatures: the alpha (primary) phase
      and the beta (secondary) phase. In dilute solutions, the temperature at which the
      polymer exhibited a conversion between these phases showed a clear dependence on
      molecular weight. We model this transition temperature for beta phase formation
      using the mean field theory for the coil-globule transition developed by Isaac
      Sanchez. Results show that temperature affects the average end-to-end distance
      corresponding to increases in secondary electronic absorption and that the
      dependence on temperature related to the coil-globule transition.

PMID- 21899311
TI  - Pyrene-loaded polypyrrole microvessels.
AB  - The encapsulation of guest molecules within polymeric hollow nano- or microscale
      structures is a rapidly developing field of interdisciplinary research due to a
      variety of applications ranging from drug delivery and sensor fabrication to
      nanoscale synthesis and bioinspired mineralization. We report on the
      encapsulation of pyrene within three-dimensional polypyrrole microvessels
      synthesized by precipitation polymerization of pyrrole onto toluene droplets that
      contain pyrene. Steady state and time-resolved fluorescence measurements show
      that the optical response and dynamics of encapsulated pyrene is significantly
      different from that in the free solution, likely due to interactions with
      oligomeric species generated during the polymerization process that partition
      into the organic core of the microvessel. Our results indicate that the
      encapsulation process can have a significant influence on the local environment
      of encapsulated species, an issue that is critical from the perspective of
      potential synthetic or medical applications.

PMID- 21899312
TI  - Multiple equilibria interaction pattern between the ionic liquids C(n)mimPF6 and
      beta-cyclodextrin in aqueous solutions.
AB  - The interactions of ionic liquids (ILs) 1-alkyl-3-methylimidazolium
      hexafluorophosphate (C(n)mimPF(6), n = 2, 4, 6, 8) with beta-cyclodextrin (beta
      CD) in aqueous solutions are investigated in this article. The stoichiometry and
      apparent association constants were obtained by the competitive fluorescence
      method, NMR measurements, and isothermal titration calorimetry (ITC). The results
      showed that C(2)mimPF(6), C(4)mimPF(6), and C(6)mimPF(6) form 1:1 (guest:host)
      inclusion complexes with beta-CD whereas the 1:2 inclusion complex can be formed
      between C(8)mimPF(6) and beta-CD. We studied the existence state of the ILs and
      found that they exist mainly as separated ions with a minor percentage existing
      as associated ion pairs within the concentration studied. By ESI/HRMS, the
      coexistence of different complexes including C(n)mim(+).PF(6)(-)-beta-CD,
      C(n)mim(+)-beta-CD (or C(n)mim(+)-beta-CD(2)), and PF(6)(-)-beta-CD was observed.
      It is also deduced that the intermediate complex, (beta-CD-cation).(anion-beta
      CD), may dissociate into cation-beta-CD and anion-beta-CD complexes.
      Thermodynamic parameters determined by ITC indicate that, while the inclusion
      process for C(6)mimPF(6)/beta-CD complex is entropy and enthalpy driven, the
      interactions of other C(n)mimPF(6) (n = 2, 4, 8) with beta-CD are enthalpy
      controlled. Based on these results, a more comprehensive pattern involving
      multiple equilibria on the interaction between C(n)mimPF(6) and beta-CD in
      aqueous solutions is presented herein.

PMID- 21899313
TI  - Potent and selective inhibitors of glutathione S-transferase omega 1 that impair
      cancer drug resistance.
AB  - Glutathione S-transferases (GSTs) are a superfamily of enzymes that conjugate
      glutathione to a wide variety of both exogenous and endogenous compounds for
      biotransformation and/or removal. Glutathione S-tranferase omega 1 (GSTO1) is
      highly expressed in human cancer cells, where it has been suggested to play a
      role in detoxification of chemotherapeutic agents. Selective inhibitors of GSTO1
      are, however, required to test the role that this enzyme plays in cancer and
      other (patho)physiological processes. With this goal in mind, we performed a
      fluorescence polarization activity-based protein profiling (fluopol-ABPP) high
      throughput screen (HTS) with GSTO1 and the Molecular Libraries Small Molecule
      Repository (MLSMR) 300K+ compound library. This screen identified a class of
      selective and irreversible alpha-chloroacetamide inhibitors of GSTO1, which were
      optimized to generate an agent KT53 that inactivates GSTO1 with excellent in
      vitro (IC(50) = 21 nM) and in situ (IC(50) = 35 nM) potency. Cancer cells treated
      with KT53 show heightened sensitivity to the cytotoxic effects of cisplatin,
      supporting a role for GSTO1 in chemotherapy resistance.

PMID- 21899314
TI  - Optically definable reaction-diffusion-driven pattern generation of Ag-Au
      nanoparticles on templated surfaces.
AB  - We introduce a new lithographic method for the generation of 2D patterns of
      composite nanoparticles (NPs) of Ag and Au by taking recourse to combine top-down
      and bottom-up approaches. Micrometer-scale and submicrometer-scale patterned Ag
      foils of commercially available compact disks (CDs) and digital versatile disks
      (DVDs), respectively, were used as templates. The galvanic replacement reaction
      of Ag by HAuCl(4) in the presence of the dye coatings on the foils led to the
      formation of patterned NP composites of Ag and Au, in addition to the formation
      of AgCl. The resultant structures appeared in the form of cross patterns of
      particles with micrometer and submicrometer dimensions. The AgCl crystals thus
      formed could be removed by using either a saturated NaCl solution or aqueous
      ammonia. In addition, AgCl could be converted to Ag by electrochemical reduction,
      thus generating Ag-coated Au NPs. Interestingly, the digital writing on CDs led
      to the formation of tertiary imprints on the patterns, based on the original
      writing patterns. This provided an additional handle in generating hierarchical
      patterns using light in combination with a chemical reaction diffusion process
      and the nearly parallel line patterns originally present in commercial CDs. The
      reactions could be carried out in aqueous solution, and the method does not
      require any additional curing. Also, the density of patterned particles is
      scalable on the basis of the choice of the original line patterns as present in
      CDs and DVDs.

PMID- 21899315
TI  - Photoexcitation of the blue light using FAD photoreceptor AppA results in
      ultrafast changes to the protein matrix.
AB  - Photoexcitation of the flavin chromophore in the BLUF photosensor AppA results in
      a conformational change that leads to photosensor activation. This conformational
      change is mediated by a hydrogen-bonding network that surrounds the flavin, and
      photoexcitation is known to result in changes in the network that include a
      strengthening of hydrogen bonding to the flavin C4?O carbonyl group. Q63 is a key
      residue in the hydrogen-bonding network, and replacement of this residue with a
      glutamate results in a photoinactive mutant. While the ultrafast time-resolved
      infrared (TRIR) spectrum of Q63E AppA(BLUF) is characterized by flavin carbonyl
      modes at 1680 and 1650 cm(-1), which are similar in frequency to the analogous
      modes from the light activated state of the wild-type protein, a band is also
      observed in the TRIR spectrum at 1724 cm(-1) that is unambiguously assigned to
      the Q63E carboxylic acid based on U-(13)C labeling of the protein. Light
      absorption instantaneously (<100 fs) bleaches the 1724 cm(-1) band leading to a
      transient absorption at 1707 cm(-1). Because Q63E is not part of the
      isoalloxazine electronic transition, the shift in frequency must arise from a sub
      picosecond perturbation to the flavin binding pocket. The light-induced change in
      the frequency of the Q63E side chain is assigned to an increase in hydrogen-bond
      strength of 3 kcal mol(-1) caused by electronic reorganization of the
      isoalloxazine ring in the excited state, providing direct evidence that the
      protein matrix of AppA responds instantaneously to changes in the electronic
      structure of the chromophore and supporting a model for photoactivation of the
      wild-type protein that involves initial tautomerization of the Q63 side chain.

PMID- 21899316
TI  - Cofactor-free detection of phosphatidylserine with cyclic peptides mimicking
      lactadherin.
AB  - Cyclic peptides (cLacs) are designed to mimic the natural phosphatidylserine (PS)
      binding protein lactadherin. Unlike annexin V or its small molecule mimics, the
      cLac peptides selectively target PS-presenting membranes with no need for metal
      cofactors. We further show that a fluorophore-labeled cLac effectively stains
      early apoptotic cells. The small size and facile conjugation with a variety of
      imaging tracers make the cLac design promising for imaging cell death in vitro as
      well as in living organisms.

PMID- 21899317
TI  - Spectral response of 4-methyl-2,6-dicarbomethoxyphenol, an excited-state
      intramolecular proton-transfer probe in cyclohexane-ethanol mixtures: signatures
      of medium microheterogeneity.
AB  - In this paper, we explore the role of microscopic heterogeneity of the medium on
      the spectral response of an excited-state proton-transfer (ESIPT) probe, namely,
      4-methyl-2,6-dicarbomethoxyphenol (CMOH) using steady-state and time-resolved
      emission spectroscopy. The mixtures of two solvents with widely different
      properties, viz., cyclohexane, a nonpolar, and ethanol, a polar protic solvent,
      were used as microheterogeneous media for spectroscopic studies. Dual
      fluorescence (normal and tautomer fluorescence) is observed in the nonpolar
      solvent (cyclohexane), while only a single peak is observed in the protic
      solvent, ethanol. The spectral responses of CMOH in the binary mixtures have been
      found to be dependent on the solvent composition and excitation wavelength. The
      emission spectral properties of CMOH in the cyclohexane-ethanol mixture have been
      seen to be superposition of spectral properties in their bulk counterparts,
      indicating the presence of microscopic heterogeneity in the system. A
      zwitterionic species of CMOH appears to have been detected in binary solvent
      mixtures with higher ethanol content only through low-energy excitations. The
      species is converted into an anionic species as excitation energy increases.
      Density functional theory calculations indicate that two intramolecularly
      hydrogen bonded rotamers of CMOH have a small energy difference. The formation of
      a hydrogen bonded 1:1 molecular cluster of CMOH with ethanol has been
      investigated in the ground state at the same level of theory. Our findings are
      expected to shed light on the mechanism of many acid-base reactions occurring in
      microscopically inhomogeneous media that often mimic many biologically relevant
      processes.

PMID- 21899318
TI  - Nanoparticles targeting the infarcted heart.
AB  - We report a nanoparticulate system capable of targeting the heart after
      myocardial infarction (MI). Targeting is based on overexpression of angiotensin
      II type 1 (AT1) receptor in the infarcted heart. Liposomes 142 nm in diameter
      were conjugated with a ligand specific to AT1. The nanoparticles were able to
      specifically target cardiac cells in vitro, and in the infarcted heart after
      intravenous injection in vivo. This system may be useful for delivering
      therapeutic agents specifically to the infarcted heart.

PMID- 21899320
TI  - Toward local growth of individual nanowires on three-dimensional microstructures
      by using a minimally invasive catalyst templating method.
AB  - We present a novel minimally invasive postprocessing method for catalyst
      templating based on focused charged particle beam structuring, which enables a
      localized vapor-liquid-solid (VLS) growth of individual nanowires on
      prefabricated three-dimensional micro- and nanostructures. Gas-assisted focused
      electron beam induced deposition (FEBID) was used to deposit a SiO(x) surface
      layer of about 10 * 10 MUm(2) on top of a silicon atomic force microscopy
      cantilever. Gallium focused ion beam (FIB) milling was used to make a hole
      through the SiO(x) layer into the underlying silicon. The hole was locally filled
      with a gold catalyst via FEBID using either Me(2)Au(tfac) or Me(2)Au(acac) as
      precursor. Subsequent chemical vapor deposition (CVD)-induced VLS growth using a
      mixture of SiH(4) and Ar resulted in individual high quality crystalline
      nanowires. The process, its yield, and the resulting angular distribution/crystal
      orientation of the silicon nanowires are discussed. The presented combined
      FIB/FEBID/CVD-VLS process is currently the only proven method that enables the
      growth of individual monocrystalline Si nanowires on prestructured substrates and
      devices.

PMID- 21899319
TI  - Crystallographic snapshots of tyrosine phenol-lyase show that substrate strain
      plays a role in C-C bond cleavage.
AB  - The key step in the enzymatic reaction catalyzed by tyrosine phenol-lyase (TPL)
      is reversible cleavage of the Cbeta-Cgamma bond of L-tyrosine. Here, we present X
      ray structures for two enzymatic states that form just before and after the
      cleavage of the carbon-carbon bond. As for most other pyridoxal 5'-phosphate
      dependent enzymes, the first state, a quinonoid intermediate, is central for the
      catalysis. We captured this relatively unstable intermediate in the crystalline
      state by introducing substitutions Y71F or F448H in Citrobacter freundii TPL and
      briefly soaking crystals of the mutant enzymes with a substrate 3-fluoro-L
      tyrosine followed by flash-cooling. The X-ray structures, determined at ~2.0 A
      resolution, reveal two quinonoid geometries: "relaxed" in the open and "tense" in
      the closed state of the active site. The "tense" state is characterized by
      changes in enzyme contacts made with the substrate's phenolic moiety, which
      result in significantly strained conformation at Cbeta and Cgamma positions. We
      also captured, at 2.25 A resolution, the X-ray structure for the state just after
      the substrate's Cbeta-Cgamma bond cleavage by preparing the ternary complex
      between TPL, alanine quinonoid and pyridine N-oxide, which mimics the alpha
      aminoacrylate intermediate with bound phenol. In this state, the enzyme-ligand
      contacts remain almost exactly the same as in the "tense" quinonoid, indicating
      that the strain induced by the closure of the active site facilitates elimination
      of phenol. Taken together, structural observations demonstrate that the enzyme
      serves not only to stabilize the transition state but also to destabilize the
      ground state.

PMID- 21899321
TI  - Structure of the lycorinine alkaloid nobilisitine A.
AB  - The structure 3 recently proposed, on the basis of computed NMR chemical shifts,
      for the natural product nobilisitine A has been synthesized from its C5-epimer
      (+)-clividine (4). The spectral data derived from compound 3 match those reported
      for the natural product.

PMID- 21899322
TI  - Palladium catalyzed 1,8-conjugate addition to heptafulvene via bis-pi-allyl
      palladium complexes.
AB  - The palladium catalyzed 1,8-conjugate addition of heptafulvene, an antiaromatic
      conjugated 8pi-electron system, is discussed. The method is utilized for the
      concise synthesis of bis-functionalized cycloheptatriene (CHT) derivatives. This
      is the first report on the palladium catalyzed bisfunctionalization of a cyclic
      cross conjugated system.

PMID- 21899323
TI  - Single-molecule magnet behavior with a single metal center enhanced through
      peripheral ligand modifications.
AB  - Bis(imino)pyridine pincer ligands in conjunction with two isothiocyanate ligands
      have been used to prepare two mononuclear Co(II) complexes. Both complexes have a
      distorted square-pyramidal geometry with the Co(II) centers lying above the basal
      plane. This leads to significant spin-orbit coupling for the d(7) Co(II) ions and
      consequently to slow relaxation of the magnetization that is characteristic of
      Single-Molecule Magnet (SMM) behavior.

PMID- 21899324
TI  - Conjugation paths in monosubstituted 1,2- and 2,3-naphthoquinones.
AB  - Optimization of monosubstituted (X = NO, NO(2), CN, CHO, Me, OMe, OH, NH(2),
      NHMe, and N(Me)(2)) derivatives of 1,2- and 2,3-naphthoquinone by use of B3LYP
      with the 6-311+G** basis set applying the GAUSSIAN03 program allowed us to
      analyze the character of interactions between the substituents and the carbonyl
      groups. It is shown that only one of two carbonyl groups exhibited substantial
      substituent effect evidenced by regression of the CO bond length and
      delocalization index, DI(CO) on the Hammett substituent constants, sigma(p), with
      a very high correlation coefficient, whereas the other one did not depend in any
      substantial way on sigma(p). Dependences of conjugation path built up of bonds
      between substituent and oxygen atoms of carbonyl groups on sigma(p), give more
      acceptable correlations if the number of bonds in the path is even than in cases
      when they are odd.

PMID- 21899325
TI  - Three-dimensional nanobranched indium-tin-oxide anode for organic solar cells.
AB  - A nanostructured three-dimensional (3D) electrode using transparent conducting
      oxide (TCO) is an effective approach for increasing the efficiency of
      optoelectronic devices used in daily life. Tin-doped indium oxide (ITO) is a
      representative TCO with high conductivity and a high work function for anode
      applications. This paper reports the fabrication of a large-area ITO
      nanostructure with a branch shape using an electron beam evaporation process at
      temperatures as low as 80  degrees C, which was free of any carrier gas and
      catalyst. The large surface to volume ratio in the anode by the ITO nanobranches
      increases both the hole mobility by a 3D pathway and light absorbance by
      scattering, resulting in organic solar cells with a 12% increase in photocurrent
      and 20% photoconversion efficiency based on the bulk heterojunction of P3HT
      [region-regular poly(3-hexylthiophene)] and PCBM [phenyl-C61-butyric acid methyl
      ester].

PMID- 21899326
TI  - Inlet ionization: a new highly sensitive approach for liquid chromatography/mass
      spectrometry of small and large molecules.
AB  - Inlet ionization is a new approach for ionizing both small and large molecules in
      solids or liquid solvents with high sensitivity. The utility of solvent based
      inlet ionization mass spectrometry (MS) as a method for analysis of volatile and
      nonvolatile compounds eluting from a liquid chromatography (LC) column is
      demonstrated. This new LC/MS approach uses reverse phase solvent systems common
      to electrospray ionization MS. The first LC/MS analyses using this novel approach
      produced sharp chromatographic peaks and good quality full mass range mass
      spectra for over 25 peptides from injection of only 1 pmol of a tryptic digest of
      bovine serum albumin using an eluent flow rate of 55 MUL min(-1). Similarly, full
      acquisition LC/MS/MS of the MH(+) ion of the drug clozapine, using the same
      solvent flow rate, produced a signal-to-noise ratio of 54 for the major fragment
      ion with injection of only 1 MUL of a 2 ppb solution. LC/MS results were acquired
      on two different manufacturer's mass spectrometers using a Waters Corporation
      NanoAcquity liquid chromatograph.

PMID- 21899327
TI  - Selective CO2 conversion to formate conjugated with H2O oxidation utilizing
      semiconductor/complex hybrid photocatalysts.
AB  - Photoelectrochemical reduction of CO(2) to HCOO(-) (formate) over p-type InP/Ru
      complex polymer hybrid photocatalyst was highly enhanced by introducing an
      anchoring complex into the polymer. By functionally combining the hybrid
      photocatalyst with TiO(2) for water oxidation, selective photoreduction of CO(2)
      to HCOO(-) was achieved in aqueous media, in which H(2)O was used as both an
      electron donor and a proton source. The so-called Z-scheme (or two-step
      photoexcitation) system operated with no external electrical bias. The
      selectivity for HCOO(-) production was >70%, and the conversion efficiency of
      solar energy to chemical energy was 0.03-0.04%.

PMID- 21899328
TI  - Azaxanthene based selective glucocorticoid receptor modulators: design,
      synthesis, and pharmacological evaluation of (S)-4-(5-(1-((1,3,4-thiadiazol-2
      yl)amino)-2-methyl-1-oxopropan-2-yl)-5H-chromeno[2,3-b]pyridin-2-yl)-2-fluoro-N,N
      dimethylbenzamide (BMS-776532) and its methylene homologue (BMS-791826).
AB  - Structurally novel 5H-chromeno[2,3-b]pyridine (azaxanthene) selective
      glucocorticoid receptor (GR) modulators have been identified. A screening
      paradigm utilizing cellular assays of GR-mediated transrepression of
      proinflammatory transcription factors and transactivation of GR-dependent genes
      combined with three physiologically relevant assays of cytokine induction in
      human whole blood has allowed for the identification of high affinity, selective
      GR ligands that display a broad range of pharmacological profiles. Agonist
      efficacy in reporter assays can be tuned by halogenation of a pendent phenyl ring
      and correlates well with efficacy for cytokine inhibition in human whole blood. A
      hypothetical binding mode is proposed, invoking an expanded ligand binding pocket
      resembling that of arylpyrazole-bound GR structures. Two compounds of close
      structural similarity (35 and 37; BMS-776532 and BMS-791826, respectively) have
      been found to maintain distinct and consistent levels of partial agonist efficacy
      across several assays, displaying anti-inflammatory activity comparable to that
      of prednisolone 2 in suppressing cytokine production in whole blood and in rodent
      models of acute and chronic inflammation.

PMID- 21899330
TI  - An interfacial and bulk charge transport model for dye-sensitized solar cells
      based on photoanodes consisting of core-shell nanowire arrays.
AB  - Dye-sensitized solar cells (DSSCs) based on ordered photoanode morphologies, such
      as nanotubes and nanowires, are widely gaining attention because these geometries
      are believed to enhance interfacial charge transfer and bulk charge transport.
      Unfortunately, experimental results have yet to show substantial improvement to
      conversion efficiency over nanoparticle-based DSSCs. A model is developed to
      characterize the performance of an idealized photoanode based on an ordered array
      of transparent conductive nanowires coated with an anatase titania shell. The
      role of the interfacial electric field in nanowire-based DSSCs is explored
      computationally by turning electron migration ON or OFF. The results show that
      back-reaction rates are most strongly influenced by the electric field. These
      electron loss mechanisms can be reduced by several orders of magnitude, leading
      to improvements in short-circuit current, open-circuit voltage, and fill factor.

PMID- 21899329
TI  - Single-molecule detection of H2O2 mediating angiogenic redox signaling on
      fluorescent single-walled carbon nanotube array.
AB  - Reactive oxygen species, specifically hydrogen peroxide (H(2)O(2)), activate
      signal transduction pathways during angiogenesis and therefore play an important
      role in physiological development as well as various pathophysiologies. Herein,
      we utilize a near-infrared fluorescent single-walled carbon nanotube (SWNT)
      sensor array to measure the single-molecule efflux of H(2)O(2) from human
      umbilical vein endothelial cells (HUVEC) in response to angiogenic stimulation.
      Two angiogenic agents were investigated: the pro-angiogenic cytokine, vascular
      endothelial growth factor A (VEGF-A) and the recently identified inorganic pro
      angiogenic factor, europium(III) hydroxide in nanorod form. The nanosensor array
      consists ofa SWNT embedded within a collagen matrix that exhibits high
      selectivity and sensitivity to single molecules of H(2)O(2). A calibration from
      12.5 to 400 nM quantifies the production of H(2)O(2) at nanomolar concentration
      in HUVEC with 1 s temporal and 300 nm spatial resolutions. We find that the
      production of H(2)O(2) following VEGF stimulation is elevated outside of HUVEC,
      but not for stimulation via nanorods, while increased generation is observed in
      the cytoplasm for both cases, suggesting two distinct signaling pathways.

PMID- 21899331
TI  - Rational domain swaps decipher programming in fungal highly reducing polyketide
      synthases and resurrect an extinct metabolite.
AB  - The mechanism of programming of iterative highly reducing polyketide synthases
      remains one of the key unsolved problems of secondary metabolism. We conducted
      rational domain swaps between the polyketide synthases encoding the biosynthesis
      of the closely related compounds tenellin and desmethylbassianin. Expression of
      the hybrid synthetases in Aspergillus oryzae led to the production of
      reprogrammed compounds in which the changes to the methylation pattern and chain
      length could be mapped to the domain swaps. These experiments reveal for the
      first time the origin of programming in these systems. Domain swaps combined with
      coexpression of two cytochrome P450 encoding genes from the tenellin biosynthetic
      gene cluster led to the resurrection of the extinct metabolite bassianin.

PMID- 21899332
TI  - P1-substituted symmetry-based human immunodeficiency virus protease inhibitors
      with potent antiviral activity against drug-resistant viruses.
AB  - Because there is currently no cure for HIV infection, patients must remain on
      long-term drug therapy, leading to concerns over potential drug side effects and
      the emergence of drug resistance. For this reason, new and safe antiretroviral
      agents with improved potency against drug-resistant strains of HIV are needed. A
      series of HIV protease inhibitors (PIs) with potent activity against both wild
      type (WT) virus and drug-resistant strains of HIV was designed and synthesized.
      The incorporation of substituents with hydrogen bond donor and acceptor groups at
      the P1 position of our symmetry-based inhibitor series resulted in significant
      potency improvements against the resistant mutants. By this approach, several
      compounds, such as 13, 24, and 29, were identified that demonstrated similar or
      improved potencies compared to 1 against highly mutated strains of HIV derived
      from patients who previously failed HIV PI therapy. Overall, compound 13
      demonstrated the best balance of potency against drug resistant strains of HIV
      and oral bioavailability in pharmacokinetic studies. X-ray analysis of an HIV PI
      with an improved resistance profile bound to WT HIV protease is also reported.

PMID- 21899333
TI  - Multiscale-tailored bioelectrode surfaces for optimized catalytic conversion
      efficiency.
AB  - We describe the elaboration of a multiscale-tailored bioelectrocatalytic system.
      The combination of two enzymes, D-sorbitol dehydrogenase and diaphorase, is
      studied with respect to the oxidation of D-sorbitol as a model system. The
      biomolecules are immobilized in an electrodeposited paint (EDP) layer.
      Reproducible and efficient catalysis of D-sorbitol oxidation is recorded when
      this system is immobilized on a gold electrode modified by a self-assembled
      monolayer of 4-carboxy-(2,5,7-trinitro-9-fluorenylidene)malonitrile used as a
      mediator. The insertion of mediator-modified gold nanoparticles into the EDP film
      increases significantly the active surface area for the catalytic reaction, which
      can be further enhanced when the whole system is immobilized in macroporous gold
      electrodes. This multiscale architecture finally leads to a catalytic device with
      optimized efficiency for potential use in biosensors, bioelectrosynthesis, and
      biofuel cells.

PMID- 21899334
TI  - Evaluation of the deuterium isotope effect in zwitterionic hydrophilic
      interaction liquid chromatography separations for implementation in a
      quantitative proteomic approach.
AB  - Quantitative methodologies for the global in-depth comparison of proteomes are
      frequently based on chemical derivatization of peptides with isotopically
      distinguishable labeling agents. In the present work, we set out to study the
      feasibility of the dimethyl labeling method in combination with ZIC-cHILIC
      (zwitterionic hydrophilic interaction liquid chromatography) technology for
      quantitative proteomics. We first addressed the potential issue of isotope
      effects perturbing the essential coelution of differently labeled peptides under
      ZIC-cHILIC separation. The deuterium incorporation-induced effect can be largely
      eliminated by favoring the mixed-mode ZIC-cHILIC separation based on combined
      hydrophilic and ionic interactions. Then, we evaluated the performance and
      applicability of this strategy using a sample consisting of human cell lysate. We
      demonstrate that our approach is suitable to perform unbiased quantitative
      proteome analysis, still quantifying more than 2500 proteins when analyzing only
      a few micrograms of sample.

PMID- 21899335
TI  - Improved tumor targeting of polymer-based nanovesicles using polymer-lipid
      blends.
AB  - Block copolymer-based vesicles have recently garnered a great deal of interest as
      nanoplatforms for drug delivery and molecular imaging applications due to their
      unique structural properties. These nanovesicles have been shown to direct their
      cargo to disease sites either through enhanced permeability and retention or even
      more efficiently via active targeting. Here, we show that the efficacy of
      nanovesicle targeting can be significantly improved when prepared from polymer
      lipid blends compared with block copolymer alone. Polymer-lipid hybrid
      nanovesicles were produced from the aqueous coassembly of the diblock copolymer,
      poly(ethylene oxide)-block-polybutadiene (PEO-PBD), and the phospholipid,
      hydrogenated soy phosphatidylcholine (HSPC). The PEG-based vesicles, 117 nm in
      diameter, were functionalized with either folic acid or anti-HER2/neu affibodies
      as targeting ligands to confer specificity for cancer cells. Our results revealed
      that nanovesicles prepared from polymer-lipid blends led to significant
      improvement in cell binding compared to nanovesicles prepared from block
      copolymer alone in both in vitro cell studies and murine tumor models. Therefore,
      it is envisioned that nanovesicles composed of polymer-lipid blends may
      constitute a preferred embodiment for targeted drug delivery and molecular
      imaging applications.

PMID- 21899336
TI  - Substrate-triggered activation of a synthetic [Fe2(MU-O)2] diamond core for C-H
      bond cleavage.
AB  - An [Fe(IV)(2)(MU-O)(2)] diamond core structure has been postulated for
      intermediate Q of soluble methane monooxygenase (sMMO-Q), the oxidant responsible
      for cleaving the strong C-H bond of methane and its hydroxylation. By extension,
      analogous species may be involved in the mechanisms of related diiron
      hydroxylases and desaturases. Because of the paucity of well-defined synthetic
      examples, there are few, if any, mechanistic studies on the oxidation of
      hydrocarbon substrates by complexes with high-valent [Fe(2)(MU-O)(2)] cores. We
      report here that water or alcohol substrates can activate synthetic
      [Fe(III)Fe(IV)(MU-O)(2)] complexes supported by tetradentate tris(pyridyl-2
      methyl)amine ligands (1 and 2) by several orders of magnitude for C-H bond
      oxidation. On the basis of detailed kinetic studies, it is postulated that the
      activation results from Lewis base attack on the [Fe(III)Fe(IV)(MU-O)(2)] core,
      resulting in the formation of a more reactive species with a [X-Fe(III)-O
      Fe(IV)?O] ring-opened structure (1-X, 2-X, X = OH(-) or OR(-)). Treatment of 2
      with methoxide at -80  degrees C forms the 2-methoxide adduct in high yield,
      which is characterized by an S = 1/2 EPR signal indicative of an
      antiferromagnetically coupled [S = 5/2 Fe(III)/S = 2 Fe(IV)] pair. Even at this
      low temperature, the complex undergoes facile intramolecular C-H bond cleavage to
      generate formaldehyde, showing that the terminal high-spin Fe(IV)?O unit is
      capable of oxidizing a C-H bond as strong as 96 kcal mol(-1). This intramolecular
      oxidation of the methoxide ligand can in fact be competitive with intermolecular
      oxidation of triphenylmethane, which has a much weaker C-H bond (D(C-H) 81 kcal
      mol(-1)). The activation of the [Fe(III)Fe(IV)(MU-O)(2)] core is dramatically
      illustrated by the oxidation of 9,10-dihydroanthracene by 2-methoxide, which has
      a second-order rate constant that is 3.6 * 10(7)-fold larger than that for the
      parent diamond core complex 2. These observations provide strong support for the
      DFT-based notion that an S = 2 Fe(IV)?O unit is much more reactive at H-atom
      abstraction than its S = 1 counterpart and suggest that core isomerization could
      be a viable strategy for the [Fe(IV)(2)(MU-O)(2)] diamond core of sMMO-Q to
      selectively attack the strong C-H bond of methane in the presence of weaker C-H
      bonds of amino acid residues that define the diiron active site pocket.

PMID- 21899338
TI  - Synthesis of titania-silica core-shell microspheres via a controlled interface
      reaction in a microfluidic device.
AB  - In this work, we describe a novel, simple microfluidic method for fabricating
      titania-silica core-shell microspheres. Uniform droplets of silica sol were
      dispersed into an oil phase containing tetrabutyl titanate via a coaxial
      microfluidic device. The titanium alkoxide hydrolyzed at the water-oil interface
      after the formation of the aqueous droplets. A gel shell containing the titanium
      hydroxide formed around the droplets, and the titania-silica core-shell
      microspheres were obtained after calcinations. The X-ray diffraction results show
      that titania coatings crystallized into a pure anatase structure. The scanning
      electron microscopy and energy-dispersive spectrometry characterization shows
      that the microspheres are monodispersed with uniform titania coating on the
      surface. The dispersity and size of the microspheres could easily be controlled
      by changing the microfluidic flow parameters. The titania content on the surface
      could be adjusted in the large range of 1.0-98.0 mol % by varying the continuous
      phase composition and the reaction time, and the structures of the core-shell
      microshperes could also be controlled.

PMID- 21899339
TI  - Contact-independent measurement of electrical conductance of a thin film with a
      nanoscale sensor.
AB  - Contact effects are a common impediment to electrical measurements throughout the
      fields of nanoelectronics, organic electronics, and the emerging field of
      graphene electronics. We demonstrate a novel method of measuring electrical
      conductance in a thin film of amorphous germanium that is insensitive to contact
      effects. The measurement is based on the capacitive coupling of a nanoscale metal
      oxide-semiconductor field-effect transistor (MOSFET) to the thin film so that the
      MOSFET senses charge diffusion in the film. We tune the contact resistance
      between the film and contact electrodes and show that our measurement is
      unaffected. With the MOSFET, we measure the temperature and field dependence of
      the conductance of the amorphous germanium, which are fit to a model of variable
      range hopping. The device structure enables both a contact-independent and a
      conventional, contact-dependent measurement, which makes it possible to discern
      the effect of the contacts in the latter measurement. This measurement method can
      be used for reliable electrical characterization of new materials and to
      determine the effect of contacts on conventional electron transport measurements,
      thus guiding the choice of optimal contact materials.

PMID- 21899337
TI  - Elucidating the energetics of entropically driven protein-ligand association:
      calculations of absolute binding free energy and entropy.
AB  - The binding of proteins and ligands is generally associated with the loss of
      translational, rotational, and conformational entropy. In many cases, however,
      the net entropy change due to binding is positive. To develop a deeper
      understanding of the energetics of entropically driven protein-ligand binding, we
      calculated the absolute binding free energies and binding entropies for two HIV-1
      protease inhibitors Nelfinavir and Amprenavir using the double-decoupling method
      with molecular dynamics simulations in explicit solvent. For both ligands, the
      calculated absolute binding free energies are in general agreement with
      experiments. The statistical error in the computed DeltaG(bind) due to
      convergence problem is estimated to be >=2 kcal/mol. The decomposition of free
      energies indicates that, although the binding of Nelfinavir is driven by nonpolar
      interaction, Amprenavir binding benefits from both nonpolar and electrostatic
      interactions. The calculated absolute binding entropies show that (1) Nelfinavir
      binding is driven by large entropy change and (2) the entropy of Amprenavir
      binding is much less favorable compared with that of Nelfinavir. Both results are
      consistent with experiments. To obtain qualitative insights into the entropic
      effects, we decomposed the absolute binding entropy into different contributions
      based on the temperature dependence of free energies along different legs of the
      thermodynamic pathway. The results suggest that the favorable entropic
      contribution to binding is dominated by the ligand desolvation entropy. The
      entropy gain due to solvent release from binding site appears to be more than
      offset by the reduction of rotational and vibrational entropies upon binding.

PMID- 21899340
TI  - Size-selective enrichment of N-linked glycans using highly ordered mesoporous
      carbon material and detection by MALDI-TOF MS.
AB  - Many diseases are characterized by the changes of either glycan structure or
      glycosylation site of glycoproteins. The glycan profiling can provide the
      overview of glycosylation in despite of the absence of the glycosylation sites,
      which in turn simplifies the complexity of disease diagnosis. Herein, we describe
      a simple method to profile the N-linked glycans by MALDI-TOF MS with the
      enrichment using oxidized ordered mesoporous carbon, taking advantages of the
      size-exclusive effect of mesopore against proteins as well as the interaction
      between glycans and carbon. Twenty four N-linked glycans derived from ovalbumin
      could be efficiently detected with high signal-to-noise (S/N) ratios and
      sufficient peak intensities. In the analysis of complex serum samples, 32 N
      linked glycans could be profiled, and 5 (4 core-fucosylated glycans) of them were
      distinguished from liver cancer and healthy samples.

PMID- 21899341
TI  - Hydrodynamic forces and critical stresses in low-density aggregates under shear
      flow.
AB  - The distribution of stresses in rigid colloidal aggregates under a shear flow was
      investigated numerically for particle-cluster and cluster-cluster aggregates with
      fractal dimensions ranging from 1.7 to 2.3. stokesian dynamics was used to
      calculate the hydrodynamic force on each monomer, while the internal intermonomer
      interactions were calculated by applying force and torque balances on each
      primary particle. Although the hydrodynamic forces act mainly on the periphery of
      the clusters, their filamentous structure propagates and accumulates internal
      stresses toward the inner region of the aggregates, where consequently the most
      loaded intermonomer bonds are located. The spatial stress distribution, when
      scaled by the proper power of the radius of gyration, is independent of aggregate
      size and fractal dimension. This feature has made it possible to identify the
      most probable locations of bond failure in the structure and to estimate the
      relationship between shear rate and particle size for the occurrence of
      restructuring and of breakage.

PMID- 21899342
TI  - Electronic double slit interferometers based on carbon nanotubes.
AB  - We report the realization of an electronic double slit interferometer based on
      individual carbon nanotubes (SWNT). By performing transport spectroscopy on two
      parallel SWNTs in close proximity, we observe superposition of conductance
      oscillation with two different frequencies, "inverse" Coulomb blockade patterns,
      and Fano-like line-shapes with abrupt phase shifts. These features arise from
      coherent interference of electrons that traverse two conduction channels with
      significantly different transmission coefficients, underscoring the potential of
      SWNT for on-chip realization of electron optics.

PMID- 21899344
TI  - G4-DNA-coated gold nanoparticles: synthesis and assembly.
AB  - Here, we describe the preparation of stable 15 nm gold nanoparticles (Au-NPs)
      coated with parallel-stranded G-quadruplexes (G4-DNA), comprising
      phosphorothioate residues on both sides of the DNA. Phosphorothioate residues
      located on the surface of the coated particles can anchor them to noncoated ones.
      Their incubation with more than 20-fold excess of 15 nm citrate-stabilized Au-NPs
      leads to the formation of flower-shaped structures comprising a central noncoated
      particle and five to six G-quadruplex-coated ones at the periphery, as revealed
      by TEM imaging analysis. The absorption band of the structures is shifted toward
      long wavelengths compared to individual particles not connected to each other. We
      show a strong dependence of plasmon coupling strength on the length of the DNA
      connecting Au-NPs.

PMID- 21899345
TI  - Bioreducible block copolymers based on poly(ethylene glycol) and poly(gamma
      benzyl L-glutamate) for intracellular delivery of camptothecin.
AB  - Poly(ethylene glycol)-b-poly(gamma-benzyl L-glutamate)s bearing the disulfide
      bond (PEG-SS-PBLGs), which is specifically cleavable in intracellular
      compartments, were prepared via a facile synthetic route as a potential carrier
      of camptothecin (CPT). Diblock copolymers with different lengths of PBLG were
      synthesized by ring-opening polymerization of benzyl glutamate N-carboxy
      anhydride in the presence of a PEG macroinitiator (PEG-SS-NH(2)). Owing to their
      amphiphilic nature, the copolymers formed spherical micelles in an aqueous
      condition, and their particle sizes (20-125 nm in diameter) were dependent on the
      block length of PBLG. Critical micelle concentrations of the copolymers were in
      the range 0.005-0.065 mg/mL, which decreased as the block length of PBLG
      increased. CPT, chosen as a model anticancer drug, was effectively encapsulated
      up to 12 wt % into the hydrophobic core of the micelles by the solvent casting
      method. It was demonstrated by the in vitro optical imaging technique that the
      fluorescence signal of doxorubicin, quenched in the PEG-SS-PBLG micelles, was
      highly recovered in the presence of glutathione (GSH), a tripeptide reducing
      disulfide bonds in the cytoplasm. The micelles released CPT completely within 20
      h under 10 mM GSH, whereas only 40% of CPT was released from the micelles in the
      absence of GSH. From the in vitro cytotoxicity test, it was found that CPT-loaded
      PEG-SS-PBLG micelles showed higher toxicity to SCC7 cancer cells than CPT-loaded
      PEG-b-PBLG micelles without the disulfide bond. Microscopic observation
      demonstrated that the disulfide-containing micelle could effectively deliver the
      drug into nuclei of SCC7 cells. These results suggest that PEG-SS-PBLG diblock
      copolymer is a promising carrier for intracellular delivery of CPT.

PMID- 21899343
TI  - Histone deacetylase inhibitors: emerging mechanisms of resistance.
AB  - The histone deacetylase inhibitors (HDIs) have shown promise in the treatment of
      a number of hematologic malignancies, leading to the approval of vorinostat and
      romidepsin for the treatment of cutaneous T-cell lymphoma and romidepsin for the
      treatment of peripheral T-cell lymphoma by the U.S. Food and Drug Administration.
      Despite these promising results, clinical trials with the HDIs in solid tumors
      have not met with success. Examining mechanisms of resistance to HDIs may lead to
      strategies that increase their therapeutic potential in solid tumors. However,
      relatively few examples of drug-selected cell lines exist, and mechanisms of
      resistance have not been studied in depth. Very few clinical translational
      studies have evaluated resistance mechanisms. In the current review, we summarize
      many of the purported mechanisms of action of the HDIs in clinical trials and
      examine some of the emerging resistance mechanisms.

PMID- 21899346
TI  - MicroRNA expression profiles associated with development of drug resistance in
      Ehrlich ascites tumor cells.
AB  - Multidrug resistance (MDR) poses a major obstacle to successful chemotherapeutic
      treatment of cancer, and often involves multiple genes, which may be regulated
      post-transcriptionally by microRNAs (miRNAs). The purpose of the present study
      was therefore to identify any resistance-associated changes in miRNA expression
      in a sensitive and five increasingly drug-resistant Ehrlich ascites tumor (EAT)
      cell lines, representing different steps in the development of resistance. We
      used an LNA-enhanced microarray platform to study the global miRNA expression
      profiles in the six murine EAT cell lines, and identified growth-, hypoxia-, and
      resistance-specific miRNA patterns. Among the differentially expressed miRNAs, we
      found the two clusters miR-183~miR-96~miR-182 and miR-200b~miR-200a~miR-429 as
      well as miR-141 to be consistently upregulated in the MDR cell lines, while miR
      125b-5p and the two clusters miR-30d~miR-30b and miR-23b~miR-27b~miR-24-1 were
      downregulated in most of the resistant EAT cells. Several of the target genes for
      these miRNAs-including Zeb1/Zeb2 and members of the Fox gene family-could
      contribute to the drug-resistant phenotype, although we did not find that the
      degree of resistance was directly correlated to any specific changes in miRNA
      expression. Probably, the observed miRNA expression patterns reflect the
      underlying genomic instability of the tumor cells, and further studies are needed
      to explore how the highly complex regulatory miRNA networks contribute to the
      development of MDR.

PMID- 21899347
TI  - Observation of Raman g-peak split for graphene nanoribbons with hydrogen
      terminated zigzag edges.
AB  - Raman scattering of individual hydrogen-terminated zigzag-edged graphene
      nanoribbons (Z-GNRs) was studied with focus on the G-peak. In addition to the
      bulk graphene G-peak appearing at ~1594 cm(-1) (G(+)), an edge-related G-peak at
      ~1583 cm(-1) (G(-)) was observed for Z-GNRs. This additional Raman vibrational
      mode originates from the zigzag edges where localized metallic edge states are
      present. The relative intensity ratio G(-)/G(+) displays a strong dependence on
      the ribbon width (W). It increases gradually with decreasing W, and the G(+)
      finally vanishes at W = 5(+/-3) nm. Polarized Raman scattering was also employed
      to confirm the four-fold symmetry of the split TO modes, and the results are in
      good agreement with previous theoretical predictions. Our work offers the first
      direct experimental evidence to confirm the validity of predicted Raman
      scattering of GNRs.

PMID- 21899348
TI  - Synthesis and characterization of wurtzite ZnTe nanorods with controllable aspect
      ratios.
AB  - ZnTe nanorods with controllable aspect ratios were synthesized using
      polytellurides a tellurium precursor. The use of polytellurides which allow
      nucleation and growth at relatively low temperature is the key to formation of
      wurtzite phase and controlled anisotropic growth along c-axis. The aspect ratio
      of the resulting ZnTe nanorods was controlled by tuning the temperature that in
      turn controls the kinetics of the nanocrystal growth. A diameter dependent
      quantum confinement effect in ZnTe nanorods was observed by UV-vis absorption
      spectroscopy. Transient absorption measurements show ultrafast charge injection
      dynamics from ZnTe nanorods, suggesting their strong potential for applications
      in photocatalysis.

PMID- 21899350
TI  - Exploring the strength, mode, dynamics, and kinetics of binding interaction of a
      cationic biological photosensitizer with DNA: implication on dissociation of the
      drug-DNA complex via detergent sequestration.
AB  - The present study aims at exploring a detailed characterization of the binding
      interaction of a promising cancer cell photosensitizer, harmane (HM), with DNA
      extracted from herring sperm. The polarity-sensitive prototropic transformation
      of HM, a naturally occurring, fluorescent, drug-binding alkaloid, beta-carboline,
      is remarkably modified upon interaction with DNA and is manifested through
      significant modulations on the absorption and emission profiles of HM. From the
      series of studies undertaken in the present program, for example, absorption;
      steady-state emission; the effect of chaotrope (urea); iodide ion-induced steady
      state fluorescence quenching; circular dichroism (CD); and helix melting from
      absorption spectroscopy; the mode of binding of HM into the DNA helix has been
      substantiated to be principally intercalative. Concomitantly, a discernible
      dependence of the photophysics of the DNA-bound drug on the medium ionic strength
      indicates that electrostatic attraction should not be ignored in the interaction.
      Efforts have also been delivered to delineate the dynamical aspects of the
      interaction, such as modulation in time-resolved fluorescence decay and
      rotational relaxation dynamics of the drug within the DNA environment. In view of
      the prospective biological applications of HM, the issue of facile dissociation
      of intercalated HM from the DNA helix also comprises a crucial prerequisite for
      the functioning as an effective therapeutic agent. In this context, our results
      imply that the concept of detergent-sequestered dissociation of the drug from the
      drug-DNA complex can be a prospective strategy through an appropriate choice of
      the detergent molecule. The utility of the present work resides in exploring the
      potential applicability of the fluorescence property of HM for studying its
      interactions with a relevant biological target, for example, DNA. In addition,
      the methods and techniques used in the present work can also be exploited to
      study the interaction of HM with other biological, biomimicking assemblies and
      drug delivery vehicles, and so forth.

PMID- 21899349
TI  - Synthesis, structure, and biological activity of dumbbell-shaped nanocircular
      RNAs for RNA interference.
AB  - RNA interference (RNAi) is one of the most promising new approaches for disease
      therapy. The design of a dumbbell-shaped nanocircular RNA allows it to act as a
      short interfering RNA (siRNA) precursor. To optimize the design, we studied the
      relationship between the nanostructure and RNAi activity by synthesizing various
      RNA dumbbells. An RNA dumbbell with a 23-bp stem and 9-nt loops was the most
      potent. Sequence analysis by mass spectrometry showed that Dicer could edit RNA
      dumbbells to siRNA species. The reaction offered the slow release of siRNA
      species, which conferred prolonged RNAi activity. Introduction of DNA into the
      loop position significantly stabilized the dumbbell in biological fluid without
      any loss of RNAi activity. In-depth pharmacological evaluation was performed by
      introducing dumbbells into HeLa cells that stably express the target luciferase
      gene. The dumbbells provided a rapid silencing effect and retained this effect
      for a longer time even at a lower concentration than that at which standard siRNA
      completely lost RNAi activity. We conclude that an RNA dumbbell with DNA loops is
      the most promising design for in vivo applications for RNA medicine.

PMID- 21899351
TI  - Novel strategy for microsphere-mediated DNA transfection.
AB  - A new approach for microsphere-mediated delivery of plasmid DNA has been
      developed and successfully evaluated. Basic molecular biology techniques were
      used to linearize and functionalize plasmid DNA by aminomodification, enabling
      efficient conjugation to carboxy-functionalized microspheres. A T cell hybridoma
      line was successfully transfected as determined by the efficient expression of a
      biologically relevant YFP fusion protein. Moreover, our data identified
      microsphere-mediated delivery of plasmid DNA as a noninvasive, nontoxic, and
      efficient gene delivery method with the potential to be applied to transfection
      resistant, nondividing primary cells, including naive T cells.

PMID- 21899352
TI  - Multimerized siRNA cross-linked by gold nanoparticles.
AB  - In this study, siRNAs terminated with thiol groups were multimerized and cross
      linked using ~5 nm gold nanoparticles (AuNPs) via Au-S chemisorption that can be
      intracellularly reduced. AuNPs immobilized with single-stranded antisense siRNA
      were assembled with those with single-stranded sense siRNA via complementary
      hybridization or assembled with those with single-stranded dimeric sense siRNA.
      The multimerized siRNA cross-linked by AuNPs showed increased charge density and
      enhanced enzymatic stability, and exhibited good complexation behaviors with a
      polycationic carrier, linear polyethylenimine (L-PEI). The resultant multi
      siRNA/AuNPs/L-PEI polyelectrolyte complexes exhibited far greater gene silencing
      efficiencies of green fluorescent protein (GFP) and vascular endothelial growth
      factor (VEGF) compared to naked siRNA complexes. They could also be visualized by
      micro-CT imaging. The results suggest that AuNP-mediated multimerization of
      siRNAs could be a rational approach to achieve both gene silencing and imaging at
      a target tissue simultaneously.

PMID- 21899353
TI  - alpha-Conotoxin ImI incorporating stable cystathionine bridges maintains full
      potency and identical three-dimensional structure.
AB  - The two disulfide bonds of alpha-conotoxin ImI, a peptide antagonist of the
      alpha7 nicotinic acetylcholine receptor (nAChR), were systematically replaced
      with isosteric redox-stable cystathionine thioethers. Regioselective thioether
      formation was accomplished on solid support through substitution of a gamma
      chlorohomoalanine by an intramolecular cysteine thiol to produce hybrid
      thioether/disulfide analogues (2 and 3) as well as a dual cystathionine analogue
      (4) that were found to be structurally homologous to alpha-conotoxin ImI by (1)H
      NMR. The antagonistic activity at the alpha7 nAChR of cystathionine analogue 3
      (pIC(50) = 6.41 +/- 0.09) was identical to that of alpha-conotoxin ImI (1,
      pIC(50) = 6.41 +/- 0.09), whereas those of 2 (pIC(50) = 5.96 +/- 0.09) and 4
      (pIC(50) = 5.89 +/- 0.09) showed a modest decrease. The effect of oxidation of
      the thioethers to sulfoxides was also investigated, with significant changes in
      the biological activities observed ranging from a >30-fold reduction (2S?O) to a
      3-fold increase (3S?O(B)) in potencies.

PMID- 21899354
TI  - Unified molecular view of the air/water interface based on experimental and
      theoretical chi(2) spectra of an isotopically diluted water surface.
AB  - The energetically unfavorable termination of the hydrogen-bonded network of water
      molecules at the air/water interface causes molecular rearrangement to minimize
      the free energy. The long-standing question is how water minimizes the surface
      free energy. The combination of advanced, surface-specific nonlinear spectroscopy
      and theoretical simulation provides new insights. The complex chi((2)) spectra of
      isotopically diluted water surfaces obtained by heterodyne-detected sum frequency
      generation spectroscopy and molecular dynamics simulation show excellent
      agreement, assuring the validity of the microscopic picture given in the
      simulation. The present study indicates that there is no ice-like structure at
      the surface--in other words, there is no increase of tetrahedrally coordinated
      structure compared to the bulk--but that there are water pairs interacting with a
      strong hydrogen bond at the outermost surface. Intuitively, this can be
      considered a consequence of the lack of a hydrogen bond toward the upper gas
      phase, enhancing the lateral interaction at the boundary. This study also
      confirms that the major source of the isotope effect on the water chi((2))
      spectra is the intramolecular anharmonic coupling, i.e., Fermi resonance.

PMID- 21899355
TI  - Dynamics of water at the interface in reverse micelles: measurements of spectral
      diffusion with two-dimensional infrared vibrational echoes.
AB  - Water dynamics inside of reverse micelles made from the surfactant Aerosol-OT
      (AOT) were investigated by observing spectral diffusion, orientational
      relaxation, and population relaxation using two-dimensional infrared (2D IR)
      vibrational echo spectroscopy and pump-probe experiments. The water pool sizes of
      the reverse micelles studied ranged in size from 5.8 to 1.7 nm in diameter. It is
      found that spectral diffusion, characterized by the frequency-frequency
      correlation function (FFCF), significantly changes as the water pool size
      decreases. For the larger reverse micelles (diameter 4.6 nm and larger), the 2D
      IR signal is composed of two spectral components: a signal from bulk-like core
      water, and a signal from water at the headgroup interface. Each of these signals
      (core water and interfacial water) is associated with a distinct FFCF. The FFCF
      of the interfacial water layer can be obtained using a modified center line slope
      (CLS) method that has been recently developed. The interfacial FFCFs for large
      reverse micelles have a single exponential decay (~1.6 ps) to an offset plus a
      fast homogeneous component and are nearly identical for all large sizes. The
      observed ~1.6 ps interfacial decay component is approximately the same as that
      found for bulk water and may reflect hydrogen bond rearrangement of bulk-like
      water molecules hydrogen bonded to the interfacial water molecules. The long time
      offset arises from dynamics that are too slow to be measured on the accessible
      experimental time scale. The influence of the chemical nature of the interface on
      spectral diffusion was explored by comparing data for water inside reverse
      micelles (5.8 nm water pool diameter) made from the surfactants AOT and Igepal CO
      520. AOT has charged, sulfonate head groups, while Igepal CO-520 has neutral,
      hydroxyl head groups. It is found that spectral diffusion on the observable time
      scales is not overly sensitive to the chemical makeup of the interface. An
      intermediate-sized AOT reverse micelle (water pool diameter of 3.3 nm) is
      analyzed as a large reverse micelle because it has distinct core and interface
      regions, but its core region is more constrained than bulk water. The interfacial
      FFCF for this intermediate-sized reverse micelle is somewhat slower than those
      found for the larger reverse micelles. The water nanopools in the smaller reverse
      micelles cannot be separated into core and interface regions. In the small
      reverse micelles, the FFCFs are biexponential decays to an offset plus a fast
      homogeneous component. Each small reverse micelle exhibits an ~1 ps decay time,
      which may arise from local hydrogen bond fluctuations and a slower, ~6-10 ps
      decay, which is possibly due to slow hydrogen bond rearrangement of
      noninterfacial water molecules or topography fluctuations at the interface.

PMID- 21899356
TI  - Localization of multiple DNA sequences on nanopatterns.
AB  - DNA oligonucleotides of different sequences were patterned at the nanoscale.
      Areas of positive charge were generated by exposure of insulating substrates,
      spin-on hydrogen silsesquioxane or vapor-deposited SiO(2) on Si, with ionizing
      radiation sources used in electron beam and extreme ultraviolet lithography. Au
      nanoparticles (NPs) with a diameter of 15 nm, carrying covalently bound
      negatively charged single-stranded DNA oligonucleotides, were site specifically
      immobilized directly on the exposed regions and presented oligonucleotides for
      subsequent hybridization. Repeated exposure and deposition of NPs allowed for
      patterning multiple DNA sequences. Patterns with dimensions as small as 15 nm
      were fabricated using electron beam lithography. The use of DNA-functionalized
      NPs rather than just DNA facilitates metrology in scanning electron microscopy
      and improves the hybridization efficiency of the oligonucleotides on the surface.

PMID- 21899357
TI  - High-yield production and transfer of graphene flakes obtained by anodic bonding.
AB  - We report large-yield production of graphene flakes on glass by anodic bonding.
      Under optimum conditions, we counted several tens of flakes with lateral size
      around 20-30 MUm and a few tens of flakes with larger size. About 60-70% of the
      flakes have a negligible D peak. We show that it is possible to easily transfer
      the flakes by the wedging technique. The transfer on silicon does not damage
      graphene and lowers the doping. The charge mobility of the transferred flakes on
      silicon is on the order of 6000 cm(2)/V s (at a carrier concentration of 10(12)
      cm(-2)), which is typical for devices prepared on this substrate with exfoliated
      graphene.

PMID- 21899358
TI  - High selectivity for primary C-H bond cleavage of propane sigma-complexes on the
      PdO(101) surface.
AB  - We investigated regioselectivity in the initial C-H bond activation of propane
      sigma-complexes on the PdO(101) surface using temperature programmed reaction
      spectroscopy (TPRS) experiments. We observe a significant kinetic isotope effect
      (KIE) in the initial C-H(D) bond cleavage of propane on PdO(101) such that the
      dissociation yield of C(3)H(8) is 2.7 times higher than that of C(3)D(8) at
      temperatures between 150 and 200 K. Measurements of the reactivity of
      (CH(3))(2)CD(2) and (CD(3))(2)CH(2) show that deuteration of the methyl groups is
      primarily responsible for the lower reactivity of C(3)D(8) relative to C(3)H(8),
      and thus that 1 degrees  C-H bond cleavage is the preferred pathway for propane
      activation on PdO(101). By analyzing the rate data within the context of a
      kinetic model for precursor-mediated dissociation, we estimate that 90% of the
      propane sigma-complexes which dissociate on PdO(101) during TPRS do so by 1
      degrees  C-H bond cleavage.

PMID- 21899359
TI  - Protein-binding affinity of  leucaena  condensed tannins of differing molecular
      weights.
AB  - Depending on their source, concentration, chemical structure, and molecular
      weight, condensed tannins (CTs) form insoluble complexes with protein, which
      could lead to ruminal bypass protein, benefiting animal production. In this
      study, CTs from  Leuceana leucocephala  hybrid were fractionated into five
      fractions by a size exclusion chromatography procedure. The molecular weights of
      the CT fractions were determined using Q-TOF LC-MS, and the protein-binding
      affinities of the respective CT fractions were determined using a protein
      precipitation assay with bovine serum albumin (BSA) as the standard protein. The
      calculated number-average molecular weights (M(n)) were 1348.6, 857.1, 730.1,
      726.0, and 497.1, and b values (the b value represents the CT quantity that is
      needed to bind half of the maximum precipitable BSA) of the different molecular
      weight fractions were 0.381, 0.510, 0.580, 0.636, and 0.780 for fractions 1, 2,
      3, 4, and 5, respectively. The results indicated that, in general, CTs of higher
      molecular weight fractions have stronger protein-binding affinity than those of
      lower molecular weights. However, the number of hydroxyl units within the
      structure of CT polymers also affects the protein-binding affinity.

PMID- 21899360
TI  - Cell patterning using a template of microstructured organosilane layer fabricated
      by vacuum ultraviolet light lithography.
AB  - Micropatterning techniques have become increasingly important in cellular
      biology. Cell patterning is achieved by various methods. Photolithography is one
      of the most popular methods, and several light sources (e.g., excimer lasers and
      mercury lamps) are used for that purpose. Vacuum ultraviolet (VUV) light that can
      be produced by an excimer lamp is advantageous for fabricating material patterns,
      since it can decompose organic materials directly and efficiently without
      photoresist or photosensitive materials. Despite the advantages, applications of
      VUV light to pattern biological materials are few. We have investigated cell
      patterning by using a template of a microstructured organosilane layer fabricated
      by VUV lithography. We first made a template of a microstructured organosilane
      layer by VUV lithography. Cell adhesive materials (poly(d-lysine) and
      polyethyleneimine) were chemically immobilized on the organosilane template,
      producing a cell adhesive material pattern. Primary rat cardiac and neuronal
      cells were successfully patterned by culturing them on the pattern substrate.
      Long-term culturing was attained for up to two weeks for cardiac cells and two
      months for cortex cells. We have discussed the reproducibility of cell patterning
      and made suggestions to improve it.

PMID- 21899361
TI  - On-surface covalent linking of organic building blocks on a bulk insulator.
AB  - On-surface synthesis in ultrahigh vacuum provides a promising strategy for
      creating thermally and chemically stable molecular structures at surfaces. The
      two-dimensional confinement of the educts, the possibility of working at higher
      (or lower) temperatures in the absence of solvent, and the templating effect of
      the surface bear the potential of preparing compounds that cannot be obtained in
      solution. Moreover, covalently linked conjugated molecules allow for efficient
      electron transport and are, thus, particularly interesting for future molecular
      electronics applications. When having these applications in mind, electrically
      insulating substrates are mandatory to provide sufficient decoupling of the
      molecular structure from the substrate surface. So far, however, on-surface
      synthesis has been achieved only on metallic substrates. Here we demonstrate the
      covalent linking of organic molecules on a bulk insulator, namely, calcite. We
      deliberately employ the strong electrostatic interaction between the carboxylate
      groups of halide-substituted benzoic acids and the surface calcium cations to
      prevent molecular desorption and to reach homolytic cleavage temperatures. This
      allows for the formation of aryl radicals and intermolecular coupling. By varying
      the number and position of the halide substitution, we rationally design the
      resulting structures, revealing straight lines, zigzag structures, and dimers,
      thus providing clear evidence for the covalent linking. Our results constitute an
      important step toward exploiting on-surface synthesis for molecular electronics
      and optics applications, which require electrically insulating rather than
      metallic supporting substrates.

PMID- 21899362
TI  - Light-weight flexible carbon nanotube based organic composites with large
      thermoelectric power factors.
AB  - Typical organic materials have low thermal conductivities that are best suited to
      thermoelectrics, but their poor electrical properties with strong adverse
      correlations have prevented them from being feasible candidates. Our composites,
      containing single-wall carbon nanotubes, poly(3,4
      ethylenedioxythiophene):poly(styrenesulfonate) and/or polyvinyl acetate, show
      thermopowers weakly correlated with electrical conductivities, resulting in large
      thermoelectric power factors in the in-plane direction of the composites, ~160
      MUW/m.K(2) at room temperature, which are orders of magnitude larger than those
      of typical polymer composites. Furthermore, their high electrical conductivities,
      ~10(5) S/m at room temperature, make our composites very promising for various
      electronic applications. The optimum nanotube concentrations for better power
      factors were identified to be 60 wt % with 40 wt % polymers. It was noticed that
      high nanotube concentrations above 60 wt % decreased the electrical conductivity
      of the composites due to less effective nanotube dispersions. The thermal
      conductivities of our 60 wt % nanotube composites in the out-of-plane direction
      were measured to be 0.2-0.4 W/m.K at room temperature. The in-plane thermal
      conductivity and thermal contact conductance between nanotubes were also
      theoretically estimated.

PMID- 21899363
TI  - Self-assembly of collagen-mimetic peptide amphiphiles into biofunctional
      nanofiber.
AB  - Molecular assembly of protein and peptide is highly specific and frequently
      occurs in biological systems. Collagen, which is the most abundant component in
      extracellular matrix, can assemble into fiber and play an essential role in cell
      adhesion and growth. Since native collagen is difficult to modify and can
      engender pathogenic and immunological side effects, its application on tissue
      regeneration is limited. The preparation of collagen-mimetic materials, hence, is
      gaining interest in the field of tissue regeneration. Collagen peptides have been
      synthesized to mimic some properties of collagen, such as its triple helix.
      However, few studies have been done to prepare artificial collagen fiber to mimic
      its high-level structure and biofunctions. In this work, a novel collagen-mimetic
      peptide amphiphile (CPA) was prepared by conjugating a single hydrophobic tail
      with a collagen-mimetic peptide, supplemented with bioactive glycine
      phenylalanine-hydroxyproline-glycine-glutamate-arginine (GFOGER). The physical
      studies indicated that the CPA had a collagen-mimetic triple-helical conformation
      and was able to self-assemble into nanofiber. In addition, the CPA conjugated
      with the integrin-specific GFOGER sequence was shown to promote collagen-mimetic
      cell adhesion and development. The self-assembled peptide nanofiber was shown to
      have the ability to structurally and biologically mimic native collagen fiber. We
      anticipate that this artificial collagen fiber holds great potential as collagen
      mimetic materials for tissue regeneration applications.

PMID- 21899364
TI  - Ent-2'-epi-Orobanchol and its acetate, as germination stimulants for Striga
      gesnerioides seeds isolated from cowpea and red clover.
AB  - Striga gesnerioides is a root parasitic weed of economic significance to cowpea
      (Vigna unguiculata) crops in Western Africa. Seeds of the parasite germinate in
      response to cowpea root exudates. Germination stimulants for the seeds were
      isolated from the hydroponic culture filtrate of cowpea, and their structures
      were unambiguously determined as (-)-(3aR,4R,8bR,2'R)-ent-2'-epi-orobanchol and
      (+)-(3aR,4R,8bR,2'R)-ent-2'-epi-orobanchyl acetate, on the basis of mass, CD, and
      (1)H NMR spectra; optical rotatory power; and chromatographic behavior on HPLC.
      The alcohol was first isolated and identified from the cowpea root exudates, and
      the acetate may be the same compound that had been previously isolated from the
      exudates and designated as alectrol. Identity of the stimulants produced by
      cowpea to those produced by red clover (Trifolium pratense) was confirmed.

PMID- 21899365
TI  - Crotalaria medicaginea associated with horse deaths in northern Australia: new
      pyrrolizidine alkaloids.
AB  - Crotalaria medicaginea  has been implicated in horse poisoning in grazing regions
      of central-west Queensland, which resulted in the deaths of more than 35 horses
      from hepatotoxicosis in 2010. Liver pathology was suggestive of pyrrolizidine
      alkaloidosis, and we report here the isolation of two previously uncharacterized
      pyrrolizidine alkaloids from C. medicaginea plant specimens collected from
      pastures where the horses died. The first alkaloid was shown by mass spectometric
      and NMR analyses to be 1beta,2beta-epoxy-7beta-hydroxy-1alpha-methoxymethyl
      8alpha-pyrrolizidine, which, like other alkaloids previously isolated from C.
      medicaginea, lacks the requisite functionality for hepatotoxcity. The second
      alkaloid isolated in this investigation was a new macrocyclic diester of
      otonecine, which we have named cromedine. The (1)H and (13)C NMR spectra of
      cromedine were fully assigned by 2D NMR techniques and allowed the constitution
      of the macrocyclic diester to be assigned unambiguously. C. medicaginea specimens
      implicated in this investigation do not belong to any of the three recognized
      Australian varieties (C. medicaginea var. neglecta, C. medicaginea var.
      medicaginea, and C. medicaginea var. linearis) and appear to be a local variant
      or form, referred to here as C. medicaginea (chemotype cromedine).

PMID- 21899366
TI  - Metabolic dependence of green tea on plucking positions revisited: a metabolomic
      study.
AB  - The dependence of global green tea metabolome on plucking positions was
      investigated through (1)H nuclear magnetic resonance (NMR) analysis coupled with
      multivariate statistical data set. Pattern recognition methods, such as principal
      component analysis (PCA) and orthogonal projection on latent structure
      discriminant analysis (OPLS-DA), were employed for a finding metabolic
      discrimination among fresh green tea leaves plucked at different positions from
      young to old leaves. In addition to clear metabolic discrimination among green
      tea leaves, elevations in theanine, caffeine, and gallic acid levels but
      reductions in catechins, such as epicatechin (EC), epigallocatechin (EGC),
      epicatechin-3-gallate (ECG), and epigallocatechin-3-gallate (EGCG), glucose, and
      sucrose levels were observed, as the green tea plant grows up. On the other hand,
      the younger the green tea leaf is, the more theanine, caffeine, and gallic acid
      but the lesser catechins accumlated in the green tea leaf, revealing a reverse
      assocation between theanine and catechins levels due to incorporaton of theanine
      into catechins with growing up green tea plant. Moreover, as compared to the tea
      leaf, the observation of marked high levels of theanine and low levels of
      catechins in green tea stems exhibited a distinct tea plant metabolism between
      the tea leaf and the stem. This metabolomic approach highlights taking insight to
      global metabolic dependence of green tea leaf on plucking position, thereby
      providing distinct information on green tea production with specific tea quality.

PMID- 21899367
TI  - Molecular insight into conformational transition of amyloid beta-peptide 42
      inhibited by (-)-epigallocatechin-3-gallate probed by molecular simulations.
AB  - Considerable experimental evidence indicates that (-)-epigallocatechin-3-gallate
      (EGCG) inhibits the fibrillogenesis of Abeta(42) and alleviates its associated
      cytotoxicity. However, the molecular mechanism of the inhibition effect of EGCG
      on the conformational transition of Abeta(42) remains unclear due to the
      limitations of current experimental techniques. In this work, molecular dynamics
      simulations and molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA)
      analysis were coupled to better understand the issue. It was found that the
      direct interactions between EGCG and the peptide are the origin of its inhibition
      effects. Specifically, EGCG molecules expel water from the surface of the
      Abeta(42), cluster with each other, and interact directly with the peptide. The
      results of free energy decomposition calculated by MM-PBSA indicate that the
      nonpolar term contributes more than 71% to the binding free energy of the EGCG
      Abeta(42) complex, while polar interactions (i.e., hydrogen bonding) play a minor
      role. It was identified that there are 12 important residues of Abeta(42) that
      strongly interact with EGCG (Phe4, Arg5, Phe19, Phe20, Glu22, Lys28, Gly29, Leu34
      Gly37, and Ile41), while nonpolar interactions are mainly provided by the side
      chains of some hydrophobic residues (Phe, Met and Ile) and the main chains of
      some nonhydrophobic residues (Lys28 and Gly29). On the contrary, polar
      interactions are mainly formed by the main chain of Abeta(42), of which the main
      chains of Gly29 and Gly37 contribute greatly. The work has thus elucidated the
      molecular mechanism of the inhibition effect of EGCG on the conformational
      transition of Abeta(42), and the findings are considered critical for exploring
      more effective agents for the inhibition of Abeta(42) fibrillogenesis.

PMID- 21899368
TI  - Copper-free Sonogashira cross-coupling for functionalization of alkyne-encoded
      proteins in aqueous medium and in bacterial cells.
AB  - Bioorthogonal reactions suitable for functionalization of genetically or
      metabolically encoded alkynes, for example, copper-catalyzed azide-alkyne
      cycloaddition reaction ("click chemistry"), have provided chemical tools to study
      biomolecular dynamics and function in living systems. Despite its prominence in
      organic synthesis, copper-free Sonogashira cross-coupling reaction suitable for
      biological applications has not been reported. In this work, we report the
      discovery of a robust aminopyrimidine-palladium(II) complex for copper-free
      Sonogashira cross-coupling that enables selective functionalization of a
      homopropargylglycine (HPG)-encoded ubiquitin protein in aqueous medium. A wide
      range of aromatic groups including fluorophores and fluorinated aromatic
      compounds can be readily introduced into the HPG-containing ubiquitin under mild
      conditions with good to excellent yields. The suitability of this reaction for
      functionalization of HPG-encoded ubiquitin in Escherichia coli was also
      demonstrated. The high efficiency of this new catalytic system should greatly
      enhance the utility of Sonogashira cross-coupling in bioorthogonal chemistry.

PMID- 21899369
TI  - Investigation of the interface in silica-encapsulated liposomes by combining
      solid state NMR and first principles calculations.
AB  - In the context of nanomedicine, liposils (liposomes and silica) have a strong
      potential for drug storage and release schemes: such materials combine the
      intrinsic properties of liposome (encapsulation) and silica (increased rigidity,
      protective coating, pH degradability). In this work, an original approach
      combining solid state NMR, molecular dynamics, first principles geometry
      optimization, and NMR parameters calculation allows the building of a precise
      representation of the organic/inorganic interface in liposils. {(1)H-(29)Si}(1)H
      and {(1)H-(31)P}(1)H Double Cross-Polarization (CP) MAS NMR experiments were
      implemented in order to explore the proton chemical environments around the
      silica and the phospholipids, respectively. Using VASP (Vienna Ab Initio
      Simulation Package), DFT calculations including molecular dynamics, and geometry
      optimization lead to the determination of energetically favorable configurations
      of a DPPC (dipalmitoylphosphatidylcholine) headgroup adsorbed onto a hydroxylated
      silica surface that corresponds to a realistic model of an amorphous silica slab.
      These data combined with first principles NMR parameters calculations by GIPAW
      (Gauge Included Projected Augmented Wave) show that the phosphate moieties are
      not directly interacting with silanols. The stabilization of the interface is
      achieved through the presence of water molecules located in-between the head
      groups of the phospholipids and the silica surface forming an interfacial H
      bonded water layer. A detailed study of the (31)P chemical shift anisotropy (CSA)
      parameters allows us to interpret the local dynamics of DPPC in liposils.
      Finally, the VASP/solid state NMR/GIPAW combined approach can be extended to a
      large variety of organic-inorganic hybrid interfaces.

PMID- 21899370
TI  - SAR and LC/MS studies of beta-lactamic inhibitors of human fatty acid amide
      hydrolase (hFAAH): evidence of a nonhydrolytic process.
AB  - The endocannabinoid hydrolyzing enzyme FAAH uses a nonclassical catalytic triad
      (namely, Ser-Ser-Lys instead of Ser-Asp-His) to cleave its endogenous substrates.
      Because inhibiting FAAH has a clear therapeutic potential, we previously
      developed beta-lactam-type inhibitors of hFAAH. Here, we report the synthesis of
      five novel derivatives (5-9) of our lead compound 1-(pent-4-enoyl)-3(S)-[1(R)-(4
      phenylbutanoyloxy)-ethyl]-azetidin-2-one (4, IC(50) = 5 nM) obtained via the
      systematic replacement of one to three carbonyls by methylene groups. The SAR
      results showed that the imide, but not the lactam, function is essential to the
      inhibition of hFAAH. We also performed LC/MS analysis following incubation of our
      inhibitors with hFAAH or mouse liver. We demonstrated that hFAAH interacts with
      these beta-lactam-type inhibitors but, unexpectedly, does not open the beta
      lactam moiety. This mechanism seems to be unique to FAAH because the beta-lactam
      function of the inhibitors is hydrolyzed when they are incubated in the presence
      of the serine hydrolases expressed in the mouse liver. Finally, we confirmed
      these results by showing that a highly selective FAAH inhibitor (PF-750) does not
      prevent this hydrolysis by liver homogenates.

PMID- 21899372
TI  - Synthesis of a base-stabilized silanone-coordinated complex by oxygenation of a
      (silyl)(silylene)tungsten complex.
AB  - Base-stabilized silanone complex Cp*(OC)(2)W(SiMe(3)){O?SiMes(2)(DMAP)} (2) was
      synthesized by the reaction of (silyl)(silylene)tungsten complex
      Cp*(OC)(2)W(SiMe(3))(?SiMes(2)) (1) with 1 equiv of pyridine-N-oxide (PNO) in the
      presence of 4-(dimethylamino)pyridine (DMAP). Further oxygenation of 2 with 3
      equiv of PNO at 80  degrees C resulted in the formation of a W-O-Si-O-Si
      framework to give disiloxanoxy complex Cp*(O)(2)W{OSiMes(2)(OSiMe(3))} (3).
      Complex 3 was also obtained by the direct reaction of complex 1 with 4 equiv of
      PNO at 80  degrees C.

PMID- 21899373
TI  - New generation of dialkylsilylenes with stabilities comparable to
      diaminosilylenes: a theoretical study.
AB  - A new family of dialkylsilylenes is introduced which enjoys the stabilizing
      effect of alpha-cyclopropyl substituents. The singlet and triplet states of
      acyclic and saturated/unsaturated cyclic dicyclopropylsilylenes are fully
      optimized using MP2/6-31G(d) and B3LYP/6-31+G(d) levels. Their higher DeltaE(S-T)
      values compared to the corresponding analogues which possess isopropyl groups
      instead of cyclopropyl represents the stabilizing interaction of the occupied
      Walsh orbital of the cyclopropyls with the vacant p-orbital of the silylene
      center. Appropriate isodesmic reactions clearly show that the stabilizing effect
      of this interaction on the singlet state is much more considerable than the
      corresponding triplet state. Cyclopropyls can serve as good sites for bulky
      substitution and, hence, provide steric protection for silylene.

PMID- 21899371
TI  - Simple, direct conjugation of bacterial O-SP-core antigens to proteins:
      development of cholera conjugate vaccines.
AB  - Bacterial O-SP-core antigens can be conjugated to proteins in the same, simple
      way as synthetic, linker-equipped carbohydrates by applying squaric acid
      chemistry. Introduction of spacers (linkers) to either O-SP-core antigens or
      protein carriers, which is involved in commonly applied protocols, is not
      required. The newly developed method described here consists of preparation of a
      squaric acid monoester derivative of O-SP-core antigen, utilizing the amino group
      inherent in the core, and reaction of the monoester with the carrier protein. The
      intermediate monoester can be easily purified; its conjugation can be monitored
      by SELDI-TOF mass spectrometry and, thus, readily controlled, since the
      conjugation can be terminated when the desired carbohydrate-protein ratio is
      reached. Here, we describe production of conjugates containing the O-SP-core
      antigen of Vibrio cholerae O1, the major cause of cholera, a severe dehydrating
      diarrheal disease of humans. The resultant products are recognized by
      convalescent phase sera from patients recovering from cholera in Bangladesh, and
      anti-O-SP-core-protein responses correlate with plasma antilipopolysaccharide and
      vibriocidal responses, which are the primary markers of protection from cholera.
      The results suggest that such conjugates have potential as vaccines for cholera
      and other bacterial diseases.

PMID- 21899374
TI  - Computational insight into the electronic structure and absorption spectra of
      lithium complexes of N-confused tetraphenylporphyrin.
AB  - The present work is a theoretical investigation on lithium complexes of N
      confused tetraphenylporphyrins (aka inverted) employing density functional theory
      (DFT) and time-dependent DFT, using the B3LYP, CAM-B3LYP, and M06-2X functionals
      in conjunction with the 6-31G(d,p) basis set. The purpose of the present study is
      to calculate the electronic structure and the bonding of the complexes to explain
      the unusual coordination environment in which Li is found experimentally and how
      the Li binding affects the Q and the Soret bands. The calculations show that,
      unlike a typical tetrahedral Li(+) cation, this Li forms a typical bond with one
      N and interacts with the remaining two N atoms, and it is located in the right
      place to form an agostic-like interaction with the internal C atom. The reaction
      energy, the enthalpy for the formation of the lithium complexes of N-confused
      porphyrins, and the effect of solvation are also calculated. The insertion of Li
      into N-confused porphyrin, in the presence of tetrahydrofuran, is exothermic with
      a reaction energy calculated to be as high as -72.4 kcal/mol using the lithium
      bis(trimethylsilyl)amide reagent. Finally, there is agreement in the general
      shape among the vis-UV spectra determined with different functionals and the
      experimentally available ones. The calculated geometries are in agreement with
      crystallographic data, where available.

PMID- 21899375
TI  - Determinants of apparent rural-urban differentials in measles vaccination uptake
      in Indonesia.
AB  - INTRODUCTION: Regional differences in vaccination uptake are common in both
      developed and developing countries, and are often linked to the availability of
      healthcare services and socioeconomic factors. In 2007, 0.9 million eligible
      Indonesian children missed measles vaccination, and 19 456 cases of measles were
      documented among Indonesian children. The authors investigated rural-urban
      differentials in measles vaccination coverage among young Indonesian children,
      and sought to identify key factors influencing the probability of a child
      receiving the first dose of measles vaccination in Indonesia. METHODS: Data used
      in the analyses were sourced from the nationally representative Indonesia
      Demographic and Health Survey 2007. The influence of location of residence,
      household wealth, maternal and paternal education, total children ever born and
      use of skilled birth attendants on measles vaccination coverage was investigated
      using bivariate analysis and chi-square tests. The independent effects of these
      variables were established using binomial logistic regression analysis. RESULTS:
      Indonesia's 2007 first-dose measles national vaccination coverage was, at 72.8%,
      lower than the 2008 global first-dose measles vaccination average coverage of
      82%. Bivariate analysis revealed that the first-dose measles vaccination coverage
      in rural areas of Indonesia was 68.5%, compared with 80.1% in urban regions (p <
      0.001). The apparent significance of rural residence in impairing vaccination
      coverage was marginal after controlling for the sex of the child, maternal age,
      maternal and paternal education, wealth, and access to skilled health workers.
      CONCLUSION: Apart from sustainable initiatives to increase measles vaccination
      coverage globally, it is important to close the rural-urban gap in Indonesia's
      measles vaccination uptake. Addressing critical determinants of inferior measles
      vaccination coverage in Indonesia's rural regions will facilitate major
      improvements in Indonesia's child health trends. This article suggests
      initiatives for addressing three of such determinants in Indonesia's rural areas:
      poverty, parental education and access to skilled health workers.

PMID- 21899376
TI  - Changes in CT cerebral blood flow and volume associated with rapid maxillary
      expansion in a rabbit model.
AB  - OBJECTIVE: To evaluate hemodynamic changes of the brain under the high forces of
      a rapid maxillary expansion (RME) appliance in a rabbit model. MATERIALS AND
      METHODS: Twenty-four male New Zealand white rabbits were selected (12 weeks old,
      mean weight 3.01 +/- 0.22 kg). A modified acrylic resin bonded RME appliance was
      used for expansion. A series of perfusion computed tomography examinations was
      performed before expansion (T0), on the fifth day of expansion (T1), at the end
      of the expansion process (T2), and after 10 days of retention (T3). Cerebral
      blood flow, cerebral blood volume, and mean transit time maps were recorded and
      parametrics evaluated. Statistical analyses were performed with analysis of
      variance with post hoc tests. RESULTS: Mean cerebral blood flow showed an
      increase from T0 to T2 and then a decrease from T2 to T3, but the change was not
      statistically significant. Mean cerebral blood volume and mean transit time
      increased significantly from T0 to T2, and all perfusion parameters increased
      from T0 to T3. CONCLUSIONS: RME is a safe orthopedic method despite the high
      expansion force. Perfusion computed tomography is effective for evaluating the
      hemodynamic changes of the brain caused by some orthopedic therapies. The
      increase in both cerebral blood volume and cerebral blood flow may help to
      explain why RME could alleviate the symptoms of enuretic children.

PMID- 21899377
TI  - Skeletal maturation evaluation using mandibular second molar calcification
      stages.
AB  - OBJECTIVE: To investigate (1) the relationships between the stages of mandibular
      second molar calcification and skeletal maturity; and (2) whether second molar
      calcification stages can be used as a reliable diagnostic tool to determine
      skeletal maturity. MATERIALS AND METHODS: Samples were derived from panoramic
      radiographs and lateral cephalograms of 300 subjects (137 males and 163 females)
      with ages ranging from 9 to 18 years, and estimates of dental maturity (Demirjian
      Index [DI]) and skeletal maturity (cervical vertebrae maturation indicators
      [CVMI]) were made. RESULTS: A highly significant association (C*  =  0.854 for
      males and 0.866 for females) was found between DI and CVMI. DI stage E
      corresponded to stage 2 of CVMI (pre-peak of pubertal growth spurt) and DI stages
      F and G corresponded to stages 3 and 4 of CVMI (peak of pubertal growth spurt).
      DI stage H was associated with stages 5 and 6 of CVMI (end of pubertal growth
      spurt). CONCLUSION: A highly significant association exists between DI and CVMI.
      Mandibular second molar DI stages are reliable indicators of skeletal maturity.

PMID- 21899378
TI  - Risk factors for periodontal changes in adult patients with banded second molars
      during orthodontic treatment.
AB  - OBJECTIVE: To identify the risk factors for periodontal changes in adult patients
      during orthodontic treatment by evaluating the periodontal status of banded
      second molars using the gingival index (GI). MATERIAL AND METHODS: The sample
      consisted of 100 adult patients divided into two groups: the Orthodontics group,
      undergoing corrective treatment with fixed appliances and bands cemented to the
      four second molars, and the Control group, with no prior history of orthodontic
      treatment, age and sex matched. Group GI values were compared using the Wilcoxon
      test. Additionally, a multivariate logistic regression was performed to study the
      risk factors for increases in the GI. RESULTS: Individuals in the Orthodontics
      group showed a significantly higher GI than those in the Control group. Logistic
      regression revealed that among the risk factors found to increase GI, the
      following proved significant (in order of importance): plaque index, subgingival
      encroachment of the cervical margins of bands, probing depth, and length of
      orthodontic treatment. CONCLUSIONS: Banded second molars of adult patients during
      orthodontic treatment showed more clinical signs of gingival inflammation than
      those of untreated individuals. Moreover, major risk factors identified included
      the presence of plaque and the presence of subgingival band margins.

PMID- 21899379
TI  - Maxillary surgical seeding of a clival chordoma.
AB  - Seeding on surgical pathway is a rare form of clival chordoma treatment failure.
      We report the case of a 42-year-old male with a clival chondroid chordoma removed
      by a sublabial transsphenoidal approach followed by proton beam radiotherapy, who
      developed a maxillary bone recurrence 3 years after surgery.

PMID- 21899380
TI  - Estimation of cerebrospinal fluid compensation parameters in hydrocephalus using
      short-lasting constant rate lumbar infusion tests.
AB  - OBJECTIVES: The lumbar infusion test is an invasive technique for quantifying
      cerebrospinal dynamics in patients with hydrocephalus. However, some patients
      have difficulty tolerating the duration of this procedure. Therefore, we
      investigated the limits of shortening the test by examining the reliability of
      cerebrospinal fluid (CSF) compensatory parameters as a function of time. METHODS:
      We analysed recordings of the intracranial cerebral pressure (ICP) response to a
      constant, high-rate infusion of saline (2 ml/min) lasting 5.7-20 (12 +/- 10) min
      in 30 patients with a preliminary diagnosis of hydrocephalus (13 men, aged 37-81
      [65 +/- 10] years). We performed computerised identification of CSF outflow
      resistance (R(out)), intracranial compliance parameters: elastance index (E) and
      reference pressure (P(0)), based on the truncated ICP response (20-100% of the
      available test length), estimating either all three parameters (3p method) or
      only R(out) and E (2p method) assuming P(0) as the regression between the ICP and
      its amplitude. RESULTS: Following considerable variation during the initial rise
      of ICP, R(out) typically converged within +/- 10% of their final values within 10
      15 min. Final R(out) values were 4-40 (12 +/- 6) mmHg/ml/min, and were method
      independent (R(2) = 0.97). Compliance parameters (E, typically 0.1-0.5/ml; P(0): 
      10 to + 20 mmHg) agreed poorly between methods (R(2) = 0.3-0.7) and varied
      considerably within the observed infusion periods. CONCLUSION: The lumbar
      infusion test may be shortened to 10-15 min using a rapid infusion rate of 2
      ml/min that fulfils the primary objective of obtaining reliable estimates of
      R(out). This may benefit patients who do not tolerate the full procedure.

PMID- 21899381
TI  - Cervical radiculopathy: discrepancy or concordance between electromyography and
      magnetic resonance imaging?
AB  - In the screening of patients with cervical radiculopathy, a relatively common
      finding is the discrepancy between normal needle electromyography (EMG) and
      abnormal MRI, or vice versa. We carried out a retrospective study to assess the
      relationship between needle EMG and MRI findings in the preoperative evaluation
      of patients with cervical radiculopathy. The records of 147 patients were
      reviewed; 58 patients (M = 32, F = 26; age 53 +/- 9) were included in the study.
      Needle EMG examination was abnormal in 28 patients. MRI abnormalities were found
      in all 58 patients, showing degenerative changes not affecting the nerve root in
      15 and foraminal stenosis affecting the nerve root in 43; in the latter, needle
      EMG was abnormal in 28 patients and normal in the remainder. Concordance between
      EMG and MRI level of abnormality was found in 71% of patients with non-dermatomal
      symptom distribution. Concordance between clinical level, EMG and MRI abnormality
      was found in 50% of patients with C5, in 70% with C6 and in 67% with C7 symptom
      distribution. When EMG and MRI level of abnormality was discordant, the EMG
      abnormalities corresponded to the clinical level of symptom distribution. The
      results of our retrospective study reveal that in the majority of cases of
      cervical radiculopathy, EMG and MRI level of abnormalities are concordant. When
      there is discordance between EMG and MRI findings, the EMG helps in the guidance
      of patient selection for surgical intervention because it provides evidence of
      nerve root lesion and offers a dynamic tool in the follow-up evaluation.

PMID- 21899382
TI  - Good airway reflexes and normal sensorium do not assure safe tracheal extubation
      in patients with cerebral hemispheric pathology.
AB  - Following brain injury, return of consciousness and cough reflex are presumed to
      be associated with safe airway. We describe two patients who had a normal cough
      reflex, but impaired swallowing, which led to prolonged hospital stay. This
      report highlights the dissociation between the cough reflex and swallowing
      function in such patients.

PMID- 21899383
TI  - Incidental aneurysms in temporal lobe epilepsy surgery: report of three cases and
      a review of the literature.
AB  - OBJECTIVE AND IMPORTANCE: In rare instances, patients who are undergoing
      evaluation for temporal lobe epilepsy surgery will also be found to have an
      incidental aneurysm adjacent to the temporal lobe. Although busy epilepsy centers
      will eventually come across cases like this, to our knowledge there are currently
      no publications regarding such cases or the complex management decisions that
      follow in caring for these patients. Factors affecting decision making in these
      cases are discussed in detail. CLINICAL PRESENTATION: Three cases where an
      incidental aneurysm was discovered during the evaluation and treatment of
      temporal lobe epilepsy are discussed. Two cases of middle cerebral artery (MCA)
      aneurysm, one ipsilateral to the planned temporal lobectomy and one contralateral
      aneurysm unsuitable for coiling, were discovered preoperatively. In one case, an
      incidental posterior cerebral artery (PCA) aneurysm was noted during an
      amygdalohippocampectomy. Intervention. In the ipsilateral MCA aneurysm case, the
      aneurysm was clipped during the temporal lobectomy. In the case of a
      contralateral MCA aneurysm, the aneurysm was electively clipped prior to the
      temporal lobectomy. In the PCA aneurysm case, the aneurysm was clipped at the
      time of discovery during surgery. CONCLUSION: Incidentally noted unruptured
      aneurysms in patients undergoing evaluation and treatment of medically
      intractable epilepsy add a level of complexity to medical decision making in
      these cases. Factors affecting treatment decisions include the size and location
      of the aneurysm, risks of aneurysm treatment, patient age, severity of the
      epilepsy condition and patient wishes after discussion of treatment options.

PMID- 21899385
TI  - High-throughput screening and analysis of genes of Xanthomonas citri subsp. citri
      involved in citrus canker symptom development.
AB  - Citrus canker is caused by Xanthomonas citri subsp. citri and is one of the most
      devastating diseases on citrus plants. To investigate the virulence mechanism of
      this pathogen, a mutant library of strain 306 containing approximately 22,000
      mutants was screened for virulence-deficient mutants in grapefruit (Citrus
      paradise). Eighty-two genes were identified that contribute to citrus canker
      symptom development caused by X. citri subsp. citri. Among the 82 identified
      genes, 23 genes were classified as essential genes, as mutation of these genes
      caused severe reduction of bacterial growth in M9 medium. The remaining 59 genes
      were classified as putative virulence-related genes that include 32 previously
      reported virulence-related genes and 27 novel genes. The 32 known virulence
      related genes include genes that are involved in the type III secretion system
      (T3SS) and T3SS effectors, the quorum-sensing system, extracellular
      polysaccharide and lipopolysaccharide synthesis, and general metabolic pathways.
      The contribution to pathogenesis by nine genes (pthA4, trpG, trpC, purD, hrpM,
      peh-1, XAC1230, XAC1548, and XAC3049) was confirmed by complementation assays. We
      further validated the mutated genes and their phenotypes by analyzing the EZ-Tn5
      insertion copy number using Southern blot analysis. In conclusion, we have
      significantly advanced our understanding of the putative genetic determinants of
      the virulence mechanism of X. citri subsp. citri by identifying 59 putative
      virulence-related genes, including 27 novel genes.

PMID- 21899384
TI  - Establishing a biologic specimens repository for reproductive clinical trials:
      technical aspects.
AB  - The individual research group or independent investigator often requires access
      to samples from a unique well characterized subject population. Cohorts of such
      samples from a well-defined comparative population are rare and limited access
      can impede progress. This bottleneck can be removed by accessing the samples
      provided by biorepositories such as the NIH/NICHD Cooperative Reproductive
      Medicine Network (RMN) Biorepository (detailed in the preceeding manuscript in
      this issue. In those cases where the individual research group or independent
      investigator already has access to a unique population, comparisons between well
      defined groups are often sought to contextualize the data. In both cases seamless
      integration of data resources associated with the samples is required to ensure
      optimal comparisons. At the most basic level this requires standardization of
      sample collection and storage, as well as a de-identified data base containing
      demographic, clinical, and laboratory values. To facilitate such
      interoperability, the reagents and protocols that have been adopted by the RMN
      Biorepository for the collection and storage of serum, blood, saliva and sperm
      are described.

PMID- 21899386
TI  - Arbuscular mycorrhizal symbiosis limits foliar transcriptional responses to viral
      infection and favors long-term virus accumulation.
AB  - Tomato (Solanum lycopersicum) can establish symbiotic interactions with
      arbuscular mycorrhizal (AM) fungi, and can be infected by several pathogenic
      viruses. Here, we investigated the impact of mycorrhization by the fungus Glomus
      mosseae on the Tomato spotted wilt virus (TSWV) infection of tomato plants by
      transcriptomic and hormones level analyses. In TSWV-infected mycorrhizal plants,
      the AM fungus root colonization limited virus-induced changes in gene expression
      in the aerial parts. The virus-responsive upregulated genes, no longer induced in
      infected mycorrhizal plants, were mainly involved in defense responses and
      hormone signaling, while the virus-responsive downregulated genes, no longer
      repressed in mycorrhizal plants, were involved in primary metabolism. The
      presence of the AM fungus limits, in a salicylic acid-independent manner, the
      accumulation of abscissic acid observed in response to viral infection. At the
      time of the molecular analysis, no differences in virus concentration or symptom
      severity were detected between mycorrhizal and nonmycorrhizal plants. However, in
      a longer period, increase in virus titer and delay in the appearance of recovery
      were observed in mycorrhizal plants, thus indicating that the plant's reaction to
      TSWV infection is attenuated by mycorrhization.

PMID- 21899387
TI  - Effect of 'Candidatus Liberibacter solanacearum' on fitness of its insect vector,
      Bactericera cockerelli (Hemiptera: Triozidae), on tomato.
AB  - The potato/tomato psyllid, Bactericera cockerelli transmits the bacterium
      'Candidatus Liberibacter solanacearum', also known as 'Ca. L. psyllaurous', which
      causes zebra chip disease in solanaceous crops. There have been no studies
      addressing the effect of the bacterial plant pathogen on the biology of its
      insect vector. We examined several life-history traits, including 7-day
      fecundity, hatching percentage, incubation time, nymphal survival percentage,
      nymphal development time, total development time, and sex-ratio of 'Ca. L.
      solanacearum'-positive and -negative psyllid isofemale lines on tomato, as well
      as adult mortality index of 'Ca. L. solanacearum'-positive and -negative insects.
      The only two life-history traits that differed between the 'Ca. L. solanacearum'
      positive and -negative psyllid isofemale lines were 7-day fecundity and nymphal
      survival percentage, which were significantly lower in 'Ca. L. solanacearum'-
      positive lines. The symbiotic bacteria associated with both psyllid isofemale
      lines were similar, with the exception of 'Ca. L. solanacearum', which showed
      100% infection in the 'Ca. L. solanacearum'-positive lines and was not detected
      in the negative psyllid lines. These results suggest that 'Ca. L. solanacearum'
      has a negative effect on population growth rate of its insect vector on tomato.

PMID- 21899388
TI  - Variability in fusarium head blight epidemics in relation to global climate
      fluctuations as represented by the El Nino-Southern Oscillation and other
      atmospheric patterns.
AB  - Cross-spectral analysis was used to characterize the relationship between climate
      variability, represented by atmospheric patterns, and annual fluctuations of
      Fusarium head blight (FHB) disease intensity in wheat. Time series investigated
      were the Oceanic Nino Index (ONI), which is a measure of the El Nino-Southern
      Oscillation (ENSO), the Pacific-North American (PNA) pattern and the North
      Atlantic Oscillation (NAO), which are known to have strong influences on the
      Northern Hemisphere climate, and FHB disease intensity observations in Ohio from
      1965 to 2010 and in Indiana from 1973 to 2008. For each climate variable, mean
      climate index values for the boreal winter (December to February) and spring
      (March to May) were utilized. The spectral density of each time series and the
      (squared) coherency of each pair of FHB-climate-index series were estimated.
      Significance for coherency was determined by a nonparametric permutation
      procedure. Results showed that winter and spring ONI were significantly coherent
      with FHB in Ohio, with a period of about 5.1 years (as well as for some adjacent
      periods). The estimated phase-shift distribution indicated that there was a
      generally negative relation between the two series, with high values of FHB (an
      indication of a major epidemic) estimated to occur about 1 year following low
      values of ONI (indication of a La Nina); equivalently, low values of FHB were
      estimated to occur about 1 year after high values of ONI (El Nino). There was
      also limited evidence that winter ONI had significant coherency with FHB in
      Indiana. At periods between 2 and 7 years, the PNA and NAO indices were coherent
      with FHB in both Ohio and Indiana, although results for phase shift and period
      depended on the specific location, climate index, and time span used in
      calculating the climate index. Differences in results for Ohio and Indiana were
      expected because the FHB disease series for the two states were not similar.
      Results suggest that global climate indices and models could be used to identify
      potential years with high (or low) risk for FHB development, although the most
      accurate risk predictions will need to be customized for a region and will also
      require use of local weather data during key time periods for sporulation and
      infection by the fungal pathogen.

PMID- 21899389
TI  - Characterization of biofumigated Ralstonia solanacearum cells using micro-Raman
      spectroscopy and electron microscopy.
AB  - Essential oils of palmarosa, lemongrass, and eucalyptus have shown promise as
      biofumigants for control of the bacterial wilt disease of edible ginger (Zingiber
      officinale) caused by Ralstonia solanacearum race 4 in previous potting medium
      studies. Biochemical changes in R. solanacearum cells were evaluated with micro
      Raman spectroscopy following treatment with essential oils at different
      concentrations (0.04, 0.07, and 0.14% [vol/vol] of culture medium) and changes in
      cell structure were observed using electron microscopy. All treatments except
      palmarosa oil at 0.04% caused significant reductions in levels of amino acids,
      purine and pyrimidine bases of nucleic acids, carbohydrates, and lipids, as
      indicated by significant reduction in Raman peak heights at 621, 1,003, and 1,031
      inverse centimeters (cm(-1)) (phenylalanine); 643, 827, 852, 1,158, and 1,172 cm(
      1) (tyrosine); 758 cm(-1) (tryptophan); 725, 782, 1,337, and 1,578 cm(-1)
      (adenine, cytosine plus uracil, adenine, and adenine plus guanine, respectively);
      1,097 cm(-1) (carbohydrates); and 1,127, 1,450, and 2,932 cm(-1) (lipids)
      compared with untreated controls. Lemongrass oil treatments were the most
      effective in degrading cellular components. Scanning electron microscopy of
      palmarosa and lemongrass-oil-treated cells showed rupture of cell walls and cell
      debris but no degradation was noted for eucalyptus-oil-treated cells. Palmarosa-
      and lemongrass-oil-treated cells were positively stained with uranyl acetate when
      viewed by transmission electron microscopy whereas controls and eucalyptus-oil
      treated cells were negatively stained, indicating that the cell membranes were
      intact. The viability of eucalyptus-oil-treated cells was confirmed by cell
      culture following treatment. Micro-Raman spectroscopy is a powerful tool which
      can be further employed to better understand effects of fumigants and other
      bactericides on bacterial cells.

PMID- 21899390
TI  - Systemically induced resistance and microbial competitive exclusion: implications
      on biological control.
AB  - The root-knot nematode, Meloidogyne incognita, is among the most damaging
      agricultural pests, particularly to tomato. The mutualistic endophytes Fusarium
      oxysporum strain Fo162 (Fo162) and Rhizobium etli strain G12 (G12) have been
      shown to systemically induce resistance toward M. incognita. By using triple
      split-root tomato plants, spatially separated but simultaneous inoculation of
      both endophytes did not lead to additive reductions in M. incognita infection.
      More importantly, spatially separated inoculation of Fo162 and G12 led to a
      reduction in Fo162 root colonization of 35 and 39% when G12 was inoculated on a
      separate root section of the same plant in two independent experiments. In an
      additional split-root experiment, spatial separation of Fo162 and G12 resulted in
      a reduction of Fo162 root colonization of approximately 50% over the water
      controls in two independent experiments. The results suggested that the
      suppressive activity of G12 on Fo162 and M. incognita is possibly related to the
      induction of specific plant defense mechanisms. Thus, although Fo162 and G12 have
      the ability to systemically repress M. incognita infection in tomato, they can be
      considered incompatible biocontrol agents when both organisms are present
      simultaneously on the same root system.

PMID- 21899391
TI  - Intradermal injections of equine allogeneic umbilical cord-derived mesenchymal
      stem cells are well tolerated and do not elicit immediate or delayed
      hypersensitivity reactions.
AB  - BACKGROUND AIMS. The use of allogeneic mesenchymal stem cells (MSC) to treat
      acute equine lesions would greatly expand equine cellular therapy options;
      however, the safety and antigenicity of these cells have not been well-studied.
      We hypothesized that equine allogeneic umbilical cord tissue (UCT)-derived MSC
      would not elicit acute graft rejection or a delayed-type hypersensitivity
      response when injected intradermally. METHODS. Six Quarterhorse yearlings
      received 12 intradermal injections (autologous MSC, allogeneic MSC, positive
      control and negative control, in triplicate) followed by the same series of 12
      injections, 3-4 weeks later, at another site. Wheals were measured and palpated
      at 0.25, 4, 24, 48, 72 h and 7 days post-injection. Biopsies were obtained at 48
      and 72 h and 7 days post-injection. Mixed leukocyte reactions were performed 1
      week prior to the first injections and 3 weeks after the second injections.
      RESULTS. There were no adverse local or systemic responses to two intradermal
      injections of allogeneic MSC. MSC injection resulted in minor wheal formation,
      characterized by mild dermatitis, dermal edema and endothelial hyperplasia, that
      fully resolved by 48-72 h. No differences were noted between allogeneic and
      autologous MSC. The second injection of MSC did not elicit more significant
      physical or histomorphologic alterations compared with the first MSC injection.
      Neither allogeneic nor autologous UCT-derived MSC stimulated or suppressed
      baseline T-cell proliferation in vitro prior to or after two MSC administrations.
      CONCLUSIONS. Equine allogeneic UCT MSC may be safely administered intradermally
      on multiple occasions without eliciting a measurable cellular immune response.

PMID- 21899392
TI  - Correlation between serum linezolid concentration and the development of
      thrombocytopenia.
AB  - We evaluated the possible association between trough linezolid (LZD)
      concentrations and platelet counts using a dose-response curve with a logit model
      equation. We demonstrated that trough LZD concentrations correlated with platelet
      counts. A significant decrease in platelet count was observed in patients with
      trough LZD concentrations higher than 22.1 MUg/ml.

PMID- 21899393
TI  - Development of IMAGINE: a three-pillar student initiative to promote social
      accountability and interprofessional education.

PMID- 21899394
TI  - Language, power and implications for interprofessional collaboration: reflections
      on a transition from social work to medicine.

PMID- 21899395
TI  - A critical realist model of complexity for interprofessional working.
AB  - This paper presents a theoretical model of complexity for considering issues
      relevant to interprofessional working. The need for such a model is introduced
      with reference to the literature on collaboration and integration in health and
      social care, particularly in children's services. It is argued that
      interprofessional working is often seen as a response to complexity, but that
      current models fail to build an appreciation of complex causality into their
      approach to addressing needs through targeted interventions. The alternative
      offered here is a critical realist model based on Bhaskar's domains of reality,
      focusing on the implications of open systems, complex causality and contingency.
      These ideas are used to examine some of the issues and dilemmas typically
      encountered by interprofessional networks in coming together to work on complex
      cases.

PMID- 21899396
TI  - "Knowing more about the other professions clarified my own profession".
AB  - The purpose of this study was to compare which learning outcomes relating to an
      Interprofessional Training Unit (ITU) experience were found to be most important
      by students and by alumni. A cohort of 428 students in the ITU was asked to write
      three short statements describing the most important learning outcomes from the
      ITU. Alumni from the same cohort were after graduation asked the same question.
      Furthermore, they were asked to fill out a 12-item questionnaire. The statements
      concerning learning outcome were analysed qualitatively and categorized. The
      number of statements in each category was counted and tested for statistical
      difference between students and alumni. Students stated "uniprofessionalism" as
      the most important learning outcome followed by "interprofessionalism",
      "professional identity" and "learning environment". Alumni on the other hand
      stated "professional identity" as most important learning outcome followed with
      "interprofessionalism", "learning environment" and "uniprofessionalism". The
      study indicated that over time the perceived outcome of learning experiences from
      an ITU change in priority.

PMID- 21899397
TI  - Interprofessional education about patient decision support in specialty care.
AB  - Specialty care involves services provided by health professionals who focus on
      treating diseases affecting one body system. In contrast to primary care - aimed
      at providing continuous, comprehensive care - specialty care often involves
      intermittent episodes of care focused around specific medical conditions. In
      addition, it typically includes multiple providers who have unique areas of
      expertise that are important in supporting patients' care. Interprofessional care
      involves multiple professionals from different disciplines collaborating to
      provide an integrated approach to patient care. For patients to experience
      continuity of care across interprofessional providers, providers need to
      communicate and maintain a shared sense of responsibility to their patients. In
      this article, we describe challenges inherent in providing interprofessional
      patient decision support in specialty care. We propose ways for providers to
      engage in interprofessional decision support and discuss promising approaches to
      teaching an interprofessional decision support to specialty care providers.
      Additional evaluation and empirical research are required before further
      recommendations can be made about education for interprofessional decision
      support in specialty care.

PMID- 21899398
TI  - Simulated interprofessional education: an analysis of teaching and learning
      processes.
AB  - Simulated learning activities are increasingly being used in health professions
      and interprofessional education (IPE). Specifically, IPE programs are frequently
      adopting role-play simulations as a key learning approach. Despite this
      widespread adoption, there is little empirical evidence exploring the teaching
      and learning processes embedded within this type of simulation. This exploratory
      study provides insight into the nature of these processes through the use of
      qualitative methods. A total of 152 clinicians, 101 students and 9 facilitators
      representing a range of health professions, participated in video-recorded role
      plays and debrief sessions. Videotapes were analyzed to explore emerging issues
      and themes related to teaching and learning processes related to this type of
      interprofessional simulated learning experience. In addition, three focus groups
      were conducted with a subset of participants to explore perceptions of their
      educational experiences. Five key themes emerged from the data analysis:
      enthusiasm and motivation, professional role assignment, scenario realism,
      facilitator style and background and team facilitation. Our findings suggest that
      program developers need to be mindful of these five themes when using role-plays
      in an interprofessional context and point to the importance of deliberate and
      skilled facilitation in meeting desired learning outcomes.

PMID- 21899399
TI  - Interprofessional jargon: how is it exclusionary? Cultural determinants of
      language use in health care practice.
AB  - Language can impact significantly on the ways in which health care professionals
      relate and provide clinical services, as well as the way in which patients
      conceptualize their role in the healthcare encounter. The aim of this project was
      to explore the barriers and challenges to developing a collaborative approach in
      health care. A hermeneutic research approach was used with a convenience sample
      of international key informants representing 6 disciplines. A total of 10
      individual, semi-structured interviews were conducted. Findings emphasized the
      need to be more inclusive by avoiding the use of exclusionary jargon so that all
      members of the health care team, including patients and families, can adopt a
      collaborative practice orientation.

PMID- 21899400
TI  - Large-scale development of functional markers in Brassica species.
AB  - Numerous quantitative trait loci (QTL) have been detected in Brassica species,
      but fine-mapping of major QTL has advanced slowly. The development of functional
      markers can overcome this barrier. We used publicly available PlantGDB-assembled
      unique transcripts (PUTs) from Brassica species to design 7836 functional simple
      sequence repeat (SSR) primer pairs. Functional annotation of the PUTs containing
      SSRs was done by Blast2GO. The PUTs harbouring SSRs were mainly involved with
      nucleotide or protein binding and enzyme activity, and preferentially functioned
      in membranes and cytoplasm. Totally, 210 PUT primer pairs were selected to test
      their polymorphism, stability, and PCR quality. Approximately 70% (147) of the
      primer pairs resulted in successful amplification with an average polymorphic
      information content (PIC) value of 0.49. The highest level of polymorphism was
      dinucleotide repeat SSRs, followed by tri- and mononucleotide repeats.
      Approximately 60% of the primer pairs showed good transferability among Brassica
      species. These results show that the development of markers from PUTs is a
      feasible and simple approach to develop functional SSR markers on a large scale
      across Brassica species. In addition, these markers can provide a novel
      alternative that is a putative approach for rapid determination of candidate
      genes, genetic mapping, genetic diversity analysis, and comparative mapping in
      Brassica species.

PMID- 21899401
TI  - The influence of need for cognition and principal display panel factors on over
      the-counter drug facts label comprehension.
AB  - Nearly all work aimed at optimizing the ability of labeling to communicate over
      the-counter (OTC) drug information has focused on back-of-the-package
      characteristics, such as the Drug Facts label. The effects of front of the
      package, or principal display panel (PDP) factors, have largely been neglected by
      researchers. Similarly, heterogeneity in consumers' approach to new information
      has received scant attention in the context of OTC drugs. This preliminary study
      tested the hypothesis that display of a drug's brand name on the PDP and
      individuals' need for cognition influence comprehension of Drug Facts label
      information. University students (n = 212) that had experienced heartburn but not
      used the drug class being studied constituted the primary analysis cohort.
      Students were randomly assigned to review one of two PDPs (brand name or
      generic), followed by a Drug Facts label and a series of questions related to
      selection and usage of the drug. Participants with low need for cognition were
      influenced by the brand name PDP, as those exposed to a PDP featuring a brand
      (vs. generic) spent less time reading the Drug Facts label and demonstrated lower
      comprehension of the label information on proper drug selection. These findings
      suggest that further research is needed to understand the impact of PDP contents
      and cognitive characteristics of consumers on the communication of OTC drug
      information. Health care providers should consider communication strategies that
      account for the challenges patients face in using OTC drugs properly.

PMID- 21899402
TI  - Reframing motherhood through the culture-centered approach: articulations of
      agency among young Nepalese women.
AB  - Based upon the culture-centered approach that foregrounds the relevance of
      interrogating the taken-for-granted assumptions that circulate in the dominant
      models of health communication on family planning, this article argues that
      traditional approaches to reproductive health campaigns are concerned with safe
      motherhood (e.g., fertility, birth spacing, hospital delivery) rather than with
      the processes through which women construct, negotiate, and maintain meanings of
      motherhood and health within their cultural contexts. In doing so, this
      traditional framework leaves out the broader sociocultural, political, and
      economic contexts of social structures that constrain and enable the
      possibilities for health in the realm of motherhood. The culture-centered
      approach notes the erasure of these voices of women from dominant epistemic
      structures, and seeks to interrupt knowledge production by co-constructing
      meanings of reproductive health through dialogues with women at the margins.
      Therefore, in-depth interviews were conducted to centralize experiences of the
      cultural participants, allowing alternative health meanings to emerge within
      their local contexts. In particular, highlighting narratives of young Nepalese
      women living under poverty, we are able to understand how women actively
      (re)construct meanings of motherhood within their localized cultural spaces.

PMID- 21899403
TI  - Physician communication in the operating room: expanding application of face
      negotiation theory to the health communication context.
AB  - Communication variables that are associated with face-negotiation theory were
      examined in a sample of operating-room physicians. A survey was administered to
      anesthesiologists and surgeons at a teaching hospital in the southwestern United
      States to measure three variables commonly associated with face-negotiation
      theory: conflict-management style, face concern, and self-construal. The survey
      instrument that was administered to physicians includes items that measured these
      three variables in previous face-negotiation research with slight modification of
      item wording for relevance in the medical setting. The physician data were
      analyzed using confirmatory factor analysis, Pearson's correlations, and t-tests.
      Results of this initial investigation showed that variables associated with face
      negotiation theory were evident in the sample physician population. In addition,
      the correlations were similar among variables in the medical sample as those
      found in previous face-negotiation research. Finally, t-tests suggest variance
      between anesthesiologists and surgeons on specific communication variables. These
      findings suggest three implications that warrant further investigation with
      expanded sample size: (1) An intercultural communication theory and instrument
      can be utilized for health communication research; (2) as applied in a medical
      context, face-negotiation theory can be expanded beyond traditional intercultural
      communication boundaries; and (3) theoretically based communication structures
      applied in a medical context could help explain physician miscommunication in the
      operating room to assist future design of communication training programs for
      operating-room physicians.

PMID- 21899404
TI  - Using messages promoting descriptive norms to increase physical activity.
AB  - While it has been known for some time that what others do (i.e., normative
      behavior) can influence individual behavior, the effect of normative social
      influence on physical activity behavior has not been well established. The
      purpose of this study was to examine whether exposure to messages containing
      descriptive norm information about the prevalence of others' physical activity
      would affect individual physical activity behavior to a greater extent than
      exposure to nonnormative messages. Two independent studies were conducted. The
      first manipulated normative and nonnormative messages to examine effects on
      physical activity in office workers. Participants were assigned to one of four
      conditions (descriptive norm, health, appearance, or control) and received e-mail
      messages specific to their condition encouraging them to be active. It was
      hypothesized that participants in the descriptive norm condition would experience
      the greatest increase in physical activity, and the results supported this
      hypothesis for mild activity. A second study attempted to extend these results by
      examining the effect of descriptive norms on the activity behavior of university
      students, but no relationship was found. Typical activity levels and group
      identity with the reference group were suggested as possible explanations for the
      differing findings in these two studies.

PMID- 21899405
TI  - Dimethyl sulfoxide attenuates TNF-alpha-induced production of MMP-9 in human
      keratinocytes.
AB  - Dimethyl sulfoxide (DMSO), an aprotic solvent, is found to be useful as a topical
      agent with antioxidant effects in treatment of chronic wounds. However, the
      effects of DMSO on matrix metalloproteinase-9 (MMP-9) production in the presence
      of an inflammatory environment as in the case of disordered wound healing has not
      been previously investigated. The aim of this study was to investigate whether
      TNF-alpha-induced MMP-9 levels and MMP-9 mRNA expression from human keratinocytes
      (HaCaT) might be attenuated by DMSO. Human keratinocytes were treated with DMSO
      (0.1-1%) for 24 h and then exposed to tumor necrosis factor (TNF)-alpha (10
      ng/ml) for an additional 24 h. Expression and production of MMP-9 from HaCaT
      cells were determined by reverse transcription polymerase chain reaction (RT-PCR)
      and gelatin zymography, respectively. Results showed that DMSO inhibited
      production of both MMP-9 levels and MMP-9 mRNA expression in TNF-alpha-stimulated
      cells in a concentration-dependent manner. Inhibition of MMP-9 levels was
      statistically significant at DMSO concentrations of 0.75% and higher. Similarly,
      the increase of MMP-9 mRNA expression levels in TNF-alpha-stimulated cells was
      markedly reduced by DMSO. Data suggest that DMSO may attenuate the deleterious
      effects of MMP-9 through downregulation at the transcription level. Therefore,
      DMSO may provide a good strategy to prevent TNF-alpha-induced proteolytic
      activity in cutaneous inflammatory reactions.

PMID- 21899406
TI  - Determination of the effects of eNOS gene polymorphisms (T-786C and Glu298Asp) on
      nitric oxide levels in a methylmercury-exposed population.
AB  - Nitric oxide (NO) is a potent vasodilator with multiple protective effects
      involved in the regulation of cardiovascular functions. Endothelial NO synthase
      (eNOS) gene polymorphisms and environmental factors, such as mercury (Hg)
      exposure, may influence NO levels and increase the risk of cardiovascular damage.
      The aim of this study was to determine the role of the T-786C and Glu298Asp
      polymorphisms of the eNOS gene on nitrite concentrations following Hg exposure in
      humans. It was postulated that Hg exposure might decrease circulating nitrite
      concentrations and that variants in the eNOS gene might enhance the adverse
      effects of Hg resulting in increased risk of cardiovascular disease. Blood
      samples were collected from 202 volunteers exposed to methylmercury (MeHg)
      following fish consumption. Blood Hg concentrations (BHg) were determined by
      inductively coupled plasma-mass spectrometry and nitrite plasma concentration by
      a chemiluminescent method. The mean Hg concentration was 50.5 +/- 35.4 MUg/L and
      mean nitrite concentration was 251.4 +/- 106.3 nM. There were no significant
      differences in age, arterial blood pressure, body mass index, heart rate, and
      concentrations of Hg and nitrite concentrations between the genotype groups .
      When data were grouped together (TC + CC and TT group), there were still no
      marked differences. A multiple regression model indicated that decreased NO
      production was predominantly due to Hg, age, and gender. Polymorphisms did not
      seem to influence this effect. Our findings suggest that eNOS gene polymorphisms
      (T-786C and Glu298Asp) are not associated with an increased risk for
      cardiovascular diseases in MeHg-exposed subjects.

PMID- 21899407
TI  - Impact of repeated nicotine and alcohol coexposure on in vitro and in vivo
      chlorpyrifos dosimetry and cholinesterase inhibition.
AB  - Chlorpyrifos (CPF) is an organophosphorus insecticide, and neurotoxicity results
      from inhibition of acetylcholinesterase (AChE) by its metabolite, chlorpyrifos
      oxon. Routine consumption of alcohol and tobacco modifies metabolic and
      physiological processes impacting the metabolism and pharmacokinetics of other
      xenobiotics, including pesticides. This study evaluated the influence of repeated
      ethanol and nicotine coexposure on in vivo CPF dosimetry and cholinesterase (ChE)
      response (ChE- includes AChE and/or butyrylcholinesterase (BuChE)). Hepatic
      microsomes were prepared from groups of naive, ethanol-only (1 g/kg/d, 7 d, po),
      and ethanol + nicotine (1 mg/kg/d 7 d, sc)-treated rats, and the in vitro
      metabolism of CPF was evaluated. For in vivo studies, rats were treated with
      saline or ethanol (1 g/kg/d, po) + nicotine (1 mg/kg/d, sc) in addition to CPF (1
      or 5 mg/kg/d, po) for 7 d. The major CPF metabolite, 3,5,6-trichloro-2-pyridinol
      (TCPy), in blood and urine and the plasma ChE and brain acetylcholinesterase
      (AChE) activities were measured in rats. There were differences in
      pharmacokinetics, with higher TCPy peak concentrations and increased blood TCPy
      AUC in ethanol + nicotine groups compared to CPF only (approximately 1.8- and 3.8
      fold at 1 and 5 mg CPF doses, respectively). Brain AChE activities after ethanol
      + nicotine treatments showed significantly less inhibition following repeated 5
      mg CPF/kg dosing compared to CPF only (96 +/- 13 and 66 +/- 7% of naive at 4 h
      post last CPF dosing, respectively). Although brain AChE activity was minimal
      inhibited for the 1-mg CPF/kg/d groups, the ethanol + nicotine pretreatment
      resulted in a similar trend (i.e., slightly less inhibition). No marked
      differences were observed in plasma ChE activities due to the alcohol + nicotine
      treatments. In vitro, CPF metabolism was not markedly affected by repeated
      ethanol or both ethanol + nicotine exposures. Compared with a previous study of
      nicotine and CPF exposure, there were no apparent additional exacerbating effects
      due to ethanol coexposure.

PMID- 21899408
TI  - The acute and long-term effects of Middle East sand particles on the rat airway
      following a single intratracheal instillation.
AB  - Military personnel deployed in the Middle East have emphasized concerns regarding
      high levels of dust generated from blowing desert sand and the movement of troops
      and equipment. Airborne particulate matter levels (PM(10); PM < 10 MUm) in the
      region may exceed 1500 MUg/m(3), significantly higher than the military exposure
      guideline (MEG) of 50 MUg/m(3). Increases in PM(10) have been linked to a rise in
      incidences of asthma, obstructive pulmonary disease, lung cancer, and
      cardiovascular diseases. Male Sprague-Dawley rats received a single intratracheal
      (IT) instillation of 1, 5, or 10 mg of Middle East PM(10) collected at a military
      occupied site in Kuwait, silica (positive control), or titanium dioxide (TiO(2);
      negative control) suspended in 400 MUl sterile saline, or saline alone (vehicle
      control). Twenty-four hours, 3 d, 7 d and 6 mo postexposure (n = 15/group),
      organs including lung were evaluated for histopathological changes and for
      particle contaminants. Bronchoalveolar fluid (BALF) was also analyzed for
      cellular and biochemical parameters, including cytokines and chemokines.
      Instillation of silica resulted in early, pronounced, sustained inflammation
      indicated by significant increases in levels of total protein and neutrophils,
      and activities of lactate dehydrogenase activity and beta-glucuronidase activity.
      Lower magnitude and transient changes using the same markers were observed in
      animals exposed to TiO(2) and Middle East PM(10). The results suggest that for
      acute exposures, this Middle East PM(10) is a nuisance-type dust with relatively
      low toxicity. However, since average deployment of military personnel to the
      Middle East is 180 d with potential for multiple follow-on tours, chronic
      exposure studies are needed to fully understand the pulmonary effects associated
      with Middle East PM exposure.

PMID- 21899410
TI  - The challenges of intracranial revascularization for stroke prevention.

PMID- 21899411
TI  - Cancer mortality according to lipid-lowering drugs and lipoproteins in a general
      population.
AB  - OBJECTIVE: The beneficial effect of lipid-lowering drugs (LLD) on cardiovascular
      risk is established, but long term safety data remain scarce. Our aim was to
      assess 10-year risk of cancer mortality according to blood lipoprotein levels and
      LLD exposure, in a general population. METHODS: Our analysis was based on the
      Third French MONICA survey on cardiovascular risk factors (1994-1997).
      Participants were randomly recruited from the general population of three French
      areas and were aged 35-64 years. Subjects with a history of cancer at baseline
      were excluded from the analysis. Vital status and cause of mortality were
      obtained 10 years after inclusion. RESULTS: There were 3262 participants and 177
      deaths were recorded over the 10-year period (78 due to a cancer). The sample
      comprised 64% of normolipidaemic, 25% of untreated dyslipidaemic and 11% of
      dyslipidaemic subjects treated with LLD (4% statins, 6% fibrates and 1% other
      hypolipidaemic drugs). After adjustment for centre, age, gender, smoking, gamma
      glutamyl transpeptidase and mean corpuscular volume, the hazard ratios (HR) for
      cancer mortality in subjects with non-HDL cholesterol <3.5 mmol/L (135 mg/dL) and
      in those with HDL cholesterol <0.90 mmol/L (35 mg/dL) were 2.74 (95% confidence
      interval: 1.66-4.52, p < 0.001) and 2.83 (1.62-4.96, p < 0.001), respectively.
      The adjusted HR for cancer mortality was 0.31 (0.11-0.86, p = 0.025) in people on
      LLD compared to untreated subjects. CONCLUSIONS: In the present study, we confirm
      the significant association between low cholesterol and cancer mortality without
      finding any harmful signal regarding cancer risk associated with the use of LLD.
      The main limitations are remaining baseline differences between treated and
      untreated subjects (due to the observational design but minimized by the use of
      extensive adjustments and propensity score methods), and the lack of re
      assessment of LLD exposure and cholesterol levels during follow-up, possibly
      leading to a misclassification bias.

PMID- 21899412
TI  - Preface: Satellite workshop on comparative genomics, research in computational
      molecular biology (RECOMB-CG 2010).

PMID- 21899413
TI  - Consistency of sequence-based gene clusters.
AB  - In comparative genomics, differences or similarities of gene orders are
      determined to predict functional relations of genes or phylogenetic relations of
      genomes. For this purpose, various combinatorial models can be used to specify
      gene clusters--groups of genes that are co-located in a set of genomes. Several
      approaches have been proposed to reconstruct putative ancestral gene clusters
      based on the gene order of contemporary species. One prevalent and natural
      reconstruction criterion is consistency: For a set of reconstructed gene
      clusters, there should exist a gene order that comprises all given clusters. For
      permutation-based gene cluster models, efficient methods exist to verify this
      condition. In this article, we discuss the consistency problem for different gene
      cluster models on sequences with restricted gene multiplicities. Our results
      range from linear-time algorithms for the simple model of adjacencies to NP
      completeness proofs for more complex models like common intervals.

PMID- 21899414
TI  - A 2-approximation for the minimum duplication speciation problem.
AB  - We consider the following problem: given a set of gene family trees, spanning a
      given set of species, find a first speciation which splits these species into two
      subsets and minimizes the number of gene duplications that happened before this
      speciation. We call this problem the Minimum Duplication Bipartition Problem.
      Using a generalization of the Minimum Edge-Cut Problem, we propose a polynomial
      time 2-approximation algorithm for the Minimum Duplication Bipartition Problem.
      We apply this algorithm to the inference of species trees on synthetic datasets
      and on two datasets of eukaryotic species.

PMID- 21899415
TI  - A new genomic evolutionary model for rearrangements, duplications, and losses
      that applies across eukaryotes and prokaryotes.
AB  - Genomic rearrangements have been studied since the beginnings of modern genetics
      and models for such rearrangements have been the subject of many papers over the
      last 10 years. However, none of the extant models can predict the evolution of
      genomic organization into circular unichromosomal genomes (as in most
      prokaryotes) and linear multichromosomal genomes (as in most eukaryotes). Very
      few of these models support gene duplications and losses--yet these events may be
      more common in evolutionary history than rearrangements and themselves cause
      apparent rearrangements. We propose a new evolutionary model that integrates gene
      duplications and losses with genome rearrangements and that leads to genomes with
      either one (or a very few) circular chromosome or a collection of linear
      chromosomes. Our model is based on existing rearrangement models and inherits
      their linear-time algorithms for pairwise distance computation (for rearrangement
      only). Moreover, our model predictions fit observations about the evolution of
      gene family sizes and agree with the existing predictions about the growth in the
      number of chromosomes in eukaryotic genomes.

PMID- 21899416
TI  - Genome aliquoting revisited.
AB  - We prove that the genome aliquoting problem, the problem of finding a recent
      polyploid ancestor of a genome, with breakpoint distance can be solved in
      polynomial time. We propose an aliquoting algorithm that is a 2-approximation for
      the genome aliquoting problem with double cut and join distance, improving upon
      the previous best solution to this problem, Feijao and Meidanis' 4-approximation
      algorithm.

PMID- 21899417
TI  - The zero exemplar distance problem.
AB  - Given two genomes with duplicate genes, Zero Exemplar Distance is the problem of
      deciding whether the two genomes can be reduced to the same genome without
      duplicate genes by deleting all but one copy of each gene in each genome. Blin,
      Fertin, Sikora, and Vialette recently proved that Zero Exemplar Distance for
      monochromosomal genomes is NP-hard even if each gene appears at most two times in
      each genome, thereby settling an important open question on genome rearrangement
      in the exemplar model. In this article, we give a very simple alternative proof
      of this result. We also study the problem Zero Exemplar Distance for
      multichromosomal genomes without gene order, and prove the analogous result that
      it is also NP-hard even if each gene appears at most two times in each genome.
      For the positive direction, we show that both variants of Zero Exemplar Distance
      admit polynomial-time algorithms if each gene appears exactly once in one genome
      and at least once in the other genome. In addition, we present a polynomial-time
      algorithm for the related problem Exemplar Longest Common Subsequence in the
      special case that each mandatory symbol appears exactly once in one input
      sequence and at least once in the other input sequence. This answers an open
      question of Bonizzoni et al. We also show that Zero Exemplar Distance for
      multichromosomal genomes without gene order is fixed-parameter tractable in the
      general case if the parameter is the maximum number of chromosomes in each
      genome.

PMID- 21899418
TI  - Detecting highways of horizontal gene transfer.
AB  - In a horizontal gene transfer (HGT) event, a gene is transferred between two
      species that do not have an ancestor-descendant relationship. Typically, no more
      than a few genes are horizontally transferred between any two species. However,
      several studies identified pairs of species between which many different genes
      were horizontally transferred. Such a pair is said to be linked by a highway of
      gene sharing. We present a method for inferring such highways. Our method is
      based on the fact that the evolutionary histories of horizontally transferred
      genes disagree with the corresponding species phylogeny. Specifically, given a
      set of gene trees and a trusted rooted species tree, each gene tree is first
      decomposed into its constituent quartet trees and the quartets that are
      inconsistent with the species tree are identified. Our method finds a pair of
      species such that a highway between them explains the largest (normalized)
      fraction of inconsistent quartets. For a problem on n species and m input quartet
      trees, we give an efficient O(m + n(2))-time algorithm for detecting highways,
      which is optimal with respect to the quartets input size. An application of our
      method to a dataset of 1128 genes from 11 cyanobacterial species, as well as to
      simulated datasets, illustrates the efficacy of our method.

PMID- 21899419
TI  - Mapping association between long-range cis-regulatory regions and their target
      genes using synteny.
AB  - In chordates, long-range cis-regulatory regions are involved in the control of
      transcription initiation (either as repressors or enhancers). Their main
      characteristics are that (i) they can be located as far as 1 Mb away from the
      transcription start site of the target gene, (ii) they can regulate more than one
      gene, and (iii) they are usually orientation-independent. Therefore, proper
      characterization of functional interactions between long-range cis-regulatory
      regions and their target genes remains problematic. We present a novel method to
      predict such interactions based on the analysis of rearrangements between the
      human and 16 other vertebrate genomes. Our method is based on the assumption that
      genome rearrangements that would disrupt the functional interaction between a cis
      regulatory region and its target gene are likely to be deleterious. Therefore,
      conservation of synteny through evolution would be an indication of a functional
      interaction. We use our algorithm to predict the association between a set of
      123,905 human candidate regulatory regions to their target gene(s). This genome
      wide map of interactions has many potential applications, including the selection
      of candidate regions prior to in vivo experimental characterization, a better
      characterization of regulatory regions involved in position effect diseases, and
      an improved understanding of the mechanisms and importance of long-range
      regulation.

PMID- 21899420
TI  - Fast and accurate phylogenetic reconstruction from high-resolution whole-genome
      data and a novel robustness estimator.
AB  - The rapid accumulation of whole-genome data has renewed interest in the study of
      genomic rearrangements. Comparative genomics, evolutionary biology, and cancer
      research all require models and algorithms to elucidate the mechanisms, history,
      and consequences of these rearrangements. However, even simple models lead to NP
      hard problems, particularly in the area of phylogenetic analysis. Current
      approaches are limited to small collections of genomes and low-resolution data
      (typically a few hundred syntenic blocks). Moreover, whereas phylogenetic
      analyses from sequence data are deemed incomplete unless bootstrapping scores (a
      measure of confidence) are given for each tree edge, no equivalent to
      bootstrapping exists for rearrangement-based phylogenetic analysis. We describe a
      fast and accurate algorithm for rearrangement analysis that scales up, in both
      time and accuracy, to modern high-resolution genomic data. We also describe a
      novel approach to estimate the robustness of results-an equivalent to the
      bootstrapping analysis used in sequence-based phylogenetic reconstruction. We
      present the results of extensive testing on both simulated and real data showing
      that our algorithm returns very accurate results, while scaling linearly with the
      size of the genomes and cubically with their number. We also present extensive
      experimental results showing that our approach to robustness testing provides
      excellent estimates of confidence, which, moreover, can be tuned to trade off
      thresholds between false positives and false negatives. Together, these two novel
      approaches enable us to attack heretofore intractable problems, such as
      phylogenetic inference for high-resolution vertebrate genomes, as we demonstrate
      on a set of six vertebrate genomes with 8,380 syntenic blocks. A copy of the
      software is available on demand.

PMID- 21899421
TI  - Novel definition and algorithm for chaining fragments with proportional overlaps.
AB  - Chaining fragments is a crucial step in genome alignment. Existing chaining
      algorithms compute a maximum weighted chain with no overlaps allowed between
      adjacent fragments. In practice, using local alignments as fragments, instead of
      Maximal Exact Matches (MEMs), generates frequent overlaps between fragments, due
      to combinatorial reasons and biological factors, i.e., variable tandem repeat
      structures that differ in number of copies between genomic sequences. In this
      article, in order to raise this limitation, we formulate a novel definition of a
      chain, allowing overlaps proportional to the fragments lengths, and exhibit an
      efficient algorithm for computing such a maximum weighted chain. We tested our
      algorithm on a dataset composed of 694 genome pairs and accounted for significant
      improvements in terms of coverage, while keeping the running times below
      reasonable limits. Moreover, experiments with different ratios of allowed
      overlaps showed the robustness of the chains with respect to these ratios. Our
      algorithm is implemented in a tool called OverlapChainer (OC), which is available
      upon request to the authors.

PMID- 21899422
TI  - Robustness assessment of whole bacterial genome segmentations.
AB  - Comparison of closely related bacterial genomes has revealed the presence of
      highly conserved sequences forming a "backbone" that is interrupted by numerous,
      less conserved, DNA fragments. Segmentation of bacterial genomes into backbone
      and variable regions is particularly useful to investigate, among other things,
      bacterial genome evolution. Several software tools have been designed to compare
      complete bacterial chromosomes and a few online databases store pre-computed
      genome comparisons. However, very few statistical methods are available to
      evaluate the reliability of these software tools and to compare the results
      obtained with them. To fill this gap, we have developed two local scores to
      measure the robustness of bacterial genome segmentations. Our method uses a
      simulation procedure based on random perturbations of the compared genomes. The
      two scores described in this article provide useful information and are easy to
      implement, and their interpretation is intuitive. We show that they are suited to
      discriminate between robust and non-robust segmentations when genome aligners
      such as MAUVE and MGA are used.

PMID- 21899423
TI  - Double cut and join with insertions and deletions.
AB  - Many approaches to compute the genomic distance are still limited to genomes with
      the same content, without duplicated markers. However, differences in the gene
      content are frequently observed and can reflect important evolutionary aspects.
      While duplicated markers can hardly be handled by exact models, when duplicated
      markers are not allowed, a few polynomial time algorithms that include genome
      rearrangements, insertions and deletions were already proposed. In an attempt to
      improve these results, in the present work we give the first linear time
      algorithm to compute the distance between two multichromosomal genomes with
      unequal content, but without duplicated markers, considering insertions,
      deletions and double cut and join (DCJ) operations. We derive from this approach
      algorithms to sort one genome into another one also using DCJ operations,
      insertions and deletions. The optimal sorting scenarios can have different
      compositions and we compare two types of sorting scenarios: one that maximizes
      and one that minimizes the number of DCJ operations with respect to the number of
      insertions and deletions. We also show that, although the triangle inequality can
      be disrupted in the proposed genomic distance, it is possible to correct this
      problem adopting a surcharge on the number of non-common markers. We use our
      method to analyze six species of Rickettsia, a group of obligate intracellular
      parasites, and identify preliminary evidence of clusters of deletions.

PMID- 21899424
TI  - Genome halving and double distance with losses.
AB  - Given a phylogenetic tree involving whole genome duplication events, we
      contribute to solving the problem of computing the rearrangement and double cut
      and-join (DCJ) distances on a branch of the tree linking a duplication node d to
      a speciation node or a leaf s. In the case of a genome G at s containing exactly
      two copies of each gene, the genome halving problem is to find a perfectly
      duplicated genome D at d minimizing the rearrangement distance with G. We
      generalize the existing exact linear-time algorithm for genome halving to the
      case of a genome G with missing gene copies. In the case of a known ancestral
      duplicated genome D, we develop a greedy approach for computing the distance
      between G and D, called the double distance. Two algorithms are developed in both
      cases of a genome G containing exactly two copies of each gene, or at most two
      copies of each gene (with missing gene copies). These algorithms are shown time
      efficient and very accurate for both the rearrangement and DCJ distances.

PMID- 21899409
TI  - Stenting versus aggressive medical therapy for intracranial arterial stenosis.
AB  - BACKGROUND: Atherosclerotic intracranial arterial stenosis is an important cause
      of stroke that is increasingly being treated with percutaneous transluminal
      angioplasty and stenting (PTAS) to prevent recurrent stroke. However, PTAS has
      not been compared with medical management in a randomized trial. METHODS: We
      randomly assigned patients who had a recent transient ischemic attack or stroke
      attributed to stenosis of 70 to 99% of the diameter of a major intracranial
      artery to aggressive medical management alone or aggressive medical management
      plus PTAS with the use of the Wingspan stent system. The primary end point was
      stroke or death within 30 days after enrollment or after a revascularization
      procedure for the qualifying lesion during the follow-up period or stroke in the
      territory of the qualifying artery beyond 30 days. RESULTS: Enrollment was
      stopped after 451 patients underwent randomization, because the 30-day rate of
      stroke or death was 14.7% in the PTAS group (nonfatal stroke, 12.5%; fatal
      stroke, 2.2%) and 5.8% in the medical-management group (nonfatal stroke, 5.3%;
      non-stroke-related death, 0.4%) (P=0.002). Beyond 30 days, stroke in the same
      territory occurred in 13 patients in each group. Currently, the mean duration of
      follow-up, which is ongoing, is 11.9 months. The probability of the occurrence of
      a primary end-point event over time differed significantly between the two
      treatment groups (P=0.009), with 1-year rates of the primary end point of 20.0%
      in the PTAS group and 12.2% in the medical-management group. CONCLUSIONS: In
      patients with intracranial arterial stenosis, aggressive medical management was
      superior to PTAS with the use of the Wingspan stent system, both because the risk
      of early stroke after PTAS was high and because the risk of stroke with
      aggressive medical therapy alone was lower than expected. (Funded by the National
      Institute of Neurological Disorders and Stroke and others; SAMMPRIS
      ClinicalTrials.gov number, NCT00576693.).

PMID- 21899425
TI  - Listing all parsimonious reversal sequences: new algorithms and perspectives.
AB  - In comparative genomics studies, finding a minimum length sequences of reversals,
      so-called sorting by reversals, has been the topic of a huge literature. Since
      there are many minimum length sequences, another important topic has been the
      problem of listing all parsimonious sequences between two genomes, called the All
      Sorting Sequences by Reversals (ASSR) problem. In this article, we revisit the
      ASSR problem for uni-chromosomal genomes when no duplications are allowed and
      when the relative order of the genes is known. We put the current body of work in
      perspective by illustrating the fundamental framework that is common for all of
      them, a perspective that allows us for the first time to theoretically compare
      their running times. The article also proposes an improved framework that
      empirically speeds up all known algorithms.

PMID- 21899426
TI  - An algorithm to solve the motif alignment problem for approximate nested tandem
      repeats in biological sequences.
AB  - An approximate nested tandem repeat (NTR) in a string T is a complex repetitive
      structure consisting of many approximate copies of two substrings x and X
      ("motifs") interspersed with one another. NTRs fall into a class of repetitive
      structures broadly known as subrepeats. NTRs have been found in real DNA
      sequences and are expected to be important in evolutionary biology, both in
      understanding evolution of the ribosomal DNA (where NTRs can occur), and as a
      potential marker in population genetic and phylogenetic studies. This article
      describes an alignment algorithm for the verification phase of the software tool
      NTRFinder developed for database searches for NTRs. When the search algorithm has
      located a subsequence containing a possible NTR, with motifs X and x, a
      verification step aligns this subsequence against an exact NTR built from the
      templates X and x, to determine whether the subsequence contains an approximate
      NTR and its extent. This article describes an algorithm to solve this alignment
      problem in O(|T|(|X| + |x|)) space and time. The algorithm is based on Fischetti
      et al.'s wrap-around dynamic programming.

PMID- 21899427
TI  - Theory and practice of ultra-perfection.
AB  - Perfection has been used as a criteria to classify rearrangement scenarios since
      2004. However, there is a fundamental bias towards extant species in the original
      definition: ancestral species are not bound to perfection. Here we develop a new
      theory of perfection that takes an egalitarian view of species, and we examine
      the fitness of this theory on several datasets. Supplementary Material is
      available at www.liebertonline.com/cmb.

PMID- 21899428
TI  - Restricted DCJ model: rearrangement problems with chromosome reincorporation.
AB  - We study three classical problems of genome rearrangement--sorting, halving, and
      the median problem--in a restricted double cut and join (DCJ) model. In the DCJ
      model, introduced by Yancopoulos et al., we can represent rearrangement events
      that happen in multichromosomal genomes, such as inversions, translocations,
      fusions, and fissions. Two DCJ operations can mimic transpositions or block
      interchanges by first extracting an appropriate segment of a chromosome, creating
      a temporary circular chromosome, and then reinserting it in its proper place. In
      the restricted model, we are concerned with multichromosomal linear genomes and
      we require that each circular excision is immediately followed by its
      reincorporation. Existing linear-time DCJ sorting and halving algorithms ignore
      this reincorporation constraint. In this article, we propose a new algorithm for
      the restricted sorting problem running in O(n log n) time, thus improving on the
      known quadratic time algorithm. We solve the restricted halving problem and give
      an algorithm that computes a multilinear halved genome in linear time. Finally,
      we show that the restricted median problem is NP-hard as conjectured.

PMID- 21899429
TI  - The complexity of the gapped consecutive-ones property problem for matrices of
      bounded maximum degree.
AB  - The Gapped Consecutive-Ones Property (C1P) Problem, or the (k, delta)-C1P Problem
      is: given a binary matrix M and integers k and delta, decide if the columns of M
      can be ordered such that each row contains at most k blocks of 1's, and no two
      neighboring blocks of 1's are separated by a gap of more than delta 0's. This
      problem was introduced by Chauve et al. ( 2009b ). The classical polynomial-time
      solvable C1P Problem is equivalent to the (1, 0)-C1P problem. It has been shown
      that, for every unbounded or bounded k >= 2 and unbounded or bounded delta >= 1,
      except when (k, delta) = (2, 1), the (k, delta)-C1P Problem is NP-complete
      (Manuch et al., 2011 ; Goldberg et al., 1995 ). In this article, we study the
      Gapped C1P Problem with a third parameter d, namely the bound on the maximum
      number of 1's in any row of M, or the bound on the maximum degree of M. This is
      motivated by the reconstruction of ancestral genomes (Ma et al., 2006 ; Chauve
      and Tannier, 2008 ), where, in binary matrices obtained from the experiments of
      Chauve and Tannier ( 2008 ), we have observed that the majority of the rows have
      low degree, while each high degree row contains many rows of low degree. The (d,
      k, delta)-C1P Problem has been shown to be polynomial-time solvable when all
      three parameters are fixed (Chauve et al., 2009b ). Since fixing d also fixes k
      (k <= d), the only case left to consider is the case when delta is unbounded, or
      the (d, k, infinity)-C1P Problem. Here we show that for every d > k >= 2, the (d,
      k, infinity)-C1P Problem is NP-complete.

PMID- 21899430
TI  - Efficient computation of approximate gene clusters based on reference
      occurrences.
AB  - Whole genome comparison based on the analysis of gene cluster conservation has
      become a popular approach in comparative genomics. While gene order and gene
      content as a whole randomize over time, it is observed that certain groups of
      genes which are often functionally related remain co-located across species.
      However, the conservation is usually not perfect which turns the identification
      of these structures, often referred to as approximate gene clusters, into a
      challenging task. In this article, we present an efficient set distance based
      approach that computes approximate gene clusters by means of reference
      occurrences. We show that it yields highly comparable results to the
      corresponding non-reference based approach, while its polynomial runtime allows
      for approximate gene cluster detection in parameter ranges that used to be
      feasible only with simpler, e.g., max-gap based, gene cluster models. To
      illustrate further the performance and predictive power of our algorithm, we
      compare it to a state-of-the art approach for max-gap gene cluster computation.

PMID- 21899431
TI  - Feasibility and efficacy of isoniazid prophylaxis for latent tuberculosis in HIV
      infected clients patients in Thailand.
AB  - A prospective study was conducted in 4339 HIV-positive clients at the Thai Red
      Cross AIDS Research Centre (TRC-ARC) Anonymous clinic, Bangkok, Thailand between
      January 2003 and April 2008. A tuberculin skin test (TST) was done for all
      patients without a previous history of tuberculosis (TB). Nine months of
      isoniazid (INH) was given for all positive TST/no active TB. TST-negative clients
      were asked to repeat the TST annually. The study aim was to evaluate the
      feasibility and efficacy of INH prophylaxis for preventing TB in HIV-positive
      Thai patients. Of those patients, 4111 (94.7%) had a TST done; 1157 (28.1%) were
      TST positive and 799 patients started INH prophylaxis. In all, 551 (69%) and 633
      (79.2%) patients completed 9 months and 6 months of INH, respectively; 176
      (20.2%) patients had a negative TST at baseline and subsequently converted to
      positive. Only patients with a baseline CD4 >200 cells/MUL (p=0.000) and
      currently on antiretroviral (ARV) treatment (p=0.000) were related to having a
      positive TST. This baseline CD4 level was also significantly related to higher
      INH completion rates at 6 months (p=0.000). Interestingly, none of INH completion
      patients developed active TB. The feasibility of INH prophylaxis in TST-positive
      patients in this setting is possible. However, the long-term advantage of INH
      prophylaxis in terms of TB prevention, especially in HIV-1-infected patients on
      highly active antiretroviral therapy (HAART), is still an issue that needs more
      research.

PMID- 21899432
TI  - Overexpression of manganese superoxide dismutase does not increase clonogenic
      cell survival despite effect on apoptosis in irradiated lymphoblastoid cells.
AB  - Gene therapy-mediated overexpression of superoxide dismutases (SOD) appears to be
      a promising strategy for modulating radiosensitivity based on detoxification of
      superoxide radicals and suppression of apoptosis. Using recombinant lentiviral
      based vectors, the effects of SOD overexpression on both were tested in human
      lymphoblastoid cells (TK6) that are sensitive to radiation-induced apoptosis. TK6
      cells were transduced with vectors containing CuZnSOD, MnSOD or inverted MnSOD
      (MSODi) cDNA. Gene transfer efficiency, SOD activity, superoxide-radical
      resistance, apoptosis and clonogenic survival were determined. A six- to
      eightfold increase in SOD activity was observed after transduction, rendering
      MnSOD-overexpressing TK6 cells significantly more resistant to paraquat-induced
      superoxide radical production than controls. Although significant differences in
      sensitivity to apoptosis were observed for MnSOD, no differences in clonogenic
      survival after irradiation were detected between any groups. Our data show that
      efficient cellular SOD overexpression, an increased superoxide radical
      detoxifying ability and, for MnSOD, decreased apoptosis did not result in
      increased clonogenic survival after irradiation. This strengthens the hypothesis
      of differences in the radiation-modulating effects of SOD on normal and malignant
      cells (protective and nonprotective, respectively), thereby showing its potential
      to increase the therapeutic index in future clinical SOD-based radioprotection
      approaches.

PMID- 21899433
TI  - Sesamol as a potential radioprotective agent: in vitro studies.
AB  - Protection against radiation-induced DNA strand breaks is an important aspect in
      the design and development of a radioprotector. In this study, the
      radioprotective efficacy of sesamol, a natural antioxidant, was investigated in
      aqueous solution of plasmid DNA (pBR322) and compared with that of melatonin, a
      known antioxidant-based radioprotector. Thermal denaturation studies on
      irradiated calf thymus DNA were also carried out with sesamol and melatonin.
      Sesamol demonstrated greater radioprotective efficacy in both plasmid DNA and
      calf thymus DNA. To assess the radical scavenging capacity of sesamol and
      melatonin, 2-deoxyribose degradation, DPPH and ABTS assays were performed.
      Sesamol exhibited more scavenging capacity compared to melatonin. In vitro
      studies with V79 cells showed that sesamol is 20 times more potent than
      melatonin. It is proposed that the greater radioprotective efficacy of sesamol
      could be due to its greater capacity for scavenging of free radicals compared to
      melatonin. The results will be helpful in understanding the mechanisms and
      development of sesamol as a radioprotector.

PMID- 21899434
TI  - Influence of risk and protective factors on substance use outcomes across
      developmental periods: a comparison of youth and young adults.
AB  - Data were collected from samples of youth (ages 11-18; N = 38,268) and young 10
      adults (ages 18-24; N = 602) across 30 Tennessee counties using surveys and
      telephone interviews conducted in 2006-2008. Data were analyzed using
      hierarchical nonlinear modeling to determine: (1) which risk and protective
      factors predicted alcohol and marijuana use, and (2) whether predictors differed
      as a function of developmental period. Findings provide preliminary evidence that
      prevention efforts need to take into consideration the changing environment and
      related influences as youth age, especially as they move from a more protected
      community environment to one where they live somewhat independently. Implications
      and limitations are discussed.

PMID- 21899435
TI  - Agroinoculation of Citrus tristeza virus causes systemic infection and symptoms
      in the presumed nonhost Nicotiana benthamiana.
AB  - Citrus tristeza virus (CTV) naturally infects only some citrus species and
      relatives and within these it only invades phloem tissues. Failure to agroinfect
      citrus plants and the lack of an experimental herbaceous host hindered
      development of a workable genetic system. A full-genome cDNA of CTV isolate T36
      was cloned in binary plasmids and was used to agroinfiltrate Nicotiana
      benthamiana leaves, with or without coinfiltration with plasmids expressing
      different silencing-suppressor proteins. A time course analysis in
      agroinfiltrated leaves indicated that CTV accumulates and moves cell-to-cell for
      at least three weeks postinoculation (wpi), and then, it moves systemically and
      infects the upper leaves with symptom expression. Silencing suppressors expedited
      systemic infection and often increased infectivity. In systemically infected
      Nicotiana benthamiana plants, CTV invaded first the phloem, but after 7 wpi, it
      was also found in other tissues and reached a high viral titer in upper leaves,
      thus allowing efficient transmission to citrus by stem-slash inoculation.
      Infected citrus plants showed the symptoms, virion morphology, and phloem
      restriction characteristic of the wild T36 isolate. Therefore, agroinfiltration
      of Nicotiana benthamiana provided the first experimental herbaceous host for CTV
      and an easy and efficient genetic system for this closterovirus.

PMID- 21899436
TI  - Nonhost resistance of rice to rust pathogens.
AB  - Rice is atypical in that it is an agricultural cereal that is immune to fungal
      rust diseases. This report demonstrates that several cereal rust species
      (Puccinia graminis f. sp tritici, P. triticina, P. striiformis, and P. hordei)
      can infect rice and produce all the infection structures necessary for plant
      colonization, including specialized feeding cells (haustoria). Some rust
      infection sites are remarkably large and many plant cells are colonized,
      suggesting that nutrient uptake occurs to support this growth. Rice responds with
      an active, nonhost resistance (NHR) response that prevents fungal sporulation and
      that involves callose deposition, production of reactive oxygen species, and,
      occasionally, cell death. Genetic variation for the efficacy of NHR to wheat stem
      rust and wheat leaf rust was observed. Unlike cereal rusts, the rust pathogen
      (Melampsora lini) of the dicotyledenous plant flax (Linum usitatissimum) rarely
      successfully infects rice due to an apparent inability to recognize host-derived
      signals. Morphologically abnormal infection structures are produced and
      appressorial-like structures often don't coincide with stomata. These data
      suggest that basic compatibility is an important determinate of nonhost infection
      outcomes of rust diseases on cereals, with cereal rusts being more capable of
      infecting a cereal nonhost species compared with rust species that are adapted
      for dicot hosts.

PMID- 21899437
TI  - A novel multidomain polyketide synthase is essential for zeamine production and
      the virulence of Dickeya zeae.
AB  - Dickeya zeae is the causal agent of the rice foot rot disease, but its mechanism
      of infection remains largely unknown. In this study, we identified and
      characterized a novel gene designated as zmsA. The gene encodes a large protein
      of 2,346 amino acids in length, which consists of multidomains arranged in the
      order of N-terminus, beta-ketoacyl synthase, acyl transferase, acyl carrier
      protein, beta-ketoacyl reductase, dehydratase. This multidomain structure and
      sequence alignment analysis suggest that ZmsA is a member of the polyketide
      synthase family. Mutation of zmsA abolished antimicrobial activity and attenuated
      the virulence of D. zeae. To determine the relationship between antimicrobial
      activity and virulence, active compounds were purified from D. zeae EC1 and were
      structurally characterized. This led to identification of two polyamino
      compounds, i.e., zeamine and zeamine II, that were phytotoxins and potent
      antibiotics. These results have established the essential role of ZmsA in zeamine
      biosynthesis and presented a new insight on the molecular mechanisms of D. zeae
      pathogenicity.

PMID- 21899439
TI  - HflB gene-based phytopathogenic classification of 'Candidatus phytoplasma mali'
      strains and evidence that strain composition determines virulence in multiply
      infected apple trees.
AB  - Analysis of pathological and molecular data of 'Candidatus Phytoplasma mali'
      accessions from 27 apple trees differing considerably in symptomatology was used
      to molecularly characterize and classify strains of the infecting apple
      proliferation phytoplasma. Single-strand conformation polymorphism and sequence
      analysis of a variable fragment of ATP00464-type hflB gene revealed that these
      sources consisted of single-strain and multiple-strain accessions that occurred
      in similar numbers. The latter group was composed of two to five distinct
      strains. Analysis of cloned sequences of mild and severe single-strain accessions
      resulted in two groups of reads that clustered, according to their virulence,
      distantly in the phylogram. Based on this data, the clustering patterns of
      multiple-strain accession sequences indicated that nearly all of them were
      composed of mild and severe strains. The distinct clustering of sequences
      representing mild and severe strains was associated with a range of molecular
      markers at the nucleotide and amino acid level. Data indicate that the virulence
      of multiple-strain accessions is determined by the ratio of the occurring mild
      and severe strains in that mild accessions were characterized by the predominance
      of sequences representing mild strains and vice versa. There is evidence that
      shifts in the population and other events may occur that drastically alter
      virulence of multiple-strain accessions.

PMID- 21899438
TI  - A high level of transgenic viral small RNA is associated with broad potyvirus
      resistance in cucurbits.
AB  - Gene-silencing has been used to develop resistance against many plant viruses but
      little is known about the transgenic small-interfering RNA (t-siRNA) that confers
      this resistance. Transgenic cucumber and melon lines harboring a hairpin
      construct of the Zucchini yellow mosaic potyvirus (ZYMV) HC-Pro gene accumulated
      different levels of t-siRNA (6 to 44% of total siRNA) and exhibited resistance to
      systemic ZYMV infection. Resistance to Watermelon mosaic potyvirus and Papaya
      ring spot potyvirus-W was also observed in a cucumber line that accumulated high
      levels of t-siRNA (44% of total siRNA) and displayed significantly increased
      levels of RNA-dependent RNA (RDR)1 and Argonaute 1, as compared with the other
      transgenic and nontransformed plants. The majority of the t-siRNA sequences were
      21 to 22 nucleotides in length and sense strand biased. The t-siRNA were not
      uniformly distributed throughout the transgene but concentrated in "hot spots" in
      a pattern resembling that of the viral siRNA peaks observed in ZYMV-infected
      cucumber and melon. Mutations in ZYMV at the loci associated with the siRNA peaks
      did not break this resistance, indicating that hot spot t-siRNA may not be
      essential for resistance. This study shows that resistance based on gene
      silencing can be effective against related viruses and is probably correlated
      with t-siRNA accumulation and increased expression of RDR1.

PMID- 21899440
TI  - Sulfur-oxidizing chemolithotrophic proteobacteria dominate the microbiota in high
      arctic thermal springs on Svalbard.
AB  - The thermal springs Trollosen and Fisosen, located on the High Arctic archipelago
      Svalbard, discharge saline groundwaters rich in hydrogen sulfide and ammonium
      through a thick layer of permafrost. Large amounts of biomass that consist of
      filamentous microorganisms containing sulfur granules, as analyzed with energy
      dispersive X-ray analysis, were found in the outflow. Prokaryotic 16S rRNA gene
      libraries and quantitative polymerase chain reaction (qPCR) analyses reported
      bacteria of the gamma- and E-proteobacterial classes as the dominant organisms in
      the filaments and the planktonic fractions, closely related to known
      chemolithoautotrophic sulfur oxidizers (Thiotrix and Sulfurovum). Archaea
      comprised ~1% of the microbial community, with the majority of sequences
      affiliated with the Thaumarchaeota. Archaeal and bacterial genes coding for a
      subunit of the enzyme ammonia monooxygenase (amoA) were detected, as well as 16S
      rRNA genes of Nitrospira, all of which is indicative of potential complete
      nitrification in both springs. 16S rRNA sequences related to methanogens and
      methanotrophs were detected as well. This study provides evidence that the
      microbial communities in Trollosen and Fisosen are sustained by chemolithotrophy,
      mainly through the oxidation of reduced sulfur compounds, and that ammonium and
      methane might be minor, additional sources of energy and carbon.

PMID- 21899442
TI  - DNA repair gene 8-oxoguanine DNA glycosylase Ser326Cys polymorphism and
      colorectal cancer risk in a Kashmiri population.
AB  - 8-Oxoguanine DNA glycosylase (OGG1) is one of the important base excision repair
      enzymes that repair 8-oxoguanine lesion incorporated within the DNA of an
      individual by reactive oxygen species. The aim of this study was to detect the
      role of OGG1 Ser326Cys polymorphism in susceptibility to colorectal cancer (CRC)
      in a Kashmiri population. We investigated the genotype distribution of the OGG1
      gene in 114 CRC cases in comparison with 200 healthy subjects. There was no
      significant association between OGG1 Ser326Cys polymorphism and CRC, but the
      homozygous Cys/Cys variant genotype was associated with an increased risk of
      colon cancer (p<0.05). This study suggests that the OGG1 polymorphism is not
      associated with the risk of development of CRC in the Kashmiri population in
      general but modulates the risk of cancer development in colon via interaction
      with many dietary factors.

PMID- 21899441
TI  - Frequency Determination of alpha-1,3 Glucosyltransferase p.Y131H and p.F304S
      Polymorphisms in the Croatian Population Revealed Five Novel Single Nucleotide
      Polymorphisms in the hALG6 Gene.
AB  - The congenital disorder of glycosylation (CDG)-Ic (ALG6-CDG, CDG-Ic) is caused by
      mutations in the hALG6 gene that encodes the N-glycosylation pathway enzyme,
      alpha-1,3-glucosyltransferase (NP_037471.2). The aim of our study was to estimate
      the frequencies of ALG6-CDG related p.Y131H and p.F304S polymorphisms in the
      Croatian population. Genomic DNA was isolated from blood samples collected from
      600 healthy individuals. Functional single-nucleotide polymorphisms rs35383149
      and rs17856039 causing p.Y131H and p.F304S, respectively, were genotyped by the
      TaqMan method and direct sequencing. The frequency of p.F304S polymorphism in the
      studied cohort was shown to be similar to the frequencies found in other tested
      populations (27%), whereas the frequency of p.Y131H was found to be three times
      higher (6.7%). Five novel base substitutions in the hALG6 gene were also found:
      three in exon 5 (c.383T>C, c.390G>A, and c.429G>C) and two in a downstream
      intervening sequence (IVS5+17C/T and IVS5+34G/A).

PMID- 21899443
TI  - Health care reform and the health care workforce--the Massachusetts experience.
AB  - Massachusetts' experience with health care reform may be predictive of the
      effects of national health care reform. Data on employment in the health care
      industry were examined to determine the impact of the Massachusetts reform on the
      state's health care workforce.

PMID- 21899444
TI  - Massachusetts' health care reform and emergency department utilization.

PMID- 21899445
TI  - The uncertain future of Medicare and graduate medical education.

PMID- 21899446
TI  - Images in clinical medicine. Chemotherapy-induced hyperpigmentation of the
      tongue.

PMID- 21899447
TI  - HIV vaccine development--improving on natural immunity.

PMID- 21899448
TI  - Global noncommunicable diseases--lessons from the HIV-AIDS experience.

PMID- 21899449
TI  - Drunk driving, distracted driving, moralism, and public health.

PMID- 21899450
TI  - Genetic basis for in vivo daptomycin resistance in enterococci.
AB  - BACKGROUND: Daptomycin is a lipopeptide with bactericidal activity that acts on
      the cell membrane of enterococci and is often used off-label to treat patients
      infected with vancomycin-resistant enterococci. However, the emergence of
      resistance to daptomycin during therapy threatens its usefulness. METHODS: We
      performed whole-genome sequencing and characterization of the cell envelope of a
      clinical pair of vancomycin-resistant Enterococcus faecalis isolates from the
      blood of a patient with fatal bacteremia; one isolate (S613) was from blood drawn
      before treatment and the other isolate (R712) was from blood drawn after
      treatment with daptomycin. The minimal inhibitory concentrations (MICs) of these
      two isolates were 1 and 12 MUg per milliliter, respectively. Gene replacements
      were made to exchange the alleles found in isolate S613 with those in isolate
      R712. RESULTS: Isolate R712 had in-frame deletions in three genes. Two genes
      encoded putative enzymes involved in phospholipid metabolism, GdpD (which denotes
      glycerophosphoryl diester phosphodiesterase) and Cls (which denotes cardiolipin
      synthetase), and one gene encoded a putative membrane protein, LiaF (which
      denotes lipid II cycle-interfering antibiotics protein but whose exact function
      is not known). LiaF is predicted to be a member of a three-component regulatory
      system (LiaFSR) involved in the stress-sensing response of the cell envelope to
      antibiotics. Replacement of the liaF allele of isolate S613 with the liaF allele
      from isolate R712 quadrupled the MIC of daptomycin, whereas replacement of the
      gdpD allele had no effect on MIC. Replacement of both the liaF and gdpD alleles
      of isolate S613 with the liaF and gdpD alleles of isolate R712 raised the
      daptomycin MIC for isolate S613 to 12 MUg per milliliter. As compared with
      isolate S613, isolate R712--the daptomycin-resistant isolate--had changes in the
      structure of the cell envelope and alterations in membrane permeability and
      membrane potential. CONCLUSIONS: Mutations in genes encoding LiaF and a GdpD
      family protein were necessary and sufficient for the development of resistance to
      daptomycin during the treatment of vancomycin-resistant enterococci. (Funded by
      the National Institute of Allergy and Infectious Diseases and the National
      Institutes of Health.).

PMID- 21899451
TI  - General and abdominal obesity and risk of death among black women.
AB  - BACKGROUND: Recent pooled analyses show an increased risk of death with
      increasing levels of the body-mass index (BMI, the weight in kilograms divided by
      the square of the height in meters) of 25.0 or higher in populations of European
      ancestry, a weaker association among East Asians, and no association of an
      increased BMI with an increased risk of death among South Asians. The limited
      data available on blacks indicate that the risk of death is increased only at
      very high levels of BMI (>=35.0). METHODS: We prospectively assessed the relation
      of both BMI and waist circumference to the risk of death among 51,695 black women
      with no history of cancer or cardiovascular disease who were 21 to 69 years of
      age at study enrollment. Our analysis was based on follow-up data from 1995
      through 2008 in the Black Women's Health Study. Multivariable proportional
      hazards models were used to estimate hazard ratios and 95% confidence intervals.
      RESULTS: Of 1773 deaths identified during follow-up, 770 occurred among 33,916
      women who had never smoked. Among nonsmokers, the risk of death was lowest for a
      BMI of 20.0 to 24.9. For a BMI above this range, the risk of death increased as
      the BMI increased. With a BMI of 22.5 to 24.9 as the reference category,
      multivariable-adjusted hazard ratios were 1.12 (95% confidence interval [CI],
      0.87 to 1.44) for a BMI of 25.0 to 27.4, 1.31 (95% CI, 1.01 to 1.72) for a BMI of
      27.5 to 29.9, 1.27 (95% CI, 0.99 to 1.64) for a BMI of 30.0 to 34.9, 1.51 (95%
      CI, 1.13 to 2.02) for a BMI of 35.0 to 39.9, and 2.19 (95% CI, 1.62 to 2.95) for
      a BMI of 40.0 to 49.9 (P<0.001 for trend). A large waist circumference was
      associated with an increased risk of death from any cause among women with a BMI
      of less than 30.0. CONCLUSIONS: The risk of death from any cause among black
      women increased with an increasing BMI of 25.0 or higher, which is similar to the
      pattern observed among whites. Waist circumference appeared to be associated with
      an increased risk of death only among nonobese women. (Funded by the National
      Cancer Institute.).

PMID- 21899452
TI  - Drug-resistant epilepsy.

PMID- 21899453
TI  - Mendelian disorders of membrane trafficking.

PMID- 21899454
TI  - Images in clinical medicine. Ortner's syndrome.

PMID- 21899455
TI  - Case records of the Massachusetts General Hospital. Case 27-2011. A 17-year-old
      boy with abdominal pain and weight loss.

PMID- 21899456
TI  - What has kept the antibiotic miracle alive?

PMID- 21899457
TI  - Illuminating immune privilege--a role for regulatory T cells in preventing
      rejection.

PMID- 21899458
TI  - Transcatheter aortic-valve replacement.

PMID- 21899460
TI  - Treatment of hepatitis C by primary care providers.

PMID- 21899462
TI  - BRAF mutations in hairy-cell leukemia.

PMID- 21899463
TI  - BRAF mutations in hairy-cell leukemia.

PMID- 21899465
TI  - Health risks of accidents at nuclear power plants.

PMID- 21899466
TI  - Health risks of accidents at nuclear power plants.

PMID- 21899467
TI  - Health risks of accidents at nuclear power plants.

PMID- 21899468
TI  - Health risks of accidents at nuclear power plants.

PMID- 21899470
TI  - Intravenous thrombolytic therapy for acute ischemic stroke.

PMID- 21899471
TI  - Intravenous thrombolytic therapy for acute ischemic stroke.

PMID- 21899472
TI  - Intravenous thrombolytic therapy for acute ischemic stroke.

PMID- 21899474
TI  - "Bath salts" intoxication.

PMID- 21899476
TI  - The pharmacogenetics of antimalaria artemisinin combination therapy.
AB  - INTRODUCTION: Plasmodium falciparum malaria is one of the world's most lethal
      infectious diseases, commanding millions of drug administrations per year. The
      pharmacogenetics of these drugs is poorly known, although its application can be
      pivotal for the optimized management of this disease. AREAS COVERED: The main
      components of artemisinin combination therapy (ACT), the worldwide main
      antimalarial strategy, are metabolized by the polymorphic CYP3A4 (mefloquine,
      artemether, lumefantrine), CYP2C8 (amodiaquine), CYP2A6 (artesunate) and CYP1A1/2
      (amodiaquine/desethylamodiaquine), with dihydroartemisinin being acted by Phase
      II UDP-glucuronosyltransferases. The worldwide adoption of ACT is leading to a
      large number of antimalarial treatments. Simultaneously, the feared development
      of parasite drug resistance might drive dosing increases. In these scenarios of
      increased drug exposure, pharmacogenetics can be a key tool supporting evidence
      based medicine aiming for the longest possible useful lifespan of this important
      chemotherapy. EXPERT OPINION: Translation in this moment is not operationally
      possible at an individual level, but large population studies are achievable for:
      i) the development of robust pharmacogenetics markers; and ii) the parallel
      development of a pharmacogenetic cartography of malaria settings. Advances in the
      understanding of antimalarial pharmacogenetics are urgent in order to protect the
      exposed populations, enhance the effectiveness of ACT and, consequently,
      contributing for the long aimed elimination of the disease.

PMID- 21899477
TI  - Antithrombotic lipids from Semen Persicae.
AB  - Chemical investigation of Semen Persicae has led to the isolation of decane (1),
      triolein (2), nonacosanoic acid (3), oleic acid ethyl ester (4), palmitic acid
      (5), oleic acid (6) and 15,16-dihydroxy-9Z,12Z-octadecadienoic acid 2,3
      dihydroxypropyl ester (7). Amongst these, compound 7 is a new lipid. Their
      structures were elucidated by chemical and extensive spectral analysis. Their
      anticoagulative activities were also evaluated in vitro, which showed that
      petroleum ether extract and compounds 5-6 could significantly prolong thrombin
      time while methanol extract could obviously inhibit platelet aggregation.

PMID- 21899479
TI  - Mirror agnosia and the mirrored-self misidentification delusion: a hypnotic
      analogue.
AB  - INTRODUCTION: Mirrored-self misidentification is the delusional belief that one's
      reflection in the mirror is a stranger. Current theories suggest that one pathway
      to the delusion is mirror agnosia (a deficit in which patients are unable to use
      mirror knowledge when interacting with mirrors). This study examined whether a
      hypnotic suggestion for mirror agnosia can recreate features of the delusion.
      METHOD: Ten high hypnotisable participants were given either a suggestion to not
      understand mirrors or to see the mirror as a window. Participants were asked to
      look into a mirror and describe what they saw. Participants were tested on their
      understanding of mirrors and received a series of challenges. Participants then
      received a detailed postexperimental inquiry. RESULTS: Three of five participants
      given the suggestion to not understand mirrors reported seeing a stranger and
      maintained this belief when challenged. These participants also showed signs of
      mirror agnosia. No participants given the suggestion to see a window reported
      seeing a stranger. CONCLUSION: Results indicate that a hypnotic suggestion for
      mirror agnosia can be used to recreate the mirrored-self misidentification
      delusion. Factors influencing the effectiveness of hypnotic analogues of
      psychopathology, such as participants' expectations and interpretations, are
      discussed.

PMID- 21899480
TI  - Production of camptothecin by hairy roots and regenerated transformed shoots of
      Ophiorrhiza rugosa var. decumbens.
AB  - Camptothecin (CPT), the derivatives of which are used clinically for the
      treatment of metastatic colon cancer, is isolated from intact plants that can be
      subjected to environmental fluctuations. In vitro cultures may be an alternate
      and continuous source for year-round production of CPT. Since CPT production by
      undifferentiated cell cultures is low, differentiated tissues such as root
      cultures may be a viable alternate source for CPT production. Hairy roots were
      induced in Ophiorriza rugosa, a source of CPT, using Agrobacterium rhizogenes
      strain LBA9402. The hairy roots, when cultured in light, showed spontaneous
      regeneration of shoots. Analysis of CPT levels in the hairy roots and in vitro
      grown transformed shoots revealed 0.009% d.w. and 0.012% d.w., respectively.

PMID- 21899481
TI  - New epothilone congeners from Sorangium cellulosum strain So0157-2.
AB  - As a continuous work to find more epothilone congeners produced by the
      epothilones A and B producing Sorangium cellulosum strain So0157-2 in the large
      scale fermentation (5000 L), we reinvestigated the chemical compositions of the
      fermentation broth. Consequently, two new epothilone variants (1-2) and one new
      natural epothilone derivative (3) were isolated from the fermentation broth.
      Their structures were established as 16-ethyl epothilone B (1), 6-desmethyl-16
      hydroxymethyl epothilone C (2) and 20-ethyl epothilone A (3), respectively, by an
      extensive NMR analysis.

PMID- 21899482
TI  - Two antifungal active triterpenoid saponins from the seeds of Lathyrus plants.
AB  - Two novel triterpenoid glycosides have been isolated from butanolic seeds extract
      of two varieties of Lathyrus plants, i.e. Lathyrus ratan and Lathyrus aphaca.
      Their structures were elucidated as 3-O-[beta-D-glucuronopyranosyl-(1 -> 4)-alpha
      L-arabinopyranosyl-(1 -> 2)-alpha-L-arabinopyranosyl]-olean-11,13(18)-dien-28-oic
      acid (1) and 3-O-{beta-D-xylopyranosyl-(1  ->  2)-beta-D-glcopyranosyl-(1 -> 4)
      [beta-D-glucopyranosyl-(1 -> 2)]-beta-D-xylopyranosyl}-2,16alpha-dihydroxy-4
      hydroxymethyl urs-12-en-28-oic acid (2) on the basis of spectral evidences, i.e.
      FTIR, (1)H-NMR, (13)C-NMR, ESI-MS and FAB-MS data. The isolated saponins were
      tested for their antifungal activity. Compound 1 showed maximum inhibition
      against Colletotrichum dematium (77.8%), whereas compound 2 showed maximum
      inhibition against Alternaria alternata (53.9%).

PMID- 21899483
TI  - YKL-40 protein is a marker of asthma.
AB  - BACKGROUND: Gaining asthma control is still a challenge in a large number of
      patients. It could be facilitated by using biomarkers indicating the grade of
      inflammation and correlating with clinical picture. Chitinases and chitinase-like
      proteins play a role in Th2-type inflammation. Thus, they may be useful in
      diagnosing and monitoring of asthma. OBJECTIVES: The aim of the study was to
      investigate the relevance of YKL-40 as a good biomarker of asthma, its control,
      and severity. METHODS: Level of YKL-40 was determined by means of immunoassay in
      sera of 59 asthmatics (39 women, 20 men, aged 23-76 years) and 29 healthy
      controls (18 women, 11 men, aged 20-80 years). Asthma severity and control were
      assessed according to GINA guidelines. Differences between groups were compared
      with the use of Mann-Whitney's U-test. Correlations between variables were
      assessed with Pearson's test. RESULTS: Symptoms of asthma were found to be
      controlled in 12 (20%), partly controlled in 17 (29%), and uncontrolled in 30
      (51%) patients. YKL-40 levels were significantly higher, on average, in
      asthmatics compared to control group (median levels: 125.3 U and 84.1 U,
      respectively, p < .001). YKL-40 correlated with the number of blood eosinophils
      (r = 0.376, p = 0.05). However, no relations have been found between YKL-40 level
      and asthma severity, control, or total serum IgE (r = -0.05, p = .05).
      CONCLUSION: YKL-40 seems to be a good marker of asthma. However, its level may
      not correlate with clinical outcome.

PMID- 21899484
TI  - Preparation of a polypyrrole-polyvinylsulphonate composite film biosensor for
      determination of phenol based on entrapment of polyphenol oxidase.
AB  - Abstract: In this paper, a novel amperometric phenol biosensor with
      immobilization of polyphenol oxidase (tyrosinase) on electrochemically
      polymerized polypyrrole-polyvinylsulphonate (PPy-PVS) film has been accomplished
      via the entrapment technique on the surface of a platinum electrode. The
      amperometric determination is based on the electrochemical reduction of quinon
      generated in the enzymatic reaction of phenol. The effects of pH and temperature
      were investigated and optimum parameters were found to be 8.0 and 30  degrees C,
      respectively. The linear working range of the electrode was 1.0 * 10(-7) - 5.0 *
      10(-6) M. The storage stability and operation stability of the enzyme electrode
      were also studied.

PMID- 21899485
TI  - Coverage of insulin delivery devices and basal insulin analogs by US managed care
      organizations.
AB  - OBJECTIVE: The perception in the US is that insulin formulations prescribed for
      type 1 and type 2 diabetes and delivered via insulin pens are more costly to
      patients than the same or similar products provided in vials, and that basal
      insulin analogs offered either in pens or vials are likewise more costly to
      patients than human insulin formulations. This study compares levels of coverage
      and copays by private and Medicare Part D plans for insulin pens and vials
      containing basal insulin analogs and for NPH formulations in vials. METHODS: A
      commercially available formulary database (Access Point, Pinsonault Associates;
      updated quarterly) was analyzed as of January 2010 for private insurance plans
      and as of March 2010 for Medicare Part D plans. Analyses were performed for Tier
      level coverage and copays per prescription for basal insulin analogs in pens and
      vials, and NPH in vials. RESULTS: Basal insulin analogs in pens were covered by
      >91% of private and Part D plans. NPH coverage was reported by >92% of private
      plans and 69-95% of Part D plans, depending on brand. Irrespective of delivery
      mode, copays in the majority of private plans for basal insulin analogs and NPH
      were in the >$10-35 range. Copays were higher in Part D plans, with the majority
      of plans and subscribers in a >$35-50 range. Prior authorization was required by
      <10% of insurance plans for insulin analog pen prescriptions, and <3% of plans
      for insulin analog or NPH prescriptions in vials. LIMITATIONS: This analysis was
      descriptive, copay stratification was not based on a statistical model but on
      copay ranges typically used by the plans, and there were no direct correlations
      performed on the numbers of subscribers per plan vs copay or Tier level.
      CONCLUSION: These results counter the widely held perception that insurance
      coverage is less extensive for insulin pens vs vials. Medicare Part D plans often
      had higher copay requirements than private plans for the same product at the same
      copay Tier.

PMID- 21899486
TI  - The impact of rheumatoid arthritis on the burden of disease in urban China.
AB  - OBJECTIVES: The aim of this study is to assess the burden of disease associated
      with the impact of rheumatoid arthritis in urban China. Burden of disease is
      considered from four perspectives: (i) health-related quality-of-life (HRQoL);
      (ii) health status; (iii) employment status; and (iv) absenteeism and
      presenteeism. METHODS: Data are from the 2009 National Health and Wellness Survey
      (NHWS) of urban China. This is an internet-based survey and details the health
      experience of 13,007 respondents. The survey is representative of the urban China
      population at 18 years of age and over (18.1% of the total population). Of those
      responding to the survey, a total of 353 reported that they had been diagnosed
      with rheumatoid arthritis--an unweighted estimate of 2.65%. The sample design
      allows a comparison of those reporting rheumatoid arthritis with those not
      reporting this disease and, hence, a quantitative assessment of the burden of
      disease. Estimates of the quantitative impact of the presence of rheumatoid
      arthritis are through a series of generalized linear regression models. HRQoL is
      evaluated through the SF-12 instrument together with responses to the first item
      of the SF-12, self-reported health status. The SF-12 instrument generates three
      measures of HRQoL: the physical component summary (PCS), the mental component
      summary (MCS) and SF-6D utilities. Health status is captured as a self-report on
      a 5-point scale. Employment status is considered in terms of self-reported labor
      force participation, while absenteeism and presenteeism are estimated from the
      Work Productivity Activity Index (WPAI). Apart from a binary variable capturing
      the presence or absence of rheumatoid arthritis, control variables were included
      to capture the impact of other potential determinants of HRQoL and health status.
      RESULTS: The presence of rheumatoid arthritis in urban China has a significant
      deficit impact on HRQoL as measured by the PCS and MCS components of the SF-12,
      SF-6D absolute utilities and on self-assessed health status. In the case of PCS,
      the deficit impact of rheumatoid arthritis is -2.289 (95%CI: -3.042 to -1.536);
      for MCS -1.472 (95%CI: -2.338 to -0.605) and for utilities -0.025 (95% CI: -0.036
      to -0.014). In the case of health status the odds ratio for the presence of
      rheumatoid arthritis is 1.275 (95%CI 1.031-1.576). The presence of rheumatoid
      arthritis has a marked negative effect, just under 8%, on the likelihood of
      workforce participation. Finally, the presence of rheumatoid arthritis is
      associated with an increased likelihood of absenteeism and presenteeism.
      LIMITATIONS: The NHWS survey has a number of limitations. As the NHWS is an
      internet-based survey, biases may be present due to the lack of internet
      penetration in the urban China population. The extent to which individuals and
      households have internet access is unknown. In addition, the NHWS relies upon
      respondents reporting they have been diagnosed with one or more specific disease
      states. These are not, given the nature of the survey, clinically verified. This
      also introduces a degree of uncertainty. Care should be taken in uncritically
      generalizing these results to the wider China population. CONCLUSIONS: The burden
      of disease associated with self-reported, diagnosed rheumatoid arthritis in urban
      China is substantial. Utilizing a series of multivariate models, substantial
      deficits are associated not only in reported HRQoL and health status but also in
      respect of employment status and, for those in employment, rates of absenteeism
      and presenteeism.

PMID- 21899487
TI  - Adapting the Asthma Life Impact Scale (ALIS) for use in Southern European
      (Italian) and Eastern European (Russian) cultures.
AB  - BACKGROUND: The Asthma Life Impact Scale (ALIS) is a disease-specific measure
      used to assess the quality-of-life of people with asthma. It was developed in the
      UK and US and has proven to be acceptable to patients, to have good psychometric
      properties, and to be unidimensional. OBJECTIVE: This paper reports on the
      adaptation and validation of the ALIS for use in representative Southern European
      (Italian) and Eastern European (Russian) languages. METHODS: The ALIS was
      translated for both cultures using the dual-panel process. The newly translated
      versions were then tested with asthma patients to ensure face and content
      validity. Psychometric properties of the new language versions were assessed via
      a test?re-test postal survey conducted in both countries. LIMITATIONS: It is
      possible that some cultural or language differences still exist between the
      different language versions. Further research should be undertaken to determine
      responsiveness. Further studies designed to determine the clinical validity of
      the Italian ALIS would be valuable. RESULTS: Linguistic nuances were easily
      resolved during the translation process for both language adaptations. Cognitive
      debriefing interviews (Russia n=9, male=11.1%, age mean (SD)=55.4 (13.2); Italy
      n=15, male=66.7%, age mean (SD)=63.5 (11.2)) indicated that the ALIS was easy to
      read and acceptable to patients. Psychometric testing was conducted on the data
      (Russia n=61, age mean (SD)=40.7 (15.4); Italy n=71, male=42.6%, age mean
      (SD)=49.5 (14.1)). The results showed that the new versions of the ALIS were
      consistent (Russian and Italian Cronbach's alpha=0.92) and reproducible (Russian
      test-re-test=0.86; Italian test-re-test=0.94). The Italian adaptation showed the
      expected correlations with the NHP and the Russian adaptation showed strong
      correlations with the CASIS and CAFS and weak-to-moderate correlations with %FEV1
      and %PEF. In both adaptations the ALIS was able to distinguish between
      participants based on self-reported general health, self-reported severity, and
      whether or not they were hospitalized in the previous week.

PMID- 21899488
TI  - "+CLICK": pilot of a web-based training program to enhance ART adherence among
      HIV-positive youth.
AB  - Youth account for almost half of all new HIV infections in the United States.
      Adherence to antiretroviral treatment (ART) is critical for successful
      management, yet reported adherence rates for youth are often low. This study
      pilot-tested "+CLICK," an innovative, web-based, adherence intervention for HIV
      positive youth as an adjunct to traditional clinic-based, self-management
      education. The theory-based application, developed for HIV-infected youth, 13-24
      years of age, provides tailored activities addressing attitudes, knowledge,
      skills, and self-efficacy related to ART adherence. HIV-positive youth (N=10)
      pilot-tested "+CLICK" to assess usability (ease of use, credibility,
      understandability, acceptability, motivation) and short-term psychosocial
      outcomes (importance and self-efficacy related to ART adherence) using a single
      group, pre-/post-test study design in a hospital-based pediatric clinic (n=8) and
      home (n=2) location. Youth were mostly female (80%) and Black (80%). Mean age was
      17.8 years (SD=2.65, range 14-22). All were infected perinatally and had been
      living with HIV all their lives. Most learned their HIV status by age 10 years.
      Sixty percent reported an undetectable viral load, whilst 10% reported a viral
      load of over 50,000. Half (50%) reported a normal CD4 count, whilst 20% reported
      having low CD4 (<200). Usability ratings indicated "+CLICK" was very easy to use
      (70%), trustworthy, and understandable (both>90%). Most (70%) indicated they
      would use "+CLICK" again. Short-term psychosocial outcomes indicate significant
      increase in medication adherence self-efficacy (p<0.05), perceived importance of
      taking antiretroviral medicine close to the right time every day (p<0.05), and
      knowledge about HIV and adherence (p<0.01). Other psychosocial variables and
      behavioral intentions were not significantly impacted. Results suggest that
      "+CLICK" has the potential to affect psychological antecedents to ART adherence.
      Further research on long-term and behavioral effects is indicated prior to
      broader dissemination into clinical practice.

PMID- 21899489
TI  - Developmental changes in the control of saccadic eye movements in response to
      directional eye gaze and arrows.
AB  - We investigated developmental differences in oculomotor control between 10-year
      old children and adults using a central interference task. In this task, the
      colour of a fixation point instructed participants to saccade either to the left
      or to the right. These saccade directions were either congruent or incongruent
      with two types of distractor cue: either the direction of eye gaze of a centrally
      presented schematic face, or the direction of arrows. Children had greater
      difficulties inhibiting the distractor cues than did adults, which revealed
      itself in longer saccade latencies for saccades that were incongruent with the
      distractor cues as well as more errors on these incongruent trials than on
      congruent trials. Counter to our prediction, in terms of saccade latencies, both
      children and adults had greater difficulties inhibiting the arrow than the eye
      gaze distractors.

PMID- 21899490
TI  - Syntheses and evaluation of anti-inflammatory, analgesic and ulcerogenic
      activities of 1,3,4-oxadiazole and 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole
      derivatives.
AB  - Several 2,5-disubstituted-1,3,4-oxadiazoles (4a-f) and 3,6-disubstituted-1,2,4
      triazolo[3,4-b]-1,3,4-thiadiazoles (7a-f) were synthesized and characterized by
      elemental analyses and spectral data. These compounds were screened for their
      anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation activities.
      Compound 7c showed excellent anti-inflammatory and remarkable analgesic activity
      with reduced ulcerogenic and lipid peroxidation activity when compared with
      ibuprofen.

PMID- 21899491
TI  - QSARs on human carbonic anhydrase VA and VB inhibitors of some new not yet
      synthesized, substituted aromatic/heterocyclic sulphonamides as anti-obesity
      agent.
AB  - This paper presents result of quantitative structure-activity relationships
      (QSAR) study realized with the PRECLAV, omega, brood and MOPAC software. The
      dependent property is the inhibitory activity against human carbonic anhydrase
      mitochondrial isoforms VA and VB. The calibration set includes 17
      aromatic/heterocyclic sulphonamides incorporating phenacetyl, pyridylacetyl and
      thienylacetyl tails with three clinically used CA inhibitors namely AZA, TPM and
      ZNS molecules. The prediction set contains 24 others not yet synthesized
      substituted aromatic/heterocyclic sulphonamides having unknown observed values of
      activity. In the presence of prediction set, the predictive quality of QSAR of
      hCA VA (r(2) = 0.9789, F = 418.115, r(2)(CV) = 0.9689) and hCA VB (r(2) = 0.9768;
      F = 379.717; r(2)(CV) = 0.9637) is large. The obtained models suggest a slightly
      different inhibition mechanism for the two isoforms. Large percentage, in weight,
      of CONH molecular fragments seems to be favourable to inhibitory activity of both
      VA and VB.

PMID- 21899492
TI  - Synthesis and cytotoxicity studies of bifunctional hybrids of nitrogen mustards
      with potential enzymes inhibitors based on melamine framework.
AB  - The new class of hybrid anticancer drugs were obtained by selective
      functionalization of the triazine scaffold. These were prepared by rearrangement
      of mono-, bis- and/or tris-(1,3,5-triazin-2-yl)-1,4-diazabicyclo[2.2.2]octanium
      chlorides leading to formation of 2-chloroethylamino fragments attached to 1,3,5
      triazine via one, two or three piperazine rings respectively. Their inhibitory
      effect was found strongly dependent on the structure of substituents in triazine
      ring. The anti-proliferative activity of the hybrids evaluated in vitro by using
      mammalian tumour cells estimated as IC(50) was in the range 0.62-139,78 uM. Both
      cytotoxicity and alkylating activity depended on the substituents of triazine
      ring, however, also the mono-functional analogues of nitrogen mustards, which are
      unable to form liaisons between two DNA strands, induced apoptosis and necrosis
      in the tested cells.

PMID- 21899493
TI  - Structural analysis of structurally diverse alpha-glucosidase inhibitors for
      active site feature analysis.
AB  - In the present investigation, a QSAR analysis on structurally diverse alpha
      glucosidase inhibitors (andrographolide, chromenone, triazole derivatives) was
      performed and the developed models were validated by various validation methods
      (LMO, LOO, LSO, bootstrapping, Y-randomization and test set). The statistical
      parameters calculated for the models show that the developed models are
      statistically significant and have predicted the activities with small residual
      errors. The crossvalidated correlation coefficient (Q(2)) values obtained from
      different validation methods show >0.7 for both the models. Other correlations
      coefficient statistical parameters (R(2)(pred) and R(2)(m)) show that the
      developed models are reliable and robust. The leave-series-out (LSO) results
      reveal that the developed models can predict the activity of new compounds and
      its crossvalidated correlation coefficients' values are comparable with the Q(2)
      values obtained from other validation methods. The descriptors contributed in the
      selected models are suggested that the lower/reduced polarizability on the vdW
      surface area of the molecules and the presence of flexible bonds allow the
      substituents/side chains in the molecules with free movement and with lesser
      stretching energy which are favourable for the alpha-glucosidase inhibitory
      activity. These results reveal that the developed models are statistically
      significant and can be used with other molecular modelling works for designing
      novel alpha-glucosidase inhibitors with multiple activities (HIV, diabetics,
      cancer, etc).

PMID- 21899494
TI  - To mix or not to mix venous blood samples collected in vacuum tubes?
AB  - BACKGROUND: There are recommendations to mix venous blood samples by inverting
      the tubes immediately after venipuncture. Though mixing allows efficient
      anticoagulation in plasma tubes and fast initiation of coagulation in serum
      tubes, the effect on laboratory analyses and risk of haemolysis has not been
      thoroughly evaluated. METHODS: Venous blood samples were collected by
      venipuncture in vacuum tubes from 50 patients (10 or 20 patients in each group).
      Four types of tubes and 18 parameters used in routine clinical chemistry were
      evaluated. For each patient and tube, three types of mixing strategies were used:
      instant mixing, no mixing and 5 min of rest followed by mixing. RESULTS: Most
      analyses did not differ significantly in samples admitted to different mixing
      strategies. Plasma lactate dehydrogenase and haemolysis index showed a small but
      significant increase in samples omitted to instant mixing compared to samples
      without mixing. However, in one out of twenty non-mixed samples, activated
      partial thromboplastin time was seriously affected. CONCLUSIONS: These results
      indicate that mixing blood samples after venipuncture is not mandatory for all
      types of tubes. Instant mixing may introduce interference for those analyses
      susceptible to haemolysis. However, tubes with liquid-based citrate buffer for
      coagulation testing should be mixed to avoid clotting.

PMID- 21899495
TI  - Direct sequencing in cytological specimens as a useful strategy for detecting
      EGFR mutations in non-small cell lung cancer patients.
AB  - BACKGROUND: New therapeutics targeting epidermal growth factor receptor (EGFR)
      have significantly improved tumor responses to therapy in non-small cell lung
      cancer (NSCLC) patients. Molecular testing for EGFR mutations informs important
      therapeutic decisions in clinical practice. In this study, we sought to validate
      the clinical relevance of sequencing-based EGFR mutation testing combined with
      cytological analysis using body fluid specimens. METHODS: Two NSCLC cell lines
      were used in sensitivity analyses. In addition, we performed cytological analyses
      and directly sequencing of exons 18-21, for 32 specimens. The absence of EGFR
      mutations determined by direct sequencing in 14 specimens was confirmed by real
      time PCR. Changes made to patients' therapeutic strategies after reports of EGFR
      mutation status were investigated by querying electronic medical records.
      RESULTS: Sensitivity studies showed that detection of in-frame deletions in exon
      19 and point mutations in exon 21 was possible in specimens containing 10% and 5%
      mutant DNA, respectively. In clinical practice, EGFR mutations were detected in
      18 of 32 specimens (56.3%). Twelve patients with EGFR mutations detected by
      direct sequencing were started on treatment with EGFR tyrosine kinase inhibitor
      (TKI) after reports of EGFR mutation. EGFR-TKI therapy was discontinued for two
      patients with TKI-resistant T790M mutation. The results of real-time PCR were
      consistent with those of direct sequencing in 13 of 14 specimens (92.9%) in which
      no mutation was detected by direct sequencing. CONCLUSIONS: Combined direct
      sequencing and cytological analysis of body fluid specimen might be clinically
      useful and sensitive test for the detection of EGFR mutations in NSCLC patients.

PMID- 21899496
TI  - Heterophilic antibody interference in commercial immunoassays; a screening study
      using paired native and pre-blocked sera.
AB  - BACKGROUND: Heterophilic antibodies are still an important source of interference
      in immunoassays. We have conducted a screening study for interference in a panel
      of commercially available assays using two sera known to contain high titer Fc
      reactive heterophilic antibodies. METHODS: The sera were distributed to
      laboratories participating in the Nordic External Quality Assessment cooperation
      (EQANord). Duplicate samples pre-blocked with aggregated murine monoclonal MAK33
      were also supplied. Discrepancies (>50%) between the results for native and
      blocked samples were used to classify the tested assays as susceptible to
      interference. A total of 170 different assay kits covering 91 analytes were
      tested. RESULTS: We found that 21 assays, covering 19 different analytes, were
      susceptible to interference from the heterophilic antibodies in the two sera.
      Many of these are clinically and commercially important assays. Some of the false
      results were grossly elevated and could have been detrimental to patient care in
      a clinical setting. CONCLUSIONS: Heterophilic antibodies with Fc-reactivity
      remain a threat. A more widespread use of antibody fragments and aggregated
      immunoglobulin could potentially improve the heterophilic antibody resistance of
      assays intended for clinical use.

PMID- 21899498
TI  - Solid-phase microextraction: a multi-purpose microtechnique.

PMID- 21899500
TI  - Bioanalysis: challenges and solutions seminar.
AB  - Industry challenges and solutions for bioanalysis were top of the agenda for the
      Spring Seminar organized by Quotient Bioresearch in Munich, Germany. The seminar
      was attended by representatives from pharmaceutical and biotechnology
      organisations across Europe and featured debates and panel discussions from
      leading industry speakers on new techniques and hot topics, including the latest
      industry guidelines.

PMID- 21899501
TI  - Quantitation of locked nucleic acid antisense oligonucleotides in mouse tissue
      using a liquid-liquid extraction LC-MS/MS analytical approach.
AB  - BACKGROUND: A significant challenge of oligonucleotide bioanalysis is the
      selective extraction from complex tissue samples, where the molecules that
      distribute into the intracellular space are extensively protein bound and sit
      amongst a high concentration of endogenous nucleic acid material. Published
      analytical methodology currently purports extensive sample preparation
      requirements that include cell lysis steps, homogenization and dual cleanup with
      liquid-liquid extraction and solid-phase extraction, prior to injection. RESULTS:
      We have developed a simple liquid-liquid extraction approach to rapidly isolate
      antisense oligonucleotides from biological tissues with high recovery and
      combined these preparative steps with a robust monolithic column LC-MS/MS setup.
      The platform showed improved chromatographic resolution and detection sensitivity
      over standard reversed-phase columns and required a low sample volume.
      CONCLUSION: The high-throughput method was sufficient to accurately quantify
      multiple antisense oligonucleotides in mouse tissue and plasma down to low ng/g
      and ng/ml levels, respectively, for pharmacokinetic determination, and exhibited
      a high degree of specificity.

PMID- 21899502
TI  - Evaluation of homogenization techniques for the preparation of mouse tissue
      samples to support drug discovery.
AB  - BACKGROUND: In early drug-discovery research, understanding the tissue
      distribution of drug at the site of action can help to predict the toxicity,
      efficacy and exposure level of the drug. The bottleneck of tissue analysis by LC
      MS/MS is the time-consuming homogenization step. RESULTS: Both mechanical and
      enzymatic techniques for mouse tissue homogenization were evaluated, which
      included bead beater, polytron and enzymatic digestion. Brain, bone marrow,
      kidney, spleen and liver tissues can be homogenized effectively using the bead
      beater alone. Lung and heart tissues were best treated with collagenase first and
      then homogenized by the bead beater. CONCLUSION: Homogenization conditions for
      seven mouse tissues have been evaluated and optimized. These findings will
      expedite the preparation of tissue samples for analysis.

PMID- 21899503
TI  - Large-volume injection of sample diluents not miscible with the mobile phase as
      an alternative approach in sample preparation for bioanalysis: an application for
      fenspiride bioequivalence.
AB  - BACKGROUND: Liquid-liquid extraction of target compounds from biological matrices
      followed by the injection of a large volume from the organic layer into the
      chromatographic column operated under reversed-phase (RP) conditions would
      successfully combine the selectivity and the straightforward character of the
      procedure in order to enhance sensitivity, compared with the usual approach of
      involving solvent evaporation and residue re-dissolution. Large-volume injection
      of samples in diluents that are not miscible with the mobile phase was recently
      introduced in chromatographic practice. The risk of random errors produced during
      the manipulation of samples is also substantially reduced. RESULTS: A
      bioanalytical method designed for the bioequivalence of fenspiride containing
      pharmaceutical formulations was based on a sample preparation procedure involving
      extraction of the target analyte and the internal standard (trimetazidine) from
      alkalinized plasma samples in 1-octanol. A volume of 75 ul from the octanol layer
      was directly injected on a Zorbax SB C18 Rapid Resolution, 50 mm length * 4.6 mm
      internal diameter * 1.8 um particle size column, with the RP separation being
      carried out under gradient elution conditions. Detection was made through
      positive ESI and MS/MS. Aspects related to method development and validation are
      discussed. CONCLUSIONS: The bioanalytical method was successfully applied to
      assess bioequivalence of a modified release pharmaceutical formulation containing
      80 mg fenspiride hydrochloride during two different studies carried out as single
      dose administration under fasting and fed conditions (four arms), and multiple
      doses administration, respectively. The quality attributes assigned to the
      bioanalytical method, as resulting from its application to the bioequivalence
      studies, are highlighted and fully demonstrate that sample preparation based on
      large-volume injection of immiscible diluents has an increased potential for
      application in bioanalysis.

PMID- 21899504
TI  - Quantitative determination of free and total dopamine in human plasma by LC
      MS/MS: the importance of sample preparation.
AB  - BACKGROUND: Two methods have been developed and validated for the determination
      of free and total dopamine in human plasma. They are based on solid-phase
      extraction of the analyte from the matrix by covalent complexation with
      phenylboronic acid, followed by derivatization with ethylchloroformate. The
      derivative is quantified by reversed-phase liquid chromatography on a C18 column
      and positive electrospray ionization MS/MS. RESULTS: The high selectivity
      obtained, in combination with the stable and relatively non-polar nature of the
      derivatized analyte, enables the reliable quantification of dopamine in the range
      0.05 to 20 ng/ml in a 5 min run time, using only 100 ul of sample. Total dopamine
      concentrations are determined (range 1 to 400 ng/ml) by including an acidic
      hydrolysis step, which converts the sulphate and glucuronide conjugates to free
      dopamine prior to extraction. The method was applied to quantify free and total
      dopamine levels in human plasma after dosing with the anti-Parkinson's drug
      combination L-dopa/carbidopa with and without entacapone. CONCLUSION: A sensitive
      and selective LC-MS/MS method has been developed and validated for the
      determination of free and total dopamine in human plasma. This article
      demonstrates how essential careful optimization of the sample preparation
      procedures was for developing a successful method.

PMID- 21899505
TI  - Direct injection of lipophilic compounds in the organic phase from liquid-liquid
      extracted plasma samples onto a reversed-phase column.
AB  - BACKGROUND: A high-throughput bioanalytical methodology for analysis and
      quantification of lipophilic pharmaceutical compounds in plasma using liquid
      liquid extraction (LLE) was developed. RESULTS: A fast and robust alternative to
      the widely used protein precipitation of plasma samples is sometimes required in
      order to avoid matrix effects in MS detection. LLE is known to produce clean
      extracts and hence reduce levels of matrix components that cause ion suppression.
      The proposed sample preparation was automated LLE using 96-well plates and a
      Tecan GenMate 96-tips liquid handling robot. With direct injection of the organic
      phase (methyl tert-butyl ether: iso-hexane 50:50 v/v) onto a reversed-phase
      column and without evaporation of the organic phase and reconstitution of the
      sample, the LLE was no more time consuming than standard protein precipitation,
      furthermore, matrix effects were minimized. The small injection volume (5 ul)
      when used with lipophilic compounds and a rapid gradient elution made it possible
      to inject the organic phase with maintained chromatographic performance. Good
      chromatographic behavior was confirmed for eight commercially available
      lipophilic compounds. CONCLUSIONS: The proposed method of LLE with injection of
      the organic phase onto a reversed-phase column in LC-MS/MS is no more time
      consuming than standard protein precipitation, and matrix effects were minimized,
      thus making it suitable as a high-throughput bioanalytical methodology for use in
      drug discovery.

PMID- 21899506
TI  - An automation-assisted generic approach for biological sample preparation and LC
      MS/MS method validation.
AB  - BACKGROUND: Although it is well known that automation can provide significant
      improvement in the efficiency of biological sample preparation in quantitative LC
      MS/MS analysis, it has not been widely implemented in bioanalytical laboratories
      throughout the industry. This can be attributed to the lack of a sound strategy
      and practical procedures in working with robotic liquid-handling systems.
      RESULTS: Several comprehensive automation assisted procedures for biological
      sample preparation and method validation were developed and qualified using two
      types of Hamilton Microlab liquid-handling robots. The procedures developed were
      generic, user-friendly and covered the majority of steps involved in routine
      sample preparation and method validation. CONCLUSION: Generic automation
      procedures were established as a practical approach to widely implement
      automation into the routine bioanalysis of samples in support of drug-development
      programs.

PMID- 21899507
TI  - Overview of extraction methods for analysis of vitamin D and its metabolites in
      biological samples.
AB  - In the last decade the scientific and medical community was confronted with a
      renewed interest in vitamin D and its metabolites, interest prompted by new
      discoveries regarding the association between members of the vitamin D family and
      a great number of physiological functions and pathological states. An impressive
      number of research projects have helped clear the path towards a better
      understanding of the functions of vitamin D and have resulted in the development
      of numerous methods of analysis. This review focuses on the various extraction
      methods used for analysis of vitamin D in research or clinical settings. Two main
      extractive methods are usually employed: liquid-liquid extraction and solid-phase
      extraction. Some methods use no extraction step and direct analysis is performed
      at the cost of significantly increased matrix interference. On the other hand,
      other methods use combined extraction techniques, and even additional
      derivatization steps in order to increase the sensitivity and accuracy of the
      analysis. The method of choice ultimately depends on the research question and
      the purpose of the study.

PMID- 21899508
TI  - Sample treatment based on extraction techniques in biological matrices.
AB  - The importance of sample preparation methods as the first stage in bioanalysis is
      described. In this article, the sample preparation concept and strategies will be
      discussed, along with the requirements for good sample preparation. The most
      widely used sample preparation methods in the pharmaceutical industry are
      presented; for example, the need for same-day rotation of results from large
      numbers of biological samples in pharmaceutical industry makes high throughput
      bioanalysis more essential. In this article, high-throughput sample preparation
      techniques are presented; examples are given of the extraction and concentration
      of analytes from biological matrices, including protein precipitation, solid
      phase extraction, liquid-liquid extraction and microextraction-related
      techniques. Finally, the potential role of selective extraction methods,
      including molecular imprinted phases, is considered.

PMID- 21899509
TI  - Novel strategies for sample preparation in forensic toxicology.
AB  - This paper provides a review of novel strategies for sample preparation in
      forensic toxicology. The review initially outlines the principle of each
      technique, followed by sections addressing each class of abused drugs separately.
      The novel strategies currently reviewed focus on the preparation of various
      biological samples for the subsequent determination of opiates, benzodiazepines,
      amphetamines, cocaine, hallucinogens, tricyclic antidepressants, antipsychotics
      and cannabinoids. According to our experience, these analytes are the most
      frequently responsible for intoxications in Greece. The applications of
      techniques such as disposable pipette extraction, microextraction by packed
      sorbent, matrix solid-phase dispersion, solid-phase microextraction, polymer
      monolith microextraction, stir bar sorptive extraction and others, which are
      rapidly gaining acceptance in the field of toxicology, are currently reviewed.

PMID- 21899511
TI  - PD-1 and autoimmunity.
AB  - An initiating T cell response requires both costimulatory signaling and T cell
      receptor/MHC binding. The immune system balances positive and negative
      costimulatory signal pathways to activate and deactivate T cells. This review
      focuses primarily on PD-1 and its ligands, which form a crucial inhibitory
      costimulatory pathway for maintaining peripheral tolerance, and their
      contribution to autoimmunity. Since 1992, when PD-1 was isolated, many studies
      have described the physiological roles of PD-1 signaling, reported relationships
      between Pdcd-1 gene polymorphism and autoimmune diseases, and applied PD-1/PD-1
      ligand modulation to clinical trials. This review summarizes recent advances and
      future therapeutic applications of PD-1 and its ligands to autoimmune diseases.

PMID- 21899512
TI  - Intracellular pattern recognition receptors and renal ischemia.
AB  - Renal ischemia is a common cause of acute kidney injury in hospitalized patients.
      In certain settings renal ischemia is unavoidable, such as in kidneys harvested
      for transplantation. The molecular and cellular mechanisms that lead to the
      syndrome of ischemic renal injury are complicated and involve multiple cell types
      within the kidney, including renal epithelium and vasculature. Although it has
      been difficult to define pharmacologic targets for AKI, emerging information
      about a newly discovered host defense system is providing hope for novel
      pharmacologic targets to prevent and treat AKI. Molecular initiators of damage
      associated with hypoxia involve a phylogenically conserved host defense system
      called the innate immune system. Data point to an essential role for receptors of
      the innate immune system, particularly the membrane-bound Toll-like receptors and
      the intracellular nucleotide-binding oligomerization domain-like receptors. These
      receptors have been identified in human and rodent kidneys, and many
      investigators have shown that their deletion protects from experimental
      ischemia/reperfusion injury (a model for ischemic acute kidney injury). This
      review details current information about the innate immune system and the
      ischemic kidney with a focus on the emerging role of intracellular innate immune
      receptors.

PMID- 21899513
TI  - Mechanisms behind the anti-inflammatory actions of insulin.
AB  - The epidemic of diabetes mellitus is worsening worldwide. Diabetes mellitus is a
      chronic metabolic disease characterized by inappropriate recurrent or persistent
      hyperglycemia. Numerous studies have demonstrated that hyperglycemia, the most
      significant predictor of poor clinical outcome in diabetes mellitus patients, can
      directly promote an inflammatory response and oxidative stress. Although there
      are various causes of DM, all eventually lead to absolute or relative insulin
      deficiency and death of pancreatic beta-cells. Thus, insulin inevitably becomes
      the primary medication used to treat the disease and prevent diabetic
      complications in all DM patients. Interestingly, an emerging body of evidence
      suggests that insulin suppresses the inflammatory process, not only through
      preventing hyperglycemia but also by modulating key inflammatory molecules. In
      this review, we discuss the findings of studies done in vitro as well as clinical
      trials that have demonstrated an anti-inflammatory action of insulin and that
      have pointed to mechanisms responsible for this effect. Further, we discuss how
      the anti-inflammatory action of insulin bears on our current understanding of the
      pathophysiology and complications of both type 1 and type 2 diabetes.

PMID- 21899514
TI  - Chemokines in respiratory viral infections: focus on their diagnostic and
      therapeutic potential.
AB  - Chemokines are small chemoattractant cytokines involved in cell trafficking and
      activation. Despite the general nonspecific nature of chemokine activity in
      certain instances, specific chemokine expression patterns have been associated
      with specific disease states. In the field of respiratory viral infection,
      evidence suggests that response to viral invasion is regulated by a distinct
      chemokine expression profile involving more CC chemokines than CXC chemokines.
      Moreover, among the CC chemokines, CCL3 and CCL5 appear to be most commonly
      implicated in viral respiratory disease. Most data available in this field have
      been derived from in vitro studies, as well as studies conducted in animal models
      with limited evidence obtained in settings of actual human disease. In the
      present review, we focus on the diagnostic, prognostic, and therapeutic potential
      of virus-induced chemokine activity as reflected by studies conducted in actual
      disease states, either in animal models or humans. We further discuss whether
      these data advocate chemokines as a realistic clinical tool for the management of
      viral infection.

PMID- 21899515
TI  - Ectopic study of calcium phosphate cement seeded with pBMP-2 modified canine
      bMSCs mediated by a non-viral PEI derivative.
AB  - We have evaluated the ectopic new bone formation effects of CPC (calcium
      phosphate cement) seeded with pBMP-2 (plasmids containing bone morphogenetic
      protein-2 gene) transfected canine bMSCs (bone marrow stromal cells) mediated by
      a non-viral PEI (polyethylenimine) derivative (GenEscortTM II) in nude mice.
      Canine bMSCs were transfected with pBMP-2 or pEGFP (plasmids containing enhanced
      green fluorescent protein gene) mediated by GenEscortTM II in vitro, and the
      osteoblastic differentiation was explored by ALP (alkaline phosphatase) staining,
      ARS (alizarin red S) staining and RT-qPCR (real-time quantitative PCR) analysis.
      Ectopic bone formation effects of CPC/pBMP-2 transfected bMSCs were evaluated and
      compared with CPC/pEGFP transfected bMSCs or CPC/untransfected bMSCs through
      histological, histomorphological and immunohistochemical analysis 8 and 12 weeks
      post-operation in nude mice. Transfection efficiency was up ~35% as demonstrated
      by EGFP (enhanced green fluorescent protein) expression. ALP and ARS staining
      were stronger with pBMP-2 gene transfection, and mRNA expression of BMP-2 (bone
      morphogenetic protein-2), Col 1 (collagen 1) and OCN (osteocalcin) in pBMP-2
      group was significantly up-regulated at 6 and 9 days. Significantly higher NBV
      (new bone volume) was achieved in pBMP-2 group than in the control groups at 8
      and 12 weeks (P<0.05). In addition, immunohistochemical analysis indicated higher
      OCN expression in pBMP-2 group (P<0.01). We conclude that CPC seeded with pBMP-2
      transfected bMSCs mediated by GenEscortTM II could enhance ectopic new bone
      formation in nude mice, suggesting that GenEscortTM II mediated pBMP-2 gene
      transfer is an effective non-viral method and CPC is a suitable scaffold for gene
      enhanced bone tissue engineering.

PMID- 21899516
TI  - Relaxin-like factor (RLF)/insulin-like peptide 3 (INSL3) is secreted from
      testicular Leydig cells as a monomeric protein comprising three domains B-C-A
      with full biological activity in boars.
AB  - RLF (relaxin-like factor), also known as INSL3 (insulin-like peptide 3), is a
      novel member of the relaxin/insulin gene family that is expressed in testicular
      Leydig cells. Despite the implicated role of RLF/INSL3 in testis development, its
      native conformation remains unknown. In the present paper we demonstrate for the
      first time that boar testicular RLF/INSL3 is isolated as a monomeric structure
      with full biological activity. Using a series of chromatography steps, the native
      RLF/INSL3 was highly purified as a single peak in reverse-phase HPLC. MS/MS
      (tandem MS) analysis of the trypsinized sample provided 66% sequence coverage and
      revealed a distinct monomeric structure consisting of the B-, C- and A-domains
      deduced previously from the RLF/INSL3 cDNA. Moreover, the N-terminal peptide was
      four amino acid residues longer than predicted previously. MS analysis of the
      intact molecule and PMF (peptide mass fingerprinting) analysis at 100% sequence
      coverage confirmed this structure and indicated the existence of three site
      specific disulfide bonds. RLF/INSL3 retained full bioactivity in HEK (human
      embryonic kidney)-293 cells expressing RXFP2 (relaxin/insulin-like family peptide
      receptor 2), the receptor for RLF/INSL3. Furthermore, RLF/INSL3 was found to be
      secreted from Leydig cells into testicular venous blood. Collectively, these
      results indicate that boar RLF/INSL3 is secreted from testicular Leydig cells as
      a B-C-A monomeric structure with full biological activity.

PMID- 21899517
TI  - The Golgi apparatus in the endomembrane-rich gastric parietal cells exist as
      functional stable mini-stacks dispersed throughout the cytoplasm.
AB  - BACKGROUND INFORMATION: Acid-secreting gastric parietal cells are polarized
      epithelial cells that harbour highly abundant and specialized, H+,K+ ATPase
      containing, tubulovesicular membranes in the apical cytoplasm. The Golgi
      apparatus has been implicated in the biogenesis of the tubulovesicular membranes;
      however, an unanswered question is how a typical Golgi organization could
      regulate normal membrane transport within the membrane-dense cytoplasm of
      parietal cells. RESULTS: Here, we demonstrate that the Golgi apparatus of
      parietal cells is not the typical juxta-nuclear ribbon of stacks, but rather
      individual Golgi units are scattered throughout the cytoplasm. The Golgi membrane
      structures labelled with markers of both cis- and trans-Golgi membrane,
      indicating the presence of intact Golgi stacks. The parietal cell Golgi stacks
      were closely aligned with the microtubule network and were shown to participate
      in both anterograde and retrograde transport pathways. Dispersed Golgi stacks
      were also observed in parietal cells from H+,K+ ATPase-deficient mice that lack
      tubulovesicular membranes. CONCLUSIONS: These results indicate that the unusual
      organization of individual Golgi stacks dispersed throughout the cytoplasm of
      these terminally differentiated cells is likely to be a developmentally regulated
      event.

PMID- 21899518
TI  - Respiration characteristics of mitochondria in parental and giant transformed
      cells of the murine Nemeth-Kellner lymphoma.
AB  - Respiration characteristics of mitochondria of the parental and giant cells of
      murine NK/Ly (Nemeth-Kellner lymphoma) were studied. The giant cell-enriched
      ascites were obtained by serial intraperitoneal injections of vinblastine in
      tumour-bearing mice. Ascites containing >70% giant cells were used. Their
      diameter of was over 17 MUm (~2800 MUm(3)), while the diameter of the parental
      cells was 12.7 MUm (1100 MUm(3)). The respiration rate of mitochondria in situ
      was measured by oxygen consumption in intact and digitonin-permeabilized NK/Ly
      cells. Endogenous respiration of intact giant NK/Ly cells was three times higher
      compared to the parental ones, roughly in agreement with the volume change. The
      giant NK/Ly cells were far more resistant to permeabilization with digitonin than
      the parental cells, as shown by Trypan Blue and LDH (lactate dehydrogenase)
      release tests. After digitonin permeabilization, oxygen consumption was reduced
      to a minimal level (0.06 ng atom O/(s * 106 cells) in both types of cells.
      Addition of alpha-ketoglutarate or succinate to the incubation medium increased
      oxygen consumption in the parental cells by 46 and 164% respectively. In the
      giant NK/Ly cells, the corresponding increases were 164 and 276%. Addition of ADP
      to alpha-ketoglutarate- or succinate-supplemented medium further stimulated
      oxygen consumption of the permeabilized NK/Ly cells; however, the effect of ADP
      was more pronounced in the giant cells. In addition, indices of respiratory
      control were significantly higher in the giant cells. Oligomycin suppressed
      considerably the respiration of the intact giant cells but had a much weaker
      effect on parental cells. Thus, giant NK/Ly cells possess much higher respiration
      rates and show tighter coupling between the respiration and oxidative
      phosphorylation compared with parental cells.

PMID- 21899519
TI  - B*13:50, a novel HLA-B*13 allele, identified by sequence-based typing.
AB  - We report a novel HLA-B*13 allele, B*13:50, found using high-resolution sequence
      based typing in a Chinese donor. B*13:50 differs from B*13:01:01 by a single
      nucleotide substitution (A->T) at position 482, in exon 3.

PMID- 21899520
TI  - Coming of age in Spain: the self-identification, beliefs and self-esteem of the
      second generation.
AB  - We review the literature on determinants of ethnic/national self-identities and
      self-esteem as a prelude to examining these outcomes among a large, statistically
      representative sample of second generation adolescents in Madrid and Barcelona.
      While these psycho-social outcomes are malleable, they still represent important
      dimensions of immigrant adaptation and can have significant consequences both for
      individual mobility and collective mobilizations. Current theories are largely
      based on data from the USA and other Anglophone countries. The availability of a
      new large Spanish survey allows us to test those theories in an entirely
      different socio-cultural context. The analysis concludes with a structural
      equations model that summarizes key determinants of national identities and self
      esteem among children of immigrants in Spain. Theoretical and practical
      implications of these findings are discussed.

PMID- 21899521
TI  - Telling a modest story: accounts of men's upward mobility from the National Child
      Development Study.
AB  - While the pattern of social mobility in postwar Britain has been extensively
      studied, revealing considerable upward mobility, much less is known about the
      subjective dimension to mobility. In this article, we employ a new sample of in
      depth interviews with 50-year old men from the National Child Development Study
      to examine in detail the link between objective mobility patterns and the way the
      upwardly mobile narrate their life trajectories. In contrast to the mobility
      ideology suggested by the Oxford mobility survey of the early 1970s, in which the
      upwardly mobile recognized and internalized their success as a project of the
      self, we report how members of this later generation of men with highly
      successful careers prefer instead to articulate 'modest' life stories. By
      treating the career as a narrative device, we are able to show how the disavowal
      of the dominant, linear hierarchical career model by these men allows them to
      tell particular and distinctive stories which establish their individuality and
      personhood, while, paradoxically, recognizing the cultural power of the dominant
      model. In particular, we highlight the use of 'linear contingent' narratives by
      these men, in which specific events, especially those connected with occupational
      and geographical transitions, are deployed as contingent thresholds to mark out
      key shifts and passages in their lives. We then compare their accounts with those
      of immobile and downwardly men, who instead deploy 'ghostly' stories, preoccupied
      by the past, or defensive accounts, displaying unease with their failure to live
      up to the expectations of the linear career model. Having shown that men's
      accounts of mobility are suffused with an awareness of their need to establish
      their own individuality through repudiating the social trope of the instrumental
      careerist, we conclude that the links between career identities and objective
      mobility patterns are not straightforward and need careful unravelling.

PMID- 21899522
TI  - Homeless identities: enacted and ascribed.
AB  - Homelessness has been a perennial concern for sociologists. It is a confronting
      phenomenon that can challenge western notions of home, a discrete family unit and
      the ascetics and order of public space. To be without a home and to reside in
      public places illustrates both an intriguing way of living and some fundamental
      inadequacies in the functioning of society. Much homelessness research has had
      the consequence of isolating the 'homeless person' as distinct category or indeed
      type of individual. They are ascribed with homeless identities. The homeless
      identity is not simply presented as one dimensional and defining, but this
      imposed and ill-fitting identity is rarely informed by a close and long-term
      engagement with the individuals it is supposed to say something about. Drawing on
      a recent Australian ethnographic study with people literally without shelter,
      this article aims to contribute to understandings of people who are homeless by
      outlining some nuanced and diverse aspects of their identities. It argues that
      people can and do express agency in the way they enact elements of the self, and
      the experience of homelessness is simultaneously important and unimportant to
      understand this. Further, the article suggests that what is presumably known
      about the homeless identity is influenced by day-to-day lives that are on public
      display.

PMID- 21899523
TI  - 'Being there': multidimensionality, reflexivity and the study of emotional lives.
AB  - Emotional lives tend to be untidy. Yet despite a growing recognition of this,
      sociological research designs rarely mirror the multidimensionality they are
      striving to represent. This article takes as its starting point a recent study of
      beliefs and practices about emotional support and emotions talk in Britain, to
      illustrate how a methodologically mixed approach offers particular purchase on
      what passes between us in our everyday emotional lives and in research about
      these lives. The notion of 'being there' is drawn on to help make this argument.
      Moving between 'being there' as topic, a form of emotional support, and 'being
      there' as a methodological resource, the article concludes that the analytical
      claims we make about our emotional lives are strengthened through a
      methodologically mixed - and by necessity, reflexive - approach which explores,
      rather than smooths out, the ragged, sometimes indeterminate, edges between
      methods.

PMID- 21899524
TI  - Rational choice and the political bases of changing Israeli counterinsurgency
      strategy.
AB  - Israeli counterinsurgency doctrine holds that the persistent use of credible
      threat and disproportionate military force results in repeated victories that
      eventually teach the enemy the futility of aggression. The doctrine thus endorses
      classical rational choice theory's claim that narrow cost-benefit calculations
      shape fixed action rationales. This paper assesses whether Israel's strategic
      practice reflects its counterinsurgency doctrine by exploring the historical
      record and the association between Israeli and Palestinian deaths due to low
      intensity warfare. In contrast to the expectations of classical rational choice
      theory, the evidence suggests that institutional, cultural and historical forces
      routinely override simple cost-benefit calculations. Changing domestic and
      international circumstances periodically cause revisions in counterinsurgency
      strategy. Credible threat and disproportionate military force lack the predicted
      long-term effect.

PMID- 21899525
TI  - Hazards of neoliberalism: delayed electric power restoration after Hurricane Ike.
AB  - This case study explores how neoliberal policies shape the impacts of a natural
      disaster. We investigate the reactions to major damages to the electric power
      system and the restoration of power in the wake of Hurricane Ike, which
      devastated the Houston, Texas, metropolitan area in September 2008. We argue that
      the neoliberal policy agenda insured a minimalist approach to the crisis and
      generated dissatisfaction among many residents. The short-term profitability
      imperative shifted reconstruction costs to consumers, and prevented efforts to
      upgrade the electric power infrastructure to prepare for future disasters. We
      illustrate the serious obstacles for disaster mitigation and recovery posed by
      neoliberal policies that privatize public goods and socialize private costs.
      Neoliberalism neither addresses the needs of a highly stratified public nor their
      long-term interests and safety.

PMID- 21899526
TI  - Tightening the focus: moral panic, moral regulation and liberal government.
AB  - The purpose of this article is to tighten the focus of moral panic studies by
      clarifying and elaborating on an analytical framework that conceptualizes moral
      panic as a form of moral regulation. The first part of the article explains why
      moral panic should be conceptualized as a form of moral regulation. The second
      part presents a rejoinder to Critcher's (2009) critique of the widening focus of
      moral panic studies. The third part elaborates on the conceptual relationship
      between the sociologies of moral panic and moral regulation by offering fresh
      insights into the sociological and political importance of moral panic as a
      technique of liberal government.

PMID- 21899527
TI  - Review essay: empires, ancient and modern.
AB  - This essay drews attention to two books on empires by historians which deserve
      the attention of sociologists. Bang's model of the workings of the Roman economy
      powerfully demonstrates the tributary nature of per-industrial tributary empires.
      Darwin's analysis concentrates on modern overseas empires, wholly different in
      character as they involved the transportation of consumption items for the many
      rather than luxury goods for the few. Darwin is especially good at describing the
      conditions of existence of late nineteenth century empires, noting that their
      demise was caused most of all by the failure of balance of power politics in
      Europe. Concluding thoughts are offered about the USA.

PMID- 21899530
TI  - Different transcriptional ratios of male and female transmitted mitochondrial DNA
      and tissue-specific expression patterns in the blue mussel, Mytilus
      galloprovincialis.
AB  - In some bivalve species, paternal mitochondrial DNA (mtDNA) from sperm is
      transmitted to the offspring. This is called "doubly uniparental inheritance"
      (DUI). Under DUI, male offspring receive both paternal (M type) and maternal (F
      type) mtDNA. Females predominantly receive F type. Expression levels of M and F
      type mtDNA and mitochondrial RNA localization have not been studied extensively.
      In this study, we quantified M and F type mtDNA and their expression levels in
      male and female somatic tissues and gonads with real-time polymerase chain
      reaction (PCR) in the blue mussel, Mytilus galloprovincialis. M and F type
      expression patterns were studied with in situ hybridization, using probes
      specific to M and F type mtDNA in the cytochrome b region. We found that (i) F
      type mtDNA was expressed in somatic tissues and female gonads, while M type was
      not expressed in these tissues; (ii) M type expression in male gonads was
      limited, but strong expression was observed during early spermatogenesis; and
      (iii) F type expression ratios were significantly lower in female gonads than in
      somatic tissues and lower than both M and F type expression ratios in male
      gonads. We propose (i) different systems for M and F type tissue-specific
      transcriptional regulation; and (ii) different functions for F and M type mtDNA,
      with F type being functional in somatic tissues and female gonads and M type
      functioning only in spermatogenetic cells.

PMID- 21899531
TI  - Norrin immunolocalization and its possible functions in rat endometrium during
      the estrus cycle and early pregnancy.
AB  - Mutations in Norrie Disease Pseudoglioma (NDP) gene cause serious sight loss,
      deafness and mental retardation in Norrie disease patients via the impairment of
      angiogenesis. Since norrin is a Wnt pathway ligand, it could function in several
      tissues other than eye and nervous systems. Therefore, the aim of the present
      study was to determine the possible function of norrin in angiogenesis, cellular
      differentiation in stroma and in decidua and the survival of those cells using
      immunofluorescent labeling. While norrin had a uniform distribution in stroma and
      in blood vessels, it had a strong expression in luminal and glandular epithelia
      during the estrus cycle. Norrin had strong immunolocalization in the
      antimesometrial decidual reaction zone on day 7 of gestation, whereas it had a
      decreased expression in the mesometrial uterine luminal epithelium along with an
      increased localization in blood vessels and decidual cells of the same region on
      day 8 of gestation. As from day 9 of gestation, norrin demonstrated rather strong
      expression in the decidual cells and blood vessels of the mesometrial region in
      which the chorioallantoic placenta was going to develop. In all periods studied,
      norrin had rather weak expression in the primary decidual zone surrounding the
      embryo. Findings of the present study suggested that norrin might regulate the
      decidual reaction and the placental angiogenesis along with the survival and the
      differentiation of luminal and glandular epithelial and decidual cells in rats.
      In addition, it could play indirect important roles in the control of
      trophoblastic invasion and the programmed cell death.

PMID- 21899532
TI  - Radiofrequency lesioning for epileptogenic periventricular nodular heterotopia: a
      rational approach.
AB  - Periventricular nodular heterotopias (PNHs) are frequently associated with
      pharmacoresistant epilepsy. They are considered part of a dysfunctional network,
      connected to the overlying cortex. Therefore, removal of the PNHs and additional
      cortectomy or lobectomy seem to be essential for significant and long-lasting
      seizure reduction. These procedures, however, can have considerable limitations,
      especially in patients with functional eloquent cortex adjacent to the PNH.
      Alternatively, stereotactic neurosurgery can reduce the surgical trauma.
      Presented is a 56-year-old man who became seizure-free after stereotactically
      guided radiofrequency lesioning of a solitary PNH.

PMID- 21899534
TI  - Positive shifts of the GABAA receptor reversal potential due to altered chloride
      homeostasis is widespread after status epilepticus.
AB  - PURPOSE: gamma-Aminobutyric acid (GABA)ergic transmission plays an important role
      in the initiation of epileptic activity and the generation of ictal discharges.
      The functional alterations in the epileptiform hippocampus critically depend on
      GABAergic mechanisms and cation-chloride cotransporters. METHODS: To understand
      the cellular basis of specific functional alterations in the epileptic
      hippocampus, we studied physiologic characteristics and pharmacologically
      isolated evoked GABA(A) receptor-mediated inhibitory postsynaptic currents
      (IPSCs) recorded from principal neurons in hippocampal slices from status
      epilepticus (SE) and control rats using whole-cell and gramicidin perforated
      patch-clamp recordings. KEY FINDINGS: Whereas the resting membrane potential and
      input resistance were not significantly different between control and epileptic
      tissue, the reversal potential (E(GABA) ) of IPSCs was significantly shifted to
      more positive values in SE rats with regard to the resting membrane potential.
      Pharmacologic experiments and quantitative reverse transcriptase polymerase chain
      reaction (RT-PCR) showed that the observed changes in the epileptic tissue were
      due to a decreased ratio of the main Cl(-) extrusion transporter (K(+) -Cl(-)
      cotransporter, KCC2) to the main Cl(-) uptake transporter (Na(+) -K(+) -2Cl(-)
      cotransporter, NKCC1). SIGNIFICANCE: Our results suggest that alterations of
      cation-chloride cotransporter functions, comprising a higher NKCC1 action,
      contribute to hyperexcitability within the hippocampus following SE.

PMID- 21899535
TI  - "Blinders, phenotype, and fashionable genetic analysis": setting the record
      straight for epilepsy!

PMID- 21899536
TI  - Standards for epidemiologic studies and surveillance of epilepsy.
AB  - Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic
      studies are necessary to define the full public health burden of epilepsy; to set
      public health and health care priorities; to provide information needed for
      prevention, early detection, and treatment; to identify education and service
      needs; and to promote effective health care and support programs for people with
      epilepsy. However, different definitions and epidemiologic methods complicate the
      tasks of these studies and their interpretations and comparisons. The purpose of
      this document is to promote consistency in definitions and methods in an effort
      to enhance future population-based epidemiologic studies, facilitate comparison
      between populations, and encourage the collection of data useful for the
      promotion of public health. We discuss: (1) conceptual and operational
      definitions of epilepsy, (2) data resources and recommended data elements, and
      (3) methods and analyses appropriate for epidemiologic studies or the
      surveillance of epilepsy. Variations in these are considered, taking into account
      differing resource availability and needs among countries and differing purposes
      among studies.

PMID- 21899537
TI  - Editorial: focusing on a moving target: key themes for research and practice in
      adolescent mental health.

PMID- 21899538
TI  - Loss of activated CaMKII at the synapse underlies Alzheimer's disease memory
      loss.

PMID- 21899539
TI  - Inhibition of neuronal cholesterol biosynthesis with lovastatin leads to impaired
      synaptic vesicle release even in the presence of lipoproteins or geranylgeraniol.
AB  - Cholesterol is highly enriched in the brain, and plays a key role in synapse
      formation and function. The brain does not derive cholesterol from the
      circulation; instead, the majority of cholesterol is made in glia and secreted in
      form of lipoproteins. Neurons can synthesize cholesterol, but the extent of
      neuronal cholesterol biosynthesis in the adult brain is unknown. Cholesterol
      biosynthesis inhibitors of the statin family are widely used to lower circulating
      cholesterol and cardiovascular risk. Lipophilic statins can cross the blood brain
      barrier and inhibit brain cholesterol biosynthesis with possible consequences for
      synaptic cholesterol homeostasis. We have investigated the effects of lovastatin
      on synapse maturation and synaptic vesicle release. Treatment of primary
      hippocampal neurons with low levels of lovastatin for one week reduced synapse
      density and impaired synaptic vesicle release. Neither lipoproteins nor
      geranylgeraniol fully counteracted the lovastatin-induced decrease of synaptic
      vesicle exocytosis, even when cholesterol depletion was prevented. In contrast,
      restoration of neuronal cholesterol synthesis with mevalonate prevented defects
      in vesicle exocytosis without fully normalizing neuronal cholesterol content.
      These results raise the possibility that chronic exposure of neurons to
      lipophilic statins may affect synaptic transmission, and indicate that
      hippocampal neurons need a certain level of endogenous cholesterol biosynthesis.

PMID- 21899540
TI  - Recent advances in bacteriophage therapy: how delivery routes, formulation,
      concentration and timing influence the success of phage therapy.
AB  - OBJECTIVES: Bacteriophages are bacteria-specific viruses that infect and, in the
      case of obligately lytic phages, destroy their host bacteria. Phage therapy has
      been used therapeutically to combat bacterial infections since their discovery.
      This paper reviewed recent in-vivo phage therapy studies, with a distinct focus
      on the effect of delivery routes, phage concentration and timing of
      administration on the success of the therapy. KEY FINDINGS: It was found that the
      most successful route of administration for the treatment of systemic infections
      was via the parenteral route. Oral delivery is mainly used to treat
      gastrointestinal infections. However, in some cases phages can also reach the
      systemic circulation. Local delivery (skin, ears, teeth) has proved extremely
      successful in the treatment of topical infections, as has the inhalation of
      phages for the treatment of lung infections. The ability of phages to prevent
      biofilm formation on medical devices has received much attention, mainly in the
      area of catheter coatings. This review also highlights areas in which phage
      therapy needs substantial development. Many papers were lacking in formulation
      details, with crude phage stocks being used in most cases. No phage stability
      data were included in any of the papers. SUMMARY: The review concluded that
      although phage therapy is an excellent alternative for the treatment of bacterial
      infections, optimisation of formulations and long-term stability data is required
      before it can be widely used within a clinical setting.

PMID- 21899541
TI  - Novel gel formulations with catanionic aggregates enable prolonged drug release
      and reduced skin permeation.
AB  - OBJECTIVES: The aim of this study was to investigate skin permeation rates of a
      drug substance when applied in novel gel formulations with catanionic aggregates.
      METHODS: Reference gel without catanionic aggregates was compared with
      formulations with catanionic aggregates composed of tetracaine and either sodium
      dodecyl sulphate (SDS) or capric acid. Carbomer and SoftCAT were used to compare
      the effect of different gel types to elucidate if physically cross-linked, 'self
      destructing' systems had benefits compared with classical, covalently cross
      linked, gels. KEY FINDINGS: The rheological investigation showed that the
      interactions between the SoftCAT polymer and tetracaine/SDS aggregates were
      stronger than when the tetracaine/capric acid aggregates were used. The skin
      permeation was measured ex vivo in horizontal Ussing chambers and the permeation
      of tetracaine was significantly lower when formulations with tetracaine/SDS
      aggregates were applied (P < 0.001), but not statistically different from the
      reference when capric acid was used. CONCLUSIONS: No morphological differences
      could be distinguished between the skin samples exposed to the different
      formulations or the reference. Skin permeation was compared with silicone sheet
      permeation and the results indicated that silicone sheets could be used as a
      model of skin when using these formulations.

PMID- 21899542
TI  - In-situ gel formulations of econazole nitrate: preparation and in-vitro and in
      vivo evaluation.
AB  - OBJECTIVES: This study describes the in-situ gelling of econazole nitrate
      containing thermosensitive polymers composed of poloxamer 407 and 188 as a novel
      treatment platform for vaginal candidiasis. METHODS: Aqueous thermosensitive
      formulations containing 1% of econazole nitrate and poloxamer 407 and/or 188 were
      prepared and their rheological, mechanical and drug-release properties determined
      at 20 +/- 0.1 degrees C and/or 37 +/- 0.1 degrees C. Based on their biologically
      suitable thermorheological properties, formulations containing the mixtures of
      poloxamer 407 and 188 in ratios of 15:15 (F1), 15:20 (F2) and 20:10 (F3) were
      chosen for comprehensive analysis. KEY FINDINGS: Formulations based on F3
      exhibited typical gel-type mechanical spectra (G' > G") at 37 degrees C whereas
      formulations based on F1 and F2 exhibited properties akin to weakly cross-linked
      gels. Texture profile analysis demonstrated that F3 showed the highest
      cohesiveness, adhesiveness, hardness and compressibility. No statistically
      significant differences (P > 0.5) were observed in the release of econazole
      nitrate from the formulations at pH 4.5, which in all cases followed anomalous
      diffusion kinetics. Formulations based on 20% poloxamer 407:10% poloxamer 188
      were chosen for in-vivo studies and were shown to be effective for the treatment
      of the vaginal candidiasis. Histopathologic evaluation also supported the
      effectiveness of the thermosensitive formulation administered intravaginally.
      CONCLUSION: By careful engineering of the rheological properties, in-situ
      thermosensitive gel formulations of econazole nitrate were prepared and were
      shown to be efficacious in the treatment of vaginal candidiasis.

PMID- 21899543
TI  - An investigation of the chick chorioallantoic membrane as an alternative model to
      various biological tissues for permeation studies.
AB  - OBJECTIVES: The chick chorioallantoic membrane (CAM) was explored as a biological
      membrane for use in the study of drug permeation with a Franz diffusion cell.
      METHODS: The CAM was removed from fertilized chicken eggs of embryo age 9-18
      days. The permeation profiles of nicotine through the fresh CAM were first
      obtained with a Franz diffusion cell. The permeation profiles of nicotine through
      frozen CAM, snake skin, pig skin, pig retina and pig buccal mucosa were also
      determined and compared with those of the fresh CAM. KEY FINDINGS: The
      permeability coefficient of the CAM varied with its age. The CAM at embryo age 13
      was the most robust, showing the lowest standard error in permeability. It was
      thus chosen for comparative studies with snake skin, pig skin, retina and buccal
      mucosa. The CAM was found to be most similar to the buccal mucosa in terms of
      permeation profile and permeability coefficient values. Frozen CAM was also found
      to have a higher permeability coefficient than fresh CAM. The enhanced
      permeability was attributed to freezing, which affected the integrity of the CAM
      structure. CONCLUSIONS: From the findings, CAM shows potential as an alternative
      to the pig buccal mucosa as an in-vitro buccal model. The robustness of the CAM
      for drug permeation studies is affected by its age.

PMID- 21899544
TI  - Effect of chronic supplementation with methylsulfonylmethane on oxidative stress
      following acute exercise in untrained healthy men.
AB  - OBJECTIVE: This study was conducted to assess the effects of chronic daily
      methylsulfonylmethane (MSM) supplementation on known markers of oxidative stress
      following acute bouts of exercise in untrained healthy young men. METHODS:
      Eighteen untrained men volunteered for this study. Participants were randomized
      in a double-blind placebo-controlled fashion into two groups: MSM (n = 9) and
      placebo (n = 9). The participants took supplementation or placebo daily for 10
      days before running. Participants ran 14 km. The MSM supplementation was prepared
      in water at 50 mg/kg body weight. The placebo group received water. Serum
      malondialdehyde (MDA), protein carbonyl (PC) and plasma oxidized glutathione
      (GSSG) were measured as markers of oxidative stress. The plasma-reduced
      glutathione (GSH) level and the GSH/GSSG ratio were determined as markers of
      plasma antioxidant capacity. KEY FINDINGS: Acute exercise led to elevated levels
      of serum MDA, PC and plasma GSSG. MSM supplementation maintained PC, MDA and GSSG
      at lower levels after exercise than the placebo. The plasma level of GSH and the
      ratio of GSH/GSSG were significantly higher in the MSM supplemented group.
      CONCLUSIONS: These results suggest that chronic daily oral supplementation of MSM
      has alleviating effects on known markers of oxidative stress following acute
      bouts of exercise in healthy young men.

PMID- 21899545
TI  - Proton pump inhibitors omeprazole, lansoprazole and pantoprazole induce
      relaxation in the rat lower oesophageal sphincter.
AB  - OBJECTIVES: We aimed to investigate effects of the proton pump inhibitors (PPIs)
      omeprazole, lansoprazole and pantoprazole, which are currently used for the
      treatment of hyperacidity and gastro-oesophageal reflux, on the reactivity of the
      isolated rat lower oesophageal sphincter. METHODS: Omeprazole, lansoprazole and
      pantoprazole (all 10(-9) -10(-3) m, cumulatively) were tested on carbachol
      induced (10(-6) m) contraction. In addition, the effects of PPI preincubation
      (all 10(-3) m) on the contractions induced by cumulative carbachol (10(-9) -10(
      5) m), angiotensin-2 (10(-9) -10(-5) m) or electrical field stimulation (EFS; 40
      V, 32 Hz, 1 ms, 10 s) were assessed. Finally, the effects of PPI on the
      spontaneous contractile activity of the tissue were also evaluated. KEY FINDINGS:
      PPI relaxed precontracted lower oesophageal sphincter in a concentration
      dependent manner and suppressed carbachol-, angiotensin- and EFS-induced
      contractions. Furthermore, PPI attenuated spontaneous contractile activity of the
      tissue. CONCLUSIONS: Omeprazole, lansoprazole and pantoprazole had a suppressor
      effect on lower oesophageal sphincter contractions.

PMID- 21899546
TI  - KIOM-79 inhibits aldose reductase activity and cataractogenesis in Zucker
      diabetic fatty rats.
AB  - OBJECTIVES: KIOM-79, a combination of four plant extracts, has a preventive
      effect on diabetic nephropathy and retinopathy in diabetic animal models. In this
      study, we have investigated the inhibitory effects of KIOM-79 on diabetic
      cataractogenesis. METHODS: We evaluated aldose reductase activity during
      cataractogenesis using Zucker diabetic fatty (ZDF) rat, an animal model of type 2
      diabetes. ZDF rats were treated orally with KIOM-79 (50 mg/kg body weight) once a
      day for 13 weeks. KEY FINDINGS: In vehicle-treated ZDF rats, lens opacity was
      increased, and lens fibre swelling and membrane rupture were observed. In
      addition, aldose reductase activity and aldose reductase protein expression in
      diabetic lens were markedly enhanced. However, the administration of KIOM-79
      inhibited the development of diabetic cataract through the inhibition of aldose
      reductase activity and protein expression in diabetic lenses. CONCLUSIONS: These
      observations suggested that KIOM-79 was useful against the treatment of diabetic
      cataractogenesis.

PMID- 21899547
TI  - Acteoside inhibits melanogenesis in B16F10 cells through ERK activation and
      tyrosinase down-regulation.
AB  - OBJECTIVES: Acteoside is a phenylpropanoid glycoside extracted from the leaves of
      Rehmannia glutinosa that displays various biological activities. In this study,
      we tested the effects of acteoside on tyrosinase activity and melanin
      biosynthesis in B16F10 melanoma cells. We also explored molecular mechanisms for
      the inhibition of melanogenesis observed, focusing on the signalling pathway of
      extracellular signal-regulated kinase (ERK). METHODS: The effects of acteoside
      were determined using several cell-free assay systems and B16F10 melanoma cells
      for melanin content and tyrosinase activity. To investigate effects on
      melanogenic regulatory factors we performed reverse transcription polymerase
      chain reaction, cAMP assay and Western blot analyses. KEY FINDINGS: Acteoside
      showed an inhibitory effect on tyrosinase activity and melanin synthesis in both
      cell-free assay systems and cultured B16F10 melanoma cells. Acteoside decreased
      levels of tyrosinase, tyrosinase-related protein-1 (TRP-1) and microphthalmia
      associated transcription factor (MITF) proteins, whereas it increased ERK
      phosphorylation. A specific ERK inhibitor, PD98059, abolished the acteoside
      induced down-regulation of MITF, tyrosinase and TRP-1 proteins. The ERK inhibitor
      increased tyrosinase activity and melanin production and reversed the acteoside
      induced decrease in tyrosinase activity and melanin content. In addition,
      acteoside suppressed melanogenesis induced by alpha-melanocyte-stimulating
      hormone and showed UV-absorbing effects. CONCLUSIONS: Acteoside decreased
      tyrosinase activity and melanin biosynthesis in B16F10 cells by activating ERK
      signalling, which down-regulated MITF, tyrosinase and TRP-1 production.

PMID- 21899548
TI  - Azithromycin suppresses proliferation, interleukin production and mitogen
      activated protein kinases in human peripheral-blood mononuclear cells stimulated
      with bacterial superantigen.
AB  - OBJECTIVES: Macrolide antibiotics are used for the treatment of immunological
      disorders such as psoriasis. However, few studies have investigated the
      immunoregulatory efficacy of macrolides in bacterial superantigen-stimulated
      immune cells. METHODS: The suppressive efficacies of azithromycin,
      clarithromycin, roxithromycin and prednisolone were evaluated in vitro against
      the concanavalin A- or toxic shock syndrome toxin 1 (TSST-1)-induced
      proliferation of peripheral-blood mononuclear cells (PBMCs) obtained from nine
      healthy subjects. The concentrations of six cytokines in a PBMC-culture medium
      were measured using bead-array procedures followed by flow cytometry. Cellular c
      jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)
      activity were measured using cell-based ELISA procedures. KEY FINDINGS:
      Azithromycin, clarithromycin and roxithromycin inhibited the proliferation of
      both the concanavalin A- and superantigen-stimulated PBMCs dose-dependently. The
      effect of azithromycin was the strongest, with IC50 values of less than 5 ug/ml.
      Furthermore, the suppressive efficacy of prednisolone against concanavalin A- or
      TSST-1-stimulated PBMCs was significantly promoted in combination with 5 ug/ml
      azithromycin (P < 0.002). The concentrations of TNF-alpha, interleukin (IL)-2, 
      4, -5 and -10 in the supernatant of concanavalin A- or TSST-1-stimulated PBMCs
      cultured for 72 h decreased by 65-98% in the presence of 5 ug/ml azithromycin.
      The stimulation of PBMCs with concanavalin A or TSST-1 increased cellular JNK and
      ERK activity, and 5 ug/ml azithromycin significantly attenuated the increased
      activity of JNK in the TSST-1-stimulated cells and ERK in the concanavalin A- and
      TSST-1-stimulated PBMCs, respectively (P < 0.05). CONCLUSIONS: Azithromycin
      suppresses mitogen- or superantigen-induced proliferation of PBMCs by possibly
      inhibiting both cellular JNK and ERK activity.

PMID- 21899549
TI  - Alternative therapeutic advantages of catfish bile on atopic dermatitis:
      protection of T cell-mediated skin disease via antioxidant activities.
AB  - OBJECTIVES: In the present study, we aimed to examine the anti-atopic properties
      of bile from the cat fish, Silurus asotus, to determine its possible use as a
      pharmaceutical product. METHODS: The anti-atopic activities of cat fish bile were
      examined in a non-cell antioxidant, in-vitro assay (splenocytes and mast cells)
      and a 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like mouse model.
      RESULTS: The results of these experiments revealed that Silurus asotus bile (SAB)
      scavenges radicals and protects proteins from superoxide attacks, suggesting that
      SAB suppresses the T helper (Th) type 2-skewed immune response. Th1/Th2 mRNA
      cytokines (interleukin (IL)-2, interferon (IFN)-gamma and IL-4) from mouse
      splenocytes were effectively inhibited, and the release of beta-hexosaminidase in
      RBL-2H3 mast cells was significantly suppressed by SAB. These results were
      supported by screening the Th1/Th2 cytokine mRNAs (IL-2, IFN-gamma and IL-4) from
      lymph nodes in DNCB-treated mice. More dramatic results were observed in the
      histological changes at higher SAB concentrations (5%) compared to the
      therapeutic control, visualized using hematoxylin-eosin (H&E) staining.
      CONCLUSIONS: The results presented in this study suggest that SAB may provide
      functional advantages with regard to treating atopic dermatitis because of its
      antioxidant and immune-suppressive effects.

PMID- 21899550
TI  - Mangifera indica L. extract (Vimang) and mangiferin reduce the airway
      inflammation and Th2 cytokines in murine model of allergic asthma.
AB  - OBJECTIVES: The aim was to study the effects of Mangifera indica extract and its
      major component mangiferin on lung inflammation response and Th2 cytokine
      production using a murine experimental model of allergic asthma. METHODS: BALB/c
      mice were intraperitoneally sensitized with 10 ug of ovoalbumin (OVA) adsorbed on
      aluminium hydroxide on days 0, 7 and 14. Seven days after the last injection, the
      mice were challenged with 2% aerosolized OVA inhalation for 30 min beginning on
      day 21 and continuing until day 24. To evaluate the protective effect, mice were
      orally treated with M. indica extract (50, 100 or 250 mg/kg) or mangiferin (50
      mg/kg) from days 0 to 24. Anti-OVA immunoglobulin E, interleukin (IL)-4 and IL-5
      were determined by ELISA and lungs were analysed by histology. KEY FINDINGS: M.
      indica extract and mangiferin produced a marked reduction of airway inflammation
      around vessels and bronchi, inhibition of IL-4 and IL-5 cytokines in
      bronchoalveolar lavage fluid and lymphocyte culture supernatant, IgE levels and
      lymphocyte proliferation. CONCLUSION: This is the first pre-clinical report of
      the anti-inflammatory properties of M. indica extract and mangiferin in
      experimental asthma and it could be an important part of pre-clinical requirement
      necessary for its use to complement the treatment of this complex disease.

PMID- 21899552
TI  - Leaf extract of Rhus verniciflua Stokes protects dopaminergic neuronal cells in a
      rotenone model of Parkinson's disease.
AB  - OBJECTIVES: The present study investigated the neuroprotective effects of Rhus
      verniciflua Stokes (RVS) leaf extract on rotenone-induced apoptosis in human
      dopaminergic cells, SH-SY5Y. METHODS: Cells were pretreated with RVS extract for
      1 h then treated with vehicle or rotenone for 24 h. Cell viability, cell
      cytotoxicity, cell morphology and nuclear morphology were examined by MTT assay,
      lactate dehydrogenase release assay, phase contrast microscopy and staining with
      Hoechast 33342, respectively. Reactive oxygen species were measured by 2'7'
      dichlorofluorescein diacetate and fragmented DNA was observed by TUNEL assay.
      Mitochondrial membrane potential was determined by Rhodamine 123. Pro-apoptotic
      and anti-apoptotic proteins and tyrosine hydroxylase were analysed by Western
      blotting. KEY FINDINGS: Results showed that RVS suppressed rotenone-induced
      reactive oxygen species generation, cellular injury and apoptotic cell death. RVS
      also prevented rotenone-mediated changes in Bax/Bcl-2 levels, mitochondrial
      membrane potential dissipation and Caspase 3 activation. Moreover, RVS
      pretreatment increased the tyrosine hydroxylase levels in SH-SY5Y cells.
      CONCLUSIONS: These findings demonstrate that RVS protects SH-SY5Y cells against
      rotenone-induced injury and suggest that RVS may have potential therapeutic value
      for neurodegenerative disease associated with oxidative stress.

PMID- 21899551
TI  - Flavonoids in Scutellaria immaculata and S. ramosissima (Lamiaceae) and their
      biological activity.
AB  - OBJECTIVES: The aim of this study was to investigate the flavonoid composition of
      Scutellaria immaculata and S. ramosissima (Lamiaceae) and the in-vitro biological
      activity of their extracts and flavonoids. METHODS: The flavonoid composition of
      S. immaculata (Si) and S. ramosissima (Sr) were analysed using LC-MS.
      Antimicrobial activity was studied in vitro against a range of bacteria and fungi
      using diffusion and microdilution methods. Anti-trypanosomal and cell
      proliferation inhibitory activity of the extracts and flavonoids was assessed
      using MTT. The antioxidant activity of the flavonoids and extracts were evaluated
      using DPPH* test. KEY FINDINGS: LC-MS investigation of Si and Sr plants allowed
      the identification, for the first time, of an additional 9 and 16 flavonoids,
      respectively. The methanol, chloroform and water extracts from these plants and
      six flavonoids (scutellarin, chrysin, apigenin, apigenin-7-O-glucoside,
      cynaroside and pinocembrine) exhibited significant inhibition of cell growth
      against HeLa, HepG-2 and MCF-7 cells. The chloroform extract of Sr showed potent
      cytotoxic effects with IC50 (drug concentration which resulted in a 50% reduction
      in cell viability) values of 9.25 +/- 1.07 ug/ml, 12.83 +/- 1.49 ug/ml and 17.29
      +/- 1.27 ug/ml, respectively. The highest anti-trypanosomal effect against T. b.
      brucei was shown by the chloroform extract of Sr with an IC50 (drug concentration
      which resulted in a 50% inhibition of the biological activity) of 61 ug/ml. The
      pure flavonoids showed an IC50 range between 3 and 29 um, with cynaroside as the
      most active compound with an IC50 value of 3.961 +/- 0.133 um. The chloroform
      extract of Sr has potent antimicrobial activity against Streptococcus pyogenes
      (minimum inhibitory concentration, MIC = 0.03 mg/ml). Pinocembrine exhibited a
      strong activity against the all bacteria except Escherichia coli and yeasts.
      Water extracts of Sr and Si exhibited potent antioxidant activity with IC50
      values of 5.62 +/- 0.51 ug/ml and 3.48 +/- 0.02 ug/ml, respectively. Scutellarin
      exerted stronger antioxidant activity than other flavonoids. CONCLUSIONS: This is
      the first study reporting an in-vitro biological investigation for Si and Sr.
      Especially the chloroform extract of Sr showed potent anticancer and
      antimicrobial activity. Cynaroside had a highly selective and strong cytotoxicity
      against T. b. brucei while showing only mild effects against cancer cells.

PMID- 21899553
TI  - Myrtenal inhibits acetylcholinesterase, a known Alzheimer target.
AB  - OBJECTIVES: Inhibition of acetylcholinesterase (AChE) is a common treatment for
      early stages of the most general form of dementia, Alzheimer's disease. In this
      study selected components of essential oils, which carry a variety of important
      functional groups, were tested for their in-vitro anti-acetylcholinesterase
      activity. METHODS: In-vitro anti-acetylcholinesterase activity was measured by an
      adapted version of Ellman's colorimetric assay. KEY FINDINGS: 1,8-cineole,
      carvacrol, myrtenal and verbenone apparently inhibited AChE; the highest
      inhibitory activity was observed for myrtenal (IC50 = 0.17 mm). This is the first
      study showing the AChE inhibitory activity of myrtenal. CONCLUSIONS: Our
      investigations provided evidence for the efficacy of monoterpenes as inhibitors
      of AChE.

PMID- 21899554
TI  - Contrasting wetland CH4 emission responses to simulated glacial atmospheric CO2
      in temperate bogs and fens.
AB  - Wetlands were the largest source of atmospheric methane (CH(4) ) during the Last
      Glacial Maximum (LGM), but the sensitivity of this source to exceptionally low
      atmospheric CO(2) concentration ([CO(2) ]) at the time has not been examined
      experimentally. We tested the hypothesis that LGM atmospheric [CO(2) ] reduced
      CH(4) emissions as a consequence of decreased photosynthate allocation to the
      rhizosphere. We exposed minerotrophic fen and ombrotrophic bog peatland mesocosms
      to simulated LGM (c. 200 ppm) or ambient (c. 400 ppm) [CO(2) ] over 21 months (n
      = 8 per treatment) and measured gaseous CH(4) flux, pore water dissolved CH(4)
      and volatile fatty acid (VFA; an indicator of plant carbon supply to the
      rhizosphere) concentrations. Cumulative CH(4) flux from fen mesocosms was
      suppressed by 29% (P < 0.05) and rhizosphere pore water [CH(4) ] by c. 50% (P <
      0.01) in the LGM [CO(2) ], variables that remained unaffected in bog mesocosms.
      VFA analysis indicated that changes in plant root exudates were not the driving
      mechanism behind these results. Our data suggest that the LGM [CO(2) ]
      suppression of wetland CH(4) emissions is contingent on trophic status. The
      heterogeneous response may be attributable to differences in species assemblage
      that influence the dominant CH(4) production pathway, rhizosphere supplemented
      photosynthesis and CH(4) oxidation.

PMID- 21899555
TI  - Examining the large-scale convergence of photosynthesis-weighted tree leaf
      temperatures through stable oxygen isotope analysis of multiple data sets.
AB  - The idea that photosynthesis-weighted tree canopy leaf temperature (T(candelta))
      can be resolved through analysis of oxygen isotope composition in tree wood
      cellulose (delta(18) O(wc)) has led to the observation of boreal-to-subtropical
      convergence of T(candelta) to c. 20 degrees C. To further assess the validity of
      the large-scale convergence of T(candelta), we used the isotope approach to
      perform calculation of T(candelta) for independent delta(18) O(wc) data sets that
      have broad coverage of climates. For the boreal-to-subtropical data sets, we
      found that the deviation of T(candelta) from the growing season temperature
      systemically increases with the decreasing mean annual temperature. Across the
      whole data sets we calculated a mean T(candelta) of 19.48 degrees C and an SD of
      2.05 degrees C, while for the tropical data set, the mean T(candelta) was 26.40
      +/- 1.03 degrees C, significantly higher than the boreal-to-subtropical mean. Our
      study thus offers independent isotopic support for the concept that boreal-to
      subtropical trees display conserved T(candelta) near 20 degrees C. The isotopic
      analysis cannot distinguish between the possibility that leaf temperatures are
      generally elevated above ambient air temperatures in cooler environments and the
      possibility that leaf temperature equals air temperature, whereas the leaf/air
      temperature at which photosynthesis occurs has a weighted average of near 20
      degrees C in cooler environments. Future work will separate these potential
      explanations.

PMID- 21899556
TI  - Histone modifications and expression of DAM6 gene in peach are modulated during
      bud dormancy release in a cultivar-dependent manner.
AB  - * Bud dormancy release in many woody perennial plants responds to the seasonal
      accumulation of chilling stimulus. MADS-box transcription factors encoded by
      DORMANCY ASSOCIATED MADS-box (DAM) genes in peach (Prunus persica) are implicated
      in this pathway, but other regulatory factors remain to be identified. In
      addition, the regulation of DAM gene expression is not well known at the
      molecular level. * A microarray hybridization approach was performed to identify
      genes whose expression correlates with the bud dormancy-related behaviour in 10
      different peach cultivars. Histone modifications in DAM6 gene were investigated
      by chromatin immunoprecipitation in two different cultivars. * The expression of
      DAM4-DAM6 and several genes related to abscisic acid and drought stress response
      correlated with the dormancy behaviour of peach cultivars. The trimethylation of
      histone H3 at K27 in the DAM6 promoter, coding region and the second large intron
      was preceded by a decrease in acetylated H3 and trimethylated H3K4 in the region
      of translation start, coinciding with repression of DAM6 during dormancy release.
      * Analysis of chromatin modifications reinforced the role of epigenetic
      mechanisms in DAM6 regulation and bud dormancy release, and highlighted common
      features with the vernalization process in Arabidopsis thaliana and cereals.

PMID- 21899558
TI  - Cross-cultural adaptation of the Brazilian-Portuguese version of the chronic
      urticaria quality-of-life questionnaire - CU-Q2oL.
AB  - BACKGROUND: Chronic urticaria (CU) is a debilitating skin disorder that affects
      patients' health related quality of life and the only questionnaire prepared
      specifically to CU is the Chronic Urticaria Quality of Life Questionnaire (CU
      Q(2)oL). OBJECTIVE: The purpose of this study was to cross-culturally adapt and
      validate the CU-Q(2)oL Brazilian-Portuguese version. METHODS: Forward and back
      translation by three bilingual translators followed by pre-test was used to adapt
      the questionnaire. The CU-Q(2)oL was self-administered along with the Dermatology
      Life Quality Index (DLQI) in 112 patients with CU. Disease activity was assessed
      using the Urticaria Activity Score. Factor analysis was used to identify scales
      of the Brazilian portuguese CU-Q(2)oL. Internal consistency, convergent validity
      and known-group validity was determined. Reproducibility was evaluated by
      interclass correlation coefficient (ICC). Multiple linear regression was used to
      determine the predicting factors of CU-Q(2)oL results. RESULTS: Factor analysis
      revealed a three-dimensional structure: sleep/mental status/eating (I),
      pruritus/impact on life activities (II) and swelling/limits/look (III), which
      explained 52.49% of the total variance. All scales showed excellent internal
      consistency. External construct validity was supported by correlations between
      the CU-Q(2)oL and DLQI. The tool was found to be able to differentiate between
      patients with high and low levels of urticaria activity. Test-retest reliability
      was good to excellent (ICC = 0.69-0.86). Disease severity and urticaria type were
      the only factors predicting results. CONCLUSIONS: The CU-Q(2)oL Brazilian
      portuguese version was easily filled out, well accepted by the patients,
      demonstrated an acceptable validity and reliability and might be used to evaluate
      treatment outcomes and in clinical research.

PMID- 21899557
TI  - Responses to deviants are modulated by subthreshold variability of the standard.
AB  - Auditory mechanisms automatically detect both basic features of sounds and the
      rules governing their presentation. In the oddball paradigm, the auditory system
      detects the sameness (or no-variability) rule when the same reference tone is
      consistently repeated. We used two oddball protocols, the classical one with a
      fixed reference and a modified one with a jittered reference, to determine
      whether the auditory system can detect subthreshold violations of sameness. We
      found that the response to the repeated standard was not modified by the small
      jitter. However, the response to the frequency oddball was smaller under the
      jittered protocol, indicating hypersensitivity to sameness. The sensitivity to
      jitter was largest when the oddball deviated by 8%, was smaller for 40%, and
      disappeared at 100% deviation, indicating that sensitivity to sameness is context
      dependent; namely, it is scaled with respect to the overall range of stimuli.

PMID- 21899559
TI  - Mithridates VI Eupator of Pontus and mithridatism.

PMID- 21899560
TI  - Differential expression of interleukin-32 in chronic rhinosinusitis with and
      without nasal polyps.
AB  - BACKGROUND:   Chronic rhinosinusitis (CRS) is a heterogeneous disease
      characterized by local inflammation of the upper airways and sinuses and is
      frequently divided into polypoid CRS (CRSwNP) and nonpolypoid CRS (CRSsNP).
      However, the mechanism of inflammation in CRS has still not been fully
      elucidated. The aim of the study was to investigate the role of interleukin-32
      (IL-32), a recently discovered proinflammatory cytokine, in CRS. METHODS:   We
      collected nasal epithelial cells and nasal tissue from patients with CRS and
      control subjects. We assayed mRNA for IL-32 by real-time PCR and measured IL-32
      protein using ELISA, Western blot, and immunohistochemistry. RESULTS:   The
      expression of mRNA for IL-32 was elevated in epithelial cells from uncinate
      tissue from patients with CRSsNP compared with patients with CRSwNP (P < 0.05),
      control subjects (P=0.06), and epithelial cells from nasal polyp (NP) tissue (P <
      0.05). Production of IL-32 was induced by IFN-gamma, TNF, and dsRNA in primary
      airway epithelial cells. In whole-tissue extracts, the expression of IL-32
      protein was significantly elevated in patients with CRSwNP compared with patients
      with CRSsNP and control subjects. Immunohistochemistry data showed that IL-32 was
      detected in mucosal epithelial cells and inflammatory cells in the lamina
      propria. Levels of IL-32 were correlated with the levels of CD3 and macrophage
      mannose receptor in NP tissue. Immunofluorescence data showed IL-32 co
      localization with CD3-positive T cells and CD68-positive macrophages in NPs.
      CONCLUSION:   Overproduction of IL-32 may be involved in the pathogenesis of CRS,
      although the role of IL-32 in the inflammation in CRSsNP and CRSwNP may be
      different.

PMID- 21899561
TI  - The construction of meaning by experts and would-be parents in assisted
      reproductive technology.
AB  - This article explores the construction of meaning regarding assisted reproductive
      technology by legal framers, medical practitioners and would-be parents, through
      the concept of ecology of knowledge. It is argued that these inter-relationships
      between experts and lay people can be understood in terms of the formation of a
      social structure of ecology of knowledge, which depends on local and emotional
      knowledge co-produced by medical doctors, jurists and lay people in dynamic ways
      without compromising the autonomy of medical, legal and lay knowledge and skills.
      The assessment of the benefits and risks of assisted reproductive technology
      partially represents negotiations of knowledge between these social and
      professional groups, aiming to reproduce existing relations and practices,
      particularly the social power of medicine and technology, the dominant
      perceptions about women's and men's bodies and the geneticisation of genealogy.
      These negotiations of knowledge generate new rights, new social actors, new
      scientific fields and new ways of thinking and talking about individual and
      institutional responsibilities. Ecology of knowledge comes imbued with hope,
      trust, power, credibility of institutions and moralisation whereby some citizens'
      rights may be weakened.

PMID- 21899562
TI  - Politics, welfare regimes, and population health: controversies and evidence.
AB  - In recent years, a research area has emerged within social determinants of health
      that examines the role of politics, expressed as political traditions/parties and
      welfare state characteristics, on population health. To better understand and
      synthesise this growing body of evidence, the present literature review, informed
      by a political economy of health and welfare regimes framework, located 73
      empirical and comparative studies on politics and health, meeting our inclusion
      criteria in three databases: PubMed (1948-), Sociological Abstracts (1953-), and
      ISI Web of Science (1900-). We identified two major research programmes, welfare
      regimes and democracy, and two emerging programmes, political tradition and
      globalisation. Primary findings include: (1) left and egalitarian political
      traditions on population health are the most salutary, consistent, and
      substantial; (2) the health impacts of advanced and liberal democracies are also
      positive and large; (3) welfare regime studies, primarily conducted among wealthy
      countries, find that social democratic regimes tend to fare best with absolute
      health outcomes yet consistently in terms of relative health inequalities; and
      (4) globalisation defined as dependency indicators such as trade, foreign
      investment, and national debt is negatively associated with population health. We
      end by discussing epistemological, theoretical, and methodological issues for
      consideration for future research.

PMID- 21899563
TI  - Fracture resistance of roots filled with gutta-percha or RealSeal(r).
AB  - AIM: To evaluate the vertical root fracture resistance of maxillary central
      incisors filled with different root filling materials and sealers. METHODOLOGY:
      Forty maxillary central incisor root canals were instrumented and divided
      randomly into four groups. Each group was filled using lateral compaction, with
      gutta-percha and AH Plus, gutta-percha and RealSeal((r)) sealer, RealSeal((r))
      cone and RealSeal((r)) sealer, or RealSeal((r)) cone and AH Plus, respectively.
      The roots were loaded vertically by a conical spreader tip inserted into the
      canal and attached to an Instron testing machine until root fracture occurred.
      The load at fracture and the pattern of fracture were recorded. Mechanical
      properties of both core materials were tested under compressive loading. Results
      were analysed statistically by two-way analysis of variance and post hoc Tukey's
      tests. An independent sample t-test was used to compare the mechanical properties
      of the filling materials. RESULTS: Load at fracture of roots filled with gutta
      percha and AH Plus (255 +/- 74 N) and gutta-percha and RealSeal((r)) sealer (237
      +/- 38 N) was significantly greater than those filled using the RealSeal((r))
      system (163 +/- 29 N) and RealSeal((r)) cone with AH Plus sealer (134 +/- 17 N).
      Most fracture lines were in a bucco-lingual direction. In compressive tests of
      the core materials, RealSeal((r)) had greater flow in response to load than gutta
      percha, suggesting more efficient transmission of forces to the canal wall in the
      fracture tests. CONCLUSIONS: The lower fracture resistance of roots filled using
      RealSeal((r)) is probably the result of more efficient transmission of forces
      within the canal, rather than a direct effect of the material itself.

PMID- 21899564
TI  - Overexpression of interleukin-6 and -8, cell growth inhibition and morphological
      changes in 2-hydroxyethyl methacrylate-treated human dental pulp mesenchymal stem
      cells.
AB  - AIM: To evaluate morphological features, cell growth and interleukin-6 (IL-6) and
      interleukin-8 (IL-8) secretion in expanded ex vivo human dental pulp mesenchymal
      stem cells (DP-MSCs) after exposure to 2-hydroxyethyl methacrylate (HEMA).
      METHODOLOGY:   Dental pulp mesenchymal stem cells were derived from the dental
      pulps of 10 young donors. After in vitro isolation, DP-MSCs were treated with 3
      and 5 mmol L(-1) HEMA, and after 24, 48 and 72 h of incubation, their
      morphological features, cell growth, IL-6 and IL-8 secretion were analysed.
      Differences in the cell growth and in the interleukin secretion were analysed for
      statistical significance with two-way anova tests and the Holm-Sidak method for
      multiple comparisons. RESULTS:   Dental pulp mesenchymal stem cells revealed a
      decrease in cell growth with both treatments (P < 0.05), more evident at 5 mmol
      L(-1) . Microscopic analysis displayed extensive cytotoxic effects in treated
      cells, which lost their fibroblastoid features and became retracted, even
      roundish, with a large number of granules. An up-regulation of IL-6 and IL-8 in
      treated cells cytokines was evident (P < 0.05). CONCLUSIONS:   2-Hydroxyethyl
      methacrylate exhibited cytotoxicity, inhibited cell growth and induced
      morphological changes in cultured DP-MSCs. Moreover, in treated samples, an up
      regulation of soluble mediators of inflammation such as IL-6 and IL-8 cytokines
      was found. The direct application of HEMA potentially induces an inflammation
      process that could be the starting point for toxic response and cell damage in DP
      MSCs.

PMID- 21899565
TI  - The efficacy of five techniques for removing root filling material: microscopic
      versus radiographic evaluation.
AB  - AIM:   To test and compare the efficacy of five methods for the removal of root
      filling material and to test the hypothesis that radiographs fail to represent
      the real extent of remaining material on canal walls. METHODOLOGY:   Fifty
      maxillary anterior single-rooted teeth with straight root canals were selected.
      The coronal third of each root canal was prepared with Gates-Glidden drills to
      number 3, whilst the apical two-thirds were prepared with manual K-files to size
      40. Root fillings were performed using lateral compaction with gutta-percha and
      AH-26. After full setting, the coronal third of the root filling was removed with
      Gates-Glidden drills and the teeth divided into five groups (n=10). The remaining
      root filling material was then removed with either Hedstrom files and chloroform
      (25 MUL), using size 40 as the last file, SafeSider files, using a NiTi Pleezer
      reamer with a 0.06 taper followed by size 40 reciprocating file, with or without
      chloroform, or ProTaper Universal retreatment files (D2, D3) with or without
      chloroform. Reaching working length with no more gutta-percha on the last file
      was defined as the endpoint for all procedures. The presence of remaining filling
      material was first evaluated radiographically and then by the microscopic
      evaluation of split roots. The time required to accomplish the procedure was also
      recorded. anova and anova with repeated measures were used for statistical
      analysis of the results. RESULTS:   Overall, 11-26% of the canal wall remained
      covered with filling material; no significant difference was found between the
      groups. The mechanized methods were faster than manual removal of filling
      material (P < 0.01); the use of solvent did not speed up the mechanized
      procedures. Radiographic evaluation failed to adequately and reliably detect the
      extent of filling material remaining on the canal walls, which was later observed
      by microscopic evaluation. CONCLUSIONS:   All methods left root canal filling
      material on the canal walls. Radiographic evaluation failed to detect the extent
      of remaining root filling material, which could only be detected using
      microscopy.

PMID- 21899566
TI  - Effect of intracanal irrigants on the bond strength of epoxy resin-based and
      methacrylate resin-based sealers to root canal walls.
AB  - AIM:   To assess the bond strength of Epiphany and AH Plus sealers to root canal
      walls using a push-out test after use of several endodontic irrigants.
      METHODOLOGY:   Roots of 100 maxillary canines were sectioned horizontally 5 mm
      below the cemento-enamel junction to provide 4-mm-thick dentine disks that were
      embedded in acrylic resin and had their root canals prepared with a tapered bur
      (larger diameter=2.70 mm; smaller diameter=2.30 mm; length = 4 mm). The specimens
      were randomly assigned to five groups (n=20) according to the dentine surface
      treatment: I - 1% NaOCl (30 min); II - 1% NaOCl (30 min) + 17% EDTA (5 min); III 
      17% EDTA (30 min); IV - 24% EDTA gel (30 min); V - 2% chlorhexidine gluconate
      (CHX) gel (30 min). In each group, two specimens were prepared for scanning
      electron microscopy to examine the surface of root canal dentine after use of
      each irrigant. The other 18 specimens were filled with AH plus (n = 9) or
      Epiphany (n=9) and subjected to a push-out test in an Instron machine. Data (in
      MPa) were subjected to statistical analysis by two-way anova and post-hoc Tukey
      Kramer test (P < 0.05). RESULTS:   AH Plus had a significantly higher bond
      strength (8.74 +/- 2.75) than Epiphany (6.74 +/- 3.97) (P < 0.05). One per cent
      NaOCl/17% EDTA was associated with significantly higher bond strength values
      (10.88 +/- 3.05) than the other irrigants (P < 0.05). Seventeen per cent EDTA
      (8.75 +/- 1.75), 24% EDTA gel (7.48 +/- 3.48) and 2% CHX gel (7.89 +/- 3.41) had
      intermediate values that were not significantly different from each other (P >
      0.05). One per cent NaOCl was associated with the lowest mean values (3.70 +/-
      0.86) (P < 0.05). The interaction between surface treatment and sealer revealed
      significantly higher bond strength for 24% EDTA gel with AH Plus, 2% CHX gel with
      AH Plus and 1%NaOCl/17%EDTA with Epiphany (P < 0.05). CONCLUSION:   Except for 1%
      NaOCl, the removal of smear layer with the other irrigants increased the bond
      strength of AH Plus to intracanal dentine. The use of 1% NaOCl for 30 min with
      17% EDTA as final irrigant for 5 min increased the bond strength of Epiphany.

PMID- 21899567
TI  - The influence of pressure changes on endodontically treated teeth during
      simulated dives.
AB  - AIM:   To measure and evaluate pressure changes in the pulp chambers of extracted
      teeth exposed to hyperbaric conditions during root canal treatment. METHODOLOGY: 
      A pressure sensor was inserted and sealed into the pulp chambers of extracted
      human molars (n = 6). The teeth were subjected to simulated dives to 4.5 bar in a
      diving chamber. During the simulated ascents and descents, the pressure within
      the pulp chamber was measured, and the difference between the pressure inside the
      pulp chamber and the pressure in the diving chamber was calculated. Each tooth
      underwent two dives with an intact pulp chamber, with a calcium hydroxide
      dressing, after root canal filling, and after adhesive sealing of the pulp
      chamber floor with a composite. Differences were analyzed statistically (P <
      0.05) using one-way analysis of variance (anova). RESULTS:   There were no
      significant pressure differences in teeth with an intact pulp chamber and teeth
      with a calcium hydroxide dressing. After root filling, however, the increase in
      pressure inside the pulp chamber was significantly lower (P < 0.05) than that in
      the diving chamber. After adhesive sealing of the pulp chamber floor with a
      composite, the pressure inside the pulp chamber was significantly lower (P <
      0.05) than the pressure in the diving chamber. CONCLUSIONS:   In root canal
      treatment, canal orifices should be sealed with an adhesively bonded composite
      filling before a dive. The use of a calcium hydroxide dressing after root canal
      preparation does not disqualify patients from diving.

PMID- 21899568
TI  - Nanostructured hydroxyapatite as filler for methacrylate-based root canal
      sealers.
AB  - AIM:   To evaluate the effect of different concentrations of nanostructured
      hydroxyapatite on the radiopacity, flow and film thickness of an experimental
      root canal sealer. METHODOLOGY:   An experimental dual-cured root canal sealer
      was produced with a methacrylate-based co-monomer blend. Nanostructured
      hydroxyapatite/calcium tungstate solutions (ratios 10:90, 20:80, 30:70 and 40:60)
      were added to produce the sealer. Radiopacity was evaluated using a digital
      system and an aluminium step wedge (n=5). Flow and thickness tests were conducted
      in accordance with ISO 6876 (n=3). The data were analysed using one-way anova and
      Tukey's test (alpha=0.05). RESULTS:   All groups had levels of radiopacity in
      accordance with ISO 6876. The flow of the experimental sealers was not
      significantly different (P=0.204). All groups had a film thickness in accordance
      with ISO 6876 and with no statistical difference (P = 0.654). CONCLUSION: The
      addition of up to 40% HA(nano) to root canal sealers did not alter their
      radiopacity and film thickness.

PMID- 21899569
TI  - Effect of heat stress on the expression levels of receptor activator of NF-kappaB
      ligand and osteoprotegerin in human periodontal ligament cells.
AB  - AIM:   To investigate the expression levels of the receptor activator of NF
      kappaB ligand (RANKL) and osteoprotegerin (OPG) in human periodontal ligament
      fibroblasts (PDLs) when stimulated with heat. METHODOLOGY:   Periodontal ligament
      fibroblasts were subjected to various temperature increases for 5 min and then
      maintained at 37  degrees C. After that, cell viability was determined using an
      MTT assay. The expression levels of RANKL and OPG were investigated using real
      time RT-PCR and ELISA. As a control, the cells were cultured at 37  degrees C.
      Data were analysed using one-way anova at a significant level of P = 0.05.
      Results  Cell viability was reduced significantly in the heated groups (P <
      0.05). Heat stress downregulated the mRNA expression levels of RANKL and OPG (P <
      0.05). When the cells were heated at 39  degrees C, the protein release of OPG
      was increased (P < 0.05). There were no significant differences between the
      heated groups and the control in the release of soluble RANKL (P > 0.05). The
      relative RANKL/OPG expression ratios were decreased at 39, 43 and 50  degrees C
      (P < 0.05), but increased at 47  degrees C (P < 0.05). CONCLUSIONS:   Heat
      influenced the balance between RANKL and OPG in PDLs. Low heat downregulated
      their relative ratio, whilst high heat upregulated it.

PMID- 21899570
TI  - Hepatocyte growth factor-transfected skeletal myoblasts to limit the development
      of postinfarction heart failure.
AB  - Stem cells transplanted to an injured heart affect the host myocardium
      indirectly. The cytokine hepatocyte growth factor (HGF) may play a key role in
      this paracrine activity. We hypothesized that HGF-overexpressing stem cells would
      restore cardiac function after myocardial infarction (MI). Because there is a
      high rate of cell death when injecting the cells intramyocardially, we used
      scaffold-based cell transfer. Skeletal myoblasts (SkMs) were isolated and
      expanded from newborn Lewis rats. Cells were transfected with pcDNA3-huHGF and
      seeded on polyurethane (PU) scaffolds or diluted in medium for cell injection.
      The seeded scaffolds were transplanted in rats two weeks after MI (group: PU-HGF
      SkM) or the infection solution was intramyocardially injected (group: Inj-HGF
      SkM). Two groups (Inj-SkM and PU-SkM) have been prepared with untransfected cells
      and sham group without any cell therapy served as control (n = 10 each group). At
      the beginning of treatment (baseline) and six weeks later, hemodynamic parameters
      were assessed. At the end of the study, histological analysis was employed. In
      sham animals we detected a decrease in systolic and diastolic function during the
      observation time. Treatment with untransfected myoblasts did not lead to any
      significant changes in hemodynamic parameters between the intervention and six
      weeks later. In group PU-HGF-SkM, systolic parameters like dP/dt(max), dP/dt(min)
      and isovolumic contraction improved significantly from baseline to study end.
      Some diastolic parameters were inferior as compared to baseline (SB-Ked, pressure
      half time [PHT], Tau). In group Inj-HGF-SkM, only PHT was impaired as compared to
      preinterventional values. Histological analysis showed significantly more
      capillaries in the infarction border zone in groups PU-HGF-SkM than in sham and
      Inj-SkM group. The infarction size was not affected by the therapy. Transplanting
      HGF-transfected myoblasts after MI can limit the development of ventricular
      dysfunction. Scaffold-based therapy in combination with gene therapy accelerates
      this capacity. This hemodynamic amelioration is accompanied by
      neovascularization, but not by smaller infarction sizes.

PMID- 21899571
TI  - Mechanical cavopulmonary assistance of a patient-specific Fontan physiology:
      numerical simulations, lumped parameter modeling, and suction experiments.
AB  - This study investigated the performance of a magnetically levitated,
      intravascular axial flow blood pump for mechanical circulatory support of the
      thousands of Fontan patients in desperate need of a therapeutic alternative. Four
      models of the extracardiac, total cavopulmonary connection (TCPC) Fontan
      configuration were evaluated to formulate numerical predictions: an idealized
      TCPC, a patient-specific TCPC per magnetic resonance imaging data, and each of
      these two models having a blood pump in the inferior vena cava (IVC). A lumped
      parameter model of the Fontan physiology was used to specify boundary conditions.
      Pressure-flow characteristics, energy gain calculations, scalar stress levels,
      and blood damage estimations were executed for each model. Suction limitation
      experiments using the Sylgard elastomer tubing were also conducted. The pump
      produced pressures of 1-16 mm Hg for 2000-6000 rpm and flow rates of 0.5-4.5
      L/min. The pump inlet or IVC pressure was found to decrease at higher rotational
      speeds. Maximum scalar stress estimations were 3 Pa for the nonpump models and
      290 Pa for the pump-supported cases. The blood residence times for the pump
      supported cases were shorter (0.9 s) as compared with the nonsupported
      configurations (2.5 s). However, the blood damage indices were higher (1.5%) for
      the anatomic model with pump support. The pump successfully augmented pressure in
      the TCPC junction and increased the hydraulic energy of the TCPC as a function of
      flow rate and rotational speed. The suction experiments revealed minimal
      deformation (<3%) at 9000 rpm. The findings of this study support the continued
      design and development of this blood pump.

PMID- 21899573
TI  - Overview on "Chinese-Finnish workshop on biomanufacturing and evaluation
      techniques".

PMID- 21899572
TI  - Hemodynamic evaluation of the Avalon Elite bi-caval dual lumen cannulae.
AB  - In previous studies, we have evaluated the hemodynamic properties of selected
      oxygenators, pumps (centrifugal and roller), and single lumen cannulae. Because
      the dual lumen cannulae are widely used in veno-venous extracorporeal life
      support (ECLS) and are receiving popularity due to their advantages over the
      single lumen cannulae, we evaluated the flow ranges and pressure drops of three
      different sizes of Avalon Elite dual lumen cannulae (13Fr, 16Fr, and 19Fr) in a
      simulated neonatal ECLS circuit primed with human blood. The experimental ECLS
      circuit was composed of a RotaFlow centrifugal pump, a Capiox BabyRX05
      oxygenator, 3 ft of 1/4-in venous and arterial line tubing, an Avalon Elite dual
      lumen cannula, and a soft reservoir as a pseudo-right atrium. All experiments
      were conducted at 37 degrees C using an HCU 30 heater-cooling unit and with human
      blood at a hematocrit of 36%. The blood pressure in the pseudo-right atrium was
      continuously monitored and maintained at 4-5 mm Hg. For each cannula, pump flow
      rates and pressures at both the arterial and venous sides were recorded at
      revolutions per minute (RPMs) from 1750 to 3750 in 250 intervals. For each RPM,
      six data sets were recorded for a total of 162 data sets. The total volume of the
      system was 300 mL. The flow range for the 13Fr, 16Fr, and 19Fr cannulae were from
      228 to 762 mL/min, 478 to 1254 mL/min, and 635 to 1754 mL/min, respectively. The
      pressure drops at the arterial side were higher than the venous side at all
      tested conditions except at 1750 rpm for the 19Fr cannula. The results of this
      study showed the flow ranges and the pressure drops of three different sized dual
      lumen cannulae using human blood, which is more applicable in clinical settings
      compared with evaluations using water.

PMID- 21899574
TI  - Abdominal hernia repair with a decellularized dermal scaffold seeded with
      autologous bone marrow-derived mesenchymal stem cells.
AB  - Surgeons usually use synthetic polymer meshes for abdominal wall hernia repair.
      However, synthetic polymer meshes exhibit a lack of growth and related
      complications. In this study, we produced a tissue-engineered patch for abdominal
      hernia repair. Autologous bone-marrow-derived mesenchymal stem cells (BMSCs) were
      isolated and proliferated in vitro; decellularized dermal scaffolds (DSs) were
      prepared using enzymatic process; and then BMSCs were seeded onto the DSs for the
      construction of tissue-engineered patches. Under general anesthesia, rabbits
      underwent creation of abdominal wall defects and which were repaired with BMSC
      seeded DSs, acellular DSs, and skin sutures only, respectively. Animals were
      sacrificed after 2 months for assessing the histological and gross examination.
      Abdominal hernias were absent in animals repaired with cell-seeded group, and
      abdominal hernias or bulges appeared in all animals repaired with acellular
      group. All the animals that were not repaired died within 10 days. The cell
      seeded implants were thicker and indicated good angiogenesis compared with that
      of the acellular implants, both in histological and gross examination. The tissue
      engineered patches prepared with BMSCs seeding on DSs can be used for abdominal
      wall hernia repair.

PMID- 21899575
TI  - Radial artery pseudoaneurysm in a Maine Coon cat.
AB  - OBJECTIVE: To report the diagnosis and treatment of a radial artery
      pseudoaneurysm in a cat. STUDY DESIGN: Clinical report. ANIMAL: Maine Coon cat (8
      year-old neutered male). METHODS: Ultrasonographic and angiographic examination
      of a fluctuant, nonpainful, 3 cm * 1.5 cm subcutaneous swelling on the
      craniomedial distal aspect of the right radius that occurred 40 days after
      suspected cat bite trauma was consistent with a radial artery pseudoaneurysm.
      After ligation of the radial artery proximal to the lesion, the pseudoaneurysm
      was surgically excised. RESULTS: The excised tissue had hemorrhage and fibrin
      surrounded by a thick fibrous granulating capsule of variably mature fibroblasts
      and focal areas of inflammatory cells (lymphocytes, plasma cells, and
      macrophages) consistent with a pseudoaneurysm. Surgical excision resulted in
      resolution of clinical signs. CONCLUSIONS: Ultrasonography enabled prompt,
      noninvasive diagnosis of pseudoaneurysm. Angiography or computed tomography may
      be useful to aid diagnosis and assess the collateral blood supply to the manus
      before surgical treatment.

PMID- 21899576
TI  - Total hip replacement with dorsal acetabular rim augmentation using the SOP(TM)
      implant and polymethylmethacrylate cement in seven dogs with dorsal acetabular
      rim deficiency.
AB  - OBJECTIVE: To describe a surgical technique for reinforced augmentation of the
      dorsal acetabular rim (DAR) using a string-of-pearls (SOPTM) locking plate and
      polymethylmethacrylate (PMMA) bone cement, and to report clinical outcome in 7
      dogs. STUDY DESIGN: Case series. ANIMALS: Dogs (n=7). METHODS: Medical records
      (November 2009-April 2010) of 7 dogs with large DAR deficits, that had total hip
      replacement (THR) with reinforced augmentation of the DAR using a SOPTM plate and
      PMMA were evaluated retrospectively. Reinforced augmentation of the DAR involved
      anchorage of a precontoured 2.0 or 2.7 mm SOPTM plate dorsal to the acetabulum
      followed by application of PMMA cement to cover the reamed acetabulum and plate.
      Cemented acetabular components were used. Implant associated complications were
      recorded and >=6-month follow-up obtained. RESULTS: In all dogs, lameness
      improved at medium-term reassessment (median, 8 months; range, 6-11 months).
      Complications included transient sciatic neurapraxia in 2 dogs, which resolved by
      3 months. CONCLUSIONS: Reinforced augmentation of the DAR using a SOPTM plate and
      PMMA cement may facilitate placement of acetabular THR component implantation in
      dogs with severe DAR insufficiency.

PMID- 21899577
TI  - String-of-pearls locking plate and cerclage wire stabilization of periprosthetic
      femoral fractures after total hip replacement in six dogs.
AB  - OBJECTIVE: To report use of, and outcome after, string-of-pearls (SOPTM) plate
      and multiple cerclage wire fixation for treatment of periprosthetic femoral
      fractures (PFF) associated with total hip replacement (THR) in dogs. STUDY
      DESIGN: Case series. ANIMALS: Dogs (n=6) with PFF after THR. METHODS: Clinical
      records (2005-2010) and radiographic evaluations of dogs that had PFF associated
      with THR, treated with a SOPTM plate and cerclage wires were retrospectively
      reviewed. Clinical and radiographic postoperative assessments were performed 4,
      12, and 24 weeks postoperatively. Telephone follow-up was performed >12 months
      postoperatively. RESULTS: Three fractures occurred intraoperatively and 3
      occurred postoperatively. One SOPTM failed at 2 weeks necessitating revision
      using 2 parallel SOPTM implants. One dog was euthanatized because of quadriceps
      muscle tie-down at 6 weeks. Other dogs were free of lameness with full range of
      motion of the stifle and hip joints at final clinical examination, and positive
      outcomes were maintained at >12 month telephone questionnaire. There was no
      evidence of implant failure and positive evidence of fracture healing at final
      radiographic follow-up. CONCLUSIONS: Stabilization resulted in bone healing in 5
      dogs; failure in 1 dog may be attributable to technical error. Optimal technical
      guidelines for use of the SOPTM in this circumstance are unknown, particularly
      where fracture configuration varies.

PMID- 21899578
TI  - Standing ovariectomy in mares using a transvaginal natural orifice transluminal
      endoscopic surgery (NOTES(r)) approach.
AB  - OBJECTIVE: To develop and assess the feasibility of standing transvaginal Natural
      Orifice Transluminal Endoscopic Surgery (NOTES(r)) ovariectomy in the mare. STUDY
      DESIGN: Descriptive study. ANIMALS: Mares (n=10). METHODS: The technique was
      developed in 6 mares and then evaluated in a short-term study in 4 mares.
      Abdominal access was developed using controlled access vaginal cannula placement
      under endoscopic guidance. With viewing provided by a flexible endoscope,
      hemostasis, and transection of ovarian pedicles was performed using a customized
      bipolar vessel-sealing device. The ovaries were retrieved and the colpotomy was
      sutured. Surgical time, intra-, and postoperative complications were recorded.
      Necropsy was performed immediately after surgery in 6 mares and 15 days after
      surgery in 4 mares to assess short-term complications. RESULTS: After the
      instruments and techniques were developed, transvaginal NOTES(r) ovariectomy was
      successfully performed. Analgesia during the procedure was adequate in all cases.
      The visual field provided by the endoscope was acceptable. The customized 60 cm
      vessel-sealing device provided good hemostasis and a comfortable working length.
      Intraoperative complications included difficult viewing that prolonged operative
      time and inability to remove the second ovary in 1 mare. Postoperative recovery
      was excellent. Postmortem findings of 1 true positive microbial culture, elevated
      cell counts in abdominal fluid, and adhesion formation raise questions that must
      be addressed in future studies. CONCLUSION: Using specialized instruments,
      transvaginal NOTES(r) ovariectomy is technically feasible in mares.

PMID- 21899579
TI  - Significance of the rdar and bdar morphotypes in the hydrophobicity and
      attachment to abiotic surfaces of Salmonella Sofia and other poultry-associated
      Salmonella serovars.
AB  - AIMS: To investigate the relative role of the red dry and rough (rdar) and brown
      dry and rough (bdar) morphotypes on hydrophobicity and ability to attach to
      abiotic surfaces of poultry-associated Salmonella strains with a focus on S.
      Sofia. METHODS AND RESULTS: Cellulose synthase gene null mutants were constructed
      in five Salmonella strains converting them from rdar to bdar morphotypes. One S.
      Sofia null mutant displayed reduced hydrophobicity and attachment to Teflon(r)
      relative to its parent strain. The S. Virchow and S. Infantis null mutants
      attached less well to glass relative to their parent strains. CONCLUSIONS: The
      rdar or bdar morphotype may influence S. Sofia persistence but did not explain
      why bdar strains predominate in this serotype. SIGNIFICANCE AND IMPACT OF THE
      STUDY: This work provides some insight into why some Salmonella strains survive
      in poultry environments and may ultimately contribute to their control.

PMID- 21899580
TI  - Microbiological contamination of digested products from anaerobic co-digestion of
      bovine manure and agricultural by-products.
AB  - AIMS: This study was performed to investigate the microbiological contamination
      of digestate product (DP) obtained from the anaerobic co-digestion of bovine
      manure and agricultural by-products. METHODS AND RESULTS: Microbiological
      analyses were performed on bovine manure, fresh DP, liquid and solid fractions
      and stored liquid fraction of DP. A statistically significant reduction of faecal
      bacterial indicator was found after anaerobic digestion except for enterococci.
      After liquid/solid DP separation, bacteria tend to be concentrated in the solid
      fraction. Storage does not seem to influence the indicator parameters, except for
      enterococci. Escherichia coli O157:H7 and Yersinia were not found in any samples
      analysed. Salmonella was rarely detected in DP samples and its derivates, while
      Listeria monocytogenes was encountered in many samples. CONCLUSIONS: The results
      obtained indicate that the hygienic quality of DP is for almost all
      microbiological parameters better than that of the bovine manure (range of
      reduction 1.6-3.1 log10) and suggest the need to identify specific pathogen
      indicators related to the hygienic characteristics of DPs. SIGNIFICANCE AND
      IMPACT OF THE STUDY:   This study highlights that the anaerobic co-digestion of
      bovine manure and agricultural by-products in a field-scale biogas plant does not
      increase human health risk with respect to the use of animal manure for
      agricultural fertilization.

PMID- 21899581
TI  - Modelling the inhibitory effect of copper sulfate on the growth of Penicillium
      expansum and Botrytis cinerea.
AB  - AIMS: This study aimed to investigate the effect of copper sulfate (from 0 to 8
      mmol kg(-1)) on radial growth rate and lag time of two moulds responsible for
      vine grapes spoilage: Penicillium expansum strain 25.03 and Botrytis cinerea,
      strains BC1 and BC2. METHODS AND RESULTS: A new model was developed to describe
      tailing and shoulders in the inhibition curves. Because of tailing, the minimum
      inhibitory concentration (MIC), was not defined as the concentration at which no
      growth was observed, but as the concentration at which the lag time was infinite.
      The concentrations at which MU = MU(opt)/2, (Cu50), were in the range of 2.2-2.6
      mmol kg(-1). Radial growth rate of P. expansum and the reciprocal of the lag time
      were linearly correlated (r = 0.84). In contrast, in the range 0-4 mmol kg(-1),
      an inhibition of growth of B. cinerea was observed whereas germination remained
      unaffected (i.e. the lag time was constant). In the range 4-8 mmol kg(-1) , the
      radial growth rate of B. cinerea was almost constant (c. 1 mm day(-1)), but
      germination was inhibited (i.e. the lag time was increased). CONCLUSIONS: The MIC
      values were 4.7 mmol kg(-1) for P. expansum, 8.2 and 7.3 mmol kg(-1) for B.
      cinerea strain BC1 and BC2, respectively, demonstrating that some isolates of
      these moulds are resistant to copper. SIGNIFICANCE AND IMPACT OF THE STUDY:
      Copper concentrations at 4 mmol kg(-1) would be sufficient to control the
      development of these isolates, but the toxicity of copper should be extended to
      other isolates and evaluated in vineyards.

PMID- 21899582
TI  - Meta-analysis: predictors of rebleeding after endoscopic treatment for bleeding
      peptic ulcer.
AB  - BACKGROUND: Determining the risk of rebleeding after endoscopic therapy for
      peptic ulcer bleeding (PUB) may be useful for establishing additional haemostatic
      measures in very high-risk patients. AIM: To identify predictors of rebleeding
      after endoscopic therapy. METHODS: Bibliographic database searches were performed
      to identify studies assessing rebleeding after endoscopic therapy for PUB. All
      searches and data abstraction were performed in duplicate. A parameter was
      considered to be an independent predictor of rebleeding when it was detected as
      prognostic by multivariate analyses in >=2 studies. Pooled odds ratios (pOR) were
      calculated for prognostic variables. RESULTS: Fourteen studies met the
      prespecified inclusion criteria. Pre-endoscopic predictors of rebleeding were:
      (i) Haemodynamic instability: significant in 9 of 13 studies evaluating the
      variable (pOR: 3.30, 95% CI: 2.57-4.24); (ii) Haemoglobin value: significant in 2
      of 10 (pOR: 1.73, 95% CI: 1.14-2.62) and (iii) Transfusion: significant in two of
      six (pOR not calculable). Endoscopic predictors of rebleeding were: (i) Active
      bleeding: significant in 6 of 12 studies (pOR: 1.70, 95% CI: 1.31-2.22); (ii)
      Large ulcer size: significant in 8 of 12 studies (pOR: 2.81, 95% CI: 1.98-4.00);
      (iii) Posterior duodenal ulcer location: significant in four of eight studies
      (pOR: 3.83, 95% CI: 1.38-10.66) and (iv) High lesser gastric curvature ulcer
      location: significant in three of eight studies (pOR: 2.86; 95% CI: 1.69-4.86).
      CONCLUSIONS: Major predictors for rebleeding in patients receiving endoscopic
      therapy are haemodynamic instability, active bleeding at endoscopy, large ulcer
      size, ulcer location, haemoglobin value and the need for transfusion. These risk
      factors may be useful for guiding clinical management in patients with PUB.

PMID- 21899583
TI  - Randomised clinical trial: the synbiotic food supplement Probiotical vs. placebo
      for acute gastroenteritis in children.
AB  - BACKGROUND: Some probiotic strains reduce the duration of acute diarrhoea. As a
      result of strain and product specificity, each product needs support by clinical
      data. AIM: In children with acute diarrhoea, to test the efficacy of the
      synbiotic food supplement Probiotical (Streptoccoccus thermophilus, Lactobacillus
      rhamnosus, Lactobacillus acidophilus, Bifidobacterium lactis, Bifidobacterium
      infantis, fructo-oligosaccharides). The primary end-points were duration of
      diarrhoea and the number of children that had a normalised stool consistency.
      METHOD: A total of 111 children with acute diarrhoea (median age 40 months) were
      included in this randomised, prospective placebo-controlled parallel clinical
      trial in primary health care. All children were treated with oral rehydration
      solution ad libitum and with the synbiotic (n=57) or placebo (n = 54). RESULTS:
      The median duration of diarrhoea was 3 days (IQ 25-75: 2-4 days) in the
      Probiotical group, compared with 4 days (IQ 25-75: 4-5 days) in the placebo group
      (P<0.005). The number of children with normal stool consistency (defined as stool
      Bristol score <=4) was higher in the synbiotic group on days 2 and 3 [21 vs. 2%
      (P<0.001) and 50 vs. 24% (P<0.001) respectively]. Less additional medication
      (antipyretics, antiemetics, antibiotics) was administered in the synbiotic group.
      Physicians were globally more satisfied with the synbiotic food supplement
      treatment than with placebo (P=0.005). One patient in the placebo group was
      hospitalised. CONCLUSION: The median duration of diarrhoea was significantly 1
      day shorter in the synbiotic than in the placebo group, associated with decreased
      prescription of additional medications.

PMID- 21899584
TI  - Meta-analysis: the effects of Lactobacillus rhamnosus GG supplementation for the
      prevention of healthcare-associated diarrhoea in children.
AB  - BACKGROUND: In children, healthcare-associated diarrhoea, in particular, due to
      rotavirus, may prolong the hospital stay and increase medical costs, prompting
      interest in effective, low-cost, preventive strategies. AIM: To review
      systematically data on the efficacy of administering Lactobacillus rhamnosus GG
      (LGG) for the prevention of healthcare-associated diarrhoea. METHODS: MEDLINE,
      EMBASE, Health Source: Nursing/Academic Edition, the Cochrane Library, trial
      registries and proceedings of major meetings were systematically searched for
      randomised controlled trials (RCTs) performed in children aged 1 month to 18
      years that compared administration of LGG with placebo or no intervention. Two
      reviewers assessed studies for inclusion and risk of bias and extracted the data.
      Outcome measures included the incidences of healthcare-associated diarrhoea and
      rotavirus gastroenteritis. If appropriate, meta-analyses were carried out using
      the fixed effects model. RESULTS: Three RCTs involving 1092 children were
      included. Compared with placebo, LGG administration for the duration of hospital
      stay was associated with significantly lower rates of diarrhoea (two RCTs, n =
      823, relative risk, RR 0.37, 95% confidence interval, CI 0.23-0.59) and
      symptomatic rotavirus gastroenteritis (three RCTs, n = 1043, RR 0.49, 95% CI 0.28
      0.86). There was no significant difference between the LGG and the control groups
      in the incidence of asymptomatic rotavirus infection, duration of hospitalisation
      or duration of diarrhoea. LGG was well tolerated, and no harms were reported in
      any of the trials. CONCLUSION: In hospitalised children, the administration of
      Lactobacillus rhamnosus GG compared with placebo has the potential to reduce the
      overall incidence of healthcare-associated diarrhoea, including rotavirus
      gastroenteritis.

PMID- 21899585
TI  - TGFBI gene mutation in a Chinese pedigree with Reis-Bucklers corneal dystrophy.
AB  - PURPOSE: To characterize the molecular defects in the TGFBI gene in a Chinese
      family with Reis-Bucklers corneal dystrophy (RBCD), and to study the relationship
      between the gene mutations and the clinical manifestations. METHODS: Four
      generations of this family with RBCD were enrolled in the study. In addition to
      ophthalmic and histopathological examinations, polymerase chain reaction (PCR)
      amplification and analysis of nucleotide sequencing of exons 4, 12, 14 of TGFBI
      were performed. RESULTS: The clinical manifestations of the disease were
      characterized by geographic opacities in the subepithelial layers and anterior
      stroma of the cornea. Confocal microscopy images of the cornea showed focal hyper
      reflective materials deposited in the subepithelium and anterior stroma. It was
      confirmed by histopathology that Bowman's membrane was mainly replaced by
      extracellular fibril material, which extended downwards into the superficial
      corneal stroma. Molecular genetic analysis revealed a single heterozygous G>T
      change at nucleotide 124 in exon 4 of TGFBI in all members (22) of the pedigree
      affected with RBCD, but not in the unaffected members. CONCLUSIONS: A p.Arg124Leu
      mutation of the TGFBI gene was detected in this Chinese pedigree with Reis
      Bucklers corneal dystrophy. The phenotype of Reis-Bucklers corneal dystrophy in
      this family belongs to the geographic type. The molecular genetic studies
      combined with histopathology may be useful for the accurate diagnosis of this
      type of corneal dystrophy.

PMID- 21899586
TI  - TLR2 and TLR4 gene promoter methylation status during chronic periodontitis.
AB  - AIM: The objective of this study was to analyse the status of DNA methylation in
      the promoter region of the toll-like receptor (TLR)2 and TLR4 genes in gingival
      tissue samples from healthy subjects, smokers and non-smokers affected by chronic
      periodontitis. MATERIAL AND METHODS: Genomic DNA and total RNA were purified from
      gingival tissue using the TRIZOL reagent protocol. Genomic DNA was then digested
      by methylation-sensitive restriction enzymes, amplified by polymerase chain
      reaction (PCR), electrophoresed on a 10% polyacrylamide gel and stained using
      SYBR Gold. Real-time PCR was also performed to verify the transcript levels.
      RESULTS: The CpG dinucleotides analysed were observed to be unmethylated in the
      majority of DNA samples of the three groups and statistical differences were not
      found among groups (p>0.05). However, a trend towards methylation was observed in
      the TLR2 HhaI site in the samples of the periodontitis non-smoker groups. In
      fact, the analysis of all CpG sites together shows which complete methylation is
      observed in the shortest level in the samples of periodontitis non-smoker group.
      The analysis of transcript levels demonstrated no difference among groups
      (p>0.05). CONCLUSION: The results demonstrated major unmethylation of the TLR4
      gene promoter in all groups. However, the results for the TLR2 gene promoter are
      inconclusive; this gene was found as a mosaic of methylated and unmethylated DNA
      in the majority of samples of the three groups and we also observed a trend
      towards the DNA methylation of CpG sites recognized by the HhaI enzyme.

PMID- 21899587
TI  - Oral arteriovenous hemangioma in patient with hepatitis C.

PMID- 21899588
TI  - Agminated cellular neurothekeoma.
AB  - Cellular neurothekeoma represents a benign, slow-growing neoplasm that typically
      occurs as a solitary lesion on the face, neck or arm. Reports of multiple lesions
      are rare. To our knowledge, multiple lesions occurring as eruptive clusters
      localized to a single anatomical site has not been previously reported. This
      report details a case of an agminated cellular neurothekeoma occurring on the
      nose of a 28-year-old man. Recognition of multiple localized eruptive lesions of
      cellular neurothekeoma is important in order to facilitate correct diagnosis and
      avoid unnecessary treatment.

PMID- 21899589
TI  - Genitogluteal porokeratosis involving the scrotum: an unusual presentation of an
      uncommon disease.
AB  - Porokeratosis represents a heterogeneous group of keratinization disorders
      typified by the presence of annular plaques with distinct, raised borders that
      include cornoid lamellae. Histopathologically, a cornoid lamella is a column of
      parakeratotic scale overlying an epidermal invagination that displays nearby
      dyskeratotic keratinocytes and loss of the granular layer. Porokeratosis
      ptychotropica constitutes a rare variant that classically presents as a plaque in
      the gluteal cleft that mimics a dermatitis and microscopically contains numerous
      cornoid lamellae. We report a 28 year-old man with a two-month history of scrotal
      burning and itching associated with the development of multiple thin red plaques
      with distinct elevated borders and a pebbled appearance. Histopathological
      examination revealed psoriasiform acanthosis and multiple cornoid lamellae, which
      is consistent with a diagnosis of porokeratosis ptychotropica. Our patient's
      presentation may represent a distinct variant with clinical features of verrucous
      porokeratosis and histopathological features of porokeratosis ptychotropica which
      may suggest that the finding of multiple cornoid lamellae is not unique to
      porokeratosis ptychotropica.

PMID- 21899590
TI  - Follicular mucinosis in a mycosis fungoides-like hypersensitivity syndrome
      induced by oxcarbamazepine.

PMID- 21899591
TI  - Persistent pigmented purpuric dermatitis: granulomatous variant.
AB  - The persistent pigmented purpuric dermatitides (PPPD) are a spectrum of
      dermatologic disorders characterized by petechial and pigmented macules usually
      confined to the lower limbs. Their etiology is unknown and several clinical
      variants are recognized. At the microscopic level they are characterized by
      angiocentric lymphocytic inflammation, red blood cell extravasation and
      hemosiderin deposition. A granulomatous variant of the PPPD has recently been
      described and to date eleven cases have been reported in the literature. In
      contrast to the conventional type, this variant is characterized
      histopathologically by ill-defined, non-necrotizing granulomata admixed with the
      lymphocytic inflammatory background. Although initially the granulomatous variant
      of the PPPD was thought to occur only in Asian patients, this sole racial
      predilection has not been substantiated. A tenuous association with
      hyperlipidemia has been noted but this requires further study. The principal
      importance of recognizing this entity lies in the need to include it in the
      histopathological differential diagnosis of granulomatous dermal infiltrates. We
      report here an additional patient with the granulomatous variant of PPPD and
      elaborate on this entity in the context of existing information in the
      literature.

PMID- 21899592
TI  - Etanercept-induced cutaneous and pulmonary sarcoid-like granulomas resolving with
      adalimumab.
AB  - A 59-year-old female with rheumatoid arthritis on etanercept therapy presented
      with a 7-cm-large subcutaneous forearm mass. Multiple smaller nodules
      subsequently developed on the upper and lower extremities. Except for a new
      cough, the patient was systemically well. Biopsy of the mass showed sarcoidal
      type granulomatous inflammation with nodular aggregations of non-necrotizing
      epithelioid histiocytes in the subcutis. A chest computed tomography (CT) scan
      showed mediastinal adenopathy consistent with pulmonary sarcoidosis. Etanercept
      was discontinued, and the patient was started on adalimumab for rheumatoid
      arthritis control. The cutaneous nodules fully resolved in 6 months with no
      additional treatment. A 4-month follow-up CT scan showed significant regression
      of mediastinal adenopathy. The patient has since been maintained on adalimumab
      therapy for 2 years with no recurrence of sarcoid-like manifestations. Biologic
      response modifiers targeting tumor necrosis factor alpha (TNFalpha) are effective
      treatments of chronic inflammatory conditions such as rheumatoid arthritis and
      psoriasis. TNFalpha represents a major cytokine in granuloma formation, and
      TNFalpha inhibitors are sometimes efficacious in the treatment of sarcoidosis.
      Paradoxically, there is a small volume of literature implicating TNFalpha
      inhibitors in the development of sarcoid-like disease. We present this case to
      promote the recognition of TNFalpha inhibitor-induced sarcoidosis and to
      illustrate the wide clinicopathologic differential of sarcoidal type granulomas.

PMID- 21899594
TI  - Nurse practitioners and physician assistants in Dutch hospitals: their role,
      extent of substitution and facilitators and barriers experienced in the
      reallocation of tasks.
AB  - AIMS:   This paper is a report of a study exploring the role of nurse
      practitioners and physician assistants, the extent of substitution and the
      barriers and facilitators experienced by them as a consequence of substitution in
      public hospitals. BACKGROUND:   Nurse practitioners and physician assistants are
      emerging worldwide. However, despite the large amount of evidence showing the
      added value of these professionals, little evidence is available concerning the
      role, extent of substitution and facilitators and barriers experienced by them as
      a consequence of substitution. METHODS:   Interviews were conducted and a
      questionnaire was completed by 43 nurse practitioners and 13 physician assistants
      employed in public hospitals in the south of the Netherlands in 2007. Results. 
      Nurse practitioners and physician assistants performed a broad spectrum of tasks,
      but differed significantly in the time spent and the kind of tasks performed.
      Nurse practitioners spent 25% (10.4 hours; SD = 5.5) and physician assistants 40%
      (18.7 hours; SD = 7.6) of their time on medical procedures. They both also
      performed new tasks or tasks for which there previously was insufficient
      capacity. Many of them experienced policy/organizational, legal, financial or
      facility problems in the reallocation of tasks. CONCLUSION:   Nurse practitioners
      and physician assistants have wide ranging but different responsibilities in
      public hospitals. By performing medical procedures and new tasks or tasks for
      which there was not enough capacity, they function as substitutes and supplements
      for doctors. However, barriers are affecting the extent of substitution. The
      challenge ahead is to remove the barriers experienced by nurse practitioners and
      physician assistants.

PMID- 21899595
TI  - The past, present and future of nursing education in the People's Republic of
      China: a discussion paper.
AB  - AIM:   This article presents a discussion of nursing education development in the
      People's Republic of China in its historical, economic and sociopolitical
      contexts. BACKGROUND:   China has a population of 1.3 billion with about 2.18
      million nurses. With the recent surging economic and social development in China,
      nursing education has undergone transformation changes in the past two decades.
      DATA SOURCES:   Online bibliographical databases from 1990 to 2010 were searched
      including CINAHL, MEDLINE, Wan Fang Data and Chinese National Knowledge
      Infrastructure. Search terms included nursing education, China and development.
      METHODS:   Thematic analysis and narrative synthesis were used to identify and
      report themes from literature. RESULTS:   Database searches yielded 1674 papers,
      and 34 met the inclusion criteria for review. The standard of nursing education
      varies greatly in different parts of China, because of its huge size and
      population, with pre-registration programmes offered at the secondary, associate
      degree and baccalaureate level. Multi-level nursing education is one of the major
      barriers for professional development. There is a need to upgrade the pre
      registration education to at least associate degree level. There is also a need
      to enhance graduate nursing education at master and doctoral level to prepare
      advanced practice nurses, nurse scientists and nursing faculty. conclusion:  The
      challenges for nursing education development in China are echoed and encountered
      in many parts of the world. The experience in China and the lessons learned would
      be relevant to developing countries. Nursing in China must continue to develop in
      parallel to international trends. Promoting communication and maintaining
      international links are important for the global development of nursing practice.

PMID- 21899596
TI  - The experiences of women (65-74 years) living with a long-term condition in the
      shadow of ageing.
AB  - AIMS: This paper reports on a study that explored experiences of women (65-74
      years) as they grow older while living with a long-term condition. The phenomenon
      of focus was 'ageing with a long-term condition', rather than the experience of
      developing a long-term condition after reaching older adulthood. BACKGROUND:
      People with long-term conditions are living into older age. There is limited
      literature on the nexus of ageing with a long-term condition. It is known that
      ageing shapes and is shaped by women's experiences of living with a long-term
      condition. METHODS: In this interpretive descriptive study, nine women
      participated in a series of three focus groups held in 2007 and 2008. Transcripts
      were analysed thematically and participants given the opportunity to respond to
      the analysis. FINDINGS: 'In the shadow of ageing' was the overarching theme. The
      women reported that although their long-term condition remained the referent
      point in their daily lives, for others including health professionals, the focus
      was on their appearance and the effects of older age. To overcome the back
      grounding of their long-term condition, the women used 'strategies already-in
      place'; it became 'just another thing to deal with'. Ageing, however, remained 'a
      privilege'. CONCLUSION: If health professionals focus on age and its concomitant
      effects, rather than a woman's long-term condition, they are at risk of
      delivering inappropriate care. They need to be prepared to advocate for the
      special needs of older women who live with a long-term condition and remain
      cognizant of the women's resourcefulness and expertise developed over time.

PMID- 21899597
TI  - Recurrent aphthous ulcers--a Toll-like receptor-mediated disease?
AB  - BACKGROUND: Recurrent aphthous ulcer (RAU) is characterized by acute and painful
      inflammatory ulcerations, which heal spontaneously but tend to recur. Many
      pathogens have been proposed as causative agents, but none has been consistently
      proven. According to our hypothesis, RAU is an autoinflammatory disorder
      triggered by pathogen-associated molecular patterns (PAMPs) shared by different
      pathogenic and commensal microbes. METHODS: PAMP-reactive Toll-like receptors
      (TLRs) were mapped in oral epithelium in healthy controls compared to RAU.
      RESULTS: In controls, the superficial epithelium formed a TLR(-), a PAMP non
      reactive physical barrier zone, but all TLRs were found deeper in the epithelium,
      usually restricted to suprabasal and basal cell layers. In RAU, the epithelial
      TLR polarity was lost: TLRs 1, 2, 5, 7, and 8 were found throughout the
      epithelium, but also TLRs 4, 6, and 10 extended higher up than normally, whereas
      TLR-3 was almost lost in RAU. In RAU lesions, connective tissue stroma was
      heavily infiltrated by TLR(+) inflammatory cells. CONCLUSIONS: Normal TLR
      architecture prevents inflammatory responses against normal microbes but still
      contains a deep TLR(+) , PAMP-reactive dormant defense zone. In RAU, the TLR(+),
      PAMP-reactive zone extends to surface or subsurface exposed to microbial PAMPs.
      TLR reactivity is further enhanced by recruitment of inflammatory leukocytes
      forming a new deep line of defense. The organization of the TLR system in healthy
      mucosa and its changes in RAU are compatible with active pathogenic involvement
      of TLRs, which together with the typical clinical picture and course suggest that
      RAU is a TLR-mediated disease.

PMID- 21899598
TI  - Expression and regulation of murine SPINK12, a potential orthologue of human
      LEKTI2.
AB  - A balanced proteolytic activity in the epidermis is vital to maintain epidermal
      homoeostasis and barrier function. Distinct protease-inhibitor systems are
      operating in different epidermal layers. In the uppermost layer, the stratum
      corneum, kallikrein-like proteases and their inhibitors are responsible for
      desquamation of the cornified keratinocytes, thus regulating the integrity of the
      epidermal barrier. Following discovery and characterisation of the human
      multidomain inhibitor LEKTI (lympho-epithelial Kazal-type-related inhibitor,
      encoded by hspink5), several new members of the Kazal-type inhibitor family have
      been identified. Here we describe expression and regulation of murine SPINK12, a
      potential orthologue of human LEKTI2. Its expression was analysed by RT-PCR and
      immunohistochemistry revealing organ-specific pattern with high level of
      expression in the epidermis and several epithelia including the stomach, kidney
      and uterus. In addition, mSPINK12 expression in the epidermis of skin at
      footpads, where stratification is markedly pronounced, was several folds higher
      than in the abdominal epidermis. mSPINK12 mRNA levels were not affected by any
      cytokines tested while treatment of primary murine keratinocytes with the
      combination of calcium and sorbitol resulted in a strong increase in its mRNA. It
      appears that mspink12 is especially expressed in the epidermal areas with thick
      skin and that its regulation generally responds to differentiation signals.
      mrSPINK12 shows an inhibitory activity against murine keratinocyte-derived
      trypsin-like proteolytic activity, thus, the protein does appear orthologous to
      human LEKTI2 and may play an role in the regulation of epithelial cell functions.

PMID- 21899599
TI  - Meta-analysis of studies of a specific delivery mode for a modified-carbohydrate
      diet.
AB  - BACKGROUND: Obesity is highly prevalent throughout the world. Although modified
      carbohydrate diets (MCDs) comprise one popular approach, questions remain about
      their utility for weight loss. The objective of the present study was to conduct
      a meta-analysis of randomised controlled trials (RCTs) of a specific MCD compared
      with various control diets on weight loss. METHODS: Data from four RCTs (three
      obtained from the sponsor and one indentified through literature searches) were
      included. Intent-to-treat analyses were conducted using multiple imputation to
      handle missing data, where possible. Because inter-study heterogeneity was
      demonstrated with fixed-effects meta-analysis, a random-effects meta-analysis
      also was conducted. RESULTS: When considered separately, all four studies showed
      greater reduction in body weight with the MCD compared to control diets at 12
      week follow-up; the results at 24 weeks (available for three of the studies) were
      not as consistent. Results for body mass index (BMI) were similar. Greater
      reductions in waist circumference with the MCD were seen at either time point in
      only one study. When fixed-effects meta-analysis was applied, significantly
      greater reductions in weight, BMI and waist circumference with the MCD at both 12
      weeks (1.66 kg, 0.53 kg m(-2) and 1.02 cm, respectively) and 24 weeks (1.20 kg,
      0.43 kg m(-2) and 0.69 cm, respectively) were evident. Random-effects meta
      analysis revealed similar results; however, the 24-week difference for a
      reduction in waist circumference was no longer statistically significant.
      CONCLUSIONS: Meta-analysis of individual RCT results demonstrated consistent
      benefits of this MCD compared to control diets on weight loss up to 24 weeks and
      waist circumference up to 12 weeks.

PMID- 21899600
TI  - SPARC/osteonectin, an endogenous mechanism for targeting albumin to the blood
      cerebrospinal fluid interface during brain development.
AB  - Specialized populations of choroid plexus epithelial cells have previously been
      shown to be responsible for the transfer of individual plasma proteins from blood
      to the cerebrospinal fluid (CSF), contributing to their characteristically high
      concentrations in CSF of the developing brain. The mechanism of this protein
      transfer remains elusive. Using a marsupial, Monodelphis domestica, we
      demonstrate that the albumin-binding protein SPARC (osteonectin/BM-40/culture
      shock protein) is present in a subset of choroid plexus epithelial cells from its
      first appearance, throughout development, and into adulthood. The synthesis of
      SPARC by the lateral ventricular plexus was confirmed with real-time PCR. The
      expression level of SPARC was higher in plexuses of younger than older animals.
      Western blot analysis of the gene product confirmed the quantitative PCR results.
      The co-localization of SPARC and albumin shown by immunocytochemistry and its
      cellular location indicate that this glycoprotein may act as a recognition site
      for albumin. In addition, the numbers of SPARC-immunopositive cells and its
      expression were responsive to experimental changes of albumin concentration in
      the blood. It is suggested that SPARC may be one of the molecules that govern the
      uptake and delivery of proteins from blood to the CSF. The results also confirm
      that protein transfer across the blood-CSF barrier is developmentally and
      physiologically regulated.

PMID- 21899602
TI  - Dissecting mechanisms of reconsolidation: octopamine reveals differences between
      appetitive and aversive memories in the crab Chasmagnathus.
AB  - Ample evidence suggests that, when reactivated by a reminder, a consolidated
      memory may return to a labile state and needs to be stabilized again in order to
      persist, a process known as reconsolidation. In a previous study, performed in
      the crab Chasmagnathus, we found a dual role for the biogenic amine octopamine
      (OA) during memory consolidation. On the one hand, it was necessary for
      appetitive memory formation and, on the other, it had a deleterious effect on
      aversive memory consolidation. Thus, OA could be a good candidate to dissect the
      neurochemical mechanisms of appetitive and aversive reconsolidation. Here, we
      initially characterized the reconsolidation of an appetitive memory. Then, we
      compared appetitive reconsolidation with its aversive counterpart regarding the
      implication of OA in these processes, and contrasted them with previous findings
      obtained in the consolidation phase. Our results demonstrate that appetitive
      reconsolidation takes place when animals are re-exposed to the training context,
      as shown by the amnesic effect of cycloheximide when applied before the reminder.
      In addition, the no-reinforcement during the reminder is a necessary condition
      for appetitive reconsolidation to occur. Remarkably, appetitive reconsolidation
      is neither impaired by OA receptor antagonists nor facilitated by exogenous OA,
      whereas aversive reconsolidation can be interfered with by OA administration.
      Thus, our results indicate that appetitive reconsolidation does not involve OA
      signaling, while aversive reconsolidation is negatively modulated by OA. All in
      all, these results could constitute a step towards the identification of
      particular features of appetitive and aversive reconsolidation.

PMID- 21899601
TI  - Computational modelling of 5-HT receptor-mediated reorganization of the brainstem
      respiratory network.
AB  - Brainstem respiratory neurons express the glycine alpha(3)  receptor (Glyalpha(3)
      R), which is a target of modulation by several serotonin (5-HT) receptor
      agonists. Application of the 5-HT(1A)  receptor (5-HT(1A) R) agonist 8-OH-DPAT
      was shown (i) to depress cellular cAMP, leading to dephosphorylation of
      Glyalpha(3) R and augmentation of postsynaptic inhibition of neurons expressing
      Glyalpha(3) R (Manzke et al., 2010) and (ii) to hyperpolarize respiratory neurons
      through 5-HT-activated potassium channels. These processes counteract opioid
      induced depression and restore breathing from apnoeas often accompanying
      pharmacotherapy of pain. The effect is postulated to rely on the enhanced
      Glyalpha(3) R-mediated inhibition of inhibitory neurons causing disinhibition of
      their target neurons. To evaluate this proposal and investigate the neural
      mechanisms involved, an established computational model of the brainstem
      respiratory network (Smith et al., 2007), was extended by (i) incorporating
      distinct subpopulations of inhibitory neurons (glycinergic and GABAergic) and
      their synaptic interconnections within the Botzinger and pre-Botzinger complexes
      and (ii) assigning the 5-HT(1A) R-Glyalpha(3) R complex to some of these
      inhibitory neuron types in the network. The modified model was used to simulate
      the effects of 8-OH-DPAT on the respiratory pattern and was able to realistically
      reproduce a number of experimentally observed responses, including the shift in
      the onset of post-inspiratory activity to inspiration and conversion of the
      eupnoeic three-phase rhythmic pattern into a two-phase pattern lacking the post
      inspiratory phase. The model shows how 5-HT(1A) R activation can produce a
      disinhibition of inspiratory neurons, leading to the recovery of respiratory
      rhythm from opioid-induced apnoeas.

PMID- 21899603
TI  - A retrospective cohort study of dermatological problems observed in paediatric
      intensive care unit.
AB  - BACKGROUND: Dermatological manifestations are often encountered in paediatric
      intensive care units (PICU). Spectrum of dermatological problems that may arise
      in critically ill children in intensive care unit remains unknown. OBJECTIVES:
      The aim of this study was to find out the burden of dermatological problems and
      to describe the proportional distribution of paediatric dermatoses in ICU set-up.
      METHODS: In a retrospective cohort study, we analysed all types of paediatric
      dermatological conditions manifesting in children admitted to a tertiary level
      ICU in South India. RESULTS: During the study period of 25 months, 1180 new cases
      were admitted to PICU. A total of 318 children with 361 skin manifestations were
      observed. Majority of the skin lesions were minor and were secondary to systemic
      disease. Infection was the leading cause of dermatoses in ICU. Dengue infection
      was detected in 64% of total cases included in the study. Stevens-Johnson
      syndrome was the only primary dermatological condition leading to PICU admission
      in the present cohort. CONCLUSIONS: The spectrum and proportional distribution of
      skin conditions in children differ from adult ICU-data. Further large-scale
      investigations are needed to define the characteristics and distribution of
      infections along with other disease conditions leading to ICU-admissions and
      mortality among critically ill paediatric patients.

PMID- 21899604
TI  - Roles of p53 and p27(Kip1) in the regulation of neurogenesis in the murine adult
      subventricular zone.
AB  - The tumor suppressor protein p53 (Trp53) and the cell cycle inhibitor p27(Kip1)
      (Cdknb1) have both been implicated in regulating proliferation of adult
      subventricular zone (aSVZ) cells. We previously reported that genetic ablation of
      Trp53 (Trp53-/-) or Cdknb1 (p27(Kip1-/-) ) increased proliferation of cells in
      the aSVZ, but differentially affected the number of adult born neuroblasts. We
      therefore hypothesized that these molecules might play non-redundant roles. To
      test this hypothesis we generated mice lacking both genes (Trp53-/- ;p27(Kip1-/-)
      ) and analysed the consequences on aSVZ cells and adult neuroblasts.
      Proliferation and self-renewal of cultured aSVZ cells were increased in the
      double mutants compared with control, but the mice did not develop spontaneous
      brain tumors. In contrast, the number of adult-born neuroblasts in the double
      mutants was similar to wild-type animals and suggested a complementation of the
      p27(Kip1-/-) phenotype due to loss of Trp53. Cellular differences detected in the
      aSVZ correlated with cellular changes in the olfactory bulb and behavioral data
      on novel odor recognition. The exploration time for new odors was reduced in
      p27(Kip1-/-) mice, increased in Trp53-/- mice and normalized in the double Trp53
      /- ;p27(Kip1-/-) mutants. At the molecular level, Trp53-/- aSVZ cells were
      characterized by higher levels of NeuroD and Math3 and by the ability to generate
      neurons more readily. In contrast, p27(Kip1-/-) cells generated fewer neurons,
      due to enhanced proteasomal degradation of pro-neural transcription factors.
      Together, these results suggest that p27(Kip1) and p53 function non-redundantly
      to modulate proliferation and self-renewal of aSVZ cells and antagonistically in
      regulating adult neurogenesis.

PMID- 21899605
TI  - Change in the balance of excitatory and inhibitory midline fiber crossing as an
      explanation for the hopping phenotype in EphA4 knockout mice.
AB  - Neuronal networks in the spinal cord termed central pattern generators (CPGs) are
      responsible for the generation of rhythmic movements, such as walking. The axon
      guidance molecule EphA4 has been suggested to play a role in the configuration of
      spinal CPG networks in mammals. In EphA4 knockout (EphA4-KO) mice, the normal
      alternating walking pattern is replaced by a rabbit-like hopping gait, which can
      be reproduced when locomotor-like activity is induced in the isolated spinal
      cord. This hopping phenotype has been explained by an abnormal midline crossing
      of ipsilateral axons. Here, we investigated the nature of this overcrossing in
      heterozygous EphA4 (EphA4(lacZ/+) ) mice that showed normal alternating gait and
      homozygous EphA4 (EphA4(lacZ/lacZ) ) mice with hopping gait. Localized lesions
      showed that the hopping phenotype is maintained by fibers crossing in the ventral
      commissure. Using transgenic mouse lines in which glutamatergic, GABAergic and
      glycinergic neurons are intrinsically labeled, we showed a significant increase
      in the number of crossing excitatory beta-galactosidase-positive neurons and a
      decrease in the number of inhibitory neurons crossing the midline in
      EphA4(lacZ/lacZ)  mice compared with EphA4(lacZ/+)  mice. These results show that
      the hopping phenotype is the result of a change in the balance between excitatory
      and inhibitory signals across the midline and that EphA4-positive neurons play an
      essential role in the mammalian CPG.

PMID- 21899606
TI  - Establishment of diagnostic criteria for feline nonflea-induced hypersensitivity
      dermatitis.
AB  - Hypersensitivity dermatitides (HD) are commonly seen in cats, and they are
      usually caused by environmental, food and/or flea allergens. Affected cats
      normally present with one of the following clinical reaction patterns: head and
      neck excoriations, usually symmetrical self-induced alopecia, eosinophilic skin
      lesions or miliary dermatitis. Importantly, none of these clinical presentations
      is considered to be pathognomonic for HD skin diseases, and the diagnosis of HD
      is usually based on the exclusion of other pruritic diseases and on a positive
      response to therapy. The objectives of this study were to propose sets of
      criteria for the diagnosis of nonflea-induced HD (NFHD). We recruited 501 cats
      with pruritus and skin lesions and compared clinical parameters between cats with
      NFHD (encompassing those with nonflea, nonfood HD and those with food HD), flea
      HD and other pruritic conditions. Using simulated annealing techniques, we
      established two sets of proposed criteria for the following two different
      clinical situations: (i) the diagnosis of NFHD in a population of pruritic cats;
      and (ii) the diagnosis of NFHD after exclusion of cats with flea HD. These
      criteria sets were associated with good sensitivity and specificity and may be
      useful for homogeneity of enrolment in clinical trials and to evaluate the
      probability of diagnosis of NFHD in clinical practice. Finally, these criteria
      were not useful to differentiate cats with NFHD from those with food HD.

PMID- 21899607
TI  - The homologous HD-Zip I transcription factors HaHB1 and AtHB13 confer cold
      tolerance via the induction of pathogenesis-related and glucanase proteins.
AB  - Plants deal with cold temperatures via different signal transduction pathways.
      The HD-Zip I homologous transcription factors HaHB1 from sunflower and AtHB13
      from Arabidopsis were identified as playing a key role in such cold response. The
      expression patterns of both genes were analyzed indicating an up-regulation by
      low temperatures. When these genes were constitutively expressed in Arabidopsis,
      the transgenic plants showed similar phenotypes including cell membrane
      stabilization under freezing treatments and cold tolerance. An exploratory
      transcriptomic analysis of HaHB1 transgenic plants indicated that several
      transcripts encoding glucanases and chitinases were induced. Moreover, under
      freezing conditions some proteins accumulated in HaHB1 plants apoplasts and these
      extracts exerted antifreeze activity in vitro. Three genes encoding two
      glucanases and a chitinase were overexpressed in Arabidopsis and these plants
      were able to tolerate freezing temperatures. All the obtained transgenic plants
      exhibited cell membrane stabilization after a short freezing treatment. Finally,
      HaHB1 and AtHB13 were used to transiently transform sunflower and soybean leading
      to the up-regulation of HaHB1/AtHB13-target homologues thus indicating the
      conservation of cold response pathways. We propose that HaHB1 and AtHB13 are
      involved in plant cold tolerance via the induction of proteins able to stabilize
      cell membranes and inhibit ice growth.

PMID- 21899609
TI  - Informing your patients about their medicines: a daily challenge.

PMID- 21899608
TI  - Two glycosyltransferases involved in anthocyanin modification delineated by
      transcriptome independent component analysis in Arabidopsis thaliana.
AB  - To identify candidate genes involved in Arabidopsis flavonoid biosynthesis, we
      applied transcriptome coexpression analysis and independent component analyses
      with 1388 microarray data from publicly available databases. Two
      glycosyltransferases, UGT79B1 and UGT84A2 were found to cluster with anthocyanin
      biosynthetic genes. Anthocyanin was drastically reduced in ugt79b1 knockout
      mutants. Recombinant UGT79B1 protein converted cyanidin 3-O-glucoside to cyanidin
      3-O-xylosyl(1->2)glucoside. UGT79B1 recognized 3-O-glucosylated
      anthocyanidins/flavonols and uridine diphosphate (UDP)-xylose, but not 3,5-O
      diglucosylated anthocyanidins, indicating that UGT79B1 encodes anthocyanin 3-O
      glucoside: 2''-O-xylosyltransferase. UGT84A2 is known to encode sinapic acid: UDP
      glucosyltransferase. In ugt84a2 knockout mutants, a major sinapoylated
      anthocyanin was drastically reduced. A comparison of anthocyanin profiles in
      ugt84a knockout mutants indicated that UGT84A2 plays a major role in
      sinapoylation of anthocyanin, and that other UGT84As contribute the production of
      1-O-sinapoylglucose to a lesser extent. These data suggest major routes from
      cyanidin 3-O-glucoside to the most highly modified cyanidin in the potential
      intricate anthocyanin modification pathways in Arabidopsis.

PMID- 21899610
TI  - British pharmacy professionals' beliefs and participation in continuing
      professional development: a review of the literature.
AB  - OBJECTIVES  Continuing professional development (CPD) has potential to be useful
      in pharmacy revalidation but past uptake and attitudes to CPD in Great Britain
      (GB) need to be mapped. This review examines published literature to chart the
      participation and beliefs of pharmacy professionals towards CPD in GB in a decade
      that had seen a formal transition from continuing education to CPD. METHODS  A
      comprehensive review of the published literature was conducted to identify
      studies of the uptake of, or attitudes towards, CPD cross different sectors of
      pharmacy in GB from 2000 to 2010. KEY FINDINGS  Twenty-two studies were included
      and analysed, including 13 research papers, six conference papers, two news items
      reporting survey outcomes and one commissioned study. Eight barriers to CPD were
      identified as: time, financial costs and resource issues, understanding of CPD,
      facilitation and support for CPD, motivation and interest in CPD, attitudes
      towards compulsory CPD, system constraints, and technical problems. Pharmacy
      professionals on the whole agreed with the principle of engaging with CPD but
      there was little evidence to suggest widespread and wholehearted acceptance and
      uptake of CPD, essential for revalidation. CONCLUSIONS  If CPD is to succeed,
      people's beliefs and attitudes must be addressed by recognising and modifying
      perceived barriers through a combination of regulatory, professional, work
      related and personal channels. A number of recommendations are made. Direct
      experience of effective CPD in the absence of perceived barriers could impact on
      personal development, career development and patient benefit thus strengthening
      personal beliefs in the value of CPD in an iterative manner.

PMID- 21899611
TI  - Treatment experience of people with obstructive sleep apnoea seeking continuous
      positive airways pressure device provision through community pharmacies: a role
      for pharmacists?
AB  - OBJECTIVES  This study aimed to explore the unique experiences of people with
      obstructive sleep apnoea (OSA) who source their treatment through community
      pharmacies. METHODS  A qualitative study employing the phenomenological approach
      was used. In-depth semi-structured interviews with a purposive convenience sample
      of 20 participants were conducted. Twenty participants were recruited from
      community pharmacies offering continuous positive airways pressure (CPAP) device
      provision and a teaching hospital in Sydney, Australia. Interviews were digitally
      recorded and transcribed verbatim, coded using Nvivo8 software and analysed based
      on the 'framework' method. KEY FINDINGS  The quality and delivery of information
      at diagnosis was reported to have been inappropriate for participants' personal
      needs. Many barriers emerged in regards to CPAP use, consistent with current
      literature. Participants' self-reported individual styles, coping practices and
      health beliefs appeared to be the most influential factors in CPAP uptake and
      adherence, regardless of mechanical advancements and environmental support. High
      satisfaction was expressed with CPAP obtainment from pharmacy services listing
      convenience and good service as notable characteristics. CONCLUSIONS  Community
      pharmacies have the potential to increase OSA awareness and improve optimal usage
      of CPAP. Psychosocial based models of adherence intervention could potentially be
      implemented through CPAP providers, including the community pharmacy, to address
      some of these factors which impede CPAP adherence.

PMID- 21899612
TI  - Pharmacist prescribing in primary care: the views of patients across Great
      Britain who had experienced the service.
AB  - OBJECTIVE  To evaluate the views of patients across primary care settings in
      Great Britain who had experienced pharmacist prescribing. METHODS  All Royal
      Pharmaceutical Society of Great Britain (RPSGB) prescribers (n = 1622) were
      invited to participate. Those consenting were asked to invite up to five
      consecutive patients who had experienced their prescribing to participate.
      Patients were mailed one questionnaire and a reminder. The questionnaire included
      five sections: demographics; you and your pharmacist prescriber; you and your
      general practitioner; your views and experiences based on your most recent
      pharmacist prescriber consultation; and additional views. KEY FINDINGS  Of the
      482 (29.7%) pharmacists who responded, 92 (19.1%) were eligible to participate,
      of whom 49 (53.3%) consented. Of those excluded, 193 (49.5%) were prescribing in
      secondary care and 171 (43.8%) were not prescribing. Between September 2009 and
      March 2010, 143 patients were recruited. Patient response rate was 73.4% (n =
      105/143). Consultation settings were largely general practice (85.7%) or
      community pharmacy (11.4%). Attitudes were overwhelmingly positive with the vast
      majority agreeing/strongly agreeing that they were totally satisfied with their
      consultation and confident that their pharmacist prescribed as safely as their
      general practitioner (GP). Pharmacists were considered approachable and thorough,
      and most would recommend consulting a pharmacist prescriber. A slightly smaller
      majority would prefer to consult their GP if they thought their condition was
      getting worse and a small minority felt that there had been insufficient privacy
      and time for all their queries to be answered. CONCLUSIONS  Patients were
      satisfied with, and confident in the skills of, pharmacist prescribers. However,
      the sample was small, may be biased and the findings lack generalisability.

PMID- 21899613
TI  - Cost analysis for reimbursement-rate setting of hospital pharmaceutical services
      in Thailand.
AB  - OBJECTIVES  This study aimed to develop a hospital pharmaceutical service model,
      together with a costing template for unit cost analysis and to analyse unit costs
      of hospital pharmaceutical services. METHODS  The study was designed on the basis
      of activity-based costing. A model of the services was set up by consensus of the
      working group. Pharmaceutical services among the study hospitals were
      standardised. A Microsoft Excel-based costing template was developed. Finally,
      the costing template was used for the unit cost analysis. Sensitivity analysis
      and descriptive statistics were used for further analysis. KEY FINDINGS  Four
      general and seven regional hospitals participated in the study. Hospital
      pharmaceutical services were divided into nine supporting activities and nine
      patient-service activities. Unit costs of drug dispensing per prescription by
      regional hospitals were approximately double that of general hospitals. In
      contrast, the cost of aseptic dispensing per item in regional hospitals was lower
      than those in general hospitals. In comparing the unit costs from standard labour
      costs with those from actual labour costs, both increases and decreases were
      found. CONCLUSIONS  Costing and the use of Microsoft Excel can be applied to the
      development of a costing template for unit cost analysis of hospital
      pharmaceutical services. This programme can provide accurate unit costs for
      services. The results can be used when considering pharmacy service
      reimbursement, efficiency and service development.

PMID- 21899614
TI  - Cost analysis for efficient management: diabetes treatment at a public district
      hospital in Thailand.
AB  - OBJECTIVE  The study estimated cost of illness from the provider's perspective
      for diabetic patients who received treatment during the fiscal year 2008 at
      Waritchaphum Hospital, a 30-bed public district hospital in Sakhon Nakhon
      province in northeastern Thailand. METHODS  This retrospective, prevalence-based
      cost-of-illness study looked at 475 randomly selected diabetic patients,
      identified by the World Health Organization's International Classification of
      Diseases, 10th revision, codes E10-E14. Data were collected from the hospital
      financial records and medical records of each participant and were analysed with
      a stepwise multiple regression. KEY FINDINGS  The study found that the average
      public treatment cost per patient per year was US$94.71 at 2008 prices. Drug cost
      was the highest cost component (25% of total cost), followed by inpatient cost
      (24%) and outpatient visit cost (17%). A cost forecasting model showed that
      length of stay, hospitalization, visits to the provincial hospital, duration of
      disease and presence of diabetic complications (e.g. diabetic foot complications
      and nephropathy) were the significant predictor variables (adjusted R(2) =
      0.689). CONCLUSIONS  According to the fitted model, avoiding nephropathy and foot
      complications would save US$19 386 and US$39 134 respectively per year. However,
      these savings are missed savings for the study year and the study hospital only
      and not projected savings, as that would depend on the number of diabetic
      patients managed in the year, the ratio of complicated to non-complicated cases
      and effectiveness of the prevention programmes. Nonetheless, given the high
      avoidable cost associated with complications of diabetes, healthcare providers in
      Thailand should focus on initiatives that delay the progression of complications
      in diabetic patients.

PMID- 21899615
TI  - A qualitative study of physicians' and nurses' experiences of multidisciplinary
      collaboration with pharmacists participating at case conferences.
AB  - OBJECTIVES  Previous studies have revealed a range of drug-related problems for
      nursing home and hospital patients. Different attempts to reduce drug-related
      problems have been tested. Medication reviews performed by pharmacists and
      subsequent presentation of findings at case conferences is one of these methods.
      Physicians' and nurses' experiences from multidisciplinary collaboration with
      pharmacists have to a lesser degree been investigated. This study aims to
      describe how Norwegian physicians and nurses experience collaborating with
      pharmacists at case conferences to reduce drug-related problems in elderly
      patients. METHODS  This was a qualitative interview study using systematic text
      condensation. The setting was nursing homes (long-term care) and hospital wards
      (gerontology and rheumatology). Four physicians and eight nurses participated and
      the main outcome was physicians' and nurses' experiences of multidisciplinary
      collaboration with pharmacists. KEY FINDINGS  Organizational problems were
      experienced including, among others, what professional contribution team members
      could expect from pharmacists and what professional role the pharmacist should
      have in the multidisciplinary team. Both professions reported that ambiguities as
      to when and if the pharmacist was supposed to attend their regular meetings
      resulted in some aggravation. On the other hand, the participants valued
      contributions from pharmacists with regard to pharmaceutical skills, and felt
      that this raised awareness on prescribing quality. CONCLUSIONS  Physicians and
      nurses valued the pharmacists' services and reported that this collaboration
      improved patients' drug therapy. However, before implementing this service in
      nursing homes there is a need to make an organizational framework for this
      collaboration to support the professional role of the pharmacist.

PMID- 21899616
TI  - Severity and probability of harm of medication errors intercepted by an emergency
      department pharmacist.
AB  - OBJECTIVES  The objective of this study was to evaluate the severity and
      probability of harm of medication errors (MEs) intercepted by an emergency
      department pharmacist. The phases of the medication-use process where MEs were
      most likely to be intercepted were determined. METHODS  The emergency department
      was staffed with a full-time pharmacist during the 7-month study period. The MEs
      that were intercepted by the pharmacist were recorded in a database. Each ME in
      the database was independently scored for severity and probability of harm by two
      pharmacists and one physician investigator who were not involved in the data
      collection process. KEY FINDINGS  There were 237 ME interceptions by the
      pharmacist during the study period. The final classification of MEs by severity
      was as follows: minor (n = 42; 18%), significant (n = 160; 67%) and serious (n =
      35; 15%). The final classification of MEs by probability of harm was as follows:
      none (n = 13; 6%), very low (n = 96; 41%), low (n = 84; 35%), medium (n = 41;
      17%) and high (n = 3; 1%). Inter-rater reliability for classification was as
      follows: error severity (agreement = 75.5%, kappa = 0.35) and probability of harm
      (agreement = 76.8%, kappa = 0.42). The MEs were most likely to be intercepted
      during the prescribing phase of the medication-use process (n = 236; 90.1%).
      CONCLUSIONS  A high proportion of MEs intercepted by the emergency department
      pharmacist are considered to be significant or serious. However, a smaller
      percentage of these errors are likely to result in patient harm.

PMID- 21899617
TI  - Characteristics of clinical decision support alert overrides in an electronic
      prescribing system at a tertiary care paediatric hospital.
AB  - CONTEXT  Electronic prescribing (EP) systems are advocated as a solution to
      minimise medication errors. Benefits in patient safety are often as a result of
      some clinical decision support (CDS) within the system. OBJECTIVE  To study the
      characteristics of the CDS alerts generated within a commercially available EP
      system in use at a tertiary care paediatric hospital in the UK. METHODS 
      Retrospective review and characterisation of CDS alerts recorded in the EP system
      over 1 year. RESULTS  A total of 16 182 conflict alerts were recorded when
      ordering 26 836 items, of which 3507 (13 alerts per 100 prescription orders (95%
      confidence interval, 12.8 to 13.6)) were visible to the user. Eighty nine percent
      (3119/3507) of all visible alerts were overridden by the user at point of
      prescribing. Drug-allergy conflict alerts were the most accepted, and exact drug
      duplication alerts the least. CONCLUSION  We found a high incidence of alert
      override, which is undesirable but consistent with that reported in the
      literature. The results suggest that the underlying algorithms for alert
      generation in many EP systems are not specific and need to be reviewed.

PMID- 21899618
TI  - Pharmacists subjected to disciplinary action: characteristics and risk factors.
AB  - OBJECTIVE To establish whether there are any characteristics of pharmacists that
      predict their likelihood of being subjected to disciplinary action. METHODS  The
      setting was the Royal Pharmaceutical Society of Great Britain's Disciplinary
      Committee. One hundred and seventeen pharmacists, all of whom had been referred
      to the Disciplinary Committee, were matched with a quota sample of 580
      pharmacists who had not been subjected to disciplinary action but that matched
      the disciplined pharmacists on a set of demographic factors (gender, country of
      residence, year of registration). Frequency analysis and regression analysis were
      used to compare the two groups of pharmacists in terms of sector of work,
      ethnicity, age and country of training. Descriptive statistics were also obtained
      from the disciplined pharmacists to further explore characteristics of
      disciplinary cases and those pharmacists who undergo them. KEY FINDINGS  While a
      number of characteristics appeared to increase the likelihood of a pharmacist
      being referred to the disciplinary committee, only one of these - working in a
      community pharmacy - was statistically significant. Professional misconduct
      accounted for a greater proportion of referrals than did clinical malpractice,
      and approximately one-fifth of pharmacists who went before the Disciplinary
      Committee had previously been disciplined by the Society. CONCLUSIONS  This study
      provides initial evidence of pharmacist characteristics that are associated with
      an increased risk of being disciplined, based upon the data currently available.
      It is recommended that follow-up work is carried out using a more extensive
      dataset in order to confirm the statistical trends identified here.

PMID- 21899619
TI  - Assessment of levels of moral reasoning in pharmacy students at different stages
      of the undergraduate curriculum.
AB  - OBJECTIVES  The principal aim of this study was to demonstrate the maturation of
      moral reasoning among pharmacy students as they progress through a 4-year degree
      programme at a school of pharmacy in the UK. METHODS  The moral reasoning of 332
      students from across all 4 years of the Master of Pharmacy (M Pharm) degree,
      together with 13 faculty members, was assessed using Rest's Defining Issues Test
      over a 1-week period. KEY FINDINGS  The results demonstrate clear increase moral
      reasoning scores through all years of study and on into membership of the
      faculty. This trend was highly significant (t = 7.09; df = 1; P < 0.001). The
      coefficient of variability (R(2) ) was calculated as 0.92 using linear least
      squares regression. There was a wide range of moral reasoning scores at each
      educational level: the top 18% of the Level 1 cohort achieved higher scores than
      the bottom 11% of faculty. CONCLUSIONS  The students at a school of pharmacy at a
      UK university experienced significant moral growth throughout the course of their
      studies. A further, longitudinal study of the cohort, which attempts to correlate
      the moral development with age, sex, level of education and mode of delivery of
      moral education is warranted.

PMID- 21899620
TI  - Using probability modelling and genetic parentage assignment to test the role of
      local mate availability in mating system variation.
AB  - The formal testing of mating system theories with empirical data is important for
      evaluating the relative importance of different processes in shaping mating
      systems in wild populations. Here, we present a generally applicable probability
      modelling framework to test the role of local mate availability in determining a
      population's level of genetic monogamy. We provide a significance test for
      detecting departures in observed mating patterns from model expectations based on
      mate availability alone, allowing the presence and direction of behavioural
      effects to be inferred. The assessment of mate availability can be flexible and
      in this study it was based on population density, sex ratio and spatial
      arrangement. This approach provides a useful tool for (1) isolating the effect of
      mate availability in variable mating systems and (2) in combination with genetic
      parentage analyses, gaining insights into the nature of mating behaviours in
      elusive species. To illustrate this modelling approach, we have applied it to
      investigate the variable mating system of the mountain brushtail possum
      (Trichosurus cunninghami) and compared the model expectations with the outcomes
      of genetic parentage analysis over an 18-year study. The observed level of
      monogamy was higher than predicted under the model. Thus, behavioural traits,
      such as mate guarding or selective mate choice, may increase the population level
      of monogamy. We show that combining genetic parentage data with probability
      modelling can facilitate an improved understanding of the complex interactions
      between behavioural adaptations and demographic dynamics in driving mating system
      variation.

PMID- 21899621
TI  - Recent long-distance transgene flow into wild populations conforms to historical
      patterns of gene flow in cotton (Gossypium hirsutum) at its centre of origin.
AB  - Over 95% of the currently cultivated cotton was domesticated from Gossypium
      hirsutum, which originated and diversified in Mexico. Demographic and genetic
      studies of this species at its centre of origin and diversification are lacking,
      although they are critical for cotton conservation and breeding. We investigated
      the actual and potential distribution of wild cotton populations, as well as the
      contribution of historical and recent gene flow in shaping cotton genetic
      diversity and structure. We evaluated historical gene flow using chloroplast
      microsatellites and recent gene flow through the assessment of transgene presence
      in wild cotton populations, exploiting the fact that genetically modified cotton
      has been planted in the North of Mexico since 1996. Assessment of geographic
      structure through Bayesian spatial analysis, BAPS and Genetic Algorithm for Rule
      set Production (GARP), suggests that G. hirsutum seems to conform to a
      metapopulation scheme, with eight distinct metapopulations. Despite evidence for
      long-distance gene flow, genetic variation among the metapopulations of G.
      hirsutum is high (He = 0.894 +/- 0.01). We identified 46 different haplotypes,
      78% of which are unique to a particular metapopulation, in contrast to a single
      haplotype detected in cotton cultivars. Recent gene flow was also detected (m =
      66/270 = 0.24), with four out of eight metapopulations having transgenes. We
      discuss the implications of the data presented here with respect to the
      conservation and future breeding of cotton populations and genetic diversity at
      its centre of crop origin.

PMID- 21899622
TI  - Opportunities and challenges facing the future global nursing and midwifery
      workforce.

PMID- 21899623
TI  - Assessing the relationships between nurse working conditions and patient
      outcomes: systematic literature review.
AB  - AIM: The purpose of the study was to systematically evaluate nurse working
      conditions and to review the literature dealing with their association with
      patient outcomes. BACKGROUND: Improving nurse working conditions is essential to
      address nursing shortages. Although general reviews of the literature support the
      positive link between working conditions and patient outcomes, definitive
      evidence has been lacking. EVALUATION: A search of six electronic bibliographic
      databases was conducted for the primary research published in English, from
      January 2000 to October 2009. KEY ISSUES: The concepts of working conditions were
      categorized into 10 groups of working conditions. A total of 69 relationships
      between working conditions and patient outcomes were examined. CONCLUSIONS:
      Increased attention has been drawn to nurse working conditions resulting from
      nursing shortages. The findings of this review suggested that the evidence
      supporting positive relationships between working conditions and patient outcomes
      is inconclusive. Further studies of a longitudinal and interventional nature in
      various settings are needed to advance knowledge of the complex contextual and
      multivariate influences among nurse working conditions and patient outcomes.
      IMPLICATIONS FOR NURSING MANAGEMENT: Efforts to improve working conditions should
      be made in various health-care work settings to ensure patient safety and improve
      patient quality of outcomes.

PMID- 21899624
TI  - The relationship between nurses' stress and nurse staffing factors in a hospital
      setting.
AB  - AIM: The present study objective was to examine the relationships between nurses'
      stress and nurse staffing in a hospital setting. BACKGROUND: Nurses have many job
      related stressors. There is a lack of research exploring the relationship between
      job stressors to staffing and day of week worked. METHODS: The sample consisted
      of registered nurses (RNs) (N = 197) providing direct patient care. Data were
      collected via electronic software. Variables included demographic information,
      work setting information, Perceived Stress Scale (PSS) scores and Nursing Stress
      Scale (NSS) scores. Data analysis included descriptive statistics, correlations
      and analysis of variance. RESULTS: Among respondents, a positive correlation (r =
      0.363, P  0.05) was found between the NSS and PSS and between age and patient
      work load (i.e. number of patients the nurse cared for) (r = 0.218, P < 0.05). A
      negative correlation (r = -0.142, P < 0.05) existed between NSS and respondents'
      age. Analysis of variance showed that younger nurses had more nursing stress than
      older nurses (F(1,195) = 4.283, P < 0.05). CONCLUSIONS: Age, patient work load
      and day of the week worked are important factors affecting nurses' stress levels.
      IMPLICATIONS FOR NURSING MANAGEMEN: Nurse managers should consider scheduling as
      a potential stressor for nurses.

PMID- 21899625
TI  - Role stress amongst nurses at the workplace: concept analysis.
AB  - AIM: The present study explicates the concept of role stress amongst nurses
      through an analysis adopted from Walker and Avant; Strategies for Theory
      Construction in Nursing, 4th edn, Prentice Hall, New Jersey, NY. BACKGROUND: Role
      stress has become a significant problem amongst nurses and has created much
      distress leading to burnout among many in the nursing profession. It is
      significant to analyse the concept of role stress and its relative attributes and
      consequences, in order to recognize the necessary antecedents needed to create
      better conditions for nurses at the workplace. EVALUATION: A modified method
      developed by Walker and Avant was used for this concept analysis. KEY ISSUES: A
      model representing the concept of role stress was developed through careful
      consideration of the attributes, consequences, antecedents and empirical
      referents of role stress. CONCLUSION: The concept analysis of role stress among
      nurses at the workplace recognized the vulnerability of the nursing discipline
      towards burnout and distress in general. IMPLICATIONS FOR NURSING MANAGEMENT: It
      is critical to be aware of the current state of health care and note the
      increased workload created for nurses. Nurses are at a greater vulnerability for
      role stress, making it imperative for health care organizations to critically
      evaluate and establish preventative measures for the concept of role stress.

PMID- 21899626
TI  - Working life and stress symptoms among caregivers in elderly care with formal and
      no formal competence.
AB  - AIM: The aim of the present study was to describe and compare caregivers with
      formal and no formal competence on job satisfaction, psychosomatic health,
      structural and psychological empowerment and perceptions of care quality. A
      further aim was to study relationships among study variables. METHODS: A
      convenience sample of 572 caregivers in elderly care participated. RESULTS:
      Caregivers with no formal competence perceived higher workload, more
      communication obstacles, less competence, poorer sleep and more stress symptoms
      than did their colleagues. Linear regression analyses revealed that the factor
      self-determination was an explanatory variable of stress levels among caregivers
      with no formal competence, and self-determination and impact among caregivers
      with formal competence. Linear regression analysis revealed that different
      dimensions in structural and psychological empowerment explained the variance in
      staff job satisfaction, perceived stress symptoms and quality of care.
      CONCLUSIONS: No formal competence seems to be a risk factor for psychosomatic
      health problems. IMPLICATIONS FOR NURSING MANAGEMENT: Managers need to have a
      strategic plan for how to create a working environment for caregivers with no
      formal competence. Caregivers' self-determination seems to be important for
      stress symptoms. Meaning, self-determination, impact and opportunities appear to
      be important for job satisfaction and competence, opportunities, resources and
      formal power for quality of care.

PMID- 21899627
TI  - Bullying and employee turnover among healthcare workers: a three-wave prospective
      study.
AB  - AIM: To investigate the risk of turnover among targets of bullying at work.
      BACKGROUND: Exposure to bullying seems to leave targets with intentions to leave
      their workplaces. However, it is uncertain to what extent they actually leave.
      METHOD: Data were collected by questionnaires in a three-wave study among Danish
      healthcare workers at the time of graduation (T1 ), 1 (T2 ) and 2 years (T3 )
      later. We followed 2154 respondents who participated in all three waves. RESULTS:
      The first year after graduation, 9.2% reported being bullied at work, 1.8%
      frequently. Follow-up analyses showed a strong relationship between exposure to
      bullying at T2 and turnover at T3 [odds ratio (OR) for frequently bullied = 3.1].
      The inclusion of push factors such as low social support and low sense of
      community, intention to leave and ill health did not change the relation between
      bullying and turnover significantly. Three reasons for quitting stood out among
      reasons given by the bullied respondents: poor leadership, being exposed to
      negative behaviour and health problems. CONCLUSION: Bullying may be costly to an
      organization in terms of staff turnover and subsequent recruitment and training
      of replacements. IMPACT FOR NURSING MANAGEMENT: Managers should regularly monitor
      the psychosocial work environment. To prevent bullying local policies and
      procedures should be developed, implemented and evaluated.

PMID- 21899628
TI  - One-year prospective study on the effect of workplace bullying on long-term
      sickness absence.
AB  - AIMS: To examine the effect of workplace bullying on long-term sickness absence
      using a prospective design. BACKGROUND: Although bullying has been identified as
      a serious problem in the health care sector, little attention has been given to
      the possible effect of workplace bullying on long-term sickness absence and its
      implications. METHODS: The sample consisted of 9949 employees (78.1% response
      rate) working in the elderly-care sector in 36 Danish municipalities. Long-term
      sickness absence was measured by linking a survey on work and health to the
      national register on social transfer payments. RESULTS: Among the 1171 employees
      that were bullied at work in the past 12 months, 1.8% were frequently bullied and
      7.3% were occasionally bullied. The risk of long-term sickness absence was higher
      for those frequently bullied even after adjusting for psychosocial work
      characteristics [rate ratio (RR) = 1.92, confidence interval (CI): 1.29-2.84; P <
      0.05]. CONCLUSION: This is the first prospective study that explored the effect
      of both frequent and occasional bullying on long-term sickness absence among
      health care employees. The effect of frequent bullying on long-term sickness
      absence was independent of the psychosocial work characteristics. IMPLICATIONS
      FOR NURSING MANAGEMENT: Workplace bullying might impact negatively the quality of
      care and patients safety.

PMID- 21899629
TI  - Occupational stress, job satisfaction and job performance among hospital nurses
      in Kampala, Uganda.
AB  - AIMS: To assess levels of occupational stress, job satisfaction and job
      performance among hospital nurses in Kampala, Uganda; and how they are influenced
      by work and personal characteristics. BACKGROUND: Occupational stress is reported
      to affect job satisfaction and job performance among nurses, thus compromising
      nursing care and placing patients' lives at risk. Although these factors have
      been studied extensively in the US and Europe, there was a need to explore them
      from the Ugandan perspective. METHODS: A correlational study was conducted with
      333 nurses from four hospitals in Kampala, Uganda. A questionnaire measuring
      occupational stress, job satisfaction and job performance was used. Data were
      analysed using descriptive statistics and anova. RESULTS: There were significant
      differences in levels of occupational stress, job satisfaction and job
      performance between public and private not-for-profit hospitals, nursing
      experience and number of children. CONCLUSIONS: Organizational differences
      between public and private not-for-profit hospitals influence the study
      variables. IMPLICATIONS FOR NURSING MANAGEMENT: On-the-job training for nurse
      managers in human resource management to increase understanding and advocacy for
      organizational support policies was recommended. Research to identify
      organizational, family or social factors which contribute to reduction of
      perceived occupational stress and increase job satisfaction and job performance
      was recommended.

PMID- 21899630
TI  - Relations among depression, self-efficacy and optimism in a sample of nurses in
      Taiwan.
AB  - AIMS: The present study investigated the level of depression among hospital
      nurses, to examine personality contributions to depression and to offer managers
      relevant organizational strategies to reduce levels of depression. BACKGROUND:
      The World Health Organization's Global Burden of Disease Study estimates that
      major depression is the leading cause of disability among women in the world
      today. It is surprising that there is a relative dearth of research investigating
      depression among nursing staff. METHOD: A cross-sectional survey of 314 staff
      nurses in a general hospital in Taiwan. Participants completed a set of
      questionnaires and a demographic information form. A number of statistical
      methods were used including descriptive statistics, product-moment correlations
      and multiple regression analysis. RESULTS: In all, 52.5% of nurses reported mild
      to-moderate depressive symptoms. Self-efficacy and optimism were significant
      buffers against depression. CONCLUSIONS: The results of the present study confirm
      the importance of self-efficacy and optimism. Nurses with positive evaluation and
      expectation towards their self and others tend to report lower depression levels.
      IMPLICATIONS FOR NURSING MANAGEMENT: The results of the present study indicate
      that there is an immediate need to pay further attention to nurses' depression
      issues. It is therefore suggested that Nursing Managers take an empowering
      approach to strengthen nurses' self-efficacy and optimism levels to prevent
      depression in this profession.

PMID- 21899631
TI  - Changing the model of care delivery: nurses' perceptions of job satisfaction and
      care effectiveness.
AB  - AIM: To examine nurses' perceptions of job satisfaction, empowerment, and care
      effectiveness following a change from team to a modified total patient care (TPC)
      delivery model. BACKGROUND: Empirical data related to TPC is limited and
      inconclusive. Similarly, evidence demonstrating nurses' experience with change
      and restructuring is limited. METHOD: A mixed method, longitudinal, descriptive
      design was used. Registered nurses and licenced practical nurses in two acute
      care nursing units completed quantitative and qualitative surveys. Lewin's change
      theory provided the framework for the study. RESULTS: No significant change in
      job satisfaction was observed; however, it was less than optimal at all three
      time-periods. Nurses were committed to their jobs but relatively dissatisfied
      with their input into the goals and processes of the organization. Client care
      was perceived to be more effective under TPC. CONCLUSION: Job satisfaction
      remained consistent following the transition to TPC. However, nurses perceived
      that client care within the modified TPC model was more effective than in the
      previous model. IMPLICATIONS FOR NURSING MANAGEMENT: Nursing administration must
      work collaboratively with nurses to improve processes in nursing practice that
      could enhance nurses' job satisfaction and improve client care delivery.

PMID- 21899632
TI  - A review of nursing workforce policies in five European countries: Denmark,
      Finland, Ireland, Portugal and United Kingdom*/England.
AB  - AIM: Review nursing workforce policies in five European countries: Denmark,
      Finland, Ireland, Portugal and the United Kingdom*. BACKGROUND: Imbalances in
      registered nurse (RN) supply and demand is a global, significant and recurring
      issue that impacts on healthcare systems, organizations, staff and patients.
      METHOD: Policy Review using resources located by a systematic search of relevant
      healthcare databases and policies in Danish, English, Finnish and Portuguese over
      the time period 2003-2007. Content analysis was used to identify themes and
      compare policies. RESULTS: Common nursing workforce policy themes were identified
      across the five countries: (1) improving retention through effective human
      resource management, improving the practice environment and nurses' working lives
      and (2) improving recruitment through attracting more new recruits and RNs back
      to practice, and international recruitment. The present study also identified
      methodological issues relating to data quality and quantity. Lack of an agreed
      definition and standardized measures of nursing need and shortage makes
      comparison and evaluation of policy effectiveness and impact difficult.
      IMPLICATIONS FOR NURSING MANAGEMENT: Healthcare systems and organizations need to
      identify and implement effective policies that promote the retention of RNs in
      the workforce, or risk threats to healthcare system sustainability, as well as
      patient care quality and safety.

PMID- 21899633
TI  - The management of poor performance in nursing and midwifery: a case for concern.
AB  - AIM(S): To examine the evidence of how poorly performing nurses and midwives are
      managed in the UK National Health Service (NHS). BACKGROUND: Nurses and midwives
      form the largest clinical group in the NHS. There is little evidence, however,
      about poor performance and its management in nursing and midwifery literature.
      METHOD(S): The present study comprised a literature search, analysis of recent
      Nursing and Midwifery Council (NMC) data and observation at NMC fitness to
      practice hearings. RESULT: Nurses and midwives are the clinical groups most
      likely to be suspended in the NHS; Trusts do not report data on suspensions
      therefore no data exist on numbers, reasons for suspensions, managerial
      processes, gender, area of work, or ethnicity of those suspended; the few major
      research projects identify variable management practices, the significant
      financial cost to the NHS and the personal cost to those suspended; there is
      evidence that inexperienced, poorly trained, or poorly supported managers use
      suspension inappropriately. Our observation supported this. CONCLUSION(S): There
      is a need for robust data gathering and research in the field of NHS managerial
      practice. IMPLICATIONS FOR NURSING MANAGEMENT: Managers should refrain from
      adopting punitive forms of performance management. Frontline staff and management
      need better training and support for dealing with poor performance.

PMID- 21899634
TI  - Implementation of a multi-professional standardized care plan in electronic
      health records for the care of stroke patients.
AB  - AIMS: To compare staff opinions about standardized care plans and self-reported
      habits with regard to documentation, and their perceived knowledge about the
      evidence-based guidelines in stroke care before and after implementation of an
      evidence-based-standardized care plan (EB-SCP) and quality standard for stroke
      care. The aim was also to describe staff opinions about, and their use of, the
      implemented EB-SCP. BACKGROUND: To facilitate evidence-based practice (EBP), a
      multi-professional EB-SCP and quality standard for stroke care was implemented in
      the electronic health record (EHR). METHOD: Quantitative, descriptive and
      comparative, based on questionnaires completed before and after implementation.
      RESULTS: Perceived knowledge about evidence-based guidelines in stroke care
      increased after implementation of the EB-SCP. The majority agreed that the EB-SCP
      is useful and facilitates their work. There was no change between before and
      after implementation with regard to opinions about standardized care plans, self
      reported documentation habits or time spent on documentation. CONCLUSIONS: An
      evidence-based SCP seems to be useful in patient care and improves perceived
      knowledge about evidence-based guidelines in stroke care. IMPLICATIONS FOR
      NURSING MANAGEMENT: For nursing managers, introduction of evidence-based SCP in
      the EHR may improve the prerequisites for promoting high-quality EBP in multi
      professional care.

PMID- 21899635
TI  - Nurse consultants 10 years on: an insight to the role for nurse managers.
AB  - AIMS: To evaluate the Non-Medical Consultant role in the North West of England.
      The objective was to identify the current number of Non-Medical Consultants, what
      they do and the impact of the role in practice. BACKGROUND: The Non-Medical
      Consultant role for nursing and midwifery was introduced in the UK in 2000 to
      provide better outcomes for patients by improving service and quality;
      strengthening clinical leadership; and providing a new career opportunity to help
      retain experienced and expert professionals in practice. DESIGN: A combined
      qualitative and quantitative design was adopted. This included desktop review of
      previous studies, a survey questionnaire to current consultants, focus group
      meetings with Non-Medical Consultants, sponsors and champions. RESULTS: The role
      is effective, flexible, responsive and outward facing both internal to the
      organization and externally on a local, regional and national basis. A key
      challenge for the Non-Medical Consultants was organizational understanding of the
      role. The small size of the Non-Medical Consultant workforce can limit individual
      organizations experience of establishing and supporting the role. CONCLUSION:
      Effective Non-Medical Consultants lead, drive and support quality improvement,
      increased productivity and service effectiveness. Other impacts include sharing
      and promoting best practice with colleagues, income generation and financial
      savings through service redesign and/or staff skill mix changes. IMPLICATIONS FOR
      NURSING MANAGEMENT: Managerial issues identified may assist Nurse Managers
      seeking to introduce new consultant roles and/or support, and retain existing
      consultants to reach their full potential.

PMID- 21899636
TI  - Higher in vitro resistance to oxidative stress in extra-pair offspring.
AB  - Oxidative stress is considered to act as a universal physiological constraint in
      life-history evolution of animals. This should be of interest for extra-pair
      paternity behaviour, and we tested here the prediction that offspring arising
      from extra-pair matings of female great tits show higher resistance to oxidative
      stress than within-pair offspring. Resistance to oxidative stress, measured as
      the whole blood resistance to a controlled free-radical attack, was significantly
      higher for extra-pair offspring as predicted although these were not heavier or
      in better body condition than within-pair offspring. Since resistance to
      oxidative stress has been suggested to enhance survival and reproductive rates,
      extra-pair offspring with superior resistance to oxidative stress, be it through
      maternal effects or paternal inheritance, may achieve higher fitness and thus
      provide significant indirect fitness benefits to their mothers. In addition,
      because oxidative stress affects colour signals and sperm traits, females may
      also gain fitness benefits by producing sons that are more attractive (sexy-sons
      hypothesis) and have sperm of superior quality (sexy-sperm hypothesis).
      Heritability of resistance to oxidative stress as well as maternal effects may
      both act as proximate mechanisms for the observed result. Disentangling these two
      mechanisms would require an experimental approach. Future long-term studies
      should also aim at experimentally testing whether higher resistance to oxidative
      stress of EP nestlings indeed translates into fitness benefits to females.

PMID- 21899637
TI  - The role of mobility for the emergence of diversity in victim-exploiter systems.
AB  - Theoretical and empirical studies indicate that exploitation is a possible driver
      of exploiter and victim diversification. However, there are many factors which
      could promote and limit this diversification process. Using a spatially explicit
      individual-based model, where an exploiter's success depends on matching between
      its own and a victim's continuous trait, we simulate local communities of victims
      and exploiters. We investigate how exploiter mobility (searching ability and
      movement strategies) can influence diversification of victims. We find that if
      victim traits are under intermediate intensity of stabilizing selection,
      disruptive selection exerted by exploiters can indeed lead to diversification in
      victim population and the victim trait distribution can split into two or more
      groups. Searching ability and movement strategy of exploiters (local vs. global
      movement) play a role in determining the number of victim trait groups emerging.
      Moreover, they affect the proportion of infected victims and the formation of
      spatial patterns in the victim trait distribution. In addition, with a high
      searching ability, exploiters with global movement drive victims to be more
      diverse than exploiters with local movement.

PMID- 21899638
TI  - Diversification in temporally heterogeneous environments: effect of the grain in
      experimental bacterial populations.
AB  - Although theory established the necessary conditions for diversification in
      temporally heterogeneous environments, empirical evidence remains controversial.
      One possible explanation is the difficulty of designing experiments including the
      relevant range of temporal grains and the appropriate environmental trade-offs.
      Here, we experimentally explore the impact of the grain on the diversification of
      the bacterium Pseudomonas fluorescens SBW25 in a temporally fluctuating
      environment by including 20 different pairs of environments and four temporal
      grains. In general, higher levels of diversity were observed at intermediate
      temporal grains. This resulted in part from the enhanced capacity of disruptive
      selection to generate negative genotypic correlations in performance at
      intermediate grains. However, the evolution of reciprocal specialization was an
      uncommon outcome. Although the temporal heterogeneity is in theory less powerful
      than the spatial heterogeneity to generate and maintain the diversity, our
      results show that diversification under temporal heterogeneity is possible
      provided appropriate environmental grains.

PMID- 21899639
TI  - Monitoring for and preventing the long-term sequelae of bariatric surgery.
AB  - PURPOSE: To present a case study of a patient with multiple comorbid diseases who
      undergoes bariatric surgery. DATA SOURCES: Recent clinical and research articles,
      bariatric professional society guidelines, and government sources were culled to
      provide recommendations for the care of the person who chooses bariatric surgery
      as the treatment for the comorbid conditions of obesity, type 2 diabetes,
      obstructive sleep apnea, hypertension, and hyperlipidemia. CONCLUSIONS: As
      surgical management of obesity becomes more prevalent in an attempt to improve
      health-related quality of life, reduce mortality, and address the comorbidities
      that are prevalent in this population, nurse practitioners (NPs) need to
      understand what long-term management these patients will require. IMPLICATIONS
      FOR PRACTICE: NPs are primary care providers for patients with chronic diseases.
      It is likely that they will make referrals for this surgery and follow the
      patient after the procedure at some point. Knowledge of what the procedures
      involve, what changes to expect in the comorbid conditions, and what long-term
      monitoring and treatment should take place in the care of these patients will
      provide these patients with optimal care.

PMID- 21899640
TI  - Guidance of pharmacotherapy in a complex psychiatric case by CYP450 DNA typing.
AB  - PURPOSE: To illustrate the utility of CYP450 genotyping to guide clinical
      psychopharmacological treatment decisions and minimize or avoid harmful and
      costly adverse drug reactions (ADRs). DATA SOURCES: DNA was extracted from a
      whole blood sample from the case study subject and tested for CYP450 gene
      polymorphisms in the CLIA certified Laboratory of Personalized Health at Genomas,
      Inc. Clinical data were obtained from patient records and clinician observations.
      CONCLUSIONS: We present a case in which the ascertainment of multiple CYP450
      isoenzyme deficiencies resulted in a dramatic change in psychotropic treatment
      approach. Shortly after making these adjustments, the patient saw a significant
      improvement in most of her debilitating psychiatric symptoms. IMPLICATIONS FOR
      PRACTICE: In complex cases, CYP450 DNA testing can guide pharmacotherapy by
      exposing innate hepatic metabolic deficiencies as a result of DNA polymorphism.
      In such cases, clinicians can favor treatments that target functional isoenzyme
      pathways rather than deficient or null pathways thus leading to decreased risk of
      ADRs and improved patient response.

PMID- 21899641
TI  - Management of amyotrophic lateral sclerosis (ALS) by the family nurse
      practitioner: a timeline for anticipated referrals.
AB  - PURPOSE: This article reviews characteristics of amyotrophic lateral sclerosis
      (ALS) and appropriate timing of referrals by the nurse practitioner (NP). DATA
      SOURCES: Selected research and clinical articles. CONCLUSION: Management of
      patients with ALS by the NP requires anticipation of needed referrals based on
      symptom assessment and knowledge of the common timeline of ALS progression. Close
      collaboration with specialists such as neurologists, pulmonologists, and a
      palliative care team provides patients and families with much needed support and
      improves outcomes. IMPLICATIONS FOR PRACTICE: Anticipating and initiating
      appropriate and timely referrals for patients with ALS may improve quality of
      life for patients with this devastating condition.

PMID- 21899642
TI  - Genetic disparities in the development of type 2 diabetes among African
      Americans.
AB  - PURPOSE: The purpose of this paper is to discover whether biological and genetic
      differences play an important role in the pathogenesis of developing type 2
      diabetes in the African-American population DATA SOURCES: Review of original
      studies and meta-analyses from Medline, PubMed, CINAHL, Scopus CONCLUSION: It is
      now well established that the development of type 2 diabetes results from the
      interaction between the individuals' biological and genetic makeup and their
      environment. Even though some genetic variants have been found, the full genetic
      landscape of type 2 diabetes, especially among African-Americans, is not yet
      discovered. Further researches or studies on pathophysiology and genetic
      susceptibility to diabetes may suggest new therapeutic targets for the treatment
      and prevention of insulin resistance. IMPLICATIONS FOR PRACTICE: Considering
      genetics as a potential cause of type 2 diabetes may suggest new therapeutic
      targets for the treatment and prevention, and new detecting tools for the
      undiagnosed patients. Nurse practitioners may gain a better understanding of the
      particular genetic defect influencing individual health and create the
      appropriate care plan to achieve an optimal health outcome for a patient.

PMID- 21899643
TI  - Interpreting clinical trial results for moderate-to-severe rheumatoid arthritis:
      practical applications for rheumatology healthcare providers.
AB  - PURPOSE: To provide a general overview of clinical trials and more specifically
      define measurements common to rheumatoid arthritis clinical trials for the
      purpose of providing a foundation for rheumatology healthcare providers to
      translate clinical trial findings into their clinical practice and enhance their
      patient education discussions. DATA SOURCES: English-language publications cited
      in the MEDLINE database were used to develop the content of this review article.
      CONCLUSIONS: The role of rheumatology healthcare providers has evolved to include
      numerous vital functions, such as expanding communication between specialists and
      primary care providers, patient education and counseling, assistance with coping
      strategies, monitoring response to therapy, and administration of therapy.
      Education regarding clinical trial design, rationale, and discussion of endpoints
      has not been strongly emphasized for rheumatology healthcare providers who are
      increasingly introduced to novel agents and need to assimilate findings from
      clinical trials into daily practice. IMPLICATIONS FOR PRACTICE: Familiarity with
      the basics of clinical trial design and efficacy endpoints of new rheumatoid
      arthritis therapeutics, translation and application of that knowledge into daily
      practice, and the ability to explain this information with patients will further
      enhance the ability of the rheumatology healthcare provider to optimize care for
      their patients with rheumatoid arthritis.

PMID- 21899644
TI  - The feasibility and effectiveness of emergency department based hypertension
      screening: a systematic review.
AB  - PURPOSE: Hypertension is a highly prevalent risk factor for cardiovascular
      disease, and its early identification and management results in reductions in
      morbidity and mortality. Our objectives were to: (1) determine the extent to
      which the emergency department (ED) has been used to screen patients for
      undiagnosed hypertension; (2) estimate the incidence of undiagnosed hypertension
      in the ED population; (3) identify and describe the programs for ED hypertension
      screening; and (4) determine the feasibility of ED-based hypertension screening
      programs and the requirements for further study. DATA SOURCES: An online search
      of databases (i.e., OVID Search, CINAHL, Scopus, Web of Science), unpublished
      sources (i.e., ProQuest Dissertation & Theses and Papers First), and grey
      literature (i.e., OpenSIGLE and the New York Academy of Grey Literature) was
      conducted. A manual search of the reference lists of relevant studies was also
      completed. CONCLUSION: Hypertension screening in the ED is feasible. Individuals
      with elevated blood pressure (BP) in the ED should be referred for follow-up.
      Further study is needed to develop an ED screening tool that is predictive of
      persistently elevated BP in undiagnosed individuals. IMPLICATIONS FOR PRACTICE:
      Nurse practitioners in the ED should identify patients with elevated BP, provide
      hypertension education, and ensure appropriate intervention and referral.

PMID- 21899645
TI  - Perceived barriers to immunizations as identified by Latino mothers.
AB  - PURPOSE: Identify low-income Latino mothers' perceived barriers to immunizations.
      DATA SOURCES: A 1-month survey was conducted in a Southern California, low-income
      primary care clinic. Mothers of Latino children aged 2 months to 18 years were
      surveyed in Spanish using a 52-question immunization survey. CONCLUSIONS: Latino
      mothers' perception of immunizations and knowledge of up-to-date status greatly
      influenced their children's immunization status. In addition, Latino children had
      lower immunization rates and encountered more barriers to immunizations than
      children in other population groups despite government efforts to provide
      vaccines to healthcare providers at no cost to assist low-income children. Most
      mothers (92%) believed their children were up-to-date on immunizations; however,
      immunization records documented that 42% of the children were current based on
      age. The most common barriers reported were that the child was sick at the time
      of the visit (51%) and/or transportation problems (39%). IMPLICATIONS FOR
      PRACTICE: When working with low-income, uninsured Latinos, nurse practitioners
      and other healthcare professionals with low immunization rates in their clinic
      must assess the barriers to immunization and implement an action plan.

PMID- 21899646
TI  - Commitment strength in motivational interviewing and movement in exercise stage
      of change in women.
AB  - PURPOSE: Motivational interviewing (MI) increasingly is used in behavior change
      counseling. We explored whether commitment verbalized in an initial MI session
      predicted subsequent physical activity behavior. DATA SOURCES: As part of a 12
      week walking program targeted at rural women, an initial MI session was held that
      was audio-recorded. We measured commitment strength during this MI session, stage
      of change (SOC) pre- and postintervention, and minutes of physical activity
      performed during the 12-week intervention for the 20 women in the intervention.
      CONCLUSIONS: Commitment strength was significantly correlated with SOC, and SOC
      was significantly correlated with physical activity behavior. However, commitment
      strength did not predict physical activity. Further research is needed to
      determine if commitment strength predicts subsequent physical activity.
      IMPLICATIONS FOR PRACTICE: Understanding the role of the strength of a commitment
      statement made during an initial MI session could assist the APN in directing
      follow-up MI sessions. This information could be useful in improving the cost
      effectiveness and efficiency of conducting MI.

PMID- 21899647
TI  - Reversible vasoconstriction syndrome with bilateral basal ganglia hemorrhages.
AB  - Reversible cerebral vasoconstriction syndrome (RCVS) is an increasingly
      recognized acute cerebrovascular condition that may produce myriad transient and
      sustained neurologic deficits as well as a host of radiologic features. We report
      the case of a woman with RCVS and a severe clinical syndrome with bilateral basal
      ganglia hemorrhages, cerebral infarctions, and marked vascular abnormalities. The
      patient made a near complete clinical recovery, representing an extreme and
      illustrative form of RCVS.

PMID- 21899648
TI  - Breast conservation therapy in the 21st century.

PMID- 21899649
TI  - Adjuvant chemotherapy with TAC (docetaxel, doxorubicin, and cyclophosphamide) in
      patients with breast cancer--incidence of neutropenic fever outside clinical
      trials.

PMID- 21899651
TI  - Primary radiotherapy with or without chemotherapy in non-metastatic esophageal
      squamous cell carcinoma: a retrospective study.
AB  - The purpose of this study was to report the outcome of radio(chemo)therapy in the
      curative management of esophageal squamous cell carcinoma (ESCC). We
      retrospectively analyzed 163 patients with T1-T4, N0-1, M0 ESCC who were treated
      between January 1988 and December 2006 at the Technische Universitat Munchen. One
      hundred sixty patients were inoperable due to a poor performance status,
      comorbidities or locally advanced unresectable disease. External beam radiation
      therapy (EBRT) was performed with (n= 146) or without (n= 17) systemic
      chemotherapy. Fifty-four patients received an additional boost with intraluminal
      brachytherapy (IBT). Surviving patients were followed for a median of 72 months
      (range 10-173 months). The estimated overall survival (OS) at 2 and 5 years was
      27 +/- 4% and 11 +/- 3%, respectively. Loco-regional recurrence at the primary
      site was observed in 29% of patients (n= 47). The recurrence-free survival (RFS)
      at 2 and 5 years was 24 +/- 3% and 9 +/- 2%, respectively. In multivariate
      analyses, the ECOG performance status (P= 0.004), 3D conformal (vs conventional)
      radiotherapy (P= 0.031) and continuous standard fractionation (vs split-course
      radiotherapy, P= 0.048) were associated with a better OS. Simultaneous
      chemotherapy (P= 0.49) or IBT (P= 0.31) had no significant impact on survival.
      Outcome for patients with ESCC is poor. Despite the very unfavorable patient
      selection (poor performance status, high rate of comorbidities, and advanced
      disease), long-term survival with radio(chemo)therapy was achieved in about 10%
      of patients. The introduction of modern treatment techniques/modalities (3D
      conformal planning/ continuous standard fractionation) might be associated with
      better outcomes.

PMID- 21899652
TI  - Robot-assisted minimally invasive esophagectomy is equivalent to thoracoscopic
      minimally invasive esophagectomy.
AB  - The use of the surgical robot has been increasing in thoracic surgery. Its three
      dimensional view and instruments with surgical wrists may provide advantages over
      traditional thoracoscopic techniques. Our initial experience with thoracoscopic
      robot-assisted minimally invasive esophagectomy (RAMIE) for esophageal cancer was
      compared with our traditional thoracoscopic minimally invasive esophagectomy
      (MIE) approach for esophageal cancer. A retrospective review of a prospective
      database was performed. From July 2008 to October 2009, 43 patients underwent MIE
      resection. Patients who had benign disease and intrathoracic anastomosis were
      excluded. Results are presented as mean +/- SD. Significance was set as P < 0.05.
      Eleven patients who underwent RAMIE and 26 who underwent MIE were included in the
      cohort. No differences in age, sex, race, body mass index, or preoperative
      radiotherapy or chemotherapy between the groups were observed. No significant
      differences in operative time, blood loss, number of resected lymph nodes,
      postoperative complications, days of mechanical ventilation, length of intensive
      care unit stay, or length of hospital stay were also observed. In this short-term
      study, RAMIE was found to be equivalent to thoracoscopic MIE and did not offer
      clear advantages.

PMID- 21899653
TI  - Recombinant vascular endothelial growth factor165 gene therapy improves
      anastomotic healing in an animal model of ischemic esophagogastrostomy.
AB  - Proper anastomotic healing is dependent upon many factors including adequate
      blood flow to healing tissue. The aim of this study was to investigate the impact
      of vascular endothelial growth factor (VEGF(165)) transfection on anastomotic
      healing in an ischemic gastrointestinal anastomosis model. Utilizing an
      established opossum model of esophagogastrectomy followed by esophageal-gastric
      anastomosis, the gastric fundus was transfected with recombinant human vascular
      endothelial growth factor via direct injection of a plasmid-based nonviral
      delivery system. Twenty-nine animals were divided into three groups: two
      concentrations of VEGF and a control group. Outcomes included VEGF mRNA
      transcript levels, neovascularization, tissue blood flow, and anastomotic
      bursting pressure. To determine whether local injection resulted in a systemic
      effect, distant tissues were evaluated for VEGF transcript levels. Successful
      gene transfection was demonstrated by quantitative polymerase chain reaction
      analysis of anastomotic tissue, with significantly higher VEGF mRNA expression in
      treated animals compared to controls. At the gastric side of the anastomosis,
      there was significantly increased neovascularization, blood flow, and bursting
      pressure in experimental animals compared to controls. There were no differences
      in outcome measures between low- and high-dose VEGF groups; however, the high
      dose group demonstrated increased VEGF mRNA expression across the anastomosis.
      VEGF production was not increased at distant sites in treated animals. In this
      animal model, VEGF gene therapy increased VEGF transcription at a healing
      gastrointestinal anastomosis without systemic VEGF upregulation. This treatment
      led to improved healing and strength of the acutely ischemic anastomosis. These
      findings suggest that VEGF gene therapy has the potential to reduce anastomotic
      morbidity and improve surgical outcomes in a wide array of patients.

PMID- 21899654
TI  - Combined stent insertion and single high-dose brachytherapy in patients with
      advanced esophageal cancer--results of a prospective safety study.
AB  - Previous randomized studies comparing the two commonly used palliative treatments
      for incurable esophageal cancer, i.e. stent insertion and intraluminal
      brachytherapy, have revealed the pros and cons of each therapy. While stent
      treatment offers a more prompt effect, brachytherapy results in more long-lasting
      relief of dysphagia and a better health-related quality of life (HRQL) in those
      living longer. This prospective pilot study aimed to explore the feasibility and
      safety of combining these two regimes and incorporating a single high dose of
      internal radiation. Patients with newly diagnosed, incurable cancer of the
      esophagus and dysphagia were eligible for inclusion, and stent insertion followed
      by a single dose (12 Gy) of brachytherapy was performed as a two-stage procedure.
      Clinical parameters including HRQL and adverse events were registered at
      inclusion, and 1, 2, 3, 6, and 12 months later. Twelve patients (nine males) with
      a median age of 73 years (range 54-85) were included. Stent insertion followed by
      a single dose of brachytherapy was successfully performed in all but one patient
      who was treated with stent only. Relief of dysphagia was achieved in the majority
      of cases (10/11, P < 0.05), but HRQL did not improve except for dysphagia-related
      items. Only minor adverse events, including chest pain, reflux, and restenosis,
      were reported. The median survival time after inclusion was 6.6 months. Our
      conclusion is that the combination of stent insertion and single high-dose
      brachytherapy seems to be a feasible and safe palliative regime in patients with
      advanced esophageal cancer. Randomized trials comparing the efficacy of this
      strategy to stent insertion or brachytherapy alone are warranted.

PMID- 21899655
TI  - The prevalence of autoimmune disease in patients with esophageal achalasia.
AB  - Achalasia is a rare disease of the esophagus that has an unknown etiology.
      Genetic, infectious, and autoimmune mechanisms have each been proposed.
      Autoimmune diseases often occur in association with one another, either within a
      single individual or in a family. There have been separate case reports of
      patients with both achalasia and one or more autoimmune diseases, but no study
      has yet determined the prevalence of autoimmune diseases in the achalasia
      population. This paper aims to compare the prevalence of autoimmune disease in
      patients with esophageal achalasia to the general population. We retrospectively
      reviewed the charts of 193 achalasia patients who received treatment at Toronto's
      University Health Network between January 2000 and May 2010 to identify other
      autoimmune diseases and a number of control conditions. We determined the general
      population prevalence of autoimmune diseases from published epidemiological
      studies. The achalasia sample was, on average, 10-15 years older and had slightly
      more men than the control populations. Compared to the general population,
      patients with achalasia were 5.4 times more likely to have type I diabetes
      mellitus (95% confidence interval [CI] 1.5-19), 8.5 times as likely to have
      hypothyroidism (95% CI 5.0-14), 37 times as likely to have Sjogren's syndrome
      (95% CI 1.9-205), 43 times as likely to have systemic lupus erythematosus (95% CI
      12-154), and 259 times as likely to have uveitis (95% CI 13-1438). Overall,
      patients with achalasia were 3.6 times more likely to suffer from any autoimmune
      condition (95% CI 2.5-5.3). Our findings are consistent with the impression that
      achalasia's etiology has an autoimmune component. Further research is needed to
      more conclusively define achalasia as an autoimmune disease.

PMID- 21899656
TI  - Spinal blocks.
AB  - Every anesthetist should have the expertise to perform lumbar puncture that is
      the prerequisite to induce spinal anesthesia. Spinal anesthesia is easy and
      effective technique: small amount of local anesthetic injected in the lumbar
      cerebrospinal fluid provides highly effective anesthesia, analgesia, and
      sympathetic and motor block in the lower part of the body. The main limitation of
      spinal anesthesia is a variable and relatively short duration of the block with a
      single-injection of local anesthetic. With appropriate use of adjuvant or
      combining spinal anesthesia with epidural anesthesia, the analgesic action can be
      controlled in case of early recovery of initial block or in patients with
      prolonged procedures. Contraindications are rare. Bleeding disorders and any
      major dysfunction in coagulation system are rare in children, but spinal
      anesthesia should not be used in children with local infection or increased
      intracranial pressure. Children with spinal anesthesia may develop the same
      adverse effects as has been reported in adults, but in contrast to adults,
      cardiovascular deterioration is uncommon in children even with high blocks. Most
      children having surgery with spinal anesthesia need sedation, and in these cases,
      close monitoring of sufficient respiratory function and protective airway
      reflexes is necessary. Postdural puncture headache and transient neurological
      symptoms have been reported also in pediatric patients, and thus, guardians
      should be provided instructions for follow-up and contact information if symptoms
      appear or persist after discharge. Epidural blood patch is effective treatment
      for prolonged, severe headache, and nonopioid analgesic is often sufficient for
      transient neurological symptoms.

PMID- 21899657
TI  - Disease-free survival of patients after surgical resection of non-small cell lung
      carcinoma and correlation with excision repair cross-complementation group 1
      expression and genotype.
AB  - BACKGROUND AND OBJECTIVE: Expression of excision repair cross-complementation
      group 1 (ERCC1) is recognized as a favourable prognostic marker in patients who
      have undergone surgical resection of non-small cell lung cancer (NSCLC). However,
      in patients treated with adjuvant chemotherapy after surgical resection, ERCC1
      correlated with poor prognosis. Class III beta tubulin (TUBB3) is also known to
      be a predictive marker of the efficacy of treatment with taxanes or vinorelbine.
      METHODS: Tumour tissues (n = 363) from patients with surgically resected NSCLC
      were analysed retrospectively. Tissue sections were labelled with ERCC1- and
      TUBB3-specific antibodies. Using genomic DNA from 262 patients, single nucleotide
      polymorphisms of the ERCC1 gene (T19007C and C8092A) were genotyped by PCR
      restriction fragment length polymorphism analysis. RESULTS: Only 5.9% of patients
      with stage I disease (14/238) and 61.6% of patients with stages II-III disease
      (77/125) received adjuvant chemotherapy. Relapses were noted in 30.6% (111) of
      patients, and among these, 31 ultimately succumbed. The relapse rate (RR) was
      24.8% for stage I disease, and 41.6% for stages II-III disease. The RR was
      significantly lower in ERCC1-positive (24.3%) as compared with ERCC1-negative
      patients (36.3%, P = 0.014) and was lower in patients with the AA/CA genotype at
      the ERCC1 C8092A locus (29.5%) compared with those with the CC genotype (42.1%, P
      = 0.034). The median disease-free survival (DFS) time was 62.3 months. DFS was
      significantly greater in ERCC1-positive patients (62.3 months) than in ERCC1
      negative patients (48.0 months, P = 0.042). In a multivariate analysis, ERCC1
      expression and the C8092A polymorphism were independent prognostic factors in
      patients with stage I disease who were naive to chemotherapy. CONCLUSIONS: ERCC1
      expression and the AA/CA genotype at the C8092A locus were correlated with a good
      prognosis in patients who had undergone surgical resection of NSCLC.

PMID- 21899658
TI  - Pilot study comparing SPECT perfusion scintigraphy with CT pulmonary angiography
      in chronic thromboembolic pulmonary hypertension.
AB  - BACKGROUND AND OBJECTIVE: The management of chronic thromboembolic pulmonary
      hypertension (CTEPH) is dependent on the extent of pulmonary artery obstruction,
      which is usually evaluated by planar perfusion scanning and CT pulmonary
      angiography (CTPA). We previously reported that SPECT perfusion scanning is more
      sensitive than planar scanning for detecting vascular obstruction in CTEPH. The
      purpose of this study is to compare SPECT with CTPA for detecting segmental
      pulmonary artery obstruction in CTEPH. METHODS: SPECT and CTPA were carried out
      before pulmonary endarterectomy in 12 CTEPH patients. Field experts documented
      the anatomical distribution of perfusion defects disclosed by SPECT, the
      anatomical distribution of pulmonary arterial filling defects disclosed by CTPA
      and the segmental anatomy of the vascular obstructions based on a review of
      clinical and pathology records, without knowledge of scan results. RESULTS:
      Clinical/pathological evaluation disclosed 140 obstructed (15.5 +/- 2.5 per
      patient) and 40 unobstructed lung segments. SPECT scanning identified 87/140
      (62%) of the obstructed and 29/40 (72%) of the unobstructed segments. By
      comparison, CTPA identified 67/140 (47.8%) of the obstructed and 32/40 (80%) of
      the unobstructed segments. Sensitivity for detecting obstructed segments was
      significantly higher for SPECT compared with CTPA (62 +/- 4.1% vs 47.8 +/- 2.9%,
      respectively; P = 0.03). CONCLUSIONS: SPECT is more sensitive than CTPA for
      identifying obstructed segments in this small sample of CTEPH patients. However,
      even SPECT under-represents the extent of vascular obstruction from this disease.

PMID- 21899659
TI  - Skin delivery of short hairpin RNA of indoleamine 2,3 dioxygenase induces
      antitumor immunity against orthotopic and metastatic liver cancer.
AB  - Liver cancer is one of the most malignant cancers in the world and has a high
      rate of metastasis. Therefore, development of a novel therapy for liver cancer is
      a critical issue. Indoleamine 2,3-dioxygenase (IDO) is known as a negative immune
      regulator in dendritic cells. Our previous study demonstrated that skin delivery
      of IDO short hairpin RNA (shRNA) induced antitumor immunity in subcutaneous
      bladder and colon tumor models. Because the immunological environment is quite
      different between skin and liver, it is essential to evaluate whether skin
      delivery of IDO shRNA is an effective treatment in metastatic and orthotopic
      animal tumor models. In the present study, IDO shRNA inhibited tumor growth in
      subcutaneous, metastatic and orthotopic liver tumor models. The cytotoxicity of
      splenocytes was significantly elevated in mice treated with IDO shRNA in the
      orthotopic and metastatic tumor models. Interleukin (IL)-12 and interferon (IFN)
      gamma mRNA expression were upregulated while IL-10 was downregulated in the
      inguinal lymph nodes, which were collected from IDO shRNA-treated mice. Similar
      results were observed in the spleens of mice inoculated with IDO shRNA by gene
      gun. The results indicate that skin administration of IDO shRNA is an effective
      therapy in orthotopic and metastatic liver cancer animal models. Indoleamine 2,3
      dioxygenase shRNA might be a potential new treatment for liver cancer in the
      future.

PMID- 21899660
TI  - Reduction of nitric oxide level enhances the radiosensitivity of hypoxic non
      small cell lung cancer.
AB  - The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (E-TKI)
      resistance has emerged as an important clinical issue. To overcome this
      resistance, researchers have examined different modalities, either for use as a
      monotherapy or in combination with E-TKI therapy. In the present study, we
      investigated whether a decrease in nitric oxide (NO) levels affects the
      radiosensitization of non-small cell lung cancer (NSCLC) cell lines. A549 and
      H3255 NSCLC cells were examined. They were subjected to hypoxic conditions and
      monotherapy, or combined therapy using radiation and N(G) -monomethyl-l-arginine,
      monoacetate (LNMMA). Reductions in nitric oxide levels enhanced the
      radiosensitivity of both cell lines and significantly reduced the expression of
      both hypoxia-inducible factor-1alpha (HIF-1alpha) and EGFR in H3255 cells
      compared to A549 cells. Since NO is significantly associated with cell
      metabolism, we measured the levels of pyruvate dehydrogenase kinase-1 (PDK-1),
      reactive oxygen species, and oxygen and observed that the expression of PDK-1 was
      significantly reduced. This reduction was seen simultaneously after the silencing
      of HIF-1alpha; however, not following LNMMA treatment. The oxygen concentration
      was significantly increased in the treated cells, and their viability decreased
      in parallel. Reactive oxygen species were decreased after LNMMA and radiation
      treatment. Adding EGFR-TKI to cells with reduced NO levels further suppressed
      cell viability when combined with radiation. This study suggests that a reduction
      in the NO level might substantially overcome the radioresistance of mutant NSCLC
      cells.

PMID- 21899661
TI  - Regulation of microRNA expression by hepatocyte growth factor in human head and
      neck squamous cell carcinoma.
AB  - Hepatocyte growth factor (HGF) is a multifunctional molecule that acts as
      mitogen, motogen, and/or morphogen in a variety of cells. MET, a specific
      receptor tyrosine kinase for HGF, is upregulated in various tumors including
      squamous cell carcinoma of the human head and neck (HNSCC), but how HGF affects
      the expression of downstream functional genes has not yet been elucidated in
      detail. In the present study, we examined the expression of microRNA (miRNA), non
      coding small RNA that regulate cell proliferation and functions by interfering
      with the translation of target mRNA, with or without HGF stimulation in HNSCC
      cell line HSC3. Among several miRNAs, in which the expression was altered after
      HGF stimulation, we focused on miR-200c and miR-27b, both of which were
      drastically downregulated after HGF stimulation. Expression of ZEB1, a target
      mRNA for miR-200c, was upregulated 3 and 6 h after HGF stimulation, and that of E
      cadherin, a downstream molecule of ZEB1, was downregulated 12 h after HGF
      stimulation. Expression of ST14/matriptase, an enzyme for extracellular matrix
      (ECM) degradation and HGF activation and a target mRNA for miR-27b, was
      drastically upregulated in the protein level after HGF stimulation, although it
      was not statistically altered in the mRNA level. These results suggest that miR
      200c and miR-27b downregulated by HGF might play an important role in epithelial
      mesenchymal transition mediated by ZEB1/E-cadherin and ECM degradation and HGF
      autoactivation mediated by ST14/matriptase, respectively. Altered expression of
      miRNA directly regulated by HGF might contribute enhanced progressive and
      invasive characteristics of HNSCC by regulating the translation of HGF-induced
      functional molecules.

PMID- 21899662
TI  - A single-arm, open-label study of alemtuzumab in treatment-refractory patients
      with multiple sclerosis.
AB  - BACKGROUND: Alemtuzumab (CD52-specific humanized monoclonal antibody) was found
      to be an effective therapy for treatment-naive patients with relapsing-remitting
      multiple sclerosis. OBJECTIVE: Evaluate alemtuzumab's effects in patients with
      treatment-refractory relapsing-remitting multiple sclerosis. METHODS: Forty-five
      relapsing-remitting multiple sclerosis patients who experienced >=2 relapses
      during 2 years prior to the study entry whilst receiving interferon therapy were
      administered 24 mg i.v. alemtuzumab/day for 5 days at baseline and 3 days 12
      months later. Patients received premedication with 1 g i.v. methylprednisolone on
      days 1-3 at both times. RESULTS: After 2-year follow-up, the annualized relapse
      rate was reduced by 94% compared to pre-treatment levels, from 1.6 (2 years prior
      to treatment) to 0.17 for the 2 years following (P<0.0001). Moreover, 86% of
      patients showed stable or improved scores on the Expanded Disability Status
      Scale, and only 1 experienced an increase in disability lasting >=6 months. The
      majority (70-88%) showed stable or improved leg, arm and cognitive function as
      measured by the Multiple Sclerosis Functional Composite. Serious adverse events
      observed in single patients were transient neutropenia and pneumonia, pulmonary
      emboli and deep vein thrombosis. Five patients developed clinical thyroid
      disorders but no opportunistic infections or cases of immune thrombocytopenic
      purpura were observed. CONCLUSIONS: Alemtuzumab effectively reduced relapse rates
      and improved clinical scores in patients with active relapsing-remitting multiple
      sclerosis not controlled by interferon therapy.

PMID- 21899663
TI  - Outcomes of mentored, grant-funded fellowship training in haemostasis
      /thrombosis: findings from a nested case-control survey study.
AB  - Successful strategies by which to effectively recruit and retain academic
      subspecialists in benign haematology have not been established. To evaluate the
      effectiveness of a grant-funded, mentored fellowship with respect to retention
      and early career goals in haemostasis/thrombosis, we sought to compare outcomes
      for graduates of a grant-funded, mentored fellowship training programme in
      haemostasis/thrombosis [the National Hemophilia Foundation (NHF)-Baxter Clinical
      Fellowship Award] during conventional haematology/oncology fellowship training
      (cases), vs. their training peers who were graduates of conventional
      haematology/oncology fellowship training alone (controls), via a nested case
      control survey study. Survey response rate was 85% (11/13) for cases and 90%
      (9/10) for controls. All respondents had pursued careers in academic
      haematology/oncology. Median (range) percent time spent in benign haematology
      postfellowship was 98% (70-100%) for cases vs. 0% (0-20%) for controls. Time
      spent in research was significantly greater among cases than controls (median 80%
      [range: 42-90%] vs. 55% [10-80%], respectively; P = 0.01). By years 3-4
      postfellowship, median annual number of peer-reviewed publications was higher for
      cases than controls (3.5 vs. 1.0; P = 0.01). Cases were also more successful in
      grant funding (including K-awards). These data suggest that a grant-funded,
      mentored fellowship training programme in haemostasis/thrombosis may be superior
      to conventional haematology/oncology fellowship training alone with respect to
      outcomes of retention in clinical care/research, early-career grant funding and
      publication productivity.

PMID- 21899664
TI  - The influence of prophylactic factor VIII in severe haemophilia A.
AB  - Haemophilia A individuals displaying a similar genetic defect have heterogeneous
      clinical phenotypes. Our objective was to evaluate the underlying effect of
      exogenous factor (f)VIII on tissue factor (Tf)-initiated blood coagulation in
      severe haemophilia utilizing both empirical and computational models. We
      investigated twenty-five clinically severe haemophilia A patients. All
      individuals were on fVIII prophylaxis and had not received fVIII from 0.25 to 4
      days prior to phlebotomy. Coagulation was initiated by the addition of Tf to
      contact-pathway inhibited whole blood +/- an anti-fVIII antibody. Aliquots were
      quenched over 20 min and analyzed for thrombin generation and fibrin formation.
      Coagulation factor levels were obtained and used to computationally predict
      thrombin generation with fVIII set to either zero or its value at the time of the
      draw. As a result of prophylactic fVIII, at the time of the blood draw, the
      individuals had fVIII levels that ranged from <1% to 22%. Thrombin generation
      (maximum level and rate) in both empirical and computational systems increased as
      the level of fVIII increased. FXIII activation rates also increased as the fVIII
      level increased. Upon suppression of fVIII, thrombin generation became comparable
      in both systems. Plasma composition analysis showed a negative correlation
      between bleeding history and computational thrombin generation in the absence of
      fVIII. Residual prophylactic fVIII directly causes an increase in thrombin
      generation and fibrin cross-linking in individuals with clinically severe
      haemophilia A. The combination of each individual's coagulation factors (outside
      of fVIII) determine each individual's baseline thrombin potential and may affect
      bleeding risk.

PMID- 21899665
TI  - A case of three-year-old boy with severe haemophilia A on prophylaxis identified
      with a chronic subdural haematoma 2 years after the first episode of acute
      subdural bleeding.

PMID- 21899666
TI  - Autoantibodies in Sjogren's syndrome patients acutely inhibit muscarinic receptor
      function.
AB  - OBJECTIVES: Autoantibodies from the sera of Sjogren's syndrome patients (SS IgG)
      have been suggested to inhibit muscarinic receptor function. However, the acute
      nature of such an inhibitory effect remains controversial. In this study, we
      investigated the acute effects of SS IgG on muscarinic receptor function in human
      submandibular gland (HSG) cells. METHODS: The effects of autoantibodies on
      muscarinic receptor function were studied using microspectrofluorimetry, whole
      cell patch clamp, immunofluorescence confocal microscopy, and a co
      immunoprecipitation assay. RESULTS: Carbachol (CCh) was found to consistently
      increase intracellular calcium concentration ([Ca(2+) ](i) ) and activate K(+)
      current in HSG cells. However, pretreatment of the cells with SS IgG for 5 or 30
      min significantly attenuated these responses, with a substantially more prominent
      effect after 30 min of treatment. Like CCh, adenosine 5'-triphosphate (ATP) also
      increased [Ca(2+) ](i) and activated K(+) currents in HSG cells, although
      pretreatment with SS IgG did not affect the cellular response to ATP. CCh was
      found to reorganize alpha-fodrin in HSG cells in a Ca(2+) -dependent manner.
      However, pretreatment with SS IgG prevented the cytoskeletal reorganization of
      alpha-fodrin induced by CCh. CONCLUSIONS: SS IgG acutely and reversibly inhibited
      muscarinic receptor function, thereby inhibiting the Ca(2+) mobilization
      necessary for the activation of K(+) currents and alpha-fodrin reorganization in
      HSG cells.

PMID- 21899667
TI  - Distinct immunomodulatory properties of Lactobacillus paracasei strains.
AB  - AIMS: This study was performed to ascertain the immunomodulatory effect of
      Lactobacillus paracasei strains. These strains were also genetically
      characterized. METHODS AND RESULTS: The strains were genetically differentiated
      by using the fluorescent-amplified fragment length polymorphism technique, which
      led to the identification of several molecular markers unique to each strain. To
      determine the immunomodulatory properties, we evaluated the effect of strains on
      dendritic cell maturation, dextran uptake, ability to induce proliferation of
      allogenic T cells and cytokine secretion. The results indicated that all the
      strains stimulated phenotypic maturation of dendritic cells (DCs), but they acted
      differently on DCs in relation to the other tested properties; notably, a
      different effect on cytokine secretion was detected. CONCLUSIONS: The results of
      this study revealed different immunomodulatory properties of strains of the
      species Lact. paracasei. Strain IMPC 4.1 showed an interesting anti-inflammatory
      ability. Probiotic strains IMPC 2.1 and LMG P-17806 were characterized by a
      similar and intermediate ability to induce cytokine secretion in contrast to the
      very low ability of strain LMG 23554. SIGNIFICANCE AND IMPACT OF STUDY: Our
      results confirm that each single strain of a bacterial species appears to
      influence the immune system in a peculiar manner. The evaluation of the different
      types and/or levels of cytokines whose secretion is induced by each strain could
      be relevant to define its pro- or anti-inflammatory properties and its more
      appropriate clinical use.

PMID- 21899668
TI  - Investigating interactional competencies in Parkinson's disease: the potential
      benefits of a conversation analytic approach.
AB  - BACKGROUND: Around 70% of people who develop Parkinson's disease (PD) experience
      speech and voice changes. Clinicians often find that when asked about their
      primary communication concerns, PD clients will talk about the difficulties they
      have 'getting into' conversations. This is an important area for clients and it
      has implications for quality of life and clinical management. AIMS: To review the
      extant literature on PD and communication impairments in order to reveal key
      topic areas, the range of methodologies applied, and any gaps in knowledge
      relating to PD and social interaction and how these might be usefully addressed.
      METHODS & PROCEDURES: A systematic search of a number of key databases and
      available grey literatures regarding PD and communication impairment was
      conducted (including motor speech changes, intelligibility, cognitive/language
      changes) to obtain a sense of key areas and methodologies applied. Research
      applying conversation analysis in the field of communication disability was also
      reviewed to illustrate the value of this methodology in uncovering common
      interactional difficulties, and in revealing the use of strategic collaborative
      competencies in naturally occurring conversation. In addition, available speech
      and language therapy assessment and intervention approaches to PD were examined
      with a view to their effectiveness in promoting individualized intervention
      planning and advice-giving for everyday interaction. MAIN CONTRIBUTION: A great
      deal has been written about the deficits underpinning communication changes in PD
      and the impact of communication disability on the self and others as measured in
      a clinical setting. Less is known about what happens for this client group in
      everyday conversations outside of the clinic. Current speech and language therapy
      assessments and interventions focus on the individual and are largely impairment
      based or focused on compensatory speaker-oriented techniques. A conversation
      analysis approach would complement basic research on what actually happens in
      everyday conversation for people with PD and their co-participants. CONCLUSIONS &
      IMPLICATIONS: The potential benefits of a conversation analysis approach to
      communication disability in PD include enabling a shift in clinical focus from
      individual impairment onto strategic collaborative competencies. This would have
      implications for client-centred intervention planning and the development of new
      and complementary clinical resources addressing participation. The impact would
      be new and improved support for those living with the condition as well as their
      families and carers.

PMID- 21899669
TI  - Acquired dysarthria in conversation: methods of resolving understandability
      problems.
AB  - BACKGROUND: People with acquired progressive dysarthria typically experience
      increased problems with intelligibility in everyday conversation as their disease
      progresses. Such problems are likely to impact on both the person with dysarthria
      and those with whom they interact. If this is the case then we may ask questions
      not just about the nature of these problems but how it is that such problems are
      dealt with by participants when they occur. AIMS: To investigate ways through
      which problems resulting from dysarthria in everyday conversation are resolved by
      participants. Further, to examine some of the features of repair resolution,
      particularly where understanding of self-repair attempts themselves prove
      difficult. METHODS & PROCEDURES: Video data of natural conversation from two
      dyads were selected for this paper. One dyad features a 58 year-old man with
      multiple sclerosis and moderate intelligibility problems, the other a 79 year-old
      woman with motor neurone disease with mild to moderate intelligibility problems.
      Both elected to be recorded in conversation with their spouses. The dyads were
      video-recorded at home with no researcher present. Using the methods of
      Conversation Analysis (CA) a collection of sequences was identified and
      transcribed. The sequences were analysed with reference to how the participants
      resolve problems in the understanding of dysarthric speech. OUTCOMES & RESULTS:
      It is shown how some problems resulting from dysarthria in conversation can be
      resolved relatively quickly, particularly where a specific element of a prior
      turn is highlighted by the recipient as problematic. In other instances, the
      recipient's understanding problem may be more global. These result in longer
      repair sequences in which problematic elements are addressed individually. Such a
      resolution method is ultimately successful but may also be characterised by
      additional understanding problems. These findings draw attention to an important
      distinction between intelligibility and understandability. CONCLUSIONS &
      IMPLICATIONS: It is concluded that problems resulting from dysarthria in
      conversation can require extensive repair work involving both parties. This has
      implications for the assessment of dysarthria in everyday conversation and also
      the promotion of intervention strategies that encompass the activities of both
      participants when dealing with dysarthria in interaction. These findings may be
      usefully employed in informing both direct clinical work and through training
      those who work with this client group and their significant others.

PMID- 21899670
TI  - Why do people lose their friends after a stroke?
AB  - BACKGROUND: It is well-known that people lose friends after a stroke; what is
      less well understood is why this occurs. AIMS: This study explored why people
      lose contact with their friends, and whether there are any protective factors. It
      also examined how friendship loss and change is perceived by the individual.
      METHODS AND PROCEDURES: Participants with a first stroke were recruited from one
      acute stroke unit in the UK. In-depth qualitative interviews took place between 8
      and 15 months post stroke. OUTCOMES AND RESULTS: 29 participants were recruited
      of whom 10 had aphasia. The main reasons given for losing friends were: loss of
      shared activities, reduced energy levels, physical disability, aphasia, unhelpful
      responses of others, environmental barriers, and changing social desires. The
      subset of participants who experienced the most extensive loss of friends were
      those who described a sense that they were 'closing in' on themselves leading to
      a withdrawal from social contact and a new preference for meeting only close
      friends and family. Those with aphasia experienced the most hurtful negative
      responses from others and found it more difficult to retain their friends unless
      they had strong supportive friendship patterns prior to the stroke. The factors
      which helped to protect friendships included: having a shared history, friends
      who showed concern, who lived locally, where the friendship was not activity
      based, and where the participant had a 'friends-based' social network prior to
      the stroke. CONCLUSIONS AND IMPLICATIONS: Given the link between depression and
      loss of friends post stroke, supporting an individual in maintaining a social
      network is likely to be beneficial. For intervention to be effective, however, it
      may need to take into account not only the impact of new physical and language
      disabilities, but also changing social desires.

PMID- 21899671
TI  - Objective eye-gaze behaviour during face-to-face communication with proficient
      alaryngeal speakers: a preliminary study.
AB  - BACKGROUND: There is a large body of research demonstrating the impact of visual
      information on speaker intelligibility in both normal and disordered speaker
      populations. However, there is minimal information on which specific visual
      features listeners find salient during conversational discourse. AIMS: To
      investigate listeners' eye-gaze behaviour during face-to-face conversation with
      normal, laryngeal and proficient alaryngeal speakers. METHODS & PROCEDURES: Sixty
      participants individually participated in a 10-min conversation with one of four
      speakers (typical laryngeal, tracheoesophageal, oesophageal, electrolaryngeal; 15
      participants randomly assigned to one mode of speech). All speakers were > 85%
      intelligible and were judged to be 'proficient' by two certified speech-language
      pathologists. Participants were fitted with a head-mounted eye-gaze tracking
      device (Mobile Eye, ASL) that calculated the region of interest and mean duration
      of eye-gaze. Self-reported gaze behaviour was also obtained following the
      conversation using a 10 cm visual analogue scale. OUTCOMES & RESULTS: While
      listening, participants viewed the lower facial region of the oesophageal speaker
      more than the normal or tracheoesophageal speaker. Results of non-hierarchical
      cluster analyses showed that while listening, the pattern of eye-gaze was
      predominantly directed at the lower face of the oesophageal and electrolaryngeal
      speaker and more evenly dispersed among the background, lower face, and eyes of
      the normal and tracheoesophageal speakers. Finally, results show a low
      correlation between self-reported eye-gaze behaviour and objective regions of
      interest data. CONCLUSIONS & IMPLICATIONS: Overall, results suggest similar eye
      gaze behaviour when healthy controls converse with normal and tracheoesophageal
      speakers and that participants had significantly different eye-gaze patterns when
      conversing with an oesophageal speaker. Results are discussed in terms of
      existing eye-gaze data and its potential implications on auditory-visual speech
      perception.

PMID- 21899672
TI  - Botox((r)) to reduce drooling in a paediatric population with neurological
      impairments: a Phase I study.
AB  - BACKGROUND: The treatment of drooling in a paediatric population with
      neurological impairments is clinically challenging. Surgery is considered
      invasive, while behaviour modification techniques, correction of situational
      factors and oral-motor therapy do not always produce sustained improvement. In
      recent years the use of Botox(r) to decrease drooling has been investigated.
      AIMS: To review the clinical data from a Drooling Treatment Project for children
      with neurological impairments and to establish the validity of the drooling
      severity and frequency rating scales, establishing Phase I-level information
      about the therapeutic use of submandibular salivary gland injections of Botox(r)
      in various contexts. METHOD & PROCEDURES: A retrospective, explanatory design was
      used to review the data. Nine children, seven with cerebral palsy and two with
      operculum syndrome, ranging in age from 5 to 17 years (mean = 9;3 years) were
      included. Drooling was assessed by qualified speech-language therapists using
      drooling rating scales, in five different situations and at different time points
      pre- and post-Botox(r) injection up to 6 months. Quantitative and qualitative
      analyses were computed. Parents'/primary caregivers' perceptions of drooling and
      treatment with Botox(r) were also considered using an interview form and a
      quality of life questionnaire. OUTCOMES & RESULTS: Statistically significant
      reductions in drooling with large effect sizes were obtained in the communicating
      and general appearance situations. There was a difference in the pattern of
      response between the children with cerebral palsy and those with operculum
      syndrome. Discrepancies between the parents and the speech-language therapists
      regarding the context of drooling reduction were found. Most parents/primary
      caregivers felt their children's lives and their own had improved following the
      Botox(r) injection and would repeat the treatment. The drooling rating scales
      were a valid method to assess drooling in a clinical situation. CONCLUSIONS &
      IMPLICATIONS: In the clinical setting of the Drooling Treatment Project, the
      results indicated that the context in which drooling occurs is an important
      factor and suggested the value of considering the situational context when making
      drooling judgments. Further, there was a difference in the pattern of response
      between the children with cerebral palsy and those with operculum syndrome,
      suggesting that aetiology may be involved in the response to Botox(r).

PMID- 21899673
TI  - A cross-linguistic study of real-word and non-word repetition as predictors of
      grammatical competence in children with typical language development.
AB  - BACKGROUND: Although relationships among non-word repetition, real-word
      repetition and grammatical ability have been documented, it is important to study
      whether the specific nature of these relationships is tied to the characteristics
      of a given language. AIMS: The aim of this study is to explore the potential
      cross-linguistic differences (Italian and English) in the relationship among non
      word repetition, real-word repetition, and grammatical ability in three-and four
      year-old children with typical language development. METHODS & PROCEDURES: To
      reach this goal, two repetition tasks (one real-word list and one non-word list
      for each language) were used. In Italian the grammatical categories were the
      third person plural inflection and the direct-object clitic pronouns, while in
      English they were the third person singular present tense inflection and the past
      tense in regular and irregular forms. OUTCOMES & RESULTS: A cross-linguistic
      comparison showed that in both Italian and English, non-word repetition was a
      significant predictor of grammatical ability. However, performance on real-word
      repetition explained children's grammatical ability in Italian but not in
      English. CONCLUSIONS & IMPLICATIONS: Abilities underlying non-word repetition
      performance (e.g., the processing and/or storage of phonological material) play
      an important role in the development of children's grammatical abilities in both
      languages. Lexical ability (indexed by real-word repetition) showed a close
      relationship to grammatical ability in Italian but not in English. Implications
      of the findings are discussed in terms of cross-linguistic differences, genetic
      research, clinical intervention and methodological issues.

PMID- 21899674
TI  - Responsiveness of children with specific language impairment and maternal repairs
      during shared book reading.
AB  - BACKGROUND: Previous studies indicate that (1) children with specific language
      impairment (SLI) produce a high number of problematic answers during shared book
      reading, and that (2) adult communicative input has a key role in supporting
      child responsiveness. However, little is known about the strategies used by
      parents to repair children's inadequate answers and their effectiveness in
      supporting appropriate responses. AIMS: Repairs (any utterance aimed to correct a
      child's problematic answer) produced by mothers of children with SLI and mothers
      of typically developing children during shared reading conversation were
      compared: (1) to examine whether there are significant differences in their
      features, and to what extent these differences (if any) are accounted for by
      limitations in child responsiveness and language abilities; and (2) to assess
      whether-and in which cases-maternal repairs are effective in eliciting
      appropriate answers from children with SLI. METHODS & PROCEDURES: Ten preschool
      aged children with SLI, ten age-matched typically developing children, and ten
      mean length of utterance-matched typically developing children with their mothers
      participated in the study. Each mother-child dyad was videotaped during four
      sessions of shared book reading at home. Each maternal repair was coded according
      to the level of support (i.e., presence of crucial information and familiar
      topic) provided to elicit the child's correct answer. Each child's answer
      following a maternal repair was coded on the basis of both linguistic production
      and content appropriateness. OUTCOMES & RESULTS: Mothers of children with SLI
      produced significantly more high-supportive repairs than mothers of age-matched
      children, but not more than mothers of mean length of utterance-matched younger
      children. Sequential analysis applied to maternal repairs and children's answers
      showed that supportive repairs significantly affected the occurrence of minimally
      acceptable answers produced by children with SLI, while non-supportive repairs
      affected significantly the occurrence of inadequate answers. Children with SLI
      behaved in a similar way to mean length of utterance-matched younger children,
      showing spontaneous motivation to imitate crucial information included in high
      supportive repairs. CONCLUSIONS & IMPLICATIONS: The findings suggest that mothers
      of children with SLI adjust their repairs to their children's linguistic
      limitations. The use of supportive repairs is functional to model the children's
      answers, enables them to practise new words, and contributes to the children's
      experience of being an active interlocutor. These findings have a potential
      clinical value that can be used in language intervention programmes based on
      shared book reading.

PMID- 21899675
TI  - Maximizing health literacy and client recall in a developing context: speech
      language therapist and client perspectives.
AB  - BACKGROUND: In the field of speech-language therapy, limited research has been
      conducted with regards to health literacy and client recall. However, speech
      language therapists frequently provide a considerable amount of information for
      clients to understand, apply and review in order to manage their (or their
      child's) health. AIMS: This study aimed to investigate (1) issues around clients'
      health literacy and recall of information; and (2) how these issues can be
      overcome in speech-language therapy in a developing context. METHOD & PROCEDURES:
      An exploratory study was undertaken with specific focus on speech-language
      therapists and their clients who had previously received treatment for dysphagia,
      voice disorders (including laryngectomies), and cleft lip and/or palate
      management. They were recruited at public tertiary hospitals and primary
      healthcare clinics in Cape Town, South Africa. Data were gathered through focus
      group discussions and qualitatively analysed using a content-driven
      immersion/crystallization style. OUTCOMES & RESULTS: Five themes and 13 subthemes
      were identified. Speech-language therapists currently use mostly low-technology
      strategies to manage issues of health literacy and client recall, and frequently
      view poor outcomes as being related to clients themselves and a lack of
      compliance. CONCLUSIONS & IMPLICATIONS: An understanding of context,
      intercultural health literacy and client-provider concordance are important
      factors that should inform the clinical practice of speech-language therapy.
      There is a need to develop effective strategies for information provision and
      review post-consultation. Speech-language therapists have an important mediating
      role in cross-cultural communication.

PMID- 21899676
TI  - Using a microscope to change a speech valve.
AB  - Replacing a speech valve can be a difficult procedure to learn and perform. In
      this letter the authors propose a method using an operating microscope, which
      their department has found useful in performing this procedure, and in teaching
      trainees.

PMID- 21899677
TI  - Cdc42 regulates multiple membrane traffic events in fission yeast.
AB  - Fission yeast Cdc42 regulates polarized growth and is involved in For3 formin
      activation and actin cable assembly. We show here that a thermosensitive strain
      carrying the cdc42L160S allele has membrane traffic defects independent of the
      actin cable defects. This strain has decreased acid phosphatase (AP) secretion,
      intracellular accumulation of vesicles and fragmentation of vacuoles. In
      addition, the exocyst is not localized to the tips of these cells. Overproduction
      of the scaffold protein Pob1 suppressed cdc42L160S thermosensitive growth and
      restored exocyst localization and AP secretion. The GTPase Rho3 also suppressed
      cdc42L160S thermosensitivity, restored exocyst localization and AP secretion.
      However, Rho3 did not restore the actin cables in these cells as Pob1 does.
      Similarly, overexpression of psy1(+) , coding a syntaxin (t-SNARE) homolog, or of
      ypt2(+) , coding an SEC4 homolog in fission yeast, rescued growth at high
      temperature but did not restore actin cables, nor the exocyst-polarized
      localization. cdc42L160S cells also have defects in vacuole formation that were
      rescued by Pob1, Rho3 and Psy1. All together, we propose that Cdc42 and the
      scaffold Pob1 are required for membrane trafficking and fusion, contributing to
      polarized secretion, endosome recycling, vacuole formation and growth.

PMID- 21899678
TI  - Identification of sorting motifs of AtbetaFruct4 for trafficking from the ER to
      the vacuole through the Golgi and PVC.
AB  - Although much is known about the molecular mechanisms involved in transporting
      soluble proteins to the central vacuole, the mechanisms governing the trafficking
      of membrane proteins remain largely unknown. In this study, we investigated the
      mechanism involved in targeting the membrane protein, AtbetaFructosidase 4
      (AtbetaFruct4), to the central vacuole in protoplasts. AtbetaFruct4 as a green
      fluorescent protein (GFP) fusion protein was transported as a membrane protein
      during transit from the endoplasmic reticulum (ER) through the Golgi apparatus
      and the prevacuolar compartment (PVC). The N-terminal cytosolic domain of
      AtbetaFruct4 was sufficient for transport from the ER to the central vacuole and
      contained sequence motifs required for trafficking. The sequence motifs, LL and
      PI, were found to be critical for ER exit, while the EEE and LCPYTRL sequence
      motifs played roles in trafficking primarily from the trans Golgi network (TGN)
      to the PVC and from the PVC to the central vacuole, respectively. In addition,
      actin filaments and AtRabF2a, a Rab GTPase, played critical roles in vacuolar
      trafficking at the TGN and PVC, respectively. On the basis of these results, we
      propose that the vacuolar trafficking of AtbetaFruct4 depends on multiple
      sequence motifs located at the N-terminal cytoplasmic domain that function as
      exit and/or sorting signals in different stages during the trafficking process.

PMID- 21899679
TI  - Using computed tomography coronary angiography to evaluate patients with acute
      chest pain: putting the horse before the cart.

PMID- 21899680
TI  - Practical guidelines for the acute emergency sedation of the severely agitated
      older patient.
AB  - The vulnerability of older people to serious underlying medical illness and
      adverse effects of psychotropics means that the safe and effective treatment of
      severe agitation can be lifesaving, the primary management goals being to create
      a safe environment for the patient and others, and to facilitate assessment and
      treatment. We review the literature on acute sedation and provide practical
      guidelines for the management of this problem addressing a range of issues,
      including aetiology, assessment, pharmacological and non-pharmacological
      strategies, restraint and consent. The assessment of the agitated older patient
      must include concurrent assessment of the likely aetiology of, the risks posed
      by, and the risks/benefits of management options for, the agitation. A range of
      environmental modifications and non-pharmacological strategies might be
      implemented to maximize the safety of the patient and others. Physical restraints
      should only be considered after appropriate assessment and trial of alternative
      management and if the risk of restraint is less than the risk of the behaviour.
      Limited evidence supports a range of pharmacological options from traditional
      antipsychotics to atypical antipsychotics and benzodiazepines. It is advised to
      start low and go slow, using small increments of dose increase. Medical staff are
      frequently called to sedate agitated older patients in hospital settings, often
      after hours, with limited access to relevant medical information and history.
      Safe and effective management necessitates adequate assessment of the aetiology
      of the agitation, exhausting all non-pharmacological strategies, and resorting to
      pharmacological and/or physical restraint only when necessary, judiciously and
      for a short-term period, with frequent review and the obtaining of consent as
      soon as possible.

PMID- 21899681
TI  - Combined catheter thrombus fragmentation and fibrinolysis for acute pulmonary
      embolism.
AB  - AIMS: The aim of this study is to evaluate the effectiveness and safety of
      combined catheter thrombus fragmentation and fibrinolysis for acute pulmonary
      embolism (PE). METHODS: Forty-six patients (19 men and 27 women, average age 52.3
      +/- 13.4 years) with acute PE and right ventricular dysfunction were treated by
      mechanical thrombus fragmentation with a percutaneous transluminal coronary
      angioplasty guide catheter. Urokinase was injected into the culprit pulmonary
      artery after catheter thrombus fragmentation in all patients. RESULT: Clinical
      success was achieved in all patients. After the treatment, the average pulmonary
      artery pressure was decreased from 57.2 +/- 6.2 to 36.3 +/- 4.1 mmHg (P < 0.01).
      The oxygen saturation rate was raised from 81.4 +/- 4.3% to 97.0 +/- 2.0% (P <
      0.01), and the right ventricular function was improved. There was no in-hospital
      mortality and there were no major complications, such as haemorrhage. Patients
      were treated with warfarin for 6 months with no signs of PE recurrence during the
      follow up. CONCLUSION: In PE patients with right ventricular dysfunction and
      unstable haemodynamics, combined catheter thrombus fragmentation and thrombolysis
      appears to be a useful therapeutic strategy. In PE patients with right
      ventricular dysfunction and stable haemodynamics, randomized trials are still
      required to show that combination of catheter-directed thrombus fragmentation and
      thrombolysis is superior to standard anticoagulation.

PMID- 21899682
TI  - Hypertension is an independent predictor of mean platelet volume in patients with
      acute ischaemic stroke.
AB  - INTRODUCTION: Mean platelet volume (MPV) was shown to be significantly increased
      in patients with acute ischaemic stroke, especially in non-lacunar strokes.
      Moreover, some studies concluded that increased MPV is related to poor functional
      outcome after ischaemic stroke, although this association is still controversial.
      However, the determinants of MPV in patients with acute ischaemic stroke have
      never been investigated. SUBJECTS AND METHODS: We recorded the main demographic,
      clinical and laboratory data of consecutive patients with acute (admitted within
      24 h after stroke onset) ischaemic stroke admitted in our Neurology Service
      between January 2003 and December 2008. MPV was generated at admission by the
      Sysmex XE-2100 automated cell counter (Sysmex Corporation, Kobe, Japan) from
      ethylenediaminetetraacetic acid blood samples stored at room temperature until
      measurement. The association of these parameters with MPV was investigated in
      univariate and multivariate analysis. RESULTS: A total of 636 patients was
      included in our study. The median MPV was 10.4 +/- 0.82 fL. In univariate
      analysis, glucose (beta= 0.03, P= 0.05), serum creatinine (beta= 0.002, P= 0.02),
      haemoglobin (beta= 0.009, P < 0.001), platelet count (beta=-0.002, P < 0.001) and
      history of arterial hypertension (beta= 0.21, P= 0.005) were found to be
      significantly associated with MPV. In multivariate robust regression analysis,
      only hypertension and platelet count remained as independent determinants of MPV.
      CONCLUSIONS: In patients with acute ischaemic stroke, platelet count and history
      of hypertension are the only determinants of MPV.

PMID- 21899683
TI  - Metastatic parathyroid carcinoma initially misdiagnosed as parathyroid adenoma:
      the role of parafibromin in increasing diagnostic accuracy.
AB  - Parathyroid carcinoma, although a rare cause of primary hyperparathyroidism,
      carries a significant morbidity and mortality from severe symptomatic
      hypercalcaemia and related complications. We report a case where the diagnosis
      was not considered from the outset and review the current clinical and
      histopathological markers available to assist in the diagnosis of parathyroid
      carcinoma.

PMID- 21899684
TI  - Immune reconstitution inflammatory syndrome manifesting as development of
      multiple autoimmune disorders and skin cancer progression.
AB  - We report the case of a 56-year-old man with the rare autoimmune pathologies of
      alternating hypothyroidism and hyperthyroidism due to thyroid-stimulating hormone
      receptor antibodies, and rheumatoid arthritis as manifestations of a human
      immunodeficiency virus-related immune reconstitution inflammatory syndrome. The
      patient also developed overt progression of a pre-existing skin malignancy that
      may also be related. This case highlights immune reconstitution syndrome as an
      important differential diagnosis following antiretroviral therapy commencement,
      and that a high index of suspicion should be maintained for this rare but
      important cluster of conditions. Furthermore, the patient's genetic
      predisposition to autoimmunity provides helpful insights into the pathogenesis of
      these disorders.

PMID- 21899685
TI  - Massive hiatus hernia presenting as acute chest pain.

PMID- 21899686
TI  - Gallstone ileus.

PMID- 21899687
TI  - Has the disease identity of restless legs syndrome developed or been distorted?
      Astronauts in zero gravity may know the answer.

PMID- 21899688
TI  - Laugh headaches: a rare form of headache associated with type 1 Arnold-Chiari
      malformation.

PMID- 21899689
TI  - Dangers of ripping in body building.

PMID- 21899690
TI  - Erythrocytapheresis treatment in severe malaria.

PMID- 21899692
TI  - Scurvy: old and new.

PMID- 21899693
TI  - Tri-trophic interactions affect density dependence of seed fate in a tropical
      forest palm.
AB  - Natural enemies, especially host-specific enemies, are hypothesised to facilitate
      the coexistence of plant species by disproportionately inflicting more damage at
      increasing host abundance. However, few studies have assessed such Janzen-Connell
      mechanisms on a scale relevant for coexistence and no study has evaluated
      potential top-down influences on the specialized pests. We quantified seed
      predation by specialist invertebrates and generalist vertebrates, as well as
      larval predation on these invertebrates, for the Neotropical palm Attalea
      butyracea across ten 4-ha plots spanning 20-fold variation in palm density. As
      palm density increased, seed attack by bruchid beetles increased, whereas seed
      predation by rodents held constant. But because rodent predation on bruchid
      larvae increased disproportionately with increasing palm density, bruchid
      emergence rates and total seed predation by rodents and bruchids combined were
      both density-independent. Our results demonstrate that top-down effects can limit
      the potential of host-specific insects to induce negative-density dependence in
      plant populations.

PMID- 21899694
TI  - CHD6 chromatin remodeler is a negative modulator of influenza virus replication
      that relocates to inactive chromatin upon infection.
AB  - The influenza virus establishes close functional and structural connections with
      the nucleus of the infected cell. Thus, viral ribonucleoproteins (RNPs) are
      closely bound to chromatin components and the main constituent of viral RNPs, the
      nucleoprotein (NP) protein, interacts with histone tails. Using a yeast two
      hybrid screening, we previously found that the PA influenza virus polymerase
      subunit interacts with the CHD6 protein, a member of the CHD family of chromatin
      remodelers. Here we show that CHD6 also interacts with the viral polymerase
      complex and colocalizes with viral RNPs in the infected cells. To study the
      relationships between RNPs, chromatin and CHD6, we have analysed whether NP and
      CHD6 binds to peptides representing trimethylated lysines of histone 3 tails that
      mark transcriptionally active or inactive chromatin. Upon infection, NP binds to
      marks of repressed chromatin and, interestingly an important recruitment of CHD6
      to these heterochromatin marks occurs in this situation. Silencing experiments
      indicate that CHD6 acts as a negative modulator of influenza virus replication.
      Hence, the CHD6 association with inactive chromatin could be part of a process
      where the influenza virus triggers modifications of chromatin-associated proteins
      that could contribute to the pathogenic events used by the virus to induce host
      cell shut-off.

PMID- 21899695
TI  - Phosphatidylinositol-3-kinase (PI3K) is activated by influenza virus vRNA via the
      pathogen pattern receptor Rig-I to promote efficient type I interferon
      production.
AB  - The phosphatidylinositol-3-kinase (PI3K) was identified to be activated upon
      influenza A virus (IAV) infection. An early and transient induction of PI3K
      signalling is caused by viral attachment to cells and promotes virus entry. In
      later phases of infection the kinase is activated by the viral NS1 protein to
      prevent premature apoptosis. Besides these virus supporting functions, it was
      suggested that PI3K signalling is involved in dsRNA and IAV induced antiviral
      responses by enhancing the activity of interferon regulatory factor-3 (IRF-3).
      However, molecular mechanisms of activation remained obscure. Here we show that
      accumulation of vRNA in cells infected with influenza A or B viruses results in
      PI3K activation. Furthermore, expression of the RNA receptors Rig-I and MDA5 was
      increased upon stimulation with virion extracted vRNA or IAV infection. Using
      siRNA approaches, Rig-I was identified as pathogen receptor necessary for
      influenza virus vRNA sensing and subsequent PI3K activation in a TRIM25 and MAVS
      signalling dependent manner. Rig-I induced PI3K signalling was further shown to
      be essential for complete IRF-3 activation and consequently induction of the type
      I interferon response. These data identify PI3K as factor that is activated as
      part of the Rig-I mediated anti-pathogen response to enhance expression of type I
      interferons.

PMID- 21899696
TI  - The organization of the wall filaments and characterization of the matrix
      structures of Toxoplasma gondii cyst form.
AB  - The encystation process is a key step in Toxoplasma gondii life cycle, allowing
      the parasite to escape from the host immune system and the transmission among the
      hosts. A detailed characterization of the formation and structure of the cyst
      stage is essential for a better knowledge of toxoplasmosis. Here we isolated
      cysts from mice brains and analysed the cyst wall structure and cyst matrix
      organization using different electron microscopy techniques. Images obtained
      showed that the cyst wall presented a filamentous aspect, with circular openings
      on its surface. The filaments were organized in two layers: a compact one, facing
      the exterior of the whole cyst and a more loosen one, facing the matrix. Within
      the cyst wall, we observed tubules and a large number of vesicles. The cyst
      matrix presented vesicles of different sizes and tubules, which were organized in
      a network connecting the bradyzoites to each other and to the cyst wall. Large
      vesicles, with a granular material in their lumen of glycidic nature were
      observed. Similar vesicles were also found associated with the posterior pole of
      the bradyzoites and in proximity to the cyst wall.

PMID- 21899697
TI  - Gastric epithelial cell death caused by Helicobacter suis and Helicobacter pylori
      gamma-glutamyl transpeptidase is mainly glutathione degradation-dependent.
AB  - Helicobacter (H.) suis is the most prevalent non-H. pylori Helicobacter species
      colonizing the stomach of humans suffering from gastric disease. In the present
      study, we aimed to unravel the mechanism used by H. suis to induce gastric
      epithelial cell damage. H. suis lysate induced mainly apoptotic death of human
      gastric epithelial cells. Inhibition of gamma-glutamyl transpeptidase (GGT)
      activity present in H. suis lysate and incubation of AGS cells with purified
      native and recombinant H. suis GGT showed that this enzyme was partly responsible
      for the observed apoptosis. Supplementation of H. suis or H. pylori GGT-treated
      cells with glutathione strongly enhanced the harmful effect of both enzymes and
      resulted in the induction of oncosis/necrosis, demonstrating that H. suis and H.
      pylori GGT-mediated degradation of glutathione and the resulting formation of
      glutathione degradation products play a direct and active role in the induction
      of gastric epithelial cell death. This was preceded by an increase of
      extracellular H(2)O(2) concentrations, generated in a cell-independent manner and
      causing lipid peroxidation. In conclusion, H. suis and H. pylori GGT-mediated
      generation of pro-oxidant glutathione degradation products brings on cell damage
      and causes apoptosis or necrosis, dependent on the amount of extracellular
      glutathione available as a GGT substrate.

PMID- 21899698
TI  - Experimentally controlled downregulation of the histone chaperone FACT in
      Plasmodium berghei reveals that it is critical to male gamete fertility.
AB  - Human FACT (facilitates chromatin transcription) consists of the proteins SPT16
      and SSRP1 and acts as a histone chaperone in the (dis)assembly of nucleosome (and
      thereby chromatin) structure during transcription and DNA replication. We
      identified a Plasmodium berghei protein, termed FACT-L, with homology to the
      SPT16 subunit of FACT. Epitope tagging of FACT-L showed nuclear localization with
      high expression in the nuclei of (activated) male gametocytes. The gene encoding
      FACT-L could not be deleted indicating an essential role during blood-stage
      development. Using a 'promoter-swap' approach whereby the fact-l promoter was
      replaced by an 'asexual blood stage-specific' promoter that is silent in
      gametocytes, transcription of fact-l in promoter-swap mutant gametocytes was
      downregulated compared with wild-type gametocytes. These mutant male gametocytes
      showed delayed DNA replication and gamete formation. Male gamete fertility was
      strongly reduced while female gamete fertility was unaffected; residual ookinetes
      generated oocysts that arrested early in development and failed to enter
      sporogony. Therefore FACT is critically involved in the formation of fertile male
      gametes and parasite transmission. 'Promoter swapping' is a powerful approach for
      the functional analysis of proteins in gametocytes (and beyond) that are
      essential during asexual blood-stage development.

PMID- 21899700
TI  - Echovirus 1 infection depends on biogenesis of novel multivesicular bodies.
AB  - Non-enveloped picornavirus echovirus 1 (EV1) clusters its receptor alpha2beta1
      integrin and causes their internalization and accumulation in alpha2beta1
      integrin enriched multivesicular bodies (alpha2-MVBs). Our results here show that
      these alpha2-MVBs are distinct from acidic late endosomes/lysosomes by several
      criteria: (i) live intra-endosomal pH measurements show that alpha2-MVBs are not
      acidic, (ii) they are not positive for the late endosomal marker LBPA or Dil-LDL
      internalized to lysosomes, and (iii) simultaneous stimulation of epidermal growth
      factor receptor (EGFR) and alpha2beta1 integrin clustering leads to their
      accumulation in separate endosomes. EGFR showed downregulation between 15 min and
      2 h, whereas accumulation of alpha2beta1 integrin/EV1 led to an increase of
      integrin fluorescence in cytoplasmic vesicles further suggesting that EV1 pathway
      is separate from the lysosomal downregulation pathway. In addition, the results
      demonstrate the involvement of ESCRTs in the biogenesis of alpha2-MVBs.
      Overexpression of dominant-negative form of VPS4 inhibited biogenesis of alpha2
      MVBs and efficiently prevented EV1 infection. Furthermore, alpha2-MVBs were
      positive for some members of ESCRTs such as Hrs, VPS37A and VPS24 and the siRNA
      treatment of TSG101, VPS37A and VPS24 inhibited EV1 infection. Our results show
      that the non-enveloped EV1 depends on biogenesis of novel multivesicular
      structures for successful infection.

PMID- 21899699
TI  - Activation of cell stress response pathways by Shiga toxins.
AB  - Shiga toxin-producing bacteria cause widespread outbreaks of bloody diarrhoea
      that may progress to life-threatening systemic complications. Shiga toxins
      (Stxs), the main virulence factors expressed by the pathogens, are ribosome
      inactivating proteins which inhibit protein synthesis by removing an adenine
      residue from 28S rRNA. Recently, Stxs were shown to activate multiple stress
      associated signalling pathways in mammalian cells. The ribotoxic stress response
      is activated following the depurination reaction localized to the alpha
      sarcin/ricin loop of eukaryotic ribosomes. The unfolded protein response (UPR)
      may be initiated by toxin unfolding within the endoplasmic reticulum, and
      maintained by production of truncated, misfolded proteins following intoxication.
      Activation of the ribotoxic stress response leads to signalling through MAPK
      cascades, which appears to be critical for activation of innate immunity and
      regulation of apoptosis. Precise mechanisms linking ribosomal damage with MAPK
      activation require clarification but may involve recognition of ribosomal
      conformational changes and binding of protein kinases to ribosomes, which
      activate MAP3Ks and MAP2Ks. Stxs appear capable of activating all ER membrane
      localized UPR sensors. Prolonged signalling through the UPR induces apoptosis in
      some cell types. The characterization of stress responses activated by Stxs may
      identify targets for the development of interventional therapies to block cell
      damage and disease progression.

PMID- 21899701
TI  - Stage-specific depletion of myosin A supports an essential role in motility of
      malarial ookinetes.
AB  - Functional analysis of Plasmodium genes by classical reverse genetics is
      currently limited to mutants that are viable during erythrocytic schizogony, the
      pathogenic phase of the malaria parasite where transfection is performed. Here,
      we describe a conceptually simple experimental approach to study the function of
      genes essential to the asexual blood stages in a subsequent life cycle stage by a
      promoter-swap approach. As a proof of concept we targeted the unconventional
      class XIV myosin MyoA, which is known to be required for Toxoplasma gondii
      tachyzoite locomotion and host cell invasion. By placing the corresponding
      Plasmodium berghei gene, PbMyoA, under the control of the apical membrane antigen
      1 (AMA1) promoter, expression in blood stages is maintained but switched off
      during transmission to the insect vector, i.e. ookinetes. In those mutant
      ookinetes gliding motility is entirely abolished resulting in a complete block of
      life cycle progression in Anopheles mosquitoes. Similar approaches should permit
      the analysis of gene function in the mosquito forms that are shared with the
      erythrocytic stages of the malaria parasite.

PMID- 21899702
TI  - The ERM protein, ezrin, regulates neutrophil transmigration by modulating the
      apical localization of MRP2 in response to the SipA effector protein during
      Salmonella Typhimurium infection.
AB  - In human disease induced by Salmonella enterica serovar Typhimurium (S.
      Typhimurium), transepithelial migration of neutrophils rapidly follows attachment
      of the bacteria to the epithelial apical membrane. We have previously shown that
      during S. Typhimurium infection the multidrug resistance-associated protein 2
      (MRP2) is highly expressed at the apical surface of the intestinal epithelia, and
      that it functions as an efflux pump for the potent neutrophil chemoattractant
      hepoxilin A(3) . However, the molecular mechanisms regulating its apical
      localization during active states of inflammation remain unknown. Thus, our
      objective was to determine the mechanistic basis for the translocation of MRP2 to
      the apical surface of intestinal epithelial cells during S. Typhimurium
      infection. We show that suppression of ezrin, through either RNAi or truncation
      of the C-terminus, results not only in a decrease in S. Typhimurium-induced
      neutrophil transmigration but also significantly attenuates the apical membrane
      expression of MRP2 during Salmonella infection. In addition, we determined that
      S. Typhimurium induces the activation of ezrin via a PKC-alpha-dependent pathway
      and that ezrin activation is coupled to apical localization of MRP2. Based on
      these results we propose that activation of ezrin is required for the apical
      localization of MRP2 during S. Typhimurium infection.

PMID- 21899703
TI  - The Salmonella effector AvrA mediates bacterial intracellular survival during
      infection in vivo.
AB  - The enteric pathogen Salmonella typhimurium secretes the preformed AvrA effector
      protein into host cells. This acetyltransferase has been shown to modulate
      mammalian intestinal immune and survival responses by inhibition of JNK MAPK. To
      study the role of this effector in natural enteric infection, we used a mouse
      model to compare wild-type S. typhimurium to an isogenic AvrA null Salmonella
      mutant. Salmonella lacking AvrA induced increased intestinal inflammation, more
      intense systemic cytokine responses, and increased apoptosis in epithelial cells.
      Increased apoptosis was also observed in extra epithelial macrophages. AvrA null
      infected mice consistently showed higher bacterial burden within mucosal lymphoid
      tissues, spleen and liver by 5 days post infection, which indicated a more severe
      clinical course. To study the molecular mechanisms involved, recombinant
      adenoviruses expressing AvrA or mutant AvrA proteins were constructed, which
      showed appropriate expression and mediated the expected inhibition of JNK
      signalling. Cultured epithelial cells and macrophages transduced with AvrA
      expressing adenovirus were protected from apoptosis induced by exogenous stimuli.
      In conclusion, the results demonstrated that Salmonella AvrA modulates survival
      of infected macrophages likely via JNK suppression, and prevents macrophage death
      and rapid bacterial dissemination. AvrA suppression of apoptosis in infected
      macrophages may allow for establishment of a stable intracellular niche typical
      of intracellular pathogens.

PMID- 21899704
TI  - Involvement of suppressor of cytokine signalling-1-mediated degradation of MyD88
      adaptor-like protein in the suppression of Toll-like receptor 2-mediated
      signalling by the murine C-type lectin SIGNR1-mediated signalling.
AB  - Dendritic cells recognize pathogens through pattern recognition receptors such as
      Toll-like receptors and phagocytose and digest them by phagocytic receptors for
      antigen presentation. This study was designed to clarify the cross-talk between
      recognition and phagocytosis of microbes in dendritic cells. The murine dendritic
      cell line XS106 cells were stimulated with the murine C-type lectin SIGNR1 ligand
      lipoarabinomannan and the Toll-like receptor 2 ligand FSL-1. The co-stimulation
      significantly suppressed FSL-1-mediated activation of NF-kappaB as well as
      production of TNF-alpha, IL-6 and IL-12p40 in a dose-dependent manner. The
      suppression was significantly but not completely recovered by knock-down of
      SIGNR1. SIGNR1 was associated with Toll-like receptor 2 in XS106 cells. The co
      stimulation upregulated the expression of suppressor of cytokine signalling-1 in
      XS106 cells, the knock-down of which almost completely recovered the suppression
      of the FSL-1-mediated cytokine production by lipoarabinomannan. In addition, it
      was found that the MyD88-adaptor-like protein in XS106 cells was degraded by co
      stimulation with FSL-1 and lipoarabinomannan in the absence, but not the
      presence, of the proteasome inhibitor MG132 and the degradation was inhibited by
      knock-down of suppressor of cytokine signalling-1. This study suggests that Toll
      like receptor 2-mediated signalling is negatively regulated by SIGNR1-mediated
      signalling in dendritic cells, possibly through suppressor of cytokine signalling
      1-mediated degradation of the MyD88-adaptor-like protein.

PMID- 21899705
TI  - The Entamoeba histolytica methylated LINE-binding protein EhMLBP provides
      protection against heat shock.
AB  - Adaptation to environmental stress is a key process that allows the unicellular
      parasite Entamoeba histolytica to survive in its human host. We previously
      characterized EhMLBP as an essential protein for the growth and the virulence of
      the parasite. EhMLBP binds to methylated repetitive DNA, and is one of the core
      proteins of the parasite's epigenetic machinery. Here, we show that EhMLBP and
      heat shock proteins have common properties. EhMLBP is induced by heat shock and
      its expression is regulated by a heat shock element binding site that is located
      in its 5' non-coding region. Following heat shock, the perinuclear localization
      of EhMLBP in control trophozoites is replaced by an even distribution within the
      nucleus alongside with an enhanced recruitment of EhMLBP to the reverse
      transcriptase of a long interspersed nucleotide element (LINE) DNA. Constitutive
      overexpression of EhMLBP protects trophozoites against heat shock and reduces
      protein aggregation. This protective function is lost in trophozoites that
      overexpress a mutated form of EhMLBP which is devoid of its heat shock domain. To
      the best of our knowledge, this is the first report of a methyl DNA-binding
      protein that plays a protective role against heat shock.

PMID- 21899706
TI  - Laparoscopic restorative proctocolectomy: safety and critical level of the ileal
      pouch anal anastomosis.
AB  - AIM: The study reports the longer-term results of laparoscopic-assisted
      restorative proctocolectomy (RPC), with particular reference to safety and the
      level of the stapled ileal pouch-anal anastomosis (IPAA). METHOD: Data were
      collected prospectively from all patients who underwent laparoscopic RP from July
      2006 to July 2010. In each patient the operation involved the use of a short (6
      cm) Pfannenstiel incision to facilitate placement of the linear stapler for
      anorectal division. RESULTS: Seventy-five patients underwent RPC either with
      total proctocolectomy (n = 53) or after previous emergency colectomy (n = 22).
      Early postoperative morbidity occurred in 18 (24%) patients and readmission
      within 30 days occurred in 18 (24%). Morbidity during follow up developed in 29
      (39%). A pouchogram was carried out in all 75 patients before ileostomy closure
      with an abnormality shown in eight. The median level of the IPAA was at 3.0 cm
      (1.0-5.0 cm) above the dentate line. At a median of 33 (9-57) months, there has
      been one case of small bowel obstruction and no incisional hernia. CONCLUSION: In
      laparoscopic-assisted RPC a limited Pfannenstiel incision allows safe
      construction of the IPAA at an appropriate level. Laparoscopic RPC is safe and
      the emerging long-term follow-up data show the benefit of this approach, with
      very low rates of small bowel obstruction and incisional hernia formation.

PMID- 21899707
TI  - Infliximab and surgical treatment of complex anal Crohn's disease.
AB  - AIM: Perianal fistulae in Crohn's disease are frequently complex, involve the
      anal sphincter complex and surgical treatment can be associated with poor healing
      of wounds and damage to the mechanism of continence. The aim of this study was to
      evaluate the efficacy and duration of response to infliximab in the long-term
      management of perianal fistulae in Crohn's disease in routine clinical practice.
      METHOD: A prospectively maintained database was used to identify patients with
      Crohn's disease and complex anal fistulae who were treated with infliximab
      (primary treatment, three initial infusions followed by maintenance therapy).
      Patients who received infliximab for luminal disease or for enterocutaneous,
      peristomal or rectovaginal fistulae were excluded from this study. RESULTS: Fifty
      two patients [25 male, median age 24 (range 15-72) years] were treated with
      infliximab for perianal Crohn's fistulae for a median of 66 (7-124) months.
      Twenty-six of the patients underwent pre-infliximab MRI scans and 38 had an
      examination under anaesthetic (EUA) prior to commencement of treatment, 22 of
      whom had seton(s) inserted into their fistulae. Maintenance therapy was possible
      in 42 (81%) of 52 patients. Twenty-two (42.3%) patients had a complete response
      to treatment, 23 (44.2%) had a partial response and 7 (13.5%) had no response.
      Less than complete response to infliximab was associated with a greater risk of
      requiring surgical intervention (Fisher's exact test, d.f. 1, P = 0.005).
      CONCLUSION: The response rates of Crohn's related complex perianal fistulae to
      infliximab are good. Complete response is associated with a reduced need for
      surgical intervention.

PMID- 21899709
TI  - Current practice in preoperative therapy and surgical management of locally
      advanced rectal cancer: a bi-national survey.
AB  - AIM: The Australasian colorectal surgeon's current approach to preoperative
      rectal cancer management was compared with international guidelines. METHOD:
      Members of the Colorectal Surgical Society of Australia and New Zealand were
      surveyed in 2010, on the use of MRI and the management of locally advanced rectal
      cancer. Surgeons had to decide the appropriate management in five scenarios that
      were developed from national guidelines. RESULTS: Of 174 invitations sent, 108
      (62.1%) replies were received. Most surgeons (98.1%) had access to MRI. Ninety
      three (86.1%) would use MRI routinely for staging. The majority selected a tumour
      specific mesorectal resection for upper rectal cancer (58.2%) and a total
      mesorectal excision for distal cancer (100%). Almost all restorative operations
      included a covering ileostomy. One third of surgeons recommended that patients
      with a favourable cT3 mid-rectal tumour (N0, clear circumferential resection
      margins) should not have preoperative therapy and should proceed directly to
      surgery. When high-risk features, such as threatened resection margins or cN1
      stage, were present, 5% and 15% of surgeons, respectively, would continue to
      treat by standard resection without preoperative therapy. CONCLUSION: Evidence
      based international guidelines for the management of rectal cancer have changed
      little in the last 10 years. Despite this, there is a clear gap between these and
      clinical practice. The main variance relates to the role of radiotherapy in
      locally advanced rectal cancer. Despite considerable evidence that radiotherapy
      reduces local recurrence for all stages of rectal cancer, current practice in
      Australasia is for its selective use.

PMID- 21899708
TI  - No effect of perianal application of topical anaesthetic on patient comfort
      during nonsedated flexible sigmoidoscopy: a randomized, placebo-controlled
      clinical trial.
AB  - AIM: A literature review revealed no data on the effects of topical anaesthetic
      on patient comfort during flexible sigmoidoscopy. We therefore aimed to evaluate
      this in a randomized manner. METHOD: One hundred and forty-six patients who
      underwent flexible sigmoidoscopy were randomly allocated to one of three groups.
      Vaseline (n = 49), 2% lidocaine gel (n = 51) or a cream of 2.5% lidocaine plus
      2.5% prilocaine (n = 46) were applied to the patients 30 min before the
      procedure. Demographic data and haemodynamic monitoring during procedures were
      recorded. Pain was assessed by visual analogue scale (VAS) and anxiety levels by
      the State-Trait Anxiety Inventory (STAI-I and STA-II). RESULTS: Median pre
      procedural STAI-I scores were 45, 46 and 40.5 and median post-procedural STAI-I
      scores were 35, 34 and 33.5 for the vaseline, lidocaine, and lidocaine/prilocaine
      treatments, respectively. There was no statistical difference among the groups in
      terms of STAI-I and II scores. However, post-procedural STAI-I scores were
      significantly lower than pre-procedural values in each group (P < 0.001). There
      was no significant difference in VAS scores among the groups. In all groups there
      were statistically higher VAS scores during the procedure compared with the pre-
      and post-procedural scores (P < 0.001). CONCLUSION: Perianal application of
      topical anaesthetic does not influence patient comfort during sigmoidoscopy.

PMID- 21899710
TI  - [New information about fumaric acid esters (Fumaderm): results of a workshop of
      experts].

PMID- 21899711
TI  - Can acute abdominal CT prioritize patients with suspected diverticulitis for a
      subsequent clean colonic examination?
AB  - AIM: The aim of this study was to investigate whether patients with
      diverticulitis can be prioritized with higher urgency for a subsequent full
      colonic examination based upon the emergency abdominal CT scan performed at the
      time of presentation. METHOD: All patients with a diagnosis of diverticulitis,
      hospitalized during 2006 and having a CT scan on admission and a subsequent
      'clean colon' examination, were reviewed. The CT scan was reviewed by two
      independent and blinded senior radiologists (Radiologist A and Radiologist B) for
      signs inconsistent with diverticulitis and suggestive of malignancy. The patients
      were classified on the CT scan results into group 1 (normal findings, nontumour
      pathology or benign polyps < 1 cm) or group 2 (benign polyps >= 1 cm and cancer).
      RESULTS: Ninety-three patients (83 in group 1 and 10 in group 2) were reviewed.
      Radiologist A suggested high-priority colonic examination in 18% and 50% of
      patients in groups 1 and 2, respectively, and Radiologist B in 63% and 90% of
      patients, respectively. There was a statistically significant interobserver
      difference, and also lower accuracy of Radiologist B compared with Radiologist A
      in predicting a subsequent 'clean colon' examination. CONCLUSION: Use of an
      emergency acute CT scan at the time of diagnosis of diverticulitis to predict a
      clean colon examination for neoplasia is not reliable because there is a
      considerable degree of interobserver difference between radiologists.

PMID- 21899712
TI  - Initial results of a randomized controlled trial comparing clinical and
      pathological downstaging of rectal cancer after preoperative short-course
      radiotherapy or long-term chemoradiotherapy, both with delayed surgery.
AB  - AIM: The aim of this study was to compare the downstaging achieved after long
      course chemoradiotherapy (chRT) and short-term radiotherapy (sRT) followed by
      delayed surgery. METHOD: A randomized controlled trial was carried out. Eighty
      three patients with resectable stage II and III rectal adenocarcinoma were
      randomized to receive long-course chemoradiotherapy (46) and short-term
      radiotherapy (5*5 Gy) (37). Surgery was performed 6 weeks after preoperative
      treatment in both groups. RESULTS: The R0 resection rate was 91.3% in the chRT
      and 86.5% in the sRT group (P=0.734). Sphincter preservation rates were 69.6%vs
      70.3% (P=0.342) and postoperative complication rates were 26.1%vs 40.5%
      (P=0.221). There were more patients with early pT stage [pT0 (complete
      pathological response) pT1] in the chRT group [21.8%vs 2.7% (P=0.03)] and more
      patients with pT3 disease in the sRT group [75.7%vs 52.2% (P=0.036)]. There were
      no differences in pN stage and lymphatic or vascular invasion in either group.
      Pathological downstaging (stage 0 and I) was observed in eight (21.6%) patients
      in the sRT group and in 18 (39.1%) in the chRT group (P=0.07). Tumours were
      smaller after preoperative ChRT (2.5 cm vs 3.3 cm; P=0.04). CONCLUSION: Long
      course preoperative chemoradiation resulted in greater statistically significant
      tumour downsizing and downstaging compared with short-term radiation, but there
      was no difference in the R0 resection rates. Similar postoperative morbidity was
      observed in each group.

PMID- 21899714
TI  - Palliative excisional surgery for primary colorectal cancer in patients with
      incurable metastatic disease. Is there a survival benefit? A systematic review.
AB  - AIM: Patients with stage IV colorectal cancer with unresectable metastases can
      either receive chemotherapy or palliative resection of the primary lesion. In the
      absence of any randomized data the choice of initial treatment in stage IV
      colorectal cancer is not based on firm evidence. METHOD: A search of MEDLINE,
      Pubmed, Embase and the Cochrane Library database was performed from 1980 to 2010
      for studies comparing palliative resection in stage IV colorectal cancer with
      other treatment modalities. Audits and observational studies were excluded.
      Median survival was the primary outcome measure. The morbidity and mortality of
      surgical and nonsurgical treatments were compared. RESULTS: Twenty-one studies
      (no randomized controlled trials) were identified. Most demonstrated a survival
      benefit for patients who underwent palliative resection. Multivariate analysis
      indicates that tumour burden and performance status are both major independent
      prognostic variables. Selection bias, incomplete follow up and nonstandardized
      reporting of complications make the data difficult to interpret. CONCLUSION: The
      studies indicate that there may be a survival benefit for primary resection of
      colorectal cancer in stage IV disease. The findings suggest that resection of the
      primary tumour should be based on tumour burden and performance status rather
      than on the presence or absence of symptoms alone.

PMID- 21899713
TI  - The effect of ursodesoxycholic acid on duodenal adenomas in familial adenomatous
      polyposis: a prospective randomized placebo-control trial.
AB  - AIM: Duodenal adenomas occur in about 90% of patients with familial adenomatous
      polyposis (FAP) and are the second cause of death of patients who have had a
      prophylactic proctocolectomy. Studies suggest that biliary acids have a role in
      the development of duodenal adenomas. The aim of this study was to evaluate the
      impact of ursodesoxycholic acid (UDCA) on duodenal adenoma formation in patients
      with FAP. METHOD: A randomized, double-blinded, placebo-controlled study was
      carried out of 71 patients (20-65 years) who already had a restorative
      proctocolectomy. Subjects received either 10 mg/kg of UDCA orally per day or a
      placebo tablet for 24 months. The Spigelman severity score was determined after
      duodenal axial and lateral view endoscopy at 12 and 24 months. RESULTS: At 2
      years 55 patients had completed the entire period of treatment. At the end of the
      follow-up period, nine (25%) patients in the UDCA group and seven (20%) in the
      placebo group had a decrease in the Spigelman score (P = 0.6142). Patients
      receiving UDCA had no side-effects (0%) compared with four (14%) in the placebo
      group (P = 0.0392). CONCLUSION: UDCA had no effect on the development of duodenal
      adenomas in FAP patients (NCT: 00134758).

PMID- 21899715
TI  - Patterns and correlates of prescription opioid use in OEF/OIF veterans with
      chronic noncancer pain.
AB  - OBJECTIVES: Little is known about the treatment Operation Enduring
      Freedom/Operation Iraqi Freedom (OEF/OIF) veterans receive for chronic noncancer
      pain (CNCP). We sought to describe the prevalence of prescription opioid use,
      types, and doses of opioids received and to identify correlates of receiving
      prescription opioids for CNCP among OEF/OIF veterans. DESIGN: Retrospective
      review of Veterans Affairs (VA) administrative data. SETTING: Ambulatory clinics
      within a VA regional health care network. PATIENTS: OEF/OIF veterans who had at
      least three elevated pain screening scores within a 12-month period in 2008.
      Within this group, those prescribed opioids (N = 485) over the next 12 months
      were compared with those not prescribed opioids (N = 277). In addition, patients
      receiving opioids short term (<90 days, N = 284) were compared with patients
      receiving them long term (>=90 consecutive days, N = 201). RESULTS: Of 762
      OEF/OIF veterans with CNCP, 64% were prescribed at least one opioid medication
      over the 12 months following their index dates. Of those prescribed an opioid,
      59% were prescribed opioids short term and 41% were prescribed opioids long term.
      The average morphine-equivalent opioid dose for short-term users was 23.7 mg
      (standard deviation [SD] = 20.5) compared with 40.8 mg (SD = 36.1) for long-term
      users (P < 0.001). Fifty-one percent of long-term opioid users were prescribed
      short-acting opioids only, and one-third were also prescribed sedative hypnotics.
      In adjusted analyses, diagnoses of low back pain, migraine headache,
      posttraumatic stress disorder, and nicotine use disorder were associated with an
      increased likelihood of receiving an opioid prescription. CONCLUSION:
      Prescription opioid use is common among OEF/OIF veterans with CNCP and is
      associated with several pain diagnoses and medical conditions.

PMID- 21899716
TI  - The influence of Chinook winds and other weather patterns upon neuropathic pain.
AB  - OBJECTIVE: Although Chinook winds are often viewed positively during a cold
      prairie winter, patients suffering with neuropathic pain (NeP) anecdotally report
      exacerbations of NeP during Chinooks and during other weather changes. Our
      objective was to identify if Chinook winds lead to acute exacerbations in pain
      severity in a NeP patient population. DESIGN: Prospective diary-based assessments
      of patients with at least moderate NeP over 6-month periods during different
      seasons of the year were performed. Concurrent weather conditions were tracked
      hourly, with Chinook winds defined using accepted meteorological definition. We
      also examined other aspects of weather including precipitation, temperature, and
      humidity. Days with acute exacerbations were defined when a daily visual analog
      score pain score was >=2 points above their average NeP score over the entire 6
      month period. RESULTS: Chinooks were not associated with individual acute
      exacerbations in NeP. Instead, Chinook days were found to be protective against
      acute exacerbations in NeP (odds ratio 0.52 [0.33-0.71]). Post hoc study
      associated Chinooks with NeP relief (odds ratio 1.83 [1.17-2.49]). We could not
      identify relationship between precipitation or humidity with acute NeP
      exacerbation. However, days with cold temperature <= -14 degrees C were
      associated with greater risk of NeP exacerbation. CONCLUSION: Weather-mediated
      changes occur for patients with NeP, manifesting as relief from Chinook winds
      while cold temperature conditions can provoke exacerbations in NeP.

PMID- 21899717
TI  - Use of machine learning theory to predict the need for femoral nerve block
      following ACL repair.
AB  - OBJECTIVE: We report on a classification approach using machine learning (ML)
      algorithms for prediction of postoperative femoral nerve block (FNB) requirement
      following anterior cruciate ligament (ACL) reconstruction. BACKGROUND: FNBs are
      commonly performed for ACL reconstruction to control postoperative pain. Ideally,
      anesthesiologists would target preoperative FNB only to ACL reconstruction
      patients expected to experience severe postoperative pain. Perioperative factors
      associated with postoperative FNB placement following ACL reconstruction remain
      unclear, may differ among separate surgical facilities, and render such
      predictions difficult. METHODS: We conducted a chart review of 349 patients who
      underwent ACL reconstruction at a single outpatient surgical facility. Standard
      perioperative data commonly available during routine preoperative examination
      were recorded. ML classifiers based on logistic regression, BayesNet, multilayer
      perceptron, support vector machine, and alternating decision tree (ADTree)
      algorithms were then developed to predict which patients would require
      postoperative FNB. RESULTS: Each of the ML algorithms outperformed traditional
      logistic regression using a very limited data set as measured by the area under
      the receiver operating curve, with ADTree achieving the highest score of 0.7 in
      the cross-validated sample. Logistic regression outperformed all other
      classifiers with regard to kappa statistics and percent correctly classified. All
      models were prone to overfitting in comparisons of training vs cross-validated
      samples. CONCLUSION: ML classifiers may offer improved predictive capabilities
      when analyzing medical data sets compared with traditional statistical
      methodologies in predicting severe postoperative pain requiring peripheral nerve
      block.

PMID- 21899719
TI  - Comparison of time within therapeutic INR range with percentage INR within
      therapeutic range for assessing long-term anticoagulation control in children:
      reply to a rebuttal.

PMID- 21899718
TI  - Predictors of pain medication selection among patients diagnosed with
      fibromyalgia.
AB  - OBJECTIVES: Several pharmacologic therapies have been recommended for managing
      fibromyalgia. However, the factors associated with each treatment initiation have
      not been well established. This study assessed factors that were associated with
      the use of duloxetine vs. other pain medications among patients with
      fibromyalgia. RESEARCH DESIGN AND METHODS: Administrative claims from a large,
      U.S. commercially insured population were analyzed using a retrospective cohort
      design. Patients with fibromyalgia who were 18 to 64 years old and initiated
      duloxetine vs. selective serotonin reuptake inhibitors (SSRIs), tricyclic
      antidepressants (TCAs), venlafaxine, gabapentin, pregabalin, tramadol, or
      nontramadol opioids between January 1, 2007 and December 12, 2008 were selected.
      Treatment initiation was defined as no access to the same medication over the
      previous 90 days, with the most recent initiation date as the index date. All
      patients selected had at least one fibromyalgia diagnosis (ICD-9-CM: 729.1) in
      the 12 months prior to initiation of each study medication. Multiple logistic
      regression models were estimated to assess the predictors of initiating
      duloxetine vs. each of the other medications. RESULTS: The study included 117,305
      patients with fibromyalgia (48 years of age on average; 76% women) who initiated
      duloxetine (n = 5,827), SSRIs (n = 8,620), TCAs (n = 5,424), venlafaxine (n =
      2,038), gabapentin (n = 5,733), pregabalin (n = 11,152), tramadol (n = 7,312), or
      nontramadol opioids (n = 71,199). Common fibromyalgia-related comorbidities were
      low back pain (31% to 49%), osteoarthritis (14% to 21%), and sleep disturbance
      (10% to 15%). Controlling for demographic and clinical characteristics, patients
      who received pregabalin in the prior 12-month period were more likely to initiate
      duloxetine. Patients from other treatment cohorts, except for those in the
      pregabalin and nontramadol opioid cohorts, were more likely to re-initiate the
      same prior medication than to begin treatment with duloxetine. Other predictors
      of duloxetine initiation included history of rheumatoid and sleep disturbance.
      CONCLUSIONS: The presence of select comorbidities and prior use of certain
      medications were associated with the duloxetine initiation among working-age,
      commercially insured patients with fibromyalgia.

PMID- 21899720
TI  - Relaxin-3 null mutation mice display a circadian hypoactivity phenotype.
AB  - Characterizing the neurocircuits and neurotransmitters that underlie arousal and
      circadian sleep/wake patterns is an important goal of neuroscience research, with
      potential implications for understanding human mental illnesses, such as major
      depression. Recent anatomical and functional studies suggest that relaxin-3
      neurons and their ascending projections contribute to these functions via actions
      on key cortical, limbic and hypothalamic circuits. This study reports the
      behavioral phenotype of C57BL/6J backcrossed relaxin-3 knockout (KO) mice.
      Cohorts of adult, male and female relaxin-3 KO and wild-type (WT) littermate mice
      were subjected to a battery of behavioral tests to assess sensorimotor function
      and complex behavior. No overt deficits were detected in motor-coordination,
      spatial memory, sensorimotor gating, anxiety-like behavior or locomotor behavior
      in novel environments; and no marked genotype differences were observed in
      response to a chronic stress protocol. Notably however, compared to WT mice,
      relaxin-3 KO mice displayed robust hypoactivity during the dark/active phase when
      provided with free home-cage access to voluntary running wheels. This circadian
      hypoactivity was reflected by reduced time spent and distance traveled on running
      wheels, coupled with an increase in the time spent immobile, possibly reflecting
      increased sleeping. Overall, these studies support a role for relaxin-3 signaling
      in the control of arousal and sleep/wakefulness, and identify the relaxin-3 KO
      mouse as a useful model to study this role further.

PMID- 21899721
TI  - Cutaneous malakoplakia.

PMID- 21899722
TI  - Comment on 'Birdstrikes and barcoding: can DNA methods help make the airways
      safer?'.
AB  - GenBank is the database of record for public sequence data. Results reported in
      the scientific literature that are based on sequence data cannot be evaluated if
      the underlying data is not in the public record.

PMID- 21899723
TI  - JML: testing hybridization from species trees.
AB  - I introduce the software JML that tests for the presence of hybridization in
      multispecies sequence data sets by posterior predictive checking following Joly,
      McLenachan and Lockhart (2009, American Naturalist 174, e54). Although their
      method could potentially be applied on any data set, the lack of appropriate
      software made its application difficult. The software JML thus fills a need for
      an easy application of the method but also includes improvements such as the
      possibility to incorporate uncertainty in the species tree topology. The JML
      software uses a posterior distribution of species trees, population sizes and
      branch lengths to simulate replicate sequence data sets using the coalescent with
      no migration. A test quantity, defined as the minimum pairwise sequence distance
      between sequences of two species, is then evaluated on the simulated data sets
      and compared to the one estimated from the original data. Because the test
      quantity is a good predictor of hybridization events, departure from the
      bifurcating species tree model could be interpreted as evidence of hybridization.
      Software performance in terms of computing time is evaluated for several
      parameters. I also show an application example of the software for detecting
      hybridization among native diploid North American roses.

PMID- 21899726
TI  - Sorting through the many opportunities for melanoma therapy.

PMID- 21899729
TI  - Treatment of imported severe malaria with artesunate instead of quinine--more
      evidence needed?
AB  - Rapid and fast acting anti-malarials are essential to treat severe malaria.
      Quinine has been the only option for parenteral therapy until recently. While
      current evidence shows that intravenous artesunate is more effective than quinine
      in treating severe malaria in endemic countries, some questions remain regarding
      safety profiles and drug resistance. For imported severe malaria, additional
      unanswered questions are related to generalizability of the findings from endemic
      countries and to legal aspects, as there is no Good Manufacturing Practice
      conform drug available yet. Here, the implications of existing evidence for the
      treatment of imported severe malaria are discussed.

PMID- 21899728
TI  - c-Myc dependent expression of pro-apoptotic Bim renders HER2-overexpressing
      breast cancer cells dependent on anti-apoptotic Mcl-1.
AB  - BACKGROUND: Anti-apoptotic signals induced downstream of HER2 are known to
      contribute to the resistance to current treatments of breast cancer cells that
      overexpress this member of the EGFR family. Whether or not some of these signals
      are also involved in tumor maintenance by counteracting constitutive death
      signals is much less understood. To address this, we investigated what role anti-
      and pro-apoptotic Bcl-2 family members, key regulators of cancer cell survival,
      might play in the viability of HER2 overexpressing breast cancer cells. METHODS:
      We used cell lines as an in vitro model of HER2-overexpressing cells in order to
      evaluate how anti-apoptotic Bcl-2, Bcl-xL and Mcl-1, and pro-apoptotic Puma and
      Bim impact on their survival, and to investigate how the constitutive expression
      of these proteins is regulated. Expression of the proteins of interest was
      confirmed using lysates from HER2-overexpressing tumors and through analysis of
      publicly available RNA expression data. RESULTS: We show that the depletion of
      Mcl-1 is sufficient to induce apoptosis in HER2-overexpressing breast cancer
      cells. This Mcl-1 dependence is due to Bim expression and it directly results
      from oncogenic signaling, as depletion of the oncoprotein c-Myc, which occupies
      regions of the Bim promoter as evaluated in ChIP assays, decreases Bim levels and
      mitigates Mcl-1 dependence. Consistently, a reduction of c-Myc expression by
      inhibition of mTORC1 activity abrogates occupancy of the Bim promoter by c-Myc,
      decreases Bim expression and promotes tolerance to Mcl-1 depletion. Western blot
      analysis confirms that naive HER2-overexpressing tumors constitutively express
      detectable levels of Mcl-1 and Bim, while expression data hint on enrichment for
      Mcl-1 transcripts in these tumors. CONCLUSIONS: This work establishes that, in
      HER2-overexpressing tumors, it is necessary, and maybe sufficient, to
      therapeutically impact on the Mcl-1/Bim balance for efficient induction of cancer
      cell death.

PMID- 21899727
TI  - State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in
      the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS).
AB  - PCOS, a heterogeneous disorder characterized by cystic ovarian morphology,
      androgen excess, and/or irregular periods, emerges during or shortly after
      puberty. Peri- and post-pubertal obesity, insulin resistance and consequent
      hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an
      ongoing state of excess androgen. Given the relationship of insulin to androgen
      excess, reduction of insulin secretion and/or improvement of its action at target
      tissues offer the possibility of improving the physical stigmata of androgen
      excess by correction of the reproductive dysfunction and preventing metabolic
      derangements from becoming entrenched. While lifestyle changes that concentrate
      on behavioral, dietary and exercise regimens should be considered as first line
      therapy for weight reduction and normalization of insulin levels in adolescents
      with PCOS, several therapeutic options are available and in wide use, including
      oral contraceptives, metformin, thiazolidenediones and spironolactone.
      Overwhelmingly, the data on the safety and efficacy of these medications derive
      from the adult PCOS literature. Despite the paucity of randomized control trials
      to adequately evaluate these modalities in adolescents, their use, particularly
      that of metformin, has gained popularity in the pediatric endocrine community. In
      this article, we present an overview of the use of insulin sensitizing
      medications in PCOS and review both the adult and (where available) adolescent
      literature, focusing specifically on the use of metformin in both mono- and
      combination therapy.

PMID- 21899730
TI  - Recent increase of genetic diversity in Plasmodium vivax population in the
      Republic of Korea.
AB  - BACKGROUND: The reemergence of Plasmodium vivax in South Korea since 1993
      represents a serious public health concern. Despite the importance in
      understanding genetic diversity for control strategies, however, studies remain
      inconclusive with the general premise that due to low rate of malaria
      transmission, there is generally low genetic diversity with very few strains
      involved. In this study, the genetic diversity and population structure of P.
      vivax in South Korea were explored by analysing microsatellite polymorphism.
      METHODS: Sequences for 13 microsatellite loci distributed across the twelve
      chromosomes of P. vivax were obtained from 58 South Korean isolates collected
      during two sampling periods, namely 1997-2000 and 2007. The sequences were used
      for the analysis of expected heterozygosity and multilocus genotype diversity.
      Population structure was evaluated using STRUCTURE version 2.3.2. Linkage
      disequilibrium was also analysed to investigate the extent of outbreeding in the
      P. vivax population. RESULTS: Mean expected heterozygosity significantly
      increased from 0.382 in 1997-2000 to 0.545 in 2007 (P < 0.05). The number of
      multilocus genotypes was 7 and 27; and genotype diversity was statistically
      significant (P < 0.01) at 0.661 and 0.995 in 1997-2000 and 2007, respectively.
      Analysis by STRUCTURE showed a more complex population structure in 2007 than in
      1997-2000. Linkage disequilibrium between 13 microsatellites, although
      significant in both time points, was notably lower in 2007. CONCLUSIONS: The
      present microsatellite analysis clearly showed recent increase of genetic
      diversity and recent relaxation of the strong population structure observed in
      1997-2000. These results suggest that multiple genotypes not present previously
      recently migrated into South Korea, accompanied by substantial outbreeding
      between different genotypes.

PMID- 21899731
TI  - Malaria and pre-eclampsia in an area with unstable malaria transmission in
      Central Sudan.
AB  - BACKGROUND: Placental malaria and pre-eclampsia occur frequently in women in
      tropics and are leading causes of maternal and perinatal morbidities and
      mortality. Few data exist concerning the interaction between placental malaria
      and pre-eclampsia. METHODS: A case control study was conducted in Medani
      Hospital, which locates in an area of unstable malaria transmission in Central
      Sudan. Case (N = 143) were women with pre-eclampsia, which was defined as
      systolic blood pressure >= 140 mm Hg or diastolic blood pressure >= 90 mm Hg and
      proteinuria. Controls were parturient women (N = 143) without any blood pressure
      values > 139/89 mm Hg or proteinuria. Obstetrical and medical characteristics
      were gathered from both groups through structured questionnaires. Placental
      histopathology examinations for malaria were performed. RESULTS: Twenty-eight
      (19.6%) vs. 16 (11.2%); P = 0.04 of the cases vs. controls, had placental malaria
      infections. Five (2%), 1 (2%) and 22 (28.0%) vs. 1, 2 and 13 of the placentae
      showed acute, chronic and past infection on histopathology examination in the two
      groups respectively, while 115 (80.4%) vs.127 (88.8%) of them showed no
      infection, P = 0.04. In multivariate analysis, while there were no associations
      between age, parity, educational level, lack of antenatal care, blood groups and
      body mass index and pre-eclampsia; family history of hypertension and placental
      malaria (OR = 2.3, 95% CI = 1.0-5.2; P = 0.04) were significantly associated with
      pre-eclampsia. CONCLUSION: Placental malaria was associated with pre-eclampsia.
      Further research is needed.

PMID- 21899732
TI  - The role of common variants of the cholesteryl ester transfer protein gene in
      left main coronary artery disease.
AB  - BACKGROUND: The cholesteryl ester transfer protein (CETP) has a central role in
      the lipid metabolism and therefore may alter the susceptibility to
      atherosclerosis. METHODS: The DNA of 471 subjects [133 subjects with
      angiographically documented left main coronary artery disease (LMCAD), 241
      subjects with more peripheral coronary artery disease (MPCAD) and 97 subjects
      self reported healthy (Controls)] was analyzed for the frequency of TaqIB and
      I405V polymorphisms in the gene coding CETP. RESULTS: There is no significant
      difference in CETP allele frequency or genotype distribution among LMCAD and
      MPCAD patients although there is statistical difference between LMCAD and
      Controls (p = 0.001). Specifically, patients with LMCAD and B1B1 genotype of
      TaqIB polymorphism were more frequent present compared to Controls (33.8% vs
      22.9%, respectively). The frequency of B2B2 genotype was 3 times lower in the
      LMCAD group compared to Controls (10.5% vs 30.2%, respectively). In the LMCAD
      group the frequency of B1 allele compared to Controls was higher (62% vs 46%,
      respectively, p = 0.001). The relationship between TaqIB gene polymorphism and
      the LMCAD was independent of lipid profile, with the exception of apolipoprotein
      A. CONCLUSIONS: These findings indicate that the TaqIB polymorphism may have
      potential importance in screening individuals at high risk for developing CAD.
      However, this polymorphism cannot distinguish between LMCAD and MPCAD. Further
      prospective investigations in larger populations are required to confirm these
      findings.

PMID- 21899733
TI  - A multi-nutrient supplement reduced markers of inflammation and improved physical
      performance in active individuals of middle to older age: a randomized, double
      blind, placebo-controlled study.
AB  - BACKGROUND: While exercise acts to combat inflammation and aging, the ability to
      exercise may itself be compromised by inflammation and inflammation's impact on
      muscle recovery and joint inflammation. A number of nutritional supplements have
      been shown to reduce inflammation and improve recovery. The purpose of the
      current investigation was to examine the effect of a multi-nutrient supplement
      containing branched chain amino acids, taurine, anti-inflammatory plant extracts,
      and B vitamins on inflammatory status, endothelial function, physical function,
      and mood in middle-aged individuals. METHODS: Thirty-one healthy and active men
      (N = 16, mean age 56 +/- 6.0 yrs) and women (N = 15, mean age = 52 +/- 7.5 yrs)
      participated in this investigation. Subjects completed one 28 day cycle of
      placebo supplementation and one 28 day cycle of multi-nutrient supplementation
      (separated by a one week washout period) in a balanced, randomized, double-blind,
      cross-over design. Subjects completed weekly perceptual logs (PROMIS-57, KOOS)
      and pre- and post- testing around the supplementation period. Testing consisted
      of brachial artery flow mediated dilation (FMD), blood measures, and physical
      performance on vertical jump, handgrip strength, and balance (dispersion from
      center of pressure). Significance for the investigation was p <= 0.05. RESULTS:
      IL-6 significantly decreased in both men (from 1.2 +/- 0.2 to 0.7 +/- 0.4 pg.mL(
      1)) and women (from 1.16 +/- 0.04 to 0.7 +/- 0.4 pg.mL(-1)). Perceived energy
      also improved for both men (placebo: 1.8 +/- 0.7; supplement: 3.7 +/- 0.8 AUC)
      and women (placebo: 1.2 +/- 0.7; supplement: 2.8 +/- 0.8 AUC). Alpha-1
      antichymotrypsin (from 108.9 +/- 38.6 to 55.5 +/- 22.2 ug.mL(-1)), Creatine
      Kinase (from 96 +/- 34 to 67 +/- 23 IU.L(-1)), general pain, and joint pain
      decreased in men only, while anxiety and balance (from 0.52 +/- 0.13 to 0.45 +/-
      0.12 cm) improved in women only. Men showed increased performance in vertical
      jump power (from 2642 +/- 244 to 3134 +/- 282 W) and grip strength (from 42.1 +/-
      5.9 to 48.5 +/- 4.9 kg). CONCLUSIONS: A multi-nutrient supplement is effective in
      improving inflammatory status in both men and women, markers of pain, joint pain,
      strength, and power in men only, and both anxiety and balance (a risk factor for
      hip fracture) in women. Therefore, a multi-nutrient supplement may help middle
      aged individuals to prolong physical function and maintain a healthy, active
      lifestyle.

PMID- 21899734
TI  - Proteomics study of changes in soybean lines resistant and sensitive to
      Phytophthora sojae.
AB  - BACKGROUND: Phytophthora sojae causes soybean root and stem rot, resulting in an
      annual loss of 1-2 billion US dollars in soybean production worldwide. A
      proteomic technique was used to determine the effects on soybean hypocotyls of
      infection with P. sojae. RESULTS: In the present study, 46 differentially
      expressed proteins were identified in soybean hypocotyls infected with P. sojae,
      using two-dimensional electrophoresis and matrix-assisted laser
      desorption/ionization tandem time of flight (MALDI-TOF/TOF). The expression
      levels of 26 proteins were significantly affected at various time points in the
      tolerant soybean line, Yudou25, (12 up-regulated and 14 down-regulated). In
      contrast, in the sensitive soybean line, NG6255, only 20 proteins were
      significantly affected (11 up-regulated and 9 down-regulated). Among these
      proteins, 26% were related to energy regulation, 15% to protein destination and
      storage, 11% to defense against disease, 11% to metabolism, 9% to protein
      synthesis, 4% to secondary metabolism, and 24% were of unknown function.
      CONCLUSION: Our study provides important information on the use of proteomic
      methods for studying protein regulation during plant-oomycete interactions.

PMID- 21899736
TI  - Leucine supplementation improves adiponectin and total cholesterol concentrations
      despite the lack of changes in adiposity or glucose homeostasis in rats
      previously exposed to a high-fat diet.
AB  - BACKGROUND: Studies suggest that leucine supplementation (LS) has a therapeutic
      potential to prevent obesity and to promote glucose homeostasis. Furthermore,
      regular physical exercise is a widely accepted strategy for body weight
      maintenance and also for the prevention of obesity. The aim of this study was to
      determine the effect of chronic LS alone or combined with endurance training (ET)
      as potential approaches for reversing the insulin resistance and obesity induced
      by a high-fat diet (HFD) in rats. METHODS: Forty-seven rats were randomly divided
      into two groups. Animals were fed a control diet-low fat (n = 10) or HFD (n =
      37). After 15 weeks on HFD, all rats received the control diet-low fat and were
      randomly divided according to treatment: reference (REF), LS, ET, and LS+ET (n =
      7-8 rats per group). After 6 weeks of treatment, the animals were sacrificed and
      body composition, fat cell volume, and serum concentrations of total cholesterol,
      HDL-cholesterol, triacylglycerol, glucose, adiponectin, leptin and tumor necrosis
      factor-alpha (TNF-alpha) were analyzed. RESULTS: At the end of the sixth week of
      treatment, there was no significant difference in body weight between the REF,
      LS, ET and LS+ET groups. However, ET increased lean body mass in rats (P =
      0.019). In addition, ET was more effective than LS in reducing adiposity (P =
      0.019), serum insulin (P = 0.022) and TNF-alpha (P = 0.044). Conversely, LS
      increased serum adiponectin (P = 0.021) levels and reduced serum total
      cholesterol concentration (P = 0.042). CONCLUSIONS: The results showed that LS
      had no beneficial effects on insulin sensitivity or adiposity in previously obese
      rats. On the other hand, LS was effective in increasing adiponectin levels and in
      reducing total cholesterol concentration.

PMID- 21899735
TI  - Osteoarthritis accelerates and exacerbates Alzheimer's disease pathology in mice.
AB  - BACKGROUND: The purpose of this study was to investigate whether localized
      peripheral inflammation, such as osteoarthritis, contributes to neuroinflammation
      and neurodegenerative disease in vivo. METHODS: We employed the inducible Col1
      IL1betaXAT mouse model of osteoarthritis, in which induction of osteoarthritis in
      the knees and temporomandibular joints resulted in astrocyte and microglial
      activation in the brain, accompanied by upregulation of inflammation-related gene
      expression. The biological significance of the link between peripheral and brain
      inflammation was explored in the APP/PS1 mouse model of Alzheimer's disease (AD)
      whereby osteoarthritis resulted in neuroinflammation as well as exacerbation and
      acceleration of AD pathology. RESULTS: Induction of osteoarthritis exacerbated
      and accelerated the development of neuroinflammation, as assessed by glial cell
      activation and quantification of inflammation-related mRNAs, as well as Abeta
      pathology, assessed by the number and size of amyloid plaques, in the APP/PS1;
      Col1-IL1betaXAT compound transgenic mouse. CONCLUSION: This work supports a model
      by which peripheral inflammation triggers the development of neuroinflammation
      and subsequently the induction of AD pathology. Better understanding of the link
      between peripheral localized inflammation, whether in the form of osteoarthritis,
      atherosclerosis or other conditions, and brain inflammation, may prove critical
      to our understanding of the pathophysiology of disorders such as Alzheimer's,
      Parkinson's and other neurodegenerative diseases.

PMID- 21899737
TI  - Mimivirus reveals Mre11/Rad50 fusion proteins with a sporadic distribution in
      eukaryotes, bacteria, viruses and plasmids.
AB  - BACKGROUND: The Mre11/Rad50 complex and the homologous SbcD/SbcC complex in
      bacteria play crucial roles in the metabolism of DNA double-strand breaks,
      including DNA repair, genome replication, homologous recombination and non
      homologous end-joining in cellular life forms and viruses. Here we investigated
      the amino acid sequence of the Mimivirus R555 gene product, originally annotated
      as a Rad50 homolog, and later shown to have close homologs in marine microbial
      metagenomes. RESULTS: Our bioinformatics analysis revealed that R555 protein
      sequence is constituted from the fusion of an N-terminal Mre11-like domain with a
      C-terminal Rad50-like domain. A systematic database search revealed twelve
      additional cases of Mre11/Rad50 (or SbcD/SbcC) fusions in a wide variety of
      unrelated organisms including unicellular and multicellular eukaryotes, the
      megaplasmid of a bacterium associated to deep-sea hydrothermal vents
      (Deferribacter desulfuricans) and the plasmid of Clostridium kluyveri. We also
      showed that R555 homologs are abundant in the metagenomes from different aquatic
      environments and that they most likely belong to aquatic viruses. The observed
      phyletic distribution of these fusion proteins suggests their recurrent creation
      and lateral gene transfers across organisms. CONCLUSIONS: The existence of the
      fused version of protein sequences is consistent with known functional
      interactions between Mre11 and Rad50, and the gene fusion probably enhanced the
      opportunity for lateral transfer. The abundance of the Mre11/Rad50 fusion genes
      in viral metagenomes and their sporadic phyletic distribution in cellular
      organisms suggest that viruses, plasmids and transposons played a crucial role in
      the formation of the fusion proteins and their propagation into cellular genomes.

PMID- 21899738
TI  - Lentviral-mediated RNAi to inhibit target gene expression of the porcine integrin
      alphav subunit, the FMDV receptor, and against FMDV infection in PK-15 cells.
AB  - BACKGROUND: shRNA targeting the integrin alphav subunit, which is the foot-and
      mouth disease virus (FMDV) receptor, plays a key role in virus attachment to
      susceptible cells. We constructed a RNAi lentiviral vector, ialphav pLenti6/BLOCK
      -iTTM, which expressed siRNA targeting the FMDV receptor, the porcine integrin
      alphav subunit, on PK-15 cells. We also produced a lentiviral stock, established
      an ialphav-PK-15 cell line, evaluated the gene silencing efficiency of mRNA using
      real-time qRT-PCR, integrand alphav expression by indirect immunofluorescence
      assay (IIF) and cell enzyme linked immunosorbent assays (cell ELISA), and
      investigated the in vivo inhibitory effect of shRNA on FMDV replication in PK-15
      cells. RESULTS: Our results indicated successful establishment of the ialphav U6
      RNAi entry vector and the ialphav pLenti6/BLOCK -iT expression vector. The
      functional titer of obtained virus was 1.0 * 10(6) TU/mL. To compare with the
      control and mock group, the ialphav-PK-15 group alphav mRNA expression rate in
      group was reduced by 89.5%, whilst IIF and cell ELISA clearly indicated
      suppression in the experimental group. Thus, ialphav-PK-15 cells could reduce
      virus growth by more than three-fold and there was a > 99% reduction in virus
      titer when cells were challenged with 10(2) TCID(50) of FMDV. CONCLUSIONS:
      Ialphav-PK-15 cells were demonstrated as a cell model for anti-FMDV potency
      testing, and this study suggests that shRNA could be a viable therapeutic
      approach for controlling the severity of FMD infection and spread.

PMID- 21899739
TI  - Heterologous prime-boost-boost immunisation of Chinese cynomolgus macaques using
      DNA and recombinant poxvirus vectors expressing HIV-1 virus-like particles.
AB  - BACKGROUND: There is renewed interest in the development of poxvirus vector-based
      HIV vaccines due to the protective effect observed with repeated recombinant
      canarypox priming with gp120 boosting in the recent Thai placebo-controlled
      trial. This study sought to investigate whether a heterologous prime-boost-boost
      vaccine regimen in Chinese cynomolgus macaques with a DNA vaccine and recombinant
      poxviral vectors expressing HIV virus-like particles bearing envelopes derived
      from the most prevalent clades circulating in sub-Saharan Africa, focused the
      antibody response to shared neutralising epitopes. METHODS: Three Chinese
      cynomolgus macaques were immunised via intramuscular injections using a regimen
      composed of a prime with two DNA vaccines expressing clade A Env/clade B Gag
      followed by boosting with recombinant fowlpox virus expressing HIV-1 clade D Gag,
      Env and cholera toxin B subunit followed by the final boost with recombinant
      modified vaccinia virus Ankara expressing HIV-1 clade C Env, Gag and human
      complement protein C3d. We measured the macaque serum antibody responses by
      ELISA, enumerated T cell responses by IFN-gamma ELISpot and assessed
      seroneutralisation of HIV-1 using the TZM-bl beta-galactosidase assay with
      primary isolates of HIV-1. RESULTS: This study shows that large and complex
      synthetic DNA sequences can be successfully cloned in a single step into two
      poxvirus vectors: MVA and FPV and the recombinant poxviruses could be grown to
      high titres. The vaccine candidates showed appropriate expression of recombinant
      proteins with the formation of authentic HIV virus-like particles seen on
      transmission electron microscopy. In addition the b12 epitope was shown to be
      held in common by the vaccine candidates using confocal immunofluorescent
      microscopy. The vaccine candidates were safely administered to Chinese cynomolgus
      macaques which elicited modest T cell responses at the end of the study but only
      one out of the three macaques elicited an HIV-specific antibody response.
      However, the antibodies did not neutralise primary isolates of HIV-1 or the V3
      sensitive isolate SF162 using the TZM-bl beta-galactosidase assay. CONCLUSIONS:
      MVA and FP9 are ideal replication-deficient viral vectors for HIV-1 vaccines due
      to their excellent safety profile for use in humans. This study shows this novel
      prime-boost-boost regimen was poorly immunogenic in Chinese cynomolgus macaques.

PMID- 21899740
TI  - Characterization of a ViI-like phage specific to Escherichia coli O157:H7.
AB  - Phage vB_EcoM_CBA120 (CBA120), isolated against Escherichia coli O157:H7 from a
      cattle feedlot, is morphologically very similar to the classic phage ViI of
      Salmonella enterica serovar Typhi. Until recently, little was known genetically
      or physiologically about the ViI-like phages, and none targeting E. coli have
      been described in the literature. The genome of CBA120 has been fully sequenced
      and is highly similar to those of both ViI and the Shigella phage AG3. The core
      set of structural and replication-related proteins of CBA120 are homologous to
      those from T-even phages, but generally are more closely related to those from T4
      like phages of Vibrio, Aeromonas and cyanobacteria than those of the
      Enterobacteriaceae. The baseplate and method of adhesion to the host are,
      however, very different from those of either T4 or the cyanophages. None of the
      outer baseplate proteins are conserved. Instead of T4's long and short tail
      fibers, CBA120, like ViI, encodes tail spikes related to those normally seen on
      podoviruses. The 158 kb genome, like that of T4, is circularly permuted and
      terminally redundant, but unlike T4 CBA120 does not substitute hmdCyt for
      cytosine in its DNA. However, in contrast to other coliphages, CBA120 and related
      coliphages we have isolated cannot incorporate 3H-thymidine (3H-dThd) into their
      DNA. Protein sequence comparisons cluster the putative "thymidylate synthase" of
      CBA120, ViI and AG3 much more closely with those of Delftia phage phiW-14,
      Bacillus subtilis phage SPO1, and Pseudomonas phage YuA, all known to produce and
      incorporate hydroxymethyluracil (hmdUra).

PMID- 21899741
TI  - Effect of cinnamon on gastric emptying, arterial stiffness, postprandial lipemia,
      glycemia, and appetite responses to high-fat breakfast.
AB  - BACKGROUND: Cinnamon has been shown to delay gastric emptying of a high
      carbohydrate meal and reduce postprandial glycemia in healthy adults. However, it
      is dietary fat which is implicated in the etiology and is associated with
      obesity, type 2 diabetes and cardiovascular disease. We aimed to determine the
      effect of 3 g cinnamon (Cinnamomum zeylanicum) on GE, postprandial lipemic and
      glycemic responses, oxidative stress, arterial stiffness, as well as appetite
      sensations and subsequent food intake following a high-fat meal. METHODS: A
      single-blind randomized crossover study assessed nine healthy, young subjects. GE
      rate of a high-fat meal supplemented with 3 g cinnamon or placebo was determined
      using the 13C octanoic acid breath test. Breath, blood samples and subjective
      appetite ratings were collected in the fasted and during the 360 min postprandial
      period, followed by an ad libitum buffet meal. Gastric emptying and 1-day fatty
      acid intake relationships were also examined. RESULTS: Cinnamon did not change
      gastric emptying parameters, postprandial triacylglycerol or glucose
      concentrations, oxidative stress, arterial function or appetite (p < 0.05).
      Strong relationships were evident (p < 0.05) between GE Thalf and 1-day
      palmitoleic acid (r = -0.78), eiconsenoic acid (r = -0.84) and total omega-3
      intake (r = -0.72). The ingestion of 3 g cinnamon had no effect on GE, arterial
      stiffness and oxidative stress following a HF meal. CONCLUSIONS: 3 g cinnamon did
      not alter the postprandial response to a high-fat test meal. We find no evidence
      to support the use of 3 g cinnamon supplementation for the prevention or
      treatment of metabolic disease. Dietary fatty acid intake requires consideration
      in future gastrointestinal studies. TRIAL REGISTRATION:  TRIAL REGISTRATION
      NUMBER: at http://www.clinicaltrial.gov: NCT01350284.

PMID- 21899742
TI  - Tumor cell-selective apoptosis induction through targeting of K(V)10.1 via
      bifunctional TRAIL antibody.
AB  - BACKGROUND: The search for strategies to target ion channels for therapeutic
      applications has become of increasing interest. Especially, the potassium channel
      K(V)10.1 (Ether-a-go-go) is attractive as target since this surface protein is
      virtually not detected in normal tissue outside the central nervous system, but
      is expressed in approximately 70% of tumors from different origins. METHODS: We
      designed a single-chain antibody against an extracellular region of K(V)10.1
      (scFv62) and fused it to the human soluble TRAIL. The K(V)10.1-specific scFv62
      antibody -TRAIL fusion protein was expressed in CHO-K1 cells, purified by
      chromatography and tested for biological activity. RESULTS: Prostate cancer
      cells, either positive or negative for K(V)10.1 were treated with the purified
      construct. After sensitization with cytotoxic drugs, scFv62-TRAIL induced
      apoptosis only in K(V)10.1-positive cancer cells, but not in non-tumor cells, nor
      in tumor cells lacking K(V)10.1 expression. In co-cultures with K(V)10.1-positive
      cancer cells the fusion protein also induced apoptosis in bystander K(V)10.1
      negative cancer cells, while normal prostate epithelial cells were not affected
      when present as bystander. CONCLUSIONS: K(V)10.1 represents a novel therapeutic
      target for cancer. We could design a strategy that selectively kills tumor cells
      based on a K(V)10.1-specific antibody.

PMID- 21899743
TI  - Growth of vertically aligned ZnO nanorods using textured ZnO films.
AB  - A hydrothermal method to grow vertical-aligned ZnO nanorod arrays on ZnO films
      obtained by atomic layer deposition (ALD) is presented. The growth of ZnO
      nanorods is studied as function of the crystallographic orientation of the ZnO
      films deposited on silicon (100) substrates. Different thicknesses of ZnO films
      around 40 to 180 nm were obtained and characterized before carrying out the
      growth process by hydrothermal methods. A textured ZnO layer with preferential
      direction in the normal c-axes is formed on substrates by the decomposition of
      diethylzinc to provide nucleation sites for vertical nanorod growth.
      Crystallographic orientation of the ZnO nanorods and ZnO-ALD films was determined
      by X-ray diffraction analysis. Composition, morphologies, length, size, and
      diameter of the nanorods were studied using a scanning electron microscope and
      energy dispersed x-ray spectroscopy analyses. In this work, it is demonstrated
      that crystallinity of the ZnO-ALD films plays an important role in the vertical
      aligned ZnO nanorod growth. The nanorod arrays synthesized in solution had a
      diameter, length, density, and orientation desirable for a potential application
      as photosensitive materials in the manufacture of semiconductor-polymer solar
      cells. PACS: 61.46.Hk, Nanocrystals; 61.46.Km, Structure of nanowires and
      nanorods; 81.07.Gf, Nanowires; 81.15.Gh, Chemical vapor deposition (including
      plasma-enhanced CVD, MOCVD, ALD, etc.).

PMID- 21899745
TI  - Correlation between measures of insulin resistance in fasting and non-fasting
      blood.
AB  - BACKGROUND: Epidemiological investigation of insulin resistance is difficult.
      Standard measures of insulin resistance require invasive investigations, which
      are impractical for large-scale studies. Surrogate measures using fasting blood
      samples have been developed, but even these are difficult to obtain in population
      based studies. Measures of insulin resistance have not been validated in non
      fasting blood samples. Our objective was to assess the correlations between
      fasting and non-fasting measures of insulin resistance/sensitivity. METHODS:
      Fasting and non-fasting measurements of metabolic function were compared in 30
      volunteers (15 male) aged 28 to 48 years. Participants provided a morning blood
      sample after an overnight fast and a second sample approximately 4 hours after
      lunch on the same day. RESULTS: Non-fasting levels of the adipokines leptin,
      adiponectin, and leptin:adiponectin ratios were not significantly different and
      highly correlated with fasting values (r values 0.95, 0.96, and 0.95
      respectively, P values < 0.001). There were moderate correlations between fasting
      and non-fasting estimates of insulin sensitivity using the McAuley (r = 0.60, P =
      0.001) and QUICKI formulae (r = 0.39, P = 0.037). The HOMA-IR estimate of insulin
      resistance was also moderately correlated (r = 0.45, P = 0.016). CONCLUSIONS:
      Semi-fasting measures of leptin, adiponectin, and leptin:adiponectin ratios
      correlate closely with fasting values and are likely to be sufficient for
      population-based research. Other measures of insulin resistance or sensitivity in
      semi-fasted blood samples are moderately correlated with values obtained after an
      overnight fast. These estimates of insulin resistance/sensitivity may also be
      adequate for many epidemiological studies and would avoid the difficulties of
      obtaining fasting blood samples.

PMID- 21899744
TI  - Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell
      lymphoproliferations.
AB  - Epstein-Barr virus (EBV) is a highly successful herpesvirus, colonizing more
      than 90% of the adult human population worldwide, although it is also associated
      with various malignant diseases. Primary infection is usually clinically silent,
      and subsequent establishment of latency in the memory B lymphocyte compartment
      allows persistence of the virus in the infected host for life. EBV is so markedly
      B-lymphotropic when exposed to human lymphocytes in vitro that the association of
      EBV with rare but distinct types of T and NK cell lymphoproliferations was quite
      unexpected. Whilst relatively rare, these EBV-associated T and NK
      lymphoproliferations can be therapeutically challenging and prognosis for the
      majority of patients is dismal. In this review, we summarize the current
      knowledge on the role of EBV in the pathogenesis of these tumours, and the
      implications for treatment.

PMID- 21899746
TI  - Lynch syndrome: barriers to and facilitators of screening and disease management.
AB  - BACKGROUND: Lynch syndrome is a hereditary cancer with confirmed carriers at high
      risk for colorectal (CRC) and extracolonic cancers. The purpose of the current
      study was to develop a greater understanding of the factors influencing decisions
      about disease management post-genetic testing. METHODS: The study used a grounded
      theory approach to data collection and analysis as part of a multiphase project
      examining the psychosocial and behavioral impact of predictive DNA testing for
      Lynch syndrome. Individual and small group interviews were conducted with
      individuals from 10 families with the MSH2 intron 5 splice site mutation or exon
      8 deletion. The data from confirmed carriers (n = 23) were subjected to re
      analysis to identify key barriers to and/or facilitators of screening and disease
      management. RESULTS: Thematic analysis identified personal, health care provider
      and health care system factors as dominant barriers to and/or facilitators of
      managing Lynch syndrome. Person-centered factors reflect risk perceptions and
      decision-making, and enduring screening/disease management. The perceived
      knowledge and clinical management skills of health care providers also influenced
      participation in recommended protocols. The health care system
      barriers/facilitators are defined in terms of continuity of care and coordination
      of services among providers. CONCLUSIONS: Individuals with Lynch syndrome often
      encounter multiple barriers to and facilitators of disease management that go
      beyond the individual to the provider and health care system levels. The current
      organization and implementation of health care services are inadequate. A
      coordinated system of local services capable of providing integrated, efficient
      health care and follow-up, populated by providers with knowledge of hereditary
      cancer, is necessary to maintain optimal health.

PMID- 21899747
TI  - Intrauterine growth retardation--small events, big consequences.
AB  - Intrauterine growth retardation refers to a rate of growth of a fetus that is
      less than normal for the growth potential of a fetus (for that particular
      gestational age). As one of the leading causes of perinatal mortality and
      morbidity, intrauterine growth retardation has immense implications for the short
      term and long term growth of children. It is an important public health concern
      in the developing countries. Health statistics encompassing parameters for
      maternal and child health in the Indian subcontinent have shown improvement in
      the past few years but they are still far from perfect. Maternal health,
      education and empowerment bears a strong influence on perinatal outcomes
      including intrauterine growth retardation and should be the primary focus of any
      stratagem targeted at reducing the incidence of intrauterine growth retardation.
      A concerted liaison of various medical and social disciplines is imperative in
      this regard.

PMID- 21899748
TI  - Comparative performance of precommercial cellulases hydrolyzing pretreated corn
      stover.
AB  - BACKGROUND: Cellulases and related hydrolytic enzymes represent a key cost factor
      for biochemical conversion of cellulosic biomass feedstocks to sugars for
      biofuels and chemicals production. The US Department of Energy (DOE) is cost
      sharing projects to decrease the cost of enzymes for biomass saccharification.
      The performance of benchmark cellulase preparations produced by Danisco, DSM,
      Novozymes and Verenium to convert pretreated corn stover (PCS) cellulose to
      glucose was evaluated under common experimental conditions and is reported here
      in a non-attributed manner. RESULTS: Two hydrolysis modes were examined,
      enzymatic hydrolysis (EH) of PCS whole slurry or washed PCS solids at pH 5 and 50
      degrees C, and simultaneous saccharification and fermentation (SSF) of washed PCS
      solids at pH 5 and 38 degrees C. Enzymes were dosed on a total protein mass
      basis, with protein quantified using both the bicinchoninic acid (BCA) assay and
      the Bradford assay. Substantial differences were observed in absolute cellulose
      to glucose conversion performance levels under the conditions tested. Higher
      cellulose conversion yields were obtained using washed solids compared to whole
      slurry, and estimated enzyme protein dosages required to achieve a particular
      cellulose conversion to glucose yield were extremely dependent on the protein
      assay used. All four enzyme systems achieved glucose yields of 90% of theoretical
      or higher in SSF mode. Glucose yields were reduced in EH mode, with all enzymes
      achieving glucose yields of at least 85% of theoretical on washed PCS solids and
      75% in PCS whole slurry. One of the enzyme systems ('enzyme B') exhibited the
      best overall performance. However in attaining high conversion yields at lower
      total enzyme protein loadings, the relative and rank ordered performance of the
      enzyme systems varied significantly depending upon which hydrolysis mode and
      protein assay were used as the basis for comparison. CONCLUSIONS: This study
      provides extensive information about the performance of four precommercial
      cellulase preparations. Though test conditions were not necessarily optimal for
      some of the enzymes, all were able to effectively saccharify PCS cellulose. Large
      differences in the estimated enzyme dosage requirements depending on the assay
      used to measure protein concentration highlight the need for better consensus
      methods to quantify enzyme protein.

PMID- 21899749
TI  - An extended phylogenetic analysis reveals ancient origin of "non-green"
      phosphoribulokinase genes from two lineages of "green" secondary photosynthetic
      eukaryotes: Euglenophyta and Chlorarachniophyta.
AB  - BACKGROUND: Euglenophyta and Chlorarachniophyta are groups of photosynthetic
      eukaryotes harboring secondary plastids of distinct green algal origins. Although
      previous phylogenetic analyses of genes encoding Calvin cycle enzymes
      demonstrated the presence of genes apparently not derived from green algal
      endosymbionts in the nuclear genomes of Euglena gracilis (Euglenophyta) and
      Bigelowiella natans (Chlorarachniophyta), the origins of these "non-green" genes
      in "green" secondary phototrophs were unclear due to the limited taxon sampling.
      RESULTS: Here, we sequenced five new phosphoribulokinase (PRK) genes (from one
      euglenophyte, two chlorarachniophytes, and two glaucophytes) and performed an
      extended phylogenetic analysis of the genes based on a phylum-wide taxon sampling
      from various photosynthetic eukaryotes. Our phylogenetic analyses demonstrated
      that the PRK sequences form two genera of Euglenophyta formed a robust
      monophyletic group within a large clade including stramenopiles, haptophytes and
      a cryptophyte, and three genera of Chlorarachniophyta were placed within the red
      algal clade. These "non-green" affiliations were supported by the taxon-specific
      insertion/deletion sequences in the PRK alignment, especially between
      euglenophytes and stramenopiles. In addition, phylogenetic analysis of another
      Calvin cycle enzyme, plastid-targeted sedoheptulose-bisphosphatase (SBP), showed
      that the SBP sequences from two genera of Chlorarachniophyta were positioned
      within a red algal clade. CONCLUSIONS: Our results suggest that PRK genes may
      have been transferred from a "stramenopile" ancestor to Euglenophyta and from a
      "red algal" ancestor to Chlorarachniophyta before radiation of extant taxa of
      these two "green" secondary phototrophs. The presence of two of key Calvin cycle
      enzymes, PRK and SBP, of red algal origins in Chlorarachniophyta indicate that
      the contribution of "non-green" algae to the plastid proteome in the "green"
      secondary phototrophs is more significant than ever thought. These "non-green"
      putative plastid-targeted enzymes from Chlorarachniophyta are likely to have
      originated from an ancestral red alga via horizontal gene transfer, or from a
      cryptic red algal endosymbiosis in the common ancestor of the extant
      chlorarachniophytes.

PMID- 21899750
TI  - Infarctions in the vascular territory of the posterior cerebral artery: clinical
      features in 232 patients.
AB  - BACKGROUND: Ischemic stroke caused by infarction in the territory of the
      posterior cerebral artery (PCA) has not been studied as extensively as
      infarctions in other vascular territories. This single centre, retrospective
      clinical study was conducted a) to describe salient characteristics of stroke
      patients with PCA infarction, b) to compare data of these patients with those
      with ischaemic stroke due to middle cerebral artery (MCA) and anterior cerebral
      artery (ACA) infarctions, and c) to identify predictors of PCA stroke. FINDINGS:
      A total of 232 patients with PCA stroke were included in the "Sagrat Cor Hospital
      of Barcelona Stroke Registry" during a period of 19 years (1986-2004). Data from
      stroke patients are entered in the stroke registry following a standardized
      protocol with 161 items regarding demographics, risk factors, clinical features,
      laboratory and neuroimaging data, complications and outcome. The characteristics
      of these 232 patients with PCA stroke were compared with those of the 1355
      patients with MCA infarctions and 51 patients with ACA infarctions included in
      the registry.Infarctions of the PCA accounted for 6.8% of all cases of stroke (n
      = 3808) and 9.6% of cerebral infarctions (n = 2704). Lacunar infarction was the
      most frequent stroke subtype (34.5%) followed by atherothrombotic infarction
      (29.3%) and cardioembolic infarction (21.6%). In-hospital mortality was 3.9% (n =
      9). Forty-five patients (19.4%) were symptom-free at hospital discharge.
      Hemianopia (odds ratio [OR] = 6.43), lacunar stroke subtype (OR = 2.18), symptom
      free at discharge (OR = 1.92), limb weakness (OR = 0.10), speech disorders (OR =
      0.33) and cardioembolism (OR = 0.65) were independent variables of PCA stroke in
      comparison with MCA infarction, whereas sensory deficit (OR = 2.36), limb
      weakness (OR = 0.11) and cardioembolism as stroke mechanism (OR = 0.43) were
      independent variables associated with PCA stroke in comparison with ACA
      infarction. CONCLUSIONS: Lacunar stroke is the main subtype of infarction
      occurring in the PCA territory. Several clinical features are more frequent in
      stroke patients with PCA infarction than in patients with ischaemic stroke due to
      infarction in the MCA and ACA territories. In-hospital mortality in patients with
      PCA territory is low.

PMID- 21899751
TI  - Deep resequencing of the voltage-gated potassium channel subunit KCNE3 gene in
      chronic tinnitus.
AB  - Membrane-stabilizing drugs have long been used for the treatment of chronic
      tinnitus, suggesting an underlying disturbance of sensory excitability due to
      changes in ion conductance. The present study addresses the potassium channel
      subunit gene KCNE3 as a potential candidate for tinnitus susceptibility. 288
      Caucasian outpatients with a diagnosis of chronic tinnitus were systematically
      screened for mutations in the KCNE3 open reading frame and in the adjacent region
      by direct sequencing. Allele frequencies were determined for 11 known variants of
      which two (F66F and R83H) were polymorphic but were not associated with the
      disorder. No novel variants were identified and only three carriers of R83H were
      noted. However, owing to a lack of power, our study can neither rule out effects
      of KCNE3 on the risk for developing chronic tinnitus, nor can it exclude a role
      in predicting the severity of tinnitus. More extensive investigations are
      invited, including tests for possible effects of variation in this ion channel
      protein on the response to treatment.

PMID- 21899752
TI  - Methods to recognize work-related cancer in workplaces, the general population,
      and by experts in the clinic, a Norwegian experience.
AB  - BACKGROUND: In most countries, the numbers of work-related cancer identified are
      much lower than are the estimated total burden of cancer caused by exposure at
      work. Therefore, there is a great need to use all available practical as well as
      epidemiological methods for identification as well as to develop new methods of
      recognizing cases of work-related cancers. METHODS: Primarily based on practical
      experiences from Norway, methods to identify cases of possible work-related
      cancers in the general population and at workplaces as well as methods to
      recognize more specific cases after referral to specialized clinics are reviewed
      in this publication. RESULTS: Countries applying a number of the available
      methods to detect work-related cancer reach a reporting rate of 60 such cases per
      million, while other countries that do not employ such methods hardly identify
      any cases. As most subjects previously exposed to cancer causing agents and
      substances at work are gradually recruited out of work, methods should be
      versatile for identification of cases in the general population, as well as at
      work. CONCLUSIONS: Even in countries using a number of the available methods for
      identification, only a limited fraction of the real number of work-related cancer
      are notified to the labour inspectorate. Clinicians should be familiar with the
      methods and do the best to identify work-related cancer to serve prevention.

PMID- 21899753
TI  - Tailored Implementation For Chronic Diseases (TICD): a project protocol.
AB  - BACKGROUND: The assumption underlying tailoring is that implementation
      interventions are most helpful if these effectively address the most important
      determinants of practice for improvement in the targeted setting. The aim of the
      Tailored Implementation For Chronic Diseases (TICD) project is to develop valid
      and efficient methods of tailoring implementation interventions to determinants
      of practice for knowledge implementation in chronic illness care. METHODS: The
      TICD project has organized the planned empirical research in three work packages
      that follow the three main steps of tailoring: identification of determinants of
      healthcare practice, matching implementation interventions to identified
      determinants of practice, and applying and assessing the tailored implementation
      interventions. These three key steps of tailored implementation will be applied
      to targeted chronic conditions in five different healthcare systems:
      cardiovascular disease in the Netherlands, obesity in England, depression in
      Norway, chronic obstructive pulmonary disease in Poland, and multimorbidity in
      Germany. The design and interpretation of empirical research will be informed by
      systematic reviews of previous research on tailoring implementation
      interventions. DISCUSSION: The TICD project will provide much needed evidence on
      the advantages and disadvantages of different methods of identifying important
      determinants of practice and selecting implementation strategies that take
      account of those. It will also provide five rigorous evaluations of tailored
      implementation interventions for five different chronic conditions.

PMID- 21899754
TI  - A comparison of policy and direct practice stakeholder perceptions of factors
      affecting evidence-based practice implementation using concept mapping.
AB  - BACKGROUND: The goal of this study was to assess potential differences between
      administrators/policymakers and those involved in direct practice regarding
      factors believed to be barriers or facilitating factors to evidence-based
      practice (EBP) implementation in a large public mental health service system in
      the United States. METHODS: Participants included mental health system county
      officials, agency directors, program managers, clinical staff, administrative
      staff, and consumers. As part of concept mapping procedures, brainstorming groups
      were conducted with each target group to identify specific factors believed to be
      barriers or facilitating factors to EBP implementation in a large public mental
      health system. Statements were sorted by similarity and rated by each participant
      in regard to their perceived importance and changeability. Multidimensional
      scaling, cluster analysis, descriptive statistics and t-tests were used to
      analyze the data. RESULTS: A total of 105 statements were distilled into 14
      clusters using concept-mapping procedures. Perceptions of importance of factors
      affecting EBP implementation varied between the two groups, with those involved
      in direct practice assigning significantly higher ratings to the importance of
      Clinical Perceptions and the impact of EBP implementation on clinical practice.
      Consistent with previous studies, financial concerns (costs, funding) were rated
      among the most important and least likely to change by both groups. CONCLUSIONS:
      EBP implementation is a complex process, and different stakeholders may hold
      different opinions regarding the relative importance of the impact of EBP
      implementation. Implementation efforts must include input from stakeholders at
      multiple levels to bring divergent and convergent perspectives to light.

PMID- 21899755
TI  - Dysembryoplastic neuroepithelial tumor and probable sudden unexplained death in
      epilepsy: a case report.
AB  - INTRODUCTION: This is the first report of the case of a patient with a natural
      history of dysembryoplastic neuroepithelial tumor associated with probable sudden
      unexplained death in epilepsy. These tumors are benign, arising within the
      supratentorial cortex. Over 100 cases have been reported in the literature since
      the first description by Daumas-Duport in 1988. CASE PRESENTATION: A 24- year-old
      Caucasian woman had a long period of intractable complex partial seizures,
      sometimes with tonic-clonic generalization and neuropsychological abnormalities.
      Magnetic resonance imaging showed a cortico-subcortical parietal tumor with all
      the characteristics of these types of tumors. After 14 years of evolution, our
      patient died suddenly during sleep. CONCLUSION: To the best of our knowledge,
      this is the first case of probable sudden unexplained death in symptomatic
      epilepsy due to dysembryoplastic neuroepithelial tumor with natural history.
      Early and complete excision, with functional studies before and during the
      surgery, leads to better control of seizures, avoiding neuropsychological changes
      and the risk of death. Patients with refractory epilepsy should be evaluated for
      any sleep disorders and should have complete cardiology assessments including
      electrocardiographic evaluation of cardiac rhythm disturbances.

PMID- 21899756
TI  - Giant right coronary artery aneurysm presenting with non-ST elevation myocardial
      infarction and severe mitral regurgitation: a case report.
AB  - INTRODUCTION: Coronary artery aneurysms are seen in 1.5-5% of patients presenting
      for coronary angiography, but giant aneurysms, defined as being greater than 2 cm
      in diameter, are rare. Given the paucity of cases and limited experience in
      diagnosis and management of the disease, each case is a learning tool in itself.
      CASE PRESENTATION: We report the rare case of a 78-year-old Caucasian man who
      presented to a peripheral emergency department with chest pain and was
      subsequently found to have a giant right coronary artery aneurysm. Following
      initial investigation and treatment he was referred to our hospital for
      definitive management. CONCLUSION: The case described illustrates one of the
      varied presentations and subsequent management of an ill-defined and
      heterogeneous disease process. Given the limited experience with giant aneurysms
      in the coronary circulation, this case provides valuable insight into the
      clinical presentation of the disease and gives an example of the management of
      the most recent such case at our hospital.

PMID- 21899757
TI  - Pigmented villonodular synovitis of the hip in systemic lupus erythematosus: a
      case report.
AB  - INTRODUCTION: Pigmented villonodular synovitis is a rare disease of unknown
      etiology mostly affecting the knee and foot. Until now an association with
      autoimmune diseases has not been reported. CASE PRESENTATION: The diagnosis of
      systemic lupus erythematosus was made in a 15-year-old Caucasian girl based on
      otherwise unexplained fatigue, arthralgia, tenosynovitis, leukopenia, low
      platelets and the presence of antinuclear and deoxyribonucleic antibodies. At the
      age of 20 a renal biopsy revealed lupus nephritis class IV and she went into
      complete remission with mycophenolate mofetil and steroids. She was kept on
      mycophenolate mofetil for maintenance therapy. At the age of 24 she experienced a
      flare-up of lupus nephritis with nephrotic syndrome and new onset of pain in her
      right hip. Magnetic resonance imaging, arthroscopy and subtotal synovectomy
      identified pigmented villonodular synovitis as the underlying diagnosis. Although
      her systemic lupus erythematosus went into remission with another course of
      steroids and higher doses of mycophenolate mofetil, the pigmented villonodular
      synovitis persisted and she had to undergo open synovectomy to control her
      symptoms. CONCLUSION: Systemic lupus erythematosus is associated with many
      different musculoskeletal manifestations including synovitis and arthritis.
      Pigmented villonodular synovitis has not previously been reported in association
      with systemic lupus erythematosus, but as its etiology is still unknown, the
      present case raises the question about a causal relationship between systemic
      lupus erythematosus and pigmented villonodular synovitis.

PMID- 21899758
TI  - Acute abdomen due to spontaneous splenic rupture as the first presentation of
      lung malignancy: a case report.
AB  - INTRODUCTION: Spontaneous splenic rupture is well recognized in the context of
      hematological malignancies (lymphoproliferative and myeloproliferative
      disorders); a few case reports have also linked solid tumors, such as pancreatic
      and liver cancer, with the occurrence of spontaneous splenic rupture. This is the
      first case report of lung cancer as a likely cause of spontaneous splenic
      rupture. CASE PRESENTATION: A 61-year-old Caucasian woman presented to our
      hospital with non-specific symptoms. She developed an 'acute' abdomen and went
      into a state of shock within twelve hours of her presentation. She was diagnosed
      with spontaneous splenic rupture with radiology and following a laparotomy. She
      made an uneventful recovery postoperatively and was simultaneously found to have
      a bronchial adenocarcinoma. CONCLUSION: Spontaneous splenic rupture is a
      potentially fatal but often unrecognized cause of acute abdomen. It should be
      routinely considered in the differential diagnosis of acute ('surgical') abdomen
      and when present it should be promptly dealt with, most commonly with a
      laparotomy. Once the diagnosis is confirmed there should be an aggressive drive
      to identify an underlying etiology; malignancy is the commonest culprit. Solid
      tumors should be considered as underlying causes despite being less common than
      hematological neoplasms. This case report demonstrates lung malignancy as an
      underlying precipitating cause of spontaneous splenic rupture.

PMID- 21899759
TI  - The putative Notch ligand HyJagged is a transmembrane protein present in all cell
      types of adult Hydra and upregulated at the boundary between bud and parent.
AB  - BACKGROUND: The Notch signalling pathway is conserved in pre-bilaterian animals.
      In the Cnidarian Hydra it is involved in interstitial stem cell differentiation
      and in boundary formation during budding. Experimental evidence suggests that in
      Hydra Notch is activated by presenilin through proteolytic cleavage at the S3
      site as in all animals. However, the endogenous ligand for HvNotch has not been
      described yet. RESULTS: We have cloned a cDNA from Hydra, which encodes a bona
      fide Notch ligand with a conserved domain structure similar to that of Jagged
      like Notch ligands from other animals. Hyjagged mRNA is undetectable in adult
      Hydra by in situ hybridisation but is strongly upregulated and easily visible at
      the border between bud and parent shortly before bud detachment. In contrast,
      HyJagged protein is found in all cell types of an adult hydra, where it localises
      to membranes and endosomes. Co-localisation experiments showed that it is present
      in the same cells as HvNotch, however not always in the same membrane structures.
      CONCLUSIONS: The putative Notch ligand HyJagged is conserved in Cnidarians.
      Together with HvNotch it may be involved in the formation of the parent-bud
      boundary in Hydra. Moreover, protein distribution of both, HvNotch receptor and
      HyJagged indicate a more widespread function for these two transmembrane proteins
      in the adult hydra, which may be regulated by additional factors, possibly
      involving endocytic pathways.

PMID- 21899760
TI  - Comprehensive SNP array study of frequently used neuroblastoma cell lines; copy
      neutral loss of heterozygosity is common in the cell lines but uncommon in
      primary tumors.
AB  - BACKGROUND: Copy neutral loss of heterozygosity (CN-LOH) refers to a special case
      of LOH occurring without any resulting loss in copy number. These alterations is
      sometimes seen in tumors as a way to inactivate a tumor suppressor gene and have
      been found to be important in several types of cancer. RESULTS: We have used high
      density single nucleotide polymorphism arrays in order to investigate the
      frequency and distribution of CN-LOH and other allelic imbalances in
      neuroblastoma (NB) tumors and cell lines. Our results show that the frequency of
      these near-CN-LOH events is significantly higher in the cell lines compared to
      the primary tumors and that the types of CN-LOH differ between the groups. We
      also show that the low-risk neuroblastomas that are generally considered to have
      a "triploid karyotype" often present with a complex numerical karyotype (no
      segmental changes) with 2-5 copies of each chromosome. Furthermore a comparison
      has been made between the three related cell lines SK-N-SH, SH-EP and SH-SY5Y
      with respect to overall genetic aberrations, and several aberrations unique to
      each of the cell lines has been found. CONCLUSIONS: We have shown that the NB
      tumors analyzed contain several interesting allelic imbalances that would either
      go unnoticed or be misinterpreted using other genome-wide techniques. These
      findings indicate that the genetics underlying NB might be even more complex than
      previously known and that SNP arrays are important analysis tools. We have also
      showed that these near-CN-LOH events are more frequently seen in NB cell lines
      compared to NB tumors and that a set of highly related cell lines have continued
      to evolve secondary to the subcloning event. Taken together our analysis
      highlights that cell lines in many cases differ substantially from the primary
      tumors they are thought to represent, and that caution should be taken when
      drawing conclusions from cell line-based studies.

PMID- 21899761
TI  - WebMGA: a customizable web server for fast metagenomic sequence analysis.
AB  - BACKGROUND: The new field of metagenomics studies microorganism communities by
      culture-independent sequencing. With the advances in next-generation sequencing
      techniques, researchers are facing tremendous challenges in metagenomic data
      analysis due to huge quantity and high complexity of sequence data. Analyzing
      large datasets is extremely time-consuming; also metagenomic annotation involves
      a wide range of computational tools, which are difficult to be installed and
      maintained by common users. The tools provided by the few available web servers
      are also limited and have various constraints such as login requirement, long
      waiting time, inability to configure pipelines etc. RESULTS: We developed WebMGA,
      a customizable web server for fast metagenomic analysis. WebMGA includes over 20
      commonly used tools such as ORF calling, sequence clustering, quality control of
      raw reads, removal of sequencing artifacts and contaminations, taxonomic
      analysis, functional annotation etc. WebMGA provides users with rapid metagenomic
      data analysis using fast and effective tools, which have been implemented to run
      in parallel on our local computer cluster. Users can access WebMGA through web
      browsers or programming scripts to perform individual analysis or to configure
      and run customized pipelines. WebMGA is freely available at http://weizhongli
      lab.org/metagenomic-analysis. CONCLUSIONS: WebMGA offers to researchers many fast
      and unique tools and great flexibility for complex metagenomic data analysis.

PMID- 21899762
TI  - A method for zooming of nonlinear models of biochemical systems.
AB  - BACKGROUND: Models of biochemical systems are typically complex, which may
      complicate the discovery of cardinal biochemical principles. It is therefore
      important to single out the parts of a model that are essential for the function
      of the system, so that the remaining non-essential parts can be eliminated.
      However, each component of a mechanistic model has a clear biochemical
      interpretation, and it is desirable to conserve as much of this interpretability
      as possible in the reduction process. Furthermore, it is of great advantage if we
      can translate predictions from the reduced model to the original model. RESULTS:
      In this paper we present a novel method for model reduction that generates
      reduced models with a clear biochemical interpretation. Unlike conventional
      methods for model reduction our method enables the mapping of predictions by the
      reduced model to the corresponding detailed predictions by the original model.
      The method is based on proper lumping of state variables interacting on short
      time scales and on the computation of fraction parameters, which serve as the
      link between the reduced model and the original model. We illustrate the
      advantages of the proposed method by applying it to two biochemical models. The
      first model is of modest size and is commonly occurring as a part of larger
      models. The second model describes glucose transport across the cell membrane in
      baker's yeast. Both models can be significantly reduced with the proposed method,
      at the same time as the interpretability is conserved. CONCLUSIONS: We introduce
      a novel method for reduction of biochemical models that is compatible with the
      concept of zooming. Zooming allows the modeler to work on different levels of
      model granularity, and enables a direct interpretation of how modifications to
      the model on one level affect the model on other levels in the hierarchy. The
      method extends the applicability of the method that was previously developed for
      zooming of linear biochemical models to nonlinear models.

PMID- 21899763
TI  - How often is a work-up for Legionella pursued in patients with pneumonia? a
      retrospective study.
AB  - BACKGROUND: It is unclear how often patients with pneumonia are assessed for
      Legionella in endemic areas. Additionally, the sensitivity of the IDSA/ATS
      criteria for recommended Legionella testing is undefined. METHODS: We performed a
      single-center, retrospective study of patients diagnosed with Legionella
      pneumonia at our hospital to determine: 1) how often Legionella diagnostic
      testing is obtained on patients with pneumonia at the time of hospitalization or
      when pneumonia developed during hospitalization; and 2) how often patient's with
      Legionella pneumonia met at least one of the five criteria in the IDSA/ATS
      guidelines recommending a work-up for Legionella. Patients with Legionella
      pneumonia were identified using an infection control software program. Medical
      records of these patients were then reviewed. RESULTS: Thirty-five percent of
      patients with a discharge diagnosis of pneumonia had Legionella urine antigen
      testing and/or a Legionella culture performed. Forty-four percent of patients who
      had a bronchoscopic specimen sent for microbiologic testing had a Legionella
      culture performed on the bronchoscopic specimen and/or Legionella urine antigen
      testing. Of 37 adult patients with Legionella pneumonia, 22 (59%) met the IDSA
      ATS criteria recommending Legionella testing. CONCLUSION: Following current
      recommendations for Legionella testing missed 41% of Legionella cases in adults
      in our single-center study. A work-up for Legionella (i.e., urine antigen test
      and/or culture) was performed in less than half of patients who have a
      bronchoscopic specimen sent for microbiologic testing.

PMID- 21899764
TI  - Peer-based behavioral health program for drug users in China: a pilot study.
AB  - BACKGROUND: Many injection drug users (IDUs) in China have high risk sexual
      behaviors that contribute to the spread of HIV infection. Although many IDUs in
      China move through drug rehabilitation centers, this opportunity for sexual
      health education has largely been overlooked. METHODS: A convenience sample of
      667 drug users from two rehabilitation centers in South China was recruited in
      the study. Two hundred and forty seven drug users from a single Guangdong
      Province rehabilitation center received the peer-based education intervention,
      while 420 drug users from another rehabilitation center received routine HIV/STI
      education and was used as the control. One hundred and eighty nine (22.1%)
      individuals refused to participate in the study. HIV/STI behavioral and knowledge
      domains were assessed at 3 months in rehabilitation centers after the
      intervention (first follow-up) and at 2-23 months in the community after release
      (second follow-up). RESULTS: Drug users who completed the intervention reported
      more frequent condom use with casual sex partners (60.0% vs. 12.5% condom use
      every time, p = 0.011) and less frequent injection (56.7% vs. 26.4% no injection
      per day, p = 0.008) at the second follow-up compared to those in the routine
      education group. Loss to follow up was substantial in both control and
      intervention groups, and was associated with living far from the detention center
      and having poor HIV knowledge at baseline. CONCLUSIONS: This study shows that
      rehabilitation centers may be a useful location for providing behavioral HIV/STI
      prevention services and referral of individuals to community-based programs upon
      release. More research is needed on behalf of detained drug users in China who
      have complex social, medical, and legal needs.

PMID- 21899765
TI  - Pertussis resurgence in Toronto, Canada: a population-based study including test
      incidence feedback modeling.
AB  - BACKGROUND: Pertussis continues to challenge medical professionals; recently
      described increases in incidence may be due to age-cohort effects, vaccine
      effectiveness, or changes in testing patterns. Toronto, Canada has recently
      experienced increases in pertussis incidence, and provides an ideal jurisdiction
      for evaluating pertussis epidemiology due to centralized testing. We evaluated
      pertussis trends in Toronto using all available specimen data, which allowed us
      to control for changing testing patterns and practices. METHODS: Data included
      all pertussis culture and PCR test records for Greater Toronto from 1993 to 2007.
      We estimated incidence trends using Poisson regression models; complex
      relationships between disease incidence and test submission were explored with
      vector autoregressive models. RESULTS: From 1993 to 2007, 26988 specimens were
      submitted for testing; 2545 (9.4%) were positive. Pertussis incidence was 2 per
      100,000 from 1993 to 2004 and increased to 10 per 100,000 from 2005-2007, with a
      concomitant 6-fold surge in test specimen submissions after the introduction of a
      new, more sensitive PCR assay. The relative change in incidence was less marked
      after adjustment for testing volumes. Bidirectional feedbacks between test
      positivity and test submissions were identified. CONCLUSIONS: Toronto's recent
      surge in pertussis reflects a true increase in local disease activity; the
      apparent size of the outbreak has likely been magnified by increasing use of
      pertussis testing by clinicians, and by improved test sensitivity since 2005.
      These findings may be applicable to changes in pertussis epidemiology that have
      been noted elsewhere in North America.

PMID- 21899766
TI  - Impact of information letters on the reporting rate of adverse drug reactions and
      the quality of the reports: a randomized controlled study.
AB  - BACKGROUND: Spontaneous reporting of adverse drug reactions (ADRs) is an
      important method for pharmacovigilance, but under-reporting and poor quality of
      reports are major limitations. The aim of this study was to evaluate if repeated
      one-page ADR information letters affect (i) the reporting rate of ADRs and (ii)
      the quality of the ADR reports. METHODS: All 151 primary healthcare units in the
      Region Vastra Gotaland, Sweden, were randomly allocated (1:1) to an intervention
      (n = 77) or a control group (n = 74). The intervention consisted of one-page ADR
      information letters administered at three occasions during 2008 to all physicians
      and nurses in the intervention units. The number of ADR reports received from the
      151 units was registered, as was the quality of the reports, which was defined as
      high if the ADR was to be reported according to Swedish regulations, that is, if
      the ADR was (i) serious, (ii) unexpected, and/or (iii) related to the use of new
      drugs and not labelled as common in the Summary of Product Characteristics. A
      questionnaire was administered to evaluate if the ADR information letter had
      reached the intended recipient. RESULTS: Before the intervention, no significant
      differences in reporting rate or number of high quality reports could be detected
      between the randomization groups. In 2008, 79 reports were sent from 37
      intervention units and 52 reports from 30 control units (mean number of reports
      per unit +/- standard deviation: 1.0 +/- 2.5 vs. 0.7 +/- 1.2, P = 0.34). The
      number of high quality reports was higher in intervention units than in control
      units (37 vs. 15 reports, 0.5 +/- 0.9 vs. 0.2 +/- 0.6, P = 0.048). According to
      the returned questionnaires (n = 1,292, response rate 57%), more persons in the
      intervention than in the control group had received (29% vs. 19%, P < 0.0001) and
      read (31% vs. 26%, P < 0.0001) an ADR information letter. CONCLUSIONS: This study
      suggests that repeated ADR information letters to physicians and nurses do not
      increase the ADR reporting rate, but may increase the number of high quality
      reports.

PMID- 21899767
TI  - Evaluating risk factor assumptions: a simulation-based approach.
AB  - BACKGROUND: Microsimulation models are an important tool for estimating the
      comparative effectiveness of interventions through prediction of individual-level
      disease outcomes for a hypothetical population. To estimate the effectiveness of
      interventions targeted toward high risk groups, the mechanism by which risk
      factors influence the natural history of disease must be specified. We propose a
      method for evaluating these risk factor assumptions as part of model-building.
      METHODS: We used simulation studies to examine the impact of risk factor
      assumptions on the relative rate (RR) of colorectal cancer (CRC) incidence and
      mortality for a cohort with a risk factor compared to a cohort without the risk
      factor using an extension of the CRC-SPIN model for colorectal cancer. We also
      compared the impact of changing age at initiation of screening colonoscopy for
      different risk mechanisms. RESULTS: Across CRC-specific risk factor mechanisms,
      the RR of CRC incidence and mortality decreased (towards one) with increasing
      age. The rate of change in RRs across age groups depended on both the risk factor
      mechanism and the strength of the risk factor effect. Increased non-CRC mortality
      attenuated the effect of CRC-specific risk factors on the RR of CRC when both
      were present. For each risk factor mechanism, earlier initiation of screening
      resulted in more life years gained, though the magnitude of life years gained
      varied across risk mechanisms. CONCLUSIONS: Simulation studies can provide
      insight into both the effect of risk factor assumptions on model predictions and
      the type of data needed to calibrate risk factor models.

PMID- 21899768
TI  - Prioritizing orphan proteins for further study using phylogenomics and gene
      expression profiles in Streptomyces coelicolor.
AB  - BACKGROUND: Streptomyces coelicolor, a model organism of antibiotic producing
      bacteria, has one of the largest genomes of the bacterial kingdom, including 7825
      predicted protein coding genes. A large number of these genes, nearly 34%, are
      functionally orphan (hypothetical proteins with unknown function). However, in
      gene expression time course data, many of these functionally orphan genes show
      interesting expression patterns. RESULTS: In this paper, we analyzed all
      functionally orphan genes of Streptomyces coelicolor and identified a list of
      "high priority" orphans by combining gene expression analysis and additional
      phylogenetic information (i.e. the level of evolutionary conservation of each
      protein). CONCLUSIONS: The prioritized orphan genes are promising candidates to
      be examined experimentally in the lab for further characterization of their
      function.

PMID- 21899769
TI  - High prevalence of methicillin resistant Staphylococcus aureus in the surgical
      units of Mulago hospital in Kampala, Uganda.
AB  - BACKGROUND: There is limited data on Methicillin resistant Staphylococcus aureus
      (MRSA) in Uganda where, as in most low income countries, the routine use of
      chromogenic agar for MRSA detection is not affordable. We aimed to determine MRSA
      prevalence among patients, healthcare workers (HCW) and the environment in the
      burns units at Mulago hospital, and compare the performance of CHROMagar with
      oxacillin for detection of MRSA. RESULTS: One hundred samples (from 25 patients;
      36 HCW; and 39 from the environment, one sample per person/item) were cultured
      for the isolation of Staphylococcus aureus. Forty one S. aureus isolates were
      recovered from 13 patients, 13 HCW and 15 from the environment, all of which were
      oxacillin resistant and mecA/femA/nuc-positive. MRSA prevalence was 46% (41/89)
      among patients, HCW and the environment, and 100% (41/41) among the isolates. For
      CHROMagar, MRSA prevalence was 29% (26/89) among patients, HCW and the
      environment, and 63% (26/41) among the isolates. There was high prevalence of
      multidrug resistant isolates, which concomitantly possessed virulence and
      antimicrobial resistance determinants, notably biofilms, hemolysins, toxin and
      ica genes. One isolate positive for all determinants possessed the bhp homologue
      which encodes the biofilm associated protein (BAP), a rare finding in human
      isolates. SCCmec type I was the most common at 54% prevalence (22/41), followed
      by SCCmec type V (15%, 6/41) and SCCmec type IV (7%, 3/41). SCCmec types II and
      III were not detected and 10 isolates (24%) were non-typeable. CONCLUSIONS: Hyper
      virulent methicillin resistant Staphylococcus aureus is prevalent in the burns
      unit of Mulago hospital.

PMID- 21899770
TI  - Genetic variation in the tau protein phosphatase-2A pathway is not associated
      with Alzheimer's disease risk.
AB  - BACKGROUND: Tau abnormal hyperphosphorylation and the formation of
      neurofibrillary tangles in AD brain is the result of upregulation of tau kinases
      and downregulation of tau phosphatases. METHODS: In a group of 729 Spanish late
      onset Alzheimer's disease (AD) patients and 670 healthy controls, we examined
      variations into a set of candidate genes (PPP2CA, PPP2R2A, ANP32A, LCMT1, PPME1
      and PIN1) in the tau protein phosphatase-2A (PP2A) pathway, to address hypotheses
      of genetic variation that might influence AD risk. RESULTS: There were no
      differences in the genotypic, allelic or haplotypic distributions between cases
      and controls in the overall analysis or after stratification by age, gender or
      APOE epsilon4 allele. CONCLUSION: Our negative findings in the Spanish population
      argue against the hypothesis that genetic variation in the tau protein
      phosphatase-2A (PP2A) pathway is causally related to AD risk.

PMID- 21899771
TI  - Demographic differences between health care workers who did or did not respond to
      a safety and organizational culture survey.
AB  - BACKGROUND: Areas for institutional improvement to enhance patient safety are
      commonly identified by surveying health care workers' (HCWs) attitudes, values,
      beliefs, perceptions and assumptions regarding institutional practices. An ideal
      response rate of 100% is rarely achieved in such surveys, and non-response bias
      can occur when non-respondents differ from respondents on a dimension likely to
      influence survey conclusions. The conditions for non-response bias to occur can
      be detected by comparing demographic characteristics of respondents and non
      respondents and relating any differences to findings in the literature of
      differences in the construct of interest as a function of these demographic
      characteristics. The current study takes this approach. FINDINGS: All 5,609 HCWs
      at a university medical center were invited to participate in a survey measuring
      safety and organizational culture (response rate = 53.40%). Respondents indicated
      their professional group, gender, age group, years of working in the hospital and
      executive function. Because all HCWs were invited, the demographic composition of
      the group who did not respond was known. Differences in the demographic
      composition of respondents and non-respondents were compared using separate
      Pearson's chi-square tests for each demographic characteristic.Nurses and
      clinical workers were generally more likely to respond than were physicians,
      laboratory workers and non-medical workers. Male HCWs were less likely to respond
      than were females, HCWs aged younger than 45 years old had a lower response rate
      than did HCWs aged 45 to 54 years old, HCWs who had worked in the hospital for
      less than 5 years were less likely to respond than were those who had worked in
      the hospital for 5 years or more and HCWs without an executive function were less
      likely to respond than were executives. CONCLUSIONS: Demographic characteristics
      can be linked to response rates and need to be considered in conducting surveys
      among HCWs. The possibility of non-response bias can be reduced by conducting
      analyses separately as a function of relevant demographic characteristics,
      sampling a higher percentage of groups that are known to be less likely to
      respond, or weighting responses with the reciprocal of the response rate for the
      respective demographic group.

PMID- 21899772
TI  - PCR could be a method of choice for identification of both pulmonary and extra
      pulmonary tuberculosis.
AB  - BACKGROUND: Nucleic acid amplification assays including PCR have revolutionized
      the detection of Mycobacterium tuberculosis (MTB). Tuberculosis spread to almost
      every organ of the body and is characterized on the basis of localization of
      infection. Therefore, different types of body fluids and tissues can be used for
      the detection of MTB.From 2004 to 2010 total 766 different types of smear
      negative samples from patients, clinically suspected for tuberculosis were
      received and investigated at Division of Molecular Diagnostics, University of the
      Punjab Lahore for the diagnosis of tuberculosis. Mycobacterial DNA was extracted
      followed by PCR amplification. FINDINGS: A total of 356 (46.5%) samples were
      found positive by PCR for MTB. These included; serum (4.8%), blood (36.3%), urine
      (46.6%), cerebro spinal fluid (CSF) (42.1%), ascetic fluid (67.6%), pleural fluid
      (52%), pericardial fluid (30%), pus (38.6%), bone marrow (60%), sputum (38.8%)
      and bronchoalveolar lavage (BAL) (70%). Over all there was no significant
      difference in males and females neither in different age groups for the
      identification of MTB. CONCLUSION: We conclude that PCR is a useful and sensitive
      tool for the early diagnosis of MTB in variety of clinical samples.

PMID- 21899773
TI  - The value of age and medical history for predicting colorectal cancer and
      adenomas in people referred for colonoscopy.
AB  - BACKGROUND: Colonoscopy is an invasive and costly procedure with a risk of
      serious complications. It would therefore be useful to prioritise colonoscopies
      by identifying people at higher risk of either cancer or premalignant adenomas.
      The aim of this study is to assess a model that identifies people with colorectal
      cancer, advanced, large and small adenomas. METHODS: Patients seen by
      gastroenterologists and colorectal surgeons between April 2004 and December 2006
      completed a validated, structured self-administered questionnaire prior to
      colonoscopy. Information was collected on symptoms, demographics and medical
      history. Multinomial logistic regression was used to simultaneously assess
      factors associated with findings on colonoscopy of cancer, advanced adenomas and
      adenomas sized 6 -9 mm, and <= 5 mm. The area under the curve of ROC curve was
      used to assess the incremental gain of adding demographic variables, medical
      history and symptoms (in that order) to a base model that included only age.
      RESULTS: Sociodemographic variables, medical history and symptoms (from 8,204
      patients) jointly provide good discrimination between colorectal cancer and no
      abnormality (AUC 0.83), but discriminate less well between adenomas and no
      abnormality (AUC advanced adenoma 0.70; other adenomas 0.67). Age is the dominant
      risk factor for cancer and adenomas of all sizes. Having a colonoscopy within the
      last 10 years confers protection for cancers and advanced adenomas. CONCLUSIONS:
      Our models provide guidance about which factors can assist in identifying people
      at higher risk of disease using easily elicited information. This would allow
      colonoscopy to be prioritised for those for whom it would be of most benefit.

PMID- 21899774
TI  - Agile parallel bioinformatics workflow management using Pwrake.
AB  - BACKGROUND: In bioinformatics projects, scientific workflow systems are widely
      used to manage computational procedures. Full-featured workflow systems have been
      proposed to fulfil the demand for workflow management. However, such systems tend
      to be over-weighted for actual bioinformatics practices. We realize that quick
      deployment of cutting-edge software implementing advanced algorithms and data
      formats, and continuous adaptation to changes in computational resources and the
      environment are often prioritized in scientific workflow management. These
      features have a greater affinity with the agile software development method
      through iterative development phases after trial and error.Here, we show the
      application of a scientific workflow system Pwrake to bioinformatics workflows.
      Pwrake is a parallel workflow extension of Ruby's standard build tool Rake, the
      flexibility of which has been demonstrated in the astronomy domain. Therefore, we
      hypothesize that Pwrake also has advantages in actual bioinformatics workflows.
      FINDINGS: We implemented the Pwrake workflows to process next generation
      sequencing data using the Genomic Analysis Toolkit (GATK) and Dindel. GATK and
      Dindel workflows are typical examples of sequential and parallel workflows,
      respectively. We found that in practice, actual scientific workflow development
      iterates over two phases, the workflow definition phase and the parameter
      adjustment phase. We introduced separate workflow definitions to help focus on
      each of the two developmental phases, as well as helper methods to simplify the
      descriptions. This approach increased iterative development efficiency. Moreover,
      we implemented combined workflows to demonstrate modularity of the GATK and
      Dindel workflows. CONCLUSIONS: Pwrake enables agile management of scientific
      workflows in the bioinformatics domain. The internal domain specific language
      design built on Ruby gives the flexibility of rakefiles for writing scientific
      workflows. Furthermore, readability and maintainability of rakefiles may
      facilitate sharing workflows among the scientific community. Workflows for GATK
      and Dindel are available at http://github.com/misshie/Workflows.

PMID- 21899775
TI  - A life course approach to injury prevention: a "lens and telescope" conceptual
      model.
AB  - BACKGROUND: Although life course epidemiology is increasingly employed to
      conceptualize the determinants of health, the implications of this approach for
      strategies to reduce the burden of injuries have received little recognition to
      date. METHODS: The authors reviewed core injury concepts and the principles of
      the life course approach. Based on this understanding, a conceptual model was
      developed, to provide a holistic view of the mechanisms that underlie the
      accumulation of injury risk and their consequences over the life course. RESULTS:
      A "lens and telescope" model is proposed that particularly draws on (a) the
      extended temporal dimension inherent in the life course approach, with links
      between exposures and outcomes that span many years, or even generations, and (b)
      an ecological perspective, according to which the contexts in which individuals
      live are critical, as are changes in those contexts over time. CONCLUSIONS: By
      explicitly examining longer-term, intergenerational and ecological perspectives,
      life course concepts can inform and strengthen traditional approaches to injury
      prevention and control that have a strong focus on proximal factors. The model
      proposed also serves as a tool to identify intervention strategies that have co
      benefits for other areas of health.

PMID- 21899777
TI  - Conservative treatment of fractures of the clavicle.
AB  - BACKGROUND: In the treatment of clavicle fractures, the choice of procedure
      depends on the possibility of restoring the anatomical functional integrity of
      the shoulder. METHODS: We examined 71 patients (51 males and 20 females, mean age
      38.9 years) who were affected by clavicle fracture sequelae. Demographic and
      clinical data and the site of the lesion were recorded for each partecipant. The
      dissatisfaction of the patient was determined by the presence of 1 or more
      affirmative answers on the Simple Shoulder Test. The Constant Shoulder Score was
      also included in the functional and clinical exams. We measured the length of the
      healthy clavicle and the previously fractured clavicle, and we expressed the
      difference in length in mm and in percentage shortening. We then examined the
      correlations between the shortening of the bone and the clinical and functional
      outcomes of the patients. RESULTS: Sixty patients had a lesion of the diaphysis,
      8 patients had a lesion of the lateral third of the clavicle, and 3 patients had
      a lesion of the medial third of the clavicle. The mean Constant Shoulder Score
      was 77.9, and 51 of the 71 patients were satisfied with their treatment.
      Radiography showed a mean clavicle shortening of 10 mm (mean percentage 6.5%). In
      the 20 dissatisfied patients, the mean clavicle shortening was 15.2 mm (9.7%). In
      these patients, we found a highly significant association between dissatisfaction
      with treatment and the amount of bone shortening, (p < 0.0001), as well as with a
      diaphyseal location (p < 0.05) and with the female sex (p = 0.004). No other
      variable related to the patient, the type of treatment or the fracture
      characteristics correlated with the treatment outcome. CONCLUSIONS: In the
      literature, measurements of the shortening of the bone segment following a
      fracture range between 15 and 23 mm, and marked shortening is correlated with the
      failure of conservative treatment. However, these data need to be reinterpreted
      in light of the physiological variability of the clavicle length, which ranges
      from 140 to 158 mm in the healthy population. Shortening of the bone by more than
      9.7% should be the cut-off for predicting failure of conservative treatment.

PMID- 21899776
TI  - Identification of ionotrophic purinergic receptors in Huh-7 cells and their
      response towards structural proteins of HCV genotype 3a.
AB  - Hepatitis C virus (HCV) is a major health problem in developing countries
      including Pakistan. Chronic HCV infection results in progressive liver disease
      including fibrosis, cirrhosis, insulin resistance and eventually hepatocellular
      carcinoma (HCC). Ionotrophic purinergic (P2X) receptors are identified to involve
      in a spectrum of physiological and pathophysiological processes. However, the
      role of P2X receptors in HCV liver associated diseases still remains to be
      investigated. The current study was designed to identify the presence of P2X
      receptors in human liver cells. Furthermore, it investigates the response of P2X
      receptors towards HCV structural proteins (E1E2). To determine that how many
      isoforms of P2X receptors are expressed in human liver cells, human hepatoma cell
      line (Huh-7) was used. Transcripts (mRNA) of five different isoforms of P2X
      receptors were identified in Huh-7 cells. To examine the gene expression of
      identified isoforms of P2X receptors in presence of HCV structural proteins E1E2,
      Huh-7/E1E2 cell line (stably expressing HCV structural proteins E1E2) was used.
      The results showed significant increase (6.2 fold) in gene expression of P2X4
      receptors in Huh-7/E1E2 cells as compared to control Huh-7 cells. The findings of
      present study confirmed the presence of transcripts of five different isoforms of
      P2X receptors in human liver cells and suggest that P2X4 receptors could be
      represented an important component of the purinergic signaling complex in HCV
      induced liver pathogenesis.

PMID- 21899778
TI  - Safety, feasibility and effects of an individualised walking intervention for
      women undergoing chemotherapy for ovarian cancer: a pilot study.
AB  - BACKGROUND: Exercise interventions during adjuvant cancer therapy have been shown
      to increase functional capacity, relieve fatigue and distress and may assist
      rates of chemotherapy completion. These studies have been limited to breast,
      gastric and mixed cancer groups and it is not yet known if a similar intervention
      is even feasible among women with ovarian cancer. We aimed to assess safety,
      feasibility and potential effect of a walking intervention in women undergoing
      chemotherapy for ovarian cancer. METHODS: Women newly diagnosed with ovarian
      cancer were recruited to participate in an individualised walking intervention
      throughout chemotherapy and were assessed pre- and post-intervention. Feasibility
      measures included session adherence, compliance with exercise physiologist
      prescribed walking targets and self-reported program acceptability. Changes in
      objective physical functioning (6-minute walk test), self-reported distress
      (Hospital Anxiety and Depression Scale), symptoms (Memorial Symptom Assessment
      Scale - Physical) and quality of life (Functional Assessment of Cancer Therapy -
      Ovarian) were calculated, and chemotherapy completion and adverse intervention
      effects recorded. RESULTS: Seventeen women were enrolled (63% recruitment rate).
      Mean age was 60 years (SD = 8 years), 88% were diagnosed with FIGO stage III or
      IV disease, 14 women underwent adjuvant and three neo-adjuvant chemotherapy. On
      average, women adhered to > 80% of their intervention sessions and complied with
      76% of their walking targets, with the majority walking four days a week at
      moderate intensity for 30 minutes per session. Meaningful improvements were found
      in physical functioning, physical symptoms, physical well-being and ovarian
      cancer-specific quality of life. Most women (76%) completed >=85% of their
      planned chemotherapy dose. There were no withdrawals or serious adverse events
      and all women reported the program as being helpful. CONCLUSIONS: These positive
      preliminary results suggest that this walking intervention for women receiving
      chemotherapy for ovarian cancer is safe, feasible and acceptable and could be
      used in development of future work. TRIAL REGISTRATION: ACTRN12609000252213.

PMID- 21899779
TI  - Exploring the bases for a mixed reality stroke rehabilitation system, Part II:
      design of interactive feedback for upper limb rehabilitation.
AB  - BACKGROUND: Few existing interactive rehabilitation systems can effectively
      communicate multiple aspects of movement performance simultaneously, in a manner
      that appropriately adapts across various training scenarios. In order to address
      the need for such systems within stroke rehabilitation training, a unified
      approach for designing interactive systems for upper limb rehabilitation of
      stroke survivors has been developed and applied for the implementation of an
      Adaptive Mixed Reality Rehabilitation (AMRR) System. RESULTS: The AMRR system
      provides computational evaluation and multimedia feedback for the upper limb
      rehabilitation of stroke survivors. A participant's movements are tracked by
      motion capture technology and evaluated by computational means. The resulting
      data are used to generate interactive media-based feedback that communicates to
      the participant detailed, intuitive evaluations of his performance. This article
      describes how the AMRR system's interactive feedback is designed to address
      specific movement challenges faced by stroke survivors. Multimedia examples are
      provided to illustrate each feedback component. Supportive data are provided for
      three participants of varying impairment levels to demonstrate the system's
      ability to train both targeted and integrated aspects of movement. CONCLUSIONS:
      The AMRR system supports training of multiple movement aspects together or in
      isolation, within adaptable sequences, through cohesive feedback that is based on
      formalized compositional design principles. From preliminary analysis of the
      data, we infer that the system's ability to train multiple foci together or in
      isolation in adaptable sequences, utilizing appropriately designed feedback, can
      lead to functional improvement. The evaluation and feedback frameworks
      established within the AMRR system will be applied to the development of a novel
      home-based system to provide an engaging yet low-cost extension of training for
      longer periods of time.

PMID- 21899780
TI  - DNA secondary structure is influenced by genetic variation and alters
      susceptibility to de novo translocation.
AB  - BACKGROUND: Cumulative evidence suggests that DNA secondary structures impact DNA
      replication, transcription and genomic rearrangements. One of the best studied
      examples is the recurrent constitutional t(11;22) in humans that is mediated by
      potentially cruciform-forming sequences at the breakpoints, palindromic AT-rich
      repeats (PATRRs). We previously demonstrated that polymorphisms of PATRR
      sequences affect the frequency of de novo t(11;22)s in sperm samples from normal
      healthy males. These studies were designed to determine whether PATRR
      polymorphisms affect DNA secondary structure, thus leading to variation in
      translocation frequency. METHODS: We studied the potential for DNA cruciform
      formation for several PATRR11 polymorphic alleles using mobility shift analysis
      in gel electrophoresis as well as by direct visualization of the DNA by atomic
      force microscopy. The structural data for various alleles were compared with the
      frequency of de novo t(11;22)s the allele produced. RESULTS: The data indicate
      that the propensity for DNA cruciform structure of each polymorphic allele
      correlates with the frequency of de novo t(11;22)s produced (r = 0.77, P = 0.01).
      CONCLUSIONS: Although indirect, our results strongly suggest that the PATRR
      adopts unstable cruciform structures during spermatogenesis that act as
      translocation hotspots in humans.

PMID- 21899781
TI  - Paradoxical euthyroid hormone profile in a case of Graves' disease with cardiac
      failure.
AB  - Cardiac failure is an uncommon complication of juvenile hyperthyroidism. We
      describe an adolescent boy with Graves' disease who developed manifestations of
      heart failure while on antithyroid medications. There was no evidence of any
      underlying cardiac disease. He had paradoxical euthyroid hormone profile which
      rose to hyperthyroid range when the manifestations of the cardiac failure
      subsided. The case highlights several unusual features of Graves' disease.

PMID- 21899782
TI  - Identification of factors associated with good response to growth hormone therapy
      in children with short stature: results from the ANSWER Program(r).
AB  - OBJECTIVE: To identify factors associated with growth in children on growth
      hormone (GH) therapy using data from the American Norditropin Studies: Web
      enabled Research (ANSWER) Program(r) registry. METHODS: GH-naive children with GH
      deficiency, multiple pituitary hormone deficiency, idiopathic short stature,
      Turner syndrome, or a history of small for gestational age were eligible (N =
      1,002). Using a longitudinal statistical approach, predictive factors were
      identified in patients with GHD for change from baseline in height standard
      deviation score (DeltaHSDS) following 2 years of treatment. RESULTS: Gradual
      increases in DeltaHSDS over time were observed for all diagnostic categories.
      Significant predictive factors of DeltaHSDS, ranked by significance were: height
      velocity (HV) at 4 months > baseline age > baseline HSDS > baseline body mass
      index (BMI) SDS > baseline insulin-like growth factor I (IGF-I) SDS; gender was
      not significant. HV at 4 months and baseline BMI SDS were positively correlated,
      whereas baseline age, HSDS, and IGF-I SDS were negatively correlated with
      DeltaHSDS. CONCLUSIONS: These results may help guide GH therapy based on
      pretreatment characteristics and early growth response.

PMID- 21899783
TI  - Don't sue the surgeon: remineralisation of the skull base or a defect that never
      existed?
AB  - INTRODUCTION: Intracranial complications are recognised as rare, but serious,
      sequelae of endoscopic sinus surgery. CASE REPORT: A 56-year-old woman was
      referred after developing meningitis following elective functional endoscopic
      sinus surgery. Computed tomography demonstrated a significant defect of the skull
      base in the right posterior ethmoid, clearly visible on both coronal and sagittal
      sections. Operative exploration demonstrated the skull base to be intact in the
      posterior ethmoid area identified on the scan, and the overlying mucosa appeared
      undisturbed. Scans were reviewed in the light of operative findings; coronal and
      sagittal images were found to be reconstructions. Directly acquired coronal
      computed tomography, undertaken three weeks after surgery, demonstrated a
      complete bony plate in the right posterior ethmoid at the site previously
      identified as dehiscent. DISCUSSION AND CONCLUSION: We speculate that the
      posterior ethmoid defect was actually an artefact of reconstruction. We cannot
      exclude the alternative possibility of remineralisation, but given the time frame
      this seems unlikely. This case highlights the need for caution when interpreting
      reconstructed images of the thin bony plates of the skull base and lamina
      papyracea, as regards both clinical significance and medicolegal reporting. While
      virtual defects have been reported in the superior semicircular canals as a
      result of reconstructed images, we believe this to be the first reported case
      demonstrating a similar problem in the anterior skull base.

PMID- 21899784
TI  - YouTube resources for the otolaryngology trainee.
AB  - Contemporary surgical training faces many challenges. However, modern technology,
      including internet-based resources, provides the trainee with a wealth of
      materials to complement their traditional teaching. YouTube is an online
      repository of video clips, and contains many instructional resources of value to
      the otolaryngology trainee.

PMID- 21899785
TI  - Prognostic role of epidermal growth factor-like domain 7 protein expression in
      laryngeal squamous cell carcinoma.
AB  - OBJECTIVE: This study aimed to retrospectively analyse the expression of
      epidermal growth factor-like domain 7 protein in cases of laryngeal squamous cell
      carcinoma. METHODS: We studied 116 patients retrospectively. Expression of
      epidermal growth factor-like domain 7 protein was determined in tumour and
      nontumour tissue samples, by immunohistochemistry. RESULTS: Expression levels
      were significantly increased in 94 cases. Increased expression levels correlated
      well with tumour stage (p = 0.001) and lymph node metastasis (p = 0.002). Log
      rank survival testing showed a significant difference between patients with
      marked versus limited expression levels (p = 0.03). Multivariable Cox regression
      analysis showed that epidermal growth factor-like domain 7 protein expression
      level was an independent predictor of laryngeal squamous cell carcinoma
      prognosis. CONCLUSION: These findings provide evidence that increased epidermal
      growth factor-like domain 7 protein expression is associated with laryngeal
      squamous cell carcinoma stage, lymph node metastasis and poor survival. This
      suggests that this protein may be a potential marker for laryngeal squamous cell
      carcinoma.

PMID- 21899786
TI  - Measures of the home environment related to childhood obesity: a systematic
      review.
AB  - OBJECTIVE: Due to a proliferation of measures for different components of the
      home environment related to childhood obesity, the purpose of the present
      systematic review was to examine these tools and the degree to which they can
      validly and reliably assess the home environment. DESIGN: Relevant manuscripts
      published between 1998 and 2010 were obtained through electronic database
      searches and manual searches of reference lists. Manuscripts were included if the
      researchers reported on a measure of the home environment related to child eating
      and physical activity (PA) and childhood obesity and reported on at least one
      psychometric property. RESULTS: Of the forty papers reviewed, 48 % discussed some
      aspect of parenting specific to food. Fifty-per cent of the manuscripts measured
      food availability/accessibility, 18 % measured PA availability/accessibility, 20
      % measured media availability/accessibility, 30 % focused on feeding style, 23 %
      focused on parenting related to PA and 20 % focused on parenting related to
      screen time. CONCLUSIONS: Many researchers chose to design new measures for their
      studies but often the items employed were brief and there was a lack of
      transparency in the psychometric properties. Many of the current measures of the
      home food and PA environment focus on one or two constructs; more comprehensive
      measures as well as short screeners guided by theoretical models are necessary to
      capture influences in the home on food and PA behaviours of children. Finally,
      the current measures of the home environment do not necessarily translate to
      specific sub-populations. Recommendations were made for future validation of
      measures in terms of appropriate psychometric testing.

PMID- 21899787
TI  - A bean-free diet increases the risk of all-cause mortality among Taiwanese women:
      the role of the metabolic syndrome.
AB  - OBJECTIVE: To evaluate the associations with chronic disease risk and mortality
      of the consequences of bean-free diets in Taiwanese adults with regard to gender.
      DESIGN: A sub-sample of the National Health Interview Survey (NHIS) in 2001
      agreed to physical examination in the subsequent year. This group then took part
      in the Taiwanese Survey of Hyperglycaemia, Hyperlipidaemia and Hypertension
      (TwSHHH) in 2002. SETTING: Individual records were linked to the eventual death
      files from 2002 to 2008. SUBJECTS: Up to the end of 2008, a total of 2820 men and
      2950 women were tracked by death registry over the 6.8 years of follow-up.
      RESULTS: Among 38,077 person-years, an average follow-up 6.5 years, 225 all-cause
      deaths were identified. Generalized linear models showed beans to be favourable
      for metabolic syndrome (other than for fasting glucose) in men; in women, beans
      were favourable for waist circumference and HbA1c. Cumulative logistic regression
      models for the effect of a bean-free diet on metabolic syndrome scores according
      to the Taiwanese-modified National Cholesterol Education Program-Adult Treatment
      Panel III (NCEP-tw) gave adjusted odds ratios of 1.83 in men and 1.45 in women.
      Cox regression models for the bean-free diet showed an increased hazard ratio for
      all-cause mortality among women (1.98, 95% CI 1.03, 3.81) but not men (1.28, 95%
      CI 0.76, 2.16). CONCLUSIONS: A bean-free diet may play a role in developing the
      metabolic syndrome in both genders, and is a significant predictor of all-cause
      mortality in Taiwanese women but not men.

PMID- 21899788
TI  - Reference curves for BMI, waist circumference and waist-to-height ratio for
      Azorean adolescents (Portugal).
AB  - OBJECTIVE: There are no percentile curves for BMI, waist circumference (WC) or
      waist-to-height ratio (WHtR) available for Portuguese children and adolescents.
      The purpose of the present study was to develop age- and sex-specific BMI, WC and
      WHtR percentile curves for a representative sample of adolescents living in the
      Portuguese islands of Azores, one of the poorest regions of Europe, and to
      compare them with those from other countries. DESIGN: Cross-sectional school
      based study. Weight, height and WC were objectively measured according to
      standard procedures. Smoothed percentile curves were estimated using Cole's LMS
      method. SETTING: Azores, Portugal. SUBJECTS: Proportionate stratified random
      sample of 1500 adolescents, aged 15-18 years. RESULTS: Results showed some sex
      differences in the shape of the BMI curves: in girls, the upper percentile values
      tend to decrease by the age of 16 and 17 years; whereas in boys, the upper
      percentiles tend to be flat between 15 and 16 years and then increase until the
      age of 18 years. In both sexes, the upper percentile values of both WC and WHtR
      decreased slightly by the age of 16 years and then increased steeply. In both
      sexes, the Azorean values for the 50th and 90th WC percentiles were higher than
      those reported for adolescents from the majority of other countries. CONCLUSIONS:
      The reference curves presented herein provide baseline data for the long-term
      surveillance of Azorean adolescents, as well as for national and international
      comparisons.

PMID- 21899789
TI  - The quality of midday meals eaten at school by adolescents; school lunches
      compared with packed lunches and their contribution to total energy and nutrient
      intakes.
AB  - OBJECTIVE: To compare food and nutrient intakes from midday meals provided by
      schools with those from packed lunches and to estimate the contribution from food
      eaten at midday to the total daily energy and nutrient intakes of teenagers.
      DESIGN: Dietary data were recorded in 4 d estimated diaries of which 2 d were
      school days. The school day data were analysed for total and midday energy and
      nutrient intakes. The latter were compared with the recommendations of the
      Caroline Walker Trust (CWT). SETTING: Cambridgeshire, UK, 2006. SUBJECTS:
      Teenagers (n 757) aged 14-15 years, from eighteen secondary schools, who reported
      food eaten at school. RESULTS: The contribution to total daily energy intake from
      all lunches eaten at school was 29 % (boys) and 28 % (girls). School meals
      provided greater quantities of protein, starch, carotene and folate but also more
      saturated fats and Na than packed lunches. Intakes of energy and several
      nutrients fell below the CWT recommendations for both types of lunch. School
      meals and packed lunches provided different types of foods; greater quantities of
      rice, pasta and vegetables in school meals; more yoghurt, cheese, fruit and
      juices but also more confectionery and soft drinks in packed lunches.
      CONCLUSIONS: There has been concern that schoolchildren who are not opting for
      lunch provided by schools are compromising the overall quality of their diet, but
      the present study showed small differences in nutrient content between packed and
      school lunches. These data were collected in 2005-2007 before the government
      programme of improvements reached secondary schools.

PMID- 21899790
TI  - Breakfast consumption and daily physical activity in 9-10-year-old British
      children.
AB  - OBJECTIVE: To examine the association between breakfast consumption and physical
      activity in a well-characterised sample of English children. DESIGN: Cross
      sectional study using food diaries to record breakfast consumption and
      accelerometry to assess physical activity. SETTING: Norfolk county, England.
      SUBJECTS: Children (n 1697) aged 9-10 years from the SPEEDY (Sport, Physical
      Activity and Eating behaviour: Environmental Determinants in Young people) study.
      RESULTS: Boyswho consumed a poor-quality breakfast based on dairy product, cereal
      and fruit intakes spent approximately 7 min more time in moderate-to-vigorous
      physical activity (MVPA) during weekday afternoons and evenings compared with
      those who did not consume breakfast (P,0?05). On weekend days, boys who consumed
      a poor- or good-quality breakfast spent approximately 6 and 5min less time
      respectively being sedentary during the mornings compared with breakfast
      nonconsumers (P,0?05). Boys who consumed a good-quality breakfast spent almost
      3min more in MVPA during the morning on weekend days compared with nonconsumers,
      and boys who consumed a poor- or good-quality breakfast were 22% and 16% more
      active overall respectively than breakfast non-consumers (P,0?05). During the
      rest of the day, boys who consumed a good-quality breakfast spent about 11 min
      less time being sedentary (P,0?05) and 7minmore time in MVPA (P,0?01).
      CONCLUSIONS: Although some associations between breakfast consumption and
      physical activity were detected for boys, the present study does not provide
      strong evidence that failing to consume breakfast, or having a low energy intake
      at breakfast time, is detrimental to children's physical activity levels.

PMID- 21899791
TI  - Food insecurity among adults residing in disadvantaged urban areas: potential
      health and dietary consequences.
AB  - OBJECTIVE: Food insecurity is the limited or uncertain availability or access to
      nutritionally adequate, culturally appropriate and safe foods. Food insecurity
      may result in inadequate dietary intakes, overweight or obesity and the
      development of chronic disease. Internationally, few studies have focused on the
      range of potential health outcomes related to food insecurity among adults
      residing in disadvantaged locations and no such Australian studies exist. The
      objective of the present study was to investigate associations between food
      insecurity, sociodemographic and health factors and dietary intakes among adults
      residing in disadvantaged urban areas. DESIGN: Data were collected by mail survey
      (n 505, 53 % response rate), which ascertained information about food security
      status, demographic characteristics (such as age, gender, household income,
      education) fruit and vegetable intakes, takeaway and meat consumption, general
      health, depression and chronic disease. SETTING: Disadvantaged suburbs of
      Brisbane city, Australia, 2009. SUBJECTS: Individuals aged >= 20 years. RESULTS:
      Approximately one in four households (25 %) was food insecure. Food insecurity
      was associated with lower household income, poorer general health, increased
      health-care utilisation and depression. These associations remained after
      adjustment for age, gender and household income. CONCLUSIONS: Food insecurity is
      prevalent in urbanised disadvantaged areas in developed countries such as
      Australia. Low-income households are at high risk of experiencing food
      insecurity. Food insecurity may result in significant health burdens among the
      population, and this may be concentrated in socio-economically disadvantaged
      suburbs.

PMID- 21899792
TI  - Rewards can be used effectively with repeated exposure to increase liking of
      vegetables in 4-6-year-old children.
AB  - OBJECTIVE: To examine whether parents offering a sticker reward to their child to
      taste a vegetable the child does not currently consume is associated with
      improvements in children's liking and consumption of the vegetable. DESIGN: A
      randomized controlled trial evaluated the effectiveness of exposure only (EO) and
      exposure plus reward (E + R), relative to a control group, on children's liking
      and consumption of a target vegetable. Assessments were conducted at baseline and
      2 weeks from baseline (post-intervention). Follow-up assessments were conducted
      at 4 weeks and 3 months from baseline. SETTING: The study took place in Adelaide,
      South Australia. Participants were self-selected in response to local media
      advertisements seeking to recruit parents finding it difficult to get their
      children to eat vegetables. SUBJECTS: Participants were 185 children (110 boys,
      seventy-five girls) aged 4-6 years and their primary caregiver/parent (172
      mothers, thirteen fathers). RESULTS: The E + R group was able to achieve more
      days of taste exposure. Both EO and E + R increased liking at post-intervention
      compared with control and no further change occurred over the follow-up period.
      All groups increased their intake of the target vegetable at post-intervention.
      Target vegetable consumption continued to increase significantly over the follow
      up period for E + R and control but not for EO. CONCLUSIONS: The findings provide
      support for the effectiveness of using a sticker reward with a repeated exposure
      strategy. In particular, such rewards can facilitate the actual tastings
      necessary to change liking.

PMID- 21899793
TI  - Who is missing the message? Targeting strategies to increase food label use among
      US adults.
AB  - OBJECTIVE: To evaluate the associations between sociodemographic and psychosocial
      characteristics and food label (FL) use in US adults. DESIGN: Data from the 1994
      1996 Continuing Survey of Food Intakes by Individuals and the Diet and Health
      Knowledge Survey were used. High socio-economic status (SES) was defined as >high
      school education and poverty-income ratio (PIR) >350 %, low SES as <high school
      level or PIR <130 %. Dietary intakes were assessed using 24 h recalls. SETTING:
      Metropolitan statistical area-central city, -suburban, and rural areas in the
      USA. SUBJECTS: US adults (n 2797; 1460 men, 1337 women) aged 20-64 years.
      RESULTS: Approximately 80 % of Americans reported using FL, including checking
      the nutrition panel, list of ingredients, short phrases, serving size, or health
      benefits. Only 26 % used all FL information. Compared with white women of higher
      SES, white men, black men and women with lower SES were 77-90 % less likely to
      use FL. Rural residents were 40 % less likely (OR = 0.60; 95 % CI 0.42, 0.86).
      Participants with good nutrition knowledge, perceptions and beliefs were twice as
      likely to check FL for nutrient content of foods (OR = 2.28; 95 % CI 1.53-3.40).
      Those who were unaware of diet-disease relationships were less likely to use FL
      (OR = 0.53; 95 % CI 0.32-0.85). Among overweight/obese Americans (BMI >= 25
      kg/m2), those who perceived their weight 'about right' were 51 % less likely to
      use FL than those perceiving themselves as overweight. CONCLUSIONS: Men,
      especially black men, women of low SES, rural residents and overweight Americans
      with inaccurate self-perception of body weight are less likely to use FL and
      should be targeted for increased intervention.

PMID- 21899794
TI  - Oxytocin and vasopressin genes are significantly associated with schizophrenia in
      a large Arab-Israeli pedigree.
AB  - We have previously studied the genetics of schizophrenia in a large inbred Arab
      Israeli pedigree and found evidence for linkage on chromosome 20p13. This locus
      harbours four strong candidate genes for schizophrenia: atractin (ATRN),
      pantonate-kinase2 (PANK2), oxytocin (OXT) and arginine-vasopressin (AVP). In this
      study we further explored the association of these genes with schizophrenia in
      the pedigree and searched for the disease-causing variants. A mutation screening
      of affected individuals from the pedigree was performed by using intensive
      sequencing in these four genes of interest. Then, we studied the prevalence of
      the identified variants in all family members (n=56) as well as in Arab-Israeli
      nuclear families (n=276) and a Jewish case-control sample (n=545). We also
      studied the possible functional role of these variants by examining their
      association with gene expression in the brain (n=104). We identified seven
      genetic variants in the OXT-AVP cluster in affected individuals from the
      pedigree. Three of these variants were significantly associated with
      schizophrenia in this pedigree. A 7-SNP haplotype was also significantly
      associated with disease. We found significant association of some of these
      variants in the two samples from the general population. Expression data analysis
      showed a possible functional role of two of these variants in regulation of gene
      expression. Involvement of OXT and AVP in the aetiology of schizophrenia has been
      suggested in the past. This study demonstrates, for the first time, a significant
      genetic association of these neuropeptides with schizophrenia and strongly
      supports this hypothesis. 

PMID- 21899795
TI  - Cannabis and cognitive performance in psychosis: a cross-sectional study in
      patients with non-affective psychotic illness and their unaffected siblings.
AB  - BACKGROUND: The relationship between cannabis use and cognitive functioning in
      patients with psychosis has yielded contradictory findings. In individuals at
      genetic high risk for psychosis, information is sparse. The aim of this study was
      to assess the association between recency and frequency of cannabis use and
      cognitive functioning in patients with psychosis and their unaffected siblings.
      METHOD: We conducted a cross-sectional study in 956 patients with non-affective
      psychosis, 953 unaffected siblings, and 554 control subjects. Participants
      completed a cognitive test battery including assessments of verbal learning, set
      shifting, sustained attention, processing speed, working memory, acquired
      knowledge, reasoning and problem solving and social cognition. Cannabis use was
      assessed by urinalysis and by the Composite International Diagnostic Interview.
      Using random-effect regression models the main effects of cannabis (recency and
      frequency) and the interaction with status (patient, sibling, control) on
      cognitive functioning were assessed. RESULTS: Current cannabis use was associated
      with poorer performance on immediate verbal learning, processing speed and
      working memory (Cohen's d -0.20 to -0.33, p<0.005). Lifetime cannabis use was
      associated with better performance on acquired knowledge, facial affect
      recognition and face identity recognition (Cohen's d+0.17 to +0.33, p<0.005).
      There was no significant interaction between cannabis and status on cognitive
      functioning. CONCLUSIONS: Lifetime cannabis-using individuals might constitute a
      subgroup with a higher cognitive potential. The residual effects of cannabis may
      impair short-term memory and processing speed.

PMID- 21899797
TI  - Natto and viscous vegetables in a Japanese-style breakfast improved insulin
      sensitivity, lipid metabolism and oxidative stress in overweight subjects with
      impaired glucose tolerance.
AB  - We previously suggested that the consumption of natto and viscous vegetables as
      part of a Japanese-style meal based on white rice (WR) reduced postprandial
      glucose and insulin levels in healthy subjects. The aim of the present study was
      to assess whether a single breakfast of natto and viscous vegetables or the same
      breakfast consumed for 2 weeks could improve glucose control, insulin
      sensitivity, lipid metabolism and oxidative stress in overweight subjects with
      impaired glucose tolerance (IGT). A total of eleven free-living subjects with IGT
      followed a randomised, crossover breakfast intervention for 2 weeks. The test
      meal included boiled WR with natto (viscous fermented soyabeans), Japanese yam
      and okra. The control meal included WR with non-viscous boiled soyabeans,
      potatoes and broccoli. Both meals contained comparable amounts of carbohydrate,
      fat, protein and fibre. The test meal reduced acute glucose and insulin responses
      compared to the control meal in the study participants. Insulin sensitivity was
      assessed using the composite insulin sensitivity index (CISI) after both the test
      and control meal periods. The test meal resulted in improvements in CISI compared
      to the baseline, whereas no significant changes were observed after the control
      meal period. Serum levels of both total and LDL-cholesterol were assessed before
      and after the test meal period and found to decrease significantly. There was
      also a tendency towards reduced serum malondialdehyde-modified LDL and N(E)
      carboxymethyllysine. No differences were observed in the measures of chronic
      glycaemic control. Thus, we conclude that a breakfast of natto and viscous
      vegetables consumed for 2 weeks improves insulin sensitivity, serum lipid and
      oxidative stress.

PMID- 21899798
TI  - Evaluation of the immune benefits of two probiotic strains Bifidobacterium
      animalis ssp. lactis, BB-12(r) and Lactobacillus paracasei ssp. paracasei, L.
      casei 431(r) in an influenza vaccination model: a randomised, double-blind,
      placebo-controlled study.
AB  - The present study investigated the ability of Bifidobacterium animalis ssp.
      lactis (BB-12(r)) and Lactobacillus paracasei ssp. paracasei (L. casei 431(r)) to
      modulate the immune system using a vaccination model in healthy subjects. A
      randomised, double-blind, placebo-controlled, parallel-group study was conducted
      in 211 subjects (56 % females, mean age 33.2 (sd 13.1) years). Subjects consumed
      a minimum of 109 colony-forming units of BB-12(r) (capsule) or L. casei 431(r)
      (dairy drink) or a matching placebo once daily for 6 weeks. After 2 weeks, a
      seasonal influenza vaccination was given. Plasma and saliva samples were
      collected at baseline and after 6 weeks for the analysis of antibodies, cytokines
      and innate immune parameters. Changes from baseline in vaccine-specific plasma
      IgG, IgG1 and IgG3 were significantly greater in both probiotic groups v. the
      corresponding placebo group (L. casei 431(r), P = 0.01 for IgG; P < 0.001 for
      remaining comparisons). The number of subjects obtaining a substantial increase
      in specific IgG (defined as >= 2-fold above baseline) was significantly greater
      in both probiotic groups v. placebo (BB-12(r), P < 0.001 for IgG, IgG1 and IgG3;
      L. casei 431(r), P < 0.001 for IgG1 and IgG3). Significantly greater mean fold
      increases for vaccine-specific secretory IgA in saliva were observed in both
      probiotic groups v. placebo (BB-12(r), P = 0.017; L. casei 431(r), P = 0.035).
      Similar results were observed for total antibody concentrations. No differences
      were found for plasma cytokines or innate immune parameters. Data herein show
      that supplementation with BB-12(r) or L. casei 431(r) may be an effective means
      to improve immune function by augmenting systemic and mucosal immune responses to
      challenge.

PMID- 21899800
TI  - Vitamin C and fibre consumption from fruits and vegetables improves oxidative
      stress markers in healthy young adults.
AB  - The aim of the present cross-sectional study was to assess the potential
      relationships between fruit and vegetable (FV) consumption and some oxidative
      stress markers in young adults, with particular emphasis on fibre and vitamin C
      intake. The study enrolled 246 healthy subjects (eighty-eight men and 158 women),
      with a mean age of 22 (sd 3) years and a mean BMI of 21.9 (sd 2.8) kg/m2. Dietary
      intake, anthropometry, blood pressure, lifestyle features and blood biochemical
      data were assessed with validated procedures. Those subjects in the highest
      tertile (T) of FV consumption ( >= 705 g/d) had statistically lower oxidised LDL
      (ox-LDL) concentrations as well as higher plasma total antioxidant capacity (TAC)
      and glutathione peroxidase (GPx) activity (P for trend <0.05), after adjusting
      for sex, age, energy intake, physical activity, smoking, BMI, vitamin supplement
      use and other confounding factors. Moreover, plasma ox-LDL concentrations showed
      a decreasing trend and TAC an increasing trend across tertiles of fibre (T3: >=14
      g/d) and vitamin C (T3: >=150 mg/d) from FV intake, while GPx activity was
      positively associated with vitamin C intake (P for trend < 0.05). In conclusion,
      greater FV consumption was independently associated with reduced ox-LDL as well
      as increased TAC and GPx activity in healthy young adults, with dietary fibre and
      vitamin C from FV clearly being implicated in this beneficial relationship.

PMID- 21899801
TI  - Marine collagen peptides protect against early alcoholic liver injury in rats.
AB  - Marine collagen peptides (MCP) have been reported to exhibit antioxidative
      activity, which is the common property of numerous hepatoprotective agents.
      Previous studies have shown that MCP have biological functions including anti
      hypertension, anti-ulcer, anti-skin ageing and extending the life span. However,
      its role in alcoholic liver injury remains unknown. The present study aimed to
      investigate the effects of MCP on early alcoholic liver injury in rats. Rats were
      administered with alcohol at a dose of 6 g/kg body weight intragastrically per d
      to induce early liver injury, which was then evaluated by serum markers and
      histopathological examination. Treatment with MCP could reverse the increased
      level of serum aminotransferase and reduce hepatic histological damage. In
      addition, MCP attenuated the alteration in serum superoxide dismutase and
      malondialdehyde levels. MCP also counteracted the increased levels of total
      cholesterol and TAG. However, no significant difference was observed in the
      contents of alcohol dehydrogenase both in liver and serum protein of rats. These
      findings suggest that MCP have a protective effect on early alcoholic liver
      injury in rats by their antioxidative activity and improving lipid metabolism.

PMID- 21899799
TI  - Dietary patterns and risk of oesophageal cancers: a population-based case-control
      study.
AB  - Epidemiological studies investigating the association between dietary intake and
      oesophageal cancer have mostly focused on nutrients and food groups instead of
      dietary patterns. We conducted a population-based case-control study, which
      included 365 oesophageal adenocarcinoma (OAC), 426 oesophagogastric junction
      adenocarcinoma (OGJAC) and 303 oesophageal squamous cell carcinoma (OSCC) cases,
      with frequency matched on age, sex and geographical location to 1580 controls.
      Data on demographic, lifestyle and dietary factors were collected using self
      administered questionnaires. We used principal component analysis to derive three
      dietary patterns: 'meat and fat', 'pasta and pizza' and 'fruit and vegetable',
      and unconditional logistic regression models to estimate risks of OAC, OGJAC and
      OSCC associated with quartiles (Q) of dietary pattern scores. A high score on the
      meat-and-fat pattern was associated with increased risk of all three cancers:
      multivariable-adjusted OR 2.12 (95 % CI 1.30, 3.46) for OAC; 1.88 (95% CI 1.21,
      2.94) for OGJAC; 2.84 (95% CI 1.67, 4.83) for OSCC (P-trend <0.01 for all three
      cancers). A high score on the pasta-and-pizza pattern was inversely associated
      with OSCC risk (OR 0.58, 95 % CI 0.36, 0.96, P for trend=0.009); and a high score
      on the fruit-and-vegetable pattern was associated with a borderline significant
      decreased risk of OGJAC (OR for Q4 v. Q1 0.66, 95% CI 0.42, 1.04, P=0.07) and
      significantly decreased risk of OSCC (OR 0.41, 95% CI 0.24, 0.70, P for
      trend=0.002). High-fat dairy foods appeared to play a dominant role in the
      association between the meat-and-fat pattern and risk of OAC and OGJAC. Further
      investigation in prospective studies is needed to confirm these findings.

PMID- 21899802
TI  - Western and Mediterranean dietary patterns among Balearic Islands' adolescents:
      socio-economic and lifestyle determinants.
AB  - OBJECTIVE: To assess prevailing food patterns among Balearic Islands'
      adolescents, and socio-economic and lifestyle determinants. DESIGN: Cross
      sectional nutritional survey carried out (2007-2008) in the Balearic Islands, a
      Mediterranean region. Dietary assessment was based on a 145-item semi
      quantitative FFQ and two non-consecutive 24 h recalls. Anthropometric
      measurements and questions related to socio-economic, lifestyle, physical
      activity and body image were assessed. SETTING: Data obtained from a
      representative sample of all inhabitants living in the Balearic Islands aged 12
      17 years. SUBJECTS: A random sample (n 1231) of the adolescent population (12-17
      years old) was interviewed. RESULTS: Factor analysis identified two major dietary
      food patterns: 'Western' and 'Mediterranean'. The 'Western' dietary pattern was
      higher among boys than girls, associated with spending >=4 h/d on media screen
      time, but less prevalent among those adolescents who desired a thinner body and
      those girls who desired to remain the same weight. The 'Mediterranean' dietary
      pattern was mainly followed by girls, and also boys who spent < 2 h/d on media
      screen time and girls with high parental socio-economic status. CONCLUSIONS: The
      present study shows the existence of two major dietary patterns among Balearic
      Islands' adolescents: 'Western' and 'Mediterranean', but girls are more
      'Mediterranean' than boys. This evidence supports that the food pattern of
      Balearic Islands' adolescents is in a transitional state characterised by the
      loss of the traditional Mediterranean dietary pattern towards a Western dietary
      pattern. Low parental socio-economic status, much leisure-time on sedentary
      behaviours such as media screen time and body image are factors associated with
      the 'Western' dietary pattern.

PMID- 21899804
TI  - Antihyperglycaemic activity of Asparagus racemosus roots is partly mediated by
      inhibition of carbohydrate digestion and absorption, and enhancement of cellular
      insulin action.
AB  - Asparagus racemosus roots have been shown to enhance insulin secretion in
      perfused pancreas and isolated islets. The present study investigated the effects
      of ethanol extracts of A. racemosus roots on glucose homeostasis in diabetic
      rats, together with the effects on insulin action in 3T3 adipocytes. When
      administered orally together with glucose, A. racemosus extract improved glucose
      tolerance in normal as well as in two types of diabetic rats. To investigate the
      possible effects on carbohydrate absorption, the sucrose content of the
      gastrointestinal tract was examined in 12 h fasted rats after an oral sucrose
      load (2.5 g/kg body weight). The extract significantly suppressed postprandial
      hyperglycaemia after sucrose ingestion and reversibly increased unabsorbed
      sucrose content throughout the gut. The extract also significantly inhibited the
      absorption of glucose during in situ gut perfusion with glucose. Furthermore, the
      extract enhanced glucose transport and insulin action in 3T3-L1 adipocytes. Daily
      administration of A. racemosus to type 2 diabetic rats for 28 d decreased serum
      glucose, increased pancreatic insulin, plasma insulin, liver glycogen and total
      oxidant status. These findings indicate that antihyperglycaemic activity of A.
      racemosus is partly mediated by inhibition of carbohydrate digestion and
      absorption, together with enhancement of insulin secretion and action in the
      peripheral tissue. Asparagus racemosus may be useful as a source of novel
      antidiabetic compounds or a dietary adjunct for the management of diabetes.

PMID- 21899803
TI  - The effects of micronutrient-fortified complementary/replacement food on
      intestinal permeability and systemic markers of inflammation among maternally HIV
      exposed and unexposed Zambian infants.
AB  - The present randomised trial investigated the effects of feeding Zambian infants
      from 6 to 18 months old either a richly or basal micronutrient-fortified
      complementary/replacement food on gut integrity and systemic inflammation. Blood
      samples were obtained from all infants (n 743) at 6 and 18 months for the
      assessment of serum C-reactive protein (CRP) and alpha1-acid glycoprotein (AGP).
      A subsample of 502 infants, selected from the main cohort to include a larger
      proportion of infants with HIV-positive mothers, was assigned to
      lactulose/mannitol gut permeability tests. Lactulose:mannitol (L:M) ratio
      analyses were adjusted for baseline urinary L:M ratio, socio-economic status,
      mother's education, season of birth and baseline stunting, and stratified by
      maternal antenatal HIV status, child's sex, concurrent breast-feeding status and
      anaemia at baseline. There was no significant difference in geometric mean L:M
      ratio between the richly fortified and basal-fortified porridge arms at 12 months
      (0.47 (95 % CI 0.41, 0.55) v. 0.41 (95 % CI 0.34, 0.49); P = 0.16 adjusted). At
      18 months, the richly fortified porridge group had a significantly higher
      geometric mean L:M ratio than the basal-fortified group (0.23 (95 % CI 0.19,
      0.28) v. 0.15 (95 % CI 0.12, 0.19); P = 0.02 adjusted). This effect was evident
      for all stratifications, significantly among boys (P = 0.04), among the infants
      of HIV-negative mothers (P = 0.01), among the infants of HIV-negative mothers not
      concurrently breast-fed (P = 0.01) and among those who were not anaemic at
      baseline (P = 0.03). CRP, but not AGP, was positively associated with L:M ratio,
      but there were no significant effects of the diet on either CRP or AGP. In
      conclusion, a richly fortified complementary/replacement food did not benefit and
      may have worsened intestinal permeability.

PMID- 21899806
TI  - Low concentrations of serum 25-hydroxyvitamin D associated with increased risk
      for chronic bronchitis among US adults.
AB  - Increasing evidence suggests that vitamin D benefits both innate and adaptive
      immunity, thereby eliciting an anti-inflammatory effect and reducing the risk of
      infectious disease. The present study examined the association between serum 25
      hydroxyvitamin D (25(OH)D) levels and the risk of chronic bronchitis among US
      adults. We analysed data from 6872 US adults aged >= 20 years who participated in
      the 2003-6 National Health and Nutrition Examination Survey. Prevalence and OR
      with 95 % CI of having self-reported chronic bronchitis were estimated by
      quintiles of 25(OH)D or vitamin D-deficiency status after adjustment for
      potential confounders. The results showed that the adjusted prevalence of chronic
      bronchitis ranged from 2.4 (95 % CI 1.4, 3.3) % among adults in the highest
      quintile of 25(OH)D ( >= 30 ng/ml) to 4.1 (95 % CI 2.5, 5.6) % among adults in
      the lowest quintile ( < 15 ng/ml; P for trend < 0.01). The adjusted OR for
      chronic bronchitis was 1.85 (95 % CI 1.06, 3.24) in adults with < 15 ng/ml
      25(OH)D and 1.77 (95 % CI 1.19, 2.65) in those with 15 to < 20 ng/ml 25(OH)D
      compared with adults with >= 30 ng/ml 25(OH)D. Additionally, the adjusted OR for
      chronic bronchitis was 1.52 (95 % CI 1.03, 2.26) among adults with vitamin D
      deficiency ( < 20 ng/ml 25(OH)D) compared with those with >= 20 ng/ml 25(OH)D.
      For every 1 ng/ml increase in 25(OH)D, the likelihood of having chronic
      bronchitis fell by 2.6 % (P = 0.016). In conclusion, low serum 25(OH)D levels are
      associated with the increased risk of chronic bronchitis among US adults. The
      present results provide support for continuing research on the role of vitamin D
      in lung diseases.

PMID- 21899805
TI  - Lutein and zeaxanthin intake and the risk of age-related macular degeneration: a
      systematic review and meta-analysis.
AB  - Lutein and zeaxanthin are thought to decrease the incidence of age-related
      macular degeneration (AMD); however, findings have been inconsistent. We
      conducted a systematic literature review and meta-analysis to evaluate the
      relationship between dietary intake of lutein and zeaxanthin and AMD risk.
      Relevant studies were identified by searching five databases up to April 2010.
      Reference lists of articles were retrieved, and experts were contacted.
      Literature search, data extraction and study quality assessment were performed
      independently by two reviewers and results were pooled quantitatively using meta
      analysis methods. The potential sources of heterogeneity and publication bias
      were also estimated. The search yielded six longitudinal cohort studies. The
      pooled relative risk (RR) for early AMD, comparing the highest with the lowest
      category of lutein and zeaxanthin intake, was 0.96 (95 % CI 0.78, 1.17). Dietary
      intake of these carotenoids was significantly related with a reduction in risk of
      late AMD (RR 0.74; 95 % CI 0.57, 0.97); and a statistically significant inverse
      association was observed between lutein and zeaxanthin intake and neovascular AMD
      risk (RR 0.68; 95 % CI 0.51, 0.92). The results were essentially consistent among
      subgroups stratified by participant characteristics. The findings of the present
      meta-analysis indicate that dietary lutein and zeaxanthin is not significantly
      associated with a reduced risk of early AMD, whereas an increase in the intake of
      these carotenoids may be protective against late AMD. However, additional studies
      are needed to confirm these relationships.

PMID- 21899807
TI  - Relative validity of a FFQ in measuring carbohydrate fractions, dietary glycaemic
      index and load: exploring the effects of subject characteristics.
AB  - FFQ require validation as part of epidemiological research of diet-disease
      relationships. Studies exploring associations between carbohydrate type and
      chronic diseases are rapidly increasing, but information on the validity of
      carbohydrate fractions, dietary glycaemic index (GI) and the glycaemic load (GL)
      estimated by FFQ is scarce. Likewise, the effects of subject characteristics on
      FFQ validity have been poorly documented. The present study evaluates the
      relative validity of an 131-item FFQ in relation to two 3 d food records (FR)
      performed 6 months apart focusing on the intake of carbohydrate fractions,
      dietary GI and the GL. Furthermore, we assessed the extent to which subjects'
      age, education and BMI explain differences between these methods. The study
      sample comprised 218 men and 292 women aged 25-74 years participating in a large
      population-based survey in Finland. Energy-adjusted Spearman's rank correlations
      ranged from 0.27 (sugars) to 0.70 (lactose) for men and from 0.37 (sugars) to
      0.69 (lactose) for women. On average, 73 % of the subjects were categorised into
      the same or adjacent distribution quintile based on the two methods. In general,
      the FFQ overestimated the intakes compared with FR. Especially in women, FFQ
      validity for some nutrients was associated with the level of intake, subjects'
      age and, to a lesser extent, education but not BMI. In conclusion, the FFQ
      appears to be reasonably valid in the assessment of carbohydrate exposure
      variables, but the findings show a need for adjustment of diet-disease
      relationships for subjects' age and education.

PMID- 21899808
TI  - Paranasal sinus computed tomography anatomy: a surgeon's perspective.
AB  - Computed tomography scans serve as a critical 'roadmap' for functional endoscopic
      sinus surgery. A systematic evaluation of such scans, and an awareness of any
      anatomical variants that may modify one's surgical approach, allow one to pre
      empt complications. This article describes, from a novice's perspective, two
      methods of evaluating paranasal sinus computed tomography scans: a quick
      assessment technique; and a step-wise, operative approach covering radiological
      features relevant to pre- and peri-operative management.

PMID- 21899809
TI  - Closed-cell foam skin thickness measurement using a scanning electron microscope.
AB  - Closed cell polymer foam skin thickness can be assessed by taking backscatter
      electron (BSE) images in a scanning electron microscope (SEM) at a series of
      accelerating voltages. Under a given set of experimental conditions, the electron
      beam mostly passes through thin polymer skin cell walls. That cell appears dark
      compared to adjacent thicker-skinned cells. Higher accelerating voltages lead to
      a thicker skin being penetrated. Monte Carlo modeling of beam-sample interactions
      indicates that at 5 keV, skin less than ~0.5 MUm in thickness will appear dark,
      whereas imaging at 30 keV allows skin thicknesses up to ~4 MUm to be identified.
      The distribution of skin thickness can be assessed over square millimeters of
      foam surface in this manner. Qualitative comparisons of the skin thicknesses of
      samples can be made with a simple visual inspection of the images. A
      semiquantitative comparison is possible by applying image analysis. The proposed
      method is applied to two example foams. Characterizing foam skin thickness by
      this method is possible using any SEM that is capable of collecting useful BSE
      images over a range of accelerating voltages. Imaging in low vacuum, where an
      electrically conductive metal coating is not required, leads to more sensitivity
      in skin thickness characterization.

PMID- 21899810
TI  - Electron image series reconstruction of twin interfaces in InP superlattice
      nanowires.
AB  - The twin interface structure in twinning superlattice InP nanowires with
      zincblende structure has been investigated using electron exit wavefunction
      restoration from focal series images recorded on an aberration-corrected
      transmission electron microscope. By comparing the exit wavefunction phase with
      simulations from model structures, it was possible to determine the twin
      structure to be the ortho type with preserved In-P bonding order across the
      interface. The bending of the thin nanowires away from the intended 110 axis
      could be estimated locally from the calculated diffraction pattern, and this
      parameter was successfully taken into account in the simulations.

PMID- 21899811
TI  - Minerals and aligned collagen fibrils in tilapia fish scales: structural analysis
      using dark-field and energy-filtered transmission electron microscopy and
      electron tomography.
AB  - The mineralized structure of aligned collagen fibrils in a tilapia fish scale was
      investigated using transmission electron microscopy (TEM) techniques after a thin
      sample was prepared using aqueous techniques. Electron diffraction and electron
      energy loss spectroscopy data indicated that a mineralized internal layer
      consisting of aligned collagen fibrils contains hydroxyapatite crystals. Bright
      field imaging, dark-field imaging, and energy-filtered TEM showed that the
      hydroxyapatite was mainly distributed in the hole zones of the aligned collagen
      fibrils structure, while needle-like materials composed of calcium compounds
      including hydroxyapatite existed in the mineralized internal layer. Dark-field
      imaging and three-dimensional observation using electron tomography revealed that
      hydroxyapatite and needle-like materials were mainly found in the matrix between
      the collagen fibrils. It was observed that hydroxyapatite and needle-like
      materials were preferentially distributed on the surface of the hole zones in the
      aligned collagen fibrils structure and in the matrix between the collagen fibrils
      in the mineralized internal layer of the scale.

PMID- 21899812
TI  - EVerT: cryotherapy versus salicylic acid for the treatment of verrucae--a
      randomised controlled trial.
AB  - OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of
      cryotherapy using liquid nitrogen versus patient daily self-treatment with 50%
      salicylic acid for the treatment of verrucae (plantar warts). DESIGN: A
      multicentre, pragmatic, open, two-armed randomised controlled trial with an
      economic evaluation. Randomisation was simple, with the allocation sequence
      generated by a computer in a 1 : 1 ratio. SETTING: Podiatry clinics, university
      podiatry schools and primary care in England, Scotland and Ireland. PARTICIPANTS:
      Patients were eligible if they presented with a verruca which, in the opinion of
      the health-care professional, was suitable for treatment with both salicylic acid
      and cryotherapy, and were aged 12 years and over. INTERVENTIONS: Cryotherapy
      using liquid nitrogen delivered by a health-care professional compared with daily
      patient self-treatment with 50% salicylic acid (Verrugon, William Ransom & Son
      Plc, Hitchin, UK) for a maximum of 8 weeks. MAIN OUTCOME MEASURES: The primary
      outcome was complete clearance of all verrucae at 12 weeks. Secondary outcomes
      were complete clearance of all verrucae at 12 weeks, controlling for age, whether
      or not the verrucae had been previously treated and type of verrucae, with a
      second model to explore the effect of patient preferences, time to clearance of
      verrucae, clearance of verrucae at 6 months, number of verrucae at 12 weeks and
      patient satisfaction with the treatment. RESULTS: In total, 240 eligible patients
      were recruited, with 117 patients allocated to the cryotherapy group and 123 to
      the salicylic acid group. There was no evidence of a difference in clearance
      rates between the treatment groups in the primary outcome [17/119 (14.3%) in the
      salicylic acid group vs 15/110 (13.6%) in the cryotherapy group; p = 0.89]. The
      results of the study did not change when controlled for age, whether or not the
      verrucae had been previously treated and type of verrucae, or when patient
      preferences were explored. There was no evidence of a difference in time to
      clearance of verrucae between the two groups [hazard ratio (HR) 0.80, 95%
      confidence interval (CI) 0.51 to 1.25; p = 0.33] or in the clearance of verrucae
      at 6 months (33.7% cryotherapy vs 30.5% salicylic acid). There was no evidence of
      a difference in the number of verrucae at 12 weeks between the two groups
      (incidence rate ratio 1.08, 95% CI 0.81 to 1.43; p = 0.62). Nineteen participants
      reported 28 adverse events, 14 in each group, with two treatment-related non
      serious adverse events in the cryotherapy group. Cryotherapy was also associated
      with higher mean costs per additional healed patient (L101.17, 95% bias-corrected
      and accelerated CI L85.09 to L117.26). The probability of cryotherapy being cost
      effective is 40% for a range of willingness-to-pay thresholds of L15,000-30,000
      per patient healed. CONCLUSIONS: There is no evidence for a difference in terms
      of clearance of verrucae between cryotherapy and salicylic acid (at both 12 weeks
      and 6 months), number of verrucae at 12 weeks and time to clearance of verrucae.
      Cryotherapy was associated with higher mean costs per additional healed patient
      compared with salicylic acid. TRIAL REGISTRATION: Current Controlled Trials
      ISRCTN18994246. FUNDING: This project was funded by the NIHR Health Technology
      Assessment programme and will be published in full in Health Technology
      Assessment; Vol. 15, No. 32. See the HTA programme website for further project
      information.

PMID- 21899813
TI  - Evidence for the use of l-methylfolate combined with antidepressants in MDD.
AB  - Helping patients with major depressive disorder achieve symptom-free remission
      with antidepressant therapy remains challenging. In this activity, 3
      investigators discuss the results of a 2-trial, multicenter, randomized, double
      blind, placebo-controlled study of adjunctive l-methylfolate, the bioavailable
      form of folate, in patients who had inadequately responded to an SSRI. The
      efficacy of doses of 7.5 mg/d versus 15 mg/d is examined, and the safety and
      tolerability of l-methylfolate are compared with those of other adjunctive
      treatments. Different types of folate are explained, and the characteristics of
      patients who might benefit from adjunctive l-methylfolate are proposed.

PMID- 21899814
TI  - Safety and tolerability of antipsychotic treatment in young patients with
      schizophrenia.
AB  - Antipsychotics have proven efficacy for treating patients with early-onset
      schizophrenia, and aripiprazole, olanzapine, quetiapine, and risperidone have FDA
      approval for treating adolescents aged 13 to 17 years. Children and adolescents
      appear to have a higher risk than adults for experiencing adverse events such as
      extrapyramidal symptoms, prolactin elevation, weight gain, and metabolic effects
      when taking antipsychotic medications. Pediatric studies indicate that adverse
      effect profiles differ among commonly used antipsychotics. Clinicians should
      consider the differing adverse effect profiles when choosing medications for
      young patients.

PMID- 21899815
TI  - Selecting appropriate treatment for patients who are nonresponsive to initial
      therapy.
AB  - Depression can be a chronic illness, and several treatment steps are often needed
      to achieve sustained symptom remission and return patients to premorbid levels of
      functioning. Patients with chronic depressive illness, early onset, concurrent
      psychiatric or medical conditions, difficult psychosocial problems, or comorbid
      melancholic and anxious features may require additional treatment steps. Next
      step strategies, after optimizing the dose and extending the treatment trial of
      the initial antidepressant, include switching antidepressants, adding another
      antidepressant, and augmenting with a nonantidepressant agent.

PMID- 21899816
TI  - PTSD comorbidity and suicidal ideation associated with PTSD within the Ohio Army
      National Guard.
AB  - OBJECTIVE: To study the relation between posttraumatic stress disorder (PTSD)
      psychiatric comorbidity and suicidal ideation in a representative sample of Ohio
      Army National Guard soldiers. METHOD: Using retrospective data collected on the
      telephone from a random sample of 2,616 National Guard soldiers who enrolled in a
      10-year longitudinal study (baseline data collected November 2008-November 2009),
      we examined (1) the prevalence of other psychopathologies among those with DSM-IV
      diagnosed PTSD compared to those without PTSD and (2) the association between
      PTSD comorbidity and suicidal ideation (reporting thoughts of being better off
      dead or hurting themselves). All analyses were carried out using logistic
      regression. RESULTS: Of guard members with PTSD in the last year, 61.7% had at
      least 1 other psychopathology; 20.2% had at least 2 other co-occurring
      conditions. The most common co-occurring psychopathology was depression. While
      those with PTSD overall were 5.4 (95% CI, 3.8-7.5) times more likely to report
      suicidality than those without PTSD, those who had at least 2 additional
      conditions along with PTSD were 7.5 (95% CI, 3.0-18.3) times more likely to
      report suicidal ideation at some point in their lifetime than those with PTSD
      alone. CONCLUSIONS: Soldiers with PTSD were at increased risk for suicidality,
      and, among those with PTSD, those with at least 2 additional conditions were at
      the highest risk of suicidal ideation. Future research should address the
      mechanisms that contribute to multimorbidity in this population and the
      appropriate treatment methods for this high-risk group.

PMID- 21899817
TI  - The prevalence and comorbidity of social anxiety disorder among United States
      Latinos: a retrospective analysis of data from 2 national surveys.
AB  - OBJECTIVE: Social anxiety disorder (SAD) is increasingly being recognized as a
      prevalent, unremitting, and highly comorbid disorder, yet studies focusing on
      this disorder among US Latinos and immigrant populations are not available. This
      article evaluates ethnic differences in the prevalence and comorbidity of SAD as
      well as the clinical and demographic characteristics associated with SAD.
      Cultural and contextual factors associated with risk of SAD are also examined
      within the Latino population more specifically. METHOD: Data are analyzed from
      the National Latino and Asian American Study and the National Comorbidity Survey
      Replication. Both studies utilized the World Health Organization-Composite
      International Diagnostic Interview, which estimates the prevalence of lifetime
      and 12-month psychiatric disorders according to DSM-IV criteria. RESULTS: Latinos
      reported a lower lifetime and 12-month SAD prevalence and a later age at onset
      than US-born non-Latino whites. On the other hand, Latinos diagnosed with 12
      month SAD reported higher impairment across home, work, and relationship domains
      than their non-Latino white counterparts. Relative to non-Latino whites, Latinos
      who entered the United States after the age of 21 years were less likely to have
      lifetime SAD comorbidity with drug abuse and dependence and more likely to report
      lifetime SAD comorbidity with agoraphobia. CONCLUSIONS: The pattern of risk and
      associated characteristics of SAD varies for Latinos as compared to non-Latino
      whites. This is reflected by differences between these 2 groups across SAD
      prevalence, onset, impairment, and comorbidity. The particularly high comorbidity
      found with agoraphobia among Latinos who arrive in the United States as adults
      suggests that cultural factors and timing of immigration play a role in the
      manifestation and course of anxiety disorders. Interventions designed to decrease
      the levels of impairment associated with SAD are needed as well as efforts to
      target Latinos suffering from this disorder, specifically.

PMID- 21899818
TI  - Assessing the adequacy of past antidepressant trials: a clinician's guide to the
      antidepressant treatment response questionnaire.

PMID- 21899820
TI  - Treatment outcome for bereavement-excluded depression: results of the study by
      Corruble et al are not what they seem.

PMID- 21899821
TI  - Searching for serendipity.

PMID- 21899824
TI  - Exposure histories derived from selenium in otoliths of three cold-water fish
      species captured downstream from coal mining activity.
AB  - Establishing exposure to contaminants within a given environment is often
      difficult for fish species with large home ranges. Chemical analyses of muscle or
      visceral tissue are useful indicators of recent exposure, but depuration,
      metabolic transformation, and tissue redistributions can alter temporal
      resolution. Otoliths are metabolically stable and thus provide complete chemical
      records within their calcified tissues that, when coupled to the annular
      structure, can provide temporal resolution for exposure to trace metals. Otoliths
      from bull trout, cutthroat trout, and mountain whitefish from an area rich in
      seleniferous soils and with active coal mining activity were analyzed for
      selenium to determine any history of exposure to elevated levels of selenium.
      Selenium concentrations in otolith primordia tended to be low, indicating that
      these fish emerged in low selenium areas. Later life stages showed peaks of high
      Se concentrations, suggesting that individuals moved into areas of increased
      selenium later in life. Individuals captured from the same area had a wide
      variety of selenium exposure profiles, indicating that these fish do not move en
      masse into and out of high-selenium areas. Year-to-year variability of selenium
      exposure patterns within an otolith suggests inconsistent utilization of high-
      and low-selenium areas by the individual. The inconsistent exposure profiles for
      these fish, in addition to their home range of tens of kilometres, indicate that
      soft tissue concentrations, while useful indicators of recent exposure, cannot be
      relied upon to provide a life history recording of exposure.

PMID- 21899825
TI  - Risks of seawater ozonation in recirculation aquaculture--effects of oxidative
      stress on animal welfare of juvenile turbot (Psetta maxima, L.).
AB  - Ozone is frequently used for water treatment and disinfection in recirculating
      aquaculture systems. However, due to the fragmentary data on chronic toxicity of
      ozone produced oxidants (OPO) and its safe concentrations, the daily application
      of ozone in aquaculture is challenging. To evaluate the chronic effects of
      sublethal OPO concentrations, juvenile turbot (Psetta maxima, L.) were exposed to
      OPO concentrations of 0.06, 0.10 and 0.15 mg/l for 21 days. Gills were analysed
      for histopathological alterations and mRNA expression of heat shock protein 70
      (hsp70), hsp90 as well as glutathione-S-transferase (gst) were determined in the
      gills and the liver after 1d, 7d and 21 d. Histopathologic findings confirmed
      adverse effects at 0.10-0.15 mg/l, but these (necrosis, lamellar clubbing,
      hypertrophy, hyperplasia) could only be observed after an extended exposure
      (mostly 21 d), and were considered as irreversible tissue damage. Hsp70
      expression in the gills was only significantly increased at the highest OPO
      concentration (0.15 mg/l) on 1d and 7d, and returned to basic levels until day
      21. Hsp90 mRNA was already increased at 0.10mg/l after 1 and 7 days of exposure,
      and again was comparable to the control group on day 21. In contrast, elevated
      gst mRNA expression was only observed on day 7 at 0.10mg and 0.15 mg/l. Although
      similar trends were observed in the liver for all markers, differences were only
      significant in exceptional cases due to the high individual variation observed.
      Thus, mRNA expression in the gills rather than in the liver is recommended as a
      marker to characterize OPO-induced oxidative stress in turbot. It has to be noted
      that mRNA expression returned to basic levels on day 21 regardless the actual OPO
      concentration, suggesting a collapse of adaptive mechanisms as a possible
      explanation for the observed tissue damage.

PMID- 21899827
TI  - Glucuronidation of the steroid enantiomers ent-17beta-estradiol, ent-androsterone
      and ent-etiocholanolone by the human UDP-glucuronosyltransferases.
AB  - Steroids enantiomers are interesting compounds for detailed exploration of drug
      metabolizing enzymes, such as the UDP-glucuronosyltransferases (UGTs). We have
      now studied the glucuronidation of the enantiomers of estradiol, androsterone and
      etiocholanolone by the 19 human UGTs of subfamilies 1A, 2A and 2B. The results
      reveal that the pattern of human UGTs of subfamily 2B that glucuronidate ent
      17beta-estradiol, particularly 2B15 and 2B17, resembles the glucuronidation of
      epiestradiol (17alpha-estradiol) rather than 17beta-estradiol, the main
      physiological estrogen. The UGTs of subfamilies 1A and 2A exhibit higher degree
      of regioselectivity than enantioselectivity in the conjugation of these
      estradiols, regardless of whether the activity is primarily toward the non-chiral
      site, 3-OH (UGT1A1, UGT1A3, UGT1A7, UGT1A8 and, above all, UGT1A10), or the 17-OH
      (UGT1A4). In the cases of etiocholanolone and androsterone, glucuronidation of
      the ent-androgens, like the conjugation of the natural androgens, is mainly
      catalyzed by UGTs of subfamilies 2A and 2B. Nevertheless, the glucuronidation of
      ent-etiocholanolone and ent-androsterone by both UGT2B7 and UGT2B17 differs
      considerably from their respective activity toward the corresponding endogenous
      androgens, whereas UGT2A1-catalyzed conjugation is much less affected by the
      stereochemistry differences. Kinetic analyses reveal that the K(m) value of
      UGT2A1 for ent-estradiol is much higher than the corresponding value in the other
      two high activity enzymes, UGT1A10 and UGT2B7. Taken together, the results
      highlight large enantioselectivity differences between individual UGTs,
      particularly those of subfamily 2B.

PMID- 21899828
TI  - [Rapidly growing ulcer in a patient with neurofibromatosis type I].

PMID- 21899826
TI  - Endocrine disrupting chemicals and disease susceptibility.
AB  - Environmental chemicals have significant impacts on biological systems. Chemical
      exposures during early stages of development can disrupt normal patterns of
      development and thus dramatically alter disease susceptibility later in life.
      Endocrine disrupting chemicals (EDCs) interfere with the body's endocrine system
      and produce adverse developmental, reproductive, neurological, cardiovascular,
      metabolic and immune effects in humans. A wide range of substances, both natural
      and man-made, are thought to cause endocrine disruption, including
      pharmaceuticals, dioxin and dioxin-like compounds, polychlorinated biphenyls, DDT
      and other pesticides, and components of plastics such as bisphenol A (BPA) and
      phthalates. EDCs are found in many everyday products--including plastic bottles,
      metal food cans, detergents, flame retardants, food additives, toys, cosmetics,
      and pesticides. EDCs interfere with the synthesis, secretion, transport,
      activity, or elimination of natural hormones. This interference can block or
      mimic hormone action, causing a wide range of effects. This review focuses on the
      mechanisms and modes of action by which EDCs alter hormone signaling. It also
      includes brief overviews of select disease endpoints associated with endocrine
      disruption.

PMID- 21899829
TI  - [Risk factors for in-transit metastasis in patients with cutaneous melanoma].
AB  - BACKGROUND: In-transit metastases have been associated with the presence of
      various negative prognostic factors in patients with cutaneous melanoma. It has
      recently been suggested that sentinel lymph node biopsy (SLNB) may lead to an
      increase in the incidence of this particular type of metastasis. In this study,
      we analyzed risk factors for the appearance of in-transit metastasis and its
      potential association with the use of SLNB. MATERIAL AND METHODS: A prospective
      study was undertaken in a cohort of 404 patients with cutaneous melanoma seen in
      the melanoma unit of Hospital San Cecilio in Granada, Spain. Statistical analysis
      was performed with SPSS 15.0 and Epidat 3.1 using the chi(2) and Fisher exact
      tests. RESULTS: Out of 93 (23%) patients with recurrence at any time, 28 (6.9%)
      had in-transit metastases. The occurrence of in-transit metastasis was associated
      with age greater than 50 years, greater Breslow depth and Clark level, the
      presence of ulceration, positive SLNB, and the presence of other types of
      recurrence (local recurrence, lymph node metastasis, or distant metastasis).
      There was no relationship between surgical treatment or performing SLNB and the
      presence of in-transit metastasis. CONCLUSIONS: The risk factors for in-transit
      metastasis are the same as those for any type of recurrence and coincide with
      factors linked to poor prognosis. Given that in-transit metastases are much more
      common in patients with positive SLNB, while the technique itself is not linked
      to their occurrence, these findings suggest that the appearance of in-transit
      metastasis is linked to biological characteristics of the tumor cells rather than
      an influence of the surgical technique.

PMID- 21899830
TI  - Low-dose contrast-enhanced time-resolved MR angiography at 3T: diagnostic
      accuracy for treatment planning and follow-up of vascular malformations.
AB  - AIM: To assess the accuracy of low-dose contrast-enhanced time-resolved 3T
      magnetic resonance angiography (MRA) for the morphological and functional
      assessment of vascular malformations (VM), and to evaluate its diagnostic
      potential for the depiction of treatment-induced changes. MATERIALS AND METHODS:
      Twenty-five patients with known VM underwent MRA to evaluate the location and
      extent of lesions and their haemodynamic characteristics. Three-dimensional (3D)
      T1-weighted time-resolved sequences were acquired following the administration of
      0.05mmol/kg of gadobenate dimeglumine. VM were classified according to their
      morphology and haemodynamic characteristics. All patients thereafter underwent
      conventional angiography to confirm the diagnosis and to treat the lesions
      (embolization or sclerotherapy). Follow-up MRA was performed 30 days after
      treatment to assess morphological and functional changes. A visual analogue scale
      (VAS) was used to clinically assess the severity of symptoms before and after
      therapy. RESULTS: Based on haemodynamic characteristics, VM were classified as
      predominantly arterial [4 (16%)], artero-venous [19 (76%)] or venous [2 (8%)].
      Twenty-three (92%) lesions were classified as high-flow VM and two (8%) as low
      flow VM. Intralesional thrombosis was present in 17 (68%) lesions before therapy
      and in 10 lesions (40%) after therapy. The median VAS scores were 5+/-1 before
      treatment and 4+/-2 after treatment. Very good correlation (Spearman's
      correlation coefficient: rho=0.87; p=0.000) was noted between the reduction of
      lesion size on follow-up MRA and pain relief as assessed by VAS. CONCLUSION: Low
      dose contrast-enhanced time-resolved 3T MRA can be used to define morphological
      and functional aspects of VM accurately during treatment planning and follow-up,
      and can identify post-therapy changes that positively correlate with treatment
      outcome.

PMID- 21899831
TI  - Recovery of right and left ventricular function after acute pulmonary embolism.
AB  - AIM: To evaluate recovery of cardiac function after acute pulmonary embolism
      (PE). MATERIALS AND METHODS: Routine breath-held computed tomography (CT)
      pulmonary angiography was performed in patients with suspected PE to confirm or
      exclude the diagnosis of PE at initial presentation. Electrocardiogram (ECG)
      triggered cardiac CT was performed to assess biventricular function. After 6
      months, cardiac magnetic resonance imaging (MRI) was performed. In total, 15
      consecutive patients with PE and 10 without were studied. A significant change in
      ventricular volume was defined as a >15% change in end-diastolic or -systolic
      volumes (EDV, ESV), and significant ventricular function improvement as a >5%
      increase in ejection fraction (EF) as based on reported cut-off values. RESULTS:
      Right and left ventricular (RV and LV) EDV and ESV changed non-significantly
      (<1.3%) in the patients without PE, indicating good comparability of those values
      measured by CT and MRI. PE patients with baseline normal RV function (RVEF >=
      47%) revealed a >5% improvement in the RVEF (+5.4 +/- 3.1%) due to a decrease in
      the RVESV. Patients with baseline abnormal RV function showed a >5% improvement
      in the RVEF (+14 +/- 15%) due to decreases in both the RVESV and RVEDV.
      Furthermore, the LVEDV increased in this latter patient group. CONCLUSIONS: The
      present study demonstrated an improvement in RV function in the majority of
      patients with PE, independent of baseline RV function. The degree of RV and LV
      recovery was dependent on the severity of baseline RV dysfunction.

PMID- 21899833
TI  - Prediction of acute hypotensive episodes by means of neural network multi-models.
AB  - This work proposes the application of neural network multi-models to the
      prediction of adverse acute hypotensive episodes (AHE) occurring in intensive
      care units (ICU). A generic methodology consisting of two phases is considered.
      In the first phase, a correlation analysis between the current blood pressure
      time signal and a collection of historical blood pressure templates is carried
      out. From this procedure the most similar signals are determined and the
      respective prediction neural models, previously trained, selected. Then, in a
      second phase, the multi-model structure is employed to predict the future
      evolution of current blood pressure signal, enabling to detect the occurrence of
      an AHE. The effectiveness of the methodology was validated in the context of the
      10th PhysioNet/Computers in Cardiology Challenge-Predicting Acute Hypotensive
      Episodes, applied to a specific set of blood pressure signals, available in MIMIC
      II database. A correct prediction of 10 out of 10 AHE for event 1 and of 37 out
      of 40 AHE for event 2 was achieved, corresponding to the best results of all
      entries in the two events of the challenge. The generalization capabilities of
      the strategy was confirmed by applying it to an extended dataset of blood
      pressure signals, also collected from the MIMIC-II database. A total of 2344
      examples, selected from 311 blood pressure signals were tested, enabling to
      obtain a global sensitivity of 82.8% and a global specificity of 78.4%.

PMID- 21899834
TI  - Simulated temperature distribution of the proximal forearm.
AB  - Temperature changes in the resting proximal human forearm have been studied non
      invasively, using computer simulation. A procedure for spatial model generation,
      based on digitized slice data, has been applied. A mathematical model and a 3-D
      computer simulation program have been implemented. Heat transfer in the non
      homogenous tissue was modeled with a well known bio-heat equation. The heat
      production by tissue metabolism was modeled using the Q10 rule, while the heat
      exchange between the blood and tissue was modeled as a function of local
      temperature and regional blood flow. The stability and accuracy of the method was
      confirmed by varying the simulation parameters, the initial and boundary values,
      and the model dimensions, with subsequent analysis of the results. We have
      explained, by computer simulation, the variations in the Pennes' well-known in
      vivo measurements of the steady-state temperatures along the transverse axis of
      the proximal forearm. Suspecting that the anatomical positioning of his measuring
      probes varied, we have reconstructed their possible positions by searching for
      the simulated positions that result in the best agreement between simulated and
      measured temperature fields. Our simulations indicate that the fluctuations of
      the measured steady-state temperatures should not be smoothed out because they
      are the natural consequence of a complex interplay between the position of the
      measuring probes, anatomical position of the main arteries, dimensions of the
      forearm, blood flow, inhomogeneity of tissues, and environmental temperature.

PMID- 21899832
TI  - Numerosity and number signs in deaf Nicaraguan adults.
AB  - What abilities are entailed in being numerate? Certainly, one is the ability to
      hold the exact quantity of a set in mind, even as it changes, and even after its
      members can no longer be perceived. Is counting language necessary to track and
      reproduce exact quantities? Previous work with speakers of languages that lack
      number words involved participants only from non-numerate cultures. Deaf
      Nicaraguan adults all live in a richly numerate culture, but vary in counting
      ability, allowing us to experimentally differentiate the contribution of these
      two factors. Thirty deaf and 10 hearing participants performed 11 one-to-one
      matching and counting tasks. Results suggest that immersion in a numerate culture
      is not enough to make one fully numerate. A memorized sequence of number symbols
      is required, though even an unconventional, iconic system is sufficient.
      Additionally, we find that within a numerate culture, the ability to track
      precise quantities can be acquired in adulthood.

PMID- 21899835
TI  - [Risk of osteoporotic fracture and hip fracture in patients with chronic
      obstructive pulmonary disease].
AB  - AIM: Osteoporosis is a frequent comorbidity in patients with chronic obstructive
      pulmonary disease (COPD). We have studied the risk of major osteoporotic fracture
      and hip fracture in patients with COPD. PATIENTS AND METHODS: A multicenter cross
      sectional study was performed in Spain in 26 hospitals of 16 regional
      communities. Patients diagnosed with COPD who required admission to the Internal
      Medicine Service due to exacerbation of their respiratory disease were enrolled.
      COPD was confirmed by post-bronchodilator spirometry in stable state: maximum
      expiratory volume in the first second (FEV1) < 80% of the theoretical value and
      quotient FEV(1)/FVC < 0.70 and percent predicted after the administration of a
      bronchodilator. Dyspnea was evaluated with the modified Medical Research Council
      (mMRC) dyspnea scale. The principal variable was the likelihood of fracture
      evaluated with the FRAX(r) tool for the Spanish population. RESULTS: Three
      hundred and ninety two patients, 347 (88%) men, with a mean (SD) age of 73.7
      (8.9) years and a mean FEV1 of 1.23 liters (43.3% of predicted) were enrolled.
      Only 37 patients (9.4%), 27 men and 10 women had been diagnosed previously of
      osteoporosis. Overall, 1.8% (95% CI: 0.9-3.6) had a 10-year probability of major
      osteoporotic fracture >= 20% and 49.7% (95% CI: 44.8-54.7) had a probability of
      hip fracture >= 3%. No relationship was observed between the probability of
      fracture and GOLD stage or mMRC dyspnea scale. CONCLUSIONS: The diagnosis of
      osteoporosis is uncommon in our COPD patients. However, half of them have a high
      probability of a hip fracture in the next 10 years.

PMID- 21899836
TI  - The reliability of osteometric techniques for the sex determination of burned
      human skeletal remains.
AB  - The influence of heat-induced shrinkage on the osteometric sexual dimorphism of
      human skeletons is still poorly known. In order to investigate this issue, a
      sample composed of 84 Portuguese individuals cremated at a modern crematorium was
      examined using standard measurements from the femur, the talus and the calcaneus.
      In addition, sex determination of the sample was attempted by using osteometric
      standards developed from the Coimbra collection of identified skeletons. This was
      carried out to assess the extent of the effect of heat-induced shrinkage on the
      correct classification of known-sex skeletons while using standards developed on
      unburned skeletons. Results demonstrated that sexual dimorphism was still
      observable in the sample of calcined bones despite shrinkage. However, the
      application of conventional osteometric standards was unsuccessful. As expected,
      shrinkage caused most females to be correctly classified according to sex, but
      the sex allocation of males was very poor for all standard measurements. The
      results were obtained on a small sample but suggest that univariate metric
      techniques specifically developed for calcined bones may be valuable for sex
      determination. This would bring new methodological possibilities for biological
      anthropology and would enlarge the set of techniques regarding sex determination
      of burned skeletal remains.

PMID- 21899837
TI  - Intramedullary nailing of trochanteric fractures--operative technical tips.

PMID- 21899838
TI  - Anticoagulation management in hip fracture patients: a clinical conundrum.

PMID- 21899839
TI  - Percutaneous screw fixation for the acetabular fracture with quadrilateral plate
      involved by three-dimensional fluoroscopy navigation: surgical technique.
AB  - BACKGROUND: The percutaneous three-dimensional (3D)-fluoroscopic-navigated screw
      directing to the quadrilateral plate was attempted. MATERIALS AND METHODS: Five
      patients with acetabular fractures were treated by 3D navigated percutaneous
      screw. The quadrilateral plate was involved in all the patients. The Arcadis 3D
      (ARCADIS Orbic 3D((r)); Siemens AG Healthcare Sector, Erlangen, Germany) and
      computer navigation system (stryker navigation system) were employed, screwing
      trajectory was attempted to anchor the quadrilateral plate perpendicularly to the
      fracture line and close to the joint cartilage as much as possible. Parameters
      including fracture gap closure (P1), distance to the joint cartilage (P2),
      angulations between the screw and the fracture line (P3), were measured with the
      software installed on the machine of Arcadis 3D. RESULT: Seven screws were
      inserted with the use of 3D fluoroscopic navigation. The quadrilateral plate was
      hold by percutaneous screws. The closure of fracture gap was achieved in 3
      patients by 2-3mm. The nearest distance from the screw to the joint cartilage was
      ranged from <1mm to 6mm. The angulations between the screw and the fracture line
      was 80-90 degrees  in three patients, it was 60 degrees  and 65 degrees 
      respectively on the rest two patients. All patients felt pain free 1week after
      the operation. No complication was noted postoperatively. CONCLUSION: The
      surgical technique of percutaneous screwing for the acetabular fracture with
      three-dimensional fluoroscopy-based navigation was demonstrated.

PMID- 21899840
TI  - Mental health nurses' attitudes towards the physical health care of people with
      severe and enduring mental illness: the development of a measurement tool.
AB  - BACKGROUND: It is well established that people with schizophrenia and related
      serious mental illnesses die prematurely and have significantly higher medical co
      morbidity compared with the general population. Mental health nurses have a key
      role in improving the physical health of patients but their attitudes to this
      aspect of their role have not been systematically examined. OBJECTIVES: To
      develop and validate a measure of mental nurses' attitudes towards physical
      health care. DESIGN: The measurement tool was developed from a literature review,
      focus groups and responses to a postal questionnaire. PARTICIPANTS AND SETTING:
      All registered nursing staff working within a NHS mental health trust in the UK
      were sent the questionnaire and 585 (52%) staff responded. METHODS: Completed
      questionnaires were analysed by standard descriptive statistical methods.
      Exploratory factor analysis (principal component analysis) was used to examine
      and reduce attitude items to a coherent and parsimonious scale. RESULTS: A 28
      item measure comprised of four factors accounted for 42% of the variance. The
      factor solution appeared to provide meaningful dimensions, and the internal
      consistency of the measure and of its derived subscales was adequate (Cronbach's
      alpha between 0.76 and 0.61). The factors were labelled nurses' attitudes to
      involvement in physical health care; nurses' confidence in delivering physical
      health care; perceived barriers to physical health care delivery and nurses'
      attitudes to smoking. Validity was established by associations between the total
      scale and subscales with pre-determined respondent variables. CONCLUSION: The
      Physical Health Attitude Scale for mental health nurses (PHASe) is a first
      attempt to develop a valid and reliable measure of this important area. The
      initial development methods and its testing in a large sample provide indications
      of content and construct validity. Further testing in different samples and
      consequent refinement are necessary, however the PHASe appears to be a useful
      tool for measuring attitudes among this professional group and evaluating the
      effects of professional development.

PMID- 21899842
TI  - Early arterial abnormalities in young adulthood.

PMID- 21899841
TI  - Proteomic analysis of intra-arterial thrombus secretions reveals a negative
      association of clusterin and thrombospondin-1 with abdominal aortic aneurysm.
AB  - OBJECTIVE: Abdominal aortic aneurysm (AAA) is usually accompanied by the
      formation of a large volume of intra-luminal thrombus (ILT). ILT-derived proteins
      have been suggested as circulating markers for AAA. We conducted a proteomic
      study screening whole and hexapeptide ligand library (HLL) treated ILT explant
      secretions to identify potential ILT-derived markers for AAA. METHODS:
      Unfractionated and HLL-treated ILT secretions from 3 AAA patients were analysed
      in parallel using liquid chromatography tandem mass spectrometry (LC-MS/MS). In
      silico analyses were employed to identify proteins with biomarker potential.
      Proteomic findings were validated by measuring serum concentrations of 2
      representative ILT proteins in 313 AAA patients and 690 controls. RESULTS: A
      total of 150 proteins were identified from thrombus conditioned media; HLL
      treatment enabled the detection of 53 previously unseen polypeptides. Gene
      ontology analysis revealed high representation of platelet-secreted proteins.
      Thrombospondin-1 (TSP-1) and clusterin were selected for further assessment.
      Serum TSP-1 and clusterin were negatively associated with AAA after adjusting for
      other risk factors. Odds ratio and 95% confidence intervals were 0.62, 0.41-0.94,
      and 0.50, 0.33-0.75, for men with serum TSP-1 and clusterin in the fourth
      compared to first quartiles, respectively. CONCLUSION: This proteomic analysis
      has identified a group of proteins concentrated in AAA ILT. Assessment of
      circulating concentrations of two representative polypeptides suggests for the
      first time that the ILT selectively sequesters proteins rather than actively
      releasing them. Further work is required to assess the mechanisms underpinning
      this observation and the associated clinical implications.

PMID- 21899843
TI  - Clinically evident polyvascular disease and regression of coronary
      atherosclerosis after intensive statin therapy in patients with acute coronary
      syndrome: serial intravascular ultrasound from the Japanese assessment of
      pitavastatin and atorvastatin in acute coronary syndrome (JAPAN-ACS) trial.
AB  - AIM: To clarify whether the effects of statin treatment on plaque regression vary
      according to the presence or absence of polyvascular disease (PVD) in patients
      with acute coronary syndrome (ACS). METHODS: 307 patients with ACS who underwent
      percutaneous coronary intervention for the culprit lesion at 33 centers were
      treated with atorvastatin or pitavastatin. Noncoronary atherosclerosis was
      defined as coexistent, clinically recognized arterial disease other than coronary
      artery disease (CAD) (cerebral, aortic, or lower extremity). Intravascular
      ultrasound (IVUS) was performed to assess non-culprit coronary atherosclerosis at
      baseline and at 8-12 months follow-up. Serial IVUS examinations were obtained in
      252 patients. Atheroma volume and percent change in atheroma volume of the target
      plaque was assessed. RESULTS: Patients of the CAD+PVD (n = 19) were older (68 vs.
      62 years, p = 0.02), had lower low-density lipoprotein cholesterol (LDL-C) levels
      at baseline (116 vs. 134 mg/dL, p=0.03) than those of the CAD-only group (n =
      233), whereas LDL-C levels at follow-up were similar (81 vs. 83 mg/dL). Although
      the baseline plaque volume was similar in the two groups (59 vs. 57 mm(3)),
      patients of the CAD+PVD group showed milder regression of atherosclerosis than
      those of the CAD-only group (-8.9% vs. -18.2%, p = 0.005). This difference
      remained significant even after adjustment for coronary risk factors including
      age and serum LDL-C (p = 0.047). CONCLUSIONS: Statin treatment results in milder
      regression of coronary atherosclerosis in CAD patients with polyvascular disease
      compared to those with CAD only.

PMID- 21899844
TI  - Limits of recovery against slip-induced falls while walking.
AB  - Slip-induced falls in gait often have devastating consequences. The purposes of
      this study were 1) to select the determinants that can best discriminate the
      outcomes (recoveries or falls) of an unannounced slip induced in gait (and to
      find their corresponding threshold, i.e., the limits of recovery, which can
      clearly separate these two outcomes), and 2) to verify these results in a subset
      of repeated-slip trials. Based on the data collected from 69 young subjects
      during a slip induced in gait, nine different ways of combining the center of
      mass (COM) stability, the hip height, and its vertical velocity were investigated
      with the aid of logistic regression. The results revealed that the COM stability
      (s) and limb support (represented by the quotient of hip vertical velocity to hip
      height, S(hip)) recorded at the instant immediately prior to the recovery step
      touchdown were sufficiently sensitive to account for all (100%) variance in
      falls, and specific enough to account for nearly all (98.3%) variability in
      recoveries. This boundary (S(hip)=-0.22s-0.25), which quantifies the risk of
      falls in the stability-limb support quotient (s-S(hip)) domain, was fully
      verified using second-slip and third-slip trials (n=76) with classification of
      falls at 100% and recoveries at 98.6%. The severity of an actual fall is likely
      to be greater further below the boundary, while the likelihood of a fall
      diminishes above it. Finally, the slope of the boundary also indicates the
      tradeoff between the stability and limb support, whereby high stability can
      compensate for the insufficiency in limb support, or vice versa.

PMID- 21899845
TI  - The effects of pad geometry and material properties on the biomechanical
      effectiveness of 26 commercially available hip protectors.
AB  - Wearable hip protectors (padded garments) represent a promising strategy to
      decrease impact force and hip fracture risk during falls, and a wide range of
      products are currently marketed. However, little is known about how design
      features of hip protectors influence biomechanical effectiveness. We used a
      mechanical test system (simulating sideways falls) to measure the attenuation in
      femoral neck force provided by 26 commercially available hip protectors at three
      impact velocities (2, 3, and 4m/s). We also used a materials testing machine to
      characterize the force-deflection properties of each device. Regression analyses
      were performed to determine which geometric (e.g., height, width, thickness,
      volume) and force-deflection properties were associated with force attenuation.
      At an impact velocity of 3m/s, the force attenuation provided by the various hip
      protectors ranged between 2.5% and 40%. Hip protectors with lower stiffness
      (measured at 500N) provided greater force attenuation at all velocities.
      Protectors that absorbed more energy demonstrated greater force attenuation at
      the higher impact velocities (3 and 4m/s conditions), while protectors that did
      not directly contact (but instead bridged) the skin overlying the greater
      trochanter attenuated more force at velocities of 2 and 3m/s. At these lower
      velocities, the force attenuation provided by protectors that contacted the skin
      overlying the greater trochanter increased with increasing pad width, thickness,
      and energy dissipation. By providing a comparison of the protective value of a
      large range of existing hip protectors, these results can help to guide consumers
      and researchers in selecting hip protectors, and in interpreting the results of
      previous clinical trials. Furthermore, by determining geometric and material
      parameters that influence biomechanical performance, our results should assist
      manufacturers in designing devices that offer improved performance and clinical
      effectiveness.

PMID- 21899846
TI  - Pressure oscillation delivery to the lung: Computer simulation of neonatal
      breathing parameters.
AB  - Preterm newborn infants may develop respiratory distress syndrome (RDS) due to
      functional and structural immaturity. A lack of surfactant promotes collapse of
      alveolar regions and airways such that newborns with RDS are subject to increased
      inspiratory effort and non-homogeneous ventilation. Pressure oscillation has been
      incorporated into one form of RDS treatment; however, how far it reaches various
      parts of the lung is still questionable. Since in-vivo measurement is very
      difficult if not impossible, mathematical modeling may be used as one way of
      assessment. Whereas many models of the respiratory system have been developed for
      adults, the neonatal lung remains essentially ill-described in mathematical
      models. A mathematical model is developed, which represents the first few
      generations of the tracheo-bronchial tree and the 5 lobes that make up the
      premature ovine lung. The elements of the model are derived using the lumped
      parameter approach and formulated in SimulinkTM within the MatlabTM environment.
      The respiratory parameters at the airway opening compare well with those measured
      from experiments. The model demonstrates the ability to predict pressures, flows
      and volumes in the alveolar regions of a premature ovine lung.

PMID- 21899847
TI  - The mechanics of the primary cilium: an intricate structure with complex
      function.
AB  - The primary cilium is a non-motile singular cellular structure that extends from
      the surface of nearly every cell in the body. The cilium has been shown to play
      numerous roles in maintaining tissue homeostasis, through regulating signaling
      pathways and sensing both biophysical and biochemical changes in the
      extracellular environment. The structural performance of the cilium is paramount
      to its function as defective cilia have been linked to numerous pathologies. In
      particular, the cilium has demonstrated a mechanosensory role in tissues such as
      the kidney, liver, endothelium and bone, where cilium deflection under mechanical
      loading triggers a cellular response. Understanding of how cilium structure and
      subsequent mechanical behavior contributes to the roles that cilium plays in
      regulating cellular behavior is a compelling question, yet is a relatively
      untouched research area. Recent advances in biophysical measurements have
      demonstrated the cilium to be a structurally intricate organelle containing an
      array of load bearing proteins. Furthermore advances in modeling of this
      organelle have revealed the importance of these proteins at regulating the
      cilium's mechanosensitivity. Remarkably, the cilium is capable of adapting its
      mechanical state, altering its length and possibly it's bending resistance, to
      regulate its mechanosensitivity demonstrating the importance of cilium mechanics
      in cellular responses. In this review, we introduce the cilium as a
      mechanosensor; discuss the advances in the mechanical modeling of cilia; explore
      the structural features of the cilium, which contribute to its mechanics and
      finish with possible mechanisms in which alteration in structure may affect
      ciliary mechanics, consequently affecting ciliary based mechanosensing.

PMID- 21899848
TI  - Advances in food analysis.

PMID- 21899849
TI  - Electromembrane extraction of stimulating drugs from undiluted whole blood.
AB  - For the first time, electromembrane extraction (EME) of six basic drugs of abuse
      from undiluted whole blood and post mortem blood in a totally stagnant system is
      reported. Cathinone, methamphetamine, 3,4-methylenedioxy-amphetamine (MDA), 3,4
      methylenedioxy-methamphet-amine (MDMA), ketamine and 2,5-dimethoxy-4
      iodoamphetamine (DOI) were extracted from the whole blood sample, through a
      supported liquid membrane (SLM) consisting of 1-ethyl-2-nitrobenzene (ENB)
      immobilized in the pores of a hollow fiber, and into an aqueous acceptor solution
      inside the lumen of the hollow fiber. The SLM acts as a barrier with efficient
      exclusion of all macromolecules and acidic substances in the sample. Due to the
      application of the electrical field, only the cationic compounds of interest are
      extracted efficiently across the membrane, thus providing extremely clean
      extracts for analysis with liquid chromatography-mass spectrometry, LC-MS.
      Recoveries in the range 10-30% were obtained from 80 MUl whole blood within 5 min
      extraction time and an applied voltage of 15V across the SLM. The optimized
      technique was tested on real forensic whole blood samples taken from three
      forensic autopsy cases and on five forensic whole blood samples from living
      persons. The results were in agreement with the analysis using standard sample
      preparation methods (liquid-liquid extraction) performed on the same samples by
      Norwegian Institute of Public Health (NIPH), Division of Forensic Toxicology and
      Drug Abuse Research. Evaluation data were acceptable, with limit of detections
      (LODs) in the range 40-2610 pg/mL, well below concentrations associated with drug
      abuse; linearites in the range between 10 and 250 ng/mL with r(2) values above
      0.9939, and with repeatability (RSD) of 7-32%.

PMID- 21899851
TI  - Comprehensive analysis of mate (Ilex paraguariensis) compounds: development of
      chemical strategies for matesaponin analysis by mass spectrometry.
AB  - Ilex paraguariensis (mate) is an important plant from southern Brazil, Paraguay,
      Uruguay and Argentina, where its leaves are widely used in hot or cold beverages.
      We now present a comprehensive ULPC-PDA-MS analysis of the compounds found in its
      leaves. The analysis was rapid, less than 13 min and many compounds were
      identified, among these, the chlorogenic acid series, and other quinic acid
      derivatives, xanthines, and several saponins, many of which have not been
      previously described, including many isomers. The isomerism could occur in the
      aglycone moiety, namely ursolic or oleanolic acid, or in the carbohydrate moiety.
      Additionally, many acetylated saponins were detected. The structure of known and
      novel saponins was determined using per-O-methylation with ESI-MS analysis, as
      well as with GC-MS of their partially O-methylated alditol acetate (PMAA)
      derivatives, along with ESI-MS analysis of the O-isopropylidene (IPP) derivatives
      provided fundamental information on interglycosidic linkages, avoiding the
      purification steps.

PMID- 21899850
TI  - Morphological modification of nanostructured ultrathin-layer chromatography
      stationary phases.
AB  - Ultrathin-layer chromatography (UTLC) provides the high sensitivities and rapid
      separations over short distances desirable in many analytical applications. The
      dependence of these performance benefits on UTLC layer microstructure motivates
      continued stationary phase engineering efforts. A new method of modifying the
      elution behaviours of nanostructured thin film UTLC stationary phases is
      investigated in this report. Macroporous normal phase silica thin films ~5 MUm
      thick were fabricated using glancing angle deposition (GLAD). Reactive ion
      etching (RIE) and a subsequent annealing treatment modified stationary phase
      morphology to tune migration velocity, analyte retention, and overall separation
      performance. Combining this technique with a RIE shadow mask enabled fabrication
      of adjacent concentration and separation zones with markedly different elution
      properties. Although produced using an entirely new approach, GLAD UTLC
      concentration zone media behaved in a manner consistent with traditional thin
      layer chromatography (TLC) and high-performance TLC (HPTLC) concentration zone
      plates. In particular, these new media focused large volume, low concentration
      dye mixture spots into narrow bands to achieve high-quality separations. The
      described approach to modifying the morphology and resultant elution behaviours
      of nanostructured stationary phases expands the capabilities of the GLAD UTLC
      technique.

PMID- 21899852
TI  - Coupling frontal elution paper chromatography with desorption corona beam
      ionization mass spectrometry for rapid analysis of chlorphenamine in herbal
      medicines and dietary supplements.
AB  - We developed a convenient method by coupling frontal elution paper chromatography
      with desorption corona beam ionization mass spectrometry (DCBI-MS) for rapid
      determination of chlorphenamine added in herbal medicines or dietary supplements.
      In this method, the ethanol extract of the herbal products was spotted directly
      onto an isosceles triangular filter paper sheet, and then the paper sheet was
      developed under strong elution condition with the sample zone migrating at the
      solvent front. The analyte was finally condensed at the V-shaped tip which could
      then be placed under the visible plasma beam of DCBI for ionization. The overall
      procedure took less than 5 min. The frontal elution paper chromatography on a
      triangular plate used in this work improved the signal intensity of
      chlorphenamine by 30-fold due to the analyte condensing at the tip and the
      reduction of the background suppression. Furthermore, the paper sheet also
      functioned as a filter in the analysis of solid or powder samples, which can
      increase the analytical throughput by omitting the step of centrifugation. The
      proposed method in current study was successfully applied in the determination of
      chlorphenamine in herbal medicines. Chlorphenamine was detected in four of the
      twelve types of herbal medicines examined in this study. The limit of detection
      was 200 ng/mL (2.0 ng absolute) in full-scan positive-ion mode and the linear
      range was from 5.0 MUg/mL to 50 MUg/mL with satisfactory linear coefficient (R(2)
      (the square of the correlation coefficient)=0.895). Good reproducibility was
      achieved with relative standard deviations (RSDs) less than 15.0% and the
      recoveries of chlorphenamine ranged from 84.3 to 90.6%.

PMID- 21899853
TI  - Development of a liquid chromatography tandem mass spectrometry method for
      simultaneous determination of eight adulterants in slimming functional foods.
AB  - A method for simultaneous determination of eight adulterants including two
      appetite suppressants, two energy expenditure-enhancing drugs, one diuretic and
      three cathartics in slimming functional foods by high performance liquid
      chromatography with electrospray ionization-tandem mass spectrometry (HPLC-ESI
      MS/MS) was established. After samples were ultrasonically extracted with 70%
      (v/v) methanol aqueous solution and centrifuged, the components of ephedrine,
      norpseudoephedrine, fenfluramine, sibutramine, clopamide, emodin, rhein, and
      chrysophanol in sample solution were separated by a Hypersil Gold column (2.1 mm
      * 150 mm, 5 MUm) using a programmed gradient elution. A mobile phase consisting
      of 0.02% (v/v) formic acid-ammonium formate buffer solution (pH=3.50) and
      methanol was used for elution with a flow rate set at 250 MUL/min and column
      temperature of 25  degrees C. Qualitative determination was based on
      characteristic ion pairs and retention time of the targeted compounds using SRM
      (selective reaction monitoring) mode. Clenbuterol and ibuprofen were internal
      standards in positive and negative ionization mode, respectively. The internal
      standard curves were used for quantification measurement. The average recoveries
      of three different concentrations were from 80.2% to 94.5%. The limits of
      detection (LODs) were from 0.03 to 0.66 mg/kg (except chrysophanol 1.6 mg/kg).
      The linear dynamic range covered from 1 to 500 MUg/L (except chrysophanol 50-5000
      MUg/L) for the twelve samples analyzed. Adulterants in four different kinds of
      slimming functional foods were determined by this developed method, and
      satisfactory results were obtained. These experimental results showed that,
      adulteration of sibutramine or/and fenfluramine were the major adulterating
      components with contents varying from 6.1 to 1.3*10(3) mg/kg and 1.9 to 9.7*10(3)
      mg/kg, respectively. In addition, three cathartic compounds were detected in six
      of those tested samples, and ephedrine, norpseudoephedrine and clopamide were not
      detected in all samples.

PMID- 21899854
TI  - Application of QuEChERS method for extraction of selected persistent organic
      pollutants in fish tissue and analysis by gas chromatography mass spectrometry.
AB  - The QuEChERS method developed for 22 organochlorine pesticides (OCPs) and 7
      polychlorinated biphenyls (PCBs) in fish tissue involves a simple and efficient
      freezing technique for removal of lipids. The equipment developed consists of
      disposable syringes and a freezing block constructed from simple materials found
      in most laboratories. The freezing block keeps the temperature in the extract at 
      20.5 degrees C up to 10 min after being exposed to room temperature. After the
      freezing step 69% of the lipids in tilapia and 61% in salmon are removed. Further
      reduction of co-extractives up to 96% in tilapia and 87% in salmon can be made by
      treatment with CaCl(2) and primary secondary amino sorbent (PSA) which removes
      the fatty acids. Spiking experiments in tilapia at 5 and 50 ng/g and extracted
      with acetonitrile show recovery range from 70 to 115% for all compounds. In
      salmon the recoveries are in the range 43-118% for the OCPs and 26-65% for the
      PCBs. Analysis of a standard reference material shows acceptable results for most
      of the pesticides but low results for the PCBs. The estimated LOQs were in the
      range 1-5 ng/g for tilapia and 2-10 ng/g for salmon. The method has been applied
      to analyse fish samples from Lake Koka in Ethiopia. It was investigated if
      addition of a less polar water miscible solvent than acetonitrile could increase
      the recovery of OCPs and PCBs. The results show that a mixture of 75%
      acetonitrile and 25% tetrahydrofurane (ACN/THF 75/25) clearly enhances the
      recoveries for most OCPs (47-101%) and PCBs (42-79%) from salmon. The recovery of
      aldrin increases significantly from 55% to over 80%. The method using ACN/THF
      75/25 is applicable to the extraction of OCPs and PCBs from fish tissue having a
      lipid content of up to about 11% (salmon) with recoveries >=70% for most of the
      OCPs and >=42% for the PCBs.

PMID- 21899855
TI  - Development of an on-column enrichment technique based on C18-functionalized
      magnetic silica nanoparticles for the determination of lidocaine in rat plasma by
      high performance liquid chromatography.
AB  - In this study, a novel on-column enrichment technique filled with C(18)
      functionalized magnetic silica nanoparticles was successfully developed for the
      determination of lidocaine in rat plasma by high performance liquid
      chromatography (HPLC). The synthesized Fe(3)O(4)@SiO(2)-C(18) nanoparticles were
      locally packed into the capillary by the application of magnets. Lidocaine in the
      sample solutions pumped into the capillary tube could be easily adsorbed by
      Fe(3)O(4)@SiO(2)-C(18) through hydrophobic interaction by the interior C(18)
      groups, and eluted by acetonitrile solution. Different extraction conditions were
      investigated. Method validations including linear range, quantification limit,
      detection limit, precision, accuracy and recovery were also studied. The results
      showed that the proposed method based on on-column enrichment by Fe(3)O(4)@SiO(2)
      C(18) was a novel, little solvent and efficient approach for the determination of
      lidocaine in the complex plasma samples.

PMID- 21899856
TI  - High efficiency, high temperature separations on silica based monolithic columns.
AB  - The effect of temperature on separation using reversed-phase monolithic columns
      has been investigated using a nano-LC pumping system for gradient separation of
      tryptic peptides with MS detection. A goal of this study was to find optimal
      conditions for high-speed separations. The chromatographic performance of the
      columns was evaluated by peak capacity and peak capacity per time unit. Column
      lengths ranging from 20 to 100 cm and intermediate gradient times from 10 to 30
      min were investigated to assess the potential of these columns in a final step
      separation, e.g. after fractionation or specific sample preparation. Flow rates
      from 250 to 2000 nL/min and temperatures from 20 to 120 degrees C were
      investigated. Temperature had a significant effect on fast separations, and a
      flow rate of 2000 nL/min and a temperature of 80 degrees C gave the highest peak
      capacity per time unit. These settings produced 70% more protein identifications
      in a biological sample compared to a conventional packed column. Alternatively,
      an equal amount of protein identifications was obtained with a 40% reduction in
      run time compared to the conventional packed column.

PMID- 21899858
TI  - The value of immunohistochemical expression of BAX in formulating a prognosis for
      canine cutaneous mast cell tumours.
AB  - Immunohistochemical expression of BAX was evaluated in 24 canine cutaneous mast
      cell tumours in order to verify the relationship of this expression to the
      histopathological grade of the lesions and its prognostic value for clinical
      outcome. BAX expression increased with higher histopathological grades (P=0.0148;
      P<0.05 between grades I and III). Animals with high levels of BAX expression were
      4.25 times more likely to die from the disease and had shorter post-surgical
      survival times (P=0.0009). These results suggest that alterations in BAX
      expression may be related to the aggressiveness of canine cutaneous mast cell
      tumours, indicating that immunohistochemical detection of BAX may be predictive
      of clinical outcome.

PMID- 21899857
TI  - Dual infection of fetal and neonatal small ruminants with border disease virus
      and peste des petits ruminants virus (PPRV): neuronal tropism of PPRV as a novel
      finding.
AB  - Dual infection of 26 fetal and neonatal small ruminants with border disease virus
      (BDV) and peste des petits ruminants virus (PPRV) is reported. The animals
      included five aborted lamb fetuses, 19 neonatal lambs and two neonatal kids from
      flocks in regions of the Black Sea and the Aegean region. BDV and PPRV antigens
      were detected immunohistochemically in the brain, oral mucosa, intestine and lung
      of infected animals. Reverse transcriptase-polymerase chain reaction was used to
      demonstrate PPRV and BDV in samples of the spleen, lymph node, lung and brain
      from infected animals. On the basis of observations made, it is concluded that
      brain damage following intrauterine infection with BDV facilitates the passage of
      PPRV to the brain and results in infection of neuronal and glial cells by PPRV.

PMID- 21899859
TI  - Carotid body remodelling in l-NAME-induced hypertension in the rat.
AB  - The carotid body (CB) is a chemoreceptor organ located at the bifurcation of the
      common carotid artery. It is made up of the carotid glomus, a structure
      containing type 1 cells surrounded by type 2 cells. The aim of this study was to
      evaluate the morphological changes of the CB and carotid glomus in the rat model
      of l-NAME-induced hypertension. Male Wistar rats were divided in two groups:
      control untreated rats (C) and rats receiving l-NAME 40 mg/kg/day (LN) for 6
      weeks. At the end of the experiment, the systolic blood pressure was 63% higher
      in the LN group compared with the C group. Morphometric analysis showed that the
      area of the CB was 29% greater in the LN group compared with the C group. The
      density of nuclei in the CB was similar between groups, but it was 31% less in
      the carotid glomus of the LN group. Cells in the CB of the LN group displayed
      cytoplasmic vacuolation and expressed several biogenic amines. There were more
      elastic fibres, proteoglycans and collagen fibres in the LN group compared with
      the C group. Immunohistochemistry showed increased expression of nuclear factor
      kB, substance P, vascular endothelial growth factor and neuronal nitric oxide
      synthase in the LN group, while expression of the protein gene product 9.5 was
      decreased. l-NAME alters cell morphology and the expression of extracellular
      matrix molecules in the CB and carotid glomus in rats with l-NAME-induced
      hypertension.

PMID- 21899860
TI  - The power of well-connected arguments: early sensitivity to the connective
      because.
AB  - Connectives, such as because, are routinely used by parents when addressing their
      children, yet we do not know to what extent children are sensitive to their use.
      Given children's early developing abilities to evaluate testimony and produce
      arguments containing connectives, it was hypothesized that young children would
      show an appropriate reaction to the presence of connectives. Three experiments
      were conducted to test this hypothesis. In each, two informants gave
      contradicting statements regarding the location of an object and justified their
      positions by using a similar argument. Only one of the informants used the
      connective because to link his argument to the statement. In each experiment, the
      3-year-olds performed at chance in selecting choices containing the connective
      because, but the 4- and 5-year-olds performed above chance. Moreover, in
      Experiments 2 and 3, the 4-year-olds, 5-year-olds, and adults performed
      significantly better than the 3-year-olds. These findings show that 4-year-olds,
      5-year-olds, and adults are sensitive to the presence of connectives. An
      interpretation of the difference in performance between the 3-year-olds and the 4
      and 5-year-olds in terms of metarepresentational skills is suggested.

PMID- 21899862
TI  - [Orbital subperiotal hematoma associated with extradural hematoma: one case
      report].
AB  - Subperiotal hematoma of the orbit associated with extradural hematoma has been
      rarely reported in the literature. We report a case of an 8-year-old girl who
      presented after traumatism, a subperiotal hematoma of the orbit with two
      extradural hematomas. During the first clinical examination realized while the
      patient was unconscious, left exophthalmia was found, but after conscious
      improvement, we discovered ophtalmoplegia and a grade I papilla edema. The CT
      scan showed two extradural hematomas and a left intraorbital hematoma. The
      intraorbital hematoma was drained by surgical way but the extradural hematomas
      were not surgical. The outcome has been marked by the neurological improvement
      and the oculomotricity recovering.

PMID- 21899863
TI  - [Nasal dermoid cyst with intracranial extension: which approach?].
AB  - Dermoid cyst is the most common midline congenital nasal tumor. Intracranial
      extension is rare but possible, must be suspected and confirmed by a cerebral
      magnetic resonance imagining (MRI). Only total surgical removal via a combined
      intracranial/extracranial approach appears to provide a complete resolution and
      effective protection against late recurrence. We report a case of a 2 years old
      patient who was operated for a nasal congenital cyst extending to the nasal
      septum. Anatomopathology showed a dermoid cyst. Five years later, he presented
      local recurrence of the dermoid cyst with intracranial extension through a bifid
      crista galli. We conclude that to avoid recurrence, the removal of the nasal cyst
      and sinus tract must be followed to its dural attachment. A transfacial approach
      can be associated with frontal craniotomy, which can provide adequate exposure
      for complete removal of the intracranial component of the cyst and sinus tract. A
      literature review was performed.

PMID- 21899864
TI  - Isolation, identification and quantitation of hydroxycinnamic acid conjugates,
      potential platform chemicals, in the leaves and stems of Miscanthus * giganteus
      using LC-ESI-MSn.
AB  - Miscanthus*giganteus is a source of platform chemicals and bioethanol through
      fermentation. Cinnamates in leaves and stems were analysed by LC-ESI-MS(n). Free
      phenols were extracted and separated chromatographically. More than 20
      hydroxycinnamates were identified by UV and LC-ESI-MS(n). Comparative LC-MS
      studies on the leaf extract showed isomers of O-caffeoylquinic acid (3-CQA, 4-CQA
      and 5-CQA), O-feruloylquinic acid (3-FQA, 4-FQA and 5-FQA) and para
      coumaroylquinic acid (3-pCoQA and 5-pCoQA). Excepting 3-pCoQA, all were also
      detected in stem. 5-CQA dominated in leaf; a mandelonitrile-caffeoylquinic acid
      dominated in stem. Three minor leaf components were distinguished by
      fragmentation patterns in a targetted MS(2) experiment as dicaffeoylquinic acid
      isomers. Others (M(r) 516) were tentatively identified as hexosylcaffeoyl
      quinates. Three positional isomers of O-caffeoylshikimic acid were minor
      components. p-Hydroxybenzaldehyde was also a major component in stem. This is the
      first report of the hydroxycinnamic acid profile of leaves and stems of
      M.*giganteus.

PMID- 21899865
TI  - Triterpenes and a triterpene glucoside from Dysoxylum cumingianum.
AB  - Six triterpenes and a triterpene glucoside were isolated from the MeOH extract of
      the leaves of Dysoxylum cumingianum together with three known triterpenes. Their
      structures were elucidated by extensive spectroscopic analyses. In cytotoxicity
      assays against three human cancer cell lines, including a multi-drug resistant
      cancer cell line (KB-C2), compounds 1, 2 and 5 demonstrated significantly
      enhanced cytotoxicity against KB-C2 cells in the presence of 2.5 MUM colchicine,
      as compared with those in the absence of colchicine. This result suggested that
      these triterpenes might show some MDR-reversing effects.

PMID- 21899866
TI  - Neurotoxicity of the CNS: diagnosis, treatment and prevention.
AB  - Treatment-induced CNS toxicity remains a major cause of morbidity in patients
      with cancer. Real advances in the design of safer radiation procedures have been
      counterbalanced by a wider use of combined radiotherapy (RT)-chemotherapy
      regimens, the development of radiosurgery, and the increasing number of long-term
      survivors. While classic radionecrosis or chemonecrosis have become less common,
      more subtle changes such as progressive cognitive dysfunction are increasingly
      reported after RT (radiation-induced leukoencephalopathy) or chemotherapy
      (administered alone or in combination). The most important and controversial
      complications of RT, chemotherapy and combined treatments in the CNS are reviewed
      here, including new diagnostic tools, practical management and prevention that
      will influence the future management of cancer patients.

PMID- 21899867
TI  - Viscoelastic clot strength predicts coagulation-related mortality within 15
      minutes.
AB  - BACKGROUND: Predicting refractory coagulopathy early in resuscitation of injured
      patients may decrease a leading cause of preventable death. We hypothesized that
      clot strength (G) measured by point-of-care rapid thrombelastography (r-TEG) on
      arrival in the emergency department can predict massive transfusion (MT) and
      coagulation-related mortality (MT-death). METHODS: Trauma alerts/activations from
      May 2008 to September 2010 were reviewed. The variables included the following:
      age, sex, injury severity score (ISS), systolic blood pressure (SBP), base
      deficit (BD), traditional coagulation tests (international normalized ratio
      ([INR], partial thromboplastin time [PTT]), TEG-derived G, and blood products
      transfused within the first 6 hours. Independent predictors of 2 outcomes (MT
      [>=10 packed red blood cells units/6 h] and MT-related death) were identified
      using logistic regression. The individual predictive values of BD, INR, PTT, and
      G were assessed comparing the areas under the receiver operating characteristic
      curves (AUC ROC), while adjusting for age, ISS, and SBP. RESULTS: Among the 80
      study patients, 48% required MT, and 21% died of MT-related complications. INR,
      ISS, and G were independent predictors of MT, whereas age, ISS, SBP, and G were
      independently associated with MT-death. The predictive power for outcome MT did
      not differ among INR (adjusted AUC ROC = 0.92), PTT (AUC ROC = 0.90, P = .41), or
      G (AUC ROC = 0.89, P = .39). For outcome MT-death, G had the greatest adjusted
      AUC ROC (0.93) compared with the AUC ROC for BD (0.87, P = .05), INR (0.88, P =
      .11), and PTT (0.89; P = .19). CONCLUSION: These data suggest that the point-of
      care TEG parameter clot strength (G) provides consistent, independent prediction
      of MT and MT-death early in the resuscitation of injured patients.

PMID- 21899870
TI  - Transverse (lateral) instantaneous force of an acoustical first-order Bessel
      vortex beam centered on a rigid sphere.
AB  - In a recent report [F.G. Mitri, Z.E.A. Fellah, Ultrasonics 51 (2011) 719-724], it
      has been found that the instantaneous axial force (i.e. acting along the axis of
      wave propagation) of a Bessel acoustic beam centered on a sphere is only
      determined for the fundamental order (i.e. m=0) but vanishes when the beam is of
      vortex type (i.e. m>0, where m is the order (or helicity) of the beam). It has
      also been recognized that for circularly symmetric beams (such as Bessel beams of
      integer order), the transverse (lateral) instantaneous force should vanish as
      required by symmetry. Nevertheless, in this commentary, the present analysis
      unexpectedly reveals the existence of a transverse instantaneous force on a rigid
      sphere centered on the axis of a Bessel vortex beam of unit magnitude order (i.e.
      |m|=1) not reported in [F.G. Mitri, Z.E.A. Fellah, Ultrasonics 51 (2011) 719
      724]. The presence of the transverse instantaneous force components of a first
      order Bessel vortex beam results from mathematical anti-symmetry in the surface
      integrals, but vanishes for the fundamental (m=0) and higher-order Bessel
      (vortex) beams (i.e. |m|>1). Here, closed-form solutions for the instantaneous
      force components are obtained and examples for the transverse components for
      progressive waves are computed for a fixed and a movable rigid sphere. The
      results show that only the dipole (n=1) mode in the scattering contributes to the
      instantaneous force components, as well as how the transverse instantaneous force
      per unit cross-sectional surface varies versus the dimensionless frequency ka (k
      is the wave number in the fluid medium and a is the sphere's radius), and the
      half-cone angle beta of the beam. Moreover, the velocity of the movable sphere is
      evaluated based on the concept of mechanical impedance. The proposed analysis may
      be of interest in the analysis of transverse instantaneous forces on spherical
      particles for particle manipulation and rotation in drug delivery and other
      biomedical or industrial applications.

PMID- 21899869
TI  - In vivo differentiation of adipose-derived stem cells in an injectable poloxamer
      octapeptide hybrid hydrogel.
AB  - A hybrid hydrogel (PP) composed of Polomaxer-407 (PO) and octapeptide with amino
      acid sequence of KFEFKFEF (PE) was prepared to make a scaffold material
      incorporating PO's high and tunable mechanical strength and integrity with PE's
      superior bioactivity. Human adipose-derived mesenchymal stem cells (hASCs) were
      encapsulated into PE, PO and PP hydrogels respectively and injected
      subcutaneously at the dorsal neck area of nude mice. Adipose-like tissue
      regeneration was only observed in the mice injected with cell-encapsulated PP
      hydrogel. No adipose regeneration was found in the mice injected with PO or PE.
      Immunohistochemistry analysis with mouse anti-human nuclei monoclonal antibody
      demonstrated that the cells in the regenerated adipose-like tissue was originated
      from the injected hASCs. The growth of blood capillaries indicated that the
      regenerated adipose-like tissue was living tissue. In addition, human-originated
      cells were also found in nude mice skin. These cells were positive with mouse
      anti-human cells keratin antibody, suggesting that the injected hASCs migrated to
      the skin and differentiated into epithelial cells in vivo.

PMID- 21899868
TI  - Morphologic changes and prognosis of the respiratory tract epithelium in
      inhalation injury and their relationship with clinical manifestations.
AB  - BACKGROUND: We set out to observe the morphologic changes and determine prognosis
      based on airway epithelial injury after inhalation injury of varying severity
      using a fiberbronchoscope and to explore the relationship between the severity of
      epithelial injury and its clinical manifestation. METHODS: Sixty burn patients
      with an inhalation injury underwent fiberoptic bronchoscopy. Morphologic changes
      of the airway epithelium were observed, and the inhalation injury was divided
      into 3 categories based on the severity of the epithelial injury: first-degree
      injury, in which the airway epithelium had slight hyperemia and edema; second
      degree injury, in which obvious epithelial hyperemia and edema, epithelial
      erosion, or petechial hemorrhage was observes; and third-degree, in which the
      airway epithelium had necrosis and exfoliation. For all groups, chest radiographs
      were examined. The duration of ventilation was recorded. RESULTS: Among 60
      patients, 16 (27%) had first-degree injury, 33 (55%) had second-degree injury,
      and 11 (18%) had third-degree injury. Among this last group, 4 patients with
      epithelial exfoliation had airway hemorrhage. In this study, 38 of 60 (63%)
      patients presented with abnormal findings on lung radiographs and 9 of 60 (15%)
      developed pulmonary infections. The duration of ventilation averaged 2 days for
      second-degree injury and 14 days for third-degree injury. The recovery times for
      first-, second-, and third-degree injury were 7, 16, and 29 days, respectively.
      CONCLUSION: Fiberoptic bronchoscopy contributes to the accurate evaluation of
      tracheal epithelial injury severity. As the severity of inhalation injury
      increased, the clinical symptoms also increased. Severe complications (eg,
      bleeding and asphyxia caused by epithelial slough) may occur in patients with
      third-degree injury and should be closely observed by clinicians. The airway
      epithelium has a substantial potential for repair. Even if the airway epithelial
      injury is severe, the damaged epithelium will recover.

PMID- 21899871
TI  - Analysis of 2-D motion tracking in ultrasound with dual transducers.
AB  - We study displacement and strain measurement error of dual transducers (two
      linear arrays, aligned orthogonally and coplanar). Displacements along the beam
      of each transducer are used to obtain measurements in two-dimensions. Simulations
      (5MHz) and experiments (10MHz) are compared to measurements with a single linear
      array, with and without angular compounding. Translation simulations demonstrate
      factors of 1.07 larger and 8.0 smaller biases in the axial and lateral directions
      respectively, for dual transducers compared to angular compounding. As the angle
      between dual transducers decreases from 90 degrees  to 40 degrees , for 1%
      compression simulations, the lateral RMS error ranges from 2.1 to 3.9MUm compared
      to 9MUm with angular compounding. Simulation of dual transducer misalignment of
      1mm and 2 degrees  result in errors of less than 9MUm. Experiments demonstrate
      factors of 3.0 and 5.2 lower biases for dual transducers in the axial and lateral
      directions respectively compared to angular compounding.

PMID- 21899872
TI  - Morphological architecture of dual-layer hollow fiber for membrane distillation
      with higher desalination performance.
AB  - A new strategy to enhance the desalination performance of polyvinylidene fluoride
      (PVDF) hollow fiber membrane for membrane distillation (MD) via architecture of
      morphological characteristics is explored in this study. It is proposed that a
      dual-layer hollow fiber consisting of a fully finger-like macrovoid inner-layer
      and a sponge-like outer-layer may effectively enhance the permeation flux while
      maintaining the wetting resistance. Dual-layer fibers with the proposed
      morphology have been fabricated by the dry-jet wet spinning process via careful
      choice of dopes composition and coagulation conditions. In addition to high
      energy efficiency (EE) of 94%, a superior flux of 98.6 L m(-2) h(-1) is obtained
      during the direct contact membrane distillation (DCMD) desalination experiments.
      Moreover, the liquid entry pressure (LEP) and long-term DCMD performance test
      show high wetting resistance and long-term stability. Mathematical modeling has
      been conducted to investigate the membrane mass transfer properties in terms of
      temperature profile and apparent diffusivity of the membranes. It is concluded
      that the enhancement in permeation flux arises from the coupling effect of two
      mechanisms; namely, a higher driving force and a lower mass transfer resistance,
      while the later is the major contribution. This work provides an insight on MD
      fundamentals and strategy to tailor making ideal membranes for DCMD application
      in desalination industry.

PMID- 21899873
TI  - Role of histidine 225 in adenosylcobalamin-dependent ornithine 4,5-aminomutase.
AB  - Pyridoxal 5'-phosphate (PLP), in the active site of ornithine 4,5-aminomutase
      (OAM), forms a Schiff base with N(delta) of the d-ornithine side chain and
      facilitates interconversion of the amino acid to (2R, 4S) 2,4-diaminopentanoic
      acid via a radical-based mechanism. The crystal structure of OAM reveals that
      His225 is within hydrogen bond distance to the PLP phenolic oxygen, and may
      influence the pK(a) of the Schiff base during radical rearrangement. To evaluate
      the role of His225 in radical stabilization and catalysis, the residue was
      substituted with a glutamine and alanine. The H225Q and H225A variants have a 3-
      and 10-fold reduction in catalytic turnover, respectively, and a decrease in
      catalytic efficiency (7-fold for both mutants). Diminished catalytic performance
      is not linked to an increase in radical-based side reactions leading to enzyme
      inactivation. pH-dependence studies show that k(cat) increases with the
      ionization of a functional group, but it is not attributed to His225. Binding of
      2,4-diaminobutyric acid to native OAM leads to formation of an overstabilized 2,4
      diaminobutyryl-PLP derived radical. In the H225A and the H225Q mutants, the
      radical forms and then decays, as evidenced by accumulation of cob(III)alamin.
      From these data, we propose that His225 enhances radical stability by acting as a
      hydrogen bond acceptor to the phenolic oxygen, which favors the deprotonated
      state of the imino nitrogen and leads to greater resonance stabilization of the
      2,4-diaminobutyryl-PLP radical intermediate. The potential role of His225 in
      lowering the activation energy barrier to mediate PLP-dependent radical
      rearrangement is discussed.

PMID- 21899874
TI  - Chemometric data analysis application to Sparus aurata samples from two offshore
      farming plants along the Apulian (Italy) coastline.
AB  - The levels of polychlorodibenzo-p-dioxins (PCDDs), polychlorodibenzofurans
      (PCDFs), dioxin-like polychlorobiphenyls (DL-PCBs), non-dioxin-like
      polychlorobiphenyls (NDL-PCBs), and polybromodiphenyl ethers (PBDEs) in fish
      collected from two marine offshore farming plants were determined. Each sample
      was constituted by specimens of the same size collected at the same time in four
      different seasons along the farming year. The feeds given were of industrial
      origin and the plants were positioned in two different sites respectively exposed
      to different environmental characteristics. A chemometric approach was applied to
      interpret the subtle differences observed in fish body burdens across the three
      chemical groups taken into consideration. The approach consisted in a stepwise
      multivariate process including a hierarchical cluster analysis (CA) and a linear
      discriminant analysis (DA). The two main clusters determined by CA were subjected
      to the canonical DA, backward and forward selection procedures to select the best
      discriminative functions. A clear temporal and spatial discrimination was found
      among the samples. Across the three chemical groups, the monthly separation
      seemed to depend on the growth process and the main exposure was due to the feed.
      In addition, the two plants differed significantly from the environmental point
      of view and the most important discriminating group of chemicals were the NDL
      PCBs. The approach resulted really effective in discriminating the subtle
      differences and in individuating suggestions to improve the quality of culturing
      conditions.

PMID- 21899875
TI  - 28-Homobrassinolide mitigates boron induced toxicity through enhanced antioxidant
      system in Vigna radiata plants.
AB  - The objective of this study was to establish relationship between boron induced
      oxidative stress and antioxidant system in Vigna radiata plants and also to
      investigate whether brassinosteroids will enhance the level of antioxidant system
      that could confer tolerance to the plants from the boron induced oxidative
      stress. The mung bean (V. radiata cv. T-44) plants were administered with 0.50,
      1.0 and 2.0 mM boron at 6 d stage for 7 d along with nutrient solution. At 13 d
      stage, the seedlings were sprayed with deionized water (control) or 10(-8) M of
      28-homobrassinolide and plants were harvested at 21 d stage to assess growth,
      leaf gas-exchange traits and biochemical parameters. The boron treatments
      diminished growth, water relations and photosynthetic attributes along with
      nitrate reductase and carbonic anhydrase activity in the concentration dependent
      manner whereas, it enhanced lipid peroxidation, electrolyte leakage, accumulation
      of H(2)O(2) as well as proline, and various antioxidant enzymes in the leaves of
      mung bean which were more pronounced at higher concentrations of boron. However,
      the follow-up application of 28-homobrassinolide to the boron stressed plants
      improved growth, water relations and photosynthesis and further enhanced the
      various antioxidant enzymes viz. catalase, peroxidase and superoxide dismutase
      and content of proline. The elevated level of antioxidant enzymes as well as
      proline could have conferred tolerance to the B-stressed plants resulting in
      improved growth, water relations and photosynthetic attributes.

PMID- 21899876
TI  - Record of PCB congeners, sorbents and potential toxicity in core samples in
      Indiana Harbor and Ship Canal.
AB  - Indiana Harbor and Ship Canal (IHSC) is an active navigational system that serves
      a heavily industrial area of southern Lake Michigan. We have determined the
      amount of polychlorinated biphenyls (PCBs), congener distributions, sorbent types
      and potential for dioxin-like PCB toxicity from two IHSC sediment cores. Vertical
      distributions of SigmaPCBs (sum of 161 individual or coeluting congeners) ranged
      from 410 to 91000 and 1800 to 41000 ng g(-1) dry weight (d.w.) for cores 1 and 2,
      respectively. Core 1 showed its highest accumulation rate for the year ~1979 and
      exhibits a strong Aroclor 1248 signal in sediments accumulating over the last 60
      years. It appears that from the late 1930s until the beginning of the 1980s there
      was a large and constant input of PCBs into this system. This pattern differs
      from lake cores from the Great Lakes region which commonly exhibit a rapid
      increase, a peak, followed by a sharp decrease in the PCB accumulation rates.
      Core 2 also has a strong Aroclor 1248 signal in the top layers, but deeper layers
      show evidence of mixtures of Aroclors and/or weathering processes. High levels of
      black carbon as a fraction of total organic carbon were found in both cores
      (median ~30%), which reflect the long history of local combustion sources. No
      strong relationship was found between SigmaPCB concentration and sorbents. Both
      cores contain dioxin-like PCBs that are highest in concentration below the
      surface. The high levels of PCBs in the deep sediments are of concern because of
      plans to dredge this system.

PMID- 21899877
TI  - Water- and sediment-quality effects on Pimephales promelas spawning vary along an
      agriculture-to-urban land-use gradient.
AB  - Many streams in the U.S. are "impaired" due to anthropogenic influence. For
      watershed managers to achieve practical understanding of these impairments, a
      multitude of factors must be considered, including point and nonpoint-source
      influence on water quality. A spawning assay was developed in this study to
      evaluate water- and sediment-quality effects that influenced Pimephales promelas
      (fathead minnow) egg production over a gradient of urban and agricultural land
      use in 27 small watersheds in Eastern Wisconsin. Six pairs of reproducing fathead
      minnows were contained in separate mesh cartridges within one larger flow-through
      chamber. Water- and sediment quality were sampled for an array of parameters. Egg
      production was monitored for each pair providing an assessment of spawning
      success throughout the 21-day test periods. Incidences of low dissolved oxygen
      (DO) in many of these streams negatively impacted spawning success. Nine of 27
      streams experienced DO less than 3.1mg/L and 15 streams experienced DO less than
      4.8mg/L. Low DO was observed in urban and agricultural watersheds, but the upper
      threshold of minimum DO decreased with increasing urban development. An increase
      in specific conductance was related to a decrease in spawning success. In
      previous studies for streams in this region, specific conductance had a linear
      relation with chloride, suggesting the possibility that chloride could be a
      factor in egg production. Egg production was lower at sites with substantial
      urban development, but sites with low egg production were not limited to urban
      sites. Degradation of water- and sediment-quality parameters with increasing
      urban development is indicated for multiple parameters while patterns were not
      detected for others. Results from this study indicate that DO must be a high
      priority watershed management consideration for this region, specific conductance
      should be investigated further to determine the mechanism of the relation with
      egg production, and water- and sediment-quality degrade in relation to urban
      influence.

PMID- 21899878
TI  - High levels of inorganic arsenic in rice in areas where arsenic-contaminated
      water is used for irrigation and cooking.
AB  - Rice is the staple food for the people of arsenic endemic South (S) and South
      East (SE) Asian countries. In this region, arsenic contaminated groundwater has
      been used not only for drinking and cooking purposes but also for rice
      cultivation during dry season. Irrigation of arsenic-contaminated groundwater for
      rice cultivation has resulted high deposition of arsenic in topsoil and uptake in
      rice grain posing a serious threat to the sustainable agriculture in this region.
      In addition, cooking rice with arsenic-contaminated water also increases arsenic
      burden in cooked rice. Inorganic arsenic is the main species of S and SE Asian
      rice (80 to 91% of the total arsenic), and the concentration of this toxic
      species is increased in cooked rice from inorganic arsenic-rich cooking water.
      The people of Bangladesh and West Bengal (India), the arsenic hot spots in the
      world, eat an average of 450g rice a day. Therefore, in addition to drinking
      water, dietary intake of arsenic from rice is supposed to be another potential
      source of exposure, and to be a new disaster for the population of S and SE Asian
      countries. Arsenic speciation in raw and cooked rice, its bioavailability and the
      possible health hazard of inorganic arsenic in rice for the population of S and
      SE Asia have been discussed in this review.

PMID- 21899879
TI  - Arsenic accumulation in irrigated agricultural soils in Northern Greece.
AB  - The accumulation of arsenic in soils and food crops due to the use of arsenic
      contaminated groundwater for irrigation has created worldwide concern. In the
      Chalkidiki prefecture in Northern Greece, groundwater As reach levels above
      1000MUg/L within the Nea Triglia geothermal area. While this groundwater is no
      longer used for drinking, it represents the sole source for irrigation. This
      paper provides a first assessment of the spatial extent of As accumulation and of
      As mobility during rainfall and irrigation periods. Arsenic content in sampled
      soils ranged from 20 to 513mg/kg inside to 5-66mg/kg outside the geothermal area.
      Around irrigation sprinklers, high As concentrations extended horizontally to
      distances of at least 1.5m, and to 50cm in depth. During simulated rain events in
      soil columns (pH=5, 0MUg As/L), accumulated As was quite mobile, resulting in
      porewater As concentrations of 500-1500MUg/L and exposing plant roots to high
      As(V) concentrations. In experiments with irrigation water (pH=7.5, 1500MUg
      As/L), As was strongly retained (50.5-99.5%) by the majority of the soils.
      Uncontaminated soils (<30mg As/kg) kept soil porewater As concentrations to below
      50MUg/L. An estimated retardation factor R(f)=434 for weakly contaminated soil
      (<100mg/kg) indicates good ability to reduce As mobility. Highly contaminated
      soils (>500mg/kg) could not retain any of the added As. Invoked mechanisms
      affecting As mobility in those soils were adsorption on solid phases such as
      Fe/Mn-phases and As co-precipitation with Ca. Low As accumulation was found in
      collected olives (0.3-25MUg/kg in flesh and 0.3-5.6MUg/kg in pits). However, soil
      arsenic concentrations are frequently elevated to far above recommended levels
      and arsenic uptake in faster growing plants has to be assessed.

PMID- 21899880
TI  - Tackling NCDs: a different approach is needed.

PMID- 21899881
TI  - The influence of surface topography of a porous perfluoropolyether polymer on
      corneal epithelial tissue growth and adhesion.
AB  - Design principles for corneal implants are challenging and include permeability
      which inherently involves pore openings on the polymer surface. These
      topographical cues can be significant to a successful clinical outcome where a
      stratified epithelium is needed over the device surface, such as with a corneal
      onlay or corneal repair material. The impact of polymer surface topography on the
      growth and adhesion of corneal epithelial tissue was assessed using porous
      perfluoropolyether membranes with a range of surface topography. Surfaces were
      characterised by AFM and XPS, and the permeability and water content of membranes
      was measured. Biological testing of membranes involved a 21-day in vitro tissue
      assay to evaluate migration, stratification and adhesion of corneal epithelium.
      Similar parameters were monitored in vivo by surgically implanting membranes into
      feline corneas for up to 5 months. Data showed optimal growth and adhesion of
      epithelial tissue in vitro when polymer surface features were below a 150 nm RMS
      value. Normal processes of tissue growth and adhesion were disrupted when RMS
      values approached 300 nm. Data from the in vivo study confirmed these findings.
      Together, outcomes demonstrated the importance of surface topography in the
      design of implantable devices that depend on functional epithelial cover.

PMID- 21899883
TI  - Perfluorodecalin-enriched fibrin matrix for human islet culture.
AB  - Disruption of microenvironment and decrease in oxygen supply during isolation and
      culture lead to pancreatic islet injury and their poor survival after
      transplantation. This study aimed to create a matrix for culturing islets, using
      fibrin as scaffold and perfluorodecalin as oxygen diffusion enhancing medium.
      Human pancreatic islets were divided in four groups: control, islets cultured in
      fibrin, islets in fibrin containing non-emulsified perfluorodecalin, and finally
      islets in fibrin supplemented with emulsified perfluorodecalin. After an
      overnight culture, cell damage (viability, proinsulin and insulin unregulated
      release, apoptosis (caspase-3 activation), secretory function, and presence of
      hypoxia markers (HIF-1a and VEGF expression) were assessed. Islets cultured in a
      matrix, had similar islet viability to controls (no matrix) but decreased levels
      of active caspase-3 and unregulated hormone release, but high level of hypoxia
      markers expression. Although the supplementation of fibrin with non-emulsified
      perfluorodecalin improves secretory response, there was no decrease in hypoxia
      markers expression. In contrast, emulsified perfluorodecalin added to the matrix
      improved islet function, islet viability and maintained level of hypoxia markers
      similar to control. Fibrin matrix supplemented with emulsified perfluorodecalin
      can provide a beneficial physical and chemical environment for improved
      pancreatic human islet function and viability in vitro.

PMID- 21899882
TI  - Actin and ERK1/2-CEBPbeta signaling mediates phagocytosis-induced innate immune
      response of osteoprogenitor cells.
AB  - Wear particles at the host bone-implant interface are a major challenge for
      successful bone implant arthoplasties. Current understanding of aseptic loosening
      consists of macrophage-mediated inflammatory responses and increasing
      osteoclastogenesis, which lead to an imbalance between bone formation and
      resorption. Despite its significant role in bone regeneration and implant
      osteointegration, the osteoprogenitor response to wear particles has been
      examined recent years. More specifically, the intracellular mechanism of
      osteoprogenitor mediated inflammation has not been fully elucidated. In this
      study, we examined the role of osteoprogenitors and the cellular mechanism by
      which metal wear particles elicit an inflammatory cascade. Through both in vivo
      and in vitro experiments, we have demonstrated that osteoprogenitor cells are
      capable of initiating inflammatory responses by phagocytosing wear particles,
      which lead to subsequent accumulation of macrophages and osteoclastogenesis, and
      the ERK_CEBP/beta intracellular signaling is a key inflammatory pathway that
      links phagocytosis of wear particles to inflammatory gene expression in
      osteoprogenitors. AZD6244 treatment, a potent inhibitor of the ERK pathway,
      attenuated particle mediated inflammatory osteolysis both in vivo and in vitro.
      This study advances our understanding of the mechanisms of osteoprogenitor
      mediated inflammation, and provides further evidence that the ERK_CEBP/beta
      pathway may be a suitable therapeutic target in the treatment of inflammatory
      osteolysis.

PMID- 21899884
TI  - Contribution of different placental cells to the expression and stimulation of
      antimicrobial proteins (AMPs).
AB  - The placenta is a major barrier that prevents potentially infectious agents from
      causing fetal diseases or related complications during pregnancy. Therefore, we
      postulated that the placenta might express a broad repertoire of antimicrobial
      proteins as well as inflammatory chemokines and cytokines to combat invading
      microorganisms. Here we demonstrate that placental cells indeed express a wide
      range of AMPs (antimicrobial peptides and proteins) including
      bactericidal/permeability-increasing protein (BPI), secretory leukocyte protease
      inhibitor (SLPI), human beta-defensin 2 (hBD2), acyloxyacyl hydrolase (AOAH), and
      cathelicidin (CAP18). In addition, these cells also secrete pro-inflammatory
      cytokines and chemokines upon stimulation with bacterial ligands. Notably, we
      show that BPI expression by placental cells could be completely attributed to
      granulocytes while highly purified placental trophoblasts expressed only a subset
      of the AMPs like SLPI. Unexpectedly, trophoblast AMPs did not exhibit inducible
      secretion in response to various TLR ligands and further investigations showed
      that the unresponsiveness of trophoblasts to lipopolysaccharide (LPS) was due to
      a lack of TLR4 expression. In summary, we have shown that the expression of
      different AMPs can be allocated to various cells in the placenta and the
      repertoire of the AMPs expressed by placental cells is a result of a cooperation
      of leukocytes as well as cells from embryonic origin.

PMID- 21899886
TI  - Acquisition of the novel ABL kinase domain mutation T315L in a relapsed
      Philadelphia-positive acute lymphoblastic leukemia patient.

PMID- 21899885
TI  - High expression of IGFBP2 is associated with chemoresistance in adult acute
      myeloid leukemia.
AB  - Insulin-like growth factor (IGF) signaling plays an important role in many tumors
      and overexpression of IGF Binding Protein (IGFBP) 2 has been associated with
      adverse outcome in childhood leukemia. Here, we evaluated IGFBP2 mRNA expression
      and its prognostic implications in 99 adult acute myeloid leukemia (AML) patients
      by quantitative real-time RT-PCR. High IGFBP2 was associated with a high
      incidence of primary resistant disease (IGFBP2 high 65%, IGFBP2 low 32%; P=0.02)
      and was independently predictive for therapy resistance [OR 3.6 (95% CI 1.2-11);
      P=0.02] in multivariate analyses. Gene-expression profiling revealed an up
      regulation of genes implicated in leukemogenesis (MYB, MEIS1, HOXB3, HOXA9) and
      genes associated with adverse outcome (ERG, WT1) in patients with high IGFBP2
      expression. Thus, our data suggest a role of IGFBP2 and IGF signaling in
      chemoresistance of AML. Patients with high IGFBP2 expression might benefit from
      molecular therapies targeting the IGF pathway.

PMID- 21899887
TI  - A rare case of childhood precursor B-cell lymphoblastic lymphoma in the mandible.

PMID- 21899888
TI  - Oxidative biomarkers in leaf tissue of barley seedlings in response to aluminum
      stress.
AB  - Cellular responses to Al-stress in Hordeum vulgare seedling bioassay were
      evaluated with an objective to identify the possible biomarkers in leaf tissue
      that would be best suited to biomonitor aluminum (Al) in the environment.
      Germinating seeds were treated with different concentrations of AlCl(3) at pH 4.5
      for 12h. Al-uptake and accumulation in root and leaf, generation of reactive
      oxygen species (ROS: O(2)(-), H(2)O(2) and ()OH), cell death, activity of
      antioxidant enzymes: catalase, superoxide dismutase, guaiacol peroxidase,
      ascorbate peroxidase, lipid peroxidation, protein oxidation, DNase activity and
      DNA damage were measured in leaf tissue of the seedlings on day 6 after
      treatment. The above parameters assessed in leaf tissue that followed a dose
      response exhibited significant correlation with concentration of Al(3+) in
      experimental solution as well as in root tissue. The findings underscored the
      sensitivity as well as potential of Hordeum vulgare seedling bioassay for
      biomonitoring of Al in the ambient environment.

PMID- 21899889
TI  - How research ethics' protections can contribute to public policy: the case of
      community treatment orders.
AB  - Though community treatment orders (CTOs) were first used in 1986 in Australia,
      debate about their clinical and ethical merits continues even today. For some,
      the benefits of reduced frequency and duration of involuntary hospitalizations
      are believed to adequately outweigh the harms of restricted liberties in
      community living. For others, however, such benefits are believed to be
      achievable by simply arranging integrated, devoted community resources sans any
      threat of forced re-hospitalization. In response to this enduring controversy,
      this article examines the ethical merits of community orders using a novel
      approach. "Novel" because the examination is based on research ethics and its
      foundational principles. When hospital and community clinicians, family members,
      consumer/survivors, and advocacy groups discussed the idea of amending Ontario's
      mental health legislation to permit CTOs in the late 1990s, evidence of their
      effects and efficacy was very limited. Moreover, an order was characterized much
      like standard pharmacological or medical therapies because the person or an
      appropriate substitute decision maker's consent was necessary to authorize the
      order or make it valid. These two factors prompted this retrospective analysis:
      if CTOs--as a public policy initiative--had been treated like most other
      promising therapies, would any different ethics-related concerns have been raised
      that, in turn, would have benefited the public debate and the legislature's
      decisions? In other words, if respected safeguards that apply to new drugs and
      medical devices had applied to CTOs, would anything have changed?

PMID- 21899890
TI  - Psychopathy, intelligence and conviction history.
AB  - The current study examined the relationship between psychopathy, intelligence and
      two variables describing the conviction history (length of conviction and number
      of prior convictions). It was hypothesized that psychopathy factors
      (interpersonal and antisocial factors assuming a 2-factor model or interpersonal,
      affective, lifestyle and antisocial factors assuming a 4-factor model) would be
      related in different ways to IQ scores, length of conviction and number of prior
      convictions. Psychopathy and IQ were assessed using the PCL:SV and the CFT 20-R
      respectively. Results indicated no association between interpersonal psychopathy
      features (Factor 1, two-factor model), IQ and the number of prior convictions but
      a positive association between Factor 1 and the length of conviction. Antisocial
      features (Factor 2, two-factor model) were negatively related to IQ and the
      length of conviction and positively related to the number of prior convictions.
      Results were further differentiated for the four-factor model of psychopathy. The
      relationship between IQ and psychopathy features was further assessed by
      statistically isolating the effects of the two factors of psychopathy. It was
      found that individuals scoring high on interpersonal features of psychopathy are
      more intelligent than those scoring high on antisocial features, but less
      intelligent than those scoring low on both psychopathy features. The results
      underpin the importance of allocating psychopathic individuals to subgroups on
      the basis of personality characteristics and criminological features. These
      subgroups may identify different types of offenders and may be highly valuable
      for defining treatment needs and risk of future violence.

PMID- 21899891
TI  - Hypoalgesic and motor effects of kaltenborn mobilization on elderly patients with
      secondary thumb carpometacarpal osteoarthritis: a randomized controlled trial.
AB  - OBJECTIVE: This study evaluated the effects of Kaltenborn manual therapy on
      sensory and motor function in elderly patients with secondary carpometacarpal
      osteoarthritis (CMC OA). METHOD: Twenty-nine female patients with secondary CMC
      OA (70-90 years old) were randomized into Kaltenborn manual therapy and sham
      groups. This study was designed as a double-blind, randomized controlled trial
      (RCT). Therapy consisted of Kaltenborn mobilization of posterior-anterior gliding
      with distraction in grade 3 of the carpometacarpal (CMC) joint of the dominant
      hand during 6 sessions over 2 weeks. Pain was measured by algometry, as the
      pressure pain threshold (PPT) at the CMC joint and tubercle of the scaphoid bone.
      The tip and tripod pinch strength was also measured. Grip strength was measured
      by a grip dynamometer. Measurements were taken before treatment and after 1 week
      (first follow-up [FU]) and 2 weeks (second FU). RESULTS: All values in the sham
      group remained unchanged during the treatment period. In the treated group, the
      PPT in the CMC joint was 2.98 +/- 0.30 kg/cm(2), which increased after treatment
      to 4.07 +/- 0.53, and was maintained at the same level during the first FU (3.46
      +/- 0.31) and second FU (3.84 +/- 0.36). Similarly, the PPT in the scaphoid bone
      was 3.61 +/- 0.29 kg/cm(2), which increased after treatment to 4.87 +/- 0.37, and
      was maintained at the same level during the first FU (4.44 +/- 0.43) and second
      FU (4.22 +/- 0.32). In contrast, we found no differences in the tip, tripod
      pinch, and grip strength measurements between the treatment and sham groups.
      CONCLUSIONS: This study showed that Kaltenborn manual therapy decreased pain in
      the CMC joint and scaphoid bone areas of elderly female patients; however, it did
      not confer an increase in motor function in patients with CMC OA.

PMID- 21899892
TI  - Clinical tests for screening and diagnosis of cervical spine myelopathy: a
      systematic review.
AB  - OBJECTIVE: The purpose of this review was to investigate the diagnostic accuracy
      for screening and confirmation of clinical tests for cervical spine myelopathy
      (CSM) and to investigate the quality of the studies that have investigated these
      values. METHODS: This study was a systematic review that used the Preferred
      Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Search terms
      for PubMed included myelopathy; diagnosis, differential; sensitivity and
      specificity; and physical examination. Search terms for Cumulative Index to
      Nursing and Allied Health Literature were limited to myelopathy and sensitivity
      and specificity. Qualitative assessment included report of diagnostic accuracy
      metrics (sensitivity, specificity, and positive and negative likelihood ratios)
      and quality scores using the Quality Assessment of Diagnostic Accuracy Studies
      tool. Scores were created for single tests and clustered test findings. RESULTS:
      After evaluation, 12 full-text articles were selected, scored, and tabulated.
      Nearly all of the 18 tests demonstrated high levels of specificity and low levels
      of sensitivity, suggesting that they are poor screening tools. Only one study was
      scored as high quality. One study involved clustering of test findings but was
      considered low quality. CONCLUSION: Nearly all of the clinical tests for CSM seem
      to be poor screening tools, which implies that manually oriented clinicians may
      perform treatment methods in a situation of doubt or uncertainly. More high
      quality studies are needed, and manual therapists need to be cognizant that the
      current clinical tests for CSM lack strong diagnostic accuracy measures that are
      necessary for clinical decision making.

PMID- 21899893
TI  - MAPK/AP-1 activation mediates TLR2 agonist-induced SPLUNC1 expression in human
      lung epithelial cells.
AB  - BACKGROUND: Short Palate Lung and Nasal epithelium Clone 1 (SPLUNC1) is a newly
      described host defense protein, primarily expressed in large airway epithelial
      cells. Reduced SPLUNC1 has been reported in allergic and cigarette smoke-exposed
      airways. We found that Mycoplasma pneumoniae increases SPLUNC1 in airway
      epithelium in part via activating TLR2-NF-kappaB pathway. However, the
      contribution of additional signaling pathways to TLR2-mediated SPLUNC1 expression
      remains unclear. In the present study, we investigated if TLR2-induced mitogen
      activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling regulates
      SPLUNC1 expression in human lung epithelial cells. METHODS: Human lung epithelial
      NCI-H292 cells were stimulated with a TLR2 agonist Palmitoyl (3)-Cys-Ser-Lys (4)
      OH (Pam(3)CSK(4)). MAPK/AP-1 activation and its role in SPLUNC1 regulation were
      investigated by Western blot, c-Jun activation assay, chromatin
      immunoprecipitation (ChIP) and real-time PCR. SPLUNC1 promoter activity was
      assessed by a luciferase reporter assay. RESULTS: Pam(3)CSK(4) increased SPLUNC1
      expression in NCI-H292 cells in a dose- and time-dependent manner, and enhanced
      SPLUNC1 promoter activity. Pam(3)CSK(4)-treated cells demonstrated activated MAPK
      and c-Jun compared to untreated cells. ChIP assay indicated increased c-Jun
      binding to the SPLUNC1 promoter following Pam(3)CSK(4) stimulation. Inhibition of
      ERK1/2 significantly reduced Pam(3)CSK(4)-mediated c-Jun activation and SPLUNC1
      expression. CONCLUSIONS: Our results for the first time demonstrate that TLR2
      mediated MAPK/AP-1 activation up-regulates lung epithelial SPLUNC1 expression at
      the transcriptional level. Understanding SPLUNC1 gene regulation should provide
      more specific therapeutic targets to restore deficient SPLUNC1 production in
      diseased airways.

PMID- 21899894
TI  - Evaluating the conformation of recombinant domain I of beta(2)-glycoprotein I and
      its interaction with human monoclonal antibodies.
AB  - Pathogenic antiphospholipid antibodies (aPL) cause the antiphospholipid syndrome
      (APS) by interacting with domain I (DI) of beta-2-glycoprotein I (beta(2)GPI).
      The aPL/beta(2)GPI complex then exerts pathogenic effects on target cells. We
      previously described periplasmic bacterial expression of native and mutated
      variants of DI, and reported the presence of immunodominant epitopes at positions
      8-9 (D8/D9) and position 39 (R39). Mutations at these positions strongly
      influenced the ability of recombinant DI to bind patient-derived IgG aPL and to
      inhibit pathogenic effects of these aPL in a mouse model of APS. We now describe
      an improved cytoplasmic bacterial expression system allowing higher yield of DI.
      We demonstrate that the nuclear magnetic resonance (NMR) spectra of a (15)N,(13)C
      isotope-labelled sample of the recombinant DI protein exhibit properties
      consistent with the structure of DI in crystal structure of intact beta(2)GPI.
      Mutations at D8/D9 and R39 had limited impact on the NMR spectrum of DI
      indicating maintenance of the overall fold of the DI domain. We investigated
      interactions between five variants of DI and ten monoclonal human IgG antibodies,
      all derived from the IgG aPL antibody IS4 by sequence manipulation and in vitro
      expression. Arginine residues at positions 100 and 100g in IS4V(H) CDR3 play a
      particularly important role in binding to DI, but this is unlikely to be due to
      electrostatic interactions with negatively charged amino acids on DI. Both the
      strength of binding to DI and the ability to discriminate different DI variants
      varies between the different IgG antibodies tested. There was no simple
      relationship between these binding properties and antibody pathogenicity.

PMID- 21899895
TI  - Preliminary study of Internet addiction and cognitive function in adolescents
      based on IQ tests.
AB  - The potential relationship between Internet addiction and certain cognitive
      function problems has been suggested by several studies. However, few or no
      studies have examined the differences in cognitive functioning between persons
      addicted to the Internet and persons not addicted using a standard
      neuropsychological test. This study screened 253 middle school students and 389
      high school students for Internet addiction and compared 59 Internet-addicted
      students with 43 non-addicted students using an IQ test. The Internet-addicted
      group had comprehension sub-item scores that were significantly lower than those
      of the non-addicted group. As the comprehension item reflects ethical judgement
      and reality testing, there may be a relationship between Internet addiction and
      weak social intelligence. Earlier onset of Internet addiction and longer
      addiction duration were associated with lower participant performance in areas
      related to attention. As this study is a cross-sectional study, it is not clear
      whether the persons who display weak cognitive functioning are susceptible to
      Internet addiction or if Internet addiction causes cognitive problems. However,
      as brain development remains active during adolescence, the possibility that
      Internet addiction adversely affects the cognitive functioning of adolescents
      cannot be ruled out.

PMID- 21899896
TI  - High intravascular tissue factor expression in dogs with idiopathic immune
      mediated haemolytic anaemia.
AB  - A high mortality occurs in dogs with idiopathic immune-mediated haemolytic
      anaemia (IMHA) during the first 2 weeks after the diagnosis. The aim of this
      study was to investigate the inflammatory response and coagulation abnormalities
      in dogs with IMHA in relation to the prognosis and to establish the contribution
      of whole blood tissue factor (TF) and IL-8 gene expressions. Gene expressions in
      dogs with IMHA were compared to healthy dogs, dogs with DIC, dogs with sepsis,
      and in two groups of dogs that underwent intensive care treatment but had no
      evidence for either DIC or sepsis. The whole blood TF and IL-8 expressions were
      up regulated in all non-IMHA groups. Similarly, the TF expression in IMHA dogs
      was high, but the intravascular IL-8 expression was not increased. The dogs with
      IMHA had a pronounced inflammatory response that included a high WBC, left shift
      and monocytosis in comparison to the other disease groups. Coagulation factor
      activities in IMHA dogs were decreased fitting consumptive coagulopathy and the
      acute phase proteins FVIII and fibrinogen were increased. The platelet parameters
      suggested platelet activation and high platelet turnover in IMHA dogs. The model
      that best explained mortality contained monocytosis, increased activated partial
      thromboplastin time and elevated creatinine. Whole blood TF gene expression is up
      regulated and may contribute to consumptive coagulopathy in dogs with IMHA.
      Increased TF expression by activated platelets is an alternative explanation and
      should be investigated.

PMID- 21899897
TI  - Mitochondrial interference by anti-HIV drugs: mechanisms beyond Pol-gamma
      inhibition.
AB  - The combined pharmacological approach to the treatment of HIV infection, known as
      highly active antiretroviral therapy (HAART), has dramatically reduced AIDS
      related morbidity and mortality. However, its use has been associated with
      serious adverse reactions, of which those resulting from mitochondrial
      dysfunction are particularly widespread. Nucleos(t)ide-reverse transcriptase
      inhibitors (NRTIs) have long been considered the main source of HAART-related
      mitochondrial toxicity due to their ability to inhibit Pol-gamma, the DNA
      polymerase responsible for the synthesis of mitochondrial DNA. Nevertheless,
      accumulating evidence points to a more complex relationship between these
      organelles and NRTIs. Also, alternative pathways by which other groups of anti
      HIV drugs (non-nucleoside reverse transcriptase inhibitors and protease
      inhibitors) interfere with mitochondria have been suggested, although their
      implications, both pharmacological and clinical, are open to debate. This review
      aims to provide a comprehensive overview of the mechanisms and factors which
      influence the mitochondrial involvement in the toxicity of all three major
      classes of anti-HIV drugs.

PMID- 21899898
TI  - Determinants of acute hospital care use by elderly patients in Italy from 1996 to
      2006.
AB  - To determine the trend of elderly hospitalization rates in Italy, following the
      economic rationalization of health systems in Western countries, and to evaluate
      which alternatives to acute hospitalization have been developed during the period
      1996-2006 an ecological observational study has been carried out. Data from the
      Italian Hospital-Discharge Registries (HDRs) of the years 1996, 2001, and 2006
      have been analyzed in order to assess the variations among the elderly in terms
      of hospitalization rates, hospital stay, and bed rates. The results were compared
      with nursing home admission rates and home care offer. Relations among these
      variables were explored by univariate and multivariate analyses. Elderly hospital
      admission rates decreased in Italy from 324.2/1000 in 1996, to 258.7 in 2006.
      Mean hospital stay of elderly patients was 9.4 days in 2006, 9.5 in 2001 and 10.1
      in 1996. A multivariate linear regression model was statistically significant in
      explaining the variations in hospitalization rates (F: 5.68; p=0.004; R(2)=0.77).
      The main determinants linked to such variations were the bed rate (beta=0.67;
      p=0.004) and the hospital length of stay (beta=-0.77; p=0.03). The analysis
      showed a reduction in hospitalization rates among the elderly, which was not
      counterbalanced by an increased offer of home care and/or nursing home services,
      but was mainly linked to a decrease in the supply of acute beds, with possible
      consequences on the quality of health care.

PMID- 21899899
TI  - Predictors of functional capacity changes in a US population of Medicare home
      health care (HHC) patients with heart failure (HF).
AB  - PURPOSE: Functional capacity is widely recognized as a key factor in maintaining
      the ability of older people to live independently and safely at home. Promoting
      functional capacity is an important priority particularly in HHC. The purpose of
      the study was to examine predictors of functional capacity change among HHC
      patients with HF. MATERIALS AND METHODS: Clinical and administrative data from
      2005 from the Medicare Chronic Conditions Warehouse were linked at the population
      level for HHC patients with a primary diagnosis of HF. The primary outcome was
      change in functional capacity score from HHC admission to HHC discharge. RESULTS:
      Over the course of the episode (M=44 days), most (70%) patients improved, 15.6%
      stayed the same, and 14.4% declined in activities of daily living (ADL) scores.
      The mean change score was modest (mean=-0.74, SD=1.11) with a median change of 
      0.58. Multivariate analyses (R(2)=0.23) showed that the largest influence was the
      admission ADL score followed by receiving any physical therapy (PT), admission
      ability to manage oral medications, cognitive functioning, rehabilitation
      prognosis, and urinary incontinence. DISCUSSION: There is a modest rate of
      improvement from admission to discharge that likely represents the progressive
      nature of HF and/or the short time frames over which HHC is provided. Providers
      may want to use the predictive factors to identify patients most at risk for
      functional decline.

PMID- 21899900
TI  - Admission Norton scale scores (ANSS) are associated with post-operative
      complications following spine fracture surgery in the elderly.
AB  - We sought to determine if low ANSS, usually associated with high pressure ulcer
      risk, are also associated with post-operative complications following spine
      fracture surgery in the elderly. This was a retrospective cross-sectional study
      conducted at the division of orthopedic surgery in a tertiary medical center
      between January 2008 and October 2010. The medical charts of consecutive elderly
      (>= 65 years) patients admitted for spine fracture surgery were studied for the
      following measurements: ANSS, demographic data, co-morbidities, and post
      operative complications. Except for pressure ulcers, post-operative complications
      included: acute coronary syndrome, acute renal failure, confusion, pneumonia,
      urinary tract infection, venous thromboembolism, and wound infection. The final
      cohort included 90 patients: 66 (73.3%) females and 24 (26.7%) males. Mean age
      for the entire cohort was 78.9 +/- 0.7 years. Most patients had lumbar fractures
      (n=49; 54.4%) or thoracal fractures (n=26; 28.9%). Most patients underwent
      kyphoplasty (n=65; 72.2%). Mean ANSS was 15.9 +/- 0.3, and 29 (32.2%) patients
      had low (<15) ANSS. Patients with low ANSS had significantly more post-operative
      complications relative to patients with high ANSS (1.0 +/- 0.2 vs. 0.2 +/- 0.1;
      p<0.0001). Among all post-operative complications, urinary tract infection was
      independently associated with ANSS (p<0.0001). Binary regression analysis showed
      that ANSS were independently associated with post-operative complications
      (p=0.001). We conclude that low ANSS are associated with post-operative
      complications and urinary tract infection in particular, following spine fracture
      surgery in the elderly. Hence, the Norton scoring system may be used for
      predicting and preventing post-operative complications in this population.

PMID- 21899901
TI  - Familial Brugada syndrome unmasked by carbon monoxide intoxication.

PMID- 21899902
TI  - Non-invasive assessment of endothelial shear stress and coronary stiffness using
      multislice computed tomography.

PMID- 21899903
TI  - Myocardial iron homeostasis in advanced chronic heart failure patients.
AB  - BACKGROUND: Although, correction of iron deficiency and/or anemia in heart
      failure (HF) with iron seems promising, little is known about myocardial iron
      load and homeostasis. Moreover iron supplementation indications are solely based
      on iron serum markers. The purpose was to assess myocardial iron (M-Iron),
      ferritin (M-FR), transferrin receptor (M-sTfR) in HF in relation to serum Iron
      markers. METHODS AND RESULTS: Study group 33 patients, left/right ventricle
      (LV/RV) (LVEDV 245 +/- 84 ml; LVESV 189 +/- 85 ml; LVEF 22 +/- 11%; RVD 32 +/- 10
      mm), NTproBNP (5464 +/- 4825 pg/ml). Iron homeostasis assessment serum: iron, FR,
      transferrin/saturation (TSAT), sTfR; myocardial: M-Iron (Instrumental Neutron
      Activation Analysis, MUg/g), M-FR, M-sTfR (ELISA - ng/mg protein) in the
      explanted failing hearts (FH), compared to non-failing hearts (NFH n=11). In FH
      as compared to NFH, M-Iron was reduced in RV (174 +/- 45 vs 233 +/- 97,
      respectively, p=0.07), LV (189 +/- 58 vs 265 +/- 119, p=0.04), without
      significant changes in M-FR/M-sTfR. Out of all serum iron markers only sTfR was
      negatively correlated with M-Iron in either ventricle (RV r=-0.44, p=0.03, LV r=
      0.38, p=0.07). With regard to serum iron status, based on TSAT, patients were
      divided into two subgroups: reduced (TSAT<15%; n=11) and not-reduced serum iron
      (TSAT >= 15%; n=22). Both subgroups had similar grade of LV/RV dysfunction, NT
      proBNP levels. M-FR was lower in TSAT<15% than in TSAT >= 15% (LV -31 +/- 26 vs
      46 +/- 29; p=0.07) and (RV -24 +/- 24 vs 43 +/- 29; p=0.02), without differences
      in M-Iron and M-sTfR. CONCLUSIONS: In HF, M-Iron levels were reduced. Serum iron
      markers did not reflect M-Iron levels, except for serum sTfR. In reduced serum
      iron group, decrease in myocardial storage protein M-FR was observed.

PMID- 21899904
TI  - Perceived risk and strategy efficacy as motivators of risk management strategy
      adoption to prevent animal diseases in pig farming.
AB  - For Dutch fattening pig farms, this study explored (1) farmers' perceptions
      towards animal disease risks and animal health risk management; (2) factors
      underlying farmers' adoption of the two risk management strategies, namely,
      biosecurity measures and animal health programs. The risks included endemic and
      epidemic diseases. Data were obtained through a questionnaire (n=164). A
      behavioral model was developed using the Health Belief Model and tested using
      structural equation modeling. Endemic and epidemic diseases were regarded as an
      operational and catastrophic risk, respectively. Farmers considered severity of
      epidemics as slightly more important, compared to endemics. For both disease
      categories, farmers valued biosecurity measures as a more effective strategy than
      animal health programs. In the behavioral model, perceived benefits in terms of
      strategy efficacy was the strongest direct predictor of strategy adoption. Other
      behavioral components had a minor indirect effect, namely, via perceived
      benefits, and only in case of biosecurity measures. The indirect effect path did,
      however, vary per disease category. For endemics, such a path captured the effect
      of perceived susceptibility on perceived benefits mediated by perceived severity.
      For epidemics, it only captured the effect of perceived severity on perceived
      benefits. The results also revealed the importance of innate risk characteristics
      of farmers in their adoption decisions. In particular, general self-protection
      behavior directly contributed to decisions to adopt a certain strategy. The
      obtained knowledge highlights possible ways of improvement of programs aimed at
      promoting effective risk management strategies.

PMID- 21899905
TI  - Regulatory policy and the location of bio-pharmaceutical foreign direct
      investment in Europe.
AB  - This paper examines the relationship between cross-country differences in drug
      price regulation and the location of biopharmaceutical Foreign Direct Investment
      (FDI) in Europe. Simple theory predicts that price regulation in one country
      might affect total investment, but not the location of that investment, if sales
      are global. Nevertheless, some manufacturers threaten that the introduction of
      price regulation in a country will motivate them to move their investments to
      other countries. Are such threats cheap talk, or is there evidence that firms
      avoid price-controlling countries when making FDI location choices? We use data
      on 527 investments initiated in 27 European countries between 2002 and 2009 and
      find that investors are less likely to choose countries with price controls,
      after controlling for other determinants of investment. We also observe a
      relative decline in investment in countries that increased the stringency of
      regulatory regimes during our sample period. The effect is restricted to non
      manufacturing investments and is most robust for those related to administrative
      functions.

PMID- 21899906
TI  - Differences in cortical activity related to motor planning between experienced
      guitarists and non-musicians during guitar playing.
AB  - The influence of motor skill learning on movement-related brain activity was
      investigated using electroencephalography. Previous research has indicated that
      experienced performers display movement-related cortical potentials (MRCPs) of
      smaller amplitude and later onset compared to novices. Unfortunately, previous
      studies have lacked ecological validity with experimenters recording the MRCP
      prior to simple motor tasks and applying the results to more complex motor
      skills. This study replicated previous research using an ecologically valid motor
      skill; recording the MRCP from a group of experienced guitarists and a control
      group of non-musicians while they played a simple scale on the guitar. Results
      indicated no difference between groups in early motor planning. In contrast, the
      later, negative slope and motor potential components were of smaller amplitude
      and the negative slope began later in the experienced guitarists. The data may
      indicate that, for experienced guitarists, a reduced level of effort is required
      during the motor preparation phase of the task. These findings have implications
      for musical instrument learning as well as motor skill acquisition in general.

PMID- 21899907
TI  - Application of a bacteriophage cocktail to reduce Salmonella Typhimurium U288
      contamination on pig skin.
AB  - Multidrug-resistant Salmonella Typhimurium U288 is a significant pathogen of
      pigs, accounting for over half of all outbreaks on UK pig production premises.
      The potential of this serovar, and other salmonellae, to enter the food chain
      during the slaughtering process requires that efforts be made to reduce the
      prevalence of these bacteria at both the pre- and post-harvest stages of
      production. A bacteriophage cocktail (PC1) capable of lysing various Salmonella
      enterica serovars was designed using the broad host-range phage Felix 01, and
      three phages isolated from sewage. PC1 applied to pig skin experimentally
      contaminated with U288 achieved significant reductions (P<0.05) in Salmonella
      counts when stored at 4  degrees C over 96 h. Reductions of >1 log10 unit were
      observed when the ratio of phage applied was in excess of the bacterial
      concentration. The treatment was found to be effective at a multiplicity of
      infection (MOI) of 10 or above, with no significant reductions taking place when
      the MOI was less than 10. Under these conditions U288 counts of log10 4.1-4.3 CFU
      were reduced to undetectable levels following the application of PC1 to pig skin
      (>99% reduction). These data suggest phage cocktails could be employed post
      slaughter as a means to reduce Salmonella contamination of pig carcasses.

PMID- 21899908
TI  - Mechanisms involved in reduction of ochratoxin A produced by Aspergillus
      westerdijkiae using Debaryomyces hansenii CYC 1244.
AB  - Aspergillus westerdijkiae is one of the most relevant ochratoxin A (OTA)
      producing species within the Section Circumdati contaminating a number of
      agroproducts. The yeast Debaryomyces hansenii CYC 1244 was previously reported to
      be able to reduce growth and extracellular OTA produced by A. westerdijkiae. In
      this work, we examined several mechanisms possibly involved in this OTA reduction
      in in vitro experiments. OTA biosynthesis was evaluated by quantitation of
      expression levels of pks (polyketide synthase) and p450-B03 (cytochrome p450
      monooxygenase) genes using newly developed and specific real time RT-PCR
      protocols. Both genes showed significant lower levels in presence of D. hansenii
      CYC 1244 suggesting an effect on regulation of OTA biosynthesis at
      transcriptional level. High levels of removal of extracellular OTA were observed
      by adsorption to yeast cell walls, particularly at low pH (98% at pH 3). On the
      contrary, no evidences were obtained of absorption of OTA into yeast cells or the
      production of constitutively expressed enzymes that degrade OTA by D. hansenii
      CYC 1244. These results described the potential of this yeast strain as a safe
      and efficient biocontrol agent to decrease OTA in A. westerdijkiae and two
      important mechanisms involved which may permit its application at different
      points of the food chain.

PMID- 21899909
TI  - Biological characterization of two marine Bdellovibrio-and-like organisms
      isolated from Daya bay of Shenzhen, China and their application in the
      elimination of Vibrio parahaemolyticus in oyster.
AB  - Bdellovibrio-and-like organisms (BALOs) are a group of highly motile delta
      proteobacteria that prey on other gram-negative bacteria. However, nothing is
      known of the application potential of marine BALOs in safeguarding seafood
      safety. Here, biological characterization of two marine BALOs strains and their
      application in the elimination of Vibrio parahaemolyticus in oyster (Crassostrea
      ariakensis) at the laboratory scale were investigated. BALOs strains BDH12 and
      BDHSH06 were isolated from sediment of Daya bay in Shenzhen of China, with
      Shewanella putrefaciens strain 12 and V. parahaemolyticus strain SH06 as preys,
      respectively, when using double layer agar technique. They were identified as
      BALOs morphologically by transmission electron microscopy, while partial 16S rDNA
      sequencing analysis revealed that they showed no close relationships with members
      of the known genera Bdellovibrio, Bacteriolyticum, Bacteriovorax, or
      Peredibacter. Biological characterizations revealed that both strains had the
      optimal pH, salinity and temperature at 7.2, 3% and 30  degrees C,
      correspondingly. They could not utilize autoclaved, dead cells as hosts. Prey
      range analysis revealed that individually, BDH12 and BDHSH06 lysed 82.5% (47
      strains) and 84.2% (48 strains) of the total 57 preys tested respectively. In
      combination, they lysed 98.2% (56 of 57) strains. All strains of V.
      parahaemolyticus, Vibrio cholerae and Vibrio alginolyticus tested could be lysed
      by both strains. A 7-day laboratory-scale V. parahaemolyticus elimination
      experiment in oyster showed that in the control, the cell counts of total vibrios
      and V. parahaemolyticus strain Vp plus in water and in oyster intestines were on
      the rise, whereas in the BALOs treated groups, their numbers were down from
      8.09+/-0.05 log CFU/ml and 8.02+/-0.04 log CFU/ml to 2.39+/-0.01 log CFU/ml and
      2.33+/-0.01 log CFU/ml, respectively. The same patterns could also be observed in
      oyster intestines. Results of this study indicate the feasibility of using BALOs
      to biologically control or even eliminate V. parahaemolyticus in seafood oyster.

PMID- 21899910
TI  - Effect of Sanguis draconis (a dragon's blood resin) on streptozotocin- and
      cytokine-induced beta-cell damage, in vitro and in vivo.
AB  - The study was to examine the effects of Sanguis draconis ethanol extract (SDEE)
      on streptozotocin (STZ)- and cytokine-induced beta-cell damage. In vitro, SDEE
      did not cause cytotoxicity below 200 MUg/ml, and can prevent STZ (5mM)-induced
      cell death and apoptosis below 100 MUg/ml on RIN-m5F cells. SDEE inhibits IL
      1beta/IFN-gamma-stimulated NO, TNF-alpha release, and iNOS expression.
      Furthermore, SDEE suppressed the IL-1beta/IFN-gamma- or STZ-induced p65
      expression of NF-kappaB, which is associated with inhibition of IkappaB-alpha
      degradation. In vivo, treatment of ICR mice with STZ (100 mg/kg, i.p. single
      injection) resulted in hyperglycemia and hypoinsulinemia, which was further
      evidenced by blood glucose and plasma insulin. The diabetogenic effects of STZ
      were completely prevented when mice were orally administered with SDEE for 3
      weeks, however, the blood glucose and plasma insulin showed no significant change
      after SDEE administration alone. In addition, SDEE also can inhibit STZ-induced
      iNOS protein expression, pancreatic injury and lipid peroxidation. In
      conclusions, the molecular mechanism by which SDEE inhibits iNOS gene expression
      appears to involve the inhibition of NF-kappaB activation. These results suggest
      the possible therapeutic value of S. draconis and could be potentially developed
      into a novel drug for preventing the progression of diabetes mellitus.

PMID- 21899911
TI  - How patients with type 2 diabetes mellitus respond to motivational interviewing.
AB  - AIM: To determine how patients with type 2 DM feel about a motivational
      interviewing (MI) intervention designed to promote positive behavior change.
      METHOD: Qualitative study using focus groups conducted by the same facilitator.
      SETTING: Family or general internal medicine practice clinics affiliated with an
      academic medical center and a community general hospital. One site consisted of
      primarily low income Hispanic patients. PARTICIPANTS: Four focus groups
      consisting of nineteen adult patients with type 2 diabetes mellitus solicited
      from a large NIH-funded randomized controlled trial on MI and diabetes. RESULTS:
      Across and within group analysis was performed on transcripts of the taped
      interviews. Patient perceptions of standard care were largely negative, with
      several individuals describing paternalistic and demeaning attitudes. Five themes
      related to MI emerged: Nonjudgmental Accountability, Being Heard and Responded to
      as a Person, Encouragement and Empowerment, Collaborative Action Planning and
      Goal Setting, and Coaching rather than Critiquing. CONCLUSIONS: Some patients
      with type 2 diabetes are receptive to motivational interviewing which is a
      provider approach that is more patient-centered and empowering than traditional
      care.

PMID- 21899913
TI  - Computer simulation of structured treatment interruption for HIV infection.
AB  - The use of highly active antiretroviral therapy (HAART) for suppression of
      measurable levels of virus in the body has greatly contributed to restoration and
      preservation of the immune system in HIV positive patients. However, short and
      long term problems associated with HAART have led to proposals for alternative
      treatment strategies for controlling HIV infection. In particular, structured
      treatment interruptions (STIs) that consist of therapy withdrawal and re
      initiation according to specific criteria have been considered. The aim of these
      STIs was one or both of: (i) to stimulate the immune system to react to HIV, (ii)
      to allow re-emergence of wild-type virus and thereby reduce problems of drug
      resistance. However, a number of clinical trials of STIs have shown adverse
      outcomes for patients under discontinuous therapy, including serious health risks
      associated with treatment interruptions. In this paper we consider in some detail
      two of the larger clinical studies, namely, (a) strategies for management of anti
      retroviral therapy (SMART); (b) Staccato study. For each of these studies we
      perform computer simulations of the treatment strategies. These simulations
      suggest several underlying reasons for the adverse outcomes during treatment
      interruption. In particular, HIV infection exhibits rapid dynamic load changes,
      and therefore measurement based treatment regimes need to be carefully designed
      to avoid large transients in healthy CD4+ T cell count. Furthermore, repeated
      treatment interruptions may accelerate the emergence of resistant mutant virus
      and may increase the infection of long term reservoirs such as macrophages which
      will accelerate progression to AIDS.

PMID- 21899914
TI  - Raising the bar for systematic conservation planning.
AB  - Systematic conservation planning (SCP) represents a significant step toward cost
      effective, transparent allocation of resources for biodiversity conservation.
      However, research demonstrates important consequences of uncertainties in SCP and
      of basing methods on simplified circumstances involving few real-world
      complexities. Current research often relies on single case studies with unknown
      forms and amounts of uncertainty as well as low statistical power for
      generalizing results. Consequently, conservation managers have little evidence
      for the true performance of conservation planning methods in their own complex,
      uncertain applications. To build effective and reliable methods in SCP, there is
      a need for more challenging and integrated testing of their robustness to
      uncertainty and complexity, and much greater emphasis on generalization to real
      world situations.

PMID- 21899912
TI  - Contributing factors related to efficacy of the dipeptidyl peptidase-4 inhibitor
      sitagliptin in Japanese patients with type 2 diabetes.

PMID- 21899915
TI  - Complement polymorphisms: geographical distribution and relevance to disease.
AB  - The evolution of man has been characterised by recurrent episodes of migration
      and settlement with infectious disease a constant threat. This long history of
      demographic change, together with the action of evolutionary forces such as
      natural selection and genetic drift, has shaped human genetic diversity. In
      particular, the interaction between humans, pathogens and the environment has
      played a crucial role in generating patterns of human genetic variation. The
      complement system plays a crucial role in the early protective immune response
      after exposure to a pathogen. Pathogens, over time, have developed mechanisms to
      circumvent the effects of complement which in turn has led to development of a
      more complex complement system. During the evolution of the complement system
      genes coding complement proteins have evolved polymorphisms, some of which have a
      functional effect, and this may reflect human-pathogen interaction and
      geographical origin. An example is the polymorphism Ile62Val (rs800292 (A>G)) in
      the complement regulator Factor H gene which alters the susceptibility to age
      related macular degeneration (AMD), with the Ile62 polymorphism protecting
      against AMD. When sub-Saharan African and European populations are compared, the
      frequency of this polymorphism shows a very marked geographical distribution.
      Polymorphisms in other complement genes such as complement factor B show similar
      trends. This paper describes the geographical variation present in complement
      genes and discusses the implications of these observations. The analysis of
      genetic variation in complement genes is a promising tool to unravel mechanisms
      of host-pathogen interaction and can provide new insights into the evolution of
      the human immune system.

PMID- 21899916
TI  - Expression of let-7i is associated with Toll-like receptor 4 signal in coronary
      artery disease: effect of statins on let-7i and Toll-like receptor 4 signal.
AB  - Toll-like receptor (TLR) 4 signal plays an important role in immunity in coronary
      artery disease (CAD). A recent report has demonstrated that one of the let-7
      family microRNAs, let-7i, directly regulates Toll-like receptor 4 (TLR4)
      expression and contributes to immune response. The aim of this study was to
      determine whether let-7i is expressed with TLR4 in patients with CAD, and whether
      statins (atorvastatin or rosuvastatin) might affect these levels. To determine
      the effects of let-7i on TLR4 expression, human THP-1 cells transfected with let
      7i were analyzed for TLR4 levels. This study included 98 patients with CAD and 48
      subjects without CAD (non-CAD). Patients with CAD were randomized to 12 months of
      treatment with atorvastatin or rosuvastatin. Monocytes were obtained from
      peripheral blood at baseline and after 12 months of each type of therapy. Levels
      of let-7i and TLR4 were measured by real-time RT-PCR and FACS. Functional
      approaches to let-7i showed that transfection of let-7i into human THP-1 cells
      resulted in regulation of TLR4 expression. Levels of let-7i were lower in the CAD
      group than in the non-CAD group (0.98+/-0.42 vs. 4.65+/-1.21, P<0.01). There was
      a negative correlation between let-7i and TLR4 levels in patients with CAD (let
      7i vs. TLR4 mRNA: r=-0.60, P<0.01; let-7i vs. TLR4 MFI: r=-0.32, P<0.01). The
      atorvastatin group had markedly increased let-7i levels and diminished TLR4
      levels (all P<0.01), whereas the rosuvastatin group showed no change in these
      levels. This study suggests that atorvastatin down-regulates TLR4 signal via let
      7i expression in CAD patients, possibly contributing to the beneficial effects of
      atorvastatin on let-7i-mediated TLR4 signal in this disorder.

PMID- 21899917
TI  - Galectin-3 inhibits the chemotaxis of human polymorphonuclear neutrophils in
      vitro.
AB  - In the recent years, the participation of the animal lectin galectin (gal)-3 in
      inflammation and in host defence mechanisms was extensively studied. In vivo
      studies implied - among others - a role of gal-3 in the recruitment of
      polymorphonuclear neutrophils (PMN) to sites of bacterial infection. In that
      context, we asked the question whether gal-3 was chemotactic for PMN. Functional
      assays revealed that gal-3 was not chemotactic for PMN, but that it inhibited the
      spontaneous migration and the chemotaxis of PMN towards complement C5a,
      interleukin (IL)-8, or ATP. Moreover, gal-3 inhibited the shape change and the
      actin polymerisation of PMN that occurs in response to C5a or IL-8. By use of
      FITC-labelled gal-3, we found that it attached rapidly to the PMN membrane in a
      lactose-sensitive manner. In response to gal-3 the MAP kinase p38 was
      phosphorylated. This kinase is crucial for the migration of PMN towards end
      target chemokines, such as C5a, and is activated in response to C5a or IL-8. When
      PMN were preincubated with gal-3, the C5a-induced p38 phosphorylation was
      transiently enhanced, but eventually down-modulated. We conclude that by
      interfering with the chemokine-induced p38 phosphorylation gal-3 inhibits
      chemotaxis of PMN.

PMID- 21899918
TI  - Human Th1 and Th2 lymphocytes are distinguished by calcium flux regulation during
      the first 10 min of lymphocyte activation.
AB  - Preliminary data suggest different intracellular calcium handling of Th1 and Th2
      lymphocytes that may contribute to distinct cytokine production patterns. In this
      study we explored the contribution of the main mechanisms in charge of the
      elevation and decrease of cytoplasmic free calcium levels, i.e., the endoplasmic
      calcium release, the calcium release activated calcium (CRAC) channel, the
      mitochondrial calcium uniporter (MCU), the sarco/endoplasmic reticulum calcium
      ATPase (SERCA), and the plasma membrane calcium ATPase (PMCA) during the first 10
      min of activation in human Th1 and Th2 lymphocytes applying a kinetic flow
      cytometry approach. We isolated peripheral blood mononuclear cells from 10
      healthy individuals. Cells were stained with CD4, CXCR3 and CCR4 cell surface
      markers to identify Th1 and Th2 cells, respectively and loaded with Fluo-3/AM
      calcium sensitive dye. Cells were activated with phytohemagglutinine and
      alterations of cytoplasmic free calcium levels were monitored for 10 min after
      specific inhibition of the above mechanisms. Our results revealed delicate
      differences in calcium flux kinetics of Th1 and Th2 lymphocytes. The lower
      activity of MCU, and therefore of CRAC channels, along with the higher activity
      of the SERCA pump account for the notion that Th2 cells go through a lower level
      of lymphocyte activation compared with Th1 cells upon identical activating
      stimuli. The observed differences in calcium flux of Th1 and Th2 cells may
      contribute to different calcium handling kinetics and, hence, to distinct
      cytokine production patterns by these subsets.

PMID- 21899919
TI  - Eyelash growth in subjects treated with bimatoprost: a multicenter, randomized,
      double-masked, vehicle-controlled, parallel-group study.
AB  - BACKGROUND: Bimatoprost 0.03% is associated with increased growth and prominence
      of eyelashes. OBJECTIVE: We sought to compare the safety and efficacy of once
      daily bimatoprost 0.03% versus vehicle in increasing eyelash length, thickness,
      and darkness after topical administration to upper eyelid margins. METHODS: In
      this 5-month study, subjects were randomized to receive once-daily bimatoprost
      0.03% (n = 137) or vehicle (n = 141). The primary end point was eyelash
      prominence assessed by the investigator global eyelash assessment scale.
      Secondary efficacy measures included eyelash length, thickness, and darkness
      measured by digital image analysis and patient-reported outcomes. Safety data
      included adverse event monitoring and ophthalmic examinations. RESULTS: A higher
      percentage of subjects treated with bimatoprost 0.03% (78.1%) versus vehicle
      (18.4%) demonstrated at least a 1-grade increase in global eyelash assessment
      score at week 16 (P < .0001). Subjects in the bimatoprost 0.03% group also had
      statistically significantly greater increases in eyelash length, thickness, and
      darkness (P < .0001) than those in the vehicle group. For adverse events, only
      conjunctival hyperemia occurred at a statistically significant higher incidence
      rate in the bimatoprost 0.03% versus the vehicle group (P = .03). LIMITATIONS:
      Short-term duration of the trial was a limitation; black subjects were not
      enrolled secondary to technical requirements of digital image analysis.
      CONCLUSION: Bimatoprost 0.03% was found to be effective at enhancing eyelashes in
      adults with a very good safety profile.

PMID- 21899920
TI  - Burden of infections among 44,869 elderly in nursing homes: a cross-sectional
      cluster nationwide survey.
AB  - In France, although there are 445,000 beds in nursing homes (NHs) for elderly
      people, no studies on the burden of infections in NHs have been published. We
      sought to estimate the prevalence of infection among the residents and to assess
      the extent to which infections were associated with the residents' risk factors.
      We performed a nationwide, multicentre, cross-sectional, clustered period
      prevalence survey over five one-month periods. Cases of infection were classified
      as definite or, in the absence of laboratory confirmation, as probable. A total
      of 44,869 residents in 578 volunteer facilities were enrolled in the survey. The
      overall prevalence rate of infections was 11.23% [95% confidence interval (CI):
      10.50-11.97] and differed significantly (P<0.001) across survey periods (the time
      of the year the survey was carried out). The rate of definite cases was 4.60%
      (95% CI: 4.04-5.54) and the rate of probable cases was 6.63% (95% CI: 5.77-7.98).
      Respiratory tract infections were the most frequent and accounted for 41% of all
      infections. Infections were significantly associated with age, length of stay,
      full disability, urinary device, bedsores and the survey period. Only prevention
      programmes may reduce the impact of infections on this frail population.

PMID- 21899921
TI  - Presence of biofilm containing viable multiresistant organisms despite terminal
      cleaning on clinical surfaces in an intensive care unit.
AB  - BACKGROUND: Despite recent attention to surface cleaning and hand hygiene
      programmes, multiresistant organisms (MROs) continue to be isolated from the
      hospital environment. Biofilms, consisting of bacteria embedded in exopolymeric
      substances (EPS) are difficult to remove due to their increased resistance to
      detergents and disinfectants, and periodically release free-swimming planktonic
      bacteria back into the environment which may may act as an infection source. AIM:
      To establish whether reservoirs of MROs exist in the environment as biofilms.
      METHODS: Following terminal cleaning, equipment and furnishings were removed
      aseptically from an intensive care unit (ICU) and subjected to culture and
      scanning electron microscopy (SEM). Samples were placed in 5 mL of tryptone soya
      broth, sonicated for 5 min before plate culture on horse blood agar, Brillance
      MRSA and Brilliance VRE agar plates. Samples for SEM were fixed in 3%
      glutaraldehyde and hexamethyldisilizane (HMDS) prior to sputter-coating with gold
      and examination in an electron microscope. FINDINGS: Biofilm was demonstrated
      visually on the sterile supply bucket, the opaque plastic door, the venetian
      blind cord, and the sink rubber, whereas EPS alone was seen on the curtain.
      Viable bacteria were grown from three samples, including MRSA from the venetian
      blind cord and the curtain. CONCLUSION: Biofilm containing MROs persist on
      clinical surfaces from an ICU despite terminal cleaning, suggesting that current
      cleaning practices are inadequate to control biofilm development. The presence of
      MROs being protected within these biofilms may be the mechanism by which MROs
      persist within the hospital environment.

PMID- 21899922
TI  - Cluster of non-tuberculous mycobacteraemia associated with water supply in a
      haemato-oncology unit.
AB  - Non-tuberculous mycobacteria (NTM) are ubiquitous environmental organisms but
      rarely cause infections. Clinical, microbiological and epidemiological
      investigations and subsequent management of a cluster of NTM bacteraemia on a
      haemato-oncology unit are reported. From October 2007 to July 2008, five patients
      being managed for haematological malignancies developed pyrexia and general
      malaise. Mycobacterium mucogenicum (four patients) and Mycobacterium neoaurum
      (one patient) were identified from their blood cultures. The environment, in
      particular the water system, was investigated to identify the source of the
      infection and multiple water samples were cultured according to established
      criteria. NTM were also isolated from the hospital water system. Central venous
      catheters (CVCs) were removed and the patients were successfully treated with
      antibiotics. Environmental measures and changes in CVC care were introduced to
      prevent further episodes of NTM bacteraemia in these patients. Despite these
      measures, NTM continued to be present in the water system, but new clinical cases
      were not identified. NTM are common environmental organisms and are recognized as
      being difficult to remove from water systems. CVCs were presumed to be the portal
      of entry in this cluster of NTM bacteraemia, and the implementation of changes to
      CVC care protocols was successful in preventing further infections in this
      immunocompromised patient group.

PMID- 21899923
TI  - Surgical site infection after central venous catheter-related infection in
      cardiac surgery. Analysis of a cohort of 7557 patients.
AB  - The aim of this study was to establish the relationship between the occurrence of
      a surgical site infection (SSI) and the presence of a central venous catheter
      related infection (CVCRI). The Department of Thoracic and Cardiovascular Surgery,
      University Hospital, Rouen, has carried out a prospective epidemiological survey
      of all nosocomial infections (pneumonia, SSI and CVCRI) since 1997. The study
      group included all consecutive patients who underwent cardiac surgery over a 10
      year period from 1997 to 2007. A nested case-control study was conducted to
      identify the risk factors for SSI after CVCRI. Cases were patients with SSI after
      CVCRI and controls were randomized from patients who presented with CVCRI not
      followed by SSI. In total, 7557 patients were included and 133 SSIs (1.7%) were
      identified. The rate of superficial SSI was 0.7% [95% confidence interval (CI):
      0.5-0.9] and of mediastinitis was 1.0% (95% CI: 0.8-1.2). Among the 133 cases of
      SSI, 12 (9.0%; 95% CI: 5.0-14.8) occurred after a CVCRI with identical micro
      organisms. CVCRI [adjusted odds ratio (aOR): 5.2; 95% CI: 3.2-8.5], coronary
      artery bypass grafting (aOR: 2.9; 95% CI: 1.6-5.2), and obesity (aOR: 11.4; 95%
      CI: 1.0-130.1) were independent factors associated with SSI. The new finding of
      this study is that patients with CVCRI were 5.2 times more likely to develop SSI
      compared to patients without CVCRI.

PMID- 21899924
TI  - Parathyroid hormone early percent change: an individualized approach to predict
      postthyroidectomy hypocalcemia.
AB  - PURPOSE: The purpose of this study is to evaluate a percent change model of
      postoperative parathyroid hormone level in thyroidectomy patients as a predictor
      of hypocalcemia. MATERIALS AND METHODS: Chart review was completed on patients
      who had undergone total or completion thyroidectomy over a 22-month period in our
      department. Only those patients with a preoperative ionized calcium and
      parathyroid hormone (PTH) level and at least 1 postoperative result were
      included. Ionized calcium levels served as an internal control. The Student t
      test was used to compare PTH level between the normocalcemic and hypocalcemic
      groups at each time point. Logistic regression analysis was used to predict
      hypocalcemia based on the diagnostic criteria. Receiver operator curves were used
      to maximize sensitivity. RESULTS: Fifty-two patients met the inclusion criteria
      during the study period. A total of 22 patients (42%) experienced hypocalcemia.
      We were unable to maximize both sensitivity and specificity at the same time
      point. When comparing preoperative to 6-hour postoperative PTH percent change,
      patients with a greater than 44% decrease are likely to have hypocalcemia, with a
      sensitivity of 100%. Likewise, in those patients without a greater than 44%
      decrease at 6 hours, early discharge can be considered safe, given the negative
      predictive value of 100%. CONCLUSION: In our series, patients with a greater than
      44% PTH decrease from preoperative to 6-hour postoperative are very likely to
      develop hypocalcemia. We would propose that these patients need further inpatient
      monitoring to progress to safe discharge. Likewise, patients with a less than 44%
      decrease at the 6-hour time point are unlikely to develop hypocalcemia and may be
      considered safe for discharge.

PMID- 21899925
TI  - [Influence of diurnal variation in the size of acute myocardial infarction].
AB  - OBJECTIVE: To evaluate whether the size of acute myocardial infarction (AMI)
      shows circadian variability. DESIGN: An observational, prospective study.
      SETTING: A 12-bed coronary care unit. PATIENTS: Consecutive patients diagnosed
      with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous
      coronary intervention. INTERVENTIONS: The patients were divided into two groups
      according to the time of onset of AMI symptoms (Group A: 0-12hours, Group B: 12
      24hours). MAIN VARIABLES OF INTEREST: Age, sex, cardiovascular risk factors,
      coronary anatomy, left ventricular ejection fraction, infarct location, time from
      onset of symptoms to reperfusion, presence of heart failure upon admission, and
      peak troponin I value. RESULTS: A total of 108 patients with a diagnosis of STEMI
      were included. Patients in group A showed a higher troponin I concentration
      compared to group B (troponin I: 70.85+/-16.38 versus 60.90+/-22.92ng / ml,
      p=0.003). In the multivariate analysis the onset of AMI between 0-12hours was
      identified as an independent predictor of infarct size (OR: 1.133, 95%CI 1.012
      1.267, p=0.01). CONCLUSIONS: An onset of AMI between 0-12hours results in a
      significantly larger final size of necrosis compared with any other time of
      presentation.

PMID- 21899926
TI  - [Bilateral hip osteonecrosis following refractory septic shock].

PMID- 21899928
TI  - Variation in biofilm formation among blood and oral isolates of Candida albicans
      and Candida dubliniensis.
AB  - INTRODUCTION: Biofilm production is considered a potential virulence factor of
      some Candida species. For this reason, an understanding of biofilm behavior of
      Candida albicans and its closely related species Candida dubliniensis is key to
      the development of effective preventive measures for invasive and oral
      candidiasis. The aim of this study was to compare the capacity of biofilm
      production by blood and oral isolates of C. albicans and C. dubliniensis using
      polystyrene, flat-bottomed 100-well microtiter plates. METHODS: A total of 47
      isolates, consisting of 28 C. albicans (16 oral and 12 blood isolates) and 19 C.
      dubliniensis (11 oral and 8 blood isolates) were compared for their biofilm
      forming ability under aerobic and static conditions. XTT reduction assay was used
      to quantify the sessile growth. RESULTS: All tested isolates produced biofilm,
      measured as XTT metabolic activity. Biofilm formation by C. albicans isolates was
      statistically significantly higher than biofilm formation by C. dubliniensis
      isolates at 24h (P=0.03) and 48 h (P=0.0001). There was a higher percentage
      (41.7%) of high producers of biofilms among C. albicans blood isolates than among
      oral isolates (31.3%), without statistically significant differences.
      CONCLUSIONS: This capability may allow C. albicans and C. dubliniensis to
      maintain their oral ecological niches as commensal or pathogenic microorganisms
      and can be a major virulence factor during invasive candidiasis. However, the
      differences in biofilm production among isolates should be taken into account
      when the anti-biofilm activity of antifungal agents or other virulence factors
      are tested in vitro.

PMID- 21899929
TI  - Synthesis and biological evaluation of dihydroindeno and indeno [1,2-e]
      [1,2,4]triazolo [3,4-b] [1,3,4]thiadiazines as antimicrobial agents.
AB  - Two series of compounds namely, dihydroindeno and indeno [1,2-e] [1,2,4]triazolo
      [3,4-b] [1,3,4]thiadizines (9a-l & 11a-l) were synthesized by cyclocondensation
      between alpha-bromoindanones (7a-b) or/and alpha,alpha-dibromoindanones (8a-b)
      and various 3-alkyl/aryl-4-amino-5-mercapto-1,2,4-s-triazoles (3a-f) in methanol
      with an aim to explore their effect on in vitro growth of microorganism causing
      microbial infection. In vitro antibacterial activity was performed against four
      strains namely, Staphylococcus aureus, Bacillus subtilis, Escherichia coli,
      Pseudomonas aeruginosa and antifungal activity against three fungal strains
      namely, Aspergillus niger, Aspergillus flavus, Penicillium species. Of all the
      compounds screened for activity some of the compounds were associated with
      considerably higher antibacterial and antifungal activity than commercial
      antibiotics.

PMID- 21899930
TI  - Monoamine oxidase inhibition by selected anilide derivatives.
AB  - A series of anilide derivatives were synthesized and evaluated as inhibitors of
      recombinant human monoamine oxidase (MAO) A and B. The most potent inhibitors
      among the derivatives that were initially evaluated were (2E)-N-(3-chlorophenyl)
      3-phenylprop-2-enamide (2c) and (2E)-N-(3-bromophenyl)-3-phenylprop-2-enamide
      (2d) with IC(50) values of 0.53 MUM and 0.45 MUM, respectively. These derivatives
      exhibited reversible and selective inhibition of MAO-B with binding affinities 37
      fold higher for MAO-B than for MAO-A. Analysis of the possible binding
      interactions of these inhibitors with active site models of human MAO-A and -B
      led to the design of phenolic and benzonitrile derivatives of 2c and 2d. Among
      these were (2E)-N-(3-chlorophenyl)-3-(4-hydroxyphenyl)prop-2-enamide (7c) and
      (2E)-N-(3-bromophenyl)-3-(4-hydroxyphenyl)prop-2-enamide (7d) which inhibited MAO
      B selectively and reversibly with IC(50) values of 0.032 MUM and 0.026 MUM,
      respectively. These inhibitors were at least 14 fold more potent than 2c and 2d.
      This study concludes that N,3-diphenylprop-2-enamide is a suitable scaffold for
      the design of selective MAO-B inhibitors and structural modifications to enhance
      the binding affinities of the inhibitors for the MAO-B active site include
      substitution with halogens on the N-phenyl ring and substitution with hydroxyl
      and nitrile functional groups on the para and meta positions, respectively, of
      the C3 phenyl ring. Possible binding modes of these structures within the MAO-B
      active site are proposed with the emphasis on the interactions of the inhibitor
      halogens and the hydroxyl and nitrile functional groups with active site residues
      and water molecules.

PMID- 21899931
TI  - Synthesis and pharmacological evaluation of indole-based sigma receptor ligands.
AB  - A series of novel indole-based analogs were prepared and their affinities for
      sigma receptors were determined using in vitro radioligand binding assays. The
      results of this study identified several compounds with nanomolar sigma-2
      affinity and significant selectivity over sigma-1 receptors. In particular, 2-(4
      (3-(4-fluorophenyl)indol-1-yl)butyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
      (9f) was found to display high affinity at sigma-2 receptors with good
      selectivity (sigma-1/sigma-2 = 395). The pharmacological binding profile for this
      compound was established with other relevant non-sigma sites.

PMID- 21899932
TI  - Increased Vitamin B12 levels are associated with mortality in critically ill
      medical patients.
AB  - BACKGROUND & AIMS: We describe an observational study in critically ill medical
      patients showing the association between serum Vitamin B12 levels measured on or
      near admission and the outcome in these patients. METHODS: We used the database
      of patients admitted to the Medical Intensive Care Unit (MICU) at the Hadassah
      Hebrew University Medical Center in Jerusalem, Israel, to analyze associations
      between patient demographics, background, diagnoses and serum Vitamin B12 levels
      with hospital and 90 day outcomes. RESULTS: Higher mean Vitamin B12 levels were
      found in patients who did not survive their hospital stay (1719 pg/ml vs 1003
      pg/ml, p < 0.01). Those who had died by 90 days after admission to the MICU also
      had higher Vitamin B12 levels than survivors (1593 pg/ml vs 990 pg/ml).
      Regression analysis showed that elevated Vitamin B12 levels were associated with
      increased 90 day mortality, even after controlling for other variables. Survival
      analysis also showed an increased mortality rate in patients with Vitamin B12
      levels over 900 pg/ml (p < 0.0002). CONCLUSIONS: Our data show that high serum
      Vitamin B12 levels are associated with increased mortality in critically ill
      medical patients. We suggest that Vitamin B12 levels should be included in the
      work-up of all medical intensive care patients, particularly those with a chronic
      health history and increased severity of illness.

PMID- 21899933
TI  - Increased power generation in impaired lower extremities correlated with changes
      in walking speeds in sub-acute stroke patients.
AB  - BACKGROUND: Establishing changes in net joint power in the lower extremity of
      patients during recovery of walking might direct gait training in early stroke
      rehabilitation. It is hypothesized that (1) net joint power in the lower
      extremity joints would increase in sub-acute stroke patients following gait
      rehabilitation, and (2) the improvements in net joint power would be
      significantly correlated with changes in walking speed. METHODS: Thirteen sub
      acute patients (<3 months from stroke onset) participated in the study. All
      patients completed 6 weeks of gait training (3 weeks of robotic gait training and
      3 weeks of physiotherapy). The gait patterns were analyzed using 3D motion
      analysis before and after training. The assessed variables were; gait speed and
      the net peak joint power of the ankle plantar flexors, hip extensors, hip
      flexors, hip abductors, and knee extensors. FINDINGS: Ankle plantar flexor power
      in the impaired limb and hip extensor power in the unimpaired limb increased
      significantly following training (133% and 77%, respectively; P<0.002).
      Improvements (from 20% to 133%) in net joint power of the ankle plantar flexors,
      hip extensors, hip flexors, and hip abductors of the impaired limb and ankle
      plantar flexors and hip abductors of the unimpaired limb significantly correlated
      with the recovery of walking speed following training (0.24 m/s to 0.51 m/s)
      (r=0.71-0.86). INTERPRETATION: The findings suggested investigations for
      strengthening the plantar flexors, hip flexors, hip extensors, and hip abductors
      concentrically, and knee extensors eccentrically in the impaired limb to
      determine the effectiveness in improving gait performance.

PMID- 21899934
TI  - Effect of lower limb dominance on knee joint kinematics after anterior cruciate
      ligament reconstruction.
AB  - BACKGROUND: Normal ambulatory kinematics of the knee joint is often not fully
      restored after anterior cruciate ligament reconstruction, which may increase the
      risk for cartilage degeneration and premature osteoarthritis in the involved
      knees. Lower limb dominance may have impacts on knee joint kinematics after
      anterior cruciate ligament reconstruction, which may lead to a different
      prevalence of cartilage degeneration. This study aimed to evaluate the knee joint
      kinematics among patients with reconstruction on the dominant and non-dominant
      side. METHODS: Forty-one subjects with unilateral anterior cruciate ligament
      reconstruction (19 dominant, 22 non-dominant) were recruited after being
      discharged from rehabilitation programs. Twenty healthy subjects were recruited
      as the control group. Six degrees-of-freedom tibiofemoral motion during level
      walking was determined using a redundant point cluster-based marker set.
      Tibiofemoral joint motion and its bilateral differences were compared within each
      group and between groups. FINDINGS: The non-dominant reconstructed knees had less
      extension compared to their contralateral knees at heel strike and during middle
      stance phase (P=0.02); whereas, the dominant reconstructed knees exhibited
      significantly reduced varus rotation (-2.1 degrees  on mean, P=0.027) and
      internal tibial rotation (P=0.034) compared to their contralateral knees during
      both stance and swing phases. INTERPRETATION: The results show that different
      kinematics has been developed between the involved dominant and non-dominant
      knees after anterior cruciate ligament reconstruction, especially the secondary
      rotations. The differences are consistent with the unequal prevalence of
      cartilage degeneration in the knee joint. The findings demonstrated that the
      lower limb dominance had a significant effect on post-surgery knee kinematics.

PMID- 21899935
TI  - Concentrations and assessment of exposure to siloxanes and synthetic musks in
      personal care products from China.
AB  - We investigated the concentrations and profiles of 15 siloxanes (four cyclic
      siloxanes, D(4)-D(7); 11 linear siloxanes, L(4)-L(14)), four synthetic musks (two
      polycyclic musks, HHCB and AHTN; two nitro musks, MX and MK), and HHCB-lactone,
      in 158 personal care products marketed in China. Siloxanes were detected in 88%
      of the samples analyzed, at concentrations as high as 52.6 mg g(-1); Linear
      siloxanes were the predominant compounds. Among synthetic musks, more than 80% of
      the samples contained at least one of these compounds, and their total
      concentrations were as high as 1.02 mg g(-1). HHCB was the predominant musk in
      all of the samples analyzed, on average, accounting for 52% of the total musk
      concentrations. Based on the median concentrations of siloxanes and musks and the
      average daily usage amounts of consumer products, dermal exposure rates in adults
      were calculated to be 3.69 and 3.38 mg d(-1) for siloxanes and musks,
      respectively.

PMID- 21899936
TI  - Biogeochemical dynamics of perfluorinated alkyl acids and sulfonates in the River
      Seine (Paris, France) under contrasting hydrological conditions.
AB  - The biogeochemical dynamics of 15 perfluorinated compounds (PFCs) were
      investigated in a heavily urbanised river (River Seine, Paris, France). The
      target compounds included C4-C10 sulfonates and C5-C14 acids; eleven PFCs were
      detected and ?PFCs ranged between 31 and 91 ng L(-1) (median: 47 ng L(-1)). The
      molecular pattern was dominated by the perfluoroalkyl sulfonates PFHxS and PFOS
      (>54% of ?PFCs), which were the only PFCs quantified in both the dissolved and
      particulate phases. For these PFCs, the sorbed fraction positively correlated
      with suspended sediment levels. Total PFC levels negatively correlated with river
      flow rate, which varied between 150 and 640 m(3) s(-1). This suggests the
      predominance of point sources (likely WWTP effluent discharge), but a
      contribution of non-point sources such as combined sewer overflow could not be
      excluded. The annual PFC mass flow was estimated at 500 kg, which is less than
      observed for other large European rivers.

PMID- 21899937
TI  - The oxidative potential and biological effects induced by PM10 obtained in Mexico
      City and at a receptor site during the MILAGRO Campaign.
AB  - As part of a field campaign that studied the impact of Mexico City pollution
      plume at the local, sub-regional and regional levels, we studied transport
      related changes in PM(10) composition, oxidative potential and in vitro
      toxicological patterns (hemolysis, DNA degradation). We collected PM(10) in
      Mexico City (T(0)) and at a suburban-receptor site (T(1)), pooled according to
      two observed ventilation patterns (T(0) -> T(1) influence and non-influence).
      T(0) samples contained more Cu, Zn, and carbon whereas; T(1) samples contained
      more of Al, Si, P, S, and K (p < 0.05). Only SO(4)(-2) increased in T(1) during
      the influence periods. Oxidative potential correlated with Cu/Zn content (r =
      0.74; p < 0.05) but not with biological effects. T(1) PM(10) induced greater
      hemolysis and T(0) PM(10) induced greater DNA degradation. Influence/non
      influence did not affect oxidative potential nor biological effects. Results
      indicate that ventilation patterns had little effect on intrinsic PM(10)
      composition and toxicological potential, which suggests a significant involvement
      of local sources.

PMID- 21899938
TI  - "But then i learned...": weight loss surgery patients negotiate surgery
      discourses.
AB  - This research explores commonplace discursive depictions of obesity surgery and
      individual patients' reactions to these depictions. Data come from a content
      analysis of weight loss surgery representations in periodical articles (n = 32)
      and open-ended surveys (n = 55) and interviews (n = 44) with surgery patients
      from 34 US states. This study reveals that mainstream periodicals frequently
      stigmatized patients as obesity surgery is cast as (1) medically risky, (2)
      extravagant and (3) an overly easy escape from obesity. Surgery is only portrayed
      as (4) acceptable when multiple other weight loss techniques had been tried
      unsuccessfully. In contrast, interview and survey data show individual patients
      are aware of, yet frequently refute, these surgical stigmas. Findings demonstrate
      the importance of weight loss surgery patients' personal experiences,
      interactions and education in shaping their responses to stigma. Patients view
      themselves as expert insiders who negotiate dominant discourses and,
      consequently, assert that surgery and surgery patients are ethical. Research
      results reveal the importance of perceived expert insider status and interpretive
      practice in managing obesity surgery stigma.

PMID- 21899939
TI  - [Lateral Intercostal Artery Perforator (LICAP) flap for lateral breast defect
      reconstruction].
AB  - Lateral breast defect after partial mastectomy is a difficult challenge. Pedicled
      perforator flap is a new indication for breast surgery. Perforator flaps and fat
      tissue transplant are new concepts in this kind of reconstruction. Lateral
      intercostal artery perforator (LICAP) flap has been used for a lot of
      indications. It can be used for lateral breast defect reconstruction. This flap
      provides several advantages: minimal donor site morbidity, advantages in flap
      shaping, better aesthetic results and higher patient satisfaction. The aim of
      this paper is to present indications of LICAP flap. We discuss its advantages and
      its limits in lateral breast reconstruction after partial mastectomy. LICAP flap
      provides a new solution instead of conventional flaps.

PMID- 21899940
TI  - [Macrolane(r): A severe case of calf cellulitis after modeling injection].
AB  - In recent years, the market for resorbable injectables has been steadily
      expanding. The European Community's seal of approval (CE) is a sufficient
      guaranty to get them distributed. These injectables do not require official
      approval because they are considered to be "implantable medical devices" and not
      medicines. Macrolane((r))is a hyaluronic acid in gel form (NASHA [non-animal
      stabilized hyaluronic acid]) and has been on the French market since 2007. It can
      be injected into all areas except the face. It is highly cross-linked which,
      while slowing its absorption into the body, can also leave long-lasting residues.
      We report the first case of cellulitis after injection into the calf by a
      practitioner in his office.

PMID- 21899941
TI  - [Surgical strategy for neck burns and their sequelae].
AB  - Burns of the neck are common and expose them to functional and aesthetic
      complications which are sometimes very serious. Care in the acute stage and
      treatment of sequelae contribute to a common goal of restoration: Maintain or
      recreate a chin-neck angle and get a quality skin as close as possible to the
      original skin, in terms of flexibility, texture, thickness and color. The wide
      variety of cases encountered requires knowing the armamentarium available to us
      today, and the anatomical basis and clinical underlying indications.

PMID- 21899942
TI  - Type I leucocyte adhesion deficiency (LAD I). Report of a case.

PMID- 21899943
TI  - Cardiotocography as a predictor of fetal outcome in women presenting with reduced
      fetal movement.
AB  - OBJECTIVE: To examine the obstetric and perinatal outcomes of women presenting
      with reduced fetal movement (RFM) during the third trimester, specifically in
      relation to the diagnostic capacity of non-stress cardiotocography (CTG) used as
      the primary investigation in this clinical scenario. STUDY DESIGN: This was a
      retrospective population-based cohort study of pregnancy outcomes of all women >=
      28 weeks' gestation with singleton pregnancies presenting during one calendar
      year with maternal perception of RFM, all of whom underwent CTG at presentation.
      Main outcome measures included: obstetric intervention (induction of labour,
      spontaneous vaginal delivery, operative vaginal delivery, emergency caesarean
      section), and perinatal outcome (subsequent perinatal death, low Apgar scores
      (<7(5)), neonatal resuscitation and NICU admission). RESULTS: In all, 524 women
      presented with RFM and a live fetus, representing 7% of the antenatal obstetric
      population; 284 women (54%) were nulliparous. The reassuring CTG group comprised
      482 (92%) women in whom initial CTG was reassuring and 15 (3%) where a repeat
      tracing within 1h was reassuring. The non-reassuring/abnormal CTG group (n=27,
      5%) either underwent emergency delivery or comprehensive serial fetal assessment;
      this group had significantly higher rates of emergency caesarean delivery,
      neonatal resuscitation and NICU admission; the incidence of small-for-gestational
      age infants did not differ significantly. No perinatal death occurred in either
      group following CTG. CONCLUSION: Normal non-stress CTG is a reliable screening
      indicator of fetal wellbeing in women presenting with perception of RFM in the
      third trimester; abnormal pregnancy outcomes were more common when initial CTG
      was abnormal or persistently non-reassuring.

PMID- 21899944
TI  - Re: Jurgen Pannek. Mozart, the brain, and the bladder: clinical usefulness of
      near-infrared spectroscopy for the detection of detrusor overactivity. Eur Urol
      2011;59:763-4.

PMID- 21899945
TI  - The anti-progestin RU-486 inhibits viability of MCF-7 breast cancer cells by
      suppressing WNT1.
AB  - The Wnt signaling pathway is activated in over 50% of women with breast cancer
      and contributes to tumor progression. Here, we investigated the effects of RU-486
      on Wnt signaling in breast cancer cell lines. RU-486 reduced viability of the
      progesterone receptor-positive MCF-7 and T-47D cells, but had no effect on the
      triple-negative MDA-MB-231 cells. Furthermore, RU-486 suppressed WNT1 expression
      of MCF-7 cells by 99%. The addition of recombinant WNT1 partially reversed the RU
      486-dependent inhibition of viability in MCF-7, but not in T-47D cells. In
      conclusion, we identified WNT1 as a novel mediator of the anti-tumor effects of
      RU-486 in MCF-7 cells.

PMID- 21899946
TI  - Nitroxoline (8-hydroxy-5-nitroquinoline) is more a potent anti-cancer agent than
      clioquinol (5-chloro-7-iodo-8-quinoline).
AB  - Clioquinol has been shown to have anticancer activity both in vitro and in vivo.
      The present study compared the cytotoxicity of clioquinol with six analogues
      using human cancer cell lines. Of the analogues tested, 8-hydroxy-5
      nitroquinoline (NQ) was the most toxic, with an IC(50) that was five to ten fold
      lower than that of other congeners. Its activity was enhanced by copper, but not
      zinc, and the use of a zinc-sensitive fluorophore showed that unlike clioquinol,
      NQ is not a zinc ionophore. NQ increased intracellular reactive oxygen species
      generation, an effect that was significantly enhanced by the addition of copper
      at levels approximately the same as those found in human plasma. NQ has been used
      in humans for the treatment of urinary infections. NQ is an 8-hydroxyquinoline
      derivative that is more potent than the halogenated 8-hydroxyquinolines, and it
      may be less neurotoxic because it lacks zinc ionophore activity. NQ is another
      clinically used anti-microbial agent whose properties suggest that it may be
      useful in treating cancer.

PMID- 21899947
TI  - Glycosylation-related gene expression is linked to differentiation status in
      glioblastomas undifferentiated cells.
AB  - Glioblastoma Multiforme (GBM) is the most frequent malignant brain tumor with
      still poor prognosis. Tumor initiation, growth and recurrences might depend on
      Brain Tumor Stem Cells (BTSCs) which can promote tumor aggressiveness and
      potentially affords new therapeutic target. Recent works emphasized aberrant cell
      surface glyco-conjugate expression in brain tumors suggesting that altered
      glycosylation is closely linked to cancer tumor metastasis and invasive process.
      Post-translational changes might play a key role in determining the fates of most
      aggressive and undifferentiated cells such as self-renewal, proliferation and
      differentiation. In order to characterize the glycosylation-related genes
      involved in differentiation status of the BTSCs, two glioblastoma cell lines, U87
      MG and U251 have been cultured according to two conditions leading to
      undifferentiated floating cells or differentiated adherent cells. The expression
      level of 559 glycosylation related genes has been analyzed by Taqman Low Density
      Array (TLDA) analysis and allowed to isolate eight up-regulated genes specific of
      a subpopulation of undifferentiated cells. Protein expression has been confirmed.
      Among main selected genes, five are also over-expressed in the undifferentiated
      condition in primary cultures provided by three GBM freshly isolated from
      patient. This work suggests that new Glycosylation-related gene signature might
      improve the characterization of the most aggressive and undifferentiated cells
      and supports that in future, N-linked glycosylation might provide new target to
      develop therapeutic strategy for inhibiting tumor growth.

PMID- 21899948
TI  - Responses of Scirpus triqueter, soil enzymes and microbial community during
      phytoremediation of pyrene contaminated soil in simulated wetland.
AB  - The aim of this study was to determine the enhancement of Scirpus triqueter in
      the dissipation of pyrene and the interaction of pyrene with plant, soil enzymes
      and microbial community. The results indicated that the dissipation ratios of
      pyrene in the rhizospheric and non-rhizospheric soil were 64.65 +/- 3.86% and
      54.49 +/- 2.74%, respectively, and were higher than that in the unplanted soil
      (42.60 +/- 0.71%) at 80 d after planting S. triqueter. The pyrene was toxic to S.
      triqueter, as evidenced by growth inhibition in height, diameter, shoot number
      and biomass during the planting period. The activities of dehydrogenase decreased
      significantly at the presence of pyrene in soils, and increased remarkably with
      the introduction of S. triqueter. It was found that the pyrene addition increased
      the ratios of fungal/total fatty acids and gram-positive/gram-negative, but the
      presence of S. triqueter decreased the ratios of gram-positive/gram-negative. A
      larger stress level was found in the pyrene treated soils without S. triqueter.
      The ratio of aerobic/anaerobic bacteria decreased with increasing pyrene
      concentration, but increased when S. triqueter was planted. The principal
      analysis of phospholipid fatty acid signatures revealed that microbial community
      structures in the rhizospheric and non-rhizospheric soil were similar, but
      different from those in the unplanted and control soil.

PMID- 21899950
TI  - A zero waste vision for industrial networks in Europe.
AB  - 'ZeroWIN' (Towards Zero Waste in Industrial Networks--www.zerowin.eu) is a five
      year project running 2009-2014, funded by the EC under the 7th Framework
      Programme. Project ZeroWIN envisions industrial networks that have eliminated the
      wasteful consumption of resources. Zero waste is a unifying concept for a range
      of measures aimed at eliminating waste and challenging old ways of thinking.
      Aiming for zero waste will mean viewing waste as a potential resource with value
      to be realised, rather than as a problem to be dealt with. The ZeroWIN project
      will investigate and demonstrate how existing approaches and tools can be
      improved and combined to best effect in an industrial network, and how innovative
      technologies can contribute to achieving the zero waste vision.

PMID- 21899949
TI  - Synthesis and adsorption properties of titanosilicates ETS-4 and ETS-10 from fly
      ash.
AB  - ETS-4 and ETS-10 titanosilicates were prepared from fly ash and anatase, as
      silica and titanium sources respectively, via a hydrothermal procedure for the
      first time. The fusion of fly ash by alkali was carried out at a relatively low
      temperature and the use potassium fluoride salt was avoided in the synthesis of
      ETS. The by-product of this process is mainly NaCl, which is a useful source
      material for industry. The energy efficiency and yield of the synthesis process
      was improved by directly recycling the final filtrate after recovering the
      product viz ETS-4. All the ETS materials were characterized in terms of
      structural morphology, thermal stability and surface/pore properties. The
      properties of ETS-4 prepared from fly ash by the filtrate recycling method were
      comparable to that from commercial sources. The results show that ETS type
      materials can be prepared from cheaper resources, with good purity, comparable
      physico-chemical properties as well as excellent adsorption properties with lower
      environmental impact.

PMID- 21899951
TI  - Characterization of chars produced in the co-pyrolysis of different wastes:
      decontamination study.
AB  - The present work is devoted to the study of the decontamination of chars obtained
      in the co-pyrolysis of plastics, biomass and tyre wastes. The chars were
      extracted with several organic solvents of different polarities either
      individually or in sequence. The ability of each selected extractant to remove
      toxic pollutants was evaluated by comparing the extraction yields and by
      characterizing the crude extracts with a combination of chemical analysis and
      toxicity bioassays. Also, the mineral composition of the treated and non-treated
      chars was assessed. The results obtained in this study indicate that hexane is
      the more efficient extraction solvent to be used in the organic decontamination
      of chars obtained in the co-pyrolysis of plastics, tyres and biomass. A
      sequential extraction with solvents of increasing polarity can provide a better
      decontamination of the raw pyrolysis char than any individual extraction. The
      compounds removed from the char during the decontamination process are mainly
      aliphatic hydrocarbons and aromatic hydrocarbons, therefore a material that may
      be upgraded to be used as a fuel and/or as raw material for the organic chemical
      industry.

PMID- 21899952
TI  - Prevalence and risk factors of Giardia duodenalis in dogs from Romania.
AB  - The protozoan Giardia duodenalis is a mammalian-infecting parasite that produces
      diarrhoea and malabsorption in its hosts. A survey to investigate canine
      infections with G. duodenalis in Romania was undertaken between June 2008 and
      December 2009. The objectives of the study were to (i) estimate the prevalence of
      infection in different dog populations (kennels, shelters, shepherd, household)
      using microscopy and a commercially available enzyme-linked immunosorbent assay
      (ELISA) test kit; (ii) to establish the level of agreement and characteristics of
      the tests; and (iii) to identify risk factors for infection by multivariate
      logistic regression models. Faecal samples were collected from 614 dogs aged from
      1 month to 16 years (mean +/- SD=2.88 +/- 2.86 years). Each sample was tested for
      the presence of cysts using a flotation method with saturated sodium chloride
      solution and 416 out of 614 stool samples were further examined for the presence
      of G. duodenalis specific antigens using Giardia Microwell ELISA (SafePathTM
      Laboratories). Giardia cysts were identified in 8.5% of total dogs (52/614) and
      statistical significantly more frequently in dogs living in communities. The
      cysts prevalence according with dog populations was as follows: 7.2%(9/125) in
      kennel dogs; 16.5%(27/164 in shelter dogs; 4.3%(2/46) in shepherd dogs;
      4.8%(4/84) in household dogs from urban areas; and 5.1%(10/195) in household dogs
      from rural areas. The overall prevalence of Giardia infection by ELISA was 34.6%
      (144/416). The prevalence was significantly higher in kennel dogs (50%; 13/26),
      shelter dogs (47.7%; 74/155) and shepherd dogs (40.5%; 17/42) than in household
      dogs from urban areas (34.1%; 15/44) and household dogs from rural areas (16.8%;
      25/149). It was noticed poor agreement between microscopy and ELISA (k=0.19). The
      microscopy performed best, with an Youden Index of 0.74, a Se of 73.68% and a Sp
      of 100%. ELISA had 100% Sp, but only 19.44% Se. Young dogs (up to 12 months age)
      and living in communities were identified as risk factors for infection by
      multivariate logistic regression analysis. 71.2% (37/52) Giardia cysts positive
      dogs presented co-infections with other intestinal parasites: Toxocara canis
      (14/52; 26.9%), Isospora ohioensis (12/52; 23.1%), Ancylostoma caninum (9/52;
      17.3%), Uncinaria stenocephala (7/52; 13.5%), Trichocephalus vulpis (6/52;
      11.5%), Hammondia heydorni/Neospora caninum (5/52; 9.6%), Sarcocystis spp. (5/52;
      9.6%), Isospora canis (4/52; 7.7%), Capillaria aerophila (3/52; 5.8%),
      Strongyloides stercoralis (2/52; 93.8%), Dipylidium caninum (1/52; 1.9%) and
      Toxascaris leonina (1/52; 1.9%).

PMID- 21899953
TI  - Insecticidal and repellent effects of tea tree (Melaleuca alternifolia) oil
      against Lucilia cuprina.
AB  - Laboratory studies were conducted to assess the effect of tea tree oil (TTO) from
      Melaleuca alternifolia (terpinen-4-ol chemotype) against different stages of the
      Australian sheep blowfly Lucilia cuprina. When applied to wool, 3% TTO
      formulation repelled gravid female L. cuprina and prevented oviposition for six
      weeks. Formulations containing 1% TTO caused 100% mortality of L. cuprina eggs
      and 1st instar larvae and 2.5% TTO caused mortality of most second and third
      instar larvae in agar feeding assays. In experiments where third instar larvae
      were dipped in TTO formulations for 60s, concentrations of up to 50% TTO gave
      less than 50% kill. TTO at concentrations of 0.5%, 2% and 5% was strongly
      repellent to third instar larvae and caused them to evacuate treated areas.
      Inclusion of TTO in formulations with diazinon, ivermectin and boric acid reduced
      mortality in comparison with the larvicides used alone, at least partially
      because of avoidance behaviour stimulated by the TTO. Addition of TTO to wound
      treatments may aid in wound protection and myiasis resolution by preventing
      oviposition by L. cuprina adults, insecticidal action against L. cuprina eggs and
      larvae, stimulating larvae to leave the wound and through antimicrobial and anti
      inflammatory properties that aid in wound healing.

PMID- 21899954
TI  - Apoptosis in T lymphocytes from spleen tissue and peripheral blood of L. (L.)
      chagasi naturally infected dogs.
AB  - Dogs are the main domestic reservoirs of L. (L.) chagasi. Once in the vertebrate
      host, the parasite may cause visceral leishmaniasis, which can also be
      transmitted to humans. Infected symptomatic dogs show disorganization in the
      white pulp in spleen tissue and a reduction in T lymphocytes in peripheral blood.
      To investigate whether apoptosis is involved in white pulp disorganization and
      diminished T cell counts in peripheral blood, apoptotic T cells from the spleen
      and peripheral blood of dogs naturally infected with L. (L.) chagasi and
      presenting clinical manifestations were quantified and compared with healthy
      dogs. Thirteen symptomatic adult dogs infected by L. (L.) chagasi and six healthy
      dogs from a nonendemic area (controls) were included in the study. Samples from
      spleen and peripheral blood were used to quantify apoptosis in CD3 lymphocytes by
      flow cytometry using Anexin V and Multicaspase kits; the results were compared
      using the Mann Whitney test. The percentage of total T cells was lower in
      Leishmania infected dogs compared to healthy controls (P<0.05). Apoptosis levels
      in T cells from PBMC and spleen were higher in infected dogs than in controls
      (P<0.05). The least squares method test was used to determine the effect between
      the degree of structural organization of spleen white pulp and the percentage of
      apoptosis in the spleen. A significant effect on the level of white pulp
      morphological disorganization and percentage of apoptosis in spleen T cells was
      observed (F=20.45; P=0.0014). These data suggest that apoptosis is an important
      for the immunopathogenesis of canine visceral leishmaniasis.

PMID- 21899955
TI  - Biologic therapies in the metastatic colorectal cancer treatment continuum-
      applying current evidence to clinical practice.
AB  - More therapeutic options are now available than ever before for patients with
      metastatic colorectal cancer (mCRC) and, as such, treatment decisions have become
      more complex. A multidisciplinary approach is, therefore, required to effectively
      manage these patients. In the past few years, many trials have reported on the
      value of combining biological agents, such as those targeting vascular
      endothelial growth factor A and epidermal growth factor receptors, with
      chemotherapy. However, despite the plethora of information now available, the
      optimal treatment strategy for patients with mCRC remains unclear. Indeed, the
      propensity of investigators to conduct clinical trials utilising a variety of
      chemotherapy backbones combined with the increased complexity of retrospectively
      incorporating analyses of genetic mutation status (e.g. KRAS and BRAF) have led
      to conflicting results for seemingly similar endpoints, particularly overall
      survival. As a result, guidelines that have been developed, whilst having some
      similarities, have distinct differences in terms of suggested therapeutic
      combinations. Therefore, here, we review and distil the currently available data
      reported from phase III trials of biologic agents in the first-, second- and
      third-line mCRC settings.

PMID- 21899957
TI  - Hypoxic damage to pancreatic beta cells--the hidden link between sleep apnea and
      diabetes.
AB  - Despite a large body of epidemiologic and clinical evidence suggesting that sleep
      disordered breathing is an independent risk factor for development of type 2
      diabetes (T2DM), the underlying pathogenesis of altered glucose metabolism in
      sleep apnea remains to be unraveled. While previous studies have proposed some
      causal pathways linking sleep apnea with T2DM through increased insulin
      resistance and deterioration in insulin sensitivity, there has been a particular
      lack of research into sleep apnea-related alterations in pancreatic beta-cell
      function. Drawing upon our previous observation that sleep apnea is independently
      associated with an increased basal pancreatic beta-cell function in adults with
      normal glucose metabolism, the idea presented here suggests that sleep apnea
      imposes an excessive demand for insulin secretion, which may lead to progressive
      pancreatic beta-cell failure in high-risk individuals. Specifically, we
      hypothesize that in addition to diabetogenic effects of acute hypoxic activation
      of the sympathetic nervous system, the chronic intermittent hypoxemia represses
      the expression of key genes regulating biosynthesis of pancreatic proinsulin
      convertases with a resultant progressive decrease in their catalytic activity.
      The long-term hypoxic damage to pancreatic beta-cells may thus contribute to
      progression of glucose dysregulation in persons with untreated sleep apnea over
      time. Strategies to prevent and decrease the high prevalence and associated
      morbidity of T2DM are critically needed. The ideas and hypotheses presented here
      address the unexplored pathophysiological mechanisms underlying the potential
      causal link between sleep apnea and T2DM. Future hypotheses-testing will seek to
      delineate the role of sleep apnea in the development of T2DM, probe the
      underlying molecular mechanisms for pancreatic beta-cell dysfunction in sleep
      apnea, and obtain information on clinical, epidemiologic, and other factors
      responsible for protecting individuals from alterations in insulin-glucose
      homeostasis. These results could further be utilized in testing genetic
      susceptibilities and various therapy modalities to prevent pancreatic beta-cell
      dysfunction and maintain normal glucose status in persons with sleep apnea in the
      long term.

PMID- 21899956
TI  - Stress alters personal moral decision making.
AB  - While early studies of moral decision making highlighted the role of rational,
      conscious executive processes involving frontal lobe activation more recent work
      has suggested that emotions and gut reactions have a key part to play in moral
      reasoning. Given that stress can activate many of the same brain regions that are
      important for and connected to brain centres involved in emotional processing we
      sought to evaluate if stress could influence moral decision making. Sixty-five
      undergraduate volunteers were randomly assigned to control (n=33) and
      experimental groups (n=32). The latter underwent the Trier Social Stress Test
      (TSST) and induction of stress was assessed by measurement of salivary cortisol
      levels. Subjects were then required to provide a response to thirty moral
      dilemmas via a computer interface that recorded both their decision and reaction
      time. Three types of dilemmas were used: non-moral, impersonal moral and personal
      moral. Using a binary logistic model there were no significant predicators of
      utilitarian response in non-moral and impersonal moral dilemmas. However the
      stressed group and females were found to predict utilitarian responses to
      personal moral dilemmas. When comparing percentage utilitarian responses there
      were no significant differences noted for the non-moral and impersonal moral
      dilemmas but the stressed group showed significantly less utilitarian responses
      compared to control subjects. The stress response was significantly negatively
      correlated with utilitarian responses. Females also showed significantly less
      utilitarian responses than males. We conclude that activation of the stress
      response predisposed participants to less utilitarian responses when faced with
      high conflict personal moral dilemmas and suggest that this offers further
      support for dual process theory of moral judgment. We also conclude that females
      tend to make less utilitarian personal moral decisions compared to males,
      providing further evidence that there are gender differences in moral reasoning.

PMID- 21899958
TI  - Polymorphism and parent-of-origin effects on gene expression of CAST, leptin and
      DGAT1 in cattle.
AB  - This study aimed to investigate differential allele expression (DAE) and
      polymorphism and parent-of-origin effects on expression of genes related to beef
      traits. CAST, related to meat tenderness, and DGAT1 and leptin, related to fat
      deposition, were evaluated. In bovine fetal tissues CAST was expressed twice as
      much (P < 0.05) in muscle of homozygous GG than in heterozygous AG. Leptin was
      expressed about one-tenth as much (P < 0.05) in heterozygous TpCm (allele T of
      paternal origin and allele C of maternal origin) than in homozygous CC. No DAE
      was observed. The evidence of polymorphism effect on expression of CAST and
      parent-of-origin effect on leptin contributes to a better understanding of events
      controlling the expression of genes of economic interest in cattle. Furthermore,
      if the parent-of-origin effects observed in fetal tissues are confirmed in adult
      tissues and associated to phenotypic variation, this parental origin criterion
      may be considered in marker-assisted selection of beef traits.

PMID- 21899960
TI  - A novel spatial and stochastic model to evaluate the within and between farm
      transmission of classical swine fever virus: II validation of the model.
AB  - A new, recently published, stochastic and spatial model for the evaluation of
      classical swine fever virus (CSFV) spread into Spain has been validated by using
      several methods. Internal validity, sensitivity analysis, validation using
      historical data, comparison with other models and experiments on data validity
      were used to evaluate the overall reliability and consistency of the model. More
      than 100 modifications in input data and parameters were evaluated. Outputs were
      obtained after 1000 iterations for each new scenario of the model. As a result,
      the model was shown to be consistent, being the probability of infection by local
      spread, the time from infectious to clinical signs state, the probability of
      detection based on clinical signs at day t after detection of the index case
      outside the control and surveillance zones and the maximum number of farms to be
      depopulated at day t the parameters that have more influence (>10% of change) on
      the magnitude and duration of the epidemic. The combination of a within- and
      between-farm spread model was also shown to give significantly different results
      than using a purely between-farm spread model. Methods and results presented here
      were intended to be useful to better understand and apply the model, to identify
      key parameters for which it will be critical to have good estimates and to
      provide better support for prevention and control of future CSFV outbreaks.

PMID- 21899959
TI  - Reciprocal inhibitory effects of intravenous d-methamphetamine self
      administration and wheel activity in rats.
AB  - BACKGROUND: Some epidemiological and cessation studies suggest physical exercise
      attenuates or prevents recreational drug use in humans. Preclinical studies
      indicate that wheel activity reduces cocaine self-administration in rats; this
      may, however, require the establishment of compulsive wheel activity. METHODS:
      Effects of concurrent wheel activity on intravenous d-methamphetamine (METH) self
      administration were examined in male Wistar and Sprague Dawley rats with
      negligible prior wheel experience. Wistar rats self-administered METH (0.05
      mg/kg/inf) under a fixed-ratio 1 (FR1) schedule with concurrent access to an
      activity wheel during sessions 1-14, 8-21 or 15-21. Control rats which did not
      self-administer METH had access to an activity wheel during sessions 1-14, 8-21
      or 15-28. Sprague Dawley rats self-administered METH (0.1 mg/kg/inf) under FR1
      for 14 sessions with either concurrent access to a locked or an unlocked activity
      wheel. RESULTS: METH self-administration was lower when the wheel was available
      concurrently from the start of self-administration training in both strains, even
      though Sprague Dawley rats self-administered twice as many METH infusions and ran
      one-sixth as much on the wheel compared to Wistar rats. Wheel access initiated
      after 7 or 14 days had no effect on METH self-administration in Wistar rats.
      Wheel activity was significantly reduced in these groups compared with the group
      with concurrent wheel and METH access for the first 14 sessions. CONCLUSIONS:
      These data show that METH self-administration is reduced by exercise if initiated
      from the start of self-administration and that prior METH self-administration
      experience interferes with the value of exercise as a reinforcer.

PMID- 21899962
TI  - The first detection of methicillin-resistant Staphylococcus aureus ST398 in pigs
      in Korea.
AB  - In order to determine the presence of methicillin-resistant Staphylococcus aureus
      (MRSA) in pigs in Korea, a total of 657 nasal swabs were collected from pigs on
      66 different pig farms nationwide during February 2008-May 2009. The prevalences
      of MRSA positive samples in pigs and farms were 3.2% (21/657) and 22.7% (15/66),
      respectively. Two different types were found among the 21 MRSA isolates: 17
      strains of livestock-associated type (LA; ST398 or ST541/spa t034) and 4 strains
      of human-associated type (HA; ST72/spa t664 or t2461). The most prevalent type of
      MRSA strain was ST398/t034 (12/21, 57%), followed by ST541/t034 (5/21, 23.8%).
      The rest of the isolates were ST72/t664 (n=2) and ST72/t2461 (n=2), respectively.
      Our data provide evidence for the existence of not only LA types (ST398 and
      ST541) but also HA type (ST72) MRSA in pigs in Korea. This survey provides the
      first evidence of LA type MRSA in animals in Korea. In addition, the presence of
      human MRSA clones in pigs observed in this study suggests an additional reservoir
      for human MRSA infection, and vice versa.

PMID- 21899961
TI  - Genotypes and antibiotic resistance of Campylobacter coli in fattening pigs.
AB  - Campylobacter coli is a food-borne zoonotic pathogen causing human
      gastroenteritis worldwide. The organism is a commensal in the intestine of many
      food production animals including fattening pigs. The role of the pig as a
      potential reservoir for C. coli affecting human either directly or via poultry
      has hardly been investigated and genetic characterization of porcine strains is
      needed to address this question. For this aim multilocus sequence typing (MLST)
      and flaB typing was applied to 256 C. coli isolates from faeces of fattening pig
      collected during 2009 at different slaughterhouses in Switzerland. In addition
      genotypic resistances towards macrolides and quinolones based on point mutations
      in the 23S rRNA and gyrA genes, respectively, were determined. Of the 67 sequence
      types (STs) obtained by MLST, 37 were found for the first time. flaB typing
      revealed 46 different types with 14 of them being novel and was useful to further
      differentiate strains with an identical ST. Quinolone resistance was detected in
      33.6% and macrolide resistance was found in 10.6% of isolates. Comparison with 99
      C. coli pig isolates from 2001 revealed a significant decrease in antibiotic
      resistance towards both groups of antibiotics and there was high overlap between
      genotypes of 2001 and 2009. Little overlap of porcine genotypes was found with 97
      C. coli isolates from poultry collected 2008, however, macrolide resistance was
      significantly higher in pig isolates. In conclusion, C. coli from Swiss pig are
      heterogeneous containing many novel STs, findings that could reflect the
      partitioned Swiss pig production with almost no international breed exchange. The
      antibiotic resistance echoes the use of corresponding drugs in the Swiss
      livestock production and indicates the efficacy of restrictive application of
      antibiotics in order to reduce resistances.

PMID- 21899963
TI  - Associations among milk production and rectal temperature on pregnancy
      maintenance in lactating recipient dairy cows.
AB  - The objective of this study was to evaluate the associations among milk
      production, rectal temperature, and pregnancy maintenance in lactating recipient
      dairy cows. Data were collected during an 11-mo period from 463 Holstein cows
      (203 primiparous and 260 multiparous) assigned to a fixed-time embryo transfer
      (ET) protocol. Only cows detected with a visible corpus luteum immediately prior
      to ET were used. Rectal temperatures were collected from all cows on the same day
      of ET. Milk production at ET was calculated by averaging individual daily milk
      production during the 7d preceding ET. Pregnancy diagnosis was performed by
      transrectal ultrasonography 21d after ET. Cows were ranked and assigned to groups
      according to median milk production (median=35kg/d; HPROD=above median;
      LPROD=below median) and rectal temperature (<=39.0 degrees C=LTEMP; >39.0 degrees
      C=HTEMP). A milk production*temperature group interaction was detected (P=0.04)
      for pregnancy analysis because HTEMP cows ranked as LPROD were 3.1 time more
      likely to maintain pregnancy compared with HTEMP cows ranked as HPROD (P=0.03).
      Milk production did not affect (P=0.55) odds of pregnancy maintenance within
      LTEMP cows, however, and no differences in odds of pregnancy maintenance were
      detected between HTEMP and LTEMP within milk production groups (P>0.11). Within
      HTEMP cows, increased milk production decreased the probability of pregnancy
      maintenance linearly, whereas within LTEMP cows, increased milk production
      increased the probability of pregnancy maintenance linearly. Within HPROD,
      increased rectal temperature decreased the probability of pregnancy maintenance
      linearly, whereas within LPROD cows, no associations between rectal temperatures
      and probability of cows to maintain pregnancy were detected. In summary, high
      producing dairy cows with rectal temperatures below 39.0 degrees C did not
      experience reduced pregnancy maintenance to ET compared to cohorts with reduced
      milk production.

PMID- 21899964
TI  - Is an ovulation-inducing factor (OIF) present in the seminal plasma of rabbits?
AB  - The objectives of this study were (1) to determine the effect of rabbit seminal
      plasma on LH secretion and ovulation using the llama animal model as an in vivo
      ovulation bioassay and (2) to determine the effect of llama or rabbit seminal
      plasma on ovulation induction in the rabbit model. In Experiment 1, llamas with a
      growing follicle >=8mm in diameter were assigned randomly to one of three groups
      (n=5 per group) and given an intramuscular dose of 1mL of: (a) llama seminal
      plasma, (b) rabbit seminal plasma, or (c) phosphate buffered saline (PBS;
      negative control). Blood samples for LH measurement were taken every 15 min from
      1.5 h before to 8 h after treatment (Day 0: starting of treatment). Llamas were
      examined by ultrasonography every 12h from treatment to ovulation, and then every
      other day until Day 16 after treatment to evaluate corpus luteum (CL)
      development. Blood samples for progesterone measurement were taken every other
      day from Day 0 to Day 16. Ovulation was detected in 4 of 5, 5 of 5, and 0 of 0
      llamas treated with llama or rabbit seminal plasma and PBS, respectively
      (P<0.001). After treatment, plasma LH concentration increased and decreased
      (P<0.01) in the llama and rabbit seminal plasma group but not in the PBS-treated
      group. No differences were observed on CL development (P>=0.3) and progesterone
      secretion (P>0.05) between both seminal plasma treated groups. In Experiment 2,
      receptive female rabbits (n=5-7 per group) were given an intramuscular dose of:
      (a) 0.5, (b) 1.0 and (c) 2.0mL of either rabbit or llama seminal plasma, (d)
      0.5mL PBS (negative control), or (e) 25MUg of gonadoreline acetate (GnRH;
      positive control). Does were submitted to laparotomy 24-36 h after treatment to
      determine the ovulatory response and the presence of antral and hemorrhagic
      anovulatory follicles. Ovulation sites (7.0+/-0.6) were only detected in GnRH
      treated does (P<0.01). There was an increase (P<0.01), in the total number of
      follicles (antral plus hemorraghic follicles) in those females treated with 1mL
      of rabbit seminal plasma and there was a tendency (P=0.08) for more hemorrhagic
      anovulatory follicles in does treated with 1.0 and 2.0mL of either rabbit or
      llama seminal plasma. Results document the presence of OIF in the seminal plasma
      of rabbits. The differential ovulatory response between species, however,
      requires further investigation.

PMID- 21899965
TI  - Forensic identification of resampling operators: A semi non-intrusive approach.
AB  - Recently, several new resampling operators have been proposed and successfully
      invalidate the existing resampling detectors. However, the reliability of such
      anti-forensic techniques is unaware and needs to be investigated. In this paper,
      we focus on the forensic identification of digital image resampling operators
      including the traditional type and the anti-forensic type which hides the trace
      of traditional resampling. Various resampling algorithms involving geometric
      distortion (GD)-based, dual-path-based and postprocessing-based are investigated.
      The identification is achieved in the manner of semi non-intrusive, supposing the
      resampling software could be accessed. Given an input pattern of monotone signal,
      polarity aberration of GD-based resampled signal's first derivative is analyzed
      theoretically and measured by effective feature metric. Dual-path-based and
      postprocessing-based resampling can also be identified by feeding proper test
      patterns. Experimental results on various parameter settings demonstrate the
      effectiveness of the proposed approach.

PMID- 21899966
TI  - Evaluation of ability for basic movement scale for children type T (ABMS-CT) for
      disabled children.
AB  - BACKGROUND: The objective of this pilot study was to test the validity and
      reliability of a new scale, the Ability for Basic Movement Scale for Children
      Type T (ABMS-CT). METHODS: Forty-nine pediatric patients with disabilities (aged
      1.00-15.17years; 29 males and 20 females) participated in this prospective study.
      To prove the validity and reliability of the ABMS-CT, subjects were administered
      the ABMS-CT by two physicians. In addition to the ABMS-CT score, data on age,
      diagnosis, and results of the Functional Independence Measure for Children
      (WeeFIM) were recorded. RESULTS: Spearman's rank correlation coefficient analysis
      showed that the ability to perform basic movements according to the individual
      scores for each item on the ABMS-CT and the total scores of the ABMS-CT
      correlated significantly with the total scores of the motor and cognitive WeeFIM,
      respectively (r=0.753-0.892, p=0.0001). The five items on the ABMS-CT had
      appropriate internal consistency (Cronbach's alpha=0.966). Inter-rater
      reliability analysis indicated that the "oral and facial area", "hands and
      fingers", "one leg", "both legs", and "stairs" items on the ABMS-CT had almost
      perfect reliability (kappa=0.854-0.925). CONCLUSION: This study provides evidence
      for the validity and reliability of the ABMS-CT with regard to assessment of the
      functional ability for complex movements in disabled pediatric patients even if
      they can walk independently.

PMID- 21899967
TI  - [ICD-10 adaptation of 15 Agency for Healthcare Research and Quality patient
      safety indicators].
AB  - BACKGROUND: In the United States, the Agency for Healthcare Research and Quality
      (AHRQ) has developed 20 Patient Safety Indicators (PSIs) to measure the
      occurrence of hospital adverse events from medico-administrative data coded
      according to the ninth revision of the international classification of disease
      (ICD-9-CM). The adaptation of these PSIs to the WHO version of ICD-10 was carried
      out by an international consortium. METHODS: Two independent teams transcoded ICD
      9-CM diagnosis codes proposed by the AHRQ into ICD-10-WHO. Using a Delphi
      process, experts from six countries evaluated each code independently, stating
      whether it was "included", "excluded" or "uncertain". During a two-day meeting,
      the experts then discussed the codes that had not obtained a consensus, and the
      additional codes proposed. RESULTS: Fifteen PSIs were adapted. Among the 2569
      proposed diagnosis codes, 1775 were unanimously adopted straightaway. The 794
      remaining codes and 2541 additional codes were discussed. Three documents were
      prepared: (1) a list of ICD-10-WHO codes for the 15 adapted PSIs; (2)
      recommendations to the AHRQ for the improvement of the nosological frame and the
      coding of PSI with ICD-9-CM; (3) recommendations to the WHO to improve ICD-10.
      CONCLUSIONS: This work allows international comparisons of PSIs among the
      countries using ICD-10. Nevertheless, these PSIs must still be evaluated further
      before being broadly used.

PMID- 21899968
TI  - [Management and prevention of invasive fungal infections in haematology].

PMID- 21899969
TI  - A dedicated BI-RADS training programme: effect on the inter-observer variation
      among screening radiologists.
AB  - INTRODUCTION: The Breast Imaging Reporting and Data System (BI-RADS) was
      introduced in the Dutch breast cancer screening programme to improve
      communication between medical specialists. Following introduction, a substantial
      variation in the use of the BI-RADS lexicon for final assessment categories was
      noted among screening radiologists. We set up a dedicated training programme to
      reduce this variation. This study evaluates whether this programme was effective.
      MATERIALS AND METHODS: Two comparable test sets were read before and after
      completion of the training programme. Each set contained 30 screening mammograms
      of referred women selected from screening practice. The sets were read by 25
      experienced and 30 new screening radiologists. Cohen's kappa (kappa) was used to
      calculate the inter-observer agreement. The BI-RADS 2003 version was implemented
      in the screening programme as the BI-RADS 2008 version requires the availability
      of diagnostic work-up, and this is unavailable. RESULTS: The inter-observer
      agreement of all participating radiologists (n=55) with the expert panel
      increased from a pre-training kappa-value of 0.44 to a post-training kappa-value
      of 0.48 (p=0.14). The inter-observer agreement of the new screening radiologists
      (n=30) with the expert panel increased from kappa=0.41 to kappa=0.50 (p=0.01),
      whereas there was no difference in agreement among the 25 experienced
      radiologists (from kappa=0.48 to kappa=0.46, p=0.60). CONCLUSION: Our training
      programme in the BI-RADS lexicon resulted in a significant improvement of
      agreement among new screening radiologists. Overall, the agreement among
      radiologists was moderate (guidelines Landis and Koch). This is in line with
      results found in the literature.

PMID- 21899970
TI  - 18F-FDG PET or PET/CT for detecting extrahepatic metastases or recurrent
      hepatocellular carcinoma: a systematic review and meta-analysis.
AB  - AIM: Positron emission tomography (PET) using F18-flurodeoxy-glucose (FDG) has
      been widely used for reflecting cellular metabolism. However, the feasibility of
      FDG PET in the diagnosis of hepatocellular carcinoma (HCC) is limited. The aim of
      the study was to assess the ability of FDG PET (PET/CT) in the detection of
      extrahepatic metastases or recurrent HCC. MATERIALS AND METHODS: We conducted
      MEDLINE, EMBASE and COCHRANE searches (last update, April 2011). Eight eligible
      articles were identified evaluating F18-FDG PET (PET/CT) in extrahepatic
      metastases or recurrent HCC. Two authors independently evaluated the
      methodological quality of each study. We estimated pooled sensitivities,
      specificities, summary receiver-operating-characteristic (SROC) curves, and
      summary likelihood ratios. RESULTS: Eight eligible studies were enrolled in this
      study. The pooled estimates of sensitivity, specificity, positive likelihood
      ratio, and negative likelihood ratio of FDG PET (PET/CT) in the detection of
      metastatic HCC were 76.6%, 98.0%, 14.68, and 0.28, respectively. The pooled
      estimates of sensitivity, specificity, LR+ and LR- of FDG PET (PET/CT) in the
      detection of recurrent HCC were 81.7%, 88.9%, 4.72, and 0.19, respectively.
      CONCLUSION: Based on the results of this systematic review, F-18 FDG PET (PET/CT)
      was useful in ruling in extrahepatic metastases of HCC and valuable for ruling
      out the recurrent HCC.

PMID- 21899971
TI  - Clinical value of FDG PET or PET/CT in urinary bladder cancer: a systemic review
      and meta-analysis.
AB  - AIM: The purpose of the current study was to conduct a systemic review and meta
      analysis of the published literature to evaluate the diagnostic accuracy of FDG
      PET or PET/CT in urinary bladder cancer. MATERIALS AND METHODS: The authors
      conducted a systematic MEDLINE search of articles published between January 2000
      and December 2010. Two reviewers independently assessed the methodological
      quality of each study. We conducted a meta-analysis of pooled sensitivity and
      specificity in detecting primary and metastatic lesions of bladder cancer.
      RESULTS: Six studies met the inclusion criteria. The pooled sensitivity and
      specificity of PET/CT for primary lesion detection of bladder cancer were 0.90
      (95% CI: 0.70-0.99) and 1.00 (95% CI: 0.74-1.00), respectively. The pooled
      sensitivity and specificity of FDG PET or PET/CT for staging or restaging
      (metastatic lesions) of bladder cancer were 0.82 (95% CI: 0.72-0.89) and 0.89
      (95% CI: 0.81-0.95), respectively. CONCLUSION: The diagnostic accuracy of FDG PET
      or PET/CT is good in metastatic lesions of urinary bladder cancer. Due to the
      small number of patients and limited number of studies analyzed, the diagnostic
      capability of FDG PET or PET/CT in detection of primary bladder wall lesions
      could not be assessed.

PMID- 21899972
TI  - Peripheral neural sheath tumors (PNST)--what a radiologist should know.
AB  - Peripheral neural sheath tumors (PNST) are rare and the common goal of management
      focuses on eliminating pain and maximizing function of the affected nerve.
      Therefore preoperative assessment of the specific morphological behaviour of such
      tumors regarding the nerves internal architecture is of utmost importance. PNSTs
      may affect one or more fascicles of a peripheral nerve resulting in a significant
      functional loss after resection and the necessity of functional reconstruction in
      one step. Enhancement of preoperative information should also address the
      biological behaviour of the tumor regarding its dignity and the resulting
      implications on amount of radical resection, additional treatment and prognosis.
      Since high-resolution techniques promise more and more detail resolution in many
      fields of imaging, delineation of intra- and extraneural processes as well as
      biological informations shall lead towards a well prepared and foreseeable image
      guided treatment of PNSTs.

PMID- 21899973
TI  - Gaiella occulta gen. nov., sp. nov., a novel representative of a deep branching
      phylogenetic lineage within the class Actinobacteria and proposal of Gaiellaceae
      fam. nov. and Gaiellales ord. nov.
AB  - Two isolates, with an optimum growth temperature of about 35-37 degrees C and an
      optimum pH for growth between 6.5 and 7.5, were recovered from a deep mineral
      water aquifer in Portugal. Strains form rod-shaped cells and were non-motile.
      These strains were non-pigmented, strictly aerobic, catalase and oxidase
      positive. Strains F2-233(T) and F2-223 assimilated carbohydrates, organic acids
      and amino acids. Major fatty acids were novel iso internally branched such as
      17:0 iso 10-methyl, 17:0 iso and 15:0 iso 8-methyl. The peptidoglycan contained
      meso-diaminopimelic acid and menaquinone MK-7 was the major respiratory quinone.
      Analysis of the 16S rRNA gene shows the strains to cluster with species of the
      genera Thermoleophilum, Patulibacter, Conexibacter and Solirubrobacter to which
      they have pairwise sequence similarity in the range 87-88%. Based on 16S rRNA
      gene sequence analysis, physiological and biochemical characteristics we describe
      a new species of a novel genus represented by strain F2-233(T) (=CECT 7815(T)=LMG
      26412(T)) for which we propose the name Gaiella occulta gen. nov., sp. nov. We
      also propose that this organism represents a novel family named Gaiellaceae fam.
      nov. of a novel order named Gaiellales ord. nov.

PMID- 21899974
TI  - X-ray powder diffractometry and liquid chromatography studies of sibutramine and
      its analogues content in herbal dietary supplements.
AB  - The contemporary societies of the developed countries are prone to use
      traditional far-east medicines as remedies for all diseases. Some of them, such
      as obesity, might be classified as civilization diseases. Combating the problem,
      people try not only several miraculous diets but also herbal infusions (teas) and
      variety of "herbal" preparations. All these believing that such treatment is
      healthy and harmless as far as it is "natural". Leaving out of the way the
      question if herbal medicines can be taken safely without doctors' control the
      query arises if the common preparations are strictly natural and herbal. Here we
      report examples of quality studies of such medicines using both X-ray powder
      diffraction (XRPD) and liquid chromatography (LC) with various types of
      detection: ultraviolet (UV), coulometric electrode array (CEAD) and time-of
      flight mass spectrometry (TOF-MS). Especially the XRPD assisted with an optical
      microscopy seems to be useful as a fast screening method of general sample
      composition of such preparations. First of all it can discriminate between
      capsules containing pure herbal materials and those with some chemical.

PMID- 21899975
TI  - Detection of toxigenic Clostridium difficile in pediatric stool samples: an
      evaluation of Quik Check Complete Antigen assay, BD GeneOhm Cdiff PCR, and
      ProGastro Cd PCR assays.
AB  - The performance of C. Diff Quik Chek Complete (QCC), BD GeneOhm Cdiff PCR (BD),
      and ProGastro Cd PCR (PG) assays was evaluated in detecting Clostridium difficile
      infection (CDI) in children using 200 frozen stool specimens. The results of the
      tests were compared to the toxigenic culture (TC) as 'gold standard.' The
      sensitivity, specificity, positive predictive value, and negative predictive
      value were as follows. QCC antigen (GDH + Toxin-A/B) = 70.8%, 97.4%, 89.5%, and
      91.4%; BD PCR = 89.6%, 96.7%, 89.6%, and 96.7%; PG PCR = 100%, 93.4%, 82.8%, and
      100%. Polymerase chain reaction (PCR) assays detected an additional 11 positives
      missed by TC, 7 of which were confirmed positive by an alternate tcdB gene PCR
      assay. However, retrospective clinical chart review indicated CDI in only 3 of
      the 11 patients in whom C. difficile was detected by PCR only. A 2-step algorithm
      utilizing QCC antigen test as a screening test followed by confirmation of GDH
      positive and toxin-negative samples with either BD or PG PCR assay will provide
      rapid and accurate results for majority of the samples and reduce laboratory
      testing cost.

PMID- 21899976
TI  - Simple and rapid detection of human enterovirus 71 by reverse-transcription and
      loop-mediated isothermal amplification: cryopreservation affected the detection
      ability.
AB  - Human enterovirus 71 (EV71) is the primary pathogen of hand, foot, and mouth
      disease (HFMD). EV71 infection may lead to neurologic damage, with higher
      incidence of fatality compared with other HFMD pathogens. An effective drug or
      vaccine against EV71 infection is currently unavailable. It is desirable to
      determine the pathogen of HFMD accurately and quickly for early treatment. In the
      current study, reverse-transcription and loop-mediated isothermal amplification
      (RT-LAMP) technology were developed to detect EV71. The efficacy of detecting
      EV71 was compared with regular nested reverse-transcription polymerase chain
      reaction (RT-PCR). After detecting 108 clinical specimens, results showed that RT
      LAMP can specifically detect EV71, but not Coxsackie virus A16, and exhibited a
      specificity of 100% and a sensitivity of 97.1%, which was higher than regular RT
      PCR. The findings indicate that RT-LAMP is a practical method for EV71 diagnostic
      applications, particularly in small county institutes of medical service. The
      detection ability of RT-LAMP was significantly affected by cryopreservation as
      the clinical specimens were repeatedly subject to freezing and thawing
      treatments.

PMID- 21899977
TI  - Clinical laboratory evaluation of Invader(r) chemistry and hybrid capture for
      detection of high-risk human papillomavirus in liquid-based cytology specimens.
AB  - A laboratory-developed test for high-risk human papillomavirus (HPV) that
      utilizes the Invader technology (Hologic, Madison, WI, USA) was compared to
      hybrid capture (Digene, Gaithersburg, MD, USA). A total of 342 ThinPrep specimens
      were de-identified following cytology screening (10 high-grade squamous
      intraepithelial lesions, 14 low-grade squamous intraepithelial lesions, 199
      atypical squamous cells of undetermined significance, 119 normal). DNA was
      manually extracted prior to interrogation with Invader. Hybrid capture/Invader
      discrepancies were subject to HPV sequencing. One sample (0.3%) was indeterminate
      by Invader due to low genomic DNA content. Concordance of 341 available tandem
      hybrid capture/Invader results occurred at a rate of 91.5%. Differences in HPV
      detection rate between the 2 assays were not statistically significant (P =
      0.17). A propensity for false-positive hybrid capture result was confirmed by HPV
      sequencing in 83% of instances. Manual DNA extraction efficacy did not
      statistically differ between cytologic classifications (P >= 0.19). Invader
      detection of high-risk HPV is comparably sensitive and more specific than hybrid
      capture, providing an alternative for molecular HPV detection.

PMID- 21899978
TI  - Identification and characterization of plasmid-borne erm(T) macrolide resistance
      in group B and group A Streptococcus.
AB  - One hundred and seven group B Streptococcus (GBS) isolates and 344 group A
      Streptococcus (GAS) isolates were collected between 2005 and 2009 from 2 area
      hospitals and studied for resistance to erythromycin (ERY) and clindamycin (CLI)
      and the presence of the erm(T) macrolide resistance gene. The erm(T) gene was
      found in 5 (8%) of 61 erythromycin nonsusceptible GBS isolates and in 22 (55%) of
      40 erythromycin nonsusceptible GAS isolates. The erm(T) gene in all 27 GBS/GAS
      erm(T) gene-positive isolates was located on a plasmid. Three erm(T) gene
      positive plasmids were DNA sequenced. Two plasmids (1 each from GBS and GAS
      isolates) were both 4967 bp in size, contained the erm(T) gene, and differed by
      only 2 base pairs, suggesting interspecies horizontal transfer of the erm(T) gene
      containing plasmid. The third (GBS) plasmid was 6825 bp in size and contained
      GBSi1, a group II bacterial intron, as well as the erm(T) gene. Pulsed-field gel
      electrophoresis of all 27 erm(T) gene containing isolates and a selection of
      erm(T) gene-negative isolates indicated possible clonal expansion among erm(T)
      gene containing GAS isolates, but not among the 5 erm(T) gene-positive GBS
      isolates.

PMID- 21899979
TI  - Emergence of carbapenemases in Gram-negative bacteria in Hamburg, Germany.
AB  - We analyzed a collection of carbapenem-resistant Gram-negative bacterial isolates
      and detected VIM-1, VIM-2, and KPC-2 in diverse enterobacterial species and
      Pseudomonas aeruginosa isolates. Our findings suggest a more widespread
      dissemination of carbapenemases in Germany than currently appreciated.

PMID- 21899980
TI  - Prevalence of beta-lactam nonsusceptible Gram-negative bacilli and use and
      interpretation of current susceptibility breakpoints: a survey of infectious
      disease physicians.
AB  - Beta-lactam-resistant Enterobacteriaceae represent an important public health
      problem; however, questions exist about their prevalence and the impact of recent
      breakpoint changes on clinical practice. We surveyed infectious disease
      physicians to better understand these issues. Many reported encountering
      resistant Enterobacteriaceae; respondents generally favored a more conservative
      interpretation of antimicrobial susceptibility results.

PMID- 21899981
TI  - Further evaluation of the characteristics of Treponema pallidum-specific IgM
      antibody in syphilis serofast reaction patients.
AB  - Syphilis serofast reaction (SSR) is common in clinical work. From June 2005 to
      May 2009, 1208 syphilis patients were chosen for research by the Xiamen Center of
      Clinical Laboratory in China. Serologic tests were performed with toluidine red
      unheated serum test (TRUST) and Treponema pallidum particle agglutination (TPPA).
      Then, T. pallidum-specific IgM antibody (TP-IgM) was detected with fluorescent
      treponemal antibody absorption (FTA-Abs) and TPPA. In this study, patients were
      divided into the following experimental groups according to the results of TRUST
      and TPPA: (1) the SSR group consisted of 411 cases with (+) TRUST and (+) TPPA,
      and without clinical manifestations after 1 year of recommended syphilis
      treatment; (2) the serum cure group, which was further subdivided into group A
      consisting of 251cases with (-) TRUST and (+) TPPA; (3) group B consisting of 546
      cases with (-) TRUST and (-) TPPA; and (4) the blood donor control group which
      consisted of 100 cases. We demonstrated that a total of 136 cases (33.09%) of 411
      SSR patients were TP-IgM positive by TPPA, and this percentage was markedly
      higher than that in serum cure group A (9.16%). FTA-Abs analyses revealed similar
      results. All samples in serum cure group B and the control group were TP-IgM
      negative, which is identical to our previous report. The present study also
      indicated that the TP-IgM positive rate was not significantly different among
      patients with different ages, genders, and clinical phases after 1 year of
      recommended therapy. From the total of 1208 syphilis patients, 289 were randomly
      selected for TP-DNA detection by fluorescence quantitative polymerase chain
      reaction, and the positive rate of TP-DNA was 32.53%, which was slightly higher
      than that of FTA-Abs TP-IgM, and no statistically significant difference by chi
      square tests, indicating the TP-DNA result is preferably consistent with FTA-Abs
      and supporting our deduction that TP-IgM could be used as a serologic marker for
      the relapse and infection of syphilis.

PMID- 21899982
TI  - Quality of life after immediate breast reconstruction and skin-sparing mastectomy
      - a comparison with patients undergoing breast conserving surgery.
AB  - BACKGROUND: Historically breast cancer surgery was associated with significant
      psychosocial morbidity and suboptimal cosmetic outcome. Recent emphasis on
      women's quality of life following breast cancer treatment has drawn attention to
      the importance of aesthetic outcome and potential benefits of immediate breast
      reconstruction (IBR). Our primary aim was to assess patient's quality of life
      after IBR, compared to a matched group undergoing breast conservation. We also
      investigated the oncological safety and morbidity associated with immediate
      reconstruction. METHODS: A prospectively collected database of all breast cancer
      patients who underwent IBR at a tertiary referral breast unit was reviewed.
      Patients were reviewed clinically, and administered two validated quality of life
      questionnaires, at least one year after completing their treatment. RESULTS: 255
      patients underwent IBR following mastectomy over a 55 month period.
      Reconstruction with ipsilateral latissimus dorsi flap was most commonly performed
      (88%). After mean follow-up of 36 months, IBR patients' quality of life was
      comparable to a group of age-matched women (n = 160) who underwent breast
      conserving surgery (p = 0.89). No patient experienced local recurrence (0%),
      distant metastases developed in 4.8% and disease related mortality was 2.2%. Post
      operative morbidities included wound infection (11.8%), chronic pain (2.0%),
      capsular contracture (11%; 36% of whom had radiotherapy) and fat necrosis
      (14.1%). No patient experienced flap loss. CONCLUSIONS: IBR is a highly
      acceptable form of treatment for women requiring mastectomy. With high rates of
      patient satisfaction, low associated morbidity, and proven oncological safety, it
      is an appropriate recommendation for all women requiring mastectomy.

PMID- 21899983
TI  - An Internet administered treatment program for obsessive-compulsive disorder: a
      feasibility study.
AB  - The present study evaluates efficacy of a new Internet-administered cognitive
      behavioral therapy (CBT) protocol, The OCD Program, designed to treat obsessive
      compulsive disorder (OCD) remotely. This protocol comprises 8 online lessons
      delivered over 8 weeks and incorporates cognitive and behavioral techniques.
      Twenty-two individuals with a principal diagnosis of OCD received CBT-based
      online lessons, homework assignments, twice weekly contact from a clinical
      psychologist, and automated emails. Eighty-one percent of participants completed
      the lessons within the 8-week program. Post-treatment and 3-month follow-up data
      were collected from 21/21 (100%) and 19/21 (91%) participants, respectively.
      Participants improved significantly on the primary outcome measures, the Yale
      Brown Obsessive Compulsive Scale and Obsessive Compulsive Inventory-Revised, with
      within-groups effect sizes (Cohen's d) at follow-up of 1.28 and 0.60,
      respectively. Participants rated the procedure as highly acceptable despite
      receiving an average of only 86min (SD=54.4min) telephone contact with the
      therapist over the 8 weeks. These results provide preliminary support for
      efficacy of Internet-administered treatment for obsessive-compulsive disorder.

PMID- 21899985
TI  - Stochastic state estimation for neural networks with distributed delays and
      Markovian jump.
AB  - This paper investigates the problem of state estimation for Markovian jump
      Hopfield neural networks (MJHNNs) with discrete and distributed delays. The MJHNN
      model, whose neuron activation function and nonlinear perturbation of the
      measurement equation satisfy sector-bounded conditions, is first considered and
      it is more general than those models studied in the literature. An estimator that
      guarantees the mean-square exponential stability of the corresponding error state
      system is designed. Moreover, a mean-square exponential stability condition for
      MJHNNs with delays is presented. The results are dependent upon both discrete and
      distributed delays. More importantly, all of the model transformations, cross
      terms bounding techniques and free additional matrix variables are avoided in the
      derivation, so the results obtained have less conservatism and simpler
      formulations than the existing ones. Numerical examples are given which
      demonstrate the validity of the theoretical results.

PMID- 21899984
TI  - Understanding the relationship between co-occurring PTSD and MDD: symptom
      severity and affect.
AB  - How to best understand theoretically the nature of the relationship between co
      occurring PTSD and MDD (PTSD+MDD) is unclear. In a sample of 173 individuals with
      chronic PTSD, we examined whether the data were more consistent with current co
      occurring MDD as a separate construct or as a marker of posttraumatic stress
      severity, and whether the relationship between PTSD and MDD is a function of
      shared symptom clusters and affect components. Results showed that the more
      severe depressive symptoms found in PTSD+MDD as compared to PTSD remained after
      controlling for PTSD symptom severity. Additionally, depressive symptom severity
      significantly predicted co-occurring MDD even when controlling for PTSD severity.
      In comparison to PTSD, PTSD+MDD had elevated dysphoria and re-experiencing - but
      not avoidance and hyperarousal - PTSD symptom cluster scores, higher levels of
      negative affect, and lower levels of positive affect. These findings provide
      support for PTSD and MDD as two distinct constructs with overlapping distress
      components.

PMID- 21899986
TI  - Three-dimensional elliptical reconstruction for stereoscopic magnetic resonance
      angiography.
AB  - Stereoscopic MRA acquires a pair of blood vessel projections at two different
      viewing angles. Previously, we have developed two algorithms to reconstruct 3-D
      blood vessels from stereoscopic MRA. The assumption we made was that blood
      vessels were tilting circular tubes and the shape of the vessel on every cross
      section was an ellipse. Since an ellipse can be represented in either algebraic
      form or parametric form, our previous algorithms reconstructed the ellipses by
      representing them in these two forms. In this paper, we further improved the
      accuracy of our previous algorithms by an order through two enhancements. The
      first improvement we made was a better method to estimate the rotation angle of
      the major axis of an ellipse. Instead of using the center of two adjacent
      ellipses to estimate the rotation angle as in our previous method, the new method
      used the projection lengths of the two views to estimate the angle. The second
      improvement we made was the equation to describe the relationship between the
      major/minor axes and the projection lengths. In our experiments, the average
      estimation error for the parametric algorithm was improved from 0.471 pixels to
      0.066 pixels. The average error for the algebraic algorithm was improved from
      0.101 pixels to 0.014 pixels.

PMID- 21899987
TI  - Early seizure termination in ictal asystole.
AB  - To evaluate the association between cerebral hypoperfusion and seizure
      termination, we compared seizure duration in seven patients with syncopal ictal
      asystole (IA), seven with non-syncopal ictal bradycardia, and ten with non
      bradycardic seizures. Mean seizure duration was 34.4+/-13 s in IA, 67+/-28.9 s in
      ictal bradycardia, and 82.1+/-31.1 in non-bradycardic seizures. These were
      significantly different (ANOVA, p<0.02). This suggests cerebral hypoxia-ischemia
      favors seizure termination.

PMID- 21899988
TI  - Morphometric analysis of subcortical structures in progressive supranuclear
      palsy: In vivo evidence of neostriatal and mesencephalic atrophy.
AB  - Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized
      by gait and postural disturbance, gaze palsy, apathy, decreased verbal fluency
      and dysexecutive symptoms, with some of these clinical features potentially
      having origins in degeneration of frontostriatal circuits and the mesencephalon.
      This hypothesis was investigated by manual segmentation of the caudate and
      putamen on MRI scans, using previously published protocols, in 15 subjects with
      PSP and 15 healthy age-matched controls. Midbrain atrophy was assessed by
      measurement of mid-sagittal area of the midbrain and pons. Shape analysis of the
      caudate and putamen was performed using spherical harmonics (SPHARM-PDM,
      University of North Carolina). The sagittal pons area/midbrain area ratio (P/M
      ratio) was significantly higher in the PSP group, consistent with previous
      findings. Significantly smaller striatal volumes were found in the PSP group -
      putamina were 10% smaller and caudate volumes were 17% smaller than in controls
      after controlling for age and intracranial volume. Shape analysis revealed
      significant shape deflation in PSP in the striatum, compared to controls; with
      regionally significant change relevant to frontostriatal and corticostriatal
      circuits in the caudate. Thus, in a clinically diagnosed and biomarker-confirmed
      cohort with early PSP, we demonstrate that neostriatal volume and shape are
      significantly reduced in vivo. The findings suggest a neostriatal and
      mesencephalic structural basis for the clinical features of PSP leading to
      frontostriatal and mesocortical-striatal circuit disruption.

PMID- 21899989
TI  - [Exogenous tooth discoloration in children: black stains].
AB  - Black-stains are a coloring frequently met in pediatric dentistry. They can be
      medically diagnosed as 1-mm borders or unfinished lines formed by a dark
      exogenous substance which follows the gingival festoon of bet coronary (in
      cervical third of the crown) temporary teeth and permanent, or they can appear in
      like points or dark spots. They are caused by bacteria anaerobic chromogenous.
      The dominant responsible species are actinomyces. Blacks-stains are ferrous
      depots, formed following a chemical interaction on the surface of the tooth
      between sulphide of hydrogen (under the effect of the anaerobic bacteria which
      are producing hydrogen) and the iron contained in the saliva (by a healthy diet)
      or that released by red blood corpuscles (in case of bloody gums). Black-stains
      are a shape of characteristic dental plaque by its flora with trend to calcify.
      It contains an insoluble iron salt with a content raised in calcium and in
      inorganic phosphor. The coloring Black-stain is a mild pathology and has no
      incidence on the vitality of the tooth. Certainly these spots are unsightly. The
      dental surgeon in current practice can deprive them. The pediatrician plays a
      leading role in the diagnosis and advice to parents and patients affected by
      these stains.

PMID- 21899990
TI  - Patterns for collaborative work in health care teams.
AB  - OBJECTIVE: The problem of designing and managing teams of workers that can
      collaborate working together towards common goals is a challenging one.
      Incomplete or ambiguous specification of responsibilities and accountabilities,
      lack of continuity in teams working in shifts, inefficient organization of teams
      due to lack of information about workers' competences and lack of clarity to
      determine if the work is delegated or assigned are examples of important problems
      related to collaborative work in healthcare teams. Here we address these problems
      by specifying goal-based patterns for abstracting the delegation and assignment
      of services. The proposed patterns should provide generic and reusable solutions
      and be flexible enough to be customizable at run time to the particular context
      of execution. Most importantly the patterns should support a mechanism for
      detecting abnormal events (exceptions) and for transferring responsibility and
      accountability for recovering from exceptions to the appropriate actor. METHOD:
      To provide a generic solution to the problematic issues arising from
      collaborative work in teams of health workers we start from definitions of
      standard terms relevant for team work: competence, responsibility, and
      accountability. We make explicit the properties satisfied by service assignment
      and delegation in terms of competences, responsibilities, and accountability in
      normal scenarios and abnormal situations that require the enactment of recovery
      strategies. Based on these definitions we specify (1) a basic terminology, (2)
      design patterns for service assignment and delegation (with and without
      supervision), and (3) an exception manager for detecting and recovering from
      exceptions. We use a formal framework to specify design patterns and exceptions.
      RESULTS: We have proved using Owicki-Gries Theory that the proposed patterns
      satisfy the properties that characterize service assignment and delegation in
      terms of competence, responsibility and accountability in normal and abnormal
      (exceptional) scenarios. We show that although abstract, the proposed patterns
      can be instantiated in an executable COGENT prototype, and can be mapped into the
      Tallis tool that enacts PROforma language specifications of medical guidelines.
      CONCLUSIONS: The proposed patterns are generic and abstract enough to capture the
      normal and abnormal scenarios of assignment and delegation of tasks in
      collaborative work in health care teams.

PMID- 21899991
TI  - The role of serum non-cholesterol sterols as surrogate markers of absolute
      cholesterol synthesis and absorption.
AB  - AIMS: To study the whole-body cholesterol metabolism in man, cholesterol
      synthesis and absorption need to be measured. Because of the complicated methods
      of the measurements, new approaches were developed including the analysis of
      serum non-cholesterol sterols. In current lipidologic papers and even in
      intervention studies, serum non-cholesterol sterols are frequently used as
      surrogate markers of cholesterol metabolism without any validation to the
      absolute metabolic variables. The present review compares serum non-cholesterol
      sterols with absolute measurements of cholesterol synthesis and absorption in
      published papers to find out whether the serum markers are valid indicators of
      cholesterol metabolism in various conditions. DATA SYNTHESIS: During statin
      treatment, during interventions of dietary fat, and in type 2 diabetes the
      relative and absolute variables of cholesterol synthesis and absorption were
      frequently but not constantly correlated with each other. In some occasions,
      especially in subjects with apolipoprotein E3/4 and E4/4 phenotypes, the relative
      metabolic markers were even more sensitive than the absolute ones to reflect
      changes in cholesterol metabolism during dietary interventions. Even in general
      population at very high absorption the homeostasis of cholesterol metabolism is
      disturbed damaging the validity of the serum markers. CONCLUSIONS: It is worth
      using several instead of only one precursor and absorption sterol marker for
      making conclusions of altered synthesis or absorption of cholesterol, and even
      then the presence of at least some absolute measurement is valuable. During
      consumption of plant sterol-enriched diets and in situations of interfered
      cholesterol homeostasis the relative markers do not adequately reflect
      cholesterol metabolism. Accordingly, the validity of the relative markers of
      cholesterol metabolism should not be considered as self-evident.

PMID- 21899992
TI  - Hawthorn special extract WS(r) 1442 increases red blood cell NO-formation without
      altering red blood cell deformability.
AB  - WS((r)) 1442 is a special extract of hawthorn leaves with flowers used for the
      treatment of mild cardiac failure. The activation of endothelial nitric oxide
      synthase (eNOS) has been shown to contribute to its vasodilating properties.
      Quite recently it has been demonstrated that red blood cells (RBCs) express a
      functional NO-synthase (rbcNOS) and rbcNOS activation has been associated with
      increased RBC deformability. The aim of the present study was to determine
      whether WS((r)) 1442 is able to activate rbcNOS, to induce NO-formation in RBC
      and to alter RBC-deformability. Blood from healthy volunteers was incubated with
      WS((r)) 1442 (25-100 MUg/ml) for up to 30 min. RbcNOS activation was detected by
      immunohistochemical staining of phosphorylated rbcNOS and NO-formation was
      examined by diaminofluorescein (DAF) fluorescence. RBC deformability was measured
      by a laser assisted optical rotational cell analyzer. Serine 1177 of RbcNOS
      (rbcNOS Ser(1177)) was time- and concentration-dependently phosphorylated by
      WS((r)) 1442. Rates of rbcNOS Ser(1177) phosphorylation were up to 149% higher in
      RBCs treated with WS((r)) 1442 in comparison to control (DMSO 0.05%). WS((r))
      1442 induced a time-dependent increase in NO-formation in RBCs which reached its
      maximum after 5 min. An increase in shear stress (0.3-50 Pa) caused an increase
      in RBC deformability. WS((r)) 1442 did not change either basal or maximal RBC
      deformability or shear stress sensitivity of RBC at normoxia. CONCLUSION: WS((r))
      1442 activates rbcNOS and causes NO-formation in RBCs. WS((r)) 1442-dependent NO
      formation however does not affect RBC-deformability at normoxia.

PMID- 21899993
TI  - Pharmacokinetic, tissue distribution and excretion of ginsenoside-Rd in rodents.
AB  - Ginsenoside-Rd (GS-Rd) is one of the major active components of Panax ginseng,
      and was shown to have the protective effects against several insults. However, we
      still lack some basic knowledge of GS-Rd, including its pharmacokinetic, tissue
      distribution and excretion in vivo in experimental animal, such as mice and rats.
      In this study, HPLC and radioactive tracer assays were performed to determine
      pharmacokinetic, tissue distribution and excretion of GS-Rd in rodents. After
      intravascular administration with 20, 50 or 150 mg/kg GS-Rd, the dynamic changes
      of GS-Rd concentrations in plasma were consistent with a two-compartment model
      while the concentration of 3H-labeled GS-Rd was rapidly reached the peak in
      plasma, and distributed to various tissues, among which the highest concentration
      was observed in the lung.

PMID- 21899995
TI  - Tanshinone I increases CYP1A2 protein expression and enzyme activity in primary
      rat hepatocytes.
AB  - This study investigated the effects of Danshen and its active ingredients on the
      protein expression and enzymatic activity of CYP1A2 in primary rat hepatocytes.
      The ethanolic extract of Danshen roots (containing mainly tanshinones) inhibited
      CYP1A2-catalyzed phenacetin O-deethylation (IC(50)=24.6 MUg/ml) in primary rat
      hepatocytes while the water extract containing mainly salvianolic acid B and
      danshenshu had no effect. Individual tanshinones such as cryptotanshinone,
      dihydrotanshinone, tanshinone IIA inhibited the CYP1A2-mediated metabolism with
      IC(50) values at 12.9, 17.4 and 31.9 MUM, respectively. After 4-day treatment of
      the rat hepatocytes, the ethanolic extract of Danshen and tanshinone I increased
      rat CYP1A2 activity by 6.8- and 5.2-fold, respectively, with a concomitant up
      regulation of CYP1A2 protein level by 13.5- and 6.5-fold, respectively. CYP1A2
      induction correlated with the up-regulation of mRNA level of aryl hydrocarbon
      receptor (AhR), which suggested a positive feedback mechanism of tanshinone I
      mediated CYP1A2 induction. A formulated Danshen pill (containing mainly danshensu
      and salvianolic acid B and the tanshinones) up-regulated CYP1A2 protein
      expression and enzyme activity, but danshensu and salvianolic acid B, when used
      individually, did not affect CYP1A2 activity. This study was the first report on
      the Janus action of the tanshinones on rat CYP1A2 activity.

PMID- 21899994
TI  - Danshen-Gegen decoction protects against hypoxia/reoxygenation-induced apoptosis
      by inhibiting mitochondrial permeability transition via the redox-sensitive
      ERK/Nrf2 and PKCepsilon/mKATP pathways in H9c2 cardiomyocytes.
AB  - Danshen-Gegen (DG) Decoction, an herbal formulation containing Radix Salviae
      miltiorrhizae and Radix Puerariae lobatae, has been used for the treatment of
      coronary artery disease in Chinese medicine. In the present study, the
      involvement of ERK- and PKCepsilon-mediated pathways in the cytoprotection
      against apoptosis afforded by DG pretreatment was investigated in H9c2
      cardiomyocytes. Pretreatment with a methanol extract of aqueous DG decoction
      protected against hypoxia/reoxygenation-induced apoptosis in H9c2 cardiomyocytes.
      The cytoprotection was associated the enhancement of cellular reduced glutathione
      and a reduced sensitivity to Ca(2+)-induced mitochondrial permeability
      transition. DG extract increased the production of cytochrome P-450 (CYP)
      dependent reactive oxygen species (ROS) in H9c2 cardiomyocytes, which was
      accompanied by the concomitant activation of ERK1/2 and PKCepsilon. The DG
      induced ERK1/2 activation was followed by the translocation of Nrf2 from the
      cytosol to the mitochondria accompanied by an increase in the expression of
      glutathione-related antioxidant proteins. In addition, the increased expression
      of hemeoxygenase-1 was associated with the activation of Akt and BAD, indicative
      of anti-apoptotic activity. In conclusion, DG treatment activated both ERK/Nrf2
      and PKCepsilon pathways, presumably by ROS arising from CYP-catalyzed processes,
      with resultant inhibition of hypoxia/reoxygenation-induced apoptosis immediately
      after DG treatment or even after an extended time interval following DG
      treatment.

PMID- 21899996
TI  - In vitro anti-influenza virus activity of a cardiotonic glycoside from Adenium
      obesum (Forssk.).
AB  - Methanolic extracts of six Saudi plants were screened for their in vitro
      antiviral activity using influenza virus A/PR/8/34 (H1N1) and MDCK cells in an
      MTT assay. The results indicated that the extracts of Adeniumobesum and
      Tephorosianubica possessed antiviral activity (99.3 and 93.3% inhibition at the
      concentration of 10 MUg/ml, respectively). Based on these results A. obesum was
      selected for further study by applying bioactivity-guided fractionation to
      isolate its antiviral principle. The antiviral principle was isolated from the
      chloroform fraction through solvent fractionation, combined open liquid
      chromatography and HPLC. The isolated active compound A was identified as
      oleandrigenin-beta-D-glucosyl (1->4)-beta-D-digitalose, on the basis of its
      spectral analysis (MS, 1D and 2D NMR). The isolated glycoside showed reduction of
      virus titre by 69.3% inhibition at concentration of 1 MUg/ml (IC(50)=0.86
      MUg/ml).

PMID- 21899998
TI  - Inflammatory activity assessment by F18 FDG-PET/CT in persistent symptomatic
      sarcoidosis.
AB  - BACKGROUND: Establishing inflammatory activity in sarcoidosis patients with
      persistent disabling symptoms is important. Whole body F(18)-FDG PET/CT (PET)
      appeared to be a sensitive method to detect inflammatory activity in newly
      diagnosed symptomatic sarcoidosis. The aim was to assess the presence of
      inflammatory activity using PET in sarcoidosis patients with unexplained
      persistent disabling symptoms and the association between PET findings and
      serological inflammatory markers. METHODS: Sarcoidosis patients who underwent a
      PET between June 2005 and June 2010 (n = 89), were retrospectively included. All
      PET scans were examined and positive findings were classified as thoracic and/or
      extrathoracic. As serological markers of inflammatory activity angiotensin
      converting enzyme (ACE), soluble interleukin-2 receptor (sIL-2R), and neopterin
      were considered. RESULTS: In 65/89 (73%) of the studied patients PET was
      positive, 52 of them (80%) had serological signs of inflammatory activity. In
      14/15 patients with a Chest X-ray stage IV PET was positive. In 80% of the PET
      positive patients extrathoracic inflammatory activity was found. Sensitivity of
      combined serological inflammatory markers for the presence of inflammatory
      activity as detected by PET was 80%, specificity 100%, positive predictive value
      100%, negative predictive value 65%. CONCLUSIONS: The majority of sarcoidosis
      patients with persistent disabling symptoms, even those with radiological stage
      IV, had PET positive findings with remarkably 80% extrathoracic lesions. In 20%
      PET was positive without signs of serological inflammatory activity. PET appeared
      to be of additional value to assess inflammatory activity in patients with
      persistent symptoms in the absence of signs of serological inflammatory activity
      and to detect extrathoracic lesions.

PMID- 21899997
TI  - The many faces of Th17 cells.
AB  - Th17 cells have been shown to be strong inducers of tissue inflammation and
      autoimmune diseases. However, not all Th17 cells are pathogenic and increasing
      data suggest that Th17 cells may come in different flavors. Thus, Th17 cells
      cannot be described using a narrow schematic, but instead Th17 cells comprise a
      wide spectrum with a range of effector phenotypes. Here, we review the key
      factors that generate such diversity, as well as the cytokines and transcription
      factors that are differentially expressed in pathogenic and nonpathogenic Th17
      cells. This new knowledge can be used to identify molecules that make Th17 cells
      pathogenic and determine how these cells could be targeted to suppress autoimmune
      diseases.

PMID- 21899999
TI  - Are pharmacists reducing COPD'S impact through smoking cessation and assessing
      inhaled steroid use?
AB  - BACKGROUND: The National Institute for Health and Clinical Excellence (NICE) COPD
      2004 guidelines recommend: * COPD patients who smoke should be encouraged to stop
      at every opportunity; * Inhaled corticosteroid should be used only among patients
      with moderate to severe COPD; * Pharmacists should identify smokers and provide
      smoking cessation advice. The community pharmacy contract requires pharmacists to
      review patients' medications, creating an opportunity for reviewing the
      prescribing of inhaled corticosteroids in COPD. The survey explored the degree to
      which community pharmacists in North West England identify and provide advice to
      smokers and assess prescribed inhaled corticosteroids among COPD patients.
      METHODS: A self-completion questionnaire was sent to 2080 community pharmacists
      from the 2005 pharmacist census database. RESULTS: Of the 1051 (50.5%)
      respondants, 37.1% mentioned COPD as a risk from smoking most or every time and
      54.5% sometimes or rarely, and 19.6% routinely asked about smoking status when
      dispensing COPD medication. Pharmacists with more than 20 years experience were
      more likely to have read the Guideline compared to pharmacists with 10 years or
      less (OR: 1.54; 95% CI: 1.13 to 2.10). Pharmacists who had read the NICE
      Guideline (46.8%) were around twice as likely to mention COPD as a risk of
      smoking, ask about COPD if inhaled corticosteroids were dispensed and ask about
      smoking routinely if COPD medication was dispensed. (p<0.005). CONCLUSION: The
      NICE guidelines on COPD encourage community pharmacists to carry out smoking
      cessation and educational interventions, but further support is needed.

PMID- 21900000
TI  - Pulmonary alveolar proteinosis: new insights from a single-center cohort of 70
      patients.
AB  - BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized
      by the intra-alveolar accumulation of surfactant lipids and proteins. The aim of
      the study is to describe the epidemiologic, clinical, physiologic, and laboratory
      features of PAP in a large single-center cohort of patients with PAP. STUDY
      POPULATION: Over 30 years, 70 patients with PAP were managed at our institution,
      64 with primary and 6 with secondary PAP. RESULTS: The mean age at diagnosis was
      43 years with a male to female ratio of 1.3. BAL was the most commonly applied
      diagnostic method, performed in 83% of cases. A history of smoking was seen in
      79%, and of dust exposure in 54%, most commonly to aluminum, silica and sawdust.
      GM-CSF autoantibody correlated with clinical outcome and KL-6 with diffusing
      capacity. The number of whole lung lavages (WLL) necessary to reach remission was
      higher in current smokers. CONCLUSIONS: This study shows that the use of BAL for
      the diagnosis of PAP can reduce the need of histological confirmation. A history
      of dust or fume inhalation is strongly associated with PAP, also with the
      autoimmune form. Smoking seems to influence the response to treatment, increasing
      the number of WLL necessary to reach remission.

PMID- 21900001
TI  - Probing biomolecular interaction forces using an anharmonic acoustic technique
      for selective detection of bacterial spores.
AB  - Receptor-based detection of pathogens often suffers from non-specific
      interactions, and as most detection techniques cannot distinguish between
      affinities of interactions, false positive responses remain a plaguing reality.
      Here, we report an anharmonic acoustic based method of detection that addresses
      the inherent weakness of current ligand dependant assays. Spores of Bacillus
      subtilis (Bacillus anthracis simulant) were immobilized on a thickness-shear mode
      AT-cut quartz crystal functionalized with anti-spore antibody and the sensor was
      driven by a pure sinusoidal oscillation at increasing amplitude. Biomolecular
      interaction forces between the coupled spores and the accelerating surface caused
      a nonlinear modulation of the acoustic response of the crystal. In particular,
      the deviation in the third harmonic of the transduced electrical response versus
      oscillation amplitude of the sensor (signal) was found to be significant. Signals
      from the specifically-bound spores were clearly distinguishable in shape from
      those of the physisorbed streptavidin-coated polystyrene microbeads. The
      analytical model presented here enables estimation of the biomolecular
      interaction forces from the measured response. Thus, probing biomolecular
      interaction forces using the described technique can quantitatively detect
      pathogens and distinguish specific from non-specific interactions, with potential
      applicability to rapid point-of-care detection. This also serves as a potential
      tool for rapid force-spectroscopy, affinity-based biomolecular screening and
      mapping of molecular interaction networks.

PMID- 21900002
TI  - Colorimetric detection of platelet-derived growth factors through competitive
      interactions between proteins and functional gold nanoparticles.
AB  - We have developed a colorimetric assay-using aptamer modified 13-nm gold
      nanoparticles (Apt-Au NPs) and fibrinogen adsorbed Au NPs (Fib-Au NPs, 56nm)-for
      the highly selective and sensitive detection of platelet-derived growth factors
      (PDGF). Apt-Au NPs and Fib-Au NPs act as recognition and reporting units,
      respectively. PDGF-binding-aptamer (Apt(PDGF)) and 29-base-long thrombin-binding
      aptamer (Apt(thr29)) are conjugated with Au NPs to prepare functional Apt-Au NPs
      (Apt(PDGF)/Apt(thr29)-Au NPs) for specific interaction with PDGF and thrombin,
      respectively. Thrombin interacts with Fib-Au NPs in solutions to catalyze the
      formation of insoluble fibrillar fibrin-Au NPs agglutinates through the
      polymerization of the unconjugated and conjugated fibrinogen. The activity of
      thrombin is suppressed once it interacts with the Apt(PDGF)/Apt(thr29)-Au NPs.
      The suppression decreases due to steric effects through the specific interaction
      of PDGF with Apt(PDGF), occurring on the surfaces of Apt(PDGF)/Apt(thr29)-Au NPs.
      Under optimal conditions [Apt(PDGF)/Apt(thr29)-Au NPs (25pM), thrombin (400pM)
      and Fib-Au NPs (30pM)], the Apt(PDGF)/Apt(thr29)-Au NPs/Fib-Au NPs probe responds
      linearly to PDGF over the concentration range of 0.5-20nM with a correlation
      coefficient of 0.96. The limit of detection (LOD, signal-to-noise ratio=3) for
      each of the three PDGF isoforms is 0.3nM in the presence of bovine serum albumin
      at 100MUM. When using the Apt(PDGF)/Apt(thr29)-Au NPs as selectors for the
      enrichment of PDGF and for the removal of interferences from cell media, the LOD
      for PDGF provided by this probe is 35pM. The present probe reveals that the
      concentration of PDGF in the three cell media is 230 (+/-20)pM, showing its
      advantages of simplicity, sensitivity, and specificity.

PMID- 21900003
TI  - Multiwalled carbon nanotubes dispersed in carminic acid for the development of
      catalase based biosensor for selective amperometric determination of H(2)O(2) and
      iodate.
AB  - We report the preparation of stable dispersion of multiwalled carbon nanotubes
      (MWCNTs) using carminic acid (CA) as a dispersing agent. The transmission
      electron microscopy (TEM), scanning electron microscopy (SEM), and atomic force
      microscopy (AFM) results confirmed that MWCNT is well dispersed in CA aqueous
      solution and CA has been well adsorbed at MWCNT walls. Fourier transform infrared
      (FTIR) and UV-vis absorption spectra results also confirmed the adsorption of CA
      at MWCNT. To develop a highly selective amperometric biosensor for H(2)O(2) and
      iodate, the model enzyme catalase (CAT) was immobilized at CACNT modified glassy
      carbon electrode surface. The immobilized CAT exhibits well defined quasi
      reversible redox peaks at a formal potential (E degrees ') of -0.559V in 0.05M pH
      7 phosphate buffer solution (PBS). The proposed CAT/CACNT biosensor exhibits
      excellent amperometric response towards H(2)O(2) and iodate in the linear
      concentration range between 10MUM to 3.2mM and 0.01-2.16mM. The sensitivity
      values are 287.98MUAmM(-1)cm(-2) and 0.253mAmM(-1)cm(-2), respectively. Moreover,
      the developed CAT biosensor exhibits high affinity for H(2)O(2) and iodate with
      good selectivity.

PMID- 21900004
TI  - Evolution of the Achilles tendon: The athlete's Achilles heel?
AB  - The Achilles tendon is believed to have first developed two million years ago
      enabling humans to run twice as fast. However if the Achilles tendon is so
      important in terms of evolution, then why is this tendon so prone to injury -
      especially for those more active like athletes. The Achilles tendon had an
      integral role in evolving apes from a herbivorous diet to early humans who
      started hunting for food over longer distances, resulting in bipedal locomotion.
      Evolutionary advantages of the Achilles tendon includes it being the strongest
      tendon in the body, having an energy-saving mechanism for fast locomotion, allows
      humans to jump and run, and additionally is a spring and shock absorber during
      gait. Considering these benefits it is therefore not surprising that studies have
      shown athletes have thicker Achilles tendons than subjects who are less active.
      However, contradictory to these findings that show the importance of the Achilles
      tendon for athletes, it is well known that obtaining an Achilles tendon injury
      for an athlete can be career-altering. A disadvantage of the Achilles tendon is
      that the aetiology of its pathology is complicated. Achilles tendon ruptures are
      believed to be caused by overloading the tensed tendon, like during sports.
      However studies have also shown athlete Achilles tendon ruptures to have
      degenerative changes in the tendon. Other flaws of the Achilles tendon are its
      non-uniform vascularity and incomplete repair system which may suggest the
      Achilles tendon is on the edge of evolution. Research has shown that there is a
      genetic influence on the predisposition a person has towards Achilles tendon
      injuries. So if this tendon is here to stay in our anatomy, and it probably is
      due to the slow rate of evolution in humans, research in genetic modification
      could be used to decrease athletes' predisposition to Achilles tendinopathy.

PMID- 21900005
TI  - Carcinoma cuniculatum of foot.

PMID- 21900006
TI  - Seasonal variation in Laminaria digitata and its impact on biochemical conversion
      routes to biofuels.
AB  - Laminaria digitata is a highly prevalent kelp growing off the coast of the UK but
      has rarely been considered as a source of biomass to date. This study shows it
      can be used as a feedstock in both ethanol fermentation and anaerobic digestion
      for methane production. The study optimised several parameters in the
      fermentation of L. digitata and investigated the suitability of the macroalgae
      through the year using samples harvested every month. For both methane and
      ethanol production, minimum yields were seen in material harvested in March when
      the carbohydrates laminarin and mannitol were lowest. July material contained the
      highest combined laminarin and mannitol content and maximum yields of 167 mL
      ethanol and 0.219 m(3) kg(-1)L. digitata.

PMID- 21900007
TI  - Baeyer-Villiger monooxygenases in aroma compound synthesis.
AB  - Baeyer-Villiger monooxygenases (BVMOs) are presented as highly selective and
      efficient biocatalysts for the synthesis of aroma lactones via kinetic resolution
      of 2-substituted cycloketones, exemplified with two delta-valerolactones, the
      jasmine lactones and their epsilon-caprolactone homologs. Analytical scale
      screens of our BVMO library ensued by preparative whole-cell biotransformations
      led to the identification of two enzymes (cyclohexanone monooxygenase from
      Arthrobacter BP2 and cyclododecanone monooxygenase from Rhodococcus SC1)
      perfectly suited for the task at hand: easily accessible racemic starting
      materials were bio-oxidized to almost enantiopure ketones and lactones in good
      yields (48-74%) and optical purities (ee 93% to >99%, E>100).

PMID- 21900008
TI  - Re-evaluating the role of axillary lymph node dissection in screen-detected
      breast cancer patients.
AB  - INTRODUCTION: The American College of Surgeons Oncology Group (ACOSOG), Z0011
      trial, demonstrated that there was no therapeutic benefit from completion
      lymphadenectomy in early stage breast cancer patients with positive sentinel node
      (SLN) biopsy. Patients with asymptomatic screen-detected tumors may represent a
      subgroup where completion axillary dissection with its attendant morbidities is
      unacceptable. Therefore, the aim of this study was to evaluate the role of ALND
      in an asymptomatic screen-detected breast cancer cohort. METHODS: Patients were
      recruited from the national screening program which offers women (aged 50 to 65)
      biannual digital mammography. Over a 1 year period 519 screen-detected breast
      cancer patients were recruited of which 110 had a positive SLN. RESULTS: Of 519
      patients in a national screening program that were clinically/radiologically
      identified as axillary node negative, 110 (21.2%) had a positive SLN. All 110 (T1
      = 68, T2 = 42) patients proceeded to have an axillary clearance. 68 (59%) had T1
      tumors and of these 40 (60%), despite a positive SLN, had no metastatic nodes on
      final pathological analysis of their axilla. In addition, 21 (50%) patients with
      T2 tumors had no metastatic nodes except for a positive SNB. Furthermore, only 6
      (8.8%) of T1 tumors with a positive SLN had 4 or more metastatic axillary lymph
      nodes. CONCLUSION: 55.45% of patients with a screen-detected T1/T2 tumor had
      negative completion lymphadectomy. These findings compel us to re-evaluate the
      role of axillary dissection in the screen-detected asymptomatic breast cancer
      population to avoid unnecessary ALND with its attendant morbidities.

PMID- 21900009
TI  - The ER in 3D: a multifunctional dynamic membrane network.
AB  - The endoplasmic reticulum (ER) is a large, singular, membrane-bound organelle
      that has an elaborate 3D structure with a diversity of structural domains. It
      contains regions that are flat and cisternal, ones that are highly curved and
      tubular, and others adapted to form contacts with nearly every other organelle
      and with the plasma membrane. The 3D structure of the ER is determined by both
      integral ER membrane proteins and by interactions with the cytoskeleton. In this
      review, we describe some of the factors that are known to regulate ER structure
      and discuss how this structural organization and the dynamic nature of the ER
      membrane network allow it to perform its many different functions.

PMID- 21900010
TI  - Compartmentalization of the nucleus.
AB  - The nucleus is a spatially organized compartment. The most obvious way in which
      this is achieved is at the level of chromosomes. The positioning of chromosomes
      with respect to nuclear landmarks and with respect to each other is both non
      random and cell-type specific. This suggests that cells possess molecular
      mechanisms to influence the folding and disposition of chromosomes within the
      nucleus. The localization of many proteins is also heterogeneous within the
      nucleus. Therefore, chromosome folding and the localization of proteins leads to
      a model in which individual genes are positioned in distinct protein environments
      that can affect their transcriptional state. We focus here on the spatial
      organization of the nucleus and how it impacts upon gene expression.

PMID- 21900011
TI  - Impact of stroke on anterior-posterior force generation prior to seat-off during
      sit-to-walk.
AB  - Force generation during sit-to-walk (STW) post-stroke is a poorly studied area,
      although STW is a common daily transfer giving rise to a risk of falling in
      persons with disability. The purpose of this study was to describe and compare
      strategies for anterior-posterior (AP) force generation prior to seat-off during
      the STW transfer in both subjects with stroke and in matched controls. During STW
      at self-selected speed, AP force data were collected by 4 force plates, beneath
      the buttocks and feet from eight subjects with stroke (>6 months after onset) and
      8 matched controls. Subjects with post-stroke hemiparesis and matched controls
      generated a similar magnitude of total AP force impulses (F(1,71)=0.67; p=0.42)
      beneath buttocks and feet prior to seat-off during STW. However, there were
      significant group differences in AP force impulse generation beneath the stance
      buttock (i.e. the non-paretic buttock in the stroke group), with longer duration
      (F(1,71)=8.78; p<0.005), larger net AP impulse (F(1,71)=6.76; p<0.05) and larger
      braking impulse (F(1,71)=7.24; p<0.05) in the stroke group. The total braking
      impulse beneath buttocks and feet was about 4.5 times larger in the stroke group
      than in the control group (F(1,71)=8.84; p<0.005). An intra- and inter-limb dys
      coordination with substantial use of braking impulses was demonstrated in the
      stroke group. This motor strategy differed markedly from the smooth force
      interaction in the control group. These results might be important in the
      development of treatment models related to locomotion post-stroke.

PMID- 21900012
TI  - Recurrence quantification analysis of gait in normal and hypovestibular subjects.
AB  - The study of postural control processes during locomotion may provide useful
      outcome measures of stability for people with unilateral vestibular hypofunction
      (UVH). Since nonlinear analysis techniques can characterize complex behaviour of
      a system, this may highlight mechanisms underlying dynamic stability in
      locomotion, although only few efforts have been made. In particular, there have
      been no studies that use recurrence quantification analysis (RQA), which can be
      applied even to short and non-stationary data. The purpose of this study was to
      develop a new method for walking balance assessment measuring the complexity of
      head, trunk and pelvis three-dimensional accelerations and angular velocities
      during normal overground locomotion by means of RQA in normal subjects and UVH
      patients. The results showed differential effect of upper body parts on pattern
      regularity, with better head than pelvis stabilization in both groups of
      subjects. The RQA outputs such as percent determinism and recurrence were
      nevertheless significantly lower in the UVH group for all measures, suggesting
      that body accelerations and angular velocities, although not significantly
      different in amplitude, were more chaotic in patients. The observed lower
      regularity of upper body movements in UVH is consistent with an important role of
      the vestibular system in controlling dynamic stability during walking. The
      findings suggest that RQA can be used as a quantitative tool to assess walking
      performance and rehabilitation outcome in patients with different balance
      disorders.

PMID- 21900014
TI  - Ultra-structure and histochemistry of digestive cells of Podisus nigrispinus
      (Hemiptera: Pentatomidae) fed with prey reared on bt-cotton.
AB  - The toxic effects of Bt proteins from the body of the prey/host to predators and
      parasitoids have been investigated as a route of impact on non-target insects of
      Bt crops. This research aimed to analyze ultrastructural changes and
      histochemistry in digestive cells of the middle region of the midgut of Podisus
      nigrispinus fed, since its second instar, with Spodoptera frugiperda reared on Bt
      cotton variety Acala90 B, which expresses the toxin Cry 1Ac, and its non-Bt
      isoline Acala 90. Fragments of the midgut of P. nigrispinus were analyzed by
      electron microscopy. For the histochemical analysis, Bromophenol Blue, Periodic
      Acid Schiff von Kossa, Alcian Blue pH 2.5 and Sudan Black were used. The Cry1Ac
      toxin of Bt cotton ingested by S. frugiperda promotes a disorganization in the
      perimicrovillar matrix of P. nigrispinus (third trophic level), thus generating
      ultrastructural changes in the digestive cells, as elongation of microvilli,
      presence of spherocrystals and granules of different electron densities, in
      addition to altering the distribution pattern of glycogen, lipids and calcium of
      these cells in the median region of the midgut. Thus, we conclude that species
      moderately susceptible to Cry1Ac toxin, such as S. frugiperda, can acquire this
      toxin and expose it to P. nigrispinus, which can interfere with your ability to
      predation.

PMID- 21900013
TI  - New aporphinoid 5-HT2A and alpha1A antagonists via structural manipulations of
      nantenine.
AB  - A series of C1, C2, C3 and N6 analogs of nantenine (2) was synthesized and
      evaluated in 5-HT(2A) and alpha(1A) receptor functional assays. Alkyl
      substitution of the C1 and N6 methyl groups of nantenine provided selective 5
      HT(2A) and alpha(1A) antagonists, respectively. The C2 alkyloxy analogs studied
      were generally selective for alpha(1A) versus 5-HT(2A). The C3 bromo analog 15 is
      one of the most potent aporphinoid 5-HT(2A) antagonists known presently.

PMID- 21900015
TI  - Liquid scintillation based quantitative measurement of dual radioisotopes (3H and
      45Ca) in biological samples for bone remodeling studies.
AB  - Acute and prolonged bone complications associated with radiation and chemotherapy
      in cancer survivors underscore the importance of establishing a laboratory-based
      complementary dual-isotope tool to evaluate short- as well as long-term bone
      remodeling in an in vivo model. To address this need, a liquid scintillation dual
      label method was investigated using different scintillation cocktails for
      quantitative measurement of (3)H-tetracycline ((3)H-TC) and (45)Ca as markers of
      bone turnover in mice. Individual samples were prepared over a wide range of
      known (45)Ca/(3)H activity ratios. Results showed that (45)Ca/(3)H activity
      ratios determined experimentally by the dual-label method were comparable to the
      known activity ratios (percentage difference ~2%), but large variations were
      found in samples with (45)Ca/(3)H activity ratios in range of 2-10 (percentage
      difference ~20-30%). Urine and fecal samples from mice administered with both
      (3)H-TC and (45)Ca were analyzed with the dual-label method. Positive
      correlations between (3)H and (45)Ca in urine (R=0.93) and feces (R=0.83)
      indicate that (3)H-TC and (45)Ca can be interchangeably used to monitor
      longitudinal in vivo skeletal remodeling.

PMID- 21900016
TI  - Feasibility study for production of I-131 radioisotope using MNSR research
      reactor.
AB  - A feasibility study for (131)I production using a Low Power Research Reactor was
      conducted to predict the yield of (131)I by cyclic activation technique. A
      maximum activity of 5.1GBq was achieved through simulation using FORTRAN 90, for
      an irradiation of 6h. But experimentally only 4h irradiation could be done, which
      resulted in an activity of 4.0*10(5)Bq. The discrepancy in the activities was due
      to the fact that beta decays released during the process could not be considered.

PMID- 21900017
TI  - Does lung ischemia and reperfusion have an impact on coronary flow? A
      quantitative coronary blood-flow analysis with inflammatory cytokine profile.
AB  - OBJECTIVE: Ischemia-reperfusion (IR) injury remains a major cause of early
      morbidity and mortality after lung transplantation with poorly documented
      extrapulmonary repercussions. To determine the hemodynamic effect due to lung IR
      injury, we performed a quantitative coronary blood-flow analysis in a swine model
      of in situ lung ischemia and reperfusion. METHODS: In 14 healthy pigs, blood flow
      was measured in the ascending aorta, left anterior descending (LAD), circumflex
      (Cx), right coronary artery (RCA), right common carotid artery (RCCA), and left
      internal mammary artery (LIMA), along with left-and right-ventricular pressures
      (LVP and RVP), aortic pressure (AoP), and pulmonary artery pressure (PAP).
      Cardiac Troponin (cTn), interleukin 6 and 10 (IL-6 and IL-10), and tumor necrosis
      factor A (TNF-A) were measured in coronary sinus blood samples. The experimental
      (IR) group (n=10) underwent 60 min of lung ischemia followed by 60 min of
      reperfusion by clamping and releasing the left pulmonary hilum. Simultaneous
      measurements of all parameters were made at baseline and during IR. The control
      group (n=4) had similar measurements without lung IR. RESULTS: In the IR group,
      total coronary flow (TCF=LAD+Cx+RCA blood-flow) decreased precipitously and
      significantly from baseline (113+/-41 ml min"1) during IR (p<0.05), with the
      lowest value observed at 60 min of reperfusion (-37.1%, p<0.003). Baseline cTn
      (0.08+/-0.02 ng ml(-1)) increased during IR and peaked at 45 min of reperfusion
      (+138%, p<0.001). Baseline IL-6 (9.2+/-2.17 pg ml(-1)) increased during IR and
      peaked at 60 min of reperfusion (+228%, p<0.0001). Significant LVP drop at 5 min
      of ischemia (p<0.05) was followed by a slow return to baseline at 45 min of
      ischemia. A second LVP drop occurred at reperfusion (p<0.05) and persisted.
      Conversely, RVP increased throughout ischemia (p<0.05) and returned toward
      baseline during reperfusion. Coronary blood flow and hemodynamic profile remained
      unchanged in the control group. IL-10 and TNF-A remained below the measurable
      range for both the groups. CONCLUSIONS: In situ lung IR has a marked negative
      impact on coronary blood flow, hemodynamics, and inflammatory profile. In
      addition, to the best of our knowledge, this is the first study where coronary
      blood flow is directly measured during lung IR, revealing the associated
      increased cardiac risk.

PMID- 21900018
TI  - Placement of Alfieri's suture.

PMID- 21900019
TI  - Reappraisal of a 20-year experience with the radial artery as a conduit for
      coronary bypass grafting.
AB  - OBJECTIVE: This study aimed at evaluating the clinical and angiographic results
      of the radial artery (RA) used as a coronary bypass graft over 20 years. METHODS:
      Clinical follow-up was obtained in 563 patients at 9.2 years. Angiographic follow
      up was obtained in 351 patients with opacification of 1427 conduits, including
      629 RA at 7.0 years. RESULTS: At 9.2 years, freedom from overall and
      cardiovascular death was 80.3% and 92.7%, respectively. Symptoms were: acute
      myocardial infarction: 2.1% (n=12); angina: 17.4% (n=98), and congestive heart
      failure 10.6% (n=60). Percutaneous revascularization was required in 13.5% (n=76)
      of cases on: native coronary (n=77), RA conduit (n=21), and other graft (n=7).
      Reoperation was needed in 2.3% (n=13) of cases for valve replacement (n=10) and
      redo coronary artery bypass grafting (CABG) (n=3). At 7.0 years, RA patency was
      82.8% (521/629) and was lower than that of left internal mammary artery (IMA),
      95.5% (491/514) (p<0.001); similar to right IMA, 87.9% (51/58, p=0.32); free IMA,
      80.0% (44/55, p=0.60); and vein, 81.9% (140/171, p=0.77). RA patency was lower in
      the case of myocardial ischemia: 74.0% (174/235) versus 88.1% (347/394) in
      asymptomatics (p<0.001). RA patency was higher for diagonal (93.1% (95/102))
      compared to circumflex (82.5% (274/332, p<0.01)) and right coronary (77.6%
      (146/188, p<0.001)). Calcium channel blockers had no impact on RA patency.
      Separating four groups at successive follow-up intervals, RA patency was: 86.2%,
      81.9%, 81.4%, and 81.6% at 1.0, 5.4, 8.3, and 13.1 years, respectively.
      CONCLUSION: CABG with the RA offered long-lasting clinical benefit. Beyond the
      first postoperative year during which some attrition was observed, RA patency was
      remarkably stable for up to 20 years.

PMID- 21900021
TI  - Tackling reperfusion injury after cardiopulmonary bypass with
      tetrahydrobiopterin: new therapeutic potentials for this phenylketonuria drug?

PMID- 21900022
TI  - Extracorporeal membrane oxygenation support improves survival of patients with
      Hantavirus cardiopulmonary syndrome refractory to medical treatment.
AB  - OBJECTIVE: The aim of the study was to evaluate the outcome of extracorporeal
      membrane oxygenation (ECMO) support in Hantavirus cardiopulmonary syndrome (HCPS)
      patients with a predicted mortality of 100%, and the complications associated
      with this treatment modality and different cannulation techniques. METHODS: A
      total of 51 patients with refractory HCPS were supported with ECMO between April
      1994 and June 2010. They were divided into group A consisting of the 26 patients
      treated between 1994 and 2000 and group B consisting of 25 patients treated
      between 2003 and 2010. No patients were treated between September 2000 and
      December 2003. Patients in group A were intubated when they became hypoxic and
      placed on ECMO when they became hemodynamically unstable, whereas patients in
      group B had elective insertion of vascular sheaths and were almost concurrently
      intubated and placed on ECMO when they decompensated. Cannulation of the femoral
      vessels was performed percutaneously in 18 (35.3%) patients and with an open
      technique in 33 (64.7%) patients. RESULTS: Complications from percutaneous
      cannulation occurred in 4/18 (22.27%) patients: retroperitoneal hematoma in 2/18
      (11.1%) and lower-extremity ischemia in 2/18 (11.1%) patients. Complications from
      open femoral cannulation occurred in 12/33 (36.3%) patients: bleeding in 10/33
      (30.3%) patients and ischemia in 2/33 (6.1%) patients. The overall survival was
      66.6% (34 of 51 patients); 56% (14/26) for group A and 80% (20/25) for group B (p
      = 0.048). There was no difference in mortality regarding the method of
      cannulation. A trend toward increased mortality in patients with cannulation
      complications was recognized, but it was not statistically significant. Mortality
      was not associated with ECMO duration (average 121.7h, range: 5-276h). All
      survivors recovered and were discharged from the hospital after a mean hospital
      stay of 19.8 days (range: 10-39 days). CONCLUSIONS: Two-thirds of 51 HCPS
      patients with a predicted mortality of 100%, who were supported with ECMO,
      survived and recovered completely. Survival was significantly higher in the
      second half of the study. Complications associated with both types of femoral
      cannulation were associated with a trend toward decreased survival, which was not
      significant.

PMID- 21900024
TI  - Health care reform: what does it mean for people living with HIV infection?

PMID- 21900023
TI  - Is it safe to include octogenarians at the start of a video-assisted thoracic
      surgery lobectomy programme?
AB  - OBJECTIVE: The study aimed to investigate the safety of including patients >= 80
      years of age at the start of a video-assisted thoracic surgery major pulmonary
      resection (VMPR) programme. METHODS: Patients were considered for VMPR if the
      computed tomography/positron emission tomography (CT/PET) was suggestive of T1-3,
      N0-1 and M0 lesion. Age was not a criterion for exclusion at the very start of
      the programme. Data were collected prospectively and comparison made between two
      groups, (A) <80 years of age and (B) >= 80 years, in terms of preoperative risk
      factors, oncological and functional data, operative results, postoperative
      complications and survival. RESULTS: Between April 2005 and January 2011, 200
      consecutive patients were considered for VMPR. A total of 160 had non-small-cell
      lung cancer, of whom 136 were in group A, with a median age of 66.5 (range: 42.8
      79.4 years) and 24 in group B with a median age of 82 (range: 80-85.5 years). In
      group B, 13 were men and 11 were women. Rate of conversion to thoracotomy was
      similar (3 (12.5%) in group B vs 17 (12.5%) in group A, p = 0.65), and so was the
      mean hospital stay (5.8 +/- 3.3 days in group B vs 5.9 +/- 4.6 days in group A, p
      = 0.899). Admission to intensive care unit and atrial fibrillation were
      significantly higher in octogenarians (six (25%) and six (25%) in group B vs
      eight (5.9%) and nine (6.6%) in group A, p = 0.008 and p = 0.012, respectively).
      There was significantly less mean days of air leak in octogenarians (0.06 +/- 0.3
      days in group B vs 2.8 +/- 5.6 days in group A, p = 0.000). Otherwise, there were
      no age-related differences in relation to morbidity, mortality and the 3-year
      survival rate. CONCLUSION: Octogenarians undergoing VMPR have a higher incidence
      of atrial fibrillation and admission to the intensive care unit for
      cardiopulmonary support but otherwise are no different from younger age groups
      when it comes to rate of conversion to thoracotomy, hospital stay, morbidity and
      mortality. Age should not be an excuse to deny the elderly curative VATS
      resection. In our experience, accepting octogenarians early in the VMPR programme
      did not compromise the outcome results.

PMID- 21900025
TI  - Social and family characteristics of Hispanics with epilepsy.
AB  - The purpose of this study is to determine how acculturation, social support,
      family emotional involvement, perceived family criticism and stigma are
      associated with epilepsy self-efficacy and depression. A principal components
      analysis (PCA) was used to describe the salience of these characteristics within
      a sample of Hispanics with epilepsy. A total of 50 Hispanic adults of Mexican
      descent identified in our Epilepsy Clinic participated in this study. The PCA
      identified four distinct types, two were relatively culture-free, and two were
      distinctly culturally oriented. The first non-culture affiliated type described a
      well-adjusted group of individuals that tended to be males with moderate self
      efficacy, who received social support, and who were unlikely to have depression
      or feel stigmatized. The second non-culture affiliated type described a dimension
      in which family emotional involvement tended to co-occur with perceived
      criticism. The Anglo-oriented group had a family environment that did not appear
      to criticize the individual with epilepsy and had good self-efficacy. The Mexican
      oriented group had high self-efficacy and was unlikely to have depression.
      Results suggest that acculturation variables must be taken into consideration
      among ethnic groups because social, psychological and acculturation variables
      interact in complex ways. Additionally, it is clear that a diagnosis of epilepsy
      does not automatically lead to poor quality of life, stigma, or depression.

PMID- 21900026
TI  - Enhancement of antibacterial activity of tilmicosin against Staphylococcus aureus
      by solid lipid nanoparticles in vitro and in vivo.
AB  - This study aimed to enhance the antibacterial activity of tilmicosin by solid
      lipid nanoparticles (SLN). Tilmicosin-loaded hydrogenated castor oil (HCO)-SLN
      was prepared using a hot homogenisation and ultrasonication method. The
      physicochemical characteristics of SLN were investigated by scanning electron
      microscopy (SEM) and photon correlation spectroscopy (PCS). The antibacterial
      activity of tilmicosin-SLN against Staphylococcus aureus was evaluated by growth
      inhibition and colony-counting method. A therapeutic study of tilmicosin-SLN was
      conducted by subcutaneous injection in a mouse mastitis model infected with S.
      aureus by teat canal infusion. Therapeutic efficacy was assessed by physical
      appearance of the mammary gland and measurement of colony-forming units (CFU) per
      gland. The results showed that the diameter, polydispersivity index, zeta
      potential, encapsulation efficiency and loading capacity of the nanoparticles
      were 343+/-26 nm, 0.33+/-0.08, -7.9+/-0.4 mV, 60.4+/-3.3% and 11.2+/-0.47%,
      respectively. Tilmicosin-SLN showed a sustained-release effect and sustained and
      enhanced antibacterial activity in vitro. SLN significantly enhanced the
      therapeutic efficacy of tilmicosin determined by lower CFU counts and a decreased
      degree of inflammation. These results demonstrated that the HCO-SLN is an
      effective carrier to enhance the antibacterial activity of tilmicosin.

PMID- 21900027
TI  - New modeling of scattering behaviors of argon atoms on tungsten substrate.
AB  - In this study argon beam-tungsten surface scattering processes were investigated
      numerically by applying molecular dynamics simulations. Energy transfer, momentum
      change and the scattering processes of argon gas atoms from the W(110) surface
      were discussed. The molecular dynamics results showed that Maxwell boundary
      conditions fail to describe the behaviors of a high mean kinetic energy argon
      beam impinging on a tungsten surface. A new three-dimensional model of argon
      tungsten interaction was thus proposed, and its results proved to be in line with
      experimental and theoretical results that have been obtained previously by other
      researchers. Specifically, we developed a method for the normalization of the
      parameters of a gas beam scattered by a metal surface. We found that the ratio of
      the average velocity of the scattered beam to the appropriate root mean square
      deviation (RMSD) allowed us to determine whether the distribution of the
      scattered atoms was Maxwellian or not. We found that the shape of the functions
      representing the angular distributions of the scattered Ar atoms could be
      determined using the ratio of the RMSD of an angle (azimuthal or polar) of the
      scattered beam to the RMSD of a uniform distribution. The distribution of the
      azimuthal angle of the scattered atoms was found to be uniform regardless of the
      incident's kinetic energy, when the incident of the beam on the surface was
      normal.

PMID- 21900028
TI  - Evaluation of auditory function in a population of clinically healthy cats using
      evoked otoacoustic emissions.
AB  - Cats may demonstrate deafness due to a variety of aetiologies and the current
      preferred method for assessing auditory function is the brainstem auditory evoked
      response (BAER). The BAER has largely been replaced by otoacoustic emission (OAE)
      testing in human neonatal deafness screening as the equipment is more readily
      available, is cheaper and the test is less invasive and simpler. This is the
      first study to demonstrate that transient evoked OAEs (TEOAE) and distortion
      product OAEs (DPOAE) can be recorded in cats using commercially available
      equipment. Protocols for recording the emissions and analysing the results are
      given. DPOAE testing is suggested to be quicker in this population of healthy
      cats and shows promise in rapidly providing detailed information about auditory
      function at a variety of different frequencies.

PMID- 21900029
TI  - Clinical use of cyclosporine as an adjunctive therapy in the management of feline
      idiopathic pure red cell aplasia.
AB  - The clinical use of cyclosporine is described in a group of client-owned cats
      diagnosed with idiopathic pure red cell aplasia (PRCA). All 10 cats were treated
      with combinations of glucocorticoids and cyclosporine. Of the 10 cats, the eight
      for which follow-up data was available achieved and maintained remission for a
      median of 31 and 406 days, respectively. Therapy was reduced or discontinued in
      7/8 cats; 2/7 maintained remission off therapy and 5/7 cats relapsed. Remission
      was reinduced in four cats, with 3/4 cats maintained long-term on low dose
      therapy. Adverse effects associated with cyclosporine therapy were responsive to
      dose reduction or drug withdrawal. Feline idiopathic PRCA was responsive to
      combination immunosuppressive therapy with glucocorticoids and cyclosporine.
      Relapse was common, particularly after drug discontinuation; therefore, most cats
      required maintenance long-term low dose therapy.

PMID- 21900030
TI  - The effects of adding group-based lifestyle counselling to individual counselling
      on changes in plasma glucose levels in a randomized controlled trial: the Inter99
      study.
AB  - AIM: This study aimed to assess whether group-based lifestyle counselling offered
      to a high-risk population subgroup had any effect beyond individual
      multifactorial interventions on fasting plasma glucose (FPG) and 2-h plasma
      glucose (2hPG) changes. METHODS: In a population-based study of 6784
      participants, 4053 were determined to be at high risk based on a risk estimate of
      ischaemic heart disease or the presence of risk factors (smoking, hypertension,
      hypercholesterolaemia, obesity, impaired glucose tolerance). Of these subjects,
      90% were randomized to high-intensity intervention (group A) and 10% to low
      intensity intervention (group B). All participants went through health
      examinations, risk assessments and individual lifestyle counselling. Participants
      in group A were further offered group-based lifestyle counselling. The
      intervention was repeated after 1 and 3 years. A total of 2738 participants free
      of diabetes at baseline (1999-2001) and with at least one FPG and/or 2hPG
      measurement during 5 years of follow-up were included in the analyses.
      Differences in changes of plasma glucose between groups A and B were analyzed
      using multilevel linear regression. RESULTS: For FPG, crude 5-year changes were
      significantly different between the two groups (group A: -0.003 mmol/L vs group
      B: -0.079 mmol/L; P=0.0427). After adjusting for relevant confounders, no
      differences in FPG changes were observed (P=0.116). Also, no significant
      differences in the 5-year changes in 2hPG between the two groups were observed
      (group A: - 0.127 mmol/L vs group B: -0.201 mmol/L; P=0.546). CONCLUSION:
      Offering additional group-based intervention to a high-risk population subgroup
      had no clinical effects on changes in plasma glucose beyond those of
      individualized multifactorial interventions.

PMID- 21900031
TI  - High regioselective ultrasonic-assisted synthesis of 2,7-diaryl-4,7
      dihydropyrazolo[1,5-a]pyrimidine-5-carboxylic acids.
AB  - New and high regioselective method of the synthesis of 2,7-diaryl-4,7
      dihydropyrazolo[1,5-a]pyrimidine-5-carboxylic acids by reaction of 3-aryl-5
      aminopyrazoles with arylidenpyruvic acid at room temperature under
      ultrasonication was developed and discussed.

PMID- 21900032
TI  - An examination of the mechanical properties of the annulus fibrosus: the effect
      of vibration on the intra-lamellar matrix strength.
AB  - Vibration has been associated with low back pain and disc herniation; however the
      mechanism responsible for this association is unclear. It is theorized that
      herniation propagates through annular layers via clefts that form in the
      extracellular matrix between collagen fibres (intra-lamellar matrix) within each
      lamella. The effect of cyclic compressive loading at 5 Hz, applied to porcine
      functional spine units, on the mechanical properties of excised single annular
      lamellae was examined. These lamellae were tested under tension applied
      perpendicular to the collagen fibre orientation, effectively isolating the intra
      lamellar matrix. Vibration affected the deformation magnitude at the end of the
      toe region of the stress-stretch ratio curve; specifically vibrated tissues
      showed larger toe regions (stretch ratio of 1.50 as compared to 1.31 observed in
      the control tissues, p=0.027). It is hypothesized that this result may be due to
      damaged elastin-a protein responsible for minimizing deformation and assisting
      with returning tissues to normal length following tension.

PMID- 21900033
TI  - Genetic variant of HTR2A associates with risk of impulse control and repetitive
      behaviors in Parkinson's disease.
AB  - OBJECTIVES: To determine the role of a serotonin 2A receptor gene (=HTR2A)
      variant in the development of impulse control and repetitive behaviors in
      Parkinson's disease. METHODS: We performed a genetic association analysis to a
      cohort of 404 Korean patients with Parkinson's disease who had been enrolled in a
      previous study. Presence of impulse control and repetitive behaviors was screened
      using modified version of Minnesota Impulsive Disorders Interview and genotyping
      for HTR2A c.102T > C was performed using the TaqMan assay. RESULTS: The T allele,
      which is presumably linked to higher receptor expression, was marginally
      associated with impulse control and repetitive behaviors in Parkinson's disease;
      the genetic influence was significantly enhanced in the lower levodopa-equivalent
      dose group, increasing the risk by 2.8 and 6.9 times in CT and TT carriers,
      respectively (p-trend = 0.011). There was no significant interaction between the
      c.102T > C variant and clinical risk variables such as sex, age at onset, total
      daily levodopa-equivalent-dose, use of dopamine agonist and daily dose of
      dopamine agonist. CONCLUSION: Our data support a possible contribution of genetic
      variation in the HTR2A to the susceptibility to impulse control and repetitive
      behaviors in Parkinson's disease.

PMID- 21900034
TI  - School sport policy and school-based physical activity environments and their
      association with observed physical activity in middle school children.
AB  - Empirical research on the effects of school sport policies on children's physical
      activity is limited. This study examined sport policies (intramural vs. varsity),
      physical settings within schools, and supervision in relation to physical
      activity using the System for Observing Play and Leisure in Youth (SOPLAY). Data
      were collected on physical activity levels of children in four middle schools.
      Regression analyses assessed the main effects of sport policy, type of physical
      activity setting, and supervision as well as interactions. Regression models were
      stratified by gender. Children in intramural schools were more likely to use
      indoor spaces and be boys. Regression models indicated that varsity sport
      programs were associated with lower physical activity levels among boys but not
      girls. Significant associations between type of physical activity settings and
      physical activity levels were observed only for boys. Adult supervision was not
      associated with children's physical activity levels. Finally, descriptive results
      showed athletic facilities were under-utilized in all schools.

PMID- 21900035
TI  - Nutritious crops producing multiple carotenoids--a metabolic balancing act.
AB  - Plants and microbes produce multiple carotenoid pigments with important
      nutritional roles in animals. By unraveling the basis of carotenoid biosynthesis
      it has become possible to modulate the key metabolic steps in plants and thus
      increase the nutritional value of staple crops, such as rice (Oryza sativa),
      maize (Zea mays) and potato (Solanum tuberosum). Multigene engineering has been
      used to modify three different metabolic pathways simultaneously, producing maize
      seeds with higher levels of carotenoids, folate and ascorbate. This strategy may
      allow the development of nutritionally enhanced staples providing adequate
      amounts of several unrelated nutrients. By focusing on different steps in the
      carotenoid biosynthesis pathway, it is also possible to generate plants with
      enhanced levels of several nutritionally-beneficial carotenoid molecules
      simultaneously.

PMID- 21900036
TI  - Combination therapies for combating antimicrobial resistance.
AB  - New drug development strategies are needed to combat antimicrobial resistance.
      The object of this perspective is to highlight one such strategy: treating
      infections with sets of drugs rather than individual drugs. We will highlight
      three categories of combination therapy: those that inhibit targets in different
      pathways; those that inhibit distinct nodes in the same pathway; and those that
      inhibit the very same target in different ways. We will then consider examples of
      naturally occurring combination therapies produced by micro-organisms, and
      conclude by discussing key opportunities and challenges for making more
      widespread use of drug combinations.

PMID- 21900037
TI  - Fe (III) complexes of a bis-benzimidazolyl diamide ligand: spectral and catalytic
      studies.
AB  - A new tetradentate bis benzimidaozlyl diamide ligand N,N'-Bis (benzimidazol-2-yl
      methyl)-hexane-1,6-dicarboxamide (GBSA) has been synthesized and utilized to
      prepare new Fe(III) complexes with exogenous anionic ligand X=Cl(-) and NO(3)(-).
      Isomer shift values are in the range found for Iron in the +3 oxidation state
      while Quadrupole Splitting indicates large distortion from a six coordinate
      geometry, a finding supported by low temperature EPR work. The E(1/2) values are
      found to be quite cathodic indicating stability of the Iron (III) complexes. The
      oxidation of alcohols was investigated using [Fe(GBSA)Cl(3)] as the catalyst with
      TBHP as an alternate source of oxygen. The respective carbonyl products have been
      isolated and characterized by (1)H NMR, electronic spectroscopy, mass and IR
      spectral studies.

PMID- 21900038
TI  - Effect of inclusion complexation on the photophysical behavior of diphenylamine
      in beta-cyclodextrin medium: a study by electronic spectra.
AB  - Spectral characteristics of diphenylamine (DPA) have been investigated in beta
      cyclodextrin (beta-CDx) solution. The formation of the complex was revealed by
      UV, steady state and time-resolved fluorescence spectroscopy. The stoichiometry
      of DPA:beta-CDx complex, determined using Benesi-Hildebrand equation and Job's
      continuous variation method is 1:1. The binding constants calculated from various
      methods are reported. This inclusion complex formation from DPA and beta-CDx was
      also confirmed by the FT-IR spectral study and SEM image analysis of solid
      complex prepared by co-precipitation method.

PMID- 21900040
TI  - Lytic and latent EBV gene expression in transplant recipients with and without
      post-transplant lymphoproliferative disorder.
AB  - BACKGROUND: Epstein-Barr virus (EBV) is associated with post-transplant
      lymphoproliferative disorder (PTLD), which has significant morbidity and
      mortality in transplant recipients. To devise prophylactic measures, we need
      predictors of PTLD and a better understanding of the physiopathogenesis of the
      disease. OBJECTIVES: To identify a molecular pattern of EBV gene products in
      blood that is specific to PTLD and can be used for the diagnosis of this disease.
      STUDY DESIGN: We evaluated the ratio between latent and replicating EBV nucleic
      acids in individuals with PTLD by comparison with transplant recipients without
      PTLD and immunocompetent hosts with EBV DNA-emia. Subjects were prospectively
      identified between July 2009 and October 2010 at the University of Colorado
      Hospital. EBV DNA, LMP-2A Latency III and BZLF1 Lytic genes mRNA were quantified
      using real-time PCR. RESULTS: We found that PTLD subjects (N = 7) had
      significantly higher EBV DNA-emia compared with non-transplant immunocompetent
      subjects (N = 69; p<0.0001), and transplant recipients without PTLD (N = 105;
      p<0.0001). The ratios between LMP-2A and BZLF1 mRNA in transplant recipients were
      significantly lower than in non-transplant subjects (p = 0.04). However, PTLD and
      non-PTLD transplant recipients displayed similar ratios. CONCLUSIONS: These
      results suggest that EBV replication makes a larger contribution to the
      circulating EBV DNA in transplant recipients compared with immunocompetent hosts.
      Transplant recipients seem to lose control over EBV replication, which may
      contribute to the development of PTLD.

PMID- 21900039
TI  - Cytomegalovirus DNA stability in EDTA anti-coagulated whole blood and plasma
      samples.
AB  - BACKGROUND: Cytomegalovirus (CMV) DNA viral load testing is routinely performed
      in centers that serve patients that are immunosuppressed from organ or
      hematopoietic stem cell transplantation. Clinical laboratories that offer this
      testing often face practical concerns about the storage of these specimens to
      ensure accurate measurement for patient care. The published studies that assess
      CMV DNA stability at 4 degrees C have done so only up to 72 h. OBJECTIVE: Our
      objective was to determine the stability of CMV DNA in whole blood and plasma for
      clinical viral load testing over a 14 day period. STUDY DESIGN: Twenty-one plasma
      samples that were CMV-positive and twenty whole blood samples (including eleven
      CMV-negative whole blood samples spiked with CMV-positive plasma) were stored at
      4 degrees C and underwent extraction and amplification at 3 time points: Day 0,
      Day 7, and Day 14. RESULTS: Log(10) values were calculated and t-test was
      performed on the values comparing Day 0 to Day 14 for plasma and whole blood.
      There was no statistically significant difference between Day 0 and Day 14 for
      both specimen types, including the CMV-negative whole blood specimens that were
      spiked with CMV-positive plasma. CONCLUSIONS: CMV DNA in plasma and whole blood
      is stable for 14 days at a temperature of 4 degrees C.

PMID- 21900041
TI  - Cell aggregation is negatively regulated by N-acylhomoserine lactone-mediated
      quorum sensing in Pantoea ananatis SK-1.
AB  - Pantoea ananatis SK-1 produces N-acylhomoserine lactones (AHLs) and regulates
      expression of some virulence factors through AHL-mediated quorum sensing. In this
      study, we discovered that the strain SK-02I, which has a disrupted AHL-synthetic
      gene, showed constitutive cell aggregation. SK-1 has the ability to aggregate,
      and cell aggregation inhibitory factors are expressed under control of AHL
      mediated quorum sensing. One of the transposon mutants, SK-33M, constitutively
      aggregates without defective AHL production. A homology search revealed that the
      transposon integration site was located in the adhesin-like yeeJ gene. Based on
      RT-PCR analysis, transcription of yeeJ is regulated by AHL-mediated quorum
      sensing. However, because both the wild-type and SK-33M strains induced necrotic
      symptoms in onion leaves, we conclude that the yeeJ gene is not involved in the
      pathogenicity of SK-1.

PMID- 21900042
TI  - Personalized assessment of oxidative cellular damages associated with diabetes
      using erythrocytes adhesion assay.
AB  - Increased generation of reactive oxygen species (ROS) is recognized as a
      prominent feature of vascular dysfunction with diabetes. For self-monitoring of
      the risk of diabetic complications, we proposed a simple adhesion test of
      erythrocytes using positively charged surfaces and its adhesion property was
      found to correlate HbA(1c) level in diabetic patients.

PMID- 21900043
TI  - Disinfection aboard cruise liners and naval units: formation of disinfection by
      products using chlorine dioxide in different qualities of drinking water.
AB  - The world-wide deployment of cruise liners and naval units has caused an
      increased need for the disinfection of drinking water. The main cause for this is
      the unknown quality of drinking water in foreign harbours--besides the formation
      of bio-films due to the climatically disadvantageous conditions in the
      operational area. Water conduits on board are currently disinfected with calcium
      hypochlorite in case of microbiological contamination. Chemical and physical
      analyses after disinfection with calcium hypochlorite have shown that organic by
      products consisting of trihalomethanes develop in considerable amounts during
      disinfection. Furthermore, the method is susceptible to handling errors and thus
      often leads to insufficient disinfection results. Hitherto, the use of other
      disinfection methods allowed by government regulations, especially chlorine
      dioxide, is not widely spread. Unlike disinfection with calcium hypochlorite,
      chlorine dioxide does not lead to the formation of trihalomethanes. Typical
      disinfection by-products (DBP) are the anions chlorite and chlorate, which are
      formed in oxidative processes. The formation conditions of these anions have not
      yet been elucidated. For this reason, the probability of the generation of
      inorganic by-products after disinfection with chlorine dioxide has been
      determined, and their occurrence in drinking water on board has been examined
      with respect to a possible correlation between water quality and the formation of
      chlorate and chlorite. Therefore, a chromatographic method was developed and
      validated in order to determine the periodical development of chlorate and
      chlorite from chorine dioxide in purified water at different pH-values as well as
      in actual drinking water samples from water conduits on board. The formation of
      the by-products chlorite and chlorate after disinfection with chlorine dioxide is
      influenced neither by pH-value nor by chemical properties of the disinfected
      water. Considering the examined conditions, chlorine dioxide is suitable for
      usage on board due to its simple handling and the low potential of producing by
      products.

PMID- 21900044
TI  - Interpersonal and temporal variability of urinary cotinine in elderly subjects.
AB  - Although a single measurement of urinary cotinine is often used for biological
      monitoring, the validity of this measurement for estimating long-term exposure
      has not been well evaluated. The purpose of this study was to determine the
      efficacy of using a single measurement per person to estimate long-term smoking
      exposure in an elderly population. Analysis was conducted using a cohort of
      elderly subjects for whom multiple urinary cotinine measurements had been
      collected over eight weeks. The mixed-effects model of urinary cotinine indicated
      that interpersonal variability was greater than temporal variability. The
      efficacy of using single measurements to track the mean long-term exposure of a
      population is supported by the relatively consistent population averages. The
      classification of high and low exposure groups using a single measurement or
      using eight measurements produced similar group distributions. When using cut-off
      levels of 20 and 100 MUg cotinine/g creatinine, 9.3% and 5.6% of individual
      exposures were misclassified, respectively, when using a single measurement.
      Urinary cotinine can be a useful biomarker for characterizing exposure to tobacco
      smoke. Although the incidence of misclassification decreased with an increase in
      the number of measurements, a single measurement of the urinary cotinine level
      may accurately represent long-term exposure to tobacco smoke.

PMID- 21900045
TI  - Approach to the difficult transseptal: diathermy facilitated left atrial access.
AB  - Percutaneous transseptal left atrial (LA) access is increasingly becoming a
      routine procedure in the electrophysiology and cardiac catheterisation
      laboratories. Our aim was to review an unselected large series of this procedure
      performed over a period of five years. We clinically characterised difficult
      cases and presented a method of safe and expeditious LA access. Overall, 543
      transseptal punctures were performed. Of those, 10 were classified as difficult,
      with failure to access the LA in three or more attempts. In all 10 cases,
      surgical electrocautery was successfully used to facilitate needle puncture of
      the septum. All patients subsequently underwent an uncomplicated procedure. In
      conclusion, we describe a method to trouble-shoot the difficult transseptal
      access procedure, outlining the clinical characteristics, echocardiographic
      features and special precautions that need to be considered when utilising this
      method.

PMID- 21900046
TI  - Preimplantation factor negates embryo toxicity and promotes embryo development in
      culture.
AB  - Preimplantation factor (PIF) is secreted by viable mammalian embryos and promotes
      implantation and trophoblast invasion. Whether PIF also has a direct protective
      or promoting effect on the developing embryo in culture is unknown. This study
      examined the protective effects of synthetic PIF (sPIF) on embryos cultured with
      embryo toxic serum (ETS) from recurrent pregnancy loss patients (n=14), by
      morphological criteria at 72 h of culture, and determined sPIF-promoting effect
      on singly cultured bovine IVF embryo development. sPIF negated the ETS-induced
      effect by increasing mouse blastocyst rate versus other embryonic stages (odds
      ratio (OR) 2.01, 95% confidence intervals (CI) 1.14-3.55, chi-squared=12.74,
      P=0.002), increased blastocyst rate (39.0% versus 23.7% ETS alone) and lowered
      embryo demise rate (11.0% versus 28.8%, OR 0.24, 95% CI 0.11-0.54), which was not
      replicated by scrambled PIF or the control. sPIF added to bovine embryos for 3
      days promoted development at day 7 of culture (11% versus 0%, chi-squared=4.0,
      P=0.045). In conclusion, sPIF prevented embryo demise caused by exposure to ETS
      and promoted development of singly cultured bovine IVF embryos following short
      term exposure. sPIF-based therapy for reducing recurrent pregnancy loss and
      improving lagging cultured IVF embryo development should be explored.

PMID- 21900047
TI  - Subtractive screening with the Mycobacterium tuberculosis surface protein phage
      display library.
AB  - Surface proteins consist of secreted and membrane proteins and play a central
      role in the interaction of the pathogen with its environment, especially in the
      pathogenicity of Mycobacterium tuberculosis (MTB). Research on surface proteins
      in MTB has focused on 2D electrophoresis of culture filtrate proteins (CFP),
      extraction of transmembrane proteins with detergent and predicting their
      properties with a range of available algorithms. However, functional analysis of
      these secretomes is possible only if many proteins are expressed and purified
      individually, which limits a large number of studies to the function of the
      proteome. Here, we utilized a phage display system to construct a whole genomic
      surface protein phage display library of MTB, which can complete direct
      selection, identification, expression, purification and functional research of
      surface proteins of MTB. With this system we made a new serological approach
      involving iterative subtraction screening. Cross-reactivity of antibodies was
      reduced by preadsorption of the surface protein phage display library with the
      sera of healthy BCG-vaccinated individuals prior to studying their reactivity
      against the sera of tuberculosis (TB) patients. As a result six antigens were
      identified, three of which have not previously been reported as diagnosis
      antigens. The surface protein phage display library shows great promise in the
      study of MTB.

PMID- 21900048
TI  - Transfusion and apheresis science. Editorial.

PMID- 21900049
TI  - Re: Abdeldaim et al., 2011.

PMID- 21900050
TI  - The effect of a recessionary economy on food choice: implications for nutrition
      education.
AB  - OBJECTIVE: To determine the effect of an economic recession on food choice
      behaviors. DESIGN: A qualitative study using semistructured, in-depth interviews
      followed by completion of a nutrition knowledge questionnaire and the Food Choice
      Questionnaire was conducted. SETTING AND PARTICIPANTS: A convenience sample from
      a metropolitan city in the Midwest. Women with children younger than 18 years in
      the household who had experienced unemployment, underemployment, or loss of a
      house because of foreclosure in the previous year participated (n = 25). MAIN
      OUTCOME MEASURE: Reported behaviors for food choices when grocery shopping and
      dining out and educational resources requested to inform nutrition education
      programs. ANALYSIS: Interviews were coded with a matrix derived from participant
      statements. Common behaviors were grouped and broad themes were identified.
      RESULTS: Numerous shopping strategies were recently used to save money (eg,
      buying only sale items, using coupons). Participants believed a healthful diet
      included a variety of foods with less sugar, salt, and fat. Recipes and menus
      that required little cost or preparation time and resources to track food
      expenditures were desired. CONCLUSIONS AND IMPLICATIONS: Nutrition education
      should include money-saving shopping strategies, facilitate menu planning and
      cooking skills, and address food resource management to enable participants to
      acquire sufficient, acceptable, and nutritionally adequate food.

PMID- 21900051
TI  - Healthy children, healthy families: parents making a difference! A curriculum
      integrating key nutrition, physical activity, and parenting practices to help
      prevent childhood obesity.

PMID- 21900052
TI  - Brca2, Rad51 and Mre11: performing balancing acts on replication forks.
AB  - Homologous recombination (HR) is required for faithful repair of double strand
      breaks (DSBs) and is believed to be important for DNA replication under stressful
      conditions in unicellular organisms. However, its role during DNA replication in
      high eukaryotes has always been elusive. In particular, due to the essential
      nature of its main players it has been difficult to dissect the direct role of HR
      in DNA replication. Recent studies revealed that some key HR factors such as
      Rad51 and BRCA2 play unexpected functions during DNA replication by protecting
      nascent DNA from Mre11 mediated degradation, which takes place at stalled
      replication forks. These novel functions appear to be essential to ensure smooth
      progression of DNA replication and to promote maintenance of genome stability.

PMID- 21900053
TI  - Molecularly imprinted microspheres as SPE sorbent for selective extraction of
      four Sudan dyes in catsup products.
AB  - A highly selective molecularly imprinted solid-phase extraction (MISPE) coupled
      with high performance liquid chromatography (HPLC) ultraviolet-visible detection
      was developed for the simultaneous isolation and determination of four Sudan dyes
      (I, II, III and IV) in catsup products. The novel molecularly imprinted
      microspheres (MIM) were synthesized by aqueous suspension polymerization using
      phenylamine and naphthol as template, which showed high affinity to Sudan dyes in
      aqueous solution. In order to develop a selective extraction protocol for
      simultaneous determination the four Sudan dyes from catsup products, the
      molecular recognition properties of MIM as a SPE sorbent were evaluated. Under
      the optimized condition, good linearity was obtained from 0.01 to 2.5 MUg g(-1)
      (r(2)>= 0.9990) with the relative standard deviations of less than 3.4%. This
      proposed MISPE-HPLC procedure eliminated the effect of template leakage on
      quantitative analysis and could be applied to direct determination of four Sudan
      dyes in complicated food samples.

PMID- 21900054
TI  - Detection and identification of a serine to arginine sequence variant in a
      therapeutic monoclonal antibody.
AB  - Sequence variants, also known as unintended amino acid substitutions in the
      protein primary structure, are one of the critical quality attributes needed to
      be monitored during process development of monoclonal antibodies (mAbs). Here we
      report on analytical methods for detection and identification of a sequence
      variant in an IgG1 mAb expressed in Chinese hamster ovary (CHO) cells. The
      presence of the sequence variant was detected by an imaged capillary isoelectric
      focusing (ICIEF) assay, showing a new basic species in mAb charge variant
      profile. The new basic variant was fractionated and enriched by ion-exchange
      chromatography, analyzed by reduced light and heavy chain mass determination, and
      characterized by HPLC-UV/MS/MS of tryptic and endoproteinase Lys-C peptide maps.
      A Serine to Arginine sequence variant was identified at the heavy chain 441
      position (S441R), and confirmed by using synthetic peptides. The relative level
      of the S441R variant was estimated to be in the range of 0.3-0.6% for several mAb
      batches analyzed via extracted ion chromatogram (EIC). This work demonstrates the
      effectiveness of using integrated analytical methods to detect and identify
      protein heterogeneity and the importance of monitoring product quality during mAb
      bioprocess development.

PMID- 21900055
TI  - Assessing molecular chirality with twisted light: comment on "Photochirogenesis:
      photochemical models on the absolute asymmetric formation of amino acids in
      interstellar space" by Uwe J. Meierhenrich et al.

PMID- 21900056
TI  - Davydov-Pang model: an improved Davydov protein soliton theory: comment on "The
      theory of bio-energy transport in the protein molecules and its properties" by
      Xiaofeng Pang.

PMID- 21900058
TI  - Is faecal-immunochemical test useful in patients with iron deficiency anaemia and
      without overt bleeding?
AB  - BACKGROUND: Both upper and lower endoscopies are indicated in patients with iron
      deficiency anaemia. However, these examinations are negative in a high proportion
      of cases. AIMS: To assess whether faecal-immunochemical test (FIT) may be useful
      in selecting patients at higher risk of bleeding lesions in iron deficiency
      anaemia patients. METHODS: Iron deficiency anaemia patients without overt
      bleeding were prospectively enrolled. All patients performed FIT, and underwent
      both upper and lower endoscopy. Predictive factors of potential bleeding lesions
      were evaluated at multivariate analysis. RESULTS: FIT was positive in 48 (34.3%)
      out of 140 enrolled patients, and a potential bleeding lesion was present in 63
      (45%) patients. An endoscopic lesion was detected more frequently in FIT-positive
      than -negative patients (79.2% vs 27.2%; p<0.0001), at both upper endoscopy
      (52.1% vs 18.5%; p=0.0002) and colonoscopy (33.3% vs 8.7%; p=0.001). At
      multivariate analysis, FIT was found to be an independent predictor of both
      bleeding lesions (OR=9.5; 95% CI: 4.1-22; p<0.001) and cancer (OR=4.0, CI: 1.1
      15; p=0.029). CONCLUSIONS: FIT positive-iron deficiency anaemia patients without
      overt bleeding are at increased risk to present with a bleeding lesion at
      endoscopy, including cancer. FIT positivity in this setting could be useful to
      prioritize urgent endoscopy.

PMID- 21900057
TI  - Identification of MLL partner genes in 27 patients with acute leukemia from a
      single cytogenetic laboratory.
AB  - Chromosomal rearrangements involving the MLL gene have been associated with many
      different types of hematological malignancies. Fluorescent in situ hybridization
      with a panel of probes coupled with long distance inverse-PCR was used to
      identify chromosomal rearrangements involving the MLL gene. Between 1995 and
      2010, 27 patients with an acute leukemia were found to have a fusion gene
      involving MLL. All seven ALL patients with B cell acute lymphoblastic leukemia
      were characterized by the MLL/AFF1 fusion gene resulting from a translocation (5
      patients) or an insertion (2 patients). In the 19 AML patients with acute
      myeloblastic leukemia, 31.6% of all characterized MLL fusion genes were
      MLL/MLLT3, 21.1% MLL/ELL, 10.5% MLL/MLLT6 and 10.5% MLL/EPS15. Two patients had
      rare or undescribed fusion genes, MLL/KIAA0284 and MLL/FLNA. Seven patients (26%)
      had a complex chromosomal rearrangement (three-way translocations, insertions,
      deletions) involving the MLL gene. Splicing fusion genes were found in three
      patients, leading to a MLL/EPS15 fusion in two and a MLL/ELL fusion in a third
      patient. This study showed that fusion involving the MLL gene can be generated
      through various chromosomal rearrangements such as translocations, insertions and
      deletions, some being complex or cryptic. A systematic approach should be used in
      all cases of acute leukemia starting with FISH analyses using a commercially
      available MLL split signal probe. Then, the analysis has to be completed, if
      necessary, by further molecular cytogenetic and genomic PCR methods.

PMID- 21900059
TI  - [Late-presenting congenital diaphragmatic hernia].

PMID- 21900060
TI  - [Potential maleficence of predictive medicine].

PMID- 21900061
TI  - Pure skin perforator flap for microtia and congenital aural atresia using
      supermicrosurgical techniques.
AB  - Microtia or pinna deformities with congenital aural atresia are severe conditions
      that significantly affect the quality of life. Although several surgical
      treatments have been proposed for aural atresia, revision surgery is often
      required to address complications associated with the initial procedure, which
      include external auditory canal stenosis, lateralization of the tympanic membrane
      and chronic recurrent otorrhea. However, such problems may be addressed by using
      vascularized skin. We herein report a new method of reconstruction for congenital
      aural atresia in three cases using the superficial circumflex iliac artery as a
      pure skin perforator flap. MATERIALS & METHODS: The branch of the superficial
      circumflex iliac artery perforator was traced distally to a point where it
      penetrated the dermis. After identifying the branch of the perforator penetrating
      the dermis (termed the "pure skin perforator"), the pure skin perforator flap was
      elevated. A new external auditory canal was then created by drilling through the
      mastoid air cells and atresia plate. The pure skin perforator flap was folded
      into a 1.5*3 cm sac, which was placed into the external auditory canal. The
      superficial circumflex iliac artery and the superficial circumflex iliac vein
      were anastomosed to the superficial temporal artery and the superficial temporal
      vein, respectively. RESULTS: All of the pure skin perforator flaps survived. The
      flap sizes varied from 10*2.5 to 10*4 cm (average area of 32.5 cm2). These skin
      perforator flaps were all 2 mm thick. CONCLUSION: Pure skin perforator flaps fed
      only by the dermal subpapillary plexus survived, regardless of the presence of
      the subdermal plexus. The pure skin perforator flap can be as thin as a skin
      graft and it has the possibility to reduce the complications that frequently
      occur when the previously reported procedures are used.

PMID- 21900062
TI  - "Bouncing back": how Australia's leading women's magazines portray the postpartum
      'body'.
AB  - PURPOSE: To examine how the Australian media portrays the childbearing body
      through the use of celebrity stories in women's magazines. The study aimed to
      provide insight into socially constructed factors that might influence women's
      body image and expectations during pregnancy and the early postnatal period.
      METHOD: Media content analysis was used to analyse 25 celebrity stories about the
      childbearing postnatal body (images and texts) collected from Australia's three
      leading women's magazines between January and June 2009 (n=58). FINDINGS: A
      variety of persuasive textual and visual messages were elicited. The major theme
      representing how the postnatal body was constructed was labelled 'Bouncing back';
      the focus of this paper. The social messages inherent in the magazine stories
      were that women need to strive towards regaining a pre-pregnant body shape with
      the same effort one would employ when recovering from an illness. Three specific
      sub-themes that promoted weight loss were identified. These were labelled 'Racing
      to bounce back', 'Breastfeeding to bounce back' and 'Pretending to bounce back'.
      A fourth sub-theme, 'Refusing to bounce back: Celebrating my new body', grouped
      together stories about celebrities who appeared to embrace their changed, but
      healthy, postnatal body. CONCLUSIONS: The study highlighted the expectations of
      the postpartum body in relation to speedy return to the pre-pregnant state.
      Understanding how these portrayals may contribute to women's own body image and
      expectations in the early postpartum period may better assist maternity health
      care providers to engage with women in meaningful discussions about this
      important time in their lives and challenge notions of ideal body types.
      Assisting women to accept and nurture themselves and have confidence in their
      ability as a new parent is a crucial element of quality maternity service
      provision.

PMID- 21900063
TI  - Reviewing and reflecting on practice: the midwives experiences of credentialling.
AB  - RESEARCH QUESTION: What are the experiences of midwives working in midwifery-led
      models of care in NSW who undertake the credentialling process? BACKGROUND: In
      2005, the NSW Health Department issued a directive requiring midwives who worked
      in midwifery-led models of care to undergo a process known as credentialling.
      Credentialling involved a four-step process: self-assessment, face-to-face panel
      review of midwifery practice, assessment of emergency management skills and
      discussion of a case study from practice. METHOD: A descriptive exploratory study
      examined the experiences of the midwives who undertook the credentialling process
      in NSW. Data were collected through in-depth, semi-structured interviews with 12
      midwives who had experienced credentialling and analysed using descriptive and
      thematic analysis. FINDINGS: The themes were preparing for credentialling; doing
      credentialling; achieving credentialling; valuing credentialling; and, improving
      credentialling. Initially, the midwives were self-focused in their understanding
      and impressions of the value of credentialling. There were a number of
      contentions including seeing credentialling as another 'hoop to jump through' or
      a need to 'tick the box' and not as a framework for practice. Some viewed it as a
      necessary move to increase professionalism and facilitate practice review. Others
      felt they were being unfairly targeted as not all midwives were expected to
      undertake it. The midwives were cognisant of the need for a process that
      encouraged responsibility for ongoing professional development and continuing
      competence and believed the process would be useful in promoting deeper
      reflection on practice. IMPLICATIONS FOR PRACTICE: Credentialling was recognised
      as being valuable for all midwives to undertake as it encourages both a review
      of, and reflection on, practice. The process has further developed into Midwifery
      Practice Review (MPR) and is administered by the national professional
      association for midwifery.

PMID- 21900064
TI  - Women's knowledge of options for birth after Caesarean Section.
AB  - OBJECTIVE: In Australia, the Caesarean Section rate has risen from 21.8% to 31.1%
      (2010) in a decade; in South Australia the rate was 32.2% in 2009. Caesarean
      Section is a life saving intervention in certain circumstances, but also a major
      surgical procedure with potential adverse effects on both mother and baby. The
      aim of this study was to ascertain the determinants of knowledge regarding
      options for subsequent birth in women who have experienced a previous Caesarean
      Section with a live baby. METHOD: A sample of 33 women in South Australia who had
      a previous Caesarean Section were surveyed to assess their awareness of birth
      options and their advantages versus disadvantages as well as the possible factors
      influencing their information gathering and decision-making on birth options for
      their subsequent pregnancy. FINDINGS: Most women perceived Caesarean Section to
      be major surgery but 69.6% were not aware that babies might have problems with
      breastfeeding, 60.6% did not know the rarity of uterine rupture during labour
      and/or birth and 48.5% were not aware that a caesarean may involve any
      complications for the baby at or after birth. CONCLUSION: Women's knowledge
      deficits relating to risks and benefits of birth options after previous caesarean
      can constrain them as most women chose caesarean rather than normal birth in
      their subsequent pregnancy.

PMID- 21900065
TI  - Analysis of matches and partial-matches in a Danish STR data set.
AB  - Over the recent years, the national databases of STR profiles have grown in size
      due to the success of forensic DNA analysis in solving crimes. The accumulation
      of DNA profiles implies that the probability of a random match or near match of
      two randomly selected DNA profiles in the database increases. We analysed 53,295
      STR profiles from individuals investigated in relation to crime case
      investigations at the Department of Forensic Medicine, Faculty of Health
      Sciences, University of Copenhagen, Denmark. Incomplete STR profiles (437 circa
      0.8% of the total), 48 redundant STR profiles from monozygotic twins (0.09%), 6
      redundant STR profiles of unknown cause and 1283 STR profiles from repeated
      testing of individuals were removed leaving 51,517 complete 10 locus STR profiles
      for analysis. The number corresponds to approximately 1% of the Danish
      population. We compared all STR profiles to each other, i.e. 1.3*10(9)
      comparisons. With these large number of comparisons, it is likely to observe DNA
      profiles that coincide on many loci, which has concerned some commentators and
      raised questions about "overstating" the power of DNA evidence. We used the
      method of Weir [11,12] and Curran et al. [3] to compare the observed and expected
      number of matches and near matches in the data set. We extended the methods by
      computing the covariance matrix of the summary statistic and used it for the
      estimation of the identical-by-descent parameter, theta. The analysis
      demonstrated a number of close relatives in the Danish data set and substructure.
      The main contribution to the substructure comes from close relatives. An overall
      theta-value of 1% compensated for the observed substructure, when close familial
      relationships were accounted for.

PMID- 21900066
TI  - Pediatricians' attitudes about collaborations with other community vaccinators in
      the delivery of seasonal influenza vaccine.
AB  - OBJECTIVE: Achieving universal influenza vaccination among children may
      necessitate collaborative delivery involving both practices and community
      vaccinators. We assessed among pediatricians nationally their preferences
      regarding location of influenza vaccination for patient subgroups and their
      attitudes about collaborative delivery methods. METHODS: The design/setting was a
      national survey conducted from July 2009 to October 2009. Participants included a
      representative sample of pediatricians from the American Academy of Pediatrics.
      RESULTS: The response rate was 79% (330 of 416). Physicians felt strongly that
      vaccination should occur in their practice for children with chronic conditions
      (52%) and healthy 6-24-month-old infants (48%), but few felt strongly about
      healthy 5-18-year-olds (17%). Most (78%) thought having multiple delivery sites
      increased vaccination rates, and 86% thought that influenza vaccine should be
      available at school. Physicians reported being very/somewhat willing to hold
      joint community clinics with public health entities (76%) and to suggest to
      patient subgroups that they receive vaccine at community sites, including public
      clinics or pharmacies (76%). The most frequently reported barriers to
      collaborative delivery with community sites or school-located delivery included
      concerns about the following: estimating the amount of vaccine to order if
      children are vaccinated elsewhere (community 56%; school 80%); transfer of
      vaccine records (community 57%; school 78%); and reluctance of families to go
      outside of the office (community 45%; school 74%). CONCLUSIONS: Most physicians
      are in favor of school-located or collaborative influenza vaccine delivery with
      community vaccinators, especially for healthy school-aged children. Collaborative
      approaches will require planning to ensure transfer of records, effective
      targeting of subgroups, and provisions to protect providers from being left with
      extra influenza supply.

PMID- 21900067
TI  - Equivalent pulse parameters for electroporation.
AB  - Electroporation-based applications require the use of specific pulse parameters
      for a successful outcome. When recommended values of pulse parameters cannot be
      set, similar outcomes can be obtained by using equivalent pulse parameters. We
      determined the relations between the amplitude and duration/number of pulses
      resulting in the same fraction of electroporated cells. Pulse duration was varied
      from 150 ns to 100 ms, and the number of pulses from 1 to 128. Fura 2-AM was used
      to determine electroporation of cells to Ca(2+). With longer pulses or higher
      number of pulses, lower amplitudes are needed for the same fraction of
      electroporated cells. The expression derived from the model of electroporation
      could describe the measured data on the whole interval of pulse durations. In a
      narrower range (0.1-100 ms), less complex, logarithmic or power functions could
      be used instead. The relation between amplitude and number of pulses could best
      be described with a power function or an exponential function. We show that
      relatively simple two-parameter power or logarithmic functions are useful when
      equivalent pulse parameters for electroporation are sought. Such mathematical
      relations between pulse parameters can be important in planning of
      electroporation-based treatments, such as electrochemotherapy and nonthermal
      irreversible electroporation.

PMID- 21900068
TI  - Automatic identification of functional clusters in FMRI data using spatial
      dependence.
AB  - In independent component analysis (ICA) of functional magnetic resonance imaging
      (fMRI) data, extracting a large number of maximally independent components
      provides a detailed functional segmentation of brain. However, such high-order
      segmentation does not establish the relationships among different brain networks,
      and also studying and classifying components can be challenging. In this study,
      we present a multidimensional ICA (MICA) scheme to achieve automatic component
      clustering. In our MICA framework, stable components are hierarchically grouped
      into clusters based on higher order statistical dependence--mutual information-
      among spatial components, instead of the typically used temporal correlation
      among time courses. The final cluster membership is determined using a
      statistical hypothesis testing method. Since ICA decomposition takes into account
      the modulation of the spatial maps, i.e., temporal information, our ICA-based
      approach incorporates both spatial and temporal information effectively. Our
      experimental results from both simulated and real fMRI datasets show that the use
      of spatial dependence leads to physiologically meaningful connectivity structure
      of brain networks, which is consistently identified across various ICA model
      orders and algorithms. In addition, we observe that components related to
      artifacts, including cerebrospinal fluid, arteries, and large draining veins, are
      grouped together and encouragingly distinguished from other components of
      interest.

PMID- 21900069
TI  - Vesicoureteral reflux in children: a phantom study of microwave heating and
      radiometric thermometry of pediatric bladder.
AB  - We have investigated the use of microwave heating and radiometry to safely heat
      urine inside a pediatric bladder. The medical application for this research is to
      create a safe and reliable method to detect vesicoureteral reflux, a pediatric
      disorder, where urine flow is reversed and flows from the bladder back up into
      the kidney. Using fat and muscle tissue models, we have performed both
      experimental and numerical simulations of a pediatric bladder model using planar
      dual concentric conductor microstrip antennas at 915 MHz for microwave heating. A
      planar elliptical antenna connected to a 500 MHz bandwidth microwave radiometer
      centered at 3.5 GHz was used for noninvasive temperature measurement inside
      tissue. Temperatures were measured in the phantom models at points during the
      experiment with implanted fiberoptic sensors, and 2-D distributions in cut planes
      at depth in the phantom with an infrared camera at the end of the experiment.
      Cycling between 20 s with 20 Watts power for heating, and 10 s without power to
      allow for undisturbed microwave radiometry measurements, the experimental results
      show that the target tissue temperature inside the phantom increases fast and
      that the radiometer provides useful measurements of spatially averaged
      temperature of the illuminated volume. The presented numerical and experimental
      results show excellent concordance, which confirms that the proposed system for
      microwave heating and radiometry is applicable for safe and reliable heating of
      pediatric bladder.

PMID- 21900070
TI  - Murine cardiac catheterizations and hemodynamics: on the issue of parallel
      conductance.
AB  - Catheter-based measurements are extensively used nowadays in animal models to
      quantify global left ventricular (LV) cardiac function and hemodynamics.
      Conductance catheter measurements yield estimates of LV volumes. Such estimates,
      however, are confounded by the catheter's nonhomogeneous emission field and the
      contribution to the total conductance of surrounding tissue or blood conductance
      values (other than LV blood), a term often known as parallel conductance. In
      practice, in most studies, volume estimates are based on the assumptions that the
      catheter's electric field is homogeneous and that parallel conductance is
      constant, despite prior results showing that these assumptions are incorrect.
      This study challenges the assumption for spatial homogeneity of electric field
      excitation of miniature catheters and investigated the electric field
      distribution of miniature catheters in the murine heart, based on cardiac model
      driven (geometric, lump component) simulations and noninvasive imaging, at both
      systolic and diastolic cardiac phases. Results confirm the nonuniform catheter
      emission field, confined spatially within the LV cavity and myocardium, falling
      to 10% of its peak value at the ring electrode surface, within 1.1-2.0 mm, given
      a relative tissue permittivity of 33,615. Additionally, <1% of power leaks were
      observed into surrounding cavities or organs at end-diastole. Temporally varying
      parallel conductance effects are also confirmed, becoming more prominent at end
      systole.

PMID- 21900071
TI  - HRF estimation in fMRI data with an unknown drift matrix by iterative
      minimization of the Kullback-Leibler divergence.
AB  - Hemodynamic response function (HRF) estimation in noisy functional magnetic
      resonance imaging (fMRI) plays an important role when investigating the temporal
      dynamic of a brain region response during activations. Nonparametric methods
      which allow more flexibility in the estimation by inferring the HRF at each time
      sample have provided improved performance in comparison to the parametric
      methods. In this paper, the mixed-effects model is used to derive a new algorithm
      for nonparametric maximum likelihood HRF estimation. In this model, the random
      effect is used to better account for the variability of the drift. Contrary to
      the usual approaches, the proposed algorithm has the benefit of considering an
      unknown and therefore flexible drift matrix. This allows the effective
      representation of a broader class of drift signals and therefore the reduction of
      the error in approximating the drift component. Estimates of the HRF and the
      hyperparameters are derived by iterative minimization of the Kullback-Leibler
      divergence between a model family of probability distributions defined using the
      mixed-effects model and a desired family of probability distributions constrained
      to be concentrated on the observed data. The performance of proposed method is
      demonstrated on simulated and real fMRI data, the latter originating from both
      event-related and block design fMRI experiments.

PMID- 21900072
TI  - Delay-independent stability of genetic regulatory networks.
AB  - Genetic regulatory networks can be described by nonlinear differential equations
      with time delays. In this paper, we study both locally and globally delay
      independent stability of genetic regulatory networks, taking messenger
      ribonucleic acid alternative splicing into consideration. Based on nonnegative
      matrix theory, we first develop necessary and sufficient conditions for locally
      delay-independent stability of genetic regulatory networks with multiple time
      delays. Compared to the previous results, these conditions are easy to verify.
      Then we develop sufficient conditions for global delay-independent stability for
      genetic regulatory networks. Compared to the previous results, this sufficient
      condition is less conservative. To illustrate theorems developed in this paper,
      we analyze delay-independent stability of two genetic regulatory networks: a real
      life repressilatory network with three genes and three proteins, and a synthetic
      gene regulatory network with five genes and seven proteins. The simulation
      results show that the theorems developed in this paper can effectively determine
      the delay-independent stability of genetic regulatory networks.

PMID- 21900073
TI  - Efficient revised simplex method for SVM training.
AB  - Existing active set methods reported in the literature for support vector machine
      (SVM) training must contend with singularities when solving for the search
      direction. When a singularity is encountered, an infinite descent direction can
      be carefully chosen that avoids cycling and allows the algorithm to converge.
      However, the algorithm implementation is likely to be more complex and less
      computationally efficient than would otherwise be required for an algorithm that
      does not have to contend with the singularities. We show that the revised simplex
      method introduced by Rusin provides a guarantee of nonsingularity when solving
      for the search direction. This method provides for a simpler and more
      computationally efficient implementation, as it avoids the need to test for rank
      degeneracies and also the need to modify factorizations or solution methods based
      upon those rank degeneracies. In our approach, we take advantage of the guarantee
      of nonsingularity by implementing an efficient method for solving the search
      direction and show that our algorithm is competitive with SVM-QP and also that it
      is a particularly effective when the fraction of nonbound support vectors is
      large. In addition, we show competitive performance of the proposed algorithm
      against two popular SVM training algorithms, SVMLight and LIBSVM.

PMID- 21900074
TI  - Multistability of second-order competitive neural networks with nondecreasing
      saturated activation functions.
AB  - In this paper, second-order interactions are introduced into competitive neural
      networks (NNs) and the multistability is discussed for second-order competitive
      NNs (SOCNNs) with nondecreasing saturated activation functions. Firstly, based on
      decomposition of state space, Cauchy convergence principle, and inequality
      technique, some sufficient conditions ensuring the local exponential stability of
      2N equilibrium points are derived. Secondly, some conditions are obtained for
      ascertaining equilibrium points to be locally exponentially stable and to be
      located in any designated region. Thirdly, the theory is extended to more general
      saturated activation functions with 2r corner points and a sufficient criterion
      is given under which the SOCNNs can have (r+1)N locally exponentially stable
      equilibrium points. Even if there is no second-order interactions, the obtained
      results are less restrictive than those in some recent works. Finally, three
      examples with their simulations are presented to verify the theoretical analysis.

PMID- 21900075
TI  - Embedding prior knowledge within compressed sensing by neural networks.
AB  - In the compressed sensing framework, different algorithms have been proposed for
      sparse signal recovery from an incomplete set of linear measurements. The most
      known can be classified into two categories:  l(1) norm minimization-based
      algorithms and  l(0) pseudo-norm minimization with greedy matching pursuit
      algorithms. In this paper, we propose a modified matching pursuit algorithm based
      on the orthogonal matching pursuit (OMP). The idea is to replace the correlation
      step of the OMP, with a neural network. Simulation results show that in the case
      of random sparse signal reconstruction, the proposed method performs as well as
      the OMP. Complexity overhead, for training and then integrating the network in
      the sparse signal recovery is thus not justified in this case. However, if the
      signal has an added structure, it is learned and incorporated in the proposed new
      OMP. We consider three structures: first, the sparse signal is positive, second
      the positions of the non zero coefficients of the sparse signal follow a certain
      spatial probability density function, the third case is a combination of both.
      Simulation results show that, for these signals of interest, the probability of
      exact recovery with our modified OMP increases significantly. Comparisons with 
      l(1) based reconstructions are also performed. We thus present a framework to
      reconstruct sparse signals with added structure by embedding, through neural
      network training, additional knowledge to the decoding process in order to have
      better performance in the recovery of sparse signals of interest.

PMID- 21900076
TI  - Stabilization of nonlinear systems using sampled-data output-feedback fuzzy
      controller based on polynomial-fuzzy-model-based control approach.
AB  - This paper investigates the stability of sampled-data output-feedback (SDOF)
      polynomial-fuzzy-model-based control systems. Representing the nonlinear plant
      using a polynomial fuzzy model, an SDOF fuzzy controller is proposed to perform
      the control process using the system output information. As only the system
      output is available for feedback compensation, it is more challenging for the
      controller design and system analysis compared to the full-state-feedback case.
      Furthermore, because of the sampling activity, the control signal is kept
      constant by the zero-order hold during the sampling period, which complicates the
      system dynamics and makes the stability analysis more difficult. In this paper,
      two cases of SDOF fuzzy controllers, which either share the same number of fuzzy
      rules or not, are considered. The system stability is investigated based on the
      Lyapunov stability theory using the sum-of-squares (SOS) approach. SOS-based
      stability conditions are obtained to guarantee the system stability and
      synthesize the SDOF fuzzy controller. Simulation examples are given to
      demonstrate the merits of the proposed SDOF fuzzy control approach.

PMID- 21900077
TI  - Exposure to phthalates and phenols during pregnancy and offspring size at birth.
AB  - BACKGROUND: Data concerning the effects of prenatal exposures to phthalates and
      phenols on fetal growth are limited in humans. Previous findings suggest possible
      effects of some phenols on male birth weight. OBJECTIVE: Our aim was to assess
      the relationships between prenatal exposures to phthalates and phenols and fetal
      growth among male newborns. METHODS: We conducted a case-control study on male
      malformations of the genitalia nested in two French mother-child cohorts with
      recruitment between 2002 and 2006. We measured, in maternal urinary samples
      collected between 6 and 30 gestational weeks, the concentrations (micrograms per
      liter) of 9 phenol (n = 191 pregnant women) and 11 phthalate metabolites (n =
      287). Weight, length, and head circumference at birth were collected from
      maternity records. Statistical analyses were corrected for the oversampling of
      malformation cases. RESULTS: Adjusted birth weight decreased by 77 g [95%
      confidence interval (CI): -129, -25] and by 49 g (95% CI: -86, -13) in
      association with a 1-unit increase in ln-transformed 2,4-dichlorophenol (DCP) and
      2,5-DCP urinary concentrations, respectively. Benzophenone-3 (BP3) ln-transformed
      concentrations were positively associated with weight (26 g; 95% CI: -2, 54) and
      head circumference at birth (0.1 cm; 95% CI: 0.0, 0.2). Head circumference
      increased by 0.3 cm (95% CI: 0.0, 0.7) in association with a 1-unit increase in
      ln-transformed BPA concentration. For phthalate metabolites there was no evidence
      of monotonic associations with birth weight. CONCLUSIONS: Consistent with
      findings of a previous study, we observed evidence of an inverse association of
      2,5-DCP and a positive association of BP3 with male birth weight.

PMID- 21900078
TI  - The impact of regional climate change on malaria risk due to greenhouse forcing
      and land-use changes in tropical Africa.
AB  - BACKGROUND: Climate change will probably alter the spread and transmission
      intensity of malaria in Africa. OBJECTIVES: In this study, we assessed potential
      changes in the malaria transmission via an integrated weather-disease model.
      METHODS: We simulated mosquito biting rates using the Liverpool Malaria Model
      (LMM). The input data for the LMM were bias-corrected temperature and
      precipitation data from the regional model (REMO) on a 0.5 degrees  latitude
      longitude grid. A Plasmodium falciparum infection model expands the LMM
      simulations to incorporate information on the infection rate among children.
      Malaria projections were carried out with this integrated weather-disease model
      for 2001 to 2050 according to two climate scenarios that include the effect of
      anthropogenic land-use and land-cover changes on climate. RESULTS: Model-based
      estimates for the present climate (1960 to 2000) are consistent with observed
      data for the spread of malaria in Africa. In the model domain, the regions where
      malaria is epidemic are located in the Sahel as well as in various highland
      territories. A decreased spread of malaria over most parts of tropical Africa is
      projected because of simulated increased surface temperatures and a significant
      reduction in annual rainfall. However, the likelihood of malaria epidemics is
      projected to increase in the southern part of the Sahel. In most of East Africa,
      the intensity of malaria transmission is expected to increase. Projections
      indicate that highland areas that were formerly unsuitable for malaria will
      become epidemic, whereas in the lower-altitude regions of the East African
      highlands, epidemic risk will decrease. CONCLUSIONS: We project that climate
      changes driven by greenhouse-gas and land-use changes will significantly affect
      the spread of malaria in tropical Africa well before 2050. The geographic
      distribution of areas where malaria is epidemic might have to be significantly
      altered in the coming decades.

PMID- 21900079
TI  - Predicting the restenosis benefit of drug-eluting versus bare metal stents in
      percutaneous coronary intervention.
AB  - BACKGROUND: Drug-eluting stents (DES) for percutaneous coronary intervention
      decrease the risk of restenosis compared with bare metal stents. However, they
      are costlier, require prolonged dual antiplatelet therapy, and provide the most
      benefit in patients at highest risk for restenosis. To assist physicians in
      targeting DES use in patients at the highest risk for target vessel
      revascularization (TVR), we developed and validated a model to predict TVR.
      METHODS AND RESULTS: Preprocedural clinical and angiographic data from 27 107
      percutaneous coronary intervention hospitalizations between October 1, 2004, and
      September 30, 2007, in Massachusetts were used to develop prediction models for
      TVR at 1 year. Models were developed from a two-thirds random sample and
      validated in the remaining third. The overall rate of TVR was 7.6% (6.7% with
      DES, 11% with bare metal stents). Significant predictors of TVR included prior
      percutaneous coronary intervention, emergency or salvage percutaneous coronary
      intervention, prior coronary bypass surgery, peripheral vascular disease,
      diabetes mellitus, and angiographic characteristics. The model was superior to a
      3-variable model of diabetes mellitus, stent diameter, and stent length (c
      statistic, 0.66 versus 0.60; P<0.001) and was well calibrated. The predicted
      number needed to treat with DES to prevent 1 TVR compared with bare metal stents
      ranged from 6 (95% confidence interval, 5.4-7.6) to 80 (95% confidence interval,
      62.7-116.3), depending on patients' clinical and angiographic factors.
      CONCLUSIONS: A predictive model using commonly collected variables can identify
      patients who may derive the greatest benefit in TVR reduction from DES. Whether
      use of the model improves the safety and cost-effectiveness of DES use should be
      tested prospectively.

PMID- 21900082
TI  - Second internal thoracic artery versus radial artery in coronary artery bypass
      grafting: a long-term, propensity score-matched follow-up study.
AB  - BACKGROUND: The best second arterial conduit for multiple arterial
      revascularization (MAR) is still a matter of debate. Previous studies on the
      benefit of either using the radial artery (RA) or the right internal thoracic
      artery (RITA) in coronary artery bypass grafting are not conclusive. The aim of
      our study was to compare the perioperative and long-term outcome of either RA or
      RITA grafts as second conduits for MAR. METHODS AND RESULTS: A consecutive series
      of 1001 patients undergoing first nonemergent coronary artery bypass grafting
      receiving either RA or RITA as second graft for MAR between 2001 and 2010 were
      studied. There were 277 patients receiving a RITA and 724 patients receiving a RA
      in addition to a left internal thoracic artery (LITA). Concomitant saphenous vein
      grafts (SVG) were grafted in addition as necessary. Propensity score-matched
      analysis was performed to compare the 2 groups, bilateral ITA+/-SVG (BITA+/-SVG
      group) and the LITA+RA+/-SVG group relative to overall survival and major adverse
      cardiac and cerebrovascular events-free survival. Hazard ratios and their 95%
      confidence intervals were estimated by COX regression stratified on matched
      pairs. The incidence of perioperative major adverse cardiac and cerebrovascular
      events was significantly lower in the BITA+/-SVG group (1.4% versus 7.6%,
      P<0.001). Overall survival (hazard ratio 0.23; 95% confidence interval 0.066
      0.81; P=0.022) and major adverse cardiac and cerebrovascular events-free survival
      (hazard ratio 0.18; 95% confidence interval 0.08-0.42; P<0.001) were
      significantly better in the BITA+/-SVG group compared to the LITA+RA+/-SVG group.
      CONCLUSIONS: The results of our study provide strong evidence for the superiority
      of a RITA graft compared to RA as a second conduit in MAR.

PMID- 21900081
TI  - Placental growth factor regulates cardiac inflammation through the tissue
      inhibitor of metalloproteinases-3/tumor necrosis factor-alpha-converting enzyme
      axis: crucial role for adaptive cardiac remodeling during cardiac pressure
      overload.
AB  - BACKGROUND: Heart failure is one of the leading causes of mortality and is
      primarily the final stage of several overload cardiomyopathies, preceded by an
      early adaptive hypertrophic response and characterized by coordinated
      cardiomyocyte growth, angiogenesis, and inflammation. Therefore, growth factors
      and cytokines have to be critically regulated during cardiac response to
      transverse aortic constriction. Interestingly, the dual properties of placental
      growth factor as an angiogenic factor and cytokine make it a candidate to
      participate in cardiac remodeling in response to hemodynamic overload. METHODS
      AND RESULTS: After transverse aortic constriction, placental growth factor
      knockout mice displayed a dysregulation of cardiac remodeling, negatively
      affecting muscle growth. Molecular insights underscored that this effect was
      ascribable mainly to a failure in the establishment of adequate inflammatory
      response owing to an impaired activity of tumor necrosis factor-alpha-converting
      enzyme. Interestingly, after transverse aortic constriction, placental growth
      factor knockout mice had strongly increased levels of tissue inhibitor of
      metalloproteinases-3, the main natural TACE inhibitor, thus indicating an
      unbalance of the tissue inhibitor of metalloproteinases-3/tumor necrosis factor
      alpha-converting enzyme axis. Strikingly, when we used an in vivo RNA
      interference approach to reduce tissue inhibitor of metalloproteinases-3 levels
      in placental growth factor knockout mice during transverse aortic constriction,
      we obtained a complete phenotype rescue of early dilated cardiomyopathy.
      CONCLUSIONS: Our results demonstrate that placental growth factor finely tunes a
      balanced regulation of the tissue inhibitor of metalloproteinases-3/tumor
      necrosis factor-alpha-converting enzyme axis and the consequent TNF-alpha
      activation in response to transverse aortic constriction, thus allowing the
      establishment of an inflammatory response necessary for adaptive cardiac
      remodeling.

PMID- 21900080
TI  - Echocardiographic markers of elevated pulmonary pressure and left ventricular
      diastolic dysfunction are associated with exercise intolerance in adults and
      adolescents with homozygous sickle cell anemia in the United States and United
      Kingdom.
AB  - BACKGROUND: Noninvasively assessed pulmonary pressure elevations and left
      ventricular (LV) diastolic dysfunction are associated with increased mortality in
      adults with sickle cell disease, but their relationship to exercise intolerance
      has not been evaluated prospectively. METHODS AND RESULTS: Echocardiography, 6
      minute walk distance, hemolytic rate, and serum concentrations of ferritin and
      erythropoietin were evaluated in a cohort of 483 subjects with homozygous
      hemoglobin S in the U.S. and U.K. Walk-Treatment of Pulmonary Hypertension and
      Sickle Cell Disease with Sildenafil Therapy (Walk-PHaSST) study. Tricuspid
      regurgitation velocity, which reflects systolic pulmonary artery pressure, was
      2.7 to <3.0 m/s (mean+/-SD, 2.8+/-0.1) in 26% of the subjects and >=3.0 m/s
      (mean+/-SD, 3.4+/-0.4) in 11%. The LV lateral E/e' ratio, which has been shown to
      reflect LV filling pressure in other conditions but has not been studied in
      sickle cell disease, was significantly higher in the groups with tricuspid
      regurgitation velocity >=2.7 m/s. Increased hemolysis (P<0.0001), LV lateral E/e'
      ratio (P=0.0001), blood urea nitrogen (P=0.0002), and erythropoietin (P=0.002)
      were independently associated with an increased tricuspid regurgitation velocity.
      Furthermore, female sex (P<0.0001), older age (P<0.0001), LV lateral E/e' ratio
      (P=0.014), and tricuspid regurgitation velocity (P=0.019) were independent
      predictors of a shorter 6-minute walk distance. CONCLUSIONS: Echocardiography
      estimated elevated pulmonary artery systolic pressure and LV lateral E/e' ratio
      were independently associated with poor exercise capacity in a large cohort of
      patients with sickle cell anemia. Controlled trials investigating whether
      strategies to prevent or delay pulmonary hypertension and/or LV diastolic
      dysfunction will improve exercise capacity and long-term outcomes in sickle cell
      anemia should be considered. Clinical Trial Registration- URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00492531.

PMID- 21900083
TI  - Heart disease may be a risk factor for pulmonary embolism without peripheral deep
      venous thrombosis.
AB  - BACKGROUND: Heart diseases increase the risk of arterial embolism; whether they
      increase the risk of pulmonary embolism without peripheral venous thrombosis is
      less certain. METHODS AND RESULTS: We conducted a nationwide, population-based
      case-control study in Denmark using patients diagnosed with pulmonary embolism
      and/or deep venous thrombosis between 1980 and 2007. We computed odds ratios to
      estimate relative risks associating preceding heart disease with pulmonary
      embolism, pulmonary embolism and deep venous thrombosis, or deep venous
      thrombosis alone. In this study, 45,282 patients had pulmonary embolism alone,
      4680 had pulmonary embolism and deep venous thrombosis, and 59,790 had deep
      venous thrombosis alone; 541,561 were population controls. Myocardial infarction
      and heart failure in the preceding 3 months conferred high risks of apparently
      isolated pulmonary embolism (odds ratio, 43.5 [95% confidence interval (CI), 39.6
      47.8] and 32.4 [95% CI, 29.8-35.2], respectively), whereas the risks of combined
      pulmonary embolism and deep venous thrombosis (19.7 [95% CI, 16.0-24.2] and 22.1
      [95% CI, 18.7-26.0], respectively) and deep venous thrombosis alone (9.6 [95% CI,
      8.6-10.7] and 12.7 [95% CI, 11.6-13.9], respectively) were lower. Left-sided
      valvular disease was associated with an odds ratio of 13.5 (95% CI, 11.3-16.1),
      whereas the odds ratio was 74.6 (95% CI, 28.4-195.8) for right-sided valvular
      disease. Restricting the analysis to cases diagnosed after 2000 led to lower risk
      estimates but the same overall pattern. CONCLUSION: Heart diseases increase the
      near-term risk for pulmonary embolism not associated with diagnosed peripheral
      vein thrombosis.

PMID- 21900084
TI  - Predictors of response to cardiac resynchronization therapy in the Multicenter
      Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy
      (MADIT-CRT).
AB  - BACKGROUND: We hypothesized that combined assessment of factors that are
      associated with favorable reverse remodeling after cardiac resynchronization
      defibrillator therapy (CRT-D) can be used to predict clinical response to the
      device. METHODS AND RESULTS: The study population comprised 1761 patients
      enrolled in the Multicenter Automatic Defibrillator Implantation Trial With
      Cardiac Resynchronization Therapy (MADIT-CRT). Best-subset regression analysis
      was performed to identify factors associated with echocardiographic response
      (defined as percent reduction in left ventricular end-diastolic volume 1 year
      after CRT-D implantation) and to create a response score. Cox proportional
      hazards regression analysis was used to evaluate the CRT-D versus defibrillator
      only reduction in the risk of heart failure or death by the response score. Seven
      factors were identified as associated with echocardiographic response to CRT-D
      and made up the response score (female sex, nonischemic origin, left bundle
      branch block, QRS >=150 milliseconds, prior hospitalization for heart failure,
      left ventricular end-diastolic volume >=125 mL/m(2), and left atrial volume <40
      mL/m(2)). Multivariate analysis showed a 13% (P<0.001) increase in the clinical
      benefit of CRT-D per 1-point increment in the response score (range, 0-14) and a
      significant direct correlation between risk reduction associated with CRT-D and
      response score quartiles: Patients in the first quartile did not derive a
      significant reduction in the risk of heart failure or death with CRT-D (hazard
      ratio=0.87; P=0.52); patients in the second and third quartiles derived 33%
      (P=0.04) and 36% (P=0.03) risk reductions, respectively; and patients in the
      upper quartile experienced a 69% (P<0.001) risk reduction (P for trend=0.005).
      CONCLUSION: Combined assessment of factors associated with reverse remodeling can
      be used for improved selection of patients for cardiac resynchronization therapy.
      Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique
      identifier: NCT00180271.

PMID- 21900085
TI  - Role of cardiovascular magnetic resonance as a gatekeeper to invasive coronary
      angiography in patients presenting with heart failure of unknown etiology.
AB  - BACKGROUND: In patients presenting with new-onset heart failure of uncertain
      etiology, the role of coronary angiography (CA) is unclear. Although
      conventionally performed to differentiate underlying coronary artery disease from
      dilated cardiomyopathy, CA is associated with a risk of complications and may not
      detect an ischemic cause resulting from arterial recanalization or an embolic
      episode. In this study, we assessed the diagnostic accuracy of a cardiovascular
      magnetic resonance (CMR) protocol incorporating late gadolinium enhancement (LGE)
      and magnetic resonance CA as a noninvasive gatekeeper to CA in determining the
      etiology of heart failure in this subset of patients. METHODS AND RESULTS: One
      hundred twenty consecutive patients underwent CMR and CA. The etiology was
      ascribed by a consensus panel that used the results of the CMR scans. Similarly,
      a separate consensus group ascribed an underlying cause by using the results of
      CA. The diagnostic accuracy of both strategies was compared against a gold
      standard panel that made a definitive judgment by reviewing all clinical data.
      The study was powered to show noninferiority between the 2 techniques. The
      sensitivity of 100%, specificity of 96%, and diagnostic accuracy of 97% for LGE
      CMR were equivalent to CA (sensitivity, 93%; specificity, 96%; and diagnostic
      accuracy, 95%). As a gatekeeper to CA, LGE-CMR was also found to be a cheaper
      diagnostic strategy in a decision tree model when United Kingdom-based costs were
      assumed. The economic merits of this model would change, depending on the
      relative costs of LGE-CMR and CA in any specific healthcare system. CONCLUSION:
      This study showed that LGE-CMR is a safe, clinically effective, and potentially
      economical gatekeeper to CA in patients presenting with heart failure of
      uncertain etiology.

PMID- 21900086
TI  - Therapeutic inhibition of miR-208a improves cardiac function and survival during
      heart failure.
AB  - BACKGROUND: Diastolic dysfunction in response to hypertrophy is a major clinical
      syndrome with few therapeutic options. MicroRNAs act as negative regulators of
      gene expression by inhibiting translation or promoting degradation of target
      mRNAs. Previously, we reported that genetic deletion of the cardiac-specific miR
      208a prevents pathological cardiac remodeling and upregulation of Myh7 in
      response to pressure overload. Whether this miRNA might contribute to diastolic
      dysfunction or other forms of heart disease is currently unknown. METHODS AND
      RESULTS: Here, we show that systemic delivery of an antisense oligonucleotide
      induces potent and sustained silencing of miR-208a in the heart. Therapeutic
      inhibition of miR-208a by subcutaneous delivery of antimiR-208a during
      hypertension-induced heart failure in Dahl hypertensive rats dose-dependently
      prevents pathological myosin switching and cardiac remodeling while improving
      cardiac function, overall health, and survival. Transcriptional profiling
      indicates that antimiR-208a evokes prominent effects on cardiac gene expression;
      plasma analysis indicates significant changes in circulating levels of miRNAs on
      antimiR-208a treatment. CONCLUSIONS: These studies indicate the potential of
      oligonucleotide-based therapies for modulating cardiac miRNAs and validate miR
      208 as a potent therapeutic target for the modulation of cardiac function and
      remodeling during heart disease progression.

PMID- 21900088
TI  - Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a
      randomized, placebo-controlled, crossover study in healthy subjects.
AB  - BACKGROUND: Rivaroxaban and dabigatran are new oral anticoagulants that
      specifically inhibit factor Xa and thrombin, respectively. Clinical studies on
      the prevention and treatment of venous and arterial thromboembolism show
      promising results. A major disadvantage of these anticoagulants is the absence of
      an antidote in case of serious bleeding or when an emergency intervention needs
      immediate correction of coagulation. This study evaluated the potential of
      prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of
      these drugs. METHODS AND RESULTS: In a randomized, double-blind, placebo
      controlled study, 12 healthy male volunteers received rivaroxaban 20 mg twice
      daily (n=6) or dabigatran 150 mg twice daily (n=6) for 21/2 days, followed by
      either a single bolus of 50 IU/kg PCC (Cofact) or a similar volume of saline.
      After a washout period, this procedure was repeated with the other anticoagulant
      treatment. Rivaroxaban induced a significant prolongation of the prothrombin time
      (15.8+/-1.3 versus 12.3+/-0.7 seconds at baseline; P<0.001) that was immediately
      and completely reversed by PCC (12.8+/-1.0; P<0.001). The endogenous thrombin
      potential was inhibited by rivaroxaban (51+/-22%; baseline, 92+/-22%; P=0.002)
      and normalized with PCC (114+/-26%; P<0.001), whereas saline had no effect.
      Dabigatran increased the activated partial thromboplastin time, ecarin clotting
      time (ECT), and thrombin time. Administration of PCC did not restore these
      coagulation tests. CONCLUSION: Prothrombin complex concentrate immediately and
      completely reverses the anticoagulant effect of rivaroxaban in healthy subjects
      but has no influence on the anticoagulant action of dabigatran at the PCC dose
      used in this study. Clinical Trial Registration- URL:
      http://www.trialregister.nl. Unique identifier: NTR2272.

PMID- 21900089
TI  - Multimodality imaging in an unusual case of palpitations and right heart failure.

PMID- 21900087
TI  - Mechanisms of myocardial infarction in women without angiographically obstructive
      coronary artery disease.
AB  - BACKGROUND: There is no angiographically demonstrable obstructive coronary artery
      disease (CAD) in a significant minority of patients with myocardial infarction,
      particularly women. We sought to determine the mechanism(s) of myocardial
      infarction in this setting using multiple imaging techniques. METHODS AND
      RESULTS: Women with myocardial infarction were enrolled prospectively, before
      angiography, if possible. Women with >=50% angiographic stenosis or use of
      vasospastic agents were excluded. Intravascular ultrasound was performed during
      angiography; cardiac magnetic resonance imaging was performed within 1 week.
      Fifty women (age, 57+/-13 years) had median peak troponin of 1.60 ng/mL; 11 had
      ST-segment elevation. Median diameter stenosis of the worst lesion was 20% by
      angiography; 15 patients (30%) had normal angiograms. Plaque disruption was
      observed in 16 of 42 patients (38%) undergoing intravascular ultrasound. There
      were abnormal myocardial cardiac magnetic resonance imaging findings in 26 of 44
      patients (59%) undergoing cardiac magnetic resonance imaging, late gadolinium
      enhancement (LGE) in 17 patients, and T2 signal hyperintensity indicating edema
      in 9 additional patients. The most common LGE pattern was ischemic
      (transmural/subendocardial). Nonischemic LGE patterns
      (midmyocardial/subepicardial) were also observed. Although LGE was infrequent
      with plaque disruption, T2 signal hyperintensity was common with plaque
      disruption. CONCLUSIONS: Plaque rupture and ulceration are common in women with
      myocardial infarction without angiographically demonstrable obstructive coronary
      artery disease. In addition, LGE is common in this cohort of women, with an
      ischemic pattern of injury most evident. Vasospasm and embolism are possible
      mechanisms of ischemic LGE without plaque disruption. Intravascular ultrasound
      and cardiac magnetic resonance imaging provide complementary mechanistic insights
      into female myocardial infarction patients without obstructive coronary artery
      disease and may be useful in identifying potential causes and therapies. Clinical
      Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier:
      NCT00798122.

PMID- 21900090
TI  - Cardiology patient page. Nutritional advice for the patient with heart disease:
      what diet should we recommend for our patients?

PMID- 21900092
TI  - Letter by Dimitrow and Cheng regarding article, "Exercise testing in
      nonatherosclerotic heart disease: hypertrophic cardiomyopathy, valvular heart
      disease, and arrhythmias".

PMID- 21900093
TI  - Letter by Deutsch et al regarding article, "Long-term outcomes of endoscopic vein
      harvesting after coronary artery bypass grafting".

PMID- 21900094
TI  - Fish oil for secondary prevention of atrial fibrillation: should we still believe
      in its antiarrhythmic effect?

PMID- 21900095
TI  - The rise and fall of abdominal aortic aneurysm.

PMID- 21900097
TI  - Pulmonary artery intimal sarcoma masquerading as pulmonary embolism.

PMID- 21900096
TI  - New horizons in cardioprotection: recommendations from the 2010 National Heart,
      Lung, and Blood Institute Workshop.

PMID- 21900098
TI  - Bevacizumab-induced reversible posterior leukoencephalopathy syndrome and
      successful retreatment in a patient with glioblastoma.

PMID- 21900099
TI  - Soft-tissue plasmacytomas in multiple myeloma: incidence, mechanisms of
      extramedullary spread, and treatment approach.
AB  - We provide an overview on soft-tissue extramedullary plasmacytomas (EMPs) in
      multiple myeloma (MM). We reviewed the incidence of EMPs in MM, myeloma bone
      marrow homing, possible mechanisms of extramedullary spread, and prognosis and
      response to therapy. The incidence of EMPs is 7% to 18% at MM diagnosis and up to
      20% at relapse. The current notion that EMPs are more frequent after treatment
      with novel agents remains to be proven, especially considering that different
      patterns of disease recurrence can emerge as patients live longer in the era of
      novel drugs. Bone marrow genetic abnormalities are not associated with
      extramedullary spread per se, which also suggests that microenvironmental
      interactions are key. Possible mechanisms of extramedullary spread include
      decreased adhesion molecule expression and downregulation of chemokine receptors.
      EMPs usually show plasmablastic morphology with negative CD56 expression. High
      dose therapy with autologous stem-cell transplantation (ASCT) can overcome the
      negative prognostic impact of extramedullary disease in younger selected
      patients. EMPs do not typically respond to thalidomide alone, but in contrast,
      responses to bortezomib have been reported. The incidence of EMPs in patients
      with MM is high and is associated with poor outcome in patients treated
      conventionally. A potential first-line treatment option seems to be a bortezomib
      containing regimen followed by ASCT, whenever possible. Experimental studies on
      the mechanisms of myeloma cell adhesion, myeloma growth at extramedullary sites,
      and drug sensitivity are priorities for this area of continuing therapeutic
      challenge.

PMID- 21900100
TI  - FOLFIRINOX: a small step or a great leap forward?

PMID- 21900101
TI  - Melanoma staging: implications of histologic sectioning procedures.

PMID- 21900102
TI  - European Treatment and Outcome Study (EUTOS) score for chronic myeloid leukemia
      still requires more confirmation.

PMID- 21900103
TI  - Myxopapillary ependymoma with pleuropulmonary metastases and high plasma glial
      fibrillary acidic protein levels.

PMID- 21900104
TI  - Pharmacogenomic prediction of anthracycline-induced cardiotoxicity in children.
AB  - PURPOSE: Anthracycline-induced cardiotoxicity (ACT) is a serious adverse drug
      reaction limiting anthracycline use and causing substantial morbidity and
      mortality. Our aim was to identify genetic variants associated with ACT in
      patients treated for childhood cancer. PATIENTS AND METHODS: We carried out a
      study of 2,977 single-nucleotide polymorphisms (SNPs) in 220 key drug
      biotransformation genes in a discovery cohort of 156 anthracycline-treated
      children from British Columbia, with replication in a second cohort of 188
      children from across Canada and further replication of the top SNP in a third
      cohort of 96 patients from Amsterdam, the Netherlands. RESULTS: We identified a
      highly significant association of a synonymous coding variant rs7853758 (L461L)
      within the SLC28A3 gene with ACT (odds ratio, 0.35; P = 1.8 * 10(-5) for all
      cohorts combined). Additional associations (P < .01) with risk and protective
      variants in other genes including SLC28A1 and several adenosine triphosphate
      binding cassette transporters (ABCB1, ABCB4, and ABCC1) were present. We further
      explored combining multiple variants into a single-prediction model together with
      clinical risk factors and classification of patients into three risk groups. In
      the high-risk group, 75% of patients were accurately predicted to develop ACT,
      with 36% developing this within the first year alone, whereas in the low-risk
      group, 96% of patients were accurately predicted not to develop ACT. CONCLUSION:
      We have identified multiple genetic variants in SLC28A3 and other genes
      associated with ACT. Combined with clinical risk factors, genetic risk profiling
      might be used to identify high-risk patients who can then be provided with safer
      treatment options.

PMID- 21900105
TI  - 2011 Focused Update of 2009 American Society of Clinical Oncology Clinical
      Practice Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung
      Cancer.
AB  - PURPOSE: An American Society of Clinical Oncology (ASCO) focused update updates a
      single recommendation (or subset of recommendations) in advance of a regularly
      scheduled guideline update. This document updates one recommendation of the ASCO
      Guideline Update on Chemotherapy for Stage IV Non-Small-Cell Lung Cancer (NSCLC)
      regarding switch maintenance chemotherapy. CLINICAL CONTEXT: Recent results from
      phase III clinical trials have demonstrated that in patients with stage IV NSCLC
      who have received four cycles of first-line chemotherapy and whose disease has
      not progressed, an immediate switch to alternative, single-agent chemotherapy can
      extend progression-free survival and, in some cases, overall survival. Because of
      limitations in the data, delayed treatment with a second-line agent after disease
      progression is also acceptable. RECENT DATA: Seven randomized controlled trials
      of carboxyaminoimidazole, docetaxel, erlotinib, gefitinib, gemcitabine, and
      pemetrexed have evaluated outcomes in patients who received an immediate, non
      cross resistant alternative therapy (switch maintenance) after first-line
      therapy. RECOMMENDATION: In patients with stage IV NSCLC, first-line cytotoxic
      chemotherapy should be stopped at disease progression or after four cycles in
      patients whose disease is stable but not responding to treatment. Two-drug
      cytotoxic combinations should be administered for no more than six cycles. For
      those with stable disease or response after four cycles, immediate treatment with
      an alternative, single-agent chemotherapy such as pemetrexed in patients with
      nonsquamous histology, docetaxel in unselected patients, or erlotinib in
      unselected patients may be considered. Limitations of this data are such that a
      break from cytotoxic chemotherapy after a fixed course is also acceptable, with
      initiation of second-line chemotherapy at disease progression.

PMID- 21900107
TI  - Flaxseed and breast cancer: what should we tell our patients?

PMID- 21900106
TI  - Response to neoadjuvant systemic therapy for breast cancer in BRCA mutation
      carriers and noncarriers: a single-institution experience.
AB  - PURPOSE: To compare the pathologic complete response (pCR) rate and relapse-free
      survival (RFS) and overall survival (OS) after neoadjuvant systemic chemotherapy
      (NST) in patients with breast cancer with and without deleterious BRCA1 and BRCA2
      mutations. PATIENTS AND METHODS: A total of 317 women who underwent BRCA genetic
      testing and were treated with NST for breast cancer between 1997 and 2009 were
      included in the study. The Kaplan-Meier product-limit method was used to estimate
      RFS and OS rates. Logistic regression models were fit to determine the
      associations between BRCA status, pCR, and survival. RESULTS: Fifty-seven (18%)
      and 23 (7%) patients had BRCA1 and BRCA2 mutations, respectively. Twenty-six
      (46%) of 57 BRCA1 carriers achieved a pCR, compared with three (13%) of 23 BRCA2
      carriers and 53 (22%) of 237 BRCA noncarriers (P < .001). In the multivariate
      logistic model, BRCA1 status (odds ratio [OR] = 3.16; 95% CI, 1.55 to 6.42; P =
      .002), estrogen receptor (ER) negativity (OR = 1.96; 95% CI:1.05 to 3.65; P =
      .03) and concurrent trastuzumab use (OR = 4.18; 95% CI, 2.04 to 8.57; P < .001)
      remained as independent significant predictors for a pCR. At a median follow-up
      of 3.2 years, 69 patients (22%) experienced a disease recurrence or death. No
      significant differences were noted in survival outcomes with respect to BRCA
      status and type of NST received. However, among BRCA1 carriers, patients who
      achieved a pCR had better 5-year RFS (P = .001) and OS (P = .01) rates than
      patients who did not. CONCLUSION: BRCA1 status and ER negativity are
      independently associated with higher pCR rates in patients with breast cancer.
      Overall prognosis of breast cancer in BRCA carriers is similar to sporadic breast
      cancers.

PMID- 21900108
TI  - Should the presence of germline BRCA1/2 mutations influence treatment selection
      in breast cancer?

PMID- 21900109
TI  - Parathyroid carcinoma: a rare case report.

PMID- 21900110
TI  - Prostatic urethral recurrence of urachal adenocarcinoma.

PMID- 21900111
TI  - "Unfit" for Cisplatin: on basis of which GFR?

PMID- 21900112
TI  - American Society of Clinical Oncology endorsement of the cancer care Ontario
      practice guideline on adjuvant ovarian ablation in the treatment of premenopausal
      women with early-stage invasive breast cancer.
AB  - PURPOSE: The American Society of Clinical Oncology (ASCO) has policies and
      procedures for endorsing practice guidelines that have been developed by other
      professional organizations. METHODS: The Cancer Care Ontario (CCO) Guideline on
      Adjuvant Ovarian Ablation (OA) in the Treatment of Premenopausal Women With Early
      Stage Invasive Breast Cancer was reviewed for developmental rigor by
      methodologists. An ad hoc review panel of experts reviewed the content. RESULTS:
      The ASCO ad hoc OA guideline review panel concurred that the recommendations are
      clear, thorough, based on the most relevant scientific evidence in this content
      area, and present options that will be acceptable to patients. According to the
      CCO guideline: one, OA should not be routinely added to systemic therapy with
      chemotherapy, tamoxifen, or the combination of tamoxifen and chemotherapy; two,
      OA alone is not recommended as an alternative to any other form of systemic
      therapy, except in the specific case of patients who are candidates for other
      forms of systemic therapy but who, for some reason, will not receive any other
      systemic therapy (eg, patients who cannot tolerate other forms of systemic
      therapy or patients who choose no other form of systemic therapy); and three,
      when chemical suppression using luteinizing hormone-releasing hormone agonists is
      the chosen method of OA, in the opinion of the Breast Cancer Disease Site Group,
      monthly injection is the recommended mode of administration. The mode of
      administration in nearly all of the available trials has been monthly
      administration. CONCLUSION: The ASCO review panel agrees with the recommendations
      as stated in the CCO guideline, with the qualification that ongoing research
      studies may alter the recommendations of the panel.

PMID- 21900113
TI  - Phase I pharmacokinetic and pharmacodynamic dose-escalation study of RG7160
      (GA201), the first glycoengineered monoclonal antibody against the epidermal
      growth factor receptor, in patients with advanced solid tumors.
AB  - PURPOSE: We conducted a phase I dose-escalation study to characterize the safety,
      efficacy, pharmacokinetic (PK), and pharmacodynamic properties of RG7160 (GA201),
      a humanized and glycoengineered immunoglobulin G(1) anti-epidermal growth factor
      receptor (EGFR) monoclonal antibody with enhanced antibody-dependent cell
      mediated cytotoxicity. PATIENTS AND METHODS: Seventy-five patients with advanced
      EGFR-positive solid tumors received RG7160 (50 to 1,400 mg) administered every
      week, every 2 weeks, or every 3 weeks. Dose escalation followed a three-plus
      three trial design. RESULTS: No maximum-tolerated dose was reached for any dosing
      schedule. Common adverse events (AEs) included rash (80% of patients), infusion
      related reactions (77%), and hypomagnesemia (56%). Grades 3 and 4 AEs were rash
      (grade 3, 25%), infusion-related reaction (grade 3, 7%; grade 4, 1%), paronychia
      (grade 3, 3%), and hypomagnesemia (grade 3, 1%; grade 4, 1%). RG7160 exposure
      increased greater than proportionally over the 50- to 400-mg dose range (with
      greater than proportional decline in clearance) and approximately dose
      proportionally above 400 mg (where clearance plateaued). A marked reduction in
      circulating natural killer cells and increased infiltration of immune effector
      cells into skin rash were seen. Clinical efficacy included one complete response
      and two partial responses in patients with colorectal cancer (including one with
      KRAS mutation) and disease stabilization in 27 patients. CONCLUSION: RG7160 had
      an acceptable safety profile with manageable AEs and demonstrated promising
      efficacy in this heavily pretreated patient cohort. On the basis of modeling of
      available PK parameters, the RG7160 dose selected for part two of this study is
      1,400 mg on days 1 and 8 followed by 1,400 mg every 2 weeks.

PMID- 21900114
TI  - Age, breast cancer subtype approximation, and local recurrence after breast
      conserving therapy.
AB  - PURPOSE: Prior results of breast-conserving therapy (BCT) have shown substantial
      rates of local recurrence (LR) in young patients with breast cancer (BC).
      PATIENTS AND METHODS: We studied 1,434 consecutive patients with invasive BC who
      received BCT from December 1997 to July 2006. Ninety-one percent received
      adjuvant systemic therapy; no patients received trastuzumab. Five BC subtypes
      were approximated: estrogen receptor (ER) or progesterone receptor (PR) positive,
      HER2 negative, and grades 1 to 2 (ie, luminal A); ER positive or PR positive,
      HER2 negative, and grade 3 (ie, luminal B); ER or PR positive, and HER2 positive
      (ie, luminal HER2); ER negative, PR negative, and HER2 positive (ie, HER2); and
      ER negative, PR negative, and HER2 negative (ie, triple negative). Actuarial
      rates of LR were calculated by using the Kaplan-Meier method. RESULTS: Median
      follow-up was 85 months. Overall 5-year cumulative incidence of LR was 2.1% (95%
      CI, 1.4% to 3.0%). The 5-year cumulative incidence of LR was 5.0% (95% CI, 3.0%
      to 8.3%) for age quartile 23 to 46 years; 2.2% (95% CI, 1.0% to 4.6%) for ages 47
      to 54 years; 0.9% (95% CI, 0.3% to 2.6%) for ages 55 to 63 years; and 0.6% (95%
      CI, 0.1% to 2.2%) for ages 64 to 88 years. The 5-year cumulative incidence of LR
      was 0.8% (95% CI, 0.4% to 1.8%) for luminal A; 2.3% (95% CI, 0.8% to 5.9%) for
      luminal B; 1.1% (95% CI, 0.2% 7.4%) for luminal HER2; 10.8% (95% CI, 4.6% to
      24.4%) for HER2; and 6.7% (95% CI, 3.6% to 12.2%) for triple negative. On
      multivariable analysis, increasing age was associated with decreased risk of LR
      (adjusted hazard ratio, 0.97; 95% CI, 0.94 to 0.99; P = .009). CONCLUSION: In the
      era of systemic therapy and BC subtyping, age remains an independent prognostic
      factor after BCT. However, the risk of LR for young women appears acceptably low.

PMID- 21900115
TI  - Serum enterolactone and prognosis of postmenopausal breast cancer.
AB  - PURPOSE: Lignans--plant-derived compounds with estrogen-dependent and 
      independent anticarcinogenic properties--have been associated with postmenopausal
      breast cancer risk, but data are limited regarding their effect on survival.
      Dietary lignans are metabolized to enterolignans, which are subsequently absorbed
      and become bioavailable. PATIENTS AND METHODS: We assessed the prognosis of 1,140
      postmenopausal patients with breast cancer age 50 to 74 years who were diagnosed
      between 2002 and 2005. Vital status through the end of 2009 was ascertained via
      local population registries, and deaths were verified by death certificates.
      Information on recurrences and secondary tumors was verified by clinical records
      and attending physicians. Associations of postdiagnostic serum enterolactone (a
      biomarker for dietary lignans) with overall survival and distant disease-free
      survival were assessed by using Cox proportional hazards models stratified by age
      at diagnosis and adjusted for prognostic factors. RESULTS: Median enterolactone
      levels for deceased patients and those still alive were 17.0 and 21.4 nmol/L,
      respectively. During a median of 6.1 years of follow-up after diagnosis, 162
      deaths were confirmed. Higher serum enterolactone levels were associated with
      significantly reduced hazard ratios (HRs) for death (HR per 10 nmol/L increment,
      0.94; P = .04; HR for the highest quartile, 0.58; 95% CI, 0.34 to 0.99). For
      distant disease, HR was 0.94 per 10 nmol/L increment (P = .08) and 0.62 (95% CI,
      0.35 to 1.09) for the highest quartile. The highest quartile of serum
      enterolactone was associated with a significantly reduced risk of death only for
      estrogen receptor-negative tumors (HR, 0.27; 95% CI, 0.08 to 0.87) but not for
      estrogen receptor-positive tumors (HR, 0.91; 95% CI, 0.45 to 1.84: P for
      heterogeneity = .09). CONCLUSION: Postmenopausal patients with breast cancer who
      have high serum enterolactone levels may have better survival.

PMID- 21900116
TI  - Transient blood transfusion reaction masquerading as a post-transplantation
      lymphoproliferative disorder mimicking acute leukemia cutis.

PMID- 21900117
TI  - Improved evidence will support sound decision making but will not solve the
      problem of cost containment in oncology.

PMID- 21900118
TI  - Cervical cancer prevention: better tests, better tools, and more equitable
      outcomes.

PMID- 21900119
TI  - Persistence of type-specific human papillomavirus infection and increased long
      term risk of cervical cancer.
AB  - BACKGROUND: Human papillomavirus (HPV) persistence is the pivotal event in
      cervical carcinogenesis. We followed a large-scale community-based cohort for 16
      years to investigate the role of genotype-specific HPV persistence in predicting
      cervical cancer including invasive and in situ carcinoma. METHODS: At the
      baseline examination in 1991-1992, 11,923 participants (aged 30-65 years)
      consented to HPV testing and cytology; 6923 participants were reexamined in 1993
      1995. For HPV testing, we used a polymerase chain reaction-based assay that
      detected 39 HPV types. Women who developed cervical cancer were identified from
      cancer and death registries. Cumulative risks for developing cervical cancer
      among infected and persistently infected women were calculated by the Kaplan
      Meier method. RESULTS: Of 10,123 women who were initially cytologically normal,
      68 developed cervical cancer. The 16-year cumulative risks of subsequent cervical
      cancer for women with HPV16, HPV58 (without HPV16), or other carcinogenic HPV
      types (without HPV16 or HPV58) were 13.5%, 10.3%, and 4.0%, respectively,
      compared with 0.26% for HPV-negative women. Women with type-specific persistence
      of any carcinogenic HPV had greatly increased risk compared with women who were
      HPV-negative at both visits (hazard ratio = 75.4, 95% confidence interval = 31.8
      to 178.9). The cumulative cervical cancer risks following persistent carcinogenic
      HPV infections increased with age: The risks were 5.5%, 14.4%, and 18.1% for
      women aged 30-44 years, 45-54 years, and 55 years and older, respectively.
      However, newly acquired infections were associated with a low risk of cervical
      cancer regardless of age. CONCLUSIONS: HPV negativity was associated with a very
      low long-term risk of cervical cancer. Persistent detection of HPV among
      cytologically normal women greatly increased risk. Thus, it is useful to perform
      repeated HPV testing following an initial positive test.

PMID- 21900120
TI  - Model-based analyses to compare health and economic outcomes of cancer control:
      inclusion of disparities.
AB  - BACKGROUND: Disease simulation models of the health and economic consequences of
      different prevention and treatment strategies can guide policy decisions about
      cancer control. However, models that also consider health disparities can
      identify strategies that improve both population health and its equitable
      distribution. METHODS: We devised a typology of cancer disparities that considers
      types of inequalities among black, white, and Hispanic populations across
      different cancers and characteristics important for near-term policy discussions.
      We illustrated the typology in the specific example of cervical cancer using an
      existing disease simulation model calibrated to clinical, epidemiological, and
      cost data for the United States. We calculated average reduction in cancer
      incidence overall and for black, white, and Hispanic women under five different
      prevention strategies (Strategies A1, A2, A3, B, and C) and estimated average
      costs and life expectancy per woman, and the cost-effectiveness ratio for each
      strategy. RESULTS: Strategies that may provide greater aggregate health benefit
      than existing options may also exacerbate disparities. Combining human
      papillomavirus vaccination (Strategy A2) with current cervical cancer screening
      patterns (Strategy A1) resulted in an average reduction of 69% in cancer
      incidence overall but a 71.6% reduction for white women, 68.3% for black women,
      and 63.9% for Hispanic women. Other strategies targeting risk-based screening to
      racial and ethnic minorities reduced disparities among racial subgroups and
      resulted in more equitable distribution of benefits among subgroups (reduction in
      cervical cancer incidence, white vs. Hispanic women, 69.7% vs. 70.1%). Strategies
      that employ targeted risk-based screening and new screening algorithms, with or
      without vaccination (Strategies B and C), provide excellent value. The most
      effective strategy (Strategy C) had a cost-effectiveness ratio of $28,200 per
      year of life saved when compared with the same strategy without vaccination.
      CONCLUSIONS: We identify screening strategies for cervical cancer that provide
      greater aggregate health benefit than existing options, offer excellent cost
      effectiveness, and have the biggest positive impact in worst-off groups. The
      typology proposed here may also be useful in research and policy decisions when
      trade-offs between fairness and cost-effectiveness are unavoidable.

PMID- 21900121
TI  - Delayed bone regeneration and low bone mass in a rat model of insulin-resistant
      type 2 diabetes mellitus is due to impaired osteoblast function.
AB  - Patients with diabetes mellitus have an impaired bone metabolism; however, the
      underlying mechanisms are poorly understood. Here, we analyzed the impact of type
      2 diabetes mellitus on bone physiology and regeneration using Zucker diabetic
      fatty (ZDF) rats, an established rat model of insulin-resistant type 2 diabetes
      mellitus. ZDF rats develop diabetes with vascular complications when fed a
      Western diet. In 21-wk-old diabetic rats, bone mineral density (BMD) was 22.5%
      (total) and 54.6% (trabecular) lower at the distal femur and 17.2% (total) and
      20.4% (trabecular) lower at the lumbar spine, respectively, compared with
      nondiabetic animals. BMD distribution measured by backscattered electron imaging
      postmortem was not different between diabetic and nondiabetic rats, but
      evaluation of histomorphometric indexes revealed lower mineralized bone
      volume/tissue volume, trabecular thickness, and trabecular number. Osteoblast
      differentiation of diabetic rats was impaired based on lower alkaline phosphatase
      activity (-20%) and mineralized matrix formation (-55%). In addition, the
      expression of the osteoblast-specific genes bone morphogenetic protein-2, RUNX2,
      osteocalcin, and osteopontin was reduced by 40-80%. Osteoclast biology was not
      affected based on tartrate-resistant acidic phosphatase staining, pit formation
      assay, and gene profiling. To validate the implications of these molecular and
      cellular findings in a clinically relevant model, a subcritical bone defect of 3
      mm was created at the left femur after stabilization with a four-hole plate, and
      bone regeneration was monitored by X-ray and microcomputed tomography analyses
      over 12 wk. While nondiabetic rats filled the defects by 57%, diabetic rats
      showed delayed bone regeneration with only 21% defect filling. In conclusion, we
      identified suppressed osteoblastogenesis as a cause and mechanism for low bone
      mass and impaired bone regeneration in a rat model of type 2 diabetes mellitus.

PMID- 21900122
TI  - Increased maternal fat consumption during pregnancy alters body composition in
      neonatal mice.
AB  - Maternal overnutrition prior to and during gestation causes pronounced metabolic
      dysfunction in the adult offspring. However, less is known about metabolic
      adaptations in the offspring that occur independently of postnatal growth and
      nutrition. Therefore, we evaluated the impact of excess maternal dietary lipid
      intake on the in utero programming of body composition, hepatic function, and
      hypothalamic development in newborn (P0) offspring. Female mice were fed a low
      fat (LF) or high-fat (HF) diet and were mated after 4, 12, and 23 wk. A subset of
      the obese HF dams was switched to the LF diet during the second (DR2) or third
      (DR3) pregnancies. The HF offspring accrued more fat mass than the LF pups,
      regardless of duration of maternal HF diet consumption or prepregnancy maternal
      adiposity. Increased neonatal adiposity was not observed in the DR3 pups. Liver
      weights were reduced in the HF offspring but not in the DR2 or DR3 pups.
      Offspring hepatic triglyceride content was reduced in the HF pups, but hepatic
      inflammation and expression of lipid metabolism genes were largely unaffected by
      maternal diet. Maternal diet did not alter the hypothalamic expression of
      orexigenic and anorexigenic neuropeptides in the offspring. Thus, the
      intrauterine programming of increased neonatal adiposity and reduced liver size
      by maternal overnutrition is evident in mice at birth and occurs prior to the
      development of maternal obesity. These observations demonstrate that dietary
      intervention during pregnancy minimizes the deleterious effects of maternal
      obesity on offspring body composition, potentially reducing the offsprings' risk
      of developing obesity and related diseases later in life.

PMID- 21900123
TI  - Globular adiponectin counteracts VCAM-1-mediated monocyte adhesion via AdipoR1/NF
      kappaB/COX-2 signaling in human aortic endothelial cells.
AB  - Adiponectin (Ad) is an insulin-sensitizing adipocytokine with anti-inflammatory
      and vasoprotective properties. Cleavage of native full-length Ad (fAd) by
      elastases from activated monocytes generates globular Ad (gAd). Increased gAd
      levels are observed in the proximity of atherosclerotic lesions, but the
      physiological meaning of this proteolytic Ad fragment in the cardiovascular
      system is controversial. We compared molecular and biological properties of fAd
      and gAd in human aortic endothelial cells (HAEC). In control HAEC, both fAd and
      gAd acutely stimulated nitric oxide (NO) production by AMPK-dependent pathways.
      With respect to fAd, gAd more efficiently increased activation of NF-kappaB
      signaling pathways, resulting in cyclooxygenase-2 (COX-2) overexpression and COX
      2-dependent prostacyclin 2 (PGI(2)) release. In contrast with fAd, gAd also
      increased p38 MAPK phosphorylation and VCAM-1 expression, ultimately enhancing
      adhesion of monocytes to endothelial cells. In HAEC lacking AdipoR1 (by siRNA),
      both activation of NF-kappaB as well as COX-2 overexpression by gAd were
      abrogated. Conversely, gAd-mediated p38MAPK activation and VCAM-1 expression were
      unaffected, and monocyte adhesion was greatly enhanced. In HAEC lacking COX-2 (by
      siRNA), reduced levels of PGI(2) further increased gAd-dependent monocyte
      adhesion. Our findings suggest that biological activities of fAd and gAd in
      endothelium do not completely overlap, with gAd possessing both AdipoR1-dependent
      ability to stimulate COX-2 expression and AdipoR1-independent effects related to
      expression of VCAM-1 and adhesion of monocytes to endothelium.

PMID- 21900124
TI  - Oscillations in joint synchrony of reproductive hormones in healthy men.
AB  - Negative-feedback (inhibitory) and positive-feedforward (stimulatory) processes
      regulate physiological systems. Whether such processes are themselves rhythmic is
      not known. Here, we apply cross-approximate entropy (cross-ApEn), a noninvasive
      measurement of joint (pairwise) signal synchrony, to inferentially assess
      hypothesized circadian and ultradian variations in feedback coupling. The data
      comprised simultaneous measurements of three pituitary and one peripheral hormone
      (LH, FSH, prolactin, and testosterone) in 12 healthy men each sampled every 10
      min for 4 days (5,760 min). Ergodicity, due to the time series stationarity of
      the measurements over the 4 days, allows for effective estimation of parameters
      based upon the 12 subjects. Cross-ApEn changes were quantified via moving-window
      estimates applied to 4-day time series pairs. The resultant ordered windowed
      cross-ApEn series (in time) were subjected to power spectrum analysis.
      Rhythmicity was assessed against the null hypothesis of randomness using 1,000
      simulated periodograms derived by shuffling the interpulse-interval hormone
      concentration segments and redoing cross-ApEn windows and spectral analysis. By
      forward cross-ApEn analysis, paired LH-testosterone, LH-prolactin, and LH-FSH
      synchrony maintained dominant rhythms with periodicities of 18-22.5, 18, and 22.5
      h, respectively (each P < 0.001). By reverse (feedback) cross-ApEn analysis,
      testosterone-LH, testosterone-prolactin, and testosterone-FSH synchrony cycles
      were 30, 18, and 30-45 h, respectively (each P <= 0.001). Significant 8- or 24-h
      rhythms were also detected in most linkages, and maximal bihormonal synchrony
      occurred consistently at ~0400-0500. Collectively, these analyses demonstrate
      significant ultradian (<24 h), circadian (~24 h), and infradian (>24 h)
      oscillations in pituitary-testis synchrony, wherein maximal biglandular
      coordination is strongly constrained to the early morning hours.

PMID- 21900125
TI  - Plasma PTX3 protein levels inversely correlate with insulin secretion and
      obesity, whereas visceral adipose tissue PTX3 gene expression is increased in
      obesity.
AB  - Plasma acutephase protein pentraxin 3 (PTX3) concentration is dysregulated in
      human obesity and metabolic syndrome. Here, we explore its relationship with
      insulin secretion and sensitivity, obesity markers, and adipose tissue PTX3 gene
      expression. Plasma PTX3 protein levels were analyzed in a cohort composed of 27
      lean [body mass index (BMI) <= 25 kg/m(2)] and 48 overweight (BMI 25-30 kg/m(2))
      men (cohort 1). In this cohort, plasma PTX3 was negatively correlated with
      fasting triglyceride levels and insulin secretion after intravenous and oral
      glucose administration. Plasma PTX3 protein and PTX3 gene expression in visceral
      (VAT) and subcutaneous (SAT) whole adipose tissue and adipocyte and
      stromovascular fractions were analyzed in cohort 2, which was composed of 19
      lean, 28 overweight, and 15 obese subjects (BMI >30 kg/m(2)). An inverse
      association with body weight and waist/hip ratio was observed in cohort 2. In VAT
      depots, PTX3 mRNA levels were higher in subjects with BMI >25 kg/m(2) than in
      lean subjects, positively correlated with IL-1beta mRNA levels, and higher in the
      adipocyte than stromovascular fraction. Human preadipocyte SGBS cell line was
      used to study PTX3 production in response to factors that obesity entails. In
      SGBS adipocytes, PTX3 gene expression was enhanced by IL-1beta and TNFalpha but
      not IL-6 or insulin. In conclusion, the negative correlation between PTX3 and
      glucose-stimulated insulin secretion suggests a role for PTX3 in metabolic
      control. PTX3 gene expression is upregulated in VAT depots in obesity, despite
      lower plasma PTX3 protein, and by some proinflammatory cytokines in cultured
      adipocytes.

PMID- 21900127
TI  - The cover. Detail of The Philharmonic.

PMID- 21900128
TI  - A piece of my mind. The mechanics of reasoning.

PMID- 21900126
TI  - Adrenal androgen concentrations increase during infancy in male rhesus macaques
      (Macaca mulatta).
AB  - This study investigated adrenal androgens (AA), gonadotropins, and cortisol in
      castrated and gonad-intact male rhesus macaques from birth through infancy. Blood
      samples were collected longitudinally from castrated (n = 6; weekly, 1-40 wk) and
      intact (n = 4; every other week, 1-17 wk) males. Plasma concentrations of AA were
      determined by liquid chromatography-tandem mass spectrometry, and plasma
      concentrations of cortisol and gonadotropins were determined by RIA.
      Dehydroepiandrosterone sulfate (DHEAS) concentrations increased almost threefold
      (to 8 wk), dehydroepiandrosterone (DHEA) increased more than eightfold (to 11
      wk), and androstenedione doubled (to 15 wk) in five castrated infant males and
      declined continuously thereafter. A sixth castrated male had markedly different
      temporal patterns and concentrations (many times more than 2 SDs from the cohort
      mean) of AA and gonadotropins from first sampling (3 wk) and was excluded from
      analysis. Cortisol increased over 16 wk but correlated poorly with DHEAS.
      Luteinizing and follicle-stimulating hormones increased to peaks at 3 and 7 wk,
      respectively. Testis-intact males exhibited similar profiles, but with earlier
      peaks of DHEAS (5 wk) and DHEA and androstenedione (7 wk). Peak concentrations of
      DHEAS were lower and those of DHEA and androstenedione were higher in intact than
      castrated infants. Testosterone was undetectable in castrated males and >0.5
      ng/ml in intact males but was not correlated with DHEA or DHEAS. These are the
      first data documenting a transient increase in AA secretion during infancy in an
      Old World primate and are consistent with the previously documented time course
      of zona reticularis development that accompanies increases in androgen synthetic
      capacity of the adrenal. The rhesus is a promising model for androgen secretion
      from the human adrenal cortex.

PMID- 21900129
TI  - Emergency department closures in the United States.

PMID- 21900130
TI  - Mental illness and firearm violence.

PMID- 21900131
TI  - Mental illness and firearm violence.

PMID- 21900132
TI  - US medical students' health insurance coverage for mental health and substance
      abuse treatment.

PMID- 21900133
TI  - Clinical protocols and trainee knowledge about mechanical ventilation.
AB  - CONTEXT: Clinical protocols are associated with improved patient outcomes;
      however, they may negatively affect medical education by removing trainees from
      clinical decision making. OBJECTIVE: To study the relationship between critical
      care training with mechanical ventilation protocols and subsequent knowledge
      about ventilator management. DESIGN, SETTING, AND PARTICIPANTS: A retrospective
      cohort equivalence study, linking a national survey of mechanical ventilation
      protocol availability in accredited US pulmonary and critical care fellowship
      programs with knowledge about mechanical ventilation among first-time examinees
      of the American Board of Internal Medicine (ABIM) Critical Care Medicine
      Certification Examination in 2008 and 2009. Exposure to protocols was defined as
      high intensity if an examinee's training intensive care unit had 2 or more
      protocols for at least 3 years and as low intensity if 0 or 1 protocol. MAIN
      OUTCOME MEASURES: Knowledge, measured by performance on examination questions
      specific to mechanical ventilation management, calculated as a mechanical
      ventilation score using item response theory. The score is standardized to a mean
      (SD) of 500 (100), and a clinically important difference is defined as 25.
      Variables included in adjusted analyses were birth country, residency training
      country, and overall first-attempt score on the ABIM Internal Medicine
      Certification Examination. RESULTS: Ninety of 129 programs (70%) responded to the
      survey. Seventy-seven programs (86%) had protocols for ventilation liberation, 66
      (73%) for sedation management, and 54 (60%) for lung-protective ventilation at
      the time of the survey. Eighty-eight (98%) of these programs had trainees who
      completed the ABIM Critical Care Medicine Certification Examination, totaling 553
      examinees. Of these 88 programs, 27 (31%) had 0 protocols, 19 (22%) had 1
      protocol, 24 (27%) had 2 protocols, and 18 (20%) had 3 protocols for at least 3
      years. Forty-two programs (48%) were classified as high intensity and 46 (52%) as
      low intensity, with 304 trainees (55%) and 249 trainees (45%), respectively. In
      bivariable analysis, no difference in mean scores was observed in high-intensity
      (497; 95% CI, 486-507) vs low-intensity programs (497; 95% CI, 485-509). Mean
      difference was 0 (95% CI, -16 to 16), with a positive value indicating a higher
      score in the high-intensity group. In multivariable analyses, no association of
      training was observed in a high-intensity program with mechanical ventilation
      score (adjusted mean difference, -5.36; 95% CI, -20.7 to 10.0). CONCLUSION: Among
      first-time ABIM Critical Care Medicine Certification Examination examinees,
      training in a high-intensity ventilator protocol environment compared with a low
      intensity environment was not associated with worse performance on examination
      questions about mechanical ventilation management.

PMID- 21900134
TI  - Association of unconscious race and social class bias with vignette-based
      clinical assessments by medical students.
AB  - CONTEXT: Studies involving physicians suggest that unconscious bias may be
      related to clinical decision making and may predict poor patient-physician
      interaction. The presence of unconscious race and social class bias and its
      association with clinical assessments or decision making among medical students
      is unknown. OBJECTIVE: To estimate unconscious race and social class bias among
      first-year medical students and investigate its relationship with assessments
      made during clinical vignettes. DESIGN, SETTING, AND PARTICIPANTS: A secure Web
      based survey was administered to 211 medical students entering classes at Johns
      Hopkins School of Medicine, Baltimore, Maryland, in August 2009 and August 2010.
      The survey included the Implicit Association Test (IAT) to assess unconscious
      preferences, direct questions regarding students' explicit race and social class
      preferences, and 8 clinical assessment vignettes focused on pain assessment,
      informed consent, patient reliability, and patient trust. Adjusting for student
      demographics, multiple logistic regression was used to determine whether
      responses to the vignettes were associated with unconscious race or social class
      preferences. MAIN OUTCOME MEASURES: Association of scores on an established IAT
      for race and a novel IAT for social class with vignette responses. RESULTS: Among
      the 202 students who completed the survey, IAT responses were consistent with an
      implicit preference toward white persons among 140 students (69%, 95% CI, 61%
      75%). Responses were consistent with a preference toward those in the upper class
      among 174 students (86%, 95% CI, 80%-90%). Assessments generally did not vary by
      patient race or occupation, and multivariable analyses for all vignettes found no
      significant relationship between implicit biases and clinical assessments.
      Regression coefficient for the association between pain assessment and race IAT
      scores was -0.49 (95% CI, -1.00 to 0.03) and for social class, the coefficient
      was -0.04 (95% CI, -0.50 to 0.41). Adjusted odds ratios for other vignettes
      ranged from 0.69 to 3.03 per unit change in IAT score, but none were
      statistically significant. Analysis stratified by vignette patient race or class
      status yielded similarly negative results. Tests for interactions between patient
      race or class status and student IAT D scores in predicting clinical assessments
      were not statistically significant. CONCLUSIONS: The majority of first-year
      medical students at a single school had IAT scores consistent with implicit
      preference for white persons and possibly for those in the upper class. However,
      overall vignette-based clinical assessments were not associated with patient race
      or occupation, and no association existed between implicit preferences and the
      assessments.

PMID- 21900135
TI  - Quality of life, burnout, educational debt, and medical knowledge among internal
      medicine residents.
AB  - CONTEXT: Physician distress is common and has been associated with negative
      effects on patient care. However, factors associated with resident distress and
      well-being have not been well described at a national level. OBJECTIVES: To
      measure well-being in a national sample of internal medicine residents and to
      evaluate relationships with demographics, educational debt, and medical
      knowledge. DESIGN, SETTING, AND PARTICIPANTS: Study of internal medicine
      residents using data collected on 2008 and 2009 Internal Medicine In-Training
      Examination (IM-ITE) scores and the 2008 IM-ITE survey. Participants were 16,394
      residents, representing 74.1% of all eligible US internal medicine residents in
      the 2008-2009 academic year. This total included 7743 US medical graduates and
      8571 international medical graduates. MAIN OUTCOME MEASURES: Quality of life
      (QOL) and symptoms of burnout were assessed, as were year of training, sex,
      medical school location, educational debt, and IM-ITE score reported as
      percentage of correct responses. RESULTS: Quality of life was rated "as bad as it
      can be" or "somewhat bad" by 2402 of 16,187 responding residents (14.8%). Overall
      burnout and high levels of emotional exhaustion and depersonalization were
      reported by 8343 of 16,192 (51.5%), 7394 of 16,154 (45.8%), and 4541 of 15,737
      (28.9%) responding residents, respectively. In multivariable models, burnout was
      less common among international medical graduates than among US medical graduates
      (45.1% vs 58.7%; odds ratio, 0.70 [99% CI, 0.63-0.77]; P < .001). Greater
      educational debt was associated with the presence of at least 1 symptom of
      burnout (61.5% vs 43.7%; odds ratio, 1.72 [99% CI, 1.49-1.99]; P < .001 for debt
      >$200,000 relative to no debt). Residents reporting QOL "as bad as it can be" and
      emotional exhaustion symptoms daily had mean IM-ITE scores 2.7 points (99% CI,
      1.2-4.3; P < .001) and 4.2 points (99% CI, 2.5-5.9; P < .001) lower than those
      with QOL "as good as it can be" and no emotional exhaustion symptoms,
      respectively. Residents reporting debt greater than $200,000 had mean IM-ITE
      scores 5.0 points (99% CI, 4.4-5.6; P < .001) lower than those with no debt.
      These differences were similar in magnitude to the 4.1-point (99% CI, 3.9-4.3)
      and 2.6-point (99% CI, 2.4-2.8) mean differences associated with progressing from
      first to second and second to third years of training, respectively. CONCLUSIONS:
      In this national study of internal medicine residents, suboptimal QOL and
      symptoms of burnout were common. Symptoms of burnout were associated with higher
      debt and were less frequent among international medical graduates. Low QOL,
      emotional exhaustion, and educational debt were associated with lower IM-ITE
      scores.

PMID- 21900136
TI  - Factors associated with American Board of Medical Specialties member board
      certification among US medical school graduates.
AB  - CONTEXT: Certification by an American Board of Medical Specialties (ABMS) member
      board is emerging as a measure of physician quality. OBJECTIVE: To identify
      demographic and educational factors associated with ABMS member board
      certification of US medical school graduates. DESIGN, SETTING, AND PARTICIPANTS:
      Retrospective study of a national cohort of 1997-2000 US medical school
      graduates, grouped by specialty choice at graduation and followed up through
      March 2, 2009. In separate multivariable logistic regression models for each
      specialty category, factors associated with ABMS member board certification were
      identified. MAIN OUTCOME MEASURE: ABMS member board certification. RESULTS: Of
      42,440 graduates in the study sample, 37,054 (87.3%) were board certified.
      Graduates in all specialty categories with first-attempt passing scores in the
      highest tertile (vs first-attempt failing scores) on US Medical Licensing
      Examination Step 2 Clinical Knowledge were more likely to be board certified;
      adjusted odds ratios (AORs) varied by specialty category, with the lowest odds
      for emergency medicine (87.4% vs 73.6%; AOR, 1.82; 95% CI, 1.03-3.20) and highest
      odds for radiology (98.1% vs 74.9%; AOR, 13.19; 95% CI, 5.55-31.32). In each
      specialty category except family medicine, graduates self-identified as
      underrepresented racial/ethnic minorities (vs white) were less likely to be board
      certified, ranging from 83.5% vs 95.6% in the pediatrics category (AOR, 0.44; 95%
      CI, 0.33-0.58) to 71.5% vs 83.7% in the other nongeneralist specialties category
      (AOR, 0.79; 95% CI, 0.64-0.96). With each $50,000 unit increase in debt (vs no
      debt), graduates choosing obstetrics/gynecology were less likely to be board
      certified (AOR, 0.89; 95% CI, 0.83-0.96), and graduates choosing family medicine
      were more likely to be board certified (AOR, 1.13; 95% CI, 1.01-1.26).
      CONCLUSION: Demographic and educational factors were associated with board
      certification among US medical school graduates in every specialty category
      examined; findings varied among specialty categories.

PMID- 21900137
TI  - Lesbian, gay, bisexual, and transgender-related content in undergraduate medical
      education.
AB  - CONTEXT: Lesbian, gay, bisexual, and transgender (LGBT) individuals experience
      health and health care disparities and have specific health care needs. Medical
      education organizations have called for LGBT-sensitive training, but how and to
      what extent schools educate students to deliver comprehensive LGBT patient care
      is unknown. OBJECTIVES: To characterize LGBT-related medical curricula and
      associated curricular development practices and to determine deans' assessments
      of their institutions' LGBT-related curricular content. DESIGN, SETTING, AND
      PARTICIPANTS: Deans of medical education (or equivalent) at 176 allopathic or
      osteopathic medical schools in Canada and the United States were surveyed to
      complete a 13-question, Web-based questionnaire between May 2009 and March 2010.
      MAIN OUTCOME MEASURE: Reported hours of LGBT-related curricular content. RESULTS:
      Of 176 schools, 150 (85.2%) responded, and 132 (75.0%) fully completed the
      questionnaire. The median reported time dedicated to teaching LGBT-related
      content in the entire curriculum was 5 hours (interquartile range [IQR], 3-8
      hours). Of the 132 respondents, 9 (6.8%; 95% CI, 2.5%-11.1%) reported 0 hours
      taught during preclinical years and 44 (33.3%; 95% CI, 25.3%-41.4%) reported 0
      hours during clinical years. Median US allopathic clinical hours were
      significantly different from US osteopathic clinical hours (2 hours [IQR, 0-4
      hours] vs 0 hours [IQR, 0-2 hours]; P = .008). Although 128 of the schools
      (97.0%; 95% CI, 94.0%-99.9%) taught students to ask patients if they "have sex
      with men, women, or both" when obtaining a sexual history, the reported teaching
      frequency of 16 LGBT-specific topic areas in the required curriculum was lower:
      at least 8 topics at 83 schools (62.9%; 95% CI, 54.6%-71.1%) and all topics at 11
      schools (8.3%; 95% CI, 3.6%-13.0%). The institutions' LGBT content was rated as
      "fair" at 58 schools (43.9%; 95% CI, 35.5%-52.4%). Suggested successful
      strategies to increase content included curricular material focusing on LGBT
      related health and health disparities at 77 schools (58.3%, 95% CI, 49.9%-66.7%)
      and faculty willing and able to teach LGBT-related curricular content at 67
      schools (50.8%, 95% CI, 42.2%-59.3%). CONCLUSION: The median reported time
      dedicated to LGBT-related topics in 2009-2010 was small across US and Canadian
      medical schools, but the quantity, content covered, and perceived quality of
      instruction varied substantially.

PMID- 21900138
TI  - Technology-enhanced simulation for health professions education: a systematic
      review and meta-analysis.
AB  - CONTEXT: Although technology-enhanced simulation has widespread appeal, its
      effectiveness remains uncertain. A comprehensive synthesis of evidence may inform
      the use of simulation in health professions education. OBJECTIVE: To summarize
      the outcomes of technology-enhanced simulation training for health professions
      learners in comparison with no intervention. DATA SOURCE: Systematic search of
      MEDLINE, EMBASE, CINAHL, ERIC, PsychINFO, Scopus, key journals, and previous
      review bibliographies through May 2011. STUDY SELECTION: Original research in any
      language evaluating simulation compared with no intervention for training
      practicing and student physicians, nurses, dentists, and other health care
      professionals. DATA EXTRACTION: Reviewers working in duplicate evaluated quality
      and abstracted information on learners, instructional design (curricular
      integration, distributing training over multiple days, feedback, mastery
      learning, and repetitive practice), and outcomes. We coded skills (performance in
      a test setting) separately for time, process, and product measures, and similarly
      classified patient care behaviors. DATA SYNTHESIS: From a pool of 10,903
      articles, we identified 609 eligible studies enrolling 35,226 trainees. Of these,
      137 were randomized studies, 67 were nonrandomized studies with 2 or more groups,
      and 405 used a single-group pretest-posttest design. We pooled effect sizes using
      random effects. Heterogeneity was large (I(2)>50%) in all main analyses. In
      comparison with no intervention, pooled effect sizes were 1.20 (95% CI, 1.04
      1.35) for knowledge outcomes (n = 118 studies), 1.14 (95% CI, 1.03-1.25) for time
      skills (n = 210), 1.09 (95% CI, 1.03-1.16) for process skills (n = 426), 1.18
      (95% CI, 0.98-1.37) for product skills (n = 54), 0.79 (95% CI, 0.47-1.10) for
      time behaviors (n = 20), 0.81 (95% CI, 0.66-0.96) for other behaviors (n = 50),
      and 0.50 (95% CI, 0.34-0.66) for direct effects on patients (n = 32). Subgroup
      analyses revealed no consistent statistically significant interactions between
      simulation training and instructional design features or study quality.
      CONCLUSION: In comparison with no intervention, technology-enhanced simulation
      training in health professions education is consistently associated with large
      effects for outcomes of knowledge, skills, and behaviors and moderate effects for
      patient-related outcomes.

PMID- 21900139
TI  - Genomics education for health care professionals in the 21st century.

PMID- 21900140
TI  - Conflict of interest disclosure in early education of medical students.

PMID- 21900141
TI  - The education and training of future physicians: why coaches can't be judges.

PMID- 21900142
TI  - Exploring unconscious bias in disparities research and medical education.

PMID- 21900143
TI  - Capturing curricula.

PMID- 21900144
TI  - Orchestrating excellence.

PMID- 21900146
TI  - Graduate medical education, 2010-2011.

PMID- 21900145
TI  - Medical schools in the United States, 2010-2011.

PMID- 21900147
TI  - JAMA patient page. Medical specialties.

PMID- 21900148
TI  - A randomized controlled trial investigating the effects of a low-glycemic index
      diet on pregnancy outcomes in gestational diabetes mellitus.
AB  - OBJECTIVE: The prevalence of gestational diabetes mellitus (GDM) is rising. There
      is little evidence to demonstrate the effectiveness of one dietary therapy over
      another. We aimed to investigate the effect of a low-glycemic index (LGI) versus
      a conventional high-fiber diet on pregnancy outcomes, neonatal anthropometry, and
      maternal metabolic profile in GDM. RESEARCH DESIGN AND METHODS: Ninety-nine women
      (age 26-42 years; mean +/- SD prepregnancy BMI 24 +/- 5 kg/m2) diagnosed with GDM
      at 20-32 weeks' gestation were randomized to follow either an LGI (n = 50; target
      glycemic index [GI] ~50) or a high-fiber moderate-GI diet (HF) (n = 49; target GI
      ~60). Dietary intake was assessed by 3-day food records. Pregnancy outcomes were
      collected from medical records. RESULTS: The LGI group achieved a modestly lower
      GI than the HF group (mean +/- SEM 47 +/- 1 vs. 53 +/- 1; P < 0.001). At birth,
      there was no significant difference in birth weight (LGI 3.3 +/- 0.1 kg vs. HF
      3.3 +/- 0.1 kg; P = 0.619), birth weight centile (LGI 52.5 +/- 4.3 vs. HF 52.2 +/
      4.0; P = 0.969), prevalence of macrosomia (LGI 2.1% vs. HF 6.7%; P = 0.157),
      insulin treatment (LGI 53% vs. HF 65%; P = 0.251), or adverse pregnancy outcomes.
      CONCLUSIONS: In intensively monitored women with GDM, an LGI diet and a
      conventional HF diet produce similar pregnancy outcomes.

PMID- 21900150
TI  - Transcriptional networks controlling adipocyte differentiation.
AB  - Adipocyte differentiation is regulated by a complex cascade of signals that drive
      the transcriptional reprogramming of the fibroblastic precursors. Genome-wide
      analyses of chromatin accessibility and binding of adipogenic transcription
      factors make it possible to generate "snapshots" of the transcription factor
      networks operating at specific time points during adipogenesis. Using such global
      "snapshots," we have demonstrated that dramatic remodeling of the chromatin
      template occurs within the first few hours following adipogenic stimulation and
      that many of the early transcription factors bind in a cooperative fashion to
      transcription factor hotspots. Such hotspots are likely to represent key
      chromatin nodes, where many adipogenic signaling pathways converge to drive the
      adipogenic transcriptional reprogramming.

PMID- 21900149
TI  - Circadian epigenomic remodeling and hepatic lipogenesis: lessons from HDAC3.
AB  - Circadian rhythms have evolved to anticipate metabolic needs across the 24-h
      light/dark cycle. This is accomplished by circadian expression of metabolic genes
      orchestrated by transcription factors through chromatin remodeling and histone
      modifications. Our recent genome-wide study on histone deacetylase 3 (HDAC3) in
      mouse liver provides novel insights into the molecular link between circadian
      rhythm and hepatic de novo lipogenesis. We found that liver-specific knockout of
      HDAC3 in adult mouse displays severe hepatic steatosis associated with enhanced
      de novo lipogenesis and increased expression of lipogenic genes. Genome-wide
      analysis (ChIP-seq) revealed a pronounced circadian pattern of HDAC3 occupancy on
      genes involved in lipid metabolism, which is inversely related to histone
      acetylation and RNA polymerase II recruitment at these sites. The cistromes of
      HDAC3 and its binding partner, nuclear receptor corepressor (NCoR), significantly
      overlap with that of Rev-erbalpha, a nuclear receptor directly involved in the
      core circadian machinery. Knockout of Rev-erbalpha in mouse also leads to hepatic
      steatosis and enhanced de novo lipogenesis. Collectively, these data suggest that
      the circadian epigenomic remodeling controlled by HDAC3, and largely directed by
      Rev-erbalpha, is essential for homeostasis of the lipogenic process in liver.

PMID- 21900151
TI  - On acetyl-CoA as a gauge of cellular metabolic state.
AB  - Many activities within a cell must be intimately coordinated with its metabolic
      state. Understanding these connections to metabolism is critical to deciphering
      the regulation of a variety of cellular processes. However, despite intensive
      research in these areas, the precise mechanisms by which a cell monitors its
      metabolic state remain controversial and poorly understood. Herein, we discuss
      the thesis that intracellular levels of the metabolite acetyl-CoA represent a
      critical gauge of cellular metabolic state, which is cleverly monitored by the
      cell through dynamic acetylation modifications to direct a variety of outputs
      connected to energy metabolism, cell growth, and survival.

PMID- 21900152
TI  - Mathematically modelling the spread of hepatitis C in injecting drug users.
AB  - Mathematical modelling can provide valuable insights into the biological and
      epidemiological properties of infectious diseases as well as the potential impact
      of intervention strategies employed by health organizations worldwide. In this
      paper, we develop a deterministic, compartmental mathematical model to
      approximate the spread of the hepatitis C virus (HCV) in an injecting drug user
      (IDU) population. Using analytical techniques, we find that the model behaviour
      is determined by the basic reproductive number R(0), where R(0) = 1 is a critical
      threshold separating two different outcomes. If R(0) <= 1 and HCV is initially
      present in the population, we find that the system will reach a disease-free
      equilibrium where HCV has been eliminated in all IDUs and needles. If R(0) > 1,
      then there is a unique positive endemic equilibrium which we show is locally
      stable. We then use simulations to verify our analytical results and examine the
      effect of different parameter values and intervention measures on HCV prevalence
      estimates.

PMID- 21900153
TI  - Building and searching tandem mass spectral libraries for peptide identification.
AB  - Spectral library searching is an emerging approach in peptide identifications
      from tandem mass spectra, a critical step in proteomic data analysis.
      Conceptually, the premise of this approach is that the tandem MS fragmentation
      pattern of a peptide under some fixed conditions is a reproducible fingerprint of
      that peptide, such that unknown spectra acquired under the same conditions can be
      identified by spectral matching. In actual practice, a spectral library is first
      meticulously compiled from a large collection of previously observed and
      identified tandem MS spectra, usually obtained from shotgun proteomics
      experiments of complex mixtures. Then, a query spectrum is then identified by
      spectral matching using recently developed spectral search engines. This review
      discusses the basic principles of the two pillars of this approach: spectral
      library construction, and spectral library searching. An overview of the software
      tools available for these two tasks, as well as a high-level description of the
      underlying algorithms, will be given. Finally, several new methods that utilize
      spectral libraries for peptide identification in ways other than straightforward
      spectral matching will also be described.

PMID- 21900155
TI  - The role of sphingolipids in respiratory disease.
AB  - Sphingolipids form a broad class of lipids with diverse functions ranging from
      membrane constituents to intracellular second messengers and extracellular
      mediators. They can be rapidly generated or converted into each other and they
      play pivotal roles in various cellular processes, many of which are broadly
      associated with inflammation and apoptosis. Among the numerous sphingolipids,
      ceramide and sphingosine-1-phosphate (S1P) have received the greatest attention.
      Ceramide is a hydrophobic molecule that is increased in the lungs of patients
      with cystic fibrosis and chronic obstructive pulmonary disease (COPD). Ceramide
      is the eponym for ceramide-rich membrane platforms. that need to form as a
      prerequisite to the uptake of several microorganisms including Pseudomonas
      aeruginosa, and as a prerequisite to many signaling processes including apoptosis
      and increased vascular permeability. Accordingly, abnormal amounts of enzymes
      involved in the synthesis of ceramide, such as neutral or acid sphingomyelinase,
      are found in emphysematic smokers and in patients with severe sepsis, and are
      considered as novel pharmacological targets. S1P acts as an extracellular
      mediator that opposes several actions of ceramide and acts by binding to G
      protein coupled S1P receptors (S1P(1)-S1P(5)). Of particular interest are S1P(1)
      receptors that enhance vascular barrier functions and are antiapoptotic.
      Therefore, S1P(1)-receptor ligands are suggested as novel drugs for COPD and
      acute lung injury. S1P is a potent chemotaxin for many leukocytes, it organizes
      lymphocyte trafficking and is involved in several key symptoms of asthma such as
      airway hyperresponsiveness and pulmonary eosinophil sequestration. S1P is formed
      by sphingosine kinases that have been identified as possible drug targets for the
      treatment of asthma. Based on these findings, several new drugs have recently
      been developed to specifically target sphingomyelinases, sphingosine kinases and
      S1P receptors for the treatment of COPD, cystic fibrosis, asthma and acute lung
      injury.

PMID- 21900154
TI  - Discovery and validation of serum protein changes in type 1 diabetes patients
      using high throughput two dimensional liquid chromatography-mass spectrometry and
      immunoassays.
AB  - Type 1 diabetes (T1D) is expected to cause significant changes in the serum
      proteome; however, few studies have systematically assessed the proteomic profile
      change associated with the disease. In this study, a semiquantitative spectral
      counting-based two dimensional liquid chromatography mass spectrometry platform
      was used to analyze serum samples from T1D patients and controls. In this
      discovery phase, significant differences were found for 21 serum proteins
      implicated in inflammation, oxidation, metabolic regulation, and autoimmunity. To
      assess the validity of these findings, six candidate proteins including
      adiponectin, insulin-like growth factor binding protein 2, serum amyloid protein
      A, C-reactive protein, myeloperoxidase, and transforming growth factor beta
      induced were selected for subsequent immune assays for 1139 T1D patients and 848
      controls. A series of statistical analyses using cases and controls matched for
      age, sex, and genetic risk confirmed that T1D patients have significantly higher
      serum levels for four of the six proteins: adiponectin (odds ratio (OR) = 1.95, p
      = 10(-27)), insulin-like growth factor binding protein 2 (OR = 2.02, p < 10(
      20)), C-reactive protein (OR = 1.13, p = 0.007), serum amyloid protein A (OR =
      1.51, p < 10(-16)); whereas the serum levels were significantly lower in patients
      than controls for the two other proteins: transforming growth factor beta induced
      (OR = 0.74, p < 10(-5)) and myeloperoxidase (OR = 0.51, p < 10(-41)). Compared
      with subjects in the bottom quartile, subjects in the top quartile for
      adiponectin (OR = 6.29, p < 10(-37)), insulin-like growth factor binding protein
      2 (OR = 7.95, p < 10(-46)), C-reactive protein (OR = 1.38, p = 0.025), serum
      amyloid protein A (OR = 3.36, p < 10(-16)) had the highest risk of T1D, whereas
      subjects in the top quartile of transforming growth factor beta induced (OR =
      0.41, p < 10(-11)) and myeloperoxidase (OR = 0.10, p < 10(-43)) had the lowest
      risk of T1D. These findings provided valuable information on the proteomic
      changes in the sera of T1D patients.

PMID- 21900156
TI  - Replication of the rotavirus genome requires an active ubiquitin-proteasome
      system.
AB  - Here we show that the ubiquitin-proteasome system is required for the efficient
      replication of rotavirus RRV in MA104 cells. The proteasome inhibitor MG132
      decreased the yield of infectious virus under conditions where it severely
      reduces the synthesis of not only viral but also cellular proteins. Addition of
      nonessential amino acids to the cell medium restored both viral protein synthesis
      and cellular protein synthesis, but the production of progeny viruses was still
      inhibited. In medium supplemented with nonessential amino acids, we showed that
      MG132 does not affect rotavirus entry but inhibits the replication of the viral
      genome. It was also shown that it prevents the efficient incorporation into
      viroplasms of viral polymerase VP1 and the capsid proteins VP2 and VP6, which
      could explain the inhibitory effect of MG132 on genome replication and infectious
      virus yield. We also showed that ubiquitination is relevant for rotavirus
      replication since the yield of rotavirus progeny in cells carrying a temperature
      sensitive mutation in the E1 ubiquitin-activating enzyme was reduced at the
      restrictive temperature. In addition, overexpression of ubiquitin in MG132
      treated MA104 cells partially reversed the effect of the inhibitor on virus
      yield. Altogether, these data suggest that the ubiquitin-proteasome (UP) system
      has a very complex interaction with the rotavirus life cycle, with both the
      ubiquitination and proteolytic activities of the system being relevant for virus
      replication.

PMID- 21900157
TI  - Cellular human CLE/C14orf166 protein interacts with influenza virus polymerase
      and is required for viral replication.
AB  - The influenza A virus polymerase associates with a number of cellular
      transcription-related factors, including RNA polymerase II. We previously
      described the interaction of influenza virus polymerase subunit PA with human
      CLE/C14orf166 protein (hCLE), a positive modulator of this cellular RNA
      polymerase. Here, we show that hCLE also interacts with the influenza virus
      polymerase complex and colocalizes with viral ribonucleoproteins. Silencing of
      hCLE causes reduction of viral polymerase activity, viral RNA transcription and
      replication, virus titer, and viral particle production. Altogether, these
      findings indicate that the cellular transcription factor hCLE is an important
      protein for influenza virus replication.

PMID- 21900158
TI  - Crystal structure of swine major histocompatibility complex class I SLA-1 0401
      and identification of 2009 pandemic swine-origin influenza A H1N1 virus cytotoxic
      T lymphocyte epitope peptides.
AB  - The presentation of viral epitopes to cytotoxic T lymphocytes (CTLs) by swine
      leukocyte antigen class I (SLA I) is crucial for swine immunity. To illustrate
      the structural basis of swine CTL epitope presentation, the first SLA crystal
      structures, SLA-1 0401, complexed with peptides derived from either 2009 pandemic
      H1N1 (pH1N1) swine-origin influenza A virus (S-OIV(NW9); NSDTVGWSW) or Ebola
      virus (Ebola(AY9); ATAAATEAY) were determined in this study. The overall peptide
      SLA-1 0401 structures resemble, as expected, the general conformations of other
      structure-solved peptide major histocompatibility complexes (pMHC). The major
      distinction of SLA-1 0401 is that Arg(156) has a "one-ballot veto" function in
      peptide binding, due to its flexible side chain. S-OIV(NW9) and Ebola(AY9) bind
      SLA-1 0401 with similar conformations but employ different water molecules to
      stabilize their binding. The side chain of P7 residues in both peptides is
      exposed, indicating that the epitopes are "featured" peptides presented by this
      SLA. Further analyses showed that SLA-1 0401 and human leukocyte antigen (HLA)
      class I HLA-A 0101 can present the same peptides, but in different conformations,
      demonstrating cross-species epitope presentation. CTL epitope peptides derived
      from 2009 pandemic S-OIV were screened and evaluated by the in vitro refolding
      method. Three peptides were identified as potential cross-species influenza virus
      (IV) CTL epitopes. The binding motif of SLA-1 0401 was proposed, and
      thermostabilities of key peptide-SLA-1 0401 complexes were analyzed by circular
      dichroism spectra. Our results not only provide the structural basis of peptide
      presentation by SLA I but also identify some IV CTL epitope peptides. These
      results will benefit both vaccine development and swine organ-based
      xenotransplantation.

PMID- 21900159
TI  - Structural studies of adeno-associated virus serotype 8 capsid transitions
      associated with endosomal trafficking.
AB  - The single-stranded DNA (ssDNA) parvoviruses enter host cells through receptor
      mediated endocytosis, and infection depends on processing in the early to late
      endosome as well as in the lysosome prior to nuclear entry for replication.
      However, the mechanisms of capsid endosomal processing, including the effects of
      low pH, are poorly understood. To gain insight into the structural transitions
      required for this essential step in infection, the crystal structures of empty
      and green fluorescent protein (GFP) gene-packaged adeno-associated virus serotype
      8 (AAV8) have been determined at pH values of 6.0, 5.5, and 4.0 and then at pH
      7.5 after incubation at pH 4.0, mimicking the conditions encountered during
      endocytic trafficking. While the capsid viral protein (VP) topologies of all the
      structures were similar, significant amino acid side chain conformational
      rearrangements were observed on (i) the interior surface of the capsid under the
      icosahedral 3-fold axis near ordered nucleic acid density that was lost
      concomitant with the conformational change as pH was reduced and (ii) the
      exterior capsid surface close to the icosahedral 2-fold depression. The 3-fold
      change is consistent with DNA release from an ordering interaction on the inside
      surface of the capsid at low pH values and suggests transitions that likely
      trigger the capsid for genome uncoating. The surface change results in disruption
      of VP-VP interface interactions and a decrease in buried surface area between VP
      monomers. This disruption points to capsid destabilization which may (i) release
      VP1 amino acids for its phospholipase A2 function for endosomal escape and
      nuclear localization signals for nuclear targeting and (ii) trigger genome
      uncoating.

PMID- 21900161
TI  - Detection and characterization of a distinct bornavirus lineage from healthy
      Canada geese (Branta canadensis).
AB  - Avian bornaviruses (ABV), identified in 2008, infect captive parrots and macaws
      worldwide. The natural reservoirs of these viruses are unknown. Reverse
      transcription-PCR (RT-PCR) was used to screen oropharyngeal/cloacal swab and
      brain samples from wild Canada geese (Branta canadensis) for ABV. Approximately
      2.9% of swab samples were positive for bornavirus sequences. Fifty-two percent of
      brain samples from 2 urban flocks also tested positive, and brain isolates were
      cultured in duck embryo fibroblasts. Phylogenetic analyses placed goose isolates
      in an independent cluster, and more notably, important regulatory sequences
      present in Borna disease virus but lacking in psittacine ABVs were present in
      goose isolates.

PMID- 21900160
TI  - Expression strategy of densonucleosis virus from the German cockroach, Blattella
      germanica.
AB  - Blattella germanica densovirus (BgDNV) is an autonomous parvovirus that infects
      the German cockroach. BgDNV possesses three mRNAs for NS proteins, two of which
      are splice variants of the unspliced transcript. The unspliced variant encodes
      open reading frame 5 (ORF5) (NS3), while NSspl1 encodes ORF3 (NS1) and ORF4 (NS2)
      and NSspl2 encodes the C-proximal half of NS1. BgDNV possesses three VP
      transcripts, one of which (VP) is unspliced, while the other two (VPspl1 and
      VPspl2) are generated by alternative splicing. The unspliced VP transcript
      contains both ORF1 and ORF2, while in VPspl1, ORF1 and ORF2 are joined in frame.
      The transcription of NS genes begins at an earlier stage of the virus life cycle
      than the transcription of VP genes. NS and VP transcripts overlap by 48
      nucleotides (nt). BgDNV is characterized by two additional NS transcripts
      overlapping by more than 1,650 nt with VP-coding transcripts. Four different
      bands (97, 85, 80, and 57 kDa) corresponding to three BgDNV capsid proteins were
      detected on SDS-PAGE. Mass spectrometry analysis showed that the amino acid
      composition of the 85-kDa and 80-kDa proteins is the same. Moreover, both of
      these proteins are ubiquitinated. The BgDNV PLA(2) domain, which is critical for
      cellular uptake of the virus, is located in ORF2 and is present only in VP1. In
      contrast to all of the parvoviruses studied in this respect, VP2 has a unique N
      terminus that is not contained within VP1 and VP3. In situ recognition with NS1-
      and VP-specific antibodies revealed an uneven pattern of NS1 expression
      resembling a halo within the nuclear membrane.

PMID- 21900162
TI  - RelA Ser276 phosphorylation-coupled Lys310 acetylation controls transcriptional
      elongation of inflammatory cytokines in respiratory syncytial virus infection.
AB  - Respiratory syncytial virus (RSV) is a negative-sense single-stranded RNA virus
      responsible for lower respiratory tract infections (LRTIs) in humans. In
      experimental models of RSV LRTI, the actions of the nuclear factor kappaB (NF
      kappaB) transcription factor mediate inflammation and pathology. We have shown
      that RSV replication induces a mitogen-and-stress-related kinase 1 (MSK-1)
      pathway that activates NF-kappaB RelA transcriptional activity by a process
      involving serine phosphorylation at serine (Ser) residue 276. In this study, we
      examined the mechanism by which phospho-Ser276 RelA mediates expression of the NF
      kappaB-dependent gene network. RelA-deficient mouse embryonic fibroblasts (MEFs)
      complemented with the RelA Ser276Ala mutant are deficient in CXCL2/Grobeta, KC,
      and interleukin-6 (IL-6) expression, but NFKBIA/IkappaBalpha is preserved. We
      show that RSV-induced RelA Ser276 phosphorylation is required for acetylation at
      Lys310, an event required for transcriptional activity and stable association of
      RelA with the activated positive transcriptional elongation factor (PTEF-b)
      complex proteins, bromodomain 4 (Brd4), and cyclin-dependent kinase 9 (CDK9). In
      contrast to gene loading pattern of PTEF-b proteins produced by tumor necrosis
      factor (TNF) stimulation, RSV induces their initial clearance followed by partial
      reaccumulation coincident with RelA recruitment. The RSV-induced binding patterns
      of the CDK9 substrate, phospho-Ser2 RNA polymerase (Pol) II, follows a similar
      pattern of clearance and downstream gene reaccumulation. The functional role of
      CDK9 was examined using CDK9 small interfering RNA (siRNA) and CDK inhibitors,
      where RSV-induced NF-kappaB-dependent gene expression was significantly
      inhibited. Finally, although RSV induces a transition from short transcripts to
      fully spliced mRNA in wild-type RelA (RelA WT)-expressing cells, this transition
      is not seen in cells expressing RelA Ser276Ala. We conclude that RelA Ser276
      phosphorylation mediates RelA acetylation, Brd4/CDK9 association, and activation
      of downstream inflammatory genes by transcriptional elongation in RSV infection.

PMID- 21900163
TI  - The fecal virome of pigs on a high-density farm.
AB  - Swine are an important source of proteins worldwide but are subject to frequent
      viral outbreaks and numerous infections capable of infecting humans. Modern
      farming conditions may also increase viral transmission and potential zoonotic
      spread. We describe here the metagenomics-derived virome in the feces of 24
      healthy and 12 diarrheic piglets on a high-density farm. An average of 4.2
      different mammalian viruses were shed by healthy piglets, reflecting a high level
      of asymptomatic infections. Diarrheic pigs shed an average of 5.4 different
      mammalian viruses. Ninety-nine percent of the viral sequences were related to the
      RNA virus families Picornaviridae, Astroviridae, Coronaviridae, and
      Caliciviridae, while 1% were related to the small DNA virus families
      Circoviridae, and Parvoviridae. Porcine RNA viruses identified, in order of
      decreasing number of sequence reads, consisted of kobuviruses, astroviruses,
      enteroviruses, sapoviruses, sapeloviruses, coronaviruses, bocaviruses, and
      teschoviruses. The near-full genomes of multiple novel species of porcine
      astroviruses and bocaviruses were generated and phylogenetically analyzed.
      Multiple small circular DNA genomes encoding replicase proteins plus two highly
      divergent members of the Picornavirales order were also characterized. The
      possible origin of these viral genomes from pig-infecting protozoans and
      nematodes, based on closest sequence similarities, is discussed. In summary, an
      unbiased survey of viruses in the feces of intensely farmed animals revealed
      frequent coinfections with a highly diverse set of viruses providing favorable
      conditions for viral recombination. Viral surveys of animals can readily document
      the circulation of known and new viruses, facilitating the detection of emerging
      viruses and prospective evaluation of their pathogenic and zoonotic potentials.

PMID- 21900164
TI  - Roles of the envelope proteins in the amplification of covalently closed circular
      DNA and completion of synthesis of the plus-strand DNA in hepatitis B virus.
AB  - Covalently closed circular DNA (cccDNA), the nuclear form of hepatitis B virus
      (HBV), is synthesized by repair of the relaxed circular (RC) DNA genome.
      Initially, cccDNA is derived from RC DNA from the infecting virion, but
      additional copies of cccDNA are derived from newly synthesized RC DNA molecules
      in a process termed intracellular amplification. It has been shown that the large
      viral envelope protein limits the intracellular amplification of cccDNA for duck
      hepatitis B virus. The role of the envelope proteins in regulating the
      amplification of cccDNA in HBV is not well characterized. The present report
      demonstrates regulation of synthesis of cccDNA by the envelope proteins of HBV.
      Ablation of expression of the envelope proteins led to an increase (>6-fold) in
      the level of cccDNA. Subsequent restoration of envelope protein expression led to
      a decrease (>50%) in the level of cccDNA, which inversely correlated with the
      level of the envelope proteins. We found that the expression of L protein alone
      or in combination with M and/or S proteins led to a decrease in cccDNA levels,
      indicating that L contributes to the regulation of cccDNA. Coexpression of L and
      M led to greater regulation than either L alone or L and S. Coexpression of all
      three envelope proteins was also found to limit completion of plus-strand DNA
      synthesis, and the degree of this effect correlated with the level of the
      proteins and virion secretion.

PMID- 21900165
TI  - HIV-1 coinfection and morphine coexposure severely dysregulate hepatitis C virus
      induced hepatic proinflammatory cytokine release and free radical production:
      increased pathogenesis coincides with uncoordinated host defenses.
AB  - Coinfection with human immunodeficiency virus type-1 (HIV-1) and hepatitis C
      virus (HCV) is a global problem that is more prevalent in injection drug users
      because they have a higher risk for acquiring both viruses. The roles of
      inflammatory cytokines and oxidative stress were examined in HIV-1- and HCV
      coinfected human hepatic cells. Morphine (the bioactive product of heroin), HIV-1
      Tat and the MN strain gp120 (gp120(MN)) proteins, and X4 HIV-1(LAI/IIIB) and R5
      HIV-1(SF162) isolates were used to study the mechanisms of disease progression in
      HCV (JFH1)-infected Huh7.5.1 cell populations. HCV increased tumor necrosis
      factor-alpha (TNF-alpha) and interleukin-6 (IL-6) release and augmented
      production of reactive oxygen species (ROS), nitric oxide (NO), and 3
      nitrotyrosine (3-NT) in Huh7.5.1 cells. Morphine preferentially affected R5
      tropic, but not X4-tropic, HIV-1 interactions with Huh7.5.1 cells. HIV-1 proteins
      or isolates increased cytokine release in HCV-infected cells, while adding
      morphine to coinfected cells caused complex imbalances, significantly disrupting
      cytokine secretion depending on the cytokine, morphine concentration, exposure
      duration, and particular pathogen involved. Production of ROS, NO, and 3-NT
      increased significantly in HCV- and HIV-1-coexposed cells while exposure to
      morphine further increased ROS. The proteasome inhibitor MG132 significantly
      decreased oxyradicals, cytokine levels, and HCV protein levels. Our findings
      indicate that hepatic inflammation is increased by combined exposure to HCV and
      HIV-1, that the ubiquitin-proteasome system and NF-kappaB contribute to key
      aspects of the response, and that morphine further exacerbates the disruption of
      host defenses. The results suggest that opioid abuse and HIV-1 coinfection each
      further accelerate HCV-mediated liver disease by dysregulating immune defenses.

PMID- 21900166
TI  - Transmission of clonal hepatitis C virus genomes reveals the dominant but
      transitory role of CD8+ T cells in early viral evolution.
AB  - The RNA genome of the hepatitis C virus (HCV) diversifies rapidly during the
      acute phase of infection, but the selective forces that drive this process remain
      poorly defined. Here we examined whether Darwinian selection pressure imposed by
      CD8(+) T cells is a dominant force driving early amino acid replacement in HCV
      viral populations. This question was addressed in two chimpanzees followed for 8
      to 10 years after infection with a well-defined inoculum composed of a clonal
      genotype 1a (isolate H77C) HCV genome. Detailed characterization of CD8(+) T cell
      responses combined with sequencing of recovered virus at frequent intervals
      revealed that most acute-phase nonsynonymous mutations were clustered in class I
      epitopes and appeared much earlier than those in the remainder of the HCV genome.
      Moreover, the ratio of nonsynonymous to synonymous mutations, a measure of
      positive selection pressure, was increased 50-fold in class I epitopes compared
      with the rest of the HCV genome. Finally, some mutation of the clonal H77C genome
      toward a genotype 1a consensus sequence considered most fit for replication was
      observed during the acute phase of infection, but the majority of these amino
      acid substitutions occurred slowly over several years of chronic infection.
      Together these observations indicate that during acute hepatitis C, virus
      evolution was driven primarily by positive selection pressure exerted by CD8(+) T
      cells. This influence of immune pressure on viral evolution appears to subside as
      chronic infection is established and genetic drift becomes the dominant
      evolutionary force.

PMID- 21900167
TI  - Annexin II binds to capsid protein VP1 of enterovirus 71 and enhances viral
      infectivity.
AB  - Enterovirus type 71 (EV71) causes hand, foot, and mouth disease (HFMD), which is
      mostly self-limited but may be complicated with a severe to fatal neurological
      syndrome in some children. Understanding the molecular basis of virus-host
      interactions might help clarify the largely unknown neuropathogenic mechanisms of
      EV71. In this study, we showed that human annexin II (Anx2) protein could bind to
      the EV71 virion via the capsid protein VP1. Either pretreatment of EV71 with
      soluble recombinant Anx2 or pretreatment of host cells with an anti-Anx2 antibody
      could result in reduced viral attachment to the cell surface and a reduction of
      the subsequent virus yield in vitro. HepG2 cells, which do not express Anx2,
      remained permissive to EV71 infection, though the virus yield was lower than that
      for a cognate lineage expressing Anx2. Stable transfection of plasmids expressing
      Anx2 protein into HepG2 cells (HepG2-Anx2 cells) could enhance EV71 infectivity,
      with an increased virus yield, especially at a low infective dose, and the
      enhanced infectivity could be reversed by pretreating HepG2-Anx2 cells with an
      anti-Anx2 antibody. The Anx2-interacting domain was mapped by yeast two-hybrid
      analysis to VP1 amino acids 40 to 100, a region different from the known receptor
      binding domain on the surface of the picornavirus virion. Our data suggest that
      binding of EV71 to Anx2 on the cell surface can enhance viral entry and
      infectivity, especially at a low infective dose.

PMID- 21900168
TI  - Histone H3 interacts and colocalizes with the nuclear shuttle protein and the
      movement protein of a geminivirus.
AB  - Geminiviruses are plant-infecting viruses with small circular single-stranded DNA
      genomes. These viruses utilize nuclear shuttle proteins (NSPs) and movement
      proteins (MPs) for trafficking of infectious DNA through the nuclear pore complex
      and plasmodesmata, respectively. Here, a biochemical approach was used to
      identify host factors interacting with the NSP and MP of the geminivirus Bean
      dwarf mosaic virus (BDMV). Based on these studies, we identified and
      characterized a host nucleoprotein, histone H3, which interacts with both the NSP
      and MP. The specific nature of the interaction of histone H3 with these viral
      proteins was established by gel overlay and in vitro and in vivo
      coimmunoprecipitation (co-IP) assays. The NSP and MP interaction domains were
      mapped to the N-terminal region of histone H3. These experiments also revealed a
      direct interaction between the BDMV NSP and MP, as well as interactions between
      histone H3 and the capsid proteins of various geminiviruses. Transient-expression
      assays revealed the colocalization of histone H3 and NSP in the nucleus and
      nucleolus and of histone H3 and MP in the cell periphery and plasmodesmata.
      Finally, using in vivo co-IP assays with a Myc-tagged histone H3, a complex
      composed of histone H3, NSP, MP, and viral DNA was recovered. Taken together,
      these findings implicate the host factor histone H3 in the process by which an
      infectious geminiviral DNA complex forms within the nucleus for export to the
      cell periphery and cell-to-cell movement through plasmodesmata.

PMID- 21900169
TI  - Human CD8+ and CD4+ T cell memory to lymphocytic choriomeningitis virus
      infection.
AB  - Although cellular immunity to acute lymphocytic choriomeningitis virus (LCMV)
      infection has been well characterized in experimental studies in mice, the T cell
      response to this virus in humans is incompletely understood. Thus, we analyzed
      the breadths, magnitudes, and differentiation phenotypes of memory LCMV-specific
      CD8(+) and CD4(+) T cells in three human donors displaying a variety of disease
      outcomes after accidental needle stick injury or exposure to LCMV. Although only
      a small cohort of donors was analyzed at a single time point postinfection,
      several interesting observations were made. First, we were able to detect LCMV
      specific CD8(+) and CD4(+) T cell responses directly ex vivo at 4 to 8 years
      after exposure, demonstrating the longevity of T cell memory in humans. Second,
      unlike in murine models of LCMV infection, we found that the breadths of memory
      CD8(+) and CD4(+) T cell responses were not significantly different from one
      another. Third, it seemed that the overall CD8(+) T cell response was augmented
      with increasing severity of disease, while the LCMV-specific CD4(+) T cell
      response magnitude was highly variable between the three different donors. Next,
      we found that LCMV-specific CD8(+) T cells in the three donors analyzed seemed to
      undergo an effector memory differentiation program distinct from that of CD4(+) T
      cells. Finally, the levels of expression of memory, costimulatory, and inhibitory
      receptors on CD8(+) and CD4(+) T cell subsets, in some instances, correlated with
      disease outcome. These data demonstrate for the first time LCMV-specific CD8(+)
      and CD4(+) T cells in infected humans and begin to provide new insights into
      memory T cell responses following an acute virus infection.

PMID- 21900170
TI  - Vaccine protection against simian immunodeficiency virus in monkeys using
      recombinant gamma-2 herpesvirus.
AB  - Recombinant strains of replication-competent rhesus monkey rhadinovirus (RRV)
      were constructed in which strong promoter/enhancer elements were used to drive
      expression of simian immunodeficiency virus (SIV) Env or Gag or a Rev-Tat-Nef
      fusion protein. Cultured rhesus monkey fibroblasts infected with each recombinant
      strain were shown to express the expected protein. Three RRV-negative and two RRV
      positive rhesus monkeys were inoculated intravenously with a mixture of these
      three recombinant RRVs. Expression of SIV Gag was readily detected in lymph node
      biopsy specimens taken at 3 weeks postimmunization. Impressive anti-SIV cellular
      immune responses were elicited on the basis of major histocompatibility complex
      (MHC) tetramer staining and gamma interferon enzyme-linked immunospot (ELISPOT)
      assays. Responses were much greater in magnitude in the monkeys that were
      initially RRV negative but were still readily detected in the two monkeys that
      were naturally infected with RRV at the time of immunization. By 3 weeks
      postimmunization, responses measured by MHC tetramer staining in the two Mamu
      A*01(+) RRV-negative monkeys reached 9.3% and 13.1% of all CD8(+) T cells in
      peripheral blood to the Gag CM9 epitope and 2.3% and 7.3% of all CD8(+) T cells
      in peripheral blood to the Tat SL8 epitope. Virus-specific CD8(+) T cell
      responses persisted at high levels up to the time of challenge at 18 weeks
      postimmunization, and responding cells maintained an effector memory phenotype.
      Despite the ability of the RRVenv recombinant to express high levels of Env in
      cultured cells, and despite the appearance of strong anti-RRV antibody responses
      in immunized monkeys, anti-Env antibody responses were below our ability to
      detect them. Immunized monkeys, together with three unimmunized controls, were
      challenged intravenously with 10 monkey infectious doses of SIVmac239. All five
      immunized monkeys and all three controls became infected with SIV, but peak viral
      loads were 1.2 to 3.0 log(10) units lower and chronic-phase viral loads were 1.0
      to 3.0 log(10) units lower in immunized animals than the geometric mean of
      unimmunized controls. These differences were statistically significant. Anti-Env
      antibody responses following challenge indicated an anamnestic response in the
      vaccinated monkeys. These findings further demonstrate the potential of
      recombinant herpesviruses as preventive vaccines for AIDS. We hypothesize that
      this live, replication-competent, persistent herpesvirus vector could match, or
      come close to matching, live attenuated strains of SIV in the degree of
      protection if the difficulty with elicitation of anti-Env antibody responses can
      be overcome.

PMID- 21900172
TI  - Human cytomegalovirus US7 is regulated synergistically by two virally encoded
      microRNAs and by two distinct mechanisms.
AB  - Human cytomegalovirus (HCMV) encodes at least 14 microRNAs (miRNAs) that act
      posttranscriptionally to repress gene expression. Although several HCMV miRNA
      targets of both cellular and viral origin have been identified, our knowledge of
      their function remains limited. HCMV miRNA targets, as well as phenotypes
      associated with HCMV miRNA mutants, have been difficult to identify since the
      downregulation of targets by a single miRNA is often less than 2-fold. Several
      factors can contribute to the strength of repression, including the mechanism of
      translational inhibition, the degree of complementarity between the miRNA and
      target mRNA, the number of binding sites for one miRNA, and cooperativity or
      antagonism between miRNAs. To determine the effect of multiple miRNAs on one
      gene, we examined the repression of a viral gene, US7. Here we demonstrate that
      the HCMV-encoded miRNAs miR-US5-1 and miR-US5-2 function in a highly synergistic
      manner to regulate US7, even at very low miRNA concentrations. Regulation of US7
      involves three functional miRNA binding sites: two that are completely
      complementary to the 3' untranslated region (3'UTR) and one that is imperfectly
      matched. Surprisingly, we observed equal contributions to inhibition from both
      complete and partially complementary sites, and repression was not completely
      abrogated until all three sites were mutated simultaneously. We also observed
      that the miRNA binding sites did not follow the spacing constraints for
      corepressive miRNAs observed in earlier reports. These results underscore the
      importance of evaluating the contribution of multiple miRNAs on gene regulation
      and shed new insight into miRNA:mRNA interactions.

PMID- 21900171
TI  - 2009 pandemic H1N1 influenza virus causes disease and upregulation of genes
      related to inflammatory and immune responses, cell death, and lipid metabolism in
      pigs.
AB  - There exists limited information about whether adaptation is needed for cross
      species transmission of the 2009 pandemic H1N1 influenza virus (pH1N1). Here, we
      compare the pathogenesis of two pH1N1 viruses, one derived from a human patient
      (A/CA/04/09 [CA09]) and the other from swine (A/swine/Alberta/25/2009 [Alb09]),
      with that of the 1918-like classical swine influenza virus (A/swine/Iowa/1930
      [IA30]) in the pig model. Both pH1N1 isolates induced clinical symptoms such as
      coughing, sneezing, decreased activity, fever, and labored breathing in
      challenged pigs, but IA30 virus did not cause any clinical symptoms except fever.
      Although both the pH1N1 viruses and the IA30 virus caused lung lesions, the pH1N1
      viruses were shed from the nasal cavities of challenged pigs whereas the IA30
      virus was not. Global gene expression analysis indicated that transcriptional
      responses of the viruses were distinct. pH1N1-infected pigs had an upregulation
      of genes related to inflammatory and immune responses at day 3 postinfection that
      was not seen in the IA30 infection, and expression levels of genes related to
      cell death and lipid metabolism at day 5 postinfection were markedly different
      from those of IA30 infection. These results indicate that both pH1N1 isolates are
      more virulent due in part to differences in the host transcriptional response
      during acute infection. Our study also indicates that pH1N1 does not need prior
      adaptation to infect pigs, has a high potential to be maintained in naive swine
      populations, and might reassort with currently circulating swine influenza
      viruses.

PMID- 21900173
TI  - Intragenic and extragenic suppression of a mutation in herpes simplex virus 1
      UL34 that affects both nuclear envelope targeting and membrane budding.
AB  - Late in infection herpesviruses move DNA-filled capsids from the nucleus to the
      cytoplasm by enveloping DNA-containing capsids at the inner nuclear membrane
      (INM) and deenveloping them at the outer nuclear membrane. This process requires
      two conserved herpesvirus proteins, pUL31 and pUL34. Interaction between pUL34
      and pUL31 is essential for targeting both proteins to the nuclear envelope (NE),
      and sequences that mediate the targeting interaction have been mapped in both
      proteins. Here, we show that a mutation in the INM-targeting domain of pUL34
      fails to support production of infectious virus or plaque formation. The mutation
      results in multiple defects, including impaired interaction between pUL34 and
      pUL31, poor NE targeting of pUL34, and misregulated, capsid-independent budding
      of the NE. The mutant defects in virus production, plaque formation, and pUL31
      interaction can be suppressed by other mutations in the INM-targeting domain of
      pUL31 and by additional mutations in the pUL34 coding sequence.

PMID- 21900174
TI  - The salt stress-induced LPA response in Chlamydomonas is produced via PLA2
      hydrolysis of DGK-generated phosphatidic acid.
AB  - The unicellular green alga Chlamydomonas has frequently been used as a eukaryotic
      model system to study intracellular phospholipid signaling pathways in response
      to environmental stresses. Earlier, we found that hypersalinity induced a rapid
      increase in the putative lipid second messenger, phosphatidic acid (PA), which
      was suggested to be generated via activation of a phospholipase D (PLD) pathway
      and the combined action of a phospholipase C/diacylglycerol kinase (PLC/DGK)
      pathway. Lysophosphatidic acid (LPA) was also increased and was suggested to
      reflect a phospholipase A2 (PLA2) activity based on pharmacological evidence. The
      question of PA's and LPA's origin is, however, more complicated, especially as
      both function as precursors in the biosynthesis of phospho- and galactolipids. To
      address this complexity, a combination of fatty acid-molecular species analysis
      and in vivo 32P-radiolabeling was performed. Evidence is provided that LPA is
      formed from a distinct pool of PA characterized by a high alpha-linolenic acid
      (18:3n-3) content. This molecular species was highly enriched in the
      polyphosphoinositide fraction, which is the substrate for PLC to form
      diacylglycerol. Together with differential 32P-radiolabeling studies and earlier
      PLD-transphosphatidylation and PLA2-inhibitor assays, the data were consistent
      with the hypothesis that the salt-induced LPA response is primarily generated
      through PLA2-mediated hydrolysis of DGK-generated PA and that PLD or de novo
      synthesis [via endoplasmic reticulum - or plastid-localized routes] is not a
      major contributor.

PMID- 21900175
TI  - Cubbing in proapolipoprotein maturation.

PMID- 21900176
TI  - Primary vascularization of the graft determines the immunodominance of murine
      minor H antigens during organ transplantation.
AB  - Grafts can be rejected even when matched for MHC because of differences in the
      minor histocompatibility Ags (mH-Ags). H4- and H60-derived epitopes are known as
      immunodominant mH-Ags in H2(b)-compatible BALB.B to C57BL/6 transplantation
      settings. Although multiple explanations have been provided to explain
      immunodominance of Ags, the role of vascularization of the graft is yet to be
      determined. In this study, we used heart (vascularized) and skin
      (nonvascularized) transplantations to determine the role of primary
      vascularization of the graft. A higher IFN-gamma response toward H60 peptide
      occurs in heart recipients. In contrast, a higher IFN-gamma response was
      generated against H4 peptide in skin transplant recipients. Peptide-loaded
      tetramer staining revealed a distinct antigenic hierarchy between heart and skin
      transplantation: H60-specific CD8(+) T cells were the most abundant after heart
      transplantation, whereas H4-specific CD8(+) T cells were more abundant after skin
      graft. Neither the tissue-specific distribution of mH-Ags nor the draining lymph
      node-derived dendritic cells correlated with the observed immunodominance.
      Interestingly, non-primarily vascularized cardiac allografts mimicked skin grafts
      in the observed immunodominance, and H60 immunodominance was observed in
      primarily vascularized skin grafts. However, T cell depletion from the BALB.B
      donor prior to cardiac allograft induces H4 immunodominance in vascularized
      cardiac allograft. Collectively, our data suggest that immediate transmigration
      of donor T cells via primary vascularization is responsible for the
      immunodominance of H60 mH-Ag in organ and tissue transplantation.

PMID- 21900177
TI  - Immunotherapy with costimulatory dendritic cells to control autoimmune
      inflammation.
AB  - Costimulation-deficient dendritic cells (DCs) prevent autoimmune disease in mouse
      models. However, autoimmune-prone mice and humans fail to control expansion of
      peripheral autoreactive effector memory T cells (T(EMs)), which resist
      immunoregulation by costimulation-deficient DCs. In contrast, activation of DC
      costimulation may be coupled with regulatory capacity. To test whether
      costimulatory DCs control T(EMs) and attenuate established autoimmune disease, we
      used RelB-deficient mice, which have multiorgan inflammation, expanded peripheral
      autoreactive T(EMs), and dysfunctional Foxp3(+) regulatory T cells (Tregs) cells
      and conventional DCs. T(EMs) were regulated by Foxp3(+) Tregs when costimulated
      by CD3/CD28-coated beads or wild-type DCs but not DCs deficient in RelB or
      CD80/CD86. After transfer, RelB and CD80/CD86-sufficient DCs restored tolerance
      and achieved a long-term cure of autoimmune disease through costimulation of
      T(EM) and Foxp3(+) Treg IFN-gamma production, as well as induction of IDO by host
      APCs. IDO was required for regulation of T(EMs) and suppression of organ
      inflammation. Our data challenge the paradigm that costimulation-deficient DCs
      are required to regulate established autoimmune disease to avoid T(EM) activation
      and demonstrate cooperative cross-talk between costimulatory DCs, IFN-gamma, and
      IDO-dependent immune regulation. IFN-gamma and IDO activity may be good surrogate
      biomarkers measured against clinical efficacy in trials of autoimmune disease
      immunoregulation.

PMID- 21900178
TI  - Pathogenic nematodes suppress humoral responses to third-party antigens in vivo
      by IL-10-mediated interference with Th cell function.
AB  - One third of the human population is infected with helminth parasites. To promote
      their longevity and to limit pathology, helminths have developed several
      strategies to suppress the immune response of their host. As this immune
      suppression also acts on unrelated third-party Ags, a preexisting helminth
      infection may interfere with vaccination efficacy. In this study, we show that
      natural infection with Litomosoides sigmodontis suppressed the humoral response
      to thymus-dependent but not to thymus-independent model Ags in C57BL/6 mice.
      Thereby, we provide evidence that reduced humoral responses were mediated by
      interference with Th cell function rather than by direct suppression of B cells
      in L. sigmodontis-infected mice. We directly demonstrate suppression of Ag
      specific proliferation in OVA-specific Th cells after adoptive transfer into L.
      sigmodontis-infected mice that led to equally reduced production of OVA-specific
      IgG. Transferred Th cells displayed increased frequencies of Foxp3(+) after in
      vivo stimulation within infected but not within naive mice. Helminth-mediated
      suppression was induced by established L. sigmodontis infections but was
      completely independent of the individual worm burden. Using DEREG mice, we rule
      out a central role for host-derived regulatory T cells in the suppression of
      transferred Th cell proliferation. In contrast, we show that L. sigmodontis
      induced, host-derived IL-10 mediated Foxp3 induction in transferred Th cells and
      significantly contributed to the observed Th cell hypoproliferation within
      infected mice.

PMID- 21900179
TI  - Myeloid-specific expression of human lysosomal acid lipase corrects malformation
      and malfunction of myeloid-derived suppressor cells in lal-/- mice.
AB  - Lysosomal acid lipase (LAL) cleaves cholesteryl esters and triglycerides to
      generate free fatty acids and cholesterol in lysosomes. LAL deficiency causes
      expansion of CD11b(+)Gr-1(+) immature myeloid cells, loss of T cells, and
      impairment of T cell function. To test how myeloid cell LAL controls myelopoiesis
      and lymphopoiesis, a myeloid-specific doxycycline-inducible transgenic system was
      used to reintroduce human lysosomal acid lipase (hLAL) expression into LAL gene
      knockout (lal(-/-)) mice. Expression of hLAL in myeloid cells of lal(-/-) mice
      reversed abnormal myelopoiesis in the bone marrow starting at the granulocyte
      monocyte progenitor stage and reduced systemic expansion of myeloid-derived
      suppressor cells (MDSCs). Myeloid hLAL expression inhibited reactive oxygen
      species production and arginase expression in CD11b(+)Gr-1(+) cells of lal(-/-)
      mice. Structural organization of the thymus and spleen was partially restored in
      association with reduced infiltration of CD11b(+)Gr-1(+) cells in these mice. In
      the thymus, reconstitution of myeloid cell LAL restored development of thymocytes
      at the double-negative DN3 stage. Myeloid cell LAL expression improved the
      proliferation and function of peripheral T cells. In vitro coculture experiments
      showed that myeloid hLAL expression in lal(-/-) mice reversed CD11b(+)Gr-1(+)
      myeloid cell suppression of CD4(+) T cell proliferation, T cell signaling
      activation, and lymphokine secretion. Blocking stat3 and NF-kappaB p65 signaling
      by small-molecule inhibitors in MDSCs achieved a similar effect. Injection of
      anti-Gr-1 Ab into lal(-/-) mice to deplete MDSCs restored T cell proliferation.
      These studies demonstrate that LAL in myeloid cells plays a critical role in
      maintaining normal hematopoietic cell development and balancing immunosuppression
      and inflammation.

PMID- 21900181
TI  - A live imaging cell motility screen identifies prostaglandin E2 as a T cell stop
      signal antagonist.
AB  - The T cell migration stop signal is a central step in T cell activation and
      inflammation; however, its regulatory mechanisms remain largely unknown. Using a
      live-cell, imaging-based, high-throughput screen, we identified the PG, PGE(2),
      as a T cell stop signal antagonist. Src kinase inhibitors, microtubule
      inhibitors, and PGE(2) prevented the T cell stop signal, and impaired T cell-APC
      conjugation and T cell proliferation induced by primary human allogeneic
      dendritic cells. However, Src inhibition, but not PGE(2) or microtubule
      inhibition, impaired TCR-induced ZAP-70 signaling, demonstrating that T cell stop
      signal antagonists can function either upstream or downstream of proximal TCR
      signaling. Moreover, we found that PGE(2) abrogated TCR-induced activation of the
      small GTPase Rap1, suggesting that PGE(2) may modulate T cell adhesion and
      stopping through Rap1. These results identify a novel role for PGs in preventing
      T cell stop signals and limiting T cell activation induced by dendritic cells.

PMID- 21900180
TI  - Impaired B cell development and function in the absence of IkappaBNS.
AB  - IkappaBNS has been identified as a member of the IkappaB family of NF-kappaB
      inhibitors, which undergoes induction upon TCR signaling. Mice carrying a
      targeted gene disruption of IkappaBNS demonstrate dysregulation of cytokines in T
      cells, macrophages, and dendritic cells. IkappaBNS mediates both positive and
      negative gene regulation, depending on individual cell type and/or cytokine. In
      this study, we demonstrate an additional role for IkappaBNS in the B cell
      lineage. B cells from IkappaBNS knockout (KO) mice were impaired in proliferative
      responses to LPS and anti-CD40. IgM and IgG3 Igs were drastically reduced in the
      serum of IkappaBNS KO mice, although IkappaBNS KO B cells exhibited a higher
      level of surface IgM than that found in wild-type mice. Switching to IgG3 was
      significantly reduced in IkappaBNS KO B cells. The in vitro induction of plasma
      cell development demonstrated that progression to Ab-secreting cells was impaired
      in IkappaBNS KO B cells. In agreement with this finding, the number of Ab
      secreting cells in the spleens of IkappaBNS KO mice was reduced and production of
      Ag-specific Igs was lower in IkappaBNS KO mice after influenza infection as
      compared with wild-type mice. Additionally, IkappaBNS KO mice lacked B1 B cells
      and exhibited a reduction in marginal zone B cells. Thus, IkappaBNS significantly
      impacts the development and functions of B cells and plasma cells.

PMID- 21900182
TI  - Intestinal epithelial cells modulate CD4 T cell responses via the thymus leukemia
      antigen.
AB  - The intestinal epithelium is comprised of a monolayer of intestinal epithelial
      cells (IEC), which provide, among other functions, a physical barrier between the
      high Ag content of the intestinal lumen and the sterile environment beyond the
      epithelium. IEC express a nonclassical MHC class I molecule known as the thymus
      leukemia (TL) Ag. TL is known to interact with CD8alphaalpha-expressing cells,
      which are abundant in the intestinal intraepithelial lymphocyte compartment. In
      this report, we provide evidence indicating that expression of TL by IEC
      modulates the cytokine profile of CD4(+) T cells favoring IL-17 production. We
      show in an adoptive transfer model of colitis that donor-derived cells become
      more pathogenic when TL is expressed on IEC in recipient animals. Moreover,
      TL(+)IEC promote development of IL-17-mediated responses capable of protecting
      mice from Citrobacter rodentium infection. We also show that modulation of IL-17
      mediated responses by TL(+)IEC is controlled by the expression of CD8alpha on
      CD4(+) T cells. Overall, our results provide evidence for an important
      interaction between IEC and CD4(+) T cells via TL, which modulates mucosal immune
      responses.

PMID- 21900184
TI  - Retraction: Stimulation of FcgammaRI on primary sensory neurons increases insulin
      like growth factor-I production, thereby reducing reperfusion-induced renal
      injury in mice.

PMID- 21900183
TI  - The BTB-ZF family of transcription factors: key regulators of lineage commitment
      and effector function development in the immune system.
AB  - Successful immunity depends upon the activity of multiple cell types. Commitment
      of pluripotent precursor cells to specific lineages, such as T or B cells, is
      obviously fundamental to this process. However, it is also becoming clear that
      continued differentiation and specialization of lymphoid cells is equally
      important for immune system integrity. Several members of the BTB-ZF family have
      emerged as critical factors that control development of specific lineages and
      also of specific effector subsets within these lineages. For example, BTB-ZF
      genes have been shown to control T cell versus B cell commitment and CD4 versus
      CD8 lineage commitment. Others, such as PLZF for NKT cells and Bcl-6 for T
      follicular helper cells, are necessary for the acquisition of effector functions.
      In this review, we summarize current findings concerning the BTB-ZF family
      members with a reported role in the immune system.

PMID- 21900185
TI  - Impact of serial troponin release on outcomes in patients with acute heart
      failure: analysis from the PROTECT pilot study.
AB  - BACKGROUND: Cardiac troponin T (cTnT) elevation is common and is a predictor of
      outcomes in patients with acute heart failure (AHF). The degree and progression
      of cTnT release during hospitalization of patients with AHF is unclear. We
      evaluated the incidence of cTnT release during AHF hospitalization and the
      relationship of cTnT release with outcomes. METHODS AND RESULTS: The Placebo
      controlled Randomized study of the selective A(1) adenosine receptor antagonist
      rolofylline for patients hospitalized with acute heart failure and volume
      Overload to assess Treatment Effect on Congestion and renal funcTion (PROTECT)
      pilot study was a multicenter, double-blind study of patients with AHF.
      Measurements of cTnT were collected at randomization and days 2, 3, 4, and 7.
      Patients were classified on the basis of their serum cTnT levels at baseline:
      positive (>0.03 ng/mL), detectable (>0.01 ng/mL), and negative (<=0.01 ng/mL). A
      detectable cTnT level developed during the study (after baseline) was classified
      as cTnT conversion: 288 patients were included; 172 (60%) patients had detectable
      cTnT levels and 97 (34%) had positive values (>0.03 ng/mL) at baseline. Of the
      116 patients with negative troponin at baseline, 24 (21%) had elevated cTnT
      levels by day 7. On multivariable analysis, positive cTnT at baseline was an
      independent predictor of the composite end point of cardiovascular/renal
      rehospitalization or death at 60 days (hazard ratio, 1.84; 95% confidence
      interval, 1.04-3.26; P=0.036). Kaplan-Meier curves showed similar worse outcomes
      in patients with troponin conversion and positive troponin at baseline.
      CONCLUSIONS: There was a high prevalence of baseline cTnT elevation in this
      cohort; 21% of those negative at baseline converted to detectable levels by day
      7. Positive troponin at baseline, and conversion to positive levels, were
      associated with worse outcomes at 60 days. Clinical Trial Registration- URL:
      http://www.clinicaltrials.gov. Unique identifiers: NCT00328692 and NCT00354458.

PMID- 21900187
TI  - Feasibility of a heart failure disease management program in eastern Europe:
      Tbilisi, Georgia.
AB  - BACKGROUND: Little is known about the importation of a heart failure disease
      management program (HFDMP) into low- and middle-income countries. We examined the
      feasibility of importing a HFDMP into the country of Georgia, located in the
      Caucuses. METHODS AND RESULTS: Patients with ejection fraction <=40% were
      enrolled into a prospective, observational study consisting of a new HFDMP
      staffed by local cardiologists. Medications, emergency department use, hospital
      admissions, and mortality were assessed by interviews with patients or their
      families. Screening resulted in 400 patients who were followed for 10.2+/-3.5
      months. beta-Blocker prescriptions increased from 7.4-80.7% (P<0.001),
      angiotensin-converting enzyme inhibitor prescriptions increased from 18.4-92.6%
      (P<0.001), and mean systolic blood pressure declined from 145 to 114 mm Hg
      (P<0.001). Patients visiting the emergency department and hospitalizations were
      lowered by 40.7% and 52.5%, respectively, but were also influenced by the
      outbreak of war, during which 17.5% (n=70) of patients received follow-up in
      refugee tents. All-cause mortality extended to 7% of patients, with 12 of 28
      deaths caused by war-related events. CONCLUSIONS: Importation of a Western HFDMP
      was demonstrated to be feasible, with a 5-fold increase in the use of recommended
      therapies, reduction of blood pressure, decrease of emergency department visits,
      and hospitalizations for heart failure. These measures could result in
      substantial cost savings in resource-limited settings, but assessment is
      complicated in unstable areas. Translating effective interventions to low- and
      middle-income countries requires sensitivity to regional cultures and flexibility
      to adapt both clinical goals and strategies to unexpected conditions.

PMID- 21900186
TI  - The relationship between serum markers of collagen turnover and cardiovascular
      outcome in the elderly: the Cardiovascular Health Study.
AB  - BACKGROUND: The deposition of collagen fibrils in the myocardial extracellular
      matrix increases with age and plays a key role in the pathophysiology of heart
      failure (HF). We sought to determine the predictive value of serum markers of
      collagen turnover for incident HF and cardiovascular (CV) morbidity, mortality,
      and all-cause mortality in elderly individuals. METHODS AND RESULTS: In 880
      participants in the Cardiovascular Health Study (mean age, 77+/-6 years; 48%
      women), serum levels of carboxyl-terminal peptide of procollagen type I (PIP),
      carboxyl-terminal telopeptide of collagen type I (CITP), and amino-terminal
      peptide of procollagen type III (PIIINP) were measured in 4 groups: HF with
      reduced ejection fraction (HFREF; n=146, EF <55%); HF with preserved EF (HFPEF;
      n=175, EF >=55%), control subjects with CV risk factors but not HF (CVD; n=280),
      and healthy control subjects free of CV disease (n=279). Relationships between
      these serum markers and outcome at follow-up of 12+/-4 years (range, 3-17 years)
      was determined in six models including those adjusted for conventional risk
      factors, renal function, NT-proBNP and agents which interfere with collagen
      synthesis. For the entire cohort, in unadjusted and adjusted models, both PIIINP
      and CITP were associated with myocardial infarction, incident HF, hospitalization
      for HF, cardiovascular and all-cause mortality. In healthy control subjects, CITP
      and PIIINP were associated with all-cause death. In control subjects with risk
      factors, CITP was associated with incident HF, and in participants with HFPEF,
      CITP was associated with hospitalization for HF. No collagen biomarker was
      associated with outcome in participants with HFREF, and PIP was not associated
      with outcome in the cohort or its subgroups. CONCLUSIONS: In both healthy and
      elderly individuals with CV disease at risk of developing HF, CITP and PIIINP are
      significantly associated with multiple adverse cardiac outcomes including
      myocardial infarction, HF, and death. Clinical Trial Registration- URL:
      http://www.clinicaltrials.gov. Unique identifier: NCT00005133.

PMID- 21900188
TI  - Right ventricular failure in idiopathic pulmonary arterial hypertension is
      associated with inefficient myocardial oxygen utilization.
AB  - BACKGROUND: In idiopathic pulmonary arterial hypertension (IPAH), increased right
      ventricular (RV) power is required to maintain cardiac output. For this, RV O2
      consumption (MVO2) must increase by augmentation of O2 supply and/or improvement
      of mechanical efficiency-ratio of power output to MVO2. In IPAH with overt RV
      failure, however, there is evidence that O2 supply (perfusion) reserve is
      reduced, leaving only increase in either O2 extraction or mechanical efficiency
      as compensatory mechanisms. We related RV mechanical efficiency to clinical and
      hemodynamic parameters of RV function in patients with IPAH and associated it
      with glucose metabolism. METHODS AND RESULTS: The patients included were in New
      York Heart Association (NYHA) class II (n=8) and class III (n=8). They underwent
      right heart catheterization, MRI, and H2(15)O-, (15)O2-, C(15)O-, and 18FDG-PET.
      RV power and O2 supply were similar in both groups (NYHA class II versus class
      III: 0.54+/-0.14 versus 0.47+/-0.12 J/s and 0.109+/-0.022 versus 0.128+/-0.026 mL
      O2/min per gram, respectively). RV O2 extraction was near-significantly lower in
      NYHA class II compared with NYHA class III (63+/-17% versus 75+/-16%,
      respectively, P=0.10). As a result, MVO2 was significantly lower (0.066+/-0.012
      versus 0.092+/-0.010 mL O2/min per gram, respectively, P=0.006). RV efficiency
      was reduced in NYHA class III (13.9+/-3.8%) compared with NYHA class II (27.8+/
      7.6%, P=0.001). Septal bowing, measured by MRI, correlated with RV efficiency (r
      = -0.59, P=0.020). No relation was found between RV efficiency and glucose uptake
      rate. RV mechanical efficiency and ejection fraction were closely related
      (r=0.81, P<0.001). CONCLUSIONS: RV failure in IPAH was associated with reduced
      mechanical efficiency that was partially explained by RV mechanical dysfunction
      but not by a metabolic shift.

PMID- 21900189
TI  - Prognostic relevance of 18-F FDG PET/CT in newly diagnosed multiple myeloma
      patients treated with up-front autologous transplantation.
AB  - We prospectively analyzed the prognostic relevance of positron emission
      tomography-computed tomography (PET/CT) at diagnosis, after thalidomide
      dexamethasone (TD) induction therapy and double autotransplantation (ASCT) in 192
      newly diagnosed multiple myeloma (MM) patients. Presence at baseline of at least
      3 focal lesions (FLs; 44% of cases), a standardized uptake value (SUV) > 4.2
      (46%), and extramedullary disease (EMD; 6%) adversely affected 4-year estimates
      of progression-free survival (PFS; >= 3 FLs: 50%; SUV > 4.2: 43%; presence of
      EMD: 28%). SUV > 4.2 and EMD were also correlated with shorter overall survival
      (OS; 4-year rates: 77% and 66%, respectively). Persistence of SUV > 4.2 after TD
      induction was an early predictor for shorter PFS. Three months after ASCT, PET/CT
      was negative in 65% of patients whose 4-year rates of PFS and OS were superior to
      those of PET-positive patients (PFS: 66% and OS: 89%). In a multivariate
      analysis, both EMD and SUV > 4.2 at baseline and persistence of
      fluorodeoxyglucose (FDG) uptake after ASCT were independent variables adversely
      affecting PFS. PET/CT involvement at diagnosis, after novel agent-based induction
      and subsequent ASCT is a reliable predictor of prognosis in MM patients. This
      study is registered at www.clinicaltrials.gov as NTC01341262.

PMID- 21900190
TI  - Inhibition of IL-32 activation by alpha-1 antitrypsin suppresses alloreactivity
      and increases survival in an allogeneic murine marrow transplantation model.
AB  - Interleukin (IL)-32 was originally identified in natural killer cells and IL-2
      activated human T lymphocytes. As T cells are activated in allogeneic
      transplantation, we determined the role of IL-32 in human mixed lymphocyte
      cultures (MLCs) and GVHD. In allogeneic MLCs, IL-32 increased two-fold in
      responding T cells, accompanied by five-fold increases of TNFalpha, IL-6, and IL
      8. After allogeneic hematopoietic cell transplantation, IL-32 mRNA levels in
      blood leukocytes were statistically significantly higher in patients with acute
      GVHD (n = 10) than in serial samples from patients who did not develop acute GVHD
      (n = 5; P = .02). No significant changes in IL-32 levels were present in patients
      with treated (n = 14) or untreated (n = 8) chronic GVHD, compared with healthy
      controls (n = 8; P = .5, and P = .74, respectively). As IL-32 is activated by
      proteinase-3 (PR3), we determined the effect of the serine protease inhibitor
      alpha-1 antitrypsin (AAT) on IL-32 levels and showed suppression of IL-32 and T
      lymphocyte proliferation in MLCs. In an MHC-minor antigen disparate murine
      transplant model, preconditioning and postconditioning treatment with AAT
      resulted in attenuation or prevention of GVHD and superior survival compared with
      albumin-treated controls (80% vs 44%; P = .04). These findings suggest that AAT
      modulates immune and inflammatory functions and may represent a novel approach to
      prevent or treat GVHD.

PMID- 21900191
TI  - Pivotal trial with plant cell-expressed recombinant glucocerebrosidase,
      taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease.
AB  - Taliglucerase alfa (Protalix Biotherapeutics, Carmiel, Israel) is a novel plant
      cell-derived recombinant human beta-glucocerebrosidase for Gaucher disease. A
      phase 3, double-blind, randomized, parallel-group, comparison-dose (30 vs 60 U/kg
      body weight/infusion) multinational clinical trial was undertaken. Institutional
      review board approvals were received. A 9-month, 20-infusion trial used
      inclusion/exclusion criteria in treatment-naive adult patients with splenomegaly
      and thrombocytopenia. Safety end points were drug-related adverse events: Ab
      formation and hypersensitivity reactions. Primary efficacy end point was
      reduction in splenic volume measured by magnetic resonance imaging. Secondary end
      points were: changes in hemoglobin, hepatic volume, and platelet counts.
      Exploratory parameters included biomarkers and bone imaging. Twenty-nine patients
      (11 centers) completed the protocol. There were no serious adverse events; drug
      related adverse events were mild/moderate and transient. Two patients (6%)
      developed non-neutralizing IgG Abs; 2 other patients (6%) developed
      hypersensitivity reactions. Statistically significant spleen reduction was
      achieved at 9 months: 26.9% (95% confidence interval [CI]: -31.9, -21.8) in the
      30-unit dose group and 38.0% (95% CI: -43.4, -32.8) in the 60-unit dose group
      (both P < .0001); and in all secondary efficacy end point measures, except
      platelet counts at the lower dose. These results support safety and efficacy of
      taliglucerase alfa for Gaucher disease.

PMID- 21900192
TI  - Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: long-term results of
      the HLH-94 treatment protocol.
AB  - Hemophagocytic lymphohistiocytosis (HLH) used to have a dismal prognosis. We
      report the final results of HLH-94, the largest prospective
      diagnostic/therapeutic HLH study so far. The treatment includes immunosuppressive
      and cytotoxic therapy aiming at clinical remission, followed by HSCT in patients
      with familial, persistent, or recurrent disease. Altogether, 249 patients
      fulfilled inclusion criteria and started HLH-94 therapy (July 1994-December
      2003); 227 (91%) were followed-up for >= 5 years. At 6.2 years median follow-up,
      estimated 5-year probability of survival was 54% +/- 6%. Seventy-two patients
      (29%) died before HSCT, 64 within 1 year, 97% of whom had active disease. In 124
      patients who underwent HSCT, 5-year survival was 66 +/- 8%; tendency to increased
      survival (P = .064) in patients with nonactive disease at HSCT. Patients with
      familial disease had a 5-year survival of 50% +/- 13%; none survived without
      HSCT. Patients deceased during the first 2 months more often had jaundice, edema,
      and elevated creatinine. Forty-nine patients (20%) were alive without signs of
      HLH activity and off-therapy > 1-year without HSCT; they presented at older age
      (P < .001), were more often female (P = .011), and less often had CNS disease (P
      < .001) or hepatomegaly (P = .007). To conclude, HLH-94 chemoimmunotherapy has
      considerably improved outcome in HLH. Collaborative efforts are needed to further
      reduce early mortality, HSCT-related mortality, and neurologic late effects.

PMID- 21900193
TI  - Outcome according to cytogenetic abnormalities and DNA ploidy in myeloma patients
      receiving short induction with weekly bortezomib followed by maintenance.
AB  - Cytogenetic abnormalities (CAs) such as t(4;14), t(14;16) or del(17p), and
      nonhyperdiploidy are associated with poor prognosis in multiple myeloma. We
      evaluated the influence of CAs by FISH and DNA ploidy by flow cytometry on
      response and survival in 232 elderly, newly diagnosed multiple myeloma patients
      receiving an induction with weekly bortezomib followed by maintenance therapy
      with bortezomib-based combinations. Response was similar in the high-risk and
      standard-risk CA groups, both after induction (21% vs 27% complete responses
      [CRs]) and maintenance (39% vs 45% CR). However, high-risk patients showed
      shorter progression-free survival (PFS) than standard-risk patients, both from
      the first (24 vs 33 months; P = .04) and second randomization (17 vs 27 months; P
      = .01). This also translated into shorter overall survival (OS) for high-risk
      patients (3-year OS: 55% vs 77%; P = .001). This adverse prognosis applied to
      either t(4;14) or del(17p). Concerning DNA ploidy, hyperdiploid patients showed
      longer OS than nonhyperdiploid patients (77% vs 63% at 3 years; P = .04), and
      this was more evident in patients treated with bortezomib, thalidomide, and
      prednisone (77% vs 53% at 3 years; P = .02). The present schema does not overcome
      the negative prognosis of high-risk CAs and nonhyperdiploidy. This trial was
      registered with www.ClinicalTrials.gov as NCT00443235.

PMID- 21900195
TI  - ETV6-RUNX1 promotes survival of early B lineage progenitor cells via a
      dysregulated erythropoietin receptor.
AB  - ETV6-RUNX1 gene fusion is usually an early, prenatal event in childhood acute
      lymphoblastic leukemia (ALL). Transformation results in the generation of a
      persistent (> 14 years) preleukemic clone, which postnatally converts to ALL
      after the acquisition of necessary secondary genetic alterations. Many cancer
      cells show some expression of the erythropoietin receptor (EPOR) gene, although
      the "functionality" of any EPOR complexes and their relevant signaling pathways
      in nonerythroid cells has not been validated. EPOR mRNA is selectively and
      ectopically expressed in ETV6-RUNX1(+) ALL, but the presence of a functional EPOR
      on the cell surface and its role in leukemogenesis driven by ETV6-RUNX1 remains
      to be identified. Here, we show that ETV6-RUNX1 directly binds the EPOR promoter
      and that expression of ETV6-RUNX1 alone in normal pre-B cells is sufficient to
      activate EPOR transcription. We further reveal that murine and human ETV6
      RUNX1(+) cells expressing EPOR mRNA have EPO ligand binding activity that
      correlates with an increased cell survival through activation of the JAK2-STAT5
      pathway and up-regulation of antiapoptotic BCL-XL. These data support the
      contention that ETV6-RUNX1 directly activates ectopic expression of a functional
      EPOR and provides cell survival signals that may contribute critically to
      persistence of covert premalignant clones in children.

PMID- 21900194
TI  - Genome-wide ChIP-Seq reveals a dramatic shift in the binding of the transcription
      factor erythroid Kruppel-like factor during erythrocyte differentiation.
AB  - Erythropoiesis is dependent on the activity of transcription factors, including
      the erythroid-specific erythroid Kruppel-like factor (EKLF). ChIP followed by
      massively parallel sequencing (ChIP-Seq) is a powerful, unbiased method to map
      trans-factor occupancy. We used ChIP-Seq to study the interactome of EKLF in
      mouse erythroid progenitor cells and more differentiated erythroblasts. We
      correlated these results with the nuclear distribution of EKLF, RNA-Seq analysis
      of the transcriptome, and the occupancy of other erythroid transcription factors.
      In progenitor cells, EKLF is found predominantly at the periphery of the nucleus,
      where EKLF primarily occupies the promoter regions of genes and acts as a
      transcriptional activator. In erythroblasts, EKLF is distributed throughout the
      nucleus, and erythroblast-specific EKLF occupancy is predominantly in intragenic
      regions. In progenitor cells, EKLF modulates general cell growth and cell cycle
      regulatory pathways, whereas in erythroblasts EKLF is associated with repression
      of these pathways. The EKLF interactome shows very little overlap with the
      interactomes of GATA1, GATA2, or TAL1, leading to a model in which EKLF directs
      programs that are independent of those regulated by the GATA factors or TAL1.

PMID- 21900197
TI  - Attenuation of leukocyte recruitment via CXCR1/2 inhibition stops the progression
      of PAH in mice with genetic ablation of endothelial BMPR-II.
AB  - Previous studies from our group have demonstrated that bone morphogenetic protein
      receptor-II (BMPR-II), expressed on pulmonary artery endothelial cells, imparts
      profound anti-inflammatory effects by regulating the release of proinflammatory
      cytokines and promoting barrier function by suppressing the transmigration of
      leukocytes into the pulmonary vessel wall. Here we demonstrate that, in mice with
      endothelial-specific loss of BMPR-II expression (L1Cre(+);Bmpr2(f/f)), reduction
      in barrier function and the resultant pulmonary hypertension observed in vivo are
      the result of increased leukocyte recruitment through increased CXCR1/2
      signaling. Loss of endothelial expressed BMPR-II leads to elevated plasma levels
      of a wide range of soluble mediators important in regulating leukocyte migration
      and extravasation, including the CXCR1/2 ligand, KC. Treatment of
      L1Cre(+);Bmpr2(f/f) mice with the CXCR1/2 antagonist SCH527123 inhibits leukocyte
      transmigration into lung and subsequently reverses the pulmonary hypertension.
      Our data have uncovered a previously unrecognized regulatory function of BMPR-II,
      which acts to regulate the expression of CXCR2 on endothelial cells, suggesting
      that increased CXCR2 signaling may also be a feature of the human pathology and
      that CXCR1/2 pathway antagonists may represent a novel therapeutic approach for
      treating pulmonary hypertension because of defects in BMPR-II expression.

PMID- 21900196
TI  - Low telomerase activity in CD4+ regulatory T cells in patients with severe
      chronic GVHD after hematopoietic stem cell transplantation.
AB  - CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) play an important role in the
      control of chronic graft-versus-host disease (cGVHD). In this study, we examined
      telomere length and telomerase activity of Treg and conventional CD4(+) T cells
      (Tcon) in 61 patients who survived more than 2 years after allogeneic
      hematopoietic stem cell transplantation. Cell proliferation and expression of Bcl
      2 were also measured in each subset. Treg telomere length was shorter and Treg
      telomerase activity was increased compared with Tcon (P < .0001). After
      transplantation, Treg were also more highly proliferative than Tcon (P < .0001).
      Treg number, telomerase activity, and expression of Bcl-2 were each inversely
      associated with severity of cGVHD. These data indicate that activation of
      telomerase is not sufficient to prevent telomere shortening in highly
      proliferative Treg. However, telomerase activation is associated with increased
      Bcl-2 expression and higher Treg numbers in patients with no or mild cGVHD. In
      contrast, patients with moderate or severe cGVHD have fewer Treg with lower
      levels of telomerase activity and Bcl-2 expression. These results suggest that
      failure to activate Treg telomerase may restrict proliferative capacity and
      increase apoptotic susceptibility, resulting in the loss of peripheral tolerance
      and the development of cGVHD.

PMID- 21900198
TI  - The impact of Fc-gamma receptor polymorphisms in elderly patients with diffuse
      large B-cell lymphoma treated with CHOP with or without rituximab.
AB  - Fcgamma receptor (FcgammaR) polymorphisms have been shown to affect rituximab
      mediated antibody-dependent cellular cytotoxicity. Of 512 patients with diffuse
      large B-cell lymphoma treated in the RICOVER-60 trial, carriers of FcgammaRIII
      158 valine homozygous receptors (V/V) presented with a slightly decreased
      incidence of B-symptoms (158 V/V: 26%, V/F: 35%, phenylalanine receptors [F/F]:
      42%; P = .037). Survival curves of all FcgammaR single nucleotide polymorphisms
      were superimposable after cyclophosphamide, doxorubicin, vincristine, and
      prednisone (CHOP); but after CHOP with rituximab (R-CHOP), event-free survival
      (EFS) and progression-free survival (PFS), but not overall survival, of
      FcgammaRIIIa 158 F/F had a trend to be lower than those of 158 V/F and 158 V/V: 3
      year EFS: FcgammaRIIIa 158 F/F: 64.5%, 158 V/F: 70.2%, 158 V/V: 76.9% (log-rank
      test: P = .224 F/F vs V/V; P = .285 F/F vs V/F + V/V); 3-year PFS: FcgammaRIIIa
      158 F/F: 68.3%, V/F: 76.1%, V/V: 80.5% (log-rank test: P = .233 for F/F vs V/V; P
      = .185 for F/F vs V/F + V/V). By multivariate analysis adjusting for
      International Prognostic Index factors, relative risk of F/F compared with V/F
      plus V/V was 1.80 (P = .052) for PFS and 1.55 (P = .120) for EFS. The interaction
      of R-CHOP, but not CHOP with FcgammaRIIIa polymorphisms, indicates a window of
      opportunity for CD20 antibodies designed to mediate enhanced antibody-dependent
      cellular cytotoxicity.

PMID- 21900199
TI  - BMP activity controlled by BMPER regulates the proinflammatory phenotype of
      endothelium.
AB  - The endothelium plays a pivotal role in vascular inflammation. Here we study bone
      morphogenetic protein (BMP) signaling in endothelial inflammation and in
      particular the role of BMPER, an extracellular BMP modulator that is important in
      vascular development and angiogenesis. Using the BMP antagonist dorsomorphin or
      BMP2 as an agonist we show that BMP signaling is essential for the inflammatory
      response of vascular endothelial cells as demonstrated by intravital microscopy.
      We found that BMPER is decreased in inflammation similar to vascular protective
      genes like KLF2 and eNOS. Using in vitro and in vivo models we show that BMPER is
      down-regulated through the TNFalpha-NFkappaB-KLF2 signaling pathway.
      Functionally, lack of BMPER induced by siRNA or in BMPER(+/-) mice confers a
      proinflammatory endothelial phenotype with reduced eNOS levels and enhanced
      expression of adhesion molecules leading to increased leukocyte adhesion and
      extravasation in ex vivo and in vivo experiments. Vice versa, addition of BMPER
      exerts endothelium protective functions and antagonizes TNFalpha induced
      inflammation. Mechanistically, we demonstrate that these effects of BMPER are
      dependent on BMP signaling because of enhanced NFkappaB activity. In conclusion,
      the BMP modulator BMPER is a new protective regulator of vascular inflammation
      that modulates leukocyte adhesion and migration in vitro and in vivo.

PMID- 21900200
TI  - Twenty-one cases of blastic plasmacytoid dendritic cell neoplasm: focus on
      biallelic locus 9p21.3 deletion.
AB  - Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive
      malignancy derived from precursors of plasmacytoid dendritic cells. We analyzed
      21 cases with array-based comparative genomic hybridization (aCGH). Complete or
      partial chromosomal losses largely outnumbered the gains, with common deleted
      regions involving 9p21.3 (CDKN2A/CDKN2B), 13q13.1-q14.3 (RB1), 12p13.2-p13.1
      (CDKN1B), 13q11-q12 (LATS2), and 7p12.2 (IKZF1) regions. CDKN2A/CDKN2B deletion
      was confirmed by FISH. This scenario argues for disruption of cell cycle at
      G(1)/S transition, representing a genetic landmark of BPDCN, and possibly
      contributing to its pathogenesis. Statistical analysis of overall survival in our
      series highlighted an association of poor outcome with biallelic loss of locus
      9p21.3. We suggest that, in the absence of reliable parameters for predicting
      prognosis in BPDCN other than age, tumor stage, and/or clinical presentation,
      simple methods, such as FISH for CDKN2A/CDKN2B, could help to identify the most
      aggressive cases.

PMID- 21900201
TI  - C-terminal domain of MEIS1 converts PKNOX1 (PREP1) into a HOXA9-collaborating
      oncoprotein.
AB  - The three-amino-acid loop extension (TALE) class homeodomain proteins MEIS1 and
      PKNOX1 (PREP1) share the ability to interact with PBX and HOX family members and
      bind similar DNA sequences but appear to play opposing roles in tumor
      development. Elevated levels of MEIS1 accelerate development of HOX- and MLL
      induced leukemias, and this pro-tumorigenic property has been associated with
      transcriptional activity of MEIS1. In contrast, reduction of PKNOX1 levels has
      been linked with cancer development despite the absence of an identifiable
      transactivating domain. In this report, we show that a chimeric protein generated
      by fusion of the MEIS1 C-terminal region encompassing the transactivating domain
      with the full-length PKNOX1 (PKNOX1-MC) acquired the ability to accelerate the
      onset of Hoxa9-induced leukemia in the mouse bone marrow
      transduction/transplantation model. Gene expression profiling of primary bone
      marrow cells transduced with Hoxa9 plus Meis1, or Hoxa9 plus Pknox1-MC revealed
      perturbations in overlapping functional gene subsets implicated in DNA packaging,
      chromosome organization, and in cell cycle regulation. Together, results
      presented in this report suggest that the C-terminal domain of MEIS1 confers to
      PKNOX1 an ectopic transactivating function that promotes leukemogenesis by
      regulating expression of genes involved in chromatin accessibility and cell cycle
      progression.

PMID- 21900202
TI  - Optimization and application of median filter corrections to relieve diverse
      spatial patterns in microtiter plate data.
AB  - The standard (STD) 5 * 5 hybrid median filter (HMF) was previously described as a
      nonparametric local backestimator of spatially arrayed microtiter plate (MTP)
      data. As such, the HMF is a useful tool for mitigating global and sporadic
      systematic error in MTP data arrays. Presented here is the first known HMF
      correction of a primary screen suffering from systematic error best described as
      gradient vectors. Application of the STD 5 * 5 HMF to the primary screen raw data
      reduced background signal deviation, thereby improving the assay dynamic range
      and hit confirmation rate. While this HMF can correct gradient vectors, it does
      not properly correct periodic patterns that may present in other screening
      campaigns. To address this issue, 1 * 7 median and a row/column 5 * 5 hybrid
      median filter kernels (1 * 7 MF and RC 5 * 5 HMF) were designed ad hoc, to better
      fit periodic error patterns. The correction data show periodic error in simulated
      MTP data arrays is reduced by these alternative filter designs and that multiple
      corrective filters can be combined in serial operations for progressive reduction
      of complex error patterns in a MTP data array.

PMID- 21900203
TI  - Focus issue: series on computational and systems biology.
AB  - The application of computational biology and systems biology is yielding
      quantitative insight into cellular regulatory phenomena. For the month of
      September, Science Signaling highlights research featuring computational
      approaches to understanding cell signaling and investigation of signaling
      networks, a series of Teaching Resources from a course in systems biology, and
      various other articles and resources relevant to the application of computational
      biology and systems biology to the study of signal transduction.

PMID- 21900204
TI  - Crowdsourcing network inference: the DREAM predictive signaling network
      challenge.
AB  - Computational analyses of systematic measurements on the states and activities of
      signaling proteins (as captured by phosphoproteomic data, for example) have the
      potential to uncover uncharacterized protein-protein interactions and to identify
      the subset that are important for cellular response to specific biological
      stimuli. However, inferring mechanistically plausible protein signaling networks
      (PSNs) from phosphoproteomics data is a difficult task, owing in part to the lack
      of sufficiently comprehensive experimental measurements, the inherent limitations
      of network inference algorithms, and a lack of standards for assessing the
      accuracy of inferred PSNs. A case study in which 12 research groups inferred PSNs
      from a phosphoproteomics data set demonstrates an assessment of inferred PSNs on
      the basis of the accuracy of their predictions. The concurrent prediction of the
      same previously unreported signaling interactions by different participating
      teams suggests relevant validation experiments and establishes a framework for
      combining PSNs inferred by multiple research groups into a composite PSN. We
      conclude that crowdsourcing the construction of PSNs-that is, outsourcing the
      task to the interested community-may be an effective strategy for network
      inference.

PMID- 21900206
TI  - A directed protein interaction network for investigating intracellular signal
      transduction.
AB  - Cellular signal transduction is a complex process involving protein-protein
      interactions (PPIs) that transmit information. For example, signals from the
      plasma membrane may be transduced to transcription factors to regulate gene
      expression. To obtain a global view of cellular signaling and to predict
      potential signal modulators, we searched for protein interaction partners of more
      than 450 signaling-related proteins by means of automated yeast two-hybrid
      interaction mating. The resulting PPI network connected 1126 proteins through
      2626 PPIs. After expansion of this interaction map with publicly available PPI
      data, we generated a directed network resembling the signal transduction flow
      between proteins with a naive Bayesian classifier. We exploited information on
      the shortest PPI paths from membrane receptors to transcription factors to
      predict input and output relationships between interacting proteins. Integration
      of directed PPI with time-resolved protein phosphorylation data revealed network
      structures that dynamically conveyed information from the activated epidermal
      growth factor and extracellular signal-regulated kinase (EGF/ERK) signaling
      cascade to directly associated proteins and more distant proteins in the network.
      From the model network, we predicted 18 previously unknown modulators of EGF/ERK
      signaling, which we validated in mammalian cell-based assays. This generic
      experimental and computational approach provides a framework for elucidating
      causal connections between signaling proteins and facilitates the identification
      of proteins that modulate the flow of information in signaling networks.

PMID- 21900205
TI  - Small molecule-mediated activation of the integrin CD11b/CD18 reduces
      inflammatory disease.
AB  - The integrin CD11b/CD18 (also known as Mac-1), which is a heterodimer of the
      alpha(M) (CD11b) and beta(2) (CD18) subunits, is critical for leukocyte adhesion
      and migration and for immune functions. Blocking integrin-mediated leukocyte
      adhesion, although beneficial in experimental models, has had limited success in
      treating inflammatory diseases in humans. Here, we used an alternative strategy
      of inhibiting leukocyte recruitment by activating CD11b/CD18 with small-molecule
      agonists, which we term leukadherins. These compounds increased the extent of
      CD11b/CD18-dependent cell adhesion of transfected cells and of primary human and
      mouse neutrophils, which resulted in decreased chemotaxis and transendothelial
      migration. Leukadherins also decreased leukocyte recruitment and reduced arterial
      narrowing after injury in rats. Moreover, compared to a known integrin
      antagonist, leukadherins better preserved kidney function in a mouse model of
      experimental nephritis. Leukadherins inhibited leukocyte recruitment by
      increasing leukocyte adhesion to the inflamed endothelium, which was reversed
      with a blocking antibody. Thus, we propose that pharmacological activation of
      CD11b/CD18 offers an alternative therapeutic approach for inflammatory diseases.

PMID- 21900208
TI  - Setting new tracks: not just creating another pretty picture.

PMID- 21900207
TI  - Gene set enrichment analysis: performance evaluation and usage guidelines.
AB  - A central goal of biology is understanding and describing the molecular basis of
      plasticity: the sets of genes that are combinatorially selected by exogenous and
      endogenous environmental changes, and the relations among the genes. The most
      viable current approach to this problem consists of determining whether sets of
      genes are connected by some common theme, e.g. genes from the same pathway are
      overrepresented among those whose differential expression in response to a
      perturbation is most pronounced. There are many approaches to this problem, and
      the results they produce show a fair amount of dispersion, but they all fall
      within a common framework consisting of a few basic components. We critically
      review these components, suggest best practices for carrying out each step, and
      propose a voting method for meeting the challenge of assessing different methods
      on a large number of experimental data sets in the absence of a gold standard.

PMID- 21900209
TI  - Time-frequency analysis of single pulse electrical stimulation to assist
      delineation of epileptogenic cortex.
AB  - Epilepsy surgery depends on reliable pre-surgical markers of epileptogenic
      tissue. The current gold standard is the seizure onset zone in ictal, i.e.
      chronic, electrocorticography recordings. Single pulse electrical stimulation can
      evoke epileptic, spike-like responses in areas of seizure onset also recorded by
      electrocorticography. Recently, spontaneous pathological high-frequency
      oscillations (80-520 Hz) have been observed in the electrocorticogram that are
      related to epileptic spikes, but seem more specific for epileptogenic cortex. We
      wanted to see whether a quantitative electroencephalography analysis using time
      frequency information including the higher frequency range could be applied to
      evoked responses by single pulse electrical stimulation, to enhance its
      specificity and clinical use. Electrocorticography data were recorded at a 2048
      Hz sampling rate from 13 patients. Single pulse electrical stimulation (10
      stimuli, 1 ms, 8 mA, 0.2 Hz) was performed stimulating pairs of adjacent
      electrodes. A time-frequency analysis based on Morlet wavelet transformation was
      performed in a [-1 s : 1 s] time interval around the stimulus and a frequency
      range of 10-520 Hz. Significant (P = 0.05) changes in power spectra averaged for
      10 epochs were computed, resulting in event-related spectral perturbation images.
      In these images, time-frequency analysis of single pulse-evoked responses, in the
      range of 10-80 Hz for spikes, 80-250 Hz for ripples and 250-520 Hz for fast
      ripples, were scored by two observers independently. Sensitivity, specificity and
      predictive value of time-frequency single pulse-evoked responses in the three
      frequency ranges were compared with seizure onset zone and post-surgical outcome.
      In all patients, evoked responses included spikes, ripples and fast ripples. For
      the seizure onset zone, the median sensitivity of time-frequency single pulse
      evoked responses decreased from 100% for spikes to 67% for fast ripples and the
      median specificity increased from 17% for spikes to 79% for fast ripples. A
      median positive predictive value for the evoked responses in the seizure onset
      zone of 17% was found for spikes, 26% for ripples and 37% for fast ripples. Five
      out of seven patients with <50% of fast ripples removed by resection had a poor
      outcome. A wavelet transform-based time-frequency analysis of single pulse
      electrical stimulation reveals evoked responses in the frequency range of spikes,
      ripples and fast ripples. We demonstrate that time-frequency analysis of single
      pulse electrical stimulation can assist in delineation of the epileptogenic
      cortex using time-frequency single pulse-evoked fast ripples as a potential new
      marker.

PMID- 21900210
TI  - Rapid decrease in horn size of bighorn sheep: environmental decline, inbreeding
      depression, or evolutionary response to trophy hunting?
AB  - There are numerous examples demonstrating that selection has greatly influenced
      phenotypes in wild-harvested species. Here, a significant reduction in horn size
      in trophy desert bighorn sheep rams over 30 years in a reintroduced population in
      Aravaipa Canyon, Arizona is documented. After examining the potential effects of
      a detrimental change in the environment, inbreeding depression, and hunter-caused
      evolutionary change, it appears that environmental deterioration, apparently from
      the effects of drought, may be a major cause of the decline in horn size. In
      particular, the reduction in ram horn size is positively associated with reduced
      winter lifetime rainfall over the 3 decades. Over the same period, the
      demographic indicator lamb-to-ewe ratio has also declined in the Aravaipa
      population. On the other hand, lamb-to-ewe ratio has not declined statewide in
      Arizona, and the population size in Aravaipa appears to be increasing, suggesting
      local- and trait-specific effects. Using a theoretical context, neither
      inbreeding depression nor hunter selection by themselves appear to the sole
      causes of the lower horn size. However, some combination of environmental
      factors, inbreeding depression, and hunter selection may have caused the decrease
      in observed horn size. It is not clear what management actions might be
      successful in countering the environmental effects on horn size, but supplemental
      feeding and cattle removal are suggested while translocation is suggested to
      counter the effects of inbreeding depression and reduced hunting and
      translocation are suggested to counter the effects of hunter selection.

PMID- 21900211
TI  - Transcriptional activity of ATF3 in the stromal compartment of tumors promotes
      cancer progression.
AB  - Compelling evidences have rendered the tumor microenvironment a crucial
      determinant in cancer outcome. Activating transcription factor 3 (ATF3), a stress
      response transcription factor, is known to have a dichotomous role in tumor
      cells, acting either as a tumor suppressor or an oncogene in a context-dependent
      manner. However, its expression and possible role in the tumor microenvironment
      are hitherto unknown. Here we show that ATF3 is upregulated in the stromal
      compartment of several types of cancer. Accordingly, Cancer-associated
      fibroblasts (CAFs) ectopically expressing ATF3 proliferated faster as indicated
      by increased colony-forming capacity and promoted the growth of adjacent tumor
      cells when co-injected into nude mice. Utilizing a genome-wide profiling
      approach, we unraveled a robust gene expression program induced by ATF3 in CAFs.
      Focusing on a specific subset of genes, we found that the ability of stromal ATF3
      to promote cancer progression is mediated by transcriptional repression of CLDN1
      and induction of CXCL12 and RGS4. In addition, regulation of LIF, CLDN1,
      SERPINE2, HSD17B2, ITGA7 and PODXL by ATF3 mediated the increased proliferation
      capacity of CAFs. In sum, our findings implicate ATF3 as a novel stromal tumor
      promoter and suggest that targeting ATF3 pathway might be beneficial for
      anticancer therapy.

PMID- 21900212
TI  - Altered tissue distribution of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
      DNA adducts in mice transgenic for human sulfotransferases 1A1 and 1A2.
AB  - Soluble sulfotransferases (SULTs) generate electrophilically reactive metabolites
      from numerous food-borne compounds, environmental contaminants and drugs, often
      resulting in mutagenicity and carcinogenicity. Substrate specificity, regulation
      and tissue distribution of SULTs show large interspecies differences. In humans,
      therefore, SULTs may be involved in the induction of cancer in different tissues
      than in standard animal models. To construct a rodent model taking some species
      differences into account, we transferred a 68.5 kb human (h) genomic sequence
      that comprised the transcribed and long flanking regions of SULT1A1 and 1A2 into
      murine oocytes. This approach resulted in several mouse lines expressing these
      human genes in a copy number-dependent manner with a tissue distribution similar
      to that in humans. In previous in vitro studies, we had demonstrated that human
      SULT1A1 and 1A2 efficiently catalyze the terminal activation of 2-amino-1-methyl
      6-phenylimidazo[4,5-b]pyridine (PhIP) to a mutagen. The transgenic mice were used
      to study the hSULT1A1/1A2-mediated activation. Tissue distribution and levels of
      DNA adducts were determined in hSULT1A1/1A2 transgenic and wild-type mice after
      an oral dosage of PhIP. Transgenic mice exhibited significantly elevated PhIP-DNA
      adduct levels compared with the wild-type in liver (13-fold), lung (3.8-fold),
      colon (2-fold), kidney (1.6-fold) and cecum (1.5-fold). Moreover, among the eight
      tissues examined, liver was the one with the lowest and highest adduct levels in
      wild-type and transgenic mice, respectively. Hence, expression of hSULT1A1/1A2
      not only enhanced the genotoxicity but also substantially changed the
      organotropism of PhIP.

PMID- 21900215
TI  - Crescendos and decrescendos: gastric and esophageal cancers.

PMID- 21900213
TI  - Whole-genome sequencing of sake yeast Saccharomyces cerevisiae Kyokai no. 7.
AB  - The term 'sake yeast' is generally used to indicate the Saccharomyces cerevisiae
      strains that possess characteristics distinct from others including the
      laboratory strain S288C and are well suited for sake brewery. Here, we report the
      draft whole-genome shotgun sequence of a commonly used diploid sake yeast strain,
      Kyokai no. 7 (K7). The assembled sequence of K7 was nearly identical to that of
      the S288C, except for several subtelomeric polymorphisms and two large inversions
      in K7. A survey of heterozygous bases between the homologous chromosomes revealed
      the presence of mosaic-like uneven distribution of heterozygosity in K7. The
      distribution patterns appeared to have resulted from repeated losses of
      heterozygosity in the ancestral lineage of K7. Analysis of genes revealed the
      presence of both K7-acquired and K7-lost genes, in addition to numerous others
      with segmentations and terminal discrepancies in comparison with those of S288C.
      The distribution of Ty element also largely differed in the two strains.
      Interestingly, two regions in chromosomes I and VII of S288C have apparently been
      replaced by Ty elements in K7. Sequence comparisons suggest that these gene
      conversions were caused by cDNA-mediated recombination of Ty elements. The
      present study advances our understanding of the functional and evolutionary
      genomics of the sake yeast.

PMID- 21900216
TI  - Drug shortages: impact and strategies.

PMID- 21900217
TI  - Proton therapy in an era of cost containment.

PMID- 21900218
TI  - Esophageal and esophagogastric junction cancers.

PMID- 21900219
TI  - Endoscopic therapy of esophageal premalignancy and early malignancy.
AB  - Esophageal adenocarcinoma (EAC) is an often deadly cancer with a rising incidence
      in Western countries. Chronic gastroesophageal reflux disease is associated with
      the metaplastic transformation of normal squamous epithelium to premalignant
      specialized intestinal metaplasia within the esophagus (Barrett's esophagus).
      Barrett's esophagus may progress to low-grade dysplasia (LGD), high-grade
      dysplasia (HGD), or even EAC. Although nondysplastic Barrett's esophagus
      progresses to EAC at a rate of 0.5% per year, rates of progression for true LGD
      and HGD are significantly higher. Treatment is mandatory for HGD and may be
      appropriate in select patients with nondysplastic Barrett's esophagus and many
      with LGD. Thus, accurate pathologic assessment is necessary before considering
      endoscopic therapy. Previously, only esophagectomy was offered to patients with
      HGD or EAC. However, esophagectomy has significant morbidity and mortality, and
      therefore endoscopic therapies have been advocated for early Barrett's neoplasia.
      These methods include endoscopic mucosal resection (EMR) and ablative techniques.
      Ablation techniques include argon plasma coagulation, multipolar
      electrocoagulation, laser therapy, photodynamic therapy, radiofrequency ablation,
      and cryotherapy. Of these, radiofrequency ablation has experienced the greatest
      adoption for the treatment of dysplastic Barrett's esophagus because of excellent
      published outcomes. The use of EMR to resect suspicious areas or raised lesions
      is mandatory to provide histology. In contrast, ablation techniques such as
      radiofrequency ablation have been shown to effectively eradicate large areas of
      dysplastic tissue with relative ease but do not allow for histologic assessment
      of the treated area. Combination EMR with radiofrequency ablation is thus
      advocated to resect visible lesions via EMR (providing histology) and ablate the
      remainder of the Barrett's esophagus. As always, the appropriate treatment is
      best determined after careful discussion with patients in a multidisciplinary
      environment. However, endoscopic therapy offers an attractive alternative to
      esophagectomy for early Barrett's neoplasia.

PMID- 21900220
TI  - Modern approaches to localized cancer of the esophagus.
AB  - The clinical spectrum of esophageal cancer has changed dramatically over the past
      couple of decades. Most notably, a profound rise in esophageal adenocarcinoma and
      decrease in the incidence of squamous carcinomas have occurred. An understanding
      of the factors that influence survival for patients with localized esophageal
      cancer has evolved concomitantly with these changes in epidemiology. Significant
      advancement in endoscopic and radiographic staging allows for more selective use
      of treatment modalities. The treatment of localized esophageal cancer mandates a
      multidisciplinary approach, with treatment tailored to disease extent, location,
      histology, and an accurate assessment of pretreatment staging. Despite these
      improvements in the staging and use of multimodality therapy, only modest
      improvements in patient survival have been observed. This article summarizes
      these modern approaches to localized cancer of the esophagus.

PMID- 21900221
TI  - Myeloid growth factors.

PMID- 21900222
TI  - Biosimilars: are they ready for primetime in the United States?
AB  - The introduction of alternative versions of biologic products, also known as
      biosimilars, into the United States market has been gaining increasing visibility
      as patents for many agents are nearing expiration. Unlike generics, which are
      regulated under the Hatch-Waxman legislation passed in 1984, the approval process
      for biosimilars in the United States has not been defined. In 2004, the European
      Union established a regulatory pathway for these agents, and the FDA is now
      following suit. The economic implications are large, with $66.9 billion spent on
      the top 20 biologics in 2009. Of the top 10 biologics, 6 are routinely used in
      oncology. As the regulatory requirements are debated, several critical issues
      must be resolved. The most obvious is that the agents must be shown to be
      comparable to the original biologic they intend to replace. Knowledge of
      pharmacokinetic parameters alone will not be adequate, but the amount of clinical
      data required by the FDA remains unclear. The regulations will define the ease
      with which a biosimilar can be brought to market, and the associated costs of
      trials will influence the ultimate price of the medications. Balancing the needs
      of the relevant stakeholders is critical to ensure patient safety while
      controlling costs, improving access, and encouraging innovation. This is not an
      easy balance to strike.

PMID- 21900223
TI  - Long-term outcomes of myeloid growth factor treatment.
AB  - Myeloid growth factors are used to reduce myelotoxicity and the risk of infection
      after cancer chemotherapy and in patients with chronic neutropenia. This article
      addresses the long-term benefits and risks associated with granulocyte colony
      stimulating factor (G-CSF) therapy in both settings. A systematic review of
      randomized controlled trials recently reported long-term outcomes regarding the
      risk of second malignancies and overall survival. Based on these studies, the
      risk for acute myeloid leukemia (AML) associated with known carcinogenic agents,
      such as chemotherapy, could not be distinguished from any risk associated with
      growth factor support. However, the enhanced delivery of chemotherapy dose
      intensity enabled by the use of G-CSF in these studies was associated with a
      significant reduction in all-cause mortality. Although some reduction in
      treatment-related mortality with G-CSF support may occur, the observed
      improvement in long-term survival likely relates to better disease control with
      more-intense G-CSF-supported chemotherapy. Myeloid growth factors have also been
      shown to benefit patients with severe chronic neutropenia. Almost all patients
      with cyclic, congenital, or idiopathic neutropenia experience response to G-CSFs.
      Treatment is titrated to determine a dose that provides a safe elevation in
      neutrophil counts. Reports have shown that patients can be maintained for years
      at the same dose after adjusting for growth and development. In congenital
      neutropenia, the inherent risk of developing myelodysplastic syndromes or AML
      requires careful monitoring, including routine blood counts and annual bone
      marrow examinations.

PMID- 21900225
TI  - Minor salivary gland biopsy in diagnosing ocular sarcoidosis.
AB  - BACKGROUND: To ascertain the sensitivity, specificity, and positive and negative
      predictive value of minor salivary gland biopsy in subsets of patients with
      uveitis consistent with ocular sarcoidosis. METHOD: Minor salivary gland biopsies
      performed in 230 patients with uveitis of indeterminate origin but clinically
      compatible with ocular sarcoidosis were reviewed. The biopsy results were
      analysed together with clinical features of uveitis and with the results of other
      relevant examinations, such as serum levels of angiotensin-I-converting enzyme
      and lysozyme, tuberculin skin test, chest radiography or CT scan, pulmonary
      function tests and bronchoalveolar lavage. RESULTS: Only seven of the 230
      patients with uveitis had sarcoid granulomas on the minor salivary gland biopsy.
      All seven of these patients had a granulomatous uveitis and a compatible chest x
      ray with sarcoidosis. The profitability of minor salivary gland biopsy can be
      improved by limiting the procedure to patients having granulomatous uveitis and a
      compatible chest x-ray. In these conditions, the positivity rate of minor
      salivary gland biopsy increased from 3% to 24% without loss of sensitivity.
      CONCLUSION: Minor salivary gland biopsy is most useful for assessing the
      diagnosis of sarcoid uveitis in a second-line investigation for patients with
      granulomatous uveitis and a radiologic pattern compatible with sarcoidosis.

PMID- 21900224
TI  - Cost-effectiveness of internal limiting membrane peeling versus no peeling for
      patients with an idiopathic full-thickness macular hole: results from a
      randomised controlled trial.
AB  - AIM: To determine whether internal limiting membrane (ILM) peeling is cost
      effective compared with no peeling for patients with an idiopathic stage 2 or 3
      full-thickness macular hole. METHODS: A cost-effectiveness analysis was performed
      alongside a randomised controlled trial. 141 participants were randomly allocated
      to receive macular-hole surgery, with either ILM peeling or no peeling. Health
      service resource use, costs and quality of life were calculated for each
      participant. The incremental cost per quality-adjusted life year (QALY) gained
      was calculated at 6 months. RESULTS: At 6 months, the total costs were on average
      higher (L424, 95% CI -182 to 1045) in the No Peel arm, primarily owing to the
      higher reoperation rate in the No Peel arm. The mean additional QALYs from ILM
      peel at 6 months were 0.002 (95% CI 0.01 to 0.013), adjusting for baseline EQ-5D
      and other minimisation factors. A mean incremental cost per QALY was not
      computed, as Peeling was on average less costly and slightly more effective. A
      stochastic analysis suggested that there was more than a 90% probability that
      Peeling would be cost-effective at a willingness-to-pay threshold of L20,000 per
      QALY. CONCLUSION: Although there is no evidence of a statistically significant
      difference in either costs or QALYs between macular hole surgery with or without
      ILM peeling, the balance of probabilities is that ILM Peeling is likely to be a
      cost-effective option for the treatment of macular holes. Further long-term
      follow-up data are needed to confirm these findings.

PMID- 21900226
TI  - Long-term results of office-based pneumatic retinopexy using pure air.
AB  - AIMS: The long-term results of office-based pneumatic retinopexy (PR) using only
      filtered air were evaluated in a case series of rhegmatogenous retinal
      detachments with more than 3 years of follow-up, on average. METHODS: 77 cases of
      primary rhegmatogenous retinal detachments arising from superior tears (mean=1.6
      tears) were treated with cryopexy (n=61) or laser (next day, n=16) and
      intravitreal injection of pure air in an office setting. The macula was detached
      preoperatively in 37 eyes (48.1%). Outcome measures were single-operation
      success, final reattachment rates and visual acuity (VA). RESULTS: Subjects were
      followed for 6-186 months (mean follow-up = 40.7 months, 46.8% >= 2 years, 25% >=
      5 years). In all cases, the air bubble was gone within 5 days. Single-operation
      success was achieved in 62/77 (80.5%) eyes. Repeat PR was successful in four
      cases, increasing the PR reattachment rate to 85.7%. Scleral buckle was performed
      on the remaining 11 eyes (14.3%), 1 with vitrectomy. The final reattachment rate
      was 100%. VA improved >= 2 Snellen lines in 53.2% of patients, with 50/77 (64.9%)
      attaining VA >= 20/40. Following PR, 87% of subjects had the same or better VA.
      CONCLUSIONS: Office-based pure-air PR achieves acceptable reattachment rates with
      good visual outcomes and long-term efficacy. Eliminating the need for expansile
      gases makes this approach more widely available, decreases recovery time and
      lowers healthcare costs.

PMID- 21900227
TI  - Variation in optical coherence tomography signal quality as an indicator of
      retinal nerve fibre layer segmentation error.
AB  - PURPOSE: Commercial optical coherence tomography (OCT) systems use global signal
      quality indices to quantify scan quality. Signal quality can vary throughout a
      scan, contributing to local retinal nerve fibre layer segmentation errors (SegE).
      The purpose of this study was to develop an automated method, using local scan
      quality, to predict SegE. METHODS: Good-quality (global signal strength (SS) >=
      6; manufacturer specification) peripapillary circular OCT scans (fast retinal
      nerve fibre layer scan protocol; Stratus OCT; Carl Zeiss Meditec, Dublin,
      California, USA) were obtained from 6 healthy, 19 glaucoma-suspect and 43
      glaucoma subjects. Scans were grouped based on SegE. Quality index (QI) values
      were computed for each A-scan using software of our own design. Logistic mixed
      effects regression modelling was applied to evaluate SS, global mean and SD of
      QI, and the probability of SegE. RESULTS: The difference between local mean QI in
      SegE regions and No-SegE regions was -5.06 (95% CI -6.38 to 3.734) (p<0.001).
      Using global mean QI, QI SD and their interaction term resulted in the model of
      best fit (Akaike information criterion=191.8) for predicting SegE. Global mean QI
      >= 20 or SS >= 8 shows little chance for SegE. Once mean QI<20 or SS<8, the
      probability of SegE increases as QI SD increases. CONCLUSIONS: When combined with
      a signal quality parameter, the variation of signal quality between A-scans
      provides significant information about the quality of an OCT scan and can be used
      as a predictor of segmentation error.

PMID- 21900229
TI  - Hemi-automated lamellar keratoplasty (HALK).
AB  - AIM: To describe a hybrid technique for anterior lamellar keratoplasty in corneas
      with topographical irregularities that circumvents the limitations of the
      microkeratome, namely reproduction of surface irregularities in the lamellar cut
      when creating the recipient flap. METHOD: Hemi-automated lamellar keratoplasty, a
      procedure that combines manual recipient bed lamellar dissection with automated
      donor preparation using a microkeratome, was performed on 14 eyes of 14 patients
      with heterogeneous causes of anterior stromal scarring. RESULTS: There was an
      overall improvement in uncorrected visual acuity (UCVA) in 78.6% (11/14) eyes and
      in best-corrected visual acuity (BCVA) in 78.6% (11/14) eyes at a mean of 9
      months postoperatively. Mean preoperative and postoperative logMAR UCVAs were
      1.31 +/- 0.74 and 0.83 +/- 0.46 (p=0.04), respectively. Mean preoperative and
      postoperative logMAR BCVAs were 0.72 +/- 0.58 and 0.38 +/- 0.23 (p=0.05). Mean
      preoperative and postoperative manifest refractive spherical equivalents were 
      0.76 +/- 3.61 D and -0.52 +/- 3.44 D (p=0.872). There was no difference in
      preoperative and postoperative sphere and cylinder (p=0.871 and 0.965,
      respectively). In a subset of six eyes with longer follow-up >12 months, the UCVA
      and BCVA show continuing improvement. All grafts remained clear at the final
      appointment. CONCLUSIONS: Hemi-automated lamellar keratoplasty is an effective
      and safe surgical procedure in the treatment of corneas with irregular
      topographic profiles with varying depths of anterior stromal scarring. It
      combines the benefits of smooth microkeratome lamellar dissection of the donor
      with customised lenticule thickness and diameter together with a manual lamellar
      dissection technique for the recipient providing encouraging visual outcomes that
      show continuing improvement with time.

PMID- 21900228
TI  - 'Cone dystrophy with supranormal rod response' in children.
AB  - AIM: To describe the initial clinical presentation of children with 'cone
      dystrophy with supranormal rod response,' a distinct retinal disorder from
      recessive KCNV2 mutations. METHODS: Retrospective case series. RESULTS: Nine
      children (seven families) initially examined from 2 to 8 years of age were
      identified. Three had a similar initial presentation of abnormal head position
      with head shaking and nystagmus, while the other six presented with either
      infantile nystagmus (without abnormal head position or head shaking), suspected
      congenital glaucoma (with associated nystagmus), intermittent exotropia, V
      pattern esotropia, comitant esotropia or difficulty with near vision only
      (reading). Only two children had clinically evident retinal changes (macular
      discoloration), and only two had a myopic cycloplegic refraction (the child with
      infantile nystagmus and the glaucoma suspect who actually had megalocornea). In
      addition to cone dystrophy, ERGs showed delayed scotopic responses with
      supranormal (six), high normal (two) or normal (one) scotopic b-wave responses to
      bright flash. Only one ERG (with a supranormal response) did not show a broad a
      wave trough response to scotopic flash. For all patients, KCNV2 sequencing
      revealed one of three homozygous recessive mutations (one previously reported
      (p.E143X), two novel (p.Y53X, p.E80D)). The three children who presented with an
      abnormal head position, head shaking and nystagmus and the child who presented
      with infantile nystagmus had several years' follow-up, during which these
      findings resolved (two) or decreased (two). CONCLUSIONS: Initial clinical
      presentation varied, the most common presentation being abnormal head position,
      head shaking and nystagmus that improved with time. ERG findings are
      characteristic and specific for KCNV2 mutations but do not necessarily include a
      scotopic b-wave flash response that is supranormal under standard ERG conditions.

PMID- 21900230
TI  - Structural basis for leucine-induced allosteric activation of glutamate
      dehydrogenase.
AB  - Glutamate dehydrogenase (GDH) catalyzes reversible conversion between glutamate
      and 2-oxoglutarate using NAD(P)(H) as a coenzyme. Although mammalian GDH is
      regulated by GTP through the antenna domain, little is known about the mechanism
      of allosteric activation by leucine. An extremely thermophilic bacterium, Thermus
      thermophilus, possesses GDH with a unique subunit configuration composed of two
      different subunits, GdhA (regulatory subunit) and GdhB (catalytic subunit). T.
      thermophilus GDH is unique in that the enzyme is subject to allosteric activation
      by leucine. To elucidate the structural basis for leucine-induced allosteric
      activation of GDH, we determined the crystal structures of the GdhB-Glu and GdhA
      GdhB-Leu complexes at 2.1 and 2.6 A resolution, respectively. The GdhB-Glu
      complex is a hexamer that binds 12 glutamate molecules: six molecules are bound
      at the substrate-binding sites, and the remaining six are bound at subunit
      interfaces, each composed of three subunits. The GdhA-GdhB-Leu complex is
      crystallized as a heterohexamer composed of four GdhA subunits and two GdhB
      subunits. In this complex, six leucine molecules are bound at subunit interfaces
      identified as glutamate-binding sites in the GdhB-Glu complex. Consistent with
      the structure, replacement of the amino acid residues of T. thermophilus GDH
      responsible for leucine binding made T. thermophilus GDH insensitive to leucine.
      Equivalent amino acid replacement caused a similar loss of sensitivity to leucine
      in human GDH2, suggesting that human GDH2 also uses the same allosteric site for
      regulation by leucine.

PMID- 21900231
TI  - Structure of a ternary Naa50p (NAT5/SAN) N-terminal acetyltransferase complex
      reveals the molecular basis for substrate-specific acetylation.
AB  - The co-translational modification of N-terminal acetylation is ubiquitous among
      eukaryotes and has been reported to have a wide range of biological effects. The
      human N-terminal acetyltransferase (NAT) Naa50p (NAT5/SAN) acetylates the alpha
      amino group of proteins containing an N-terminal methionine residue and is
      essential for proper sister chromatid cohesion and chromosome condensation. The
      elevated activity of NATs has also been correlated with cancer, making these
      enzymes attractive therapeutic targets. We report the x-ray crystal structure of
      Naa50p bound to a native substrate peptide fragment and CoA. We found that the
      peptide backbone of the substrate is anchored to the protein through a series of
      backbone hydrogen bonds with the first methionine residue specified through
      multiple van der Waals contacts, together creating an alpha-amino methionine
      specific pocket. We also employed structure-based mutagenesis; the results
      support the importance of the alpha-amino methionine-specific pocket of Naa50p
      and are consistent with the proposal that conserved histidine and tyrosine
      residues play important catalytic roles. Superposition of the ternary Naa50p
      complex with the peptide-bound Gcn5 histone acetyltransferase revealed that the
      two enzymes share a Gcn5-related N-acetyltransferase fold but differ in their
      respective substrate-binding grooves such that Naa50p can accommodate only an
      alpha-amino substrate and not a side chain lysine substrate that is acetylated by
      lysine acetyltransferase enzymes such as Gcn5. The structure of the ternary
      Naa50p complex also provides the first molecular scaffold for the design of NAT
      specific small molecule inhibitors with possible therapeutic applications.

PMID- 21900232
TI  - Delineation of lipopolysaccharide (LPS)-binding sites on hemoglobin: from in
      silico predictions to biophysical characterization.
AB  - Hemoglobin (Hb) functions as a frontline defense molecule during infection by
      hemolytic microbes. Binding to LPS induces structural changes in cell-free Hb,
      which activates the redox activity of the protein for the generation of
      microbicidal free radicals. Although the interaction between Hb and LPS has
      implications for innate immune defense, the precise LPS-interaction sites on Hb
      remain unknown. Using surface plasmon resonance, we found that both the Hb alpha
      and beta subunits possess high affinity LPS-binding sites, with K(D) in the
      nanomolar range. In silico analysis of Hb including phospho-group binding site
      prediction, structure-based sequence comparison, and docking to model the protein
      ligand interactions showed that Hb possesses evolutionarily conserved surface
      cationic patches that could function as potential LPS-binding sites. Synthetic Hb
      peptides harboring predicted LPS-binding sites served to validate the
      computational predictions. Surface plasmon resonance analysis differentiated LPS
      binding peptides from non-binders. Binding of the peptides to lipid A was further
      substantiated by a fluorescent probe displacement assay. The LPS-binding peptides
      effectively neutralized the endotoxicity of LPS in vitro. Additionally, peptide
      B59 spanning residues 59-95 of Hbbeta attached to the surface of Gram-negative
      bacteria as shown by flow cytometry and visualized by immunogold-labeled scanning
      electron microscopy. Site-directed mutagenesis of the Hb subunits further
      confirmed the function of the predicted residues in binding to LPS. In summary,
      the integration of computational predictions and biophysical characterization has
      enabled delineation of multiple LPS-binding hot spots on the Hb molecule.

PMID- 21900233
TI  - Structural switching of Staphylococcus aureus Clp protease: a key to
      understanding protease dynamics.
AB  - ATP-dependent Clp protease (ClpP) is an attractive new target for the development
      of anti-infective agents. The ClpP protease consists of two heptameric rings that
      enclose a large chamber containing 14 proteolytic active sites. Recent studies
      indicate that ClpP likely undergoes conformational switching between an extended
      and degraded active state required for substrate proteolysis and a compacted and
      catalytically inactive state allowing product release. Here, we present the wild
      type ClpP structures in two distinct states from Staphylococcus aureus. One
      structure is very similar to those solved ClpP structures in the extended states.
      The other is strikingly different from both the extended and the compacted state
      as observed in ClpP from other species; the handle domain of this structure kinks
      to take on a compressed conformation. Structural analysis and molecular dynamic
      simulations show that the handle domain predominantly controls the way in which
      degradation products exit the chamber through dynamic conformational switching
      from the extended state to the compressed state. Given the highly conserved
      sequences among ClpP from different species, this compressed conformation is
      unexpected and novel, which is potentially valuable for understanding the
      enzymatic dynamics and the acting mechanisms of ClpP.

PMID- 21900234
TI  - Amyloid-beta-induced synapse damage is mediated via cross-linkage of cellular
      prion proteins.
AB  - The cellular prion protein (PrP(C)), which is highly expressed at synapses, was
      identified as a receptor for the amyloid-beta (Abeta) oligomers that are
      associated with dementia in Alzheimer disease. Here, we report that Abeta
      oligomers secreted by 7PA2 cells caused synapse damage in cultured neurons via a
      PrP(C)-dependent process. Exogenous PrP(C) added to Prnp knock-out((0/0)) neurons
      was targeted to synapses and significantly increased Abeta-induced synapse
      damage. In contrast, the synapse damage induced by a phospholipase A(2)
      activating peptide was independent of PrP(C). In Prnp wild-type((+/+)) neurons
      Abeta oligomers activated synaptic cytoplasmic phospholipase A(2) (cPLA(2)). In
      these cells, the addition of Abeta oligomers triggered the translocation of
      cPLA(2) in synapses to cholesterol dense membranes (lipid rafts) where it formed
      a complex also containing Abeta and PrP(C). In contrast, the addition of Abeta to
      Prnp((0/0)) neurons did not activate synaptic cPLA(2), which remained in the
      cytoplasm and was not associated with Abeta. Filtration assays and non-denaturing
      gels demonstrated that Abeta oligomers cross-link PrP(C). We propose that it is
      the cross-linkage of PrP(C) by Abeta oligomers that triggers abnormal activation
      of cPLA(2) and synapse damage. This hypothesis was supported by our observation
      that monoclonal antibody mediated cross-linkage of PrP(C) also activated synaptic
      cPLA(2) and caused synapse damage.

PMID- 21900236
TI  - Role of zinc metallothionein-3 (ZnMt3) in epidermal growth factor (EGF)-induced c
      Abl protein activation and actin polymerization in cultured astrocytes.
AB  - Recent evidence indicates that zinc plays a major role in neurochemistry. Of the
      many zinc-binding proteins, metallothionein-3 (Mt3) is regarded as one of the
      major regulators of cellular zinc in the brain. However, biological functions of
      Mt3 are not yet well characterized. Recently, we found that lysosomal dysfunction
      in metallothionein-3 (Mt3)-null astrocytes involves down-regulation of c-Abl. In
      this study, we investigated the role of Mt3 in c-Abl activation and actin
      polymerization in cultured astrocytes following treatment with epidermal growth
      factor (EGF). Compared with wild-type (WT) astrocytes, Mt3-null cells exhibited a
      substantial reduction in the activation of c-Abl upon treatment with EGF.
      Consistent with previous studies, activation of c-Abl by EGF induced dissociation
      of c-Abl from F-actin. Mt3 added to astrocytic cell lysates bound F-actin,
      augmented F-actin polymerization, and promoted the dissociation of c-Abl from F
      actin, suggesting a possible role for Mt3 in this process. Conversely, Mt3
      deficient astrocytes showed significantly reduced dissociation of c-Abl from F
      actin following EGF treatment. Experiments using various peptide fragments of Mt3
      showed that a fragment containing the N-terminal TCPCP motif (peptide 1) is
      sufficient for this effect. Removal of zinc from Mt3 or pep1 with tetrakis(2
      pyridylmethyl)ethylenediamine abrogated the effect of Mt3 on the association of c
      Abl and F-actin, indicating that zinc binding is necessary for this action. These
      results suggest that ZnMt3 in cultured astrocytes may be a normal component of c
      Abl activation in EGF receptor signaling. Hence, modulation of Mt3 levels or
      distribution may prove to be a useful strategy for controlling cytoskeletal
      mobilization following EGF stimulation in brain cells.

PMID- 21900235
TI  - Dual pathways for copper uptake by methanotrophic bacteria.
AB  - Methanobactin (Mb), a 1217-Da copper chelator produced by the methanotroph
      Methylosinus trichosporium OB3b, is hypothesized to mediate copper acquisition
      from the environment, particularly from insoluble copper mineral sources.
      Although indirect evidence suggests that Mb provides copper for the regulation
      and activity of methane monooxygenase enzymes, experimental data for direct
      uptake of copper loaded Mb (Cu-Mb) are lacking. Uptake of intact Cu-Mb by M.
      trichosporium OB3b was demonstrated by isotopic and fluorescent labeling
      experiments. Confocal microscopy data indicate that Cu-Mb is localized in the
      cytoplasm. Both Cu-Mb and unchelated Cu are taken up by M. trichosporium OB3b,
      but by different mechanisms. Uptake of unchelated Cu is inhibited by spermine,
      suggesting a porin-dependent passive transport process. By contrast, uptake of Cu
      Mb is inhibited by the uncoupling agents carbonyl cyanide m-chlorophenylhydrazone
      and methylamine, but not by spermine, consistent with an active transport
      process. Cu-Mb from M. trichosporium OB3b can also be internalized by other
      strains of methanotroph, but not by Escherichia coli, suggesting that Cu-Mb
      uptake is specific to methanotrophic bacteria. These findings are consistent with
      a key role for Cu-Mb in copper acquisition by methanotrophs and have important
      implications for further investigation of the copper uptake machinery.

PMID- 21900237
TI  - CDK1-mediated phosphorylation of Abi1 attenuates Bcr-Abl-induced F-actin assembly
      and tyrosine phosphorylation of WAVE complex during mitosis.
AB  - Coordinated actin remodeling is crucial for cell entry into mitosis. The WAVE
      regulatory complex is a key regulator of actin assembly, yet how the WAVE
      signaling is regulated to coordinate actin assembly with mitotic entry is not
      clear. Here, we have uncovered a novel mechanism that regulates the WAVE complex
      at the onset of mitosis. We found that the Bcr-Abl-stimulated F-actin assembly is
      abrogated during mitosis. This mitotic inhibition of F-actin assembly is
      accompanied by an attenuation of Bcr-Abl-induced tyrosine phosphorylation of the
      WAVE complex. We identified serine 216 of Abi1 as a target of CDK1/cyclin B
      kinase that is phosphorylated in cells at the onset of mitosis. The Abi1
      phosphorylated on serine 216 displayed greatly reduced tyrosine phosphorylation
      in the hematopoietic cells transformed by Bcr-Abl. Moreover, a phosphomimetic
      mutation of serine 216 to aspartic acid in Abi1 was sufficient to attenuate Bcr
      Abl-induced tyrosine phosphorylation of the WAVE complex and F-actin assembly.
      Ectopic expression of Abi1 with serine 216 mutations interfered with cell cycle
      progression. Together, these data show that CDK1-mediated phosphorylation of
      serine 216 in Abi1 serves as a regulatory mechanism that may contribute to
      coordinated actin cytoskeleton remodeling during mitosis.

PMID- 21900238
TI  - Stepwise adaptations to low temperature as revealed by multiple mutants of
      psychrophilic alpha-amylase from Antarctic Bacterium.
AB  - The mutants Mut5 and Mut5CC from a psychrophilic alpha-amylase bear
      representative stabilizing interactions found in the heat-stable porcine
      pancreatic alpha-amylase but lacking in the cold-active enzyme from an Antarctic
      bacterium. From an evolutionary perspective, these mutants can be regarded as
      structural intermediates between the psychrophilic and the mesophilic enzymes. We
      found that these engineered interactions improve all the investigated parameters
      related to protein stability as follows: compactness; kinetically driven
      stability; thermodynamic stability; resistance toward chemical denaturation, and
      the kinetics of unfolding/refolding. Concomitantly to this improved stability,
      both mutants have lost the kinetic optimization to low temperature activity
      displayed by the parent psychrophilic enzyme. These results provide strong
      experimental support to the hypothesis assuming that the disappearance of
      stabilizing interactions in psychrophilic enzymes increases the amplitude of
      concerted motions required by catalysis and the dynamics of active site residues
      at low temperature, leading to a higher activity.

PMID- 21900239
TI  - High throughput short interfering RNA (siRNA) screening of the human kinome
      identifies novel kinases controlling the canonical nuclear factor-kappaB (NF
      kappaB) activation pathway.
AB  - Nuclear factor-kappaB (NF-kappaB) is an inducible cytoplasmic transcription
      factor that plays a role as a master regulator of airway mucosal inflammation.
      The prototypical ("canonical") NF-kappaB pathway controls cytoplasmic to nuclear
      translocation in response to stimulation by the mononuclear cytokine, TNF.
      Despite intensive investigation, the spectrum of kinases involved in the
      canonical NF-kappaB pathway has not yet been systematically determined. Here we
      have applied a high throughput siRNA-mediated loss-of-function screening assay to
      identify novel kinases important in TNF-induced NF-kappaB signaling. Type II A549
      epithelial cells stably expressing an IL-8/luciferase reporter gene optimized for
      high throughput siRNA format (Z' score of 0.65) and siRNAs for 636 human kinases
      were reverse-transfected and screened in the assay. 36 candidate genes were
      identified that inhibited TNF signaling with a Z score deviation of <-1.3 in
      replicate plates. From this group, 11 kinases were selected for independent
      validation, of which eight were successfully silenced. Six kinases were
      validated, including ATM, CDK2, -5, and -7, CALM3, MAPAKP5, and MAP3K/MEKK3. The
      surprising function of ATM in TNF signaling was confirmed where reduced NF
      kappaB/RelA translocation and Ser-276 phosphorylation were seen in ATM(-/-) mouse
      embryo fibroblasts. These data indicate that ATM is a key regulatory kinase that
      may control global NF-kappaB activation in the TNF-induced canonical pathway.

PMID- 21900240
TI  - Stalk domain of the dynamin-like MxA GTPase protein mediates membrane binding and
      liposome tubulation via the unstructured L4 loop.
AB  - The human MxA protein is an interferon-induced large GTPase with antiviral
      activity against a wide range of viruses, including influenza viruses. Recent
      structural data demonstrated that MxA oligomerizes into multimeric filamentous or
      ring-like structures by virtue of its stalk domain. Here, we show that negatively
      charged lipid membranes support MxA self-assembly. Like dynamin, MxA assembled
      around spherical liposomes inducing liposome tubulation. Cryo-transmission
      electron microscopy revealed that MxA oligomers around liposomes have a "T-bar"
      shape similar to dynamin. Moreover, biochemical assays indicated that the
      unstructured L4 loop of the MxA stalk serves as the lipid-binding moiety, and
      mutational analysis of L4 revealed that a stretch of four lysine residues is
      critical for binding. The orientation of the MxA molecule within the membrane
      associated oligomer is in agreement with the proposed topology of MxA oligomers
      based on crystallographic data. Although oligomerization of wild-type MxA around
      liposomes led to the creation of helically decorated tubes similar to those
      formed by dynamin, this lipid interaction did not stimulate GTPase activity, in
      sharp contrast to the assembly-stimulated nucleotide hydrolysis observed with
      dynamin. Moreover, MxA readily self-assembles into rings at physiological
      conditions, as opposed to dynamin which self-assembles only at low salt
      conditions or onto lipids. Thus, the present results indicate that the oligomeric
      structures formed by MxA critically differ from those of dynamin.

PMID- 21900241
TI  - Mechanism of proton transfer in [FeFe]-hydrogenase from Clostridium pasteurianum.
AB  - [FeFe]-Hydrogenases are complex metalloproteins that catalyze the reversible
      reduction of protons to molecular hydrogen utilizing a unique diiron subcluster
      bridged to a [4Fe4S] subcluster. Extensive studies have concentrated on the
      nature and catalytic activity of the active site, yet relatively little
      information is available concerning the mechanism of proton transport that is
      required for this activity. Previously, structural characterization of [FeFe]
      hydrogenase from Clostridium pasteurianum indicated a potential proton transport
      pathway involving four residues (Cys-299, Glu-279, Ser-319, and Glu-282) that
      connect the active site to the enzyme surface. Here, we demonstrate that
      substitution of any of these residues resulted in a drastic reduction in
      hydrogenase activity relative to the native enzyme, supporting the importance of
      these residues in catalysis. Inhibition studies of native and amino acid
      substituted enzymes revealed that Zn(2+) specifically blocked proton transfer by
      binding to Glu-282, confirming the role of this residue in the identified
      pathway. In addition, all four of these residues are strictly conserved,
      suggesting that they may form a proton transport pathway that is common to all
      [FeFe]-hydrogenases.

PMID- 21900242
TI  - Conformational dynamics of wild-type Lys-48-linked diubiquitin in solution.
AB  - Proteasomal degradation is mediated through modification of target proteins by
      Lys-48-linked polyubiquitin (polyUb) chain, which interacts with several binding
      partners in this pathway through hydrophobic surfaces on individual Ub units.
      However, the previously reported crystal structures of Lys-48-linked diUb exhibit
      a closed conformation with sequestered hydrophobic surfaces. NMR studies on
      mutated Lys-48-linked diUb indicated a pH-dependent conformational equilibrium
      between closed and open states with the predominance of the former under neutral
      conditions (90% at pH 6.8). To address the question of how Ub-binding proteins
      can efficiently access the sequestered hydrophobic surfaces of Ub chains, we
      revisited the conformational dynamics of Lys-48-linked diUb in solution using
      wild-type diUb and cyclic forms of diUb in which the Ub units are connected
      through two Lys-48-mediated isopeptide bonds. Our newly determined crystal
      structure of wild-type diUb showed an open conformation, whereas NMR analyses of
      cyclic Lys-48-linked diUb in solution revealed that its structure resembled the
      closed conformation observed in previous crystal structures. Comparison of a
      chemical shift of wild-type diUb with that of monomeric Ub and cyclic diUb, which
      mimic the open and closed states, respectively, with regard to the exposure of
      hydrophobic surfaces to the solvent indicates that wild-type Lys-48-linked diUb
      in solution predominantly exhibits the open conformation (75% at pH 7.0), which
      becomes more populated upon lowering pH. The intrinsic properties of Lys-48
      linked Ub chains to adopt the open conformation may be advantageous for
      interacting with Ub-binding proteins.

PMID- 21900243
TI  - Functional extension of amino acid triads from the fourth transmembrane segment
      (S4) into its external linker in Shaker K(+) channels.
AB  - The highly conserved fourth transmembrane segment (S4) is the primary voltage
      sensor of the voltage-dependent channel and would move outward upon membrane
      depolarization. S4 comprises repetitive amino acid triads, each containing one
      basic (presumably charged and voltage-sensing) followed by two hydrophobic
      residues. We showed that the triad organization is functionally extended into the
      S3-4 linker right external to S4 in Shaker K(+) channels. The arginine (and
      lysine) substitutes for the third and the sixth residues (Ala-359 and Met-356,
      respectively) external to the outmost basic residue (Arg-362) in S4 dramatically
      and additively stabilize S4 in the resting conformation. Also, Leu-361 and Leu
      358 play a very similar role in stabilization of S4 in the resting position,
      presumably by their hydrophobic side chains. Moreover, the double mutation
      A359R/E283A leads to a partially extruded position of S4 and consequently
      prominent closed-state inactivation, suggesting that Glu-283 in S2 may coordinate
      with the arginines in the extruded S4 upon depolarization. We conclude that the
      triad organization extends into the S3-4 linker for about six amino acids in
      terms of their microenvironment. These approximately six residues should retain
      the same helical structure as S4, and their microenvironment serves as part of
      the "gating canal" accommodating the extruding S4. Upon depolarization, S4 most
      likely moves initially as a sliding helix and follows the path that is set by the
      approximately six residues in the S3-4 linker in the resting state, whereas
      further S4 translocation could be more like, for example, a paddle, without
      orderly coordination from the contiguous surroundings.

PMID- 21900244
TI  - Neural precursor cell-expressed developmentally down-regulated protein 4-2 (Nedd4
      2) regulation by 14-3-3 protein binding at canonical serum and glucocorticoid
      kinase 1 (SGK1) phosphorylation sites.
AB  - Regulation of epithelial Na(+) channel (ENaC)-mediated transport in the distal
      nephron is a critical determinant of blood pressure in humans. Aldosterone via
      serum and glucocorticoid kinase 1 (SGK1) stimulates ENaC by phosphorylation of
      the E3 ubiquitin ligase Nedd4-2, which induces interaction with 14-3-3 proteins.
      However, the mechanisms of SGK1- and 14-3-3-mediated regulation of Nedd4-2 are
      unclear. There are three canonical SGK1 target sites on Nedd4-2 that overlap
      phosphorylation-dependent 14-3-3 interaction motifs. Two of these are termed
      "minor," and one is termed "major," based on weak or strong binding to 14-3-3
      proteins, respectively. By mass spectrometry, we found that aldosterone
      significantly stimulates phosphorylation of a minor, relative to the major, 14-3
      3 binding site on Nedd4-2. Phosphorylation-deficient minor site Nedd4-2 mutants
      bound less 14-3-3 than did wild-type (WT) Nedd4-2, and minor site Nedd4-2
      mutations were sufficient to inhibit SGK1 stimulation of ENaC cell surface
      expression. As measured by pulse-chase and cycloheximide chase assays, a major
      binding site Nedd4-2 mutant had a shorter cellular half-life than WT Nedd4-2, but
      this property was not dependent on binding to 14-3-3. Additionally, a
      dimerization-deficient 14-3-3epsilon mutant failed to bind Nedd4-2. We conclude
      that whereas phosphorylation at the Nedd4-2 major site is important for
      interaction with 14-3-3 dimers, minor site phosphorylation by SGK1 may be the
      relevant molecular switch that stabilizes Nedd4-2 interaction with 14-3-3 and
      thus promotes ENaC cell surface expression. We also propose that major site
      phosphorylation promotes cellular Nedd4-2 protein stability, which potentially
      represents a novel form of regulation for turnover of E3 ubiquitin ligases.

PMID- 21900245
TI  - Paxillin enables attachment-independent tyrosine phosphorylation of focal
      adhesion kinase and transformation by RAS.
AB  - Paxillin and HIC5 are closely related adapter proteins that regulate cell
      migration and are tyrosine-phosphorylated by focal adhesion kinase (FAK).
      Paxillin, HIC5, and FAK tyrosine phosphorylation increase upon cell attachment
      and decrease upon detachment from extracellular matrix. Unexpectedly, we found
      that although FAK tyrosine phosphorylation in attached cells did not require
      paxillin, in detached fibroblasts there was remaining FAK tyrosine
      phosphorylation that required expression of paxillin and was not supported by
      HIC5. The support of attachment-independent FAK tyrosine phosphorylation required
      the paxillin LIM domains and suggested that paxillin might facilitate oncogenic
      transformation. Paxillin but not HIC5 augmented anchorage-independent cell
      proliferation induced by RAS. Both anchorage-independent FAK tyrosine
      phosphorylation and RAS-induced colony formation required multiple docking sites
      on paxillin, including LD4 (docking sites for FAK-Src and GIT1/2-PIX-NCK-PAK
      complex), LD5, and all four carboxyl-terminal LIM domains (that bind tubulin and
      PTP-PEST). Analysis using paxillin mutants dissociated domains of paxillin that
      are required for regulation of cell migration from domains that are required for
      anchorage-independent cell proliferation and demonstrated essential functions of
      the paxillin LIM domains that are not found in HIC5 LIM domains. These results
      highlight the role of paxillin in facilitating attachment-independent signal
      transduction implicated in cancer.

PMID- 21900246
TI  - Chemical structure of Trichomonas vaginalis surface lipoglycan: a role for short
      galactose (beta1-4/3) N-acetylglucosamine repeats in host cell interaction.
AB  - The extracellular parasite Trichomonas vaginalis contains a surface
      glycoconjugate that appears to mediate parasite-host cell interaction via binding
      to human galectin-1. This glycoconjugate also elicits cytokine production from
      human vaginal epithelial cells, implicating its role in modulation of host immune
      responses. We have analyzed the structure of this glycoconjugate, previously
      described to contain the sugars rhamnose (Rha), N-acetylglucosamine (GlcNAc),
      galactose (Gal), xylose (Xyl), N-acetylgalactosamine (GalNAc), and glucose (Glc),
      using gas chromatograph mass spectrometry (GC-MS), matrix-assisted laser
      desorption/ionization time of flight mass spectrometry (MALDI-TOF), electrospray
      MS/MS, and nuclear magnetic resonance (NMR), combined with chemical and enzymatic
      digestions. Our data reveal a complex structure, named T. vaginalis lipoglycan
      (TvLG), that differs markedly from Leishmania lipophosphoglycan and Entamoeba
      lipopeptidophosphoglycan and is devoid of phosphosaccharide repeats. TvLG is
      composed of an alpha1-3 linked polyrhamnose core, where Rha residues are
      substituted at the 2-position with either beta-Xyl or chains of, on average, five
      N-acetyllactosamine (-3Galbeta1-4GlcNAcbeta1-) (LacNAc) units and occasionally
      lacto-N-biose (-3Galbeta1-3GlcNAcbeta1-) (LNB). These chains are themselves
      periodically substituted at the Gal residues with Xyl-Rha. These structural
      analyses led us to test the role of the poly-LacNAc/LNB chains in parasite
      binding to host cells. We found that reduction of poly-LacNAc/LNB chains
      decreased the ability of TvLG to compete parasite binding to host cells. In
      summary, our data provide a new model for the structure of TvLG, composed of a
      polyrhamnose backbone with branches of Xyl and poly-LacNAc/LNB. Furthermore, the
      poly-LacNAc side chains are shown to be involved in parasite-host cell
      interaction.

PMID- 21900247
TI  - Identification of self-lipids presented by CD1c and CD1d proteins.
AB  - The CD1 family consists of five proteins that are related to the peptide
      presenting MHC class I family. T cells can recognize the presentation of both
      foreign and self-derived lipids on four CD1 family members. The identities of the
      self-lipids capable of stimulating autoreactive T cell responses remain elusive
      or controversial. Here, we employed mass spectrometry to analyze the lipid
      content of highly purified CD1c and CD1d protein samples. We report the
      identification of 11 novel self-lipids presented by CD1c and nine by CD1d.
      Rigorous controls provide strong evidence that the identified lipids were
      specifically loaded into the lipid-binding site of the CD1 molecules. The diverse
      but distinct population of lipids identified from each CD1 family member implies
      each present a different subset of self-lipids, and the enrichment of particular
      motifs indicates that the lipids that are presented by CD1 family members could
      be predicted. Finally, our results imply the CD1 system surveys the endoplasmic
      reticulum, Golgi apparatus, and/or secretory compartments, in addition to its
      well characterized surveillance of the endocytic and lysosomal compartments.

PMID- 21900248
TI  - Interaction with monomeric subunit c drives insertion of ATP synthase subunit a
      into the membrane and primes a-c complex formation.
AB  - Subunit a is the main part of the membrane stator of the ATP synthase molecular
      turbine. Subunit c is the building block of the membrane rotor. We have generated
      two molecular fusions of a and c subunits with different orientations of the
      helical hairpin of subunit c. The a/c fusion protein with correct orientation of
      transmembrane helices was inserted into the membrane, and co-incorporated into
      the F(0) complex of ATP synthase with wild type subunit c. The fused c subunit
      was incorporated into the c-ring tethering the ATP synthase rotor to the stator.
      The a/c fusion with incorrect orientation of the c-helices required wild type
      subunit c for insertion into the membrane. In this case, the fused c subunit
      remained on the periphery of the c-ring and did not interfere with rotor
      movement. Wild type subunit a inserted into the membrane equally well with wild
      type subunit c and c-ring assembly mutants that remained monomeric in the
      membrane. These results show that interaction with monomeric subunit c triggers
      insertion of subunit a into the membrane, and initiates formation of the a-c
      complex, the ion-translocating module of the ATP synthase. Correct assembly of
      the ATP synthase incorporating topologically correct fusion of subunits a and c
      validates using this model protein for high resolution structural studies of the
      ATP synthase proton channel.

PMID- 21900249
TI  - Aging neural progenitor cells have decreased mitochondrial content and lower
      oxidative metabolism.
AB  - Although neurogenesis occurs in discrete areas of the adult mammalian brain,
      neural progenitor cells (NPCs) produce fewer new neurons with age. To
      characterize the molecular changes that occur during aging, we performed a
      proteomic comparison between primary-cultured NPCs from the young adult and aged
      mouse forebrain. This analysis yielded changes in proteins necessary for cellular
      metabolism. Mitochondrial quantity and oxygen consumption rates decrease with
      aging, although mitochondrial DNA in aged NPCs does not have increased mutation
      rates. In addition, aged cells are resistant to the mitochondrial inhibitor
      rotenone and proliferate in response to lowered oxygen conditions. These results
      demonstrate that aging NPCs display an altered metabolic phenotype, characterized
      by a coordinated shift in protein expression, subcellular structure, and
      metabolic physiology.

PMID- 21900250
TI  - The RhoG/ELMO1/Dock180 signaling module is required for spine morphogenesis in
      hippocampal neurons.
AB  - Dendritic spines are actin-rich structures, the formation and plasticity of which
      are regulated by the Rho GTPases in response to synaptic input. Although several
      guanine nucleotide exchange factors (GEFs) have been implicated in spine
      development and plasticity in hippocampal neurons, it is not known how many
      different Rho GEFs contribute to spine morphogenesis or how they coordinate the
      initiation, establishment, and maintenance of spines. In this study, we screened
      70 rat Rho GEFs in cultured hippocampal neurons by RNA interference and
      identified a number of candidates that affected spine morphogenesis. Of these,
      Dock180, which plays a pivotal role in a variety of cellular processes including
      cell migration and phagocytosis, was further investigated. We show that depletion
      of Dock180 inhibits spine morphogenesis, whereas overexpression of Dock180
      promotes spine morphogenesis. ELMO1, a protein necessary for in vivo functions of
      Dock180, functions in a complex with Dock180 in spine morphogenesis through
      activating the Rac GTPase. Moreover, RhoG, which functions upstream of the
      ELMO1/Dock180 complex, is also important for spine formation. Together, our
      findings uncover a role for the RhoG/ELMO1/Dock180 signaling module in spine
      morphogenesis in hippocampal neurons.

PMID- 21900251
TI  - Trefoil factor 2 requires Na/H exchanger 2 activity to enhance mouse gastric
      epithelial repair.
AB  - Trefoil factor (TFF) peptides are pivotal for gastric restitution after surface
      epithelial damage, but TFF cellular targets that promote cell migration are
      poorly understood. Conversely, Na/H exchangers (NHE) are often implicated in
      cellular migration but have a controversial role in gastric restitution. Using
      intravital microscopy to create microscopic lesions in the mouse gastric surface
      epithelium and directly measure epithelial restitution, we evaluated whether TFFs
      and NHE isoforms share a common pathway to promote epithelial repair. Blocking
      Na/H exchange (luminal 10 MUm 5-(N-ethyl-N-isopropyl) amiloride or 25 MUm HOE694)
      slows restitution 72-83% in wild-type or NHE1(-/-) mice. In contrast, HOE694 has
      no effect on the intrinsically defective gastric restitution in NHE2(-/-) mice or
      TFF2(-/-) mice. In TFF2(-/-) mice, NHE2 protein is reduced 23%, NHE2 remains
      localized to apical membranes of surface epithelium, and NHE1 protein amount or
      localization is unchanged. The action of topical rat TFF3 to accelerate
      restitution in TFF2(-/-) mice was inhibited by AMD3100 (CXCR4 receptor
      antagonist). Furthermore, rat TFF3 did not rescue restitution when NHE2 was
      inhibited [TFF2(-/-) mice +HOE694, or NHE2(-/-) mice]. HOE694 had no effect on pH
      at the juxtamucosal surface before or after damage. We conclude that functional
      NHE2, but not NHE1, is essential for mouse gastric epithelial restitution and
      that TFFs activate epithelial repair via NHE2.

PMID- 21900252
TI  - Copper alters aggregation behavior of prion protein and induces novel
      interactions between its N- and C-terminal regions.
AB  - Copper is reported to promote and prevent aggregation of prion protein.
      Conformational and functional consequences of Cu(2+)-binding to prion protein
      (PrP) are not well understood largely because most of the Cu(2+)-binding studies
      have been performed on fragments and truncated variants of the prion protein. In
      this context, we set out to investigate the conformational consequences of Cu(2+)
      binding to full-length prion protein (PrP) by isothermal calorimetry, NMR, and
      small angle x-ray scattering. In this study, we report altered aggregation
      behavior of full-length PrP upon binding to Cu(2+). At physiological temperature,
      Cu(2+) did not promote aggregation suggesting that Cu(2+) may not play a role in
      the aggregation of PrP at physiological temperature (37  degrees C). However,
      Cu(2+)-bound PrP aggregated at lower temperatures. This temperature-dependent
      process is reversible. Our results show two novel intra-protein interactions upon
      Cu(2+)-binding. The N-terminal region (residues 90-120 that contain the site His
      96/His-111) becomes proximal to helix-1 (residues 144-147) and its nearby loop
      region (residues 139-143), which may be important in preventing amyloid fibril
      formation in the presence of Cu(2+). In addition, we observed another novel
      interaction between the N-terminal region comprising the octapeptide repeats
      (residues 60-91) and helix-2 (residues 174-185) of PrP. Small angle x-ray
      scattering studies of full-length PrP show significant compactness upon Cu(2+)
      binding. Our results demonstrate novel long range inter-domain interactions of
      the N- and C-terminal regions of PrP upon Cu(2+)-binding, which might have
      physiological significance.

PMID- 21900253
TI  - Polymeric structure and host Toll-like receptor 4 dictate immunogenicity of NY
      ESO-1 antigen in vivo.
AB  - In search of intrinsic factors that contribute to the distinctively strong
      immunogenicity of a non-mutated cancer/testis antigen, we found that NY-ESO-1
      forms polymeric structures through disulfide bonds. NY-ESO-1 binding to immature
      dendritic cells was dependent on its polymeric structure and involved Toll-like
      receptor-4 (TLR4) on the surface of immature dendritic cells in mouse and human.
      Gene gun-delivered plasmid encoding the wild-type NY-ESO-1 readily induced T cell
      dependent antibody (Ab) responses in wild-type C57BL/10 mice but not TLR4-knock
      out C57BL/10ScNJ mice. Disrupting polymeric structures of NY-ESO-1 by cysteine-to
      serine (Cys-to-Ser) substitutions lead to diminished immunogenicity and altered
      TLR4-dependence in the induced Ab response. To demonstrate its adjuvant effect,
      NY-ESO-1 was fused with a major mugwort pollen allergen Art v 1 and a tumor
      associated antigen, carbonic anhydrase 9. Plasmid DNA vaccines encoding the
      fusion genes generated robust immune responses against otherwise non-immunogenic
      targets in mice. Polymeric structure and TLR4 may play important roles in
      rendering NY-ESO-1 immunogenic and thus serve as a potent molecular adjuvant. NY
      ESO-1 thus represents the first example of a cancer/testis antigen that is a also
      damage-associated molecular pattern.

PMID- 21900256
TI  - Floral closure induced by pollination in gynodioecious Cyananthus delavayi
      (Campanulaceae): effects of pollen load and type, floral morph and fitness
      consequences.
AB  - BACKGROUND AND AIMS: Pollination-induced floral changes, which have been widely
      documented in flowering plants, have been assumed to enhance the plant's
      reproductive success. However, our understanding of the causes and consequences
      of these changes is still limited. Using an alpine gynodioecious species,
      Cyananthus delavayi, we investigated the factors affecting floral closure and
      estimated the fitness consequences of floral closure. METHODS: The timings of
      floral closure and fertilization were determined. The effects of pollen load,
      pollen type (cross- or self-pollen) and floral morph (female or perfect flower)
      on the occurrence of floral closure were examined. Ovule fertilization and seed
      production were examined to investigate the causes and consequences of floral
      closure. Flowers were manipulated to prevent closing to detect potential benefits
      for female fitness. KEY RESULTS: Floral closure, which could be induced by a very
      low pollen load, occurred within 4-7 h after pollination, immediately following
      fertilization. The proportion of closed flowers was influenced by pollen load and
      floral morph, but not by pollen type. Floral closure was more likely to occur in
      flowers with a higher proportion of fertilized ovules, but there was no
      significant difference in seed production between closed and open flowers. Those
      flowers in which closure was induced by natural pollination had low fruit set and
      seed production. Additionally, seed production was not influenced by closing
      prevented manipulation when sufficient pollen deposition was received.
      CONCLUSIONS: The occurrence of floral closure may be determined by the proportion
      of fertilized ovules, but this response can be too sensitive to ensure sufficient
      pollen deposition and can, to some extent, lead to a cost in female fitness.
      These results implied that the control of floral receptivity by the recipient
      flowers does not lead to an optimal fitness gain in C. delavayi.

PMID- 21900254
TI  - T cell activation by terminal complex of complement and immune complexes.
AB  - T cell hyperactivation and complement consumption are prominent features of the
      immunopathology of systemic lupus erythematosus. Although complement activation
      is secondary to autoantibodies that form immune complexes (ICs), the trigger for
      alterations in human peripheral blood T cells is poorly understood. To study the
      impact (on T cells) of several types of preformed ICs and terminal complement
      complex, also referred to as C5b-9, we incubated these immune reactants with
      peripheral blood naive CD4(+) T cells as well as Jurkat cells and analyzed their
      effects on cellular behavior. We first assembled the C5b-9 in situ on the
      membrane and observed its assembly primarily on a single site where it promoted
      aggregation of membrane rafts and recruitment of the CD3 signaling complex.
      However, C5b-9 alone did not initiate proliferation or commencement of downstream
      signaling events associated with T cell activation. When T cells were treated
      with ICs together with nonlytic C5b-9, changes associated with T cell activation
      by possible antigen engagement then occurred. T cell antigen receptor signaling
      proteins, including zeta-chain, ZAP-70, Syk, Src, and Lck, were phosphorylated
      and organized in a synapse-like structure. The cytoskeleton formed F-actin
      spindles and a distal pole complex, resulting in a bipolar distribution of
      phosphorylated ezrin-radixin-moesin and F-actin. Furthermore, ICs and nonlytic
      C5b-9 induced T cell proliferation and IFN-gamma production. These results raise
      the possibility that ICs and the nonlytic C5b-9 modulate T cell-mediated
      responses in systemic lupus erythematosus and other related chronic inflammatory
      disorders.

PMID- 21900257
TI  - The diabetic amputation lottery.

PMID- 21900255
TI  - Expanded CUG repeats Dysregulate RNA splicing by altering the stoichiometry of
      the muscleblind 1 complex.
AB  - To understand the role of the splice regulator muscleblind 1 (MBNL1) in the
      development of RNA splice defects in myotonic dystrophy I (DM1), we purified RNA
      independent MBNL1 complexes from normal human myoblasts and examined the behavior
      of these complexes in DM1 myoblasts. Antibodies recognizing MBNL1 variants
      (MBNL1(CUG)), which can sequester in the toxic CUG RNA foci that develop in DM1
      nuclei, were used to purify MBNL1(CUG) complexes from normal myoblasts. In normal
      myoblasts, MBNL1(CUG) bind 10 proteins involved in remodeling ribonucleoprotein
      complexes including hnRNP H, H2, H3, F, A2/B1, K, L, DDX5, DDX17, and DHX9. Of
      these proteins, only MBNL1(CUG) colocalizes extensively with DM1 CUG foci (>80%
      of foci) with its partners being present in <10% of foci. Importantly, the
      stoichiometry of MBNL1(CUG) complexes is altered in DM1 myoblasts, demonstrating
      an increase in the steady state levels of nine of its partner proteins. These
      changes are recapitulated by the expression of expanded CUG repeat RNA in Cos7
      cells. Altered stoichiometry of MBNL1(CUG) complexes results from aberrant
      protein synthesis or stability and is unlinked to PKCalpha function. Modeling
      these changes in normal myoblasts demonstrates that increased levels of hnRNP H,
      H2, H3, F, and DDX5 independently dysregulate splicing in overlapping RNA
      subsets. Thus expression of expanded CUG repeats alters the stoichiometry of
      MBNL1(CUG) complexes to allow both the reinforcement and expansion of RNA
      processing defects.

PMID- 21900258
TI  - Laparoscopic cholecystectomy under field conditions in Asiatic black bears (Ursus
      thibetanus) rescued from illegal bile farming in Vietnam.
AB  - Nine adult Asiatic black bears (Ursus thibetanus) previously rescued from illegal
      bile farming in Vietnam were examined via abdominal ultrasound and exploratory
      laparoscopy for liver and gall bladder pathology. Three bears demonstrated
      notable gall bladder pathology, and minimally invasive cholecystectomies were
      performed using an open laparoscopic access approach, standard 10 to 12 mmHg
      carbon dioxide pneumoperitoneum and a four-port technique. A single bear required
      insertion of an additional 5 mm port and use of a flexible liver retractor due to
      the presence of extensive adhesions between the gall bladder and quadrate and
      left and right medial liver lobes. The cystic duct was dissected free and this
      and the cystic artery were ligated by means of extracorporeal tied Meltzer knot
      sutures. The gall bladder was dissected free of the liver by blunt and sharp
      dissection, aided by 3.8 MHz monopolar radiosurgery. Bears that have had open
      abdominal cholecystectomies are reported as taking four to six weeks before a
      return to normal activity postoperatively. In contrast, these bears demonstrated
      rapid unremarkable healing, and were allowed unrestricted access to outside
      enclosures to climb trees, swim and interact normally with other bears within
      seven days of surgery.

PMID- 21900259
TI  - Echinococcus multilocularis in an imported captive European beaver (Castor fiber)
      in Great Britain.

PMID- 21900260
TI  - Dorsolateral spinal cord compression at the C2-C3 junction in two Cavalier King
      Charles spaniels.

PMID- 21900261
TI  - Prevalence of Coxiella burnetii in livestock abortion material using PCR.

PMID- 21900262
TI  - Evidence that purifying selection acts on promoter sequences.
AB  - We tested whether functionally important sites in bacterial, yeast, and animal
      promoters are more conserved than their neighbors. We found that substitutions
      are predominantly seen in less important sites and that those that occurred
      tended to have less impact on gene expression than possible alternatives. These
      results suggest that purifying selection operates on promoter sequences.

PMID- 21900263
TI  - Genetic architecture of male sterility and segregation distortion in Drosophila
      pseudoobscura Bogota-USA hybrids.
AB  - Understanding the genetic basis of reproductive isolation between recently
      diverged species is a central problem in evolutionary genetics. Here, I present
      analyses of the genetic architecture underlying hybrid male sterility and
      segregation distortion between the Bogota and USA subspecies of Drosophila
      pseudoobscura. Previously, a single gene, Overdrive (Ovd), was shown to be
      necessary but not sufficient for both male sterility and segregation distortion
      in F(1) hybrids between these subspecies, requiring several interacting partner
      loci for full manifestation of hybrid phenomena. I map these partner loci
      separately on the Bogota X chromosome and USA autosomes using a combination of
      different mapping strategies. I find that hybrid sterility involves a single
      hybrid incompatibility of at least seven interacting partner genes that includes
      three large-effect loci. Segregation distortion involves three loci on the Bogota
      X chromosome and one locus on the autosomes. The genetic bases of hybrid
      sterility and segregation distortion are at least partially--but not completely-
      overlapping. My results lay the foundation for fine-mapping experiments to
      identify the complete set of genes that interact with Overdrive. While individual
      genes that cause hybrid sterility or inviability have been identified in a few
      cases, my analysis provides a comprehensive look at the genetic architecture of
      all components of a hybrid incompatibility underlying F(1) hybrid sterility. Such
      an analysis would likely be unfeasible for most species pairs due to their
      divergence time and emphasizes the importance of young species pairs such as the
      D. pseudoobscura subspecies studied here.

PMID- 21900264
TI  - Interfering waves of adaptation promote spatial mixing.
AB  - A fundamental problem of asexual adaptation is that beneficial substitutions are
      not efficiently accumulated in large populations: Beneficial mutations often go
      extinct because they compete with one another in going to fixation. It has been
      argued that such clonal interference may have led to the evolution of sex and
      recombination in well-mixed populations. Here, we study clonal interference, and
      mechanisms of its mitigation, in an evolutionary model of spatially structured
      populations with uniform selection pressure. Clonal interference is much more
      prevalent with spatial structure than without, due to the slow wave-like spread
      of beneficial mutations through space. We find that the adaptation speed of
      asexuals saturates when the linear habitat size exceeds a characteristic
      interference length, which becomes shorter with smaller migration and larger
      mutation rate. The limiting speed is proportional to MU(1/2) and MU(1/3) in
      linear and planar habitats, respectively, where the mutational supply MU is the
      product of mutation rate and local population density. This scaling and the
      existence of a speed limit should be amenable to experimental tests as they fall
      far below predicted adaptation speeds for well-mixed populations (that scale as
      the logarithm of population size). Finally, we show that not only recombination,
      but also long-range migration is a highly efficient mechanism of relaxing clonal
      competition in structured populations. Our conservative estimates of the
      interference length predict prevalent clonal interference in microbial colonies
      and biofilms, so clonal competition should be a strong driver of both genetic and
      spatial mixing in those contexts.

PMID- 21900265
TI  - Genomically biased accumulation of seed storage proteins in allopolyploid cotton.
AB  - Allopolyploidy is an important process during plant evolution that results in the
      reunion of two divergent genomes into a common nucleus. Many of the immediate as
      well as longer-term genomic and epigenetic responses to polyploidy have become
      appreciated. To investigate the modifications of gene expression at the proteome
      level caused by allopolyploid formation, we conducted a comparative analysis of
      cotton seed proteomes from the allopolyploid Gossypium hirsutum (AD genome) and
      its model A-genome and D-genome diploid progenitors. An unexpectedly high level
      of divergence among the three proteomes was found, with about one-third of all
      protein forms being genome specific. Comparative analysis showed that there is a
      higher degree of proteomic similarity between the allopolyploid and its D-genome
      donor than its A-genome donor, reflecting a biased accumulation of seed proteins
      in the allopolyploid. Protein identification and genetic characterization of high
      abundance proteins revealed that two classes of seed storage proteins, vicilins
      and legumins, compose the major component of cotton seed proteomes. Analyses
      further indicate differential regulation or modification of homoeologous gene
      products, as well as novel patterns in the polyploid proteome that may result
      from the interaction between homoeologous gene products. Our findings demonstrate
      that genomic merger and doubling have consequences that extend beyond the
      transcriptome into the realm of the proteome and that unequal expression of
      proteins from diploid parental genomes may occur in allopolyploids.

PMID- 21900266
TI  - A general method for calculating likelihoods under the coalescent process.
AB  - Analysis of genomic data requires an efficient way to calculate likelihoods
      across very large numbers of loci. We describe a general method for finding the
      distribution of genealogies: we allow migration between demes, splitting of demes
      [as in the isolation-with-migration (IM) model], and recombination between linked
      loci. These processes are described by a set of linear recursions for the
      generating function of branch lengths. Under the infinite-sites model, the
      probability of any configuration of mutations can be found by differentiating
      this generating function. Such calculations are feasible for small numbers of
      sampled genomes: as an example, we show how the generating function can be
      derived explicitly for three genes under the two-deme IM model. This derivation
      is done automatically, using Mathematica. Given data from a large number of
      unlinked and nonrecombining blocks of sequence, these results can be used to find
      maximum-likelihood estimates of model parameters by tabulating the probabilities
      of all relevant mutational configurations and then multiplying across loci. The
      feasibility of the method is demonstrated by applying it to simulated data and to
      a data set previously analyzed by Wang and Hey (2010) consisting of 26,141 loci
      sampled from Drosophila simulans and D. melanogaster. Our results suggest that
      such likelihood calculations are scalable to genomic data as long as the numbers
      of sampled individuals and mutations per sequence block are small.

PMID- 21900267
TI  - Isoform-specific regulation of a steroid hormone nuclear receptor by an E3
      ubiquitin ligase in Drosophila melanogaster.
AB  - The steroid hormone 20-hydroxyecdysone (20E) regulates gene transcription through
      the heterodimeric nuclear receptor composed of ecdysone receptor (EcR) and
      Ultraspiracle (USP). The EcR gene encodes three protein isoforms--A, B1, and B2-
      with variant N-terminal domains that mediate tissue and developmental stage
      specific responses to 20E. Ariadne-1a is a conserved member of the RING finger
      family of ubiquitin ligases first identified in Drosophila melanogaster. Loss-of
      function mutations at key cysteines in either of the two RING finger motifs, as
      well as general overexpression of this enzyme, cause lethality in pupae, which
      suggests a requirement in metamorphosis. Here, we show that Ariadne-1a binds
      specifically the isoform A of EcR and ubiquitylates it. Co-immunoprecipitation
      experiments indicate that the full sequence of EcRA is required for this binding.
      Protein levels of EcRA and USP change in opposite directions when those of ARI-1a
      are genetically altered. This is an isoform-specific, E3-dependent regulatory
      mechanism for a steroid nuclear receptor. Further, qRT-PCR experiments show that
      the ARI-1a levels lead to the transcriptional regulation of Eip78C, Eip74EF,
      Eip75B, and Br-C, as well as that of EcR and usp genes. Thus, the activity of
      this enzyme results in the regulation of dimerizing receptors at the protein and
      gene transcription levels. This fine-tuned orchestration by a conserved ubiquitin
      ligase is required during insect metamorphosis and, likely, in other steroid
      hormone-controlled processes across species.

PMID- 21900269
TI  - The population genetics of X-autosome synthetic lethals and steriles.
AB  - Epistatic interactions are widespread, and many of these interactions involve
      combinations of alleles at different loci that are deleterious when present in
      the same individual. The average genetic environment of sex-linked genes differs
      from that of autosomal genes, suggesting that the population genetics of
      interacting X-linked and autosomal alleles may be complex. Using both analytical
      theory and computer simulations, we analyzed the evolutionary trajectories and
      mutation-selection balance conditions for X-autosome synthetic lethals and
      steriles. Allele frequencies follow a set of fundamental trajectories, and
      incompatible alleles are able to segregate at much higher frequencies than single
      locus expectations. Equilibria exist, and they can involve fixation of either
      autosomal or X-linked alleles. The exact equilibrium depends on whether synthetic
      alleles are dominant or recessive and whether fitness effects are seen in males,
      females, or both sexes. When single-locus fitness effects and synthetic
      incompatibilities are both present, population dynamics depend on the dominance
      of alleles and historical contingency (i.e., whether X-linked or autosomal
      mutations occur first). Recessive synthetic lethality can result in high
      frequency X-linked alleles, and dominant synthetic lethality can result in high
      frequency autosomal alleles. Many X-autosome incompatibilities in natural
      populations may be cryptic, appearing to be single-locus effects because one
      locus is fixed. We also discuss the implications of these findings with respect
      to standing genetic variation and the origins of Haldane's rule.

PMID- 21900268
TI  - The Drosophila CPEB protein Orb2 has a novel expression pattern and is important
      for asymmetric cell division and nervous system function.
AB  - Cytoplasmic polyadenylation element binding (CPEB) proteins bind mRNAs to
      regulate their localization and translation. While the first CPEBs discovered
      were germline specific, subsequent studies indicate that CPEBs also function in
      many somatic tissues including the nervous system. Drosophila has two CPEB family
      members. One of these, orb, plays a key role in the establishment of polarity
      axes in the developing egg and early embryo, but has no known somatic functions
      or expression outside of the germline. Here we characterize the other Drosophila
      CPEB, orb2. Unlike orb, orb2 mRNA and protein are found throughout development in
      many different somatic tissues. While orb2 mRNA and protein of maternal origin
      are distributed uniformly in early embryos, this pattern changes as development
      proceeds and by midembryogenesis the highest levels are found in the CNS and PNS.
      In the embryonic CNS, Orb2 appears to be concentrated in cell bodies and mostly
      absent from the longitudinal and commissural axon tracts. In contrast, in the
      adult brain, the protein is seen in axonal and dendritic terminals. Lethal
      effects are observed for both RNAi knockdowns and orb2 mutant alleles while
      surviving adults display locomotion and behavioral defects. We also show that
      orb2 funtions in asymmetric division of stem cells and precursor cells during the
      development of the embryonic nervous system and mesoderm.

PMID- 21900270
TI  - Nonclassical regulation of transcription: interchromosomal interactions at the
      malic enzyme locus of Drosophila melanogaster.
AB  - Regulation of transcription can be a complex process in which many cis- and trans
      interactions determine the final pattern of expression. Among these interactions
      are trans-interactions mediated by the pairing of homologous chromosomes. These
      trans-effects are wide ranging, affecting gene regulation in many species and
      creating complex possibilities in gene regulation. Here we describe a novel case
      of trans-interaction between alleles of the Malic enzyme (Men) locus in
      Drosophila melanogaster that results in allele-specific, non-additive gene
      expression. Using both empirical biochemical and predictive bioinformatic
      approaches, we show that the regulatory elements of one allele are capable of
      interacting in trans with, and modifying the expression of, the second allele.
      Furthermore, we show that nonlocal factors--different genetic backgrounds--are
      capable of significant interactions with individual Men alleles, suggesting that
      these trans-effects can be modified by both locally and distantly acting
      elements. In sum, these results emphasize the complexity of gene regulation and
      the need to understand both small- and large-scale interactions as more complete
      models of the role of trans-interactions in gene regulation are developed.

PMID- 21900271
TI  - Genetic dissection of salicylic acid-mediated defense signaling networks in
      Arabidopsis.
AB  - Properly coordinated defense signaling networks are critical for the fitness of
      plants. One hub of the defense networks is centered on salicylic acid (SA), which
      plays a key role in activating disease resistance in plants. However, while a
      number of genes are known to affect SA-mediated defense, relatively little is
      known about how these gene interact genetically with each other. Here we
      exploited the unique defense-sensitized Arabidopsis mutant accelerated cell death
      (acd) 6-1 to dissect functional relationships among key components in the SA hub.
      We show that while enhanced disease susceptibility (eds) 1-2 and phytoalexin
      deficient (pad) 4-1 suppressed acd6-1-conferred small size, cell death, and
      defense phenotypes, a combination of these two mutations did not incur additive
      suppression. This suggests that EDS1 and PAD4 act in the same signaling pathway.
      To further evaluate genetic interactions among SA regulators, we constructed 10
      pairwise crosses in the acd6-1 background among mutants defective in: SA
      INDUCTION-DEFICIENT 2 for SA biosynthesis; AGD2-LIKE DEFENSE 1, EDS5, and PAD4
      for SA accumulation; and NONEXPRESSOR OF PR GENES 1 for SA signaling. Systematic
      analysis of the triple mutants based on their suppression of acd6-1-conferred
      phenotypes revealed complex and interactive genetic relationships among the
      tested SA genes. Our results suggest a more comprehensive view of the gene
      networks governing SA function and provide a framework for further interrogation
      of the important roles of SA and possibly other signaling molecules in regulating
      plant disease resistance.

PMID- 21900272
TI  - Distinguishing driver and passenger mutations in an evolutionary history
      categorized by interference.
AB  - In many biological scenarios, from the development of drug resistance in
      pathogens to the progression of healthy cells toward cancer, quantifying the
      selection acting on observed mutations is a central question. One difficulty in
      answering this question is the complexity of the background upon which mutations
      can arise, with multiple potential interactions between genetic loci. We here
      present a method for discerning selection from a population history that accounts
      for interference between mutations. Given sequences sampled from multiple time
      points in the history of a population, we infer selection at each locus by
      maximizing a likelihood function derived from a multilocus evolution model. We
      apply the method to the question of distinguishing between loci where new
      mutations are under positive selection (drivers) and loci that emit neutral
      mutations (passengers) in a Wright-Fisher model of evolution. Relative to an
      otherwise equivalent method in which the genetic background of mutations was
      ignored, our method inferred selection coefficients more accurately for both
      driver mutations evolving under clonal interference and passenger mutations
      reaching fixation in the population through genetic drift or hitchhiking. In a
      population history recorded by 750 sets of sequences of 100 individuals taken at
      intervals of 100 generations, a set of 50 loci were divided into drivers and
      passengers with a mean accuracy of >0.95 across a range of numbers of driver
      loci. The potential application of our model, either in full or in part, to a
      range of biological systems, is discussed.

PMID- 21900273
TI  - Nuclear structure and chromosome segregation in Drosophila male meiosis depend on
      the ubiquitin ligase dTopors.
AB  - In many organisms, homolog pairing and synapsis at meiotic prophase depend on
      interactions between chromosomes and the nuclear membrane. Male Drosophila lack
      synapsis, but nonetheless, their chromosomes closely associate with the nuclear
      periphery at prophase I. To explore the functional significance of this
      association, we characterize mutations in nuclear blebber (nbl), a gene required
      for both spermatocyte nuclear shape and meiotic chromosome transmission. We
      demonstrate that nbl corresponds to dtopors, the Drosophila homolog of the
      mammalian dual ubiquitin/small ubiquitin-related modifier (SUMO) ligase Topors.
      We show that mutations in dtopors cause abnormalities in lamin localizations,
      centriole separation, and prophase I chromatin condensation and also cause
      anaphase I bridges that likely result from unresolved homolog connections. Bridge
      formation does not require mod(mdg4) in meiosis, suggesting that bridges do not
      result from misregulation of the male homolog conjunction complex. At the
      ultrastructural level, we observe disruption of nuclear shape, an uneven
      perinuclear space, and excess membranous structures. We show that dTopors
      localizes to the nuclear lamina at prophase, and also transiently to intranuclear
      foci. As a role of dtopors at gypsy insulator has been reported, we also asked
      whether these new alleles affected expression of the gypsy-induced mutation ct(6)
      and found that it was unaltered in dtopors homozygotes. Our results indicate that
      dTopors is required for germline nuclear structure and meiotic chromosome
      segregation, but in contrast, is not necessary for gypsy insulator function. We
      suggest that dtopors plays a structural role in spermatocyte lamina that is
      critical for multiple aspects of meiotic chromosome transmission.

PMID- 21900275
TI  - Multiple adaptive substitutions during evolution in novel environments.
AB  - We consider an asexual population under strong selection-weak mutation conditions
      evolving on rugged fitness landscapes with many local fitness peaks. Unlike the
      previous studies in which the initial fitness of the population is assumed to be
      high, here we start the adaptation process with a low fitness corresponding to a
      population in a stressful novel environment. For generic fitness distributions,
      using an analytic argument we find that the average number of steps to a local
      optimum varies logarithmically with the genotype sequence length and increases as
      the correlations among genotypic fitnesses increase. When the fitnesses are
      exponentially or uniformly distributed, using an evolution equation for the
      distribution of population fitness, we analytically calculate the fitness
      distribution of fixed beneficial mutations and the walk length distribution.

PMID- 21900277
TI  - 'Gastric bronchus' associated with a congenital bronchopulmonary malformation.

PMID- 21900274
TI  - Rapid mapping and identification of mutations in Caenorhabditis elegans by
      restriction site-associated DNA mapping and genomic interval pull-down
      sequencing.
AB  - Forward genetic screens provide a powerful approach for inferring gene function
      on the basis of the phenotypes associated with mutated genes. However,
      determining the causal mutation by traditional mapping and candidate gene
      sequencing is often the rate-limiting step, especially when analyzing many
      mutants. We report two genomic approaches for more rapidly determining the
      identity of the affected genes in Caenorhabditis elegans mutants. First, we
      report our use of restriction site-associated DNA (RAD) polymorphism markers for
      rapidly mapping mutations after chemical mutagenesis and mutant isolation.
      Second, we describe our use of genomic interval pull-down sequencing (GIPS) to
      selectively capture and sequence megabase-sized portions of a mutant genome.
      Together, these two methods provide a rapid and cost-effective approach for
      positional cloning of C. elegans mutant loci, and are also applicable to other
      genetic model systems.

PMID- 21900278
TI  - Initial improvements in apnoea-hypopnoea index after very low calorie diet
      maintained for 1 year with weight loss maintenance program.

PMID- 21900279
TI  - Shifts with nurse understaffing and high patient churn linked to heightened
      inpatient mortality risk in a single site study.

PMID- 21900280
TI  - Prediction of survival without morbidity for infants born at under 33 weeks
      gestational age: a user-friendly graphical tool.
AB  - OBJECTIVE: To develop models and a graphical tool for predicting survival to
      discharge without major morbidity for infants with a gestational age (GA) at
      birth of 22-32 weeks using infant information at birth. DESIGN: Retrospective
      cohort study. SETTING: Canadian Neonatal Network data for 2003-2008 were
      utilised. PATIENTS: Neonates born between 22 and 32 weeks gestation admitted to
      neonatal intensive care units in Canada. MAIN OUTCOME MEASURE: Survival to
      discharge without major morbidity defined as survival without severe neurological
      injury (intraventricular haemorrhage grade 3 or 4 or periventricular
      leukomalacia), severe retinopathy (stage 3 or higher), necrotising enterocolitis
      (stage 2 or 3) or chronic lung disease. RESULTS: Of the 17 148 neonates who met
      the eligibility criteria, 65% survived without major morbidity. Sex and GA at
      birth were significant predictors. Birth weight (BW) had a significant but non
      linear effect on survival without major morbidity. Although maternal information
      characteristics such as steroid use, improved the prediction of survival without
      major morbidity, sex, GA at birth and BW for GA predicted survival without major
      morbidity almost as accurately (area under the curve: 0.84). The graphical tool
      based on the models showed how the GA and BW for GA interact, to enable
      prediction of outcomes especially for small and large for GA infants. CONCLUSION:
      This graphical tool provides an improved and easily interpretable method to
      predict survival without major morbidity for very preterm infants at the time of
      birth. These curves are especially useful for small and large for GA infants.

PMID- 21900281
TI  - Distribution of natural and anthropogenic radionuclides in heavy rainfall areas
      in Jordan.
AB  - Soil is the main reservoir of both natural and artificial radionuclides, which
      are transported to the human body through the food chain. Thus, assessment of the
      level of radioactivity in soil is of crucial importance. Artificial radionuclide
      concentrations in soil depend heavily on rainfall and weather conditions. In this
      study, the soil of the Ras Muneef area, which has the highest rainfall in Jordan,
      was investigated for its natural and anthropogenic radioactive content. The area
      was divided into four sectors and in each sector three locations were
      investigated depending on the land use: undisturbed, cultivated or residential.
      The depth profile of (137)Cs was investigated and found to depend on the land
      use. In the undisturbed soils, two types of depth profiles were identified:
      Gaussian and exponentially decreasing. The annual effective dose was found to
      range from 19.4 to 72.6 MUSv, which falls within the worldwide ranges.

PMID- 21900282
TI  - Human leucocyte antigen risk alleles for psoriatic arthritis among patients with
      psoriasis.
AB  - Aim Genes that differentiate patients with psoriatic arthritis (PsA) from those
      with cutaneous psoriasis (PsC) may serve as markers for the development of PsA in
      patients with psoriasis. The authors aimed to identify human leucocyte antigen
      (HLA) alleles that are associated with the development of PsA in patients with
      psoriasis. METHODS: 712 adult patients with PsA, 335 adult patients with PsC and
      713 healthy controls were genotyped for HLA-A, HLA-B, HLA-C, HLA-DR and HLA-DQ
      alleles. Differences in allelic distributions for each of the HLA loci were
      compared using a likelihood ratio test. Logistic regression analysis of multiple
      loci was performed to account for linkage disequilibrium. Haplotype information
      was inferred using the expectation-maximisation algorithm (given HLA-C and HLA-B
      genotypes) and analysed similarly. RESULTS: The following HLA alleles were found
      to be significantly associated with patients with PsA compared to patients with
      PsC in multivariate regression analysis: B*08 (OR 1.61, p=0.009), B*27 (OR 5.17,
      p<0.0001), B*38 (OR 1.65, p=0.026) and C*06 (OR 0.58, p=0.0002). HLA-B*27, HLA
      B*38 and HLA-C*06 frequencies were also significantly higher in patients with PsA
      than in healthy controls (B*27: OR 3.05, p<0.0001; B*38: OR 5.9, p<0.0001; HLA
      C*06: OR 1.71, p<0.0001). The following haplotypes were independently associated
      with PsA compared to PsC: HLA-B*18-C*07 (OR 10.1, p=0.004), HLA-B*27-C*01 (OR
      41.1, p<0.0001), HLA-B*27-C*02 (OR 19.9, p<0.0001), HLA-B*38-C*12 (OR 2.9,
      p=0.01), HLA-B*08-C*07 (OR 2.6, p=0.004) and HLA-B*57-C*06 (OR 0.5, p=0.03).
      CONCLUSIONS: Certain HLA-B and HLA-C alleles confer susceptibility to PsA among
      patients with psoriasis and may be used to identify patients with PsC who may
      develop PsA.

PMID- 21900283
TI  - Assessment and determinants of aesthetic discomfort in hand osteoarthritis.
AB  - BACKGROUND: Dissatisfaction with hand appearance is frequently the presenting
      complaint of patients with hand osteoarthritis (HOA), yet no tool exists for its
      measurement and few studies have examined aesthetic discomfort. OBJECTIVES: The
      aims of this study were to measure the extent and to explore the associations of
      aesthetic concerns in HOA. METHODS: 172 patients with HOA were assessed with
      tender joint and node count, global and pain scores, Functional Index for Hand
      Osteoarthritis, Short Form-12, Hospital Anxiety and Depression Scale and
      posterior-anterior hand radiographs. Patients scored the aesthetic impact of the
      disease on a Visual Analogue Scale of 0-100 mm and were classified into low,
      intermediate and high aesthetic concern (HAC) based on this score. RESULTS: Of
      172 patients (155 women), the majority (92%) had nodes and 46% had erosive
      disease. The mean aesthetic score was 44.8 mm (SD 35.9), and 59 (34.3%) patients
      scored their aesthetic discomfort >= 66 mm. Factors associated with HAC were
      female gender, a high number of tender joints and nodes, high global and pain
      scores, high radiological damage scores, the presence of erosions and high
      depression and anxiety levels. The multivariate analysis identified two
      independent factors associated with HAC: patient's global assessment (p=0.0005)
      and radiographic erosions (p=0.03). CONCLUSIONS: Aesthetic discomfort is a major
      concern for a significant number of patients with HOA, particularly women, those
      with a high burden of HOA disease and those with erosive osteoarthritis, and is
      also associated with depression, anxiety and poor health-related quality of life.

PMID- 21900284
TI  - Validation of the ASAS criteria and definition of a positive MRI of the
      sacroiliac joint in an inception cohort of axial spondyloarthritis followed up
      for 8 years.
AB  - BACKGROUND: The new Assessment of SpondyloArthritis international Society (ASAS)
      criteria classify axial spondyloarthritis (SpA) into human leucocyte antigen-B27
      and/or imaging-based arms. To aid implementation, ASAS has proposed a definition
      of a positive MRI for active sacroiliitis. OBJECTIVE: The authors aimed to test
      the diagnostic and predictive value of the ASAS criteria and definition of a
      'positive' MRI. METHODS: Baseline MRI scans on 29 patients with early
      inflammatory back pain and 18 controls were read independently by four
      experienced rheumatologists. Both arms of the criteria were tested against a
      'gold standard' of physician diagnosis of SpA. MRI abnormalities were assessed
      according to a global assessment of MRI and the ASAS definition. Sensitivity,
      specificity and likelihood ratios for individual and concordant reader data were
      calculated for axial SpA diagnosis at baseline and the development of
      radiographic sacroiliitis, fulfilling the modified New York criteria at 8 years.
      RESULTS: All patients were classified as having axial SpA, with more patients
      fulfilling the imaging arm (83%, n=24/29) than the human leucocyte antigen B27
      arm (62%, n=18/29). Concordant reader data showed that the baseline MRI had high
      diagnostic utility for SpA according to global assessment
      (sensitivity/specificity: 66%/94%, LR+ (positive likelihood ratio) 11.8, LR-
      (negative likelihood ratio) 0.4) and ASAS definition (sensitivity/specificity:
      79%/89%, LR+ 7.1, LR- 0.2). Likewise, a positive baseline MRI had 100%
      sensitivity for subsequent radiographic sacroiliitis by either assessment,
      although specificity was lower (56% for global assessment and 33% for ASAS
      definition). CONCLUSION: Both arms of the ASAS criteria have good diagnostic
      utility in early SpA, although they are of limited value for the prediction of
      radiographic progression. This may be due to the definition of a positive MRI for
      sacroiliitis that lacks specificity at baseline.

PMID- 21900285
TI  - Risk of thromboembolic events after recurrent spontaneous abortion in
      antiphospholipid syndrome: a case-control study.
AB  - OBJECTIVE: To investigate whether patients having antiphospholipid syndrome (APS)
      as the only aetiological factor for recurrent spontaneous abortion (RSA) are at
      increased risk of thrombosis later in life. METHODS: A case-control study at a
      tertiary university referral centre. The study group consisted of 57 primary APS
      and RSA women (APS-RSA group). Control groups included: 86 patients with RSA of
      unknown aetiology (uRSA group), 42 patients with RSA and thrombophilic genetic
      defects as the only aetiologic factor for RSA (tRSA group) and 30
      antiphospholipid antibody (aPL) positive but otherwise healthy women (aPL group).
      The main measurement was the thrombosis rate after long-term follow-up. RESULTS:
      APS-RSA patients had a significantly higher 12-year cumulative thrombotic
      incidence rate compared with the three comparator groups (19.3% vs 4.8%, 0.0% and
      0.0%, respectively (log rank), p<0.001). Patients in the APS-RSA group had 25.6
      thrombotic events per 1000 patient-years (95% CI 12.8 to 45.9). The OR of
      thrombosis in relation to the presence (APS-RSA group) or absence (uRSA and tRSA
      groups) of aPL in patients with RSA was 15.06 (95% CI 3.2 to 70.5). CONCLUSIONS:
      Our data indicate that a history of RSA associated with aPL is a risk factor for
      subsequent thrombosis in the long term.

PMID- 21900286
TI  - Regulating the regulators: SOCS3 joins the dance.

PMID- 21900287
TI  - Low circulating Dickkopf-1 and its link with severity of spinal involvement in
      diffuse idiopathic skeletal hyperostosis.
AB  - OBJECTIVE: Dickkopf-1 (DKK-1) is an inhibitor of osteoblastogenesis, and its
      lower levels are linked to new bone formation. The aim of this study was
      therefore to explore serum levels of DKK-1 and to evaluate DKK-1's association
      with the severity of spinal involvement in diffuse idiopathic skeletal
      hyperostosis (DISH). METHODS: Serum levels of total and functional DKK-1 and C
      reactive protein (CRP) were measured in 37 patients with DISH and 22 healthy age
      and sex-matched controls. Plain radiographs of the cervical and thoracic spine
      were performed, and the diagnosis of DISH was defined using the Resnick criteria.
      Patients were divided into three groups based on spinal involvement. Bone mineral
      density (BMD) and bone turnover markers were evaluated in patients with DISH.
      RESULTS: The levels of total serum DKK-1 were significantly lower in patients
      with DISH than in healthy controls (p<0.0001). Importantly, low serum levels of
      DKK-1 were associated with more severe spinal involvement in DISH, independent of
      age, sex, disease duration, CRP, bone turnover markers or BMD. However, these
      findings were less significant for functional DKK-1. CONCLUSION: These
      observations indicate that DKK-1 may play a significant role in bone formation
      during DISH.

PMID- 21900288
TI  - Children in Beardslee's family intervention: relieved by understanding of
      parental mental illness.
AB  - BACKGROUND: Beardslee's family intervention (FI), which is a family-based
      preventive method for children of mentally ill parents, has been implemented on a
      national level in Sweden. MATERIAL: Fourteen children and parents from nine
      families were interviewed about how the FI was for the children. Data were
      analysed by qualitative content analysis. DISCUSSION: A central finding was
      children's sense of relief and release from worry because of more knowledge and
      openness about the parent's illness in the family. CONCLUSION: The results
      indicating relief for the children are encouraging.

PMID- 21900289
TI  - The win ratio: a new approach to the analysis of composite endpoints in clinical
      trials based on clinical priorities.
AB  - The conventional reporting of composite endpoints in clinical trials has an
      inherent limitation in that it emphasizes each patient's first event, which is
      often the outcome of lesser clinical importance. To overcome this problem, we
      introduce the concept of the win ratio for reporting composite endpoints.
      Patients in the new treatment and control groups are formed into matched pairs
      based on their risk profiles. Consider a primary composite endpoint, e.g.
      cardiovascular (CV) death and heart failure hospitalization (HF hosp) in heart
      failure trials. For each matched pair, the new treatment patient is labelled a
      'winner' or a 'loser' depending on who had a CV death first. If that is not
      known, only then they are labelled a 'winner' or 'loser' depending on who had a
      HF hosp first. Otherwise they are considered tied. The win ratio is the total
      number of winners divided by the total numbers of losers. A 95% confidence
      interval and P-value for the win ratio are readily obtained. If formation of
      matched pairs is impractical then an alternative win ratio can be obtained by
      comparing all possible unmatched pairs. This method is illustrated by re-analyses
      of the EMPHASIS-HF, PARTNER B, and CHARM trials. The win ratio is a new method
      for reporting composite endpoints, which is easy to use and gives appropriate
      priority to the more clinically important event, e.g. mortality. We encourage its
      use in future trial reports.

PMID- 21900291
TI  - Cardiac calciphylaxis presenting as endocarditis.

PMID- 21900290
TI  - Genetic variants, plasma lipoprotein(a) levels, and risk of cardiovascular
      morbidity and mortality among two prospective cohorts of type 2 diabetes.
AB  - AIMS: To examine the relations between genetic loci, plasma lipoprotein(a)
      [Lp(a)] levels, and cardiovascular disease (CVD) risk among diabetic patients and
      compare with the observations in the general population. METHODS AND RESULTS: In
      two prospective cohorts of patients with type 2 diabetes (n= 2308) from the
      Nurses' Health Study and the Health Professional Follow-Up Study, we performed
      (i) genome-wide association (GWA) scans for plasma Lp(a); (ii) prospective
      analysis of plasma Lp(a) for CVD risk and mortality; and (iii) genetic
      association analysis for CVD risk and mortality. Meta-analysis of the two GWA
      scans yielded 71 single-nucleotide polymorphisms (SNPs) on chromosome 6q
      associated with plasma Lp(a) levels at a genome-wide significance level (P< 5 *
      10(-8)). The SNP rs10455872 in LPA was most strongly associated with Lp(a) (P=
      4.60 * 10(-39)). Forward-selection analysis indicated that rs10455872 and other
      five SNPs in a region encompassing LPA, PLG, SLC22A3, and LPAL2 genes were
      independently associated with Lp(a) levels and jointly explained ~20% of
      variation in diabetic patients. In prospective analysis, we did not find any
      significant association between plasma levels and CVD incidence; the relative
      risk for coronary heart disease (CHD), CVD, and CVD death was 1.05 [95%
      confidence interval (CI): 0.95-1.15], 1.05 (0.96-1.15), and 1.21 (0.99-1.47) per
      1-SD higher log-transformed Lp(a) levels, respectively. Consistently, none of the
      Lp(a) SNPs were associated with CVD risk or mortality (all P> 0.09). For the best
      SNP rs10455872 for plasma Lp(a) levels, the OR for CHD, CVD, and CVD death was
      0.94 (95% CI: 0.69-1.28), 0.97 (0.72-1.29), and 1.23 (0.79-1.92), respectively.
      The genetic effect on CHD risk showed a significant heterogeneity between the
      diabetic and the general populations (P= 0.006). CONCLUSION: Our data indicate
      that the effect of Lp(a) on CVD risk among diabetic patients might be different
      from that in the general population. Diabetes status may attenuate the relation
      between Lp(a) and cardiovascular risk.

PMID- 21900292
TI  - Thrombus formation 10 years after placement of an atrial septal secundum defect
      closure device.

PMID- 21900293
TI  - Mortality in heart failure with preserved ejection fraction: an unacceptably high
      rate.

PMID- 21900294
TI  - Transcatheter implantation of an aortic valve prosthesis in a female patient with
      severe bicuspid aortic stenosis.

PMID- 21900295
TI  - Hybrid cardiac magnetic resonance/computed tomographic imaging: first fusion of
      three-dimensional magnetic resonance perfusion and low-dose coronary computed
      tomographic angiography.

PMID- 21900296
TI  - Neurological oxygen toxicity.
AB  - SCUBA diving has several risks associated with it from breathing air under
      pressure--nitrogen narcosis, barotrauma and decompression sickness (the bends).
      Trimix SCUBA diving involves regulating mixtures of nitrogen, oxygen and helium
      in an attempt to overcome the risks of narcosis and decompression sickness during
      deep dives, but introduces other potential hazards such as hypoxia and oxygen
      toxicity convulsions. This study reports on a seizure during the ascent phase,
      its potential causes and management and discusses the hazards posed to the diver
      and his rescuer by an emergency ascent to the surface.

PMID- 21900297
TI  - To resuscitate or not to resuscitate: a logistic regression analysis of physician
      related variables influencing the decision.
AB  - OBJECTIVE: To determine whether variables in physicians' backgrounds influenced
      their decision to forego resuscitating a patient they did not previously know.
      METHODS: Questionnaire survey of a convenience sample of 204 physicians working
      in the departments of internal medicine, anaesthesiology and cardiology in 11
      hospitals in Israel. RESULTS: Twenty per cent of the participants had elected to
      forego resuscitating a patient they did not previously know without additional
      consultation. Physicians who had more frequently elected to forego resuscitation
      had practised medicine for more than 5 years (p=0.013), estimated the number of
      resuscitations they had performed as being higher (p=0.009), and perceived their
      experience in resuscitation as sufficient (p=0.001). The variable that predicted
      the outcome of always performing resuscitation in the logistic regression model
      was less than 5 years of experience in medicine (OR 0.227, 95% CI 0.065 to 0.793;
      p=0.02). CONCLUSION: Physicians' level of experience may affect the probability
      of a patient's receiving resuscitation, whereas the physicians' personal beliefs
      and values did not seem to affect this outcome.

PMID- 21900298
TI  - Feasibility of detecting early left ventricular systolic dysfunction using global
      area strain: a novel index derived from three-dimensional speckle-tracking
      echocardiography.
AB  - AIMS: Area strain (AS), derived from three-dimensional speckle-tracking
      echocardiography (3D-STE), is a novel parameter integrating longitudinal and
      circumferential deformation. We sought to evaluate the ability of global AS to
      detect early left ventricular (LV) systolic dysfunction in patients with risk
      factors for heart failure (HF). METHODS AND RESULTS: Standard echocardiography
      and 3D-STE were performed in 160 subjects with or without HF. Three-dimensional
      speckle-tracking echocardiography was measured with reliable tracking quality in
      137 (86%) of the 160 subjects initially enrolled in this study: 30 healthy
      volunteers, 29, 37, 26, and 15 patients with Stage A, B, C, and D HF,
      respectively. Global strain values were automatically calculated by 3D wall
      motion tracking (3D-WMT) software. Although global longitudinal strain (LS),
      circumferential strain (CS), radial strain (RS), and LV ejection fraction (LVEF)
      showed the downward trend from normal controls to patients with Stage D HF, the
      difference did not reach statistical significance between normal controls and
      patients with Stage A HF. In contrast, we observed the progressive decrease in
      global AS from normal to Stage A HF to Stage D HF (P< 0.05). In addition, global
      AS showed an excellent correlation with LVEF, global LS and CS. The optimal cut
      off value for global AS, to detect LV dysfunction (Simpson's rule-based LVEF
      <50%), was -29.23% at a sensitivity of 86.3% and at a specificity of 88.4%.
      CONCLUSION: Global AS is a sensitive and reproducible parameter to detect early
      and subtle LV systolic dysfunction, showing greater feasibility than other
      conventional strain parameters.

PMID- 21900299
TI  - Symptomatic pericardial cyst: a case series.
AB  - Pericardial cysts are most commonly located at the cardiophrenic angle or,
      rarely, in the posterior or anterior superior mediastinum. The majority of
      pericardial cysts are asymptomatic and are found incidentally. Symptomatic
      pericardial cysts present with dyspnoea, chest pain, or persistent cough. We
      describe four patients with symptomatic pericardial cysts who were treated with
      either echocardiographically guided percutaneous aspiration or video-assisted
      thoracoscopic surgery, or both; thoracotomy; or conservative therapy.

PMID- 21900301
TI  - Anomalous origin of the right coronary artery from the pulmonary artery: a rare
      finding in an asymptomatic man.

PMID- 21900300
TI  - Right ventricular systolic function assessment: rank of echocardiographic methods
      vs. cardiac magnetic resonance imaging.
AB  - AIMS: Right ventricular (RV) systolic function is prognostically important, but
      its assessment by echocardiography remains challenging, in part because of the
      multitude of available measurement methods. The purpose of this prospective study
      was to rank these methods against the reference of RV ejection fraction (EF) as
      obtained in a broad clinical population by magnetic resonance imaging (MRI).
      METHODS AND RESULTS: Two hundred and twenty-three individuals were included in
      the study. The following seven Doppler echocardiographic parameters were tested
      using receiver operating characteristic (ROC) analysis for their accuracy to
      distinguish between normal and moderately impaired RVEF by MRI (RVEF cut-off
      50%), respectively, between moderately and severely reduced RVEF (cut-off 30%):
      RV fractional area and fractional long-axis change (FLC), RV myocardial
      performance index (MPI), tricuspid annular peak systolic excursion, Doppler
      tissue imaging-derived isovolumic acceleration and peak systolic velocity (S') at
      the lateral tricuspid annulus, and strain at the lateral free wall as obtained by
      speckle-tracking echocardiography. Survival analysis was performed. All seven
      Doppler echocardiographic parameters correlated significantly with RVEF by MRI
      (range between 5 and 85%). RVEF <50% was best detected by S' < 11 cm/s: area
      under the ROC curve 0.779 (95% confidence interval 0.716-0.843), sensitivity
      0.740, and specificity 0.753. RVEF <=30% was best detected by MPI > 0.50: area
      under the ROC curve 0.948 (95% confidence interval 0.906-0.991), sensitivity
      0.947, and specificity 0.852. The Kaplan-Meier analysis revealed reduced
      cumulative survival among patients with RVEF <=30% (P = 0.0003). CONCLUSION: A
      systolic long-axis peak velocity of <11 cm/s at the lateral tricuspid annulus
      most accurately detects moderately impaired RVEF as obtained by MRI; severely
      reduced RVEF <=30% is best detected by RV MPI at a value of >0.50.

PMID- 21900302
TI  - Myocardial function may improve equally in diabetic patients following both
      multivessel percutaneous coronary intervention and coronary artery bypass
      grafting: results from a CARDia trial substudy.
AB  - AIMS: The CARDia (Coronary Artery Revascularization in Diabetes) trial compared
      coronary artery bypass grafting (CABG) and optimal percutaneous coronary
      intervention (PCI) in diabetic patients with multivessel coronary disease.
      Patients enrolled had symptoms of myocardial ischaemia. As symptom assessment is
      flawed in diabetic patients, a substudy was undertaken to compare the extent to
      which these revascularization strategies alter reversible ischaemia. METHODS AND
      RESULTS: Seventy-one patients underwent stress echo at baseline and at 6 months.
      A 17-segment echocardiographic wall motion score index (WMSI) was assigned at
      baseline [WMSI(pre)] and at 6 months [WMSI(post)]. An overall score defined the
      difference: WMSI(?) = WMSI(pre)--WMSI(post). Of 71 patients recruited, 42
      underwent PCI and 29 CABG. Mean WMSI(pre) in the PCI group was 1.63 and mean
      WMSI(post) was 1.32. Mean WMSI(pre) in the CABG group was 1.69 and mean
      WMSI(post) was 1.46. The PCI WMSI(?) was 0.31 and CABG WMSI(?) was 0.23 (P =
      0.8). Of 42 PCI patients, 39 demonstrated ischaemia at baseline. At 6 months 31
      had improvements in ischaemia (79%), 5 showed no improvement, and 3 ischaemia
      worsened. Of 29 CABG patients, 23 demonstrated ischaemia at baseline. At 6
      months, 20 had improvements in ischaemia (87%), 2 had no improvement, and in 1
      ischaemia worsened. No difference was seen in the number of patients with
      improvements in reversible ischaemia between PCI and CABG [79 vs. 87%, (P =
      0.9)]. CONCLUSION: Optimal revascularization in diabetic patients with
      multivessel disease remains controversial. This subset analysis of the CARDia
      trial suggests both PCI and CABG achieve similar improvement in reversible
      ischaemia.

PMID- 21900303
TI  - Increasing the thermostability of sucrose phosphorylase by a combination of
      sequence- and structure-based mutagenesis.
AB  - Sucrose phosphorylase is a promising biocatalyst for the glycosylation of a wide
      variety of acceptor molecules, but its low thermostability is a serious drawback
      for industrial applications. In this work, the stability of the enzyme from
      Bifidobacterium adolescentis has been significantly improved by a combination of
      smart and rational mutagenesis. The former consists of substituting the most
      flexible residues with amino acids that occur more frequently at the
      corresponding positions in related sequences, while the latter is based on a
      careful inspection of the enzyme's crystal structure to promote electrostatic
      interactions. In this way, a variant enzyme could be created that contains six
      mutations and whose half-life at the industrially relevant temperature of 60 
      degrees C has more than doubled compared with the wild-type enzyme. An increased
      stability in the presence of organic co-solvents could also be observed, although
      these effects were most noticeable at low temperatures.

PMID- 21900304
TI  - Use of periplasmic target protein capture for phage display engineering of tight
      binding protein-protein interactions.
AB  - Phage display is a powerful tool to study and engineer protein and peptide
      interactions. It is not without its limitations, however, such as the requirement
      for target protein purification and immobilization in a correctly folded state. A
      protein capture method is described here that allows enrichment of tight-binding
      protein variants in vivo thereby eliminating the need for target protein
      purification and immobilization. The linkage of genotype to phenotype is achieved
      by placing both receptor and ligand encoding genes on the same plasmid. This
      allows the isolation of the tight-binding ligand-receptor pair complexes after
      their association in the bacterial periplasm. The interaction between the TEM-1
      beta-lactamase fused to the gene 3 coat protein displayed on the surface of M13
      bacteriophage and the beta-lactamse inhibitory protein (BLIP) expressed in
      soluble form with a signal sequence to export it to the periplasm was used as a
      model system to test the method. The system was experimentally validated using a
      previously characterized collection of BLIP alanine mutants with a range of
      binding affinities for TEM-1 beta-lactamase and by isolating tight-binding
      variants from a library of mutants randomized at residue position Tyr50 in BLIP
      which contacts beta-lactamase.

PMID- 21900306
TI  - Thermostabilization of firefly luciferase by in vivo directed evolution.
AB  - Firefly luciferase is widely used in a number of areas of biotechnology and
      molecular biology. However, rapid inactivation of wild-type (WT) luciferases at
      elevated temperatures often hampers their application. A simple non-lethal in
      vivo screening scheme was used to identify thermostable mutants of luciferase in
      Escherichia coli colonies. This scheme allowed carrying out each cycle of
      mutagenesis in a rapid and efficient manner. Four rounds of directed evolution
      were conducted on a part of the gene coding for amino acid residues 130-390 of
      Luciola mingrelica luciferase. The resultant mutant designated 4TS had a half
      life of 10 h at 42 degrees C, which is 65-fold higher compared with the WT
      luciferase. Moreover, the mutant 4TS showed a 1.9-fold increase in specific
      activity, 5.7-fold reduction of K(m) for ATP and a higher-temperature optimum
      compared with the WT enzyme. 4TS contains eight mutations, four of which are
      suggested to be mainly responsible for the enhancement of thermostability: R211L,
      A217V, E356K and S364C. Thus, directed evolution with non-lethal colony screening
      for in vivo bioluminescence activity proved to be an effective and efficient
      approach for increasing thermal stability of luciferase while retaining high
      catalytic activity.

PMID- 21900305
TI  - An evaluation tool for FKBP12-dependent and -independent mTOR inhibitors using a
      combination of FKBP-mTOR fusion protein, DSC and NMR.
AB  - Mammalian target of rapamycin (mTOR), a large multidomain protein kinase,
      regulates cell growth and metabolism in response to environmental signals. The
      FKBP rapamycin-binding (FRB) domain of mTOR is a validated therapeutic target for
      the development of immunosuppressant and anticancer drugs but is labile and
      insoluble. Here we designed a fusion protein between FKBP12 and the FRB domain of
      mTOR. The fusion protein was successfully expressed in Escherichia coli as a
      soluble form, and was purified by a simple two-step chromatographic procedure.
      The fusion protein exhibited increased solubility and stability compared with the
      isolated FRB domain, and facilitated the analysis of rapamycin and FK506 binding
      using differential scanning calorimetry (DSC) and solution nuclear magnetic
      resonance (NMR). DSC enabled the rapid observation of protein-drug interactions
      at the domain level, while NMR gave insights into the protein-drug interactions
      at the residue level. The use of the FKBP12-FRB fusion protein combined with DSC
      and NMR provides a useful tool for the efficient screening of FKBP12-dependent as
      well as -independent inhibitors of the mTOR FRB domain.

PMID- 21900307
TI  - The effect of question wording in questionnaire surveys on placebo use in
      clinical practice.
AB  - To identify factors that contribute to the high variability of the rates of use
      of placebo interventions reported in questionnaire surveys, the author
      investigated the effect of the explicit use of the word "placebo" in
      questionnaire surveys on placebo use in clinical practice on the results
      obtained. 190 primary care physicians in Poland were divided randomly into two
      groups. The groups received a questionnaire in which either the word placebo or
      the term "nonspecific methods of treatment" was used. The respondents who were
      asked explicitly about the use of placebo interventions declared that they never
      used placebo interventions significantly more often than participants asked about
      the use of nonspecific treatment methods. Moreover, the former reported
      significantly rarer use of placebo interventions than the latter. The study
      demonstrates that differences in the wording of questions in questionnaire
      surveys on placebo use can create statistically significant differences in
      results.

PMID- 21900309
TI  - Sex differences in pain responses at maturity following neonatal repeated minor
      pain exposure in rats.
AB  - There is mounting evidence of long-lasting changes in pain sensitivity in school
      age children who were cared for in a neonatal intensive care unit. Such care
      involves multiple pain exposures, 70% of which are accounted for by heel lance to
      monitor physiological well-being. The authors sought to model the repeated brief
      pain resulting from heel lance by administering repeated paw needle stick to
      neonatal rat pups. Repeated needle stick during the first 8 days of life was sex
      specific in altering responses to mechanical and inflammatory stimuli, but not to
      a thermal stimulus, at maturity. Specifically, neonatal paw needle stick males
      exhibited significantly greater mechanical sensitivity in response to von Frey
      hair testing, whereas neonatal paw needle stick females exhibited significantly
      greater pain behavior scores following hindpaw formalin injection. This is the
      first study to show such sex-dependent changes in pain responsiveness at maturity
      in animals having experienced repeated neonatal needle stick pain. These findings
      support existing evidence that there are long-term sensory sequelae following
      neonatal pain experiences in rats and further suggest that there are sex-linked
      differences in the nature of the consequences. If these relationships hold in
      humans, these findings suggest that even mild painful insults early in life are
      not without sensory consequences.

PMID- 21900308
TI  - A psychoneuroimmunologic examination of cumulative perinatal steroid exposures
      and preterm infant behavioral follow-up.
AB  - PURPOSE: This study's aim was to explore relationships between preterm infant
      behavioral outcomes and maternal/infant glucocorticoid (dexamethasone [DEX])
      treatments using a psychoneuroimmunologic approach. Research questions were (a)
      do relationships exist between infant cumulative perinatal steroid (PNS) exposure
      and child behavioral problems? and (b) do maternal/infant characteristics (e.g.,
      immune markers and biophysiologic stressors) influence these relationships?
      METHODS: The convenience sample comprised 45 mother-child dyads in which the
      children (mean age 8 years +/- 2.3) had been born at a mean postconceptional age
      of 28 weeks (+/- 4.2). We used the Child Behavior Checklist (CBCL) to assess
      behavior, the Clinical Risk Index for Babies (CRIB) to score stress at birth, and
      retrospective record review to identify additional perinatal factors (PNS dosage,
      sepsis, and maternal and infant complete blood counts near delivery). RESULTS:
      Children were dichotomized into high (> 0.2 mg/kg; n = 20) versus low-no (<=0.2
      mg/kg; n = 25) PNS exposure groups. Significant relationships existed between
      CBCL Total Problems score and sepsis, PNS exposure, timing of initial PNS, and
      infant length percentile at discharge. Competence problems were significantly
      associated with PNS, neonatal intensive care unit (NICU) infant length
      percentile, CRIB score, sepsis, retinopathy of prematurity, hearing deficit, and
      immunity markers (i.e., maternal lymphocyte percentage and infant band/seg
      ratio). Children in the higher PNS group exhibited more behavioral problems
      (e.g., withdrawn, attention, conduct, social, and rule breaking problems), but
      there were no significant differences. The findings are reassuring regarding long
      term effects of this PNS dose on preterm infant behavioral outcomes.

PMID- 21900310
TI  - Mid-Cretaceous charred fossil flowers reveal direct observation of arthropod
      feeding strategies.
AB  - Although plant-arthropod relationships underpin the dramatic rise in diversity
      and ecological dominance of flowering plants and their associated arthropods,
      direct observations of such interactions in the fossil record are rare, as these
      ephemeral moments are difficult to preserve. Three-dimensionally preserved
      charred remains of Chloranthistemon flowers from the Late Albian to Early
      Cenomanian of Germany preserve scales of mosquitoes and an oribatid mite with
      mouthparts inserted into the pollen sac. Mosquitoes, which today are frequent
      nectar feeders, and the mite were feeding on pollen at the time wildfire consumed
      the flowers. These findings document directly arthropod feeding strategies and
      their role in decomposition.

PMID- 21900311
TI  - A stab in the dark: chick killing by brood parasitic honeyguides.
AB  - The most virulent avian brood parasites obligately kill host young soon after
      hatching, thus ensuring their monopoly of host parental care. While the host
      eviction behaviour of cuckoos (Cuculidae) is well documented, the host killing
      behaviour of honeyguide (Indicatoridae) chicks has been witnessed only once, 60
      years ago, and never in situ in host nests. Here, we report from the Afrotropical
      greater honeyguide the first detailed observations of honeyguides killing host
      chicks with their specially adapted bill hooks, based on repeated video
      recordings (available in the electronic supplementary material). Adult greater
      honeyguides puncture host eggs when they lay their own, but in about half of host
      nests at least one host egg survived, precipitating chick killing by the
      honeyguide hatchling. Hosts always hatched after honeyguide chicks, and were
      killed within hours. Despite being blind and in total darkness, honeyguides
      attacked host young with sustained biting, grasping and shaking motions. Attack
      time of 1-5 min was sufficient to cause host death, which took from 9 min to over
      7 h from first attack. Honeyguides also bit unhatched eggs and human hands, but
      only rarely bit the host parents feeding them.

PMID- 21900312
TI  - Repeated colonization of remote islands by specialized mutualists.
AB  - Mutualisms are ubiquitous in nature, but constraints imposed by specialization
      may limit their ability to colonize novel environments synchronously. The ability
      of mutualisms to reassemble following disturbance is central to understanding
      their response to global change. Here, we demonstrate that a highly specialized
      pollination mutualism considered to be obligate (Phyllanthaceae: Glochidion;
      Lepidoptera: Gracillariidae: Epicephala) has colonized some of the world's most
      isolated archipelagoes, and we record, to our knowledge, for the first time the
      presence of Epicephala moths from 19 host Glochidion species on 17 islands in the
      Pacific Ocean. Our findings appear to offer a remarkable example of mutualism
      persistence in an insect-plant interaction characterized by reciprocal
      specialization and mutual dependence. These findings also appear to contradict
      the island biogeography paradigm that taxa with specialized biotic interactions
      are unlikely to colonize oceanic islands.

PMID- 21900313
TI  - The meaning of birth and death (in macroevolutionary birth-death models).
AB  - Birth-death models are central to much macroevolutionary theory. The fundamental
      parameters of these models concern durations. Different species concepts realize
      different species durations because they represent different ideas of what birth
      (speciation) and death (extinction) mean. Here, we use Cenozoic macroperforate
      planktonic foraminifera as a case study to ask: what are the dynamical
      consequences of changing the definition of birth and death? We show strong
      evidence for biotic constraints on diversification using evolutionary species,
      but less with morphospecies. Discussing reasons for this discrepancy, we
      emphasize that clarity of species concept leads to clarity of meaning when
      interpreting macroevolutionary birth-death models.

PMID- 21900314
TI  - Dolphin whistles: a functional misnomer revealed by heliox breathing.
AB  - Delphinids produce tonal whistles shaped by vocal learning for acoustic
      communication. Unlike terrestrial mammals, delphinid sound production is driven
      by pressurized air within a complex nasal system. It is unclear how fundamental
      whistle contours can be maintained across a large range of hydrostatic pressures
      and air sac volumes. Two opposing hypotheses propose that tonal sounds arise
      either from tissue vibrations or through actual whistle production from vortices
      stabilized by resonating nasal air volumes. Here, we use a trained bottlenose
      dolphin whistling in air and in heliox to test these hypotheses. The fundamental
      frequency contours of stereotyped whistles were unaffected by the higher sound
      speed in heliox. Therefore, the term whistle is a functional misnomer as dolphins
      actually do not whistle, but form the fundamental frequency contour of their
      tonal calls by pneumatically induced tissue vibrations analogous to the operation
      of vocal folds in terrestrial mammals and the syrinx in birds. This form of tonal
      sound production by nasal tissue vibrations has probably evolved in delphinids to
      enable impedance matching to the water, and to maintain tonal signature contours
      across changes in hydrostatic pressures, air density and relative nasal air
      volumes during dives.

PMID- 21900315
TI  - Father absence predicts age at sexual maturity and reproductive timing in British
      men.
AB  - Despite the widespread assumption that paternal investment is substantial in our
      species, previous studies have shown mixed results in relation to the impact of
      fathers on both offspring survival and reproductive outcomes. Using data from a
      large representative sample of British men, we tested whether father absence is
      associated with the timing of reproduction-related events among boys, while
      controlling for various cues denoting early childhood adversity. We further
      tested whether the loss of the father at different childhood stages matters, so
      as to assess whether early life is the most important period or if effects can be
      seen during later childhood. The results show that father absence before age
      seven is associated with early reproduction, while father absence between ages 11
      and 16 only is associated with delayed voice-breaking (a proxy for puberty), even
      after adjusting for other factors denoting childhood adversity. We conclude that
      fathers do exert an influence on male reproductive outcomes, independently of
      other childhood adversities and that these effects are sensitive to the timing of
      father absence.

PMID- 21900316
TI  - Context-dependent tool use in New Caledonian crows.
AB  - Humans and chimpanzees both exhibit context-dependent tool use. That is, both
      species choose to use tools when food is within reach, but the context is
      potentially hazardous. Here, we show that New Caledonian crows used tools more
      frequently when food was positioned next to a novel model snake than when food
      was positioned next to a novel teddy bear or a familiar food bowl. However, the
      crows showed no significant difference in their neophobic reactions towards the
      teddy bear and the model snake. Therefore, the crows used tools more in response
      to a risky object resembling a natural predator than to a less-threatening object
      that provoked a comparable level of neophobia. These results show that New
      Caledonian crows, like humans and chimpanzees, are capable of context-dependent
      tool use.

PMID- 21900317
TI  - Predicting ecosystem shifts requires new approaches that integrate the effects of
      climate change across entire systems.
AB  - Most studies that forecast the ecological consequences of climate change target a
      single species and a single life stage. Depending on climatic impacts on other
      life stages and on interacting species, however, the results from simple
      experiments may not translate into accurate predictions of future ecological
      change. Research needs to move beyond simple experimental studies and
      environmental envelope projections for single species towards identifying where
      ecosystem change is likely to occur and the drivers for this change. For this to
      happen, we advocate research directions that (i) identify the critical species
      within the target ecosystem, and the life stage(s) most susceptible to changing
      conditions and (ii) the key interactions between these species and components of
      their broader ecosystem. A combined approach using macroecology, experimentally
      derived data and modelling that incorporates energy budgets in life cycle models
      may identify critical abiotic conditions that disproportionately alter important
      ecological processes under forecasted climates.

PMID- 21900318
TI  - Gait recognition: highly unique dynamic plantar pressure patterns among 104
      individuals.
AB  - Everyone's walking style is unique, and it has been shown that both humans and
      computers are very good at recognizing known gait patterns. It is therefore
      unsurprising that dynamic foot pressure patterns, which indirectly reflect the
      accelerations of all body parts, are also unique, and that previous studies have
      achieved moderate-to-high classification rates (CRs) using foot pressure
      variables. However, these studies are limited by small sample sizes (n < 30),
      moderate CRs (CR ? 90%), or both. Here we show, using relatively simple image
      processing and feature extraction, that dynamic foot pressures can be used to
      identify n = 104 subjects with a CR of 99.6 per cent. Our key innovation was
      improved and automated spatial alignment which, by itself, improved CR to over 98
      per cent, a finding that pointedly emphasizes inter-subject pressure pattern
      uniqueness. We also found that automated dimensionality reduction invariably
      improved CRs. As dynamic pressure data are immediately usable, with little or no
      pre-processing required, and as they may be collected discreetly during
      uninterrupted gait using in-floor systems, foot pressure-based identification
      appears to have wide potential for both the security and health industries.

PMID- 21900320
TI  - Dynamics of alternative modes of RNA replication for positive-sense RNA viruses.
AB  - We propose and study nonlinear mathematical models describing the intracellular
      time dynamics of viral RNA accumulation for positive-sense single-stranded RNA
      viruses. Our models consider different replication modes ranging between two
      extremes represented by the geometric replication (GR) and the linear stamping
      machine replication (SMR). We first analyse a model that quantitatively
      reproduced experimental data for the accumulation dynamics of both polarities of
      turnip mosaic potyvirus RNAs. We identify a non-degenerate transcritical
      bifurcation governing the extinction of both strands depending on three key
      parameters: the mode of replication (alpha), the replication rate (r) and the
      degradation rate (delta) of viral strands. Our results indicate that the
      bifurcation associated with alpha generically takes place when the replication
      mode is closer to the SMR, thus suggesting that GR may provide viral strands with
      an increased robustness against degradation. This transcritical bifurcation,
      which is responsible for the switching from an active to an absorbing regime,
      suggests a smooth (i.e. second-order), absorbing-state phase transition. Finally,
      we also analyse a simplified model that only incorporates asymmetry in
      replication tied to differential replication modes.

PMID- 21900319
TI  - Biomaterial strategies for alleviation of myocardial infarction.
AB  - World Health Organization estimated that heart failure initiated by coronary
      artery disease and myocardial infarction (MI) leads to 29 per cent of deaths
      worldwide. Heart failure is one of the leading causes of death in industrialized
      countries and is expected to become a global epidemic within the twenty-first
      century. MI, the main cause of heart failure, leads to a loss of cardiac tissue
      impairment of left ventricular function. The damaged left ventricle undergoes
      progressive 'remodelling' and chamber dilation, with myocyte slippage and
      fibroblast proliferation. Repair of diseased myocardium with in vitro-engineered
      cardiac muscle patch/injectable biopolymers with cells may become a viable option
      for heart failure patients. These events reflect an apparent lack of effective
      intrinsic mechanism for myocardial repair and regeneration. Motivated by the
      desire to develop minimally invasive procedures, the last 10 years observed
      growing efforts to develop injectable biomaterials with and without cells to
      treat cardiac failure. Biomaterials evaluated include alginate, fibrin, collagen,
      chitosan, self-assembling peptides, biopolymers and a range of synthetic
      hydrogels. The ultimate goal in therapeutic cardiac tissue engineering is to
      generate biocompatible, non-immunogenic heart muscle with morphological and
      functional properties similar to natural myocardium to repair MI. This review
      summarizes the properties of biomaterial substrates having sufficient mechanical
      stability, which stimulates the native collagen fibril structure for
      differentiating pluripotent stem cells and mesenchymal stem cells into
      cardiomyocytes for cardiac tissue engineering.

PMID- 21900321
TI  - Mechanically induced structural changes during dynamic compression of engineered
      cartilaginous constructs can potentially explain increases in bulk mechanical
      properties.
AB  - Several studies on chondrocyte-seeded hydrogels in bioreactor culture report
      increased mechanical properties of mechanically loaded constructs compared with
      unloaded free swelling controls despite no significant differences in biochemical
      composition. One possible explanation is that changes in the collagen
      architecture of dynamically compressed constructs lead to improved mechanical
      properties. Collagen molecules are incorporated locally into the extracellular
      matrix with individual stress-free configurations and orientations. In this
      study, we computationally investigated possible influences of loading on the
      collagen architecture in chondrocyte-seeded hydrogels and their resulting
      mechanical properties. Both the collagen orientation and its stress-free
      configuration were hypothesized to depend on the local mechanical environment.
      Reorientation of the collagen network alone in response to dynamic compression
      leads to a prediction of constructs with lower compressive properties. In
      contrast, remodelling of the stress-free configuration of the collagen fibres was
      predicted to result in a more compacted tissue with higher swelling pressures and
      an altered pre-stressed state within the collagen network. Combining both
      mechanisms resulted in predictions of construct geometry and mechanical
      properties in agreement with experimental observations. This study provides
      support for the hypothesis that structural changes to the collagen network
      contribute to the enhanced mechanical properties of cartilaginous tissues
      engineered in bioreactors.

PMID- 21900322
TI  - The annual cycle of a trans-equatorial Eurasian-African passerine migrant:
      different spatio-temporal strategies for autumn and spring migration.
AB  - The small size of the billions of migrating songbirds commuting between temperate
      breeding sites and the tropics has long prevented the study of the largest part
      of their annual cycle outside the breeding grounds. Using light-level loggers
      (geolocators), we recorded the entire annual migratory cycle of the red-backed
      shrike Lanius collurio, a trans-equatorial Eurasian-African passerine migrant. We
      tested differences between autumn and spring migration for nine individuals.
      Duration of migration between breeding and winter sites was significantly longer
      in autumn (average 96 days) when compared with spring (63 days). This difference
      was explained by much longer staging periods during autumn (71 days) than spring
      (9 days). Between staging periods, the birds travelled faster during autumn (356
      km d(-1)) than during spring (233 km d(-1)). All birds made a protracted stop (53
      days) in Sahelian sub-Sahara on southbound migration. The birds performed a
      distinct loop migration (22 000 km) where spring distance, including a detour
      across the Arabian Peninsula, exceeded the autumn distance by 22 per cent.
      Geographical scatter between routes was particularly narrow in spring, with
      navigational convergence towards the crossing point from Africa to the Arabian
      Peninsula. Temporal variation between individuals was relatively constant, while
      different individuals tended to be consistently early or late at different
      departure/arrival occasions during the annual cycle. These results demonstrate
      the existence of fundamentally different spatio-temporal migration strategies
      used by the birds during autumn and spring migration, and that songbirds may rely
      on distinct staging areas for completion of their annual cycle, suggesting more
      sophisticated endogenous control mechanisms than merely clock-and-compass
      guidance among terrestrial solitary migrants. After a century with metal-ringing,
      year-round tracking of long-distance migratory songbirds promises further
      insights into bird migration.

PMID- 21900323
TI  - Separable temporal metrics for time perception and anticipatory actions.
AB  - Reliable estimates of time are essential for initiating interceptive actions at
      the right moment. However, our sense of time is surprisingly fallible. For
      instance, time perception can be distorted by prolonged exposure (adaptation) to
      movement. Here, we make use of this to determine if time perception and
      anticipatory actions rely on the same or on different temporal metrics.
      Consistent with previous reports, we find that the apparent duration of movement
      is mitigated by adaptation to more rapid motion, but is unchanged by adaptation
      to slower movement. By contrast, we find symmetrical effects of motion-adaptation
      on the timing of anticipatory interceptive actions, which are paralleled by
      changes in perceived speed for the adapted direction of motion. Our data thus
      reveal that anticipatory actions and perceived duration rely on different
      temporal metrics.

PMID- 21900324
TI  - A large population of king crabs in Palmer Deep on the west Antarctic Peninsula
      shelf and potential invasive impacts.
AB  - Lithodid crabs (and other skeleton-crushing predators) may have been excluded
      from cold Antarctic continental shelf waters for more than 14 Myr. The west
      Antarctic Peninsula shelf is warming rapidly and has been hypothesized to be soon
      invaded by lithodids. A remotely operated vehicle survey in Palmer Deep, a basin
      120 km onto the Antarctic shelf, revealed a large, reproductive population of
      lithodids, providing the first evidence that king crabs have crossed the
      Antarctic shelf. DNA sequencing and morphology indicate the lithodid is
      Neolithodes yaldwyni Ahyong & Dawson, previously reported only from Ross Sea
      waters. We estimate a N. yaldwyni population density of 10 600 km(-2) and a
      population size of 1.55 * 10(6) in Palmer Deep, a density similar to lithodid
      populations of commercial interest around Alaska and South Georgia. The lithodid
      occurred at depths of more than 850 m and temperatures of more than 1.4 degrees C
      in Palmer Deep, and was not found in extensive surveys of the colder shelf at
      depths of 430-725 m. Where N. yaldwyni occurred, crab traces were abundant,
      megafaunal diversity reduced and echinoderms absent, suggesting that the crabs
      have major ecological impacts. Antarctic Peninsula shelf waters are warming at
      approximately 0.01 degrees C yr(-1); if N. yaldwyni is currently limited by cold
      temperatures, it could spread up onto the shelf (400-600 m depths) within 1-2
      decades. The Palmer Deep N. yaldwyni population provides an important model for
      the potential invasive impacts of crushing predators on vulnerable Antarctic
      shelf ecosystems.

PMID- 21900325
TI  - Comparative multi-locus phylogeography confirms multiple vicariance events in co
      distributed rainforest frogs.
AB  - Though Pleistocene refugia are frequently cited as drivers of species
      diversification, comparisons of molecular divergence among sister species
      typically indicate a continuum of divergence times from the Late Miocene, rather
      than a clear pulse of speciation events at the Last Glacial Maximum. Community
      scale inference methods that explicitly test for multiple vicariance events, and
      account for differences in ancestral effective population size and gene flow, are
      well suited for detecting heterogeneity of species' responses to past climate
      fluctuations. We apply this approach to multi-locus sequence data from five co
      distributed frog species endemic to the Wet Tropics rainforests of northeast
      Australia. Our results demonstrate at least two episodes of vicariance owing to
      climate-driven forest contractions: one in the Early Pleistocene and the other
      considerably older. Understanding how repeated cycles of rainforest contraction
      and expansion differentially affected lineage divergence among co-distributed
      species provides a framework for identifying evolutionary processes that underlie
      population divergence and speciation.

PMID- 21900326
TI  - Mitochondrial DNA data indicate an introduction through Mainland Southeast Asia
      for Australian dingoes and Polynesian domestic dogs.
AB  - In the late stages of the global dispersal of dogs, dingoes appear in the
      Australian archaeological record 3500 years BP, and dogs were one of three
      domesticates brought with the colonization of Polynesia, but the introduction
      routes to this region remain unknown. This also relates to questions about human
      history, such as to what extent the Polynesian culture was introduced with the
      Austronesian expansion from Taiwan or adopted en route, and whether pre-Neolithic
      Australia was culturally influenced by the surrounding Neolithic world. We
      investigate these questions by mapping the distribution of the mtDNA founder
      haplotypes for dingoes (A29) and ancient Polynesian dogs (Arc1 and Arc2) in
      samples across Southern East Asia (n = 424) and Island Southeast Asia (n = 219).
      All three haplotypes were found in South China, Mainland Southeast Asia and
      Indonesia but absent in Taiwan and the Philippines, and the mtDNA diversity among
      dingoes indicates an introduction to Australia 4600-18 300 years BP. These
      results suggest that Australian dingoes and Polynesian dogs originate from dogs
      introduced to Indonesia via Mainland Southeast Asia before the Neolithic, and not
      from Taiwan together with the Austronesian expansion. This underscores the
      complex origins of Polynesian culture and the isolation from Neolithic influence
      of the pre-Neolithic Australian culture.

PMID- 21900327
TI  - Construction of energy landscapes can clarify the movement and distribution of
      foraging animals.
AB  - Variation in the physical characteristics of the environment should impact the
      movement energetics of animals. Although cognizance of this may help interpret
      movement ecology, determination of the landscape-dependent energy expenditure of
      wild animals is problematic. We used accelerometers in animal-attached tags to
      derive energy expenditure in 54 free-living imperial cormorants Phalacrocorax
      atriceps and construct an energy landscape of the area around a breeding colony.
      Examination of the space use of a further 74 birds over 4 years showed that
      foraging areas selected varied considerably in distance from the colony and water
      depth, but were characterized by minimal power requirements compared with other
      areas in the available landscape. This accords with classic optimal foraging
      concepts, which state that animals should maximize net energy gain by minimizing
      costs where possible and show how deriving energy landscapes can help understand
      how and why animals distribute themselves in space.

PMID- 21900328
TI  - The role of matrix proteins in the control of nacreous layer deposition during
      pearl formation.
AB  - To study the function of pearl oyster matrix proteins in nacreous layer
      biomineralization in vivo, we examined the deposition on pearl nuclei and the
      expression of matrix protein genes in the pearl sac during the early stage of
      pearl formation. We found that the process of pearl formation involves two
      consecutive stages: (i) irregular calcium carbonate (CaCO(3)) deposition on the
      bare nucleus and (ii) CaCO(3) deposition that becomes more and more regular until
      the mature nacreous layer has formed on the nucleus. The low-expression level of
      matrix proteins in the pearl sac during periods of irregular CaCO(3) deposition
      suggests that deposition may not be controlled by the organic matrix during this
      stage of the process. However, significant expression of matrix proteins in the
      pearl sac was detected by day 30-35 after implantation. On day 30, a thin layer
      of CaCO(3), which we believe was amorphous CaCO(3), covered large aragonites. By
      day 35, the nacreous layer had formed. The whole process is similar to that
      observed in shells, and the temporal expression of matrix protein genes indicated
      that their bioactivities were crucial for pearl development. Matrix proteins
      controlled the crystal phase, shape, size, nucleation and aggregation of CaCO(3)
      crystals.

PMID- 21900330
TI  - Multiple cenozoic invasions of Africa by penguins (Aves, Sphenisciformes).
AB  - Africa hosts a single breeding species of penguin today, yet the fossil record
      indicates that a diverse array of now-extinct taxa once inhabited southern
      African coastlines. Here, we show that the African penguin fauna had a complex
      history involving multiple dispersals and extinctions. Phylogenetic analyses and
      biogeographic reconstructions incorporating new fossil material indicate that,
      contrary to previous hypotheses, the four Early Pliocene African penguin species
      do not represent an endemic radiation or direct ancestors of the living
      Spheniscus demersus (blackfooted penguin). A minimum of three dispersals to
      Africa, probably assisted by the eastward-flowing Antarctic Circumpolar and South
      Atlantic currents, occurred during the Late Cenozoic. As regional sea-level fall
      eliminated islands and reduced offshore breeding areas during the Pliocene, all
      but one penguin lineage ended in extinction, resulting in today's depleted fauna.

PMID- 21900329
TI  - Is titin a 'winding filament'? A new twist on muscle contraction.
AB  - Recent studies have demonstrated a role for the elastic protein titin in active
      muscle, but the mechanisms by which titin plays this role remain to be
      elucidated. In active muscle, Ca(2+)-binding has been shown to increase titin
      stiffness, but the observed increase is too small to explain the increased
      stiffness of parallel elastic elements upon muscle activation. We propose a
      'winding filament' mechanism for titin's role in active muscle. First, we
      hypothesize that Ca(2+)-dependent binding of titin's N2A region to thin filaments
      increases titin stiffness by preventing low-force straightening of proximal
      immunoglobulin domains that occurs during passive stretch. This mechanism
      explains the difference in length dependence of force between skeletal myofibrils
      and cardiac myocytes. Second, we hypothesize that cross-bridges serve not only as
      motors that pull thin filaments towards the M-line, but also as rotors that wind
      titin on the thin filaments, storing elastic potential energy in PEVK during
      force development and active stretch. Energy stored during force development can
      be recovered during active shortening. The winding filament hypothesis accounts
      for force enhancement during stretch and force depression during shortening, and
      provides testable predictions that will encourage new directions for research on
      mechanisms of muscle contraction.

PMID- 21900331
TI  - Technique of recanalization of long-segment flush superior mesenteric artery
      occlusions.
AB  - PURPOSE: To describe technical tips for recanalization of long-segment flush
      superior mesenteric artery (SMA) occlusions. TECHNIQUE: Ultrasound-guided left
      brachial artery access was gained in 2 patients with a 7F 90-cm sheath being
      advanced to the supraceliac aorta. The SMA stump was visualized using a selective
      inferior mesenteric artery (IMA) catheterization via femoral approach. A
      combination of a 7F 100-cm Multipurpose (MPA) guide and a 5F 125-cm MPA catheter
      was utilized to provide support for selective catheterization. Subsequently, a
      0.018-inch wire and catheter were advanced crossing the area of occlusion.
      Predilatation was performed, followed by placement of covered stent. Both
      patients had uncomplicated course and resolution of symptoms. CONCLUSION: Flush
      SMA occlusions are challenging lesions but may be treated by antegrade
      percutaneous recanalization with good results. Technical aspects that facilitate
      recanalization include brachial approach, use of a stiff system (sheath, guide,
      and catheter) and concomitant injection to facilitate visualization of the SMA
      stump.

PMID- 21900332
TI  - Transradial access for renal artery intervention is feasible and safe.
AB  - BACKGROUND: Transradial access for coronary intervention is associated with
      reduced access complications compared with transfemoral. Transradial access for
      renal artery intervention has been less well studied. Safety compared with
      transfemoral access is undetermined. METHODS AND RESULTS: We evaluated the
      feasibility of transradial renal intervention (n = 11 patients) and compared
      safety parameters with a matched group of transfemoral controls (n = 44). All
      transradial interventions were successful with no complications. Femoral
      crossover was required in one due to insufficient guide length. Compared with
      transfemoral, there were fewer access complications in the transradial group (0
      of 11 vs 3 of 44, P = .06) but no differences in fluoroscopy time or contrast
      volumes (25.3 +/- 14.4 vs 29.0 +/- 25.1 minutes, P = .47; 83.0 +/- 43.7 vs 82.6
      +/- 35.2 cc, P = .97). At follow-up (median 6 months), radial patency was 100%.
      Creatinine and systolic blood pressure had decreased (mean 1.4 +/- 0.5 to 1.2 +/-
      0.5, P = .06; 160 +/- 25 to 135 +/- 17, P = .009). CONCLUSIONS: Elective
      transradial renal intervention is feasible and safe. Radial-renal distance is a
      limitation with available guides.

PMID- 21900333
TI  - Uterine transplantation research: laboratory protocols for clinical application.
AB  - The aim of this review is to summarize the state-of the-art methods that are used
      in clinical organ transplantation today, as well as the major findings of recent
      experimental uterus transplantation (UTx) research regarding organ
      donation/retrieval, ischemic preservation, surgical techniques for anastomosis,
      immunosuppression and pregnancy. Absolute uterine factor infertility lacks
      treatment despite the major developments in infertility treatment and assisted
      reproduction. Concerning uterine factor infertile patients, genetic motherhood is
      only possible through gestational surrogacy. The latter can pose medical, ethical
      and legal concerns such as lack of control of life habits during surrogate
      pregnancy, economic motives for women to become surrogate mothers,
      medical/psychological pregnancy-related risks of the surrogate mother and
      uncertainties regarding the mother definition. Thus, surrogacy is non-approved in
      large parts of the world. Recent advances in the field of solid organ
      transplantation and experimental UTx provide a favourable and safe background in
      a scenario in which a human clinical UTx trial can take place. Protocols based on
      animal research over the last decade are described with a view to providing a
      scientifically guided approach to human UTx as an experimental procedure in the
      future.

PMID- 21900334
TI  - Evaluation of a completely automated tissue-sectioning machine for paraffin
      blocks.
AB  - Tissue-sectioning automation can be a resourceful tool in processing anatomical
      pathology specimens. The advantages of an automated system compared with
      traditional manual sectioning are the invariable thickness, uniform orientation
      and fewer tissue-sectioning artefacts. This short report presents the design of
      an automated tissue-sectioning device and compares the sectioned specimens with
      normal manual tissue sectioning performed by an experienced histology technician.
      The automated system was easy to use, safe and the sectioned material showed
      acceptable quality with well-preserved morphology and tissue antigenicity. It is
      expected that the turnaround time will be improved in the near future.

PMID- 21900335
TI  - Communication and culture: predictors of treatment adherence among Mexican
      immigrant patients.
AB  - This study examined communication and culture in clinicians' interactions with
      Mexican immigrants in Texas. Specifically, we explore the unique interplay among
      levels of acculturation, beliefs about culturally-based medical practices,
      perceptions of medical encounters, and the likelihood of adherence to medical
      therapy recommendations from US providers. Results suggest that: (a)
      acculturation predicts perceptions of out-group membership in the patient
      provider interaction; (b) beliefs about complementary and alternative medicine
      are negatively related to medical adherence; (c) quality of care mediates the
      relationship between physician accommodation and medical adherence; and (d) there
      exists a complex relationship between out-group perceptions and adherence.

PMID- 21900336
TI  - Editorial: guidance for submitting and reviewing case reports and series in the
      Journal of Pediatric Psychology.

PMID- 21900338
TI  - Getting inside the black box of health promotion programmes using intervention
      Mapping.

PMID- 21900339
TI  - When is patient self-management of chronic disease futile?

PMID- 21900340
TI  - Strategies for successful rapid trials of influenza vaccine.
AB  - BACKGROUND: In contrast to the gradual pace of conventional vaccine trials,
      evaluation of influenza vaccines often must be accelerated for use in a pandemic
      or for annual re-licensure. Descriptions of how best to design studies for rapid
      completion are few. PURPOSE: In August, 2010, we conducted a rapid trial with a
      seasonal influenza vaccine for 2010-2011 given to persons vaccinated with an
      adjuvanted H1N1 vaccine in 2009, to determine whether re-exposure to the
      H1N1(2009) component of the seasonal vaccine would cause increased reactions. We
      describe the strategies that we believe were responsible for success in meeting
      the desired timeline. METHODS: The key means for expediting the study were: use
      of a few experienced, well-staffed centers; efficient completion of
      administrative approvals; advance recruitment of volunteers; synchronized start
      among centers with rapid completion (<=1 week) of first visits; rapid data
      assembly via the Internet; and a well-prepared data analysis plan. We chose to
      use a randomized, blinded, cross-over design to allow estimation of vaccine
      attributable adverse event rates, with sufficient power (320 participants) to
      detect events occurring at true rates >=1% with >=90% probability. RESULTS:
      Planned enrollment numbers, center synchronization, and timelines, including
      review by a safety board prior to the cross-over step (second doses), were
      achieved. A detailed safety report was delivered to federal health officials just
      32 days after study initiation and was used to fine-tune public messaging prior
      to the mass vaccination programs across Canada. LIMITATIONS: This aggressive
      timeline could not have been met without opportunities for careful planning and
      the prior existence of a network of experienced, collaborating trial centers.
      CONCLUSIONS: The means used to accelerate this study timeline were successful and
      could be used in other urgent situations but the mechanics of collaborative
      trials must be well rehearsed as a precondition.

PMID- 21900341
TI  - Design and implementation of an audit trail in compliance with US regulations.
AB  - BACKGROUND: Audit trails have been used widely to ensure quality of study data
      and have been implemented in computerized clinical trials data systems.
      Increasingly, there is a need to audit access to study participant identifiable
      information to provide assurance that study participant privacy is protected and
      confidentiality is maintained. In the United States, several federal regulations
      specify how the audit trail function should be implemented. PURPOSE: To describe
      the development and implementation of a comprehensive audit trail system that
      meets the regulatory requirements of assuring data quality and integrity and
      protecting participant privacy and that is also easy to implement and maintain.
      METHODS: The audit trail system was designed and developed after we examined
      regulatory requirements, data access methods, prevailing application
      architecture, and good security practices. RESULTS: Our comprehensive audit trail
      system was developed and implemented at the database level using a commercially
      available database management software product. It captures both data access and
      data changes with the correct user identifier. Documentation of access is
      initiated automatically in response to either data retrieval or data change at
      the database level. LIMITATIONS: Currently, our system has been implemented only
      on one commercial database management system. Although our audit trail algorithm
      does not allow for logging aggregate operations, aggregation does not reveal
      sensitive private participant information. Careful consideration must be given to
      data items selected for monitoring because selection of all data items using our
      system can dramatically increase the requirements for computer disk space.
      Evaluating the criticality and sensitivity of individual data items selected can
      control the storage requirements for clinical trial audit trail records.
      CONCLUSIONS: Our audit trail system is capable of logging data access and data
      change operations to satisfy regulatory requirements. Our approach is applicable
      to virtually any data that can be stored in a relational database.

PMID- 21900342
TI  - The utility of collaborative biobanks for cardiovascular research.
AB  - Differences between animal and human atherosclerosis have led to the requirement
      for clinical data, imaging information and biological material from large numbers
      of patients and healthy persons. Where such "biobanks" exist, they have been
      fruitful sources for genomewide association, diagnostic accuracy, ethnicity, and
      risk stratification cohort studies. In addition once established, they attract
      funding for future projects. Biobanks require a network of medical contributors,
      secure storage facilities, bioinformatics expertise, database managers, and
      ethical working practices to function optimally. There is the opportunity for
      collaboration between individual biobanks to further amplify the advantages
      afforded.

PMID- 21900343
TI  - Rapamycin affects tissue plasminogen activator and plasminogen activator
      inhibitor I expression: a potential prothrombotic mechanism of drug-eluting
      stents.
AB  - Although drug-eluting stents (DESs) can decrease the risk of restenosis, this
      benefit is tempered by a possible increased risk of in-stent thrombosis. We
      assessed the effects of rapamycin on human umbilical vein endothelial cells
      (HUVECs) to identify the alterations in gene expression associated with
      thrombosis. Expression of tissue plasminogen activator (t-PA) and plasminogen
      activator inhibitor 1 (PAI-1) was assessed in HUVECs treated with rapamycin
      (final concentrations: 1, 10, 100, and 1000 ng/mL) for 24 and 48 hours.
      Incubation of HUVECs with rapamycin strongly reduced the expression of t-PA in a
      concentration-dependant manner (P < .05 to < .01). However, the expression of PAI
      1 was induced by rapamycin (P < .05 to < .01). The increase in PAI-1 induction
      was up to 3.3-fold. In conclusion, rapamycin inhibited t-PA and induced PAI-1
      expression in HUVECs. This effect may contribute to in-stent thrombosis
      associated with DESs.

PMID- 21900344
TI  - ACOs, PCMHs, and health care reform: nursing's next frontier?
AB  - National health reform includes an emphasis on integrated service delivery models
      including Accountable Care Organizations and Patient-Centered Medical Homes.
      These value-based models of care delivery may offer opportunities for nursing to
      advance its patient care and profession. This paper presents four pillars of
      health care delivery reform-team-based care; cross-team communication,
      coordination and collaboration; infrastructure and technology; and aligned
      payment incentives -intended to improve quality of care while reducing cost
      increases. Opportunities and challenges for nursing are discussed in this
      context.

PMID- 21900345
TI  - Cognitive assessment of older people.

PMID- 21900346
TI  - The politics of NHS reconfiguration.

PMID- 21900347
TI  - Trans fats: chasing a global ban.

PMID- 21900348
TI  - Adult and child asylum seekers should be treated with humanity.

PMID- 21900349
TI  - Islamic medical association.

PMID- 21900350
TI  - Different bodies, different futures.

PMID- 21900351
TI  - New NICE guidelines for hypertension.

PMID- 21900352
TI  - Sierra Leone's maternal health reforms fail to deliver free treatment, says
      Amnesty International.

PMID- 21900353
TI  - No trivial pursuit.

PMID- 21900354
TI  - Bahraini doctors start hunger strike over arrests and trials in military court.

PMID- 21900355
TI  - Evidence is poor that financial incentives in primary care improve patients'
      wellbeing, Cochrane review finds.

PMID- 21900356
TI  - Early onset of natalizumab-related progressive multifocal leukoencephalopathy.

PMID- 21900358
TI  - Waste management and producer responsibility: a score behind: a new ahead.

PMID- 21900357
TI  - Modeling familial Alzheimer's disease with induced pluripotent stem cells.
AB  - Alzheimer's disease (AD) is the most common form of age-related dementia,
      characterized by progressive memory loss and cognitive disturbance. Mutations of
      presenilin 1 (PS1) and presenilin 2 (PS2) are causative factors for autosomal
      dominant early-onset familial AD (FAD). Induced pluripotent stem cell (iPSC)
      technology can be used to model human disorders and provide novel opportunities
      to study cellular mechanisms and establish therapeutic strategies against various
      diseases, including neurodegenerative diseases. Here we generate iPSCs from
      fibroblasts of FAD patients with mutations in PS1 (A246E) and PS2 (N141I), and
      characterize the differentiation of these cells into neurons. We find that FAD
      iPSC-derived differentiated neurons have increased amyloid beta42 secretion,
      recapitulating the molecular pathogenesis of mutant presenilins. Furthermore,
      secretion of amyloid beta42 from these neurons sharply responds to gamma
      secretase inhibitors and modulators, indicating the potential for identification
      and validation of candidate drugs. Our findings demonstrate that the FAD-iPSC
      derived neuron is a valid model of AD and provides an innovative strategy for the
      study of age-related neurodegenerative diseases.

PMID- 21900360
TI  - Does household enrolment reduce adverse selection in a voluntary health insurance
      system? Evidence from the Ghanaian National Health Insurance System.
AB  - In August 2003, the Ghanaian Government made history by implementing the first
      National Health Insurance System (NHIS) in sub-Saharan Africa. Within 2 years,
      over one-third of the country had voluntarily enrolled in the NHIS. To discourage
      households from selectively enrolling their sickest (high-risk) members, the NHIS
      in the Nkoranza district offered premium waivers for all children under 18 in
      exchange for full household enrolment. This study aimed to test whether, despite
      this incentive, there is evidence suggestive of adverse selection. To accomplish
      this, we examined how the observed pay-off from insurance (odds and intensity of
      medical consumption) responds to changes in the family enrolment cost. If adverse
      selection were present, we would expect the odds and intensity of medical
      consumption to increase with family enrolment cost. A number of econometric tests
      were conducted using the claims database of the NHIS in Nkoranza. Households with
      full enrolment were analysed, for a total of 58 516 individuals from 12 515
      households. Our results show that household enrolment cost is not correlated with
      (1) odds or intensity of inpatient use or (2) odds of adult outpatient use, and
      is weakly correlated with the intensity of outpatient use. We also find that
      household enrolment costs are positively correlated with the number of children
      in the household and the odds and intensity of outpatient use by children. Thus,
      we conclude that the child-premium waiver is an important incentive for household
      enrolment. This evidence suggests that adverse selection has effectively been
      contained, but not eliminated. We argue that since one of the main objectives of
      the NHIS was to increase use of necessary care, especially by children, our
      findings indicate a largely favourable policy outcome, but one that may carry
      negative financial consequences. Policy makers must balance the fiscal need to
      contain costs with the societal objective to cover vulnerable populations.

PMID- 21900361
TI  - Retention of female volunteer community health workers in Dhaka urban slums: a
      case-control study.
AB  - INTRODUCTION: Volunteer community health workers (CHWs) are one approach to
      addressing the health workforce shortage in developing countries. BRAC, a large
      NGO in Bangladesh, is a pioneer in using female volunteer CHWs as core workers in
      its successful health programmes. After 25 years of implementing the CHW model in
      rural areas, BRAC is now using CHWs in urban slums of Dhaka through Manoshi, a
      community-based maternal and child health project. However, high dropout rates
      among CHWs in the slums suggested a need to better understand factors associated
      with their retention, and consequently recommend strategies for increasing their
      retention. METHODS: This mixed-method study included a case-control design to
      assess factors relating to the retention of volunteer CHWs, and focus group
      discussions (FGDs) to explore solutions to problems. In total, 542 current and
      146 dropout CHWs participated in the survey. Six FGDs were held with groups of
      current and groups of dropout CHWs. RESULTS: Financial incentives were the main
      factor linked to CHW retention. CHWs who joined with the expectation of income
      were almost twice as likely to remain as CHWs. This finding was reinforced by the
      inverse association between wealth quintile of the CHWs and retention; the
      poorest CHWs were significantly more likely to stay in the programme than the
      richest. However, social prestige, community approval and household
      responsibilities were important non-financial factors associated with CHW
      retention. Restructuring and expansion of existing financial incentives to better
      compensate CHWs were recommended by CHWs to improve their retention. CONCLUSIONS:
      Factors found to be important in this study are similar to those from earlier
      studies in rural areas. While the data indicate that financial incentives are the
      most commonly discussed factor regarding CHW retention in urban slums, the
      results also suggest other avenues that could be strengthened to improve their
      retention.

PMID- 21900362
TI  - A new phage-display tumor-homing peptide fused to antiangiogenic peptide
      generates a novel bioactive molecule with antimelanoma activity.
AB  - Phage-display peptide libraries have been widely used to identify specific
      peptides targeting in vivo tumor cells and the tumor vasculature and playing an
      important role in the discovery of antitumor bioactive peptides. In the present
      work, we identified a new melanoma-homing peptide, (-CVNHPAFAC-), using a C7C
      phage-display library directed to the developing tumor in syngeneic mice. Phage
      were able to preferentially target melanoma in vivo, with an affinity about 50
      fold greater than that with normal tissue, and the respective synthesized peptide
      displaced the corresponding phage from the tumor. A preferential binding to
      endothelial cells rather than to melanoma cells was seen in cell ELISA,
      suggesting that the peptide is directed to the melanoma vasculature. Furthermore,
      the peptide was able to bind to human sonic hedgehog, a protein involved in the
      development of many types of human cancers. Using a new peptide approach therapy,
      we coupled the cyclic peptide to another peptide, HTMYYHHYQHHL-NH(2), a known
      antagonist of VEGFR-2 receptor, using the GYG linker. The full peptide
      CVNHPAFACGYGHTMYYHHYQHHL-NH(2) was effective in delaying tumor growth (P < 0.05)
      and increasing animal survival when injected systemically, whereas a scramble
      homing peptide containing the same antagonist did not have any effect. This is
      the first report on the synthesis of a tumor-homing peptide coupled to
      antiangiogenic peptide as a new anticancer therapeutics.

PMID- 21900363
TI  - Physical activity is inversely associated with microalbuminuria in hypertensive
      patients at high cardiovascular risk: data from I-SEARCH.
AB  - AIMS: Microalbuminuria (MAU) is a marker for endothelial dysfunction and a
      predictor of increased cardiovascular risk. Physical activity improves
      endothelial function. This analysis aims to explore the impact of regular
      physical exercise on the prevalence and the degree of MAU in hypertensive
      individuals at high cardiovascular risk. METHODS AND RESULTS: The International
      Survey Evaluating microAlbuminuria Routinely by Cardiologists in patients with
      Hypertension (I-SEARCH) studied the prevalence of MAU in 20,786 hypertensive
      patients at high cardiovascular risk. Herein, we investigated the relationship
      between self-reported physical activity and MAU in relation to the number of
      cardiovascular risk factors, medication and co-morbidities. A total of 7123
      patients (34.3%) performed regular physical exercise (moderate or strenuous, at
      least 4 hours per week). The prevalence of MAU was significantly lower in active
      than in inactive patients (54% vs 61%; P < 0.0001). This association was observed
      in all classes of blood pressure and heart rate and was similar in patients with
      and without diabetes mellitus. Urinary albumin excretion (UAE) was lower in
      active than in inactive patients (UAE 80 mg/l: 11.6% vs 13.5%, P < 0.0001; UAE
      150 mg/l: 7.5% vs 10%; P < 0.0001). In a multivariate analysis adjusted for age,
      gender, blood pressure, heart rate, renal function, medication and comorbidities,
      regular physical activity was associated with a 25% lower risk for MAU (odds
      ratio (OR) 0.75; 95% confidence interval (CI), 0.67-0.84; P < 0.0001). Risk
      reduction for MAU was more pronounced in strenuously active (OR 0.66; 95%CI, 0.47
      0.95; P < 0.05) than in moderately active patients (OR 0.76; 95%CI, 0.68-0.85; P
      < 0.0001). CONCLUSION: In hypertensive patients at high cardiovascular risk,
      physical activity is an independent predictor for a decreased risk of
      microalbuminuria.

PMID- 21900365
TI  - Inflammatory and thrombotic changes in early bereavement: a prospective
      evaluation.
AB  - AIMS: Although there is an increased cardiovascular risk in the immediate weeks
      following bereavement, the mechanism is not well understood. The aim of this
      study was to determine whether inflammatory and thrombotic changes were present
      in acute bereavement. METHODS AND RESULTS: Eighty bereaved spouses or parents
      were prospectively studied within 2 weeks of bereavement (acute) and at 6 months,
      and compared to 80 non-bereaved participants. Haemostatic measures were obtained
      between 8 a.m. and 11 a.m. and processed within 1 h. Compared to non-bereaved
      participants, those acutely bereaved had a higher neutrophil count (4.34 +/- 0.19
      vs 3.79 +/- 0.15, p = <0.001), von Willebrand factor antigen (132.33 +/- 3.6 vs
      119.95 +/- 3.29, p = 0.02), Factor VIII (1.43 +/- 0.06 vs 1.25 +/- 0.04, p =
      0.02) and platelet/granulocyte aggregates (median 383.0 vs 343.5, p = 0.02).
      Levels of neutrophils, monocytes, eosinophils, platelet count, platelet/monocyte
      granulocytes and von Willebrand factor were lower in bereaved at 6 months
      compared to acutely (all p < 0.05). CONCLUSION: Acute bereavement is associated
      with inflammatory and prothrombotic changes that may contribute to the increased
      cardiovascular risk with bereavement and provide clues for future preventative
      strategies.

PMID- 21900366
TI  - Prognostic value of high-sensitivity C-reactive protein in a population of post
      acute coronary syndrome patients receiving optimal medical treatment.
AB  - BACKGROUND: High-sensitivity C-reactive protein (hsCRP) has been reported to have
      a prognostic value immediately after acute coronary syndrome (ACS) and to be
      associated with the onset of cardiovascular (CV) events in patients with stable
      and unstable angina pectoris. AIM: To evaluate whether or not hsCRP levels can be
      used to predict future CV events in a prospective study of post-ACS patients
      receiving an optimized medical treatment (OMT) secondary-prevention regimen.
      METHODS: OMT along with therapeutic and dietary education programmes were started
      during the acute phase, then monitored and adjusted as needed at 3 months post
      ACS. hsCRP was measured at 3 months after the ACS, and a global evaluation of
      atherosclerosis burden and risk factors were also evaluated at this time point.
      The study population was divided into tertiles based on their hsCRP value and
      followed for CV events. RESULTS: A total of 1202 consecutive patients with hsCRP
      <15 mg/l were included in the study, 795 of which were followed for an average of
      22 months. LDL-cholesterol, HbA(1c), waist circumference, systolic blood
      pressure, metabolic syndrome, tobacco consumption, and atherosclerosis burden
      were higher in patients in the second and third tertile of hsCRP (p < 0.001) than
      those in the first tertile, at 3 months. hsCRP level was not found to be
      associated with recurrence of total CV events (HR 1.29, CI 0.83-2.00) in
      univariate analysis. We further examined the effect of adding hsCRP levels to the
      Framingham risk evaluation score, and found no significant improvement the C
      statistics of the Framingham risk evaluation score. CONCLUSION: hsCRP is
      associated with CV risk factors, but is not an independent predictor of future
      events in post-ACS patients receiving an OMT secondary-prevention regimen.

PMID- 21900367
TI  - Effect of shift work on endothelial function in young cardiology trainees.
AB  - BACKGROUND: Long-term shift work (SW) is associated with an increase in
      cardiovascular disease (CVD). Previous studies have shown that prolonged SW is
      associated with endothelial dysfunction, suggesting that this abnormality may
      contribute to the SW-related increase in cardiovascular risk. The immediate
      effect of SW on endothelial function in healthy subjects, however, is unknown.
      DESIGN: We studied endothelial function and endothelium-independent function in
      20 healthy specialty trainees in cardiology at our Institute, without any
      cardiovascular risk factor (27.3 +/- 1.9 years, nine males), at two different
      times: (1) after a working night (WN), and (2) after a restful night (RN). The
      two test sessions were performed in a random sequence. METHODS: Endothelial
      function was assessed by measuring brachial artery dilation during post-ischaemic
      forearm hyperaemia (flow-mediated dilation, FMD). Endothelium-independent
      function in response to 25 ug of sublingual glyceryl trinitrate (nitrate-mediated
      dilation, NMD) was also assessed. RESULTS: FMD was 8.02 +/- 1.4% and 8.56 +/-
      1.7% after WN and RN, respectively (p = 0.025), whereas NMD was 10.5 +/- 2.1% and
      10.4 +/- 2.0% after WN and RN, respectively (p = 0.48). The difference in FMD
      between WN and RN was not influenced by the numbers of hours slept during WN (<4
      vs >4 hours) and by the duration of involvement of specialty trainees in
      nocturnal work (<12 vs >12 months). CONCLUSIONS: Our study shows that in healthy
      medical residents, without any cardiovascular risk factor, FMD is slightly
      impaired after WN compared to RN. Disruption of physiological circadian neuro
      humoral rhythm is likely to be responsible for this adverse vascular effect.

PMID- 21900368
TI  - Trends in mortality in patients with systemic sclerosis over 40 years: a
      systematic review and meta-analysis of cohort studies.
AB  - OBJECTIVE: SSc is known as the most severe connective tissue disorder, and to be
      associated with a high mortality risk. Some improvements in therapy for SSc have
      been achieved in recent years and some preliminary data have suggested an
      improvement in patient survival. Thus, we set out to determine whether mortality
      rate in SSc patients has decreased over the past 40 years through a meta-analysis
      of cohort studies. METHODS: We performed a systematic review and a meta-analysis
      of literature in MEDLINE and Embase databases from January 1960 to June 2010. All
      cohort studies reporting on SSc mortality were analysed. We then calculated
      pooled standardized mortality ratios (SMRs) of SSc mortality and calculated their
      changes over time using meta-regression analysis. RESULTS: Nine studies were
      included, corresponding to a total of 2691 SSc patients. The pooled SMR was 3.53
      [95% CI 3.03, 4.11, P < 0.0001; I(2 )= 93%, P(het) = 0.001]. Mid-cohort year
      ranged from 1977 to 1995 (before 1980: two studies; 1980-90: five studies; and
      after 1990: two studies): adjusted meta-regression analysis did not show
      significant change in SMR over time (P = 0.523). Among 732 deaths, heart
      involvement was the most frequent cause of deaths (29%) followed by lung
      involvement. CONCLUSION: Our results confirm that SSc is a devastating condition
      as reflected by a pooled SMR of 3.5. Additionally, SMR has not significantly
      changed over the past 40 years. Further studies are needed to assess the effect
      of the most recent available therapies on mortality in SSc.

PMID- 21900369
TI  - IL-6 inhibition and infection: treating patients with tocilizumab.

PMID- 21900370
TI  - Inhibition of target detection in apparent motion trajectory.
AB  - Letter discrimination performance is degraded when a letter is presented within
      an apparent motion (AM) trajectory of a spot. This finding suggests that the
      internal representation of AM stimuli can perceptually interact with other
      stimuli. In this study, we demonstrated that AM interference could also occur for
      pattern detection. We found that target (Gabor patch) detection performance was
      degraded within an AM trajectory. Further, this AM interference weakened when the
      differences in orientation between the AM stimuli and target became greater. We
      also revealed that AM interference occurred for the target with spatiotemporally
      intermediate orientations of the inducers that changed their orientation during
      AM. In contrast, the differences in phase among the stimuli did not affect the
      occurrence of AM interference. These findings suggest that AM stimuli and their
      internal representations affect lower visual processes involved in detecting a
      pattern in the AM trajectory and that the internal object representation of an AM
      stimulus selectively reflects and maintains the stimulus attribute.

PMID- 21900371
TI  - The horizontal tuning of face perception relies on the processing of intermediate
      and high spatial frequencies.
AB  - It was recently shown that expert face perception relies on the extraction of
      horizontally oriented visual cues. Picture-plane inversion was found to eliminate
      horizontal, suggesting that this tuning contributes to the specificity of face
      processing. The present experiments sought to determine the spatial frequency
      (SF) scales supporting the horizontal tuning of face perception. Participants
      were instructed to match upright and inverted faces that were filtered both in
      the frequency and orientation domains. Faces in a pair contained horizontal or
      vertical ranges of information in low, middle, or high SF (LSF, MSF, or HSF). Our
      findings confirm that upright (but not inverted) face perception is tuned to
      horizontal orientation. Horizontal tuning was the most robust in the MSF range,
      next in the HSF range, and absent in the LSF range. Moreover, face inversion
      selectively disrupted the ability to process horizontal information in MSF and
      HSF ranges. This finding was replicated even when task difficulty was equated
      across orientation and SF at upright orientation. Our findings suggest that
      upright face perception is tuned to horizontally oriented face information
      carried by intermediate and high SF bands. They further indicate that inversion
      alters the sampling of face information both in the orientation and SF domains.

PMID- 21900372
TI  - Spatial updating across saccades during manual interception.
AB  - We studied the effect of intervening saccades on the manual interception of a
      moving target. Previous studies suggest that stationary reach goals are coded and
      updated across saccades in gaze-centered coordinates, but whether this
      generalizes to interception is unknown. Subjects (n = 9) reached to manually
      intercept a moving target after it was rendered invisible. Subjects either
      fixated throughout the trial or made a saccade before reaching (both fixation
      points were in the range of -10 degrees  to 10 degrees ). Consistent with
      previous findings and our control experiment with stationary targets, the
      interception errors depended on the direction of the remembered moving goal
      relative to the new eye position, as if the target is coded and updated across
      the saccade in gaze-centered coordinates. However, our results were also more
      variable in that the interception errors for more than half of our subjects also
      depended on the goal direction relative to the initial gaze direction. This
      suggests that the feedforward transformations for interception differ from those
      for stationary targets. Our analyses show that the interception errors reflect a
      combination of biases in the (gaze-centered) representation of target motion and
      in the transformation of goal information into body-centered coordinates for
      action.

PMID- 21900373
TI  - Delays in using chromatic and luminance information to correct rapid reaches.
AB  - People can use feedback to make online corrections to movements but only if there
      is sufficient time to integrate the new information and make the correction. A
      key variable in this process is therefore the speed at which the new information
      about the target location is coded. Conduction velocities for chromatic signals
      are lower than for achromatic signals so it may take longer to correct reaches to
      chromatic stimuli. In addition to this delay, the sensorimotor system may prefer
      achromatic information over the chromatic information as delayed information may
      be less valuable when movements are made under time pressure. A down-weighting of
      chromatic information may result in additional latencies for chromatically
      directed reaches. In our study, participants made online corrections to reaches
      to achromatic, (L-M)-cone, and S-cone stimuli. Our chromatic stimuli were
      carefully adjusted to minimize stimulation of achromatic pathways, and we equated
      stimuli both in terms of detection thresholds and also by their estimated neural
      responses. Similar stimuli were used throughout the subjective adjustments and
      final reaching experiment. Using this paradigm, we found that responses to
      achromatic stimuli were only slightly faster than responses to (L-M)-cone and S
      cone stimuli. We conclude that the sensorimotor system treats chromatic and
      achromatic information similarly and that the delayed chromatic responses
      primarily reflect early conduction delays.

PMID- 21900374
TI  - The health-related quality of life of children with hereditary retinal disorders
      and the psychosocial impact on their families.
AB  - PURPOSE: Childhood-onset hereditary retinal disorders comprise a group of
      visually disabling conditions with variable onset and progression of visual
      impairment. Their impact on the health-related quality of life (HRQoL) of
      affected individuals, as well as the broader impact on their families has not
      been investigated previously. METHODS: In a cross-sectional study, a generic age
      appropriate instrument, the PedsQL, was used to assess self-reported HRQoL in a
      subsample of a representative group of children with hereditary retinal disorders
      and their siblings as well as parental (proxy) assessment of HRQoL of their
      affected children. In addition, parents reported the broader impact and effect on
      functioning of the family using the PedsQL Family Impact Module. RESULTS:
      Affected children (n = 44) reported worse HRQoL than their unaffected siblings (n
      = 34) and notably, also worse scores than those reported by children with various
      serious chronic systemic disorders. On average, parents assessed their child's
      HRQoL to be worse than that self-reported by the child. There was an overall
      adverse impact on the family and its functioning, although siblings did not
      report impaired HRQoL themselves. CONCLUSIONS: This study demonstrates the
      significant impact, on both affected children and their families, of living with
      an untreatable, often progressive, and sometimes blinding ophthalmic disorder. It
      highlights the importance of support for affected individuals and their families,
      which may be targeted through use of generic or vision-related quality-of-life
      instruments for children as the latter become more widely available. Assessment
      of HRQoL would also be an important outcome measure in clinical trials of novel
      therapies for hereditary retinal disorders.

PMID- 21900375
TI  - Immunocytochemical and ultrastructural evidence of glial cells and hyalocytes in
      internal limiting membrane specimens of idiopathic macular holes.
AB  - PURPOSE: To provide new information on epiretinal cell proliferation and the
      cells' origin in idiopathic macular holes and to overcome the effects of
      embedding and sectioning preparation procedures on cell-distribution patterns.
      METHODS: Interference and phase-contrast microscopy, immunocytochemistry, and
      scanning and transmission electron microscopy were performed on surgically
      excised whole-mounted internal limiting membrane (ILM) specimens removed from 60
      eyes with idiopathic macular holes. Cell distribution and cell morphology were
      correlated with immunocytochemical staining characteristics. Twelve cell type
      specific antibodies were used to detect glial cells, hyalocytes, retinal pigment
      epithelial cells, retinal ganglion cells, and immune cells. Cell viability was
      analyzed. RESULTS: Epiretinal cell proliferation was found in all ILM specimens,
      irrespective of the stage of the macular hole. Cell density showed a broad
      variety. Immunocytochemistry frequently revealed simultaneous expression of
      GFAP/CD45, GFAP/CD64, GFAP/CD68, GFAP/CRALBP, and GFAP/CD90. Some cells presented
      with intracellular contractile filaments (anti-alphaSMA); others were not
      immunoreactive to any antibody examined. The percentage of viable cells showed a
      broad variety with a mean of 73% (SD 29%). Electron microscopy demonstrated glial
      cells, hyalocytes, and myofibroblast-like cells. CONCLUSIONS: The presence of
      epiretinal cells at the ILM in all macular hole stages strongly suggests a
      substantial involvement of cell migration and proliferation in the course of
      macular hole development. Glial cells and hyalocytes play the predominant role in
      epiretinal cell proliferation. Given the co-expression of glial cell and
      hyalocyte markers, transdifferentiation of epiretinal cells needs further
      elucidation, especially with respect to alphaSMA-positive cells leading to
      traction at the vitreoretinal interface.

PMID- 21900376
TI  - Amelioration of experimental autoimmune uveoretinitis by aldose reductase
      inhibition in Lewis rats.
AB  - PURPOSE: Recently, the authors showed that the inhibition of aldose reductase
      (AR) prevents bacterial endotoxin-induced uveitis in rats. They have now
      investigated the efficacy of AR inhibitors in the prevention of experimental
      autoimmune-induced uveitis (EAU) in rats. METHODS: Lewis rats were immunized with
      bovine interphotoreceptor retinoid-binding peptide (IRBP) to develop EAU. Two or
      8 days after immunization, the rats started receiving the AR inhibitor fidarestat
      (7 mg/kg/d; intraperitoneally). They were killed when the disease was at its
      peak; aqueous humor (AqH) was collected from one eye, and the other eye of each
      rat was used for histologic studies. The protein concentration and the levels of
      inflammatory markers were determined in AqH. Immunohistochemical analysis of eye
      sections was performed to determine the expression of inflammatory markers. The
      effect of AR inhibition on immune response was investigated in isolated T
      lymphocytes. RESULTS: Immunization of rats by IRBP peptide resulted in a
      significant infiltration of leukocytes in the posterior and the anterior chambers
      of the eye. Further, EAU caused an increase in the concentration of proteins,
      inflammatory cytokines, and chemokines in AqH, and the expression of inflammatory
      markers such as inducible-nitric oxide synthase and cycloxygenase-2 in the rat
      eye ciliary bodies and retina. Treatment with fidarestat significantly prevented
      the EAU-induced ocular inflammatory changes. AR inhibition also prevented the
      proliferation of spleen-derived T cells isolated from EAU rats in response to the
      IRBP antigen. CONCLUSIONS: These results suggest that AR could be a novel
      mediator of bovine IRBP-induced uveitis in rats.

PMID- 21900377
TI  - Residual electroretinograms in young Leber congenital amaurosis patients with
      mutations of AIPL1.
AB  - PURPOSE: To describe in detail the clinical phenotype and electrophysiological
      features of three patients with Leber congenital amaurosis caused by mutations of
      AIPL1. METHODS: Ophthalmologic examination, color fundus photography, detailed
      electrophysiological assessment, and screening of AIPL1 were undertaken in three
      subjects. One patient also underwent visual field testing and spectral domain
      optical coherence tomography. RESULTS: All three patients, two of whom were
      siblings, had histories consistent with Leber congenital amaurosis (severely
      reduced vision, poorly responsive pupils, and nystagmus presenting within the
      first year of life). However, each patient had recordable and similar
      electroretinograms (ERGs), which demonstrated absent cone-driven responses and
      slow insensitive scotopic responses. The first patient was found to have a
      homozygous Trp278 stop mutation in AIPL1, whereas the siblings were each found to
      have novel heterozygous mutations in AIPL1 (Leu17Pro and Lys214Asn). CONCLUSIONS:
      Patients with mutations in AIPL1 may present with Leber congenital amaurosis and
      residual ERGs characterized by slow insensitive scotopic responses. Such
      responses are likely seen only in very young patients and may not be seen with
      the typical filter settings recommended by the ISCEV standards because of low
      pass filtering. Progressive loss of residual ERG activity in young LCA patients
      with AIPL1 mutations suggests that gene replacement therapy will likely have to
      be performed early.

PMID- 21900378
TI  - Telomere length and telomerase reverse transcriptase gene copy number in patients
      with papillary thyroid carcinoma.
AB  - CONTEXT: The family risk ratio for papillary thyroid carcinoma (PTC) is among the
      highest of all cancers. Collectively, familial cases (fPTC) and sporadic cases
      (sPTC) are not known to show molecular differences. However, one study reported
      that telomeres were markedly shorter and the telomerase reverse transcriptase
      (TERT) gene was amplified and up-regulated in germline DNA from patients with
      fPTC compared with sPTC. OBJECTIVE: The aim of this study was to evaluate
      telomere length and TERT gene amplification and expression in blood samples of
      fPTC and sPTC patients in a genetically distinct population from the previous
      study. DESIGN: In 42 fPTC and 65 sPTC patients, quantitative real-time PCR was
      employed to measure the relative telomere length (RTL) and TERT gene copy number
      and RNA level. To validate the results using alternative methods, we further
      studied a subset of the original cohort consisting of randomly chosen fPTC (n =
      10) and sPTC (n = 14) patients and controls (n = 21) by assessing both telomere
      length by flow fluorescent in situ hybridization and TERT gene expression by
      quantitative real-time PCR. RESULTS: RTL and TERT gene copy number did not differ
      between fPTC and sPTC (P = 0.957 and P = 0.998, respectively). The mean RTL and
      TERT gene expression were not significantly different among the groups of the
      validation series (P = 0.169 and P = 0.718, respectively). CONCLUSION: Our data
      show no difference between familial and sporadic PTC with respect to telomere
      length, TERT copy number, or expression in our cohort. Further investigations in
      additional cohorts of patients are desirable.

PMID- 21900379
TI  - Circulating clusterin (apolipoprotein J) levels do not have any day/night
      variability and are positively associated with total and LDL cholesterol levels
      in young healthy individuals.
AB  - CONTEXT: Clusterin has been associated with several pathologies, including
      cardiovascular disease and neoplasias. However, little is known about its
      physiology and its association with metabolic and anthropometric parameters in
      humans. OBJECTIVE: The aim of the study was to examine whether circulating
      clusterin levels exhibit a day/night variation pattern and whether clusterin is
      associated with anthropometric and metabolic parameters. DESIGN: Study A was a
      frequent sampling study to evaluate potential periodicity in clusterin secretion.
      Study B was an observational study to evaluate the cross-sectional and
      prospective associations of clusterin with anthropometric and metabolic
      parameters. PARTICIPANTS: Study A participants were healthy males (n = 6) and
      females (n = 6), aged 22.3 +/- 3.1 and 22.8 +/- 3.4 yr, respectively. Study B
      participants were 186 healthy males aged 18.4 +/- 0.14 yr. Ninety-one of the
      study B subjects were studied again 2 yr later and clusterin's associations with
      change of anthropometric and metabolic parameters were thus investigated
      prospectively. INTERVENTION: Samples in study A were collected every 15 min
      during an overnight admission, and subsequently pooled every hour. Samples in
      study B were collected during a screening visit. MAIN OUTCOME MEASURE:
      Circulating clusterin levels were measured. RESULTS: In study A, spectral domain
      and cosinor regression analysis failed to reveal any day/night variation pattern.
      In study B, clusterin was positively correlated with total and low-density
      lipoprotein cholesterol (r = 0.23, P = 0.002; and r = 0.20, P = 0.005). Baseline
      clusterin did not predict change of any anthropometric, biochemical, or metabolic
      parameters prospectively. CONCLUSIONS: We report for the first time that
      circulating clusterin does not have a day/night variation pattern in healthy
      young individuals. Clusterin levels are associated with total and low-density
      lipoprotein cholesterol cross-sectionally but do not predict short-term changes
      in metabolic parameters in healthy young males.

PMID- 21900380
TI  - Postnatal developmental changes in the pituitary-ovarian axis in preterm and term
      infant girls.
AB  - CONTEXT: Postnatal pituitary-testicular activation in infant boys is well
      characterized. However, the ovarian response to pituitary activation in infancy
      is less well understood. OBJECTIVE: The aim of the study was to compare postnatal
      developmental changes in the pituitary-ovarian axis in preterm and term infant
      girls. PARTICIPANTS AND DESIGN: Sixty-three infant girls, divided into three
      groups according to gestational age (GA) [i.e. full term (FT; n = 29; GA, 37-42
      wk), near term (NT; n = 17; GA, 34-37 wk), and preterm (PT; n = 17; GA, 24-34
      wk)] were examined monthly from 1 wk (D7) to 6 months (M1-M6) of age and
      reexamined at the corrected age of 14 months (cM14). MAIN OUTCOME MEASURES: We
      performed a longitudinal follow-up of urinary FSH and serum anti-Mullerian
      hormone (AMH) levels and the number of follicles in transabdominal ovarian
      ultrasonography. RESULTS: The postnatal FSH surge was stronger and more prolonged
      in NT and PT girls than in FT girls (P <= 0.001). Increased folliculogenesis and
      a rise in AMH levels were observed in all three groups after the FSH surge. In NT
      and PT girls, follicular development was delayed in comparison with FT girls, and
      a decrease in high FSH levels around the 40th postmenstrual week was temporally
      associated with the appearance of antral follicles in ultrasonography and an
      increase in AMH levels. CONCLUSIONS: The postnatal FSH surge results in transient
      ovarian stimulation in term and preterm girls. A delay in ovarian
      folliculogenesis shown in ovarian ultrasonography and by low serum AMH levels may
      provide an explanation for the exaggerated FSH surge in NT and PT girls.

PMID- 21900381
TI  - Weight beneficial treatments for type 2 diabetes.
AB  - CONTEXT: The close link between type 2 diabetes and excess body weight highlights
      the need to consider the weight effects of different treatment regimens. We
      examine the impact of "weight-friendly" type 2 diabetes pharmacotherapies and
      suggest treatment strategies that mitigate weight gain. EVIDENCE ACQUISITION:
      Evidence was identified via PubMed search by class and agent and in
      bibliographies of review articles, with final articles for inclusion selected by
      author consensus. EVIDENCE SYNTHESIS: Substantial evidence confirms the weight
      benefits of metformin and shows that, of the newer available agents, glucagon
      like peptide-1 (GLP-1) agonists and amylin analogs promote weight loss.
      Dipeptidyl peptidase-4 (DPP-4) inhibitors and bile acid sequestrants are weight
      neutral. Liraglutide and exenatide appear to have similar effects on weight;
      however, recent research suggests a potentially greater effect of liraglutide on
      glycemic control compared to exenatide, when used as a second-line therapy.
      Mounting evidence suggests that insulin detemir may provide the most favorable
      weight benefits of available insulins. CONCLUSIONS: Weight-beneficial agents
      should be considered in patients, particularly obese patients, who fail to reach
      glycemic targets on metformin therapy. We propose the following treatment choices
      based on potential weight benefit and blood glucose increment: long-acting GLP-1
      agonists (liraglutide), DPP-4 inhibitors, bile acid sequestrants, amylin analogs,
      and basal insulin for patients with elevated fasting plasma glucose; and short
      acting (exenatide) or long-acting GLP-1 agonists, amylin analogs, DPP-4
      inhibitors, acarbose, and bile acid sequestrants for patients with elevated
      postprandial glucose. The weight-sparing effects of insulin detemir, notably in
      patients with high body mass index, should also be considered when initiating
      insulin therapy.

PMID- 21900382
TI  - The growth hormone receptor (GHR) c.899dupC mutation functions as a dominant
      negative: insights into the pathophysiology of intracellular GHR defects.
AB  - CONTEXT: GH insensitivity (GHI) is a condition characterized by pronounced IGF-I
      deficiency and severe short stature. We previously identified a novel compound
      heterozygous GH receptor (GHR) mutation, GHR:p.R229H/c.899dupC, in a patient
      presenting with GHI. The heterozygous p.R229H (prepeptide) variant was previously
      associated with GHI despite a lack of adequate functional studies. The novel
      heterozygous GHR:c.899dupC variant affects the critical JAK2-binding Box 1 region
      of the GHR intracellular domain; the duplication predicted a frameshift and early
      protein termination. OBJECTIVE: The individual and synergistic effect(s) of the
      p.R229H and c.899dupC mutations on GHR function(s) were evaluated in
      reconstitution studies. RESULTS: The recombinant human GHR (hGHR):p.R229H variant
      was readily expressed, and unexpectedly, GH-induced signal transducer and
      activator of transcription 5b (STAT5b) phosphorylation was comparable to that
      induced by wild-type hGHR. The truncated, immunodetected hGHR:c.899dupC variant,
      in contrast, was unresponsive to GH. To mimic a compound heterozygous state, the
      two variants were coexpressed, and strikingly, the presence of the hGHR:c.899dupC
      effectively abolished the GH-induced STAT5b activities that were observed with
      hGHR:p.R229H alone. Furthermore, hGHR:c.899dupC dose-dependently reduced the GH
      induced STAT5b activities associated with hGHR:p.R229H. This dominant negative
      effect was also observed when hGHR:c.899dupC was coexpressed with wild-type hGHR.
      CONCLUSION: The p.R229H variant, contrary to an earlier report, appeared to
      function like wild-type GHR and, therefore, is unlikely to cause GHI. The
      c.899dupC variant is a novel dominant negative mutation that disrupted normal GHR
      signaling and is the cause for the GHI phenotype of the reported patient.

PMID- 21900383
TI  - Molecular basis of thyroid dyshormonogenesis: genetic screening in population
      based Japanese patients.
AB  - CONTEXT: Inborn errors of thyroid hormone biosynthesis are collectively referred
      to as thyroid dyshormonogenesis (DH). Seven genes have been implicated in DH,
      including the dual oxidase 2 gene (DUOX2), the thyroglobulin gene (TG), and the
      thyroid peroxidase gene (TPO). OBJECTIVE: We aimed to define the prevalence and
      phenotypic spectrum of DH with single gene mutations. SUBJECTS AND METHODS: A
      population-based cohort of 102 patients with permanent congenital hypothyroidism
      was enrolled. Fourteen were diagnosed as DH and were analyzed for the seven
      causative genes including DUOX2, TG, and TPO. Several common mutations were
      screened in the remaining 88 patients. Pathogenicity of single amino acid
      mutations was verified in vitro. RESULTS: We identified four, five, and two
      patients with seemingly biallelic mutations in DUOX2, TG, and TPO, respectively.
      We also found two patients having one heterozygous DUOX2 mutation and one
      uncommon single-nucleotide polymorphism (SNP) p.H678R (rs57659670, allele
      frequency 0.035) and another two patients with homozygous p.H678R. Expression
      experiments and RT-PCR revealed that p.H678R is a functional SNP with theoretical
      40% loss of function, supporting a role of p.H678R in the onset of DH. As for
      clinical phenotypes, patients with inactive DUOX2 alleles (mutations and/or
      p.H678R) showed characteristic time-dependent improvement of thyroid function and
      morphology. All three evaluated patients had a negative result in the perchlorate
      test. CONCLUSIONS: Mutations (or a functional SNP) in DUOX2, TG, or TPO were
      observed in 93% (95% confidence interval = 70-99%) of DH patients. Inactive DUOX2
      alleles cause a broader phenotypic spectrum than currently accepted.

PMID- 21900384
TI  - Proximal promoter of the cytochrome P450 oxidoreductase gene: identification of
      microdeletions involving the untranslated exon 1 and critical function of the SP1
      binding sites.
AB  - CONTEXT: POR (cytochrome P450 oxidoreductase) is a ubiquitously expressed gene
      encoding an electron donor to all microsomal P450 enzymes and several non-P450
      enzymes. POR mutations cause an autosomal recessive disorder characterized by
      skeletal dysplasia, adrenal dysfunction, and disorders of sex development.
      Although recent studies have indicated the presence of a CpG-rich region
      characteristic of housekeeping genes around the untranslated exon 1 (exon 1U) and
      a tropic effect of thyroid hormone on POR expression via thyroid hormone receptor
      beta, detailed regulatory mechanisms for the POR expression remain to be
      clarified. OBJECTIVE: Our objective was to report a pivotal element of the
      proximal promoter of POR. RESULTS: We first studied three patients (cases 1-3)
      with POR deficiency due to compound heterozygosity with an p.R457H mutation and
      transcription failure of an apparently normal allele, by oligoarray comparative
      genomic hybridization and serial direct sequencing of the deletion fusion points.
      Consequently, a 2,487-bp microdeletion involving exon 1U was identified in case 1
      and an identical 49,604-bp deletion involving exon 1U and exon 1 was found in
      cases 2 and 3. We next analyzed the 2,487-bp region commonly deleted in cases 1-3
      by in silico analysis, DNA binding analysis, luciferase assays, and methylation
      analysis. The results showed a critical function of the evolutionally conserved
      SP1 binding sites just upstream of exon 1U, especially the binding site at the
      position -26/-17, in the transcription of POR. CONCLUSIONS: The results suggest
      that the SP1 binding sites constitute an essential element of the POR proximal
      promoter.

PMID- 21900385
TI  - Pancreatic ductal and acinar cell neoplasms in Carney complex: a possible new
      association.
AB  - CONTEXT: Carney complex (CNC) is a rare disease inherited as an autosomal
      dominant trait, associated with various tumors, and caused most frequently by
      inactivation of the PRKAR1A gene. OBJECTIVES: In our recent investigation of a
      large cohort of CNC patients, we identified several cases of pancreatic
      neoplasms. This possible association and PRKAR1A's possible involvement in
      pancreatic tumor have not been reported previously. PATIENTS AND METHODS: Nine
      patients (2.5%) with CNC and pancreatic neoplasms in an international cohort of
      354 CNC patients were identified; we studied six of them. Immunohistochemistry
      and PRKAR1A sequencing were obtained. RESULTS: Three men and three women with a
      mean age of 49 yr (range 34-75 yr) had acinar cell carcinoma (n = 2),
      adenocarcinoma (n = 1), and intraductal pancreatic mucinous neoplasm (n = 3).
      Five patients had a germline PRKAR1A mutation, including two patients with acinar
      cell carcinoma, for whom mutations were found in a hemizygous state in the tumor,
      suggesting loss of heterozygosity. PRKAR1A expression was not detected in five of
      the six pancreatic neoplasms from CNC patients, whereas the protein was amply
      expressed on other sporadic pancreatic tumors and normal tissue. CONCLUSION: An
      unexpectedly high prevalence of rare pancreatic tumors was found among CNC
      patients. Immunohistochemistry and loss-of-heterozygosity studies suggest that
      PRKAR1A could function as a tumor suppressor gene in pancreatic tissue, at least
      in the context of CNC. Clinicians taking care of CNC patients should be aware of
      the possible association of CNC with a potentially aggressive pancreatic
      neoplasm.

PMID- 21900386
TI  - The expression and pathophysiological role of osteopontin in Graves' disease.
AB  - CONTEXT: Graves' disease (GD) is a common autoimmune disease that affects the
      thyroid gland. Its pathogenesis is tightly involved with aberrant proinflammatory
      cytokine production. Osteopontin (OPN), an extracellular matrix protein of
      pleiotropic properties, has recently been recognized as a potent inflammatory
      cytokine in several autoimmune diseases. OBJECTIVE: This study sought to explore
      the pathophysiological role of OPN in GD by comparing OPN levels in initial GD
      patients and healthy controls. METHODS: Seventy-six patients who met criteria for
      initial GD and sixty-five healthy controls were recruited. OPN and other clinical
      GD diagnosis parameters were measured. In addition, the coexpression of several
      OPN receptors as well as various nuclear factor-kappaB (NF-kappaB) downstream
      target genes were examined in peripheral blood mononuclear cells from human
      subjects. The effect of OPN on NF-kappaB activation was determined by in vitro
      assays. RESULTS: We demonstrated for the first time that the OPN levels are
      enhanced in serum from GD patients. OPN levels are strongly associated with
      clinical serum parameters for GD diagnosis. The coexpression of selective OPN
      receptors and inflammatory response genes was enhanced in peripheral blood
      mononuclear cells from GD patients. Furthermore, serum from GD patients activated
      NF-kappaB activity in vitro, which was significantly suppressed by OPN monoclonal
      antibody abrogation. CONCLUSION: These data indicated a clinical correlation
      between serum OPN levels and GD. OPN could affect GD development through NF
      kappaB activation and the subsequent changes in inflammatory milieu. OPN could
      serve as a novel biomarker for GD as well as a potential target for GD treatment.

PMID- 21900388
TI  - beta1-integrin: a potential therapeutic target in the battle against cancer
      recurrence.
AB  - Primary cancer treatment, involving both local and often systemic adjuvant
      therapy, is often successful, especially if the cancer is detected at an early
      stage of progression. However, for some patients, the cancer may recur either
      locally or as distant metastases, in some cases many years after apparently
      successful primary treatment. Significant tumor dormancy has been documented in
      several cancers, such as breast, melanoma, and renal cancer. Tumor dormancy has
      long been recognized as an important problem in management of cancer patients.
      Recent work has clarified biologic aspects of tumor dormancy and has shown that
      dormant tumor cells may be resistant to cytotoxic chemotherapy and radiation.
      This work has led to recognition of a key role for beta1-integrin in regulating
      the switch from a dormant state to active proliferation and metastasis. Here we
      discuss the role of beta1-integrin and its signaling partners in regulating the
      dormant phenotype. We also consider possible therapeutic approaches, such as
      small molecules or antibodies (ATN-161, volociximab, and JSM6427), directed
      against beta1-integrin signaling to target dormant cancer cells and to prevent
      metastatic recurrence.

PMID- 21900387
TI  - A metabolomic and systems biology perspective on the brain of the fragile X
      syndrome mouse model.
AB  - Fragile X syndrome (FXS) is the first cause of inherited intellectual disability,
      due to the silencing of the X-linked Fragile X Mental Retardation 1 gene encoding
      the RNA-binding protein FMRP. While extensive studies have focused on the
      cellular and molecular basis of FXS, neither human Fragile X patients nor the
      mouse model of FXS--the Fmr1-null mouse--have been profiled systematically at the
      metabolic and neurochemical level to provide a complementary perspective on the
      current, yet scattered, knowledge of FXS. Using proton high-resolution magic
      angle spinning nuclear magnetic resonance ((1)H HR-MAS NMR)-based metabolic
      profiling, we have identified a metabolic signature and biomarkers associated
      with FXS in various brain regions of Fmr1-deficient mice. Our study highlights
      for the first time that Fmr1 gene inactivation has profound, albeit coordinated
      consequences in brain metabolism leading to alterations in: (1) neurotransmitter
      levels, (2) osmoregulation, (3) energy metabolism, and (4) oxidative stress
      response. To functionally connect Fmr1-deficiency to its metabolic biomarkers, we
      derived a functional interaction network based on the existing knowledge
      (literature and databases) and show that the FXS metabolic response is initiated
      by distinct mRNA targets and proteins interacting with FMRP, and then relayed by
      numerous regulatory proteins. This novel "integrated metabolome and interactome
      mapping" (iMIM) approach advantageously unifies novel metabolic findings with
      previously unrelated knowledge and highlights the contribution of novel cellular
      pathways to the pathophysiology of FXS. These metabolomic and integrative systems
      biology strategies will contribute to the development of potential drug targets
      and novel therapeutic interventions, which will eventually benefit FXS patients.

PMID- 21900389
TI  - Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma.
AB  - Ipilimumab (MDX-010, Yervoy; Bristol-Myers Squibb), a fully human monoclonal
      antibody against CTL antigen 4 (CTLA-4), was recently approved by the U.S. Food
      and Drug Administration (FDA) for the treatment of metastatic melanoma. In both
      early- and late-phase trials, ipilimumab has shown consistent activity against
      melanoma. For example, in a randomized phase III trial that enrolled patients
      with previously treated metastatic disease, ipilimumab, with or without a peptide
      vaccine, improved overall survival: Median overall survival was 10.1 and 10.0
      months in the ipilimumab and ipilimumab plus vaccine arms, respectively, versus
      6.4 months in the vaccine-alone group (hazard ratio, 0.68; P <= 0.003). Serious
      (grade 3-5) immune-related adverse events occurred in 10% to 15% of patients.
      Thus, although it provides a clear survival benefit, ipilimumab administration
      requires careful patient monitoring and sometimes necessitates treatment with
      immune-suppressive therapy. Here, we review the mechanism of action, preclinical
      data, and multiple clinical trials that led to FDA approval of ipilimumab for
      metastatic melanoma.

PMID- 21900390
TI  - Role of BRAF in thyroid oncogenesis.
AB  - BRAF, a cytoplasmic serine-threonine protein kinase, plays a critical role in
      cell signaling as an activator within the mitogen-activated protein kinase (MAPK)
      pathway. The most common BRAF mutation is the V600E transversion, which causes
      constitutive kinase activity. This mutation has been found in a multitude of
      human cancers, including both papillary thyroid cancer (PTC) and papillary
      derived anaplastic thyroid cancer (ATC), in which it initiates follicular cell
      transformation. With such a high frequency of BRAF mutations in PTC (44%) and PTC
      derived ATC (24%), research in BRAF(V600E) detection for diagnostic purposes has
      shown high sensitivity and specificity for tumor cell presence. BRAF(V600E) in
      PTC has also provided valuable prognostic information, as its presence has been
      correlated with more aggressive and iodine-resistant phenotypes. Such findings
      have initiated research in targeting oncogenic BRAF in cancer therapeutics.
      Although multiple phase II clinical trials in patients with iodine-refractory
      metastatic PTC have shown significant efficacy for sorafenib, a first-generation
      BRAF inhibitor, the mechanism by which it mediates its effect remains unclear
      because of multiple additional kinase targets of sorafenib. Additionally,
      preclinical and clinical studies investigating combination therapy with agents
      such as selective (PLX 4032) and potent (BAY 73-4506 and ARQ 736) small-molecule
      BRAF inhibitors and MAP/extracellular signal-regulated kinase (ERK) kinase
      inhibitors (AZD6244) hold great promise in the treatment of BRAF(V600E) cancers
      and may eventually play a powerful role in changing the clinical course of PTC
      and ATC.

PMID- 21900391
TI  - A novel mutation of HOXA10 in a Chinese woman with a Mullerian duct anomaly.
AB  - BACKGROUND: Mullerian duct anomalies consist of a set of congenital structural
      malformations that occur when the Mullerian ducts do not develop properly during
      embryonic life. Their molecular genetic basis is poorly understood. METHODS: In
      this study, we conducted mutation analysis of the HOXA10 gene in a cohort of 109
      Chinese women with Mullerian duct anomalies. RESULTS: We identified a novel
      mutation (Y57C) in one patient with a didelphic uterus. The mutation affected the
      transcriptional regulation capacity of HOXA10. CONCLUSIONS: Our study showed that
      mutation of HOXA10 gene may contribute to the development of Mullerian duct
      anomalies and confirmed that HOXA10 is an important transcription factor in
      reproductive tract development.

PMID- 21900392
TI  - Progesterone and spermatozoa: a long-lasting liaison comes to definition.

PMID- 21900393
TI  - Catastrophizing: a predictor of persistent pain among women with endometriosis at
      1 year.
AB  - BACKGROUND: Endometriosis is the most common gynecological diagnosis among women
      with chronic pelvic pain, but the underlying mechanisms of endometriosis
      associated chronic pelvic pain remain unclear. Therefore, the objective of this
      study was to determine the biopsychosocial predictors of pain improvement among
      women with endometriosis. METHODS: One hundred and fifteen women who presented
      for treatment of endometriosis-associated chronic pelvic pain at a tertiary
      referral center at a university-based hospital participated in this prospective
      observational study of clinical practice. Participants completed questionnaires
      assessing pain, mental health and catastrophizing at entry and 1 year follow-up.
      The main outcome measure assessed was the interval change in pain report using
      the McGill pain 1uestionnaire. RESULT(S): On average, participants experienced a
      37.4% reduction in interval pain (P < 0.001). Adjusted for baseline pain,
      nulliparity (P = 0.002) and catastrophizing (P = 0.04) were associated with
      decreased probability of interval improvement in pain. Those referred for
      physical therapy had less interval pain improvement (P = 0.04). However,
      undergoing hysterectomy was a strong predictor of improvement in pain (P =
      0.008). CONCLUSION(S): Our study suggests that chronic pain in endometriosis may
      be more akin to other idiopathic pain disorders. Specifically, biopsychosocial
      variables, such as catastrophizing, play an important role in reported severity.
      Further research on biopsychosocial correlates of chronic pelvic pain in
      endometriosis is warranted.

PMID- 21900394
TI  - Tumor-associated macrophages mediate immunosuppression in the renal cancer
      microenvironment by activating the 15-lipoxygenase-2 pathway.
AB  - Renal cell carcinoma (RCC), the most common human kidney cancer, is frequently
      infiltrated with tumor-associated macrophages (TAM) that can promote malignant
      progression. Here, we show that TAMs isolated from human RCC produce substantial
      amounts of the proinflammatory chemokine CCL2 and immunosuppressive cytokine IL
      10, in addition to enhanced eicosanoid production via an activated 15
      lipoxygenase-2 (15-LOX2) pathway. TAMs isolated from RCC tumors had a high 15
      LOX2 expression and secreted substantial amounts of 15(S)-hydroxyeicosatetraenoic
      acid, its major bioactive lipid product. Inhibition of lipoxygenase activity
      significantly reduced production of CCL2 and IL-10 by RCC TAMs. In addition, TAMs
      isolated from RCC were capable of inducing in T lymphocytes, the pivotal T
      regulatory cell transcription factor forkhead box P3 (FOXP3), and the inhibitory
      cytotoxic T-lymphocyte antigen 4 (CTLA-4) coreceptor. However, this TAM-mediated
      induction of FOXP3 and CTLA-4 in T cells was independent of lipoxygenase and
      could not be reversed by inhibiting lipoxygenase activity. Collectively, our
      results show that TAMs, often present in RCCs, display enhanced 15-LOX2 activity
      that contributes to RCC-related inflammation, immunosuppression, and malignant
      progression. Furthermore, we show that TAMs mediate the development of immune
      tolerance through both 15-LOX2-dependent and 15-LOX2-independent pathways. We
      propose that manipulating LOX-dependent arachidonic acid metabolism in the tumor
      microenvironment could offer new strategies to block cancer-related inflammation
      and immune escape in patients with RCC.

PMID- 21900395
TI  - IRF-1 expression is essential for natural killer cells to suppress metastasis.
AB  - IFN-gamma promotes tumoral immune surveillance, but its involvement in
      controlling metastases is less clear. Using a mouse model of pulmonary
      metastases, we show that local IFN-gamma treatment inhibits formation of
      metastases through its regulation of IRF-1 in tumor cells. IRF-1 is an IFN-gamma
      induced transcription factor pivotal in the regulation of infection and
      inflammation. IRF-1 blockade abolished the inhibitory effect of IFN-gamma on
      tumor metastases, whereas ectopic expression of IRF-1 phenocopied the inhibitory
      effects of IFN-gamma. IRF-1 did not affect the survival of tumor cells in the
      circulation or their infiltration into lungs, but it was essential to support the
      pulmonary attraction and activation of natural killer (NK) cells. Depleting NK
      cells from mice abolished the protective effect of IFN-gamma or IRF-1 on
      metastases. In addition, cytotoxicity assays revealed that tumor cells expressing
      IRF-1 were targeted more effectively by NK cells than IRF-1 nonexpressing tumor
      cells. Moreover, NK cells isolated from lungs inoculated with IRF-1-expressing
      tumor cells exhibit a greater cytotoxic activity. Mechanistic investigations
      revealed that IRF-1-induced NK cell cytotoxicity was independent of perforin and
      granzyme B but dependent on the NK cell activating receptor DNAM-1. Taken
      together, our findings establish IRF-1 as an essential mediator of the cross-talk
      between tumor cells and NK cells that mediate immune surveillance in the
      metastatic niche.

PMID- 21900396
TI  - Human cytomegalovirus US28 found in glioblastoma promotes an invasive and
      angiogenic phenotype.
AB  - Human cytomegalovirus (HCMV) infections are seen often in glioblastoma multiforme
      (GBM) tumors, but whether the virus contributes to GBM pathogenesis is unclear.
      In this study, we explored an oncogenic role for the G-protein-coupled receptor
      like protein US28 encoded by HCMV that we found to be expressed widely in human
      GBMs. Immunohistochemical and reverse transcriptase PCR approaches established
      that US28 was expressed in approximately 60% of human GBM tissues and primary
      cultures examined. In either uninfected GBM cells or neural progenitor cells,
      thought to be the GBM precursor cells, HCMV infection or US28 overexpression was
      sufficient to promote secretion of biologically active VEGF and to activate
      multiple cellular kinases that promote glioma growth and invasion, including
      phosphorylated STAT3 (p-STAT3) and endothelial nitric oxide synthase (e-NOS).
      Consistent with these findings, US28 overexpression increased primary GBM cell
      invasion in Matrigel. Notably, this invasive phenotype was further enhanced by
      exposure to CCL5/RANTES, a US28 ligand, associated with poor patient outcome in
      GBM. Conversely, RNA interference-mediated knockdown of US28 in human glioma
      cells persistently infected with HCMV led to an inhibition in VEGF expression and
      glioma cell invasion in response to CCL5 stimulation. Analysis of clinical GBM
      specimens further revealed that US28 colocalized in situ with several markers of
      angiogenesis and inflammation, including VEGF, p-STAT3, COX2, and e-NOS. Taken
      together, our results indicate that US28 expression from HCMV contributes to GBM
      pathogenesis by inducing an invasive, angiogenic phenotype. In addition, these
      findings argue that US28-CCL5 paracrine signaling may contribute to glioma
      progression and suggest that targeting US28 may provide therapeutic benefits in
      GBM treatment.

PMID- 21900397
TI  - STAT3 is necessary for proliferation and survival in colon cancer-initiating
      cells.
AB  - STAT3 is constitutively activated in colon cancer but its contributions in cancer
      initiating cells have not been explored. In this study, we characterized STAT3 in
      aldehyde dehydrogenase (ALDH)-positive (ALDH(+)) and CD133-positive (CD133(+))
      subpopulations of human colon tumor cells that exhibited more potent tumor
      initiating ability than ALDH(-)/CD133(-) cells in tumor xenograft assays in mice.
      We found that ALDH(+)/CD133(+) cells expressed higher levels of the active
      phosphorylated form of STAT3 than either ALDH(-)/CD133(-) or unfractionated colon
      cancer cells. STAT3 inhibition by RNA interference-mediated knockdown or small
      molecule inhibitors LLL12 or Stattic blocked downstream target gene expression,
      cell viability, and tumorsphere-forming capacity in cancer-initiating cells.
      Similarly, treatment of mouse tumor xenografts with STAT3 short hairpin RNA
      (shRNA), interleukin 6 shRNA, or LLL12 inhibited tumor growth. Our results
      establish that STAT3 is constitutively activated in colon cancer-initiating cells
      and that these cells are sensitive to STAT3 inhibition. These findings establish
      a powerful rationale to develop STAT3 inhibitory strategies for treating advanced
      colorectal cancers.

PMID- 21900398
TI  - From mice and men to earth and space: joint NASA-NCI workshop on lung cancer risk
      resulting from space and terrestrial radiation.
AB  - On June 27-28, 2011, scientists from the National Cancer Institute (NCI), NASA,
      and academia met in Bethesda to discuss major lung cancer issues confronting each
      organization. For NASA, available data suggest that lung cancer is the largest
      potential cancer risk from space travel for both men and women and quantitative
      risk assessment information for mission planning is needed. In space, the
      radiation risk is from high energy and charge (HZE) nuclei (such as Fe) and high
      energy protons from solar flares and not from gamma radiation. In contrast, the
      NCI is endeavoring to estimate the increased lung cancer risk from the potential
      widespread implementation of computed tomographic (CT) screening in individuals
      at high risk for developing lung cancer based on the National Lung Cancer
      Screening Trial (NLST). For the latter, exposure will be X-rays from CT scans
      from the screening (which uses "low-dose" CT scans) and also from follow-up scans
      used to evaluate abnormalities found during initial screening. Topics discussed
      included the risk of lung cancer arising after HZE particle, proton, and low-dose
      exposure to Earth's radiation. The workshop examined preclinical models,
      epidemiology, molecular markers, "omics" technology, radiobiology issues, and
      lung stem cells that relate to the development of lung cancer.

PMID- 21900399
TI  - Quantifying the role of angiogenesis in malignant progression of gliomas: in
      silico modeling integrates imaging and histology.
AB  - Gliomas are uniformly fatal forms of primary brain neoplasms that vary from low-
      to high-grade (glioblastoma). Whereas low-grade gliomas are weakly angiogenic,
      glioblastomas are among the most angiogenic tumors. Thus, interactions between
      glioma cells and their tissue microenvironment may play an important role in
      aggressive tumor formation and progression. To quantitatively explore how tumor
      cells interact with their tissue microenvironment, we incorporated the
      interactions of normoxic glioma cells, hypoxic glioma cells, vascular endothelial
      cells, diffusible angiogenic factors, and necrosis formation into a first
      generation, biologically based mathematical model for glioma growth and invasion.
      Model simulations quantitatively described the spectrum of in vivo dynamics of
      gliomas visualized with medical imaging. Furthermore, we investigated how
      proliferation and dispersal of glioma cells combine to induce increasing degrees
      of cellularity, mitoses, hypoxia-induced neoangiogenesis and necrosis, features
      that characterize increasing degrees of "malignancy," and we found that changes
      in the net rates of proliferation (rho) and invasion (D) are not always necessary
      for malignant progression. Thus, although other factors, including the
      accumulation of genetic mutations, can change cellular phenotype (e.g.,
      proliferation and invasion rates), this study suggests that these are not
      required for malignant progression. Simulated results are placed in the context
      of the current clinical World Health Organization grading scheme for studying
      specific patient examples. This study suggests that through the application of
      the proposed model for tumor-microenvironment interactions, predictable patterns
      of dynamic changes in glioma histology distinct from changes in cellular
      phenotype (e.g., proliferation and invasion rates) may be identified, thus
      providing a powerful clinical tool.

PMID- 21900400
TI  - Definition of a FoxA1 Cistrome that is crucial for G1 to S-phase cell-cycle
      transit in castration-resistant prostate cancer.
AB  - The enhancer pioneer transcription factor FoxA1 is a global mediator of steroid
      receptor (SR) action in hormone-dependent cancers. In castration-resistant
      prostate cancer (CRPC), FoxA1 acts as an androgen receptor cofactor to drive G2
      to M-phase cell-cycle transit. Here, we describe a mechanistically distinct SR
      independent role for FoxA1 in driving G1 to S-phase cell-cycle transit in CRPC.
      By comparing FoxA1 binding sites in prostate cancer cell genomes, we defined a
      codependent set of FoxA1-MYBL2 and FoxA1-CREB1 binding sites within the
      regulatory regions of the Cyclin E2 and E2F1 genes that are critical for CRPC
      growth. Binding at these sites upregulate the Cyclin E2 and Cyclin A2 genes in
      CRPC but not in earlier stage androgen-dependent prostate cancer, establishing a
      stage-specific role for this pathway in CRPC growth. Mechanistic investigations
      indicated that FoxA1, MYBL2, or CREB1 induction of histone H3 acetylation
      facilitated nucleosome disruption as the basis for codependent transcriptional
      activation and G1 to S-phase cell-cycle transit. Our findings establish FoxA1 as
      a pivotal driver of the cell-cycle in CRPC which promotes G1 to S-phase transit
      as well as G2 to M-phase transit through two distinct mechanisms.

PMID- 21900401
TI  - ARID1A, a factor that promotes formation of SWI/SNF-mediated chromatin
      remodeling, is a tumor suppressor in gynecologic cancers.
AB  - ARID1A (BAF250A) promotes the formation of SWI/SNF chromatin remodeling complexes
      containing BRG1 or BRM. It has emerged as a candidate tumor suppressor based on
      its frequent mutations in ovarian clear cell and endometrioid cancers and in
      uterine endometrioid carcinomas. Here, we report that restoring wild-type ARID1A
      expression in ovarian cancer cells that harbor ARID1A mutations is sufficient to
      suppress cell proliferation and tumor growth in mice, whereas RNA interference
      mediated silencing of ARID1A in nontransformed epithelial cells is sufficient to
      enhance cellular proliferation and tumorigenicity. Gene expression analysis
      identified several downstream targets of ARID1A including CDKN1A and SMAD3, which
      are well-known p53 target genes. In support of the likelihood that p53 mediates
      the effects of ARID1A on these genes, we showed that p53 was required and
      sufficient for their regulation by ARID1A. Furthermore, we showed that CDKN1A
      (encoding p21) acted in part to mediate growth suppression by ARID1A. Finally, we
      obtained evidence that the ARID1A/BRG1 complex interacted directly with p53 and
      that mutations in the ARID1A and TP53 genes were mutually exclusive in tumor
      specimens examined. Our results provide functional evidence in support of the
      hypothesis that ARID1A is a bona fide tumor suppressor that collaborates with p53
      to regulate CDKN1A and SMAD3 transcription and tumor growth in gynecologic
      cancers.

PMID- 21900402
TI  - Aberrant lipid metabolism in hepatocellular carcinoma revealed by plasma
      metabolomics and lipid profiling.
AB  - There has been limited analysis of the effects of hepatocellular carcinoma (HCC)
      on liver metabolism and circulating endogenous metabolites. Here, we report the
      findings of a plasma metabolomic investigation of HCC patients by
      ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of
      flight mass spectrometry (UPLC-ESI-QTOFMS), random forests machine learning
      algorithm, and multivariate data analysis. Control subjects included healthy
      individuals as well as patients with liver cirrhosis or acute myeloid leukemia.
      We found that HCC was associated with increased plasma levels of
      glycodeoxycholate, deoxycholate 3-sulfate, and bilirubin. Accurate mass
      measurement also indicated upregulation of biliverdin and the fetal bile acids
      7alpha-hydroxy-3-oxochol-4-en-24-oic acid and 3-oxochol-4,6-dien-24-oic acid in
      HCC patients. A quantitative lipid profiling of patient plasma was also conducted
      by ultraperformance liquid chromatography-electrospray ionization-triple
      quadrupole mass spectrometry (UPLC-ESI-TQMS). By this method, we found that HCC
      was also associated with reduced levels of lysophosphocholines and in 4 of 20
      patients with increased levels of lysophosphatidic acid [LPA(16:0)], where it
      correlated with plasma alpha-fetoprotein levels. Interestingly, when fatty acids
      were quantitatively profiled by gas chromatography-mass spectrometry (GC-MS), we
      found that lignoceric acid (24:0) and nervonic acid (24:1) were virtually absent
      from HCC plasma. Overall, this investigation illustrates the power of the new
      discovery technologies represented in the UPLC-ESI-QTOFMS platform combined with
      the targeted, quantitative platforms of UPLC-ESI-TQMS and GC-MS for conducting
      metabolomic investigations that can engender new insights into cancer
      pathobiology.

PMID- 21900403
TI  - Characterization of chemokines and adhesion molecules associated with T cell
      presence in tertiary lymphoid structures in human lung cancer.
AB  - De novo formation of tertiary lymphoid structures (TLS) has been described in
      lung cancers. Intratumoral TLS seem to be functional and are associated with a
      long-term survival for lung cancer patients, suggesting that they represent an
      activation site for tumor-specific T cells. Here, we characterized T-cell
      recruitment to TLS in human lung cancer to identify the adhesion molecules and
      chemoattractants orchestrating this migration. We found that most TLS T cells
      were CD62L+ and mainly of CD4+ memory phenotype, but naive T cells were highly
      enriched in these structures as compared with the rest of the tumor. A specific
      gene expression signature associated with T cell presence was identified in TLS,
      which included chemokines (CCL19, CCL21, CXCL13, CCL17, CCL22, and IL16),
      adhesion molecules (ICAM-2, ICAM-3, VCAM-1, and MAdCAM-1) and integrins (alphaL,
      alpha4, and alphaD). The presence of the corresponding receptors on TLS T cells
      was confirmed. Intratumoral PNAd+ high endothelial venules also were exclusively
      associated with TLS and colocalized with CD62L+ lymphocytes. Together, these data
      bring new insights into the T-cell recruitment to intratumoral TLS and suggest
      that blood T cell enter into TLS via high endothelial venules, which represent a
      new gateway for T cells to the tumor. Findings identify the molecules that
      mediate migration of tumor-specific T cells into TLS where T cell priming occurs,
      suggesting new strategies to enhance the efficacy of cancer immunotherapies.

PMID- 21900406
TI  - Can we ever stop imaging in surgically treated and radiotherapy-naive patients
      with non-functioning pituitary adenoma?
AB  - BACKGROUND: Non-functioning pituitary adenomas (NFAs) are slow-growing tumours
      with reported re-growth rates following surgical resection alone of up to 50% at
      10 years. Currently, the desired length of follow-up surveillance imaging in un
      irradiated patients is unclear. AIM: To clarify the timing of re-growth in
      patients with NFAs, treated solely by surgery without post-operative pituitary
      radiotherapy, and also to clarify whether continued imaging is necessary in these
      patients. METHODS: A case note analysis of all patients who underwent surgery
      alone for NFA between January 1984 and December 2007 was undertaken. Patients
      were followed for a minimum of 1 year. Re-growth was diagnosed on the basis of
      radiological appearances with or without associated manifestations. RESULTS: One
      hundred and fifty-five patients (94 males, mean age at diagnosis 57.9 (range 18.3
      88) years) were included. Twenty-nine were followed up for more than 10 years.
      The mean follow-up following surgery was 6.1 years (median 4.3 (range 1-25.8)).
      Re-growth was documented in 54 (34.8%) cases and 20.4% of these cases showed
      relapse/re-growth 10 or more years after the initial surgery. Kaplan-Meier
      analysis showed relapse rates of 23.1, 46.7 and 67.9% at 5, 10 and 15 years
      respectively. There was a significant increase in the re-growth rates if there
      was either pituitary tumour remnant observed on the first post-operative scan
      (P<=0.001) or a younger age at initial surgery (P=0.034). CONCLUSION: These
      results suggest that patients with NFAs need to be closely monitored following
      surgery, particularly those with post-operative tumour remnants. With 20% of
      relapse occurring after 10 years, follow-up surveillance needs to be continued
      beyond this time.

PMID- 21900405
TI  - Cross talk among TGF-beta signaling pathways, integrins, and the extracellular
      matrix.
AB  - The growth factor TGF-beta is secreted in a latent complex consisting of three
      proteins: TGF-beta, an inhibitor (latency-associated protein, LAP, which is
      derived from the TGF-beta propeptide) and an ECM-binding protein (one of the
      latent TGF-beta binding proteins, or LTBPs). LTBPs interact with fibrillins and
      other ECM components and thus function to localize latent TGF-beta in the ECM.
      LAP contains an integrin-binding site (RGD), and several RGD-binding integrins
      are able to activate latent TGF-beta through binding this site. Mutant mice
      defective in integrin-mediated activators, and humans and mice with fibrillin
      gene mutations, show the critical role of ECM and integrins in regulating TGF
      beta signaling.

PMID- 21900407
TI  - Adolescent risk behaviours and mealtime routines: does family meal frequency
      alter the association between family structure and risk behaviour?
AB  - Family structure is associated with a range of adolescent risk behaviours, with
      those living in both parent families generally faring best. This study describes
      the association between family structure and adolescent risk behaviours and
      assesses the role of the family meal. Data from the 2006 Health Behaviour in
      School-Aged Children survey were modelled using Multilevel Binomial modelling for
      six risk behaviour outcomes. Significantly more children from 'both parent'
      families ate a family meal every day and fewer 'hardly ever or never' did. Family
      structure was associated with boys' and girls' smoking, drinking, cannabis use
      and having sex and with girls' fighting. Frequency of eating a family meal was
      associated with a reduced likelihood of all risk behaviours among girls and all
      but fighting and having sex among boys. Eating a family meal regularly nullified
      the association between family structure and drinking alcohol for boys and girls
      and cannabis use for boys and reduced the effect size of alternative family
      structures on boys having sex and smoking. The family meal, associated with a
      reduced likelihood of many adolescent risk behaviours, reduces or eliminates the
      association with family structure and may therefore help to overcome inequalities
      in adolescent risk behaviours.

PMID- 21900408
TI  - Physical activity mass media campaigns and their evaluation: a systematic review
      of the literature 2003-2010.
AB  - Internationally, mass media campaigns to promote regular moderate-intensity
      physical activity have increased recently. Evidence of mass media campaign
      effectiveness exists in other health areas, however the evidence for physical
      activity is limited. The purpose was to systematically review the literature on
      physical activity mass media campaigns, 2003-2010. A focus was on reviewing
      evaluation designs, theory used, formative evaluation, campaign effects and
      outcomes. Literature was searched resulting in 18 individual adult mass media
      campaigns, mostly in high-income regions and two in middle-income regions.
      Designs included: quasi experimental (n = 5); non experimental (n = 12); a mixed
      methods design (n = 1). One half used formative research. Awareness levels ranged
      from 17 to 95%. Seven campaigns reported significant increases in physical
      activity levels. The review found that beyond awareness raising, changes in other
      outcomes were measured, assessed but reported in varying ways. It highlighted
      improvements in evaluation, although limited evidence of campaign effects remain.
      It provides an update on the evaluation methodologies used in the adult
      literature. We recommend optimal evaluation design should include: (1) formative
      research to inform theories/frameworks, campaign content and evaluation design;
      (2) cohort study design with multiple data collection points; (3) sufficient
      duration; (4) use of validated measures; (5) sufficient evaluation resources.

PMID- 21900404
TI  - Chemical and biological approaches for adapting proteostasis to ameliorate
      protein misfolding and aggregation diseases: progress and prognosis.
AB  - Maintaining the proteome to preserve the health of an organism in the face of
      developmental changes, environmental insults, infectious diseases, and rigors of
      aging is a formidable task. The challenge is magnified by the inheritance of
      mutations that render individual proteins subject to misfolding and/or
      aggregation. Maintenance of the proteome requires the orchestration of protein
      synthesis, folding, degradation, and trafficking by highly conserved/deeply
      integrated cellular networks. In humans, no less than 2000 genes are involved.
      Stress sensors detect the misfolding and aggregation of proteins in specific
      organelles and respond by activating stress-responsive signaling pathways. These
      culminate in transcriptional and posttranscriptional programs that up-regulate
      the homeostatic mechanisms unique to that organelle. Proteostasis is also
      strongly influenced by the general properties of protein folding that are
      intrinsic to every proteome. These include the kinetics and thermodynamics of the
      folding, misfolding, and aggregation of individual proteins. We examine a growing
      body of evidence establishing that when cellular proteostasis goes awry, it can
      be reestablished by deliberate chemical and biological interventions. We start
      with approaches that employ chemicals or biological agents to enhance the general
      capacity of the proteostasis network. We then introduce chemical approaches to
      prevent the misfolding or aggregation of specific proteins through direct binding
      interactions. We finish with evidence that synergy is achieved with the
      combination of mechanistically distinct approaches to reestablish organismal
      proteostasis.

PMID- 21900409
TI  - Why look backwards?

PMID- 21900410
TI  - Commentary on: Fatigue and extended work hours among perfusionists: 2010 Survey.

PMID- 21900411
TI  - Commentary on: 2010 Survey of cell phone use during cardiopulmonary bypass.

PMID- 21900416
TI  - Trauma exposure and posttraumatic stress disorder among employees of New York
      City companies affected by the September 11, 2001 attacks on the World Trade
      Center.
AB  - OBJECTIVE: Several studies have provided prevalence estimates of posttraumatic
      stress disorder (PTSD) related to the September 11, 2001 (9/11) attacks in
      broadly affected populations, although without sufficiently addressing qualifying
      exposures required for assessing PTSD and estimating its prevalence. A premise
      that people throughout the New York City area were exposed to the attacks on the
      World Trade Center (WTC) towers and are thus at risk for developing PTSD has
      important implications for both prevalence estimates and service provision. This
      premise has not, however, been tested with respect to DSM-IV-TR criteria for
      PTSD. This study examined associations between geographic distance from the 9/11
      attacks on the WTC and reported 9/11 trauma exposures, and the role of specific
      trauma exposures in the development of PTSD. METHODS: Approximately 3 years after
      the attacks, 379 surviving employees (102 with direct exposures, including 65 in
      the towers, and 277 with varied exposures) recruited from 8 affected
      organizations were interviewed using the Diagnostic Interview Schedule/Disaster
      Supplement and reassessed at 6 years. The estimated closest geographic distance
      from the WTC towers during the attacks and specific disaster exposures were
      compared with the development of 9/11-related PTSD as defined by the Diagnostic
      and Statistical Manual, Fourth Edition, Text Revision. RESULTS: The direct
      exposure zone was largely concentrated within a radius of 0.1 mi and completely
      contained within 0.75 mi of the towers. PTSD symptom criteria at any time after
      the disaster were met by 35% of people directly exposed to danger, 20% of those
      exposed only through witnessed experiences, and 35% of those exposed only through
      a close associate's direct exposure. Outside these exposure groups, few possible
      sources of exposure were evident among the few who were symptomatic, most of whom
      had preexisting psychiatric illness. CONCLUSIONS: Exposures deserve careful
      consideration among widely affected populations after large terrorist attacks
      when conducting clinical assessments, estimating the magnitude of population PTSD
      burdens, and projecting needs for specific mental health interventions.

PMID- 21900417
TI  - Trends in probable PTSD in firefighters exposed to the World Trade Center
      disaster, 2001-2010.
AB  - OBJECTIVE: We present the longest follow-up, to date, of probable posttraumatic
      stress disorder (PTSD) after the 2001 terrorist attacks on the World Trade Center
      (WTC) in New York City firefighters who participated in the rescue/recovery
      effort. METHODS: We examined data from 11,006 WTC-exposed firefighters who
      completed 40,672 questionnaires and reported estimates of probable PTSD by year
      from serial cross-sectional analyses. In longitudinal analyses, we used separate
      Cox models with data beginning from October 2, 2001, to identify variables
      associated with recovery from or delayed onset of probable PTSD. RESULTS: The
      prevalence of probable PTSD was 7.4% by September 11, 2010, and continued to be
      associated with early arrival at the WTC towers during every year of analysis. An
      increasing number of aerodigestive symptoms (hazard ratio [HR] 0.89 per symptom,
      95% confidence interval [CI] 0.86-.93) and reporting a decrease in exercise,
      whether the result of health (HR 0.56 vs no change in exercise, 95% CI 0.41-.78)
      or other reasons (HR 0.76 vs no change in exercise, 95% CI 0.63-.92), were
      associated with a lower likelihood of recovery from probable PTSD. Arriving early
      at the WTC (HR 1.38 vs later WTC arrival, 95% CI 1.12-1.70), an increasing number
      of aerodigestive symptoms (HR 1.45 per symptom, 95% CI 1.40-1.51), and reporting
      an increase in alcohol intake since September 11, 2001 (HR 3.43 vs no increase in
      alcohol intake, 95% CI 2.67-4.43) were associated with delayed onset of probable
      PTSD. CONCLUSIONS: Probable PTSD continues to be associated with early WTC
      arrival even 9 years after the terrorist attacks. Concurrent conditions and
      behaviors, such as respiratory symptoms, exercise, and alcohol use also play
      important roles in contributing to PTSD symptoms.

PMID- 21900418
TI  - How do plant viruses induce disease? Interactions and interference with host
      components.
AB  - Plant viruses are biotrophic pathogens that need living tissue for their
      multiplication and thus, in the infection-defence equilibrium, they do not
      normally cause plant death. In some instances virus infection may have no
      apparent pathological effect or may even provide a selective advantage to the
      host, but in many cases it causes the symptomatic phenotypes of disease. These
      pathological phenotypes are the result of interference and/or competition for a
      substantial amount of host resources, which can disrupt host physiology to cause
      disease. This interference/competition affects a number of genes, which seems to
      be greater the more severe the symptoms that they cause. Induced or repressed
      genes belong to a broad range of cellular processes, such as hormonal regulation,
      cell cycle control and endogenous transport of macromolecules, among others. In
      addition, recent evidence indicates the existence of interplay between plant
      development and antiviral defence processes, and that interference among the
      common points of their signalling pathways can trigger pathological
      manifestations. This review provides an update on the latest advances in
      understanding how viruses affect substantial cellular processes, and how plant
      antiviral defences contribute to pathological phenotypes.

PMID- 21900420
TI  - Human papillomavirus type-specific risk of cervical cancer in a population with
      high human immunodeficiency virus prevalence: case-control study.
AB  - There are limited data on human papillomavirus (HPV) type-specific cervical
      cancer risk among human immunodeficiency virus (HIV)-positive women. Previous
      studies have suggested that HPV 16 would be relatively less important as a
      causative agent among HIV-positive compared with HIV-negative women. This study
      investigates HPV type-specific cervical cancer risk in a population in which HIV
      is endemic. At the Central Hospital, Maputo, Mozambique, 221 cervical cancer
      cases and 203 hospital-based controls were consecutively enrolled. HPV typing
      from cervical samples, HIV testing and recording of socio-demographic factors
      were performed. Logistic regression modelling was used to assess HPV type
      specific risk and effect modification between HIV and HPV infection. Infection
      with HPV 16, 18 and 'high-risk non-HPV 16/18 types' (HPV 31, 33, 35, 39, 45, 51,
      52, 56, 58 and 59) was associated with cervical cancer in both crude and adjusted
      analyses. HPV 16 and 18 were the most common types detected in cancer biopsies
      among both HIV-negative and HIV-positive women. There was no significant evidence
      of effect modification between any HPV type and HIV infection, and there were no
      significant differences in the HPV type-specific prevalence when cervical cancers
      among HIV-positive and HIV-negative women were compared. Within the limitations
      of the study, the relative importance of different HPV types in cervical
      carcinogenesis appears not to be modified greatly by HIV infection, suggesting
      that HPV vaccines might not need to be type-specifically modified to be suitable
      for populations where HIV is endemic.

PMID- 21900419
TI  - Factors associated with the seroprevalence of 26 cutaneous and two genital human
      papillomavirus types in organ transplant patients.
AB  - Viral skin infections are commonly present in organ transplant recipients (OTR).
      In this study, we aimed to identify factors associated with human papillomavirus
      (HPV) infections in OTR. Patients with solid-organ transplants were recruited
      from the outpatient nephrology and dermatology clinics in five European
      countries. Only patients with no current or past skin cancer were included in
      this analysis. Serum samples were analysed for antibodies to the L1 proteins of
      26 cutaneous and two genital HPV types from five phylogenetic genera (alpha,
      beta, gamma, MU and nu). The most consistent association was found between
      recreational sun exposure and the seroprevalence of all tested genera, except
      alpha. The antibody presence of any beta type was higher among people who had
      been transplanted at least 23 years prior to participation than in those who had
      been transplanted for less than 7 years. The prevalence of two gamma-HPV types
      (60 and 65) and three beta-HPV types (15, 38 and 49) was associated with time
      since transplantation. The presence of a high number of warts was associated with
      the presence of any MU-PV or nu-PV types, and having greater than 50 keratotic
      skin lesions was almost significantly associated with the presence of antibodies
      to two or more gamma-PV. Discrepancies in the results of the present study, as
      well as in previous reports, may depend on different methodologies and on
      geographical variations. Our results also indicate that further research with
      more standardized methods is needed to clarify the role of cutaneous HPV in OTR.

PMID- 21900421
TI  - Structural modelling and mutagenesis of human cytomegalovirus alkaline nuclease
      UL98.
AB  - Human cytomegalovirus encodes an alkaline nuclease, UL98, that is highly
      conserved among herpesviruses and has both endonuclease (endo) and exonuclease
      (exo) activities. This protein is thought to be important for viral replication
      and therefore represents a potential target for antiviral development; however,
      little is known about its structure or role in viral replication. Comparative
      structural modelling was used to build a model of UL98 based on the known
      structure of shutoff and exonuclease protein from Kaposi's sarcoma-associated
      herpesvirus. The model predicts that UL98 residues D254, E278 and K280 represent
      the critical aspartic acid, glutamic acid and lysine active-site residues,
      respectively, while R164 and S252 correspond to residues proposed to bind the 5'
      phosphate of the DNA substrate. UL98 with an amino-terminal hexahistidine tag was
      expressed in Escherichia coli, purified by affinity chromatography and confirmed
      to have exo and endo activities. Amino acid substitutions D254A, E278A, K280A and
      S252A virtually eliminated exo and endo activities, whereas R164A retained full
      endo activity but only 10 % of the exo activity compared with the wild-type
      enzyme. A mutant virus lacking UL98 was viable but severely attenuated for
      replication, while one expressing UL98(R164A) replicated normally. These results
      confirm the utility of the model in representing the active-site region of UL98
      and suggest a mechanism for the differentiation of endonuclease and exonuclease
      activities. These findings could facilitate the exploration of the roles of
      alkaline nucleases in herpesvirus replication and the rational design of
      inhibitors that target their enzymic activities.

PMID- 21900422
TI  - Generation and characterization of a recombinant Rift Valley fever virus
      expressing a V5 epitope-tagged RNA-dependent RNA polymerase.
AB  - The viral RNA-dependent RNA polymerase (RdRp; L protein) of Rift Valley fever
      virus (RVFV; family Bunyaviridae) is a 238 kDa protein that is crucial for the
      life cycle of the virus, as it catalyses both transcription of viral mRNAs and
      replication of the tripartite genome. Despite its importance, little is known
      about the intracellular distribution of the polymerase or its other roles during
      infection, primarily because of lack of specific antibodies that recognize L
      protein. To begin to address these questions we investigated whether the RVFV
      (MP12 strain) polymerase could tolerate insertion of the V5 epitope, as has been
      previously demonstrated for the Bunyamwera virus L protein. Insertion of the 14
      aa epitope into the polymerase sequence at aa 1852 resulted in a polymerase that
      retained functionality in a minigenome assay, and we were able to rescue
      recombinant viruses that expressed the modified L protein by reverse genetics.
      The L protein could be detected in infected cells by Western blotting with anti
      V5 antibodies. Examination of recombinant virus-infected cells by
      immunofluorescence revealed a punctate perinuclear or cytoplasmic distribution of
      the polymerase that co-localized with the nucleocapsid protein. The generation of
      RVFV expressing a tagged RdRp will allow detailed examination of the role of the
      viral polymerase in the virus life cycle.

PMID- 21900423
TI  - Analysis of the human immunodeficiency virus type 1 M group Vpu domains involved
      in antagonizing tetherin.
AB  - Zoonosis of chimpanzee simian immunodeficiency virus cpz to humans has given rise
      to both pandemic (M) and non-pandemic (O, N and P) groups of human
      immunodeficiency virus type-1 (HIV). These lentiviruses encode accessory
      proteins, including Vpu, which has been shown to reduce CD4 levels on the cell
      surface, as well as increase virion release from the cell by antagonizing
      tetherin (CD317, BST2). Here, we confirm that O group Vpus (Ca9 and BCF06) are
      unable to counteract tetherin or downregulate the protein from the cell surface,
      although they are still able to reduce cell-surface CD4 levels. We hypothesize
      that this inability to antagonize tetherin may have contributed to O group
      viruses failing to achieve pandemic levels of human-to-human transmission.
      Characterization of chimeric O/M group Vpus and Vpu mutants demonstrate that the
      Vpu-tetherin interaction is complex, involving several domains. We identify
      specific residues within the transmembrane proximal region that, along with the
      transmembrane domain, are crucial for tetherin counteraction and enhanced virion
      release. We have also shown that the critical domains are responsible for the
      localization of M group Vpu to the trans-Golgi network, where it relocalizes
      tetherin to counteract its function. This work sheds light on the acquisition of
      anti-tetherin activity and the molecular details of pandemic HIV infection in
      humans.

PMID- 21900424
TI  - Genus-specific recruitment of filovirus ribonucleoprotein complexes into budding
      particles.
AB  - The filoviral matrix protein VP40 orchestrates virus morphogenesis and budding.
      To do this it interacts with both the glycoprotein (GP1,2) and the
      ribonucleoprotein (RNP) complex components; however, these interactions are still
      not well understood. Here we show that for efficient VP40-driven formation of
      transcription and replication-competent virus-like particles (trVLPs), which
      contain both an RNP complex and GP1,2, the RNP components and VP40, but not GP1,2
      and VP40, must be from the same genus. trVLP preparations contained both
      spherical and filamentous particles, but only the latter were able to infect
      target cells and to lead to genome replication and transcription. Interestingly,
      the genus specificity of the VP40-RNP interactions was specific to the formation
      of filamentous trVLPs, but not to spherical particles. These results not only
      further our understanding of VP40 interactions, but also suggest that special
      care is required when using trVLP or VLP systems to model virus morphogenesis.

PMID- 21900426
TI  - Journal of the American Board of Family Medicine Sixth Annual Practice-based
      Research Network theme issue--They just keep getting better and better.
AB  - We have quite a rich issue this month related to practice-based research networks
      (PBRNs)--reflections on where they have been, where they should go, how they
      should happen; lessons learned about recruiting physicians and patients and new
      research methods; and several clinical studies from existing PBRNs. We had an
      amazing number of manuscripts submitted this year for the PBRN issue; as a
      result, this is a powerful issue. Some are under revision for future issues of
      the Journal of the American Board of Family Medicine, just as we have some
      articles from PBRNs appearing in most issues. PBRNs have deepened the family
      medicine research tradition. The importance of primary care research to build the
      evidence base of our clinical practice, plus the useful work building the methods
      of primary care research, distinguishes the pioneers in PBRNs. PBRNs are Health
      Improvement Networks and national treasures to be nurtured.

PMID- 21900425
TI  - Flavivirus-induced antibody cross-reactivity.
AB  - Dengue viruses (DENV) cause countless human deaths each year, whilst West Nile
      virus (WNV) has re-emerged as an important human pathogen. There are currently no
      WNV or DENV vaccines licensed for human use, yet vaccines exist against other
      flaviviruses. To investigate flavivirus cross-reactivity, sera from a human
      cohort with a history of vaccination against tick-borne encephalitis virus
      (TBEV), Japanese encephalitis virus (JEV) and yellow fever virus (YFV) were
      tested for antibodies by plaque reduction neutralization test. Neutralization of
      louping ill virus (LIV) occurred, but no significant neutralization of Murray
      Valley encephalitis virus was observed. Sera from some individuals vaccinated
      against TBEV and JEV neutralized WNV, which was enhanced by YFV vaccination in
      some recipients. Similarly, some individuals neutralized DENV-2, but this was not
      significantly influenced by YFV vaccination. Antigenic cartography techniques
      were used to generate a geometric illustration of the neutralization titres of
      selected sera against WNV, TBEV, JEV, LIV, YFV and DENV-2. This demonstrated the
      individual variation in antibody responses. Most sera had detectable titres
      against LIV and some had titres against WNV and DENV-2. Generally, LIV titres
      were similar to titres against TBEV, confirming the close antigenic relationship
      between TBEV and LIV. JEV was also antigenically closer to TBEV than WNV, using
      these sera. The use of sera from individuals vaccinated against multiple
      pathogens is unique relative to previous applications of antigenic cartography
      techniques. It is evident from these data that notable differences exist between
      amino acid sequence identity and mapped antigenic relationships within the family
      Flaviviridae.

PMID- 21900427
TI  - Engagement of family physicians seven years into maintenance of certification.
AB  - Transitioning Family Physicians to continuous Maintenance of Certification (MOC)
      was intended to support the quality improvement movement nationally, but it also
      risked decreasing their engagement due to the increased requirements for
      retaining certification. However, after completing the transition of all family
      physicians into MOC in 2010, participation appears higher than ever.

PMID- 21900428
TI  - No longer simply a Practice-based Research Network (PBRN) health improvement
      networks.
AB  - While primary care Practice-based Research Networks are best known for their
      original, research purpose, evidence accumulating over the last several years is
      demonstrating broader values of these collaborations. Studies have demonstrated
      their role in quality improvement and practice change, in continuing professional
      education, in clinician retention in medically underserved areas, and in
      facilitating transition of primary care organization. A role in informing and
      facilitating health policy development is also suggested. Taking into account
      this more robust potential, we propose a new title, the Health Improvement
      Network, and a new vision for Practice-based Research Networks.

PMID- 21900429
TI  - The Agency for Healthcare Research and Quality (AHRQ) Practice-Based Research
      Network (PBRN) relationship: delivering on an opportunity, challenges, and future
      directions.
AB  - Practice-based research networks (PBRNs) often lack sufficient funding to develop
      the underlying infrastructure necessary to conduct high-quality, pragmatic,
      policy-relevant studies. One mechanism introduced by the Agency for Healthcare
      Research and Quality (AHRQ) that held the potential to address this issue was the
      PBRN Master Contract Program. The program allows the AHRQ to fund tightly focused
      "research activities" and to create a partnership through the PBRN contracts.
      Although PBRNs expected Master Contracts to strengthen them, several issues limit
      the utility of these contracts. The funding levels are lower than that provided
      from other sources for comparable work. Although some Task Order Officers are
      diligent, responsive, and supportive, too frequently their zeal for specific
      results and heavy handed approaches have led to significant "scope creep" and
      unrealistic expectations. Finally, a mechanism to allow PBRNs and network
      clinicians to influence the direction of the research questions has not been well
      developed. We see value in a new approach that supports the ability of the AHRQ
      to (1) garner support from other government agencies to engage PBRNs in studies
      relevant to policymakers and PBRNs; (2) capitalize on the collaborative nature of
      PBRNs by developing projects that support collaboration; (3) provide modest
      funding for infrastructure; (4) avoid the unnecessary and costly regulatory
      oversight from OMB; and (5) develop sustained "lines of research" on a scale,
      currently unavailable through the Master Contract, that can meaningfully
      contribute to the shaping of health policy.

PMID- 21900430
TI  - Re: The Agency for Healthcare Research and Quality (AHRQ) Practice-Based Research
      Network (PBRN) relationship: delivering on an opportunity, challenges, and future
      directions.

PMID- 21900431
TI  - A tribute to Dr. David Lanier.

PMID- 21900432
TI  - Reports of persistent change in the clinical encounter following research
      participation: a report from the Primary Care Multiethnic Network (PRIME Net).
AB  - PURPOSE: Following anecdotal reports of unexpected patient and/or clinician
      behavior change in the primary care encounter in a previous study, we conducted
      this study to learn more about the short- and long-term effects on clinician
      and/or patient behavior from participation in a practice-based research network
      (PBRN) study. METHODS: Clinicians in two PBRN studies of Acanthosis nigricans
      were surveyed and interviewed 3 to 6 months following one study and surveyed 3 to
      5 years following a second study. We gathered data on clinicians' reports of
      behavior change in the encounter, the persistence of those changes, and the
      likely causes of reported changes. RESULTS: Eighty-six percent of clinicians in
      the short-term and 79% in the long-term samples reported more frequent diagnostic
      efforts, and 68% and 54%, respectively, reported more frequent preventive
      counseling after participation in the studies. Interview data suggested that
      several factors contributed to this reported behavior change: increased clinician
      knowledge, availability of a feasible tool to support counseling, change in
      patient receptivity/motivation, and creation of a new context for counseling.
      CONCLUSIONS: Reports of behavior change in the primary care encounter associated
      with a PBRN study suggest that PBRNs may be effective vehicles for education,
      translation, and practice change in addition to their value in research.

PMID- 21900433
TI  - Factors influencing work interference in patients with chronic low back pain: a
      Residency Research Network of Texas (RRNeT) study.
AB  - INTRODUCTION: Chronic low back pain (CLBP) is a disabling and expensive condition
      commonly seen in family physicians' offices. A complete understanding of factors
      contributing to patients' return to work remains elusive. OBJECTIVE: To describe
      patients with CLBP seen in family physicians' offices and to explore factors
      interfering with return to work. SUBJECTS: Three hundred sixty outpatients with
      CLBP for more than 3 months. SETTING: Ten participating family physicians'
      offices of the Residency Research Network of Texas. PRIMARY OUTCOME: The effect
      of pain on work effect as measured by a Likert scale. RESULTS: Patients were
      typically female (72%), overweight or obese (mean body mass index, 33.4), had
      pain for many years (mean, 13.6 years), and screened positive for recent
      depressive symptoms (83%). The majority of patients took at least some opioid
      medication for their pain (59%). Multivariate linear regression analysis found
      that the largest single contributor to effect on work was the subjects' score on
      the SF-36 physical function scale (beta = -0.382). Other contributors included
      average daily pain (beta = 0.189), the frequency of flare-ups of pain (beta =
      0.108), the effect of the painful flare-ups (beta = 0.170), and current
      depressive symptoms (beta = 0.131) (adjusted R(2) for model = 0.535). Age, sex,
      race/ethnicity, total time the patient has had CLBP, other comorbidities
      (including a diagnosis of depression), disability status, use of opioids, history
      of intimate partner violence, social support, and procedures attempted were not
      predictive. DISCUSSION: Future studies attempting to demonstrate the
      effectiveness of interventions in CLBP should measure depressive symptoms and the
      magnitude and effect of painful flare-ups, not just the overall pain score. The
      majority of CLBP patients seen in these practices take opioids for their pain.
      Screening and treating for depression may be reasonable for some patients, though
      evidence of its effectiveness is lacking.

PMID- 21900434
TI  - Does patient assessment of the quality of the primary care they receive predict
      subsequent outcomes? An Oklahoma Physicians Resource/Research Network (OKPRN)
      study.
AB  - INTRODUCTION: We analyzed data from a cohort of 782 older patients assembled in
      1999 to 2000 to determine whether baseline patient assessments of the quality of
      the primary care services they had received, measured using the Components of
      Primary Care Index (CPCI), were associated with subsequent changes in health
      related quality of life (HRQoL) and/or survival. METHODS: Longitudinal growth
      curve models were used to analyze changes in Quality of Well-Being (QWB-SA)
      scores over an average (S.D.) of 2.07 (1.07) years. Cox proportional hazards
      models were used to identify variables associated with mortality over an average
      of 8.26 years (6460 person-years). To reduce confounding by severity of illness,
      subjects were stratified into disabled, nondisabled high utilizers of primary
      care, and nondisabled low utilizers. Within subgroups, we controlled for number
      of chronic illnesses and scores on the General Health subscale of the Medical
      Outcomes Study Short Form-36 (SF-36). We also controlled for baseline age, sex,
      marital status, income, body mass index, educational attainment, duration of the
      relationship with current primary care physician (PCP), and number of visits to
      the PCP in the year before enrollment. Analyses took into account clustering of
      patients within PCP. RESULTS: Neither total CPCI nor any CPCI subscale score was
      associated with QWB-SA change over time. Higher ratings of Coordination of Care
      were associated with reduced survival in the disabled and nondisabled high
      utilizer subgroups (P = .007). CONCLUSIONS: Assuming that effective primary care
      results in better HRQoL and longer survival and that the CPCI captures important
      primary care attributes, older patients' level of satisfaction with the quality
      of their primary care may not be a good surrogate measure of effectiveness.

PMID- 21900435
TI  - Management of skin and soft tissue infections in community practice before and
      after implementing a "best practice" approach: an Iowa Research Network (IRENE)
      intervention study.
AB  - CONTEXT: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)
      is a major pathogen among skin and soft tissue infections (SSTIs). Most CA-MRSA
      infections are managed initially on an outpatient basis. It is critical that
      primary care clinicians recognize and appropriately treat patients suspected of
      having such infections. OBJECTIVE: To identify and evaluate best methods and
      procedures for primary care clinicians to manage skin and soft tissue infections.
      DESIGN, SETTING, AND PATIENTS: Preintervention/postintervention study in eight
      Iowa Research Network offices conducted between October 2007 and August 2010. We
      reviewed medical records of 216 patients with SSTI before a set of interventions
      (preintervention) and 118 patients after the intervention (postintervention).
      INTERVENTIONS: Included a focus group meeting at each office, distribution of a
      modified Centers for Disease Control and Prevention (CDC) algorithm, "Outpatient
      Management of MRSA Skin and Soft Tissue Infections," education handouts, and an
      office policy for patients with skin infections. MAIN OUTCOME MEASURES:
      Proportion of subjects who were prescribed an antibiotic that would cover MRSA at
      the initial visit and proportion who were prescribed an antibiotic that would
      cover MRSA at any time. RESULTS: Three hundred sixty-eight forms (244
      preintervention and 124 postintervention) were returned; 216 (89%)
      preintervention forms and 118 (95%) postintervention forms were usable.
      Multivariable logistic regression models found statistically significant and
      independent factors associated with MRSA coverage at the initial visit included
      being in the postintervention rather than the preintervention group, having an
      abscess component compared with cellulitis alone, having a culture sent, being
      prescribed two or fewer antibiotics, and not being hospitalized. CONCLUSIONS: The
      CDC algorithm was feasible for offices to use. Following a discussion of SSTI
      management in the outpatient setting, use of MRSA coverage increased both
      initially and overall. Thus, involving clinicians in a discussion about
      guidelines rather than simply providing guidelines or a didactic session may be a
      useful way to change physician practices.

PMID- 21900436
TI  - Improving the management of skin and soft tissue infections in primary care: a
      report from State Networks of Colorado Ambulatory Practices and Partners (SNOCAP
      USA) and the Distributed Ambulatory Research in Therapeutics Network (DARTNet).
AB  - BACKGROUND: Purulent skin and soft tissue infections (SSTIs) requiring medical
      attention are often managed in primary care. The prevalence of SSTIs caused by
      community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) has been
      increasing rapidly, including in otherwise healthy individuals. The Centers for
      Disease Control and Prevention (CDC) issued guidelines to improve the management
      of SSTIs in primary care. PURPOSE: In primary care settings, to assess the
      prevalence of CA-MRSA using an electronic chart audit and then evaluate SSTI
      management strategies consistent with CDC guidelines. METHODS: A practical
      intervention that compared a historical cohort to an intervention cohort of
      patients seen for SSTI in 16 primary care practices in two health care systems.
      The intervention included a ready-made kit for I & D procedures, MRSA information
      for clinicians, a patient information handout, provider education, and patient
      follow-up. RESULTS: A total of 3112 SSTI cases (cellulitis or purulent) were
      observed during the preintervention period and 1406 cases during the
      intervention. For purulent infections in the intervention period (n = 148),
      univariate and multivariate analyses showed no significant improvement in the
      rate of I & D procedures or cultures obtained but showed increased use of
      antibiotics overall and agents that typically cover MRSA strains (OR, 2.183; 95%
      CI, 1.443 to 3.303 and 2.624; 95% CI, 1.500 to 4.604, respectively). For
      infections that were cellulitis with or without purulence (n = 1258), overall
      rates in the use of antibiotics and those that cover MRSA increased
      significantly, but secular trends could not be ruled out as an explanation for
      this increase. CONCLUSION: In SSTIs, this intervention resulted in increased use
      of antibiotics, including antibiotics that typically cover MRSA strains, but did
      not demonstrate increased rates of recommended drainage procedures. It is
      replicable and portable, and may improve antibiotic selection in other settings.

PMID- 21900437
TI  - Prevalence, severity, and treatment of community-acquired methicillin-resistant
      Staphylococcus aureus (CA-MRSA) skin and soft tissue infections in 10 medical
      clinics in Texas: a South Texas Ambulatory Research Network (STARNet) study.
AB  - OBJECTIVES: Quantify the prevalence, measure the severity, and describe treatment
      patterns in patients who present to medical clinics in Texas with community
      acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) skin and soft
      tissue infections (SSTI). METHODS: Ten primary care clinics participated in this
      prospective, community-based study. Clinicians consented patients and collected
      clinical information, pictures, and wound swabs; data were processed centrally.
      MRSASelectTM was used for identification. Susceptibilities were determined via
      Etest(r). RESULTS: Overall, 73 of 119 (61%) patients presenting with SSTIs
      meeting eligibility requirements had CA-MRSA. Among these, 49% were male, 79%
      were Hispanic, and 30% had diabetes. Half (56%) of the lesions were >= 5 cm in
      diameter. Most patients had abscesses (82%) and many reported pain scores of >= 7
      of 10 (67%). Many presented with erythema (85%) or drainage (56%). Most received
      incision and drainage plus an antibiotic (64%). Antibiotic monotherapy was
      frequently prescribed: trimethoprim-sulfamethoxazole (TMP-SMX) (78%), clindamycin
      (4%), doxycycline (2%), and mupirocin (2%). The rest received TMP-SMX in
      combination with other antibiotics. TMP-SMX was frequently administered as one
      double-strength tablet twice daily. Isolates were 93% susceptible to clindamycin
      and 100% susceptible to TMP-SMX, doxycycline, vancomycin, and linezolid.
      CONCLUSIONS: We report a predominance of CA-MRSA SSTIs, favorable antibiotic
      susceptibilities, and frequent use of TMP-SMX in primary care clinics.

PMID- 21900438
TI  - Chronic non-cancer pain: a siren for primary care--a report from the PRImary Care
      MultiEthnic Network (PRIME Net).
AB  - INTRODUCTION: Patients with chronic non-cancer pain (CNCP) are common and have a
      high degree of morbidity. Previous studies document clinician frustration and
      variability in CNCP management. We conducted this study to gather in-depth
      clinicians' views about factors that affect management of CNCP. METHODS: We
      conducted a survey in the Primary Care MultiEthnic Network, a consortium of PBRNs
      of primary care clinicians practicing in low-income, medically underserved
      communities, and in a network of private primary care offices. RESULTS: Of 792
      clinicians surveyed, 497 (63%) participated. Responses and accompanying narrative
      comments clustered around 5 themes: (1) barriers to and uncertainties in optimal
      management; (2) the complex biopsychosocial nature of CNCP; (3) seriousness of
      prescription opioid abuse; (4) effort and burden required to properly manage
      CNCP; and (5) clinician commitment to provide care for CNCP patients and benefits
      of expanded care model for CNCP. One-third reported a severe outcome (death or
      life-threatening event) in a CNCP patient for whom they had prescribed opioids.
      Roughly one-third do not initiate prescribing of opioids. CONCLUSIONS: Guidelines
      and increased continuing medical education alone are unlikely to be the solutions
      to the challenges of CNCP management. Increased evidence for recommendations and
      resources for more comprehensive care management are needed.

PMID- 21900439
TI  - The influence of research compensation options on Practice-based Research Network
      (PBRN) physician participation: a North Texas (NorTex) PBRN study.
AB  - OBJECTIVE: To study the effect of two compensation approaches, continuing medical
      education (CME) credits (5 hours) or monetary ($150), on the participation rate
      of a physician needs assessment study. METHODS: Physicians representing family
      medicine, internal medicine, pediatric, and geriatrics specialties, and
      practicing in ambulatory primary care clinics affiliated with the North Texas
      Primary Care (NorTex) PBRN clinics, were recruited to complete a survey relevant
      to their subspecialty and to conduct a self-audit/abstraction of five medical
      records. Physicians were recruited from four health care systems, and the
      recruiting methods varied by system. Study outcome was the rate of study
      completion by type of incentive. RESULTS: One hundred five of 211 (49.8%)
      physicians approached to participate gave consent and 84 (39.8%) completed the
      study. There was no difference in the number of physicians randomly assigned to
      monetary compared with CME compensation for giving consent to participate
      (adjusted odds ratio = 1.42, confidence interval = 0.69, 2.93). However,
      physicians in the monetary compensation group were more likely to complete the
      study after giving consent (adjusted odds ratio = 4.70, confidence interval =
      1.25, 17.58). This monetary effect was also significant from the perspective of
      all physicians approached initially (adjusted odds ratio = 2.78, confidence
      interval = 1.16, 6.67). DISCUSSION: This study suggests that future PBRN
      investigators should receive monetary compensation for the opportunity cost of
      adding research activities to their already busy practices. This compensation may
      be especially vital for PBRNs to complete more ambitious projects requiring a
      significant time commitment from the participating physicians.

PMID- 21900440
TI  - Using patient monetary incentives and electronically derived patient lists to
      recruit patients to a clinical trial.
AB  - PURPOSE: To report using electronic medical record (EMR) data to identify
      patients eligible for a clinical trial and the impact of providing an honorarium
      and deadline on accrual. METHODS: Six practices using a common EMR participated
      in a cluster-randomized trial testing a self-administered, web-based familial
      risk assessment tool. EMR-derived lists of eligible patients were made available
      for provider review. An honorarium and deadline for responding in the patient
      recruitment letter were implemented in the last half of the recruitment process.
      RESULTS: We identified 22,376 potentially eligible patients. Lists not returned
      by providers accounted for 9840 (44%) patients. We mailed invitations to 11,956
      patients; 2398 (20%) requested more information and a consent document, 1489
      (12.5%) consented to participate, and 1305 (11%) completed the baseline data
      collection. Patients receiving the additional $2 and a deadline compared with
      those receiving the personal invitation alone had significantly higher interest
      in participating (25% vs. 17%, P = .0001) but were less likely to complete
      baseline data collection (57% vs. 65% P = .01). Once consented, 85% completed the
      study with no significant difference by recruitment approach. CONCLUSIONS: Using
      EMR data reduces the burden to identify potentially eligible patients. However,
      some providers still did not review and return the lists. Adding a $2 incentive
      and deadline for responding did not improve the rate of eligible patients
      consenting and completing the study. Other patient recruitment methods to get
      better response by providers and population from primary care offices must be
      explored.

PMID- 21900441
TI  - A logic model framework for evaluation and planning in a primary care practice
      based research network (PBRN).
AB  - Evaluating effective growth and development of a practice-based research network
      (PBRN) can be challenging. The purpose of this article is to describe the
      development of a logic model and how the framework has been used for planning and
      evaluation in a primary care PBRN. An evaluation team was formed consisting of
      the PBRN directors, staff, and its board members. After the mission and the
      target audience were determined, facilitated meetings and discussions were held
      with stakeholders to identify the assumptions, inputs, activities, outputs,
      outcomes, and outcome indicators. The long-term outcomes outlined in the final
      logic model are 2-fold: (1) improved health outcomes of patients served by PBRN
      community clinicians and (2) community clinicians are recognized leaders of
      quality research projects. The logic model proved useful in identifying
      stakeholder interests and dissemination activities as an area that required more
      attention in the PBRN. The logic model approach is a useful planning tool and
      project management resource that increases the probability that the PBRN mission
      will be successfully implemented.

PMID- 21900442
TI  - A method for obtaining an unbiased sample of family medicine patients for
      research purposes.
AB  - INTRODUCTION: Obtaining a representative patient sample for research purposes can
      be challenging. Classic probability sampling can be trusted, but these approaches
      are not always feasible; yet alternatives may introduce bias. We summarize
      relevant literature, the need for new approaches, and illustrate a practical
      hybrid approach that could consistently produce representative patient samples.
      METHODS: Valid approaches shift sampling decisions from fallible interviewers to
      less fallible reproducible processes. In lieu of the interviewer's inclination to
      select particular patients, we used the day of the week, the appointment time,
      and the sequence of the patient's last name in the alphabet to select a sample
      for a consent process and a survey. ILLUSTRATIVE USE: Characteristics of the
      study sample (n = 225) were compared with the characteristics of the population
      (N = 1964) that had an office visit during the recruiting period. The data
      suggested that the study sample was highly representative of the population in
      this illustrative case. DISCUSSION: A hybrid sampling approach, in the context of
      a brief consent process, and a nonthreatening interview produced a representative
      study sample, but formal evaluation via simulation is needed to validate the
      hybrid approach. Convenience samples of consecutive patients should be avoided to
      minimize bias.

PMID- 21900443
TI  - Quasi-experimental designs in practice-based research settings: design and
      implementation considerations.
AB  - BACKGROUND: Although randomized controlled trials are often a gold standard for
      determining intervention effects, in the area of practice-based research (PBR),
      there are many situations in which individual randomization is not possible.
      Alternative approaches to evaluating interventions have received increased
      attention, particularly those that can retain elements of randomization such that
      they can be considered "controlled" trials. METHODS: Methodological design
      elements and practical implementation considerations for two quasi-experimental
      design approaches that have considerable promise in PBR settings--the stepped
      wedge design, and a variant of this design, a wait-list cross-over design, are
      presented along with a case study from a recent PBR intervention for patients
      with diabetes. RESULTS: PBR-relevant design features include: creation of a
      cohort over time that collects control data but allows all participants (clusters
      or patients) to receive the intervention; staggered introduction of clusters;
      multiple data collection points; and one-way cross-over into the intervention
      arm. Practical considerations include: randomization versus stratification,
      training run in phases; and extended time period for overall study completion.
      CONCLUSION: Several design features of practice based research studies can be
      adapted to local circumstances yet retain elements to improve methodological
      rigor. Studies that utilize these methods, such as the stepped-wedge design and
      the wait-list cross-over design, can increase the evidence base for controlled
      studies conducted within the complex environment of PBR.

PMID- 21900444
TI  - Developing a network of community health centers with a common electronic health
      record: description of the Safety Net West Practice-based Research Network (SNW
      PBRN).
AB  - In 2001, community health center (CHC) leaders in Oregon established an
      organization to facilitate the integration of health information technology,
      including a shared electronic health record (EHR), into safety net clinics. The
      Oregon Community Health Information Network (shortened to OCHIN as other states
      joined) became a CHC information technology hub, supporting a network-wide EHR
      with one master patient index, now linked across >40 safety net organizations
      serving >900,000 patients with nearly 800,000 distinct CHC visits. Recognizing
      the potential of OCHIN's multiclinic network and comprehensive EHR database for
      conducting safety net-based research, OCHIN leaders and local researchers formed
      the Safety Net West practice-based research network (PBRN). The Safety Net West
      "community- based laboratory," based at OCHIN, is positioned to become an
      important resource for many studies including: evaluation of the real-time impact
      of health care reform on uninsured populations; development of new models of
      primary care delivery; dissemination and translation of interventions from other
      EHR-based systems (e.g., Kaiser Permanente) into the community health setting;
      and analyses of factors influencing disparities in health and health care access.
      We describe the founding of Safety Net West, its infrastructure development,
      current projects, and the future goals of this community-based PBRN with a common
      EHR.

PMID- 21900445
TI  - A novel protocol for streamlined IRB review of Practice-based Research Network
      (PBRN) card studies.
AB  - PURPOSE: The "card study," in which clinicians record brief information about
      patient visits during usual clinical care, has long been a rapid method for
      conducting descriptive studies in practice-based research networks. Because an
      increasingly stringent regulatory environment has made conducting card studies
      difficult, we developed a streamlined method for obtaining card study
      institutional review board (IRB) approval. METHODS: We developed a protocol for a
      study of the card study method, allowing new card study proposals of specific
      research questions to be submitted as addenda to the approved Card Study
      Protocol. RESULTS: Seven card studies were proposed and approved under the Card
      Study Protocol during the first year after implementation, contrasted with one
      card study proposed in the previous year. New card study ideas submitted as
      addenda to an approved protocol appeared to increase IRB comfort with the card
      study as a minimal risk method while reducing the hurdles to developing new study
      ideas. CONCLUSIONS: A Card Study Protocol allowing new study questions to be
      submitted as addenda decreases time between idea generation and IRB approval.
      Shortened turn-around times may be useful for translating ideas into action while
      reducing regulatory burden.

PMID- 21900446
TI  - Recruiting Practice-based Research Network (PBRN) physicians to be research
      participants: lessons learned from the North Texas (NorTex) needs assessment
      study.
AB  - INTRODUCTION: The purpose of this study was to examine strategies for recruiting
      physician subjects in a practice-based research network continuing education
      research study, using different recruitment methods at four systems, or health
      plan arrangements. METHODS: The North Texas Primary Care Practice-based Research
      Network Needs Assessment Study consisted of a survey and five self-directed
      medical record abstractions. Physicians were recruited to be research subjects
      from four systems, using different recruitment strategies. chi(2) was used to
      determine differences in physicians consenting and completing the study between
      systems. Kruskal-Wallis was used to determine differences in time from first
      contact to consent and number of contacts required before consent between
      systems. RESULTS: One hundred five of 211 physicians (49.8%) consented to
      participate, of which 90 (85.7%) completed the survey. There was a significant
      difference by system in the number of physicians who consented (P = .04) and
      number of contacts required pre-consent (P < .001) but not in the number of
      physicians completing the study or time from first contact to consent.
      DISCUSSION/CONCLUSIONS: Success of recruiting physicians to be research subjects
      varied between systems using different recruitment methods. Lessons learned
      include using clinician champions to make initial contact, establishing a
      relationship with clinic personnel, distinguishing the research team from a
      pharmaceutical representative, establishing a preferred contact method, and
      collecting study materials on a set timeline.

PMID- 21900447
TI  - Re: The effects of patient-provider communication on 3-month recovery from acute
      low back pain.

PMID- 21900448
TI  - Re: Living on the edge.

PMID- 21900450
TI  - Defective nitric oxide production impairs angiotensin II-induced Na-K-ATPase
      regulation in spontaneously hypertensive rats.
AB  - Angiotensin (ANG) II via ANG II type 1 receptors (AT1R) activates renal sodium
      transporters including Na-K-ATPase and regulates sodium homeostasis and blood
      pressure. It is reported that at a high concentration, ANG II either inhibits or
      fails to stimulate Na-K-ATPase. However, the mechanisms for these phenomena are
      not clear. Here, we identified the signaling molecules involved in regulation of
      renal proximal tubular Na-K-ATPase at high ANG II concentrations. Proximal
      tubules from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats
      were incubated with low concentrations of ANG II (pM), which activated Na-K
      ATPase in both the groups; however, the stimulation was more robust in SHR. A
      high concentration of ANG II (MUM) failed to stimulate Na-K-ATPase in WKY rats.
      However, in SHR ANG II (MUM) continued to stimulate Na-K-ATPase, which was
      sensitive to the AT1R antagonist candesartan. In the presence of N(G)-nitro-l
      arginine methyl ester (l-NAME), a nitric oxide (NO) synthase (NOS) inhibitor, ANG
      II (MUM) caused stimulation of Na-K-ATPase in proximal tubules of WKY rats while
      having no further stimulatory effect in SHR. ANG II (MUM), via AT1R, increased
      proximal tubular NO levels in WKY rats but not in SHR. In SHR, NOS was uncoupled
      as incubation of proximal tubules with ANG II and l-arginine, a NOS substrate,
      caused superoxide generation only in SHR and not in WKY rats. The superoxide
      production in SHR was sensitive to l-NAME. There was exaggerated proximal tubular
      AT1R-G protein coupling and NAD(P)H oxidase activation in response to ANG II
      (MUM) in proximal tubules of SHR compared with WKY rats. In SHR, inhibition of
      NADPH oxidase restored NOS coupling and ANG II-induced NO accumulation. In
      conclusion, at a high concentration ANG II (MUM) activates renal NO signaling,
      which prevents stimulation of Na-K-ATPase in WKY rats. However, in SHR ANG II
      (MUM) overstimulates NADPH oxidase, which impairs the NO system and leads to
      continued Na-K-ATPase activation.

PMID- 21900451
TI  - WT1-interacting protein (Wtip) regulates podocyte phenotype by cell-cell and cell
      matrix contact reorganization.
AB  - Podocytes respond to environmental cues by remodeling their slit diaphragms and
      cell-matrix adhesive junctions. Wt1-interacting protein (Wtip), an Ajuba family
      LIM domain scaffold protein expressed in the podocyte, coordinates cell adhesion
      changes and transcriptional responses to regulate podocyte phenotypic plasticity.
      We evaluated effects of Wtip on podocyte cell-cell and cell-matrix contact
      organization using gain-of- and loss-of-function methods. Endogenous Wtip
      targeted to focal adhesions in adherent but isolated podocytes and then shifted
      to adherens junctions after cells made stable, homotypic contacts. Podocytes with
      Wtip knockdown (shWtip) adhered but failed to spread normally. Noncontacted
      shWtip podocytes did not assemble actin stress fibers, and their focal adhesions
      failed to mature. As shWtip podocytes established cell-cell contacts, stable
      adherens junctions failed to form and F-actin structures were disordered. In
      shWtip cells, cadherin and beta-catenin clustered in irregularly distributed
      spots that failed to laterally expand. Cell surface biotinylation showed
      diminished plasma membrane cadherin, beta-catenin, and alpha-catenin in shWtip
      podocytes, although protein expression was similar in shWtip and control cells.
      Since normal actin dynamics are required for organization of adherens junctions
      and focal adhesions, we determined whether Wtip regulates F-actin assembly.
      Undifferentiated podocytes did not elaborate F-actin stress fibers, but when
      induced to overexpress WTIP, formed abundant stress fibers, a process blocked by
      the RhoA inhibitor C3 toxin and a RhoA kinase inhibitor. WTIP directly interacted
      with Rho guanine nucleotide exchange factor (GEF) 12 (Arhgef12), a RhoA-specific
      GEF enriched in the glomerulus. In conclusion, stable assembly of podocyte
      adherens junctions and cell-matrix contacts requires Wtip, a process that may be
      mediated by spatiotemporal regulation of RhoA activity through appropriate
      targeting of Arhgef12.

PMID- 21900452
TI  - Hypoxia modulates the undifferentiated phenotype of human renal inner medullary
      CD133+ progenitors through Oct4/miR-145 balance.
AB  - Low-oxygen tension is an important component of the stem cell microenvironment.
      In rodents, renal resident stem cells have been described in the papilla, a
      relatively hypoxic region of the kidney. In the present study, we found that
      CD133(+) cells, previously described as renal progenitors in the human cortex,
      were enriched in the renal inner medulla and localized within the Henle's loop
      and thin limb segments. Once isolated, the CD133(+) cell population expressed
      renal embryonic and stem-related transcription factors and was able to
      differentiate into mature renal epithelial cells. When injected subcutaneously in
      immunodeficient mice within Matrigel, CD133(+) cells generated canalized
      structures positive for renal specific markers of different nephron segments.
      Oct4A levels and differentiation potential of papillary CD133(+) cells were
      higher than those of CD133(+) cells from cortical tubuli. Hypoxia was able to
      promote the undifferentiated phenotype of CD133(+) progenitors from papilla.
      Hypoxia stimulated clonogenicity, proliferation, vascular endothelial growth
      factor synthesis, and expression of CD133 that were in turn reduced by epithelial
      differentiation with parallel HIF-1alpha downregulation. In addition, hypoxia
      downregulated microRNA-145 and promoted the synthesis of Oct4A. Epithelial
      differentiation increased microRNA-145 and reduced Oct4 level, suggesting a
      balance between Oct4 and microRNA-145. MicroRNA-145 overexpression in CD133(+)
      cells induced downrelation of Oct4A at the protein level, inhibited cell
      proliferation, and stimulated terminal differentiation. This study underlines the
      role of the hypoxic microenvironment in controlling the proliferation and
      maintaining a progenitor phenotype and stem/progenitor properties of CD133(+)
      cells of the nephron. This mechanism may be at the basis of the maintenance of a
      CD133(+) population in the papillary region and may be involved in renal
      regeneration after injury.

PMID- 21900453
TI  - Hydration status affects urea transport across rat urothelia.
AB  - Although mammalian urinary tract epithelium (urothelium) is generally considered
      impermeable to water and solutes, recent data suggest that urine constituents may
      be reabsorbed during urinary tract transit and storage. To study water and solute
      transport across the urothelium in an in vivo rat model, we instilled urine
      (obtained during various rat hydration conditions) into isolated in situ rat
      bladders and, after a 1-h dwell, retrieved the urine and measured the differences
      in urine volume and concentration and total quantity of urine urea nitrogen and
      creatinine between instilled and retrieved urine in rat groups differing by
      hydration status. Although urine volume did not change >1.9% in any group,
      concentration (and quantity) of urine urea nitrogen in retrieved urine fell
      significantly (indicating reabsorption of urea across bladder urothelia), by a
      mean of 18% (489 mg/dl, from an instilled 2,658 mg/dl) in rats receiving ad
      libitum water and by a mean of 39% (2,544 mg/dl, from an instilled 6,204 mg/dl)
      in water-deprived rats, but did not change (an increase of 15 mg/dl, P = not
      significant, from an instilled 300 mg/dl) in a water-loaded rat group. Two
      separate factors affected urea nitrogen reabsorption rates, a urinary factor
      related to hydration status, likely the concentration of urea nitrogen in the
      instilled urine, and a bladder factor(s), also dependent on the animal's state of
      hydration. Urine creatinine was also absorbed during the bladder dwell, and
      hydration group effects on the concentration and quantity of creatinine
      reabsorbed were qualitatively similar to the hydration group effect on urea
      transport. These findings support the notion(s) that urinary constituents may
      undergo transport across urinary tract epithelia, that such transport may be
      physiologically regulated, and that urine is modified during transit and storage
      through the urinary tract.

PMID- 21900454
TI  - Hypothermic renal perfusion during aortic surgery reduces the presence of
      lipocalin-2 and preserves renal extraction of dimethylarginines in rats.
AB  - Cold perfusion through the renal arteries during renal ischemia has been
      suggested to diminish postoperative renal damage after juxtarenal aortic aneurysm
      repair. As the kidneys play a key role in dimethylarginine metabolism, which in
      turn is associated with renal hemodynamics, we hypothesized that the protective
      effect of cold perfusion is associated with a preserved renal extraction of
      dimethylarginines. Renal ischemia was induced in three groups of anesthetized
      Wistar rats (n = 7/group), which underwent suprarenal aortic clamping (45 min)
      with no perfusion (group 1), renal perfusion with 37 degrees C saline (group 2),
      or renal perfusion with 4 degrees C saline (group 3), respectively, followed by
      90 min of renal reperfusion in all groups. The sham group had no clamping. In
      group 3 (renal ischemia with cold perfusion), postoperative serum creatinine
      levels as well as the presence of luminal lipocalin-2 and its associated brush
      border damage were lower compared with groups 1 and 2 (P < 0.05). Also, renal
      extraction of asymmetrical (ADMA) and symmetrical (SDMA) dimethylarginine as well
      as the arginine/ADMA ratio, which defines the bioavailability of nitric oxide,
      remained intact in group 3 only (P < 0.04). The arginine/ADMA ratio correlated
      with cortical flow, lipocalin-2, and creatinine rises. Warm and cold renal
      perfusion (groups 2 and 3) during ischemia were similarly effective in lowering
      protein nitrosylation levels, renal leukocyte accumulation, neutrophil gelatinase
      associated lipocalin (NGAL) expression in distal tubules, and urine NGAL (P <
      0.05). These data support the use of cold renal perfusion during renal ischemia
      in situations where renal ischemia is inevitable, as it reduces tubular damage
      and preserves renal extraction of dimethylarginines. Renal perfusion with saline
      per se during renal ischemia is effective in diminishing renal leukocyte
      accumulation and oxidative stress.

PMID- 21900455
TI  - Decoy receptor 3 inhibits renal mononuclear leukocyte infiltration and apoptosis
      and prevents progression of IgA nephropathy in mice.
AB  - The progression of IgA nephropathy (IgAN), the most frequent type of primary
      glomerulonephritis, is associated with high levels of mononuclear leukocyte
      infiltration into the kidney. These cells consist mainly of T cells and
      macrophages. Our previous study showed that a decoy receptor 3 (DCR3) gene
      therapy can prevent the development of a mouse autoimmune glomerulonephritis
      model by its potent immune modulating effects (Ka SM, Sytwu HK, Chang DM, Hsieh
      SL, Tsai PY, Chen A. J Am Soc Nephrol 18: 2473-2485, 2007). Here, we tested the
      hypothesis that DCR3 might prevent the progression of IgAN, an immune complex
      mediated primary glomerulonephritis, by inhibiting T cell activation, renal T
      cell/macrophage infiltration, and protecting the kidney from apoptosis. We used a
      progressive IgAN (Prg-IgAN) model in B cell-deficient mice, because the mice are
      characterized by a dramatic proliferation of activated T cells systemically and
      progressive NF-kappaB activation in the kidney. We treated the animals with short
      term gene therapy with DCR3 plasmids by hydrodynamics-based gene delivery. When
      the mice were euthanized on day 21, we found that, compared with empty vector
      treated (disease control) Prg-IgAN mice, DCR3 gene therapy resulted in 1)
      systemic inhibition of T cell activation and proliferation; 2) lower serum levels
      of proinflammatory cytokines; 3) improved proteinuria, renal function, and renal
      pathology (inhibiting the development of marked glomerular proliferation,
      crescent formation, glomerulosclerosis, and interstitial inflammation); 5)
      suppression of T cell and macrophage infiltration into the periglomerular
      interstitium of the kidney; and 5) a reduction in apoptotic figures in the
      kidney. On the basis of these findings, DCR3 might be useful therapeutically in
      preventing the progression of IgAN.

PMID- 21900457
TI  - FXYD5 (dysadherin) regulates the paracellular permeability in cultured kidney
      collecting duct cells.
AB  - FXYD5 (dysadherin or RIC) is a member of the FXYD family of single-span
      transmembrane proteins associated with the Na(+)-K(+)-ATPase. Several studies
      have demonstrated enhanced expression of FXYD5 during metastasis and effects on
      cell adhesion and motility. The current study examines effects of FXYD5 on the
      paracellular permeability in the mouse kidney collecting duct cell line M1.
      Expressing FXYD5 in these cells leads to a large decrease in amiloride
      insensitive transepithelial electrical resistance as well as increased
      permeability to 4-kDa dextran. Impairment of cell-cell contact was also
      demonstrated by staining cells for the tight and adherence junction markers
      zonula occludens-1 and beta-catenin, respectively. This is further supported by
      large expansions of the interstitial spaces, visualized in electron microscope
      images. Expressing FXYD5 in M1 cells resulted in a decrease in N-glycosylation of
      beta1 Na(+)-K(+)-ATPase, while silencing it in H1299 cells had an opposite
      effect. This may provide a mechanism for the above effects, since normal
      glycosylation of beta1 plays an important role in cell-cell contact formation
      (Vagin O, Tokhtaeva E, Sachs G. J Biol Chem 281: 39573-39587, 2006).

PMID- 21900456
TI  - AT1 receptor-mediated augmentation of angiotensinogen, oxidative stress, and
      inflammation in ANG II-salt hypertension.
AB  - Augmentation of intrarenal angiotensinogen (AGT) synthesis, secretion, and
      excretion is associated with the development of hypertension, renal oxidative
      stress, and tissue injury during ANG II-dependent hypertension. High salt (HS)
      exacerbates hypertension and kidney injury, but the mechanisms remain unclear. In
      this study, we determined the consequences of HS intake alone compared with
      chronic ANG II infusion and combined HS plus ANG II on the stimulation of urinary
      AGT (uAGT), renal oxidative stress, and renal injury markers. Sprague-Dawley rats
      were subjected to 1) a normal-salt diet [NS, n = 5]; 2) HS diet [8% NaCl, n = 5];
      3) ANG II infusion in NS rats [ANG II 80 ng/min, n = 5]; 4) ANG II infusion in HS
      rats [ANG II+HS, n = 5]; and 5) ANG II infusion in HS rats treated with ANG II
      type 1 receptor blocker (ARB) [ANG II+HS+ARB, n = 5] for 14 days. Rats fed a HS
      diet alone did not show changes in systolic blood pressure (SBP), proteinuria,
      cell proliferation, or uAGT excretion although they did exhibit mesangial
      expansion, collagen deposition, and had increased NADPH oxidase activity
      accompanied by increased peroxynitrite formation in the kidneys. Compared with
      ANG II rats, the combination of ANG II infusion and a HS diet led to exacerbation
      in SBP (175 +/- 10 vs. 221 +/- 8 mmHg; P < 0.05), proteinuria (46 +/- 7 vs. 127
      +/- 7 mg/day; P < 0.05), and uAGT (1,109 +/- 70 vs.. 7,200 +/- 614 ng/day; P <
      0.05) associated with greater collagen deposition, mesangial expansion,
      interstitial cell proliferation, and macrophage infiltration. In both ANG II
      groups, the O(2)(-) levels were increased due to increased NADPH oxidase activity
      without concomitant increases in peroxynitrite formation. The responses in ANG II
      rats were prevented or ameliorated by ARB treatment. The results indicate that HS
      independently stimulates ROS formation, which may synergize with the effect of
      ANG II to limit peroxynitrite formation, leading to exacerbation of uAGT and
      greater injury during ANG II salt hypertension.

PMID- 21900459
TI  - A plea for vitamin D.

PMID- 21900460
TI  - The shortest way to reach nutritional goals is to adopt Mediterranean food
      choices: evidence from computer-generated personalized diets.
AB  - BACKGROUND: Dietary guidelines can be derived from dietary patterns known to be
      healthy such as the traditional Mediterranean diet. They can also be deduced by
      translating a set of nutrient recommendations into food combinations. However,
      the latter may vary depending on the decisions made by different expert
      committees. OBJECTIVE: The objective was to compare the effect of removing or
      adding selected nutrient recommendations on the dietary changes needed to fulfill
      a whole set of nutrient recommendations. DESIGN: For each adult participating in
      the French INCA dietary survey (Enquete Individuelle et Nationale sur les
      Consommations Alimentaires) (n = 1171), a nutritionally adequate diet was modeled
      that simultaneously met a whole set of nutrient goals (proteins, fiber, essential
      fatty acids, 10 vitamins, 9 minerals, sodium, saturated fatty acids, free sugars)
      while deviating the least from the observed diet in terms of food content. Eight
      sets of models were developed according to the inclusion or not of constraints on
      total fats, total carbohydrates, total MUFAs, and cholesterol. RESULTS: Compared
      with the observed intakes, fulfilling the whole set of nutrient constraints
      systematically decreased total fats and increased total carbohydrates, even in
      the absence of specific constraints on those macronutrients. For whichever model
      used, a strong consistency was observed in the dietary changes needed to fulfill
      the constraints, and the greatest increases were seen for unsalted nuts,
      unrefined grains, legumes, fruit, fish and shellfish, and vegetables. CONCLUSION:
      Whether recommendations on total fats, MUFAs, or total carbohydrates are included
      or not in the definition of overall nutrient adequacy, foods typical of the
      Mediterranean diet are needed to reach overall nutrient adequacy.

PMID- 21900458
TI  - Molecular regulation of NKCC2 in the thick ascending limb.
AB  - The kidney plays an essential role in blood pressure regulation by controlling
      short-term and long-term NaCl and water balance. The thick ascending limb of the
      loop of Henle (TAL) reabsorbs 25-30% of the NaCl filtered by the glomeruli in a
      process mediated by the apical Na(+)-K(+)-2Cl(-) cotransporter NKCC2, which
      allows Na(+) and Cl(-) entry from the tubule lumen into TAL cells. In humans,
      mutations in the gene coding for NKCC2 result in decreased or absent activity
      characterized by severe salt and volume loss and decreased blood pressure
      (Bartter syndrome type 1). Opposite to Bartter's syndrome, enhanced NaCl
      absorption by the TAL is associated with human hypertension and animal models of
      salt-sensitive hypertension. TAL NaCl reabsorption is subject to exquisite
      control by hormones like vasopressin, parathyroid, glucagon, and adrenergic
      agonists (epinephrine and norepinephrine) that stimulate NaCl reabsorption.
      Atrial natriuretic peptides or autacoids like nitric oxide and prostaglandins
      inhibit NaCl reabsorption, promoting salt excretion. In general, the mechanism by
      which hormones control NaCl reabsorption is mediated directly or indirectly by
      altering the activity of NKCC2 in the TAL. Despite the importance of NKCC2 in
      renal physiology, the molecular mechanisms by which hormones, autacoids, physical
      factors, and intracellular ions regulate NKCC2 activity are largely unknown.
      During the last 5 years, it has become apparent that at least three molecular
      mechanisms determine NKCC2 activity. As such, membrane trafficking,
      phosphorylation, and protein-protein interactions have recently been described in
      TALs and heterologous expression systems as mechanisms that modulate NKCC2
      activity. The focus of this review is to summarize recent data regarding NKCC2
      regulation and discuss their potential implications in physiological control of
      TAL function, renal physiology, and blood pressure regulation.

PMID- 21900461
TI  - Vitamin B-12 and homocysteine status in a folate-replete population: results from
      the Canadian Health Measures Survey.
AB  - BACKGROUND: Vitamin B-12 is an important cofactor required for nucleotide and
      amino acid metabolism. Vitamin B-12 deficiency causes anemia and neurologic
      abnormalities-a cause for concern for the elderly, who are at increased risk of
      vitamin B-12 malabsorption. Vitamin B-12 deficiency is also associated with an
      increased risk of neural tube defects and hyperhomocysteinemia. The metabolism of
      vitamin B-12 and folate is interdependent, which makes it of public health
      interest to monitor biomarkers of vitamin B-12, folate, and homocysteine in a
      folic acid-fortified population. OBJECTIVE: The objective was to determine the
      vitamin B-12, folate, and homocysteine status of the Canadian population in the
      period after folic acid fortification was initiated. DESIGN: Blood was collected
      from a nationally representative sample of ~5600 participants aged 6-79 y in the
      Canadian Health Measures Survey during 2007-2009 and was analyzed for serum
      vitamin B-12, red blood cell folate, and plasma total homocysteine (tHcy).
      RESULTS: A total of 4.6% of Canadians were vitamin B-12 deficient (<148 pmol/L).
      Folate deficiency (<320 nmol/L) was essentially nonexistent. Obese individuals
      were less likely to be vitamin B-12 adequate than were individuals with a normal
      BMI. A total of 94.9% of Canadians had a normal tHcy status (<=13 MUmol/L), and
      individuals with normal tHcy were more likely to be vitamin B-12 adequate and to
      have high folate status (>1090 nmol/L). CONCLUSIONS: Approximately 5% of
      Canadians are vitamin B-12 deficient. One percent of adult Canadians have
      metabolic vitamin B-12 deficiency, as evidenced by combined vitamin B-12
      deficiency and high tHcy status. In a folate-replete population, vitamin B-12 is
      a major determinant of tHcy.

PMID- 21900462
TI  - Folate consumption and cancer risk: a confirmation and some reassurance, but
      we're not out of the woods quite yet.

PMID- 21900463
TI  - Deciphering a methylome: what can we read into patterns of DNA methylation?
AB  - The methylation of cytosines within cytosine-guanine (CG) dinucleotides is an
      epigenetic mark that can modify gene transcription. With the advent of high
      throughput sequencing, it is possible to map methylomes, i.e. detect methylated
      CGs on a genome-wide scale. The methylomes sequenced to date reveal a divergence
      in prevalence and targeting of CG methylation between taxa, despite the
      conservation of the DNA methyltransferase enzymes that cause DNA methylation.
      Therefore, interspecific methylation usage is predicted to diverge. In various
      taxa, this tenet gains support from patterns of CG depletion that can be traced
      in DNA before methylomes are explicitly mapped. Depletion of CGs in methylated
      genomic regions is expected because methylated cytosines are subject to increased
      mutability caused by nucleotide deamination. However, the basis of diverging
      interspecific methylation usage is less clear. We use insights from the methylome
      of honeybees (Apis mellifera) to emphasize the possible importance of organismal
      life histories in explaining methylation usage and the accuracy of methylation
      prediction based on CG depletion. Interestingly, methylated genes in honeybees
      are more conserved across taxa than non-methylated genes despite the divergence
      in utilization of methylation and the increased mutability caused by deamination.

PMID- 21900464
TI  - No evidence for DPOAEs in the mechanical motion of the locust tympanum.
AB  - Distortion-product otoacoustic emissions (DPOAEs) are present in non-linear
      hearing organs, and for low-intensity sounds are a by-product of active
      processes. In vertebrate ears they are considered to be due to hair cell
      amplification of sound in the cochlea; however, certain animals lacking a cochlea
      and hair cells are also reported to be capable of DPOAEs. In the Insecta, DPOAEs
      have been recorded from the locust auditory organ. However, the site of
      generation of these DPOAEs and the physiological mechanisms causing their
      presence in the locust ear are not yet understood, despite there being a number
      of potential places in the tympanal organ that could be capable of generating
      DPOAEs. This study aimed to record locust tympanal membrane vibration using a
      laser Doppler vibrometer in order to identify a distinct place of DPOAE
      generation on the membrane. Two species of locust were investigated over a range
      of frequencies and levels of acoustic stimulus, mirroring earlier acoustic
      recording studies; however, the current experiments were carried out in an open
      acoustic system. The laser measurements did not find any evidence of mechanical
      motion on the tympanal membrane related to the expected DPOAE frequencies. The
      results of the current study therefore could not confirm the presence of DPOAEs
      in the locust ear through the mechanics of the tympanal membrane. Experiments
      were also carried out to test how membrane behaviour altered when the animals
      were in a state of hypoxia, as this was previously found to decrease DPOAE
      magnitude, suggesting a metabolic sensitivity. However, hypoxia did not have any
      significant effect on the membrane mechanics. The location of the mechanical
      generation of DPOAEs in the locust's ear, and therefore the basis for the related
      physiological mechanisms, thus remains unknown.

PMID- 21900465
TI  - Peripheral injury induces long-term sensitization of defensive responses to
      visual and tactile stimuli in the squid Loligo pealeii, Lesueur 1821.
AB  - Survivable injuries are a common yet costly experience. The ability to sense and
      respond to noxious stimuli is an almost universal trait, and prolonged behavioral
      alterations, including sensitization to touch and other stimuli, may function to
      ameliorate fitness costs associated with injury. Cephalopods can modify their
      behavior by learned association with noxious electric shock, but non-associative
      alterations of behavioral responses after tissue injury have not been studied.
      The aim of this study was to make the first systematic investigations in any
      cephalopod of behavioral responses and alterations elicited by explicit, minor
      injury. By testing responsiveness in the longfin squid, Loligo pealeii, to the
      approach and contact of an innocuous filament applied to different parts of the
      body both before and after injury to the distal third of one arm, we show that a
      cephalopod expresses behavioral alterations persisting for at least 2 days after
      injury. These alterations parallel forms of nociceptive plasticity in other
      animals, including general and site-specific sensitization to tactile stimuli. A
      novel finding is that hyper-responsiveness after injury extends to visual
      stimuli. Injured squid are more likely to employ crypsis than escape in response
      to an approaching visual stimulus shortly after injury, but initiate escape
      earlier and continue escape behaviors for longer when tested from 1 to 48 h after
      injury. Injury failed to elicit overt wound-directed behavior (e.g. grooming) or
      change hunting success. Our results show that long-lasting nociceptive
      sensitization occurs in cephalopods, and suggest that it may function to reduce
      predation risk after injury.

PMID- 21900466
TI  - Aerobic capacity in wild satin bowerbirds: repeatability and effects of age, sex
      and condition.
AB  - Individual variation in aerobic capacity has been extensively studied, especially
      with respect to condition, maturity or pathogen infection, and to gain insights
      into mechanistic foundations of performance. However, its relationship to mate
      competition is less well understood, particularly for animals in natural
      habitats. We examined aerobic capacity [maximum rate of O2 consumption (VO2,max)
      in forced exercise] in wild satin bowerbirds, an Australian passerine with a non
      resource based mating system and strong intermale sexual competition. We tested
      for repeatability of mass and VO2,max, differences among age and sex classes, and
      effects of several condition indices. In adult males, we examined interactions
      between aerobic performance and bower ownership (required for male mating
      success). There was significant repeatability of mass and VO2,max within and
      between years, but between-year repeatability was lower than within-year
      repeatability. VO2,max varied with an overall scaling to mass(0.791), but most
      variance in VO2,max was not explained by mass. Indicators of condition (tarsus
      and wing length asymmetry, the ratio of tarsus length to mass) were not
      correlated to VO2,max. Ectoparasite counts were weakly correlated to VO2,max
      across all age-sex classes but not within any class. Adult males, the cohort with
      the most intense levels of mating competition, had higher VO2,max than juvenile
      birds or adult females. However, there was no difference between the VO2,max of
      bower-owning males and that of males not known to hold bowers. Thus one major
      factor determining male reproductive success was not correlated to aerobic
      performance.

PMID- 21900467
TI  - Causes and consequences of stolon regression in a colonial hydroid.
AB  - A cnidarian colony can be idealized as a group of feeding polyps connected by
      tube-like stolons. Morphological variation ranges from runner-like forms with
      sparse polyp and stolon development to sheet-like forms with dense polyp and
      stolon development. These forms have typically been considered in a foraging
      context, consistent with a focus on rates of polyp development relative to stolon
      elongation. At the same time, rates of stolon regression can affect this
      morphological variation; several aspects of regression were investigated in this
      context. More sheet-like forms were produced by periodic peroxide treatment,
      which induced high rates of stolon regression. Caspase inhibitors altered the
      effects of regression induced by peroxide or vitamin C. These inhibitors
      generally diminished physical regression and the abundance of associated reactive
      oxygen species. Caspase inhibitors also altered cellular ultrastructure,
      resulting in features suggestive of necrosis rather than apoptosis. At the same
      time, caspase inhibitors had little effect on reactive nitrogen species that are
      also associated with regression. Although regression is most easily triggered by
      pharmacological perturbations related to reactive oxygen species (e.g. peroxide
      or vitamin C), a variety of environmental effects, particularly restricted
      environments and an interaction between feeding and temperature, can also induce
      regression. Stolon regression may thus be a factor contributing to natural
      variation between runners and sheets.

PMID- 21900468
TI  - Spectral and duration sensitivity to light-at-night in 'blind' and sighted rodent
      species.
AB  - Light-at-night (LAN) has become a defining feature of human and animal ecosystems
      and may possibly compromise human and animal physiology and health. Spectral and
      acclimation duration (AD) sensitivity were compared between social voles
      (Microtus socialis) and 'blind' mole rats (Spalax ehrenbergi) in four increasing
      ADs (0, 1, 7 and 21 days) to LAN (1*30 min, 293 MUW cm(-2)) of three different
      monochromatic lights [blue (479 nm), yellow (586 nm) and red (697 nm)]. Animals
      were sampled for urine and oxygen consumption (V(O(2))) promptly after each LAN
      AD. Urine samples were analyzed for production rate, urinary 6-sulfatoxymelatonin
      and urinary metabolites of adrenalin and cortisol. Overall, the blue light
      elicited the greatest effects on the biological markers of M. socialis, whereas
      similar effects were detected for S. ehrenbergi in response to red light. The
      increasing LAN-AD resulted in a dose-dependent decrement of all markers tested,
      except of stress hormones, which showed a direct positive correlation with LAN
      AD. Our results suggest that: (1) photoperiod is an important cue for entraining
      physiological functions in the 'blind' S. ehrenbergi, which is essentially
      characterized by red-shifted sensitivity compared with the blue-shifted
      sensitivity detected for the sighted counterpart species, and (2) there is a
      strong association between LAN of the appropriate wavelength and adrenal
      endocrine responses, suggesting that LAN is a potential environmental stressor.

PMID- 21900469
TI  - Scaling of resting and maximum hopping metabolic rate throughout the life cycle
      of the locust Locusta migratoria.
AB  - The hemimetabolous migratory locust Locusta migratoria progresses through five
      instars to the adult, increasing in size from 0.02 to 0.95 g, a 45-fold change.
      Hopping locomotion occurs at all life stages and is supported by aerobic
      metabolism and provision of oxygen through the tracheal system. This allometric
      study investigates the effect of body mass (Mb) on oxygen consumption rate (MO2,
      MUmol h(-1)) to establish resting metabolic rate (MRO2), maximum metabolic rate
      during hopping (MMO2) and maximum metabolic rate of the hopping muscles
      (MMO2,hop) in first instar, third instar, fifth instar and adult locusts. Oxygen
      consumption rates increased throughout development according to the allometric
      equations MRO2=30.1Mb(0.83+/-0.02), MMO2=155Mb(1.01+/-0.02),
      MMO2,hop=120Mb(1.07+/-0.02) and, if adults are excluded, MMO2,juv=136Mb(0.97+/
      0.02) and MMO2,juv,hop=103Mb(1.02+/-0.02). Increasing body mass by 20-45% with
      attached weights did not increase mass-specific MMO2 significantly at any life
      stage, although mean mass-specific hopping MO2 was slightly higher (ca. 8%) when
      juvenile data were pooled. The allometric exponents for all measures of metabolic
      rate are much greater than 0.75, and therefore do not support West, Brown and
      Enquist's optimised fractal network model, which predicts that metabolism scales
      with a 3/4-power exponent owing to limitations in the rate at which resources can
      be transported within the body.

PMID- 21900470
TI  - Symmorphosis and the insect respiratory system: allometric variation.
AB  - Taylor and Weibel's theory of symmorphosis predicts that structures of the
      respiratory system are matched to maximum functional requirements with minimal
      excess capacity. We tested this hypothesis in the respiratory system of the
      migratory locust, Locusta migratoria, by comparing the aerobic capacity of the
      jumping muscles with the morphology of the oxygen cascade in the hopping legs
      using an intraspecific allometric analysis of different body mass (M(b)) at
      selected juvenile life stages. The maximum oxygen consumption rate of the hopping
      muscle during jumping exercise scales as M(b)(1.02+/-0.02), which parallels the
      scaling of mitochondrial volume in the hopping muscle, M(b)(1.02+/-0.08), and the
      total surface area of inner mitochondrial membrane, M(b)(0.99+/-0.10). Likewise,
      at the oxygen supply end of the insect respiratory system, there is congruence
      between the aerobic capacity of the hopping muscle and the total volume of
      tracheoles in the hopping muscle, M(b)(0.99+/-0.16), the total inner surface area
      of the tracheoles, M(b)(0.99+/-0.16), and the anatomical radial diffusing
      capacity of the tracheoles, M(b)(0.99+/-0.18). Therefore, the principles of
      symmorphosis are upheld at each step of the oxygen cascade in the respiratory
      system of the migratory locust.

PMID- 21900472
TI  - Intra-retinal variation of opsin gene expression in the guppy (Poecilia
      reticulata).
AB  - Although behavioural experiments demonstrate that colouration influences mate
      choice in many species, a complete understanding of this form of signalling
      requires information about colour vision in the species under investigation. The
      guppy (Poecilia reticulata) has become a model species for the study of colour
      based sexual selection. To investigate the role of opsin gene duplication and
      divergence in the evolution of colour-based mate choice, we used in situ
      hybridization to determine where the guppy's nine cone opsins are expressed in
      the retina. Long wavelength-sensitive (LWS) opsins were more abundant in the
      dorsal retina than in the ventral retina. One of the middle wavelength-sensitive
      opsins (RH2-1) exhibited the opposite pattern, while the other middle wavelength
      sensitive opsin (RH2-2) and the short wavelength-sensitive opsins (SWS1, SWS2A
      and SWS2B) were expressed throughout the retina. We also found variation in LWS
      opsin expression among individuals. These observations suggest that regions of
      the guppy retina are specialized with respect to wavelength discrimination and/or
      sensitivity. Intra-retinal variability in opsin expression, which has been
      observed in several fish species, might be an adaptation to variation in the
      strength and spectral composition of light entering the eye from above and below.
      The discovery that opsin expression varies in the guppy retina may motivate new
      behavioural experiments designed to study its role in mate choice.

PMID- 21900473
TI  - Chronic hypoxia stimulates an enhanced response to immune challenge without
      evidence of an energetic tradeoff.
AB  - There is broad interest in whether there is a tradeoff between energy metabolism
      and immune function, and how stress affects immune function. Under hypoxic
      stress, maximal aerobic metabolism is limited, and other aspects of energy
      metabolism of animals may be altered as well. Although acute hypoxia appears to
      enhance certain immune responses, the effects of chronic hypoxia on immune
      function are largely unstudied. We tested: (1) whether chronic hypoxia affects
      immune function and (2) whether hypoxia affects the metabolic cost of immune
      function. First, flow cytometry was used to monitor the peripheral blood
      immunophenotype of mice over the course of 36 days of hypoxic exposure. Second,
      hypoxic and normoxic mice were subjected to an adaptive immune challenge via
      keyhole limpet hemocyanin (KLH) or to an innate immune challenge via
      lipopolysaccharide (LPS). The resting metabolic rates of mice in all immune
      challenge treatments were also measured. Although hypoxia had little effect on
      the peripheral blood immunophenotype, hypoxic mice challenged with KLH or LPS had
      enhanced immunological responses in the form of higher antibody titers or
      increased TNF-alpha production, respectively. Initially, mice exposed to hypoxia
      had lower metabolic rates, but this response was transitory and resting metabolic
      rates were normal by the end of the experiment. There was no effect of either
      immune challenge on resting metabolic rate, suggesting that mounting either the
      acute phase response or a humoral response is not as energetically expensive as
      previously thought. In addition, our results suggest that immune responses to
      chronic and acute hypoxia are concordant. Both forms of hypoxia appear to
      stimulate both innate and adaptive immune responses.

PMID- 21900471
TI  - Regulation of bat echolocation pulse acoustics by striatal dopamine.
AB  - The ability to control the bandwidth, amplitude and duration of echolocation
      pulses is a crucial aspect of echolocation performance but few details are known
      about the neural mechanisms underlying the control of these voice parameters in
      any mammal. The basal ganglia (BG) are a suite of forebrain nuclei centrally
      involved in sensory-motor control and are characterized by their dependence on
      dopamine. We hypothesized that pharmacological manipulation of brain dopamine
      levels could reveal how BG circuits might influence the acoustic structure of bat
      echolocation pulses. A single intraperitoneal injection of a low dose (5 mg kg(
      1)) of the neurotoxin 1-methyl-4-phenylpyridine (MPTP), which selectively targets
      dopamine-producing cells of the substantia nigra, produced a rapid degradation in
      pulse acoustic structure and eliminated the bat's ability to make compensatory
      changes in pulse amplitude in response to background noise, i.e. the Lombard
      response. However, high-performance liquid chromatography (HPLC) measurements of
      striatal dopamine concentrations revealed that the main effect of MPTP was a
      fourfold increase rather than the predicted decrease in striatal dopamine levels.
      After first using autoradiographic methods to confirm the presence and location
      of D(1)- and D(2)-type dopamine receptors in the bat striatum, systemic
      injections of receptor subtype-specific agonists showed that MPTP's effects on
      pulse acoustics were mimicked by a D(2)-type dopamine receptor agonist
      (Quinpirole) but not by a D(1)-type dopamine receptor agonist (SKF82958). The
      results suggest that BG circuits have the capacity to influence echolocation
      pulse acoustics, particularly via D(2)-type dopamine receptor-mediated pathways,
      and may therefore represent an important mechanism for vocal control in bats.

PMID- 21900474
TI  - Comparative gene expression profiles for highly similar aggressive phenotypes in
      male and female cichlid fishes (Julidochromis).
AB  - Julidochromis marlieri and Julidochromis transcriptus are two closely related
      Tanganyikan cichlids that have evolved different behavior and mating strategies
      since they diverged from their common ancestor. While J. transcriptus follows the
      ancestral pattern of male dominance, male-biased sexual size dimorphism and
      territoriality, the pattern is reversed in J. marlieri. In J. marlieri, females
      show all of these behavioral and morphological characteristics. This raises the
      question of whether female J. marlieri achieve the dominant phenotype by
      expressing the same genes as J. transcriptus males or whether novel brain gene
      expression patterns have evolved to produce a similar behavioral phenotype in the
      females of J. marlieri. This study used cDNA microarrays to investigate whether
      female J. marlieri and male J. transcriptus show conserved or divergent patterns
      of brain gene expression. Analysis of microarray data in both species showed
      certain gene expression patterns associated with sex role independent of gonadal
      sex and, to a lesser extent, gene expression patterns associated with sex
      independent of sex role. In general, these data suggest that while there has been
      substantial divergence in gene expression patterns between J. transcriptus and J.
      marlieri, we can detect a highly significant overlap for a core set of genes
      related to aggression in both species. These results suggest that the proximate
      mechanisms regulating aggressive behavior in J. transcriptus and J. marlieri may
      be shared.

PMID- 21900475
TI  - Pulmonary compliance and lung volume varies with ecomorphology in anuran
      amphibians: implications for ventilatory-assisted lymph flux.
AB  - Vertical movement of lymph from ventral regions to the dorsally located lymph
      hearts in anurans is accomplished by specialized skeletal muscles working in
      concert with lung ventilation. We hypothesize that more terrestrial species with
      greater lymph mobilization capacities and higher lymph flux rates will have
      larger lung volumes and higher pulmonary compliance than more semi-aquatic or
      aquatic species. We measured in situ mean and maximal compliance
      (Deltavolume/Deltapressure), distensibility (%Deltavolume/Deltapressure) and lung
      volume over a range of physiological pressures (1.0 to 4.0 cmH(2)O) for nine
      species of anurans representing three families (Bufonide, Ranidae and Pipidae)
      that span a range of body masses and habitats from terrestrial to aquatic. We
      further examined the relationship between these pulmonary variables and lymph
      flux for a semi-terrestrial bufonid (Rhinella marina), a semi-aquatic ranid
      (Lithobates catesbeianus) and an aquatic pipid (Xenopus laevis). Allometric
      scaling of pulmonary compliance and lung volume with body mass showed significant
      differences at the family level, with scaling exponents ranging from ~0.75 in
      Bufonidae to ~1.3 in Pipidae. Consistent with our hypothesis, the terrestrial
      Bufonidae species had significantly greater pulmonary compliance and greater lung
      volumes compared with semi-aquatic Ranidae and aquatic Pipidae species. Pulmonary
      distensibility ranged from ~20 to 35% cmH(2)O(-1) for the three families but did
      not correlate with ecomorphology. For the three species for which lymph flux data
      are available, R. marina had a significantly higher (P<0.001) maximal compliance
      (84.9+/-2.7 ml cmH(2)O(-1) kg(-1)) and lung volume (242.1+/-5.5 ml kg(-1))
      compared with L. catesbeianus (54.5+/-0.12 ml cmH(2)O(-1) kg(-1) and 139.3+/-0.5
      ml kg(-1)) and X. laevis (30.8+/-0.7 ml cmH(2)O(-1) kg(-1) and 61.3+/-2.5 ml kg(
      1)). Lymph flux rates were also highest for R. marina, lowest for X. laevis and
      intermediate in L. catesbeianus. Thus, there is a strong correlation between
      pulmonary compliance, lung volume and lymph flux rates, which suggests that lymph
      mobilization capacity may explain some of the variation in pulmonary compliance
      and lung volume in anurans.

PMID- 21900476
TI  - Roles of biogenic amines in regulating bioluminescence in the Australian glowworm
      Arachnocampa flava.
AB  - The glowworm Arachnocampa flava is a carnivorous fly larva (Diptera) that uses
      light to attract prey into its web. The light organ is derived from cells of the
      Malpighian tubules, representing a bioluminescence system that is unique to the
      genus. Bioluminescence is modulated through the night although light levels
      change quite slowly compared with the flashing of the better-known fireflies
      (Coleoptera). The existing model for the neural regulation of bioluminescence in
      Arachnocampa, based on use of anaesthetics and ligations, is that bioluminescence
      is actively repressed during the non-glowing phase and the repression is
      partially released during the bioluminescence phase. The effect of the
      anaesthetic, carbon dioxide, on the isolated light organ from the present study
      indicates that the repression is at least partially mediated at the light organ
      itself rather than less directly through the central nervous system. Blocking of
      neural signals from the central nervous system through ligation leads to
      uncontrolled release of bioluminescence but light is emitted at relatively low
      levels compared with under anaesthesia. Candidate biogenic amines were introduced
      by several methods: feeding prey items injected with test solution, injecting the
      whole larva, injecting a ligated section containing the light organ or bathing
      the isolated light organ in test solution. Using these methods, dopamine,
      serotonin and tyramine do not affect bioluminescence output. Exposure to elevated
      levels of octopamine via feeding, injection or bathing of the isolated light
      organ indicates that it is involved in the regulation of repression.
      Administration of the octopamine antagonists phentolamine or mianserin results in
      very high bioluminescence output levels, similar to the effect of anaesthetics,
      but only mianserin acts directly on the light organ.

PMID- 21900477
TI  - Social control of unreliable signals of strength in male but not female crayfish,
      Cherax destructor.
AB  - The maintenance of unreliable signals within animal populations remains a highly
      controversial subject in studies of animal communication. Crustaceans are an
      ideal group for studying unreliable signals of strength because their chela
      muscles are cryptically concealed beneath an exoskeleton, making it difficult for
      competitors to visually assess an opponent's strength. In this study, we examined
      the importance of social avenues for mediating the possible advantages gained by
      unreliable signals of strength in crustaceans. To do this, we investigated the
      factors that determine social dominance and the relative importance of signalling
      and fighting during aggressive encounters in male and female freshwater crayfish,
      Cherax destructor. Like other species of crayfish, we expected substantial
      variation in weapon force for a given weapon size, making the assessment of
      actual fighting ability of an opponent difficult from signalling alone. In
      addition, we expected fighting would be used to ensure that individuals that are
      weak for their signal (i.e. chela) size would not achieve higher than expected
      dominance. For both male and female C. destructor, we found large variation in
      the actual force of their chela for any given weapon size, indicating that it is
      difficult for competitors to accurately assess an opponent's force on signal size
      alone. For males, these unreliable signals of strength were controlled socially
      through increased levels of fighting and a decreased reliance on signalling, thus
      directly limiting the benefits accrued to individuals employing high-quality
      signals (large chelae) with only low resource holding potential. However, in
      contrast to our predictions, we found that females primarily relied on signalling
      to settle disputes, resulting in unreliable signals of strength being routinely
      used to establish dominance. The reliance by females on unreliable signals to
      determine dominance highlights our poor current understanding of the prevalence
      and distribution of dishonesty in animal communication.

PMID- 21900478
TI  - Long-term olfactory memories are stabilised via protein synthesis in Camponotus
      fellah ants.
AB  - Ants exhibit impressive olfactory learning abilities. Operant protocols in which
      ants freely choose between rewarded and non-rewarded odours have been used to
      characterise associative olfactory learning and memory. Yet, this approach
      precludes the use of invasive methods allowing the dissection of molecular bases
      of learning and memory. An open question is whether the memories formed upon
      olfactory learning that are retrievable several days after training are indeed
      based on de novo protein synthesis. Here, we addressed this question in the ant
      Camponotus fellah using a conditioning protocol in which individually harnessed
      ants learn an association between odour and reward. When the antennae of an ant
      are stimulated with sucrose solution, the insect extends its maxilla-labium to
      absorb the solution (maxilla-labium extension response). We differentially
      conditioned ants to discriminate between two long-chain hydrocarbons, one paired
      with sucrose and the other with quinine solution. Differential conditioning leads
      to the formation of a long-term memory retrievable at least 72 h after training.
      Long-term memory consolidation was impaired by the ingestion of cycloheximide, a
      protein synthesis blocker, prior to conditioning. Cycloheximide did not impair
      acquisition of either short-term memory (10 min) or early and late mid-term
      memories (1 or 12 h). These results show that, upon olfactory learning, ants form
      different memories with variable molecular bases. While short- and mid-term
      memories do not require protein synthesis, long-term memories are stabilised via
      protein synthesis. Our behavioural protocol opens interesting research avenues to
      explore the cellular and molecular bases of olfactory learning and memory in
      ants.

PMID- 21900479
TI  - Fatigue-related adaptations in muscle coordination during a cyclic exercise in
      humans.
AB  - Muscle fatigue is an exercise-induced reduction in the capability of a muscle to
      generate force. A possible strategy to counteract the effects of fatigue is to
      modify muscle coordination. We designed this study to quantify the effect of
      fatigue on muscle coordination during a cyclic exercise involving numerous
      muscles. Nine human subjects were tested during a constant-load rowing exercise
      (mean power output: 217.9+/-32.4 W) performed until task failure. The forces
      exerted at the handle and the foot-stretcher were measured continuously and were
      synchronized with surface electromyographic (EMG) signals measured in 23 muscles.
      In addition to a classical analysis of individual EMG data (EMG profile and EMG
      activity level), a non-negative matrix factorization algorithm was used to
      identify the muscle synergies at the start and the end of the test. Among the 23
      muscles tested, 16 showed no change in their mean activity level across the
      rowing cycle, five (biceps femoris, gluteus maximus, semitendinosus, trapezius
      medius and vastus medialis) showed a significant increase and two (gastrocnemius
      lateralis and longissimus) showed a significant decrease. We found no change in
      the number of synergies during the fatiguing test, i.e. three synergies accounted
      for more than 90% of variance accounted for at the start (92.4+/-1.5%) and at the
      end (91.0+/-1.8%) of the exercise. Very slight modifications at the level of
      individual EMG profiles, synergy activation coefficients and muscle synergy
      vectors were observed. These results suggest that fatigue during a cyclic task
      preferentially induces an adaptation in muscle activity level rather than changes
      in the modular organization of the muscle coordination.

PMID- 21900480
TI  - Forelimb kinematics and motor patterns of swimming loggerhead sea turtles
      (Caretta caretta): are motor patterns conserved in the evolution of new locomotor
      strategies?
AB  - Novel functions in animals may evolve through changes in morphology, muscle
      activity or a combination of both. The idea that new functions or behavior can
      arise solely through changes in structure, without concurrent changes in the
      patterns of muscle activity that control movement of those structures, has been
      formalized as the neuromotor conservation hypothesis. In vertebrate locomotor
      systems, evidence for neuromotor conservation is found across evolutionary
      transitions in the behavior of terrestrial species, and in evolutionary
      transitions from terrestrial species to flying species. However, evolutionary
      transitions in the locomotion of aquatic species have received little comparable
      study to determine whether changes in morphology and muscle function were
      coordinated through the evolution of new locomotor behavior. To evaluate the
      potential for neuromotor conservation in an ancient aquatic system, we quantified
      forelimb kinematics and muscle activity during swimming in the loggerhead sea
      turtle, Caretta caretta. Loggerhead forelimbs are hypertrophied into wing-like
      flippers that produce thrust via dorsoventral forelimb flapping. We compared
      kinematic and motor patterns from loggerheads with previous data from the red
      eared slider, Trachemys scripta, a generalized freshwater species exhibiting
      unspecialized forelimb morphology and anteroposterior rowing motions during
      swimming. For some forelimb muscles, comparisons between C. caretta and T.
      scripta support neuromotor conservation; for example, the coracobrachialis and
      the latissimus dorsi show similar activation patterns. However, other muscles
      (deltoideus, pectoralis and triceps) do not show neuromotor conservation; for
      example, the deltoideus changes dramatically from a limb protractor/elevator in
      sliders to a joint stabilizer in loggerheads. Thus, during the evolution of
      flapping in sea turtles, drastic restructuring of the forelimb was accompanied by
      both conservation and evolutionary novelty in limb motor patterns.

PMID- 21900481
TI  - Arabidopsis roots and shoots show distinct temporal adaptation patterns toward
      nitrogen starvation.
AB  - Nitrogen (N) is an essential macronutrient for plants. N levels in soil vary
      widely, and plants have developed strategies to cope with N deficiency. However,
      the regulation of these adaptive responses and the coordinating signals that
      underlie them are still poorly understood. The aim of this study was to
      characterize N starvation in adult Arabidopsis (Arabidopsis thaliana) plants in a
      spatiotemporal manner by an integrative, multilevel global approach analyzing
      growth, metabolites, enzyme activities, and transcript levels. We determined that
      the remobilization of N and carbon compounds to the growing roots occurred long
      before the internal N stores became depleted. A global metabolite analysis by gas
      chromatography-mass spectrometry revealed organ-specific differences in the
      metabolic adaptation to complete N starvation, for example, for several
      tricarboxylic acid cycle intermediates, but also for carbohydrates, secondary
      products, and phosphate. The activities of central N metabolism enzymes and the
      capacity for nitrate uptake adapted to N starvation by favoring N remobilization
      and by increasing the high-affinity nitrate uptake capacity after long-term
      starvation. Changes in the transcriptome confirmed earlier studies and added a
      new dimension by revealing specific spatiotemporal patterns and several unknown N
      starvation-regulated genes, including new predicted small RNA genes. No global
      correlation between metabolites, enzyme activities, and transcripts was evident.
      However, this multilevel spatiotemporal global study revealed numerous new
      patterns of adaptation mechanisms to N starvation. In the context of a
      sustainable agriculture, this work will give new insight for the production of
      crops with increased N use efficiency.

PMID- 21900482
TI  - A role for protein kinase casein kinase2 alpha-subunits in the Arabidopsis
      circadian clock.
AB  - Circadian rhythms are autoregulatory, endogenous rhythms with a period of
      approximately 24 h. A wide variety of physiological and molecular processes are
      regulated by the circadian clock in organisms ranging from bacteria to humans.
      Phosphorylation of clock proteins plays a critical role in generating proper
      circadian rhythms. Casein Kinase2 (CK2) is an evolutionarily conserved
      serine/threonine protein kinase composed of two catalytic alpha-subunits and two
      regulatory beta-subunits. Although most of the molecular components responsible
      for circadian function are not conserved between kingdoms, CK2 is a well
      conserved clock component modulating the stability and subcellular localization
      of essential clock proteins. Here, we examined the effects of a cka1a2a3 triple
      mutant on the Arabidopsis (Arabidopsis thaliana) circadian clock. Loss-of
      function mutations in three nuclear-localized CK2alpha subunits result in period
      lengthening of various circadian output rhythms and central clock gene
      expression, demonstrating that the cka1a2a3 triple mutant affects the pace of the
      circadian clock. Additionally, the cka1a2a3 triple mutant has reduced levels of
      CK2 kinase activity and CIRCADIAN CLOCK ASSOCIATED1 phosphorylation in vitro.
      Finally, we found that the photoperiodic flowering response, which is regulated
      by circadian rhythms, was reduced in the cka1a2a3 triple mutant and that the
      plants flowered later under long-day conditions. These data demonstrate that
      CK2alpha subunits are important components of the Arabidopsis circadian system
      and their effects on rhythms are in part due to their phosphorylation of
      CIRCADIAN CLOCK ASSOCIATED1.

PMID- 21900483
TI  - Brush and spray: a high-throughput systemic acquired resistance assay suitable
      for large-scale genetic screening.
AB  - Systemic acquired resistance (SAR) is a defense mechanism induced in the distal
      parts of plants after primary infection. It confers long-lasting protection
      against a broad spectrum of microbial pathogens. Lack of high-throughput assays
      has hampered the forward genetic analysis of SAR. Here, we report the development
      of an easy and efficient assay for SAR and its application in a forward genetic
      screen for SAR-deficient mutants in Arabidopsis (Arabidopsis thaliana). Using the
      new assay for SAR, we identified six flavin-dependent monooxygenase1, four AGD2
      like defense response protein1, three salicylic acid induction-deficient2, one
      phytoalexin deficient4, and one avrPphB-susceptible3 alleles as well as a gain-of
      function mutant of CALMODULIN-BINDING TRANSCRIPTION ACTIVATOR3 designated camta3
      3D. Like transgenic plants overexpressing CAMTA3, camta3-3D mutant plants exhibit
      compromised SAR and enhanced susceptibility to virulent pathogens, suggesting
      that CAMTA3 is a critical regulator of both basal resistance and SAR.

PMID- 21900484
TI  - Incidence of and risk factors for colistin-associated nephrotoxicity in a large
      academic health system.
AB  - BACKGROUND: Colistin, originally abandoned due to high rates of nephrotoxicity,
      has been recently reintroduced due to activity against carbapenem-resistant Gram
      negative organisms. Recent literature, largely obtained from outside the United
      States, suggests a lower rate of nephrotoxicity than historically reported.
      METHODS: A retrospective cohort of all patients who received colistin for >= 48
      hours at the Detroit Medical Center over a 5-year period was performed to
      determine the rate of colistin-associated nephrotoxicity as defined by the RIFLE
      criteria. RESULTS: Fifty-four (43%) patients in the cohort developed
      nephrotoxicity. Patients who experienced nephrotoxicity after colistin
      administration were in the Risk (13%), Injury (17%), or Failure (13%) categories
      per RIFLE criteria. Patients who developed nephrotoxicity received significantly
      higher mean doses than those who did not (5.48 mg/kg per day vs 3.95 mg/kg per
      day; P < .001), and the toxicity occurred in a dose-dependent fashion.
      Independent predictors for nephrotoxicity were a colistin dose of >= 5.0 mg/kg
      per day of ideal body weight (odds ratio [OR], 23.41; 95% confidence interval
      [CI], 5.3-103.55), receipt of concomitant rifampin (OR, 3.81; 95% CI, 1.42-10.2),
      and coadministration of >= 3 concomitant nephrotoxins (OR, 6.80; 95% CI, 1.42
      32.49). CONCLUSIONS: In this retrospective cohort, nephrotoxicity (as defined by
      RIFLE criteria) occurred among 43% of treated patients in a dose-dependent
      manner. Higher colistin doses, similar to those commonly used in the United
      States, led to a relatively high rate of nephrotoxicity. These data raise
      important questions regarding the safe use of colistin in the treatment of
      multidrug-resistant pathogens.

PMID- 21900485
TI  - The prescription of antimicrobials in Brazil.

PMID- 21900487
TI  - Prevalence of toscana and sicilian phlebovirus antibodies in classic Kaposi
      sarcoma case patients and control subjects in sicily.
AB  - To assess whether arthropod bites promote Kaposi sarcoma (KS), we determined the
      seroprevalence of Sicilian (SFSV) and Toscana (TOSV) phlebovirus antibodies in 30
      patients with classic KS and 100 controls in Sicily. Nine (6.9%) subjects, all
      controls, were positive for SFSV, whereas 41 (31.5%) were positive for TOSV.
      Seroprevalence with immunoglobulin (Ig) M or IgG against either virus was
      significantly higher in controls (43% vs 13.3% in case patients; P < .01).
      Adjusted for age, IgG seroprevalence was significantly lower in KS patients
      compared to controls (adjusted odds ratio, 0.22; 95% confidence interval, .07
      .72). Low phlebovirus seroprevalence in patients with KS may reflect incapacity
      to produce robust, persistent antibody responses, and suggests that arthropod
      bites do not promote KS.

PMID- 21900486
TI  - LPLUNC1 modulates innate immune responses to Vibrio cholerae.
AB  - BACKGROUND: Recent studies demonstrate that long palate, lung, and nasal
      epithelium clone 1 protein (LPLUNC1) is involved in immune responses to Vibrio
      cholerae, and that variations in the LPLUNC1 promoter influence susceptibility to
      severe cholera in humans. However, no functional role for LPLUNC1 has been
      identified. METHODS: We investigated the role of LPLUNC1 in immune responses to
      V. cholerae, assessing its affect on bacterial growth and killing and on innate
      inflammatory responses to bacterial outer membrane components, including purified
      lipopolysaccharide (LPS) and outer membrane vesicles. We performed immunostaining
      for LPLUNC1 in duodenal biopsies from cholera patients and uninfected controls.
      RESULTS: LPLUNC1 decreased proinflammatory innate immune responses to V. cholerae
      and Escherichia coli LPS. The effect of LPLUNC1 was dose-dependent and occurred
      in a TLR4-dependent manner. LPLUNC1 did not affect lipoprotein-mediated TLR2
      activation. Immunostaining demonstrated expression of LPLUNC1 in Paneth cells in
      cholera patients and controls. CONCLUSIONS: Our results demonstrate that LPLUNC1
      is expressed in Paneth cells and likely plays a role in modulating host
      inflammatory responses to V. cholerae infection. Attenuation of innate immune
      responses to LPS by LPLUNC1 may have implications for the maintenance of immune
      homeostasis in the intestine.

PMID- 21900488
TI  - Toll-like receptor 2 mediates fatal immunopathology in mice during treatment of
      secondary pneumococcal pneumonia following influenza.
AB  - Host inflammatory responses contribute to the significant immunopathology that
      occurs during treatment of secondary bacterial pneumonia following influenza. We
      undertook the present study to determine the mechanisms underlying disparate
      outcomes in a mouse model with beta-lactam and macrolide antibiotics. Lysis of
      superinfecting bacteria by ampicillin caused an extensive influx of neutrophils
      into the lungs resulting in a consolidative pneumonia, necrotic lung damage, and
      significant mortality. This was mediated through Toll-like receptor (TLR) 2 and
      was independent of TLR4 and the Streptococcus pneumoniae cytotoxin pneumolysin.
      Treatment with azithromycin prevented neutrophil accumulation and rescued mice
      from subsequent mortality. This effect was independent of the antibacterial
      activity of this macrolide since dual therapy with ampicillin and azithromycin
      against an azithromycin-resistant strain also was able to cure secondary
      pneumonia. These data suggest that strategies for eliminating bacteria without
      lysis coupled with immunomodulation of inflammation should be pursued clinically.

PMID- 21900489
TI  - The filament-forming protein Pil1 assembles linear eisosomes in fission yeast.
AB  - The cortical cytoskeleton mediates a range of cellular activities such as
      endocytosis, cell motility, and the maintenance of cell rigidity. Traditional
      polymers, including actin, microtubules, and septins, contribute to the cortical
      cytoskeleton, but additional filament systems may also exist. In yeast cells,
      cortical structures called eisosomes generate specialized domains termed MCCs to
      cluster specific proteins at sites of membrane invaginations. Here we show that
      the core eisosome protein Pil1 forms linear cortical filaments in fission yeast
      cells and that purified Pil1 assembles into filaments in vitro. In cells, Pil1
      cortical filaments are excluded from regions of cell growth and are independent
      of the actin and microtubule cytoskeletons. Pil1 filaments assemble slowly at the
      cell cortex and appear stable by time-lapse microscopy and fluorescence recovery
      after photobleaching. This stability does not require the cell wall, but Pil1 and
      the transmembrane protein Fhn1 colocalize and are interdependent for localization
      to cortical filaments. Increased Pil1 expression leads to cytoplasmic Pil1 rods
      that are stable and span the length of cylindrical fission yeast cells. We
      propose that Pil1 is a novel component of the yeast cytoskeleton, with
      implications for the role of filament assembly in the spatial organization of
      cells.

PMID- 21900490
TI  - The chromatin remodeler ISWI regulates the cellular response to hypoxia: role of
      FIH.
AB  - The hypoxia-inducible factor (HIF) is a master regulator of the cellular response
      to hypoxia. Its levels and activity are controlled by dioxygenases called prolyl
      hydroxylases and factor inhibiting HIF (FIH). To activate genes, HIF has to
      access sequences in DNA that are integrated in chromatin. It is known that the
      chromatin-remodeling complex switch/sucrose nonfermentable (SWI/SNF) is essential
      for HIF activity. However, no additional information exists about the role of
      other chromatin-remodeling enzymes in hypoxia. Here we describe the role of
      imitation switch (ISWI) in the cellular response to hypoxia. We find that unlike
      SWI/SNF, ISWI depletion enhances HIF activity without altering its levels.
      Furthermore, ISWI knockdown only alters a subset of HIF target genes.
      Mechanistically, we find that ISWI is required for full expression of FIH mRNA
      and protein levels by changing RNA polymerase II loading to the FIH promoter. Of
      interest, exogenous FIH can rescue the ISWI-mediated upregulation of CA9 but not
      BNIP3, suggesting that FIH-independent mechanisms are also involved. Of
      importance, ISWI depletion alters the cellular response to hypoxia by reducing
      autophagy and increasing apoptosis. These results demonstrate a novel role for
      ISWI as a survival factor during the cellular response to hypoxia.

PMID- 21900491
TI  - beta-Actin specifically controls cell growth, migration, and the G-actin pool.
AB  - Ubiquitously expressed beta-actin and gamma-actin isoforms play critical roles in
      most cellular processes; however, their unique contributions are not well
      understood. We generated whole-body beta-actin-knockout (Actb(-/-)) mice and
      demonstrated that beta-actin is required for early embryonic development.
      Lethality of Actb(-/-) embryos correlated with severe growth impairment and
      migration defects in beta-actin-knockout primary mouse embryonic fibroblasts
      (MEFs) that were not observed in gamma-actin-null MEFs. Migration defects were
      associated with reduced membrane protrusion dynamics and increased focal
      adhesions. We also identified migration defects upon conditional ablation of beta
      actin in highly motile T cells. Of great interest, ablation of beta-actin altered
      the ratio of globular actin (G-actin) to filamentous actin in MEFs, with
      corresponding changes in expression of genes that regulate the cell cycle and
      motility. These data support an essential role for beta-actin in regulating cell
      migration and gene expression through control of the cellular G-actin pool.

PMID- 21900492
TI  - STARD4 abundance regulates sterol transport and sensing.
AB  - Nonvesicular transport of cholesterol plays an essential role in the distribution
      and regulation of cholesterol within cells, but it has been difficult to identify
      the key intracellular cholesterol transporters. The steroidogenic acute
      regulatory-related lipid-transfer (START) family of proteins is involved in
      several pathways of nonvesicular trafficking of sterols. Among them, STARD4 has
      been shown to increase intracellular cholesteryl ester formation and is
      controlled at the transcriptional level by sterol levels in cells. We found that
      STARD4 is very efficient in transporting sterol between membranes in vitro.
      Cholesterol levels are increased in STARD4-silenced cells, while sterol transport
      to the endocytic recycling compartment (ERC) and to the endoplasmic reticulum
      (ER) are enhanced upon STARD4 overexpression. STARD4 silencing attenuates
      cholesterol-mediated regulation of SREBP-2 activation, while its overexpression
      amplifies sterol sensing by SCAP/SREBP-2. To analyze STARD4's mode of action, we
      compared sterol transport mediated by STARD4 with that of a simple sterol
      carrier, methyl-beta-cyclodextrin (MCD), when STARD4 and MCD were overexpressed
      or injected into cells. Interestingly, STARD4 and cytosolic MCD act similarly by
      increasing the rate of transfer of sterol to the ERC and to the ER. Our results
      suggest that cholesterol transport mediated by STARD4 is an important component
      of the cholesterol homeostasis regulatory machinery.

PMID- 21900493
TI  - Dual roles of Munc18-1 rely on distinct binding modes of the central cavity with
      Stx1A and SNARE complex.
AB  - Sec1/Munc18 proteins play a fundamental role in multiple steps of intracellular
      membrane trafficking. Dual functions have been attributed to Munc18-1: it can act
      as a chaperone when it interacts with monomeric syntaxin 1A, and it can activate
      soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs)
      for membrane fusion when it binds to SNARE complexes. Although both modes of
      binding involve the central cavity of Munc18-1, their precise molecular
      mechanisms of action are not fully understood. In this paper, we describe a novel
      Munc18-1 mutant in the central cavity that showed a reduced interaction with
      syntaxin 1A and impaired chaperone function, but still bound to assembled SNARE
      complexes and promoted liposome fusion and secretion in neuroendocrine cells.
      Soluble syntaxin 1A H3 domain partially blocks Munc18-1 activation of liposome
      fusion by occupying the Munc18-1 central cavity. Our findings lead us to propose
      a transition model between the two distinct binding modes by which Munc18 can
      control and assist in SNARE-complex assembly during neurotransmitter release.

PMID- 21900494
TI  - The tumor suppressor adenomatous polyposis coli controls the direction in which a
      cell extrudes from an epithelium.
AB  - Despite high rates of cell death, epithelia maintain intact barriers by squeezing
      dying cells out using a process termed cell extrusion. Cells can extrude apically
      into the lumen or basally into the tissue the epithelium encases, depending on
      whether actin and myosin contract at the cell base or apex, respectively. We
      previously found that microtubules in cells surrounding a dying cell target p115
      RhoGEF to the actin cortex to control where contraction occurs. However, what
      controls microtubule targeting to the cortex and whether the dying cell also
      controls the extrusion direction were unclear. Here we find that the tumor
      suppressor adenomatous polyposis coli (APC) controls microtubule targeting to the
      cell base to drive apical extrusion. Whereas wild-type cells preferentially
      extrude apically, cells lacking APC or expressing an oncogenic APC mutation
      extrude predominantly basally in cultured monolayers and zebrafish epidermis.
      Thus APC is essential for driving extrusion apically. Surprisingly, although APC
      controls microtubule reorientation and attachment to the actin cortex in cells
      surrounding the dying cell, it does so by controlling actin and microtubules
      within the dying cell. APC disruptions that are common in colon and breast cancer
      may promote basal extrusion of tumor cells, which could enable their exit and
      subsequent migration.

PMID- 21900495
TI  - Coupling of T161 and T14 phosphorylations protects cyclin B-CDK1 from premature
      activation.
AB  - Mitosis is triggered by the abrupt dephosphorylation of inhibitory Y15 and T14
      residues of cyclin B1-bound cyclin-dependent kinase (CDK)1 that is also
      phosphorylated at T161 in its activation loop. The sequence of events leading to
      the accumulation of fully phosphorylated cyclin B1-CDK1 complexes remains
      unclear. Two-dimensional gel electrophoresis allowed us to determine whether T14,
      Y15, and T161 phosphorylations occur on same CDK1 molecules and to characterize
      the physiological occurrence of their seven phosphorylation combinations.
      Intriguingly, in cyclin B1-CDK1, the activating T161 phosphorylation never
      occurred without the T14 phosphorylation. This strict association could not be
      uncoupled by a substantial reduction of T14 phosphorylation in response to Myt1
      knockdown, suggesting some causal relationship. However, T14 phosphorylation was
      not directly required for T161 phosphorylation, because Myt1 knockdown did
      uncouple these phosphorylations when leptomycin B prevented cyclin B1-CDK1
      complexes from accumulating in cytoplasm. The coupling mechanism therefore
      depended on unperturbed cyclin B1-CDK1 traffic. The unexpected observation that
      the activating phosphorylation of cyclin B1-CDK1 was tightly coupled to its T14
      phosphorylation, but not Y15 phosphorylation, suggests a mechanism that prevents
      premature activation by constitutively active CDK-activating kinase. This
      explained the opposite effects of reduced expression of Myt1 and Wee1, with only
      the latter inducing catastrophic mitoses.

PMID- 21900496
TI  - The SCAR/WAVE complex is necessary for proper regulation of traction stresses
      during amoeboid motility.
AB  - Cell migration requires a tightly regulated, spatiotemporal coordination of
      underlying biochemical pathways. Crucial to cell migration is SCAR/WAVE-mediated
      dendritic F-actin polymerization at the cell's leading edge. Our goal is to
      understand the role the SCAR/WAVE complex plays in the mechanics of amoeboid
      migration. To this aim, we measured and compared the traction stresses exerted by
      Dictyostelium cells lacking the SCAR/WAVE complex proteins PIR121 (pirA(-)) and
      SCAR (scrA(-)) with those of wild-type cells while they were migrating on flat,
      elastic substrates. We found that, compared to wild type, both mutant strains
      exert traction stresses of different strengths that correlate with their F-actin
      levels. In agreement with previous studies, we found that wild-type cells migrate
      by repeating a motility cycle in which the cell length and strain energy exerted
      by the cells on their substrate vary periodically. Our analysis also revealed
      that scrA(-) cells display an altered motility cycle with a longer period and a
      lower migration velocity, whereas pirA(-) cells migrate in a random manner
      without implementing a periodic cycle. We present detailed characterization of
      the traction-stress phenotypes of the various cell lines, providing new insights
      into the role of F-actin polymerization in regulating cell-substratum
      interactions and stresses required for motility.

PMID- 21900497
TI  - Coordinated regulation of sulfur and phospholipid metabolism reflects the
      importance of methylation in the growth of yeast.
AB  - A yeast strain lacking Met4p, the primary transcriptional regulator of the sulfur
      assimilation pathway, cannot synthesize methionine. This apparently simple
      auxotroph did not grow well in rich media containing excess methionine, forming
      small colonies on yeast extract/peptone/dextrose plates. Faster-growing large
      colonies were abundant when overnight cultures were plated, suggesting that
      spontaneous suppressors of the growth defect arise with high frequency. To
      identify the suppressor mutations, we used genome-wide single-nucleotide
      polymorphism and standard genetic analyses. The most common suppressors were loss
      of-function mutations in OPI1, encoding a transcriptional repressor of
      phospholipid metabolism. Using a new system that allows rapid and specific
      degradation of Met4p, we could study the dynamic expression of all genes
      following loss of Met4p. Experiments using this system with and without Opi1p
      showed that Met4 activates and Opi1p represses genes that maintain levels of S
      adenosylmethionine (SAM), the substrate for most methyltransferase reactions.
      Cells lacking Met4p grow normally when either SAM is added to the media or one of
      the SAM synthetase genes is overexpressed. SAM is used as a methyl donor in three
      Opi1p-regulated reactions to create the abundant membrane phospholipid,
      phosphatidylcholine. Our results show that rapidly growing cells require
      significant methylation, likely for the biosynthesis of phospholipids.

PMID- 21900499
TI  - Selective regulation of autophagy by the Iml1-Npr2-Npr3 complex in the absence of
      nitrogen starvation.
AB  - Autophagy is an evolutionarily conserved pathway for the degradation of
      intracellular contents. How autophagy is regulated, especially upon changes in
      metabolic and nutritional state, remains poorly understood. By using a
      prototrophic strain of Saccharomyces cerevisiae, we observed that, unexpectedly,
      autophagy is strongly induced simply upon switch from a rich medium to a minimal
      medium in the complete absence of nitrogen starvation. This novel form of
      autophagy was termed "non-nitrogen-starvation (NNS)-induced autophagy." A visual
      screen uncovered three regulators of autophagy-Iml1p, Npr2p, and Npr3p-which
      function in the same complex and are selectively required for NNS-induced
      autophagy. During NNS-induced autophagy, Iml1p localized to either
      preautophagosomal structures (PAS) or non-PAS punctate structures. This
      localization suggests that Iml1p or the Iml1p-Npr2p-Npr3p complex might regulate
      autophagosome formation. Ultrastructural analysis confirmed that autophagosome
      formation was strongly impaired in Deltaiml1, Deltanpr2, and Deltanpr3 cells
      during NNS-induced autophagy. Moreover, Iml1p contains a conserved domain that is
      required for NNS-induced autophagy as well as complex formation. Collectively,
      our findings have revealed the existence of additional mechanisms that regulate
      autophagy under previously unrecognized conditions, in response to relatively
      more subtle changes in metabolic and nutritional state.

PMID- 21900500
TI  - Novel function of keratins 5 and 14 in proliferation and differentiation of
      stratified epithelial cells.
AB  - Keratins are cytoplasmic intermediate filament proteins preferentially expressed
      by epithelial tissues in a site-specific and differentiation-dependent manner.
      The complex network of keratin filaments in stratified epithelia is tightly
      regulated during squamous cell differentiation. Keratin 14 (K14) is expressed in
      mitotically active basal layer cells, along with its partner keratin 5 (K5), and
      their expression is down-regulated as cells differentiate. Apart from the
      cytoprotective functions of K14, very little is known about K14 regulatory
      functions, since the K14 knockout mice show postnatal lethality. In this study,
      K14 expression was inhibited using RNA interference in cell lines derived from
      stratified epithelia to study the K14 functions in epithelial homeostasis. The
      K14 knockdown clones demonstrated substantial decreases in the levels of the K14
      partner K5. These cells showed reduction in cell proliferation and delay in cell
      cycle progression, along with decreased phosphorylated Akt levels. K14 knockdown
      cells also exhibited enhanced levels of activated Notch1, involucrin, and K1. In
      addition, K14 knockdown AW13516 cells showed significant reduction in
      tumorigenicity. Our results suggest that K5 and K14 may have a role in
      maintenance of cell proliferation potential in the basal layer of stratified
      epithelia, modulating phosphatidylinositol 3-kinase/Akt-mediated cell
      proliferation and/or Notch1-dependent cell differentiation.

PMID- 21900501
TI  - The SHP-1 protein tyrosine phosphatase negatively modulates Akt signaling in the
      ghrelin/GHSR1a system.
AB  - The aim of the present study was to identify the signaling mechanism(s)
      responsible for the modulation of growth hormone secretagogue receptor type 1a
      (GHSR1a)-associated Akt activity. Ghrelin leads to the activation of Akt through
      the interplay of distinct signaling mechanisms: an early G(i/o) protein-dependent
      pathway and a late pathway mediated by beta-arrestins. We found that the Src
      homology 2-containing protein tyrosine phosphatase (SHP-1) was an essential
      molecule in both G(i/o) protein-dependent and beta-arrestin-mediated pathways.
      More specifically, the role of SHP-1 in the G(i/o) protein-dependent pathway was
      demonstrated by the fact that the overexpression of a catalytically defective SHP
      1 augments tyrosine phosphorylation of the PI3K regulatory subunit p85, leading
      to an increase in the phosphorylation of cSrc and phosphoinositide-dependent
      protein kinase 1, and finally activating Akt. The presence of SHP-1 in the beta
      arrestin-scaffolded complex and its attenuating effect on the cSrc and Akt
      activities verified that SHP-1 regulates not only the G(i/o) protein-dependent
      pathway but also the beta-arrestin-mediated pathway. Assays performed in
      preadipocyte and adipocyte 3T3-L1 cells showed SHP-1 expression. According to our
      results in HEK-GHSR1a cells, ghrelin stimulated SHP-1 phosphorylation in 3T3-L1
      cells. The increase in ghrelin-induced Akt activity was enhanced by small
      interfering RNA of SHP-1 in preadipocyte 3T3-L1 cells. These results were
      reproduced in white adipose tissue obtained from mice, in which SHP-1 exhibited
      higher expression in omental than in subcutaneous tissue. Furthermore, this
      pattern of expression was inverted in mice fed a high-fat diet, suggesting a role
      for SHP-1 in controlling ghrelin sensitivity in adipose tissue. Indeed, SHP-1
      deficiency was associated with augmented ghrelin-evoked Akt phosphorylation in
      omental tissue, as well as decreased phosphorylation under overexpression of SHP
      1 in subcutaneous tissue. These findings showed a novel role for SHP-1 in the
      regulation of Akt activity through the modulation of the ghrelin/GHSR1a system
      signaling.

PMID- 21900503
TI  - The Pot1a-associated proteins Tpt1 and Pat1 coordinate telomere protection and
      length regulation in Tetrahymena.
AB  - We have identified two new telomere proteins, Tpt1 and Pat1, from the ciliate
      Tetrahymena thermophila. Although Tetrahymena telomerase is well characterized,
      only one telomere protein had previously been identified. This was the G-overhang
      binding-protein Pot1a. Tpt1 and Pat1 were isolated as Pot1a binding partners and
      shown to localize to telomeres. As Tpt1 and Pat1 were both found to be essential,
      conditional cell lines were generated to explore their function. Tpt1 depletion
      caused a rapid growth arrest and telomere elongation in the absence of cell
      division. The phenotype was similar to that seen after Pot1a depletion suggesting
      that Tpt1 and Pot1a function together to regulate telomere length and prevent
      telomere deprotection. In contrast, Pat1 depletion had a modest effect on cell
      growth but caused progressive telomere shortening similar to that observed upon
      TERT depletion. Thus Pat1 appears to be needed for telomerase to maintain the
      chromosome terminus. Analysis of Pot1a-Tpt1-Pat1 complex formation using purified
      proteins indicated that Tpt1 interacts directly with Pot1a while Pat1 interacts
      with Tpt1. Our results indicate that Tpt1 is the Tetrahymena equivalent of
      mammalian TPP1, Schizosaccharomyces pombe Tpz1, and Oxytricha nova TEBPbeta.

PMID- 21900502
TI  - Munc18-1 domain-1 controls vesicle docking and secretion by interacting with
      syntaxin-1 and chaperoning it to the plasma membrane.
AB  - Munc18-1 plays pleiotropic roles in neurosecretion by acting as 1) a molecular
      chaperone of syntaxin-1, 2) a mediator of dense-core vesicle docking, and 3) a
      priming factor for soluble N-ethylmaleimide-sensitive factor attachment protein
      receptor-mediated membrane fusion. However, how these functions are executed and
      whether they are correlated remains unclear. Here we analyzed the role of the
      domain-1 cleft of Munc18-1 by measuring the abilities of various mutants (D34N,
      D34N/M38V, K46E, E59K, K46E/E59K, K63E, and E66A) to bind and chaperone syntaxin
      1 and to restore the docking and secretion of dense-core vesicles in Munc18-1/-2
      double-knockdown cells. We identified striking correlations between the abilities
      of these mutants to bind and chaperone syntaxin-1 with their ability to restore
      vesicle docking and secretion. These results suggest that the domain-1 cleft of
      Munc18-1 is essential for binding to syntaxin-1 and thereby critical for its
      chaperoning, docking, and secretory functions. Our results demonstrate that the
      effect of the alleged priming mutants (E59K, D34N/M38V) on exocytosis can largely
      be explained by their reduced syntaxin-1-chaperoning functions. Finally, our data
      suggest that the intracellular expression and distribution of syntaxin-1
      determines the level of dense-core vesicle docking.

PMID- 21900505
TI  - City governments and aging in place: community design, transportation and housing
      innovation adoption.
AB  - PURPOSE OF THE STUDY: To examine the characteristics associated with city
      government adoption of community design, housing, and transportation innovations
      that could benefit older adults. DESIGN AND METHODS: A mixed-methods study with
      quantitative data collected via online surveys from 62 city planners combined
      with qualitative data collected via telephone interviews with a subsample of 18
      survey respondents. RESULTS: Results indicate that advocacy is an effective
      strategy to encourage city government adoption of these innovations. Percent of
      the population with a disability was positively associated, whereas percent of
      the population aged 65 and older was not associated or negatively associated,
      with innovation adoption in the regression models. Qualitative interviews suggest
      that younger individuals with disabilities are more active in local advocacy
      efforts. IMPLICATIONS: Results suggest that successful advocacy strategies for
      local government adoption include facilitating the involvement of older
      residents, targeting key decision makers within government, emphasizing the
      financial benefits to the city, and focusing on cities whose aging residents are
      vulnerable to disease and disability.

PMID- 21900504
TI  - Membrane-targeted WAVE mediates photoreceptor axon targeting in the absence of
      the WAVE complex in Drosophila.
AB  - A tight spatial-temporal coordination of F-actin dynamics is crucial for a large
      variety of cellular processes that shape cells. The Abelson interactor (Abi) has
      a conserved role in Arp2/3-dependent actin polymerization, regulating Wiskott
      Aldrich syndrome protein (WASP) and WASP family verprolin-homologous protein
      (WAVE). In this paper, we report that Abi exerts nonautonomous control of
      photoreceptor axon targeting in the Drosophila visual system through WAVE. In abi
      mutants, WAVE is unstable but restored by reexpression of Abi, confirming that
      Abi controls the integrity of the WAVE complex in vivo. Remarkably, expression of
      a membrane-tethered WAVE protein rescues the axonal projection defects of abi
      mutants in the absence of the other subunits of the WAVE complex, whereas
      cytoplasmic WAVE only slightly affects the abi mutant phenotype. Thus complex
      formation not only stabilizes WAVE, but also provides further membrane-recruiting
      signals, resulting in an activation of WAVE.

PMID- 21900506
TI  - The pain of "chronic Lyme disease": moving the discourse in a different
      direction.
AB  - About 30% of the population of the United States suffers from acute or chronic
      pain, often of unknown cause. Among this group might be included patients with
      symptoms claimed to be caused by a poorly defined condition called "chronic Lyme
      disease" in which chronic pain is a major contributor. Since there is no evidence
      to indicate that chronic Lyme disease is due to a persistent infection and that
      extended antibiotic therapy is beneficial and safe, this condition should not be
      viewed solely as an infectious disease problem. Rather, it should be considered
      within the context of a broad-based, multidisciplinary approach to determining
      the cause of chronic pain per se and developing more effective strategies for its
      treatment as outlined in a recent report on pain issued by the Institute of
      Medicine.

PMID- 21900507
TI  - Expression and functional properties of TRPM2 channels in dopaminergic neurons of
      the substantia nigra of the rat.
AB  - Transient receptor potential melastatin 2 (TRPM2) channels are sensitive to
      oxidative stress, and their activation can lead to cell death. Although these
      channels have been extensively studied in expression systems, their role in the
      brain, particularly in the substantia nigra pars compacta (SNc), remains unknown.
      In this study, we assessed the expression and functional properties of TRPM2
      channels in rat dopaminergic SNc neurons, using acute brain slices. RT-PCR
      analysis revealed TRPM2 mRNA expression in the SNc region. Immunohistochemistry
      demonstrated expression of TRPM2 protein in tyrosine hydroxylase-positive
      neurons. Channel function was tested with whole cell patch-clamp recordings and
      calcium (fura-2) imaging. Intracellular application of ADP-ribose (50-400 MUM)
      evoked a dose-dependent, desensitizing inward current and intracellular free
      calcium concentration ([Ca(2+)](i)) rise. These responses were strongly inhibited
      by the nonselective TRPM2 channel blockers clotrimazole and flufenamic acid.
      Exogenous application of H(2)O(2) (1-5 mM) evoked a rise in [Ca(2+)](i) and an
      outward current mainly due to activation of ATP-sensitive potassium (K(ATP))
      channels. Inhibition of K(+) conductance with Cs(+) and tetraethylammonium
      unmasked an inward current. The inward current and/or [Ca(2+)](i) rise were
      partially blocked by clotrimazole and N-(p-amylcinnamoyl)anthranilic acid (ACA).
      The H(2)O(2)-induced [Ca(2+)](i) rise was abolished in "zero" extracellular
      Ca(2+) concentration and was enhanced at higher baseline [Ca(2+)](i), consistent
      with activation of TRPM2 channels in the cell membrane. These results provide
      evidence for the functional expression of TRPM2 channels in dopaminergic SNc
      neurons. Given the involvement of oxidative stress in degeneration of SNc neurons
      in Parkinson's disease, further studies are needed to determine the
      pathophysiological role of these channels in the disease process.

PMID- 21900508
TI  - Endogenous modulation of low frequency oscillations by temporal expectations.
AB  - Recent studies have associated increasing temporal expectations with
      synchronization of higher frequency oscillations and suppression of lower
      frequencies. In this experiment, we explore a proposal that low-frequency
      oscillations provide a mechanism for regulating temporal expectations. We used a
      speeded Go/No-go task and manipulated temporal expectations by changing the
      probability of target presentation after certain intervals. Across two
      conditions, the temporal conditional probability of target events differed
      substantially at the first of three possible intervals. We found that reactions
      times differed significantly at this first interval across conditions, decreasing
      with higher temporal expectations. Interestingly, the power of theta activity (4
      8 Hz), distributed over central midline sites, also differed significantly across
      conditions at this first interval. Furthermore, we found a transient coupling
      between theta phase and beta power after the first interval in the condition with
      high temporal expectation for targets at this time point. Our results suggest
      that the adjustments in theta power and the phase-power coupling between theta
      and beta contribute to a central mechanism for controlling neural excitability
      according to temporal expectations.

PMID- 21900510
TI  - Individual and synergistic effects of sniffing frequency and flow rate on
      olfactory bulb activity.
AB  - Is faster or stronger sniffing important for the olfactory system? Odorant
      molecules are captured by sniffing. The features of sniffing constrain both the
      temporality and intensity of the input to the olfactory structures. In this
      context, it is clear that variations in both the sniff frequency and flow rate
      have a major impact on the activation of olfactory structures. However, the
      question of how frequency and flow rate individually or synergistically impact
      bulbar output has not been answered. We have addressed this question using
      multiple experimental approaches. In double-tracheotomized, anesthetized rats, we
      recorded both the bulbar local field potential (LFP) and mitral/tufted cells'
      activities when the sampling flow rate and frequency were controlled
      independently. We found that a tradeoff between the sampling frequency and the
      flow rate could maintain olfactory bulb sampling-related rhythmicity and that
      only an increase in flow rate could induce a faster, odor-evoked response. LFP
      and sniffing were recorded in awake rats. We found that sampling-related
      rhythmicity was maintained during high-frequency sniffing. Furthermore, we
      observed that the covariation between the frequency and flow rate, which was
      necessary for the tradeoff seen in the anesthetized preparations, also occurred
      in awake animals. Our study shows that the sampling frequency and flow rate can
      act either independently or synergistically on bulbar output to shape the
      neuronal message. The system likely takes advantage of this flexibility to adapt
      sniffing strategies to animal behavior. Our study provides additional support for
      the idea that sniffing and olfaction function in an integrated manner.

PMID- 21900509
TI  - TRPM8 acute desensitization is mediated by calmodulin and requires PIP(2):
      distinction from tachyphylaxis.
AB  - The cold-sensing channel transient receptor potential melastatin 8 (TRPM8)
      features Ca(2+)-dependent downregulation, a cellular process underlying
      somatosensory accommodation in cold environments. The Ca(2+)-dependent functional
      downregulation of TRPM8 is manifested with two distinctive phases, acute
      desensitization and tachyphylaxis. Here we show in rat dorsal root ganglion
      neurons that TRPM8 acute desensitization critically depends on
      phosphatidylinositol 4,5-bisphosphate (PIP(2)) availability rather than PIP(2)
      hydrolysis and is triggered by calmodulin activation. Tachyphylaxis, on the other
      hand, is mediated by phospholipase hydrolysis of PIP(2) and protein kinase
      C/phosphatase 1,2A. We further demonstrate that PIP(2) switches TRPM8 channel
      gating to a high-open probability state with short closed times. Ca(2+)
      calmodulin reverses the effect of PIP(2), switching channel gating to a low-open
      probability state with long closed times. Thus, through gating modulation, Ca(2+)
      calmodulin provides a mechanism to rapidly regulate TRPM8 functions in the
      somatosensory system.

PMID- 21900511
TI  - Identification of single neurons in a forebrain network.
AB  - Behaviors are generated from complex interactions among networks of neurons.
      Single-unit ensemble recording has been used to identify multiple neurons in
      functioning networks. These recordings have provided insight into interactions
      among neurons in local and distributed circuits. Recorded units in these
      ensembles have been classed based on waveform type, firing pattern, and physical
      location. To identify individual projection neurons in a cortical network, we
      have paired tetrode recording with antidromic stimulation. We developed
      techniques that enable antidromic identification of single units and study of
      functional interactions between these neurons and other circuit elements. These
      methods have been developed in the zebra finch and should be applicable, with
      potential modifications that we discuss here, to any neural circuit with defined
      subpopulations based on projection target. This methodology will enable
      elucidation of the functional roles of single identified neurons in complex
      vertebrate circuits.

PMID- 21900512
TI  - Astrocytes promote peripheral nerve injury-induced reactive synaptogenesis in the
      neonatal CNS.
AB  - Neonatal damage to the trigeminal nerve leads to "reactive synaptogenesis" in the
      brain stem sensory trigeminal nuclei. In vitro models of brain injury-induced
      synaptogenesis have implicated an important role for astrocytes. In this study we
      tested the role of astrocyte function in reactive synaptogenesis in the
      trigeminal principal nucleus (PrV) of neonatal rats following unilateral
      transection of the infraorbital (IO) branch of the trigeminal nerve. We used
      electrophysiological multiple input index analysis (MII) to estimate the number
      of central trigeminal afferent fibers that converge onto single barrelette
      neurons. In the developing PrV, about 30% of afferent connections are eliminated
      within 2 postnatal weeks. After neonatal IO nerve damage, multiple trigeminal
      inputs (2.7 times that of the normal inputs) converge on single barrelette cells
      within 3-5 days; they remain stable up to the second postnatal week. Astrocyte
      proliferation and upregulation of astrocyte-specific proteins (GFAP and ALDH1L1)
      accompany reactive synaptogenesis in the IO nerve projection zone of the PrV.
      Pharmacological blockade of astrocyte function, purinergic receptors, and
      thrombospondins significantly reduced or eliminated reactive synaptogenesis
      without changing the MII in the intact PrV. GFAP immunohistochemistry further
      supported these electrophysiological results. We conclude that immature
      astrocytes, purinergic receptors, and thrombospondins play an important role in
      reactive synaptogenesis in the peripherally deafferented neonatal PrV.

PMID- 21900513
TI  - Flexible interpretation of a decision rule by supplementary eye field neurons.
AB  - Since the environment is in constant flux, decision-making capabilities of the
      brain must be rapid and flexible. Yet in sensory motion processing pathways of
      the primate brain where decision making has been extensively studied, the
      flexibility of neurons is limited by inherent selectivity to motion direction and
      speed. The supplementary eye field (SEF), an area involved in decision making on
      moving stimuli, is not strictly a sensory or motor structure, and hence may not
      suffer such limitations. Here we test whether neurons in the SEF can flexibly
      interpret the rule of a go/nogo task when the decision boundary in the task
      changes with each trial. The task rule specified that the animal pursue a moving
      target with its eyes if and when the target entered a visible zone. The size of
      the zone was changed from trial to trial in order to shift the decision boundary,
      and thereby assign different go/nogo significance to the same motion
      trajectories. Individual SEF neurons interpreted the rule appropriately,
      signaling go or nogo in compliance with the rule and not the direction of motion.
      The results provide the first evidence that individual neurons in frontal cortex
      can flexibly interpret a rule that governs the decision to act.

PMID- 21900514
TI  - Long-duration perforated patch recordings from spinal interneurons of adult mice.
AB  - It has been very difficult to record from interneurons in acute slices of the
      lumbar spinal cord from mice >3 wk of age. The low success rate and short
      recording times limit in vitro experimentation on mouse spinal networks to
      neonatal and early postnatal periods when locomotor networks are still
      developmentally immature. To overcome this limitation and enable investigation of
      mature locomotor network neurons, we have established a reliable procedure to
      record from spinal cord neurons in slices from adult, behaviorally mature mice of
      any age. Two key changes to the established neonate procedure were implemented.
      First, we remove the cord by a dorsal laminectomy from a deeply anesthetized
      animal. This enables respiration and other vital functions to continue up to the
      moment the maximally oxygenated lumbar spinal cord is removed, improving the
      health of the slices. Second, since adult spinal cord interneurons appear more
      sensitive to the intracellular dialysis that occurs during whole cell recordings,
      we introduced perforated patch recordings to the procedure. Stable recordings up
      to 12 h in duration were obtained with our new method. This will allow
      investigation of changes in mature neuronal properties in disease states or after
      spinal cord injury and allow prolonged recordings of responses to drug
      application that were previously impossible.

PMID- 21900515
TI  - Haemophilus influenzae infections in the H. influenzae type b conjugate vaccine
      era.
AB  - The widespread use of Haemophilus influenzae type b (Hib) conjugate vaccines has
      nearly eradicated invasive Hib disease where the vaccines are used. This success
      was accompanied by a shift in capsular serotypes of invasive H. influenzae
      disease, with nontypeable strains replacing type b strains as the most common
      bloodstream isolate, but there is no convincing evidence of a true increase in
      the incidence of non-serotype b invasive infections. H. influenzae causes
      predominantly mucosal infections. The introduction of vaccines for otitis media
      and global shifts in antimicrobial susceptibility emphasize the importance of
      continued surveillance of H. influenzae colonization and disease patterns.

PMID- 21900516
TI  - Recovery of a catalase-negative Staphylococcus epidermidis strain in blood and
      urine cultures from a patient with pyelonephritis.
AB  - This report describes a 60-year-old patient with bilateral nephrolithiasis. A
      catalase-negative Staphylococcus epidermidis strain was recovered from both urine
      and blood cultures. Although rare, isolates of catalase-negative Staphylococcus
      spp., including Staphylococcus aureus, have been reported. Here, we describe the
      first report of a catalase-negative S. epidermidis strain.

PMID- 21900517
TI  - Three-locus identification, genotyping, and antifungal susceptibilities of
      medically important Trichosporon species from China.
AB  - Three reference and 45 clinical isolates of Trichosporon were analyzed by
      conventional phenotypic and molecular methods to determine the species and
      genotypes of Trichosporon isolates from China. Target loci for molecular methods
      included the internal transcribed spacer (ITS) region, the D1/D2 domain of the
      26S rRNA gene, and the intergenic spacer 1 (IGS1) region. Identification of eight
      Trichosporon species was achieved, of which Trichosporon asahii was the most
      common. Of the sequence-based molecular methods, the one targeting the D1/D2
      domain assigned 97.9% (47/48) of isolates (seven species) correctly, while tests
      targeting both the ITS and IGS1 regions correctly identified all 48 isolates. The
      commercial API 20C AUX and Vitek 2 Compact YST systems correctly identified 91.9%
      and 73% of isolates when their biochemical profiles were queried against those of
      species contained in the databases, respectively, and misidentified 63.6% and
      36.4% of isolates of species that were unclaimed by the databases, respectively.
      The predominant genotype among T. asahii clinical isolates, genotype 4 (51.4%),
      is rarely found in other countries. Voriconazole and itraconazole were the most
      active drugs in vitro against all the Trichosporon species tested, while
      caspofungin and amphotericin B demonstrated poor activity.

PMID- 21900519
TI  - Triazole and echinocandin MIC distributions with epidemiological cutoff values
      for differentiation of wild-type strains from non-wild-type strains of six
      uncommon species of Candida.
AB  - When clinical susceptibility breakpoints (CBPs) are absent, establishing wild
      type (WT) MIC distributions and epidemiological cutoff values (ECVs) provides a
      sensitive means for detecting emerging resistance. We determined species-specific
      ECVs for anidulafungin (ANF), caspofungin (CSF), micafungin (MCF), fluconazole
      (FLC), posaconazole (PSC), and voriconazole (VRC) for six rarer Candida species
      (819 strains) using isolates obtained from the ARTEMIS Program and the SENTRY
      Antimicrobial Surveillance Program, all tested by a reference broth microdilution
      method. The calculated ECVs, expressed in MUg/ml (and the percentages of isolates
      that had MICs less than or equal to the ECVs), for ANF, CSF, MCF, FLC, PSC, and
      VRC, respectively, were 0.12 (95.2), 0.12 (97.8), 0.12 (100.0), 0.5 (95.7), 0.12
      (98.6), and 0.03 (100.0) for Candida dubliniensis; 4 (100.0), 2 (96.0), 2 (99.1),
      8 (95.0), 0.5 (97.5), and 0.25 (98.0) for C. guilliermondii; 0.25 (98.9), 0.03
      (98.0), 0.12 (97.5), 1 (99.1), 0.25 (99.1), and 0.015 (100.0) for C. kefyr; 2
      (100.0), 1 (99.6), 0.5 (96.6), 2 (96.1), 0.25 (98.6), and 0.03 (96.6) for C.
      lusitaniae; and 2 (100.0), 0.5 (100.0), 1 (100.0), 2 (98.0), 0.25 (97.1), and
      0.06 (98.0) for C. orthopsilosis, but for C. pelliculosa, ECVs could be
      determined only for CSF (0.12 [94.4]), FLC (4 [98.2]), PSC (2 [98.2]), and VRC
      (0.25 [98.2]). In the absence of species-specific CBP values, these WT MIC
      distributions and ECVs will be useful for monitoring the emergence of reduced
      susceptibility to the triazole and echinocandin antifungals.

PMID- 21900518
TI  - Viral-bacterial interactions and risk of acute otitis media complicating upper
      respiratory tract infection.
AB  - Acute otitis media (AOM) is a common complication of upper respiratory tract
      infection whose pathogenesis involves both viruses and bacteria. We examined
      risks of acute otitis media associated with specific combinations of respiratory
      viruses and acute otitis media bacterial pathogens. Data were from a prospective
      study of children ages 6 to 36 months and included viral and bacterial culture
      and quantitative PCR for respiratory syncytial virus (RSV), human bocavirus, and
      human metapneumovirus. Repeated-measure logistic regression was used to assess
      the relationship between specific viruses, bacteria, and the risk of acute otitis
      media complicating upper respiratory tract infection. In unadjusted analyses of
      data from 194 children, adenovirus, bocavirus, Streptococcus pneumoniae,
      Haemophilus influenzae, and Moraxella catarrhalis were significantly associated
      with AOM (P < 0.05 by chi(2) test). Children with high respiratory syncytial
      virus loads (>=3.16 * 10(7) copies/ml) experienced increased acute otitis media
      risk. Higher viral loads of bocavirus and metapneumovirus were not significantly
      associated with acute otitis media. In adjusted models controlling for the
      presence of key viruses, bacteria, and acute otitis media risk factors, acute
      otitis media risk was independently associated with high RSV viral load with
      Streptococcus pneumoniae (odds ratio [OR], 4.40; 95% confidence interval [CI],
      1.90 and 10.19) and Haemophilus influenzae (OR, 2.04; 95% CI, 1.38 and 3.02). The
      risk was higher for the presence of bocavirus and H. influenzae together (OR,
      3.61; 95% CI, 1.90 and 6.86). Acute otitis media risk differs by the specific
      viruses and bacteria involved. Acute otitis media prevention efforts should
      consider methods for reducing infections caused by respiratory syncytial virus,
      bocavirus, and adenovirus in addition to acute otitis media bacterial pathogens.

PMID- 21900520
TI  - Rapid PCR-based molecular pathotyping of H5 and H7 avian influenza viruses.
AB  - While the majority of avian influenza virus (AIV) subtypes are classified as low
      pathogenicity avian influenza viruses (LPAIV), the H5 and H7 subtypes have the
      ability to mutate to highly pathogenic avian influenza viruses (HPAIV) in poultry
      and therefore are the etiological agents of notifiable AIV (NAIV). It is of great
      importance to distinguish HPAIV from LPAIV variants during H5/H7 outbreaks and
      surveillance. To this end, a novel and fast strategy for the molecular
      pathotyping of H5/H7 AIVs is presented. The differentiation of the characteristic
      hemagglutinin (HA) protein cleavage sites (CSs) of HPAIVs and LPAIVs is achieved
      by a novel PCR method where the samples are interrogated for all existing CSs
      with a 484-plex primer mixture directly targeting the CS region. CSs
      characteristic for HP or LP H5/H7 viruses are distinguished in a seminested
      duplex real-time PCR format using plexor fluorogenic primers. Eighty-six
      laboratory isolates and 60 characterized NAIV-positive clinical specimens from
      poultry infected with H5/H7 both experimentally and in the field were
      successfully pathotyped in the validation. The method has the potential to
      substitute CS sequencing in the HA gene for the determination of the molecular
      pathotype, thereby providing a rapid means to acquire additional information
      concerning NAIV outbreaks, which may be critical to their management. The new
      assay may be extended to the LP/HP differentiation of previously unknown H5/H7
      isolates. It may be considered for integration into surveillance and control
      programs in both domestic and wild bird populations.

PMID- 21900521
TI  - Molecular typing and virulence analysis of serotype K1 Klebsiella pneumoniae
      strains isolated from liver abscess patients and stool samples from noninfectious
      subjects in Hong Kong, Singapore, and Taiwan.
AB  - Serotype K1 Klebsiella pneumoniae with multilocus sequence type 23 (ST23) has
      been strongly associated with liver abscess in Taiwan. Few data regarding the
      strain types and virulence of this serotype from other Asian countries are
      available. Serotype K1 K. pneumoniae strains isolated from liver abscess and
      stool samples from subjects hospitalized in Hong Kong, Singapore, and Taiwan
      hospitals were examined. Forty-seven serotype K1 isolates were identified: 26
      from liver abscess samples and 21 from stool samples. MLST revealed 7 sequence
      types: 85.1% (40 of 47 isolates) belonged to ST23, 1 isolate belonged to ST163 (a
      single-locus variant of ST23), and 2 isolates were ST249 (a 3-locus variant of
      ST23). New STs, namely, ST367, ST425, and ST426, were allocated to 3 of 4
      isolates from stool samples. The virulence of these strains was determined by
      neutrophil phagocytosis and mouse infection models. Except for two ST23 isolates,
      all Klebsiella pneumoniae isolates were resistant to phagocytosis. Resistance to
      serum killing varied in isolates of ST23, while all non-ST23 strains were
      susceptible to serum killing except one with ST249 from a liver abscess. All
      hypervirulent isolates with a 50% lethal dose of <10(2) CFU were from ST23, were
      resistant to phagocytosis and serum killing, and also carried both virulence
      associated genes, rmpA and aerobactin. Multilocus sequence typing genotype 23 was
      the most prevalent sequence type among serotype K1 K. pneumoniae isolates from
      both liver abscess and stool samples in the Asia Pacific region. Serotype K1 K.
      pneumoniae isolates with capsule expression leading to phagocytic resistance and
      with the aerobactin gene were associated with hypervirulence.

PMID- 21900522
TI  - Molecular bacterial load assay, a culture-free biomarker for rapid and accurate
      quantification of sputum Mycobacterium tuberculosis bacillary load during
      treatment.
AB  - A molecular assay to quantify Mycobacterium tuberculosis is described. In vitro,
      98% (n = 96) of sputum samples with a known number of bacilli (10(7) to 10(2)
      bacilli) could be enumerated within 0.5 log(10). In comparison to culture, the
      molecular bacterial load (MBL) assay is unaffected by other microorganisms
      present in the sample, results are obtained more quickly (within 24 h) and are
      seldom inhibited (0.7% samples), and the MBL assay critically shows the same
      biphasic decline as observed longitudinally during treatment. As a biomarker of
      treatment response, the MBL assay responds rapidly, with a mean decline in
      bacterial load for 111 subjects of 0.99 log(10) (95% confidence interval [95%
      CI], 0.81 to 1.17) after 3 days of chemotherapy. There was a significant
      association between the rate of bacterial decline during the same 3 days and
      bacilli ml(-1) sputum at day 0 (linear regression, P = 0.0003) and a 3.62
      increased odds ratio of relapse for every 1 log(10) increase in pretreatment
      bacterial load (95% CI, 1.53 to 8.59).

PMID- 21900523
TI  - Detection of an influenza B virus strain with reduced susceptibility to
      neuraminidase inhibitor drugs.

PMID- 21900524
TI  - Independent emergence of colistin-resistant Enterobacteriaceae clinical isolates
      without colistin treatment.

PMID- 21900525
TI  - Containment of an outbreak of KPC-3-producing Klebsiella pneumoniae in Italy.
AB  - From March 2009 to May 2009, 24 carbapenem-resistant Klebsiella pneumoniae
      isolates were recovered from 16 patients hospitalized in an Italian intensive
      care unit (ICU). All isolates contained KPC-3 carbapenemase and belonged to a
      single pulsed-field gel electrophoresis (PFGE) clone of multilocus sequence type
      258 (designated as ST258). A multimodal infection control program was put into
      effect, and the spread of the KPC-3-producing K. pneumoniae clone was ultimately
      controlled without closing the ICU to new admissions. Reinforced infection
      control measures and strict monitoring of the staff adherence were necessary for
      the control of the outbreak.

PMID- 21900526
TI  - Assessment of Lactobacillus gasseri as a candidate oral vaccine vector.
AB  - Lactobacillus species are commensal bacteria that have long been recognized as
      probiotic microbes and are generally regarded as safe (GRAS) for human
      consumption. We have investigated the use of L. gasseri as a vaccine vector for
      oral immunization against mucosal pathogens. Recent research has shown that the
      immune response to different lactobacilli can vary widely depending on the
      species or subspecies of Lactobacillus being studied. While some lactobacilli
      seem to induce oral tolerance, others induce an adaptive immune response. This
      study characterized the systemic and mucosal immune response to wild-type and
      genetically modified L. gasseri. L. gasseri primarily activates TLR2/6, with
      additional activation through the TLR2 homodimer. To expand the Toll-like
      receptor (TLR) activation profile of L. gasseri and the immunogenicity of the
      vector, a plasmid containing fliC, the gene encoding bacterial flagellin, was
      introduced which resulted in the strong activation of TLR5. The treatment of
      human myeloid dendritic cells with recombinant lactobacilli expressing flagellin
      triggered phenotypic maturation and the release of proinflammatory cytokines. In
      contrast, bacterial treatment also resulted in a statistically significant
      increase in IL-10 production. In vivo studies established that treatment with L.
      gasseri led to a diversification of B-cell populations in the lamina propria of
      the murine colon. Furthermore, treatment with genetically modified L. gasseri led
      to a significant decrease in the percentage of FoxP3(+) colonic lymphocytes.
      Taken together, these data clarify the interaction of L. gasseri with the host
      immune system and support further investigation of the in vivo immunogenicity of
      L. gasseri expressing both flagellin and candidate vaccine antigens.

PMID- 21900527
TI  - Oral immunization with recombinant Mycobacterium smegmatis expressing the outer
      membrane protein 26-kilodalton antigen confers prophylactic protection against
      Helicobacter pylori infection.
AB  - Helicobacter pylori infection is prevalent worldwide and results in chronic
      gastritis, which may lead to gastric mucosa-associated lymphoid tissue lymphoma
      and gastric cancer. We have previously reported that oral immunization with
      recombinant Mycobacterium smegmatis expressing the H. pylori outer membrane
      protein 26-kilodalton (Omp26) antigen affords therapeutic protection against H.
      pylori infection in mice. In the present study, we investigated the prophylactic
      effects of this vaccine candidate on H. pylori challenge in mice. We found that
      oral immunization with recombinant Mycobacterium Omp26 significantly reduced H.
      pylori colonization in the stomach compared to inoculation with wild-type M.
      smegmatis in control mice. Six of the recombinant Mycobacterium-immunized mice
      (60%) were completely protected from H. pylori infection. The severity of H.
      pylori-associated chronic gastritis assessed histologically was significantly
      milder in mice vaccinated with recombinant Mycobacterium than in control animals.
      Mice immunized with recombinant Mycobacterium showed enhanced antigen-specific
      lymphocyte proliferation and antibody responses. Moreover, immunization with
      recombinant Mycobacterium resulted in an increased expression of interleukin-2
      and gamma interferon in the stomach and spleen, as determined by reverse
      transcription-PCR analysis. Our results collectively suggest that vaccination
      with recombinant Mycobacterium Omp26 confers prophylactic protection against H.
      pylori infection. The inhibition of H. pylori colonization is associated with the
      induction of antigen-specific humoral and cell-mediated immune responses.

PMID- 21900528
TI  - Concomitant administration of Mycobacterium bovis BCG with the meningococcal C
      conjugate vaccine to neonatal mice enhances antibody response and protective
      efficacy.
AB  - Mycobacterium bovis BCG is administered to human neonates in many countries
      worldwide. The objective of the study was to assess if BCG could act as an
      adjuvant for polysaccharide-protein conjugate vaccines in newborns and thereby
      induce protective immunity against encapsulated bacteria in early infancy when
      susceptibility is high. We assessed whether BCG could enhance immune responses to
      a meningococcal C (MenC) conjugate vaccine, MenC-CRM(197), in mice primed as
      neonates, broaden the antibody response from a dominant IgG1 toward a mixed IgG1
      and IgG2a/IgG2b response, and increase protective efficacy, as measured by serum
      bactericidal activity (SBA). Two-week-old mice were primed subcutaneously (s.c.)
      with MenC-CRM(197). BCG was administered concomitantly, a day or a week before
      MenC-CRM(197). An adjuvant effect of BCG was observed only when it was given
      concomitantly with MenC-CRM(197), with increased IgG response (P = 0.002) and SBA
      (8-fold) after a second immunization with MenC-CRM(197) without BCG, indicating
      increased T-cell help. In neonatal mice (1 week old) primed s.c. with MenC
      CRM(197) together with BCG, MenC-polysaccharide (PS)-specific IgG was enhanced
      compared to MenC-CRM(197) alone (P = 0.0015). Sixteen days after the second
      immunization with MenC-CRM(197), increased IgG (P < 0.05), IgG1 (P < 0.05), IgG2a
      (P = 0.06), and IgG2b (P < 0.05) were observed, and only mice primed with MenC
      CRM(197) plus BCG showed affinity maturation and detectable SBA (SBA > 128).
      Thus, vaccination with a meningococcal conjugate vaccine (and possibly with other
      conjugates) may benefit from concomitant administration of BCG in the neonatal
      period to accelerate and enhance production of protective antibodies, compared to
      the current infant administration of conjugate which follows BCG vaccination at
      birth.

PMID- 21900529
TI  - Development of an automated and multiplexed serotyping assay for Streptococcus
      pneumoniae.
AB  - Streptococcus pneumoniae expresses more than 90 capsule types, and currently
      available pneumococcal vaccines are designed to provide serotype-specific
      protection. Consequently, serotyping of pneumococcal isolates is important for
      determining the serotypes to be included in pneumococcal vaccines and to monitor
      their efficacy. Yet serotyping of pneumococcal isolates has remained a
      significant technical challenge. By multiplexing many assays, we have now
      developed a simple yet comprehensive serotyping assay system that can not only
      identify all known pneumococcal serotypes but also subdivide nontypeable (NT)
      isolates into those with or without the conventional capsule locus. We have
      developed this assay system to require only six key reagents: two are used in one
      multiplex inhibition-type immunoassay, and four are required in two multiplex PCR
      based assays. The assay system is largely automated by a seamless combination of
      monoclonal antibody-based and PCR-based multiplex assays using the flow
      cytometric bead array technology from Luminex. The assay system has been
      validated with a panel of pneumococci expressing all known pneumococcal serotypes
      and was found to be easily transferable to another laboratory.

PMID- 21900530
TI  - Outer membrane vesicles induce immune responses to virulence proteins and protect
      against colonization by enterotoxigenic Escherichia coli.
AB  - Enterotoxigenic Escherichia coli (ETEC) strains are a heterogeneous group of
      pathogens that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins.
      Collectively, these pathogens are responsible for hundreds of thousands of deaths
      annually in developing countries, particularly in children under the age of 5
      years. The heterogeneity of previously investigated molecular targets and the
      lack of complete sustained protection afforded by antitoxin immunity have impeded
      progress to date toward a broadly protective vaccine. Many pathogens, including
      ETEC, have the capacity to form outer membrane vesicles (OMV), which often
      contain one or more virulence proteins. Prompted by recent studies that
      identified several immunogenic virulence proteins in outer membrane vesicles of
      ETEC, we sought to examine the immunogenicity and protective efficacy of these
      structures in a murine model of infection. Here we demonstrate that immunization
      with OMV impairs ETEC colonization of the small intestine and stimulates
      antibodies that recognize the heat-labile toxin and two additional putative
      virulence proteins, the EtpA adhesin and CexE. Similar to earlier studies with
      EtpA, vaccination with LT alone also inhibited intestinal colonization. Together,
      these findings suggest that OMV could be exploited to deliver protective antigens
      relevant to development of ETEC vaccines.

PMID- 21900531
TI  - Can HIV p24 be a suitable scaffold for presenting Env antigens?

PMID- 21900532
TI  - High incidence of severe influenza among individuals over 50 years of age.
AB  - Age-specific epidemiological data on asymptomatic, symptomatic, and severe
      infections are essential for public health policies on combating influenza. In
      this study, we incorporated data on microbiologically confirmed infections and
      seroprevalence to comprehensively describe the epidemiology of pandemic H1N1 2009
      influenza. Seroprevalence was determined from 1,795 random serum samples
      collected in our hospital in January 2007 (before the first wave of the pandemic)
      and March 2010 (after the second wave). Data on microbiologically confirmed
      infection and severe cases were obtained from the Centre for Health Protection in
      Hong Kong. Severe cases were most common in the 51- to 60-year-old age group. The
      microbiologically confirmed incidence rate was highest for children aged <=10
      years and dropped sharply for the adult population (rho = -1.0; P < 0.01), but
      the incidence rate for severe disease was highest for the 51- to 60-year-old age
      group. For the 51- to 60-year-old age group, the seroprevalence was similar to
      that for the younger age groups, but the proportion of severe cases relative to
      seroprevalence was significantly higher than that for 11- to 50-year-old age
      groups. As judged from the percentage of specimens positive for other respiratory
      viruses compared with that for pandemic H1N1 virus, the impact of symptomatic
      disease due to pandemic H1N1 virus was higher than that for other respiratory
      viruses in people aged <=50 years. In conclusion, the 51- to 60-year-old age
      group, which had the highest overall incidence and the highest rate of severe
      disease but is currently not considered by the World Health Organization to be an
      at-risk group, should be prioritized for influenza vaccination in areas where
      universal influenza vaccination is not practiced.

PMID- 21900533
TI  - Immunization of mice with Lactobacillus casei expressing a beta-intimin fragment
      reduces intestinal colonization by Citrobacter rodentium.
AB  - Enteropathogenic Escherichia coli (EPEC) is a common cause of diarrhea in
      children from developing countries. Intimate adhesion of the bacteria to
      intestinal cells occurs via binding of the adhesin intimin to the TIR receptor
      exposed on cell surfaces. Here, Lactobacillus casei expressing a fragment of beta
      intimin (L. casei-Int(cv)) was tested as mucosal vaccines in mice against
      intestinal colonization with the murine pathogen Citrobacter rodentium. Oral or
      sublingual immunization of C57BL/6 mice with L. casei-Int(cv) induced anti
      Int(cv) IgA in feces but no IgG in sera. Conversely, anti-Int(cv) IgG was induced
      in the sera of mice after sublingual immunization with purified Int(cv). All
      vaccines were able to decrease C. rodentium recovery from feces. However, this
      reduction was more evident and sustained over time in mice immunized with L.
      casei-Int(cv) by the sublingual route. These mice also displayed an increase in
      interleukin 6 (IL-6) and gamma interferon (IFN-gamma) secretion by spleen cells
      10 days after infection. Additionally, oral or sublingual immunization of
      C3H/HePas mice, which are highly susceptible to C. rodentium infection, with L.
      casei-Int(cv) induced anti-Int(cv) antibodies and significantly increased
      survival after challenge. Immunohistological analysis of colon sections revealed
      that C. rodentium was located in deep fractions of the tissue from C3H/HePas mice
      immunized with L. casei whereas superficial staining was observed in colon
      sections from mice immunized with L. casei-Int(cv.) The results indicate that
      vaccines composed of L. casei expressing intimin may represent a promising
      approach and that the C3H/HePas infection model with C. rodentium can be used to
      evaluate potential vaccines against EPEC.

PMID- 21900535
TI  - Enhanced effect of DNA immunization plus in vivo electroporation with a
      combination of hepatitis B virus core-PreS1 and S-PreS1 plasmids.
AB  - To develop a novel, effective HBV therapeutic vaccine, we constructed two HBV DNA
      immunogens that contained PreS1, HBSS1, and HBCS1. Several delivery methods, such
      as intramuscular (i.m.) injection, intramuscular injection plus electroporation
      (i.m.-EP), and intradermal injection plus electroporation (i.d.-EP) were used in
      a murine model to analyze and compare the immune responses that were induced by
      the DNA immunogens. We found that i.d.-EP accelerated specific antibody
      seroconversion and produced high antibody (anti-PreS1, anti-S, and anti-C
      antibody) titers after HBSS1 and HBCS1 immunization. Combining the HBSS1 and
      HBCS1 DNA immunogens with i.d.-EP produced the strongest multiantigen (PreS1, S,
      and C)-specific cellular immune response and the highest specific PreS1 antibody
      levels. The results indicated that DNA immunization using HBSS1 and HBCS1 might
      be an ideal candidate, with its ability to elicit robust B and T cell immune
      responses against multiantigen when combined with optimized delivery technology.
      The present study provides a basis for the design and rational application of a
      novel HBV DNA vaccine.

PMID- 21900536
TI  - Do silicone nasal septal splints with integral airway reduce postoperative
      eustachian tube dysfunction?
AB  - OBJECTIVE: This study aims to compare the effects of Merocel nasal packs and
      silicone nasal septal splints with integral airway on the ventilation and
      pressure of the middle ear when applied intranasally after septoplasty for
      isolated septal deviation. STUDY DESIGN: A prospective, randomized trial.
      SETTING: A tertiary referral center. SUBJECTS AND METHODS: Fifty-one patients who
      underwent septoplasty for nasal respiratory impairment caused by septal deviation
      were randomized into 2 groups. After septoplasty, bilateral anterior Merocel
      nasal packs were applied in one group, while silicone nasal septal splints with
      integral airway were applied in the other group. Middle ear pressures were
      compared using preoperative and post-operative tympanometry. RESULTS:
      Pathological decrease in the middle ear pressure in at least 1 ear was determined
      in 17 patients (73.9%) in the Merocel group compared with only 6 patients (21.4%)
      in the silicone nasal septal splint group at the 48th postoperative hour. In the
      first 24 hours following surgery, decreases in tympanometric pressures were seen
      in both groups, but more in the Merocel group. After 24 hours, middle ear
      pressures continued to decrease in the Merocel group but started to increase in
      the silicone nasal septal splint group. CONCLUSION: Because they allow inhalation
      through the nose and cause less Eustachian tube dysfunction than Merocel, using
      silicone nasal septal splints with integral airway instead of packing after
      septoplasty seems a more reasonable option.

PMID- 21900537
TI  - Predictors of surgical outcomes of uvulopalatopharyngoplasty for obstructive
      sleep apnea hypopnea syndrome.
AB  - OBJECTIVES: To investigate predictors of surgical outcomes of
      uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea hypopnea syndrome
      (OSAHS). STUDY DESIGN: Case series with planned data collection. SETTING: A
      university medical center. SUBJECTS AND METHODS: Thirty-nine patients with OSAHS
      received Z-palatopharyngoplasty (ZPPP) or Han-uvulopalatopharyngoplasty (H-UPPP).
      All patients were evaluated within 3 months before surgery and at 6 to 12 months
      after surgery. Statistical analyses were conducted on preoperative parameters
      that could have affected surgical efficacy and outcome. Success was defined as an
      apnea-hypopnea index (AHI) fewer than 20 times per hour and a decrease of more
      than 50%. RESULTS: The success rate was 56.4% (22/39 patients). There were
      statistically significant differences in AHI, lowest oxygen saturation (L
      Sao(2)), time with oxygen saturation less than 90% (CT90), percentage of time
      with oxygen saturation less than 90% (CT90%), microarousal index (MI),
      apolipoprotein E (ApoE), high-density lipoprotein (HDL), fasting blood glucose
      (FBG), and Friedman OSA stage between the treatment success and failure groups.
      Higher success rate was predicted by lower severity, as indicated by lower AHI,
      CT90, CT90%, and MI; higher L-Sao(2); and fewer glucose and lipid metabolism
      abnormalities, shown by lower ApoE and FBG and higher HDL. CONCLUSIONS: Disease
      severity, glucose and lipid metabolism, and Friedman OSA stage may be important
      predictors of surgical outcome of UPPP for OSAHS.

PMID- 21900538
TI  - Nasal tetracaine spray-induced methemoglobinemia.

PMID- 21900534
TI  - Anti-gamma interferon antibodies enhance the immunogenicity of recombinant
      adenovirus vectors.
AB  - Vaccination for eliciting antigen-specific memory CD8(+) T cells may be
      facilitated by manipulating the pleiotropic effects of gamma interferon (IFN
      gamma). We assessed strategies for modulating the contribution of IFN-gamma
      during the development of antigen-specific cytotoxic T lymphocyte (CTL)
      populations. We first showed that recombinant IFN-gamma suppressed antigen
      expression in vitro from a recombinant adenovirus (rAd) vector in a dose
      dependent manner and that addition of an anti-IFN-gamma antibody (Ab) eliminated
      this suppression. Consistent with these in vitro findings, we found that HIV-1
      envelope (Env)-specific CTL responses were higher in IFN-gamma-knockout (GKO)
      mice than in wild-type mice following immunization with rAd. Since these
      observations suggested that IFN-gamma might suppress rAd-induced CTL development,
      we assessed the ability of anti-IFN-gamma Ab administration to augment rAd
      elicited CTL in vivo. In fact, blockage of IFN-gamma activity by monoclonal Ab
      administration was associated with elevated levels of interleukin 7 receptor
      alpha chain-positive (IL-7Ralpha(+)) Env-specific CTL populations postboost.
      These observations illustrate the utility of an anti-IFN-gamma Ab for
      potentiating rAd immunizations to effect quantitative and qualitative changes in
      the effector and memory CTL populations.

PMID- 21900539
TI  - T1-T2 squamous cell carcinoma of the uvula: a little big enemy.
AB  - OBJECTIVE: No specific epidemiology data are available for carcinoma of the
      uvula. This study aims to analyze the epidemiological characteristics and
      treatment outcomes of carcinoma of the uvula at the authors' institution. STUDY
      DESIGN: Case series with chart review. SETTING: Service of ENT-Head and Neck
      Surgery, University Hospital Complex of Santiago de Compostela (CHUS), Spain.
      SUBJECTS AND METHODS: Retrospective epidemiological study of 21 male patients,
      mean age 57.52 years, diagnosed with squamous cell carcinoma of the uvula in the
      CHUS between January 1990 and June 2009. RESULTS: Most patients presented with
      odynophagia and exophytic lesions microscopically consistent with moderately
      differentiated squamous cell carcinoma. Despite the size of the lesions (T1 and
      T2), more than half of the patients had lymph node metastases at diagnosis. More
      than 90.0% of patients with lesions larger than 1 cm presented with lymph node
      metastases. Although more than 70.0% of patients underwent a neck dissection in
      the first year after diagnosis, only 25.0% were free of metastatic disease.
      Recurrences occurred at a mean of 14 months from baseline in more than 50.0% of
      cases. Of the patients, 52.4% died, with a median survival of 38.15 months after
      diagnosis. The overall 5-year survival was 39.0%. According to tumor size, 5-year
      survival was 53.0% for T1 and 27.0% for T2. CONCLUSION: According to the data,
      clinical features of carcinoma of the uvula correspond with aggressive tumors,
      with rapid onset and a major negative impact regardless of tumor size at
      diagnosis. Early stage patients benefit significantly from surgical treatments
      with neck dissections.

PMID- 21900540
TI  - CharlesTaylor, phronesis, and medicine: ethics and interpretation in illness
      narrative.
AB  - This paper provides a brief overview and critique of the dominant objectivist
      understanding and use of illness narrative in Enlightenment (scientific) medicine
      and ethics, as well as several revisionist accounts, which reflect the evolution
      of this approach. In light of certain limitations and difficulties endemic in the
      objectivist understanding of illness narrative, an alternative phronesis approach
      to medical ethics influenced by Charles Taylor's account of the interpretive
      nature of human agency and language is examined. To this end, the account of
      interpretive medical responsibility previously described by Schultz and Carnevale
      as "clinical phronesis" (based upon Taylor's notion of "strong" or "radical
      evaluation") is reviewed and expanded. The thesis of this paper is that illness
      narrative has the ability to benefit patients as well as the potential to cause
      harm or iatrogenic effects. This benefit or harm is contingent upon how the story
      is told and understood. Consequently, these tales are not simply "nice stories,"
      cathartic gestures, or mere supplements to scientific procedures and decision
      making, as suggested by the objectivist approach. Rather, they open the agent to
      meanings that provide a context for explanation and evaluation of illness
      episodes and therapeutic activities. This understanding provides indicators
      (guides) for right action. Hence, medical responsibility as clinical phronesis
      involves, first, the patient and provider's coformulation and cointerpretation of
      what is going on in the patient's illness narrative, and second, the patient and
      provider's response to interpretation of the facts of illness and what they
      signify-not simply a response to the brute facts of illness, alone. The appeal to
      medical responsibility as clinical phronesis thus underscores the importance of
      getting the patient's story of illness right. It is anticipated that further
      elaboration concerning the idea of clinical phronesis as interpretive illness
      narrative will provide a new foundation for medical ethics and decision making.

PMID- 21900541
TI  - Pancreatitis in hyperlipemic mink (Mustela vison).
AB  - In both man and animals, inflammatory changes in the pancreas often occur with
      disturbances in lipid metabolism, including hypertriglyceridemia and an excess of
      free fatty acids. Hyperlipoproteinemia type I is a human condition caused by a
      deficiency of lipoprotein lipase. A similar metabolic disturbance that occurs in
      mink is of considerable comparative interest, as it is also followed by
      pancreatitis. Pancreatic lesions in hyperlipoproteinemic mink included overt
      variably sized nodules with hemorrhage and necrosis. These lesions began as
      intralobular necrosis of exocrine cells and progressed to total lobular
      destruction, with eventual involvement of interlobular tissue. Remnants of
      epithelial cells and lipid-filled macrophages were seen in necrotic areas, along
      with other types of inflammatory cells scattered in a lipid-rich exudate.
      Granulation tissue developed rapidly in necrotic areas. Additional observations
      included ductal proliferation, replacement of epithelial cells with fat, and
      mural arterial thickening, most conspicuously with vacuolated cells and
      endothelial proliferation. Extravasation of lipid-rich plasma is thought to be a
      major intensifier of the inflammatory response.

PMID- 21900542
TI  - Morphologic and molecular analysis of 39 spontaneous feline pulmonary carcinomas.
AB  - The present study was performed to determine the morphologic change and selected
      molecular features of spontaneous lung tumors in cats examined at the North
      Carolina State University Veterinary Teaching Hospital. Thirty-nine primary lung
      carcinomas represented 0.69% of all feline cases admitted to the hospital. Most
      lung tumors were observed in aged cats (P < .0001), and no sex predilection was
      found (P < .4241). Persian cats with pulmonary carcinoma were overrepresented in
      the data set, at least 4 times more frequently than other breeds. The histologic
      tumor types included adenocarcinoma (64.1%), bronchioloalveolar carcinoma
      (20.5%), and adenosquamous carcinoma (15.4%). Metastasis was observed in about
      80% of 39 cases, with decreasing order of intrapulmonary metastasis,
      intrathoracic carcinomatosis, regional lymph nodes, and distant organs, including
      digits. The size of the largest tumor mass was significantly associated with
      metastatic potential (P < .001). Based on immunohistochemistry, more than 80% (20
      of 24) of feline lung tumors were positively labeled with either surfactant
      protein A or thyroid transcription factor 1. Epidermal growth factor receptor
      mutant and p53 proteins were detected in approximately 20% (5 of 24) and 25% (6
      of 24) of the feline lung tumor cases, respectively. Limited sequencing analysis
      of K-ras and p53 genes in 3 selected normal and neoplastic lung tissues did not
      reveal any alteration. Results indicate that primary lung carcinomas are rare but
      aggressive tumors in cats, thereby warranting further studies on molecular
      carcinogenesis.

PMID- 21900543
TI  - Neurolymphomatosis in a dog with B-cell lymphoma.
AB  - Lymphoma in the left femoral nerve of a 10-year-old English Cocker Spaniel caused
      complete paralysis of the affected limb. Neoplastic cells were immunopositive for
      CD79a and Pax5 and negative for CD3. Neoplastic cells were in multiple lymph
      nodes and one kidney but spared bone marrow. The clinical and histologic features
      in this case resemble those of the rare human condition of neurolymphomatosis.

PMID- 21900544
TI  - Somatotroph pituitary tumors in budgerigars (Melopsittacus undulatus).
AB  - A series of 11 pituitary tumors in budgerigars were classified on the basis of
      their clinical, gross, microscopic, and immunohistochemical characteristics.
      Affected birds were young to middle-aged. Clinically, neurologic signs--including
      difficulties flying, ataxia, and blindness--were most commonly reported.
      Additional clinical signs included weight loss, abnormal feathers or molting,
      increased respiratory efforts, and exophthalmos. Nine birds were diagnosed with
      chromophobic pituitary adenomas, and 2 birds had chromophobic pituitary
      carcinomas. Only 1 tumor was delimited to the pituitary gland; the other 10
      variably invaded the brain, skull, and retrobulbar space. Distant metastases were
      identified in 2 birds. All tumors were immunohistochemically strongly positive
      for growth hormone, consistent with the diagnosis of somatotroph tumors. The
      common occurrence and early onset may suggest a genetic predisposition of
      budgerigars to develop somatotroph pituitary tumors with a high incidence of
      local invasion and with metastatic potential.

PMID- 21900545
TI  - Abnormal brain microstructure in patients with chronic pancreatitis.

PMID- 21900548
TI  - Bacterial proteases in IBD and IBS.
AB  - Proteases play a decisive role in health and disease. They fulfil diverse
      functions and have been associated with the pathology of gastrointestinal
      disorders such as inflammatory bowel disease (IBD) and irritable bowel syndrome
      (IBS). The current knowledge focuses on host-derived proteases including matrix
      metalloproteinases, various serine proteases and cathepsins. The possible
      contribution of bacterial proteases has been largely ignored in the pathogenesis
      of IBD and IBS, although there is increasing evidence, especially demonstrated
      for proteases from pathogenic bacteria. The underlying mechanisms extend to
      proteases from commensal bacteria which may be relevant for disease
      susceptibility. The intestinal microbiota and its proteolytic capacity exhibit
      the potential to contribute to the pathogenesis of IBD and IBS. This review
      highlights the relevance of host- and bacteria-derived proteases and their
      signalling mechanisms.

PMID- 21900549
TI  - Does meditation reduce pain through a unique neural mechanism?

PMID- 21900546
TI  - NADPH oxidase complex and IBD candidate gene studies: identification of a rare
      variant in NCF2 that results in reduced binding to RAC2.
AB  - OBJECTIVE: The NOX2 NADPH oxidase complex produces reactive oxygen species and
      plays a critical role in the killing of microbes by phagocytes. Genetic mutations
      in genes encoding components of the complex result in both X-linked and autosomal
      recessive forms of chronic granulomatous disease (CGD). Patients with CGD often
      develop intestinal inflammation that is histologically similar to Crohn's
      colitis, suggesting a common aetiology for both diseases. The aim of this study
      is to determine if polymorphisms in NOX2 NADPH oxidase complex genes that do not
      cause CGD are associated with the development of inflammatory bowel disease
      (IBD). METHODS: Direct sequencing and candidate gene approaches were used to
      identify susceptibility loci in NADPH oxidase complex genes. Functional studies
      were carried out on identified variants. Novel findings were replicated in
      independent cohorts. RESULTS: Sequence analysis identified a novel missense
      variant in the neutrophil cytosolic factor 2 (NCF2) gene that is associated with
      very early onset IBD (VEO-IBD) and subsequently found in 4% of patients with VEO
      IBD compared with 0.2% of controls (p=1.3*10(-5), OR 23.8 (95% CI 3.9 to 142.5);
      Fisher exact test). This variant reduced binding of the NCF2 gene product
      p67(phox) to RAC2. This study found a novel genetic association of RAC2 with
      Crohn's disease (CD) and replicated the previously reported association of NCF4
      with ileal CD. CONCLUSION: These studies suggest that the rare novel p67(phox)
      variant results in partial inhibition of oxidase function and are associated with
      CD in a subgroup of patients with VEO-IBD; and suggest that components of the
      NADPH oxidase complex are associated with CD.

PMID- 21900551
TI  - Acquisition of neural learning in cerebellum and cerebral cortex for smooth
      pursuit eye movements.
AB  - We evaluated the emergence of neural learning in the frontal eye fields
      (FEF(SEM)) and the floccular complex of the cerebellum while monkeys learned a
      precisely timed change in the direction of pursuit eye movement. For each neuron,
      we measured the time course of changes in neural response across a learning
      session that comprised at least 100 repetitions of an instructive change in
      target direction. In both areas, the average population learning curves tracked
      the behavioral changes with high fidelity, consistent with possible roles in
      driving learning. However, the learning curves of individual neurons sometimes
      bore little relation to the smooth, monotonic progression of behavioral learning.
      In the FEF(SEM), neural learning was episodic. For individual neurons, learning
      appeared at different times during the learning session and sometimes disappeared
      by the end of the session. Different FEF(SEM) neurons expressed maximal learning
      at different times relative to the acquisition of behavioral learning. In the
      floccular complex, many Purkinje cells acquired learned simple-spike responses
      according to the same time course as behavioral learning and retained their
      learned responses throughout the learning session. A minority of Purkinje cells
      acquired learned responses late in the learning session, after behavioral
      learning had reached an asymptote. We conclude that learning in single neurons
      can follow a very different time course from behavioral learning. Both the
      FEF(SEM) and the floccular complex contain representations of multiple temporal
      components of learning, with different neurons contributing to learning at
      different times during the acquisition of a learned movement.

PMID- 21900550
TI  - Transsynaptic activity-dependent regulation of axon branching and neurotrophin
      expression in vivo.
AB  - The two major classes of activity-dependent neuroplasticity predict different
      consequences of activity alteration on circuit response. Hebbian plasticity
      (positive feedback) posits that alteration of neuronal activity causes a parallel
      response within a circuit. In contrast, homeostatic plasticity (negative
      feedback) predicts that altering neuronal activity results in compensatory
      responses within a circuit. The relative roles of these modes of plasticity in
      vivo are unclear, since neuronal circuits are difficult to manipulate in the
      intact organism. In this study, we tested the in vivo effects of activity
      deprivation in the superior cervical ganglion-pineal circuit of adult rats, which
      can be noninvasively silenced by exposing animals to constant light. We
      demonstrated that total deprivation of sympathetic activity markedly decreased
      the presence of axonal proteins in the pineal and reduced the density and
      thickness of sympathetic axonal arbors. In addition, we demonstrated that
      sympathetic inactivity eliminated pineal function and markedly decreased pineal
      expression of neurotrophins. Administration of beta-adrenergic agonist restored
      the expression of presynaptic and postsynaptic proteins. Furthermore,
      compensatory axonal growth through collateral sprouting, normally seen following
      unilateral denervation of the pineal, was profoundly impaired in the absence of
      neural activity. Thus, these data suggest that sympathetic axonal terminals are
      maintained by neural activity that induces neurotrophins, which may act through a
      retrograde mechanism to preserve the integrity of axonal arbors via a positive
      feedback loop. Conversely, by using Hebbian-like neuroplasticity, silent yet
      intact circuits enter a hibernation mode marked by reduction of presynaptic
      axonal structures and dramatically reduced postsynaptic expression of
      neurotrophins.

PMID- 21900552
TI  - Group II/III metabotropic glutamate receptors exert endogenous activity-dependent
      modulation of TRPV1 receptors on peripheral nociceptors.
AB  - There is pharmacological evidence that group II and III metabotropic glutamate
      receptors (mGluRs) function as activity-dependent autoreceptors, inhibiting
      transmission in supraspinal sites. These receptors are expressed by peripheral
      nociceptors. We investigated whether mGluRs function as activity-dependent
      autoreceptors inhibiting pain transmission to the rat CNS, particularly transient
      receptor potential vanilloid 1 (TRPV1)-induced activity. Blocking peripheral
      mGluR activity by intraplantar injection of antagonists LY341495 [(2S)-2-amino-2
      [(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid] (LY) (20, 100
      MUm, group II/III), APICA [(RS)-1-amino-5-phosphonoindan-1-carboxylic acid] (100
      MUm, group II), or UBP1112 (alpha-methyl-3-methyl-4-phosphonophenylglycine) (30
      MUm, group III) increased capsaicin (CAP)-induced nociceptive behaviors and
      nociceptor activity. In contrast, group II agonist APDC [(2R,4R)-4
      aminopyrrolidine-2,4-dicarboxylate] (0.1 MUm) or group III agonist l-(+)-2-amino
      4-phosphonobutyric acid (l-AP-4) (10 MUm) blocked the LY-induced increase. Ca(2+)
      imaging in dorsal root ganglion (DRG) cells confirmed LY enhanced CAP-induced
      Ca(2+) mobilization, which was blocked by APDC and l-AP-4. We hypothesized that
      excess glutamate (GLU) released by high intensity and/or prolonged stimulation
      endogenously activated group II/III, dampening nociceptor activation. In support
      of this, intraplantar GLU + LY produced heat hyperalgesia, and exogenous GLU + LY
      applied to nociceptors produced enhanced nociceptor activity and thermal
      sensitization. Intraplantar Formalin, known to elevate extracellular GLU,
      enhanced pain behaviors in the presence of LY. LY alone produced no pain
      behaviors, no change in nociceptor discharge rate or heat-evoked responses, and
      no change in cytosolic Ca(2+) in DRG cells, demonstrating a lack of tonic
      inhibitory control. Group II/III mGluRs maintain an activity-dependent
      autoinhibition, capable of significantly reducing TRPV1-induced activity. They
      are endogenously activated after high-frequency and/or prolonged nociceptor
      stimulation, acting as built-in negative modulators of TRPV1 and nociceptor
      function, reducing pain transmission to the CNS.

PMID- 21900553
TI  - Synaptic properties of thalamic input to the subgranular layers of primary
      somatosensory and auditory cortices in the mouse.
AB  - The classification of synaptic inputs is an essential part of understanding brain
      circuitry. In the present study, we examined the synaptic properties of thalamic
      inputs to pyramidal neurons in layers 5a, 5b, and 6 of primary somatosensory (S1)
      and auditory (A1) cortices in mouse thalamocortical slices. Stimulation of the
      ventral posterior medial nucleus and the ventral division of the medial
      geniculate body resulted in three distinct response classes, two of which have
      never been described before in thalamocortical projections. Class 1A responses
      included synaptic depression and all-or-none responses, while Class 1B responses
      exhibited synaptic depression and graded responses. Class 1C responses are
      characterized by mixed facilitation and depression as well as graded responses.
      Activation of metabotropic glutamate receptors was not observed in any of the
      response classes. We conclude that Class 1 responses can be broken up into three
      distinct subclasses, and that thalamic inputs to the subgranular layers of cortex
      may combine with other, intracortical inputs to drive their postsynaptic target
      cells. We also integrate these results with our recent, analogous study of
      thalamocortical inputs to granular and supragranular layers (Viaene et al.,
      2011).

PMID- 21900554
TI  - Gamma-band activation predicts both associative memory and cortical plasticity.
AB  - Gamma-band oscillations are a ubiquitous phenomenon in the nervous system and
      have been implicated in multiple aspects of cognition. In particular, the
      strength of gamma oscillations at the time a stimulus is encoded predicts its
      subsequent retrieval, suggesting that gamma may reflect enhanced mnemonic
      processing. Likewise, activity in the gamma-band can modulate plasticity in
      vitro. However, it is unclear whether experience-dependent plasticity in vivo is
      also related to gamma-band activation. The aim of the present study was to
      determine whether gamma activation in primary auditory cortex modulates both the
      associative memory for an auditory stimulus during classical conditioning and its
      accompanying specific receptive field plasticity. Rats received multiple daily
      sessions of single tone/shock trace and two-tone discrimination conditioning,
      during which local field potentials and multiunit discharges were recorded from
      chronically implanted electrodes. We found that the strength of tone-induced
      gamma predicted the acquisition of associative memory 24 h later and ceased to
      predict subsequent performance once asymptote was reached. Gamma activation also
      predicted receptive field plasticity that specifically enhanced representation of
      the signal tone. This concordance provides a long-sought link between gamma
      oscillations, cortical plasticity, and the formation of new memories.

PMID- 21900555
TI  - Calcineurin and its regulator sra/DSCR1 are essential for sleep in Drosophila.
AB  - Sleep is a fundamental biological process for all animals. However, the molecular
      mechanisms that regulate sleep are still poorly understood. Here we report that
      sleep-like behavior in Drosophila is severely impaired by mutations in sarah
      (sra), a member of the Regulator of Calcineurin (RCAN) family of genes. Sleep
      reduction in sra mutants is highly correlated with decreases in Sra protein
      levels. Pan-neural expression of sra rescues this behavioral phenotype,
      indicating that neuronal sra function is required for normal sleep. Since Sra
      regulates calcineurin (CN), we generated and examined the behavior of knock-out
      mutants for all Drosophila CN genes: CanA-14F, Pp2B-14D, and CanA1 (catalytic
      subunits), and CanB and CanB2 (regulatory subunits). While all mutants show at
      least minor changes in sleep, CanA-14F(KO) and CanB(KO) have striking reductions,
      suggesting that these are the major CN subunits regulating sleep. In addition,
      neuronal expression of constitutively active forms of CN catalytic subunits also
      significantly reduces sleep, demonstrating that both increases and decreases in
      CN activity inhibit sleep. sra sleep defects are suppressed by CN mutations,
      indicating that sra and CN affect sleep through a common mechanism. Our results
      demonstrate that CN and its regulation by Sra are required for normal sleep in
      Drosophila and identify a critical role of Ca(2+)/calmodulin-dependent signaling
      in sleep regulation.

PMID- 21900556
TI  - Dynamics of population response to changes of motion direction in primary visual
      cortex.
AB  - The visual system is thought to represent the direction of moving objects in the
      relative activity of large populations of cortical neurons that are broadly tuned
      to the direction of stimulus motion, but how changes in the direction of a moving
      stimulus are represented in the population response remains poorly understood.
      Here we take advantage of the orderly mapping of direction selectivity in ferret
      primary visual cortex (V1) to explore how abrupt changes in the direction of a
      moving stimulus are encoded in population activity using voltage-sensitive dye
      imaging. For stimuli moving in a constant direction, the peak of the V1
      population response accurately represented the direction of stimulus motion, but
      following abrupt changes in motion direction, the peak transiently departed from
      the direction of stimulus motion in a fashion that varied with the direction
      offset angle and was well predicted from the response to the component
      directions. We conclude that cortical dynamics and population coding mechanisms
      combine to place constraints on the accuracy with which abrupt changes in
      direction of motion can be represented by cortical circuits.

PMID- 21900557
TI  - Abnormalities in the climbing fiber-Purkinje cell circuitry contribute to
      neuronal dysfunction in ATXN1[82Q] mice.
AB  - One fundamental unanswered question in the field of polyglutamine diseases
      concerns the pathophysiology of neuronal dysfunction. Is there dysfunction in a
      specific neuronal population or circuit initially that contributes the onset of
      behavioral abnormalities? This study used a systems-level approach to investigate
      the functional integrity of the excitatory cerebellar cortical circuitry in vivo
      from several transgenic ATXN1 mouse lines. We tested the hypotheses that there
      are functional climbing fiber (CF)-Purkinje cell (PC) and parallel fiber (PF)-PC
      circuit abnormalities using flavoprotein autofluorescence optical imaging and
      extracellular field potential recordings. In early-symptomatic and symptomatic
      animals expressing ATXN1[82Q], there is a marked reduction in PC responsiveness
      to CF activation. Immunostaining of vesicular glutamate transporter type 2
      demonstrated a decrement in CF extension on PC dendrites in symptomatic
      ATXN1[82Q] mice. In contrast, responses to PF stimulation were relatively normal.
      Importantly, the deficits in CF-PC synaptic transmission required expression of
      pathogenic ataxin-1 (ATXN1[82Q]) and for its entrance into the nucleus of PCs.
      Loss of endogenous mouse Atxn1 had no discernible effects. Furthermore, the
      abnormalities in CF-PC synaptic transmission were ameliorated when mutant
      transgene expression was prevented during postnatal cerebellar development. The
      results demonstrate the preferential susceptibility of the CF-PC circuit to the
      effects of ATXN1[82Q]. Further, this deficit likely contributes to the abnormal
      motor phenotype of ATXN1[82Q] mice. For polyglutamine diseases generally, the
      findings support a model whereby specific neuronal circuits suffer insults that
      alter function before cell death.

PMID- 21900558
TI  - Selective hippocampal neurodegeneration in transgenic mice expressing small
      amounts of truncated Abeta is induced by pyroglutamate-Abeta formation.
AB  - Posttranslational amyloid-beta (Abeta) modification is considered to play an
      important role in Alzheimer's disease (AD) etiology. An N-terminally modified
      Abeta species, pyroglutamate-amyloid-beta (pE3-Abeta), has been described as a
      major constituent of Abeta deposits specific to human AD but absent in normal
      aging. Formed via cyclization of truncated Abeta species by glutaminyl cyclase
      (QC; QPCT) and/or its isoenzyme (isoQC; QPCTL), pE3-Abeta aggregates rapidly and
      is known to seed additional Abeta aggregation. To directly investigate pE3-Abeta
      toxicity in vivo, we generated and characterized transgenic TBA2.1 and TBA2.2
      mice, which express truncated mutant human Abeta. Along with a rapidly developing
      behavioral phenotype, these mice showed progressively accumulating Abeta and pE3
      Abeta deposits in brain regions of neuronal loss, impaired long-term
      potentiation, microglial activation, and astrocytosis. Illustrating a threshold
      for pE3-Abeta neurotoxicity, this phenotype was not found in heterozygous animals
      but in homozygous TBA2.1 or double-heterozygous TBA2.1/2.2 animals only. A
      significant amount of pE3-Abeta formation was shown to be QC-dependent, because
      crossbreeding of TBA2.1 with QC knock-out, but not isoQC knock-out, mice
      significantly reduced pE3-Abeta levels. Hence, lowering the rate of QC-dependent
      posttranslational pE3-Abeta formation can, in turn, lower the amount of
      neurotoxic Abeta species in AD.

PMID- 21900559
TI  - Pitx3 is a critical mediator of GDNF-induced BDNF expression in nigrostriatal
      dopaminergic neurons.
AB  - Pitx3 is a critical homeodomain transcription factor for the proper development
      and survival of mesodiencephalic dopaminergic (mdDA) neurons in mammals. Several
      variants of this gene have been associated with human Parkinson's disease (PD),
      and lack of Pitx3 in mice causes the preferential loss of substantia nigra pars
      compacta (SNc) mdDA neurons that are most affected in PD. It is currently unclear
      how Pitx3 activity promotes the survival of SNc mdDA neurons and which factors
      act upstream and downstream of Pitx3 in this context. Here we show that a
      transient expression of glial cell line-derived neurotrophic factor (GDNF) in the
      murine ventral midbrain (VM) induces transcription of Pitx3 via NF-kappaB
      mediated signaling, and that Pitx3 is in turn required for activating the
      expression of brain-derived neurotrophic factor (BDNF) in a rostrolateral (SNc)
      mdDA neuron subpopulation during embryogenesis. The loss of BDNF expression
      correlates with the increased apoptotic cell death of this mdDA neuronal
      subpopulation in Pitx3(-/-) mice, whereas treatment of VM cell cultures with BDNF
      augments the survival of the Pitx3(-/-) mdDA neurons. Most importantly, only BDNF
      but not GDNF protects mdDA neurons against 6-hydroxydopamine-induced cell death
      in the absence of Pitx3. As the feedforward regulation of GDNF, Pitx3, and BDNF
      expression also persists in the adult rodent brain, our data suggest that the
      disruption of the regulatory interaction between these three factors contributes
      to the loss of mdDA neurons in Pitx3(-/-) mutant mice and perhaps also in human
      PD.

PMID- 21900560
TI  - Contextual novelty modulates the neural dynamics of reward anticipation.
AB  - We investigated how rapidly the reward-predicting properties of visual cues are
      signaled in the human brain and the extent these reward prediction signals are
      contextually modifiable. In a magnetoencephalography study, we presented
      participants with fractal visual cues that predicted monetary rewards with
      different probabilities. These cues were presented in the temporal context of a
      preceding novel or familiar image of a natural scene. Starting at ~100 ms after
      cue onset, reward probability was signaled in the event-related fields (ERFs)
      over temporo-occipital sensors and in the power of theta (5-8 Hz) and beta (20-30
      Hz) band oscillations over frontal sensors. While theta decreased with reward
      probability beta power showed the opposite effect. Thus, in humans anticipatory
      reward responses are generated rapidly, within 100 ms after the onset of reward
      predicting cues, which is similar to the timing established in non-human
      primates. Contextual novelty enhanced the reward anticipation responses in both
      ERFs and in beta oscillations starting at ~100 ms after cue onset. This very
      early context effect is compatible with a physiological model that invokes the
      mediation of a hippocampal-VTA loop according to which novelty modulates neural
      response properties within the reward circuitry. We conclude that the neural
      processing of cues that predict future rewards is temporally highly efficient and
      contextually modifiable.

PMID- 21900561
TI  - Spinal 5-HT(3) receptor activation induces behavioral hypersensitivity via a
      neuronal-glial-neuronal signaling cascade.
AB  - Recent studies indicate that the descending serotonin (5-HT) system from the
      rostral ventromedial medulla (RVM) in the brainstem and the 5-HT(3) receptor
      subtype in the spinal dorsal horn are involved in enhanced descending pain
      facilitation after tissue and nerve injury. However, the mechanisms underlying
      the activation of the 5-HT(3) receptor and its contribution to facilitation of
      pain remain unclear. In the present study, activation of spinal 5-HT(3) receptor
      by intrathecal injection of a selective 5-HT(3) receptor agonist, SR57227,
      induced spinal glial hyperactivity, neuronal hyperexcitability, and pain
      hypersensitivity in rats. We found that there was neuron-to-microglia signaling
      via chemokine fractalkine, microglia to astrocyte signaling via the cytokine IL
      18, astrocyte to neuronal signaling by IL-1beta, and enhanced activation of GluN
      (NMDA) receptors in the spinal dorsal horn. In addition, exogenous brain-derived
      neurotrophic factor-induced descending pain facilitation was accompanied by
      upregulation of CD11b and GFAP expression in the spinal dorsal horn after
      microinjection in the RVM, and these events were significantly prevented by
      functional blockade of spinal 5-HT(3) receptors. Enhanced expression of spinal
      CD11b and GFAP after hindpaw inflammation was also attenuated by molecular
      depletion of the descending 5-HT system by intra-RVM Tph-2 shRNA interference.
      Thus, these findings offer new insights into the cellular and molecular
      mechanisms at the spinal level responsible for descending 5-HT-mediated pain
      facilitation during the development of persistent pain after tissue and nerve
      injury. New pain therapies should focus on prime targets of descending
      facilitation-induced glial involvement, and in particular the blocking of
      intercellular signaling transduction between neuron and glia.

PMID- 21900562
TI  - Depth-dependent temporal response properties in core auditory cortex.
AB  - The computational role of cortical layers within auditory cortex has proven
      difficult to establish. One hypothesis is that interlaminar cortical processing
      might be dedicated to analyzing temporal properties of sounds; if so, then there
      should be systematic depth-dependent changes in cortical sensitivity to the
      temporal context in which a stimulus occurs. We recorded neural responses
      simultaneously across cortical depth in primary auditory cortex and anterior
      auditory field of CBA/Ca mice, and found systematic depth dependencies in
      responses to second-and-later noise bursts in slow (1-10 bursts/s) trains of
      noise bursts. At all depths, responses to noise bursts within a train usually
      decreased with increasing train rate; however, the rolloff with increasing train
      rate occurred at faster rates in more superficial layers. Moreover, in some
      recordings from mid-to-superficial layers, responses to noise bursts within a 3-4
      bursts/s train were stronger than responses to noise bursts in slower trains.
      This non-monotonicity with train rate was especially pronounced in more
      superficial layers of the anterior auditory field, where responses to noise
      bursts within the context of a slow train were sometimes even stronger than
      responses to the noise burst at train onset. These findings may reflect depth
      dependence in suppression and recovery of cortical activity following a stimulus,
      which we suggest could arise from laminar differences in synaptic depression at
      feedforward and recurrent synapses.

PMID- 21900563
TI  - The neural and cognitive time course of theory of mind.
AB  - Neuroimaging and neuropsychological studies implicate both frontal and
      temporoparietal cortices when humans reason about the mental states of others.
      Here, we report an event-related potentials study of the time course of one such
      "theory of mind" ability: visual perspective taking. The findings suggest that
      posterior cortex, perhaps the temporoparietal cortex, calculates and represents
      the perspective of self versus other, and then, later, the right frontal cortex
      resolves conflict between perspectives during response selection.

PMID- 21900564
TI  - Variability of the relationship between electrophysiology and BOLD-fMRI across
      cortical regions in humans.
AB  - The relationship between blood oxygenation level-dependent (BOLD) functional MRI
      (fMRI) signal and the underlying neural electrical activity in humans is a topic
      of intense interest to systems neuroscience. This relationship has generally been
      assumed to be invariant regardless of the brain region and the cognitive task
      being studied. We critically evaluated these assumptions by comparing the BOLD
      fMRI response with local field potential (LFP) measurements during visually cued
      common noun and verb generation in 11 humans in whom 1210 subdural electrodes
      were implanted. As expected, power in the mid-gamma band (60-120 Hz) correlated
      positively (r(2) = 0.16, p < 10(-16)) and power in the beta band (13-30 Hz)
      correlated negatively (r(2) = 0.09, p < 10(-16)) with the BOLD signal change.
      Beta and mid-gamma band activity independently explain different components of
      the observed BOLD signal. Importantly, we found that the location (i.e., lobe) of
      the recording site modulates the relationship between the electrocorticographic
      (ECoG) signal and the observed fMRI response (p < 10(-16), F(21,1830) = 52.7),
      while the type of language task does not. Across all brain regions, ECoG activity
      in the gamma and beta bands explains 22% of the fMRI response, but if the lobar
      location is considered, 28% of the variance can be explained. Further evaluation
      of this relationship at the level of individual gyri provides additional evidence
      of differences in the BOLD-LFP relationship by cortical locus. This spatial
      variability in the relationship between the fMRI signal and neural activity
      carries implications for modeling of the hemodynamic response function, an
      essential step for interregional fMRI comparisons.

PMID- 21900565
TI  - Nucleus accumbens dopamine/glutamate interaction switches modes to generate
      desire versus dread: D(1) alone for appetitive eating but D(1) and D(2) together
      for fear.
AB  - The medial shell of nucleus accumbens (NAc) and its mesolimbic dopamine inputs
      mediate forms of fearful as well as of incentive motivation. For example, either
      appetitive and/or actively fearful behaviors are generated in a keyboard pattern
      by localized glutamate disruptions in NAc (via microinjection of the AMPA
      receptor antagonist DNQX) at different anatomical locations along a rostrocaudal
      gradient within the medial shell of rats. Rostral glutamate disruptions produce
      intense increases in eating, but more caudally placed disruptions produce
      increasingly fearful behaviors: distress vocalizations and escape attempts to
      human touch, and a spontaneous and directed antipredator response called
      defensive treading/burying. Local endogenous dopamine is required for either
      intense motivation to be generated by AMPA disruptions. Here we report that only
      endogenous local signaling at D(1) dopamine receptors is needed for rostral
      generation of excessive eating, potentially implicating a direct output pathway
      contribution. In contrast, fear generation at caudal sites requires both D(1) and
      D(2) signaling simultaneously, potentially implicating an indirect output pathway
      contribution. Finally, when motivation valence generated by AMPA disruptions at
      intermediate sites was flipped by manipulating environmental ambience, from
      mostly appetitive in a comfortable home environment to mostly fearful in a
      stressful environment, the roles of local D(1) and D(2) signaling in
      dopamine/glutamate interaction at microinjection sites also switched dynamically
      to match the motivation valence generated at the moment. Thus, NAc D(1) and D(2)
      receptors, and their associated neuronal circuits, play different and dynamic
      roles in enabling desire and dread to be generated by localized NAc glutamate
      disruptions in medial shell.

PMID- 21900566
TI  - Breathing without CO(2) chemosensitivity in conditional Phox2b mutants.
AB  - Breathing is a spontaneous, rhythmic motor behavior critical for maintaining
      O(2), CO(2), and pH homeostasis. In mammals, it is generated by a neuronal
      network in the lower brainstem, the respiratory rhythm generator (Feldman et al.,
      2003). A century-old tenet in respiratory physiology posits that the respiratory
      chemoreflex, the stimulation of breathing by an increase in partial pressure of
      CO(2) in the blood, is indispensable for rhythmic breathing. Here we have
      revisited this postulate with the help of mouse genetics. We have engineered a
      conditional mouse mutant in which the toxic PHOX2B(27Ala) mutation that causes
      congenital central hypoventilation syndrome in man is targeted to the
      retrotrapezoid nucleus, a site essential for central chemosensitivity. The
      mutants lack a retrotrapezoid nucleus and their breathing is not stimulated by
      elevated CO(2) at least up to postnatal day 9 and they barely respond as
      juveniles, but nevertheless survive, breathe normally beyond the first days after
      birth, and maintain blood PCO(2) within the normal range. Input from peripheral
      chemoreceptors that sense PO(2) in the blood appears to compensate for the
      missing CO(2) response since silencing them by high O(2) abolishes rhythmic
      breathing. CO(2) chemosensitivity partially recovered in adulthood. Hence, during
      the early life of rodents, the excitatory input normally afforded by elevated
      CO(2) is dispensable for life-sustaining breathing and maintaining CO(2)
      homeostasis in the blood.

PMID- 21900567
TI  - Vulnerability to depression: from brain neuroplasticity to identification of
      biomarkers.
AB  - A stressful event increases the risk of developing depression later in life, but
      the possible predisposing factors remain unknown. Our study aims to characterize
      latent vulnerability traits underlying the development of depressive disorders in
      adult animals. Four weeks after a priming stressful event, serum corticosterone
      concentration returned to control values in all animals, whereas the other
      biological parameters returned to basal level in only 58% of animals (called
      nonvulnerable). In contrast, 42% of animals displayed persistent decreased serum
      and hippocampus BDNF concentrations, reduced hippocampal volume and neurogenesis,
      CA3 dendritic retraction and decrease in spine density, as well as amygdala
      neuron hypertrophy, constituting latent vulnerability traits to depression. In
      this group, called vulnerable, a subsequent mild stress evoked a rise of serum
      corticosterone levels and a "depressive" phenotype, in contrast to nonvulnerable
      animals. Intracerebroventricular administration of 7,8-dihydroxyflavone, a
      selective TrkB receptor agonist, dampened the development of the "depressive"
      phenotype. Our results thus characterize the presence of latent vulnerability
      traits that underlie the emergence of depression and identify the association of
      low BDNF with normal corticosterone serum concentrations as a predictive
      biomarker of vulnerability to depression.

PMID- 21900568
TI  - Attentional modulation of fMRI responses in human V1 is consistent with distinct
      spatial maps for chromatically defined orientation and contrast.
AB  - Attending to different stimulus features such as contrast or orientation can
      change the pattern of neural responses in human V1 measured with fMRI. We show
      that these pattern changes are much more distinct for colored stimuli than for
      achromatic stimuli. This is evidence for a classic model of V1 functional
      architecture in which chromatic contrast and orientation are coded in spatially
      distinct neural domains, while achromatic contrast and orientation are not.

PMID- 21900569
TI  - Direct structural connections between voice- and face-recognition areas.
AB  - Currently, there are two opposing models for how voice and face information is
      integrated in the human brain to recognize person identity. The conventional
      model assumes that voice and face information is only combined at a supramodal
      stage (Bruce and Young, 1986; Burton et al., 1990; Ellis et al., 1997). An
      alternative model posits that areas encoding voice and face information also
      interact directly and that this direct interaction is behaviorally relevant for
      optimizing person recognition (von Kriegstein et al., 2005; von Kriegstein and
      Giraud, 2006). To disambiguate between the two different models, we tested for
      evidence of direct structural connections between voice- and face-processing
      cortical areas by combining functional and diffusion magnetic resonance imaging.
      We localized, at the individual subject level, three voice-sensitive areas in
      anterior, middle, and posterior superior temporal sulcus (STS) and face-sensitive
      areas in the fusiform gyrus [fusiform face area (FFA)]. Using probabilistic
      tractography, we show evidence that the FFA is structurally connected with voice
      sensitive areas in STS. In particular, our results suggest that the FFA is more
      strongly connected to middle and anterior than to posterior areas of the voice
      sensitive STS. This specific structural connectivity pattern indicates that
      direct links between face- and voice-recognition areas could be used to optimize
      human person recognition.

PMID- 21900572
TI  - Differential BOLD activity associated with subjective and objective reports
      during "blindsight" in normal observers.
AB  - The study of conscious visual perception invariably necessitates some means of
      report. Report can be either subjective, i.e., an introspective evaluation of
      conscious experience, or objective, i.e., a forced-choice discrimination
      regarding different stimulus states. However, the link between report type and
      fMRI-BOLD signals has remained unknown. Here we used continuous flash suppression
      to render target images invisible, and observed a long-lasting dissociation
      between subjective report of visibility and human subjects' forced-choice
      localization of targets ("blindsight"). Our results show a robust dissociation
      between brain regions and type of report. We find subjective visibility effects
      in high-order visual areas even under equal objective performance. No significant
      BOLD difference was found between correct and incorrect trials in these areas
      when subjective report was constant. On the other hand, objective performance was
      linked to the accuracy of multivariate pattern classification mainly in early
      visual areas. Together, our data support the notion that subjective and objective
      reports tap cortical signals of different location and amplitude within the
      visual cortex.

PMID- 21900570
TI  - Upregulation of KCC2 activity by zinc-mediated neurotransmission via the
      mZnR/GPR39 receptor.
AB  - Vesicular Zn(2+) regulates postsynaptic neuronal excitability upon its corelease
      with glutamate. We previously demonstrated that synaptic Zn(2+) acts via a
      distinct metabotropic zinc-sensing receptor (mZnR) in neurons to trigger Ca(2+)
      responses in the hippocampus. Here, we show that physiological activation of mZnR
      signaling induces enhanced K(+)/Cl(-) cotransporter 2 (KCC2) activity and surface
      expression. As KCC2 is the major Cl(-) outward transporter in neurons, Zn(2+)
      also triggers a pronounced hyperpolarizing shift in the GABA(A) reversal
      potential. Mossy fiber stimulation-dependent upregulation of KCC2 activity is
      eliminated in slices from Zn(2+) transporter 3-deficient animals, which lack
      synaptic Zn(2+). Importantly, activity-dependent ZnR signaling and subsequent
      enhancement of KCC2 activity are also absent in slices from mice lacking the G
      protein-coupled receptor GPR39, identifying this protein as the functional
      neuronal mZnR. Our work elucidates a fundamentally important role for
      synaptically released Zn(2+) acting as a neurotransmitter signal via activation
      of a mZnR to increase Cl(-) transport, thereby enhancing inhibitory tone in
      postsynaptic cells.

PMID- 21900571
TI  - Fukutin-related protein alters the deposition of laminin in the eye and brain.
AB  - Mutations in fukutin-related protein (FKRP) are responsible for a common group of
      muscular dystrophies ranging from adult onset limb girdle muscular dystrophies to
      severe congenital forms with associated structural brain involvement. The
      defining feature of this group of disorders is the hypoglycosylation of alpha
      dystroglycan and its inability to effectively bind extracellular matrix ligands
      such as laminin alpha2. However, alpha-dystroglycan has the potential to interact
      with a number of laminin isoforms many of which are basement membrane/tissue
      specific and developmentally regulated. To further investigate this we evaluated
      laminin alpha-chain expression in the cerebral cortex and eye of our FKRP knock
      down mouse (FKRP(KD)). These mice showed a marked disturbance in the deposition
      of laminin alpha-chains including alpha1, alpha2, alpha4, and alpha5, although
      only laminin alpha1- and gamma1-chain mRNA expression was significantly
      upregulated relative to controls. Moreover, there was a diffuse pattern of
      laminin deposition below the pial surface which correlated with an abrupt
      termination of many of the radial glial cells. This along with the pial basement
      membrane defects, contributed to the abnormal positioning of both early- and late
      born neurons. Defects in the inner limiting membrane of the eye were associated
      with a reduction of laminin alpha1 demonstrating the involvement of the alpha
      dystroglycan:laminin alpha1 axis in the disease process. These observations
      demonstrate for the first time that a reduction in Fkrp influences the ability of
      tissue-specific forms of alpha-dystroglycan to direct the deposition of several
      laminin isoforms in the formation of different basement membranes.

PMID- 21900573
TI  - Carbon nanotube scaffolds tune synaptic strength in cultured neural circuits:
      novel frontiers in nanomaterial-tissue interactions.
AB  - A long-term goal of tissue engineering is to exploit the ability of supporting
      materials to govern cell-specific behaviors. Instructive scaffolds code such
      information by modulating (via their physical and chemical features) the
      interface between cells and materials at the nanoscale. In modern neuroscience,
      therapeutic regenerative strategies (i.e., brain repair after damage) aim to
      guide and enhance the intrinsic capacity of the brain to reorganize by promoting
      plasticity mechanisms in a controlled fashion. Direct and specific interactions
      between synthetic materials and biological cell membranes may play a central role
      in this process. Here, we investigate the role of the material's properties
      alone, in carbon nanotube scaffolds, in constructing the functional building
      blocks of neural circuits: the synapses. Using electrophysiological recordings
      and rat cultured neural networks, we describe the ability of a nanoscaled
      material to promote the formation of synaptic contacts and to modulate their
      plasticity.

PMID- 21900575
TI  - Matrix metalloproteinase-9 contributes to kindled seizure development in
      pentylenetetrazole-treated mice by converting pro-BDNF to mature BDNF in the
      hippocampus.
AB  - Recurrent seizure activity has been shown to induce a variety of permanent
      structural changes in the brain. Matrix metalloproteinases (MMPs) function to
      promote neuronal plasticity, primarily through cleavage of extracellular matrix
      proteins. Here, we investigated the role of MMP-9 in the development of
      pentylenetetrazole (PTZ)-induced kindled seizure in mice. Repeated treatment with
      PTZ (40 mg/kg) produced kindled seizure, which was accompanied by enhanced MMP-9
      activity and expression in the hippocampus. No change in MMP-9 activity was
      observed in the hippocampi of mice with generalized tonic seizure following
      single administration of PTZ (60 mg/kg). MMP-9 colocalized with the neuronal
      marker NeuN and the glial marker GFAP in the dentate gyrus of the kindled mouse
      hippocampus. Coadministration of diazepam or MK-801 with PTZ inhibited the
      development of kindling and the increased MMP-9 levels in the hippocampus. Marked
      suppression of kindled seizure progression in response to repeated PTZ treatment
      was observed in MMP-9((-/-)) mice compared with wild-type mice, an observation
      that was accompanied by decreased hippocampal levels of mature brain-derived
      neurotrophic factor. Microinjecting the BDNF scavenger TrkB-Fc into the right
      ventricle before each PTZ treatment significantly suppressed the development of
      kindling in wild-type mice, whereas no effect was observed in MMP-9((-/-)) mice.
      On the other hand, bilateral injections of pro-BDNF into the hippocampal dentate
      gyrus significantly enhanced kindling in wild-type mice but not MMP-9((-/-))
      mice. These findings suggest that MMP-9 is involved in the progression of
      behavioral phenotypes in kindled mice because of conversion of pro-BDNF to mature
      BDNF in the hippocampus.

PMID- 21900574
TI  - Default mode of brain function in monkeys.
AB  - Human neuroimaging has revealed a specific network of brain regions-the default
      mode network (DMN)-that reduces its activity during goal-directed behavior. So
      far, evidence for a similar network in monkeys is mainly indirect, since, except
      for one positron emission tomography study, it is all based on functional
      connectivity analysis rather than activity increases during passive task states.
      Here, we tested whether a consistent DMN exists in monkeys using its defining
      property. We performed a meta-analysis of functional magnetic resonance imaging
      data collected in 10 awake monkeys to reveal areas in which activity consistently
      decreases when task demands shift from passive tasks to externally oriented
      processing. We observed task-related spatially specific deactivations across 15
      experiments, implying in the monkey a functional equivalent of the human DMN. We
      revealed by resting-state connectivity that prefrontal and medial parietal
      regions, including areas 9/46d and 31, respectively, constitute the DMN core,
      being functionally connected to all other DMN areas. We also detected two
      distinct subsystems composed of DMN areas with stronger functional connections
      between each other. These clusters included areas 24/32, 8b, and TPOC and areas
      23, v23, and PGm, respectively. Such a pattern of functional connectivity largely
      fits, but is not completely consistent with anatomical tract tracing data in
      monkeys. Also, analysis of afferent and efferent connections between DMN areas
      suggests a multisynaptic network structure. Like humans, monkeys increase
      activity during passive epochs in heteromodal and limbic association regions,
      suggesting that they also default to internal modes of processing when not
      actively interacting with the environment.

PMID- 21900576
TI  - Global functional connectivity deficits in schizophrenia depend on behavioral
      state.
AB  - Schizophrenia is a devastating psychiatric illness characterized by deterioration
      of cognitive and emotional processing. It has been hypothesized that aberrant
      cortical connectivity is implicated in the disease (Friston, 1998), yet previous
      studies of functional connectivity (FC) in schizophrenia have shown mixed results
      (Garrity et al., 2007; Jafri et al., 2008; Lynall et al., 2010). We measured FC
      using fMRI in human schizophrenia patients and healthy controls during two
      different tasks and a rest condition, and constructed a voxel-based global FC
      index. We found a striking FC decrease in patients compared with controls. In the
      task conditions, relatively weaker FC was specific to regions of cortex not
      active during the task. In the rest condition, the FC difference between patients
      and controls was larger and allowed a case-by-case separation between individuals
      of the two groups. The results suggest that the relative reduction of FC in
      schizophrenia is dependent on the state of cortical activity, with voxels not
      activated by the task showing higher levels of FC deficiency. This novel finding
      may shed light on previous reports of FC in schizophrenia. Whether this neural
      characteristic is related to the development of the disorder remains to be
      established.

PMID- 21900577
TI  - Mitochondrial Ca(2+) uptake is essential for synaptic plasticity in pain.
AB  - The increase of cytosolic free Ca(2+) ([Ca(2+)](c)) due to NMDA receptor
      activation is a key step for spinal cord synaptic plasticity by altering cellular
      signal transduction pathways. We focus on this plasticity as a cause of
      persistent pain. To provide a mechanism for these classic findings, we report
      that [Ca(2+)](c) does not trigger synaptic plasticity directly but must first
      enter into mitochondria. Interfering with mitochondrial Ca(2+) uptake during a
      [Ca(2+)](c) increase blocks induction of behavioral hyperalgesia and accompanying
      downstream cell signaling, with reduction of spinal long-term potentiation (LTP).
      Furthermore, reducing the accompanying mitochondrial superoxide levels lessens
      hyperalgesia and LTP induction. These results indicate that [Ca(2+)](c) requires
      downstream mitochondrial Ca(2+) uptake with consequent production of reactive
      oxygen species (ROS) for synaptic plasticity underlying chronic pain. These
      results suggest modifying mitochondrial Ca(2+) uptake and thus ROS as a type of
      chronic pain therapy that should also have broader biologic significance.

PMID- 21900578
TI  - Microglial cells contribute to endogenous brain defenses after acute neonatal
      focal stroke.
AB  - Macrophages are viewed as amplifiers of ischemic brain injury, but the origin of
      injury-producing macrophages is poorly defined. The role of resident brain
      macrophages-microglial cells-in stroke remains controversial. To determine
      whether microglial cells exert injurious effects after neonatal focal stroke, we
      selectively depleted these cells with intracerebral injection of liposome
      encapsulated clodronate before transient middle cerebral artery occlusion in
      postnatal day 7 rats. Phagocytosis of apoptotic neurons by activated microglia
      was poor in animals with unmanipulated microglia, and depletion of these cells
      did not increase the number of apoptotic neurons. Lack of microglia increased the
      brain levels of several cytokines and chemokines already elevated by ischemia
      reperfusion, and also increased the severity and volume of injury, suggesting
      that microglial cells contribute to endogenous protection during the subacute
      injury phase. Then, to determine whether accumulation of reactive oxygen species
      in microglia adversely affects phagocytosis of dying neurons and contributes to
      injury, we delivered reduced glutathione (GSH) into microglia, again using
      liposomes. Remarkably, pharmacologically increased intracellular GSH
      concentrations in microglia induced superoxide accumulation in lipid rafts in
      these cells, further increased the brain levels of macrophage chemoattractants,
      and exacerbated injury. Together, these data show that microglia are part of the
      endogenous defense mechanisms and that, while antioxidants can protect the
      injured neonatal brain, high levels of reducing equivalents in activated
      microglia, GSH, trigger superoxide production, favor the reorganization of
      lipids, amplify local inflammation and exacerbate injury.

PMID- 21900580
TI  - A Ca(2+) threshold for induction of spike-timing-dependent depression in the
      mouse striatum.
AB  - The striatum is the principal input nucleus of the basal ganglia, receiving
      glutamatergic afferents from the cerebral cortex. There is much interest in
      mechanisms of synaptic plasticity in the corticostriatal synapses. We used two
      photon microscopy and whole-cell recording to measure changes in intracellular
      calcium concentration ([Ca(2+)](i)) associated with spike-time-dependent
      plasticity in mouse striatum. Uncaging glutamate adjacent to a dendritic spine
      caused a postsynaptic potential at the soma and a rise in spine [Ca(2+)](i).
      Action potentials elicited at the soma raised both dendrite and spine
      [Ca(2+)](i). Pairing protocols in which glutamate uncaging preceded action
      potentials by 10 ms (pre-post protocol) produced supralinear increases in spine
      [Ca(2+)](i) compared with the sum of increases seen with uncaging and action
      potentials alone, or timing protocols in which the uncaging followed the action
      potentials (post-pre protocols). The supralinear component of the increases in
      [Ca(2+)](i) were eliminated by the voltage-sensitive calcium channel blocker
      nimodipine. In the adjacent parent dendrites, the increases in [Ca(2+)](i) were
      neither supralinear nor sensitive to the relative pre-post timing. In parallel
      experiments, we investigated the effects of these pairing protocols on spike
      timing-dependent synaptic plasticity. Long-term depression (t-LTD) of
      corticostriatal inputs was induced by pre-post but not post-pre protocols.
      Intracellular calcium chelators and calcium antagonists blocked pre-post t-LTD,
      confirming that elevated calcium entering via voltage-sensitive calcium channels
      is necessary for t-LTD. These findings confirm a spine [Ca(2+)](i) threshold for
      induction of t-LTD in the corticostriatal pathway, mediated by the supralinear
      increase in [Ca(2+)](i) associated with pre-post induction protocols.

PMID- 21900579
TI  - Early changes in cerebellar physiology accompany motor dysfunction in the
      polyglutamine disease spinocerebellar ataxia type 3.
AB  - The relationship between cerebellar dysfunction, motor symptoms, and neuronal
      loss in the inherited ataxias, including the polyglutamine disease
      spinocerebellar ataxia type 3 (SCA3), remains poorly understood. We demonstrate
      that before neurodegeneration, Purkinje neurons in a mouse model of SCA3 exhibit
      increased intrinsic excitability resulting in depolarization block and the loss
      of the ability to sustain spontaneous repetitive firing. These alterations in
      intrinsic firing are associated with increased inactivation of voltage-activated
      potassium currents. Administration of an activator of calcium-activated potassium
      channels, SKA-31, partially corrects abnormal Purkinje cell firing and improves
      motor function in SCA3 mice. Finally, expression of the disease protein, ataxin
      3, in transfected cells increases the inactivation of Kv3.1 channels and shifts
      the activation of Kv1.2 channels to more depolarized potentials. Our results
      suggest that in SCA3, early Purkinje neuron dysfunction is associated with
      altered physiology of voltage-activated potassium channels. We further suggest
      that the observed changes in Purkinje neuron physiology contribute to disease
      pathogenesis, underlie at least some motor symptoms, and represent a promising
      therapeutic target in SCA3.

PMID- 21900581
TI  - Erythropoietin as a cardioprotective agent: down but not out.

PMID- 21900582
TI  - Polymorphisms of matrix metalloproteinases in myocardial infarction: a meta
      analysis.
AB  - CONTEXT: The literature provides no clear answer as to whether matrix
      metalloproteinases (MMPs) polymorphisms increases risk of myocardial infarction
      (MI). OBJECTIVE: Our purpose was to help clarify the inconsistent findings of
      MMPs polymorphisms and MI susceptibility and identify which MMP polymorphism
      might play an active role in the occurrence of MI. DATA SOURCES: Articles were
      identified by a Medline search and citation tracking. STUDY SELECTION: Eligible
      articles were case-control studies of MMPs polymorphisms and MI which met our
      prespecified criteria. DATA EXTRACTION: Data were independently extracted by two
      authors according to a predefined protocol. Incongruities were settled by
      consensus decision. RESULTS AND CONCLUSIONS: 18 potentially eligible articles
      were identified. In a combined analysis, the 5A allele of the MMP-3 5A/6A
      polymorphism was associated with MI (OR 1.21, 95% CI 1.01 to 1.46, p=0.04),
      suggesting its role in plaque rupture. In the subgroup analysis by ethnicity,
      significantly increased risk was found among East Asians (OR 1.39, 95% CI 1.01 to
      1.91, p=0.04), whereas no significant association was detected in Caucasian
      populations. In addition, there were significant associations of the MMP-9 -1562C
      >T polymorphism with MI (OR 1.14, 95% CI 1.02 to 1.27, p=0.02), whereas the
      heterogeneity of the studies showed no significance (I(2)=13.7%, p=0.32). This
      meta-analysis demonstrated that the MMP-3 5A/6A and MMP-9 -1562 C->T
      polymorphisms are risk factors associated with increased MI susceptibility, but
      these associations vary in different ethnic populations.

PMID- 21900583
TI  - The choice of diuretic in hypertension: saving the baby from the bathwater.

PMID- 21900584
TI  - Almanac 2011: stable coronary artery disease. An editorial overview of selected
      research that has driven recent advances in clinical cardiology.

PMID- 21900586
TI  - Clinical assessment of acute heart failure syndromes: emergency department
      through the early post-discharge period.

PMID- 21900587
TI  - Sudden death: managing the patient who survives.

PMID- 21900585
TI  - Effect of erythropoietin as an adjunct to primary percutaneous coronary
      intervention: a randomised controlled clinical trial.
AB  - OBJECTIVE: The acute administration of high-dose erythropoietin (EPO) on
      reperfusing ischaemic myocardium has been reported to halve myocardial infarct
      (MI) size in preclinical studies, but its effect in ST elevation myocardial
      infarction patients undergoing primary percutaneous coronary intervention (PPCI)
      remains unknown. We investigated whether high-dose EPO administered as an adjunct
      to PPCI reduces MI size. DESIGN: Double-blinded, randomised, placebo-controlled.
      SETTING: Single tertiary cardiac centre. PATIENTS: Fifty-one ST elevation
      myocardial infarction patients undergoing PPCI. INTERVENTIONS: Patients were
      randomly assigned to receive either a single intravenous bolus of EPO (50,000 IU)
      prior to PPCI with a further bolus given 24 h later (n=26) or placebo (n=25).
      MAIN OUTCOME MEASURES: MI size measured by 24 h area under the curve troponin T
      and cardiac magnetic resonance imaging performed on day 2 and at 4 months.
      RESULTS: EPO treatment failed to reduce MI size (troponin T area under the curve:
      114.6+/-78 MUg/ml EPO vs 100.8+/-68 MUg/ml placebo; infarct mass by cardiac
      magnetic resonance: 33+/-16 g EPO vs 25+/-16 g placebo; both p>0.05).
      Unexpectedly, EPO treatment doubled the incidence of microvascular obstruction
      (82% EPO vs 47% placebo; p=0.02) and significantly increased indexed left
      ventricular (LV) end-diastolic volumes (84+/-10 ml/m(2) EPO vs 73+/-13 ml/m(2)
      placebo; p=0.003), indexed LV end-systolic volumes (41+/-9 ml/m(2) EPO vs 35+/-11
      ml/m(2) placebo; p=0.035) and indexed myocardial mass (89+/-16 g/m(2) EPO vs 79+/
      11 g/m(2) placebo; p=0.03). At 4 months, there were no significant differences
      between groups. CONCLUSIONS: High-dose EPO administered as an adjunct to PPCI
      failed to reduce MI size. In fact, EPO treatment was associated with an increased
      incidence of microvascular obstruction, LV dilatation and increased LV mass.
      Clinical Trial Registration Information
      http://public.ukcrn.org.uk/search/StudyDetail.aspx?StudyID=4058 Unique
      Identifier=Study ID 4058.

PMID- 21900589
TI  - Imaging the infected heart.
AB  - This Focus discusses the merits of modern imaging techniques for the management
      of patients with suspected or proven infection and also addresses the challenges
      of detecting infective endocarditis early.

PMID- 21900590
TI  - Getting to the root of hydrocephalus.
AB  - The blood-borne lipid lysophosphatidic acid and its receptor contribute to fetal
      onset hydrocephalus, a severe neurological disorder of newborns.

PMID- 21900591
TI  - Hidden immunotherapy targets challenge dogma.
AB  - In this issue of Science Translational Medicine, Guo et al. discuss the
      intriguing possibility that intracellular tumor antigen-specific monoclonal
      antibodies (mAbs) inhibit tumor growth and metastasis and prolong survival of
      tumor-bearing mice. Here, I discuss the implications of using intracellular
      targets in mAb-based immunotherapy as well as the possible underlying mechanisms
      of action.

PMID- 21900592
TI  - Targeting intracellular oncoproteins with antibody therapy or vaccination.
AB  - Antibody-based therapies have better specificity and thus improved efficacy over
      standard chemotherapy regimens, which result in extended survival and improved
      quality of life for cancer patients. Because antibodies are viewed as too large
      to access intracellular locations, antibody therapy has traditionally targeted
      extracellular or secreted proteins expressed by cancer cells. However, many
      oncogenic proteins are found within the cell (such as intracellular
      phosphatases/kinases and transcription factors) and have therefore not been
      pursued for antibody therapies. Here, we explored the possibility of antibody
      therapy or vaccination against intracellular proteins. As proofs of concept, we
      selected three representative intracellular proteins as immunogens for tumor
      vaccine studies: PRL-3 (phosphatase of regenerating liver 3), a cancer-associated
      phosphatase; EGFP (enhanced green fluorescent protein), a general reporter; and
      mT (polyomavirus middle T), the polyomavirus middle T oncoprotein. A variety of
      tumors that expressed these intracellular proteins were clearly inhibited by
      their respective exogenous antibodies or by antigen-induced host antibodies
      (vaccination). These anticancer activities were reproducibly observed in hundreds
      of C57BL/6 tumor-bearing mice and MMTV-PymT transgenic breast tumor mice. Our in
      vivo data suggest that immunotherapies can target not only extracellular but also
      intracellular oncoproteins.

PMID- 21900593
TI  - Activation of ERBB2 signaling causes resistance to the EGFR-directed therapeutic
      antibody cetuximab.
AB  - Cetuximab, an antibody directed against the epidermal growth factor receptor, is
      an effective clinical therapy for patients with colorectal, head and neck, and
      non-small cell lung cancer, particularly for those with KRAS and BRAF wild-type
      cancers. Treatment in all patients is limited eventually by the development of
      acquired resistance, but little is known about the underlying mechanism. Here, we
      show that activation of ERBB2 signaling in cell lines, either through ERBB2
      amplification or through heregulin up-regulation, leads to persistent
      extracellular signal-regulated kinase 1/2 signaling and consequently to cetuximab
      resistance. Inhibition of ERBB2 or disruption of ERBB2/ERBB3 heterodimerization
      restores cetuximab sensitivity in vitro and in vivo. A subset of colorectal
      cancer patients who exhibit either de novo or acquired resistance to cetuximab
      based therapy has ERBB2 amplification or high levels of circulating heregulin.
      Collectively, these findings identify two distinct resistance mechanisms, both of
      which promote aberrant ERBB2 signaling, that mediate cetuximab resistance.
      Moreover, these results suggest that ERBB2 inhibitors, in combination with
      cetuximab, represent a rational therapeutic strategy that should be assessed in
      patients with cetuximab-resistant cancers.

PMID- 21900594
TI  - Lysophosphatidic acid signaling may initiate fetal hydrocephalus.
AB  - Fetal hydrocephalus (FH), characterized by the accumulation of cerebrospinal
      fluid, an enlarged head, and neurological dysfunction, is one of the most common
      neurological disorders of newborns. Although the etiology of FH remains unclear,
      it is associated with intracranial hemorrhage. Here, we report that
      lysophosphatidic acid (LPA), a blood-borne lipid that activates signaling through
      heterotrimeric guanosine 5'-triphosphate-binding protein (G protein)-coupled
      receptors, provides a molecular explanation for FH associated with hemorrhage. A
      mouse model of intracranial hemorrhage in which the brains of mouse embryos were
      exposed to blood or LPA resulted in development of FH. FH development was
      dependent on the expression of the LPA(1) receptor by neural progenitor cells.
      Administration of an LPA(1) receptor antagonist blocked development of FH. These
      findings implicate the LPA signaling pathway in the etiology of FH and suggest
      new potential targets for developing new treatments for FH.

PMID- 21900595
TI  - Alcohol intake and colorectal cancer risk by molecularly defined subtypes in a
      prospective study of older women.
AB  - Increased alcohol consumption is a putative colorectal cancer (CRC) risk factor.
      However, existing data are less conclusive for women than men. Also, to date,
      relatively few studies have reported alcohol-related CRC risks based on
      molecularly defined tumor subtypes. We evaluated associations between alcohol
      intake and incident CRC, overall and by microsatellite instability [MSI high (MSI
      H) or MSI low/microsatellite stable (MSI-L/MSS)], CpG island methylator phenotype
      (CIMP positive or CIMP negative), and BRAF mutation (mutated or wild-type) status
      in the prospective, population-based Iowa Women's Health Study (IWHS; n =
      41,836). Subjects were 55 to 69 years at baseline (1986), and exposure data were
      obtained by self-report. Incident CRCs were prospectively identified and
      archived, paraffin-embedded tissue specimens were collected from 732
      representative cases, diagnosed through December 31, 2002. Multivariate Cox
      regression models were fit to estimate relative risks (RR) and 95% confidence
      intervals (CI). Among alcohol consumers, the median intake (range) was 3.4 (0.9
      292.8) g/d. Compared with nonconsumers, alcohol intake levels of 3.4 g/d or less
      (RR = 1.00; 95% CI, 0.86-1.15) and more than 3.4 g/d (RR = 1.06; 95% CI, 0.91
      1.24) were not significantly associated with overall CRC risk. Analyses based on
      alcohol intake levels of 30 g/d or less and more than 30 g/d or quartile
      distributions yielded similar risk estimates. Null associations were also
      observed between each alcohol intake level and the MSI-, CIMP- or, BRAF-defined
      CRC subtypes (P > 0.05 for each comparison). These data do not support an adverse
      effect from alcohol intake on CRC risk, overall or by specific molecularly
      defined subtypes, among older women.

PMID- 21900596
TI  - Fluorinated COX-2 inhibitors as agents in PET imaging of inflammation and cancer.
AB  - COX-2 is a major contributor to the inflammatory response and cancer progression
      so it is an important target for prevention and therapy. COX-2 is absent or
      expressed at low levels in most epithelial cells but is found at high levels in
      inflammatory lesions, and many premalignant and malignant tumors. Thus, it is an
      attractive target for molecular imaging. We report a series of novel fluorinated
      imaging agents, derived from indomethacin or celecoxib that selectively inhibit
      COX-2. The most promising lead, compound 7, was a fluorinated derivative of
      celecoxib. Kinetic analysis revealed that this fluorinated compound is a slow,
      tight-binding inhibitor of COX-2 and exhibits minimal inhibitory activity against
      COX-1. Efficient incorporation of (18)F into compound 7 by radiochemical
      synthesis and intravenous injection provided sufficient signal for in vivo
      positron emission tomography (PET) imaging. Selective uptake of (18)F-7 was
      observed in inflamed rat paws compared with the noninflamed contralateral paws
      and uptake was blocked by pretreatment with the COX-2 inhibitor, celecoxib.
      Uptake of (18)F-7 was not observed when inflammation was induced in COX-2-null
      mice. In nude mice bearing both a COX-2-expressing human tumor xenograft (1483)
      and a COX-2-negative xenograft (HCT116), (18)F-7 selectively accumulated in the
      COX-2-expressing tumor. Accumulation was blocked by pretreatment of the animals
      with celecoxib. The in vitro and in vivo properties of compound 7 suggest it will
      be a useful probe for early detection of cancer and for evaluation of the COX-2
      status of premalignant and malignant tumors.

PMID- 21900598
TI  - Independent genome reduction and phylogenetic reclassification of the oceanic
      SAR11 clade.
AB  - The SAR11 clade, here represented by Candidatus Pelagibacter ubique, is the most
      successful group of bacteria in the upper surface waters of the oceans. In
      contrast to previous studies that have associated the 1.3 Mb genome of Ca.
      Pelagibacter ubique with the less than 1.5 Mb genomes of the Rickettsiales, our
      phylogenetic analysis suggests that Ca. Pelagibacter ubique is most closely
      related to soil and aquatic Alphaproteobacteria with large genomes. This implies
      that the SAR11 clade and the Rickettsiales have undergone genome reduction
      independently. A gene flux analysis of 46 representative alphaproteobacterial
      genomes indicates the loss of more than 800 genes in each of Ca. Pelagibacter
      ubique and the Rickettsiales. Consistent with their different phylogenetic
      affiliations, the pattern of gene loss differs with a higher loss of genes for
      repair and recombination processes in Ca. Pelagibacter ubique as compared with a
      more extensive loss of genes for biosynthetic functions in the Rickettsiales.
      Some of the lost genes in Ca. Pelagibacter ubique, such as mutLS, recFN, and
      ruvABC, are conserved in all other alphaproteobacterial genomes including the
      small genomes of the Rickettsiales. The mismatch repair genes mutLS are absent
      from all currently sequenced SAR11 genomes and also underrepresented in the
      global ocean metagenome data set. We hypothesize that the unique loss of genes
      involved in repair and recombination processes in Ca. Pelagibacter ubique has
      been driven by selection and that this helps explain many of the characteristics
      of the SAR11 population, such as the streamlined genomes, the long branch
      lengths, the high recombination frequencies, and the extensive sequence
      divergence within the population.

PMID- 21900597
TI  - The impact of common genetic variations in genes of the sex hormone metabolic
      pathways on steroid hormone levels and prostate cancer aggressiveness.
AB  - Our previous work suggested that there was no significant association between
      plasma steroid hormone levels and prostate cancer tumor grade at diagnosis. In
      this study, we systematically tested the hypothesis that inherited variations in
      the androgen and estrogen metabolic pathways may be associated with plasma levels
      of steroid hormones, or prostate cancer aggressiveness at diagnosis. Plasma
      hormone levels including total testosterone, total estradiol, and sex hormone
      binding globulin were measured in a cohort of 508 patients identified with
      localized prostate cancer. D'Amico risk classification at diagnosis was also
      determined. A total of 143 single-nucleotide polymorphisms (SNPs) from 30 genes
      that are involved in androgen and estrogen metabolism were selected for analysis.
      The global association of genotypes with plasma hormone levels and prostate
      cancer aggressiveness (D'Amico risk classification) was statistically analyzed. Q
      values were estimated to account for multiple testing. We observed significant
      associations between plasma testosterone level and SNPs in HSD17B2 (rs1424151),
      HSD17B3 (rs9409407), and HSD17B1 (rs12602084), with P values of 0.002, 0.006, and
      0.006, respectively. We also observed borderline significant associations between
      prostate aggressiveness at diagnosis and SNPs in AKR1C1 (rs11252845; P = 0.005),
      UGT2B15 (rs2045100; P = 0.007), and HSD17B12 (rs7932905; P = 0.008). No
      individual SNP was associated with both clinical variables. Genetic variants of
      genes in hormone metabolic pathways may influence plasma androgen levels or
      prostate cancer aggressiveness. However, it seems that the inherited variations
      affecting plasma hormone levels differ from those affecting disease
      aggressiveness.

PMID- 21900600
TI  - Inappropriate model rejects independent domestications of indica and japonica
      rice.

PMID- 21900599
TI  - Evolution at the subgene level: domain rearrangements in the Drosophila
      phylogeny.
AB  - Although the possibility of gene evolution by domain rearrangements has long been
      appreciated, current methods for reconstructing and systematically analyzing gene
      family evolution are limited to events such as duplication, loss, and sometimes,
      horizontal transfer. However, within the Drosophila clade, we find domain
      rearrangements occur in 35.9% of gene families, and thus, any comprehensive study
      of gene evolution in these species will need to account for such events. Here, we
      present a new computational model and algorithm for reconstructing gene evolution
      at the domain level. We develop a method for detecting homologous domains between
      genes and present a phylogenetic algorithm for reconstructing maximum parsimony
      evolutionary histories that include domain generation, duplication, loss, merge
      (fusion), and split (fission) events. Using this method, we find that genes
      involved in fusion and fission are enriched in signaling and development,
      suggesting that domain rearrangements and reuse may be crucial in these
      processes. We also find that fusion is more abundant than fission, and that
      fusion and fission events occur predominantly alongside duplication, with 92.5%
      and 34.3% of fusion and fission events retaining ancestral architectures in the
      duplicated copies. We provide a catalog of ~9,000 genes that undergo domain
      rearrangement across nine sequenced species, along with possible mechanisms for
      their formation. These results dramatically expand on evolution at the subgene
      level and offer several insights into how new genes and functions arise between
      species.

PMID- 21900601
TI  - Extensive changes to alternative splicing patterns following allopolyploidy in
      natural and resynthesized polyploids.
AB  - Polyploidy has been a common process during the evolution of eukaryotes,
      especially plants, leading to speciation and the evolution of new gene functions.
      Gene expression levels and patterns can change, and gene silencing can occur in
      allopolyploids--phenomena sometimes referred to as "transcriptome shock."
      Alternative splicing (AS) creates multiple mature mRNAs from a single type of
      precursor mRNA. Here we examined the evolution of AS patterns after polyploidy,
      with natural and two resynthesized allotetraploid Brassica napus lines, using RT
      PCR and sequencing assays of 82 AS events in duplicated gene pairs (homeologs).
      Comparing the AS patterns between the two homeologs in natural B. napus revealed
      that many of the gene pairs show different AS patterns, with a few showing
      variation that was organ specific or induced by abiotic stress treatments. In the
      resynthesized allotetraploids, 26-30% of the duplicated genes showed changes in
      AS compared with the parents, including many cases of AS event loss after
      polyploidy. Parallel losses of many AS events after allopolyploidy were detected
      in the two independently resynthesized lines. More changes occurred in parallel
      between the two lines than changes specific to each line. The PASTICCINO gene
      showed partitioning of two AS events between the two homeologs in the
      resynthesized allopolyploids. AS changes after allopolyploidy were much more
      common than homeolog silencing. Our findings indicate that AS patterns can change
      rapidly after polyploidy, that many genes are affected, and that AS changes are
      an important component of the transcriptome shock experienced by new
      allopolyploids.

PMID- 21900602
TI  - Natural killer cells direct hemochorial placentation by regulating hypoxia
      inducible factor dependent trophoblast lineage decisions.
AB  - Natural killer (NK) cells are recruited into the uterine stroma during
      establishment of the hemochorial placenta and are proposed regulators of uterine
      spiral artery remodeling. Failures in uterine spiral artery remodeling are linked
      to diseases of pregnancy. This prompted an investigation of the involvement of NK
      cells in placentation. NK cell depletion decreased the delivery of proangiogenic
      factors and delayed uterine spiral artery development, leading to decreased
      oxygen tension at the placentation site, stabilized hypoxia-inducible factor 1A
      protein, and redirected trophoblast differentiation to an invasive phenotype.
      Trophoblast cells replaced the endothelium of uterine spiral arteries extending
      the depth of the placental vascular bed and accelerating vessel remodeling.
      Hypoxia-regulated trophoblast lineage decisions, including expansion of invasive
      trophoblast, could be reproduced in vitro by using rat trophoblast stem cells and
      were dependent on hypoxia-inducible factor signaling. We conclude that NK cells
      guide hemochorial placentation through controlling a hypoxia-sensitive adaptive
      reflex regulating trophoblast lineage decisions.

PMID- 21900603
TI  - Myeloid-specific estrogen receptor alpha deficiency impairs metabolic homeostasis
      and accelerates atherosclerotic lesion development.
AB  - ERalpha is expressed in macrophages and other immune cells known to exert
      dramatic effects on glucose homeostasis. We investigated the impact of ERalpha
      expression on macrophage function to determine whether hematopoietic or myeloid
      specific ERalpha deletion manifests obesity-induced insulin resistance in mice.
      Indeed, altered plasma adipokine and cytokine levels, glucose intolerance,
      insulin resistance, and increased adipose tissue mass were observed in animals
      harboring a hematopoietic or myeloid-specific deletion of ERalpha. A similar
      obese phenotype and increased atherosclerotic lesion area was displayed in LDL
      receptor-KO mice transplanted with ERalpha(-/-) bone marrow. In isolated
      macrophages, ERalpha was necessary for repression of inflammation, maintenance of
      oxidative metabolism, IL-4-mediated induction of alternative activation, full
      phagocytic capacity in response to LPS, and oxidized LDL-induced expression of
      ApoE and Abca1. Furthermore, we identified ERalpha as a direct regulator of
      macrophage transglutaminase 2 expression, a multifunctional atheroprotective
      enzyme. Our findings suggest that diminished ERalpha expression in
      hematopoietic/myeloid cells promotes aspects of the metabolic syndrome and
      accelerates atherosclerosis in female mice.

PMID- 21900604
TI  - Affinity maturation of human CD4 by yeast surface display and crystal structure
      of a CD4-HLA-DR1 complex.
AB  - Helper T-cell activation generally requires the coreceptor CD4, which binds MHC
      class II molecules. A remarkable feature of the CD4-MHC class II interaction is
      its exceptionally low affinity, which ranges from K(D) = ~200 MUM to >2 mM.
      Investigating the biological role of the much lower affinity of this interaction
      than those of other cell-cell recognition molecules will require CD4 mutants with
      enhanced binding to MHC class II for testing in models of T-cell development. To
      this end, we used in vitro-directed evolution to increase the affinity of human
      CD4 for HLA-DR1. A mutant CD4 library was displayed on the surface of yeast and
      selected using HLA-DR1 tetramers or monomers, resulting in isolation of a CD4
      clone containing 11 mutations. Reversion mutagenesis showed that most of the
      affinity increase derived from just two substitutions, Gln40Tyr and Thr45Trp. A
      CD4 variant bearing these mutations bound HLA-DR1 with K(D) = 8.8 MUM, compared
      with >400 MUM for wild-type CD4. To understand the basis for improved affinity,
      we determined the structure of this CD4 variant in complex with HLA-DR1 to 2.4 A
      resolution. The structure provides an atomic-level description of the CD4-binding
      site on MHC class II and reveals how CD4 recognizes highly polymorphic HLA-DR, 
      DP, and -DQ molecules by targeting invariant residues in their alpha2 and beta2
      domains. In addition, the CD4 mutants reported here constitute unique tools for
      probing the influence of CD4 affinity on T-cell activation and development.

PMID- 21900605
TI  - Metabolic state of glioma stem cells and nontumorigenic cells.
AB  - Gliomas contain a small number of treatment-resistant glioma stem cells (GSCs),
      and it is thought that tumor regrowth originates from GSCs, thus rendering GSCs
      an attractive target for novel treatment approaches. Cancer cells rely more on
      glycolysis than on oxidative phosphorylation for glucose metabolism, a phenomenon
      used in 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography imaging of
      solid cancers, and targeting metabolic pathways in cancer cells has become a
      topic of considerable interest. However, if GSCs are indeed important for tumor
      control, knowledge of the metabolic state of GSCs is needed. We hypothesized that
      the metabolism of GSCs differs from that of their progeny. Using a unique imaging
      system for GSCs, we assessed the oxygen consumption rate, extracellular
      acidification rate, intracellular ATP levels, glucose uptake, lactate production,
      PKM1 and PKM2 expression, radiation sensitivity, and cell cycle duration of GSCs
      and their progeny in a panel of glioma cell lines. We found GSCs and progenitor
      cells to be less glycolytic than differentiated glioma cells. GSCs consumed less
      glucose and produced less lactate while maintaining higher ATP levels than their
      differentiated progeny. Compared with differentiated cells, GSCs were
      radioresistant, and this correlated with a higher mitochondrial reserve capacity.
      Glioma cells expressed both isoforms of pyruvate kinase, and inhibition of either
      glycolysis or oxidative phosphorylation had minimal effect on energy production
      in GSCs and progenitor cells. We conclude that GSCs rely mainly on oxidative
      phosphorylation. However, if challenged, they can use additional metabolic
      pathways. Therefore, targeting glycolysis in glioma may spare GSCs.

PMID- 21900606
TI  - Hybrid four-headed myosin motor engineered with antagonistic motor domains.

PMID- 21900608
TI  - Pulsed quantum optomechanics.
AB  - Studying mechanical resonators via radiation pressure offers a rich avenue for
      the exploration of quantum mechanical behavior in a macroscopic regime. However,
      quantum state preparation and especially quantum state reconstruction of
      mechanical oscillators remains a significant challenge. Here we propose a scheme
      to realize quantum state tomography, squeezing, and state purification of a
      mechanical resonator using short optical pulses. The scheme presented allows
      observation of mechanical quantum features despite preparation from a thermal
      state and is shown to be experimentally feasible using optical microcavities. Our
      framework thus provides a promising means to explore the quantum nature of
      massive mechanical oscillators and can be applied to other systems such as
      trapped ions.

PMID- 21900610
TI  - Development and characterization of 10 microsatellite loci in Paeonia lactiflora
      (Paeoniaceae).
AB  - PREMISE OF THE STUDY: Microsatellite primers were developed in Paeonia
      lactiflora for further population genetic studies. * METHODS AND RESULTS: Ten
      dinucleotide microsatellite markers were developed using an enriched genomic
      library. They were identified in 58 individuals, and nine markers were also
      amplified in its cultivars. The number of alleles per locus ranged from three to
      11, with a mean of six. The observed and expected heterozygosities ranged from
      0.1662 to 0.9140 and from 0.0841 to 0.8157, respectively. * CONCLUSIONS: These
      microsatellite markers will facilitate further studies on population genetics
      variation and genetic structure of P. lactiflora.

PMID- 21900609
TI  - Carbon monoxide poisoning is prevented by the energy costs of conformational
      changes in gas-binding haemproteins.
AB  - Carbon monoxide (CO) is a product of haem metabolism and organisms must evolve
      strategies to prevent endogenous CO poisoning of haemoproteins. We show that
      energy costs associated with conformational changes play a key role in preventing
      irreversible CO binding. AxCYTcp is a member of a family of haem proteins that
      form stable 5c-NO and 6c-CO complexes but do not form O(2) complexes. Structure
      of the AxCYTcp-CO complex at 1.25 A resolution shows that CO binds in two
      conformations moderated by the extent of displacement of the distal residue Leu16
      toward the haem 7-propionate. The presence of two CO conformations is confirmed
      by cryogenic resonance Raman data. The preferred linear Fe-C-O arrangement (170
      +/- 8 degrees ) is accompanied by a flip of the propionate from the distal to
      proximal face of the haem. In the second conformation, the Fe-C-O unit is bent
      (158 +/- 8 degrees ) with no flip of propionate. The energetic cost of the CO
      induced Leu-propionate movements is reflected in a 600 mV (57.9 kJ mol(-1))
      decrease in haem potential, a value in good agreement with density functional
      theory calculations. Substitution of Leu by Ala or Gly (structures determined at
      1.03 and 1.04 A resolutions) resulted in a haem site that binds CO in the linear
      mode only and where no significant change in redox potential is observed.
      Remarkably, these variants were isolated as ferrous 6c-CO complexes, attributable
      to the observed eight orders of magnitude increase in affinity for CO, including
      an approximately 10,000-fold decrease in the rate of dissociation. These new
      findings have wide implications for preventing CO poisoning of gas-binding haem
      proteins.

PMID- 21900611
TI  - Consequences of plant-pollinator and floral-herbivore interactions on the
      reproductive success of the Canary Islands endemic Canarina canariensis
      (Campanulaceae).
AB  - PREMISE OF THE STUDY: Pollination is a critical phase for plant reproduction,
      but ecological and evolutionary outcomes by pollinators may be counteracted by
      floral herbivores. These interacting assemblages may also be altered (directly or
      indirectly) by introduced species, especially on oceanic islands. In this study,
      we analyzed the effects of opportunistic nectar-feeding passerine birds and
      native (semi-slugs) and introduced (rats) floral herbivores on the reproductive
      success of Canarina canariensis. * METHODS: Manual pollination experiments were
      conducted to determine plant breeding system and pollen limitation. We also
      identified floral visitors and their visitation frequencies by censuses. Bird
      pollination effectiveness was evaluated by selective exclosures. The intensity of
      floral herbivory by native vs. introduced herbivores and its effect on plant
      fitness was estimated in different areas within the Canary island of Tenerife. *
      KEY RESULTS: Canarina canariensis had a very low spontaneous selfing ability and
      high pollen limitation, despite being self-compatible. Birds increased fruit set
      and the percentage of viable seeds per fruit, while florivores, the principal
      floral visitors, reduced them. Semi-slugs mainly consumed male reproductive
      organs, while rats preferred female. There was a strong within-island spatial
      variation in the herbivory intensity. * CONCLUSIONS: Opportunistic nectar-feeding
      birds increase the production of viable seeds in C. canariensis, but their
      beneficial effects are counteracted by the high incidence of floral herbivory.
      Because native semi-slugs damaged anthers more frequently than did introduced
      rats, these florivores may differ in their effects on male and female plant
      reproductive success.

PMID- 21900612
TI  - What does it take to resolve relationships and to identify species with molecular
      markers? An example from the epiphytic Rhipsalideae (Cactaceae).
AB  - PREMISE OF THE STUDY: The Cactaceae are a major New World plant family and
      popular in horticulture. Still, taxonomic units and species limits have been
      difficult to define, and molecular phylogenetic studies so far have yielded
      largely unresolved trees, so relationships within Cactaceae remain insufficiently
      understood. This study focuses on the predominantly epiphytic tribe Rhipsalideae
      and evaluates the utility of a spectrum of plastid genomic regions. * METHODS: We
      present a phylogenetic study including 52 of the 53 Rhipsalideae species and all
      the infraspecific taxa. Seven regions (trnK intron, matK, rbcL, rps3-rpl16, rpl16
      intron, psbA-trnH, trnQ-rps16), ca. 5600 nucleotides (nt) were sequenced per
      sample. The regions used were evaluated for their phylogenetic performance and
      performance in DNA-based species recognition based on operational taxonomic units
      (OTUs) defined beforehand. * KEY RESULTS: The Rhipsalideae are monophyletic and
      contain five clades that correspond to the genera Rhipsalis, Lepismium,
      Schlumbergera, Hatiora, and Rhipsalidopsis. The species-level tree was well
      resolved and supported; the rpl16 and trnK introns yielded the best phylogenetic
      signal. Although the psbA-trnH and trnQ-rps16 spacers were the most successful
      individual regions for OTU identification, their success rate did not
      significantly exceed 70%. The highest OTU identification rate of 97% was found
      using the combination of psbA-trnH, rps3-rpl16, trnK intron, and trnQ-rps16 as a
      minimum possible marker length (ca. 1660 nt). * CONCLUSIONS: The phylogenetic
      performance of a marker is not determined by the level of sequence variability,
      and species discrimination power does not necessarily correlate with phylogenetic
      utility.

PMID- 21900613
TI  - Reduction in radiation dose in mercaptoacetyltriglycerine renography with
      enhanced planar processing.
AB  - PURPOSE: To determine the minimum dose of technetium 99m ((99m)Tc)
      mercaptoacetyltriglycerine (MAG3) needed to perform dynamic renal scintigraphy in
      the pediatric population without loss of diagnostic quality or accurate
      quantification of renal function and to investigate whether adaptive noise
      reduction could help further reduce the minimum dose required. MATERIALS AND
      METHODS: Approval for this retrospective study was obtained from the
      institutional review board, with waiver of informed consent. A retrospective
      review was conducted in 33 pediatric patients consecutively referred for a
      (99m)Tc-MAG3 study. In each patient, a 20-minute dynamic study was performed
      after administration of 7.4 MBq/kg. Binomial subsampling was used to simulate
      studies performed with 50%, 30%, 20%, and 10% of the administered dose. Four
      nuclear medicine physicians independently reviewed the original and subsampled
      images, with and without noise reduction, for image quality. Two observers
      independently performed a quantitative analysis of renal function. Subjective
      rater confidence was analyzed by using a logistic regression model, and the
      quantitative analysis was performed by using the paired Student t test. RESULTS:
      Reducing the administered dose to 30% did not substantially affect image quality,
      with or without noise reduction. When the dose was reduced to 20%, there was a
      slight but significant decrease (P = .0074) in image quality, which resolved with
      noise reduction. Reducing the dose to 10% caused a decrease in image quality (P =
      .0003) that was not corrected with noise reduction. However, the dose could be
      reduced to 10% without a substantial change in the quantitative evaluation of
      renal function independent of the application of noise reduction. CONCLUSION:
      Decreasing the dose of (99m)Tc-MAG3 from 7.4 to 2.2 MBq/kg did not compromise
      image quality. With noise reduction, the dose can be reduced to 1.5 MBq/kg
      without subjective loss in image quality. The quantitative evaluation of renal
      function was not substantially altered, even with a theoretical dose as low as
      0.74 MBq/kg.

PMID- 21900614
TI  - Knee cartilage T2 characteristics and evolution in relation to morphologic
      abnormalities detected at 3-T MR imaging: a longitudinal study of the normal
      control cohort from the Osteoarthritis Initiative.
AB  - PURPOSE: To determine the frequency of degenerative knee morphologic
      abnormalities in asymptomatic individuals by using 3-T magnetic resonance (MR)
      imaging and to investigate the characteristics and evolution of cartilage T2
      values in relation to morphologic abnormalities with a longitudinal study.
      MATERIALS AND METHODS: The study was approved by the institutional review board
      and was compliant with HIPAA. Ninety-five asymptomatic subjects aged 45-78 years
      who were free of risk factors for osteoarthritis (OA) were selected from the
      Osteoarthritis Initiative normal control cohort and examined with radiography and
      3-T MR imaging. Data obtained at both baseline and 2-year follow-up were
      analyzed. OA-related knee abnormalities were analyzed by using the whole-organ MR
      imaging score (WORMS). Cartilage T2 maps were generated by using sagittal two
      dimensional multiecho spin-echo images of the right knee. Statistical
      significance was determined with the Student t test, the paired t test, a mixed
      random effects model, one-way analysis of variance, and a multiple linear
      regression model. RESULTS: Knee abnormalities were identified with a high
      frequency (90% at baseline and 92% at 2-year follow-up). The prevalence of
      hyaline cartilage lesions was particularly high (86% at baseline and 84% at
      follow-up). A significant longitudinal increase in T2 was detected in the
      tibiofemoral cartilage but not the patellofemoral cartilage (P = .0072). The
      longitudinal change in T2 was significantly associated with worsening of the
      cartilage WORMS (P = .038). CONCLUSION: Asymptomatic subjects have a high
      frequency of OA-related morphologic abnormalities. A significant increase in
      tibiofemoral cartilage T2 was detected over the 2-year period. A greater increase
      in T2 was associated with increased progression of cartilage morphologic
      abnormalities.

PMID- 21900615
TI  - Multivoxel proton MR spectroscopy used to distinguish anterior cingulate
      metabolic abnormalities in patients with schizophrenia.
AB  - PURPOSE: To test the hypothesis that anterior cingulate cortex (ACC) subregions
      in patients with schizophrenia are metabolically different from those in healthy
      control subjects. MATERIALS AND METHODS: This institutional review board-approved
      study was HIPAA compliant, and all participants provided written informed
      consent. Twenty-two patients with schizophrenia (13 male, nine female; 39.4 years
      +/- 10.6 [standard deviation]) and 11 age- and sex-matched control subjects
      (seven male, four female; 35.5 years +/- 10.7) underwent magnetic resonance (MR)
      imaging and three-dimensional 3-T voxel proton MR spectroscopy to measure
      absolute rostral and caudal ACC N-acetylaspartate (NAA), creatine (Cr), and
      choline (Cho) concentrations. Exact Mann-Whitney test was used to compare patient
      data with control data, paired-sample Wilcoxon signed rank test was used to
      compare subregions within groups, and receiver operating characteristic curve
      analysis was used to assess sensitivity and specificity in diagnosis of
      schizophrenia. RESULTS: There were no significant metabolic differences between
      patients and control subjects or between ACC subregions in control subjects. In
      patients, rostral ACC NAA and Cr concentrations were significantly lower than
      those in caudal ACC (6.2 mM +/- 1.3 vs 7.1 mM +/- 1.3, P < .01; 5.7 mmol/L +/-
      1.4 vs 6.3 mmol/L +/- 1.6, P < .01; respectively); however, this did not hold
      true for Cho concentrations (1.7 mmol/L +/- 0.5 vs 1.8 mmol/L +/- 0.5). For
      individual differences between caudal and rostral measurements, only NAA in
      patients was different from that in control subjects (0.9 mmol/L +/- 1.3 vs -0.1
      mmol/L +/- 0.5, P < .01), enabling prediction of schizophrenia with 68%
      sensitivity and 91% specificity, for a difference of more than 0.4. CONCLUSION:
      Significant differences between caudal and rostral NAA concentration are found in
      ACC of patients with schizophrenia but not in ACC of healthy control subjects,
      indicating that neuronal density or integrity differences between ACC subregions
      may be characteristic of the disease.

PMID- 21900616
TI  - Contrast-enhanced MR angiography of the abdomen with highly accelerated
      acquisition techniques.
AB  - PURPOSE: To demonstrate that highly accelerated (net acceleration factor [R(net)]
      >= 10) acquisition techniques can be used to generate three-dimensional (3D)
      subsecond timing images, as well as diagnostic-quality high-spatial-resolution
      contrast material-enhanced (CE) renal magnetic resonance (MR) angiograms with a
      single split dose of contrast material. MATERIALS AND METHODS: All studies were
      approved by the institutional review board and were HIPAA compliant; written
      consent was obtained from all participants. Twenty-two studies were performed in
      10 female volunteers (average age, 47 years; range, 27-62 years) and six patients
      with renovascular disease (three women; average age, 48 years; range, 37-68
      years; three men; average age, 60 years; range, 50-67 years; composite average
      age, 54 years; range, 38-68 years). The two-part protocol consisted of a low-dose
      (2 mL contrast material) 3D timing image with approximate 1-second frame time,
      followed by a high-spatial-resolution (1.0-1.6-mm isotropic voxels) breath-hold
      3D renal MR angiogram (18 mL) over the full abdominal field of view. Both
      acquisitions used two-dimensional (2D) sensitivity encoding acceleration factor
      (R) of eight and 2D homodyne (HD) acceleration (R(HD)) of 1.4-1.8 for R(net) = R
      . R(HD) of 10 or higher. Statistical analysis included determination of mean
      values and standard deviations of image quality scores performed by two
      experienced reviewers with use of eight evaluation criteria. RESULTS: The 2-mL 3D
      time-resolved image successfully portrayed progressive arterial filling in all 22
      studies and provided an anatomic overview of the vasculature. Successful timing
      was also demonstrated in that the renal MR angiogram showed adequate or excellent
      portrayal of the main renal arteries in 21 of 22 studies. CONCLUSION: Two
      dimensional acceleration techniques with R(net) of 10 or higher can be used in CE
      MR angiography to acquire (a) a 3D image series with 1-second frame time,
      allowing accurate bolus timing, and (b) a high-spatial-resolution renal
      angiogram. SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110242/-/DC1.

PMID- 21900617
TI  - Screening breast MR imaging in women with a history of lobular carcinoma in situ.
AB  - PURPOSE: To assess the utility of screening magnetic resonance (MR) imaging in
      the detection of otherwise occult breast cancers in women with a history of
      lobular carcinoma in situ (LCIS). MATERIALS AND METHODS: This HIPAA-compliant
      study received institutional review board approval. The need for informed consent
      was waived. Retrospective review of the database yielded 670 screening breast MR
      studies obtained between January 2003 and September 2008 in 220 women with a
      history of LCIS. MR and mammographic findings were reviewed. Number of cancers
      diagnosed, method of detection, and tumor characteristics were examined. The
      cumulative incidence of developing breast cancer as detected with MR imaging and
      mammography was calculated. Breast density was examined as a prognostic factor in
      the cumulative incidence analysis. RESULTS: Biopsy was recommended in 63 lesions
      seen in 58 (9%) of 670 screening MR studies. Eight additional lesions were
      identified at short-term follow-up MR imaging for a total of 71 lesions in 59
      patients. Twelve cancers (20%) were identified in 60 lesions sampled. Biopsy was
      recommended in 26 additional lesions identified at mammography; biopsy was
      performed in 25 of these lesions and revealed malignancy in five (20%). Overall,
      17 cancers were detected in 14 patients during the study period. Of these, 12
      were detected with MR imaging alone, and five were detected with mammography
      alone. Of the 12 cancers detected at MR imaging, there were nine invasive cancers
      and three cases of ductal carcinoma in situ (DCIS). Of the five cancers detected
      at mammography, two were invasive and three were DCIS. CONCLUSION: MR imaging is
      a useful adjunct modality with which to screen women with a history of LCIS at
      high-risk of developing breast cancer, resulting in a 4.5% incremental cancer
      detection rate. Sensitivity in the detection of breast cancers with a combination
      of MR imaging and mammography was higher than sensitivity of either modality
      alone.

PMID- 21900618
TI  - Results of MR imaging screening for breast cancer in high-risk patients with
      lobular carcinoma in situ.
AB  - PURPOSE: To determine the outcome of screening breast magnetic resonance (MR)
      imaging examinations performed in patients with lobular carcinoma in situ (LCIS)
      at the authors' institution. MATERIALS AND METHODS: This study was approved by
      the institutional review board and was compliant with HIPAA. Retrospective review
      of screening breast MR imaging examinations at the institution from 1996 through
      September 2009 was performed in patients with prior biopsies demonstrating LCIS.
      Patients with prior breast cancer diagnosis were excluded. American College of
      Radiology Breast Imaging Reporting and Data System (BI-RADS) recommendations were
      recorded. Pathologic results of all consequent biopsies were obtained from the
      electronic medical records. RESULTS: A total of 445 breast MR examinations in 198
      patients with LCIS were identified. Of these, 308 were screening examinations in
      134 patients. One patient was a BRCA mutation carrier and was excluded. Of the
      remaining 307 screening examinations, 254 (82.7%) had BI-RADS category 1 or 2
      findings; 27 (8.8%) had BI-RADS category 3 findings; and 27 (8.8%) had B-IRADS
      category 4 or 5 findings. Of the 27 studies that led to a biopsy recommendation,
      10 (37%) yielded benign pathologic findings, five (18.5%) yielded malignant
      pathologic findings, and seven (25.9%) yielded high-risk lesions. Of the 27
      studies with BI-RADS 3 findings, two (7.4%) resulted in biopsy, findings of both
      were benign. Overall, malignancy was detected in five of 307 screening studies
      (1.6%) and in five of 133 screened patients (3.8%). The positive predictive value
      (PPV) of these screening studies for which biopsy was recommended was 18.5%. The
      PPV 3 (studies for which biopsy was recommended and actually performed, as
      described in the BI-RADS guidelines) was 23.8%. CONCLUSION: Screening breast MR
      imaging helped identify breast cancer in LCIS patients at a rate similar to that
      shown in high-risk populations for whom screening breast MR imaging is currently
      consistently recommended.

PMID- 21900619
TI  - Color and power Doppler US for diagnosing carpal tunnel syndrome and determining
      its severity: a quantitative image processing method.
AB  - PURPOSE: To determine whether intraneural vascularity seen at color Doppler
      ultrasonography (US) can be used to diagnose carpal tunnel syndrome (CTS) and to
      evaluate an image processing method for quantifying the severity of CTS on the
      basis of this vascularity. MATERIALS AND METHODS: This study was approved by the
      university ethics review committee. One hundred one patients with clinical
      evidence of CTS and 55 healthy control subjects were enrolled. Electrodiagnostic
      testing (EDT) was performed in all participants, and the presence of intraneural
      vascularity was evaluated with color Doppler US. An image processing program was
      designed by using software to determine the sum of pixels in the intraneural
      vascular area on power Doppler US scans of the median nerve. The relationship
      between the number of pixels and the severity of the abnormality at EDT was
      determined. RESULTS: The sensitivity (83%) and specificity (89%) of intraneural
      vascularity in the diagnosis of CTS were similar to those of EDT (81% and 84%,
      respectively). Intraneural vascularity was seen in 91.4% of patients with mild
      CTS and 100% of patients with moderate or severe CTS. In participants with
      positive intraneural vascularity, the sum of pixels in the intraneural vascular
      area was significantly higher in patients than in control subjects and paralleled
      the severity of the abnormality at EDT (P < .01). CONCLUSION: Color Doppler US
      can be used to accurately diagnose CTS. By processing the recorded power Doppler
      images and determining the number of pixels in the intraneural vascular area, the
      severity of CTS can be assessed. 2011 SUPPLEMENTAL MATERIAL:
      http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.11110150/-/DC1.

PMID- 21900621
TI  - MR arthrography of the hip: comparison of IDEAL-SPGR volume sequence to standard
      MR sequences in the detection and grading of cartilage lesions.
AB  - PURPOSE: To compare the diagnostic performance of iterative decomposition of
      water and fat with echo asymmetry and least-squares estimation (IDEAL)-spoiled
      gradient-recalled echo (SPGR) with that of standard magnetic resonance (MR)
      arthrography sequences for detecting and grading cartilage lesions within the hip
      joint during MR arthrography. MATERIALS AND METHODS: Following institutional
      review board approval, 67 consecutive hip MR arthrograms were retrospectively
      reviewed independently by three musculoskeletal radiologists and one
      musculoskeletal fellow. IDEAL-SPGR images and the two-dimensional images, the
      latter from the routine MR arthrography protocol, were evaluated at separate
      sittings to grade each articular surface of the hip joint. By using arthroscopy
      as the reference standard, the sensitivity and specificity of the two techniques
      for detecting and grading cartilage lesions were determined. The McNemar test was
      used to compare diagnostic performance. Interreader agreement was calculated
      using Fleiss kappa values. RESULTS: For all readers and surfaces combined, the
      sensitivity and specificity for detecting cartilage lesions was 74% and 77%,
      respectively, for IDEAL-SPGR and 70% and 84%, respectively, for the routine MR
      arthrography protocol. IDEAL-SPGR had similar sensitivity (P = .12) to and
      significantly lower specificity (P < .001) than the routine MR arthrography
      protocol for depicting cartilage lesions. When analyzing the differences in
      sensitivity and specificity by reader, the two readers who had experience with
      IDEAL-SPGR had no significant difference in sensitivity and specificity for
      detecting cartilage lesions between the two sequences. For all readers and
      surfaces combined, IDEAL-SPGR had a higher accuracy in correctly grading
      cartilage lesion (P = .012-.013). Interobserver agreement for detecting cartilage
      lesions did not differ between the two techniques. CONCLUSION: IDEAL-SPGR had
      similar sensitivity and significantly lower specificity for detecting cartilage
      lesions and higher accuracy for grading cartilage lesions than did a routine MR
      arthrography protocol; the lower specificity of IDEAL-SPGR for detecting
      cartilage lesions was not seen in experienced readers.

PMID- 21900620
TI  - Timeliness of follow-up after abnormal screening mammogram: variability of
      facilities.
AB  - PURPOSE: To describe the timeliness of follow-up care in community-based settings
      among women who receive a recommendation for immediate follow-up during the
      screening mammography process and how follow-up timeliness varies according to
      facility and facility-level characteristics. MATERIALS AND METHODS: This was an
      institutional review board-approved and HIPAA-compliant study. Screening
      mammograms obtained from 1996 to 2007 in women 40-80 years old in the Breast
      Cancer Surveillance Consortium were examined. Inclusion criteria were a
      recommendation for immediate follow-up at screening, or subsequent imaging, and
      observed follow-up within 180 days of the recommendation. Recommendations for
      additional imaging (AI) and biopsy or surgical consultation (BSC) were analyzed
      separately. The distribution of time to follow-up care was estimated by using the
      Kaplan-Meier estimator. RESULTS: Data were available on 214,897 AI
      recommendations from 118 facilities and 35,622 BSC recommendations from 101
      facilities. The median time to subsequent follow-up care after recommendation was
      14 days for AI and 16 days for BSC. Approximately 90% of AI follow-up and 81% of
      BSC follow-up occurred within 30 days. Facilities with higher recall rates tended
      to have longer AI follow-up times (P < .001). Over the study period, BSC follow
      up rates at 15 and 30 days improved (P < .001). Follow-up times varied
      substantially across facilities. Timely follow-up was associated with larger
      volumes of the recommended procedures but not notably associated with facility
      type nor observed facility-level characteristics. CONCLUSION: Most patients with
      follow-up returned within 3 weeks of the recommendation.

PMID- 21900622
TI  - Idiopathic normal-pressure hydrocephalus: temporal changes in ADC during cardiac
      cycle.
AB  - PURPOSE: To determine whether temporal changes in apparent diffusion coefficient
      (ADC) over the cardiac cycle are different in patients with idiopathic normal
      pressure hydrocephalus (INPH) as compared with patients with ex vacuo ventricular
      dilatation and healthy control subjects. MATERIALS AND METHODS: This prospective
      study was approved by the institutional review board and was performed only after
      informed consent was obtained from each patient. At 1.5 T,
      electrocardiographically triggered single-shot diffusion echo-planar magnetic
      resonance imaging (b = 0 and 1000 sec/mm(2)) was performed with sensitivity
      encoding and half-scan techniques to minimize bulk motion. DeltaADC was defined
      as the difference between maximum and minimum ADC on a pixel-by-pixel basis over
      20 phases of the cardiac cycle. Mean ADC during the diastolic phase and DeltaADC
      in the frontal white matter were determined in patients with INPH (n = 13),
      patients with ex vacuo ventricular dilatation (n = 8), and healthy volunteers (n
      = 10). Kruskal-Wallis tests were used to determine significance between groups.
      RESULTS: Mean DeltaADC in the INPH group was significantly higher than that in
      the ex vacuo ventricular dilatation and control groups (P < .01 for both). There
      was no significant difference in DeltaADC between the ex vacuo ventricular
      dilatation and control groups (P = .86). There was no significant difference in
      mean ADC during the diastolic phase among groups (P > .05 for all). There was no
      significant correlation between DeltaADC and mean ADC during the diastolic phase
      in any group. CONCLUSION: Determination of fluctuation of ADC over the cardiac
      cycle may render it possible to noninvasively obtain new and more detailed
      information than that provided by standard ADC measurement in suspected INPH,
      potentially facilitating the diagnosis of this disease.

PMID- 21900623
TI  - Quantitative CT assessment of emphysema and airways in relation to lung cancer
      risk.
AB  - PURPOSE: To determine whether quantitative computed tomographic (CT) measurements
      of emphysema and airway dimensions are associated with lung cancer risk in a
      screening population. MATERIALS AND METHODS: Institutional review board approval
      and informed consent for the use of deidentified images were obtained. In this
      retrospective study, CT scans were analyzed from 279 participants in the CT
      screening arm of the National Lung Screening Trial who were diagnosed with lung
      cancer and 279 participants who were not diagnosed with lung cancer after a
      median follow-up period of 6.6 years. Quantitative CT measurements of emphysema
      and right upper lobe apical segmental and subsegmental airway dimensions, and
      multiple patient history-related variables, were compared between the two groups.
      Significant variables were tested in multivariate models for association with
      lung cancer by using multiple logistic regression. RESULTS: The emphysema index
      of percentage upper lung volume less than -950 HU had the strongest association
      with lung cancer (mean, 10.7% [standard deviation, 13.5] in patients vs 7.2%
      [standard deviation, 10.4] in control subjects; P < .001), but the relationship
      was weak (R(2) = 0.015, P < .001, c = 0.57). No CT measures of emphysema had an
      association with lung cancer independent of the patient medical history
      variables. Airway dimensions were not associated with lung cancer. CONCLUSION:
      Quantitative CT measurements of emphysema but not airway dimensions were only
      weakly associated with lung cancer, demonstrating no potential practical value
      for clinical risk stratification.

PMID- 21900624
TI  - Articular cartilage treatment in high-level male soccer players: a prospective
      comparative study of arthroscopic second-generation autologous chondrocyte
      implantation versus microfracture.
AB  - BACKGROUND: Soccer is a highly demanding sport for the knee joint, and chondral
      injuries can cause disabling symptoms that may jeopardize an athlete's career.
      Articular cartilage lesions are difficult to treat, and the increased mechanical
      stress produced by this sport makes their management even more complex.
      HYPOTHESIS: To evaluate whether the regenerative cell-based approach allows these
      highly demanding athletes a better functional recovery compared with the bone
      marrow stimulation approach. STUDY DESIGN: Cohort study; Level of evidence, 2.
      METHODS: Forty-one professional or semiprofessional male soccer players were
      treated from 2000 to 2006 and evaluated prospectively at 2 years and at a final
      7.5-year mean follow-up (minimum, 4 years). Twenty-one patients were treated with
      arthroscopic second-generation autologous chondrocyte implantation (Hyalograft C)
      and 20 with the microfracture technique. The clinical outcome of all patients was
      analyzed using the cartilage standard International Cartilage Repair Society
      (ICRS) evaluation package. The sport activity level was evaluated with the Tegner
      score, and the recovery time was also recorded. RESULTS: A significant
      improvement in all clinical scores from preoperative to final follow-up was found
      in both groups. The percentage of patients who returned to competition was
      similar: 80% in the microfracture group and 86% in the Hyalograft C group.
      Patients treated with microfracture needed a median of 8 months before playing
      their first official soccer game, whereas the Hyalograft C group required a
      median time of 12.5 months (P = .009). The International Knee Documentation
      Committee (IKDC) subjective score showed similar results at 2 years' follow-up
      but significantly better results in the Hyalograft C group at the final
      evaluation (P = .005). In fact, in the microfracture group, results decreased
      over time (from 86.8 +/- 9.7 to 79.0 +/- 11.6, P < .0005), whereas the Hyalograft
      C group presented a more durable outcome with stable results (90.5 +/- 12.8 at 2
      years and 91.0 +/- 13.9 at the final follow-up). CONCLUSION: Despite similar
      success in returning to competitive sport, microfracture allows a faster recovery
      but present a clinical deterioration over time, whereas arthroscopic second
      generation autologous chondrocyte implantation delays the return of high-level
      male soccer players to competition but can offer more durable clinical results.

PMID- 21900625
TI  - Recurrent patellar dislocation in adolescents: medial retinaculum plication
      versus vastus medialis plasty.
AB  - BACKGROUND: The clinical outcome of arthroscopic medial retinaculum plication
      (MRP) compared with vastus medialis plasty (VMP) for recurrent patellar
      dislocation in adolescents is unknown. HYPOTHESIS: Arthroscopic MRP can yield
      similar results to open VMP for recurrent patellar dislocation in adolescents.
      STUDY DESIGN: Randomized controlled clinical trial; Level of evidence, 2.
      METHODS: Sixty adolescent patients were randomly divided into 2 groups to receive
      arthroscopic MRP and open VMP respectively. The patients were followed up at 3,
      6, 12, and 24 months postoperatively and computed tomography (CT) scans were
      taken immediately after operation and at 12 and 24 months postoperatively to
      evaluate the position of the patella. Knee function was evaluated at 24 months
      postoperatively according to the International Knee Documentation Committee
      (IKDC), Kujala, Lysholm, and Tegner rating scales. For those who underwent
      operation more than 3 years previously, an additional review was taken to
      evaluate the latest patellar stability status. RESULTS: The final follow-up time
      was 56.8 +/- 21.5 months (range, 24-92 months) and 59.1 +/- 24.7 months (range,
      24-88 months), respectively, in the MRP and VMP groups. The CT examination showed
      that the correction of the patellar position deteriorated over time in both
      groups. The final patellar position was significantly better than that before
      surgery in the VMP group, but not in the MRP group. The VMP group had
      significantly better clinical results at each follow-up compared with the MRP
      group. The IKDC, Lysholm, Kujala, and Tegner scores were 62.5 +/- 6.2, 70.7 +/-
      5.1, 76.6 +/- 4.8, and 3.9 +/- 0.7, respectively, in the MRP group, and 71.8 +/-
      7.1 (P < .001), 79.4 +/- 5.5 (P < .001), 82.9 +/- 4.8 (P < .001), and 5.1 +/- 1.4
      (P < .001), respectively, in the VMP group at the 2-year follow-up. Five patients
      (17.9%) in the MRP group and 2 patients (7.7%) in the VMP group (P = .267)
      experienced episodes of redislocation at the final follow-up. CONCLUSION:
      Arthroscopic MRP is less reliable for maintaining the corrected position of the
      patella and for functional recovery compared with VMP for recurrent patellar
      dislocation in adolescents.

PMID- 21900626
TI  - Arthroscopic versus open distal clavicle excision: a comparative assessment at
      intermediate-term follow-up.
AB  - BACKGROUND: While few comparative studies exist, it has been suggested that open
      distal clavicle excisions (DCEs) provide inferior results when compared with the
      all-arthroscopic technique. PURPOSE: The purpose of this study was to compare the
      intermediate-term (5-year follow-up) results of patients undergoing arthroscopic
      versus open DCE for the treatment of recalcitrant acromioclavicular joint pain.
      STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: All patients who
      underwent an arthroscopic or open DCE between January 1999 and September 2006
      were reviewed. Forty-eight patients (49 shoulders; 32 arthroscopic, 17 open)
      following DCE without significant glenohumeral pathologic changes were included.
      The mean follow-up for group I (open) and group II (arthroscopic) was 5.3 years
      and 4.2 years, respectively. The American Shoulder and Elbow Surgeons (ASES)
      score, visual analog scale (VAS) pain score, surgical time, and minimum
      radiographic acromioclavicular joint distance were calculated. Each patient
      completed a questionnaire assessing their scar satisfaction, percentage of normal
      shoulder function, and willingness to have the surgery again. Risk factors for
      poor outcomes were analyzed. RESULTS: Arthroscopic patients had significantly
      less pain (P = .035) by VAS (0.61 +/- 1.02) compared with open (1.59 +/- 2.15) at
      final follow-up. There was no significant difference between group I and group II
      with regard to ASES (87.5 +/- 17.6 vs 94.6 +/- 8.6), percentage of normal
      shoulder function (89.7% +/- 12.5 vs 92.9% +/- 8.6), average operative time (53.1
      minutes vs 48 minutes), or radiographic resection distance (12.8 +/- 2.1 mm vs
      9.5 +/- 2.9 mm). In the open group, patients with 16 of 17 shoulders were
      satisfied with their scar and 100% would do it again. In the arthroscopic group,
      patients with 31 of 32 shoulders (97%) were both satisfied and would have the
      surgery again. CONCLUSION: Open and arthroscopic DCE are both effective surgeries
      to treat recalcitrant acromioclavicular joint pain. At intermediate-term follow
      up, they provide similarly good to excellent results with regard to patient
      satisfaction and shoulder function. Although both are effective treatments, less
      residual pain was found using the arthroscopic technique.

PMID- 21900627
TI  - Abnormal tactile temporal discrimination in psychogenic dystonia.
AB  - OBJECTIVE: Neurophysiologic studies demonstrated that patients with primary
      torsion dystonia (PTD) and with psychogenic dystonia (Psy-D) share similar
      abnormalities in the motor system. In this study, we evaluated somatosensory
      function in Psy-D by testing temporal discrimination threshold (TDT), and
      compared the results with those obtained in patients with PTD. METHODS: TDT of
      tactile stimuli was assessed in 10 patients with Psy-D, 10 patients with PTD, and
      16 control subjects. The 2 groups of patients were matched for age, gender,
      disease duration, and distribution of dystonia. Tactile stimuli consisted of
      pairs of non-noxious electrical shocks delivered to the right or left hand at
      interstimulus interval increasing from 0 to 400 msec, in 10-msec steps. TDT was
      defined as the value at which subjects recognized the 2 stimuli as asynchronous.
      RESULTS: TDT was higher in Psy-D and PTD compared to control subjects, for both
      the right and the left hand. In a subgroup of patients with unilateral dystonia
      (Psy-D = 4, PTD = 5), TDT did not differ between the affected and the unaffected
      side in both groups of patients. Disease duration was not correlated to the
      increased TDT value. CONCLUSIONS: Our study suggests an impaired processing of
      somatosensory inputs in both Psy-D and PTD. These abnormalities might represent a
      neurophysiological trait predisposing to develop a dystonic posture triggered by
      psychiatric and psychological factors.

PMID- 21900628
TI  - Advanced glycation end product level, diabetes, and accelerated cognitive aging.
AB  - OBJECTIVE: Several studies report that diabetes increases risk of cognitive
      impairment; some have hypothesized that advanced glycation end products (AGEs)
      underlie this association. AGEs are cross-linked products that result from
      reactions between glucose and proteins. Little is known about the association
      between peripheral AGE concentration and cognitive aging. METHODS: We
      prospectively studied 920 elders without dementia, 495 with diabetes and 425 with
      normal glucose (mean age 74.0 years). Using mixed models, we examined baseline
      AGE concentration, measured with urine pentosidine and analyzed as tertile, and
      performance on the Modified Mini-Mental State Examination (3MS) and Digit Symbol
      Substitution Test (DSST) at baseline and repeatedly over 9 years. Incident
      cognitive impairment (a decline of >1.0 SD on each test) was analyzed with
      logistic regression. RESULTS: Older adults with high pentosidine level had worse
      baseline DSST score (p=0.05) but not different 3MS score (p=0.32). On both tests,
      there was a more pronounced 9-year decline in those with high and mid pentosidine
      level compared to those in the lowest tertile (3MS 7.0, 5.4, and 2.5 point
      decline, p overall <0.001; DSST 5.9, 7.4, and 4.5 point decline, p=0.03).
      Incident cognitive impairment was higher in those with high or mid pentosidine
      level than those in the lowest tertile (3MS: 24% vs 17%, odds ratio=1.55; 95%
      confidence interval 1.07-2.26; DSST: 31% vs 22%, odds ratio=1.62; 95% confidence
      interval 1.13-2.33). There was no interaction between pentosidine level, diabetes
      status, and cognitive decline. Multivariate adjustment for age, sex, race,
      education, hypertension, cardiovascular disease, estimated glomerular filtration
      rate, and diabetes diminished results somewhat but overall patterns remained
      similar. CONCLUSION: High peripheral AGE level is associated with greater
      cognitive decline in older adults with and without diabetes.

PMID- 21900629
TI  - Prognostication after cardiac arrest: a tale of timing, confounders, and self
      fulfillment.

PMID- 21900630
TI  - Recurrent stroke-like episodes in X-linked Charcot-Marie-Tooth disease.

PMID- 21900631
TI  - A randomized trial of hypothesis-driven vs screening neurologic examination.
AB  - OBJECTIVE: We hypothesized that trainees would perform better using a hypothesis
      driven rather than a traditional screening approach to the neurologic
      examination. METHODS: We randomly assigned 16 medical students to perform
      screening examinations of all major aspects of neurologic function or hypothesis
      driven examinations focused on aspects suggested by the history. Each student
      examined 4 patients, 2 of whom had focal deficits. Outcomes of interest were the
      correct identification of patients with focal deficits, number of specific
      deficits detected, and examination duration. Outcomes were assessed by an
      investigator blinded to group assignments. The McNemar test was used to compare
      the sensitivity and specificity of the 2 examination methods. RESULTS:
      Sensitivity was higher with hypothesis-driven examinations than with screening
      examinations (78% vs 56%; p = 0.046), although specificity was lower (71% vs
      100%; p = 0.046). The hypothesis-driven group identified 61% of specific
      examination abnormalities, whereas the screening group identified 53% (p =
      0.008). Median examination duration was 1 minute shorter in the hypothesis-driven
      group (7.0 minutes vs 8.0 minutes; p = 0.13). CONCLUSIONS: In this randomized
      trial comparing 2 methods of neurologic examination, a hypothesis-driven approach
      resulted in greater sensitivity and a trend toward faster examinations, at the
      cost of lower specificity, compared with the traditional screening approach. Our
      findings suggest that a hypothesis-driven approach may be superior when the
      history is concerning for an acute focal neurologic process.

PMID- 21900632
TI  - Differential features of carotid and vertebral artery dissections: the CADISP
      study.
AB  - OBJECTIVE: To examine whether risk factor profile, baseline features, and outcome
      of cervical artery dissection (CEAD) differ according to the dissection site.
      METHODS: We analyzed 982 consecutive patients with CEAD included in the Cervical
      Artery Dissection and Ischemic Stroke Patients observational study (n = 619 with
      internal carotid artery dissection [ICAD], n = 327 with vertebral artery
      dissection [VAD], n = 36 with ICAD and VAD). RESULTS: Patients with ICAD were
      older (p < 0.0001), more often men (p = 0.006), more frequently had a recent
      infection (odds ratio [OR] = 1.59 [95% confidence interval (CI) 1.09-2.31]), and
      tended to report less often a minor neck trauma in the previous month (OR = 0.75
      [0.56-1.007]) compared to patients with VAD. Clinically, patients with ICAD more
      often presented with headache at admission (OR = 1.36 [1.01-1.84]) but less
      frequently complained of cervical pain (OR = 0.36 [0.27-0.48]) or had cerebral
      ischemia (OR = 0.32 [0.21-0.49]) than patients with VAD. Among patients with CEAD
      who sustained an ischemic stroke, the NIH Stroke Scale (NIHSS) score at admission
      was higher in patients with ICAD than patients with VAD (OR = 1.17 [1.12-1.22]).
      Aneurysmal dilatation was more common (OR = 1.80 [1.13-2.87]) and bilateral
      dissection less frequent (OR = 0.63 [0.42-0.95]) in patients with ICAD. Multiple
      concomitant dissections tended to cluster on the same artery type rather than
      involving both a vertebral and carotid artery. Patients with ICAD had a less
      favorable 3-month functional outcome (modified Rankin Scale score >2, OR = 3.99
      [2.32-6.88]), but this was no longer significant after adjusting for baseline
      NIHSS score. CONCLUSION: In the largest published series of patients with CEAD,
      we observed significant differences between VAD and ICAD in terms of risk
      factors, baseline features, and functional outcome.

PMID- 21900633
TI  - Does therapeutic hypothermia affect time to awakening in cardiac arrest
      survivors?
AB  - OBJECTIVE: Current guidelines indicate that certain clinical examination findings
      at 72 hours after cardiac arrest may be useful in prognosis. Some have suggested
      that hypothermia may alter the examination. We aimed to examine timing of
      awakening in cardiac arrest survivors treated with hypothermia. METHODS: A
      retrospective review of prospectively identified cardiac arrest survivors from
      June 2006 to December 2010 at a large academic institution. Data including time
      to awakening, prognostic variables, systemic complications, cause of mortality,
      reasons, and timing to withdrawal of life-sustaining treatments were recorded.
      Outcome measure of in-hospital mortality was assessed. RESULTS: A total of 227
      patients were included. In-hospital mortality was 53%. Of 128 treated with
      induced hypothermia, 64% survived. Of 99 patients not treated with hypothermia,
      24% survived. Median day of awakening was day 2 for both groups and most (91%
      hypothermic and 79% nonhypothermic) awakened within 3 days. In the hypothermic
      group, withdrawal of life-sustaining treatments preceded death in 41 patients;
      the decision was based primarily on poor neurologic prognosis in 29. The average
      day of death was 5 (range 3-11). In the nonhypothermic group, withdrawal of life
      sustaining treatments took place in 69 patients, of which 55 were based on poor
      neurologic prognosis. CONCLUSIONS: Awakening after therapeutic hypothermia is
      usually evident within 3 days of cardiac arrest and not delayed compared with
      nonhypothermia cases. Mortality in the hypothermia group was not uncommonly
      preceded by consequences of critical systemic illness.

PMID- 21900634
TI  - Advanced glycation end products, diabetes, and the brain.

PMID- 21900635
TI  - Stamping out neurophobia: a new hypothesis?

PMID- 21900637
TI  - Genetic analysis of aquaporin-4 in neuromyelitis optica.
AB  - OBJECTIVE: Autoantibodies to aquaporin-4 (AQP4) are specific and pathogenic for
      neuromyelitis optica (NMO). Therefore, we evaluated whether AQP4 single
      nucleotide polymorphisms (SNPs) are associated with susceptibility to NMO or
      whether mutations that potentially alter AQP4 structure or expression are present
      in some patients. METHODS: We genotyped 8 AQP4 SNPs chosen based on their minor
      allele frequency, location, and novelty in 177 NMO sporadic cases, 14 NMO
      familial cases, and 1,363 matched controls by TaqMan-based assay. We performed
      bidirectional sequencing of the promoter (1 kb), exons 0-4, and flanking splice
      consensus sequences, and the 5' and 3' untranslated regions of 177 sporadic and
      14 familial NMO cases. RESULTS: One of 8 SNPs (minor allele frequency = 0.01) was
      associated with NMO (NC 18.8; chrom pos. 22695167: T>A): odds ratio (95%
      confidence interval) = 13.1 (1.4-126.7); p = 0.026. In 3 patients with NMO (2
      related), we detected 2 different missense allelic mutations at Arg19 (R19I and
      R19T). None of the 1,363 control subjects had Arg19 mutations (p = 0.001).
      CONCLUSIONS: Except for one uncommon SNP, no tested SNP was associated with NMO,
      nor were 3 SNP haplotypes, providing no support for the hypothesis that genetic
      variation in AQP4 accounts for overall susceptibility to NMO. Two different
      allelic Arg19 missense mutations are specific to NMO and segregated with the
      disease in one pedigree. Although the pathobiology underlying this is not yet
      established, their effects on the structure of the M1 isoform N terminus or the
      regulatory sequence of the M23 isoform by virtue of their location support a role
      of AQP4 orthogonal array formation on molecular susceptibility to NMO.

PMID- 21900636
TI  - Minocycline treatment for HIV-associated cognitive impairment: results from a
      randomized trial.
AB  - OBJECTIVE: We conducted a study of minocycline to assess its safety,
      tolerability, and efficacy for the treatment of HIV-associated cognitive
      impairment. METHODS: HIV-1-infected individuals with progressive neurocognitive
      decline were enrolled in a double-blind, placebo-controlled study of minocycline.
      Participants were randomized to receive minocycline 100 mg or matching placebo
      orally every 12 hours. The primary efficacy measure was change in a
      neuropsychological test composite z score (NPZ-8) from baseline to week 24.
      Measures of safety included the frequency of adverse events and changes over time
      in laboratory tests. After 50% of participants completed the double-blind phase,
      an interim analysis of futility for the primary outcome measure was performed,
      and our Data and Safety Monitoring Board recommended early study termination.
      RESULTS: A total of 107 HIV-1-infected individuals with cognitive impairment were
      enrolled. The minocycline group did not show improvement in the primary outcome
      measure (NPZ-8) (mean 24-week change = 0.12) compared to placebo (mean 24-week
      change = 0.17) (95% confidence interval = [-0.26, 0.39], p = 0.70). There were
      few severe adverse events or laboratory abnormalities in either treatment group.
      CONCLUSION: Minocycline was safe and well-tolerated in individuals with HIV
      associated cognitive impairment, but cognitive improvement was not observed.
      Classification of evidence. This interventional study provides Class II evidence
      for the safety, tolerability, and efficacy of minocycline for the treatment of
      HIV-associated cognitive impairment.

PMID- 21900640
TI  - Low-magnitude whole body vibration with resistive exercise as a countermeasure
      against cardiovascular deconditioning after 60 days of head-down bed rest.
AB  - Whole body vibration with resistive exercise is a promising countermeasure
      against some weightlessness-induced dysfunctions. Our objective was to study
      whether the combination of low-magnitude whole body vibration with a resistive
      exercise can prevent the cardiovascular deconditioning induced by a nonstrict 60
      day head-down bed rest (Earth Star International Bed Rest Experiment Project).
      Fourteen healthy men participated in this study. We recorded electrocardiograms
      and blood pressure waves by means of a noninvasive beat-by-beat measurement
      system (Cardiospace, integrated by Centre National d'Etudes Spatiales and
      Astronaut Center of China) during an orthostatic test (20 min of 75-degree head
      up tilt test) before and immediately after bed rest. We estimated heart rate,
      blood pressure, cardiac output, stroke volume, total peripheral resistance,
      baroreflex sensitivity, and heart rate variability. Low-magnitude whole body
      vibration with resistive exercise prevented an increase of the sympathetic index
      (reflecting the sympathovagal balance of cardiac autonomic control) and limited
      the decrease of the spontaneous baroreflex sensitivity induced by 60 days of head
      down bed rest. However, this countermeasure had very little effect on cardiac
      hemodynamics and did not improve the orthostatic tolerance. This combined
      countermeasure did not efficiently prevent orthostatic intolerance but prevents
      changes in the autonomic nervous system associated with cardiovascular
      deconditioning. The underlying mechanisms remain hypothetical but might involve
      cutaneous and muscular mechanoreceptors.

PMID- 21900639
TI  - Sepsis-induced alterations in sleep of rats.
AB  - Sepsis is a systemic immune response to infection that may result in multiple
      organ failure and death. Polymicrobial infections remain a serious clinical
      problem, and in the hospital, sepsis is the number-one noncardiac killer.
      Although the central nervous system may be one of the first systems affected,
      relatively little effort has been made to determine the impact of sepsis on the
      brain. In this study, we used the cecal ligation and puncture (CLP) model to
      determine the extent to which sepsis alters sleep, the EEG, and brain temperature
      (Tbr) of rats. Sepsis increases the amount of time rats spend in non-rapid eye
      movement sleep (NREMS) during the dark period, but not during the light period.
      Rapid eye movements sleep (REMS) of septic rats is suppressed for about 24 h
      following CLP surgery, after which REMS increases during dark periods for at
      least three nights. The EEG is dramatically altered shortly after sepsis
      induction, as evidenced by reductions in slow-frequency components. Furthermore,
      sleep is fragmented, indicating that the quality of sleep is diminished. Effects
      on sleep, the EEG, and Tbr persist for at least 84 h after sepsis induction, the
      duration of our recording period. Immunohistochemical assays focused on brain
      stem mechanisms responsible for alterations in REMS, as little information is
      available concerning infection-induced suppression of this sleep stage. Our
      immunohistochemical data suggest that REMS suppression after sepsis onset may be
      mediated, in part, by the brain stem GABAergic system. This study demonstrates
      for the first time that sleep and EEG patterns are altered during CLP-induced
      sepsis. These data suggest that the EEG may serve as a biomarker for sepsis
      onset. These data also contribute to our knowledge of potential mechanisms,
      whereby infections alter sleep and other central nervous system functions.

PMID- 21900641
TI  - Central stiffening in adulthood linked to aberrant aortic remodeling under
      suboptimal intrauterine conditions.
AB  - This study examined perturbed aortic development and subsequent wall stiffening
      as a link to later cardiovascular disease. Placental insufficiency was induced in
      pregnant guinea pigs at midgestation by uterine artery ligation. Near term,
      fetuses were killed and defined as normal birth weight (NBW), low birth weight
      (LBW), and intrauterine growth restricted (IUGR). Offspring were classified
      according to birth weight and killed in adulthood. Collagen and elastin content
      of aortas were analyzed using Sirius red and orcein staining, respectively.
      Immunofluorescence was used for detection of alpha-actin and nonmuscle myosin
      heavy chain (MHC-B), a marker of synthetic-type vascular smooth muscle cells
      (VSMCs). Ex vivo generation of length-tension curves was performed with aortic
      rings from adult offspring. Relative elastic fiber content was decreased by 10%
      in LBW and 14% in IUGR compared with NBW fetuses. In adulthood, relative elastic
      fiber content was 51% lower in LBW vs. NBW, and the number of elastic laminae
      adjusted for wall thickness was 25% lower in LBW (P < 0.01). The percent area
      stained for MHC-B was sixfold higher in LBW vs. NBW fetuses (P < 0.0001) and
      threefold higher in LBW vs. NBW adult offspring (P < 0.05). The increase in MHC-B
      in LBW offspring concurred with a 41% increase in total collagen content and a 33
      and 56% increase in relative and total alpha-actin content, respectively (P <
      0.05). Thus aortic wall stiffening in adulthood can be traced to altered matrix
      composition established under suboptimal intrauterine conditions that is
      amplified postnatally by the activity of synthetic VSMCs.

PMID- 21900638
TI  - Secondary preventive medication persistence and adherence 1 year after stroke.
AB  - OBJECTIVE: Data on long-term use of secondary prevention medications following
      stroke are limited. The Adherence eValuation After Ischemic stroke-Longitudinal
      (AVAIL) Registry assessed patient, provider, and system-level factors influencing
      continuation of prevention medications for 1 year following stroke
      hospitalization discharge. METHODS: Patients with ischemic stroke or TIA
      discharged from 106 hospitals participating in the American Heart Association Get
      With The Guidelines-Stroke program were surveyed to determine their use of
      warfarin, antiplatelet, antihypertensive, lipid-lowering, and diabetes
      medications from discharge to 12 months. Reasons for stopping medications were
      ascertained. Persistence was defined as continuation of all secondary preventive
      medications prescribed at hospital discharge, and adherence as continuation of
      prescribed medications except those stopped according to health care provider
      instructions. RESULTS: Of the 2,880 patients enrolled in AVAIL, 88.4% (2,457
      patients) completed 1-year interviews. Of these, 65.9% were regimen persistent
      and 86.6% were regimen adherent. Independent predictors of 1-year medication
      persistence included fewer medications prescribed at discharge, having an
      adequate income, having an appointment with a primary care provider, and greater
      understanding of why medications were prescribed and their side effects.
      Independent predictors of adherence were similar to those for persistence.
      CONCLUSIONS: Although up to one-third of stroke patients discontinued one or more
      secondary prevention medications within 1 year of hospital discharge, self
      discontinuation of these medications is uncommon. Several potentially modifiable
      patient, provider, and system-level factors associated with persistence and
      adherence may be targets for future interventions.

PMID- 21900642
TI  - Central circuitries for body temperature regulation and fever.
AB  - Body temperature regulation is a fundamental homeostatic function that is
      governed by the central nervous system in homeothermic animals, including humans.
      The central thermoregulatory system also functions for host defense from invading
      pathogens by elevating body core temperature, a response known as fever.
      Thermoregulation and fever involve a variety of involuntary effector responses,
      and this review summarizes the current understandings of the central circuitry
      mechanisms that underlie nonshivering thermogenesis in brown adipose tissue,
      shivering thermogenesis in skeletal muscles, thermoregulatory cardiac regulation,
      heat-loss regulation through cutaneous vasomotion, and ACTH release. To defend
      thermal homeostasis from environmental thermal challenges, feedforward
      thermosensory information on environmental temperature sensed by skin
      thermoreceptors ascends through the spinal cord and lateral parabrachial nucleus
      to the preoptic area (POA). The POA also receives feedback signals from local
      thermosensitive neurons, as well as pyrogenic signals of prostaglandin E(2)
      produced in response to infection. These afferent signals are integrated and
      affect the activity of GABAergic inhibitory projection neurons descending from
      the POA to the dorsomedial hypothalamus (DMH) or to the rostral medullary raphe
      region (rMR). Attenuation of the descending inhibition by cooling or pyrogenic
      signals leads to disinhibition of thermogenic neurons in the DMH and sympathetic
      and somatic premotor neurons in the rMR, which then drive spinal motor output
      mechanisms to elicit thermogenesis, tachycardia, and cutaneous vasoconstriction.
      Warming signals enhance the descending inhibition from the POA to inhibit the
      motor outputs, resulting in cutaneous vasodilation and inhibited thermogenesis.
      This central thermoregulatory mechanism also functions for metabolic regulation
      and stress-induced hyperthermia.

PMID- 21900643
TI  - Recovery of baroreflex control of renal sympathetic nerve activity after spinal
      lesions in the rat.
AB  - Spinal cord injury (SCI) has serious long-term consequences on sympathetic
      cardiovascular regulation. Orthostatic intolerance results from insufficient
      baroreflex regulation (BR) of sympathetic outflow to maintain proper blood
      pressure upon postural changes. Autonomic dysreflexia occurs due to insufficient
      inhibition of spinal sources of sympathetic activity. Both of these conditions
      result from the inability to control sympathetic activity caudal to SCI. It is
      well established that limited motor ability recovers after incomplete SCI.
      Therefore, the goal of this study was to determine whether recovery of BR occurs
      after chronic, left thoracic spinal cord hemisection at either T(3) or T(8).
      Baroreflex tests were performed in rats by measuring the reflex response of left
      (ipsilateral) renal sympathetic nerve activity to decreases and increases in
      arterial pressure produced by ramped infusions of sodium nitroprusside and
      phenylephrine, respectively. One week after a T(3) left hemisection, BR function
      was modestly impaired. However, 8 wk after a T(3) left hemisection, BR function
      was normal. One week after a T(8) left hemisection, BR function was significantly
      impaired, and 8 wk after a T(8) left hemisection, BR function was significantly
      improved. These results indicate that BR of renal sympathetic nerve activity in
      rats may partially recover after spinal cord hemisections, becoming normal by 8
      wk after a T(3) lesion, but not after a T(8) lesion. The nature of the spinal
      cord and/or brain stem reorganization that mediates this recovery remains to be
      determined.

PMID- 21900646
TI  - Enhanced open-loop but not closed-loop cardiac baroreflex sensitivity during
      orthostatic stress in humans.
AB  - The neural interaction between the cardiopulmonary and arterial baroreflex may be
      critical for the regulation of blood pressure during orthostatic stress. However,
      studies have reported conflicting results: some indicate increases and others
      decreases in cardiac baroreflex sensitivity (i.e., gain) with cardiopulmonary
      unloading. Thus the effect of orthostatic stress-induced central hypovolemia on
      regulation of heart rate via the arterial baroreflex remains unclear. We sought
      to comprehensively assess baroreflex function during orthostatic stress by
      identifying and comparing open- and closed-loop dynamic cardiac baroreflex gains
      at supine rest and during 60 degrees  head-up tilt (HUT) in 10 healthy men.
      Closed-loop dynamic "spontaneous" cardiac baroreflex sensitivities were
      calculated by the sequence technique and transfer function and compared with two
      open-loop carotid-cardiac baroreflex measures using the neck chamber system: 1) a
      binary white-noise method and 2) a rapid-pulse neck pressure-neck suction
      technique. The gain from the sequence technique was decreased from -1.19 +/- 0.14
      beats.min(-1).mmHg(-1) at rest to -0.78 +/- 0.10 beats.min(-1).mmHg(-1) during
      HUT (P = 0.005). Similarly, closed-loop low-frequency baroreflex transfer
      function gain was reduced during HUT (P = 0.033). In contrast, open-loop low
      frequency transfer function gain between estimated carotid sinus pressure and
      heart rate during white-noise stimulation was augmented during HUT (P = 0.01).
      This result was consistent with the maximal gain of the carotid-cardiac
      baroreflex stimulus-response curve (from 0.47 +/- 0.15 beats.min(-1).mmHg(-1) at
      rest to 0.60 +/- 0.20 beats.min(-1).mmHg(-1) at HUT, P = 0.037). These findings
      suggest that open-loop cardiac baroreflex gain was enhanced during HUT. Moreover,
      under closed-loop conditions, spontaneous baroreflex analyses without external
      stimulation may not represent open-loop cardiac baroreflex characteristics during
      orthostatic stress.

PMID- 21900644
TI  - Interactions between CD36 and global intestinal alkaline phosphatase in mouse
      small intestine and effects of high-fat diet.
AB  - The mechanisms of the saturable component of long-chain fatty acid (LCFA)
      transport across the small intestinal epithelium and its regulation by a high-fat
      diet (HFD) are uncertain. It is hypothesized here that the putative fatty acid
      translocase/CD36 and intestinal alkaline phosphatases (IAPs) function together to
      optimize LCFA transport. Phosphorylated CD36 (pCD36) was expressed in mouse
      enterocytes and dephosphorylated by calf IAP (CIAP). Uptake of fluorescently
      tagged LCFA into isolated enteroctyes was increased when cells were treated with
      CIAP; this was blocked with a specific CD36 inhibitor. pCD36 colocalized in
      enterocytes with the global IAP (gIAP) isozyme and, specifically,
      coimmunoprecipitated with gIAP, but not the duodenal-specific isozyme (dIAP).
      Purified recombinant gIAP dephosphorylated immunoprecipitated pCD36, and
      antiserum to gIAP decreased initial LCFA uptake in enterocytes. Body weight,
      adiposity, and plasma leptin and triglycerides were significantly increased in
      HFD mice compared with controls fed a normal-fat diet. HFD significantly
      increased immunoreactive CD36 and gIAP, but not dIAP, in jejunum, but not
      duodenum. Uptake of LCFA was increased in a CD36-dependent manner in enterocytes
      from HFD mice. It is concluded that CD36 exists in its phosphorylated and
      dephosphorylated states in mouse enterocytes, that pCD36 is a substrate of gIAP,
      and that dephosphorylation by IAPs results in increased LCFA transport
      capability. HFD upregulates CD36 and gIAP in parallel and enhances CD36-dependent
      fatty acid uptake. The interactions between these proteins may be important for
      efficient fat transport in mouse intestine, but whether the changes in gIAP and
      CD36 in enterocytes contribute to HFD-induced obesity remains to be determined.

PMID- 21900647
TI  - Distension of the uterus induces HspB1 expression in rat uterine smooth muscle.
AB  - The uterine musculature, or myometrium, demonstrates tremendous plasticity during
      pregnancy under the influences of the endocrine environment and mechanical
      stresses. Expression of the small stress protein heat shock protein B1 (HspB1)
      has been reported to increase dramatically during late pregnancy, a period marked
      by myometrial hypertrophy caused by fetal growth-induced uterine distension.
      Thus, using unilaterally pregnant rat models and ovariectomized nonpregnant rats
      with uteri containing laminaria tents to induce uterine distension, we examined
      the effect of uterine distension on myometrial HspB1 expression. In unilaterally
      pregnant rats, HspB1 mRNA and Ser(15)-phosphorylated HspB1 (pSer(15) HspB1)
      protein expression were significantly elevated in distended gravid uterine horns
      at days 19 and 23 (labor) of gestation compared with nongravid horns. Similarly,
      pSer(15) HspB1 protein in situ was only readily detectable in the distended horns
      compared with the nongravid horns at days 19 and 23; however, pSer(15) HspB1 was
      primarily detectable in situ at day 19 in membrane-associated regions, while it
      had primarily a cytoplasmic localization in myometrial cells at day 23. HspB1
      mRNA and pSer(15) HspB1 protein expression were also markedly increased in
      ovariectomized nonpregnant rat myometrium distended for 24 h with laminaria tents
      compared with empty horns. Therefore, uterine distension plays a major role in
      the stimulation of myometrial HspB1 expression, and increased expression of this
      small stress protein could be a mechanoadaptive response to the increasing
      uterine distension that occurs during pregnancy.

PMID- 21900645
TI  - Blood pressure and renal hemodynamic responses to acute angiotensin II infusion
      are enhanced in a female mouse model of systemic lupus erythematosus.
AB  - Inflammation and immune system dysfunction contributes to the development of
      cardiovascular and renal disease. Systemic lupus erythematosus (SLE) is a chronic
      autoimmune inflammatory disorder that carries a high risk for both renal and
      cardiovascular disease. While hemodynamic changes that may contribute to
      increased cardiovascular risk have been reported in humans and animal models of
      SLE, renal hemodynamics have not been widely studied. The renin-angiotensin
      system (RAS) plays a central role in renal hemodynamic control, and although RAS
      blockade is a common therapeutic strategy, the role of RAS in hemodynamic
      function during SLE is not clear. This study tested whether mean arterial
      pressure (MAP) and renal hemodynamic responses to acute infusions of ANG II in
      anesthetized animals were enhanced in an established female mouse model of SLE
      (NZBWF1). Baseline MAP was not different between anesthetized SLE and control
      (NZWLacJ) mice, while renal blood flow (RBF) was significantly lower in mice with
      SLE. SLE mice exhibited an enhanced pressor response and greater reduction in RBF
      after ANG II infusion. An acute infusion of the ANG II receptor blocker losartan
      increased RBF in control mice but not in mice with SLE. Renin and ANG II type 1
      receptor expression was significantly lower, and ANG II type 2 receptor
      expression was increased in the renal cortex from SLE mice compared with
      controls. These data suggest that there are fewer ANG II receptors in the kidneys
      from mice with SLE but that the existing receptors exhibit an enhanced
      sensitivity to ANG II.

PMID- 21900648
TI  - Skeletal muscle weakness due to deficiency of CuZn-superoxide dismutase is
      associated with loss of functional innervation.
AB  - An association between oxidative stress and muscle atrophy and weakness in vivo
      is supported by elevated oxidative damage and accelerated loss of muscle mass and
      force with aging in CuZn-superoxide dismutase-deficient (Sod1(-/-)) mice. The
      purpose was to determine the basis for low specific force (N/cm(2)) of
      gastrocnemius muscles in Sod1(-/-) mice and establish the extent to which
      structural and functional changes in muscles of Sod1(-/-) mice resemble those
      associated with normal aging. We tested the hypothesis that muscle weakness in
      Sod1(-/-) mice is due to functionally denervated fibers by comparing forces
      during nerve and direct muscle stimulation. No differences were observed for wild
      type mice at any age in the forces generated in response to nerve and muscle
      stimulation. Nerve- and muscle-stimulated forces were also not different for 4-wk
      old Sod1(-/-) mice, whereas, for 8- and 20-mo-old mice, forces during muscle
      stimulation were 16 and 30% greater, respectively, than those obtained using
      nerve stimulation. In addition to functional evidence of denervation with aging,
      fiber number was not different for Sod1(-/-) and wild-type mice at 4 wk, but 50%
      lower for Sod1(-/-) mice by 20 mo, and denervated motor end plates were prevalent
      in Sod1(-/-) mice at both 8 and 20 mo and in WT mice by 28 mo. The data suggest
      ongoing denervation in muscles of Sod1(-/-) mice that results in fiber loss and
      muscle atrophy. Moreover, the findings support using Sod1(-/-) mice to explore
      mechanistic links between oxidative stress and the progression of deficits in
      muscle structure and function.

PMID- 21900650
TI  - Urgent measures for an old problem.

PMID- 21900649
TI  - Phylogenomic analysis resolves the interordinal relationships and rapid
      diversification of the laurasiatherian mammals.
AB  - Although great progress has been made in resolving the relationships of placental
      mammals, the position of several clades in Laurasiatheria remain controversial.
      In this study, we performed a phylogenetic analysis of 97 orthologs (46,152 bp)
      for 15 taxa, representing all laurasiatherian orders. Additionally, phylogenetic
      trees of laurasiatherian mammals with draft genome sequences were reconstructed
      based on 1608 exons (2,175,102 bp). Our reconstructions resolve the interordinal
      relationships within Laurasiatheria and corroborate the clades Scrotifera,
      Fereuungulata, and Cetartiodactyla. Furthermore, we tested alternative topologies
      within Laurasiatheria, and among alternatives for the phylogenetic position of
      Perissodactyla, a sister-group relationship with Cetartiodactyla receives the
      highest support. Thus, Pegasoferae (Perissodactyla + Carnivora + Pholidota +
      Chiroptera) does not appear to be a natural group. Divergence time estimates from
      these genes were compared with published estimates for splits within
      Laurasiatheria. Our estimates were similar to those of several studies and
      suggest that the divergences among these orders occurred within just a few
      million years.

PMID- 21900651
TI  - Desperately seeking savings: states shift more Medicaid enrollees to managed
      care.

PMID- 21900652
TI  - A decade of health care cost growth has wiped out real income gains for an
      average US family.
AB  - Although a median-income US family of four with employer-based health insurance
      saw its gross annual income increase from $76,000 in 1999 to $99,000 in 2009 (in
      current dollars), this gain was largely offset by increased spending to pay for
      health care. Monthly spending increases occurred in the family's health insurance
      premiums (from $490 to $1,115), out-of-pocket health spending (from $135 to
      $235), and taxes devoted to health care (from $345 to $440). After accounting for
      price increases in other goods and services, the family had $95 more in monthly
      income to devote to nonhealth spending in 2009 than in 1999. By contrast, had the
      rate of health care cost growth not exceeded general inflation, the family would
      have had $545 more per month instead of $95-a difference of nearly $5,400 per
      year. Even the $95 gain was artificial, because tax collections in 2009 were
      insufficient to cover actual increases in federal health spending. As a result,
      we argue, the burdens imposed on all payers by steadily rising health care
      spending can no longer be ignored.

PMID- 21900653
TI  - Lower-income families pay a higher share of income toward national health care
      spending than higher-income families do.
AB  - All health care spending from public and private sources, such as governments and
      businesses, is ultimately paid by individuals and families. We calculated the
      burden of US health care spending on families as a percentage of income and found
      that at the national level, lower-income families pay a larger share of their
      incomes toward health care than do higher-income families. Specifically, we found
      that payments made privately, such as those for health insurance or out-of-pocket
      spending for care, and publicly, through taxes and tax expenditures, consumed
      more than 20 percent of family income for families in the lowest-income quintile
      but no more than 16 percent for families in any other income quintile. Our
      analysis provides a framework for considering the equity of various initiatives
      under health reform. Although many effects remain to be seen, we find that,
      overall, the Affordable Care Act should reduce inequities in the burden of paying
      for national health care spending.

PMID- 21900654
TI  - Higher fees paid to US physicians drive higher spending for physician services
      compared to other countries.
AB  - Higher health care prices in the United States are a key reason that the nation's
      health spending is so much higher than that of other countries. Our study
      compared physicians' fees paid by public and private payers for primary care
      office visits and hip replacements in Australia, Canada, France, Germany, the
      United Kingdom, and the United States. We also compared physicians' incomes net
      of practice expenses, differences in financing the cost of medical education, and
      the relative contribution of payments per physician and of physician supply in
      the countries' national spending on physician services. Public and private payers
      paid somewhat higher fees to US primary care physicians for office visits (27
      percent more for public, 70 percent more for private) and much higher fees to
      orthopedic physicians for hip replacements (70 percent more for public, 120
      percent more for private) than public and private payers paid these physicians'
      counterparts in other countries. US primary care and orthopedic physicians also
      earned higher incomes ($186,582 and $442,450, respectively) than their foreign
      counterparts. We conclude that the higher fees, rather than factors such as
      higher practice costs, volume of services, or tuition expenses, were the main
      drivers of higher US spending, particularly in orthopedics.

PMID- 21900655
TI  - The growth in cost per case explains far more of US health spending increases
      than rising disease prevalence.
AB  - Some prior research has suggested that health spending for many diseases has been
      driven more by increases in so-called treated prevalence-the number of people
      receiving treatment for a given condition-than by increases in cost per case. Our
      study reached a different conclusion. We examined treated prevalence, clinical
      prevalence-the number of people with a given disease, treated or not-and cost per
      case across all medical conditions between 1996 and 2006. Over this period, three
      fourths of the increase in real per capita health spending was attributable to
      growth in cost per case, while treated prevalence accounted for about one-fourth
      of spending growth. Our evidence suggests that most of the treated-prevalence
      effect is due to an increase in the share of eligible people being treated rather
      than an increase in clinical prevalence of diseases. We conclude that efforts to
      curb health spending should focus more on reining in cost per case.

PMID- 21900656
TI  - Health care costs are a key driver of growth in federal and state assistance to
      working-age people with disabilities.
AB  - A large and rapidly growing share of US government expenditures pays for
      assistance to working-age people with disabilities. In 2008 federal spending for
      disability assistance totaled $357 billion, representing 12 percent of all
      federal outlays. The states' share of joint federal-state disability programs,
      more than 90 percent of it for Medicaid, was $71 billion. The increased cost of
      health care-which represented 55 percent of combined state and federal outlays
      for this population in 2008-is one of the two main causes of spending growth for
      people with disabilities. Health care is already likely to be a target of further
      efforts by states and the federal government to contain or reduce spending, and
      it is therefore probable that spending restraints will affect the working-age
      population with disabilities. In fact, unless ways can be identified to make
      delivery of health care to this population more efficient, policy makers may be
      unable to avoid funding cuts that will further compromise its well-being.

PMID- 21900657
TI  - Enrolling people with prediabetes ages 60-64 in a proven weight loss program
      could save Medicare $7 billion or more.
AB  - Rising chronic disease prevalence among Medicare beneficiaries, including new
      enrollees, is a key driver of health care spending. Randomized trials have shown
      that lifestyle modification interventions such as those in the National Diabetes
      Prevention Program clinical trial reduce the incidence of chronic disease and
      that community-based programs applying the same principles can produce net health
      care savings. We propose expanding a proven, community-based weight loss program
      nationwide and enrolling overweight and obese prediabetic adults ages 60-64. We
      estimate that making the program available to a single cohort of eligible people
      could save Medicare $1.8-$2.3 billion over the following ten years. Estimated
      savings would be even higher ($3.0-$3.7 billion) if equally overweight people at
      risk for cardiovascular disease were also enrolled. We estimate that lifetime
      Medicare savings could range from approximately $7 billion to $15 billion,
      depending on how broadly program eligibility was defined and actual levels of
      program participation, for a single "wave" of eligible people. In this context we
      propose that Medicare expand its new wellness benefit to include reimbursement
      for this and other qualifying behavior change programs.

PMID- 21900658
TI  - At Virginia Mason, collaboration among providers, employers, and health plans to
      transform care cut costs and improved quality.
AB  - Virginia Mason Medical Center in Seattle has worked in collaboration with health
      plans and employers to facilitate development of standardized approaches to care
      of patients with common conditions. These efforts have eliminated unnecessary
      treatment and decreased costs to employers, health plans, patients, and
      providers. We describe our collaborative approach and illustrate it with the
      example of improved treatment for patients with uncomplicated headache, for which
      we have achieved 91 percent patient satisfaction, decreased use of advanced
      imaging by 23 percent, and provided same-day appointments in 95 percent of cases.
      As a model for improving quality while reducing cost, the Virginia Mason
      experience demonstrates that a multispecialty group practice, hospital,
      employers, and health plans can define quality and align performance and payment
      along common goals.

PMID- 21900660
TI  - Integrated telehealth and care management program for Medicare beneficiaries with
      chronic disease linked to savings.
AB  - Treatment of chronically ill people constitutes nearly four-fifths of US health
      care spending, but it is hampered by a fragmented delivery system and
      discontinuities of care. We examined the impact of a care coordination approach
      called the Health Buddy Program, which integrates a telehealth tool with care
      management for chronically ill Medicare beneficiaries. We evaluated the program's
      impact on spending for patients of two clinics in the US Northwest who were
      exposed to the intervention, and we compared their experience with that of
      matched controls. We found significant savings among patients who used the Health
      Buddy telehealth program, which was associated with spending reductions of
      approximately 7.7-13.3 percent ($312-$542) per person per quarter. These results
      suggest that carefully designed and implemented care management and telehealth
      programs can help reduce health care spending and that such programs merit
      continued attention by Medicare. Meanwhile, mortality differences in the
      treatment and control groups suggest that the intervention may have produced
      noticeable changes in health outcomes, but we leave it to future research to
      explore these effects fully.

PMID- 21900661
TI  - Model safety-net programs could care for the uninsured at one-half the cost of
      Medicaid or private insurance.
AB  - Because the reforms under the Affordable Care Act of 2010 will leave an estimated
      twenty million or more people still uninsured, some Americans will continue to
      seek care at low or no cost through existing safety-net systems. To identify
      appropriate care models, this comparative case study assessed the costs of care
      provided by four large, well-structured, comprehensive safety-net programs for
      the uninsured in Colorado, Michigan, North Carolina, and Texas. The average
      monthly resource cost-including the value of referred, donated, and in-kind
      services-in these model programs was $141-$209 per adult in 2008. This was 25-50
      percent less than the estimated cost of care for comparison groups covered by
      local Medicaid programs or by private insurance that provided similar services.
      Although these programs' services are somewhat less comprehensive than those of
      generous insurance plans, the findings suggest that these model safety-net
      programs could be adapted to provide an alternative type of coverage for the
      uninsured, including both low-income and middle-class people.

PMID- 21900662
TI  - Medicare's bundled payment pilot for acute and postacute care: analysis and
      recommendations on where to begin.
AB  - In the National Pilot Program on Payment Bundling, a subset of Medicare providers
      will receive a single payment for an episode of acute care in a hospital,
      followed by postacute care in a skilled nursing or rehabilitation facility, the
      patient's home, or other appropriate setting. This article examines the promises
      and pitfalls of bundled payments and addresses two important design decisions for
      the pilot: which conditions to include, and how long an episode should be. Our
      analysis of Medicare data found that hip fracture and joint replacement are good
      conditions to include in the pilot because they exhibit strong potential for cost
      savings. In addition, these conditions pose less financial risk for providers
      than other common ones do, so including them would make participation in the
      program more appealing to providers. We also found that longer episode lengths
      captured a higher percentage of costs and hospital readmissions while adding
      little financial risk. We recommend that the Medicare pilot program test
      alternative design features to help foster payment innovation throughout the
      health system.

PMID- 21900663
TI  - Early lessons from accountable care models in the private sector: partnerships
      between health plans and providers.
AB  - New health care delivery and payment models in the private sector are being
      shaped by active collaboration between health insurance plans and providers. We
      examine key characteristics of several of these private accountable care models,
      including their overall efforts to improve the quality, efficiency, and
      accountability of care; their criteria for selecting providers; the payment
      methods and performance measures they are using; and the technical assistance
      they are supplying to participating providers. Our findings show that not all
      providers are equally ready to enter into these arrangements with health plans
      and therefore flexibility in design of these arrangements is critical. These
      findings also hold lessons for the emerging public accountable care models, such
      as the Medicare Shared Savings Program-underscoring providers' need for
      comprehensive and timely data and analytic reports; payment tailored to
      providers' readiness for these contracts; and measurement of quality across
      multiple years and care settings.

PMID- 21900664
TI  - The increased concentration of health plan markets can benefit consumers through
      lower hospital prices.
AB  - The long-term trend of consolidation among US health plans has raised providers'
      concerns that the concentration of health plan markets can depress their prices.
      Although our study confirmed that, it also revealed a more complex picture.
      First, we found that 64 percent of hospitals operate in markets where health
      plans are not very concentrated, and only 7 percent are in markets that are
      dominated by a few health plans. Second, we found that in most markets, hospital
      market concentration exceeds health plan concentration. Third, our study
      confirmed earlier studies showing that greater hospital market concentration
      leads to higher hospital prices. Fourth, we found that hospital prices in the
      most concentrated health plan markets are approximately 12 percent lower than in
      more competitive health plan markets. Overall, our results show that more
      concentrated health plan markets can counteract the price-increasing effects of
      concentrated hospital markets, and that-contrary to conventional wisdom-increased
      health plan concentration benefits consumers through lower hospital prices as
      long as health plan markets remain competitive. Our findings also suggest that
      consumers would benefit from policies that maintained competition in hospital
      markets or that would restore competition to hospital markets that are
      uncompetitive.

PMID- 21900665
TI  - Medical group responses to global payment: early lessons from the 'Alternative
      Quality Contract' in Massachusetts.
AB  - The largest insurer in Massachusetts, Blue Cross Blue Shield, began a new program
      in 2009 that combines global payments-fixed payments for the care of patient
      populations during a specified time period-with large potential quality bonuses
      for medical groups. In interviews with representatives of the participating
      medical groups, many of which could be considered prototype accountable care
      organizations, we found that most groups initially focused on two goals: building
      the infrastructure to help primary care providers earn quality bonuses; and
      managing referrals to direct patients to lower-cost settings. Groups are working
      to overcome numerous challenges, which include improving their data management
      capabilities; managing conflicting incentives in their fee-for-service contracts;
      and establishing cultures that emphasize teamwork, patient-centered care, and
      effective stewardship of medical resources. The participating medical groups are
      diverse in terms of size, organizational structure, and prior experience with
      managed care contracting. If the groups can succeed in reducing annual growth in
      health spending by half over the five-year contract, it could signal that even
      newly formed accountable care organizations can navigate a shift from fee-for
      service to population-based payment models.

PMID- 21900666
TI  - Urban hospital 'clusters' do shift high-risk procedures to key facilities, but
      more could be done.
AB  - Since the 1990s, rapid consolidation in the hospital sector has resulted in the
      vast majority of hospitals joining systems that already had a considerable
      presence within their markets. We refer to these important local and regional
      systems as "clusters." To determine whether hospital clusters have taken
      measurable steps aimed at improving the quality of care-specifically, by
      concentrating low-volume, high-complexity services within selected "lead"
      facilities-this study examined within-cluster concentrations of high-risk cases
      for seven surgical procedures. We found that lead hospitals on average performed
      fairly high percentages of the procedures per cluster, ranging from 59 percent
      for esophagectomy to 87 percent for aortic valve replacement. The numbers
      indicate that hospitals might need to work with rival facilities outside their
      cluster to concentrate cases for the lowest-volume procedures, such as
      esophagectomies, whereas coordination among cluster members might be sufficient
      for higher-volume procedures. The results imply that policy makers should focus
      on clusters' potential for restructuring care and further coordinating services
      across hospitals in local areas.

PMID- 21900667
TI  - Strict hand hygiene and other practices shortened stays and cut costs and
      mortality in a pediatric intensive care unit.
AB  - Efforts to reduce infections acquired during a hospital stay through improvements
      in the quality of care have had measurable results in many hospital settings. In
      pediatric intensive care units, the right quality interventions can save lives
      and money. We found that improving practices of hand hygiene, oral care, and
      central-line catheter care reduced hospital-acquired infections and improved
      mortality rates among children admitted to a large pediatric intensive care unit
      in 2007-09. In addition, on average patients admitted after the quality
      interventions were fully implemented spent 2.3 fewer days in the hospital, their
      hospitalization cost $12,136 less, and mortality was 2.3 percentage points lower,
      compared to patients admitted before the interventions. The projected annual cost
      savings for the single pediatric intensive care unit studied was approximately
      $12 million. Given the modest expenses incurred for these improvements-which
      mainly consisted of posters for an educational campaign, a training "fair,"
      roughly $21 per day for oral care kits, about $0.60 per day for chlorhexidine
      antiseptic patches, and hand sanitizers attached to the walls outside patients'
      rooms-this represents a significant return on investment. Used on a larger scale,
      these quality improvements could save lives and reduce costs for patients,
      hospitals, and payers around the country, provided that sustained efforts ensure
      compliance with new protocols and achieve long-lasting changes.

PMID- 21900668
TI  - Affordable Care Act reforms could reduce the number of underinsured US adults by
      70 percent.
AB  - To provide a baseline and assess the potential of changes brought about under the
      Affordable Care Act, this study estimates the number of US adults who were
      underinsured or uninsured in 2010. Using indicators of medical cost exposure
      relative to income, we find that 44 percent (81 million) of adults ages 19-64
      were either uninsured or underinsured in 2010-up from 75 million in 2007 and 61
      million in 2003. Adults with incomes below 250 percent of the federal poverty
      level account for sizable majorities of those at risk of becoming uninsured or
      underinsured. If reforms succeed in increasing the affordability of care for
      people in this income range, we could expect a 70 percent drop in the number of
      underinsured people and a steep drop in the number of uninsured people.

PMID- 21900669
TI  - An agenda for improving compassionate care: a survey shows about half of patients
      say such care is missing.
AB  - As the US health care system undergoes restructuring and pressure to reduce costs
      intensifies, patients worry that they will receive less compassionate care. So do
      health care providers. Our survey of 800 recently hospitalized patients and 510
      physicians found broad agreement that compassionate care is "very important" to
      successful medical treatment. However, only 53 percent of patients and 58 percent
      of physicians said that the health care system generally provides compassionate
      care. Given strong evidence that such care improves health outcomes and patients'
      care experiences, we recommend that national quality standards include measures
      of compassionate care; that such care be a priority for comparative effectiveness
      research to determine which aspects have the most influence on patients' care
      experiences, health outcomes, and perceptions of health-related quality of life;
      and that payers reward the provision of such care. We also recommend the
      development of systematic approaches to help health care professionals improve
      the skills required for compassionate care.

PMID- 21900670
TI  - Strong government influence over the Israeli health care system has led to low
      rates of spending growth.
AB  - Israel reformed its health care system in 1995. In contrast to many other
      developed nations, it has since experienced relatively low rates of growth in
      health spending, even as health outcomes have continued to improve. This paper
      describes characteristics of the Israeli system that have helped control rising
      costs. We describe how the national government exerts direct operational control
      over a large proportion of total health care expenditures (39.1 percent in 2007)
      through a range of mechanisms, including caps on hospital revenue and national
      contracts with salaried physicians. The Ministry of Finance has been able to
      persuade the national government to agree to relatively small increases in the
      health care budget because the system has performed well, with a very high level
      of public satisfaction. It is unclear whether this success in health expenditure
      control can be sustained because of growing signs of strain within the system,
      the rapid increase in nongovernment financing for health care services, and the
      growing prosperity of Israeli society.

PMID- 21900671
TI  - How a children's hospital discovered child pornographers in its midst.

PMID- 21900672
TI  - Foundation's consumer advocacy health reform initiative strengthened groups'
      effectiveness.
AB  - Private foundations may hesitate to fund consumer advocacy for enacting and
      implementing health reform because the effects are hard to measure, and because
      they are concerned that funds will be used for lobbying activities that are
      prohibited by federal tax rules governing private philanthropy. Mathematica
      Policy Research evaluated a Robert Wood Johnson Foundation initiative supporting
      state consumer health advocacy networks. During the three-year grant period, most
      networks coalesced and improved their ability to advocate effectively. A majority
      of state policy makers reported that consumers became more involved and effective
      in shaping health policy, and many wanted consumer advocates to remain involved
      in public debates on implementing federal health reform. The evaluation shows
      that targeted investments by foundations to strengthen consumer groups' ability
      to advocate effectively can help ensure that their voice is heard in critical
      policy debates.

PMID- 21900674
TI  - Turning smaller practices into patient-centered medical homes.

PMID- 21900675
TI  - Caring for patients and much more.

PMID- 21900677
TI  - Explanations for increased prescription drug abuse.

PMID- 21900678
TI  - Dissecting the phthalate-induced Sertoli cell injury: the fragile balance of
      proteases and their inhibitors.

PMID- 21900679
TI  - A homolog of the cell apoptosis susceptibility gene involved in ovary development
      of Chinese shrimp Fenneropenaeus chinensis.
AB  - The cell apoptosis susceptibility (CAS) gene is a homolog of the yeast chromosome
      segregation (CSE1) gene, which functions in cell proliferation and apoptosis. In
      the present study, a homolog of CAS was cloned from Chinese shrimp Fenneropenaeus
      chinensis (FcCAS). The full-length FcCAS cDNA is 3534 bp and contains an open
      reading frame encoding 968 amino acids. The predicted tertiary FcCAS structure is
      highly similar to that of CSE1 from the yeast Saccharomyces cerevisiae. RT-PCR
      analysis showed that the FcCAS gene is expressed mainly in testis, ovary,
      stomach, lymphoid organs, gills, and hemocytes. RNA in situ hybridization showed
      that FcCAS transcripts were distributed mainly in the cytoplasm of oocytes.
      Western blot analysis showed that FcCAS could be detected only in testis and
      ovary, and its expression levels differed at different developmental stages of
      ovaries. Immunohistochemical analysis showed that FcCAS existed in both the
      cytoplasm and the nucleus, which suggested that FcCAS might function as a nuclear
      protein. No transcript was detected in the abnormally developed ovaries of
      triploid shrimp. Therefore, we inferred that the FcCAS gene might be one of the
      key genes that is closely related to ovary development in shrimp.

PMID- 21900680
TI  - Loss of Wnt5a disrupts primordial germ cell migration and male sexual development
      in mice.
AB  - Disruptions in the regulatory pathways controlling sex determination and
      differentiation can cause disorders of sex development, often compromising
      reproductive function. Although extensive efforts have been channeled into
      elucidating the regulatory mechanisms controlling the many aspects of sexual
      differentiation, the majority of disorders of sex development phenotypes are
      still unexplained at the molecular level. In this study, we have analyzed the
      potential involvement of Wnt5a in sexual development and show in mice that Wnt5a
      is male-specifically upregulated within testicular interstitial cells at the
      onset of gonad differentiation. Homozygous deletion of Wnt5a affected sexual
      development in male mice, causing testicular hypoplasia and bilateral
      cryptorchidism despite the Leydig cells producing factors such as Hsd3b1 and
      Insl3. Additionally, Wnt5a-null embryos of both sexes showed a significant
      reduction in gonadal germ cell numbers, which was caused by aberrant primordial
      germ cell migration along the hindgut endoderm prior to gonadal colonization. Our
      results indicate multiple roles for Wnt5a during mammalian reproductive
      development and help to clarify further the etiology of Robinow syndrome (OMIM
      268310), a disease previously linked to the WNT5A pathway.

PMID- 21900681
TI  - Immunophenotype and cytokine profiles of rhesus monkey CD56bright and CD56dim
      decidual natural killer cells.
AB  - The primate endometrium is characterized in pregnancy by a tissue-specific
      population of CD56(bright) natural killer (NK) cells. These cells are observed in
      human, rhesus, and other nonhuman primate decidua. However, other subsets of NK
      cells are present in the decidua and may play distinct roles in pregnancy. The
      purpose of this study was to define the surface marker phenotype of rhesus monkey
      decidual NK (dNK) cell subsets, and to address functional differences by
      profiling cytokine and chemokine secretion in contrast with decidual T cells and
      macrophages. Rhesus monkey decidual leukocytes were obtained from early pregnancy
      tissues, and were characterized by flow cytometry and multiplex assay of secreted
      factors. We concluded that the major NK cell population in rhesus early pregnancy
      decidua are CD56(bright) CD16(+)NKp30(-) decidual NK cells, with minor CD56(dim)
      and CD56(neg) dNK cells. Intracellular cytokine staining demonstrated that
      CD56(dim) and not CD56(bright) dNK cells are the primary interferon-gamma (IFNG)
      producers. In addition, the profile of other cytokines, chemokines, and growth
      factors secreted by these two dNK cell populations was generally similar, but
      distinct from that of peripheral blood NK cells. Finally, analysis of multiple
      pregnancies from eight dams revealed that the decidual immune cell profile is
      characteristic of an individual animal and is consistently maintained across
      successive pregnancies, suggesting that the uterine immune environment in
      pregnancy is carefully regulated in the rhesus monkey decidua.

PMID- 21900682
TI  - Minimal fertility defects in mice deficient in oocyte-expressed Smad4.
AB  - Bidirectional signaling between oocytes and granulosa cells is required for
      normal folliculogenesis. Oocyte-secreted members of the transforming growth
      factor beta (TGFB) family, growth differentiation factor 9 (GDF9), and bone
      morphogenetic protein 15 (BMP15) are well-known mediators of granulosa cell
      function. Deletion in granulosa cells of Smad4, the common SMAD mediating all
      canonical TGFB-related protein signals, results in infertility. Reciprocal
      signaling by granulosa cell-expressed TGFB family ligands, such as activin, to
      the oocyte during follicle development has been proposed but not tested in vivo
      using conditional knockout mice. Therefore, we generated two oocyte-specific
      conditional knockout models for the common SMAD, Smad4, using cre recombinase
      expression from either the zona pellucida 3 (Zp3) or Gdf9 promoter. Cre
      expression from the Gdf9 promoter occurs at a slightly earlier time point in
      follicle development than from Zp3. Deletion of Smad4 using Zp3cre had no effect
      on fertility, while deletion of Smad4 with Gdf9icre resulted in a slight, but
      significant, reduction in litter size. These mouse models suggest a novel,
      although minor, role for Smad4 in the oocyte restricted to the primordial
      follicle stage.

PMID- 21900684
TI  - Importin alpha2-interacting proteins with nuclear roles during mammalian
      spermatogenesis.
AB  - Spermatogenesis, the process of generating haploid sperm capable of fertilizing
      the female gamete, requires the timely transport into the nucleus of
      transcription and chromatin-remodeling factors, mediated by members of the
      importin (IMP) superfamily. Previous IMP expression profiling implies a role for
      IMPalpha2 in testicular germ cells late in spermatogenesis. To identify
      interacting proteins of IMPalpha2 that are potential drivers of germ cell
      development, we performed yeast two-hybrid screening of an adult mouse testis
      library. IMPalpha2 interactions were verified by coimmunoprecipitation
      approaches, whereas immunohistochemical staining of testis sections confirmed
      their coexpression with IMPalpha2 in specific testicular cell types. Key
      interactors identified were a novel isoform of a cysteine and histidine rich
      protein (Chrp), a protein inhibitor of activated STAT (PIAS) family member
      involved in transcriptional regulation and sumoylation, Androgen receptor
      interacting protein 3 (Arip3), and Homologous protein 2 (Hop2), known to be
      involved in homologous chromosome pairing and recombination, all of which are
      highly expressed in the testis and show mRNA expression profiles similar to that
      of IMPalpha2 throughout testicular development. This is the first study to
      identify binding partners of IMPalpha2 in the developmental context of germ line
      development, and we propose that the regulated expression and timely IMPalpha2
      mediated nuclear transport of these proteins may coordinate events during
      spermatogenesis, with IMPalpha2-mediated nuclear localization representing a
      potentially critical developmental switch in the testis.

PMID- 21900683
TI  - Immunoprotective properties of primary Sertoli cells in mice: potential
      functional pathways that confer immune privilege.
AB  - Primary Sertoli cells isolated from mouse testes survive when transplanted across
      immunological barriers and protect cotransplanted allogeneic and xenogeneic cells
      from rejection in rodent models. In contrast, the mouse Sertoli cell line (MSC-1)
      lacks immunoprotective properties associated with primary Sertoli cells. In this
      study, enriched primary Sertoli cells or MSC-1 cells were transplanted as
      allografts into the renal subcapsular area of naive BALB/c mice, and their
      survival in graft sites was compared. While Sertoli cells were detected within
      the grafts with 100% graft survival throughout the 20-day study, MSC-1 cells were
      rejected between 11 and 14 days, with 0% graft survival at 20 days
      posttransplantation. Nonetheless, the mechanism for primary Sertoli cell survival
      and immunoprotection remains unresolved. To identify immune factors or functional
      pathways potentially responsible for immune privilege, gene expression profiles
      of enriched primary Sertoli cells were compared with those of MSC-1 cells.
      Microarray analysis identified 2369 genes in enriched primary Sertoli cells that
      were differentially expressed at +/-4-fold or higher levels than in MSC-1 cells.
      Ontological analyses identified multiple immune pathways, which were used to
      generate a list of 340 immune-related genes. Three functions were identified in
      primary Sertoli cells as potentially important for establishing immune privilege:
      suppression of inflammation by specific cytokines and prostanoid molecules,
      slowing of leukocyte migration by controlled cell junctions and actin
      polymerization, and inhibition of complement activation and membrane-associated
      cell lysis. These results increase our understanding of testicular immune
      privilege and, in the long-term, could lead to improvements in transplantation
      success.

PMID- 21900685
TI  - Copper/zinc superoxide dismutase insufficiency impairs progesterone secretion and
      fertility in female mice.
AB  - Copper/zinc superoxide dismutase (CuZn-SOD, SOD1) is one of the major antioxidant
      enzymes, and is localized in the cytoplasm to scavenge superoxide. To investigate
      the physiological role of SOD1 in the ovaries, we analyzed the fertility of Sod1
      deficient female mice. To evaluate their hormonal metabolism, we measured
      pituitary and ovarian hormone levels in the plasma of the mutant mice. Plasma
      follicle-stimulating hormone, luteinizing hormone, and estradiol were not altered
      in the mutant compared to the wild-type females, while the plasma progesterone
      level was significantly reduced in the mutant females. Furthermore, the mutant
      mice showed decreased progesterone secretion under the condition of
      superovulation. In a histochemical analysis, we observed a remarkable reduction
      in the corpus luteum area in the mutant ovaries without atrophic changes. The
      mutant mice also displayed enhanced superoxide generation in the region
      surrounding the corpora lutea, which was associated with increased apoptotic
      cells and suppressed vasculature. These results suggested that SOD1 deficiency
      dysregulated luteal formation because of increased superoxide generation in the
      ovary. In vitro fertilization experiments showed no abnormal fertilization of
      Sod1-deficient oocytes. In addition, when Sod1-deficient embryos were transferred
      into the oviducts of wild-type females, mutant embryos developed at a normal
      rate, indicating that SOD1 deficiency in embryos did not cause miscarriage in the
      uterus of wild-type females. These results indicated that increased intracellular
      ROS impaired luteal formation and progesterone production in the mutant females,
      thus suggesting that SOD1 plays a crucial role in both the luteal function and
      the maintenance of fertility in female mice.

PMID- 21900686
TI  - Abnormal reproductive patterns in Przewalski's mares are associated with a loss
      in gene diversity.
AB  - The ex situ population of the Przewalski's horse (Equus ferus przewalskii) is not
      self-sustaining (20% foaling rate), and the demography is skewed toward aging
      individuals with low gene diversity. We designed the present study to gain a
      better understanding of the reproductive biology of the Przewalski's mare and to
      determine whether age and gene diversity influenced reproductive function. Urine
      samples were collected 3-7 days/wk from 19 mares from May to September, and
      ultrasound examinations of follicular structures were performed 3 days/wk for 5
      wk from May through July in nine individuals. A high proportion of mares
      exhibited abnormal (endocrine, 5 [26.3%] of 19; follicular, 2 [22.2%] of 9) or
      acyclic (endocrine, 4 [21.1%] of 19; follicular, 3 [33.3%] of 9) reproductive
      patterns. In four cyclic mares, estrous cycle length was 25.1 +/- 1.2 days, with
      12.2 +/- 0.9 days of diestrus. Follicles in cyclic mares grew 1.2 +/- 0.6 mm per
      day and ovulated after reaching 40.4 +/- 8.9 mm. Mares with a high coefficient of
      inbreeding excreted reduced levels of mean urinary estrogens (r(2) = 0.476, P <
      0.05), but age had no significant impact on reproductive patterns in this
      population. Overall, these data suggest that long-term genetic management of this
      population is necessary to maintain reproductive fitness.

PMID- 21900687
TI  - Myostatin promotes the wasting of human myoblast cultures through promoting
      ubiquitin-proteasome pathway-mediated loss of sarcomeric proteins.
AB  - Myostatin is a negative regulator of skeletal muscle growth and in fact acts as a
      potent inducer of "cachectic-like" muscle wasting in mice. The mechanism of
      action of myostatin in promoting muscle wasting has been predominantly studied in
      murine models. Despite numerous reports linking elevated levels of myostatin to
      human skeletal muscle wasting conditions, little is currently known about the
      signaling mechanism(s) through which myostatin promotes human skeletal muscle
      wasting. Therefore, in this present study we describe in further detail the
      mechanisms behind myostatin regulation of human skeletal muscle wasting using an
      in vitro human primary myotube atrophy model. Treatment of human myotube
      populations with myostatin promoted dramatic myotubular atrophy. Mechanistically,
      myostatin-induced myotube atrophy resulted in reduced p-AKT concomitant with the
      accumulation of active dephosphorylated Forkhead Box-O (FOXO1) and FOXO3. We
      further show that addition of myostatin results in enhanced activation of atrogin
      1 and muscle-specific RING finger protein 1 (MURF1) and reduced expression of
      both myosin light chain (MYL) and myosin heavy chain (MYH). In addition, we found
      that myostatin-induced loss of MYL and MYH proteins is dependent on the activity
      of the proteasome and mediated via SMAD3-dependent regulation of FOXO1 and
      atrogin-1. Therefore, these data suggest that the mechanism through which
      myostatin promotes muscle wasting is very well conserved between species, and
      that myostatin-induced human myotube atrophy is mediated through inhibition of
      insulin-like growth factor (IGF)/phosphoinositide 3-kinase (PI3-K)/AKT signaling
      and enhanced activation of the ubiquitin-proteasome pathway and elevated protein
      degradation.

PMID- 21900689
TI  - Induction of brain natriuretic peptide and monocyte chemotactic protein-1 gene
      expression by oxidized low-density lipoprotein: relevance to ischemic heart
      failure.
AB  - Brain natriuretic peptide (BNP) and monocyte chemotactic protein-1 (MCP-1) are
      biomarkers of heart failure (HF). The aim of the present study was to determine
      the role of oxidized low-density lipoprotein (Ox-LDL) in the induction of these
      biomarkers and the signaling pathways involved in vitro. Incubation of HL-1
      cardiomyocytes and human myocytes with Ox-LDL induced the expression of BNP and
      MCP-1 genes, while native LDL had no effect. When peroxides associated with Ox
      LDL were reduced to hydroxides, the ability to induce BNP and MCP-1 gene
      expression was abolished. Furthermore, exposure of HL-1 cells to ischemic
      conditions alone had no effect on BNP gene expression, while ischemia followed by
      reperfusion resulted in increased expression of BNP gene. Inhibitors of ERK and
      JNK inhibited the induction of BNP. Signaling array results suggested that the
      induction of both MAPK and NF-kappaB pathways is involved in the induction of BNP
      by Ox-LDL. These results suggest that Ox-LDL or peroxidized lipids formed in
      oxidatively stressed myocytes during ischemia-reperfusion injury may play a role
      in the induction of BNP and MCP-1.

PMID- 21900688
TI  - Role of caveolin-1 in endothelial BKCa channel regulation of vasoreactivity.
AB  - A novel vasodilatory influence of endothelial cell (EC) large-conductance Ca(2+)
      activated K(+) (BK(Ca)) channels is present following in vivo exposure to chronic
      hypoxia (CH) and may exist in other pathological states. However, the mechanism
      of channel activation that results in altered vasoreactivity is unknown. We
      tested the hypothesis that CH removes an inhibitory effect of the scaffolding
      domain of caveolin-1 (Cav-1) on EC BK(Ca) channels to permit activation, thereby
      affecting vasoreactivity. Experiments were performed on gracilis resistance
      arteries and ECs from control and CH-exposed (380 mmHg barometric pressure for 48
      h) rats. EC membrane potential was hyperpolarized in arteries from CH-exposed
      rats and arteries treated with the cholesterol-depleting agent methyl-beta
      cyclodextrin (MBCD) compared with controls. Hyperpolarization was reversed by the
      BK(Ca) channel antagonist iberiotoxin (IBTX) or by a scaffolding domain peptide
      of Cav-1 (AP-CAV). Patch-clamp experiments documented an IBTX-sensitive current
      in ECs from CH-exposed rats and in MBCD-treated cells that was not present in
      controls. This current was enhanced by the BK(Ca) channel activator NS-1619 and
      blocked by AP-CAV or cholesterol supplementation. EC BK(Ca) channels displayed
      similar unitary conductance but greater Ca(2+) sensitivity than BK(Ca) channels
      from vascular smooth muscle. Immunofluorescence imaging demonstrated greater
      association of BK(Ca) alpha-subunits with Cav-1 in control arteries than in
      arteries from CH-exposed rats, although fluorescence intensity for each protein
      did not differ between groups. Finally, AP-CAV restored myogenic and
      phenylephrine-induced constriction in arteries from CH-exposed rats without
      affecting controls. AP-CAV similarly restored diminished reactivity to
      phenylephrine in control arteries pretreated with MBCD. We conclude that CH
      unmasks EC BK(Ca) channel activity by removing an inhibitory action of the Cav-1
      scaffolding domain that may depend on cellular cholesterol levels.

PMID- 21900691
TI  - Stretch-activated calcium channel protein TRPC1 is correlated with the different
      degrees of the dystrophic phenotype in mdx mice.
AB  - In Duchenne muscular dystrophy (DMD) and in the mdx mouse model of DMD, the lack
      of dystrophin is related to enhanced calcium influx and muscle degeneration.
      Stretch-activated channels (SACs) might be directly involved in the pathology of
      DMD, and transient receptor potential cation channels have been proposed as
      likely candidates of SACs. We investigated the levels of transient receptor
      potential canonical channel 1 (TRPC1) and the effects of streptomycin, a SAC
      blocker, in muscles showing different degrees of the dystrophic phenotype. Mdx
      mice (18 days old, n = 16) received daily intraperitoneal injections of
      streptomycin (182 mg/kg body wt) for 18 days, followed by removal of the
      diaphragm, sternomastoid (STN), biceps brachii, and tibialis anterior muscles.
      Control mdx mice (n = 37) were injected with saline. Western blot analysis showed
      higher levels of TRPC1 in diaphragm muscle compared with STN and limb muscles.
      Streptomycin reduced creatine kinase and prevented exercise-induced increases of
      total calcium and Evans blue dye uptake in diaphragm and in STN muscles. It is
      suggested that different levels of the stretch-activated calcium channel protein
      TRPC1 may contribute to the different degrees of the dystrophic phenotype seen in
      mdx mice. Early treatment designed to regulate the activity of these channels may
      ameliorate the progression of dystrophy in the most affected muscle, the
      diaphragm.

PMID- 21900690
TI  - Vascular smooth muscle insulin resistance, but not hypertrophic signaling, is
      independent of angiotensin II-induced IRS-1 phosphorylation by JNK.
AB  - Angiotensin II (ANG II) has been implicated in the pathogenesis of diabetic micro
      and macrovascular disease. In vascular smooth muscle cells (VSMCs), ANG II
      phosphorylates and degrades insulin receptor substrate-1 (IRS-1). While the
      pathway responsible for IRS-1 degradation in this system is unknown, c-Jun NH(2)
      terminal kinase (JNK) has been linked with serine phosphorylation of IRS-1 and
      insulin resistance. We investigated the role of JNK in ANG II-induced IRS-1
      phosphorylation, degradation, Akt activation, glucose uptake, and hypertrophic
      signaling, focusing on three IRS-1 phosphorylation sites: Ser302, Ser307, and
      Ser632. Maximal IRS-1 phosphorylation on Ser632 occurred at 5 min, on Ser307 at
      30 min, and on Ser302 at 60 min. The JNK inhibitor SP600125 reduced ANG II
      induced IRS-1 Ser307 phosphorylation (by 80%), IRS-1 Ser302 phosphorylation (by
      70%), and IRS-1 Ser632 phosphorylation (by 50%). However, JNK inhibition had no
      effect on ANG II-mediated IRS-1 degradation, nor did it reverse the ANG II
      induced decrease in Akt phosphorylation or glucose uptake. Transfection of VSMCs
      with mutants S307A, S302A, or S632A of IRS-1 did not block ANG II-mediated IRS-1
      degradation. In contrast, JNK inhibition attenuated insulin-induced upregulation
      of collagen and smooth muscle alpha-actin in ANG II-pretreated cells. We conclude
      that phosphorylation of Ser307, Ser302, and Ser632 of IRS-1 is not involved in
      ANG II-mediated IRS-1 degradation, and that JNK alone does not mediate ANG II
      stimulated IRS-1 degradation, but rather is responsible for the hypertrophic
      effects of insulin on smooth muscle.

PMID- 21900692
TI  - Historical perspectives in fat cell biology: the fat cell as a model for the
      investigation of hormonal and metabolic pathways.
AB  - For many years, there was little interest in the biochemistry or physiology of
      adipose tissue. It is now well recognized that adipocytes play an important
      dynamic role in metabolic regulation. They are able to sense metabolic states via
      their ability to perceive a large number of nervous and hormonal signals. They
      are also able to produce hormones, called adipokines, that affect nutrient
      intake, metabolism and energy expenditure. The report by Rodbell in 1964 that
      intact fat cells can be obtained by collagenase digestion of adipose tissue
      revolutionized studies on the hormonal regulation and metabolism of the fat cell.
      In the context of the advent of systems biology in the field of cell biology, the
      present seems an appropriate time to look back at the global contribution of the
      fat cell to cell biology knowledge. This review focuses on the very early
      approaches that used the fat cell as a tool to discover and understand various
      cellular mechanisms. Attention essentially focuses on the early investigations
      revealing the major contribution of mature fat cells and also fat cells
      originating from adipose cell lines to the discovery of major events related to
      hormone action (hormone receptors and transduction pathways involved in hormonal
      signaling) and mechanisms involved in metabolite processing (hexose uptake and
      uptake, storage, and efflux of fatty acids). Dormant preadipocytes exist in the
      stroma-vascular fraction of the adipose tissue of rodents and humans; cell
      culture systems have proven to be valuable models for the study of the processes
      involved in the formation of new fat cells. Finally, more recent insights into
      adipocyte secretion, a completely new role with major metabolic impact, are also
      briefly summarized.

PMID- 21900693
TI  - A novel, selective inhibitor of fibroblast growth factor receptors that shows a
      potent broad spectrum of antitumor activity in several tumor xenograft models.
AB  - The fibroblast growth factor receptors (FGFR) are tyrosine kinases that are
      present in many types of endothelial and tumor cells and play an important role
      in tumor cell growth, survival, and migration as well as in maintaining tumor
      angiogenesis. Overexpression of FGFRs or aberrant regulation of their activities
      has been implicated in many forms of human malignancies. Therefore, targeting
      FGFRs represents an attractive strategy for development of cancer treatment
      options by simultaneously inhibiting tumor cell growth, survival, and migration
      as well as tumor angiogenesis. Here, we describe a potent, selective, small
      molecule FGFR inhibitor, (R)-(E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)ethoxy)
      1H-indazol-3yl)vinyl)-1H-pyrazol-1-yl)ethanol, designated as LY2874455. This
      molecule is active against all 4 FGFRs, with a similar potency in biochemical
      assays. It exhibits a potent activity against FGF/FGFR-mediated signaling in
      several cancer cell lines and shows an excellent broad spectrum of antitumor
      activity in several tumor xenograft models representing the major FGF/FGFR
      relevant tumor histologies including lung, gastric, and bladder cancers and
      multiple myeloma, and with a well-defined pharmacokinetic/pharmacodynamic
      relationship. LY2874455 also exhibits a 6- to 9-fold in vitro and in vivo
      selectivity on inhibition of FGF- over VEGF-mediated target signaling in mice.
      Furthermore, LY2874455 did not show VEGF receptor 2-mediated toxicities such as
      hypertension at efficacious doses. Currently, this molecule is being evaluated
      for its potential use in the clinic.

PMID- 21900694
TI  - Benefits and mechanisms of recovery among peer providers with psychiatric
      illnesses.
AB  - Providing peer support to individuals with psychiatric disabilities has emerged
      as a promising modality of mental health services. These services are delivered
      by individuals who experience mental illnesses themselves. The purpose of this
      study was to explore how working as a peer provider can enhance personal
      recovery. The study was conducted with 31 peer providers employed in a variety of
      mental health agencies. Data were collected through face-to-face semistructured
      interviews and analyzed using a grounded theory approach. Qualitative analysis
      revealed a wide range of recovery benefits for the peer providers. The benefits
      span across five wellness domains: foundational, emotional, spiritual, social,
      and occupational. In addition, analysis revealed five role-related and five work
      environment-related mechanisms of beneficial impact. The role of sharing one's
      personal story is highlighted as contributing to positively reauthoring one's
      self-narrative. Implications for peer training, job development, and workplace
      supports are discussed.

PMID- 21900695
TI  - Understanding ethnic and other socio-demographic differences in patient
      experience of primary care: evidence from the English General Practice Patient
      Survey.
AB  - BACKGROUND: Ethnic minorities and some other patient groups consistently report
      lower scores on patient surveys, but the reasons for this are unclear. This study
      examined whether low scores of ethnic minority and other socio-demographic groups
      reflect their concentration in poorly performing primary care practices, and
      whether any remaining differences are consistent across practices. METHODS: Using
      data from the 2009 English General Practice Patient Survey (2 163 456 respondents
      from 8267 general practices) this study examined associations between patient
      socio-demographic characteristics and 11 measures of patient-reported experience.
      FINDINGS: South Asian and Chinese patients, younger patients, and those in poor
      health reported a less positive primary care experience than White patients,
      older patients and those in better health. For doctor communication, about half
      of the overall difference associated with South Asian patients (ranging from -6
      to -9 percentage points) could be explained by their concentration in practices
      with low scores, but the other half arose because they reported less positive
      experiences than White patients in the same practices. Practices varied
      considerably in the direction and extent of ethnic differences. In some practices
      ethnic minority patients reported better experience than White patients.
      Differences associated with gender, Black ethnicity and deprivation were small
      and inconsistent. CONCLUSION: Substantial ethnic differences in patient
      experience exist in a national healthcare system providing universal coverage.
      Improving the experience of patients in low-scoring practices would not only
      improve the quality of care provided to their White patients but it would also
      substantially reduce ethnic group differences in patient experience. There were
      large variations in the experiences reported by ethnic minority patients in
      different practices: practices with high patient experience scores from ethnic
      minority patients could be studied as models for quality improvement.

PMID- 21900697
TI  - The van Niel International Prize for Studies in Bacterial Systematics, awarded by
      The University of Queensland Awarded in 2011 to George M. Garrity.
AB  - The Senate of The University of Queensland, on the recommendation of a panel of
      experts of the International Committee on Systematics of Prokaryotes, is pleased
      to present the van Niel International Prize for Studies in Bacterial Systematics
      for the triennium 2009-2011 to Professor George M. Garrity in recognition of his
      contribution made to the field of bacterial systematics. The award, established
      in 1986 by Professor V. B. D. Skerman of The University of Queensland, honours
      the contribution of scholarship in the field of microbiology by Professor
      Cornelis Bernardus van Niel.

PMID- 21900698
TI  - Importance of past occupational exposures in the rising incidence of idiopathic
      pulmonary fibrosis in the U.K.

PMID- 21900699
TI  - Selfish genes and reproductive fitness.

PMID- 21900700
TI  - Policies for patient access to clinical data via PHRs: current state and
      recommendations.
AB  - OBJECTIVE: Healthcare delivery organizations are increasingly using online
      personal health records (PHRs) to provide patients with direct access to their
      clinical information; however, there may be a lack of consistency in the data
      made available. We aimed to understand the general use and functionality of PHRs
      and the organizational policies and decision-making structures for making data
      available to patients. MATERIALS AND METHODS: A cross-sectional survey was
      administered by telephone structured interview to 21 organizations to determine
      the types of data made available to patients through PHRs and the presence of
      explicit governance for PHR data release. Organizations were identified based on
      a review of the literature, PHR experts, and snowball sampling. Organizations
      that did not provide patients with electronic access to their data via a PHR were
      excluded. RESULTS: Interviews were conducted with 17 organizations for a response
      rate of 81%. Half of the organizations had explicit governance in the form of a
      written policy that outlined the data types made available to patients. Overall,
      88% of the organizations used a committee structure for the decision-making
      process and included senior management and information services. All
      organizations sought input from clinicians. Discussion There was considerable
      variability in the types of clinical data and the time frame for releasing these
      data to patients. Variability in data release policies may have implications for
      PHR use and adoption. CONCLUSIONS: Future policy activities, such as requirement
      specification for the latter stages of Meaningful Use, should be leveraged as an
      opportunity to encourage standardization of functionality and broad deployment of
      PHRs.

PMID- 21900701
TI  - Exploiting domain information for Word Sense Disambiguation of medical documents.
AB  - OBJECTIVE: Current techniques for knowledge-based Word Sense Disambiguation (WSD)
      of ambiguous biomedical terms rely on relations in the Unified Medical Language
      System Metathesaurus but do not take into account the domain of the target
      documents. The authors' goal is to improve these methods by using information
      about the topic of the document in which the ambiguous term appears. DESIGN: The
      authors proposed and implemented several methods to extract lists of key terms
      associated with Medical Subject Heading terms. These key terms are used to
      represent the document topic in a knowledge-based WSD system. They are applied
      both alone and in combination with local context. MEASUREMENTS: A standard
      measure of accuracy was calculated over the set of target words in the widely
      used National Library of Medicine WSD dataset. RESULTS AND DISCUSSION: The
      authors report a significant improvement when combining those key terms with
      local context, showing that domain information improves the results of a WSD
      system based on the Unified Medical Language System Metathesaurus alone. The best
      results were obtained using key terms obtained by relevance feedback and weighted
      by inverse document frequency.

PMID- 21900703
TI  - Intracompartmental pressure testing: results of an international survey of
      current clinical practice, highlighting the need for standardised protocols.
AB  - Despite more recent non-invasive modalities generating some credence in the
      literature, intracompartmental pressure testing is still considered the 'gold
      standard' for investigating chronic exertional compartment syndrome (CECS).
      Intracompartmental pressure testing, when used correctly, has been shown to be
      accurate and reliable. However, it is a user-dependent investigation, and the
      manner in which the investigation is conducted plays a large role in the outcome
      of the test. Despite this, a standard, reproducible protocol for
      intracompartmental pressure testing has not been described. This results in
      confusion regarding interpretation of results and reduces the tests' reliability.
      A summary of the current understanding of CECS is presented, along with the
      results of a survey of specialists in Australia and New Zealand who perform
      intracompartmental pressure testing, which confirms that a uniform approach is
      currently not used in clinical practice. This highlights the need for a consensus
      and standardised approach to intracompartmental pressure testing.

PMID- 21900702
TI  - Clinician characteristics and use of novel electronic health record functionality
      in primary care.
AB  - BACKGROUND: Conventional wisdom holds that older, busier clinicians who see
      complex patients are less likely to adopt and use novel electronic health record
      (EHR) functionality. METHODS: To compare the characteristics of clinicians who
      did and did not use novel EHR functionality, we conducted a retrospective
      analysis of the intervention arm of a randomized trial of new EHR-based tobacco
      treatment functionality. RESULTS: The novel functionality was used by 103 of 207
      (50%) clinicians. Staff physicians were more likely than trainees to use the
      functionality (64% vs 37%; p<0.001). Clinicians who graduated more than 10 years
      previously were more likely to use the functionality than those who graduated
      less than 10 years previously (64% vs 42%; p<0.01). Clinicians with higher
      patient volumes were more likely to use the functionality (lowest quartile of
      number of patient visits, 25%; 2nd quartile, 38%; 3rd quartile, 65%; highest
      quartile, 71%; p<0.001). Clinicians who saw patients with more documented
      problems were more likely to use the functionality (lowest tertile of documented
      patient problems, 38%; 2nd tertile, 58%; highest tertile, 54%; p=0.04). In
      multivariable modeling, independent predictors of use were the number of patient
      visits (OR 1.2 per 100 additional patients; 95% CI 1.1 to 1.4) and number of
      documented problems (OR 2.9 per average additional problem; 95% CI 1.4 to 6.1).
      CONCLUSIONS: Contrary to conventional wisdom, clinically busier physicians seeing
      patients with more documented problems were more likely to use novel EHR
      functionality.

PMID- 21900704
TI  - A-Z of nutritional supplements: dietary supplements, sports nutrition foods and
      ergogenic aids for health and performance: part 24.

PMID- 21900705
TI  - Coding of heart failure diagnoses in Saskatchewan: a validation study of hospital
      discharge abstracts.
AB  - BACKGROUND: Validity of Heart Failure (HF) diagnoses from administrative records
      has not been extensively evaluated, especially with respect to small / unselected
      hospitals. OBJECTIVES: To determine the positive predictive value of a primary /
      most responsible diagnosis of HF among a general population of subjects
      discharged from Saskatchewan hospitals. METHODS: Using administrative health
      records from the Province of Saskatchewan, Canada, we identified subjects
      experiencing their first HF hospitalization between 1994 and 2003. From this
      cohort, we randomly selected 500 subjects for individual validation using
      Framingham and Carlson criteria. RESULTS: The 466 charts available for analysis,
      74% (345/466) and 63.9% (298/466) of subjects met criteria for a clinical
      diagnosis of HF based on Framingham or Carlson criteria, respectively; 57.5%
      (268/466) met both criterion. Provincial hospitals (located in the largest urban
      centres) were associated with the highest proportion of confirmed HF diagnoses
      (87.8% by Framingham criteria) compared to progressively smaller hospitals
      (regional 77.9%; district 64.2%; and community 60.0%). Accuracy also differed
      when stratified by physician category. Cardiologists and internists were
      associated with the highest rates of confirmed diagnoses [(97.5% (39 / 40) and
      85.0% (34 / 40)]) compared to general practitioners [(73.1% (95 / 130)]) and
      other physicians [(69.1% (177 / 256)]), by Framingham criteria. CONCLUSIONS:
      Hospital discharge abstracts indicating HF are frequently inaccurate. These
      findings have important implications for the epidemiologic study of HF as well as
      the clinical management of patients.

PMID- 21900706
TI  - A need for closer examination of FASD by the criminal justice system: has the
      call been answered?
AB  - Individuals with FASD exhibit deficits in many domains that can include memory,
      learning, behavioural inhibition, executive functioning, interpersonal skills,
      and language. These deficits have serious implications for affected persons when
      they become engaged in the legal system. In 2004, Moore and Green reviewed case
      law and psychological literature which suggested that FASD-related deficits
      placed affected individuals at a significant disadvantage in the justice system.
      According to them, this disadvantage stemmed from the limited awareness and
      knowledge of FASD demonstrated by key players in the justice system, as well as
      the scarcity of effective interventions in place to rehabilitate affected
      defendants. The aim of the current paper is to assess the extent to which
      awareness of FASD-related issues in the Canadian justice system has advanced
      since the publication of Moore and Green's conclusions. First, the deficits
      associated with FASD and their implications for the justice system are described.
      Next, recent case law and psychological evidence are reviewed as we consider
      issues of witness reliability and false confessions. The significance of FASD for
      sentencing, fitness to stand trial, and the Not Criminally Responsible by Reason
      of Mental Disorder defence are also briefly discussed. Finally, emerging system
      wide responses to FASD-related issues are presented. Overall, it appears that the
      call for closer examination of FASD by the justice system has been answered, but
      a need for increased education and awareness remains.

PMID- 21900707
TI  - A differential approach for examining the behavioural phenotype of fetal alcohol
      spectrum disorders.
AB  - BACKGROUND: In 2006, Nash and colleagues published results suggesting that
      individual items from the Child Behavior Checklist (CBCL) could be used as a
      screening tool that was highly sensitive in differentiating children with FASD
      from controls and children with Attention Deficit Hyperactivity Disorder (ADHD).
      Since many of the items referred to features of Oppositional Defiant/Conduct
      Disorder (ODD/CD), it was not clear whether the items reflected comorbidity with
      ODD/CD, or were unique to children with FASD. OBJECTIVES: The present study
      sought to replicate the results of our 2006 paper using a new and larger sample,
      which also includes a group of children diagnosed with ODD/CD. METHODS:
      Retrospective psychological chart review was conducted on 56 children with FASD,
      50 with ADHD, 60 with ODD/CD, and 50 normal control (NC) children. Receiver
      operating characteristic curve (ROC) analysis of CBCL items discriminating FASD
      from NC was used to compare FASD to the ADHD and ODD/CD groups. RESULTS: ROC
      analyses showed scores of a) 3 or higher on 10 items differentiated FASD from NC
      with a sensitivity of 98%, specificity of 42% and b) 2 or higher on 5 items
      reflecting oppositional behaviors differentiated FASD from ADHD with a
      sensitivity of 89% and specificity of 42%. CONCLUSION: Our findings partially
      replicate the results of our 2006 study and additionally elucidate the
      behavioural differences between children with FASD and those with ODD/CD. The
      proposed screening tool is currently the only tool available that is empirically
      derived and able to differentiate children with FASD from children with
      clinically similar profiles.

PMID- 21900708
TI  - A generic organ based ontology system, applied to vertebrate heart anatomy,
      development and physiology.
AB  - We present a novel approach to modelling biological information using ontologies.
      The system interlinks three ontologies, comprising anatomical, developmental and
      taxonomical information, and includes instances of structures for different
      species. The framework is constructed for comparative analyses in the field of
      evolutionary development. We have applied the approach to the vertebrate heart
      and present four case studies of the functionality of the system, focusing on
      cross-species comparisons, developmental studies, physiological studies and 3D
      visualisation.

PMID- 21900709
TI  - Protein analysis tools and services at IBIVU.
AB  - During the last years several new tools applicable to protein analysis have made
      available on the IBIVU web site. Recently, a number of tools, ranging from
      multiple sequence alignment construction to domain prediction, have been updated
      and/or extended with services for programmatic access using SOAP. We provide an
      overview of these tools and their application.

PMID- 21900710
TI  - Does antiviral therapy prevent hepatocellular carcinoma?
AB  - Chronic infection with HBV or HCV can lead to the development of hepatocellular
      carcinoma (HCC). The major risk factors for HBV-related HCC are persistent
      presence of hepatitis B e antigen (HBeAg) and/or high serum HBV DNA levels, and
      cirrhosis. The major risk factor for HCV-related HCC is cirrhosis. One randomized
      double blind controlled trial of lamivudine in patients with HBeAg and/or high
      serum HBV DNA levels showed that antiviral therapy prevented disease progression
      and reduced the incidence of HCC. A beneficial effect of antiviral therapy on the
      risk of HCC has also been shown in cohort studies and meta-analyses, particularly
      among responders. Several randomized controlled trials of interferon in patients
      with HCV-related cirrhosis showed that treated patients had a lower incidence of
      HCC. A greater effect was observed in patients who achieved sustained virological
      response, while the benefit in non-responders is unclear. Antiviral therapies for
      hepatitis B and hepatitis C can prevent but not completely eliminate HCC.
      Improvement in identification of infected persons, accessibility of care and
      affordability of treatment is needed for antiviral therapy to have a major impact
      on the global incidence of HCC.

PMID- 21900711
TI  - Effect of raltegravir on the total and unintegrated proviral HIV DNA during
      raltegravir-based HAART.
AB  - BACKGROUND: Raltegravir is the first approved antiretroviral able to prevent HIV
      genome integration into the host chromosomes. The aim of the study is to test if
      raltegravir plasma concentrations can be associated with proviral DNA decline
      during raltegravir-based salvage therapy. METHODS: A total of 33 multidrug
      resistant HIV-infected patients were enrolled in a longitudinal open-label pilot
      study and completed a 24-week follow-up. The CD4(+) T-cell count, plasma viral
      load, proviral HIV DNA and two-long-terminal repeat (2-LTR) circular forms were
      assessed at baseline, day 14, 30, 60, 90 and 180. The raltegravir trough
      concentration (C (trough)) was measured by HPLC-ultraviolet and patients were
      divided into two groups according to the median raltegravir C (trough). RESULTS:
      The mean+/-SD values of baseline HIV RNA, CD4(+) T-cell count and HIV DNA were
      4.4+/-0.82 log copies/ml, 256+/-177 cells/mm(3) , and 2,668+/-4,721 copies/10(6)
      peripheral blood mononuclear cells, respectively. Despite a transient increase of
      total DNA at week 2, a marked proviral DNA decay (P=0.01) with an increase of the
      2-LTR unintegrated/total DNA ratio (P=0.06) over time was observed. At univariate
      analysis, no correlation between raltegravir C(trough) and classical virological
      parameters was observed. Nevertheless, the decay of proviral HIV DNA was more
      pronounced in patients displaying C(trough)<158 ng/ml with respect to those with
      C(trough)>158 ng/ml (P=0.046). CONCLUSIONS: Successful raltegravir-based therapy
      produces a significant decline in proviral DNA and is associated with an increase
      of the unintegrated/total DNA ratio. Further studies are necessary to define the
      possible role of pharmacokinetic raltegravir monitoring and the biological
      meaning of unintegrated proviral DNA.

PMID- 21900713
TI  - Considerable under-treatment of chronic HCV infection in HIV patients despite
      acceptable sustained virological response rates in a real-life setting.
AB  - BACKGROUND: According to guidelines, treatment of HCV infection should be
      considered a priority in HIV-HCV-coinfected patients. METHODS: This multicentre
      study includes HIV-HCV-coinfected patients diagnosed since 2001 in 14
      participating centres in Austria and Germany. Demographic and virological data
      were recorded. Factors associated with non-initiation of HCV treatment were
      identified. RESULTS: Among 9,524 HIV patients screened, 1,033 HIV-HCV-coinfected
      patients were identified (male/female: 760/273; age: 43+/-9 years; weight: 71+/
      12 kg; CD4(+) T-cell nadir: 255+/-189 cells/MUl; HCV RNA: 3.79*10(6) IU/ml; HIV
      RNA: 65*10(3) copies/ml). HCV genotype (GT) was predominantly GT-1 (62%). A total
      of 416 (40%) patients received HCV treatment, whereas 617 (60%) patients remained
      untreated. The main reasons for deferral of HCV treatment were patient refusal
      (20%), adherence/compliance (18%), active intravenous drug abuse (14%) and
      advanced immunodeficiency/AIDS (9%). Patients starting HCV treatment had
      significantly lower fibrosis stage (F2 versus F4; P<0.0001), higher CD4(+) T-cell
      count (530 cells/MUl versus 430 cells/MUl; P<0.0001), lower HIV RNA levels
      (18*10(3) copies/ml versus 47*10(3) copies/ml; P=0.0008) and higher alanine
      aminotransferase (ALT; 113 IU/ml versus 75 IU/ml; P<0.0001) than patients without
      initiation of HCV treatment. Age, HCV GTs, HCV RNA, haemoglobin levels, platelet
      count and white blood cell count were similar in patients receiving and in
      patients not receiving antiviral therapy. Multivariate analysis identified ALT
      levels (P<0.0001) and CD4(+) T-cell count (P<0.0001) as independent predictors of
      treatment uptake. The overall sustained virological response (SVR) was 41%
      (155/416), with GT-1 and non-GT1 patients achieving SVR rates of 29% and 48%,
      respectively. CONCLUSIONS: This large cohort study provides evidence for
      considerable under-treatment of chronic HCV infection in HIV patients. Despite
      acceptable treatment success in this real-life setting, HCV remains untreated in
      the majority of patients and often owing to potentially modifiable reasons.

PMID- 21900714
TI  - Liver interleukin-8 messenger RNA expression and interferon sensitivity
      determining region mutations relate to treatment response in hepatitis C 1b.
AB  - BACKGROUND: In vitro study has shown that mechanisms for inhibiting interferon
      (IFN)-alpha antiviral action by non-structural 5A protein include interaction
      with IFN-induced RNA-dependent protein kinase and induction of interleukin (IL)-8
      expression. Mutations in the non-structural 5A IFN sensitivity-determining region
      (ISDR) were reported to correlate with sustained virological response (SVR). IL-8
      is associated with the inhibition of IFN-alpha action. We investigated whether
      pretreatment ISDR mutations and hepatic IL-8 messenger RNA (mRNA) expression had
      an effect on the SVR rate under combination therapy. METHODS: A total of 53 HCV
      1b patients who completed 24 weeks of pegylated-IFN-alpha2b plus ribavirin, a 24
      week follow-up and had enough tissue specimens were enrolled. Liver biopsy was
      performed within 6 months before antiviral therapy. Hepatic IL-8 mRNA expression
      was measured by real-time reverse transcriptase PCR. RESULTS: Of 53 patients, 30
      exhibited SVR. Multivariate analysis revealed that hepatic IL-8 mRNA expression
      <1.5*10(-4) (OR 6.66, 95% CI 1.77-25.05) and ISDR mutations >=4 (OR 12.20, 95% CI
      1.23-125.00) were independent predictors of SVR. Fibrosis scores and alanine
      aminotransferase levels were predictive of hepatic IL-8 mRNA expression by
      multiple linear regression analysis (r(2)=0.204). CONCLUSIONS: SVR to combination
      therapy in hepatitis C 1b patients was associated with down-regulated hepatic IL
      8 mRNA expression and ISDR mutations. Fibrosis scores and alanine
      aminotransferase levels were predictive of hepatic IL-8 mRNA expression.

PMID- 21900712
TI  - Outcomes in the first year after initiation of first-line HAART among
      heterosexual men and women in the UK CHIC Study.
AB  - BACKGROUND: We analysed the influence of gender on use and outcomes of first-line
      HAART in a UK cohort. METHODS: Analyses included heterosexuals starting HAART
      from 1998-2007 with pre-treatment CD4(+) T-cell count<350 cells/mm(3) and viral
      load (VL)>500 copies/ml. Virological suppression (<50 copies/ml), virological
      rebound (>500 copies/ml), CD4(+) T-cell counts at 6 and 12 months, clinical
      events and treatment discontinuation/switch in the first year of HAART were
      compared using linear, logistic and Cox regression. RESULTS: Compared with women
      (n=2,179), men (n=1,487) were older and had lower CD4(+) T-cell count and higher
      VL at start of HAART. Median follow-up was 3.8 years (IQR 2.0-6.2). At 6 and 12
      months, 72.7% and 75.3% had VL<=50 copies/ml, with no large differences between
      genders at either time after adjustment for confounders (6 months, OR 0.92 [95%
      CI 0.76-1.13]; 12 months, OR 1.06 [95% CI 0.85-1.31]). Overall, 79.4% patients
      achieved virological suppression and 19.2% experienced virological rebound,
      without gender differences, although men had an increased risk of rebound after
      excluding pregnant women (adjusted relative hazard [RH] 1.33 [95% CI 1.04-1.71]).
      Mean CD4(+) T-cell count increases at 6 and 12 months were, respectively, 112 and
      156 cells/mm(3) overall, with mean differences between men and women of -14.6
      cells/mm(3) (95% CI -24.6--4.5) and -12.1 cells/mm(3) (95% CI -24.4-0.2) at 6 and
      12 months, respectively. Clinical progression was similar in men and women, but
      men were less likely to experience treatment discontinuation/switch (adjusted RH
      0.72 [95% CI 0.63-0.83]). CONCLUSIONS: Despite higher discontinuation rates among
      women, men had an increased risk of virological rebound and slightly poorer
      CD4(+) T-cell count responses. Identifying the reasons underlying treatment
      discontinuation/switch may help optimize treatment strategies for both genders.

PMID- 21900715
TI  - Effect of an induction period of pegylated interferon-alpha2a and ribavirin on
      early virological response in HIV-HCV-coinfected patients: results from the CORAL
      2 study.
AB  - BACKGROUND: It is uncertain whether a 4-week induction period of pegylated
      interferon and ribavirin increases early virological response (EVR) in HIV-HCV
      coinfected patients. METHODS: HIV and HCV genotype 1- and 4-coinfected subjects
      were randomized to receive pegylated interferon-alpha2a 270 MUg/week plus
      ribavirin 1,600 mg daily and epoetin-beta for 4 weeks, followed by pegylated
      interferon-alpha2a at standard dosages plus weight-based ribavirin (WBR) dosage
      for 8 weeks (induction arm [IA]), or pegylated interferon-alpha2a plus WBR for 12
      weeks (standard therapy arm [SA]). HCV RNA was determined at weeks 0, 1, 2, 3, 4,
      8 and 12. Ribavirin plasma trough concentrations were determined at weeks 4 (RBV
      C(4)) and 12 (RBV-C(12)). RESULTS: A total of 67 patients were included; 33 in
      the SA and 34 in the IA. Overall, 25% received nucleoside reverse transcriptase
      inhibitor (NRTI)-sparing regimens. More patients achieved an HCV RNA decrease >=1
      log(10) at week 4 in the IA than in the SA (62% versus 38%; P=0.017), but EVR
      rates were similar in the two groups (74% versus 59% in the IA and SA,
      respectively; P=0.15). Independent predictors of faster HCV RNA decrease at 12
      weeks were higher RBV-C(4) and younger age. RBV-C(4) were higher in patients
      allocated in the IA and in those receiving NRTIs (P=0.039). CONCLUSIONS: A 4-week
      induction with pegylated interferon-alpha2a plus ribavirin was associated with a
      greater decrease in HCV RNA at week 4; however, this did not translate into
      higher EVR rates. Higher RBV doses and avoidance of NRTI-sparing antiretroviral
      regimens might improve HCV treatment efficacy.

PMID- 21900716
TI  - Residual HIV-1 RNA and HIV-1 DNA production in the genital tract reservoir of
      women treated with HAART: the prospective ANRS EP24 GYNODYN study.
AB  - BACKGROUND: The female genital tract constitutes a reservoir for HIV providing
      active production of both cell-free HIV RNA and cell-associated DNA within the
      cervicovaginal secretions. The objective of this study was to prospectively
      assess residual HIV-1 RNA and HIV-1 DNA production in the genital tract reservoir
      of women initiating HAART over an 18-month period. METHODS: Paired blood and
      cervicovaginal lavage samples were collected at inclusion and 1, 6, 12 and 18
      months after HAART initiation, in 23 women in first-line HAART and six women in
      virological failure, for measurement of HIV-1 RNA and HIV-1 DNA shedding and/or
      drug concentrations. RESULTS: A dramatic decrease of HIV-1 RNA and HIV-1 DNA
      occurred in both blood and cervicovaginal samples over the first 6 months on
      HAART, followed by a shelf up to 18 months, independently of the drugs' genital
      pharmacokinetics. While cervicovaginal HIV-1 RNA became undetectable in >90% of
      women from 6 months on HAART, genital HIV-1 DNA remained frequently detectable
      (27-50%). Nearly 40% of women with sustained undetectable plasma HIV-1 RNA after
      6-18 months on HAART harboured transient HIV-1 RNA (15% of women) or HIV-1 DNA
      (31% of women) in their genital secretions. CONCLUSIONS: Low-level cervicovaginal
      HIV-1 shedding is frequently evidenced in HAART-treated women with transient HIV
      1 RNA and persistent HIV-1 DNA despite a systemic control of viral replication,
      resulting in possible residual genital infectivity.

PMID- 21900718
TI  - Long-term remission of recurrent herpes labialis following topical imiquimod
      application on distant healthy skin: a clinical and immunological study.
AB  - BACKGROUND: Given the limitations of current antiviral therapies, safer and more
      effective approaches to the management of recurrent herpes labialis (RHL) are
      needed. METHODS: A patient with a 23-year history of RHL and 14 healthy
      individuals were studied. The patient applied imiquimod to distant healthy skin
      for 3 weeks. Peripheral blood (PB) samples were collected from the patient during
      treatment and 21 months after its discontinuation; samples were collected from
      the controls once. The distribution of lymphocyte populations in PB were analysed
      by flow cytometry and PB cytokine levels were measured using cytometric bead
      arrays. RESULTS: The patient showed long-term remission of the disorder
      subsequent to a 3-week imiquimod application to distant healthy skin. Imiquimod
      treatment induced the activation and proliferation of T-helper and cytotoxic T
      cells, B-cells and T-regulatory cells. In addition, there was a very strong
      transient increase of T-helper 1 cells (resulting in interferon-gamma secretion)
      and type 1 (pro-inflammatory) polarization of the immune response accompanied by
      a sustainable interferon-alpha production. At follow-up 21 months after treatment
      cessation, with the patient remaining relapse-free, the patient had control
      levels of all cytokines, increased levels of activated cytotoxic T-cells,
      continuous production of new T-helper cells and B-cells and near-to-normal levels
      of T-regulatory cells. CONCLUSIONS: Our results indicate that topical application
      of imiquimod to healthy skin is capable of causing systemic immunomodulation.
      This treatment might represent a new and effective alternative to established
      therapeutic and prophylactic regimens for RHL.

PMID- 21900717
TI  - Early outcomes and the virological effect of delayed treatment switching to
      second-line therapy in an antiretroviral roll-out programme in South Africa.
AB  - BACKGROUND: More patients in resource-limited settings are starting second-line
      antiretroviral treatment (ART) following first-line ART failure. We aimed to
      describe predictors of lack of virological suppression in HIV-infected patients
      on second-line ART in a roll-out programme in South Africa. METHODS: A
      retrospective analysis was performed on an adult HIV treatment cohort who started
      second-line ART (lopinavir/ritonavir, didanosine and zidovudine) after
      virological failure of first-line ART (two consecutive HIV RNA>1,000 copies/ml).
      Predictors of week 24 lack of suppression (HIV RNA>400 copies/ml) on second-line
      ART were determined by bivariate analysis where missing equals failure. A
      multivariable model that adjusted for gender, age and time to ART switch was
      used. We tested these findings in sensitivity analyses defining lack of
      suppression at week 24 as HIV RNA>1,000 and >5,000 copies/ml. RESULTS: Of 6,339
      patients on ART, 202 started second-line ART. At week 24, an estimated 41% (95%
      CI 34-47) did not achieve virological suppression. Female sex (adjusted OR 2.25,
      95% CI 1.03-4.88) and time to ART switch (adjusted OR 1.07, 95% CI 1.01-1.14 for
      each additional month) increased the risk of lack of virological suppression.
      Age, CD4(+) T-cell count and HIV RNA at second-line ART initiation did not
      predict this outcome. In multivariate models, these findings were insensitive to
      the definition of lack of virological suppression. CONCLUSIONS: A substantial
      number of HIV-infected patients do not achieve virological suppression by week 24
      of second-line ART. Women and patients with delayed start of second-line ART
      after first-line ART failure were at an increased risk of lack of virological
      suppression.

PMID- 21900719
TI  - Next-generation sequencing of dried blood spot specimens: a novel approach to HIV
      drug-resistance surveillance.
AB  - BACKGROUND: HIV drug-resistance (DR) surveillance in resource-limited settings
      can be performed using dried blood spots (DBS) because of ease of collection,
      transportation and storage. Analysis of pooled specimens on next-generation
      sequencing (NGS)-based platforms, such as the 454 pyrosequencing, is an efficient
      sequencing method for determining HIV DR rates. In this study, we conducted HIV
      DR surveillance on DBS using NGS and identified minority variants in individual
      patients. METHODS: A total of 48 extracts of DBS from an HIV DR surveillance
      study in Mexico City were re-amplified using primers tagged with multiplex
      identifiers, pooled and pyrosequenced. Consensus sequences were generated for
      each specimen with mixtures identified at positions where >20% of the reads
      contained a variant. Individual consensus sequences were then analysed for DR
      mutations and compared with those derived from Sanger sequencing. RESULTS: DBS
      analysed with tagged pooled pyrosequencing (TPP) were highly concordant with
      Sanger sequencing genotypes from matching plasma and DBS (99.21% and 99.51%,
      respectively). An exception was an M184I mutation only detected with TPP of DBS
      at a frequency of 20.4%. Multiple specimens had minority variant reads below the
      20% mixture threshold. CONCLUSIONS: TPP using DBS is an effective method for HIV
      DR surveillance. TPP for genotyping results in cost savings of 40% over
      conventional in-house methods. The effect of low-abundance DR mutations,
      undetectable by conventional methods, remains to be determined. This technology
      might be applied to any HIV specimen (plasma/serum) and can also be used for
      other diagnostic assays where DNA sequencing is required.

PMID- 21900720
TI  - Ribavirin priming improves the virological response to antiviral treatment in
      transplanted patients with recurrent hepatitis C: a pilot study.
AB  - INTRODUCTION: Patients with hepatitis C recurrence after liver transplantation
      represent a clinical challenge. Antiviral treatment in transplant patients has
      usually poor tolerability and limited efficacy, with a mean sustained virological
      response (SVR) of 30%. Our pilot study was aimed at evaluating whether 8-week
      ribavirin pre-treatment could increase either adherence or antiviral effect of a
      48-week combination therapy. METHODS: Ribavirin pre-treatment (8 weeks) was
      started with 600 mg daily and increased to 10.4 mg/kg/day. After pre-treatment,
      1.5 MUg/kg/week pegylated interferon-alpha2b was added for 48 additional weeks of
      combination therapy. Blood count, liver function tests and plasma HCV-RNA were
      examined monthly. Ribavirin plasma concentrations were determined by HPLC.
      RESULTS: Thirteen patients (mean age 53+/-2 years, 11 males) were treated: eight
      were HCV genotype 1/4; five were genotype 2/3. The median baseline HCV RNA level
      was 6.5 log(10) (range 5.84-7.42 log(10)). During ribavirin pre-treatment the
      median HCV RNA levels decreased significantly (5.7 log(10) ; P=0.023). During
      combination therapy 6/13 (46%) patients exhibited a rapid virological response
      (RVR) and 10/13 (77%) patients a complete early virological response, two were
      non-responders. A decline of 0.5 log(10) HCV RNA during pre-treatment predicted
      RVR. SVR occurred in six patients (46%): four were genotype 2/3. Stable ribavirin
      dose reduction was required in only two patients (15%) in whom transient
      interferon reduction was also required. CONCLUSION: This proof-of-concept study
      indicates that ribavirin pre-treatment increased the tolerability of the
      antiviral treatment, and improved its efficacy in liver transplant patients.
      Moreover, the degree of HCV RNA decline during pre-treatment allowed one to
      predict on-treatment response.

PMID- 21900721
TI  - Abacavir coadministration does not interfere with the suppressive activity of
      ribavirin in an HCV replicon system.
AB  - BACKGROUND: HCV is a major cause of morbidity and mortality in HIV-coinfected
      patients. Several observational studies have suggested that HCV response to
      pegylated interferon and ribavirin is lower in HIV-coinfected patients treated
      with abacavir. It has been postulated that abacavir could compete with ribavirin
      to be phosphorylated, leading to a reduction in the active form of the drug
      (triphosphorylated ribavirin). Here, we studied the effect of abacavir, tenofovir
      or lamivudine addition on the suppressive activity of ribavirin in an HCV RNA
      replicon system. METHODS: We used the human hepatoma HuH-7 cell clone 9B
      containing the HCV genotype 1b replicon I389/NS3-3'. Cells were treated for 24 h
      with ribavirin (0, 10 and 50 MUM) plus abacavir, tenofovir or lamivudine at doses
      of 0, 10 and 50 MUM and HCV RNA production was quantified by real-time PCR in
      triplicate assays. Results were expressed as mean+/-SD of the HCV RNA produced
      per cell (log(10) IU/cell). Means were compared using the Student's t-test.
      RESULTS: Ribavirin treatment produced a dose-dependent suppression of HCV RNA
      production by the replicon system. Combination of ribavirin and interferon
      resulted in an additive antiviral activity. The addition of abacavir did not
      modify the suppressive activity of ribavirin on the replicon HCV RNA expression.
      Similar results were obtained when ribavirin was used in combination with
      tenofovir or lamivudine. CONCLUSIONS: In a subgenomic HCV RNA replicon system,
      the antiviral effect of ribavirin was not modified by the addition of abacavir,
      tenofovir or lamivudine.

PMID- 21900723
TI  - In vitro inhibition of feline leukaemia virus infection by synthetic peptides
      derived from the transmembrane domain.
AB  - BACKGROUND: The feline leukaemia virus (FeLV) is a gammaretrovirus commonly
      affecting cats. Infection with this virus often leads to fatal outcomes and, so
      far, no cure is available for this disease. Synthetic peptides with structures
      mimicking the transmembrane protein of the viral surface proteins hold the
      potential to effectively interfere with viral entry by hampering the fusion of
      viral and host cell membranes and constitute a novel approach for the treatment
      of infections with retroviruses. We identified and synthetically produced 11 FeLV
      peptides and evaluated their potential to block FeLV infection in vitro. METHODS:
      Cell cultures were exposed to FeLV subgroup A prior to the addition of the
      peptides. The inhibitory effect of the peptides was assessed by measuring FeLV
      gag protein in the supernatant of peptide versus mock-treated cell cultures using
      an ELISA. RESULTS: A peptide (EPK364) of 37 amino acids in length, with sequence
      homology to the HIV fusion inhibitor T-20, significantly suppressed viral
      replication by 88%, whereas no effects were found for shorter peptides. Two
      structurally modified variants of EPK364 also inhibited viral replication by up
      to 58% (EPK397) and 27% (EPK398). CONCLUSIONS: Our data support the
      identification of synthetic FeLV peptides that have the potential for a curative
      short-term therapy of viraemic cats. In addition, these peptides might become an
      important tool in xenotransplantation, where endogenous gammaretroviruses of the
      donor species might be able to infect the host.

PMID- 21900724
TI  - Hepatitis B surface antigen (HBsAg) decrease and serum interferon-inducible
      protein-10 levels as predictive markers for HBsAg loss during treatment with
      nucleoside/nucleotide analogues.
AB  - BACKGROUND: Hepatitis B surface antigen (HBsAg) loss is the ultimate goal of
      antiviral therapy and its prediction may be important for treatment
      individualization. Quantitative HBsAg (qHBsAg) has been shown to predict response
      to interferon-alpha, but few studies have analysed qHBsAg during treatment with
      nucleoside/nucleotide analogues (NAs). Serum interferon-inducible protein-10 (IP
      10) has been associated with treatment response in hepatitis C, but data in
      chronic hepatitis B are lacking. Here, we aimed to investigate potential factors
      predictive for HBsAg loss. METHODS: HBsAg was quantified at multiple time points
      in 126 patients with chronic HBV infection; 95 received NA treatment for 6-107
      months. At an early time point (first 6 months of therapy) and late time point
      after virological response (VR; HBV DNA<100 IU/ml), we distinguished three
      patterns of HBsAg decrease: strong decrease (>0.5 log(10)), moderate decrease
      (10% to 0.5 log(10)) and no decrease (<10%). In addition to conventional
      biochemical and virological parameters, we analysed serum IP-10 levels in 55
      patients. RESULTS: Early and late HBsAg kinetics did not correlate. Overall, 42%
      of patients with a strong HBsAg decrease 2 years after VR cleared HBsAg.
      Importantly, no patient without a late HBsAg decrease >0.5 log(10) cleared HBsAg.
      By contrast, early HBsAg decrease after 6 months of NA therapy was not associated
      with HBsAg loss. Baseline serum IP-10 levels were associated with late but not
      early HBsAg kinetics and were highest in patients with HBsAg loss. CONCLUSIONS:
      Monitoring qHBsAg after successful HBV DNA suppression might be useful to
      identify patients who clear HBsAg, implicating finite NA treatment. The role of
      IP-10 as predictive marker for HBsAg loss should be further evaluated.

PMID- 21900725
TI  - Prevalence of low-level HIV-1 variants with reverse transcriptase mutation K65R
      and the effect of antiretroviral drug exposure on variant levels.
AB  - BACKGROUND: It has been reported that treatment-naive individuals infected with
      HIV-1 subtype C may be more likely to harbour viral variants possessing a K65R
      reverse transcriptase gene mutation. The objectives of this study were to
      determine the prevalence of low-level K65R variants within different HIV-1
      subtypes and to assess the effects of antiretroviral exposure on K65R variant
      levels. METHODS: Treatment-naive individuals infected with different HIV-1
      subtypes were genotyped by ultra-deep sequencing. Samples were evaluated for low
      level variants to 0.4% or 1% levels depending upon viral load. Estimated
      mutational load was calculated by multiplying the percentage of the variant by
      the plasma viral load. RESULTS: A total of 411 treatment-naive individuals were
      evaluated by ultra-deep sequencing to 1% levels; 4 subjects (0.97%) had K65R
      variants at >=1% or had a very high mutation load. All four subjects had variants
      with linked drug resistance mutations suggesting transmitted resistant variants.
      147 ARV-naive subjects were sequenced to 0.4% levels; 8.8% (13/147) had K65R low
      level variants identified: 2.2% (2/92) in subtype B, 35.7% (10/28) in subtype C
      (P<0.001 for B versus C) and 3.7% (1/27) in non-B/C subtypes. The 13 ARV-naive
      subjects with K65R variants at <1% received tenofovir plus emtricitabine plus a
      ritonavir-boosted protease inhibitor (TDF+FTC+PI/r) and 5 subsequently
      experienced virological failure. There was no enhancement in K65R levels by
      percentage or mutational load compared to pre-therapy levels. CONCLUSIONS: Low
      level K65R variants were more frequently identified in subtype C. K65R variants
      at >1% levels likely represent transmitted resistant variants. The clinical
      implication of low-level K65R variants below 1% in treatment-naive subjects who
      receive TDF+FTC+PI/r remains to be determined as the majority are very low-level
      and did not increase after antiretroviral exposure.

PMID- 21900722
TI  - Insufficient antiretroviral therapy in pregnancy: missed opportunities for
      prevention of mother-to-child transmission of HIV in Europe.
AB  - BACKGROUND: Although mother-to-child transmission (MTCT) rates are at an all-time
      low in Western Europe, potentially preventable transmissions continue to occur.
      Duration of antenatal combination antiretroviral therapy (ART) is strongly
      associated with MTCT risk. METHODS: Data on pregnant HIV-infected women enrolled
      in the Western and Central European sites of the European Collaborative Study
      between January 2000 and July 2009 were analysed. The proportion of women
      receiving no antenatal ART or 1-13 days of treatment was investigated, and
      associated factors explored using logistic regression models. RESULTS: Of 2,148
      women, 142 (7%) received no antenatal ART, decreasing from 8% in 2000-2003 to 5%
      in 2004-2009 (chi(2)=8.73; P<0.01). A further 41 (2%) received 1-13 days of ART.
      One-third (64/171) of women with 'insufficient' (0 or 1-13 days) antenatal ART
      had a late HIV diagnosis (in the third trimester or intrapartum), but half
      (85/171) were diagnosed before conception. Pre-term delivery <34 weeks was
      associated with receipt of no and 1-13 days antenatal ART (adjusted odds ratios
      [ORs] 2.9 [P<0.01] and 4.5 [P<0.01], respectively). History of injecting drug use
      was associated with an increased risk of no ART (adjusted OR 2.9; P<0.01) and
      severe symptomatic HIV disease with a decreased risk (adjusted OR 0.2; P<0.01).
      MTCT rates were 1.1% (15/1,318) among women with >=14 days antenatal ART and 7.4%
      (10/136) among those with insufficient ART. CONCLUSIONS: Over the last 10 years,
      around one in 11 women in this study received insufficient antenatal ART,
      accounting for 40% of MTCTs. One-half of these women were diagnosed before
      conception, suggesting disengagement from care.

PMID- 21900726
TI  - Selection of an M184V mutation in the cerebrospinal fluid of a treatment-naive
      HIV-infected individual starting darunavir-based therapy.
AB  - Here, we describe a newly diagnosed HIV-1-infected patient, in whom shortly after
      the initiation of a darunavir-based regimen, the HIV-1 virus exclusively mutated
      in the cerebrospinal fluid (CSF), leading to an increase in CSF HIV-1 RNA load
      and neurological complaints.

PMID- 21900727
TI  - Long-lasting persistence of integrase resistance mutations in HIV-2-infected
      patients after raltegravir withdrawal.
AB  - BACKGROUND: Little is known in HIV-2 infection about the kinetics of
      disappearance of raltegravir (RAL)-resistant virus after RAL withdrawal. METHODS:
      RAL was interrupted in four highly antiretroviral-experienced HIV-2-infected
      patients exhibiting a virological failure when receiving RAL. Integrase gene was
      sequenced from plasma samples collected at the time of RAL failure and at further
      time points following RAL withdrawal. RESULTS: At the time of RAL withdrawal,
      virus exhibited different integrase resistance pathways: G140S/Q148R, E92Q/N155H,
      T97A/N155H and T97A/Y143C. In patient 1, the G140S/Q148R double-mutant was still
      detected at month (M)7 and at M11 after stopping RAL, but was no longer detected
      at M15. Regarding patient 2, the double-mutant E92Q/N155H was still present at M2
      and M8 after stopping RAL, and was no longer detected at M12. In patient 3, RAL
      resistant virus with T97A/N155H mutations were still present 1 month after
      stopping RAL, and were no longer detected at M14. Regarding patient 4, the mutant
      T97A/Y143C was still detected at M1 and M3 following RAL withdrawal. At M18 after
      RAL stop, integrase genotypic pattern evolved to T97A/Y143G. CONCLUSIONS:
      Persistence of HIV-2 RAL-resistant mutants was observed in all the key genetic
      RAL resistance pathways. These findings have clinical implications especially in
      HIV-2-infected patients for whom therapeutic arsenal is limited compared to HIV
      1, since the persistence of resistant mutants might compromise the possible
      efficacy of upcoming second-generation integrase inhibitors.

PMID- 21900728
TI  - The value of screening HIV-infected individuals for didanosine-related liver
      disease?

PMID- 21900729
TI  - Barriers to overcome for transition of breath tests from research to routine
      clinical practice.

PMID- 21900730
TI  - Three-dimensional inkjet biofabrication based on designed images.
AB  - Tissue engineering has been developed with the ultimate aim of manufacturing
      human organs, but success has been limited to only thin tissues and tissues with
      no significant structures. In order to construct more complicated tissues, we
      have developed a three-dimensional (3D) fabrication technology in which 3D
      structures are directly built up by layer-by-layer printing with living cells and
      several tissue components. We developed a custom-made inkjet printer specially
      designed for this purpose. Recently, this printer was improved, and the on-demand
      printing mode was developed and installed to fabricate further complicated
      structures. As a result of this version, 3D layer-by-layer printing based on
      complicated image data has become possible, and several 2D and 3D structures with
      more complexity than before were successfully fabricated. The effectiveness of
      the on-demand printing mode in the fabrication of complicated 3D tissue
      structures was confirmed. As complicated 3D structures are essential for
      biofunctional tissues, inkjet 3D biofabrication has great potential for
      engineering complicated bio-functional tissues.

PMID- 21900731
TI  - CAD/CAM-assisted breast reconstruction.
AB  - The application of computer-aided design and manufacturing (CAD/CAM) techniques
      in the clinic is growing slowly but steadily. The ability to build patient
      specific models based on medical imaging data offers major potential. In this
      work we report on the feasibility of employing laser scanning with CAD/CAM
      techniques to aid in breast reconstruction. A patient was imaged with laser
      scanning, an economical and facile method for creating an accurate digital
      representation of the breasts and surrounding tissues. The obtained model was
      used to fabricate a customized mould that was employed as an intra-operative aid
      for the surgeon performing autologous tissue reconstruction of the breast removed
      due to cancer. Furthermore, a solid breast model was derived from the imaged data
      and digitally processed for the fabrication of customized scaffolds for breast
      tissue engineering. To this end, a novel generic algorithm for creating porosity
      within a solid model was developed, using a finite element model as intermediate.

PMID- 21900732
TI  - The great challenge for exhaled breath analysis: embracing complexity, delivering
      simplicity.

PMID- 21900733
TI  - Single ion induced surface nanostructures: a comparison between slow highly
      charged and swift heavy ions.
AB  - This topical review focuses on recent advances in the understanding of the
      formation of surface nanostructures, an intriguing phenomenon in ion-surface
      interaction due to the impact of individual ions. In many solid targets, swift
      heavy ions produce narrow cylindrical tracks accompanied by the formation of a
      surface nanostructure. More recently, a similar nanometric surface effect has
      been revealed for the impact of individual, very slow but highly charged ions.
      While swift ions transfer their large kinetic energy to the target via ionization
      and electronic excitation processes (electronic stopping), slow highly charged
      ions produce surface structures due to potential energy deposited at the top
      surface layers. Despite the differences in primary excitation, the similarity
      between the nanostructures is striking and strongly points to a common mechanism
      related to the energy transfer from the electronic to the lattice system of the
      target. A comparison of surface structures induced by swift heavy ions and slow
      highly charged ions provides a valuable insight to better understand the
      formation mechanisms.

PMID- 21900734
TI  - The exchange bias phenomenon in uncompensated interfaces: theory and Monte Carlo
      simulations.
AB  - We performed Monte Carlo simulations of a bilayer system composed of two thin
      films, one ferromagnetic (FM) and the other antiferromagnetic (AFM). Two lattice
      structures for the films were considered: simple cubic and body centered cubic
      (bcc). We imposed an uncompensated interfacial spin structure in both lattice
      structures; in particular we emulated an FeF2-FM system in the case of the bcc
      lattice. Our analysis focused on the incidence of the interfacial strength
      interactions between the films, J(eb), and the effect of thermal fluctuations on
      the bias field, H(EB). We first performed Monte Carlo simulations on a
      microscopic model based on classical Heisenberg spin variables. To analyze the
      simulation results we also introduced a simplified model that assumes coherent
      rotation of spins located on the same layer parallel to the interface. We found
      that, depending on the AFM film anisotropy to exchange ratio, the bias field is
      controlled either by the intrinsic pinning of a domain wall parallel to the
      interface or by the stability of the first AFM layer (quasi-domain wall) near the
      interface.

PMID- 21900735
TI  - A magnetic Compton scattering study of Ga rich Co-Ni-Ga ferromagnetic shape
      memory alloys.
AB  - The temperature dependent spin momentum densities of Co(1.8)NiGa(1.2) and
      Co(2)Ni(0.76)Ga(1.24) alloys have been measured using the magnetic Compton
      scattering technique. The individual contributions of constituents in the
      formation of the total spin moment are also calculated using Compton line shape
      analysis. The magnetic Compton data when compared with the magnetization data
      obtained using a vibrating sample magnetometer show a negligible orbital
      contribution. The spin moments deduced from the experimental Compton data are
      compared with the theoretical results obtained from the full potential linearized
      augmented plane wave method and are found to be in good agreement. The origin of
      the magnetism in both alloys is also described in terms of the e(g) and t(2g)
      contributions of Ni and Co.

PMID- 21900736
TI  - Modulated spin waves and robust quasi-solitons in classical Heisenberg rings.
AB  - We investigate the dynamical behavior of finite rings of classical spin vectors
      interacting via nearest-neighbor isotropic exchange in an external magnetic
      field. Our approach is to utilize the solutions of a continuum version of the
      discrete spin equations of motion (EOM) which we derive by assuming continuous
      modulations of spin wave solutions of the EOM for discrete spins. This continuum
      EOM reduces to the Landau-Lifshitz equation in a particular limiting regime. The
      usefulness of the continuum EOM is demonstrated by the fact that the time-evolved
      numerical solutions of the discrete spin EOM closely track the corresponding time
      evolved solutions of the continuum equation. It is of special interest that our
      continuum EOM possesses soliton solutions, and we find that these characteristics
      are also exhibited by the corresponding solutions of the discrete EOM. The
      robustness of solitons is demonstrated by considering cases where initial states
      are truncated versions of soliton states and by numerical simulations of the
      discrete EOM equations when the spins are coupled to a heat bath at finite
      temperatures.

PMID- 21900737
TI  - Ideal shear strength under compression and tension in C, Si, Ge, and cubic SiC:
      an ab initio density functional theory study.
AB  - Ideal shear strength under superimposed normal stress of cubic covalent crystals
      (C, Si, Ge, and SiC) is evaluated by ab initio density functional theory
      calculation. Shear directions in [112] and [110] on the (111) plane are examined.
      The critical shear stress along the former direction is lower than that along the
      latter in all the crystals unless the hydrostatic tension is extremely high. In
      both the [112]-shear and [110]-shear, critical shear stress is increased by
      compression in C but is decreased in the other crystals. The different response
      of the critical shear stress to normal stress is due to the strength of the bond
      order term, i.e., dependence of the short-range interatomic attraction on the
      bond-angle.

PMID- 21900738
TI  - The effect of band Jahn-Teller distortion on the magnetoresistivity of
      manganites: a model study.
AB  - We present a model study of magnetoresistance through the interplay of
      magnetisation, structural distortion and external magnetic field for the
      manganite systems. The manganite system is described by the Hamiltonian which
      consists of the s-d type double exchange interaction, Heisenberg spin-spin
      interaction among the core electrons, and the static and dynamic band Jahn-Teller
      (JT) interaction in the e(g) band. The relaxation time of the e(g) electron is
      found from the imaginary part of the Green's function using the total Hamiltonian
      consisting of the interactions due to the electron and phonon. The calculated
      resistivity exhibits a peak in the pure JT distorted insulating phase separating
      the low temperature metallic ferromagnetic phase and the high temperature
      paramagnetic phase. The resistivity is suppressed with the increase of the
      external magnetic field. The e(g) electron band splitting and its effect on
      magnetoresistivity is reported here.

PMID- 21900739
TI  - Structural investigation of LaAlO3 up to 63 GPa.
AB  - We report a high-pressure synchrotron x-ray diffraction on a LaAlO(3) single
      crystal. The transition from rhombohedral to cubic at 14.8 GPa is confirmed by
      the loss of the superstructure reflections, whose intensity shows a linear
      pressure dependence, characteristic of a second-order transition. The crystal
      remains cubic up to 63 GPa, the highest pressure reached, which provides a
      confirmation over a very large pressure range of the general rules for the
      evolution of distortions of perovskites under pressure. We report the parameters
      of the Birch-Murnaghan equations of state in the low- and high-pressure phases
      and discuss the evolution of the bulk modulus.

PMID- 21900740
TI  - Auxin efflux transporter MtPIN10 regulates compound leaf and flower development
      in Medicago truncatula.
AB  - Plant diversity in nature is to a large extent reflected by morphological
      diversity of their leaves. Both simple and dissected (with multiple blades or
      leaflets) leaves are initiated from shoot apical meristem (SAM) in a highly
      ordered fashion. Similarly, development of leaflets from leaf marginal meristem
      (marginal blastozone) is also highly ordered. How morphological diversity of
      plant leaves is regulated remains an important topic of studies on plant form
      evolution. Here, we describe isolation and characterization of loss-of-function
      mutants of auxin efflux transporter MtPIN10 of a legume species, Medicago
      truncatula. Mtpin10 mutants exhibit defects in diverse developmental processes
      including leaf and leaflet development. Cross species genetic complementation
      demonstrates that MtPIN10 and Arabidopsis PIN1 are functional orthologs. Double
      mutant analyses reveal complex genetic interactions between MtPIN10 and Medicago
      SINGLE LEAFLET1 (SGL1), and CUP-SHAPED COTYLEDON2 (MtCUC2), three regulatory
      genes involved in developmental processes including dissected leaf and flower
      development. 

PMID- 21900741
TI  - Transcriptome analysis of Arabidopsis thaliana plants in response to kin and
      stranger recognition.
AB  - Recent reports have demonstrated that Arabidopsis thaliana has the ability to
      alter its growth differentially when grown in the presence of secretions from
      other A. thaliana plants that are kin or strangers, however, little knowledge has
      been gained as to the physiological processes involved in these plant-plant
      interactions. Therefore, we examined the root transcriptome of A. thaliana plants
      exposed to stranger versus kin secretions to determine genes involved in these
      processes. We conducted a whole transcriptome analysis on root tissues and
      categorized genes with significant changes in expression. Genes from four
      categories of interest based on significant changes in expression were identified
      as ATP/GST transporter, auxin/auxin related, secondary metabolite and pathogen
      response genes. Multiple genes in each category were tested and results indicated
      that pathogen response genes were involved in the kin recognition response.
      Plants were then infected with Pseudomonas syringe pv. Tomato DC3000 to further
      examine the role of these genes in plants exposed to own, kin and stranger
      secretions in pathogen resistance. This study concluded that multiple
      physiological pathways are involved in the kin recognition. The possible
      implication of this study opens up a new dialogue in terms of how plant-plant
      interactions change under a biotic stress.

PMID- 21900742
TI  - Constitutive expression of MKS1 confers susceptibility to Botrytis cinerea
      infection independent of PAD3 expression.
AB  - Signal transduction through MAPK cascades is essential for eukaryotic cell
      response to various extracellular stimuli, such as the induction of innate immune
      responses. Arabidopsis thaliana relies in particular on three of its 20 MAPKs,
      MPK3,-4,-6, for a proper immune response. Recently we showed that one MPK4
      substrate, MKS1, is required for basal resistance against the virulent
      Pseudomonas syringae and the oomycete Hyaloperonospora arabidopsidis.
      Overexpression of MKS1 (35S-MKS1) led to increased resistance to the same
      pathogens but also to an increased susceptibility towards the fungi Botrytis
      cinerea. MKS1 interacts with the transcription factor WRKY33, which in turn
      controls the regulation of PAD3 and CYP71A13, two genes, required for proper
      resistance to B. cinerea. Therefore, we tested if the increased susceptibility
      towards B. cinerea from 35S-MKS1 was due to deregulation of WRKY33 targets. PAD3
      and CYP71A13 expression is similar in 35S-MKS1 and WT after B. cinerea treatment
      suggesting another mechanism controls 35S-MKS1 susceptibility.

PMID- 21900743
TI  - Acetylcholine promotes the emergence and elongation of lateral roots of Raphanus
      sativus.
AB  - Radish (Raphanus sativus L.) was grown on four layers of paper towel moistened
      with distilled water with and without acetylcholine (ACh) for five days in the
      dark after sowing. ACh at 1 nM promoted the growth (emergence and elongation) of
      lateral roots of radish plants, but had no effect on the stems and main roots.
      Moreover, ACh enhanced the dry weight of roots [main (primary) + lateral roots].
      Neostigmine, an inhibitor of acetylcholinesterase (AChE) also promoted the
      emergence and elongation of lateral roots, and atropine, a competitive inhibitor
      of ACh receptor, suppressed the emergence and elongation. ACh suppressed the
      activity of AChE and increased the amount of proteins and pyridine nucleotides
      (NAD and NADH) in the roots of the seedlings. It also increased the activities of
      NAD-forming enzymes [NAD synthetase and ATP-nicotinamide mononucleotide (ATP-NMN)
      adenyltransferase], and enhanced the amount of DNA in the roots of the seedlings.
      The relationship between ACh and the emergence and growth of lateral roots was
      discussed from a biochemical viewpoint.

PMID- 21900744
TI  - SIRT6 overexpression induces massive apoptosis in cancer cells but not in normal
      cells.
AB  - Emerging evidence suggests that Sirtuin 6 (SIRT6) functions as a longevity
      assurance gene by promoting genomic stability, regulating metabolic processes and
      attenuating inflammation. Here, we examine the effect of SIRT6 activation on
      cancer cells. We show that SIRT6 overexpression induces massive apoptosis in a
      variety of cancer cell lines but not in normal, non-transformed cells. This cell
      death requires the mono-ADP-ribosyltransferase but not the deacetylase activity
      of SIRT6 and is mediated by the activation of both the p53 and p73 apoptotic
      signaling cascades in cancer cells by SIRT6. These results suggest that SIRT6 is
      an attractive target for pharmacological activation in cancer treatment.

PMID- 21900745
TI  - Linear polyubiquitin chains: a new modifier involved in NFkappaB activation and
      chronic inflammation, including dermatitis.
AB  - The ubiquitin conjugation system regulates a wide variety of biological
      phenomena, including protein degradation and signal transduction, by regulating
      protein function via polyubiquitin conjugation in most cases. Several types of
      polyubiquitin chains exist in cells, and the type of polyubiquitin chain
      conjugated to a protein seems to determine how that protein is regulated. We
      identified a novel linear polyubiquitin chain and the ubiquitin-protein ligase
      complex that assembles it, designated LUBAC. Both were shown to have crucial
      roles in the canonical NFkappaB activation pathway. This year, three groups,
      including our laboratory, identified SHARPIN as a new subunit of LUBAC. Of great
      interest, Sharpin was identified as a causative gene of chronic proliferative
      dermatitis in mice (cpdm), which is characterized by numerous inflammatory
      symptoms including chronic dermatitis, arthritis and immune disorders. Deletion
      of SHARPIN drastically reduces the amount of LUBAC and attenuates signal-induced
      NFkappaB activation. The pleomorphic symptoms of cpdm mice suggest that LUBAC
      mediated NFkappaB activation may play critical roles in mammals and be involved
      in various disorders. A forward look into the linear polyubiquitin research is
      also discussed.

PMID- 21900746
TI  - C086, a novel analog of curcumin, induces growth inhibition and down-regulation
      of NFkappaB in colon cancer cells and xenograft tumors.
AB  - New analogues of curcumin with improved properties are needed to meet therapeutic
      requirements. In this study, the effects of C086 on growth inhibition and
      NFkappaB pathway regulation were investigated in colon cancer cells and xenograft
      tumors. C086 exhibited potent antiproliferative activity in all 6 colon cancer
      cell lines. In a xenograft model of SW480 cells in nude mice, the oral
      administration of C086 showed significant growth suppression of SW480 tumors, and
      both Western blot and immunohistochemistry analyses showed decreased NFkappaB
      (p65) expression in tumor tissues. Using TNF-alpha to induce NFkappaB activation
      in SW480 cells, it was revealed that C086 inhibited IkappaBalpha phosphorylation
      and its subsequent degradation, and suppressed the nuclear translocation and DNA
      binding activity of NFkappaB. C-Myc, cyclin D1, and Bcl-2, NFkappaB-regulated
      gene products involving in cellular proliferation and antiapoptosis, were
      decreased in the C086 treated groups. This effect was accompanied by pro
      apoptosis of C086 in colon cancer cells and lower expression of PCNA in C086
      treated colon cancer xenografts. Immunostaining for CD31 showed that there were
      fewer microvessels in C086 treated SW480 tumors, and NFkappaB-targeted gene
      products involved in angiogenesis (i.e., vascular endothelial growth factor,
      matrix metalloproteinase-9) were also downregulated. C086 also inhibited bovine
      aortic endothelial cell (BAEC) proliferation and tube formation in Matrigel.
      Overall, our results suggest that C086 is a potent antitumor agent and has
      promising future in colon cancer. C086 suppressed NFkappaB activation through
      inhibition of IkappaBalpha phosphorylation. Downregulation of NFkappaB-regulated
      gene products contributed to the antiproliferation, pro-apoptosis, and
      antiangiogenesis effect of C086.

PMID- 21900748
TI  - The tumor suppressor tuberin regulates mitotic onset through the cellular
      localization of cyclin B1.
AB  - Tuberous sclerosis is a multi-organ disorder characterized by the formation of
      benign tumors, called hamartomas, which affects more than 1 million people
      worldwide. The syndrome is initiated by a mutation in one of two tumor suppressor
      genes, TSC1 or TSC2, that encode for the proteins hamartin and tuberin,
      respectively. Herein, we demonstrate that tuberin binds and regulates the G 2/M
      cyclin, cyclin B1. We have determined that this binding region encompasses a
      mutational hotspot within tuberin that is implicated in some of the most severe
      cases of TS. Mimicking a mutation found in a subset of patients with tuberous
      sclerosis, we found a significant reduction in the binding between tuberin and
      cyclin B1. Functionally, our data supports that tuberin plays a role in
      regulating the cellular localization of cyclin B1. These results demonstrate a
      novel and clinically relevant mechanism, where tuberin functions in mitotic
      onset.

PMID- 21900747
TI  - Schedule-dependent synergy of histone deacetylase inhibitors with DNA damaging
      agents in small cell lung cancer.
AB  - Small cell lung cancer (SCLC) is an aggressive lung cancer subtype in need of
      better therapies. Histone deacetylase inhibitors (HDIs) promote increased lysine
      acetylation in nucleosomal histones and are thought to relax chromatin, thereby
      allowing increased access of transcription factors and DNA damaging agents alike
      to DNA. We studied whether two HDIs, belinostat and romidepsin, could be
      effectively combined with cisplatin or etoposide (VP-16) for SCLC cells. Analysis
      of cell survival and synergy was performed using CalcuSyn mathematical modeling
      to calculate a combination index. Immunostaining of gammaH2AX was performed to
      evaluate persistence of DNA damage following simultaneous or sequential exposure.
      Based on CalcuSyn modeling, HDIs synergized with DNA damaging agents only when
      added simultaneously. An additive-to-antagonistic effect was seen with HDI
      pretreatment for 24 h or with addition after cisplatin or etoposide. Furthermore,
      pretreatment with HDIs resulted in normalization of cell cycle and reduced PARP
      degradation as compared with simultaneous treatment. The increase in gammaH2AX
      phosphorylation confirmed that simultaneous but not sequential treatment enhanced
      double-stranded DNA breaks. These results suggest that DNA relaxation is not
      required for synergy of HDIs with DNA damaging agents, and that scheduling of
      drug administration will be critical for rational development of clinical
      protocols.

PMID- 21900749
TI  - A GSK-3-mediated transcriptional network maintains repression of immediate early
      genes in quiescent cells.
AB  - Glycogen synthase kinase-3 (GSK-3) plays a central role in cell survival and
      proliferation, in part by the regulation of transcription. Unlike most protein
      kinases, GSK-3 is active in quiescent cells in the absence of growth factor
      signaling. In a recent series of studies, we employed a systems-level approach to
      understanding the transcription network regulated by GSK-3 in a quiescent cell
      model. We identified a group of immediate early genes that were upregulated in
      quiescent cells solely by the inhibition of GSK-3 in the absence of growth factor
      stimulation. Computational analysis of the upstream sequences of these genes
      identified statistically over-represented binding sites for the transcription
      factors CREB, NFkappaB and AP-1, and the roles of these factors in regulating
      expression of GSK-3 target genes were verified by chromatin immunoprecipitation
      and RNA interference. In quiescent cells, GSK-3 inhibits CREB, NFkappaB and AP-1,
      thereby maintaining repression of their target genes and contributing to
      maintenance of cell cycle arrest.

PMID- 21900751
TI  - Raptor, a positive regulatory subunit of mTOR complex 1, is a novel
      phosphoprotein of the rDNA transcription machinery in nucleoli and chromosomal
      nucleolus organizer regions (NORs).
AB  - Raptor is the key scaffolding protein that recruits mTOR substrates to rapamycin
      sensitive mTOR complex 1 (mTORC1), a molecular integrator of mitogenic and
      nutrient/energy environmental inputs into protein translation and cell growth.
      Although Raptor phosphorylation on various sites is pivotal in the regulation of
      mTORC1 activity, it remains to be elucidated whether site-specific
      phosphorylation differentially distributes Raptor to unique subcellular
      compartments. When exploring the spatiotemporal cell cycle dynamics of six
      different phospho (P)-Raptor isoforms (Thr ( 706) , Ser ( 722) , Ser ( 863) , Ser
      ( 792)  and Ser ( 877) ), a number of remarkable events differentially defined a
      topological resetting of P-RaptorThr706 on interphasic and mitotic chromosomes.
      In interphase nuclei, P-Raptor (Thr706)  co-localized with fibrillarin, a
      component of the nucleolar small nuclear ribonucleoprotein particle, as well as
      with RNA polymerase I, the enzyme that transcribes nucleolar rRNA. Upon
      Actinomycin D-induced nucleolar segregation and disaggregation, P-RaptorThr706
      was excluded from the nucleolus to accumulate at discrete nucleoplasmic bodies.
      During mitosis, CDK1 inhibition-induced premature assembly of nucleoli relocated
      fibrillarin to the surrounding regions of chromosomal-associated P-Raptor
      (Thr706) , suggesting that a subpopulation of mitotic P-Raptor (Thr706)  remained
      targeted at chromosomal loops of rDNA or nuclear organizer regions (NORs). At the
      end of mitosis and cytokinesis, when reassembly of incipient nucleoli begins upon
      NORs activation of rDNA transcription, fibrillarin spatially reorganized with P
      Raptor (Thr706)  to give rise to daughter nucleoli. Treatment with IGF1
      exclusively hyperactivated nuclear P-Raptor (Ser706)  and concomitantly promoted
      Ser ( 2481)  autophosphorylation of mTOR, which monitors mTORC1-associated
      catalytic activity. Nucleolar- and NOR-associated P-Raptor (Ser706)  may
      physically link mTORC1 signaling to ever-growing nucleolus plurifunctionality
      including ribosome biogenesis, cell stress sensor and cell cycle/aging control.

PMID- 21900750
TI  - Network calisthenics: control of E2F dynamics in cell cycle entry.
AB  - Stimulation of quiescent mammalian cells with mitogens induces an abrupt increase
      in E2F1-3 expression just prior to the onset of DNA synthesis, followed by a
      rapid decline as replication ceases. This temporal adaptation in E2F facilitates
      a transient pattern of gene expression that reflects the ordered nature of DNA
      replication. The challenge to understand how E2F dynamics coordinate molecular
      events required for high-fidelity DNA replication has great biological
      implications. Indeed, precocious, prolonged, elevated or reduced accumulation of
      E2F can generate replication stress that culminates in either arrest or death.
      Accordingly, temporal characteristics of E2F are regulated by several network
      modules that include feedforward and autoregulatory loops. In this review, we
      discuss how these network modules contribute to "shaping" E2F dynamics in the
      context of mammalian cell cycle entry.

PMID- 21900753
TI  - Mesenchymal stem cell-secreted soluble signaling molecules potentiate tumor
      growth.
AB  - In previous studies, we and others have shown that bone marrow mesenchymal stem
      cells (MSCs) are recruited to sites of growing tumors and promote tumor growth in
      mouse xenograft models, suggesting that interactions between MSCs and tumor cells
      may play an important role in this process. However, the exact mechanism remains
      unclear. In the present study, we investigated whether the physical presence or
      the continuous presence of MSCs is required for enhanced tumor growth, and we
      found that pretreatment of tumor cells SGC-7901 with a single dose of human MSC
      conditioned medium (hMSC-CM) in vitro is sufficient to potentiate tumor growth
      comparable to the effect of MSC co-injection in vivo in mouse xenograft models.
      We further showed that significant tumor modifying activity is present in post
      ultracentrifigation soluble fraction. Biochemical analysis suggests that hMSC-CM
      induces the expression of VEGF of tumor cells as well as the activation of RhoA
      GTPase and ERK1/2. Furthermore, hMSC-CM-enhanced tumor growth is sustainable in
      serial transplantation, suggesting that MSC-secreted factors have profound
      effects on "reprogramming" of tumor growth. Our data provide new insights into
      the way in which MSCs modify tumor growth and offer a new and exciting
      opportunity to develop effective therapeutics for intercepting tumor progression.

PMID- 21900755
TI  - Cataract surgery: from couching to femtosecond, look how far we have come!

PMID- 21900756
TI  - Bibliography. Cataract surgery and lens implantation. Current world literature.

PMID- 21900759
TI  - Forty-eight years with duchenne muscular dystrophy.

PMID- 21900752
TI  - MDM2 promotes SUMO-2/3 modification of p53 to modulate transcriptional activity.
AB  - The tumor suppressor p53 is extensively regulated by post-translational
      modification, including modification by the small ubiquitin-related modifier
      SUMO. We show here that MDM2, previously shown to promote ubiquitin, Nedd8 and
      SUMO-1 modification of p53, can also enhance conjugation of endogenous SUMO-2/3
      to p53. Sumoylation activity requires p53-MDM2 binding but does not depend on an
      intact RING finger. Both ARF and L11 can promote SUMO-2/3 conjugation of p53.
      However, unlike the previously described SUMO-1 conjugation of p53 by an MDM2-ARF
      complex, this activity does not depend on the ability of MDM2 to relocalize to
      the nucleolus. Interestingly, the SUMO consensus is not conserved in mouse p53,
      which is therefore not modified by SUMO-2/3. Finally, we show that conjugation of
      SUMO-2/3 to p53 correlates with a reduction of both activation and repression of
      a subset of p53-target genes.

PMID- 21900760
TI  - Ultrasound-guided injection of the piriformis muscle.

PMID- 21900761
TI  - 'Pure' partial trisomy 11q (11q23.1->11qter): expanding the phenotype.

PMID- 21900763
TI  - Editorial comment.

PMID- 21900764
TI  - Current world literature.

PMID- 21900766
TI  - Trends in antimicrobial resistance in intensive care units in the United States.
AB  - PURPOSE OF REVIEW: Antimicrobial resistance and a paucity of new antimicrobial
      agents are ongoing challenges. This review focuses on the major epidemiologic
      trends and novel treatments, when available, for methicillin-resistant
      Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus, Clostridium
      difficile, and multidrug-resistant Gram-negative bacilli in the United States
      during 2010-2011. RECENT FINDINGS: MRSA bloodstream infection rates have
      declined, primarily due to interventions aimed at decreasing vascular catheter
      infections. The proportion of MRSA due to the community-associated strain USA300
      continues to increase. Recent studies of active surveillance and contact
      isolation for MRSA prevention provide conflicting views of efficacy. Two novel
      treatments for recurrent C. difficile infection, monoclonal antibodies and
      fidaxomicin, show promising results. Antimicrobial resistance among Gram-negative
      bacilli has become widespread; extended-spectrum beta-lactamases are now commonly
      found among Escherichia coli causing community-acquired infections in the United
      States. Klebsiella pneumoniae carbapenemases have spread beyond the northeast,
      and the New Delhi metallo-beta-lactamase has been reported in multiple countries
      within a few years of its discovery. SUMMARY: Antimicrobial resistance,
      particularly among Gram-negative bacilli, continues to increase at a rapid rate.
      Given the frequent transfer of patients between outpatient and acute care
      settings, as well as between different geographic regions, coordinated infection
      control interventions are warranted.

PMID- 21900767
TI  - Current insights in sepsis: from pathogenesis to new treatment targets.
AB  - PURPOSE OF REVIEW: Sepsis continues to be a leading cause of ICU death. This
      review summarizes current knowledge on sepsis pathogenesis and new therapeutical
      strategies. RECENT FINDINGS: Although systemic inflammatory response syndrome
      predominates in early sepsis, the compensatory anti-inflammatory response
      syndrome causes immunosuppression associated with late mortality. Toll-like
      receptors (TLR), the inflammasomes and other pattern-recognition receptors (PRR)
      initiate the host response after recognition of invading pathogens and endogenous
      danger signals. The TLR-regulated pro-inflammatory cytokines macrophage migration
      inhibitory factor and high-mobility-group-box-1 protein are promising treatment
      targets. Controversy on intensive insulin therapy, steroids, and activated
      protein C in sepsis has led to a re-evaluation of these immunomodulatory
      strategies. Interestingly, the anticoagulant protein C also exerts cytoprotective
      effects by neutralizing extracellular DNA. Endotoxin removal devices, TLR4
      inhibitors, and restoration of sepsis-induced immunosuppression are other
      strategies being evaluated in sepsis patients. SUMMARY: Sepsis can be seen as a
      PRR-mediated dysregulation of the immune system following pathogen invasion in
      which a careful balance between inflammatory and anti-inflammatory responses is
      vital. Detailed knowledge of host response pathways and new approaches in sepsis
      trial design, which take into account patient heterogeneity and the phase of the
      immunological response, represent major steps forward in sepsis research.

PMID- 21900768
TI  - Probiotics for prevention of nosocomial infections: efficacy and adverse effects.
AB  - PURPOSE OF REVIEW: In this era of increasing antimicrobial resistance, use of
      probiotics in infection prevention has brought new perspective. However, in 2008
      the, until then considered, safe use of probiotics became an important topic
      after publication of a trial showing excess mortality in patients on probiotic
      prophylaxis. In this article, we review the concept of infection prevention by
      probiotics and the present knowledge of the efficacy of probiotics in prevention
      of infections among patients with abdominal diseases and in intensive care.
      Safety issues of probiotics will be discussed extensively. RECENT FINDINGS: Over
      30 clinical trials with probiotics to prevent infections have been published,
      some of which were prematurely stopped recently. Studies with critically ill
      patients and patients with abdominal diseases showed conflicting results
      regarding the effects of probiotics on infection rates, as did meta-analyses.
      These studies are difficult to compare because different probiotics were used
      which all have different efficacy and safety profiles. SUMMARY: The efficacy of
      probiotics in infection prevention among critically ill patients is still not
      unequivocally determined. The safety profile differs per probiotic strain and
      should not be generalized towards other strains and patient populations. A well
      designed and well powered clinical trial with clear endpoints to demonstrate
      efficacy is warranted.

PMID- 21900769
TI  - Understanding health economic analysis in critical care: insights from recent
      randomized controlled trials.
AB  - PURPOSE OF REVIEW: The article reviews the methods of health economic analysis
      (HEA) in clinical trials of critically ill patients. Emphasis is placed on the
      usefulness of HEA in the context of positive and 'no effect' studies, with recent
      examples. RECENT FINDINGS: The need to control costs and promote effective
      spending in caring for the critically ill has garnered considerable attention due
      to the high cost of critical illness. Many clinical trials focus on short-term
      mortality, ignoring costs and quality of life, and fail to change clinical
      practice or promote efficient use of resources. Incorporating HEA into clinical
      trials is a possible solution. Such studies have shown some interventions,
      although expensive, provide good value, whereas others should be withdrawn from
      clinical practice. Incorporating HEA into randomized controlled trials (RCTs)
      requires careful attention to collect all relevant costs. Decision trees,
      modeling assumptions and methods for collecting costs and measuring outcomes
      should be planned and published beforehand to minimize bias. SUMMARY: Costs and
      cost-effectiveness are potentially useful outcomes in RCTs of critically ill
      patients. Future RCTs should incorporate parallel HEA to provide both economic
      outcomes, which are important to the community, alongside patient-centered
      outcomes, which are important to individuals.

PMID- 21900770
TI  - Health-related quality of life: implications for critical care interventional
      studies and why we need to collaborate with patients.
AB  - PURPOSE OF REVIEW: Health-related quality of life (HRQoL) is an important patient
      reported outcome measure following critical illness. 'Validated' and
      professionally endorsed generic measures are widely used to evaluate critical
      care intervention and guide practice, policy and research. Although recognizing
      that they are 'here to stay', leading QoL researchers are beginning to question
      their 'fitness for purpose'. It is therefore timely to review critiques of their
      limitations in the wider healthcare and social science literatures and to examine
      the implications for critical care research including, in particular, emerging
      interventional studies in which HRQoL is the primary outcome of interest. RECENT
      FINDINGS: Generic HRQoL measures have provided important yet limited insights
      into HRQoL among survivors of critical illness. They are rarely developed or
      validated in collaboration with patients and cannot therefore be assumed to
      reflect their experiences and perspectives. SUMMARY: Collaboration with patients
      is advocated in order to improve the interpretation and utility of such data.
      Failure to do so may result in important study effects being overlooked and the
      dismissal of potentially useful interventions.

PMID- 21900771
TI  - Current world literature.

PMID- 21900773
TI  - Current world literature.

PMID- 21900775
TI  - Current world literature.

PMID- 21900777
TI  - Impact areas in pediatric transplantation.

PMID- 21900778
TI  - Current world literature.

PMID- 21900780
TI  - Mechanism of valvular regurgitation.
AB  - PURPOSE OF REVIEW: Despite improvements in surgical techniques, valvular
      regurgitation results in major morbidity in children with heart disease.
      Functional anatomy, mechanisms of valve closure and adaptation to changing
      hemodynamic stress in normal mitral and tricuspid valves are complex and only
      partially understood. As well, pathology of atrioventricular valve regurgitation
      is further complicated by congenital valve abnormalities involving leaflet
      tissue, supporting chordal apparatus and displaced papillary muscles. This review
      provides a current understanding of the mechanisms that result in
      atrioventricular valve failure. RECENT FINDINGS: Mitral valve leaflets have
      contractile elements, in addition to atrial muscle modulation of leaflet tension.
      When placed under mechanical tethering stress, the mitral valve adapts by leaflet
      expansion, which increases coaptation surface reserve and chordal thickening.
      Both pediatric and adult studies are increasingly reporting on the importance of
      subvalvar apparatus function in maintaining valve competency. SUMMARY: The
      maintenance of efficient valve function is accomplished by a complex series of
      events involving atrial and annular contraction, annular deformation, active
      leaflet tension, chordal transmission of papillary muscle contractions and
      ventricular contraction.

PMID- 21900781
TI  - Health-related quality of life in cystic fibrosis.
AB  - PURPOSE OF REVIEW: To review the contribution of various therapeutic
      interventions on both longevity and quality of life in cystic fibrosis patients.
      RECENT FINDINGS: Long-term survival in cystic fibrosis has increased markedly in
      the past 25 years, largely due to a robust clinical trials program carried out at
      Cystic Fibrosis Foundation accredited clinical centers in the United States and
      similar organizations worldwide. Cystic fibrosis patients are recommended
      complex, time-intensive daily therapies that are often difficult for families and
      patients to sustain long-term. Recently, attention to the perceived value of a
      particular therapy on a patient's well being is recognized as important for
      individualizing therapeutic regimens that provide maximal clinical benefit and
      are more likely to be adhered to long-term by the patient. Cystic fibrosis care
      is in a new era in which patient-related outcomes (PROs) for the assessment of
      health-related quality of life (HRQOL) are regarded with equal importance to
      medically beneficial therapies. SUMMARY: Numerous advances in the clinical care
      of cystic fibrosis have led to improved survival, although definitive correction
      of the abnormal cystic fibrosis transmembrane regulator protein function remains
      elusive. Patients struggle to maintain rigorous, time-intensive therapeutic
      regimens, whereas clinicians strive to identify which interventions preserve
      quality of life. Cystic fibrosis patients depend on their caregiver's ability to
      assess both the medical benefit and the contribution to quality of life that
      therapeutic regimes bring to their disease. Caregivers, in turn, need measures of
      HRQOL in order to prioritize the various therapeutic interventions that are at
      their disposal in order to provide not just longevity, but meaningful quality of
      life.

PMID- 21900782
TI  - The role of growth hormone and insulin-like growth factor-1 in Crohn's disease:
      implications for therapeutic use of human growth hormone in pediatric patients.
AB  - PURPOSE OF REVIEW: This review evaluates the role of the growth hormone (GH) and
      insulin-like growth factor (IGF) in influencing linear growth in pediatric
      Crohn's disease. It also examines the current evidence concerning the use of
      recombinant human growth hormone (rhGH) as a potential therapy in achieving
      optimal growth and inducing mucosal healing for pediatric Crohn's disease. RECENT
      FINDINGS: Current treatment strategies for Crohn's disease including antitumor
      necrosis factor-alpha (TNF-alpha) therapy have been demonstrated to improve
      growth velocity, but linear growth deficits persist despite optimization of
      therapy. By complex mechanisms, including the reduction of levels of IGF-1 and
      induction of systemic and hepatic GH resistance, cytokines such as TNF-alpha and
      interleukin-6 (IL-6), commonly elevated in active Crohn's disease, are important
      as mediators of linear growth delay. Recent evidence suggests that rhGH therapy
      is effective in improving short-term linear growth for a selected group of
      patients but of limited benefit as a therapy for improving mucosal disease and
      reducing clinical disease activity. SUMMARY: Crohn's disease interacts with the
      GH-IGF-1 axis in important ways. Recent studies evaluating rhGH use in pediatric
      Crohn's disease have demonstrated some efficacy in reversing persistent linear
      growth delay but limited benefits in terms of improving mucosal disease and
      clinical disease activity. Larger studies of adequate power are needed to confirm
      a true benefit in terms of growth, to examine a potential benefit with regard to
      modification of disease activity, and to evaluate long-term risks.

PMID- 21900783
TI  - Current world literature.

PMID- 21900784
TI  - Does BMI affect the clinical efficacy of proton pump inhibitor therapy in GERD?
      The case for rabeprazole.
AB  - BACKGROUND: Increased BMI is associated with a higher risk of gastroesophageal
      reflux disease. AIMS: To investigate whether overweight/obesity (BMI>=25 kg/m(2))
      affects rabeprazole clinical efficacy versus omeprazole in patients with erosive
      esophagitis (EE). PATIENTS AND METHODS: Post-hoc analysis of EE healing rate and
      symptom response stratified by patient BMI was performed on data from a
      multicenter, double-blind, randomized, 4-to-8-week trial comparing EE healing
      with rabeprazole (20 mg daily) and omeprazole (20 mg daily). Analysis of
      variance, two-sample t-test, Blackwelder's test for equivalence, log-rank, and
      Cochran-Mantel-Haenszel tests were used to analyze comparisons. RESULTS: In the
      two BMI groups (<25 kg/m(2) and >=25 kg/m(2) respectively), rabeprazole and
      omeprazole were equally effective for mucosal healing regardless of patient's BMI
      (N=542, P>0.05). However, in overweight/obese patients, rabeprazole was
      significantly faster than omeprazole in inducing heartburn relief during the
      first treatment week (P<0.0001). CONCLUSIONS: Results of this study show that the
      clinical efficacy of rabeprazole is maintained in overweight/obese patients with
      gastroesophageal reflux disease and suggest that this subgroup of patients may
      derive, from rabeprazole, even greater benefit than lean patients.

PMID- 21900785
TI  - Meta-analysis: cyclooxygenase-2 inhibitors are no better than nonselective
      nonsteroidal anti-inflammatory drugs with proton pump inhibitors in regard to
      gastrointestinal adverse events in osteoarthritis and rheumatoid arthritis.
AB  - OBJECTIVE: To compare cyclooxygenase-2 (Cox-2) inhibitors alone with NSAIDs plus
      proton pump inhibitors (PPIs) in preventing gastrointestinal adverse events:
      upper gastrointestinal (UGI) adverse events and gastrointestinal symptoms in
      Osteoarthritis and Rheumatoid arthritis. METHODS: PubMed, the Cochrane Library,
      EMBASE, ISI Web of Knowledge, Chinese Biomedical Literature Database, and
      reference lists of relevant papers for articles published 1990-2010.12 were
      searched. The related data matching standards set for this study were extracted.
      Statistical analyses were carried out using RevMan (5.0) software. RESULTS: The
      meta-analysis of six randomized controlled trials with a total of 6219 patients
      revealed that there was no difference in the UGI adverse events between Cox-2
      inhibitors and nonselective NSAIDs with concurrent use of PPIs [relative risk
      (RR) 0.61, 95% confidence interval (CI) 0.34-1.09]. There was no significant
      difference in gastrointestinal symptoms (RR 1.10, 95% CI: 0.88-1.39) and the
      cardiovascular adverse events (RR 1.67, 95% CI: 0.78-3.59) between the two
      groups. CONCLUSION: Cox-2 inhibitors are no better than nonselective NSAIDs with
      PPIs in regard to UGI adverse events, gastrointestinal symptoms and
      cardiovascular adverse events in Osteoarthritis and Rheumatoid arthritis. On the
      basis of the current evidence and the combined wishes of the patient, clinicians
      should carefully consider and weigh both gastrointestinal and cardiovascular risk
      before selecting NSAID plus PPIs or Cox-2 inhibitors.

PMID- 21900786
TI  - Preparation before colonoscopy: a randomized controlled trial comparing different
      regimes.
AB  - BACKGROUND AND AIM: A good bowel preparation is essential for optimal
      visualization of the large intestine. Several preparations with a difference in
      composition and volume are available. We compared five methods for bowel
      cleansing quality and patients' acceptability. PATIENTS AND METHODS: Adult
      ambulatory outpatients scheduled for elective colonoscopy were randomized to
      receive 4-l polyethylene glycol (PEG) solution (Klean-prep), 2-l PEG
      solution+ascorbic acid (Moviprep), or a sodium phosphate (NaP) solution,
      Phosphoral. Patients with the PEG solutions were also randomized to receive
      simethicone (Aeropax), to investigate whether this improves the bowel cleansing
      efficacy. Before colonoscopy patients completed a questionnaire about the
      acceptability and tolerability of the preparation. Endoscopists blinded to the
      type of preparation gave a bowel cleansing score. RESULTS: Data were available
      for 461 patients. 2-l PEG+ascorbic acid was noninferior to 4-l PEG in bowel
      cleansing quality of rectosigmoid and colon. NaP was noninferior to 4-l PEG in
      bowel cleansing quality of rectosigmoid but inferior for the whole colon.
      Compliance was significantly less in the group with 4-l PEG compared with the 2-l
      PEG and NaP group. No difference was found for abdominal cramps. Taste was
      significantly better in the 2-l PEG group. Simethicone did not improve the bowel
      cleansing quality. CONCLUSION: 2-l PEG+ascorbic acid was noninferior to the 4-l
      PEG solution in bowel cleansing quality and was better in taste and compliance.
      NaP was inferior to 4-l PEG in bowel cleansing quality. Addition of simethicone
      gave no improvement.

PMID- 21900787
TI  - A single IL28B genotype SNP rs12979860 determination predicts treatment response
      in patients with chronic hepatitis C Genotype 1 virus.
AB  - BACKGROUND: Recent studies have suggested that host genetics may be useful for
      predicting drug response and have supported the recommendation that single
      polynucleotide polymorphisms (SNPs) of IL28B should be investigated when treating
      hepatitis C virus (HCV)-1 infected patients. The aim of this study was to
      determine whether a single IL-28B genotype SNP rs8099917 or rs12979860
      determination is sufficient to predict treatment failure in patients with chronic
      HCV. METHODS: A total of 198 patients were included; mean (+/-standard deviation)
      age was 47+/-12 years and 140 (71%) were men. One hundred and fifty-six (79%)
      patients were infected with HCV genotype 1 and 42 (21%) with HCV genotypes 2 or
      3. One hundred and eight (55%) patients had sustained virologic response (SVR).
      Two SNPs in the IL-28B were analyzed (rs8099917 and rs12979860). RESULTS: A total
      of 115 (58%) patients had rs8099917 TT genotype and 61 (31%) had rs12979860 CC
      genotype. Rs8099917 TT and rs12979860 CC genotypes were associated with SVR in
      HCV genotype 1 patients [odds ratio=2.60 (1.36-5.00), P=0.004 and odds ratio=3.30
      (1.58-6.90), P=0.03 respectively]. No association was found between SNPs and SVR
      in HCV genotype 2 or 3 patients. CONCLUSION: This study confirms that SNPs
      rs8099917 and rs12979860 used alone may be useful for predicting the outcome of
      HCV treatment. In a rational and cost-effective approach, determination of only
      one of these two SNPs is sufficient for predicting SVR. Because of the highest
      predictive SVR associated with rs12979860 CC compared with the rs8099917 TT
      (respective positive predictive value: 72% vs. 63%, P=ns), rs12979860
      determination alone is sufficient for predicting interferon response.

PMID- 21900788
TI  - Clinical and laboratory evaluation of patients with end-stage liver cell failure
      injected with bone marrow-derived hepatocyte-like cells.
AB  - AIM: One of the defining features of the liver is the capacity to maintain a
      constant size despite injury. Extrahepatic stem cells especially bone marrow
      derived stem cells are thought to undertake an important role in liver
      repopulation. This study was carried out to evaluate the outcome of autologous
      bone marrow-derived hepatocytes transplantation in patients with end-stage liver
      cell failure due to chronic hepatitis C. METHODS: Forty patients were included,
      divided into two groups. Group I: 20 patients receiving autologous bone marrow
      derived mesenchymal stem cells stimulated to hepatic lineage. They were
      subdivided into two groups regarding the route of transplantation: intrasplenic
      (10) and intrahepatic (10). Group II: included 20 patients who received
      traditional supportive treatment. Patients were followed up using examination,
      laboratory investigations, abdominal ultrasonography, and evaluated by Child
      score, Model for End Stage Liver Disease score, fatigue scale, and performance
      status. RESULTS: The results showed significant improvement in group I regarding
      ascites, lower limb edema, and serum albumin, over the control group. Group I
      also showed statistically significant improvement in Child score, Model for End
      Stage Liver Disease score, fatigue scale, and performance status over the
      controls. No difference was observed between intrahepatic and intrasplenic
      groups. CONCLUSION: This study demonstrated the safety and short-term efficacy of
      autologous bone marrow-derived mesenchymal stem cell injection in liver cell
      failure. Further study is necessary to standardize the cell dose, determine the
      life span of the injected cells, and detect the appearance of long-term
      complications.

PMID- 21900789
TI  - Metastatic cutaneous Crohn's disease of the face: a case report and review of the
      literature.
AB  - Metastatic cutaneous Crohn's disease is one of the most uncommon cutaneous
      extraintestinal manifestations. The face is the rarest location, with only eight
      cases described in the literature. We report a rare case of a young man with
      Crohn's disease and two granulomatous lesions on the face in a nodular form. To
      the best of our knowledge, this is the first report of metastatic Crohn's disease
      of the forehead with the features of nodules. A review of the literature
      concerning metastatic Crohn's disease is also provided.

PMID- 21900791
TI  - Are we entering a new era in melanoma treatment? Lesson from ASCO 2011.

PMID- 21900793
TI  - Differentiation of melanoma and benign nevi by fluorescence in-situ
      hybridization.
AB  - Malignant melanoma is sometimes difficult to distinguish from benign nevus, and
      ancillary confirmatory studies would be of value in selected cases. To accurately
      differentiate melanoma from benign nevus, we investigated the utility of
      chromosomal anomalies in skin biopsy specimens using multitargeted fluorescence
      in-situ hybridization (FISH). Skin biopsy specimens were retrospectively
      collected from 63 patients diagnosed with benign compound nevus (n=32) or
      malignant melanoma (n=31); each diagnosis was independently confirmed before
      study by a second dermatopathologist. Unstained tissue sections were hybridized
      for 30 min using fluorescence-labeled oligo-DNA probes for chromosomes 6, 7, 11,
      and 20. Fluorescent signals for each chromosome were enumerated in 30 cells per
      case. Numeric chromosomal anomalies were found in 0% (0 of 32) of normal
      epidermis, 6% (two of 32) of compound nevi, and 94% (29 of 31) of melanomas
      (nevus vs. melanoma, P<0.0001). The mean number of cells with chromosomal changes
      was 23 in melanoma specimens, significantly higher than that in compound nevi
      (P<0.0001). The most frequent chromosomal anomaly in melanoma was gain of
      chromosome 11, followed consecutively by gains of chromosomes 7, 20, and 6.
      Chromosomal anomalies detected by FISH had an overall sensitivity of 94% and
      specificity of 94% in the separation of nevus and melanoma. With the use of oligo
      DNA probes, multitargeted FISH directed against chromosomes 6, 7, 11, and 20 is
      highly sensitive and specific for separation of nevus and melanoma. Unlike other
      traditional FISH probes, oligo-DNA probes required shorter hybridization time,
      allowing faster diagnostic evaluation.

PMID- 21900792
TI  - Expression of CD133 and other putative stem cell markers in uveal melanoma.
AB  - 'Cancer stem cells' (CSCs) are tumor cells with stem cell properties hypothesized
      to be responsible for tumorigenesis, metastatis, and resistance to treatment, and
      have been identified in different tumors including cutaneous melanoma, using stem
      cell markers such as CD133. This study explored expression of CD133 and other
      putative stem cell markers in uveal melanoma. Eight uveal melanoma cell lines
      were subjected to flow-cytometric (fluorescence-activated cell sorting) analysis
      of CD133 and other stem cell markers. Eight paraffin-embedded tumors were
      analyzed by immunohistochemistry for CD133, Pax6, Musashi, nestin, Sox2, ABCB5,
      and CD68 expressions. Ocular, uveal melanoma, and hematopoietic stem cell
      distributions of C-terminal and N-terminal CD133 mRNA splice variants were
      compared by reverse-transcription PCR. Fluorescence-activated cell sorting
      analysis revealed a population of CD133-positive/nestin-positive cells in cell
      lines Mel270, OMM 2.3, and OMM2.5. All cell lines studied were positive for
      nestin, CXCR-4, CD44, and c-kit. Immunohistochemistry identified cells positive
      for CD133, Pax6, Musashi, nestin, Sox2, ABCB5, and CD68 predominantly at the
      invading tumor front. C-terminal primers interacting with CD133 splice variant s2
      detected a novel variant lacking exon 27. Differential expression of CD133 splice
      variants was found in iris, ciliary body, retina, and retinal pigment
      epithelium/choroid as well as in uveal melanoma cell lines. mRNA for nestin,
      Sox2, and Musashi was present in all studied cell lines. Uveal melanoma such as
      cutaneous melanoma may therefore contain CSCs. Further experiments are needed to
      isolate stem cell marker-positive cells, to evaluate their functional properties
      and to explore therapeutical approaches to these putative CSCs in uveal melanoma.

PMID- 21900799
TI  - The experience of pain and the putamen: a new link found with functional MRI and
      diffusion tensor imaging.

PMID- 21900800
TI  - Progress in sequencing human cancer genomes: advancements in childhood
      medulloblastoma.

PMID- 21900801
TI  - HIF-1alpha potentiates mesenchymal stem cell mediated osteogenesis by coupling to
      angiogenesis.

PMID- 21900802
TI  - More nurses means fewer inpatient deaths.

PMID- 21900803
TI  - Restructuring of multidisciplinary scientific meetings improves valuable exchange
      of information.

PMID- 21900804
TI  - Changing neural networks with brain machine interfaces-neuronal firing
      adaptations to BMI learning.

PMID- 21900805
TI  - Guidelines or individualized medicine: can they be reconciled?

PMID- 21900806
TI  - Differential expression of pluripotency factors Sox2 and Oct4 regulate neuronal
      and mesenchymal lineages.

PMID- 21900807
TI  - Exposing conflicts of interest and complications of rhBMP-2.

PMID- 21900808
TI  - Glioblastoma multiforme stem-like cells and hypoxia: the novel role of HAF.

PMID- 21900809
TI  - Differential scanning calorimetry applied to cerebrospinal fluid analysis in
      glioblastoma.

PMID- 21900811
TI  - Executive nurse educational preparation.

PMID- 21900812
TI  - What nursing leaders must master...

PMID- 21900810
TI  - Postoperative infection may influence survival in patients with glioblastoma:
      simply a myth?
AB  - BACKGROUND: It is a prevalent myth that a postoperative infection may actually
      confer a survival advantage in patients with malignant glioma. This contention is
      based largely on anecdotal reports. Recently, a single-center study showed there
      was no survival advantage in those patients who had glioblastoma with
      postoperative infection. OBJECTIVE: To examine the impact of postoperative
      infections on outcome in patients with glioblastoma treated at our center.
      METHODS: This study included 197 patients with newly diagnosed primary
      glioblastoma treated from January 2001 to January 2008. Of the 197 patients, 10
      (5.08%) had postoperative bacterial infection. The Kaplan-Meier method, log-rank
      test, and Breslow test were used in the univariate approach; Cox regression was
      used in the multivariable approach. RESULTS: The median survival was 16 months
      (95% confidence interval [CI], 14-18 mo). The infection group had a significant
      advantage in the median survival: 30 months (95% CI, 21-39) vs 15 months (95% CI,
      13-17) for patients without postoperative infection. This advantage was also
      confirmed by Cox regression; in fact, patients not developing a postoperative
      infection showed an adjusted hazard ratio for death of 2.3 (95% CI, 1-5.3).
      CONCLUSION: The association between infection and prolonged survival is not
      definitive; we acknowledge the considerable difficulties in undertaking this type
      of study in a retrospective manner. Our results can instead stimulate further
      multicentric studies (to increase the number of patients) or experimental studies
      using genetically modified bacteria for treatment of glioblastoma.

PMID- 21900813
TI  - Back to the future: learning from the past to prepare competent nurse leaders for
      the future. Interview by Franklin A. Shaffer.
AB  - If today's need for highly competent nurse leaders is urgent, and there seems to
      be no controversy about this fact, what will be the need in the next few years?
      And what will ensure the availability of these highly competent persons? Between
      the opportunities offered by the Accountable Care Act, and the IOM Report on the
      Future of Nursing's recommendations, the consensus is that the need will be
      great. This is not a new concern: During the 1960s, the pendulum in graduate
      education in nursing swung from functional preparation in teaching, supervision,
      and administration to clinical specialization. While the change was a logical
      one, inadequate consideration was given to the preparation of people who would
      fill these roles in the real world. Consequently, Boston University School of
      Nursing held an invitational conference in 1978 to respond to the call for
      preparation of competent nursing leaders. The author interviews some of the
      leaders who attended and/or presented at this conference to see just how much we
      could learn for the past to apply today.

PMID- 21900814
TI  - Innovations in academic and practice partnerships: new collaborations within
      existing models.
AB  - New models in academic institutions that engage practice experts accelerate
      innovative thinking, productivity, and quality. A successful model in a southwest
      university college of nursing and health innovation is presented. In this
      article, the authors provide experiences specific to identifying needs,
      developing partnerships, integrating experts into the college, and challenges in
      sustaining partnerships and their potential for transforming the academic and
      service relationship in the age of reform.

PMID- 21900815
TI  - Developing nurse leaders: a program enhancing staff nurse leadership skills and
      professionalism.
AB  - This study aims to determine whether participation in the Nursing Leadership
      Perspectives Program (NLPP) at Mayo Clinic in Rochester, Minnesota, produced a
      change in leadership skills, increased professional activities, leadership
      promotion, and retention rates of participants. The NLPP is an educational
      program designed to enhance leadership skills and promote professionalism of
      registered nurses. The 6-month program provides participants with theoretical
      knowledge, core competencies, and opportunities to practice application of
      leadership skills. Outcome metrics were collected from registered nurses who
      completed the program (n = 15). Data analysis included descriptive and
      nonparametric methods. Participants reported statistically significant changes in
      their leadership skills after participation in the program (P = .007) on the
      Leadership Practices Inventory. Changes in professional behavior were also
      statistically significant as rated by the Nursing Activity Scale (P = .001).
      Participants demonstrated a change in leadership skills and professional behavior
      following the program.

PMID- 21900816
TI  - Developing the leadership skills of new graduates to influence practice
      environments: a novice nurse leadership program.
AB  - The authors of the recently published Institute of Medicine on the Future of
      Nursing report emphasized the importance of preparing nurses to lead change to
      advance health care in the United States. Other scholars linked practice
      environments to safe quality care. In order for nurses to fully actualize this
      role in practice environments, they need to possess leadership skills sets that
      identify and respond to challenges faced. New nurses are no exception. This
      article presents a program with a 5-year track record that is designed to support
      transition and enhance the skill sets of leadership for new nurses in their first
      year of practice. Qualitative and quantitative evaluation measurements at
      baseline and postprogram provided data for evaluation of the first 4 cohorts in
      the program. Evaluative outcomes presented indicate that new nurses gained
      leadership and translational research skills that contributed to their ability to
      influence practice environments. Nonetheless, practice environments continue to
      need improvement and ongoing leadership from all levels of nursing must be
      upheld.

PMID- 21900817
TI  - Advancing nursing leadership: a model for program implementation and measurement.
AB  - Despite the abundant literature documenting the need for nurse management
      education and career development, only recently have professional standards been
      targeted for this group. Competency standards for nurse leaders repeatedly
      identify systems-level concepts including finance and budget, communication
      skills, strategic management, human resources management, change management, and
      computer technology skills. However, educational initiatives to meet these
      standards are still at the early stages and most nurse leaders continue to
      acquire knowledge and experience through "on-the-job" training. This article will
      illustrate the need for partnerships and collaboration between academia and
      hospitals to advance nursing leadership to the next century. In addition, a tool
      to measure the impact of a graduate certificate program in nursing administration
      on nurse leader competencies is presented. Overall, the certificate program has
      been successful in multiple ways; it has "graduated" almost 80 nurse leaders,
      improved participant competence in their role at the systems level, as well as
      providing an impetus for completion of a graduate degree post program.

PMID- 21900818
TI  - Beyond the classroom: nurse leader preparation and practices.
AB  - Formal academic education and experience as a nurse are established preparation
      for the chief nurse executive (CNE) or upcoming nurse leaders. This article
      proposes that the nurse leader must build on these fundamentals through self
      discipline, lifelong learning, and practice. Three critical ingredients are
      discussed to guide the nurse leader on a life/career for the CNE and the nurse
      leader at every level. These include fostering relationships, feeding
      intellectual curiosity, and engaging in self-care practices. These indispensable
      ingredients of the successful nurse leader serve as an augmentation to formal
      education and experience for the nurse aspiring to reach the CNE level and beyond
      as well as for the current CNE mentoring future leaders.

PMID- 21900819
TI  - Creating insight when the literature is absent: the circle of advisors.
AB  - When changes happen as rapidly as they do today, the literature is often absent.
      Although related literature may be available to substantiate a direction to take
      when faced with some issue to resolve, that literature may be vague in terms of
      its applicability within health care. The idea of a circle of advisors was
      instituted to gain insight from experts who had faced similar challenges and
      often had extensive networks of shared experiences. The use of a sequential
      dialog identified specific talents to be developed in a chief nurse executive
      enculturation program.

PMID- 21900820
TI  - Chief nursing officer executive development: a crisis or a challenge?
AB  - The roles and responsibilities of nurses are expanding, as they become more
      involved in administration and leadership within their field. Nurses are taking
      on executive positions, which have become a crucial part of hospital
      organizations. With this expansion, an executive development program is necessary
      to provide nurses with the knowledge and competencies that these executive
      positions require. Their focus must evolve from singular bedside practice to the
      greater scope of health care administration. Leadership skills are extremely
      important, in addition to interpersonal, management, mentoring, and
      interprofessional skills. A number of nursing associations have worked to develop
      a set of curricula for nurse executive education, but a consistent and specific
      set of academic requirements has yet to be agreed upon. With the importance of
      the chief nursing officer's (CNO) role in the function of a hospital and the
      requirement of the knowledge of the changing health care system in the United
      States, it is essential that nurses are provided with proper education and
      training that will help them become successful nurse executives. Some suggestions
      include a dual MSN/MBA degree, a PhD in nursing, continuing education institutes,
      and mentoring programs. However, research must be done to clarify the best way to
      prepare CNOs for their roles.

PMID- 21900821
TI  - Global nursing leadership: a practical guide.
AB  - Nursing leaders of today must be prepared for a nursing practice environment
      inclusive of local, national, and global work and issues. The educational
      preparation of nursing leaders should incorporate a fundamental curriculum that
      offers a broad preparation and basic leadership skills along with guidelines and
      experiences to support global outreach and collaboration with many cultures and
      health care environments. This article provides a practical guide on entry into
      Global Nursing Leadership for nursing leaders from the nurse executive including
      all levels of nursing management.

PMID- 21900822
TI  - Regulation 101 for the nurse administrator.

PMID- 21900823
TI  - News from the front.

PMID- 21900824
TI  - Maternal exposure to unexpected economic contraction and birth weight for
      gestational age.
AB  - BACKGROUND: The macro-level economy may affect fetal health through maternal
      behavioral or physiologic responses. METHODS: We used a multilevel design to
      examine associations between exposure to state-level unexpected economic
      contraction during each trimester of gestation and birth weight for gestational
      age percentile and small for gestational age (SGA), using the National
      Longitudinal Survey of Youth 1979. We examined differences in observed
      associations by maternal educational attainment, race/ethnicity, employment
      status, and poverty status. RESULTS: Exposure in the first trimester was
      associated with a 3.7 percentile point decrease in birth weight for gestational
      age (95% confidence interval [CI] = -6.8 to -0.6). This association appeared
      stronger for women "keeping house" or with <12 years education. Exposure in the
      first trimester was also associated with increased odds of SGA (odds ratio = 1.5
      [95% CI = 1.1 to 2.1]) and term SGA (odds ratio = 1.6 [95% CI = 1.2 to 2.3]).
      CONCLUSIONS: Unexpected economic contraction during early pregnancy may be
      associated with reduced fetal growth.

PMID- 21900825
TI  - Does antidepressant use attenuate the risk of a major depressive episode in
      pregnancy?
AB  - BACKGROUND: Many women become pregnant while undergoing antidepressant treatment
      and are concerned about continuing antidepressant medication. However,
      antidepressant discontinuation may increase the risk of a new episode of major
      depressive disorder. We sought to estimate differences in the risk of developing
      a new major depressive episode among pregnant and postpartum women with recurrent
      illness who either did or did not use antidepressants. METHODS: Participants were
      recruited from obstetrical settings; we analyzed a subgroup of 778 women with a
      history of a depressive disorder. Diagnoses were determined by the Composite
      International Diagnostic Interview administered twice in pregnancy and once after
      delivery. We used Cox Regression to model onset of a major depressive episode
      with a time-dependent predictor of antidepressant use. RESULTS: There was no
      clear difference in risk of a major depressive episode between women who took
      antidepressants and women who did not (hazard ratio [HR] = 0.88; 95% CI = 0.51
      1.50). After accounting for antidepressant use, clearly hazardous factors
      included 4 or more depressive episodes before pregnancy (HR = 1.97; 95% CI = 1.09
      3.57), black race (HR = 3.69; 95% CI = 2.16-6.30), and Hispanic ethnicity (HR =
      2.33; 95% CI = 1.47-3.69). CONCLUSIONS: Failure to use or discontinuation of
      antidepressants in pregnancy did not have a strong effect on the development of a
      major depressive episode. Women with 4 or more episodes before pregnancy were at
      high risk of a major depressive episode, independent of antidepressant use. Black
      and Hispanic women also were at high risk of a major depressive episode, but it
      is possible that this effect is attributable to unmeasured factors.

PMID- 21900826
TI  - Sex and race differences in the prevalence of fatty liver disease as measured by
      computed tomography liver attenuation in European American and African American
      participants of the NHLBI family heart study.
AB  - BACKGROUND AND AIMS: Liver attenuation (LA) [Hounsfield Units (HU)] by computed
      tomography is a validated quantitative measure that is inversely related to liver
      fat burden. We examined race and sex differences on the distribution of LA [one
      of the first stages of fatty liver disease (FLD)] and the predictors of these
      mean differences in European American (EA) and African American (AA) participants
      of the Family Heart Study. MATERIALS AND METHODS: A total of 1242 (1064 EA, 178
      AA) and 1477 (1150 EA, 327 AA) men and women, respectively, underwent computed
      tomography examination from which LA and abdominal adipose volume were measured.
      LA (adjusted for phantom and field center) was the dependent variable in linear
      mixed models (to control for family relatedness) that tested for mean differences
      by race and by sex. Independent explanatory variables included age, BMI, visceral
      adipose tissue volume (VAT), subcutaneous adipose tissue volume, alcohol
      consumption, triglyceride, HDL-cholesterol, and insulin resistance. RESULTS: Mean
      LA varied significantly by sex, [(men) 57.76+/-10.03 HU and (women) 60.03+/-10.91
      HU, P=0.0002], but not by race. Higher LA was associated with older age, whereas
      higher values of VAT, triglycerides, and insulin resistance were associated with
      lower LA in men and women. In contrast, alcohol consumption and BMI were
      associated with lower LA only among men. In analyses stratified by race, LA was
      associated with alcohol consumption, VAT, and insulin resistance in both EA and
      AA and with age, BMI, and HDL-cholesterol in EA participants only. CONCLUSIONS:
      Our study findings confirm that there are important sex differences and race by
      sex interaction effects on the distribution of LA, the prevalence of FLD, and on
      the influence of metabolic risk factors on LA and FLD.

PMID- 21900827
TI  - The concept of bootstrapping of structural equation models with smaller samples:
      an illustration using mealtime rituals in diabetes management.
AB  - OBJECTIVE: The objective of this study was to offer a practical demonstration of
      the use of bootstrapping in structural equation modeling (SEM) with smaller
      samples by evaluating family dinnertime rituals at the intersection between the
      family social environment and pediatric type 1 diabetes mellitus management.
      METHOD: Participants were 77 children and adolescents aged 6 to 18 years and
      their mothers from a larger study of child and parental challenges related to
      managing the treatment regimen and correlates of adherence. SEM was used to test
      a model of maternal reports of the family social environment as exogenous
      variables with mealtime rituals and child hemoglobin A1c levels as endogenous
      variables. The bootstrapping procedure and the Bollen-Stine bootstrapped chi test
      were then applied to test the stability and appropriateness of this model.
      RESULTS: Using SEM, the final model had robust goodness-of-fit indicators and
      revealed that the family social environment characteristics of control and
      cohesion were related to mealtime rituals, which was associated with hemoglobin
      A1c levels. The bootstrapping procedure indicated that the parameter estimates
      were very stable, thus lending greater credence to the model. The Bollen-Stine
      approach provided evidence that the entire hypothesized model was not
      significantly different from the model derived from bootstrapping. CONCLUSIONS:
      This investigation offers a practical demonstration of the bootstrapping
      technique and the Bollen-Stine approach for testing models on smaller samples in
      SEM. These techniques may be used with relatively small samples, which are common
      in developmental/behavioral pediatrics and pediatric psychology research.

PMID- 21900828
TI  - Developmental coordination disorder in school-aged children born very preterm
      and/or at very low birth weight: a systematic review.
AB  - OBJECTIVE: : To systematically review and synthesize the literature to document
      the association between infants born very preterm and/or very low birth weight
      (VLBW) and the presence of developmental coordination disorder (DCD) at school
      age. METHODS: : Seven databases were systematically searched. Studies were
      included if they examined very preterm (<32 weeks) and/or VLBW (<1500 g) infants
      to school age (age, 5-18 years), had a full-term and/or normal birth weight
      comparison group, and used a formal measure of motor impairment. Studies that
      included only infants who were small for gestational age or diagnosed with
      cerebral palsy were excluded. Two independent reviewers completed abstract and
      full-text screening, data extraction, and quality assessment of included studies.
      RESULTS: : Sixteen articles were included, with 7 studies incorporated into 2
      meta-analyses using cutoff scores of either <5th or 5-15th percentile on the
      Movement Assessment Battery for Children. Both analyses showed a significant
      increase in the likelihood of DCD for children born very preterm and/or 1500 g or
      less, with odds ratios of 6.29 (95% confidence interval, 4.37-9.05, p < .00001)
      and 8.66 (95% confidence interval, 3.40-22.07, p < .00001) for <5th or 5-15th
      percentile scores, respectively. CONCLUSIONS: : Consistent across studies, DCD is
      more prevalent in the VLBW/very preterm population than full-term/normal birth
      weight control children and the general school-age population, with significantly
      greater odds of developing the disorder. Clinical practice should focus on early
      identification of and intervention for children with DCD, while research should
      focus on determining the mechanisms underlying DCD in the preterm population.

PMID- 21900829
TI  - Effective out-of-operating room airway management for physicians not
      traditionally trained in airway management.
AB  - BACKGROUND: There is a dearth of literature about the safety and practicality of
      intubation performed by an internal medicine (IM) or any other nonanesthesia,
      nonemergency physician. OBJECTIVES: The objectives of the study were to describe
      abbreviated airway management training guidelines for IM physicians staffing the
      emergency department and to compare the success rates between intubations
      performed by anesthesia and IM physicians, respectively. METHODS: In this study,
      272 consecutive out-of-operating room intubations performed by anesthesia and IM
      physicians were evaluated after creating and implementing an abbreviated
      intubation training protocol. RESULTS: Of 165 intubations attempted by IM
      physicians and 107 intubations attempted by the anesthesia service, the rates of
      successful intubation were 93% and 99%, respectively (P = 0.02). There were no
      other statistically significant differences in outcomes. CONCLUSIONS:
      Procedurally oriented IM fellows could provide a temporary solution to hospitals
      that currently do not have the resources to provide full-time, in-house
      anesthesiology or emergency physicians for management of the emergent airway.

PMID- 21900830
TI  - Monitoring of anti-transglutaminase autoantibodies in pediatric celiac disease
      using a sensitive radiobinding assay.
AB  - OBJECTIVES: The diagnosis of celiac disease (CD) is based on the histological
      identification of gluten-sensitive enteropathy and detection of anti-tissue
      transglutaminase antibodies (tTGA) and/or endomysial antibodies. Serial
      measurements of tTGA are now recommended as a follow-up strategy to monitor
      compliance with a gluten-free diet (GFD). We evaluated the performances of a
      quantitative radiobinding assay (RBA) of tTGA immunoglobulin A at diagnosis and
      during monitoring of GFD in pediatric CD. METHODS: Eighty children with confirmed
      CD were selected. Levels of serum tTGA measured by RBA and a commercial enzyme
      linked immunosorbent assay (ELISA) were compared at diagnosis. The relation
      between RBA-tTGA levels and histological damage was analyzed, as well as the time
      course of tTGA clearance during GFD. RESULTS: Both RBA and ELISA showed high
      sensitivity and specificity for tTGA detection at diagnosis. There was no
      relation between RBA-tTGA levels at diagnosis and severity of mucosal damage.
      Upon initiation of GFD, the rate of RBA-tTGA positivity declined slower than that
      of endomysial antibodies positivity, with >50% of the children still tTGA
      positive at year 5; however, tTGA levels decreased rapidly during the first year
      of GFD and more slowly thereafter. Children who seroreverted had lower tTGA
      levels at diagnosis (2080+/-1554 cpm) than those who remained tTGA positive
      throughout follow-up (3688+/-1435 cpm). CONCLUSIONS: The high sensitivity of RBA
      is likely responsible for higher tTGA positivity rates during GFD than previously
      reported with ELISA. A decreasing trend for tTGA levels may represent a better
      surrogate marker of compliance with GFD than absolute normal tTGA levels.

PMID- 21900831
TI  - Biliary atresia:  new lessons learned from the past.

PMID- 21900832
TI  - Dysmegakaryopoiesis, a clue for an early diagnosis of familial platelet disorder
      with propensity to acute myeloid leukemia in case of unexplained inherited
      thrombocytopenia associated with normal-sized platelets.
AB  - We report dysmegakaryopoiesis in a case of familial platelet disorder with
      predisposition to acute myeloid leukemia (familial platelet disorder/acute
      myeloid leukemia phenotype Mendelian Inheritance in Man number 601 399). Slight
      reduction of the number of megakaryocytes with high nucleocytoplasmic ratio,
      strongly basophilic cytoplasm and poorly lobulated nuclei are suggestive of
      megakaryocytic dysplasia.

PMID- 21900833
TI  - Methemoglobinemia in postchemotherapy stomatitis topical treatment: 2 pediatric
      cases.
AB  - Methemoglobinemia is a rare congenital or acquired disease of increased blood
      methemoglobin concentration. We documented 2 cases of children suffering from
      neuroblastoma whose postchemotherapy anemia, leucopenia, and stomatitis were
      complicated by methemoglobinemia after using a formulary oral gel (7.5%
      benzocaine, doxycycline, nystatin, glycerin). The complication resulted in
      hospital treatment. Percutaneous oxygen saturation remained at 85% and 87%
      despite administration of 100% oxygen through a nonrebreather mask. Arterial
      blood gas analysis showed an oxygen saturation of 98% and 97%, respectively.
      Spectroscopic measurement showed methemoglobin concentration of 42% and 35.5%,
      respectively. After red blood cell transfusion and oral ascorbic acid in case 1
      and methylene blue in case 2, the patients' condition improved. Although the
      benzocaine gel is not in use in several medical systems, it should be considered
      as a possible reason for methemoglobinemia.

PMID- 21900834
TI  - Barrett esophagus in long-term survivors of childhood solid tumors.
AB  - We report on 2 cases of long-term survivors of childhood solid tumors, who
      developed Barrett esophagus (BE) after treatment for neuroblastoma and Hodgkin
      lymphoma, respectively. Case 1: A stage 3 neuroblastoma was treated with surgery,
      carboplatin/etoposide chemotherapy, and supradiaphragmatic radiotherapy (30 Gy).
      Twelve years later, based on endoscopic and histologic findings, BE was diagnosed
      on the middle segment. Case 2: A stage IIIB Hodgkin lymphoma received
      mechloretamine, oncovin, procarbazine, prednisone/adriamycin, bleomycin,
      vinblastine, dacarbazine chemotherapy and supra/subdiaphragmatic radiotherapy (25
      Gy). Nineteen years later, BE was diagnosed associated with an esophageal
      stricture. In long-term survivors of childhood tumors who had received chest/neck
      radiotherapy and chemotherapy, the risk of BE may be increased, therefore the
      diagnosis should be considered in the presence of gastroesophageal symptoms.

PMID- 21900835
TI  - Carcinoid tumor with bilateral renal involvement in a child.
AB  - Carcinoid tumors are uncommon in children. Kidneys are rarely involved as they do
      not possess neuro-endocrine cells. Work up of painless hematuria after abdominal
      trauma in a 10-year-old boy revealed primary carcinoid tumors with metastasis to
      both kidneys. We were unable to find any previous reports of renal involvement by
      carcinoid tumor in children.

PMID- 21900836
TI  - A randomized phase II trial of pemetrexed/gemcitabine/bevacizumab or
      pemetrexed/carboplatin/bevacizumab in the first-line treatment of elderly
      patients with advanced non-small cell lung cancer.
AB  - PURPOSE: To assess time to progression (TTP) in elderly patients with previously
      untreated nonsquamous non-small cell lung cancer treated with
      pemetrexed/gemcitabine/bevacizumab or pemetrexed/carboplatin/bevacizumab.
      METHODS: Eligible patients were aged 70 years or older with newly diagnosed stage
      IIIB/IV nonsquamous non-small cell lung cancer; Eastern Cooperative Oncology
      Group performance status 0 to 1; adequate organ function; and no active central
      nervous system metastasis. Patients were randomized 1:1 to cohort A (pemetrexed
      500 mg/m2 IV, gemcitabine 1500 mg/m2 IV, and bevacizumab 10 mg/kg IV; days 1 and
      15 of 28-day cycles) or cohort B (pemetrexed 500 mg/m2 IV, carboplatin area under
      the concentration-time curve =5 IV, and bevacizumab 15 mg/kg IV; day 1 of 21-day
      cycles). After six cycles, stable/responding patients continued bevacizumab until
      disease progression. RESULTS: Between March 2007 and December 2009, 110 patients
      (median age, 76 years; 88% stage IV) were treated for medians of 2.5 cycles
      (cohort A) and 6 cycles (cohort B). Overall response rate was 35% in both
      cohorts, with stable disease rates of 33% (A) and 45% (B). TTP by cohort was 4.7
      and 10.2 months with median OS 7.5 and 14.8 months, respectively. Severe
      toxicities included the following: neutropenia (A, 51% and B, 45%), fatigue (A,
      36% and B, 18%), anemia (A, 22% and B, 7%), infection (A, 25% and B, 7%),
      thrombocytopenia (A, 11% and B, 31%), and thromboembolism (A, 7% and B, 7%).
      Three potential treatment-related deaths occurred in cohort A (sepsis,
      thrombocytopenia, and myocardial infarction) and two in B (sepsis and pulmonary
      hemorrhage). CONCLUSIONS: Treatment with pemetrexed/carboplatin/bevacizumab was
      associated with improved TTP and OS in this elderly population and should be
      further evaluated. Treatment-related toxicities were expected and usually
      manageable, although deaths occurred with both regimens.

PMID- 21900837
TI  - Epidermal growth factor receptor mutation status in circulating free DNA in
      serum: from IPASS, a phase III study of gefitinib or carboplatin/paclitaxel in
      non-small cell lung cancer.
AB  - INTRODUCTION: In IPASS (IRESSA Pan-Asia Study), clinically selected patients with
      pulmonary adenocarcinoma received first-line gefitinib or carboplatin/paclitaxel.
      This preplanned, exploratory analysis was conducted to increase understanding of
      the use of surrogate samples, such as serum, versus tumor biopsy samples for
      determining EGFR mutation status in the Japanese cohort (n = 233). METHODS: EGFR
      mutations were assessed using tumor tissue-derived DNA (n = 91) and circulating
      free (cf) DNA from pretreatment serum samples (n = 194). RESULTS: Fewer patients
      were EGFR mutation positive when assessed using pretreatment cfDNA (23.7%) versus
      tumor tissue-derived DNA (61.5%). cfDNA results identified no false positives but
      a high rate of false negatives (56.9%). There was a significant interaction
      between cfDNA EGFR mutation status and treatment for progression-free survival
      (PFS) (p = 0.045). PFS was significantly longer and objective response rate (ORR)
      higher with gefitinib than carboplatin/paclitaxel in the cfDNA EGFR mutation
      positive subgroup (PFS: hazard ratio [HR], 0.29; 95% confidence interval [CI],
      0.14-0.60; p < 0.001; ORR: odds ratio [OR], 1.71; 95% CI, 0.48-6.09; 75.0% versus
      63.6%; p = 0.40). There was a slight numerical advantage in PFS and ORR for
      gefitinib over carboplatin/paclitaxel in the cfDNA EGFR mutation-negative
      subgroup, likely due to the high rate of false negatives within this subgroup.
      CONCLUSIONS: These results merit further investigation to determine whether
      alternative sources of tumor DNA, such as cfDNA in serum, could be used for
      determining EGFR mutation status in future; currently, where a sample is
      available, analysis of tumor material is recommended.

PMID- 21900838
TI  - Increasing age and carcinoma not otherwise specified: a 20-year population study
      of 40,118 lung cancer patients.
AB  - BACKGROUND AND AIM: New treatment regimens require a differentiation between
      histological subsets of non-small cell lung cancer. We aimed to assess how the
      incidence and prognosis of carcinoma not otherwise specified (NOS) coincide with
      an aging patient population, disease stage, and diagnostic methods used. METHODS:
      Complete national data on 40,118 cases (including 6,597 diagnosed with carcinoma
      NOS) from the Cancer Registry of Norway (1988-2007) are presented. RESULTS: The
      proportion of elderly patients (70 years and older) have increased to over half
      of all patients diagnosed, a trend also evident among carcinoma NOS patients. The
      proportion of carcinomas NOS reported to the cancer registry in this 20-year
      period has increased from 12% in 1988 to 19% in 2007. Crude 5-year relative
      survival in carcinoma NOS was lowest of all non-small cell lung cancer entities
      throughout the 20-year period; however, patients diagnosed with carcinoma NOS in
      the period 2003 to 2007 had about 24% lower risk of dying within 5 years after
      diagnosis compared with patients diagnosed between 1988 and 1992, adjusted for
      covariates. Most lung cancers are diagnosed by biopsy of the primary lesion;
      although the proportion is lower among carcinomas NOS than other histological
      entities. By the last 5-year period studied, carcinoma NOS was the histological
      entity most commonly diagnosed by cytology (38%). CONCLUSION: The proportion of
      carcinomas NOS has increased to 19% of all lung cancer cases. This histological
      entity is associated with older age and poor survival.

PMID- 21900839
TI  - Chest wall sarcomas are accurately diagnosed by image-guided core needle biopsy.
AB  - OBJECTIVE: Sarcomas are rare mesenchymal malignancies. Accurate preoperative
      diagnosis is a prerequisite in considering investigational or institutional
      management algorithms that include neoadjuvant treatment. We reviewed our
      experience using core needle biopsy for chest wall sarcomas. METHODS: A
      retrospective review of our sarcoma databases revealed that 40 core needle
      biopsies and 35 tumor resections were performed in 34 patients, with chest wall
      musculoskeletal tumors, referred to the University of California, Los Angeles
      from 1991 to 2010. Primary, metastatic, or recurrent sarcomas involving the
      sternum, ribs, and soft tissues of the chest wall were evaluated for (1) adequacy
      of tissue from image-guided core needle biopsies and (2) accuracy in determining
      malignancy, histological subtype, and sarcoma grade. RESULTS: Twenty-eight of the
      40 needle biopsy samples (70%) were adequate for histopathological analysis.
      Forty-two percent of nondiagnostic findings occurred due to insufficient tissue,
      whereas the remainder had sufficient tissue, but the pathologist was unable to
      determine specific histology. Excluding the nondiagnostic samples, the accuracy
      in determining malignancy, histological subtype, and grade in sarcomas was 100,
      92, and 87%, respectively. The sensitivity and specificity of determining
      malignancy and high-grade sarcomas were 100, 100, 77, and 100%, respectively.
      There were no complications from the image-guided biopsies. CONCLUSIONS: We
      demonstrated that image-guided core needle biopsy when performed and reviewed by
      experienced radiologists and musculoskeletal pathologists is a safe and accurate
      diagnostic technique for chest wall sarcomas. Core needle biopsy should be
      considered in the multidisciplinary approach to chest wall musculoskeletal
      tumors, especially when induction therapy is considered.

PMID- 21900840
TI  - Everolimus in combination with pemetrexed in patients with advanced non-small
      cell lung cancer previously treated with chemotherapy: a phase I study using a
      novel, adaptive Bayesian dose-escalation model.
AB  - INTRODUCTION: Pemetrexed is an established second-line therapy for non-small cell
      lung cancer (NSCLC). Everolimus has previously been shown to have some clinical
      activity when used as a single agent in NSCLC. The aim of this phase I study was
      to evaluate the safety and feasibility of combining pemetrexed with everolimus in
      patients with NSCLC who had disease progression after one previous treatment.
      METHODS: Patients with stage IIIb/IV NSCLC and one previous chemotherapy regimen
      were enrolled. A Bayesian dose-escalation model was used to determine the
      feasible doses of daily or weekly everolimus combined with pemetrexed (500 mg/m
      q3w). The primary end point was rate of cycle 1 dose-limiting toxicities (DLTs).
      Secondary end points included safety, relative dose intensity of pemetrexed,
      pharmacokinetics, and tumor response. RESULTS: Twenty-four patients received
      daily everolimus (2.5, 5, 7.5, or 10 mg) and 19 received weekly everolimus (30 or
      50 mg) with pemetrexed. Cycle 1 DLTs in the daily regimen included febrile
      neutropenia, neutropenia, rash/pruritus, and thrombocytopenia; in the weekly
      regimen, DLTs included neutropenia and stomatitis. The most frequent grade 3/4
      adverse events were neutropenia, dyspnea, and thrombocytopenia. Three partial
      responses were observed with everolimus 5 mg/d and two with 50 mg/wk.
      Pharmacokinetics did not suggest an influence of everolimus on pemetrexed
      parameters; pemetrexed resulted in a minor decrease in everolimus exposure with
      both daily and weekly regimens. CONCLUSIONS: Everolimus 5 mg/d or 50 mg/wk with
      the standard regimen of pemetrexed are feasible dosages in patients with stage
      IIIb/IV NSCLC.

PMID- 21900841
TI  - Anabolic steroid use and longitudinal, radial, and circumferential cardiac
      motion.
AB  - PURPOSE: The purpose of this study was to investigate the effect of anabolic
      steroid (AS) use on cardiac structure and function and cardiovascular risk
      factors. METHODS: We recruited 47 strength-trained individuals (male = 46, female
      = 1), with 28 self-reporting regular AS use and 19 self-reporting never taking
      AS. Participants underwent assessment of body composition, lipid profiles, blood
      pressure, 12-lead ECG, and a comprehensive echocardiographic examination
      incorporating speckle tracking of longitudinal, radial, and circumferential left
      ventricular (LV) motion. A subgroup of AS users (n = 4) were tested during
      periods of AS use and abstinence. RESULTS: AS users were heavier (96 +/- 15 vs 81
      +/- 9 kg, P < 0.05), had higher LDL (3.68 +/- 0.47 vs 2.41 +/- 0.49 mmol.L-1, P <
      0.05), and had higher resting HR (79 +/- 12 vs 64 +/- 13 beats.min-1), although
      blood pressures did not differ significantly between groups. In AS, LV wall
      thickness and mass were significantly greater (12 +/- 2 vs 11 +/- 1 mm and 280 +/
      60 vs 231 +/- 44 g, respectively, P < 0.05), whereas ejection fractions and peak
      longitudinal strain ([Latin Small Letter Open E]) were significantly lower (58%
      +/- 8% vs 63% +/- 6% and -14.6% +/- 2.3% vs -16.9% +/- 2.2%, P < 0.05). Indices
      of global diastolic function were reduced in AS users (E/A, E'/A'). Some
      diastolic strain rates (ESR and ASR) were altered in AS users. The E/A SR ratio
      was reduced in the longitudinal plane as well as in the circumferential and
      radial plane at the basal level (P < 0.05). Basal LV E/A rotation rate was also
      decreased in AS users (P < 0.05). CONCLUSIONS: AS use is associated with
      alterations in cardiac structure and function that, allied to poor lipid
      profiles, represent an increased cardiovascular risk profile.

PMID- 21900843
TI  - Recreational cycling and cardiorespiratory fitness in English youth.
AB  - PURPOSE: Schoolchildren who cycle to school have higher cardiorespiratory fitness
      (CRF) than those who are driven or use public transport. The purpose of this
      study was to determine whether recreational cycling is similarly associated with
      CRF. METHODS: Participants were 5578 (54% males) English schoolchildren (10.0
      15.9 yr). All reported frequency of recreational cycling events via 7-d recall.
      Responses were categorized as follows: "noncyclists" = 0, "occasional cyclists" =
      1-4, or "regular cyclists" = 5+ (times per week). CRF was assessed using the 20-m
      shuttle run test with performance classified as "fit" or "unfit" based on
      FITNESSGRAM standards. RESULTS: Overall, 26% of males and 46% of females were
      noncyclists. Compared with noncyclists, the 40% of males and 42% of females
      classified as occasional cyclists were more likely to be fit (males: odds ratio
      (OR) = 1.30, 95% confidence interval (CI) = 1.07-1.59; females: OR = 1.41, 95% CI
      = 1.13-1.76). Regular cyclists (34% males and 12% females) had a greater
      likelihood still of being classified as fit (males: OR = 1.58, 95% CI = 1.29
      1.95; females: OR = 1.55, 95% CI = 1.09-2.20). No odds remained significant after
      adjusting for physical activity. Removal of participants who cycled to school had
      little overall effect on the likelihood of being classified as being fit.
      CONCLUSIONS: Previous research has focused only on young people's commuter
      cycling habits, at the expense of the more common activity of recreational
      cycling. Recreational cycling may provide an alternative target for interventions
      to increase physical activity and improve CRF youth. Recreational cycling could
      potentially serve as a way to gain cycling confidence and establish habits that
      act as precursors to commuter cycling.

PMID- 21900842
TI  - Effect of different doses of aerobic exercise training on total bilirubin levels.
AB  - Low serum bilirubin levels have been associated with increased risk for
      cardiovascular disease, and recent data suggest that lower body fat and
      reductions in weight are associated with higher bilirubin levels. However, it is
      unknown if exercise training can increase bilirubin levels and whether a higher
      dose of exercise will further increase bilirubin levels compared with a lower
      dose. PURPOSE: The primary aim of our current report was to examine whether
      exercise dose affects bilirubin levels in obese postmenopausal women from the
      Dose-Response to Exercise in Women trial. In addition, we evaluated whether
      changes in fitness, insulin sensitivity, and waist circumference associated with
      exercise training were associated with change in bilirubin levels. METHODS:
      Participants (n = 419) were randomized to the control group or to 4, 8, and 12
      kcal.kg-1.wk-1 (KKW) of exercise training at an intensity of 50% of aerobic
      capacity. Total bilirubin levels were evaluated at baseline and at follow-up.
      RESULTS: Exercise training significantly increased serum bilirubin levels only in
      the 12-KKW group (0.044 mg.dL-1, P = 0.026) compared with the control group
      (0.004 mg.dL-1). Subgroup analyses showed that there was a significant increase
      in bilirubin levels in participants in the 12-KKW group (0.076 mg.dL-1) who were
      classified as insulin resistant (homeostatic model assessment for insulin
      resistance score > 2.6) compared with insulin-resistant control participants
      (0.018 mg.dL-1, P = 0.028). CONCLUSIONS: Our findings suggest that high doses of
      exercise training are necessary to significantly increase bilirubin levels in
      previously sedentary postmenopausal women and especially those with impaired
      glucose metabolism.

PMID- 21900845
TI  - Strength training with blood flow restriction diminishes myostatin gene
      expression.
AB  - PURPOSE: The aim of the study was to determine whether the similar muscle
      strength and hypertrophy responses observed after either low-intensity resistance
      exercise associated with moderate blood flow restriction or high-intensity
      resistance exercise are associated with similar changes in messenger RNA (mRNA)
      expression of selected genes involved in myostatin (MSTN) signaling. METHODS:
      Twenty-nine physically active male subjects were divided into three groups: low
      intensity (20% one-repetition maximum (1RM)) resistance training (LI) (n = 10),
      low-intensity resistance exercise associated with moderate blood flow restriction
      (LIR) (n = 10), and high-intensity (80% 1RM) resistance exercise (HI) (n = 9).
      All of the groups underwent an 8-wk training program. Maximal dynamic knee
      extension strength (1RM), quadriceps cross-sectional area (CSA), MSTN,
      follistatin-like related genes (follistatin (FLST), follistatin-like 3 (FLST-3)),
      activin IIb, growth and differentiation factor-associated serum protein 1 (GASP
      1), and MAD-related protein (SMAD-7) mRNA gene expression were assessed before
      and after training. RESULTS: Knee extension 1RM significantly increased in all
      groups (LI = 20.7%, LIR = 40.1%, and HI = 36.2%). CSA increased in both the LIR
      and HI groups (6.3% and 6.1%, respectively). MSTN mRNA expression decreased in
      the LIR and HI groups (45% and 41%, respectively). There were no significant
      changes in activin IIb (P > 0.05). FLST and FLST-3 mRNA expression increased in
      all groups from pre- to posttest (P < 0.001). FLST-3 expression was significantly
      greater in the HI when compared with the LIR and LI groups at posttest (P = 0.024
      and P = 0.018, respectively). GASP-1 and SMAD-7 gene expression significantly
      increased in both the LIR and HI groups. CONCLUSIONS: We concluded that LIR was
      able to induce gains in 1RM and quadriceps CSA similar to those observed after
      traditional HI. These responses may be related to the concomitant decrease in
      MSTN and increase in FLST isoforms, GASP-1, and SMAD-7 mRNA gene expression.

PMID- 21900844
TI  - Predicting maximal HR in heart failure patients on beta-blockade therapy.
AB  - PURPOSE: Standards for estimating maximal HR are important when interpreting the
      adequacy of physiologic stress during exercise testing, assessing chronotropic
      response, and prescribing an exercise training regimen. The equation 220 - age is
      used to estimate maximum HR; however, it overestimates measured maximal HR in
      patients taking beta-adrenergic blockade (betaB) therapy. This study developed
      and validated a practical equation to predict maximal HR in patients with heart
      failure (HF) taking betaB therapy. METHODS: Data from symptom-limited exercise
      tests completed on patients with systolic HF participating in the Heart Failure:
      A Controlled Trial Investigating Outcomes of Exercise Training trial and taking a
      betaB agent were used to develop a simplified equation, which was validated using
      bootstrapping. RESULTS: The simplified derived equation was 119 + 0.5 (resting
      HR) - 0.5 (age) - (0, if test was completed using a treadmill; 5, if using a
      stationary bike). The R2 and SEE were 0.28 and 18 beats.min(-1), respectively.
      Validation of this equation yielded a mean R and SEE of 0.28 and 18 beats.min(
      1), respectively. For the equation 220 - age, the R2 was -2.93, and the SEE was
      43 beats.min(-1). CONCLUSIONS: We report a valid and simple population-specific
      equation for estimating peak HR in patients with HF taking betaB therapy. This
      equation should be helpful when evaluating chronotropic response or assessing if
      a maximum effort was provided during exercise testing. We caution, however, that
      the magnitude of the variation (SEE = 18 beats.min(-1)) associated with this
      prediction equation may make it impractical when prescribing exercise intensity.

PMID- 21900846
TI  - Influence of competition on performance and pacing during cycling exercise.
AB  - PURPOSE: The study's purpose was to examine the influence of head-to-head (HH)
      competition on performance, pacing strategy, and bioenergetics during a 2000-m
      cycling task. METHODS: Fourteen participants completed three 2000-m
      familiarization time trials (TTs) on a Velotron cycle ergometer, before
      completing an additional TT and a 2000-m simulated HH competition in a
      counterbalanced order. During the trials, a computer-generated image of the
      participants completing the 2000-m course was projected onto a screen positioned
      in front of the participants. Although participants believed they were competing
      against another individual during the HH competition, they were in fact competing
      against their best familiarization performance (FAM), replayed on the screen by
      the Velotron software. RESULTS: Performance was significantly faster in HH than
      in FAM or TT (184.6 +/- 6.2, 187.7 +/- 8.2, and 188.3 +/- 9.5 s, respectively).
      Pacing profile in HH initially matched the FAM performance but was better
      maintained from 1000 m until the end of exercise. The higher power output during
      the latter part of the test was achieved by a greater anaerobic energy
      contribution, whereas the aerobic energy yield remained unchanged. CONCLUSIONS:
      HH competition encourages participants to increase their performance. This occurs
      primarily via an increased anaerobic energy yield, which seems to be centrally
      mediated, and is consistent with the concept of a physiologic reserve.

PMID- 21900847
TI  - Preschoolers' physical activity, screen time, and compliance with
      recommendations.
AB  - PURPOSE: Little evidence exists about the prevalence of adequate levels of
      physical activity and of appropriate screen-based entertainment in preschool
      children. Previous studies have generally relied on small samples. This study
      investigates how much time preschool children spend being physically active and
      engaged in screen-based entertainment. The study also reports compliance with the
      recently released Australian recommendations for physical activity (>=3 h.d(-1))
      and screen entertainment (<=1 h.d(-1)) and the National Association for Sport and
      Physical Education physical activity guidelines (>=2 h.d(-1)) and American
      Academy of Pediatrics screen-based entertainment recommendations (<=2 h.d(-1)) in
      a large sample of preschool children. METHODS: Participants were 1004 Melbourne
      preschool children (mean age = 4.5 yr, range = 3-5 yr) and their families in the
      Healthy Active Preschool Years study. Physical activity data were collected by
      accelerometry during an 8-d period. Parents reported their child's
      television/video/DVD viewing, computer/Internet, and electronic game use during a
      typical week. A total of 703 (70%) had sufficient accelerometry data, and 935
      children (93%) had useable data on time spent in screen-based entertainment.
      RESULTS: Children spent 16% (approximately 127 min.d(-1)) of their time being
      physically active. Boys and younger children were more active than were girls and
      older children, respectively. Children spent an average of 113 min.d(-1) in
      screen-based entertainment. Virtually no children (<1%) met both the Australian
      recommendations and 32% met both the National Association for Sport and Physical
      Education and American Academy of Pediatrics recommendations. CONCLUSIONS: The
      majority of young children are not participating in adequate amounts of physical
      activity and in excessive amounts of screen-based entertainment. It is likely
      that physical activity may decline and that screen-based entertainment may
      increase with age. Compliance with recommendations may be further reduced.
      Strategies to promote physical activity and reduce screen-based entertainment in
      young children are required.

PMID- 21900848
TI  - Asymmetry of quadriceps muscle oxygenation during elite short-track speed
      skating.
AB  - PURPOSE: It has been suggested that, because of the low sitting position in short
      track speed skating, muscle blood flow is restricted, leading to decreases in
      tissue oxygenation. Therefore, wearable wireless-enabled near-infrared
      spectroscopy (NIRS) technology was used to monitor changes in quadriceps muscle
      blood volume and oxygenation during a 500-m race simulation in short-track speed
      skaters. METHODS: Six elite skaters, all of Olympic standard (age = 23 +/- 1.8
      yr, height = 1.8 +/- 0.1 m, mass = 80.1 +/- 5.7 kg, midthigh skinfold thickness =
      7 +/- 2 mm), were studied. Subjects completed a 500-m race simulation time trial
      (TT). Whole-body oxygen consumption was simultaneously measured with muscle
      oxygenation in right and left vastus lateralis as measured by NIRS. RESULTS: Mean
      time for race completion was 44.8 +/- 0.4 s. VO2 peaked 20 s into the race. In
      contrast, muscle tissue oxygen saturation (TSI%) decreased and plateaued after 8
      s. Linear regression analysis showed that right leg TSI% remained constant
      throughout the rest of the TT (slope value = 0.01), whereas left leg TSI%
      increased steadily (slope value = 0.16), leading to a significant asymmetry (P <
      0.05) in the final lap. Total muscle blood volume decreased equally in both legs
      at the start of the simulation. However, during subsequent laps, there was a
      strong asymmetry during cornering; when skaters traveled solely on the right leg,
      there was a decrease in its muscle blood volume, whereas an increase was seen in
      the left leg. CONCLUSIONS: NIRS was shown to be a viable tool for wireless
      monitoring of muscle oxygenation. The asymmetry in muscle desaturation observed
      on the two legs in short-track speed skating has implications for training and
      performance.

PMID- 21900849
TI  - A phase III, randomized, placebo-controlled, double-blind trial of flaxseed for
      the treatment of hot flashes:  North Central Cancer Treatment Group N08C7.
AB  - OBJECTIVE: Preliminary data suggest that flaxseed, a rich source of dietary
      lignans, may be a potentially effective treatment of hot flashes. A phase III,
      randomized, placebo, controlled trial was conducted to evaluate the efficacy of
      flaxseed in reducing hot flashes. METHODS: Postmenopausal women with or without
      breast cancer were randomly assigned to a flaxseed bar (providing 410 mg of
      lignans) for 6 weeks versus a placebo bar. Participants completed daily,
      prospective, hot flash diaries during the baseline week, and then ate one study
      bar per day for 6 weeks while recording their daily hot flashes. The
      intraparticipant difference in hot flash activity between baseline and the last
      treatment week was the primary endpoint. Adverse effects were evaluated through a
      self-report and the Common Terminology Criteria assessment. RESULTS: A total of
      188 women were enrolled in this trial. The mean hot flash score was reduced 4.9
      in the flaxseed group and 3.5 in the placebo group (P = 0.29). In both groups,
      slightly more than a third of the women received a 50% reduction in their hot
      flash score. Only one adverse effect was significantly different between groups,
      grade 1 pruritus, which was more common in the placebo group (8% vs 1%). Both
      groups reported abdominal distension, flatulence, diarrhea, and nausea. Adherence
      and ability to detect treatment assignment did not differ between groups.
      CONCLUSIONS: The results of this trial do not support the use of 410 mg of
      lignans for the reduction of hot flashes. The bars were fairly well tolerated,
      with both groups reporting gastrointestinal effects, probably due to the fiber
      content.

PMID- 21900851
TI  - The perimenopausal atherosclerosis transition:  relationships between calcified
      and noncalcified coronary, aortic, and carotid atherosclerosis and risk factors
      and hormone levels.
AB  - OBJECTIVE: Women of perimenopause age experience an upward transition of
      cardiovascular risk possibly in association with changing hormonal status. We
      examined the cross-sectional relationships between the atherosclerotic plaque
      within the coronary and carotid arteries and aorta and the menopausal hormone
      levels among asymptomatic perimenopausal women. METHODS: The Assessment of the
      Transition of Hormonal Evaluation with Noninvasive Imaging of Atherosclerosis was
      a prospective substudy of the Prospective Army Coronary Calcium project. We
      screened 126 asymptomatic perimenopausal women (mean age, 50 y) using contrast
      enhanced CT angiography (multidetector CT) and carotid ultrasound. Women had
      coronary calcium data from 5 to 10 years earlier. The measures included
      cardiovascular risk factors, serum hormone levels, 64-slice multidetector CT, and
      carotid ultrasound. RESULTS: The prevalence of any coronary plaque was 35.5%. The
      prevalence of noncalcified plaque was 30.2%, and noncalcified plaque was the only
      manifestation of coronary artery disease in 10.7%. Markers of androgenicity
      (increased free testosterone and reduced sex hormone-binding globulin) were
      associated with an increased extent of calcified and noncalcified coronary artery
      plaque and aortic plaque. However, these relationships were not independent of
      cardiovascular risk factors. Follicle-stimulating hormone was directly associated
      with the number of aortic plaques. The levels of estrogen hormones were unrelated
      to plaque presence or extent. CONCLUSIONS: Coronary, aortic, and carotid arterial
      plaque is prevalent in perimenopausal women without cardiac symptoms. The
      assessment of perimenopausal hormone status was not independently associated with
      subclinical atherosclerosis beyond standard cardiovascular risk factors.

PMID- 21900850
TI  - Negative affect and vasomotor symptoms in the Study of Women's Health Across the
      Nation Daily Hormone Study.
AB  - OBJECTIVE: Vasomotor symptoms (VMS) are common during the menopausal transition.
      Negative affect is consistently associated with self-reported VMS, but the
      interpretation of this relationship is limited by the infrequent measurement and
      retrospective recall of VMS. Using prospective data from daily diaries, we
      examined the daily association between negative affect and reported VMS, as well
      as the temporal associations between negative affect and next-day VMS and between
      VMS and next-day negative affect. METHODS: Data were derived from the third wave
      of the Daily Hormone Study (N = 625). The Daily Hormone Study is a substudy of
      the Study of Women's Health Across the Nation, a multisite community-based
      prospective cohort study of the menopausal transition. Participants reported VMS
      and affect in daily diaries for 12 to 50 days. Multilevel mixed models were used
      to determine the associations between reported VMS and negative affect, adjusted
      by antidepressant use, age, education, menopause status, self-reported health,
      and race/ethnicity, drawn from annual Study of Women's Health Across the Nation
      visits. RESULTS: VMS were reported by 327 women (52.3%). Negative affect was
      positively associated with VMS (odds ratio [OR], 1.76; 95% CI, 1.43-2.17; P <
      0.001) in cross-sectional analyses. Negative affect, adjusted by same-day VMS,
      was not predictive of next-day VMS (OR, 1.11; 95% CI, 0.85-1.35; P = 0.55),
      whereas VMS, adjusted by same-day negative affect, was predictive of negative
      affect for the next day (OR, 1.27; 95% CI, 1.03-1.58; P = 0.01). CONCLUSIONS:
      Negative affect is more likely to be reported on the same day and the day after
      VMS. Potential mechanisms underlying this relationship include negative cognitive
      appraisal, sleep disruption, and unmeasured third factors.

PMID- 21900852
TI  - Structural and functional implications of severe foveal dystopia in epiretinal
      membranes.
AB  - PURPOSE: The purpose of this study was to examine the functional and structural
      correlates of severe foveal dystopia in patients with epiretinal membranes.
      METHODS: For this retrospective study of 29 eyes with epiretinal membrane, we
      identified 7 eyes that had severe foveal dystopia (defined as fovea located >200
      MUm from its expected location) and followed the direction and rate of foveal
      movement pre- and postoperatively. RESULTS: Epiretinal membrane traction caused
      the fovea to move preoperatively at a rate of 275 MUm/month from its anatomical
      location in 2 patients. The final preoperative foveal location was, on average,
      1,217 +/- 683 MUm away from its expected location. Postoperatively, foveal
      movement toward its expected location was largest during the first month after
      surgery (mean = 547 +/- 340 MUm) and slowed down until the final follow-up
      position was achieved (mean = 301 +/- 131 MUm). Overall, the fovea moved a total
      of 848 +/- 445 MUm, allowing the fovea to correct only 32.8 +/- 22.1% of the
      total displacement from its expected location. A univariate regression model
      confirmed a linear relationship between preoperative visual acuity and
      preoperative foveal distance from its expected anatomical location with an R of
      0.759 (P = 0.0107). CONCLUSION: The extent of tractional foveal dystopia
      correlates with decreased visual acuity. Although all patients experienced
      functional and anatomical improvements with surgery, long-standing or severe
      foveal dystopia may be associated with permanent structural changes that limit
      functional outcome. Cases with extreme degrees of foveal dystopia may benefit
      from early intervention to prevent irreversible structural and functional
      changes.

PMID- 21900853
TI  - Indolent nonprogressive multifocal choroidal lesions.
AB  - PURPOSE: We present a case series of four patients with unilateral,
      nonprogressive, yellow or white choroidal lesions of unknown etiology. METHODS:
      Four healthy patients were referred to an academic medical retina practice for
      unusual fundus findings in one eye only. Both eyes of all four patients underwent
      clinical examination and retinal imaging, including fluorescein angiography,
      indocyanine green imaging, and optical coherence tomography. The outcome of this
      series was based on the clinical course of these patients and the features of the
      retinal images. RESULTS: The differential diagnosis based on the clinical
      appearances for these unknown cases includes birdshot chorioretinopathy, lymphoma
      or reactive lymphoid hyperplasia, metastases, orbital and intraocular
      pseudotumor, and bacterial or fungal infection. Extensive workups for these
      clinical entities including HLA-A29, angiotensin-converting enzyme level and
      computed tomography of the chest, liver function testing, magnetic resonance
      imaging of the brain, and orbital ultrasound have remained negative. CONCLUSION:
      Clinical and imaging characteristics for the four patients include absence of
      intraocular inflammation, late staining of lesions on fluorescein angiography,
      and hypofluorescence of lesions on indocyanine green. Lesions were not visible in
      the retina or retinal pigment epithelium using time domain optical coherence
      tomography. However, enhanced depth imaging spectral-domain optical coherence
      tomography imaging available for one patient suggests that these lesions are
      localized to the choroid; further interpretation of this advanced imaging
      technique will likely prove useful in the future. The patients' clinical course
      has remained nonprogressive with no changes over a prolonged period of
      observation. These cases could represent atypical manifestations of known retinal
      disease diagnoses or variations of a new chorioretinal disease process.

PMID- 21900854
TI  - Critical period for foveal fine structure in children with regressed retinopathy
      of prematurity.
AB  - PURPOSE: Midgestation is a critical period in the formation of the foveal
      avascular zone. The authors evaluated the effects of preterm birth on foveal
      structure in children with regressed retinopathy of prematurity. METHODS:
      Children with regressed retinopathy of prematurity with normal-appearing
      posterior poles (n = 26) and full-term control children (n = 56) were
      investigated. Frequency-domain optical coherence tomography 9-mm line scans
      across the fovea were obtained from right eyes. Using a customized segmentation
      program in MATLAB, total retinal thickness and the thickness of individual
      retinal layer regions were measured at the fovea (0 degrees ) and throughout +/-
      8 degrees . RESULTS: Total thickness of the fovea in the retinopathy of
      prematurity group (287.7 +/- 47.6 MUm) was greater than that in the control group
      (230.1 +/- 18.2 MUm). Bilinear fitting was performed to examine the relationship
      between total thickness and gestational age. Before 28 weeks, foveal thickness
      decreased with gestational age (14.3 MUm/week); after 28 weeks, foveal thickness
      decreased only slightly (2.73 MUm/week). Inner retinal layers contributed to the
      difference in thickness between groups more than outer layers. Foveal thickness
      was correlated with gestational age at birth but not with visual acuity or
      refractive error. CONCLUSION: Preterm birth before 28 weeks of gestational age
      was associated with a failure of the inner retinal layers to migrate away from
      the fovea, resulting in increased foveal thickness.

PMID- 21900855
TI  - The expanding role of the anterolateral thigh free flap in head and neck
      reconstruction.
AB  - PURPOSE OF REVIEW: To review the recent literature on the expanding use of the
      anterolateral thigh free flap for head and neck reconstruction. RECENT FINDINGS:
      The versatility of the anterolateral thigh free flap allows it to be raised as a
      subcutaneous, musculocutaneous, fasciocutaneous, or adipofascial flap. In recent
      years, it has been reported to reconstruct defects involving the scalp, skull
      base, pharynx, tracheal stoma, oral cavity, and oropharynx. Various techniques
      have also been described in its harvest and inset, including combination flaps in
      conjunction with other free flaps or bone grafts, chimeric flaps, double-paddled
      skin flaps, and sensate flaps. These reports confer good functional and aesthetic
      outcomes equal to or better than other fasciocutaneous free flaps. SUMMARY: The
      role of the anterolateral thigh free flap in reconstructing head and neck defects
      is ever expanding, with many novel harvesting and reconstructive techniques
      described in recent years. Because of the large surface area of the anterolateral
      thigh, as well as the ability to tailor variable amounts of skin, muscle, fat, or
      fascia associated with this flap, the reconstruction options are numerous. More
      importantly, good functional and aesthetic outcomes are achievable with an
      associated low morbidity of the donor site.

PMID- 21900856
TI  - Modern concepts in computer-assisted craniomaxillofacial reconstruction.
AB  - PURPOSE OF REVIEW: To review the past year's literature regarding current
      computer-assisted reconstruction techniques and their outcomes. RECENT FINDINGS:
      Current computer-assisted craniofacial reconstruction research is focused on data
      acquisition, planning, surgical and assessment phases. The major areas of
      interest among researchers include cosmetic surgery; cleft and craniofacial
      surgery; traumatic reconstruction, head and neck tumor reconstruction; and
      orthognathic surgery and distraction osteogenesis. Recent advances in the fields
      include facial analysis and planning in rhinoplasty, facial surface and bone
      graft volume analysis in cleft surgery, computer-guided tumor ablation and
      osteocutaneous reconstruction in tumor surgery, and preoperative planning and
      surgical assistance in orthognathic and distraction osteogenesis surgery.
      SUMMARY: Research in computer-aided craniofacial surgery is progressing at a
      rapid rate. Rather than just the latest innovation, sound research studies are
      proving computer assistance to be invaluable in producing superior outcomes,
      especially in the fields of head and neck surgery, orthognathic surgery, and
      craniomaxillofacial trauma surgery. Further outcome studies and cost-benefit
      analyses are still needed to show the superiority of these methods to
      contemporary techniques.

PMID- 21900858
TI  - Registered nurses' judgments of the classification and risk level of patient care
      errors.
AB  - As frontline clinicians, nurses play a critical role in mitigating patient harm,
      recovery from health care errors, and overall improvement of patient safety. This
      cross-sectional study asked nurse respondents to make judgments about the
      classification and severity of errors in 4 clinical vignettes. Our results showed
      that agreement about error classification and associated risk among registered
      nurses is less than optimal. Further research is needed to advance our
      understanding of how nurses working in complex patient care situations can
      improve their ability to recognize subtle cues to facilitate early recognition of
      potential errors.

PMID- 21900857
TI  - Do postconcussive symptoms discriminate injury severity in pediatric mild
      traumatic brain injury?
AB  - OBJECTIVES: To assess whether postconcussive symptoms (PCS) can be used to
      discriminate injury severity among children with mild traumatic brain injury
      (TBI). PARTICIPANTS: One hundred eighty-six children with mild TBI, divided into
      high and low injury severity depending on whether the injury was associated with
      a loss of consciousness (LOC), and a comparison group of 99 children with
      orthopedic injuries (OI), all aged 8 to 15 years at the time of injury. MAIN
      MEASURES: Parent-rated frequency and severity of PCS at initial assessment within
      2 weeks postinjury and again at 3 and 12 months postinjury. RESULTS: Ratings of
      PCS obtained at the initial and 3-month assessments differentiated children with
      mild TBI from OI, although only ratings at the initial assessment discriminated
      among all 3 groups. Somatic PCS accounted for most of the discriminatory power.
      CONCLUSIONS: Overall, the accuracy of group classification was relatively modest,
      with a large proportion of misclassifications of children in the mild-TBI groups.
      Although children with mild TBI have more PCS than children with OI, PCS do not
      permit sufficiently accurate discrimination of mild TBI and injury severity to
      warrant diagnostic decisions at this time.

PMID- 21900859
TI  - Reporting of hazards and near-misses in the ambulatory care setting.
AB  - The purpose of this study was to describe the frequency and types of hazard and
      near-miss events in the ambulatory setting. Nursing students (N = 566) submitted
      9272 reports while in their ambulatory care rotation. Of these, 1624 were hazards
      and 985 were near-misses. The most commonly reported hazards and near-misses were
      related to infection (20.0%) and medication (19.1%), respectively. The most
      frequent category of open-ended comments was related to administrative problems.

PMID- 21900860
TI  - Nurse staffing in critical access hospitals: structural factors linked to quality
      care.
AB  - Evidence links the amount of registered nurse care to improved patient outcomes
      in large hospitals, but little is known about registered nurse staffing in small
      critical access hospitals, which comprise 30% of all US hospitals. Our study
      findings show that the unique work environment of critical access hospitals means
      registered nurses are often overextended, reassigned from inpatient care, and/or
      interrupted creating potential safety and quality risks. Further research is
      needed to understand what critical access hospitals consider "safe" levels of
      nurse staffing and what processes are implemented to mitigate these risks.

PMID- 21900861
TI  - Evidence-based design for a safer environment without construction.
AB  - This article explores the implementation of evidence-based design elements in the
      renovation of 1 patient room on a budget of $3500. The functional mock-up was
      evaluated through survey and focus groups by staff, visitors, and physicians to
      identify problematic features. Overall, participants perceived that design
      elements were effective with only minor modification needed before replication.
      Suggestions are provided for ways to implement evidence-based design with limited
      funds.

PMID- 21900862
TI  - Synthesis, spectroscopic properties and antipathogenic activity of new thiourea
      derivatives.
AB  - A number of acylthioureas, 2-((4-methylphenoxy)methyl)-N-(aryl
      carbamothioyl)benzamides (aryl = 3,5-dichlorophenyl, 2,3-dichlorophenyl, 3,4
      dichloro-phenyl, 2,4,5-trichlorophenyl, 3,4,5-trichlorophenyl, 2-bromophenyl, 2,4
      dibromophenyl, 2,5-dibromophenyl, 2-iodophenyl, 3-fluorophenyl, 2,3,4
      trifluorophenyl, 2,4,5-trifluoro-phenyl, 2,4,6-trifluorophenyl) have been
      synthesized, characterized by elemental analysis, IR and NMR spectroscopy and
      tested for their interaction with bacterial cells in free and adherent state. The
      anti-pathogenic activity was correlated with the presence of one iodine, bromide
      or fluorine, and two or three chloride atoms on the N-phenyl substituent of the
      thiourea moiety, being significant especially on Pseudomonas aeruginosa and
      Staphylococcus aureus strains, known for their ability to grow in biofilms. Our
      results demonstrate the potential of these derivatives for further development of
      novel anti-microbial agents with antibiofilm properties.

PMID- 21900863
TI  - Studies on the electrochemical behavior of thiazolidine and its applications
      using a flow-through chronoamperometric sensor based on a gold electrode.
AB  - The electrochemical behaviors of thiazolidine (tetrahydrothiazole) on gold and
      platinum electrodes were investigated in a Britton-Robinson buffer (pH 2.77
      11.61), acetate buffer (pH 4.31), phosphate buffer solutions (pH 2.11 and 6.38)
      and methanol or acetonitrile containing various supporting electrolytes.
      Detection was based on a gold wire electrochemical signal obtained with a
      supporting electrolyte containing 20% methanol-1.0 mM of phosphate buffer (pH
      6.87, potassium dihydrogen phosphate and dipotassium hydrogen phosphate) as the
      mobile phase. Comparison with results obtained with a commercial amperometric
      detector shows good agreement. Using the chronoamperometric sensor with the
      current at a constant potential, and measurements with suitable experimental
      parameters, a linear concentration from 0.05 to 16 mg L-1 was found. The limit of
      quantification (LOQ) of the method for thiazolidine was found to be 1 ng.

PMID- 21900864
TI  - Synthesis of no-carrier-added 4-[18F]fluorophenol from 4-benzyloxyphenyl-(2
      thienyl)iodonium bromide.
AB  - 4-[(18)F]Fluorophenol is a versatile synthon for the synthesis of more complex
      radiopharmaceuticals bearing a 4-[(18)F]fluorophenoxy moiety. In order to prepare
      4-[(18)F]fluorophenol in no-carrier-added (n.c.a.) form only a nucleophilic
      labelling method starting from [(18)F]fluoride is suitable. In this paper a new,
      two step radiosynthesis starting from 4-benzyloxyphenyl-(2-thienyl)iodonium
      bromide and [(18)F]fluoride with subsequent deprotection is described, yielding
      n.c.a. [(18)F]fluorophenol in 34 to 36% radiochemical yield.

PMID- 21900865
TI  - Synthesis and structural characterization of 1-[2-(5-nitro-1H-indol-2
      yl)phenyl]methylpyridinium chloride.
AB  - In the course of studies on hybrid antibacterials incorporating 2-aryl-5-nitro-1H
      indole moieties as potential bacterial NorA efflux pump inhibitors, the compound
      1-[2-(5-nitro-1H-indol-2-yl)phenyl]methylpyridinium chloride (2) was synthesized
      and structurally characterized. This pyridinium chloride salt crystallized in the
      monoclinic space group P2(1)/c with the following unit cell dimensions: a
      10.274(3) A, b 13.101(4) A, c 13.439(4) A, b 107.702(7) degrees , V 1723.2(9) A3,
      Z (f.u.) = 4; R1 = 0.048, and wR2 = 0.13. Of interest in the single crystal X-ray
      structure is the (intramolecular) disposition of the pyridinium plane over the
      indole heterocyclic residue [interplanar dihedral angle 17.91(4) degrees ].

PMID- 21900866
TI  - A novel anti-inflammatory role for ginkgolide B in asthma via inhibition of the
      ERK/MAPK signaling pathway.
AB  - Ginkgolide B is an anti-inflammatory extract of Ginkgo biloba and has been used
      therapeutically. It is a known inhibitor of platelet activating factor (PAF),
      which is important in the pathogenesis of asthma. Here, a non-infectious mouse
      model of asthma is used to evaluate the anti-inflammatory capacity of ginkgolide
      B (GKB) and characterize the interaction of GKB with the mitogen activated
      protein kinase (MAPK) pathway. BALB/c mice that were sensitized and challenged to
      ovalbumin (OVA) were treated with GKB (40 mg/kg) one hour before they were
      challenged with OVA. Our study demonstrated that GKB may effectively inhibit the
      increase of T-helper 2 cytokines, such as interleukin (IL)-5 and IL-13 in
      bronchoalveolar lavage fluid (BALF). Furthermore, the eosinophil count in BALF
      significantly decreased after treatment of GKB when compared with the OVA
      challenged group. Histological studies demonstrated that GKB substantially
      inhibited OVA-induced eosinophilia in lung tissue and mucus hyper-secretion by
      goblet cells in the airway. These results suggest that ginkgolide B may be useful
      for the treatment of asthma and its efficacy is related to suppression of
      extracellular regulating kinase/MAPK pathway.

PMID- 21900867
TI  - Synthesis of quinolin-2-one alkaloid derivatives and their inhibitory activities
      against HIV-1 reverse transcriptase.
AB  - Based on an established common pharmacophore of HIV-1 non-nucleoside reverse
      transcriptase inhibitors (NNTTIs), a series of quinolin-2-one derivatives were
      synthesized and assayed for their in vitro activities against HIV-1 reverse
      transcriptase (RT) for the first time. Some of the tested compounds were active
      against HIV-1 RT. Compounds 4a2 and 4d2 showed inhibitory activities with IC(50)
      values of 0.21 and 0.15 mM, respectively, with a mode of interaction with RT
      residues of the allosteric pocket similar to that of efavirenz.

PMID- 21900868
TI  - Synthesis of some oxadiazole derivatives as new anticandidal agents.
AB  - In this study, 5-[(pyrimidin-2-ylthio)methyl]-1,3,4-oxadiazole-2(3H)-thione (3)
      was synthesized via the ring closure reaction of 2-(pyrimidin-2
      ylthio)acetohydrazide (2) with carbon disulphide. New oxadiazole derivatives 4a-f
      were obtained by the nucleophilic substitution reaction of compound 3 with
      various phenacyl bromides. The chemical structures of the compounds were
      elucidated by IR, 1H-NMR, 13C-NMR and FAB+-MS spectral data and elemental
      analyses. The newly synthesized derivatives 4a-f were tested in vitro by using a
      microbroth dilution method against C. albicans (clinical isolate, Osmangazi
      University, Faculty of Medicine, Eskisehir, Turkey), C. albicans (ATCC 90028), C.
      glabrata (clinical isolate, Osmangazi University, Faculty of Medicine, Eskisehir,
      Turkey), C. tropicalis (NRRL Y-12968), C. krusei (NRRL Y-7179), C. parapsilosis
      (NRRL Y- 12696), C. albicans (NRRL Y-12983), C. glabrata (clinical isolate,
      Anadolu University, Faculty of Science, Department of Biology, Eskisehir,
      Turkey). Among these compounds, compound 4a was found to be the most potent
      derivative (MIC = 0.007-0.06 versus ketoconazole: 0.001-0.007 mg/mL) against
      Candida species, except C. tropicalis and C. krusei when compared with the
      standard antifungal ketoconazole.

PMID- 21900869
TI  - Antioxidant and antiacetylcholinesterase activities of some commercial essential
      oils and their major compounds.
AB  - The commercial essential oils of Citrus aurantium L., Cupressus sempervirens L.,
      Eucalyptus globulus Labill., Foeniculum vulgare Mill. and Thymus vulgaris L.,
      isolated by steam distillation by a company of Morocco were evaluated in terms of
      in vitro antioxidant activity through several methods. In vitro
      acetylcholinesterase inhibitory activity was also determined. Citrus limon (L.)
      Burm. f. oil was also studied, but it was obtained by peel expression. The best
      antioxidant was T. vulgaris oil, independent of the method used, mainly due to
      the presence of the phenolic monoterpenes thymol and carvacrol, which when
      studied as single compounds also presented the best activities. Concerning the
      acetylcholinesterase inhibition activity, E. globulus was the most effective.
      Nevertheless its main components 1,8-cineole and limonene were not the most
      active, a feature that corresponded to d-3-carene.

PMID- 21900870
TI  - Synthesis and transformations of di-endo-3-aminobicyclo-[2.2.2]oct-5-ene-2
      carboxylic acid derivatives.
AB  - all-endo-3-amino-5-hydroxybicyclo[2.2.2]octane-2-carboxylic acid (13) and all
      endo-5-amino-6-(hydroxymethyl)bicyclo[2.2.2]octan-2-ol (10) were prepared via
      dihydro-1,3-oxazine or g-lactone intermediates by the stereoselective
      functionalization of an N-protected derivative of endo-3-aminobicyclo[2.2.2]oct-5
      ene-2-carboxylic acid (2). Ring closure of b-amino ester 4 resulted in tricyclic
      pyrimidinones 15 and 16. The structures, stereochemistry and relative
      configurations of the synthesized compounds were determined by IR and NMR.

PMID- 21900871
TI  - Chemical suicides in automobiles--six states, 2006-2010.
AB  - During a 3-month period in 2008 in Japan, 208 persons committed suicide by mixing
      household chemicals and, while in a confined space, breathing in the resultant
      poisonous gas. The large number of similar suicides is believed to have resulted
      from the posting of directions for generating poisonous gas on the Internet. In
      addition to claiming the suicide victim, lethal gas generated by intentionally
      mixing household chemicals can leak from confined spaces, triggering evacuations,
      and exposing bystanders and first responders to injury. Chemical suicides similar
      to those in Japan in 2008 have been reported increasingly in the United States,
      with the majority occurring inside automobiles. To characterize such incidents in
      the United States, the Agency for Toxic Substances and Disease Registry (ATSDR)
      analyzed reports of chemical suicides and attempted suicides that occurred in
      automobiles, using 2006--2009 data from states participating in the Hazardous
      Substances Emergency Events Surveillance (HSEES) system and 2010 data from states
      participating in the new National Toxic Substance Incidents Program (NTSIP). This
      report summarizes the results of that analysis, which found that, during 2006-
      2010, a total of 10 chemical suicide incidents were reported from six states,
      resulting in the deaths of nine suicide victims and injuries to four law
      enforcement officers. When responding to suspected chemical suicide incidents,
      emergency responders must take precautions to ensure both their safety and the
      safety of any bystanders in the immediate vicinity.

PMID- 21900872
TI  - Maternal and infant outcomes among severely ill pregnant and postpartum women
      with 2009 pandemic influenza A (H1N1)--United States, April 2009-August 2010.
AB  - Pregnant women with influenza are at increased risk for hospitalization and
      death. Since 2004, the Advisory Committee on Immunization Practices (ACIP) has
      recommended inactivated influenza vaccine for all women who are pregnant during
      influenza season, regardless of trimester. Nonetheless, after the 2004
      recommendation, estimated annual influenza vaccination coverage among pregnant
      women was approximately 15%, before increasing to nearly 50% during the 2009
      influenza A (H1N1) pandemic. Since April 2009, CDC has collaborated with state
      and local health departments to conduct enhanced surveillance for severe
      influenza among pregnant and postpartum women. To assess maternal and infant
      outcomes among severely ill pregnant and postpartum women with 2009 H1N1 during
      the 2009 H1N1 pandemic, CDC analyzed data for the period April 15, 2009 to August
      10, 2010. This report summarizes the results of that analysis, which found that,
      among 347 severely ill pregnant women, 75 died from 2009 H1N1, and 272 were
      admitted to an intensive-care unit (ICU) and survived. Women who survived
      received antiviral treatment sooner after symptom onset than women who died.
      Pregnant women with severe influenza who delivered during their influenza
      hospitalization were more likely to deliver preterm and low birth weight infants
      than those in the general U.S. population; infants born after their mother's
      influenza hospitalization discharge were more likely to be small for gestational
      age. These data document the severe effects of 2009 H1N1 on pregnant women and
      their infants, emphasize the importance of vaccinating pregnant women against
      influenza, and demonstrate the value of prompt administration of antivirals to
      pregnant women with suspected or confirmed influenza.

PMID- 21900873
TI  - Surveillance for foodborne disease outbreaks--United States, 2008.
AB  - Foodborne agents cause an estimated 48 million illnesses annually in the United
      States, including 9.4 million illnesses from known pathogens. CDC collects data
      on foodborne disease outbreaks submitted from all states and territories through
      the Foodborne Disease Outbreak Surveillance System. During 2008, the most recent
      year for which data are finalized, 1,034 foodborne disease outbreaks were
      reported, which resulted in 23,152 cases of illness, 1,276 hospitalizations, and
      22 deaths. Among the 479 outbreaks with a laboratory-confirmed single etiologic
      agent reported, norovirus was the most common, accounting for 49% of outbreaks
      and 46% of illnesses. Salmonella was the second most common, accounting for 23%
      of outbreaks and 31% of illnesses. Among the 218 outbreaks attributed to a food
      vehicle with ingredients from only one of 17 defined food commodities, the top
      commodities to which outbreaks were attributed were poultry (15%), beef (14%),
      and finfish (14%), whereas the top commodities to which outbreak-related
      illnesses were attributed were fruits and nuts (24%), vine-stalk vegetables
      (23%), and beef (13%). Outbreak surveillance provides insights into the agents
      that cause foodborne illness, types of implicated foods, and settings where
      transmission occurs. Public health, regulatory, and food industry professionals
      can use this information to target prevention efforts against pathogens and foods
      that cause the most foodborne disease outbreaks.

PMID- 21900874
TI  - Respiratory syncytial virus--United States, July 2007-June 2011.
AB  - Each year in the United States, an estimated 75,000-125,000 hospitalizations
      related to respiratory syncytial virus (RSV)occur among children aged <1 year,
      and RSV infection results in approximately 1.5 million outpatient visits among
      children aged <5 years. In the United States, RSV season begins in the fall,
      peaks in winter, and ends in the late winter and early spring. However, the exact
      timing and duration vary from year to year and by geographic region. To describe
      trends in RSV seasonality, data from the National Respiratory and Enteric Virus
      Surveillance System (NREVSS) were used to determine the onset, offset, and peak
      of the July 2010--June 2011 RSV season, and for an aggregate analysis of the four
      most recent RSV seasons (July 2007--June 2011). During 2010--11, excluding
      Florida, season onset occurred from mid-November to early January, and offset
      occurred from mid-March to late April across all 10 U.S. Department of Health and
      Human Services (HHS) regions. Florida is reported separately because it has an
      earlier onset and longer duration than the rest of the country. During the four
      seasons from 2007 through 2011, onset among the HHS regions excluding Florida
      ranged from mid-October to early January, and offset ranged from early February
      to early May. Information on national and regional patterns can be used by
      clinicians and public health officials to guide diagnostic testing during
      respiratory disease outbreaks and determine when to provide RSV immunoprophylaxis
      for children at high risk for serious complications.

PMID- 21900875
TI  - Vital signs: current cigarette smoking among adults aged >=18 years--United
      States, 2005-2010.
AB  - BACKGROUND: Tobacco use remains the leading cause of preventable morbidity and
      mortality in the United States. METHODS: The 2005--2010 National Health Interview
      Surveys and the 2010 Behavioral Risk Factor Surveillance System survey were used
      to estimate national and state adult smoking prevalence, respectively. Current
      cigarette smokers were defined as adults aged >=18 years who reported having
      smoked >=100 cigarettes during their lifetime and who now smoke every day or some
      days. RESULTS: In 2010, 19.3% of U.S. adults were current cigarette smokers.
      Higher smoking prevalence was observed in the Midwest (21.8%) and South (21.0%).
      From 2005 to 2010, the proportion of smokers declined from 20.9% to 19.3% (p<0.05
      for trend), representing approximately 3 million fewer smokers in 2010 than would
      have existed had prevalence not declined since 2005. The proportion of daily
      smokers who smoked one to nine cigarettes per day (CPD) increased from 16.4% to
      21.8% during 2005-2010 (p<0.05 for trend), whereas the proportion who smoked >=30
      CPD decreased from 12.7% to 8.3% (p<0.05 for trend). CONCLUSIONS: During 2005
      2010, an overall decrease was observed in the prevalence of cigarette smoking
      among adults; however, the amount and direction of change has not been consistent
      year-to-year. IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Enhanced efforts are
      needed to accelerate the decline in cigarette smoking among adults. Population
      based prevention strategies, such as tobacco taxes, media campaigns, and smoke
      free policies, in concert with clinical cessation interventions, can help
      decrease cigarette smoking and reduce the health burden and economic impact of
      tobacco-related diseases in the United States.

PMID- 21900876
TI  - Swine-origin influenza A (H3N2) virus infection in two children--Indiana and
      Pennsylvania, July-August 2011.
AB  - Influenza A viruses are endemic in many animal species, including humans, swine,
      and wild birds, and sporadic cases of transmission of influenza A viruses between
      humans and animals do occur, including human infections with avian-origin
      influenza A viruses (i.e., H5N1 and H7N7) and swine-origin influenza A viruses
      (i.e., H1N1, H1N2, and H3N2). Genetic analysis can distinguish animal origin
      influenza viruses from the seasonal human influenza viruses that circulate widely
      and cause annual epidemics. This report describes two cases of febrile
      respiratory illness caused by swine-origin influenza A (H3N2) viruses identified
      on August 19 and August 26, 2011, and the current investigations. No
      epidemiologic link between the two cases has been identified, and although
      investigations are ongoing, no additional confirmed human infections with this
      virus have been detected. These viruses are similar to eight other swine-origin
      influenza A (H3N2) viruses identified from previous human infections over the
      past 2 years, but are unique in that one of the eight gene segments (matrix [M]
      gene) is from the 2009 influenza A (H1N1) virus. The acquisition of the M gene in
      these two swine-origin influenza A (H3N2) viruses indicates that they are
      "reassortants" because they contain genes of the swine-origin influenza A (H3N2)
      virus circulating in North American pigs since 1998 and the 2009 influenza A
      (H1N1) virus that might have been transmitted to pigs from humans during the 2009
      H1N1 pandemic. However, reassortments of the 2009 influenza A (H1N1) virus with
      other swine influenza A viruses have been reported previously in swine.
      Clinicians who suspect influenza virus infection in humans with recent exposure
      to swine should obtain a nasopharyngeal swab from the patient for timely
      diagnosis at a state public health laboratory and consider empiric neuraminidase
      inhibitor antiviral treatment to quickly limit potential human transmission.

PMID- 21900877
TI  - Identification of two novel CAKUT-causing genes by massively parallel exon
      resequencing of candidate genes in patients with unilateral renal agenesis.
AB  - Congenital abnormalities of the kidney and urinary tract (CAKUT) are the most
      frequent cause of chronic kidney disease in children, accounting for about half
      of all cases. Although many forms of CAKUT are likely caused by single-gene
      defects, mutations in only a few genes have been identified. In order to detect
      new contributing genes we pooled DNA from 20 individuals to amplify all 313 exons
      of 30 CAKUT candidate genes by PCR analysis and massively parallel exon
      resequencing. Mutation carriers were identified by Sanger sequencing. We repeated
      the analysis with 20 new patients to give a total of 29 with unilateral renal
      agenesis and 11 with other CAKUT phenotypes. Five heterozygous missense mutations
      were detected in 2 candidate genes (4 mutations in FRAS1 and 1 in FREM2) not
      previously implicated in non-syndromic CAKUT in humans. All of these mutations
      were absent from 96 healthy control individuals and had a PolyPhen score over
      1.4, predicting possible damaging effects of the mutation on protein function.
      Recessive truncating mutations in FRAS1 and FREM2 were known to cause Fraser
      syndrome in humans and mice; however, a phenotype in heterozygous carriers has
      not been described. Thus, heterozygous missense mutations in FRAS1 and FREM2
      cause non-syndromic CAKUT in humans.

PMID- 21900878
TI  - Medullary amyloidosis associated with apolipoprotein A-IV deposition.
AB  - Amyloidosis is caused by extracellular deposition of proteins in an insoluble
      manner within tissues. In hereditary forms of amyloidosis, transthyretin,
      fibrinogen A-alpha, lysozyme, gelsolin, apolipoprotein A-I, and A-II accumulate
      in the tissue plaques. Here we describe a 52-year-old man with no family history
      of renal disease who presented with increased urinary frequency, gradual loss of
      renal function but no significant proteinuria. Renal biopsy found large amounts
      of amyloid restricted to the medulla with no involvement of glomeruli or vessels.
      Immunohistochemical analysis for transthyretin or serum amyloid A and tests for
      an underlying monoclonal gammopathy were negative. Although initially suspected
      to be amyloid light chain amyloidosis, laser microdissection and mass
      spectrometry showed that the amyloid was composed of large amounts of
      apolipoprotein A-IV. This was based on mass spectrometry studies that showed 100,
      96, and 73 spectra in three microdissected samples that matched to apolipoprotein
      A-IV with 100% probability. DNA analyses detected three sequence variants
      representing common polymorphisms of the apolipoprotein A-IV gene. Thus, in this
      case, apolipoprotein A-IV deposition and renal involvement appear to be
      restricted to the medulla. A high degree of suspicion is required for the
      diagnosis of apolipoprotein A-IV amyloidosis as it may be missed if a renal
      biopsy consists only of cortex.

PMID- 21900879
TI  - Proteinuria and hypertension with tyrosine kinase inhibitors.
AB  - Tyrosine kinases are important for the development of pathological angiogenesis,
      a critical factor for survival and proliferation of tumor cells. Inhibition of
      tyrosine kinases either through targeted binding of its ligands or inhibition of
      its receptor has led to significant hindrance in angiogenesis and has improved
      survival for several cancers. Several of these antibodies or small molecules have
      been approved for treatment of recurrent and resistant cancers over the last
      decade. Although generally well tolerated, tyrosine kinase inhibitors have been
      linked with development of hypertension and proteinuria. We review the literature
      for incidence and severity of hypertension and proteinuria among several tyrosine
      kinase inhibitors, their pathophysiologic mechanisms, and provide a guide for
      screening and management.

PMID- 21900880
TI  - Cysteamine therapy delays the progression of nephropathic cystinosis in late
      adolescents and adults.
AB  - Nephropathic cystinosis is a multisystem autosomal recessive disease caused by
      cystine accumulation, which is usually treated by oral cysteamine. In order to
      determine long-term effects of this therapy, we enrolled 86 adult patients (mean
      age 26.7 years) diagnosed with nephropathic cystinosis, 75 of whom received
      cysteamine. Therapy was initiated at a mean age of 9.9 years with a mean duration
      of 17.4 years. By last follow-up, 78 patients had end-stage renal disease (mean
      age 11.1 years), 62 had hypothyroidism (mean age 13.4), 48 developed diabetes
      (mean age 17.1 years), and 32 had neuromuscular disorders (mean age 23.3 years).
      Initiating cysteamine therapy before 5 years of age significantly decreased the
      incidence and delayed the onset of end-stage renal disease, and significantly
      delayed the onset of hypothyroidism, diabetes, and neuromuscular disorders. The
      development of diabetes and hypothyroidism was still significantly delayed,
      however, in patients in whom therapy was initiated after 5 years of age, compared
      with untreated patients. The life expectancy was significantly improved in
      cysteamine-treated versus untreated patients. Thus, cysteamine decreases and
      delays the onset of complications and improves life expectancy in cystinosis.
      Hence, cysteamine therapy should be introduced as early as possible during
      childhood and maintained lifelong.

PMID- 21900881
TI  - Inhibition of histone deacetylases targets the transcription regulator Id2 to
      attenuate cystic epithelial cell proliferation.
AB  - The pan-histone deacetylase (HDAC) inhibitor, trichostatin A, was found to reduce
      cyst progression and slow the decline of kidney function in Pkd2 knockout mice,
      model of autosomal dominant polycystic kidney disease (ADPKD). Here we determine
      whether HDAC inhibition acts by regulating cell proliferation to prevent cyst
      formation, or by other mechanisms. The loss of Pkd1 caused an upregulation of the
      inhibitor of differentiation 2 (Id2), a transcription regulator, triggering an
      Id2-mediated downregulation of p21 in mutant mouse embryonic kidney cells in
      vitro. Using mouse embryonic kidney cells, mutant for Pkd1, we found that
      trichostatin A decreased Id2, which resulted in upregulation of p21. Further,
      phosphorylated retinoblastoma (Rb), usually regulated by Cdk2/Cdk4 activity, was
      also reduced in these cells. Since these latter enzymes are under the control of
      p21, these studies suggest that the proliferation of cyst epithelial cells that
      is reduced by trichostatin A might result from p21 upregulation, or alternatively
      through the Rb-E2F pathway. Additional studies showed that Id2 directly bound to
      Rb, releasing the transcription activator E2F from transcriptionally inactive Rb
      E2F complexes. HDAC inhibition was able to reverse this process by downregulation
      of Id2. Furthermore, treatment of pregnant Pkd1 mice with trichostatin A
      prevented cyst formation in the developing embryonic kidneys, showing that this
      inhibition is effective in vivo during early cyst formation. Thus, HDAC
      inhibition targets Id2-mediated pathways to downregulate cystic epithelial cell
      proliferation and hence cystogenesis.

PMID- 21900882
TI  - 7,8-dihydroxyflavone, a small-molecule TrkB agonist, reverses memory deficits and
      BACE1 elevation in a mouse model of Alzheimer's disease.
AB  - Increasing evidence suggests that reductions in brain-derived neurotrophic factor
      (BDNF) and its receptor tyrosine receptor kinase B (TrkB) may have a role in the
      pathogenesis of Alzheimer's disease (AD). However, the efficacy and safety
      profile of BDNF therapy (eg, gene delivery) remains to be established toward
      clinical trials. Here, we evaluated the effects of 7,8-dihydroxyflavone (7,8
      DHF), a recently identified small-molecule TrkB agonist that can pass the blood
      brain barrier, in the 5XFAD transgenic mouse model of AD. 5XFAD mice at 12-15
      months of age and non-transgenic littermate controls received systemic
      administration of 7,8-DHF (5 mg/kg, i.p.) once daily for 10 consecutive days. We
      found that 7,8-DHF rescued memory deficits of 5XFAD mice in the spontaneous
      alternation Y-maze task. 5XFAD mice showed impairments in the hippocampal BDNF
      TrkB pathway, as evidenced by significant reductions in BDNF, TrkB receptors, and
      phosphorylated TrkB. 7,8-DHF restored deficient TrkB signaling in 5XFAD mice
      without affecting endogenous BDNF levels. Meanwhile, 5XFAD mice exhibited
      elevations in the beta-secretase enzyme (BACE1) that initiates amyloid-beta
      (Abeta) generation, as observed in sporadic AD. Interestingly, 7,8-DHF blocked
      BACE1 elevations and lowered levels of the beta-secretase-cleaved C-terminal
      fragment of amyloid precursor protein (C99), Abeta40, and Abeta42 in 5XFAD mouse
      brains. Furthermore, BACE1 expression was decreased by 7,8-DHF in wild-type mice,
      suggesting that BDNF-TrkB signaling is also important for downregulating baseline
      levels of BACE1. Together, our findings indicate that TrkB activation with
      systemic 7,8-DHF can ameliorate AD-associated memory deficits, which may be, at
      least in part, attributable to reductions in BACE1 expression and beta
      amyloidogenesis.

PMID- 21900883
TI  - The Alcohol Clinical Trials Initiative (ACTIVE): purpose and goals for assessing
      important and salient issues for medications development in alcohol use
      disorders.
AB  - Although progress has been made in the treatment of alcohol use disorders, more
      effective treatments are needed. In the last 15 years, several medications have
      been approved for use in alcohol dependence but have only limited effectiveness
      and clinical acceptance. While academics have developed some 'standards' for the
      performance of clinical trials for alcohol dependence, they vary considerably, in
      the type of populations to be studied, the length of trials, salient outcome
      measures, and data analyses to be used (especially in the treatment of missing
      data). This variability impedes the commercial development of medications to
      treat alcohol dependence. Using a model similar to that used to develop an expert
      consensus for medications to improve cognitive aspects of schizophrenia (MATRICS)
      and in the treatment of pain (IMMPACT), a workgroup has been formed under the
      auspices of ACNP, known as the ACTIVE (Alcohol Clinical Trials Initiative) group,
      to evaluate data from completed clinical trials to develop a consensus on key
      issues in the conduct of clinical trials in alcohol dependence. ACTIVE consists
      of academic experts, industry representatives, and staff from the Food and Drug
      Administration, the National Institute on Alcohol Abuse and Alcoholism, and the
      National Institute on Drug Abuse. This paper describes the rationale behind the
      effort, its history and organization, and initial key questions that have been
      identified as the primary focus of the workgroup. Future papers will focus on
      knowledge gained from the re-analysis of completed trials and provide consensus
      opinions regarding the performance of clinical trials that might be undertaken in
      the future.

PMID- 21900885
TI  - GABA(A) receptor blockade enhances memory consolidation by increasing hippocampal
      BDNF levels.
AB  - Memory consolidation is the process by which acquired information is converted to
      something concrete to be retrieved later. Here we examined a potential role for
      brain-derived neurotrophic factor (BDNF) in mediating the enhanced memory
      consolidation induced by the GABA(A) receptor antagonist, bicuculline methiodide.
      With the administration of an acquisition trial in naive mice using a passive
      avoidance task, mature BDNF (mBDNF) levels were temporally changed in the
      hippocampal CA1 region, and the lowest levels were observed 9 h after the
      acquisition trial. In the passive avoidance task, bicuculline methiodide
      administration within 1 h of training but not after 3 h significantly increased
      latency time in the retention trial 24 h after the acquisition trial.
      Concomitantly, 1 h post-training administration of bicuculline methiodide, which
      enhanced memory consolidation, significantly increased mBDNF levels 9 h after
      training compared to those of the vehicle-treated control group. In addition,
      exogenous human recombinant BDNF (hrBDNF) administration 9 h after training into
      the hippocampal CA1 region facilitated memory consolidation confirming that the
      increase in mBDNF at around 9 h after training plays a key role in the
      enhancement of memory consolidation. Moreover, the increases in latency time and
      immediate early gene expressions by bicuculline methiodide or hrBDNF were
      significantly blocked by anisomycin, a protein synthesis inhibitor, K252a, a
      tyrosine receptor kinase (Trk) inhibitor, or anti-TrkB IgG. These findings
      suggest that the increase in the level of mBDNF and its function during a
      restricted time window after training are required for the enhancement of memory
      consolidation by GABA(A) receptor blockade.

PMID- 21900887
TI  - Prolonged use of aspirin alters human and rat intestinal cells and thereby limits
      the absorption of clopidogrel.
AB  - Clopidogrel therapy to prevent atherothrombosis faces the challenge of reduced
      responsiveness. The absorption of clopidogrel is regulated by multidrug
      resistance protein 1 (MDR1) in the intestinal epithelium. Given that aspirin
      induces MDR1 in cancer cells and peripheral blood cells, it may induce MDR1 in
      intestinal epithelial cells as well, thereby affecting the absorption of
      clopidogrel. In this study, aspirin treatment induced the expression of MDR1 in
      human epithelial colorectal (Caco-2) cells in vitro and in rat intestine in vivo,
      as evidenced by dose-dependent increases in gene, protein, and efflux function.
      Along with the upregulation of MDR1 proteins by aspirin, clopidogrel absorption
      was significantly decreased in the aspirin-treated Caco-2 cells and in rat
      intestine. Our data provide evidence that prolonged use of aspirin may reduce the
      intestinal absorption of clopidogrel. Further human studies would be necessary to
      clarify whether these data have any relevance to prevention of stroke or
      myocardial infarction.

PMID- 21900888
TI  - The stuttering progress of cell therapy for heart disease.
AB  - Stem cell therapy has emerged as a potential therapeutic strategy for myocardial
      infarction (MI). Multiple cell types used to regenerate the injured heart have
      been tested in clinical trials. The results of studies of skeletal myoblasts
      (SKMs) have been resoundingly negative, and the bone marrow-derived-cell
      experience leaves much to be desired. A number of lessons arise from the large
      scale bone marrow-derived-cell trials: (i) efficacy has been inconsistent and,
      overall, modest; however, unexpectedly meaningful benefits on clinical end points
      have been reported; (ii) cardiac engraftment of cells is disappointingly low, and
      delivery methods need to be optimized and combined with strategies to boost
      retention; (iii) the cardiomyogenic potential of bone marrow cells is low;
      however, functional benefit can be achieved through indirect pathways; and (iv)
      autologous cell therapy has severe limitations; highly standardized allogeneic
      cell products are attractive. Given the spotty trajectory of cell therapy to
      date, a more systematic approach to product development and preclinical
      optimization will facilitate more effective clinical translation.

PMID- 21900886
TI  - Pharmacogenetics of naltrexone in asian americans: a randomized placebo
      controlled laboratory study.
AB  - Recent clinical and laboratory studies have shown that the effects of naltrexone
      for alcoholism may be moderated by the Asn40Asp single-nucleotide polymorphism
      (SNP) of the MU-opioid receptor gene (OPRM1). Allele frequencies for this
      polymorphism, however, have been shown to vary substantially as a function of
      ethnic background, such that individuals of Asian descent are more likely to
      carry the minor (Asp40) allele. The objective of this study is to test the
      naltrexone pharmacogenetic effects of the Asn40Asp SNP in a sample of Asian
      Americans. This study consists of a double-blinded, randomized, placebo
      controlled laboratory trial of naltrexone. Participants (n=35, 10 females; 13
      Asn40Asn and 22 Asp40 carriers) were non-treatment-seeking heavy drinkers
      recruited from the community. After taking naltrexone or placebo, participants
      completed an intravenous alcohol administration session. The primary outcome
      measures were subjective intoxication and alcohol craving. Results suggested that
      Asp40 carriers experienced greater alcohol-induced sedation, subjective
      intoxication, and lower alcohol craving on naltrexone, as compared to placebo,
      and to Asn40 homozygotes. There results were maintained when controlling for
      ALDH2 (rs671) and ADH1B (rs1229984) markers and when examining the three levels
      of OPRM1 genotype, thereby supporting an OPRM1 gene dose response. These findings
      provide a much-needed extension of previous studies of naltrexone
      pharmacogenetics to individuals of Asian descent, an ethnic group more likely to
      express the minor allele putatively associated with improved biobehavioral and
      clinical response to this medication. These findings help further delineate the
      biobehavioral mechanisms of naltrexone and its pharmacogenetics.

PMID- 21900890
TI  - Increasing tamoxifen dose in breast cancer patients based on CYP2D6 genotypes and
      endoxifen levels: effect on active metabolite isomers and the antiestrogenic
      activity score.
AB  - Tamoxifen (Tam), the major drug for estrogen receptor (ER)-positive breast
      cancer, is converted to its active metabolites, Z- and Z'-endoxifen and 4-OH-Tam
      isomers, primarily by cytochrome P450 CYP2D6. In 117 patients taking 20 mg/day of
      Tam, we determined CYP2D6 genotypes and measured the plasma levels of Tam
      metabolites. The Z-endoxifen levels increased while Z'-endoxifen levels decreased
      with increasing metabolizer phenotype activity (MPA) score (P <= 0.0004). The
      dosage in patients with endoxifen <40 nmol/l and/or CYP2D6 MPA scores of 0 was
      increased to 30 mg/day and their metabolite isomers were monitored for up to 90
      days. Of the 24 patients on the increased dose, 90% showed an increase in active
      isomers by day 60; the rate of increase correlated with the MPA score. Notably,
      their antiestrogenic activity scores (AASs), which estimate total isomer biologic
      activity, increased from a baseline median of 17 to 26 at day 60. Further studies
      involving increasing/decreasing the Tam dosage based on the AAS may determine
      whether dose adjustment can optimize treatment and improve long-term survival.

PMID- 21900891
TI  - Clinical Pharmacogenetics Implementation Consortium Guidelines for CYP2C9 and
      VKORC1 genotypes and warfarin dosing.
AB  - Warfarin is a widely used anticoagulant with a narrow therapeutic index and large
      interpatient variability in the dose required to achieve target anticoagulation.
      Common genetic variants in the cytochrome P450-2C9 (CYP2C9) and vitamin K-epoxide
      reductase complex (VKORC1) enzymes, in addition to known nongenetic factors,
      account for ~50% of warfarin dose variability. The purpose of this article is to
      assist in the interpretation and use of CYP2C9 and VKORC1 genotype data for
      estimating therapeutic warfarin dose to achieve an INR of 2-3, should genotype
      results be available to the clinician. The Clinical Pharmacogenetics
      Implementation Consortium (CPIC) of the National Institutes of Health
      Pharmacogenomics Research Network develops peer-reviewed gene-drug guidelines
      that are published and updated periodically on http://www.pharmgkb.org based on
      new developments in the field.(1).

PMID- 21900892
TI  - From treating complex coronary artery disease to promoting cardiovascular health:
      therapeutic transitions and challenges, 2010-2020.
AB  - Cardiovascular disease (CVD) has become the most common cause of mortality
      worldwide. Obesity, insufficient physical exercise, diabetes, and advancing age
      are major risk factors for developing cardiovascular disease that are currently
      increasing in prevalence. Nevertheless, significant progress has recently been
      made in the treatment of complex cardiovascular and coronary artery disease
      (CAD), with pharmacological management set to assume an increasingly important
      role. Other timely factors, such as the development of the polypill and high
      level medical and political interest in advancing cardiovascular health, are
      driving forces that may help to make inroads into the global cardiovascular
      disease burden. In this article, we critically review the key challenges that we
      face in the coming decade as we strive to transition and apply our growing
      knowledge of complex CAD to promoting global cardiovascular health.

PMID- 21900884
TI  - Review of pharmacological treatment in mood disorders and future directions for
      drug development.
AB  - After a series of serendipitous discoveries of pharmacological treatments for
      mania and depression several decades ago, relatively little progress has been
      made for novel hypothesis-driven drug development in mood disorders.
      Multifactorial etiologies of, and lack of a full understanding of, the core
      neurobiology of these conditions clearly have contributed to these development
      challenges. There are, however, relatively novel targets that have raised
      opportunities for progress in the field, such as glutamate and cholinergic
      receptor modulators, circadian regulators, and enzyme inhibitors, for alternative
      treatment. This review will discuss these promising new treatments in mood
      disorders, the underlying mechanisms of action, and critical issues of their
      clinical application. For these new treatments to be successful in clinical
      practice, it is also important to design innovative clinical trials that identify
      the specific actions of new drugs, and, ideally, to develop biomarkers for
      monitoring individualized treatment response. It is predicted that future drug
      development will identify new agents targeting the molecular mechanisms involved
      in the pathophysiology of mood disorders.

PMID- 21900893
TI  - SUMO1-dependent modulation of SERCA2a in heart failure.
AB  - The calcium-transporting ATPase ATP2A2, also known as SERCA2a, is a critical
      ATPase responsible for Ca(2+) re-uptake during excitation-contraction coupling.
      Impaired Ca(2+) uptake resulting from decreased expression and reduced activity
      of SERCA2a is a hallmark of heart failure. Accordingly, restoration of SERCA2a
      expression by gene transfer has proved to be effective in improving cardiac
      function in heart-failure patients, as well as in animal models. The small
      ubiquitin-related modifier (SUMO) can be conjugated to lysine residues of target
      proteins, and is involved in many cellular processes. Here we show that SERCA2a
      is SUMOylated at lysines 480 and 585 and that this SUMOylation is essential for
      preserving SERCA2a ATPase activity and stability in mouse and human cells. The
      levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in
      failing hearts. SUMO1 restitution by adeno-associated-virus-mediated gene
      delivery maintained the protein abundance of SERCA2a and markedly improved
      cardiac function in mice with heart failure. This effect was comparable to
      SERCA2A gene delivery. Moreover, SUMO1 overexpression in isolated cardiomyocytes
      augmented contractility and accelerated Ca(2+) decay. Transgene-mediated SUMO1
      overexpression rescued cardiac dysfunction induced by pressure overload
      concomitantly with increased SERCA2a function. By contrast, downregulation of
      SUMO1 using small hairpin RNA (shRNA) accelerated pressure-overload-induced
      deterioration of cardiac function and was accompanied by decreased SERCA2a
      function. However, knockdown of SERCA2a resulted in severe contractile
      dysfunction both in vitro and in vivo, which was not rescued by overexpression of
      SUMO1. Taken together, our data show that SUMOylation is a critical post
      translational modification that regulates SERCA2a function, and provide a
      platform for the design of novel therapeutic strategies for heart failure.

PMID- 21900894
TI  - Polyamine sensing by nascent ornithine decarboxylase antizyme stimulates decoding
      of its mRNA.
AB  - Polyamines are essential organic polycations with multiple cellular functions
      relevant for cell division, cancer and ageing. Regulation of polyamine synthesis
      is mainly achieved by controlling the activity of ornithine decarboxylase (ODC)
      through an unusual mechanism involving ODC antizyme, the binding of which
      disrupts homodimeric ODC and targets it for ubiquitin-independent degradation by
      the 26S proteasome. Whereas mammals express several antizyme genes, we have
      identified a single orthologue, termed OAZ1, in Saccharomyces cerevisiae. Similar
      to its mammalian counterparts, OAZ1 synthesis is induced with rising
      intracellular polyamine concentrations, which also inhibit ubiquitin-dependent
      degradation of the OAZ1 protein. Together, these mechanisms contribute to a
      homeostatic feedback regulation of polyamines. Antizyme synthesis involves a
      conserved +1 ribosomal frameshifting (RFS) event at an internal STOP codon during
      decoding of its messenger RNA. Here we used S. cerevisiae OAZ1 to dissect the
      enigmatic mechanism underlying polyamine regulation of RFS. In contrast with
      previous assumptions, we report here that the nascent antizyme polypeptide is the
      relevant polyamine sensor that operates in cis to negatively regulate upstream
      RFS on the polysomes, where its own mRNA is being translated. At low polyamine
      levels, the emerging antizyme polypeptide inhibits completion of its synthesis
      causing a ribosome pile-up on antizyme mRNA, whereas polyamine binding to nascent
      antizyme promotes completion of its synthesis. Thus, our study reveals a novel
      autoregulatory mechanism, in which binding of a small metabolite to a nascent
      sensor protein stimulates the latter's synthesis co-translationally.

PMID- 21900897
TI  - Get it together.

PMID- 21900895
TI  - Widespread iron-rich conditions in the mid-Proterozoic ocean.
AB  - The chemical composition of the ocean changed markedly with the oxidation of the
      Earth's surface, and this process has profoundly influenced the evolutionary and
      ecological history of life. The early Earth was characterized by a reducing ocean
      atmosphere system, whereas the Phanerozoic eon (less than 542 million years ago)
      is known for a stable and oxygenated biosphere conducive to the radiation of
      animals. The redox characteristics of surface environments during Earth's middle
      age (1.8-1 billion years ago) are less well known, but it is generally assumed
      that the mid-Proterozoic was home to a globally sulphidic (euxinic) deep ocean.
      Here we present iron data from a suite of mid-Proterozoic marine mudstones.
      Contrary to the popular model, our results indicate that ferruginous (anoxic and
      Fe(2+)-rich) conditions were both spatially and temporally extensive across
      diverse palaeogeographic settings in the mid-Proterozoic ocean, inviting new
      models for the temporal distribution of iron formations and the availability of
      bioessential trace elements during a critical window for eukaryotic evolution.

PMID- 21900896
TI  - Derivation of haploid embryonic stem cells from mouse embryos.
AB  - Most animals are diploid, but haploid-only and male-haploid (such as honeybee and
      ant) species have been described. The diploid genomes of complex organisms limit
      genetic approaches in biomedical model species such as mice. To overcome this
      problem, experimental induction of haploidy has been used in fish. Haploid
      development in zebrafish has been applied for genetic screening. Recently,
      haploid pluripotent cell lines from medaka fish (Oryzias latipes) have also been
      established. In contrast, haploidy seems less compatible with development in
      mammals. Although haploid cells have been observed in egg cylinder stage
      parthenogenetic mouse embryos, most cells in surviving embryos become diploid.
      Here we describe haploid mouse embryonic stem cells and show their application in
      forward genetic screening.

PMID- 21900898
TI  - Cheap drugs pulled despite wealth gap in middle-income countries.

PMID- 21900899
TI  - Combination products neglected by FDA device evaluation.

PMID- 21900900
TI  - FDA reorganization inspires hope for better coordination.

PMID- 21900901
TI  - Proposed centralization of trial oversight stirs mixed reaction.

PMID- 21900902
TI  - French law to make conflict of interest disclosure mandatory.

PMID- 21900903
TI  - Patent protection brings hope to insurers.

PMID- 21900904
TI  - Nonprofit disease groups earmark grants for drug repositioning.

PMID- 21900905
TI  - PrEP trial successes prompt cost-effectiveness questions.

PMID- 21900906
TI  - US budget quagmire leaves global health funding in the lurch.

PMID- 21900907
TI  - Straight talk with...Alexander von Gabain. Interview by Hannah Waters.

PMID- 21900909
TI  - Taking tissue engineering to heart.

PMID- 21900910
TI  - Consistent clinical research standards benefit patients around the world.

PMID- 21900912
TI  - Tissue-specific adult stem cells in the human lung.

PMID- 21900913
TI  - Paraoxonase-1 and clopidogrel efficacy.

PMID- 21900914
TI  - Paraoxonase-1 and clopidogrel efficacy.

PMID- 21900915
TI  - Paraoxonase-1 and clopidogrel efficacy.

PMID- 21900917
TI  - A new twist in the function of the cardiac lipid droplet.

PMID- 21900918
TI  - Cancer stem cells renew their impact.

PMID- 21900919
TI  - The social aspects of EMT-MET plasticity.

PMID- 21900920
TI  - Anticancer effects of imatinib via immunostimulation.

PMID- 21900921
TI  - Starting the scar: a primary role for pericytes?

PMID- 21900922
TI  - Autoimmunity's collateral damage: Immunodeficiency hints at autoreactivity to
      cytokines.

PMID- 21900923
TI  - Autoimmunity's collateral damage: Gut microbiota strikes 'back'.

PMID- 21900936
TI  - Resolving controversies on the path to Alzheimer's therapeutics.
AB  - Alzheimer's disease constitutes a personal and societal tragedy of immense
      proportions. Since 1960, research in laboratories and clinics worldwide has
      elucidated many features of this insidious and ultimately fatal syndrome, and
      this progress has led to initial human trials of potentially disease-modifying
      agents. However, some of these agents have already failed. Gnawing controversies
      and important gaps in our knowledge seem to cast additional doubt on the ability
      of the field to move forward effectively. Here I discuss some of these looming
      concerns and offer possible explanations for the major trial failures that
      suggest they are not predictive of the future. Rigorous preclinical validation of
      mechanism-based therapeutic agents followed by meticulously designed trials that
      focus on the cardinal cognitive symptoms and their associated biomarkers in the
      mild or presymptomatic phases of Alzheimer's disease are likely to lead to
      success, perhaps in the not-too-distant future.

PMID- 21900940
TI  - Chronic kidney disease in postmenopausal women.
AB  - Menopause is derived from the Greek words men (month) and pauses (cessation) and
      means permanent cessation of menstruation after the loss of ovarian activity.
      Chronic kidney disease (CKD) has recently been associated with cardiovascular
      events in several studies. CKD patients have a heavy burden of traditional
      cardiovascular risk factors in addition to a range of nontraditional risk factors
      such as inflammation and abnormal metabolism of calcium and phosphate. In this
      review, the association of CKD and cardiovascular disease (CVD), as well as of
      osteoporosis in postmenopausal women is discussed. CKD mineral and bone disorder,
      characterized by disturbances of calcium/phosphate/parathyroid hormone, bone
      abnormalities and vascular and soft tissue calcification, is highly prevalent in
      CKD and is a strong, independent predictor of bone fracture, CVD and death.
      Estrogen has been shown to: (a) decrease the expression of angiotensin type 1
      receptors in vasculature and kidneys; (b) reduce the expression and activity of
      angiotensin-converting enzyme, and (c) cause the release of angiotensinogen
      substrate from the liver. However, the degree of activation or suppression of the
      renin-angiotensin-aldosterone system by estrogen has not been clearly
      established. Clinical data on the effects of estrogen therapy on bone mineral
      densities are extremely limited in the ESRD population. CVD is the most common
      cause of death in postmenopausal women with CKD and many contributing factors
      have been explored. Future research for prevention of CVD in postmenopausal women
      with CKD would focus on the biology of vascular calcification as well as bone
      loss.

PMID- 21900941
TI  - Efficacy and safety of aliskiren, a direct renin inhibitor, compared with
      ramipril in Asian patients with mild to moderate hypertension.
AB  - This 8-week, randomized, double-blind, parallel-group study compared the efficacy
      and safety of aliskiren with ramipril in Asian patients with mild to moderate
      hypertension. Following a 2- to 3-week placebo run-in period, patients with mean
      sitting diastolic blood pressure (msDBP) >=95 and <110 mm Hg were randomized to
      receive once daily dose of either aliskiren 75, 150, 300 mg or ramipril 5 mg for
      8 weeks. Efficacy variables were the changes in msDBP and mean sitting systolic
      BP (msSBP) and BP control rates (<140/90 mm Hg). Safety was assessed by recording
      adverse events (AEs) and serious AEs (SAEs). Of 1316 randomized patients, 1160
      (88.1%) completed the study. At the study endpoint, patients on aliskiren had
      greater mean BP reductions (14.39/11.63 mm Hg for 300 mg; 12.16/10.04 mm Hg for
      150 mg; 12.24/10.66 mm Hg for 75 mg) than those on 5 mg ramipril (11.46/9.19 mm
      Hg). All aliskiren doses were statistically non-inferior (P<0.0001) to ramipril
      in reducing msDBP. The reduction in BP for aliskiren 300 mg was statistically
      superior vs. ramipril (P<0.002). Blood pressure control rates were higher for
      aliskiren (300 mg, 52.29%; 150 mg, 48.11%; 75 mg, 45.68%) than for ramipril (5
      mg, 43.7%); the difference for aliskiren 300 mg vs. ramipril 5 mg was
      statistically significant (P<0.05). Aliskiren was well tolerated with a fourfold
      lower incidence of cough (0.6-1.2%) compared with ramipril (5.2%). SAEs were rare
      in this study (0.5%). Aliskiren produced greater BP reductions with a lower
      incidence of cough than ramipril in Asian patients with mild to moderate
      hypertension.

PMID- 21900943
TI  - Role of brainstem thyrotropin-releasing hormone-triggered sympathetic
      overactivation in cardiovascular mortality in type 2 diabetic Goto-Kakizaki rats.
AB  - Sympathetic hyperactivity has an important role in cardiovascular mortality in
      patients with type 2 diabetes (T2D). Thyrotropin-releasing hormone (TRH)
      containing fibers innervate autonomic motor and premotor nuclei of the brainstem
      and spinal cord that regulate cardiovascular functions. We compared
      cardiovascular responses to application of TRH-analog in the brainstem of Wistar
      and T2D Goto-Kakizaki (GK) rats. GK rats exhibited basal systolic hypertension
      (152+/-2 mm Hg) and had a significantly potentiated, dose-related hypertensive
      response to intracisternal (i.c.) injection of the TRH-analog RX77368 (10-60 ng).
      In GK rats only, i.c. RX77368 (30-60 ng) markedly increased heart rate (HR; +88
      b.p.m.) and induced acute cardiac mortality (100%), concurrent with extreme
      hyperglycemia (>26 mmol l(-1)), increased plasma H(2)O(2) and 8-isoprostane, and
      enhanced heart expression of NADPH oxidase 4 and vascular cell adhesion molecule
      1 mRNAs. GK rats also had elevated basal plasma epinephrine, higher adrenal gene
      expression of tyrosine hydroxylase and dopamine beta-hydroxylase (DbetaH), and
      greater plasma catecholamine and adrenal DbetaH responses to i.c. TRH-analog,
      compared with Wistar rats. In GK rats, hexamethonium blocked i.c. RX77368-induced
      hypertensive and tachycardic responses, and reduced mortality by 86%, whereas
      phentolamine abolished the hypertensive response but enhanced tachycardia (+160
      b.p.m.), and reduced mortality by 50%. The angiotensin II type 1 receptor
      antagonist irbesartan prevented i.c. RX77368-induced increases in blood pressure,
      HR and mortality. In conclusion, sympathetic overactivation triggered by
      brainstem TRH contributes to the mechanism of cardiovascular morbidity and
      mortality in T2D, which involves heightened cardiac inflammation and peripheral
      oxidative stress responses to sympathetic drive, and a mediating role of the
      renin-angiotensin system.

PMID- 21900942
TI  - Losartan modulates muscular capillary density and reverses thiazide diuretic
      exacerbated insulin resistance in fructose-fed rats.
AB  - The renin-angiotensin system (RAS) is involved in the pathogenesis of insulin
      sensitivity (IS). The role of RAS in insulin resistance and muscular circulation
      has yet to be elucidated. Therefore, this study sought to determine the
      mechanisms of angiotensin II receptor blockers (ARBs) and/or diuretics on IS and
      capillary density (CD) in fructose-fed rats (FFRs). Sprague-Dawley rats were fed
      either normal chow (control group) or fructose-rich chow for 8 weeks. For the
      last 4 weeks, FFRs were allocated to four groups: an FFR group and groups treated
      with the thiazide diuretic hydrochlorothiazide (HCTZ), with the ARB losartan, or
      both. IS was evaluated by the euglycemic hyperinsulinemic glucose clamp technique
      at week 8. In addition, CD in the extensor digitorum longus muscle was evaluated.
      Blood pressure was significantly higher in the FFRs than in the controls. HCTZ,
      losartan and their combination significantly lowered blood pressure. IS was
      significantly lower in the FFR group than in the controls and was even lower in
      the HCTZ group. Losartan alone or combined with HCTZ significantly increased IS.
      In all cases, IS was associated with muscular CD, but not with plasma adiponectin
      or lipids. These results indicate that losartan reverses HCTZ-exacerbated insulin
      resistance, which can be mediated through the modulation of muscular circulation
      in rats with impaired glucose metabolism.

PMID- 21900945
TI  - Y-chromosome haplogroup diversity in the sub-Himalayan Terai and Duars
      populations of East India.
AB  - The sub-Himalayan Terai and Duars, the important outermost zones comprising the
      plains of East India, are known as the reservoirs of ethnic diversity. Analysis
      of the paternal genetic diversity of the populations inhabiting these regions and
      their genetic relationships with adjacent Himalayan and other Asian populations
      has not been addressed empirically. In the present investigation, we undertook a
      Y-chromosome phylogeographic study on 10 populations (n=375) representing four
      different linguistic groups from the sub-Himalayan Terai and Duars regions of
      East India. The high-resolution analysis of Y-chromosome haplogroup variations
      based on 76 binary markers revealed that the sub-Himalayan paternal gene pool is
      extremely heterogeneous. Three major haplogroups, namely H, O and R, are shared
      across the four linguistic groups. The Indo-European-speaking castes exhibit more
      haplogroup diversity than the tribal groups. The findings of the present
      investigation suggest that the sub-Himalayan gene pools have received predominant
      Southeast Asian contribution. In addition, the presence of Northeast and South
      Asian signatures illustrate multiple events of population migrations as well as
      extensive genetic admixture amongst the linguistic groups.

PMID- 21900944
TI  - Genome-wide association study identifies genetic variants in GOT1 determining
      serum aspartate aminotransferase levels.
AB  - We carried out a genome-wide association study of serum aspartate
      aminotransferase (AST) activity in 866 Amish participants of the Heredity and
      Phenotype Intervention Heart Study and identified significant association of AST
      activity with a cluster of single nucleotide polymorphisms located on chromosome
      10q24.1 (peak association was rs17109512; P=2.80E-14), in the vicinity of GOT1,
      the gene encoding cytosolic AST (cAST). Sequencing of GOT1 revealed an in-frame
      deletion of three nucleic acids encoding asparagine at position 389
      c.1165_1167delAAC (p.Asn389del) in the gene. Deletion carriers had significantly
      lower AST activity levels compared with homozygotes for the common allele (mean+/
      s.d.: 10.0+/-2.8 versus 18.8+/-5.2 U l(-1); P=2.80E-14). Further genotyping of
      the deletion in other Amish samples (n=1932) identified an additional 20 carriers
      (minor allele frequency (MAF)=0.0052). The deletion was not detected in 647
      outbred Caucasians. Asn at codon 389 is conserved among known mammalian cASTs. In
      vitro transient transfection of wild-type and mutant cAST indicated that mutant
      cAST protein was barely detectable in the cells. Furthermore, even after
      correction for cAST expression, mutant cAST had markedly diminished enzymatic
      activity. Remarkably, we did not find any association between the deletion and
      metabolic traits including serum fasting glucose or insulin, fasting and post
      meal lipids, inflammatory markers, or sub-clinical markers of cardiovascular
      disease. In conclusion, we discovered a rare in-frame deletion in GOT1 gene,
      which inactivates cAST enzyme in the Old Order Amish. This finding will help us
      to understand structure and function of the enzyme and would be useful for
      predicting serum AST levels.

PMID- 21900946
TI  - Identification of independent risk loci for Graves' disease within the MHC in the
      Japanese population.
AB  - To identify genetic variants that confer the risk of Graves' disease (GD) in the
      Japanese population, we conducted a two-stage genome-wide association study
      (GWAS) using 1119 Japanese individuals with GD and 2718 unrelated controls, and a
      subsequent replication study using independent 432 GD cases and 1157 controls. We
      identified 34 single nucleotide polymorphisms (SNPs) to be significantly
      associated with GD in the GWAS phase. Twenty-two out of 34 SNPs remained positive
      in the replication study. All 22 SNPs were located within the major
      histocompatibility complex (MHC) locus on chromosome 6p21. No strong long-range
      linkage disequilibrium (LD) was observed among the 22 SNPs, indicating
      independent involvement of multiple loci within the MHC with the risk of GD.
      Multivariate stepwise logistic regression analysis selected rs3893464, rs4313034,
      rs3132613, rs4248154, rs2273017, rs9394159 and rs4713693, as markers for
      independent risk loci for GD. The analysis of LD between these seven SNPs and
      tagging SNPs for GD-associated human leukocyte antigen (HLA) alleles in the
      Japanese population (HLA-DPB1(*)0501 and HLA-A(*)0206) demonstrated that all of
      and five of seven SNPs were not in strong LD with HLA-DPB1(*)0501 and HLA
      A(*)0206, respectively. Although causal variants remain to be identified, our
      results demonstrate the existence of multiple GD susceptibility loci within the
      MHC region.

PMID- 21900948
TI  - Survivin: a dual player in healthy and diseased skin.
AB  - Survivin belongs to the inhibitor of apoptosis (IAP) protein family, and, in
      addition to the antiapoptotic functions, it also regulates the cell cycle. The
      survivin gene generates five major isoforms with diverse and opposite functions.
      Survivin is highly expressed in cancer and in few normal adult tissues, including
      skin. It is mostly detected in the nucleus of keratinocyte stem cells (KSCs), but
      it is also expressed in melanocytes and fibroblasts. Survivin isoforms are
      differentially detected in subpopulations of human keratinocytes, exerting
      contrasting activities. Survivin has an important role in the regulation of cell
      cycle in keratinocytes, and it protects these cells from anoikis and UV-induced
      apoptosis. In melanoma, survivin is abundantly expressed, and its subcellular
      localization varies depending upon tumor thickness and invasiveness. Survivin
      overexpression has been shown in squamous cell carcinoma (SCC), and it is also
      involved in UVB-induced carcinogenesis. The presence of survivin both in the
      nucleus and in the cytoplasm throughout the epidermal layers of psoriatic lesions
      suggests the involvement of this protein in the keratinocyte alterations typical
      of this disease. Additional studies on the expression of survivin isoforms and
      their subcellular localization in relation to function will confirm the key role
      of survivin in the skin and will open the field to new therapeutic strategies for
      many cutaneous conditions.

PMID- 21900947
TI  - GM-CSF-independent CD1a expression in epidermal Langerhans cells: evidence from
      human CD1A genome-transgenic mice.

PMID- 21900949
TI  - No evidence for association of HPyV6 or HPyV7 with different skin cancers.

PMID- 21900950
TI  - SLIT prevents the development of eczema in percutaneous allergen-sensitized mice.

PMID- 21900951
TI  - The dual effect of the lupus-associated polymorphism rs10516487 on BANK1 gene
      expression and protein localization.
AB  - Numerous loci have been found genetically associated with complex diseases, but
      only in a few cases has the functional variant and the molecular mechanism behind
      it been identified. Recently, the association of the BANK1 gene with systemic
      lupus erythematosus (SLE) was described. Here, we investigated the role of the
      associated polymorphisms on gene function and found that SNP rs17266594 located
      in the branch point consensus sequence has negligible effect on splicing or gene
      expression. The non-synonymous SNP rs10516487 located in exon 2 influenced
      splicing efficiency by creating an exonic splicing enhancer site for the SRp40
      factor. Further, this same SNP generates protein isoforms with differential and
      measurable self-association properties. The full-length protein isoform
      containing the R61 variant forms larger protein scaffold complexes in the cell
      cytoplasm compared with the protective BANK1-61H variant. We also observed that,
      contrary to the full-length isoforms, the short Delta2 isoform of BANK1 displays
      a homogeneous cytoplasmic distribution, underscoring the potential role of the
      exon 2-coded protein domain in the scaffolding function of BANK1. We provide
      evidence that the non-synonymous SNP rs10516487 (G>A; R61H) shows a dual nature
      by first, influencing mRNA splicing and consequently the quantity of protein,
      and, second, by producing a risk variant-containing protein isoform with
      increased potential for multimerization.

PMID- 21900952
TI  - A perfect replacement for the mercury sphygmomanometer: the case of the hybrid
      blood pressure monitor.
AB  - This study validated a hybrid mercury-free device as a replacement of the mercury
      sphygmomanometer for professional use, and also as a standard for future
      validations. A validation study was performed according to the European Society
      of Hypertension International Protocol 2010 (ESH-IP) in 33 subjects using
      simultaneous blood pressure (BP) measurements. A total of six BP measurements
      were taken per participant simultaneously by a supervisor (S; hybrid auscultatory
      device Nissei DM3000) and two observers (A and B; mercury sphygmomanometers). ESH
      IP analysis (99 BP readings): mean device-observer systolic/diastolic BP
      difference 0.2+/-2.0/0.1+/-2.0 mm Hg; systolic BP differences <=5/10/15 mm Hg in
      97/99/99 readings, respectively (diastolic 98/99/99). All 33 subjects had 2 of 3
      BP differences <=5 mm Hg and none without a difference <=5 mm Hg. Further
      analysis (198 BP readings): mean differences S-A 0.1+/-2.4/0.2+/-2.4 mm Hg
      (systolic/diastolic), S-B 0.3+/-2.1/0.2+/-2.2, A-B 0.2+/-2.4/0.0+/-2.3;
      differences <=2 mm Hg S-A in 88/84% (systolic/diastolic), S-B 87/85%, A-B 87/86%
      and <=4 mm Hg S-A 95/96%, S-B 95/96%, A-B 95/98%. In conclusion, a hybrid mercury
      free auscultatory BP monitor comfortably passed the ESH-IP 2010 requirements and
      has the same level of accuracy as the mercury sphygmomanometer. This device
      appears to be a reliable alternative to the mercury sphygmomanometer for
      professional use and also as a standard for future validations.

PMID- 21900953
TI  - To dip or not to dip? The unique relationship between different blood pressure
      patterns and cardiac function and structure.
AB  - Dipping and nondipping blood pressure (BP) patterns are associated with different
      levels of target organ damage and cardiovascular risk. The aim of our
      investigation was to determine the relationship between different BP patterns
      (dipping, nondipping, extreme dipping and reverse dipping type) and cardiac
      structure, and function in hypertensive patients. This cross-sectional study
      included 376 hypertensive patients. All subjects underwent 24-h ambulatory BP
      monitoring, and complete two-dimensional, pulsed and tissue Doppler
      echocardiography. Most of the parameters of the left ventricular (LV) diastolic
      function (E/A, e'/a', E/e') significantly and progressively deteriorated from the
      extreme dippers to the dippers and nondippers, and finally to the reverse
      dippers. In contrast, LV structural parameters (IVS, RWT, LV mass index) showed a
      statistically important difference only by comparing the dippers and the extreme
      dippers with the rest of the patients. Simultaneously, the right ventricular (RV)
      structural parameter (RVT, right ventricular thickness), and most RV diastolic
      parameters significantly and progressively worsened from the extreme dippers,
      over the dippers and the nondippers, to the reverse dippers. Daytime and night
      time systolic BP, nocturnal systolic BP fall, and the nondipping and the reverse
      dipping status were independently associated with LV and RV structure, as well as
      with diastolic function. LV and RV structure, and diastolic function were
      significantly more impaired with the nondippers and the reverse dippers compared
      with others.

PMID- 21900954
TI  - Aneuploidy stokes the fire.

PMID- 21900955
TI  - That's the theory.

PMID- 21900956
TI  - Cytokine cues.

PMID- 21900957
TI  - The evil curse of ocular pemphigoid.

PMID- 21900958
TI  - Essential requirement of cytochrome c release for caspase activation by
      procaspase-activating compound defined by cellular models.
AB  - Mitochondrial cytochrome c (cyt. c) release and caspase activation are often
      impaired in tumors with Bcl-2 overexpression or Bax and Bak-defective status.
      Direct triggering of cell death downstream of Bax and Bak is an attractive
      strategy to kill such cancers. Small molecule compounds capable of direct caspase
      activation appear to be the best mode for killing such tumors. However, there is
      no precise model to screen such compounds. The currently employed cell-free
      systems possess the inherent drawback of lacking cellular contents and organelles
      that operate in integrating cell death signaling. We have developed highly
      refined cell-based approaches to validate direct caspase activation in cancer
      cells. Using this approach, we show that PAC-1 (first procaspase-activating
      compound), the first direct activator of procaspases identified in a cell-free
      system, in fact requires mitochondrial cyt. c release for triggering caspase
      activation similar to other antitumor agents. It can induce significant caspase
      activation and cell death in the absence of Bax and Bak, and in cells
      overexpressing Bcl-2 and Bcl-xL. This study for the first time defines precise
      criteria for the validation of direct caspase-activating compounds using
      specialized cellular models that is expected to accelerate the discovery of
      potential direct caspase activators.

PMID- 21900959
TI  - CYLD regulates keratinocyte differentiation and skin cancer progression in
      humans.
AB  - CYLD is a gene mutated in familial cylindromatosis and related diseases, leading
      to the development of skin appendages tumors. Although the deubiquitinase CYLD is
      a skin tumor suppressor, its role in skin physiology is unknown. Using skin
      organotypic cultures as experimental model to mimic human skin, we have found
      that CYLD acts as a regulator of epidermal differentiation in humans through the
      JNK signaling pathway. We have determined the requirement of CYLD for the
      maintenance of epidermal polarity, keratinocyte differentiation and apoptosis. We
      show that CYLD overexpression increases keratinocyte differentiation while CYLD
      loss of function impairs epidermal differentiation. In addition, we describe the
      important role of CYLD in the control of human non-melanoma skin cancer
      progression. Our results show the reversion of the malignancy of human squamous
      cell carcinomas that express increased levels of CYLD, while its functional
      inhibition enhances the aggressiveness of these tumors which progress toward
      spindle cell carcinomas. We have found that the mechanisms through which CYLD
      regulates skin cancer progression include the control of tumor differentiation,
      angiogenesis and cell survival. These findings of the role of CYLD in human skin
      cancer prognosis make our results relevant from a therapeutic point of view, and
      open new avenues for exploring novel cancer therapies.

PMID- 21900961
TI  - Toxicity and exposure of an adenovirus containing human interferon alpha-2b
      following intracystic administration in cynomolgus monkeys.
AB  - The safety and toxicokinetics of SCH 721015, an adenovirus encoding the human
      interferon alpha-2b gene, and Syn3 (SCH 209702), a novel excipient, were assessed
      in cynomolgus monkeys administered intravesical doses of 2.5 * 10E11 or 1.25 *
      10E13 particles SCH 721015 in 25 mg Syn3 or 25 mg Syn3 alone on study days 1 and
      91. There was no systemic toxicity. Monkeys dosed with SCH 721015 in Syn3 were
      positive for SCH 721015-specific DNA in the urine for 2 to 3 days following each
      dose and had interferon alpha-2b protein in the urine for 1-3 days after a single
      dose and in fewer animals after a second dose. Intracystic administration was
      associated with inflammation and focal/multifocal ulceration in the urinary
      bladder and irritation in the ureters and urethra at necropsy. The physical
      trauma from catheterization and filling/emptying of the bladder was likely a
      contributing factor and Syn3 exacerbated the trauma. There was nearly complete
      resolution of these findings 2 months after the last dose. The trauma to the
      bladder likely contributed to low, transient systemic exposure to Syn3, SCH
      721015 and human interferon protein. The results of this study support the
      clinical investigation of SCH 721015 in Syn3.

PMID- 21900960
TI  - Serpina3n attenuates granzyme B-mediated decorin cleavage and rupture in a murine
      model of aortic aneurysm.
AB  - Granzyme B (GZMB) is a proapoptotic serine protease that is released by cytotoxic
      lymphocytes. However, GZMB can also be produced by other cell types and is
      capable of cleaving extracellular matrix (ECM) proteins. GZMB contributes to
      abdominal aortic aneurysm (AAA) through an extracellular, perforin-independent
      mechanism involving ECM cleavage. The murine serine protease inhibitor, Serpina3n
      (SA3N), is an extracellular inhibitor of GZMB. In the present study,
      administration of SA3N was assessed using a mouse Angiotensin II-induced AAA
      model. Mice were injected with SA3N (0-120 MUg/kg) before pump implantation. A
      significant dose-dependent reduction in the frequency of aortic rupture and death
      was observed in mice that received SA3N treatment compared with controls. Reduced
      degradation of the proteoglycan decorin was observed while collagen density was
      increased in the aortas of mice receiving SA3N treatment compared with controls.
      In vitro studies confirmed that decorin, which regulates collagen spacing and
      fibrillogenesis, is cleaved by GZMB and that its cleavage can be prevented by
      SA3N. In conclusion, SA3N inhibits GZMB-mediated decorin degradation leading to
      enhanced collagen remodelling and reinforcement of the adventitia, thereby
      reducing the overall rate of rupture and death in a mouse model of AAA.

PMID- 21900962
TI  - The combination of chemotherapy with HVJ-E containing Rad51 siRNA elicited
      diverse anti-tumor effects and synergistically suppressed melanoma.
AB  - Dacarbazine (DTIC) is one of the most popular alkylating agents used for the
      treatment of malignant melanoma. DTIC induces apoptosis of melanoma cells via
      double-strand breaks (DSBs). Melanoma cells, however, tend to increase their
      expression of DNA repair molecules in order to be resistant to DTIC. Here, we
      show that DTIC increases expression of Rad51, but not Ku70, in a cultured B16-F10
      mouse melanoma cell line in dose- and time-dependent manners. On introducing
      Rad51 short interfering RNA (siRNA) with the hemagglutinating virus of Japan
      envelope (HVJ-E) to B16-F10 cells, DSBs induced by DTIC treatment were not
      efficiently repaired and resulted in enhanced apoptotic cell death. Colony
      formation of B16-F10 cells that received Rad51 siRNA was significantly decreased
      by DTIC treatment as compared with cells that received scramble siRNA. In
      melanoma-bearing mice, the combination of three intratumoral injections of HVJ-E
      containing Rad51 siRNA and five intraperitoneal injections of DTIC at a clinical
      dose synergistically suppressed the tumors. Moreover, HVJ-E demonstrated anti
      tumor immunity by inducing cytotoxic T lymphocytes to B16-F10 cells on
      administration of DTIC. These results suggest that the combination of
      chemotherapy with HVJ-E containing therapeutic molecules will provide a promising
      therapeutic strategy for patients bearing malignant tumors resistant to
      chemotherapeutic agents.

PMID- 21900964
TI  - A retroviral vector suitable for ultrasound image-guided gene delivery to mouse
      brain.
AB  - Gene transfer to the early-stage embryonic brain using the ultrasound image
      guided gene delivery (UIGD) technique has proven to be valuable for investigating
      brain development. Thus far, this technology has been restricted to the study of
      embryonic neurogenesis. When this technique is designed to be employed for the
      study in adult animals, a long-term stable gene expression will be required. We
      attempted to develop a retroviral vector suitable for expressing exogenous genes
      in the brains of postnatal and adult mice in the context of the UIGD technique.
      Retroviral vectors containing four different long terminal repeats (LTRs) (each
      from Moloney murine leukemia virus (MoMLV), murine stem cell virus (MSCV),
      myeloproliferative sarcoma virus (MPSV) and spleen focus-forming virus (SFFV))
      were compared using the well-known CE vector having the EF1alpha internal
      promoter as a control. The MS vector containing MSCV LTR produced a higher viral
      titer and a higher level of gene expression than other vectors including CE. The
      MS vector drove the gene expression in cultured neural stem cells for 3 weeks.
      Furthermore, the MS vector could efficiently deliver the gene to the mouse
      central nervous system, as transgene expression was found in various regions of
      the brains and spinal cords as well as in all major neural cell types. The data
      from an in vivo luciferase imaging analysis showed that the gene expression from
      the MS vector was sustainable for almost 3 months. Our data suggested that the MS
      vector would be suitable to construct mice containing the transgene expressed in
      the brain or spinal cord in a quick and cost-effective manner.

PMID- 21900963
TI  - Imaging gene delivery in a mouse model of congenital neuronal ceroid
      lipofuscinosis.
AB  - Adeno-associated virus (AAV)-mediated gene replacement for lysosomal disorders
      have been spurred by the ability of some serotypes to efficiently transduce
      neurons in the brain and by the ability of lysosomal enzymes to cross-correct
      among cells. Here, we explored enzyme replacement therapy in a knock-out mouse
      model of congenital neuronal ceroid lipofuscinosis (NCL), the most severe of the
      NCLs in humans. The missing protease in this disorder, cathepsin D (CathD) has
      high levels in the central nervous system. This enzyme has the potential
      advantage for assessing experimental therapy in that it can be imaged using a
      near-infrared fluorescence (NIRF) probe activated by CathD. Injections of an
      AAV2/rh8 vector-encoding mouse CathD (mCathD) into both cerebral ventricles and
      peritoneum of newborn knock-out mice resulted in a significant increase in
      lifespan. Successful delivery of active CathD by the AAV2/rh8-mCathD vector was
      verified by NIRF imaging of mouse embryonic fibroblasts from knock-out mice in
      culture, as well as by ex vivo NIRF imaging of the brain and liver after gene
      transfer. These studies support the potential effectiveness and imaging
      evaluation of enzyme replacement therapy to the brain and other organs in CathD
      null mice via AAV-mediated gene delivery in neonatal animals.

PMID- 21900965
TI  - Enhanced pseudotyping efficiency of HIV-1 lentiviral vectors by a
      rabies/vesicular stomatitis virus chimeric envelope glycoprotein.
AB  - Rabies virus glycoprotein (RVG) can pseudotype lentiviral vectors, although at a
      lower efficiency to that of vesicular stomatitis virus glycoprotein (VSVG).
      Transduction with VSVG-pseudotyped vectors of rodent central nervous system (CNS)
      leads to local neurotropic gene transfer, whereas with RVG-pseudotyped vectors
      additional disperse transduction of neurons located at distal efferent sites
      occurs via axonal retrograde transport. Attempts to produce high-titre RVG
      pseudotyped lentiviral vectors for preclinical and clinical trials has to date
      been problematic. We have constructed several chimeric RVG/VSVG glycoproteins and
      found that a construct bearing the external/transmembrane domain of RVG and the
      cytoplasmic domain of VSVG shows increased incorporation onto HIV-1 lentiviral
      particles and has increased infectivity in vitro in 293T cells and in
      differentiated neuronal cell lines of human, rat and murine origin. Stereotactic
      application of vector pseudotyped with this RVG/VSVG chimera in the rat striatum
      resulted in efficient gene transfer at the site of injection showing both
      neuronal and glial tropism. Distal neuronal transduction in the substantia nigra,
      thalamus and olfactory bulb via retrograde axonal transport also occurs after
      intrastriatal administration of chimera-pseudotyped vectors at similar levels to
      that observed with a RVG-pseudotyped vector. This is the first report of distal
      transduction in the olfactory bulb. The enhanced pseudotyping with this envelope
      should enable easier production of higher-titre pseudotyped lentiviral vectors
      that exhibit efficient local and dispersed neuronal transduction in the CNS.

PMID- 21900966
TI  - Quorum sensing control of phosphorus acquisition in Trichodesmium consortia.
AB  - Colonies of the cyanobacterium Trichodesmium are abundant in the oligotrophic
      ocean, and through their ability to fix both CO(2) and N(2), have pivotal roles
      in the cycling of carbon and nitrogen in these highly nutrient-depleted
      environments. Trichodesmium colonies host complex consortia of epibiotic
      heterotrophic bacteria, and yet, the regulation of nutrient acquisition by these
      epibionts is poorly understood. We present evidence that epibiotic bacteria in
      Trichodesmium consortia use quorum sensing (QS) to regulate the activity of
      alkaline phosphatases (APases), enzymes used by epibionts in the acquisition of
      phosphate from dissolved-organic phosphorus molecules. A class of QS molecules,
      acylated homoserine lactones (AHLs), were produced by cultivated epibionts, and
      adding these AHLs to wild Trichodesmium colonies collected at sea led to a
      consistent doubling of APase activity. By contrast, amendments of (S)-4,5
      dihydroxy-2,3-pentanedione (DPD)-the precursor to the autoinducer-2 (AI-2) family
      of universal interspecies signaling molecules-led to the attenuation of APase
      activity. In addition, colonies collected at sea were found by high performance
      liquid chromatography/mass spectrometry to contain both AHLs and AI-2. Both types
      of molecules turned over rapidly, an observation we ascribe to quorum quenching.
      Our results reveal a complex chemical interplay among epibionts using AHLs and AI
      2 to control access to phosphate in dissolved-organic phosphorus.

PMID- 21900967
TI  - An all-taxon microbial inventory of the Moorea coral reef ecosystem.
AB  - The Moorea Coral Reef Long Term Ecological Research (LTER) Site (17.50 degrees S,
      149.83 degrees W) comprises the fringe of coral reefs and lagoons surrounding the
      volcanic island of Moorea in the Society Islands of French Polynesia. As part of
      our Microbial Inventory Research Across Diverse Aquatic LTERS biodiversity
      inventory project, we characterized microbial community composition across all
      three domains of life using amplicon pyrosequencing of the V6 (bacterial and
      archaeal) and V9 (eukaryotic) hypervariable regions of small-subunit ribosomal
      RNA genes. Our survey spanned eight locations along a 130-km transect from the
      reef lagoon to the open ocean to examine changes in communities along inshore to
      offshore gradients. Our results illustrate consistent community differentiation
      between inshore and offshore ecosystems across all three domains, with greater
      richness in all domains in the reef-associated habitats. Bacterial communities
      were more homogenous among open ocean sites spanning >100 km than among inshore
      sites separated by <1 km, whereas eukaryotic communities varied more offshore
      than inshore, and archaea showed more equal levels of dissimilarity among
      subhabitats. We identified signature communities representative of specific
      geographic and geochemical milieu, and characterized co-occurrence patterns of
      specific microbial taxa within the inshore ecosystem including several bacterial
      groups that persist in geographical niches across time. Bacterial and archaeal
      communities were dominated by few abundant taxa but spatial patterning was
      consistent through time and space in both rare and abundant communities. This is
      the first in-depth inventory analysis of biogeographic variation of all three
      microbial domains within a coral reef ecosystem.

PMID- 21900968
TI  - Using network analysis to explore co-occurrence patterns in soil microbial
      communities.
AB  - Exploring large environmental datasets generated by high-throughput DNA
      sequencing technologies requires new analytical approaches to move beyond the
      basic inventory descriptions of the composition and diversity of natural
      microbial communities. In order to investigate potential interactions between
      microbial taxa, network analysis of significant taxon co-occurrence patterns may
      help to decipher the structure of complex microbial communities across spatial or
      temporal gradients. Here, we calculated associations between microbial taxa and
      applied network analysis approaches to a 16S rRNA gene barcoded pyrosequencing
      dataset containing >160 000 bacterial and archaeal sequences from 151 soil
      samples from a broad range of ecosystem types. We described the topology of the
      resulting network and defined operational taxonomic unit categories based on
      abundance and occupancy (that is, habitat generalists and habitat specialists).
      Co-occurrence patterns were readily revealed, including general non-random
      association, common life history strategies at broad taxonomic levels and
      unexpected relationships between community members. Overall, we demonstrated the
      potential of exploring inter-taxa correlations to gain a more integrated
      understanding of microbial community structure and the ecological rules guiding
      community assembly.

PMID- 21900969
TI  - Heavy weather.

PMID- 21900970
TI  - A very Turkish coup.

PMID- 21900971
TI  - Brain burdens.

PMID- 21900972
TI  - Embrace failure to start up success.

PMID- 21900984
TI  - Fukushima impact is still hazy.

PMID- 21900985
TI  - NIH centre faces spell in limbo.

PMID- 21900986
TI  - Jumpy stars slow hunt for other Earths.

PMID- 21900987
TI  - Venus scientists fear neglect.

PMID- 21900988
TI  - A radical approach to mental illness. Interview by Alison Abbott.

PMID- 21900989
TI  - Climate and weather: Extreme measures.

PMID- 21900990
TI  - Biodefence since 9/11: The price of protection.

PMID- 21900991
TI  - Science since 9/11: Homeland insecurity.

PMID- 21900992
TI  - Debt crisis: Crunch time for US science.

PMID- 21900996
TI  - Q&A: Mr sustainability. Interview by Nicola Jones.

PMID- 21900997
TI  - Flagging flora: heart disease link.

PMID- 21900998
TI  - Research foundations: US private funder on indirect costs.

PMID- 21900999
TI  - Flagging flora: help from bacteriocins?

PMID- 21901000
TI  - Eco-indicators: Improve China's sustainability targets.

PMID- 21901001
TI  - Astrophysics: Broad escape from the abyss.

PMID- 21901002
TI  - Neuroscience: When lights take the circuits out.

PMID- 21901003
TI  - Metabolism: Let them eat fat.

PMID- 21901005
TI  - Geoscience: Earth's patchy late veneer.

PMID- 21901006
TI  - Cancer: Let sleeping DNA lie.

PMID- 21901007
TI  - BRCA1 tumour suppression occurs via heterochromatin-mediated silencing.
AB  - Mutations in the tumour suppressor gene BRCA1 lead to breast and/or ovarian
      cancer. Here we show that loss of Brca1 in mice results in transcriptional de
      repression of the tandemly repeated satellite DNA. Brca1 deficiency is
      accompanied by a reduction of condensed DNA regions in the genome and loss of
      ubiquitylation of histone H2A at satellite repeats. BRCA1 binds to satellite DNA
      regions and ubiquitylates H2A in vivo. Ectopic expression of H2A fused to
      ubiquitin reverses the effects of BRCA1 loss, indicating that BRCA1 maintains
      heterochromatin structure via ubiquitylation of histone H2A. Satellite DNA de
      repression was also observed in mouse and human BRCA1-deficient breast cancers.
      Ectopic expression of satellite DNA can phenocopy BRCA1 loss in centrosome
      amplification, cell-cycle checkpoint defects, DNA damage and genomic instability.
      We propose that the role of BRCA1 in maintaining global heterochromatin integrity
      accounts for many of its tumour suppressor functions.

PMID- 21901008
TI  - An origin of the radio jet in M87 at the location of the central black hole.
AB  - Powerful radio jets from active galactic nuclei are thought to be powered by the
      accretion of material onto the supermassive black hole (the 'central engine').
      M87 is one of the closest examples of this phenomenon, and the structure of its
      jet has been probed on a scale of about 100 Schwarzschild radii (R(s), the radius
      of the event horizon). However, the location of the central black hole relative
      to the jet base (a bright compact radio 'core') remains elusive. Observations of
      other jets indicate that the central engines are located about 10(4)-10(6)R(s)
      upstream from the radio core. Here we report radio observations of M87 at six
      frequencies that allow us to achieve a positional accuracy of about 20
      microarcseconds. As the jet base becomes more transparent at higher frequencies,
      the multifrequency position measurements of the radio core enable us to determine
      the upstream end of the jet. The data reveal that the central engine of M87 is
      located within 14-23R(s) of the radio core at 43 GHz. This implies that the site
      of material infall onto the black hole and the eventual origin of the jet reside
      in the bright compact region seen on the image at 43 GHz.

PMID- 21901009
TI  - Magnetic-field-induced charge-stripe order in the high-temperature superconductor
      YBa2Cu3Oy.
AB  - Electronic charges introduced in copper-oxide (CuO(2)) planes generate high
      transition-temperature (T(c)) superconductivity but, under special circumstances,
      they can also order into filaments called stripes. Whether an underlying tendency
      towards charge order is present in all copper oxides and whether this has any
      relationship with superconductivity are, however, two highly controversial
      issues. To uncover underlying electronic order, magnetic fields strong enough to
      destabilize superconductivity can be used. Such experiments, including quantum
      oscillations in YBa(2)Cu(3)O(y) (an extremely clean copper oxide in which charge
      order has not until now been observed) have suggested that superconductivity
      competes with spin, rather than charge, order. Here we report nuclear magnetic
      resonance measurements showing that high magnetic fields actually induce charge
      order, without spin order, in the CuO(2) planes of YBa(2)Cu(3)O(y). The observed
      static, unidirectional, modulation of the charge density breaks translational
      symmetry, thus explaining quantum oscillation results, and we argue that it is
      most probably the same 4a-periodic modulation as in stripe-ordered copper oxides.
      That it develops only when superconductivity fades away and near the same 1/8
      hole doping as in La(2-x)Ba(x)CuO(4) (ref. 1) suggests that charge order,
      although visibly pinned by CuO chains in YBa(2)Cu(3)O(y), is an intrinsic
      propensity of the superconducting planes of high-T(c) copper oxides.

PMID- 21901010
TI  - The tungsten isotopic composition of the Earth's mantle before the terminal
      bombardment.
AB  - Many precious, 'iron-loving' metals, such as gold, are surprisingly abundant in
      the accessible parts of the Earth, given the efficiency with which core formation
      should have removed them to the planet's deep interior. One explanation of their
      over-abundance is a 'late veneer'--a flux of meteorites added to the Earth after
      core formation as a 'terminal' bombardment that culminated in the cratering of
      the Moon. Some 3.8 billion-year-old rocks from Isua, Greenland, are derived from
      sources that retain an isotopic memory of events pre-dating this cataclysmic
      meteorite shower. These Isua samples thus provide a window on the composition of
      the Earth before such a late veneer and allow a direct test of its importance in
      modifying the composition of the planet. Using high-precision (less than 6 parts
      per million, 2 standard deviations) tungsten isotope analyses of these rocks,
      here we show that they have a isotopic tungsten ratio (182)W/(184)W that is
      significantly higher (about 13 parts per million) than modern terrestrial
      samples. This finding is in good agreement with the expected influence of a late
      veneer. We also show that alternative interpretations, such as partial remixing
      of a deep-mantle reservoir formed in the Hadean eon (more than four billion years
      ago) or core-mantle interaction, do not explain the W isotope data well. The
      decrease in mantle (182)W/(184)W occurs during the Archean eon (about four to
      three billion years ago), potentially on the same timescale as a notable decrease
      in (142)Nd/(144)Nd (refs 3 and 6). We speculate that both observations can be
      explained if late meteorite bombardment triggered the onset of the current style
      of mantle convection.

PMID- 21901014
TI  - Augmentation index association with reactive hyperemia as assessed by peripheral
      arterial tonometry in hypertension.
AB  - BACKGROUND: Augmentation pressure has emerged as a surrogate marker for
      cardiovascular disease, and endothelial dysfunction has been proposed as related
      factor. However, the relationship between augmentation pressure and digital
      endothelial function has not yet been well defined. We investigated the
      relationship between augmentation pressure and digital reactive hyperemia (RH) in
      patients with hypertension using peripheral arterial tonometry (PAT), which is
      regarded as being representative of endothelial function. METHODS: One hundred
      hypertensive patients (64 males; mean age, 49 +/- 12 years) without a history of
      taking antihypertensive medication were enrolled in this study. RESULTS: The mean
      augmentation pressure and augmentation index (AIx) normalized for a heart rate of
      75 beats/min (AIx75) were 15 +/- 8 mm Hg and 26 +/- 11%, respectively. The mean
      RH-PAT index and log transformed PAT ratio were 2.24 +/- 0.55 and 0.62 +/- 0.30.
      There was an inverse relationship between the RH-PAT index and age, male sex, and
      body mass index. The log transformed PAT ratio also showed inverse relationship
      with age and male sex. The RH-PAT index and the log transformed PAT ratio showed
      no relationship with augmentation pressure or AIx75. In a multiple linear
      regression analysis, age, height, and central systolic BP demonstrated an
      independent association with augmentation pressure and AIx75. CONCLUSION: In
      patients with hypertension, the RH-PAT index determined using PAT was not
      associated with augmentation pressure or AIx75. Digital vascular function may be
      a less important factor for pressure augmentation in patients with hypertension.

PMID- 21901015
TI  - Cell-penetrating peptides corresponding to the angiotensin II Type 1 receptor
      reduce receptor accumulation and cell surface expression and signaling.
AB  - BACKGROUND: Our previous published studies have established the gamma
      aminobutyric acid (GABA) receptor-associated protein (GABARAP) as a trafficking
      protein for the angiotensin II type 1A receptor (AT(1)R). GABARAP overexpression
      increases both AT(1)R protein accumulation and translocation to the plasma
      membrane. The present study examined the inhibitory effects of decoy peptides on
      receptor expression and plasma membrane accumulation. The decoy peptides
      correspond to the AT(1)R cytoplasmic domain located immediately proximal to the
      7th transmembrane domain, a region implicated in GABARAP binding. This
      competitive binding study was designed as a first step toward evaluating the
      GABARAP:AT(1)R binding interface as a target for reducing AT(1)R trafficking to
      the plasma membrane. METHODS: AT(1)R and GABARAP plasmids were transfected into
      mammalian cell lines simultaneously with cell-penetrating peptides (CPPs). CPP-1
      and CPP-2 consist of the penetratin (pANT(43-58)) CPP with downstream fusions of
      GKKFKKYFLQL (AT(1)R) and GKKFEEAFLQL (AT(1)R-mutant) amino acids, respectively.
      CPP-3 consists of the HIV TAT(48-60) CPP with GKKFKKYFLQL (AT(1)R) fused
      downstream. Western blotting, signal transduction studies, and 3D deconvolution
      microscopy experiments were employed. RESULTS: Immunoblot analyses and live cell
      deconvolution microscopy demonstrated that inhibitory (but not control) peptides
      completely blocked GABARAP-induced intracellular AT(1)R accumulation and cell
      surface accumulation. GABARAP also stimulated angiotensin II-mediated phospho
      ERK1/2 induction by ~ fivefold. This activation was, similarly, quantitatively
      blocked by the inhibitory peptides. CONCLUSIONS: Cell-penetrating decoy peptides
      which were designed to block the AT(1)R:GABARAP interaction, effectively reduced
      AT(1)R intracellular accumulation and cell-surface trafficking and signaling. The
      binding interaction site between AT(1)R and GABARAP represents a potential
      therapeutic target.

PMID- 21901016
TI  - Prostate cancer: intermediate-risk patients on radiotherapy benefit from addition
      of short-term ADT.

PMID- 21901017
TI  - Prostate cancer: DHT bypasses testosterone to drive progression to castration
      resistance.

PMID- 21901019
TI  - Kidney cancer: targeted therapy of glucose uptake via GLUT1 kills RCC cells.

PMID- 21901020
TI  - Bladder cancer: EMDA mitomycin before TURBT is the best treatment for non-muscle
      invasive disease.

PMID- 21901021
TI  - Bladder cancer: robot-assisted laparoscopic radical cystectomy: a single-center
      experience.

PMID- 21901022
TI  - Prostate cancer: postprostatectomy climacturia.

PMID- 21901023
TI  - Sexual dysfunction: penile revascularization has good long-term success rates.

PMID- 21901024
TI  - Sugar-sweetened and diet beverages in relation to visceral adipose tissue.
AB  - Frequent sugar-sweetened beverage (SSB) intake has been consistently associated
      with increased adiposity and cardio-metabolic risk, whereas the association with
      diet beverages is more mixed. We examined how these beverages associate with
      regional abdominal adiposity measures, specifically visceral adipose tissue
      (VAT). In a cross-sectional analysis of 791 non-Hispanic white men and women aged
      18-70 we examined how beverage consumption habits obtained from a food frequency
      questionnaire associate with overall and abdominal adiposity measures from MRI.
      With increasing frequency of SSB intake, we observed increases in waist
      circumference (WC) and the proportion of visceral to subcutaneous abdominal
      adipose tissue (VAT%), with no change in total body fat (TBF%) or BMI. Greater
      frequency of diet beverage intake was associated with greater WC, BMI, and TBF%,
      but was not associated with variation in visceral adiposity We conclude that
      increased frequency of SSB consumption is associated with a more adverse
      abdominal adipose tissue deposition pattern.

PMID- 21901025
TI  - Inflammation associated with obesity: relationship with blood and bone marrow
      endothelial cells.
AB  - The purpose of this study was to assess the inflammatory nature of obesity and
      its effect on blood and bone marrow endothelial cell populations. Obese patients
      (BMI >=30) had significantly higher concentrations of the inflammatory marker C
      reactive protein (CRP) (P = 0.03) and lower concentrations of the anti
      inflammatory cytokine interleukin-10 (IL-10) (P = 0.05). This cytokine profile is
      consistent with obesity being an inflammatory condition and is further supported
      by the significant correlation between total white blood cell count and BMI (r =
      0.15; P = 0.035). High BMI was associated with significantly lower numbers of
      early endothelial cells (CD45(-)/CD34(+)) in the bone marrow (r = -0.20; P =
      0.0068). There was also a significant inverse correlation between BMI and a more
      mature endothelial cell phenotype (CD45(-)/31(+)) in the blood (r = -0.17; P =
      0.02). In addition, there was a significant correlation between BMI- and
      endothelial-related cells of hematopoietic origin (CD133(+)/VEGFR-2(+)) in the
      bone marrow (r = -0.26; P = 0.0007). Patients with higher plasma IL-10 and
      insulin-like growth factor (IGF) concentrations had higher numbers of endothelial
      phenotypes in the bone marrow suggesting a protective effect of these anti
      inflammatory cytokines. In conclusion, this work confirms the inflammatory nature
      of obesity and is the first to report that obesity is associated with reduced
      endothelial cell numbers in the bone marrow of humans. These effects of obesity
      may be a potential mechanism for impaired tissue repair in obese patients.

PMID- 21901026
TI  - [Can we afford to become old?].

PMID- 21901027
TI  - Global health--a challenge for us all.

PMID- 21901028
TI  - [Yes to knowledge-based practice].

PMID- 21901029
TI  - [Evidence-based materials and independent physicians].

PMID- 21901030
TI  - [Two sides of the same thing?].

PMID- 21901032
TI  - [Dementia among younger persons and Huntington disease].

PMID- 21901034
TI  - [Incidence of stroke].

PMID- 21901035
TI  - [Do general practitioners follow the national guidelines for treating urinary
      tract infections with antibiotics?].
AB  - BACKGROUND: Incorrect use of antibiotics is a major public health concern both
      nationally and globally due to the development of antibiotic resistance. The goal
      of this study was to see if prescription of antibiotics for urinary tract
      infections in general practice was in accordance with national guidelines.
      MATERIAL AND METHODS: We combined two sets of data from February and March 2003:
      prescriptions of antibiotics redeemed in pharmacies, and electronic billing cards
      collected from the National Insurance Agency from 145 general practitioners in
      Vestfold county. We analysed all consultations related to urinary tract problems,
      and we found which antibiotics had been prescribed and for how long. The
      treatment was then compared with the national guidelines. A logistic regression
      analysis identified factors associated with adequate treatment length. RESULTS:
      Trimetoprime and mecillinam were most frequently prescribed to both genders.
      Sixty-nine (6 %) of the total 1,102 prescriptions were quinolones. A total of 271
      (32 %) of 847 patients who were prescribed antibiotics for cystitis did not get
      treatment of sufficient length. Female and young patients were more often given
      the correct duration of treatment. Doctors with 1,000-1,500 patients more
      frequently prescribed sufficiently long treatment compared to other physicians.
      Six patients (0.5 %) were prescribed another antibiotic between two and 14 days
      after the first prescription. CONCLUSION: The choice of antibiotics conformed
      well with national guidelines, but the duration of the treatment was often too
      short. In spite of this, only 0.5 % showed signs of relapse. A number of factors
      associated with adequate treatment length were identified. The empirical use of
      furadantin can be increased.

PMID- 21901036
TI  - [Post-exposure varicella prophylaxis].
AB  - BACKGROUND: Varicella may have a serious and sometimes fatal course, especially
      in immunocompromised patients. Some patient groups may need prophylaxis after
      exposure to the varicella-zoster-virus. In this article we review the evidence
      for usefulness of prophylactic measures after such exposure. MATERIAL AND
      METHODS: The article is based on a non-systematic literature search in Medline,
      the Cochrane Library, UpToDate and Clinical Evidence. RESULTS: The effect of post
      exposure varicella prophylaxis on disease rate and severity of varicella is only
      weakly documented. There is some evidence that passive immunisation with
      varicella-zoster immunoglobulin (VZIG) reduces the risk of serious disease when
      it is administered within 72-96 hours after exposure. Several studies of mostly
      healthy children have shown that prophylactic acyclovir is better than control
      treatment, but the studies are small and they are not properly designed. Post
      exposure vaccination is shown to reduce disease rate and severity in otherwise
      healthy children. INTERPRETATION: We believe that acyclovir or valacyclovir can
      be used as post-exposure varicella prophylaxis in risk patients for whom the time
      window for VZIG-use has expired.

PMID- 21901037
TI  - [Use of GnRH antagonist for in vitro fertilization].
AB  - BACKGROUND: For many patients, the typical treatment protocol for in vitro
      fertilization (IVF) is both physically and psychologically demanding. An
      alternative approach to use of gonadotropin-releasing hormone (GnRH)-agonists
      traditionally used to prevent premature ovulation, is use of GnRH-antagonists.
      The aim of this article is to describe advantages and disadvantages of using GnRH
      antagonists in IVF. MATERIAL AND METHODS: The paper is based on literature
      identified through a non-systematic search in PubMed, and more than ten years of
      clinical experience with use of GnRH antagonists in IVF. RESULTS: To maintain a
      similar pregnancy rate as that with GnRH-agonists, one can use GnRH-antagonists
      at an earlier time-point during stimulation of the ovaries and a lower dose of
      follicle stimulating hormone (FSH). A less intensive stimulation implies a lower
      risk of complications and side effects and a shorter treatment period before egg
      collection (from four-five weeks to less than two weeks). The main disadvantage
      of the GnRH-antagonist protocol is that ovarian stimulation cannot be programmed
      to the same extent as that with use of a GnRH-agonist. INTERPRETATION:
      Stimulation with a GnRH-antagonist instead of a GnRH-agonist in IVF, is less
      physically and psychologically demanding for the patients and maintains the same
      birth rate.

PMID- 21901038
TI  - [One-and-a-half syndrome].

PMID- 21901039
TI  - [A man in his 60s with severe respiratory failure].

PMID- 21901040
TI  - [Liver transplantation instead of lung transplantation].

PMID- 21901042
TI  - The global health architecture--for the benefit of all?

PMID- 21901043
TI  - A functioning health system is a prerequisite for good health care.

PMID- 21901044
TI  - Priorities in global health.

PMID- 21901045
TI  - Climate change--the biggest health threat of our time.

PMID- 21901046
TI  - [Difficult for Palestinians to receive specialist treatment].

PMID- 21901047
TI  - [Ethical aspects of physician-patient relations in the new media].

PMID- 21901050
TI  - Electric control of magnon frequencies and magnetic moment of bismuth ferrite
      thin films at room temperature.
AB  - Here, we report the tuning of room-temperature magnon frequencies from 473 GHz to
      402 GHz (14%) and magnetic moment from 4 to 18 emu/cm(3) at 100 Oe under the
      application of external electric fields (E) across interdigital electrodes in
      BiFeO(3) (BFO) thin films. A decrease in magnon frequencies and increase in
      phonon frequencies were observed with Magnon and phonon Raman intensities are
      asymmetric with polarity, decreasing with positive E (+E) and increasing with
      negative E (-E) where polarity is with respect to in-plane polarization P. The
      magnetoelectric coupling (alpha) is proved to be linear and a rather isotropic
      alpha = 8.5 * 10(-12) sm(-1).

PMID- 21901051
TI  - Transport of a soft cargo on a nanoscale ratchet.
AB  - Surface ratchets can guide droplet transport for microfluidic systems. Here, we
      demonstrated the actuation of microgels encapsulated in droplets using a
      unidirectional nanotextured surface, which moves droplets with low vibration
      amplitudes by a ratcheting mechanism. The nanofilm carries droplets along the
      ratchets with minimal drop shape deformation to move the encapsulated soft cargo,
      i.e., microscale hydrogels. The tilted nanorods of the nanofilm produce
      unidirectional wetting, thereby enabling droplet motion in a single direction.
      Maximum droplet translation speed on the nanofilm was determined to be 3.5 mm/s,
      which offers a pathway towards high throughput microgel assembly applications to
      build complex constructs.

PMID- 21901052
TI  - Neurogenesis and Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a neurodegenerative disease, characterized in the
      brain by amyloid plaque deposits and neurofibrillary tangles. It is the most
      common form of dementia among older people. There is at present no cure for AD,
      and current treatments consist mainly in drug therapy. Potential therapies for AD
      involve gene and cellular therapy. The recent confirmation that neurogenesis
      occurs in the adult brain and neural stem cells (NSCs) reside in the adult
      central nervous system (CNS) provide new opportunities for cellular therapy in
      the CNS, particularly for AD, and to better understand brain physiopathology.
      Hence, researchers have aimed at characterizing neurogenesis in patients with AD.
      Studies show that neurogenesis is increased in these patients, and in animal
      models of AD. The effect of drugs used to treat AD on neurogenesis is currently
      being investigated, to identify whether neurogenesis contributes to their
      therapeutic activities.

PMID- 21901053
TI  - Inhibition of intrinsic thrombin generation.
AB  - BACKGROUND: The contact phase of coagulation is of physiologic/pathophysiologic
      importance, whenever unphysiologic polynegative substances such as cell fragments
      (microparticles) get in contact with blood. There are several clinically used
      inhibitors of intrinsic thrombin generation. Here the inhibitory concentrations
      50% (IC50) of these anticoagulants are measured by the highly specific thrombin
      generation assay INCA. METHODS: Unfrozen pooled normal citrated plasma in
      polystyrole tubes was supplemented at 23 degrees C in duplicate with 0-2 IU/ml
      low molecular weight heparin (dalteparin), 0-2 IU/ml unfractionated heparin, 0
      500 KIU/ml aprotinin, or 0-40 mM arginine. 50 MUl plasma or 1 IU/ml thrombin
      standard were pipetted into a polystyrole microtiter plate with flat bottom. 5
      MUl SiO(2)/CaCl(2) - reagent (INCA activator) were added and after 0-30 min
      incubation at 37 degrees C 100 MUl 2.5 M arginine, pH 8.6, were added; arginine
      inhibits hemostasis activation and depolymerizes generated fibrin within 20 min
      at 23 degrees C. The in the physiologic 37 degrees C incubation phase generated
      thrombin was then chromogenically detected. The intra-assay CV values were < 5%.
      RESULTS AND DISCUSSION: The approximate IC50 were 0.01 IU/ml dalteparin, 0.02
      IU/ml heparin, 25 KIU/ml aprotinin, and 12 mM arginine. The efficiency of any
      anticoagulant on intrinsic thrombin generation should be measured for each
      individual patient.

PMID- 21901054
TI  - Neurogenesis and the effect of antidepressants.
AB  - The recent evidence that neurogenesis occurs throughout adulthood and neural stem
      cells (NSCs) reside in the adult central nervous system (CNS) suggests that the
      CNS has the potential for self-repair. Beside this potential, the function of
      newly generated neuronal cells in the adult brain remains the focus of intense
      research. The hippocampus of patients with depression show signs of atrophy and
      neuronal loss. This suggests that adult neurogenesis may contribute to the
      biology of depression. The observations that antidepressants, like fluoxetine,
      increase neurogenesis in the dentate gyrus (DG) and neurogenesis is required for
      the behavioral effect of antidepressants, lead to a new theory for depression and
      the design of new strategies and drugs for the treatment of depression. However,
      the role of adult neurogenesis in the etiology of depression remains the source
      of controversies and debates.

PMID- 21901056
TI  - The Way that PEGyl-DSPC Liposomal Doxorubicin Particles Penetrate into Solid
      Tumor Tissue.
AB  - BACKGROUND: For enhancement of drug effectiveness and reduction of drug toxicity,
      liposomal drugs have been studied in laboratories and clinics for decades.
      Although the results obtained from in vitro are encouraging, but the results from
      in vivo tests were not satisfactory. The main reasons for this situation were
      that we do not have enough information about the way how liposomal particles
      penetrating into solid tumor tissue, and what happening to the liposome particles
      after they got into the tumor tissue. In this paper, we are going to report the
      results from our observations on the way folic acid targeted and non-targeted
      PEGyl-DSPC liposomal doxorubicin particles penetrate into solid tumor tissue.
      METHODS: Subcutaneous transplanted murine L1210JF solid tumors in mice were used
      as a model. PEGyl liposomal doxorubicins were injected through tail venue, and
      tumor tissue samples were collected at special time points. Cryosections were cut
      and dried by a flowing of air after mounted on the slides right away. Then the
      dried cryosections were stained in water systems; the blood vessel cells were
      stained with green fluorescent FITC labeled antibody against CD31 antigen; the
      nuclei of the living cells were stained with a blue fluorescent dye DAPI. Since
      the whole procedure was carried out in aquatic system, the red color fluorescent
      liposomal doxorubicin particles remain visible under fluorescence microscope.
      RESULTS: Both folate conjugated and non-conjugated PEGyl-DSPC liposomal
      doxorubicin particles were only leaking out from the broken holes of blood
      vessels with a special direction and spread out for a limited distance, which was
      similar to the results showed before, in that observation a latex microsphere
      sample was used as a model.

PMID- 21901055
TI  - Modification of Monoaminergic Activity by MAO Inhibitors Influences
      Methamphetamine Actions.
AB  - Methamphetamine (METH) abuse is a serious health and social problem worldwide. At
      present, however, there are no effective medications for the treatment of METH
      abuse. Of the intracellular METH target proteins, monoamine oxidase (MAO) is
      involved in the regulation of monoaminergic tone in the brain, resulting in the
      modulation of METH-induced behavioral abnormalities in mammals. The METH-induced
      expression of increased motor activity, stereotypy, and sensitization is closely
      associated with monoaminergic transmission in the brain. Modification of MAO
      activity by MAO inhibitors can influence METH action. Of the MAO inhibitors, the
      propargylamine derivative clorgyline, an irreversible MAO-A inhibitor,
      effectively blocks METH-induced hyperlocomotion and behavioral sensitization in
      rodents. Analysis of the associated monoaminergic activity indicates an
      involvement of altered striatal serotonergic transmission as well as an increased
      dopaminergic tone. Some effects of MAO inhibitors on METH action appear to be
      independent of MAO, suggesting complex mechanisms of action of MAO inhibitors in
      METH abuse. This review describes current research to find effective treatment
      for METH abuse, using MAO inhibitors.

PMID- 21901057
TI  - Long-term L-carnitine administration reduces erythropoietin resistance in chronic
      hemodialysis patients with thalassemia minor.
AB  - BACKGROUND AND AIM: Both thalassemia and carnitine deficiency represent
      independent causes of erythropoietin resistance, and thus anemia, in uremic
      patients. We evaluated the unknown long-term effects of L-carnitine
      administration in beta-thalassemic on chronic hemodialysis. METHODS: We studied
      twelve subjects (M = 8; F = 4) affected by beta-thalassemia minor (beta-thal;
      HbA2 level = 6.6 +/- 0.6%) and forty non-thalassemic subjects (M = 24; F = 16) as
      controls (C), on chronic hemodialysis treatment. Patients and controls were at
      target hemoglobin levels (11-12g/dl) prior to the study and underwent to i.v. L
      carnitine administration for a one year period-time. RESULTS: Groups were
      comparable for age, gender, serum levels of hemoglobin (Hb), iron, ferritine, PTH
      and aluminum, transferrin saturation, and dialysis modalities. During the study
      both groups showed significant Hb increase and erythropoietin (EPO) decrease; as
      a difference, such changes emerged at the 3rd month in C but at the 8th month in
      beta-thal. At start, during the dialysis session the erythrocyte MCV reduced in C
      but not in beta-thal (65.3 +/- 3.2 to 65.5 +/- 3.2 fl; NS); along carnitine
      administration period, however, MCV during dialysis decreased also in beta-thal,
      starting since the 9th month of treatment. CONCLUSION: This study provides
      evidence of the lowering of EPO resistance in beta-thalassemia patients on
      hemodialysis due to long-term carnitine administration. Thus, prolonged carnitine
      supplementation should be suggested to patients on dialysis affected by beta
      thalassemia with poorly responsive anemia, or requiring large doses of
      erythropoietin.

PMID- 21901058
TI  - Cyclophilin and viruses: cyclophilin as a cofactor for viral infection and
      possible anti-viral target.
AB  - Cyclophilin (CyP) is a peptidyl prolyl cis/trans isomerase, catalyzing the cis
      trans isomerization of proline residues in proteins. CyP plays key roles in
      several different aspects of cellular physiology including the immune response,
      transcription, mitochondrial function, cell death, and chemotaxis. In addition to
      these cellular events, a number of reports demonstrated that CyP plays a critical
      role in the life cycle of viruses, especially human immunodeficiency virus (HIV)
      and hepatitis C virus (HCV). These two viruses are significant causes of
      morbidity and mortality worldwide, but current therapies are often insufficient.
      CyP may provide a novel therapeutic target for the management and/or cure of
      these diseases, in particular HCV.

PMID- 21901059
TI  - Effect of ribavirin alone or combined with silymarin on carbon tetrachloride
      induced hepatic damage in rats.
AB  - The effect of the antiviral agent ribavirin given alone or in combination with
      silymarin on the development of liver injury induced in rats with carbon
      tetrachloride (CCl(4); 2.8 ml/kg followed by 1.4 ml/kg after one week) was
      studied. Ribavirin at three dose levels (30, 60 or 90 mg/kg), silymarin (25
      mg/kg) or combination of ribavirin (60 mg/kg) and silymarin (25 mg/kg) was
      administered once daily orally for 14 days, starting at time of administration of
      CCl(4). The administration of ribavirin decreased the elevations in serum alanine
      aminotransferase (ALT) by 78.5, 82.1, 75.1%, aspartate aminotransferase (AST)
      47.5, 37.4, 38.8%, and alkaline phosphatase (ALP) by 23.4, 16, 21.6%,
      respectively and also pre-vented the development of hepatic necrosis caused by
      CCl(4). In comparison, the elevated serum ALT, AST and ALP levels decreased to
      43.3%, 46%, and 37.5% of controls, respectively by silymarin. When silymarin was
      combined with ribavirin, the serum activities of AST and ALP were further
      decreased, indicating a beneficial additive effect. Morphometric analysis
      indicated significant reduction in the area of necrosis and fibrosis on ribavirin
      treatment and this was further reduced after the addition of silymarin. Metabolic
      pertuberations caused by CCl(4) as reflected in a decrease in intracellular
      protein content in hepatocytes were improved by ribavirin monotherapy and to
      higher extent by combined silymarin and ribavirin therapy. Proliferating cell
      nuclear antigen was reduced in nuclei of hepatocytes by ribavirin montherapy or
      the combination of ribavirin and silymarin compared with CCl(4)-control group.
      The study demonstrates that ribavirin treatment in the model of CCl(4)-induced
      liver injury results in less liver damage. Results also indicate that the
      combined application of ribavirin and sily-marin is likely to be a useful
      additive in reducing liver injury.

PMID- 21901060
TI  - Modulation of visceral nociception, inflammation and gastric mucosal injury by
      cinnarizine.
AB  - The effect of cinnarizine, a drug used for the treatment of vertigo was assessed
      in animal models of visceral nociception, inflammation and gastric mucosal
      injury. Cinnarizine (1.25-20 mg/kg, s.c.) caused dose-dependent inhibition of the
      abdominal constrictions evoked by i.p. injection of acetic acid by 38.7-99.4%.
      This effect of cinnarizine (2.5 mg/kg) was unaffected by co-administration of the
      centrally acting dopamine D2 receptor antagonists, sulpiride, haloperidol or
      metoclopramide, the peripherally acting D2 receptor antagonist domperidone, but
      increased by the D2 receptor agonist bromocryptine and by the non-selective
      dopamine receptor antagonist chlorpromazine. The antinociception caused by
      cinnarizine was naloxone insenstive, but enhanced by propranolol, atropine and by
      yohimbine. The antinociceptive effect of cinnarizine was prevented by co
      treatment with the adenosine receptor blocker theophylline or by the ATP
      sensitive potassium channel (K(ATP)) blocker glibenclamide. Cinnarizine at 2.5
      mg/kg reversed the baclofen-induced antinociception. Cinnarizine at 2.5 mg/kg
      reduced immobility time in the Porsolt's forced-swimming test by 24%. Cinnarizine
      inhibited the paw oedema response to carrageenan and reduced gastric mucosal
      lesions caused by indomethacin in rats. It is suggested that cinnarizine exerts
      anti-inflammatory, antinociceptive and gastric protective properties. The
      mechanism by which cinnarizine modulates pain transmission is likely to involve
      adenosine receptors and K(ATP) channels.

PMID- 21901061
TI  - The adaptogens rhodiola and schizandra modify the response to immobilization
      stress in rabbits by suppressing the increase of phosphorylated stress-activated
      protein kinase, nitric oxide and cortisol.
AB  - Adaptogens possess anti-fatigue and anti-stress activities that can increase
      mental and physical working performance against a background of fatigue or
      stress. The aim of the present study was to ascertain which mediators of stress
      response are significantly involved in the mechanisms of action of adaptogens,
      and to determine their relevance as biochemical markers for evaluating anti
      stress effects in rabbits subjected to restraint stress. Blood levels of stress
      activated protein kinase (SAPK/JNK), the phosphorylated kinase p-SAPK/p-JNK,
      nitric oxide (NO), cortisol, testosterone, prostaglandin E(2), leukotriene B(4)
      and thromboxane B(2) were determined in groups of animals prior to daily oral
      administration of placebo, rhodioloside or extracts of Eleutherococcus
      senticosus, Schizandra chinensis, Rhodiola rosea, Bryonia alba and Panax ginseng
      over a 7 day period. Ten minutes after the final treatment, animals were
      immobilized for 2 hours and blood levels of the markers re-determined. In the
      placebo group, only p-SAPK/p-JNK, NO and cortisol were increased significantly
      (by 200-300% cf basal levels) following restraint stress, whilst in animals that
      had received multiple doses of adaptogens/stress-protectors, the levels of NO and
      cortisol remained practically unchanged after acute stress. Rhodioloside and
      extracts of S. chinensis and R. rosea were the most active inhibitors of stress
      induced p-SAPK/p-JNK. E. senticosus, B. alba and P. ginseng exerted little effect
      on p-SAPK/p-JNK levels. It is suggested that the inhibitory effects of R. rosea
      and S. chinensis on p-SAPK/p-JNK activation may be associated with their
      antidepressant activity as well as their positive effects on mental performance
      under stress.

PMID- 21901062
TI  - Accelerators of osteogenesis by recombinant human bone morphogenetic protein-2.
AB  - Bone morphogenetic protein (BMP) appears to be one of the most promising cytokine
      and for clinical use in reconstructive surgery for bony defects and augmentation.
      To evaluate the effect of basic fibroblast growth factor (bFGF), FK506,
      elcatonin, and hyperbaric oxygenation (HBO) on osteoinduction by recombinant
      human bone morphogenetic protein-2 (rhBMP-2), 2 or 5 MUg of rhBMP-2 was implanted
      into intramuscular sites of rats. At 21 days after implantation, the
      osteoinductive activity in the treatment group and control group was compared
      radiographically, biochemically, and histologically. The amount of new bone in
      the treatment group was significantly greater than that in the control group. The
      alkaline phosphatase activity and calcium content in the treatment group were
      significantly higher than those in the control group. These results suggest that
      bFGF, FK506, elcatonin, and HBO accelerated the activity and rate of
      osteoinduction by rhBMP2. These results may be useful when BMP is applied
      clinically in near future.

PMID- 21901063
TI  - Electrocardiographic findings in acutely and chronically T. cruzi-infected mice
      treated by a phenyl-substituted analogue of furamidine DB569.
AB  - Aromatic diamidines have been successfully used to combat a wide range of
      parasites that cause important human infections. Recently we reported that a N
      phenyl-substituted analogue of furamidine (DB569) exerts a micromolar
      trypanocidal activity against Trypanosoma cruzi in vitro. Since DB569 also
      reduces the cardiac parasitism and increases the survival rates of T. cruzi
      infected mice, our present aim was to analyze the potential protection of DB569
      in the development of altered cardiac electrical conduction system during acute
      and chronic T. cruzi infection. In our experimental model of acute infection
      (Swiss mice inoculated with Y strain of T. cruzi), the prevailing disorder
      observed in electrocardiogram (ECG) analyses was sinus bradycardia. This ECG
      alteration was reverted in acutely infected mice treated with DB569.
      Interestingly, the DB569 treatment reduced significantly the numbers of CD8(+) T
      cells in the cardiac infiltration. In addition, the noticed protection of DB569
      in the ECG findings of acutely-infected animals was further extended to the
      chronic infection. Our data suggest that the reversion to and further maintenance
      of normal ECG profile in the DB569-treated infected animals may be associated
      with the reduced cardiac CD8(+) lymphocyte infiltration and parasitism that might
      be ultimately contributing to their increased survival rates.

PMID- 21901064
TI  - Targeting receptors, transporters and site of absorption to improve oral drug
      delivery.
AB  - Although the oral route of drug administration is the most acceptable way of self
      medication with a high degree of patient compliance, the intestinal absorption of
      many drugs is severely hampered by different biological barriers. These barriers
      comprise of biochemical and physical components. The biochemical barrier includes
      enzymatic degradation in the gastrointestinal lumen, brush border and in the
      cytoplasm of the epithelial cells as well as efflux transporters that pump drug
      molecules from inside the epithelial cell back to the gastrointestinal lumen. The
      physical barrier consists of the epithelial cell membranes, tight junctions and
      mucus layer. Different strategies have been applied to improve the absorption of
      drugs after oral administration, which range from chemical modification of drug
      molecules and formulation technologies to the targeting of receptors,
      transporters and specialized cells such as the gut-associated lymphoid tissues.
      This review focuses specifically on the targeting of receptor-mediated
      endocytosis, transporters and the absorption-site as methods of optimizing
      intestinal drug absorption. Intestinal epithelial cells express several nutrient
      transporters that can be targeted by modifying the drug molecule in such a way
      that it is recognized as a substrate. Receptor-mediated endocytosis is a
      transport mechanism that can be targeted for instance by linking a receptor
      substrate to the drug molecule of interest. Many formulation strategies exist for
      enhancing drug absorption of which one is to deliver drugs at a specific site in
      the gastrointestinal tract where optimum drug absorption takes place.

PMID- 21901065
TI  - Phospholipase A(2) activates hemostasis.
AB  - BACKGROUND: Phospholipases A(2) (PLA(2)) are aggressive enzymes that can destroy
      phospholipids of cell membranes. The resulting cell fragments trigger the
      kallikrein-mediated contact phase of coagulation. The aim of the present study
      was to expose citrated whole blood to PLA(2) and to quantify thrombin generation
      in recalcified plasma. METHODS: Normal citrated blood was exposed to bovine
      pancreatic or snake PLA(2), lipopolysaccharide (LPS), or zymosan A for 30-45 min
      (RT). After centrifugation the plasma samples were recalcified (10 + 1) with 250
      mM CaCl(2) in the recalcified coagulation activity assay (RECA). After 0-45 min
      coagulation reaction time (CRT at 37 degrees C) 1.6 M arginine (final test
      concentration) was added to stop hemostasis activation and to depolymerize non
      crosslinked fibrin. The generated thrombin activity was chromogenically
      determined. RESULTS: 100 ng/ml bovine pancreatic or snake PLA(2) generates about
      0.2-0.8 IU/ml thrombin after 15 min CRT. This thrombin generation is similar as
      that induced by 200 ng/ml LPS or 20 MUg/ml zymosan A. Up to 60 ng/ml bovine
      pancreatic PLA(2) the generated thrombin activity is proportional to the PLA(2)
      activity used; 1 MUg/ml PLA(2) induces much less thrombin, but PLA(2) at 10
      MUg/ml again results into thrombin generation of 0.1-3 IU/ml at 10-15 min CRT. As
      control, in pooled normal citrated plasma there is no significant change in
      thrombin generation when exposed to up to 10 MUg/ml bovine pancreatic PLA(2).
      DISCUSSION: Elevated plasmatic PLA(2) activities (occurring e.g. in trauma,
      pancreatitis, or sepsis) activate the blood hemostasis system resulting in
      pathologic disseminated intravascular coagulation (PDIC). It is suggested to
      diagnose these life threatening states as early as possible, screening all
      patients for plasmatic thrombin activity.

PMID- 21901066
TI  - Cardiovascular pharmacology of sinomenine: the mechanical and
      electropharmacological actions.
AB  - Sinomenine is one of the alkaloids extracted from Chinese medical plant,
      Sinomenium acutum Rehder et Wilson. Sinomenine has been used for Rheumatoid
      arthritis as an anti-inflammatory and immunomodulative drugs. We have so far been
      investigated the cardiovascular pharmacological actions of sinomenine. Sinomenine
      dilated NE (5 MUM)-, KCl (60 mM)- and PDB (300 nM)-induced vasoconstrictions. The
      pretreatment with nicardipine (0.1 MUM), staurosporine (30 nM), L-NMMA (100 MUM),
      indomethacin (10 MUM) or propranolol significantly attenuated the sinomenine
      induced vasorelaxation. Therefore, these results indicate that sinomenine causes
      the vasorelaxation by the involvement with the inhibitions of Ca(2+) current
      (I(Ca)) and PK-C, beta-adrenoceptor stimulation, and the activation of NO and
      PGI(2) syntheses in endothelium. On the other hand, in the ventricular
      cardiomyocytes of guinea pig, sinomenine inhibits I(Ca) and simultaneously
      decreases the delayed rectifier K(+) current (I(K)), resulting in the
      prolongation of action potential duration. Sinomenine also suppresses the
      dysrhysmias induced by triggered activities under the Ca(2+) overload condition.
      Therefore, sinomenine may be expected as one of effective therapeutic drugs for
      heart failure and dysrhythmias, and may maintain the cardiovascular functions due
      to modulation of cardiac ionic channels and blood vessels.

PMID- 21901067
TI  - Circulating vascular endothelial growth factor (VEGF) levels in advanced stage
      cancer patients compared to normal controls and diabetes mellitus patients with
      critical ischemia.
AB  - Anti-angiogenic therapy is emerging as a valuable tool in the treatment of
      patients with cancer. As VEGF is a central target in anti-angiogenic therapy, its
      levels in the circulation might be relevant in selecting tumor types or patients
      likely to respond to this treatment. Additional VEGF has been recognized as a key
      factor in the pathogenesis of diabetic retinopathy. Recently anti-angiogenic
      therapy has been advocated in this situation.We measured VEGF levels in whole
      blood in 42 patients with high grade (n = 26) and low grade (n = 16) end stage
      cancer, and in 28 healthy controls and 37 patients with diabetes related vascular
      disease. Only 2/26 patients in the group of high grade cancer had significantly
      elevated VEGF levels, 1/16 in the low grade group and 1/28 in the healthy control
      group. In contrast, in 10/37 diabetic patients the mean VEGF levels were
      significantly elevated compared to the other groups. The mean level in these
      diabetic patients was significantly elevated compared to the other groups.These
      data indicate the limitation of the use of circulating VEGF levels as a potential
      selection criterion for anti-angiogenic therapy in cancer patients and suggest
      further studies into its application in the management of diabetic complications.

PMID- 21901068
TI  - Endothelial dysfunction, erectile dysfunction and phosphodiesterase 5 inhibitors.
      An update of the current data and future perspectives.
AB  - Endothelial dysfunction is a pathological entity that multiply affects the health
      status. Erectile dysfunction is being recognized as a condition that is strongly
      interrelated with endothelial dysfunction, being a vascular event itself. Oral
      pharmacotherapy for erectile dysfunction has provided us with a new armamentarium
      on this condition. Phosphodiesterase 5 inhibitors have been investigated and
      proved useful in clinical practice for erectile dysfunction but in addition to
      this, the results seem promising of a beneficial effect on endothelial
      dysfunction, as well.

PMID- 21901069
TI  - The relationship of arginine deprivation, argininosuccinate synthetase and cell
      death in melanoma.
AB  - It has been shown that melanoma cells do not express argininosuccinate synthetase
      (ASS) and therefore are unable to synthesize arginine from citrulline. Depleting
      arginine using pegylated arginine deiminase (ADI-PEG20) results in cell death in
      melanoma but not normal cells. This concept was translated into clinical trial
      and responses were seen. However, induction of ASS expression does occur which
      results in resistance to ADI-PEG20. We have used 4 melanoma cell lines to study
      factors which may govern ASS expression. Although these 4 melanoma cell lines do
      not express ASS protein or mRNA as detected by both immunoblot and northernblot
      analysis, ASS protein can be induced after these cells are grown in the presence
      of ADI-PEG20, but again repressed after replenishing arginine in the media. The
      levels of induction are different and one cell line could not be induced.
      Interestingly, a melanoma cell line with the highest level of induction could
      also be made resistant to ADI-PEG20. This resistant line possesses high levels of
      ASS mRNA and protein expression which cannot be repressed with arginine. Our
      study indicates that ASS expression in melanoma cells is complex and governed by
      biochemical parameters which are different among melanoma cells.

PMID- 21901070
TI  - Trypanothione reductase: a viable chemotherapeutic target for antitrypanosomal
      and antileishmanial drug design.
AB  - Trypanosomiasis and leishmaniasis are two debilitating disease groups caused by
      parasites of Trypanosoma and Leishmania spp. and affecting millions of people
      worldwide. A brief outline of the potential targets for rational drug design
      against these diseases are presented, with an emphasis placed on the enzyme
      trypanothione reductase. Trypanothione reductase was identified as unique to
      parasites and proposed to be an effective target against trypanosomiasis and
      leishmaniasis. The biochemical basis of selecting this enzyme as a target, with
      reference to the simile and contrast to human analogous enzyme glutathione
      reductase, and the structural aspects of its active site are presented. The
      process of designing selective inhibitors for the enzyme trypanothione reductase
      has been discussed. An overview of the different chemical classes of inhibitors
      of trypanothione reductase with their inhibitory activities against the parasites
      and their prospects as future chemotherapeutic agents are briefly revealed.

PMID- 21901071
TI  - Polymeric nanoparticles, nanospheres and nanocapsules, for cutaneous
      applications.
AB  - This review presents an overview about pharmaceutical and cosmetic topical
      products containing polymeric nanoparticles (nanospheres and nanocapsules),
      reporting the main preparation and characterization methods and the studies of
      penetration and transport of substances through the skin. The penetration and
      transport extent of those systems through the skin depends on the ingredients
      chemical composition, on the encapsulation mechanism influencing the drug
      release, on the size of nanoparticles and on the viscosity of the formulations.
      The polymeric nanoparticles are able to modify the activity of drugs, delay and
      control the drug release, and increase the drug adhesivity or its time of
      permanence in the skin. Briefly, the nanoparticles can be useful as reservoirs of
      lipophilic drugs to deliver them in the stratum corneum becoming an important
      strategy to control their permeation into the skin.

PMID- 21901073
TI  - Delivery systems for in vivo use of nucleic Acid drugs.
AB  - The notorious biotechnological advance of the last few decades has allowed the
      development of experimental methods for understanding molecular mechanisms of
      genes and new therapeutic approaches. Gene therapy is maturing into a viable,
      practical method with the potential to cure a variety of human illnesses. Some
      nucleic-acid-based drugs are now available for controlling the progression of
      genetic diseases by inhibiting gene expression or the activity of their gene
      products. New therapeutic strategies employ a wide range of molecular tools such
      as bacterial plasmids containing transgenic inserts, RNA interference and
      aptamers. A nucleic-acid based constitution confers a lower immunogenic potential
      and as result of the high stringency selection of large molecular variety, these
      drugs have high affinity and selectivity for their targets. However, nucleic
      acids have poor biostability thus requiring chemical modifications and delivery
      systems to maintain their activity and ease their cellular internalization. This
      review discusses some of the mechanisms of action and the application of
      therapies based on nucleic acids such as aptamers and RNA interference as well as
      platforms for cellular uptake and intracellular delivery of therapeutic
      oligonucleotides and their trade-offs.

PMID- 21901075
TI  - Use and safety of anthroposophic medications for acute respiratory and ear
      infections: a prospective cohort study.
AB  - OBJECTIVE: Anthroposophic medications (AMED) are widely used, but safety data on
      AMED from large prospective studies are sparse. The objective of this analysis
      was to determine the frequency of adverse drug reactions (ADR) to AMED in
      outpatients using AMED for acute respiratory and ear infections. METHODS: A
      prospective four-week observational cohort study was conducted in 21 primary care
      practices in Europe and the U.S.A. The cohort comprised 715 consecutive
      outpatients aged >=1 month, treated by anthroposophic physicians for acute otitis
      and respiratory infections. Physicians' prescription data and patient reports of
      adverse events were analyzed. Main outcome measures were use of AMED and ADR to
      AMED. RESULTS: two patients had confirmed ADR to AMED: 1) swelling and redness at
      the injection site after subcutaneous injections of Prunus spinosa 5%, 2)
      sleeplessness after intake of Pneumodoron((r)) 2 liquid. These ADR lasted one and
      two days respectively; both subsided after dose reduction; none were unexpected;
      none were serious. The frequency of confirmed ADR to AMED was 0.61% (2/327) of
      all different AMED used, 0.28% (2/715) of patients, and 0.004% (3/73,443) of
      applications. CONCLUSION: In this prospective study, anthroposophic medications
      used by primary care patients with acute respiratory or ear infections were well
      tolerated.

PMID- 21901074
TI  - Targeted brain tumor treatment-current perspectives.
AB  - Brain tumor is associated with poor prognosis. The treatment option is severely
      limited for a patient with brain tumor, despite great advances in understanding
      the etiology and molecular biology of brain tumors that have lead to
      breakthroughs in developing pharmaceutical strategies, and ongoing NCI/Pharma
      sponsored clinical trials. We reviewed the literature on molecular targeted
      agents in preclinical and clinical studies in brain tumor for the past decade,
      and observed that the molecular targeting in brain tumors is complex. This is
      because no single gene or protein can be affected by single molecular agent,
      requiring the use of combination molecular therapy with cytotoxic agents. In this
      review, we briefly discuss the potential molecular targets, and the challenges of
      targeted brain tumor treatment. For example, glial tumors are associated with
      over-expression of calcium-dependent potassium (K(Ca)) channels, and high grade
      glioma express specific K(Ca) channel gene (gBK) splice variants, and mutant
      epidermal growth factor receptors (EGFRvIII). These specific genes are promising
      targets for molecular targeted treatment in brain tumors. In addition, drugs like
      Avastin and Gleevec target the molecular targets such as vascular endothelial
      cell growth factor receptor, platelet-derived growth factor receptors, and BRC
      ABL/Akt. Recent discovery of non-coding RNA, specifically microRNAs could be used
      as potential targeted drugs. Finally, we discuss the role of anti-cancer drug
      delivery to brain tumors by breaching the blood-brain tumor barrier. This non
      invasive strategy is particularly useful as novel molecules and humanized
      monoclonal antibodies that target receptor tyrosine kinase receptors are rapidly
      being developed.

PMID- 21901072
TI  - Targeting human immunodeficiency virus type 1 assembly, maturation and budding.
AB  - The targets for licensed drugs used for the treatment of human immunodeficiency
      virus type 1 (HIV-1) are confined to the viral reverse transcriptase (RT),
      protease (PR), and the gp41 transmembrane protein (TM). While currently approved
      drugs are effective in controlling HIV-1 infections, new drug targets and agents
      are needed due to the eventual emergence of drug resistant strains and drug
      toxicity. Our increased understanding of the virus life-cycle and how the virus
      interacts with the host cell has unveiled novel mechanisms for blocking HIV-1
      replication. This review focuses on inhibitors that target the late stages of
      virus replication including the synthesis and trafficking of the viral
      polyproteins, viral assembly, maturation and budding. Novel approaches to
      blocking the oligomerization of viral enzymes and the interactions between viral
      proteins and host cell factors, including their feasibility as drug targets, are
      discussed.

PMID- 21901076
TI  - Effect of live Salmonella Ty21a in dextran sulfate sodium-induced colitis.
AB  - BACKGROUND: Intestinal microbiota seems to play an essential role in the
      development of inflammatory bowel diseases (IBD). We hypothesised that an oral
      vaccine based on live Salmonella typhi would be well tolerated and could even
      attenuate dextran sulfate sodium (DSS) induced colitis in rats, an animal model
      of IBD. METHODS: Nine male Wistar rats was used for an initial tolerance study,
      in which we used 3 dose-levels of Salmonella Ty21a, 0.5 * 10(9), 1 * 10(9), and 2
      * 10(9)CFU, each dose being tested in 3 rats. Four treatment groups consisting of
      8 male Wistar rats per group: 1) control group given standard food and water, 2)
      control group given four daily administrations of Salmonella Ty21a 1 * 10(9) CFU,
      3) water with 5% DSS the last 7 days, 4) four daily administrations of Salmonella
      Ty21a before water with 5% DSS the last 7 days. The Salmonella Ty21a was
      administered by gastric gavage on day 1, 3, 5 and 16, while DSS was given with
      the drinking water from day 15 to 22. The animals were sacrificed and colonic
      tissue removed for analysis 22 days after gavage of the first vaccine dose.
      RESULTS: The animals in the tolerance study got no signs of disease. In the
      treatment study, all animals receiving DSS had histologic indications of colitis,
      particularly in the distal part of the colon. Administration of Salmonella Ty21a
      had no significant effect on crypt and inflammation scores (p > 0.05).
      CONCLUSION: Gastric administration of live vaccine strain Salmonella Ty21a was
      well tolerated, but did not provide any significant protection against
      development of DSS induced colitis in rats.

PMID- 21901078
TI  - Platelet-derived growth factor as a therapeutic target for systemic autoimmune
      diseases.
AB  - Some systemic rheumatic diseases and disorders, especially fibrotic and vascular
      disorders, are often refractory to corticosteroid therapy. Recently, ever
      accumulating evidence suggests that platelet-derived growth factor (PDGF) is
      involved in those refractory diseases. Imatinib mesylate inhibits the activation
      of PDGF receptor as well as c-Abl, Bcr-Abl and c-Kit tyrosine kinases. It has
      therefore been widely used for the treatment of chronic myeloid leukemia and
      gastrointestinal stromal tumors. Imatinib effectively suppresses the activation
      and proliferation of fibroblasts, mesangial cells and smooth muscle cells both in
      vitro and in vivo. Additionally, it has recently been reported that some patients
      with rheumatoid arthritis or idiopathic pulmonary arterial hypertension
      demonstrated a good clinical response to imatinib therapy. Imatinib may therefore
      overcome the limitations of current therapeutic strategy with corticosteroids and
      immunosuppressive agents for refractory diseases, such as systemic sclerosis and
      interstitial lung diseases, without clinical intolerability.

PMID- 21901077
TI  - New insights into the understanding of gastrointestinal dysmotility.
AB  - Our understanding of the physiology of digestion, absorption, secretion, and
      motility in the gastrointestinal tract has improved immensely. Today it is well
      established that the gross functions of the gastrointestinal tract depend on the
      coordination between the muscles, nerves and hormones. The enteric nervous system
      (ENS) is involved in most of the physiological and pathophysiological processes
      in the gastrointestinal tract. Therefore, clinical and experimental studies on
      the ENS provide the basis for a better understanding of the mechanisms involved
      in gastrointestinal disorders and promote the development of therapeutic options.
      This review outlines some of the current views on the role of the ENS and its
      related hormones in gastrointestinal motility.

PMID- 21901079
TI  - Effects of ascorbic Acid, alpha-tocopherol and allopurinol on ischemia
      reperfusion injury in rabbit skeletal muscle: an experimental study.
AB  - PURPOSE: Ischemia reperfusion injury to skeletal muscle, following an acute
      arterial occlusion is important cause of morbidity and mortality. The aim of the
      present study was to determine and evaluate the effects of ascorbic acide, alpha
      tocopherol and allopurinol on ischemia reperfusion injury in rabbit skeletal
      muscle. METHODS: Forty-eight New Zealand white rabbits, all male, weighing
      between 2.5 to 3.0 (mean 2.8) kg, were used in the study. They were separated
      into four groups. Group I was the control group without any drugs. The other
      groups were treatment groups (groups II, III, and IV). Group II rabbits
      administrated 50 mg/kg ascorbic acide and 100 mg/kg alpha-tocopherol 3 days prior
      to ischemia, group III rabbits received 50 mg/kg allopurinol 2 days prior to
      ischemia, and group IV rabbits were administrated both 50 mg/kg ascorbic acide,
      100 mg/kg alpha-tocopherol 3 days prior to ischemia and 50 mg/kg allopurinol 2
      days prior to ischemia. Two hours ischemia and 2 hours reperfusion were underwent
      to the treatment groups. At the end of the reperfusion periods, muscle samples
      were taken from rectus femoris muscle for determination of superoxide dismutase,
      catalase and glutathione peroxidase activities as antioxidant enzymes, and
      malondialdehyde as an indicator of lipid peroxidation and xanthine oxidase levels
      as source hydroxyl radical. Besides, histopathological changes (edema,
      inflammation, ring formation and splitting formation) were evaluated in the
      muscle specimens. RESULTS: In the treatment groups; superoxide dismutase
      (U/mgprotein), catalase (U/mgprotein), and glutathione peroxidase (U/mgprotein)
      levels increased, malondialdehyde (nmol/mgprotein) and xanthine oksidase
      (mU/mgprotein) levels decreased compared to control I ( p < 0.05). Increase of
      superoxide dismutase, catalase, and glutathione peroxidase levels were the
      highest and decrease of malondialdehyde and xanthine oxidase levels were the
      highest in group IV compared to groups II and III, but no significant as
      statistically. Also amount of cellular injury in group II, III, and IV were lower
      than group I. CONCLUSIONS: Antioxidant medication may help lowering ischemia
      reperfusion injury. In our study, all drug medications are shown to be able to
      have an effective role for preventing ischemia reperfusion injury. Moreover,
      ascorbic acide + alpha-tocopherol + allopurinol group (group IV) may have a
      beneficial effect to decrease the local and systemic damage due to ischemia
      reperfusion injury.

PMID- 21901081
TI  - Towards a system level understanding of non-model organisms sampled from the
      environment: a network biology approach.
AB  - The acquisition and analysis of datasets including multi-level omics and
      physiology from non-model species, sampled from field populations, is a
      formidable challenge, which so far has prevented the application of systems
      biology approaches. If successful, these could contribute enormously to improving
      our understanding of how populations of living organisms adapt to environmental
      stressors relating to, for example, pollution and climate. Here we describe the
      first application of a network inference approach integrating transcriptional,
      metabolic and phenotypic information representative of wild populations of the
      European flounder fish, sampled at seven estuarine locations in northern Europe
      with different degrees and profiles of chemical contaminants. We identified
      network modules, whose activity was predictive of environmental exposure and
      represented a link between molecular and morphometric indices. These sub-networks
      represented both known and candidate novel adverse outcome pathways
      representative of several aspects of human liver pathophysiology such as liver
      hyperplasia, fibrosis, and hepatocellular carcinoma. At the molecular level these
      pathways were linked to TNF alpha, TGF beta, PDGF, AGT and VEGF signalling. More
      generally, this pioneering study has important implications as it can be applied
      to model molecular mechanisms of compensatory adaptation to a wide range of
      scenarios in wild populations.

PMID- 21901082
TI  - Inference for nonlinear epidemiological models using genealogies and time series.
AB  - Phylodynamics - the field aiming to quantitatively integrate the ecological and
      evolutionary dynamics of rapidly evolving populations like those of RNA viruses -
      increasingly relies upon coalescent approaches to infer past population dynamics
      from reconstructed genealogies. As sequence data have become more abundant, these
      approaches are beginning to be used on populations undergoing rapid and rather
      complex dynamics. In such cases, the simple demographic models that current
      phylodynamic methods employ can be limiting. First, these models are not ideal
      for yielding biological insight into the processes that drive the dynamics of the
      populations of interest. Second, these models differ in form from mechanistic and
      often stochastic population dynamic models that are currently widely used when
      fitting models to time series data. As such, their use does not allow for both
      genealogical data and time series data to be considered in tandem when conducting
      inference. Here, we present a flexible statistical framework for phylodynamic
      inference that goes beyond these current limitations. The framework we present
      employs a recently developed method known as particle MCMC to fit stochastic,
      nonlinear mechanistic models for complex population dynamics to gene genealogies
      and time series data in a Bayesian framework. We demonstrate our approach using a
      nonlinear Susceptible-Infected-Recovered (SIR) model for the transmission
      dynamics of an infectious disease and show through simulations that it provides
      accurate estimates of past disease dynamics and key epidemiological parameters
      from genealogies with or without accompanying time series data.

PMID- 21901083
TI  - Bistability versus bimodal distributions in gene regulatory processes from
      population balance.
AB  - In recent times, stochastic treatments of gene regulatory processes have appeared
      in the literature in which a cell exposed to a signaling molecule in its
      environment triggers the synthesis of a specific protein through a network of
      intracellular reactions. The stochastic nature of this process leads to a
      distribution of protein levels in a population of cells as determined by a Fokker
      Planck equation. Often instability occurs as a consequence of two (stable) steady
      state protein levels, one at the low end representing the "off" state, and the
      other at the high end representing the "on" state for a given concentration of
      the signaling molecule within a suitable range. A consequence of such bistability
      has been the appearance of bimodal distributions indicating two different
      populations, one in the "off" state and the other in the "on" state. The bimodal
      distribution can come about from stochastic analysis of a single cell. However,
      the concerted action of the population altering the extracellular concentration
      in the environment of individual cells and hence their behavior can only be
      accomplished by an appropriate population balance model which accounts for the
      reciprocal effects of interaction between the population and its environment. In
      this study, we show how to formulate a population balance model in which
      stochastic gene expression in individual cells is incorporated. Interestingly,
      the simulation of the model shows that bistability is neither sufficient nor
      necessary for bimodal distributions in a population. The original notion of
      linking bistability with bimodal distribution from single cell stochastic model
      is therefore only a special consequence of a population balance model.

PMID- 21901085
TI  - Biomedical cloud computing with Amazon Web Services.
AB  - In this overview to biomedical computing in the cloud, we discussed two primary
      ways to use the cloud (a single instance or cluster), provided a detailed example
      using NGS mapping, and highlighted the associated costs. While many users new to
      the cloud may assume that entry is as straightforward as uploading an application
      and selecting an instance type and storage options, we illustrated that there is
      substantial up-front effort required before an application can make full use of
      the cloud's vast resources. Our intention was to provide a set of best practices
      and to illustrate how those apply to a typical application pipeline for
      biomedical informatics, but also general enough for extrapolation to other types
      of computational problems. Our mapping example was intended to illustrate how to
      develop a scalable project and not to compare and contrast alignment algorithms
      for read mapping and genome assembly. Indeed, with a newer aligner such as
      Bowtie, it is possible to map the entire African genome using one m2.2xlarge
      instance in 48 hours for a total cost of approximately $48 in computation time.
      In our example, we were not concerned with data transfer rates, which are heavily
      influenced by the amount of available bandwidth, connection latency, and network
      availability. When transferring large amounts of data to the cloud, bandwidth
      limitations can be a major bottleneck, and in some cases it is more efficient to
      simply mail a storage device containing the data to AWS
      (http://aws.amazon.com/importexport/). More information about cloud computing,
      detailed cost analysis, and security can be found in references.

PMID- 21901084
TI  - Using electronic patient records to discover disease correlations and stratify
      patient cohorts.
AB  - Electronic patient records remain a rather unexplored, but potentially rich data
      source for discovering correlations between diseases. We describe a general
      approach for gathering phenotypic descriptions of patients from medical records
      in a systematic and non-cohort dependent manner. By extracting phenotype
      information from the free-text in such records we demonstrate that we can extend
      the information contained in the structured record data, and use it for producing
      fine-grained patient stratification and disease co-occurrence statistics. The
      approach uses a dictionary based on the International Classification of Disease
      ontology and is therefore in principle language independent. As a use case we
      show how records from a Danish psychiatric hospital lead to the identification of
      disease correlations, which subsequently can be mapped to systems biology
      frameworks.

PMID- 21901080
TI  - The clinical implications of mouse models of enhanced anxiety.
AB  - Mice are increasingly overtaking the rat model organism in important aspects of
      anxiety research, including drug development. However, translating the results
      obtained in mouse studies into information that can be applied in clinics remains
      challenging. One reason may be that most of the studies so far have used animals
      displaying 'normal' anxiety rather than 'psychopathological' animal models with
      abnormal (elevated) anxiety, which more closely reflect core features and
      sensitivities to therapeutic interventions of human anxiety disorders, and which
      would, thus, narrow the translational gap. Here, we discuss manipulations aimed
      at persistently enhancing anxiety-related behavior in the laboratory mouse using
      phenotypic selection, genetic techniques and/or environmental manipulations. It
      is hoped that such models with enhanced construct validity will provide improved
      ways of studying the neurobiology and treatment of pathological anxiety. Examples
      of findings from mouse models of enhanced anxiety-related behavior will be
      discussed, as well as their relation to findings in anxiety disorder patients
      regarding neuroanatomy, neurobiology, genetic involvement and epigenetic
      modifications. Finally, we highlight novel targets for potential anxiolytic
      pharmacotherapeutics that have been established with the help of research
      involving mice. Since the use of psychopathological mouse models is only just
      beginning to increase, it is still unclear as to the extent to which such
      approaches will enhance the success rate of drug development in translating
      identified therapeutic targets into clinical trials and, thus, helping to
      introduce the next anxiolytic class of drugs.

PMID- 21901086
TI  - Podbat: a novel genomic tool reveals Swr1-independent H2A.Z incorporation at gene
      coding sequences through epigenetic meta-analysis.
AB  - Epigenetic regulation consists of a multitude of different modifications that
      determine active and inactive states of chromatin. Conditions such as cell
      differentiation or exposure to environmental stress require concerted changes in
      gene expression. To interpret epigenomics data, a spectrum of different
      interconnected datasets is needed, ranging from the genome sequence and positions
      of histones, together with their modifications and variants, to the
      transcriptional output of genomic regions. Here we present a tool, Podbat
      (Positioning database and analysis tool), that incorporates data from various
      sources and allows detailed dissection of the entire range of chromatin
      modifications simultaneously. Podbat can be used to analyze, visualize, store and
      share epigenomics data. Among other functions, Podbat allows data-driven
      determination of genome regions of differential protein occupancy or RNA
      expression using Hidden Markov Models. Comparisons between datasets are
      facilitated to enable the study of the comprehensive chromatin modification
      system simultaneously, irrespective of data-generating technique. Any organism
      with a sequenced genome can be accommodated. We exemplify the power of Podbat by
      reanalyzing all to-date published genome-wide data for the histone variant H2A.Z
      in fission yeast together with other histone marks and also phenotypic response
      data from several sources. This meta-analysis led to the unexpected finding of
      H2A.Z incorporation in the coding regions of genes encoding proteins involved in
      the regulation of meiosis and genotoxic stress responses. This incorporation was
      partly independent of the H2A.Z-incorporating remodeller Swr1. We verified an
      Swr1-independent role for H2A.Z following genotoxic stress in vivo. Podbat is
      open source software freely downloadable from www.podbat.org, distributed under
      the GNU LGPL license. User manuals, test data and instructions are available at
      the website, as well as a repository for third party-developed plug-in modules.
      Podbat requires Java version 1.6 or higher.

PMID- 21901087
TI  - Are there laws of genome evolution?
AB  - Research in quantitative evolutionary genomics and systems biology led to the
      discovery of several universal regularities connecting genomic and molecular
      phenomic variables. These universals include the log-normal distribution of the
      evolutionary rates of orthologous genes; the power law-like distributions of
      paralogous family size and node degree in various biological networks; the
      negative correlation between a gene's sequence evolution rate and expression
      level; and differential scaling of functional classes of genes with genome size.
      The universals of genome evolution can be accounted for by simple mathematical
      models similar to those used in statistical physics, such as the birth-death
      innovation model. These models do not explicitly incorporate selection;
      therefore, the observed universal regularities do not appear to be shaped by
      selection but rather are emergent properties of gene ensembles. Although a
      complete physical theory of evolutionary biology is inconceivable, the universals
      of genome evolution might qualify as "laws of evolutionary genomics" in the same
      sense "law" is understood in modern physics.

PMID- 21901088
TI  - The plant pathogen Pseudomonas syringae pv. tomato is genetically monomorphic and
      under strong selection to evade tomato immunity.
AB  - Recently, genome sequencing of many isolates of genetically monomorphic bacterial
      human pathogens has given new insights into pathogen microevolution and
      phylogeography. Here, we report a genome-based micro-evolutionary study of a
      bacterial plant pathogen, Pseudomonas syringae pv. tomato. Only 267 mutations
      were identified between five sequenced isolates in 3,543,009 nt of analyzed
      genome sequence, which suggests a recent evolutionary origin of this pathogen.
      Further analysis with genome-derived markers of 89 world-wide isolates showed
      that several genotypes exist in North America and in Europe indicating frequent
      pathogen movement between these world regions. Genome-derived markers and
      molecular analyses of key pathogen loci important for virulence and motility both
      suggest ongoing adaptation to the tomato host. A mutational hotspot was found in
      the type III-secreted effector gene hopM1. These mutations abolish the cell death
      triggering activity of the full-length protein indicating strong selection for
      loss of function of this effector, which was previously considered a virulence
      factor. Two non-synonymous mutations in the flagellin-encoding gene fliC allowed
      identifying a new microbe associated molecular pattern (MAMP) in a region
      distinct from the known MAMP flg22. Interestingly, the ancestral allele of this
      MAMP induces a stronger tomato immune response than the derived alleles. The
      ancestral allele has largely disappeared from today's Pto populations suggesting
      that flagellin-triggered immunity limits pathogen fitness even in highly virulent
      pathogens. An additional non-synonymous mutation was identified in flg22 in South
      American isolates. Therefore, MAMPs are more variable than expected differing
      even between otherwise almost identical isolates of the same pathogen strain.

PMID- 21901089
TI  - Dendritic cell status modulates the outcome of HIV-related B cell disease
      progression.

PMID- 21901090
TI  - Disruption of PML nuclear bodies is mediated by ORF61 SUMO-interacting motifs and
      required for varicella-zoster virus pathogenesis in skin.
AB  - Promyelocytic leukemia protein (PML) has antiviral functions and many viruses
      encode gene products that disrupt PML nuclear bodies (PML NBs). However, evidence
      of the relevance of PML NB modification for viral pathogenesis is limited and
      little is known about viral gene functions required for PML NB disruption in
      infected cells in vivo. Varicella-zoster virus (VZV) is a human alphaherpesvirus
      that causes cutaneous lesions during primary and recurrent infection. Here we
      show that VZV disrupts PML NBs in infected cells in human skin xenografts in SCID
      mice and that the disruption is achieved by open reading frame 61 (ORF61) protein
      via its SUMO-interacting motifs (SIMs). Three conserved SIMs mediated ORF61
      binding to SUMO1 and were required for ORF61 association with and disruption of
      PML NBs. Mutation of the ORF61 SIMs in the VZV genome showed that these motifs
      were necessary for PML NB dispersal in VZV-infected cells in vitro. In vivo, PML
      NBs were highly abundant, especially in basal layer cells of uninfected skin,
      whereas their frequency was significantly decreased in VZV-infected cells. In
      contrast, mutation of the ORF61 SIMs reduced ORF61 association with PML NBs, most
      PML NBs remained intact and importantly, viral replication in skin was severely
      impaired. The ORF61 SIM mutant virus failed to cause the typical VZV lesions that
      penetrate across the basement membrane into the dermis and viral spread in the
      epidermis was limited. These experiments indicate that VZV pathogenesis in skin
      depends upon the ORF61-mediated disruption of PML NBs and that the ORF61 SUMO
      binding function is necessary for this effect. More broadly, our study elucidates
      the importance of PML NBs for the innate control of a viral pathogen during
      infection of differentiated cells within their tissue microenvironment in vivo
      and the requirement for a viral protein with SUMO-binding capacity to counteract
      this intrinsic barrier.

PMID- 21901091
TI  - Viral infection induces expression of novel phased microRNAs from conserved
      cellular microRNA precursors.
AB  - RNA silencing, mediated by small RNAs including microRNAs (miRNAs) and small
      interfering RNAs (siRNAs), is a potent antiviral or antibacterial mechanism,
      besides regulating normal cellular gene expression critical for development and
      physiology. To gain insights into host small RNA metabolism under infections by
      different viruses, we used Solexa/Illumina deep sequencing to characterize the
      small RNA profiles of rice plants infected by two distinct viruses, Rice dwarf
      virus (RDV, dsRNA virus) and Rice stripe virus (RSV, a negative sense and
      ambisense RNA virus), respectively, as compared with those from non-infected
      plants. Our analyses showed that RSV infection enhanced the accumulation of some
      rice miRNA*s, but not their corresponding miRNAs, as well as accumulation of
      phased siRNAs from a particular precursor. Furthermore, RSV infection also
      induced the expression of novel miRNAs in a phased pattern from several conserved
      miRNA precursors. In comparison, no such changes in host small RNA expression was
      observed in RDV-infected rice plants. Significantly RSV infection elevated the
      expression levels of selective OsDCLs and OsAGOs, whereas RDV infection only
      affected the expression of certain OsRDRs. Our results provide a comparative
      analysis, via deep sequencing, of changes in the small RNA profiles and in the
      genes of RNA silencing machinery induced by different viruses in a natural and
      economically important crop host plant. They uncover new mechanisms and
      complexity of virus-host interactions that may have important implications for
      further studies on the evolution of cellular small RNA biogenesis that impact
      pathogen infection, pathogenesis, as well as organismal development.

PMID- 21901092
TI  - The steroid catabolic pathway of the intracellular pathogen Rhodococcus equi is
      important for pathogenesis and a target for vaccine development.
AB  - Rhodococcus equi causes fatal pyogranulomatous pneumonia in foals and
      immunocompromised animals and humans. Despite its importance, there is currently
      no effective vaccine against the disease. The actinobacteria R. equi and the
      human pathogen Mycobacterium tuberculosis are related, and both cause pulmonary
      diseases. Recently, we have shown that essential steps in the cholesterol
      catabolic pathway are involved in the pathogenicity of M. tuberculosis.
      Bioinformatic analysis revealed the presence of a similar cholesterol catabolic
      gene cluster in R. equi. Orthologs of predicted M. tuberculosis virulence genes
      located within this cluster, i.e. ipdA (rv3551), ipdB (rv3552), fadA6 and fadE30,
      were identified in R. equi RE1 and inactivated. The ipdA and ipdB genes of R.
      equi RE1 appear to constitute the alpha-subunit and beta-subunit, respectively,
      of a heterodimeric coenzyme A transferase. Mutant strains RE1DeltaipdAB and
      RE1DeltafadE30, but not RE1DeltafadA6, were impaired in growth on the steroid
      catabolic pathway intermediates 4-androstene-3,17-dione (AD) and 3aalpha-H
      4alpha(3'-propionic acid)-5alpha-hydroxy-7abeta-methylhexahydro-1-indanone
      (5alpha-hydroxy-methylhexahydro-1-indanone propionate; 5OH-HIP). Interestingly,
      RE1DeltaipdAB and RE1DeltafadE30, but not RE1DeltafadA6, also displayed an
      attenuated phenotype in a macrophage infection assay. Gene products important for
      growth on 5OH-HIP, as part of the steroid catabolic pathway, thus appear to act
      as factors involved in the pathogenicity of R. equi. Challenge experiments showed
      that RE1DeltaipdAB could be safely administered intratracheally to 2 to 5 week
      old foals and oral immunization of foals even elicited a substantial protective
      immunity against a virulent R. equi strain. Our data show that genes involved in
      steroid catabolism are promising targets for the development of a live-attenuated
      vaccine against R. equi infections.

PMID- 21901093
TI  - Histo-blood group antigens act as attachment factors of rabbit hemorrhagic
      disease virus infection in a virus strain-dependent manner.
AB  - Rabbit Hemorrhagic disease virus (RHDV), a calicivirus of the Lagovirus genus,
      and responsible for rabbit hemorrhagic disease (RHD), kills rabbits between 48 to
      72 hours post infection with mortality rates as high as 50-90%. Caliciviruses,
      including noroviruses and RHDV, have been shown to bind histo-blood group
      antigens (HBGA) and human non-secretor individuals lacking ABH antigens in
      epithelia have been found to be resistant to norovirus infection. RHDV virus-like
      particles have previously been shown to bind the H type 2 and A antigens. In this
      study we present a comprehensive assessment of the strain-specific binding
      patterns of different RHDV isolates to HBGAs. We characterized the HBGA
      expression in the duodenum of wild and domestic rabbits by mass spectrometry and
      relative quantification of A, B and H type 2 expression. A detailed binding
      analysis of a range of RHDV strains, to synthetic sugars and human red blood
      cells, as well as to rabbit duodenum, a likely gastrointestinal site for viral
      entrance was performed. Enzymatic cleavage of HBGA epitopes confirmed binding
      specificity. Binding was observed to blood group B, A and H type 2 epitopes in a
      strain-dependent manner with slight differences in specificity for A, B or H
      epitopes allowing RHDV strains to preferentially recognize different subgroups of
      animals. Strains related to the earliest described RHDV outbreak were not able to
      bind A, whereas all other genotypes have acquired A binding. In an experimental
      infection study, rabbits lacking the correct HBGA ligands were resistant to
      lethal RHDV infection at low challenge doses. Similarly, survivors of outbreaks
      in wild populations showed increased frequency of weak binding phenotypes,
      indicating selection for host resistance depending on the strain circulating in
      the population. HBGAs thus act as attachment factors facilitating infection,
      while their polymorphism of expression could contribute to generate genetic
      resistance to RHDV at the population level.

PMID- 21901094
TI  - A novel persistence associated EBV miRNA expression profile is disrupted in
      neoplasia.
AB  - We have performed the first extensive profiling of Epstein-Barr virus (EBV)
      miRNAs on in vivo derived normal and neoplastic infected tissues. We describe a
      unique pattern of viral miRNA expression by normal infected cells in vivo
      expressing restricted viral latency programs (germinal center: Latency II and
      memory B: Latency I/0). This includes the complete absence of 15 of the 34 miRNAs
      profiled. These consist of 12 BART miRNAs (including approximately half of
      Cluster 2) and 3 of the 4 BHRF1 miRNAs. All but 2 of these absent miRNAs become
      expressed during EBV driven growth (Latency III). Furthermore, EBV driven growth
      is accompanied by a 5-10 fold down regulation in the level of the BART miRNAs
      expressed in germinal center and memory B cells. Therefore, Latency III also
      expresses a unique pattern of viral miRNAs. We refer to the miRNAs that are
      specifically expressed in EBV driven growth as the Latency III associated miRNAs.
      In EBV associated tumors that employ Latency I or II (Burkitt's lymphoma,
      Hodgkin's disease, nasopharyngeal carcinoma and gastric carcinoma), the Latency
      III associated BART but not BHRF1 miRNAs are up regulated. Thus BART miRNA
      expression is deregulated in the EBV associated tumors. This is the first
      demonstration that Latency III specific genes (the Latency III associated BARTs)
      can be expressed in these tumors. The EBV associated tumors demonstrate very
      similar patterns of miRNA expression yet were readily distinguished when the
      expression data were analyzed either by heat-map/clustering or principal
      component analysis. Systematic analysis revealed that the information
      distinguishing the tumor types was redundant and distributed across all the
      miRNAs. This resembles "secret sharing" algorithms where information can be
      distributed among a large number of recipients in such a way that any combination
      of a small number of recipients is able to understand the message. Biologically,
      this may be a consequence of functional redundancy between the miRNAs.

PMID- 21901095
TI  - Transportin 3 promotes a nuclear maturation step required for efficient HIV-1
      integration.
AB  - The HIV/AIDS pandemic is a major global health threat and understanding the
      detailed molecular mechanisms of HIV replication is critical for the development
      of novel therapeutics. To replicate, HIV-1 must access the nucleus of infected
      cells and integrate into host chromosomes, however little is known about the
      events occurring post-nuclear entry but before integration. Here we show that the
      karyopherin Transportin 3 (Tnp3) promotes HIV-1 integration in different cell
      types. Furthermore Tnp3 binds the viral capsid proteins and tRNAs incorporated
      into viral particles. Interaction between Tnp3, capsid and tRNAs is stronger in
      the presence of RanGTP, consistent with the possibility that Tnp3 is an export
      factor for these substrates. In agreement with this interpretation, we found that
      Tnp3 exports from the nuclei viral tRNAs in a RanGTP-dependent way. Tnp3 also
      binds and exports from the nuclei some species of cellular tRNAs with a defective
      3'CCA end. Depletion of Tnp3 results in a re-distribution of HIV-1 capsid
      proteins between nucleus and cytoplasm however HIV-1 bearing the N74D mutation in
      capsid, which is insensitive to Tnp3 depletion, does not show nucleocytoplasmic
      redistribution of capsid proteins. We propose that Tnp3 promotes HIV-1 infection
      by displacing any capsid and tRNA that remain bound to the pre-integration
      complex after nuclear entry to facilitate integration. The results also provide
      evidence for a novel tRNA nucleocytoplasmic trafficking pathway in human cells.

PMID- 21901097
TI  - Transcriptomic analysis of host immune and cell death responses associated with
      the influenza A virus PB1-F2 protein.
AB  - Airway inflammation plays a major role in the pathogenesis of influenza viruses
      and can lead to a fatal outcome. One of the challenging objectives in the field
      of influenza research is the identification of the molecular bases associated to
      the immunopathological disorders developed during infection. While its precise
      function in the virus cycle is still unclear, the viral protein PB1-F2 is
      proposed to exert a deleterious activity within the infected host. Using an
      engineered recombinant virus unable to express PB1-F2 and its wild-type homolog,
      we analyzed and compared the pathogenicity and host response developed by the two
      viruses in a mouse model. We confirmed that the deletion of PB1-F2 renders the
      virus less virulent. The global transcriptomic analyses of the infected lungs
      revealed a potent impact of PB1-F2 on the response developed by the host. Thus,
      after two days post-infection, PB1-F2 invalidation severely decreased the number
      of genes activated by the host. PB1-F2 expression induced an increase in the
      number and level of expression of activated genes linked to cell death,
      inflammatory response and neutrophil chemotaxis. When generating interactive gene
      networks specific to PB1-F2, we identified IFN-gamma as a central regulator of
      PB1-F2-regulated genes. The enhanced cell death of airway-recruited leukocytes
      was evidenced using an apoptosis assay, confirming the pro-apoptotic properties
      of PB1-F2. Using a NF-kB luciferase adenoviral vector, we were able to quantify
      in vivo the implication of NF-kB in the inflammation mediated by the influenza
      virus infection; we found that PB1-F2 expression intensifies the NF-kB activity.
      Finally, we quantified the neutrophil recruitment within the airways, and showed
      that this type of leukocyte is more abundant during the infection of the wild
      type virus. Collectively, these data demonstrate that PB1-F2 strongly influences
      the early host response during IAV infection and provides new insights into the
      mechanisms by which PB1-F2 mediates virulence.

PMID- 21901096
TI  - Modulation of NKp30- and NKp46-mediated natural killer cell responses by poxviral
      hemagglutinin.
AB  - Natural killer (NK) cells are an important element in the immune defense against
      the orthopox family members vaccinia virus (VV) and ectromelia virus (ECTV). NK
      cells are regulated through inhibitory and activating signaling receptors, the
      latter involving NKG2D and the natural cytotoxicity receptors (NCR), NKp46, NKp44
      and NKp30. Here we report that VV infection results in an upregulation of ligand
      structures for NKp30 and NKp46 on infected cells, whereas the binding of NKp44
      and NKG2D was not significantly affected. Likewise, infection with ectromelia
      virus (ECTV), the mousepox agent, enhanced binding of NKp30 and, to a lesser
      extent, NKp46. The hemagglutinin (HA) molecules from VV and ECTV, which are known
      virulence factors, were identified as novel ligands for NKp30 and NKp46. Using NK
      cells with selectively silenced NCR expression and NCR-CD3zeta reporter cells, we
      observed that HA present on the surface of VV-infected cells, or in the form of
      recombinant soluble protein, was able to block NKp30-triggered activation,
      whereas it stimulated the activation through NKp46. The net effect of this
      complex influence on NK cell activity resulted in a decreased NK lysis
      susceptibility of infected cells at late time points of VV infection when HA was
      expression was pronounced. We conclude that poxviral HA represents a conserved
      ligand of NCR, exerting a novel immune escape mechanism through its blocking
      effect on NKp30-mediated activation at a late stage of infection.

PMID- 21901098
TI  - MrkH, a novel c-di-GMP-dependent transcriptional activator, controls Klebsiella
      pneumoniae biofilm formation by regulating type 3 fimbriae expression.
AB  - Klebsiella pneumoniae causes significant morbidity and mortality worldwide,
      particularly amongst hospitalized individuals. The principle mechanism for
      pathogenesis in hospital environments involves the formation of biofilms,
      primarily on implanted medical devices. In this study, we constructed a
      transposon mutant library in a clinical isolate, K. pneumoniae AJ218, to identify
      the genes and pathways implicated in biofilm formation. Three mutants severely
      defective in biofilm formation contained insertions within the mrkABCDF genes
      encoding the main structural subunit and assembly machinery for type 3 fimbriae.
      Two other mutants carried insertions within the yfiN and mrkJ genes, which encode
      GGDEF domain- and EAL domain-containing c-di-GMP turnover enzymes, respectively.
      The remaining two isolates contained insertions that inactivated the mrkH and
      mrkI genes, which encode for novel proteins with a c-di-GMP-binding PilZ domain
      and a LuxR-type transcriptional regulator, respectively. Biochemical and
      functional assays indicated that the effects of these factors on biofilm
      formation accompany concomitant changes in type 3 fimbriae expression. We mapped
      the transcriptional start site of mrkA, demonstrated that MrkH directly activates
      transcription of the mrkA promoter and showed that MrkH binds strongly to the
      mrkA regulatory region only in the presence of c-di-GMP. Furthermore, a point
      mutation in the putative c-di-GMP-binding domain of MrkH completely abolished its
      function as a transcriptional activator. In vivo analysis of the yfiN and mrkJ
      genes strongly indicated their c-di-GMP-specific function as diguanylate cyclase
      and phosphodiesterase, respectively. In addition, in vitro assays showed that
      purified MrkJ protein has strong c-di-GMP phosphodiesterase activity. These
      results demonstrate for the first time that c-di-GMP can function as an effector
      to stimulate the activity of a transcriptional activator, and explain how type 3
      fimbriae expression is coordinated with other gene expression programs in K.
      pneumoniae to promote biofilm formation to implanted medical devices.

PMID- 21901099
TI  - Pseudomonas evades immune recognition of flagellin in both mammals and plants.
AB  - The building blocks of bacterial flagella, flagellin monomers, are potent
      stimulators of host innate immune systems. Recognition of flagellin monomers
      occurs by flagellin-specific pattern-recognition receptors, such as Toll-like
      receptor 5 (TLR5) in mammals and flagellin-sensitive 2 (FLS2) in plants.
      Activation of these immune systems via flagellin leads eventually to elimination
      of the bacterium from the host. In order to prevent immune activation and thus
      favor survival in the host, bacteria secrete many proteins that hamper such
      recognition. In our search for Toll like receptor (TLR) antagonists, we screened
      bacterial supernatants and identified alkaline protease (AprA) of Pseudomonas
      aeruginosa as a TLR5 signaling inhibitor as evidenced by a marked reduction in IL
      8 production and NF-kappaB activation. AprA effectively degrades the TLR5 ligand
      monomeric flagellin, while polymeric flagellin (involved in bacterial motility)
      and TLR5 itself resist degradation. The natural occurring alkaline protease
      inhibitor AprI of P. aeruginosa blocked flagellin degradation by AprA. P.
      aeruginosa aprA mutants induced an over 100-fold enhanced activation of TLR5
      signaling, because they fail to degrade excess monomeric flagellin in their
      environment. Interestingly, AprA also prevents flagellin-mediated immune
      responses (such as growth inhibition and callose deposition) in Arabidopsis
      thaliana plants. This was due to decreased activation of the receptor FLS2 and
      clearly demonstrated by delayed stomatal closure with live bacteria in plants.
      Thus, by degrading the ligand for TLR5 and FLS2, P. aeruginosa escapes
      recognition by the innate immune systems of both mammals and plants.

PMID- 21901100
TI  - A communal bacterial adhesin anchors biofilm and bystander cells to surfaces.
AB  - While the exopolysaccharide component of the biofilm matrix has been intensively
      studied, much less is known about matrix-associated proteins. To better
      understand the role of these proteins, we undertook a proteomic analysis of the
      V. cholerae biofilm matrix. Here we show that the two matrix-associated proteins,
      Bap1 and RbmA, perform distinct roles in the biofilm matrix. RbmA strengthens
      intercellular attachments. In contrast, Bap1 is concentrated on surfaces where it
      serves to anchor the biofilm and recruit cells not yet committed to the sessile
      lifestyle. This is the first example of a biofilm-derived, communally synthesized
      conditioning film that stabilizes the association of multilayer biofilms with a
      surface and facilitates recruitment of planktonic bystanders to the substratum.
      These studies define a novel paradigm for spatial and functional differentiation
      of proteins in the biofilm matrix and provide evidence for bacterial cooperation
      in maintenance and expansion of the multilayer biofilm.

PMID- 21901101
TI  - Beta-HPV 5 and 8 E6 promote p300 degradation by blocking AKT/p300 association.
AB  - The E6 oncoprotein from high-risk genus alpha human papillomaviruses (alpha
      HPVs), such as HPV 16, has been well characterized with respect to the host-cell
      proteins it interacts with and corresponding signaling pathways that are
      disrupted due to these interactions. Less is known regarding the interacting
      partners of E6 from the genus beta papillomaviruses (beta-HPVs); however, it is
      generally thought that beta-HPV E6 proteins do not interact with many of the
      proteins known to bind to alpha-HPV E6. Here we identify p300 as a protein that
      interacts directly with E6 from both alpha- and beta-HPV types. Importantly, this
      association appears much stronger with beta-HPV types 5 and 8-E6 than with alpha
      HPV type 16-E6 or beta-HPV type 38-E6. We demonstrate that the enhanced
      association between 5/8-E6 and p300 leads to p300 degradation in a proteasomal
      dependent but E6AP-independent manner. Rather, 5/8-E6 inhibit the association of
      AKT with p300, an event necessary to ensure p300 stability within the cell.
      Finally, we demonstrate that the decreased p300 protein levels concomitantly
      affect downstream signaling events, such as the expression of differentiation
      markers K1, K10 and Involucrin. Together, these results demonstrate a unique way
      in which beta-HPV E6 proteins are able to affect host-cell signaling in a manner
      distinct from that of the alpha-HPVs.

PMID- 21901103
TI  - Tumor cell marker PVRL4 (nectin 4) is an epithelial cell receptor for measles
      virus.
AB  - Vaccine and laboratory adapted strains of measles virus can use CD46 as a
      receptor to infect many human cell lines. However, wild type isolates of measles
      virus cannot use CD46, and they infect activated lymphocytes, dendritic cells,
      and macrophages via the receptor CD150/SLAM. Wild type virus can also infect
      epithelial cells of the respiratory tract through an unidentified receptor. We
      demonstrate that wild type measles virus infects primary airway epithelial cells
      grown in fetal calf serum and many adenocarcinoma cell lines of the lung, breast,
      and colon. Transfection of non-infectable adenocarcinoma cell lines with an
      expression vector encoding CD150/SLAM rendered them susceptible to measles virus,
      indicating that they were virus replication competent, but lacked a receptor for
      virus attachment and entry. Microarray analysis of susceptible versus non
      susceptible cell lines was performed, and comparison of membrane protein gene
      transcripts produced a list of 11 candidate receptors. Of these, only the human
      tumor cell marker PVRL4 (Nectin 4) rendered cells amenable to measles virus
      infections. Flow cytometry confirmed that PVRL4 is highly expressed on the
      surfaces of susceptible lung, breast, and colon adenocarcinoma cell lines.
      Measles virus preferentially infected adenocarcinoma cell lines from the apical
      surface, although basolateral infection was observed with reduced kinetics.
      Confocal immune fluorescence microscopy and surface biotinylation experiments
      revealed that PVRL4 was expressed on both the apical and basolateral surfaces of
      these cell lines. Antibodies and siRNA directed against PVRL4 were able to block
      measles virus infections in MCF7 and NCI-H358 cancer cells. A virus binding assay
      indicated that PVRL4 was a bona fide receptor that supported virus attachment to
      the host cell. Several strains of measles virus were also shown to use PVRL4 as a
      receptor. Measles virus infection reduced PVRL4 surface expression in MCF7 cells,
      a property that is characteristic of receptor-associated viral infections.

PMID- 21901102
TI  - Absence of cross-presenting cells in the salivary gland and viral immune evasion
      confine cytomegalovirus immune control to effector CD4 T cells.
AB  - Horizontal transmission of cytomegaloviruses (CMV) occurs via prolonged excretion
      from mucosal surfaces. We used murine CMV (MCMV) infection to investigate the
      mechanisms of immune control in secretory organs. CD4 T cells were crucial to
      cease MCMV replication in the salivary gland (SG) via direct secretion of
      IFNgamma that initiated antiviral signaling on non-hematopoietic cells. In
      contrast, CD4 T cell helper functions for CD8 T cells or B cells were
      dispensable. Despite SG-resident MCMV-specific CD8 T cells being able to produce
      IFNgamma, the absence of MHC class I molecules on infected acinar glandular
      epithelial cells due to viral immune evasion, and the paucity of cross-presenting
      antigen presenting cells (APCs) prevented their local activation. Thus, local
      activation of MCMV-specific T cells is confined to the CD4 subset due to
      exclusive presentation of MCMV-derived antigens by MHC class II molecules on
      bystander APCs, resulting in IFNgamma secretion interfering with viral
      replication in cells of non-hematopoietic origin.

PMID- 21901104
TI  - Global chromosomal structural instability in a subpopulation of starving
      Escherichia coli cells.
AB  - Copy-number variations (CNVs) constitute very common differences between
      individual humans and possibly all genomes and may therefore be important fuel
      for evolution, yet how they form remains elusive. In starving Escherichia coli,
      gene amplification is induced by stress, controlled by the general stress
      response. Amplification has been detected only encompassing genes that confer a
      growth advantage when amplified. We studied the structure of stress-induced gene
      amplification in starving cells in the Lac assay in Escherichia coli by array
      comparative genomic hybridization (aCGH), with polymerase chain reaction (pcr)
      and DNA sequencing to establish the structures generated. About 10% of 300
      amplified isolates carried other chromosomal structural change in addition to
      amplification. Most of these were inversions and duplications associated with the
      amplification event. This complexity supports a mechanism similar to that seen in
      human non-recurrent copy number variants. We interpret these complex events in
      terms of repeated template switching during DNA replication. Importantly, we
      found a significant occurrence (6 out of 300) of chromosomal structural changes
      that were apparently not involved in the amplification event. These secondary
      changes were absent from 240 samples derived from starved cells not carrying
      amplification, suggesting that amplification happens in a differentiated
      subpopulation of stressed cells licensed for global chromosomal structural change
      and genomic instability. These data imply that chromosomal structural changes
      occur in bursts or showers of instability that may have the potential to drive
      rapid evolution.

PMID- 21901105
TI  - Temporal dynamics of host molecular responses differentiate symptomatic and
      asymptomatic influenza a infection.
AB  - Exposure to influenza viruses is necessary, but not sufficient, for healthy human
      hosts to develop symptomatic illness. The host response is an important
      determinant of disease progression. In order to delineate host molecular
      responses that differentiate symptomatic and asymptomatic Influenza A infection,
      we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin) and examined
      changes in host peripheral blood gene expression at 16 timepoints over 132 hours.
      Here we present distinct transcriptional dynamics of host responses unique to
      asymptomatic and symptomatic infections. We show that symptomatic hosts invoke,
      simultaneously, multiple pattern recognition receptors-mediated antiviral and
      inflammatory responses that may relate to virus-induced oxidative stress. In
      contrast, asymptomatic subjects tightly regulate these responses and exhibit
      elevated expression of genes that function in antioxidant responses and cell
      mediated responses. We reveal an ab initio molecular signature that strongly
      correlates to symptomatic clinical disease and biomarkers whose expression
      patterns best discriminate early from late phases of infection. Our results
      establish a temporal pattern of host molecular responses that differentiates
      symptomatic from asymptomatic infections and reveals an asymptomatic host-unique
      non-passive response signature, suggesting novel putative molecular targets for
      both prognostic assessment and ameliorative therapeutic intervention in seasonal
      and pandemic influenza.

PMID- 21901106
TI  - Regulation of Caenorhabditis elegans p53/CEP-1-dependent germ cell apoptosis by
      Ras/MAPK signaling.
AB  - Maintaining genome stability in the germline is thought to be an evolutionarily
      ancient role of the p53 family. The sole Caenorhabditis elegans p53 family member
      CEP-1 is required for apoptosis induction in meiotic, late-stage pachytene germ
      cells in response to DNA damage and meiotic recombination failure. In an unbiased
      genetic screen for negative regulators of CEP-1, we found that increased
      activation of the C. elegans ERK orthologue MPK-1, resulting from either loss of
      the lip-1 phosphatase or activation of let-60 Ras, results in enhanced cep-1
      dependent DNA damage induced apoptosis. We further show that MPK-1 is required
      for DNA damage-induced germ cell apoptosis. We provide evidence that MPK-1
      signaling regulates the apoptotic competency of germ cells by restricting CEP-1
      protein expression to cells in late pachytene. Restricting CEP-1 expression to
      cells in late pachytene is thought to ensure that apoptosis doesn't occur in
      earlier-stage cells where meiotic recombination occurs. MPK-1 signaling regulates
      CEP-1 expression in part by regulating the levels of GLD-1, a translational
      repressor of CEP-1, but also via a GLD-1-independent mechanism. In addition, we
      show that MPK-1 is phosphorylated and activated upon ionising radiation (IR) in
      late pachytene germ cells and that MPK-1-dependent CEP-1 activation may be in
      part direct, as these two proteins interact in a yeast two-hybrid assay. In
      summary, we report our novel finding that MAP kinase signaling controls CEP-1
      dependent apoptosis by several different pathways that converge on CEP-1. Since
      apoptosis is also restricted to pachytene stage cells in mammalian germlines,
      analogous mechanisms regulating p53 family members are likely to be conserved
      throughout evolution.

PMID- 21901107
TI  - Evidence for hitchhiking of deleterious mutations within the human genome.
AB  - Deleterious mutations present a significant obstacle to adaptive evolution.
      Deleterious mutations can inhibit the spread of linked adaptive mutations through
      a population; conversely, adaptive substitutions can increase the frequency of
      linked deleterious mutations and even result in their fixation. To assess the
      impact of adaptive mutations on linked deleterious mutations, we examined the
      distribution of deleterious and neutral amino acid polymorphism in the human
      genome. Within genomic regions that show evidence of recent hitchhiking, we find
      fewer neutral but a similar number of deleterious SNPs compared to other genomic
      regions. The higher ratio of deleterious to neutral SNPs is consistent with
      simulated hitchhiking events and implies that positive selection eliminates some
      deleterious alleles and increases the frequency of others. The distribution of
      disease-associated alleles is also altered in hitchhiking regions. Disease
      alleles within hitchhiking regions have been associated with auto-immune
      disorders, metabolic diseases, cancers, and mental disorders. Our results suggest
      that positive selection has had a significant impact on deleterious polymorphism
      and may be partly responsible for the high frequency of certain human disease
      alleles.

PMID- 21901108
TI  - Specification of Drosophila corpora cardiaca neuroendocrine cells from mesoderm
      is regulated by Notch signaling.
AB  - Drosophila neuroendocrine cells comprising the corpora cardiaca (CC) are
      essential for systemic glucose regulation and represent functional orthologues of
      vertebrate pancreatic alpha-cells. Although Drosophila CC cells have been
      regarded as developmental orthologues of pituitary gland, the genetic regulation
      of CC development is poorly understood. From a genetic screen, we identified
      multiple novel regulators of CC development, including Notch signaling factors.
      Our studies demonstrate that the disruption of Notch signaling can lead to the
      expansion of CC cells. Live imaging demonstrates localized emergence of extra
      precursor cells as the basis of CC expansion in Notch mutants. Contrary to a
      recent report, we unexpectedly found that CC cells originate from head mesoderm.
      We show that Tinman expression in head mesoderm is regulated by Notch signaling
      and that the combination of Daughterless and Tinman is sufficient for ectopic CC
      specification in mesoderm. Understanding the cellular, genetic, signaling, and
      transcriptional basis of CC cell specification and expansion should accelerate
      discovery of molecular mechanisms regulating ontogeny of organs that control
      metabolism.

PMID- 21901109
TI  - Predisposition to cancer caused by genetic and functional defects of mammalian
      Atad5.
AB  - ATAD5, the human ortholog of yeast Elg1, plays a role in PCNA deubiquitination.
      Since PCNA modification is important to regulate DNA damage bypass, ATAD5 may be
      important for suppression of genomic instability in mammals in vivo. To test this
      hypothesis, we generated heterozygous (Atad5(+/m)) mice that were
      haploinsuffficient for Atad5. Atad5(+/m) mice displayed high levels of genomic
      instability in vivo, and Atad5(+/m) mouse embryonic fibroblasts (MEFs) exhibited
      molecular defects in PCNA deubiquitination in response to DNA damage, as well as
      DNA damage hypersensitivity and high levels of genomic instability, apoptosis,
      and aneuploidy. Importantly, 90% of haploinsufficient Atad5(+/m) mice developed
      tumors, including sarcomas, carcinomas, and adenocarcinomas, between 11 and 20
      months of age. High levels of genomic alterations were evident in tumors that
      arose in the Atad5(+/m) mice. Consistent with a role for Atad5 in suppressing
      tumorigenesis, we also identified somatic mutations of ATAD5 in 4.6% of sporadic
      human endometrial tumors, including two nonsense mutations that resulted in loss
      of proper ATAD5 function. Taken together, our findings indicate that loss-of
      function mutations in mammalian Atad5 are sufficient to cause genomic instability
      and tumorigenesis.

PMID- 21901110
TI  - Mutations in fam20b and xylt1 reveal that cartilage matrix controls timing of
      endochondral ossification by inhibiting chondrocyte maturation.
AB  - Differentiating cells interact with their extracellular environment over time.
      Chondrocytes embed themselves in a proteoglycan (PG)-rich matrix, then undergo a
      developmental transition, termed "maturation," when they express ihh to induce
      bone in the overlying tissue, the perichondrium. Here, we ask whether PGs
      regulate interactions between chondrocytes and perichondrium, using zebrafish
      mutants to reveal that cartilage PGs inhibit chondrocyte maturation, which
      ultimately dictates the timing of perichondral bone development. In a mutagenesis
      screen, we isolated a class of mutants with decreased cartilage matrix and
      increased perichondral bone. Positional cloning identified lesions in two genes,
      fam20b and xylosyltransferase1 (xylt1), both of which encode PG synthesis
      enzymes. Mutants failed to produce wild-type levels of chondroitin sulfate PGs,
      which are normally abundant in cartilage matrix, and initiated perichondral bone
      formation earlier than their wild-type siblings. Primary chondrocyte defects
      might induce the bone phenotype secondarily, because mutant chondrocytes
      precociously initiated maturation, showing increased and early expression of such
      markers as runx2b, collagen type 10a1, and ihh co-orthologs, and ihha mutation
      suppressed early perichondral bone in PG mutants. Ultrastructural analyses
      demonstrated aberrant matrix organization and also early cellular features of
      chondrocyte hypertrophy in mutants. Refining previous in vitro reports, which
      demonstrated that fam20b and xylt1 were involved in PG synthesis, our in vivo
      analyses reveal that these genes function in cartilage matrix production and
      ultimately regulate the timing of skeletal development.

PMID- 21901111
TI  - Increased RPA1 gene dosage affects genomic stability potentially contributing to
      17p13.3 duplication syndrome.
AB  - A novel microduplication syndrome involving various-sized contiguous duplications
      in 17p13.3 has recently been described, suggesting that increased copy number of
      genes in 17p13.3, particularly PAFAH1B1, is associated with clinical features
      including facial dysmorphism, developmental delay, and autism spectrum disorder.
      We have previously shown that patient-derived cell lines from individuals with
      haploinsufficiency of RPA1, a gene within 17p13.3, exhibit an impaired ATR
      dependent DNA damage response (DDR). Here, we show that cell lines from patients
      with duplications specifically incorporating RPA1 exhibit a different although
      characteristic spectrum of DDR defects including abnormal S phase distribution,
      attenuated DNA double strand break (DSB)-induced RAD51 chromatin retention,
      elevated genomic instability, and increased sensitivity to DNA damaging agents.
      Using controlled conditional over-expression of RPA1 in a human model cell
      system, we also see attenuated DSB-induced RAD51 chromatin retention.
      Furthermore, we find that transient over-expression of RPA1 can impact on
      homologous recombination (HR) pathways following DSB formation, favouring
      engagement in aberrant forms of recombination and repair. Our data identifies
      unanticipated defects in the DDR associated with duplications in 17p13.3 in
      humans involving modest RPA1 over-expression.

PMID- 21901112
TI  - A pre-mRNA-associating factor links endogenous siRNAs to chromatin regulation.
AB  - In plants and fungi, small RNAs silence gene expression in the nucleus by
      establishing repressive chromatin states. The role of endogenous small RNAs in
      metazoan nuclei is largely unknown. Here we show that endogenous small
      interfering RNAs (endo-siRNAs) direct Histone H3 Lysine 9 methylation (H3K9me) in
      Caenorhabditis elegans. In addition, we report the identification and
      characterization of nuclear RNAi defective (nrde)-1 and nrde-4. Endo-siRNA-driven
      H3K9me requires the nuclear RNAi pathway including the Argonaute (Ago) NRDE-3,
      the conserved nuclear RNAi factor NRDE-2, as well as NRDE-1 and NRDE-4. Small
      RNAs direct NRDE-1 to associate with the pre-mRNA and chromatin of genes, which
      have been targeted by RNAi. NRDE-3 and NRDE-2 are required for the association of
      NRDE-1 with pre-mRNA and chromatin. NRDE-4 is required for NRDE-1/chromatin
      association, but not NRDE-1/pre-mRNA association. These data establish that NRDE
      1 is a novel pre-mRNA and chromatin-associating factor that links small RNAs to
      H3K9 methylation. In addition, these results demonstrate that endo-siRNAs direct
      chromatin modifications via the Nrde pathway in C. elegans.

PMID- 21901113
TI  - Natural polymorphism in BUL2 links cellular amino acid availability with
      chronological aging and telomere maintenance in yeast.
AB  - Aging and longevity are considered to be highly complex genetic traits. In order
      to gain insight into aging as a polygenic trait, we employed an outbred
      Saccharomyces cerevisiae model, generated by crossing a vineyard strain RM11 and
      a laboratory strain S288c, to identify quantitative trait loci that control
      chronological lifespan. Among the major loci that regulate chronological lifespan
      in this cross, one genetic linkage was found to be congruent with a previously
      mapped locus that controls telomere length variation. We found that a single
      nucleotide polymorphism in BUL2, encoding a component of an ubiquitin ligase
      complex involved in trafficking of amino acid permeases, controls chronological
      lifespan and telomere length as well as amino acid uptake. Cellular amino acid
      availability changes conferred by the BUL2 polymorphism alter telomere length by
      modulating activity of a transcription factor Gln3. Among the GLN3
      transcriptional targets relevant to this phenotype, we identified Wtm1, whose
      upregulation promotes nuclear retention of ribonucleotide reductase (RNR)
      components and inhibits the assembly of the RNR enzyme complex during S-phase.
      Inhibition of RNR is one of the mechanisms by which Gln3 modulates telomere
      length. Identification of a polymorphism in BUL2 in this outbred yeast population
      revealed a link among cellular amino acid availability, chronological lifespan,
      and telomere length control.

PMID- 21901115
TI  - Recurrent asymptomatic demyelinating disease following 13-cis-retinoic acid
      exposure.
AB  - We report a case of multifocal demyelination within the central nervous system in
      a patient being treated for a left hemispheric gemnistocytic astrocytoma with
      radiation therapy and chemotherapy, comprising temozolomide (360 mg/day-days 1-5
      every 28 days) and 13-cis-retinoic acid (100 mg/m(2)/day-separated into two doses
      administered every 12 h on days 1 through 21 every 28 days). Five months into her
      first round of chemotherapy, brain magnetic resonance imaging (MRI) demonstrated
      multifocal regions of T2 prolongation with associated gadolinium enhancement
      within the right cerebral hemisphere. Spectroscopic data were consistent with
      demyelination rather than neoplasia. Despite the incidentally identified
      radiological progression, new neurological symptoms were not described. Interval
      resolution of the demyelinating lesions was observed in the years following the
      discontinuance of her chemotherapy regimen with reactivation of the previously
      observed lesions and the development of new T2 foci 6 months into her second
      round of re-treatment for tumour progression 5 years later.

PMID- 21901114
TI  - Distinct Cdk1 requirements during single-strand annealing, noncrossover, and
      crossover recombination.
AB  - Repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) in
      haploid cells is generally restricted to S/G2 cell cycle phases, when DNA has
      been replicated and a sister chromatid is available as a repair template. This
      cell cycle specificity depends on cyclin-dependent protein kinases (Cdk1 in
      Saccharomyces cerevisiae), which initiate HR by promoting 5'-3' nucleolytic
      degradation of the DSB ends. Whether Cdk1 regulates other HR steps is unknown.
      Here we show that yku70Delta cells, which accumulate single-stranded DNA (ssDNA)
      at the DSB ends independently of Cdk1 activity, are able to repair a DSB by
      single-strand annealing (SSA) in the G1 cell cycle phase, when Cdk1 activity is
      low. This ability to perform SSA depends on DSB resection, because both resection
      and SSA are enhanced by the lack of Rad9 in yku70Delta G1 cells. Furthermore, we
      found that interchromosomal noncrossover recombinants are generated in yku70Delta
      and yku70Delta rad9Delta G1 cells, indicating that DSB resection bypasses Cdk1
      requirement also for carrying out these recombination events. By contrast,
      yku70Delta and yku70Delta rad9Delta cells are specifically defective in
      interchromosomal crossover recombination when Cdk1 activity is low. Thus, Cdk1
      promotes DSB repair by single-strand annealing and noncrossover recombination by
      acting mostly at the resection level, whereas additional events require Cdk1
      dependent regulation in order to generate crossover outcomes.

PMID- 21901117
TI  - ACE as a mechanosensor to shear stress influences the control of its own
      regulation via phosphorylation of cytoplasmic Ser(1270).
AB  - OBJECTIVES: We tested whether angiotensin converting enzyme (ACE) and
      phosphorylation of Ser(1270) are involved in shear-stress (SS)-induced
      downregulation of the enzyme. METHODS AND RESULTS: Western blotting analysis
      showed that SS (18 h, 15 dyn/cm(2)) decreases ACE expression and phosphorylation
      as well as p-JNK inhibition in human primary endothelial cells (EC). CHO cells
      expressing wild-type ACE (wt-ACE) also displayed SS-induced decrease in ACE and p
      JNK. Moreover, SS decreased ACE promoter activity in wt-ACE, but had no effect in
      wild type CHO or CHO expressing ACE without either the extra- or the
      intracellular domains, and decreased less in CHO expressing a mutated ACE at
      Ser(1270) compared to wt-ACE (13 vs. 40%, respectively). The JNK inhibitor
      (SP600125, 18 h), in absence of SS, also decreased ACE promoter activity in wt
      ACE. Finally, SS-induced inhibition of ACE expression and phosphorylation in EC
      was counteracted by simultaneous exposure to an ACE inhibitor. CONCLUSIONS: ACE
      displays a key role on its own downregulation in response to SS. This response
      requires both the extra- and the intracellular domains and ACE Ser(1270),
      consistent with the idea that the extracellular domain behaves as a mechanosensor
      while the cytoplasmic domain elicits the downstream intracellular signaling by
      phosphorylation on Ser(1270).

PMID- 21901116
TI  - Whole grain products, fish and bilberries alter glucose and lipid metabolism in a
      randomized, controlled trial: the Sysdimet study.
AB  - BACKGROUND: Due to the growing prevalence of type 2 diabetes, new dietary
      solutions are needed to help improve glucose and lipid metabolism in persons at
      high risk of developing the disease. Herein we investigated the effects of low
      insulin-response grain products, fatty fish, and berries on glucose metabolism
      and plasma lipidomic profiles in persons with impaired glucose metabolism.
      METHODOLOGY/PRINCIPAL FINDINGS: Altogether 106 men and women with impaired
      glucose metabolism and with at least two other features of the metabolic syndrome
      were included in a 12-week parallel dietary intervention. The participants were
      randomized into three diet intervention groups: (1) whole grain and low
      postprandial insulin response grain products, fatty fish three times a week, and
      bilberries three portions per day (HealthyDiet group), (2) Whole grain enriched
      diet (WGED) group, which includes principally the same grain products as group
      (1), but with no change in fish or berry consumption, and (3) refined wheat
      breads (Control). Oral glucose tolerance, plasma fatty acids and lipidomic
      profiles were measured before and after the intervention. Self-reported
      compliance with the diets was good and the body weight remained constant. Within
      the HealthyDiet group two hour glucose concentration and area-under-the-curve for
      glucose decreased and plasma proportion of (n-3) long-chain PUFAs increased
      (False Discovery Rate p-values <0.05). Increases in eicosapentaenoic acid and
      docosahexaenoic acid associated curvilinearly with the improved insulin secretion
      and glucose disposal. Among the 364 characterized lipids, 25 changed
      significantly in the HealthyDiet group, including multiple triglycerides
      incorporating the long chain (n-3) PUFA. CONCLUSIONS/SIGNIFICANCE: The results
      suggest that the diet rich in whole grain and low insulin response grain
      products, bilberries, and fatty fish improve glucose metabolism and alter the
      lipidomic profile. Therefore, such a diet may have a beneficial effect in the
      efforts to prevent type 2 diabetes in high risk persons. TRIAL REGISTRATION:
      ClinicalTrials.gov NCT00573781.

PMID- 21901118
TI  - Aquatic birnavirus-induced ER stress-mediated death signaling contribute to
      downregulation of Bcl-2 family proteins in salmon embryo cells.
AB  - Aquatic birnavirus induces mitochondria-mediated cell death, but whether connects
      to endoplasmic reticulum (ER) stress is still unknown. In this present, we
      characterized that IPNV infection triggers ER stress-mediated cell death via
      PKR/eIF2alpha phosphorylation signaling for regulating the Bcl-2 family protein
      expression in fish cells. The IPNV infection can induce ER stress as follows: (1)
      ER stress sensor ATF6 cleavaged; (2) ER stress marker GRP78 upregulation, and (3)
      PERK/eIF2alpha phosphorylation. Then, the IPNV-induced ER stress signals can
      induce the CHOP expression at early (6 h p.i.) and middle replication (12 h p.i.)
      stages. Moreover, IPNV-induced CHOP upregulation dramatically correlates to
      apparently downregulate the Bcl-2 family proteins, Bcl-2, Mcl-1 and Bcl-xL at
      middle replication stage (12 h p.i.) and produces mitochondria membrane potential
      (MMP) loss and cell death. Furthermore, with GRP78 synthesis inhibitor momitoxin
      (VT) and PKR inhibitor 2-aminopurine (2-AP) treatment for blocking GRP78
      expression and eIF2alpha phosphorylation, PKR/PERK may involve in eIF2alpha
      phosphorylation/CHOP upregulation pathway that enhances the downstream regulators
      Bcl-2 family proteins expression and increased cell survival. Taken together, our
      results suggest that IPNV infection activates PKR/PERK/eIF2alpha ER stress
      signals for regulating downstream molecules CHOP upregulation and Bcl-2 family
      downregulation that led to induce mitochondria-mediated cell death in fish cells,
      which may provide new insight into RNA virus pathogenesis and disease.

PMID- 21901119
TI  - High tumour cannabinoid CB1 receptor immunoreactivity negatively impacts disease
      specific survival in stage II microsatellite stable colorectal cancer.
AB  - BACKGROUND: There is good evidence in the literature that the cannabinoid system
      is disturbed in colorectal cancer. In the present study, we have investigated
      whether CB(1) receptor immunoreactive intensity (CB(1)IR intensity) is associated
      with disease severity and outcome. METHODOLOGY/PRINCIPAL FINDINGS: CB(1)IR was
      assessed in formalin-fixed, paraffin-embedded specimens collected with a
      consecutive intent during primary tumour surgical resection from a series of
      cases diagnosed with colorectal cancer. Tumour centre (n = 483) and invasive
      front (n = 486) CB(1)IR was scored from 0 (absent) to 3 (intense staining) and
      the data was analysed as a median split i.e. CB(1)IR <2 and >=2. In
      microsatellite stable, but not microsatellite instable tumours (as adjudged on
      the basis of immunohistochemical determination of four mismatch repair proteins),
      there was a significant positive association of the tumour grade with the CB(1)IR
      intensity. The difference between the microsatellite stable and instable tumours
      for this association of CB(1)IR was related to the CpG island methylation status
      of the cases. Cox proportional hazards regression analyses indicated a
      significant contribution of CB(1)IR to disease-specific survival in the
      microsatellite stable tumours when adjusting for tumour stage. For the cases with
      stage II microsatellite stable tumours, there was a significant effect of both
      tumour centre and front CB(1)IR upon disease specific survival. The 5 year
      probabilities of event-free survival were: 85+/-5 and 66+/-8%; tumour interior,
      86+/-4% and 63+/-8% for the CB(1)IR<2 and CB(1)IR>=2 groups, respectively.
      CONCLUSIONS/SIGNIFICANCE: The level of CB(1) receptor expression in colorectal
      cancer is associated with the tumour grade in a manner dependent upon the degree
      of CpG hypermethylation. A high CB(1)IR is indicative of a poorer prognosis in
      stage II microsatellite stable tumour patients.

PMID- 21901120
TI  - The redox state of transglutaminase 2 controls arterial remodeling.
AB  - While inward remodeling of small arteries in response to low blood flow,
      hypertension, and chronic vasoconstriction depends on type 2 transglutaminase
      (TG2), the mechanisms of action have remained unresolved. We studied the
      regulation of TG2 activity, its (sub) cellular localization, substrates, and its
      specific mode of action during small artery inward remodeling. We found that
      inward remodeling of isolated mouse mesenteric arteries by exogenous TG2 required
      the presence of a reducing agent. The effect of TG2 depended on its cross-linking
      activity, as indicated by the lack of effect of mutant TG2. The cell-permeable
      reducing agent DTT, but not the cell-impermeable reducing agent TCEP, induced
      translocation of endogenous TG2 and high membrane-bound transglutaminase
      activity. This coincided with inward remodeling, characterized by a stiffening of
      the artery. The remodeling could be inhibited by a TG2 inhibitor and by the
      nitric oxide donor, SNAP. Using a pull-down assay and mass spectrometry, 21
      proteins were identified as TG2 cross-linking substrates, including fibronectin,
      collagen and nidogen. Inward remodeling induced by low blood flow was associated
      with the upregulation of several anti-oxidant proteins, notably glutathione-S
      transferase, and selenoprotein P. In conclusion, these results show that a
      reduced state induces smooth muscle membrane-bound TG2 activity. Inward
      remodeling results from the cross-linking of vicinal matrix proteins, causing a
      stiffening of the arterial wall.

PMID- 21901121
TI  - Molecular evolution of ultraspiracle protein (USP/RXR) in insects.
AB  - Ultraspiracle protein/retinoid X receptor (USP/RXR) is a nuclear receptor and
      transcription factor which is an essential component of a heterodimeric receptor
      complex with the ecdysone receptor (EcR). In insects this complex binds
      ecdysteroids and plays an important role in the regulation of growth,
      development, metamorphosis and reproduction. In some holometabolous insects,
      including Lepidoptera and Diptera, USP/RXR is thought to have experienced several
      important shifts in function. These include the acquisition of novel ligand
      binding properties and an expanded dimerization interface with EcR. In light of
      these recent hypotheses, we implemented codon-based likelihood methods to
      investigate if the proposed shifts in function are reflected in changes in site
      specific evolutionary rates across functional and structural motifs in insect
      USP/RXR sequences, and if there is any evidence for positive selection at
      functionally important sites. Our results reveal evidence of positive selection
      acting on sites within the loop connecting helices H1 and H3, the ligand-binding
      pocket, and the dimer interface in the holometabolous lineage leading to the
      Lepidoptera/Diptera/Trichoptera. Similar analyses conducted using EcR sequences
      did not indicate positive selection. However, analyses allowing for variation
      across sites demonstrated elevated non-synonymous/synonymous rate ratios
      (d(N)/d(S)), suggesting relaxed constraint, within the dimerization interface of
      both USP/RXR and EcR as well as within the coactivator binding groove and helix
      H12 of USP/RXR. Since the above methods are based on the assumption that d(S) is
      constant among sites, we also used more recent models which relax this assumption
      and obtained results consistent with traditional random-sites models. Overall our
      findings support the evolution of novel function in USP/RXR of more derived
      holometabolous insects, and are consistent with shifts in structure and function
      which may have increased USP/RXR reliance on EcR for cofactor recruitment.
      Moreover, these findings raise important questions regarding hypotheses which
      suggest the independent activation of USP/RXR by its own ligand.

PMID- 21901122
TI  - Multicoil2: predicting coiled coils and their oligomerization states from
      sequence in the twilight zone.
AB  - The alpha-helical coiled coil can adopt a variety of topologies, among the most
      common of which are parallel and antiparallel dimers and trimers. We present
      Multicoil2, an algorithm that predicts both the location and oligomerization
      state (two versus three helices) of coiled coils in protein sequences. Multicoil2
      combines the pairwise correlations of the previous Multicoil method with the
      flexibility of Hidden Markov Models (HMMs) in a Markov Random Field (MRF). The
      resulting algorithm integrates sequence features, including pairwise
      interactions, through multinomial logistic regression to devise an optimized
      scoring function for distinguishing dimer, trimer and non-coiled-coil
      oligomerization states; this scoring function is used to produce Markov Random
      Field potentials that incorporate pairwise correlations localized in sequence.
      Multicoil2 significantly improves both coiled-coil detection and dimer versus
      trimer state prediction over the original Multicoil algorithm retrained on a
      newly-constructed database of coiled-coil sequences. The new database, comprised
      of 2,105 sequences containing 124,088 residues, includes reliable structural
      annotations based on experimental data in the literature. Notably, the enhanced
      performance of Multicoil2 is evident when tested in stringent leave-family-out
      cross-validation on the new database, reflecting expected performance on
      challenging new prediction targets that have minimal sequence similarity to known
      coiled-coil families. The Multicoil2 program and training database are available
      for download from http://multicoil2.csail.mit.edu.

PMID- 21901123
TI  - Lipopolysaccharide-binding protein for monitoring of postoperative sepsis:
      complemental to C-reactive protein or redundant?
AB  - INTRODUCTION: To prospectively evaluate the performance of Lipopolysaccharide
      Binding Protein (LBP) in prediction of hospital mortality and its correlation to
      C-reactive Protein (CRP), we studied sixty consecutive, postoperative patients
      with sepsis admitted to the university hospital intensive care unit. MEASUREMENTS
      AND METHODS: Plasma LBP and CRP were serially measured from day(d)1 (onset of
      sepsis) to d14 in parallel with clinical data until d28. Predictive value and
      correlation of LBP and CRP were analyzed by Receiver Operating Characteristic
      (ROC) curve analysis and Pearson's test, respectively. MAIN RESULTS: LBP and CRP
      showed the highest levels on d2 or d3 after the onset of sepsis with no
      significant difference between survivors and nonsurvivors. Only at d7,
      nonsurvivors had significantly (p = .03) higher levels of CRP than survivors.
      Accordingly, in ROC analysis, concentration of CRP and LBP on d7 poorly
      discriminated survivors from nonsurvivors (area under curve = .62 and .55,
      respectively) without significant difference between LBP- and CRP-ROC curves for
      paired comparison. LBP and CRP plasma levels allocated to quartiles correlated
      well with each other (r(2) = .95; p = .02). Likewise, changes in plasma
      concentrations of LBP and CRP from one observation to the next showed a marked
      concordance as both parameters concomitantly increased or decreased in 76% of all
      cases. CONCLUSIONS: During the first 14 days of postoperative sepsis, LBP plasma
      concentrations showed a time course that was very similar to CRP with a high
      concordance in the pattern of day-to-day changes. Furthermore, like CRP, LBP does
      not provide a reliable clue for outcome in this setting.

PMID- 21901124
TI  - A first generation microsatellite- and SNP-based linkage map of Jatropha.
AB  - Jatropha curcas is a potential plant species for biodiesel production. However,
      its seed yield is too low for profitable production of biodiesel. To improve the
      productivity, genetic improvement through breeding is essential. A linkage map is
      an important component in molecular breeding. We established a first-generation
      linkage map using a mapping panel containing two backcross populations with 93
      progeny. We mapped 506 markers (216 microsatellites and 290 SNPs from ESTs) onto
      11 linkage groups. The total length of the map was 1440.9 cM with an average
      marker space of 2.8 cM. Blasting of 222 Jatropha ESTs containing polymorphic SSR
      or SNP markers against EST-databases revealed that 91.0%, 86.5% and 79.2% of
      Jatropha ESTs were homologous to counterparts in castor bean, poplar and
      Arabidopsis respectively. Mapping 192 orthologous markers to the assembled whole
      genome sequence of Arabidopsis thaliana identified 38 syntenic blocks and
      revealed that small linkage blocks were well conserved, but often shuffled. The
      first generation linkage map and the data of comparative mapping could lay a
      solid foundation for QTL mapping of agronomic traits, marker-assisted breeding
      and cloning genes responsible for phenotypic variation.

PMID- 21901125
TI  - Prevention and intervention studies with telmisartan, ramipril and their
      combination in different rat stroke models.
AB  - OBJECTIVES: The effects of AT1 receptor blocker, telmisartan, and the ACE
      inhibitor, ramipril, were tested head-to head and in combination on stroke
      prevention in hypertensive rats and on potential neuroprotection in acute
      cerebral ischemia in normotensive rats. METHODS: Prevention study: Stroke-prone
      spontaneously hypertensive rats (SHR-SP) were subjected to high salt and randomly
      assigned to 4 groups: (1) untreated (NaCl, n = 24), (2) telmisartan (T; n = 27),
      (3) ramipril (R; n = 27) and (4) telmisartan + ramipril (T+R; n = 26). Drug doses
      were selected to keep blood pressure (BP) at 150 mmHg in all groups. Neurological
      signs and stroke incidence at 50% mortality of untreated SHR-SP were
      investigated. Intervention study: Normotensive Wistar rats were treated s.c. 5
      days prior to middle cerebral artery occlusion (MCAO) for 90 min with
      reperfusion. Groups (n = 10 each): (1) sham, (2) vehicle (V; 0.9% NaCl), (3) T
      (0.5 mg/kg once daily), (4) R (0.01 mg/kg twice daily), (5) R (0.1 mg/kg twice
      daily) or (6) T (0.5 mg/kg once daily) plus R (0.01 mg/kg twice daily). Twenty
      four and 48 h after MCAO, neurological outcome (NO) was determined. Forty-eight h
      after MCAO, infarct volume by MRI, neuronal survival, inflammation factors and
      neurotrophin receptor (TrkB) were analysed. RESULTS: Stroke incidence was
      reduced, survival was prolonged and neurological outcome was improved in all
      treated SHR-SP with no differences between treated groups. In the acute
      intervention study, T and T+R, but not R alone, improved NO, reduced infarct
      volume, inflammation (TNFalpha), and induced TrkB receptor and neuronal survival
      in comparison to V. CONCLUSIONS: T, R or T+R had similar beneficial effects on
      stroke incidence and NO in hypertensive rats, confirming BP reduction as
      determinant factor in stroke prevention. In contrast, T and T+R provided superior
      neuroprotection in comparison to R alone in normotensive rats with induced
      cerebral ischemia.

PMID- 21901126
TI  - Entomopathogenic fungi on Hemiberlesia pitysophila.
AB  - Hemiberlesia pitysophila Takagi is an extremely harmful exotic insect in forest
      to Pinus species, including Pinus massoniana. Using both morphological taxonomy
      and molecular phylogenetics, we identified 15 strains of entomogenous fungi,
      which belong to 9 genera with high diversities. Surprisingly, we found that five
      strains that were classified as species of Pestalotiopsis, which has been
      considered plant pathogens and endophytes, were the dominant entomopathogenic
      fungus of H. pitysophila. Molecular phylogenetic tree established by analyzing
      sequences of ribosomal DNA internal transcribed spacer showed that
      entomopathogenic Pestalotiopsis spp. were similar to plant Pestalotiopsis, but
      not to other pathogens and endophytes of its host plant P. massoniana. We were
      the first to isolate entomopathogenic Pestalotiopsis spp. from H. pitysophila.
      Our findings suggest a potential and promising method of H. pitysophila bio
      control.

PMID- 21901127
TI  - A biobrick library for cloning custom eukaryotic plasmids.
AB  - Researchers often require customised variations of plasmids that are not
      commercially available. Here we demonstrate the applicability and versatility of
      standard synthetic biological parts (biobricks) to build custom plasmids. For
      this purpose we have built a collection of 52 parts that include multiple cloning
      sites (MCS) and common protein tags, protein reporters and selection markers,
      amongst others. Importantly, most of the parts are designed in a format to allow
      fusions that maintain the reading frame. We illustrate the collection by building
      several model contructs, including concatemers of protein binding-site motifs,
      and a variety of plasmids for eukaryotic stable cloning and chromosomal
      insertion. For example, in 3 biobrick iterations, we make a cerulean-reporter
      plasmid for cloning fluorescent protein fusions. Furthermore, we use the
      collection to implement a recombinase-mediated DNA insertion (RMDI), allowing
      chromosomal site-directed exchange of genes. By making one recipient stable cell
      line, many standardised cell lines can subsequently be generated, by fluorescent
      fusion-gene exchange. We propose that this biobrick collection may be distributed
      peer-to-peer as a stand-alone library, in addition to its distribution through
      the Registry of Standard Biological Parts (http://partsregistry.org/).

PMID- 21901129
TI  - Moving cages further offshore: effects on southern bluefin tuna, T. maccoyii,
      parasites, health and performance.
AB  - The effects of offshore aquaculture on SBT health (particularly parasitic
      infections and haematology) and performance were the main aim of this study. Two
      cohorts of ranched Southern Bluefin tuna (SBT) (Thunnus maccoyii) were monitored
      throughout the commercial season, one maintained in the traditional near shore
      tuna farming zone and one maintained further offshore. SBT maintained offshore
      had reduced mortality, increased condition index at week 6 post transfer, reduced
      blood fluke and sealice loads, and haematological variables such as haemoglobin
      or lysozyme equal to or exceeding near shore maintained fish. The offshore cohort
      had no Cardicola forsteri and a 5% prevalence of Caligus spp., compared to a
      prevalence of 85% for Cardicola forsteri and 55% prevalence for Caligus spp. near
      shore at 6 weeks post transfer. This study is the first of its kind to examine
      the effects of commercial offshore sites on farmed fish parasites, health and
      performance.

PMID- 21901128
TI  - Ouabain stimulates a Na+/K+-ATPase-mediated SFK-activated signalling pathway that
      regulates tight junction function in the mouse blastocyst.
AB  - The Na(+)/K(+)-ATPase plays a pivotal role during preimplantation development; it
      establishes a trans-epithelial ionic gradient that facilitates the formation of
      the fluid-filled blastocyst cavity, crucial for implantation and successful
      pregnancy. The Na(+)/K(+)-ATPase is also implicated in regulating tight junctions
      and cardiotonic steroid (CTS)-induced signal transduction via SRC. We
      investigated the expression of SRC family kinase (SFK) members, Src and Yes,
      during preimplantation development and determined whether SFK activity is
      required for blastocyst formation. Embryos were collected following super
      ovulation of CD1 or MF1 female mice. RT-PCR was used to detect SFK mRNAs encoding
      Src and Yes throughout preimplantation development. SRC and YES protein were
      localized throughout preimplantation development. Treatment of mouse morulae with
      the SFK inhibitors PP2 and SU6656 for 18 hours resulted in a reversible blockade
      of progression to the blastocyst stage. Blastocysts treated with 10(-3) M ouabain
      for 2 or 10 minutes and immediately immunostained for phosphorylation at SRC
      tyr418 displayed reduced phosphorylation while in contrast blastocysts treated
      with 10(-4) M displayed increased tyr418 fluorescence. SFK inhibition increased
      and SFK activation reduced trophectoderm tight junction permeability in
      blastocysts. The results demonstrate that SFKs are expressed during
      preimplantation development and that SFK activity is required for blastocyst
      formation and is an important mediator of trophectoderm tight junction
      permeability.

PMID- 21901130
TI  - Feeding cues and injected nutrients induce acute expression of multiple clock
      genes in the mouse liver.
AB  - The circadian clock is closely associated with energy metabolism. The liver clock
      can rapidly adapt to a new feeding cycle within a few days, whereas the lung
      clock is gradually entrained over one week. However, the mechanism underlying
      tissue-specific clock resetting is not fully understood. To characterize the
      rapid response to feeding cues in the liver clock, we examined the effects of a
      single time-delayed feeding on circadian rhythms in the liver and lungs of
      Per2::Luc reporter knockin mice. After adapting to a night-time restricted
      feeding schedule, the mice were fed according to a 4, 8, or 13 h delayed schedule
      on the last day. The phase of the liver clock was delayed in all groups with
      delayed feeding, whereas the lung clock remained unaffected. We then examined the
      acute response of clock and metabolism-related genes in the liver using focused
      DNA-microarrays. Clock mutant mice were bred under constant light to attenuate
      the endogenous circadian rhythm, and gene expression profiles were determined
      during 24 h of fasting followed by 8 h of feeding. Per2 and Dec1 were
      significantly increased within 1 h of feeding. Real-time RT-PCR analysis revealed
      a similarly acute response in hepatic clock gene expression caused by feeding
      wild type mice after an overnight fast. In addition to Per2 and Dec1, the
      expression of Per1 increased, and that of Rev-erbalpha decreased in the liver
      within 1 h of feeding after fasting, whereas none of these clock genes were
      affected in the lung. Moreover, an intraperitoneal injection of glucose combined
      with amino acids, but not either alone, reproduced a similar hepatic response.
      Our findings show that multiple clock genes respond to nutritional cues within 1
      h in the liver but not in the lung.

PMID- 21901131
TI  - Herbivory, connectivity, and ecosystem resilience: response of a coral reef to a
      large-scale perturbation.
AB  - Coral reefs world-wide are threatened by escalating local and global impacts, and
      some impacted reefs have shifted from coral dominance to a state dominated by
      macroalgae. Therefore, there is a growing need to understand the processes that
      affect the capacity of these ecosystems to return to coral dominance following
      disturbances, including those that prevent the establishment of persistent stands
      of macroalgae. Unlike many reefs in the Caribbean, over the last several decades,
      reefs around the Indo-Pacific island of Moorea, French Polynesia have
      consistently returned to coral dominance following major perturbations without
      shifting to a macroalgae-dominated state. Here, we present evidence of a rapid
      increase in populations of herbivorous fishes following the most recent
      perturbation, and show that grazing by these herbivores has prevented the
      establishment of macroalgae following near complete loss of coral on offshore
      reefs. Importantly, we found the positive response of herbivorous fishes to
      increased benthic primary productivity associated with coral loss was driven
      largely by parrotfishes that initially recruit to stable nursery habitat within
      the lagoons before moving to offshore reefs later in life. These results
      underscore the importance of connectivity between the lagoon and offshore reefs
      for preventing the establishment of macroalgae following disturbances, and
      indicate that protecting nearshore nursery habitat of herbivorous fishes is
      critical for maintaining reef resilience.

PMID- 21901132
TI  - Treponema denticola major outer sheath protein induces actin assembly at free
      barbed ends by a PIP2-dependent uncapping mechanism in fibroblasts.
AB  - The major outer sheath protein (Msp) of Treponema denticola perturbs actin
      dynamics in fibroblasts by inducing actin reorganization, including subcortical
      actin filament assembly, leading to defective calcium flux, diminished integrin
      engagement of collagen, and retarded cell migration. Yet, its mechanisms of
      action are unknown. We challenged Rat-2 fibroblasts with enriched native Msp. Msp
      activated the small GTPases Rac1, RhoA and Ras, but not Cdc42, yet only Rac1
      localized to areas of actin rearrangement. We used Rac1 dominant negative
      transfection and chemical inhibition of phosphatidylinositol-3 kinase (PI3K) to
      show that even though Rac1 activation was PI3K-dependent, neither was required
      for Msp-induced actin rearrangement. Actin free barbed end formation (FBE) by Msp
      was also PI3K-independent. Immunoblotting experiments showed that gelsolin and
      CapZ were released from actin filaments, whereas cofilin remained in an inactive
      state. Msp induced phosphatidylinositol (4,5)-bisphosphate (PIP2) formation
      through activation of a phosphoinositide 3-phosphatase and its recruitment to
      areas of actin assembly at the plasma membrane. Using a PIP2 binding peptide or
      lipid phosphatase inhibitor, PIP2 was shown to be required for Msp-mediated actin
      uncapping and FBE formation. Evidently, Msp induces actin assembly in fibroblasts
      by production and recruitment of PIP2 and release of the capping proteins CapZ
      and gelsolin from actin barbed ends.

PMID- 21901133
TI  - Association of transcription factor gene LMX1B with autism.
AB  - Multiple lines of evidence suggest a serotoninergic dysfunction in autism. The
      role of LMX1B in the development and maintenance of serotoninergic neurons is
      well known. In order to examine the role, if any, of LMX1B with autism
      pathophysiology, a trio-based SNP association study using 252 family samples from
      the AGRE was performed. Using pair-wise tagging method, 24 SNPs were selected
      from the HapMap data, based on their location and minor allele frequency. Two
      SNPs (rs10732392 and rs12336217) showed moderate association with autism with p
      values 0.018 and 0.022 respectively in transmission disequilibrium test. The
      haplotype AGCGTG also showed significant association (p = 0.008). Further, LMX1B
      mRNA expressions were studied in the postmortem brain tissues of autism subjects
      and healthy controls samples. LMX1B transcripts was found to be significantly
      lower in the anterior cingulate gyrus region of autism patients compared with
      controls (p = 0.049). Our study suggests a possible role of LMX1B in the
      pathophysiology of autism. Based on previous reports, it is likely to be mediated
      through a seretoninergic mechanism. This is the first report on the association
      of LMX1B with autism, though it should be viewed with some caution considering
      the modest associations we report.

PMID- 21901134
TI  - Retinal degeneration progression changes lentiviral vector cell targeting in the
      retina.
AB  - In normal mice, the lentiviral vector (LV) is very efficient to target the RPE
      cells, but transduces retinal neurons well only during development. In the
      present study, the tropism of LV has been investigated in the degenerating retina
      of mice, knowing that the retina structure changes during degeneration. We
      postulated that the viral transduction would be increased by the alteration of
      the outer limiting membrane (OLM). Two different LV pseudotypes were tested using
      the VSVG and the Mokola envelopes, as well as two animal models of retinal
      degeneration: light-damaged Balb-C and Rhodopsin knockout (Rho-/-) mice. After
      light damage, the OLM is altered and no significant increase of the number of
      transduced photoreceptors can be obtained with a LV-VSVG-Rhop-GFP vector. In the
      Rho-/- mice, an alteration of the OLM was also observed, but the possibility of
      transducing photoreceptors was decreased, probably by ongoing gliosis. The use of
      a ubiquitous promoter allows better photoreceptor transduction, suggesting that
      photoreceptor-specific promoter activity changes during late stages of
      photoreceptor degeneration. However, the number of targeted photoreceptors
      remains low. In contrast, LV pseudotyped with the Mokola envelope allows a wide
      dispersion of the vector into the retina (corresponding to the injection bleb)
      with preferential targeting of Muller cells, a situation which does not occur in
      the wild-type retina. Mokola-pseudotyped lentiviral vectors may serve to engineer
      these glial cells to deliver secreted therapeutic factors to a diseased area of
      the retina.

PMID- 21901136
TI  - Graphical approach to model reduction for nonlinear biochemical networks.
AB  - Model reduction is a central challenge to the development and analysis of
      multiscale physiology models. Advances in model reduction are needed not only for
      computational feasibility but also for obtaining conceptual insights from complex
      systems. Here, we introduce an intuitive graphical approach to model reduction
      based on phase plane analysis. Timescale separation is identified by the degree
      of hysteresis observed in phase-loops, which guides a "concentration-clamp"
      procedure for estimating explicit algebraic relationships between species
      equilibrating on fast timescales. The primary advantages of this approach over
      Jacobian-based timescale decomposition are that: 1) it incorporates nonlinear
      system dynamics, and 2) it can be easily visualized, even directly from
      experimental data. We tested this graphical model reduction approach using a 25
      variable model of cardiac beta(1)-adrenergic signaling, obtaining 6- and 4
      variable reduced models that retain good predictive capabilities even in response
      to new perturbations. These 6 signaling species appear to be optimal "kinetic
      biomarkers" of the overall beta(1)-adrenergic pathway. The 6-variable reduced
      model is well suited for integration into multiscale models of heart function,
      and more generally, this graphical model reduction approach is readily applicable
      to a variety of other complex biological systems.

PMID- 21901135
TI  - miR-143 overexpression impairs growth of human colon carcinoma xenografts in mice
      with induction of apoptosis and inhibition of proliferation.
AB  - BACKGROUND: MicroRNAs (miRNAs) are aberrantly expressed in human cancer and
      involved in the (dys)regulation of cell survival, proliferation, differentiation
      and death. Specifically, miRNA-143 (miR-143) is down-regulated in human colon
      cancer. In the present study, we evaluated the role of miR-143 overexpression on
      the growth of human colon carcinoma cells xenografted in nude mice
      (immunodeficient mouse strain: N: NIH(s) II-nu/nu). METHODOLOGY/PRINCIPAL
      FINDINGS: HCT116 cells with stable miR-143 overexpression (Over-143) and control
      (Empty) cells were subcutaneously injected into the flanks of nude mice, and
      tumor growth was evaluated over time. Tumors arose ~ 14 days after tumor cell
      implantation, and the experiment was ended at 40 days after implantation. miR-143
      was confirmed to be significantly overexpressed in Over-143 versus Empty
      xenografts, by TaqMan(r) Real-time PCR (p<0.05). Importantly, Over-143 xenografts
      displayed slower tumor growth compared to Empty xenografts from 23 until 40 days
      in vivo (p<0.05), with final volumes of 928+/-338 and 2512+/-387 mm(3),
      respectively. Evaluation of apoptotic proteins showed that Over-143 versus Empty
      xenografts displayed reduced Bcl-2 levels, and increased caspase-3 activation and
      PARP cleavage (p<0.05). In addition, the incidence of apoptotic tumor cells,
      assessed by TUNEL, was increased in Over-143 versus Empty xenografts (p<0.01).
      Finally, Over-143 versus Empty xenografts displayed significantly reduced NF
      kappaB activation and ERK5 levels and activation (p<0.05), as well as reduced
      proliferative index, evaluated by Ki-67 immunohistochemistry (p<0.01).
      CONCLUSIONS: Our results suggest that reduced tumor volume in Over-143 versus
      Empty xenografts may result from increased apoptosis and decreased proliferation
      induced by miR-143. This reinforces the relevance of miR-143 in colon cancer,
      indicating an important role in the control of in vivo tumor progression, and
      suggesting that miR-143 may constitute a putative novel therapeutic tool for
      colon cancer treatment that warrants further investigation.

PMID- 21901137
TI  - Coordinated regulation of ATF2 by miR-26b in gamma-irradiated lung cancer cells.
AB  - MicroRNA regulates cellular responses to ionizing radiation (IR) through
      translational control of target genes. We analyzed time-series changes in
      microRNA expression following gamma-irradiation in H1299 lung cancer cells using
      microarray analysis. Significantly changed IR-responsive microRNAs were selected
      based on analysis of variance analysis, and predicted target mRNAs were enriched
      in mitogen-activated protein kinase (MAPK) signaling. Concurrent analysis of time
      series mRNA and microRNA profiles uncovered that expression of miR-26b was down
      regulated, and its target activating transcription factor 2 (ATF2) mRNA was up
      regulated in gamma-irradiated H1299 cells. IR in miR-26b overexpressed H1299
      cells could not induce expression of ATF2. When c-Jun N-terminal kinase activity
      was inhibited using SP600125, expression of miR-26b was induced following gamma
      irradiation in H1299 cells. From these results, we concluded that IR-induced up
      regulation of ATF2 was coordinately enhanced by suppression of miR-26b in lung
      cancer cells, which may enhance the effect of IR in the MAPK signaling pathway.

PMID- 21901138
TI  - Computational study of the human dystrophin repeats: interaction properties and
      molecular dynamics.
AB  - Dystrophin is a large protein involved in the rare genetic disease Duchenne
      muscular dystrophy (DMD). It functions as a mechanical linker between the
      cytoskeleton and the sarcolemma, and is able to resist shear stresses during
      muscle activity. In all, 75% of the dystrophin molecule consists of a large
      central rod domain made up of 24 repeat units that share high structural homology
      with spectrin-like repeats. However, in the absence of any high-resolution
      structure of these repeats, the molecular basis of dystrophin central domain's
      functions has not yet been deciphered. In this context, we have performed a
      computational study of the whole dystrophin central rod domain based on the
      rational homology modeling of successive and overlapping tandem repeats and the
      analysis of their surface properties. Each tandem repeat has very specific
      surface properties that make it unique. However, the repeats share enough
      electrostatic-surface similarities to be grouped into four separate clusters.
      Molecular dynamics simulations of four representative tandem repeats reveal
      specific flexibility or bending properties depending on the repeat sequence. We
      thus suggest that the dystrophin central rod domain is constituted of seven
      biologically relevant sub-domains. Our results provide evidence for the role of
      the dystrophin central rod domain as a scaffold platform with a wide range of
      surface features and biophysical properties allowing it to interact with its
      various known partners such as proteins and membrane lipids. This new integrative
      view is strongly supported by the previous experimental works that investigated
      the isolated domains and the observed heterogeneity of the severity of dystrophin
      related pathologies, especially Becker muscular dystrophy.

PMID- 21901139
TI  - Characterization of the major histocompatibility complex class II genes in miiuy
      croaker.
AB  - Major histocompatibility complex (MHC) has a central role in the adaptive immune
      system by presenting foreign peptide to the T-cell receptor. In order to study
      the molecular function and genomic characteristic of class II genes in teleost,
      the full lengths of MHC class IIA and IIB cDNA and genomic sequence were cloned
      from miiuy croaker (Miichthys miiuy). As in other teleost, four exons and three
      introns were identified in miiuy croaker class IIA gene; but the difference is
      that six exons and five introns were identified in the miiuy croaker class IIB
      gene. The deduced amino acid sequence of class IIA and class IIB had 26.3-85.7%
      and 11.0-88.8% identity with those of mammal and teleost, respectively. Real-time
      quantitative RT-PCR demonstrated that the MHC class IIA and IIB were ubiquitously
      expressed in ten normal tissues; expression levels of MHC genes were found first
      upregulated and then downregulated, and finally by a recovery to normal level
      throughout the pathogenic bacteria infection process. In addition, we report on
      the underlying mechanism that maintains sequences diversity among many fish
      species. A series of site-model tests implemented in the CODEML program revealed
      that positive Darwinian selection is likely the cause of the molecular evolution
      in the fish MHC class II genes.

PMID- 21901140
TI  - Mediator subunit 12 is required for neutrophil development in zebrafish.
AB  - Hematopoiesis requires the spatiotemporal organization of regulatory factors to
      successfully orchestrate diverse lineage specificity from stem and progenitor
      cells. Med12 is a regulatory component of the large Mediator complex that enables
      contact between the general RNA polymerase II transcriptional machinery and
      enhancer bound regulatory factors. We have identified a new zebrafish med12
      allele, syr, with a single missense mutation causing a valine to aspartic acid
      change at position 1046. Syr shows defects in hematopoiesis, which predominantly
      affect the myeloid lineage. Syr has identified a hematopoietic cell-specific
      requirement for Med12, suggesting a new role for this transcriptional regulator.

PMID- 21901141
TI  - Impaired OXPHOS complex III in breast cancer.
AB  - We measured the mitochondrial oxidative phosphorylation (mtOXPHOS) activities of
      all five complexes and determined the activity and gene expression in detail of
      the Complex III subunits in human breast cancer cell lines and primary tumors.
      Our analysis revealed dramatic differences in activity of complex III between
      normal and aggressive metastatic breast cancer cell lines. Determination of
      Complex III subunit gene expression identified over expression and co-regulation
      of UQCRFS1 (encoding RISP protein) and UQCRH (encoding Hinge protein) in 6 out of
      9 human breast tumors. Analyses of UQCRFS1/RISP expression in additional matched
      normal and breast tumors demonstrated an over expression in 14 out of 40 (35%)
      breast tumors. UQCRFS1/RISP knockdown in breast tumor cell line led to decreased
      mitochondrial membrane potential as well as a decrease in matrigel invasion.
      Furthermore, reduced matrigel invasion was mediated by reduced ROS levels
      coinciding with decreased expression of NADPH oxidase 2, 3, 4 and 5 involved in
      ROS production. These studies provide direct evidence for contribution of
      impaired mtOXPHOS Complex III to breast tumorigenesis.

PMID- 21901142
TI  - Molecular sites for the positive allosteric modulation of glycine receptors by
      endocannabinoids.
AB  - Glycine receptors (GlyRs) are transmitter-gated anion channels of the Cys-loop
      superfamily which mediate synaptic inhibition at spinal and selected supraspinal
      sites. Although they serve pivotal functions in motor control and sensory
      processing, they have yet to be exploited as drug targets partly because of
      hitherto limited possibilities for allosteric control. Endocannabinoids (ECs)
      have recently been characterized as direct allosteric GlyR modulators, but the
      underlying molecular sites have remained unknown. Here, we show that chemically
      neutral ECs (e.g. anandamide, AEA) are positive modulators of alpha(1), alpha(2)
      and alpha(3) GlyRs, whereas acidic ECs (e.g. N-arachidonoyl-glycine; NA-Gly)
      potentiate alpha(1) GlyRs but inhibit alpha(2) and alpha(3). This subunit
      specificity allowed us to identify the underlying molecular sites through
      analysis of chimeric and mutant receptors. We found that alanine 52 in
      extracellular loop 2, glycine 254 in transmembrane (TM) region 2 and
      intracellular lysine 385 determine the positive modulation of alpha(1) GlyRs by
      NA-Gly. Successive substitution of non-conserved extracellular and TM residues in
      alpha(2) converted NA-Gly-mediated inhibition into potentiation. Conversely,
      mutation of the conserved lysine within the intracellular loop between TM3 and
      TM4 attenuated NA-Gly-mediated potentiation of alpha(1) GlyRs, without affecting
      inhibition of alpha(2) and alpha(3). Notably, this mutation reduced modulation by
      AEA of all three GlyRs. These results define molecular sites for allosteric
      control of GlyRs by ECs and reveal an unrecognized function for the TM3-4
      intracellular loop in the allosteric modulation of Cys-loop ion channels. The
      identification of these sites may help to understand the physiological role of
      this modulation and facilitate the development of novel therapeutic approaches to
      diseases such as spasticity, startle disease and possibly chronic pain.

PMID- 21901143
TI  - Upregulation of cellular Bcl-2 by the KSHV encoded RTA promotes virion
      production.
AB  - Apoptosis of virus infected cells can restrict or dampen full blown virus
      propagation and this can serve as a protective mechanism against virus infection.
      Consequently, viruses can also delay programmed cell death by enhancing the
      expression of anti-apoptotic proteins. Human Bcl-2 is expressed on the surface of
      the mitochondrial membrane and functions as the regulator of the delicate balance
      between cell survival and apoptosis. In this report, we showed that the
      replication and transcription activator (RTA) encoded by KSHV ORF 50, a key
      regulator for KSHV reactivation from latent to lytic infection, upregulates the
      mRNA and protein levels of Bcl-2 in 293 cells, and TPA-induced KSHV-infected
      cells. Further analysis revealed that upregulation of the cellular Bcl-2 promoter
      by RTA is dose-dependent and acts through targeting of the CCN(9)GG motifs within
      the Bcl-2 promoter. The Bcl-2 P2 but not the P1 promoter is primarily responsive
      to RTA. The results of ChIP confirmed the direct interaction of RTA protein with
      the CCN(9)GG motifs. Knockdown of cellular Bcl-2 by lentivirus-delivered small
      hairpin RNA (shRNA) resulted in increased cell apoptosis and decreased virion
      production in KSHV-infected cells. These findings provide an insight into another
      mechanism by which KSHV utilizes the intrinsic apoptosis signaling pathways for
      prolonging the survival of lytically infected host cells to allow for maximum
      production of virus progeny.

PMID- 21901144
TI  - Characteristics of the alternative phenotype of microglia/macrophages and its
      modulation in experimental gliomas.
AB  - Microglia (brain resident macrophages) accumulate in malignant gliomas and
      instead of initiating the anti-tumor response, they switch to a pro-invasive
      phenotype, support tumor growth, invasion, angiogenesis and immunosuppression by
      release of cytokines/chemokines and extracellular matrix proteases. Using
      immunofluorescence and flow cytometry, we demonstrate an early accumulation of
      activated microglia followed by accumulation of macrophages in experimental
      murine EGFP-GL261 gliomas. Those cells acquire the alternative phenotype, as
      evidenced by evaluation of the production of ten pro/anti-inflammatory cytokines
      and expression profiling of 28 genes in magnetically-sorted CD11b(+) cells from
      tumor tissues. Furthermore, we show that infiltration of implanted gliomas by
      amoeboid, Iba1-positive cells can be reduced by a systematically injected
      cyclosporine A (CsA) two or eight days after cell inoculation. The up-regulated
      levels of IL-10 and GM-CSF, increased expression of genes characteristic for the
      alternative and pro-invasive phenotype (arg-1, mt1-mmp, cxcl14) in glioma-derived
      CD11b(+) cells as well as enhanced angiogenesis and tumor growth were reduced in
      CsA-treated mice. Our findings define for the first time kinetics and biochemical
      characteristics of glioma-infiltrating microglia/macrophages. Inhibition of the
      alternative activation of tumor-infiltrating macrophages significantly reduced
      tumor growth. Thus, blockade of microglia/macrophage infiltration and their pro
      invasive functions could be a novel therapeutic strategy in malignant gliomas.

PMID- 21901145
TI  - Diphenyl difluoroketone: a potent chemotherapy candidate for human hepatocellular
      carcinoma.
AB  - Diphenyl difluoroketone (EF24), a molecule having structural similarity to
      curcumin, was recently reported to inhibit proliferation of various cancer cells
      significantly. Here we try to determine the effect and mechanism of EF24 on
      hepatocellular carcinoma. 2 uM EF24 was found to inhibit the proliferation of
      PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 uM EF24
      treatment did not affect the proliferation of normal liver LO2 cells.
      Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts
      conspicuously while causing no apparent change in liver, spleen or body weight.
      In addition, significant apoptosis and G(2)/M phase cell cycle arrest were found
      using flow cytometry. Besides, caspases and PARP activation and features typical
      of apoptosis including fragmented nuclei with condensed chromatin were also
      observed. Furthermore, the mechanism was targeted at the reduction of nuclear
      factor kappa b (NF-kappaB) pathway and the NF-kappaB-regulated gene products Bcl
      2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a
      therapeutic agent for hepatocellular carcinoma.

PMID- 21901146
TI  - Direct observation of single amyloid-beta(1-40) oligomers on live cells: binding
      and growth at physiological concentrations.
AB  - Understanding how amyloid-beta peptide interacts with living cells on a molecular
      level is critical to development of targeted treatments for Alzheimer's disease.
      Evidence that oligomeric Abeta interacts with neuronal cell membranes has been
      provided, but the mechanism by which membrane binding occurs and the exact
      stoichiometry of the neurotoxic aggregates remain elusive. Physiologically
      relevant experimentation is hindered by the high Abeta concentrations required
      for most biochemical analyses, the metastable nature of Abeta aggregates, and the
      complex variety of Abeta species present under physiological conditions. Here we
      use single molecule microscopy to overcome these challenges, presenting direct
      optical evidence that small Abeta(1-40) oligomers bind to living neuroblastoma
      cells at physiological Abeta concentrations. Single particle fluorescence
      intensity measurements indicate that cell-bound Abeta species range in size from
      monomers to hexamers and greater, with the majority of bound oligomers falling in
      the dimer-to-tetramer range. Furthermore, while low-molecular weight oligomeric
      species do form in solution, the membrane-bound oligomer size distribution is
      shifted towards larger aggregates, indicating either that bound Abeta oligomers
      can rapidly increase in size or that these oligomers cluster at specific sites on
      the membrane. Calcium indicator studies demonstrate that small oligomer binding
      at physiological concentrations induces only mild, sporadic calcium leakage.
      These findings support the hypothesis that small oligomers are the primary Abeta
      species that interact with neurons at physiological concentrations.

PMID- 21901147
TI  - An experimental test of condition-dependent male and female mate choice in zebra
      finches.
AB  - In mating systems with social monogamy and obligatory bi-parental care, such as
      found in many songbird species, male and female fitness depends on the combined
      parental investment. Hence, both sexes should gain from choosing mates in high
      rather than low condition. However, theory also predicts that an individual's
      phenotypic quality can constrain choice, if low condition individuals cannot
      afford prolonged search efforts and/or face higher risk of rejection. In systems
      with mutual mate choice, the interaction between male and female condition should
      thus be a better predictor of choice than either factor in isolation. To address
      this prediction experimentally, we manipulated male and female condition and
      subsequently tested male and female mating preferences in zebra finches
      Taeniopygia guttata, a songbird species with mutual mate choice and obligatory bi
      parental care. We experimentally altered phenotypic quality by manipulating the
      brood size in which the birds were reared. Patterns of association for high- or
      low-condition individuals of the opposite sex differed for male and female focal
      birds when tested in an 8-way choice arena. Females showed repeatable condition
      assortative preferences for males matching their own rearing background. Male
      preferences were also repeatable, but not predicted by their own or females'
      rearing background. In combination with a brief review of the literature on
      condition-dependent mate choice in the zebra finch we discuss whether the
      observed sex differences and between-studies differences arise because males and
      females differ in context sensitivity (e.g. male-male competition suppressing
      male mating preferences), sampling strategies or susceptibility to rearing
      conditions (e.g. sex-specific effect on physiology). While a picture emerges that
      juvenile and current state indeed affect preferences, the development and context
      dependency of mutual state-dependent mate choice warrants further study.

PMID- 21901148
TI  - Targeted disruption of TgPhIL1 in Toxoplasma gondii results in altered parasite
      morphology and fitness.
AB  - The inner membrane complex (IMC), a series of flattened vesicles at the periphery
      of apicomplexan parasites, is thought to be important for parasite shape,
      motility and replication, but few of the IMC proteins that function in these
      processes have been identified. TgPhIL1, a Toxoplasma gondii protein that was
      previously identified through photosensitized labeling with 5-[(125)I]
      iodonapthaline-1-azide, associates with the IMC and/or underlying cytoskeleton
      and is concentrated at the apical end of the parasite. Orthologs of TgPhIL1 are
      found in other apicomplexans, but the function of this conserved protein family
      is unknown. As a first step towards determining the function of TgPhIL1 and its
      orthologs, we generated a T. gondii parasite line in which the single copy of
      TgPhIL1 was disrupted by homologous recombination. The TgPhIL1 knockout parasites
      have a distinctly different morphology than wild-type parasites, and normal shape
      is restored in the knockout background after complementation with the wild-type
      allele. The knockout parasites are outcompeted in culture by parasites expressing
      functional TgPhIL1, and they generate a reduced parasite load in the spleen and
      liver of infected mice. These findings demonstrate a role for TgPhIL1 in the
      morphology, growth and fitness of T. gondii tachyzoites.

PMID- 21901149
TI  - Molecular characterization of apricot germplasm from an old stone collection.
AB  - Increasing germplasm erosion requires the recovery and conservation of
      traditional cultivars before they disappear. Here we present a particular case in
      Spain where a thorough prospection of local fruit tree species was performed in
      the 1950s with detailed data of the origin of each genotype but, unfortunately,
      the accessions are no longer conserved in ex situ germplasm collections. However,
      for most of those cultivars, an old stone collection is still preserved. In order
      to analyze the diversity present at the time when the prospection was made and to
      which extent variability has been eroded, we developed a protocol in apricot
      (Prunus armeniaca L.) to obtain DNA from maternal tissues of the stones of a
      sufficient quality to be amplified by PCR. The results obtained have been
      compared with the results from the profiles developed from apricot cultivars
      currently conserved in ex situ germplasm collections. The results highlight the
      fact that most of the old accessions are not conserved ex situ but provide a tool
      to prioritize the recovery of particular cultivars. The approach used in this
      work can also be applied to other plant species where seeds have been preserved.

PMID- 21901150
TI  - Effect of heating and glycation on the allergenicity of 2S albumins (Ara h 2/6)
      from peanut.
AB  - BACKGROUND: Peanut allergy is one of the most common and severe food allergies,
      and processing is known to influence the allergenicity of peanut proteins. We
      aimed to establish the effect of heating and glycation on the IgE-binding
      properties and biological activity of 2S albumins (Ara h 2/6) from peanut.
      METHODOLOGY/PRINCIPAL FINDINGS: Native Ara h 2/6 was purified from raw peanuts
      and heated in solution (15 min, 110 degrees C) in the presence or absence of
      glucose. Ara h 2 and 6 were also purified from roasted peanut. Using PBMC and
      sera from peanut-allergic patients, the cellular proliferative potency and IgE
      reactivity (reverse EAST inhibition) and functionality (basophil degranulation
      capacity) of allergens were assessed. Heating Ara h 2/6 at 110 degrees C resulted
      in extensive denaturation, hydrolysis and aggregation of the protein, whilst Ara
      h 2 and 6 isolated from roasted peanut retained its native conformation. Allergen
      stimulation of PBMC induced proliferation and Th2 cytokine secretion which was
      unaffected by thermal processing. Conversely, IgE reactivity and functionality of
      Ara h 2/6 was decreased by heating. Whilst heating-glycation further reduced the
      IgE binding capacity of the proteins, it moderated their loss of histamine
      releasing capacity. Ara h 2 and 6 purified from roasted peanut demonstrated the
      same IgE reactivity as unheated, native Ara h 2/6. CONCLUSIONS/SIGNIFICANCE:
      Although no effect of processing on T-cell reactivity was observed, heat induced
      denaturation reduced the IgE reactivity and subsequent functionality of Ara h
      2/6. Conversely, Ara h 2 and 6 purified from roasted peanut retained the
      structure and IgE reactivity/functionality of the native protein which may
      explain the allergenic potency of this protein. Through detailed molecular study
      and allergenicity assessment approaches, this work then gives new insights into
      the effect of thermal processing on structure/allergenicity of peanut proteins.

PMID- 21901151
TI  - 3D quantitative imaging of unprocessed live tissue reveals epithelial defense
      against bacterial adhesion and subsequent traversal requires MyD88.
AB  - While a plethora of in vivo models exist for studying infectious disease and its
      resolution, few enable factors involved in the maintenance of health to be
      studied in situ. This is due in part to a paucity of tools for studying
      subtleties of bacterial-host interactions at a cellular level within live organs
      or tissues, requiring investigators to rely on overt outcomes (e.g. pathology) in
      their research. Here, a suite of imaging technologies were combined to enable 3D
      and temporal subcellular localization and quantification of bacterial
      distribution within the murine cornea without the need for tissue processing or
      dissection. These methods were then used to demonstrate the importance of MyD88,
      a central adaptor protein for Toll-Like Receptor (TLR) mediated signaling, in
      protecting a multilayered epithelium against both adhesion and traversal by the
      opportunistic bacterial pathogen Pseudomonas aeruginosa ex vivo and in vivo.

PMID- 21901152
TI  - Protein C mutation (A267T) results in ER retention and unfolded protein response
      activation.
AB  - BACKGROUND: Protein C (PC) deficiency is associated with a high risk of venous
      thrombosis. Recently, we identified the PC-A267T mutation in a patient with PC
      deficiency and revealed by in vitro studies decreased intracellular and secreted
      levels of the mutant. The aim of the present study was to characterize the
      underlying mechanism(s). METHODOLOGY/PRINCIPAL FINDINGS: CHO-K1 cells stably
      expressing the wild-type (PC-wt) or the PC mutant were generated. In order to
      examine whether the PC mutant was subjected to increased intracellular
      degradation, the cells were treated with several inhibitors of various
      degradation pathways and pulse-chase experiments were performed. Protein
      chaperone complexes were analyzed by treating the cells with a cross-linker
      followed by Western blotting (WB). Expression levels of the immunoglobulin
      binding protein (BiP) and the phosphorylated eukaryotic initiation factor 2alpha
      (P-eIF2alpha), both common ER stress markers, were determined by WB to examine if
      the mutation induced ER stress and unfolded protein response (UPR) activation. We
      found no major differences in the intracellular degradation between the PC
      variants. The PC mutant was retained in the endoplasmic reticulum (ER) and had
      increased association with the Grp-94 and calreticulin chaperones. Retention of
      the PC-A267T in ER resulted in UPR activation demonstrated by increased
      expression levels of the ER stress markers BiP and P-eIF2alpha and caused also
      increased apoptotic activity in CHO-K1 cells as evidenced by elevated levels of
      DNA fragmentation. CONCLUSIONS/SIGNIFICANCE: The reduced intracellular level and
      impaired secretion of the PC mutant were due to retention in ER. In contrast to
      other PC mutations, retention of the PC-A267T in ER resulted in minor increased
      proteasomal degradation, rather it induced ER stress, UPR activation and
      apoptosis.

PMID- 21901153
TI  - The lipid-sensor candidates CD36 and GPR120 are differentially regulated by
      dietary lipids in mouse taste buds: impact on spontaneous fat preference.
AB  - BACKGROUND: Recent studies in rodents and humans suggest that the chemoreception
      of long-chain fatty acids (LCFA) in oral cavity is involved in the spontaneous
      preference for fatty foods and might contribute to the obesity risk. CD36 and
      GPR120 are LCFA receptors identified in rodent taste bud cells. The fact that
      CD36 or GPR120 gene inactivation leads to a decrease in the preference for lipids
      raises the question of the respective role(s) played by these gustatory lipid
      sensor candidates. METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of
      biochemical, nutritional and behavioural studies in wild-type, CD36(+/-)and CD36(
      /-) mice, it was found that: 1 degrees ) CD36 and GPR120 display different
      diurnal rhythms in the gustatory circumvallate papillae, CD36 mRNA levels being
      down-regulated during the dark period in contrast to GPR120, 2 degrees ) this
      change is due to food intake and strictly dependent of the presence of lipids in
      the diet, 3 degrees ) CD36 protein levels are also rapidly but transiently
      decreased by the food intake, a two-fold drop in CD36 protein levels being found
      1 h after refeeding, followed by a progressive return to the pre-prandial values,
      4 degrees ) this down-regulation, which has a post-transcriptional origin, seems
      sufficient to alter the spontaneous fat preference, independently to change in
      the GPR120 gene expression. CONCLUSIONS/SIGNIFICANCE: In contrast to GPR120, CD36
      appears to be a food-sensitive lipid sensor in the gustatory circumvallate
      papillae. Lipid-mediated change in lingual CD36 expression might modulate the
      motivation for fat during a meal, initially high and then gradually decreasing
      secondary to the food intake. This short-term lipid-mediated effect is
      reminiscent of sensory-specific satiety. These findings, which highlight the role
      played by CD36 in the oro-sensory perception of dietary lipids, raise the
      possibility of novel pharmacological strategies to modify attraction for fatty
      foods and decrease obesity risks.

PMID- 21901154
TI  - Odour maps in the brain of butterflies with divergent host-plant preferences.
AB  - Butterflies are believed to use mainly visual cues when searching for food and
      oviposition sites despite that their olfactory system is morphologically similar
      to their nocturnal relatives, the moths. The olfactory ability in butterflies
      has, however, not been thoroughly investigated. Therefore, we performed the first
      study of odour representation in the primary olfactory centre, the antennal
      lobes, of butterflies. Host plant range is highly variable within the butterfly
      family Nymphalidae, with extreme specialists and wide generalists found even
      among closely related species. Here we measured odour evoked Ca(2+) activity in
      the antennal lobes of two nymphalid species with diverging host plant
      preferences, the specialist Aglais urticae and the generalist Polygonia c-album.
      The butterflies responded with stimulus-specific combinations of activated
      glomeruli to single plant-related compounds and to extracts of host and non-host
      plants. In general, responses were similar between the species. However, the
      specialist A. urticae responded more specifically to its preferred host plant,
      stinging nettle, than P. c-album. In addition, we found a species-specific
      difference both in correlation between responses to two common green leaf
      volatiles and the sensitivity to these compounds. Our results indicate that these
      butterflies have the ability to detect and to discriminate between different
      plant-related odorants.

PMID- 21901155
TI  - MEF2C enhances dopaminergic neuron differentiation of human embryonic stem cells
      in a parkinsonian rat model.
AB  - Human embryonic stem cells (hESCs) can potentially differentiate into any cell
      type, including dopaminergic neurons to treat Parkinson's disease (PD), but
      hyperproliferation and tumor formation must be avoided. Accordingly, we use
      myocyte enhancer factor 2C (MEF2C) as a neurogenic and anti-apoptotic
      transcription factor to generate neurons from hESC-derived neural stem/progenitor
      cells (NPCs), thus avoiding hyperproliferation. Here, we report that forced
      expression of constitutively active MEF2C (MEF2CA) generates significantly
      greater numbers of neurons with dopaminergic properties in vitro. Conversely,
      RNAi knockdown of MEF2C in NPCs decreases neuronal differentiation and dendritic
      length. When we inject MEF2CA-programmed NPCs into 6-hydroxydopamine-lesioned
      parkinsonian rats in vivo, the transplanted cells survive well, differentiate
      into tyrosine hydroxylase-positive neurons, and improve behavioral deficits to a
      significantly greater degree than non-programmed cells. The enriched generation
      of dopaminergic neuronal lineages from hESCs by forced expression of MEF2CA in
      the proper context may prove valuable in cell-based therapy for CNS disorders
      such as PD.

PMID- 21901156
TI  - Lowe Syndrome protein OCRL1 supports maturation of polarized epithelial cells.
AB  - Mutations in the inositol polyphosphate 5-phosphatase OCRL1 cause Lowe Syndrome,
      leading to cataracts, mental retardation and renal failure. We noted that cell
      types affected in Lowe Syndrome are highly polarized, and therefore we studied
      OCRL1 in epithelial cells as they mature from isolated individual cells into
      polarized sheets and cysts with extensive communication between neighbouring
      cells. We show that a proportion of OCRL1 targets intercellular junctions at the
      early stages of their formation, co-localizing both with adherens junctional
      components and with tight junctional components. Correlating with this
      distribution, OCRL1 forms complexes with junctional components alpha-catenin and
      zonula occludens (ZO)-1/2/3. Depletion of OCRL1 in epithelial cells growing as a
      sheet inhibits maturation; cells remain flat, fail to polarize apical markers and
      also show reduced proliferation. The effect on shape is reverted by re-expressed
      OCRL1 and requires the 5'-phosphatase domain, indicating that down-regulation of
      5-phosphorylated inositides is necessary for epithelial development. The effect
      of OCRL1 in epithelial maturation is seen more strongly in 3-dimensional
      cultures, where epithelial cells lacking OCRL1 not only fail to form a central
      lumen, but also do not have the correct intracellular distribution of ZO-1,
      suggesting that OCRL1 functions early in the maturation of intercellular
      junctions when cells grow as cysts. A role of OCRL1 in junctions of polarized
      cells may explain the pattern of organs affected in Lowe Syndrome.

PMID- 21901157
TI  - Recapitulation of fibromatosis nodule by multipotential stem cells in
      immunodeficient mice.
AB  - Musculoskeletal fibromatosis remains a disease of unknown etiology. Surgical
      excision is the standard of care, but the recurrence rate remains high.
      Superficial fibromatosis typically presents as subcutaneous nodules caused by
      rapid myofibroblast proliferation followed by slow involution to dense acellular
      fibrosis. In this study, we demonstrate that fibromatosis stem cells (FSCs) can
      be isolated from palmar nodules but not from cord or normal palm tissues. We
      found that FSCs express surface markers such as CD29, CD44, CD73, CD90, CD105,
      and CD166 but do not express CD34, CD45, or CD133. We also found that FSCs are
      capable of expanding up to 20 passages, that these cells include myofibroblasts,
      osteoblasts, adipocytes, chondrocytes, hepatocytes, and neural cells, and that
      these cells possess multipotentiality to develop into the three germ layer cells.
      When implanted beneath the dorsal skin of nude mice, FSCs recapitulated human
      fibromatosis nodules. Two weeks after implantation, the cells expressed
      immunodiagnostic markers for myofibroblasts such as alpha-smooth muscle actin and
      type III collagen. Two months after implantation, there were fewer myofibroblasts
      and type I collagen became evident. Treatment with the antifibrogenic compound
      Trichostatin A (TSA) inhibited the proliferation and differentiation of FSCs in
      vitro. Treatment with TSA before or after implantation blocked formation of
      fibromatosis nodules. These results suggest that FSCs are the cellular origin of
      fibromatosis and that these cells may provide a promising model for developing
      new therapeutic interventions.

PMID- 21901158
TI  - Genome-wide detection of allele specific copy number variation associated with
      insulin resistance in African Americans from the HyperGEN study.
AB  - African Americans have been understudied in genome wide association studies of
      diabetes and related traits. In the current study, we examined the joint
      association of single nucleotide polymorphisms (SNPs) and copy number variants
      (CNVs) with fasting insulin and an index of insulin resistance (HOMA-IR) in the
      HyperGEN study, a family based study with proband ascertainment for hypertension.
      This analysis is restricted to 1,040 African Americans without diabetes. We
      generated allele specific CNV genotypes at 872,243 autosomal loci using
      Birdsuite, a freely available multi-stage program. Joint tests of association for
      SNPs and CNVs were performed using linear mixed models adjusting for covariates
      and familial relationships. Our results highlight SNPs associated with fasting
      insulin and HOMA-IR (rs6576507 and rs8026527, 3.7*10(-7)<=P<=1.1*10(-5)) near
      ATPase, class V, type 10A (ATP10A), and the L Type voltage dependent calcium
      channel (CACNA1D, rs1401492, P<=5.2*10(-6)). ATP10A belongs to a family of
      aminophospholipid-transporting ATPases and has been associated with type 2
      diabetes in mice. CACNA1D has been linked to pancreatic beta cell generation in
      mice. The two most significant copy variable markers (rs10277702 and rs361367;
      P<2.0*10(-4)) were in the beta variable region of the T-cell receptor gene
      (TCRVB). Human and mouse TCR has been shown to mimic insulin and its receptor and
      could contribute to insulin resistance. Our findings differ from genome wide
      association studies of fasting insulin and other diabetes related traits in
      European populations, highlighting the continued need to investigate unique
      genetic influences for understudied populations such as African Americans.

PMID- 21901159
TI  - Serratia marcescens is able to survive and proliferate in autophagic-like
      vacuoles inside non-phagocytic cells.
AB  - Serratia marcescens is an opportunistic human pathogen that represents a growing
      problem for public health, particularly in hospitalized or immunocompromised
      patients. However, little is known about factors and mechanisms that contribute
      to S. marcescens pathogenesis within its host. In this work, we explore the
      invasion process of this opportunistic pathogen to epithelial cells. We
      demonstrate that once internalized, Serratia is able not only to persist but also
      to multiply inside a large membrane-bound compartment. This structure displays
      autophagic-like features, acquiring LC3 and Rab7, markers described to be
      recruited throughout the progression of antibacterial autophagy. The majority of
      the autophagic-like vacuoles in which Serratia resides and proliferates are non
      acidic and have no degradative properties, indicating that the bacteria are
      capable to either delay or prevent fusion with lysosomal compartments, altering
      the expected progression of autophagosome maturation. In addition, our results
      demonstrate that Serratia triggers a non-canonical autophagic process before
      internalization. These findings reveal that S. marcescens is able to manipulate
      the autophagic traffic, generating a suitable niche for survival and
      proliferation inside the host cell.

PMID- 21901161
TI  - Patterns of gene expression in Drosophila InsP3 receptor mutant larvae reveal a
      role for InsP3 signaling in carbohydrate and energy metabolism.
AB  - BACKGROUND: The Inositol 1,4,5-trisphosphate receptor (InsP(3)R) is an InsP(3)
      gated intracellular Ca(2+)-release channel. Characterization of Drosophila
      mutants for the InsP(3)R has demonstrated that InsP(3)-mediated Ca(2+) release is
      required in Drosophila larvae for growth and viability. METHODOLOGY/PRINCIPAL
      FINDINGS: To understand the molecular basis of these growth defects a genome wide
      microarray analysis has been carried out with larval RNA obtained from a strong
      InsP(3)R mutant combination in which 1504 independent genes were differentially
      regulated with a log(2) of fold change of 1 or more and P<0.05. This was followed
      by similar transcript analyses from InsP(3)R mutants where growth defects were
      either suppressed by introduction of a dominant suppressor or rescued by ectopic
      expression of an InsP(3)R transgene in the Drosophila insulin like peptide-2
      (Dilp2) producing cells. CONCLUSIONS/SIGNIFICANCE: These studies show that
      expression of transcripts related to carbohydrate and amine metabolism is altered
      in InsP(3) receptor mutant larvae. Moreover, from a comparative analysis of genes
      that are regulated in the suppressed and rescued conditions with the mutant
      condition, it appears that the organism could use different combinations of
      pathways to restore a 'normal' growth state.

PMID- 21901160
TI  - Maternal obesity during gestation impairs fatty acid oxidation and mitochondrial
      SIRT3 expression in rat offspring at weaning.
AB  - In utero exposure to maternal obesity increases the offspring's risk of obesity
      in later life. We have also previously reported that offspring of obese rat dams
      develop hepatic steatosis, mild hyperinsulinemia, and a lipogenic gene signature
      in the liver at postnatal day (PND)21. In the current study, we examined systemic
      and hepatic adaptations in male Sprague-Dawley offspring from lean and obese dams
      at PND21. Indirect calorimetry revealed decreases in energy expenditure (p<0.001)
      and increases in RER values (p<0.001), which were further exacerbated by high fat
      diet (45% kcals from fat) consumption indicating an impaired ability to utilize
      fatty acids in offspring of obese dams as analyzed by PRCF. Mitochondrial
      function is known to be associated with fatty acid oxidation (FAO) in the liver.
      Several markers of hepatic mitochondrial function were reduced in offspring of
      obese dams. These included SIRT3 mRNA (p = 0.012) and mitochondrial protein
      content (p = 0.002), electron transport chain complexes (II, III, and ATPase),
      and fasting PGC-1alpha mRNA expression (p<0.001). Moreover, hepatic LCAD, a SIRT3
      target, was not only reduced 2-fold (p<0.001) but was also hyperacetylated in
      offspring of obese dams (p<0.005) suggesting decreased hepatic FAO. In
      conclusion, exposure to maternal obesity contributes to early perturbations in
      whole body and liver energy metabolism. Mitochondrial dysfunction may be an
      underlying event that reduces hepatic fatty acid oxidation and precedes the
      development of detrimental obesity associated co-morbidities such as insulin
      resistance and NAFLD.

PMID- 21901163
TI  - Asymmetry in species regional dispersal ability and the neutral theory.
AB  - The neutral assumption that individuals of either the same or different species
      share exactly the same birth, death, migration, and speciation probabilities is
      fundamental yet controversial to the neutral theory. Several theoretical studies
      have demonstrated that a slight difference in species per capita birth or death
      rates can have a profound consequence on species coexistence and community
      structure. Whether asymmetry in migration, a vital demographic parameter in the
      neutral model, plays an important role in community assembly still remains
      unknown. In this paper, we relaxed the ecological equivalence assumption of the
      neutral model by introducing differences into species regional dispersal ability.
      We investigated the effect of asymmetric dispersal on the neutral local community
      structure. We found that per capita asymmetric dispersal among species could
      reduce species richness of the local community and result in deviations of
      species abundance distributions from those predicted by the neutral model. But
      the effect was moderate compared with that of asymmetries in birth or death
      rates, unless very large asymmetries in dispersal were assumed. A large
      difference in species dispersal ability, if there is, can overwhelm the role of
      random drift and make local community dynamics deterministic. In this case,
      species with higher regional dispersal abilities tended to dominate in the local
      community. However, the species abundance distribution of the local community
      under asymmetric dispersal could be well fitted by the neutral model, but the
      neutral model generally underestimated the fundamental biodiversity number but
      overestimated the migration rate in such communities.

PMID- 21901162
TI  - Molecular genetic analysis of 103 sporadic colorectal tumours in Czech patients.
AB  - The Czech Republic has one of the highest incidences of colorectal cancer (CRC)
      in Europe. To evaluate whether sporadic CRCs in Czech patients have specific
      mutational profiles we analysed somatic genetic changes in known CRC genes (APC,
      KRAS, TP53, CTNNB1, MUTYH and BRAF, loss of heterozygosity (LOH) at the APC
      locus, microsatellite instability (MSI), and methylation of the MLH1 promoter) in
      103 tumours from 102 individuals. The most frequently mutated gene was APC (68.9%
      of tumours), followed by KRAS (31.1%), TP53 (27.2%), BRAF (8.7%) and CTNNB1
      (1.9%). Heterozygous germline MUTYH mutations in 2 patients were unlikely to
      contribute to the development of their CRCs. LOH at the APC locus was found in
      34.3% of tumours, MSI in 24.3% and MLH1 methylation in 12.7%. Seven tumours
      (6.9%) were without any changes in the genes tested. The analysis yielded several
      findings possibly specific for the Czech cohort. Somatic APC mutations did not
      cluster in the mutation cluster region (MCR). Tumours with MSI but no MLH1
      methylation showed earlier onset and more severe mutational profiles compared to
      MSI tumours with MLH1 methylation. TP53 mutations were predominantly located
      outside the hot spots, and transitions were underrepresented. Our analysis
      supports the observation that germline MUTYH mutations are rare in Czech
      individuals with sporadic CRCs. Our findings suggest the influence of specific
      ethnic genetic factors and/or lifestyle and dietary habits typical for the Czech
      population on the development of these cancers.

PMID- 21901164
TI  - Inactivation of a single copy of Crebbp selectively alters pre-mRNA processing in
      mouse hematopoietic stem cells.
AB  - Global expression analysis of fetal liver hematopoietic stem cells (FL HSCs)
      revealed the presence of unspliced pre-mRNA for a number of genes in normal FL
      HSCs. In a subset of these genes, Crebbp+/- FL HSCs had less unprocessed pre-mRNA
      without a corresponding reduction in total mRNA levels. Among the genes thus
      identified were the key regulators of HSC function Itga4, Msi2 and Tcf4. A
      similar but much weaker effect was apparent in Ep300+/- FL HSCs, indicating that,
      in this context as in others, the two paralogs are not interchangeable. As a
      group, the down-regulated intronic probe sets could discriminate adult HSCs from
      more mature cell types, suggesting that the underlying mechanism is regulated
      with differentiation stage and is active in both fetal and adult hematopoiesis.
      Consistent with increased myelopoiesis in Crebbp hemizygous mice, targeted
      reduction of CREBBP abundance by shRNA in the multipotent EML cell line triggered
      spontaneous myeloid differentiation in the absence of the normally required
      inductive signals. In addition, differences in protein levels between
      phenotypically distinct EML subpopulations were better predicted by taking into
      account not only the total mRNA signal but also the amount of unspliced message
      present. CREBBP thus appears to selectively influence the timing and degree of
      pre-mRNA processing of genes essential for HSC regulation and thereby has the
      potential to alter subsequent cell fate decisions in HSCs.

PMID- 21901165
TI  - No evidence for early modulation of evoked responses in primary visual cortex to
      irrelevant probe stimuli presented during the attentional blink.
AB  - BACKGROUND: During rapid serial visual presentation (RSVP), observers often miss
      the second of two targets if it appears within 500 ms of the first. This
      phenomenon, called the attentional blink (AB), is widely held to reflect a
      bottleneck in the processing of rapidly sequential stimuli that arises after
      initial sensory registration is complete (i.e., at a relatively late, post
      perceptual stage of processing). Contrary to this view, recent fMRI studies have
      found that activity in the primary visual area (V1), which represents the
      earliest cortical stage of visual processing, is attenuated during the AB. Here
      we asked whether such changes in V1 activity during the AB arise in the initial
      feedforward sweep of stimulus input, or instead reflect the influence of feedback
      signals from higher cortical areas. METHODOLOGY/PRINCIPAL FINDINGS: EEG signals
      were recorded while participants monitored a sequential stream of distractor
      letters for two target digits (T1 and T2). Neural responses associated with an
      irrelevant probe stimulus presented simultaneously with T2 were measured using an
      ERP marker--the C1 component--that reflects initial perceptual processing of
      visual information in V1. As expected, T2 accuracy was compromised when the inter
      target interval was brief, reflecting an AB deficit. Critically, however, the
      magnitude of the early C1 component evoked by the probe was not reduced during
      the AB. CONCLUSIONS/SIGNIFICANCE: Our finding that early sensory processing of
      irrelevant probe stimuli is not suppressed during the AB is consistent with
      theoretical models that assume that the bottleneck underlying the AB arises at a
      post-perceptual stage of processing. This suggests that reduced neural activity
      in V1 during the AB is driven by re-entrant signals from extrastriate areas that
      regulate early cortical activity via feedback connections with V1.

PMID- 21901166
TI  - The Role of BH3-Only Proteins in Tumor Cell Development, Signaling, and
      Treatment.
AB  - Tumor cells have devised several strategies to block the mitochondrial pathway of
      apoptosis despite endogenous or pharmacological cues to die. This process of cell
      death proceeds through the coordinated regulation of multiple anti-apoptotic and
      pro-apoptotic BCL-2 family proteins that ultimately impinge on the integrity of
      the outer mitochondrial membrane. Once compromised, mitochondria release pro
      apoptotic factors to promote caspase activation and the apoptotic phenotype.
      Within the BCL-2 family exists a subclass of pro-apoptotic members termed the BH3
      only proteins, which directly and/or indirectly functionally regulate the
      remaining anti- and pro-apoptotic BCL-2 proteins to compromise mitochondria and
      engage apoptosis. The focus of this review is to discuss the cellular and
      pharmacological regulation of the BH3-only proteins to gain a better
      understanding of the signaling pathways and agents that regulate this class of
      proteins. As the BH3-only proteins increase cellular sensitivity to pro-apoptotic
      agents such as chemotherapeutics, numerous small-molecule BH3 mimetics have been
      developed and are currently in various phases of clinical trials. Toward the end
      of the review, the discovery and application of the small-molecule BH3 mimetics
      will be discussed.

PMID- 21901167
TI  - Cooperative Cross-Talk between Neuroblastoma Subtypes Confers Resistance to
      Anaplastic Lymphoma Kinase Inhibition.
AB  - Neuroblastoma is a pediatric solid tumor that can be stratified into stroma-rich
      and stroma-poor histological subgroups. The stromal compartment of neuroblastoma
      is composed mostly of Schwann cells, and they play critical roles in the
      differentiation, survival, and angiogenic responses of tumor cells. In certain
      neuroblastoma cell lines, the coexistence of neuroblastic N-type and substrate
      adherent S-type is frequently observed. One such cell line, SK-N-SH, harbors a
      F1174L oncogenic mutation in the anaplastic lymphoma kinase (ALK) gene. Treatment
      of SK-N-SH with an ALK chemical inhibitor, TAE684, resulted in the outgrowth of S
      type cells that expressed the Schwann cell marker, S100alpha6. Nucleotide
      sequencing analysis of these TAE684-resistant (TR) sublines revealed the presence
      of the ALK F1174L mutation, suggesting their tumor origin, although ALK protein
      was not detected. Consistent with these findings, TR cells displayed
      approximately 9-fold higher IC(50) values than N-type cells. Also, unlike N-type
      cells, TR cells have readily detectable phosphorylated STAT3 but weaker
      phosphorylated AKT. Under coculture conditions, TR cells conferred survival to N
      type cells against the apoptotic effect of TAE684. Cocultivation also greatly
      enhanced the overall phosphorylation of STAT3 and its transcriptional activity in
      N-type cells. Finally, conditioned medium from TR clones enhanced cell viability
      of N-type cells, and this effect was phosphatidylinositol 3-kinase dependent.
      Taken together, these results demonstrate the ability of tumor-derived S-type
      cells in protecting N-type cells against the apoptotic effect of an ALK kinase
      inhibitor through upregulating prosurvival signaling.

PMID- 21901168
TI  - Identification of an In Vivo MEK/WOX1 Complex as a Master Switch for Apoptosis in
      T Cell Leukemia.
AB  - Not all leukemia T cells are susceptible to high levels of phorbol myristate
      acetate (PMA)-mediated apoptosis. At micromolar levels, PMA induces apoptosis of
      Jurkat T cells by causing mitochondrial polarization/de-polarization, release of
      cytosolic granules, and DNA fragmentation. Chemical inhibitors U0126 and PD98059
      block mitogen-activated protein kinase kinase 1 (MEK1)-mediated phosphorylation
      of extracellular signal-regulated kinase (ERK) and prevent apoptosis.
      Mechanistically, proapoptotic tumor suppressor WOX1 (also named WWOX or FOR)
      physically interacts with MEK1, in part, in the lysosomes in Jurkat cells. PMA
      induces the dissociation, which leads to relocation of MEK1 to lipid rafts and
      WOX1 to the mitochondria for causing apoptosis. U0126 inhibits PMA-induced
      dissociation of WOX1/MEK1 complex and supports survival of Jurkat cells. In
      contrast, less differentiated Molt-4 T cells are resistant to PMA-induced
      dissociation of the WOX1/MEK1 complex and thereby are refractory to apoptosis.
      U0126 overturns the resistance for enhancing apoptosis in Molt-4 cells. Together,
      the in vivo MEK1/WOX1 complex is a master on/off switch for apoptosis in leukemia
      T cells.

PMID- 21901169
TI  - Lysophosphatidic Acid Stimulates the Proliferation of Ovarian Cancer Cells via
      the gep Proto-Oncogene Galpha(12).
AB  - Lysophosphatidic acid (LPA), an agonist that activates specific G protein-coupled
      receptors, is present at an elevated concentration in the serum and ascitic fluid
      of ovarian cancer patients. Although the increased levels of LPA have been linked
      to the genesis and progression of different cancers including ovarian carcinomas,
      the specific signaling conduit utilized by LPA in promoting different aspects of
      oncogenic growth has not been identified. Here, we show that LPA stimulates both
      migration and proliferation of ovarian cancer cells. Using multiple approaches,
      we demonstrate that the stimulation of ovarian cancer cells with LPA results in a
      robust and statistically significant proliferative response. Our results also
      indicate that Galpha(12), the gep proto-oncogene, which can be stimulated by LPA
      via specific LPA receptors, is overtly activated in a large array of ovarian
      cancer cells. We further establish that LPA stimulates the rapid activation of
      Galpha(12) in SKOV-3 cells and the expression of CT12, an inhibitory minigene of
      Galpha(12) that disrupts LPAR-Galpha(12) interaction and potently inhibits such
      activation. Using this inhibitory molecule as well as the shRNA approach, we show
      that the inhibition of Galpha(12) or silencing of its expression drastically and
      significantly attenuates LPA-mediated proliferation of ovarian cancer cell lines
      such as SKOV3, Hey, and OVCAR-3. Together with our findings that the silencing of
      Galpha(12) does not have any significant effect on LPA-mediated migratory
      response of SKOV3 cells, our results point to a critical role for LPA-LPAR
      Galpha(12) signaling in ovarian cancer cell proliferation and not in migration.
      Thus, results presented here for the first time demonstrate that the gep proto
      oncogene forms a specific node in LPA-LPAR-mediated mitogenic signaling in
      ovarian cancer cells.

PMID- 21901170
TI  - Ranpirnase Interferes with NF-kappaB Pathway and MMP9 Activity, Inhibiting
      Malignant Mesothelioma Cell Invasiveness and Xenograft Growth.
AB  - The ribonuclease ranpirnase (Onconase) has been used empirically to treat
      malignant mesothelioma (MM) patients, and some of them had prolonged survivals.
      The aim of this study was to investigate the mechanisms of the therapeutic
      function of ranpirnase in MM cells. The effects of ranpirnase were studied in
      vivo and in vitro on 2 MM cell lines (epithelioid REN and sarcomatoid PPM-Mill).
      We found that ranpirnase was able to inhibit NF-kappaB nuclear translocation,
      evaluated by cell fractionation and immunoblotting as well as by
      immunofluorescence. Also, MMP9 secretion by MM cells was decreased by ranpirnase
      treatment, as assessed by the reduction of metalloproteinase activity, evaluated
      by zymography on culture-conditioned media. Ranpirnase induced apoptosis of MM
      cells in vitro and in vivo, causing a powerful inhibition of MM tumor growth in
      SCID xenografts, determined by In Vivo Imaging System (IVIS) of tumor cells
      engineered by lentiviral transduction of the luciferase gene. Finally, mice
      treated with ranpirnase showed a significantly prolonged survival. Our data
      provide a mechanistic rationale to explain the beneficial antitumor activity
      observed in some patients treated with ranpirnase and demonstrate that ranpirnase
      interferes with the NF-kappaB pathway, thus influencing MM tumor cell
      invasiveness and survival. It is hoped that this information will also facilitate
      the identification of those patients who are more likely to benefit from this
      drug and will also open a new frontier for the use of this drug in tumor types
      other than MM.

PMID- 21901171
TI  - Critical Role of c-Myc in Acute Myeloid Leukemia Involving Direct Regulation of
      miR-26a and Histone Methyltransferase EZH2.
AB  - Increased expression or aberrant activation of c-Myc plays an important role in
      leukemogenesis. Here, we show that in acute myeloid leukemia (AML), c-Myc
      directly controls the expression of EZH2, a component of the Polycomb repressive
      complex 2, and miR-26a. miR-26a is downregulated in primary blasts from AML
      patients and, during myeloid differentiation of AML cells, is induced together
      with a decrease in c-Myc and Ezh2 levels. Previously, EZH2 was shown to be
      regulated by miR-26a at the translational levels in lymphomas. However, we
      demonstrate that in AML, the variation of EZH2 mainly depends on c-Myc
      transcriptional control. We also show that enforced expression of miR-26a in AML
      cells is able to inhibit cell cycle progression by downregulating cyclin E2
      expression. In addition, increased levels of miR-26a potentiate the
      antiproliferative effects of 1,25-dihydroxyvitamin D(3) (VitD) and stimulate
      myeloid differentiation. Our results identify new molecular targets of c-Myc in
      AML and highlight miR-26a attractiveness as a therapeutic target in leukemia.

PMID- 21901172
TI  - LIF, a Novel STAT5-Regulated Gene, Is Aberrantly Expressed in Myeloproliferative
      Neoplasms.
AB  - A search for genes potentially regulated by STAT5 identified leukemia inhibitory
      factor (LIF) as a good candidate. Using various experimental approaches, we have
      validated LIF as a direct transcriptional target of STAT5 in myeloid cell lines:
      STAT5 binds to LIF promoter, and LIF expression is increased after activation of
      the JAK2/STAT5 pathway. We also found that LIF expression is significantly
      increased in patients with chronic myeloproliferative neoplasms with and without
      activating mutations of the pathway, indicating that LIF might play an important
      role in STAT5-mediated oncogenesis.

PMID- 21901173
TI  - Self Reports of Day-to-Day Function in a Small Cohort of People with Prodromal
      and Early HD.
AB  - Day-to-day functioning is a component of health-related quality of life and is an
      important end point for therapies to treat Huntington Disease (HD). Specific
      areas of day-to-day function changes have not been reported for prodromal or very
      early stages of HD. An exploratory self-report telephone interview was conducted
      with sixteen people with prodromal HD or early HD who met criteria designed to
      capture research participants most near to motor diagnosis. All completed semi
      structured interviews on function in nine aspects of day-to-day life. Out of 16,
      14 reported changes in at least one area. All day-to-day function areas were
      endorsed by at least one participant with driving being the most common area
      endorsed by 11/16. Changes in ability to perform some day-to-day tasks are
      experienced by people who are close to the time of clinical diagnosis for HD.
      Functional ability is likely to be an important component of outcome assessments
      of clinical trials and in ongoing clinical management.

PMID- 21901174
TI  - Chronic hepatitis B infection: a workshop consensus statement and algorithm.
AB  - Here, presented with an evidence-based algorithm, are workshop consensus
      recommendations on whom to screen for hepatitis B and when to pursue further
      evaluation and management.

PMID- 21901175
TI  - The rebirth of the solo family doc.

PMID- 21901176
TI  - A stroke -- or something else?
AB  - The patient -- who'd had a CVA the year before -- was experiencing numbness and
      weakness in her right leg and foot, and had an increasingly unsteady gait.
      Initial lab work provided no clues.

PMID- 21901177
TI  - Aspirin for CV prevention -- for which patients?
AB  - Put your patient on aspirin? Take him off? Here's what you need to know to get it
      right.

PMID- 21901178
TI  - The mammography controversy: when should you screen?
AB  - ACOG's new guidelines call for more frequent breast cancer screening. The USPSTF
      recommends less. What's best for your patients?

PMID- 21901179
TI  - PURLs: statins for patients with nonalcoholic fatty liver?
AB  - Although physicians often avoid prescribing statins for patients with
      nonalcoholic fatty liver, their use has been found to reduce cardiovascular
      morbidity and mortality- and to lower liver enzymes.

PMID- 21901180
TI  - Pruritic rash on trunk.
AB  - The patient had been treated with topical antifungals and steroids without
      relief, but a more detailed history suggested a serious infectious etiology.

PMID- 21901181
TI  - Ready for flu season? The 2011-2012 ACIP recommendations.
AB  - Strains in this year's vaccine are identical to last year's, but revaccination is
      strongly recommended. Also, the dosing decision for children < 9 years has been
      simplified.

PMID- 21901182
TI  - Clinical inquiry: what risk factors contribute to C difficile diarrhea?
AB  - Certain antibiotics and using 3 or more antibiotics at one time are associated
      with Clostridium difficile-associated diarrhea. Hospital risk factors include
      proximity to other patients with C difficile and longer length of stay. Patient
      risk factors include advanced age and comorbid conditions. Acid suppression
      medication is also a risk factor for CDAD.

PMID- 21901183
TI  - Clinical inquiry: does brief physician counseling promote weight loss?
AB  - In some cases, it may. While physician counseling alone isn't more effective for
      weight loss than usual care, counseling (adults) as part of a multidisciplinary
      intervention may promote modest (2-3 kg) weight loss over 1 year.

PMID- 21901184
TI  - Clinical inquiry: what's the best way to relieve mastitis in breastfeeding
      mothers?
AB  - Frequent breast emptying helps both infectious and noninfectious mastitis.
      Antibiotics may be useful for women with positive milk cultures, but their
      utility for treating undifferentiated mastitis is unknown. Consider prescribing
      antibiotics for women whose mastitis symptoms don' t improve after 12 to 24 hours
      of frequent breast emptying.

PMID- 21901185
TI  - On the chemical processing of hydrocarbon surfaces by fast oxygen ions.
AB  - Solid methane (CH(4)), ethane (C(2)H(6)), and ethylene (C(2)H(4)) ices
      (thickness: 120 +/- 40 nm; 10 K), as well as high-density polyethylene (HDPE:
      [C(2)H(4)](n)) films (thickness: 130 +/- 20 nm; 10, 100, and 300 K), were
      irradiated with mono-energetic oxygen ions (Phi ~ 6 * 10(15) cm(-2)) of a kinetic
      energy of 5 keV to simulate the exposure of Solar System hydrocarbon ices and
      aerospace polymers to oxygen ions sourced from the solar wind and planetary
      magnetospheres. On-line Fourier-transform infrared spectroscopy (FTIR) was used
      to identify the following O(+) induced reaction pathways in the solid-state: (i)
      ethane formation from methane ice via recombination of methyl (CH(3)) radicals,
      (ii) ethane conversion back to methane via methylene (CH(2)) retro-insertion,
      (iii) ethane decomposing to acetylene via ethylene through successive hydrogen
      elimination steps, and (iv) ethylene conversion to acetylene via hydrogen
      elimination. No changes were observed in the irradiated PE samples via infrared
      spectroscopy. In addition, mass spectrometry detected small abundances of
      methanol (CH(3)OH) sublimed from the irradiated methane and ethane condensates
      during controlled heating. The detection of methanol suggests an implantation and
      neutralization of the oxygen ions within the surface where atomic oxygen (O) then
      undergoes insertion into a C-H bond of methane. Atomic hydrogen (H) recombination
      in forming molecular hydrogen and recombination of implanted oxygen atoms to
      molecular oxygen (O(2)) are also inferred to proceed at high cross-sections. A
      comparison of the reaction rates and product yields to those obtained from
      experiments involving 5 keV electrons, suggests that the chemical alteration of
      the hydrocarbon ice samples is driven primarily by electronic stopping
      interactions and to a lesser extent by nuclear interactions.

PMID- 21901187
TI  - Biomimetic fibronectin/mineral and osteogenic growth peptide/mineral composites
      synthesized on calcium phosphate thin films.
AB  - Composites of fibronectin/mineral and osteogenic growth peptide/mineral were
      synthesized on calcium phosphate coated substrates immersed in Dulbecco's
      phosphate-buffered saline solution containing biomolecules. The kinetics of
      coprecipitation for two biomolecules was similar, and the biomolecules
      participated in the formation of the crystal latticework and influenced the
      mineral structure and composition.

PMID- 21901186
TI  - Bacterial ATP-driven transporters of transition metals: physiological roles,
      mechanisms of action, and roles in bacterial virulence.
AB  - Maintaining adequate intracellular levels of transition metals is fundamental to
      the survival of all organisms. While all transition metals are toxic at elevated
      intracellular concentrations, metals such as iron, zinc, copper, and manganese
      are essential to many cellular functions. In prokaryotes, the concerted action of
      a battery of membrane-embedded transport proteins controls a delicate balance
      between sufficient acquisition and overload. Representatives from all major
      families of transporters participate in this task, including ion-gradient driven
      systems and ATP-utilizing pumps. P-type ATPases and ABC transporters both utilize
      the free energy of ATP hydrolysis to drive transport. Each of these very
      different families of transport proteins has a distinct role in maintaining
      transition metal homeostasis: P-type ATPases prevent intracellular overloading of
      both essential and toxic metals through efflux while ABC transporters import
      solely the essential ones. In the present review we discuss how each system is
      adapted to perform its specific task from mechanistic and structural
      perspectives. Despite the mechanistic and structural differences between P-type
      ATPases and ABC transporters, there is one important commonality: in many
      clinically relevant bacterial pathogens, transporters of transition metals are
      essential for virulence. Here we present several such examples and discuss how
      these may be exploited for future antibacterial drug development.

PMID- 21901188
TI  - Site-selective DNA hydrolysis induced by a metal-free peptide nucleic acid-cyclen
      conjugate.
AB  - A metal-free artificial restriction DNA cutter which is composed of cyclen and
      classical peptide nucleic acid (PNA) was synthesized. Analysis of DNA cleavage
      products indicates the site-selective hydrolysis.

PMID- 21901189
TI  - Developing transboundary river basin monitoring programmes using the DPSIR
      indicator framework.
AB  - Policymakers are often dissatisfied by the lack of what they consider useful
      information to support water management. Analysis of this 'water information gap'
      shows that this is caused by a lack of proper communication between information
      users and information producers. To improve this communication the process of
      specification of information needs has been structured. Earlier experiences
      showed that this not only entailed developing a structure to manage the process,
      but also developing a structure to guide the breakdown of policy objectives into
      information needs. Such a structure to organise the problem supports policy
      makers and monitoring specialists in their communication. This paper describes
      three pilot projects where the DPSIR indicator framework was used to organise the
      problem. It is concluded that the DPSIR framework is useful for improving the
      communication between information users and information producers and is helpful
      in breaking down policy objectives into information needs in a structured way.
      The structured approach in this way assists in narrowing the water information
      gap. Use of the DPSIR framework however leads to a bias towards water management
      problems and does not provide for all the relevant information needs.

PMID- 21901190
TI  - Photophysical and quantum chemical study on a J-aggregate forming perylene
      bisimide monomer.
AB  - Perylene bisimides (PBIs) are excellent dyes and versatile building blocks for
      supramolecular structures. Only recently have PBIs been shown to depict
      absorption characteristics of J-aggregates. We apply electronic structure
      calculations and femtosecond pump-probe spectroscopy to the monomeric, bay
      substituted building-block of a PBI aggregate in dichloromethane to investigate
      its electronically excited states in order to provide the ingredients for the
      description of excitons in the aggregates and their annihilation processes. The
      PBI S(1)<-S(0) absorption spectrum and the S(1)->S(0) emission spectrum have been
      assigned based on time-dependent Density Functional Theory calculations for the
      geometry-optimized electronic ground state and excited state structures in the
      gas phase. The monomeric absorption spectrum contains a strong transition at 580
      nm and a broad shoulder between 575-500 nm, both features are attributed to a
      vibrational progression with an effective vibrational mode of 1415 cm(-1) whose
      major contributing vibrational normal modes are breathing modes of the perylene
      body. The effective vibrational mode of the emission spectrum is characterized by
      a frequency of 1369 cm(-1), whose major contributing vibrational normal modes are
      characterized by perylene and phenol (bay-substituent) CH bendings. The S(n)<
      S(1) excited state absorption spectrum is assigned based on Multi-Reference
      Configuration Interaction methodology. Here, we identify three transitions which
      give rise to two broad experimental features, one being located between 500 and
      600 nm and the other one ranging from 650 to 750 nm.

PMID- 21901192
TI  - Binding modes of oxalate in UO2(oxalate) in aqueous solution studied with first
      principles molecular dynamics simulations. Implications for the chelate effect.
AB  - Car-Parrinello molecular dynamics simulations are reported for aqueous
      UO(2)(H(2)O)(n)(C(2)O(4)) (n = 3, 4), calling special attention to the binding
      modes of oxalate and the thermodynamics of the so-called chelate effect. Based on
      free energies from thermodynamic integration (BLYP functional), the
      kappa(1),kappa(1')-binding mode of the oxalate (with one O atom from each
      carboxylate coordinating) is more stable than kappa(2) (2 O atoms from the same
      carboxylate) and kappa(1) forms by 23 and 39 kJ mol(-1), respectively. The free
      energy of binding a fourth water ligand to UO(2)(H(2)O)(3)(kappa(1)-C(2)O(4)) is
      computed to be low, 12 kJ mol(-1). Changes of the hydration shell about oxalate
      during chelate opening are discussed. Composite enthalpies and free energies,
      obtained from both experiment and quantum-chemical modeling, are proposed for the
      formation of monodentate UO(2)(H(2)O)(4)(kappa(1)-C(2)O(4)). These data suggest
      that the largest entropy change in the overall complex formation occurs at this
      stage, and that the subsequent chelate closure under water release is essentially
      enthalpy-driven.

PMID- 21901191
TI  - Conformational changes of non-B DNA.
AB  - In contrast to B-DNA that has a right-handed double helical structure with Watson
      Crick base pairing under the ordinary physiological conditions, repetitive DNA
      sequences under certain conditions have the potential to fold into non-B DNA
      structures such as hairpin, triplex, cruciform, left-handed Z-form, tetraplex, A
      motif, etc. Since the non-B DNA-forming sequences induce the genetic instability
      and consequently can cause human diseases, the molecular mechanism for their
      genetic instability has been extensively investigated. On the contrary, non-B DNA
      can be widely used for application in biotechnology because many DNA breakage
      hotspots are mapped in or near the sequences that have the potential to adopt non
      B DNA structures. In addition, they are regarded as a fascinating material for
      the nanotechnology using non-B DNAs because they do not produce any toxic
      byproducts and are robust enough for the repetitive working cycle. This being the
      case, an understanding on the mechanism and dynamics of their structural changes
      is important. In this critical review, we describe the latest studies on the
      conformational dynamics of non-B DNAs, with a focus on G-quadruplex, i-motif, Z
      DNA, A-motif, hairpin and triplex (189 references).

PMID- 21901193
TI  - Dynamic rewiring of the androgen receptor protein interaction network correlates
      with prostate cancer clinical outcomes.
AB  - The androgen receptor (AR) is a ligand-inducible transcription factor, a member
      of the nuclear receptor superfamily, which plays an important role in the
      development and progression of prostate cancer (CaP). The transformation to CaP
      has been linked to several somatic AR gene mutations and changes in AR protein
      complex formation, which in turn increase the potential activity of the receptor.
      Thus, to address the mechanism of AR-mediated neoplastic transformation, we
      developed in vitro methodology to isolate and characterize, via mass
      spectrometry, AR complexes of three AR genetic variants: wild type-AR, and two
      somatic gain-of-function AR prostatic mutants (T877A-AR and 0CAG-AR isoforms). To
      fully characterize the significance of our large raw data set, we employed a
      sophisticated systems biology approach to create an integrative protein
      interaction network profile for each AR isoform. Our comparative analysis
      identified subnetwork cluster profiles for AR isoforms (WT, T877A, and 0CAG) that
      segregated AR isoforms on the basis of androgen stimulation conditions and mutant
      aggressiveness. Furthermore, results from additional correlative gene microarray
      analysis studies of all three AR isoform (WT, T877A, 0CAG) subnetwork clusters
      were assessed and found to be significantly enriched in tumor versus normal
      prostate tissues. We also identified two AR-interaction clusters, containing 21
      and 30 proteins, respectively, that showed unfavourable prognosis outcome of
      recurrent cancers, on the basis of PSA, Gleason score and combined PSA/Gleason
      score. In conclusion, we have characterized a large panel of novel AR-interacting
      proteins, through a combined proteomics/systems biology screen, that are of
      clinical relevance and could potentially serve as novel markers for diagnosis and
      prognosis of CaP.

PMID- 21901194
TI  - Large-scale plasmonic microarrays for label-free high-throughput screening.
AB  - Microarrays allowing simultaneous analysis of thousands of parameters can
      significantly accelerate screening of large libraries of pharmaceutical compounds
      and biomolecular interactions. For large-scale studies on diverse biomedical
      samples, reliable, label-free, and high-content microarrays are needed. In this
      work, using large-area plasmonic nanohole arrays, we demonstrate for the first
      time a large-scale label-free microarray technology with over one million sensors
      on a single microscope slide. A dual-color filter imaging method is introduced to
      dramatically increase the accuracy, reliability, and signal-to-noise ratio of the
      sensors in a highly multiplexed manner. We used our technology to quantitatively
      measure protein-protein interactions. Our platform, which is highly compatible
      with the current microarray scanning systems can enable a powerful screening
      technology and facilitate diagnosis and treatment of diseases.

PMID- 21901195
TI  - A DFT investigation of the potential of porous cages for the catalysis of ammonia
      borane dehydrogenation.
AB  - Full DFT based quantum mechanical studies reveal that zero dimensional porous
      structures, especially the newly proposed phosphorus incorporated organic cages,
      can be excellent catalysts for the dehydrogenation of ammonia borane.

PMID- 21901196
TI  - The origin of regio- and enantioselectivity in the Rh/chiral 1,4-diene-catalyzed
      addition of phenylboronic acid to enones: insights from DFT.
AB  - A density functional theory study of the addition of phenylboronic acid to
      cyclohexenone catalyzed by chiral 1,4-diene-Rh(I) catalyst reveals that 1,4
      addition is thermodynamically preferred. The enthalpy-driven enantioselection
      occurs during the carborhodation step and not the enone binding step, as
      previously proposed. The chiral ligand selectively destabilizes the disfavored
      transition state by making it "more early".

PMID- 21901197
TI  - Turning a riboflavin-binding protein into a self-sufficient monooxygenase by
      cofactor redesign.
AB  - By cofactor redesign, self-sufficient monooxygenases could be prepared. Tight
      binding of N-alkylated flavins to riboflavin-binding protein results in the
      creation of artificial flavoenzymes capable of H(2)O(2)-driven enantioselective
      sulfoxidations. By altering the flavin structure, opposite enantioselectivities
      could be achieved, in accordance with the binding mode predicted by in silico
      flavin-protein docking of the unnatural flavin cofactors. The study shows that
      cofactor redesign is a viable approach to create artificial flavoenzymes with
      unprecedented activities.

PMID- 21901198
TI  - Blooming of confused porphyrinoids--fusion, expansion, contraction, and more
      confusion.
AB  - This article introduces an overview of progressively developing chemistry of N
      confused porphyrin and related macrocycles. Study on confusion results in
      discovery of fusion and combination with expansion or contraction has provided
      uniquely important classes of porphyrinoids. Syntheses, properties and
      coordination chemistry of such porphyrinoids are briefly described. Possibilities
      in applications are also mentioned.

PMID- 21901199
TI  - A gold(I)-catalyzed intramolecular oxidation-cyclopropanation sequence of 1,6
      enynes: a convenient access to [n.1.0]bicycloalkanes.
AB  - A gold(I)-catalyzed tandem oxidation/cyclopropanation reaction of 1,6-enynes with
      an external oxidant has been developed. This quite simple and rapid strategy will
      provide a safe, mild and versatile avenue to numerous carbo- and hetero
      [n.1.0]bicyclic frameworks.

PMID- 21901200
TI  - Lightly doping Ca2+ in perovskite PrCoO3 for tailored spin states and electrical
      properties.
AB  - A series of Pr(1-x)Ca(x)CoO(3) samples were prepared using a novel molten salt
      reaction that is convenient to obtain single phases avoiding aggregates compared
      to conventional solid state reactions. The formation reaction was monitored by X
      ray diffraction combined with thermal analysis, and all samples were
      characterized by X-ray diffraction, scanning electron microscopy, Fourier
      transform infrared spectroscopy, and alternating current impedance. It is
      demonstrated that all Pr(1-x)Ca(x)CoO(3) samples crystallized in a pure
      orthorhombic perovskite structure. By increasing the doping level, the symmetry
      of the orthorhombic structure was enhanced, and is followed by an increase in the
      population of Co(3+) in the intermediate spin state. All samples exhibited
      typical semiconducting behavior, showing conductivities highly dependent on the
      Ca(2+) doping. The conduction for x = 0 shows a simple thermal activated process,
      which changed into a Mott's variable range hopping mechanism for x > 0. By
      increasing the Ca(2+) doping level, the relevant activation energy is decreased,
      while the density of the localized electronic state is increased.

PMID- 21901201
TI  - Long-range interactions between ultracold atoms and molecules including atomic
      spin-orbit.
AB  - We investigate theoretically the long-range electrostatic interactions between a
      ground-state homonuclear alkali-metal dimer and an excited alkali-metal atom
      taking into account its fine-structure. The interaction involves the combination
      of first-order quadrupole-quadrupole and second-order dipole-dipole effects.
      Depending on the considered species, the atomic spin-orbit may be comparable to
      the atom-molecule electrostatic energy and to the dimer rotational structure.
      Here we extend our general description in the framework of the second-order
      degenerate perturbation theory [M. Lepers and O. Dulieu, Eur. Phys. J. D, 2011]
      to various regimes induced by the magnitude of the atomic spin-orbit. A complex
      dynamics of the atom-molecule may take place at large distances, which may have
      consequences for the search for an universal model of ultracold inelastic
      collisions as proposed for instance in the study of Z. Idziaszek and P. S.
      Julienne [Phys. Rev. Lett.104, 2010, 113202].

PMID- 21901202
TI  - Quantum-chemical predictions of redox potentials of carbamates in methanol.
AB  - Redox potentials for two stepwise anodic oxidations of a series of carbamates in
      methanolic solution have been calculated using ab initio and DFT quantum
      mechanical methods. Hartree-Fock method and Density Functional Theory at the
      B3LYP level, together with 6-31G(d), 6-31G(d,p) and 6-311++G(2df,2p) basis sets
      have been used for the calculation. The Polarizable Continuum Model (PCM) is used
      to describe the solute-solvent interactions of carbamates, and those of their
      radical-cations and cations. Linear relationships were observed between the
      theoretically predicted redox potential values and the corresponding anodic peak
      potentials obtained by cyclic voltammetry or the corresponding calculated
      energies of the Highest Occupied Molecular Orbital (HOMO) of these carbamates.

PMID- 21901203
TI  - Role of aromaticity and charge of a system in its hydrogen trapping potential and
      vice versa.
AB  - Hydrogen storage capacity of some Li(+)/F(-) doped neutral and charged
      aromatic/antiaromatic systems is studied at the B3LYP, M05-2X, MPW1K and MP2
      levels of theory. Various conceptual density functional theory based global and
      local reactivity descriptors, nucleus independent chemical shift (NICS), NICS
      rate, interaction energy per H(2) molecule, reaction enthalpy and reaction
      electrophilicity are used for this purpose. It is observed that there is a direct
      bearing of the hydrogen adsorption capability on the aromaticity and/or the
      charge of the system (or the charge on a specific center). The latter quantities
      do also change on gradual hydrogen loading.

PMID- 21901204
TI  - Evidence of zinc superoxide formation in the gas phase: comparisons in behaviour
      between ligated Zn(I/II) and Cu(I/II) with regard to the attachment of O2 or H2O.
AB  - Singly and doubly charged atomic ions of zinc and copper have been complexed with
      pyridine and held in an ion trap. Complexes involving Zn(II) and Cu(I) (3d(10))
      display a strong tendency to bind with H(2)O, whilst the Zn(I) (3d(10)4s(1))
      complexes exhibit a strong preference for the attachment of O(2). DFT
      calculations show that this latter result can be interpreted as internal
      oxidation leading to the formation of superoxide complexes, [Zn(II)O(2)(
      )](pyridine)(n), in the gas phase. The calculations also show that the oxidation
      of Zn(I) to form Zn(II)O(2)(-) is promoted by a mixing of the occupied 4s and
      vacant 4p orbitals on the metal cation, and that this process is facilitated by
      the presence of the pyridine ligands.

PMID- 21901205
TI  - Inhibiting copper(I) iodide aggregate assembly in the solid state via macrocyclic
      encapsulation.
AB  - Three CuI complexes of diimine-bearing macrocyclic ligands are described.
      Reaction of CuI with macrocycles of different ring size gives rise to differing
      degrees of aggregation of (CuI)(n) in the solid state. X-Ray diffraction studies
      reveal that whereas macrocycles with smaller ring sizes give rise to simple
      mononuclear CuI diimine complexes, a macrocycle of larger ring size affords a
      dinuclear (CuI)(2) moiety, encompassed within the ligand ring. Thus, the
      macrocycle can be seen to determine the extent of CuI aggregation in the solid
      state.

PMID- 21901206
TI  - Voltage-expandable liquid crystal surface.
AB  - Based on dielectrophoretic effect, we report a novel approach which can
      extensively spread a liquid crystal (LC) interface. With interdigitated striped
      electrodes, the droplets can be stretched along the striped electrode direction;
      while with zigzag interdigitated electrodes, the droplets can be further
      stretched sidewise. In our demonstration, the occupied area of a 1.9-mm-aperture
      LC droplet doped with 1.2 wt% black dye could be expanded over ~3.5* at 78
      V(rms). The spreading and recovering times were measured to be ~0.39 s and ~0.75
      s, respectively. The slower response time confirms the extreme expanding of the
      LC surface. The contrast ratio is over ~120 : 1 in transmissive mode. Color light
      switch was also demonstrated by spreading colored-dye doped LC droplets. The
      mechanical stability of the device was also evaluated. Liquid devices based on
      this cell structure have the advantages of good stability, simple operation and
      low power consumption. This work opens a new gateway for voltage controllable,
      polarization-insensitive, and broadband liquid photonic devices which may find
      numerous applications in switchable windows, variable optical attenuators, and
      displays.

PMID- 21901207
TI  - A switchable digital microfluidic droplet dye-laser.
AB  - Digital microfluidic devices allow the manipulation of droplets between two
      parallel electrodes. These electrodes can act as mirrors generating a micro
      cavity, which can be exploited for a droplet dye-laser. Three representative
      laser-dyes with emission wavelengths spanning the whole visible spectrum are
      chosen to show the applicability of this concept. Sub-microlitre droplets of
      laser-dye solution are moved in and out of a lasing site on-chip to down-convert
      the UV-excitation light into blue, green and red laser-pulses.

PMID- 21901208
TI  - Linking biological activity with herbal constituents by systems biology-based
      approaches: effects of Panax ginseng in type 2 diabetic Goto-Kakizaki rats.
AB  - Although a number of animal experiments and clinical trials have investigated the
      effects of ginseng roots on diabetes, the relationship between their therapeutic
      effects on diabetes and the quality and the growth age of this herb have not yet
      been reported. This study systematically investigated the effects of 3- to 6-year
      old ginseng roots on glycemic and plasma lipid control in a rat model of type 2
      diabetes. Six groups of male Goto-Kakizaki (GK) rats received either metformin, 3
      to 6-year-old ginseng roots, or no treatment. The treatments were administered
      twice daily for 9 weeks. A combined approach was used that involved applying
      liquid chromatography-mass spectrometry-based lipidomics, measuring biochemical
      parameters and profiling the components of ginseng roots of different ages.
      Compared to the untreated controls, treatment with 4- and 6-year-old ginseng
      roots significantly improved glucose disposal, and 5-year-old ginseng treatment
      significantly increased high density lipoprotein cholesterol. Treatment with 6
      year-old ginseng significantly decreased total plasma triacylglyceride (TG) and
      very-low-density lipoprotein cholesterol and improved plasma glycated hemoglobin
      (HbA1c). In addition, treatment with 4- to 6-year-old ginseng influenced plasma
      lipidomics in diabetic GK rats by reducing TG lipid species. Metformin
      significantly reduced fasting blood glucose by 41% and reduced HbA1c by 11%, but
      showed no effects on the plasma lipid parameters. The present study demonstrates
      that ginseng roots show growth age-dependent therapeutic effects on
      hyperlipidemia and hyperglycemia in diabetic GK rats. These age-dependent effects
      may be linked with the variation in both the ratios and concentrations of
      specific bioactive ginsenosides in ginseng roots of different growth ages. This
      study introduced novel systems biology-based approaches for linking biological
      activities with potential active components in herbal mixtures.

PMID- 21901209
TI  - Disorders associated with systemic or local iron overload: from pathophysiology
      to clinical practice.
AB  - In healthy subjects, the rate of dietary iron absorption, as well as the amount
      and distribution of body iron are tightly controlled by hepcidin, the iron
      regulatory hormone. Disruption of systemic iron homeostasis leads to pathological
      conditions, ranging from anemias caused by iron deficiency or defective iron
      traffic, to iron overload (hemochromatosis). Other iron-related disorders are
      caused by misregulation of cellular iron metabolism, which results in local
      accumulation of the metal in mitochondria. Brain iron overload is observed in
      neurodegenerative disorders. Secondary hemochromatosis develops as a complication
      of another disease. For example, repeated blood transfusions, a standard
      treatment of various anemias characterized by ineffective erythropoiesis, promote
      transfusional siderosis, while chronic liver diseases are often associated with
      mild to moderate secondary iron overload. In this critical review, we discuss
      pathophysiological and clinical aspects of all types of iron metabolism disorders
      (265 references).

PMID- 21901210
TI  - Light-emitting nanocomposite CdS-polymer electrospun fibres via in situ
      nanoparticle generation.
AB  - We report on the simple, in situ generation of CdS nanocrystals inside
      electrospun polymer fibres by thermal decomposition of a cadmium thiolate
      precursor, leading to nanocomposite light-emitting fibres. The modifications
      induced in the precursor by the thermal decomposition are investigated by a
      morphological, structural and spectroscopic analysis of the resulting
      nanocomposite fibres. This approach allows us to overcome nanofabrication
      difficulties related to disfavoured micro- or nanofluidic molecular flow as given
      by the direct incorporation of particles in the electrospinning solution. This
      method therefore enables the synthesis of luminescent, CdS-based composite fibres
      with emission peaked in the visible range, suitable as building blocks for
      nanophotonic devices based on light-emitting nanomaterials.

PMID- 21901211
TI  - Macromolecular nanotheranostics for multimodal anticancer therapy.
AB  - Macromolecular carrier materials based on N-(2-hydroxypropyl)methacrylamide
      (HPMA) are prototypic and well-characterized drug delivery systems that have been
      extensively evaluated in the past two decades, both at the preclinical and at the
      clinical level. Using several different imaging agents and techniques, HPMA
      copolymers have been shown to circulate for prolonged periods of time, and to
      accumulate in tumors both effectively and selectively by means of the Enhanced
      Permeability and Retention (EPR) effect. Because of this, HPMA-based
      macromolecular nanotheranostics, i.e. formulations containing both drug and
      imaging agents within a single formulation, have been shown to be highly
      effective in inducing tumor growth inhibition in animal models. In patients,
      however, as essentially all other tumor-targeted nanomedicines, they are
      generally only able to improve the therapeutic index of the attached active agent
      by lowering its toxicity, and they fail to improve the efficacy of the
      intervention. Bearing this in mind, we have recently reasoned that because of
      their biocompatibility and their beneficial biodistribution, nanomedicine
      formulations might be highly suitable systems for combination therapies. In the
      present manuscript, we briefly summarize several exemplary efforts undertaken in
      this regard in our labs in the past couple of years, and we show that long
      circulating and passively tumor-targeted macromolecular nanotheranostics can be
      used to improve the efficacy of radiochemotherapy and of chemotherapy
      combinations.

PMID- 21901212
TI  - DNA damage spectra induced by photosensitization.
AB  - DNA damage induced by photosensitization is not only responsible for the
      genotoxic effects of various types of drugs in the presence of light, but is also
      relevant for some of the adverse effects of sunlight, in particular in the UVA
      and visible range of the spectrum. The types of DNA modifications induced are
      very diverse and include pyrimidine dimers, covalent adducts, various base
      modifications generated by oxidation, single-strand breaks and (regular and
      oxidized) sites of base loss. The ratios in which the various modifications are
      formed (damage spectra) can be regarded as a fingerprint of the damaging
      mechanism. Here, we describe the damage spectra of various classes of
      photosensitizers in relation to the underlying damaging mechanisms. In mammalian
      cells irradiated with solar radiation, damage at wavelengths <400 nm is
      characteristic for a (not yet identified) endogenous type-I or type-II
      photosensitizer. In the UVA range, however, both direct DNA excitation and
      photosensitized damage appear to be relevant, and there are indications that
      other chromophore(s) are involved than in the visible range.

PMID- 21901213
TI  - A non-enzymatic sensor for hydrogen peroxide based on polyaniline, multiwalled
      carbon nanotubes and gold nanoparticles modified Au electrode.
AB  - We describe the construction of a polyaniline (PANI), multiwalled carbon
      nanotubes (MWCNTs) and gold nanoparticles (AuNPs) modified Au electrode for
      determination of hydrogen peroxide without using peroxidase (HRP). The
      AuNPs/MWCNT/PANI composite film deposited on Au electrode was characterized by
      Scanning Electron Microscopy (SEM) and electrochemical methods. Cyclic
      voltammetric (CV) studies of the electrode at different stages of construction
      demonstrated that the modified electrode had enhanced electrochemical oxidation
      of H(2)O(2), which offers a number of attractive features to develop amperometric
      sensors based on split of H(2)O(2). The amperometric response to H(2)O(2) showed
      a linear relationship in the range from 3.0 MUM to 600.0 MUM with a detection
      limit of 0.3 MUM (S/N = 3) and with high sensitivity of 3.3 mA MUM(-1). The
      sensor gave accurate and satisfactory results, when employed for determination of
      H(2)O(2) in milk and urine.

PMID- 21901214
TI  - Determination of concentration and enantiomeric excess of amines and amino
      alcohols with a chiral nickel(II) complex.
AB  - A chiral N,N'-dioxide-Ni(II) complex was found to exhibit highly enantioselective
      fluorescent recognition of chiral amines and amino alcohols. It can be used to
      determine their concentration and ee value. Using a 96-well plate, high
      throughput screening for enantiomer discrimination was accomplished.

PMID- 21901215
TI  - 1-Borabenzonitrile (B-cyanoboratabenzene).
AB  - The reaction of 1-chloro-2-(trimethylsilyl)-1-boracyclohexa-2,5-diene with
      [(n)Bu(4)N]C=N provides the 1-borabenzonitrile salt [(n)Bu(4)N][C(5)H(5)BC=N]
      which in turn reacts with [Ru(4)(MU-Cl)(4)(eta-C(5)Me(5))(4)] to afford the
      sandwich complex [Ru(eta(6)-C(5)H(5)BC=N)(eta-C(5)Me(5))]. The bonding of 1
      borabenzonitrile is discussed with recourse to crystallographic data for
      [(n)Bu(4)N][C(5)H(5)BC=N] and [Ru(eta(6)-C(5)H(5)BC=N)(eta-C(5)Me(5))].

PMID- 21901216
TI  - Long-range linear elasticity and mechanical instability of self-scrolling
      binormal nanohelices under a uniaxial load.
AB  - Mechanical properties of self-scrolling binormal nanohelices with a rectangular
      cross-section are investigated under uniaxial tensile and compressive loads using
      nanorobotic manipulation and Cosserat curve theory. Stretching experiments
      demonstrate that small-pitch nanohelices have an exceptionally large linear
      elasticity region and excellent mechanical stability, which are attributed to
      their structural flexibility based on an analytical model. In comparison between
      helices with a circular, square and rectangular cross-section, modeling results
      indicate that, while the binormal helical structure is stretched with a large
      strain, the stress on the material remains low. This is of particular
      significance for such applications as elastic components in micro
      /nanoelectromechanical systems (MEMS/NEMS). The mechanical instability of a self
      scrolling nanohelix under compressive load is also investigated, and the low
      critical load for buckling suggests that the self-scrolling nanohelices are more
      suitable for extension springs in MEMS/NEMS.

PMID- 21901217
TI  - Unravelling UVA-induced mutagenesis.
AB  - Ultraviolet A (UVA) radiation represents more than 90% of the solar UV radiation
      reaching Earth's surface. Exposure to solar UV radiation is a major risk in the
      occurrence of non-melanoma skin cancer. Whole genome sequencing data of melanoma
      tumors recently obtained makes it possible also to definitively associate
      malignant melanoma with sunlight exposure. Even though UVB has long been
      established as the major cause of skin cancer, the relative contribution of UVA
      is still unclear. In this review, we first report on the formation of DNA damage
      induced by UVA radiation, and on recent advances on the associated mechanism. We
      then discuss the controversial data on the UVA-induced mutational events obtained
      for various types of eukaryotic cells, including human skin cells. This may help
      unravel the role of UVA in the various steps of photocarcinogenesis. The
      connection to photocarcinogenesis is more extensively discussed by other authors
      in this issue.

PMID- 21901218
TI  - Enzymatic methods for glyco(diversification/randomization) of drugs and small
      molecules.
AB  - Glyco (randomization/diversification) is a term that encompasses strategies to
      diversify a core drug scaffold via enzymatic glycosylation to provide sets of
      analogs wherein the sole diversity element is a carbohydrate. This review covers
      the influence of glycosylation upon various drug properties, the classes of
      glycosyl-conjugating enzymes amenable to glyco(randomization/diversification)
      schemes, approaches to the synthesis of required substrates and specific examples
      of glycorandomized libraries utilizing both wild-type and engineered enzymes.

PMID- 21901219
TI  - A 'chemically-gated' photoresponsive compound as a visible detector for
      organophosphorus nerve agents.
AB  - We describe a versatile and convenient visible detection method for
      organophosphorus compounds based on a colorless 'pro-photoresponsive' organic
      molecule that undergoes photochemical ring-closing to produce a colored isomer
      only after it reacts with vapors of the phosphorylating agent.

PMID- 21901220
TI  - Oxidation of 10-undecenoic acid by cytochrome P450(BM-3) and its Compound I
      transient.
AB  - Oxidations of 10-undecenoic acid by cytochrome P450(BM-3) and its Compound I
      transient were studied. The only product formed in Compound I oxidations was
      10,11-epoxyundecanoic acid, whereas the enzyme under turnover conditions gave the
      epoxide and 9-hydroxy-10-undecenoic acid in a 10 : 90 ratio. Kinetic studies at 0
      degrees C of oxidations by Compounds I formed by MCPBA oxidation and by a photo
      oxidation pathway gave the same results, displaying saturation kinetics that
      yielded equilibrium binding constants and first-order oxidation rate constants
      that were experimentally indistinguishable. Oxidation of 10-undecenoic acid by
      Compound I from CYP119 generated by MCBPA oxidation also gave 10,11
      epoxyundecanoic acid as the only product. CYP119 Compound I bound the substrate
      less strongly but reacted with a faster oxidation rate constant than P450(BM-3)
      Compound I. The kinetic parameters for oxidation of the substrate by P450(BM-3)
      under turnover conditions were similar to those of the Compound I transient even
      though the products differed.

PMID- 21901221
TI  - Novel synthetic baicalein derivatives caused apoptosis and activated AMP
      activated protein kinase in human tumor cells.
AB  - Studies on the anti-proliferative activities of novel baicalein derivatives
      demonstrated that compounds 8 and 9 were able to activate AMPK by enhancing the
      levels of phosphorylated AMPKalpha, and showed more potent anti-proliferative
      effects than baicalein and AICAR in A431, SK-OV-3, DU 145 and HeLa cells,
      suggesting an alternative therapeutic approach for benzyl baicalein in cancer
      therapy.

PMID- 21901222
TI  - Cytosine-phosphodiester-guanine oligodeoxynucleotide (CpG ODN)-capped hollow
      mesoporous silica particles for enzyme-triggered drug delivery.
AB  - We designed, for the first time, an enzyme-triggered drug delivery system that is
      based on cytosine-phosphodiester-guanine oligodeoxynucleotide (CpG ODN)-capped
      hollow mesoporous silica (HMS) particles as carriers. Fluorescein dye was used as
      a model drug, and the fluorescein loading, amino-grafting and CpG ODN capping
      were evaluated by UV/Vis analysis, zeta potential and N(2) adsorption-desorption
      measurements and gel electrophoresis. The fluorescein loading capacity and CpG
      ODN capping amount were 37.7 and 39.6 MUg mg(-1), respectively at the weight
      ratio of 10 Dye/HMS-NH(2)/CpG ODN. Importantly, fluorescein release can be
      triggered by the addition of deoxyribonuclease I (DNase I) for CpG ODN
      degradation, and the release rate can also be controlled by changing the DNase I
      concentration. Therefore, it might be a promising controlled drug delivery system
      for application in the field of biomedicine and cancer therapy.

PMID- 21901223
TI  - Modeling the interactions between peptide functions and Sr2+: formamide-Sr2+
      reactions in the gas phase.
AB  - The interactions between formamide, which can be considered a prototype of a
      peptide function, and Sr(2+) have been investigated by combining nanoelectrospray
      ionization/mass spectrometry techniques and G96LYP DFT calculations. For Sr an
      extended LANL2DZ basis set was employed, together with a 6-311+G(3df,2p) basis
      set expansion for the remaining atoms of the system. The observed reactivity
      seems to be dominated by the Coulomb explosion process yielding [SrOH](+) +
      [HNCH](+), which are the most intense peaks in the MS/MS spectra. Nevertheless,
      additional peaks corresponding to the loss of HNC and CO indicate that the
      association of Sr(2+) to water or to ammonia leads to long-lived doubly charged
      species detectable in the timescale of these experimental techniques. The
      topology of the calculated potential energy surface permits us to establish the
      mechanisms behind these processes. Although the interaction between the neutral
      base and Sr(2+) is essentially electrostatic, the polarization triggered by the
      doubly charged metal ion results in the activation of several bonds, and favors
      different proton transfer mechanisms required for the formation of the [SrOH](+),
      [SrOH(2)](2+) and [SrNH(3)](2+) products.

PMID- 21901224
TI  - Unique Pt5 metallacycle: [Pt(II)Cl(pyrrolidinedithiocarbamate)]5.
AB  - The neutral complex [PtCl(PyDT)](5) (PyDT = (CH(2))(4)NCS(2)(-)) represents the
      first example of a Pt(5) metallacycle. This unique architecture based on chiral S
      bridged Pt(II) monomers was prepared by thermal degradation of the reaction
      product of PtCl(2) and a pyrrolidinedithioester.

PMID- 21901225
TI  - Enhanced nanoflow behaviors of polymer melts using dispersed nanoparticles and
      ultrasonic vibration.
AB  - In the micro/nano fabrication of polymer nanostructures, a key factor is the
      favorable nanoflow behavior of polymer melts. Compared with the fluidic
      hydrodynamics of simple liquids through micro- or macrochannels, the nanoflow
      behavior of polymer melts, however, is affected much more by nanoscale effects
      and surface interactions. Therefore, achieving a favorable nanoflow of polymer
      melts in nanochannels is the key to fabricate high quality polymer nanoproducts.
      In this paper, the improved nanoflow behaviors of polystyrene melts in ordered
      porous alumina templates with the addition of nanoparticles and ultrasonic
      vibration were reported for the first time. Compared with bulk polystyrene (PS),
      the nanoflow rate of PS melts was enhanced when nanoparticles, such as surface
      modified nano-silica (nano-SiO(2)) or beta-cyclodextrin (beta-CD), were added in
      a dispersed phase into a polystyrene matrix due to the decrease of the melts'
      viscosity caused by interactions between nanoparticles and PS segments. The
      enhancement action of beta-CD was observed to be more significant than that of
      nano-SiO(2) based on the adsorption and the supramolecular self-assembly
      interactions between PS segments and beta-CD. The enhanced nanoflow rate has
      shown to be more pronounced under ultrasonic vibration than those of the static
      condition and the low frequency vibration attributed to the synergetic effects of
      mechanical vibration and ultrasonic oscillation. The nanoflow rate of polymer
      melts increases with the gradual increase of vibration frequency. The optimal
      nanoflow behavior can be obtained by simultaneously adding beta-CD as dispersed
      phase into PS matrix and applying ultrasonic vibration in one nanoflow system.
      These new findings will help the preparation of polymer-based functional
      nanocomposites, ultrasonic vibration-assisted nanofluidics, and micro/nano
      injection molding etc.

PMID- 21901227
TI  - Prothrombin complex concentrate reduces blood loss and enhances thrombin
      generation in a pig model with blunt liver injury under severe hypothermia.
AB  - Although prothrombin complex concentrate (PCC) is increasingly used for the
      treatment of trauma-induced coagulopathy, few studies have investigated the
      impact and safety of PCC for this indication. The present study was performed to
      assess PCC for treatment of coagulopathy after blunt liver injury under severe
      hypothermia. Coagulopathy in 14 anaesthetised pigs was induced by haemodilution.
      Subsequently, standardised blunt liver injury was induced under severe
      hypothermia (32.8-33.2 degrees C). Animals were randomised to receive either PCC
      (35 IU kg-1) or saline (control). Coagulation was assessed over the following 2
      hours by thromboelastometry and thrombin generation. Internal organs were
      examined to determine presence of emboli. The administration of PCC showed a
      significant reduction in blood loss (p=0.002 vs. controls) and a significant
      increase in the rate of survival (p=0.022 vs. controls). Plasma thrombin
      generation in the PCC group increased considerably above baseline levels, with
      significant increases in peak thrombin levels and endogenous thrombin potential
      versus controls throughout the follow-up period. In addition, PT decreased
      significantly in the PCC group versus the control group. However, only slight
      improvements in thromboelastometry variables were observed. Histology showed an
      equal degree of liver injury in both groups, and no thromboembolism. In severely
      hypothermic pigs, the application of PCC corrected trauma-induced coagulopathy
      and reduced blood loss. Thus, the infusion of PCC might be a reasonable approach
      to reduce the need for blood cell transfusion in trauma. Furthermore, the impact
      and safety of PCC application can be monitored through thrombin generation and
      thromboelastometry under hypothermia.

PMID- 21901228
TI  - Endothelial glycocalyx thickness and platelet-vessel wall interactions during
      atherogenesis.
AB  - The endothelial glycocalyx (EG), the luminal cover of endothelial cells, is
      considered to be atheroprotective. During atherogenesis, platelets adhere to the
      vessel wall, possibly triggered by simultaneous EG modulation. It was the
      objective of this study to investigate both EG thickness and platelet-vessel wall
      interactions during atherogenesis in the same experimental model. Intravital
      fluorescence microscopy was used to study platelet-vessel wall interactions  in
      vivo  in common carotid arteries and bifurcations of C57bl6/J (B6) and
      apolipoprotein E knock-out (ApoE-/-) mice (age 7 - 31 weeks). At the same
      locations, EG thickness was determined  ex vivo  using two-photon laser scanning
      microscopy. In ApoE-/- bifurcations the overall median level of adhesion was 48
      platelets/mm2 (interquartile range: 16 - 80), which was significantly higher than
      in B6 bifurcations (0 (0 - 16), p = 0.001). This difference appeared to result
      from a significant age-dependent increase in ApoE-/- mice, while no such change
      was observed in B6 mice. At the same time, the EG in ApoE-/- bifurcations was
      significantly thinner than in B6 bifurcations (2.2 vs. 2.5 MUm, respectively; p <
      0.05). This resulted from the fact that in B6 bifurcations EG thickness increased
      with age (from 2.4 MUm in young mice to 3.0 um in aged ones), while in
      bifurcations of ApoE-/- mice this growth appeared to be absent (2.2 MUm at all
      ages). During atherogenesis, platelet adhesion to the wall of the carotid artery
      bifurcation increases significantly. At the same location, EG growth with age is
      hampered. Therefore, glycocalyx-reinforcing strategies could possibly ameliorate
      atherosclerosis.

PMID- 21901226
TI  - A systematic overview of prospective cohort studies of cardiovascular disease in
      sub-Saharan Africa.
AB  - BACKGROUND: Cardiovascular diseases (CVDs) are becoming increasingly significant
      in sub-Saharan Africa (SSA). Reliable measures of the contribution of major
      determinants are essential for informing health services and policy solutions.
      OBJECTIVE: To perform a systematic review of all longitudinal studies of CVDs and
      related risk factors that have been conducted in SSA. DATA SOURCE: We searched
      electronic databases from 1966 to October 2009. Published studies were retrieved
      from PubMed and Africa EBSCO. Reference lists of identified articles were scanned
      for additional publications. STUDY SELECTION: Any longitudinal study with data
      collection at baseline on major cardiovascular risk factors or CVD, including 30
      or more participants, and with at least six months of follow up were included.
      DATA EXTRACTION: Data were extracted on the country of study, year of inception,
      baseline evaluation, primary focus of the study, outcomes, and number of
      participants at baseline and final evaluation. RESULTS: Eighty-one publications
      relating to 41 studies from 11 SSA countries with a wide range of participants
      were included. Twenty-two were  historical/prospective hospitalbased studies.
      These studies focused on risk factors, particularly diabetes mellitus and
      hypertension, or CVD including stroke, heart failure and rheumatic heart disease.
      The rate of participants followed through the whole duration of studies was 72%
      (64-80%), with a significant heterogeneity between studies (for heterogeneity, p
      < 0.001). Outcomes monitored during follow up included trajectories of risk
      markers and mortality. CONCLUSIONS: Well-designed prospective cohort studies are
      needed to inform and update our knowledge regarding the epidemiology CVDs and
      their interactions with known risk factors in the context of common infectious
      diseases in this region.

PMID- 21901230
TI  - Involvement of IRAKs and TRAFs in anti-beta2GPI/beta2GPI-induced tissue factor
      expression in THP-1 cells.
AB  - Our previous study has shown that Toll-like receptor 4 (TLR4) and its signalling
      pathway contribute to anti-beta2-glycoprotein I/beta2-glycoprotein I (anti
      beta2GPI/beta2GPI)-induced tissue factor (TF) expression in human acute monocytic
      leukaemia cell line THP-1 and annexin A2 (ANX2) is involved in this pathway.
      However, its downstream molecules have not been well explored. In this study, we
      have established that interleukin-1 receptor-associated kinases (IRAKs) and
      tumour necrosis factor receptor-associated factors (TRAFs) are crucial downstream
      molecules of anti-beta2GPI/beta2GPI-induced TLR4 signaling pathway in THP-1 cells
      and explored the potential mechanisms of their self-regulation. Treatment of THP
      1 cells with anti-beta2GPI/beta2GPI complex induced IRAKs and TRAFs expression
      and activation. Anti-beta2GPI/beta2GPI complex firstly induced expression of
      IRAK4 and IRAK1, then IRAK1 phosphorylation and last IRAK3 upregulation. In
      addition, anti-beta2GPI/beta2GPI complex simultaneously and acutely enhanced mRNA
      levels of TRAF6, TRAF4 and zinc finger protein A20 (A20), while chronically
      increased A20 protein level. Moreover, anti-beta2GPI/beta2GPI complex-induced
      IRAKs and TRAFs expression and activation were attenuated by knockdown of ANX2 by
      infection with ANX2-specific RNA interference lentiviruses (LV-RNAi-ANX2) or by
      treatment with paclitaxel, which inhibits TLR4 as an antagonist of myeloid
      differentiation protein 2 (MD-2) ligand. Furthermore, both IRAK1/4 inhibitor and
      a specific proteasome inhibitor MG-132 could attenuate TRAFs expression as well
      as TF expression induced by anti-beta2GPI/beta2GPI complex. In conclusion, our
      results indicate that IRAKs and TRAFs play important roles in anti
      beta2GPI/beta2GPI-stimulated TLR4/TF signaling pathway in THP-1 cells and
      contribute to the pathological processes of antiphospholipid syndrome (APS).

PMID- 21901231
TI  - Common variants in the haemostatic gene pathway contribute to risk of early-onset
      myocardial infarction in the Italian population.
AB  - Occlusive coronary thrombus formation superimposed on an atherosclerotic plaque
      is the ultimate event leading to myocardial infarction (MI). Therefore,
      haemostatic proteins may represent important players in the pathogenesis of MI.
      It was the objective of this study to evaluate, in a comprehensive way, the role
      of haemostatic gene polymorphisms in predisposition to premature MI. A total of
      810 single nucleotide polymorphisms (SNPs) in 37 genes were assessed for
      association with MI in a large cohort (1,670 males, 210 females) of Italian
      patients who suffered from an MI event before the age of 45, and an equal number
      of controls. Thirty-eight SNPs selected from the literature were genotyped using
      the SNPlex technology, whereas genotypes for the remaining 772 SNPs were
      extracted from a previous genome-wide association study. Genotypes were analysed
      by a standard case-control analysis corrected for classical cardiovascular risk
      factors, and by haplotype analysis. A weighted Genetic Risk Score (GRS) was
      calculated. Evidence for association with MI after covariate correction was found
      for 35 SNPs in 12 loci: F5, PROS1, F11, ITGA2, F12, F13A1, SERPINE1, PLAT, VWF,
      THBD, PROCR, and F9. The weighted GRS was constructed by including the top SNP
      for each of the 12 associated loci. The GRS distribution was significantly
      different between cases and controls, and subjects in the highest quintile had a
      2.69-fold increased risk for MI compared with those in the lowest quintile. Our
      results suggest that a GRS, based on the combined effect of several risk alleles
      in different haemostatic genes, is associated with an increased risk of MI.

PMID- 21901232
TI  - Factor VIII activation by factor VIIa analog (V158D/E296V/M298Q) in tissue factor
      independent mechanisms.
AB  - Factor (F)VIIa with tissue factor (TF) is a primary trigger of blood coagulation.
      The recombinant (r)FVIIa analog, NN1731 (V158D/E296V/ M298Q) containing a
      thrombin/FIXa-mimicking catalytic domain, is ~30-fold more effective on activated
      platelets without TF, but ~1.2-fold with TF, than rFVIIa for FX activation. We
      have recently demonstrated the FVIIa/TF-dependent FVIII activation in the early
      coagulation phase. We assessed the action of NN1731 on FVIII activation.
      NN1731/TF increased FVIII activity ~2.9-fold within 30 seconds, followed by rapid
      inactivation, and was slightly more active than rFVIIa/TF. NN1731-catalysed
      activation, however, was enhanced ~6-fold at 5 minutes (min), and its peak level
      persisted for ~30 min. NN1731/TF proteolysed FVIII at Arg740, Arg372, and Arg336,
      similar to rFVIIa/TF, but cleavage by NN1731 alone was much slower at Arg336 than
      at Arg740 and Arg372. The Km and Vmax for NN1731/TF-catalysed activation were
      ~1.8-fold lower and ~2.3-fold greater than rFVIIa/TF. The Km for NN1731 alone was
      ~1.3-fold lower than rFVIIa, whilst the Vmax was ~7.9-fold greater, indicating
      that the efficiency of FVIII activation by NN1731 and NN1731/TF was ~11- and ~4
      fold greater, respectively, than equivalent reactions with rFVIIa. In SPR-based
      assays, NN1731 bound to FVIII and the heavy chain (Kd; 0.62 and 1.9 nM) with ~1.4
      and ~3.1-fold higher affinity than rFVIIa, and the A2 domain contributed to this
      increase. Von Willebrand factor moderated NN1731-catalysed activation more
      significantly than NN1731/TF. In conclusion, NN1731 was a greater potential than
      rFVIIa in up-regulating FVIII activity, and the TF-independent FVIII activation
      might represent a potential extra mode of its enhanced haemostatic effect.

PMID- 21901229
TI  - Venous thromboembolism in patients with intracranial haemorrhage.

PMID- 21901233
TI  - Interference of rivaroxaban in one-stage and chromogenic factor VIII:C assays.

PMID- 21901234
TI  - The role of fibrinogen plasma levels, the -455G>A fibrinogen and the factor XIII
      A subunit (FXIII-A) Val34Leu polymorphism in cancer-associated venous thrombosis.
AB  - Venous thromboembolism (VTE) is a life-threatening complication in cancer
      patients. Identification of risk factors has been in focus in the past years.
      Functional single nucleotide polymorphisms (SNP) of coagulation factors known to
      influence the concentration or function may be considered to influence the risk
      of VTE in cancer patients. We evaluated the influence of fibrinogen plasma
      levels, the -455G>A SNP in the fibrinogen beta gene and the Val34Leu (163G>T) SNP
      in the factor XIII A-subunit (FXIII-A) gene on the risk of VTE. In 1,079 tumour
      patients recruited for the prospective Vienna Cancer and Thrombosis Study (CATS)
      fibrinogen levels were determined by the Clauss method. The FXIII-A Val34Leu and
      the fibrinogen -455G>A SNPs were tested by allele-specific PCR. The median follow
      up time was 604 days, 83 thrombotic events occurred. The median fibrinogen level
      was 381 mg/dl (25th-75th percentile: 312 to 467). In a multivariable Cox model
      adjusted to chemotherapy, surgery, radiotherapy, age and sex, neither the
      fibrinogen concentration (hazard ratio [HR] =1.05, confidence interval [CI] 0.839
      1.310 p=0.68), nor the -455G>A SNP (HR=0.77, 95%CI 0.491-1.197; p=0.24), nor the
      Val34Leu SNP (HR=0.99, 95%CI 0.646-1.542 p=0.99) were associated with occurrence
      of VTE. The fibrinogen concentration was not significantly different among the
      fibrinogen -455G or A genotype carriers (p = 0.33). Disseminated intravascular
      coagulation was observed in only five patients, none of these developed VTE. In
      conclusion, fibrinogen plasma levels, the fibrinogen -455G>A and the FXIII-A
      Val34Leu polymorphisms were not associated with VTE in our study.

PMID- 21901235
TI  - Dendritic cells in atherosclerosis: functions in immune regulation and beyond.
AB  - Chronic inflammation drives the development of atherosclerosis. Dendritic cells
      (DCs) are known as central mediators of adaptive immune responses and the
      development of immunological memory and tolerance. DCs are present in non
      diseased arteries, and accumulate within atherosclerotic lesions where they can
      be localised in close vicinity to  T cells. Recent work has revealed important
      functions of DCs in regulating immune mechanisms in atherogenesis, and
      vaccination strategies using DCs have been explored for treatment of disease.
      However, in line with a phenotypical and functional overlap with plaque
      macrophages vascular DCs were also identified to engulf lipids, thus contributing
      to lipid burden in the vessel wall and initiation of lesion growth. Furthermore,
      a function of DCs in regulating cholesterol homeostasis has been revealed.
      Finally, phenotypically distinct plasmacytoid dendritic cells (pDCs) have been
      identified within atherosclerotic lesions. This review will dissect the
      multifaceted contribution of DCs and pDCs to the initiation and progression of
      atherosclerosis and the experimental approaches utilising DCs in therapeutic
      vaccination strategies.

PMID- 21901236
TI  - Successful treatment with intravenous immunoglobulin (IVIg) in a patient with an
      acquired factor V inhibitor after liver transplantation.

PMID- 21901238
TI  - Bleeding diathesis in patients with mast cell activation disease.

PMID- 21901237
TI  - Novel recombinant glycosylphosphatidylinositol (GPI)-anchored ADAMTS13 and
      variants for assessment of anti-ADAMTS13 autoantibodies in patients with
      thrombotic thrombocytopenic purpura.
AB  - Immunoglobulin Gs (IgGs) against ADAMTS13 are major causes of acquired
      (idiopathic) thrombotic thrombocytopenic purpura (TTP). We report here a novel
      cell-based assay using glycosylphosphatidylinositol (GPI)-anchored ADAMTS13 or
      variants expressed on cell membrane for assessment of autoantibodies in patients
      with TTP. We showed that IgGs from all 26 patients with acquired TTP bound to
      cells expressing a GPI anchored full-length ADAMTS13 (gFL) and a variant
      truncated after the spacer domain (gS). Also, IgGs from 25/26 (96.7%) of these
      TTP patients bound to cells expressing a GPI-anchored C-terminal fragment, TSP1 2
      8 plus CUB (gT2C). In contrast, none of the 20 healthy blood donors showed
      detectable binding of their IgGs to the cells expressing gFL, gS, and gT2C. A
      moderate, but statistically significant correlation was observed between plasma
      concentrations of anti-ADAMTS13 IgG and positive cells expressing gFL (r=0.65),
      gS (r=0.67), and gT2C (r=0.42). These results suggest that the microtiter-plate
      assay and the cell-based assay may detect differential antigenic epitopes.
      Moreover, antigens clustered on cell membranes may enhance antibody binding
      affinity, thereby increasing analytical sensitivity. Finally, our assay was able
      to determine kinetic changes of plasma levels of anti-ADAMTS13 IgGs in TTP
      patients during plasma therapy. Together, our findings suggest that the novel
      cell-based assay may be applicable for rapid identification and mapping of anti
      ADAMTS13 autoantibodies in patients with acquired TTP.

PMID- 21901239
TI  - Risks of stroke and mortality associated with suboptimal anticoagulation in
      atrial fibrillation patients.
AB  - Atrial fibrillation (AF) carries an increased risk of ischaemic stroke, and oral
      anticoagulation with warfarin can reduce this risk. The objective of this study
      was to evaluate the association between time in therapeutic International
      Normalised Ratio (INR) range when receiving warfarin and the risk of stroke and
      mortality. The study cohort included AF patients aged 40 years and older included
      in the UK General Practice Research Database. For patients treated with warfarin
      we computed the percentage of follow-up time spent within therapeutic range. Cox
      regression was used to assess the association between INR and outcomes while
      controlling for patient demographics, health status and concomitant medication.
      The study population included 27,458 warfarin-treated (with at least 3 INR
      measurements) and 10,449 patients not treated with antithrombotic therapy.
      Overall the warfarin users spent 63% of their time within therapeutic range
      (TTR). This percentage did not vary substantially by age, sex and CHA2DS2-VASc
      score. Patients who spent at least 70% of time within therapeutic range had a 79%
      reduced risk of stroke compared to patients with <=30% of time in range (adjusted
      relative rate of 0.21; 95% confidence interval 0.18-0.25). Mortality rates were
      also significantly lower with at least 70% of time spent within therapeutic
      range. In conclusion, good anticoagulation control was associated with a
      reduction in the risk of stroke.

PMID- 21901240
TI  - Recombinant activated protein C attenuates coagulopathy and inflammation when
      administered early in murine pneumococcal pneumonia.
AB  - Recombinant human activated protein C (APC), which has both anticoagulant and
      anti-inflammatory properties, improves survival of patients with severe sepsis.
      This beneficial effect is especially apparent in patients with pneumococcal
      pneumonia. Earlier treatment with APC in sepsis has been associated with a better
      therapeutic response as compared to later treatment. In a mouse model it was
      recently confirmed that recombinant murine (rm-)APC decreases coagulation
      activation and improves survival in pneumococcal pneumonia; however, APC did not
      impact on the inflammatory response. The aim of this study was to determine the
      effect of APC treatment instigated early in infection on activation of
      coagulation and inflammation after induction of pneumococcal pneumonia. Mice were
      infected intranasally with viable  S. pneumoniae . Mice were treated with rm-APC
      (125 MUg) or vehicle intraperitoneally 12 hours after infection and were
      sacrificed after 20 hours, after which blood and organs were harvested for
      determination of bacterial outgrowth, coagulation activation and inflammatory
      markers. In this early treatment model, rm-APC treatment inhibited pulmonary and
      systemic activation of coagulation as reflected by lower levels of thrombin
      antithrombin complexes and D-dimer. Moreover, rm-APC reduced the levels of a
      large number of cytokines and chemokines in the lung. When administered early in
      pneumococcal pneumonia, rm-APC inhibits systemic and pulmonary activation of
      coagulation and moreover exerts various anti-inflammatory effects in the lung.

PMID- 21901241
TI  - Differential role of monocyte subsets in atherosclerosis.
AB  - Endothelial dysfunction and inflammation of the arterial wall continuously drive
      the development of atherosclerosis. Details regarding the sequential involvement
      of different monocyte subsets in the pathology of this disease have recently
      emerged. This review concentrates on major monocyte subpopulations in mouse and
      men and specifically addresses their phenotype, function and recruitment during
      primary atherosclerosis as well as their contribution to angiogenesis and tissue
      regeneration secondary to plaque rupture.

PMID- 21901242
TI  - Platelet activation in the pathogenesis of obesity and vascular disease.

PMID- 21901243
TI  - Risk of cervical cancer among female autoworkers exposed to metalworking fluids.
AB  - OBJECTIVES: Cervical cancer is caused by human papilloma virus (HPV). However,
      only a small proportion of women infected with HPV, progress to cervical cancer.
      Other co-factors must therefore be necessary to cause cervical cancer. We
      examined cervical cancer in relation to occupational exposure to metalworking
      fluids (MWF), which are complex mixtures containing several known carcinogens.
      METHODS: A cohort of 4374 female autoworkers was followed from 1985-2004 for
      cancer diagnosis. Based on standardized incidence rates (SIR), we focused on
      cervical cancer in an internal analysis. Pooled logistic regression was used to
      model the relationship between exposure to three different types of MWF, selected
      constituents, and incidence of cervical cancer. RESULTS: Based on 40 cases, SIR
      were statistically significantly elevated for both race specific subgroups: 3.30
      and 2.43, respectively for Caucasian and black women. The standard mortality
      ratio (SMR) was also statistically significantly elevated for Caucasian women
      (3.44) based on seven observed deaths. There was no association with oil-based
      straight fluid. Relative risks for soluble and synthetic MWF and nitrosamines
      were modestly elevated but not statistically significant. CONCLUSIONS: Water
      based MWF may play a role in the etiology of cervical cancer. Further studies in
      larger cohorts of women are needed to clearly establish this relationship.

PMID- 21901244
TI  - Abatacept is a promising treatment for patients with disseminated morphea
      profunda: presentation of two cases.
AB  - Morphea profunda is a rare disease that mainly affects young women and often has
      a progressive course with physical and psychological sequelae. The skin becomes
      sclerotic after an initial inflammatory reaction and joint contractures can
      develop. The aetiology is unknown. Until now, no successful therapy has been
      proven for this morphea variant. On the basis of new insights into the key role
      of effector T cells in scleroderma, in particular Th-17, T-cell directed
      therapies are expected to have promising effects. We report here the first two
      cases of morphea profunda treated with abatacept. Abatacept had a clinical effect
      on the active disease, in addition to softening old sclerotic lesions.

PMID- 21901245
TI  - Mitigation of 2,4-dinitrofluorobenzene-induced atopic dermatitis-related symptoms
      by Terminalia chebula Retzius.
AB  - To evaluate whether an aqueous seed extract of Terminalia chebula Retzius
      inhibited development of atopy in vivo, we used a 2,4-dinitrofluorobenzene (DNFB)
      induced animal model of atopic symptoms to investigate the effects of the
      extract. We measured CD4+ cell numbers by hematoxylin and eosin (H&E) staining,
      and determined the expression levels of matrix metalloproteinase (MMP)-9,
      interleukin (IL)-31, and T-bet genes, in this animal model. The data showed that
      a Terminalia chebula extract (100 ug/ml) exhibited strong anti-atopic activity,
      mediating a 52% reduction in the immune response, as measured by thickness of ear
      swelling, and resulting in decreased eosinophil levels in adjacent skin tissue.
      Collectively, the results indicate that a Terminalia chebula seed extract has
      potential for alleviation of atopy-like symptoms induced by DNFB in the mouse.

PMID- 21901246
TI  - Identification of a potent epigenetic biomarker for resistance to camptothecin
      and poor outcome to irinotecan-based chemotherapy in colon cancer.
AB  - Drug resistance remains a major obstacle to successful cancer treatment. Genome
      wide comprehensive analysis identified a novel gene, glucocorticoid-induced
      protein-coding gene (DEXI), which was frequently methylated in colorectal (CRC;
      36 of 73 patients; 49%) and gastric (28 of 89 patients; 31%) cancer patients.
      Here, we show that DEXI methylation is implicated in mechanisms facilitating
      resistance to camptothecin (CPT) via inhibition of apoptosis. Silencing of DEXI
      by siRNA significantly reduced CPT-induced apoptosis in a fibroblast cell line
      (1/6-fold; p<0.01) originally expressing endogenous DEXI. Restored expression of
      DEXI by 5-aza-2'-deoxycytidine (DAC) significantly enhanced susceptibility to CPT
      (3-fold; p<0.01) in a colon cancer cell line originally suppressing endogenous
      DEXI due to almost complete methylation. Exogenous induction of DEXI confirmed
      that DEXI per se contributed to enhanced susceptibility to CPT. 5-Fluorouracil (5
      FU) did not exhibit these synergistic effects by DEXI restoration. Further, to
      estimate the clinical usefulness of DEXI methylation status as biomarker for drug
      resistance to irinotecan (CPT-11), 16 CRC patients who underwent FOLFIRI (5-FU +
      CPT-11) therapy because they were refractory to FOLFOX (5-FU + oxaliplatin) were
      analyzed. Significantly poor response and outcome were observed in 8 CRC patients
      harboring DEXI methylation. In 8 CRC patients harboring DEXI methylation disease
      control rate, progression-free survival and overall survival were 25.0%, 2 and
      11.8 months, respectively, whereas in 8 CRC patients without DEXI methylation
      they were 62.5%, 5.3 and 15 months, respectively (p<0.01). These significant
      differences were not observed in patients undergoing treatment with FOLFOX. In
      conclusion, silencing of DEXI leads to resistance, but restored expression
      enhances susceptibility to CPT in vitro and DEXI methylation results in poor
      response and outcome to CPT-11-based chemotherapy, suggesting that DEXI is a
      potent therapeutic target and an epigenetic biomarker for the selection of
      patients more likely to benefit from CPT-11-based chemotherapy.

PMID- 21901247
TI  - Studies of genomic imbalances and the MYB-NFIB gene fusion in polymorphous low
      grade adenocarcinoma of the head and neck.
AB  - Polymorphous low-grade adenocarcinoma (PLGA) is a malignancy predominantly
      originating from the minor salivary glands. The molecular events underlying the
      pathogenesis of PLGA is poorly understood and no recurrent genetic aberrations
      have so far been identified. We used genome-wide, high-resolution aCGH analysis
      to explore genomic imbalances in 9 cases of PLGA. Because of the well-known
      morphologic similarities between PLGA and adenoid cystic carcinoma (ACC) we also
      analyzed all tumors for expression of the recently identified ACC-associated MYB
      NFIB gene fusion. aCGH analysis revealed that the PLGA genome contains
      comparatively few copy number alterations (CNAs). Gains/losses of whole
      chromosomes or chromosome arms were more than twice as common as partial CNAs.
      Two cases showed gain of chromosome 8 and one case each gain of chromosome 9,
      loss of chromosome 22 and loss of the Y chromosome. One case showed loss of the
      entire 6q arm and one case an interstitial deletion of a 33-Mb segment within
      6q22.1-q24.3. This region contains the MYB oncogene and the candidate tumor
      suppressor gene PLAGL1. RT-PCR analysis revealed that one of the 9 PLGAs
      expressed the ACC-associated MYB-NFIB gene fusion, illustrating the diagnostic
      difficulties associated with the diagnosis of these morphologically partly
      overlapping entities. Taken together, our findings indicate that the PLGA genome
      is genetically stable and contains comparatively few CNAs which is in line with
      the clinical observation that PLGA is a slow-growing, low-grade carcinoma with
      low metastatic potential.

PMID- 21901248
TI  - Fibulin-3 promoter methylation alters the invasive behavior of non-small cell
      lung cancer cell lines via MMP-7 and MMP-2 regulation.
AB  - Fibulin-3, an extracellular glycoprotein, has been suggested as having functions
      in tissue regeneration and organogenesis. However, its role in cancer remains
      unclear. We show here that fibulin-3 was silenced by hypermethylation of the
      promoter region in the relatively invasive A549 non-small cell lung cancer
      (NSCLC) cells compared with less invasive H460 NSCLC cells. Enforced expression
      of fibulin-3 in A549 cells down-regulated cellular MMP-7 and MMP-2, which was
      followed by inhibition of cell invasiveness. Conversely, suppression of fibulin-3
      expression with siRNA in H460 cells showed the opposite effect. These results
      indicate that fibulin-3 is a negative regulator of invasiveness in NSCLC and
      further studies are needed for its therapeutic applications in treatment of
      NSCLC.

PMID- 21901249
TI  - IKAROS isoform 6 enhances BCR-ABL1-mediated proliferation of human CD34+
      hematopoietic cells on stromal cells.
AB  - The BCR-ABL1 induces chronic myelogenous leukemia (CML) and Ph+ acute
      lymphoblastic leukemia (ALL). Recent studies revealed high ratios of loss of the
      IKZF1 gene which encodes IKAROS in BCR-ABL1+ ALL and lymphoblastic crisis (LBC)
      of CML. However, little is known about the cooperativity between the aberrant
      IKAROS and BCR-ABL1 in primary human hematopoietic cells. We investigated the
      effects of expression of BCR-ABL1 and/or IK6, a natural dominant negative isoform
      of IKAROS, on proliferation and differentiation of human CD34+ cord blood cells
      with or without human bone marrow-derived stromal cells which support early B
      cell differentiation. Cell proliferation was remarkably enhanced by co-expression
      of BCR-ABL1 and IK6, with reduced expression of glycophorin A and increased
      expression of CD41, especially on stromal cells, compared with expression of BCR
      ABL1 alone that resulted in expansion of erythroid progenitors. Interestingly,
      p190BCR-ABL1 showed higher dependency on stromal cells to stimulate cell growth
      with IK6, than p210BCR-ABL1. Furthermore, the cooperation was found to depend on
      direct cell adhesive interaction of hematopoietic progenitors with stromal cells.
      These findings suggest that IK6 and BCR-ABL1 synergistically contribute to
      leukemogenesis in human bone marrow stromal microenvironment, and may provide a
      clue to elucidate the mechanisms of leukemogenesis of Ph+ ALL and CML-LBC.

PMID- 21901250
TI  - Bufalin induces apoptosis through activation of both the intrinsic and extrinsic
      pathways in human bladder cancer cells.
AB  - Bufalin, a major digoxin-like immunoreactive component of the Chinese medicine
      Chansu, is prepared from toad venom. This compound has been shown to exert a
      potential for anticancer activity against various human cancer cell lines in
      vitro. However, the detailed molecular mechanisms of its induction of apoptosis
      are still unclear. In this study, we investigated the apoptosis-inducing effect
      of bufalin in T24 human bladder cancer cells. Our data revealed that bufalin
      treatment resulted in a concentration-response growth inhibition of T24 cells by
      inducing cell cycle arrest at the G2/M phase and apoptosis, as evidenced by
      formation of apoptotic bodies, chromatin condensation and accumulation of cells
      in the sub-G1 phase. Apoptosis induction of T24 cells by bufalin showed
      correlation with proteolytic activation of caspase-3, -8 and -9, and concomitant
      degradation of poly (ADP-ribose) polymerases, and collapse of the mitochondria
      membrane potential. In addition, bufalin treatment resulted in an increase of the
      Bax/Bcl-2 (or Bcl-xL) ratio and caused down-regulation of inhibitor of apoptosis
      protein (IAP) family members. The increase in apoptosis by bufalin treatment was
      also associated with up-regulation of death receptor-related factors. Our data
      indicate that the growth inhibitory effects of bufalin occur through blockade of
      the G2/M phase, and that these cancer cells do not enter cell cycle progression
      and die through apoptosis via both intrinsic and extrinsic pathways.

PMID- 21901251
TI  - Frequent loss of p19INK4D expression in hepatocellular carcinoma: relationship to
      tumor differentiation and patient survival.
AB  - p19INK4D belongs to the family of cyclin-dependent kinase inhibitors (CdkIs) that
      target the cyclin-dependent kinases and inhibit their catalytic activity. The
      role of p19INK4D in cell cycle progression in hepatocellular carcinoma (HCC) is
      poorly characterized. The aim of this study was to examine the expression of
      p19INK4D in various liver diseases including HCC and to assess its clinical
      significance in HCC. We examined the expression of p19INK4D by
      immunohistochemistry in 81 cases of various liver diseases, including 51 HCCs. We
      analyzed the relationship among p19INK4D expression in HCC in combination with
      histopathological stage, differentiation, several histopathological factors of
      possible prognostic value and patient survival. Immunohistochemical analysis
      revealed the frequent loss of p19INK4D expression consistent with the
      differentiation of HCC. The loss of p19INK4D expression was shown to be
      associated with a poor prognosis by analyzing clinicopathological features. In
      conclusion, we found that loss of p19INK4D protein was frequent in HCC,
      especially in poorly differentiated HCC, suggesting that p19INK4D may play a role
      in the differentiation of HCC. Furthermore, expression of p19INK4D may be an
      effective predictor of clinical behavior in HCC, and therefore, a new prognostic
      marker for HCC.

PMID- 21901252
TI  - Soluble mediators released from PI-IBS patients' colon induced alteration of mast
      cell: involvement of reactive oxygen species.
AB  - BACKGROUND: Growing evidence suggests that patients with post-infectious
      irritable bowel syndrome (PI-IBS) have increased mast cell activation, and that
      mucosal soluble mediators are involved in the pathophysiology of visceral
      hyperalgesia. In addition, previous findings show that reactive oxygen species
      (ROS) and protease-activated receptors (PARs) are mediators of persistent
      hyperalgesia. AIMS: This article aims to investigate: (1) the ability of soluble
      factors from colonic biopsies to active peritoneal mast cells (PMCs) in vitro;
      (2) whether the effects of PMCs degranulation induced by soluble mediators are
      related to PARs activation; and (3) the ability of phenyl N-tert-butylnitrone
      (PBN), a ROS scavenger, to modify these alterations. METHODS: Supernatant (SUP)
      from colonic biopsies was collected and applied to PMCs for 12 h. Activation of
      PMCs was evaluated. The expression of PAR(2) in PMCs was examined by RT-PCR and
      double-immunofluorescence staining. PBN (10 mM) treatment was administered, then
      previous alterations were observed again. RESULTS: Stimulation with SUP of PI-IBS
      led to an increase in activation of PMCs. PAR(2)mRNA expression was significantly
      increased in PMCs induced by SUP of PI-IBS compared to healthy subjects. After
      being treated by PBN, the SUP-induced enhancement of PMCs activities could be
      weakened, and PAR(2)mRNA expression was significantly decreased. A similar result
      of immunoreactivity for PAR(2) was observed in PMCs. CONCLUSIONS: The study shows
      that ROS scavenger reverses the SUP of PI-IBS-induced enhancement of PMCs
      activities, and that these effects may be related to activation of PAR(2). These
      findings might pave the way to new therapeutic targets in PI-IBS.

PMID- 21901253
TI  - Small bowel capsule endoscopy impacts diagnosis and management of pediatric
      inflammatory bowel disease: a prospective study.
AB  - PURPOSE: Accurately classifying inflammatory bowel disease (IBD) type in
      pediatric patients may impact medical decision-making, direct therapy, and
      improve outcomes. METHODS: This was a prospective cohort study evaluating
      classification of IBD and patient management with use of capsule endoscopy in
      pediatric patients with suspected or known IBD. Treating physicians completed a
      questionnaire before and after capsule endoscopy (CE) assessing clinical
      suspicion of Crohn's disease (CD) diagnosis, patient management decisions, and
      perceived impact of CE findings. RESULTS: Eighteen subjects [11F/7M, mean age
      13.8 (+/- 2.5) years], 4 previously diagnosed with CD, 4 with ulcerative or
      indeterminate colitis (UC/IC), and 10 "suspected" to have IBD were included.
      Following CE, 2 of 4 (50%) UC/IC patients were reclassified as having small bowel
      CD. In the 4 subjects with known CD, 2 (50%) had CE evidence of more proximal
      small bowel mucosal disease than previously recognized. In the 10 subjects with
      "suspected" IBD, 8 (80%) had SB ulcerations leading to a definitive diagnosis of
      CD. Treating physicians reported CE helped diagnosing CD in 15 of 18 (83.3%)
      subjects and impacted medical decision-making in 13 of 18 (72.2%), leading to a
      change in medical management in 14 of 18 (77.8%). CONCLUSIONS: In "suspected"
      pediatric IBD, CE often leads to a definitive diagnosis of CD. CE can lead to
      reclassification of IBD from UC/IC to CD and previously diagnosed CD patients may
      have a more significant burden of small bowel disease. These data may help
      integrate CE in evaluating IBD patients, lead to more targeted medical management
      changes and improve outcomes.

PMID- 21901254
TI  - Knockdown of RON inhibits AP-1 activity and induces apoptosis and cell cycle
      arrest through the modulation of Akt/FoxO signaling in human colorectal cancer
      cells.
AB  - BACKGROUND/AIMS: Altered Recepteur d'Origine nantais (RON) expression transduces
      signals inducting invasive growth phenotype that includes cell proliferation,
      migration, matrix invasion, and protection of apoptosis in human cancer cells.
      The aims of the current study were to evaluate whether RON affects tumor cell
      behavior and cellular signaling pathways including activator protein-1 (AP-1) and
      Akt/forkhead box O (FoxO) in human colorectal cancer cells. METHODS: To study the
      biological role of RON on tumor cell behavior and cellular signaling pathways in
      human colorectal cancer, we used small interfering RNA (siRNA) to knockdown RON
      gene expression in human colorectal cancer cell line, DKO-1. RESULTS: Knockdown
      of RON diminished migration, invasion, and proliferation of human colorectal
      cancer cells. Knockdown of RON decreased AP-1 transcriptional activity and
      expression of AP-1 target genes. Knockdown of RON activated cleaved caspase-3, 
      7, -9, and PARP, and down-regulated the expression of Mcl-1, survivin and XIAP,
      leading to induction of apoptosis. Knockdown of RON induced cell cycle arrest in
      the G2/M phase of cancer cells by an increase of p27 and a decrease of cyclin D3.
      Knockdown of RON inhibited the phosphorylation of Akt/FoxO signaling proteins
      such as Ser473 and Thr308 of Akt and FoxO1/3a. CONCLUSIONS: These results
      indicate that knockdown of RON inhibits AP-1 activity and induces apoptosis and
      cell cycle arrest through the modulation of Akt/FoxO signaling in human
      colorectal cancer cells.

PMID- 21901255
TI  - Driving simulation can improve insight into impaired driving skills in cirrhosis.
AB  - BACKGROUND: Minimal hepatic encephalopathy (MHE) is associated with poor driving
      skills and insight. Increasing insight may improve receptiveness for therapy or
      driving restrictions. AIM: To evaluate the change in the self-assessment of
      driving skills (SADS) using a driving simulator. METHODS: Cirrhotic patients and
      age/education-matched controls underwent MHE testing with inhibitory control
      (ICT) and the psychometric hepatic encephalopathy score (PHES). SADS, a Likert
      scale from 0 to 10, was administered just before and after a standardized driving
      simulation comprising testing and navigation tasks. The percentage SADS change
      from baseline was compared within/between groups. RESULTS: A total of 84 patients
      (60% men, age 55 years) and 12 controls were included. Controls were
      significantly better than cirrhotics on cognitive/simulator testing. The baseline
      SADS was similar between the groups. The baseline patient SADS was only
      correlated with ICT lures (r = -0.4, P = 0.001). Post-simulation, 60% of patients
      improved their insight, i.e., reduced SADS (from 8 to 6.5, P = 0.0001) compared
      to 25% of controls (P = 0.02). The mean percentage SADS reduction was also higher
      in cirrhotics (18% vs. 8%, P = 0.03). MHE on ICT patients had a significantly
      higher SADS improvement (P = 0.004) compared to the other patients; no difference
      was seen in those with/without MHE due to the PHES. The percentage SADS reduction
      in patients was correlated with getting lost (r = 0.468, P < 0.0001), crashes (P
      = 0.002), and centerline/road-edge excursions (P = 0.01). There was a
      significantly higher percentage SADS reduction in cirrhotics who got lost (25%)
      compared to those who did not get lost (12%) and controls (8%, P = 0.014).
      CONCLUSIONS: Insight into driving skills in cirrhosis improves after driving
      simulation and is highest in those with navigation errors and MHE on ICT. Driving
      simulator-associated insight improvement may be the first step towards the
      cognitive rehabilitation of driving skills in cirrhosis.

PMID- 21901256
TI  - Bifidobacterium longum with fructo-oligosaccharides in patients with non
      alcoholic steatohepatitis.
AB  - BACKGROUND: Increased exposure to intestinal bacterial products may contribute to
      the pathogenesis of non alcoholic steatohepatitis (NASH). Bifidobacteria are
      predominant bacterial species in the human gut microbiota and have been
      considered to exert a beneficial effect on human health by maintaining the
      equilibrium of the resident microbiota. AIMS: To evaluate the effects of
      Bifidobacterium longum with fructo-oligosaccharides (Fos) in the treatment of
      NASH. METHODS: A total of 66 patients were randomly and equally divided into two
      groups receiving Bifidobacterium longum with Fos and lifestyle modification
      (i.e., diet and exercise) versus lifestyle modification alone. The following
      variables were assessed at -4 (beginning of the dietary lead-in period), 0
      (randomization), 6, 12, 18, and 24 weeks: aspartate transaminase (AST), alanine
      transaminase (ALT), bilirubin, albumin, total cholesterol, high-density
      lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol,
      triglycerides, fasting plasma glucose, insulin, C-peptide, C-reactive protein
      (CRP), tumor necrosis factor (TNF)-alpha, homeostasis model assessment of insulin
      resistance (HOMA-IR), and serum endotoxins. Liver biopsies were performed at
      entry and repeated after 24 weeks of treatment. RESULTS: At the end of study
      period, we observed that the Bifidobacterium longum with Fos and lifestyle
      modification group versus the lifestyle modification alone group showed
      significant differences in the AST -69.6 versus -45.9 IU/mL (P < 0.05), LDL
      cholesterol -0.84 versus -0.18 mmol/L (P < 0.001), CRP -2.9 versus -0.7 mg/L (P <
      0.05), TNF-alpha -0.45 versus -0.12 ng/mL (P < 0.001), HOMA-IR -1.1 versus -0.6
      (P < 0.001), serum endotoxin -45.2 versus -30.6 pg/mL (P < 0.001), steatosis (P <
      0.05), and the NASH activity index (P < 0.05). CONCLUSIONS: Bifidobacterium
      longum with Fos and lifestyle modification, when compared to lifestyle
      modification alone, significantly reduces TNF-alpha, CRP, serum AST levels, HOMA
      IR, serum endotoxin, steatosis, and the NASH activity index.

PMID- 21901257
TI  - A multicenter survey of the management after gastric endoscopic submucosal
      dissection related to postoperative bleeding.
AB  - BACKGROUND AND AIMS: Bleeding is a major complication after gastric endoscopic
      submucosal dissection (ESD). An evidence-based strategy for postoperative care
      related to delayed bleeding is required. We conducted a multicenter survey to
      assess the current status of management after gastric ESD. METHODS: A total of
      1,814 gastric epithelial neoplasms in 2009 at ten tertiary referral centers were
      enrolled. The current status of the management after gastric ESD (use of an
      antisecretory drug, food intake, and second-look endoscopy) at participating
      hospitals was assessed. Furthermore, the rate of post-ESD bleeding and the
      differences in each parameter were retrospectively analyzed. RESULTS:
      Postoperative bleeding occurred in 100 cases (5.5%), which included 62 cases of
      bleeding within 24 h after ESD. In all of the hospitals, proton pump inhibitors
      (PPIs) were used. The median administration period was 56 days (range 14-60
      days). Food intake was resumed from postoperative day (POD) 1 in 4 hospitals and
      from POD 2 in 6 hospitals. Second-look endoscopy was performed for almost all
      cases, fewer cases, and rarely or none in 6, 2, and 2 hospitals, respectively.
      The day of second-look endoscopy varied among hospitals. There was no statistical
      relationship between the postoperative bleeding rate and the differences in these
      three parameters. CONCLUSIONS: Post-ESD management (duration of PPI use,
      resumption of food intake, and performance of second-look endoscopy) varied among
      the medical centers; thus, randomized controlled trials are required for an
      optimal strategy after gastric ESD.

PMID- 21901258
TI  - Dietary kaempferol suppresses inflammation of dextran sulfate sodium-induced
      colitis in mice.
AB  - BACKGROUND: In ulcerative colitis (UC), reduction of inflammation may represent a
      key mechanism in UC therapy, and anti-inflammatory agents would be good
      candidates for preventing UC. Kaempferol, a natural flavonoid, is believed to
      have anti-inflammatory activities and has been shown to be potentially immune
      modulatory. AIMS: The aim of this study was to determine whether kaempferol
      alleviates the inflammatory responses of dextran sulfate sodium (DSS)-induced
      colitis in mice. METHODS: Female C57BL/6J mice were divided into six groups: a
      negative control group, a DSS control group, and DSS + 0.1% or 0.3% kaempferol
      pre- or post-fed groups. At the end of the experimental period, clinical and
      biochemical markers were evaluated. RESULTS: Plasma levels of NO and PGE(2) were
      significantly decreased in both the 0.3% kaempferol pre- and post-fed groups. The
      plasma LTB(4) level was profoundly decreased in all animals fed kaempferol.
      Colonic mucosa MPO activity was also suppressed in both the 0.3% kaempferol pre-
      or post-fed groups. TFF3 mRNA, a marker for goblet cell function, was up
      regulated in kaempferol pre-fed animals. CONCLUSIONS: These results indicate that
      kaempferol is an effective anti-inflammatory agent that protects colonic mucosa
      from DSS-induced UC. Dietary kaempferol fed prior to colitis induction was more
      effective to suppress some of the colitis-associated markers.

PMID- 21901259
TI  - Erythrocyte deformability and oxidative stress in inflammatory bowel disease.
AB  - BACKGROUND: Oxidative stress and reduced microvascular flow are important factors
      in the pathogenesis of inflammatory bowel disease (IBD). The increased oxidative
      stress reduces the erythrocyte deformability. However, in IBD, there are no
      studies in the literature which evaluate erythrocyte deformability. AIMS: In our
      study, we investigated the effect of oxidative stress and erythrocyte
      deformability in IBD. METHODS: Forty-three patients with active IBD, 48 patients
      with inactive IBD and 45 healthy controls were included. The erytrocyte
      deformability, malonyldialdehyde levels, glutation peroxidase and sulfhydryl
      levels were measured in peripheral venous blood samples. RESULTS: Erytrocyte
      malonyldialdehyde levels in both active and inactive IBD were significantly
      increased compared with control groups. Plasma glutation peroxidase levels did
      not show statistically significant difference between all groups. The decreased
      plasma sulfhydryl levels in active IBD were statistically significant compared
      with both the inactive IBD and the control group, but plasma sulfhydryl levels in
      inactive IBD group did not show statistically significant differences when
      compared with the control group. Elongation index values in both active and
      inactive IBD increased significantly compared with the control group.
      Statistically significant correlations were not found between the elongation
      index and glutation peroxidase, malonyldialdehyde, sulfhydryl levels in all
      groups. CONCLUSIONS: Our study is the first to evaluate the erythrocyte
      deformability in IBD. In our study, increased erytrocyte malonyldialdehyde levels
      and decreased plasma sulfhydryl levels manifested the role of oxidative stress in
      the pathogenesis of the disease. It is thought that the increased erythrocyte
      malonyldialdehyde values cause the reduction in erythrocyte deformability.

PMID- 21901260
TI  - The severity of dextran sodium sulfate-induced colitis can differ between dextran
      sodium sulfate preparations of the same molecular weight range.
AB  - BACKGROUND: We hypothesized that the severity of dextran sodium sulfate (DSS)
      induced colitis could differ between DSS preparations of the same molecular
      weight, and that this difference may be affected by the sulfur content. To test
      this, we used three DSS preparations of similar molecular weights but with
      different sulfur contents. METHODS: Three DSS preparations with molecular weights
      of 40,000 to 50,000 were tested: MP Biomedicals (MP Bio), USB (USB), and The Lab
      Depot (The Lab). Epithelial cell lines were used to assess the levels of poly
      (ADP-ribose) polymerase (PARP) in the presence of 2.0% DSS in vitro. Eight-week
      old female C57/B6 mice were fed 2.0% DSS in water for 1 week, and then sacrificed
      to investigate the effects of the DSS preparations in vivo. RESULTS: In vitro
      experiments using CaCo-2 and CMT-93 cells revealed decreased PARP levels from all
      DSS preparations. Notably, the PARP level was significantly decreased in CaCo-2
      cells treated with DSS from USB as compared to The Lab Mice treated with The Lab
      DSS had significantly decreased body weight losses on day 7 as compared to mice
      receiving DSS from MP Bio and USB. This result was supported by their DAI score,
      colon weight/length ratio, and histological scores. CONCLUSION: The severity of
      colitis can differ between similar DSS preparations of the same molecular weight
      range. This difference in colitogenic properties may be affected by the total
      sulfur content of each DSS preparation.

PMID- 21901261
TI  - Prevention of induced colitis in mice by the ras antagonist farnesylthiosalicylic
      acid.
AB  - BACKGROUND: Ras proteins are crucial for cell differentiation and proliferation.
      Targeting Ras with farnesylthiosalicylic acid (FTS), a Ras antagonist, has been
      suggested as a therapeutic strategy in proliferative and inflammatory diseases.
      AIMS: To examine the role of Ras and the therapeutic potential of FTS in
      experimental colitis. METHODS: Colitis was induced in 26 mice by adding 2.5%
      dextran sodium sulfate to their drinking water for 7 days during which 12 study
      mice were treated with FTS and 14 control mice were given normal saline. Two
      additional controls included 10 naive mice treated with FTS and 7 naive non
      treated mice. The animals were followed clinically and sacrificed after 7 days.
      Their colons were isolated for histological assessment and for measurement of
      myeloperoxidase activity (MPO), tumor necrosis factor-alpha(TNF-alpha), and
      interleukin-1beta(Il-1beta) levels. Ras and activated Ras expression was
      determined by immunoblotting assays. T cell populations in the colon and spleen
      were analyzed by flow-cytometry. RESULTS: FTS induced a 2.1-fold reduction in
      activated Ras levels (P < 0.004). FTS-treated mice had lower disease activity
      scores (3.9 +/- 1.7 vs. 7.5 +/- 2.3, P < 0.001), and lower levels of MPO activity
      (1.65 +/- 0.6 vs. 2.6 +/- 0.8 units/g, P < 0.007), Il-1beta (2.4 +/- 3.6 vs. 24.3
      +/- 17.5 pg/mg, P < 0.01) and TNF-alpha (0.63 +/- 0.5 vs. 1.9 +/- 1 pg/mg, P <
      0.04). FTS increased regulatory T cell population in the spleen (1.9 +/- 0.4
      fold, P < 0.04), and decreased effector T cell populations in the colon and
      spleen by 24 +/- 3% (P < 0.03) and 27 +/- 1% (P < 0.02), respectively. FTS had no
      remarkable side effects. CONCLUSIONS: Ras is involved in the inflammatory
      processes of induced colitis in mice and its inhibition by FTS ameliorates the
      severity of the inflammation.

PMID- 21901262
TI  - Probe-based confocal laser microscopy identifies criteria predictive of active
      celiac sprue.
AB  - BACKGROUND: Celiac sprue is an underdiagnosed chronic intestinal inflammatory
      disease. Probe-based confocal laser microscopy (CLM) is a novel endoscopic
      technique for in vivo inspection of the intestinal mucosa that has not been
      evaluated in celiac sprue yet. AIMS: To develop CLM criteria most predictive of
      celiac pathology in a prospective pilot study. METHODS: Twenty-one patients (male
      n = 5, f = 16, mean age 52 years) with established or suspected celiac sprue,
      seven of whom had confirmed active disease (Marsh III) and 14 duodenal normal
      mucosa. CLM images from 91 duodenal sites were assessed. CLM recordings were
      obtained next to Argon beamer labeled areas. Biopsies were taken from the same
      spots for precise histological matching. After establishing histology-correlated
      criteria on one sample per patient, the remaining CLM recordings from the same
      patients were randomized and blindly evaluated. RESULTS: Villous atrophy and
      irregular appearing villi were most predictive of celiac pathology. Although the
      presence of crypts was diagnostic for celiac pathology, it was only recognized in
      26.7% of celiac pathology sites. Using these criteria in the blinded assessment,
      the overall endoscopist's prediction of celiac sprue was accurate in 89.8% of all
      biopsy sites in 85.7% of all patients. Preliminary interobserver agreement
      testing villous atrophy, irregular villi, and crypts was poor (kappa 0.05 to
      0.26). CONCLUSIONS: Probe-based CLM criteria developed in this pilot trial appear
      promising for the detection of active celiac sprue. Preliminary interobserver
      variability was high, indicating a learning curve effect. Our criteria need
      validation in an independent patient population.

PMID- 21901265
TI  - Pressure and coverage effects of sporting compression garments on cardiovascular
      function, thermoregulatory function, and exercise performance.
AB  - Sporting compression garments (CG) are used widely during exercise despite little
      evidence of benefits. The purpose of this study was to investigate coverage and
      pressure effects of full-body CG on cardiovascular and thermoregulatory function
      at rest and during prolonged exercise, and on exercise performance. Twelve
      recreationally trained male cyclists [mean (SD) age, 26 (7) years; VO(2 max), 53
      (8) mL kg(-1) min(-1)] completed three sessions (counterbalanced order), wearing
      either correctly-sized CG (CSG; 11-15 mmHg), over-sized CG (OSG; 8-13 mmHg), or
      gym shorts (CONT). Test sessions were conducted in temperate conditions [24 (1)
      degrees C, 60 (4)% relative humidity; ~2 m s(-1) air velocity during exercise],
      consisting of resting on a chair then on a cycle ergometer, before 60-min fixed
      load cycling at ~65% VO(2 max) and a 6-km time trial. Wearing CG (CSG or OSG) did
      not mitigate cardiovascular strain during mild orthostatic stress at rest (p =
      0.20-0.93 for garment effects). During exercise, cardiac output was ~5% higher in
      the CG conditions (p < 0.05), which appears to be accounted for via non
      significant higher end-exercise heart rate (~4-7%, p = 0.30; p = 0.06 for greater
      heart rate drift in CSG); other cardiovascular variables, including stroke
      volume, were similar among conditions (p = 0.23-0.91). Covered-skin temperature
      was higher in CG conditions (p < 0.001) but core (oesophageal) temperature was
      not (p = 0.79). Time-trial performance (mean power, time taken) was similar with
      or without CG (p = 0.24-0.44). In conclusion, any demonstrable physiological or
      psychophysical effects of full-body CG were mild and seemingly reflective more of
      surface coverage than pressure. No benefit was evident for exercise performance.

PMID- 21901266
TI  - Strength training elevates HSP27, HSP70 and alphaB-crystallin levels in musculi
      vastus lateralis and trapezius.
AB  - A single bout of high-force exercise has been shown to increase the muscle levels
      of heat shock proteins (HSPs). Here, changes in the levels of HSPs after 2 and 11
      weeks of strength training with either one or three sets per exercise were
      examined. Fifteen young men (27 +/- 6 years, 182 +/- 8 cm and 82 +/- 13 kg) were
      randomized to train either one set in lower-body exercises and three sets in
      upper-body exercises (1L-3UB), or three sets in lower-body exercises and one set
      in upper-body exercises (3L-1UB). Biopsies from vastus lateralis and trapezius
      were obtained before, during (2 weeks) and after 11 weeks of strength training (3
      bouts per week). The biopsies were analysed for HSP27 (cytosolic and cytoskeletal
      fractions) and HSP70 and alphaB-crystallin (cytosolic fraction). No evidence for
      an effect of training volume (1 vs. 3 sets) on the HSP response was found. For
      all subjects combined, HSP27 [186 +/- 69% (mean +/- SD)], HSP70 (146 +/- 51%) and
      alphaB-crystallin (184 +/- 82%) increased in the cytosolic fraction of vastus
      lateralis after 11 weeks of training. In the trapezius, the only observed
      increase was for HSP27 in the cytosolic fraction after 2 weeks of training (149
      +/- 59%). However, the trapezius contained somewhat higher levels of HSP70 and
      alphaB-crystallin than vastus lateralis at baseline. The HSP27 levels in the
      cytoskeletal compartment did not increase significantly in either muscle. In
      conclusion, strength training resulted-independent of training volume-in elevated
      levels of HSP27, HSP70 and alphaB-crystallin in the cytosolic compartment of the
      vastus lateralis. In the trapezius, only the cytosolic HSP27 levels were
      increased with training.

PMID- 21901267
TI  - Electroconvulsive therapy can benefit from controlled hyperventilation using a
      laryngeal mask.
AB  - Hypocapnia through hyperventilation is a well-known procedure in
      electroconvulsive therapy (ECT) to enhance seizure activity. However, it has
      mostly been applied in an uncontrolled manner. Originally intended for a better
      management of the supraglottic airway, laryngeal masks are more suited to monitor
      levels of CO(2) during hyperventilation than face masks and thereby provide for
      the possibility of controlled hyperventilation (CHV). The impact of CHV was
      retrospectively studied in 114 consecutive patients; 65 of them had received ECT
      with CHV and 49 had received ECT with uncontrolled hyperventilation (UHV)
      directly prior to the time period when the laryneal mask was introduced to the
      ECT treatment procedure. The CO(2) level in the CHV group was aimed at 30 mmHg or
      below. CHV considerably enhanced the seizure activity leading to changes in
      clinically determined parameters of the treatment course: the necessity for
      increasing the electric charge, for re-stimulations (trend) and for bilateral
      stimulations was lower in the CHV group as compared to the UHV group. The
      improvement in the Global Assessment of Functioning Scores was not different in
      both groups. CHV was associated with a higher amount of prolonged seizures, with
      a reduced number of delirious symptoms after treatments and an attenuating effect
      on heart rate. Concluding, CHV can help to maintain the applied electric charge
      low without worsening the clinical outcome. Therefore, it is a helpful technical
      improvement. However, it should be used carefully with regard to prolonged
      seizures.

PMID- 21901268
TI  - Sport psychiatry and psychotherapy. Mental strains and disorders in professional
      sports. Challenge and answer to societal changes.
AB  - Professional athletes are subject to massive somatic, social, and mental stress.
      Despite great public interest for athletic achievements, the emotional strains
      thereof are very poorly investigated and discussed. The main reason for this is
      the widespread assumption that only emotionally very strong athletes are able to
      compete at the highly professional level and therefore mental disorders do not
      exist in professional sports. But available research data about the prevalence of
      mental disorders in this area suggest that this hypothesis must be revised. With
      respect to depression and the overtraining syndrome, attempts have been made to
      demonstrate the difficulties with etiology, diagnostics, and treatment for sports
      psychiatry and psychotherapy. Scientifically, sport psychiatry and psychotherapy
      can be defined as a discipline, whose focus is the investigation, treatment, and
      prevention of the extreme and sports-specific emotional strains and disorders. In
      addition to sport psychology, which focuses mainly on performance enhancement,
      mental stress, and disorders can hereby be recognized, disorders be treated and
      the athletic performance sustained. With the foundation of the Task Force for
      Sports Psychiatry and Psychotherapy at the German Association for Psychiatry and
      Psychotherapy, scientific research, further education, prevention, and treatment
      for mental disorders in professional sports will be improved.

PMID- 21901269
TI  - A promoter variant of SHANK1 affects auditory working memory in schizophrenia
      patients and in subjects clinically at risk for psychosis.
AB  - Mutations in postsynaptic scaffolding genes contribute to autism, thus suggesting
      a role in pathological processes in neurodevelopment. Recently, two de novo
      mutations in SHANK3 were described in schizophrenia patients. In most cases,
      abnormal SHANK3 genotype was also accompanied by cognitive disruptions. The
      present study queries whether common SHANK variants may also contribute to
      neuropsychological dysfunctions in schizophrenia. We genotyped five common coding
      or promoter variants located in SHANK1, SHANK2 and SHANK3. A comprehensive test
      battery was used to assess neuropsychological functions in 199 schizophrenia
      patients and 206 healthy control subjects. In addition, an independent sample of
      77 subjects at risk for psychosis was analyzed for replication of significant
      findings. We found the T allele of the SHANK1 promoter variant rs3810280 to lead
      to significantly impaired auditory working memory as assessed with digit span
      (12.5 +/- 3.6 vs. 14.8 +/- 4.1, P < .001) in schizophrenia cases, applying strict
      Bonferroni correction for multiple testing. This finding was replicated for
      forward digit span in the at-risk sample (7.1 +/- 2.0 vs. 8.3 +/- 2.0, P = .044).
      Previously, altered memory functions and reduced dendritic spines and
      postsynaptic density of excitatory synapses were reported in SHANK1 knock-out
      mice. Moreover, the atypical neuroleptic clozapine was found to increase SHANK1
      density in rats. Our findings suggest a role of SHANK1 in working memory deficits
      in schizophrenia, which may arise from neurodevelopmental changes to prefrontal
      cortical areas.

PMID- 21901270
TI  - Progression of coronary artery calcification in black and white women: do the
      stresses and rewards of multiple roles matter?
AB  - BACKGROUND: Black women experience higher rates of cardiovascular disease (CVD)
      than white women, though evidence for racial differences in subclinical CVD is
      mixed. Few studies have examined multiple roles (number, perceived stress, and/or
      reward) in relation to subclinical CVD, or whether those effects differ by race.
      PURPOSE: The aim of this study was to investigate the effects of multiple roles
      on 2-year progression of coronary artery calcium. METHODS: Subjects were 104
      black and 232 white women (mean age 50.8 years). Stress and reward from four
      roles (spouse, parent, employee, caregiver) were assessed on five-point scales.
      Coronary artery calcium progression was defined as an increase of >=10 Agatston
      units. RESULTS: White women reported higher rewards from their multiple roles
      than black women, yet black women showed cardiovascular benefits from role
      rewards. Among black women only, higher role rewards were related significantly
      to lower progression of coronary artery calcium, adjusting for body mass index,
      blood pressure, and other known CVD risk factors. Blacks reported fewer roles but
      similar role stress as whites; role number and stress were unrelated to coronary
      artery calcium progression. CONCLUSION: Rewarding roles may be a novel protective
      psychosocial factor for progression of coronary calcium among black women.

PMID- 21901271
TI  - Elevated gamma-glutamyltransferase in implantable cardioverter defibrillator
      patients.
AB  - BACKGROUND: Elevated gamma-glutamyltransferase (GGT) is a new risk factor for
      cardiovascular diseases, but its impact on ventricular tachyarrhythmia occurrence
      and survival in patients with an implantable cardioverter defibrillator (ICD) is
      unknown. METHODS AND RESULTS: Considering that GGT levels are gender-dependent,
      female ICD recipients were excluded from our database because of the low
      incidence of events. In a retrospective analysis, appropriate ICD therapy (both
      shocks and antitachycardia pacing due to ventricular tachyarrhythmias) occurred
      in 31.9% of 320 male patients who had received an ICD for primary prevention
      (median follow-up of 2.3 years), and in 55.1% of 423 male patients who had
      received an ICD for secondary prevention (median follow-up of 3.9 years).
      Compared to normal low GGT plasma levels (below 28 U/L), total mortality but not
      risk for appropriate ICD therapy was elevated for higher GGT categories (p for
      trend = 0.004 in primary prevention and p for trend = 0.002 in secondary
      prevention, respectively). In Cox regression analysis, elevated GGT (>56 U/L)
      remained an independent predictor of death both in primary (p = 0.011) and in
      secondary prevention (p = 0.006). Patients with elevated GGT and renal
      insufficiency defined by an estimated glomerular filtration rate <60 ml/min/1.73
      m(2) suffered from excess total mortality jeopardizing the benefit of ICD
      therapy. CONCLUSION: Elevation of GGT is an important adverse prognostic
      parameter in ICD patients. A possible role of GGT for improved patient selection
      for ICD therapy deserves further investigation.

PMID- 21901272
TI  - [Clinical practise guideline of the special interest group in allergy of the OGDV
      - Drug provocation testing in the diagnosis of cutaneous drug reactions].
AB  - Nowadays, clinical and evidence based guidelines are considered one of the major
      efforts to improve patient care in medical practices as well as hospital
      settings. In the literature, clinical guidelines have been defined as
      "systematically developed statements to assist practitioner and patient decisions
      about appropriate healthcare for specific clinical circumstances", which promote
      both clinically effective standards and cost-effective care. Despite
      controversial discussion about the clinical impact of guidelines, they may
      provide workable recommendations that may thus be important for improving the
      individual patient's care. Adverse drug reactions (drug allergies, drug
      hypersensitivities) often represent a major hazard for the affected patient, and
      a definite diagnosis is important for further drug therapies in most cases. In
      this context, any diagnostic procedure must be preceded by an individual risk
      benefit assessment. Drug provocation testing is regarded as the gold standard,
      but this kind of testing should be performed in accordance with established
      criteria and, in the vast majority of cases, in a hospital setting. In this paper
      we present a clinical guideline for drug provocation testing in Austria.

PMID- 21901273
TI  - Serum amyloid a protein in clinical cancer diagnosis.
AB  - The serum amyloid A (SAA) protein is an acute phase protein that is synthesized
      under the regulation of inflammatory cytokines during both acute and chronic
      inflammation. It is suggested that the SAA increases correlate with many types of
      carcinogenesis and neoplastic diseases. Th changes in SAA in serum could
      therefore indicate the progress and malignancy of the disease, as well as the
      host responses. The present paper reviewed the rationale of using SAA as
      potential cancer biomarker in clinical diagnosis, including the contribution and
      involvement of SAA in cancer growth and development. Then we discussed the
      current applications of SAA in diagnosis and tracing of different types of
      cancers. Finally the proteomics techniques, especially the SELDI-TOF MS to
      identify SAA in serum from patients were appreciated as an important manner in
      clinical diagnosis.

PMID- 21901274
TI  - Biochemical and morphological differences between CA125 isolated from healthy
      women and patients with epithelial ovarian cancer from Tunisian population.
AB  - Analysis of the structure of CA125 is essential for determining the physiological
      role of this significant tumor antigen. The objectives of this study were: (1) to
      identify the characteristics of the CA125 isolated from healthy and patient women
      with epithelial ovarian cancer; and (2) to determine the ferning structure of
      this antigen. The cancer-derived CA125 antigen (cCA125) purified by gel
      filtration and affinity chromatography (Concanavalin A) was run on SDS-PAGE and
      examined using light microscopy and compared with healthy-derived CA125 antigen
      (hCA125). Both purified antigen cCA125 and hCA125 showed a high molecular mass (>
      2,000 kDa) with high mannose glycans. The ferning patterns related to cCA125 and
      hCA125 revealed distinct differences in the patterns of arborescence. The ferning
      morphology of cCA125 antigen was denser than that of hCA125 antigen making an
      obvious difference between cCA125 and hCA125, with respect to length, branching
      and distribution of crystals. The current study provides the first evidence for a
      potential functional link between CA125 and its structure which, in the light of
      a comparison between cCA125 and hCA125, might proof to be of significant
      biomedical importance in the future.

PMID- 21901275
TI  - Allelic loss of 10q23.3, the PTEN gene locus in cervical carcinoma from Northern
      Indian population.
AB  - Cervical cancer is one of the most common malignant diseases affecting women
      worldwide. Studies on loss of heterozygosity have been made for PTEN gene
      specific microsatellite markers in malignancies like breast, ovary and lungs and
      the results have shown a significant association. However the role of this gene
      is not clearly understood in cervical cancer from Indian population. A total of
      135 cervical carcinoma tissues samples were analyzed for loss of heterozygosity.
      DNA was isolated from the samples and their matched control specimens. Polymerase
      chain reaction was performed using primer specific for two intragenic markers
      (D10S198 & D10S192) and one marker (D10S541) in flanking region and further
      electrophoresed on 8% denaturing polyacrylamide gel. Overall, 31 out of 133(23%)
      informative cases showed loss of heterozygosity in at least one locus in the
      region examined. The percentage of loss of heterozygosity for these markers
      ranged from 8% (D10S192) to 13% (D10S198). Loss of heterozygosity was more
      frequently detected in intragenic region (D10S198 & D10S192) than in flanking
      region, D10S541 (21% versus 9%). These data argue that PTEN is a tumor suppressor
      gene whose inactivation may play an important role in the carcinoma of uterine
      cervix.

PMID- 21901276
TI  - Role of organ transplantation in the treatment of malignancies: hepatocellular
      carcinoma as the most common tumour treated with transplantation.
AB  - There are only few malignant tumours where organ transplantation is the treatment
      of choice. Transplantation can be considered individually in certain lung
      carcinomas, unresectable heart tumours, cholangiocellular carcinoma and Klatskin
      tumour. It is acceptable in unresectable chemosensitive hepatoblastoma,
      epitheloid haemangioendothelioma, liver metastasis of neuroendocrine tumours and
      as the most common indication, the early hepatocellular carcinoma (HCC) in
      cirrhotic liver. Results of liver transplantation (LT) for HCC according to Milan
      criteria as a "gold standard" are excellent. Time of LT has a great influence on
      the results. While patients are on waiting list, locoregional therapies may help
      prevent tumour progress. Living donor LT is an acceptable treatment of HCC. The
      greatest experience with this procedure is in Asia. Despite the favourable
      results, LT as the treatment of HCC is debated and raises several questions:
      regarding indication and expectable outcome. Milan criteria seem to answer this
      questions although they are too strict. The number and size of HCC foci per se is
      not sufficient predictor of eligibility to transplantation and for prognosis.
      Majority of the prognostic factors can be evaluated only after transplantation
      with pathological examination of HCC. Aim of the present research is to find
      prognostic factors that are characteristic of biological behaviour of HCC, which
      can be detected before LT in order to select patients who have the greatest
      benefit from LT. Re-definition of eligibility criteria is an actual question; an
      international consensus based on additional prospective studies is required for
      the "new" recommendation.

PMID- 21901277
TI  - Heterologous expression of the chrysanthemum R2R3-MYB transcription factor CmMYB2
      enhances drought and salinity tolerance, increases hypersensitivity to ABA and
      delays flowering in Arabidopsis thaliana.
AB  - Knowledge on genes related to plant responses to adverse growth conditions and
      development is essential for germplasm improvement. In this study, a
      chrysanthemum R2R3-MYB transcription factor gene, designated CmMYB2 (GenBank
      accession No. JF795918), was cloned and functionally characterized. Expression of
      CmMYB2 in chrysanthemum leaves was up-regulated in response to drought, salinity
      and cold stress, as well as by treatment with exogenous abscisic acid (ABA). When
      the gene was constitutively expressed in Arabidopsis thaliana, it increased plant
      sensitivity to ABA and reduced stomatal aperture. Plant survival under drought
      was improved than in the wild type, as was the plants' salinity tolerance. The
      level of expression of a number of genes associated with the stress response,
      including RD22, RD29A, RAB18, COR47, ABA1 and ABA2, was raised in the CmMYB2
      transgenic Arabidopsis plants. CmMYB2 transgenic Arabidopsis plants were also
      delayed in flowering. The expression of CONSTANS (CO), FLOWERING LOCUS T (FT),
      SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1), LEAFY (LFY) and APETALA1 (AP1)
      genes involved in flowering was down-regulated in the CmMYB2 transgenics.
      Together, these results suggest that CmMYB2 may be a promising gene for the
      drought and salt tolerance improvement and flowering-time modulation.

PMID- 21901278
TI  - Development of vaccine delivery vehicles based on lactic acid bacteria.
AB  - Live recombinant bacteria represent attractive antigen delivery systems able to
      induce both mucosal and systemic immune responses against heterologous antigens.
      The first live recombinant bacterial vectors developed were derived from
      attenuated pathogenic microorganisms. In addition to the difficulties often
      encountered in the construction of stable attenuated mutants of pathogenic
      organisms, attenuated pathogens may retain a residual virulence level that
      renders them unsuitable for the vaccination of partially immunocompetent
      individuals such as infants, the elderly or immunocompromised patients. As an
      alternative to this strategy, non-pathogenic food-grade lactic acid bacteria
      (LAB) maybe used as live antigen carriers. This article reviews LAB vaccines
      constructed using antigens other than tetanus toxin fragment C, against
      bacterial, viral, and parasitic infective agents, for which protection studies
      have been performed. The antigens utilized for the development of LAB vaccines
      are briefly described, along with the efficiency of these systems in protection
      studies. Moreover, the key factors affecting the performance of these systems are
      highlighted.

PMID- 21901279
TI  - European Working Time Directive and the use of simulators and models in Irish
      orthopaedics.
AB  - OBJECTIVE: To report on the perceptions of a group of orthopaedic trainees and
      trainers on perceived effects of the proposed introduction of European Working
      Time Directive (EWTD) restrictions into Ireland and on the use of simulators in
      training orthopaedic skills. METHODS: A structured questionnaire was developed to
      evaluate the opinions of a group of orthopaedic surgeons and trainees at the
      annual national orthopaedic conference. RESULTS: There were 44 participants [12
      consultants, 32 trainees (15 specialist registrars, 8 registrars, 9 senior house
      officers)]. Seventy-five percent of participants felt that both the quality of
      patient care and training would be negatively affected. A higher proportion of
      consultants than trainees felt that quality of life would be affected. A high
      proportion of participants (81.8%) had used a simulator or model to learn a
      surgical skill and 100% would consider using them again. CONCLUSIONS: While we
      wait for the full introduction of the EWTD hours the perception is that both
      quality of patient care and training will be affected. Models and simulators are
      well perceived as a method of training.

PMID- 21901280
TI  - Chromatin occupancy of transcription factor 7-like 2 (TCF7L2) and its role in
      hepatic glucose metabolism.
AB  - AIMS/HYPOTHESIS: The mechanisms by which transcription factor 7-like 2 (TCF7L2)
      regulates the pathways that are important in the pathogenesis of type 2 diabetes
      are unknown. We therefore examined the role of TCF7L2 in hepatic glucose
      production (HGP) in vitro and characterised the whole-genome chromatin occupancy
      of TCF7L2 in hepatocytes. METHODS: We investigated the effect of TCF7L2 silencing
      and overexpression on HGP from gluconeogenic precursors and used chromatin
      immunoprecipitation (ChIP) combined with massively parallel DNA sequencing (ChIP
      Seq) to investigate the DNA binding patterns of TCF7L2 across the whole genome.
      RESULTS: Silencing of TCF7L2 induced a marked increase in basal HGP, which was
      accompanied by significant increases in the expression of the gluconeogenic genes
      Fbp1, Pck1 and G6pc. Overexpression of Tcf7l2 reversed this phenotype and
      significantly reduced HGP. TCF7L2 silencing did not affect the half-maximal
      inhibitory concentration of insulin or metformin, but HGP remained elevated in
      TCF7L2-silenced cells due to the increased baseline HGP. Using ChIP-Seq, we
      detected 2,119 binding events across the genome. Pathway analysis demonstrated
      that diabetes genes were significantly over-represented in the dataset. Our
      results indicate that TCF7L2 binds directly to multiple genes that are important
      in regulation of glucose metabolism in the liver, including Pck1, Fbp1, Irs1,
      Irs2, Akt2, Adipor1, Pdk4 and Cpt1a. CONCLUSIONS/INTERPRETATION: TCF7L2 is an
      important regulator of HGP in vitro and binds directly to genes that are
      important in pathways of glucose metabolism in the liver. These data highlight
      the possibility that TCF7L2 may affect fasting and postprandial hyperglycaemia in
      carriers of at-risk TCF7L2 genetic polymorphisms.

PMID- 21901281
TI  - Nicotinamide mononucleotide protects against pro-inflammatory cytokine-mediated
      impairment of mouse islet function.
AB  - AIMS/HYPOTHESIS: Nicotinamide phosphoribosyltransferase (NAMPT), the rate
      limiting enzyme for NAD(+) biosynthesis, exists as intracellular NAMPT (iNAMPT)
      and extracellular NAMPT (eNAMPT). eNAMPT, secreted from adipose tissue, promotes
      insulin secretion. Administration of nicotinamide mononucleotide (NMN), a product
      of the eNAMPT reaction, corrects impaired islet function in Nampt ( +/- ) mice.
      One of its potential targets is the NAD(+)-dependent deacetylase sirtuin 1. We
      hypothesised that altered NAMPT activity might contribute to the suppression of
      islet function associated with inflammation, and aimed to determine whether NMN
      could improve cytokine-mediated islet dysfunction. METHODS: Acute effects of NMN
      on cytokine-mediated islet dysfunction were examined in islets incubated with
      TNFalpha and IL1beta, and in mice fed a fructose-rich diet (FRD) for 16 weeks.
      Changes in iNAMPT, eNAMPT and inflammation levels were determined in FRD-fed
      mice. RESULTS: FRD-fed mice displayed markedly lower levels of circulating
      eNAMPT, with impaired insulin secretion and raised islet expression of Il1b. NMN
      administration lowered Il1b expression and restored suppressed insulin secretion
      in FRD-fed mice. NMN also restored insulin secretion in islets cultured with pro
      inflammatory cytokines. The changes in islet function corresponded with changes
      in key markers of islet function and differentiation. The anti-inflammatory
      effects of NMN were partially blocked by inhibition of sirtuin 1.
      CONCLUSIONS/INTERPRETATION: Chronic fructose feeding causes severe islet
      dysfunction in mice. Onset of beta cell failure in FRD-fed mice may occur via
      lowered secretion of eNAMPT, leading to increased islet inflammation and impaired
      beta cell function. Administration of exogenous NMN to FRD-fed mice corrects
      inflammation-induced islet dysfunction. Modulation of this pathway may be an
      attractive target for amelioration of islet dysfunction associated with
      inflammation.

PMID- 21901282
TI  - Vitamin D deficiency as a risk factor for cystic fibrosis-related diabetes in the
      Scandinavian Cystic Fibrosis Nutritional Study.
AB  - AIMS/HYPOTHESIS: Many cystic fibrosis patients are vitamin D-insufficient. Cystic
      fibrosis-related diabetes is a major complication of cystic fibrosis. The
      literature suggests that vitamin D might possess certain glucose-lowering
      properties. We aimed to assess the relationship between vitamin D and cystic
      fibrosis-related glucose intolerance. METHODS: We enrolled 898 cystic fibrosis
      patients from Sweden, Norway and Denmark. Vitamin D intake was assessed using a
      seven-day food record. Serum 25-hydroxyvitamin D (s25OHD) and HbA(1c) were
      measured, and an OGTT was carried out. Multiple linear and logistic regressions
      were used for HbA(1c) and cystic fibrosis-related diabetes/OGTT result as outcome
      variables, respectively. Each model was controlled for country, and for known
      cystic fibrosis-related diabetes risk factors: age, sex, genotype, liver
      dysfunction, long-term corticosteroid treatment, and lung and pancreatic
      function. RESULTS: Degree of vitamin D insufficiency (OR 1.36; p = 0.032) and
      s25OHD < 30 nmol/l (OR 1.79; p = 0.042) were significant risk factors for cystic
      fibrosis-related diabetes. Accordingly, HbA(1c) value was positively associated
      with s25OHD < 30 nmol/l and < 50 nmol/l, as well as with degree of vitamin D
      insufficiency (adjusted R (2) = 20.5% and p < 0.05 in all). In subgroup analyses,
      s25OHD < 30 nmol/l determined the HbA(1c) value in paediatric patients (adjusted
      R (2) = 20.2%; p = 0.017), but not in adults. CONCLUSIONS/INTERPRETATION: Vitamin
      D status is associated with HbA(1c) and diabetes in cystic fibrosis, particularly
      in children. The study justifies prospective studies on the proposed role of
      vitamin D deficiency in the pathophysiology of diabetes mellitus.

PMID- 21901284
TI  - Skin sensory function in post-bariatric patients-implications for selection of
      post-bariatric abdominal body-contouring techniques.

PMID- 21901283
TI  - Investigation of antidepressant medication usage after bariatric surgery.
AB  - BACKGROUND: Many patients seeking bariatric surgery have a history of mood
      disorders and are actively prescribed antidepressants. While extensive
      documentation exists on the impact of weight loss surgery on reductions in
      cardiac, diabetic, and hypertensive medications, little is known about the impact
      of bariatric surgery on the use of antidepressant medications. METHODS: A
      retrospective study of 439 patients who had undergone Roux-en-Y gastric bypass
      (RYGB) from January 2001 to November 2004 was examined for postoperative changes
      in the use of antidepressant medications. RESULTS: After RYGB, 23% of the
      patients had an increase in their antidepressant use, 40% continued to require
      the same antidepressant, 18% had a change in antidepressant medication, and only
      16% had a decrease or discontinued their antidepressant. CONCLUSION: Unlike most
      medications, antidepressant usage did not decrease in the majority of patients
      after RYGB. These results highlight the prevalence of antidepressant prescription
      use in patients before and after RYGB and support the need for the careful
      monitoring of depressive symptoms.

PMID- 21901285
TI  - Intragastric balloon in association with lifestyle and/or pharmacotherapy in the
      long-term management of obesity.
AB  - BACKGROUND: Intragastric balloon (BioEnterics Intragastric Balloon, BIB(r)) or
      pharmacotherapy are possible options for the treatment of obese patients when
      traditional approaches have failed. The aim of our study was to compare in obese
      patients the effect on weight loss and metabolic changes of lifestyle
      modifications associated with either BIB or pharmacotherapy or the two treatments
      in sequence as a maintenance strategy for weight loss. METHODS: Fifty obese
      patients were recruited and randomly assigned to lifestyle modifications combined
      with either BIB for 6 months (n = 30) or sibutramine (pharmacotherapy group) for
      1 year (n = 20). After BIB removal, patients were randomly assigned to either
      correct lifestyle (BIB/lifestyle) or lifestyle plus pharmacotherapy
      (BIB/pharmacotherapy). RESULTS: At 6 months, patients treated with BIB lost
      significantly (P < 0.05) more weight (percent of initial weight lost, %IWL = 14.5
      +/- 1.2; percent of excess BMI lost, %EBL = 37.7 +/- 3.2) than patients who
      received pharmacological treatment (%IWL = 9.1 +/- 1.5, %EBL = 25.3 +/- 4.1). At
      1 year, the weight lost was significantly (P < 0.05) greater in patients treated
      with either BIB/pharmacotherapy (%IWL = 15.8 +/- 2.3%, %EBL = 41.3 +/- 6.7%) or
      BIB/lifestyle (%IWL = 14.3 +/- 2.7, %EBL = 34.9 +/- 6.5%) in respect to
      pharmacotherapy group (%IWL = 8.0 +/- 1.4%, %EBL = 22.1 +/- 3.9%). Moreover,
      patients treated sequentially with BIB/lifestyle or BIB/pharmacotherapy showed a
      significant (P < 0.05) improvement in insulin sensitivity and triglycerides
      levels. CONCLUSIONS: BIB represents an efficacious long-term obesity treatment
      when supplemental strategies, as lifestyle modifications or pharmacotherapy, are
      established for weight maintenance after its removal.

PMID- 21901286
TI  - Prevalence of liver steatosis and fibrosis and the diagnostic accuracy of
      ultrasound in bariatric surgery patients.
AB  - BACKGROUND: Liver steatosis can progress to fibrosis, cirrhosis, and eventually
      to end-stage liver disease and hepatocellular carcinoma. We thus determined the
      prevalence of liver steatosis and fibrosis in patients undergoing bariatric
      surgery using liver biopsy. We also determined the suitability of ultrasound for
      diagnosis of liver steatosis with and without simultaneously considering patient
      characteristics. METHODS: We reviewed preoperative liver ultrasound and
      intraoperative liver biopsy results in 451 bariatric surgery patients along with
      their clinical characteristics between 2005 and 2009. RESULTS: Among 435 patients
      with conclusive biopsy results, estimated prevalence of liver steatosis was 71.5%
      (95% confidence interval 67%, 76%) and that of fibrosis was 27% (23%, 31%).
      Sensitivity of ultrasound for liver steatosis was 86% (82%, 90%); its specificity
      was 68% (59%, 76%). Positive predictive value of ultrasound for liver steatosis
      was 87% (82%, 91%), and its negative predictive value was 67% (58%, 75%). Overall
      diagnostic accuracy was 81% (77% 85%). Sensitivity was improved in patients with
      higher nonalcoholic fatty liver disease activity scores (NAS) [odds ratio (OR)
      1.4 (1.1, 1.9) for a one unit increase in NAS] and prolonged duration of obesity
      [OR 1.3 (1.1, 1.6) for a 5-year increase in duration] but was worsen by higher
      body mass index. CONCLUSIONS: About three quarters of bariatric surgery patients
      have liver steatosis, and about a quarter have fibrosis. One third of patients
      with liver steatosis develop fibrosis without significant clinical
      manifestations. Ultrasound was only moderately diagnostic for liver steatosis but
      was sufficient for clinical use in patients with a NAS score >=2 and when the
      duration of obesity was >30 years.

PMID- 21901287
TI  - Trabeculectomy or modified deep sclerectomy in juvenile uveitic glaucoma.
AB  - PURPOSE: The purpose of this study is to report the effectiveness of
      trabeculectomies (TE) and modified deep sclerectomies (mdS) in a group of
      patients with juvenile uveitic secondary glaucoma. METHODS: This is a
      retrospective analysis of 16 TE and eight mdS. RESULTS: Postoperatively, an IOP
      reduction to 11.6 +/- 4.7 mmHg was achieved in the TE group and to 18.5 +/- 11.4
      mmHg in the mdS group (p = 0.045). In the TE group, 14 patients showed
      postoperative success, one limited success and another was a failure compared to
      four successes and four failures in the mdS group (p = 0.041). The mean number of
      complications was 1.25 +/- 1.49 in the TE group and 0.38 +/- 0.74 after mdS (p =
      0.11). In the mdS group, four patients (50%) needed additional glaucoma surgery
      compared to one TE patient (p = 0.023). CONCLUSION: Both surgical techniques
      showed a marked reduction of IOP. Trabeculectomy has a higher probability of
      achieving success and lowering IOP.

PMID- 21901288
TI  - Chronic Akt activation accentuates aging-induced cardiac hypertrophy and
      myocardial contractile dysfunction: role of autophagy.
AB  - Aging is often accompanied with geometric and functional changes in the heart,
      although the underlying mechanisms remain unclear. Recent evidence has described
      a potential role of Akt and autophagy in aging-associated organ deterioration.
      This study was to examine the impact of cardiac-specific Akt activation on aging
      induced cardiac geometric and functional changes and underlying mechanisms
      involved. Cardiac geometry, contractile and intracellular Ca(2+) properties were
      evaluated using echocardiography, edge-detection and fura-2 techniques. Level of
      insulin signaling and autophagy was evaluated by western blot. Our results
      revealed cardiac hypertrophy (enlarged chamber size, wall thickness, myocyte
      cross-sectional area), fibrosis, decreased cardiac contractility, prolonged
      relengthening along with compromised intracellular Ca(2+) release and clearance
      in aged (24-26 month-old) mice compared with young (3-4 month-old) mice, the
      effects of which were accentuated by chronic Akt activation. Aging enhanced Akt
      and mTOR phosphorylation while reducing that of PTEN, AMPK and ACC with a more
      pronounced response in Akt transgenic mice. GSK3beta phosphorylation and eNOS
      levels were unaffected by aging or Akt overexpression. Levels of beclin-1, Atg5
      and LC3-II-to-LC3-I ratio were decreased in aged hearts, the effect of which with
      the exception of Atg 5 was exacerbated by Akt overactivation. Levels of p62 were
      significantly enhanced in aged mice with a more pronounced increase in Akt mice.
      Neither aging nor Akt altered beta-glucuronidase activity and cathepsin B
      although aging reduced LAMP1 level. In addition, rapamycin reduced aging-induced
      cardiomyocyte contractile and intracellular Ca(2+) dysfunction while Akt
      activation suppressed autophagy in young but not aged cardiomyocytes. In
      conclusion, our data suggest that Akt may accentuate aging-induced cardiac
      geometric and contractile defects through a loss of autophagic regulation.

PMID- 21901289
TI  - Mesenchymal stromal cells mediate a switch to alternatively activated
      monocytes/macrophages after acute myocardial infarction.
AB  - Given the established anti-inflammatory properties of mesenchymal stromal cells
      (MSCs), we investigated their effect on inflammatory cell infiltration of
      ischemic cardiac tissue and cardiac function. We employed two types of MSCs,
      human bone marrow-derived (BM) MSCs and human umbilical cord perivascular cells
      in an experimental acute myocardial infarction (MI) model with the immune
      deficient NOD/SCID gamma null mouse. Cells were infused 48 h after induction of
      MI and mice assessed 24 h later (72 h after MI) for bone marrow (BM), circulating
      and cardiac tissue-infiltrating monocytes/macrophages. We showed that in the
      presence of either MSC type, overall macrophage/monocyte levels were reduced,
      including pro-inflammatory M1-type macrophages, while the proportion of
      alternatively activated M2-type macrophages was significantly increased in the
      circulation and heart but not the BM. Moreover, we found decreased expression of
      IL-1beta and IL-6, increased IL-10 expression and fewer apoptotic cardiomyocytes
      without changes in angiogenesis in the infarct area. Fractional shortening was
      enhanced 2 weeks after cell infusion but was similar to medium controls 16 weeks
      after MI. In vitro studies showed that BM MSCs increased the frequency of
      alternatively activated monocytes/macrophages, in part by MSC-mediated secretion
      of IL-10. Our data suggest a new mechanism for MSC-mediated enhancement of
      cardiac function, possibly via an IL-10 mediated switch from infiltration of pro
      inflammatory to anti-inflammatory macrophages at the infarct site. Additional
      studies are warranted confirming the role of IL-10 and augmenting the anti
      inflammatory effects of MSCs in cardiac regeneration.

PMID- 21901290
TI  - K201 (JTV-519) alters the spatiotemporal properties of diastolic Ca(2+) release
      and the associated diastolic contraction during beta-adrenergic stimulation in
      rat ventricular cardiomyocytes.
AB  - K201 has previously been shown to reduce diastolic contractions in vivo during
      beta-adrenergic stimulation and elevated extracellular calcium concentration
      ([Ca(2+)](o)). The present study characterised the effect of K201 on electrically
      stimulated and spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca(2+)
      release and contractile events in isolated rat cardiomyocytes during beta
      adrenergic stimulation and elevated [Ca(2+)](o). Parallel experiments using
      confocal microscopy examined spontaneous diastolic Ca(2+) release events at an
      enhanced spatiotemporal resolution. 1.0 MUmol/L K201 in the presence of 150
      nmol/L isoproterenol (ISO) and 4.75 mmol/L [Ca(2+)](o) significantly decreased
      the amplitude of diastolic contractions to ~16% of control levels. The stimulated
      free Ca(2+) transient amplitude was significantly reduced, but stimulated cell
      shortening was not significantly altered. When intracellular buffering was taken
      into account, K201 led to an increase in action potential-induced SR Ca(2+)
      release. Myofilament sensitivity to Ca(2+) was not changed by K201. Confocal
      microscopy revealed diastolic events composed of multiple Ca(2+) waves (2-3)
      originating at various points along the cardiomyocyte length during each
      diastolic period. 1.0 MUmol/L K201 significantly reduced the (a) frequency of
      diastolic events and (b) initiation points/diastolic interval in the remaining
      diastolic events to 61% and 71% of control levels respectively. 1.0 MUmol/L K201
      can reduce the probability of spontaneous diastolic Ca(2+) release and their
      associated contractions which may limit the propensity for the contractile
      dysfunction observed in vivo.

PMID- 21901291
TI  - Estradiol inhibits hyaluronic acid synthase 1 expression in human vascular smooth
      muscle cells.
AB  - Epidemiological and clinical data suggest that estrogen retards the progression
      of atherosclerosis. This study aims to elucidate whether the phenotypic
      regulation of human vascular smooth muscle cells (VSMC) by estrogen may involve
      effects on the hyaluronan matrix. VSMC were synchronized by serum withdrawal and
      subsequently stimulated with 0.001, 0.01, 0.1 and 1 MUM estradiol (E(2)) in the
      presence or absence of platelet-derived growth factor BB (PDGF-BB) for 24 h. E(2)
      reduced mRNA-expression of hyaluronic acid synthase (HAS) 1 in the presence and
      absence of PDGF-BB. In contrast, HAS2- and HAS3-mRNA-expression were not
      affected. This E(2)-mediated effect on HAS1 mRNA-expression was accompanied by
      reduced hyaluronan secretion and a shift of HA toward lower molecular weight as
      evidenced by molecular sieve chromatography. The downregulation of HAS1 was
      abrogated by the estrogen receptor (ER) alpha and beta antagonist ICI182780 and
      could be mimicked by the ERalpha-agonist propyl-pyrazole triol (PPT). On the
      contrary, the ERbeta-agonist diarylpropionitrile (DPN) had no effect on HAS1 mRNA
      expression. To investigate whether the downregulation of HAS1 was causally
      involved in the phenotypic regulation of human VSMC by E(2), lentiviral
      overexpression of HAS1 was conducted. Overexpression of HAS1 abrogated the
      inhibition of sustained ERK1/2 phosphorylation and in turn inhibition of DNA
      synthesis by E(2). For the first time this study provides strong evidence that
      HAS1-driven HA-synthesis is a target of E(2) in human VSMC and that E(2) mediates
      part of its anti-proliferative effects through an ERalpha-dependent inhibition of
      HA-synthesis.

PMID- 21901292
TI  - Comparative study of fungal cell disruption--scope and limitations of the
      methods.
AB  - Simple and effective protocols of cell wall disruption were elaborated for tested
      fungal strains: Penicillium citrinum, Aspergillus fumigatus, Rhodotorula
      gracilis. Several techniques of cell wall disintegration were studied, including
      ultrasound disintegration, homogenization in bead mill, application of chemicals
      of various types, and osmotic shock. The release of proteins from fungal cells
      and the activity of a cytosolic enzyme, glucose-6-phosphate dehydrogenase, in the
      crude extracts were assayed to determine and compare the efficacy of each method.
      The presented studies allowed adjusting the particular method to a particular
      strain. The mechanical methods of disintegration appeared to be the most
      effective for the disintegration of yeast, R. gracilis, and filamentous fungi, A.
      fumigatus and P. citrinum. Ultrasonication and bead milling led to obtaining
      fungal cell-free extracts containing high concentrations of soluble proteins and
      active glucose-6-phosphate dehydrogenase systems.

PMID- 21901293
TI  - Isolation and characterization of Clostridium difficile from shellfish and marine
      environments.
AB  - This pilot study was carried out to evaluate the occurrence of Clostridium
      difficile in marine environments and in edible shellfish. Samples of seawater,
      sediment, and zooplankton were collected at five sampling stations in the Gulf of
      Naples. Six samples of edible shellfish, furthermore, were obtained: two from
      mussel farms and four from wholesalers. The isolation and the characterization of
      C. difficile strains were carried out using selective media and molecular
      techniques, respectively. C. difficile was isolated from nine of the 21 samples
      investigated. Shellfish and zooplankton showed the highest prevalence of positive
      samples. No C. difficile was detected in marine sediment. Majority of the C.
      difficile isolates were toxin A/B positive. Six known different PCR ribotypes
      (003, 005, 009, 010, 056, and 066) were identified, whereas one strain may
      represent a new PCR ribotype. C. difficile may be present in the marine
      environment in Southern Italy, including shellfish and zooplankton. This study is
      reporting the isolation of C. difficile from zooplankton, clams, and mussels and
      pointing out a new possible route to exposure to C. difficile of healthy
      individuals in the community.

PMID- 21901294
TI  - Phylogenetic diversity of bacterial communities in bovine rumen as affected by
      diets and microenvironments.
AB  - Phylogenetic analysis was conducted to examine ruminal bacteria in two ruminal
      fractions (adherent fraction vs. liquid fraction) collected from cattle fed with
      two different diets: forage alone vs. forage plus concentrate. One hundred forty
      four 16S rRNA gene (rrs) sequences were obtained from clone libraries constructed
      from the four samples. These rrs sequences were assigned to 116 different
      operational taxonomic units (OTUs) defined at 0.03 phylogenetic distance. Most of
      these OTUs could not be assigned to any known genus. The phylum Firmicutes was
      represented by approximately 70% of all the sequences. By comparing to the OTUs
      already documented in the rumen, 52 new OTUs were identified. UniFrac, SONS, and
      denaturing gradient gel electrophoresis analyses revealed difference in diversity
      between the two fractions and between the two diets. This study showed that rrs
      sequences recovered from small clone libraries can still help identify novel
      species-level OTUs.

PMID- 21901295
TI  - Structure of a protein-detergent complex: the balance between detergent cohesion
      and binding.
AB  - Despite the major interest in membrane proteins at functional, genomic, and
      therapeutic levels, their biochemical and structural study remains challenging,
      as they require, among other things, solubilization in detergent micelles. The
      complexity of this task derives from the dependence of membrane protein structure
      on their anisotropic environment, influenced by a delicate balance between many
      different physicochemical properties. To study such properties in a small protein
      detergent complex, we used fluorescence measurements and molecular dynamics (MD)
      simulations on the transmembrane part of glycophorin A (GpAtm) solubilized in
      micelles of dihexanoylphosphatidylcholine (DHPC) detergent. Fluorescence
      measurements show that DHPC has limited ability to solubilize the peptide, while
      MD provides a possible molecular explanation for this. We observe that the
      detergent molecules are balanced between two different types of interactions:
      cohesive interactions between detergent molecules that hold the micelle together,
      and adhesive interactions with the peptide. While the cohesive interactions are
      detergent mediated, the adhesion to the peptide depends on the specific
      interactions between the hydrophobic parts of the detergent and the topography of
      the peptide dictated by the amino acids. The balance between these two parameters
      results in a certain frustration of the system and rather slow equilibration.
      These observations suggest how molecular properties of detergents could influence
      membrane protein stabilization and solubilization.

PMID- 21901296
TI  - Subjective perception versus objective outcome after intravitreal ranibizumab for
      exudative AMD.
AB  - BACKGROUND: The efficacy of ranibizumab in preserving visual acuity in exudative
      age-related macular degeneration (AMD) has been widely demonstrated. However,
      statistically significant improvements in outcome measures such as best-corrected
      visual acuity (BCVA) may not necessarily be clinically relevant. Clinical
      relevance can be assumed when the treatment success is perceivable for the
      patient. We therefore investigated the relation between subjective perception of
      the treatment success and the objective outcome after intravitreal ranibizumab
      treatment. METHODS: In this prospective interventional case series, patients
      received three monthly ranibizumab injections for exudative AMD. To assess the
      subjective study outcome (SSO) 4 weeks after the third injection, patients had to
      grade the overall trend of visual quality in the treated eye since baseline.
      Objective changes of functional (BCVA measured with ETDRS reading charts; reading
      visual acuity (RVA) and reading speed measured with Radner reading charts) and
      morphological parameters (central retinal thickness measured with OCT) were
      evaluated. Agreement between SSO and objective parameters was assessed with
      nonparametric statistical tests. RESULTS: Seventy-four eyes of 74 patients were
      analyzed. Mean BCVA increased from 55 (SD +/-13) ETDRS letters by +3.16 letters
      (SD +/-11.99, p = 0.03). Mean RVA (measured as logRAD score) increased by -0.067
      (SD +/-0.294, p = 0.052). Fifty patients (68%) perceived a subjective
      improvement, 16 (21%) no change, and eight (11%) a worsening in the study eye
      (SSO). SSO was independent of whether treating the better- or worse-seeing eye (p
      = 0.83). SSO was significantly correlated with BCVA, RVA, and reading speed (as
      assessed using the critical print size (CPS)) changes (p = 0.002, p < 0.001, and
      p = 0.002), but showed no correlation to central retinal thickness changes (p =
      0.783). Patients gaining >= +5 ETDRS letters had a significantly better SSO (p =
      0.001). The rate of subjective improvement increased distinctly to >80% among
      patients gaining >= +7 letters. CONCLUSIONS: In this study, 2/3 of patients
      reported a subjective improvement from ranibizumab injections. Patients'
      perception was significantly correlated with objective changes in BCVA and
      reading visual acuity. Our data indicate that the mean threshold for perceived
      improvement is a +5 to +7 letter gain, which might accordingly be considered
      clinically meaningful and relevant. Patients' perception was independent of
      whether the better- or worse-seeing eye was treated.

PMID- 21901297
TI  - Switching from oxycodone to methadone in advanced cancer patients.
AB  - PURPOSE: The aim of this study was to prospectively evaluate the outcomes and the
      conversion ratio of switching from oxycodone to methadone in advanced cancer
      patients admitted to an acute palliative care unit. PATIENTS AND METHODS: A
      prospective study was carried out on a cohort of consecutive sample of patients
      receiving oxycodone, who were switched for different reasons mainly because of an
      inconvenient balance between analgesia and adverse effects. An initial conversion
      ratio between oxycodone and methadone was 3.3:1. Intensity of pain and symptoms
      associated with opioid therapy were recorded, and a distress score (DS) was also
      calculated as a sum of symptom intensity. A successful switching was considered
      when the intensity of pain and/or DS or the principal symptom requiring switching
      decreased at least of 33% of the value recorded before switching. RESULTS:
      Nineteen out of 542 patients admitted to the unit in 1 year underwent a switching
      from oxycodone to methadone. Almost all substitutions were successful. The
      prevalent indication for opioid switching was uncontrolled pain and adverse
      effects (12 patients). No significant changes between the initial conversion
      ratio and final conversion ratio between the two opioids were found. CONCLUSION:
      Switching from oxycodone to methadone is a reliable method to improve the opioid
      response in advanced cancer patients. A ratio of 3.3 appears to be reliable, even
      at high doses. Further studies should be performed to confirm these results in
      other settings and with very high doses of oxycodone.

PMID- 21901298
TI  - Prophylaxis of radiotherapy-induced nausea and vomiting in the palliative
      treatment of bone metastases.
AB  - PURPOSE: To document the incidence and timing of radiotherapy-induced nausea and
      vomiting (RINV) in the treatment of bone metastases among patients receiving
      prophylaxis with a 5-HT(3) receptor antagonist. METHODS: Patients receiving
      single (SF) or multiple fraction (MF) palliative radiotherapy (RT) of moderate or
      low emetogenic risk for bone metastases were prescribed prophylactic Ondansetron.
      The frequency and duration of prophylaxis and the use of rescue antiemetics were
      left to the discretion of the treating physicians. Patients documented episodes
      of nausea (N) and vomiting (V) in daily diaries before and during RT, and until
      10 days following RT completion. Rates of complete prophylaxis (CP) for N&V,
      respectively (CP = no event and no rescue medication), were calculated for the
      acute phase (the period from the start of RT to the first day following RT
      completion inclusive) and the delayed phase (the second to tenth days following
      RT completion inclusive). RESULTS: Fifty-nine patients were enrolled, and 32 were
      evaluable. CP rates were as follows: moderate-risk SF group (n = 16), acute phase
      (CP for N = 56%, CP for V = 69%) and delayed phase (CP for N = 31%, CP for V =
      44%); moderate-risk MF group (n = 7), acute phase (CP for N = 71%, CP for V =
      57%) and delayed phase (CP for N = 43%, CP for V = 57%); low-risk SF group (n =
      8), acute phase (CP for N = 50%, CP for V = 100%) and delayed phase (CP for N =
      43%, CP for V = 57%); and low-risk MF group (n = 1), acute phase (CP for N =
      100%, CP for V = 100%) and delayed phase (CP for N = 100%, CP for V = 100%).
      CONCLUSIONS: Despite prophylaxis, RINV was common among patients receiving
      palliative radiotherapy for bone metastases, especially during the delayed phase.

PMID- 21901299
TI  - The reliability and validity of the Korean version of the Pittsburgh Sleep
      Quality Index.
AB  - PURPOSE: The Pittsburgh Sleep Quality Index (PSQI) is a self-reported
      questionnaire that measures sleep quality during the previous month. The aims of
      this study were to analyze the reliability and validity of the Korean version of
      the PSQI (PSQI-K) and to evaluate its usefulness. METHODS: We developed the PSQI
      K, which involved translating the original PSQI into Korean and then translating
      back into English to check its accuracy. We tested the validity of the PSQI-K on
      a total of 394 individuals: 261 with poor sleep (primary insomnia, n = 211;
      narcolepsy, n = 50) and 133 with good sleep. All subjects completed the PSQI-K,
      285 had overnight nocturnal polysomnography, and 53 were randomly selected for a
      retest with the questionnaire after 2-4 weeks without any intervening treatment.
      The mean PSQI-K global scores in each group were analyzed after adjusting for age
      and sex. RESULTS: Cronbach's alpha coefficient for internal consistency of the
      total score of the PSQI-K was 0.84 which shows high reliability. Sensitivity and
      specificity for distinguishing poor and good sleepers were 0.943 and 0.844 using
      the best cutoff point of 8.5. The total and component scores of the PSQI-K for
      insomnia and narcolepsy were significantly higher than those for controls (p <
      0.05). The test-retest correlation coefficient was 0.65 for the total score (p <
      0.001). There was no significant difference between the two values using the
      paired t tests. CONCLUSIONS: The PSQI-K is a reliable and valid questionnaire for
      evaluating sleep quality in patients with sleep disorders.

PMID- 21901300
TI  - Significant mortality of large ruminants due to hypothermia in northern and
      central Lao PDR.
AB  - An extreme cold exposure event occurred between March 14th and 19th 2011 in
      northern and central Lao PDR resulting in a major mortality of cattle and
      buffalo. At least six northern and one central province reported losses,
      involving 46 districts and 1,384 smallholder farmers, with a total of 7,162
      cattle and 3,744 buffalo reported to have died in association with cold weather.
      Affected animals were observed to shiver, display slow and shallow respiration,
      lose consciousness and eventually die. Many deaths occurred at night and were
      recorded in both sexes and all ages of large ruminants. However, mortalities
      occurred mostly in animals that were free-grazing in the forest and natural
      grassland, and exposed to the cold weather. Some housed animals that were
      provided with warmth from shelter and fires and supplementary feed did not die.
      Samples from dead animals collected for laboratory analysis confirmed that
      bacterial or viral pathogens were not present. The cause of the mortality was
      attributed to hypothermia, and the economic losses were estimated at USD
      2,463,912.00. Xieng Khouang Province reported the most severe losses with deaths
      of 4,600 cattle and 1,665 buffalo. At Thong Haihin meteorological station in this
      province on March 16th and 17th 2011, minimum temperatures recorded were 6.7
      degrees C and 7.5 degrees C and rainfall recorded was 36.6 mm and 61.7 mm,
      respectively. This was the first reported extreme cold event in living memory
      occurring between the end of dry season and beginning of the wet season in
      northern Laos. This event is reported in detail as it caused a major loss of
      wealth for poor smallholder farmers and indicates that strategies to minimise the
      impact of extreme cold weather events need to be included in livestock
      development extension programmes.

PMID- 21901301
TI  - Estimating non-genetic and genetic parameters of pre-weaning growth traits in
      Raini Cashmere goat.
AB  - Data and pedigree information used in the present study were 3,022 records of
      kids obtained from the breeding station of Raini goat. The studied traits were
      birth weight (BW), weaning weight (WW), average daily gain from birth to weaning
      (ADG) and Kleiber ratio at weaning (KR). The model included the fixed effects of
      sex of kid, type of birth, age of dam, year of birth, month of birth, and age of
      kid (days) as covariate that had significant effects, and random effects direct
      additive genetic, maternal additive genetic, maternal permanent environmental
      effects and residual. (Co) variance components were estimated using univariate
      and multivariate analysis by WOMBAT software applying four animal models
      including and ignoring maternal effects. Likelihood ratio test used to determine
      the most appropriate models. Heritability (h(a)(2)) estimates for BW, WW, ADG,
      and KR according to suitable model were 0.12 +/- 0.05, 0.08 +/- 0.06, 0.10 +/-
      0.06, and 0.06 +/- 0.05, respectively. Estimates of the proportion of maternal
      permanent environmental effect to phenotypic variance (c(2)) were 0.17 +/- 0.03,
      0.07 +/- 0.03, and 0.07 +/- 0.03 for BW, WW, and ADG, respectively. Genetic
      correlations among traits were positive and ranged from 0.53 (BW-ADG) to 1.00 (WW
      ADG, WW-KR, and ADG-KR). The maternal permanent environmental correlations
      between BW-WW, BW-ADG, and WW-ADG were 0.54, 0.48, and 0.99, respectively.
      Results indicated that maternal effects, especially maternal permanent
      environmental effects are an important source of variation in pre-weaning growth
      trait and ignoring those in the model redound incorrect genetic evaluation of
      kids.

PMID- 21901302
TI  - Effect of supplementing crossbred Xhosa lop-eared goat castrates with Moringa
      oleifera leaves on growth performance, carcass and non-carcass characteristics.
AB  - The objective of the study was to determine the effect of supplementing Moringa
      oleifera leaves (MOL) on growth performance, carcass and non-carcass
      characteristics of crossbred Xhosa lop-eared goats. A total of 24 castrated goats
      aged 8 months, with a mean initial weight of 15.1 +/- 2.3 kg, were randomly
      divided into three diet groups with eight goats in each. The duration of the
      trial was 60 days. All goats received a basal diet of grass hay (GH) ad libitum
      and wheat bran (200 g/day each). The MOL and sunflower cake (SC) groups were fed
      additional 200 g of dried M. oleifera leaves and 170 g of SC, respectively. The
      third group (GH) did not receive any additional ration. The crude protein of MOL
      (23.75%) and SC (23.27%) were higher (P < 0.05) than that of the GH diet
      (14.08%). The attained average daily weight gain for goats fed MOL, SC and GH
      were 103.3, 101.3 and 43.3 g, respectively (P < 0.05). Higher (P < 0.05) feed
      intakes observed were in SC (491.5 g) and MOL (490.75 g) compared with GH (404.5
      g). The hot carcass weight was higher (P < 0.05) for SC (10.48 kg) and MOL (10.34
      kg) than for the GH group (8.59 kg). The dressing percentage in SC (55.8%) and
      MOL (55.1%) were higher (P < 0.05) than that of the GH (52.9%). The growth
      performance and carcass characteristics of SC and MOL goats were not different.
      Feeding MOL or SC improved the growth performance and carcass characteristics of
      goats in an almost similar way, which indicates that M. oleifera could be used as
      an alternative protein supplement in goats.

PMID- 21901303
TI  - Spacers and valved holding chambers in asthma drug delivery: how many breaths are
      needed to achieve adequate lung deposition?

PMID- 21901304
TI  - Innate immunity and the role of defensins in otitis media.
AB  - Otitis media is the most common pediatric disease in developed countries and a
      significant cause of morbidity and hearing loss in developing countries. The
      innate immune system is essential to protecting the middle ear from infection.
      Defensins, broad-spectrum cationic antimicrobial peptides, have been implicated
      in prevention of and the early response to acute otitis media; however, the
      mechanisms by which defensins and other antimicrobial molecules mediate this
      protection have not been completely elucidated. In both animal otitis media
      models and human middle ear epithelial cell culture models, beta-defensins are
      highly induced and effectively kill the common pathogens associated with otitis
      media. We review the importance of innate immunity in protecting the middle ear
      and recent advances in understanding the roles of defensins and other
      antimicrobial molecules in the prevention and treatment of otitis media. The
      extremely high prevalence of otitis media, in spite of sophisticated innate and
      adaptive immune systems, is a vexing problem for clinicians and scientists. We
      therefore also review mechanisms by which bacteria evade innate immune defenses.

PMID- 21901305
TI  - Should newborns be screened for immunodeficiency?: lessons learned from infants
      with recurrent otitis media.
AB  - Recurrent otitis media in children is considered one of the warning signs of
      primary immunodeficiencies (PIDs), particularly antibody deficiencies. Infants
      who have the most serious and potentially lethal form of PID, severe combined
      immunodeficiency (SCID), sometimes present with recurrent otitis media. Most of
      the time, because of the severity of the immune defect, they develop more serious
      and systemic infections. SCID is distinct among the PIDs and considered a
      pediatric emergency. Diagnosing SCID during the newborn period is crucial because
      survival completely depends on early diagnosis and treatment. Mortality declines
      significantly if immune reconstitution is established before 3.5 months of age,
      particularly before severe infections have occurred. However, most patients are
      diagnosed after they have suffered chronic or recurrent infections and developed
      permanent sequelae. Without institution of population-based newborn screening,
      most infants will miss the opportunity to live a healthy life.

PMID- 21901306
TI  - Oral food challenges in children: review and future perspectives.
AB  - Food allergy is a lifelong condition with no known treatment or cure. Allergy
      tests such as skin tests and blood tests are not always accurate when positive
      and are not necessarily diagnostic of a food allergy. A food allergy takes into
      consideration both the history of exposure and the testing. The food challenge is
      considered the diagnostic gold standard for food allergy. However, recent
      evidence suggests that not enough challenges are being performed. Several
      techniques exist with which clinicians can challenge patients. Providers who
      perform challenges should be familiar with assessing signs and symptoms of a
      potential reaction and must be prepared to treat anaphylaxis. The magnitude of
      the serum and skin tests may be of assistance in stratifying a patient's risk of
      passing a challenge, and newer diagnostic tests may help better stratify such
      risk of based on particular epitope recognition.

PMID- 21901308
TI  - Determination of radioactive elements and heavy metals in sediments and soil from
      domestic water sources in northern peninsular Malaysia.
AB  - Soil serves as a major reservoir for contaminants as it posseses an ability to
      bind various chemicals together. To safeguard the members of the public from an
      unwanted exposure, studies were conducted on the sediments and soil from water
      bodies that form the major sources of domestic water supply in northern
      peninsular Malaysia for their trace element concentration levels. Neutron
      Activation Analysis, using Nigeria Research Reactor-1 (NIRR-1) located at the
      Centre for Energy Research and Training, Zaria, Nigeria was employed as the
      analytical tool. The elements identified in major quantities include Na, K, and
      Fe while As, Br, Cr, U, Th, Eu, Cs, Co, La, Sm, Yb, Sc, Zn, Rb, Ba, Lu, Hf, Ta,
      and Sb were also identified in trace quantities. Gamma spectroscopy was also
      employed to analyze some soil samples from the same area. The results indicated
      safe levels in terms of the radium equivalent activity, external hazard index as
      well as the mean external exposure dose rates from the soil. The overall
      screening of the domestic water sources with relatively high heavy metals
      concentration values in sediments and high activity concentration values in soil
      is strongly recommended as their accumulation overtime as a consequence of
      leaching into the water may be of health concern to the members of the public.

PMID- 21901307
TI  - Calcium supplementation modulates arsenic-induced alterations and augments
      arsenic accumulation in callus cultures of Indian mustard (Brassica juncea (L.)
      Czern.).
AB  - In the present study, the effect of arsenate (AsV) exposure either alone or in
      combination with calcium (Ca) was investigated in callus cultures of Brassica
      juncea (L.) Czern. cv. Pusa Bold grown for a period up to 24 h. The AsV (250 MUM)
      + Ca (10 mM) treatment resulted in a significantly higher level of As (464 MUg g(
      1) dry weight (DW)) than AsV without Ca (167 MUg g(-1) DW) treatment at 24 h.
      Furthermore, AsV + Ca-treated calli had a higher percent of AsIII (24-47%) than
      calli subjected to AsV treatment (12-14%). Despite this, AsV + Ca-treated calli
      did not show any signs of hydrogen peroxide (H(2)O(2)) accumulation or cell death
      upon in vivo staining, while AsV-exposed calli had increased H(2)O(2), shrinkage
      of cytoplasmic contents, and cell death. Thus, AsV treatment induced oxidative
      stress, which in turn elicited a response of antioxidant enzymes and metabolites
      as compared with control and AsV + Ca treatment. The positive effects of Ca
      supplementation were also correlated to an increase in thiolic constituents',
      viz., cysteine, reduced glutathione, and glutathione reductase in AsV + Ca than
      in AsV treatment. An analysis of selected signaling related genes, e.g., mitogen
      activated protein kinases (MAPK3 and MAPK6) and jasmonate ZIM-domain (JAZ3)
      suggested that AsV and AsV + Ca followed variable pathways to sense and signal
      the As stress. In AsV-alone treatment, jasmonate signaling was seemingly
      activated, while MAPK3 was not involved. In contrast, AsV + Ca treatment appeared
      to specifically inhibit jasmonate signaling and activate MAPK3. In conclusion, Ca
      supplementation may hold promise for achieving increased As accumulation in
      plants without compromising their tolerance.

PMID- 21901309
TI  - Natural resources assessment and their utilization: analyses from a Himalayan
      state.
AB  - The present paper quantifies and reviews the natural resource use in the
      Himalayan state of Himachal Pradesh (HP). Twenty-five percent of the geographical
      area of HP is under forests and harbour ca. 3,400 plant species. The available
      bioresources not only support the livelihood of nearly 6 million people but also
      fulfill the forage requirement of 5.2 million livestock. Thus, dependence on
      bioresources is manifold. Based on field surveys to different localities of HP
      and analyses of published information, two types of resource use patterns have
      been identified. One, the direct use of forest resources which is represented by
      extraction of timber, fuelwood and fodder; and the second represents indirect
      resource use from the forest that is represented by activities related to
      agriculture, tourism and industry. Amongst the direct resource use, annual timber
      requirement of the local people works out to be 310,063 m(3). On the other hand,
      annual fuelwood and fodder requirement of local people is to the tune of
      3,646,348.8 and 10,294,116.5 tons, respectively. Extraction of fodder therefore
      appears to be one of the main reasons for forest degradation in HP as opposed to
      timber and fuelwood extraction. However, compared to direct resource use,
      indirect resource use and pressures have far more pronounced effect on the
      forests. Of the indirect pressures, shifts in agriculture patterns and increased
      tourism seem to be the most prominent.

PMID- 21901310
TI  - Integrating geospatial and ground geophysical information as guidelines for
      groundwater potential zones in hard rock terrains of south India.
AB  - The increasing demand of water has brought tremendous pressure on groundwater
      resources in the regions were groundwater is prime source of water. The objective
      of this study was to explore groundwater potential zones in Maheshwaram watershed
      of Andhra Pradesh, India with semi-arid climatic condition and hard rock granitic
      terrain. GIS-based modelling was used to integrate remote sensing and geophysical
      data to delineate groundwater potential zones. In the present study, Indian
      Remote Sensing RESOURCESAT-1, Linear Imaging Self-Scanner (LISS-4) digital data,
      ASTER digital elevation model and vertical electrical sounding data along with
      other data sets were analysed to generate various thematic maps, viz.,
      geomorphology, land use/land cover, geology, lineament density, soil, drainage
      density, slope, aquifer resistivity and aquifer thickness. Based on this
      integrated approach, the groundwater availability in the watershed was classified
      into four categories, viz. very good, good, moderate and poor. The results reveal
      that the modelling assessment method proposed in this study is an effective tool
      for deciphering groundwater potential zones for proper planning and management of
      groundwater resources in diverse hydrogeological terrains.

PMID- 21901311
TI  - Assessing the potential impact of fly ash amendments on Indian paddy field with
      special emphasis on growth, yield, and grain quality of three rice cultivars.
AB  - Proper disposal and/or recycling of different industrial waste materials have
      long been recognized as a prime environmental concern throughout the world, and
      fly ash is major amongst them. In the present study, we tried to assess the
      feasibilities of possible effective and safe utilization of fly ash as soil
      amendment in Indian paddy field and its impact on rice plants, especially at
      growth and yield level. Our results showed that certain doses of fly ash
      amendments have significantly improved the physico-chemical and mineralogical
      properties of paddy field soil, and at lower level of amendments, fly ash induced
      the growth performances of three rice cultivars too. Grain yield and grain
      quality also responded similarly as per the growth responses. However,
      differential cultivar response was observed accordingly, and cultivar Sugandha-3
      showed higher yield as compared with cultivars Sambha and Saryu-52. Based on the
      observed results, it was concluded that up to a certain level, fly ash amendments
      could be beneficial for Indian paddy field and can be utilized as feasible
      management strategy for the disposal of this major industrial waste.

PMID- 21901312
TI  - Prioritizing organic chemicals for long-term air monitoring by using empirical
      monitoring data--application to data from the Swedish screening program.
AB  - This paper illustrates a step-by-step approach for evaluating chemical monitoring
      data in air and deposition and for prioritizing chemicals to be included in long
      term air monitoring programs. The usability of the method is shown by application
      to data generated within the Swedish screening program. The suggested
      prioritization approach uses a novel methodology by combining empirical data on
      occurrence in air and deposition with publicly available quantitative structure
      activity relationship estimation tools that predict atmospheric persistence and
      bioaccumulation. A selection tree is presented, which may be used by regulatory
      bodies to prioritize chemicals for long-term air monitoring. A final ranking list
      is presented proposing a prioritization order for inclusion in monitoring
      programs. Based on the suggested strategy, the chemicals identified as most
      relevant to include in Swedish long-term monitoring programs were short-chain
      chlorinated paraffins(C10-C13), perfluorooctane sulfonate, octachlorostyrene,
      hexabromocyclododecane, hexachlorobenzene, pentachloroanisole,
      decamethylcyclopentasiloxane, octamethylcyclotetrasiloxane, pentachlorobenzene,
      1,2,3,4-tetrachlorobenzene, hexachlorobutadiene, dodecamethylcyclohexasiloxane,
      perfluorodecane sulfonate, 1,2,4,5-tetrachlorobenzene, and pentabromophenol.

PMID- 21901313
TI  - The inability of tegaserod to affect platelet aggregation and coronary artery
      tone at supratherapeutic concentrations.
AB  - In 2007, the results from a meta analysis of 29 clinical studies indicated that
      tegaserod (Zelnorm(r)), a 5-hydroxytryptamine(4) (5-HT(4)) receptor agonist with
      gastrointestinal prokinetic activity, was associated with an increased incidence
      of cardiovascular ischemic events, resulting in its withdrawal from many markets
      around the world. Stimulation of platelet aggregation has been proposed to
      explain the phenomenon. However, data from recent epidemiological studies have
      suggested that there is no correlation between tegaserod use and the incidence of
      cardiovascular ischemia. In this study, the influence of tegaserod, at
      concentrations up to tenfold higher than the total plasma C (max) for the 6 mg
      clinical dose, has been investigated on platelet aggregation under standard
      conditions with platelet-rich plasma (PRP) obtained from healthy human subjects.
      Additionally, the influence of tegaserod on coronary artery tone was evaluated as
      an alternative pro-ischemic mechanism. The positive control, thrombopoietin, but
      not tegaserod, demonstrated a statistically significant increase in platelet
      aggregation using the same PRP samples with either adenosine diphosphate (ADP) or
      ADP plus 5-HT as an aggregation agonist. Tegaserod had no contractile activity in
      either porcine or human isolated coronary artery preparations, and only a small
      and variable response in canine coronary arteries at concentrations higher than
      those achieved clinically. Taken together, these studies do not identify a
      mechanism for the ischemic events that have been attributed to tegaserod in
      humans.

PMID- 21901314
TI  - Role of beta3-adrenoceptors in regulation of retinal vascular tone in rats.
AB  - The aim of this study was to determine the role of beta(3)-adrenoceptors in the
      action of endogenous catecholamines (adrenaline and noradrenaline) on rat retinal
      arterioles in vivo. Using an original high-resolution digital fundus camera, the
      rat ocular fundus images were captured. The diameter of retinal arterioles
      contained in the images was measured. Both systemic blood pressure and heart rate
      were recorded continuously. Adrenaline (0.3-5.0 MUg/kg/min, i.v.) increased the
      diameter of retinal arterioles, mean blood pressure and heart rate in a dose
      dependent manner. Under blockade of beta(1)/beta(2)-adrenoceptors with
      propranolol (2 mg/kg, i.v. bolus followed by 100 MUg/kg/min infusion), adrenaline
      decreased the diameter of retinal arterioles. Similar observation was made under
      treatment with the beta(3)-adrenoceptor antagonist L-748337 (50 MUg/kg, i.v.).
      The pressor response to adrenaline was enhanced by propranolol, but not by L
      748337. The positive chronotropic action of adrenaline was markedly prevented by
      propranolol, whereas it was unaffected by L-748337. Noradrenaline (0.03-1.0
      MUg/kg/min, i.v.) decreased the diameter of retinal arterioles but increased the
      mean blood pressure and heart rate. The effects of noradrenaline on retinal
      arteriolar diameter and blood pressure were unaffected by propranolol or L
      748337. The positive chronotropic action of noradrenaline was almost completely
      abolished by propranolol. These results suggest that beta(3)-adrenoceptors play
      crucial roles in vasodilator responses to adrenaline of retinal arterioles but
      have minor or no effect on noradrenaline-induced responses. The results also
      indicate that the functional role of beta(3)-adrenoceptors may be more important
      than that in peripheral resistance vessels.

PMID- 21901315
TI  - Agents increasing cyclic GMP amplify 5-HT4-elicited positive inotropic response
      in failing rat cardiac ventricle.
AB  - Activation of 5-HT(4) receptors in failing ventricles elicits a cAMP-dependent
      positive inotropic response which is mainly limited by the cGMP-inhibitable
      phosphodiesterase (PDE) 3. However, PDE4 plays an additional role which is
      demasked by PDE3 inhibition. The objective of this study was to evaluate the
      effect of cGMP generated by particulate and soluble guanylyl cyclase (GC) on the
      5-HT(4)-mediated inotropic response. Extensive myocardial infarctions were
      induced by coronary artery ligation in Wistar rats, exhibiting heart failure 6
      weeks after surgery. Contractility was measured in left ventricular preparations.
      Cyclic GMP was measured by EIA. In ventricular preparations, ANP or BNP displayed
      no impact on 5-HT(4)-mediated inotropic response. However, CNP increased the 5
      HT(4)-mediated inotropic response as well as the beta(1)-adrenoceptor (beta(1)
      AR)-mediated response to a similar extent as PDE3 inhibition by cilostamide.
      Pretreatment with cilostamide eliminated the effect of CNP. Inhibition of nitric
      oxide (NO) synthase and soluble GC by L-NAME and ODQ, respectively, attenuated
      the 5-HT(4)-mediated inotropic response, whereas the NO donor Sin-1 increased
      this response. The effects were absent during PDE3 inhibition, suggesting cGMP
      dependent inhibition of PDE3. However, in contrast to the effects on the 5-HT(4)
      response, Sin-1 inhibited whereas L-NAME and ODQ enhanced the beta(1)-AR-mediated
      inotropic response. cGMP generated both by particulate (NPR-B) and soluble GC
      increases the 5-HT(4)-mediated inotropic response in failing hearts, probably
      through inhibition of PDE3. beta(1)-AR and 5-HT(4) receptor signalling are
      subject to opposite regulatory control by cGMP generated by soluble GC in failing
      hearts. Thus, cGMP from different sources is functionally compartmented, giving
      differential regulation of different G(s)-coupled receptors.

PMID- 21901316
TI  - Acute and post-acute behavioral and psychological effects of salvinorin A in
      humans.
AB  - RATIONALE: Salvia divinorum has been used for centuries, and nontraditional use
      in modern societies is increasing. Inebriation and aftereffects of use are poorly
      documented in the scientific literature. OBJECTIVES: This double-blind, placebo
      controlled, randomized study analyzed subjective experiences of salvinorin A (SA)
      inebriation and consequences of use after 8 weeks. METHODS: Thirty middle-aged,
      well-educated, hallucinogen-experienced participants smoked either 1,017 or 100
      MUg SA 2 weeks apart in counterbalanced order. Vital signs were recorded before
      and after inhalation. A researcher rated participants' behavior during sessions.
      Participants completed the Hallucinogen Rating Scale (HRS) assessing inebriation
      immediately after each session. Differences were analyzed between groups as
      functions of dose and time. After 8 weeks, participants were interviewed to
      determine reported consequences and aftereffects. RESULTS: Participants talked,
      laughed, and moved more often on an active dose. All six HRS clusters were
      significantly elevated on an active dose indicating hallucinogenic experiences.
      No significant adverse events were observed or reported by participants.
      CONCLUSIONS: The present results indicate similarities as well as differences
      between the subjective effects of S. divinorum and other hallucinogens. As a
      selective kappa opioid receptor agonist, SA may be useful for expanding
      understanding of the psychopharmacology and psychology of hallucinogenic states
      beyond serotonergic mechanisms.

PMID- 21901317
TI  - Escitalopram, an antidepressant with an allosteric effect at the serotonin
      transporter--a review of current understanding of its mechanism of action.
AB  - RATIONALE: Escitalopram is a widely used antidepressant for the treatment of
      patients with major depression. It is the pure S-enantiomer of racemic
      citalopram. Several clinical trials and meta-analyses indicate that escitalopram
      is quantitatively more efficacious than many other antidepressants with a faster
      onset of action. OBJECTIVE: This paper reviews current knowledge about the
      mechanism of action of escitalopram. RESULTS: The primary target for escitalopram
      is the serotonin transporter (SERT), which is responsible for serotonin (or 5
      hydroxytryptamine [5-HT]) reuptake at the terminals and cell bodies of
      serotonergic neurons. Escitalopram and selective serotonin reuptake inhibitors
      bind with high affinity to the 5-HT binding site (orthosteric site) on the
      transporter. This leads to antidepressant effects by increasing extracellular 5
      HT levels which enhance 5-HT neurotransmission. SERT also has one or more
      allosteric sites, binding to which modulates activity at the orthosteric binding
      site but does not directly affect 5-HT reuptake by the transporter. In vitro
      studies have shown that through allosteric binding, escitalopram decreases its
      own dissociation rate from the orthosteric site on the SERT. R-citalopram, the
      nontherapeutic enantiomer in citalopram, is also an allosteric modulator of SERT
      but can inhibit the actions of escitalopram by interfering negatively with its
      binding. Both nonclinical studies and some clinical investigations have
      demonstrated the cellular, neurochemical, neuroadaptive, and neuroplastic changes
      induced by escitalopram with acute and chronic administration. CONCLUSIONS: The
      findings from binding, neurochemical, and neurophysiological studies may provide
      a mechanistic rationale for the clinical difference observed with escitalopram
      compared to other antidepressant therapies.

PMID- 21901318
TI  - Role of calcineurin in the VTA in rats behaviorally sensitized to
      methamphetamine.
AB  - RATIONALE: Chronic psychostimulant administration increases locomotor activity,
      which is referred to as locomotor sensitization. Calcineurin has been suggested
      to participate in psychostimulant-induced sensitization, but the underlying
      neurobiological mechanism is poorly understood. OBJECTIVES: This study was
      designed to examine whether calcineurin activity and its substrates participate
      in methamphetamine (METH)-induced locomotor sensitization in rats. MATERIALS AND
      METHODS: Two weeks daily METH (1 mg/kg, i.p.) was administrated to rats to induce
      locomotor sensitization, activity of calcineurin and its substrates Synapsin and
      glycogen synthase kinase-3beta (GSK-3beta) were detected. The initiation and
      expression of locomotor sensitization were tested by inhibition of calcineurin
      activity systematically or locally in the ventral tegmental area (VTA). RESULTS:
      Expression of the calcineurin A subunit (catalytic subunit) increased in the VTA
      but not prefrontal cortex, nucleus accumbens, or hippocampus in rats sensitized
      to METH. The calcineurin inhibitor cyclosporine A, systemically administered or
      microinfused into the VTA, suppressed the initiation but not expression of METH
      induced locomotor sensitization. Chronic METH exposure upregulated the expression
      of the calcineurin A subunit in the VTA, which was negatively associated with
      downregulation of the phosphorylation of Synapsin and GSK-3beta. Moreover, the
      related molecular changes were blocked by systemically administered cyclosporine
      A or microinjections into the VTA. CONCLUSIONS: These data elucidate the critical
      role of calcineurin in the neurobiological mechanism underlying METH-induced
      locomotor sensitization, suggesting that calcineurin might participate in the
      initiation of METH-induced locomotor sensitization by negatively regulating the
      activity of Synapsin and GSK-3beta in the VTA.

PMID- 21901319
TI  - D1 receptor activation improves vigilance in rats as measured by the 5-choice
      continuous performance test.
AB  - RATIONALE: Impaired attention/vigilance is putatively core to schizophrenia. The
      dopaminergic D(1) receptor system has been reported as one of the most promising
      targets for improving cognition in patients with schizophrenia, with some
      evidence suggesting D(1) activation may improve sustained attention. OBJECTIVES:
      The purpose of this study was twofold: firstly assessing the applicability of
      using rats in the 5-Choice Continuous Performance Test (5 C-CPT), recently
      validated in mice. Secondly, the effect of systemic administration of a D(1)
      partial agonist, SKF 38393, on task performance during baseline, and a challenge
      session consisting of a reduced event-rate was investigated. METHODS: Animals
      were trained to perform the 5 C-CPT with performance assessed following systemic
      SKF 38393 (2, 4 and 6 mg/kg) vs. vehicle administration. RESULTS: Rats could
      discriminate between target (requiring a response) and non-target (requiring the
      inhibition of response) trials within the 5 C-CPT. Moreover, SKF 38393 treatment
      impaired performance during the baseline session reducing target detection, yet
      improved performance during the reduced event-rate challenge session, increasing
      target detection and improving signal discrimination indicating an SKF 38393
      induced enhancement of vigilance. Thus, these data suggest that activation of the
      D(1) system affected 5 C-CPT performance in a baseline dependent manner.
      CONCLUSION: Rats can be trained to perform the 5 C-CPT, appropriately withholding
      from responding to non-target trials. Systemic administration of SKF 38393
      impaired performance during baseline conditions. Following a task-related
      challenge, which reduced the event rate, activation of the dopamine (DA) D(1)
      system improved performance by heightening the animals' vigilance levels,
      quantified using signal detection theory.

PMID- 21901320
TI  - The scopolamine model as a pharmacodynamic marker in early drug development.
AB  - RATIONALE: Drug development is a high-risk and high failure enterprise, and
      studies that provide an early read on the pharmacodynamic activity of novel
      compounds could save time and money, increasing the efficiency of the drug
      development process. OBJECTIVE: Preclinical and clinical experiments were
      designed to examine the utility of the scopolamine-induced cognitive impairment
      model in predicting pharmacodynamic signals of putatively procognitive compounds,
      utilizing the acetylcholinesterase inhibitor donepezil for illustration.
      METHODS/RESULTS: In normal healthy rats, scopolamine (0.3 mg/kg) significantly
      impaired performance on the two-platform water maze and on the T-maze. The
      deficits in water maze performance were reversed by donepezil at 0.5 and 1.0
      mg/kg. There was a trend towards reversal of scopolamine-induced deficits in
      performance on the T-maze with 1.0 mg/kg donepezil. In normal healthy humans,
      scopolamine (0.3 and 0.5 mg) reliably impaired performance on the Cognitive Drug
      Research test battery composite scores (power of attention, continuity of
      attention, quality of working memory, quality of episodic secondary memory, and
      speed of memory) in a dose- and time-dependent manner. Donepezil (10 mg)
      significantly attenuated the scopolamine-induced impairment in cognition on power
      of attention, continuity of attention, quality of working memory, and speed of
      memory. CONCLUSIONS: These findings suggest that reversal of scopolamine-induced
      cognitive impairment is a viable model for predicting pharmacodynamic signals of
      procognitive compounds in both animals and humans. The utility of the scopolamine
      induced cognitive impairment model is discussed and illustrated at various
      decision points in drug development, with a focus on Go/No Go decisions.

PMID- 21901321
TI  - Alpha7-nicotinic receptors modulate nicotine-induced reinforcement and
      extracellular dopamine outflow in the mesolimbic system in mice.
AB  - RATIONALE: Nicotine is the main addictive component of tobacco and modifies brain
      function via its action on neuronal acetylcholine nicotinic receptors (nAChRs).
      The mesolimbic dopamine (DA) system, where neurons of the ventral tegmental area
      (VTA) project to the nucleus accumbens (ACb), is considered a core site for the
      processing of nicotine's reinforcing properties. However, the precise subtypes of
      nAChRs that mediate the rewarding properties of nicotine and that contribute to
      the development of addiction remain to be identified. OBJECTIVES: We investigated
      the role of the nAChRs containing the alpha7 nicotinic subunit (alpha7 nAChRs) in
      the reinforcing properties of nicotine within the VTA and in the nicotine-induced
      changes in ACb DA outflow in vivo. METHODS: We performed intra-VTA self
      administration and microdialysis experiments in genetically modified mice lacking
      the alpha7 nicotinic subunit or after pharmacological blockade of alpha7 nAChRs
      in wild-type mice. RESULTS: We show that the reinforcing properties of nicotine
      within the VTA are lower in the absence or after pharmacological blockade of
      alpha7 nAChRs. We also report that nicotine-induced increases in ACb DA
      extracellular levels last longer in the absence of these receptors, suggesting
      that alpha7 nAChRs regulate the action of nicotine on DA levels over time.
      CONCLUSIONS: The present results reveal new insights for the role of alpha7
      nAChRs in modulating the action of nicotine within the mesolimbic circuit. These
      receptors appear to potentiate the reinforcing action of nicotine administered
      into the VTA while regulating its action over time on DA outflow in the ACb.

PMID- 21901322
TI  - Quality assessment for processed and sterilized bone using Raman spectroscopy.
AB  - To eliminate the potential for infection, many tissue banks routinely process and
      terminally sterilize allografts prior to transplantation. A number of techniques,
      including the use of scanning electron microscopy, bone graft models, and
      mechanical property tests, are used to evaluate the properties of allograft bone.
      However, as these methods are time consuming and often destroy the bone sample,
      the quality assessment of allograft bones are not routinely performed after
      processing and sterilization procedures. Raman spectroscopy is a non-destructive,
      rapid analysis technique that requires only small sample volumes and has recently
      been used to evaluate the mineral content, mineral crystallinity, acid phosphate
      and carbonate contents, and collagen maturity in human and animal bones. Here, to
      establish a quality assessment method of allograft bones using Raman
      spectroscopy, the effect of several common sterilization and preservation
      procedures on rat femoral bones were investigated. We found that freeze-thawing
      had no detectable effects on the composition of bone minerals or matrix, although
      heat treatment and gamma irradiation resulted in altered Raman spectra. Our
      findings suggest Raman spectroscopy may facilitate the quality control of
      allograft bone after processing and sterilization procedures.

PMID- 21901325
TI  - Editorial policy on co-authorship of articles from low- and middle-income
      countries.

PMID- 21901323
TI  - Increased aortic stiffness can predict perioperative cardiovascular outcomes in
      patients undergoing noncardiac, nonvascular surgery.
AB  - BACKGROUND: Aortic stiffness is an early marker of arteriosclerosis and
      associated with cardiovascular mortality. However, the impact of aortic stiffness
      on perioperative cardiovascular outcomes in patients undergoing noncardiac
      surgery is unknown. METHODS: The study population was composed of 660 consecutive
      adults aged 18 years and over (mean age = 65.3 +/- 14 years) who underwent
      intermediate-risk (nonvascular), noncardiac surgery between January 2010 and
      February 2011. Nonemergency, non-day-case, open surgical procedures were
      enrolled. Aortic stiffness indices were calculated from the aortic diameters
      measured by echocardiography. Electrocardiography and cardiac biomarkers were
      evaluated 1 day before surgery, and on days 1, 3, and 7 after surgery. RESULTS:
      Eighty patients (12.1%) experienced perioperative cardiovascular events (PCE).
      Preoperative aortic distensibility (AD) (2 +/- 1.3 vs. 2.9 +/- 1.1 cm2/dyn/10(3),
      P < 0.001) and aortic strain (AS) (4.4 +/- 2.4 vs. 6.4 +/- 1.9, P < 0.001) of the
      patients with PCE were significantly lower than in patients without PCE.
      Univariate analysis showed a significant association between age, diabetes
      mellitus (DM), coronary artery disease, preoperative atrial fibrillation,
      American Society of Anesthesiologists (ASA) status, Revised Cardiac Risk Index,
      left ventricle ejection fraction (LVEF), AD, aortic strain, and in-hospital PCE.
      However, on multivariate logistic regression analysis, only AD (OR: 1.94, 95% CI:
      1.1-3.4; P = 0.02), AS (OR: 0.45, 95% CI: 0.3-0.6; P < 0.001), DM (OR: 2.28, 95%
      CI: 1.08-4.82; P = 0.03), and LVEF (OR: 0.96, 95% CI: 0.93-0.99; P = 0.03)
      remained as significant variables associated with PCE. CONCLUSION: Impaired
      elastic properties of the aorta are associated with increased PCE rates in
      patients undergoing noncardiac, nonvascular surgery.

PMID- 21901326
TI  - Distal pancreatectomy with celiac axis resection for carcinoma of the body and
      tail of the pancreas.
AB  - BACKGROUND: We retrospectively investigated our experiences with distal
      pancreatectomy with celiac axis resection (DP-CAR) for locally advanced
      pancreatic cancer and compared the operative outcome and long-term survival
      between DP-CAR and standard distal pancreatectomy (DP). Although several authors
      reported that DP-CAR increases resectability rates, the long-term results of this
      operation are not clear, and there are few reports presenting a comparison of the
      short- and long-term results between DP-CAR and DP. METHODS: From 1993 to 2010,
      43 patients with invasive ductal carcinoma of the body or tail of the pancreas
      underwent a macroscopically curative resection (R0/1). Sixteen patients underwent
      DP-CAR and 27 patients underwent DP. No DP-CAR patients underwent any
      preoperative coil embolization of the common hepatic artery (CHA) to stimulate
      the development of collateral pathways from the superior mesenteric artery. The
      perioperative and histopathologic parameters and survival data were analyzed to
      compare the two operations. RESULTS: There was no difference in mean operative
      time, mean blood loss, postoperative mortality, and morbidity between DP-CAR and
      DP. The rates of morbidity and in-hospital mortality of DP-CAR were 56 and 6%,
      respectively. In DP-CAR, 15 patients did not require reconstruction of the
      hepatic artery and no hepatic infarctions were clinically encountered after
      surgery. The estimated overall 1- and 3-year survival rates in patients who
      underwent DP-CAR were 42.6 and 25.6%, respectively, and their survival time was
      significantly less than that of patients who underwent DP (median survival time:
      9.7 vs. 30.9 months, P = 0.033). The R1 resection rates of these groups were 44%
      in DP-CAR and 22% in DP, respectively. CONCLUSION: DP-CAR is a safe and rational
      procedure for locally advanced pancreatic cancer without preoperative
      embolization of the CHA. Although the short-term results were equivalent to that
      for DP, DP-CAR did not improve the long-term survival because of the high rate of
      R1 resection at present.

PMID- 21901327
TI  - Conservative and surgical treatment of acute posttraumatic tracheobronchial
      injuries.
AB  - BACKGROUND: Acute posttraumatic tracheobronchial lesions are rare events
      associated with significant morbidity and mortality. They are caused by blunt and
      penetrating trauma, or they are iatrogenic, appearing after intubation or
      tracheotomy. Although surgery has traditionally been considered the treatment of
      choice for these injuries, recent reports show that conservative treatment can be
      effective in selected patients. The aim of this study was to evaluate the role of
      surgical and conservative management of these lesions, differentiated on the
      basis of clinical and endoscopic criteria. METHODS: From January 1993 to October
      2010, a total of 50 patients with acute posttraumatic tracheobronchial lesions
      were referred for treatment to our department. In all, 36 patients had iatrogenic
      injuries of the airway, and 14 had lesions resulting from blunt or penetrating
      trauma. RESULTS: Of the 30 patients who underwent surgery, the lesion was
      repaired with interrupted absorbable sutures in 29; the remaining patient, with
      an associated tracheoesophageal fistula, underwent single-stage tracheal
      resection and reconstruction and closure of the fistula. In all, 20 patients were
      treated conservatively: clinical observation in 5 patients, airway decompression
      with a mini-tracheotomy cannula in 4 spontaneously breathing patients, and
      tracheotomy with the cuff positioned distal to the lesion in 11 mechanically
      ventilated patients. One surgical and one conservatively-managed patient died
      after treatment (4% overall mortality). Complete recovery and healing were
      achieved in all the remaining patients. CONCLUSIONS: Surgery remains the
      treatment of choice for posttraumatic lesions of the airway. However,
      conservative treatment based on strict clinical and endoscopic criteria-stable
      vital signs; effective ventilation; no esophageal injuries, signs of sepsis, or
      evidence of major communication with the mediastinal space-enables favorable
      results to be achieved in selected patients.

PMID- 21901328
TI  - Accuracy of pedicle screw placement: a systematic review of prospective in vivo
      studies comparing free hand, fluoroscopy guidance and navigation techniques.
AB  - INTRODUCTION: With the advances and improvement of computer-assisted surgery
      devices, computer-guided pedicle screws insertion has been applied to the lumbar,
      thoracic and cervical spine. The purpose of the present study was to perform a
      systematic review of all available prospective evidence regarding pedicle screw
      insertion techniques in the thoracic and lumbar human spine. MATERIALS AND
      METHODS: We considered all prospective in vivo clinical studies in the English
      literature that assessed the results of different pedicle screw placement
      techniques (free-hand technique, fluoroscopy guided, computed tomography (CT)
      based navigation, fluoro-based navigation). MEDLINE, OVID, and Springer databases
      were used for the literature search covering the period from January 1950 until
      May 2010. RESULTS: 26 prospective clinical studies were eventually included in
      the analysis. These studies included in total 1,105 patients in which 6,617
      screws were inserted. In the studies using free-hand technique, the percentage of
      the screws fully contained in the pedicle ranged from 69 to 94%, with the aid of
      fluoroscopy from 28 to 85%, using CT navigation from 89 to 100% and using
      fluoroscopy-based navigation from 81 to 92%. The screws positioned with free-hand
      technique tended to perforate the cortex medially, whereas the screws placed with
      CT navigation guidance seemed to perforate more often laterally. CONCLUSIONS: In
      conclusion, navigation does indeed exhibit higher accuracy and increased safety
      in pedicle screw placement than free-hand technique and use of fluoroscopy.

PMID- 21901329
TI  - Comparison of Pentax-AWS Airwayscope video laryngoscope, Airtraq optic
      laryngoscope, and Macintosh laryngoscope during cardiopulmonary resuscitation
      under cervical stabilization: a manikin study.
AB  - PURPOSE: The 2010 American Heart Association or European Resuscitation Council
      guidelines for cardiopulmonary resuscitation emphasize that rescuers should
      minimize interruption of chest compressions, even for endotracheal intubation.
      Cervical stabilization should also be maintained during traumatic cardiac arrest.
      The utility of the Pentax-AWS Airwayscope (AWS) video laryngoscope and Airtraq
      (ATQ) optic laryngoscope for airway management has been reported under cervical
      stabilization. We first evaluated ATQ utility during chest compression with or
      without cervical stabilization and then compared the AWS, ATQ, and Macintosh
      laryngoscope (McL) during chest compressions under cervical stabilization in a
      manikin. METHODS: In the first trial, 19 novice doctors performed tracheal
      intubation with ATQ during chest compression with or without cervical
      stabilization. In the second trial, 21 novice doctors performed tracheal
      intubation on a manikin with cervical stabilization using AWS, ATQ, and McL with
      or without chest compression in a manikin. The rate of successful intubation,
      time to intubation, and subjective difficulty of use (visual analog scale) were
      recorded. RESULTS: In the first trial, intubation time during chest compression
      was significantly shortened under cervical stabilization compared to without
      cervical stabilization (P < 0.05). In the second trial, using McL, 3 participants
      failed to perform tracheal intubation without chest compression and 11 failed
      during chest compression (P < 0.05). Using ATQ, all intubations were successful
      without chest compression, but 5 failed during chest compression (P < 0.05).
      Intubation time was significantly prolonged by chest compression using McL or ATQ
      (P < 0.05). All participants successfully secured the airway with AWS regardless
      of chest compression, and chest compression did not prolong intubation time.
      Chest compression worsened the score on the visual analog scale of laryngoscopy
      in the McL trial (P < 0.05), but not in ATQ or AWS trials. Difficulty of tube
      passage through the glottis increased with chest compression with the McL and ATQ
      (P < 0.05) but not with AWS. CONCLUSION: The AWS was superior to McL and ATQ for
      endotracheal intubation during simulated cervical stabilization and chest
      compression.

PMID- 21901330
TI  - Dexmedetomidine can stabilize hemodynamics and spare anesthetics before
      cardiopulmonary bypass.
AB  - PURPOSE: We previously confirmed the effectiveness of dexmedetomidine (DEX) for
      stabilizing hemodynamics as well as sparing anesthetics during anesthetic
      induction in patients undergoing cardiac surgery (Kunisawa et al. in J Clin
      Anesth 21:194-199, 1). In this study, we investigated whether these effects of
      DEX continue until the start of cardiopulmonary bypass (CPB). METHODS: Twenty-two
      patients with mild to moderate cardiovascular disease were randomized into two
      groups [DF2 group: DEX dose of 0.7 MUg/kg/h after initial dose and effect-site
      concentration (ESC) of fentanyl of 2 ng/ml; PF4 group: saline and ESC of fentanyl
      of 4 ng/ml]. Propofol was administered for anesthetic induction and maintenance.
      Hemodynamics, cardiovascular drugs, ESC of propofol, and cardiovascular responses
      to skin incision (SI) and sternotomy (St) were measured or calculated. RESULTS:
      Blood pressure (BP) at the pre-/post-SI periods was higher in the DEX group (137
      +/- 17/140 +/- 16 mmHg) than in the placebo group (85 +/- 9/109 +/- 24 mmHg).
      Percent increases in cardiovascular response to SI or St were lower in the DEX
      group than in the placebo group (for example, 1.9 +/- 2.2 vs. 27.4 +/- 19.9% in
      systolic BP due to SI). ESCs of propofol at SI and St in the DEX group were lower
      than those in the placebo group. CONCLUSIONS: DEX combined with 2 ng/ml fentanyl
      before CPB can suppress the decrease in blood pressure at the pre- and post-SI
      periods, can blunt the cardiovascular responses to SI and St, and can spare the
      required ESC of propofol despite fentanyl concentration, which was half of that
      in the placebo group.

PMID- 21901331
TI  - L-type Cav1.2 calcium channel is involved in 6-hydroxydopamine-induced
      neurotoxicity in rats.
AB  - Evidence suggested that L-type calcium channels may play a key role in the
      pathogenesis of dopaminergic neuron degeneration. In the present study, effects
      of L-type Cav1.2 calcium channel on 6-hydroxydopamine (6-OHDA)-induced
      neurotoxicity were investigated. By the semi-quantitative reverse transcription
      polymerase chain reaction (RT-PCR) studies, we showed that the expression of L
      type Cav1.2 calcium channel alpha1 subunit mRNA increased in the substantia nigra
      (SN) of 6-OHDA-lesioned rats. Treatment with nifedipine could improve the
      apomorphine-induced rotation behavior in 6-OHDA-lesioned rats. Using high
      performance liquid chromatography electrochemical detection, we also observed
      that nifedipine partly restored 6-OHDA-induced dopamine depletion in the striatum
      of rats. These results suggest that the L-type Cav1.2 calcium channel is
      associated with the development and progression of dopaminergic neuron
      degeneration.

PMID- 21901333
TI  - Exploring the quality of life (QOL) in the Indian software industry: a public
      health viewpoint.
AB  - OBJECTIVES: Our objectives were to describe the QOL and its determinants among
      software professionals of Kolkata, and to compare the same according to
      information technology (IT) and IT-enabled services (ITeS) sub-sectors. METHODS:
      An institution-based cross-sectional study was conducted among software
      professionals of Kolkata applying a two-stage stratified random sampling
      technique. The WHO QOL BREF questionnaire was administered along with a list of
      pertinent variables. RESULTS: Overall, the analysis for 338 software
      professionals (177 IT and 161 ITeS) clearly demonstrated significant differences
      between mean scores of these two sectors for each of the six outcome domains of
      WHO QOL BREF. Multilevel multivariate analysis outlined 13 significant predictors
      of QOL-four positive (age, regular fitness regimes, foreign placements and
      changing companies frequently) and the rest of the nine, negative (multiple sex
      partners, multiple addictions, extended working hours, night-shift duties,
      income, expenditure, carrying office work home, current illness and ITeS company
      type). CONCLUSIONS: Our study helps in obtaining a clear understanding of the
      multifaceted risk factors prevailing in this sector, the majority of which can be
      effectively addressed by specific health promotional interventions. A dedicated
      health policy is mandated at both government and company levels.

PMID- 21901332
TI  - The prevalence and management of cardiovascular risk factors in immigrant groups
      in Switzerland.
AB  - OBJECTIVES: To compare the prevalence and management of cardiovascular risk
      factors (CVRFs) between immigrant groups and Swiss nationals. METHODS: The Swiss
      Health Surveys (SHS, N = 49,245) and CoLaus study (N = 6,710) were used.
      Immigrant groups from France, Germany, Italy, Portugal, Spain, former Yugoslavia,
      other European and other countries were defined. RESULTS: Immigrants from Italy,
      France, Portugal, Spain and former Yugoslavia presented a higher prevalence of
      smoking than Swiss nationals. Immigrants reported less hypertension than Swiss
      nationals, but the differences were reduced when blood pressure measurements were
      used. The prevalence of dyslipidaemia was similar between immigrants and Swiss
      nationals in the SHS. When eligibility for statin treatment was assessed,
      immigrants from Italy were more frequently eligible than Swiss nationals.
      Immigrants from former Yugoslavia presented a lower prevalence of diabetes in the
      SHS, but a higher prevalence in the CoLaus study. Most differences between
      immigrant groups and Swiss nationals disappeared after adjusting for age, leisure
      time physical activity, being overweight/obesity and education. CONCLUSIONS: Most
      CVRFs are unevenly distributed among immigrant groups in Switzerland, but these
      differences are due to disparities in age, leisure-time physical activity, being
      overweight/obesity and education.

PMID- 21901334
TI  - Lack of research-based standards for accessible housing: problematization and
      exemplification of consequences.
AB  - OBJECTIVE: To increase the understanding of how definitions of standards for
      housing design influence the proportion of dwellings not meeting the standards
      and the proportion of individuals defined as having accessibility problems.
      METHODS: The sample included old people and their dwellings in three European
      countries (N = 1,150). Frequencies and percentages were reported and empirical
      distribution functions were used. RESULTS: Depending on the functional profile
      and standards in question, the magnitude of influence of the standards differs in
      extent, e.g., the existing standard for door openings at the entrance (defined
      >=75 cm) implied that the proportion of dwellings not meeting it was 11.3%
      compared to 64.4%, if the standard was set to >=83 cm. The proportion of
      individuals defined as having accessibility problems for profiles not using
      mobility devices was 4-5, 57% for profiles using them and 1-3% for the total
      sample if the standard was set to 90 cm. CONCLUSION: Research-based standard
      definitions for housing design are necessary to ensure that they actually lead to
      enhanced accessibility, which is a prerequisite for the independence and health
      of persons with functional limitations.

PMID- 21901335
TI  - Dose dependence specific and non-specific immune responses of Indian major carp
      (L. rohita Ham) to intraperitoneal injection of formalin killed Aeromonas
      hydrophila whole cell vaccine.
AB  - Specific and non-specific immune response to different doses of formalin killed
      whole cell vaccine of Aeromonas hydrophila to Indian major carp (Labeo rohita)
      was evaluated in laboratory condition. Three different doses (10(5) CFU/ml, 10(7)
      CFU/ml, 10(10) CFU/ml) were administered (0.2 ml/fish) intraperitoneally for 1
      month. Among the three doses, 10(10) CFU/ml elicited the highest antibody and
      protective response followed by the doses 10(7) CFU/ml and 10(5) CFU/ml. Upon
      challenge with the virulent strain of A. hydrophila, the relative percentage of
      survival was recorded up to 80% at highest dose of 10(10) CFU/ml. The non
      specific responses, similar to the specific immune responses were also maximum at
      highest dose of 10(10) CFU/ml. Similar to the specific immune responses, the non
      specific responses were maximum at highest dose of 10(10) CFU/ml. Therefore, dose
      containing 10(10) CFU/ml of formalin killed cells was found to be the most
      effective dose for vaccination which increased the immunity in Indian major carp
      (Labeo rohita) to a larger extent.

PMID- 21901336
TI  - Use of 2-Octyl-Cyanoacrylate in surgical closing of Postparotidectomy salivary
      fistulas.
AB  - A salivary fistula is one of possible postoperative complications in the surgery
      of parotid gland tumors. We present three cases of postparotidectomy salivary
      fistulas, successfully treated by surgical access using 2-octyl-cyanoacrylate
      while closing the skin layer. The previous treatment of these cases by other
      therapeutic options did not give satisfactory results. In a 5-year follow-up
      period there were no signs of fistulas relapses. The surgical access with use of
      2-octyl cyanoacrylate can be one of therapeutic options for the closing of
      postparotidectomy salivary fistulas, especially in cases where other therapeutic
      accesses are not successful.

PMID- 21901337
TI  - Medical and surgical treatment in divers with chronic rhinosinusitis and
      paranasal sinus barotrauma.
AB  - Aim of the study is to evaluate the effects of medical and surgical treatment in
      divers with paranasal sinus barotrauma (PSB) secondary to chronic rhinosinusitis
      (CRS). In this retrospective, cross-sectional, descriptive study 40 adult divers
      with CRS were included. Treatment of divers implied a 5-day course of a systemic
      steroid and a 6-week course of saline nasal irrigations and topical nasal steroid
      with mometasone in maximal dosage. If symptoms persisted, functional endoscopic
      sinus surgery (FESS) was performed. Questionnaires included the Sinonasal Outcome
      Test-20 German Adapted Version (SNOT-20 GAV), dive-related questions (DRQ) and
      general questions. Questionnaires were completed retrospectively by recalling the
      symptoms before and after therapy. Forty of 82 divers completed the
      questionnaires. Mean follow-up was 42 months (range 13-95 months). There was a
      statistically significant improvement of the Total score (TS) and of every
      subscore, except the General Quality of Life score, in the SNOT-20 GAV as well as
      of the TS in the DRQ. Before treatment, divers who required surgery reported
      significantly more symptoms than divers who were treated conservatively. Post
      treatment there were no significant differences between the medical and surgical
      group. Overall, 35 divers could resume diving after therapy even though PSB still
      occurred but without complications. Divers with sinus problems can successfully
      be managed medically and if conservative treatment fails, FESS shows a
      statistically significant improvement of symptoms and no serious long-term
      hazards for diving.

PMID- 21901339
TI  - New insights on pathophysiology, clinical manifestations, diagnosis, and
      treatment of sickle cell nephropathy.
AB  - Sickle cell nephropathy is one of the main chronic complications of sickle cell
      disease (SCD), the most common of the hematological hereditary disorders. Several
      studies have been performed since the first description of SCD 100 years ago to
      investigate the mechanisms of kidney involvement in this disease. It has been
      demonstrated that both glomerular and tubular compartments can be damaged as a
      direct consequence of SCD, including renal function loss, concentration and
      acidification deficits, and glomerulopathies. This article highlights the aspects
      of sickle cell nephropathy pathophysiology and clinical manifestations and
      describes the most recent advances in the diagnosis and treatment of this
      disorder.

PMID- 21901340
TI  - Gene mutations in the Ras pathway and the prognostic implication in Korean
      patients with juvenile myelomonocytic leukemia.
AB  - Juvenile myelomonocytic leukemia (JMML) is a rare hematologic malignancy in
      children. Hyperactivation of the Ras pathway from gene mutations is known to be
      the key culprit in the development of JMML. In this study, we investigated Ras
      pathway mutations and prognostic implication in Korean patients with JMML. A
      total of 22 Korean patients with JMML were recruited from two institutions (19
      boys and three girls; median age, 17 months; range, 1-74 months). Hematologic and
      cytogenetic findings were reviewed. Mutation analyses involved PTPN11, KRAS,
      NRAS, and CBL genes by direct sequencing analyses (selected exons except in CBL).
      Survival analysis was performed by the Kaplan-Meier method. Cytogenetic and/or
      gene mutations were detected in 18 patients out of 22 (82%). Four patients (18%)
      had chromosomal abnormalities, with monosomy 7 being the most common. Seventeen
      (77%) had gene mutations. PTPN11 mutations were detected in 13 patients (59%).
      The patient heterozygous for c.854T>C had Noonan syndrome. NRAS and KRAS
      mutations were detected in two patients (9%) and one patient (5%), respectively.
      A homozygous CBL mutation was detected in one patient (5%; c.1228-2A>G). All
      mutations detected were previously reported mutations. Survival analyses
      suggested an unfavorable prognostic implication of PTPN11 mutation, albeit
      without a statistical significance. Collectively, the results from molecular
      genetics study and survival analyses suggested a relatively higher frequency and
      unfavorable prognostic implication of PTPN11 mutations in Korean patients with
      JMML.

PMID- 21901341
TI  - Successful treatment of IgM-monoclonal gammopathy of undetermined significance
      associated with cryoglobulinemia and cold agglutinin disease with
      immunochemotherapy with rituximab, fludarabine, and cyclophosphamide.

PMID- 21901342
TI  - Long-term results of thalidomide and dexamethasone (thal-dex) as therapy of first
      relapse in multiple myeloma.
AB  - Thal-dex (TD) is an effective therapy for advanced MM. We evaluated TD as salvage
      treatment of MM patients at first relapse. Thal was given at a daily dose of 100
      or 200 mg until progression. Dex was administered 160 mg/month. One hundred
      patients were enrolled. First line therapy included ASCT (72%) and conventional
      CHT (28%). Fifty-nine percent received a fixed thal dose of 100 mg/day. The most
      frequent adverse events were constipation (42%), peripheral neuropathy (58%, 5%
      grade 3), bradycardia (20%), skin rash (11%), and VTE (7%). Discontinuation of
      thal due to adverse events was recorded in eight patients. On ITT, 46% of
      patients achieved at least a PR. Median DOR was 28 months, median time to next
      therapy was 15.5 months. Median OS, TTP, and PFS were 43, 22, and 21 months,
      respectively. TTP and PFS were significantly longer for patients with at least PR
      to TD. TD was an effective salvage treatment for MM patients at first relapse, as
      demonstrated by durable disease control and prolonged OS. TD was well tolerated,
      as reflected by the long stay on treatment without disease progression (median 25
      months) and a low discontinuation rate due to toxicity (8%).

PMID- 21901343
TI  - Extracellular secretion of anticoagulant peptide hirudin in Lactococcus lactis
      using SP310mut2 signal peptide.
AB  - Hirudin can be used as an oral anticoagulant and antithrombotic agent. The
      hirudin variant III gene, derived from the medicinal leech, Hirudo medicinalis,
      was fused to SP310mut2 signal sequence and expressed by a nisin-controlled gene
      expression system in Lactococcus lactis which was then grown in a 7 l fermenter.
      After induction with 8 ng nisin ml(-1), the product was secreted into the culture
      medium and accumulated up to ~2.7 mg l(-1). MALDI-TOF/MS and anticoagulant
      activity analyses on the purified product confirmed its authenticity. This is the
      first demonstration that hirudin can be extracellularly secreted and correctly
      processed in L. lactis.

PMID- 21901344
TI  - CYP2B6 genotype is a strong predictor of systemic exposure to efavirenz in HIV
      infected Zimbabweans.
AB  - OBJECTIVE: Efavirenz, an antiretroviral medicine, is extensively metabolized by
      cytochrome P450 2B6 (CYP2B6), UDP-glucuronosyltransferase 2B7 (UGT2B7), and
      CYP2A6. In this study, we investigated the association of single nucleotide
      polymorphisms (SNPs) in these genes with plasma efavirenz levels in Zimbabwean
      human immunodeficiency virus (HIV)-positive patients treated with efavirenz.
      METHODS: The exon regions of the CYP2B6, CYP2A6, and UGT2B7 genes were re
      sequenced in 49 HIV-infected Zimbabwean patients treated with a combination
      therapy including efavirenz. Associations of SNPs in these three genes with
      efavirenz plasma concentrations 11-16 h after the administration of treatment
      were evaluated. RESULTS: Eight patients carrying CYP2B6*6/*18 showed the highest
      plasma efavirenz levels, with a fourfold higher concentration than patients who
      carried CYP2B6*1/*1. Patients with CYP2B6*6/*6 also showed higher efavirenz
      plasma concentrations than those with CYP2B6*1/*1. Among the 17 and 12 SNPs
      identified in CYP2A6 and UGT2B7, respectively, no SNP showed a significant
      association with the plasma efavirenz concentration. CONCLUSION: Although based
      on only a limited number of subjects, our results suggest that the CYP2B6*6 and
      CYP2B6*18 alleles should affect hepatic metabolic activity and elevate the
      systemic circulation level of efavirenz, which may lead to toxicity in Zimbabwean
      HIV patients.

PMID- 21901345
TI  - Natriuretic peptides in therapy for decompensated heart failure.
AB  - Congestive heart failure (CHF) is the most frequent cause of hospitalization for
      patients >65 years of age and continues to be a major public health burden among
      the ageing population. Unlike therapy for chronic CHF, there has been only modest
      progress in medical treatment for acutely decompensated CHF over the past several
      decades. Moreover, current treatment-consisting generally of diuretic, inotropic,
      and vasodilatory agents-is associated with many limitations in clinical practice.
      Natriuretic peptides provide a promising mechanism of action in the
      pathophysiologic background for CHF treatment based on their vasodilatory and
      diuretic properties and effective inhibition of the renin-angiotensin-aldosterone
      system, which is activated early in the course of CHF. Nesiritide (Natrecor(r) or
      Noratak(r)) is a recombinant natriuretic peptide that has the same 32 amino-acid
      sequence as human B-type natriuretic peptide. Nesiritide has been shown to
      improve dyspnea and hemodynamic parameters in patients with decompensated heart
      failure. Ularitide is a synthetic form of urodilatin, a natriuretic peptide
      hormone secreted by the kidney. Recent clinical studies suggest that ularitide
      may play a role in managing decompensated heart failure. This review provides an
      update on natriuretic peptides and their therapeutic potential in advanced CHF.

PMID- 21901348
TI  - How to diagnose double crush syndrome?

PMID- 21901347
TI  - Bone marrow lesions: a universal bone response to injury?
AB  - The ever increasing use of magnetic resonance imaging in clinical practice has
      led to the recognition of a new entity, bone marrow lesions (BMLs). These lesions
      are characterized by excessive water signals in the marrow space and have emerged
      as a central component of many different diseases affecting the musculoskeletal
      system. BMLs have in particular been associated with a wide variety of
      inflammatory and non-inflammatory rheumatologic conditions and are not only
      considered significant sources of pain, but also linked to the worsening of
      patient prognosis in many disease states. In this review, we summarize the
      current knowledge on BMLs with an emphasis on the clinical and histological
      features of this entity in inflammatory and non-inflammatory disease and provide
      a unifying hypothesis based on the appearance with various imaging technologies.
      We also try to pair this hypothesis with the apparent beneficial effects of
      various treatment regimens, mainly within the group of bone antiresorptive drugs
      (calcitonin, bisphosphonates) on symptoms associated with BMLs.

PMID- 21901349
TI  - Churg-Strauss syndrome presented as paraneoplastic syndrome with thymic
      neuroendocrine carcinoma: a case report.
AB  - Churg-Strauss syndrome (CSS) is rarely presented as paraneoplastic syndrome. We
      reported here a 47-year-old man with refractory asthma for 3 years, and his CT
      scan showed an anterior mediastinal mass, pulmonary reticular opacities and
      bilateral maxillary sinusitis. He also presented with elevated peripheral blood
      eosinophils (EOS). Thoracoscopic resection of the mediastinal mass and a lung
      biopsy were performed, and thymic neuroendocrine carcinoma (TNC) and pulmonary
      eosinophilic vasculitis were pathologically diagnosed. The laboratory and
      clinical findings fulfilled the criteria of the diagnosis of CSS (Masi et al. in
      Arthritis Rheum 33(8):1094-1100, 1990). Asthma was improved, and elevated EOS was
      recovered to normal range after surgery and four courses of chemotherapy. This
      was the first report of CSS manifested as a paraneoplastic syndrome of TNC.

PMID- 21901351
TI  - Magnetic resonance imaging of rheumatoid meningitis: a case report and literature
      review.
AB  - Rheumatoid meningitis is a rare and serious complication of rheumatoid arthritis
      (RA) with high mortality rate. Clinical importance of the disease is high because
      diagnosis is difficult, and the disease is treatable if diagnosed successfully.
      We present the clinical and cranial magnetic resonance imaging findings of 62
      year-old female patient with RA who has been followed up for 4 years.

PMID- 21901350
TI  - Scleroderma pattern of nailfold capillary changes as predictive value for the
      development of a connective tissue disease: a follow-up study of 3,029 patients
      with primary Raynaud's phenomenon.
AB  - To assess the prognostic value of scleroderma pattern of nailfold capillary
      changes for the development of connective tissue diseases (CTD) in subjects with
      primary Raynaud's phenomenon (RP). The study included 3,029 consecutive patients
      with primary RP who had been followed at 6-month intervals during the mean of 4.8
      years. The pathological features of nailfold capillaroscopy were recorded in all
      patients who had neither clinical nor serological signs of a CTD. In patients who
      developed CTD, capillary changes obtained 6 months prior to diagnosis were
      analyzed. A possible relationship between capillary changes and the presence of
      associated CTD was assessed. At the end of follow-up, 1,660 (54,8%) patients have
      still the primary RP, 246 (8,1%) had suspected secondary RP, and 1,123 (37,1%)
      patients developed CTD (363 undifferentiated CTD, 263 systemic sclerosis, 143
      systemic lupus erythematosus, 106 rheumatoid arthritis, 102 Sjogren's syndrome,
      61 overlap syndrome, 30 vasculitides, 24 mixed CTD, 19 polymyositis, 7
      dermatomyositis, and 5 primary antiphospholipid syndrome). Scleroderma pattern
      were significantly associated with the development of systemic sclerosis [P =
      .00001, sensitivity 94%, specificity 92%, positive predictive value 52%, negative
      predictive value 99%, and odds ratio 163 (95% CI, 97,9-271,5)], as well as
      dermatomyositis (P = .0004), overlap syndrome with signs of systemic sclerosis (P
      = .0001), and mixed connective tissue disease (P = .007). Capillary microscopy is
      effective method for differentiation between primary and secondary RP and useful
      tool for the prediction of scleroderma spectrum disorders in RP patients.

PMID- 21901352
TI  - Association of fibromyalgia characteristics in patients with non-metastatic
      breast cancer and the protective role of resilience.
AB  - Cancer patients often complain about weakness, fatigue, and pain. The aim of this
      study was to assess the features of the fibromyalgia syndrome (FMS)
      characteristics in patients with non-metastatic breast cancer. The study group
      included 40 women whose age ranged from 40 to 70 years with Stages 0-3 breast
      cancer. The control group included 40 healthy women matched by age. A diagnosis
      of FMS was established based on medical history, physical examination, and the
      Fibromyalgia Impact Questionnaire (FIQ). Pain measures and functional factors
      were evaluated by the Brief Pain Inventory and the Sheehan Questionnaire.
      Resilience was assessed by Antanovsky's Sense of Coherence Questionnaire.
      Psychiatric disturbances were tested by the MINI Questionnaire and Hamilton
      questionnaires for depression and anxiety. The prevalence of chronic pain was
      higher in the study group. Statistically significant differences were also found
      between the group regarding pain, fatigue, and functional measures. The
      prevalence of depressive or anxious mood, measured by the Hamilton
      questionnaires, was strongly related to FMS characteristics reflected by FIQ
      scores (r = 0.79 between FIQ and the Hamilton Depression Index and r = 0.75
      between FIQ and the Hamilton Anxiety Scale). The sense of coherence measure for
      these patients demonstrated an inverse correlation with pain, fatigue, and
      functional capability. Women with breast cancer tend to develop chronic
      widespread pain syndromes more often than do healthy women.

PMID- 21901353
TI  - SUMO4 C438T polymorphism is associated with papulopustular skin lesion in Korean
      patients with Behcet's disease.
AB  - Small ubiquitin-like modifier 4 (SUMO4) is involved in a range of autoimmune
      diseases and is known to downregulate the transcription activity of nuclear
      factor kappa B (NF-kappaB). Our objective was to investigate the association of a
      certain polymorphism (C438T) of the SUMO4 gene with Behcet's disease (BD) in
      terms of its incidence and clinical features in Korean patients. We consecutively
      enrolled 83 patients with BD and 120 healthy controls. Genomic DNA was extracted
      from whole-blood samples. We identified a single nucleotide change (C438T) in the
      SUMO4 gene using an amplification refractory mutation system (ARMS) technique. To
      validate the ARMS technique, we compared its results to the results of direct
      sequencing in 20 subjects. HLA-B51 status was determined by polymerase chain
      reaction sequence-specific primers. The presence of papulopustular lesions (P =
      0.006) and vascular involvement (P = 0.045) was significantly different between
      C438T genotypes in HLA-B51-positive patients with BD. There were no differences
      in allelic or genotypic frequencies of the SUMO4 C438T polymorphism between
      patients with BD and controls (P = 0.567 and P = 0.818, respectively). The
      difference in papulopustular skin lesions between CC and CT + TT genotypes in HLA
      B51-positive patients with BD was also statistically significant (P = 0.002, OR =
      23.40, 95% CI: 2.33-235.54). The C438T polymorphism in the SUMO4 gene is
      associated with significantly increased risk of papulopustular skin lesions in
      HLA-B51-positive patients.

PMID- 21901354
TI  - Progress in pediatric rheumatology: apprehend the opportunities of the future
      without forgetting the lessons from the past.

PMID- 21901356
TI  - Reactivation of hepatitis B virus in a hepatitis B surface antigen-negative
      patient with rheumatoid arthritis treated with methotrexate.
AB  - Immunosuppressive therapy can induce viral reactivation in patients with chronic
      hepatitis B virus (HBV) infection and, more rarely, in patients with resolved HBV
      infection. We report the case of a 57-year-old Japanese woman with rheumatoid
      arthritis (RA) who developed de-novo hepatitis B virus-related hepatitis after
      methotrexate (MTX) therapy. Entecavir and oral prednisolone following steroid
      pulse therapy were administered and her liver function recovered. MTX is widely
      used for RA for its efficiency and safety. But some cases of HBV reactivation
      caused by MTX, including de-novo hepatitis, have been reported. Considering these
      conditions, more attention should be paid when using MTX in patients with RA. And
      more studies are needed to determine who needs screening of HBV, monitoring of
      HBV-DNA, and prophylaxis with chemotherapy or immunosuppressive therapy.

PMID- 21901355
TI  - The frequency of MEFV gene mutations in Behcet's disease and their relation with
      clinical findings.
AB  - Investigation of the relation between MEFV gene mutations and clinical findings
      of Behcet's disease. Genetic features of 100 patients with Behcet's disease (BD)
      and 100 healthy controls were analyzed. None of the individuals had a family
      history of FMF in the patient and control group, and none of the individuals in
      the control group had a family history of BD. MEFV gene analysis was performed in
      all the patients with BD and healthy controls; twelve different regions were
      scanned. In the BD group, mutations were detected in more than one region in 27
      patients (27%). Twenty-five patients had heterozygous and two patients had
      compound heterozygous mutations (M680I-V726A and M694 V-A744S). The most frequent
      mutation was M694 V with an allelic frequency of 5%. The allelic frequencies of
      E148Q, M680I (G/C), and V726A were 3, 2, and 2%, respectively. The allelic
      frequencies of P369S, A744S, and K695R were 1, 1, and 0.5%. MEFV gene analysis
      revealed mutations in 27 (27%) of the individuals in the control group; the
      allelic frequency was 14%. The most frequent mutation was E148Q that was detected
      in 16 individuals. One individual was compound heterozygote (E148Q-M694 V). The
      allelic frequencies of E148Q, M694 V, V726A, and M680I were 8, 3, 1.5, and 0.5%,
      respectively. The allelic frequencies of K695R and P369S were 0.5 and 0.5%,
      respectively. The allelic frequency was similar in the two groups. There was not
      a significant relation between the mutations in the BD group and clinical
      findings.

PMID- 21901357
TI  - Structural damages disturb functional improvement in patients with rheumatoid
      arthritis treated with etanercept.
AB  - Tumor necrosis factor (TNF) inhibitors have produced improvements in clinical,
      radiographic, and functional outcomes in rheumatoid arthritis (RA) patients.
      However, it remains unclear whether factors affecting physical functions remain
      following TNF therapy. The objective of our study was to assess factors affecting
      improvement of physical functions and to shed light on relations to disease
      activity and structural changes in patients with RA treated with etanercept. The
      study enrolled 208 patients, all of whose composite measures regarding clinical,
      radiographic, and functional estimation both at 0 and 52 weeks after etanercept
      therapy were completed. Mean disease duration of 208 patients was 9.6 years, mean
      Disease Activity Score for 28 joints (DAS28) was 5.4, and mean van der Heijde
      modified total Sharp score (mTSS) was 94.6. Mean Health Assessment Questionnaire
      Disability Index (HAQ-DI) improved from 1.4 at 0 weeks to 1.0 at 52 weeks after
      etanercept therapy, a 31% reduction, which was much less than changes in DAS28
      and mTSS. By multivariate analysis, HAQ-DI and mTSS at baseline were
      significantly correlated HAQ remission. Median HAQ-DI improved in 100 versus 20%
      of the HAQ-DI <= 0.6 versus >= 2.0 groups, respectively. The mTSS cutoff point at
      baseline to obtain HAQ remission was 55.5. During etanercept treatment in the
      mTSS <55.5 versus >55.5 groups, median HAQ-DI improved in 70 versus 39%;
      remission was achieved in 59 versus 33%; and there was no improvement in 14
      versus 30%, respectively. HAQ-DI improvement was significantly correlated with
      that of DAS28 but not of mTSS. In conclusion, higher HAQ and mTSS at baseline
      inhibits HAQ-DI improvement within 1 year of etanercept treatment, and the cutoff
      point necessary for mTSS to improve physical functions in patients with RA was
      55.5.

PMID- 21901358
TI  - Method to predict the chance of developing a male profile out of mixtures of male
      and female DNA.
AB  - In forensic examination it is a standard to take vaginal swabs from victims of
      sexual assault for further molecular genetic analysis. Laboratories then are
      usually confronted with mixtures of lots of female and only a small amount of
      male DNA. Nowadays it is possible to work with specific Y chromosomal markers
      after DNA extraction by differential lysis. The determined ratio of autosomal DNA
      and Y chromosomal DNA can be used to identify the possibility of generating a
      male profile in these samples.

PMID- 21901359
TI  - A web-based e-learning programme for training external post-mortem examination in
      curricular medical education.
AB  - In Germany, the external post-mortem examination is considered a medical duty and
      may be performed by any licensed physician. Concerning legal medicine as a
      curricular subject in teaching medical students, the external post-mortem
      examination is regarded a core area. At the University of Muenster, 15 virtual
      cases of death have been developed by using the web-based Inmedea Simulator. The
      programme allows performing all relevant steps in executing a complete external
      post-mortem examination. A particular importance was attached to the aspect of
      training users in approaching the subject in a systematic way to interpret
      significant forensic findings correctly and to comprehend their medico-legal
      implications. The programme was used for the first time in the academic term of
      2010/2011. The overall reception of the programme by the medical students
      resulted to be positive in a first evaluation.

PMID- 21901360
TI  - Species traits and environmental conditions govern the relationship between
      biodiversity effects across trophic levels.
AB  - Changing environments can have divergent effects on biodiversity-ecosystem
      function relationships at alternating trophic levels. Freshwater mussels
      fertilize stream foodwebs through nutrient excretion, and mussel species-specific
      excretion rates depend on environmental conditions. We asked how differences in
      mussel diversity in varying environments influence the dynamics between primary
      producers and consumers. We conducted field experiments manipulating mussel
      richness under summer (low flow, high temperature) and fall (moderate flow and
      temperature) conditions, measured nutrient limitation, algal biomass and grazing
      chironomid abundance, and analyzed the data with non-transgressive overyielding
      and tripartite biodiversity partitioning analyses. Algal biomass and chironomid
      abundance were best explained by trait-independent complementarity among mussel
      species, but the relationship between biodiversity effects across trophic levels
      (algae and grazers) depended on seasonal differences in mussel species' trait
      expression (nutrient excretion and activity level). Both species identity and
      overall diversity effects were related to the magnitude of nutrient limitation.
      Our results demonstrate that biodiversity of a resource-provisioning (nutrients
      and habitat) group of species influences foodweb dynamics and that understanding
      species traits and environmental context are important for interpreting
      biodiversity experiments.

PMID- 21901361
TI  - The model-data fusion pitfall: assuming certainty in an uncertain world.
AB  - Model-data fusion is a powerful framework by which to combine models with various
      data streams (including observations at different spatial or temporal scales),
      and account for associated uncertainties. The approach can be used to constrain
      estimates of model states, rate constants, and driver sensitivities. The number
      of applications of model-data fusion in environmental biology and ecology has
      been rising steadily, offering insights into both model and data strengths and
      limitations. For reliable model-data fusion-based results, however, the approach
      taken must fully account for both model and data uncertainties in a statistically
      rigorous and transparent manner. Here we review and outline the cornerstones of a
      rigorous model-data fusion approach, highlighting the importance of properly
      accounting for uncertainty. We conclude by suggesting a code of best practices,
      which should serve to guide future efforts.

PMID- 21901362
TI  - Resilience in infertile couples acts as a protective factor against infertility
      specific distress and impaired quality of life.
AB  - OBJECTIVE: Our hypothesis was that resilience (=psychosocial stress-resistance)
      reduces infertility-specific distress and maintains quality of life of infertile
      couples. METHODS: Questionnaire data of WHO Quality of Life assessment (WHOQOL;
      domains: 'physical', 'psychological', 'social relationships' and 'environment'),
      Fertility Problem Inventory (FPI; scales: 'social concern', 'sexual concern',
      'relationship concern', 'rejection of childfree lifestyle' and 'need for
      parenthood'), Resilience Scale (RS), as well as sociographic and medical data
      were available for 199 infertile couples. RESULTS: Age, medical diagnosis and
      'intensity of desire for a child' had no influence on quality of life. High
      scores on 'suffering from childlessness' went along with less satisfaction on
      'physical' and 'psychological' domains for the women only. For both partners,
      high scores on 'suffering from childlessness' went along with higher scores on
      all FPI scales. High resilience was associated with high scores on all WHOQOL
      domains for both partners, also with low scores on all FPI scales except for
      'need for parenthood' for the women and with a low score only on 'relationship
      concern' for the men. CONCLUSIONS: For infertile couples, resilience can be
      considered as an unspecific protective factor against infertility-specific
      distress and impaired quality of life. When offering counselling to involuntarily
      childless couples, awareness should be raised for resilience as a couple's
      resource and a "generic" factor of coping.

PMID- 21901363
TI  - Brain-derived neurotrophic factor from follicular fluid is positively associated
      with rate of mature ooocytes collected and cleavage rate in intracytoplasmic
      sperm injection patients.
AB  - PURPOSE: The aim of the study was to evaluate the correlation between BDNF and
      oocyte maturation and to verify whether BDNF could predict in vitro fertilization
      (IVF) outcome. METHODS: The follicle fluid (FF) for BDNF, E(2) and P assay were
      obtained from 59 patients undergoing intracytoplasmic sperm injection (ICSI). The
      women were divided into two groups by pregnancy outcome and their clinical and
      lab data were compared. And the correlation of BDNF with E(2), P, age, and IVF
      data were analyzed. RESULTS: Positive correlation was observed between BDNF and
      E(2) concentration in FF. BDNF was positively correlated with the rate of mature
      oocytes collected and cleavage rate. CONCLUSIONS: The BDNF in FF could not
      predict IVF outcome, but BDNF in FF might play an important role in the
      maturation of oocyte and development of oocyte into preimplantation embryo.

PMID- 21901364
TI  - Amelioration of neurodegenerative changes in cellular and rat models of diabetes
      related Alzheimer's disease by exendin-4.
AB  - Growing evidence suggests that type 2 diabetes mellitus (DM) is associated with
      age-dependent Alzheimer's disease (AD), the latter of which has even been
      considered as type 3 diabetes. Several physiopathological features including
      hyperglycemia, oxidative stress, and dysfunctional insulin signaling relate DM to
      AD. In this study, high glucose-, oxidative stress-induced neuronal injury and
      intracerebroventricular-streptozotocin (ICV-STZ) animals as the possible models
      for diabetes-related AD were employed to investigate the effects of exendin-4 (Ex
      4), a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, on diabetes
      associated Alzheimer-like changes as well as the molecular mechanisms involved.
      Our study demonstrated that GLP-1/Ex-4 could exert a protective effect against
      reduced viability of PC12 cells caused by high glucose and that this protective
      effect was mediated via the PI3-kinase pathway. In addition, GLP-1/Ex-4
      ameliorated oxidative stress-induced injury in PC12 cells. In rat models,
      bilateral ICV-STZ administration was used to produce impaired insulin signaling
      in the brain. Fourteen days following ICV-STZ injection, rats treated with twice
      daily Ex-4 had better learning and memory performance in the Morris water maze
      test compared with rats treated with saline. Additionally, histopathological
      evaluation confirmed the protective effects of Ex-4 treatment on hippocampal
      neurons against degeneration. Furthermore, we demonstrated that Ex-4 reversed ICV
      STZ-induced tau hyperphosphorylation through downregulation of GSK-3beta
      activity, a key kinase in both DM and AD. Our findings suggests that Ex-4 can
      protect neurons from diabetes-associated glucose metabolic dysregulation insults
      in vitro and from ICV-STZ insult in vivo, and that Ex-4 may prove of therapeutic
      value in the treatment of AD especially DM-related AD.

PMID- 21901365
TI  - Additional value of FDG-PET to contrast enhanced-computed tomography (CT) for the
      diagnosis of mediastinal lymph node metastasis in non-small cell lung cancer: a
      Japanese multicenter clinical study.
AB  - OBJECTIVE: This study was a controlled multicenter clinical study to verify the
      diagnostic effects of additional FDG-PET to contrast-enhanced CT for mediastinal
      lymph node metastasis in patients with operable non-small cell lung cancer
      (NSCLC). METHODS: NSCLC patients with enlarged mediastinal lymph nodes (short
      diameter, 7-20 mm), confirmed using contrast-enhanced CT, were examined using FDG
      PET to detect metastases prior to surgery. The primary endpoint was the accuracy
      for concomitantly used CT and FDG-PET showing the additional effects of FDG,
      compared with CT alone. The secondary endpoints were the clinical impact of FDG
      PET on therapeutic decisions and adverse reaction from FDG administration. The
      images were interpreted by investigators at each institution. Moreover, blinded
      readings were performed by an image interpretation committee independent of the
      institutions. The gold standard was the pathological diagnosis determined by
      surgery or biopsy after PET, and patients in whom a pathological diagnosis was
      not obtained were excluded from the analysis. RESULTS: Among 99 subjects, the
      results for 81 subjects eligible for analysis showed that the accuracy improved
      from 69.1% (56/81) for CT alone to 75.3% (61/81) for CT + PET (p = 0.404). These
      findings contributed to treatment decisions in 63.0% (51/81) of the cases, mainly
      with regard to the selection of the operative procedure. The results of the image
      interpretation committee showed that the accuracy improved from 64.2% (52/81)
      (95% CI 52.8-74.6) for CT to 75.3% (61/81) (95% CI 64.5-84.2) for CT + PET. The
      accuracy for 106 mediastinal lymph nodes improved significantly from 62.3%
      (66/106) (95% CI 52.3-71.5) for CT to 79.2% (84/106) (95% CI 70.3-86.5) for CT +
      PET (p < 0.05). We found that no serious adverse drug reactions appeared in any
      of the 99 patients who received FDG, except for transient mild outliers in the
      laboratory data for two patients. CONCLUSIONS: The addition of FDG-PET to
      contrast-enhanced CT imaging for the staging of NSCLC improved the diagnostic
      accuracy for mediastinal lymph node metastasis. FDG-PET improved the precision of
      the staging of NSCLC and contributed to the surgical decisions.

PMID- 21901366
TI  - Additional effects of FDG-PET to thin-section CT for the differential diagnosis
      of lung nodules: a Japanese multicenter clinical study.
AB  - OBJECTIVE: This study was a controlled multicenter clinical study on patients
      with peripheral lung nodules to verify the improvement in the diagnostic ability
      of FDG-PET when used in combination with thin-section CT (TS-CT). METHODS:
      Patients with peripheral lung nodules (long maximal diameter: 10-30 mm) detected
      using CT were examined using TS-CT and FDG-PET for the differential diagnosis of
      benign or malignant lesions. The primary endpoint was the specificity of the
      results using a combination of TS-CT and FDG-PET, compared with the results for
      TS-CT alone. Images were interpreted by investigators at each institution. Blind
      readings were also performed by an independent image interpretation committee.
      The gold standard was a pathological diagnosis determined using a surgical or
      biopsy specimen obtained after PET; and the patients in whom a pathological
      diagnosis could not be obtained were diagnosed based on a follow-up TS-CT
      performed more than 6 months later. Adverse reactions to FDG were also evaluated.
      RESULTS: The blind reading results for 82 lesions in 81 subjects eligible for
      analysis among the 90 subjects included in the study showed a specificity of
      91.2% (31/34) (95% CI: 76.3-98.1) for TS-CT + PET, compared with a specificity of
      67.6% (23/34) (95% CI: 49.5-82.6) for TS-CT alone. The specificity was
      significantly improved by the addition of the PET findings (p < 0.05). The
      sensitivity improved from 89.6% (43/48) for TS-CT to 91.7% (44/48) for TS-CT +
      PET; the addition of PET increased the level of confidence in the diagnosis, but
      the difference was not significant. The results reported by the institutional
      investigators were not significantly different. No serious adverse reactions
      occurred, although two of the 90 subjects exhibited mild adverse reactions.
      CONCLUSIONS: The addition of FDG-PET to TS-CT for the differential diagnosis of
      benign or malignant peripheral lung nodules resulted in a significant improvement
      in specificity. Although a definitive diagnosis of lung nodules requires a
      histopathological or cytological examination, when combined with TS-CT, FDG-PET
      can provide additional diagnostic information and improve the specificity.

PMID- 21901367
TI  - Reducing disparities: race, class and the social determinants of health.

PMID- 21901368
TI  - Increased d-dimer levels predict cardiovascular mortality in patients with
      systolic heart failure.
AB  - D-dimer is a fibrin degradation product, and is implicated in pathologies of
      cardiovascular system. Thrombosis within the vascular system in relation with
      inflammation and stasis might be associated with poor prognosis in patients with
      systolic heart failure (HF). In this study we aimed to investigate for
      relationship between d-dimer levels and cardiovascular mortality in patients with
      systolic HF. A total of 174 consecutive patients with hospitalized systolic HF
      were evaluated. All hospitalized patients were obtained d-dimer levels within the
      first 24 h following admission after obtaining informed consent. Patients were
      followed up for cardiovascular mortality and 40 (23%) patients died. d-dimer
      levels were higher among those who died compared to those who survived (2727 +/-
      2569 (710-4438) versus. 1029 +/- 1319 (303-1061) ng/ml, P < 0.001). Optimal cut
      off level of d-dimer to predict cardiovascular mortality was found to be >1435
      ng/ml. D-dimer levels were negatively correlated with ejection fraction,
      positively correlated with left atrium size and left ventricular diastolic
      diameter. D-dimer >1435 ng/ml, age, diabetes mellitus, presence of atrial
      fibrillation, and creatinine level were found to have prognostic significance in
      univariate analyses. In multivariate Cox proportional-hazards model, d-dimer >
      1435 ng/ml (HR = 3.250, 95% CI 1.647-6.414, P = 0.001), creatinine level (HR =
      1.269, 95% CI 1.008-1.599, P = 0.043), and presence of atrial fibrillation (HR =
      2.159, 95% CI 1.047-4.452, P = 0.037) remained associated with an increased risk
      of death after adjustment for variables found to be statistically significant in
      univariate analysis and correlated with d-dimer level. In conclusion, d-dimer
      measurement could help risk stratification in patients with systolic HF.

PMID- 21901369
TI  - Fermentative hydrogen production from soybean protein processing wastewater in an
      anaerobic baffled reactor (ABR) using anaerobic mixed consortia.
AB  - Fermentative H(2) production from soybean protein processing wastewater (SPPW)
      was investigated in a four-compartment anaerobic baffled reactor (ABR) using
      anaerobic mixed cultures under continuous flow condition in the present study.
      After being inoculated with aerobic activated sludge and operated at the
      inoculants of 5.98 gVSS L(-1), COD of 5000 mg L(-1), HRT of 16 h and temperature
      of (35 +/- 1)  degrees C for 22 days, the ABR achieved stable ethanol-type
      fermentation. The specific hydrogen production rate of anaerobic activated sludge
      was 165 LH(2)kg MLVSS(-1) day(-1), the substrate conversion rate was 600.83
      LH(2)kg COD(-1)and the COD removal efficiency was 44.73% at the stable operation
      status. The ABR system exhibited a better stability and higher hydrogen yields
      than continuous stirring tank reactor under the same operational condition. The
      experimental data documented the feasibility of substrate degradation along with
      molecular H(2) generation utilizing SPPW as primary carbon source in the ABR
      system.

PMID- 21901370
TI  - Characterization and identification of a chymotryptic hydrolysate of alpha
      lactalbumin stimulating cholecystokinin release in STC-1 cells.
AB  - Alpha-lactalbumin hydrolysate is of significant interest, due to its potential
      application as a source of bioactive peptides in nutraceutical and pharmaceutical
      domains. This study was focused on the cholecystokinin (CCK) family compounds
      which are small peptides involved in the satiety control. The action of
      chymotryptic hydrolysate of alpha-lactalbumin on cholecystokinin release from
      intestinal endocrine STC-1 cells was investigated. We demonstrated for the first
      time that a chymotryptic hydrolysate of alpha-lactalbumin was able to highly
      stimulate CCK-releasing activity from STC-1 cells. The peptidic hydrolysate was
      characterized by LC/MS and MS/MS, thus highlighting the presence of 11 fractions
      containing 21 peptides, each potentially having the desired activity.

PMID- 21901371
TI  - Evaluation of trabecular bone formation in a canine model surrounding a dental
      implant fixture immobilized with an antimicrobial peptide derived from histatin.
AB  - JH8194 induces osteoblast differentiation, although it was originally designed to
      improve antifungal activity. This suggests that JH8194 is useful for implant
      treatment. Therefore, the aim of this study was to evaluate the osseointegration
      capacity of JH8194-modified titanium dental implant fixtures (JH8194-Fi). The
      implants were randomly implanted into the edentulous ridge of dog mandibles.
      Healing abutments were inserted immediately after implant placement. Three weeks
      later, peri-implant bone levels, the first bone-to-implant contact points, and
      trabecular bone formation surrounding the implants were assessed by histological
      and digital image analyses based on microcomputed tomography (microCT). The
      histological analysis revealed an enhancement of mature trabecular bone around
      the JH8194-Fi compared with untreated fixtures (control-Fi). Similarly, microCT
      combined with analysis by Zed ViewTM also showed increased trabecular bone
      formation surrounding the JH8194-Fi compared with the control-Fi (Student's t
      test, P < 0.05). JH8194 may offer an alternative biological modification of
      titanium surfaces to enhance trabecular bone formation around dental implants,
      which may contribute to the transient acquirement of osseointegration and the
      long-term success of implant therapy.

PMID- 21901372
TI  - Superporous polyacrylate/chitosan IPN hydrogels for protein delivery.
AB  - In this study, poly(acrylamide), poly(AAm), and poly(acrylamide-co-acrylic acid),
      poly(AAm-co-AA) superporous hydrogels (SPHs) were synthesized by radical
      polymerization in the presence of gas blowing agent, sodium bicarbonate. In
      addition, ionically crosslinked chitosan (CH) superporous hydrogels were
      synthesized to form interpenetrating superporous hydrogels, i.e. poly(AAm)-CH and
      poly(AAm-co-AA)-CH SPH-IPNs. The hydrogels have a structure of interconnected
      pores with pore sizes of approximately 100-150 MUm. Although the extent of
      swelling increased when AA were incorporated to the poly(AAm) structure, the time
      to reach the equilibrium swelling (~30 s) was not affected so much. In the
      presence of chitosan network mechanical properties significantly improved when
      compared with SPHs, however, equilibrium swelling time (~30 min) was prolonged
      significantly as due to the lower porosities and pore sizes of SPH-IPNs than that
      of SPHs. Model protein bovine serum albumin (BSA) was loaded into SPHs and SPH
      IPNs by solvent sorption in very short time (<1 h) and very high capacities (~30
      300 mg BSA/g dry gel) when compared to conventional hydrogels. BSA release
      profiles from SPHs and SPH-IPNs were characterized by an initial burst of protein
      during the first 20 min followed by a completed release within 1 h. However,
      total releasable amount of BSA from SPH-IPNs was lower than that of SPHs as due
      to the electrostatic interactions between chitosan and BSA.

PMID- 21901373
TI  - Salinarchaeum laminariae gen. nov., sp. nov.: a new member of the family
      Halobacteriaceae isolated from salted brown alga Laminaria.
AB  - Halophilic archaeal strains R26(T) and R22 were isolated from the brown alga
      Laminaria produced at Dalian, Liaoning Province, China. Cells from the two
      strains were pleomorphic rods and Gram negative, and colonies were red pigmented.
      Strains R26(T) and R22 were able to grow at 20-50 degrees C (optimum 37 degrees
      C) in 1.4-5.1 M NaCl (optimum 3.1-4.3 M) at pH 5.5-9.5 (optimum pH 8.0-8.5) and
      neither strain required Mg(2+) for growth. Cells lyse in distilled water and the
      minimum NaCl concentration required to prevent cell lysis was 8% (w/v) for strain
      R26(T) and 12% (w/v) for strain R22. The major polar lipids of the two strains
      were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and minor
      phosphatidylglycerol sulfate; glycolipids were not detected. Phylogenetic
      analyses based on 16S rRNA genes and rpoB' genes revealed that strains R26(T) and
      R22 formed a distinct clade with the closest relative, Natronoarchaeum
      mannanilyticum. The DNA G+C content of strains R26(T) and R22 was 65.8 and 66.4
      mol%, respectively. The DNA-DNA hybridization value between strains R26(T) and
      R22 was 89%. The phenotypic, chemotaxonomic and phylogenetic properties suggest
      that the strains R26(T) and R22 represent a novel species in a new genus within
      the family Halobacteriaceae, for which the name Salinarchaeum laminariae gen.
      nov., sp. nov. is proposed. The type strain is R26(T) (type strain R26(T) = CGMCC
      1.10590(T) = JCM 17267(T), reference strain R22 = CGMCC 1.10589).

PMID- 21901374
TI  - Fetus in fetu from newborn's mediastinum: case report and a review of literature.
AB  - Fetus in fetu is a rare congenital anomaly, when the malformed monozygotic twin
      is found within the body of a living child or sometimes in an adult. We report a
      case of fetus in fetu diagnosed during the early third trimester of pregnancy, in
      the medial and inferior portions of anterior mediastinum of the dominant twin.
      The diagnosis was suspected by prenatal ultrasound and fetal magnetic resonance
      imaging. It was postnatally confirmed by CT and RTG, surgically removed after
      birth and histologically examined. Histologically we found well-developed organs
      and tissues derived from all germ layers. To our knowledge, we describe the
      fourth case of fetus in fetu located in the thorax, and the second case located
      in the anterior mediastinum. This case highlights the usefulness of prenatal
      ultrasound and MRI in the diagnosis of mediastinal masses, and the usefulness of
      complete histological examination for confirmation of diagnosis of fetus in fetu.
      We also reviewed the possible embryologic backgrounds of this congenital anomaly.

PMID- 21901375
TI  - Vertebral arteria lusoria: a life-threatening condition for oesophageal surgery.
AB  - A rare anatomic variant of the right vertebral artery is reported as an
      incidental finding in a 78-year-old female patient. The vessel originated from
      the aortic arch distal to the origin of the left subclavian artery and presented
      an unusual retroesophageal course, thus was named "vertebral arteria lusoria". As
      multi-detector row computed tomography examination is now widely used, this
      anatomical variant should be considered in any patient undergoing esophageal
      surgery. Misdiagnosis of such an aberrant vertebral artery may cause life
      threatening issues.

PMID- 21901376
TI  - Persistent primitive olfactory artery.

PMID- 21901377
TI  - The effectiveness of psychosocial interventions designed to improve health
      related quality of life (HRQOL) amongst asthmatic children and their families: a
      systematic review.
AB  - PURPOSE: Asthmatic children are at risk of compromised health-related quality of
      life (HRQOL) compared with their healthy peers. This systematic review reports
      the range and effectiveness of psychosocial interventions designed to improve
      HRQOL amongst asthmatic children, adolescents, and their families. METHOD: Data
      sources included The Cochrane Airways Group Trials Register of trials, PubMed
      database, and reference lists from review articles. RESULTS: Eighteen studies of
      psychosocial interventions were identified. Interventions were designed to
      improve HRQOL amongst a range of psychosocial, health care, school-related and
      clinical outcomes, and were delivered in numerous settings and formats. Four
      studies reported that interventions were effective for significant improvements
      in child overall HRQOL scores. These include asthma education (n = 2), asthma
      education plus problem solving (n = 1), and art therapy (n = 1). CONCLUSIONS:
      Most interventions focussed on the delivery of asthma education to children, with
      the purpose of improving knowledge about asthma and disease management. There is
      limited evidence to suggest that interventions currently available are effective
      for significantly improving HRQOL amongst asthmatic children, adolescents, and
      their families. Most interventions lacked a theoretical basis and did not focus
      on family functioning variables. Multi-component interventions that incorporate
      asthma education along with strategies to assist families with implementing
      behaviour change towards improved asthma management are required. Future
      interventions should also attempt to address the wider context of family
      functioning likely to contribute to the family's ability to engage in successful
      asthma management in order to improve HRQOL.

PMID- 21901378
TI  - Using mixed methods research to explore the effect of an adaptation exercise on
      general population valuations of health states.
AB  - PURPOSE: To understand the effect of an adaptation exercise (AE) on general
      population values for rheumatoid arthritis (RA) states. METHODS: A sequential
      mixed methods design was employed: an analysis of a dataset to develop RA states
      for valuing in later phases of the study; a qualitative interview study with
      members of the general population to identify how an AE affected valuing of the
      RA states and to help design a questionnaire for the final phase; and a
      quantitative quasi-experimental study to identify factors that influence change
      in values after being informed about adaptation. RESULTS: Three RA states were
      developed using Rasch and cluster analyses. Participants in the qualitative phase
      identified a range of ways in which information about adaptation affected their
      values. For example, they realized they could adapt to RA because their family
      and friends who had RA, or similar conditions, could cope. A 25-item
      questionnaire was developed and used during the final phase to identify that
      younger and healthier individuals were more likely to increase their values after
      being informed about disease adaptation. The qualitative findings were revisited
      and found to support the quantitative results. CONCLUSIONS: This approach
      facilitated understanding of whether and how an AE affected valuing of health
      states. Each phase affected the next phase of the study, leading to the
      conclusion that general population respondents who have little experience of
      disease will likely increase their health state values after being informed about
      adaptation because they understand that they could cope with the disease.

PMID- 21901379
TI  - Septic pulmonary embolisms and metastatic infections from methicillin-resistant
      Staphylococcus aureus endocarditis on FDG PET/CT.

PMID- 21901380
TI  - Do we have to withdraw antiandrogenic therapy in prostate cancer patients before
      PET/CT with [11C]choline?

PMID- 21901382
TI  - Are we ready for an early evaluation of the response of axillary lymph node
      metastases to neoadjuvant therapy?

PMID- 21901383
TI  - Activity quantification combining conjugate-view planar scintigraphies and
      SPECT/CT data for patient-specific 3-D dosimetry in radionuclide therapy.
AB  - PURPOSE: Three-dimensional dosimetry based on quantitative SPECT/CT has potential
      advantages over planar approaches, but may be impractical due to acquisition
      durations. We combine one SPECT/CT with improved quantification of multiple
      planar scintigraphies to shorten acquisitions. METHODS: A hybrid 2-D/3-D
      quantification technique is proposed, using SPECT/CT information for robust
      planar image quantification and creating virtual SPECTs out of conjugate-view
      planar scintigraphies; these are included in a 3-D absorbed dose calculation. A
      projection model simulates photon attenuation and scatter as well as camera and
      collimator effects. Planar and SPECT calibration techniques are described,
      offering multiple pathways of deriving calibration factors for hybrid
      quantification. Model, phantom and patient data are used to validate the approach
      on a per-organ basis, and the similarity of real and virtual SPECTs, and of
      planar images and virtual SPECT projections, is assessed using linear regression
      analysis. RESULTS: Organ overlap, background activity and organ geometry are
      accounted for in the algorithm. Hybrid time-activity curves yield the same
      information as those derived from a conventional SPECT evaluation. Where correct
      values are known, hybrid quantification errors are less than 16% for all but two
      compartments (SPECT/CT 23%). Under partial volume effects, hybrid quantification
      can provide more robust results than SPECT/CT. The mean correlation coefficient
      of 3-D data is 0.962 (2-D 0.934). As a consequence of good activity
      quantification performance, good agreement of absorbed dose estimates and dose
      volume histograms with reference results is achieved. CONCLUSION: The proposed
      activity quantification method for 2-D scintigraphies can speed up SPECT/CT-based
      3-D dosimetry without losing accuracy.

PMID- 21901381
TI  - Emerging roles for integrated imaging modalities in cardiovascular cell-based
      therapeutics: a clinical perspective.
AB  - Despite preclinical promise, the progress of cell-based therapy to clinical
      cardiovascular practice has been slowed by several challenges and uncertainties
      that have been highlighted by the conflicting results of human trials. Most
      telling has been the revelation that current strategies fall short of achieving
      sufficient retention and engraftment of cells to meet the ambitious objective of
      myocardial regeneration. This has sparked novel research into the refinement of
      cell biology and delivery to overcome these shortcomings. Within this context,
      molecular imaging has emerged as a valuable tool for providing noninvasive
      surveillance of cell fate in vivo. Direct and indirect labelling of cells can be
      coupled with clinically relevant imaging modalities, such as radionuclide single
      photon emission computed tomography and positron emission tomography, and
      magnetic resonance imaging, to assess their short- and long-term distributions,
      along with their viability, proliferation and functional interaction with the
      host myocardium. This review details the strengths and limitations of the
      different cell labelling and imaging techniques and their potential application
      to the clinical realm. We also consider the broader, multifaceted utility of
      imaging throughout the cell therapy process, providing a discussion of its
      considerable value during cell delivery and its importance during the evaluation
      of cardiac outcomes in clinical studies.

PMID- 21901384
TI  - Changes in perceived attentional function in women following breast cancer
      surgery.
AB  - After treatment for breast cancer, many women experience cognitive problems, as
      determined by objective neuropsychological tests. However, the ecological
      validity of these tests has been questioned. This study explored the trajectory
      of perceived attentional function from before to 24 months after surgery in women
      with breast cancer and examined the effect of adjuvant treatment on this
      perceived attentional function. Women with breast cancer (N = 200) were assessed
      for perceived cognitive function by measuring attentional function using the
      attentional function index (AFI). Covariates included anxiety, depression,
      fatigue, and sleep disturbance. Perceived attentional function declined in 54% of
      women at 1 month after surgery. At 1 and 2 years after surgery, 41 and 30% of
      women, respectively, still perceived this decline. The mean AFI decreased to the
      lowest point 1 month after surgery, but improved gradually afterward, taking
      about 1 year to return to the pre-surgery level. Decreases in perceived
      attentional function were associated with increases in anxiety, depression,
      fatigue, and sleep disturbance. After controlling for baseline differences and
      covariates, mean AFI scores were not associated with adjuvant treatment.
      Perceived cognitive function deteriorated after surgery but improved over time.
      It was not associated with adjuvant cancer treatment.

PMID- 21901386
TI  - Smac-mimetic compound SM-164 induces radiosensitization in breast cancer cells
      through activation of caspases and induction of apoptosis.
AB  - Radiotherapy is a treatment choice for local control of breast cancer,
      particularly after the removal of tumor tissues by surgery. However, intrinsic
      radioresistance of cancer cells limits therapeutic efficacy. Here, we determined
      in breast cancer cells the potential radiosensitizing activity of SM-164, a small
      molecule compound, that mimics the activity of SMAC, a mitochondrial protein
      released during apoptosis to activate caspases by inhibiting cellular inhibitor
      of apoptosis proteins, cIAP-1, and XIAP. We found that SM-164 at nanomolar
      concentrations promoted degradation of cIAP-1, disrupted the inhibitory binding
      of XIAP to active caspase-9, and sensitized breast cancer cells to radiation with
      a sensitization enhancement ratio (SER) of 1.7-1.8. In one line of breast cancer
      cells resistant to SM-164 as a single agent, SM-164 radiosensitization was
      mediated by intrinsic apoptosis pathway through activation of caspases-9 and -3.
      In a line of breast cancer cells sensitive to SM-164 as a single agent, SM-164
      radiosensitization was mediated by both extrinsic and intrinsic apoptosis
      pathways through activation of caspases-9, -8, and -3. Consistently, blockage of
      caspase activation, through siRNA knockdown or treatment with a pan-caspase
      inhibitor z-VAD-fmk, inhibited apoptosis and abrogated SM-164 radiosensitization.
      Our study demonstrates that IAPs are valid radiosensitizing targets in breast
      cancer cells and SM-164 could be further developed as a novel class of
      radiosensitizers for the treatment of radioresistant breast cancer.

PMID- 21901385
TI  - Effect of anti-DR5 and chemotherapy on basal-like breast cancer.
AB  - The purpose is to evaluate sensitivity of basal-like breast cancer to treatment
      with anti-DR5 alone and in combination with chemotherapy. Cytotoxicity of TRA-8
      anti-DR5 alone and in combination with doxorubicin or paclitaxel was examined.
      The role of a DR5-associated molecule (DDX3) in the regulation of apoptosis by
      recruitment of cIAP1 to the DR5/DDX3 complex was studied. SUM159 and 2LMP
      orthotopic xenografts were treated with TRA-8 alone and in combination with
      Abraxane or doxorubicin, and tumor growth inhibition determined. Diffusion
      weighted magnetic resonance imaging was used to monitor early tumor response. The
      majority (12/15) of basal-like cell lines were very sensitive to TRA-8-induced
      cytotoxicity (IC(50) values of 1.0-49 ng/ml). In contrast, 8/11 luminal or HER2
      positive cell lines were resistant (IC(50) > 1,000 ng/ml). Enhanced killing of
      basal-like cell lines was produced by combination treatment with TRA-8 and
      doxorubicin. Majority of basal cell lines expressed lower levels of DR5
      associated DDX3 and cIAP1 than luminal and HER2-positive cell lines. TRA-8
      inhibited growth of basal xenografts and produced 20% complete 2LMP tumor
      regressions. TRA-8 and chemotherapy produced greater 2LMP growth inhibition than
      either alone. An increase in apparent diffusion coefficient in 2LMP tumors was
      measured in a week of therapy with TRA-8 and Abraxane. Basal-like cell lines were
      more sensitive to TRA-8-mediated cytotoxicity than HER2-over-expressing and
      luminal cell lines, and chemotherapy enhanced cytotoxicity. High sensitivity of
      basal cells to TRA-8 correlated with low expression of DR5/DDX3/cIAP1 complex.
      Treatment with TRA-8 and chemotherapy may be an effective therapy for basal-like
      breast cancer.

PMID- 21901387
TI  - The role of caveolin-1 in human breast cancer.
AB  - Caveolin-1 is the essential constituent protein of specialised plasma membrane
      invaginations called caveolae. The unique topology of caveolin-1 facilitates the
      role of caveolae as molecular hubs, integrating the activity of a multitude of
      signalling molecules. Despite improvements in our understanding of caveolin-1
      interactions and the function of caveolae, the relationship between dysfunctional
      caveolin-1 and tumourigenesis remains contentious. Perhaps most intriguing has
      been the demonstration of both oncogenic and tumour suppressor function within
      particular tumour types, including breast cancer. In this review, the biological
      and clinical relevance of caveolin-1 in human breast cancer are considered.
      Evidence is systematically presented for the potential tumour suppressor and
      oncogenic functions of caveolin-1. Specific reference is made to interactions
      between caveolin-1 and signalling pathways in the clinical and biological
      subtypes of breast cancer. Areas of controversy are discussed and technical
      considerations are highlighted. Translational implications and potential for
      specific therapeutic manipulation of caveolin-1 are evaluated in the context of
      evidence from in vitro and in vivo studies.

PMID- 21901388
TI  - Genetic heterogeneity in HER2 testing may influence therapy eligibility.
AB  - Prospective studies have demonstrated that approximately 20% of HER2 testing may
      be inaccurate. When carefully validated testing is conducted, available data do
      not clearly demonstrate the superiority of either IHC or fluorescence in situ
      hybridization (FISH) as a predictor of benefit from anti-HER2 therapy. In
      addition, the interpretation of the findings of HER2 tests according to
      international guidelines is not uniform. The American Society of Clinical
      Oncology (ASCO) and the College of American Pathologists (CAP) recently published
      practice guidelines for a definition of HER2 amplification heterogeneity that can
      give rise to discrepant results between IHC and FISH assays for HER2. In this
      article, we compare the HER2 status of 291 non consecutive breast cancers. The
      status is determined by both IHC and FISH approaches, using a specific FISH
      strategy to investigate genetic heterogeneity. Our data demonstrate that HER2
      amplified cells may be found as diffuse, clustered in a specific area or section,
      intermingled with non-amplified cells or confined to metastatic nodules. The
      correct evaluation of ratio value in the presence of genetic heterogeneity and of
      polysomy contributes to the accurate assessment of HER2 status and potentially
      affects the selection of appropriate anti-HER2 therapy. By taking into account
      the presence of different genetic cell populations, the immunotherapy eligibility
      criteria for HER2 FISH scoring proposed in the CAP (2009) and SIGU guidelines
      identify an additional subset of cases for trastuzumab or lapatinib therapy
      compared to the ASCO/CAP (2007) guidelines.

PMID- 21901389
TI  - The effects of mindfulness-based stress reduction on psychosocial outcomes and
      quality of life in early-stage breast cancer patients: a randomized trial.
AB  - The aim of this study was determine the effectiveness of a mindfulness-based
      stress-reduction (MBSR) program on quality of life (QOL) and psychosocial
      outcomes in women with early-stage breast cancer, using a three-arm randomized
      controlled clinical trial (RCT). This RCT consisting of 172 women, aged 20-65
      with stage I or II breast cancer consisted of the 8-week MBSR, which was compared
      to a nutrition education program (NEP) and usual supportive care (UC). Follow-up
      was performed at three post-intervention points: 4 months, 1, and 2 years.
      Standardized, validated self-administered questionnaires were adopted to assess
      psychosocial variables. Statistical analysis included descriptive and regression
      analyses incorporating both intention-to-treat and post hoc multivariable
      approaches of the 163 women with complete data at baseline, those who were
      randomized to MBSR experienced a significant improvement in the primary measures
      of QOL and coping outcomes compared to the NEP, UC, or both, including the
      spirituality subscale of the FACT-B as well as dealing with illness scale
      increases in active behavioral coping and active cognitive coping. Secondary
      outcome improvements resulting in significant between-group contrasts favoring
      the MBSR group at 4 months included meaningfulness, depression, paranoid
      ideation, hostility, anxiety, unhappiness, and emotional control. Results tended
      to decline at 12 months and even more at 24 months, though at all times, they
      were as robust in women with lower expectation of effect as in those with higher
      expectation. The MBSR intervention appears to benefit psychosocial adjustment in
      cancer patients, over and above the effects of usual care or a credible control
      condition. The universality of effects across levels of expectation indicates a
      potential to utilize this stress reduction approach as complementary therapy in
      oncologic practice.

PMID- 21901390
TI  - Carotenoids and breast cancer risk: a meta-analysis and meta-regression.
AB  - The purpose of this article is to comprehensively summarize the associations
      between carotenoids and breast cancer and quantitatively estimate their dose
      response relationships. We searched PubMed, Embase, and Cochrane databases (from
      January 1982 to 1 May 2011) and the references of the relevant articles in
      English with sufficient information to estimate relative risk or odds ratio and
      the 95% confidence intervals, and comparable categories of carotenoids. Two
      reviewers independently extracted data using a standardized form; with any
      discrepancy adjudicated by the third reviewer. 33 studies met the inclusion
      criteria. Comparing the highest with the lowest intake: dietary alpha-carotene
      intake significantly reduced the breast cancer risk by 9.0% (pooled RR = 0.91;
      95% CI: 0.85-0.98; P = 0.01), dietary beta-carotene intake reduced the risk by
      6.0% (pooled RR = 0.94; 95% CI: 0.88-1.00; P = 0.05); total beta-carotene intake
      reduced the risk by 5.0% (pooled RR = 0.95; 95% CI: 0.90-1.01; P = 0.08) when
      data from cohort studies were pooled. Significant dose-response relationships
      were observed in both the higher intake of dietary and total beta-carotene with
      reduced breast cancer risk when data from cohort studies (P (trend) < 0.01, P
      (trend) = 0.03) and case-control studies (P (trend) < 0.01, P (trend) < 0.01)
      were pooled, respectively. Dietary alpha-carotene intake could reduce the breast
      cancer risk. The relationships between dietary and total beta-carotene intake and
      breast cancer need to be confirmed. No significant association between dietary
      intake of beta-cryptoxanthin, lutein/+zeaxanthin, and lycopene and breast cancer
      was observed.

PMID- 21901391
TI  - Role of CD44 in lymphokine-activated killer cell-mediated killing of melanoma.
AB  - In the current study, we examined the potential significance of CD44 expression
      on lymphokine-activated killer (LAK) cells in their interaction and killing of
      melanoma cells. Stimulation of splenocytes with IL-2 led to a significant
      increase in the expression of CD44 on T cells, NK cells, and NKT cells. Treatment
      of melanoma-bearing CD44 WT mice with IL-2 led to a significant reduction in the
      local tumor growth while treatment of melanoma-bearing CD44 KO mice with IL-2 was
      ineffective at controlling tumor growth. Furthermore, the ability of splenocytes
      from IL-2-treated CD44 KO mice to kill melanoma tumor targets was significantly
      reduced when compared to the anti-tumor activity of splenocytes from IL-2-treated
      CD44 WT mice. The importance of CD44 expression on the LAK cells was further
      confirmed by the observation that adoptively transferred CD44 WT LAK cells were
      significantly more effective than CD44 KO LAK cells at controlling tumor growth
      in vivo. Next, the significance of the increased expression of CD44 in tumor
      killing was examined and showed that following stimulation with IL-2, distinct
      populations of cells with low (CD44(lo)) or elevated (CD44(hi)) expression of
      CD44 are generated and that the CD44(hi) cells are responsible for killing of the
      melanoma cells. The reduced killing activity of the CD44 KO LAK cells did not
      result from reduced activation or expression of effector molecules but was due,
      at least in part, to a reduced ability to adhere to B16F10 tumor cells.

PMID- 21901392
TI  - Detection and evaluation of normal and malignant cells using laser-induced
      fluorescence spectroscopy.
AB  - The aim of this research is to study the normalized fluorescence spectra
      (intensity variations and area under the fluorescence signal), relative quantum
      yield, extinction coefficient and intracellular properties of normal and
      malignant human bone cells. Using Laser-Induced Fluorescence Spectroscopy (LIFS)
      upon excitation of 405 nm, the comparison of emission spectra of bone cells
      revealed that fluorescence intensity and the area under the spectra of malignant
      bone cells was less than that of normal. In addition, the area ratio and shape
      factor were changed. We obtained two emission bands in spectra of normal cells
      centered at about 486 and 575 nm and for malignant cells about 482 and 586 nm
      respectively, which are most likely attributed to NADH and riboflavins. Using
      fluorescein sodium emission spectrum, the relative quantum yield of bone cells is
      numerically determined.

PMID- 21901393
TI  - T-cell compartment in synovial fluid of pediatric patients with JIA correlates
      with disease phenotype.
AB  - INTRODUCTION: Juvenile idiopathic arthritis (JIA) is an autoimmune disease where
      T cells are key players. It can be classified into two main clinical diseases:
      polyarticular and pauciarticular, based on the number of joints involved.
      Oligoarthritis, which is considered a pauciarticular subtype since it involves up
      to four joints upon presentation, is further divided into persistent or extended
      forms based on disease progression. METHODOLOGY/PRINCIPAL FINDINGS: Here we
      assessed the T-cell compartment in synovial fluid obtained from 33 JIA patients
      with active disease and correlated the analyzed parameters with the patients'
      clinical characteristics. The T-cell compartment was determined by the
      representation of T-cell receptor (TCR) repertoires and the amount of TCR
      excision circles (TRECs). RESULTS: Patients with polyarticular disease have more
      a clonal pattern of their TCR repertoire. These findings were consistent in all
      tested TCR-Vgamma consensus primers. Similarly, patients with polyarticular
      disease had lower TREC levels than patients with pauciarticular disease. A
      predictive value of TRECs may be suggested, as lower TREC levels were observed in
      patients in whom disease modifying anti rheumatic drugs were initiated
      subsequently during the follow-up. CONCLUSION: In pediatric JIA patients, we
      showed an alteration in the T cells from synovial fluid, which correlated with
      disease phenotype, assumedly secondary to enhanced proliferation, clonal TCR
      restriction, and reduced T-cell production, possibly reflecting a different
      disease or a different course of disease progression.

PMID- 21901394
TI  - Impaired peripheral Th1 CD4+ T cell response to Escherichia coli proteins in
      patients with Crohn's disease and ankylosing spondylitis.
AB  - BACKGROUND: To clarify the impact of T cell responses towards enteric antigens
      for chronic intestinal inflammation, we determined T helper 1 reactivity towards
      conserved Escherichia coli proteins in patients with Crohn's disease (CD) and
      healthy individuals and patients with ankylosing spondylitis (AS), who also often
      show microscopic inflammatory lesions within the gut or even develop overt
      inflammatory bowel disease. METHODS: We determined the frequency of
      IFNgamma+CD40L+ cells/CD4+ T cells after stimulation of whole blood with pools of
      E. coli proteins. RESULTS: The E. coli-specific Th1 response was significantly
      reduced in CD patients and to a lower extent also in AS patients. CONCLUSIONS: E.
      coli is a target for polyclonal Th1 responses in healthy individuals. The
      impairment of these responses in CD and AS patients might be due to recruitment
      of enterobacteria-specific Th1 cells to the gut or might reflect inadequate
      priming of adaptive immune response.

PMID- 21901395
TI  - Triple-negative phenotype is of adverse prognostic value in patients treated with
      dose-dense sequential adjuvant chemotherapy: a translational research analysis in
      the context of a Hellenic Cooperative Oncology Group (HeCOG) randomized phase III
      trial.
AB  - PURPOSE: It is well recognized that breast cancer is a heterogeneous disease. The
      purpose of the current study was to classify patients according to the
      immunohistochemical phenotype of their tumors in an effort to evaluate the
      outcome of the respective groups of patients and specifically of those with
      triple-negative breast cancer (TNBC) following dose-dense sequential adjuvant
      chemotherapy. METHODS: A total of 595 patients with high-risk breast cancer were
      treated with adjuvant anthracycline-based dose-dense sequential chemotherapy with
      or without paclitaxel in the context of a randomized study. ER, PgR, HER2, Ki67,
      EGFR, and CK5 protein expression were evaluated in 298 formalin-fixed paraffin
      embedded tumor samples by immunohistochemistry (IHC). HER2 was also evaluated by
      chromogen in situ hybridization (CISH). HER2 status and Ki67 protein expression
      differentiated luminal IHC subtypes (luminal B tumors being HER2 and/or Ki67
      positive). RESULTS: Among the 298 tumors, the immunohistochemical panel
      classified 37 (12%) as luminal A, 198 (66%) as luminal B, 27 (9%) as HER2
      enriched, and 36 (12%) as TNBC. The median follow-up time was 97 months. Patients
      with luminal A tumors had the best prognosis, with improved disease-free survival
      (log-rank, P = 0.033) and overall survival (P = 0.006) compared with the other
      three tumor subtypes. The three subtypes had an increased risk for relapse and
      death compared with luminal A in multivariate analysis, as well. No benefit from
      paclitaxel treatment was detected in any of the four subtypes or the total
      cohort. Hierarchical clustering based on mRNA expression of ER, PgR, and HER2 by
      quantitative RT-PCR identified patient groups that were comparable to the
      subtypes identified by IHC. CONCLUSIONS: The results of this study confirm that
      triple negative, luminal B and HER2-enriched phenotypes identified by IHC are of
      adverse prognostic value in high-risk breast cancer patients treated with dose
      dense sequential adjuvant chemotherapy.

PMID- 21901396
TI  - A phase I study of 5-azacytidine and erlotinib in advanced solid tumor
      malignancies.
AB  - INTRODUCTION: The epidermal growth factor receptor (EGFR) is a validated target
      in malignancy; however, patients with wild type EGFR obtain little sustained
      benefit from anti-EGFR monotherapy. Epigenetic therapy to reactivate tumor
      suppressor genes may enhance the anti-proliferative effect of erlotinib. This
      phase I study evaluated the combination of erlotinib and 5-azacytidine for safety
      and maximal tolerated dose (MTD). METHODS: Thirty patients with advanced solid
      tumors were treated in a standard 3 + 3 cohort design. Erlotinib was dosed at 150
      mg daily, and 5-azacytidine was escalated by increasing the number of daily doses
      of 75 mg/m(2) per cycle. Patients were followed for dose-limiting toxicity (DLT).
      Efficacy was assessed by RECIST criteria. RESULTS: Common non-hematologic
      toxicities included rash, diarrhea, nausea, and fatigue; the majority was <=
      Grade 2. DLTs included conjunctivitis in cohort 1 and infusion reaction in cohort
      2. No DLTs occurred in cohorts 3, 4, or 5; however, 2 serious neutropenic
      infections arose in cohort 5 after cycle 1. Cohort 4 was expanded to 6 patients
      and was the MTD. Partial response (lung, ovarian) and stable disease occurred in
      2 and 11 patients, respectively. Median progression-free survival was 2 months.
      Two patients with lung and larynx cancer had prolonged stable disease.
      CONCLUSION: The combination of erlotinib and 5-azacytidine was well tolerated
      with interesting clinical activity in lung, head and neck, and ovarian cancer.
      The recommended dose for phase II study is erlotinib 150 mg daily and 5
      azacytidine 75 mg/m(2) daily on days 1-4 and 15-18 of a 28-day cycle.

PMID- 21901397
TI  - The predictive value of human organic cation transporter 1 and ABCB1 expression
      levels in different cell populations of patients with de novo chronic myelogenous
      leukemia.

PMID- 21901399
TI  - Long-term pattern of pleural effusion from chronic myeloid leukemia patients in
      second-line dasatinib therapy.
AB  - Dasatinib is a potent second-generation tyrosine kinase inhibitor approved for
      the treatment of chronic myeloid leukemia after imatinib failure. However, some
      patients treated with dasatinib experience pleural effusions (PEs). The
      determinants of pleural effusion in long-term dasatinib treatment (median 35
      months, range 1-55) were investigated in single-center data of 65 patients
      enrolled in global phase 2 and phase 3 trials. Of the 65 patients, 35 (54%)
      developed dasatinib-induced pleural effusion (a median onset time, 20 months;
      range 0.2-54). The first pleural effusion developed in 15 (43%) patients within
      12 months of dasatinib therapy. Disease phase (P = 0.02), dose schedule (P =
      0.002) and actual daily mean dose (P = 0.0002) were significantly associated with
      an increased risk of pleural effusion. Twice-daily administration of dasatinib
      resulted in significantly more patients developing pleural effusions compared
      with the once-daily dosing schedule, particularly in advanced disease. In
      addition, a strong correlation was found between actual daily mean dose and time
      to onset of pleural effusions in patients treated with a daily mean dose >100
      mg/day of dasatinib (P = 0.01). These data emphasize the need for dasatinib dose
      and schedule optimization and long-term monitoring of dasatinib-treated patients
      to prevent the negative clinical implications of pleural effusion.

PMID- 21901398
TI  - MicroRNA-146a and hemopoietic disorders.
AB  - MicroRNAs (MiRNAs) are a class of small non-coding regulatory RNAs that repress
      protein expression at the posttranscriptional level and play important roles in
      hematopoiesis processes. MiR-146a is a miRNA that is thought to regulate
      physiological and pathophysiological pathways in hematopoietic cells. In this
      review, we focus on recent progress in analyzing the functional roles of miR-146a
      in normal hematopoiesis and hematopoietic disease. We suggest that manipulation
      of miR-146a expression may represent a potential new therapy for several
      hematopoietic diseases, and may further serve as a biomarker for diagnosis,
      prevention, and treatment of such disease.

PMID- 21901400
TI  - The age at onset of psychosis and tobacco use: a systematic meta-analysis.
AB  - BACKGROUND: There is a well-established but poorly understood association between
      tobacco use and psychotic illness. The aim of this study was to determine whether
      tobacco use is associated with an earlier age at onset of psychotic illness.
      METHODS: Peer-reviewed publications in English reporting the age at onset of
      psychosis in tobacco-using and non-tobacco-using groups were located using
      searches of CINAHL, EMBASE, MEDLINE, PsycINFO and ISI Web of Science, and were
      supplemented by papers located by manual searches and unpublished data obtained
      by correspondence with primary researchers. A total of 29 samples reported age at
      onset data in a consecutive series of patients with a diagnosis of schizophrenia
      related psychosis or first episode psychosis. Information on study design, study
      population and effect size was extracted independently by three authors. A random
      effects meta-analysis was performed. RESULTS: There was no significant difference
      between smokers and non-smokers in age at the onset of psychosis (standardized
      mean difference = -0.03). CONCLUSION: Unlike cannabis use, tobacco use is not
      associated with an earlier onset of psychosis.

PMID- 21901401
TI  - Depression literacy among Chinese in Shanghai, China: a comparison with Chinese
      speaking Australians in Melbourne and Chinese in Hong Kong.
AB  - OBJECTIVE: The study reported in this paper was aimed at developing understanding
      of depression-related knowledge and preferences surrounding professional help,
      medication, and treatment methods among Chinese living in Shanghai, China.
      METHODS: A multi-stage cluster sampling method in which participants were taken
      from 6 of the 20 districts in Shanghai was adopted for this study. The 522
      Shanghai Chinese participants were presented with a vignette describing an
      individual with depression before being asked questions designed to assess both
      their understanding of depression and their preferences surrounding professional
      help, medication, and treatment methods. A comparative approach was adopted to
      identify similarities and differences between our findings and those of two
      previous studies on the mental health literacy of Chinese living in Melbourne,
      Australia, and Hong Kong, respectively. RESULTS: A similarly low percentage of
      Chinese people in each of Shanghai, Hong Kong, and Australia recognized
      depression. Fewer Shanghai Chinese than Chinese living in Hong Kong and Australia
      ascribed the 'anxiety/stress' label to the depression vignette and endorsed
      professionals and informal network members as helpful. Although a far lower
      percentage of Shanghai Chinese endorsed the use of counseling professionals, a
      much higher percentage of the same group endorsed Chinese medical doctors and
      herbal medication. A lower percentage of Shanghai Chinese endorsed 'lifestyle
      changes' as a strategy for combating depression than did Chinese subjects living
      in Australia and Hong Kong. On the other hand, a higher percentage of Shanghai
      residents endorsed psychiatric treatment and the traditional Chinese practices of
      'eating nutritious food/taking supplements' and 'qigong' than among the other two
      groups of Chinese. CONCLUSIONS: This study underlines the need for campaigns
      aimed at improving the mental health literacy of Chinese in Shanghai. Such
      campaigns must take into consideration the socially and culturally driven beliefs
      to facilitate the development of specific education programs.

PMID- 21901402
TI  - Chemical composition and bile acid binding activity of products obtained from
      amaranth (Amaranthus cruentus) seeds.
AB  - Cardiovascular diseases are currently the greatest cause of mortality in the
      world, and dislipidemia is appearing as one of the most important risk factors.
      The binding of bile acids (BAs) has been hypothesized as a possible mechanism by
      which dietary fibers lower blood cholesterol levels. Besides the fibers, other
      components in the amaranth seeds may be related to this hypocholesterolemic
      effect. The objective of the present study was to evaluate the BA binding
      capacity of some products obtained from defatted amaranth flour (DAF) and from
      the amaranth protein concentrate (APC). The alkaline residue, rich in fibers
      (8.6%), presented the lowest binding activity for the BAs tested, with the
      exception of glycocholic acid. The DAF showed intermediary binding activity for
      all the BAs tested, although similar to that of the APC for deoxycholic acid, and
      to that of the amaranth protein hydrolysate (APH) for taurocholic acid. The DAF
      and APC showed binding activity for secondary bile acids toxic to the intestinal
      mucus. From the results, amaranth products were shown to have the ability to bind
      BAs, but it was not possible to affirm whether the main component responsible for
      this activity was the proteins, fibers or eventually some other non-evaluated
      component.

PMID- 21901403
TI  - A phase I dose escalation study of Nimotuzumab in combination with concurrent
      chemoradiation for patients with locally advanced squamous cell carcinoma of
      esophagus.
AB  - Nimotuzumab (h-R3) is a humanized anti-epidermal growth factor receptor
      monoclonal antibody. We conducted a phase I study to assess the safety,
      tolerance, maximal tolerance dose (MTD) and efficacy of h-R3 in combination with
      concurrent chemoradiation in patient with locally advanced esophageal carcinoma.
      Patients with locally advanced squamous cell carcinoma of esophagus were
      eligible. A total dose of 61.2 Gy was delivered by conventional fractionation.
      Chemotherapy was concurrently administered with irradiation every 4 weeks with PF
      regimen (cis-platinum of 25 mg/m(2)/d, d1-3; 5-Fu of 1,800 mg/m(2), intravenously
      infusion in 72 h) for 4 cycles. h-R3 was administrated weekly during irradiation
      for 6 weeks. h-R3 dose escalation started with 100 mg/week, and followed by 200
      mg/week and 400 mg/week. Three patients were enrolled in of each dose cohort. 11
      patients were enrolled in the trial with 3, 4 and 4 in 100 mg/week, 200 mg/week
      and 400 mg/week cohort, respectively. 2 patients in 200 mg/week and 400 mg/week
      cohort were withdrawn due to patients' own decisions. No dose limiting toxicity
      was observed. Grade 3-4 of esophagitis, Grade 3 of leucocytopenia and
      neutrocytopenia occurred in 18% (2/11), 18% (2/11) and 9% (1/11) of patients,
      respectively. For nimotuzumab-related toxicity only one patient experienced Grade
      1 skin rash, and no Grade >= 3 of toxicity was noticed. In 9 patients, who
      completed planned treatments, 6-month and 1-year overall survival were 78% and
      67%, respectively, and 1 year local progression-free survival, 100%. h-R3 of 400
      mg/week administered concurrently with chemoradiation was well-tolerant. MTD has
      not been reached yet.

PMID- 21901405
TI  - Physisporinus vitreus: a versatile white rot fungus for engineering value-added
      wood products.
AB  - The credo of every scientist working in the field of applied science is to
      transfer knowledge "from science to market," a process that combines (1) science
      (fundamental discoveries and basic research) with (2) technology development
      (performance assessment and optimization) and (3) technology transfer (industrial
      application). Over the past 7 years, we have intensively investigated the
      potential of the white rot fungus, Physisporinus vitreus, for engineering value
      added wood products. Because of its exceptional wood degradation pattern, i.e.,
      selective lignification without significant wood strength losses and a
      preferential degradation of bordered pit membranes, it is possible to use this
      fungus under controlled conditions to improve the acoustic properties of tonewood
      (i.e., "mycowood") as well as to enhance the uptake of preservatives and wood
      modification substances in refractory wood species (e.g., Norway spruce), a
      process known as "bioincising." This minireview summarizes the research that we
      have performed with P. vitreus and critically discusses the challenges
      encountered during the development of two distinct processes for engineering
      value-added wood products. Finally, we peep into the future potential of the
      bioincising and mycowood processes for additional applications in the forest and
      wood industry.

PMID- 21901406
TI  - [Acetylsalicylic acid for primary cardiovascular prevention dependent on the role
      of the ankle brachial index].

PMID- 21901407
TI  - [Gestational diabetes].
AB  - Gestational diabetes is one of the most common complications during pregnancy.
      Its incidence has increased in recent decades. This is partly due to improved
      screening strategies and more stringent diagnostic criteria. Using the updated
      diagnostic thresholds, it is expected that 5-10% at least of all pregnant women
      will be diagnosed with diabetes mellitus. The rationale for the novel blood
      glucose criteria are data from prospective studies reporting an increase of fetal
      and maternal complications even when the blood glucose is only slightly
      increased. For the first time, solid evidence now exists for the diagnosis and
      treatment of gestational diabetes.

PMID- 21901404
TI  - Increasing recombinant protein production in Escherichia coli through metabolic
      and genetic engineering.
AB  - Different hosts have been used for recombinant protein production, ranging from
      simple bacteria, such as Escherichia coli and Bacillus subtilis, to more advanced
      eukaryotes as Saccharomyces cerevisiae and Pichia pastoris, to very complex
      insect and animal cells. All have their advantages and drawbacks and not one
      seems to be the perfect host for all purposes. In this review we compare the
      characteristics of all hosts used in commercial applications of recombinant
      protein production, both in the area of biopharmaceuticals and industrial
      enzymes. Although the bacterium E. coli remains a very often used organism,
      several drawbacks limit its possibility to be the first-choice host. Furthermore,
      we show what E. coli strains are typically used in high cell density cultivations
      and compare their genetic and physiological differences. In addition, we
      summarize the research efforts that have been done to improve yields of
      heterologous protein in E. coli, to reduce acetate formation, to secrete the
      recombinant protein into the periplasm or extracellular milieu, and to perform
      post-translational modifications. We conclude that great progress has been made
      in the incorporation of eukaryotic features into E. coli, which might allow the
      bacterium to regain its first-choice status, on the condition that these research
      efforts continue to gain momentum.

PMID- 21901408
TI  - 1H, 13C, and 15N NMR resonance assignments of reduced full length and shortened
      forms of the Grx domain of Mus musculus TGR.
AB  - Two forms of the glutaredoxin (Grx) domain (full length Grx domain and short Grx
      lacking the N-terminal region) of Mus musculus thioredoxin glutathione reductase
      (TGR) were isotopically labelled with (15)N and (13)C isotopes, expressed and
      purified to homogeneity. We report here the (1)H, (13)C and (15)N NMR assignment
      for both Grx forms of this mouse TGR. This investigation represents the first NMR
      analysis of a mammalian TGR.

PMID- 21901409
TI  - Combination of docking, molecular dynamics and quantum mechanical calculations
      for metabolism prediction of 3,4-methylenedioxybenzoyl-2-thienylhydrazone.
AB  - In modern drug discovery process, ADME/Tox properties should be determined as
      early as possible in the test cascade to allow a timely assessment of their
      property profiles. To help medicinal chemists in designing new compounds with
      improved pharmacokinetics, the knowledge of the soft spot position or the site of
      metabolism (SOM) is needed. In silico methods based on docking, molecular
      dynamics and quantum chemical calculations can bring us closer to understand drug
      metabolism and predict drug-drug interactions. We report herein on a combined
      methodology to explore the site of metabolism prediction of a new cardioactive
      drug prototype, LASSBio-294 (1), using MetaPrint2D to predict the most likely
      metabolites, combined with structure-based tools using docking, molecular
      dynamics and quantum mechanical calculations to predict the binding of the
      substrate to CYP2C9 enzyme, to estimate the binding free energy and to study the
      energy profiles for the oxidation of (1). Additionally, the computational study
      was correlated with a metabolic fingerprint profiling using LC-MS analysis. The
      results obtained using the computational methods gave valuable information about
      the probable metabolites of (1) (qualitatively) and also about the important
      interactions of this lead compound with the amino acid residues of the active
      site of CYP2C9. Moreover, using a combination of different levels of theory sheds
      light on the understanding of (1) metabolism by CYP2C9 and its mechanisms. The
      metabolic fingerprint profiling of (1) has shown that the metabolites founded in
      highest concentration in different species were metabolites M1, M2 and M3,
      whereas M8 was found to be a minor metabolite. Therefore, our computational study
      allowed a qualitative prediction for the metabolism of (1). The approach
      presented here has afforded new opportunities to improve metabolite
      identification strategies, mediated by not only CYP2C9 but also other CYP450
      family enzymes.

PMID- 21901410
TI  - Has the role of exchange nailing in femoral nonunion diminished?

PMID- 21901412
TI  - What contributes to patient and parent satisfaction with medication in the
      treatment of children with ADHD? A report on the development of a new rating
      scale.
AB  - Satisfaction with medication is important in the evaluation of overall treatment
      outcome. There is a lack of consistent and validated rating scales for
      satisfaction with medication in ADHD, therefore comparison across studies is
      difficult. Here, we analyse the psychometric properties of the satisfaction with
      medication scale (SAMS), a new item-based questionnaire that assesses
      satisfaction with ADHD medication. Furthermore, we evaluate the predictive effect
      of ADHD symptoms and quality of life (QoL) on satisfaction. Data on satisfaction
      with Equasym XL((r)) (methylphenidate) were collected in the OBSEER study using
      the parent (SAMS-P, n = 589) and patient (SAMS-S, n = 552) versions of the SAMS
      questionnaire. Internal consistency, item-total and cross-informant correlations,
      and the stability of satisfaction ratings over time were assessed. Satisfaction
      with medication scores were then correlated with ratings of ADHD symptoms and
      QoL. Rates of overall satisfaction with Equasym XL((r)) among parents and
      children were high (>70%), as was internal consistency for both SAMS-P and SAMS-S
      (Cronbach's alpha > 0.9). Similarly, item-total correlations were high (r = 0.71
      0.90) for SAMS-P and medium-high (r = 0.57-0.77) for SAMS-S. Cross-informant
      correlations and the stability of satisfaction ratings were moderate (r = 0.54
      0.59 and 0.48-0.60, respectively). ADHD symptom and QoL ratings were
      significantly negative and positive predictors of satisfaction, explaining 36-52%
      of satisfaction variance at the final visit. The results show that parent and
      patient satisfaction was high and could be assessed reliably with the new SAMS
      questionnaire. Parent and patient ratings were moderately correlated, and symptom
      severity, functional impairment and QoL were the most significant predictors of
      satisfaction.

PMID- 21901411
TI  - A posterior versus anterior surgical approach in combination with debridement,
      interbody autografting and instrumentation for thoracic and lumbar tuberculosis.
AB  - PURPOSE: The purpose of this study was to compare posterior and anterior surgical
      approach in combination with debridement, interbody autografting and
      instrumentation for thoracic and lumbar tuberculosis. These approaches were
      compared in terms of the operation duration, intraoperative blood loss, bony
      fusion, intraoperative and postoperative complications, neurological status and
      the angle of kyphosis. METHODS: Forty-seven patients with thoracic and lumbar
      tuberculosis who underwent either the posterior or the anterior approach in
      combination with debridement, interbody autografting and instrumentation from
      January 2004 to March 2010 were reviewed retrospectively. In group A (n = 25),
      the posterior approach was combined with debridement, interbody autografting and
      instrumentation. In group B (n = 22), the anterior approach was performed in
      addition to debridement, interbody autografting and instrumentation. RESULTS: All
      cases were followed up for 12-62 months. There was no statistically significant
      difference between groups in terms of the operation duration, intraoperative
      blood loss, bony fusion, intraoperative and postoperative complications,
      neurological status and the angle of kyphosis (p > 0.05). Good clinical outcomes
      were achieved in both groups. CONCLUSIONS: The posterior approach combined with
      debridement, interbody autografting and instrumentation is an alternative
      procedure to treat thoracic and lumbar tuberculosis. The posterior approach is
      sufficient for lesion debridement. In addition, the posterior approach can
      maintain spinal stabilisation and prevent loss of corrected vertebral alignment
      as effectively as the anterior approach.

PMID- 21901413
TI  - Assessment of daily profiles of ADHD and ODD symptoms, and symptomatology related
      to ADHD medication, by parent and teacher ratings.
AB  - DAYAS is a new two-part rating scale that assesses: (1) ADHD and ODD symptoms
      (externalising symptom ratings) and (2) symptomatology potentially related to
      ADHD medication (potentially medication-related symptoms) in real-world settings
      at different time periods throughout a normal school day. Data from a proof-of
      concept study and two observational trials (Medikinet((r)) retard
      [methylphenidate] and the Equasym XL((r)) [methylphenidate] OBSEER study)
      evaluated: (1) validity of weekly externalising symptom ratings using DAYAS, in
      place of daily ratings; (2) reliability and internal consistency of DAYAS ratings
      for externalising symptoms and potentially medication-related symptoms; and (3)
      convergent and divergent validity of the externalising symptom ratings with
      existing validated scales. From the proof-of-concept study, daily scores by
      period of day and during the whole day correlated strongly with equivalent weekly
      scores (r = 0.83-0.92). Internal consistency of externalising symptom rating
      scales calculated from pooled data were acceptable or good by period of day
      (Cronbach's alpha = 0.68-0.90) and very high for whole day scores (Cronbach's
      alpha = 0.88-0.95). Internal consistency of the rating scale for potentially
      medication-related symptoms was also good for both teacher and parent ratings.
      From OBSEER data, correlations between FBB-ADHD total symptom scores and ratings
      on both parent and teacher versions of DAYAS were high (r = 0.73 and r = 0.84,
      respectively). Correlations between DAYAS and SDQ were highest for the SDQ
      subscales hyperactivity and conduct problems and substantially lower for pro
      social behaviour, peers and emotional problems. The DAYAS rating scale had good
      internal consistency, and DAYAS scores correlated well with existing validated
      scales and the SDQ subscales hyperactivity and conduct problems. Weekly DAYAS
      scores (whole day and by period of day) could be considered a suitable
      replacement for daily assessment scores.

PMID- 21901414
TI  - An observational study of once-daily modified-release methylphenidate in ADHD:
      the effect of previous treatment on ADHD symptoms, other externalising symptoms
      and quality-of-life outcomes.
AB  - Methylphenidate (MPH) is the most commonly prescribed stimulant for children with
      ADHD. Data on the effects of different MPH formulations in real-life settings are
      scarce, and the role of previous therapy on treatment outcome when switching
      medications has not been well studied. OBSEER was an observational study designed
      to evaluate the effectiveness and safety of Equasym XL((r)) in routine care. This
      study assessed whether the improvements reported with Equasym XL((r)) are
      influenced by the degree of symptom control achieved with the previous
      medication. Patients enrolled in OBSEER were stratified by prior treatment (none,
      MPH-immediate release [IR] once daily [o.d.] [MPH-IR o.d.], MPH-IR repeated [MPH
      IR >o.d.] and MPH-MR [modified release] excluding Equasym XL((r))), and changes
      in ADHD and other externalising symptoms (CGI-S, FBB-ADHD and DAYAS) and quality
      of life (QoL, KINDL) were evaluated during treatment with Equasym XL((r)). A
      total of 782 patients were analysed. Significant group-by-time interactions were
      found for all symptom variables analysed, indicating that effects varied by
      previous medication. For CGI-S and FBB-ADHD total scores, the greatest reductions
      in ADHD symptoms were observed in the treatment-naive subgroup, followed (in
      order) by MPH-IR o.d., MPH-IR >o.d. and MPH-MR. A similar profile was seen for
      DAYAS ratings for all periods of the day except the evening, when there were no
      significant differences between subgroups. Similarly, the treatment-naive and MPH
      IR o.d. subgroups showed the greatest improvements in KINDL ratings. Although
      effects were greatest for treatment-naive patients, improvements were also
      observed in the prior treatment subgroups for symptoms and QoL. This suggests
      that a change to Equasym XL((r)) may be beneficial in patients with suboptimal
      effects on prior medication.

PMID- 21901415
TI  - Relationship between quality of life and psychopathological profile: data from an
      observational study in children with ADHD.
AB  - Although ADHD significantly affects the quality of life (QoL) of patients and
      their families, QoL in children with ADHD has rarely been investigated in
      association with psychopathological profile, and the relationship remains
      unclear. The open-label OBSEER study evaluated the effectiveness and tolerability
      of Equasym XL((r)), a modified-release methylphenidate, in routine care of
      children and adolescents (aged 6-17 years) with ADHD. At baseline, questionnaires
      assessing psychopathological profile (Strengths and Difficulties Questionnaire,
      SDQ; parental ratings) and QoL (KINDL; parent, child or adolescent versions) were
      completed; QoL was reassessed at final visit. We analysed the relationship
      between psychopathology and parent/patient-rated QoL in ADHD at baseline. Data
      from 721 consecutively referred children and adolescents were analysed. QoL was
      similarly low from parent and self-ratings and independent of severity on the SDQ
      subscale hyperactivity/inattention. Self-ratings indicated that additional
      conduct disorder was associated with further reduction in QoL. Similarly,
      children with high scores from parent and adolescent ratings on the SDQ subscale
      conduct problems had reduced QoL on some KINDL subscales. Adolescents with ADHD
      not receiving medication at baseline reported lower QoL than those already on
      medication. Results show that children and adolescents with ADHD have low QoL,
      independent of core symptom severity. Additional conduct problems may further
      impact QoL negatively, while ADHD medication use may show a trend towards
      improved QoL. Not all psychopathological problems associated with ADHD affect QoL
      similarly. As parents appear to have a less critical view of QoL compared with
      children's self-ratings, both parent and child ratings should be included in
      clinical assessments.

PMID- 21901416
TI  - An observational study of once-daily modified-release methylphenidate in ADHD:
      quality of life, satisfaction with treatment and adherence.
AB  - Attention deficit hyperactivity disorder (ADHD) impacts significantly on the
      quality of life (QoL) of patients and their families. Choice of therapy is
      increasingly influenced by treatment satisfaction and patient preference, with
      once-daily modified-release methylphenidate (MPH-MR) formulations offering clear
      benefits compared with immediate-release (IR) dosage forms. The effects of MPH-MR
      on QoL in ADHD have not been widely investigated and need more clarity in
      practice. The open-label OBSEER study evaluated the effectiveness and
      tolerability of Equasym XL((r)), a MPH-MR formulation, in routine practice.
      Children and adolescents (aged 6-17 years) with ADHD and attending school were
      included if Equasym XL((r)) treatment was planned by the treating physician.
      Physicians, parents and patients completed questionnaires assessing QoL (KINDL;
      parent, child or adolescent versions), satisfaction with medication, adherence
      and treatment tolerability at baseline (Visit 1), 1-3 weeks (Visit 2) and 6-12
      weeks (Visit 3) over a maximum 3-month observation period. Data from 822
      consecutively referred patients were analysed. QoL and medication satisfaction
      increased from Visit 1 to Visit 3, with both patients and parents rating therapy
      with Equasym XL((r)) as better than previous drug therapy. KINDL total score
      effect sizes were 0.67 (parents' ratings), 0.52 (children's ratings) and 0.51
      (adolescents' ratings; all p < 0.001). All KINDL subscores also increased: both
      parents and patients had the greatest improvement for school. Adherence to
      Equasym XL((r)) was frequently rated as superior to prior treatment, particularly
      compared with MPH-IR repeated dosing. Treatment was generally well tolerated;
      approximately 3% of the patients discontinued treatment due to adverse events.
      Equasym XL((r)) improved QoL compared with prior therapy, and resulted in good
      medication satisfaction and adherence in drug-naive and previously treated
      patients.

PMID- 21901417
TI  - An observational study of once-daily modified-release methylphenidate in ADHD:
      effectiveness on symptoms and impairment, and safety.
AB  - ADHD affects over 5% of children worldwide. It is typically treated with
      stimulant medications, and methylphenidate (MPH) is the most commonly prescribed.
      This study investigated the effectiveness, on symptoms and impairment, and safety
      of Equasym XL((r)), a combination of 30% immediate-release and 70% modified
      release MPH, in the treatment of ADHD in daily clinical practice. This open
      label, observational, post-marketing surveillance study was conducted in 169
      centres in Germany. Eligible patients, aged 6-17 years, were diagnosed with ADHD
      and about to begin treatment with Equasym XL((r)). Effectiveness was assessed by
      physicians using the clinical global impression (CGI) severity and improvement
      scales; teachers and parents completed questionnaires evaluating ADHD symptoms
      and behavioural problems (DAYAS, FBB-ADHD and SDQ-P). Assessments were carried
      out at baseline, after 1-3 and 6-12 weeks of treatment. Of 852 enrolled patients,
      822 were evaluable; 25.30% were treatment naive, 69.84% had previously received
      different MPH formulations, and 4.87% had received other medications. ADHD
      symptoms improved from baseline to last visit for the majority of patients for
      all outcome measures. According to physician ratings of core ADHD symptoms,
      75.73% of patients showed improvements on the CGI-Improvement scale, 17.77% had
      no change, and 6.50% worsened. In teacher and parent ratings, the effectiveness
      of Equasym XL((r)) was rated better than prior therapy at all measured time
      points across the day, particularly late morning (teachers) and early afternoon
      (parents). Equasym XL((r)) was generally well tolerated; only 3.16% of patients
      permanently discontinued treatment due to adverse events. Equasym XL((r)) is
      effective and well tolerated in daily clinical practice.

PMID- 21901418
TI  - Editorial: Observational studies in ADHD: the effects of switching to modified
      release methylphenidate preparations on clinical outcomes and adherence.
AB  - Patients with ADHD may have better adherence to treatment with modified-release
      methylphenidate (MPH-MR) formulations, which are taken once daily, compared with
      immediate-release (IR) formulations, which need to be taken several times a day.
      Data on long-term outcomes such as adherence may be lacking from randomised
      controlled trials as these are usually only short-term. Observational studies, if
      performed and reported appropriately, can provide valuable long-term data on such
      outcomes, as well as additional information on effectiveness and efficiency, from
      a real-life setting. By reviewing previous observational studies that have
      investigated switching treatment from MPH-IR to MPH-MR, results from a new,
      naturalistic observational study, the OBSEER study, are put into context. We
      conclude that, based on observational trial data, switching from MPH-IR to MPH-MR
      is a valid clinical approach, with the potential for improved clinical outcome
      and treatment adherence.

PMID- 21901419
TI  - Glucagon like-peptide-1 receptor is covalently modified by endogenous mono-ADP
      ribosyltransferase.
AB  - Our previous study revealed a mono-ADP-ribosyltransferase mediated in vitro mono
      ADP-ribosylation of IC(3) peptide, a peptide with sequence corresponded to third
      intracellular loop of glucagon like-peptide-1 (GLP-1) receptor. Furthermore,
      Arg(348) was shown to be modified amino acid residue although its mutation did
      not eliminate mono-ADP-ribosylation completely. In order to further study the
      signaling mechanisms of GLP-1 receptor, we took on lease a possibility that an
      alternative site of enzymatic modification exist so mono-ADP-ribosylation of
      Cys(341) was hypothesized. The results confirmed both Arg(348) and Cys(341) as a
      site of mono-ADP-ribosylation where Arg(348) is modified predominantly. Sum of
      mono-ADP-ribosylation rate of both single IC(3) mutants coincided with IC(3)
      rate. What is in vivo role of Cys(341) mono-ADP-ribosylation is entirely
      speculative but our study represents an important step toward a complete
      understanding of signaling via GLP-1 receptor.

PMID- 21901420
TI  - HSG1, a grape Bcl-2-associated athanogene, promotes floral transition by
      activating CONSTANS expression in transgenic Arabidopsis plant.
AB  - HSG1 (Heat shock-induced gene 1) is one of the high-temperature-induced proteins
      in grapevine. Sequence analysis has demonstrated that HSG1 is a grape Bcl-2
      associated athanogene (BAG) that contains IQ and BAG domains in its sequence.
      HSG1 expression was not detected in leaves without heat treatment, while
      tendrils, stems, flowers, and berries expressed HSG1 even without heat treatment.
      By heat treatment at 45 degrees C for 60 min, HSG1 expression was upregulated in
      both leaves and berries. HSG1-overexpressing Arabidopsis plant remained viable
      even after exposure to extremely high temperatures. Although no morphological
      changes were observed, the HSG1-overexpressing Arabidopsis plant exhibited faster
      floral transition than the control plant. Analysis of the transcription profile
      of HSG1-overexpressing seedling by cDNA microarray and quantitative RT-PCR
      demonstrated that the gene expression of the flowering promoter, CONSTANS (CO),
      in the photoperiod pathway was up-regulated in the seedling. Importantly, the
      overexpression of HSG1 increased CO expression by ~400% compared with the control
      seedling. Meanwhile, heat treatment upregulated grape CO expression in grape
      leaves. Our study provides the possibility that plant BAG protein may be related
      to the regulation of floral transition by activating CO expression in the
      photoperiod pathway.

PMID- 21901421
TI  - The LOX-1 3'UTR188CT polymorphism and coronary artery disease in Turkish
      patients.
AB  - In coronary artery disease (CAD), a potentially reversible factor leading to
      cardiac death is left ventricular hypertrophy (LVH). The 3'untranslated region
      (3'UTR) 188CT polymorphism of lectin-like oxidized low-density lipoproteins
      receptor-1 (LOX-1) gene has been associated with an increased risk for CAD. We
      aim to investigate, in a Turkish population, whether 3'UTR188CT variation could
      affect the development of LVH in CAD patients. In a population-based case-control
      study, we compared 83 cases with CAD and 99 healthy controls for this
      polymorphism. The LOX-1 3'UTR188CT genotypes were determined by PCR-RFLP
      technique. LOX-1 3'UTR188 TT genotype was associated with significantly increased
      systolic blood pressure (P = 0.047) and risk of LVH (P = 0.014, OR: 3.541) when
      compared with the C allele carriers. In addition, the TT genotype was positively
      associated with decreased levels of HDL-cholesterol in the control subjects (P =
      0.031) and increased levels of VLDL-C in the patient group (P = 0.009). The LOX-1
      3'UTR188CT gene polymorphism may predispose to the development of LVH in CAD
      patients, dependent on blood pressure.

PMID- 21901422
TI  - Muscle transcriptomic analyses in Angus cattle with divergent tenderness.
AB  - Beef tenderness contributes significantly to variation of beef palatability, and
      is largely influenced by various genetic and environmental factors. To identify
      candidate genes and pathways related to beef tenderness, we analyzed the
      longissimus dorsi (LD) muscle of Angus cattle that had different degrees of
      tenderness, measured by Warner-Bratzler shear force (WBSF). Microarray and RT-PCR
      analyses identified 53 genes that were differentially expressed in LD samples
      categorized as either tough or tender, including myosin, heavy chain 3 skeletal
      muscle embryonic (MYH3), myosin heavy chain 8 skeletal muscle perinatal (MYH8),
      guanylate binding protein 5 (GBP5), fatty acid binding protein 4 (FABP4),
      Stearoyl-coenzyme A desaturase (SCD), Fatty acid synthase (FASN), ubiquitin-like
      with PHD and ring finger domains 1 (UHRF1). Most of these genes are involved in
      lipid metabolism and skeletal muscle contraction. Employing Gene ontology (GO)
      and Ingenuity Pathway Analysis (IPA), several GO terms and pathways were found to
      be related to hydrolase, peptidase and GTPase activity, lipid metabolism, small
      molecule biochemistry, molecular transport, and tissue development. Overall, this
      analysis provides insight into the metabolic relationships between muscle biology
      and beef quality.

PMID- 21901423
TI  - Organised assistance to suicide in England?
AB  - Guidelines provided by the Director of Public Prosecutions suggest that anyone
      assisting another to commit suicide in England and Wales, or elsewhere, will not
      be prosecuted provided there are no self-seeking motives and no active
      encouragement. This reflects the position in Switzerland. There, however, no
      difference is made between assistance and inducement. In addition, the Swiss
      approach makes it possible to establish organisations to assist the suicides of
      both their citizens and foreign visitors. It should not be assumed that this
      approach is without controversy in Switzerland. Proposals for reform continue to
      be debated there, not least because of the concern about some of the actual
      practices of certain end-of-life organisations. It is likely that a few English
      citizens will continue to avail themselves of these services in Switzerland if
      they cannot find the help they require here. This paper explores the legitimacy
      of the current restrictive position adopted towards assisted suicide in England.
      It argues that the provisions within the guidelines prohibiting organisations
      that assist suicides, leaves some without the help they need. While legislative
      decriminalisation of assisted suicide and the establishment of state-sponsored
      suicide centres would represent the most permissive regime, this paper proposes
      that this would be a step too far. The preference here is for decriminalisation
      but adopting a 'middle way' between the two extremes: the more permissive
      approach provided by the 'Swiss model' is one that could be employed here, albeit
      within a more robust regulatory regime.

PMID- 21901424
TI  - Amyloid pathway-based candidate gene analysis of [(11)C]PiB-PET in the
      Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort.
AB  - Amyloid imaging with [(11)C]Pittsburgh Compound-B (PiB) provides in vivo data on
      plaque deposition in those with, or at risk for, Alzheimer's disease (AD). We
      performed a gene-based association analysis of 15 quality-controlled amyloid
      pathway associated candidate genes in 103 Alzheimer's Disease Neuroimaging
      Initiative participants. The mean normalized PiB uptake value across four brain
      regions known to have amyloid deposition in AD was used as a quantitative
      phenotype. The minor allele of an intronic SNP within DHCR24 was identified and
      associated with a lower average PiB uptake. Further investigation at whole-brain
      voxel-wise level indicated that non-carriers of the minor allele had higher PiB
      uptake in frontal regions compared to carriers. DHCR24 has been previously shown
      to confer resistance against beta-amyloid and oxidative stress-induced apoptosis,
      thus our findings support a neuroprotective role. Pathway-based genetic analysis
      of targeted molecular imaging phenotypes appears promising to help elucidate
      disease pathophysiology and identify potential therapeutic targets.

PMID- 21901425
TI  - Toward dysfunctional connectivity: a review of neuroimaging findings in pediatric
      major depressive disorder.
AB  - Child and adolescent psychiatric neuroimaging research typically lags behind
      similar advances in adult disorders. While the pediatric depression imaging
      literature is less developed, a recent surge in interest has created the need for
      a synthetic review of this work. Major findings from pediatric volumetric and
      functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy
      (MRS), diffusion tensor imaging (DTI) and resting state functional connectivity
      studies converge to implicate a corticolimbic network of key areas that work
      together to mediate the task of emotion regulation. Imaging the brain of children
      and adolescents with unipolar depression began with volumetric studies of
      isolated brain regions that served to identify key prefrontal, cingulate and
      limbic nodes of depression-related circuitry elucidated from more recent advances
      in DTI and functional connectivity imaging. Systematic review of these studies
      preliminarily suggests developmental differences between findings in youth and
      adults, including prodromal neurobiological features, along with some continuity
      across development.

PMID- 21901426
TI  - Microarchitectural changes in the aging skeleton.
AB  - The age-related reduction in bone mass is disproportionally related to skeletal
      weakening, suggesting that microarchitectural changes are also important
      determinants of bone quality. The study of cortical and trabecular
      microstructure, which for many years was mainly based on two-dimensional
      histologic and scanning electron microscopy imaging, gained a tremendous momentum
      in the last decade and a half, due to the introduction of microcomputed
      tomography (MUCT). This technology provides highly accurate qualitative and
      quantitative analyses based on three-dimensional images at micrometer resolution,
      which combined with finite elemental analysis predicts the biomechanical
      implications of microstructural changes. Global MUCT analyses of trabecular bone
      have repeatedly suggested that the main age-related change in this compartment is
      a decrease in trabecular number with unaltered, or even increased, trabecular
      thickness. However, we show here that this may result from a bias whereby thick
      trabeculae near the cortex and the early clearance of thin struts mask authentic
      trabecular thinning. The main cortical age-related change is increased porosity
      due to negatively balanced osteonal remodeling and expansion of Haversian canals,
      which occasionally merge with endosteal and periosteal resorption bays, thus
      leading to rapid cortical thinning and cortical weakening. The recent emergence
      of CT systems with submicrometer resolution provides novel information on the age
      related decrease in osteocyte lacunar density and related micropetrosis, the
      result of lacunar hypermineralization. Last but not least, the use of the
      submicrometer CT systems confirmed the occurrence of microcracks in the skeletal
      mineralized matrix and vastly advanced their morphologic characterization and
      mode of initiation and propagation.

PMID- 21901427
TI  - Vitamin D in the Persian Gulf: integrative physiology and socioeconomic factors.
AB  - Countries of the Persian Gulf region--Bahrain, Iran, Iraq, Kuwait, Oman, Qatar,
      Saudi Arabia, and United Arab Emirates--have become increasingly modernized,
      resulting in a transformation of lifestyle based on technology, sedentary
      activity, lack of sunlight, and unhealthy dietary patterns. These factors have
      led to a higher prevalence not only of vitamin D undernutrition, but also chronic
      obesity, insulin resistance, prediabetes, and type 2 diabetes. This review
      explores the integrative physiologic effects of vitamin D with socioeconomic
      factors and propose a hypothesis-driven model for their contributions to obesity
      and diabetes in the Persian Gulf. Further research into these interactions may
      ultimately lead to novel preventive strategies and therapies for metabolic
      disorders in this geographic region.

PMID- 21901429
TI  - Moderation of the association between media exposure and youth smoking onset:
      race/ethnicity, and parent smoking.
AB  - This study of youth smoking onset aims to replicate previously published media
      moderation effects for race/ethnicity in a national longitudinal multiethnic
      sample of U.S. adolescents. Previous research has demonstrated that associations
      between media and smoking during adolescence are greater for Whites than
      Hispanics or Blacks, and for youth living in non-smoking families. In this study,
      changes in smoking status over 24 months were assessed among 4,511 baseline never
      smokers. The incidence of smoking onset was 14.3% by 24 months with no
      differences by race/ethnicity. Blacks had higher exposure to movie smoking and
      overall television viewing compared with Whites and Hispanics. Whites responded
      to movie smoking regardless of parent smoking but more strongly if their parents
      were non-smokers. In contrast, Black adolescents showed little behavioral
      response to any media, regardless of parent smoking. Hispanic adolescents
      responded only to TV viewing and only when their parents did not smoke. In an
      analysis assessing the influence of the race of smoking characters on smoking
      behavior of White and Black adolescents, Whites responded to both White and Black
      movie character smoking, whereas Blacks responded only to smoking by Black movie
      characters. Taken as a whole, the findings replicate and extend previous
      findings, suggesting media factors are more influential among adolescents at low
      to moderate overall risk for smoking. We draw analogies between these low
      moderate risk adolescents and "swing voters" in national elections, suggesting
      that media effects are more apt to influence an adolescent in the middle of the
      risk spectrum, compared with his peers at either end of it.

PMID- 21901430
TI  - A critical analysis of three quantitative methods of assessment of hepatic
      steatosis in liver biopsies.
AB  - The issue of adequately quantitatively evaluating hepatic steatosis is still
      unresolved. Therefore, we compared three methods of quantitative assessment. Two
      groups of mice (n = 10 each) were fed standard chow (10% fat, SC group) or a high
      fat diet (60% fat, HF group) for 16 weeks, and hepatic triglyceride (HT) and
      liver tissue were then studied. Paraplast-embedded tissues stained by hematoxylin
      and eosin (H-E) were compared to frozen sections stained by Oil Red-O (ORO). In
      addition, the volume density of steatosis (Vv[steatosis, liver]) was measured by
      point counting (P-C, sections H-E or ORO) or by image analysis (I-A, sections
      ORO). HT was significantly higher in the HF group (104% greater, P = 0.0004) than
      in the SC group. With P-C and H-E, Vv[steatosis, liver] was 4.80 +/- 0.90% in the
      SC group and 33.50 +/- 3.17% in the HF group (600% greater, P < 0.0001). With P-C
      and ORO, Vv[steatosis, liver] was 4.86 +/- 0.89% in the SC group and 25.21 +/-
      1.27% in the HF group (420% greater, P < 0.0001). With I-A and ORO, Vv[steatosis,
      liver] was 4.17 +/- 0.85% in the SC group and 23.35 +/- 1.58% in the HF group
      (460% greater, P < 0.0001). Correlations between Vv[steatosis, liver] and HT were
      strong and significant in all methods. In conclusion, all methods were
      appropriate and reproducible. In P-C and H-E, there is a slight overestimation of
      steatosis in the HF animals in comparison to frozen sections and ORO; in frozen
      sections, differences between P-C and I-A are insignificant.

PMID- 21901432
TI  - Protective effects of curcumin against sodium fluoride-induced toxicity in rat
      kidneys.
AB  - In the present study, the protective effect of curcumin against sodium fluoride
      induced nephrotoxicity was evaluated in rats. Renal injury was induced by daily
      administration of 600 ppm sodium fluoride in drinking water for 1 week. One week
      before the administration of fluoride, the animals selected as study group were
      given curcumin (10 and 20 mg/kg body weight, intraperitoneally). After 1 week,
      lipid peroxidation level, activities of superoxide dismutase, catalase, and level
      of glutathione in kidney homogenate were measured. Blood serum samples were
      examined for creatinine, serum urea, and blood urea nitrogen levels. Another
      group of rats received vitamin C (10 mg/kg) as standard antioxidant. The results
      show that curcumin and vitamin C treatment prior to fluoride administration
      normalized the levels of serum creatinine, serum urea, and blood urea nitrogen.
      Moreover, curcumin and vitamin C administrations prevented the antioxidant enzyme
      decreasing and lipid peroxidation levels imbalance. In conclusion, curcumin
      treatment at the doses of 10 and 20 mg/kg (intraperitoneally) showed significant
      nephroprotective effects.

PMID- 21901431
TI  - Effects of diet on high-density lipoprotein cholesterol.
AB  - Multiple dietary factors have been shown to increase high-density lipoprotein
      cholesterol (HDL-C) concentrations, and HDL-C has been inversely associated with
      coronary heart disease (CHD) risk. Replacement of dietary carbohydrate with
      polyunsaturated, monounsaturated and saturated fat has been associated with
      progressively greater increases in HDL-C (7-12%) in addition to other lipid
      changes. Added sugars, but not high glycemic carbohydrates, have been associated
      with decreased HDL-C. Alcohol consumption has been associated with increased HDL
      C (9.2%) independent of changes in other measured lipids. Modest effects on HDL-C
      (~4-5%) among other lipid and non-lipid CHD risk factors have also been observed
      with weight loss by dieting, omega-3 fatty acids, and a Mediterranean diet
      pattern. The CHD benefit of increasing HDL-C is unclear given the inconsistent
      evidence from HDL-raising pharmacologic trials. Furthermore, pleiotropic effects
      of diet preclude attribution of CHD benefit specifically to HDL-C. Investigation
      into functional or other properties of HDL may lend further insight.

PMID- 21901433
TI  - Organ histopathological changes and its function damage in mice following long
      term exposure to lanthanides chloride.
AB  - Due to increasing applications of lanthanides (Ln) in industry and daily life,
      numerous studies confirmed that Ln exposure may result in organ damages in mice
      and rats, while very few studies focused on several organs damages
      simultaneously. In order to compare the toxicity of Ln on organs, mice were
      exposed to LaCl(3), CeCl(3), and NdCl(3) of a dose of 20 mg/kg body weight for
      consecutive 60 days, respectively, then histopathological changes of liver,
      kidney, and heart, and their function were investigated. The results showed that
      long-term exposure to Ln caused cell necrosis and basophilia of liver, ambiguity
      of renal tubule architecture, congestion of blood vessel and capillary of kidney,
      and heart hemorrhage. The histopathological changes of liver, kidney, and heart
      in mice caused by Ce(3+) was most severe; the effect by Nd(3+) was slighter than
      Ce(3+) but more severe than La(3+). The assay of serum biochemical parameters
      suggested that Ln exposure severely impaired the functions of liver, kidney, and
      myocardium in mice. These findings suggested that long-term exposure to Ln
      resulted in histopathological changes of liver, kidney, and heart, and their
      function damages. Therefore, we thought that long-term application of the
      products containing Ln on human should be cautious.

PMID- 21901428
TI  - Oxidative stress and beta-amyloid protein in Alzheimer's disease.
AB  - Oxidative stress has been proposed to be an important factor in the pathogenesis
      of Alzheimer's disease (AD) and contributed to beta-amyloid (Abeta) generation.
      Interaction between oxidative stress and neuro-inflammation leads to Abeta
      generation. AD is associated with an increase in blood-brain barrier (BBB)
      permeability due to tight junction involvement. Oxidative stress decreases the
      expression of low-density lipoprotein receptor-related protein 1 and up-regulates
      receptor for advanced glycation end products in BBB and increases the BBB
      permeability, which could potentially lead to increased deposition of Abeta
      within AD brain. Apoptosis takes place in the pathogenesis of AD, and oxidative
      stress contributes to apoptosis through both extrinsic pathway and intrinsic
      pathway. Oxidative stress-induced apoptosis may be a potential factor to Abeta
      generation. Abeta generation requires two sequential cleavages of APP, with the
      two proteolytic enzymes: beta-secretase and gamma-secretase. Oxidative damage up
      regulates Abeta via inducing activity of beta- and gamma-secretases. In this
      review, we will focus on the mechanism and pathway that oxidative stress
      contributes to Abeta generation.

PMID- 21901434
TI  - The effects of physical exercise on the serum iron profile in spontaneously
      hypertensive rats.
AB  - The purpose of this study was to evaluate the profile of serum iron in
      spontaneously hypertensive rats after an aerobic physical exercise. To accomplish
      this, 12 normotensive Wistar rats and 12 spontaneously hypertensive rats were
      distributed into "physical exercise" and "no physical exercise" groups. The
      animals in the physical exercise group underwent to an aerobic exercise for a
      total of 4 weeks. Blood was collected for the analysis of iron. Our results
      indicate that rats of the physical exercise group had significantly lower serum
      iron levels after the aerobic exercise protocol compared to the spontaneously
      hypertensive rats no physical exercise group (F ((3,16)) = 4.4915, p < 0.01). No
      significant difference was found between no physical exercise groups. The results
      indicated that the difference in iron may be due to an increased demand for iron,
      prompted by chronic physical exercise. In addition, erythrocytosis has been
      associated with increased blood pressure in spontaneously hypertensive rats,
      suggesting that iron reduction may be related to decreased blood pressure in
      these animals.

PMID- 21901436
TI  - The peer review process III: when the decision is made.

PMID- 21901435
TI  - Advanced maternal age as a risk factor for stress urinary incontinence: a review
      of the literature.
AB  - The pathophysiology of stress urinary incontinence (SUI) is multifactorial and
      evidence supports a critical role of pregnancy and vaginal delivery. This review
      dissects epidemiologic literature to determine the weight of evidence on the role
      of advanced maternal age (AMA) as a risk factor for the development of subsequent
      or persistent SUI. We conducted a Medline search using the keywords postpartum,
      SUI, maternal age, pregnancy, and incontinence. The published literature was
      critically analyzed. Evidence supports that childbirth trauma contributes to the
      development and severity of SUI. Yet, there is contradicting evidence as to
      whether AMA increases the risk. AMA clearly represents an independent risk factor
      for postpartum SUI. However, long-term studies did not confirm this observation.
      Whether this finding is suggestive of a true biologic signal that is lost with
      competing risk factors over time warrants further research.

PMID- 21901437
TI  - The peer review process II: to review and be reviewed.

PMID- 21901438
TI  - The peer review process I: submitting a manuscript.

PMID- 21901439
TI  - Skene's gland revisited: function, dysfunction and the G spot.

PMID- 21901440
TI  - A state agency-university partnership for translational research and the
      dissemination of evidence-based prevention and intervention.
AB  - This article describes a decade-long partnership between the Prevention Research
      Center at Penn State and the Pennsylvania Commission on Crime and Delinquency.
      This partnership has evolved into a multi-agency initiative supporting the
      implementation of nearly 200 replications of evidence-based prevention and
      intervention programs, and a series of studies indicating a significant and
      sustained impact on youth outcomes and more efficient utilization of system
      resources. We describe how the collaboration has developed into a sophisticated
      prevention support infrastructure, discuss the partnership and policy lessons
      learned throughout this journey, and identify remaining issues in promoting this
      type of research-policy partnership.

PMID- 21901441
TI  - The IL-10 promoter polymorphism at position -592 is correlated with
      susceptibility to occult HBV infection.
AB  - Occult hepatitis B infection (OBI) is characterized as a form of hepatitis in
      which detectable amounts of HBV-DNA can be monitored in the peripheral blood of
      patients whereas the hepatitis B surface antigen is undetectable. The main aim of
      this study was to investigate whether there is a relationship between OBI and
      single nucleotide polymorphisms in the -592 region of the IL-10 gene. In this
      study, the polymorphism at position -592 of the IL-10 promoter of 57 OBI cases
      was compared and correlated to that of 100 healthy controls by PCR-RFLP
      techniques. Our results showed that patient and control groups had significant
      differences regarding genotypes and alleles of the -592 polymorphism in the IL-10
      gene. Based on our results, it can be concluded that the -592 polymorphism within
      the promoter of the IL-10 gene is associated with OBI.

PMID- 21901442
TI  - The role of cysteine conjugation in the detoxification of microcystin-LR in liver
      of bighead carp (Aristichthys nobilis): a field and laboratory study.
AB  - The role of glutathione (GSH) and cysteine (Cys) conjugates in the detoxification
      of microcystin-LR (MC-LR) in bighead carp (Aristichthys nobilis) was examined
      under laboratory and field conditions. Wild individuals of bighead carp were
      collected from 5 eutrophic lakes along the Yangtze River, while in laboratory
      experiment, bighead carp were injected intraperitoneally with 500 MUg purified MC
      LR/kg body weight (bw). Contents of MC-LR and its glutathione (MC-LR-GSH) and
      cysteine conjugates (MC-LR-Cys) in the liver of bighead carp were determined by
      liquid chromatography electrospray ionization mass spectrum (LC-ESI-MS). In
      laboratory experiment, low concentrations of MC-LR-GSH (mean: 0.042 MUg/g dry
      weight (DW)) were always detectable, and the mean ratio of MC-LR-Cys to MC-LR-GSH
      was 6.55. While, in field study, relatively high MC-LR-Cys concentration (mean:
      0.22 MUg/g DW) was detected, whereas MC-LR-GSH was occasionally detectable, and
      the average ratio of MC-LR-Cys to MC-LR-GSH was as high as 71.49. A positive
      correlation was found between MC-LR-Cys concentration in the liver of bighead
      carp and MC-LR content in seston from the five lakes (r = 0.85). These results
      suggest that MC-LR-Cys might be much more important than MC-LR-GSH in the
      detoxification of MC-LR in fish liver, and that cysteine conjugation of MC-LR
      might be a physiological mechanism for the phytoplanktivorous bighead carp to
      counteract toxic cyanobacteria.

PMID- 21901443
TI  - MercNet: a national monitoring network to assess responses to changing mercury
      emissions in the United States.
AB  - A partnership of federal and state agencies, tribes, industry, and scientists
      from academic research and environmental organizations is establishing a
      national, policy-relevant mercury monitoring network, called MercNet, to address
      key questions concerning changes in anthropogenic mercury emissions and
      deposition, associated linkages to ecosystem effects, and recovery from mercury
      contamination. This network would quantify mercury in the atmosphere, land,
      water, and biota in terrestrial, freshwater, and coastal ecosystems to provide a
      national scientific capability for evaluating the benefits and effectiveness of
      emission controls. Program development began with two workshops, convened to
      establish network goals, to select key indicators for monitoring, to propose a
      geographic network of monitoring sites, and to design a monitoring plan. MercNet
      relies strongly on multi-institutional partnerships to secure the capabilities
      and comprehensive data that are needed to develop, calibrate, and refine
      predictive mercury models and to guide effective management. Ongoing
      collaborative efforts include the: (1) development of regional multi-media
      databases on mercury in the Laurentian Great Lakes, northeastern United States,
      and eastern Canada; (2) syntheses and reporting of these data for the scientific
      and policy communities; and (3) evaluation of potential monitoring sites. The
      MercNet approach could be applied to the development of other monitoring
      programs, such as emerging efforts to monitor and assess global mercury emission
      controls.

PMID- 21901444
TI  - Ability of the oriental fruit moth Grapholita molesta (Lepidoptera: Tortricidae)
      to detoxify juglone, the main secondary metabolite of the non-host plant walnut.
AB  - Many plant species produce toxic secondary metabolites that limit attacks by
      herbivorous insects, and may thereby constrain insect expansion to new hosts.
      Walnut is a host for the codling moth Cydia pomonella, which efficiently
      detoxifies the main walnut defensive compound juglone (5-hydroxy-1,4
      naphthoquinone). The oriental fruit moth Grapholita molesta, which also belongs
      to the tribe Grapholitini, does not feed on walnut. We tested the performance of
      G. molesta, a highly invasive species, on artificial diets containing juglone at
      levels mimicking those found in walnut over the growing season. Juglone-fed G.
      molesta survived relatively well to adulthood, but larval and adult body weights
      were reduced, and larval developmental time was prolonged in a dose-dependent
      fashion. Chemical analysis of frass from larvae that had been fed a juglone
      containing diet suggests that G. molesta reduces juglone to non-toxic 1,4,5
      trihydroxynaphthalene in its gut. This unexpected tolerance of G. molesta to high
      levels of juglone may facilitate expansion of the host range beyond the current
      rosacean fruit trees used by this invasive pest.

PMID- 21901445
TI  - Hepatitis B and liver cancer among three Asian American sub-groups: a focus group
      inquiry.
AB  - Prevalence of hepatitis B among Asian Americans is higher than for any other
      ethnic group in the United States. Since more than 50% of liver cancer is
      hepatitis B related, the burden of morbidity and mortality is extremely high
      among Asian Americans, highlighting the need for culturally appropriate
      interventions. We conducted focus groups (n = 8) with a total of 58 Korean,
      Vietnamese, and Chinese immigrants in Maryland to explore knowledge, awareness
      and perceived barriers toward hepatitis B screening and vaccinations. Thematic
      analysis uncovered generally low levels of knowledge and awareness of hepatitis B
      risks, screening, and vaccination; inter-generational differences; and barriers
      to prevention. Some differences arose across ethnic groups, particularly toward
      perceived orientation to preventive activities and the role of religious groups.
      High rates of hepatitis B infection among Asian Americans highlight the need for
      tailored interventions. These findings may assist policy strategists in
      implementing interventions that will facilitate the integration and scale-up of
      hepatitis B education, screening, and vaccination campaigns.

PMID- 21901446
TI  - Perspectives on preventive health care and barriers to breast cancer screening
      among Iraqi women refugees.
AB  - Since the Iraq war began in 2003, over 4 million Iraqis have been displaced.
      Little is known about preventive cancer care in this population, but stark
      disparities have been documented. The purpose of this study was to assess the
      perspectives of Iraqi women refugees on preventive care and perceived barriers to
      breast cancer screening. Interviews were conducted in Arabic with twenty Iraqi
      refugee women by a bilingual (English/Arabic) medical student, transcribed,
      translated and coded according to established qualitative content and thematic
      analysis procedures. Psychosocial barriers, culturally mediated beliefs, and
      health consequences of war were identified as major themes, ultimately showing
      what factors, alone and collectively, have impeded Iraqi refugee women's ability
      and motivation to obtain breast cancer screening. To improve cancer prevention
      and decrease disparities in care in this most vulnerable population, culturally
      appropriate health education and outreach programs, as well as further community
      level targeted studies, are needed.

PMID- 21901447
TI  - Supporting Latino communities' natural helpers: a case study of promotoras in a
      research capacity building course.
AB  - Promotores have unique access to underserved and hard-to-reach Latino communities
      facing health disparities. Although promotores are involved in community change,
      they rarely receive training that gives them the skills to be partners in
      research. We present a case study of promotoras who participated in a research
      capacity building course focused on assessing community health needs. Data comes
      from course application surveys, follow-up notes, and narratives from qualitative
      phone interviews of eight promotoras. Content analysis drawing from grounded
      theory was conducted to identify and describe emerging themes. Four themes
      emerged as promotoras discussed their experience learning basic research skills
      and teaching others: (1) challenges, (2) support, (3) building capacity, and (4)
      using research. Promotores play an important role in the health of Latino
      communities and are increasingly asked to participate in research processes;
      however they have few opportunities for training and professional development in
      this area. Capacity building opportunities for promotores need to be tailored to
      their needs and provide them with support. Fostering collaboration between
      promotores and partnering with local community-based organizations can help
      facilitate needed research skill-building among promotores.

PMID- 21901448
TI  - Quelling the storm: utilization of sphingosine-1-phosphate receptor signaling to
      ameliorate influenza virus-induced cytokine storm.
AB  - Initial and early tissue injury associated with severe influenza virus infection
      is the result of both virus-mediated lysis of infected pulmonary cells coupled
      with an exuberant immune response generated against the virus. The excessive host
      immune response associated with influenza virus infection has been termed
      "cytokine storm." Therapies that target virus replication are available; however,
      the selective pressure by such antiviral drugs on the virus often results in
      mutation and the escape of virus progeny now resistant to the antiviral regimen,
      thereby rendering such treatments ineffective. This event highlights the
      necessity for developing novel methods to combat morbidity and mortality caused
      by influenza virus infection. One potential method is restricting the host's
      immune response. However, prior treatment regimens employing drugs like
      corticosteroids that globally suppress the host's immune response were found
      unsatisfactory in large part because they disrupted the host's ability to control
      virus replication. Here, we discuss a novel therapy that utilizes sphingosine-1
      phosphate (S1P) receptor signaling that has the ability to significantly limit
      immunopathologic injury caused by the host's innate and adaptive immune response,
      thereby significantly aborting morbidity and mortality associated with influenza
      virus infection. Moreover, S1P analog therapy allows for sufficient anti
      influenza T cell and antibody formation to control infection. We review the anti
      inflammatory effects of S1P signaling pathways and how modulation of these
      pathways during influenza virus infection restricts immunopathology. Finally, we
      discuss that combinatorial administration of S1P simultaneously with a current
      antiviral enhances the treatment efficacy for virulent influenza virus infections
      above that of either drug treatment alone. Interestingly, the scope of S1P
      receptor therapy reported here is likely to extend beyond influenza virus
      infection and could prove useful for the treatment of multiple maladies like
      other viral infections and autoimmune diseases where the host's inflammatory
      response is a major component in the disease process.

PMID- 21901449
TI  - Cervical collaterals may protect against stroke after blunt vertebral artery
      injury.
AB  - The incidence of ischemic stroke reported after blunt vertebral artery injury is
      lower than that reported after blunt carotid artery injury. Unlike the carotid
      arteries, the vertebral arteries receive collateral blood flow through ascending
      cervical branches in addition to a convergent arterial supply with the
      contralateral vertebral artery. We hypothesize that the incidence of stroke after
      vertebral artery injury is less than after carotid artery injury in part because
      of reconstitution of vertebral arteries by cervical collaterals. A retrospective
      blinded interpretation of angiographic studies in 46 patients with blunt
      vertebral injury was performed to assess for presence and grade of vertebral
      artery injury and for the presence of reconstitution of the vessel via cervical
      collaterals. Follow-up CT scans from the same patients were evaluated for the
      presence of posterior circulation strokes. There were 55 injured vertebral
      arteries in the 46 patients, of whom 8 experienced posterior fossa strokes. Two
      tailed Fisher exact probability test evaluating the hypothesis that patients with
      vertebral artery collaterals were less likely to experience posterior fossa
      strokes reached significance, p < 0.05. Of patients with occlusive (grades IV and
      V) injuries, those with collateral vessels were significantly less likely to
      experience posterior fossa strokes (p < 0.01). This result may be considered when
      weighing the potential risks and benefits of antiplatelet or anticoagulation
      therapy in patients with occlusive blunt vertebral artery injury.

PMID- 21901450
TI  - Microsatellite instability in metastatic colorectal cancer: a review of
      pathology, response to chemotherapy and clinical outcome.
AB  - Approximately 10% of colorectal carcinomas demonstrate microsatellite instability
      (MSI). Distinct from the majority of colorectal cancers with chromosomal
      instability (CIN) which harbour allelic imbalance from chromosomal polyploidy and
      aneuploidy, MSI tumours retain intact chromosomal numbers but contain
      microsatellite repeats due to deficiency in mismatch repair which are thought to
      contribute to the early steps of tumourigenesis in colorectal cancer. While
      emerging clinical data has highlighted improved prognosis of tumours with MSI in
      early colorectal cancer and potentially circumventing the need for adjuvant
      chemotherapy, the implications of MSI deficiency in metastatic colorectal cancer
      (mCRC) remain uncertain. In order to assess the significance of MSI in mCRC, a
      broad literature review was carried out through online PubMed search on published
      articles encompassing pathological and clinical papers. This included
      pathological studies identifying the correlation with MSI status between primary
      sites and metastases, and chemotherapeutic studies assessing the impact of
      fluoropyrimidine-, irinotecan- and oxaliplatin-based regimens on mCRC with MSI.

PMID- 21901451
TI  - Rhythmic arm cycling differentially modulates stretch and H-reflex amplitudes in
      soleus muscle.
AB  - During rhythmic arm cycling, soleus H-reflex amplitudes are reduced by modulation
      of group Ia presynaptic inhibition. This suppression of reflex amplitude is
      graded to the frequency of arm cycling with a threshold of 0.8 Hz. Despite the
      data on modulation of the soleus H-reflex amplitude induced by rhythmic arm
      cycling, comparatively little is known about the modulation of stretch reflexes
      due to remote limb movement. Therefore, the present study was intended to explore
      the effect of arm cycling on stretch and H-reflex amplitudes in the soleus
      muscle. In so doing, additional information on the mechanism of action during
      rhythmic arm cycling would be revealed. Although both reflexes share the same
      afferent pathway, we hypothesized that stretch reflex amplitudes would be less
      suppressed by arm cycling because they are less inhibited by presynaptic
      inhibition. Failure to reject this hypothesis would add additional strength to
      the argument that Ia presynaptic inhibition is the mechanism modulating soleus H
      reflex amplitude during rhythmic arm cycling. Participants were seated in a
      customized chair with feet strapped to footplates. Three motor tasks were
      performed: static control trials and arm cycling at 1 and 2 Hz. Soleus H-reflexes
      were evoked using single 1 ms pulses of electrical stimulation delivered to the
      tibial nerve at the popliteal fossa. A constant M-wave and ~6% MVC activation of
      soleus were maintained across conditions. Stretch reflexes were evoked using a
      single sinusoidal pulse at 100 Hz given by a vibratory shaker placed over the
      triceps surae tendon and controlled by a custom-written LabView program. Results
      demonstrated that rhythmic arm cycling that was effective for conditioning soleus
      H-reflexes did not show a suppressive effect on the amplitude of the soleus
      stretch reflex. We suggest this indicates that stretch reflexes are less
      sensitive to conditioning by rhythmic arm movement, as compared to H-reflexes,
      due to the relative insensitivity to Ia presynaptic inhibition.

PMID- 21901452
TI  - Comment on: Exp Brain Res. 2011 May 5th. Transcranial magnetic stimulation of
      macaque frontal eye fields decreases saccadic reaction time. Gerits A, Ruff CC,
      Guipponi O, Wenderoth N, Driver J, Vanduffel W.

PMID- 21901453
TI  - Evidence of sound symbolism in simple vocalizations.
AB  - The question of the arbitrariness of language is among the oldest in cognitive
      sciences, and it relates to the nature of the associations between vocal sounds
      and their meaning. Growing evidence seems to support sound symbolism, claiming
      for a naturally constrained mapping of meaning into sounds. Most of such
      evidence, however, comes from studies based on the interpretation of pseudowords,
      and to date, there is little empirical evidence that sound symbolism can affect
      phonatory behavior. In the present study, we asked participants to utter the
      letter /a/ in response to visual stimuli varying in shape, luminance, and size,
      and we observed consistent sound symbolic effects on vocalizations. Utterances'
      loudness was modulated by stimulus shape and luminance. Moreover, stimulus shape
      consistently modulated the frequency of the third formant (F3). This finding
      reveals an automatic mapping of specific visual attributes into phonological
      features of vocalizations. Furthermore, it suggests that sound-meaning
      associations are reciprocal, affecting active (production) as well as passive
      (comprehension) linguistic behavior.

PMID- 21901454
TI  - Anticipation of future events improves the ability to estimate elapsed time.
AB  - An accurate estimate of elapsed time is essential for anticipating the timing of
      future events. Here, we show that the ability to estimate elapsed time on a
      reaction time (RT) task improved with training during which human participants
      learned to anticipate the onset of a "Go" signal. In each trial, a warning signal
      preceded the Go signal by a temporal interval (i.e., foreperiod). The duration of
      the foreperiod was randomly drawn from a rectangular distribution (1-2 s).
      Participants were required to initiate a response immediately after the Go signal
      and performed the task for 480 trials/day for 12 days. Anticipation should have
      been governed by the probability that the Go signal would occur (hazard rate),
      which increased for longer foreperiods. Indeed, RTs decreased for longer
      foreperiods and were inversely related to the hazard rate. The pattern of RT
      decrease was well explained by the subjective hazard rate, which was formalized
      based on the assumption that the uncertainty of estimates of elapsed time scales
      with time (Weber's law). Notably, RTs demonstrated a more linear decrease as a
      function of foreperiod in LATE compared with EARLY training sessions. This
      involved a decrease in the Weber fraction used in the subjective hazard rate. The
      results indicate that the uncertainty associated with estimating elapsed time was
      reduced as participants learned and used the hazard rate to anticipate the onset
      of the Go signal. This finding suggests that the ability to estimate elapsed time
      improves with training on behavioral tasks that implicitly engage timing
      mechanisms.

PMID- 21901457
TI  - A focus group study of predictors of relapse in electronic gaming machine problem
      gambling, part 1: factors that 'push' towards relapse.
AB  - This study aimed to develop an empirically based description of relapse in
      Electronic Gaming Machine problem gambling. In this paper the authors describe
      part one of a two part, linked relapse process: the 'push' towards relapse. In
      this two-part process, factors interact sequentially and simultaneously within
      the problem gambler to produce a series of mental and behavioural events that
      ends with relapse when the 'push' overcomes 'pull' (part one); or as described in
      part two, continued abstinence when 'pull' overcomes 'push'. In the second paper,
      the authors describe how interacting factors 'pull' the problem gambler away from
      relapse. This study used four focus groups comprising thirty participants who
      were gamblers, gamblers' significant others, therapists and counsellors. The
      groups were recorded, recordings were then transcribed and analysed using
      thematic, textual analysis. With the large number of variables considered to be
      related to relapse in problem gamblers, five key factors emerged that 'push' the
      gambler towards relapse. These were urge, erroneous cognitions about the outcomes
      of gambling, negative affect, dysfunctional relationships and environmental
      gambling triggers. Two theories emerged: (1) each relapse episode comprised a
      sequence of mental and behavioural events, which evolves over time and was
      modified by factors that 'push' this sequence towards relapse and (2) a number of
      gamblers develop an altered state of consciousness during relapse described as
      the 'zone' which prolongs the relapse.

PMID- 21901458
TI  - A rapid fluorescence polarization immunoassay for the determination of T-2 and HT
      2 toxins in wheat.
AB  - A rapid fluorescence polarization (FP) immunoassay has been developed for the
      simultaneous determination of T-2 and HT-2 toxins in naturally contaminated wheat
      samples. Syntheses of four fluorescein-labelled T-2 or HT-2 toxin tracers were
      carried out and their binding response with seven monoclonal antibodies was
      evaluated. The most sensitive antibody-tracer combination was obtained by using
      an HT-2-specific antibody and a fluorescein-HT-2 tracer. The developed
      competitive FP immunoassay in solution showed high cross-reactivity for T-2 toxin
      (CR% = 100%) while a very low CR% for neosolaniol (0.12%) and no cross-reactivity
      with other mycotoxins frequently occurring in wheat. A rapid extraction procedure
      using 90% methanol was applied to wheat samples prior to FP immunoassay. The
      average recovery from spiked wheat samples (50 to 200 MUg kg(-1)) was 96% with
      relative standard deviation generally lower than 8%. A limit of detection of 8
      MUg kg(-1) for the combined toxins was determined. Comparative analyses of 45
      naturally contaminated and spiked wheat samples by both the FP immunoassay and
      high-performance liquid chromatography/immunoaffinity clean-up showed a good
      correlation (r = 0.964). These results, combined with the rapidity (10 min) and
      simplicity of the assay, show that this method is suitable for high throughput
      screening as well as for quantitative determination of T-2 and HT-2 toxins in
      wheat.

PMID- 21901459
TI  - Characterization of currently marketed heparin products: analysis of molecular
      weight and heparinase-I digest patterns.
AB  - We evaluated polyacrylamide gel electrophoresis (PAGE) and size exclusion
      chromatography coupled with multi-angle laser light scattering (SEC-MALLS)
      approaches to determine weight-average molecular weight (M(w)) and polydispersity
      (PD) of heparins. A set of unfractionated heparin sodium (UFH) and low-molecular
      weight heparin (LMWH) samples obtained from nine manufacturers which supply the
      US market were assessed. For SEC-MALLS, we measured values for water content,
      refractive index increment (dn/dc), and the second virial coefficient (A(2)) for
      each sample prior to molecular weight assessment. For UFH, a mean +/- standard
      deviation value for M(w) of 16,773 +/- 797 was observed with a range of 15,620 to
      18,363 (n = 20, run in triplicate). For LMWHs by SEC-MALLS, we measured mean M(w)
      values for dalteparin, tinzaparin, and enoxaparin of 6,717 +/- 71 (n = 4), 6,670
      +/- 417 (n = 3), and 3,959 +/- 145 (n = 3), respectively. PAGE analysis of the
      same UFH, dalteparin, tinzaparin, and enoxaparin samples showed values of 16,135
      +/- 643 (n = 20), 5,845 +/- 45 (n = 4), 6,049 +/- 95 (n = 3), and 4,772 +/- 69 (n
      = 3), respectively. These orthogonal measurements are the first M(w) results
      obtained with a large heparin sample set on product being marketed after the
      heparin crisis of 2008 changed the level of scrutiny of this drug class. In this
      study, we compare our new data set to samples analyzed over 10 years earlier. In
      addition, we found that the PAGE analysis of heparinase digested UFH and neat
      LMWH samples yield characteristic patterns that provide a facile approach for
      identification and assessment of drug quality and uniformity.

PMID- 21901460
TI  - Determination of the binding epitope of lidocaine with AGP: minimizing the
      effects of nonspecific binding in saturation transfer difference experiments.
AB  - The ligand epitope map and the effect of nonspecific binding is assessed for
      lidocaine binding to alpha(1)-acid glycoprotein using the saturation transfer
      difference nuclear magnetic resonance experiment performed as a function of the
      ligand/protein ratio. The experimental design tested two different approaches for
      preparing solutions with various ligand/protein ratios; holding the protein
      concentration constant and increasing the ligand concentration; and holding the
      ligand concentration constant while decreasing the protein concentration.
      Nonspecific binding effects were more prevalent in experiments in which the
      ligand concentration was increased, although spectra with higher signal-to-noise
      ratios were obtained under these conditions. The epitope map determined for
      achiral lidocaine is compared with previously determined results for the (R)- and
      (S)-enantiomers of propranolol. The weaker binding affinity of lidocaine may be
      partially attributed to steric hindrance by the lidocaine N-ethyl groups which
      may prevent close contact of the lidocaine amine with the negatively charged
      amino acids at the apex of the protein binding pocket.

PMID- 21901461
TI  - Separation of alpha-tocotrienol oxidation products and eight tocochromanols by
      HPLC with DAD and fluorescence detection and identification of unknown peaks by
      DAD, PBI-EIMS, FTIR, and NMR.
AB  - Tocotrienols, like tocopherols, are members of the vitamin E family. While
      tocopherols (T) have been studied intensively, only recently have tocotrienols
      (T3) received increased attention due to their special health benefits. However,
      these positive attributes of T3 are probably lost as a result of degradation
      during food storage and processing, and there is little information about their
      oxidation products. Of particular interest are the oxidation products of alpha
      tocotrienol (alpha-T3) as this is the least thermostable T3 isomer with the
      highest rate of degradation. The objective of this study was therefore to develop
      a reliable method for the determination of the most important oxidation products
      of alpha-T3 along with other tocochromanol isomers. We developed a high
      performance liquid chromatography method with diode array detection, fluorescence
      detection, and a particle beam interface electron impact mass spectroscopy in
      order to separate the most important oxidation products of alpha-T3 (alpha-T3
      spirodimers/spirotrimers, alpha-tocotrienoldihydroxy dimer, 7-formyl-beta
      tocotrienol (7-FbetaT3), 5-formyl-gamma-tocotrienol (5-FgammaT3), alpha
      tocotrienolquinone (alpha-T3Q), and alpha-T3Q dimers and alpha-tocotrienolquinone
      epoxides (alpha-T3QE)) from eight tocochromanol isomers. Furthermore, we sought
      to identify the as yet unknown oxidation products 5-FgammaT3, 7-FbetaT3, alpha
      T3Q-dimer, and alpha-T3QE. Of these, 5-FgammaT3 was fully characterized by
      Fourier transform infrared spectroscopy and (1)H and (13)C nuclear magnetic
      resonance spectroscopy.

PMID- 21901462
TI  - On the utility of predictive chromatography to complement mass spectrometry based
      intact protein identification.
AB  - The amino acid sequence determines the individual protein three-dimensional
      structure and its functioning in an organism. Therefore, "reading" a protein
      sequence and determining its changes due to mutations or post-translational
      modifications is one of the objectives of proteomic experiments. The commonly
      utilized approach is gradient high-performance liquid chromatography (HPLC) in
      combination with tandem mass spectrometry. While serving as a way to simplify the
      protein mixture, the liquid chromatography may be an additional analytical tool
      providing complementary information about the protein structure. Previous
      attempts to develop "predictive" HPLC for large biomacromolecules were limited by
      empirically derived equations based purely on the adsorption mechanisms of the
      retention and applicable to relatively small polypeptide molecules. A mechanism
      of the large biomacromolecule retention in reversed-phase gradient HPLC was
      described recently in thermodynamics terms by the analytical model of liquid
      chromatography at critical conditions (BioLCCC). In this work, we applied the
      BioLCCC model to predict retention of the intact proteins as well as their large
      proteolytic peptides separated under different HPLC conditions. The specific aim
      of these proof-of-principle studies was to demonstrate the feasibility of using
      "predictive" HPLC as a complementary tool to support the analysis of identified
      intact proteins in top-down, middle-down, and/or targeted selected reaction
      monitoring (SRM)-based proteomic experiments.

PMID- 21901463
TI  - Hydrodynamic chromatography: packed columns, multiple detectors, and
      microcapillaries.
AB  - Hydrodynamic chromatography (HDC) is a liquid chromatographic technique that
      separates analytes on the basis of their size in solution. Separation can be
      conducted either in an open tube or in a column packed with inert, nonporous
      beads. In HDC, larger analytes elute first and smaller ones later, due to
      preferential sampling of the streamlines of flow in the open tube or in the
      interstitial medium of the packed column. Because of the low shear rates
      experienced in HDC, coupled with the wealth of information obtained when
      employing a multiplicity of detection methods, the technique has experienced a
      resurgence in recent years in both the particle sizing and macromolecular arenas,
      where it can provide information on the mutual interdependence of molar mass,
      size, shape, and compactness. Additionally, microcapillary HDC is also gaining
      popularity amongst the bioanalytical community, who have employed the technique,
      inter alia, to separate DNA fragments over a base pair range spanning four orders
      in magnitude. Here, examples from the literature are used to show how HDC has
      been applied in each of the aforementioned areas, explaining the information that
      can be obtained from various detector combinations, and opining on the future of
      the technique.

PMID- 21901464
TI  - Chemometric evaluation of nine alcohol biomarkers in a large population of
      clinically-classified subjects: pre-eminence of ethyl glucuronide concentration
      in hair for confirmatory classification.
AB  - An important goal of forensic and clinical toxicology is to identify biological
      markers of ethanol consumption that allow an objective diagnosis of chronic
      alcohol misuse. Blood and head hair samples were collected from 175 subjects
      objectively classified as non-drinkers (N=65), social drinkers (N=51) and active
      heavy drinkers (N=59)-and analyzed to determine eight traditional indirect
      biomarkers of ethanol consumption [aspartate aminotransferase (AST), alanine
      aminotransferase (ALT), gamma-glutamyltransferase (gamma-GT), alkaline
      phosphatase (ALP), mean corpuscular volume (MCV), carbohydrate-deficient
      transferrin (CDT), and cholesterol and triglycerides in blood] and one direct
      biomarker [ethyl glucuronide (EtG) in head hair]. The experimental values
      obtained from these determinations were submitted to statistical evaluations. In
      particular, Kruskal-Wallis, Mann-Whitney and ROC curve analyses, together with
      principal component analysis (PCA), allowed the diagnostic performances of the
      various biomarkers to be evaluated and compared consistently. From these
      evaluations, it was possible to deduce that EtG measured in head hair is the only
      biomarker that can conclusively discriminate active heavy drinkers from social
      and non-drinkers, using a cut-off value of 30 pg/mg. In contrast, a few indirect
      biomarkers such as ALP, cholesterol, and triglycerides showed extremely low
      diagnostic abilities and may convey misleading information. AST and ALT proved to
      be highly correlated and exhibited quite low sensitivity and specificity.
      Consequently, either of these parameters can be discarded without compromising
      the classification efficiency. Among the indirect biomarkers, gamma-GT provided
      the highest diagnostic accuracy, while CDT and MCV yielded high specificity but
      low sensitivity. It was therefore concluded that EtG in head hair is the only
      biomarker capable of supporting a confirmatory diagnosis of chronic alcohol abuse
      in both forensic and clinical practice, while it was found that gamma-GT, CDT,
      MCV, and AST--whether used alone or in combination--do not allow the conclusive
      classification of subjects according to ethanol consumption. However, a
      diagnostic strategy combining these four parameters could be formulated in order
      to create a multivariate model capable of screening suspected active heavy
      drinkers.

PMID- 21901465
TI  - [Indications for laparoscopic pancreas operations: results of a consensus
      conference and the previous laparoscopic pancreas register].
AB  - Laparoscopic pancreatic surgery is not common practice in Germany and is only
      carried out in approximately 20 clinics but with an increasing trend. The reasons
      for this are manifold, such as the current selection of patients and both skills
      in laparoscopic and pancreatic surgery are necessary to perform this operation
      safely. In 2008 a registry called "Laparoscopic pancreatic surgery" was
      implemented to collect enough data in Germany to find out whether the resection
      is safe, feasible and beneficial for the patient.For further development of new
      laparoscopic techniques new data is needed. A group of experts performing
      laparoscopic pancreatic surgery in Germany supplied their data for the German
      registry for laparoscopic pancreatic resection and a consensus conference about
      the indications became necessary. This consensus conference discussed in
      particular the indications for laparoscopic pancreatic resection. A consensus was
      found by all members of the conference utilizing currently available evidence
      based data.It was suggested that all data of laparoscopic pancreatic surgery
      should be evaluated in the German Registry. A consensus was made which diseases
      were either suitable for laparoscopic resection or not suitable or suitable in
      selected cases.

PMID- 21901466
TI  - [Blood-borne infections and the pregnant health care worker. Risks and preventive
      measures].
AB  - Due to the increasing proportion of women in health care, as well as changes in
      working conditions (implementation of safety devices, minimally
      invasive/endoscopic procedures) the question arises whether the applicable laws
      and regulations for the protection of working mothers are outdated and should be
      updated.Individual risk analysis, as well as the inclusion of the pregnant health
      care worker in the decision-making process with regard to continuation or
      modification of the work practice serves as a protection of the expectant mother
      and unborn child and allows a continuation of the occupational activities.

PMID- 21901467
TI  - [Femur reconstruction using combined autologous fibula transfer and humeral
      allograft].
AB  - Wide resection far into the femoral metaphysis may be required to treat malignant
      bone tumors in the pediatric and adolescent patient population. Biological
      reconstruction using a free, vascularized fibular graft is a well-established
      surgical technique. A short remaining femoral medullary canal and a relatively
      small fibula diameter can make fixation of the vascularized bone transfer
      difficult. Stable fixation and short fusion times, however, can be achieved with
      the use of an additional humeral allograft and plate osteosynthesis.

PMID- 21901468
TI  - [Adenocarcinoma of small bowel. An underdiagnosed disease].
AB  - BACKGROUND: Small bowel adenocarcinoma is a rare disease. The diagnosis is often
      disguised by nonspecific and varied presenting symptoms. Adenocarcinoma of the
      small bowel is typically detected at a late stage and with a poor prognosis.
      PATIENTS AND METHODS: The records of 42 patients with small bowel adenocarcinomas
      diagnosed in 2 surgical clinics between 1995 and 2009 were reviewed for patient
      and tumor characteristics, treatment effects and survival. RESULTS: The tumor
      locations were the duodenum (50%), jejunum (38%) and ileum (12%). In comparison
      to patients seen before 2004 the observed frequency of emergency operations or
      palliative procedures as well as stage distribution did not change. The median
      overall survival was 19 months with a 5-year overall survival of 20%. For
      patients with resections, reduced performance status, higher stage and residual
      disease after resection predicted decreased overall survival in univariate
      analysis. Residual disease and pT category were predictive of survival in
      multivariate analysis. CONCLUSION: Complete resection provides the only means of
      a cure. In cases where curative resection cannot be performed the prognosis
      remains poor. Further study on the methods for early detection and effective
      adjuvant chemotherapy should be investigated, however, the available data are
      limited.

PMID- 21901469
TI  - [Endovascular therapy of chronic mesenteric ischemia].
AB  - Arteriosclerosis is the most common cause of chronic mesenteric ischemia, which
      is characterized by postprandial pain, unintentional weight loss and food
      avoidance. The use of endovascular techniques for revascularization of chronic
      stenoses and occlusions of the mesenteric arteries has rapidly increased over the
      last 10 years. The results of endovascular therapy have shown less morbidity and
      mortality compared to open surgical procedures, such as bypass and
      thrombendarterectomy. Early publications have reported higher rates of
      restenosis, symptomatic recurrence and reinterventions but recent case series
      show comparable patency rates. This article reviews visceral arterial anatomy and
      anomalies and endovascular techniques for the revascularization of mesenteric
      arteries.

PMID- 21901470
TI  - Polyamines modulate epithelial-to-mesenchymal transition.
AB  - Epithelial-to-mesenchymal transition and mesenchymal-to-epithelial transition are
      biologic processes responsible for conversion of epithelial cells into a
      mesenchymal phenotype or viceversa, respectively. They occur during embryo- and
      foetal-development and, in adult organisms, are involved in wound healing, in the
      genesis and progression of organ fibrosis as well as in the invasiveness of
      epithelial cancer cells. The key event of epithelial-to-mesenchymal transition is
      the loss of E-cadherin expression due to repressor activity of the
      transcriptional factor Snai1. Intracellular Snai1 levels are controlled through
      translational and post-translational events such as phosphorylation and de
      phosphorylation, potentially modulated by polyamine content. Epithelial MDCK
      cells exposed to TGF-beta(1) acquired a fibroblastoid phenotype and expressed
      mesenchymal markers. These changes were emphasized in cells that were also
      exposed to DFMO in order to decrease the intracellular levels of polyamines.
      Addition of exogenous polyamines almost completely abolished the combined action
      of DFMO and TGF-beta(1) and rapidly reverted to epithelial phenotype MDCK cells
      previously undergone to mesenchymal phenotype. Nuclear extracts of cells treated
      with DFMO + TGF-beta(1) revealed the presence of Snai1 immunopositive bands in a
      range of molecular weight between 55 and 72 kDa, with additional positive bands
      detected at MW greater than 170 kDa. Same bands resulted positive to anti-Sumo
      2/3 antibody, suggesting that an intracellular low level of polyamines favours
      Snai1 nuclear accumulation under the form of polysumoylated proteins.

PMID- 21901471
TI  - Chronic exposure to agmatine results in the selection of agmatine-resistant
      hepatoma cells.
AB  - During our study of the cytostatic effect of agmatine, we were able to isolate an
      agmatine resistant clone from a parental hepatoma cell line, HTC. These cells,
      called Agres, had slower growth rate than the parental cells when cultured in
      normal medium. The modification in polyamine content induced by agmatine was much
      lower in these cells and ornithine decarboxylase, S-adenosylmethionine
      decarboxylase and spermidine/spermine acetyltransferase activities were much less
      affected. By investigating the mechanism responsible for these modifications, it
      was shown that agmatine and polyamines were not taken up by Agres cells. Their
      resistance to the antiproliferative effects of agmatine may thus arise from a
      lack of the polyamine transport system. Moreover, Agres cells were able to take
      up both glutamic acid and arginine at a rate significantly higher than that
      detected for HTC cells, most likely to provide components for compensatory
      increase of PA synthesis. These results emphasize the importance of polyamine
      transport for cell growth.

PMID- 21901472
TI  - Site-directed mutagenesis and feedback-resistant N-acetyl-L-glutamate kinase
      (NAGK) increase Corynebacterium crenatum L-arginine production.
AB  - N-acetyl-L-glutamate kinase (EC 2.7.2.8) is first committed in the specific L
      arginine pathway of Corynebacterium sp. A limited increase of L-arginine
      production for the argB overexpression in the engineering C. creantum SYPA-CCB
      strain indicated that L-arginine feedback inhibition plays an influence on the L
      arginine production. In this study, we have performed site-directed mutagenesis
      of the key enzyme (NAGK) and the three mutations (E19R, H26E and H268D) exhibited
      the increase of I0.5R efficiently. Thereby, the multi-mutated NAGKM3 (including
      E19R/H26E/H268D) was generated and its I0.5R of L-arginine of the mutant was
      increased remarkably, whereas the NAGK enzyme activities did not declined. To get
      a feedback-resistant and robust L-arginine producer, the engineered strains SYPA
      CCBM3 were constructed. Introducing the argBM3 gene enabled the NAGK enzyme
      activity insensitive to the intracellular arginine concentrations resulted in an
      enhanced arginine biosynthesis flux and decreased formation of by-products. The L
      arginine synthesis was largely enhanced due to the overexpression of the argBM3,
      which is resistant to feedback resistant by L-arginine. Thus L-arginine
      production could reach 45.6 g/l, about 41.7% higher compared with the initial
      strain. This is an example of up-modulation of the flux through the L-arginine
      metabolic pathway by deregulating the key enzyme of the pathway.

PMID- 21901473
TI  - Federal state differentials in the efficiency of health production in Germany: an
      artifact of spatial dependence?
AB  - Due to regional competition and patient migration, the efficiency of healthcare
      provision at the regional level is subject to spatial dependence. We address this
      issue by applying a spatial autoregressive model to longitudinal data from
      Germany at the district ('Kreis') level. The empirical model is specified to
      explain efficiency scores, which we derive through non-parametric order-m
      efficiency analysis of regional health production. The focus is on the role of
      health policy of federal states ('Bundeslander') for district efficiency.
      Regression results reveal significant spatial spillover effects. Notably,
      accounting for spatial dependence does not decrease but increases the estimated
      effect of federal states on district efficiency. It appears that genuinely more
      efficient states are less affected by positive efficiency spillovers, so that
      taking into account spatial dependence clarifies the importance of health policy
      at the state level.

PMID- 21901474
TI  - Re: The calcium scare: what would Austin Bradford Hill have thought?

PMID- 21901475
TI  - Fracture risk assessment in patients with chronic kidney disease.
AB  - Fractures are common in patients with chronic kidney disease (CKD) and associated
      with substantially high morbidity and mortality. Bone mass measurements are
      commonly used to assess fracture risk in the general population, but the utility
      of these measurements in patients with CKD, and specifically among those on
      hemodialysis, is unclear. This review will outline the epidemiology and etiology
      of fractures in patients with CKD with a particular emphasis on men and women on
      hemodialysis. As well, we will summarize the published data, which describes the
      association between risk factors for fracture (including bone mass measurements,
      biochemical markers of mineral metabolism, and muscle strength) and fractures in
      patients with CKD. Patients with CKD suffer from fractures due to impairments in
      bone quantity, bone quality, and abnormalities of neuromuscular function. There
      is a paucity of evidence on the associations between bone quality, bone turnover
      markers, neuromuscular function, and fractures in patients with CKD. Furthermore,
      the complex etiology of fractures combined with the technical limitations of bone
      mineral density testing, both by dual energy X-ray absorptiometry (DXA) and by
      peripheral quantitative tomography (pQCT), limits the clinical utility of bone
      mass measurements for fracture prediction in CKD; this is particularly true among
      patients with stages 4 and 5 CKD. Further prospective studies to identify
      noninvasive measures of bone strength that can be used for fracture risk
      assessment are needed.

PMID- 21901476
TI  - Osteoporosis medication prescribing in British Columbia and Ontario: impact of
      public drug coverage.
AB  - We compared the patterns of osteoporosis medication prescribing between two
      provinces in Canada with different public drug coverage policies. Oral
      bisphosphonates were the primary drugs used, yet access to the second-generation
      oral bisphosphonates (alendronate, risedronate) was limited in one region.
      Implications of differential access to oral bisphosphonates warrants further
      study. INTRODUCTION: Approved therapies for treating osteoporosis in Canada
      include bisphosphonates, calcitonin, denosumab, raloxifene, and teriparatide.
      However, significant variation in access to these medications through public drug
      coverage exists across Canada. We sought to compare patterns of osteoporosis
      medication prescribing between British Columbia (BC) and Ontario. METHODS: Using
      dispensing data from BC (PharmaNet) and Ontario (Ontario Drug Benefits), we
      identified all new users of osteoporosis medications aged 66 or more years from
      1995/1996 to 2008/2009. We summarized the number of new users by fiscal year,
      sex, and index drug for each province. BC data were also stratified by whether
      drugs were dispensed within or outside public PharmaCare. RESULTS: We identified
      578,254 (n = 122,653 BC) eligible new users. Overall patterns were similar
      between provinces: (1) most patients received an oral bisphosphonate (93% in BC
      and 99% in Ontario); (2) etidronate prescribing declined after 2001/2002,
      reaching a low of 41% in BC and 10% in Ontario in 2008/2009; and (3) the
      proportion of males treated increased over time, from 7% in 1996/1997 to 25% in
      2008/2009. However, we note major differences within versus outside the BC
      PharmaCare system. In particular, <2% of drugs dispensed within PharmaCare
      compared to 79% of drugs dispensed outside PharmaCare were for a second
      generation bisphosphonate (alendronate or risedronate). CONCLUSIONS: Oral
      bisphosphonates are the primary drugs used to treat osteoporosis in Canada.
      Prescribing practices changed over time as newer medications came to market, yet
      access to second-generation bisphosphonates through BC PharmaCare was limited.
      Implications of differential access to oral bisphosphonates warrants further
      study.

PMID- 21901477
TI  - Hip bone geometry in HIV/HCV-co-infected men and healthy controls.
AB  - People with both HIV and hepatitis C are more likely than those with HIV alone to
      have wrist, hip, and spine fractures. We compared hip strength between HIV/HCV-co
      infected men and healthy men and found that HIV/HCV-co-infected men had decreased
      hip strength due to lower lean body mass. INTRODUCTION: Hepatitis C co-infection
      is a risk factor for fragility fracture among HIV-infected populations. Whether
      bone strength is compromised in HIV/HCV-co-infected patients is unknown. METHODS:
      We compared dual-energy x-ray absorptiometry (DXA)-derived hip geometry, a
      measure of bone strength, in 88 HIV/HCV-co-infected men from the Johns Hopkins
      HIV Clinic to 289 men of similar age and race and without HIV or HCV from the
      Boston Area Community Health Survey/Bone Survey. Hip geometry was assessed at the
      narrow neck, intertrochanter, and shaft using hip structural analysis. Lean body
      mass (LBM), total fat mass (FM), and fat mass ratio (FMR) were measured by whole
      body DXA. Linear regression was used to identify body composition parameters that
      accounted for differences in bone strength between cohorts. RESULTS: HIV/HCV-co
      infected men had lower BMI, LBM, and FM and higher FMR compared to controls (all
      p < 0.05). At the narrow neck, significant differences were observed between
      HIV/HCV-co-infected men and controls in bone mineral density, cross-sectional
      area, section modulus, buckling ratio, and centroid position. After adjustment
      for race, age, smoking status, height, and weight, only buckling ratio and
      centroid position remained significantly different between cohorts (all p <
      0.05). Substituting LBM, FM, and FMR for weight in the multivariate model
      revealed that differences in LBM, but not FM or FMR, accounted for differences in
      all narrow neck parameters between cohorts, except buckling ratio and centroid
      position. CONCLUSION: HIV/HCV-co-infected men have compromised hip strength at
      the narrow neck compared to uninfected controls, which is attributable in large
      part to lower lean body mass.

PMID- 21901478
TI  - Is vascular calcification associated with bone mineral density and osteoporotic
      fractures in ambulatory, elderly women?
AB  - We analyzed the relationship between aortic calcification and two osteoporotic
      parameters (bone mineral density (BMD) and incident osteoporotic fractures) in
      667 ambulatory, elderly women from the Epidemiology of Osteoporosis (EPIDOS)
      cohort (mean age, 80 years; range, 72-94 years). We did not find any correlation
      between the aortic calcification score and BMD or osteoporotic fractures.
      INTRODUCTION: The aging process is associated with osteoporosis and aortic
      calcification; conditions which may have similar disease mechanisms. However, the
      relationship between these two settings remains to be elucidated. We analyzed the
      relationship between aortic calcification and osteoporotic parameters (BMD and
      incident osteoporotic fractures) in a cohort of ambulatory, elderly women.
      METHODS: The study included 667 ambulatory women from the EPIDOS cohort (mean
      age, 80 years; age range, 72-94 years). The baseline examination included bone
      investigations, a clinical and functional examination, and a comprehensive
      questionnaire on health status and lifestyle. Semiquantitative methods were used
      to determine the abdominal aortic calcification score on baseline radiographs.
      Incident fractures were recorded via postal questionnaires issued every 4 months
      for about 4 years. RESULTS: Five hundred three women (75%) had aortic
      calcification. The mean aortic calcification score was 5.5 (median, 4). During
      the follow-up period, 186 (28%) women reported one or more incident osteoporotic
      fractures. We did not find any correlation between the aortic calcification score
      on one hand and the BMD or the occurrence of incident osteoporotic fractures on
      the other. Only age and systolic blood pressure were found to be independently
      associated with the aortic calcification score. Osteoporotic fractures were
      independently associated with age and BMD. CONCLUSIONS: Osteoporosis and aortic
      calcification appear to be independent processes in a cohort of ambulatory,
      elderly women. However, potential confounding factors may be present and
      prospective studies are needed to investigate this situation further.

PMID- 21901479
TI  - Skin advanced glycation end-product accumulation is negatively associated with
      calcaneal osteo-sono assessment index among non-diabetic adult Japanese men.
AB  - This study aims to determine the relationship between advanced glycation end
      product (AGE) accumulation in skin tissue and bone strength, assessed by
      quantitative ultrasound, among healthy adult Japanese men. The results of the
      study suggest that men with higher AGE accumulation in skin tissue have a lower
      osteo-sono assessment index. INTRODUCTION: AGE accumulate in bone collagen with
      age and diabetes and decrease the mechanical properties of bone. Although
      increased AGE levels are associated with fractures among diabetic patients and
      elderly women, it is unclear whether a relationship between increased AGE levels
      and bone strength is present in apparently healthy adult males. The aim of this
      study was to determine the relationship between AGE accumulation in tissue and
      the mechanical properties of bone among adult Japanese men, using quantitative
      ultrasound as a surrogate measure of the latter. METHODS: Skin autofluorescence
      (AF), which is a noninvasive method for measuring tissue AGEs, and osteo-sono
      assessment index (OSI), which is determined by quantitative ultrasound, were
      measured in 193 adult Japanese men (median age 43 years; interquartile range 37.0
      55.0 years). RESULTS: Adjusted for age, BMI, calcium intake, physical activity,
      smoking status, and education level, log-transformed skin AF had a negative
      association with log-transformed OSI (beta = -0.218, P < 0.01). Adjusted
      geometric means (95% CI) for OSI across the tertiles of skin AF were 2.81 (2.75
      2.87) for the lowest tertile, 2.81 (2.74-2.87) for the middle tertile, and 2.66
      (2.61-2.73) for the highest tertile; thus, OSI for the highest skin AF appeared
      to be 5.0% lower than that for the lowest and middle skin AF tertiles (P < 0.01).
      CONCLUSION: Among apparently healthy adult Japanese men, those with higher skin
      AF had a lower OSI, indicating a relationship between AGE accumulation and bone
      strength. A long-term prospective study is required to clarify the causality.

PMID- 21901480
TI  - The effect of soy isoflavone on bone mineral density in postmenopausal Taiwanese
      women with bone loss: a 2-year randomized double-blind placebo-controlled study.
AB  - The treatment of 300-mg/day isoflavones (aglycone equivalents) (172.5 mg
      genistein + 127.5 mg daidzein) for 2 years failed to prevent lumbar spine and
      total proximal femur bone mineral density (BMD) from declining as compared with
      the placebo group in a randomized, double-blind, two-arm designed study enrolling
      431 postmenopausal women 45-65 years old. INTRODUCTION: This study evaluated the
      effects of soy isoflavones on bone metabolism in postmenopausal women. METHODS:
      Four hundred and thirty-one women, aged 45-65 years, orally consumed 300-mg/day
      isoflavones (aglycone equivalents) or a placebo for 2 years in a parallel group,
      randomized, double-blind, two-arm study. Each participant also ingested 600 mg of
      calcium and 125 IU of vitamin D(3) per day. The BMD of the lumbar spine and total
      proximal femur were measured using dual-energy X-ray absorptiometry at baseline
      and every half-year thereafter. Serum bone-specific alkaline phosphatase, urinary
      N-telopeptide of type 1 collagen/creatinine, and other safety assessments were
      examined regularly. RESULTS: Two hundred out of 217 subjects in the isoflavone
      group and 199 out of 214 cases in placebo group completed the treatment. Serum
      concentrations of isoflavone metabolites, genistein and daidzein, of the
      intervention group were remarkably elevated following intake of isoflavones (p <
      0.001). However, differences in the mean percentage changes of BMD throughout the
      treatment period were not statistically significant (lumbar spine, p = 0.42;
      total femur, p = 0.39) between the isoflavone and placebo groups, according to
      the generalized estimating equation (GEE) method. A significant time trend of
      bone loss was observed at both sites as assessed by the GEE method following
      repeated measurement of BMD (p < 0.001). Differences in bone marker levels were
      not significant between the two treatment groups. CONCLUSION: Treatment with 300
      mg/day isoflavones (aglycone equivalents) failed to prevent a decline in BMD in
      the lumbar spine or total femur compared with the placebo group.

PMID- 21901481
TI  - Comparable outcomes in fracture reduction and bone properties with RANKL
      inhibition and alendronate treatment in a mouse model of osteogenesis imperfecta.
AB  - We report a direct comparison of receptor activator of nuclear factor kappa B
      ligand (RANKL) inhibition (RANK-Fc) with bisphosphonate treatment (alendronate,
      ALN) from infancy through early adulthood in a mouse model of osteogenesis
      imperfecta. Both ALN and RANK-Fc decreased fracture incidence to the same degree
      with increases in metaphyseal bone volume via increased number of thinner
      trabeculae. INTRODUCTION: The potential therapeutic benefit of RANKL inhibitors
      in osteogenesis imperfecta (OI) is under investigation. We report a direct
      comparison of RANKL inhibition (RANK-Fc) with bisphosphonate treatment (ALN) from
      infancy through early adulthood in a model of OI, the oim/oim mouse. METHODS: Two
      week-old oim/oim, oim/+, and wildtype (+/+) mice were treated with RANK-Fc 1.5
      mg/kg twice per week, ALN 0.21 mg/kg/week or saline (n = 12-20 per group) for 12
      weeks. RESULTS: ALN and RANK-Fc both decreased fracture incidence (9.0 +/- 3.0
      saline 4.4 +/- 2.7 ALN, 4.3 +/- 3.0 RANK-Fc fractures per mouse). Serum TRACP-5b
      activity decreased to 65% after 1 month in all treated mice, but increased
      sacrifice with RANK-Fc to 130-200% at sacrifice. Metaphyseal density was
      significantly increased with ALN in +/+ and oim/oim mice (p < 0.05) and tended to
      increase with RANK-Fc in +/+ mice. No changes in oim/oim femur biomechanical
      parameters occurred with treatment. Both ALN and RANK-Fc significantly increased
      trabecular number (3.73 +/- 0.77 1/mm for oim/oim saline vs 7.93 +/- 0.67 ALN and
      7.34 +/- 1.38 RANK-Fc) and decreased trabecular thickness (0.045 mm +/- 0.003 for
      oim/oim saline vs 0.034 +/- 0.003 ALN and 0.032 +/- 0.002 RANK-Fc) and separation
      in all genotypes (0.28 +/- 0.08 mm for oim/oim saline vs 0.12 +/- 0.010 ALN and
      13 +/- 0.03 RANK-Fc)., with significant increase in bone volume fraction (BVF)
      with ALN, and a trend towards increased BVF in RANK-Fc. CONCLUSION: Treatment of
      oim/oim mice with either a bisphosphonate or a RANK-Fc causes similar decreases
      in fracture incidence with increases in metaphyseal bone volume via increased
      number of thinner trabeculae.

PMID- 21901482
TI  - Clinicopathological considerations in acute disseminated encephalomyelitis
      (ADEM): a fulminant case with favorable outcome.

PMID- 21901483
TI  - Chance of aneurysm in patients suspected of SAH who have a 'negative' CT scan but
      a 'positive' lumbar puncture.
AB  - In patients with sudden severe headache and a negative computed tomography (CT)
      scan, a lumbar puncture (LP) is performed to rule in or out a subarachnoid
      haemorrhage (SAH), but this procedure is under debate. In a hospital-based series
      of 30 patients with sudden headache, a negative CT scan but a positive LP
      (defined as detection of bilirubin >0.05 at wavelength 458 nm), we studied the
      chance of harbouring an aneurysm and the clinical outcome. Aneurysms were found
      in none of both patients who presented within 3 days, in 8 of the 18 (44%) who
      presented within 4-7 days and in 5 of the 10 (50%) who presented within 8-14
      days. Of the 13 patients with an aneurysm, 3 (23%) had poor outcome. In patients
      who present late after sudden headache, the yield in terms of aneurysms is high
      in those who have a positive lumbar puncture. In patients with an aneurysm as
      cause of the positive lumbar puncture, outcome is in the same range as in SAH
      patients admitted in good clinical condition.

PMID- 21901484
TI  - MoDUO1, a Duo1-like gene, is required for full virulence of the rice blast fungus
      Magnaporthe oryzae.
AB  - Duo1, a major component of the Dam1 complex which has been found in two species
      of yeast (the budding yeast Saccharomyces cerevisae and the fission yeast
      Schizosaccharomyces pombe), is involved in mitosis-related chromosome
      segregation, while its relevance to pathogenicity in filamentous fungi remains
      unclear. This report elucidated this very fact in the case of the rice blast
      fungus Magnaporthe oryzae. A gene designated MoDUO1 that encodes a Duo1-like
      homolog (MoDuo1) was discovered in the M. oryzae genome. Two types of MoDUO1
      mutants were obtained using genetic approaches of Agrobacterium-mediated gene
      disruption and homologous recombination. Both disruption and deletion of MoDUO1
      can exert profound effects on the formation pattern of conidiophores and conidial
      morphology, such as abnormal nucleic numbers in conidia and delayed extension of
      infectious hyphae. Intriguingly, plant infection assays demonstrated that
      inactivation of MoDUO1 significantly attenuates the virulence in its natural host
      rice leaves, and functional complementation can restore it. Subcellular
      localization assays showed that MoDuo1 is mainly distributed in the cytosol of
      fungal cells. Proteomics-based investigation revealed that the expression of four
      mitosis-related proteins is shut down in the MoDUO1 mutant, suggesting that
      MoDuo1 may have a function in mitosis. In light of the fact that Duo1 orthologs
      are widespread in plant and human fungal pathogens, our finding may represent a
      common mechanism underlying fungal virulence. To the best of our knowledge, this
      is the first example of linking a Duo1-like homolog to the pathogenesis of a
      pathogenic fungus, which might provide clues to additional studies on the role of
      Dam1 complex in M. oryzae and its interaction with rice.

PMID- 21901486
TI  - Infant feeding practices were not associated with breast milk HIV-1 RNA levels in
      a randomized clinical trial in Botswana.
AB  - Exclusive breastfeeding has been associated with a reduced risk of late vertical
      HIV transmission as compared to an infant diet composed of breast milk mixed with
      supplemental foods or liquids. Hypothesized mechanisms include increased
      infectivity of breast milk from mothers who practice mixed breastfeeding (MBF),
      or mechanisms such as increased gastrointestinal permeability in the infant
      caused by mixed feeding. It has been proposed that MBF may result in subclinical
      mastitis and higher breast milk HIV titers. However, little is known about the
      relationship between feeding strategy and breast milk viral load. We measured the
      HIV-1 concentration in breast milk in a sub-cohort of women enrolled in a mother
      to-child HIV transmission prevention trial (the "Mashi" study). We report no
      observed relationship between MBF and measured breast milk viral RNA load. Our
      findings suggest that the increased transmission risk associated with higher
      breast milk HIV-1 RNA during MBF is unlikely.

PMID- 21901487
TI  - Early adolescent romantic relationships and maternal approval among inner city
      Latino families.
AB  - Latino youth are at high risk for acquiring HIV during adolescence. The present
      study documented the nature of adolescent romantic relationships among 702 Latino
      eighth grade students and their mothers in the Bronx, NY. The study examined
      adolescent romantic relationships, the association between participation in such
      relationships and intentions to engage in sexual risk behavior, and maternal
      influences on adolescent's involvement in intimate behaviors in romantic
      relationships. Almost 50% of youth had been in a romantic relationship, which
      typically lasted 3-3.5 months. Mothers tended to approve of intimate behaviors
      and sexual activity in romantic relationships more so for males than females.
      Latino youth tended to underestimate maternal disapproval of a range of intimate
      behaviors, and the correlations between perceived and actual maternal approval
      were generally low in magnitude. Finally, maternal orientations towards their
      adolescent engaging in romantic relationships were associated with their child's
      intentions to have sexual intercourse in the future.

PMID- 21901488
TI  - FOXP1, an estrogen-inducible transcription factor, modulates cell proliferation
      in breast cancer cells and 5-year recurrence-free survival of patients with
      tamoxifen-treated breast cancer.
AB  - Breast cancer is primarily a hormone-dependent tumor that can be regulated by the
      status of steroid hormones, including estrogen and progesterone. Forkhead box P1
      (FOXP1) is a member of the forkhead box transcription factor family and has been
      reported to be associated with various types of tumors. In the present study, we
      investigated the expression of FOXP1 in 133 human invasive breast cancers,
      obtained by core biopsy, by immunohistochemical analysis. Nuclear
      immunoreactivity of FOXP1 was detected in 89 cases (67%) and correlated
      positively with tumor grade and hormone receptor status, including estrogen
      receptor alpha (ERalpha) and progesterone receptor, and negatively with
      pathological tumor size. In ERalpha-positive MCF-7 breast cancer cells, we
      demonstrated that FOXP1 mRNA was upregulated by estrogen and increased ERalpha
      recruitment to ER binding sites identified by ChIP-on-chip analysis within the
      FOXP1 gene region. We also demonstrated that proliferation of MCF-7 cells was
      increased by exogenously transfected FOXP1 and decreased by FOXP1-specific siRNA.
      Furthermore, FOXP1 enhanced estrogen response element-driven transcription in MCF
      7 cells. Finally, FOXP1 immunoreactivity was significantly elevated in relapse
      free breast cancer patients treated with tamoxifen. These results suggest that
      FOXP1 plays an important role in proliferation of breast cancer cells by
      modulating estrogen signaling and that FOXP1 immunoreactivity could be associated
      with the estrogen dependency of clinical breast cancers, which may predict
      favorable prognosis in the patients treated with tamoxifen.

PMID- 21901491
TI  - Resilience training and physician well-being.

PMID- 21901489
TI  - Provider characteristics, clinical-work processes and their relationship to
      discharge summary quality for sub-acute care patients.
AB  - BACKGROUND: Discharge summaries play a pivotal role in the transitional care of
      patients discharged to sub-acute care facilities, but the best ways to facilitate
      document completeness/quality remain unknown. OBJECTIVE: To examine the
      relationship among clinical-work processes, provider characteristics, and
      discharge summary content to identify approaches that promote high-quality
      discharge documentation. DESIGN: Retrospective cohort study. SUBJECTS: All hip
      fracture and stroke patients discharged to sub-acute care facilities during 2003
      2005 from a large Midwestern academic medical center (N = 489). Patients on
      hospice/comfort care were excluded. MAIN MEASURES: We abstracted 32 expert
      recommended components in four categories ('patient's medical course,'
      'functional/cognitive ability at discharge,' 'future plan of care,' and
      'name/contact information') from the discharge summaries of sample patients. We
      examined predictors for the number of included components within each category
      using Poisson regression models. Predictors included work processes (document
      completion in relation to discharge day; completion time of day) and provider
      characteristics (training year; specialty). KEY RESULTS: Historical components
      (i.e., 'patient's medical course' category) were included more often than
      components that directly inform the admission orders in the sub-acute care
      facility (i.e., 'future plan of care'). In this latter category, most summaries
      included a discharge medication list (99%), disposition (90%), and instructions
      for follow-up (91%), but less frequently included diet (68%), activity
      instructions (58%), therapy orders (56%), prognosis/diagnosis communication to
      patient/family (15%), code status (7%), and pending studies (6%). 'Future plan of
      care' components were more likely to be omitted if a discharge summary was
      created >24 h after discharge (incident rate ratio = 0.91, 95% confidence
      interval = 0.84-0.98) or if an intern created the summary (0.90, 0.83-0.97).
      CONCLUSION: Critical component omissions in discharge summaries were common, and
      were associated with delayed document creation and less experienced providers.
      More research is needed to understand the impact of discharge documentation
      quality on patient/system outcomes.

PMID- 21901493
TI  - Outcomes, outcomes, every where, nor any stop to think?

PMID- 21901494
TI  - From the editors' desk: religion, health and cucumbers.

PMID- 21901495
TI  - Fostering educational innovation through measuring outcomes.

PMID- 21901497
TI  - A 7-year-old girl with subcutaneous emphysema, pneumomediastinum, pneumothorax,
      and pneumoretroperitoneum caused by Mycoplasma pneumoniae pneumonia.
AB  - A 7-year-old girl presented with subcutaneous emphysema, pneumomediastinum (PM),
      pneumoretroperitoneum, and pneumothorax caused by Mycoplasma pneumoniae (MP). The
      patient had been treated with clarithromycin for pneumonia at another hospital;
      however, her condition deteriorated and complications developed. Soon after
      admission to our hospital, we started the patient on minocycline and
      prednisolone, and the complications improved promptly. Laboratory data showed
      serum ferritin and urinary beta-2-microglobulin levels were greatly elevated. We
      therefore speculated that the patient might have underlying hypercytokinemia.
      Prednisolone is an effective treatment for hypercytokinemia. We therefore
      recommend prednisolone treatment for cases of severe M. pneumoniae pneumonia that
      do not respond to antimicrobial agents.

PMID- 21901498
TI  - Mechanism of drug interaction between a Kampo medicine, byakkokaninjinto, and
      tetracycline in rats.
AB  - We have previously reported that concomitant oral administration of the Kampo
      medicine, byakkokaninjinto (TJ-34), in extract granules, reduced the plasma
      concentrations of tetracycline (TC) and ciprofloxacin in humans, which might be
      the result of forming a chelate with Ca(2+). In the present study, we
      investigated the effect of a chelating agent, ethylenediaminetetraacetic acid
      (EDTA), on the plasma concentration-time profiles of TC after coadministration of
      TJ-34 dried extract and TC in rats to clarify whether metal ions contained in the
      TJ-34 dried extract contribute to this interaction. TJ-34 dried extract
      significantly reduced the plasma concentration of TC. The values of maximum
      concentration (C (max)), area under the plasma concentration-time curve and
      percentage of urinary recovery (f (e)) of TC were reduced to 42%, 40%, and 45%,
      respectively. On the other hand, treatment with EDTA significantly counteracted
      the effect of TJ-34 dried extract to reduce absorption of TC, indicating that
      metal ions mainly account for the interaction. Next, we investigated the effect
      of staggered administration of TJ-34 dried extract and TC to avoid the drug
      interaction between them. Administration of TJ-34 dried extract 2 h before TC had
      no effect on plasma concentrations and pharmacokinetic parameters of TC. These
      results provide a precise mechanism of the interaction TJ-34 and TC, suggesting a
      safe and effective dosage regimen to coadminister TJ-34 and TC in clinical use.

PMID- 21901496
TI  - Making connections: pathology and genetics link amyotrophic lateral sclerosis
      with frontotemporal lobe dementia.
AB  - Over the last couple of decades, there has been a growing body of clinical,
      genetic, and histopathological evidence that similar pathological processes
      underlie amyotrophic lateral sclerosis (ALS) and some types of frontotemporal
      lobe dementia (FTD). Even though there is great diversity in the genetic causes
      of these disorders, there is a high degree of overlap in their histopathology.
      Genes linked to rare cases of familial ALS and/or FTD, like FUS, TARDBP, OPTN,
      and UBQLN2 may converge onto a unifying pathogenic pathway and thereby provide
      novel therapeutic targets common to a spectrum of etiologically diverse forms of
      ALS and ALS-FTD. Additionally, there are major loci for ALS-FTD on chromosomes 9p
      and 15q. Identification of causative genetic alterations at those loci will be an
      important step in understanding the pathogenesis of juvenile- and adult-onset ALS
      and ALS-FTD. Interactions between TDP-43, FUS, optineurin, and ubiquilin 2 need
      to be studied to understand their common molecular pathways. Future efforts
      should also be directed towards generation and characterization of in vivo models
      to dissect the pathogenic mechanisms of these diseases. Such efforts will rapidly
      accelerate the discovery of new drugs that regulate accumulation of pathogenic
      proteins and their downstream consequences.

PMID- 21901499
TI  - A pre-visit tailored website enhances counselees' realistic expectations and
      knowledge and fulfils information needs for breast cancer genetic counselling.
AB  - Counselees who are the first in their family to request breast cancer genetic
      counselling often don't know what to expect or have unrealistic expectations of
      genetic counselling. Receiving tailored information might help them to prepare
      for their first visit. We conducted a study of the effects of a pre-visit website
      providing computer-tailored information (E-info gene(ca)), on counselees'
      expectations, knowledge about breast cancer and heredity and information needs.
      Counselees were randomized to receive usual care (UC) or UC plus website. All
      counselees completed a baseline questionnaire and those randomized to the
      intervention group also completed a questionnaire after having viewed the
      website. After having accessed E-info gene(ca) counselees (n = 101) better knew
      what to expect of their first visit (chi(2) = 4.43; P = .04) and less often
      showed unrealistic expectations about possibilities for DNA-testing (chi(2) =
      4.84; P = .03) than counselees in the UC group (n = 89). In addition, the website
      increased counselees' knowledge of breast cancer and heredity (B = .23; P = .003)
      and lowered their information needs (B = -.16; P = .000) compared to the UC
      group. Especially, information concerning procedural aspects and emotional
      consequences of genetic counselling was considered less important. This study
      showed that counselees know more and need less when they are provided with
      extended pre-visit information through a tailored website and counselees enter
      the visit with more realistic expectations of genetic counselling. This might
      facilitate and focus communication within the subsequent consultation.

PMID- 21901500
TI  - Two novel mutations in hMLH1 gene in Iranian hereditary non-polyposis colorectal
      cancer patients.
AB  - Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common
      forms of hereditary colorectal cancer. It is an autosomal dominant disorder
      resulting from germline mutations in DNA mismatch repair genes. In this study, we
      screened hMLH1 gene in a group of Iranian HNPCC patients using polymerase chain
      reaction-single strand conformational polymorphism and direct sequencing methods.
      Here we report two novel frameshift mutations in this gene in our studied
      population. One of them results from a deletion of "T" at codon 36, exon 1 which
      causes premature stop codon and a truncated protein. The other results from a
      deletion of "T" at codon 753, exon 19 causing a delayed stop codon. There are a
      variety of the reported novel mutations in hMLH1 gene studies. Identification of
      these mutations is necessary in different populations and can help the management
      of colorectal cancer in these populations by screening, by prevention strategies,
      and by following up the suspected HNPCC families.

PMID- 21901502
TI  - The pedunculopontine nucleus: from basic neuroscience to translational
      applications for Parkinson's disease.

PMID- 21901501
TI  - The effect of intrathecal administration of glial activation inhibitors on dorsal
      horn BDNF overexpression and hind paw mechanical allodynia in spinal nerve
      ligated rats.
AB  - Recent studies have suggested that activated glia in the spinal cord may play a
      vital role at different times during spinal nerve ligation (SNL)-induced
      neuropathic pain; therefore, glial activation inhibitors have been used as
      effective painkillers. Brain-derived neurotrophic factor (BDNF) is also known to
      be a powerful pain modulator, but it remains unclear how it contributes to the
      glial activation inhibitor-based treatment. This study revealed the following
      results: (1) intrathecal administration of minocycline (a microglial activation
      inhibitor) could prevent mechanical allodynia during the initiation of SNL
      induced neuropathic pain, and its action was associated with the elimination of
      BDNF overexpression in the dorsal horn; (2) the spinal injection of fluorocitrate
      (an astrocytic activation inhibitor) but not minocycline could reverse mechanical
      allodynia during the maintenance phase of SNL-induced pain, and its action was
      also related to a decrease in BDNF overexpression in the dorsal horn; and (3)
      treatment with TrkB/Fc (a BDNF-sequestering protein) had a similar effect during
      both the early development and maintenance periods. These results led to the
      following conclusions: (1) elevated BDNF expression in the dorsal horn was
      required to develop and maintain neuropathic pain; (2) minocycline could only
      prevent mechanical allodynia in the early stages, possibly by inhibiting BDNF
      release from microglia; and (3) fluorocitrate could reverse existing mechanical
      allodynia, and its action was associated with the inhibition of BDNF upregulation
      induced by astrocytic activation.

PMID- 21901503
TI  - Red cell exchange transfusion as a rescue therapy for tacrolimus toxicity in a
      paediatric renal transplant.
AB  - Tacrolimus is a widely used macrolide immunosuppressant that has a narrow
      therapeutic index and potential side effects including neurotoxicity. A 20-month
      old boy with kidney disease secondary to prune belly syndrome variant, managed on
      peritoneal dialysis, received a deceased donor transplant. Standard
      immunosuppression was used. There was good early graft function. Post-transplant
      he developed fungal peritonitis associated with a significant reduction in graft
      function and was treated with caspofungin and fluconazole. Despite tacrolimus
      dose reduction he developed a rapid rise in tacrolimus concentration to a maximum
      of 72 ng/ml with an otherwise unexplained reduction in consciousness. He
      underwent a single volume exchange transfusion with packed red cells and 4.5%
      albumin (ratio 2:1). This resulted in immediate reduction of his tacrolimus
      concentration from 61.8 ng/ml to 35.2 ng/ml. The neurological deficit rapidly
      resolved. The fungal peritonitis was eradicated. Renal function recovered from a
      nadir of eGFR <10 ml/min/1.73 m2 to a baseline of 30 ml/min/1.73 m2. At 30 months
      post-transplant the child has creatinine of 1.4 mg/dl (eGFR of 31 ml/min/1.73
      m2), and is developmentally appropriate with no neurological deficit. Red cell
      exchange transfusion is a potentially safe and effective way of managing severe
      and symptomatic tacrolimus toxicity.

PMID- 21901504
TI  - Recovery of strongylid third-stage larvae from herbage samples: standardisation
      of a laboratory method and its application in the field.
AB  - The estimation of parasitic nematode larvae present on pasture is an important
      tool applied in many epidemiological studies. In the face of climatic changes,
      there is increased interest in identifying parameters influencing the survival of
      free-living stages of parasites under different meteorological conditions. In
      order to predict possible risk factors for grazing livestock, reliable and
      reproducible methods to assess the density of larvae on pasture are required. A
      laboratory method for the recovery of strongylid third-stage larvae from herbage
      samples was developed, standardised and its efficacy assessed in controlled
      experiments as well as under field conditions. Grass samples free of any nematode
      larvae were used and inoculated with known numbers of third-stage larvae of
      Cooperia oncophora in different concentrations. The grass samples were inoculated
      with larvae over 24 h, followed by soaking for 4 h. The recovery process included
      washing over sieves and centrifugation of the obtained liquid. The total time
      required for the recovery process was about 5-7 h (excluding inoculation).
      Recovery rates range from 68% to 98% and a strong correlation between numbers of
      larvae added to the grass samples and numbers of larvae that could be recovered
      was observed (p < 0.001). The new method proved to be reproducible and provides
      high recovery rates combined with the potential to handle many samples
      simultaneously in a relatively short time, thus offering high throughput
      opportunities applicable to field experiments.

PMID- 21901505
TI  - Effect of gender difference on platelet reactivity.
AB  - BACKGROUND: Previous studies have suggested that women do not accrue equal
      therapeutic benefit from antiplatelet medication as compared with men. The
      physiological mechanism and clinical implications behind this gender disparity
      have yet to be established. METHODS: On-treatment platelet reactivity was
      determined in 717 men and 234 women on dual antiplatelet therapy, undergoing
      elective coronary stent implantation. Platelet function testing was performed
      using arachidonic acid and adenosine diphosphate-induced light transmittance
      aggregometry (LTA) and the VerifyNow P2Y12 and Aspirin assays. Also the incidence
      of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and
      ischaemic stroke was evaluated. RESULTS: Women had higher baseline platelet
      counts than men. Women exhibited a higher magnitude of on-aspirin platelet
      reactivity using LTA, but not using the VerifyNow Aspirin assay. The magnitude of
      on-clopidogrel platelet reactivity was significantly higher in women as compared
      with men with both tests used. The cut-off value to identify patients at risk as
      well as the incidence of clinical endpoints was similar between women and men
      (16/234[6.8%] vs. 62/717[8.6%], p = 0.38). CONCLUSION: Although the magnitude of
      platelet reactivity was higher in women, the absolute difference between genders
      was small and both the cut-off value to identify patients at risk and the
      incidence of the composite endpoint were similar between genders. Thus, it is
      unlikely that the difference in platelet reactivity accounts for a worse
      prognosis in women.

PMID- 21901506
TI  - Pre-pregnancy risk assessment and counselling of the cardiac patient.
AB  - Pregnant women with heart disease often have an increased risk of maternal
      cardiovascular and offspring complications. The magnitude of these risks varies
      depending on the type and severity of the underlying disease. Therefore risk
      assessment should be performed before pregnancy. This can be accomplished by
      taking into account predictors and risk scores that have been developed in large
      populations of pregnant women with heart disease, as well as by consulting
      disease-specific pregnancy literature. A system that integrates all available
      knowledge about the risk of pregnancy is the adapted World Health Organisation
      risk classification. The safety of pregnancy for women with heart disease can be
      enhanced by adequate risk assessment and counselling.

PMID- 21901507
TI  - Rights, knowledge, and governance for improved health equity in urban settings.
AB  - All three of the interacting aspects of daily urban life (physical environment,
      social conditions, and the added pressure of climate change) that affect health
      inequities are nested within the concept of urban governance, which has the task
      of understanding and managing the interactions among these different factors so
      that all three can be improved together and coherently. Governance is defined as:
      "the process of collective decision making and processes by which decisions are
      implemented or not implemented": it is concerned with the distribution, exercise,
      and consequences of power. Although there appears to be general agreement that
      the quality of governance is important for development, much less agreement
      appears to exist on what the concept really implies and how it should be used.
      Our review of the literature confirmed significant variation in meaning as well
      as in the practice of urban governance arrangements. The review found that the
      linkage between governance practices and health equity is under-researched and/or
      has been neglected. Reconnecting the fields of urban planning, social sciences,
      and public health are essential "not only for improving local governance, but
      also for understanding and addressing global political change" for enhanced urban
      health equity. Social mobilization, empowering governance, and improved knowledge
      for sustainable and equitable development in urban settings is urgently needed. A
      set of strategic research questions are suggested.

PMID- 21901508
TI  - [Annual Report 2009 of the German Cardiac Pacemaker Registry: Federal Section
      pacemaker and AQUA - Institute for Applied Quality Improvement and Research in
      Health Ltd].

PMID- 21901509
TI  - Neuroprotective effect of crocin on acrylamide-induced cytotoxicity in PC12
      cells.
AB  - Acrylamide (ACR) is a potent neurotoxic in human and animal models. In this
      study, the effect of crocin, main constituent of Crocus sativus L. (Saffron) on
      ACR-induced cytotoxicity was evaluated using PC12 cells as a suitable in vitro
      model. The exposure of PC12 cells to ACR reduced cell viability, increased DNA
      fragmented cells and phosphatidylserine exposure, and elevated Bax/Bcl-2 ratio.
      Results showed that ACR increased intracellular reactive oxygen species (ROS) in
      cells and ROS played an important role in ACR cytotoxicity. The pretreatment of
      cells with 10-50 MUM crocin before ACR treatment significantly attenuated ACR
      cytotoxicity in a dose-dependent manner. Crocin inhibited the downregulation of
      Bcl-2 and the upregulation of Bax and decreased apoptosis in treated cells. Also,
      crocin inhibited ROS generation in cells exposed to ACR. In conclusion, our
      results indicated that pretreatment with crocin protected cells from ACR-induced
      apoptosis partly by inhibition of intracellular ROS production.

PMID- 21901510
TI  - Aging-associated modulation in the expression of Pax6 in mouse brain.
AB  - Symptoms like mental retardation, depression, and anxiety have been observed
      during aging. Almost similar phenotypes have been evident in patients having
      haploinsufficiency or mutations in Pax6, a transcriptional regulator. Since Pax6
      regulates axon guidance, differentiation of neurons from glia, and neuronal
      migration, it has been considered as a marker of newly generated neurons. The
      immunohistochemical analysis of Pax6 positive cells and expression pattern of
      Pax6 in olfactory lobe, hippocampus, and cerebellum of aging mouse brain have
      been investigated. The number of Pax6 positive cells and level of Pax6 were
      reduced progressively in olfactory lobe, cerebellum, and hippocampus from
      postnatal day-zero (P0) to old age mice. Pax6 positive cells were significantly
      lower in dentate gyrus, CA1, CA2, and CA3 regions of hippocampus, in mitral cell
      (MiCe), and internal plexiform (InPl) layers of olfactory lobe, and in granular
      cell (GrLa), and Purkinje's cell (PuCe) layers of cerebellum from P0 to old age.
      Thus, modulation in the expression of Pax6 and reduction in Pax6 positive cells
      show direct association of Pax6 with aging-related neuronal dystrophy.

PMID- 21901511
TI  - Supplementation of DHA-rich microalgal oil or fish oil during the suckling period
      in mildly n-3 fatty acid-deficient rat pups.
AB  - Long-chain polyunsaturated fatty acids (LC-PUFA), particularly arachidonic acid
      (ARA) and docosahexaenoic acid (DHA), are considered critical for the development
      of infants and are commonly supplemented in infant formulae. In this study, two
      common sources of n-3 LC-PUFA, fish oil (FO) and DHA-rich microalgal oil (DMO),
      were fed to rat pups of mildly n-3 PUFA-deficient dams to compare changes in LC
      PUFA of tissue phospholipids. The milk from dams fed a n-3 PUFA-deficient diet
      contained less n-3 LC-PUFA than that of dams fed a control diet (AIN-93G). The
      pups' were given orally 1 mg/g weight of either FO or DMO for 17 days between the
      ages of 5 and 21 days, the pups were weaned, and sacrificed 1 week later for
      analysis of fatty acid compositions of brain, heart, kidney, spleen, and thymus
      phospholipids. Although both FO and DMO brought about a recovery in the tissue
      DHA levels compared to those of the control group (pups from AIN-93G-fed dams),
      DMO was more effective at restoring tissue LC-PUFA status because it was richer
      in DHA than FO. FO had a slightly lower PUFA level than that required to bring
      the LC-PUFA status completely to normal levels in this experiment, and EPA did
      not accumulate in tissues under the conditions tested here. These results
      demonstrate the effectiveness of ingesting either FO or DMO in the pre-weaning
      period for improving mild n-3 PUFA deficiency.

PMID- 21901512
TI  - Emotional cues enhance the attentional effects on spatial and temporal
      resolution.
AB  - In the present study, we demonstrated that the emotional significance of a
      spatial cue enhances the effect of covert attention on spatial and temporal
      resolution (i.e., our ability to discriminate small spatial details and fast
      temporal flicker). Our results indicated that fearful face cues, as compared with
      neutral face cues, enhanced the attentional benefits in spatial resolution but
      also enhanced the attentional deficits in temporal resolution. Furthermore, we
      observed that the overall magnitudes of individuals' attentional effects
      correlated strongly with the magnitude of the emotion * attention interaction
      effect. Combined, these findings provide strong support for the idea that emotion
      enhances the strength of a cue's attentional response.

PMID- 21901513
TI  - Motion onset does not capture attention when subsequent motion is "smooth".
AB  - Previous research on the attentional effects of moving objects has shown that
      motion per se does not capture attention. However, in later studies it was argued
      that the onset of motion does capture attention. Here, we show that this motion
      onset effect critically depends on motion jerkiness--that is, the rate at which
      the moving stimulus is refreshed. Experiment 1 used search displays with a
      static, a motion-onset, and an abrupt-onset stimulus, while systematically
      varying the refresh rate of the moving stimulus. The results showed that motion
      onset only captures attention when subsequent motion is jerky (8 and 17 Hz), not
      when it is smooth (33 and 100 Hz). Experiment 2 replaced motion onset with
      continuous motion, showing that motion jerkiness does not affect how continuous
      motion is processed. These findings do not support accounts that assume a special
      role for motion onset, but they are in line with the more general unique-event
      account.

PMID- 21901516
TI  - Ultrastructural and mineral phase characterization of the bone-like matrix
      assembled in F-OST osteoblast cultures.
AB  - Cell cultures are often used to study bone mineralization; however, not all
      systems achieve a bone-like matrix formation. In this study, the mineralized
      matrix assembled in F-OST osteoblast cultures was analyzed, with the aim of
      establishing a novel model for bone mineralization. The ultrastructure of the
      cultures was investigated using scanning electron microscopy, atomic force
      microscopy, and transmission electron microscopy (TEM). The mineral phase was
      characterized using conventional and high-resolution TEM, energy-dispersive X-ray
      spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, and
      solid-state (31)P and (1)H nuclear magnetic resonance. F-OST osteoblast cultures
      presented a clear nodular mineralization pattern. The chief features of the
      mineralizing nodules were globular accretions ranging from about 100 nm to 1.5
      MUm in diameter, loaded with needle-shaped crystallites. Accretions seemed to bud
      from the cell membrane, increase in size, and coalesce into larger ones. Arrays
      of loosely packed, randomly oriented collagen fibrils were seen along with the
      accretions. Mineralized fibrils were often observed, sometimes in close
      association with accretions. The mineral phase was characterized as a poorly
      crystalline hydroxyapatite. The Ca/P atomic ratio was 1.49 +/- 0.06. The presence
      of OH was evident. The lattice parameters were a = 9.435 A and c = 6.860 A. The
      average crystallite size was 20 nm long and 10 nm wide. Carbonate substitutions
      were seen in phosphate and OH sites. Water was also found within the apatitic
      core. In conclusion, F-OST osteoblast cultures produce a bone-like matrix and may
      provide a good model for bone mineralization studies.

PMID- 21901517
TI  - Laparoscopic low anterior resection for early rectal cancer.
AB  - INTRODUCTION: Early rectal cancer (ERC) is adenocarcinoma that has invaded into,
      but not extended beyond, the submucosa. Endoscopic or minimal access surgical
      procedures, such as laparoscopic resection, have emerged as a useful tool in the
      surgical treatment of such diseases. The aim of this study is to present and
      analyze the feasibility, the short- and long-term results of laparoscopic
      colorectal surgery (LCS) in patients with ERC. PATIENTS AND METHODS: Between 2002
      and 4/2011, a total of 164 patients with colorectal cancer underwent laparoscopic
      surgery (LS). Of these, 7 patients (4.2%) had ERC and underwent laparoscopic
      anterior resection (LAR). The median follow-up was 41 months. RESULTS: The mean
      operative time was 2.5 h. None of the laparoscopic procedures was converted to
      open surgery. Liquids and solid food were started on median postoperative days 1
      and 3, respectively. The median length of postoperative stay was 5 days.
      Postoperative complications occurred in 2 patients (28.5%), including wound
      infection in one patient (14.2%) and atelectasis in one patient (14.2%). None of
      the patients required an urgent re-operation. There was no mortality related to
      LS. CONCLUSIONS: LS for ERC can be used as a strategy sited between endoscopic
      mucosal resection and open anterior resection with beneficial long- and short
      term results. It appears as a technically and oncologically safe procedure when
      performed by surgeons with sufficient experience in laparoscopic techniques.

PMID- 21901518
TI  - Mechanical bowel preparation before elective colorectal surgery: is it necessary?
AB  - AIM: To present the worldwide accepted guidelines concerning the use of
      mechanical bowel preparation (MBP) before elective colorectal surgery (ECS).
      PATIENTS AND METHODS: We conducted a retrospective review of the Pubmed Databases
      for randomized controlled trials (RCTs) and meta-analyses, which included adult
      patients who underwent elective colorectal surgery. We compared the patients who
      had a preoperative MBP with those who did not. Significant factors that were
      taken into account were postoperative septic complications and anastomotic
      dehiscence. RESULTS: Our search revealed 5 RCTs and 2 meta-analyses that met our
      criteria. Patients who underwent emergency colorectal surgery were excluded from
      the study. We identified the recommendations for 6 different types of elective
      colorectal surgery. CONCLUSION: MBP has been for many years a standard clinical
      procedure for patients undergoing elective colorectal surgery. However, many
      recent researches suggest the omission of MBP, since there are no significant
      differences regarding postoperative infectious complications, such as anastomotic
      dehiscence and superficial surgical site infections. Furthermore, MBP is a time
      consuming, expensive procedure and causes severe discomfort to the patient. More
      importantly, the application of MBP has been associated with serious
      complications in both healthy patients and patients with existing cardiac or
      renal disease, such as electrolyte and volume disturbances.

PMID- 21901519
TI  - Alterations in colonic transit time after laparoscopic versus open
      cholecystectomy: a clinical study.
AB  - PURPOSE: Postoperative enteral paresis constitutes a common problem for surgeons
      around the world. Evidence by many authors suggests that colonic inertia
      constitutes a major component of postoperative enteral paresis. This study aims
      at comparing the effect of laparoscopic versus open cholecystectomy on colonic
      transit time in humans. MATERIALS AND METHODS: In this study, were included a
      total of 29 patients suffering from cholelithiasis, divided into two groups, a
      laparoscopic cholecystectomy and an open cholecystectomy group. All patients
      ingested one capsule containing 24 radiopaque markers on the day of the
      operation, and plain abdominal films were obtained on the 3rd postoperative day.
      The number of remaining markers was counted, and the percentage of rejected
      markers was calculated. For the statistical analysis, SPSS for windows version 12
      was used. RESULTS AND DISCUSSION: The study's results show a significant
      difference in postoperative colonic motility, in favor of the laparoscopic
      cholecystectomy group (P = 0,001). Causative interpretation of these results is
      difficult, mainly due to the multifactorial nature of postoperative colonic
      hypomotility. CONCLUSION: The present study suggests an advantage of laparoscopic
      cholecystectomy, as far as the duration of postoperative colonic paresis is
      concerned.

PMID- 21901520
TI  - Emergency and elective surgery for small bowel Crohn's disease.
AB  - Advancements in the medical treatment of Crohn's disease have reduced the need
      for surgery. The indications for surgery include the failure of medical
      management, especially the persistence or worsening of symptoms in spite of
      proper treatment and complications of the disease process. These complications
      include intestinal obstruction, intestinal perforation with fistula formation or
      abscess, free perforation, gastrointestinal bleeding, urologic complications,
      cancer, and perianal disease. In these cases, operative therapy should be
      directed to the specific indication for surgery, resecting only the segment of
      bowel involved in the complicating process while preserving as much bowel length
      as possible in order to prevent short-bowel syndrome. Laparoscopic surgery has
      been gaining acceptance as an alternative surgical approach for properly selected
      patients with Crohn's disease. In conclusion, identifying the need for surgery
      and determining the timing of operation are the cornerstones to successful
      surgical management of patients with Crohn's disease.

PMID- 21901521
TI  - Insight from the draft genome of Dietzia cinnamea P4 reveals mechanisms of
      survival in complex tropical soil habitats and biotechnology potential.
AB  - The draft genome of Dietzia cinnamea strain P4 was determined using
      pyrosequencing. In total, 428 supercontigs were obtained and analyzed. We here
      describe and interpret the main features of the draft genome. The genome
      contained a total of 3,555,295 bp, arranged in a single replicon with an average
      G+C percentage of 70.9%. It revealed the presence of complete pathways for
      basically all central metabolic routes. Also present were complete sets of genes
      for the glyoxalate and reductive carboxylate cycles. Autotrophic growth was
      suggested to occur by the presence of genes for aerobic CO oxidation,
      formate/formaldehyde oxidation, the reverse tricarboxylic acid cycle and the 3
      hydropropionate cycle for CO(2) fixation. Secondary metabolism was evidenced by
      the presence of genes for the biosynthesis of terpene compounds, frenolicin,
      nanaomycin and avilamycin A antibiotics. Furthermore, a probable role in
      azinomycin B synthesis, an important product with antitumor activity, was
      indicated. The complete alk operon for the degradation of n-alkanes was found to
      be present, as were clusters of genes for biphenyl ring dihydroxylation. This
      study brings new insights in the genetics and physiology of D. cinnamea P4, which
      is useful in biotechnology and bioremediation.

PMID- 21901522
TI  - Diffuse periventricular leukomalacia in preterm children: assessment of grey
      matter changes by MRI.
AB  - BACKGROUND: Preterm children may have cognitive deficits and behavioural
      disorders suggestive of grey matter (GM) injury. The prevalence is higher in
      preterm children with diffuse periventricular leukomalacia (dPVL). OBJECTIVE:
      Evaluate changes in the volume of 116 GM areas in preterm children with dPVL.
      METHODS AND MATERIALS: Eleven preterm children with dPVL, gestational age 32.8 +/
      2.6 weeks, examined at corrected age 22.0 +/- 18.2 months and 33 matched preterm
      controls with normal brain MRI were studied. Volumes of 116 individual GM areas,
      and white matter/cerebrospinal fluid (WM/CSF) ratio were calculated on T1
      weighted high-resolution images after segmentation. RESULTS: Relative to
      controls, children with dPVL had decreased GM volume of the hippocampus,
      amygdala, and frontal lobes and temporal middle gyrus (P < 0.05); increased GM
      volume of the putamen, thalamus, globus pallidum, superior temporal gyrus and of
      the parietal and occipital lobes (P < 0.05) and lower WM volume/higher CSF volume
      (P < 0.05). WM/CSF ratios also differed (P < 0.05). CONCLUSIONS: Preterm children
      with dPVL have increased regional GM volume in some areas probably related with a
      process of brain plasticity-regeneration and reduced GM volume in areas
      associated with cognition and memory.

PMID- 21901523
TI  - Regional cerebellar volumes predict functional outcome in children with
      cerebellar malformations.
AB  - The cerebellum has recently been recognized for its role in high-order functions,
      including cognition, language, and behavior. Recent studies have also begun to
      describe a functional topography of the mature cerebellum that includes
      organization on a mediolateral axis. However, no study to date has examined the
      relationship between regional cerebellar volume and developmental disabilities in
      children with cerebellar malformations. The objective of this study was to
      estimate the extent to which total and regional cerebellar volumes are associated
      with developmental disabilities in a cohort of children with cerebellar
      malformations. Children aged 1 to 6 years with a diagnosis of cerebellar
      malformation underwent standardized outcome measures and quantitative magnetic
      resonance scanning. The cerebellum was parcellated into seven mediolateral zones
      (three for each hemisphere plus the vermis) for regional volume analysis. In
      children with cerebellar malformations, decreased total cerebellar volume was
      associated with delays in global development, expressive language, cognition, as
      well as gross and fine motor function. Decreased volume in the right lateral
      cerebellar hemisphere was related to impaired cognition, expressive language, and
      gross motor function. Additionally, reduced vermis volume was associated with
      impaired global development, cognition, expressive language, and gross and fine
      motor skills, as well as behavior problems and a higher rate of positive autism
      spectrum screening test. These results begin to define the structural topography
      of functional outcome in children with cerebellar malformations and should lead
      to greater accuracy of prognostication as well as timely early developmental
      interventions.

PMID- 21901524
TI  - Knockdown of Mad2 induces osteosarcoma cell apoptosis-involved Rad21 cleavage.
AB  - BACKGROUND: Besides Mad2's role in carcinogenesis, recent study has shown that it
      is essential in cell survival. Here we found that knockdown of Mad2 causes
      osteosarcoma cell death through apoptosis, with the apoptotic signal resulting
      from Rad21 cleavage. METHODS: U2OS and MG63 cells were divided into three groups:
      the Mad2 siRNA group, mock group and normal control group; the Mad2 siRNA group
      and mock group are transfected with Mad2 shRNA plasmid and mock plasmid,
      respectively. G418 was used to increase the transfection efficacy, which was
      evaluated by GFP fluorescence. Quantitative PCR and Western blotting analyses
      were used to detect the transcription and expression of Mad2, Rad21 and caspase
      3, respectively. Flow cytometry assay using PE-labeled Annexin-V and PI, TUNEL
      assay and Hoechst 33258 staining were used to evaluate cell apoptosis. RESULTS:
      We successfully achieved knockdown of Mad2 expression in cancer cells using RNA
      interference. We observed obvious apoptosis in the Mad2 siRNA group compared with
      the Mock and control group. We found that the apoptosis induced by Mad2 knockdown
      correlated with Rad21 cleavage. CONCLUSION: These results confirmed that
      knockdown of Mad2 causes osteosarcoma cell death through apoptosis and provides
      evidence that the apoptotic signal resulted from Rad21 cleavage. This study
      suggested that Mad2 has potential to be a novel target for cancer therapy.

PMID- 21901525
TI  - Changes in pelvic tilt following total hip arthroplasty.
AB  - BACKGROUND: It is important to understand chronological changes in pelvic tilt
      after total hip arthroplasty (THA). In this study, we first investigated changes
      in pelvic tilt after THA. Second, we determined the correlation between
      preoperative pelvic tilt and the extent of postoperative changes in the pelvic
      tilt. Third, we evaluated the effects of changes in pelvic tilt on postoperative
      function and disability. METHODS: We examined 149 patients who received primary
      THA over a follow-up period of 1 year. We compared postoperative changes with the
      preoperative pelvic tilt on the basis of the anterior pelvic plane (APP) defined
      by DiGioia and patient demographics. RESULTS: A significant correlation was
      observed between preoperative APP and the amount of postoperative change in APP,
      suggesting that patients with severe preoperative pelvic tilt generally
      experience greater postoperative changes in pelvic tilt. Our data showed that
      patients with preoperative anterior pelvic tilt generally exhibit posterior
      changes in pelvic tilt after operation, while patients with preoperative
      posterior pelvic tilts did not experience significant postoperative changes in
      pelvic tilt. The 1-year postoperative function scores in patients with
      preoperative anterior pelvic tilt were lower than those in patients with
      preoperative posterior pelvic tilt. CONCLUSIONS: Pelvic tilt changed by varying
      degrees following THA. Special attention must be paid when positioning the
      acetabular component, particularly in patients with severe pelvic tilt prior to
      surgery. A greater understanding of the postoperative changes in pelvic tilt may
      improve the outcome of THA.

PMID- 21901526
TI  - Translational research on the mitral valve: from developmental mechanisms to new
      therapies.

PMID- 21901527
TI  - Phenotype switching and mutations in random environments.
AB  - Cell populations can benefit from changing phenotype when the environment
      changes. One mechanism for generating these changes is stochastic phenotype
      switching, whereby cells switch stochastically from one phenotype to another
      according to genetically determined rates, irrespective of the current
      environment, with the matching of phenotype to environment then determined by
      selective pressure. This mechanism has been observed in numerous contexts, but
      identifying the precise connection between switching rates and environmental
      changes remains an open problem. Here, we introduce a simple model to study the
      evolution of phenotype switching in a finite population subject to random
      environmental shocks. We compare the successes of competing genotypes with
      different switching rates, and analyze how the optimal switching rates depend on
      the frequency of environmental changes. If environmental changes are as rare as
      mutations, then the optimal switching rates mimic the rates of environmental
      changes. If the environment changes more frequently, then the optimal genotype
      either maximally favors fitness in the more common environment or has the maximal
      switching rate to each phenotype. Our results also explain why the optimum is
      relatively insensitive to fitness in each environment.

PMID- 21901528
TI  - Phosphorylation and nitration levels of photosynthetic proteins are conversely
      regulated by light stress.
AB  - Using a label-free mass spectrometric approach, we investigated light-induced
      changes in the distribution of phosphorylated and nitrated proteins within
      subpopulations of native photosynthetic complexes in the thylakoid membrane of
      Arabidopsis thaliana leaves adapted to growth light (GL) and subsequently exposed
      to high light (HL). Eight protein phosphorylation sites were identified in
      photosystem II (PSII) and the phosphorylation level of seven was regulated by HL
      as determined based on peak areas from ion chromatograms of phosphorylated and
      non-phosphorylated peptides. Although the phosphorylation of PSII proteins was
      reported in the past, we demonstrated for the first time that two minor antenna
      LHCB4 isoforms are alternately phosphorylated under GL and HL conditions in PSII
      monomers, dimers and supercomplexes. A role of LHCB4 phosphorylation in state
      transition and monomerization of PSII under HL conditions is proposed. We
      determined changes in the nitration level of 23 tyrosine residues in five
      photosystem I (PSI) and nine PSII proteins and demonstrated for the majority of
      them a lower nitration level in PSI and PSII complexes and supercomplexes under
      HL conditions, as compared to GL. In contrast, the nitration level significantly
      increased in assembled/disassembled PSI and PSII subcomplexes under HL
      conditions. A possible role of nitration in (1) monomerization of LHCB1-3 trimers
      under HL conditions (2) binding properties of ferredoxin-NADP+ oxidoreductase to
      photosystem I, and (3) PSII photodamage and repair cycle, is discussed. Based on
      these data, we propose that the conversely regulated phosphorylation and
      nitration levels regulate the stability and turnover of photosynthetic complexes
      under HL conditions.

PMID- 21901529
TI  - [Dimensions and interpretative patterns of aging: attitudes about aging, being
      old and ways of living in old age].
AB  - Attitudes about older people and being old develop in the early and middle phases
      of life and influence the subsequent aging process. Because aging processes vary
      across different domains of life and functioning, one cannot assume unanimously
      negative or positive attitudes towards old age and aging. Thus, in the
      psychological part of the project Zones of Transition ("Zonen des Ubergangs"),
      age stereotypes and views of the self in old age were assessed in different life
      domains and for different age groups, and their relation to well-being and the
      self-concept was investigated. The project also focused on the analysis of
      attitudes towards one's personal way of living in old age. A questionnaire was
      developed that assesses those attitudes on the basis of the dimensions "active
      commitment" and "pleasure and leisure". Our results support a multidimensional
      conception of attitudes towards aging and way of living in old age as well as of
      their influence on development across the lifespan.

PMID- 21901531
TI  - Glutamate dehydrogenase requirement for apoptosis induced by aristolochic acid in
      renal tubular epithelial cells.
AB  - Ingestion of aristolochic acids (AA) contained in herbal remedies results in a
      renal disease and, frequently, urothelial malignancy. The genotoxicity of AA in
      renal cells, including mutagenic DNA adduct formation, is well-documented.
      However, the mechanisms of AA-induced tubular atrophy and renal fibrosis are
      largely unknown. Epithelial cell death is a critical characteristic of these
      pathological conditions. To elucidate the mechanisms of AA-induced cytotoxicity,
      we explored AA-interacting proteins in tubular epithelial cells (TEC). We found
      that AA interacts with a mitochondrial enzyme glutamate dehydrogenase (GDH) and
      moderately inhibits its activity. We report that AA induces cell death in GDH
      knockdown TEC preferentially via non-apoptotic means, whereas in GDH-positive
      cells, death was executed by both the non-apoptotic and apoptotic mechanisms.
      Apoptosis is an energy-reliant process and demands higher adenosine 5'
      triphosphate (ATP) consumption than does the non-apoptotic cell death. We found
      that, after AAI treatment, the ATP depletion is more pronounced in GDH-knockdown
      cells. When we reduced ATP in TEC cells by inhibition of glycolysis and
      mitochondrial respiration, cell death mode switched from apoptosis and necrosis
      to necrosis only. In addition, in cells incubated at low glucose and no glutamine
      conditions, oxaloacetate and pyruvate reduced AAI-induced apoptosis our data
      suggest that AAI-GDH interactions in TEC are critical for the induction of
      apoptosis by direct inhibition of GDH activity. AA binding may also induce
      changes in GDH conformation and promote interactions with other molecules or
      impair signaling by GDH metabolic products, leading to apoptosis.

PMID- 21901530
TI  - Carcinoembryonic antigen (CEA) and its receptor hnRNP M are mediators of
      metastasis and the inflammatory response in the liver.
AB  - This article discusses the role of carcinoembryonic antigen (CEA) as a
      facilitator of the inflammatory response and its effect on colorectal cancer
      hepatic metastasis. Colorectal cancer accounts for 11% of all cancers in the
      United States and the majority of deaths are associated with liver metastasis. If
      left untreated, median survival is only six to 12 months. Resection of liver
      metastases offers the only chance for cure. Of the small number of patients who
      have operable cancer most will have further tumor recurrence. The molecular
      mechanisms associated with colorectal cancer metastasis to the liver are largely
      unknown. However CEA production has been shown both clinically and experimentally
      to be a factor in an increased metastatic potential of colorectal cancers to the
      liver. CEA also has a role in protecting tumor cells from the effects of anoikis
      and this affords a selective advantage for tumor cell survival in the
      circulation. CEA acts in the liver through its interaction with its receptor
      (CEAR), a protein that is related to the hnRNP M family of RNA binding proteins.
      In the liver CEA binds with hnRNP M on Kupffer cells and causes activation and
      production of pro- and anti-inflammatory cytokines including IL-1, IL-10, IL-6
      and TNF-alpha. These cytokines affect the up-regulation of adhesion molecules on
      the hepatic sinusoidal endothelium and protect the tumor cells against
      cytotoxicity by nitric oxide (NO) and other reactive oxygen radicals. HnRNP M
      signaling in Kupffer cells appears to be controlled by beta-adrenergic receptor
      activation. The cells will respond to the beta-adrenergic receptor agonist
      terbutaline resulting in reduced TNF-alpha and increased IL-10 and IL-6
      production following CEA activation. This has implications for the control of
      tumor cell implantation and survival in the liver.

PMID- 21901532
TI  - Review: milk fat globule-EGF factor 8 expression, function and plausible signal
      transduction in resolving inflammation.
AB  - Although the cloning and molecular characterization of MFG-E8 was first reported
      in the early 90s, breakthrough on MFG-E8 research came into light when it was
      explored as an outstanding factor for phagocytosis of apoptotic cells by
      professional macrophages in 2002. Since then numerous studies have been performed
      on MFG-E8 not only to demonstrate the role of phagocytic clearance of apoptotic
      cells, but also to focus on a wide range of aspects, even emphasizing on a direct
      link to innate-immune systems. In terms of its role as therapeutic potentials,
      our group, as well as others, has shown MFG-E8 to be an essential factor in
      attenuating inflammation and improving prognosis in several animal models of life
      threatening diseases. Considering these versatile functions of MFG-E8, several in
      vitro and in vivo studies were embarked on to explore the mechanistic pathways
      exerted by MFG-E8 during inflammation. With the relevant cumulative findings,
      herein we reviewed the potential roles of MFG-E8 in pathophysiological conditions
      by highlighting its plausible signal-transduction mechanisms.

PMID- 21901533
TI  - Improving patient flow in an obstetric unit.
AB  - Hospitals have become increasingly interested in maximizing patient throughput
      and bed utilization in all units to improve efficiency. To study tradeoffs in
      blocking and system efficiency, a simulation model using a path-based approach is
      developed for an obstetric unit. The model focuses on patient flow, considering
      patient classification, blocking effects, time dependent arrival and departure
      patterns, and statistically supported distributions for length of stay (LOS). The
      model is applied to DeKalb Medical's Women's Center, a large obstetrics hospital
      in Atlanta, GA, to analyze the hospital's readiness for potential changes to
      patient mix and patient volume. A comparison of results predicted by the
      simulation model and actual performance after implementation of "swing" rooms is
      presented, suggesting the value of implementing "swing" rooms to balance bed
      allocation.

PMID- 21901535
TI  - Detection of neovascularization in diabetic retinopathy.
AB  - Diabetic retinopathy has become an increasingly important cause of blindness.
      Nevertheless, vision loss can be prevented from early detection of diabetic
      retinopathy and monitor with regular examination. Common automatic detection of
      retinal abnormalities is for microaneurysms, hemorrhages, hard exudates, and
      cotton wool spot. However, there is a worse case of retinal abnormality, but not
      much research was done to detect it. It is neovascularization where new blood
      vessels grow due to extensive lack of oxygen in the retinal capillaries. This
      paper shows that various combination of techniques such as image normalization,
      compactness classifier, morphology-based operator, Gaussian filtering, and
      thresholding techniques were used in developing of neovascularization detection.
      A function matrix box was added in order to classify the neovascularization from
      natural blood vessel. A region-based neovascularization classification was
      attempted as a diagnostic accuracy. The developed method was tested on images
      from different database sources with varying quality and image resolution. It
      shows that specificity and sensitivity results were 89.4% and 63.9%,
      respectively. The proposed approach yield encouraging results for future
      development.

PMID- 21901534
TI  - Monitoring antivascular therapy in head and neck cancer xenografts using contrast
      enhanced MR and US imaging.
AB  - BACKGROUND: The overall goal of this study was to non-invasively monitor changes
      in blood flow of squamous cell carcinoma of the head and neck (SCCHN) xenografts
      using contrast-enhanced magnetic resonance (MR) and ultrasound (US) imaging.
      METHODS: Experimental studies were performed on mice bearing FaDu tumors and
      SCCHN xenografts derived from human surgical tissue. MR examinations were
      performed using gadofosveset trisodium at 4.7T. Change in T1-relaxation rate of
      tumors (DeltaR1) and tumor enhancement parameters (amplitude, area under the
      curve-AUC) were measured at baseline and 24 h after treatment with a tumor
      vascular disrupting agent (tumor-VDA), 5,6-dimethylxanthenone-4-acetic acid
      (DMXAA; ASA404) and correlated with tumor necrosis and treatment outcome. CE-US
      was performed using microbubbles (Vevo MicroMarker(r)) to assess the change in
      relative tumor blood volume following VDA treatment. RESULTS: A marked decrease
      (up to 68% of baseline) in T1-enhancement of FaDu tumors was observed 1 day after
      VDA therapy indicative of a reduction in blood flow. Early (24 h) vascular
      response of individual tumors to VDA therapy detected by MRI correlated with
      tumor necrosis and volume estimates at 10 days post treatment. VDA treatment also
      resulted in a significant reduction in AUC and amplitude of patient tumor-derived
      SCCHN xenografts. Consistent with MRI observations, CE-US revealed a significant
      reduction in tumor blood volume of patient tumor-derived SCCHN xenografts after
      VDA therapy. Treatment with VDA resulted in a significant tumor growth inhibition
      of patient tumor derived SCCHN xenografts. CONCLUSIONS: These findings
      demonstrate that both CE-MRI and CE-US allow monitoring of early changes in
      vascular function following VDA therapy. The results also demonstrate, for the
      first time, potent vascular disruptive and antitumor activity of DMXAA against
      patient tumor-derived head and neck carcinoma xenografts.

PMID- 21901536
TI  - Evaluation of texture for classification of abdominal aortic aneurysm after
      endovascular repair.
AB  - The use of the endovascular prostheses in abdominal aortic aneurysm has proven to
      be an effective technique to reduce the pressure and rupture risk of aneurysm.
      Nevertheless, in a long-term perspective, complications such as leaks inside the
      aneurysm sac (endoleaks) could appear causing a pressure elevation and increasing
      the danger of rupture consequently. At present, computed tomographic angiography
      (CTA) is the most common examination for medical surveillance. However, endoleak
      complications cannot always be detected by visual inspection on CTA scans. The
      investigation on new techniques to detect endoleaks and analyse their effects on
      treatment evolution is of great importance for endovascular aneurysm repair
      (EVAR) technique. The purpose of this work was to evaluate the capability of
      texture features obtained from the aneurysmatic thrombus CT images to
      discriminate different types of evolutions caused by endoleaks. The regions of
      interest (ROIs) from patients with different post-EVAR evolution were extracted
      by experienced radiologists. Three techniques were applied to each ROI to obtain
      texture parameters, namely the grey level co-occurrence matrix (GLCM), the grey
      level run length matrix (GLRLM) and the grey level difference method (GLDM). The
      results showed that GLCM, GLRLM and GLDM features presented a good discrimination
      ability to differentiate between favourable or unfavourable evolutions. GLCM was
      the most efficient in terms of classification accuracy (93.41% +/- 0.024)
      followed by GLRLM (90.17% +/- 0.077) and finally by GLDM (81.98% +/- 0.045).
      According to the results, we can consider texture analysis as complementary
      information to classified abdominal aneurysm evolution after EVAR.

PMID- 21901537
TI  - From the editor's desk.

PMID- 21901538
TI  - Effect of RNAi-induced down regulation of nuclear factor kappa-B p65 on acute
      monocytic leukemia THP-1 cells in vitro and vivo.
AB  - NF-kappaB p65 is found constitutively active in acute monocytic leukemia, and has
      been considered an important factor for poor prognosis. Therefore, develop
      specifically target p65 inhibitors will be substantial interest. Until now,
      although several p65 inhibitors are currently in preclinical and clinical
      development, none of them are targeting. In this study, siRNA targeting p65 was
      introduced into the acute monocytic leukemia cell line THP-1 and THP-1 xenograft
      tumors in nude mice, and then, we measured p65 mRNA and protein levels by real
      time RT-PCR and Western blotting, and levels of related protein cyclin D1, Bc1-2,
      and SMRT by Western blotting. We also investigated the cell cycle and apoptosis
      via FCM, and cell proliferation by Cell Counting Kit-8 assay. We found that p65
      siRNA could effectively reduce the p65 mRNA and protein expression, arrest cells
      in G0/G1 phase, inhibit the proliferation and increase the apoptosis of THP-1
      cells, and intratumoral injection of p65 siRNA could suppress tumor growth in
      nude mice. We also found that when down regulation of p65, the expression of
      cyclin D1 and Bc1-2 decreased, and the expression of SMRT increased in vitro and
      vivo. All these findings suggest that NF-kappaB p65 maybe an attractive candidate
      for the therapeutic targeting of acute monocytic leukemia.

PMID- 21901539
TI  - [Acute ischemic stroke. New approaches to antithrombotic treatment].
AB  - The only recommended therapy in the acute phase of ischemic stroke is
      thrombolysis within 4.5-(6) h after symptom onset. For secondary stroke
      prevention platelet inhibitors or, in cases of cardiac embolism, anticoagulants
      are used. However, these substances bear significant limitations: either they
      show only moderate efficacy (platelet inhibitors), or they are associated with a
      considerable bleeding risk (rt-PA, anticoagulants). Although the majority of
      strokes are caused by embolic or thrombotic vessel occlusion, strikingly little
      is known about the pathophysiological role of platelets and their local function
      in the brain vasculature. The recent development of novel transgenic mouse lines
      paved the way for the in-depth analysis of the different molecular steps of
      thrombus formation involving platelets and the plasma coagulation cascade in
      models of acute ischemic stroke. It was demonstrated that prevention of early
      platelet adhesion to the damaged vessel wall by blocking the platelet surface
      receptors GPIbalpha or GPVI dramatically protects against experimental stroke
      without increasing the frequency of intracranial hemorrhage. Moreover, the
      critical involvement of the blood coagulation factor XII (FXII)-driven intrinsic
      coagulation cascade in thrombus formation during the course of ischemic brain
      damage could be unraveled thereby disproving established concepts of hemostasis.
      Based on these findings novel pharmacological blockers of GPIbalpha and FXIIa
      were designed that likewise proved to be safe and effective in animal stroke
      studies. Those compounds now lay the groundwork for a novel and intriguing
      concept in ischemic stroke and other thromboembolic diseases: antithrombosis
      devoid of any bleeding complications. Further preclinical testing is currently
      ongoing.

PMID- 21901540
TI  - Addressing the Impact of Atmospheric Nitrogen Deposition on Western European
      Grasslands.
AB  - There is a growing evidence base demonstrating that atmospheric nitrogen
      deposition presents a threat to biodiversity and ecosystem function in acid
      grasslands in Western Europe. Here, we report the findings of a workshop held for
      European policy makers to assess the perceived importance of reactive nitrogen
      deposition for grassland conservation, identify areas for policy development in
      Europe and assess the potential for managing and mitigating the impacts of
      nitrogen deposition. The importance of nitrogen as a pollutant is already
      recognized in European legislation, but there is little emphasis in policy on the
      evaluation of changes in biodiversity due to nitrogen. We assess the potential
      value of using typical species, as defined in the European Union Habitats
      Directive, for determining the impact of nitrogen deposition on acid grasslands.
      Although some species could potentially be used as indicators of nitrogen
      deposition, many of the typical species do not respond strongly to nitrogen
      deposition and are unlikely to be useful for identifying impact on an individual
      site. We also discuss potential mitigation measures and novel ways in which
      emissions from agriculture could be reduced.

PMID- 21901541
TI  - Examining the criterion validity of CBCL and TRF problem scales and items in a
      large Singapore sample.
AB  - This study examined the criterion validity of the Child Behavior Checklist (CBCL)
      and Teacher's Report Form (TRF) problem scales and items in demographically
      matched Singapore samples of referred and non-referred children (840 in each
      sample for the CBCL and 447 in each sample for the TRF). Internal consistency
      estimates for both the CBCL and TRF scales were good. Almost all CBCL and TRF
      problem scales and items significantly discriminated between referred and non
      referred children, with referred children scoring higher, as expected. The
      largest referral status effects were on attention problems scales and their
      associated items, with the TRF having larger effects than the CBCL. Effect sizes
      for demographic variables such as age, gender, ethnicity and SES were much
      smaller than effect sizes for referral status, across both the CBCL and TRF forms
      and at both the scale and item levels. These findings suggest that teachers can
      be effective partners in identifying children who need mental health services and
      those who do not.

PMID- 21901542
TI  - Emotion regulation and aggressive behavior in preschoolers: the mediating role of
      social information processing.
AB  - This study examined whether the relation between maladaptive emotion regulation
      and aggression was mediated by deviant social information processing (SIP).
      Participants were 193 preschool children. Emotion regulation and aggression were
      rated by teachers. Deviant SIP (i.e., attribution of hostile intent, aggressive
      response generation, aggressive response evaluation and decision) was measured
      from children's responses to hypothetical social conflicts. Findings revealed
      that the relation between maladaptive emotion regulation and aggression was
      direct and not mediated by SIP biases (i.e., aggressive response generation,
      aggressive response evaluation and decision). Results are discussed from a
      theoretical and methodological perspective.

PMID- 21901543
TI  - Longitudinal predictors of psychiatric disorders in very low birth weight adults.
AB  - The purpose of this study was to determine risk and protective factors for adult
      psychiatric disorders in very low birth weight (VLBW, birth weight <1,501 g)
      survivors. 79 of 154 (51%) VLBW subjects recruited at birth were assessed in
      early adulthood (24-27 years). Participants were screened for a psychiatric
      disorder; those elevated were invited to attend a structured clinical interview
      to determine a clinical diagnosis. Longitudinal variables measured from birth and
      at ages 2, 5, 14 and 18 years were included in analyses. Perinatal, developmental
      and social environmental risk factors failed to predict psychiatric disorder in
      adulthood in this cohort of VLBW survivors. Instead, low self-esteem at age 18
      (odds ratio [OR] = 1.05, 95% confidence interval [CI] = 1, 1.11, p = 0.05) and
      the adult social environment (high rates of negative life event stress at the
      time of assessment: OR = 1.39, CI = 1.10, 1.76, p = 0.02), contributed
      significantly to adult psychiatric outcomes.

PMID- 21901544
TI  - Proceedings of the diffuse intrinsic pontine glioma (DIPG) Toronto Think Tank:
      advancing basic and translational research and cooperation in DIPG.
AB  - Diffuse intrinsic pontine glioma (DIPG) nearly exclusively affects children. The
      prognosis of DIPGs has remained grim despite more than three decades of clinical
      research and numerous clinical trials. More than 90% of the children with DIPG
      will succumb within 2 years of diagnosis. The tumor's incidence is still
      undefined, but data suggest 100-150 affected children annually in the US. The
      single proven effective treatment modality in DIPG remains radiation therapy. For
      the majority of patients however this treatment is only of transient
      effectiveness. Recent breakthroughs in the understanding of the molecular biology
      of DIPG have raised new hope and opened new avenues for therapeutic options. The
      advancement of basic and translational research and cooperation was the objective
      of the Toronto Think Tank, as new approaches are urgently needed.

PMID- 21901545
TI  - 2,5-Hexanedione induces human ovarian granulosa cell apoptosis through BCL-2,
      BAX, and CASPASE-3 signaling pathways.
AB  - Studies have shown that 2,5-hexanedione (2,5-HD) is the main active metabolite of
      n-hexane in the human body. The toxicity of n-hexane and 2,5-hexanedione has been
      extensively researched, but toxicity to the reproductive system, especially the
      impact on female reproductive function, has been less frequently reported. In
      this study, we exposed human ovarian granulosa cells to 0, 16, 64, and 256 MUM
      2,5-HD in vitro for 24 h. Through hematoxylin-eosin (HE) staining, Hoechst 33342
      staining, transmission electron microscopy, and flow cytometry using FITC-Annexin
      V/PI double staining, 2,5-HD was demonstrated to cause significant apoptosis of
      human ovarian granulosa cells in a dose-dependent manner. As part of our
      continuing studies, we investigated the underlying apoptosis mechanism of human
      ovarian granulosa cells exposed to 0, 16, 64, and 256 MUM 2,5-HD in vitro for 24
      h. Real-time quantitative PCR and Western blot analysis were used to detect
      changes in the expression of the apoptosis-related BCL-2 family (BCL-2, BAX) and
      CASPASE family (CASPASE-3) with increasing 2,5-HD concentration. The results
      showed that with increasing 2,5-HD doses, the expression of BCL-2 decreased.
      However, a marked dose-dependent increase in the expression of BAX and active
      CASPASE-3 (p17) was observed in human ovarian granulosa cells. These results
      suggest that the mechanisms of 2,5-HD causing increased apoptosis in human
      ovarian granulosa cells might be through BCL-2, BAX, and CASPASE-3 signaling
      pathways.

PMID- 21901546
TI  - Estimation of aneurysm wall stresses created by treatment with a shape memory
      polymer foam device.
AB  - In this study, compliant latex thin-walled aneurysm models are fabricated to
      investigate the effects of expansion of shape memory polymer foam. A simplified
      cylindrical model is selected for the in-vitro aneurysm, which is a
      simplification of a real, saccular aneurysm. The studies are performed by
      crimping shape memory polymer foams, originally 6 and 8 mm in diameter, and
      monitoring the resulting deformation when deployed into 4-mm-diameter thin-walled
      latex tubes. The deformations of the latex tubes are used as inputs to physical,
      analytical, and computational models to estimate the circumferential stresses.
      Using the results of the stress analysis in the latex aneurysm model, a
      computational model of the human aneurysm is developed by changing the geometry
      and material properties. The model is then used to predict the stresses that
      would develop in a human aneurysm. The experimental, simulation, and analytical
      results suggest that shape memory polymer foams have potential of being a safe
      treatment for intracranial saccular aneurysms. In particular, this work suggests
      oversized shape memory foams may be used to better fill the entire aneurysm
      cavity while generating stresses below the aneurysm wall breaking stresses.

PMID- 21901547
TI  - Identification of candidate genes in rice for resistance to sheath blight disease
      by whole genome sequencing.
AB  - Recent advances in whole genome sequencing (WGS) have allowed identification of
      genes for disease susceptibility in humans. The objective of our research was to
      exploit whole genome sequences of 13 rice (Oryza sativa L.) inbred lines to
      identify non-synonymous SNPs (nsSNPs) and candidate genes for resistance to
      sheath blight, a disease of worldwide significance. WGS by the Illumina GA IIx
      platform produced an average 5* coverage with ~700 K variants detected per line
      when compared to the Nipponbare reference genome. Two filtering strategies were
      developed to identify nsSNPs between two groups of known resistant and
      susceptible lines. A total of 333 nsSNPs detected in the resistant lines were
      absent in the susceptible group. Selected variants associated with resistance
      were found in 11 of 12 chromosomes. More than 200 genes with selected nsSNPs were
      assigned to 42 categories based on gene family/gene ontology. Several candidate
      genes belonged to families reported in previous studies, and three new regions
      with novel candidates were also identified. A subset of 24 nsSNPs detected in 23
      genes was selected for further study. Individual alleles of the 24 nsSNPs were
      evaluated by PCR whose presence or absence corresponded to known resistant or
      susceptible phenotypes of nine additional lines. Sanger sequencing confirmed
      presence of 12 selected nsSNPs in two lines. "Resistant" nsSNP alleles were
      detected in two accessions of O. nivara that suggests sources for resistance
      occur in additional Oryza sp. Results from this study provide a foundation for
      future basic research and marker-assisted breeding of rice for sheath blight
      resistance.

PMID- 21901548
TI  - Fine mapping and comparative genomics integration of two quantitative trait loci
      controlling resistance to powdery mildew in a Spanish barley landrace.
AB  - The intervals containing two major quantitative trait loci (QTL) from a Spanish
      barley landrace conferring broad spectrum resistance to Blumeria graminis were
      subjected to marker saturation. First, all the available information on recently
      developed marker resources for barley was exploited. Then, a comparative genomic
      analysis of the QTL regions with other sequenced grass model species was
      performed. As a result of the first step, 32 new markers were added to the
      previous map and new flanking markers closer to both QTL were identified. Next,
      syntenic integration revealed that the barley target regions showed homology with
      regions on chromosome 6 of rice (Oryza sativa), chromosome 10 of Sorghum bicolor
      and chromosome 1 of Brachypodium distachyon. A nested insertion of ancestral
      syntenic blocks on Brachypodium chromosome 1 was confirmed. Based on sequence
      information of the most likely candidate orthologous genes, 23 new barley unigene
      derived markers were developed and mapped within the barley target regions. The
      assessment of colinearity revealed an inversion on chromosome 7HL of barley
      compared to the other three grass species, and nearly perfect colinearity on
      chromosome 7HS. This two-step marker enrichment allowed for the refinement of the
      two QTL into much smaller intervals. Inspection of all predicted proteins for the
      barley unigenes identified within the QTL intervals did not reveal the presence
      of resistance gene candidates. This study demonstrates the usefulness of
      sequenced genomes for fine mapping and paves the way for the use of these two
      loci in barley breeding programs.

PMID- 21901549
TI  - Neural stem cells over-expressing brain-derived neurotrophic factor (BDNF)
      stimulate synaptic protein expression and promote functional recovery following
      transplantation in rat model of traumatic brain injury.
AB  - Brain-derived neurotrophic factor (BDNF) plays an essential regulatory role in
      the survival and differentiation of various neural cell types during brain
      development and after injury. In this study, we used neural stem cells (NSCs)
      genetically modified to encode BDNF gene (BDNF/NSCs) and naive NSCs
      transplantation and found that BDNF/NSCs significantly improved neurological
      motor function following traumatic brain injury (TBI) on selected behavioral
      tests. Our data clearly demonstrate that the transplantation of BDNF/NSCs causes
      overexpression of BDNF in the brains of TBI rats. The number of surviving
      engrafted cells and the proportion of engrafted cells with a neuronal phenotype
      were significantly greater in BDNF/NSCs than in naive NSCs-transplanted rats. The
      expression of pre- and post-synaptic proteins and a regeneration-associated gene
      in the BDNF/NSCs-transplanted rats was significantly increased compared to that
      in NSCs-transplanted rats, especially at the early stage of post-transplantation.
      These data suggest that neurite growth and overexpression of synaptic proteins in
      BDNF/NSCs-transplanted rats are associated with the overexpression of BDNF, which
      is hypothesized to be one of the mechanisms underlying the improved functional
      recovery in motor behavior at the early stage of cell transplantation following
      TBI. Therefore, the protective effect of the BDNF-modified NSCs transplantation
      is greater than that of the naive NSCs transplantation.

PMID- 21901550
TI  - Suicidal ligature strangulation utilizing cable ties: a report of three cases.
AB  - In 2006 the US National Vital Statistics Report recorded 33,300 suicides in the
      United States, of which hanging, strangulation and suffocation combined to
      account for 7,491 (22.5%) of the cases. Self strangulation by ligature is
      uncommon and in the majority of cases, scarves, belts, neckties and rope are
      used. We report three instances where cable ties were secured around the neck in
      order to commit suicide. All had a history of depression. One was a 37-year-old
      man who used a belt to complete the act after an unsuccessful attempt to use
      cable ties. The second was a 63-year old woman who used multiple cable ties to
      accomplish her goal. In the third case a tensioning tool was used by a 54-year
      old man to tighten a cable tie around his neck during self strangulation.
      Utilization of a tool to tighten the cable ties has not previously been reported.

PMID- 21901551
TI  - Enhanced iron availability by protein glycation may explain higher infection
      rates in diabetics.
AB  - Serum proteins exist in a state of higher glycation among individuals with poor
      glycemic control, notably diabetics. These non-enzymatic modifications via the
      Maillard reaction have far reaching effects on metabolism and regulation, and may
      be responsible for increased infection rates within this population. Here we
      explore the effects of glycation on iron metabolism and innate immunity by
      investigating the interaction between siderophores and bovine serum albumin
      (BSA). Using a quartz crystal microbalance with dissipation monitoring to
      quantify association rates, glycated BSA exhibited a significantly reduced
      affinity for apo and holo enterobactin compared to a non-glycated BSA standard.
      Bacterial growth assays in the presence of BSA and under iron-limited conditions
      indicated the growth rate of enterobactin-producing E. coli increased
      significantly when the BSA was in a glycated form. The results, in addition to
      data in the literature, support the hypothesis that glycation of serum proteins
      may effectively increase the available free iron pool for bacteria in blood serum
      and weaken our innate immunity. This phenomenon may be partially responsible for
      higher infection rates in some diabetics, especially those with poor glycemic
      control.

PMID- 21901553
TI  - [Certification in the healthcare system. What happens when the certificate is not
      awarded?].
AB  - A quality certification is nowadays an important competitive factor for clinics
      and other institutions in Germany. The best known procedures are certification
      according to the norm DIN EN ISO, the German certification procedure in the
      healthcare system KTQ (Cooperation for Quality and Transparency in Healthcare)
      and the procedures of the German Cancer Society or medical professional
      societies. The majority of German clinics, centers, practices and nursing
      institutions are certified according to one of these procedures. In some areas
      certification is mandatory and a prerequisite for patient care, e.g. for
      rehabilitation institutions. But even in the field of acute medicine
      certification is an important proof that quality requirements have been fulfilled
      and has an effect on the economic situation. The aim of a visitation or audit is
      always to check whether the requirements of the appropriate certification
      procedure have been fulfilled. The actual procedure and the course can however,
      be organized differently. The failure to obtain certification is a very
      unpleasant situation for all concerned and can have negative effects on the image
      of the institution. Such a failure can most probably be avoided by good
      preparation and if necessary external consultation or internal qualification by
      colleagues. In most cases the certificate can be successfully obtained at least
      by the second attempt. Appropriate regulations are made by all procedures.
      Basically a thorough cost-benefit analysis should be carried out before deciding
      to apply for certification.

PMID- 21901552
TI  - Treatment of elderly acute myeloid leukemia patients.
AB  - OPINION STATEMENT: Older patients with acute myelogenous leukemia (AML) fare much
      less well than younger patients with the same disease due to a combination of
      comorbidities and intrinsic disease resistance. Likely due to aging of the US
      population, the median age of AML patients at diagnosis has increased from 68 to
      72 years. AML is a heterogeneous disease, particularly in older patients, making
      therapeutic decisions challenging. Older patients who are 'fit' for intensive
      chemotherapy and would have a reasonable chance to benefit based on host and
      disease characteristics should receive standard induction chemotherapy with 7
      days of continuous infusion of cytarabine and at least 60 mg/m(2) daunorubicin
      daily for 3 days. Therapeutic options for patients who are not candidates for or
      are not likely to respond to intensive therapy include clofarabine, low intensity
      chemotherapy such as low dose cytarabine, hypomethylating agents, or
      investigational agents. For older AML patients in complete remission, post
      remission or consolidation chemotherapy with repeat induction or modified high
      dose cytarabine may offer a small chance for long term disease-free survival.
      Selected older patients who achieve remission by any means should be considered
      for reduced-intensity stem cell transplantation which may offer improved chances
      of cure and survival compared with standard post-remission chemotherapy.

PMID- 21901554
TI  - [Quality management systems are compulsory: clinics have the choice. Comparison
      of the systems DIN EN ISO 9000 ff, KTQ and EFQM].
AB  - According to SS135-137 SGB V (German Civil Code), German hospitals are required
      to introduce and develop an institutional quality management (QM) system. They
      are, however, currently not obliged to undergo a certification. The prime
      responsibility to introduce a QM system lies with the top management. The aim is
      to continuously monitor and improve the quality of the processes and practices in
      the hospital. QM systems are one of the major constituents which influence the
      prosperity of an enterprise. Hospitals are able to improve the quality of their
      processes without significantly increasing the costs. The Excellence Barometer(r)
      Health Care (ExBa) of the Fraunhofer Institute has shown that deficits are
      usually not identified in the professional competence of the medical personnel
      but rather in respect to leadership abilities, communication and motivation. The
      introduction of QM in a hospital requires an in-depth familiarity with the
      various QM systems to select an appropriate model for the own institution. The
      systems most commonly in use in German hospitals are DIN EN ISO ff, EFQM and
      KTQ(r). The article illustrates and compares the layout, requirements and
      assessment criteria of the various systems.

PMID- 21901555
TI  - Insertional variability of four transposable elements and population structure of
      the midge Chironomus riparius (Diptera).
AB  - The dipteran Chironomus riparius is found across the entire Palearctic region;
      its larvae are among the most abundant macroinvertebrates inhabiting inland
      waterbodies. Chironomid larvae have been extensively used in ecotoxicological and
      cytogenetic research, but relatively little is known on the population structure
      of this species. Transposable elements (TEs) are DNA sequences that are capable
      of autonomous replication; the number and genomic location of TE insertions
      varies across individuals; this variability is increasingly being used in
      population studies. Several TEs had been characterized in Chironomids; this
      enabled the analysis of insertional variability of four different TEs in six
      natural populations of C. riparius from Italy, Bulgaria and Russia using a PCR
      based method, transposon insertion display (TID). The method allows to obtain
      dominant markers, similar to AFLP. In all populations, TE insertions showed high
      individual polymorphism, while median copy numbers of the same TEs did not vary
      between populations. Analysis of molecular variance (AMOVA) detected significant
      differentiation between populations for three of the TEs; although no correlation
      between genetic and geographic distances was found, the corresponding population
      structures were found to be significantly correlated and indicate a degree of
      isolation by distance. TEs belonging to different classes have different
      mechanisms of replication, resulting in different transposition rates of
      mobilization; the finding of mostly concordant population structuring for three
      of the TEs indicates that population dynamics contributed significantly in
      shaping the detected insertional polymorphism.

PMID- 21901557
TI  - Is shock wave lithotripsy efficient for the elderly stone formers? Results of a
      matched-pair analysis.
AB  - The aim of the study was to evaluate the impact of age on the efficacy of
      extracorporeal shock wave lithotripsy (SWL), in a comparative study based on the
      principles of matched-pair analysis. Over a period of 4 years, 2,311 patients
      were treated with SWL in a tertiary referral center. Patient and stone data were
      recorded in a prospective electronic database. Among these patients, 115 (4.97%)
      were older than 70 years of age and fulfilled the criteria for inclusion in the
      study (Group A). For the purposes of the comparative analysis, Group A patients
      were matched for gender and stone parameters (side, location of stone, and
      diameter +/-2 mm) with a control group of patients under the age of 70 (Group B).
      Following matching, the patients' electronic medical records were reviewed, to
      identify SWL success rates at 3 months and McNemar's test was used to compare the
      efficacy of SWL between the two groups. Matching was possible in all cases. The
      results indicate that there were no statistically significant differences in the
      mean number of SWL sessions or in the mean number of impulses per session between
      the two groups. The overall stone clearance rate achieved by SWL alone was 71.3%
      for Group A and 73.9% for group B. Discordant pairs were found in 37 cases (in 17
      pairs only patients in Group A became stone-free, while in 20 pairs only patients
      in Group B became stone-free). By using McNemar's test, the difference in stone
      clearance rates between the two groups was not found to be statistically
      significant (p = 0.742). A total of 22 patients (19.1%) in Group A and 17
      patients (14.7%) in Group B underwent an adjuvant procedure to achieve stone
      clearance. McNemar's test also revealed the absence of any statistically
      significant difference in SWL success rates between older and younger patients in
      the subgroups of patients presenting with either ureteric or renal stones (p =
      0.727 and p = 0.571, respectively). In conclusion, SWL is still considered one of
      the first-line tools for geriatric patients suffering from urolithiasis, as
      increased age alone does not seem to adversely affect the efficacy of SWL.

PMID- 21901556
TI  - Probiotic therapy: immunomodulating approach toward urinary tract infection.
AB  - Urinary tract infection (UTI) is an extremely common health problem, with an
      unpredictable history. Members of enterobacteriaceae family such as Escherichia
      coli, which are normal inhabitants of human intestines, account for the majority
      of these uncomplicated infections. Rarely, UTI can result from virus or fungus.
      There is a close correlation between loss of the normal genital microbiota,
      particularly Lactobacillus species, and an increased incidence of genital and
      bladder infections. Although antimicrobial agents are generally effective in
      eradicating these infections, there is a high incidence of recurrence. Use of
      Lactobacillus species to combat UTI is now giving modern concept of modern
      genitourinary vaccine with the facts that it not only maintains low pH of the
      genital area, produces hydrogen peroxide and hinders the growth of E. coli but
      also activates Toll-like receptor-2 (TLR2), which produces interleukin-10 (IL-10)
      and myeloid differentiation factor 88 (MyD88). E. coli activates TLR4, which is
      responsible for the activation of IL-12, extracellular signal-regulated kinase
      (ERK) and c-Jun N-terminal kinase (JNK). This process downregulates inflammatory
      reactions caused due to pathogens. Current review covers the probiotics-based TLR
      therapy and shed some knowledge for the use of Lactobacillus species as
      probiotics.

PMID- 21901558
TI  - How to document and report orthopedic complications in clinical studies? A
      proposal for standardization.
AB  - INTRODUCTION: The documentation of complications is critical for the evaluation
      of therapeutic interventions in orthopedics. However, there is a lack of accepted
      methodological standardization and definitions. We propose a concept to support
      the consensus development of a standardized management and classification of
      complications in clinical research. METHODS: Complication events are examined
      regarding their clinical presentation, their timing of occurrence as well as
      their potential causal interrelationship for any given patient. Their clinical
      presentation is distinguished by their likely triggers, their therapeutic
      management, and their outcome. Complications are events (including relevant
      deviations from their expected healing process) that are harmful to patients and
      can be described as local to the treated injury/disease or systemic (when they
      affect the rest of the body). The treatment of a complication, e.g. by way of an
      unplanned surgical intervention, and its outcome should be carefully documented.
      Complication review boards with independent clinicians should be established to
      validate complication records. APPLICATION AND RELEVANCE: In this proposal, a
      number of complication examples are presented to illustrate the concept and
      demonstrate its practical use. This management and classification system has
      already proven valuable in the documentation and analysis of complication data
      from a number of published clinical studies. Because of this new standardized
      assessment process, it facilitates the communication of complications between
      clinicians and researchers, and helps to develop clear definitions for specific
      orthopedic complications.

PMID- 21901559
TI  - Peripheral blood guanylyl cyclase c (GCC) expressions are associated with
      prognostic parameters and response to therapy in colorectal cancer patients.
AB  - Guanylyl cyclase C (GCC) is expressed exclusively in normal intestinal mucosal
      cells, primary and metastatic colorectal cancers (CRC). The aim of this study was
      to determine the possible association between the GCC expressions in peripheral
      blood, prognostic parameters and response to chemotherapy in CRC patients. Fourty
      nine metastatic CRC patients and 41 healthy controls with similar age and sex
      were included to this study. Peripheral blood GCC expressions are measured by the
      reverse transcriptase-polymerase chain reaction (RT-PCR) method. Interstingly, no
      GCC expression was measured in healthy controls but GCC expressions of the
      patients were detectable. Although there was a significant reduction in GCC
      expressions in 30 patients with regression (from 5.46 +/- 4.12 to 0.06 +/- 0.03,
      p < 0.0001), marked increase in GCC expressions was observed in 19 patients with
      progression following chemotherapy (from 0.43 +/- 0.19 to 1.38 +/- 0.52, p =
      0.0174). Significant correlation was found between the GCC expressions and
      carbohydrate antigen 19-9 (CA19-9) levels (p = 0.0041) in 30 patients with
      regression before chemotherapy. Marked correlation was also detected between the
      GCC expressions and carcinoembryonic antigen (CEA) levels (p = 0.0072) in 19
      patients with progression before chemotherapy. The results of the present study
      suggest that peripheral blood GCC expressions along with CEA and CA19-9 can be
      used to determine the early respose to chemotherapy in patients with metastatic
      CRC. These findings imply that higher expression of GCC in peripheral blood seems
      to be an indicator of good therapeutic response to chemotherapy and remission.
      Monitoring the peripheral blood GCC expressions may allow employing different
      treatment options to metastatic CRC patients.

PMID- 21901560
TI  - Intraocular pressure reduction in normal-tension glaucoma patients in South
      Korea.
AB  - To evaluate the potential benefit of intraocular pressure (IOP) reduction in
      normal-tension glaucoma (NTG) patients in South Korea. A retrospective, multi
      center analysis of Korean NTG patients with 5-years follow-up, typical
      glaucomatous optic disc and/or visual field changes and no recorded IOP >21 mmHg.
      Progression was identified by Advanced Glaucoma Intervention Study visual field
      scoring. There were 90 (42%) progressed patients and 127 (58%) stable patients
      included in the study. Mean IOP measured higher in the progressed (14.3 +/- 2.2
      mmHg) than stable patients (14.0 +/- 1.9 mmHg), but was not statistically
      different between the groups (P = 0.29). The mean IOP that best discriminated
      stable patients was <=15 mmHg, but no statistical difference existed in the
      numbers of progressed versus stable patients at <=15 mmHg compared to >15 mmHg (P
      = 0.07). Multivariate regression analysis showed that the baseline number of
      glaucoma medicines and visual field as well as mean, peak and fluctuation of IOP
      were significant risk factors for glaucomatous progression (P < 0.01). This study
      suggests that in Korean NTG patients, despite relatively similar IOPs between
      progressed and stable patients, and based on multivariate regression analysis,
      IOP may be a risk factor for glaucomatous progression.

PMID- 21901562
TI  - [Endemic air-borne contact dermatitis? Frequent occurrence of a rare contact
      allergy in a waste collection facility].
AB  - Numerous cases of work-related air-borne contact dermatitis of the face were
      encountered in a waste collection facility. Potential allergens contained in the
      dust at the facility could be identified. In 5 of 7 symptomatic workers a type-IV
      sensitization to p-aminodiphenylamine could be documented. Since there is no
      commercial patch test preparation for p-aminodiphenylamine available, it had to
      be prepared for each patient individually. After identifying the allergen, a
      change in the work routine led to a reduction of dust emissions and afterwards no
      cases of air-borne contact dermatitis of the face recurred.

PMID- 21901561
TI  - [Cutaneous malignancies in occupationally-induced scars].
AB  - BACKGROUND: The occurrence of neoplasms in injury scars--as consequence of
      occupational accidents--may lead to compensation according to the statutory
      accident insurance regulations. According to newer regulatory attempts in
      occupational dermatology, certain criteria have to be met before the diagnosis of
      a neoplasm induced by a scar is accepted and compensation is due. MATERIAL AND
      METHODS: Based on a retrospective analysis of 217 dermatological claim files
      between 2007 and 2009 of the IPA (including 22 follow-ups), medical opinions on
      neoplasms developing in possible occupational scars were re-evaluated using
      criteria of the German social accident insurance and the Bamberg medical
      bulletin, part II (Bamberger Merkblatt, BM II) to see how well they qualified for
      recognition as an occupational or accident-related disorder. RESULTS: Three cases
      were identified where a neoplasm was suspected of having developed in an
      occupationally-related scar. One of the insured events entitled for compensation.
      Following the guidelines of the BM II, this case was approved as an occupational
      disease secondary to injuries with resultant reduction in earning capacity,
      whereas the others did not meet the requirements. CONCLUSIONS: Two problems in
      evaluating malignant tumors in occupational scars are the long latency period and
      the documentation of a scar. The tumor excision specimen should be histologically
      re-examined to document the presence of an associated scar.

PMID- 21901563
TI  - [Current contact allergens].
AB  - Ever-changing exposure to contact allergens, partly due to statutory directives
      (e.g. nickel, chromate, methyldibromo glutaronitrile) or recommendations from
      industrial associations (e.g. hydroxyisohexyl 3-cyclohexene carboxaldehyde),
      requires on-going epidemiologic surveillance of contact allergy. In this paper,
      the current state with special focus in fragrances and preservatives is described
      on the basis of data of the Information Network of Departments of Dermatology
      (IVDK) of the year 2010. In 2010, 12,574 patients were patch tested in the
      dermatology departments belonging to the IVDK. Nickel is still the most frequent
      contact allergen. However the continuously improved EU nickel directive already
      has some beneficial effect; sensitization frequency in young women is dropping.
      In Germany, chromate-reduced cement has been in use now for several years,
      leading to a decline in chromate sensitization in brick-layers. Two fragrance
      mixes are part of the German baseline series; they are still relevant. The most
      important fragrances in these mixes still are oak moss absolute and
      hydroxyisohexyl 3-cyclohexene carboxaldehyde. However, in relation to these
      leading allergens, sensitization frequency to other fragrances contained in the
      mixes seems to be increasing. Among the preservatives, MCI/MI has not lost its
      importance as contact allergen, in contrast to MDBGN. Sources of MCI/MI
      sensitization obviously are increasingly found in occupational context.
      Methylisothiazolinone is a significant allergen in occupational settings, and
      less frequently in body care products.

PMID- 21901564
TI  - Impact of intermediate mammography assessment on the likelihood of false-positive
      results in breast cancer screening programmes.
AB  - OBJECTIVES: Breast cancer screening is offered to 100% of the target population
      in Spain and intermediate mammograms (IMs) are sometimes indicated. This study
      was aimed at analysing the frequency of IMs, the factors determining their
      recommendation, and their impact on the risk of false-positive results and the
      detection rate. METHODS: Data from 3,471,307 mammograms from Spanish breast
      cancer screening programmes were included. RESULTS: 3.36% of the mammograms were
      IMs. The factors associated with the use of IMs were age, initial screening,
      previous invasive tests, a familial history of breast cancer and use of hormone
      replacement therapy. In screening episodes with an IM, the probability of a false
      positive result was 13.74% (95% CI: 13.43-14.05), almost double that in episodes
      without IMs (6.02%, 95% CI 5.99-6.05). In young women with previous invasive
      procedures, a familial history of breast cancer or hormone replacement therapy
      use who were undergoing their initial screen, this probability was lower when IMs
      were performed. IMs always increased the detection rate. CONCLUSIONS: The factors
      prompting IMs should be characterised so that radiologists can systematise their
      recommendations according to the presence of the factors maximising the benefits
      and minimising the adverse effects of this procedure. KEY POINTS: Intermediate
      mammograms in breast screening offer potential benefits but also disadvantages.
      Intermediate mammograms increase the false-positive rate except in specific
      groups. Intermediate mammograms reduce the false-positive rate in younger women
      and initial screens. Intermediate mammograms also reduce false-positive results
      in women with personal risk factors. Intermediate mammograms increase cancer
      detection mainly in women without risk factors.

PMID- 21901565
TI  - Volumetric feedback ablation of uterine fibroids using magnetic resonance-guided
      high intensity focused ultrasound therapy.
AB  - OBJECTIVE: The purpose of this prospective multicenter study was to assess the
      safety and technical feasibility of volumetric Magnetic Resonance-guided High
      Intensity Focused Ultrasound (MR-HIFU) ablation for treatment of patients with
      symptomatic uterine fibroids. METHODS: Thirty-three patients with 36 fibroids
      were treated with volumetric MR-HIFU ablation. Treatment capability and technical
      feasibility were assessed by comparison of the Non-Perfused Volumes (NPVs) with
      MR thermal dose predicted treatment volumes. Safety was determined by evaluation
      of complications or adverse events and unintended lesions. Secondary endpoints
      were pain and discomfort scores, recovery time and length of hospital stay.
      RESULTS: The mean NPV calculated as a percentage of the total fibroid volume was
      21.7%. Correlation between the predicted treatment volumes and NPVs was found to
      be very strong, with a correlation coefficient r of 0.87. All patients tolerated
      the treatment well and were treated on an outpatient basis. No serious adverse
      events were reported and recovery time to normal activities was 2.3 +/- 1.8 days.
      CONCLUSION: This prospective multicenter study proved that volumetric MR-HIFU is
      safe and technically feasible for the treatment of symptomatic uterine fibroids.
      KEY POINTS: * Magnetic-resonance-guided high intensity focused ultrasound allows
      non-invasive treatment of uterine fibroids. * Volumetric feedback ablation is a
      novel technology that allows larger treatment volumes * MR-guided ultrasound
      ablation of uterine fibroids appears safe using volumetric feedback.

PMID- 21901567
TI  - [Anesthesiology and palliative medicine. Structured results of a prospective
      questionnaire-based survey in German hospitals].
AB  - BACKGROUND: Anesthesiology departments were often integrated into the primary
      formation of palliative activities in Germany. The aim of this study was to
      present the current integration of anesthesiology departments into palliative
      care activities in Germany. METHODS: The objective was to determine current
      activities of anesthesiology departments in in-hospital palliative care. A
      quantitative study was carried out based on a self-administered structured
      questionnaire used during telephone interviews. RESULTS: A total of 168 out of
      244 hospitals consented to participate in the study and the response rate was
      69%. In-hospital palliative care activities were reported for most of the
      surveyed hospitals. Only two hospitals in the maximum level of care reported no
      activities. Participation in these activities by anesthesiology departments was
      described in up to 92%. Historically, most activities are due to the commitment
      of individuals, whereas the development of palliative care of cancer pain
      services and hospital support teams took place in the university hospitals by
      2005. CONCLUSIONS: Until 2005 many university palliative care activities had
      their origins in cancer pain services. These were often integrated into
      anesthesiology departments. Currently, anesthesiology departments work as an
      integrative part of palliative medicine. However, it appears from the present
      results that there is a domination of internal medicine (especially hematology
      and oncology) in palliative activities in German hospitals. This allows the focus
      of palliative activities to be formed by subjective specialist interests. Such a
      state seems to be reduced by the integration of anesthesiology departments
      because of their neutrality with respect to faculty-specific medical interests.
      Advantages or disadvantages of these circumstances are not considered by the
      present investigation.

PMID- 21901566
TI  - [Intrinsic brain activity with pain].
AB  - Besides the responses to nociceptive stimuli other neural function modes of the
      brain are necessary to obtain a comprehensive understanding of pain processing in
      humans. During a resting state without extrinsic stimulation the human brain
      generates spontaneous low frequency fluctuations of neural activity. This
      intrinsic activity does not reflect random background noise but is highly
      organized in several networks. Based on the findings of recent functional imaging
      studies, the role of these resting state networks in acute and chronic pain is
      discussed.

PMID- 21901568
TI  - Abstracts of the Neurocritical Care Society 9th Annual Meeting. September 21-24,
      2011. Montreal, Canada.

PMID- 21901569
TI  - The measurement of the beta/alpha anomer composition within amorphous lactose
      prepared by spray and freeze drying using a simple (1)H-NMR method.
AB  - PURPOSE: Reports of the anomeric composition of amorphous lactose are rare and
      state a highly variable range of composition (between 0% and 60% w/w beta
      content). We aimed to develop a quantitative measurement by (1)H-NMR of alpha and
      beta anomer content in amorphous lactose produced by different production
      methods. METHODS: Amorphous lactose was prepared by spray and freeze drying 10%
      w/v aqueous solutions of lactose. NMR analysis was performed in DMSO; peak areas
      of partially resolved doublets at 6.3 and 6.6 ppm were used to calculate % of
      alpha and beta lactose present. Polarimetery was used to determine optical
      rotation of lactose solutions. RESULTS: Observed specific rotation for supplied
      crystalline alpha lactose monohydrate of 88 degrees  recorded in DMSO was
      constant for the length of a typical NMR experiment (max. 10 min). beta/alpha
      anomer contents of amorphous lactose measured by (1)H-NMR had standard deviations
      as low as 0.1% w/w (n = 6). Drying a lactose solution 4 h after its preparation
      led to almost 35% w/w difference in anomer composition within solid amorphous
      material compared to samples dried after only 30 min, e.g. for freeze dried
      samples, beta content was 60 +/- 0.1% w/w (4 h) and 25 +/- 1.0% w/w (30 min).
      Mutarotation leads to this increase in beta anomer concentration in aqueous
      solution and within the solid amorphous lactose stored at 25 degrees C. e.g.
      after 56 d storage the beta content of freeze dried lactose (30 min solution)
      increased from 25+/-1.0% to 50+/-0.5% w/w. CONCLUSION: A simple solution-based
      (1)H-NMR method for measurement of anomeric composition of lactose has been
      established. The solution beta/alpha ratio at the time of drying is mirrored in
      the composition of the resulting solid amorphous material. In order to produce a
      consistent anomer composition within spray and freeze dried amorphous lactose,
      the standing time for the feed solution should be greater than 4 h, such that the
      most dynamic region of the mutarotation profile has been exceeded. If the
      amorphous material has been formed from a solution that has not been allowed to
      equilibrate for 4 h, the resulting solid will continue to undergo mutarotation if
      trace amounts of moisture are present, until the anomeric beta/alpha ratio slowly
      approaches 1.7.

PMID- 21901571
TI  - Negative attentional set in the attentional blink: control is not lost.
AB  - The attentional blink (AB) refers to the finding that performance on the second
      of two targets (T1 and T2) in a rapidly presented stimulus stream is impaired
      when the targets are presented within 200-500 ms. This study investigates whether
      a negative attentional set, a form of top-down control, has an additional
      detrimental effect, and whether its influence is modulated by task demands. A
      negative attentional set was elicited through presentation of a pre-T1 distractor
      (D1), which belonged to the same category as T2. The presence of D1 impaired T2
      performance, and this negative effect was generally larger inside than outside
      the AB. Moreover, this D1 effect remained constant or was augmented when the
      demand on T1 processing was enhanced. These findings demonstrate that a negative
      attentional set is maintained even though the central system is engaged in the in
      depth processing of T1 during the AB.

PMID- 21901570
TI  - [Primary and secondary prevention of benign prostatic hyperplasia: current
      knowledge and implications for clinical management].
AB  - Histological benign prostatic hyperplasia (BPH) and the BPH disease are frequent,
      lead to a reduction of quality of life, are both progressive and potentially
      associated with complications in the lower and upper urinary tract. A
      PubMed/MEDLINE search was conducted for the years 1990 to 2011. This article
      summarizes known selective measures of primary and secondary disease
      prevention.Measures of primary disease prevention aim to inhibit histological BPH
      and the development of clinically relevant BPH. Weight loss, regular physical
      activity, vegetable consumption, alcohol intake, 5alpha-reductase inhibitors,
      avoidance of overweight and reduction of fatty food can reduce the probability of
      histological and clinical BPH. Selective measures of secondary prevention aim to
      inhibit disease progression and BPH-associated complications. The regular and
      long-term use of alpha1-blockers reduces lower urinary tract symptoms (LUTS) and
      inhibits symptomatic disease progression but cannot prevent BPH-associated
      complications (e.g. urinary retention or need for prostate surgery). 5alpha
      Reductase inhibitors can reduce the probability of symptomatic disease
      progression, urinary retention or need for surgery but the combination of alpha1
      blocker and 5alpha-reductase inhibitor is more efficacious than either
      monotherapy. Especially older men with enlarged prostates (>40 cm(3)) and
      elevated serum PSA concentration (>1.6 ug/l) profit from measures of secondary
      disease prevention.For primary disease prevention, data quality is low and early
      treatment with 5alpha-reductase inhibitors is not been approved. For secondary
      disease prevention, men with risk factors of disease progression should use a
      treatment containing 5alpha-reductase inhibitors. Despite several epidemiological
      and clinical investigations on BPH disease progression no official programme
      exists in Germany for disease prevention.

PMID- 21901572
TI  - Masked transposition effects for simple versus complex nonalphanumeric objects.
AB  - When two letters/digits/symbols are switched in a string (e.g., jugde-judge; 1492
      1942; *?$&-*$?&), the resulting strings are perceptually similar to each other
      and produce a sizable masked transposition priming effect with the masked priming
      same-different matching task. However, a parallel effect does not occur for
      strings of pseudoletters (e.g., [letters in the text]); Garcia-Orza, Perea, &
      Munoz, Quarterly Journal of Experimental Psychology, 63, 1603-1618, 2010). In the
      present study, we examined whether masked transposition priming is specific to
      alphanumeric stimuli or whether it also occurs with strings composed of other
      "objects"-namely, line drawings of common objects (Experiment 1) and geometrical
      shapes (Experiment 2). Results showed a significant masked transposition priming
      effect for geometrical shapes (e.g., [geometrical shapes in the text]), but not
      for line drawings of common objects (e.g., [symbols in the text]). These findings
      suggest that the mechanism involved in the coding of position in masked priming
      works only with perceptually simple, familiar "objects" (i.e., letters, numbers,
      symbols, or geometrical shapes), once their identities have been well
      ascertained.

PMID- 21901575
TI  - Changes in search rate but not in the dynamics of exogenous attention in action
      videogame players.
AB  - Many previous studies have shown that the speed of processing in attentionally
      demanding tasks seems enhanced following habitual action videogame play. However,
      using one of the diagnostic tasks for efficiency of attentional processing, a
      visual search task, Castel and collaborators (Castel, Pratt, & Drummond, Acta
      Psychologica 119:217-230, 2005) reported no difference in visual search rates,
      instead proposing that action gaming may change response execution time rather
      than the efficiency of visual selective attention per se. Here we used two hard
      visual search tasks, one measuring reaction time and the other accuracy, to test
      whether visual search rate may be changed by action videogame play. We found
      greater search rates in the gamer group than in the nongamer controls, consistent
      with increased efficiency in visual selective attention. We then asked how
      general the change in attentional throughput noted so far in gamers might be by
      testing whether exogenous attentional cues would lead to a disproportional
      enhancement in throughput in gamers as compared to nongamers. Interestingly,
      exogenous cues were found to enhance throughput equivalently between gamers and
      nongamers, suggesting that not all mechanisms known to enhance throughput are
      similarly enhanced in action videogamers.

PMID- 21901574
TI  - Signal detection evidence for limited capacity in visual search.
AB  - The nature of capacity limits (if any) in visual search has been a topic of
      controversy for decades. In 30 years of work, researchers have attempted to
      distinguish between two broad classes of visual search models. Attention-limited
      models have proposed two stages of perceptual processing: an unlimited-capacity
      preattentive stage, and a limited-capacity selective attention stage. Conversely,
      noise-limited models have proposed a single, unlimited-capacity perceptual
      processing stage, with decision processes influenced only by stochastic noise.
      Here, we use signal detection methods to test a strong prediction of attention
      limited models. In standard attention-limited models, performance of some
      searches (feature searches) should only be limited by a preattentive stage. Other
      search tasks (e.g., spatial configuration search for a "2" among "5"s) should be
      additionally limited by an attentional bottleneck. We equated average accuracies
      for a feature and a spatial configuration search over set sizes of 1-8 for
      briefly presented stimuli. The strong prediction of attention-limited models is
      that, given overall equivalence in performance, accuracy should be better on the
      spatial configuration search than on the feature search for set size 1, and worse
      for set size 8. We confirm this crossover interaction and show that it is
      problematic for at least one class of one-stage decision models.

PMID- 21901573
TI  - Incremental grouping of image elements in vision.
AB  - One important task for the visual system is to group image elements that belong
      to an object and to segregate them from other objects and the background. We here
      present an incremental grouping theory (IGT) that addresses the role of object
      based attention in perceptual grouping at a psychological level and, at the same
      time, outlines the mechanisms for grouping at the neurophysiological level. The
      IGT proposes that there are two processes for perceptual grouping. The first
      process is base grouping and relies on neurons that are tuned to feature
      conjunctions. Base grouping is fast and occurs in parallel across the visual
      scene, but not all possible feature conjunctions can be coded as base groupings.
      If there are no neurons tuned to the relevant feature conjunctions, a second
      process called incremental grouping comes into play. Incremental grouping is a
      time-consuming and capacity-limited process that requires the gradual spread of
      enhanced neuronal activity across the representation of an object in the visual
      cortex. The spread of enhanced neuronal activity corresponds to the labeling of
      image elements with object-based attention.

PMID- 21901576
TI  - Zero coronary calcium in the presence of severe isolated left main stenosis
      detected by CT coronary angiography in a patient with typical angina and
      equivocal myocardial perfusion SPECT.

PMID- 21901577
TI  - A modulatory effect of male voice pitch on long-term memory in women: evidence of
      adaptation for mate choice?
AB  - From a functionalist perspective, human memory should be attuned to information
      of adaptive value for one's survival and reproductive fitness. While evidence of
      sensitivity to survival-related information is growing, specific links between
      memory and information that could impact upon reproductive fitness have remained
      elusive. Here, in two experiments, we showed that memory in women is sensitive to
      male voice pitch, a sexually dimorphic cue important for mate choice because it
      not only serves as an indicator of genetic quality, but may also signal
      behavioural traits undesirable in a long-term partner. In Experiment 1, we report
      that women's visual object memory is significantly enhanced when an object's name
      is spoken during encoding in a masculinised (i.e., lower-pitch) versus feminised
      (i.e., higher-pitch) male voice, but that no analogous effect occurs when women
      listen to other women's voices. Experiment 2 replicated this pattern of results,
      additionally showing that lowering and raising male voice pitch enhanced and
      impaired women's memory, respectively, relative to a baseline (i.e.,
      unmanipulated) voice condition. The modulatory effect of sexual dimorphism cues
      in the male voice may reveal a mate-choice adaptation within women's memory,
      sculpted by evolution in response to the dilemma posed by the double-edged
      qualities of male masculinity.

PMID- 21901578
TI  - Expression of periostin during Xenopus laevis embryogenesis.
AB  - Periostin (postn) is a secreted, extracellular matrix protein containing an EMI
      domain as well as four fasciclin I-like (Fas1) domains. Postn protein functions
      in cell adhesion, cell mobility, cell proliferation and gene regulation. Earlier
      studies have shown that postn is involved in different developmental processes
      such as somitogenesis, cardiogenesis and bone formation. Intriguingly, postn
      seems to be a very good candidate to establish novel therapies against cancer and
      chronic heart defects. Here we describe for the first time the spatio-temporal
      expression profile of postn during early development of Xenopus laevis. By semi
      quantitative RT-PCR approaches, we demonstrate that postn is maternally
      expressed. Zygotic expression starts during early gastrulation and increases
      until stage 40. Whole mount in situ hybridization experiments revealed that postn
      is detectable in somites, the sensory layer of the epidermis, the roof plate, the
      notochord, the heart, migrating neural crest cells, cranial ganglia and forming
      cranial cartilage structures. Our results implicate a role of postn during
      Xenopus embryogenesis and represent a good starting point for future functional
      analyses.

PMID- 21901579
TI  - Transarterial ethylene vinyl alcohol copolymer visualization and penetration
      after embolization of life-threatening hemoptysis: technical and clinical
      outcomes.
AB  - OBJECTIVES: This study was designed to evaluate the feasibility of using ethylene
      vinyl alcohol copolymer (EVAC) for bronchial artery embolization (BAE) in
      patients with life-threatening hemoptysis and to compare the visualization and
      transarterial penetration of EVAC under fluoroscopy and computed tomography (CT).
      METHODS: Fifteen patients (mean age, 62.9 (range, 24-82) years) who were referred
      for life-threatening hemoptysis (27 month period) underwent BAE using EVAC. All
      patients had thoracic CT examination before and after BAE. Technical and clinical
      results were evaluated. Visibility and extent of cast penetration (graded 1-4) on
      fluoroscopy and postprocedure CT were assessed and compared. RESULTS: BAE was
      feasible in all but one artery (due to spasm; n=27; 96.4%). No procedure-related
      complications or deaths were detected. Two patients had recurrent bleeding in the
      following day (13.3%). Immediate clinical success was achieved in 14 cases
      (93.3%) after reembolization of pulmonary artery pseudoaneurysm in one patient
      (mean follow-up, 43.5 (range, 14-148) days). Visibility of the cast was possible
      in 73.3% of patients (n=11) under fluoroscopy (mean cast penetration 1.66) and in
      all patients under CT (mean cast penetration 2.06). The postinjection
      fluoroscopic visibility in 6 of 15 (40%) patients was inferior to CT (P<0.02).
      CONCLUSIONS: BAE with EVAC seems to be feasible and safe with immediate control
      of hemoptysis in most patients. The postinjection fluoroscopic visibility of EVAC
      under fluoroscopy was inferior to CT.

PMID- 21901580
TI  - JAG tearing technique with radiofrequency guide wire for aortic fenestration in
      thoracic endovascular aneurysm repair.
AB  - An innovative approach, the JAG tearing technique, was performed during thoracic
      endovascular aneurysm repair in a patient with previous surgical replacement of
      the ascending aorta with a residual uncomplicated type B aortic dissection who
      developed an aneurysm of the descending thoracic aorta with its lumen divided in
      two parts by an intimal flap. The proximal landing zone was suitable to place a
      thoracic stent graft. The distal landing zone was created by cutting the intimal
      flap in the distal third of the descending thoracic aorta with a radiofrequency
      guide wire and intravascular ultrasound catheter.

PMID- 21901581
TI  - Retrograde transvenous ethanol embolization of high-flow peripheral arteriovenous
      malformations.
AB  - PURPOSE: To report the clinical efficiency and complications in patients treated
      with retrograde transvenous ethanol embolization of high-flow peripheral
      arteriovenous malformations (AVMs). Retrograde transvenous ethanol embolization
      of high-flow AVMs is a technique that can be used to treat AVMs with a dominant
      outflow vein whenever conventional interventional procedures have proved
      insufficient. METHODS: This is a retrospective study of the clinical
      effectiveness and complications of retrograde embolization in five patients who
      had previously undergone multiple arterial embolization procedures without
      clinical success. RESULTS: Clinical outcomes were good in all patients but were
      achieved at the cost of serious, although transient, complications in three
      patients. CONCLUSION: Retrograde transvenous ethanol embolization is a highly
      effective therapy for high-flow AVMs. However, because of the high complication
      rate, it should be reserved as a last resort, to be used after conventional
      treatment options have failed.

PMID- 21901582
TI  - Patient experience, pain, and quality of life after lower limb angioplasty: a
      multisite prospective cohort study.
AB  - PURPOSE: To explore the experience of patients undergoing endovascular lower limb
      angioplasty and evaluate the improvements in quality of life and disease-related
      symptoms after the procedure. METHODS: Patients completed a questionnaire before
      treatment and three questionnaires after the procedure (immediately after the
      procedure, and again 4 weeks and 3 months later). Anxiety, patient understanding,
      procedure-related pain, and disease-related pain were assessed by a visual analog
      score (VAS). Complications, analgesic requirements, and satisfaction were
      recorded. Changes to quality of life were assessed by the validated SF36
      questionnaire. RESULTS: A total of 88 patients (41%) responded. Overall, disease
      related pain decreased over 3 months after the procedure. Smokers had more pain
      both before and after the procedure (P < 0.05). Explanation was considered better
      if provided by radiologist (P < 0.05). Sixty-nine percent of patients found the
      procedures less painful (mean VAS 2.5) than they had anticipated (VAS 5.5). Fifty
      percent of patients experienced adverse effects related to their puncture site,
      but this was highest among patients who had undergone the procedure before and
      smokers. The greatest quality-of-life improvements were in emotional and general
      health. Higher levels of disease-related pain were associated with worse general,
      emotional, and physical health (P < 0.05). CONCLUSION: Lower limb angioplasty
      provides symptomatic and quality-of-life improvements. Implementation of simple
      measures could improve patient satisfaction-for example, treatment should be
      explained by the radiologist in advance. Routine prescription of analgesics with
      particular attention to smokers and those undergoing repeat interventions is
      suggested.

PMID- 21901583
TI  - Biographical sketch: Georg Hermann von Meyer (1815-1892).
AB  - This biographical sketch on Georg Hermann von Meyer highlights the interactions
      in the 1860s that von Meyer, a famous anatomist, had with Karl Culmann, a famous
      structural engineer and mathematician. The published papers from this interaction
      caught the attention of Julius Wolff and stimulated his development of the
      trajectorial hypothesis of bone adaptation--now called "Wolff's Law." The
      corresponding translations are provided: (1) von Meyer's 1867 paper that
      highlights the regularity of arched trabecular patterns in various human bones,
      and his discussions with Culmann about their possible mechanical relevance; and
      (2) Wolff's 1869 paper that first mentions the correspondence of stress
      trajectories in a solid, crane-like structure to the arched trabecular patterns
      in the proximal human femur. This biographical sketch on Georg Hermann von Meyer
      corresponds to the historic texts, The Classic: The Architecture of the
      Trabecular bone (by von Meyer), and The Classic: On the Significance of the
      Architecture of the Spongy Substance for the Question of Bone Growth. A
      preliminary publication (by Wolff) available at DOIs 10.1007/s11999-011-2041-5 ,
      10.1007/s11999-011-2042-4 .

PMID- 21901584
TI  - Cell therapeutics in Parkinson's disease.
AB  - The main pathology underlying motor symptoms in Parkinson's disease (PD) is a
      rather selective degeneration of nigrostriatal dopamine (DA) neurons.
      Intrastriatal transplantation of immature DA neurons, which replace those neurons
      that have died, leads to functional restoration in animal models of PD. Here we
      describe how far the clinical translation of the DA neuron replacement strategy
      has advanced. We briefly summarize the lessons learned from the early clinical
      trials with grafts of human fetal mesencephalic tissue, and discuss recent
      findings suggesting susceptibility of these grafts to the disease process long
      term after implantation. Mechanisms underlying graft-induced dyskinesias, which
      constitute the only significant adverse event observed after neural
      transplantation, and how they should be prevented and treated are described. We
      summarize the attempts to generate DA neurons from stem cells of various sources
      and patient-specific DA neurons from fully differentiated somatic cells, with
      particular emphasis on the requirements of these cells to be useful in the
      clinical setting. The rationale for the new clinical trial with transplantation
      of fetal mesencephalic tissue is described. Finally, we discuss the scientific
      and clinical advancements that will be necessary to develop a competitive cell
      therapy for PD patients.

PMID- 21901585
TI  - Cell-based therapy for neural disorders--anticipating challenges.
AB  - Neurological syndromes, such as Alzheimer's disease, Parkinson's disease,
      multiple sclerosis, Huntington's disease, amyotrophic lateral sclerosis, and
      lysosomal storage disorders, such as Battens disease, are devastating because
      they result in increasing loss of cognitive and physical function. Sadly, no
      drugs are currently available to halt their progression. The relative paucity of
      curative approaches for these and other conditions of the nervous system have led
      to a widespread evaluation of alternative treatment modalities including cell
      based interventions. Several cell types have been tested successfully in animal
      models where safety and efficacy have been demonstrated. Early clinical trials
      have also been initiated in humans, and some have shown a degree of success
      albeit on a more limited scale than in animal experiments. Recent demonstrations
      that pluripotent stem cells, such as embryonic stem cells and induced pluripotent
      stem cells, can differentiate into a variety of specific neural phenotypes has
      stimulated worldwide enthusiasm for developing cell-based intervention of
      neurological disease. Indeed, several groups are preparing investigational new
      drug applications to treat disorders as diverse as macular degeneration,
      lysosomal storage diseases, and Parkinson's disease. It is noteworthy that cell
      replacement therapies for neurological conditions face key challenges, some of
      which are unique, because of the development and organization of the nervous
      system, its metabolism, and connectivity. Choice of the cell (or cells), the
      process of manufacturing them, defining the delivery pathway, developing and
      testing in an appropriate preclinical model, selecting a patient population, and
      visualizing and following or monitoring patients all pose specific issues as
      related to the central and peripheral nervous systems. In this review, we address
      a myriad of challenges that are solvable, but require careful planning and
      attention to the special demands of the human nervous system.

PMID- 21901589
TI  - Reverse phase protein microarrays for clinical applications.
AB  - Phosphorylated proteins represent one of the most important constituents of the
      proteome and are under intense analysis by the biotechnology and pharmaceutical
      industry because of their central role for cellular signal transduction. Indeed,
      alterations in cellular signaling and control mechanisms that modulate signal
      transduction, functionally underpin most human cancers today. Beyond their
      central role as the causative components of tumorigenesis, these proteins have
      become an important research focus for discovery of predictive and prognostic
      biomarkers. Consequently, these pathway constituents comprise a powerful
      biomarker subclass whereby the same analyte that provides prediction and/or
      prognosis is also the drug target itself: a theranostic marker. Reverse phase
      protein microarrays have been developed to generate a functional patient-specific
      circuit "map" of the cell signaling networks based directly on cellular analysis
      of a biopsy specimen. This patient-specific circuit diagram provides key
      information that identifies critical nodes within aberrantly activated signaling
      that may serve as drug targets for individualized or combinatorial therapy. The
      protein arrays provide a portrait of the activated signaling network by the
      quantitative analysis of the phosphorylated, or activated, state of cell
      signaling proteins. Based on the growing realization that each patient's tumor is
      different at the molecular level, the ability to measure and profile the ongoing
      phosphoprotein biomarker repertoire provides a new opportunity to personalize
      therapy based on the patient-specific alterations.

PMID- 21901590
TI  - Impact of blocking and detection chemistries on antibody performance for reverse
      phase protein arrays.
AB  - Careful selection of well-qualified antibodies is critical for accurate data
      collection from reverse phase protein arrays (RPPA). The most common way to
      qualify antibodies for RPPA analysis is by Western blotting because the detection
      mechanism is based on the same immunodetection principles. Western blots of
      tissue or cell lysates that result in single bands and low cross-reactivity
      indicate appropriate antibodies for RPPA detection. Western blot conditions used
      to validate antibodies for RPPA experiments, including blocking and detection
      reagents, have significant effects on aspects of antibody performance such as
      cross-reactivity against other proteins in the sample. We have found that there
      can be a dramatic impact on antibody behavior with changes in blocking reagent
      and detection method, and offer an alternative method that allows detection
      reagents and conditions to be held constant in both antibody validation and RPPA
      experiments.

PMID- 21901591
TI  - Phosphoprotein stability in clinical tissue and its relevance for reverse phase
      protein microarray technology.
AB  - Phosphorylated proteins reflect the activity of specific cell signaling nodes in
      biological kinase protein networks. Cell signaling pathways can be either
      activated or deactivated depending on the phosphorylation state of the
      constituent proteins. The state of these kinase pathways reflects the in vivo
      activity of the cells and tissue at any given point in time. As such, cell
      signaling pathway information can be extrapolated to infer which phosphorylated
      proteins/pathways are driving an individual tumor's growth. Reverse phase protein
      microarrays (RPMAs) are a sensitive and precise platform that can be applied to
      the quantitative measurement of hundreds of phosphorylated signal proteins from a
      small sample of tissue. Pre-analytical variability originating from tissue
      procurement and preservation may cause significant variability and bias in
      downstream molecular analysis. Depending on the ex vivo delay time in tissue
      processing, and the manner of tissue handling, protein biomarkers such as signal
      pathway phosphoproteins will be elevated or suppressed in a manner that does not
      represent the biomarker levels at the time of excision. Consequently, assessment
      of the state of these kinase networks requires stabilization, or preservation, of
      the phosphoproteins immediately post-tissue procurement. We have employed RPMA
      analysis of phosphoproteins to study the factors influencing stability of
      phosphoproteins in tissue following procurement. Based on this analysis we have
      established tissue procurement guidelines for clinical research with an emphasis
      on quantifying phosphoproteins by RPMA.

PMID- 21901592
TI  - Utilization of RNAi to validate antibodies for reverse phase protein arrays.
AB  - Reverse phase protein arrays (RPPAs) emerged as a very useful tool for high
      throughput screening of protein expression in large numbers of small specimen.
      Similar to other protein chemistry methods, antibody specificity is also a major
      concern for RPPA. Currently, testing antibodies on Western blot for specificity
      and applying serial dilution curves to determine signal/concentration linearity
      of RPPA signals are most commonly employed to validate antibodies for RPPA
      applications. However, even the detection antibodies fulfilling both requirements
      do not always give the expected result. Chemically synthesized small interfering
      RNAs (siRNAs) are one of the most promising and time-efficient tools for loss-of
      function studies by specifically targeting the gene of interest resulting in a
      reduction at the protein expression level, and are therefore used to dissect
      biological processes. Here, we report the utilization of siRNA-treated sample
      lysates for the quantification of a protein of interest as a useful and reliable
      tool to validate antibody specificity for RPPAs. As our results indicate, we
      recommend the use of antibodies which give the highest dynamic range between the
      control siRNA-treated samples and the target protein (here: EGFR) siRNA-treated
      ones on RPPAs, to be able to quantify even small differences of protein abundance
      with high confidence.

PMID- 21901586
TI  - [Fibromyalgia].
AB  - Although chronic musculoskeletal pain represents the main symptom of
      fibromyalgia, those affected usually experience many and various accompanying
      symptoms of differing frequency and extent. While symptoms such as non-restful
      sleep, daytime fatigue, impaired memory and concentration, morning stiffness, as
      well as digestive and urination disorders help to establish the diagnosis, they
      represent a particular disease burden on patients, those around them and on the
      social system. Pathogenetic research is focussed increasingly on a central
      dysregulation in pain perception and pain processing, leading to the concept of
      "central sensitisation" as a final common pathway for fibromyalgia and similar
      syndromes. This supports the recommendations for prompt multimodal therapy based
      on pharmaco-, functional and behavioural therapy.

PMID- 21901593
TI  - Antibody-mediated signal amplification for reverse phase protein array-based
      protein quantification.
AB  - Reverse phase protein array (RPPA) techniques allow the quantitative analysis of
      signal transduction events in a high-throughput format. Sensitivity is important
      for RPPA-based detection approaches, since numerous signaling proteins or
      posttranslational modifications are present at low levels. Especially, the
      proteomic analysis of clinical samples exposes its own challenges with respect to
      sensitivity. Antibody-mediated signal amplification (AMSA) is a novel strategy
      relying on sequential incubation steps with fluorescently labeled secondary
      antibodies reactive against each other. AMSA is a simple extension of the
      standard quantification in the near-infrared range and is highly specific and
      robust. In this chapter, we present the amplification protocol and application
      examples for the time-resolved analysis of signaling pathways as well as protein
      profiling of clinical samples.

PMID- 21901594
TI  - Reverse-phase protein lysate microarray (RPA) for the experimental validation of
      quantitative protein network models.
AB  - Theoretical models describing complex biological phenomena have been
      accumulating. However, most of these models have been created with hypothetical
      parameter determination without seeing actual cell reactions. The parameter
      determination requires high-dimensional data monitoring, particularly at the
      protein level. It has been a difficult task to develop the standard model system
      because of the lack of an appropriate validation technique. Reverse-phase protein
      lysate microarray (RPA) is one of the most potent technologies for high
      dimensional proteomic monitoring. Therefore, proteomic monitoring by RPA may
      contribute substantially to develop theoretical protein network models based on
      experimental validation.

PMID- 21901595
TI  - Characterization of kinase inhibitors using reverse phase protein arrays.
AB  - Using the reverse protein array platform in combination with planar waveguide
      technology, which allows detection of proteins in spotted cell lysates with high
      sensitivity in a 96-well microtiter-plate format for growing, treating, and
      lysing cells was shown to be suitable for this approach and indicates the
      usefulness of the technology as a screening tool for characterization of large
      numbers of kinase inhibitors. In this study, we have used reverse protein arrays
      to profile kinase inhibitors in various cellular pathways in order to unravel
      their MoA. Multiplexing and simultaneous analysis of several phospho-proteins
      within the same lysate allows (1) the estimation of inhibitor concentrations
      needed to shut down an entire pathway, (2) the estimation of inhibitor
      selectivity, and (3) the comparison of inhibitors of different kinases within one
      assay. For example, parallel analysis of p-InsR, p-PKB, p-GSK-3, p-MEK, p-ERK,
      and p-S6rp in insulin treated A14 cells allows profiling for inhibitors of the
      InsR, PI3K, PKB, mTor, RAF, and MEK. Selective kinase inhibitors revealed
      different specific inhibitory pattern of the analyzed phospho-read outs.
      Altogether, multiplexed analysis of reverse (phase) protein arrays is a powerful
      tool to characterize kinase inhibitors in a semi-automated low to medium
      throughput assay format.

PMID- 21901596
TI  - Use of formalin-fixed and paraffin-embedded tissues for diagnosis and therapy in
      routine clinical settings.
AB  - Formalin-fixed and paraffin-embedded (FFPE) tissues are used routinely everyday
      in hospitals world-wide for histopathological diagnosis of diseases like cancer.
      Due to formalin-induced cross-linking of proteins, FFPE tissues present a
      particular challenge for proteomic analysis. Nevertheless, there has been recent
      progress for extraction-based protein analysis in these tissues. Novel tools
      developed in the last few years are urgently needed because precise protein
      biomarker quantification in clinical FFPE tissues will be crucial for treatment
      decisions and to assess success or failure of current and future personalized
      molecular therapies. Furthermore, they will help to conceive why only a subset of
      patients responds to individualized treatments. Reverse phase protein array
      (RPPA) is a very promising new technology for quick and simultaneous analysis of
      many patient samples allowing relative and absolute protein quantifications. In
      this chapter, we show how protein extraction from FFPE tissues might facilitate
      the implementation of RPPA for therapy decisions and discuss challenges for
      application of RPPA in clinical trials and routine settings.

PMID- 21901597
TI  - Producing reverse phase protein microarrays from formalin-fixed tissues.
AB  - In most hospitals around the world FFPE (formalin fixed, paraffin embedded)
      tissues have been used for diagnosis and have subsequently been archived since
      decades. This has lead to a sizeable pool of this kind of tissues. Till quite
      recently it was not possible to use this congeries of samples for protein
      analysis, but now several groups described successful protein extraction from
      FFPE tissues. In this chapter, we describe a protein extraction protocol
      established in our laboratory combined with the use of reverse phase protein
      microarray.

PMID- 21901598
TI  - Use of reverse phase protein microarrays to study protein expression in leukemia:
      technical and methodological lessons learned.
AB  - Leukemias are well suited to proteomic profiling by RPPA due to the ready
      accessibility of blasts from the blood or marrow. In this review, we review
      methodological and procedural issues that affect the quality of RPPA data. We
      recommend contact printers that minimize sample quantities and evaporation and
      maximize sample per slide. The impact of sample selection and handling is
      reviewed as well. Protein is best prepared fresh on the date of acquisition as
      cryopreservation changes protein expression levels in some diseases. Rapid
      processing is also required to avoid changes in phosphorylation over time. Sample
      source, blood vs. marrow does not seem to affect results as long as leukemic
      blast enrichment procedures are utilized. The choice of the correct "normal"
      control is important for comparing diseased to "normal" expression. Various means
      of normalizing the data are discussed.

PMID- 21901599
TI  - Antibody microarrays as tools for biomarker discovery.
AB  - The cancer biomarkers field is being enriched by molecular profiling obtained by
      high-throughput approaches. Targeted antibody arrays are strongly contributing to
      the identification of protein cancer -biomarker candidates and functional
      proteomic analyses. Due to their versatility, novel technological and
      experimental design implementations are broadening the applications of antibody
      arrays. However, the cancer biomarker candidates delivered to date using this
      technology are still in their early developmental phase, requiring validation
      with high number of specimens focusing on specific clinical endpoints. Innovative
      strategies multiplexing protein measurements of protein extracts of cultured
      cells, tissue and body fluids using antibody arrays combined with appropriate
      validation approaches are enabling the -discovery of cancer-associated
      biomarkers. This review describes these strategies and cancer biomarker
      candidates reported to date that may assist in the diagnosis, surveillance,
      prognosis, and potentially for predictive and therapeutic purposes for patients
      affected with solid and hematological neoplasias.

PMID- 21901600
TI  - Assessment of antibody specificity using suspension bead arrays.
AB  - With the increasing collection of affinity reagents, their validation in terms of
      functionality and binding specificity becomes a challenge. To match this growing
      need, miniaturized and parallelized platforms have become available to
      corroborate the applicability for a broad range of binder scaffolds. Among the 
      commonly used systems, planar microarrays have been a platform of choice for a
      long time but alternative systems are emerging, of which one is based on color
      coded beads for the creation of arrays in suspension. The latter systems offer to
      perform a two-dimensional multiplexing by now analyzing up to 384 samples against
      up to 500 analytes in a single experiment. While the analyte parameter is
      flexible in terms of its composition, an extended screening can be facilitated
      without the need to set up a microarray production facility.

PMID- 21901601
TI  - Quantitative analysis of phosphoproteins using microspot immunoassays.
AB  - Protein microarrays are an ideal technology platform which allow for a robust and
      standardized profiling of the cellular proteome. Many cellular functions are not
      simply controlled by the presence of certain proteins, especially the propagation
      of external stimuli, which depend on transient post-translational modifications
      that determine whether a protein is in its active or inactive state. Thus,
      complex biological processes require the availability of a sound set of
      quantitative and time-resolved measurements to be understood. For this reason,
      new assay platforms which allow for the investigation of several proteins in
      parallel are necessary. The current best understood mode of cellular regulation
      occurs via phosphorylation and dephosphorylation processes, which are mediated
      via a large panel of kinases and phosphatases. The microspot immunoassay
      technique described here allows for an exact determination of several different
      phosphorylated proteins in parallel, as well as from small sample amounts, and is
      therefore an appropriate system to deepen the understanding of the complex
      regulatory networks implicated in health and disease.

PMID- 21901602
TI  - Robust protein profiling with complex antibody microarrays in a dual-colour mode.
AB  - Antibody microarrays are a multiplexing technique for the analyses of hundreds of
      different analytes in parallel from small sample volumes of few microlitres only.
      With sensitivities in the picomolar to femtomolar range, they are gaining
      importance in proteomic analyses. These sensitivities can be obtained for complex
      protein samples without any pre-fractionation or signal amplification. Also, no
      expensive or elaborate protein depletion steps are needed. As with custom DNA
      microarrays, the implementation of a dual-colour assay adds to assay robustness
      and reproducibility and was therefore a focus of our technical implementation. In
      order to perform antibody microarray experiments for large sets of samples and
      analytes in a robust manner, it was essential to optimise the experimental
      layout, the protein extraction, labelling and incubation as well as data
      processing steps. Here, we present our current protocol, which is used for the
      simultaneous analysis of the abundance of more than 800 proteins in plasma,
      urine, and tissue samples.

PMID- 21901603
TI  - High-throughput studies of protein glycoforms using antibody-lectin sandwich
      arrays.
AB  - The antibody-lectin sandwich arrays (ALSA) is a powerful new tool for
      glycoproteomics research. ALSA enables precise measurements of the glycosylation
      states of multiple proteins captured directly from biological samples. The
      platform can be used in a high-throughput mode with low sample consumption,
      making it well suited to biomarker research exploring glycan alterations on
      specific proteins. This article provides detailed descriptions of the use of
      ALSA, with a particular focus on biomarker research. The preparation and
      selection of antibodies and lectins, the preparation and use of the arrays and
      samples, and special considerations for using the platform for biomarker research
      are covered.

PMID- 21901604
TI  - Microspot immunoassay-based analysis of plasma protein profiles for biomarker
      discovery strategies.
AB  - To expedite the development of personalized medicine, new and reliable biomarkers
      are required to facilitate early diagnosis, to determine prognosis, predict
      response or resistance to different therapies, and to monitor disease progression
      or recurrence. Human body fluids, such as blood, present a promising resource for
      biomarker discovery, in every sense. Microspot immunoassays allow the
      simultaneous quantification of multiple analytes from a minute amount of samples
      in a single measurement. The experimental design of microspot immunoassays is
      based on antibody pairs recognizing different epitopes of the analyte. The first
      antibody is used to capture the analyte from the complex sample, and the second
      antibody is used for detection. As with traditional enzyme-linked immunosorbent
      assays, highly reliable and reproducible results are obtained.

PMID- 21901605
TI  - Recombinant antibodies for the generation of antibody arrays.
AB  - Affinity proteomics, mainly represented by antibody microarrays, has in recent
      years been established as a powerful tool for high-throughput (disease)
      proteomics. The technology can be used to generate detailed protein expression
      profiles, or protein maps, of focused set of proteins in crude proteomes and
      potentially even high-resolution portraits of entire proteomes. The technology
      provides unique opportunities, for example biomarker discovery, disease
      diagnostics, patient stratification and monitoring of disease, and taking the
      next steps toward personalized medicine. However, the process of designing high
      performing, high-density antibody micro- and nanoarrays has proven to be
      challenging, requiring truly cross-disciplinary efforts to be adopted. In this
      mini-review, we address one of these key technological issues, namely, the choice
      of probe format, and focus on the use of recombinant antibodies vs. polyclonal
      and monoclonal antibodies for the generation of antibody arrays.

PMID- 21901606
TI  - Producing protein microarrays from DNA microarrays.
AB  - The development of protein microarrays makes possible interaction-based protein
      assays in miniaturised, multiplexed formats. A major requirement determining
      their uptake and use is the availability and stability of purified, functional
      proteins for immobilisation. With conventional methods, involving individual
      expression and purification of recombinant proteins, the cost of commercial high
      content protein arrays is often found to be prohibitively high. Moreover, due to
      the need for specialised microarray production equipment, custom-made protein
      arrays containing more focussed sets of proteins of interest are also in little
      use. In the DNA array to protein array technology described herein, repeated
      economical printing of protein microarrays from a reusable template DNA
      microarray is performed on demand by cell-free -protein synthesis. Once the
      template DNA microarray has been obtained, protein microarrays are made using
      purely macro-handling procedures, making protein arraying accessible without
      sophisticated microarraying apparatus.

PMID- 21901607
TI  - Cell arrays and high-content screening.
AB  - Endocytosis is one of the most essential cellular processes, which enables cells
      to internalise diverse -material. It is crucial for regulation of receptor
      activity and signalling, cell polarisation, attachment and motility, and a great
      number of other cellular functions. A number of diverse endocytosis pathways are
      described by now; however, their specificity for different cellular cargoes is
      poorly resolved. Only few of endocytosis regulators are well-characterised and
      even less are attributed to the specific cargo. That is very true for the
      integrin endocytosis pathway, which is a key process in cell migration, adhesion,
      and signalling. The recent advent of quantitative fluorescent microscopy and cell
      arrays opened an exciting possibility to systematically characterise molecules
      playing a role in this crucially important process. Here, we describe a
      fluorescent screening microscopy-based assay to identify regulators of integrin
      alpha2 internalisation. The experimental procedure is the best suited for a
      highly parallel screening format, such as cell arrays, albeit can be used in
      single experiments. We provide protocols for sample preparation, fabrication of
      cell arrays and quantification of integrin alpha2 internalisation. The approach
      can be modified to quantify endocytosis of other cargo, and can be used under the
      conditions of knock-down and knock-in as well as for chemical screening.

PMID- 21901608
TI  - Probing calmodulin protein-protein interactions using high-content protein
      arrays.
AB  - The calcium ion (Ca(2+)) is a ubiquitous second messenger that is crucial for the
      regulation of a wide variety of cellular processes. The diverse transient signals
      transduced by Ca(2+) are mediated by intracellular -Ca(2+)-binding proteins.
      Calcium ions shuttle into and out of the cytosol, transported across membranes by
      channels, exchangers, and pumps that regulate flux across the ER, mitochondrial
      and plasma membranes. Calcium regulates both rapid events, such as cytoskeleton
      remodelling or release of vesicle contents, and slower ones, such as
      transcriptional changes. Moreover, sustained cytosolic calcium elevations can
      lead to unwanted cellular activation or apoptosis. Calmodulin represents the most
      significant of the Ca(2+)-binding proteins and is an essential regulator of
      intracellular processes in response to extracellular stimuli mediated by a rise
      in Ca(2+) ion concentration. To profile novel protein-protein interactions that
      calmodulin participates in, we probed a high-content recombinant human protein
      array with fluorophore-labelled calmodulin in the presence of Ca(2+). This
      protein array contains 37,200 redundant proteins, incorporating over 10,000
      unique human proteins expressed from a human brain cDNA library. We describe the
      identification of a high affinity interaction between calmodulin and the single
      pass transmembrane proteins STIM1 and STIM2 that localise to the ER.
      Translocation of STIM1 and STIM2 from the endoplasmic reticulum to the plasma
      membrane is a key step in store operated calcium entry in the cell.

PMID- 21901609
TI  - Protein function microarrays for customised systems-oriented proteome analysis.
AB  - Protein microarrays have many potential applications in the systematic,
      quantitative analysis of protein function. However, simple, reproducible, and
      robust methods for array fabrication that are compatible with the study of large,
      custom collections of potentially unrelated proteins are required. Here, we
      discuss different routes to array fabrication and describe in detail one approach
      in which the purification and immobilisation procedures are combined into a
      single step, significantly simplifying the array fabrication process. We
      illustrate this approach by reference to the creation of an array of human
      protein kinases and discuss methods for assay and data analysis on such arrays.

PMID- 21901610
TI  - Optimized autoantibody profiling on protein arrays.
AB  - Profiling the autoantibody (AAb) repertoire in serum has been routinely used for
      many years for the diagnosis of autoimmune diseases, including rheumatoid
      arthritis, scleroderma, and lupus. In recent years, AAb profiling of cancers has
      become a prominent field in oncology research. Protein arrays enable high
      throughput screening of clinical samples, characterising the serum profile using
      low volumes of samples. This chapter describes the use of a protein array
      comprising 37,200 redundant proteins (containing over 10,000 non-redundant human
      recombinant proteins) for identification of the proteins bound by the antibodies
      in human sera using a test set of serum samples. The proteins identified have the
      potential to be candidate biomarkers. These recombinant proteins are expressed,
      purified, and robotically spotted on microarrays or chips to facilitate the
      screening of additional serum samples with the aim of identifying a candidate
      biomarker or panel of potential biomarkers for applications in disease diagnosis,
      stage, progression, or response to therapy.

PMID- 21901611
TI  - Inkjet printing for the production of protein microarrays.
AB  - A significant proportion of protein microarray researchers would like the arrays
      they develop to become widely used research, screening, validation or diagnostic
      devices. For this to be achievable the arrays must be compatible with high
      throughput techniques that allow manufacturing scale production. In order to
      simplify the transition from laboratory bench to market, Arrayjet have developed
      a range of inkjet microarray printers, which, at one end of the scale, are
      suitable for R&D and, at the other end, are capable of true high-throughput array
      output. To maintain scalability, all Arrayjet microarray printers utilise
      identical core technology comprising a JetSpyderTM liquid handling adaptor, which
      enables automated loading of an industry standard inkjet printhead compatible
      with non-contact on-the-fly printing. This chapter contains a detailed
      explanation of Arrayjet technology followed by a historical look at the
      development of inkjet technologies for protein microarray production. The method
      described subsequently is a simple example of an antibody array printed onto
      nitrocellulose-coated slides with specific detection with fluorescently labelled
      IgG. The method is linked to a notes section with advice on best practice and
      sources of useful information for protein microarray production using inkjet
      technology.

PMID- 21901612
TI  - Impact of substrates for probe immobilization.
AB  - Protein chips are becoming a key technology in proteomic research and medical
      diagnostics. Surface chemistry for immobilization of proteins forms the basis for
      assay design and determines the properties of protein microarrays. Optimal
      substrates provide a homogeneous environment for probes, preventing loss of
      biological activity and unspecific adsorption. Numerous immobilization
      approaches, based on covalent binding, affinity, or adsorption, have been
      proposed thus far, and these represent the toolbox for choosing optimized
      strategies for each individual application.

PMID- 21901613
TI  - Contact printing of protein microarrays.
AB  - A review is provided of contact-printing technologies for the fabrication of
      planar protein microarrays. The key printing performance parameters for creating
      protein arrays are reviewed. Solid pin and quill pin technologies are described
      and their strengths and weaknesses compared.

PMID- 21901614
TI  - Nuclear barrier hypothesis of aging as mechanism for trade-off growth to
      survival.
AB  - When the aging-dependent cellular behaviors toward growth factors and toxic
      stress have been analyzed, the perinuclear accumulation of the activated signals,
      either mitogenic or apoptotic, has been observed, suggesting the aging-dependent
      inefficiency of the nucleocytoplasmic trafficking of the signals. Thereby, it
      would be natural to assume the operation of the functional nuclear barrier in
      aging-dependent manner, which would be designated as "Park and Lim's Barrier."
      And for the ultimate transcriptional factor for these aging-dependent changes of
      the functional nuclear barrier, Sp1 transcriptional factor has been suggested to
      be the most probable candidate. This novel mechanism of aging-dependent operation
      of the functional nuclear barrier is proposed as the ultimate checking mechanism
      for cellular protection against toxic environment and the general mechanism for
      the trade-off growth to survival in aging.

PMID- 21901615
TI  - Establishment of cell lines from the human middle and inner ear epithelial cells.
AB  - The middle ear infection is the most common childhood infection. In order to
      elucidate the cell and molecular mechanisms involved in bacterial recognition and
      innate immune response, we have established a stable human middle ear cell line,
      which has contributed to the current knowledge concerning the molecular
      pathogenesis of the middle ear infection. The inner ear, a sensory organ
      responsible for hearing and balance, is filled with inner ear fluid, and
      disturbance of the fluid homeostasis results in dizziness and hearing impairment.
      It has been suggested that the endolymphatic sac (ES) may play a critical role in
      the fluid homeostasis of the inner ear. We have established a stable human ES
      cell line and are undertaking cell and molecular characterization of this cell
      line.

PMID- 21901616
TI  - Cellular systems for studying human oral squamous cell carcinomas.
AB  - The human oral squamous epithelium plays an important role in maintaining a
      barrier function against mechanical, physical, and pathological injury. However,
      the self-renewing cells residing on the basement membrane of the epithelium can
      give rise to oral squamous cell carcinomas (OSCC), now the sixth most common
      cancer in the developed world, which is still associated with poor prognosis.
      This is due, in part, to the limited availability of well-defined culture systems
      for studying oral epithelial cell biology, which could advance our understanding
      of the molecular basis of OSCC. Here, we describe methods to successfully isolate
      large cultures of human oral epithelial cells and fibroblasts from small pieces
      of donor tissues for use in techniques such as three-dimensional cultures and
      animal grafts to validate genes suspected of playing a role in OSCC development
      and progression. Finally, the use of isolated oral epithelial cells in generating
      iPS cells is discussed which holds promise in the field of oral regenerative
      medicine.

PMID- 21901617
TI  - Heterotopic ossification following musculoskeletal trauma: modeling stem and
      progenitor cells in their microenvironment.
AB  - Heterotopic ossification (HO), characterized by the formation of mature bone in
      the soft tissues, is a complication that can accompany musculoskeletal injury,
      and it is a frequent occurrence within the military population that has
      experienced orthopaedic combat trauma. The etiology of this disease is largely
      unknown. Our laboratory has developed strategies to investigate the cellular and
      molecular events leading to HO using clinical specimens that were obtained during
      irrigation and debridement of musculoskeletal injuries. Our approach enables to
      study (1) the cell types that are responsible for pathological transformation and
      ossification, (2) the cell- and tissue-level signaling that induces the
      pathologic transformation, and (3) the effect of extracellular matrix topography
      and force transduction on HO progression. In this review, we will report on our
      findings in each of these aspects of HO etiology and describe our efforts to
      recapitulate our findings in an animal model for traumatic HO.

PMID- 21901618
TI  - Comparative proteomic analysis of mesenchymal stem cells derived from human bone
      marrow, umbilical cord and placenta: implication in the migration.
AB  - Umbilical cord (UC) and placenta (P) have been suggested as alternatives to bone
      marrow (BM) as sources of mesenchymal stem cells (MSC) for cell therapy, with
      both UC- and P-MSC possess immunophenotypic and functional characteristics
      similar to BM-MSC. However, under defined conditions, the migration capacity of
      BM- and P-MSC was found to be 5.9- and 3.2-folds higher than that of UC-MSC,
      respectively. By the use of 2-DE and combined MS and MS/MS analysis, six
      differentially expressed proteins were identified among these MSC samples, with
      five of them known to be involved in cell migration as migration enhancing or
      inhibiting proteins. Interestingly, the expression levels of those proteins
      reflect perfectly the migration capacity of corresponding MSC, which is also
      proved by in vitro overexpression and silencing techniques. Our study indicates
      that a bunch of migration-related proteins are pivotal in governing the migration
      capacity of MSC.

PMID- 21901619
TI  - Novel human prostate epithelial cell culture models for the study of
      carcinogenesis and of normal stem cells and cancer stem cells.
AB  - Research into the mechanisms of prostate cancer progression has been limited by
      the lack of suitable in vitro systems. A hurdle in understanding the molecular
      genetic changes in prostate cancer has been the difficulty in establishing
      premalignant lesions and primary prostate tumors as in vitro cell cultures.
      Primary prostate epithelial cells grow for a finite life span and then senesce.
      Immortalization is defined by continuous growth of otherwise senescing cells and
      is believed to represent an early stage in tumor progression. To examine these
      early stages, we and others have developed in vitro models of prostate epithelial
      cell immortalization. Generation of primary human prostate epithelial (HPE) cells
      has been achieved using the serum-free condition. Retrovirus containing human
      telomerase reverse transcriptase (hTERT) was successfully used for the
      immortalization of primary HPE cells. Putative stem cell markers CD133 and CXCR4
      were further identified in hTERT-immortalized primary nonmalignant and malignant
      tumor-derived HPE lines. In addition, an hTERT-immortalized nonmalignant HPE cell
      were found to retain the properties of multipotent stem cells. These in vitro
      prostate cell culture models should be useful for the study of carcinogenesis and
      of normal and cancer stem cells. Prostate cancer is the most common male cancer
      in the Western World and second leading cause of male cancer death in the United
      States [1]. The therapy most widely used against advanced disease is androgen
      ablation and, initially, it almost always produces objective clinical responses.
      However, most patients eventually relapse with ablation-resistant prostate cancer
      and develop metastatic disease; currently, there is no treatment that will cure
      progressive hormone-refractory metastatic prostate cancer. The mechanisms of
      progression of prostate cancer have been extensively studied, yet are poorly
      understood. One of the concepts that has been evolved is that cancer arises from
      the neoplastic transformation of normal prostate epithelial stem cells or transit
      amplifying cells. Understanding normal stem cells and cancer stem cells (CSCs)
      may provide insight into the origin of and new therapeutics for prostate cancer.
      However, research in this field is limited by the lack of suitable in vitro
      systems.

PMID- 21901621
TI  - Role of epigenetics in cancer initiation and progression.
AB  - The epigenome which comprises DNA methylation, histone modifications, chromatin
      structures and non-coding RNAs controls gene expression patterns. In cancer
      cells, there are aberrant changes in the epigenome. The question in cancer
      epigenetics is that whether these changes are the cause of cell transformation,
      or rather the consequence of it. We will discuss the epigenetic phenomenon in
      cancer, as well as the recent interests in the epigenetic reprogramming events,
      and their implications in the cancer stem cell theory. We will also look at the
      progression of cancers as they become more aggressive, with focus on the role of
      epigenetics in tumor metastases exemplified with the urokinase plasminogen
      activator (uPA) system. Last but not least, with therapeutics intervention in
      mind, we will highlight the importance of balance in the design of epigenetic
      based anti-cancer therapeutic strategies.

PMID- 21901620
TI  - Prostate tumor cell plasticity: a consequence of the microenvironment.
AB  - During each step of prostate cancer metastasis, cancer displays phenotypic
      plasticity that is associated with the expression of both epithelial and
      mesenchymal properties or an epithelial to mesenchymal transition. This
      phenotypic transition is typically in response to microenvironment signals and is
      the basis for basic cancer cell survival (e.g. motility and invasion versus
      proliferation). In this review we discuss the loss and gain of E-cadherin
      expression as a marker of tumor plasticity throughout the steps of metastasis,
      and particularly focus on dynamic tumor-stromal interaction that induce a cancer
      cell-associated mesenchymal to epithelial reverting transition in the bone and
      liver microenvironments.

PMID- 21901622
TI  - Cancer stem cells, models of study and implications of therapy resistance
      mechanisms.
AB  - There is now compelling evidence for tumour initiating or cancer stem cells
      (CSCs) in human cancers. The current evidence of this CSC hypothesis, the CSC
      phenotype and methods of identification, culture and in vitro modelling will be
      presented, with an emphasis on prostate cancer. Inherent in the CSC hypothesis is
      their dual role, as a tumour-initiating cell, and as a source of treatment
      resistant cells; the mechanisms behind therapeutic resistance will be discussed.
      Such resistance is a consequence of the unique CSC phenotype, which differs from
      the differentiated progeny, which make up the bulk of a tumour. It seems that to
      target the whole tumour, employing traditional therapies to target bulk
      populations alongside targeted CSC-specific drugs, provides the best hope of
      lasting treatment or even cure.

PMID- 21901623
TI  - The role of the basal stem cell of the human breast in normal development and
      cancer.
AB  - MCF-10F, an ERalpha negative human breast epithelial cell line derived from
      normal breast tissue, is able to form ductal structures in a tridimensional
      collagen matrix system. MCF-10F cells that are estrogen transformed (trMCF cells)
      progressively express phenotypes of in vitro cell transformation, including
      colony formation in agar methocel and loss of the ductulogenic capacity.
      Selection of these trMCF cells for invasiveness identified cells (bcMCF) that
      formed tumors in severe combined immunodeficient mice. The cell lines derived
      from those tumors (caMCF) were poorly differentiated ER, PR, and ERBB2 negative
      adenocarcinomas. These characteristics are similar to the human basal cell-like
      carcinomas. This in vitro-in vivo model demonstrates the importance of the basal
      cell type as a stem cell that reconstitutes the branching pattern of the breast
      and that is also target of a carcinogenic insult leading to transformation and
      cancer.

PMID- 21901625
TI  - Parathyroid hormone related protein (PTHrP) in tumor progression.
AB  - Parathyroid hormone-related protein (PTHrP) is widely expressed in fetal and
      adult tissues and is a key regulator for cellular calcium transport and smooth
      muscle cell contractility, as well as a crucial control factor in cell
      proliferation, development and differentiation. PTHrP stimulates or inhibits
      apoptosis in an autocrine/paracrine and intracrine fashion, and is particularly
      important for hair follicle and bone development, mammary epithelial development
      and tooth eruption. PTHrP's dysregulated expression has traditionally been
      associated with oncogenic pathologies as the major causative agent of malignancy
      associated hypercalcemia, but recent evidence revealed a driving role in skeletal
      metastasis progression. Here, we demonstrate that PTHrP is also closely involved
      in breast cancer initiation, growth and metastasis through mechanisms separate
      from its bone turnover action, and we suggest that PTHrP as a facilitator of
      oncogenes would be a novel target for therapeutic purposes.

PMID- 21901624
TI  - Breast cancer subtypes: two decades of journey from cell culture to patients.
AB  - Recent molecular profiling has identified six major subtypes of breast cancers
      that exhibit different survival outcomes for patients. To address the origin of
      different subtypes of breast cancers, we have now identified, isolated, and
      immortalized (using hTERT) mammary stem/progenitor cells which maintain their
      stem/progenitor properties even after immortalization. Our decade long research
      has shown that these stem/progenitor cells are highly susceptible to oncogenesis.
      Given the emerging evidence that stem/progenitor cells are precursors of cancers
      and that distinct subtypes of breast cancer have different survival outcome,
      these cellular models provide novel tools to understand the oncogenic process
      leading to various subtypes of breast cancers and for future development of novel
      therapeutic strategies to treat different subtypes of breast cancers.

PMID- 21901626
TI  - Mechanism of radiation carcinogenesis: role of the TGFBI gene and the
      inflammatory signaling cascade.
AB  - Using an immortalized human bronchial epithelial cell line, we showed previously
      that the transforming growth factor beta-induced (TGFBI) gene was consistently
      downregulated by six- to sevenfold among radiation-induced tumorigenic human
      cells when compared with controls. Transfection of TGFBI gene into tumor cells
      resulted in a significant reduction in tumor growth as well as in vitro anchorage
      independent growth. The observations that TGFBI knock-out animals showed
      increased spontaneous tumor incidence and chemically induced tumors highlight the
      suppressive nature of the gene. There is evidence that extranuclear/extracellular
      targets are important in low-dose radiation response and that the cyclo-oxygenase
      2 signaling pathway mediates the process. The involvement of NFkappaB-dependent
      cytokines and the resultant inflammatory response works in concert with in
      modulating radiation-induced bronchial carcinogenesis.

PMID- 21901627
TI  - Histone deacetylase inhibitor: antineoplastic agent and radiation modulator.
AB  - Inhibitors of histone deacetylases (HDACs) have emerged as a new class of
      anticancer agents based on their actions in cancer cell growth and cell cycle
      arrest, terminal differentiation, and apoptosis. Previously, we rationally
      designed and developed a new class of hydroxamide- and mercaptoacetamide-bearing
      HDAC inhibitors. A subset of these inhibitors exhibited chemo-radiation
      sensitizing properties in various human cancer cells. Furthermore, some HDAC
      inhibitors protected normal cells from radiation-induced damage and extended the
      survival of mice following total body exposure to lethal dose radiation.
      Pathological analyses revealed that intestinal and bone marrow cellularities
      recovered significantly from radiation-induced damage by structural compartments
      restoration, suggesting the mechanism of action of these HDAC inhibitors. These
      findings support the hypothesis that epigenetic regulation may play a crucial
      role in the functional recovery of normal tissues from radiation injuries.

PMID- 21901628
TI  - Human fibroblasts for large-scale "omics" investigations of ATM gene function.
AB  - ATM (gene mutated in ataxia-telangiectasia) is a critical central component of
      the pleiotropic responses of cells to ionizing radiation-induced stress. To gain
      insight into molecular mechanisms and to enhance our understanding of ATM
      functions, we have advanced a human model cell system, derived from genetically
      defined immortal fibroblasts, and we have applied high-throughput genomic,
      proteomic and metabolomic technologies for a systems level analysis. The cellular
      characterizations reported here provide the background for application of a
      systems analysis to integrate transcription, post-translational modifications and
      metabolic activity induced by exposure of cells to ionizing radiation. We present
      here a summary of the derivation and characterization of cells comprising this
      model cell system and review applications of this model to systems analysis of
      ATM functions.

PMID- 21901629
TI  - Malignant transformation of human skin fibroblasts by two alternative pathways.
AB  - We developed a telomerase-positive, infinite life span human fibroblast cell
      strain (MSU-1.0) by transfection of a v-MYC oncogene and spontaneous over
      expression of transcription factors SP1/SP3. Loss of expression of p14(ALT) and
      enhanced expression of SPRY2 gave rise to the MSU-1.1 cell strain. Unlike MSU-1.0
      cells, the MSU-1.1 cells can be malignantly transformed by expression of N
      RAS(LYS61) or H-Ras(v12) oncoproteins (driven by their original promoters) and
      expression of a SRC-family protein, v-FES. MSU-1.1 cells can also be malignantly
      transformed by high expression of these RAS oncogenes or the v-K-RAS oncogene.
      PDGF-B transformed MSU-1.1 cells give rise to benign tumors (fibromas) in athymic
      mice. A second route to malignant transformation of the MSU-1.1 cells involves
      loss of functional TP53 protein by carcinogen treatment and loss of expression of
      wild type p16(INK). These studies indicate 6-8 "hits" are required to activate
      the oncogenes and inactivate the suppressor genes we identified.

PMID- 21901630
TI  - A novel tumor suppressor, REIC/Dkk-3 gene identified by our in vitro
      transformation model of normal human fibroblasts works as a potent therapeutic
      anti-tumor agent.
AB  - Reduced Expression in Immortalized Cell (REIC) was cloned by subtractive
      hybridization method as a gene whose expression is reduced in many human
      immortalized and neoplastic tumor cells. The REIC, when over-expressed by an
      adenovirus (Ad-REIC), exhibited a dramatic therapeutic effect on a wide variety
      of human cancers through a mechanism triggered by ER-stress-mediated JNK
      activation. In addition to this direct effect on cancer cells, Ad-REIC exerted
      another cytotoxicity on human cancers, an indirect host-mediated effect due to
      overproduction of IL-7 by mis-targeted normal cells. This "one-bullet two-arms"
      finding may lead to a powerful new therapeutic approach to the treatment of human
      cancers.

PMID- 21901631
TI  - Mycobacterial infections in adult patients with hematological malignancy.
AB  - We retrospectively analyzed the clinical and microbiological characteristics of
      adult patients with hematological malignancy and nontuberculous mycobacteria
      (NTM) infections from 2001 to 2010. During the study period, 50 patients with
      hematological malignancy and tuberculosis (TB) were also evaluated. Among 2,846
      patients with hematological malignancy, 34 (1.2%) patients had NTM infections.
      Mycobacterium avium-intracellulare complex (13 patients, 38%) was the most
      commonly isolated species, followed by M. abscessus (21%), M. fortuitum (18%),
      and M. kansasii (18%). Twenty-six patients had pulmonary NTM infection and eight
      patients had disseminated disease. Neutropenia was more frequently encountered
      among patients with disseminated NTM disease (p = 0.007) at diagnosis than among
      patients with pulmonary disease only. Twenty-five (74%) patients received
      adequate initial antibiotic treatment. Five of the 34 patients died within 30
      days after diagnosis. Cox regression multivariate analysis showed that chronic
      kidney disease (p = 0.017) and neutropenia at diagnosis (p = 0.032) were
      independent prognostic factors of NTM infection in patients with hematological
      malignancy. Patients with NTM infection had higher absolute neutrophil counts at
      diagnosis (p = 0.003) and a higher 30-day mortality rate (15% vs. 2%, p = 0.025)
      than TB patients. Hematological patients with chronic kidney disease and febrile
      neutropenia who developed NTM infection had significant worse prognosis than
      patients with TB infection.

PMID- 21901633
TI  - Antistaphylococcal activity of Inula helenium L. root essential oil: eudesmane
      sesquiterpene lactones induce cell membrane damage.
AB  - The purpose of this study was to investigate the inhibitory/bactericidal activity
      and cell membrane effects of the hydrodistilled essential oil of Inula helenium
      L. roots against Staphylococcus aureus. Additionally, detailed chemical
      investigation was done in order to pinpoint the most active oil constituents and
      also the parts of these molecules responsible for their antimicrobial effect. The
      minimum inhibitory concentration (MIC) and minimum bactericidal concentration
      (MBC) were determined using the broth microdilution method. The membrane-active
      nature of this oil was investigated by measuring the culture turbidity, leakage
      of phosphates, and 260-nm-absorbing material, together with lysis of the exposed
      cells. Finally, the effect of the oil on the cells was visualized using scanning
      electron microscopy (SEM). The chemical composition of the essential oil was
      analyzed using gas chromatography-mass spectrometry (GC-MS) and preparative
      medium-pressure liquid chromatography (MPLC). Chemical modification of the oil
      was performed using catalytic hydrogenation (H(2), Pd/C) and reduction with
      NaBH(4). The MIC and MBC values were 0.01 MUl mL(-1) and 0.02 MUl mL(-1),
      respectively. Membrane damage was demonstrated through increased permeability
      (phosphates and nucleic acid leakage), followed by lysis of the exposed cells,
      captured on SEM images. The most active constituents were alantolactone,
      isoalantolactone, and diplophyllin. The essential oil showed very potent
      antistaphylococcal activity, with obvious membrane-damaging effects.
      Sesquiterpene lactones were found to be the most active principles of the oil,
      whose eudesmane core olefinic bonds, along with the alpha,beta-methylene-lactone
      ring, are essential structural parts responsible for the exhibited antimicrobial
      activity.

PMID- 21901632
TI  - Human African trypanosomiasis in endemic populations and travellers.
AB  - Human African trypanosomiasis (HAT) or sleeping sickness is caused by the
      protozoan parasites Trypanosoma brucei (T.b.) gambiense (West African form) and
      T.b. rhodesiense (East African form) that are transmitted by the bite of the
      tsetse fly, Glossina spp.. Whereas most patients in endemic populations are
      infected with T.b. gambiense, most tourists are infected with T.b. rhodesiense.
      In endemic populations, T.b. gambiense HAT is characterized by chronic and
      intermittent fever, headache, pruritus, and lymphadenopathy in the first stage
      and by sleep disturbances and neuro-psychiatric disorders in the second stage.
      Recent descriptions of the clinical presentation of T.b. rhodesiense in endemic
      populations show a high variability in different foci. The symptomatology of
      travellers is markedly different from the usual textbook descriptions of African
      HAT patients. The onset of both infections is almost invariably an acute and
      febrile disease. Diagnosis and treatment are difficult and rely mostly on old
      methods and drugs. However, new molecular diagnostic technologies are under
      development. A promising new drug combination is currently evaluated in a phase 3
      b study and further new drugs are under evaluation.

PMID- 21901634
TI  - Molecular characterization of Streptococcus pneumoniae invasive serotype 19A
      isolates from adults in two Spanish regions (1994-2009).
AB  - From 1994 to 2009, the incidence of invasive serotype 19A pneumococci isolated
      from adults in Barcelona and San Sebastian almost doubled every 4 years.
      Genotyping of the 167 invasive isolates studied showed serotype 19A to be highly
      heterogeneous, with 35 different sequence types (STs) and a different clonal
      structure in each region and time period. Multiresistance, defined as non
      susceptibility to three or more antimicrobials, was found in 86 (51.5%) isolates.
      The most frequent ST was the multidrug-resistant ST276 (n = 28), which is a
      single-locus variant of the Denmark(14)-ST230 global clone. The ST276 clone, only
      present in San Sebastian before 2001, was successfully disseminated from 2002 in
      both cities and was the main contributor to the overall increase of serotype 19A
      infections.

PMID- 21901635
TI  - Viral aetiology of influenza-like illness in Belgium during the influenza
      A(H1N1)2009 pandemic.
AB  - The purpose of this investigation was to determine the proportion of influenza
      like illness (ILI) attributable to specific viruses during the influenza
      A(H1N1)2009 pandemic and to describe the demographic and clinical characteristics
      of ILI due to respiratory viruses in Belgium. Nasopharyngeal swabs were collected
      from ILI patients by general practitioners (GPs) and paediatricians (PediSurv)
      and analysed for viruses. Of 139 samples collected from children <5 years of age
      by PediSurv, 86 were positive, including 28 influenza (20%), 27 respiratory
      syncytial virus (RSV) (19%), 21 rhinovirus (17%), 12 human metapneumovirus (hMPV)
      (9%) and ten parainfluenza virus (PIV) (7%). Of 810 samples received from GPs,
      426 were influenza (53%). Of 312 influenza-negative samples, 41 were rhinovirus
      (13%), 13 RSV (4%), 11 PIV (4%) and three hMPV (1%). Influenza mostly affected
      the 6-15 years old age group. Other respiratory viruses were commonly detected in
      the youngest patients. Similar clinical symptoms were associated with different
      respiratory viruses. Influenza A(H1N1)2009 was the most detected virus in ILI
      patients during the 2009-2010 winter, suggesting a good correlation between ILI
      case definition and influenza diagnosis. However, in children under 5 years of
      age, other respiratory viruses such as RSV were frequently diagnosed.
      Furthermore, our findings do not suggest that the early occurrence of the
      influenza A(H1N1)2009 epidemic impacted the RSV epidemic in Belgium.

PMID- 21901636
TI  - Differentiation between Shigella, enteroinvasive Escherichia coli (EIEC) and
      noninvasive Escherichia coli.
AB  - Shigella causes bacillary dysentery and is classified into four species based on
      their antigen characteristics. This classification does not reflect genetic
      relatedness; in fact, Shigella species are so related to Escherichia coli , they
      should be classified as one distinctive species in the genus Escherichia. The
      differentiation of Shigella and E. coli is even more complicated with the
      description of enteroinvasive E. coli (EIEC). EIEC are strains that possess some
      of the biochemical characteristics of E. coli and have the ability to cause
      dysentery using the same method of invasion as Shigella does. Sequencing of
      multiple housekeeping genes indicates that EIEC is more related to Shigella than
      to non-invasive E. coli. Shigella and EIEC evolved from the same ancestor and
      form a single pathovar within E. coli. Shigella and EIEC could be separated from
      other E. coli by a PCR targeting the ipaH-gene; this is a multicopy gene
      exclusively found in all Shigella and EIEC. It is possible to differentiate
      Shigella and all E. coli, including EIEC, by using multiple tests, including ipaH
      gene PCR, physiological and biochemical typing and serological typing. Based on
      literature study, a key is designed for daily use in diagnostic laboratories to
      identify Shigella and all E. coli.

PMID- 21901637
TI  - Dealing with initial inconclusive serological results for chronic Chagas disease
      in clinical practice.
AB  - Most guidelines for Chagas disease recommend the performance of two serological
      tests in order to detect it. However, inconclusive results may arise from this
      strategy. The aim was to describe whether serological follow-up together with the
      patient's clinical characteristics could clarify the outcome of patients with
      initial inconclusive test results. In this retrospective case series, all results
      of Chagas disease serological tests and outpatient visits recorded from 2004 to
      2008 were screened for inclusion. The inclusion criterion was clinical suspicion
      of chronic Chagas disease and the exclusion criteria were previous diagnosis of
      Chagas disease, suspicion of acute Chagas disease, and serological tests with no
      corresponding medical evaluation. A total of 1,732 patients were analyzed.
      Chronic Chagas disease prevalence was 21.1%. After the initial set of serological
      tests, 2.9% of patients had inconclusive test results. Most of these patients had
      definite diagnosis after clinical follow-up and the repetition of serological
      tests in a new blood sample. Loss to follow-up while partaking in the diagnostic
      investigation reached 17.7%. The prevalence of initial inconclusive serological
      tests for chronic Chagas disease is low. Clinical evaluations and follow-up
      clarify the definite diagnosis. Noncompliance to follow-up is a frequent problem.
      Strategies to reduce inconclusive results and noncompliance are discussed.

PMID- 21901638
TI  - High pentraxin-3 plasma levels associate with thrombocytopenia in acute Puumala
      hantavirus-induced nephropathia epidemica.
AB  - Our aim was to investigate whether plasma levels of the long pentraxin-3 (PTX3)
      associate with the severity of Puumala hantavirus-induced nephropathia epidemica
      (NE). Sixty-one prospectively identified consecutively hospitalized NE patients
      were examined. Plasma PTX3, interleukin (IL)-6, terminal complement complex SC5b
      9, complement component C3, C-reactive protein (CRP), creatinine, sodium,
      kynurenine, and tryptophan levels, as well as the blood cell count, were
      determined for up to five consecutive days after hospitalization. Receiver
      operating characteristic (ROC) analysis revealed that the maximum PTX3 level
      >101.6 ng/ml (high PTX3) showed a sensitivity of 71% and a specificity of 89% for
      detecting platelet level <50 * 10(9)/l, with an area under the curve (AUC) value
      of 0.78 (95% confidence interval [CI] 0.63-0.94). High PTX3 level was also
      associated with several other variables reflecting the severity of the disease:
      patients with high PTX3 level had higher maximum blood leukocyte (16.1 vs. 9.7 *
      10(9)/l, p < 0.001), plasma IL-6 (16.9 vs. 9.0 pg/ml, p = 0.007), and creatinine
      (282 vs. 124 MUmol/l, p = 0.007) levels than patients with low maximum PTX3
      level. They also had longer hospital stays (8 vs. 5 days, p = 0.015) compared to
      patients with low PTX3 level. High plasma PTX3 levels are associated with
      thrombocytopenia and the overall severity of NE.

PMID- 21901639
TI  - Differential gene expression of muscle-specific ubiquitin ligase MAFbx/Atrogin-1
      and MuRF1 in response to immobilization-induced atrophy of slow-twitch and fast
      twitch muscles.
AB  - We examined muscle-specific ubiquitin ligases MAFbx/Atrogin-1 and MuRF1 gene
      expression resulting from immobilization-induced skeletal muscle atrophy of slow
      twitch soleus and fast-twitch plantaris muscles. Male C57BL/6 mice were subjected
      to hindlimb immobilization, which induced similar percentage decreases in muscle
      mass in the soleus and plantaris muscles. Expression of MAFbx/Atrogin-1 and MuRF1
      was significantly greater in the plantaris muscle than in the soleus muscle
      during the early stage of atrophy. After a 3-day period of atrophy, total FOXO3a
      protein level had increased in both muscles, while phosphorylated FOXO3a protein
      had decreased in the plantaris muscle, but not in the soleus muscle. PGC-1alpha
      protein expression did not change following immobilization in both muscles, but
      basal PGC-1alpha protein in the soleus was markedly higher than that in plantaris
      muscles. These data suggest that although soleus and plantaris muscles atrophied
      to a similar extent and that muscle-specific ubiquitin protein ligases (E3) may
      contribute more to the atrophy of fast-twitch muscle than to that of slow-twitch
      muscle during immobilization.

PMID- 21901640
TI  - Sarcomere length-dependent Ca2+ activation in skinned rabbit psoas muscle fibers:
      coordinated regulation of thin filament cooperative activation and passive force.
AB  - In skeletal muscle, active force production varies as a function of sarcomere
      length (SL). It has been considered that this SL dependence results simply from a
      change in the overlap length between the thick and thin filaments. The purpose of
      this study was to provide a systematic understanding of the SL-dependent increase
      in Ca(2+) sensitivity in skeletal muscle, by investigating how thin filament "on
      off" switching and passive force are involved in the regulation. Rabbit psoas
      muscles were skinned, and active force measurements were taken at various Ca(2+)
      concentrations with single fibers, in the short (2.0 and 2.4 MUm) and long (2.4
      and 2.8 MUm) SL ranges. Despite the same magnitude of SL elongation, the SL
      dependent increase in Ca(2+) sensitivity was more pronounced in the long SL
      range. MgADP (3 mM) increased the rate of rise of active force and attenuated SL
      dependent Ca(2+) activation in both SL ranges. Conversely, inorganic phosphate
      (Pi, 20 mM) decreased the rate of rise of active force and enhanced SL-dependent
      Ca(2+) activation in both SL ranges. Our analyses revealed that, in the absence
      and presence of MgADP or Pi, the magnitude of SL-dependent Ca(2+) activation was
      (1) inversely correlated with the rate of rise of active force, and (2) in
      proportion to passive force. These findings suggest that the SL dependence of
      active force in skeletal muscle is regulated via thin filament "on-off" switching
      and titin (connectin)-based interfilament lattice spacing modulation in a
      coordinated fashion, in addition to the regulation via the filament overlap.

PMID- 21901641
TI  - Intermittent arm ischemia induces vasodilatation of the contralateral upper limb.
AB  - Intermittent arm ischemia before percutaneous coronary intervention induces
      remote ischemic preconditioning (RIPC) and attenuates myocardial injury in
      patients with myocardial infarction. Several studies have shown that intermittent
      arm ischemia increases coronary flow and is related to autonomic nerve system.
      The aim of this study was to determine whether intermittent arm ischemia induces
      vasodilatation of other arteries and to assess changes in the autonomic nerve
      system during intermittent arm ischemia in humans. We measured change in the
      right brachial artery diameter during intermittent left arm ischemia through
      three cycles of 5-min inflation (200 mmHg) and 5-min deflation of a blood
      pressure cuff using a 10-MHz linear array transducer probe in 20 healthy
      volunteers. We simultaneously performed power spectral analysis of heart rate.
      Ischemia-reperfusion of the left arm significantly dilated the right brachial
      artery time-dependently, resulting in a 3.2 +/- 0.4% increase after the 3rd
      cycle. In the power spectral analysis of heart rate, the high-frequency domain
      (HF), which is a marker of parasympathetic activity, was significantly higher
      after the 3rd cycle of ischemia-reperfusion than baseline HF (P = 0.02).
      Intermittent arm ischemia was accompanied by vasodilatation of another artery and
      enhancement of parasympathetic activity. Those effects may play an important role
      in the mechanism of RIPC.

PMID- 21901643
TI  - Independent risk factors for cardiac operations in adults with congenital heart
      disease: a retrospective study of 543 operations for 500 patients.
AB  - Adults with congenital heart disease (CHD) are an increasing population requiring
      cardiac operations. To date, the perioperative risk factors for this group have
      not been identified. This study aimed to identify clinical, morphologic, and
      hemodynamic risk factors for an adverse outcome. This study retrospectively
      analyzed a cohort of 500 patients (ages >16 years) who underwent 543 operations
      between January 2004 and December 2008 at a single center. The composite end
      point of an adverse outcome was in-hospital death, a prolonged intensive care
      exceeding 4 days, or both. The composite end point was reached by 253 of the
      patients (50.6%). Of the 500 patients, 13 (2.6%) died within 30 days after the
      operation. After logistic regression analysis, the following eight items remained
      significant: male gender (P = 0.003; odds ratio [OR] 1.8; 95% confidence interval
      [CI] 1.2-2.6), cyanosis (P > 0.006; OR 3.7; 95% CI 1.5-9.4), functional class
      exceeding 2 (P = 0.004; OR 2.2; 95% CI 1.3-3.7), chromosomal abnormalities (P =
      0.004; OR 3.3; 95% CI 1.4-7.7), impaired renal function (P = 0.019; OR 3.8; 95%
      CI 1.2-11.5), systemic right ventricle (RV) in a biventricular circulation (P =
      0.027; OR 3.3; 95% CI 1.1-9.5), enlargement of the systemic ventricle (P = 0.011;
      OR 1.7; 95% CI 1.1-2.6), and operation with extracorporeal circulation (P =
      0.002; OR 4.3; 95% CI 1.7-11.4). Early mortality in the current adult CHD
      population is low. Morbidity, however, is significant and influenced by the
      patients' conditions (male gender, chromosomal abnormalities), history (cyanosis,
      New York Hospital Association [NYHA] class), and underlying morphology (systemic
      RV). This information for a large cohort of patients could help progress toward
      more adequate counseling for adults with a congenital heart defect.

PMID- 21901644
TI  - Assessment of coronary flow reserve in the coronary sinus by cine 3T-magnetic
      resonance imaging in young adults after surgery for tetralogy of Fallot.
AB  - This study aimed to evaluate CFR by assessing blood flow in the coronary sinus
      and systemic endothelial function measured by FMD of the brachial artery in an
      open prospective study of 10 control subjects and 10 patients (ages, 15-25 years)
      who have undergone surgical TOF repair. Reduced ventricular function, impaired
      exercise capacity, and ventricular arrhythmia have been proposed as risk factors
      for sudden cardiac death after surgical repair of TOF. Some of this may be
      related to impaired myocardial perfusion. A 3.0T GE Signa Excite scanner was used
      to achieve phase-contrast, velocity-encoding cine magnetic resonance imaging in
      the coronary sinus before and during infusion with adenosine (0.14 mg/kg/min).
      FMD was measured in the brachial artery before arterial occlusion and 5 min
      afterward. The TOF group demonstrated significantly higher volumetric blood flow
      in the coronary sinus (282 +/- 63 ml/min) than the normal control subjects at
      rest (184 +/- 57 ml/min) (P = 0.006). During adenosine infusion, this difference
      disappeared. The CFR was 2.00 +/- 0.43 in the control group and 1.19 +/- 0.34 in
      the TOF group (P = 0.002). No correlation between FMD and CFR was observed in the
      study group (r (s) = 0.61, n = 8, P = 0.15). This study showed a reduced CFR due
      to a higher blood flow of the subject at rest in the TOF group. This reduced CFR
      may disable a normal adaptation to increased oxygen demand during exercise and
      increase myocardial vulnerability to reduced blood supply postoperatively for TOF
      patients with coronary heart disease.

PMID- 21901645
TI  - Sexual dimorphism and personality attributions of male faces.
AB  - Individuals tend to judge personality traits on the basis of physical
      characteristics, particularly facial traits, although this phenomenon has been
      mostly studied in relation to the halo effect of attractiveness. However, there
      are other facial traits which may also have an impact on personality
      attributions; here, we focused on masculinity. We carried out principal component
      analysis (PCA) of 15 anthropometric measurements from 71 male faces, resulting in
      three components: Face Height (C1), Inner Face Breadth (C2), and Cheekbones-Jaw
      Prominence (C3). The targets' photographs were rated by 210 women and 177 men on
      scales for masculinity, attractiveness, and nine psychological characteristics
      (selected Cattell's factors): Warmth, Reasoning, Emotional Stability, Dominance,
      Liveliness, Rule-Consciousness, Social Boldness, Abstractedness, and Privateness.
      We found that masculinity correlated positively with ratings of Dominance and
      Social Boldness and that masculinity rated by men correlated positively with
      ratings of Emotional Stability and Privateness. We found no relationship between
      masculinity rated by women and the PCA components, while masculinity rated by men
      correlated negatively with C2 (possibly related to babyface features) and
      positively with C3 (which included features developed under the control of
      testosterone, such as jaw prominence). Our results imply sex differences in
      masculinity ratings. In particular, men used Cheekbones-Jaw Prominence and Inner
      Face Breadth as cues for masculinity judgments; on the other hand, women
      apparently perceive masculinity in a more holistic way.

PMID- 21901646
TI  - Effects of partner beauty on opposite-sex attractiveness judgments.
AB  - Many studies show mate choice copying effects on mate preferences in non-human
      species in which individuals follow or copy the mate choices of same-sex
      conspecifics. Recent studies suggest that social learning also influences mate
      preferences in humans. Studies on heterosexual humans have focused on rating the
      attractiveness of potential mates (targets) presented alongside individuals of
      the opposite sex to the target (models). Here, we examined several different
      types of pairing to examine how specific social learning is to mate preferences.
      In Study 1, we replicated a previous effect whereby target faces of the opposite
      sex to the subject were rated as more attractive when paired with attractive than
      unattractive partner models of the same sex as the subject. Using the same paired
      stimuli, Study 2 demonstrated no effect of a paired model if subjects were asked
      to rate targets who were the same sex as themselves. In Study 3, we used pairs of
      the same sex, stating the pair were friends, and subjects rated targets of the
      opposite sex to themselves. Attractive models decreased targets' attractiveness,
      opposite to the effect in Study 1. Finally, Study 4 examined if attractive versus
      unattractive non-face stimuli might influence attraction. Unlike in Study 1,
      pairing with attractive stimuli either had no effect or decreased the
      attractiveness of paired target face images. These data suggest that social
      transmission of preferences via pairing with attractive/unattractive images is
      relatively specific to learning about mate preferences but does not influence
      attractiveness judgments more generally.

PMID- 21901648
TI  - [Traumatic tricuspid valve insufficiency with right-to-left shunt: bridging using
      extracorporeal venovenous membrane oxygenation].
AB  - The case of a young male motor vehicle driver is reported who suffered multiple
      trauma in a car accident with pulmonary and cardiac contusions. In the course of
      severe pneumonia and traumatic tricuspid valve insufficiency a right-to-left
      shunt with refractory hypoxemia developed across a pre-existing atrial septal
      defect (ASD). The patient could be successfully treated by the combination of
      extracorporeal membrane oxygenation for bridging, interventional ASD occlusion
      and in the long-term by operative reconstruction of the tricuspid valve.

PMID- 21901649
TI  - Challenges and opportunities in implementing the FDA default parametric tolerance
      interval two one-sided test for delivered dose uniformity of orally inhaled
      products.
AB  - The goal of this article is to discuss considerations regarding implementation of
      the parametric tolerance interval two one-sided test (PTI-TOST) for delivered
      dose uniformity (DDU) of orally inhaled products (OIPs). That test was proposed
      by FDA in 2005 as an alternative to the counting test described in the 1998 draft
      FDA guidance for metered dose inhalers and dry powder inhalers. The 2005 PTI
      TOST, however, still has not found much use in practice despite the general
      desirability of parametric approaches in modern pharmaceutical quality control. A
      key reason for its slow uptake is that it rejects, with high probability, batches
      whose quality is considered acceptable by all other published regulatory and
      pharmacopeial standards as well as by the DDU specifications for many approved
      OIPs. Manufacturers therefore continue using nonparametric counting tests for
      control of DDU. A simulated case study presented here compares the consequences
      of the PTI-TOST compared to the counting test. The article discusses three
      possibilities that would help increase the uptake of the PTI-TOST approach,
      namely: product-specific quality standards, a different default standard suitable
      for the majority of OIPs, and integration of the PTI-TOST with a continuous
      verification control strategy rather than using it as an isolated-batch
      (transactional) end-product testing. In any of these efforts, if a parametric
      test is used, it is critical not to set the target quality close to, or at the
      boundary of the process/product capabilities, because PTI tests are designed to
      reject with high probability the identified target quality.

PMID- 21901651
TI  - Ongoing problems with authorship.

PMID- 21901650
TI  - Prevention--a cost-effective way to fight the non-communicable disease epidemic:
      an academic perspective of the United Nations High-level NCD Meeting.
AB  - The United Nations General Assembly has convened a Summit on non-communicable
      diseases (NCDs), an historic moment in the global combat of these disorders.
      Lifestyles in increasingly urban and globalised environments have led to a steep
      surge in NCD incidence in low and middle income countries, where two thirds of
      all NCD deaths occur (most importantly from cancer, cardiovascular and
      respiratory disease as well as diabetes). Treatment of NCDs is usually long term
      and expensive, thus threatening patients' and nations' budgets and putting them
      at high risk for poverty. The NCD Summit offers an opportunity for strengthening
      and shaping primary prevention, the most cost-effective instrument to fight major
      risk factors such as tobacco smoking, alcohol abuse, physical inactivity and
      unhealthy diet. From a Swiss perspective, we also emphasised the efforts for new
      laws on prevention and diagnosis registration, in accordance with the
      recommendations of the NCD summit in order to strengthen primary prevention and
      disease monitoring. In addition, the need for structural prevention across all
      policy sectors with leadership in environmental policy making to prevent NCDs as
      well as the need to adapt and strengthen primary health care are equally relevant
      for Switzerland. To compliment efforts in primary prevention, the field of NCDs
      requires special R&D platforms for affordable NCD drugs and diagnostics for
      neglected population segments in both Switzerland and low and middle income
      countries. Switzerland has a track record in research and development against
      diseases of poverty on a global scale that now needs to be applied to NCDs.

PMID- 21901652
TI  - Metal storage disorders. Forward.

PMID- 21901653
TI  - Clinical molecular diagnosis of Wilson disease.
AB  - Wilson disease is an autosomal recessive disorder of copper transport
      characterized by toxic accumulation of copper in the liver, brain, and other
      organs. It is lethal if untreated, but effective treatment is available. The
      broad spectrum of clinical manifestations, including hepatic and neuropsychiatric
      symptoms, can present over a large age range, contributing to difficulty in
      recognition of this disease. The diagnosis has traditionally rested on
      measurements of ceruloplasmin and copper in urine and liver, but it remains a
      challenge due to ambiguous biochemical results that can overlap with healthy
      carriers. Although hepatic copper concentration has been the gold standard for
      diagnosis, direct sequencing of the ATP7B gene is sensitive, specific, and can
      obviate the need for invasive liver biopsy. In this article, the authors review
      the sensitivity, limitations, and pitfalls of ATP7B sequencing in the diagnosis
      of Wilson disease. ATP7B sequencing should be standard practice in the diagnosis
      of Wilson disease.

PMID- 21901654
TI  - Pathology of the liver in copper overload.
AB  - Copper accumulation in the liver is associated with cellular and apoptotic
      injury. Wilson disease is the most well-characterized disorder of disordered
      copper metabolism. Other less-common disorders include Indian childhood
      cirrhosis, endemic Tyrolean infantile cirrhosis, and idiopathic copper toxicosis.
      The histopathologic spectrum of the liver in Wilson disease is extremely variable
      and overlaps among the different entities, though this review will focus on the
      pathology of Wilson disease. The findings lack specificity, although
      characteristic findings are observed. Unlike other disorders of copper overload,
      the pathologic changes are typically sequential, ranging from little or no
      significant findings to cirrhosis with or without widespread hepatocellular
      damage. Steatosis and glycogenated nuclei are frequent. Staining of copper is an
      unreliable method of diagnosis of Wilson disease, whether there are minimal
      histologic abnormalities or chronic liver disease. Copper and copper-associated
      protein accumulation may also be seen in chronic biliary obstructive processes.

PMID- 21901655
TI  - Wilson disease: pathogenesis and clinical considerations in diagnosis and
      treatment.
AB  - Nearly a century after Dr. Samuel Alexander Kinnier Wilson composed his doctoral
      thesis on the pathologic findings of "lenticular degeneration" in the brain
      associated with cirrhosis of the liver we know that the underlying molecular
      basis for this autosomal recessive inherited disorder that now bears his name is
      mutation of a copper transporting ATPase, ATP7B, an intracellular copper
      transporter mainly expressed in hepatocytes. Loss of ATP7B function is the basis
      for reduced hepatic biliary copper excretion and reduced incorporation of copper
      into ceruloplasmin. During the intervening years, there was recognition of the
      clinical signs, histologic, biochemical features, and mutation analysis of ATP7B
      that characterize and enable diagnosis of this disorder. These include the
      presence of signs of liver or neurologic disease and detection of Kayser
      Fleischer rings, low ceruloplasmin, elevated urine and hepatic copper, and
      associated histologic changes in the liver. Medical therapies and liver
      transplantation can effectively treat patients with this once uniformly fatal
      disorder. The earlier detection of the disease led to the initiation of treatment
      to prevent disease progression and reverse pathologic findings if present, and
      family screening to detect the disorder in first-degree relatives is warranted.
      Gene therapy and hepatocyte cell transplantation for Wilson disease has only been
      tested in animal models but represent future areas for study. Despite all the
      advances we still have to consider the diagnosis of Wilson disease to test
      patients for this disorder and properly establish the diagnosis before committing
      to life-long treatment.

PMID- 21901656
TI  - Pathology of hepatic iron overload.
AB  - The growing availability of genetic tests for most inherited iron-overload
      conditions and our current ability to assess hepatic iron stores, and at a lesser
      extent, liver fibrosis by noninvasive methods have reduced the need for liver
      biopsy in patients with hepatic iron excess. Histologic evaluation of the liver
      remains useful (1) in well-defined genetic iron overload disorders to evaluate
      associated hepatic damage, (2) in unclassified genetic or acquired iron excess to
      guide etiologic diagnosis and to establish prognosis, and (3) in research studies
      for a whole and reliable assessment of the liver. The identification of iron
      overload, the description of its cellular and lobular distribution,
      semiquantitative assessment of its amount, and inventory of associated lesions,
      especially fibrosis, are the pathologist's main objectives.

PMID- 21901658
TI  - The molecular pathogenesis of hereditary hemochromatosis.
AB  - Hereditary hemochromatosis is a genetic disorder of iron overload. Over the past
      15 years, significant advances have been made in understanding the molecular
      pathogenesis of this disorder. First, genetic studies linked this disorder to
      mutations in several genes, including HFE, transferrin receptor 2 ( TFR2),
      hepcidin ( HAMP), ferroportin ( SLC40A1), and hemojuvelin ( HFE2). Recent
      progress has generated significant insight into the function of these molecules
      in systemic iron homeostasis, and has revealed that despite the genetic and
      phenotypic diversity of hereditary hemochromatosis, there are common pathogenic
      mechanisms underlying this disease. The common downstream mechanism of iron
      overload in hereditary hemochromatosis is abnormal regulation of the hepcidin
      ferroportin axis, leading to a failure to prevent excess iron from entering the
      circulation. Recent data are starting to unravel the molecular mechanisms by
      which iron regulates hepcidin production, and has demonstrated a key role for the
      bone morphogenetic protein-hemojuvelin-SMAD signaling pathway in this process.
      Future studies will be needed to more fully understand the molecular mechanisms
      of iron sensing and the roles of HFE and TFR2 in this process. Here, the authors
      review the current state of knowledge on the molecular pathogenesis of hereditary
      hemochromatosis.

PMID- 21901659
TI  - Natural history and management of HFE-hemochromatosis.
AB  - Advances in our knowledge of hereditary hemochromatosis (HH) over the past 150
      years have revealed new insights into this common genetic disorder. Meticulous
      family and HLA association studies followed ultimately by cloning of the HFE gene
      have dramatically changed our understanding of the natural history and
      manifestations of HH. Cross-sectional studies demonstrated that HH had a highly
      variable clinical and biochemical penetrance in susceptible individuals of
      northern European descent. "State-of-the-art" large longitudinal population
      studies have accurately defined the natural history. We now recognize that HH is
      not as discreet an entity as previously thought because genetic and environmental
      modifiers of disease penetrance are increasingly identified as influencing the
      clinical course of HH. While phlebotomy remains the cornerstone of therapy, our
      diagnostic approach has been refined to incorporate new biochemical, genetic, and
      noninvasive methods that complement more traditional approaches. This review aims
      to encapsulate this new knowledge in a framework that addresses commonly raised
      issues relating to the current natural history, diagnosis, and management of HH
      patients.

PMID- 21901657
TI  - Hepcidin and ferroportin: the new players in iron metabolism.
AB  - Systemic iron homeostasis is regulated by the interaction of the peptide hormone,
      hepcidin and the iron exporter, ferroportin. Mutations in FPN1, the gene that
      encodes ferroportin, result in iron-overload disease that shows dominant
      inheritance and variation in phenotype. The inheritance of ferroportin-linked
      disorders can be explained by the finding that ferroportin is a multimer and the
      product of the mutant allele participates in multimer formation. The nature of
      the ferroportin mutant can explain the variation in phenotype, which is due to
      either decreased iron export activity or decreased ability to be downregulated by
      hepcidin. Iron export through ferroportin is determined by the concentration of
      ferroportin in plasma membrane, which is the result of both synthetic and
      degradation events. Ferroportin degradation can occur by hepcidin-dependent and
      hepcidin-independent internalization. Ferroportin expression is regulated
      transcriptionally and posttranslationally.

PMID- 21901660
TI  - Non-HFE hepatic iron overload.
AB  - Numerous clinical entities have now been identified to cause pathologic iron
      accumulation in the liver. Some are well described and have a verified hereditary
      basis; in others the genetic basis is still speculative, while in several cases
      nongenetic iron-loading factors are apparent. The non- HFE hemochromatosis
      syndromes identifies a subgroup of hereditary iron loading disorders that share
      with classic HFE-hemochromatosis, the autosomal recessive trait, the pathogenic
      basis (i.e., lack of hepcidin synthesis or activity), and key clinical features.
      Yet, they are caused by pathogenic mutations in other genes, such as transferrin
      receptor 2 ( TFR2), hepcidin ( HAMP), hemojuvelin ( HJV) , and ferroportin (
      FPN), and, unlike HFE-hemochromatosis, are not restricted to Caucasians.
      Ferroportin disease, the most common non- HFE hereditary iron-loading disorder,
      is caused by a loss of iron export function of FPN resulting in early and
      preferential iron accumulation in Kupffer cells and macrophages with high
      ferritin levels and low-to-normal transferrin saturation. This autosomal dominant
      disorder has milder expressivity than hemochromatosis. Other much rarer genetic
      disorders are associated with hepatic iron load, but the clinical picture is
      usually dominated by symptoms and signs due to failure of other organs (e.g.,
      anemia in atransferrinemia or neurologic defects in aceruloplasminemia). Finally,
      in the context of various necro-inflammatory or disease processes (i.e., chronic
      viral or metabolic liver diseases), regional or local iron accumulation may occur
      that aggravates the clinical course of the underlying disease or limits efficacy
      of therapy.

PMID- 21901661
TI  - Atypical presentation of Wilson disease.
AB  - A 15-year-old Caucasian female on human chorionic gonadotropin (HCG) diet
      presented with fever, cholestasis, coagulopathy, hemolytic anemia, and acute
      renal dysfunction. Imaging of the biliary system and liver were normal. She
      responded to intravenous antibiotics, vitamin K and blood transfusions but
      experienced relapse upon discontinuation of antibiotics. She had remission with
      reinstitution of antibiotics. Liver biopsy revealed pronounced bile ductular
      reaction, bridging fibrosis, and hepatocytic anisocytosis and anisonucleosis with
      degenerative enlarged eosinophilic hepatocytes, suggestive of Wilson disease.
      Diagnosis of Wilson disease was further established based on the low serum
      ceruloplasmin, increased urinary and hepatic copper and presence of Kayser
      Fleischer rings. The multisystem involvement of the liver, kidney, blood, and
      brain are consistent with Wilson disease; however, the clinical presentation of
      cholangitis and reversible coagulopathy is uncommon, and may result from
      concurrent acute cholangitis and/or the HCG diet regimen the patient was on.

PMID- 21901662
TI  - [Papilledema and echographically detectable retro-orbital dilatation of the sub
      arachnoidal space with open fontanelle - six case reports].
AB  - This paper analyses the case reports for three children in which a papilledema
      occurred before the age of one year. Furthermore, an analysis is also given of
      three further case reports for children aged less than one year in which, in
      spite of open fontanelle, no papilledema was found, however, a dilatation of the
      sub-arachnoidal space was demonstrated echographically. Even in children less
      than one year of age in which an open fontanelle still exists and in whom a neuro
      paediatric clarification of internal hydrocepalus is made, in spite of
      opththalmoscopically inconspicuous findings for the papilla an echography is
      indispensable for the evaluation of the sub-arachnoidal space. Here, the early
      recognition of a dilatation of the retro-bulbar sub-arachnoidal space can
      possibly prevent the occurrence of a consecutive optic atrophy. At the present
      time, the data available do not allow the recommendation of an upper age limit
      for an echographic examination.

PMID- 21901663
TI  - [Quantitative analysis of corneal subbasal nerve plexus with in vivo confocal
      laser scanning microscopy].
AB  - BACKGROUND: An analysis of the corneal subbasal nerve plexus (SNP) allows an
      evaluation of the peripheral neuropathy in cases of degenerative diseases. In
      order to study the SNP structures quantitatively the automatically calculated
      morphological and topological parameters are required. METHODS: In vivo confocal
      laser scanning microscopy (Heidelberg Retina Tomograph II/Rostock Cornea Module)
      was performed in healthy volunteers as well as patients with severe diabetic
      neuropathy. An adapted image processing algorithm was used to preprocess, segment
      and evaluate quantitatively the nerve fibers of the SNP. Data sets were analysed
      statistically. RESULTS: The developed algorithm allows an automated detection of
      SNP structures. Furthermore, it allows the collection of data based on
      morphological and topological parameters. The main parameters that show
      significant differences between healthy cornea and cases of diabetic neuropathy
      are nerve fibre density and length, number of branching, tortuosity and number of
      terminal and crossing points. All parameters of the measurements can be used
      isolated, combined or weighted for quantification of the SNP networks.
      CONCLUSION: The presented fully automated preprocessing eliminates a large number
      of motion-induced artefacts. The quality of the resulting pictures allows an
      automated quantification using characteristic measurements. This represents an in
      vivo, non-invasive technology analysing degenerative changes of SNP especially in
      the course of diabetes mellitus.

PMID- 21901664
TI  - [The history of oxygen--from its discovery to its implementation as medical
      therapy].

PMID- 21901665
TI  - Gastric duplication cysts of the pancreas: clinical presentation and surgical
      management.

PMID- 21901666
TI  - [Objective assessment of total noise exposure over 24 hours: a cross-sectional
      study in Bavaria].
AB  - INTRODUCTION: Noise can affect well-being and performance of individuals and
      might be associated with an increased risk of cardiovascular events. To date most
      epidemiological studies considered exposure from a single source of noise. The EU
      Environmental Noise Directive (2002/49/EC) requires a summative measurement of
      ambient noise. This study aimed to capture the participants' exposure to
      environmental noise by means of personal noise dosimetry. METHODS: Children
      (n=628, participation=61%, age 8-12 years), adolescents (n=632,
      participation=58%, age 13-17 years) and adults (n=482, participation=40%, age 18
      65 years) were selected randomly from the population registry of 4 Bavarian towns
      and were invited to participate in a 24-h measurement using noise dosimetry.
      Noise exposures during day and night were analyzed separately. In addition,
      predictors of noise exposure were assessed. RESULTS: For daytime noise exposure
      mean+/-standard deviation were in children 80.0+/-5.8 dB(A), in adolescents
      76.0+/-6.2 dB(A), in adults 72.1+/-6.1 dB(A) (p(ANOVA)<0.001). During the day
      personal noise exposure was statistically significantly higher for participants
      from smaller towns than for those living in Munich, while nighttime noise
      exposure was highest for participants from Munich [44.1+/-7.2 dB(A)]. CONCLUSION:
      The summative noise exposure in urban Bavaria is high, in particular among
      children at daytime. Increased exposure levels in children might be caused by
      themselves while, e.g., playing. Whether the higher daytime exposure in towns is
      due to high noise levels commuting between home and work has to be assessed in
      future studies.

PMID- 21901667
TI  - [Type of school, social capital and subjective health in adolescence].
AB  - OBJECTIVES: Social capital is increasingly acknowledged as a central determinant
      of health. While several studies among adults have shown the importance of social
      capital for the explanation of social inequalities in health, few comparable
      studies exist which focus on adolescents. The study examines the role of social
      capital in different social contexts for the explanation of health inequalities
      in adolescence. METHODS: Data were obtained from the 'Health Behaviour in School
      aged Children (HBSC)' study in North Rhine-Westphalia from 2006. The sample
      includes data of 4323 11-15-year-old students. To analyse the role of social
      capital in the contexts family, school, friends and neighbourhood for
      inequalities in self-rated health and psychosomatic complaints, logistic
      regression models were calculated. The socioeconomic position of the adolescents
      was measured by type of school. RESULTS: Adolescents from general schools
      reported higher prevalences of fair/poor self-rated health and repeated
      psychosomatic complaints than pupils from grammar schools. Social capital in all
      4 contexts (family, school, friends, and neighbourhood) was associated with both
      health indicators, independent of gender. In the separate analysis the variables
      for social capital showed a comparable explanatory contribution and reduced the
      odds ratios of self-rated health by 6-9%. The contribution for psychosomatic
      complaints was slightly higher with 10-15%. The only exception was social capital
      among friends which showed no effect for both health indicators. In the joint
      analysis the variables for social capital explained about 15% to 30% of health
      inequalities by school type. CONCLUSIONS: The results show that, already in
      adolescence, inequalities in subjective health can be partly explained through
      socioeconomic differences in the availability of social capital. The settings
      family, neighbourhood and school provide ideal contexts for preventive actions
      and give the opportunity to directly address the high-risk group of students from
      general schools.

PMID- 21901668
TI  - [(Inter)national and regional health goals in academic social-medical education
      conception for teaching medical students at the Eberhard Karls University
      Tuebingen].
AB  - BACKGROUND: Social medicine deals with the specific interactions between medicine
      and society within a constantly changing social environment. The Institute of
      Occupational and Social Medicine, University Hospital Tuebingen, focuses on this
      relationship within the academic teaching of the Medical Faculty. Many of the
      issues thus directly affect the national health objectives and especially the
      health targets of the state of Baden-Wurttemberg, summarised in the Health
      Strategy Baden-Wuerttemberg. MATERIAL AND METHODS: In addition to the
      recommendations of the German Society for Social Medicine and Prevention (DGSMP)
      for the social medicine curriculum and the specific definition of the content by
      the Tuebingen medical faculty, national and regional health-care goals are also
      taken into account in the teaching conception. RESULTS: Classes are increasingly
      offered as training courses in small groups (seminars, group work with practical
      training), instead of classic lectures. These teaching methods allow the students
      to take part more actively in social medicine issues and to think and act within
      a comprehensive understanding of health management based on societal goals and
      the needs of a good health system. The concept is supported by the curriculum
      design element "log-book skills" of the Medical Faculty of Tuebingen. Feedback
      elements for teachers and students shape the further development of the concept.
      In dealing with real system data, practical experience on site and case
      vignettes, the students experience the links between societal influences,
      political objectives and medical action as well as the importance of
      accessibility of medical services for equity in health chances. CONCLUSIONS: The
      fact that advice and expertise play a crucial role in accessibility is a
      component to which too little attention is paid and calls for emphasis in the
      teaching concept. This teaching approach will deepen the understanding of the
      influence of psychosocial context factors and the conditions of the structural
      framework on the medical outcome. Furthermore there is a need for providing
      knowledge and special skills, which enable medical doctors to guide their
      patients optimally within the healthcare system and to make their contribution to
      a good system.

PMID- 21901669
TI  - Common buffers and stock solutions.

PMID- 21901670
TI  - A status update of modified oligonucleotides for chemotherapeutics applications.
AB  - This unit presents an update of recent developments and clinical progress in
      chemically modified oliogonucleotides useful for therapeutic applications. During
      the last decade, the number of therapeutic oligonucleotides in clinical trials
      has nearly tripled. This is primarily due to advances in the synthesis protocols,
      better understanding of the biology, improved delivery, and better formulation
      technologies. Currently, over 100 clinical trials with oligonucleotide-based
      drugs are ongoing in the United States for potential treatment of a variety of
      life-threatening diseases. Among various oligonucleotides, antisense technology
      has been at the forefront, with one product on the market. Antisense technologies
      represent about half of the active clinical trials. Similarly, siRNA, aptamers,
      spiegelmers microRNA, shRNA, IMO, and CpG have been other active classes of
      oligonucleotides that are also undergoing clinical trials. This review attempts
      to summarize the current status of synthesis, chemical modifications,
      purification, and analysis in light of the rapid progress with multitude of
      oligonucleotides pursued as therapeutic modality.

PMID- 21901671
TI  - Preparation of photoresponsive DNA tethering ortho-methylated azobenzene as a
      supra-photoswitch.
AB  - This unit describes synthetic procedures of photoresponsive DNA via a
      phosphoramidite monomer composed of D-threoninol as a scaffold and 4-carboxy
      2',6'-dimethylazobenzene or 4-carboxy-2'-methylazobenzene that works as a
      photoswitch more efficiently than previous nonmodified azobenzene (4
      phenylazobenzoic acid). With these newly modified-azobenzenes, photoregulatory
      efficiency of DNA hybridization can be greatly improved. Furthermore, thermal
      stability of cis-azobenzene of 4-carboxy-2',6'-dimethylazobenzene remarkably
      increases compared with the previous non-modified azobenzene.

PMID- 21901672
TI  - RNA aptamers and spiegelmers: synthesis, purification, and post-synthetic PEG
      conjugation.
AB  - This unit describes the solid-phase synthesis and downstream processing for RNA
      oligonucleotides with a length of up to 40 to 50 nucleotides on a 1- to 4-mmol
      scale with subsequent conjugation to PEG using the L-RNA spiegelmer NOX-E36 as an
      example. Following synthesis and two-step deprotection, the crude oligonucleotide
      is purified by preparative reversed-phase HPLC and desalted by tangential flow
      ultrafiltration. The resulting intermediate amino-modified oligonucleotide is
      reacted with NHS-ester-activated PEG, and the oligonucleotide-PEG conjugate is
      obtained after preparative AX-HPLC purification, followed by ultrafiltration and
      lyophilization. Critical process parameters are described, as well as time
      considerations and examples for analytical methods used as in-process and quality
      controls.

PMID- 21901673
TI  - Use of chromophoric ligands to visually screen co-crystals of putative protein
      nucleic acid complexes.
AB  - Distinguishing between crystals of protein-nucleic acid complexes and those
      containing protein alone is a common problem in structural studies of protein
      nucleic acid interactions. Currently, there are several methods available for
      detecting nucleic acid in crystals, including gel electrophoresis, SYBR Gold
      fluorescence dye staining, and methyl violet staining. However, they require
      either that the crystals be sacrificed or access to a fluorescence microscope. In
      this protocol, we describe an approach that allows direct visualization of either
      the presence or absence of oligonucleotides in crystals grown from solutions
      containing both protein and nucleic acid--labeling with the Cy5 dye. In addition
      to offering the advantage of being able to distinguish between crystals of
      complex and protein alone with the naked eye or a light microscope, crystals of
      covalently Cy5-labeled DNA can be directly used for X-ray diffraction data
      collection.

PMID- 21901674
TI  - Corticosteroids for acute ischaemic stroke.
AB  - BACKGROUND: The majority of strokes are due to cerebral infarction. Ischaemic
      cerebral tissue tends to develop cytotoxic oedema which, if the blood-brain
      barrier is disrupted, may be followed by vasogenic oedema. Large infarcts can
      develop life-threatening massive oedema. Early treatment with corticosteroids
      could theoretically help reduce both cytotoxic and vasogenic oedema and so
      improve the clinical outcome after a stroke. OBJECTIVES: To assess the effect of
      corticosteroids in acute presumed ischaemic stroke. SEARCH STRATEGY: We searched
      the Cochrane Stroke Group Trials Register (last searched: 17 February 2011).
      SELECTION CRITERIA: Published randomised trials comparing corticosteroids with
      placebo or a control group in people with acute (presumed or definite) ischaemic
      stroke. Trials were included if treatment began within 48 hours of stroke onset
      and if clinical outcomes were assessed. DATA COLLECTION AND ANALYSIS: Two review
      authors independently applied the inclusion criteria, assessed trial quality and
      extracted the data. MAIN RESULTS: Eight trials involving 466 people were
      included. Details of trial quality that may relate to bias were not available for
      most trials. No difference was shown in the odds of death within one year (odds
      ratio (OR) 0.87, 95% confidence interval (CI) 0.57 to 1.34). Treatment did not
      appear to improve functional outcome in survivors. Seven trials reported
      neurological impairment but pooling the data was impossible because no common
      scale or time interval was used. The results were inconsistent between individual
      trials. The only adverse effects reported were small numbers of gastrointestinal
      bleeds, infections and deterioration of hyperglycaemia across both groups. The
      results are unchanged since the previous update. AUTHORS' CONCLUSIONS: There is
      not enough evidence to evaluate corticosteroid treatment for people with acute
      presumed ischaemic stroke. The conclusions are unchanged since the previous
      update.

PMID- 21901675
TI  - Counselling for mental health and psychosocial problems in primary care.
AB  - BACKGROUND: The prevalence of mental health and psychosocial problems in primary
      care is high. Counselling is a potential treatment for these patients, but there
      is a lack of consensus over the effectiveness of this treatment in primary care.
      OBJECTIVES: To assess the effectiveness and cost effectiveness of counselling for
      patients with mental health and psychosocial problems in primary care. SEARCH
      STRATEGY: To update the review, the following electronic databases were searched:
      the Cochrane Collaboration Depression, Anxiety and Neurosis (CCDAN) trials
      registers (to December 2010), MEDLINE, EMBASE, PsycINFO and the Cochrane Central
      Register of Controlled Trials (to May 2011). SELECTION CRITERIA: Randomised
      controlled trials of counselling for mental health and psychosocial problems in
      primary care. DATA COLLECTION AND ANALYSIS: Data were extracted using a
      standardised data extraction sheet by two reviewers. Trials were rated for
      quality by two reviewers using Cochrane risk of bias criteria, to assess the
      extent to which their design and conduct were likely to have prevented systematic
      error. Continuous measures of outcome were combined using standardised mean
      differences. An overall effect size was calculated for each outcome with 95%
      confidence intervals (CI). Continuous data from different measuring instruments
      were transformed into a standard effect size by dividing mean values by standard
      deviations. Sensitivity analyses were undertaken to test the robustness of the
      results. Economic analyses were summarised in narrative form. There was no
      assessment of adverse events. MAIN RESULTS: Nine trials were included in the
      review, involving 1384 randomised participants. Studies varied in risk of bias,
      although two studies were identified as being at high risk of selection bias
      because of problems with concealment of allocation. All studies were from primary
      care in the United Kingdom and thus comparability was high. The analysis found
      significantly greater clinical effectiveness in the counselling group compared
      with usual care in terms of mental health outcomes in the short-term
      (standardised mean difference -0.28, 95% CI -0.43 to -0.13, n = 772, 6 trials)
      but not in the long-term (standardised mean difference -0.09, 95% CI -0.27 to
      0.10, n = 475, 4 trials), nor on measures of social function (standardised mean
      difference -0.09, 95% CI -0.29 to 0.11, n = 386, 3 trials). Levels of
      satisfaction with counselling were high. There was some evidence that the overall
      costs of counselling and usual care were similar. There were limited comparisons
      between counselling and other psychological therapies, medication, or other
      psychosocial interventions. AUTHORS' CONCLUSIONS: Counselling is associated with
      significantly greater clinical effectiveness in short-term mental health outcomes
      compared to usual care, but provides no additional advantages in the long-term.
      Participants were satisfied with counselling. Although some types of health care
      utilisation may be reduced, counselling does not seem to reduce overall
      healthcare costs. The generalisability of these findings to settings outside the
      United Kingdom is unclear.

PMID- 21901676
TI  - Intravenous or enteral loop diuretics for preterm infants with (or developing)
      chronic lung disease.
AB  - BACKGROUND: Lung disease in preterm infants is often complicated with lung edema.
      OBJECTIVES: To assess the risks and benefits of administration of a diuretic
      acting on the loop of Henle (loop diuretic) in preterm infants with or developing
      chronic lung disease (CLD). SEARCH STRATEGY: Standard search method of the
      Cochrane Neonatal Review Group was used. Initial search included the Cochrane
      Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1,
      2003), MEDLINE (1966 to April 2003), EMBASE (1974 to 1998). In addition, several
      abstract books of national and international American and European Societies were
      hand searched. The MEDLINE and the Cochrane Central searches were updated in
      March 2007 and December 2010.  The EMBASE search was completed in April 2007 and
      December 2010. Additional searches in CINAHL, clinicaltrials.gov and controlled
      trials.com was completed in December 2010. SELECTION CRITERIA: Trials in which
      preterm infants with or developing chronic lung disease and at least five days of
      age were all randomly allocated to receive a loop diuretic either enterally or
      intravenously were included in this analysis. DATA COLLECTION AND ANALYSIS: The
      standard method for the Cochrane Collaboration described in the Cochrane
      Collaboration Handbook were used. Two investigators extracted, assessed and coded
      separately all data for each study. Parallel and cross-over trials were combined
      and, whenever possible, transformed baseline and final outcome data measured on a
      continuous scale into change scores using Follmann's formula. MAIN RESULTS: The
      only loop diuretic used in the six studies that met the selection criteria was
      furosemide. Most studies focused on pathophysiological parameters and did not
      assess effects on important clinical outcomes defined in this review, or the
      potential complications of diuretic therapy. In preterm infants < 3 weeks of age
      developing CLD, furosemide administration has either inconsistent effects or no
      detectable effect. In infants > 3 weeks of age with CLD, a single intravenous
      dose of 1 mg/kg of furosemide improves lung compliance and airway resistance for
      one hour. Chronic administration of furosemide improves both oxygenation and lung
      compliance. AUTHORS' CONCLUSIONS: In view of the lack of data from randomized
      trials concerning effects on important clinical outcomes, routine or sustained
      use of systemic loop diuretics in infants with (or developing) CLD cannot be
      recommended based on current evidence. Randomized trials are needed to assess the
      effects of furosemide administration on survival, duration of ventilatory support
      and oxygen administration, length of hospital stay, potential complications and
      long-term outcome.

PMID- 21901677
TI  - Mechanical bowel preparation for elective colorectal surgery.
AB  - BACKGROUND: The presence of bowel contents during colorectal surgery has been
      related to anastomotic leakage, but the belief that mechanical bowel preparation
      (MBP) is an efficient agent against leakage and infectious complications is based
      on observational data and expert opinions only.An enema before the rectal surgery
      to clean the rectum and facilitate the manipulation for the mechanical
      anastomosis is used for many surgeons. This is analysed separately OBJECTIVES: To
      determine the security and effectiveness of MBP on morbidity and mortality in
      colorectal surgery. SEARCH STRATEGY: Publications describing trials of MBP before
      elective colorectal surgery were sought through searches of MEDLINE, EMBASE,
      LILACS, IBECS and The Cochrane Library; by handsearching relevant medical
      journals and conference proceedings, and through personal communication with
      colleagues.Searches were performed December 1, 2010. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) including participants submitted for elective
      colorectal surgery. Eligible interventions included any type of MBP compared with
      no MBP. Primary outcomes included anastomosis leakage - both rectal and colonic -
      and combined figures. Secondary outcomes included mortality, peritonitis,
      reoperation, wound infection, extra-abdominal complications, and overall surgical
      site infections. DATA COLLECTION AND ANALYSIS: Data were independently extracted
      and checked. The methodological quality of each trial was assessed. Details of
      randomisation, blinding, type of analysis, and number lost to follow up were
      recorded. For analysis, the Peto-Odds Ratio (OR) was used as the default (no
      statistical heterogeneity was observed). MAIN RESULTS: At this update six trials
      and a new comparison (Mechanical bowel preparation versus enema) were added.
      Altogether eighteen trials were analysed, with 5805 participants; 2906 allocated
      to MBP (Group A), and 2899 to no preparation (Group B), before elective
      colorectal surgery.For the comparison Mechanical Bowel Preparation Versus No
      Mechanical Bowel Preparation results were:1. Anastomotic leakage for low anterior
      resection: 8.8% (38/431) of Group A, compared with 10.3% (43/415) of Group B;
      Peto OR 0.88 [0.55, 1.40].2. Anastomotic leakage for colonic surgery: 3.0%
      (47/1559) of Group A, compared with 3.5% (56/1588) of Group B; Peto OR 0.85
      [0.58, 1.26].3. Overall anastomotic leakage: 4.4% (101/2275) of Group A, compared
      with 4.5% (103/2258) of Group B; Peto OR 0.99 [0.74, 1.31].4. Wound infection:
      9.6% (223/2305) of Group A, compared with 8.5% (196/2290) of Group B; Peto OR
      1.16 [0.95, 1.42].Sensitivity analyses did not produce any differences in overall
      results.For the comparison Mechanical Bowel Preparation (A) Versus Rectal Enema
      (B) results were:1. Anastomotic leakage after rectal surgery: 7.4% (8/107) of
      Group A, compared with 7.9% (7/88) of Group B; Peto OR 0.93 [0.34, 2.52].2.
      Anastomotic leakage after colonic surgery: 4.0% (11/269) of Group A, compared
      with 2.0% (6/299) of Group B; Peto OR 2.15 [0.79, 5.84].3. Overall anastomotic
      leakage: 4.4% (27/601) of Group A, compared with 3.4% (21/609) of Group B; Peto
      OR 1.32 [0.74, 2.36].4. Wound infection: 9.9% (60/601) of Group A, compared with
      8.0% (49/609) of Group B; Peto OR 1.26 [0.85, 1.88]. AUTHORS' CONCLUSIONS:
      Despite the inclusion of more studies with a total of 5805 participants, there is
      no statistically significant evidence that patients benefit from mechanical bowel
      preparation, nor the use of rectal enemas. In colonic surgery the bowel cleansing
      can be safely omitted and induces no lower complication rate. The few studies
      focused in rectal surgery suggested that mechanical bowel preparation could be
      used selectively, even though no significant effect was found. Further research
      on patients submitted for elective rectal surgery, below the peritoneal verge, in
      whom bowel continuity is restored, and studies with patients submitted to
      laparoscopic surgeries are still warranted.

PMID- 21901678
TI  - Bromperidol decanoate (depot) for schizophrenia.
AB  - BACKGROUND: Antipsychotic drugs are the mainstay treatment for schizophrenia.
      Long-acting depot injections of drugs such as bromperidol decanoate are
      extensively used as a means of long-term maintenance treatment. OBJECTIVES: To
      assess the effects of depot bromperidol versus placebo, oral antipsychotics and
      other depot antipsychotic preparations for people with schizophrenia in terms of
      clinical, social and economic outcomes. SEARCH STRATEGY: For this 2011 update we
      searched the Cochrane Schizophrenia Group's Register (February 2011). SELECTION
      CRITERIA: We sought all randomised trials focusing on people with schizophrenia
      where depot bromperidol, oral antipsychotics or other depot preparations. Primary
      outcomes were clinically significant change in global function, service
      utilisation outcomes (hospital admission, days in hospital), relapse. DATA
      COLLECTION AND ANALYSIS: For this 2011 update MP independently extracted data,
      CEA carried out the reliability check. We calculated fixed-effect risk ratios
      (RR) and 95% confidence intervals (CI) for dichotomous data, and calculated
      weighted or standardised means for continuous data. Where possible, we calculated
      the number needed to treat statistic (NNT). Analysis was by intention-to-treat.
      MAIN RESULTS: We have included no new trials in this 2011 update (4 RCTs, total n
      = 117). A single, small study of six months' duration compared bromperidol
      decanoate with placebo injection. Similar numbers left the study before
      completion (n = 20, 1 RCT, RR 0.4 CI 0.1 to 1.6) and there were no clear
      differences between bromperidol decanoate and placebo for a list of adverse
      effects (n = 20, 1 RCT, RR akathisia 2.0 CI 0.21 to 18.69, RR increased weight
      3.0 CI 0.14 to 65.9, RR tremor 0.33 CI 0.04 to 2.69). When bromperidol decanoate
      was compared with fluphenazine depot, we found no important change on global
      outcome (n = 30, RR no clinical important improvement 1.50 CI 0.29 to 7.73).
      People allocated to fluphenazine decanoate and haloperidol decanoate had fewer
      relapses than those given bromperidol decanoate (n = 77, RR 3.92 Cl 1.05 to
      14.60, NNH 6 CI 2 to 341). People allocated bromperidol decanoate required
      additional antipsychotic medication somewhat more frequently than those taking
      fluphenazine decanoate and haloperidol decanoate, but the results did not reach
      conventional levels of statistical significance (n = 77, 2 RCTs, RR 1.72 CI 0.7
      to 4.2). The use of benzodiazepine drugs was very similar in both groups (n = 77,
      2 RCTs, RR 1.08 CI 0.68 to 1.70). People left the bromperidol decanoate group
      more frequent than those taking other depot preparation due to any cause (n = 97,
      3 RCTs, RR 2.17 CI 1.00 to 4.73). Anticholinergic adverse effects were equally
      common between bromperidol and other depots (n = 47, RR 3.13 CI 0.7 to 14.0) and
      additional anticholinergic medication was needed with equal frequency in both
      depot groups, although results did tend to favour the bromperidol decanoate group
      (n = 97, 3 RCTs, RR 0.80 CI 0.64 to 1.01). The incidence of movement disorders
      was similar in both depot groups (n = 77, 2 RCTs, RR 0.74 CI 0.47 to 1.17).
      AUTHORS' CONCLUSIONS: Minimal poorly reported trial data suggests that
      bromperidol decanoate may be better than placebo injection but less valuable than
      fluphenazine or haloperidol decanoate. If bromperidol decanoate is available it
      may be a viable choice, especially when there are reasons not to use fluphenazine
      or haloperidol decanoate. Well-conducted and reported randomised trials are
      needed to inform practice.

PMID- 21901679
TI  - Diuretics acting on the distal renal tubule for preterm infants with (or
      developing) chronic lung disease.
AB  - BACKGROUND: Lung disease in preterm infants is often complicated with lung edema.
      OBJECTIVES: To assess the risks and benefits of diuretics acting on distal
      segments of the renal tubule (distal diuretics) in preterm infants with or
      developing chronic lung disease (CLD). SEARCH STRATEGY: The standard method of
      the Cochrane Neonatal Review Group were used. Initially, MEDLINE (1966 to
      November 2001), EMBASE (1974 to November 2001) and the Cochrane Controlled Trials
      Register (CENTRAL,The Cochrane Library, Issue 4, 2001) were searched. In
      addition, several abstract books of national and international American and
      European Societies were hand searched. Updated searches in April 2003, April
      2007, and December 2010 did not yield any additional trials. SELECTION CRITERIA:
      Included in this analysis are trials in which preterm infants with or developing
      CLD and at least five days of age were randomly allocated to receive a diuretic
      acting on the distal renal tubule. Eligible studies needed to assess at least one
      of the outcome variables defined a priori for this systematic review. DATA
      COLLECTION AND ANALYSIS: The standard method for the Cochrane Collaboration
      described in the Cochrane Collaboration Handbook were used. Two investigators
      extracted, assessed and coded separately all data for each study. Any
      disagreement was resolved by discussion. Parallel and cross-over trials were
      combined. Whenever possible, baseline and final outcome data measured on a
      continuous scale was transformed into change scores using Follmann's formula.
      MAIN RESULTS: Of the six studies fulfilling entry criteria, most focused on
      pathophysiological parameters and did not assess effects on important clinical
      outcomes defined in this review, or the potential complications of diuretic
      therapy.In preterm infants > 3 weeks of age with CLD, a four week treatment with
      thiazide and spironolactone improved lung compliance and reduced the need for
      furosemide. A single study showed thiazide and spironolactone decreased the risk
      of death and tended to decrease the risk for remaining intubated after eight
      weeks in infants who did not have access to corticosteroids, bronchodilators or
      aminophylline. AUTHORS' CONCLUSIONS: In preterm infants > 3 weeks of age with
      CLD, acute and chronic administration of distal diuretics improve pulmonary
      mechanics. However, positive effects should be interpreted with caution as the
      numbers of patients studied are small in surprisingly few randomized controlled
      trials.

PMID- 21901680
TI  - Dietary advice with or without oral nutritional supplements for disease-related
      malnutrition in adults.
AB  - BACKGROUND: Disease-related malnutrition has been reported in 10% to 55% of
      people in hospital and the community. Dietary advice encouraging the use of
      energy- and nutrient-rich foods rather than oral nutritional supplements has been
      suggested as the initial approach for managing disease-related malnutrition.
      OBJECTIVES: To examine evidence that dietary advice in adults with disease
      related malnutrition improves survival, weight and anthropometry; to estimate the
      size of any additional effect of nutritional supplements combined with dietary
      advice and to compare the effects of dietary advice with oral nutritional
      supplements. SEARCH STRATEGY: Relevant publications were identified from
      comprehensive electronic database searches and handsearching.Last search: 14
      February 2010. SELECTION CRITERIA: Randomised controlled trials of dietary advice
      with or without oral nutritional supplements in people with disease-related
      malnutrition in any health-care setting compared with no advice, oral nutritional
      supplements or dietary advice given alone. DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed trial eligibility, risk of bias and extracted
      data. MAIN RESULTS: Forty-five studies (3186 participants) met the inclusion
      criteria; (dietary advice compared with: no advice (1053 participants); with oral
      nutritional supplements (332 participants); with dietary advice and oral
      nutritional supplements (731 participants); and dietary advice plus oral
      nutritional supplements compared with no additional intervention (1070
      participants). Follow-up ranged from 18 days to 24 months. No comparison showed a
      significant difference between groups for mortality or morbidity. There was a
      significant change in weight found between groups when comparing dietary advice
      to no advice for interventions lasting greater than 12 months, mean difference
      3.75 kg (95% confidence interval 0.97 to 6.53), and when all studies were
      combined, mean difference 1.47 kg (95% confidence interval 0.32 to 2.61) although
      there was significant heterogeneity in the combined analysis (I(2) = 90%).
      Similar improvements in weight were found for the comparison of dietary advice
      with nutritional supplements if required versus no advice, mean difference 2.20
      kg (95% confidence interval 1.16 to 3.25). Dietary advice compared with no advice
      was also associated with significantly improved mid-arm muscle circumference when
      all studies were combined, but with moderate heterogeneity, mean difference 0.81
      mm (95% confidence interval 0.31 to 1.31). Dietary advice given with nutritional
      supplements compared with dietary advice alone resulted in improvements in: mid
      arm muscle circumference, mean difference -0.89 mm (95% confidence interval -1.35
      to -0.43); triceps skinfold thickness, mean difference -1.22 mm (95% confidence
      interval -2.34 to -0.09); and grip strength, mean difference -1.67 kg (95%
      confidence interval -2.96 to -0.37), although the effects on triceps skinfold
      thickness and grip strength were heterogeneous. Dietary advice with supplements
      if required resulted in a significant increase in triceps skinfold thickness
      compared with no advice, mean difference 0.40 mm (95% confidence interval 0.10 to
      0.70), although these results are from a single trial with only 29 participants.
      AUTHORS' CONCLUSIONS: Evidence of variable quality suggests that dietary advice
      with or without oral nutritional supplements may improve weight, body composition
      and grip strength. We found no evidence of benefit of dietary advice or oral
      nutritional supplements given alone or in combination on survival. Studies
      addressing the impact of nutritional interventions on nutritional, functional and
      patient-centred outcomes are needed.

PMID- 21901681
TI  - WITHDRAWN: Tamsulosin for benign prostatic hyperplasia.
AB  - BACKGROUND: Benign prostatic hyperplasia (BPH) is a nonmalignant enlargement of
      the prostate which can result in bothersome lower urinary tract symptoms. The
      treatment goal for men with BPH is to relieve these bothersome symptoms.
      OBJECTIVES: This systematic review assessed the effects of tamsulosin in the
      treatment of lower urinary tract symptoms (LUTS) compatible with BPH. SEARCH
      STRATEGY: Trials were searched in computerized general and specialized databases
      (MEDLINE, EMBASE, Cochrane Library), by checking bibliographies, and by
      contacting manufacturers and researchers. SELECTION CRITERIA: Trials were
      eligible if they (1) randomized men with BPH to receive tamsulosin in comparison
      with placebo, other BPH medications or surgical interventions and (2) included
      clinical outcomes such as urologic symptom scales, symptoms, or urodynamic
      measurements, and (3) had a treatment duration of 30 days or longer. Eligibility
      was assessed by at least two independent observers. DATA COLLECTION AND ANALYSIS:
      Information on patients, interventions, and outcomes were extracted by at least
      two independent reviewers using a standard form. The main outcome measure for
      comparing the effectiveness of tamsulosin with placebo, medical or surgical
      interventions was the change in urologic symptom scale scores. Secondary outcomes
      included changes in urinary flow measures (peak urine flow rate). The main
      outcome measure for adverse effects was the number of men reporting adverse
      effects. MAIN RESULTS: Fourteen studies involving 4122 subjects met inclusion
      criteria. Study duration ranged from 4 to 26 weeks, and no placebo-controlled
      study lasted longer than 13 weeks. The mean age of subjects was 64 years.
      Baseline symptom scores and urine flow rates demonstrated that men had moderate
      LUTS. Tamsulosin improved symptoms and peak urine flow relative to placebo. The
      weighted mean differences (WMD) for mean change from baseline for the Boyarsky
      symptom score for 0.4 mg and 0.8 mg doses of tamsulosin relative to placebo were 
      1.1 points (95% CI = -1.49 to -0.72; 12% improvement) and -1.6 points (95% CI = 
      2.3 to -1.0; 16% improvement), respectively. The WMD for mean change from
      baseline in peak urine flow were 1.1 mL/sec (95% CI = 0.59 to 1.51) and 1.1
      mL/sec (95% CI= 0.65 to 1.48) for 0.4 mg and 0.8 mg, respectively. Tamsulosin
      (0.2 mg to 0.4 mg) was as effective as other alpha antagonists and the
      phytotherapeutic agent Permixon(r) in improving symptoms and flow rates though
      the doses of all alpha-antagonists studied may not have been optimal.
      Discontinuations from treatment for any reason and discontinuations "due to
      adverse events" were similar in the low dose tamsulosin (0.2 mg) and placebo
      groups but increased to 16% in trials utilizing a 0.8 mg dose of tamsulosin. Low
      dose tamsulosin was generally well tolerated although not all the trials reported
      specific adverse events. The most frequently reported adverse events that were
      significantly greater than placebo included dizziness, rhinitis and abnormal
      ejaculation. Adverse effects increased markedly as tamsulosin dosing increased,
      and were reported in 75% of men receiving the 0.8 mg dose. Men receiving a 0.2 mg
      dose tamsulosin were less likely to discontinue treatment compared to men
      receiving terazosin. AUTHORS' CONCLUSIONS: Tamsulosin provided a small to
      moderate improvement in urinary symptoms and flow compared to men receiving
      placebo in men with BPH. Effectiveness was similar to other alpha antagonists and
      increased only slightly with higher doses. Long term effectiveness and ability to
      reduce complications due to BPH progression could not be determined. Adverse
      effects were generally mild but their frequency, including withdrawals, increased
      substantially with the higher doses that are generally available for treatment.

PMID- 21901682
TI  - WITHDRAWN: Primary prevention for alcohol misuse in young people.
AB  - BACKGROUND: Alcohol misuse is a cause of concern for health services, policy
      makers, prevention workers, the criminal justice system, youth workers, teachers
      and parents. OBJECTIVES: 1. To identify and summarize rigorous evaluations of
      psychosocial and educational interventions aimed at the primary prevention of
      alcohol misuse by young people. 2. To assess the effectiveness of primary
      prevention interventions over the longer-term (> 3 years). SEARCH STRATEGY:
      Databases searched (no time limits): Project CORK, BIDS, PSYCLIT, ERIC, ASSIA,
      MEDLINE, FAMILY-RESOURCES-DATABASE, HEALTH-PERIODICALS-DATABASE, EMBASE, BIDS,
      Dissertation-Abstracts, SIGLE, DRUG-INFO, SOMED, Social-Work-Abstracts, National
      Clearinghouse-on-Alcohol-and-Drug-Information, Mental-Health-Abstracts, DRUG
      database, ETOH (all searched Feb-June 2002). SELECTION CRITERIA: 1. randomised
      controlled and non-randomised controlled and interrupted time series designs. 2.
      educational and psychosocial primary prevention interventions for young people up
      to 25 years old. 3. alcohol-specific or generic (drugs; lifestyle) interventions
      providing alcohol outcomes reported. 4. alcohol outcomes: alcohol use, age of
      alcohol initiation, drinking 5+ drinks on any one occasion, drunkeness, alcohol
      related violence, alcohol related crime, alcohol related risky behaviour. DATA
      COLLECTION AND ANALYSIS: Stage 1: All papers screened by one reviewer against
      inclusion criteria. Stage 2: For those papers that passed Stage 1, key
      information was extracted from each paper by 2-3 reviewers. MAIN RESULTS: 20 of
      the 56 studies included showed evidence of ineffectiveness. No firm conclusions
      about the effectiveness of prevention interventions in the short- and medium-term
      were possible. Over the longer-term, the Strengthening Families Program (SFP)
      showed promise as an effective prevention intervention. The Number Needed to
      Treat (NNT) for the SFP over 4 years for three alcohol initiation behaviours
      (alcohol use, alcohol use without permission and first drunkeness) was 9 (for all
      three behaviours). One study also highlighted the potential value of culturally
      focused skills training over the longer-term (NNT=17 over three-and-a-half years
      for 4+ drinks in the last week). AUTHORS' CONCLUSIONS: 1. Research into important
      outcome variables needs to be undertaken. 2. Methodology of evaluations needs to
      be improved. 3. The Strengthening Families Programme needs to be evaluated on a
      larger scale and in different settings. 4. Culturally-focused interventions
      require further development and rigorous evaluation. 5. An international register
      of alcohol and drug misuse prevention interventions should be established and
      criteria agreed for rating prevention intervention in terms of safety, efficacy
      and effectiveness.

PMID- 21901683
TI  - Antihistamines and/or decongestants for otitis media with effusion (OME) in
      children.
AB  - BACKGROUND: This is an update of a Cochrane Review first published in The
      Cochrane Library in Issue 4, 2006.Otitis media with effusion (OME) is common and
      may cause hearing loss with associated developmental delay. Treatment remains
      controversial. The effectiveness of antihistamines, decongestants and
      antihistamine/decongestant combinations in promoting the resolution of effusions
      has been assessed by randomized controlled trials. OBJECTIVES: The objective of
      this review was to determine whether antihistamine, decongestant or combination
      therapy is effective in treating children who present with OME. SEARCH STRATEGY:
      We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register;
      the Cochrane Central Register of Controlled Trials (CENTRAL); PubMed; EMBASE;
      CINAHL; Web of Science; BIOSIS Previews; Cambridge Scientific Abstracts; ISRCTN
      and additional sources for published and unpublished trials. The date of the most
      recent search was 1 February 2011, following a previous search in 2006. SELECTION
      CRITERIA: Randomized controlled trials (RCTs) using antihistamines, decongestants
      or antihistamine/decongestant combinations as treatment for OME in children. We
      excluded trials that randomized on the basis of acute otitis media (AOM) even
      though OME was also studied in follow up. DATA COLLECTION AND ANALYSIS: Two
      authors independently extracted data from the published reports using
      standardized data extraction forms and methods. The two authors assessed the
      methodological quality of the included studies independently. We expressed
      dichotomous results as a risk ratio with 95% confidence intervals using a fixed
      effect model when homogeneous and a random-effects model when heterogeneous.
      Nearly all outcomes analyzed were homogeneous. We discussed continuous results
      qualitatively. We conducted statistical analysis using RevMan 5.1 software. MAIN
      RESULTS: Sixteen studies (1880 participants) were included in the review. No
      statistical or clinical benefit was found for any of the interventions or
      outcomes studied. However, treated study subjects experienced 11% more side
      effects than untreated subjects (number needed to treat to harm = 9). AUTHORS'
      CONCLUSIONS: The pooled data demonstrate no benefit and some harm from the use of
      antihistamines or decongestants alone or in combination in the management of OME,
      therefore we recommend against their use.

PMID- 21901684
TI  - Clotting factor concentrates given to prevent bleeding and bleeding-related
      complications in people with hemophilia A or B.
AB  - BACKGROUND: The hallmark of severe hemophilia is recurrent bleeding into joints
      and soft tissues with progressive joint damage, notwithstanding on-demand
      treatment. Prophylaxis has long been used but not universally adopted because of
      medical, psychosocial, and cost controversies. OBJECTIVES: To determine the
      effectiveness of clotting factor concentrate prophylaxis in the management of
      people with hemophilia A or B. SEARCH STRATEGY: We searched the Cochrane Cystic
      Fibrosis and Genetic Disorders Group's Coagulopathies Trials Register. In
      addition, we searched major electronic databases (MEDLINE, EMBASE, CENTRAL),
      handsearched relevant journals and abstract books and reference lists of relevant
      articles.Last search of Group's Coagulopathies Trials Register: 07 April 2011.
      SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled
      trials evaluating people with severe hemophilia A or hemophilia B receiving
      prophylactic clotting factor concentrates. DATA COLLECTION AND ANALYSIS: Two
      authors independently reviewed studies for eligibility, assessed risk of bias and
      extracted data. MAIN RESULTS: Six studies (including 142 participants) were
      eligible for inclusion. Two compared three-times-a-week prophylactic
      administration with on-demand treatment in children with hemophilia. Pooled
      results from these two studies showed a rate ratio of 0.30 (95% confidence
      interval; 0.12 to 0.76) for all bleedings and 0.22 (95% confidence interval 0.08
      to 0.63) for joint bleedings favouring prophylaxis. Results on the number of
      patients with preserved joints after three to seven years of follow-up were not
      pooled due to significant heterogeneity. Three of the remaining four studies
      evaluated hemophilia A; one showed a statistically significant decrease in
      frequency of joint bleeds with prophylaxis compared to placebo, with a rate
      difference of -10.73 (95% confidence interval -16.55 to -4.91) bleeds per year.
      Two studies compared two prophylaxis regimens, failing to demonstrate an
      advantage of one regimen over the other in terms of bleeding frequency. The
      fourth study evaluated hemophilia B and showed fewer joint bleeds with weekly (15
      IU/kg) versus bi-weekly (7.5 IU/kg) prophylaxis, rate difference -3.30 (95%
      confidence interval -5.50 to -1.10) bleeds per year. Non-significant increases in
      both inhibitor and infectious complications were observed in patients on
      prophylaxis, which occurred more often when using long-term venous access.
      AUTHORS' CONCLUSIONS: There is strong evidence from randomised controlled trials
      and observational trials that prophylaxis preserves joint function in children
      with hemophilia as compared to on-demand treatment. There is insufficient
      evidence from randomised controlled trials to confirm the observational evidence
      that prophylaxis decreases bleeding and related complications in patients with
      existing joint damage. Well-designed randomised controlled trials and prospective
      observational controlled studies are needed to establish the best prophylactic
      regimen and to assess the effectiveness of prophylactic clotting factor
      concentrates in adult patients.

PMID- 21901685
TI  - Antibiotics for ureaplasma in the vagina in pregnancy.
AB  - BACKGROUND: Preterm birth is a significant perinatal problem contributing to
      perinatal morbidity and mortality. Heavy vaginal ureaplasma colonisation is
      suspected of playing a role in preterm birth and preterm rupture of the
      membranes. Antibiotics are used to treat infections and have been used to treat
      pregnant women with preterm prelabour rupture of the membranes, resulting in some
      short-term improvements. However, the benefit of using antibiotics in early
      pregnancy to treat heavy vaginal colonisation is unclear. OBJECTIVES: To assess
      whether antibiotic treatment of pregnant women with heavy vaginal ureaplasma
      colonisation reduces the incidence of preterm birth and other adverse pregnancy
      outcomes. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth
      Group's Trials Register (31 May 2011). SELECTION CRITERIA: Randomised controlled
      trials comparing any antibiotic regimen with placebo or no treatment in pregnant
      women with ureaplasma detected in the vagina. DATA COLLECTION AND ANALYSIS: Three
      review authors independently assessed eligibility and trial quality and extracted
      data. MAIN RESULTS: We included one trial, involving 1071 women. Of these, 644
      women between 22 weeks and 32 weeks' gestation were randomly assigned to one of
      three groups of antibiotic treatment (n = 174 erythromycin estolate, n = 224
      erythromycin stearate, and n = 246 clindamycin hydrochloride) or a placebo (n =
      427). Preterm birth data was not reported in this trial. Incidence of low
      birthweight less than 2500 grams was only evaluated for erythromycin (combined, n
      = 398) compared to placebo (n = 427) and there was no statistically significant
      difference between the two groups (risk ratio (RR) 0.70, 95% confidence interval
      (CI) 0.46 to 1.07). There were no statistically significant differences in side
      effects sufficient to stop treatment between either group (RR 1.25, 95% CI 0.85
      to 1.85). AUTHORS' CONCLUSIONS: There is insufficient evidence to assess whether
      pregnant women who have vaginal colonisation with ureaplasma should be treated
      with antibiotics to prevent preterm birth.Preterm birth is a significant
      perinatal problem. Upper genital tract infections, including ureaplasmas, are
      suspected of playing a role in preterm birth and preterm rupture of the
      membranes. Antibiotics are used to treat women with preterm prelabour rupture of
      the membranes; this may result in prolongation of pregnancy and lowers the risks
      of maternal and neonatal infection. However, antibiotics may be beneficial
      earlier in pregnancy to eradicate potentially causative agents.

PMID- 21901686
TI  - WITHDRAWN: Terazosin for benign prostatic hyperplasia.
AB  - BACKGROUND: Lower urinary tract symptoms associated with benign prostatic
      obstruction (BPO) occur in up to 70% of men over the age of 60 years. To relieve
      these bothersome symptoms, treatment options include alpha-antagonists, also know
      as alpha-blockers. OBJECTIVES: We conducted a systematic review to evaluate the
      effectiveness and adverse effects of the alpha-blocker, terazosin, for treatment
      of urinary symptoms associated with BPO. SEARCH STRATEGY: Trials were searched in
      computerized general and specialized databases (MEDLINE, Cochrane Library), by
      checking bibliographies, and by contacting manufacturers and researchers.
      SELECTION CRITERIA: Studies were included if they (1) were randomized trials of
      at least 1 month duration, and (2) included men with symptomatic BPO and compared
      terazosin with placebo or active controls. DATA COLLECTION AND ANALYSIS: Study,
      patient characteristics and outcomes data were extracted in duplicate onto
      standardized forms utilizing a prospectively developed protocol. The main outcome
      measure for comparing the effectiveness of terazosin with placebo or other BPO
      medications was change in urological symptoms as measured by validated symptom
      scores. Secondary outcomes included urodynamic measures. The main outcome measure
      for adverse effects was the number of men reporting side effects. We also
      evaluated the number of men withdrawing from treatment and the number withdrawing
      due to adverse effects. MAIN RESULTS: Seventeen studies involving 5151 subjects
      met inclusion criteria (placebo-controlled (n = 10); alpha-blockers (n = 7);
      finasteride alone or in combination with terazosin as well as placebo (1);
      microwave therapy (TUMT) (1). Study duration ranged from 4 to 52 weeks. Mean age
      was 65 years and 82% of men were white. Baseline urologic symptom scale scores
      and flow rates demonstrated that men had moderate BPO. Efficacy outcomes were
      rarely reported in a fashion that allowed for data pooling but indicated that
      terazosin improved symptom scores and flow rates more than placebo or finasteride
      and similarly to other alpha antagonists. The pooled mean percentage improvements
      for the Boyarsky symptom score was 37% for terazosin versus 15% for placebo (n =
      4 studies). The mean percentage improvement for the American Urological
      Association symptom score (AUA) was 38% compared to 17% and 20% for placebo and
      finasteride, respectively (n = 2 studies). The pooled mean improvement in the
      International Prostate Symptom Score (IPSS) (40%) was similar to tamsulosin
      (43%). Peak urine flow rates improved greater with terazosin (22%), than placebo
      (11%) and finasteride (15%) but did not differ significantly from the other alpha
      blockers. The percentage of men discontinuing terazosin was comparable to men
      receiving placebo and finasteride but was greater then with other alpha
      antagonists. Adverse effects were greater than placebo and included dizziness,
      asthenia, headache, and postural hypotension. AUTHORS' CONCLUSIONS: The available
      evidence suggests that terazosin improves urinary symptoms and flow measures
      associated with BPO. Effectiveness is superior to placebo or finasteride, similar
      to other alpha-blockers but less than TUMT. Adverse effects were generally mild
      but more frequent than other alpha-blockers and associated with between a two-to
      four fold increase in treatment discontinuation.

PMID- 21901687
TI  - Combination contraceptives: effects on weight.
AB  - BACKGROUND: Weight gain is often considered a side effect of combination hormonal
      contraceptives, and many women and clinicians believe that an association exists.
      Concern about weight gain can limit the use of this highly effective method of
      contraception by deterring the initiation of its use and causing early
      discontinuation among users. However, a causal relationship between combination
      contraceptives and weight gain has not been established. OBJECTIVES: The aim of
      the review was to evaluate the potential association between combination
      contraceptive use and changes in weight. SEARCH STRATEGY: We searched the
      computerized databases CENTRAL (The Cochrane Library), MEDLINE, POPLINE, EMBASE,
      and LILACS for studies of combination contraceptives, as well as
      ClinicalTrials.gov and International Clinical Trials Registry Platform (ICTRP).
      Searches were conducted from January to May 2011. We also wrote to known
      investigators and manufacturers to request information about other published or
      unpublished trials not discovered in our search. SELECTION CRITERIA: All English
      language, randomized controlled trials were eligible if they had at least three
      treatment cycles and compared a combination contraceptive to a placebo or to a
      combination contraceptive that differed in drug, dosage, regimen, or study
      length. DATA COLLECTION AND ANALYSIS: All titles and abstracts located in the
      literature searches were assessed. Data were entered and analyzed with RevMan. A
      second author verified the data entered. For continuous data, we calculated the
      mean difference and 95% confidence interval (CI) for the mean change in weight
      between baseline and post-treatment measurements using a fixed-effect model. For
      categorical data, such as the proportion of women who gained or lost more than a
      specified amount of weight, the Peto odds ratio with 95% CI was calculated. MAIN
      RESULTS: We found 49 trials that met our inclusion criteria. The trials included
      85 weight change comparisons for 52 distinct contraceptive pairs (or placebos).
      The four trials with a placebo or no intervention group did not find evidence
      supporting a causal association between combination oral contraceptives or a
      combination skin patch and weight change. Most comparisons of different
      combination contraceptives showed no substantial difference in weight. In
      addition, discontinuation of combination contraceptives because of weight change
      did not differ between groups where this was studied. AUTHORS' CONCLUSIONS:
      Available evidence was insufficient to determine the effect of combination
      contraceptives on weight, but no large effect was evident. Trials to evaluate the
      link between combination contraceptives and weight change require a placebo or
      non-hormonal group to control for other factors, including changes in weight over
      time.

PMID- 21901688
TI  - Transfer of preterm infants from incubator to open cot at lower versus higher
      body weight.
AB  - BACKGROUND: A key criterion for discharging preterm infants home from nurseries
      is their ability to maintain temperature once transferred from incubators to open
      cots. The timing of transfer is important given the preterm infant's immature
      thermoregulatory mechanisms. OBJECTIVES: To determine the effects of body weight
      in transferring preterm infants from incubators to unheated open cots. SEARCH
      STRATEGY: Electronic databases, the Cochrane Central Register of Controlled
      Trials, clinical trials registers and the abstracts of the Society for Pediatric
      Research were searched. SELECTION CRITERIA: Randomised and quasi-randomised
      controlled trials comparing transfer of preterm infants from incubators to
      unheated open cots at lower and higher body weights. DATA COLLECTION AND
      ANALYSIS: Data collection and analysis was performed in accordance with the
      methods of the Cochrane Neonatal Review Group. MAIN RESULTS: Four eligible
      studies were identified. Two of the identified trials were assessed as having
      good methodological quality. Two studies reported daily weight gain (calculated
      as growth velocity); the lower body weight group had a significantly greater
      daily weight gain [pooled mean difference (MD) 2.66 (95% confidence interval
      (CI)1.37 to 3.95). One study reported a larger proportion of infants transferred
      at the higher body weight had an episode of low temperature in the first 72
      hours; while no difference between the two groups was found in the proportion of
      infants experiencing cold stress post-transfer to discharge. Two studies report
      no difference between the two groups in requiring an overhead heater for
      temperature maintenance [pooled RR 1.43 (95% CI 0.35 to 1.18). No statistically
      significant difference was shown for proportion of infants returning to an
      incubator [three studies (N = 336) [pooled RR 1.78 (95% CI 0.77 to 4.08].Two
      studies report there was no statistically significant difference in time spent in
      an open cot post transfer to discharge; while one study found infants transferred
      at lower weights had a significantly reduced length of stay [MD -9.00 (95% CI 
      13.29 to -4.71), a second study found no differences between the two groups [MD
      0.30 (95% CI -5.11 to 5.71). In these two studies not breastfeeding at discharge
      was not significantly different between the lower and higher body weight groups
      [pooled RR 1.02 (95% CI 0.69 to 1.51). AUTHORS' CONCLUSIONS: Medically stable
      preterm infants can be transferred to unheated open cots at a lower body weight
      of 1600 grams without adverse effects on temperature stability or weight gain.
      Earlier transfer does not necessarily result in earlier discharge.

PMID- 21901689
TI  - Non-invasive interventions for improving well-being and quality of life in
      patients with lung cancer.
AB  - BACKGROUND: This is an updated version of the original review published in Issue
      4, 2004 of The Cochrane Library. Lung cancer is one of the leading causes of
      death globally. Despite advances in treatment, the outlook for the majority of
      patients remains grim and most face a pessimistic future accompanied by sometimes
      devastating effects on emotional and psychological health. Although chemotherapy
      is accepted as an effective treatment for advanced lung cancer, the high
      prevalence of treatment-related side effects as well the symptoms of disease
      progression highlight the need for high-quality palliative and supportive care to
      minimise symptom distress and to promote quality of life. OBJECTIVES: To assess
      the effectiveness of non-invasive interventions delivered by healthcare
      professionals in improving symptoms, psychological functioning and quality of
      life in patients with lung cancer. SEARCH STRATEGY: We ran a search in February
      2011 to update the original completed review. We searched the Cochrane Central
      Register of Controlled Trials (The Cochrane Library 2011, Issue 2), MEDLINE
      (accessed through PubMed), EMBASE, PsycINFO, AMED, British Nursing Index and
      Archive (accessed through Ovid) and reference lists of relevant articles; we also
      contacted authors. SELECTION CRITERIA: Randomised or quasi-randomised clinical
      trials assessing the effects of non-invasive interventions in improving well
      being and quality of life in patients diagnosed with lung cancer. DATA COLLECTION
      AND ANALYSIS: Two authors independently assessed relevant studies for inclusion.
      Data extraction and risk of bias assessment of relevant studies was performed by
      one author and checked by a second author. MAIN RESULTS: Fifteen trials were
      included, six of which were added in this update. Three trials of a nursing
      intervention to manage breathlessness showed benefit in terms of symptom
      experience, performance status and emotional functioning. Four trials assessed
      structured nursing programmes and found positive effects on delay in clinical
      deterioration, dependency and symptom distress, and improvements in emotional
      functioning and satisfaction with care.Three trials assessed the effect of
      different psychotherapeutic, psychosocial and educational interventions in
      patients with lung cancer. One trial assessing counselling showed benefit for
      some emotional components of the illness but findings were not conclusive. One
      trial examined the effects of coaching sensory self monitoring and reporting on
      pain-related variables and found that although coaching increases the amount of
      pain data communicated to providers by patients with lung cancer, the magnitude
      of the effect is small and does not lead to improved efficacy of analgesics
      prescribed for each patient's pain level. One trial compared telephone-based
      sessions of either caregiver-assisted coping skills training (CST) or
      education/support involving the caregiver and found that patients in both
      treatment conditions showed improvements in pain, depression, quality of life and
      self efficacy.Two trials assessed exercise programmes; one found a beneficial
      effect on self empowerment and the other study showed an increase in quadriceps
      strength but no significant changes for any measure of quality of life. One trial
      of nutritional interventions found positive effects for increasing energy intake,
      but no improvement in quality of life. Two small trials of reflexology showed
      some positive but short-lasting effects on anxiety and pain intensity.The main
      limitations of the studies included were the variability of the interventions
      assessed and the approaches to measuring the considered outcomes, and the lack of
      data reported in the trials regarding allocation of patients to treatment groups
      and blinding. AUTHORS' CONCLUSIONS: Nurse follow-up programmes and interventions
      to manage breathlessness may produce beneficial effects. Counselling may help
      patients cope more effectively with emotional symptoms, but the evidence is not
      conclusive. Other psychotherapeutic, psychosocial and educational interventions
      can play some role in improving patients' quality of life. Exercise programmes
      and nutritional interventions have not shown relevant and lasting improvements of
      quality of life. Reflexology may have some beneficial effects in the short term.

PMID- 21901690
TI  - Stapled versus handsewn methods for ileocolic anastomoses.
AB  - BACKGROUND: Ileocolic anastomoses are commonly performed for right-sided colon
      cancer and Crohn's disease. The anastomosis may be constructed using a linear
      cutter stapler or by suturing. Individual trials comparing stapled versus
      handsewn ileocolic anastomoses have found little difference in the complication
      rate but they have lacked adequate power to detect potential small difference.
      This is an update of a Cochrane review first published in 2007. OBJECTIVES: To
      compare outcomes of ileocolic anastomoses performed using stapling and handsewn
      techniques. The hypothesis tested was that the stapling technique is associated
      with fewer complications. SEARCH STRATEGY: MEDLINE, EMBASE, Cochrane Colorectal
      Cancer Group specialised register SR-COLOCA, Cochrane Library were searched for
      randomised controlled trials comparing use of a linear cuter stapler with any
      type of suturing technique for ileocolic anastomoses in adults from 1970 to 2005
      and were updated in December 2010. Abstracts presented to the following society
      meetings between 1970 and 2010 were handsearched: American Society of Colon and
      Rectal Surgeons, the Association of Coloproctology of Great Britain and Ireland,
      European Association of Coloproctology. SELECTION CRITERIA: Randomised controlled
      trials comparing use of linear cutter stapler (isoperistaltic side to side or
      functional end to end) with any type of suturing technique in adults. DATA
      COLLECTION AND ANALYSIS: Eligible studies were selected and their methodological
      quality assessed. Relevant results were extracted and missing data sought from
      the authors. RevMan 5 was used to perform meta-analysis when there were
      sufficient data. Sub-group analyses for cancer inflammatory bowel disease as
      indication for ileocolic anastomoses were performed. MAIN RESULTS: After
      obtaining individual data from authors for studies that include other
      anastomoses, seven trials (including one unpublished) with 1125 ileocolic
      participants (441 stapled, 684 handsewn) were included. The five largest trials
      had adequate allocation concealment.Stapled anastomosis was associated with
      significantly fewer anastomotic leaks compared with handsewn (S=11/441,
      HS=42/684, OR 0.48 [0.24, 0.95] p=0.03). One study performed routine radiology to
      detect asymptomatic leaks. For the sub-group of 825 cancer patients in four
      studies, stapled anastomosis led to significantly fewer anastomotic leaks
      (S=4/300, HS=35/525, OR 0.28 [0.10, 0.75] p=0.01). In subgroup analysis of non
      cancer patients (3 studies, 264 patients) there were no differences for any
      reported outcomes. All other outcomes: stricture, anastomotic haemorrhage,
      anastomotic time, re-operation, mortality, intra-abdominal abscess, wound
      infection, length of stay, showed no significant difference. AUTHORS'
      CONCLUSIONS: Stapled functional end to end ileocolic anastomosis is associated
      with fewer leaks than handsewn anastomosis.

PMID- 21901691
TI  - Screening programmes for developmental dysplasia of the hip in newborn infants.
AB  - BACKGROUND: Uncorrected developmental dysplasia of the hip (DDH) is associated
      with long term morbidity such as gait abnormalities, chronic pain and
      degenerative arthritis. OBJECTIVES: To determine the effect of different
      screening programmes for DDH on the incidence of late presentation of congenital
      hip dislocation. SEARCH STRATEGY: Searches were performed in CENTRAL (The
      Cochrane Library), MEDLINE and EMBASE (January 2011) supplemented by searches of
      clinical trial registries, conference proceedings, cross references and
      contacting expert informants. SELECTION CRITERIA: Randomised, quasi-randomised or
      cluster trials comparing the effectiveness of screening programmes for DDH. DATA
      COLLECTION AND ANALYSIS: Three independent review authors assessed study
      eligibility and quality, and extracted data. MAIN RESULTS: No study examined the
      effect of screening (clinical and/or ultrasound) and early treatment versus not
      screening and later treatment.One study reported universal ultrasound compared to
      clinical examination alone did not result in a significant reduction in late
      diagnosed DDH or surgery but was associated with a significant increase in
      treatment.One study reported targeted ultrasound compared to clinical examination
      alone did not result in a significant reduction in late diagnosed DDH or surgery,
      with no significant difference in rate of treatment.Meta-analysis of two studies
      found universal ultrasound compared to targeted ultrasound did not result in a
      significant reduction in late diagnosed DDH or surgery. There was heterogeneity
      between studies reporting the effect on treatment rate.Meta-analysis of two
      studies found delayed ultrasound and targeted splinting compared to immediate
      splinting of infants with unstable (but not dislocated) hips resulted in no
      significant difference in the rate of late diagnosed DDH. Both studies reported a
      significant reduction in treatment with use of delayed ultrasound and targeted
      splinting.One study reported delayed ultrasound and targeted splinting compared
      to immediate splinting of infants with mild hip dysplasia on ultrasound resulted
      in no significant difference in late diagnosed DDH but a significant reduction in
      treatment. No infants in either group received surgery. AUTHORS' CONCLUSIONS:
      There is insufficient evidence to give clear recommendations for practice. There
      is inconsistent evidence that universal ultrasound results in a significant
      increase in treatment compared to the use of targeted ultrasound or clinical
      examination alone. Neither of the ultrasound strategies have been demonstrated to
      improve clinical outcomes including late diagnosed DDH and surgery. The studies
      are substantially underpowered to detect significant differences in the uncommon
      event of late detected DDH or surgery. For infants with unstable hips or mildly
      dysplastic hips, use of delayed ultrasound and targeted splinting reduces
      treatment without significantly increasing the rate of late diagnosed DDH or
      surgery.

PMID- 21901692
TI  - Antibiotic treatment for Clostridium difficile-associated diarrhea in adults.
AB  - BACKGROUND: Clostridium difficile is recognized as a frequent cause of antibiotic
      associated diarrhea and colitis. OBJECTIVES: The aim of this review is to
      investigate the efficacy of antibiotic therapy for C. difficile-associated
      diarrhea (CDAD). SEARCH STRATEGY: MEDLINE (1966 to March 24, 2010), EMBASE (1980
      to March 24, 2010), Cochrane Central Register of Controlled Trials and the
      Cochrane IBD/FBD Review Group Specialized Trials Register were searched using the
      following search terms: "pseudomembranous colitis and randomized trial";
      "Clostridium difficile and randomized trial"; "antibiotic associated diarrhea and
      randomized trial". SELECTION CRITERIA: Only randomized, controlled trials
      assessing antibiotic treatment for CDAD were included in the review. The
      following outcomes were sought: initial resolution of diarrhea; initial
      conversion of stool to cytotoxin and/or culture negative; recurrence of diarrhea;
      recurrence of fecal evidence of CDAD; patient response to cessation of prior
      antibiotic therapy; emergent surgery; and death. DATA COLLECTION AND ANALYSIS:
      Three authors independently assessed abstracts and full text articles for
      inclusion. The risk of bias was independently rated by two authors. For
      dichotomous outcomes, relative risks (RR) and 95% confidence intervals (CI) were
      derived from each study and summary statistics obtained when appropriate, using a
      fixed effects model, except where significant heterogeneity was detected, at
      which time a random effects model was used. MAIN RESULTS: Fifteen studies (total
      of 1152 participants) with CDAD were included. Nine different antibiotics were
      investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin,
      rifampin, rifaximin, bacitracin and fidaxomicin (OPT-80). Most of the studies
      were active comparator studies comparing vancomycin with other antibiotics. The
      risk of bias was rated as high for 12 of 15 included studies. Patients with
      severe CDAD were often excluded from the included studies. In the only placebo
      controlled trial vancomycin was found to be superior to placebo for treatment of
      CDAD for initial symptomatic cure. Initial symptomatic cure was achieved in 41%
      of vancomycin patients compared to 4% of placebo patients (1 study; 44 patients;
      RR 9.00; 95% CI 1.24 to 65.16). Vancomycin was significantly superior to placebo
      for initial bacteriologic response. Initial bacteriologic response was achieved
      in 45% of vancomycin patients compared to 4% of placebo patients (1 study; 44
      patients; RR 10.00; 95% CI 1.40 to 71.62). The results of this study should be
      interpreted with caution due to the small number of patients and high risk of
      bias. No statistically significant differences in efficacy were found between
      vancomycin and metronidazole, vancomycin and fusidic acid, vancomycin and
      nitazoxanide, or vancomycin and rifaximin. No statistically significant
      differences in efficacy were found between metronidazole and nitazoxanide or
      metronidazole and fusidic acid. Vancomycin was significantly superior to
      bacitracin for initial bacteriologic response. Initial bacteriologic response was
      achieved in 48% of vancomycin patients compared to 25% of bacitracin patients (2
      studies; 104 patients; RR 0.52; 95% CI 0.31 to 0.86). Teicoplanin, an antibiotic
      of limited availability and great cost, was significantly superior to vancomycin
      for initial bacteriologic response and cure. Initial bacteriologic response was
      achieved in 62% of vancomycin patients compared to 87% of teicoplanin patients (2
      studies; 110 patients; RR 1.43; 95% CI 1.14 to 1.81). Bacteriologic cure was
      achieved in 45% of vancomycin patients compared to 82% of teicoplanin patients (2
      studies; 110 patients; RR 1.82; 95% CI 1.19 to 2.78). These results should be
      interpreted with caution due to the small number of patients and the high risk of
      bias in the two studies in the pooled analysis. Teicoplanin was significantly
      superior to metronidazole for initial bacteriologic response. Initial
      bacteriologic response was achieved in 71% of metronidazole patients compared to
      93% of teicoplanin patients (1 study; 59 patients; RR 0.76; 95% CI 0.60 to 0.98).
      This result should be interpreted with caution due to the small number of
      patients and high risk of bias in the study. Only one study investigated
      synergistic antibiotic combination, metronidazole and rifampin, and no advantage
      was demonstrated for the drug combination. This result should be interpreted with
      caution due to the small number of patients and high risk of bias in the study.
      Adverse events including surgery and death occurred infrequently in the included
      studies. There was a total of 18 deaths among 1152 patients in this systematic
      review. Among the studies that commented on the cause of mortality the deaths
      were attributed to underlying disease rather than CDAD or antibiotic treatment.
      One study reported a partial colectomy after failed CDAD treatment. AUTHORS'
      CONCLUSIONS: Current evidence leads to uncertainty whether mild CDAD needs to be
      treated. The studies provide little evidence for antibiotic treatment of severe
      CDAD as many studies excluded these patients. Considering the two goals of
      therapy: improvement of the patient's clinical condition and prevention of spread
      of C. difficile infection to other patients, one should choose the antibiotic
      that brings both symptomatic cure and bacteriologic cure. A recommendation to
      achieve these goals cannot be made because of the small numbers of patients in
      the included studies and the high risk of bias in these studies, especially
      related to dropouts. Most of the active comparator studies found no statistically
      significant difference in efficacy between vancomycin and other antibiotics
      including metronidazole, fusidic acid, nitazoxanide or rifaximin. Teicoplanin may
      be an attractive choice but for its limited availability (Teicoplanin is not
      available in the USA) and great cost relative to the other options. More research
      of antibiotic treatment and other treatment modalities of CDAD is required.

PMID- 21901693
TI  - Placental cord drainage after vaginal delivery as part of the management of the
      third stage of labour.
AB  - BACKGROUND: Cord drainage in the third stage of labour involves unclamping the
      previously clamped and divided umbilical cord and allowing the blood from the
      placenta to drain freely into an appropriate receptacle. OBJECTIVES: The
      objective of this review was to assess the specific effects of placental cord
      drainage on the third stage of labour following vaginal birth, with or without
      prophylactic use of uterotonics in the management of the third stage of labour.
      SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (February 2010). SELECTION CRITERIA: Randomised controlled trials
      comparing placental cord draining with no placental cord drainage as part of the
      management of the third stage of labour. DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed the quality of trials and extracted data. This was
      then verified by the third review author who then entered the agreed outcomes to
      the review. MAIN RESULTS: Three studies involving 1257 women met our inclusion
      criteria. Cord drainage reduced the length of the third stage of labour (mean
      difference (MD) -2.85 minutes, 95% confidence interval (CI) -4.04 to -1.66; three
      trials, 1257 women (heterogeneity: T2 = 0.87; Chi2P=17.19, I2 = 88%)) and reduced
      the average amount of blood loss (MD -77.00 ml, 95% CI -113.73 to -40.27; one
      trial, 200 women).No incidence of retained placenta at 30 minutes after birth was
      observed in the included studies, therefore, it was not possible to compare this
      outcome. The differences between the cord drainage and the control group were not
      statistically significant for postpartum haemorrhage or manual removal of the
      placenta. None of the included studies reported fetomaternal transfusion outcomes
      and there were no data relating to maternal pain or discomfort during the third
      stage of labour. AUTHORS' CONCLUSIONS: There was a small reduction in the length
      of the third stage of labour and also in the amount of blood loss when cord
      drainage was applied compared with no cord drainage. The clinical importance of
      such observed statistically significant reductions, is open to debate. There is
      no clear difference in the need for manual removal of placenta, blood transfusion
      or the risk of postpartum haemorrhage. Due to small trials with medium risk of
      bias, the results should be interpreted with caution.

PMID- 21901694
TI  - Reminder packaging for improving adherence to self-administered long-term
      medications.
AB  - BACKGROUND: Current methods of improving medication adherence for health problems
      are mostly complex, labour-intensive, and not reliably effective. Medication
      'reminder packaging', which incorporates a date or time for a medication to be
      taken in the packaging, can act as a reminder to improve adherence. This review
      of reminder packaging is an update of our 2006 Cochrane review. OBJECTIVES: The
      objective of this review was to determine the effects of reminder packaging aids
      for self-administered medication/s taken for at least one month, on adherence and
      other outcomes. SEARCH STRATEGY: We updated searches of the Cochrane Central
      Register of Controlled Trials (CENTRAL) and the Database of Abstracts of Reviews
      of Effects (DARE) (The Cochrane Library Issue 9, 2010), MEDLINE, EMBASE, CINAHL
      and PsycINFO from the database start dates to September 2010. We searched Current
      Controlled Trials to identify trials in progress. We performed a cited reference
      search on the Science Citation Index to identify papers that had cited the
      original systematic review.We also searched the Internet, contacted packaging
      manufacturers, and checked abstracts from the Pharm-line database and reference
      lists from relevant articles. We did not apply any language restrictions.
      SELECTION CRITERIA: We selected randomised controlled trials with at least 80%
      follow up. We intended to do a sensitivity analysis of those studies that
      analysed their data on an intention-to-treat basis. Included studies compared a
      reminder packaging device with no device, for participants taking self
      administered medications for at least one month. DATA COLLECTION AND ANALYSIS:
      Three review authors independently assessed studies for inclusion, assessed
      quality, and extracted data from included studies. Where considered appropriate,
      data were combined for meta-analysis, or were reported and discussed in a
      narrative. MAIN RESULTS: We included twelve studies containing data on 2196
      participants; four of these studies were newly included in this 2011 update of
      our 2006 Cochrane review.Six intervention groups in four trials provided data on
      the percentage of pills taken. Reminder packaging increased the percentage of
      pills taken (mean difference (MD) 11% (95% confidence interval (CI) 6% to 17%)).
      Notable heterogeneity occurred among these trials (I(2) = 96.3%). Two trials
      provided data for the proportion of self-reported adherent patients, reporting a
      reduction in the intervention group which was not statistically significant (odds
      ratio = 0.89 (95% CI 0.56 to 1.40)). We conducted meta-analysis on data from two
      trials assessing the effect of reminder packaging on blood pressure measurements.
      We found that reminder packaging significantly decreased diastolic blood pressure
      (MD = -5.89 mmHg (95% CI -6.70 to -5.09; P < 0.00001; I(2) = 0%). No effect was
      seen on systolic blood pressure (mean change -1.01, 95% CI -2.22 to 0.20; P =
      0.1, I(2) = 0%). We also conducted meta-analysis on extracted data from two
      trials that looked at change in glycated haemoglobin. We found that reminder
      packaging significantly reduced glycated haemoglobin levels (MD -0.72; 95% CI 
      0.83 to -0.60; P < 0.00001; I(2) = 92%), although there was considerable
      heterogeneity.No appropriate data were available for meta-analysis of remaining
      clinical outcomes, which included serum vitamin C and E levels, and self-reported
      psychological symptoms (one trial each). We reported remaining data narratively.
      In one study the presence of a reminder packaging aid was found to be preferred
      by patients with low literacy levels. AUTHORS' CONCLUSIONS: Reminder packing may
      represent a simple method for improving adherence for patients with selected
      conditions. Further research is warranted to improve the design and targeting of
      these devices.

PMID- 21901695
TI  - Psychosocial and pharmacological treatments versus pharmacological treatments for
      opioid detoxification.
AB  - BACKGROUND: Different pharmacological approaches aimed at opioid detoxification
      are effective. Nevertheless a majority of patients relapse to heroin use, and
      relapses are a substantial problem in the rehabilitation of heroin users. Some
      studies have suggested that the sorts of symptoms which are most distressing to
      addicts during detoxification are psychological rather than physiological
      symptoms associated with the withdrawal syndrome. OBJECTIVES: To evaluate the
      effectiveness of any psychosocial plus any pharmacological interventions versus
      any pharmacological alone for opioid detoxification, in helping patients to
      complete the treatment, reduce the use of substances and improve health and
      social status. SEARCH STRATEGY: We searched the Cochrane Drugs and Alcohol Group
      trials register (June 2011), Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library Issue 6, 2011), PUBMED (1996 to June 2011);
      EMBASE (January 1980 to June 2011); CINAHL (January 2003 to June 2008); PsycINFO
      (1985 to April 2003) and reference list of articles. SELECTION CRITERIA:
      Randomised controlled trials and controlled clinical trial which focus on any
      psychosocial associated with any pharmacological intervention aimed at opioid
      detoxification. People less than 18 years of age and pregnant women were
      excluded. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials
      quality and extracted data. MAIN RESULTS: Eleven studies, 1592 participants,
      fulfilled the criteria of inclusion and were included in the review. The studies
      considered five different psychosocial interventions and two pharmacological
      treatments (methadone and buprenorphine). Compared to any pharmacological
      treatment alone, the association of any psychosocial with any pharmacological was
      shown to significantly reduce dropouts RR 0.71 (95% CI 0.59 to 0.85), use of
      opiate during the treatment, RR 0.82 (95% CI 0.71 to 0.93), at follow up RR 0.66
      (95% IC 0.53 to 0.82) and clinical absences during the treatment RR 0.48 (95%CI
      0.38 to 0.59). Moreover, with the evidence currently available, there are no data
      supporting a single psychosocial approach. AUTHORS' CONCLUSIONS: Psychosocial
      treatments offered in addition to pharmacological detoxification treatments are
      effective in terms of completion of treatment, use of opiate, participants
      abstinent at follow-up and clinical attendance. The evidence produced by this
      review is limited due to the small number of participants included in the
      studies, the heterogeneity of the assessment or the lack of detailed outcome
      information that prevented the possibility of cumulative analysis for several
      outcomes. Nevertheless it seems desirable to develop adjunct psychosocial
      approaches that might make detoxification more effective.

PMID- 21901696
TI  - Interventions to promote the wearing of hearing protection.
AB  - BACKGROUND: This is an update of a Cochrane Review first published in The
      Cochrane Library in Issue 2, 2006 and previously updated in 2009.Noise-induced
      hearing loss can be prevented by eliminating or lowering noise exposure levels.
      Where the source of the noise cannot be eliminated, workers have to rely on
      hearing protection equipment. Several trials have been conducted to study the
      effectiveness of interventions to influence the wearing of hearing protection.
      OBJECTIVES: To evaluate the effectiveness of interventions to enhance the wearing
      of hearing protection among persons regularly exposed to high noise levels.
      SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group
      Trials Register; the Cochrane Central Register of Controlled Trials (CENTRAL)
      (The Cochrane Library 2011, Issue 1); PubMed; EMBASE; CINAHL; Web of Science;
      BIOSIS Previews; Cambridge Scientific Abstracts; ICTRP and additional sources for
      published and unpublished trials. The date of the most recent search was 8 April
      2011. SELECTION CRITERIA: We included studies if they had a randomised design, if
      they were among noise exposed (> 80 dB(A)) persons, if they included an
      intervention to promote the wearing of hearing protection (compared to another
      intervention or no intervention), and if the outcome measured was the amount of
      use of hearing protection or a proxy measure thereof. DATA COLLECTION AND
      ANALYSIS: Two authors selected relevant trials, assessed risk of bias and
      extracted data. MAIN RESULTS: Seven studies, involving 4670 participants, were
      included.A computer-based intervention lasting 30 minutes, tailored to the risk
      of an individual worker, was not found to be more effective than a video
      providing general information among workers, around 80% of whom already used
      hearing protection.A four-year school-based hearing loss prevention programme
      found that the intervention group was twice as likely to wear some kind of
      hearing protection as the control group that received a baseline hearing test and
      two additional tests at years two and three.We conducted two meta-analyses for
      the comparisons 'tailored strategy (the use of communication or other types of
      interventions that are specific to an individual or a group and aim to change
      behaviour) versus non-tailored strategy' and 'tailored strategy versus a
      commercial video on the use of hearing protection' to look at mean percentage use
      of hearing protective devices (HPDs), that showed improvement in the mean use of
      HPDs for the tailored group. A meta-analysis of the comparison 'mixed
      interventions' (classroom instruction, distribution of HPDs, mailings, noise
      level assessments and audiometric testing) versus control (audiometric testing
      alone) also showed improvement in self reported use of HPDs when shooting
      firearms.Tailored education showed an improvement in HPD use of 8.3% versus
      targeted education (6.1%). AUTHORS' CONCLUSIONS: The evidence found in this
      review shows that some interventions improve the mean use of hearing protection
      devices compared to non-intervention. Future trials should have standard outcomes
      and interventions to allow the combining of results in meta-analysis.

PMID- 21901697
TI  - Insulin for glycaemic control in acute ischaemic stroke.
AB  - BACKGROUND: Patients with hyperglycaemia concomitant with an acute stroke have
      greater stroke severity and greater functional impairment when compared to those
      with normoglycaemia at stroke presentation. OBJECTIVES: To determine whether
      maintaining serum glucose within a specific normal range (4 to 7.5 mmol/L) in the
      first 24 hours of acute ischaemic stroke influences outcome. SEARCH STRATEGY: We
      searched the Cochrane Stroke Group Trials Register (June 2010), CENTRAL (The
      Cochrane Library 2010, Issue 2), MEDLINE (1950 to June 2010), EMBASE (1980 to
      June 2010), CINAHL (1982 to June 2010), Science Citation Index (1900 to June
      2010), and Web of Science (ISI Web of Knowledge) (1993 to June 2010). In an
      effort to identify further published, unpublished and ongoing trials we searched
      ongoing trials registers and SCOPUS. SELECTION CRITERIA: Eligible studies were
      randomised controlled trials comparing intensively monitored insulin therapy
      versus usual care in adult patients with acute ischaemic stroke. DATA COLLECTION
      AND ANALYSIS: Two review authors independently extracted the study
      characteristics, study quality, and data to estimate the odds ratio (OR) and 95%
      confidence interval (CI), mean difference (MD) and standardised mean difference
      (SMD) of outcome measures. MAIN RESULTS: We included seven trials involving 1296
      participants (639 participants in the intervention group and 657 in the control
      group). We found that there was no difference between treatment and control
      groups in the outcome of death or disability and dependence (OR 1.00, 95% CI 0.78
      to 1.28) or final neurological deficit (SMD -0.12, 95% CI -0.23 to 0.00). The
      rate of symptomatic hypoglycaemia was higher in the intervention group (OR 25.9,
      95% CI 9.2 to 72.7). In the subgroup analyses of diabetes mellitus (DM) versus
      non-DM, we found no difference for the outcomes of death and dependency or
      neurological deficit. AUTHORS' CONCLUSIONS: With the current evidence, we found
      that the administration of intravenous insulin with the objective of maintaining
      serum glucose within a specific range in the first hours of acute ischaemic
      stroke does not provide benefit in terms of functional outcome, death, or
      improvement in final neurological deficit and significantly increased the number
      of hypoglycaemic episodes. Specifically, those who were maintained within a more
      tight range of glycaemia with intravenous insulin experienced a greater risk of
      symptomatic and asymptomatic hypoglycaemia than those individuals in the control
      group.

PMID- 21901698
TI  - Pressure-relieving devices for treating heel pressure ulcers.
AB  - BACKGROUND: Pressure ulcers are areas of localised damage to the skin and
      underlying tissue caused by pressure or shear. Pressure redistribution devices
      are used as part of the treatment to reduce the pressure on the ulcer. The
      anatomy of the heel and the susceptibility of the foot to vascular disease mean
      that pressure ulcers located there require a particular approach to pressure
      relief. OBJECTIVES: To determine the effects of pressure-relieving interventions
      for treating pressure ulcers on the heel. SEARCH STRATEGY: We searched the
      Cochrane Wounds Group Specialised Register (searched 25 March 2011); The Cochrane
      Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue
      1); Ovid MEDLINE (1948 to March Week 3 2011); Ovid EMBASE (1980 to 2011 Week
      12);Ovid MEDLINE (In-Process & Other Non-Indexed Citations March 29, 2011); and
      EBSCO CINAHL (1982 to 25 March 2011). We applied no language or publication date
      restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs)
      that compared the effects of pressure-relieving devices on the healing of
      pressure ulcers of the heel. Participants were treated in any care setting.
      Interventions were any pressure-relieving devices including mattresses and
      specific heel devices. DATA COLLECTION AND ANALYSIS: Both review authors
      independently reviewed titles and abstracts and selected studies for inclusion.
      Both review authors independently extracted data and assessed studies for risk of
      bias. MAIN RESULTS: One study met the inclusion criteria. This study (141
      participants) compared two mattress systems however losses to follow up were too
      great to permit reliable conclusions. AUTHORS' CONCLUSIONS: This review
      identified one small study at moderate to high risk of bias which provided no
      evidence to inform practice. More research is needed.

PMID- 21901699
TI  - Antiemetics for reducing vomiting related to acute gastroenteritis in children
      and adolescents.
AB  - BACKGROUND: Vomiting is a common manifestation of acute gastroenteritis in
      children and adolescents. When untreated it can be a hindrance to oral
      rehydration therapy, which is the cornerstone in the management of acute
      gastroenteritis. Evidence is needed concerning the safety and efficacy of
      antiemetic use for vomiting in acute gastroenteritis in children. OBJECTIVES: To
      assess the safety and effectiveness of antiemetics on gastroenteritis induced
      vomiting in children and adolescents. SEARCH STRATEGY: We searched the Cochrane
      Upper Gastrointestinal and Pancreatic Diseases Group Trials Register comprising
      references identified from comprehensive electronic database searches and hand
      searches of relevant journals and abstract books of conferences.The search was re
      run and is up to date as on 20 July 2010. SELECTION CRITERIA: Randomized
      controlled trials comparing antiemetics with placebo or no treatment, in children
      and adolescents under the age of 18, for vomiting due to gastroenteritis. DATA
      COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality
      and extracted data. MAIN RESULTS: We included seven trials involving 1,020
      participants. Mean time to cessation of vomiting in one study was 0.34 days less
      with dimenhydrinate suppository compared to placebo (P value = 0.036). Pooled
      data from three studies comparing oral ondansetron with placebo showed: a
      reduction in the immediate hospital admission rate (RR 0.40, NNT 17, 95% CI 10 to
      100) but no difference between the hospitalization rates at 72 hours after
      discharge from the Emergency Department (ED); a reduction in IV rehydration rates
      both during the ED stay (RR 0.41, NNT 5, 95% CI 4 to 8), and in follow-up to 72
      hours after discharge from the ED stay (worst-best scenario for ondansetron RR
      0.57, NNT 6, 95% CI 4 to 13) and an increase in the proportion of patients with
      cessation of vomiting (RR 1.34, NNT 5, 95% CI 3 to 7)). No significant difference
      was noted in the revisit rates or adverse events, although diarrhea was reported
      as a side effect in four of the five ondansetron studies. In one study the
      proportion of patients with cessation of vomiting in 24 hours was (58%) with IV
      ondansetron, (17%) placebo and (33%) in the metoclopramide group (P value =
      0.039). AUTHORS' CONCLUSIONS: Oral ondansetron increased the proportion of
      patients who had ceased vomiting and reduced the number needing intravenous
      rehydration and immediate hospital admission. Intravenous ondansetron and
      metoclopramide reduced the number of episodes of vomiting and hospital admission,
      and dimenhydrinate as a suppository reduced the duration of vomiting.

PMID- 21901700
TI  - Patellar tendon versus hamstring tendon autograft for anterior cruciate ligament
      rupture in adults.
AB  - BACKGROUND: Reconstruction of the anterior cruciate ligament (ACL) commonly
      involves patellar tendon (PT) or hamstring tendon(s) (HT) autografts. There is no
      consensus with respect to the choice between these two grafts in ACL surgery.
      OBJECTIVES: This review compared the outcomes of ACL reconstruction using PT
      versus HT autografts in ACL deficient patients. SEARCH STRATEGY: We searched the
      Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (April 2008),
      the Cochrane Central Register of Controlled Trials (2008, Issue 2), MEDLINE (1966
      to April 10 2008), EMBASE (1980 to April 10 2008), conference proceedings and
      reference lists. No language restrictions were applied. SELECTION CRITERIA:
      Randomized and quasi-randomized controlled trials comparing outcomes (minimum two
      year follow-up) following ACL reconstruction using either PT or HT autografts in
      skeletally mature adults, irrespective of the number of bundles, fixation method
      or incision technique. DATA COLLECTION AND ANALYSIS: After independent study
      selection, the four authors independently assessed trial quality and risk of
      bias, and extracted data using pre-developed forms. Trial authors were contacted
      for additional data and information. Risk ratios with 95% confidence intervals
      were calculated for dichotomous outcomes, and mean differences and 95% confidence
      intervals for continuous outcomes. MAIN RESULTS: Nineteen trials providing
      outcome data for 1597 young to middle-aged adults were included. Many trials were
      at high risk of bias reflecting inadequate methods of randomization, lack of
      blinding and incomplete assessment of outcome.Pooled data for primary outcomes,
      reported in a minority of trials, showed no statistically significant differences
      between the two graft choices for functional assessment (single leg hop test),
      return to activity, Tegner and Lysholm scores, and subjective measures of
      outcome. There were also no differences found between the two interventions for
      re-rupture or International Knee Documentation Committee scores. There were
      inadequate long-term results, such as to assess the development of
      osteoarthritis.All tests (instrumental, Lachman, pivot shift) for static
      stability consistently showed that PT reconstruction resulted in a more
      statically stable knee compared with HT reconstruction. Conversely, patients
      experienced more anterior knee problems, especially with kneeling, after PT
      reconstruction. PT reconstructions resulted in a statistically significant loss
      of extension range of motion and a trend towards loss of knee extension strength.
      HT reconstructions demonstrated a trend towards loss of flexion range of motion
      and a statistically significant loss of knee flexion strength. The clinical
      importance of the above range of motion losses is unclear. AUTHORS' CONCLUSIONS:
      There is insufficient evidence to draw conclusions on differences between the two
      grafts for long-term functional outcome. While PT reconstructions are more likely
      to result in statically stable knees, they are also associated with more anterior
      knee problems.

PMID- 21901701
TI  - Oral contraceptives for functional ovarian cysts.
AB  - BACKGROUND: Functional ovarian cysts are a common gynecological problem among
      women of reproductive age worldwide. When large, persistent, or painful, these
      cysts may require operations, sometimes resulting in removal of the ovary. Since
      early oral contraceptives were associated with a reduced incidence of functional
      ovarian cysts, many clinicians inferred that birth control pills could be used to
      treat cysts as well. This became a common clinical practice in the early 1970s.
      OBJECTIVES: This review examined all randomized controlled trials that studied
      oral contraceptives as therapy for functional ovarian cysts. SEARCH STRATEGY: We
      searched the databases of CENTRAL, MEDLINE, POPLINE, and EMBASE, as well as
      clinical trials databases (ClinicalTrials.gov and ICTRP). We also examined the
      reference lists of articles and wrote to authors of identified trials to seek
      articles we had missed. SELECTION CRITERIA: We included randomized controlled
      trials in any language that included oral contraceptives used for treatment and
      not prevention of functional ovarian cysts. Criteria for diagnosis of cysts were
      those used by authors of trials. DATA COLLECTION AND ANALYSIS: Two authors
      independently abstracted data from the articles. One entered the data into RevMan
      and a second verified accuracy of data entry. For dichotomous outcomes, we
      computed the Mantel-Haenszel odds ratio with 95% confidence interval (CI). For
      continuous outcomes, we calculated the mean difference with 95% CI. MAIN RESULTS:
      We identified eight randomized controlled trials from four countries; the studies
      included a total of 686 women. Treatment with combined oral contraceptives did
      not hasten resolution of functional ovarian cysts in any trial. This held true
      for cysts that occurred spontaneously as well as those that developed after
      ovulation induction. Most cysts resolved without treatment within a few cycles;
      persistent cysts tended to be pathological (e.g., endometrioma or para-ovarian
      cyst) and not physiological. AUTHORS' CONCLUSIONS: Although widely used for
      treating functional ovarian cysts, combined oral contraceptives appear to be of
      no benefit. Watchful waiting for two or three cycles is appropriate. Should cysts
      persist, surgical management is often indicated.

PMID- 21901702
TI  - Interventions for latent autoimmune diabetes (LADA) in adults.
AB  - BACKGROUND: Latent autoimmune diabetes in adults (LADA) is a slowly developing
      type 1 diabetes. OBJECTIVES: To compare interventions used for LADA. SEARCH
      STRATEGY: Studies were obtained from searches of electronic databases,
      supplemented by handsearches, conference proceedings and consultation with
      experts. Date of last search was December 2010. SELECTION CRITERIA: Randomised
      controlled trials (RCT) and controlled clinical trials (CCT) evaluating
      interventions for LADA or type 2 diabetes with antibodies were included. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed
      risk of bias. Studies were summarised using meta-analysis or descriptive methods.
      MAIN RESULTS: Searches identified 13,306 citations. Fifteen publications (ten
      studies) were included, involving 1019 participants who were followed between
      three months to 10 years (1060 randomised). All studies had a high risk of bias.
      Sulphonylurea (SU) with insulin did not improve metabolic control significantly
      more than insulin alone at three months (one study, n = 15) and at 12 months (one
      study, n = 14) of treatment and follow-up. SU (with or without metformin) gave
      poorer metabolic control compared to insulin alone (mean difference in
      glycosylated haemoglobin A1c (HbA1c) from baseline to end of study, for insulin
      compared to oral therapy: -1.3% (95% confidence interval (CI) -2.4 to -0.1; P =
      0.03, 160 participants, four studies, follow-up/duration of therapy: 12, 30, 36
      and 60 months; however, heterogeneity was considerable). In addition, there was
      evidence that SU caused earlier insulin dependence (proportion requiring insulin
      at two years was 30% in the SU group compared to 5% in conventional care group (P
      < 0.001); patients classified as insulin dependent was 64% (SU group) and 12.5%
      (insulin group, P = 0.007). No intervention influenced fasting C-peptide, but
      insulin maintained stimulated C-peptide better than SU (one study, mean
      difference 7.7 ng/ml (95% CI 2.9 to 12.5)). In a five year follow-up of GAD65
      (glutamic acid decarboxylase formulated with aluminium hydroxide), improvements
      in fasting and stimulated C-peptide levels (20 MUg group) were maintained after
      five years. Short term (three months) follow-up in one study (n = 74) using
      Chinese remedies did not demonstrate a significant difference in improving
      fasting C-peptide levels compared to insulin alone (0.07 ug/L (95% CI -0.05 to
      0.19). One study using vitamin D with insulin showed steady fasting C-peptide
      levels in the vitamin D group but declining fasting C-peptide levels (368 to 179
      pmol/L, P = 0.006) in the insulin alone group at 12 months follow-up. Comparing
      studies was difficult as there was a great deal of heterogeneity in the studies
      and in their selection criteria. There was no information regarding health
      related quality of life, complications of diabetes, cost or health service
      utilisation, mortality and limited evidence on adverse events (studies on oral
      agents or insulin reported no adverse events in terms of severe hypoglycaemic
      episodes). AUTHORS' CONCLUSIONS: Two studies show SU leading to earlier insulin
      dependence and a meta-analysis of four studies with considerable heterogeneity
      showed poorer metabolic control if SU is prescribed for patients with LADA
      compared to insulin. One study showed that vitamin D with insulin may protect
      pancreatic beta cells in LADA. Novel treatments such as GAD65 in certain doses
      (20 MUg) have been suggested to maintain fasting and stimulated C-peptide levels.
      However, there is no significant evidence for or against other lines of treatment
      of LADA.

PMID- 21901703
TI  - Interventions for the treatment of oral and oropharyngeal cancers: surgical
      treatment.
AB  - BACKGROUND: Surgery is an important part of the management of oral cavity cancer
      with regard to both the removal of the primary tumour and removal of lymph nodes
      in the neck. Surgery is less frequently used in oropharyngeal cancer. Surgery
      alone may be treatment for early stage disease or surgery may be used in
      combination with radiotherapy, chemotherapy and immunotherapy/biotherapy. There
      is variation in the recommended timing and extent of surgery in the overall
      treatment regimens of people with these cancers. OBJECTIVES: To determine which
      surgical treatment modalities for oral cavity and oropharyngeal cancers result in
      increased overall survival, disease free survival, progression free survival and
      reduced recurrence. SEARCH STRATEGY: The following electronic databases were
      searched: the Cochrane Oral Health Group Trials Register (to 17 February 2011),
      the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library 2011, Issue 1), MEDLINE via OVID (1950 to 17 February 2011) and EMBASE
      via OVID (1980 to 17 February 2011). There were no restrictions regarding
      language or date of publication. SELECTION CRITERIA: Randomised controlled trials
      where more than 50% of participants had primary tumours of the oral cavity or
      oropharynx, and which compared two or more surgical treatment modalities or
      surgery versus other treatment modalities. DATA COLLECTION AND ANALYSIS: Data
      extraction and assessment of risk of bias was undertaken independently by two or
      more review authors. Study authors were contacted for additional information as
      required. Adverse events data were collected from published trials. MAIN RESULTS:
      Seven trials (n = 669; 667 with cancers of the oral cavity) satisfied the
      inclusion criteria, but none were assessed as low risk of bias. Trials were
      grouped into three main comparisons. Four trials compared elective neck
      dissection (ND) with therapeutic neck dissection in patients with oral cavity
      cancer and clinically negative neck nodes, but differences in type of surgery and
      duration of follow-up made meta-analysis inappropriate. Three of these trials
      reported overall and disease free survival. One trial showed a benefit for
      elective supraomohyoid neck dissection compared to therapeutic ND in overall and
      disease free survival. Two trials found no difference between elective radical ND
      and therapeutic ND for the outcomes of overall survival and disease free
      survival. All four trials found reduced locoregional recurrence following
      elective ND.A further two trials compared elective radical ND with elective
      selective ND and found no difference in overall survival, disease free survival
      or recurrence. The final trial compared surgery plus radiotherapy to radiotherapy
      alone but data were unreliable because the trial stopped early and there were
      multiple protocol violations.None of the trials reported quality of life as an
      outcome. Two trials, evaluating different comparisons reported adverse effects of
      treatment. AUTHORS' CONCLUSIONS: Seven included trials evaluated neck dissection
      surgery in patients with oral cavity cancers. The review found weak evidence that
      elective neck dissection of clinically negative neck nodes at the time of removal
      of the primary tumour results in reduced locoregional recurrence, but there is
      insufficient evidence to conclude that elective neck dissection increases overall
      survival or disease free survival compared to therapeutic neck dissection. There
      is very weak evidence from one trial that elective supraomohyoid neck dissection
      may be associated with increased overall and disease free survival. There is no
      evidence that radical neck dissection increases overall survival compared to
      conservative neck dissection surgery. Reporting of adverse events in all trials
      was poor and it was not possible to compare the quality of life of patients
      undergoing different surgeries.

PMID- 21901704
TI  - Managerial supervision to improve primary health care in low- and middle-income
      countries.
AB  - BACKGROUND: Primary healthcare (PHC) workers often work alone or in isolation.
      Healthcare managerial supervision is recommended to help assure quality; but this
      requires skilled supervisors and takes time and resources. It is therefore
      important to assess to what extent supervision is beneficial and the ways in
      which it can be implemented. OBJECTIVES: To review the effects of managerial
      supervision of health workers to improve the quality of PHC (such as adherence to
      guidance or coverage of services) in low- and middle-income countries. SEARCH
      STRATEGY: We searched The Cochrane Central Register of Controlled Trials
      (CENTRAL) 2011, Issue 1, part of The Cochrane Library.
      www.thecochranelibrary.com, including the Cochrane Effective Practice and
      Organisation of Care (EPOC) Group Specialised Register (searched 10 March 2011);
      MEDLINE, Ovid 1950 to March Week 1 2011 (searched 08 March 2011); EMBASE, Ovid
      1980 to 2011 Week 12 (searched 08 March 2011); CINAHL, Ebsco 1981 - present
      (searched 10 March 2011); LILACS, VHL (searched 10 March 2011). SELECTION
      CRITERIA: Randomised controlled trials, controlled before-and-after studies, and
      interrupted time series studies, conducted in PHC in low- and middle-income
      countries. Supervision includes site visits from a central level of the health
      system, plus at least one supervisory activity. We excluded studies aimed solely
      at improving the clinical skills of PHC workers. DATA COLLECTION AND ANALYSIS: We
      extracted data using a predefined form and assessed for risk of bias using the
      EPOC risk of bias criteria. Data are presented in a narrative way without pooling
      the effects on the outcomes as studies and outcomes were diverse. MAIN RESULTS:
      Nine studies met the inclusion criteria: three compared supervision with no
      supervision, five compared enhanced supervision with routine supervision, and one
      study compared less intensive supervision with routine supervision. Most outcomes
      were scores relating to providers' practice, knowledge and provider or user
      satisfaction. The majority of the outcomes were measured within nine months after
      the interventions were introduced. In two studies comparing supervision with no
      supervision, small benefits on provider practice and knowledge were found. For
      methods of enhancing supervision, we identified five studies, and two studies of
      frequent supportive supervision demonstrated small benefits on workers
      performance. The one study examining the impact of less intensive supervision
      found no evidence that reducing the frequency of visits had any effect on the
      utilisation of services. The GRADE evidence quality for all comparisons and
      outcomes was "low" or "very low". AUTHORS' CONCLUSIONS: It is uncertain whether
      supervision has a substantive, positive effect on the quality of primary health
      care in low- and middle-income countries. The long term effectiveness of
      supervision is unknown.

PMID- 21901705
TI  - Specialised antenatal clinics for women with a pregnancy at high risk of preterm
      birth (excluding multiple pregnancy) to improve maternal and infant outcomes.
AB  - BACKGROUND: Amongst the risk factors for preterm birth, previous preterm delivery
      is a strong predictor. Specialised clinics for women with a history of
      spontaneous preterm delivery have been advocated as a way of improving outcomes
      for women and their infants. OBJECTIVES: To assess using the best available
      evidence, the value of specialised antenatal clinics for women with a pregnancy
      at high risk of preterm delivery when compared with 'standard' antenatal clinics.
      SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials
      Register (30 June 2011). SELECTION CRITERIA: All published, unpublished, and
      ongoing randomised controlled trials (including cluster-randomised trials)
      examining specialised compared with standard antenatal clinic care for women with
      a singleton pregnancy considered at high risk of preterm labour. DATA COLLECTION
      AND ANALYSIS: Two review authors independently assessed trial quality and
      extracted data. MAIN RESULTS: We included three trials with 3400 women, all
      carried out in the USA. All focused on specialised clinics for women at high risk
      of preterm birth. Gestational age at delivery, preterm delivery, or both were
      primary outcomes in all studies. The interventions in the three trials
      differed.Overall there was very little data on our prespecified outcomes. For
      most outcomes a single study provided data, hence there was not the statistical
      power to detect any possible differences between groups. There was no clear
      evidence that specialised antenatal clinics reduce the number of preterm births.
      AUTHORS' CONCLUSIONS: Specialised antenatal clinics are now an accepted part of
      care in many settings, and carrying out further randomised trials may not be
      possible. Any future research in this area should include psychological outcomes
      and should focus on which aspects of service provision are preferred by women.
      Such research could underpin further service development in this area.

PMID- 21901706
TI  - Probiotics for preventing acute upper respiratory tract infections.
AB  - BACKGROUND: Probiotics may improve a person's health by regulating their immune
      function. Some studies show that probiotic strains can prevent respiratory
      infections. However, no evidence of the benefits of probiotics for acute upper
      respiratory tract infections (URTIs) and related potential adverse effects has
      been published. OBJECTIVES: To assess the effectiveness and safety of probiotics
      for preventing acute URTIs. SEARCH STRATEGY: We searched the Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 2),
      which includes the Cochrane Acute Respiratory Infections Group's Specialised
      Register, MEDLINE (Ovid) (1950 to May week 1, 2011), EMBASE (1974 to May 2011),
      Web of Science which includes Science Citation Index (from 1900 to May 2011) and
      Conference Proceedings Citation Index (from 1991 to May 2011), the Chinese
      Biomedical Literature Database, which includes the China Biological Medicine
      Database (from 1978 to May 2011), the Chinese Medicine Popular Science Literature
      Database (from 2000 to May 2011) and the Masters Degree Dissertation of Beijing
      Union Medical College Database (from 1981 to May 2011). SELECTION CRITERIA:
      Randomised controlled trials (RCTs) comparing probiotics with placebo to prevent
      acute URTIs. DATA COLLECTION AND ANALYSIS: Two review authors independently
      assessed eligibility, quality of trials and extracted data. MAIN RESULTS: We
      included 14 RCTs, although we could only extract available data to meta-analyse
      in 10 trials which involved 3451 participants. We found that probiotics were
      better than placebo when measuring the number of participants experiencing
      episodes of acute URTI: at least one episode: odds ratio (OR) 0.58; 95%
      confidence interval (CI) 0.36 to 0.92; at least three episodes: OR 0.53; 95% CI
      0.36 to 0.80; rate ratio of episodes of acute URTI: rate ratio 0.88; 95% CI 0.81
      to 0.96; and reduced antibiotic prescription rates for acute URTIs: OR 0.67; 95%
      CI 0.45 to 0.98. Probiotics and placebo were similar when measuring the mean
      duration (MD) of an episode of acute URTI: MD -0.29; 95% CI -3.71 to 3.13 and
      adverse events: OR 0.92; 95% CI 0.37 to 2.28. Side effects of probiotics were
      minor and gastrointestinal symptoms were the most common. We found that some
      subgroups had a high level of heterogeneity when conducting pooled analyses.
      AUTHORS' CONCLUSIONS: Probiotics were better than placebo in reducing the number
      of participants experiencing episodes of acute URTIs, the rate ratio of episodes
      of acute URTI and reducing antibiotic use. This indicates that probiotics may be
      more beneficial than placebo for preventing acute URTIs. However, the results
      have some limitations and there were no data for older people.

PMID- 21901707
TI  - Neurosurgical interventions for the treatment of classical trigeminal neuralgia.
AB  - BACKGROUND: Surgical interventions are used for trigeminal neuralgia when drug
      treatment fails. Surgical treatments divide into two main categories, ablative
      (destructive) or non-ablative. These treatments can be done at three different
      sites: peripherally, at the Gasserian ganglion level, and within the posterior
      fossa of the skull. OBJECTIVES: To assess the efficacy of neurosurgical
      interventions for classical trigeminal neuralgia in terms of pain relief, quality
      of life and any harms. To determine if there are defined subgroups of patients
      more likely to benefit. SEARCH STRATEGY: We searched the Cochrane Neuromuscular
      Disease Group Specialized Register, (13 May 2010), CENTRAL (issue 2, 2010 part of
      the Cochrane Library), Health Technology Assessment (HTA) Database, NHS Economic
      Evaluation Database (NHSEED) and Database of Abstracts of Reviews of Effects
      (DARE) (issue 4, 2010 (HTA, NHSEED and DARE are part of the Cochrane Library)),
      MEDLINE (January 1966 to May 2010) and EMBASE (January 1980 to May 2010) with no
      language exclusion. SELECTION CRITERIA: Randomised controlled trials and quasi
      randomised controlled trials of neurosurgical interventions used in the treatment
      of classical trigeminal neuralgia. DATA COLLECTION AND ANALYSIS: Two authors
      independently assessed trial quality and extracted data. We contacted authors for
      clarification and missing information whenever possible. MAIN RESULTS: Eleven
      studies involving 496 participants met some of the inclusion criteria stated in
      the protocol. One hundred and eighty patients in five studies had peripheral
      interventions, 229 patients in five studies had percutaneous interventions
      applied to the Gasserian ganglion, and 87 patients in one study underwent two
      modalities of stereotactic radiosurgery (Gamma Knife) treatment. No studies
      addressing microvascular decompression (which is the only non-ablative procedure)
      met the inclusion criteria. All but two of the identified studies had a high to
      medium risk of bias because of either missing data or methodological
      inconsistency. It was not possible to undertake meta-analysis because of
      differences in the intervention modalities and variable outcome measures. Three
      studies had sufficient outcome data for analysis. One trial, which involved 40
      participants, compared two techniques of radiofrequency thermocoagulation (RFT)
      of the Gasserian ganglion at six months. Pulsed RFT resulted in return of pain in
      all participants by three months. When this group were converted to conventional
      (continuous) treatment these participants achieved pain control comparable to the
      group that had received conventional treatment from the outset. Sensory changes
      were common in the continuous treatment group. In another trial, of 87
      participants, investigators compared radiation treatment to the trigeminal nerve
      at one or two isocentres in the posterior fossa. There were insufficient data to
      determine if one technique was superior to another. Two isocentres increased the
      incidence of sensory loss. Increased age and prior surgery were predictors for
      poorer pain relief. Relapses were nonsignificantly reduced with two isocentres
      (risk ratio (RR) 0.72, 95% confidence intervaI (CI) 0.30 to 1.71). A third study
      compared two techniques for RFT in 54 participants for 10 to 54 months. Both
      techniques produced pain relief (not significantly in favour of neuronavigation
      (RR 0.70, 95% CI 0.46 to 1.04) but relief was more sustained and side effects
      fewer if a neuronavigation system was used. The remaining eight studies did not
      report outcomes as predetermined in our protocol. AUTHORS' CONCLUSIONS: There is
      very low quality evidence for the efficacy of most neurosurgical procedures for
      trigeminal neuralgia because of the poor quality of the trials. All procedures
      produced variable pain relief, but many resulted in sensory side effects. There
      were no studies of microvascular decompression which observational data suggests
      gives the longest pain relief. There is little evidence to help comparative
      decision making about the best surgical procedure. Well designed studies are
      urgently needed.

PMID- 21901708
TI  - Local anaesthetic eye drops for prevention of pain in preterm infants undergoing
      screening for retinopathy of prematurity.
AB  - BACKGROUND: Screening examinations for retinopathy of prematurity (ROP) are
      performed routinely in the neonatal intensive care unit and are a recognised
      cause of pain in the newborn. OBJECTIVES: To determine the effect of instillation
      of topical anaesthetic eye drops compared with placebo or no treatment on pain in
      infants undergoing ROP screening. SEARCH STRATEGY: We used the standard search
      strategy of the Cochrane Neonatal Review Group. This included a search of the
      Cochrane Neonatal Group register and the Cochrane Central Register of Controlled
      Trials (CENTRAL, The Cochrane Library, Issue 10, 2010). We identified relevant
      studies by searching the following: (1) computerised bibliographic databases:
      MEDLINE (1966 to October 2010), EMBASE (1988 to October 2010) and Web of Science
      (1975 to March 2010; (2) the Oxford Database of Perinatal Trials. We searched
      electronically abstracts from PAS from 2000 to 2010 and handsearched abstracts
      from ESPR from 2000 to 2009. SELECTION CRITERIA: All randomised, or quasi
      randomised controlled trials, or randomised cross-over trials. DATA COLLECTION
      AND ANALYSIS: We used the standard methods of the Cochrane Neonatal Review Group.
      MAIN RESULTS: We identified two studies for inclusion. Both studies were
      randomised cross-over trials performed in single centres. Both studies used the
      Premature Infant Pain Profile (PIPP) score as a measure of pain response.
      Different methods of evaluating PIPP scores are presented including the absolute
      PIPP score, a PIPP score > 10 or > 12 and an increase in PIPP >= 4 from the
      baseline value. There is a nonsignificant reduction in pain scores at one minute
      and a nonsignificant increase at five minutes post insertion of the speculum.
      PIPP score > 12 at one minute resulted in a statistically significant reduction
      in the number of patients who experienced pain (typical risk ratio (RR) 0.56, 95%
      CI 0.36 to 0.89; typical risk difference (RD) -0.23, 95% CI -0.39 to -0.86;
      number needed to treat to benefit (NNTB) 4). When pain was defined as an increase
      in PIPP > 4 there was a statistically significant reduction in the absolute
      number of patients who experienced pain at one minute (typical RR 0.70, 95% CI
      0.52 to 0.94; typical RD -0.19, 95% CI -0.34 to -0.04; NNTB 5.3). AUTHORS'
      CONCLUSIONS: The administration of topical proparacaine 30 seconds prior to the
      ophthalmological evaluation was associated with a reduction in pain scores
      especially at the time of speculum insertion. However, despite treatment,
      screening remains a painful procedure and the role of nonpharmacological and
      pharmacological intervention including different local anaesthetic agents should
      be ascertained in future randomised trials.

PMID- 21901709
TI  - Interventions to reduce emigration of health care professionals from low- and
      middle-income countries.
AB  - BACKGROUND: The emigration of skilled professionals from low- and middle-income
      countries (LMICs) to high-income countries (HICs) is a general phenomenon but
      poses particular challenges in health care, where it contributes to human
      resource shortages in the health systems of poorer countries. However, little is
      known about the effects of strategies to help regulate this movement. OBJECTIVES:
      To assess the effects of policy interventions to regulate emigration of health
      professionals from LMICs. SEARCH STRATEGY: We searched the Cochrane Effective
      Practice and Organisation of Care (EPOC) Group Specialised Register (searched 15
      March 2011), the Cochrane Register of Controlled Trials (CENTRAL) (searched 2
      March 2011), MEDLINE (searched 5 March 2011), EMBASE (searched 2 March 2011),
      CINAHL (searched 5 March 2011), LILACS (searched 7 March 2011), WHOLIS (searched
      20 March 2011), SocINDEX (searched 11 March 2011), EconLit (searched 8 March
      2011), Science and Social Science Citation Index (searched 8 March 2011), NLM
      Gateway (searched 31 March 2011) and ERIC (searched March 3 2011). We reviewed
      reference lists of included studies and selected reviews on the topic, contacted
      authors of included studies and experts on the field, and reviewed relevant
      websites. SELECTION CRITERIA: Randomised controlled trials (RCT), non-randomised
      controlled trials (NRCT), controlled before-and-after studies (CBA) and
      interrupted time series (ITS) studies assessing any intervention in the source,
      the recipient or both countries that could have an impact on the number of
      professionals that emigrate from a LMIC. Health professionals, such as
      physicians, dentists, nurses or midwives, should be nationals of a LMIC whose
      graduate training was in a LMIC. DATA COLLECTION AND ANALYSIS: One review author
      extracted data onto a standard form and a second review author checked data. Two
      review authors assessed risk of bias. MAIN RESULTS: Only one study was included.
      This time series study assessed the migration of Philippine nurses to the United
      States of America (USA) from 1954 to 1990. We re-analysed it as an interrupted
      time series study. The intervention was a modification of migratory law in the
      US, called the 'Act of October 1965', which decreased the restrictions on Eastern
      hemisphere immigrants to the USA. The analysis showed a significant immediate
      increase of 807.6 (95% confidence interval (CI) 480.9 to 1134.3) in the number of
      nurses migrating to the USA annually after the intervention. This represents a
      relative increase of 5000% over the underlying pre-intervention trend. There were
      no significant differences in the slopes of the underlying trends for the number
      of nurses migrating between the pre- and postintervention periods. AUTHORS'
      CONCLUSIONS: There is an important gap in knowledge about the effectiveness of
      policy interventions in either HICs or LMICs that could regulate positively the
      movement of health professionals from LMICs. The only evidence found was from an
      intervention in a HIC that increased the movement of health professionals from a
      LMIC.New initiatives to improve records on the migration of health professionals
      from LMICs should be implemented, as a prerequisite to conducting more rigorous
      research in the field. This research should focus on whether the range of
      interventions outlined in the literature could be effective in retaining health
      professionals in LMICs. Such interventions include financial rewards, career
      development and continuing education, improving hospital infrastructure, resource
      availability, better hospital management and improved recognition of health
      professionals.

PMID- 21901710
TI  - Acupuncture for slowing the progression of myopia in children and adolescents.
AB  - BACKGROUND: Myopia (near-sightedness or short-sightedness) is one of the three
      commonly detected refractive (focusing) errors. Acupuncture is the stimulation of
      acupuncture points by various methods including needle insertion and acupressure.
      It is often used by traditional Chinese medicine practitioners to treat myopia in
      children. OBJECTIVES: To assess the effectiveness and safety of acupuncture in
      slowing the progression of myopia in children and adolescents. SEARCH STRATEGY:
      We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials
      Register) (The Cochrane Library 2011, Issue 7), MEDLINE (January 1950 to July
      2011), EMBASE (January 1980 to July 2011), the Allied and Complementary Medicine
      Database (AMED) (January 1985 to July 2011), Latin American and Caribbean Health
      Sciences Literature Database (LILACS) (January 1982 to July 2011), the
      metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com),
      ClinicalTrials.gov (www.clinicaltrial.gov), the National Center for Complementary
      and Alternative Medicine (NCCAM) (The first issue to August 2010), the Chinese
      Biological Medicine Database (CBM) (1978 to April 2011), China National Knowledge
      Infrastructure (CNKI) (1994 to April 2011) and VIP (1989 to April 2011). There
      were no date or language restrictions in the electronic searches for trials.
      CENTRAL, MEDLINE, EMBASE, AMED, LILACS, mRCT and ClinicalTrials.gov were last
      searched on 9 July 2011. NCCAM was searched up to August 2010 and CBM, CNKI, and
      VIP were last searched on 6 April 2011. SELECTION CRITERIA: We included
      randomized controlled trials (RCTs) that included any type of acupuncture
      treatment for myopia in children and adolescents. DATA COLLECTION AND ANALYSIS:
      Two authors independently evaluated the search results according to the inclusion
      and exclusion criteria. Two authors extracted and assessed data independently. We
      contacted the study investigator for missing data. MAIN RESULTS: We included two
      RCTs conducted in Taiwan with a total of 131 participants. We did not perform a
      meta-analysis as the trials were assessing different outcomes. Neither trial met
      our pre-defined primary outcome criteria of myopia progression defined as one
      diopter mean change. Only one trial reported the changes of axial length without
      non-significant difference among groups and both trials reported that several
      children experienced mild pain during acupuncture stimulation. AUTHORS'
      CONCLUSIONS: Two trials are included in this review but no conclusions can be
      drawn for the benefit of co-acupressure for slowing progress of myopia in
      children. Further evidence in the form of RCTs are needed before any
      recommendations can be made for the use of acupuncture treatment in clinical use.
      These trials should compare acupuncture to placebo and have large sample sizes.
      Other types of acupuncture (such as auricular acupuncture) should be explored
      further as well as compliance with treatment for at least six months or longer.
      Axial length elongation of the eye should be investigated for at least one year.
      The potential to reduce/eliminate pain from acupuncture experienced by children
      should also be reviewed.

PMID- 21901711
TI  - Behavioral interventions to promote condom use among women living with HIV.
AB  - BACKGROUND: High rates of HIV infection among women of reproductive age have
      dramatic consequences for personal and public health. Prophylaxis during sexual
      intercourse in the form of condoms has been the most effective way to prevent
      both STI and HIV transmission among people living with HIV. OBJECTIVES: To
      investigate the effectiveness of behavioral interventions in promoting condom use
      among women living with HIV. SEARCH STRATEGY: We conducted a comprehensive
      literature search in several scientific databases, clinical trials databases,
      conference proceedings, and conference websites to identify studies produced
      between 1980 and May 2010 that met our selection criteria. SELECTION CRITERIA:
      Studies were included in the analysis if they conducted a randomized controlled
      trial that examined the effects of behavioral interventions on condom use among
      HIV-positive women; considered at least one HIV-related behavioral outcome (e.g.,
      reported protected anal, vaginal, or oral sex) or biological outcome (e.g.,
      acquisition of STIs); and one follow-up assessment three months or more after the
      intervention. Studies were assessed irregardless of langauge or publication
      status. DATA COLLECTION AND ANALYSIS: We used random effects models to summarize
      odds ratios (ORs) that compared intervention and control groups with respect to a
      dichotomous outcome (consistent versus inconsistent condom use). We used funnel
      plots to examine publication bias and a chi(2) statistic to test for
      heterogeneity. The methodological and evidence quality was evaluated through risk
      of bias criteria and the GRADE system, respectively. MAIN RESULTS: Five primary
      studies that collectively researched a total of 725 women living with HIV were
      analysed. When compared to standard care or minimal HIV support intervention,
      meta-analysis showed that behavioral interventions had no effect on increasing
      condom use among HIV-positive women. This finding was consistent at various
      follow-up meetings (3, 6, and 12-months) as well as over the entire 12-month
      follow-up period (OR= 0.82; 95% CI 0.65-1.04; p=0.11). Only one study presented
      adequate data to analyze the relationship between behavioral interventions and
      STI incidence. Studies included in this analysis demonstrated low risk of bias
      based on the risk of bias criteria. However, sample size was considered
      inadequate across all studies. AUTHORS' CONCLUSIONS: Meta-analysis shows that
      behavioral interventions have little effect on increasing condom use among HIV
      positive women. However, these findings should be used with caution since results
      were based on a few small trials that were targeted specifically towards HIV
      positive women. To decrease sexual transmission of HIV among this population, we
      recommend interventions that combine condom promotion, family planning provision
      and counselling, and efforts to reduce viral loads among HIV-positive women and
      their partners (e.g., HAART treatment provision). New research is needed to
      address the needs of HIV-positive women, including an assessment of the impact of
      interventions that combine safer sexual behavior and harm reduction approaches.

PMID- 21901712
TI  - Acupuncture for autism spectrum disorders (ASD).
AB  - BACKGROUND: Autism spectrum disorders (ASD) are characterized by impairment in
      social interaction, impairment in communication and lack of flexibility of
      thought and behavior. Acupuncture, which involves the use of needles or pressure
      to specific points on the body, is used widely in Traditional Chinese Medicine
      and increasingly within a western medical paradigm. It has sometimes been used as
      a treatment aimed at improving ASD symptoms and outcomes, but its clinical
      effectiveness and safety has not been rigorously reviewed. OBJECTIVES: To
      determine the effectiveness of acupuncture for people with ASD in improving core
      autistic features, as well as communication, cognition, overall functioning and
      quality of life, and to establish if it has any adverse effects. SEARCH STRATEGY:
      We searched the following databases on 30 September 2010: CENTRAL (The Cochrane
      Library, 2010, Issue 3), MEDLINE (1950 to September 2010 Week 2), EMBASE (1980 to
      2010 Week 38), PsycINFO, CINAHL, China Journal Full-text Database, China Master
      Theses Full-text Database, China Doctor Dissertation Full-text Database, China
      Proceedings of Conference Database, Index to Taiwan Periodical Literature System,
      metaRegister of Controlled Trials and the Chinese Clinical Trials Registry. We
      also searched AMED (26 February 2009) and Dissertation Abstracts International (3
      March 2009), but these were no longer available to the authors or editorial base
      at the date of the most recent search. TCMLARS (Traditional Chinese Medical
      Literature Analysis and Retrieval System) was last searched on 3 March 2009.
      SELECTION CRITERIA: We included randomized and quasi-randomized controlled
      trials. We included studies comparing an acupuncture group with at least one
      control group that used no treatment, placebo or sham acupuncture treatment in
      people with ASD. We excluded trials that compared different forms of acupuncture
      or compared acupuncture with another treatment. DATA COLLECTION AND ANALYSIS: Two
      review authors independently extracted trial data and assessed the risk of bias
      in the trials. We used relative risk (RR) for dichotomous data and mean
      difference (MD) for continuous data. MAIN RESULTS: We included 10 trials that
      involved 390 children with ASD. The age range was three to 18 years and the
      treatment duration ranged from four weeks to nine months. The studies were
      carried out in Hong Kong, mainland China and Egypt.Two trials compared needle
      acupuncture with sham acupuncture and found no difference in the primary outcome
      of core autistic features (RFRLRS total score: MD 0.09; 95% CI -0.03 to 0.21, P =
      0.16), although results suggested needle acupuncture might be associated with
      improvement in some aspects of the secondary outcomes of communication and
      linguistic ability, cognitive function and global functioning.Six trials compared
      needle acupuncture plus conventional treatment with conventional treatment alone.
      The trials used different primary outcome measures and most could not demonstrate
      effectiveness of acupuncture in improving core autistic features in general,
      though one trial reported patients in the acupuncture group were more likely to
      have improvement on the Autism Behavior Checklist (RR 1.53; 95% CI 1.09 to 2.16,
      P = 0.02) and had slightly better post-treatment total scores (MD -5.53; 95% CI 
      10.76 to -0.31, P = 0.04). There was no evidence that acupuncture was effective
      for the secondary outcome of communication and linguistic ability, though there
      seemed to be some benefit for the secondary outcomes of cognitive function and
      global functioning.Two trials compared acupressure plus conventional treatment
      with conventional treatment alone and did not report on the primary outcome.
      Individual study results suggested there may be some benefit from acupressure for
      certain aspects of the secondary outcomes of communication and linguistic
      ability, cognitive function and global functioning.Four trials reported some
      adverse effects, though there was little quantitative information, and at times
      both intervention and control groups experienced them. Adverse effects noted
      included bleeding, crying due to fear or pain, irritability, sleep disturbance
      and increased hyperactivity. None of the trials reported on quality of life.There
      are a number of problems with the evidence base: the trials were few in number
      and included only children; six of the trials were at high risk of bias; they
      were heterogeneous in terms of participants and intervention; they were of short
      duration and follow-up; they reported inconsistent and imprecise results, and,
      due to carrying out large numbers of analyses, they were at risk of false
      positivity. AUTHORS' CONCLUSIONS: Current evidence does not support the use of
      acupuncture for treatment of ASD. There is no conclusive evidence that
      acupuncture is effective for treatment of ASD in children and no RCTs have been
      carried out with adults. Further high quality trials of larger size and longer
      follow-up are needed.

PMID- 21901713
TI  - Acupuncture for pain in endometriosis.
AB  - BACKGROUND: Endometriosis is a prevalent gynaecological condition, significantly
      affecting women's lives. Clinical presentations may vary from absence of symptoms
      to complaints of chronic pelvic pain, most notably dysmenorrhoea. The management
      of pain in endometriosis is currently inadequate. Acupuncture has been studied in
      gynaecological disorders but its effectiveness for pain in endometriosis is
      uncertain. OBJECTIVES: To determine the effectiveness and safety of acupuncture
      for pain in endometriosis.  SEARCH STRATEGY: We searched the Cochrane Menstrual
      Disorders and Subfertility Group (MSDG) Specialised Register of controlled
      trials, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library), MEDLINE, EMBASE, CINAHL, AMED, PsycINFO, CNKI and TCMDS (from inception
      to 2010) and reference lists of retrieved articles. SELECTION CRITERIA:
      Randomised single or double-blind controlled trials enrolling women of
      reproductive age with a laparoscopically confirmed diagnosis of endometriosis and
      comparing acupuncture (body, scalp or auricular) to either placebo or sham, no
      treatment, conventional therapies or Chinese herbal medicine. DATA COLLECTION AND
      ANALYSIS: Three authors independently assessed risk of bias and extracted data;
      we contacted study authors for additional information. Meta-analyses were not
      performed as only one study was included. The primary outcome measure was
      decrease in pain from endometriosis. Secondary outcome measures included
      improvement in quality of life scores, pregnancy rate, adverse effects and rate
      of endometriosis recurrence. MAIN RESULTS: Twenty-four studies were identified
      that involved acupuncture for endometriosis; however only one trial, enrolling 67
      participants, met all the inclusion criteria. The single included trial defined
      pain scores and cure rates according to the Guideline for Clinical Research on
      New Chinese Medicine. Dysmenorrhoea scores were lower in the acupuncture group
      (mean difference -4.81 points, 95% confidence interval -6.25 to -3.37, P <
      0.00001) using the 15-point Guideline for Clinical Research on New Chinese
      Medicine for Treatment of Pelvic Endometriosis scale. The total effective rate
      ('cured', 'significantly effective' or 'effective') for auricular acupuncture and
      Chinese herbal medicine was 91.9% and 60%, respectively (risk ratio 3.04, 95%
      confidence interval 1.65 to 5.62, P = 0.0004). The improvement rate did not
      differ significantly between auricular acupuncture and Chinese herbal medicine
      for cases of mild to moderate dysmenorrhoea, whereas auricular acupuncture did
      significantly reduce pain in cases of severe dysmenorrhoea. Data were not
      available for secondary outcomes measures. AUTHORS' CONCLUSIONS: The evidence to
      support the effectiveness of acupuncture for pain in endometriosis is limited,
      based on the results of only a single study that was included in this review.
      This review highlights the necessity for developing future studies that are well
      designed, double-blinded, randomised controlled trials that assess various types
      of acupuncture in comparison to conventional therapies.

PMID- 21901714
TI  - Remediating buildings damaged by dampness and mould for preventing or reducing
      respiratory tract symptoms, infections and asthma.
AB  - BACKGROUND: Dampness and mould in buildings have been associated with adverse
      respiratory symptoms, asthma and respiratory infections of inhabitants. Moisture
      damage is a very common problem in private houses, workplaces and public
      buildings such as schools. OBJECTIVES: To determine the effectiveness of
      remediating buildings damaged by dampness and mould in order to reduce or prevent
      respiratory tract symptoms, infections and symptoms of asthma. SEARCH STRATEGY:
      We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2011, Issue 2), which contains the Cochrane Acute Respiratory
      Infections Group's Specialised Register, MEDLINE (1951 to June week 1, 2011),
      EMBASE (1974 to June 2011), CINAHL (1982 to June 2011), Science Citation Index
      (1973 to June 2011), Biosis Previews (1989 to June 2011), NIOSHTIC (1930 to
      November 2010) and CISDOC (1974 to November 2010). SELECTION CRITERIA: Randomised
      controlled trials (RCTs), cluster-RCTs (cRCTs), interrupted time series studies
      and controlled before-after (CBA) studies of the effects of remediating dampness
      and mould in a building on respiratory symptoms, infections and asthma. DATA
      COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed
      the risk of bias in the included studies. MAIN RESULTS: We included eight studies
      (6538 participants); two RCTs (294 participants), one cRCT (4407 participants)
      and five CBA studies (1837 participants). The interventions varied from thorough
      renovation to cleaning only. We found moderate-quality evidence in adults that
      repairing houses decreased asthma-related symptoms (among others, wheezing (odds
      ratio (OR) 0.64; 95% confidence interval (CI) 0.55 to 0.75) and respiratory
      infections (among others, rhinitis (OR 0.57; 95% CI 0.49 to 0.66)). For children,
      we found moderate-quality evidence that the number of acute care visits (among
      others mean difference (MD) -0.45; 95% CI -0.76 to -0.14)) decreased in the group
      receiving thorough remediation.One CBA study showed very low-quality evidence
      that after repairing a mould-damaged office building, asthma-related and other
      respiratory symptoms decreased. For children and staff in schools, there was very
      low-quality evidence that asthma-related and other respiratory symptoms in mould
      damaged schools were similar to those of children and staff in non-damaged
      schools, both before and after intervention. For children, respiratory infections
      might have decreased after the intervention. AUTHORS' CONCLUSIONS: We found
      moderate to very low-quality evidence that repairing mould-damaged houses and
      offices decreases asthma-related symptoms and respiratory infections compared to
      no intervention in adults. There is very low-quality evidence that although
      repairing schools did not significantly change respiratory symptoms in staff or
      children, pupils' visits to physicians due to a common cold were less frequent
      after remediation of the school. Better research, preferably with a cRCT design
      and with more validated outcome measures, is needed.

PMID- 21901715
TI  - Angiogenesis inhibitors for the treatment of ovarian cancer.
AB  - BACKGROUND: Many women with ovarian cancer eventually develop resistance to
      conventional chemotherapy drugs, and so novel agents are being developed to
      target specific molecular pathways. One such class of drugs inhibits angiogenesis
      (the development of new blood vessels), which is essential for tumour growth. It
      is important to establish whether the addition of these new drugs to conventional
      chemotherapy regimens improves survival, and what the side-effects may be.
      OBJECTIVES: To compare the effectiveness and toxicities of angiogenesis
      inhibitors in the treatment of ovarian cancer. SEARCH STRATEGY: We sought to
      identify completed randomised controlled trials (RCTs) by searching The Cochrane
      Gynaecological Cancer Review Group's Trial Register, The Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10),
      MEDLINE and EMBASE (1990 to October 2010). We also searched registers of clinical
      trials, and contacted investigators of completed and ongoing trials for further
      information. SELECTION CRITERIA: Randomised controlled studies comparing
      angiogenesis inhibitors with either standard chemotherapy or no treatment, in
      women with ovarian cancer. DATA COLLECTION AND ANALYSIS: Two independent authors
      carried out data collection and extraction. We used a random-effects model for
      pooling data. MAIN RESULTS: We did not find any fully-published, completed RCTs
      of angiogenesis inhibitors that met our inclusion criteria. We identified five
      abstracts of completed RCTs of four different angiogenesis-inhibiting agents,
      with a total of 3701 participants.Meta-analysis of two trials found no
      statistically significant difference in overall survival (OS) between women with
      newly-diagnosed advanced ovarian cancer who received concurrent and maintenance
      bevacizumab compared to those who received chemotherapy (carboplatin and
      paclitaxel) alone. However, women who received concurrent and maintenance
      bevacizumab had their risk of disease progression reduced by a quarter (hazard
      ratio (HR) 0.75, 95% confidence interval (CI) 0.68 to 0.83; P < 0.001); they also
      had a significantly increased risk of severe gastrointestinal adverse events,
      moderate or severe hypertension and severe bleeding.One trial also compared
      chemotherapy to concurrent (but not maintenance bevacizumab), and found no
      statistically significant difference in OS or progression-free survival (PFS). 
      However, the women who received bevacizumab had a significantly higher risk of
      moderate or severe hypertension.A three-armed RCT, of paclitaxel alone or with
      low- or high-dose AMG 386, in women with recurrent ovarian cancer, found no
      statistically significant difference in OS. However, women who received low-dose
      AMG 386 had a third less risk of disease progression than those who received
      placebo (HR 0.57, 95% CI 0.36 to 0.91; P = 0.02). The trial found no evidence of
      increased adverse events in the intervention arms.Two relatively small RCTs (one
      of VEGF-Trap, the other of BIBF 1120) found no evidence of either significant
      survival benefit or increased severe adverse events, compared to placebo, but
      they both lacked statistical power. All five trials had unclear risk of bias,
      largely because they have only been published in abstract form, and thus many
      methodological details are unclear. We identified twelve suitable ongoing trials.
      AUTHORS' CONCLUSIONS: There is, as yet, no fully-published RCT evidence for the
      efficacy or safety of angiogenesis inhibitors for the treatment of ovarian
      cancer, but some preliminary results are available from five trials. There is
      some evidence from a meta-analysis of two trials that the addition of concurrent
      and maintenance bevacizumab to standard chemotherapy may reduce the risk of
      disease progression, in women with newly-diagnosed advanced ovarian cancer. There
      is also some evidence from a single trial that low-dose AMG 386 may reduce the
      risk of disease progression in women with recurrent ovarian cancer. However,
      there is currently no evidence that angiogenesis inhibitors improve OS, nor is
      there enough evidence to justify the routine use of angiogenesis inhibitors in
      treating women with ovarian cancer. We eagerly await both the more detailed
      results of these five completed trials, and the preliminary results of the
      several ongoing trials.

PMID- 21901716
TI  - Medical interventions for treating anthracycline-induced symptomatic and
      asymptomatic cardiotoxicity during and after treatment for childhood cancer.
AB  - BACKGROUND: Anthracyclines are frequently used chemotherapeutic agents for
      childhood cancer that can cause cardiotoxicity during and after treatment.
      Although several medical interventions in adults with symptomatic or asymptomatic
      cardiac dysfunction due to other causes are beneficial, it is not known if the
      same treatments are effective for childhood cancer patients and survivors with
      anthracycline-induced cardiotoxicity. OBJECTIVES: To compare the effect of
      medical interventions on anthracycline-induced cardiotoxicity in childhood cancer
      patients or survivors with the effect of placebo, other medical interventions or
      no treatment. SEARCH STRATEGY: We searched the Cochrane Central Register of
      Controlled Trials (CENTRAL) (The Cochrane Library, 2011, issue 1), MEDLINE/PubMed
      (1949 to May 2011) and EMBASE/Ovid (1980 to May 2011) for potentially relevant
      articles. We additionally searched reference lists of relevant articles,
      conference proceedings and ongoing trial databases. SELECTION CRITERIA:
      Randomised controlled trials (RCTs) or controlled clinical trials (CCTs)
      comparing the effectiveness of medical interventions to treat anthracycline
      induced cardiotoxicity with either placebo, other medical interventions or no
      treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently
      performed the study selection. One review author performed the data extraction
      and 'Risk of bias' assessments which were checked by another review author. MAIN
      RESULTS: We identified two RCTs. One trial (135 patients) compared enalapril with
      placebo in childhood cancer survivors with asymptomatic anthracycline induced
      cardiac dysfunction. The other trial (68 patients) compared a two-week treatment
      of phosphocreatine with a control treatment (vitamin C, ATP, vitamin E, oral
      coenzyme Q10) in leukaemia patients with anthracycline-induced cardiotoxicity.
      Both studies had methodological limitations.The RCT on enalapril showed no
      (statistically) significant differences in overall survival, mortality due to
      heart failure, development of clinical heart failure and quality of life between
      treatment and control group. A post-hoc analysis showed a decrease (i.e.
      improvement) in one measure of cardiac function (left ventricular end systolic
      wall stress (LVESWS): -8.62% change) compared with placebo (+1.66% change) in the
      first year of treatment (P = 0.036), but not afterwards. Patients treated with
      enalapril had a higher risk of dizziness or hypotension (RR 7.17, 95% CI 1.71 to
      30.17) and fatigue (Fisher's exact test, P = 0.013).The RCT on phosphocreatine
      found no differences in overall survival, mortality due to heart failure,
      echocardiographic cardiac function and adverse events between treatment and
      control group. AUTHORS' CONCLUSIONS: For the effect of enalapril in childhood
      cancer survivors with asymptomatic cardiac dysfunction, only one RCT is
      available. Although there is some evidence that enalapril temporarily improves
      one parameter of cardiac function (LVESWS), it is unclear whether it improves
      clinical outcomes. Enalapril was associated with a higher risk of dizziness or
      hypotension and fatigue. Clinicians should weigh the possible benefits with the
      known side-effects of enalapril in childhood cancer survivors with asymptomatic
      anthracycline-induced cardiotoxicity.For the effect of phosphocreatine in
      childhood cancer patients with anthracycline-induced cardiotoxicity, only one RCT
      is available. Limited data with a high risk of bias showed no significant
      difference between phosphocreatine and control treatment on echocardiographic
      function and clinical outcomes.We did not identify any RCTs or CCTs studying
      other medical interventions for symptomatic or asymptomatic cardiotoxicity in
      childhood cancer patients or survivors.High-quality studies should be performed.

PMID- 21901717
TI  - Psychological and pharmacological interventions for depression in patients with
      coronary artery disease.
AB  - BACKGROUND: Depression occurs frequently in patients with coronary artery disease
      (CAD) and is associated with a poor prognosis. OBJECTIVES: To determine the
      effects of psychological and pharmacological interventions for depression in CAD
      patients with comorbid depression. SEARCH STRATEGY: CENTRAL, DARE, HTA and EED on
      The Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, ISRCTN Register and
      CardioSource Registry were searched. Reference lists of included randomised
      controlled trials (RCTs) were examined and primary authors contacted. No language
      restrictions were applied. SELECTION CRITERIA: RCTs investigating psychological
      and pharmacological interventions for depression in adults with CAD and comorbid
      depression were included. Primary outcomes were depression, mortality and cardiac
      events. Secondary outcomes were healthcare costs and health-related quality of
      life (QoL). DATA COLLECTION AND ANALYSIS: Two reviewers independently examined
      the identified papers for inclusion and extracted data from included studies.
      Random effects model meta-analyses were performed to compute overall estimates of
      treatment outcomes. MAIN RESULTS: The database search identified 3,253
      references. Sixteen trials fulfilled the inclusion criteria. Psychological
      interventions show a small beneficial effect on depression compared to usual care
      (range of SMD of depression scores across trials and time frames: -0.81;0.12).
      Based on one trial per outcome, no beneficial effects on mortality rates, cardiac
      events, cardiovascular hospitalizations and QoL were found, except for the
      psychosocial dimension of QoL. Furthermore, no differences on treatment outcomes
      were found between the varying psychological approaches. The review provides
      evidence of a small beneficial effect of pharmacological interventions with
      selective serotonin reuptake inhibitors (SSRIs) compared to placebo on depression
      outcomes (pooled SMD of short term depression change scores: -0.24 [-0.38,-0.09];
      pooled OR of short term depression remission: 1.80 [1.18,2.74]). Based on one to
      three trials per outcome, no beneficial effects regarding mortality, cardiac
      events and QoL were found. Hospitalization rates (pooled OR of three trials: 0.58
      [0.39,0.85] and emergency room visits (OR of one trial: 0.58 [0.34,1.00]) were
      reduced in trials of pharmacological interventions compared to placebo. No
      evidence of a superior effect of Paroxetine (SSRI) versus Nortriptyline (TCA)
      regarding depression outcomes was found in one trial. AUTHORS' CONCLUSIONS:
      Psychological interventions and pharmacological interventions with SSRIs may have
      a small yet clinically meaningful effect on depression outcomes in CAD patients.
      No beneficial effects on the reduction of mortality rates and cardiac events were
      found. Overall, however, the evidence is sparse due to the low number of high
      quality trials per outcome and the heterogeneity of examined populations and
      interventions.

PMID- 21901718
TI  - Colony-stimulating factors for prevention and treatment of infectious
      complications in patients with acute myelogenous leukemia.
AB  - BACKGROUND: Acute myelogenous leukemia (AML) is a fatal bone marrow cancer.
      Colony-stimulating factors (CSFs) are frequently administered during and after
      chemotherapy to reduce complications. However, their safety with regard to
      disease-related outcomes and survival in AML is unclear. Therefore, we performed
      a systematic review and meta-analysis to evaluate the impact of CSFs on patient
      outcomes, including survival. OBJECTIVES: To assess the safety/efficacy of CSFs
      with regard to disease-related outcomes and survival in patients with AML. SEARCH
      STRATEGY: We conducted a comprehensive search strategy. We identified relevant
      randomized clinical trials by searching the Cochrane Central Register of
      Controlled Trials (The Cochrane Library 2010, Issue 7), MEDLINE (January 1966 to
      July 2010), LILACS (up to December 2009), databases of ongoing trials and
      relevant conference proceedings. SELECTION CRITERIA: Randomized controlled trials
      that compared the addition of CSFs during and following chemotherapy to
      chemotherapy alone in patients with AML. We excluded trials evaluating the role
      of CSFs administered for the purpose of stem cell collection and/or priming (e.g.
      before and/or only for the duration of chemotherapy). DATA COLLECTION AND
      ANALYSIS: Two review authors appraised the quality of trials and extracted data.
      For each trial, we expressed results as relative risk (RR) with 95% confidence
      intervals (CI) for dichotomous data. We analyzed time-to-event outcomes as hazard
      ratios (HRs). MAIN RESULTS: The search yielded 19 trials including 5256 patients.
      The addition of CSFs to chemotherapy yielded no difference in all-cause mortality
      at 30 days and at the end of follow up (RR 0.97; 95% CI 0.80 to 1.18 and RR 1.01;
      95% CI 0.98 to 1.05, respectively) or in overall survival(HR 1.00; 95% 0.93 to
      1.08). There was no difference in complete remission rates(RR 1.03; 95% CI 0.99
      to 1.07), relapse rates(RR 0.97; 95% CI 0.89 to 1.05) and disease-free
      survival(HR 1.00; 95% CI 0.90 to 1.13). CSFs did not decrease the occurrence of
      bacteremias(RR 0.96; 95% CI 0.82 to 1.12), nor the occurrence of invasive fungal
      infections(RR 1.40; 95% CI 0.90 to 2.19). CSFs marginally increased adverse
      events requiring discontinuation of CSFs as compared to the control arm(RR 1.33;
      95% CI 1.00 to 1.56). AUTHORS' CONCLUSIONS: The addition of CSFs to chemotherapy
      does not adversely influence all-cause mortality, complete remission or relapse
      rates in patients with AML. Although the benefit of CSFs is limited to reduction
      of neutropenic and febrile days, they can be administered safely when necessary.

PMID- 21901719
TI  - Long-term effects of weight-reducing diets in hypertensive patients.
AB  - BACKGROUND: All major guidelines for antihypertensive therapy recommend weight
      loss. Thus dietary interventions that aim to reduce body weight might be a useful
      intervention to reduce blood pressure and adverse cardiovascular events
      associated with hypertension. OBJECTIVES: Primary objectivesTo assess the long
      term effects of weight-reducing diets in hypertensive patients on-   all cause
      mortality -   cardiovascular morbidity -   adverse events (including total
      serious adverse events, withdrawal due to adverse events and total non-serious
      adverse events)Secondary objectivesTo assess the long-term effects of weight
      reducing diets in hypertensive patients on-   change from baseline in systolic
      blood pressure -   change from baseline in diastolic blood pressure -   body
      weight reduction SEARCH STRATEGY: Studies were obtained from computerised
      searches of Ovid MEDLINE, EMBASE, CENTRAL and from searches in reference lists
      and systematic reviews. SELECTION CRITERIA: Randomised controlled trials (RCT) in
      adult hypertensive patients were included if they had a study duration of at
      least 24 weeks and compared weight reducing dietary interventions to no dietary
      intervention in adult patients with primary hypertension. DATA COLLECTION AND
      ANALYSIS: Two authors independently assessed risk of bias and extracted data.
      Studies were pooled using fixed-effect meta-analysis. In case of moderate or
      larger heterogeneity as measured by Higgins I(2), a random effects model was
      used. MAIN RESULTS: Eight studies involving a total of 2100 participants with
      high blood pressure and a mean age of 45 to 66 years met our inclusion criteria.
      Mean treatment duration was 6 to 36 months. No study included mortality as a pre
      defined outcome. One RCT evaluated the effects of dietary weight loss on a
      combined endpoint, consisting of the necessity of reinstating antihypertensive
      therapy and severe cardiovascular complications. In this RCT weight reducing diet
      lowered the endpoint, hazard ratio 0.70 (95% confidence interval [CI], 0.57 to
      0.87) compared to no diet. None of the studies evaluated adverse events as
      designated in our protocol. Blood pressure was reduced in patients assigned to
      weight loss diets as compared to controls: systolic blood pressure (SBP):
      weighted mean difference (WMD): -4.5 mm Hg; 95% CI, -7.2 to -1.8 mm Hg (3 of  8 
      studies included in analysis), and diastolic blood pressure (DBP): WMD -3.2 mm
      Hg; 95% CI, -4.8 to -1.5 mm Hg (3 of  8  studies included in analysis). Patients'
      body weight was also reduced in dietary weight loss groups as compared to
      controls, WMD of -4.0 kg (95% CI: -4.8 to -3.2) (5 of  8  studies included in
      analysis). Two studies used withdrawal of antihypertensive medication as their
      primary outcome. Even though this was not considered a relevant outcome for this
      review, the results of these studies strengthen the finding of reduction of blood
      pressure by dietary weight loss interventions. AUTHORS' CONCLUSIONS: In patients
      with primary hypertension, weight loss diets reduced body weight and blood
      pressure, however the magnitude of the effects are uncertain as a result of the
      small number of patients and studies that could be included in the analyses. It
      is not known whether weight loss reduces mortality and morbidity. No useful
      information on adverse effects was reported in the relevant trials.

PMID- 21901720
TI  - Virtual reality for stroke rehabilitation.
AB  - BACKGROUND: Virtual reality and interactive video gaming have emerged as new
      treatment approaches in stroke rehabilitation. In particular, commercial gaming
      consoles are being rapidly adopted in clinical settings; however, there is
      currently little information about their effectiveness. OBJECTIVES: To evaluate
      the effects of virtual reality and interactive video gaming on upper limb, lower
      limb and global motor function after stroke. SEARCH STRATEGY: We searched the
      Cochrane Stroke Group Trials Register (March 2010), the Cochrane Central Register
      of Controlled Trials (The Cochrane Library 2010, Issue 1), MEDLINE (1950 to March
      2010), EMBASE (1980 to March 2010) and seven additional databases. We also
      searched trials registries, conference proceedings, reference lists and contacted
      key researchers in the area and virtual reality equipment manufacturers.
      SELECTION CRITERIA: Randomised and quasi-randomised trials of virtual reality
      ('an advanced form of human-computer interface that allows the user to 'interact'
      with and become 'immersed' in a computer-generated environment in a naturalistic
      fashion') in adults after stroke. The primary outcomes of interest were: upper
      limb function and activity, gait and balance function and activity and global
      motor function. DATA COLLECTION AND ANALYSIS: Two review authors independently
      selected trials based on pre-defined inclusion criteria, extracted data and
      assessed risk of bias. A third review author moderated disagreements when
      required. The authors contacted all investigators to obtain missing information.
      MAIN RESULTS: We included 19 trials which involved 565 participants. Study sample
      sizes were generally small and interventions and outcome measures varied,
      limiting the ability to which studies could be compared. Intervention approaches
      in the included studies were predominantly designed to improve motor function
      rather than cognitive function or activity performance. The majority of
      participants were relatively young and more than one year post stroke. PRIMARY
      OUTCOMES: results were statistically significant for arm function (standardised
      mean difference (SMD) 0.53, 95% confidence intervals (CI) 0.25 to 0.81 based on
      seven studies with 205 participants). There were no statistically significant
      effects for grip strength or gait speed. We were unable to determine the effect
      on global motor function due to insufficient numbers of comparable studies.
      SECONDARY OUTCOMES: results were statistically significant for activities of
      daily living (ADL) outcome (SMD 0.81, 95% CI 0.39 to 1.22 based on three studies
      with 101 participants); however, we were unable to pool results for cognitive
      function, participation restriction and quality of life or imaging studies. There
      were few adverse events reported across studies and those reported were
      relatively mild. Studies that reported on eligibility rates showed that only 34%
      (standard deviation (SD) 26, range 17 to 80) of participants screened were
      recruited. AUTHORS' CONCLUSIONS: We found limited evidence that the use of
      virtual reality and interactive video gaming may be beneficial in improving arm
      function and ADL function when compared with the same dose of conventional
      therapy. There was insufficient evidence to reach conclusions about the effect of
      virtual reality and interactive video gaming on grip strength or gait speed. It
      is unclear at present which characteristics of virtual reality are most important
      and it is unknown whether effects are sustained in the longer term. Furthermore,
      there are currently very few studies evaluating the use of commercial gaming
      consoles (such as the Nintendo Wii).

PMID- 21901721
TI  - Regular long-term red blood cell transfusions for managing chronic chest
      complications in sickle cell disease.
AB  - BACKGROUND: Sickle cell disease can cause severe vaso-occlusive crises and
      dysfunction of most organ systems. The two most common chronic chest
      complications due to sickle cell disease are pulmonary hypertension and chronic
      sickle lung disease. These complications can lead to morbidity (such as reduced
      exercise tolerance) and increased mortality. OBJECTIVES: The aim of this review
      is to find out whether trials involving people with sickle cell disease that
      compare regular long-term blood transfusion regimens with an alternative
      treatment or no treatment show differences in the following:1. the incidence of
      chronic chest complications (chronic sickle lung disease or pulmonary
      hypertension); 2. the 'severity' or progression of established chronic chest
      complications; 3. the mortality associated with chronic chest complications; and
      4. unacceptable adverse events. SEARCH STRATEGY: We searched the Group's
      Haemoglobinopathies Trials Register. Specific websites were also searched for
      information of ongoing or newly completed trials. The search included the
      reference lists of any randomised controlled trials identified using the above
      methods.Date of the most recent search of the Cochrane Cystic Fibrosis and
      Genetic Disorders Group's Haemoglobinopathies Trials Register: 18 April 2011.
      SELECTION CRITERIA: We included randomized controlled trials. Trials that used
      quasi-randomized methods were to be included if sufficient evidence existed that
      the treatment and control groups were similar at baseline. Trials were eligible
      for inclusion if they investigated regular red blood cell transfusion regimens
      (either simple top-up or exchange transfusions) aimed at reducing the incidence,
      mortality, or objective measures of severity or progression of chronic chest
      complications (chronic sickle lung and pulmonary hypertension) among men or women
      of any age and with one of four common sickle cell disease genotypes, ie Hb SS,
      Sbeta(0), SC, or Sbeta(+). These interventions would be compared to an
      alternative treatment with the same aim or to no treatment. DATA COLLECTION AND
      ANALYSIS: No studies matching the selection criteria were found. MAIN RESULTS: No
      studies matching the selection criteria were found. AUTHORS' CONCLUSIONS: There
      is a need for randomized controlled trials looking at the role of long-term
      transfusion therapy in pulmonary hypertension and chronic sickle lung disease.
      Due to the chronic nature of the conditions, such trials should aim to use a
      combination of objective and subjective measures to assess participants during an
      extended 'steady state' baseline, and after the intervention.

PMID- 21901722
TI  - The effect of financial incentives on the quality of health care provided by
      primary care physicians.
AB  - BACKGROUND: The use of blended payment schemes in primary care, including the use
      of financial incentives to directly reward 'performance' and 'quality' is
      increasing in a number of countries. There are many examples in the US, and the
      Quality and Outcomes Framework (QoF) for general practitioners (GPs) in the UK is
      an example of a major system-wide reform. Despite the popularity of these
      schemes, there is currently little rigorous evidence of their success in
      improving the quality of primary health care, or of whether such an approach is
      cost-effective relative to other ways to improve the quality of care. OBJECTIVES:
      The aim of this review is to examine the effect of changes in the method and
      level of payment on the quality of care provided by primary care physicians
      (PCPs) and to identify:i) the different types of financial incentives that have
      improved quality;ii) the characteristics of patient populations for whom quality
      of care has been improved by financial incentives; andiii) the characteristics of
      PCPs who have responded to financial incentives. SEARCH STRATEGY: We searched the
      Cochrane Effective Practice and Organisation of Care (EPOC) Trials Register,
      Cochrane Central Register of Controlled Trials (CENTRAL) and Cochrane Database of
      Systematic Reviews (CDSR) (The Cochrane Library), MEDLINE, HealthSTAR, EMBASE,
      CINAHL, PsychLIT, and ECONLIT. Searches of Internet-based economics and health
      economics working paper collections were also conducted. Finally, studies were
      identified through the reference lists of retrieved articles, websites of key
      organisations, and from direct contact with key authors in the field. Articles
      were included if they were published from 2000 to August 2009. SELECTION
      CRITERIA: Randomised controlled trials (RCT), controlled before and after studies
      (CBA), and interrupted time series analyses (ITS) evaluating the impact of
      different financial interventions on the quality of care delivered by primary
      healthcare physicians (PCPs). Quality of care was defined as patient reported
      outcome measures, clinical behaviours, and intermediate clinical and
      physiological measures. DATA COLLECTION AND ANALYSIS: Two review authors
      independently extracted data and assessed study quality, in consultation with two
      other review authors where there was disagreement. For each included study, we
      reported the estimated effect sizes and confidence intervals. MAIN RESULTS: Seven
      studies were included in this review. Three of the studies evaluated single
      threshold target payments, one examined a fixed fee per patient achieving a
      specified outcome, one study evaluated payments based on the relative ranking of
      medical groups' performance (tournament-based pay), one study examined a mix of
      tournament-based pay and threshold payments, and one study evaluated changing
      from a blended payments scheme to salaried payment. Three cluster RCTs examined
      smoking cessation; one CBA examined patients' assessment of the quality of care;
      one CBA examined cervical screening, mammography screening, and HbA1c; one ITS
      focused on four outcomes in diabetes; and one controlled ITS (a difference-in
      difference design) examined cervical screening, mammography screening, HbA1c,
      childhood immunisation, chlamydia screening, and appropriate asthma medication.
      Six of the seven studies showed positive but modest effects on quality of care
      for some primary outcome measures, but not all. One study found no effect on
      quality of care. Poor study design led to substantial risk of bias in most
      studies. In particular, none of the studies addressed issues of selection bias as
      a result of the ability of primary care physicians to select into or out of the
      incentive scheme or health plan. AUTHORS' CONCLUSIONS: The use of financial
      incentives to reward PCPs for improving the quality of primary healthcare
      services is growing. However, there is insufficient evidence to support or not
      support the use of financial incentives to improve the quality of primary health
      care. Implementation should proceed with caution and incentive schemes should be
      more carefully designed before implementation. In addition to basing incentive
      design more on theory, there is a large literature discussing experiences with
      these schemes that can be used to draw out a number of lessons that can be
      learned and that could be used to influence or modify the design of incentive
      schemes. More rigorous study designs need to be used to account for the selection
      of physicians into incentive schemes. The use of instrumental variable techniques
      should be considered to assist with the identification of treatment effects in
      the presence of selection bias and other sources of unobserved heterogeneity. In
      randomised trials, care must be taken in using the correct unit of analysis and
      more attention should be paid to blinding. Studies should also examine the
      potential unintended consequences of incentive schemes by having a stronger
      theoretical basis, including a broader range of outcomes, and conducting more
      extensive subgroup analysis. Studies should more consistently describe i) the
      type of payment scheme at baseline or in the control group, ii) how payments to
      medical groups were used and distributed within the groups, and iii) the size of
      the new payments as a percentage of total revenue. Further research comparing the
      relative costs and effects of financial incentives with other behaviour change
      interventions is also required.

PMID- 21901723
TI  - Active case finding in contacts of people with tuberculosis.
AB  - BACKGROUND: Tuberculosis is a major global health challenge that is caused by a
      bacteria which is spread by airborne droplets. Mostly patients are identified in
      high-burden countries when they visit health care facilities ('passive case
      finding'). Contacts of tuberculosis patients are a high-risk group for developing
      the disease. Actively screening contacts of people with confirmed tuberculosis
      may improve case detection rates and control of the disease. OBJECTIVES: This
      study aims to compare whether active case finding among contacts of people with
      confirmed tuberculosis increases case detection compared to usual practice.
      SEARCH STRATEGY: In April 2011 we searched CENTRAL (The Cochrane Library 2011,
      Issue 2), MEDLINE, EMBASE, LILACS and mRCT. We also checked article reference
      lists, the International Journal of Tuberculosis and Lung Disease and contacted
      relevant researchers and organizations. SELECTION CRITERIA: Randomized and quasi
      randomized trials of active case finding to detect tuberculosis disease among
      close and casual contacts of patients with microbiologically proven pulmonary
      tuberculosis (by sputum smear and/or culture). DATA COLLECTION AND ANALYSIS: Two
      authors independently assessed eligibility and the methodological quality of the
      trials that were extracted using a search method that was outlined previously.
      MAIN RESULTS: No trials met the inclusion criteria for this review. One RCT did
      test the effect of active case finding in contacts, but the intervention in that
      trial also included screening for, and treatment of, LTBI in contacts; and the
      separate effect of active case finding could not be estimated. AUTHORS'
      CONCLUSIONS: There are currently insufficient data from randomized controlled
      trials or quasi-randomized controlled trials to evaluate the effect of active
      case finding for tuberculosis among contacts of patients with confirmed disease.
      While observational studies show that contacts have a higher risk of developing
      tuberculosis than the general population, further research is needed to determine
      whether active case finding among contacts significantly increases case detection
      rates.

PMID- 21901724
TI  - Repetitive transcranial magnetic stimulation for the treatment of amyotrophic
      lateral sclerosis or motor neuron disease.
AB  - BACKGROUND: Amyotrophic lateral sclerosis (ALS), also known as motor neuron
      disease (MND), is a progressive neurodegenerative disease without effective
      therapies. Several studies have suggested that repetitive transcranial magnetic
      stimulation (rTMS) may have positive benefit in ALS. However, the efficacy and
      safety of this therapy remain uncertain. OBJECTIVES: We aimed to determine the
      clinical efficacy and safety of rTMS for treating ALS. SEARCH STRATEGY: We
      searched the Cochrane Neuromuscular Disease Group Specialized Register (July
      2010), the Cochrane Central Register of Controlled Trials (The Cochrane Library,
      Issue 2, 2010), MEDLINE (1966 to July 2010), EMBASE (1980 to July 2010), CINAHL
      (1937 to July 2010), Science Citation Index Expanded (January 1945 to June 2010),
      AMED (January 1985 to July 2010) and the Chinese Biomedical Database (1979 to
      September 2010). We also searched for ongoing studies on clinicaltrials.gov
      (September 2010). SELECTION CRITERIA: Randomised and quasi-randomised controlled
      trials assessing the therapeutic efficacy and safety of rTMS for patients with a
      clinical diagnosis of ALS.Comparisons eligible for inclusion were:1. rTMS versus
      no intervention;2. rTMS versus sham rTMS;3. rTMS versus physiotherapy;4. rTMS
      versus medications;5. rTMS + other therapies or drugs versus sham rTMS + the same
      therapies or drugs;6. different methods of application of rTMS such as high
      frequency (> 1Hz) compared to low-frequency (<= 1Hz) rTMS. DATA COLLECTION AND
      ANALYSIS: Two authors independently selected papers, assessed risk of bias and
      extracted data. We resolved disagreements through discussion. We contacted study
      authors for additional information. MAIN RESULTS: Three randomised, placebo
      controlled trials with a total of 50 participants were included in the review.
      All the trials were of poor methodological quality and were insufficiently
      homogeneous to allow the pooling of results. Moreover, the high rate of attrition
      further increased the risk of bias. None of the trials provided detailed data on
      the ALS Functional Rating Scale-Revised (ALSFRS-R) scores at six months follow-up
      which was pre-assigned as our primary outcome. One trial contained data in a
      suitable form for quantitative analysis of our secondary outcomes. No difference
      was seen between rTMS and sham rTMS using the ALSFRS-R scores and manual muscle
      testing (MMT) scores at 12 months follow-up in this trial. Additionally, none of
      the trials reported any adverse events associated with the use of rTMS. However,
      in view of the small sample size, the methodological limitations and incomplete
      outcome data, treatment with rTMS cannot be judged as completely safe. AUTHORS'
      CONCLUSIONS: There is currently insufficient evidence to draw conclusions about
      the efficacy and safety of rTMS in the treatment of ALS. Further studies may be
      helpful if their potential benefit is weighed against the impact of participation
      in a randomised controlled trial on people with ALS.

PMID- 21901725
TI  - Primary closure versus delayed closure for non bite traumatic wounds within 24
      hours post injury.
AB  - BACKGROUND: Acute traumatic wounds are one of the common reasons why people
      present to the emergency department. Primary closure has traditionally been
      reserved for traumatic wounds presenting within six hours of injury and
      considered 'clean' by the attending surgeon, with the rest undergoing delayed
      primary closure as a means of controlling wound infection. Primary closure has
      the potential benefit of rapid wound healing but poses the potential threat of
      increased wound infection. There is currently no evidence to guide clinical
      decision-making on the best timing for closure of traumatic wounds. OBJECTIVES:
      To determine the effect on time to healing of primary closure versus delayed
      closure for non bite traumatic wounds presenting within 24 hours post injury. To
      explore the adverse effects of primary closure compared with delayed closure for
      non bite traumatic wounds presenting within 24 hours post injury. SEARCH
      STRATEGY: We searched the Cochrane Wounds Group Specialised Register (searched 14
      July 2011); the Cochrane Central Register of Controlled Trials (CENTRAL) (The
      Cochrane Library 2011, Issue 3); Ovid MEDLINE (1950 to July Week 1 2011); Ovid
      MEDLINE (In-Process & Other Non-Indexed Citations, July 13, 2011); Ovid EMBASE
      (1980 to 2011 Week 27); and EBSCO CINAHL (1982 to 14 July 2011). There were no
      restrictions with respect to language, date of publication or study setting.
      SELECTION CRITERIA: Randomised controlled trials comparing primary closure with
      delayed closure of non bite traumatic wounds. DATA COLLECTION AND ANALYSIS: Two
      review authors independently evaluated the results of the searches against the
      inclusion criteria. No studies met the inclusion criteria for this review. MAIN
      RESULTS: Since no studies met the inclusion criteria, neither a meta-analysis nor
      a narrative description of studies was possible. AUTHORS' CONCLUSIONS: There is
      currently no systematic evidence to guide clinical decision-making regarding the
      timing for closure of traumatic wounds. There is a need for robust research to
      investigate the effect of primary closure compared with delayed closure for non
      bite traumatic wounds presenting within 24 hours of injury.

PMID- 21901726
TI  - Single dose oral analgesics for acute postoperative pain in adults.
AB  - BACKGROUND: Thirty-five Cochrane Reviews of randomised trials testing the
      analgesic efficacy of individual drug interventions in acute postoperative pain
      have been published. This overview brings together the results of all those
      reviews and assesses the reliability of available data. OBJECTIVES: To summarise
      data from all Cochrane Reviews that have assessed the effects of pharmaceutical
      interventions for acute pain in adults with at least moderate pain following
      surgery, who have been given a single dose of oral analgesic taken alone.
      METHODS: We identified systematic reviews in The Cochrane Library through a
      simple search strategy. All reviews were overseen by a single Review Group, had a
      standard title, and had as their primary outcome numbers of participants with at
      least 50% pain relief over four to six hours compared with placebo. For
      individual reviews we extracted the number needed to treat (NNT) for this outcome
      for each drug/dose combination, and also the percentage of participants achieving
      at least 50% maximum pain relief, the mean of mean or median time to
      remedication, the percentage of participants remedicating by 6, 8, 12, or 24
      hours, and results for participants experiencing at least one adverse event. MAIN
      RESULTS: The overview included 35 separate Cochrane Reviews with 38 analyses of
      single dose oral analgesics tested in acute postoperative pain models, with
      results from about 45,000 participants studied in approximately 350 individual
      studies. The individual reviews included only high-quality trials of standardised
      design and outcome reporting. The reviews used standardised methods and reporting
      for both efficacy and harm. Event rates with placebo were consistent in larger
      data sets. No statistical comparison was undertaken.There were reviews but no
      trial data were available for acemetacin, meloxicam, nabumetone, nefopam,
      sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were
      available for dexibuprofen, dextropropoxyphene 130 mg, diflunisal 125 mg,
      etoricoxib 60 mg, fenbufen, and indometacin. Where there was adequate information
      for drug/dose combinations (at least 200 participants, in at least two studies),
      we defined the addition of four comparisons of typical size (400 participants in
      total) with zero effect as making the result potentially subject to publication
      bias and therefore unreliable. Reliable results were obtained for 46 drug/dose
      combinations in all painful postsurgical conditions; 45 in dental pain and 14 in
      other painful conditions.NNTs varied from about 1.5 to 20 for at least 50%
      maximum pain relief over four to six hours compared with placebo. The proportion
      of participants achieving this level of benefit varied from about 30% to over
      70%, and the time to remedication varied from two hours (placebo) to over 20
      hours in the same pain condition. Participants reporting at least one adverse
      event were few and generally no different between active drug and placebo, with a
      few exceptions, principally for aspirin and opioids.Drug/dose combinations with
      good (low) NNTs were ibuprofen 400 mg (2.5; 95% confidence interval (CI) 2.4 to
      2.6), diclofenac 50 mg (2.7; 95% CI 2.4 to 3.0), etoricoxib 120 mg (1.9; 95% CI
      1.7 to 2.1), codeine 60 mg + paracetamol 1000 mg (2.2; 95% CI 1.8 to 2.9),
      celecoxib 400 mg (2.5; 95% CI 2.2 to 2.9), and naproxen 500/550 mg (2.7; 95% CI
      2.3 to 3.3). Long duration of action (>= 8 hours) was found for etoricoxib 120
      mg, diflunisal 500 mg, oxycodone 10 mg + paracetamol 650 mg, naproxen 500/550 mg,
      and celecoxib 400 mg.Not all participants had good pain relief and for many
      drug/dose combinations 50% or more did not achieve at last 50% maximum pain
      relief over four to six hours. AUTHORS' CONCLUSIONS: There is a wealth of
      reliable evidence on the analgesic efficacy of single dose oral analgesics. There
      is also important information on drugs for which there are no data, inadequate
      data, or where results are unreliable due to susceptibility to publication bias.
      This should inform choices by professionals and consumers.

PMID- 21901727
TI  - Home fortification of foods with multiple micronutrient powders for health and
      nutrition in children under two years of age.
AB  - BACKGROUND: Vitamin and mineral deficiencies, particularly those of iron, vitamin
      A and zinc, affect more than two billion people worldwide. Young children are
      highly vulnerable because of rapid growth and inadequate dietary practices.
      Micronutrient powders (MNP) are single-dose packets containing multiple vitamins
      and minerals in powder form that can be sprinkled onto any semi-solid food.The
      use of MNP for home or point-of-use fortification of complementary foods has been
      proposed as an intervention for improving micronutrient intake in children under
      two years of age. OBJECTIVES: To assess the effects and safety of home (point-of
      use) fortification of foods with multiple micronutrient powders on nutritional,
      health and developmental outcomes in children under two years of age. SEARCH
      STRATEGY: We searched the following databases in February 2011: Cochrane Central
      Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE (1948 to
      week 2 February 2011), EMBASE (1980 to Week 6 2011), CINAHL (1937 to current),
      CPCI-S (1990 to 19 February 2011), Science Citation Index (1970 to 19 February
      2011), African Index Medicus (searched 23 February 2011), POPLINE (searched 21
      February 2011), ClinicalTrials.gov (searched 23 February 2011), mRCT (searched 23
      February 2011), and World Health Organization International Clinical Trials
      Registry Platform (ICTRP) (searched 23 February 2011). We also contacted relevant
      organisations (25 January 2011) for the identification of ongoing and unpublished
      studies. SELECTION CRITERIA: We included randomised and quasi-randomised trials
      with either individual or cluster randomisation. Participants were children under
      the age of two years at the time of intervention, with no specific health
      problems. The intervention was consumption of food fortified at the point of use
      with multiple micronutrient powders formulated with at least iron, zinc and
      vitamin A compared with placebo, no intervention or the use of iron containing
      supplements, which is the standard practice. DATA COLLECTION AND ANALYSIS: Two
      review authors independently assessed the eligibility of studies against the
      inclusion criteria, extracted data from included studies and assessed the risk of
      bias of the included studies. MAIN RESULTS: We included eight trials (3748
      participants) conducted in low income countries in Asia, Africa and the
      Caribbean, where anaemia is a public health problem. The interventions lasted
      between two and 12 months and the powder formulations contained between five and
      15 nutrients. Six trials compared the use of MNP versus no intervention or a
      placebo and the other two compared the use of MNP versus daily iron drops. Most
      of the included trials were assessed as at low risk of bias.Home fortification
      with MNP reduced anaemia by 31% (six trials, RR 0.69; 95% CI 0.60 to 0.78) and
      iron deficiency by 51% (four trials, RR 0.49; 95% CI 0.35 to 0.67) in infants and
      young children when compared with no intervention or placebo, but we did not find
      an effect on growth.In comparison with daily iron supplementation, the use of MNP
      produced similar results on anaemia (one trial, RR 0.89; 95% CI 0.58 to 1.39) and
      haemoglobin concentrations (two trials, MD -2.36 g/L; 95% CI -10.30 to 5.58);
      however, given the limited amount of data these results should be interpreted
      cautiously.No deaths were reported in the trials and information on side effects
      and morbidity, including malaria, was scarce.It seems that the use of MNP is
      efficacious among infants and young children six to 23 months of age living in
      settings with different prevalences of anaemia and malaria endemicity, regardless
      of whether the intervention lasts two, six or 12 months or whether recipients are
      male or female. AUTHORS' CONCLUSIONS: Home fortification of foods with multiple
      micronutrient powders is an effective intervention to reduce anaemia and iron
      deficiency in children six months to 23 months of age. The provision of MNP is
      better than no intervention or placebo and possibly comparable to commonly used
      daily iron supplementation. The benefits of this intervention as a child survival
      strategy or on developmental outcomes are unclear. Data on effects on malaria
      outcomes are lacking and further investigation of morbidity outcomes is needed.
      The micronutrient powders containing multiple nutrients are well accepted but
      adherence is variable and in some cases comparable to that achieved in infants
      and young children receiving standard iron supplements as drops or syrups.

PMID- 21901728
TI  - Transplacental versus direct fetal corticosteroid treatment for accelerating
      fetal lung maturation where there is a risk of preterm birth.
AB  - BACKGROUND: Despite major advances in medical technology, the incidence of
      preterm birth remains high. The use of antenatal corticosteroid administered
      transplacentally, by intramuscular injection to women at risk of preterm birth,
      has reduced the incidence of respiratory distress syndrome and increased the
      survival rates of preterm infants. However, this intervention also comes with its
      own risks and side effects. Animal studies and early studies in pregnant women at
      risk of preterm birth have reported the use of an alternative route of
      administration, by direct intramuscular injection of corticosteroid into the
      fetus under ultrasound guidance, in an attempt to minimise the side effects
      profile. Direct fetal corticosteroid administration may have benefits over
      maternal administration in terms of safety and efficacy. OBJECTIVES: To assess if
      different routes of corticosteroid administration (maternal versus direct fetal)
      have effects on maternal health, and the risk of stillbirth, neonatal, perinatal,
      infant and child mortality and morbidity. SEARCH STRATEGY: We searched the
      Cochrane Pregnancy and Childbirth Group's Trials Register (16 June 2011) and the
      WHO International Clinical Trials Registry Platform (ICTRP) (16 June 2011).
      SELECTION CRITERIA: Randomised controlled trials comparing maternal with direct
      fetal routes of antenatal corticosteroid administration in women at risk of
      preterm birth. DATA COLLECTION AND ANALYSIS: We did not perform any data
      collection or analyses. MAIN RESULTS: We did not identify any eligible randomised
      controlled trials to include in this review. AUTHORS' CONCLUSIONS: The available
      clinical studies carried out so far on animals and human have shown that direct
      intramuscular injection of corticosteroid into the fetus under ultrasound
      guidance is feasible, but data on health outcomes are lacking. Therefore,
      uncertainty persists as to which method could provide better efficacy and safety
      profile. Randomised controlled trials are required focusing on the benefits and
      harms of transplacental versus direct fetal corticosteroid treatment. Until the
      uncertainties have been answered, it is advisable to stay with the current
      standard of antenatal transplacental maternally administered corticosteroid
      treatment.

PMID- 21901729
TI  - The effect of adding inhaled corticosteroids to tiotropium and long-acting
      beta(2)-agonists for chronic obstructive pulmonary disease.
AB  - BACKGROUND: Long-acting bronchodilators comprising long-acting beta(2)-agonists
      and the anticholinergic agent tiotropium are commonly used, either on their own
      or in combination, for managing persistent symptoms of chronic obstructive
      pulmonary disease. Patients with severe chronic obstructive pulmonary disease who
      are symptomatic and who suffer repeated exacerbations are recommended to add
      inhaled corticosteroids to their bronchodilator treatment. However, the benefits
      and risks of adding inhaled corticosteroid to tiotropium and long-acting beta(2)
      agonists for the treatment of chronic obstructive pulmonary disease are unclear.
      OBJECTIVES: To assess the relative effects of adding inhaled corticosteroids to
      tiotropium and long-acting beta(2)-agonists treatment in patients with chronic
      obstructive pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Airways
      Group Specialised Register of trials (February 2011) and reference lists of
      articles. SELECTION CRITERIA: We included parallel group, randomised controlled
      trials of three months or longer comparing inhaled corticosteroid and long-acting
      beta(2)-agonist combination therapy in addition to inhaled tiotropium against
      tiotropium and long-acting beta(2)-agonist treatment for patients with chronic
      obstructive pulmonary disease (COPD). DATA COLLECTION AND ANALYSIS: Two review
      authors independently assessed trials for inclusion and then extracted data on
      trial quality and the outcome results. We contacted study authors for additional
      information. We collected information on adverse effects from the trials. MAIN
      RESULTS: One trial (293 patients) was identified comparing tiotropium in addition
      to inhaled corticosteroid and long-acting beta(2)-agonist combination therapy to
      tiotropium plus long-acting beta(2)-agonist. The study was of good methodological
      quality, however it suffered from high and uneven withdrawal rates between the
      treatment arms. There is currently insufficient evidence to know how much
      difference the addition of inhaled corticosteroids makes to people who are taking
      tiotropium and a long-acting beta(2)-agonist for COPD. AUTHORS' CONCLUSIONS: The
      relative efficacy and safety of adding inhaled corticosteroid to tiotropium and a
      long-acting beta(2)-agonist for chronic obstructive pulmonary disease patients
      remains uncertain and additional trials are required to answer this question.

PMID- 21901730
TI  - Hydrogel dressings for healing diabetic foot ulcers.
AB  - BACKGROUND: Foot ulcers in people with diabetes are a prevalent and serious
      global health issue. Dressings form a key part of ulcer treatment, with
      clinicians and patients having many different types to choose from including
      hydrogel dressings. A clear and current overview of current evidence is required
      to facilitate decision-making regarding dressing use. OBJECTIVES: To assess the
      effects of hydrogel wound dressings compared with alternative dressings or none
      on the healing of foot ulcers in people with diabetes. SEARCH STRATEGY: We
      searched the Cochrane Wounds Group Specialised Register (searched 10 June 2011);
      the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane
      Library 2011, Issue 2); Ovid MEDLINE (1950 to June Week 1 2011); Ovid MEDLINE (In
      Process & Other Non-Indexed Citations, June 8, 2011); Ovid EMBASE (1980 to 2011
      Week 22) and EBSCO CINAHL (1982 to 3 June 2011). There were no restrictions based
      on language or date of publication. SELECTION CRITERIA: Published or unpublished
      randomised controlled trials (RCTs) that have compared the effects on ulcer
      healing of hydrogel with alternative wound dressings or no dressing in the
      treatment of foot ulcers in people with diabetes. DATA COLLECTION AND ANALYSIS:
      Two review authors independently performed study selection, risk of bias
      assessment and data extraction. MAIN RESULTS: We included five studies (446
      participants) in this review. Meta analysis of three studies comparing hydrogel
      dressings with basic wound contract dressings found significantly greater healing
      with hydrogel: risk ratio (RR) 1.80, 95% confidence interval (CI) 1.27 to 2.56.
      The three pooled studies had different follow-up times (12 weeks, 16 weeks and 20
      weeks) and also evaluated ulcers of different severities (grade 3 and 4; grade 2
      and grade unspecified). One study compared a hydrogel dressing with larval
      therapy and found no statistically significant difference in the number of ulcers
      healed and another found no statistically significant difference in healing
      between hydrogel and platelet-derived growth factor. There was also no
      statistically significant difference in number of healed ulcers between two
      different brands of hydrogel dressing. All included studies were small and at
      unclear risk of bias and there was some clinical heterogeneity with studies
      including different ulcer grades. No included studies compared hydrogel with
      other advanced wound dressings. AUTHORS' CONCLUSIONS: There is some evidence to
      suggest that hydrogel dressings are more effective in healing (lower grade)
      diabetic foot ulcers than basic wound contact dressings however this finding is
      uncertain due to risk of bias in the original studies. There is currently no
      research evidence to suggest that hydrogel is more effective than larval therapy
      or platelet-derived growth factors in healing diabetic foot ulcers, nor that one
      brand of hydrogel is more effective than another in ulcer healing. No RCTs
      comparing hydrogel dressings with other advanced dressing types were found.

PMID- 21901731
TI  - Foam dressings for healing diabetic foot ulcers.
AB  - BACKGROUND: Foot ulcers in people with diabetes are a prevalent and serious
      global health issue. Dressings form a key part of ulcer treatment, with
      clinicians and patients having many different types to choose from. A clear and
      current overview of current evidence is required to facilitate decision-making
      regarding dressing use. OBJECTIVES: The review aimed to evaluate the effects of
      foam wound dressings on the healing of foot ulcers in people with diabetes.
      SEARCH STRATEGY: We searched the Cochrane Wounds Group Specialised Register
      (searched 10 June 2011); The Cochrane Central Register of Controlled Trials
      (CENTRAL) (The Cochrane Library 2011, Issue 2); Ovid MEDLINE (1950 to June Week 1
      2011); Ovid MEDLINE (In-Process & Other Non-Indexed Citations, 8 June, 2011);
      Ovid EMBASE (1980 to 2011 Week 22); EBSCO CINAHL (1982 to 3 June 2011). There
      were no restrictions based on language or date of publication. SELECTION
      CRITERIA: Published or unpublished randomised controlled trials (RCTs) that
      evaluated the effects on ulcer healing of one or more foam wound dressings in the
      treatment of foot ulcers in people with diabetes. DATA COLLECTION AND ANALYSIS:
      Two review authors independently performed study selection, risk of bias
      assessment and data extraction. MAIN RESULTS: We included six studies (157
      participants) in this review. Meta analysis of two studies indicated that foam
      dressings do not promote the healing of diabetic foot ulcers compared with basic
      wound contact dressings (RR 2.03, 95%CI 0.91 to 4.55). Pooled data from two
      studies comparing foam and alginate dressing found no statistically significant
      difference in ulcer healing (RR 1.50, 95% CI 0.92 to 2.44). There was no
      statistically significant difference in the number of diabetic foot ulcers healed
      when foam dressings were compared with hydrocolloid (matrix) dressings. All
      included studies were small and/or had limited follow-up times. AUTHORS'
      CONCLUSIONS: Currently there is no research evidence to suggest that foam wound
      dressings are more effective in healing foot ulcers in people with diabetes than
      other types of dressing however all trials in this field are very small. Decision
      makers may wish to consider aspects such as dressing cost and the wound
      management properties offered by each dressing type e.g. exudate management.

PMID- 21901732
TI  - Universal multi-component prevention programs for alcohol misuse in young people.
AB  - BACKGROUND: Alcohol misuse in young people is a cause of concern for health
      services, policy makers, prevention workers, and criminal justice system, youth
      workers, teachers, and parents. OBJECTIVES: To systematically review evidence on
      the effectiveness of universal multi-component prevention programs in preventing
      alcohol misuse in school-aged children up to 18 years of age. To update a part of
      a previously published Cochrane systematic review. SEARCH STRATEGY: Relevant
      evidence (up to 2002) was selected from the previous Cochrane review. Later
      studies, to July 2010, were identified from MEDLINE, Cochrane Central Register of
      Controlled Trials, EMBASE, Project CORK, and PsycINFO. SELECTION CRITERIA:
      Randomized trials evaluating universal multi-component prevention programs
      (intervention delivered in more than one setting) and reporting outcomes for
      alcohol use in students 18 years of age or younger were included. Two reviewers
      screened titles/abstracts and full text of identified records. DATA COLLECTION
      AND ANALYSIS: Two reviewers extracted relevant data independently using an a
      priori defined extraction form. Risk of bias was assessed. MAIN RESULTS: 20
      parallel-group trials were included. The reporting quality of trials was poor,
      only 25% and 5% of them reporting adequate method of randomisation and program
      allocation concealment, respectively. Incomplete data was adequately addressed in
      about half of the trials and this information was unclear for about 20% of the
      trials. Due to extensive heterogeneity across interventions, populations, and
      outcomes, the results were summarized only qualitatively.12 of the 20 trials
      showed some evidence of effectiveness compared to a control or other intervention
      group, with persistence of effects ranging from 3 months to 3 years. Of the
      remaining 8 trials, one trial reported significant effects using one-tailed tests
      and 7 trials reported no significant effects of the multi-component interventions
      for reducing alcohol misuse.Assessment of the additional benefit of multiple
      versus single component interventions was possible in 7 trials with multiple
      arms. Only one of the 7 trials clearly showed a benefit of components delivered
      in more than one setting. AUTHORS' CONCLUSIONS: There is some evidence that multi
      component interventions for alcohol misuse prevention in young people can be
      effective. However, there is little evidence that interventions with multiple
      components are more effective than interventions with single components.

PMID- 21901733
TI  - Universal family-based prevention programs for alcohol misuse in young people.
AB  - BACKGROUND: Alcohol misuse in young people is a cause of concern for health
      services, policy makers, prevention workers, and criminal justice system, youth
      workers, teachers, and parents. OBJECTIVES: To systematically review evidence on
      the effectiveness of universal family-based prevention programs in preventing
      alcohol misuse in school-aged children up to 18 years of age. To update a part of
      a previously published Cochrane systematic review. SEARCH STRATEGY: Relevant
      evidence (up to 2002) was selected from the previous Cochrane review. Later
      studies, to July 2010, were identified from MEDLINE, Cochrane Central Register of
      Controlled Trials, EMBASE, Project CORK, and PsycINFO. SELECTION CRITERIA:
      Randomized trials evaluating universal family-based prevention programs and
      reporting outcomes for alcohol use in students 18 years of age or younger were
      included. Two reviewers screened titles/abstracts and full text of identified
      records. DATA COLLECTION AND ANALYSIS: Two reviewers extracted relevant data
      independently using an a priori defined extraction form. Risk of bias was
      assessed. MAIN RESULTS: 12 parallel-group trials were included. The reporting
      quality of trials was poor, only 20% of them reporting adequate method of
      randomisation and program allocation concealment. Incomplete data was adequately
      addressed in about half of the trials and this information was unclear for about
      30% of the trials. Due to extensive heterogeneity across interventions,
      populations, and outcomes, the results were summarized only qualitatively.9 of
      the 12 trials showed some evidence of effectiveness compared to a control or
      other intervention group, with persistence of effects over the medium and longer
      term. Four of these effective interventions were gender-specific, focusing on
      young females. One study with a small sample size showed positive effects that
      were not statistically significant, and two studies with larger sample sizes
      reported no significant effects of the family-based intervention for reducing
      alcohol misuse. AUTHORS' CONCLUSIONS: In conclusion, in this Cochrane systematic
      review we found that that the effects of family-based prevention interventions
      are small but generally consistent and also persistent into the medium- to longer
      term.

PMID- 21901734
TI  - Social marketing interventions to increase HIV/STI testing uptake among men who
      have sex with men and male-to-female transgender women.
AB  - BACKGROUND: Social marketing interventions have been shown to both promote and
      change many health-related behaviours and issues. As the HIV epidemic continues
      to disproportionately affect MSM and transgender women around the world, social
      marketing interventions have the potential to increase HIV/STI testing uptake
      among these populations. OBJECTIVES: To assess the impact of social marketing
      interventions on HIV/STI testing uptake among men who have sex with men and
      transgender women compared to pre-intervention or control group testing uptake in
      the same population. SEARCH STRATEGY: We searched the following electronic
      databasesfor results from 01 January 1980 to the search date, 14 July 2010:
      Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, LILACS (Latin
      America and Brazil), PsycINFO, PubMed, Web of Science/Web of Social Science,
      Chinese National Knowledge Infrastructure (CNKI), and CQ VIP (China). We also
      searched for conference abstracts in the Aegis archive of HIV/AIDS conference
      abstracts and the CROI and International AIDS Society websites. In addition to
      searching electronic databases, we searched the following sources of grey
      literature: Australasian Digital Theses Program, Canadian Evaluation Society, 
      Eastview: China Conference Proceedings, ProQuest Dissertations and Theses, and
      World Health Organization Library Information System  (WHOLIS). We contacted
      individual researchers, experts working in the field, and authors of major trials
      for suggestions of any relevant manuscripts that were in preparation or in press.
      References of published articles from the databases above were searched for
      additional, pertinent materials. All languages were included in this search.
      SELECTION CRITERIA: Randomized controlled trials and controlled clinical trials
      that compared social marketing interventions with a control were included.
      Interrupted time series and pretest-posttest design studies (controlled or
      uncontrolled) that compared social marketing interventions with no intervention
      or a control were also included. Posttest-only studies and studies that combined
      pre-post data were excluded. Interventions that targeted at general public but
      did not include MSM or transgender women as a segment or did not have outcome
      data for an MSM or transgender segment were excluded. DATA COLLECTION AND
      ANALYSIS: Two authors independently extracted data from each included study and
      assessed study quality. Meta-analyses were conducted to compare pre- and post
      intervention and intervention and control group outcomes of HIV and STI testing
      uptake. Quality of evidence was assessed using the GRADE approach. MAIN RESULTS:
      Three serial, cross-sectional pretest-posttest study designs (one with a control
      group and two without) were included in the final analysis. Statistical pooling
      was conducted for two studies and compared to pre-intervention level testing
      uptake, which showed that multi-media social marketing campaigns had a
      significant impact on HIV testing uptake (OR=1.58, 95%CI = 1.40 - 1.77). However,
      the campaigns were not found to be effective in increasing STI testing uptake
      (OR=0.94, 95%CI = 0.68 - 1.28). Overall, risk of bias was high and quality of
      evidence was low. None of the studies were conducted in developing countries or
      included male-to-female transgender women. AUTHORS' CONCLUSIONS: This review
      provided limited evidence that multi-media social marketing campaigns can promote
      HIV testing among MSM in developed countries. Future evaluations of social
      marketing interventions for MSM should employ more rigorous study designs. Long
      term impact evaluations (changes in HIV or STI incidence over time) are also
      needed. Implementation research, including detailed process evaluation, is needed
      to identify elements of social marketing interventions that are most effective in
      reaching the target population and changing behaviours.

PMID- 21901735
TI  - Assessing rapid diagnostic tests for malaria.

PMID- 21901736
TI  - The use of Cochrane Reviews in NICE clinical guidelines.

PMID- 21901738
TI  - Glossary of bioinformatics terms.

PMID- 21901737
TI  - Blinded versus unblinded assessments of risk of bias in studies included in a
      systematic review.
AB  - BACKGROUND: The importance of appraising the risk of bias of studies included in
      systematic reviews is well-established. However, uncertainty remains surrounding
      the method by which risk of bias assessments should be conducted. Specifically,
      no summary of evidence exists as to whether blinded (i.e. the assessor is unaware
      of the study author's name, institution, sponsorship, journal, etc.) versus
      unblinded assessments of risk of bias yield systematically different assessments
      in a systematic review. OBJECTIVES: To determine whether blinded versus unblinded
      assessments of risk of bias yield systematically different assessments in a
      systematic review. SEARCH STRATEGY: We searched MEDLINE (1966 to September week 4
      2009), CINAHL (1982 to May week 3 2008), All EBM Reviews (inception to 6 October
      2009), EMBASE (1980 to 2009 week 40) and HealthStar (1966 to September week 4
      2009) (all Ovid interface). We applied no restrictions regarding language of
      publication, publication status or study design. We examined reference lists of
      included studies and contacted experts for potentially relevant literature.
      SELECTION CRITERIA: We included any study that examined blinded versus unblinded
      assessments of risk of bias included within a systematic review. DATA COLLECTION
      AND ANALYSIS: We extracted information from each of the included studies using a
      pre-specified 16-item form. We summarized the level of agreement between blinded
      and unblinded assessments of risk of bias descriptively. We calculated the
      standardized mean difference whenever possible. MAIN RESULTS: We included six
      randomized controlled trials (RCTs). Four studies had unclear risk of bias and
      two had high risk of bias. The results of these RCTs were not consistent; two
      demonstrated no differences between blinded and unblinded assessments, two found
      that blinded assessments had significantly lower quality scores, and another
      observed significantly higher quality scores for blinded assessments. The
      remaining study did not report the level of significance. We pooled five studies
      reporting sufficient information in a meta-analysis. We observed no statistically
      significant difference in risk of bias assessments between blinded or unblinded
      assessments (standardized mean difference -0.13, 95% confidence interval -0.42 to
      0.16). The mean difference might be slightly inaccurate, as we did not adjust for
      clustering in our meta-analysis. We observed inconsistency of results visually
      and noted statistical heterogeneity. AUTHORS' CONCLUSIONS: Our review highlights
      that discordance exists between studies examining blinded versus unblinded risk
      of bias assessments at the systematic review level. The best approach to risk of
      bias assessment remains unclear, however, given the increased time and resources
      required to conceal reports effectively, it may not be necessary for risk of bias
      assessments to be conducted under blinded conditions in a systematic review.

PMID- 21901740
TI  - Biological sequence motif discovery using motif-x.
AB  - The Web-based motif-x program provides a simple interface to extract
      statistically significant motifs from large data sets, such as MS/MS post
      translational modification data and groups of proteins that share a common
      biological function. Users upload data files and download results using common
      Web browsers on essentially any Web-compatible computer. Once submitted, data
      analyses are performed rapidly on an associated high-speed computer cluster and
      they produce both syntactic and image-based motif results and statistics. The
      protocols presented demonstrate the use of motif-x in three common user
      scenarios.

PMID- 21901739
TI  - Using the Saccharomyces Genome Database (SGD) for analysis of genomic
      information.
AB  - Analysis of genomic data requires access to software tools that place the
      sequence-derived information in the context of biology. The Saccharomyces Genome
      Database (SGD) integrates functional information about budding yeast genes and
      their products with a set of analysis tools that facilitate exploring their
      biological details. This unit describes how the various types of functional data
      available at SGD can be searched, retrieved, and analyzed. Starting with the
      guided tour of the SGD Home page and Locus Summary page, this unit highlights how
      to retrieve data using YeastMine, how to visualize genomic information with
      GBrowse, how to explore gene expression patterns with SPELL, and how to use Gene
      Ontology tools to characterize large-scale datasets.

PMID- 21901741
TI  - Gene identification in prokaryotic genomes, phages, metagenomes, and EST
      sequences with GeneMarkS suite.
AB  - This unit describes how to use several gene-finding programs from the GeneMark
      line developed for finding protein-coding ORFs in genomic DNA of prokaryotic
      species, in genomic DNA of eukaryotic species with intronless genes, in genomes
      of viruses and phages, and in prokaryotic metagenomic sequences, as well as in
      EST sequences with spliced-out introns. These bioinformatics tools were
      demonstrated to have state-of-the-art accuracy and have been frequently used for
      gene annotation in novel nucleotide sequences. An additional advantage of these
      sequence-analysis tools is that the problem of algorithm parameterization is
      solved automatically, with parameters estimated by iterative self-training
      (unsupervised training).

PMID- 21901742
TI  - Eukaryotic gene prediction using GeneMark.hmm-E and GeneMark-ES.
AB  - This unit describes how to use the gene-finding programs GeneMark.hmm-E and
      GeneMark-ES for finding protein-coding genes in the genomic DNA of eukaryotic
      organisms. These bioinformatics tools have been demonstrated to have state-of-the
      art accuracy for many fungal, plant, and animal genomes, and have frequently been
      used for gene annotation in novel genomic sequences. An additional advantage of
      GeneMark-ES is that the problem of algorithm parameterization is solved
      automatically, with parameters estimated by iterative self-training (unsupervised
      training).

PMID- 21901743
TI  - Using OrthoMCL to assign proteins to OrthoMCL-DB groups or to cluster proteomes
      into new ortholog groups.
AB  - OrthoMCL is an algorithm for grouping proteins into ortholog groups based on
      their sequence similarity. OrthoMCL-DB is a public database that allows users to
      browse and view ortholog groups that were pre-computed using the OrthoMCL
      algorithm. Version 4 of this database contained 116,536 ortholog groups clustered
      from 1,270,853 proteins obtained from 88 eukaryotic genomes, 16 archaean genomes,
      and 34 bacterial genomes. Future versions of OrthoMCL-DB will include more
      proteomes as more genomes are sequenced. Here, we describe how you can group your
      proteins of interest into ortholog clusters using two different means provided by
      the OrthoMCL system. The OrthoMCL-DB Web site has a tool for uploading and
      grouping a set of protein sequences, typically representing a proteome. This
      method maps the uploaded proteins to existing groups in OrthoMCL-DB.
      Alternatively, if you have proteins from a set of genomes that need to be
      grouped, you can download, install, and run the stand-alone OrthoMCL software.

PMID- 21901744
TI  - Involvement of the TGFbeta pathway in the regulation of alpha5 beta1 integrins by
      caveolin-1 in human glioblastoma.
AB  - Caveolin-1 plays a crucial role in the development of cancer and its progression.
      We previously reported that glioblastoma cells expressing low levels of caveolin
      1 exerted a more aggressive phenotype than cells expressing high levels. Such
      phenotype was due to the induction of alpha(5) beta(1)  integrin subsequent to
      the depletion of caveolin-1. Caveolin-1 was identified as a transcriptional
      repressor of alpha(5) beta(1)  integrin. The current study was designed to
      identify in vitro, the molecular mechanisms by which caveolin-1 controls alpha(5)
      beta(1)  integrin expression and to determine if a negative correlation between
      caveolin-1 and alpha(5) beta(1)  integrins also exists in biopsies and
      xenografted human brain tumors. We showed that depletion of caveolin-1 lead to
      the activation of the TGFbeta/TGFbetaRI/Smad2 pathway which in turn induced the
      expression of alpha(5) beta(1)  integrins. We showed that cells expressing the
      lowest levels of caveolin-1 but the highest levels of alpha(5) beta(1)  integrins
      and TGFbetaRI were the most sensitive to a alpha(5) beta(1)  integrin antagonist
      and a TGFbetaRI inhibitor. Screening human glioma biopsies and human glioblastoma
      xenografts, we isolated subgroups with either low levels of caveolin-1 but high
      levels of alpha(5) beta(1)  integrin and TGFbetaRI or high levels of caveolin-1
      but low levels of alpha(5) beta(1)  integrin and TGFbetaRI. In conclusion,
      caveolin-1 controls alpha(5) beta(1)  integrin expression through the
      TGFbeta/TGFbetaRI/Smad2 pathway. The status of caveolin-1/alpha(5) beta(1) 
      integrins/TGFbetaRI might be a useful marker of the tumor evolution/prognosis as
      well as a predictor of anti-TGFbeta or anti-alpha(5) beta(1)  integrin therapies.

PMID- 21901745
TI  - Frequent epigenetic inactivation of the chaperone SGNE1/7B2 in human gliomas.
AB  - In a genome-wide screen using DMH (differential methylation hybridization) we
      have identified a CpG island within the 5' region and untranslated first exon of
      the secretory granule neuroendocrine protein 1 gene (SGNE1/7B2) that showed
      hypermethylation in low- and high-grade astrocytomas compared to normal brain
      tissue. Pyrosequencing was performed to confirm the methylation status of this
      CpG island in 89 astrocytic gliomas of different malignancy grades and six glioma
      cell lines. Hypermethylation of SGNE1/7B2 was significantly more frequent in
      diffuse low-grade astrocytomas as well as secondary glioblastomas and anaplastic
      astrocytomas as compared to primary glioblastomas. mRNA expression analysis by
      real-time RT-PCR indicates that SGNE1/7B2 expression is downregulated in
      astrocytic gliomas compared to white matter samples. Treatment of glioma cells
      with the demethylating agent 5-aza-2'-deoxycytidine restores the transcription of
      SGNE1/7B2. Overexpression of SGNE1/7B2 in T98G, A172 and U373MG glioblastoma
      cells significantly suppressed focus formation and led to a significant increase
      in apoptotic cells as determined by flow cytometric analysis in T98G cells. In
      summary, we have identified SGNE1/7B2 as a novel target silenced by DNA
      methylation in astrocytic gliomas. The high incidence of this alteration and the
      significant effects of SGNE1/7B2 on the growth and apoptosis of glioblastoma
      cells provide a first proof for a functional implication of SGNE1/7B2
      inactivation in the molecular pathology of gliomas.

PMID- 21901747
TI  - Urokinase plasminogen activator receptor on invasive cancer cells: a prognostic
      factor in distal gastric adenocarcinoma.
AB  - Gastric cancer is the second cancer causing death worldwide. The five-year
      survival for this malignancy is below 25% and few parameters have shown an impact
      on the prognosis of the disease. The receptor for urokinase plasminogen activator
      (uPAR) is involved in extracellular matrix degradation by mediating cell surface
      associated plasminogen activation, and its presence on gastric cancer cells is
      linked to micrometastasis and poor prognosis. Using immunohistochemistry, the
      prognostic significance of uPAR was evaluated in tissue samples from a
      retrospective series of 95 gastric cancer patients. uPAR was expressed by
      neoplastic cells, macrophages, myofibroblasts and neutrophils in both intestinal
      and diffuse subtypes. No association was demonstrated between the expression of
      uPAR on cancer cells and histological subtype (p = 0.64) or TNM stage (p = 0.75).
      Univariate analysis revealed a significant association between the expression of
      uPAR on tumor cells in the peripheral invasion zone and overall survival of
      gastric cancer patients (HR = 2.16; 95% CI: 1.13-4.14; p = 0.02). Multivariate
      analysis showed that uPAR immunoreactivity in cancer cells at the invasive front
      is an independent prognostic factor for overall survival in gastric cancer (HR =
      2.39; 95% CI: 1.22-4.69; p = 0.011). In consequence, scoring of uPAR-positive
      cancer cells may be a direct measure for the invasive potential of gastric
      adenocarcinomas.

PMID- 21901746
TI  - Fibronectin attachment protein from bacillus Calmette-Guerin as targeting agent
      for bladder tumor cells.
AB  - The adjuvant therapy of choice for superficial bladder cancer is the intravesical
      instillation of live Mycobacterium bovis bacillus Calmette-Guerin (BCG). Despite
      the fact that this therapy is the most effective treatment for superficial
      bladder cancer, intravesical administration of BCG is associated with high local
      morbidity and the potential for systemic infection. Therefore, there is a need
      for the development of safer, less toxic approaches to fight this disease.
      Because fibronectin attachment protein (FAP) is a key element in BCG retention
      and targeting to cells, we hypothesize that this protein can be used as targeting
      agent to deliver cytotoxic cargo for the treatment of bladder tumors. Here, we
      evaluated the ability of bladder tumor cells to bind and endocytose FAP via
      fibronectin-integrin complexes. We found that microaggregation induced by an anti
      FAP polyclonal antibody accelerated FAP uptake by T24 bladder tumor cells. FAP
      was determined to be internalized via a clathrin-independent, caveolae-dependent
      mechanism. Furthermore, once within the endosomal compartment, FAP was targeted
      to the lysosomal compartment with negligible recycling to the plasma membrane.
      Importantly, we demonstrated that FAP microaggregation and internalization could
      also be triggered by multivalent Ni(2+) NTA-bearing liposomes. Overall, our
      studies validate the use of FAP as a targeting vector and provide the foundation
      for the design of more effective, less-toxic bladder cancer therapeutics.

PMID- 21901748
TI  - Molecular analysis of ceruloplasmin in a South African cohort presenting with
      oesophageal cancer.
AB  - Oesophageal cancer (OC) is a disease characterized by the development of
      malignant tumors in the epithelial cells lining the oesophagus. It demonstrates
      marked ethnic variation, with squamous cell carcinoma (SCC) being more prevalent
      in the Black population and adenocarcinoma (ADC) occurring more often in
      Caucasians. The etiology of this complex disease has been attributed to a variety
      of factors, including an excess of iron (resulting in increased tumourigenesis),
      oesophageal injury and inflammation (due in part to Barrett's oesophagus and
      smoking among others). The aim of this study was to determine if genetic
      variations identified in the ceruloplasmin (CP) gene (implicated in iron
      homeostasis) contribute to OC pathogenesis or susceptibility. The study cohort
      consisted of 96 unrelated OC patients from the Black Xhosa-speaking South African
      population and 88 population-matched control individuals. The promoter and coding
      regions of the CP gene were analyzed for DNA sequence variation using
      heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis,
      restriction fragment length polymorphism (RFLP) analysis and semi-automated
      bidirectional DNA sequencing analysis. Fourteen previously described and four
      novel variants were identified. Statistically significant associations were
      revealed for two of the novel variants with OC in this study and could,
      therefore, potentially contribute to disease susceptibility. In silico analysis
      of the region of the promoter spanning the identified variants sought to identify
      putative transcription factor binding sites (TFBSs) that could possibly regulate
      the expression of CP. To our knowledge, this is the first study to examine CP
      with respect to OC in the Black South African population.

PMID- 21901749
TI  - Theoretical and practical barriers to practitioners' willingness to seek training
      in empirically supported treatments.
AB  - To identify barriers to the dissemination of empirically supported treatments
      (ESTs), a random sample of psychologists in independent practice (N=1291) was
      asked to complete measures of attitudes towards ESTs and willingness to attend a
      3-hour, 1-day, or 3-day workshop in an EST of their choice. The strongest
      predictor of unwillingness to obtain EST training was the amount of time and cost
      required for the workshop, followed by objections to the need for EST training.
      Psychodynamic (compared to cognitive-behavioral) and more experienced
      practitioners agreed more strongly with the objections to ESTs overall, as did
      those whose graduate schools had not emphasized psychotherapy research. Results
      suggest that both practical and theoretical barriers are significant obstacles to
      EST dissemination.

PMID- 21901750
TI  - A guide to stem cell identification: progress and challenges in system-wide
      predictive testing with complex biomarkers.
AB  - We have developed a first generation tool for the unbiased identification and
      characterization of human pluripotent stem cells, termed PluriTest. This assay
      utilizes all the information contained on a microarray and abandons the
      conventional stem cell marker concept. Stem cells are defined by the ability to
      replenish themselves and to differentiate into more mature cell types. As
      differentiation potential is a property that cannot be directly proven in the
      stem cell state, biologists have to rely on correlative measurements in stem
      cells associated with differentiation potential. Unfortunately, most, if not all,
      of those markers are only valid within narrow limits of specific experimental
      systems. Microarray technologies and recently next-generation sequencing have
      revolutionized how cellular phenotypes can be characterized on a systems-wide
      level. Here we discuss the challenges PluriTest and similar global assays need to
      address to fulfill their enormous potential for industrial, diagnostic and
      therapeutic applications.

PMID- 21901751
TI  - Genomic imprinting; the cost of mother's care.

PMID- 21901752
TI  - Study of in vitro interaction between tetrabromobisphenol A and bovine serum
      albumin by fluorescence spectroscopy.
AB  - The interaction between tetrabromobisphenol A (TBBPA) and bovine serum albumin
      (BSA) in simulated physiological conditions (pH = 7.4) was investigated by
      fluorescence spectroscopy. The results revealed that TBBPA caused the
      fluorescence quenching of BSA through a static quenching procedure. The binding
      constants (K) of TBBPA with BSA at 277, 298, and 310 K were obtained as 4.75 *
      10(5) L/mol, 5.63 * 10(5) L/mol, and 6.66 * 10(5) L/mol, respectively. There may
      be two binding sites of TBBPA on BSA. The enthalpy change (DeltaH), free energy
      change (DeltaG), and entropy change (DeltaS) of thermodynamic parameters
      indicated that the interaction between TBBPA and BSA was driven mainly by
      hydrophobic and electrostatic forces. Synchronous fluorescence spectra showed
      TBBPA binding slightly changed the conformation of BSA by decreasing its polarity
      and increasing its hydrophobicity. The results of the present study may provide
      valuable information for studying the distribution and toxicity mechanisms of
      TBBPA in vivo.

PMID- 21901753
TI  - Development of a hydroxyapatite coating containing silver for the prevention of
      peri-prosthetic infection.
AB  - We hypothesized that the electrochemical deposition of hydroxyapatite (EHA) can
      be used to incorporate silver (Ag), providing a controlled and sustained release
      of Ag ions at a bactericidal concentration. Six groups were investigated:
      electrochemical co-precipitation of HA and Ag (EHA/Ag); EHA pre-coated discs
      treated in AgN0(3) (EHA/AgN0(3)); plasma sprayed HA (PHA) pre-coated discs
      treated in AgN0(3) (PHA/AgN0(3)); EHA with 2 "layers" of Ag (EHA/Ag/2 layers);
      EHA coating only; and PHA coating only. Scanning electron microscopy (SEM) and
      energy dispersive X-ray (EDX) and X-ray diffraction (XRD) analyses quantified
      coating thickness, calcium/phosphorous ratio, and % atomic silver content,
      respectively. Inductively coupled plasma-mass spectrometry quantified the amount
      of Ag released in phosphate-buffered saline, and zone of inhibition tests on agar
      plates using a lawn of Staph aureus were quantified in each group. XRD and EDX
      analysis confirmed the presence of Ag in all coatings. EHA coated discs with two
      layers of Ag and the EHA discs soaked in AgN0(3) showed significantly higher
      zones of inhibition at all time points when compared with all other groups
      (except PHA/AgN0(3) on day 0). This study demonstrated that Ag ions can be
      incorporated into a HA coating using an electrochemical technique.

PMID- 21901754
TI  - EMG-driven modeling approach to muscle force and joint load estimations: case
      study in knee osteoarthritis.
AB  - It is important to know the magnitude and patterns of joint loading in people
      with knee osteoarthritis (OA), since altered loads are implicated in onset and
      progression of the disease. We used an EMG-driven forward dynamics model to
      estimate joint loads during walking in a subject with knee OA and a healthy
      control subject. Kinematic, kinetic, and surface EMG data were used to predict
      muscle forces using a Hill-type muscle model. The muscle forces were used to
      balance the frontal plane moment to obtain medial and lateral condylar loads.
      Loads were normalized to body weight (BWs) and the mean of three trials taken.
      The OA subject had greater medial and lower lateral loads compared to the control
      subject. Seventy-five to 80% of the total load was borne on the medial
      compartment in the control subject, compared to 90-95% in the OA subject. In
      fact, complete lateral unloading occurred during midstance for the OA subject.
      Loading for the healthy subject was consistent with the data from instrumented
      knee studies. In the future, the model can be used to analyze the impact of
      various interventions to reduce the loads on the medial compartment in people
      with knee OA.

PMID- 21901755
TI  - Cerebellar oligodendroglial cells have a mesencephalic origin.
AB  - While the origin of oligodendroglia in the prosencephalon and spinal cord has
      been extensively studied and accurately described, the origin of this cell type
      in the cerebellum is largely unknown. To investigate where cerebellar
      oligodendrocytes generate and which migratory pathways they follow to reach their
      final destination in the adult, in ovo transplants were performed using the
      quail/chick chimeric system. The chimeric embryos were developed up to HH43-49
      (17-19 days of incubation) to map the location of donor cells and analyze their
      phenotype by immunohistochemistry. As a result, mesencephalic homotopic and
      homochronic transplants generated cellular migratory streams moving from the
      grafted epithelium into the host cerebellum, crossing the isthmus mainly through
      the velum medullare and invading the central white matter. From here, these
      mesencephalic cells invaded all the layers of the cerebellar cortex except the
      granular layer. The majority of the cells were detected in the central and folial
      white matter, as well as in superficial regions of the internal granular layer,
      surrounding the Purkinje cells. In the latter case, the donor cells presented a
      Bergmann glial morphology and were Vimentin positive, while in other areas they
      were PLP and Olig2-positive, indicating an oligodendroglial fate. The combinatory
      analysis of the different grafts allowed us to propose the fate map of chick
      cerebellar oligodendroglia at the neural tube stage. As a result, the majority of
      the cerebellar oligodendrocytes originate from the parabasal plate of the
      mesencephalon.

PMID- 21901756
TI  - Dynamic motility of microglia: purinergic modulation of microglial movement in
      the normal and pathological brain.
AB  - Microglia have highly branched and motile cell processes and constantly screen
      the brain parenchyma under physiological conditions. In response to pathological
      stimuli, microglia exhibit morphological changes and migrate toward the lesioned
      site, where they play important roles in inflammatory reactions and neuronal
      damage. Within minutes of brain damage, microglial processes rapidly extend
      toward the injured site. The chemoattractive response is triggered by ATP
      released at the site of injury and the consequent activation of the purinergic
      receptor P2Y12R on microglia. In addition to the purinergic signals, various
      neuronal signaling molecules actively and negatively control microglial motility,
      which is important for regulating the functional activation of microglia in
      response to pathology. In this review, we focus on the dynamic motion of
      microglia and describe several key molecules regulating microglial motility in
      normal and pathological brain tissues.

PMID- 21901757
TI  - Expression and regulation of AC133 and CD133 in glioblastoma.
AB  - The biological significance of CD133 in glioblastoma is controversial. Above all,
      there is disagreement concerning the proper approach, the appropriate (cell)
      model and the suitable microenvironment to study this molecule, often leading to
      inconsistent experimental results among studies. In consideration of a primary
      need to dissect and to understand the CD133 phenotype in glioblastoma we
      performed a comprehensive analysis of CD133 expression and regulation in a large
      set of glioblastoma cell lines (n = 20) as well as in tumor xenografts. Our
      analysis considered alternatively spliced mRNA transcripts, different protein
      epitopes as well as varying sub-cellular localizations of CD133 and explored its
      regulation under pertinent micro-environmental conditions. CD133 mRNA and CD133
      protein could be detected in all relevant types of glioblastoma cell lines. In
      addition, we detected frequent intracellular CD133 protein accumulations located
      to the ER and/or Golgi apparatus but seemingly unrelated to particular CD133
      splice variants or protein epitopes. In contrast, membrane-bound expression of
      CD133 was restricted to tumor cells bearing the extracellular CD133 epitope
      AC133. Only in these cells, differentiation and oxygen levels clearly impacted on
      AC133 expression and to some extent also influenced CD133 mRNA and protein
      expression. Most importantly, however, modulation of AC133 levels could occur
      independently of changes in CD133 mRNA transcription, CD133 protein translation,
      protein retention or protein shedding. Our results suggest that the AC133
      epitope, rather than CD133 mRNA or protein, mirrors malignancy-related tumor
      traits such as tumor differentiation and local oxygen tension levels, and thus
      corroborate its role as a biologically relevant cancer marker.

PMID- 21901758
TI  - Nitric oxide induces the expression of the monocarboxylate transporter MCT4 in
      cultured astrocytes by a cGMP-independent transcriptional activation.
AB  - The monocarboxylate transporter MCT4 is a proton-linked carrier particularly
      important for lactate release from highly glycolytic cells. In the central
      nervous system, MCT4 is exclusively expressed by astrocytes. Surprisingly, MCT4
      expression in primary cultures of mouse cortical astrocytes is conspicuously low,
      suggesting that an external, nonastrocytic signal is necessary to obtain the
      observed pattern of expression in vivo. Here, we demonstrate that nitric oxide
      (NO), delivered by various NO donors, time- and dose-dependently induces MCT4
      expression in cultured cortical astrocytes both at the mRNA and protein levels.
      In contrast, NO does not enhance the expression of MCT1, the other astrocytic
      monocarboxylate transporter. The transcriptional effect of NO is not mediated by
      a cGMP-dependent mechanism as shown by the absence of effect of a cGMP analog or
      of a selective guanylate cyclase inhibitor. NO causes an increase in astrocytic
      lactate transport capacity which requires the enhancement of MCT4 expression as
      both are prevented by the use of a specific siRNA against MCT4. In addition,
      cumulated lactate release by astrocytes over a period of 24 h was also enhanced
      by NO treatment. Our data suggest that NO represents a putative intercellular
      signal to control MCT4 expression in astrocytes and in doing so, to facilitate
      lactate transfer to other surrounding cell types in the central nervous system.
      (c) 2011 Wiley-Liss, Inc.

PMID- 21901760
TI  - Enhancing photocurrent efficiencies by resonance energy transfer in CdTe quantum
      dot multilayers: towards rainbow solar cells.

PMID- 21901759
TI  - Toll-like receptor 2 (TLR2)-TLR9 crosstalk dictates IL-12 family cytokine
      production in microglia.
AB  - Microglia are the resident mononuclear phagocytes of the CNS parenchyma and
      represent an initial line of defense against invading microorganisms. Microglia
      utilize Toll-like receptors (TLRs) for pathogen recognition and TLR2 specifically
      senses conserved motifs of gram-positive bacteria including lipoproteins,
      lipoteichoic acids, and peptidoglycan (PGN) leading to cytokine/chemokine
      production. Interestingly, primary microglia derived from TLR2 knockout (KO) mice
      over-expressed numerous IL-12 family members, including IL-12p40, IL-12p70, and
      IL-27 in response to intact S. aureus, but not the less structurally complex TLR2
      ligands Pam3CSK4 or PGN. The ability of intact bacteria to augment IL-12 family
      member expression was specific for gram-positive organisms, since numerous gram
      negative strains were unable to elicit exaggerated responses in TLR2 KO
      microglia. Inhibition of SYK or IRAK4 signaling did not impact heightened IL-12
      family member production in S. aureus-treated TLR2 KO microglia, whereas PI3K,
      MAPK, and JNK inhibitors were all capable of restoring exaggerated cytokine
      expression to wild type levels. Additionally, elevated IL-12 production in TLR2
      KO microglia was ablated by a TLR9 antagonist, suggesting that TLR9 drives IL-12
      family member production following exposure to intact bacteria that remains
      unchecked in the absence of TLR2 signaling. Collectively, these findings indicate
      crosstalk between TLR2 and TLR9 pathways to regulate IL-12 family member
      production by microglia. The summation of TLR signals must be tightly controlled
      to ensure the timely cessation and/or fine tuning of cytokine signaling to avoid
      nonspecific bystander damage due to sustained IL-12 release.

PMID- 21901761
TI  - Simulation of vapor-phase deposition and growth of a pentacene thin film on C60
      (001).

PMID- 21901762
TI  - High-current-density monolayer CdSe/ZnS quantum dot light-emitting devices with
      oxide electrodes.

PMID- 21901763
TI  - Light emission from nanocrystalline Si inverse opals and controlled passivation
      by atomic layer deposited Al2O3.

PMID- 21901764
TI  - Low driving voltage, high quantum efficiency, high power efficiency, and little
      efficiency roll-off in red, green, and deep-blue phosphorescent organic light
      emitting diodes using a high-triplet-energy hole transport material.

PMID- 21901765
TI  - Nanogel star polymer architectures: a nanoparticle platform for modular
      programmable macromolecular self-assembly, intercellular transport, and dual-mode
      cargo delivery.

PMID- 21901766
TI  - Direct probing of nanodimensioned oxide multilayers with the aid of focused ion
      beam milling.

PMID- 21901767
TI  - Flexible inorganic nanostructure light-emitting diodes fabricated on graphene
      films.

PMID- 21901768
TI  - A tough silicon nitride ceramic with high thermal conductivity.

PMID- 21901769
TI  - Metal-ligand cooperation in the catalytic dehydrogenative coupling (DHC) of
      polyalcohols to carboxylic acid derivatives.
AB  - Several polyols, which are easily available from sugars through biochemical
      conversion or hydrogenolytic cleavage, are directly converted into carboxylic
      acids and amides. This efficient dehydrogenative coupling process, catalyzed by a
      rhodium(I) diolefin amido complex, is an attractive approach for the production
      of organic fine chemicals from renewable resources. This method tolerates the
      presence of several hydroxy groups and can be extended to the direct synthesis of
      lactams from the corresponding amino alcohols under mild conditions.

PMID- 21901770
TI  - The absolute configuration of the pyrrolosesquiterpenoid glaciapyrrol A.
AB  - The total syntheses of the structurally unique and moderately cytotoxic
      pyrrolosesquiterpenoid glaciapyrrol A that has been isolated from a marine
      streptomycete by Macherla et al. and of seven of its stereoisomers have been
      performed from geraniol or nerol, respectively, using a known diastereoselective
      Ru-catalysed approach for the synthesis of tetrahydrofurans previously reported
      by Stark and co-workers. Comparison of (1)H and (13)C NMR data unambiguously
      clarified the relative configuration of natural glaciapyrrol A that was
      previously only partly solved from the available NMR data. An enantioselective
      synthesis was carried out resulting in the unnatural enantiomer (11S,12R,15R)-(-)
      glaciapyrrol A. These data establish the absolute configuration of the natural
      product as (11R,12S,15S)-(+)-glaciapyrrol A.

PMID- 21901771
TI  - Acid-catalyzed reactions of twisted amides in water solution: competition between
      hydration and hydrolysis.
AB  - The acid-catalyzed reactions of twisted amides in water solution were
      investigated by using cluster-continuum model calculations. In contrast to the
      previous widely suggested concerted hydration of the C=O group, our calculations
      show that the reaction proceeds in a practically stepwise manner, and that the
      hydration and hydrolysis channels of the C-N bond compete. The Eigen ion
      (H(3)O(+)) is the key species involved in the reaction, and it modulates the
      hydration and hydrolysis reaction pathways. The phenyl substitution in the
      twisted amide not only activates the N-CO bond, but also stabilizes the
      hydrolysis product through n(N)->pi(phenyl) delocalization, leading exclusively
      to the hydrolysis product of the ring-opened carboxylic acid. Generally, the
      twisted amides are more active than the planar amides, and such a rate
      acceleration results mainly from the increase in exothermicity in the first N
      protonation step; the second step of the nucleophilic attack is less affected by
      the twisting of the amide bond. The present results show good agreement with the
      available experimental observations.

PMID- 21901772
TI  - Perchloropyracylene and its fusion with C60 by chlorine-assisted radio-frequency
      furnace synthesis.
AB  - Elusive perchloropyracylene has been obtained during conventional fullerene
      synthesis in a chlorine-containing atmosphere by using the radio-frequency
      furnace technique. In contrast to its hydrocarbon analogue, the title compound
      was found to be unexpectedly stable. Although the high stability of
      perchloropyracylene impedes its direct addition to C(60) fullerene, the
      corresponding adduct was found in the synthesis products extracted from the raw
      soot. Both new species were separated and unambiguously characterized by single
      crystal X-ray analysis. According to experimental observations and quantum
      chemical calculations, the addition of perchloropyracylene to the C(60) fullerene
      can only be realized by involving highly reactive species such as C(14) clusters
      displaying the pyracylene connectivity. Such a viable mechanism includes
      capturing of free or partially chlorinated C(14) clusters with pyracylene-type
      connectivity by the fullerene molecule and subsequent stabilization through
      chlorine addition. The data obtained provide experimental evidence for the
      presence of pyracylene-like C(14) clusters in the gas phase, which have evolved
      during the graphite vaporization process. According to the pentagon road
      mechanism, such clusters are regarded as crucial intermediates in fullerene
      formation.

PMID- 21901773
TI  - Exercises in pyrrolidine chemistry: gram scale synthesis of a Pro-Pro dipeptide
      mimetic with a polyproline type II helix conformation.
AB  - A practical and scalable synthesis of a Fmoc-protected tricyclic dipeptide
      mimetic (6), that is, a 1,4-diaza-tricyclo-[8.3.0(3,7)]-tridec-8-ene derivative
      resembling a rigidified di-L-proline in a polyproline type II (PPII) helix
      conformation, was developed. The strategy is based on a Ru-catalyzed ring-closing
      metathesis of a dipeptide (4) prepared by PyBOP coupling of cis-5-vinylproline
      tert-butylester (2) and trans-N-Boc-3-vinylproline (rac-3) followed by
      chromatographic diastereomer separation. Building block 2 was prepared from L
      proline in six steps via electrochemical C5-methoxylation, cyanation and
      conversion of the nitrile into a vinyl substituent. Building block rac-3 was
      prepared in five steps exploiting a Cu-catalyzed 1,4-addition of vinyl-MgBr to a
      2,3-dehydroproline derivative in the key step. In the course of the investigation
      subtle dependencies of protecting groups on the reactivity of the 2,3- and 2,5
      disubstituted pyrrolidine derivatives were observed. The configuration and
      conformational preference of several intermediates were determined by X-ray
      crystallography. The developed synthesis allows the preparation of substantial
      amounts of 6, which will be used in the search for new small molecules for the
      modulation of protein-protein interactions involving proline-rich motifs (PRDs).

PMID- 21901774
TI  - trans-[Pt(BCat')Me(PCy3)2]: an experimental case study of reductive elimination
      processes in Pt-Boryls through associative mechanisms.
AB  - A stable trans-(alkyl)(boryl) platinum complex trans-[Pt(BCat')Me(PCy(3))(2)]
      (Cat'=Cat-4-tBu; Cy=cyclohexyl=C(6)H(11)) was synthesised by salt metathesis
      reaction of trans-[Pt(BCat')Br(PCy(3))(2)] with LiMe and was fully characterised.
      Investigation of the reactivity of the title compound showed complete reductive
      elimination of Cat'BMe at 80  degrees C within four weeks. This process may be
      accelerated by the addition of a variety of alkynes, thereby leading to the
      formation of the corresponding eta(2) -alkyne platinum complexes, of which
      [Pt(eta(2)-MeCCMe)(PCy(3))(2)] was characterised by X-ray crystallography.
      Conversion of the trans-configured title compound to a cis derivative remained
      unsuccessful due to an instantaneous reductive elimination process during the
      reaction with chelating phosphines. Treatment of trans-[Pt(BCat')Me(PCy(3))(2)]
      with Cat(2)B(2) led to the formation of CatBMe and Cat'BMe. In the course of
      further investigations into this reaction, indications for two indistinguishable
      reaction mechanisms were found: 1) associative formation of a six-coordinate
      platinum centre prior to reductive elimination and 2) sigma-bond metathesis of B
      B and C-Pt bonds. Mechanism 1 provides a straightforward explanation for the
      formation of both methylboranes. Scrambling of diboranes(4) Cat(2)B(2) and
      Cat'(2)B(2) in the presence of [Pt(PCy(3))(2)], fully reductive elimination of
      CatBMe or Cat'BMe from trans-[Pt(BCat')Me(PCy(3))(2)] in the presence of sub
      stoichiometric amounts of Cat(2)B(2), and evidence for the reversibility of the
      oxidative addition of Cat(2)B(2) to [Pt(PCy(3))(2)] all support mechanism 2,
      which consists of sequential equilibria reactions. Furthermore, the solid-state
      molecular structure of cis-[Pt(BCat)(2)(PCy(3))(2)] and cis
      [Pt(BCat')(2)(PCy(3))(2)] were investigated. The remarkably short B-B separations
      in both bis(boryl) complexes suggest that the two boryl ligands in each case are
      more loosely bound to the Pt(II) centre than in related bis(boryl) species.

PMID- 21901775
TI  - Control of the pharyngeal musculature during wakefulness and sleep: implications
      in normal controls and sleep apnea.
AB  - Respiration involves the complex coordination of several pump and upper
      airway/pharyngeal muscles. From a respiratory perspective, the major function of
      the pharyngeal muscles is to keep the airway patent allowing for airflow in and
      out of the lung with minimal work by the respiratory pump muscles. The activity
      of each of the pharyngeal muscles varies depending on its function, but many
      reduce their activity during sleep. In healthy individuals, these muscles can
      respond to respiratory stimuli during sleep to prevent airway collapse. However,
      in individuals with an anatomically small airway, the muscles cannot always
      compensate for the increased mechanical load. Thus a vulnerable situation in
      which the airway is prone to collapse may occur with the development of
      obstructive sleep apnea. This article describes the current understanding
      regarding the control of the pharyngeal musculature during wakefulness and sleep,
      as well as the implications for obstructive sleep apnea.

PMID- 21901776
TI  - An overview of therapies to promote repair of the brain after stroke.
AB  - Stroke remains a leading cause of disability. Most patients show some degree of
      spontaneous recovery, but this is generally incomplete. Studies on the
      neurobiology of this recovery are providing clues to therapeutic interventions
      that aim to improve patient outcomes. A number of potential such restorative
      therapies are reviewed. Numerous treatment strategies are under study. Most have
      a time window measured in days or weeks and so have the potential to help a large
      fraction of patients. This review considers these therapies, as well as points to
      consider in translating their application to human trials.

PMID- 21901777
TI  - Swallow remodeling of respiratory neural networks.
AB  - Swallow is defined as the coordinated neuromuscular activity of the mouth,
      pharynx, larynx, and esophagus. Movement of a bolus and air must be coordinated
      by swallow remodeling of the respiratory pattern. The brainstem contains
      respiratory and swallow neural control networks that generate the pattern for
      breathing and swallow. Swallow control of respiration is proposed to be through
      recruitment of swallow neural elements that retask existing respiratory neural
      network elements. Swallow reconfiguration of the respiratory neural network is
      fundamental to airway protection and integrated with other airway protective
      reflexes. Thus, swallow, breathing, cough, and other airway defensive behaviors
      are produced by a central neural motor system that shares elements. It is
      hypothesized that swallow and airway defensive behaviors are controlled by a
      recruited behavioral control assembly system that is organized in a fashion that
      allows for precise coordination of the expression of these behaviors to maintain
      airway protection.

PMID- 21901778
TI  - Introduction to the special issue, Integrative neural systems underlying vital
      aerodigestive tract functions. Madison, Wisconsin, June 17-19, 2010.

PMID- 21901779
TI  - Functional MRI of swallowing: from neurophysiology to neuroplasticity.
AB  - Swallowing is a complex neurogenic sensorimotor process involving all levels of
      the neuraxis and a vast number of muscles and anatomic structures. Disruption of
      any of these anatomic or functional components can lead to swallowing disorders
      (also known as dysphagia). Understanding the neural pathways that govern
      swallowing is necessary in diagnosing and treating patients with dysphagia.
      Functional MRI (fMRI) is a prevalent and effective neuroimaging method that has
      been used to study the complex neurophysiologic control of swallowing in vivo.
      This article presents a summary of the research studies that have used fMRI to
      study the neural control of swallowing in normal subjects and dysphagic patients,
      and to investigate the effects of swallowing treatments on neuroplasticity.
      Methodologic challenges and caveats are discussed, and a case study of a pre
      posttreatment paradigm is presented to highlight potential future directions of
      fMRI applications in swallowing research and clinical practice.

PMID- 21901780
TI  - Central nervous system control of interactions between vocalization and
      respiration in mammals.
AB  - The purpose of this review is to examine what is known regarding the competition
      and synergy between respiratory and airway protective systems with vocalization
      for speech. It was demonstrated that there are integrative neural mechanisms
      between vocalization for speech and upper airway protective mechanisms at both
      the brainstem levels and within cerebral networks. When there is competition
      between cortical control of learned volitional tasks, usually the upper airway
      protective systems predominate (eg, the laryngeal adductor response overrides
      laryngeal muscle control for voice and respiratory tasks). On the other hand,
      volitional swallowing overrides the laryngeal adductor response. Possible
      mechanisms for enhanced control of upper airway systems and rehabilitation of
      abnormal other upper airway systems was also examined. Recently, intensive
      clinical training using volitional breathing and swallowing tasks has been shown
      to modulate hyper-reactive sensory driven reflexes such as cough and paradoxical
      vocal fold movement disorder secondary to laryngeal hypersensitivity.

PMID- 21901781
TI  - Protecting the airway during swallowing: what is the role for afferent
      surveillance?
AB  - Mechanoreceptors are ubiquitous throughout the upper aerodigestive tract and
      provide spatiotemporal information on movement and stretch of muscles and
      connective tissues involved in feeding. Experimental studies in humans suggest
      that upper airway sensory signals provide important tonic and kinesthetic
      feedback to central neural circuits underlying upper airway perception and
      laryngeal closure during swallowing. These circuits include brainstem and
      cortical feedforward loops that facilitate swallowing function. A clinical
      implication of this organization is the potential to harness the sensory system
      for enhancing laryngeal closure during swallowing. Therapeutic sensory
      stimulation is a promising method for treating dysphagia and preventing
      aspiration pneumonia in patients with cortical lesions.

PMID- 21901782
TI  - Proceedings of the Integrative Neural Systems Underlying Vital Aerodigestive
      Tract Functions Conference, June 17-19, 2010: work group summary and call to
      action.

PMID- 21901783
TI  - Genome-wide linkage analysis of Swedish families to identify putative
      susceptibility loci for cutaneous malignant melanoma.
AB  - Cutaneous malignant melanoma is a clinically and genetically heterogeneous
      disorder which is caused by an interaction between hereditary and environmental
      factors. In Sweden, a small portion of the inherited susceptibility is explained
      by the presence of germline mutations in the tumor suppressor gene CDKN2A. But
      still, the genetic background of melanoma susceptibility is largely unknown.
      Here, we conducted a genome-wide linkage scan on melanoma-prone families using
      high-density single-nucleotide polymorphisms (SNPs) arrays to identify novel
      melanoma susceptibility genes. We investigated 35 families of Swedish origin
      without CDKN2A mutations. Nonparametric and parametric multipoint linkage
      analyses were performed. After removal of SNPs in strong linkage disequilibrium,
      the strongest evidence of linkage was detected on chromosome 17p11-12 (logarithm
      (base 10) of odds (LOD) scores of 2.76) using parametric linkage analysis
      assuming a dominant trait with full penetrance. Analyses were also performed on a
      subset of families with low age at diagnosis (mean age <= 47 years), to obtain a
      more homogenous subset. This subgroup analysis based on 22 families yielded
      suggestive evidence of linkage to the chromosomal regions 11p12-p11 and 18q22
      (multipoint LOD scores of 2.10 and 2.02, respectively). Also, the 17p region that
      was detected in the complete family set showed suggestive linkage in this cohort
      (multipoint LOD scores of 2.01). Our data suggest that these chromosomal regions,
      17p12-p11 in particular as it was present in both analyses, may harbor genes
      involved in the susceptibility of malignant melanoma in the Swedish population.

PMID- 21901784
TI  - Chd7 plays a critical role in controlling left-right symmetry during zebrafish
      somitogenesis.
AB  - Somitogenesis is a complex process during early vertebrate development involving
      interactions between many factors to form a bilateral somite series. A role for
      chromatin remodelers in somitogenesis has not yet been demonstrated. Here, we
      investigate the function of chromodomain helicase DNA binding protein 7 (chd7)
      during zebrafish somitogenesis. We show that Chd7 deficiency leads to asymmetric
      segmentation of the presomitic mesoderm (PSM), as revealed by expression of the
      somitogenesis genes, cdx1a, dlc, her7, mespa, and ripply1. Moreover, we show that
      abrogation of Chd7 results in the loss of asymmetric expression of spaw in the
      lateral plate mesoderm, which is consistent with more general laterality defects.
      Based on the observation that insufficient Chd7 leads to left-right asymmetry
      defects during PSM segmentation, and because CHD7 has been linked to human spinal
      deformities, we suggest that zebrafish chd7 morphants may be a good in vivo model
      to examine the pathophysiology of these diseases.

PMID- 21901786
TI  - MicroCT for molecular imaging: quantitative visualization of complete three
      dimensional distributions of gene products in embryonic limbs.
AB  - We present a broadly applicable procedure for whole-mount imaging of antibody
      probes in embryonic tissues at microscopic resolutions based on combining a metal
      based immunodetection scheme with x-ray microtomography (microCT). The method is
      generally accessible, relying on standard enzyme-conjugated secondary antibodies
      and other readily available reagents, and is demonstrated here with microCT
      visualizations of acetylated alpha-tubulin in the chick nervous system and of
      type II collagen in developing limbs. The tomographic images offer complete three
      dimensional representations of molecular patterns obtained with immunostaining
      methods at the level of organ development, with added possibilities to quantify
      both spatial distributions and varying densities of gene products in situ. This
      imaging modality bridges a crucial gap in three-dimensional molecular imaging by
      combining the histological resolutions of confocal microscopy with a greater
      specimen size range than optical projection tomography, and thus enables a
      powerful new approach to long-standing issues of skeletogenic pattern formation
      in vertebrate limbs.

PMID- 21901785
TI  - Epigenetic integration of the developing brain and face.
AB  - The integration of the brain and face and to what extent this relationship
      constrains or enables evolutionary change in the craniofacial complex is an issue
      of long-standing interest in vertebrate evolution. To investigate brain-face
      integration, we studied the covariation between the forebrain and midface at
      gestational days 10-10.5 in four strains of laboratory mice. We found that
      phenotypic variation in the forebrain is highly correlated with that of the face
      during face formation such that variation in the size of the forebrain correlates
      with the degree of prognathism and orientation of the facial prominences. This
      suggests strongly that the integration of the brain and face is relevant to the
      etiology of midfacial malformations such as orofacial clefts. This axis of
      integration also has important implications for the evolutionary developmental
      biology of the mammalian craniofacial complex.

PMID- 21901787
TI  - High prevalence of mutations in LCAT in patients with low HDL cholesterol levels
      in The Netherlands: identification and characterization of eight novel mutations.
AB  - Lecithin:cholesterol acyltransferase (LCAT) is crucial to the maturation of high
      density lipoprotein (HDL). Homozygosity for LCAT mutations underlies rare
      disorders characterized by HDL-cholesterol (HDL-c) deficiency while heterozygotes
      have half normal HDL-c levels. We studied the prevalence of LCAT mutations in
      referred patients with low HDL-c to better understand the molecular basis of low
      HDL-c in our patients. LCAT was sequenced in 98 patients referred for HDL-c <5th
      percentile and in four patients referred for low HDL-c and corneal opacities.
      LCAT mutations were highly prevalent: in 28 of the 98 participants (29%),
      heterozygosity for nonsynonymous mutations was identified while 18 patients
      carried the same mutation (p.T147I). The four patients with corneal opacity were
      compound heterozygotes. All previously identified mutations are documented to
      cause loss of catalytic activity. Nine novel mutations-c.402G>T (p.E134D),
      c.403T>A (p.Y135N), c.964C>T (p.R322C), c.296G>C (p.W99S), c.736G>T (p.V246F),
      c.802C>T (p.R268C), c.945G>A (p.W315X), c.1012C>T (p.L338F), and c.1039C>T
      (p.R347C)--were shown to be functional through in vitro characterization. The
      effect of several mutations on the core protein structure was studied by a three
      dimensional (3D) model. Unlike previous reports, functional mutations in LCAT
      were found in 29% of patients with low HDL-c, thus constituting a common cause of
      low HDL-c in referred patients in The Netherlands.

PMID- 21901788
TI  - Estimating the degree of identity by descent in consanguineous couples.
AB  - In some clinical and research settings, it is often necessary to identify the
      true level of "identity by descent" (IBD) between two individuals. However, as
      the individuals become more distantly related, it is increasingly difficult to
      accurately calculate this value. Consequently, we have developed a computer
      program that uses genome-wide SNP genotype data from related individuals to
      estimate the size and extent of IBD in their genomes. In addition, the software
      can compare a couple's IBD regions with either the autozygous regions of a
      relative affected by an autosomal recessive disease of unknown cause, or the IBD
      regions in the parents of the affected relative. It is then possible to calculate
      the probability of one of the couple's children suffering from the same disease.
      The software works by finding SNPs that exclude any possible IBD and then
      identifies regions that lack these SNPs, while exceeding a minimum size and
      number of SNPs. The accuracy of the algorithm was established by estimating the
      pairwise IBD between different members of a large pedigree with varying known
      coefficients of genetic relationship (CGR).

PMID- 21901790
TI  - Novel LOVD databases for hereditary breast cancer and colorectal cancer genes in
      the Chinese population.
AB  - The Human Variome Project (HVP) is an international consortium of clinicians,
      geneticists, and researchers from over 30 countries, aiming to facilitate the
      establishment and maintenance of standards, systems, and infrastructure for the
      worldwide collection and sharing of all genetic variations effecting human
      disease. The HVP-China Node will build new and supplement existing databases of
      genetic diseases. As the first effort, we have created a novel variant database
      of BRCA1 and BRCA2, mismatch repair genes (MMR), and APC genes for breast cancer,
      Lynch syndrome, and familial adenomatous polyposis (FAP), respectively, in the
      Chinese population using the Leiden Open Variation Database (LOVD) format. We
      searched PubMed and some Chinese search engines to collect all the variants of
      these genes in the Chinese population that have already been detected and
      reported. There are some differences in the gene variants between the Chinese
      population and that of other ethnicities. The database is available online at
      http://www.genomed.org/LOVD/. Our database will appear to users who survey other
      LOVD databases (e.g., by Google search, or by NCBI GeneTests search). Remote
      submissions are accepted, and the information is updated monthly.

PMID- 21901791
TI  - Identification and characterization of novel rare mutations in the planar cell
      polarity gene PRICKLE1 in human neural tube defects.
AB  - The planar cell polarity (PCP) pathway controls the process of convergent
      extension (CE) during gastrulation and neural tube closure, and has been
      implicated in the pathogenesis of neural tube defects (NTDs) in animal models and
      human cohorts. In this study, we analyzed the role of one core PCP gene PRICKLE1
      in these malformations. We screened this gene in 810 unrelated NTD patients and
      identified seven rare missense heterozygous mutations that were absent in all
      controls analyzed and predicted to be functionally deleterious using
      bioinformatics. Functional validation of five PRICKLE1 variants in a zebrafish
      model demonstrated that one variant, p.Arg682Cys, antagonized the CE phenotype
      induced by the wild-type zebrafish prickle1a (zpk1a) in a dominant fashion. Our
      study demonstrates that PRICKLE1 could act as a predisposing factor to human NTDs
      and further expands our knowledge of the role of PCP genes in the pathogenesis of
      these malformations.

PMID- 21901789
TI  - Whole-exome sequencing identifies ALMS1, IQCB1, CNGA3, and MYO7A mutations in
      patients with Leber congenital amaurosis.
AB  - It has been well documented that mutations in the same retinal disease gene can
      result in different clinical phenotypes due to difference in the mutant allele
      and/or genetic background. To evaluate this, a set of consanguineous patient
      families with Leber congenital amaurosis (LCA) that do not carry mutations in
      known LCA disease genes was characterized through homozygosity mapping followed
      by targeted exon/whole-exome sequencing to identify genetic variations. Among
      these families, a total of five putative disease-causing mutations, including
      four novel alleles, were found for six families. These five mutations are located
      in four genes, ALMS1, IQCB1, CNGA3, and MYO7A. Therefore, in our LCA collection
      from Saudi Arabia, three of the 37 unassigned families carry mutations in retinal
      disease genes ALMS1, CNGA3, and MYO7A, which have not been previously associated
      with LCA, and 3 of the 37 carry novel mutations in IQCB1, which has been recently
      associated with LCA. Together with other reports, our results emphasize that the
      molecular heterogeneity underlying LCA, and likely other retinal diseases, may be
      highly complex. Thus, to obtain accurate diagnosis and gain a complete picture of
      the disease, it is essential to sequence a larger set of retinal disease genes
      and combine the clinical phenotype with molecular diagnosis.

PMID- 21901793
TI  - Competitive amplification of differentially melting amplicons (CADMA) enables
      sensitive and direct detection of all mutation types by high-resolution melting
      analysis.
AB  - Sensitive and specific mutation detection is of particular importance in cancer
      diagnostics, prognostics, and individualized patient treatment. However, the
      majority of molecular methodologies that have been developed with the aim of
      increasing the sensitivity of mutation testing have drawbacks in terms of
      specificity, convenience, or costs. Here, we have established a new method,
      Competitive Amplification of Differentially Melting Amplicons (CADMA), which
      allows very sensitive and specific detection of all mutation types. The principle
      of the method is to amplify wild-type and mutated sequences simultaneously using
      a three-primer system. A mutation-specific primer is designed to introduce
      melting temperature decreasing mutations in the resulting mutated amplicon, while
      a second overlapping primer is designed to amplify both wild-type and mutated
      sequences. When combined with a third common primer very sensitive mutation
      detection becomes possible, when using high-resolution melting (HRM) as detection
      platform. The introduction of melting temperature decreasing mutations in the
      mutated amplicon also allows for further mutation enrichment by fast
      coamplification at lower denaturation temperature PCR (COLD-PCR). For proof-of
      concept, we have designed CADMA assays for clinically relevant BRAF, EGFR, KRAS,
      and PIK3CA mutations, which are sensitive to, between 0.025% and 0.25%, mutated
      alleles in a wild-type background. In conclusion, CADMA enables highly sensitive
      and specific mutation detection by HRM analysis.

PMID- 21901794
TI  - The role of the anterior cingulate cortex in emotional response inhibition.
AB  - Although the involvement of the anterior cingulate cortex (ACC) in emotional
      response inhibition is well established, there are several outstanding issues
      about the nature of this involvement that are not well understood. The present
      study aimed to examine the precise contribution of the ACC to emotion-modulated
      response inhibition by capitalizing on fine temporal resolution of the event
      related potentials (ERPs) and the recent advances in source localization. To this
      end, participants (N = 30) performed an indirect affective Go/Nogo task (i.e.,
      unrelated to the emotional content of stimulation) that required the inhibition
      of a motor response to three types of visual stimuli: arousing negative (A-),
      neutral (N), and arousing positive (A+). Behavioral data revealed that
      participants made more commission errors to A+ than to N and A-.
      Electrophysiological data showed that a specific region of the ACC at the
      intersection of its dorsal and rostral subdivisions was significantly involved in
      the interaction between emotional processing and motor inhibition. Specifically,
      activity reflecting this interaction was observed in the P3 (but not in the N2)
      time range, and was greater during the inhibition of responses to A+ than to N
      and A-. Additionally, regression analyses showed that inhibition-related activity
      within this ACC region was associated with the emotional content of the stimuli
      (its activity increased as stimulus valence was more positive), and also with
      behavioral performance (both with reaction times and commission errors). The
      present results provide additional data for understanding how, when, and where
      emotion interacts with response inhibition within the ACC.

PMID- 21901792
TI  - First implication of STRA6 mutations in isolated anophthalmia, microphthalmia,
      and coloboma: a new dimension to the STRA6 phenotype.
AB  - Microphthalmia, anophthalmia, and coloboma (MAC) are structural congenital eye
      malformations that cause a significant proportion of childhood visual
      impairments. Several disease genes have been identified but do not account for
      all MAC cases, suggesting that additional risk loci exist. We used single
      nucleotide polymorphism (SNP) homozygosity mapping (HM) and targeted next
      generation sequencing to identify the causative mutation for autosomal recessive
      isolated colobomatous microanophthalmia (MCOPCB) in a consanguineous Irish
      Traveller family. We identified a double-nucleotide polymorphism (g.1157G>A and
      g.1156G>A; p.G304K) in STRA6 that was homozygous in all of the MCOPCB patients.
      The STRA6 p.G304K mutation was subsequently detected in additional MCOPCB
      patients, including one individual with Matthew-Wood syndrome (MWS; MCOPS9).
      STRA6 encodes a transmembrane receptor involved in vitamin A uptake, a process
      essential to eye development and growth. We have shown that the G304K mutant
      STRA6 protein is mislocalized and has severely reduced vitamin A uptake activity.
      Furthermore, we reproduced the MCOPCB phenotype in a zebrafish disease model by
      inhibiting retinoic acid (RA) synthesis, suggesting that diminished RA levels
      account for the eye malformations in STRA6 p.G304K patients. The current study
      demonstrates that STRA6 mutations can cause isolated eye malformations in
      addition to the congenital anomalies observed in MWS.

PMID- 21901796
TI  - On the nature of chirality imparted to achiral polymers by the crystallization
      process.

PMID- 21901797
TI  - Improved stability and smart-material functionality realized in an energetic
      cocrystal.

PMID- 21901798
TI  - Copper-catalyzed intramolecular oxidative 6-exo-trig cyclization of 1,6-enynes
      with H2O and O2.

PMID- 21901799
TI  - Iridium diamine catalyst for the asymmetric transfer hydrogenation of ketones.

PMID- 21901800
TI  - Access to phosphorus-rich zirconium complexes.

PMID- 21901802
TI  - Wraparound hosts for fullerenes: tailored macrocycles and cages.
AB  - Custom-made macrocyclic receptors for fullerenes are proving a valuable
      alternative to achieve the affinity and selectivity required to meet challenges
      such as the selective extraction of higher fullerenes, their chiral resolution,
      or the self-assembly of functional molecular materials. In this Minireview, we
      highlight some of the important breakthroughs that this class of fullerene hosts
      has already produced.

PMID- 21901803
TI  - Simultaneous electronic and ionic conduction in a block copolymer: application in
      lithium battery electrodes.
AB  - Charging ahead: separate values for the simultaneous electronic and ionic
      conductivity of a conjugated polymer containing poly(3-hexylthiophene) and
      poly(ethylene oxide) (P3HT-PEO) were determined by using ac impedance and dc
      techniques. P3HT-PEO was used as binder, and transporter of electronic charge and
      Li(+) ions in a LiFePO(4) cathode, which was incorporated into solid-state
      lithium batteries.

PMID- 21901804
TI  - Vernier templating of nanoscopic porphyrin rings.

PMID- 21901805
TI  - Determination of the helical screw sense and side-group chirality of a synthetic
      chiral polymer from Raman optical activity.
AB  - Splitting it up: excellent agreement between the experimental and the quantum
      chemically simulated Raman optical activity (ROA) spectrum of (+)-poly(trityl
      methacrylate) shows that the polymer backbone adopts a left-handed helical
      conformation while the trityl side groups display a left-handed propeller
      conformation. Thus ROA can be used to determine the complete structure of
      synthetic chiral polymers in solution.

PMID- 21901806
TI  - Soluble heteropolyniobates from the bottom of Group IA.
AB  - Surprising solubility: While it is already well known that [Nb(6)O(19)](8-) salts
      exhibit an unusual solubility trend, that is, Cs>Rb>K>Na>Li, the
      heteropolyniobates of Cs and Rb had not yet been crystallized. These very soluble
      entities have now been obtained from solution by a simple and universal process.
      New polyoxoniobate geometries are thus unveiled, and the [SiNb(12)O(40)](16-)
      Keggin ion is characterized in solution for the first time.

PMID- 21901807
TI  - Modular redox-active inorganic chemical cells: iCHELLs.

PMID- 21901810
TI  - Simultaneous "one pot" expressed protein ligation and CuI-catalyzed azide/alkyne
      cycloaddition for protein immobilization.

PMID- 21901811
TI  - Metals (Ag(+) , Cd(2+) , Cr(6+) ) affect ATPase activity in the gill, kidney, and
      muscle of freshwater fish Oreochromis niloticus following acute and chronic
      exposures.
AB  - Freshwater fish Oreochromis niloticus were individually acutely exposed to
      different concentrations (0, 0.1, 0.5, 1.0, and 1.5 MUg/mL) of Cd(2+) , Cr(6+) ,
      and Ag(+) for 96 h and 0.05 MUg/mL concentration of the same metals for different
      periods (0, 5, 10, 20, and 30 days) chronically. Following each experimental
      protocol, Na(+) /K(+) -ATPase, Mg(2+) -ATPase, and Ca(2+) -ATPase activities were
      measured in the gill, kidney, and muscle of O. niloticus. In vitro experiments
      were also performed to determine the direct effects of metal ions (0, 0.1, 0.5,
      1.0, and 1.5 MUg/mL) on ATPases. Except Ag(+) , none of the metals caused fish
      mortality within 30 days. Silver killed all the fishes within 16 days. Metal
      exposures generally decreased Na(+) /K(+) -ATPase and Ca(2+) -ATPase activities
      in the tissues of O. niloticus, although there were some fluctuations in Mg(2+) 
      ATPase activity. Ag(+) and Cd(2+) were found to be more toxic to ATPase
      activities than Cr(6+) . It was also observed that metal efficiency was higher in
      the gill than in the other tissues. Results indicated that the response of
      ATPases varied depending on metals, exposure types, and tissues. Because ATPases
      are sensitive to metal toxicity, their activity can give valuable data about fish
      physiology. Therefore, they may be used as a sensitive biomarker in environmental
      monitoring in contaminated waters.

PMID- 21901812
TI  - Effects of decabromodiphenyl ether (BDE-209) on mRNA transcription of thyroid
      hormone pathway and spermatogenesis associated genes in Chinese rare minnow
      (Gobiocypris rarus).
AB  - Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants, which
      are ubiquitous environmental contaminant found in both abiotic and biotic
      environmental samples. Deca-BDE (BDE-209) is the principal component, which is
      currently used worldwide. In this study, the effect of BDE-209 on the mRNA levels
      of thyroid hormone (TH) related genes and spermatogenesis associated genes were
      determined from larvae and adult rare minnow (Gobiocypris rarus) exposed to
      concentrations 0.01, 0.1, 1, and 10 MUg/L for 21 days. The results showed that
      the type II deiodinase (dio2) and sodium iodide symporter (nis) mRNA levels were
      significantly up-regulated in the larvae at 10 MUg/L treatment. In adult,
      histopathological observations showed that liver of female fish were degenerated
      at 10 MUg/L treatment, and inhibition of spermatogenesis were observed in testis
      of male fish. In addition, the thyroid hormone receptor alpha (tralpha), dio2,
      and nis mRNA levels in the liver of male and female fish were significantly up
      regulated, whereas dio2 and nis mRNA levels were significantly down-regulated in
      the brain. These results indicate that exposure to BDE-209 could result in tissue
      specific alternations of TH-related genes expression in adults. Moreover, the
      mRNA levels of the testis-specific apoptosis genes, the spermatogenesis
      associated 4 (spata4) and spermatogenesis-associated 17 (spata17), were down
      regulated at 10 MUg/L treatment in testis of male fish. Our results suggest that
      BDE-209 may pose threat to normal thyroid and reproductive function in fish.

PMID- 21901813
TI  - Glial glutamate transporters: new actors in brain signaling.
AB  - Glutamate, the main excitatory amino acid in the vertebrate brain, is critically
      involved in most of the physiological functions of the central nervous system. It
      has traditionally been assumed that glutamate triggers a wide array of signaling
      cascades through the activation of specific membrane receptors. The extracellular
      levels are tightly regulated to prevent neurotoxic insults. Electrogenic Na(+)
      dependent glial glutamate transporters remove the bulk of the neurotransmitter
      from the synaptic cleft. An exquisitely ordered coupling between glutamatergic
      neurons and surrounding glia cells is fundamental for excitatory transmission.
      The glutamate/glutamine and astrocyte/neuron lactate shuttles provide the
      biochemical framework of this compulsory association. In this context, recent
      advances show that glial glutamate transporters act as signal transducers that
      regulate the expression of proteins involved in their compartmentalization with
      neurons in the so-called tripartite synapse.

PMID- 21901814
TI  - Neural integration of reward, arousal, and feeding: recruitment of VTA, lateral
      hypothalamus, and ventral striatal neurons.
AB  - The ability to control neuronal activity using light pulses and optogenetic tools
      has revealed new properties of neural circuits and established causal
      relationships between activation of a single genetically defined population of
      neurons and complex behaviors. Here, we briefly review the causal effect of
      activity of six genetically defined neural circuits on behavior, including the
      dopaminergic neurons DA in the ventral tegmental area (VTA); the two main
      populations of medium-sized spiny neurons (D1- and D2-positive) in the striatum;
      the giant Cholinergic interneurons in the ventral striatum; and the hypocretin-
      and MCH- expressing neurons in the lateral hypothalamus. We argue that selective
      spatiotemporal recruitment and coordinated spiking activity among these cell type
      specific neural circuits may underlie the neural integration of reward, learning,
      arousal and feeding.

PMID- 21901815
TI  - Calcium-regulated transcriptional pathways in the normal and pathologic heart.
AB  - The cytosolic calcium concentration ([Ca(2+)](c)) is key for the regulation of
      many cellular processes, such cell signaling and proliferation, metabolism, and
      muscle contraction. In cardiomyocytes, Ca(2+) is an important regulator in many
      cellular functions such electrophysiological processes, excitation-contraction
      coupling, regulation of contractile proteins activity, energy metabolism, cell
      death, and transcriptional regulation by the activation of Ca(2+)-dependent
      transcriptional pathways. In cardiomyocytes, the two main Ca(2+) -dependent
      pathways are the Ca(2+)/calmodulin-calcineurin-NFAT and the Ca(2+) /calmodulin
      dependent kinases-MEF2. Both pathways are involved in the transcriptional control
      of many cardiac genes. Cardiac hypertrophy (CH) and heart failure (HF) are
      characterized by alterations in calcium handling such a low sarcoplasmic
      reticulum Ca(2+) content, decreased rate of Ca(2+) removal from the sarcoplasm,
      increased diastolic [Ca(2+)](c), and decreased systolic [Ca(2+)](c), all of them
      contributing to diminished contractibility and force generation in failing heart.
      At gene expression level, there are also many changes such decreased levels of
      SERCA2a and activation of a fetal gene expression program in cardiomyocytes. A
      variety of Ca(2+)-dependent signaling pathways have been implicated in CH and HF,
      but whether these pathways are interrelated and whether there is specificity
      among them are still unclear and under investigation. The focus of this review is
      to make an analysis of the current knowledge about the role of Ca(2+) signaling
      pathways in the regulation of cardiac gene expression making special emphasis in
      novel strategies to correct Ca(2+) handling alterations by means of SERCA2a gene
      therapy.

PMID- 21901816
TI  - SOC and now also SIC: store-operated and store-inhibited channels.
AB  - There is a specialized form of calcium influx that involves a close communication
      between endoplasmic reticulum and the channels at the plasma membrane. In one
      side store depletion activates channels known as store-operated channels (SOC),
      which are responsible of the well-studied store-operated calcium entry (SOCE).
      SOC comprises two different types of channels. Orai, which is exclusively
      activated by store depletion being the channel responsible of the calcium release
      activated calcium current, and transient receptor potential canonical channel,
      which in contrast, is activated by store depletion only under specific conditions
      and carries nonselective cationic currents. On the other hand, it has been
      recently shown that store depletion also inhibits calcium channels. The first
      member identified, of what we named as store-inhibited channels (SIC), is the L
      type voltage-gated calcium channel. Stores control both SOC and SIC by means of
      the multifunctional protein STIM1. The identification of SOC and SIC opens a new
      scenario for the role of store depletion in the modulation of different calcium
      entry pathways, which may satisfy different cellular processes.

PMID- 21901817
TI  - CD38 through the life of a murine B lymphocyte.
AB  - CD38 is a 45 kDa transmembrane receptor expressed in B lymphocytes and other
      cells from the immune system. It is involved in apoptosis, cell activation,
      differentiation, and proliferation. CD38 has been used extensively to classify
      various subpopulations of lymphocytes in both humans and mice. It has also been
      used as a marker of poor prognosis in some lymphoid pathologies. However, CD38 is
      not a marker but rather an ectoenzyme and a receptor, where it performs several
      functions. The CD38 signaling pathway has only been partially studied in various
      cells of the immune system, where apparently the signaling is different depending
      on the lineage and differentiation state of the cell, leading to distinct
      outcomes. In this review, we provide an overview of well-established roles of
      CD38 signaling B lymphocytes from mice. We also discuss areas that need further
      clarification to get a broader image of how CD38 performs different functions in
      B cells and to understand its role in B lymphocyte biology under normal versus
      pathological conditions.

PMID- 21901818
TI  - Signaling epigenetics: novel insights on cell signaling and epigenetic
      regulation.
AB  - Cells must be able to respond rapidly and precisely not only to changes in their
      external environment but also to developmental and differentiation cues to
      determine when to divide, die, or acquire a particular cell fate. Signal
      transduction pathways are responsible for the integration and interpretation of
      most of such signals into specific transcriptional states. Those states are
      achieved by the modulation of chromatin structure that activates or represses
      transcription at particular loci. Although a large variety of signal transduction
      pathways have already been described, much less is known about the crosstalk
      between signal transduction and its consequent changes in chromatin structure
      and, therefore, gene expression. Here we present some examples of the
      relationship between chromatin-associated proteins and important signal
      transduction pathways during critical processes like development,
      differentiation, and disease. There is a great diversity of epigenetic mechanisms
      that have unexpected interactions with signaling pathways to establish
      transcriptional programs. Moreover, there are also particular cases where
      signaling pathways directly affect important components of the epigenetic
      machinery. Based on such examples, we further propose future research directions
      linking cell signaling and epigenetics. It is foreseeable that analyzing the
      relationship between cell signaling and epigenetics will be a huge area for
      future development that will help us understand the complex process by which a
      cell is able to induce transcriptional changes in response to external and
      internal signals.

PMID- 21901819
TI  - Progesterone and 17beta-estradiol increase differentiation of mouse embryonic
      stem cells to motor neurons.
AB  - Embryonic stem (ES) cells have the capacity to differentiate into endodermal,
      mesodermal, and ectodermal lineages. Motor neuron (MN) differentiation of mouse
      ES cells involves embryoid bodies formation with addition of Sonic hedgehog and
      retinoic acid. In this work, using immunocytochemistry, flow cytometry, and
      quantitative RT-PCR, we investigated whether progesterone or 17beta-estradiol
      have inductive effects on ES cell-derived MN, as it has been demonstrated that
      these hormones modify proliferation and neural differentiation of pluripotent
      cells. When 100 nM progesterone was added during differentiation, we found higher
      proportions of MN, compared to the control condition; coincubation of
      progesterone with the progesterone receptor (PR) antagonist RU-486 caused a
      decrease in the number of MN to a percentage even lower than controls. The
      addition of nanomolar concentrations of 17beta-estradiol also significantly
      induced MN differentiation. This effect of estradiol was completely antagonized
      by addition of the general estrogen receptor (ER) antagonist ICI 182,780. To
      identify the ER subtype mediating the increase on MN differentiation, we
      incubated estradiol with the ER-alpha antagonist MPP or with the ER-beta blocker
      PHTPP. When we coincubated 17beta-estradiol with MPP, we found a significant
      decrease in the percentage of MN. In contrast, the coincubation of 17beta
      estradiol with PHTPP had no effect on the induction of MN differentiation. All
      these effects on cell number were confirmed by significant changes in the
      expression of the MN markers Islet-1 and Choline acetyl transferase, assessed by
      real-time RT-PCR. Cell proliferation in embryoid bodies was significantly
      enhanced by progesterone treatment. No changes in apoptotic cell death were found
      in differentiating cells after progesterone or 17beta-estradiol addition. Our
      findings indicate that progesterone and 17beta-estradiol induce a higher
      proportion of MN derived from mouse ES cells through intracellular PR and ER,
      respectively. Furthermore, the effect of estradiol was mediated by specific
      activation of ER-alpha.

PMID- 21901820
TI  - Molecular control of cell differentiation and programmed cell death during digit
      development.
AB  - During the hand plate development, the processes of cell differentiation and
      control of cell death are relevant to ensure a correct shape of the limb. The
      progenitor cell pool that later will differentiate into cartilage to form the
      digits arises from undifferentiated mesenchymal cells beneath the apical
      ectodermal ridge (AER). Once these cells abandon the area of influence of signals
      from AER and ectoderm, some cells are committed to chondrocyte lineage forming
      the digital rays. However, if the cells are not committed to chondrocyte lineage,
      they will form the prospective interdigits that in species with free digits will
      subsequently die. In this work, we provide the overview of the molecular
      interactions between different signaling pathways responsible for the formation
      of digit and interdigit regions. In addition, we briefly describe some
      experiments concerning the most important signals responsible for promoting cell
      death. Finally, on the basis that the interdigital tissue has chondrogenic
      potential, we discuss the hypothesis that apoptotic-promoting signals might also
      act as antichondrogenic factors and chondrogenic factors might operate as anti
      apoptotic factors.

PMID- 21901821
TI  - Artificial cell membrane-mimicking nanostructure facilitates efficient gene
      delivery through fusogenic interaction with the plasma membrane of living cells.

PMID- 21901822
TI  - Modulating the charge-transfer enhancement in GERS using an electrical field
      under vacuum and an n/p-doping atmosphere.
AB  - The modulation of charger-transfer (CT) enhancement in graphene-enhanced Raman
      scattering (GERS) by an electric field under different atmospheres is reported.
      The GERS spectra of cobalt phthalocyanine (CoPc) molecules were collected by in
      situ Raman measurements under ambient air, vacuum, NH(3)  atmosphere, and O(2) 
      atmosphere, in which the Fermi level of graphene was modulated by an electrical
      field effect (EFE). The Raman scattering intensities of adsorbed molecules can be
      tuned to be stronger or weaker as the graphene Fermi level down-shifts or up
      shifts under electrical field modulation. However, the Raman intensity modulation
      in GERS is seriously influenced by the hysteresis effect in graphene EFE, which
      makes the modulation ability small and shows strong gate voltage sweep rate
      dependence in ambient air. Fortunately, the hysteresis effect in graphene EFE can
      be decreased by performing the measurement under vacuum conditions, and thus the
      Raman modulation ability in GERS can be increased. Furthermore, compared with the
      vacuum condition, the Raman modulation ability shows an increase under an NH(3) 
      atmosphere, while it shows a decrease under an O(2)  atmosphere, which is due to
      the different Fermi level modulation region in different atmospheres. More
      interestingly, this Raman intensity modulation in GERS shows a hysteresis-like
      behavior that is the same as the graphene Fermi level modulation under the EFE in
      a different atmosphere. All these observations suggest that the Raman enhancement
      in GERS occurs through a charge-transfer (CT) enhancement mechanism and the CT
      process can be modulated by the graphene EFE. This technique will benefit the
      study of the basic properties of both graphene and chemical enhancement mechanism
      in surface-enhanced Raman spectroscopy (SERS).

PMID- 21901823
TI  - Resolving in situ specific-contact, current-crowding, and channel resistivity in
      nanowire devices: a case study with silver nanowires.

PMID- 21901824
TI  - Combining a nanowire SERRS sensor and a target recycling reaction for
      ultrasensitive and multiplex identification of pathogenic fungi.
AB  - Development of a rapid, sensitive, and multiplex pathogen DNA sensor enables
      early diagnosis and, subsequently, the proper treatment of infectious diseases,
      increasing the possibility to save the lives of infected patients. Here, the
      development of an ultrasensitive and multiplex pathogen DNA detection method that
      combines a patterned Au nanowire (NW)-on-film surface-enhanced resonance Raman
      scattering (SERRS) sensor with an exonuclease III-assisted target DNA recycling
      reaction is reported. Multiple probe DNAs are added to the target DNA solution,
      and among them, only the complementary probe DNA is selectively digested by
      exonuclease III, resulting in the decrease in its concentration. The digestion
      process is repeated by recycling of target DNAs. The decrease of the
      complementary probe DNA concentration is detected by SERRS. Combining the high
      sensitivity of the NW-on-film sensor and the target recycling reaction
      significantly improves DNA detection performance, resulting in the detection
      limit of 100 fM corresponding to 3 amole. By positioning Au NWs at specific
      addresses, multiple pathogen DNAs can be identified in a single step. Clinical
      sample tests with multiple genomic DNAs of pathogens show the potential of this
      sensor for practical diagnosis of infectious diseases.

PMID- 21901825
TI  - Field-induced nanolithography for patterning of non-fouling polymer brush
      surfaces.

PMID- 21901826
TI  - Covalent tethering of protruding arms for addressable DNA nanostructures.
AB  - Functionalization of self-assembled DNA nanostructures is of fundamental
      importance for the realization of their application in nanotechnology and
      biosensing. Approaches reported so far suffer from lack of general applicability
      and usually require careful system design to avoid poor yields in the assembly of
      target structures. A novel approach well suited for fabrication of addressable
      DNA superstructures is reported here to generate DNA tile motifs. The method is
      based on the covalent linkage of a single-stranded protruding arm (covPA) to one
      of the oligomers forming the tile. Subsequent to assembly of tile motifs and
      superlattices, the covPA can be addressed by hybridization with complementary
      oligonucleotides or DNA-protein conjugates. The covPA can be located at arbitrary
      positions in a given tile motif without changing the general design and without
      compromising the structural integrity of the tile. The covPA strategy can also be
      readily extended to different PA sequences and multiple covPA arms can be linked
      to a tile. Superlattices obtained by self-assembly of covPA tiles reveal partial
      folding into double layers which possess an intrinsic order at the
      ultrastructural level. This phenomenon is likely associated with the increased
      flexibility of the covPA and might open up novel ways for DNA-based
      functionalization of solid surfaces and other applications of structural DNA
      nanotechnology.

PMID- 21901827
TI  - Reversible pore-structure evolution in hollow silica nanocapsules: large pores
      for siRNA delivery and nanoparticle collecting.
AB  - The effective modulation of pore sizes for nanoporous silica nanoparticles still
      remains a great challenge not satisfactorily solved. In this paper, the pore
      sizes in the shell of hollow silica nanocapsules are well-tuned by a reversible
      Si-O bond breakage and reformation process under mildly alkaline conditions
      (e.g., Na(2) CO(3)  solution). The pores in nanosized hollow silica capsules can
      be modulated from 3.2 nm to larger than 10 nm by a novel, surfactant-directing
      alkaline-etching (SDAE) strategy. Interestingly, the pores can be fully filled
      through the regrowth of the dissoluted silicates by bonding to silanols (Si-OH)
      on the wall surface to generate the nonporous hollow silica nanocapsules. The
      large-sized pore hollow silica nanocapsules exhibit excellent siRNA-loading
      capabilities and intracellular transfection efficiencies in vitro. In addition,
      the large pores in the shell of hollow silica nanocapsules are explored as
      channels for collecting superparamagnetic, small-sized Fe(3) O(4)  nanoparticles
      as contrast agents for magnetic resonance imaging, initiating a special approach
      towards pore-size modulation and multifunctionalization of silica-based
      nanostructural materials for nanobiomedical applications.

PMID- 21901828
TI  - Self-assembled DNA-based fluorescence waveguide with selectable output.
AB  - Using the principle of self-assembly, a fluorescence-based photonic network is
      constructed with one input and two spatially and spectrally distinct outputs. A
      hexagonal DNA nanoassembly is used as a scaffold to host both the input and
      output dyes. The use of DNA to host functional groups enables spatial resolution
      on the level of single base pairs, well below the wavelength of light.
      Communication between the input and output dyes is achieved through excitation
      energy transfer. Output selection is achieved by the addition of a mediator dye
      intercalating between the DNA base pairs transferring the excitation energy from
      input to output through energy hopping. This creates a tool for selective
      excitation energy transfer on the nanometer scale with spectral and spatial
      control. The ability to direct excitation energy in a controlled way on the
      nanometer scale is important for the incorporation of photochemical processes in
      nanotechnology.

PMID- 21901829
TI  - Surface-confined synthesis of silver nanoparticle composite coating on
      electrospun polyimide nanofibers.
AB  - A methodology for fabricating hierarchical nanostructures by surface-confined
      synthesis of silver nanoparticles on electrospun polyimide nanofibers is
      reported. Through surface-confined imide cleavage at the dianhydride domain via
      immersion in an aqueous KOH solution, potassium polyamate coatings of accurately
      defined thickness are formed (at a rate of 25 nm h(-1) ). By utilizing the ion
      exchange capability of the polyamate resin, silver ions are introduced through
      immersion in an aqueous AgNO3 solution. Subsequent reduction of the metal ion
      species leads to the formation of nanoparticles at the fiber surface. Two modes
      of reduction, chemical and thermal, are investigated in the report, each leading
      to distinct morphologies of the nanoparticle coatings. Via thermal reduction, a
      composite surface layer consisting of monodisperse silver nanoparticles (average
      diameter 5.2 nm) embedded in a re-imidized polyimide matrix is achieved. In the
      case of chemical reduction, the reduction process occurs preferentially at the
      surface of the fiber, leading to the formation of silver nanoparticles anchored
      at the surface, though not embedded, in a polyamic acid matrix. By regulating the
      modification depth, control of the particle density on the fiber surface is
      established. In both reduction approaches, the polyimide nanofiber core exhibits
      maintained integrity.

PMID- 21901830
TI  - A portable, benchtop photolithography system based on a solid-state light source.

PMID- 21901831
TI  - Surface-driven DNA assembly of binary cubic 3D nanocrystal superlattices.

PMID- 21901832
TI  - Fabrication of multilayered microparticles by integrating layer-by-layer assembly
      and microcontact printing.

PMID- 21901833
TI  - Proteomics analyses of microvesicles released by Drosophila Kc167 and S2 cells.
AB  - Distinct types of vesicles are formed in eukaryotic cells that conduct a variable
      set of functions depending on their origin. One subtype designated circulating
      microvesicles (MVs) provides a novel form of intercellular communication and
      recent work suggested the release and uptake of morphogens in vesicles by
      Drosophila cells. In this study, we have examined cells of the hemocyte-like cell
      lines Kc167 and S2 and identified secreted vesicles in the culture supernatant.
      The vesicles were isolated and found to have characteristics comparable to
      exosomes and plasma membrane MVs released by mammalian cells. In wingless
      transfected cells, the full-length protein was detected in the vesicle isolates.
      Proteomics analyses of the vesicles identified 269 proteins that include various
      orthologs of marker proteins and proteins with putative functions in vesicle
      formation and release. Analogous to their mammalian counterparts, the subcellular
      origin of the vesicular constituents of both cell lines is dominated by membrane
      associated and cytosolic proteins with functions that are consistent with their
      localization in MVs. The analyses revealed a significant overlap of the Kc167 and
      S2 vesicle proteomes and confirmed a close correlation with non-mammalian and
      mammalian exosomes.

PMID- 21901834
TI  - Phosphatidyl myo-inositol mannosides mimics built on an acyclic or heterocyclic
      core: synthesis and anti-inflammatory properties.
AB  - Phosphatidyl myo-inositol mannosides (PIMs) are constituents of the mycobacterial
      cell wall and possess immunomodulatory activities. Certain PIM derivatives have
      immunoprotective activity and are of interest as anti-inflammatory agents. In
      order to identify simplified analogues of PIMs that retain this interesting
      activity, we have prepared a series of new analogues based either on an acyclic
      or on a heterocyclic scaffold that replaces the inositol moiety, and evaluated
      these compounds for their inhibition of LPS-induced release of NO and pro
      inflammatory cytokines by macrophages. It was found that the inositol moiety can
      be favourably replaced by an aza-cyclitol (trihydroxy-piperidine) or an oxa
      cyclitol (trihydroxy-tetrahydropyran) unit, and that the configuration of the OH
      carrying carbons does not play a significant role. The biological activity is
      reduced if the nitrogen atom is free in the aza-cyclitol unit.

PMID- 21901835
TI  - From catalysts to bioactive organometallics: do Grubbs catalysts trigger
      biological effects?

PMID- 21901836
TI  - Peculiarities of beta-pinene autoxidation.
AB  - The thermal oxidation of the renewable olefin beta-pinene with molecular oxygen
      was experimentally and computationally investigated. Peroxyl radicals abstract
      weakly bonded allylic hydrogen atoms from the substrate, yielding allylic
      hydroperoxides (i.e., myrtenyl and pinocarvyl hydroperoxide). In addition,
      peroxyl radicals add to the C=C bond of the substrate to form an epoxide. It was
      found that a relatively high peroxyl radical concentration, together with the
      high rate of peroxyl cross-reactions, make radical-radical reactions surprisingly
      important for this particular substrate. Approximately 60 % of these peroxyl
      cross-reactions lead to termination (radical destruction), keeping a radical
      chain length of approximately 4 at 10 % conversion. Numerical simulation of the
      reaction-based on the proposed reaction mechanism and known or predicted rate
      constants-demonstrate the importance of peroxyl cross-reactions for the formation
      of alkoxyl radicals, which are the precursor of alcohol and ketone products.

PMID- 21901838
TI  - Sexual differentiation and the neuroendocrine hypothesis of autism.
AB  - The phenotypic expression of autism spectrum disorders varies widely in severity
      and characteristics and it is, therefore, likely that a number of etiological
      factors are involved. However, one finding which has been found consistently is
      that there is a greater incidence of autism in boys than girls. Recently,
      attention has been given to the extreme male hypothesis-that is that autism
      behaviors are an extreme form of typical male behaviors, including lack of
      empathy and language deficits but an increase in so-called systemizing behaviors,
      such as attention to detail and collecting. This points to the possibility that
      an alteration during sexual differentiation of the brain may occur in autism.
      During sexual differentiation of the brain, two brain regions are highly sexually
      dimorphic-the amygdala and the hypothalamus. Both of these regions are also
      implicated in the neuroendocrine hypothesis of autism, wherein a balance between
      oxytocin and cortisol may contribute to the disorder. We are thus proposing that
      the extreme male hypothesis and the neuroendocrine hypothesis are in fact
      compatible in that sexual differentiation of the brain towards an extreme male
      phenotype would result in the neuroendocrine changes proposed in autism. We have
      preliminary data, treating developing rat pups with the differentiating hormone
      17-beta estradiol during a critical time and showing changes in social behaviors
      and oxytocin, to support this hypothesis. Further studies should be undertaken to
      confirm the role of extremes of normal sexual differentiation in producing the
      neuroendocrine changes associated with autism.

PMID- 21901837
TI  - Dystrophic serotonin axons in postmortem brains from young autism patients.
AB  - Autism causes neuropathological changes in varied anatomical loci. A coherent
      neural mechanism to explain the spectrum of autistic symptomatology has not been
      proposed because most anatomical researchers focus on point-to-point functional
      neural systems (e.g., auditory and social networks) rather than considering
      global chemical neural systems. Serotonergic neurons have a global innervation
      pattern. Disorders Research Program, AS073234, Program Project (JW). Their cell
      bodies are found in the midbrain but they project their axons throughout the
      neural axis beginning in the fetal brain. This global system is implicated in
      autism by animal models and by biochemical, imaging, pharmacological, and
      genetics studies. However, no anatomical studies of the 5-HT innervation of
      autistic donors have been reported. Our review presents immunocytochemical
      evidence of an increase in 5-HT axons in postmortem brain tissue from autism
      donors aged 2.8-29 years relative to controls. This increase is observed in the
      principle ascending fiber bundles of the medial and lateral forebrain bundles,
      and in the innervation density of the amygdala and the piriform, superior
      temporal, and parahippocampal cortices. In autistic donors 8 years of age and up,
      several types of dystrophic 5-HT axons were seen in the termination fields. One
      class of these dystrophic axons, the thick heavily stained axons, was not seen in
      the brains of patients with neurodegenerative diseases. These findings provide
      morphological evidence for the involvement of serotonin neurons in the early
      etiology of autism, and suggest new therapies may be effective to blunt
      serotonin's trophic actions during early brain development in children.

PMID- 21901839
TI  - Alterations in GABAergic biomarkers in the autism brain: research findings and
      clinical implications.
AB  - Autism is a pervasive developmental disorder characterized by repetitive
      stereotyped behavior, social-emotional deficits, and delayed or absent language
      abilities. There are known neuropathologies in the autism brain affecting limbic,
      cerebellar, and cortical structures but the neurochemical profile of affected
      individuals, revealed in postmortem tissue studies, is only recently emerging.
      One major component that appears highly impacted in autism is the GABAergic
      system. It is now apparent that there are widespread significant effects in many
      distributed regions in the autism brain revealed by histochemical,
      autoradiographic, and biochemical studies. The key synthesizing enzymes for GABA,
      glutamic acid decarboxylase type 65 and 67 (GAD65 and GAD67), are decreased in
      the cerebellum and closer examination of mRNA levels revealed that it is largely
      due to decreases in Purkinje cells and a subpopulation of larger dentate neurons
      as measured by in situ hybridization studies. Other cell types had either normal
      GAD levels (Golgi cells, smaller dentate interneurons, and stellate cells) or
      increased levels (basket cells). GABA receptor density, number, and protein
      expression are all decreased in the cerebellum and in select cortical areas.
      GABA(A) and GABA(B) subunit protein expression was significantly reduced in
      cerebellum, BA 9 and BA 40. Benzodiazepine binding sites were significantly
      reduced in the hippocampus and anterior cingulate cortex (BA 24). Taken together,
      data from these studies suggest that there is a marked dysregulation of the
      inhibitory GABA system in the autism brain affecting particular biomarkers
      localized to specific cell types and lamina likely influencing circuitry and
      behavior.

PMID- 21901840
TI  - Metabotropic glutamate receptor 5 upregulation in children with autism is
      associated with underexpression of both Fragile X mental retardation protein and
      GABAA receptor beta 3 in adults with autism.
AB  - Recent work has demonstrated the impact of dysfunction of the GABAergic signaling
      system in brain and the resultant behavioral pathologies in subjects with autism.
      In animal models, altered expression of Fragile X mental retardation protein
      (FMRP) has been linked to downregulation of GABA receptors. Interestingly, the
      autistic phenotype is also observed in individuals with Fragile X syndrome. This
      study was undertaken to test previous theories relating abnormalities in levels
      of FMRP to GABA(A) receptor underexpression. We observed a significant reduction
      in levels of FMRP in the vermis of adults with autism. Additionally, we found
      that levels of metabotropic glutamate receptor 5 (mGluR5) protein were
      significantly increased in vermis of children with autism versus age and
      postmortem interval matched controls. There was also a significant decrease in
      level of GABA(A) receptor beta 3 (GABRbeta3) protein in vermis of adult subjects
      with autism. Finally, we found significant increases in glial fibrillary acidic
      protein in vermis of both children and adults with autism when compared with
      controls. Taken together, our results provide further evidence that altered FMRP
      expression and increased mGluR5 protein production potentially lead to altered
      expression of GABA(A) receptors.

PMID- 21901841
TI  - Altered expression of tyrosine hydroxylase in the locus coeruleus noradrenergic
      system in citalopram neonatally exposed rats and monoamine oxidase a knock out
      mice.
AB  - In rodents, noradrenergic (NE) locus coeruleus (LC) neurons are well known to
      express tyrosine hydroxylase (TH) immunoreactivity. However, due to its very low
      enzyme activity, NE cortical fibers do not typically express TH immunoreactivity,
      thus dopamine-beta-hydroxylase (DBH) immunoreactivity is commonly utilized as a
      marker for NE cortical fibers. In this study, we performed double and/or triple
      immunofluorescent staining using antibodies against TH, DBH, and/or
      norepinephrine transporter (NET) to investigate the altered NE TH expression of
      cortical fibers in citalopram (CTM)-exposed rats and monoamine oxidase (MAO) A
      knock out (KO) mice. We have noted the following novel findings: (1) neonatal
      exposure to the selective serotonin reuptake inhibitor (SSRI) CTM enhanced NE TH
      immunoreactive fibers throughout the entire neocortex, and a few of them appeared
      to be hypertrophic; (2) slightly enhanced NE cortical TH immunoreactive fibers
      were also noted in MAO A KO mice, and many of them revealed varicosities compared
      with the rather smooth NE cortical TH immunoreactive fibers in wild-type (WT)
      mice; (3) LC dendrites of MAO A KO mice exhibited beaded morphology compared with
      the smooth LC dendrites in WT mice. Our findings suggest that both genetic and
      environmental factors during early development may play a critical role in the
      regulation and proper function of NE TH expression in the neocortex.

PMID- 21901842
TI  - Temporal and regional alterations in NMDA receptor expression in Mecp2-null mice.
AB  - Our previous postmortem study of girls with Rett Syndrome (RTT), a development
      disorder caused by MECP2 mutations, found increases in the density of N-Methyl-D
      aspartate (NMDA) receptors in the prefrontal cortex of 2-8-year-old girls,
      whereas girls older than 10 years had reductions in NMDA receptors compared with
      age-matched controls (Blue et al., Ann Neurol 1999b;45:541-545). Using [(3)H]-CGP
      to label NMDA-type glutamate receptors in 2- and 7-week old wild-type (WT), Mecp2
      null, and Mecp2-heterozygous (HET) mice (Bird model), we found that frontal areas
      of the brain also exhibited a bimodal pattern in NMDA expression, with increased
      densities of NMDA receptors in Mecp2-null mice at 2 weeks of age but decreased
      densities at 7 weeks of age. Visual cortex showed a similar pattern, while other
      cortical regions only exhibited changes in NMDA receptor densities at 2 weeks
      (retrosplenial granular) or 7 weeks (somatosensory). In thalamus of null mice,
      NMDA receptors were increased at 2 and 7 weeks. No significant differences in
      density were found between HET and WT mice at both ages. Western blots for NMDAR1
      expression in frontal brain showed higher levels of expression in Mecp2-null mice
      at 2 weeks of age but not at 1 or 7 weeks of age. Our mouse data support the
      notion that deficient MeCP2 function is the primary cause of the NMDA receptor
      changes we observed in RTT. Furthermore, the findings of regional and temporal
      differences in NMDA expression illustrate the importance of age and brain region
      in evaluating different genotypes of mice.

PMID- 21901843
TI  - Development of the skull of the pantropical spotted dolphin (Stenella attenuata).
AB  - We describe the bony and cartilaginous structures of five fetal skulls of
      Stenella attenuata (pantropical spotted dolphin) specimens. The specimens
      represent early fetal life as suggested by the presence of rostral tactile hairs
      and the beginnings of skin pigmentation. These specimens exhibit the
      developmental order of ossification of the intramembranous and endochondral
      elements of the cranium as well as the functional and morphological development
      of specific cetacean anatomical adaptations. Detailed observations are presented
      on telescoping, nasal anatomy, and middle ear anatomy. The development of the
      middle ear ossicles, ectotympanic bone, and median nasal cartilage is of interest
      because in the adult these structures are morphologically different from those in
      land mammals. We follow specific cetacean morphological characteristics through
      fetal development to provide insight into the form and function of the cetacean
      body plan. Combining these data with fossil evidence, it is possible to overlie
      ontogenetic patterns and discern evolutionary patterns of the cetacean skull.

PMID- 21901845
TI  - Special issue: new concepts in developing brain disorders-autism.

PMID- 21901844
TI  - Experimental strategies for investigating psychostimulant drug actions and
      prefrontal cortical function in ADHD and related attention disorders.
AB  - Amphetamine-like psychostimulant drugs have been used for decades to treat a
      variety of clinical conditions. Methylphenidate (MPH)-Ritalin(R) , a compound
      that blocks reuptake of synaptically released norepinephrine (NE) and dopamine
      (DA) in the brain, has been used for more than 30 years in low dose, long-term
      regimens to treat attention deficit-hyperactive disorder (ADHD) in juveniles,
      adolescents, and adults. Now, these agents are also becoming increasingly popular
      among healthy individuals from all walks of life (e.g., military, students) and
      age groups (teenagers thru senior citizens) to promote wakefulness and improve
      attention. Although there is agreement regarding the primary biochemical action
      of MPH, the physiological basis for its efficacy in normal individuals and ADHD
      patients is lacking. Study of the behavioral and physiological actions of
      clinically and behaviorally relevant doses of MPH in normal animals provides an
      opportunity to explore the role of catecholamine transmitters in prefrontal
      cortical function and attentional processes as they relate to normal operation of
      brain circuits and ADHD pathology. The goal of ongoing studies has been to: (1)
      assess the effects of low dose MPH on rodent performance in a well characterized
      sensory-guided sustained attention task, (2) examine the effects of the same low
      dose chronic MPH administration on task-related discharge of prefrontal cortical
      (PFC) neurons, and (3) investigate the effects of NE and DA on membrane response
      properties and synaptic transmission in identified subsets of PFC neurons.
      Combinations of these approaches can be used in adolescent, adult, and aged
      animals to identify the parameters of cell and neural circuit function that are
      regulated by MPH and to establish an overarching explanation of how MPH impacts
      PFC operations from cellular through behavioral functional domains.

PMID- 21901846
TI  - Insights into coronary artery development in model of maternal protein
      restriction in mice.
AB  - Programming of fetal development is considered to be an important risk factor for
      noncommunicable diseases of adulthood, including coronary heart disease (CHD).
      Aiming to investigate the association between maternal nutrition and the
      development of the coronary arteries (CAs) in staged mice embryos, C57BL/6 mice
      embryos from Stages 16 to 23 were taken from mothers fed a normal protein (NP) or
      low protein (LP) diet, and the CA were studied. Although the LP embryos had lower
      masses, they had faster heart growth rates when compared with the NP embryos. The
      subepicardial plexuses were observed earlier in the NP embryos (Stage 20) than in
      the LP ones (Stage 22; P < 0.01). Apoptotic nuclei were seen around the aortic
      peritruncal ring beginning at Stage 18 in the NP and LP embryos. FLK1(+) (fetal
      liver kinase 1 = VEGF-r2 or vascular endothelial growth factor receptor 2) cells
      had a homogeneous distribution in the NP embryos as early as Stage 18, whereas a
      similar distribution in the LP embryos was only seen at Stages 22 and 23.
      Maternal protein restriction in mice leads to a delay in the growth of the heart
      in the embryonic period modifying the development of the subepicardial
      peritruncal plexus and the apoptosis in the future coronary orifice region.

PMID- 21901847
TI  - Distribution and ultrastructure of afferent fibers in the parietal peritoneum of
      the rat.
AB  - The distribution and the ultrastructure of afferent fibers innervating the
      parietal peritoneum in the rat was studied with immunohistochemistry using an
      antiserum against the neuronal marker protein gene product 9.5. The
      immunoreactive fibers were distributed throughout the peritoneum. They generally
      ran straight and parallel to the intercostal nerves running in the abdominal
      muscles underlying the peritoneum. They sometimes branched and terminated by
      forming club-like endings. The number of nerve endings on the peritoneal surface
      was 3.25 +/- 1.66 mm(-2) . Electron microscopic observations revealed both
      unmyelinated and myelinated nerve fibers. The unmyelinated fibers were thin and
      about 1 MUm in diameter. Their endings formed slight swellings located just
      inside the peritoneal cell layer. The myelinated fibers often formed a bundle
      that was composed of two or three nerve fibers. Each myelinated fiber kept in
      contact with a Shwann cell and projected toward the peritoneal cavity. Finally,
      they penetrated the peritoneal cell layer to reach the peritoneal cavity. These
      fibers then made contacts with the peritoneal cells and became free from the
      myelin sheath. The ending had a club-like shape covered with collagen fibers, and
      contained many neurofilaments, a few mitochondria, but no synaptic vesicles.
      These results suggest that since the sensory endings are exposed at the
      peritoneal cavity, the sensory fibers are highly sensitive to somatic or
      nociceptive stimuli.

PMID- 21901848
TI  - Jaw adductor muscles across lepidosaurs: a reappraisal.
AB  - The exact homologies of tetrapod jaw muscles remain unresolved, and this provides
      a barrier for phylogenetic analysis and tracing character evolution. Here,
      lepidosaur jaw muscles are surveyed using direct examination of species from 23
      families and published descriptions of species from 10 families. A revised
      nomenclature is applied according to proposed homologies with Latimeria. Among
      lepidosaurs, variation was found in many aspects of jaw muscle anatomy. The
      superficial layers mm. levator and retractor anguli oris (LAO and RAO) are
      present in Sphenodon but not all squamates. The external jaw adductor muscles
      universally present in lepidosaurs are homologous with the main adductor muscle,
      A2, of Latimeria and include four layers: superficialis (A2-SUP), medialis (A2
      M), profundus (A2-PRO), and posterior (A2-PVM). The A2-SUP appears divided in
      Agamidae, Gekkota, Xantusiidae, and Varanidae. The A2-M is layered lateromedial
      in lizards but anteroposterior in snakes. The names pseudotemporalis (PS) and
      pterygomandibularis (PTM) are recommended for subdivisions of the internal
      adductors of reptiles and amphibians, because the homology of this muscle with
      the A3' and A3 " of Latimeria remains inconclusive. The intramandibularis of
      lepidosaurs and Latimeria (A-omega) are homologous. The distribution of six jaw
      muscle characters was found to plot more parsimoniously on phylogenies based on
      morphological rather than and molecular data. Character mapping indicates that
      Squamata presents reduction in the divisions of the A2-M, Scincoidea presents
      reduction or loss of LAO, and two apomorphic features are found for the Gekkota.

PMID- 21901849
TI  - Methylamphetamine synthesis: does an alteration in synthesis conditions affect
      the delta(13) C, delta(15) N and delta(2) H stable isotope ratio values of the
      product?
AB  - Conventional chemical profiling of methylamphetamine has long been employed by
      national forensic laboratories to determine the synthetic route and where
      possible the precursor chemicals used in its manufacture. This laboratory has
      been studying the use of stable isotope ratio mass spectrometry (IRMS) analysis
      as a complementary technique to conventional chemical profiling of fully
      synthetic illicit drugs such as methylamphetamine. As part of these
      investigations the stable carbon (delta(13) C), nitrogen (delta(15) N), and
      hydrogen (delta(2) H) isotope values in the precursor chemicals of ephedrine and
      pseudoephedrine and the resulting methylamphetamine end-products have been
      measured to determine the synthetic origins of methylamphetamine. In this study,
      results are presented for delta(13) C, delta(15) N, and delta(2) H values in
      methylamphetamine synthesized from ephedrine and pseudoephedrine by two synthetic
      routes with varying experimental parameters. It was demonstrated that varying
      parameters, such as stoichiometry, reaction temperature, reaction time, and
      reaction pressure, had no effect on the delta(13) C, delta(15) N, and delta(2) H
      isotope values of the final methylamphetamine product, within measurement
      uncertainty. Therefore the value of the IRMS technique in identifying the
      synthetic origin of precursors, such as ephedrine and pseudoephedrine, is not
      compromised by the potential variation in synthetic method that is expected from
      one batch to the next, especially in clandestine laboratories where manufacture
      can occur without stringent quality control of reactions.

PMID- 21901851
TI  - Autoimmune polyendocrine syndrome type 1: Utility of KCNRG autoantibodies as a
      marker of active pulmonary disease and successful treatment with rituximab.
AB  - Autoimmune polyendocrine syndrome type 1 (APS-1), also known as Autoimmune
      Polyendocrinopathy Candidiasis and Ectodermal Dysplasia (APECD) is a disorder
      caused by mutations in the autoimmune regulator (AIRE) gene. In some APS-1
      patients, significant pulmonary disease is observed. Autoantibodies directed
      against the potassium channel regulatory protein (KCNRG), found in epithelial
      cells of terminal bronchioles, have been suggested as a marker for pulmonary
      disease in APS-1 patients. We report two patients with APS-1; one with and one
      without lung disease. Patient 1 had multiple admissions for pneumonia and
      respiratory insufficiency, required non-invasive ventilation, and had findings of
      bronchiectasis on thoracic imaging and significant lymphocytic infiltrates of the
      airways on lung biopsy. To verify the autoimmune cause of pulmonary symptoms APS
      1 patients, both were tested in a blinded manner for the presence of
      autoantibodies to KCNRG in serum. We found that only Patient 1 had autoantibodies
      present. Additionally, Patient 1 had progressive disease despite treatment with
      several immunomodulating agents, including corticosteroids, azathioprine, and
      mycophenolate. Patient 1 had a lung biopsy performed which was consistent with B
      cell lymphocytic aggregates. Rituximab treatment was initiated with apparent good
      response. This report illustrates the practical use of KCNRG autoantibodies to
      identify APS-1 patients with pulmonary risk and the successful use of the
      monoclonal antibody, Rituximab, to treat pulmonary disease in APS-1 patients.

PMID- 21901854
TI  - Inpatient healthcare trends among adult cystic fibrosis patients in the U.S.
AB  - BACKGROUND: Adult cystic fibrosis (CF) patients are an expanding cohort that is
      taken care of in a variety of hospital settings including adult centers located
      within pediatric institutions. This study compared costs and discharge rates
      among adult CF patient hospitalizations in terms of location of hospitalization.
      METHODS: The 2007 Nationwide Inpatient Sample was utilized to identify adult CF
      patient admission data on patients aged 18-44. Data were separated into pediatric
      and adult facilities based on percentage discharge rate for patients >18. Primary
      outcomes measures were length of stay (LOS) and total hospital charges. Secondary
      predictors were geographic, primary payer, and co-morbidity effects on LOS and
      total hospital charges. RESULTS: LOS was higher for adult CF patient admissions
      in pediatric facilities compared to adult facilities by a mean of 2.5 days. Mean
      total hospital charges were not significantly different. Adult hospitals in the
      Western U.S. had a mean total charge more than $50,000 greater than any region in
      the U.S. Self-pay patients had significantly fewer hospital days and charges
      across all hospital types. Adult facilities had 7% more CF patients discharged
      home with home healthcare use. Depressed CF patients had longer LOS by 1.5 days
      regardless of facility type. CONCLUSIONS: LOS for adult CF inpatient admissions
      was significantly lower in adult facilities compared to pediatric facilities
      without a significant difference in hospital charges and is influenced by
      geographic hospital location. Depressed patients had longer lengths of stay
      regardless of facility type. Self-insured adult CF patients have a significant
      reduction in LOS and hospital charges when compared to all other payers
      regardless of hospital type.

PMID- 21901855
TI  - Hospital readmissions for newly discharged pediatric home mechanical ventilation
      patients.
AB  - BACKGROUND: Ventilator-dependent children have complex chronic conditions that
      put them at risk for acute illness and repeated hospitalizations. OBJECTIVES: To
      determine the 12-month incidence of and risk factors for non-elective readmission
      in children with chronic respiratory failure (CRF) after initiation on home
      mechanical ventilation (HMV) via tracheostomy. METHODS: A retrospective cohort
      study of 109 HMV patients initiated and followed at an university-affiliated
      children's hospital between 2003 and 2009. Patient characteristics are presented
      using descriptive statistics; generalized estimated equations are used to
      estimate adjusted odds ratios of select predictor variables for readmission.
      RESULTS: The 12-month incidence of non-elective readmission was 40%. Close to
      half of these readmissions occurred within the first 3 months post-index
      discharge. Pneumonia and tracheitis were the most common reasons for readmission;
      64% were pulmonary- or tracheostomy-related. Most demographic and clinical
      patient characteristics were not statistically associated with non-elective
      readmissions. Although, a change in the child's management within 7 days before
      discharge was associated readmissions shortly after index discharge. CONCLUSION:
      Non-elective readmissions of newly initiated pediatric HMV patients were common
      and likely multifactorial. Many of these readmissions were airway-related, and
      some may have been potentially preventable.

PMID- 21901856
TI  - Evolution of surfactant protein-D levels in children with ventilator-associated
      pneumonia.
AB  - RATIONALE: The pathobiology of ventilator-associated pneumonia (VAP) in children
      is poorly understood; investigation has been limited by lack of universally
      applied diagnostic criteria and reliable biomarkers for this condition.
      OBJECTIVES: We evaluated the clinical pulmonary infection score (CPIS) in
      diagnosing VAP and prospectively characterized the relationship between
      surfactant protein-D (SP-D) metabolism and VAP. METHODS: Children admitted to an
      Egyptian PICU requiring intubation were screened for the absence of primary
      pulmonary pathology. Thirty-nine children underwent two evaluations: during the
      first 36 hr following intubation and after 4 days of mechanical ventilation.
      During both, bronchoalveolar lavage fluid (BALF) was obtained for culture and SP
      D assay. CPIS was computed during the second evaluation. RESULTS: Optimum
      performance of the CPIS against BALF culture occurred at a cutoff value of 6,
      (ROC AUC of 0.89 +/- 0.05). Children who developed VAP had significantly higher
      SP-D levels, both preceding (129.9 +/- 33.5 ng/ml at the 1st BAL)-and following
      positive BALF culture (249.5 +/- 51.2 ng/ml at the 2nd BAL), compared to children
      whose BALF remained sterile (62.6 +/- 18.1 ng/ml and 64.9 +/- 9.4 ng/ml; P <
      0.001). This increase in SP-D levels was most evident in children infected with
      Pseudomonas aeruginosa compared to children with Klebsiella pneumonia or S.
      aureus. CONCLUSIONS: The CPIS performed well against BALF culture. We observed a
      bacterial species-specific difference in SP-D levels in children who developed
      VAP; this change preceded detection of infection by CPIS or BALF culture.

PMID- 21901857
TI  - Clinical predictors of nasal continuous positive airway pressure requirement in
      acute bronchiolitis.
AB  - INTRODUCTION: There is growing use of nasal continuous positive airway pressure
      ventilation (nCPAP) for infants with bronchiolitis, based on clinical assessment
      of severity. Despite this there have been no studies which identify clinical
      predictors for the requirement of nCPAP. OBJECTIVE: To identify clinical factors
      in infants with acute bronchiolitis in the emergency department (ED), which might
      predict a requirement for nCPAP following admission. MATERIALS AND METHODS:
      Retrospective review of pediatric ED case notes was conducted on bronchiolitis
      admissions to one dedicated Paediatric ED over a 12-month period. Potential
      predictors were identified through literature review. Data extraction of
      predictors was carried out and recorded for each case. Logistic regression was
      conducted for each variable to identify statistically significant predictors of
      nCPAP requirement. RESULTS: Twenty-eight (17%) of the 163 admitted infants
      received nCPAP. The strongest predictors of nCPAP requirement in were as follows:
      oxygen requirement within the ED (P < 0.001), lower oxygen saturation (P <
      0.001), younger age at presentation (P = 0.002), higher respiratory rate (P =
      0.002), higher heart rate (P = 0.003), lower Glasgow Coma Scale score (0.006),
      and younger gestational age (P = 0.024). CONCLUSION: We have identified clinical
      variables that were predictive of nCPAP requirement in infants admitted to our
      unit with bronchiolitis, oxygen requirement in the ED being the strongest single
      predictor. This is the first such study in the UK, and we hope it may be a
      starting point for further work that may provide an evidence base to aid
      clinicians in predicting the use of nCPAP in infants with bronchiolitis.

PMID- 21901858
TI  - Lower airway microbiology and cellularity in children with newly diagnosed non-CF
      bronchiectasis.
AB  - BACKGROUND: Infection and inflammation are important in the pathogenesis of
      bronchiectasis. However, there are few published data describing the lower airway
      microbiology and cellularity in children. METHODS: Children with non-cystic
      fibrosis (CF) bronchiectasis who underwent bronchoalveolar lavage (BAL) within 4
      weeks of diagnosis were identified by a retrospective patient-record review. The
      effects of infection (>=10(5) colony-forming units of respiratory bacteria/ml; or
      detectable Pseudomonas aeruginosa; mycobacteria, fungi, mycoplasma, or
      respiratory viruses) on airway cellularity and the impact of age, gender,
      indigenous status, immune function, radiographic involvement and antibiotic usage
      on infection risk were evaluated. RESULTS: Of 113 children [median age 63 months
      (IQR 32-95)] with newly diagnosed bronchiectasis, 77 (68%) had positive BAL
      cultures for respiratory bacterial pathogens. Haemophilus influenzae was most
      commonly detected, being present in 53 (47%) BAL specimens. P. aeruginosa was
      found in just 7 (6%) children, five of whom had an underlying disorder, while
      mycobacterial and fungal species were not detected. Respiratory viruses were
      identified in 14 (12%) children and Mycoplasma pneumoniae in two others. Overall,
      56 (49.5%) children fulfilled our definition of a lower airway infection and of
      these, 35 (63%) had more than one pathogen present. Compared to children without
      infection, children with infection had higher total cell counts (610 vs. 280 *
      10(6) /L), neutrophil counts (351 vs. 70 * 10(6) /L), and neutrophil percentages
      (69% vs. 34%). Age at diagnosis was most strongly associated with infection.
      CONCLUSIONS: BAL microbiology of children with newly diagnosed bronchiectasis is
      dominated by H. influenzae. In the absence of CF, isolation of P. aeruginosa may
      suggest a serious co-morbidity in this group. Airway neutrophilia is common,
      especially with higher bacterial loads.

PMID- 21901859
TI  - Infection with multiple viruses is not associated with increased disease severity
      in children with bronchiolitis.
AB  - BACKGROUND: The clinical relevance of parallel detection of multiple viruses by
      real-time polymerase chain reaction (RT-PCR) remains unclear. This study
      evaluated the association between the detection of multiple viruses by RT-PCR and
      disease severity in children with bronchiolitis. METHODS: Children less than 2
      years of age with clinical symptoms of bronchiolitis were prospectively included
      during three winter seasons. Patients were categorized in three groups based on
      disease severity; mild (no supportive treatment), moderate (supplemental oxygen
      and/or nasogastric feeding), and severe (mechanical ventilation). Multiplex RT
      PCR of 15 respiratory viruses was performed on nasopharyngeal aspirates. RESULTS:
      In total, 142 samples were obtained. Respiratory Syncytial virus (RSV) was the
      most commonly detected virus (73%) followed by rhinovirus (RV) (30%). In 58
      samples (41%) more than one virus was detected, of which 41% was a dual infection
      with RSV and RV. In RSV infected children younger than 3 months, disease severity
      was not associated with the number of detected viruses. Remarkably, in children
      older than 3 months we found an association between more severe disease and RSV
      mono-infections. CONCLUSION: Disease severity in children with bronchiolitis is
      not associated with infection by multiple viruses. We conclude that other
      factors, such as age, contribute to disease severity to a larger extent.

PMID- 21901860
TI  - Ventilation homogeneity improves with growth early in life.
AB  - Some studies have suggested that lung clearance index (LCI) is age-independent
      among healthy subjects early in life, which implies that ventilation distribution
      does not vary with growth. However, other studies of older children and
      adolescents suggest that ventilation becomes more homogenous with somatic growth.
      We describe a new technique to obtain multiple breath washout (MBWO) in sedated
      infants and toddlers using slow augmented inflation breaths that yields an
      assessment of LCI and the slope of phase III, which is another index of
      ventilation inhomogeneity. We evaluated whether ventilation becomes more
      homogenous with increasing age early in life, and whether infants with chronic
      lung disease of infancy (CLDI) have increased ventilation inhomogeneity relative
      to full-term controls (FT). FT (N = 28) and CLDI (N = 22) subjects between 3 and
      28 months corrected-age were evaluated. LCI decreased with increasing age;
      however, there was no significant difference between the two groups (9.3 vs. 9.5;
      P = 0.56). Phase III slopes adjusted for expired volume (S(ND)) increased with
      increasing breath number during the washout and decreased with increasing age.
      There was no significant difference in S(ND) between full-term and CLDI subjects
      (211 vs. 218; P = 0.77). Our findings indicate that ventilation becomes more
      homogenous with lung growth and maturation early in life; however, there is no
      evidence that ventilation inhomogeneity is a significant component of the
      pulmonary pathophysiology of CLDI.

PMID- 21901861
TI  - Respiratory effects associated with wood fuel use: a cross-sectional biomarker
      study among adolescents.
AB  - The use of wood as heating and cooking fuel can result in elevated levels of
      indoor air pollution, but to what extent this is related to respiratory diseases
      and allergies is still inconclusive. Here, we report a cross-sectional study
      among 744 school adolescents (median age 15 years) using as main outcomes
      respiratory symptoms and diseases, exhaled nitric oxide, total and aeroallergen
      specific IgE in serum, and two epithelial biomarkers in nasal lavage fluid (NALF)
      or serum, that is, Clara cell protein (CC16) and surfactant-associated protein D
      (SPD). Information about the wood fuel use and potential confounders was
      collected via a personal interview of the adolescent and a questionnaire filled
      out by the parents. Two approaches were used to limit the possible influence of
      confounders, that is, multivariate analysis using the complete study population
      or pairwise analysis of matched sub-populations obtained using an automated
      procedure. Wood fuel use was associated with a decrease of CC16 and an increase
      of SPD in serum, which resulted in a decreased serum CC16/SPD ratio (median -9%,
      P = 0.001). No consistent differences were observed for the biomarkers measured
      in exhaled breath or NALF. Wood fuel use was also associated with increased odds
      for asthma [odds ratio (OR) 2.2, 95% CI: 1.1-4.4, P = 0.02], hay fever (OR = 2.4,
      95% CI: 1.4-4.3, P = 0.002), and sensitization against pollen allergens (OR =
      2.1, 95% CI: 1.3-3.4, P = 0.002). The risks of respiratory tract infections, self
      reported symptoms, and sensitization against house-dust mite were not increased
      by wood fuel use. The increased risks of asthma, hay fever and aeroallergen
      sensitization, and the changes of lung-specific biomarkers consistently pointed
      towards respiratory effects associated with the use of wood fuel.

PMID- 21901862
TI  - Serial interferon-gamma release assay in children with latent tuberculosis
      infection and children with tuberculosis.
AB  - BACKGROUND: Interferon-gamma (IFN-gamma) release assay (IGRA) is used for
      diagnosis of latent tuberculosis infection (LTBI), and for serial testing of
      active tuberculosis (TB). The aim of this study was to evaluate the results of
      IGRA for diagnosis and treatment monitoring of children with LTBI and children
      with TB. IGRA was performed in BCG vaccinated children before and six months
      after the beginning of treatment. METHODS: A total of 59 BCG vaccinated children
      aged 4-18 years were investigated due to exposure to active TB. The participants
      were divided into two groups: Group 1, children with LTBI (N = 41), and Group 2,
      children with TB (N = 18). IGRA (QuantiFERON-TB Gold In-Tube) was performed
      twice, i.e., before treatment and at the end of prophylaxis and therapy. RESULTS:
      There was no significant difference in IFN-gamma concentrations between Group 1
      and Group 2 subjects either before or after the treatment. Difference between pre
      treatment and post-treatment IFN-gamma concentrations compared in either Group 1
      or Group 2 was not statistically significant. During follow-up, children with
      LTBI did not develop active TB. In addition, in children with TB, signs and
      symptoms of TB improved with anti-TB therapy. CONCLUSION: This study showed that
      the concentrations of IFN-gamma did not differ in children with LTBI and TB
      either before or at the end of treatment. IGRA may remain positive over a long
      period of time. It seems that IGRA is not useful for monitoring treatment of
      children with LTBI and children with TB.

PMID- 21901863
TI  - Use of a Plackett-Burman statistical design to determine the effect of selected
      amino acids on monoclonal antibody production in CHO cells.
AB  - Culture media design is central to the optimization of monoclonal antibody (mAb)
      production. Although general strategies do not currently exist for optimization
      of culture media, the combined use of statistical design and analysis of
      experiments and strategies based on simple material balances can facilitate
      culture media design. In this study, we evaluate the effect of selected amino
      acids on the growth rate and monoclonal antibody production of a Chinese hamster
      ovary DG-44 (CHO-DG44) cell line. These amino acids were selected based on their
      relative mass fraction in the specific mAb produced in this study, their
      consumption rate during bioreactor experiments, and also through a literature
      review. A Plackett-Burman statistical design was conducted to minimize the number
      of experiments needed to obtain statistically relevant information. The effect of
      this set of amino acids was evaluated during exponential cell culture
      (considering viable cell concentration and the specific growth rate as main
      output variables) and during the high cell-density stage (considering mAb final
      concentration and specific productivity as relevant output variables). For this
      particular cell line, leucine (Leu) and arginine (Arg) had the highest negative
      and positive effects on cell viability, respectively; Leu and threonine (Thr) had
      the highest negative effect on growth rate, and valine (Val) and Arg demonstrated
      the highest positive impact on mAb final concentration. Results suggest the
      pertinence of a two-stage strategy for amino acid supplementation, with a mixture
      optimized for cell growth and a different amino acid mixture for mAb production
      at high density.

PMID- 21901870
TI  - Haemosporidian vector research: marriage of molecular and microscopical
      approaches is essential.
AB  - Many species of malaria and related haemosporidian parasites (Haemosporida) are
      responsible for diseases in wild and domestic animals. These pathogens are
      exclusively transmitted by blood-sucking dipteran insects (Diptera). Traditional
      vector studies, which are based mainly on experimental infection and subsequent
      dissection of insects, are time-consuming, so progress in the identification of
      the vectors has been slow. Since the discovery of haemosporidians in wildlife by
      V. Danilewsky in 1884, it took over 70 years to determine the main vector groups
      of these parasites. However, precise vector-parasite relationships remain
      insufficiently investigated in wildlife, particularly at the species level of
      haemosporidians and their vectors. Molecular tools have provided innovative
      opportunities to speed such research. In this issue of Molecular Ecology,
      Martinez-de la Puente et al. (2011) collected, for the first time, a significant
      PCR-based set of data on the presence of lineages of the pigment-forming
      haemosporidians (species of Haemoproteus and Plasmodium) in biting midges
      (Culicoides). They identified numerous associations between Culicoides spp. and
      Haemoproteus spp., indicating directions for future targeting vector studies of
      haemoproteids.

PMID- 21901864
TI  - The full spectrum of physiological oxygen tensions and step-changes in oxygen
      tension affects the neural differentiation of mouse embryonic stem cells.
AB  - The beneficial impact of lowering oxygen tension to physiological levels has been
      demonstrated in a number of stem cell differentiation protocols. The majority of
      these studies compare normal laboratory oxygen tension with one physiological
      condition (typically 2-5% O(2) ). In this article, we investigated whether the
      full spectrum of physiological oxygen tensions (0-20% O(2) ) and step-changes in
      oxygen tension could enhance the production of neural populations from of
      embryonic stem cells (ESCs). We used a model system for the conversion of mouse
      ESCs into cells expressing one neuroectoderm stem cell marker (nestin) and two
      neural markers (betaIII tubulin and microtubule-associated protein (MAP2)). 4-10%
      O(2) was associated with large increases in the total production of viable cells
      and the highest number of cells expressing Nestin, betaIII tubulin, and MAP2.
      However, 4-10% O(2) also caused a reduction in the percentage of cells expressing
      all three markers. Step changes in oxygen tension at the mid-point of the
      differentiation process affected the total production of viable cells and the
      percentage of cells expressing all three markers. We found that the initial
      oxygen tension and the magnitude of the step-change were critical variables. A
      step increase from 0 to 2% O(2) mid-way through the protocol resulted in the
      highest percentage of cells expressing betaIII tubulin (86.5%). In conclusion, we
      have demonstrated that the full spectrum of physiological oxygen tensions and
      step changes in oxygen tension represent a powerful tool for the optimisation of
      neural differentiation processes.

PMID- 21901871
TI  - Co-infection and risk factors of tuberculosis in a Mexican HIV+ population.
AB  - INTRODUCTION: The situation of tuberculosis (TB) is being modified by the human
      immunodeficiency virus (HIV), which is increasing the occurrence of new cases and
      the generation of drug resistant strains, affecting not only the people infected
      with HIV, but also their close contacts and the general population, conforming a
      serious public health concern.However, the magnitudes of the factors associated
      to this co-infection differ considerably in relation to the population groups and
      geographical areas. METHODS: In order to evaluate the prevalence and risk factors
      for the co-infection of tuberculosis (TB) in a population with human
      immunodeficiency virus (HIV+) in the Southeast of Mexico, we made the analysis of
      clinical and epidemiological variables and the diagnosis of tuberculosis by
      isolation of mycobacteria from respiratory samples. RESULTS: From the 147 HIV+
      individuals analyzed, 12 were culture positive; this shows a prevalence of 8% for
      the co-infection. The only variable found with statistical significance for the
      co-infection was the number of CD4-T < 200 cells/mm3, OR 13(95%, CI 2-106 vs 12
      109). CONCLUSIONS: To our knowledge this is the first report describing the
      factors associated with tuberculosis co-infection with HIV in a population from
      Southern Mexico. The low number of CD4 T-cells was the only variable associated
      with the TB co-infection and the rest of the variables provide scenarios that
      require specific and particular interventions for this population group.

PMID- 21901872
TI  - Jonathan Rosand.

PMID- 21901873
TI  - Community prevalence of methicillin and vancomycin resistant Staphylococcus
      aureus in and around Bangalore, southern India.
AB  - INTRODUCTION: Staphylococcus aureus is a known colonizer in humans and has been
      implicated in community acquired soft tissue infections. However emergence of
      methicillin resistant S. aureus(MRSA) has aroused great concern worldwide. This
      study aimed to determine the prevalence of MRSA in the community of Bangalore,
      southern India. METHODS: Swabs were collected from anterior nares, forearm,
      dorsum and palm of the hands of 1,000 healthy individuals residing in and around
      Bangalore, belonging to different socioeconomic strata and age groups. RESULTS:
      Analysis verified that 22.5% and 16.6% of the individuals presented
      Staphylococcus aureus and MRSA, respectively, at any of the three sites.
      Vancomycin resistance was observed in 1.4% of the S. aureus isolates, which was
      confirmed by detection of the vanA gene. It was interesting to note that 58.8% of
      the children in the age group 1-5 years-old presented MRSA, the highest
      percentage compared to other age groups of < 1 (44.4%) year-old, 5-20 (21.7%)
      years-old, > 40(11%) years-old and 20-40 (9.9%) years-old. Among the population
      of various socioeconomic strata, maximum MRSA colonization was observed among
      doctors (22.2%), followed by upper economic class (18.8%), lower economic class
      (17.7%), apparently healthy hospital in-patients (16.5%), nurses (16%) and middle
      economic class (12.5%). Most of the MRSA isolates were capsular polysaccharide
      antigen type 8 (57.1%). CONCLUSIONS: There is a need for continuous surveillance
      and monitoring of the presence of MRSA in the community and a clearer
      understanding of the dynamics of the spread of MRSA will assist in controlling
      its dissemination.

PMID- 21901874
TI  - Study of infection by Rickettsiae of the spotted fever group in humans and ticks
      in an urban park located in the City of Londrina, State of Parana, Brazil.
AB  - INTRODUCTION: Spotted fevers are emerging zoonoses caused by Rickettsia species
      in the spotted fever group (SFG). Rickettsia rickettsii is the main etiologic
      agent of Brazilian spotted fever (BSF)and it is transmitted by Amblyomma spp.
      ticks. METHODS: The study aimed to investigate SFG rickettsiae in the Arthur
      Thomas Municipal Park in Londrina, PR, by collecting free-living ticks and ticks
      from capybaras and blood samples from personnel working in these areas. Samples
      from A. dubitatum and A. cajennense were submitted for PCR in pools to analyze
      the Rickettsia spp. gltA (citrate synthase gene). RESULTS: All the pools analyzed
      were negative. Human sera were tested by indirect immunofluorescence assay with
      R. rickettsii and R. parkeri as antigens.Among the 34 sera analyzed, seven
      (20.6%) were reactive for R. rickettsii: four of these had endpoint titers equal
      to 64, 2 titers were 128 and 1 titer was 256. None of the samples were reactive
      for R. parkeri. An epidemiological questionnaire was applied to the park staff,
      but no statistically significant associations were identified. CONCLUSIONS: The
      serological studies suggest the presence of Rickettsiae related to SFG that could
      be infecting the human population studied; however, analysis of the ticks
      collected was unable to determine which species maybe involved in transmission to
      humans.

PMID- 21901875
TI  - In vitro differential activity of phospholipases and acid proteinases of clinical
      isolates of Candida.
AB  - INTRODUCTION: Candida yeasts are commensals; however, if the balance of normal
      flora is disrupted or the immune defenses are compromised, Candida species can
      cause disease manifestations. Several attributes contribute to the virulence and
      pathogenicity of Candida, including the production of extracellular hydrolytic
      enzymes, particularly phospholipase and proteinase. This study aimed to
      investigate the in vitro activity of phospholipases and acid proteinases in
      clinical isolates of Candida spp. METHODS: Eighty-two isolates from hospitalized
      patients collected from various sites of origin were analyzed. Phospholipase
      production was performed in egg yolk medium and the production of proteinase was
      verified in a medium containing bovine serum albumin. The study was performed in
      triplicate. RESULTS: Fifty-six (68.3%) of isolates tested were phospholipase
      positive and 16 (44.4%) were positive for proteinase activity. C. tropicalis was
      the species with the highest number of positive isolates for phospholipase
      (91.7%). Statistically significant differences were observed in relation to
      production of phospholipases among species(p<0,0001) and among the strains from
      different sites of origin (p=0.014). Regarding the production of acid protease,
      the isolates of C. parapsilosis tested presented a larger number of producers
      (69.2%). Among the species analyzed, the percentage of protease producing
      isolates did not differ statistically (chi2=1.9 p=0.5901 (chi2=1.9 p=0.5901).
      CONCLUSIONS: The majority of C. non-albicans and all C. albicans isolates were
      great producers of hydrolytic enzymes and,consequently, might be able to cause
      infection under favorable conditions.

PMID- 21901876
TI  - [On the issue of medical activity of patients of departmental polyclinic].
AB  - The article deals with the analysis of results of the sociologic survey
      concerning the medical activity of patient of departmental polyclinic. The
      patients were investigated about organization of their early additional
      dispanserization and the quality of provided preventive services and needs in
      them.

PMID- 21901877
TI  - [The medical care availability to ophthalmologic patients at various
      organizational and legal forms of its rendering].
AB  - The article deals with the issues of ophthalmologic medical care availability in
      Tverskaya oblast. The comparative analysis is made of activities of medical
      organizations of various forms of property in the field of ophthalmologic care.
      The data of sociologic survey testifies the features of functioning and
      availability of the ophthalmologic care system in Russian region. The data
      permits to elicit the most urgent issues in this area and to determine the
      possible directions of overcoming.

PMID- 21901878
TI  - [The expertise of quality assessment of obstetric-gynecologic and neonatal care
      at different stages of its delivery].
AB  - The results of sociologic survey of obstetrician-gynecologists in various medical
      organizations of Penzenskaya oblast are discussed. The issues of delivering
      medical care to pregnant women, parturient women, gynecologic patients and
      newborns are considered. The expertise is made concerning the quality of
      secondary medical care at every stage of its delivering. The study demonstrated
      that obstetric-gynecologic and neonatal care of higher quality is delivered in
      perinatal center.

PMID- 21901879
TI  - [The medical social care to pregnant women in the municipal maternity welfare
      clinics].
AB  - The article deals with issues of quality of medical social care based on the
      analysis of expertise of 565 individual records of pregnant women four municipal
      maternity welfare clinics of Makhachkala of the Republic of Dagestan. The
      significant shortcomings were established. In 25.9% the pregnant women were
      examined incompletely. The standards of pregnant women monitoring are not
      implemented. The pre-delivery home nursing was not carried out in 15.3% and large
      part of pregnant women was not registered timely. The treatment of pregnant women
      with extra-genital diseases in 22.1% was applied untimely and in 14.4% was
      inadequate. The guidelines were developed to enhance the quality of medical
      social care to pregnant women.

PMID- 21901880
TI  - [The principles of oncologic medical care provided to workers of mining and
      smelting complex in city of Navoi].
AB  - The article deals with the main results of study of morbidity, prevalence and
      mortality of population in Navoi oblast of the Republic of Uzbekistan and Navoi
      mining and smelting complex in 1992-2004. It is demonstrated that in Navoi oblast
      the oncologic neoplasm morbidity took one of the first places in the Republic of
      Uzbekistan due to the additional carcinogenic risk factors produced by mining and
      smelting complex. The results of the first stage of the target comprehensive anti
      oncologic program implemented in the mining and smelting complex in city of Navoi
      permitted to elaborate the major directions of improvement of population
      oncologic health, including more healthy and safe workplaces.

PMID- 21901881
TI  - [Resistance to antiplatelet drugs in patients with cerebrovascular disorders].
AB  - This review concerns clinical and laboratory resistance to antiplatelet drugs
      (aspirin and clopidogrel) in patients with cerebrovascular disorders. Results of
      certain clinical trials showed that laboratory resistance to antiaggregants is
      associated with recurrent thromboembolic vascular events. The commonest causes of
      aspirin resistance are production of arachidonic acid metabolites via the
      lipoxygenase pathway, poor compliance with the treatment, polymorphism of the
      genes encoding for cyclooxygenase and glycoprotein (GP) IIb/IIIa, endothelial
      dysfunction. The causes of clopidogrel resistance include inadequate doses of the
      drug, its low absorption, poor compliance with the treatment, polymorphism of ADP
      receptors, GP IIb/IIIa and cytochrome P450 genes, acute coronary syndrome and
      stroke, metabolic syndrome. Therapeutic efficacy of antiaggregants can be
      improved by increasing their doses, using membranotropic agents, correcting
      endothelial dysfunction, etc. Because the apparent variability of antiplatelet
      drug resistance is currently due to the use of different test-systems by
      different authors, the evaluation of individual sensitivity to a given drug
      showing laboratory resistance and the choice of alternative therapy are thus far
      possible only in the framework of clinical studies. Large-scale prospective
      multicenter trials of antiplatelet drug resistance are needed along with research
      for better understanding mechanisms of individual platelet sensitivity and
      resistance to antiaggregants and developing efficacious methods for their
      correction.

PMID- 21901882
TI  - [Topical problems of the modern epidemiology (data for presentation at the all
      Russian scientific conference "The problems of modern epidemiology. Perspective
      means and methods for the laboratory diagnosis and prevention of urgent
      infections")].
AB  - The strategic goal of preserving the nation's health, reducing mortality rates,
      and overcoming the demographic decline has been realized in Russia over the
      recent years. To decrease the incidence of infectious diseases is a substantial
      reserve for reducing mortality rates and increasing lifespan. The Russian
      Federation is augmenting the interaction in the problem of infectious diseases
      within the framework of the Shanghai Cooperation, CIS, EuroAsEC, etc. Our country
      implements hundreds of regional programs on the sanitary-and-epidemiological well
      being of the population every year. Considerable progress has been made in
      reducing the incidence of infections controlled by specific preventive means. It
      is essential to implement a national priority health project on mass additional
      immunization against viral hepatitis B, measles, German measles, influenza, and
      poliomyelitis, and on the prevention and treatment of HIV/AID and viral hepatitis
      B and C.

PMID- 21901883
TI  - [Biological, chemical, and radiation factors in the classification of medical
      waste].
AB  - The current classification of medical waste does not consider the sanitary-and
      chemical hazard of epidemiologically dangerous and extremely dangerous medical
      waste (classes B and C). According to the results of the studies performed, the
      authors propose the improved classification of medical waste, which makes it
      possible to take into account not only infectious, radiation, and toxicological,
      but also sanitary-and-chemical hazards (toxicity, carcinogenicity, mutagenicity,
      and biological activity) of medical waste.

PMID- 21901884
TI  - [Morbidity among senior preschool children in Magnitogorsk].
AB  - The publication is the third fragment of the multiparameter study. The level and
      causes of genome instability and sensitivity are assessed in children living in
      Magnitogorsk, a city with one of the largest mills in Russia. The city is in the
      list of the world's 35 most polluted ones. A transverse retrospective analysis
      found no differences in primary morbidity among 5-7-year-old children who had
      been living in different districts of Magnitogorsk since birth and were going to
      municipal kindergartens located adjacent to their house. Contrary to the
      expectations, the prevalence of morbidity and diseases that were markers for an
      industrial town was significantly lower among the children residing in the
      settlements situated around the mills than that in the city's other districts.
      There were 9 organic compounds that had no hygienic standards, the content of
      which in the snow samples collected in the areas of the examined kindergartens
      correlated with the prevalence of the children's morbidity. Family social and
      living conditions were shown to affect the children's morbidity.

PMID- 21901885
TI  - [Biosphere as a working space -- unity and the opposite].
AB  - The paper gives examples of contradictions between the human working activities
      and the work space and environment, which leads to disharmony in their relations
      and calls for human considered decisions to prevent its anthropogenic impact on
      the environment.

PMID- 21901886
TI  - [The characteristics of morphofunctional status of rural schoolchildren].
AB  - The authors made a complex evaluation of the physical development of 7-16-year
      old rural schoolchildren from a large administrative territorial entity and
      developed age-gender-related standards, by using the percentile technique. There
      were significant morphofunctional differences between the urban and rural
      schoolchildren at the present stage of a secular trend, which determines the
      necessity of developing the physical development standards for rural children and
      adolescents in order to correctly interpret the data on their health status.

PMID- 21901887
TI  - [Determination of phthalic anhydride in ambient air by high performance liquid
      chromatography].
AB  - The paper considers the measurement of phthalic anhydride in the ambient air
      samples by high performance liquid chromatography. It describes conditions for
      air sampling and analysis of phthalic anhydride levels in the presence of
      concomitant components of its production (phthalic and maleic acids, maleic
      anhydride, etc.) on a liquid chromatograph with an UV detector. The procedure was
      tested, by estimating the quality of ambient air at the border of a sanitary
      protection zone of phthalic anhydride production and when analyzing the air in
      the industrial area. Field studies detected the concentrations of phthalic
      anhydrate in the air of an enterprise area, which were equal to 0.017-0.115
      mg/dm3. Phthalic anhydride was detectable at a concentration of 0.001-0.0021
      mg/dm3 at the border of the existing sanitary protection zone in single cases.
      The procedure has been recommended to measure the mass concentrations of phthalic
      anhydride aerosol and vapors in ambient air at the reference concentration.

PMID- 21901888
TI  - [Professor V. A. Arnol'dov--a hygienist, scientist, university teacher, and
      initiator of sanitation in Russia (on his 150th birthday)].
AB  - The paper gives Professor V. A. Arnoldov's brief bibliographic data pertaining to
      the development of sanitation and zemstvo medicine in Bashkiria, Tatarstan, and
      the Saratov Province. It shows V. A. Arnoldov's scientific and pedagogical
      potential in the development of preventive medicine in Russia.

PMID- 21901889
TI  - [The pericytes, endothelium monolayer, collagen and elastin chains as the
      elements of areolar tissue and the substrates of chemical reaction of
      glyserization].
AB  - The microangiopathy under hyperglycemia and diabetes develops only in the
      microcirculation component of circulatory system. In this area considerable
      amount of pericytes is concentrated. These cells contain myofibrils and in
      circulatory mode envelop capillaries being situated on the outside of basilemma.
      It is possible that in a phylogenetic sense this is the earliest functional unity
      of endothelium monolayer as a pacemaker and pericytes as contractile elements
      which are the earliest "propeller" because of implementing the function of
      advancement of lymph, hemolymph and blood in capillaries. Probably, endothelium
      and pericytes formed the first variation of peristaltic "pump" for the purpose of
      blood advancement longwise of capillaries. Most probably, the state of distal
      part of arterial race (muscular type arterioles) impact the parameters of
      proximal part of arterial race (elastic type arterioles) and myocardium itself in
      the same extent as the state of "pump" in capillaries, endothelium and pericytes
      function impact the function of local peristaltic pumps (muscular type
      arterioles) in paracrine cenosis. It is supposed that the pericytes are the
      regulators of physical, hydraulic factor of activation of biologic reaction of
      transcitosis--excretion of nutrients and humoral mediators from capillaries to
      the pool of intercellular medium to perform the biologic function of homeostasis.
      Hyperglycemia, glycotoxins formation, bivalent substances (glyoxal,
      methilglyoxal, malonic dialdehyde) reacting simultaneously by both ends of
      molecule result in formation within collagen of areolar tissue of short
      transversal cross-links (glycosylation end product) which significantly increase
      rigidity (hardness) of capillary wall. In these conditions, myofibrils of
      pericytes no longer form directed deformation of capillary wall to effect
      peristalsis and advancement of hemolymph (blood later on) along capillaries
      according the synthesis of monolayer endothelium NO as a dilatation factor. This
      is the cause of blood circulation disturbance on the level of exchange
      capillaries and formation of chronic hypoxemia resulting in the only increase of
      rate of glycosylation chemical reaction. The microangiopathy is formed in the
      cells and tissues in an integrated pool of intercellular medium and never occurs
      in the cerebrospinal fluid pool where no hyperglycemia develops.

PMID- 21901890
TI  - [The detection of oxidation-modified lipoproteins and their antibodies in case of
      complicated course of myocardial infarction with segment ST boost].
AB  - According contemporary conceptions, the key role in the development of
      atherosclerosis play the low density oxidative modified lipoproteins and its
      antibodies. The purpose of the study was to discover the characteristics of
      changes in lipid metabolism indicators, including the low density oxidative
      modified lipoproteins and their antibodies. The factors of oxidative status in
      patients with cardiac infarction with complicated and non-complicated course were
      considered. It is established that the development of cardiac infarction is
      followed the increase of concentration of low density oxidative modified
      lipoproteins and their antibodies both during the first day after acute pain
      syndrome and stabilization period. The evaluation of content of low density
      oxidative modified lipoproteins and their antibodies broaden the possibilities of
      diagnostics, prognosis and decrease of risk of development both acute and
      recurrent coronary events.

PMID- 21901891
TI  - [The laboratory evidences of chronic disease impact on the development of anemia
      under female reproductive system pathology].
AB  - The study sample included 170 patients with gynecological diseases, 5 patients
      with persistent anemia due to systematic blood disorder, 14 healthy patients. The
      decrease of hemoglobin level lower than 110 g/l is established in 25.7%
      gynecologic patients and most frequently in those with hysteromyoma. The study
      revealed that anemia developed due to the female reproductive system disorders
      and independently of clinically marked loss of blood is an. The biologic
      characteristic of anemia is the decrease of erythrocytes production under certain
      diseases against the background of inadequate production of endogenic
      erythropoietin. The effectiveness of treatment of iron-deficiency anemia is less
      under decrease of amount of erythrokaryocytes in bone marrow.

PMID- 21901892
TI  - [The aggregation capacity of thrombocytes, lymphocytic thrombocytic adhesion and
      content of D-dimers in patients with acute acetic acid intoxication].
AB  - In patients with acute acetic acid intoxication the diminution of degree and
      velocity of thrombocytes aggregation against the background of their amount
      attenuation in peripheral blood is established. The significant augmentation of
      amount of lymphocytic thrombocytic complexes and -dimers concentration in blood
      is revealed. The most marked alterations are determined on first and second days
      in patients with severe degree of intoxication.

PMID- 21901893
TI  - [The new approach in diagnostics of systemic lupus erythematosus: the
      immunoagglutination of collaurin].
AB  - The data is presented concerning the implementation of nano-particles of aurum in
      the diagnostics of systemic lupus erythematosus. It is demonstrated that nano
      particles sensibilized by deoxyribonucleoprotein are able to detect the specific
      antibodies--the known markers of systemic lupus erythematosus. To optimize the
      reaction various approaches were applied. The comparative analysis was made
      including latex-agglutination technique, immune-enzyme analysis and fluorescence
      immunoassay. It is demonstrated that the given system is characterized by very
      high sensibility to determine the specific antibodies and hence can be
      effectively applied in diagnostics process.

PMID- 21901894
TI  - [Do not let go of our values as caregivers].

PMID- 21901895
TI  - [The Alzheimer Plan, three years since implementation].

PMID- 21901896
TI  - [Heart valve diseases, from physiology to diagnosis].

PMID- 21901897
TI  - [Has the World Health Organization lost its independence, its relevance, is it
      too inefficient? ].

PMID- 21901898
TI  - Bromeliad population genetics reveals species cohesion against the odds.

PMID- 21901899
TI  - Women, microcredit and family planning practices: a case study from rural Ghana.
AB  - This paper examines the influence of informal banking club participation on
      family planning practices in rural Ghana. Research from Asia suggests that family
      planning practices are improved by club participation. This study examines this
      thesis in an African context, using rural Ghana as a case study. A sample of 204
      women (19 years and older) was drawn from Abokobi village, Ghana. Multivariate
      analyses of direct, mediating and moderating effects of women's demographic
      background characteristics, membership status and length, and women's empowerment
      status as predictors of family planning practices are assessed. Findings suggest
      that club membership and membership length is not associated with family planning
      practices; however, age, education level, number of children and empowerment
      status are.

PMID- 21901901
TI  - "What we need is a crop ecologist": ecology and agricultural science in
      Progressive-era America.
AB  - Though they are often seen as foils for each other, ecology and agricultural
      science co-evolved. With shared roots in late nineteenth-century botany,
      ecologists and agronomists fostered important connections during the Progressive
      era that have been largely overlooked despite a number of finely nuanced studies
      of ecology's origins. But if 'applied ecology' once effectively meant
      agriculture, over the course of the first decades of the twentieth century the
      relationship between ecology and scientific agriculture grew strained.
      Agriculturists narrowed their focus to increasing yields, and ecologists sought
      to establish their discipline as a distant theoretical science and so distanced
      themselves from its agricultural applications. By the end of World War I, the
      process of disciplinary specialization was well underway. In time, the two
      disciplines diverged so completely that the once vital connections between them
      were obscured and forgotten.

PMID- 21901902
TI  - Nectar for the taking: the popularization of scientific bee culture in England,
      1609-1809.
AB  - This essay expands and refines academic knowledge of English beekeeping during
      the seventeenth and eighteenth centuries. Scientific beekeeping focused on
      improvement, which, in turn, depended on the dissemination of ideas and
      practices. This analysis, therefore, encompasses the mentalities and tactics of
      popularizers. The article also identifies two neglected concepts in the
      popularization campaign. First, popularizers saw scientific beekeeping as a way
      to end the tradition of killing the bees in order to safely harvest. Second, they
      sought to promote a rural industry for the economic welfare of the nation. The
      case study of Exeter's Western Apiarian Society reveals precisely how
      popularization functioned in reality. The result is a more thorough history of
      scientific beekeeping and how the rhetoric of improvement related to the culture
      of practice.

PMID- 21901903
TI  - Colonialism, planters, sugarcane, and the agrarian economy of Caguas, Puerto
      Rico, between the 1890s and 1930.
AB  - This article presents new research on the impact and consequences of the
      incorporation of Puerto Rico into the American economic sphere of influence and
      how much change truly took place during the first decades of the twentieth
      century. As reconstructed here, Puerto Rico's social and economic structure did
      change after the American invasion. However, a closer look at the data reveals
      that, contrary to the generally accepted conclusions, land tenure did not become
      concentrated in fewer hands. Puerto Rico did experience profound changes with the
      rapid growth of US agribusiness and the penetration of American capital. In the
      process of arriving on the island, these two interests found a land tenure system
      in the firm control of local farmers (small, medium, and large). The American
      invasion and subsequent incorporation of the island into the American
      economic/political system as a non-incorporated territory provided the conditions
      for the numerical increase of farms and farmers in the island during the first
      three decades of the twentieth century.

PMID- 21901904
TI  - Academic freedom or political maneuvers: Theodore W. Schultz and the
      oleomargarine controversy revisited.
AB  - The oleomargarine controversy was a case of academic freedom in which nineteen
      researchers resigned from Iowa State College to protest pressure from the dairy
      industry to change their research findings. This article explores the ways in
      which the boundaries between science and politics were more blurred than they
      seemed at the time or in subsequent historical treatments. The argument begins
      with a history of the unique composition of agricultural economics research at
      Iowa State, refocuses the affair from a conflict between the state college and
      the dairy industry to one among a much larger number of actors, and concludes by
      demonstrating that one professor, Theodore Schultz, was in the process of
      transitioning to a new career in prescriptive policy work with private policy
      associations that ended up being opposed to the practices and policy goals of
      some of the farm organizations in question.

PMID- 21901905
TI  - Wave of mutilation: the cattle mutilation phenomenon of the 1970s.
AB  - During the 1970s many small-scale cattle ranchers across the Midwest reported
      finding their cattle mutilated. The episode, often dismissed as mass hysteria or
      sensationalized reporting, demonstrates the growing dissatisfaction of many
      ranchers concerning government intrusiveness and restrictive policies. These
      frustrations found a release in response to the mutilation phenomenon during
      which ranchers vented their anger by taking direct aim at the federal government.
      The turbulent economic conditions of the period paired with government
      interference in the cattle industry helped sustain the mutilation phenomenon as
      ranchers projected their fears and insecurities through the bizarre episode. The
      hostility ranchers showed toward the federal government during the mutilation
      scare presaged and helped provide the impetus for events such as the Sagebrush
      Rebellion. The mutilation phenomenon also underscores the pronounced effects of
      the libertarian movement of the 1960s that gave rise to the New Right and gained
      adherents across the West and Midwest.

PMID- 21901906
TI  - Protection against rotavirus challenge in mice orally inoculated with trypsin
      inhibitor.
AB  - BACKGROUND AND OBJECTIVES: the burden of rotavirus disease is significant in
      developed as well as developing countries and has not diminished with improved
      hygiene. In the present studies the protective efficacy of soyabean trypsin
      inhibitor (TI) was investigated on the gut following rotavirus (RV) infection in
      inbred mice. METHODS: infant BALB/c mice of 7 days age (n=108) were divided into
      three equal groups (control, RV and RV+TI). Animals were orally inoculated either
      with normal saline, EB RV (serotype-3) or RV+TI and were sacrificed under light
      chloroform anesthesia on days 0, 1, 3, 5, 7 and 10 post inoculation (pi). Gamma
      glutamyl transpeptidase (GGT), leucine aminopeptidase (LAP), and leucine amino
      acid uptake in the jejunum and ileum were assessed. RESULTS: rotavirus inoculated
      animals showed significant reduction in body weights on days 3 and 5 pi as a
      result of diarrhoea which resolved by day 7 pi. In RV+TI inoculated animals
      diarrhoea jejunum and ileum in mice inoculated with RV as compared to controls.
      With the administration of TI the amino acid uptake, and GGT and LAP levels were
      higher in both segments of the small intestine and comparable to the controls.
      INTERPRETATION AND CONCLUSIONS: on the administration of TI, leucine amino acid
      uptake, and levels of GGT and LAP were similar to the controls in the jejunum and
      ileum of infant mice showing its possible protective efficacy during rotavirus
      infection.

PMID- 21901907
TI  - Impact of vitamin A supplementation to rural children on morbidity due to
      diarrhoea.
AB  - BACKGROUND AND OBJECTIVES: a number of studies have shown the association between
      vitamin A deficiency and the increased risk of diarrhoeal and other childhood
      morbidities and mortality. However, some studies have raised controversies
      regarding the reduction of the incidence of diarrhoea after vitamin A
      supplementation to children. This study was undertaken to evaluate the
      effectiveness of vitamin A supplementation to young rural children in reducing
      the incidence of diarrhoea. METHODS: a double-blind randomized intervention trial
      was carried out amongst 404 rural children between 6-59 months of age to assess
      the impact of vitamin A supplementation on morbidity due to diarrhoea. Children
      aged 6-59 months were enrolled and allocated to receive either 200,000 or 50,000
      IU of vitamin A and the same dose was repeated after six months. Morbidity due to
      diarrhoea was observed by twice-a-week household surveillance, during the
      subsequent one year of follow up. The incidence of diarrhoea was compared between
      the two supplemented groups. In addition, the overall incidence of diarrhoea n
      the two supplemented groups was also compared with the incidence observed during
      the year preceding supplementation. RESULTS: the incidence of diarrhoea was
      similar in the two supplemented groups (Incidence Rate Ratio = 1.05. 95% C. I.
      0.79-1.40). However, the overall incidence of diarrhoea among all the children in
      the two supplemented groups (0.56 episodes/child/year) was significantly lower
      than the incidence before supplementation (1.15 episodes/child/year). The
      Incidence Rate Ratio was 0.49 with 95% C.I 0.40-0.59. INTERPRETATION AND
      CONCLUSIONS: the results of this study indicate that vitamin A supplementation in
      a dose of 200,000 IU, has no additional advantage over 50,000 IU, at least when
      the aim is to reduce the incidence of diarrhoea. For control of morbidity due to
      diarrhoea, vitamin A supplementation in a dose of 50,000 IU every six months
      appears to be adequate, cost effective and suitable for younger children.

PMID- 21901908
TI  - Glomerular injury induced in mice by intraperitoneal injection of Shiga-like
      toxins.
AB  - BACKGROUND AND OBJECTIVES: Shiga-like toxins I and II (Stx1 and Stx2) play an
      important role in the pathogenesis of renal disease by causing renal
      microvascular injury. A murine model was used to study glomerular lesions
      produced by Stx1 and Stx2. METHODS: Swiss albino mice of the Rockefeller strain
      were inoculated intraperitoneally with LD(50) doses of endotoxin-free Stx1 of
      Stx2 and observed for signs of disease. Samples of renal cortical tissue from
      mice were examined with the electron microscope. RESULTS: the mice developed
      systemic and neurological symptoms including hind limb paralysis and generalised
      convulsions. Renal arteriolar damage and glomerular endothelial cytoplasmic
      swelling, vacuolation, lysis and intravascular coagulation were present and
      resembled the microangiopathy seen in renal biopsies from patients.
      INTERPRETATION AND CONCLUSIONS: these experiments establish the role of Stx1 and
      Stx2 in glomerular vascular injury and provide a model for studying the
      pathogenesis of Shiga-like toxin related microangiopathy.

PMID- 21901909
TI  - Tar Heel footprints in health care: Denise Levis Hewson, BSN, RN, MSPH.

PMID- 21901910
TI  - Use of data by hospitals in North Carolina to identify disparities in the care
      and outcomes of minority patients.
AB  - BACKGROUND: Hospitals are now called upon to use available data--information on
      the use of services, patient satisfaction, and core quality measures--to identify
      disparities in the use and outcomes of services for minority patients. This study
      assesses whether and in what ways hospitals in North Carolina use data to
      understand the experiences of minority patients. METHODS: Semistructured
      telephone interviews were completed with chief executive officers (CEOs) and
      other administrators from a broad sample of North Carolina hospitals.
      Participants were asked about their hospitals' use of data to compare experiences
      of minority and nonminority patients and about any other minority-focused
      initiatives. Responses were analyzed using a grounded theory approach. RESULTS: A
      total of 28 CEOs and administrators from 17 (77%) of 22 targeted hospitals
      participated fully in the interviews. Participating hospitals ranged in size from
      fewer than 60 beds to more than 700 beds and were equally distributed across the
      state's 3 geographic regions. Three hospitals (18%) reportedly analyzed data by
      patient race to assess satisfaction, specific clinical outcomes, adverse events,
      and/or use of services. Respondents cited barriers to analyzing hospital data by
      patient race and ethnicity as lack of resources, not knowing how to perform these
      analyses, and not seeing the need. Respondents for 10 hospitals (59%) reported
      other types of hospital programs targeting the needs of minority patients,
      including cultural-sensitivity training for staff and initiatives in local
      communities. LIMITATIONS: Participating hospitals may not reflect all North
      Carolina hospitals in their minority-focused efforts, and respondents may not
      have known about all relevant programs in their hospitals. CONCLUSIONS: Few
      hospitals in North Carolina are proactively identifying disparities between
      minority and nonminority patients by use of data.

PMID- 21901911
TI  - Knowledge and perceptions among overweight and obese employees about lifestyle
      related health benefit changes.
AB  - BACKGROUND: We investigated perceptions among overweight and obese state
      employees about changes to health insurance that were designed to reduce the
      scope of health benefits for employees who are obese or who smoke. METHODS:
      Before implementation of health benefit plan changes, 658 state employees who
      were overweight (ie, those with a body mass index [BMI] of 25-29.9) or obese (ie,
      those with a BMI of > or = 30) enrolled in a weight-loss intervention study were
      asked about their attitudes and beliefs concerning the new benefit plan changes.
      RESULTS: Thirty-one percent of employees with a measured BMI of 40 or greater
      self-reported a BMI of less than 40, suggesting they were unaware that their
      current BMI would place them in a higher-risk benefit plan. More than half of all
      respondents reported that the new benefit changes would motivate them to make
      behavioral changes, but fewer than half felt confident in their ability to make
      changes. Respondents with a BMI of 40 or greater were more likely than
      respondents in lower BMI categories to oppose the new changes focused on obesity
      (P < .001). Current smokers were more likely than former smokers and nonsmokers
      to oppose the new benefit changes focused on tobacco use (P < .01). LIMITATIONS:
      Participants represented a sample of employees enrolled in a weight-loss study,
      limiting generalizability to the larger population of state employees.
      CONCLUSIONS: Benefit plan changes that require employees who are obese and smoke
      to pay more for health care may motivate some, but not all, individuals to change
      their behaviors. Since confidence to lose weight was lowest among individuals in
      the highest BMI categories, more-intense intervention options may be needed to
      achieve desired health behavior changes.

PMID- 21901912
TI  - A qualitative analysis of career transitions made by internal medicine-pediatrics
      residency training graduates.
AB  - BACKGROUND: Physicians who complete combined residency training in internal
      medicine and pediatrics (med-peds) have a variety of career options after
      training. Little is known about career transitions among this group or among
      other broadly trained physicians. METHODS: To better understand these career
      transitions, we conducted semistructured, in-depth, telephone interviews of
      graduates of the University of North Carolina-Chapel Hill School of Medicine med
      peds program who self-identified as having had a career transition since
      completing training. We qualitatively analyzed interview transcripts, to develop
      themes describing their career transitions. RESULTS: Of 106 physicians who
      graduated during 1980-2007, 20 participated in interviews. Participants
      identified factors such as personality, work environment, lifestyle, family, and
      finances as important to career transition. Five other themes emerged from the
      data; the following 4 were confirmed by follow-up interviews: (1) experiences
      during residency were not sufficient to predict future job satisfaction; work
      after the completion of training was necessary to discover career preferences;
      (2) a major factor motivating job change was a perceived lack of control in the
      workplace; (3) participants described a sense of regret if they did not continue
      to see both adult and pediatric patients as a result of their career change; (4)
      participants appreciated their broad training and, regardless of career path,
      would choose to pursue combined residency training again. LIMITATIONS: We
      included only a small number of graduates from a single institution. We did not
      interview graduates who had no career transitions after training. CONCLUSIONS:
      There are many professional opportunities for physicians trained in med-peds.
      Four consistent themes surfaced during interviews about med-peds career
      transitions. Future research should explore how to use these themes to help
      physicians make career choices and employers retain physicians.

PMID- 21901913
TI  - New models of care. Introduction.

PMID- 21901914
TI  - New models of health care payment and delivery.

PMID- 21901915
TI  - Use of the Triple Aim to improve population health.
AB  - CaroMont Health has embraced the Triple Aim initiative to implement its core
      vision and competencies of delivering health care, promoting individual wellness,
      and creating vibrant communities. An imperative to achieve success has been
      aligning the corporate goals with the processes and outcomes that foster the
      Triple Aim.

PMID- 21901916
TI  - Just for Us: in-home care for frail elderly and disabled individuals with low
      incomes.
AB  - In response to increasing concerns about health care access, cost, and quality,
      Duke University Medical Center began a community-engaged, iterative, data-driven
      process in 1998 to develop innovative models to provide care earlier, more
      effectively, and at a lower cost. This commentary reviews Just for Us, an in-home
      care program launched in 2002 for low-income, frail elderly and disabled
      individuals.

PMID- 21901917
TI  - Linking primary care with adult care homes.
AB  - This commentary describes a pilot program wherein a community health center is
      partnering with Community Care of North Carolina to create a system of integrated
      care management and "treatment-in-place" visits for aged residents and disabled
      residents of adult care homes, with the goal of improving the quality of care and
      reducing unnecessary visits to emergency departments.

PMID- 21901918
TI  - The PACE program: home-based care for nursing home-eligible individuals.
AB  - The Program for All-Inclusive Care of the Elderly (PACE) is a Medicare/Medicaid
      managed care benefit for frail adults aged 55 years and older who, although
      certified by the state as nursing home eligible, choose to live in the community.
      The PACE model features comprehensive medical and social services coordinated by
      an interdisciplinary team whose goal is to promote independence and quality of
      life.

PMID- 21901919
TI  - Redesigning the rural health center: high tech, high touch, and low overhead.
AB  - To attract new physicians to rural primary care, new models of care are needed
      that are more effective, more sustainable, and replicable in smaller communities.
      This commentary provides a brief description of preliminary findings associated
      with a radically redesigned, low-overhead patient-centered medical-home practice
      model in North Carolina.

PMID- 21901920
TI  - Use of telehealth to improve chronic disease management.
AB  - Remote patient monitoring that tracks vital signs of patients with chronic
      diseases is offering more-frequent contact between the patient and the primary
      care provider, providing earlier detection of potential problems, and allowing
      real-time alerts, resulting in a proactive, affordable option for best-practice
      health care.

PMID- 21901921
TI  - Use of telepsychiatry to improve care for people with mental illness in rural
      North Carolina.
AB  - Telehealth improves access to medical services, especially for people living in
      rural areas. In North Carolina, the advantages of telepsychiatry also go beyond
      improving access. This article describes a diverse program of telehealth and
      telepsychiatric service delivery and discusses its advantages and disadvantages.

PMID- 21901922
TI  - UNC Health Systems and Blue Cross and Blue Shield of North Carolina patient
      centered medical home collaborative.
AB  - UNC Health Systems and Blue Cross and Blue Shield of North Carolina have entered
      into a joint venture that is designed to improve patient outcomes and experience
      and to control medical costs for patients with chronic conditions. This
      commentary reviews the impetus for, and the anticipated outcomes of, the model
      practice.

PMID- 21901923
TI  - An update on Community Care of North Carolina's Medicare demonstrations.
AB  - To enhance the impact of Community Care of North Carolina (CCNC)'s population
      health initiatives, CCNC partnered with the US Centers for Medicare and Medicaid
      Services to bring persons who are dually eligible for both Medicaid and Medicare,
      as well as Medicare beneficiaries, into CCNC's system of medical homes and
      community-based care management supports.

PMID- 21901924
TI  - Palliative care and the search for value in health reform.
AB  - Improving value in health care is of paramount importance, and doing so will
      require focus on both the costs and benefits of care. Palliative care addresses
      symptoms of disease regardless of prognosis, helps patients clarify their goals
      of care, and is key in improving value in the health care system.

PMID- 21901925
TI  - The Pregnancy Medical Home: use of the power of the Medicaid program to improve
      the standard of care across North Carolina.
AB  - The Pregnancy Medical Home (PMH) is a value-added, quality metrics-driven
      clinical program to improve the perinatal outcomes for pregnant women across the
      state of North Carolina. The PMH uses modest financial incentives to improve
      access to care, in a team approach led by obstetricians and supported by
      integrated aggressive care and case management.

PMID- 21901926
TI  - Use of health information to improve care: the Southern Piedmont Beacon Community
      Grant.
AB  - In 2009, the Office of the National Coordinator for Health Information Technology
      solicited proposals to participate in the Beacon Community Program. The program
      is designed to support communities with established reputations for adopting
      health information technology solutions. This commentary reviews Community Care
      of Southern Piedmont, a Beacon Community Program in North Carolina.

PMID- 21901927
TI  - Regional extension coordinators: use of practice support and electronic health
      records to improve quality and efficiency.
AB  - The North Carolina Regional Extension Center for Health Information Technology
      provides onsite consultation to primary care practices to help them implement
      electronic health records then use these systems to optimize care through
      measurement, rapid cycle quality improvement, and application of medical home
      functionalities. Services are available from all 9 regional North Carolina Area
      Health Education Centers.

PMID- 21901928
TI  - Proximity to National Committee for Quality Assurance Diabetes Recognition
      Programs among North Carolinians with diabetes.

PMID- 21901929
TI  - Integrating substance abuse treatment into the medical home.

PMID- 21901930
TI  - North Carolina surgical workforce trends.
AB  - Between 1997 and 2008, the number of general surgeons in North Carolina increased
      and shifted demographically, geographically, and by specialty. However, surgeon
      numbers--overall and by specialty--do not appear to have increased as quickly or
      to have shifted in the same ways as North Carolina's general population.

PMID- 21901931
TI  - The evaluation of traditional and early driver training with simulated accident
      scenarios.
AB  - OBJECTIVE: We assessed the driving skills of novice traditionally trained, novice
      early-trained, and experienced drivers to evaluate whether supervised early
      training could improve young drivers' skills. BACKGROUND: The overall
      representation of young male drivers in car crashes is a recurrent problem in
      developed countries.To prevent this overrepresentation, France institutes an
      early driver training program from the age of 16 with the supervision of an
      adult. However, evidence of the positive effects of this system is still lacking.
      METHOD: Three groups of drivers (12 participants each) were confronted with five
      prototypical accident scenarios introduced in a simulated urban circuit. Drivers'
      response time, speed, and vehicle position in the lane were analyzed. RESULTS: No
      difference was detected across groups regarding obstacle detection, as revealed
      by the analysis of response times. But in some unexpected scenarios, position
      control by traditionally trained drivers was more conservative than for more
      experienced drivers, and early-trained drivers were far more likely to respond
      with efficient evasive action. CONCLUSION: The exposure gained by an early
      training program could thus increase the development of visuomotor coordination
      and involve better skills in challenging situations. APPLICATION: The
      supplementary driving experience gained with the supervision of an adult during
      early training could promote the skills necessary to deal with risky situations.
      Driving simulators could be used to confront young drivers with a broad range of
      hazardous scenarios not commonly encountered in natural driving.

PMID- 21901932
TI  - Beyond identity: incorporating system reliability information into an automated
      combat identification system.
AB  - OBJECTIVE: The aim of this study was to evaluate display formats for an automated
      combat identification (CID) aid. BACKGROUND: Verbally informing users of
      automation reliability improves reliance on automated CID systems. A display can
      provide reliability information in real time. METHOD: We developed and tested
      four visual displays that showed both target identity and system reliability
      information. Display type (pie, random mesh) and display proximity (integrated,
      separated) of identity and reliability information were manipulated. In
      Experiment 1, participants used the displays while engaging targets in a
      simulated combat environment. In Experiment 2, participants briefly viewed still
      scenes from the simulation. RESULTS: Participants relied on the automation more
      appropriately with the integrated display than with the separated display.
      Participants using the random mesh display showed greater sensitivity than those
      using a pie chart. However, in Experiment 2, the sensitivity effects were limited
      to lower reliability levels. CONCLUSION: The integrated display format and the
      random mesh display were the most effective displays tested. APPLICATION: We
      recommend the use of the integrated format and a random mesh display to indicate
      identity and reliability information with an automated CID system.

PMID- 21901933
TI  - Affective processes in human-automation interactions.
AB  - OBJECTIVE: This study contributes to the literature on automation reliance by
      illuminating the influences of user moods and emotions on reliance on automated
      systems. BACKGROUND: Past work has focused predominantly on cognitive and
      attitudinal variables, such as perceived machine reliability and trust. However,
      recent work on human decision making suggests that affective variables (i.e.,
      moods and emotions) are also important. Drawing from the affect infusion model,
      significant effects of affect are hypothesized. Furthermore, a new affectively
      laden attitude termed liking is introduced. METHOD: Participants watched video
      clips selected to induce positive or negative moods, then interacted with a
      fictitious automated system on an X-ray screening task At five time points,
      important variables were assessed including trust, liking, perceived machine
      accuracy, user self-perceived accuracy, and reliance.These variables, along with
      propensity to trust machines and state affect, were integrated in a structural
      equation model. RESULTS: Happiness significantly increased trust and liking for
      the system throughout the task. Liking was the only variable that significantly
      predicted reliance early in the task. Trust predicted reliance later in the task,
      whereas perceived machine accuracy and user self-perceived accuracy had no
      significant direct effects on reliance at any time. CONCLUSION: Affective
      influences on automation reliance are demonstrated, suggesting that this decision
      making process may be less rational and more emotional than previously
      acknowledged. APPLICATION: Liking for a new system may be key to appropriate
      reliance, particularly early in the task. Positive affect can be easily induced
      and may be a lever for increasing liking.

PMID- 21901934
TI  - The validity and interrater reliability of video-based posture observation during
      asymmetric lifting tasks.
AB  - OBJECTIVE: The objective was to evaluate the validity and interrater reliability
      of a video-based posture observation method for the major body segment angles
      during asymmetric lifting tasks. BACKGROUND: Observational methods have been
      widely used as an awkward-posture assessment tool for ergonomics studies.
      Previous research proposed a video-based posture observation method with
      estimation of major segment angles during lifting tasks. However, it was limited
      to symmetric lifting tasks. The current study extended this method to asymmetric
      lifting tasks and investigated the validity and the interrater reliability.
      METHOD: Various asymmetric lifting tasks were performed in a laboratory while a
      side-view video camera recorded the lift, and the body segment angles were
      measured directly by a motion tracking system. For this study, 10 raters
      estimated seven major segment angles using a customized program that played back
      the video recording, thus allowing users to enter segment angles. The validity of
      estimated segment angles was evaluated in relation to measured segment angles.
      Interrater reliability was assessed among the raters. RESULTS: For all the
      segment angles except trunk lateral bending, the estimated segment angles were
      strongly correlated with the measured segment angles (r > .8), and the intraclass
      correlation coefficient was greater than 0.75. CONCLUSION: The proposed
      observational method was able to provide a robust estimation of major segment
      angles for asymmetric lifting tasks based on side-view video clips. The estimated
      segment angles were consistent among raters. APPLICATION: This method can be used
      for assessing posture during asymmetric lifting tasks. It also supports
      developing a video-based rapid joint loading estimation method.

PMID- 21901936
TI  - Modeling training effects using a human performance taxonomy.
AB  - OBJECTIVE: The aim of this study was to characterize skill acquisition during
      training and skill retention as a function of training strategy, retention
      period, and task type in the form of a numerical model and then apply that model
      to make predictions of performance on an unknown task. BACKGROUND: Complex
      systems require efficient and effective training programs for the humans who
      operate them in discontinuous fashion. Although there are several constructs for
      learning theory, models that enable analysts to predict training outcomes are
      needed during the design of training programs. METHOD: This study involved 60
      participants who were trained on five tasks relevant to RQ-I Predator unmanned
      aircraft system sensor operators by one of three strategies that represented a
      continuum of instructor interactivity. After training, performance data for all
      five tasks were collected. Participants completed the same tasks 30 or 60 days
      later to determine skill retention and the rate at which task proficiency was
      reacquired. RESULTS: Models built from tasks that isolate human performance
      channels adequately predicted performance on a task that combined those channels.
      CONCLUSION: Models that predict performance on tasks that isolate human
      performance channels can be used to make predictions on tasks that draw on
      multiple channels.This model provided a distribution of performance data that was
      statistically similar to actual performance data. APPLICATION: System designers
      trained with human performance data on a set of tasks can apply those tasks'
      characteristics to future tasks to make reasonably accurate performance
      predictions, thereby allowing the designers to make early decisions regarding
      training strategy to teach those tasks.

PMID- 21901935
TI  - Compatibility relationships with simple lever tools.
AB  - OBJECTIVE: The study focuses on potential compatibility relationships when simple
      lever tools are used. BACKGROUND: Spatial compatibility between stimuli and
      responses determines performance. However, many tasks require the use of simple
      tools, such as levers that transform hand movements into tool movements. We
      explore with such a tool whether and how the correspondence or noncorrespondence
      between stimulus-side and hand movement (stimulus-response compatibility),
      between stimulus-side and tool-effect movement (stimulus-effect compatibility),
      and/or between hand movement and tool-effect movement (response-effect
      compatibility) affects performance. METHOD: U-shaped and inverted-U-shaped levers
      were used as tools,allowing us to examine the contribution of each compatibility
      relationship to response times and errors without any confounds and omissions.
      RESULTS: Responding was delayed and error prone when the hand movement and the
      movement of the effect point of the tool did not correspond. Effects of stimulus
      response compatibility and stimulus-effect compatibility were observed only when
      the hand movement direction remained untransformed in the tool-effect movement
      CONCLUSION: The results point out that the inversion or noninversion of tool
      effect movements plays an underlying role when handling a tool. APPLICATION:
      Potential applications of this research include the prediction and possibly
      manipulation of unwanted behavioral tendencies in laparoscopic surgery and other
      lever movements.

PMID- 21901937
TI  - Evaluation of eye metrics as a detector of fatigue.
AB  - OBJECTIVES: This study evaluated oculometrics as a detector of fatigue in Air
      Force-relevant tasks after sleep deprivation. Using the metrics of total eye
      closure duration (PERCLOS) and approximate entropy (ApEn), the relation between
      these eye metrics and fatigue-induced performance decrements was investigated.
      BACKGROUND: One damaging effect to the successful outcome of operational military
      missions is that attributed to sleep deprivation-induced fatigue. Consequently,
      there is interest in the development of reliable monitoring devices that can
      assess when an operator is overly fatigued. METHOD: Ten civilian participants
      volunteered to serve in this study. Each was trained on three performance tasks:
      target identification, unmanned aerial vehicle landing, and the psychomotor
      vigilance task (PVT). Experimental testing began after 14 hr awake and continued
      every 2 hr until 28 hr of sleep deprivation was reached. RESULTS: Performance on
      the PVT and target identification tasks declined significantly as the level of
      sleep deprivation increased.These performance declines were paralleled more
      closely by changes in the ApEn compared to the PERCLOS measure. CONCLUSION: The
      results provide evidence that the ApEn eye metric can be used to detect fatigue
      in relevant military aviation tasks. APPLICATION: Military and commercial
      operators could benefit from an alertness monitoring device.

PMID- 21901938
TI  - Validating an efficient method to quantify motion sickness.
AB  - OBJECTIVE: Motion sickness (MS) can be a debilitating side effect associated with
      motion in real or virtual environments. We analyzed the effect of expectancy on
      MS and propose and validate a fast and simple MS measure. BACKGROUND: Several
      questionnaires measure MS before or after stimulus presentation, but no
      satisfactory tool has been established to quickly capture MS data during
      exposure. To fill this gap, we introduce the Fast MS Scale (FMS), a verbal rating
      scale ranging from zero (no sickness at all) to 20 (frank sickness). Also, little
      is known about the role of expectancy effects in MS studies. We conducted an
      experiment that addressed this issue. METHOD: For this study, 126 volunteers
      participated in two experiments. During stimulus presentation, participants had
      to verbally rate the severity of MS every minute before filling in the Simulator
      Sickness Questionnaire (SSQ). To measure expectancy effects, participants were
      separated into three groups with either positive, negative, or neutral
      expectations. RESULTS: We compared the verbal ratings with the SSQ scores.
      Pearson correlations were high for both the SSQ total score (r = .785) and the
      nausea subscore (r = .828). No expectancy effects were found. CONCLUSION: The FMS
      is a fast and valid method to obtain MS data. It offers the possibility to record
      MS during stimulus presentation and to capture its time course. We found
      expectancy not to play a crucial role in MS. However, the FMS has some
      limitations. APPLICATION: The FMS offers improved MS measurement. It is fast and
      efficient and can be performed online in environments such as virtual reality.

PMID- 21901939
TI  - A respite from chikungunya for now.

PMID- 21901940
TI  - Genotype-phenotype diversity of beta-thalassemia in Malaysia: treatment options
      and emerging therapies.
AB  - The haemoglobinopathies and thalassemias represent the most common inherited
      monogenic disorders in the world. Beta-thalassaemia major is an ongoing public
      health problem in Malaysia. Prior to 2004, the country had no national policy for
      screening and registry for thalassemia. In the absence of a national audit, the
      true figure of the extent of thalassemia in the Malaysian population was largely
      presumptive from micro-mapping studies from various research workers in the
      country. The estimated carrier rate for beta-thalassemia in Malaysia is 3.5-4%.
      There were 4768 transfusion dependent thalassemia major patients as of May 2010
      (Data from National Thalassemia Registry).

PMID- 21901941
TI  - School scoliosis screening programme-a systematic review.
AB  - A systematic review on the effectiveness and cost-effectiveness of school
      scoliosis screening programme was carried out. A total of 248 relevant titles
      were identified, 117 abstracts were screened and 28 articles were included in the
      results. There was fair level of evidence to suggest that school scoliosis
      screening programme is safe, contributed to early detection and reduction of
      surgery. There was also evidence to suggest that school-based scoliosis screening
      programme is cost-effective. Based on the above review, screening for scoliosis
      among school children is recommended only for high risk group such as girls at
      twelve years of age.

PMID- 21901942
TI  - Current concepts in the management of carotid body tumours.
AB  - OBJECTIVE: To review the current management of carotid body tumours and examine
      our own experience at the Singapore General Hospital. STUDY DESIGN: Retrospective
      review. SUBJECTS AND METHODS: Case note review of patients treated by the
      Department of Otolaryngology Head and Neck Surgery, Singapore General Hospital
      over a period of nine years from January 1999 to December 2007. RESULTS: There
      were a total of ten patients. Eight patients underwent surgery with no mortality
      or major surgical morbidity. Mean follow-up was 3 years and 5 months with no
      evidence of recurrence. One patient had bilateral tumours and is under
      surveillance. The last patient had inoperable disease and received radiotherapy.
      CONCLUSION: Our series has shown that carotid body tumours can be safely removed
      surgically. If the internal carotid artery needs to be resected, we prefer the
      use of a Pruitt-Inahara shunt. Radiotherapy is reserved for large inoperable
      cases or patients not fit for surgery.

PMID- 21901943
TI  - Intravitreal injection of recombinant tissue plasminogen activator and pneumatic
      displacement of submacular haemorrhage.
AB  - We report a case of a patient with hypertension and ischaemic heart disease on
      anti-platelet treatment, who developed uniocular profound visual loss from a
      submacular haemorrhage secondary to valsalva retinopathy. He was treated with a
      combination of intravitreal recombinant tissue plasminogen activator (rtPA) and
      sulphur hexafluoride (SF6) gas followed by strict prone positioning. He
      demonstrated significant displacement of the haemorrhage and improvement of
      vision postoperatively.

PMID- 21901944
TI  - The development and validation of diabetes knowledge questionnaire for the
      Indigenous population in Malaysia.
AB  - The study's aim was to construct and validate a diabetes mellitus knowledge
      questionnaire in Bahasa Malaysia for Orang Asli (OA-DKQ). The questionnaire was
      administered to; case (Orang Asli) and control (administrative staff) groups at
      baseline and retested two weeks later. The Cronbach's Alpha was used to determine
      internal consistency and intraclass correlation coefficient (ICC) was used to
      determine test-retest reliability. The OA-DKQ has an internal consistency of
      0.806. These findings suggest the OA-DKQ is an acceptable instrument to assess
      knowledge and preventive behaviour in Orang Asli (86 words).

PMID- 21901945
TI  - Epidemiology of chikungunya in Malaysia: 2006-2009.
AB  - This is a retrospective cross-sectional study based on the database of clusters
      of patients with clinical diagnosis of chikungunya (CHIK) that were referred to
      the National Public Health Laboratory for diagnostic investigations from January
      2006 to December 2009. Of the 13,759 referred patients, a total of 6314 (45.9%)
      patients were laboratory confirmed to have CHIK and 7445 (54.1) patients were
      considered as clinical cases of CHIK by epidemiological link. Epidemic curves
      plotted using date of onset of illness for all referred clusters of cases showed
      that there were three unrelated outbreaks of CHIK in Malaysia from 2006 to 2009.
      There were two small outbreaks that occurred within the state of Perak in 2006.
      The cluster of cases in 2008 and 2009 were of related outbreak which started in
      Johor state and subsequently spread to various parts of Malaysia. The mean age of
      the patients was 37.0 years old and those patients in the laboratory confirmed
      group were significantly younger than those in the epidemiological linked group.
      The main presenting clinical features recorded in this study were fever,
      arthralgia, myalgia and rashes. Those patients in the laboratory confirmed group
      had a significant higher incidence of fever, arthralgia and rash than those in
      the epidemiological linked group.

PMID- 21901946
TI  - Spectrum of infections in splenectomised thalassaemia patients.
AB  - Splenectomised thalassaemia patients are at risk of developing sepsis. As the
      infection may be life-threatening, treatment should be sought and given promptly.
      A retrospective study was performed amongst our thalassaemia major patients who
      were splenectomised. The vaccination status of each patient and the types of
      infections seen were reviewed to obtain a local perspective. In our cohort of 49
      splenectomised patients, 25 patients required hospitalization for the treatment
      of infection. There were a total of 40 febrile episodes within this hospitalised
      group of which 27.5% were microbiologically documented infection with
      bacteraemia. The predominant causative organisms were gram negative rods and
      three patients succumbed to overwhelming septicaemic shock as a result of delayed
      presentation. Sixty percent of the febrile episodes were clinically documented
      infection and comprised mainly upper respiratory tract infections. Based on the
      spectrum of infections seen, there is a need to improve the patients' awareness
      level so that early treatment is sought. There is also a need to re-address the
      approach towards vaccination in this immunocompromised group of patients by
      administering a booster pneumococcal and influenza vaccination in an attempt to
      reduce morbidity.

PMID- 21901947
TI  - Risk-adjusted analysis of patients undergoing laparotomy using POSSUM and P
      POSSUM score in Queen Elizabeth Hospital, Sabah.
AB  - BACKGROUND: Scoring systems such as POSSUM and P-POSSUM have been developed to
      help predict mortality and morbidity in patients. The ratio of observed-to
      predicted (O/P ratio) mortality and morbidity has been used as a performance
      indicator to compare different procedures, clinicians or hospitals. The aim of
      this study was to assess the predictive value of POSSUM compared with P-POSSUM in
      patients undergoing laparotomy in Queen Elizabeth Hospital, Sabah. METHODS: 381
      patients over the age of 12 undergoing general surgical laparotomy between 1 May
      2006 and 30 April 2007 were prospectively enrolled. RESULTS: In general, POSSUM
      over-predicted mortality compared with P-POSSUM (O/P ratio: 0.366 versus 0.721).
      P-POSSUM was still poor at predicting mortality in the lowest and highest risk
      groups (O/P ratios: 0 and 0.438). Both systems over-predicted mortality in trauma
      (O/P ratios: POSSUM, 0.306; P-POSSUM, 0.459), younger patients (O/P ratios:
      POSSUM, 0.325; P-POSSUM, 0.622) and non-ICU patients (O/P ratios: POSSUM, 0.171;
      PPOSSUM, 0.421). P-POSSUM was significantly better than POSSUM in other age
      groups and ICU patients. In terms of morbidity, POSSUM was able to predict
      morbidity quite accurately with O/P ratio of 0.746 and performed equally well
      across the subgroup. POSSUM was poor in predicting morbidity in young patients
      (O/P ratio: 0.652) and non-ICU patients (O/P ratio: 0.543). CONCLUSION: P-POSSUM
      is a better overall predictor of mortality in patients undergoing laparotomy in
      this hospital compared to POSSUM. POSSUM is fairly accurate in predicting
      morbidity. However, further refinement is needed to improve its predictive value
      in specific areas, and so increase its utility in our local setting.

PMID- 21901949
TI  - A retrospective study of narrowband-UVB phototherapy for treatment of vitiligo in
      Malaysian patients.
AB  - Psoralen and ultraviolet light A (PUVA) was the mainstay of vitiligo treatment
      before the introduction of narrowband UVB(NB-UVB). Eighteen patients treated with
      NB-UVB in Hospital Kuala Lumpur were retrospectively analyzed. Eight patients had
      Fitzpatrick skin phototype III and 10 with phototype IV. The mean duration of
      disease was 7.3 +/- 5.4 years, and the mean body surface area affected was 19.3
      +/- 16.2%. Mean duration of treatment was 14.3 +/- 9.6 months, number of session
      113.5 +/- 88.6 times and cumulative dose 111.7 +/- 108.5 J/ cm2. Concomitant
      topical steroid was used in 88.9% patients. Repigmentation was moderate in 6
      (40%) patients, good in 3 (20%), while 3 (20%) achieved excellent results. One
      patient (6.6%) showed no response and 2 (13.3%) showed poor repigmentation. Three
      patients developed side effects. NB-UVB phototherapy results in satisfactory
      repigmentation in our vitiligo patients and should be offered as a treatment
      option.

PMID- 21901948
TI  - Epidemiological and clinical features of dengue versus other acute febrile
      illnesses amongst patients seen at government polyclinics.
AB  - Classical dengue fever is characterized by the clinical features of fever,
      headache, severe myalgia and occasionally rash, which can also be caused by a
      number of other viral and bacterial infections. Five hundred and fifty eight
      patients who fulfilled the criteria of clinical diagnosis of acute dengue from 4
      government outpatient polyclinics were recruited in this prospective field study.
      Of the 558 patients, 190 patients were categorized as acute dengue fever, 86 as
      recent dengue and 282 as non-dengue febrile illnesses based on the results of a
      number of laboratory tests. Epidemiological features of febrile patients showed
      that the mean age of patients in the dengue fever group was significantly younger
      in comparison with patients in the non-dengue group. There was no significant
      difference between the two groups with respect to gender but there was
      significant ethnic difference with foreign workers representing a higher
      proportion in the dengue fever group. Patients with acute dengue fever were more
      likely to have patient-reported rash and a history of dengue in family or
      neighbourhood but less likely to have respiratory symptoms, sore-throat and
      jaundice in comparison to patients with non-dengue febrile illnesses. As with
      patients with dengue fever, patients in the recent dengue group were more likely
      to have history of patient-reported rash and a history of dengue contact and less
      likely to have respiratory symptoms in comparison to patients with non-dengue
      febrile illnesses. In contrast to patients with dengue fever, patients in the
      recent dengue group were more likely to have abdominal pain and jaundice in
      comparison to non-dengue febrile patients. The finding strongly suggests that a
      proportion of patients in the recent dengue group may actually represent a subset
      of patients with acute dengue fever at the late stage of illness.

PMID- 21901950
TI  - Comparison of 0.5% ropivacaine and 0.5% levobupivacaine for infraclavicular
      brachial plexus block.
AB  - A prospective randomized double-blind study was conducted which involved, 60 ASA
      1-2, aged 18-65 years patients, who had elective or emergency orthopaedic
      surgeries of the upper limbs. They were randomly divided into two groups: Group I
      received 30 mls of 0.5% ropivacaine; and Group II received 0.5% levobupivacaine
      for infraclavicular brachial plexus block based on the coracoid approach. The
      onset time required for sensory block of all required dermatomes (C5-T1) and the
      onset time of motor block were documented. Based on the Visual Analogue Score,
      pain scores were recorded every 30 minutes during surgery and at the 6th hour.
      The mean onset time (SD) for sensory block with ropivacaine was 13.5 +/- 2.9
      minutes compared to levobupivacaine at 11.1 +/- 2.6 minutes (p = 0.003). The
      onset time for motor block was 19.0 +/- 2.7 minutes in Group I compared to 17.1
      +/- 2.6 minutes (p = 0.013) in Group II. Patients in both groups experienced both
      mild to moderate pain at the 6th hour. In conclusion, there were statistically
      significant differences in the onset-time for sensory and motor block. However,
      there was no statistically significant difference in terms of effectiveness of
      analgesia at the 6th hour. Although the clinical advantage of levobupivacine is
      not substantial, its safety profile becomes a major consideration in the choice
      of local anaesthetic for brachial plexus block where a large volume is required
      for an effective result.

PMID- 21901951
TI  - Management of isolated splenic injuries after blunt trauma: an institution's
      experience over 6 years.
AB  - Forty-two patients with traumatic blunt splenic injuries were admitted over a six
      year period. Vehicular-related collisions and fall from height accounted for the
      injuries in 38 (90.5%) of them. Eleven (26.2%) underwent immediate surgery (7
      splenectomy and 4 splenorrhaphy), while the remaining 31 patients were treated
      nonoperatively of which 3 underwent angio-embolisation. Twenty seven patients had
      either grade III or IV splenic injuries. Operative management was more likely in
      patients with lower haemoglobin or with more severe splenic injury. Nonoperative
      management can be adopted in patients with blunt isolated splenic injuries but
      operative management is still indispensable in certain instances.

PMID- 21901952
TI  - Dural tear post mastoidectomy repaired with Dura Gen.
AB  - Dural exposure may occur during the course of thinning the tegmen tympani and
      tegmen mastoideum in mastoid procedure. If large area of dura is exposed or
      lacerated, cerebrospinal fluid and brain herniation may enter the mastoid cavity.
      We report a case of a patient with injured dura mater and tegmen mastoideum
      during mastoidectomy for chronic suppurative otitis media with cholesteatoma
      managed by using DuraGen. The dura mater and tegmen defect healed totally showing
      the success of the procedure. A collagen matrix like DuraGen is an option for
      repairing dural tear in mastoid region.

PMID- 21901953
TI  - Bilateral pulmonary aspiration of teeth and the migration of a foreign body from
      one main bronchus to another.
AB  - INTRODUCTION: Foreign body aspiration in the adult airway is very rare. A
      neglected foreign body can occur when the patient is mentally challenged or is in
      an unconscious condition such as following trauma. The diagnosis can be delayed
      because there is no typical history of choking or breathing difficulty.
      OBJECTIVE: To report a case of bilateral pulmonary aspiration of avulsed teeth.
      One tooth migrated from the main bronchus on one side to the opposite side before
      removal. CASE SUMMARY: An unconscious, intubated elderly man was managed in ICU
      for one week before tracheostomy was performed. Bilateral pulmonary aspiration of
      teeth was diagnosed accidentally on routine chest radiographs two weeks later.
      Removal was done with rigid bronchoscopy. Extraction of the remaining loose teeth
      was performed. CONCLUSION: It is important to check for loose teeth in
      unconscious patients, especially those who warrant prolonged ventilation and oral
      toilet.

PMID- 21901954
TI  - Duodenal intussusception of Brunner's gland adenoma mimicking a pancreatic
      tumour.
AB  - Brunner's gland adenoma is a rare benign tumour of the duodenum. It is usually
      asymptomatic but may occasionally present with gastrointestinal haemorrhage and
      obstruction. We report a 40-year old lady, presenting with upper gastrointestinal
      bleeding and was found to have prolapsed and intussuscepted Brunner's gland
      adenoma of the duodenum, which mimicked the appearance of a tumour in the head of
      pancreas.

PMID- 21901955
TI  - Chronic rectal bleeding in Proteus syndrome.
AB  - Proteus Syndrome is a rare congenital hamartomatous disorder that typically
      manifests itself in overgrowth, vascular malformation and disregulation of fatty
      tissue. The tissues affected are commonly the limbs but can be of any tissue.
      Vascular anomalies are common and appear at random sites on the body. Diagnosis
      is often difficult leading to wrong treatment. We describe a case of a 17-year
      old girl with Proteus syndrome presented with symptomatic anaemia secondary to
      chronic rectal bleeding. Computed Tomography Angiogram of Abdomen and Pelvis
      confirmed the presence of rectal vascular malformations.

PMID- 21901956
TI  - Mistaken diagnosis of optic neuritis and the possible role of phosphodiasterase-5
      inhibitors (Sildenafil/Viagra).
AB  - The diagnosis of optic neuritis and particularly retrobulbar optic neuritis when
      atypical and not responsive to corticosteroid treatment may need to be revised.
      This is now especially so in male patients who should be questioned regarding
      their taking a phosphodiasterase-5 inhibitor in particular Viagra. The case
      history of such a patient is presented who sustained posterior ischaemic optic
      neuropathy mistaken for retrobulbar neuritis resulting in bilateral severe visual
      loss.

PMID- 21901957
TI  - Tracheal agenesis: a rare cause of unsuccessful tracheal intubation during
      resuscitation.
AB  - Tracheal agenesis is a rare congenital airway anomaly that usually results in a
      fatal outcome. The diagnosis is usually made through post-mortem examination. In
      the current literature, there has been no reported long-term survival although a
      few reports claimed prolongation of life of several hours to days. This condition
      is commonly associated with premature birth, polyhydramnios and a male
      predominance. In 90% of the cases, it is associated with multiple cardiovascular,
      gastrointestinal and genitourinary tract anomalies which are incompatible with
      life. We report a case of a premature newborn with severe respiratory distress,
      absent cry and cyanosis soon after birth. Attempts at endotracheal intubation
      failed as it was no possible to negotiate the tube beyond the vocal cords. Needle
      cricothyrotomy and attempted tracheostomy also failed to secure the airway. The
      diagnosis was confirmed at post-mortem examination.

PMID- 21901959
TI  - Care is priority, not costs.

PMID- 21901958
TI  - Computed tomography (CT) in blunt liver injury: a pictorial essay.
AB  - Computed tomography (CT) is widely used in assessing clinically stable patients
      with blunt abdominal trauma. In these patients, liver is one of the commonest
      organs being injured and CT can accurately identify and assess the extent of the
      injury. The CT features of blunt liver trauma include laceration, subcapsular or
      parenchymal haematomas, active haemorrhage and vascular injuries. Widespread use
      of CT has notably influenced the management of blunt liver injury from routine
      surgical to nonsurgical management. We present pictorial illustrations of various
      liver injuries depicted on CT in patients with blunt trauma.

PMID- 21901960
TI  - Staff to be asked if they would take industrial action on pensions.

PMID- 21901961
TI  - Troubled care home operator criticised for staff's long shifts.

PMID- 21901962
TI  - Lack of clinical teachers puts health visitors target in doubt.

PMID- 21901963
TI  - Supervisors could assess nurses as part of regulatory shake-up.

PMID- 21901964
TI  - If one hospital can give patients dignified care, all of them can.

PMID- 21901966
TI  - A spiritual workout.
AB  - Yoga is an ancient philosophy, bringing together the mind, body and spirit. Its
      health effects are described in the third article in our series on complementary
      and alternative medicine.

PMID- 21901965
TI  - One step at a time.
AB  - A cross-sector, nurse-led pilot project has reduced the number of falls in
      nursing homes. Now the work could be introduced elsewhere.

PMID- 21901967
TI  - Making contact.
AB  - Gay men can notify ex-partners of sexually transmitted infections through a
      messaging service being piloted at seven clinics.

PMID- 21901968
TI  - Intraosseous access and adults in the emergency department.
AB  - This article examines the use of the intraosseous route for obtaining vascular
      access in adults. It discusses indications for intraosseous access, the
      techniques and devices used, and contraindications.

PMID- 21901969
TI  - The role of diet in lowering blood pressure.
AB  - Alterations in diet are an important component of the lifestyle changes
      recommended to reduce blood pressure in patients with hypertension. This article
      provides an overview of healthy eating guidelines, reviews evidence for making
      specific types of dietary change with the aim of lowering blood pressure and
      outlines the nurse's role in supporting patients to make any changes.

PMID- 21901970
TI  - Promoting healthy eating and an active lifestyle in schoolchildren.
AB  - Nurses play an important role in promoting good health in patients. With the rise
      in childhood obesity, nutrition is of particular significance and community
      nurses should have an understanding of the nutritional needs of schoolchildren.
      This article outlines the association between diet and health and identifies
      strategies to promote healthy lifestyles in children.

PMID- 21901971
TI  - Faecal incontinence.

PMID- 21901972
TI  - Placement promotion.

PMID- 21901973
TI  - Accept only the best.

PMID- 21901974
TI  - Turn ideas into action.

PMID- 21901975
TI  - Simultaneous determination of ten ginsenosides in panacis quinquefolii radix by
      ultra performance liquid chromatography and quality evaluation based on
      chemometric methods.
AB  - A rapid, sensitive and reliable method based on ultra performance liquid
      chromatography coupled with a photodiode array detector (UPLC-PAD) was developed
      for both the quantitative analysis of ten bioactive ginsenosides and a chemical
      fingerprint analysis. The chromatography was performed on an ACQUITY UPLC BEH C18
      column using a gradient elution with acetonitrile/water as the mobile phase. To
      compare the UPLC fingerprints and to evaluate their quality, chemometric methods
      including similarity analysis (SA) and hierarchical-clustering analysis (HCA)
      were implemented when classifying the Panacis Quinquefolii Radix samples. The
      Panacis Quinquefolii Radix samples were successfully grouped in accordance with
      their geographic origins.

PMID- 21901976
TI  - Dissolution and spectrophotometric determination of astaxanthin in aqueous
      solutions.
AB  - The poor solubility of astaxanthin in water can cause problems during dissolution
      tests of dosage forms because they are usually performed in water-based media.
      The aim of this study was the development of a convenient dissolution medium and
      a method for a spectrophotometric determination of astaxanthin in an aqueous
      solution. Three surfactants in different concentrations were tested as solubility
      improving substances: sodium lauryl sulfate (SLS), polysorbate 80 (PS 80) and
      macrogolglycerol hydroxystearate (Cremophor RH 40, CR 40). Optimal conditions
      were determined. The dissolution of astaxanthin from solid dosage form is
      performed into 1000 g of a solution of sodium lauryl sulfate with the
      concentration 1.0% (w/w) at 37 degrees C by paddle method, 100 rotations per
      minute, dissolution time 30 minutes. The procedure is convenient for solid dosage
      forms with a content of 4 to 12 mg of astaxanthin. The spectrophotometric
      determination of astaxanthin in aqueous solution from the dissolution test is
      measured at 486 nm. The specific absorbance A(1%) 1cm for astaxanthin in water is
      2000, a sodium lauryl sulfate solution (1%) was used as a blank.

PMID- 21901977
TI  - Hollow fiber liquid-phase microextraction for the determination of nimesulide in
      human plasma and its application to a pharmacokinetic study.
AB  - A hollow fiber liquid-phase microextraction (HF-LPME) method in combination with
      HPLC-UV for the determination of nimesulide in human plasma was developed and
      validated. A small volume of dihexyl ether contained within a polypropylene
      hollow fiber was used for the extraction of nimesulide from acidified plasma
      solutions. Factors affecting the extraction efficiency were optimized and
      discussed. With HPLC-UV as the end analysis technique, the procedure was
      validated for nimesulide in the concentration range of 50-5000 ng/mL. The intra-
      and inter-assay precisions were less than 9.1%, and accuracy was within 3.2%. The
      lower limit of quantification (LLOQ) was 50 ng/mL. Enrichment factor from 144
      fold to 156-fold was achieved at three quality control (QC) concentrations. The
      mean extraction recovery was greater than 41.2%. This method was successfully
      applied for the evaluation of pharmacokinetics of nimesulide after single oral
      doses of 100 mg nimesulide to six healthy Chinese volunteers.

PMID- 21901978
TI  - Preparation of curcuminoid niosomes for enhancement of skin permeation.
AB  - Curcuminoids (curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin) are major
      bioactive substances found in turmeric (Curcuma longa L.) extracts and possess
      antioxidant, anti-inflammatory, antimicrobial and anticancer properties. In this
      study, curcuminoid niosomes prepared with a series of Span non-ionic surfactants
      were developed to enhance the skin permeation of curcuminoids. Formulations were
      evaluated based on aggregation of niosomes, curcuminoid loading, % entrapment
      efficiency and in vitro permeation of curcuminoids through shed snake skin.
      Optimal formulations of curcuminoid niosomes including sorbitan monooleate,
      cholesterol, and Solulan C-24 at a mole ratio of 47.5:47.5:5 were obtained. Up to
      11 micromoles of curcuminoids could be loaded in the niosome with a % entrapment
      efficiency of 83%. About 90% of the niosomes had a diameter of 12.25 +/- 5.00
      microm. The niosomes significantly enhanced permeation of curcuminoids compared
      with a methanolic solution of curcuminoids: 4% of entrapped curcuminoids
      traversed the shed snake skin, whereas permeation from the methanolic solution
      was undetectable. The fluxes of curcumin, desmethoxycurcumin, and
      bisdesmethoxycurcumin were 1.117, 0.263, and 0.057 microg/(cm2h), respectively,
      consistent with the relative hydrophobicity of curcumin > desmethoxycurcumin >
      bisdesmethoxycurcumin. In conclusion, our data show that curcuminoids can be
      successfully formulated as niosomes and that such formulations have improved
      properties for transdermal delivery.

PMID- 21901979
TI  - A burst drug release caused by imperfection of polymeric film-coated
      microparticles prepared by a fluidized bed coater.
AB  - The aim of this study was to investigate the drug release from microparticles
      coated with various polymeric films. Ibuprofen-loaded microparticles with
      diameter of 250 and 300 microm were prepared by a fluidized bed granulator. Five
      polymers were used as coating materials, i.e., ethylene vinyl acetate, ethyl
      cellulose, ethyl cellulose aqueous dispersion, polyethacrylate or Eudragit NE
      30D, and carnauba wax. The coating was performed with a fluidized bed coater.
      Afterwards the coated microparticles were characterized in terms of particle
      size, morphology, and drug content. The drug dissolution was also investigated in
      pH 7.4 phosphate buffer. In our attempts for production of extended release
      ibuprofen microparticles coated with polymeric films, it was shown that the
      coating process had a significant effect on drug release. The undesired burst
      release of ibuprofen was observed in all film-coated microparticulate
      formulations, resulting from the imperfection of coating films.

PMID- 21901980
TI  - Fosinopril-cyclodextrin inclusion complexes: phase solubility and physicochemical
      analysis.
AB  - Fosinopril is one of the most hydrophobic substances among the angiotensin
      converting enzyme inhibitors, exhibiting low water solubility and poor
      bioavailability following oral administration. Inclusion complexes between the
      drug substance and cyclodextrins (CDs) were obtained in order to improve its
      solubility. The purpose of this study was to investigate the guest-host
      interaction of fosinopril sodium (FOS) with beta-cyclodextrin (beta-CD) and its
      derivative, randomly methylated beta-cyclodextrin (RAMEB) in solution by phase
      solubility diagrams (PSD) and in solid state by using thermal analysis, powder X
      ray diffractometry (PXRD) and Fourier transform infrared spectroscopy (FTIR). The
      phase solubility analysis indicated that the solubility of FOS in simulated
      gastric fluid was increased in the presence of CDs and revealed for RAMEB an A(L)
      type diagram, suggesting the formation of a 1:1 inclusion complex, and for beta
      CD a B(s)-type phase diagram. The estimated apparent stability constant (K1:1),
      according to the Higuchi and Connors method, is 3209.99 M(-1) and 1770.34 M(-1)
      for RAMEB and beta-CD complexes respectively. The binary systems FOS/CDs were
      prepared using the kneading method in the molar ratio 1:1. The PXRD patterns and
      the thermograms indicated a drug amorphization process, higher for FOS/RAMEB
      binary system and the FTIR analysis suggested that the ester group of FOS is
      probably enclosed in the CD's cavity. The results of this study confirm the
      formation of inclusion complexes both in solution and in solid state and suggest
      that the complexes formation between FOS and CDs could improve the
      bioavailability of the drug due to the enhancing absorption expected from
      increased drug solubility.

PMID- 21901981
TI  - Bioequivalence evaluation of two brands of rivastigmine of different salt forms,
      an acetylcholinesterase inhibitor for the treatment of Alzheimer's disease, in
      healthy Beagle dogs.
AB  - The bioequivalence of two brands of rivastigmine capsules, of different salt
      forms, was demonstrated in six healthy beagle dogs after a single oral dose in a
      randomized cross-over study. Reference (Rivastigmine hydrochloride, Sunve, CN)
      and test (Rivastigmine tartrate, Novartis, CH) products were administered to
      fasting beagles on two treatment days separated by a two-day washout period;
      blood samples were collected at specified time intervals, and the plasma was
      separated and analyzed for rivastigmine using a validated GC-MS method. The
      pharmacokinetic parameters AUC(0-t), AUC(0-infinity), C(max), T(max) and t1/2
      were compared statistically to evaluate bioequivalence between the two brands,
      using the statistical modules recommended by the State Food and Drug
      Administration (SFDA) of China. The analysis of variance (ANOVA) did not show any
      significant difference between the two formulations and 90% confidence intervals
      fell within the acceptable ranges for bioequivalence. Based on these statistical
      inferences it was concluded that the two brands exhibited comparable
      pharmacokinetic profiles and that Sanwei's Rivastigmine hydrochloride was
      bioequivalent to Rivastigmine tartrate of Novartis, CH.

PMID- 21901982
TI  - Chitosan nanoparticles for controlled delivery of brimonidine tartrate to the
      ocular membrane.
AB  - Various efforts have been made to improve the bioavailability and to prolong the
      residence time of eye drops. Drug loaded polymeric nanoparticles offer several
      favorable biological properties. Thus, brimonidine tartrate (BT) loaded chitosan
      (CS) nanoparticles were prepared by inducing the ionic gelation upon addition of
      sodium tripolyphosphate (TPP). Nanoparticles were characterized by TEM, SEM,
      particle size, polydispersity index (PI), DSC, IR, entrapment efficiency which
      gave an insight of physicochemical interaction that influenced the CS
      nanoparticle formation and entrapment of BT. In vitro release of BT nanoparticle
      showed sustained release over the period of 4 h in saline phosphate buffer pH
      7.4. Both placebo and BT loaded nanoparticles had a mean particle size range of
      about 270-370 nm with PI less than 0.5. DSC studies demonstrated structural
      interactions between BT, TPP and CS matrix. Entrapment efficiency of the CS
      nanoparticles ranged from 36-49% depending on the CS:TPP weight ratio. In vivo
      studies confirmed a significant sustained effect of BT nanoparticles compared to
      conventional eye drops. These results suggest that BT loaded CS nanoparticles
      could help to reduce dosage frequency by sustained drug release in the treatment
      of glaucoma.

PMID- 21901983
TI  - Evaluation of hepatic clearance and drug-drug interactions of luteolin and
      apigenin by using primary cultured rat hepatocytes.
AB  - The hepatic clearance and drug-drug interactions of luteolin and apigenin were
      studied by using primary cultured rat hepatocytes. Luteolin and apigenin
      experienced extensive first-pass metabolism. The elimination percent of luteolin
      and apigenin was found to be 91.9% and 86.7% after 120 min of incubation. The
      predicted % liver blood flow was 82.3% and 85.4% for luteolin and apigenin,
      respectively. Total glucuronidated/sulfated conjugates of luteolin/apigenin were
      determined by an enzyme hydrolysis method. Compared with the elimination of pure
      luteolin and apigenin, the elimination of luteolin and apigenin was much lower in
      hydrolyzed Flos Chrysanthemi extract (FCE) containing comparable amounts of
      luteolin and apigenin. The effect of a series of flavonoids, including flavonols,
      flavones, isoflavone, flavanone, flavanonols and catechins, on the elimination of
      luteolin and apigenin was studied. At least four key determinants in the chemical
      structures of flavonoids are necessary for exerting the inhibitory effects on the
      conjugation: 1) catechol structure (3',4'-dihydroxylation) in the B-ring; 2) B
      ring is attached to the C-2 position on the C-ring; 3) the C2-3 double bond in
      conjunction with the C4 carbonyl group on the C-ring; 4) no glycoside present.
      Investigation of clearance and interaction among flavonoids could help us better
      understand their bioavailability and offer insight into the approaches to be
      taken to minimize competitive effects, and to design appropriate bioavailability
      studies in humans.

PMID- 21901984
TI  - The role of atorvastatin in bone metabolism in male albino Wistar rats.
AB  - OBJECTIVE: Statins have been widely used for the treatment of
      hypercholesterolemia, and recent studies have shown that these drugs also affect
      bone metabolism. The aim of this experiment was to follow the effect of
      atorvastatin on bone metabolism in male albino Wistar rats. METHODS: Our study
      was carried out on 16 rats (240 +/- 10g) which were randomly divided into 2
      groups of 8 animals. The control group (CO) was given aqua pro injectione (0.2
      mL/100 g BW; gavage) and the experimental group atorvastatin suspension (AT; 0.3
      mg in 0.2 mL aqua pro inj./100 g BW; gavage) daily for 8 weeks. We examined serum
      markers of bone turnover using ELISA - C-terminal crosslinking telopeptide of
      type I collagen (CTX-I), total osteocalcin (total OC), procollagen type I N
      propeptide (PINP) and bone alkaline phosphatase (bone ALP). We investigated bone
      morphogenetic protein-2 (BMP-2) in the proximal tibia using Western blot
      analysis. Additionally, we measured bone mineral density (BMD). The femurs were
      used for a three-point bending test and compression test of the femoral neck.
      RESULTS: After 8 weeks of atorvastatin administration, a significant decrease was
      found in serum level of bone ALP to 30% vs. CO (p = 0.005). PINP, CTX-I and OC
      did not change significantly. The expression of BMP-2 was increased. There were
      no significant differences in BMD measurements, three-point bending test or
      compression test of the femoral neck. CONCLUSIONS: Our results suggest that
      atorvastatin has a positive effect on bone metabolism in rats by maintenance of
      BMD and the biomechanical characteristics of bone. Atorvastatin influenced bone
      metabolism by decreasing bone ALP, and probably in consequence increasing
      expression of BMP-2 in rats.

PMID- 21901986
TI  - Valproic acid inhibits prostate cancer cell migration by up-regulating E-cadherin
      expression.
AB  - E-Cadherin plays important roles in cell-cell adhesion, epithelial-to-mesenchymal
      transition, cancer cell migration and invasion. Valproic acid (VPA), a well-known
      inhibitor of class I and class II histone deacetylases, has been considered a
      promising anticancer drug due to its capacity of inducing cancer cell
      proliferation arrest and death through different mechanisms. However, effects of
      VPA on E-cadherin mediated cell-cell adhesion and cancer cell migration remain
      unclear. In the present study, we found that VPA potently induced
      hyperacetylation of histone H3 and H4, increased the expression of E-cadherin and
      inhibited cell migration in prostate cancer cells. Furthermore, knock-down of E
      cadherin significantly restored the effects of VPA on cell migration, while over
      expression of E-cadherin in prostate cancer cells significantly inhibited cell
      migration to a similar level as VPA treatment. These results thus suggest that up
      regulation of E-cadherin and inhibition of cell migration may represent a new
      anticancer mechanism of VPA.

PMID- 21901985
TI  - Flouxetine treatment acts selectively increasing myocardial beta1-adrenoceptor
      mRNA expression in stress-induced depression.
AB  - Changes in gene expression of beta1- and beta2-adrenoceptors (beta1 - and beta2
      AR) in right and left atria and ventricles after fluoxetine treatment in stress
      induced depression of adult rat males were studied. Elevated beta1-AR mRNA levels
      in the left atria and significantly higher levels of beta2-AR mRNA in the left
      atria and ventricles were observed in stress-induced depression in comparison
      with those of unstressed controls. Fluoxetine treatment led to increasing
      expression of beta1-AR mRNA in the right atria and left ventricles, while the
      level of beta2-AR mRNA remained unchanged. These findings suggest that fluoxetine
      therapy plays an important role in cardiac beta-adrenergic subsensitivity and
      gene regulation of beta-AR in animals with heightened sympathetic nervous
      activity.

PMID- 21901987
TI  - Influence of antibiotic therapy on the level of selected angiogenic factors in
      patients with benign gynecologic tumors--preliminary report.
AB  - An increased fibrin level enhances the activity of proangiogenic factors and may
      contribute to tumor formation. Formation of new blood vessels during angiogenesis
      leads to neoplasm development through interaction with factors such as basic
      fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and
      interleukins. The aim of this study was to investigate the influence of
      perioperative antibiotic therapy in women with benign gynecological tumors with
      regard to basic fibroblast growth factor level, fibrinogen concentration and
      fibrin viscosity. The influence of clindamycin plus metronidazole therapy (group
      I) and cephazolin therapy (group II) on fibrinogen concentration, level of bFGF
      and fibrin viscosity was studied in women diagnosed with nonmalignant myomas and
      cysts. In patients with benign gynecologic tumors, higher bFGF levels (51.40 +/-
      13.72 pg/ml), fibrinogen concentration (348.26 +/- 164.74 mg/dl) and fibrin
      viscosity (2.63 +/- 0.36 mPa) were observed, as compared with healthy women.
      There were strong indications that antiangiogenic activity occurred with both
      clindamycin plus metronidazole and cephazolin, although the response to these
      particular antibiotic therapies was different. The use of various drug therapies
      in groups I and II resulted in faster and delayed antiangiogenic effects,
      respectively. Further research is essential to provide more detailed information
      about the mechanisms of the induction of antiangiogenic activity by perioperative
      adjuvant antibiotic treatment.

PMID- 21901988
TI  - Sedative, anxiolytic and antidepressant activities of Citrus limon (Burn)
      essential oil in mice.
AB  - We examined the sedative, anxiolytic and antidepressant effects of essential oil
      (EO) of leaves from Citrus limon, which has been used as one of the most popular
      compounds in Brazilian traditional herbal medicine. The effects of EO were
      demonstrated by open-field, elevated-plus-maze, rota rod, pentobarbital-induced
      sleeping time, and forced swimming tests in mice. In the open-field test, EO at
      the doses of 50, 100 and 150 mg/kg, after oral administration, significantly
      decreased the number of crossings, grooming, and rearing. In the elevated-plus
      maze (EPM) test, EO increased the time of permanence and the number of entrances
      in the open arms. On the contrary, the time of permanence and the number of
      entrances in the closed arms were decreased. In the rota rod test, EO did not
      alter motor coordination and, thus, was devoid of effects, as related to
      controls. In the pentobarbital-induced sleeping time test, EO at the same doses
      significantly increased the animals sleeping time duration. Since EO, at the
      doses of 50, 100 and 150 mg/kg, did not show a sedative effect in the open field
      test, these three doses were used in the forced swimming test, producing a
      decrease in the immobility time, similarly to that of imipramine (positive
      control). However, the antidepressant effects of EO were not altered by the
      previous administration of paroxetine. In addition, effects of EO in the forced
      swimming test were totally blocked by reserpine pretreatment. In conclusion, the
      present work evidenced sedative and anxiolytic effects of EO that might involve
      an action on benzodiazepine-type receptors, and also an antidepressant effect
      where noradrenergic and serotoninergic mechanisms will probably play a role.

PMID- 21901989
TI  - Growth inhibiting activity of lipophilic extracts from Dipsacus sylvestris Huds.
      roots against Borrelia burgdorferi s. s. in vitro.
AB  - Fresh first year roots from Dipsacus sylvestris HUDS. were extracted with 70%
      ethanol, ethyl acetate as well as dichloromethane. Extracts were solubilized in
      water (lipophilic extracts with addition of polysorbate 80) and tested for their
      activity against Borrelia burgdorferi sensu stricto in vitro during an eight-day
      period using amoxicillin as standard. The hydroethanolic extract showed no growth
      inhibition whereas significant growth inhibiting activity could be shown in the
      two less polar fractions for the first time. Strongest inhibition was found in
      the ethyl acetate extract. The effect of polysorbate 80 on bacterial growth was
      examined and found to be negligible. As the nature of bioactive constituents has
      not been clarified yet, a micellar electrokinetic capillary chromatography
      fingerprint analysis for a methanolic extract was applied including loganin,
      chlorogenic acid, cantleyoside and caffeic acid as marker substances.

PMID- 21901990
TI  - Stability of amoxicillin in portable pumps is drug concentration dependent.
AB  - Continuous amoxicillin infusion for deep infection's intravenous treatment is
      performed using elastomeric portable pumps carried under clothing and requires
      high doses of antibiotic. Therefore, we evaluated the stability of amoxicillin in
      those medical devices, with particular focus on both drug concentration and
      storage temperature. Stability of 20, 40, and 60g/L amoxicillin solutions in 300
      mL portable pumps stored at 20 or 35 degrees C was studied by visual examination
      and drug concentration measurements at T0; T0 + 12 h; T0 + 24 h and; T0 + 48 h.
      Twenty and 40 g/L amoxicillin solutions were stable over 48 h, with a degradation
      rate that never exceeded 12% at T0 + 24 h, and 18% at T 0 + 48 h. However, the 60
      g/L amoxicillin solution degradation rate was significant (p < 0.05, versus C1
      and C2) at T0 + 24 h: 24.5 and 26.9% at 20 and 35 degrees C, respectively. This
      degradation process was amplified at T0 + 48 h, with degradation rates of 37 and
      42% at 20 and 35 degrees C, respectively. Stability of amoxicillin in pump is
      guarantied over 48 h up to concentrations of 40 g/L. At 60 g/L major degradation
      of the antibiotic was observed.

PMID- 21901991
TI  - Lignans in Schisandra chinensis in vitro cultures.
AB  - Contents of schisandrol A and schisandrol B were determined in methanolic
      extracts of biomass from in vitro cultures of Schisandra chinensis (Turcz.)
      Baill. (Schisandraceae) using an HPLC method. The biomass was cultured on six
      variants of Murashige and Skoog (MS) medium containing different concentrations
      of growth regulators, cytokinin (BAP) and auxin (NAA). The contents of both
      lignans were different and dependent on the MS medium variant. The maximal
      contents of schisandrol A (70.54 mg/100 g d.w.) and schisandrol B (86.41 mg/100 g
      d.w.) were considerable in comparison with plant material: leaves (29.69 and
      34.50 mg/100 g d.w.) and fruits (132.39 and 109.40 mg/100 g d.w., respectively).
      This is the first report on the quantitative analysis of schisandrol A and
      schisandrol B in Schisandra chinensis in vitro cultures.

PMID- 21901992
TI  - Politicization: the power of influence.

PMID- 21901993
TI  - Parental depression, family functioning, and obesity among African American
      children.
AB  - Obesity has reached an epidemic level in America (National Center for Health
      Statistics [NCHS] 1999), and this epidemic is more acute for African Americans
      than for other groups ofAmericans. In this study, 44 parent-child dyads completed
      measurements of height, weight, depression, and body fat composition. In
      addition, parents completed a demographic questionnaire, and instruments, which
      measured family functioning, parental psychopathology, child behavior, and
      cardiovascular risks. Several models emerged for predicting childhood and
      parental body mass index, parental depression, and child behavioral problems.
      Findings indicated a role for parental depression in childhood obesity. These
      findings are discussed in light of Bandura 's Social Cognitive Theory, and the
      family's role in childhood obesity.

PMID- 21901994
TI  - Life stories of older adults with sickle cell disease.
AB  - Sickle cell disease (SCD) is a chronic disease with acute, painful exacerbations
      that often results in a shortened life expectancy. We explored the life stories
      of middle-age and older adults with SCD to ascertain how they explain their
      longevity and how they see the place of SCD in their lives. Data were gathered
      using semi-structured interviews with 12 individuals living with SCD--seven women
      and five men. Respondents offered four main reasons for their longevity: self
      care, supportive family/friends, a higher power, and medical care. Respondents
      reported life satisfactions of family, employment/education, and religious
      activities. The life stories reflect challenges of often living with a disease
      prior to diagnosis and without modern advances and the unpredictable nature of
      the disease. Their stories provide healthcare providers with insight into the
      supports SCD patients need to improve their health outcomes as they move through
      the life course.

PMID- 21901995
TI  - Evaluation of the Heart and Soul Physical Activity Program by African American
      women.
AB  - The purpose of this study was to determine the perceptions of African American
      (AA) women regarding an active lifestyle, and to evaluate the Heart and Soul
      Physical Activity Program (HSPAP) as a potential strategy to promote physical
      activity. The HSPAP is a church-based physical activity intervention
      conceptualized in appraisal, belonging, tangible and self-esteem domains of
      social support. Seven midlife, sedentary AA women from a Midwestern urban church
      participated in the group discussion after completing the HSPAP. Guiding
      questions were utilized to solicit their attitudes about physical activity and
      the HSPAP. The study participants believed that physical activity improves health
      and prevents chronic diseases however, their primary responsibility is to family
      and jobs, leaving little time or energy for their personal health needs. They
      further believed that physical activity would increase if recommended by health
      professionals and encouraged by family, friends, and church members; and, that
      spiritual messages and prayer would strengthen their commitment to attain an
      active lifestyle.

PMID- 21901996
TI  - Double-loop approach: recruitment and retention of minority nursing faculty.
AB  - A culturally diverse work force is vital to meeting the health care needs of an
      increasingly diverse population. The lack of minority faculty has been documented
      as a barrier to recruitment and retention of culturally diverse nursing students.
      Literature that addresses the nursing faculty shortage and the shortage of
      minority nurse educators is investigated. A double-loop approach to recruitment
      and retention of minority nursing faculty is proposed and includes the strategies
      of focused faculty searches, emphasizing internal resources of the academic
      institution, traditional and distance mentoring, nursing department initiatives,
      welcoming activities, and campus programs.

PMID- 21901997
TI  - Transforming the Medicaid transformation...or just new packaging?

PMID- 21901998
TI  - The prime directive: rational vs. rationing in healthcare.

PMID- 21901999
TI  - Hindsight's 20/20: lessons learned on the job.

PMID- 21902000
TI  - The Surgeon General's call to action to support breastfeeding: why all the fuss?

PMID- 21902001
TI  - Recognition, diagnosis and treatment of fetal alcohol syndrome.
AB  - Fetal Alcohol spectrum disorders are extremely common. The clinical impact and
      societal effects are tremendous. Prevention and treatment of these disorders
      begins with an accurate diagnosis. All health care providers who work with
      children (and adults) with special health care needs should be alert to these
      findings. The key to early diagnosis is to always keep the diagnostic possibility
      in the broad differential diagnoses of growth and developmental disorders. As
      with most conditions, early recognition and intervention is associated with
      better outcomes. Once an FASD is identified in a specific patient, prompt
      referrals and enrollment in indicated services are necessary to get the best
      outcomes. In this article we review the diagnostic criteria and clues to prompt
      early identification of FASDs. We also discuss the therapeutic options shown to
      be most effective for this group of individuals.

PMID- 21902002
TI  - Eating disorders in a rural state: two adolescent cases: a Hispanic male and a
      Korean female.
AB  - PURPOSE: The objective is to increase knowledge on eating disorder presentation
      and prevalence across age, gender and ethnicity. METHODS: Two adolescent ethnic
      minority cases diagnostically evaluated and treated at a multidisciplinary
      pediatric eating disorders specialty clinic in a rural state. RESULTS: A 14-year
      old Hispanic male presented with a history of a 22-pound weight loss over brief
      period, food restriction, over-exercising, excessive fears regarding weight. A 14
      year-old Korean female presented with a history of a 22-pound weight loss over
      brief period, severe food restriction, over-exercising, excessive fears regarding
      weight. CONCLUSIONS: It is important for professionals to increase their
      knowledge base and to become more comprehensively informed about eating disorders
      and to recognize that eating disorders are progressively becoming less
      discriminatory, impacting individuals across age, ethnicity, gender and
      socioeconomic status.

PMID- 21902004
TI  - Executive function in young children and chimpanzees (Pan troglodytes): evidence
      from a nonverbal dimensional change card sort task.
AB  - In this article the authors compared chimpanzees' executive function with that of
      children. They developed a nonverbal dimensional change card sorting task, which
      indexed the development of executive function. Three pairs of mother and
      offspring chimpanzees and 30 typically developed 5-year-old children were
      presented with 2 target stimuli and a test stimulus comprising 2 dimensions (size
      and shape) on a display; they were required to sort the test stimulus according
      to 1 dimension (e.g., shape). After 5 consecutive correct trials, the
      participants had to sort the test stimulus according to the other dimension
      (e.g., size). The results showed that the chimpanzees often failed to sort the
      test stimuli according to the first and reversed dimensions. On the other hand,
      the children were correctly able to use both dimensions. These results indicate
      that chimpanzees may have less developed executive skills than children.

PMID- 21902003
TI  - The development of prosocial behaviors in young children: a prospective
      population-based cohort study.
AB  - Researchers know relatively little about the normative development of children's
      behaviors aimed at alleviating distress or discomfort in others. In this article,
      the authors aim to describe the continuity and discontinuity in the degree to
      which young children in the general population are reported to exhibit specific
      prosocial behaviors. Data came from the Quebec Longitudinal Study of Child
      Development. Consistent with Hay's model of prosocial development, the results
      show that there were about as many children who stopped exhibiting prosocial
      behaviors between 29 and 41 months of age as there were children who started
      doing so during this period. Further, gender differences (girls > boys) in
      prosocial behaviors are either emerging or at least increasing in magnitude, with
      girls being more likely to start and boys being more likely to stop exhibiting
      these behaviors between 29 and 41 months of age. Consistent with the early-onset
      hypothesis, children who exhibit prosocial behaviors at 17 months of age are less
      likely to stop exhibiting the same behaviors between 29 and 41 months of age.
      Otherwise, if they did not exhibit prosocial behaviors at 29 months of age, they
      are also more likely to start doing so in the following year.

PMID- 21902005
TI  - Predictors of self-reported prospective and retrospective memory in a population
      based sample of older adults.
AB  - In this article, the authors examined predictors of self-reported everyday memory
      failures using the Prospective and Retrospective Questionnaire (PRMQ; Smith,
      Della Sala, Logie, & Maylor, 2000) in a population-based sample of older adults
      (age range = 60-90 years; N = 250). The results showed that a higher frequency of
      reported failures was associated with lower scores on the personality dimension
      of self-directedness as assessed by the Temperament and Character Inventory (TCI;
      Cloninger, Dragan, Svrakic, & Przybeck, 1993) and more depressive symptoms on the
      Center for Epidemiological Studies Depression Scale (CES-D; Radloff, 1977).
      However, PRMQ scores showed no relationships with objective memory ability, as
      reflected by a series of retrospective memory measures and a measure of
      prospective memory. Neither were the PRMQ scales associated with general
      cognitive functioning as assessed by the Mini-Mental State Examination (MMSE;
      Folstein, Folstein, & McHugh, 1977). Taken together, the results indicate that
      within the older population, self-reported memory as assessed by the PRMQ may
      reflect mood-state and personality factors rather than individual differences in
      memory and cognitive ability.

PMID- 21902006
TI  - Self-esteem accuracy and externalizing problems in preschool-aged boys.
AB  - Although the existing literature addressing the relation between self-esteem and
      externalizing problems is inconsistent, it appears that accuracy of self-esteem
      ratings may be an important factor to consider. However, no studies to date have
      explored this with preschool-aged children. In this study, the authors
      investigated differences in externalizing problems between underraters, realistic
      raters, and overraters of self-esteem of 5-year-old boys in three domains:
      cognitive competence, physical competence, and peer acceptance. Compared to
      teacher ratings of competence, boys who overrated their cognitive competence and
      peer acceptance were more likely to be rated by teachers as exhibiting more
      externalizing problems the following year. Findings suggest that overconfidence
      may have important implications for the development of externalizing problems in
      young children.

PMID- 21902007
TI  - Errors in identifying and expressing emotion in facial expressions, voices, and
      postures unique to social anxiety.
AB  - The purpose of the present study was to see if 7-10-year-old socially anxious
      children (n = 26) made systematic errors in identifying and sending emotions in
      facial expressions, paralanguage, and postures as compared with the more random
      errors of children who were inattentive-hyperactive (n = 21). It was found that
      socially anxious children made more errors in identifying anger and fear in
      children's facial expressions and anger in adults' postures and in expressing
      anger in their own facial expressions than did their inattentive-hyperactive
      peers. Results suggest that there may be systematic difficulties specifically in
      visual nonverbal emotion communication that contribute to the personal and social
      difficulties socially anxious children experience.

PMID- 21902008
TI  - Age and gender differences in morningness-eveningness during adolescence.
AB  - Morningness-eveningness was assessed in a large sample of adolescents and young
      adults. Morningness decreased from 12 to 15 years, and then remained on a stable
      level until about 20 years, when a turn back to morningness occurred. Boys and
      men were on average more evening-oriented than were girls and women. In detail,
      significant differences existed at the ages of 16, 18, and 19 years. A quadratic
      function explained more variance than a linear regression. Composite Scale of
      Morningness scores are related to puberty scores in boys and girls, and when
      combining data (i.e., higher pubertal development was related to eveningness).

PMID- 21902009
TI  - Formative versus reflective measurement: an illustration using work-family
      balance.
AB  - The aim of this article is to propose the formative measurement approach that can
      be used in various constructs of applied psychology. To illustrate this approach,
      the authors will (a) discuss the distinction between commonly used principal
      factor (reflective) measures in comparison to the composite (formative) latent
      variable model, which is often applied in other disciplines such as marketing or
      engineering, and (b) point out the advantages and limitations of formative
      specifications using the example of the work-family balance (WFB) construct. Data
      collected from 2 large cross-sectional field studies confirm the reliability and
      validity of formative WFB measures as well as its predictive value regarding
      criteria of WFB (i.e., job satisfaction, family satisfaction, and life
      satisfaction). Last, the specific informational value of each formative indicator
      will be demonstrated and discussed in terms of practical implications for the
      assessment in different psychological fields.

PMID- 21902010
TI  - Personality and American state differences in obesity prevalence.
AB  - The study was conducted to determine whether state obesity-prevalence rates can
      be predicted by state differences in residents' levels on the Big Five
      personality variables (O. P. John & S. Srivastava, 1999). State obesity
      prevalence was the mean percentage of the state population from 2000 to 2005 with
      a body mass index > or = 30.0 as assessed by the Behavioral Risk Factor
      Surveillance System (Centers for Disease Control and Prevention, 2010), which
      currently interviews more than 350,000 adults annually. State neuroticism,
      extraversion, agreeableness, conscientiousness, and openness z scores, based on
      the responses of 619,397 residents to an Internet survey from 1999 to 2005, were
      taken from P. J. Rentfrow, S. D. Gosling, and J. Potter (2008). Alaska, Hawaii,
      and North Dakota had scores outside -3 and +3 standard deviations on at least 1
      variable and were excluded as outliers. For the 47 remaining states, state
      obesity prevalence was significantly correlated with neuroticism (.35),
      agreeableness (.38), openness (-.44), socioeconomic status (-.74), white
      percentage (-.34), and urbanization (-.43). Multiple regression analysis showed
      that socioeconomic status could account for 54.0% of the criterion variance and
      that agreeableness, neuroticism, and openness together could account for another
      17.1%.

PMID- 21902011
TI  - Work-family and family-work conflict: does intrinsic-extrinsic satisfaction
      mediate the prediction of general job satisfaction?
AB  - The objective of this study is to analyze the mediating role of intrinsic and
      extrinsic job satisfaction in the relationship between the 2 dimensions of work
      family conflict-family interfering with work (FIW) and work interfering with
      family (WIF)-and general job satisfaction. Step-by-step hierarchical regression
      analyses were carried out on a sample of 151 men and women from a Spanish public
      organization. The results confirmed the mediating role of intrinsic job
      satisfaction in the case of FIW. This highlights the importance of taking into
      account the level of satisfaction with the intrinsic facets of one's job as a
      measure for understanding why FIW has a negative impact on general job
      satisfaction.

PMID- 21902012
TI  - The relationship of engagement and job satisfaction in working samples.
AB  - The present study explored the factor structure of engagement and its
      relationship with job satisfaction. The authors hypothesize that work engagement
      comprises 3 constructs: vigor, dedication, and absorption. Using structural
      equation modeling, the authors analyze data from 3 archival data sets to
      determine the factor structure of engagement. In addition, they examine the
      hypothesis that engagement and job satisfaction are separate but related
      constructs, using structural equation modeling and hierarchical regression. The
      authors test models in which engagement and job satisfaction items loaded onto a
      single latent variable and 1 in which they loaded onto 2 separate variables.
      Results from the confirmatory factor analysis indicate engagement has 3 factors.
      In addition, confirmatory factor analysis and hierarchical regressions indicate
      engagement and job satisfaction are separate constructs. Last, hierarchical
      regressions demonstrated the constructs have different relationships with the
      areas of work-life scale. Implications for theory and research are discussed.

PMID- 21902013
TI  - The antecedents and belief-polarized effects of thought confidence.
AB  - This article investigates 2 possible antecedents of thought confidence and
      explores the effects of confidence induced before or during ad exposure. The
      results of the experiments indicate that both consumers' dispositional optimism
      and spokesperson attractiveness have significant effects on consumers' confidence
      in thoughts that are generated after viewing the advertisement. Higher levels of
      thought confidence will influence the quality of the thoughts that people
      generate, lead to either positively or negatively polarized message processing,
      and therefore induce better or worse advertising effectiveness, depending on the
      valence of thoughts. The authors posit the belief-polarization hypothesis to
      explain these findings.

PMID- 21902015
TI  - Size fractionation characterisation of removed organics in reverse osmosis
      concentrates by ferric chloride.
AB  - Reverse osmosis membrane separation is the leading method for manufacturing
      potable purified water. It also produces a concentrate stream, namely reverse
      osmosis concentrates (ROC), with 10-20% of the water, and almost all other
      compounds. One method for further treating this stream is by coagulation with
      ferric chloride. This study evaluates removed organics in ROC treated with ferric
      chloride. Fractionation with ultrafiltration membranes allows separation of
      organics based on a nominal molecular weight. A stirred cell system was applied
      for serial fractionation to classify organic compounds into six groups of < 0.5
      kDa, 0.5-1 kDa, 1-3 kDa, 3-5 kDa, 5-10 kDa and > 10 kDa. The study found that raw
      ROC is rich in low molecular weight compounds (< 1 kDa) with almost 50% of the
      organics. These compounds include soluble microbial products (SMPs) and smaller
      humic and fulvic acids as indicated by fluorescence scanning. Conversely, colour
      was mostly contributed by medium to large molecules of humic and fulvic acids (>
      0.5 kDa). Organics and colour were reduced in all molecular groups at an optimum
      treatment dose 1.48 mM FeCl3 and a pH of 5. However, ferric seemed to effectively
      remove colour in all size ranges while residual nitrogen was found mostly in the
      < 1 kDa sizes. Further, the fluorescence indicated that larger humic and fulvic
      acids were removed with considerable SMPs remaining in the < 0.5 kDa.

PMID- 21902014
TI  - Gender-role conflict and gender-role orientation in a sample of gay men.
AB  - This exploratory study was designed to examine the relationship between gender
      role dimensions derived from the Bem Sex-Role Inventory (BSRI) and the 4
      dimensions of gender role conflict represented on the Gender Role Conflict Scale
      (GRCS) using a sample (N = 400) composed of exclusively gay men. Results from
      regression of 3 BSRI scores (femininity, social masculinity, personal
      masculinity) on the 4 subscale scores of the GRCS indicated that gender role
      conflict was most strongly and positively associated with the negative aspect of
      masculinity (social masculinity), accounting for about 11% of variability in
      social masculinity scores. In particular, the success-power-competition dimension
      of the GRCS was the major predictor of social masculinity in gay men. Gender role
      conflict was also strongly but negatively associated with femininity, accounting
      for approximately 10% of the variance in femininity scores among the men in the
      sample. Implications and recommendations for further studies are discussed.

PMID- 21902016
TI  - Mechanical resistance properties of gravel used in subsurface flow constructed
      wetlands: implications for clogging.
AB  - Gravel constitutes the filter medium in subsurface flow constructed wetlands (SSF
      CWs) and its porosity and hydraulic conductivity decrease over time (clogging),
      limiting the lifespan of the systems. Using gravel of poor quality accelerates
      clogging in wetlands. In this study, gravel samples from six different wetland
      systems were compared with regards to their mineral composition and mechanical
      resistance properties. Results showed that both mineralogy and texture are
      related to mechanical resistance. Accordingly, gravel with high content of quartz
      (> 80%) showed a lower percentage of broken particles (0.18-1.03%) than those
      with lower content of quartz (2.42-4.56% media broken). Although granite is
      formed by high durability minerals, its non-uniform texture results in a lower
      resistance to abrasion (ca. 10% less resistance than calcareous gravel).
      Therefore, it is recommended to use gravels composed mainly of quartz or, when it
      is not available, limestone gravels (rounded and uniform) are recommended
      instead. The resistance to abrasion (LAA test) seems to be a good indicator to
      determine the mechanical properties of gravels used in CWs. It is recommended to
      use gravels with LAA below 30% in order to avoid a rapid clogging due to gravel
      crumbling and subsequent mineral solids accumulation.

PMID- 21902017
TI  - Treatment of high loaded swine slurry in an aerobic granular reactor.
AB  - Aerobic granular sludge grown in a sequential batch reactor was proposed as an
      alternative to anaerobic processes for organic matter and nitrogen removal from
      swine slurry. Aerobic granulation was achieved with this wastewater after few
      days from start-up. On day 140 of operation, the granular properties were: 5 mm
      of average diameter, SVI of 32 mL (g VSS)(-1) and density around 55 g VSS
      (L(granule))(-1). Organic matter removal efficiencies up to 87% and nitrogen
      removal efficiencies up to 70% were achieved during the treatment of organic and
      nitrogen loading rates (OLR and NLR) of 4.4 kg COD m(-3) d(-1) and of 0.83 kg N
      m(-3) d(-1), respectively. However, nitrogen removal processes were negatively
      affected when applied OLR was 7.0 kg COD m(-3) d(-1) and NLR was 1.26 kg N m(-3)
      d(-1). The operational cycle of the reactor was modified by reducing the
      volumetric exchange ratio from 50 to 6% in order to be able to treat the raw
      slurry without dilution.

PMID- 21902018
TI  - Biofouling by bryozoans, Cordylophora and sponges in UK water treatment works.
AB  - In recent years biofouling from native (bryozoans, sponges) and non-native
      (Cordylophora) animals has increased in UK water treatment works (WTW). A survey
      of six UK water companies and eight WTWs revealed that these taxa were more
      widespread and abundant than previously recognised. Primary problems related to
      the occlusion of underfloor nozzles and tailpipes in rapid gravity filter beds
      (RGFs). These cost the UK water industry pound 1.49 m between 2005 and 2009.
      Additional impacts came from skin irritation to operatives from sponge spicules
      and the potential for elevated bacterial pathogen levels. Sponges penetrated the
      furthest through the water treatment process, reaching the point of final
      chlorination at one WTW. A monitoring plate study showed pronounced seasonality
      in fouling, with most taxa peaking in mid to late summer before a winter die-off.
      Control options, including the use of chlorine, and the importance of resistant
      stages for each taxon are discussed.

PMID- 21902019
TI  - Comparison of the role of attachment, aggregation and internalisation of
      microorganisms in UVC and UVA (solar) disinfection.
AB  - In this comparative study, the impact of two microbial protective mechanisms
      against simulated UVA disinfection was assessed by using protocols previously
      developed for UVC disinfection assays. (i) The impact of natural microorganism
      aggregation and attachment to particles was assessed by targeting total coliform
      bacteria in natural surface water samples. (ii) The impact of bacteria
      internalisation by zooplankton was assessed by using C. elegans nematodes as a
      model host and E. coli as a bacterial target for UVA inactivation. Dispersion of
      natural aggregates by blending prior to UVA exposure was shown to enhance the
      inactivation rate of total coliforms as compared to untreated raw water. Removal
      of particles by an 8-microm membrane filtration did not improve UVA disinfection
      efficiency. Twenty-four per cent of the highest applied UVA fluence was found to
      reach internalised E. coli in nematodes. Both aggregation and internalisation
      showed similar impact as protective mechanisms against UVA and UVC bacterial
      inactivation.

PMID- 21902020
TI  - Potential of organic filter materials for treating greywater to achieve
      irrigation quality: a review.
AB  - The objectives of this literature review were to: (i) evaluate the impact of
      greywater generated in rural communities, with the emphasis on Jordanian
      conditions, on soil, plant and public health and assess the need for treatment of
      this greywater before it is used for irrigation, and (ii) assess the potential of
      different types of organic by-products as carrier material in different filter
      units for removal of pollutants from greywater. Greywater with high BOD5, COD,
      high concentrations of SS, fat, oil and grease and high levels of surfactants is
      commonly found in rural areas in Jordan. Oxygen depletion, odour emission,
      hydrophobic soil phenomena, plant toxicity, blockage of piping systems and
      microbiological health risks are common problems associated with greywater
      without previous treatment. Organic by-products such as wood chips, bark, peat,
      wheat straw and corncob may be used as carrier material in so-called mulch
      filters for treating wastewater and greywater from different sources. A down-flow
      mode vertical filter is a common setup used in mulch filters. Wastewaters with a
      wide range of SS, cBOD5 and COD fed into different mulch filters have been
      studied. The different mulch materials achieved SS removal ranging between 51 and
      91%, a BOD5 reduction range of 55-99.9%, and COD removal of 51-98%. Most types of
      mulches achieved a higher organic matter removal than that achieved by an
      ordinary septic tank. Bark, peat and wood chips filters removed organic matter
      better than sand and trickling filters, under similar conditions. Release of
      filter material and increase in COD in the effluent was reported using some mulch
      materials. In conclusion, some mulch materials such as bark, peat and woodchips
      seem to have a great potential for treatment of greywater in robust, low-tech
      systems. They can be expected to be resilient in dealing with variable low and
      high organic loads and shock loads.

PMID- 21902021
TI  - Groundwater infiltration, surface water inflow and sewerage exfiltration
      considering hydrodynamic conditions in sewer systems.
AB  - Sewer systems are closely interlinked with groundwater and surface water. Due to
      leaks and regular openings in the sewer system (e.g. combined sewer overflow
      structures with sometimes reverse pressure conditions), groundwater infiltration
      and surface water inflow as well as exfiltration of sewage take place and cannot
      be avoided. In the paper a new hydrodynamic sewer network modelling approach will
      be presented, which includes--besides precipitation--hydrographs of groundwater
      and surface water as essential boundary conditions. The concept of the modelling
      approach and the models to describe the infiltration, inflow and exfiltration
      fluxes are described. The model application to the sewerage system of the City of
      Dresden during a flood event with complex conditions shows that the processes of
      infiltration, exfiltration and surface water inflows can be described with a
      higher reliability and accuracy, showing that surface water inflow causes a
      pronounced system reaction. Further, according to the simulation results, a high
      sensitivity of exfiltration rates on the in-sewer water levels and a relatively
      low influence of the dynamic conditions on the infiltration rates were found.

PMID- 21902022
TI  - Enhancement of anaerobic biohydrogen/methane production from cellulose using heat
      treated activated sludge.
AB  - Anaerobic digestion is an effective technology to convert cellulosic wastes to
      methane and hydrogen. Heat-treatment is a well known method to inhibit hydrogen
      consuming bacteria in using anaerobic mixed cultures for seeding. This study aims
      to investigate the effects of heat-treatment temperature and time on activated
      sludge for fermentative hydrogen production from alpha-cellulose by response
      surface methodology. Hydrogen and methane production was evaluated based on the
      production rate and yield (the ability of converting cellulose into hydrogen and
      methane) with heat-treated sludge as the seed at various temperatures (60-97
      degrees C) and times (20-60 min). Batch experiments were conducted at 55 degrees
      C and initial pH of 8.0. The results indicate that hydrogen and methane
      production yields peaked at 4.3 mmol H2/g cellulose and 11.6 mmol CH4/g cellulose
      using the seed activated sludge that was thermally treated at 60 degrees C for 40
      min. These parameter values are higher than those of no-treatment seed (HY 3.6
      mmol H2/g cellulose and MY 10.4 mmol CH4/g cellulose). The maximum hydrogen
      production rate of 26.0 mmol H2/L/d and methane production rate of 23.2 mmol
      CH4/L/d were obtained for the seed activated sludge that was thermally treated at
      70 degrees C for 50 min and 60 degrees C for 40 min, respectively.

PMID- 21902023
TI  - Low energy/cost desalination: low dose and low mean ion resident time in
      concentrate stream of electro-dialysis reversal.
AB  - Species, dose, and mean ion resident time (MIRT(c)) in the concentrate of electro
      dialysis reversal (EDR) desalination are analysed. In the classical EDR,
      dimensions, flow, and velocity of dilute and concentrate are equal; Langelier
      saturation index (LSI) and CaSO4 saturation are used to control the scaling and
      fouling processes in concentrate, as such LSI < + 2.16 for preventing CaCO3 from
      fouling and CaSO4 saturation level < 200 for averting CaSO4 from precipitation.
      If LSI is more than allowable limit, acid is added in concentrate to keep CaCO3
      continuously dissolving; if CaSO4 saturation level in concentrate is more than
      the allowable limit, sodium hexametaphosphate (SHMP) is added in concentrate to
      maintain CaSO4 dissolving. EDR, however, was successfully modernised to operate
      with the higher water recovery rate (R) without any anti-scalant and without
      acid; this new EDR operated with LSI at 2.29 and CaSO4 saturation level 358.9% at
      lower dose and lower MIRT(c). Dose and MIRT(c) are proposed to address the
      controlling process. Monographs for the acids and SHMP requirements, and for the
      desalting cost including desalting power, membrane surface area, and chemicals
      usage, are developed. By lowering R and polar reversal interval, EDR can be
      operated at MIRT(c) < 130 min; at MIRT(c0 < 130 min, desalting cost/ energy can
      be minimised by eliminating chemicals requirement.

PMID- 21902024
TI  - Modelling a turbidity current in Soyang reservoir (Korea) and its control using a
      selective withdrawal facility.
AB  - Persistent turbidity in reservoirs and their downstream after flood events is one
      of most important environmental issues in Korea. Recently, modification of
      withdrawal facility and installation of a new selective withdrawal structure
      (SWS) have been implemented for the mitigation of downstream impact and sediment
      loading into water treatment facilities. This study was to explore the
      characteristics of flood density flow induced into Soyang Reservoir and the
      transport processes of suspended sediments (SS) through application of coupled
      two-dimensional hydrodynamic and particle dynamic models (TM-1, TM-2 and TM-3).
      The TM-3 including a turbidity attenuation rate as a lumped parameter showed best
      performance in reproducing the magnitude and distribution of SS in the reservoir.
      The validated model was applied to evaluate the effectiveness of SWS, which was
      designed for the reservoir, with 6 different historical flood events. The
      magnitude of vertical mixing of the turbidity plume and its persistence within
      the reservoir were closely correlated to the ratio of the volume of turbidity
      flow to the total reservoir storage (the theta value). The operation of SWS
      showed a positive effect as long as theta is between 0.3 and 0.6 but negative
      when theta = 0.83 for the study reservoir, thus it should be optimized based on
      the theta value for a better management of the reservoir.

PMID- 21902025
TI  - Water balance modelling of alternate water sources at the household scale.
AB  - Alternate water sources are being implemented in urban areas to augment scheme
      water supplied by a water utility to homes. These sources include residential
      wells, rainwater tanks and greywater systems. Greater water efficiency can be
      achieved when these systems are designed to match a water source to a given
      demand based on both water quantity and quality parameters. In this way the use
      of an alternate water source can be maximised and the use of the high quality
      scheme water minimised. This paper examines the use of multiple alternate water
      sources sequentially to supply the same demand point potentially optimising the
      use of all available water sources. It also allows correct sizing of such water
      systems and their components to reduce scheme water demand. A decision support
      tool based on water balance modelling was developed that considers such water
      options at the household scale. Application of this tool to eight scenarios for
      both large and small house lots shows that using alternate water sources
      individually can result in significant scheme water savings. However by
      integrating these sources additional scheme water saving can be made.

PMID- 21902026
TI  - Application of biofilm reactors to improve ammonia oxidation in low nitrogen
      loaded wastewater.
AB  - An airlift reactor using zeolite particles as carrier material was used for the
      nitrification of effluents from the aquaculture industry. During the start-up the
      nitrogen concentration was kept around 100 mg NH4(+)-N/L to develop the
      nitrifying population. Later it was decreased down to around 3 mg NH4(+)-N/L and
      the dilution rate was increased up to 4.8 d(-1) in order to simulate the
      conditions in a an aquaculture waster treatment system. A nitrogen loading rate
      (NLR) of 535 mg NH(+)-N/m2 d was fully oxidized to nitrate. Higher values of NLRs
      caused nitrite accumulation. A second biofilm reactor was fed with a synthetic
      medium containing 50 mg NH4(+)-N/L which simulated the effluents from anaerobic
      units treating domestic wastewater. A nitrogen loading rate of 400 mg NH4(+)-N/L
      d was oxidized into nitrate with an efficiency of 60% at a dilution rate of 8 d(
      1). Both biofilm systems allowed the development of a nitrifying population to
      treat the studied types of wastewaters.

PMID- 21902027
TI  - A combined UASB-MBR with shortcut nitrification-denitrification for energy
      reduction in wastewater reclamation.
AB  - Shortcut nitrification has been successfully applied in a laboratory scale
      nitrification-denitrification process consisting of an up-flow anaerobic sludge
      blanket (UASB) and an aerobic membrane bioreactor (MBR) in treating synthetic and
      municipal wastewater to simultaneously remove organic carbon and nitrogen. For
      the treatment of synthetic wastewater, the combined system exhibited a high TOC
      removal of 98% with a steady ammonia removal efficiency of about 98% in the MBR
      and a total nitrogen (TN) removal efficiency of 90%. In treating municipal
      wastewater, due to its low COD concentration, removal efficiencies of TOC,
      ammonia and TN were 70%, 98% and 60%, respectively. The biogas production was
      around 76.4 L/m3 wastewater when treating synthetic wastewater. However, little
      biogas was produced when treating municipal wastewater which was the result of
      low organic carbon loading to the UASB. Energy analysis has demonstrated that
      this novel shortcut nitrification process could consume less energy than a
      conventional process and have the potential of bio-energy generation via biogas
      production thus helping to achieve a more favorable energy balance.

PMID- 21902028
TI  - Decolorization and mineralization of Oolong tea polyphenols in colored soft drink
      wastewater by photo Fenton reaction.
AB  - The decolorization and the mineralization of the colored soft drink wastewater
      including Oolong tea polyphenols by the photo Fenton reaction have been
      investigated. The decolorization of the colored soft drink wastewater including
      Oolong tea polyphenols by the photo Fenton reaction could be divided into 3
      phases. Just after H2O2 was added to the solution, the color of the solution
      immediately increased from absorbance of 0.247 to 0.711 at the wavelength of 400
      nm, which was defined as the 1st phase. Subsequently the significant
      decolorization by the photo Fenton reaction occurred at the 2nd phase. Finally,
      complete decolorization (the color attributed to the color of Fe3+) could be
      achieved in 180 min at the 3rd phase. The instantaneous and considerable color
      increase at the 1st phase could be attributed to the formation of intermediate
      colored compounds like quinones and soluble iron complexes produced by the Fenton
      reaction. About 95% mineralization of model colored soft drink wastewater with
      229 mg L(-1) initial TOC concentration was achieved after 165 min.

PMID- 21902029
TI  - Poyang Lake basin: a successful, large-scale integrated basin management model
      for developing countries.
AB  - Protection of water environment while developing socio-economy is a challenging
      task for lake regions of many developing countries. Poyang Lake is the largest
      fresh water lake in China, with its total drainage area of 160,000 km2. In spite
      of rapid development of socio-economy in Poyang Lake region in the past several
      decades, water in Poyang Lake is of good quality and is known as the "last pot of
      clear water" of the Yangtze River Basin in China. In this paper, the reasons of
      "last pot of clear water" of Poyang Lake were analysed to demonstrate how
      economic development and environmental protection can be coordinated. There are
      three main reasons for contributing to this coordinated development: 1) the
      unique geomorphologic features of Poyang Lake and the short water residence time;
      2) the matching of the basin physical boundary with the administrative boundary;
      and 3) the implementation of "Mountain-River-Lake Program" (MRL), with the
      ecosystem concept of "mountain as source, river as connection flow, and lake as
      storage". In addition, a series of actions have been taken to coordinate
      development, utilisation, management and protection in the Poyang Lake basin. Our
      key experiences are: considering all basin components when focusing on lake
      environment protection is a guiding principle; raising the living standard of
      people through implementation of various eco-economic projects or models in the
      basin is the most important strategy; preventing soil and water erosion is
      critical for protecting water sources; and establishing an effective governance
      mechanism for basin management is essential. This successful, large-scale basin
      management model can be extended to any basin or lake regions of developing
      countries where both environmental protection and economic development are needed
      and coordinated.

PMID- 21902030
TI  - Investigation of long-term operation and biomass activity in a membrane
      bioreactor system.
AB  - The aim of this work was to evaluate the long-term performance of a Membrane
      Bioreactor (MBR) that operated continuously for 2.5 years and to assess membrane
      fouling and biomass activity under various operating conditions. Furthermore, a
      method for the characterisation of influent wastewater was developed based on its
      separation into various fractions. The MBR system operated at the solids
      retention times (SRT) of 10, 15, 20 and 33 days. The increase of SRT resulted in
      a decrease of the fouling rate associated with the reduction of extracellular
      polymeric substances. Moreover, the SRT increase resulted in a significant
      reduction of the Oxygen Uptake Rate (OUR) due to the lower availability of
      substrate and in a notable decrease of the maximum OUR since high SRT allowed the
      development of slower growing microorganisms. Biomass consisted of small flocs
      due to extensive deflocculation caused by intense aeration. Finally, the method
      developed for wastewater characterisation is straightforward and less time
      consuming than the usual method that is employed.

PMID- 21902031
TI  - Assessment of data and parameter uncertainties in integrated water-quality model.
AB  - In integrated urban drainage water quality models, due to the fact that
      integrated approaches are basically a cascade of sub-models (simulating sewer
      system, wastewater treatment plant and receiving water body), uncertainty
      produced in one sub-model propagates to the following ones depending on the model
      structure, the estimation of parameters and the availability and uncertainty of
      measurements in the different parts of the system. Uncertainty basically
      propagates throughout a chain of models in which simulation output from upstream
      models is transferred to the downstream ones as input. The overall uncertainty
      can differ from the simple sum of uncertainties generated in each sub-model,
      depending on well-known uncertainty accumulation problems. The present paper aims
      to study the uncertainty propagation throughout an integrated urban water-quality
      model. At this scope, a parsimonious bespoke integrated model has been used
      allowing analysis of the combinative effect between different sub-models.
      Particularly, the data and parameter uncertainty have been assessed and compared
      by means of the variance decomposition concept. The integrated model and the
      methodology for the uncertainty decomposition have been applied to a complex
      integrated catchment: the Nocella basin (Italy). The results show that
      uncertainty contribution due to the model structure is higher with respect to the
      other sources of uncertainty.

PMID- 21902032
TI  - Effects of aquifer thermal energy storage on groundwater quality and the
      consequences for drinking water production: a case study from The Netherlands.
AB  - We used data from an aquifer thermal energy storage (ATES) system located 570 m
      from a public water supply well field in the south of The Netherlands to
      investigate the relation between production of renewable energy with an ATES
      system and the production of drinking water. The data show that the groundwater
      circulation by the ATES system can impact chemical groundwater quality by
      introducing shallow groundwater with a different chemical composition at greater
      depth. However, the observed concentration changes are sufficiently small to keep
      groundwater suitable for drinking water production. Microbiological results
      showed that the ATES system introduced faecal bacteria in the groundwater and
      stimulated the growth of heterotrophic micro-organisms. At the studied site this
      forms no hygienic risk because of the long distance between the ATES wells and
      the public supply well field A further degradation of either chemical or
      microbiological groundwater quality however may necessitate additional water
      treatment which raises the energy requirements. The additional energy
      requirements for drinking water treatment may be up the same order of magnitude
      as the harvested energy by the ATES system.

PMID- 21902033
TI  - Applicability of MIKE 21 to assess temporal and spatial variation in water
      quality of an estuary under the impact of effluent from an industrial estate.
AB  - This study aims at analysing the impact of wastewater load of industrial units in
      Haldia on the water quality of the Hoogly estuary using numerical modelling
      techniques. Modelling was never attempted in this region because it was generally
      felt that simulating such a complex system would not be easy with limited data
      availability but MIKE 21, a hydrodynamic and water quality model, was used to
      simulate BOD and DO profiles in the study area and simulation provided reasonably
      good predictions. A scenario assessment was also carried by increasing the flows
      from various sources to understand the site-specific relationships between
      pollution sources and water quality conditions and also to calculate the
      assimilative capacity of Hoogly with respect to waste discharged from the
      industrial units at Haldia. The results suggested that water quality of the canal
      towards closed Oil Jetty was highly deteriorated due to stagnant pond condition
      and discharges from a refinery. But large part of the canal was found to be well
      drained under tidal influence as a consequence of which both DO and BOD conform
      to the prescribed water quality standards most of the times. The impact of
      industrial waste load on the Hoogly was found to be negligible and the radius of
      influence was limited to about 200-300 m across the estuary and about 1.6 km
      along the shore during ebb conditions. Assimilative capacity of the region was
      estimated to be 837 kg/d as against the present load of 121 kg/d. The study
      suggested that the estuary had good dilution capacity and intense tidal mixing
      helped in rapidly diluting the pollutants.

PMID- 21902034
TI  - The effectiveness of humic acids coagulation with the use of cationic
      polyacrylamides.
AB  - The chemical coagulation process is a popular method for eliminating the
      precursors of disinfection by-products. This study presents the results of a
      laboratory experiment which investigates the use of cationic polyacrylamide
      copolymers (CPAMs) as primary coagulants in the purification of solutions
      containing humic acids (HA). A number of polymers with various molecular weight
      and charge density were tested. The optimal doses were determined by colloidal
      titration. The effectiveness of coagulation-flocculation was determined by jar
      test method. The post-coagulation suspension was separated by filtration through
      cellulose filter paper. The experiment showed that charge neutralization
      destabilizes organic colloidal particles. An inversely proportional relationship
      was observed between the optimal dose and polymer charge density. The
      effectiveness of UV254 reduction (52-81%) and colour removal (51-88%) was
      determined by the effectiveness of filtration in removing post-coagulation
      turbidity, as well as by the type of applied polymer. The results of the study
      suggest that the use of CPAMs with high charge density and low molecular weight
      enables effective removal of humic acids from water in the coagulation and
      filtration process.

PMID- 21902035
TI  - Determination of reaction rate constants for phenol oxidation using SnO2/Ti
      anodes coupled with activated carbon adsorption in the presence of TiO2 as
      catalyst.
AB  - Series of experiments for phenol degradation with assistance of TiO2 catalyst at
      pH of 6.5 and temperature of 25 degrees C were conducted using a lab-scale
      electrochemical reactor constructed in our laboratory. According to the results,
      at the presence of the TiO2 catalyst the removal of phenol was increased and
      first-order kinetics could describe the evolution of phenol concentration. For
      inspecting the relationship between rate constants and dosage of TiO2, two
      possible kinetics were proposed in this study. Contrasted to the abundant
      experimental data, a reasonable kinetics was obtained for the estimation of
      phenol concentration effluent during continuous flow of raw wastewater,
      especially when the TiO2 dosage was less than 0.5g L(-1). The model obtained from
      these experiments could employed for the calculation of rate constants at
      different TiO2 dosage and the necessary dosage of catalyst when a discharge
      standard was designed.

PMID- 21902036
TI  - Impact of copper and cadmium on aerobic and anaerobic digestibility of sonicated
      sludge.
AB  - The effects of the introduction of a sludge reduction process such as ultrasound
      on batch aerobic and anaerobic biodegradability after exposition to two metals
      (copper and cadmium) were investigated. The specific energy of ultrasonic
      treatment applied to the sludge was 200,000 kJ kg TS(-1). Ultrasonic treatment
      led to floc size reduction and to organic matter solubilization. Low copper (< 5
      mg L(-1)) and cadmium (< 1 mg L(-1)) concentration improved aerobic
      biodegradability. For high metal concentration the maximal instantaneous biogas
      production rate q(max) inhibition by copper and cadmium was modeled by a
      saturation-type relationship under aerobic and anaerobic conditions. Under
      aerobic conditions, respiration inhibition was not affected by sonication.
      Cadmium inhibition (74%) was more than copper (58%). The positive effect of
      sonication on CO2 production was maintained after metal introduction. Under
      anaerobic conditions, metal introduction cancelled out the positive effect of the
      treatment. The sonicated sludge was 16% less sensitive to copper inhibition but
      10% more sensitive to cadmium inhibition compared to non sonicated sludge.

PMID- 21902037
TI  - Influent concentrations and removal performances of metals through municipal
      wastewater treatment processes.
AB  - This extensive study aimed at quantifying the concentrations and removal
      efficiency of 23 metals and metalloids in domestic wastewater passing through
      full-scale plants. Nine facilities were equipped with secondary biological
      treatment and three facilities were equipped with a tertiary treatment stage. The
      metals investigated were Li, B, Al, Ti, V, Cr, Fe, Ni, Co, Cu, Zn, As, Se, Rb,
      Mo, Ag, Cd, Sn, Sb, Ba, TI, Pb and U. Particulate and dissolved metals were
      measured using 24 h composite samples at each treatment stage. In influents,
      total concentrations of Cd, Sb, Co, Se, U, Ag, V were below a few microg/L,
      whereas at the other extremity Zn, B, Fe, Ti, Al were in the range of 0.1 to > 1
      mg/L. It was demonstrated that secondary treatment stage (activated sludge,
      biodisc and membrane bioreactor) were efficient to remove most metals (removal
      rate > 70%), with the exception of B, Li, Rb, Mo, Co, As, Sb and V due to their
      low adsorption capacities. With the tested tertiary stages (polishing pond, rapid
      chemical settler, ozonation), a removal efficiency was obtained for Ti, Cr, Cd,
      Cu, Zn, Sn, Pb, Fe, Ag and Al, whereas a little removal (< 30%) was obtained for
      other metals.

PMID- 21902038
TI  - Leaching of additives from construction materials to urban storm water runoff.
AB  - Urban water management requires further clarification about pollutants in storm
      water. Little is known about the release of organic additives used in
      construction materials and the impact of these compounds to storm water runoff.
      We investigated sources and pathways of additives used in construction materials,
      i.e., biocides in facades' render as well as root protection products in bitumen
      membranes for rooftops. Under wet-weather conditions, the concentrations of
      diuron, terbutryn, carbendazim, irgarol 1051 (all from facades) and mecoprop in
      storm water and receiving water exceeded the predicted no-effect concentrations
      values and the Swiss water quality standard of 0.1 microg/L. Under laboratory
      conditions maximum concentrations of additives were in the range of a few
      milligrams and a few hundred micrograms per litre in runoff of facades and
      bitumen membranes. Runoff from aged materials shows approximately one to two
      orders of magnitude lower concentrations. Concentrations decreased also during
      individual runoff events. In storm water and receiving water the occurrence of
      additives did not follow the typical first flush model. This can be explained by
      the release lasting over the time of rainfall and the complexity of the drainage
      network. Beside the amounts used, the impact of construction materials containing
      hazardous additives on water quality is related clearly to the age of the
      buildings and the separated sewer network. The development of improved products
      regarding release of hazardous additives is the most efficient way of reducing
      the pollutant load from construction materials in storm water runoff.

PMID- 21902039
TI  - The connection between water and energy in cities: a review.
AB  - We have only rudimentary understanding of the complex and pervasive connections
      between water and energy in cities. As water security now threatens energy and
      economic security, this is a major omission. Understanding the water-energy nexus
      is necessary if we want to contribute to solving water and energy issues
      simultaneously; if we want to stop moving problems from one resource dimension to
      another. This is particularly relevant in the Australian context where energy use
      for water supplies is forecast to rapidly escalate, growing around 300% from 2007
      levels, by 2030. This paper presents a literature review with an aim of
      characterising the research to date with a particular focus on cities, the major
      centres of consumption and growth. It systematically analyses a wide range of
      papers and summarises the diverse objectives, dimensions, and scale of the
      research to-date together with knowledge gaps. There are many major gaps. These
      include energy use associated with water in industrial and commercial operations
      as well as socio-political perspectives. A major gap is the lack of a unifying
      theoretical framework and consistent methodology for analysis. This is considered
      a prerequisite for quantitative trans-city comparisons.

PMID- 21902040
TI  - Nitrogen removal from digested manure in a simple one-stage process.
AB  - A process based on partial nitrification and recirculation into the anaerobic
      digester was studied to remove nitrogen from digested manure and thus reduce
      enhanced gaseous ammonia emissions due to on-farm biogas production. An anaerobic
      reactor representing an anaerobic manure digester was fed with a nitrite solution
      and digested manure liquor. Nitrite was efficiently removed from the influent and
      ammonium formation was observed first. Ammonium was subsequently eliminated up to
      a maximum of 90% of the influent concentration, indicating anaerobic ammonium
      oxidation activity. This activity, however, decreased again and was lost at the
      end of the 4-month operation period. In a 1.5 L aerobic CSTR that was fed with
      digested manure liquor, ammonium was efficiently removed from the influent.
      Nitrite and nitrate formation was observed but mass balances indicated
      significant N-removal. Accumulation of suspended solids was observed at the end
      of the experiment suggesting presence of oxygen-free environments. In a second
      test in a 15 L CSTR where suspended solids sedimentation could be avoided, low N
      removal rates were observed in the absence of biofilm carrier elements whereas
      high N-removal rates were achieved in their presence. A simple one-stage process
      based on immobilized biomass could therefore be installed downstream of
      agricultural anaerobic digesters in order to mitigate undesirable gaseous ammonia
      emissions.

PMID- 21902041
TI  - An antimicrobial polycationic sand filter for water disinfection.
AB  - A new sand filtration water disinfection technology is developed which relies on
      the antimicrobial properties of hydrophobic polycations (N-hexylated
      polyethylenimine) covalently attached to the sand's surface. The efficacy of the
      filter disinfection process was evaluated both with water spiked with E. coli and
      with real aqueous effluent from a wastewater treatment plant. For the former,
      over 7-log reduction in bacterial count was achieved. With real environmental
      wastewater secondary effluent samples, the E. coli concentration reduction
      declined to under 2 logs. This reduced inactivation efficiency compared to the
      model aqueous sample is likely due to the particulate or colloidal matter present
      that diminishes the contact between the immobilized polycation and the suspended
      bacteria. Preliminary sand washing methods were tested to assess potential
      'regeneration' approaches. Potential advantages of the proposed approach over
      conventional disinfection in terms of eliminating harmful by-products and
      reducing energy consumption are discussed.

PMID- 21902042
TI  - Wastewater as a resource: a unique approach to achieving energy sustainability.
AB  - A wastewater-treatment flowsheet was developed to integrate uniquely designed
      biological processes with physical-chemical unit processes, allowing conversion
      of the organic carbon in the wastewater to methane, the removal and recovery of
      phosphorus and nitrogen from the wastewater, and the production of water suitable
      for reuse. In the flowsheet, energy is derived from the wastewater by first
      shunting a large fraction of the organic carbon in the wastewater to a solids
      slurry which is treated via anaerobic digestion. The anaerobic digestion system
      consists of focused pulsed (FP) pretreatment coupled to anaerobic membrane
      bioreactors (MBRs). Computer modelling and simulation results are used to
      optimize design of the system. Energy generation from the system is maximized and
      costs are reduced by using modest levels of recycle flow from the anaerobic MBRS
      to the FP pretreatment step.

PMID- 21902043
TI  - Inactivation of Pseudomonas aeruginosa in electrochemical advanced oxidation
      process with diamond electrodes.
AB  - The electrochemical advanced oxidation process (EAOP) with diamond electrodes may
      serve as an additional technology to the currently approved methods for water
      disinfection. Only few data exist on the microbicidal effect of the EAOP. The aim
      of our study was to investigate the microbicidal effect of a flow-through
      oxidation cell with diamond electrodes, using Pseudomonas aeruginosa as the test
      organism. Without electrical current the EAOP had no measurable effect on
      investigated microbiological and chemical parameters. For direct electrical
      current a stronger impact was observed at low flow rate than at higher flow rate.
      Depending on the contact time of the oxidants and the type of quenching reagent
      added, inactivation of P. aeruginosa was in the range log 1.6-3.6 at the higher
      flow rate and log 2.4-4.4 at the lower rate. Direct electrical current showed a
      stronger microbicidal effect than alternating current (maximum reduction log 4.0
      and log 2.9, respectively). The microbiological results of experiments with this
      EAOP prototype revealed higher standard deviations than expected, based on our
      experience with standard water disinfection methods. Safe use of an EAOP system
      requires operating parameters to be defined and used accurately, and thus
      specific monitoring tests must be developed.

PMID- 21902044
TI  - Effect of support and second metal in catalytic in-situ generation of hydrogen
      peroxide by Pd-supported catalysts: application in the removal of organic
      pollutants by means of the Fenton process.
AB  - A catalytic system for the generation of H2O2 from formic acid and oxygen at
      ambient conditions has been developed. Pd-supported catalysts (Pd/C, Pd/TiO2 and
      Pd/Al2O3) have been tested, showing that for bulk purposes Pd/Al2O3 is more
      favourable while for in-situ applications Pd/TiO2 seems to be preferable.
      However, when these catalysts were tested in the in-situ H2O2 generation for the
      oxidation of phenol by means of the Fenton process (in the presence of ferrous
      ion), Pd/TiO2 did not demonstrate the expected results, whereas Pd/Al2O3 showed
      to be an efficient catalyst. Therefore, Pd/Al2O3 is offered as a good catalyst
      for Fenton's reactions with in-situ generated H2O2. In order to optimize the
      operating cost of the process, different initial concentrations of formic acid
      have been tested with Pd/Al2O3, and it has been seen that lowering the initial
      amount of formic acid favours the efficiency of the process. The effect of the
      addition of a second metallic (Pt, Au, Fe, Cu) active phase was studied.
      Concerning H2O2 generation, best results were obtained with a Pd-Au catalyst for
      bulk production (long time) while for in-situ application Pd-Fe showed
      interesting results. The Pd-Fe catalyst also performed similarly to the semi
      heterogeneous Fenton system involving Pd/Al2O3 and ferrous ion in the degradation
      of phenol. Therefore, Pd-Fe catalyst offered an interesting prospect for making a
      full heterogeneous catalyst for Fenton reaction involving in-situ generation of
      H2O2.

PMID- 21902045
TI  - A knowledge-based control system for air-scour optimisation in membrane
      bioreactors.
AB  - Although membrane bioreactors (MBRs) technology is still a growing sector, its
      progressive implementation all over the world, together with great technical
      achievements, has allowed it to reach a mature degree, just comparable to other
      more conventional wastewater treatment technologies. With current energy
      requirements around 0.6-1.1 kWh/m3 of treated wastewater and investment costs
      similar to conventional treatment plants, main market niche for MBRs can be areas
      with very high restrictive discharge limits, where treatment plants have to be
      compact or where water reuse is necessary. Operational costs are higher than for
      conventional treatments; consequently there is still a need and possibilities for
      energy saving and optimisation. This paper presents the development of a
      knowledge-based decision support system (DSS) for the integrated operation and
      remote control of the biological and physical (filtration and backwashing or
      relaxation) processes in MBRs. The core of the DSS is a knowledge-based control
      module for air-scour consumption automation and energy consumption minimisation.

PMID- 21902046
TI  - Long-term effects of the ozonation of the sludge recycling stream on excess
      sludge reduction and biomass activity at full-scale.
AB  - This paper presents a full-scale experience of sludge minimization by means of
      short contact time ozonation in a wastewater treatment plant (WWTP) mainly fed on
      textile wastewater. The WWTP performance over a 3-year operational data series
      was analysed and compared with a two-year operation with sludge ozonation. Lab
      scale respirometric tests were also performed to characterize biomass activity
      upstream and downstream of the ozone contact reactor. Results suggest that sludge
      ozonation: (1) is capable of decreasing excess sludge production by 17%; (2)
      partially decreases both N removal, by lowering the denitrification capacity, and
      P removal, by reducing biomass synthesis; (3) increases the decay rate from the
      typical value of 0.62 d(-1) to 1.3 d(-1); (4) decreases the heterotrophic growth
      yield from the typical value of 0.67 to 0.58 gCOD/gCOD.

PMID- 21902047
TI  - Modelling anaerobic digestion of concentrated black water and faecal matter in
      accumulation system.
AB  - A dynamic mathematical model based on anaerobic digestion model no. 1 (ADM1) was
      developed for accumulation (AC) system treating concentrated black water and
      faecal matter at different temperatures. The AC system was investigated for the
      treatment of waste (water) produced from the following systems: vacuum toilet for
      black water (VBW), vacuum toilet for faeces with urine separation (VF), dry
      toilet (DT), dry toilets for faeces with urine separation (DF), separated faecal
      matter from conventional black water by filter bag (FB). For evaluation of the AC
      system treating the proposed waste (water) sources at 20 and 35 degrees C, two
      options were studied: (1) The filling period of the AC system was constant for
      all waste (water) sources (either 1, 3 or 6 months) and for each period, the seed
      sludge volume was varied; (2) The volume of the AC system was constant for all
      proposed waste (water) sources. The results showed that the filling period of the
      AC system was the main parameter affecting the system performance, followed by
      operational temperature, while the increase of the seed sludge volume slightly
      enhanced the performance of the system. The model results indicated that the
      filling period of the AC system should be higher than 150 days for obtaining a
      stable performance. It was found that the hydrolysis of biodegradable particulate
      chemical oxygen demand (COD) is the rate limiting step, as volatile fatty acid
      concentration is very low in all experimental conditions (< 200 mgCOD/L at 20
      degrees C and < 100 mgCOD/L at 35 degrees C). Based on the results of the two
      options, it was found that the concentrated waste (water) sources have better
      performance than the diluted waste (water) sources, like VBW waste (water).
      Furthermore, smaller volume will be required for the AC system.

PMID- 21902048
TI  - Evaluation of hybrid treatments to produce high quality reuse water.
AB  - Four tertiary hybrid treatments to produce high quality reused water, fulfilling
      Brazilian drinking water regulations, from a slaughterhouse's secondary treated
      effluent were evaluated. The pilot plant with a capacity of 500 L h(-1) was set
      up and consisted of these stages: pre-filtration system (cartridge filter 50
      micron, activated carbon filter, cartridge filter 10 micron), oxidation (H2O2) or
      second filtration (ceramic filter, UF) followed by UV radiation (90 L h(-1)). The
      best combination was T4: pre-filtration followed by H2O2 addition and UV
      radiation (AOP H2O2/UV). Disinfection kinetics by T4 followed pseudo first-order
      kinetics: k(T4) = 0.00943 s(-1) or 0.00101 cm2 mJ(-1). Three different zones (A,
      B, C) were observed in the UV254 degradation kinetics (pseudo-first order
      kinetics): k' decreased over time (k'(A) > k'(B) > k'(C)).

PMID- 21902049
TI  - Sensitivity analysis for the SimpleTreat model to simulate fate of chemicals in
      sewage treatment plants.
AB  - SimpleTreat 3.1 predicts the distribution and elimination of chemicals by sewage
      treatment. The model is used as the default calculation in EUSES 2.0 to estimate
      exposure concentration in the receiving water, soil and air. A sensitivity
      analysis was performed to rank input parameters according to their influence on
      model predictions. Triclosan was selected for the base case. The sewage flow,
      degradation rates and parameters describing the raw sewage were shown to be the
      most sensitive inputs. The pH and dissociation constant are very sensitive
      parameters when working with ionisable compounds. Variation in certain input
      parameters was propagated through the model to yield greater variation in output
      parameters with a maximum ratio of 4.0. SimpleTreat 3.1 is a steady state model
      describing a highly non-steady system. A large variability in the most sensitive
      parameters is expected within a single sewage plant and parameters should
      therefore be selected to cover this variability.

PMID- 21902050
TI  - A fuzzy quality index for the environmental assessment of a restored wetland.
AB  - This paper describes the feasibility study for the restoration of agricultural
      land with a tendency to become waterlogged into a natural wetland, conceived to
      mitigate floods and to remove nutrients from the water drained from the
      cultivated plots. The wetland model, developed in aquatox, includes the nutrient
      dynamics both in the water and in the sediment, and the vegetation that is
      expected to develop as a consequence of flooding. The model inputs were
      synthesized from historical time series of rainfall and chemical data collected
      over the last decade. The model outputs are used to compute a synthetic fuzzy
      quality index (FQI) to assess the removal efficiency of the wetland. This FQI is
      based on three main variables describing the ecosystem quality: chlorophyll-a,
      dissolved oxygen and total suspended solids. This index has the merit of being
      simple enough to be immediately grasped by non-technical people, like managers
      and stakeholders, to whom the restoration project is proposed. The simulations,
      performed under five differing loading scenarios demonstrate the feasibility of
      this solution, which is robust enough to accommodate a 50% increase in either
      nitrogen, phosphorous or organic matter.

PMID- 21902051
TI  - The effect of medium on selected life-history traits in three clones of Lecane
      inermis (Rotifera) from activated sludge.
AB  - We tested the effect of various culture media on life-history traits in three
      clones of the rotifer Lecane inermis, a potential bulking control agent. Four
      types of media were tested: a filtrate of activated sludge, mineral water, and
      each of these media enriched with molasses. The number of live and dead
      individuals and the number of amictic eggs were counted during the 14-day
      experiment, and the egg ratio (ER) and mortality rate were calculated. We found
      that the rotifers were well adapted to the changes in chemical composition of the
      medium and that the addition of molasses resulted in a significant increase in
      rotifer abundance. The highest ER was noted after two days, reaching a maximum of
      4 eggs per female in treatments with filtrate and molasses-enriched filtrate. The
      life-history traits varied depending on the clone and the medium, but all of the
      clones were able to survive and proliferate, even after 14 days of starvation.

PMID- 21902052
TI  - Analysis of build-up of heavy metals and volatile organics on urban roads in gold
      coast, Australia.
AB  - Urban water quality can be significantly impaired by the build-up of pollutants
      such as heavy metals and volatile organics on urban road surfaces due to
      vehicular traffic. Any control strategy for the mitigation of traffic related
      build-up of heavy metals and volatile organic pollutants should be based on the
      knowledge of their build-up processes. In the study discussed in this paper, the
      outcomes of a detailed experimental investigation into build-up processes of
      heavy metals and volatile organics are presented. It was found that traffic
      parameters such as average daily traffic, volume over capacity ratio and surface
      texture depth had similar strong correlations with the build-up of heavy metals
      and volatile organics. Multicriteria decision analyses revealed that that the 1
      74 microm particulate fraction of total suspended solids (TSS) could be regarded
      as a surrogate indicator for particulate heavy metals in build-up and this same
      fraction of total organic carbon could be regarded as a surrogate indicator for
      particulate volatile organics build-up. In terms of pollutants affinity, TSS was
      found to be the predominant parameter for particulate heavy metals build-up and
      total dissolved solids was found to be the predominant parameter for the
      potential dissolved particulate fraction in heavy metals buildup. It was also
      found that land use did not play a significant role in the build-up of traffic
      generated heavy metals and volatile organics.

PMID- 21902053
TI  - A review on the metabolic disorders of iodine deficiency.
AB  - Iodine is in the crucial parts of two hormones of T4 and T3 produced by the
      thyroid glands which are essential for all the aspects of human metabolisms. It
      is demonstrated that iodine deficiency can be considered as sole cause of many
      thyroid abnormalities including mental disorders. Iodine deficiency of sufficient
      degree to cause hypothyroidism during fetus life and early infancy will be
      accompanied with brain abnormality possibly to the stage of mental retardation.
      The iodine deficiency among subjects in their early stage of childhood is not as
      severe as those in their fetus or infancy. In adult subjects the sever iodine
      deficiency can be also associated with mental disorders due to the direct side
      effects of hypothyroidism occurred by lack of iodine. The clinical manifestation
      of iodine deficiency show itself with psychological disorders in adult subjects.
      The status of iodine within blood can be evaluated through measurement of urinary
      iodine level and the low urinary concentration is an indicative of
      hypothyroidism. Mental retardation and brain damage due to iodine deficiency can
      be prevented if iodine supplementation prescribed duly on time.

PMID- 21902054
TI  - The hypocholesterolemic and antioxidative effect of dietary diosgenin and
      chromium chloride supplementation on high-cholesterol fed Japanese quails.
AB  - The current study investigated the effect of natural diosgenin extracted from
      fenugreek seeds, in comparison with the pure standard diosgenin, plus chromium
      chloride (CrCl3) supplementation on high-cholesterol fed Japanese quails. Quails
      were randomly divided into four groups. Group one (n = 25) fed experimental diet
      only (control; contained basal diet supplemented with 1% cholesterol), group 2 (n
      = 20) fed experimental diet supplemented with CrCl3 only (400 microg kg(-1) of
      body weight), groups 3 and 4 (n = 30 per group) were fed experimental diet
      supplemented with either 0.5% (w/w) of extracted diosgenin plus CrCl3 or pure
      standard diosgenin (0.5%) plus CrCl3 respectively, for 12 days. Blood samples
      were collected at days 0 and 12 for measuring levels of lipid profile. The work
      was carried out at Applied Science University and Amman University, Amman, Jordan
      during the period from October 2009 through October 2010. The mean levels of
      total cholesterol (TC) in control quails at d12 was significantly (p < 0.01)
      increased compare to those at d0. Supplementation of diet with CrCl3 alone or
      CrCl3 with diosgenin either extracted or pure standard for 12 days showed a
      significant (p < 0.01) decrease in TC and low density lipoprotein cholesterol
      (LDL-C) levels as compared to those in the control quails. While, high density
      lipoprotein cholesterol (HDL-C) increased significantly (p < 0.01) in quails
      supplemented with diosgenin and CrCl3. At d12, the mean Superoxide Dismutase
      (SOD) activities in erythrocytes of quails in all supplemented groups was
      significantly (p < 0.01) increased as compared to those in control group and was
      more pronounced in erythrocytes of quails supplemented with pure standard
      diosgenin plus CrCl3. These results indicated that the combined diosgenin and
      CrCl3 supplementation to high-cholesterol fed quails might induce a protective
      effect by both regulating lipid and antioxidative damage.

PMID- 21902055
TI  - Growth hormone deficiency in children and adolescents with cerebral palsy:
      relation to gross motor function and degree of spasticity.
AB  - Children with Cerebral Palsy (CP) often have poor linear growth during childhood
      with short final height. Thus, we aimed to assess serum growth hormone (GH),
      insulin like growth factor-1 (IGF-1) and insulin like growth factor binding
      protein-3 (IGFBP-3) levels among CP patients and their relation to each of gross
      motor function and degree of spasticity. Fifty CP children and adolescents were
      studied in comparison to 50 healthy age-, sex- and pubertal stage-matched
      children and adolescents. All subjects were subjected to clinical evaluation,
      Intelligence Quotient (IQ) assessment and measurement of serum GH, IGF-1 and
      IGFBP-3. All auxological and hormonal parameters were significantly lower among
      cases. Fifty two% of cases were GH-deficient and 62% had reduced IGF-land IGFBP-3
      levels. Gross Motor Function Measure- 88 (GMFM-88) score correlated negatively
      with each of basal (r = -0.71, p = 0.02) and peak stimulated GH (r =-0.88, p =
      <0.001); IGF-1 (r = -0.64, p = 0.04) and IGFBP-3 (r = -0.69, p = 0.031). There
      were significant negative correlations between the degree of spasticity assessed
      by Modified Ashworth Scale and each of basal (r = -0.61, p = 0.032) and peak
      stimulated GH (r = -0.78, p = 0.01); IGF-1 (r = -0.65, p = 0.041) and IGFBP-3 (r
      = -0.62, p = 0.035). Growth Hormone Deficiency (GHD) is prevalent in children
      with CP and could be one of the causes of their short stature.

PMID- 21902057
TI  - Antibacterial activity and phytochemical study of six medicinal plants used in
      Benin.
AB  - The ethanol extracts obtained from Psidium guajava, Flacourtia flavescens
      Boswellia dalzielii, Ficus exasperata, Pavetta corymbosa and Hybanthus
      enneaspermus, six species traditionally used in Benin to treat several infectious
      diseases, were evaluated for their in vitro antimicrobial activity against
      Staphylococcus aureus, Enteroccocus feacalis, Escherichia coli and Pseudomonas
      aeruginosa. The minimum inhibitory concentration of extracts was determinate
      using the microplate dilution method. The presence of major phytoconstituents was
      detected qualitatively. The diphenylpicrylhydrazine radical scavenging activity
      was also performed. The extracts exhibited antibacterial activities against the
      tested bacteria. Boswellia dalzielii, Psidium guayava, Pavetta corymbosa and
      Flacourtia flavescens exibited the lowest minimum inhibitory concentration values
      (0.313-2.5 mg mL(-1)). Pseudomonas aeruginosa was the lest sensitive
      microorganism with MIC values higher than 10 mg mL(-1). In antioxidant assay the
      crude extracts of B. dalzielii and P. corymbosa appeared to be as potent as
      quercetol with an inhibition percentage of 83 and 75.3% at 10 microg mL(-1) which
      is comparable to 75.9% for quercetol at the same concentration.

PMID- 21902056
TI  - High vero cell density and rabies virus proliferation on fibracel disks versus
      cytodex-1 in spinner flask.
AB  - To achieve higher titer of rabies virus higher density of host cells will need.
      In this study, capability of FibraCel disks packed in 500 mL spinner basket
      versus Cytodex-1 in 500 mL spinner flask was investigated for propagation of Vero
      cells and PV rabies virus proliferation. Minimal Essential Medium (MEM) + 10%
      Foetal Calf Serum (FCS) and Virus Production- Serum Free Medium (VP-SFM) +4 mM L
      glutamine were used in growth phase and MEM+ 0.2% Bovine Serum Albumin (BSA) and
      VP-SFM were used in virus production phase. Adapted Vero cells grown in VP-SFM
      were used in all SFM experiments while batch and stepwise perfusion modes were
      applied and compared in growth stage. The highest Vero cell density were achieved
      in the trials with 10 g FibraCel disk in stepwise perfusion mode equal to 6.12 x
      10(6) and 5.87 x 10(6) cells mL(-1) in MEM and VP-SFM, respectively while with
      2.73 g Cytodex-1 lower density equal to 4.2 x 10(6) and 4.0 x 10(6) cells mL(-1)
      were achieved. The highest titer of rabies virus and overall virus production
      rate were resulted in VP-SFM and on 10 g disks equal to 2.9 x 10(7) Fluorescent
      Focus Unit (FFU) mL(-1) and 0.14 FFU/Cell/h, respectively versus 1.7 x 10(7) FFU
      mL(-1) and 0.08 FFU/cell/h on cytodex-1 in similar conditions. The second harvest
      of virus was also satisfactory in experiment with 10 g disks (1.7 x 10(7) FFU mL(
      1)) in compare to Cytodex-1 (0.51 x 10(7) FFU mL(-1)). An equal surface area at
      6600 and 12000 cm(-2) were provided in all comparable trials with seeding density
      of 12.5 x 10(3) cells cm(-2). Adapted Vero cells grown in VP-SFM were used in all
      SFM experiments while batch and stepwise perfusion modes were applied and
      compared in growth stage.

PMID- 21902058
TI  - Respiratory bacterial flora from healthy as well as respiratory symptoms'
      subjects.
AB  - Respiratory system is the primary settlement place of opportunistic organisms and
      considered as chief carrier of common respiratory pathogens. The aim of the study
      was to know the opportunistic organisms present in the healthy subjects as well
      as subjects that were suffering from respiratory symptoms. The organisms were
      identified as per standard bacteriological protocol and pathogenicity tests of
      the identified organisms were performed in mouse model. Antibiotic sensitivity of
      the identified organisms was performed. The bacterial flora present in the throat
      swab of apparently healthy as well as subjects suffering from respiratory
      symptoms were: Staphylococcus spp. (39.44%) of which Coagulase positive
      Staphylococcus (21.13%) and Coagulase negative Staphylococcus (18.31%),
      Klebsiella spp. (19.72%), Pseudomonas spp. (15.49%), Proteus spp. (4.23%), E.
      coli (9.86%) and Bacillus spp. (11.27%). Among the isolates Staphylococcus,
      Klebsiella and Pseudomonas were the predominant species. Percentages of
      identified bacteria were higher in respiratory symptoms exhibiting individuals
      (53.52%) than apparently healthy individuals (46.48%). All coagulase positive
      Staphylococcus, Klebsiella spp. and Pseudomonas spp. isolated from respiratory
      symptoms' subjects were found to be pathogenic. The isolated bacteria were
      resistant to amoxicillin and ampicillin but sensitive to ciprofloxacin and
      norfloxacin. Isolated Pseudomonas spp. showed multidrugs resistant properties.
      The study provided information about the pathogenic organisms' present
      respiratory systems of apparently healthy as well as subjects suffering from
      respiratory symptoms. The pathogenic natures of the isolated organisms were
      determined to make aware of scientists as well as clinicians. Antibiotics
      sensitivity assays would provide information to the clinicians for the selection
      of appropriate antibiotics to treat their patients.

PMID- 21902059
TI  - An investigation on different harvesting methods on young pods of KKU # 922 maize
      (Zea mays L.) cultivar for baby corn production.
AB  - This study aimed to search for the best indicator to be used for the harvest of
      maize pods for baby corn production. A Randomized Complete Block Design (RCBD)
      with four replications was used. The treatments are: T1 (Control) Taking sample
      when silks of female flower had extended from tip of pod up to 3 cm long T2,
      silks had extended 1 cm long T3, silks had extended 2 cm long T4, blooming of
      female flower for 2 days T5, blooming of female flowers for 4 days T6, blooming
      of female flower for 6 days T7, one third blooming of male flower T8, two third
      blooming of male flower and T9, full bloom of male flower. Five baby corn
      Characteristics were used i.e., (1) fresh weight of whole ears, (2) fresh weight
      of ears without husk, (3) commercial standard ears, (4) off standard ears and (5)
      disordered kernel-rows of ears. A range of scores from 1 to 9 was applied to
      judge quality and yield in each item of the five baby corn characteristics. A
      score of 1 = the best whilst further increases in scores indicated the decline in
      quality of baby corn. The results showed that an indicator for use in harvesting
      pods of maize for baby corn production was found with T6, i.e. the best time for
      the harvest of pods is when the female flowers had bloomed for 6 days after the
      appearance of silks.

PMID- 21902060
TI  - Immune modulation in response to stress and relaxation.
AB  - Traditional medical science has kept the mind separate from the body. Recently
      people realize the effect of mind on health and psychoneuroimmunology is the new
      evolved science that describes the interactions between psyche and soma. In this
      review through a typical psycho-neuro-endocrino-immune network the effects of
      psychological stress (acute, brief naturalistic and chronic) and relaxation on
      immune modulation has been shown. From this network Corticotrophin Releasing
      Factor (CRF), Adrenocorticotrophic Hormone (ACTH), Glucocorticoids (GC), alpha
      endorphin and Met-enkephalin are found as important endocrine components and T
      cells, B cells, monocytes/macrophages, Natural Killer (NK) cells and their
      cytokines that is Tumor Necrosis Factor-alpha (TNF-alpha), Interferon Gamma (IFN
      alpha) and interleukins such as IL-1, IL-2, IL-4, IL-6, IL-10, IL-12 etc. are
      found as important immune components. Finally, it has been shown that, acute,
      brief naturalistic and chronic stress have different immune modulatory activities
      which are harmful to one's homeostasis and relaxation can help to maintain that
      homeostasis.

PMID- 21902061
TI  - Idiotype/anti-idiotype immunoregulatory network correlates with an improved
      clinical outcome of schistosomiasis mansoni in humans.
AB  - Anti-idiotypes (anti-Ids) have a potential role in the immune modulation of
      various diseases. To study the correlation of anti-Ids with schistosomiasis
      mansoni morbidity, ELISA using polyclonal idiotypes (Ids) was used to determine
      the presence of anti-Ids in sera of 69 patients susceptible and resistant to
      reinfection. Ids were purified against Soluble Worm Antigen (SWAP) from sera of
      New Zealand white rabbits immunized with SWAP. The results showed that anti-Ids
      were detected in 15 (40.5%) of susceptible and 21 (65.6%) of resistant patients.
      Correlation of intensity of infection with age revealed an inverse relationship
      in patients positive for anti-Ids (regression coefficient beta = -0.47, p < 0.05)
      and contrarily, a direct relationship in patients negative for anti-Ids (beta =
      0.67, p < 0.001). In addition, there was a direct association between the
      presence of anti-Ids and the lack of schistosome-related symptoms (chi2 = 3.6, p
      < 0.05) and hepatomegaly (chi2 = 9.4, p < 0.01). Moreover, comparison of patients
      positive and negative for anti-Ids revealed that those negative for anti-Ids were
      more vulnerable to develop symptoms (3.7 times) and hepatomegaly (8.1 times). In
      conclusion, the study further confirms the role of Id/anti-Id regulatory network
      as an important participant in the assortment of an improved clinical outcome of
      schistosomiasis. This may help to formulate a better understanding of the
      mechanisms of protective immunity in humans and provide perspective for the
      development of a future vaccine.

PMID- 21902062
TI  - Effects of salt stress on some nitrogen fixation parameters in faba bean.
AB  - The adverse effects of sea water salinity on number of nodules, nitrogen content,
      nitroginase activity, Chlorophyll a and b content, proline accumulation and
      protein pattern of faba bean plants (Vicia faba commercial cultivar Nubaria 1)
      were investigated. Faba bean plants were irrigated with sea water at 20, 25, 30,
      40 and 50% concentrations and inoculated with rhizobial isolate ARC307 or with
      gamma rays treated isolates namely; ARC1, ARC2, ARC3, ARC4, ARC5, ARC6 and ARC7.
      Nodules number, nitrogen content, nitroginase activity and chlorophyll a and b
      content parameters were decreased by increasing sea water salinity with all used
      isolates, while proline accumulation parameter increased. At the same time, ARC2
      isolate showed the highest values for these parameters above all isolates
      including the parental isolate ARC307 at all studied concentrations except for
      proline accumulation parameter, it was the least. Therefore, ARC2 considered as a
      promising isolate for salt tolerance. Salinity enhanced the occurrence of
      particular novel proteins in faba bean plants infected with ARC2 isolate.

PMID- 21902063
TI  - Characterization of HIV-1 genotypes and antiretroviral drug-resistance mutations
      among patients in Burkina Faso.
AB  - The purposes of this study were: (1) to describe the genetic variability of HIV
      strains found in Burkina Faso, (2) to characterize non-B HIV strains mutation
      profiles selected by ARVs and (3) to detect possible resistances induced by ARV
      drugs. From 30 October 2002 to 20 November 2003, 132 HIV 1-positive patients
      taking Highly Active Antiretroviral Therapy (HAART) for more than one year in
      Bobo-Dioulasso and Ouagadougou were included. T-CD4+ lymphocytes count was done
      using Dynabeads technique while genotypic test and ARV-resistance tests were
      conducted using Pol sequencing that codes for reverse transcriptase reverse,
      integrase and protease. Due to undetectable viremia, 86 samples out of 132 could
      not be characterized. Whereas in the 46 others that had a viral load exceeding
      1000 copies mL(-1), the following HIV-1 subtypes were identified: CRF06 (54,55%);
      CRF02(38,63%); CRF01 (4,55%) and subtype A (2,27%). In addition, several
      mutations related to PI, NRTI and NNRTI resistance were isolated in 27 samples.
      This study found a huge genetic HIV-1 polymorphism in Burkina Faso. The level of
      acquired resistance to ARV after one year of treatment amounted 20.4%. These
      results clearly show that there is imperative need to set up an ARV resistance
      surveillance network in Burkina Faso to guide treatment strategies and follow the
      extension of the phenomenon in the country.

PMID- 21902065
TI  - Estimation of genetic variability in locally grown pulses (Cajans cajan (L.)
      Millsp and Vigna unguiculata (L.) Walp): a panacea for sourcing superior
      genotypes.
AB  - The negligence of breeders and farmers to explore and exploit landraces of pulses
      is worrisome and urgent measures needed to be set in motion to forestall major
      future crisis, taking into cognizance the high adaptability and nutritive values
      accredited to them. This study focused on the estimation of genetic variability
      and heritability of desirable morphological characters in Fiofio (Cajans cajan)
      and Olaudi and Akidi (Vigna unguiculata) with the aim of conservation. Three
      landraces of pulses were sown using randomized complete block design. The field
      experiment was carried out at the University of Calabar Experimental Farm,
      University of Calabar, Calabar, during 2008-2010 growing season. Phenotypic and
      genotypic variances and coefficients of variation and genetic advance were
      estimated on yield and yield-related traits. The results showed that there were
      considerable variations among the pulses for the traits studied. The result
      revealed high genetic variability in the number of leaf per plant, leaf area,
      number of flowers per plant, number of pods per plant and number of seeds per
      plant. It also showed that genetic variability in pod length and 100-seed weight
      was low. Heritability estimates obtained in the result were very high though the
      magnitude of genetic variability in the yield and yield-related traits was not
      proportional to the heritability estimates. The traits studied also show high
      genetic advance. These explicitly showed that there are sufficient genetic
      variations to warrant conservation and improvement in these extinction-threatened
      pulses studied.

PMID- 21902064
TI  - Effect of four different vegetable oils (red palm olein, palm olein, corn oil,
      coconut oil) on antioxidant enzymes activity of rat liver.
AB  - The objective of the study was to evaluate the effect of four different vegetable
      oils [red palm olein (RPO), palm olein (PO), corn oil (CO), coconut oil (COC)] on
      antioxidant enzymes activity of rat liver. Sixty six Sprague Dawley male rats
      which were randomly divided into eleven groups of 6 rats per group and were
      treated with 15% of RPO, PO, CO and COC for 4 and 8 weeks. Rats in the control
      group were given normal rat pellet only while in treated groups, 15% of
      additional different vegetable oils were given. After 4 weeks of treatment the
      catalase (CAT) activity results showed that there was no significance difference
      (p > or = 0.05) between the control group and treated groups while after 8 weeks
      of treatment showed that there was no significant different (p > or = 0.05)
      between control group and RPO group but the treated rat liver with PO, CO and COC
      groups were the lowest and it were significantly lower (> or = 0.05) than control
      group. For superoxide dismutase (SOD) there was no significance difference (p >
      or = 0.05) between the control group and treated groups of vegetable oils after 4
      and 8 weeks of treatment. Thus the study indicated that there was no significant
      (p > or = 0.05) effect on antioxidant enzyme (superoxide dismutase) but there was
      significant effect (p > or = 0.05) on catalase in rat liver.

PMID- 21902066
TI  - Phytochemistry and heamatological potential of ethanol seed leaf and pulp
      extracts of Carica papaya (Linn.).
AB  - This study was aimed at qualitative evaluation of the ethanol seed, leaf and pulp
      extracts of C. papaya for bioactive compounds and also to investigate their
      effect on the haematology in male albino rats. A 3 x 4 factorial experimental
      layout using randomized complete design was adopted. Results show that the
      phytochemicals found in seed, leaf and pulp were almost the same but however, in
      varying proportions. Present result also revealed that there were significant
      effects (p < 0.05) of the extracts on the heamatology of the treated rats, which
      was blamed on the varying and different variants ofbioactive compounds found in
      the extracts they were administered with. Suggestively, C. papaya extracts could
      be used to enhance the production of selected blood parameters, taking issue of
      dosage into consideration.

PMID- 21902067
TI  - Last dispatches.

PMID- 21902068
TI  - Hyper acute stroke unit services.

PMID- 21902069
TI  - The inpatient neurology consultation service: value and cost.
AB  - Neurological conditions comprise a significant proportion of patient admissions
      to hospital but, in the majority of cases, are admitted under the care of non
      neurological physicians. As a consequence, neurological ward consultations are
      commonly requested by the admitting medical teams to review diagnoses and
      management plans. The outcomes of neurological ward consultations were examined
      and the time required for the referral process recorded by performing a detailed
      prospective three-month audit of inpatient referrals to the neurology service.
      The consultations of 120 patients were recorded, categorised and analysed. These
      consultations were beneficial in the vast majority of cases, with a clear impact
      on patient diagnoses or management plans. The consultation process was time
      consuming, however, both in respect of the initial review, but also with follow
      up visits. This audit highlights the importance of neurological input in the
      diagnosis and management of hospital inpatients. The time taken for this process
      should be resourced appropriately.

PMID- 21902070
TI  - Diabetes care during Hajj.
AB  - Keeping well during Hajj is a challenge for people with diabetes. However, with
      proactive planning and education, it may prove to be an excellent opportunity for
      reviewing management and enhancing diabetes education to reduce diabetes-related
      short- and long-term problems. People with diabetes should have enough time to
      consider a management plan. It is important that healthcare professionals are
      well informed regarding the effects of Hajj on diabetes and are able to offer
      advice, guidance and change of medications as required during pre-Hajj
      counselling to enable patients to stay healthy.

PMID- 21902072
TI  - How to write high-quality questions for a high-stakes examination.
AB  - Both the MRCP(UK) written examinations and the specialty certificate examinations
      (SCEs) use single-best-answer questions to assess the knowledge and problem
      solving skills of physicians in training. Since 1999, specialists and senior
      trainees have created large banks of questions for these examinations that cover
      the relevant curricula. Question-writing workshops provide detailed guidance on
      the design of questions that discriminate between candidates of differing
      ability, in a format and a style that aid speed reading and comprehension. Each
      question drafted is subjected to face-to-face peer review and subsequent stages
      of academic scrutiny before reaching the question bank, and later during the
      exacting processes of question selection and standard setting. Feedback to
      question writers at every level of scrutiny helps to support the development of
      question-writing competence, and the analysis of individual question performance
      provides some insight into optimal question design.

PMID- 21902071
TI  - British HIV Association national audit on the management of patients co-infected
      with tuberculosis and HIV.
AB  - This audit aims to compare UK management of tuberculosis (TB)/HIV co-infection
      with recommended practice and to describe local care arrangements. Services
      providing HIV care were invited to complete a survey of care arrangements and to
      review case notes of HIV positive patients aged over 16 who started therapy for
      active TB between October 2007 and April 2008. Corresponding TB services, if
      separate, were invited to complete a similar survey. Responses were received from
      124 of 170 HIV services, and 18 corresponding TB services. Data were obtained for
      236 coinfected patients. Despite some incomplete data, this audit yielded useful
      findings. Many positive smear results were unacceptably delayed. The TB therapy
      completion rate fell short of the chief medical officer's (CMO's) 85% target.
      Culture confirmation of pulmonary TB met the CMO's 65% target. A high number of
      patients were diagnosed with HIV during investigation of TB. Contrary to current
      guidelines, many services do not routinely test TB patients for HIV.

PMID- 21902073
TI  - Changing PACES: developments to the examination in 2009.
AB  - As a consequence of change in medical, educational and regulatory practice,
      MRCP(UK) successfully modified the international PACES examination in 2009. This
      brief paper explains the rationale for change and summarises the development and
      implementation process.

PMID- 21902074
TI  - Development and implementation of the specialty certificate examinations.
AB  - Following successful pilots in 2006, knowledge-based assessments for those
      engaged in specialty training have been developed and implemented in 11 medical
      specialties, by the Federation of Royal Colleges of Physicians in partnership
      with the specialist societies. Over 400 physicians have been involved in a
      project that has required recruitment and training of up to 25 question writers
      in each discipline, and the constitution of examining boards and standard setting
      advisory groups in each specialty. The assessments (now known as the specialty
      certificate examinations) are delivered by computer-based testing in centres
      throughout the UK and overseas. This paper analyses the outcome of 14 examination
      diets, sat by 948 candidates, of whom 72% were occupying UK numbered training
      posts. A total of 786 candidates sat the examination in the UK, 162 in overseas
      centres. Pass rates among UK trainees have generally exceeded 80%, with
      reliability coefficients well in excess of 0.8.

PMID- 21902075
TI  - Dishonesty in the MRCP(UK) Part 1 and Part 2 written examinations: prevention,
      detection and possible remediation.

PMID- 21902076
TI  - The follow-up of renal transplant recipients by telephone consultation: three
      years experience from a single UK renal unit.
AB  - Although telephone consulting is increasingly used by clinicians seeking to
      balance rising caseloads, heightened patient expectation and the desire to ensure
      continued improvements in the quality, convenience and accessibility of the care
      they provide, its use to provide care to renal transplant recipients has not
      previously been described. Climate change is a major global public health threat.
      However, the provision of healthcare itself has a significant environmental
      impact. A transformation to lower carbon clinical care must be achieved without
      detriment to the quality of the patient care. This article reports the use of
      telephone consultation clinics to provide follow-up to renal transplant
      recipients over a three-year period. The benefits of this service to patients,
      providers and the environment are outlined, the existing literature regarding the
      provision of virtual care to patients with kidney disease is reviewed, and the
      possibilities of more widespread adoption are discussed.

PMID- 21902077
TI  - The NHS: assessing new technologies, NICE and value for money.
AB  - The healthcare system in the UK, essentially the NHS, is an open economic system
      subject to the same pressures as any other economic system. The pressures concern
      limited resources coupled with powerful drivers for increasing spending:
      invention, demography and inflation. There have only ever been three types of
      economic system: steady state (everything, as in a feudal system, stays as it was
      the year before), market capitalism (supply and demand are allowed to find their
      own equilibrium) and some version of central planning. In healthcare, most
      advanced countries favour the last of the three. This is for three reasons:
      distribution (not only are the poor less able to pay for sickness, but sickness
      exacerbates poverty), information (markets operate poorly when providers can
      easily outsmart customers) and externalities (it is in the interest of everyone
      that infectious diseases and the other knock-on consequences of ill health are
      ameliorated). So in the UK, the state, with a good deal of cross-party consensus,
      directs most of health service supply. This system has become more complex over
      the decades since the formation of the NHS in 1948. A notable element of the
      complexity is the regulation of the introduction of new technologies. A key
      element of the regulatory system has been the National Institute for Health and
      Clinical Excellence (NICE), and a key aspect of NICE's decisions has been not
      just value, but also value for money. This has not been without controversy.

PMID- 21902078
TI  - Red flags in medical practice.

PMID- 21902079
TI  - Acute liver failure.
AB  - ALF is a multisystem disorder necessitating both predictive and reactive
      management strategies to support and protect organs from the initial and
      subsequent insults encountered. Early referral to a specialist liver centre with
      the option of liver transplantation is recommended. Furthermore, a good
      understanding of the poor prognostic variables is necessary to determine those
      most at risk of developing ALF in order to facilitate timely, safe transfer and
      listing for liver transplantation.

PMID- 21902080
TI  - Dyslipidaemia: integration between primary and secondary care.

PMID- 21902081
TI  - King George III, bipolar disorder, porphyria and lessons for historians.
AB  - In the 1960s, Ida Macalpine and Richard Hunter, mother and son psychiatrists,
      stated that George III's medical records showed that he suffered from acute
      porphyria. In spite of well-argued criticisms by Geoffrey Dean and Charles Dent
      based on their extensive clinical experience of the acute porphyrias, Macalpine
      and Hunter were able to garnish extensive support for their claims from
      historians, psychiatrists, physicians and the media circus and their view is now
      surprisingly widely accepted. Recent research of George III's extensive medical
      records has shown that Macalpine and Hunter were highly selective in their
      reporting and interpretation of his signs and symptoms and that the diagnosis of
      the acute porphyria cannot be sustained. The basis for the false claims and the
      consequences for historians are considered and indicate that there is now an
      opportunity to reassess George III's contributions to events in his reign.

PMID- 21902082
TI  - A rare cause of acute chest pain in a young adult.

PMID- 21902084
TI  - Sleep disturbance and neurological disease.

PMID- 21902083
TI  - Acute systemic lupus erythematosus on the acute medical take: are we missing
      anything?

PMID- 21902085
TI  - Sleep apnoea syndromes and the cardiovascular system.
AB  - Management of SAS and cardiovascular disease risk should be closely linked. It is
      important to screen for cardiovascular disease risk in patients with SAS and vice
      versa. CSA/CSR may be improved by ventilation strategies in heart failure, but
      benefit remains to be proven. For OSA, although CPAP may reduce cardiovascular
      disease risk, its main benefit is symptom control. In the longer-term, CPAP
      should be used alongside standard cardiovascular risk reduction strategies
      including robust weight management programmes, with referral for bariatric
      surgery in appropriate cases. CPAP and NIV should be considered for acute
      admissions with decompensated cardiac failure.

PMID- 21902086
TI  - Insomnia: evidence-based approaches to assessment and management.

PMID- 21902087
TI  - Narcolepsy, idiopathic hypersomnolence and related conditions.

PMID- 21902088
TI  - Obstructive sleep apnoea: relevance to non-sleep clinicians.

PMID- 21902089
TI  - Severe orthostatic hypotension in a diabetic patient may not be due to diabetic
      autonomic neuropathy.
AB  - This lesson describes an unusual case of a man who was recently diagnosed with
      type 1 diabetes and who presented with severe orthostatic hypotension. As his
      diabetes was recent in onset, well controlled, and he had no other signs of
      microvascular disease, other causes of orthostatic hypotension were sought. His
      serum and cerebrospinal fluid were strongly positive for Borrelia burgdorferi
      IgG, suggesting a diagnosis of Lyme neuroborreliosis. Autonomic instability in
      Lyme, while rare, has been previously reported.

PMID- 21902090
TI  - Catastrophic hyperkalaemia following administration of suxamethonium chloride to
      a patient with undiagnosed amyotrophic lateral sclerosis.
AB  - The depolarising neuromuscular blocking agent suxamethonium chloride, frequently
      used during endotracheal intubation, is contraindicated in patients with chronic
      denervation in whom it can cause a life-threatening hyperkalaemic reaction,
      thought to be mediated through upregulation of nicotinic alpha7 acetylcholine
      receptors. An underlying neuromuscular disorder should be considered in all
      patients with acute respiratory insufficiency, and an alternative neuromuscular
      blocking drug must be used if there is any possibility of widespread denervation.

PMID- 21902091
TI  - Isolation in time: a cause of suffering in the elderly. Lessons from Krapp's last
      tape.

PMID- 21902092
TI  - Improving perioperative diabetes care.

PMID- 21902093
TI  - Cardiology a ward rounds: rationale of using a checklist.

PMID- 21902094
TI  - Diagnosis and management of urinary infections in older people.

PMID- 21902095
TI  - Sub-optimal H1N1 vaccine uptake by immunocompromised inflammatory bowel disease
      patients.

PMID- 21902096
TI  - A new year--a new dawn.

PMID- 21902097
TI  - Reform works!

PMID- 21902098
TI  - Unruptured 32-week rudimentary horn pregnancy presenting as right upper quadrant
      pain.
AB  - BACKGROUND: An unruptured third trimester rudimentary horn pregnancy is rare,
      life threatening, and can go undetected until the onset of symptoms. Given the
      high risk of uterine rupture, conservative management after viability is
      controversial. CASE: A 21 year-old with a 32-week rudimentary horn pregnancy,
      diagnosed via exploratory laparotomy five days earlier, presented with acute
      right upper quadrant pain. The patient underwent cesarean delivery. The
      rudimentary horn was noted to be intact, but so thin it was transparent.
      CONCLUSION: Advanced ectopic pregnancy or rudimentary horn pregnancy should be
      considered in cases of unusual or undiagnosed abdominal pain in pregnancy. When
      surgical exploration is performed, an incision allowing optimal visualization and
      exposure is recommended.

PMID- 21902099
TI  - Carotid and vertebral arterial fibromuscular dysplasia masquerading as severe
      preeclampsia: a case report.
AB  - BACKGROUND: Fibromuscular dysplasia is a non-atherosclerotic noninflammatory
      vascular disease that can affect any vascular bed. Dysplasia of the intima,
      media, or adventitia layer of the affected arteries causes stenosis and
      hypertension. Pregnant or post-partum patients may present with hypertension and
      be mistakenly diagnosed with preeclampsia. CASE: A 26 year old Gravida 1 Para 1
      female 20 days post partum from a spontaneous vaginal delivery was transported
      from an outlying facility due to severely elevated blood pressure and transient
      left arm numbness and left sided facial droop. Upon arrival the patient was begun
      on intravenous magnesium sulfate and labetalol for a presumptive diagnosis of
      severe post partum preeclampsia. Her blood pressure and symptoms responded
      promptly. Due to her neurologic symptoms a magnetic resonance angiogram was
      ordered revealing 90% stenosis of her bilateral carotid and vertebral arteries.
      CONCLUSION: Severe hypertension and minimal neurologic symptoms may be the
      presenting symptoms for fibromuscular dysplasia. Cranial imaging is warranted in
      any pregnant or post partum patient who presents with these symptoms to allow
      appropriate treatment.

PMID- 21902100
TI  - Recurrent hematochezia secondary to gastrointestinal stromal tumors (GISTs) in
      neurofibromatosis type one.
AB  - BACKGROUND: Patients with neurofibromatosis type 1 (NF1) suffer from cutaneous,
      neurological and intestinal complications due to the mutation of the
      neurofibromin gene and abnormal protein product. Gastrointestinal stromal tumors
      (GISTs) are relatively rare primary tumors of the stomach and small intestine.
      Patients with NF1 are prone to developing GISTs. We present a case of recurrent
      gastrointestinal (GI) bleeding from multiple GISTs in a patient with NF1. CASE: A
      42 year-old male with NF1 presented with significant GI bleeding; endoscopies
      failed to identify the source. Multiple lesions involving the small bowel were
      seen on laparotomy; he underwent reparative small bowel resection. Pathology
      showed a well circumscribed spindle cell proliferation with minimal atypia and
      rare mitoses; immunostaining was positive for CD117 (KIT) and CD34; KIT mutations
      in exons 9, 11, 13 and 17 were negative. DISCUSSION: Up to 25% of patients with
      NF1 develop GISTs with non-specific presentations; however they may be a source
      of significant GI bleeding. The pathology, course and molecular composition of
      these tumors are different from sporadic GISTs. In NF1, GISTs are usually
      multiple, located in the small bowel (as opposed to the stomach as in sporadic
      cases) and occur at a younger age. Their clinical scenario is not unlike other
      hereditary tumor syndromes-multiple tumors with a 10-20% malignant potential. NF1
      associated GISTs almost uniformly do not exhibit gain-of-function activation of
      KIT or PDGFA (pathogenesis is suggested to be from the loss of heterozygosity of
      the NF1 gene) and are not likely to respond to imatinib. Multiple means of
      localizing GISTs exist and capsule endoscopy should be recommended to all NF1
      patients as it provides a non-invasive approach to localizing the tumors for
      further surgical management.

PMID- 21902101
TI  - Steroid induced spinal epidural lipomatosis--case report and review of the
      literature.
AB  - Steroids are one of the most commonly prescribed medications for a variety of
      medical conditions, often long term. Spinal epidural lipomatosis (SEL) is a state
      of pathological fatty tissue overgrowth in the vertebral canal. It is a rare and
      dangerous complication of chronic steroid therapy that may lead to back pain,
      radiculopathy, or paraparesis. We describe a patient that was taking long term
      steroids and presented with progressively worsening weakness of the lower
      extremities. On the MRI scan, a long segment of unusual accumulation of fatty
      deposits in the posterior aspect of the spinal canal resulting in canal stenosis
      extending from C7 to the T10 level was observed. Despite an appropriate diagnosis
      and surgical intervention, his weakness did not resolve. We discuss the
      implications of this case in the primary care practice.

PMID- 21902102
TI  - Incidental pheochromocytoma: fifteen-year experience at a community hospital.
AB  - BACKGROUND: Pheochromocytoma is a well-recognized neuroendocrine tumor. Classical
      symptoms are well described, but recent studies have suggested that many patients
      are diagnosed incidentally. No studies have evaluated incidental pheochromocytoma
      with respect to year of diagnosis. METHODS: A retrospective study was performed
      from January 1992-November 2006 to evaluate the frequency of incidental
      pheochromocytoma. Patients were included if pathological specimens were
      available. RESULTS: 21 patients were included. 15/21 (71.4%) cases were
      incidentally discovered. 11/15 (73.3%) were diagnosed after 2000, while 4/15
      (26.7%) were diagnosed before 2000. 15/21 (71.4%) patients had hypertension, and
      all 6 patients without hypertension had pheochromocytoma diagnosed incidentally.
      Only 3/21 (14.3%) patients were diagnosed by biochemical testing. DISCUSSION:
      This observational study suggests an increasing number of incidental
      pheochromocytomas. Several possibilities for this observation include increased
      usage of imaging studies, decreased use of biochemical testing, and an increase
      in referring patients to surgeons for resection without an appropriate endocrine
      work-up. Referring physicians and surgeons alike should take note of this.

PMID- 21902103
TI  - Update on fighting tobacco's deadly cost on the poor in West Virginia.

PMID- 21902104
TI  - The skinny on breastfeeding.

PMID- 21902105
TI  - Social media: a communication responsibility.

PMID- 21902106
TI  - Recommended cleaning and processing of flexible otolaryngology endoscopes.

PMID- 21902107
TI  - Communicating with head and neck cancer patients.
AB  - BACKGROUND: Head and neck cancer is only 3 to 5% of all the cancers in the United
      States. The disease causes major changes in the appearance and functional ability
      of patients. PURPOSE: To explore how caregivers communicate with head and neck
      cancer patients who have impaired communication abilities from the disease and
      from treatment. DESIGN: A qualitative grounded theory approach was used. METHODS:
      Thirty-nine caregivers of head and neck cancer patients were recruited from three
      east coast academic-affiliated hospitals with dedicated head and neck cancer
      units. Each person was interviewed, while being audiotaped for 1 1/2 hours. Open
      ended questions were used to elicit comprehensive responses to the issues and
      concerns most important to care for these patients. The tapes were transcribed
      and inputted using Ethnograph v.5. The analysis of the interviews used grounded
      theory methods. Methods to ensure rigor and trustworthiness were incorporated
      into the design. FINDINGS: The results of the data collection revealed the
      majority of participants were women age 47 (average). For most, their beginning
      and highest education was the baccalaureate degree. The entire sample averaged 23
      years in their profession and a more than 15.1 years caring for head and neck
      cancer patients. The sample represented caregivers from primarily the inpatient
      setting, but also included clinic, administrative, research and education. The
      results of the data analysis revealed engaging and distancing behaviors based the
      caregivers' level of comfort. The central topic was communication impairment. The
      core category was "Reading the Patient". The strategies used to identify
      problems, and meet the needs of the patients were "Giving Voice", "Being There",
      "Giving Control", "Saving Face", "Normalizing", "Relieving Pain", and "Giving
      Hope". CONCLUSIONS: A hypothesis emerged from the analysis of the interviews.
      Successfully meeting the physical and psychosocial needs of head and neck cancer
      patients requires an intensive effort and the use of creative methods of
      communication which are primarily self-taught. Much more research needs to be
      done on low and high technology tools to assist caregivers of nonverbal patients
      to meet their needs, including understanding body image change from disfiguring
      facial surgery. The evidenced-based literature is still unavailable to provide
      direction to meet these complex patients' needs. CLINICAL RELEVANCE: This study
      is a beginning effort to identify the complex needs of head and neck patients and
      suggest how to meet these needs. Lessons learned from this study might be applied
      to other patients with impaired communication ability.

PMID- 21902108
TI  - Preventing aspiration in older adults with dysphagia.

PMID- 21902109
TI  - Developing a spirit of inquiry.

PMID- 21902112
TI  - Clinical uses of anticonvulsant drugs other than for epilepsy.

PMID- 21902115
TI  - Medical education.

PMID- 21902114
TI  - Medical education: take 2.

PMID- 21902116
TI  - Fever and renal mass in a young child. Renal abscess.

PMID- 21902117
TI  - An 11-year-old boy with fever.

PMID- 21902119
TI  - Advantages and challenges of social media in pediatrics.

PMID- 21902120
TI  - Anticipatory guidance: making it work for your patients and your practice.

PMID- 21902121
TI  - Enhanced professionalism in pediatric practice.

PMID- 21902122
TI  - Advanced communication strategies for relationship-centered care.

PMID- 21902123
TI  - Quality improvement tools for clinicians.

PMID- 21902124
TI  - Metal-on-metal surface replacement: a triumph of hope over reason: affirms.
AB  - Metal-on-metal hip resurfacing offers some potential for total hip arthroplasty
      (THA) in the young patient. However, short- and intermediate-term results of the
      currently available implants have failed to demonstrate advantage over
      conventional THA. The risks of femoral neck fracture or avascular necrosis have
      been disappointing early limitations of the procedure. The Australian Joint
      Registry reports a 5-year revision rate of all hip resurfacings of 3.8%, compared
      with conventional THAs at 2.8%, and a 9-year cumulative revision rate of 7.2% for
      hip resurfacings. Recent reports of femoral neck erosion and pseudotumors
      associated with resurfacing have raised concern about the survivorship of the
      procedure in some patients. Recently, the British Medicines and Healthcare
      Product Regulatory Agency issued an alert over adverse reactions associated with
      metal-on-metal THAs, with particular concern expressed about hip resurfacings.
      Acetabular bone stock may not be conserved when large-diameter femoral head
      components are used, depending on the surgical technique and implant design. In
      hip resurfacing, the minimum diameter femoral component avoids notching of the
      femoral neck; thus, larger diameter acetabular components may be necessary to
      accommodate the femoral component. Hip resurfacing is contraindicated in cases of
      avascular necrosis of the femoral head, especially with cysts >1 cm in diameter,
      with severe slipped capital femoral epiphysis, and in some posttraumatic
      arthroses; furthermore, the biomechanics of the resurfaced hip appear to be less
      reliably restored than with conventional THA. The hypothesis that resurfacing is
      a more conservative procedure than conventional THA remains unproven at this
      time. Given the documented intermediate failure rates of resurfacing, metal-on
      polyethylene is the more successful implant choice.

PMID- 21902125
TI  - Metal-on-metal surface replacement: a triumph of hope over reason: opposes.
AB  - Hip resurfacing has been performed for over a decade but still raises controversy
      as an alternative to traditional total hip arthroplasty (THA). Concerns exist
      about the potential complications of hip resurfacing, including femoral neck
      fracture and osteonecrosis of the femoral head. Recently, attention has been
      given to the metal-on-metal bearing of hip resurfacing with regard to production
      of metal ions, possible tissue necrosis, and rare instances of metal
      hypersensitivity. Given the success of the gold-standard THA, it is
      understandable why some surgeons believe metal-on-metal surface replacement to be
      "a triumph of hope over reason." However, this article opposes that viewpoint,
      demonstrating that data exist to justify the practice of preserving bone in
      younger patients. Hip resurfacing can maintain femoral bone without the expense
      of removing additional acetabular bone by using modern implants with incremental
      sizing. Furthermore, many of the problems cited with the bearing couple (such as
      excess metal production) have been due to poor implant designs, which have now
      been removed from the market. Finally, we now realize that the metal-on-metal
      articulation is more sensitive to malposition; thus, good surgical technique and
      experience can solve many of the problems that have been cited in the past.
      National registry results confirm that in a select population, hip resurfacing
      performs comparably to THA, while fulfilling the goal of bone preservation.

PMID- 21902126
TI  - Dual poly liner mobility optimizes wear and stability in THA: affirms.
AB  - A dual-mobility acetabular component consists of a large, fixed, porous-coated
      acetabular component and a bipolar femoral component. These components are often
      called tripolar components. This configuration provides a stable, well-fixed
      implant platform against bone and 2 articular interfaces, a large polyethylene
      surface directly apposed to a highly polished metal implant, and a standard-sized
      (28- or 32-mm) femoral head captured within polyethylene. The dual-mobility cup
      appears to offer a safe, effective, durable solution to hip instability. The
      concept has extensive laboratory and clinical support. Although the long-term
      durability of these implants is unknown, the tested wear rates of a dual-mobility
      design with the current generation of highly cross-linked polyethylene are
      significantly lower than any previously reported wear rates. The recently
      introduced modular dual-mobility shell offers surgeons substantial flexibility in
      addressing the issue of hip instability with a cost-efficient, familiar option.

PMID- 21902127
TI  - Dual poly liner mobility optimizes wear and stability in THA: opposes.
AB  - Total hip arthroplasty (THA) is an effective intervention for the treatment of
      arthrosis with excellent survivorship. Nonetheless, dislocation and osteolysis
      remain significant complications. A dual-mobility acetabular component has been
      advocated to improve stability and wear. Stability is imparted by increasing the
      effective femoral head size, which allows a larger range of motion (ROM) before
      neck-socket impingement occurs. Increasing ROM, however, introduces an additional
      problem of bony impingement of the trochanter against the pelvis. Consequently,
      there is little improvement in ROM for heads >36 to 40 mm. A 0.4% incidence of
      instability at the larger articulation has been reported in primary THA using the
      dual-mobility liner, which is equivalent to reports for conventional THA. The
      dual-mobility liner has introduced the unique complication of intraprosthetic
      dislocation, where the femoral head dissociates at the smaller articulation as a
      result of polyethylene wear. An incidence of intraprosthetic dislocation of 3.6%
      has been reported, which far exceeds dislocation of conventional arthroplasty.
      The dual-mobility liner is a monoblock acetabular component without the capacity
      for augmented bony fixation. Inability to achieve primary stability has been
      reported as high as 18% and therefore its usefulness in revision THA is
      questionable. Proponents of the dual-mobility liner cite improved wear
      characteristics over conventional THA; however, few studies support this
      proposition. Retrieval studies have reported that the dual-mobility liner does
      not avoid wear or osteolysis. Theoretically, it is inconceivable that wear would
      be diminished with an additional articulation with a huge surface area, where the
      differential hardness has been reversed to a soft-on-hard bearing.

PMID- 21902128
TI  - The posterior approach in THR: assuring capsular stability.
AB  - Repair of the posterior capsule is advocated to reduce dislocation after total
      hip replacement (THR). To date, no predictable physical findings are reported in
      the literature to assess the capsular integrity and risk of hip dislocation after
      the posterior approach. The internal rotation test is performed at 4 to 6 weeks
      postoperatively with the hip and knee flexed at 90 degrees  while the patient is
      supine. The test is positive if a firm endpoint is felt with internal rotation of
      <=15 degrees . Between January 2007 and January 2008, twenty-three patients who
      had magnetic resonance imaging (MRI) at a mean 1.8+/-0.7 years after posterior
      approach THR were included in this study. Magnetic resonance images were reviewed
      by a blinded radiologist for the integrity of the posterior capsule and
      quadratus, the distance between the piriformis and conjoined tendon to bone, and
      the amount of piriformis obturator internus atrophy. Magnetic resonance imaging
      results in patients with positive internal rotation tests showed an intact
      posterior capsule and scarring of the tendons with no severe muscle atrophy. In
      patients with a negative internal rotation test, MRI showed incomplete healing of
      the tendons and severe muscle atrophy. Sensitivity and specificity of the
      internal rotation test for tendon/scar healing were 100% and 93%, respectively.
      The internal rotation test is a simple, reproducible test that, if positive, has
      a high correlation with capsule/tendon healing.

PMID- 21902129
TI  - Anterior approach in THA improves outcomes: affirms.
AB  - In general, the literature makes numerous positive claims regarding the direct
      anterior approach with a fracture table for total hip arthroplasty (THA),
      including quicker recovery and return to unassisted ambulation, along with
      reduced soft tissue damage, surgery time, pain, and risk of dislocation with
      early elimination of hip precautions. The benefits of the direct anterior
      approach are mostly due from muscle preservation rather than muscle splitting,
      which occurs with the more traditional approaches. With the use of the muscle
      preserving direct anterior approach for THA, there is less muscle damage and
      earlier return to function, and postoperative precautions are not needed. The
      most significant improvements in THA have been allowing patients to be
      immediately weight bearing as tolerated after THA, incorporating a multimodal
      pain management protocol, and now using the direct anterior approach. There is a
      learning curve, and I strongly recommend that people attend cadaver-based
      learning centers as well as surgeon visitations. We must always remember the oath
      we took to "do no harm," especially when embarking on a new procedure such as the
      direct anterior approach in THA or any other new procedure or technology. My
      position in the debate is not whether we should embrace this technique or other
      new techniques, but rather how they should be introduced.

PMID- 21902130
TI  - Anterior approach in THA improves outcomes: opposes.
AB  - Total hip arthroplasty (THA) can be performed through multiple surgical
      approaches, including anterior, anterolateral, lateral, transtrochanteric,
      posterolateral, posterior, and the 2-incision technique. The overwhelming
      majority of THAs today are performed through a posterolateral approach, which has
      many advantages: it can be extended without difficulty, it is expeditious, it
      results in reduced blood loss and little muscle damage, and recovery is rapid.
      The major disadvantage of the approach is its increased dislocation rate, which
      has become less of a problem with the advent of larger femoral heads and dual
      mobility acetabular components. The anterior approach is another hip approach
      with advantages and disadvantages. One disadvantage is the need for a special
      table on which to perform the procedure, which can cost >=$100,000. Many surgeons
      also recommend the use of intraoperative fluoroscopy with this approach, which
      prolongs surgery and adds possible draping contamination during the fluoroscopy.
      Exposure of the femur may be difficult with this approach, especially in patients
      with increased body mass index. The operative time also tends to be longer with
      this approach, as exposure may be more tedious. The published data report
      significant complications with this procedure.

PMID- 21902131
TI  - Cemented femoral fixation: the North Atlantic divide.
AB  - In the United Kingdom, more cemented than cementless stems are implanted, whereas
      in North America, few cemented stems are implanted. This is primarily because
      cemented stems have not performed well in North America, whereas they have in the
      United Kingdom, as different designs have been used. The majority of cemented
      stems used in the United Kingdom are polished, collarless, and tapered. These are
      forgiving, as they subside within the cement mantle and compress the cement and
      stabilize the interface. They perform well in both young and active patients and
      elderly patients. They also do well in osteoporotic bone, with deformity, or with
      suboptimal cementing techniques. As the position of the stem can be varied, it is
      simple to achieve appropriate leg length, offset, and version. Cement can be used
      to deliver antibiotics locally. If revision is necessary, it is relatively
      straightforward. Cement has numerous advantages that outweigh the main
      disadvantage of an extended operating time.

PMID- 21902132
TI  - Stubby stems: good things come in small packages.
AB  - Standard-length porous-coated tapered femoral stems perform exceedingly well in
      primary total hip arthroplasty (THA) at long-term follow-up. Nevertheless, there
      are multiple reasons to strongly consider the relatively new concept of short
      tapered stems. First, there is already a wide variation in the lengths of
      "standard" components and the ideal length is unknown. The goal of tapered stems
      is to load the proximal femur, and shortened stems accomplish this task. Second,
      while the distal extension may help prevent varus, unlike cemented stems, which
      are failure-prone with varus alignment, tapered designs are not. Additionally,
      elimination of the distal extension may reduce potential stress shielding. Third,
      short stems obviate problems with proximal-distal mismatch, excessive femoral
      bowing, diaphyseal deformities, and preexisting hardware. Fourth, implantation of
      smaller components requires less violation of bone and soft tissue, facilitating
      less invasive surgical approaches and favorable revision settings if necessary.
      Fifth, in comparison to hip resurfacing and other unconventional short-stem
      designs, tapered stems are familiar to most orthopedic surgeons and do not incur
      a steep learning curve. Finally, our early experience with this implant in 1750
      THAs since 2006 has been excellent. In a series of >650 THA, compared to standard
      length tapered stems, the short stem had equivalent clinical outcome scores,
      significantly fewer femoral fractures (12/389 [3.1%] vs 1/269 [0.4%]), and only 1
      (1/269 [0.4%]) femoral revision (infection) at 2-year follow-up. Short stems
      represent the logical progression of a proven precedent in standard-length
      tapered stems.

PMID- 21902133
TI  - Minimizing infection risk: fortune favors the prepared mind.
AB  - Despite advances in care, infection in total joint arthroplasty remains a serious
      problem that has yet to be solved. Reported infection rates range from <0.5% in
      highly specialized centers to a high of 2% as reported at a national level. The
      epidemiology of total joint arthroplasty remains challenging because of the
      relatively low, but significant, incidence of infection. Still, there are
      variables that can be addressed that have demonstrated evidence regarding
      reduction in infection rates. These variables include optimizing medical
      conditions in the preoperative period such as anemia, blood glucose, and
      nutrition. In the perioperative period, administration of parenteral antibiotics
      within 1 hour of incision is a must. The effect of the operating room environment
      is less clear, but it is evident that traffic flow in the operating room has a
      negative effect on infection rates. Skin preparation with chlohexidine is now the
      agent of choice, and evidence exists that iodophor impregnated occlusive
      dressings add value. Razors should not be used. Surgical staples for closure have
      an increased risk of superficial infection as compared to subcuticular sutures.
      In the postoperative period, early, persistent wound drainage should be managed
      aggressively. There is no evidence to support the use of parenteral antibiotics
      past 24 hours in routine cases. Patients should be advised about prophylaxis for
      infection when undergoing dental work and other high-risk procedures. There is a
      strong movement to extend this prophylactic period indefinitely, as opposed to 2
      years postoperatively. Finally, and perhaps most importantly, it is the surgeon's
      responsibility to be aware of all these issues and to strongly advocate for
      patient safety in ensuring that infection risk is minimized.

PMID- 21902134
TI  - Treating abductor deficiency: a transference technique.
AB  - Loss of abduction power is a common problem after total hip arthroplasty (THA)
      and may lead to severe limp and instability. A surgical reconstruction technique
      using a gluteus maximus flap transfer was developed to repair deficient abductor
      muscles and capsule. The gluteus maximus muscle was split as in a posterior
      approach to the hip, and the anterior portion of the muscle was elevated as a
      flap, separating it from the fascia lata and fashioning a triangular distal
      fascial end. The lateral surface of the greater trochanter was decorticated, and
      the anterior half of the gluteus maximus was sutured to the greater trochanter
      with multiple nonabsorbable sutures through drill holes in the bone. The distal
      fascial end was sutured beneath the vastus lateralis muscle with heavy absorbable
      sutures. The posterior portion of the gluteus maximus (approximately one-sixth of
      the muscle body and half the length) was passed beneath the primary flap to
      substitute for the gluteus minimus and capsule. The tensioning of the flap was
      done with the hip in 15 degrees  to 20 degrees  abduction to ensure adequate
      tension in the transferred muscle. The lower half of the gluteus maximus muscle
      and fascia lata were also closed over the greater trochanter and transferred
      muscle flap with the hip abducted and then closed proximally, leaving the
      anterior edge of the gluteus maximus flap unsutured so that the transferred
      muscle would be allowed to pull directly on the greater trochanter. Gradual
      rehabilitation included 2-handed support for 8 weeks and careful gradual
      abduction exercises beginning 4 weeks postoperatively.

PMID- 21902135
TI  - Use of a barbed suture in the closure of hip and knee arthroplasty wounds.
AB  - Wound closure in primary and revision total hip and knee arthroplasty is an
      essential and critical component of the procedure. A well-performed closure may
      take up to 20 to 30 minutes for primary and revision surgeries, respectively.
      Traditionally, a layered closure is performed using various forms of absorbable
      and nonabsorbable sutures placed in an interrupted fashion, requiring the surgeon
      to tie knots to secure each stitch. Disadvantages of knot tying include increased
      operative time, prominence in subcutaneous layers, and local tissue ischemia.
      Recently, a bi-directional, barbed suture has been introduced that affords
      surgeons the ability to close soft tissue layers in a running fashion without the
      need for knot tying. The bi-directional nature of the barbs allows for
      simultaneous closure from the wound center, therefore offsetting the increased
      cost per suture by the decreased number of sutures used and the time saved in the
      operating room to close the incision. Additional potential advantages of using
      knotless sutures include enhanced biomechanical strength, increased resistance to
      catastrophic arthrotomy failure, and a more watertight closure. Our early data
      support the efficiency and safety of using this suture in total joint
      arthroplasty wound closure. This article reviews our experience and describes the
      technique for using barbed sutures during wound closure in 940 cases of primary
      and revision total joint arthroplasties.

PMID- 21902136
TI  - The dislocator, early and late: the 3 am phone call.
AB  - Hip dislocation is one of the most common causes of patient and surgeon
      dissatisfaction following hip replacement. To correctly treat dislocation, the
      causes must first be understood. Patient factors include age older than 70 years,
      medical comorbidities, female sex, musculoligamentous laxity, revision surgery,
      issues with the abductors and trochanter, and lack of education. Issues related
      to the surgeon and technique are surgical volume and experience, surgical
      approach and repair, adequate restoration of femoral offset and leg length,
      correct component position, and avoidance of soft tissue or bony impingement.
      Chief among implant-related factors is the design of the head and neck region. Is
      the femoral head diameter sufficient, and, in concert with the prosthetic neck,
      is there an adequate head-neck ratio? Skirts on longer neck lengths greatly
      reduce the head-neck ratio and should be avoided if possible. There must be
      available offset choices to restore soft tissue tension. Lipped liners aid in
      gaining stability, yet may result in impingement and dislocation if improperly
      placed. Late dislocation may result from polyethylene wear, soft tissue
      destruction, trochanteric or abductor disruption and weakness, or infection.
      Understanding the causes of hip dislocation allow prevention in a majority of
      instances. Proper preoperative planning includes the identification of high
      offset patients in whom inadequate restoration of offset will reduce soft tissue
      tension and abductor efficiency. Component position must be accurate to achieve
      stability without impingement. Finally, patient education cannot be
      overemphasized, as most dislocations occur early and are preventable with proper
      instructions.

PMID- 21902137
TI  - The pseudo A(LT) periprosthetic fracture: it's really a B2.
AB  - Periprosthetic fracture of the proximal femur involving the lesser trochanter
      (the Vancouver type A(LT)) is an uncommon occurrence. As it is basically an
      avulsion fracture of the attachment of the iliopsoas, it does not destabilize the
      stem and can be treated nonsurgically. In contrast, there is a so-called type
      "new B2" periprosthetic fracture of the lesser trochanter, which includes a
      segment of the proximal medial femoral cortex. This is usually seen within 6
      weeks of the index procedure, typically following insertion of a tapered,
      cementless stem within a demineralized femur. This may be due to an unrecognized
      intraoperative fracture that subsequently displaced under load, or it may occur
      soon after, during rehabilitation. It is important to distinguish this fracture
      from the type A(LT), because it is associated with destabilization of the stem
      and requires early reintervention. The principles of treatment depend on the
      timing of the fracture and the size of the medial fracture fragment. If
      recognized intraoperatively as a nonpropagated cortical crack, then extraction of
      the broach or stem followed by cerclage cable fixation and reinsertion of the
      stem is adequate in most cases, with protected weight bearing for 6 weeks. If
      diagnosed postoperatively, or if the fracture fragment is larger, then management
      with a stem that gains fixation distal to the fracture is required. This
      distinction between the pseudo type A(LT) and the type "new B2" is important to
      recognize if appropriate treatment is to be prescribed and a satisfactory outcome
      is to be assured.

PMID- 21902138
TI  - Cancellous impaction grafting in femoral revision THA.
AB  - Options in the management of the deficient femur during revision hip arthroplasty
      include cemented or cementless fixation. The results with cemented femoral
      revision have not been historically successful. While the use of extensively
      coated implants in revision total hip arthroplasty has been more uniformly
      excellent, issues, such as thigh pain, stress shielding, and lack of bone stock
      restoration, have been raised. Impaction grafting in revision hip arthroplasty is
      an attempt to reconstitute bone stock and avoid problems associated with
      excessively large or long uncemented stems. The original concept of impaction
      grafting was promoted by Slooff and applied to the femur by Gie and Ling. While
      originators' results were promising, issues, such as fracture and poor graft
      delivery, were noted. Modifications to the original technique were recently
      described by Howie, which used longer stems when necessary, as well as an
      improved graft delivery system. We report our results with 30 consecutive hips
      using this method. At follow-up, 3 patients were known to have died, leaving 27
      for evaluation. Two of the 27 were failures: 1 recurrence of infection and 1
      loose stem. The remaining 25 were clinical successes with bone stock restoration
      in all and no periprosthetic fractures. We believe that impaction grafting
      remains a viable option for the management of the severely deficient femur in
      whom cementless fixation methods are questionable.

PMID- 21902139
TI  - The results of TKA: what the registries don't tell us.
AB  - National registries have provided valuable feedback to surgeons and improved
      patient care by decreasing revision rates and identifying defective or poorly
      performing devices. Although there have been thousands of peer review
      publications in the literature, significant gaps exist in relevant knowledge
      relating to performance of hip and knee devices due to shortcomings in many
      published studies. Most studies come from specialty centers and may not reflect
      the results that can be expected from devices in widespread use. Sample sizes are
      frequently small, and studies are underpowered to draw major conclusions or to
      stratify data based on clinically important variables. National registries
      effectively address many of these problems, but also have shortcomings. Registry
      data are now being used to promote specific devices, which opens the door to
      potential abuse of this information. While device design can impact implant
      survival, other factors, such as surgical technique, surgeon, hospital, patient
      factors, and even country, may have far more impact on revision rate than implant
      design. Revision rates often differ among different designs by as little as 5% to
      10% while these previously mentioned factors can result in differences in
      revision rate and order of magnitude higher. Failure to control these numerous
      other potentially confounding variables can lead to false or misleading
      conclusions. In general, registries are far more effective in identifying poorly
      performing devices that manifest in clusters of failures than in identifying
      small differences in performance among relatively well-designed devices. It is
      important for surgeons interpreting data generated from registries to be aware of
      potential pitfalls of these data as well as their value.

PMID- 21902140
TI  - Distal femoral varus osteotomy: unloading the lateral compartment: long-term
      follow-up of 45 medial closing wedge osteotomies.
AB  - Distal femoral medial closing wedge osteotomy is useful for mechanical axis
      realignment to unload the lateral compartment of the valgus knee. The primary
      indication for unloading the lateral compartment is lateral unicompartmental
      osteoarthritis. Alternative treatment options include lateral unicompartment or
      total knee arthroplasty (TKA). Prerequisites for the osteotomy include a 90
      degrees  arc of motion, age younger than 60 years, and an active patient capable
      of an extensive period of rehabilitation. Surgery is carried out through a
      midline skin incision and uses a subvastus approach. The medial femoral closing
      wedge osteotomy is fixed with a 90 degrees  dynamic compression blade plate. A
      critical technical point is the need to insert the blade plate parallel to the
      joint line. The right angle plate corrects the tibialfemoral angle to 0 degrees .
      A benefit of the closing wedge over an opening wedge osteotomy is reduced risk of
      nonunion. Survivorship and functional outcome of 41 patients with 45 distal
      femoral varus osteotomies at a mean follow-up of 13.3 years were retrospectively
      analyzed. Survivorship at 10, 15, and 20 years was 90%, 79%, and 21.5%
      respectively. Mean Modified Knee Society Score was 36.1 preoperatively, 74.4 at 1
      year postoperatively, and 60.5 at last follow-up. Distal femoral varus osteotomy
      is effective at unloading the lateral compartment in unicompartmental arthritis
      in the valgus knee. It may be indicated in the young, high activity demand, and
      overweight patient. By 20 years after the osteotomy most patients require
      conversion to TKA.

PMID- 21902141
TI  - Mosaicplasty.
AB  - Management of the patient with symptomatic full-thickness chondral or
      osteochondral defects of the knee presents a challenging problem for the
      orthopedic surgeon. The natural history of untreated lesions demonstrates
      progressive degenerative changes and deterioration in functional outcome scores.
      Medical management, osteotomies, lavage, and debridement procedures temporize
      symptoms and slow progression. Cartilage restoration procedures such as
      microfracture and cell-based therapies have shown promise, but there are concerns
      of the long-term durability of these procedures in the active population.
      Mosaicplasty allows for restoration of articular defects with hyaline cartilage,
      and has shown excellent durability. Articular defect should measure between 1 to
      4 cm(2) in diameter and extend 10 mm into subchondral bone. Mosaicplasty can be
      challenging when attempted arthroscopically, and the threshold to convert to an
      open procedure should be low when adequate visualization is not achieved. Use of
      variable graft size maximizes defect fill with hyaline cartilage. Avoidance of
      graft prominence >1 mm and attention to the contour of the joint optimizes the
      recreation of articular surface. This is achieved by placing central grafts in a
      large defect slightly prouder to obtain a convex shape to the articular surface.
      With attention to the nuances of the surgical technique, mosaicplasty offers an
      excellent option for cartilage restoration in the young active patient.

PMID- 21902143
TI  - TKA sans tourniquet: let it bleed: opposes.
AB  - The literature supports the routine use of a tourniquet during total knee
      arthroplasty (TKA). With tourniquet use, there is decreased intraoperative blood
      loss with subsequent improved visibility and a bloodless surgical field. This
      facilitates efficiency with the potential for decreased operating time. Increased
      operating time has been associated with an increase in the incidence of infection
      after TKA. Opponents of routine tourniquet use cite rare or theoretical concerns.
      Multiple authors have concluded that the incidence of deep vein thrombosis is not
      related to using a tourniquet. The rare events of muscle dysfunction or nerve
      injury are transient. Peripheral vascular disease, in which patients have no
      palpable distal pulses, should be considered a possible contraindication to the
      use of a tourniquet during TKA. If tourniquet time and pressure are respected
      during TKA, we believe the benefits outweigh the perceived and theoretical
      concerns.

PMID- 21902142
TI  - Does preoperative patellofemoral joint state affect medial unicompartmental
      arthroplasty survival?
AB  - One contested contraindication to medial unicompartmental knee arthroplasty (UKA)
      has been status of the patellofemoral joint. Surgeons have avoided UKA when the
      patellofemoral joint has radiographic evidence of arthritic changes. However,
      recent studies advocate ignoring patellofemoral joint status when considering
      UKA. The purpose of this study was to compare the failure rate of mobile-bearing,
      medial UKA in patients with and without preoperative radiographic evidence of
      patellofemoral joint degeneration. Preoperative radiographs from a random
      selection of 503 patients (638 knees) treated with UKA for anteromedial
      osteoarthritis were assessed by an observer blinded to clinical outcome. The
      patellofemoral joint was graded using the modified Altman classification from 0
      to 3 with 0 being no evidence of changes and 3 being severe, and identified 396
      grade 0, 168 grade 1, 65 grade 2, and 9 grade 3 knees. At 1- to 7-year follow-up,
      there have been 17 revisions for overall survivorship of 97.3%. Kaplan-Meier
      analysis predicted 97.9% survival in knees with patellofemoral joint disease and
      93.8% survival in knees without patellofemoral joint disease at 70 months (P=.1).
      Failure requiring revision occurred in 3.5% (14/396) of grade 0 knees, 1.2%
      (2/168) of grade 1, 1.5% (1/65) of grade 2, and 0% (0/9) of grade 3. No survival
      difference was noted between knees with medial or lateral patellofemoral joint
      disease (P=.1). No knees were revised for progression of disease in the
      patellofemoral joint or anterior knee pain. In light of this investigation and
      the work of others, preoperative radiographic changes in the patellofemoral joint
      can be safely ignored when considering patients for medial UKA without
      compromising survivorship.

PMID- 21902144
TI  - Results of prospective, randomized clinical trials comparing standard and high
      flexion posterior-stabilized TKA: a focused review.
AB  - High-flexion total knee arthroplasty (TKA) designs have been available for
      several years for patients desiring a greater postoperative flexion. We conducted
      a focused review on published results of prospective, randomized clinical trials
      that compared a standard posterior-stabilized TKA with a high-flexion posterior
      stabilized TKA design. Follow-up ranged from 1 to 2.7 years. None of the articles
      included in the review showed a statistical difference between the standard and
      high-flexion designs in clinical flexion or range of motion. Mean postoperative
      flexion ranged from 106 degrees  to 130 degrees  for the standard design and 110
      degrees  to 128 degrees  for the high-flexion design. Based on currently
      available literature, high-flexion cruciate-substituting TKAs do not appear to
      provide increased flexion in the short term. The downsides of these designs, such
      as increased cost, increased bone resection, and early femoral loosening, need to
      be weighed against the potential long-term improvement in polyethylene wear due
      to increased conformity in high flexion. Continued follow-up to document these
      findings will be important.

PMID- 21902145
TI  - Neutral mechanical alignment: a requirement for successful TKA: affirms.
AB  - Restoration of an overall neutral mechanical axis has been a long-held tenet in
      total knee arthroplasty (TKA). Numerous biomechanical, finite element, and
      clinical studies have demonstrated that coronal malalignment, particularly varus,
      is associated with increased strain, higher failure rates, and, in some cases,
      poorer outcomes. With advances in computer-assisted navigation, 3-dimensional
      imaging, and patient-specific positioning guides, the potential for greater
      precision in bone resection and component positioning has rekindled interest in
      this important issue. Several recently published studies demonstrating no
      difference in survivorship for malaligned TKAs have challenged the concept of an
      alignment safe zone. Some surgeons have discussed a paradigm shift in defining
      optimal alignment. While we agree that compared to several decades ago, there is
      greater understanding of TKA kinematics and that broad targets for alignment may
      not impart significant benefit as a dichotomous variable, there are multiple
      reasons why neutral alignment and classic bone cuts remain valid and important in
      delivering a successful TKA. In comparison to the preponderance of evidence
      advocating a neutral mechanical axis and approximately 5 degrees  to 7 degrees 
      valgus anatomic alignment, there is insufficient support for reasonably choosing
      any other target. Although technology has improved surgical precision, it has not
      eliminated the human factor, and aiming for neutral provides the safest margin
      for error. The foremost objective of TKA is a durable and well-functioning joint,
      not necessarily one that replicates normal or the patient's native condition.
      While the latter goal is certainly desirable, the priority of the former should
      never be overlooked.

PMID- 21902146
TI  - Neutral mechanical alignment: a requirement for successful TKA: opposes.
AB  - There is increasing evidence that for a number of patients, neutral alignment is
      not normal. Patients with so-called constitutional varus have been in varus
      alignment since the end of their growth. Restoring neutral alignment in these
      cases may not be the best option for these patients since it is abnormal to them.
      We recently performed a number of observational studies to find out how patients
      develop constitutional varus, how these patients can be recognized, and which
      factors contribute. A cohort of 800 young patients was analyzed to determine the
      influence of activity level on growth and the development of lower-leg alignment.
      At the same time, 250 asymptomatic adults between 20 and 27 years were analyzed
      to determine the incidence of constitutional varus. The results showed that 32%
      of adult men and 17% of adult women had constitutional varus knees with a natural
      mechanical alignment >=3 degrees  varus. Constitutional varus was associated with
      increased sports activity during growth and began to become apparent at the time
      of growth spurt. Based on these data, we believe that an important fraction of
      the normal population has a natural alignment at the end of growth of >=3 degrees
      varus. This may be a consequence of Hueter-Volkmann's law. Restoration of
      mechanical alignment to neutral in these cases therefore may not be desirable and
      in fact unnatural for them.

PMID- 21902147
TI  - Multiple needle puncturing: balancing the varus knee.
AB  - The so-called "pie crusting" technique using multiple stab incisions is a well
      established procedure for correcting tightness of the iliotibial band in the
      valgus knee. It is, however, not applicable for balancing the medial side in
      varus knees because of the risk for iatrogenic transsection of the medial
      collateral ligament (MCL). This article presents our experience with a safer
      alternative and minimally invasive technique for medial soft tissue balancing,
      where we make multiple punctures in the MCL using a 19-gauge needle to
      progressively stretch the MCL until a correct ligament balance is achieved. Our
      technique requires minimal to no additional soft tissue dissection and can even
      be performed percutaneously when necessary. This technique, therefore, does not
      impact the length of the skin or soft tissue incisions. We analyzed 61 cases with
      varus deformity that were intraoperatively treated using this technique. In 4
      other cases, the technique was used as a percutaneous procedure to correct
      postoperative medial tightness that caused persistent pain on the medial side.
      The procedure was considered successful when a 2- to 4-mm mediolateral joint line
      opening was obtained in extension and 2 to 6 mm in flexion. In 62 cases (95%), a
      progressive correction of medial tightness was achieved according to the above
      described criteria. Three cases were overreleased and required compensatory
      release of the lateral structures and use of a thicker insert. Based on these
      results, we consider needle puncturing an effective and safe technique for
      progressive correction of MCL tightness during minimally invasive total knee
      arthroplasty.

PMID- 21902148
TI  - Why knees fail in 2011: patient, surgeon, or device?
AB  - The outcome of total knee arthroplasty (TKA) is influenced by multiple
      interconnected factors, including patient selection, implant design, and surgical
      technique. Total knee arthroplasty has been shown to be highly successful, with
      patient satisfaction rates reported from 85% to 95% with low rates of failure,
      but if failure occurs, its impact is significant. In 2003, 402,000 primary TKAs
      and 32,000 revision TKAs were performed in the United States, and the number of
      TKAs is expected to double by 2015. Recent data on modern implant designs and
      techniques have demonstrated a surprising number of early failures, although the
      true number of early failures is unknown. Patient medical comorbidities should be
      optimized preoperatively, while psychosocial issues and workers compensation are
      more nebulous yet contribute greatly to patient perceived outcomes. Understanding
      current failure mechanisms of primary TKA and how to prevent complications will
      be critical to help manage a potentially overwhelming TKA revision burden. This
      article discusses failure rates as well as factors from the patient, surgeon, and
      device, that contribute to TKA failure.

PMID- 21902149
TI  - Wound healing problems in total knee arthroplasty.
AB  - It is important to avoid underestimating the significance of wound complications
      following total knee arthroplasty (TKA). Expedient and aggressive care is
      recommended. Understanding the blood supply to the skin around the knee and
      measures to prevent wound complications are fundamental to preventing wound
      problems. A detailed patient history and physical examination will identify high
      risk patients and any modifiable risk factors. Operative techniques such as
      raising full-thickness skin flaps and judicious placement of skin incisions in
      the presence of pre-existing scars can greatly reduce the incidence of wound
      problems. The first step in treating wound problems is recognizing when a problem
      is present and knowing when a minor problem can turn into a major one.
      Superficial infections or stitch abscesses can be treated with conservative
      treatment. However, the surgeon should have a low threshold to revert to surgical
      management if drainage persists. Skin necrosis or non-viable skin must be excised
      in the operating room, and the presence of a deep infection must be diagnosed by
      joint aspiration. The appropriate course of action in dealing with deep infection
      is dependent on the duration elapsed since the index procedure. The ability to
      perform a medial gastrocnemius muscle flap and skin graft is an invaluable skill
      in complex cases where primary wound closure cannot be achieved. Meticulous
      attention to detail during surgery and aggressive surgical treatment of wound
      complications can be the difference in saving the knee.

PMID- 21902150
TI  - Instability in primary total knee arthroplasty.
AB  - Instability is one of the most common causes of failure of total knee
      arthroplasty (TKA). The presentation can vary from pain to frank dislocation with
      the etiologies just as varied. Instability after TKA can be classified by where
      the instability occurs in the knee's arc of motion as well as the chronicity of
      the problem. Acute instability is related to intraoperative injuries or excessive
      release of important coronal stabilizers such as the medial collateral ligament
      in extension or the posterolateral corner in flexion. Chronic instability in
      extension is often related to varus/valgus malalignment. Chronic instability in
      flexion can be related to an undersized femoral component, excessive tibial
      slope, or excessive elevation of the joint line affecting the isometry of the
      collateral ligaments in midflexion. Recurvatum instability is a rare complication
      that often coincides with extensor mechanism dysfunction or neuromuscular
      disorders. When addressing instability after TKA, it is critical to determine the
      root cause of the problem as well as evaluate for other causes of pain such as
      infection or aseptic loosening. When revision surgery is warranted, it should
      follow the basic principles of restoring a neutral mechanical alignment, setting
      the appropriate component rotation, balancing the flexion and extension spaces,
      and restoring the height of the native joint line.

PMID- 21902151
TI  - The efficacy of multimodal high-volume wound infiltration in primary total hip
      replacement.
AB  - Multimodal wound infiltration with local anesthetics, adrenaline, and
      nonsteroidal anti-inflammatory agents can lower the opiate intake, reduce the
      length of stay, and enhance early mobilization after total hip arthroplasty
      (THA). A retrospective review of 204 patients undergoing primary THA was
      undertaken. One hundred two patients had their wounds infiltrated with
      ropivacaine, adrenaline, and ketorolac by the operating surgeon intraoperatively.
      Subsequently, a 19-gauge wound catheter was inserted percutaneously into the hip
      joint. Patients received 2 further top-up doses of 20 mL of ropivacaine (7.5
      mg/mL) at 10 and 20 hours postoperatively. These patients were compared to a
      control group of 102 patients who received no local infiltration. Both groups
      were comparable in terms of body mass index and age. Opiate consumption in the
      first 48 hours after surgery and length of hospital stay were recorded. The mean
      consumption of morphine in the treatment group was 42.3 mg (standard deviation
      [SD], 31.2 mg) compared to 60.9 mg (SD, 33.8 mg) in the control group (P<.0001).
      The mean length of stay was significantly reduced from 5.2 days (SD, 1.6 days) in
      the control group to 4 days (SD, 1.3 days) in the treatment group (P<.0001). The
      time needed by the patients to walk for 3 meters after surgery was significantly
      reduced in the treatment group (median, 25 vs 46.1 hours; interquartile range,
      20.7- 45.1 vs 27.2- 50.9; P<.0001). This is the largest series to demonstrate
      that a multimodal perioperative wound infiltration technique in primary THA
      surgery leads to early attainment of immediate postoperative rehabilitation
      milestones and reduced length of stay along with reduction in postoperative
      opiate consumption.

PMID- 21902152
TI  - Experimental study on phase-contrast imaging with synchrotron hard X-ray for
      repairing osteonecrosis of the femoral head.
AB  - Synchrotron radiation light is 1 of 4 artificial light sources, the others being
      electric light, X-ray, and laser. Phase-contrast imaging with hard X-ray has
      achieved wide application in many scientific fields, such as biomedicine and
      material science. This article compares the effectiveness of
      nanohydroxyapatite/collagen (nHAC) and autologous mesenchymal stem cell for the
      repair of defects in a rabbit model with osteonecrosis of the femoral head under
      the monitoring of phase-contrast imaging with synchrotron hard X-ray. We
      established models of bilateral osteonecrosis of the femoral head defect using
      New Zealand rabbits and divided them into 3 groups. Imaging techniques such as
      phase-contrast imaging and diffraction enhanced imaging with synchrotron hard X
      ray were applied to assess the degradation and repair process of nHAC and
      mesenchymal stem cell at 4, 8, and 12 weeks postoperatively. We found phase
      contrast imaging with synchrotron hard X-ray displayed the reparative process of
      the bone defect, degradation of nHAC, and osteocyte substitution. There were
      significant differences in the repair of the bone defect and osteogenesis in
      groups B and C compared with group A (control). Osteogenesis was more significant
      in group C. We provided experimental data for the development and application of
      synchrotron hard X-ray imaging techniques and concluded that phase-contrast
      microimaging with synchrotron hard X-ray displays the reparative process of bone
      tissue at a micro-level and plays an important role in the development of tissue
      engineering.

PMID- 21902153
TI  - Factors predicting health-related quality of life in knee osteoarthritis among
      community-dwelling women in Japan: the Hizen-Oshima study.
AB  - Knee osteoarthritis is the most common chronic joint disorder in elderly people.
      However, a population-based, longitudinal study on health-related quality of life
      in knee osteoarthritis has not been conducted in Japan. We studied 333 women aged
      50 years and older at baseline, with 8 to 9 years of follow-up. Anteroposterior
      weight-bearing knee radiographs were obtained at baseline and graded according to
      the Kellgren-Lawrence criteria. Definite osteoarthritis was defined as Kellgren
      Lawrence grade 2 or higher in at least 1 joint. At baseline, all participants
      were asked if they had knee pain and comorbidities (heart disease, lung disease,
      stroke, or diabetes mellitus). Height (m), weight (kg), and chair stand time were
      measured. At follow-up, quality of life in knee osteoarthritis was evaluated
      using the Japanese Knee Osteoarthritis Measure score. Multiple linear regression
      analysis showed that age, knee osteoarthritis, knee pain, comorbidity, and
      increasing chair stand time were independently related to subsequent health
      related quality of life. These findings suggest that treating knee osteoarthritis
      and comorbidities, managing pain, and optimizing lower extremity muscle strength
      may be effective targets for intervention.

PMID- 21902154
TI  - Primary total joint arthroplasty performed in operating rooms following cases of
      known infection.
AB  - No study has examined infection rates in "clean" cases following "dirty" cases.
      This study evaluated patients undergoing elective primary total joint
      arthroplasties performed in operating rooms following cases of known infection
      for development of postoperative infection. A retrospective review of all
      elective primary total joint arthroplasties performed over a 5-year period at our
      institution was conducted. Patients who underwent primary total joint
      arthroplasties that followed cases of known infection in the same operating room
      were examined (minimum follow-up of 1 year) to determine the occurrence of
      infection based on culture data and subsequent procedures. Thirty-nine total
      joint arthroplasties (27 total knee arthroplasties and 12 total hip
      arthroplasties) in 35 patients were performed following cases of known infection
      in the same operating room. Of these patients, 1 (2.6%) developed a
      periprosthetic joint infection. The infecting organism (Propionibacterium acnes)
      was the same as that isolated from the preceding "dirty" case. Further
      investigation is necessary to determine whether performing primary total joint
      arthroplasties immediately following "dirty" cases increases risk of infection.

PMID- 21902155
TI  - Is repetitive intraoperative splash basin use a source of bacterial contamination
      in total joint replacement?
AB  - Splash basins are used in arthroplasty cases to wash instruments. Several studies
      in the literature have shown these basins being a potential source of bacterial
      infection. This study assesses the risk of contamination of intraoperative splash
      basins used to wash and store instruments. A total of 46 random clean primary
      arthroplasty cases (32 hips, 13 knees, and 1 unicondylar knee) were studied by
      taking cultures of sterile splash basins as soon as they are opened (controls)
      and again at wound closure after instruments and debris have come into contact
      with the sterile water. All cultures were taken with sterile culture swabs and
      sent to the laboratory for aerobic, anaerobic, and fungal culture. Outcome
      measured was any positive culture. A total of 92 cultures from 46 cases were
      tested. Only 1 (2.17%) control culture, which grew Streptococcus viridans, was
      positive for bacterial growth. One of 46 samples (2.17%) taken at wound closure
      was positive for coagulase-negative Staphylococcus. Mean time between basin
      opening and wound closure was 180+/-45 minutes. For the 1 infected sample taken
      at the conclusion of the case, it was 240 minutes. Previous studies show
      contamination rates as high as 74% for splash basins used intraoperatively. Our
      study contradicts the belief that splash basins are a high source of infection,
      with only 2.17% of basins showing contamination. Splash basins can be a potential
      source of contamination, but the risk is not as high as previously cited in the
      orthopedic literature.

PMID- 21902156
TI  - An analysis of the hip and knee reconstruction section of the orthopaedic in
      training examination.
AB  - This article analyzes the hip and knee reconstruction section of the Orthopaedic
      In-Training Examination (OITE). All of the hip and knee reconstruction questions
      from 2005 to 2009 were analyzed, and the following data were recorded: number of
      questions per year in the hip and knee section, total number of questions on the
      OITE per year, national average score by year in training, references cited,
      taxonomy classification of each question, topics that were tested, imaging
      modalities used for a given question, and treatment modalities tested. Eight
      percent to 9% of the questions on the OITE each year were hip and knee
      reconstruction-related questions. Performance improved with each year in
      training, but not by a statistically significant amount. The most commonly tested
      topics over the past 5 years were anatomy and physiology, ligament and/or gap
      balancing during total knee arthroplasty (TKA), surgical approaches, properties
      of polyethylene, periprosthetic fractures about an arthroplasty, and questions
      dealing with the mechanical properties of implants. In 4 out of 5 years, the
      majority of questions were classified as Taxonomy 1 (knowledge and recall). The
      bulk of the questions each year did not require the examinee to interpret a
      radiograph or make a treatment decision. The most common references cited were
      from Journal of Bone and Joint Surgery (American), followed by the Journal of
      Arthroplasty. This detailed analysis of the hip and knee reconstruction section
      of the OITE should improve resident performance, and may serve as a study tool
      for the OITE.

PMID- 21902157
TI  - Acromioclavicular joint pain in patients with adhesive capsulitis: a prospective
      outcome study.
AB  - Diagnosis of adhesive capsulitis is a clinical diagnosis based on history and
      physical examination. Afflicted patients exhibit active and passive loss of
      motion in all planes and a positive capsular stretch sign. The effect of adhesive
      capsulitis on acromioclavicular biomechanics leading to tenderness has not been
      documented in the literature. This study reports on the incidence of
      acromioclavicular tenderness in the presence of adhesive capsulitis. Furthermore,
      we note the natural history of such acromioclavicular joint pain in relation to
      that of adhesive capsulitis. Over a 2-year period (2005-2007), 84 patients
      undergoing initial evaluation for adhesive capsulitis were prospectively examined
      with the use of validated outcome measures and physical examination.
      Acromioclavicular joint tenderness results were compared and analyzed on initial
      evaluation and final follow-up of at least 1 year. Forty-eight patients (57%)
      with adhesive capsulitis had acromioclavicular joint pain on examination. At
      final follow-up, as range of motion improved, a significant increase in American
      Shoulder and Elbow Surgeons/Penn shoulder score and decrease in number of
      patients with acromioclavicular pain was noted with only 6 patients with residual
      pain (P<.05). In the presence of adhesive capsulitis, there is not only
      compensatory scapulothoracic motion but also acromioclavicular motion. This often
      results in transient symptoms at the acromioclavicular joint, which abate as the
      frozen shoulder resolves and glenohumeral motion improves. This is important to
      recognize to avoid unnecessary invasive treatment of the acromioclavicular joint
      when the patient presents with adhesive capsulitis.

PMID- 21902158
TI  - Long-term effectiveness of Sorbie-QUESTOR elbow arthroplasty: single surgeon's
      series of 15 years.
AB  - With increasing usage of many types of total elbow replacements, there is a
      continuing need for clinical series that report survivorship, complications and
      revisions, and performance of single types of implants over extended time
      periods. The purpose of this study was to assess the long-term effectiveness of
      all implants of the Sorbie-QUESTOR (SQ) unlinked surface arthroplasty conducted
      by a single surgeon (C.S.) over 15 years at a single site, and to determine
      whether there were diagnostic group differences. Between 1995 and 2002, 51 S-Q
      prosthetic elbows were implanted into 44 patients. The patient groups were
      hemophilia, rheumatoid arthritis, and "other," which included osteoarthritis,
      traumatic arthritis, psoriatic arthritis, and reactive arthritis. Annual
      evaluations included scores of pain, range of motion, and function. The most
      recent annual evaluation was included in the data set. Details of complications
      and revisions were recorded. The hemophiliac group had the best survival outcomes
      at 87.5%. Eighteen prostheses required revision or removal with all but 3
      retained or replaced. Postoperatively, 73% rated their pain as 'slight' or
      'none'. The hemophilia and rheumatoid arthritis groups made very large total
      flexion/extension gains. The rheumatoid arthritis group made significant forearm
      motion gains. Average functional assessment gains were nearly 2 grades of 5
      functional levels and were significant for all groups. The S-Q surface
      arthroplasty has demonstrated long-term effectiveness in patients with a variety
      of elbow joint pathologies showing reduction in pain, large gains in joint range
      and function, and good long-term survival.

PMID- 21902159
TI  - Intraoperative ultrasound assistance for excision of impalpable musculoskeletal
      soft tissue tumors.
AB  - Intraoperative ultrasonography is a useful tool for the detection and extirpation
      of liver metastases, breast masses, and melanoma. However, the efficacy of this
      technology in intraoperative localization and resection of small soft tissue
      tumors has not been addressed. The purpose of this study is to report on the
      efficacy of intraoperative ultrasound assistance in excising impalpable
      musculoskeletal soft tissue tumors. Twenty-two soft tissue tumors <3 cm (range,
      0.7-3 cm) were resected with intraoperative ultrasound assistance. All tumors
      were localized in the deep panniculus, fascia, or muscle. Surgical time and
      length of incisions was recorded in all the cases. Intra- and postoperative
      reregistration was made to confirm the tumor resection. Ultrasound assistance was
      successful in obtaining an accurate localization in all treated cases. Mean
      surgical time was 30 minutes (range, 13-87 minutes). Average incision length was
      5.7 cm (range, 2.5-10.6 cm). Reregistration allowed intraoperative confirmation
      of the adequacy of the excision. The procedure allowed recognized and excised
      additional nodules not previously diagnosed in 3 cases. Postoperative echography
      done in all patients confirmed complete extirpation of the tumors, and
      histopathology confirmed adequate margins obtained. Intraoperative ultrasound can
      be used as an efficient tool to localize and treat impalpable small soft tissue
      tumors.

PMID- 21902160
TI  - Teriparatide (rh [1-34] PTH) improved osteointegration of a hemiarthroplasty with
      signs of aseptic loosening.
AB  - Incidences of osteoporosis and fragility fractures are constantly increasing,
      which are associated with increased morbidity and mortality. When these patients
      undergo surgery, a higher number of postoperative complications may be expected
      because of poor bone quality and delayed healing. As a result, poorer primary
      stability of the implant, initial loosening, and impaired fixation strength in
      different regions may be seen. In these patients, we can choose the most advanced
      implants, but it is necessary to stimulate bone biology to increase the stability
      of the implant. This article reports the result obtained in a patient diagnosed
      with osteoporosis with aseptic loosening of a hip hemiarthroplasty after
      treatment with teriparatide (rh [1-34] PTH). This drug is indicated for the
      treatment of osteoporosis in men and postmenopausal women with high fracture risk
      and glucocorticoid-induced osteoporosis, and is administered subcutaneously for 2
      years. It has an anabolic effect through stimulation of the osteoblast population
      that increases trabecular connectivity, cortical thickness, and bone mineral
      content. In animal models, teriparatide improved implant fixation 2 to 4 weeks
      after administration, resulting in the thickening of bone trabeculae and
      increased bone mass in the peri-implant area. In this retrospective analysis of
      clinical data and radiographic and scintigraphic images, after 24 months of
      treatment, the patient experienced clinical improvement associated with the
      disappearance of radiographic signs of loosening and a decrease in pathological
      radiotracer uptake in the bone scan, which are signs of osteointegration after
      treatment with teriparatide.

PMID- 21902161
TI  - Recurrent hemarthrosis after unicompartmental knee arthroplasty.
AB  - Recurrent hemarthrosis after knee arthroplasty can be disabling, requiring
      adequate and immediate diagnosis and treatment for recovery of symptoms and joint
      function. The most commonly reported cause is impingement of proliferative
      synovium between prosthetic components. Although various procedures for
      hemarthrosis have been reported after knee arthroplasty for patients who do not
      respond to conservative treatment, the recommended first-line therapy is open
      surgery or embolization. Although hyperplastic synovium was observed during the
      first and second arthrotomy, in our case, tissue impingement was not detected. We
      describe a rare case of recurrent hemarthrosis after unicompartmental knee
      arthroplasty (UKA) and successful treatment by open synovectomy. A 66-year-old
      woman presented with spontaneous osteonecrosis of the medial femoral condyle in
      the right leg. She underwent UKA of the right knee of the medial condyle.
      Eighteen months after UKA, the patient developed recurrent hemarthrosis. Open
      arthrotomy was performed 22 months after UKA, revealing only hematoma with no
      obvious hemorrhage or loosening of the prosthesis. No history of trauma or use of
      anticoagulant medications was present. After a symptom-free period of 8 months,
      another 2 episodes of hemarthrosis occurred over the course of 8 months. A second
      open arthrotomy was performed. Hyperplastic synovium with fibrin and hemosiderin
      pigmentation was observed, again without hemorrhage or loosening. There were no
      pathological features of pigmented villonodular synovitis. Synovectomy was
      performed, and no hemarthrosis has recurred for 2 years.

PMID- 21902162
TI  - Subacromial osteochondroma.
AB  - The most common cause of impingement syndrome is mechanical irritation of the
      subacromial bursa and rotator cuff by the coracoacromial arch. Offending
      structures include the undersurface of the anterolateral acromion, coracoacromial
      ligament, and the undersurface of the distal clavicle. We present a case of
      impingement syndrome caused by mechanical irritation of the rotator cuff by a
      subacromial osteochondroma that was successfully treated with arthroscopic
      resection. Osteochondroma is the second most common benign bone tumor following
      nonossifying fibroma. These lesions are thought to arise from aberrant growth of
      normal epiphyseal growth plate cartilage. Ninety percent of osteochondromas arise
      from the metaphyseal regions of long bones (eg, distal femur, proximal tibia, or
      proximal humerus). Scapular involvement accounts for 3.0% to 4.6% of all reported
      osteochondromas. These lesions represent 14.4% of all tumors of the scapula and
      49% of benign scapular tumors, making them the most common benign bone tumors of
      the scapula. Our patient failed nonoperative management of his subacromial
      osteochondroma. The concern for malignant transformation was low, as the
      patient's pain had been consistent for the past 15 years. Although his pain had
      been largely unchanged for more than a decade, he elected to undergo resection so
      that he could resume the hobbies that his pain had forced him to abandon. He
      reported substantial pain relief and restoration of function following
      arthroscopic resection and subacromial decompression, reinforcing mechanical
      irritation of the rotator cuff as the source of his shoulder pain and
      dysfunction. To our knowledge, this is the first report of arthroscopic resection
      of a subacromial osteochondroma.

PMID- 21902163
TI  - Acute compartment syndrome of the forearm secondary to infection within the space
      of Parona.
AB  - The deep midpalmar space of the hand communicates with the space of Parona in the
      forearm. Infection of these deep spaces can be difficult to diagnose. This
      article presents the first reported case of acute compartment syndrome of the
      forearm secondary to infection within the space of Parona. This article discusses
      the anatomy of the space of Parona, highlighting its communicating spaces and the
      importance of recognizing a deep-space infection of the hand as a possible cause
      of compartment syndrome of the forearm. This article also suggests a method of
      clinical examination to aid in the diagnosis of infection within the space of
      Parona to allow more specific planning of surgical intervention through early
      decompressive surgery, with surgical exploration to exclude and drain infection
      when no other clear cause for the rise in pressure within the osteofascial
      compartment is apparent.

PMID- 21902164
TI  - Robotic guidance in total hip arthroplasty: the shape of things to come.
AB  - Surgeons want to perform a perfect total hip arthroplasty (THA) with every
      operation. Human performance has limitations, especially when performing a
      mechanical operation in a biological environment. Recent suggested changes to
      improve outcomes have been large femoral heads and anterior incisions, but
      unfortunately, neither has resulted in any scientific data that change has been
      effected. The scientific data tell us that poor component positions and
      impingement are the source of increasing mechanical complications. Therefore,
      attempts have been made to improve the surgeon's performance by precise
      quantitative knowledge in the operating room. Robotic-guided navigation provides
      numerical data for cup inclination plus anteversion and center of rotation;
      femoral leg length and offset; and combined anteversion of the cup and stem. The
      acetabular bone preparation is done with a reamer connected to a robotic arm,
      which prevents human error by the surgeon of reaming off line or too deep. This
      technology provides predictable and reproducible results.

PMID- 21902165
TI  - A lateral approach to lower eyelid entropion repair.
AB  - The authors describe a simple technique that highlights the use of the sagittal
      anatomy of the lower eyelid to aid identification of the retractors during
      involutional entropion repair. This anatomy is exposed following lateral
      canthotomy and inferior cantholysis. The orbital septum is seen to enclose the
      fat pad and fuse with the retractors above it prior to insertion into the tarsus.
      The septum, orbicularis, and skin are incised from the lateral approach, allowing
      exposure of the retractors for tarsal reattachment, and the procedure is
      completed with a lateral tarsal strip. Forty-eight procedures in 42 patients with
      involutional entropion were performed using this technique and 90% and 89% of
      primary and recurrent entropion, respectively, were successfully repaired. Mean
      operating time was 30 minutes. The lateral approach to a standard procedure for
      entropion repair can reduce operating time and technical difficulty.

PMID- 21902167
TI  - Outcomes of 25-gauge pars plana vitrectomy in the surgical management of
      proliferative diabetic retinopathy.
AB  - BACKGROUND AND OBJECTIVE: To report outcomes and complications of 25-gauge pars
      plana vitrectomy (PPV) for patients with complications of proliferative diabetic
      retinopathy (PDR). PATIENTS AND METHODS: Retrospective, interventional,
      consecutive case series of 174 eyes undergoing primary 25-gauge PPV for PDR from
      2006 to 2009. Primary outcomes were visual acuity changes and rates of
      postoperative complications. RESULTS: Visual acuity improved from 20/187 before
      to 20/69 after surgery (P < .0001). Postoperative vitreous hemorrhage occurred in
      38.7% of eyes and 10.4% of all eyes required another PPV for non-clearing
      vitreous hemorrhage. Complications included limited choroidal effusion (5.2%),
      rhegmatogenous retinal detachment (4.6%), hypotony, rubeosis, and ocular
      hypertension (4.1%), neovascular glaucoma (2.3%), hyphema (1.2%), and phthisis
      bulbi (0.6%). CONCLUSION: The authors found 25-gauge PPV to be effective for
      vitreous removal and membrane dissection. The spectrum and frequency of
      complications were similar to those reported for 20-gauge PPV for PDR. In the
      surgical management of PDR, 25-gauge PPV is an alternative.

PMID- 21902166
TI  - Pulse-encoded ultrasound imaging of the vitreous with an annular array.
AB  - The vitreous body is nearly transparent both optically and ultrasonically.
      Conventional 10- to 12-MHz diagnostic ultrasound can detect vitreous
      inhomogeneities at high gain settings, but has limited resolution and
      sensitivity, especially outside the fixed focal zone near the retina. To improve
      visualization of faint intravitreal fluid/gel interfaces, the authors fabricated
      a spherically curved 20-MHz five-element annular array ultrasound transducer,
      implemented a synthetic-focusing algorithm to extend the depth-of-field, and used
      a pulse-encoding strategy to increase sensitivity. The authors evaluated a human
      subject with a recent posterior vitreous detachment and compared the annular
      array with conventional 10-MHz ultrasound and spectral-domain optical coherence
      tomography. With synthetic focusing and chirp pulse-encoding, the array allowed
      visualization of the formed and fluid components of the vitreous with improved
      sensitivity and resolution compared with the conventional B-scan. Although
      optical coherence tomography allowed assessment of the posterior vitreoretinal
      interface, the ultrasound array allowed evaluation of the entire vitreous body.

PMID- 21902168
TI  - Successful outcomes of 25- and 23-gauge vitrectomies for giant retinal tear
      detachments.
AB  - BACKGROUND AND OBJECTIVE: The authors examined the feasibility of performing 25-
      and 23-gauge micro-incision vitrectomy surgery (MIVS) for a giant retinal tear.
      PATIENTS AND METHODS: The medical records of 12 eyes of 11 patients with giant
      retinal tear who underwent MIVS using perfluorocarbon liquids were reviewed. All
      patients were observed for at least 6 months postoperatively. RESULTS: An
      intraoperative re-attachment was achieved in 12 eyes (100%) and 11 eyes (92%)
      remained attached without intraocular tamponade. Silicone oil was used in 9 of 12
      eyes and removed 2 weeks after the initial vitrectomy except in one eye. The
      postoperative retinal complications included macular pucker in two eyes,
      subretinal perfluorocarbon liquid in two eyes, retinal folds in one eye, cystoid
      macular edema in one eye, and redetachment due to proliferative vitreoretinopathy
      in one eye. CONCLUSION: Although the study had a short follow-up period, primary
      MIVS appears to be safe and feasible for giant retinal tear surgery.

PMID- 21902169
TI  - Effect of dissolved oxygen changes on activated sludge fungal bulking during lab
      scale treatment of acidic industrial wastewater.
AB  - The cloning and sequencing of fungal 18S rRNA genes followed by the
      identification of filamentous fungal species by fluorescent in situ hybridization
      (FISH) and the enumeration of filamentous fungal cells by flow cytometry-FISH (FC
      FISH) were used to investigate the effect of dissolved oxygen (DO) changes on
      activated sludge (AS) fungal bulking during a lab-scale treatment of acidic
      industrial wastewater. By increasing DO levels from < .5 to > 2 mg L-1, bulking
      started to occur due to the outbreak of fungal filaments, whereas the chemical
      oxygen demand (COD) removals sharply increased from < 40 to > 70%. Clone library
      analyses revealed that all clonal fungal sequences were of yeast origin, and that
      only one and four yeast species were individually detected in AS at two DO
      levels. Subsequent FISH identification of filamentous yeast species within
      bulking sludge using self-designed oligonucleotide probes suggested that all
      probe-reactive cells of Trichosporon asahii had a filamentous morphology and were
      the dominating filamentous microorganism in the AS. The FC-FISH analyses of
      bacteria and two main yeast species showed that the DO shift resulted in a sharp
      increase of T. asahii, by a factor of 48-60, which caused filamentous yeast
      bulking. Subsequently, the restoration of DO levels to <0.5 mg L-1 effectively
      restored the sludge settlement and yeast community, as well as unacceptable COD
      removals.

PMID- 21902170
TI  - Gold- and iodine-mediated internal oxygen transfer of nitrone- and sulfoxide
      functionalized alkynes.
AB  - Intramolecular oxygen transfer of nitrone- and sulfoxide-alkynes was achieved
      using a catalytic amount of Au(I) and a stoichiometric amount of iodine. The
      Au(I)-catalyzed cyclization of a nitrone-terminal alkyne afforded a cyclic
      iminoester, while cyclization of analogous nitrone-internal alkynes yielded
      aldehyde-enones. The I(2)-mediated cyclization of nitrone-alkynes afforded
      iodinated gamma-lactams and the I(2)-mediated internal redox of the closely
      related sulfoxide-alkynes gave diketones functionalized with a thoiether.

PMID- 21902171
TI  - Antibacterial surfaces based on polymer brushes: investigation on the influence
      of brush properties on antimicrobial peptide immobilization and antimicrobial
      activity.
AB  - Primary amine containing copolymer, poly(N,N-dimethylacrylamide-co-N-(3
      aminopropyl)methacrylamide hydrochloride) (poly(DMA-co-APMA)), brushes were
      synthesized on Ti surface by surface-initiated atom transfer radical
      polymerization (SI-ATRP) in aqueous conditions. A series of poly(DMA-co-APMA)
      copolymer brushes on titanium (Ti) surface with different molecular weights,
      thicknesses, compositions, and graft densities were synthesized by changing the
      SI-ATRP reaction conditions. Cysteine-functionalized cationic antimicrobial
      peptide Tet213 (KRWWKWWRRC) was conjugated to the copolymers brushes using a
      maleimide-thiol addition reaction after initial modification of the grafted
      chains using 3-maleimidopropionic acid N-hydroxysuccinimide ester. The modified
      surfaces were characterized by X-ray photoelectron spectroscopy (XPS), water
      contact angle measurements, attenuated total reflectance Fourier transform
      infrared (ATR-FTIR) spectroscopy, atomic force microscopy (AFM), and ellipsometry
      analysis. The conjugation of the Tet213 onto brushes strongly depended on graft
      density of the brushes at different copolymer brush compositions. The peptide
      density (peptides/nm(2)) on the surface varied with the initial composition of
      the copolymer brushes. Higher graft density of the brushes generated high peptide
      density (pepetide/nm(2)) and lower number of peptides/polymer chain and vice
      versa. The peptide density and graft density of the chains on surface greatly
      influenced the antimicrobial activity of peptide grafted polymer brushes against
      Pseudomonas aeruginosa.

PMID- 21902172
TI  - Impedance characteristics and polarization behavior of a microbial fuel cell in
      response to short-term changes in medium pH.
AB  - pH oppositely influences anode and cathode performance in microbial fuel cells.
      The differential electrochemical effects at each electrode and the resultant full
      cell performance were analyzed in medium pH from 6.0 to 8.0. Potentials changed 
      60 mV/pH for the anode and -68 mV/pH for the cathode, coincident with
      thermodynamic estimations. Open circuit voltage reached a maximum (741 mV) at pH
      7, and maximum power density was highest (712 mW/m2) at pH 6.5 as the cathode
      performance improved at lower pH. Maximum current density increased and apparent
      half-saturation potential (E(KA)) decreased with increasing medium pH due to
      improved anode performance. An equivalent circuit model composed of two time
      constant processes accurately fit bioanode impedance data. One of these processes
      was consistently the rate-limiting step for acetate-oxidizing exoelectrogenesis,
      with its pH-varying charge transfer resistance R2 ranging from 2- to 321-fold
      higher than the pH-independent charge transfer resistance R1. The associated
      capacitance C2 was 2-3 orders of magnitude larger than C1. R2 was lowest near
      E(KA) and increased by several orders of magnitude at anode potentials above
      E(KA), while R1 was nearly stable. However, fits deviated slightly at potentials
      above E(KA) due to emerging impedance possibly associated with diffusion and
      excessive potential.

PMID- 21902174
TI  - On the thermodynamic stability of clathrate hydrates V: phase behaviors
      accommodating large guest molecules with new reference states.
AB  - We present a method that brings prediction of phase behaviors of various
      clathrate hydrates with firm statistical mechanical ground adopting a different
      reference state from the usual one. Accommodation of a large guest molecule makes
      the frequencies of the lattice vibrational motions higher, which is one of the
      breakdowns of the assumptions in the original van der Waals and Platteeuw theory.
      The frequency modulations are incorporated in the free energy of cage occupation
      in the present method. Moreover, the reference state, which is originally the
      corresponding empty clathrate structure, is alternated to a state where cages of
      at least one sort are fully occupied. This meets the stability condition of
      clathrate hydrates that most of the cages should be accommodated. Owing to this
      new reference state, the thermodynamic stability is evaluated with reasonable
      accuracy from the free energy of cage occupation especially by a large guest
      molecule without considering its dependence on the cage occupancy. This
      conversion is also beneficial to establish a relation between the chemical
      potential of water and the cage occupancy from grandcanonical Monte Carlo
      simulation. We show a new method indeed works well in predicting the dissociation
      pressures of clathrate hydrates containing isobutane, propane, ethane, Xe, and
      CF(4).

PMID- 21902173
TI  - Multistage nanovectors: from concept to novel imaging contrast agents and
      therapeutics.
AB  - Over the last few decades a great variety of nanotechnology based platforms have
      been synthesized and fabricated to improve the delivery of active compounds to a
      disease site. Nanoparticles currently used in the clinic, and the majority of
      nanotherapeutics/nanodiagnostics under investigation, accommodate single- or
      multiple- functionalities on the same entity. Because many heterogeneous
      biological barriers can prevent therapeutic and imaging agents from reaching
      their intended targets in sufficient concentrations, there is an emerging
      requirement to develop a multimodular nanoassembly, in which different components
      with individual specific functions act in a synergistic manner. The multistage
      nanovectors (MSVs) were introduced in 2008 as the first system of this type. It
      comprises several nanocomponents or "stages", each of which is designed to
      negotiate one or more biological barriers. Stage 1 mesoporous silicon particles
      (S1MPs) were rationally designed and fabricated in a nonspherical geometry to
      enable superior blood margination and to increase cell surface adhesion. The main
      task of S1MPs is to efficiently transport nanoparticles that are loaded into
      their porous structure and to protect them during transport from the
      administration site to the disease lesion. Semiconductor fabrication techniques
      including photolithography and electrochemical etching allow for the exquisite
      control and precise reproducibility of S1MP physical characteristics such as
      geometry and porosity. Furthermore, S1MPs can be chemically modified with
      negatively/positively charged groups, PEG and other polymers, fluorescent probes,
      contrast agents, and biologically active targeting moieties including antibodies,
      peptides, aptamers, and phage. The payload nanoparticles, termed stage 2
      nanoparticles (S2NPs), can be any currently available nanoparticles such as
      liposomes, micelles, inorganic/metallic nanoparticles, dendrimers, and carbon
      structures, within the approximate size range of 5-100 nm in diameter. Depending
      upon the physicochemical features of the S1MP (geometry, porosity, and surface
      modifications), a variety of S2NPs or nanoparticle "cocktails" can be loaded and
      efficiently delivered to the disease site. As demonstrated in the studies
      reviewed here, once the S2NPs are loaded into the S1MPs, a variety of novel
      properties emerge, which enable the design of new and improved imaging contrast
      agents and therapeutics. For example, the loading of the MRI Gd-based contrast
      agents onto hemispherical and discoidal S1MPs significantly increased the
      longitudal relaxivity (r1) to values of up to 50 times larger than those of
      clinically available gadolinium-based agents (~4 mM(-1) s(-1)/Gd(3+) ion).
      Furthermore, administration of a single dose of MSVs loaded with neutral
      nanoliposomes containing small interfering RNA (siRNA) targeted against the EphA2
      oncoprotein enabled sustained EphA2 gene silencing for at least 21 days. As a
      result, the tumor burden was reduced in an orthotopic mouse model of ovarian
      cancer. We envision that the versatility of the MSV platform and its emerging
      properties will enable the creation of personalized solutions with broad clinical
      implications within and beyond the realm of cancer theranostics.

PMID- 21902175
TI  - Bioactive prenylogous cannabinoid from fiber hemp (Cannabis sativa).
AB  - The waxy fraction from the variety Carma of fiber hemp (Cannabis sativa) afforded
      the unusual cannabinoid 4, identified as the farnesyl prenylogue of cannabigerol
      (CBG, 1) on the basis of its spectroscopic properties. A comparative study of the
      profile of 4 and 1 toward metabotropic (CB1, CB2) and ionotropic (TRPV1, TRPV2,
      TRPM8, TRPA1) targets of phytocannabinoids showed that prenylogation increased
      potency toward CB2 by ca. 5-fold, with no substantial difference toward the other
      end-points, except for a decreased affinity for TRPM8. The isolation of 4
      suggests that C. sativa could contain yet-to-be-discovered prenylogous versions
      of medicinally relevant cannabinoids, for which their biological profiles could
      offer interesting opportunities for biomedical exploitation.

PMID- 21902177
TI  - Inducing effect of additive agents on coordination assembly of silver(I) nitrate
      with 3,5-bis(2-pyridyl)-4-amino-1,2,4-triazole: supramolecular isomerism and
      interconversion.
AB  - By using different organic acids as additive agents, hydrothermal reactions of
      AgNO(3) with 3,5-bis(2-pyridyl)-4-amino-1,2,4-triazole (2-bpt) lead to formation
      of two conformational polymorphs of [Ag(2-bpt)](NO(3)) with bimetallocyclic and 1
      D helical coordination patterns. Interconversion between the two supramolecular
      isomers can be achieved under proper conditions, which will pass through the same
      intermediate state.

PMID- 21902176
TI  - Surface eroding, liquid injectable polymers based on 5-ethylene ketal epsilon
      caprolactone.
AB  - Liquid, injectable hydrophobic polymers are potentially useful as depot systems
      for localized drug delivery. Low molecular weight polymers of 5-ethylene ketal
      epsilon-caprolactone and copolymers of this monomer with D,L-lactide were
      prepared and their properties assessed with respect to their suitability for this
      purpose. The polymers were amorphous and of low viscosity, and the viscosity was
      adjustable by choice of initiator and/or by copolymerizing with D,L-lactide.
      Lower viscosity polymers were attained by using 350 Da methoxy poly(ethylene
      glycol) as an initiator in comparison to octan-1-ol, while copolymerization with
      D,L-lactide increased viscosity. The initiator used had no significant effect on
      the rate of mass loss in vitro, and copolymers with D,L-lactide (DLLA) degraded
      faster than 5-ethylene ketal epsilon-caprolactone (EKC) homopolymers. For the EKC
      based polymers, a nearly constant degradation rate was observed. This finding was
      attributed to the hydrolytic susceptibility of the EKC-EKC ester linkage, which
      was comparable to that of DLLA-DLLA, coupled with a higher molecular weight of
      the water-soluble degradation product and the low initial molecular weight of the
      EKC-based polymers. Cytotoxicity of the hydrolyzed EKC monomer to 3T3 fibroblast
      cells was comparable to that of epsilon-caprolactone, suggesting that polymers
      prepared from EKC may be well tolerated upon in vivo implantation.

PMID- 21902178
TI  - Synthesis and properties of metal-ligand complexes with endohedral amine
      functionality.
AB  - A series of tetracationic M(2)L(4) palladium-pyridyl complexes with endohedral
      amine functionality have been synthesized. The complexes were analyzed by NMR
      techniques (including Diffusion NMR and 2D NOESY), electrospray ionization (ESI)
      mass spectrometry, and X-ray crystallography. The solid state analysis shows a
      large change in crystal morphology upon introduction of the endohedral amine
      groups, caused by deleterious interactions between the amines and the triflate
      counterions from the coordination process. Combination of different ligands
      allows analysis of ligand exchange rates via NMR analysis, with half-lives on the
      order of 3 h, independent of the donor properties of the ligand. Self-sorting
      behavior is observed, with more electron-rich ligands being favored. The amine
      containing and extended complexes are strongly fluorescent, giving quantum yields
      of up to 83%.

PMID- 21902179
TI  - Nitrogen atom transfer from iron(IV) nitrido complexes: a dual-nature transition
      state for atom transfer.
AB  - The mechanism of nitrogen atom transfer from four-coordinate tris(carbene)borate
      iron(IV) nitrido complexes to phosphines and phosphites has been investigated. In
      the absence of limiting steric effects, the rate of nitrogen atom transfer to
      phosphines increases with decreasing phosphine sigma-basicity. This trend has
      been quantified by a Hammett study with para-substituted triarylphosphines, and
      is contrary to the expectations of an electrophilic nitrido ligand. On the basis
      of electronic structure calculations, a dual-nature transition state for nitrogen
      atom transfer is proposed, in which a key interaction involves the transfer of
      electron density from the nitrido highest occupied molecular orbital (HOMO) to
      the phosphine lowest unoccupied molecular orbital (LUMO). Compared to analogous
      atom transfer reactions from a 5d metal, these results show how the electronic
      plasticity of a 3d metal results in rapid atom transfer from pseudotetrahedral
      late metal complexes.

PMID- 21902181
TI  - Multimetallic synergic sedation of a labile sodium atrane: synthesis and
      characterization of a tetranuclear sodium atrane cation complex.
AB  - A series of sodium and aluminum atrane complexes of Na(3)L(THF)(5) (1),
      [AlLMe][Na(4)L(THF)(6)] (2), AlL(THF) (3), AlNaLMe(THF)(2) (4), and
      AlNaLOBn(THF)(2) (5), wherein L = tris(2-oxy-4,6-di-tert-butyl-benzyl)amine, were
      synthesized and characterized by NMR, X-ray crystallography, and elemental
      analysis. The trinuclear sodium atrane complex of Na(3)L(THF)(5) (1) is labile at
      room temperature; however, the tetranuclear sodium atrane cation in complex 2 can
      be stabilized by a multimetallic synergetic effect due to a firm interaction ring
      of -[Na-O-benzene](3)-. Complex 2 is also the first example of a sodatrane and
      alumatrane ion-paired complex in which both the cationic and anionic moieties
      contain an atrane ligand.

PMID- 21902182
TI  - Length-controllable catalyzing-synthesis and length-corresponding properties of
      FeCo/Pt nanorods.
AB  - Newly designed magnetic-alloy/noble-metal FeCo/Pt nanorods have been first
      reported and fabricated through a length-controllable catalyzing-synthesis
      process in which the growth of FeCo nanorods was induced on Pt nanotips. The
      length of FeCo/Pt nanorods depends on the number of platinum nanotips. The
      proposed synthesis mechanism was corroborated by scanning electron microscopy,
      transition electron microscopy, X-ray diffraction, energy dispersive X-ray
      spectroscopy, and X-ray photoelectron spectroscopy. With the decrease of Fe
      content in Fe(x)Co(96-x)/Pt(4) nanoalloys from 77 to 15, the morphology changes
      from nanorods with different lengths to nanoparticles. The analysis of the
      magnetic hysteresis loops indicated that the magnetic saturation and coercivity
      were strongly dependent on the length of the nanorods in which maximum saturation
      magnetization and minimum coercivity were obtained for Fe(77)Co(19)/Pt(4)
      nanorods with the length of ~2.5 MUm. In particular, FeCo/Pt exhibited length
      dependent reactivity towards 1,1,2,2-tetrachloroethane, and Fe(77)Co(19)/Pt(4)
      nanorods with the length of ~2.5 MUm yielded the greatest dechlorination rate.
      Moreover, Pt can enhance the dechlorination of 1,1,2,2-tetrachloroethane.

PMID- 21902183
TI  - Modulating magnetic dynamics of three Dy2 complexes through keto-enol tautomerism
      of the o-vanillin picolinoylhydrazone ligand.
AB  - Complexation of dysprosium(III) with the heterodonor chelating ligand o-vanillin
      picolinoylhydrazone (H(2)ovph) in the presence of different bases affords three
      new dinuclear dysprosium(III) coordination compounds, namely,
      [Dy(2)(ovph)(2)(NO(3))(2)(H(2)O)(2)].2H(2)O (1),
      [Dy(2)(Hovph)(ovph)(NO(3))(2)(H(2)O)(4)].NO(3).2CH(3)OH.3H(2)O (2), and
      Na[Dy(2)(Hovph)(2)(MU(2)-OH)(OH)(H(2)O)(5)].3Cl.3H(2)O (3), where the
      aroylhydrazone ligand adopts different coordination modes in respective
      structures depending on the reaction conditions, as revealed by single-crystal X
      ray analyses to be due to their tautomeric maneuver. The magnetic properties of 1
      3 are drastically distinct. Compounds 1 and 2 show single-molecule-magnet
      behavior, while no out-of-phase alternating-current signal is noticed for 3. The
      structural differences induced by the different coordinate fashions of the ligand
      may influence the strength of the local crystal field, the magnetic interactions
      between metal centers, and the local tensor of anisotropy on each Dy site and
      their relative orientations, therefore generating dissimilar dynamic magnetic
      behavior.

PMID- 21902184
TI  - Relipidated tissue factor linked to collagen surfaces potentiates platelet
      adhesion and fibrin formation in a microfluidic model of vessel injury.
AB  - Microfluidic devices allow for the controlled perfusion of human or mouse blood
      over defined prothrombotic surfaces at venous and arterial shear rates. To mimic
      in vivo injuries such a plaque rupture, the need exists to link lipidated tissue
      factor (TF) to surface-bound collagen fibers. Recombinant TF was relipidated in
      liposomes of phosphatidylserine/phosphatidylcholine/biotin-linked
      phosphatidylethanolamine (20:79:1 PS/PC/bPE molar ratio). Collagen was patterned
      in a 250-MUm-wide stripe and labeled with biotinylated anticollagen antibody
      which was then bound with streptavidin, allowing the subsequent capture of the TF
      liposomes. To verify and detect the TF liposome-collagen assembly, individual
      molecular complexes of TF-factor VIIa on collagen were visualized using the
      proximity ligation assay (PLA) to produce discretely localized fluorescent events
      that were strictly dependent on the presence of factor VIIa and primary
      antibodies against TF or factor VIIa. Perfusion for 450 s (wall shear rate, 200
      s(-1)) of corn trypsin inhibitor (CTI, a factor XIIa inhibitor) treated whole
      blood over the stripe of TF-collagen enhanced platelet adhesion by 30 +/- 8% (p <
      0.001) and produced measurable fibrin (>50-fold increase) as compared to surfaces
      lacking TF. PS/PC/bPE liposomes lacking TF resulted in no enhancement of platelet
      deposition. Essentially no fibrin was formed during perfusion over collagen
      surfaces or collagen surfaces with liposomes lacking TF despite the robust
      platelet deposition, indicating a lack of kinetically significant platelet-borne
      tissue factor in healthy donor blood. This study demonstrates a reliable approach
      to link functionally active TF to collagen for microfluidic thrombosis studies.

PMID- 21902185
TI  - Human butyrylcholinesterase-cocaine binding pathway and free energy profiles by
      molecular dynamics and potential of mean force simulations.
AB  - In the present study, we have performed combined molecular dynamics and potential
      of mean force (PMF) simulations to determine the enzyme-substrate (ES) binding
      pathway and the corresponding free energy profiles for wild-type
      butyrylcholinesterase (BChE) binding with (-)/(+)-cocaine and for the A328W/Y332G
      mutant binding with (-)-cocaine. According to the PMF simulations, for each ES
      binding system, the substrate first binds with the enzyme at a peripheral anionic
      site around the entrance of the active-site gorge to form the first ES complex
      (ES1-like) during the binding process. Further evolution from the ES1-like
      complex to the nonprereactive ES complex is nearly barrierless, with a free
      energy barrier lower than 1.0 kcal/mol. So, the nonprereactive ES binding process
      should be very fast. The rate-determining step of the entire ES binding process
      is the subsequent evolution from the nonprereactive ES complex to the prereactive
      ES complex. Further accounting for the entire ES binding process, the PMF-based
      simulations qualitatively reproduced the relative order of the experimentally
      derived binding free energies (DeltaG(bind)), although the simulations
      systematically overestimated the magnitude of the binding affinity and
      systematically underestimated the differences between the DeltaG(bind) values.
      The obtained structural and energetic insights into the entire ES binding process
      provide a valuable base for future rational design of high-activity mutants of
      BChE as candidates for an enzyme therapy for cocaine overdose and abuse.

PMID- 21902186
TI  - Cytotoxic C21 and C22 terpenoid-derived metabolites from the sponge Ircinia sp.
AB  - One novel C21 terpenoidal natural product, ircinolin A (2), two new C22
      furanoterpene metabolites, 15-acetylirciformonin B (3) and 10-acetylirciformonin
      B (4), and two known compounds, irciformonin B (1) and irciformonin F (5), were
      isolated from the sponge Ircinia sp. The structures of these compounds were
      elucidated on the basis of their spectroscopic data. Moreover, the absolute
      configuration of 1 was determined by Mosher's method. Among these metabolites, 2
      is the first C21 terpenoid-derived metabolite to be reported from this genus.
      Compounds 1 and 3-5 exhibited significant cytotoxic activity against K562, DLD-1,
      HepG2, and Hep3B cancer cell lines.

PMID- 21902187
TI  - Carbon nanotube memory by the self-assembly of silicon nanocrystals as charge
      storage nodes.
AB  - A memory structure based on self-aligned silicon nanocrystals (Si NCs) grown over
      Al(2)O(3)-covered parallel-aligned carbon nanotubes (CNTs) by gas source
      molecular beam epitaxy is reported. Electrostatic force microscopy
      characterizations directly prove the charging and discharging of discrete NCs
      through the Al(2)O(3) layer covering the CNTs. A CNT field effect transistor
      based on the NC/CNT structure is fabricated and characterized, demonstrating
      evident memory characteristics. Direct tunneling and Fowler-Nordheim tunneling
      phenomena are observed at different programming/erasing voltages. Retention is
      demonstrated to be on the order of 10(4) s. Although there is still plenty of
      room to enhance the performance, the results suggest that CNT-based NC memory
      with diminutive CNTs and NCs could be an alternative structure to replace
      traditional floating gate memory.

PMID- 21902188
TI  - Tetrylenes chelated by hybrid amido-amino ligand: derivatives of 2-[(N,N
      dimethylamino)methyl]aniline.
AB  - Reaction of 2-[(dimethylamino)methyl]aniline with butyllithium, followed by
      conversion with trimethylsilyl, triphenylsilyl, triphenylgermyl,
      trimethylstannyl, or tri-n-butylstannyl chloride, gives the corresponding
      substituted aniline. These compounds were further deprotonated by butyllithium
      and reacted with germanium, tin, and lead dichlorides, respectively, in both
      stoichiometric ratios 2:1 and 1:1, providing the target homo- ([2
      (Me(2)NCH(2))C(6)H(4)(YR(3))N](2)M) and heteroleptic ([2
      (Me(2)NCH(2))C(6)H(4)(YR(3))N]MCl) germylenes and stannylenes, where M = Ge, Sn,
      Y = Si, Ge, and R = Me, Ph. Unlike all of these cases, the heteroleptic
      plumbylene can only be obtained with this reaction when the amide is substituted
      by a trimethylsilyl moiety. Anilines substituted by trimethyltin or tri-n
      butyltin moieties gave transmetalation products after the second deprotonation by
      butyllithium. The trimethyltin-substituted stannylenes could likewise not be
      obtained by hexamethyldisilazane elimination of (trimethylstannyl)-2
      [(dimethylamino)methyl]aniline with 0.5 mol equiv of either
      bis[bis(trimethylsilyl)amido]tin or {bis[bis(trimethylsilyl)amido]tin chloride}.
      Products of these reactions are heterocubanes with compositions {[2
      (Me(2)NCH(2))C(6)H(4)N]Sn}(4) and [2-(Me(2)NCH(2))C(6)H(4)N](2)(MU(2)
      SnMe(2))(2), respectively, and Me(4)Sn or Me(3)SnCl. The structures of
      trimethylsilyl- and triphenylgermyl-substituted germylenes, stannylenes, and
      plumbylenes, as well as a number of their precursors, in the crystalline state,
      were investigated by X-ray diffraction and NMR spectroscopy in solution. Density
      functional theory methods were used for evaluation of the structures of several
      compounds.

PMID- 21902190
TI  - Intriguing two-dimensional assembly of cobaloxime with a [Zn2(OOCR)4] center.
AB  - We report the synthesis and crystallographic studies of paddlewheel-based methyl
      cobaloxime assembly formed from methyl cobaloxime, isonicotinic acid, and
      Zn(NO(3))(2). The cobaloxime units are assembled over two-dimensional metal
      organic polyhedra constructed from isonicotinate and Zn metal ions.

PMID- 21902189
TI  - VO2+ complexation by bioligands showing keto-enol tautomerism: a potentiometric,
      spectroscopic, and computational study.
AB  - The interaction of VO(2+) ion with ligands of biological interest that are
      present in important metabolic pathways--2-oxopropanoic acid (pyruvic acid,
      pyrH), 3-hydroxy-2-oxopropanoic acid (3-hydroxypyruvic acid, hydpyrH),
      oxobutanedioic acid (oxalacetic acid, oxalH(2)), (S)-hydroxybutanedioic acid (l
      malic acid, malH(2)), and 2,3-dihydroxy-(E)-butanedioic acid (dihydroxyfumaric
      acid, dhfH(2))--was described. Their complexing capability was compared with that
      of similar ligands: 3-hydroxy-2-butanone (hydbut) and 3,4-dihydroxy-3-cyclobutene
      1,2-dione (squaric acid, squarH(2)). All of these ligands (except l-malic acid)
      exhibit keto-enol tautomerism, and the presence of a metal ion can influence such
      an equilibrium. The different systems were studied with electron paramagnetic
      resonance (EPR) and UV-vis spectroscopies and with pH potentiometry. Density
      functional theory (DFT) methods provide valuable information on the relative
      energy of the enol and keto forms of the ligands both in the gas phase and in
      aqueous solution, on the geometry of the complexes, and on EPR and electronic
      absorption parameters. The results show that most of the ligands behave like
      alpha-hydroxycarboxylates, forming mono- and bis-chelated species with (COO(-),
      O(-)) coordination, demonstrating that the metal ion is able to stabilize the
      enolate form of some ligands. With dihydroxyfumaric acid, the formation of a non
      oxidovanadium(IV) complex, because of rearrangement of dihydroxyfumaric to
      dihydroxymaleic acid (dhmH(2)), can be observed. With 3-hydroxy-2-butanone and
      3,4-dihydroxy-3-cyclobutene-1,2-dione, complexation of VO(2+) does not take place
      and the reason for this behavior is explained by chemical considerations and
      computational calculations.

PMID- 21902191
TI  - Thorium(IV) molecular clusters with a hexanuclear Th core.
AB  - Three polynuclear thorium(IV) molecular complexes have been synthesized under
      ambient conditions from reactions of an amorphous Th precipitate, obtained via
      hydrolysis, with carboxylate functionalized ligands. The structures of
      Th(6)(OH)(4)O(4)(H(2)O)(6)(HCO(2))(12).nH(2)O (1),
      Th(6)(OH)(4)O(4)(H(2)O)(6)(CH(3)CO(2))(12).nH(2)O (2),
      Th(6)(OH)(4)O(4)(H(2)O)(6)(ClCH(2)CO(2))(12).4H(2)O (3) each consist of a
      hexanuclear Th core wherein six 9-coordinate Th(IV) cations are bridged by four
      MU(3)-hydroxo and four MU(3)-oxo groups. Each Th(IV) center is additionally
      coordinated to one bound "apical" water molecule and four oxygen atoms from
      bridging carboxylate functionalized organic acid units. "Decoration" of the
      cationic [Th(6)(MU(3)-O)(4)(MU(3)-OH)(4)](12+) cores by anionic shells of R-COO(
      ) ligands (R = H, CH(3), or CH(2)Cl) terminates the oligomers and results in the
      formation of discrete, neutral molecular clusters. Electronic structure
      calculations at the density functional theory level predicted that the most
      energetically favorable positions for the protons on the hexanuclear core result
      in the cluster with the highest symmetry with the protons separated as much as
      possible. The synthesis, structure, and characterization of the materials are
      reported.

PMID- 21902192
TI  - Different effects of a cotemplate and [(transition-metal)(1,10
      phenanthroline)(m)]2+ (m = 1-3) complex cations on the self-assembly of a series
      of hybrid selenidostannates showing combined optical properties of organic and
      inorganic components.
AB  - 1,10-Phenanthroline (phen) and monoprotonated methylamine molecules were used as
      a novel cotemplate to direct the formation of a new inorganic-organic hybrid
      selenidostannate, (CH(3)NH(3))(4)(Sn(2)Se(6)).6phen (1); while the utilization of
      three types of transition-metal (TM) phen complex cations with the TM/phen ration
      of 1:1, 1:2, and 1:3 as structure directors affords {[Mn(phen)(2)](2)(MU(2)
      Sn(2)Se(6))}.H(2)O (2a), {[Fe(phen)(2)](2)(MU(2)-Sn(2)Se(6))} (2b),
      {[Mn(phen)](2)(MU(4)-Sn(2)Se(6))}(n) (3), {[Mn(phen)(2)](Sn(2)Se(5))}(n) (4), and
      [Fe(phen)(3)](n)(Sn(3)Se(7))(n).1.25nH(2)O (5). These compounds show diverse
      structures with the selenidostannate anions varying from discrete, MU(2)- and
      MU(4)- (Sn(2)Se(6))(4-) anions, to one-dimensional (1-D)
      (1)(infinity)(Sn(2)Se(5)(2-)) anionic chains, and two-dimensional (2-D) extended
      (2)(infinity)(Sn(3)Se(7)(2-)) anionic layers, demonstrating different structure
      directing abilities of the cotemplate and the three types of TM phen complex
      cations. This work clearly indicates that the approach of modifying the number of
      the free coordination sites of unsaturated TM phen complex cations is very
      exciting as a way to synthesize novel hybrid chalcogenidometalates. Of particular
      interest, the present compounds exhibit interesting optical properties that
      reflect the combined effects of both photoluminescence-active organic components
      and semiconducting inorganic chalcogenidometalate anionic networks.

PMID- 21902193
TI  - Kinetics and thermodynamics of limonene ozonolysis.
AB  - Using density functional methods, the initial reaction steps of limonene
      ozonolysis have been investigated with a focus on primary ozonide formation and
      its decomposition to Criegee intermediates and carbonyl compounds. The ozonide
      formation is highly exothermic, and the decomposition channels have similar free
      energies of activation, DeltaG(?), indicating that there is no primary pathway
      for ozonide decomposition. Assuming that ozonide formation is the rate limiting
      step, the theoretical rate coefficient, k = 1.6 * 10(-16) molecule(-1) cm(3) s(
      1), evaluated at the CCSD(T)/6-31G(d,p)//BHandHLYP/cc-pvdz level and 298.15 K for
      d-limonene is in good agreement with the experimental value, k(exp) = 3.3 * 10(
      16) molecule(-1) cm(3) s(-1). The theoretical Arrhenius expression is also in
      good agreement with experimental results.

PMID- 21902194
TI  - Plasmon-driven selective deposition of au bipyramidal nanoparticles.
AB  - We demonstrate the plasmon-selective and driven deposition of (bipyramidal) Au
      nanoparticles on transparent substrates (glass coverslips) utilizing total
      internal reflection (TIR) illumination. Near-IR laser light undergoing TIR at a
      glass-water interface causes colloidal Au bipyramids to irreversibly deposit onto
      the glass surface. We demonstrate that the deposition process has particle (i.e.,
      shape) selectivity that is associated with resonant plasmon excitation.
      Specifically, the deposition is selective for the bipyramids over spheroidal
      particles that are also present in solution due to the former's surface plasmon
      resonance in the near-IR region. Our measurements, finite difference time domain
      simulations, and the results of an analytical model show that the optical (i.e.,
      scattering and gradient) forces that act on the particles are large and cause the
      observed acceleration and directed motion of the bipyramids. These directional
      forces play a major role in the spatial pattern of particle deposition that is
      observed. In addition, the resonant photothermal heating of the Au bipyramids
      causes an irreversible loss in colloidal stability, thus allowing them to adhere
      to the surface. Structural (i.e., scanning electron microscopy) characterization
      of the deposited bipyramids reveals a slight reduction in aspect ratio relative
      to the ensemble, consistent with the proposed (heating) mechanism. To our
      knowledge this is the first demonstration of the plasmon-selective deposition of
      metal nanoparticles from a heterogeneous mixture.

PMID- 21902195
TI  - Structural relationships of stemona alkaloids: assessment of species-specific
      accumulation trends for exploiting their biological activities.
AB  - On the basis of a comparison of 42 Stemona samples, representing eight different
      species collected and cultivated in Thailand, species-specific accumulation
      trends of Stemona alkaloids were analyzed. An overview was achieved by
      comparative HPLC analyses of methanolic crude extracts of underground parts
      coupled with diode array or evaporative light scattering detectors. All major
      compounds were isolated and their structures elucidated by NMR and MS analyses.
      Protostemonine- and stichoneurine-type derivatives dominated, from which the
      latter characterize S. tuberosa and S. phyllantha accumulating species-specific
      isomers of tuberostemonine (3). The widespread S. curtisii and S. collinsiae
      clearly deviate by protostemonine-type derivatives dominated by stemofoline (10)
      and/or didehydrostemofoline (11). Further diversification within this structural
      type results from a mutual accumulation of derivatives with a pyrrolo- or
      pyridoazepine nucleus, leading to chemical variability in S. curtisii and S.
      aphylla.

PMID- 21902196
TI  - Global survey of the bovine salivary proteome: integrating multidimensional
      prefractionation, targeted, and glycocapture strategies.
AB  - Saliva is easily obtainable from a large number of animals in a noninvasive
      manner and contains a wide diversity of compounds including hormones,
      metabolites, and proteins that may be a good source of biomarkers of health and
      disease. Here we have used a combination of multidimensional prefractionation,
      targeted, and glycocapture methodologies to profile the bovine salivary proteome.
      The nontargeted approach used four different separation methodologies consisting
      of SDS-PAGE, Off-gel fractionation, RP-HPLC, and SCX-HPLC. In the targeted
      approach, we've employed a hypothesis-based methodology by only selecting
      extracellular proteins from in silico data. Finally, the hydrazide capture
      methodology not only enabled us to identify formerly N-linked glycoproteins but
      it also provided a selective enrichment process for the identification of low
      abundance proteins. Together, the three different approaches identified 402
      salivary proteins and 45 N-linked glycoproteins. A large number of these proteins
      have previously been uncharacterized in bovine saliva. To date, this is the
      largest global survey of the bovine salivary proteome and expands the potential
      of the diagnostic utility of this fluid to guide development of experiments
      seeking biomarkers for health traits (i.e., disease resistance) as well as feed
      conversion efficiency and productivity traits in dairy and beef cattle.

PMID- 21902197
TI  - Regioselective synthesis of 5-monostyryl and 2-tetracyanobutadiene BODIPY dyes.
AB  - Several unsymmetrically 2,5-disubstituted BODIPY dyes were obtained from 2
      substituted derivatives (iodo, ethynylaryl) using a regioselective Knoevenagel
      condensation reaction with dimethylaminobenzaldehyde. The unsaturated,
      unsymmetrical 2-ethynyl-5-styryl-BODIPY undergoes a regioselective [2 + 2]
      cycloaddition reaction with tetracyanoethylene leading to the 1,1,4,4
      tetracyanobuta-1,3-diene (TCBD) derivative. This shows rich redox activity with
      two reversible oxidation and three reversible reduction waves at +0.72 V, +1.04
      V; -0.32 V, -0.78 V, and -1.50 V, respectively.

PMID- 21902198
TI  - Organocatalytic asymmetric intermolecular dehydrogenative alpha-alkylation of
      aldehydes using molecular oxygen as oxidant.
AB  - An organocatalytic enantioselective intermolecular oxidative dehydrogenative
      alpha-alkylation of aldehydes via benzylic C-H bond activation has been
      developed. The asymmetric reaction is smoothly fulfilled by using simple and
      green molecular oxygen as the oxidant. Two hydrogen dissociations make this
      transformation more environmentally benign because of high atom efficiency.

PMID- 21902199
TI  - Organocatalytic asymmetric aldol reaction of hydroxyacetone with beta,gamma
      unsaturated alpha-keto esters: facile access to chiral tertiary alcohols.
AB  - An efficient direct asymmetric aldol reaction between hydroxyacetone and
      beta,gamma-unsaturated alpha-keto esters has been successfully developed. In the
      presence of 9-amino-9-deoxy-epi-cinchonine and trifluoroacetic acid, the direct
      aldol reaction of O-protected hydroxyacetone proceeded in a highly
      enantioselective manner, affording the desired adducts containing a chiral
      tertiary alcohol in high yields and with excellent enantioselectivities. The
      aldol products obtained are valuable precursors for the synthesis of 2
      substituted glycerol derivatives.

PMID- 21902200
TI  - Total synthesis of pacidamycin D by Cu(I)-catalyzed oxy enamide formation.
AB  - The first total synthesis of pacidamycin D, which is expected to be a good
      candidate as an antibacterial agent against P. aeruginosa, is described. The key
      elements of our approach feature an efficient and stereocontrolled construction
      of the Z-oxyvinyl iodide and copper-catalyzed cross-coupling with the
      tetrapeptide carboxamide.

PMID- 21902201
TI  - Tandem thiol switch synthesis of peptide thioesters via N-S acyl shift on
      thiazolidine.
AB  - An efficient "thiol switch" approach for the synthesis of peptide thioesters via
      an acid-catalyzed N-S acyl shift and a thioester exchange reaction in tandem with
      concurrent removal of protecting groups is described. This method employs novel 2
      (thiomethyl)thiazolidine (TMT)-anchored resins and is fully compatible with Fmoc
      chemistry.

PMID- 21902202
TI  - In-use measurement of activity, energy use, and emissions of a plug-in hybrid
      electric vehicle.
AB  - Plug-in hybrid electric vehicles (PHEVs) could reduce transportation air
      emissions and energy use. However, a method is needed for estimating on-road
      emissions of PHEVs. To develop a framework for quantifying microscale energy use
      and emissions (EU&E), measurements were conducted on a Toyota Prius retrofitted
      with a plug-in battery system on eight routes. Measurements were made using the
      following: (1) a data logger for the hybrid control system; (2) a portable
      emissions measurement system; and (3) a global positioning system with barometric
      altimeter. Trends in EU&E are estimated based on vehicle specific power. Energy
      economy is quantified based on gasoline consumed by the engine and grid energy
      consumed by the plug-in battery. Emissions from electricity consumption are
      estimated based on the power generation mix. Fuel use is approximately 30% lower
      during plug-in battery use. Grid emissions were higher for CO2, NO(x), SO2, and
      PM compared to tailpipe emissions but lower for CO and hydrocarbons. EU&E depends
      on engine and plug-in battery operation. The use of two energy sources must be
      addressed in characterizing fuel economy; overall energy economy is 11% lower if
      including grid energy use than accounting only for fuel consumption.

PMID- 21902203
TI  - Nature of electronic states in atomically thin MoS2 field-effect transistors.
AB  - We present low-temperature electrical transport experiments in five field-effect
      transistor devices consisting of monolayer, bilayer, and trilayer MoS(2) films,
      mechanically exfoliated onto Si/SiO(2) substrate. Our experiments reveal that the
      electronic states in all films are localized well up to room temperature over the
      experimentally accessible range of gate voltage. This manifests in two
      dimensional (2D) variable range hopping (VRH) at high temperatures, while below
      ~30 K, the conductivity displays oscillatory structures in gate voltage arising
      from resonant tunneling at the localized sites. From the correlation energy
      (T(0)) of VRH and gate voltage dependence of conductivity, we suggest that
      Coulomb potential from trapped charges in the substrate is the dominant source of
      disorder in MoS(2) field-effect devices, which leads to carrier localization, as
      well.

PMID- 21902204
TI  - Effects of a catalytic volatile particle remover (VPR) on the particulate matter
      emissions from a direct injection spark ignition engine.
AB  - Emissions of fine particles have been shown to have a large impact on the
      atmospheric environment and human health. Researchers have shown that gasoline
      engines, especially direct injection spark ignition (DISI) engines, tend to emit
      large amounts of small size particles compared to diesel engines fitted with
      diesel particulate filters (DPFs). As a result, the particle number emissions of
      DISI engines will be restricted by the forthcoming EU6 legislation. The
      particulate emission level of DISI engines means that they could face some
      challenges in meeting the EU6 requirement. This paper is an experimental study on
      the size-resolved particle number emissions from a spray guided DISI engine and
      the performance of a catalytic volatile particle remover (VPR), as the EU
      legislation seeks to exclude volatile particles. The performance of the catalytic
      VPR was evaluated by varying its temperature and the exhaust residence time. The
      effect of the catalytic VPR acting as an oxidation catalyst on particle emissions
      was also tested. The results show that the catalytic VPR led to a marked
      reduction in the number of particles, especially the smaller size (nucleation
      mode) particles. The catalytic VPR is essentially an oxidation catalyst, and when
      post three-way catalyst (TWC) exhaust was introduced to the catalytic VPR, the
      performance of the catalytic VPR was not affected much by the use of additional
      air, i.e., no significant oxidation of the PM was observed.

PMID- 21902205
TI  - Metabolic signature of pregnant women with neural tube defects in offspring.
AB  - Neural tube defects (NTDs) are one of the most common types of birth defects,
      affecting approximately 1 of every 1000 pregnancies in the United States and an
      estimated 300 000 newborns worldwide each year. The metabolic signature of
      pregnant women with NTDs in offspring has not previously been characterized. In
      this paper, we report a profiling study that characterized the serum metabolome
      of 101 pregnant women affected with NTDs in offspring in comparison with 143
      pregnant women with normal pregnancy outcomes in Lvliang prefecture, the area
      with the highest birth prevalence of NTDs in China. A serum metabonomic study was
      also conducted to identify significantly altered metabolites associated with di-n
      butyl phthalate (DBP)-induced teratogenesis in mice. The metabolic signature of
      NTD in pregnant women is characterized by the impaired mitochondrial respiration,
      neurotransmitter gamma-aminobutyric acid, and methionine cycle. Of interest,
      consistent findings from DBP-induced teratogenesis in mice demonstrated increased
      succinate and decreased fumarate, suggesting an inhibited succinic dehydrogenase
      implicated in the defective mitochondria. The characteristic disruption of
      maternal metabolism offers important insights into metabolic mechanisms
      underlying human NTDs as well as potential preventive strategies.

PMID- 21902206
TI  - Synthesis of benzothiophene derivatives by Pd-catalyzed or radical-promoted
      heterocyclodehydration of 1-(2-mercaptophenyl)-2-yn-1-ols.
AB  - Novel and convenient approaches to benzothiophene derivatives 3 and 5 have been
      developed, based on heterocyclization reactions of 1-(2-mercaptophenyl)-2-yn-1
      ols 2 or 4, respectively, readily available from alkynylation of 2
      mercaptobenzaldehydes or 1-(2-mercaptophenyl) ketones 1. In particular, 1-(2
      mercaptophenyl)-2-yn-1-ols 2, bearing a CH(2)R substituent on the triple bond (R
      = alkyl, aryl), were conveniently converted in fair to good yields (55-82%) into
      (E)-2-(1-alkenyl)benzothiophenes 3 when allowed to react in the presence of
      catalytic amounts (2 mol %) of PdI(2) in conjunction with KI (KI:PdI(2) molar
      ratio =10) at 80-100  degrees C in MeCN as the solvent, through a
      heterocyclodehydration process. On the other hand, 2-alkoxymethylbenzothiophenes
      5 were selectively obtained in fair to excellent yields (49-98%) via a radical
      promoted substitutive heterocyclodehydration process, by reacting 1-(2
      mercaptophenyl)-2-yn-1-ols 4 (bearing an alkyl or aryl substituent on the triple
      bond) in alcoholic media at 80-100  degrees C in the presence of a radical
      initiator, such as AIBN.

PMID- 21902207
TI  - Polarization closure in PbZr((0.42))Ti((0.58))O(3) nanodots.
AB  - Domain states in PbZr((0.42))Ti((0.58))O(3) single-crystal ferroelectric
      nanodots, formed on cooling through the Curie temperature, were imaged by
      transmission electron microscopy. In the majority of cases, 90 degrees  stripe
      domains were found to form into four distinct "bundles" or quadrants. Detailed
      analysis of the dipole orientations in the system was undertaken, using both dark
      field imaging and an assumption that charged domain walls were energetically
      unfavorable in comparison to uncharged walls. On this basis, we conclude that the
      dipoles in these nanodots are arranged such that the resultant polarizations,
      associated with the four quadrant domain bundles, form into a closed loop. This
      "polarization closure" pattern is reminiscent of the flux-closure already
      commonly observed in soft ferromagnetic microdots but to date unseen in analogous
      ferroelectric dots.

PMID- 21902208
TI  - Highly enantioselective gamma-amination of alpha,beta-unsaturated acyl chlorides
      with azodicarboxylates: efficient synthesis of chiral gamma-amino acid
      derivatives.
AB  - The cinchona alkaloid-catalyzed gamma-amination of alpha,beta-unsaturated acyl
      chlorides with azodicarboxylates to give the corresponding dihydropyridazinones
      in good yields with high enantioselectivities has been developed. Reductive ring
      opening of the dihydropyridazinones afforded series of cyclic and acyclic gamma
      amino acid derivatives in good yields with high enantiopurity.

PMID- 21902209
TI  - Self assembled liquid crystal polymers on photo-irradiated alignment surfaces for
      tailoring response properties of liquid crystal molecules.
AB  - A liquid crystal polymer (LCP) self-assembled on a photoirradiated substrate can
      modify the viscoelastic response of liquid crystal medium on the substrate. Sum
      frequency vibrational spectroscopy shows that the phenyl groups of LCP are
      oriented epitaxially with layer thickness and an in-plane alignment order much
      higher than that at the photoirradiated surface can be yielded. The liquid
      crystal molecules confined between the LCP-coated substrates reveals a stronger
      correlation among the thermally excited fluctuation modes. Our finding can be
      used to tailor the boundary forces on alignment substrates and to optimize the
      device performance.

PMID- 21902210
TI  - Formation process and solvent-dependent structure of a polyproline self-assembled
      monolayer on a gold surface.
AB  - The formation process and structure of a self-assembled monolayer (SAM) of lipoic
      acid-terminated polyproline on a gold surface in aqueous solution were
      investigated by several techniques. The amount of polyproline molecules on the
      gold surface was determined from the area of the reductive desorption peak, and
      orientation and thickness of the polyproline SAM were determined in situ by
      attenuated total reflection infrared (ATR-IR) spectroscopy and ellipsometry. The
      kinetics of the polyproline SAM formation process were discussed on the basis of
      these results. The in situ IR study confirmed that the conformation of the
      polyproline SAM was changed by changing the solvent from water to methanol and
      methanol to water, as is the case for polyproline dissolved in solution.

PMID- 21902211
TI  - Self-assembled nanotubes and helical tapes from diacetylene nonionic amphiphiles.
      Structural studies before and after polymerization.
AB  - We synthesized new amphiphiles comprised of a single diacetylenic chain and an
      oligoethylenoxide polar chain linked by an amide bond. In aqueous medium, they
      are not soluble at room temperature but form weak gels. Electron microscopy
      studies have shown that they self-assemble into helical tapes or nanotubes with
      lengths of several micrometers, and inner and outer diameters of 50 +/- 1 and 59
      +/- 1 nm, respectively. The wall has a thickness of 10 +/- 1 nm for both kinds of
      objects and has an amphiphile bilayer structure. The hydrophobic chains are
      ordered, and the amide groups are linked with each other by H-bonds. The
      dissociation of the tubes is a first-order transition with an enthalpy of ca. 40
      kJ mol(-1). The nanotubes were photopolymerized to yield purple solutions
      consisting of helical tapes and almost flat ribbons. The polymers exhibit
      irreversible thermochromism upon heating.

PMID- 21902212
TI  - Heterogeneous catalytic hydrogenation of unprotected indoles in water: a green
      solution to a long-standing challenge.
AB  - An environmentally benign procedure for the hydrogenation of unprotected indoles
      is described. The hydrogenation reaction is catalyzed by Pt/C and activated by p
      toluenesulfonic acid in water as a solvent. The efficacy of the method is
      illustrated by the hydrogenation of a variety of substituted indoles to their
      corresponding indolines which were obtained in excellent yields.

PMID- 21902213
TI  - Hydrogen tunneling steps in cyclooxygenase-2 catalysis.
AB  - Cyclooxygenases-1 and -2 are tyrosyl radical (Y.)-utilizing hemoproteins
      responsible for the biosynthesis of lipid-derived autocoids. COX-2, in
      particular, is a primary mediator of inflammation and believed to be up-regulated
      in many forms of cancer. Described here are first-of-a-kind studies of COX-2
      catalyzed oxidation of the substrate analogue linoleic acid. Very large (>=20)
      temperature-independent deuterium kinetic isotope effects (KIEs) on the rate
      constant for enzyme turnover were observed, due to hydrogen atom abstraction from
      the bisallylic C-H(D) of the fatty acid. The magnitude of the KIE depends on the
      O(2) concentration, consistent with reversible H/D tunneling mediated by the
      catalytic Y.. At physiological levels of O(2), retention of the hydrogen
      initially abstracted by the catalytic tyrosine results in strongly temperature
      dependent KIEs on O-H(D) homolysis, also characteristic of nuclear tunneling.

PMID- 21902214
TI  - Evaluation of a medium-polarity ionic liquid stationary phase in the analysis of
      flavor and fragrance compounds.
AB  - The present research is focused on the evaluation, in terms of efficiency and
      polarity, of a recently introduced gas chromatography (GC) column, coated with a
      1,12-di(tripropylphosphonium) dodecane bis(trifluoromethansulfonyl) amide ionic
      liquid stationary phase (SLB-IL59) and its application to the analysis of a
      complex essential oil. The ionic liquid column demonstrated very good efficiency,
      in terms of plate number, and a polarity close to that of the 100%
      poly(ethyleneglycol) stationary phase. In this preliminary evaluation, the SLB
      IL59 30 m column was subjected to bleeding measurements, by means of conventional
      gas chromatography/mass spectrometry (GC/MS) and, in addition, of comprehensive
      2D GC. The SLB-IL59 column (30 m * 0.20 MUm d(f), 0.25 mm i.d.) was then
      evaluated in the analysis of typical essential oil constituents, in the form of
      pure standard compounds. Resolution toward several analytes was measured and the
      results were compared to those obtained with both apolar [silphenylene polymer,
      equivalent to poly(5% diphenyl/95% dimethylsiloxane)] and medium-polarity [100%
      poly(ethyleneglycol)] stationary phases, namely, the most common columns employed
      in the analysis of essential oils; peak symmetry, for different essential oil
      constituents, was also measured and expressed through tailing factors (at 10% of
      peak height). The final part of the investigation was devoted to the GC/MS
      analysis of lemon essential oil, with GC-flame ionization detection (FID) used
      for quantification. Linear retention indices of all the identified compounds were
      determined, and the data obtained were compared to those attained on the apolar
      and "wax" columns. The results obtained in the present investigation reveal the
      great potential of this novel stationary phase, as a medium-polarity alternative,
      in the analysis of essential oils.

PMID- 21902215
TI  - Low-energy electron-induced damage in a trinucleotide containing 5-bromouracil.
AB  - The reaction of low-energy electrons (LEEs; 10 eV) with 5'-TpXpT-3' (TXT), where
      X is uracil (U), thymine (T), and 5-bromouracil (5BrU), was examined by HPLC-UV
      analysis. The presence of 5BrU increased total damage by >50%. The radiation
      products of T5BrUT included TUT (40%), free U, T, 5BrU (23%), and fragments
      (13%). These products may be explained by initial capture of LEEs by the
      nucleobase to form a transient anion, followed by transfer of the electron within
      the molecule and cleavage of susceptible bonds by dissociative electron
      attachment (C-Br, C-N, or C-O bonds). In addition, these products may arise from
      the uracilyl-5-yl (U-5-yl) radicals that undergo H-atom abstraction from the
      sugar moiety. Interestingly, several products contained two sites of cleavage (U,
      pUT, and TUp). The formation of these products was linear with dose, and thus,
      they arise from the single-electron reactions. To explain these products, we
      propose that the reaction of LEEs (10 eV) involves the coupling of two
      dissociative processes in the same molecule (for example, dissociative excitation
      and dissociative electron attachment). The latter reactions may contribute to the
      formation of clustered damage, which is the most deleterious damage induced by
      ionizing radiation.

PMID- 21902216
TI  - Sensitivity of polar and temperate marine organisms to oil components.
AB  - Potential contamination of polar regions due to increasing oil exploitation and
      transportation poses risks to marine species. Risk assessments for polar marine
      species or ecosystems are mostly based on toxicity data obtained for temperate
      species. Yet, it is unclear whether toxicity data of temperate organisms are
      representative for polar species and ecosystems. The present study compared
      sensitivities of polar and temperate marine species to crude oil, 2-methyl
      naphthalene, and naphthalene. Species sensitivity distributions (SSDs) were
      constructed for polar and temperate species based on acute toxicity data from
      scientific literature, reports, and databases. Overall, there was a maximum
      factor of 3 difference in sensitivity to oil and oil components, based on the
      means of the toxicity data and the hazardous concentrations for 5 and 50% of the
      species (HC5 and HC50) as derived from the SSDs. Except for chordates and
      naphthalene, polar and temperate species sensitivities did not differ
      significantly. The results are interpreted in the light of physiological
      characteristics, such as metabolism, lipid fraction, lipid composition,
      antioxidant levels, and resistance to freezing, that have been suggested to
      influence the susceptibility of marine species to oil. As a consequence, acute
      toxicity data obtained for temperate organisms may serve to obtain a first
      indication of risks in polar regions.

PMID- 21902217
TI  - Computational design of a collagen A:B:C-type heterotrimer.
AB  - We have successfully designed an A:B:C collagen peptide heterotrimer using an
      automated computational approach. The algorithm maximizes the energy gap between
      the target and competing misfolded states while enforcing a minimum target
      stability. Circular dichroism (CD) measurements confirm that all three peptides
      are required to form a stable, structured triple helix. This study highlights the
      power of automated computational design, providing model systems to probe the
      biophysics of collagen assembly and developing general methods for the design of
      fibrous proteins.

PMID- 21902218
TI  - Pseudopolyrotaxanes on inorganic nanoplatelets and their supramolecular
      hydrogels.
AB  - In this paper, we demonstrate the first hybrid suprastructure of
      pseudopolyrotaxanes (PPRs) on clay nanoplatelets. Simple end-modification of
      poly(ethylene glycol) with pyridinium (PEG-N(+)) enabled the chains to form
      brushlike conformation on clay surfaces. Thus, the PEG chains were able to thread
      into the cavities of alpha-cyclodextrins (alpha-CDs), leading to hybrid PPR
      hydrogels. This was very different from the unmodified PEG chains, which were
      absorbed onto the clay surface and thus made the PPR formation impossible. The
      hydrogels made of this PPR-on-clay structure displayed a dynamic modulus 1 order
      of magnitude higher than those of the native PPR hydrogels. Furthermore, based on
      the competitive host-guest interactions, such hybrid hydrogels showed fully
      photoreversible sol-gel transition after a competitive guest containing
      azobenzene moiety was introduced.

PMID- 21902219
TI  - In situ electrochemical lithiation/delithiation observation of individual
      amorphous Si nanorods.
AB  - In situ electrochemical lithiation and delithiation processes inside a
      nanobattery consisting of an individual amorphous Si nanorod and ionic liquid
      were explored. Direct formation of the crystalline Li(22)Si(5) phase due to the
      intercalation of Li ions was observed. In addition, the role of the electrolyte
      nanorod interface was examined. It was observed that the lithiation of Si
      nanorods is dominated by surface diffusion. Upon the delithiation process,
      partial decomposition of Li(22)Si(5) particles was observed which can explain the
      irreversible capacity loss that is generally seen in Si anodes. This study shows
      that the radial straining due to lithiation does not cause cracking in nanorods
      as small in diameter as 26 nm, whereas cracks were observed during the lithiation
      of 55 nm Si nanorods.

PMID- 21902221
TI  - Regulation of postprandial blood metabolic variables by TEMPO-oxidized cellulose
      nanofibers.
AB  - Wood cellulose was converted to individual nanofibers of approximately 4 nm width
      and 380-570 nm average length by TEMPO-mediated oxidation. The TEMPO-oxidized
      cellulose nanofibers (TOCNs) were orally administered with glucose and glyceryl
      trioleate to mice and postprandial responses of blood glucose, insulin, glucose
      dependent insulinotropic polypeptide (GIP), and triglycerides were studied. Both
      blood insulin and GIP concentrations were decreased by TOCN with a carboxyl
      content and aspect ratio of 1.2 mmol g(-1) and 120, respectively, in dose
      dependent manners (0-0.3 mg g(-1) body weight). Of the TOCNs examined, that with
      a carboxyl content and aspect ratio of 1.2 mmol g(-1) and 120, respectively, was
      the most effective in reducing postprandial blood glucose, plasma insulin, GIP,
      and triglyceride concentrations. Thus, TOCNs were found to exhibit characteristic
      biological activities when administered to mice and may have potential
      applications in biomedical fields for human health.

PMID- 21902222
TI  - Electroosmotic flow in microchannels with nanostructures.
AB  - Here we report that nanopillar array structures have an intrinsic ability to
      suppress electroosmotic flow (EOF). Currently using glass chips for
      electrophoresis requires laborious surface coating to control EOF, which works as
      a counterflow to the electrophoresis mobility of negatively charged samples such
      as DNA and sodium dodecyl sulfate (SDS) denatured proteins. Due to the intrinsic
      ability of the nanopillar array to suppress the EOF, we carried out
      electrophoresis of SDS-protein complexes in nanopillar chips without adding any
      reagent to suppress protein adsorption and the EOF. We also show that the EOF
      profile inside a nanopillar region was deformed to an inverse parabolic flow. We
      used a combination of EOF measurements and fluorescence observations to compare
      EOF in microchannel, nanochannel, and nanopillar array chips. Our results of EOF
      measurements in micro- and nanochannel chips were in complete agreement with the
      conventional equation of the EOF mobility (MU(EOF-channel) = alphaC(i)(-0.5),
      where C(i) is the bulk concentration of the i-ions and alpha differs in micro-
      and nanochannels), whereas EOF in the nanopillar chips did not follow this
      equation. Therefore we developed a new modified form of the conventional EOF
      equation, MU(EOF-nanopillar) ~ beta[C(i) - (C(i)(2)/N(i))], where N(i) is the
      number of sites available to i-ions and beta differs for each nanopillar chip
      because of different spacings or patterns, etc. The modified equation of the EOF
      mobility that we proposed here was in good agreement with our experimental
      results. In this equation, we showed that the charge density of the nanopillar
      region, that is, the total number of nanopillars inside the microchannel,
      affected the suppression of EOF, and the arrangement of nanopillars into a tilted
      or square array had no effect on it.

PMID- 21902220
TI  - A critical assessment of combined ligand- and structure-based approaches to HERG
      channel blocker modeling.
AB  - Blockade of human ether-a-go-go related gene (hERG) channel prolongs the duration
      of the cardiac action potential and is a common reason for drug failure in
      preclinical safety trials. Therefore, it is of great importance to develop robust
      in silico tools to predict potential hERG blockers in the early stages of drug
      discovery and development. Herein we described comprehensive approaches to assess
      the discrimination of hERG-active and -inactive compounds by combining
      quantitative structure-activity relationship (QSAR) modeling, pharmacophore
      analysis, and molecular docking. Our consensus models demonstrated high
      predictive capacity and improved enrichment and could correctly classify 91.8% of
      147 hERG blockers from 351 inactives. To further enhance our modeling effort,
      hERG homology models were constructed, and molecular docking studies were
      conducted, resulting in high correlations (R2 = 0.81) between predicted and
      experimental pIC50s. We expect our unique models can be applied to efficient
      screening for hERG blockades, and our extensive understanding of the hERG
      inhibitor interactions will facilitate the rational design of drugs devoid of
      hERG channel activity and hence with reduced cardiac toxicities.

PMID- 21902223
TI  - Assessing the severity of rainfall-derived infiltration and inflow and sewer
      deterioration based on the flux stability of sewage markers.
AB  - This study investigated the flux stability of select chemical and biological
      sewage markers, including caffeine, total nitrogen (TN), total suspended solids
      (TSS), E. coli, and enterococci, and their suitability in assessing the severity
      of rainfall-derived infiltration and inflow (RDII) in a residential sewershed. To
      quantify and compare marker flux stability, concentrations of the candidate
      markers in two dry-weather periods were determined and the one-day lag
      autocorrelation coefficients (r) of their mass fluxes were calculated. TN (r =
      0.82-0.88) exhibited higher and more consistent flux stability than TSS (r = 0.49
      0.82), caffeine (r = 0.56-0.58), E. coli (r = 0.36-0.87), and enterococci (by
      culture; r = 0.40-0.52), all of which except enterococci by qPCR (r = -0.10-0.21)
      showed significant autocorrelation. Sewage flows and marker concentrations were
      also monitored in two wet-weather periods, and the severity of RDII (R(RDII))
      were calculated using either flow measurements or marker concentrations
      independently. Corresponding to its outstanding flux stability, R(RDII) values
      estimated by TN predicted all severe RDII instances and gave the highest and most
      consistent correlation (r = 0.74-0.78) among the different sewage markers.
      Overall, the study illustrated the feasibility of using the flux stability of
      sewage markers in assessing the severity of RDII and thereby deterioration levels
      in sewer systems.

PMID- 21902224
TI  - Dietary n-3 polyunsaturated fatty acids and the paradox of their health benefits
      and potential harmful effects.
AB  - There is some evidence to support the toxicity of polyunsaturated fatty acids
      (PUFAs) and their oxidative products, suggesting their involvement in the
      pathogenesis of different chronic diseases, including cancer. It has been shown
      that products of PUFA oxidation may exert a carcinogenic action by forming
      mutagenic adducts with DNA. However, a large amount of evidence accumulated over
      several decades has indicated the beneficial effects of administration of n-3
      PUFAs in the prevention and therapy of a series of diseases. In particular, there
      is much evidence that n-3 PUFAs exert anti-inflammatory and antineoplastic
      effects, whereas n-6 PUFAs promote inflammation and carcinogenesis. In our
      tissues, both of the two classes of PUFAs can be converted into bioactive
      products, incorporated into membrane phospholipids or bound to membrane
      receptors, where they may alter, often in opposite ways, transduction pathways
      and affect important biological processes, such as cell death and survival,
      inflammation, and neo-angiogenesis. In the present review, we intend to shed
      light on the paradox of the coexisting healthy and toxic effects of n-3 PUFAs,
      focusing on their possible pro-oxidant cytotoxic and carcinogenic effect, in
      order to understand if their increased intake, recommended by a number of health
      agencies worldwide and promoted by nutraceutical producers, may or may not
      represent a hazard to human health.

PMID- 21902225
TI  - The free energy landscape analysis of protein (FIP35) folding dynamics.
AB  - A fundamental problem in the analysis of protein folding and other complex
      reactions is the determination of the reaction free energy landscape. The current
      experimental techniques lack the necessary spatial and temporal resolution to
      construct such landscapes. The properties of the landscapes can be probed only
      indirectly. Simulation, assuming that it reproduces the experimental dynamics,
      can provide the necessary spatial and temporal resolution. It is, arguably, the
      only way for direct rigorous construction of the quantitatively accurate free
      energy landscapes. Here, such landscape is constructed from the equilibrium
      folding simulation of FIP35 protein reported by Shaw et al. Science 2010, 330,
      341-346. For the dynamics to be accurately described as diffusion on the free
      energy landscape, the choice of reaction coordinates is crucial. The reaction
      coordinate used here is such that the dynamics projected on it is diffusive, so
      the description is consistent and accurate. The obtained landscape suggests an
      alternative interpretation of the simulation, markedly different from that of
      Shaw et al. In particular, FIP35 is not an incipient downhill folder, it folds
      via a populated on-pathway intermediate separated by high free energy barriers;
      the high free energy barriers rather than landscape roughness are a major
      determinant of the rates for conformational transitions; the preexponential
      factor of folding kinetics 1/k(0) ~ 10 ns rather than 1 MUs.

PMID- 21902226
TI  - Improvement of the quantification accuracy and throughput for phosphoproteome
      analysis by a pseudo triplex stable isotope dimethyl labeling approach.
AB  - Accurately quantifying the changes of phosphorylation level on specific sites is
      crucial to understand the role of protein phosphorylation in physiological and
      pathological processes. Here, a pseudo triplex stable isotope dimethyl labeling
      approach was developed to improve the accuracy and the throughput of
      comprehensive quantitative phosphoproteome analyses. In this strategy, two
      identical samples are labeled with light and heavy isotopes, respectively, while
      another comparative sample is labeled with an intermediate isotope. Two
      replicated quantification results were achieved in just one experiment, and the
      relative standard deviation (RSD) criterion was used to control the
      quantification accuracy. Compared with the conventional duplex labeling approach,
      the number of quantified phosphopeptides increased nearly 50% and the
      experimental time was reduced by 50% under the same quantification accuracy.
      Combined with the automated online reversed phase-strong cation exchange-reversed
      phase (RP-SCX-RP) multidimensional separation system, a comparative
      phosphoproteome analysis of hepatocellular carcinoma (HCC) and normal human liver
      tissues was performed. Over 1800 phosphopeptides corresponding to ~2000
      phosphorylation sites were quantified reliably in a 42 h multidimensional
      analysis. The pro-directed motifs, which were mainly associated with the
      extracellular signal-regulated kinases (ERKs), were observed as being
      overrepresented in the regulated phosphorylation sites, and some quantification
      results of phosphorylation sites were validated by the other studies. Therefore,
      this pseudo triplex labeling approach was demonstrated as a promising alternative
      for the comprehensive quantitative phosphoproteome analysis.

PMID- 21902228
TI  - Structure and excited-state proton transfer in the GFP S205A mutant.
AB  - To further explore excited state proton transfer (ESPT) pathways within green
      fluorescent protein (GFP), mutagenesis, X-ray crystallography, and time-resolved
      and steady-state optical spectroscopy were employed to create and study the GFP
      mutant S205A. In wild type GFP (wt-GFP), the proton transfer pathway includes the
      hydroxyl group of the chromophore, a water molecule, Ser205, and Glu222. We found
      that the ESPT rate constant of S205A is smaller by a factor of 20 than that of wt
      GFP and larger by a factor of 2 in comparison to the ESPT rate of S205V mutant
      which we previously characterized. (1)  High resolution crystal structures reveal
      that in both S205A and S205V mutants, an alternative proton transfer pathway is
      formed that involves the chromophore hydroxyl, a bridging water molecule, Thr203
      and Glu222. The slow PT rate is explained by the long (~3.2 A and presumably
      weak) hydrogen bond between Thr203 and the water molecule, compared to the 2.7 A
      normal hydrogen bond between the water molecule and Ser205 in wt-GFP. For data
      analysis of the experimental data from both GFP mutants, we used a two-rotamer
      kinetic model, assuming only one rotamer is capable of ESPT. Data analysis
      supports an agreement with the underlying assumption of this model.

PMID- 21902229
TI  - Adsorption of weak polyelectrolytes on charged nanoparticles. Impact of salt
      valency, pH, and nanoparticle charge density. Monte Carlo simulations.
AB  - Complex formation between a weak flexible polyelectrolyte chain and one
      positively charged nanoparticle in presence of explicit counterions and salt
      particles is investigated using Monte Carlo simulations. The influence of
      parameters such as the nanoparticle surface charge density, salt valency, and
      solution property such as the pH on the chain protonation/deprotonation process
      and monomer adsorption at the nanoparticle surface are systematically
      investigated. It is shown that the nanoparticle presence significantly modifies
      chain acid/base and polyelectrolyte conformational properties. The importance of
      the attractive electrostatic interactions between the chain and the nanoparticle
      clearly promotes the chain deprotonation leading, at high pH and nanoparticle
      charge density, to fully wrapped polyelectrolyte at the nanoparticle surface.
      When the nanoparticle bare charge is overcompensated by the polyelectrolyte
      charges, counterions and salt particles condense at the surface of the
      polyelectrolyte-nanoparticle complex to compensate for the excess of charges
      providing from the adsorbed polyelectrolyte chain. It is also shown that the
      complex formation is significantly affected by the salt valency. Indeed, with the
      presence of trivalent salt cations, competition is observed between the
      nanoparticle and the trivalent cations. As a result, the amount of adsorbed
      monomers is less important than in the monovalent and divalent case and chain
      conformations are different due to the collapse of polyelectrolyte segments
      around trivalent cations out of the nanoparticle adsorption layer.

PMID- 21902227
TI  - Mono- and dinuclear iron complexes of bis(1-methylimidazol-2-yl)ketone (bik):
      structure, magnetic properties, and catalytic oxidation studies.
AB  - The newly synthesized dinuclear complex [Fe(III)(2)(MU-OH)(2)(bik)(4)](NO(3))(4)
      (1) (bik, bis(1-methylimidazol-2-yl)ketone) shows rather short Fe...Fe (3.0723(6)
      A) and Fe-O distances (1.941(2)/1.949(2) A) compared to other unsupported
      Fe(III)(2)(MU-OH)(2) complexes. The bridging hydroxide groups of 1 are strongly
      hydrogen-bonded to a nitrate anion. The (57)Fe isomer shift (delta = 0.45 mm s(
      1)) and quadrupole splitting (DeltaE(Q) = 0.26 mm s(-1)) obtained from Mossbauer
      spectroscopy are consistent with the presence of two identical high-spin
      iron(III) sites. Variable-temperature magnetic susceptibility studies revealed
      antiferromagnetic exchange (J = 35.9 cm(-1) and H = JS(1).S(2)) of the metal
      ions. The optimized DFT geometry of the cation of 1 in the gas phase agrees well
      with the crystal structure, but both the Fe...Fe and Fe-OH distances are
      overestimated (3.281 and 2.034 A, respectively). The agreement in these
      parameters improves dramatically (3.074 and 1.966 A) when the hydrogen-bonded
      nitrate groups are included, reducing the value calculated for J by 35%.
      Spontaneous reduction of 1 was observed in methanol, yielding a blue
      [Fe(II)(bik)(3)](2+) species. Variable-temperature magnetic susceptibility
      measurements of [Fe(II)(bik)(3)](OTf)(2) (2) revealed spin-crossover behavior.
      Thermal hysteresis was observed with 2, due to a loss of cocrystallized solvent
      molecules, as monitored by thermogravimetric analysis. The hysteresis disappears
      once the solvent is fully depleted by thermal cycling. [Fe(II)(bik)(3)](OTf)(2)
      (2) catalyzes the oxidation of alkanes with t-BuOOH. High selectivity for
      tertiary C-H bond oxidation was observed with adamantane (3 degrees /2 degrees 
      value of 29.6); low alcohol/ketone ratios in cyclohexane and ethylbenzene
      oxidation, a strong dependence of total turnover number on the presence of O(2),
      and a low retention of configuration in cis-1,2-dimethylcyclohexane oxidation
      were observed. Stereoselective oxidation of olefins with dihydrogen peroxide
      yielding epoxides was observed under both limiting oxidant and substrate
      conditions.

PMID- 21902230
TI  - Discovery of potent, orally bioavailable phthalazinone bradykinin B1 receptor
      antagonists.
AB  - The bradykinin B1 receptor is rapidly induced upon tissue injury and
      inflammation, stimulating the production of inflammatory mediators resulting in
      plasma extravasation, leukocyte trafficking, edema, and pain. We have previously
      reported on sulfonamide and sulfone-based B1 antagonists containing a privileged
      bicyclic amine moiety leading to potent series of 2-oxopiperazines. The
      suboptimal pharmacokinetics and physicochemical properties of the oxopiperazine
      sulfonamides led us to seek B1 antagonists with improved druglike properties.
      Using a pharmacophore model containing a bicyclic amine as anchor, we designed a
      series of amide antagonists with targeted physicochemical properties. This
      approach led to a novel series of potent phthalazinone B1 antagonists, where we
      successfully replaced a sulfonamide acceptor with a cyclic carbonyl unit. SAR
      studies revealed compounds with subnanomolar B1 binding affinity. These compounds
      demonstrate excellent cross-species PK properties with high oral bioavailability
      and potent activity in a rabbit biochemical challenge pharmacodynamic study.

PMID- 21902231
TI  - Decorating diruthenium compounds with Frechet dendrons via the click reaction.
AB  - A series of dendronized-Ru(2) compounds were prepared using the Cu(I)-catalyzed
      1,3-dipolar cycloaddition (click reaction) between the terminal azides of
      azidopoly(benzyl ether) dendrons ([D(n)]-N(3), n = 0-3) and Ru(2) units bearing
      one or two terminal ethynes, Ru(2)(D(3,5-Cl(2)Ph)F)(4-m)(DMBA-4-C(2)H)(m)Cl with
      m = 1 and 2, and D(3,5-Cl(2)Ph)F and DMBA-4-C(2)H as N,N'-bis(3,5-dichloro
      phenyl)formamidinate and N,N'-dimethyl-4-ethynylbenzamidinate, respectively. The
      resultant Ru(2)(D(3,5-Cl(2)Ph)F)(4-m)(DMBA-D(n))(m)Cl compounds were further
      functionalized by the axial ligand displacement of Cl by -C(2)Ph to yield new
      compounds Ru(2)(D(3,5-Cl(2)Ph)F)(4-m)(DMBA-D(n))(m)(C(2)Ph)(2) (where m = 1 and
      2; n = 0 and 1). All Ru(2) compounds reported herein were analyzed via mass
      spectrometry, voltammetry, and UV-visible and fluorescence spectroscopy. Density
      functional theory (DFT) calculations were performed on a model compound to gain
      more insight into the molecular orbital energy levels possibly associated with
      the photophysical data obtained and presented herein.

PMID- 21902232
TI  - Synthesis and structure of dawson polyoxometalate-based, multifunctional,
      inorganic-organic hybrid compounds: organogermyl complexes with one terminal
      functional group and organosilyl analogues with two terminal functional groups.
AB  - Four novel multifunctional polyoxometalate (POM)-based inorganic-organic hybrid
      compounds, [alpha(2)-P(2)W(17)O(61){(RGe)}](7-) (Ge-1, R(1) = HOOC(CH(2))(2(-))
      and Ge-2, R(2) = H(2)C?CHCH(2(-))) and [alpha(2)-P(2)W(17)O(61){(RSi)(2)O}](6-)
      (Si-1, R(1) and Si-2, R(2)), were prepared by incorporating organic chains having
      terminal functional groups (carboxylic acid and allyl groups) into monolacunary
      site of Dawson polyoxoanion [alpha(2)-P(2)W(17)O(61)](10-). In these POMs, new
      modification of the terminal functional groups was attained by introducing
      organogermyl and organosilyl groups. Dimethylammonium salts of the organogermyl
      complexes, (Me(2)NH(2))(7)[alpha(2)-P(2)W(17)O(61)(R(1)Ge)].H(2)O MeN-Ge-1 and
      (Me(2)NH(2))(7)[alpha(2)-P(2)W(17)O(61)(R(2)Ge)].4H(2)O MeN-Ge-2, were obtained
      as analytically pure crystals, in 22.8% and 55.3% yields, respectively, by
      stoichiometric reactions of [alpha(2)-P(2)W(17)O(61)](10-) with separately
      prepared Cl(3)GeC(2)H(4)COOH in water, and H(2)C?CHCH(2)GeCl(3) in a solvent
      mixture of water/acetonitrile. Synthesis and X-ray structure analysis of the
      Dawson POM-based organogermyl complexes were first successful. Dimethylammonium
      salts of the corresponding organosilyl complexes, (Me(2)NH(2))(6)[alpha(2)
      P(2)W(17)O(61){(R(1)Si)(2)O}].4H(2)O MeN-Si-1 and (Me(2)NH(2))(6)[alpha(2)
      P(2)W(17)O(61){(R(2)Si)(2)O}].6H(2)O MeN-Si-2, were also obtained as analytically
      pure crystalline crystals, in 17.1% and 63.5% yields, respectively, by
      stoichiometric reactions of [alpha(2)-P(2)W(17)O(61)](10-) with
      NaOOC(CH(2))(2)Si(OH)(2)(ONa) and H(2)C?CHCH(2)Si(OEt)(3). These complexes were
      characterized by elemental analysis, thermogravimetric and differential thermal
      analyses (TG/DTA), FTIR, solid-state ((31)P) and solution ((31)P, (1)H, and
      (13)C) NMR, and X-ray crystallography.

PMID- 21902234
TI  - Triple quadrupole mass spectrometry for direct mixture analysis and structure
      elucidation.

PMID- 21902233
TI  - Synthesis of 2- and 2,3-substituted pyrazolo[1,5-a]pyridines: scope and
      mechanistic considerations of a domino direct alkynylation and cyclization of N
      iminopyridinium ylides using alkenyl bromides, alkenyl iodides, and alkynes.
AB  - Direct functionalization and tandem processes have both received considerable
      recent interest due to their cost and time efficiency. Herein we report the
      synthesis of difficult to obtain 2-substituted pyrazolo[1,5-a]pyridines through a
      tandem palladium-catalyzed/silver-mediated elimination/direct
      functionalization/cyclization reaction involving N-benzoyliminopyridinium ylides.
      As such, these biologically important molecules are prepared in an efficient,
      high-yielding manner, only requiring a two-step sequence from pyridine. Aryl
      substituted alkenyl bromides and iodides are effective ylide coupling partners.
      Mechanistic studies led to the use of terminal alkynes, which extended the scope
      of the reaction to include alkyl substitution on the unsaturated reactive site.
      The optimization, scope, and mechanistic considerations of the process are
      discussed.

PMID- 21902235
TI  - Synthesis and biological activity of 2-(3'-hydroxypropylidene)-1alpha-hydroxy-19
      norvitamin D analogues with shortened alkyl side chains.
AB  - As a continuation of our efforts directed to vitamin D compounds of promising
      biological properties, 19-norvitamins 9-13, possessing a 3'-hydroxypropylidene
      fragment attached to C-2 and shortened 17beta-alkyl chains, were synthesized. A
      new synthetic pathway providing the CD-ring ketones 20-24 is described starting
      from the epimeric aldehydes 25 and 26. The hydrindanones 20-24 were subjected to
      the Wittig-Horner reaction with the phosphine oxide 14, and the vitamin D
      compounds 9-13 were obtained after hydroxyl deprotection. In comparison to
      1alpha,25-(OH)(2)D(3) (1), the prepared analogues, except for the 20R-compound
      12, were only ca. 3 times less potent in binding to VDR. Compounds 9-11 and 13
      exhibited HL-60 cellular activity 5-20 times lower and transcriptional activity
      ca. 10 times decreased related to those for the hormone 1. When tested in vivo,
      all the analogues showed no ability to mobilize calcium from bone, and intestinal
      calcium transport activity was observed only at high doses of the vitamins 10,
      12, and 13.

PMID- 21902236
TI  - Investigation of a deoxyribozyme as a biofuel cell catalyst.
AB  - We examined the ability of a previously identified peroxidase deoxyribozyme to be
      employed as a catalyst in biofuel cells, as a possible replacement for
      oxidoreductase proteins. We constructed a biocathode using a covalently linked
      version of the peroxidase deoxyribozyme-hemin complex and successfully paired it
      with a glucose dehydrogenase-modified bioanode for power production.

PMID- 21902237
TI  - Surface plasmons reveal spin crossover in nanometric layers.
AB  - Nano-objects and thin films displaying molecular spin-crossover phenomena have
      recently attracted much attention. However, the investigation of spin crossover
      at reduced sizes is still a big challenge. Here we demonstrate that surface
      plasmon polariton waves propagating along the interface between a metal and a
      dielectric layer can be used to detect the spin-state changes in the latter with
      high sensitivity, even at the nanometer scale.

PMID- 21902238
TI  - N-Capping of primary amines with 2-acyl-benzaldehydes to give isoindolinones.
AB  - A unique reactivity pattern, first observed in the conversion of the marine
      natural product pestalone into pestalachloride A, was investigated. It was shown
      that 2-formyl-arylketones smoothly react with ammonia and primary amines,
      respectively, under mild conditions to afford 3-substituted isoindolinones in
      high yield. The reaction represents a new option for the derivatization (N
      capping) of primary amines. As the substrates are readily accessible the
      methodology opens a short and modular access to pharmaceutically relevant
      substituted isoindolinones.

PMID- 21902239
TI  - Water-repellent cellulose fiber networks with multifunctional properties.
AB  - We demonstrate a simple but highly efficient technique to introduce
      multifunctional properties to cellulose fiber networks by wetting them with ethyl
      cyanoacrylate monomer solutions containing various suspended organic
      submicrometer particles or inorganic nanoparticles. Solutions can be applied on
      cellulosic surfaces by simple solution casting techniques or by dip coating, both
      being suitable for large area applications. Immediately after solvent
      evaporation, ethyl-cyanoacrylate starts cross-linking around cellulose fibers
      under ambient conditions because of naturally occurring surface hydroxyl groups
      and adsorbed moisture, encapsulating them with a hydrophobic polymer shell.
      Furthermore, by dispersing various functional particles in the monomer solutions,
      hydrophobic ethyl-cyanoacrylate nanocomposites with desired functionalities can
      be formed around the cellulose fibers. To exhibit the versatility of the method,
      cellulose sheets were functionalized with different ethyl-cyanoacrylate
      nanocomposite shells comprising submicrometer wax or polytetrafluoroethylene
      particles for superhydophobicity, MnFe(2)O(4) nanoparticles for magnetic
      activity, CdSe/ZnS quantum dots for light emission, and silver nanoparticles for
      antimicrobial activity. Morphological and functional properties of each system
      have been studied by scanning and transmission electron microscopy, detailed
      contact angle measurements, light emission spectra and E. coli bacterial growth
      measurements. A plethora of potential applications can be envisioned for this
      technique, such as food and industrial packaging, document protection, catalytic
      cellulosic membranes, textronic (electrofunctional textiles), electromagnetic
      devices, authentication of valuable documents, and antimicrobial wound healing
      products to name a few.

PMID- 21902240
TI  - Design and facile solid-phase synthesis of conformationally constrained bicyclic
      peptoids.
AB  - Triazine-bridged bicyclic peptoids as conformationally constrained
      peptidomimetics are described. Bicyclic peptoids composed of 6-12 peptoid
      residues (m, n = 3-6) were synthesized in excellent yields using a highly
      efficient solid-phase synthetic route.

PMID- 21902241
TI  - A powerful cascade approach for expeditious synthesis of trifluoromethylated
      furans.
AB  - A powerful approach to synthesize trifluoromethylated furans has been developed.
      The method is operationally simple, broad in substrate scope, and amenable to
      scale-up using trifluoroacetic anhydride. Meanwhile, the strategy not only
      provided a versatile approach to synthesize trifluoromethylated furans but also
      provides a new method for exploring the new reactivity of trifluoroacetic
      anhydride.

PMID- 21902242
TI  - Hidden in plain sight: subtle effects of the 8-oxoguanine lesion on the
      structure, dynamics, and thermodynamics of a 15-base pair oligodeoxynucleotide
      duplex.
AB  - The base lesion 8-oxoguanine is formed readily by oxidation of DNA, potentially
      leading to G -> T transversion mutations. Despite the apparent similarity of 8
      oxoguanine-cytosine base pairs to normal guanine-cytosine base pairs, cellular
      base excision repair systems effectively recognize the lesion base. Here we apply
      several techniques to examine a single 8-oxoguanine lesion at the center of a
      nonpalindromic 15-mer duplex oligonucleotide in an effort to determine what, if
      anything, distinguishes an 8-oxoguanine-cytosine (8oxoG-C) base pair from a
      normal base pair. The lesion duplex is globally almost indistinguishable from the
      unmodified parent duplex using circular dichroism spectroscopy and ultraviolet
      melting thermodynamics. The DNA mismatch-detecting photocleavage agent
      Rh(bpy)(2)chrysi(3+) cleaves only weakly and nonspecifically, revealing that the
      8oxoG-C pair is locally stable at the level of the individual base pairs. Nuclear
      magnetic resonance spectra are also consistent with a well-conserved B-form
      duplex structure. In the two-dimensional nuclear Overhauser effect spectra, base
      sugar and imino-imino cross-peaks are strikingly similar between parent and
      lesion duplexes. Changes in chemical shift due to the 8oxoG lesion are localized
      to its complementary cytosine and to the 2-3 bp immediately flanking the lesion
      on the lesion strand. Residues further removed from the lesion are shown to be
      unperturbed by its presence. Notably, imino exchange experiments indicate that
      the 8-oxoguanine-cytosine pair is strong and stable, with an apparent equilibrium
      constant for opening equal to that of other internal guanine-cytosine base pairs,
      on the order of 10(-6). This collection of experiments shows that the 8
      oxoguanine-cytosine base pair is incredibly stable and similar to the native
      pair.

PMID- 21902243
TI  - Synthesis of amino-benzothiaoxazepine-1,1-dioxides utilizing a microwave
      assisted, S(N)Ar protocol.
AB  - The development of a microwave-assisted, intermolecular S(N)Ar protocol for the
      synthesis of a 126-member benzothiaoxazepine-1,1-dioxide library is reported.
      Diversification of 12 benzothiaoxazepine-1,1-dioxides was achieved in rapid
      fashion utilizing a variety of 2 degrees  amines and amino alcohols to generate
      an 80-member library. A second 48-member library was subsequently generated via a
      two-step alkylation, intermolecular S(N)Ar diversification protocol.

PMID- 21902246
TI  - In-situ measurement of electroosmotic drag coefficient in Nafion membrane for the
      PEMFC.
AB  - A new method based on hydrogen pump has been developed to measure the
      electroosmotic drag coefficient in representative PEMFC operating conditions. It
      allows eliminating the back-flow of water which leads to some errors in the
      calculation of this coefficient with previously reported electrochemical methods.
      Measurements have been performed on 50 MUm thick Nafion membranes both extruded
      and recast. Contrary to what has been described in most of previous published
      works, the electroosmotic drag coefficient decreases as the membrane water
      content increases. The same trend is observed for temperatures between 25 and 80 
      degrees C. For the same membrane water content, the electroosmotic drag
      coefficient increases with temperature. In the same condition, there is no
      difference in drag coefficient for extruded Nafion N112 and recast Nafion NRE212.
      These results are discussed on the basis of the two commonly accepted proton
      transport mechanisms, namely, Grotthus and vehicular.

PMID- 21902245
TI  - Total synthesis and biological evaluation of pederin, psymberin, and highly
      potent analogs.
AB  - The potent cytotoxins pederin and psymberin have been prepared through concise
      synthetic routes (10 and 14 steps in the longest linear sequences, respectively)
      that proceed via a late-stage multicomponent approach to construct the N-acyl
      aminal linkages. This route allowed for the facile preparation of a number of
      analogs that were designed to explore the importance of the alkoxy group in the N
      acyl aminal and functional groups in the two major subunits on biological
      activity. These analogs, including a pederin/psymberin chimera, were analyzed for
      their growth inhibitory effects, revealing several new potent cytotoxins and
      leading to postulates regarding the molecular conformational and hydrogen bonding
      patterns that are required for biological activity. Second generation analogs
      have been prepared based on the results of the initial assays and a structure
      based model for the binding of these compounds to the ribosome. The growth
      inhibitory properties of these compounds are reported. These studies show the
      profound role that organic chemistry in general and specifically late-stage
      multicomponent reactions can play in the development of unique and potent
      effectors for biological responses.

PMID- 21902244
TI  - Biosynthesis of cholesterol and other sterols.

PMID- 21902247
TI  - Enhanced reductive dechlorination of polychlorinated biphenyl impacted sediment
      by bioaugmentation with a dehalorespiring bacterium.
AB  - Anaerobic reductive dehalogenation of commercial PCBs such as Aroclor 1260 has a
      critical role of transforming highly chlorinated congeners to less chlorinated
      congeners that are then susceptible to aerobic degradation. The efficacy of
      bioaugmentation with the dehalorespiring bacterium Dehalobium chlorocoercia DF1
      was tested in 2-L laboratory mesocosms containing sediment contaminated with
      weathered Aroclor 1260 (1.3 ppm) from Baltimore Harbor, MD. Total penta- and
      higher chlorinated PCBs decreased by approximately 56% (by mass) in bioaugmented
      mesocosms after 120 days compared with no activity observed in unamended
      controls. Bioaugmentation with DF-1 enhanced the dechlorination of doubly flanked
      chlorines and stimulated the dechlorination of single flanked chlorines as a
      result of an apparent synergistic effect on the indigenous population. Addition
      of granulated activated carbon had a slight stimulatory effect indicating that
      anaerobic reductive dechlorination of PCBs at low concentrations was not
      inhibited by a high background of inorganic carbon that could affect
      bioavailability. The total number of dehalorespiring bacteria was reduced by
      approximately half after 60 days. However, a steady state level was maintained
      that was greater than the indigenous population of putative dehalorespiring
      bacteria in untreated sediments and DF1 was maintained within the indigenous
      population after 120 days. The results of this study demonstrate that
      bioaugmentation with dehalorespiring bacteria has a stimulatory effect on the
      dechlorination of weathered PCBs and supports the feasibility of using in situ
      bioaugmentation as an environmentally less invasive and lower cost alternate to
      dredging for treatment of PCB impacted sediments.

PMID- 21902248
TI  - Abilities of different electron donors (D) to engage in a P...D noncovalent
      interaction.
AB  - Previous work has documented the ability of the P atom to form a direct
      attractive noncovalent interaction with a N atom, based in large measure on the
      charge transfer from the N lone pair into the sigma* antibonding orbital of the P
      H that is turned away from the N atom. The present work considers whether other
      atoms, namely, O and S, can also participate as electron donors, and in which
      bonding environments. Also considered are the pi-systems of multiply bonded C
      atoms. Unlike an earlier observation that the interaction is unaffected by the
      nature of the electron-acceptor atom, there is strong sensitivity to the donor.
      The P...D binding energy diminishes in the order D = NH(3) > H(2)CO > H(2)CS >
      H(2)O > H(2)S, different from the patterns observed in both H and halogen bonds.
      The P...D interactions are comparable to, and in some cases stronger than, the
      analogous H-bonds formed by HOH as proton donor. The carbon pi systems form
      surprisingly strong P...D complexes, augmented by the back-donation from the P
      lone pair to the C-C pi* antibond, which surpass the strengths of H-bonds, even
      some with HF as proton donor.

PMID- 21902249
TI  - Efficient blue-emitting Ir(III) complexes with phosphine carbanion-based
      ancillary ligand: a DFT study.
AB  - We report a theoretical study on a series of heteroleptic cyclometalated Ir(III)
      complexes for OLED application. The geometries, electronic structures, and the
      lowest-lying singlet absorptions and triplet emissions of
      [(fppy)(2)Ir(III)(PPh(2)Np)] (1), and theoretically designed models
      [(fppy)(2)Ir(III)(PH(2)Np)] (2) and [(fppy)(2)Ir(III)Np](-)(3) were investigated
      with density functional theory (DFT)-based approaches, where, fppyH = 4
      fluorophenyl-pyridine and NpH = naphthalene. The ground and excited states were,
      respectively, optimized at the M062X/LanL2DZ;6-31G* and CIS/LanL2DZ:6-31G* level
      of theory within CH(2)Cl(2) solution provided by PCM. The lowest absorptions and
      emissions were evaluated at M062X/Stuttgart;cc-pVTZ;cc-pVDZ level of theory.
      Though the lowest absorptions and emissions were all attributed as the ligand
      based charge-transfer transition with slight metal-to-ligand charge-transfer
      transition character, the subtle differences in geometries and electronic
      structures result in the different quantum yields and versatile emission color.
      The newly designed molecular 3 is expected to be highly emissive in deep blue
      region.

PMID- 21902250
TI  - The cardiovascular risk of healthy individuals studied by NMR metabonomics of
      plasma samples.
AB  - The identification and the present wide acceptance of cardiovascular risk factors
      such as age, sex, hypertension, hyperlipidemia, smoking, obesity, diabetes, and
      physical inactivity have led to dramatic reductions in cardiovascular morbidity
      and mortality. However, novel risk predictors present opportunities to identify
      more patients at risk and to more accurately define the biochemical signature of
      that risk. In this paper, we present a comprehensive metabonomic analysis of 864
      plasma samples from healthy volunteers, through Nuclear Magnetic Resonance (NMR)
      and multivariate statistical analysis (regression and classification). We have
      found that subjects that are classified as at high or at low risk using the
      common clinical markers can also be discriminated using NMR metabonomics. This
      discrimination is not only due to common markers (such as total cholesterol,
      triglycerides, LDL, HDL), but also to (p < 0.05 after Bonferroni correction)
      other metabolites (e.g., 3-hydroxybutyrate, alpha-ketoglutarate, threonine,
      dimethylglycine) previously not associated with cardiovascular diseases.

PMID- 21902251
TI  - Efficient identification of different types of carbons in organic solids by 2D
      solid-state NMR spectroscopy.
AB  - An efficient method for identifying different types of carbon groups (CH(3),
      CH(2), CH, and quaternary carbons) in organic solids is proposed by utilizing the
      combination of a two-dimensional (2D) (13)C-(1)H polarization inversion spin
      exchange at magic angle (PISEMA) NMR experiment and numerical simulation results
      of simple isolated (13)C-(1)H dipolar coupling models. Our results reveal that
      there is a unique line shape of the (13)C-(1)H dipolar splitting pattern and a
      corresponding characteristic splitting value for each carbon group, based on
      which different carbon types can be distinguished unambiguously. In particular,
      by using this method, the discrimination and assignment of overlapped signals
      from different types of carbons can be achieved easily. The efficacy of this
      method is demonstrated on typical solid small molecules, polymers, and
      biomacromolecules.

PMID- 21902252
TI  - Organization of glucose-responsive systems and their properties.

PMID- 21902253
TI  - Studies on the encapsulation of various anions in different fullerenes using
      density functional theory calculations and Born-Oppenheimer molecular dynamics
      simulation.
AB  - The density functional theory (DFT)-based Becke's three parameter hybrid exchange
      functional and Lee-Yang-Parr correlation functional (B3LYP) calculations and Born
      Oppenheimer molecular dynamics (BOMD) simulations have been performed to
      understand the stability of different anions inside fullerenes of various sizes.
      As expected, the stability of anion inside the fullerene depends on its size as
      well as on the size of the fullerene. Results show that the encapsulation of
      anions in larger fullerenes (smaller fullerene) is energetically favorable (not
      favorable). The minimum size of the fullerene required to encapsulate F(-) is
      equal to C(32). It is found from the results that C(60) can accommodate F(-), Cl(
      ), Br(-), OH(-), and CN(-). The electron density topology analysis using atoms in
      molecule (AIM) approach vividly delineates the interaction between fullerene and
      anion. Although F(-)@C(30) is energetically not favorable, the BOMD results
      reveal that the anion fluctuates around the center of the cage. The anion does
      not exhibit any tendency to escape from the cage.

PMID- 21902254
TI  - Anisotropic water reorientation around ions.
AB  - We study the reorientation dynamics of water molecules around ions using
      terahertz dielectric relaxation spectroscopy and polarization-resolved
      femtosecond infrared pump-probe spectroscopy. The results are discussed in
      relation to the ion-specific Hofmeister series and the concomitant "structure
      making" and "structure-breaking" effects of ions on water. We show that when a
      dissolved salt consists of a strongly hydrated ion with a weakly hydrated
      counterion the reorientation of water molecules around the strongly hydrated ion
      is anisotropic, in the sense that differently charged ions affect reorientation
      along different molecular axes: cations mainly slow the reorientation dynamics of
      the water dipole vectors, and anions mainly slow down the reorientation dynamics
      of the hydroxyl group that points toward the anion. In both cases, motion along
      only one molecular axis is impeded, so that the hydration shell is best described
      as semirigid. In this semirigid hydration picture, water molecules in the first
      hydration shell show anisotropic reorientation, whereas water molecules outside
      the first hydration shell remain unaffected. The inferred anisotropy in molecular
      motion explains why terahertz dielectric relaxation spectroscopy, which probes
      dipolar relaxation, is more sensitive to cation hydration effects while
      femtosecond infrared pump-probe spectroscopy, which is sensitive to reorientation
      of hydroxyl groups, is more sensitive to anion hydration effects. We also show
      that dissolution of CsI-a salt for which both cation and anion are weakly
      hydrated-has little effect on water reorientation dynamics, with hydration water
      displaying dynamics that are similar to those in bulk water.

PMID- 21902255
TI  - Brominated flame retardants in the atmosphere of E-waste and rural sites in
      southern China: seasonal variation, temperature dependence, and gas-particle
      partitioning.
AB  - The recycling of electrical and electronic waste(e-waste) in developing countries
      has attracted much attention as a significant source of brominated flame
      retardants (BFRs).Gaseous and particle-bound BFRs were measured in the atmosphere
      at e-waste and rural sites in southern China during 2007-2008. The annual average
      concentrations in the air were 3260 +/- 3370 and 219 +/- 192 pg/m3 for
      polybrominated diphenyl ethers (PBDEs) and were 546 +/- 547 and 165 +/- 144 pg/m3
      for non-PBDE BFRs at the e-waste and rural sites,respectively. PBDEs had
      unusually high relative concentrations of di- and tribrominated congeners at the
      e-waste site. The Clausius-Clapeyron (CC) plots showed that the gaseous
      concentrations of less brominated BFRs (di- through hexa-BFRs) were strongly
      controlled by temperature-driven evaporation from contaminated surfaces (e.g., e
      waste, soils, and recycled e-waste remains) except for winter. However, weak
      temperature dependence at the rural site suggests that regional or long-range
      atmospheric transport was largely responsible for the air concentrations. Gas
      particle partitioning (KP) of PBDEs correlated well with the subcooled liquid
      vapor pressure (PL(o)) for most sampling events. The varied slopes of log KP
      versus log PL(o) plots for the e-waste site (-0.59 to -1.29) indicated an
      influence of ambient temperature and atmospheric particle properties on the
      partitioning behavior of BFRs. The flat slopes (-0.23 to -0.80) for the rural
      site implied an absorption-dominant partitioning. This paper suggests that e
      waste recycling in Asian low-latitude regions is a significant source of less
      brominated BFRs and has important implications for their global transport from
      warm to colder climate

PMID- 21902256
TI  - Pyochelin enantiomers and their outer-membrane siderophore transporters in
      fluorescent pseudomonads: structural bases for unique enantiospecific
      recognition.
AB  - Pyochelin (Pch) and enantiopyochelin (EPch) are enantiomeric siderophores, with
      three chiral centers, produced under iron limitation conditions by Pseudomonas
      aeruginosa and Pseudomonas fluorescens , respectively. After iron chelation in
      the extracellular medium, Pch-Fe and EPch-Fe are recognized and transported by
      their specific outer-membrane transporters: FptA in P. aeruginosa and FetA in P.
      fluorescens . Structural analysis of FetA-EPch-Fe and FptA-Pch-Fe, combined with
      mutagenesis and docking studies revealed the structural basis of the
      stereospecific recognition of these enantiomers by their respective transporters.
      Whereas FetA and FptA have a low sequence identity but high structural homology,
      the Pch and EPch binding pockets do not share any structural homology, but
      display similar physicochemical properties. The stereospecific recognition of
      both enantiomers by their corresponding transporters is imposed by the
      configuration of the siderophore's C4'' and C2'' chiral centers. This recognition
      involves specific hydrogen bonds between the Arg91 guanidinium group and EPch-Fe
      for FetA and between the Leu117-Leu116 main chain and Pch-Fe for FptA. FetA and
      FptA are the first membrane receptors to be structurally described with opposite
      binding enantioselectivities for their ligands, giving insights into the
      structural basis of their enantiospecificity.

PMID- 21902257
TI  - Pressure induced isostructural metastable phase transition of ammonium nitrate.
AB  - The energetic material ammonium nitrate (AN, NH(4)NO(3)) has been studied under
      both hydrostatic and nonhydrostatic conditions using diamond anvil cells combined
      with micro-Raman spectroscopy and synchrotron X-ray powder diffraction. The
      refined powder X-ray data indicates that under hydrostatic conditions AN-IV
      (orthorhombic, Pmmn) is stable to above 40 GPa. In one nonhydrostatic compression
      experiment a volume collapse was observed, suggesting an isostructural phase
      transition to a "metastable" phase IV' between 17 and 28 GPa. The structures of
      phase IV and IV' are similar with the subtle difference in the hydrogen-bonding
      network; that is, a noticeably shorter N1...O1 distance seen in phase IV'. This
      hydrogen bond has a significant component along the b-axis, which proves to be
      the most compressible until cell axis over the entire pressure range. It is
      likely that the shear stress of the nonhydrostatic experiment drives the phase IV
      to-IV' transition to occur. We compare the present isotherms of phase IV and IV'
      in both static and nonhydrostatic conditions with the previously obtained
      Hugoniot and find that the nonhydrostatic isotherm approximately matches the
      Hugoniot. On the basis of this comparison, we conjecture that a chemical reaction
      or phase transition may occur in AN under dynamic pressure conditions at 22 GPa.

PMID- 21902258
TI  - Complex dendrimer-lyotropic liquid crystalline systems: structural behavior and
      interactions.
AB  - The incorporation of dendrimer into three lyotropic liquid crystalline (LLCs)
      mesophases is demonstrated for the first time. A second generation (G2) of
      poly(propylene imine) dendrimer (PPI) was solubilized into lamellar, diamond
      reverse cubic, and reverse hexagonal LLCs composed of glycerol monooleate (GMO),
      and water (and D-alpha-tocopherol in the H(II) system). The combination of PPI
      with LLCs may provide an advantageous drug delivery system. Cross-polarized light
      microscope, small-angle X-ray scattering (SAXS), and attenuated total reflectance
      Fourier transform infrared (ATR-FTIR) were utilized to study the structural
      behavior of the mesophases, the localization of PPI within the system, and the
      interactions between the guest molecule and the system's components. It was
      revealed that PPI-G2 functioned as a "water pump", competing with the lipid
      headgroups for water binding. As a result, L(alpha)->H(II) and Q(224)->H(II)
      structural shifts were detected (at 10 wt % PPI-G2 content), probably caused by
      the dehydration of monoolein headgroups and subsequent increase of the lipid's
      critical packing parameter (CPP). In the case of H(II), as a result of the
      balance between the dehydration of the monoolein headgroups and the significant
      presence of PPI within the interfacial region, increasing the quantity of
      hydrogen bonds, no structural transitions occurred. ATR-FTIR analysis
      demonstrated a downward shift of the H-O-H (water), as a result of PPI-G2
      embedment, suggesting an increase in the mean water-water H-bond angle resulting
      from binding PPI-G2 to the water network. Additionally, the GMO hydroxyl groups
      at beta- and gamma-C-OH positions revealed a partial interaction of hydrogen
      bonds with N-H functional groups of the protonated PPI-G2. Other GMO interfacial
      functional groups were shown to interact with the PPI-G2, in parallel with the
      GMO dehydration phenomenon. In the future, these outcomes can be used to design
      advanced drug delivery systems, allowing administration of dendrimers as a
      therapeutic agent from LLCs.

PMID- 21902259
TI  - Modification of proteins with cyclodextrins prevents aggregation and surface
      adsorption and increases thermal stability.
AB  - This work describes a general approach for preventing protein aggregation and
      surface adsorption by modifying proteins with beta-cyclodextrins (betaCD) via an
      efficient water-driven ligation. As compared to native unmodified proteins, the
      cyclodextrin-modified proteins (lysozyme and RNase A) exhibit significant
      reduction in aggregation, surface adsorption and increase in thermal stability.
      These results reveal a new chemistry for preventing protein aggregation and
      surface adsorption that is likely of different mechanisms than that by modifying
      proteins with poly(ethylene glycol).

PMID- 21902260
TI  - Polyethylenimine-impregnated mesoporous silica: effect of amine loading and
      surface alkyl chains on CO2 adsorption.
AB  - Poly(ethyleneimine) (PEI) supported on pore-expanded MCM-41 whose surface is
      covered with a layer of long-alkyl chains was found to be a more efficient CO(2)
      adsorbent than PEI supported on the corresponding calcined silica and all PEI
      impregnated materials reported in the literature. The layer of surface alkyl
      chains plays an important role in enhancing the dispersion of PEI, thus
      decreasing the diffusion resistance. It was also found that at low temperature,
      adsorbents with relatively low PEI contents are more efficient than their highly
      loaded counterparts because of the increased adsorption rate. Extensive CO(2)
      adsorption-desorption cycling showed that the use of humidified feed and purge
      gases affords materials with enhanced stability, despite limited loss due to
      amine evaporation.

PMID- 21902261
TI  - Study of polymorphism of 4-hexyl-4'-isothiocyanatobiphenyl by complementary
      methods.
AB  - The results of adiabatic calorimetry, mid-infrared spectroscopy, X-ray
      diffraction, and polarized microscopy of 4-hexyl-4'-isothiocyanatobiphenyl are
      presented. Apart from the well-known isotropic liquid and smectic phases,
      calorimetric measurements indicate the existence of two stable crystalline
      phases. Quantitative analysis of infrared bands enabled the determination of
      phase transitions, observation of crystallization kinetics, and elucidation of
      the glass transition of the crystal-like smectic E phase. The structural
      information about the glass of the smectic E obtained from the diffraction
      studies is complemented by textures recorded by polarized microscopy.

PMID- 21902262
TI  - Ionic strength effects on silicic acid (H4SiO4) sorption and oligomerization on
      an iron oxide surface: an interesting interplay between electrostatic and
      chemical forces.
AB  - The effect of ionic strength on reactions at aqueous interfaces can provide
      insights into the nature of the chemistry involved. The adsorption of H(4)SiO(4)
      on iron oxides at low surface silicate concentration (Gamma(Si)) forms monomeric
      silicate complexes with Fe-O-Si linkages, but as Gamma(Si) increases silicate
      oligomers with Si-O-Si linkages become increasingly prevalent. In this paper, the
      effect of ionic strength (I) on both Gamma(Si) and the extent of silicate
      oligomerization on the ferrihydrite surface is determined at pH 4, 7, and 10,
      where the surface is, respectively, positive, nearly neutral, and negatively
      charged. At pH 4, an increase in ionic strength causes Gamma(Si) to decrease at a
      given H(4)SiO(4) solution concentration, while the proportion of oligomers on the
      surface at a given Gamma(Si) increases. At pH 10, the opposite is observed;
      Gamma(Si) increases as I increases, while the proportion of surface oligomers at
      a given Gamma(Si) decreases. Ionic strength has only a small effect on the
      surface chemistry of H(4)SiO(4) at pH 7, but at low Gamma(Si) this effect is in
      the direction observed at pH 4 while at high Gamma(Si) the effect is in the
      direction observed at pH 10. The pH where the surface has zero charge decreases
      from ~8 to 6 as Gamma(Si) increases so that the surface potential (Psi) is
      positive at pH 4 for all Gamma(Si) and at pH 7 with low Gamma(Si). Likewise, Psi
      < 0 at pH 10 for all Gamma(Si) and at pH 7 with high Gamma(Si). The diffuse layer
      model is used to unravel the complex and subtle interactions between surface
      potential (Psi) and chemical parameters that influence interfacial silicate
      chemistry. This analysis reveals that the decrease in the absolute value of Psi
      as I increases causes Gamma(Si) to decrease or increase where Psi is,
      respectively, positive or negative. Therefore, at a given Gamma(Si), the solution
      H(4)SiO(4) concentration changes with I, and because oligomerization has a higher
      H(4)SiO(4) stoichiometry coefficient than monomer adsorption, this results in the
      observed dependence of the extent of silicate oligomerization on I.

PMID- 21902263
TI  - Zwitterionic polymersomes in an ionic liquid: room temperature TEM
      characterization.
AB  - Conventional transmission electron microscopy (TEM) was utilized to characterize
      vesicles formed by the spontaneous self-assembly of a novel zwitterionic block
      copolymer in the ionic liquid (2-hydroxyethyl)dimethylammonium methanesulfonate
      as well as in 0.1 M phosphate buffered saline (PBS). This block copolymer was
      synthesized via ring-opening metathesis polymerization (ROMP) of a norbornene
      based sulfobetaine, followed by its end-functionalization with polystyrene to
      generate the necessary amphiphilic structure. The ionic liquid enabled the
      visualization of the vesicles in their swollen state by TEM, demonstrating a new
      method for improved characterization of polymer vesicles.

PMID- 21902264
TI  - Self-organized poly(n-octadecylsilsesquioxane) films via sol-gel
      photopolymerization.
AB  - We describe a novel solvent- and water-free sol-gel process for n
      octadecyltriclorosilane (C(18)H(37)SiCl(3)) film catalyzed by photogenerated
      Bronsted acids. Driven by hydrophobic van der Waals interactions, a photoinduced
      self-assembly process occurs to afford a long-range ordered lamellar
      mesostructure, characterized by X-ray diffraction and transmission electron
      microscopy. Real-time Fourier transform IR spectroscopy was instrumental to probe
      the fast hydrolysis kinetics and assess the change of conformational behavior of
      the alkyl chains during UV irradiation. A unique combination of different solid
      state NMR techniques ((29)Si, (13)C, (1)H) provided an insight into the
      supramolecular organization of this hybrid film.

PMID- 21902265
TI  - Impact dynamics of colloidal quantum dot solids.
AB  - We use aerosol techniques to investigate the cohesive and granular properties of
      solids composed of colloidal semiconductor nanocrystals (quantum dot solids). We
      form spherical agglomerates of nanocrystals with a nebulizer and direct them
      toward a carbon substrate at low (~0.01 m/s) or high (~100 m/s) velocities. We
      then study the morphology of the deposit (i.e., the "splat") after impact. By
      varying the size of the agglomerate and the spacing between the nanocrystals
      within it, we observe influences on the mechanical properties of the quantum dot
      solid. We observe a liquid-to-solid transition as the nanocrystals become more
      densely packed. Agglomerates with weakly interacting nanocrystals exhibit
      liquidlike splashing and coalescence of overlapping splats. More dense
      agglomerates exhibit arching and thickening effects, which is behavior typical of
      granular materials.

PMID- 21902266
TI  - Phenoxy radical (C6H5O) formation under single collision conditions from reaction
      of the phenyl radical (C6H5, X2A1) with molecular oxygen (O2, X3Sigmag(-)): the
      final chapter?
AB  - The combustion relevant elementary reaction of photolytically generated phenyl
      radicals (C(6)H(5), X(2)A(1)) with molecular oxygen to form the phenoxy radical
      (C(6)H(5)O) plus a ground state oxygen atom was investigated under single
      collision conditions at a collision energy of 21.2 +/- 0.9 kJ mol(-1). The
      reaction was found to proceed indirectly via the involvement of a long-lived
      phenylperoxy radical (C(6)H(5)O(2)) intermediate that decomposed via a rather
      loose exit transition state. In comparison with crossed beams data obtained
      previously at elevated collision energies, we suggest that, as the collision
      energy rises from 21 to 107 kJ mol(-1), the lifetime of the C(6)H(5)O(2) reaction
      intermediate decreases, that is, a classical behavior within the osculating
      complex model.

PMID- 21902267
TI  - Surfactant-induced aggregation patterns of thiazole orange: a photophysical
      study.
AB  - The aggregation behavior of the DNA marker dye thiazole orange (TO), has been
      investigated in two types of surfactant assemblies, namely, premicelles/micelles
      of sodium dodecyl sulfate (SDS) and pre reverse micelles/reverse micelles of
      sodium bis(2-ethylhexyl) sulfosuccinate (AOT). In the case of an SDS/water
      system, absorption spectral changes of TO signify the formation of H-aggregates
      and H-dimers of the dye at premicellar concentrations, which subsequently convert
      to the monomeric form beyond the critical micellar concentration (cmc).
      Interestingly, the observed changes in the absorption and emission
      characteristics due to the surfactant-induced formation of H-aggregates/dimers of
      TO are found to be useful to estimate the surfactant concentration parameters for
      premicellar aggregation of SDS. In the case of an AOT/n-heptane system,
      similarly, H-aggregates/dimers are observed at low AOT concentrations, below the
      cmc. However, in this case, the H-dimers persist even beyond the cmc. This is
      attributed to the strong tendency of TO for self-aggregation and its favorable
      electrostatic interactions with the AOT head groups. With increasing water
      content in the AOT reverse micelles, the hydration of the dye leads to the
      conversion of H-dimers to the monomeric form. The steady-state fluorescence
      results are nicely corroborated with those from time-resolved fluorescence
      studies and demonstrate the interesting behavior of the surfactant-induced
      aggregation of TO dye.

PMID- 21902268
TI  - Fabrication of silver patterns on polyimide films based on solid-phase
      electrochemical constructive lithography using ion-exchangeable precursor layers.
AB  - We report a fully additive-based electrochemical approach to the site-selective
      deposition of silver on a polyimide substrate. Using a cathode coated with ion
      doped precursor polyimide layers, patterns of metal masks used as anodes were
      successfully reproduced at the cathode-precursor interface through
      electrochemical and ion-exchange reactions, which resulted in the generation of
      silver patterns on the polyimide films after subsequent annealing and removal
      from the substrate. Excellent interfacial adhesion was achieved through metal
      nanostructures consisting of interconnecting silver nanoparticles at the metal
      polymer interface, which are electrochemically grown "in" the precursor layer.
      This approach is a resist- and etch-free process and thus provides an effective
      methodology toward lower-cost and high-throughput microfabrication.

PMID- 21902269
TI  - Dissociation dynamics of asymmetric alkynyl(aryl)iodonium radicals: an ab initio
      DRC approach to predict the surface functionalization selectivity.
AB  - The dissociation process of neutral open-shell [4-F-(C(6)H(4))-I-C=C-(CH(2))(4)
      Cl] and [4-NO(2)-(C(6)H(4))-I-C=C-(CH(2))(4)-Cl] asymmetric iodonium radicals was
      studied theoretically. Vertical electron affinities and DRC (dynamic reaction
      coordinate) results were obtained and compared with experimental evidence. In
      particular, the fluorine and nitro substituent groups were selected because of
      (i) their opposite electron-withdrawing/electron-donating effects and (ii)
      experimental evidence that the grafting ability, in terms of alkynyl/aryl
      grafting ratio, increases with decreasing electron-withdrawing nature of the para
      position substituent on the phenyl ring. DRC results show that the dissociation
      dynamics of the iodine-alkynyl carbon bond, for the nitro-substituted iodonium,
      occurs on a longer time scale than that of the fluorine-substituted iodonium.
      This finding is in agreement with the overall experimental results.

PMID- 21902270
TI  - High performance Na-doped PbTe-PbS thermoelectric materials: electronic density
      of states modification and shape-controlled nanostructures.
AB  - Thermoelectric heat-to-power generation is an attractive option for robust and
      environmentally friendly renewable energy production. Historically, the
      performance of thermoelectric materials has been limited by low efficiencies,
      related to the thermoelectric figure-of-merit ZT. Nanostructuring thermoelectric
      materials have shown to enhance ZT primarily via increasing phonon scattering,
      beneficially reducing lattice thermal conductivity. Conversely, density-of-states
      (DOS) engineering has also enhanced electronic transport properties. However,
      successfully joining the two approaches has proved elusive. Herein, we report a
      thermoelectric materials system whereby we can control both nanostructure
      formations to effectively reduce thermal conductivity, while concurrently
      modifying the electronic structure to significantly enhance thermoelectric power
      factor. We report that the thermoelectric system PbTe-PbS 12% doped with 2% Na
      produces shape-controlled cubic PbS nanostructures, which help reduce lattice
      thermal conductivity, while altering the solubility of PbS within the PbTe matrix
      beneficially modifies the DOS that allow for enhancements in thermoelectric power
      factor. These concomitant and synergistic effects result in a maximum ZT for 2%
      Na-doped PbTe-PbS 12% of 1.8 at 800 K.

PMID- 21902272
TI  - Metal-free cascade intramolecular S-arylation: regioselective synthesis of
      substituted benzothiazoles.

PMID- 21902271
TI  - Reversible controlled assembly of thermosensitive polymer-coated gold
      nanoparticles.
AB  - Aggregation of thermosensitive polymer-coated gold nanoparticles was performed in
      aqueous solution in the presence of a triblock copolymer poly(ethylene oxide)
      block-poly(propylene oxide)-block-poly(ethylene oxide) (Pluronic P123, PEO(20)
      PPO(68)-PEO(20)). The gold nanoparticles, AuNPs, which are covered by
      thermosensitive statistical copolymers poly(EO(x)-st-PO(y)), aggregate when the
      temperature is higher than the phase transition temperature of the polymer,
      leading to a macroscopic precipitation. The presence of Pluronic chains in
      solution prevents the uncontrolled aggregation of the AuNPs at higher temperature
      than both the aggregation temperature of the AuNPs (T(agg)) and the critical
      micellization temperature (cmt) of the Pluronic. The size, the colloidal
      stability, and the optical properties of the AuNPs aggregates are modulated as a
      function of the P123-to-AuNP ratio, which constitutes the critical parameter of
      the system. Moreover, the AuNP aggregation is totally reversible upon decreasing
      the temperature below T(agg). Our approach constitutes an easy way to the
      formation of well-controlled nanoparticle aggregates with well-defined sizes. The
      resulting aggregates have been characterized by UV-vis spectroscopy, dynamic
      light scattering, and electron microscopy.

PMID- 21902273
TI  - Modeling self-diffusion of simple fluids in nanopores.
AB  - The recent frictional model of the transport of fluid mixtures in nanopores
      developed in this laboratory is extended here to formulate a new theory of the
      self-diffusion of Lennard-Jones fluids in cylindrical pores by considering the
      problem of diffusion of identical molecules that differ only in color. The new
      theory is found to predict the self-diffusivity accurately over a wide range of
      densities and pore sizes, extending from molecularly narrow pores to large
      mesopores. However, deviations from the theory appear near to the critical
      temperature where the correlation length of the fluid diverges and when
      intermolecular interactions are important in molecularly narrow pores. Under such
      circumstances, local averaging of the fluid-fluid density to obtain a local
      viscosity does not adequately capture the effects of viscous friction. A new
      criterion is developed for determining the significance of fluid-fluid
      intermolecular interactions in a nanopore by considering the ratio of oscillation
      times of a fluid molecule in the force field of the surrounding fluid molecules
      and that in the force field of the pore wall. The ratio is shown to give good
      predictions of the region where intermolecular interactions are important and
      explains the region of deviation between theory and simulation in molecularly
      narrow pores.

PMID- 21902274
TI  - Enrichment of humic material with hydroxybenzene moieties intensifies its
      physiological effects on the nematode Caenorhabditis elegans.
AB  - Dissolved humic substances are taken up by organisms and interact on various
      molecular and biochemical levels. In the nematode Caenorhabditis elegans, such
      material can promote longevity and increase its reproductive capacity; moreover,
      the worms tend to stay for longer in humic-enriched environments. Here, we tested
      the hypothesis that the chemical enrichment of humic substances with
      hydroxybenzene moieties intensifies these physiological effects. Based on the
      leonardite humic acid HuminFeed (HF), we followed a polycondensation reaction in
      which this natural humic substance and a dihydroxybenzene (hydroquinone or
      benzoquinone) served as reaction partners. Several analytical methods showed the
      formation of the corresponding copolymers. The chemical modification boosted the
      antioxidant properties of HF both in vitro and in vivo. Humic substances enriched
      with hydroxybenzene moieties caused a significantly increased tolerance to
      thermal stress in C. elegans and extended its lifespan. Exposed nematodes showed
      delayed linear growth and onset of reproduction and a stronger pumping activity
      of the pharynx. Thus, treated nematodes act younger than they really are. In this
      feature the modified HF replicated the biological impact of hydroquinone
      homopolymers and various plant polyphenol monomers, thereby supporting the
      hydroxybenzene moieties of humic substances as major effective structures for the
      physiological effects observed in C. elegans.

PMID- 21902276
TI  - Resolution of discordant HIV-1 protease resistance rankings using molecular
      dynamics simulations.
AB  - The emergence of drug resistance is a major challenge for the effective treatment
      of HIV. In this article, we explore the application of atomistic molecular
      dynamics simulations to quantify the level of resistance of a patient-derived HIV
      1 protease sequence to the inhibitor lopinavir. A comparative drug ranking
      methodology was developed to compare drug resistance rankings produced by the
      Stanford HIVdb, ANRS, and RegaDB clinical decision support systems. The
      methodology was used to identify a patient sequence for which the three rival
      online tools produced differing resistance rankings. Mutations at only three
      positions ( L10I , A71IV, and  L90M ) influenced the resistance level assigned to
      the sequence. We use ensemble molecular dynamics simulations to elucidate the
      origin of these discrepancies and the mechanism of resistance. By simulating not
      only the full patient sequences but also systems containing the constituent
      mutations, we gain insight into why resistance estimates vary and the
      interactions between the various mutations. In the same way, we also gain
      valuable knowledge of the mechanistic causes of resistance. In particular, we
      identify changes in the relative conformation of the two beta sheets that form
      the protease dimer interface which suggest an explanation of the relative
      frequency of different amino acids observed in patients at residue 71.

PMID- 21902275
TI  - Direct functionalization of (un)protected tetrahydroisoquinoline and isochroman
      under iron and copper catalysis: two metals, two mechanisms.
AB  - A highly facile, straightforward synthesis of 1-(3-indolyl)
      tetrahydroisoquinolines was developed using either simple copper or iron
      catalysts. N-protected and unprotected tetrahydroisoquinolines (THIQ) could be
      used as starting materials. Extension of the substrate scope of the
      pronucleophile from indoles to pyrroles and electron-rich arenes was realized.
      Additionally, methoxyphenylation is not limited to THIQ but can be carried out on
      isochroman as well, again employing iron and copper catalysis.

PMID- 21902277
TI  - Dynamic and static behaviors of N-Z-N sigma(3c-4e) (Z = S, Se, and Te)
      interactions: atoms-in-molecules dual functional analysis with high-resolution X
      ray diffraction determination of electron densities for 2-(2-pyridylimino)-2H
      1,2,4-thiadiazolo[2,3-a]pyridine.
AB  - The structure of 2-(2-pyridylimino)-2H-1,2,4-thiadiazolo[2,3-a]pyridine (NSN)
      indicates that the molecule has a planar geometry with a linear N...S...N
      linkage, creating a tetracyclic structure of the formal C(2v) symmetry. To
      clarify the nature of the NSN sigma(3c-4e) bonding, together with the related
      NSeN and NTeN, the dynamic and static behaviors are investigated by applying
      atoms-in-molecules (AIM) dual functional analysis to both the fully optimized and
      perturbed structures. The structures were optimized computationally, retaining
      C(2v) symmetry. All bond critical points are detected as expected and exhibited
      on both sides of the N...Z...N moiety which supports the formation of NZN
      sigma(3c-4e). It is confirmed that N...S...N is of the covalent nature close to
      Me(2)S(+)-*-Cl or Me(2)Se(+)-*-Br, whereas N...Se...N and N...Te...N have the
      (regular) CS nature close to the CT adducts of Me(2)S(-*-Cl)(2) (TBP) and Me(2)Se
      *-Br(2) (MC), respectively. An experimental high-resolution charge density
      determination has been performed on NSN, which thoroughly supports the
      theoretical results. Very similar results are obtained in the analogous pyrimidyl
      derivatives for N...S...N, N...Se...N, and N...Te...N. AIM dual functional
      analysis, as validated by experimental high-resolution charge densities, is thus
      confirmed to be an excellent method to elucidate the nature of these
      interactions.

PMID- 21902278
TI  - REPROVIS-DB: a benchmark system for ligand-based virtual screening derived from
      reproducible prospective applications.
AB  - Benchmark calculations are essential for the evaluation of virtual screening (VS)
      methods. Typically, classes of known active compounds taken from the medicinal
      chemistry literature are divided into reference molecules (search templates) and
      potential hits that are added to background databases assumed to consist of
      compounds not sharing this activity. Then VS calculations are carried out, and
      the recall of known active compounds is determined. However, conventional
      benchmarking is affected by a number of problems that reduce its value for method
      evaluation. In addition to often insufficient statistical validation and the lack
      of generally accepted evaluation standards, the artificial nature of typical
      benchmark settings is often criticized. Retrospective benchmark calculations
      generally overestimate the potential of VS methods and do not scale with their
      performance in prospective applications. In order to provide additional
      opportunities for benchmarking that more closely resemble practical VS
      conditions, we have designed a publicly available compound database (DB) of
      reproducible virtual screens (REPROVIS-DB) that organizes information from
      successful ligand-based VS applications including reference compounds, screening
      databases, compound selection criteria, and experimentally confirmed hits. Using
      the currently available 25 hand-selected compound data sets, one can attempt to
      reproduce successful virtual screens with other than the originally applied
      methods and assess their potential for practical applications.

PMID- 21902279
TI  - Noise-free dual-wavelength difference imaging of plasmonic resonant nanoparticles
      in living cells.
AB  - Herein, we demonstrated a new optical microscopy method to selectively image
      small-size gold nanoparticles (GNPs) inside noisy living cells through
      determination of the difference image between the probe beam (illuminated at the
      resonance wavelength of GNPs, 532 nm) and the reference beam (illuminated at 473
      nm). From computer simulation and single-particle imaging experiments, we
      demonstrated that GNPs with a diameter of 45 nm could be selectively imaged in
      the GNPs/cell lysates mixture and inside living cells by dual-wavelength
      difference (DWD) imaging. The diffusion dynamics of nucleic acids functionalized
      GNPs on cell membranes and the internalization kinetics of these GNPs by living
      cells were explored with this method. Our real-time tracking experiments showed
      that statistically 80% of GNPs were under restricted diffusion on the cell
      membrane. The cell cytoskeleton fence effect, as observed in the single-particle
      tracking experiments, may be one of the main factors for the restricted diffusion
      mode.

PMID- 21902280
TI  - Troubled waters-an examination of the disconnect between river science and law.

PMID- 21902281
TI  - Universal phase transitions of B1-structured stoichiometric transition metal
      carbides.
AB  - The high-pressure phase transitions of B1-structured stoichiometric transition
      metal carbides (TMCs, TM = Ti, Zr, Hf, V, Nb, and Ta) were systematically
      investigated using ab initio calculations. These carbides underwent universal
      phase transitions along two novel phase-transition routes, namely, B1 ->
      distorted TlI (TlI') -> TlI and/or B1 -> distorted TiB (TiB') -> TiB, when
      subjected to pressure. The two routes can coexist possibly because of the tiny
      enthalpy differences between the new phases under corresponding pressures. Four
      new phases result from atomic slips of the B1-structured parent phases under
      pressure. After completely releasing the pressure, taking TiC as representative
      of TMCs, only its new TlI'-type phase is mechanically and dynamically stable, and
      may be recovered.

PMID- 21902282
TI  - Crystal structure of [Al4(OH)6(H2O)12][Al(H2O)6]2Br12: a new polyaluminum
      compound.
AB  - A vertex-shared tetrahedral [Al(4)(OH)(6)(H(2)O)(12)](6+) (Al(4)) and a
      disordered [Al(H(2)O)(6)](3+) (Al(1)) that coexist in a 1:2 ratio within each
      unit cell were observed in the structure of
      [Al(4)(OH)(6)(H(2)O)(12)][Al(H(2)O)(6)](2)Br(12), which crystallized in a cubic
      Fd3m space group from a spontaneously hydrolyzed solution of AlBr(3). The former
      is composed of four AlO(6) octahedra that are connected to each other by sharing
      three vertexes of each octahedron and form a large regular tetrahedron with ideal
      T(d) symmetry. The central Al(3+) ion of the latter is coordinated by 6
      disordered OH(2) molecules, that form a core-shell structure with ideal D(3d)
      symmetry.

PMID- 21902283
TI  - Kinetics of Ga(NOTA) formation from weak Ga-citrate complexes.
AB  - Gallium complexes are gaining increasing importance in biomedical imaging thanks
      to the practical advantages of the (68)Ga isotope in Positron Emission Tomography
      (PET) applications. (68)Ga has a short half-time (t(1/2) = 68 min); thus the
      (68)Ga complexes have to be prepared in a limited time frame. The acceleration of
      the formation reaction of gallium complexes with macrocyclic ligands for
      application in PET imaging represents a significant coordination chemistry
      challenge. Here we report a detailed kinetic study of the formation reaction of
      the highly stable Ga(NOTA) from the weak citrate complex (H(3)NOTA = 1,4,7
      triazacyclononane-1,4,7- triacetic acid). The transmetalation has been studied
      using (71)Ga NMR over a large pH range (pH = 2.01-6.00). The formation of
      Ga(NOTA) is a two-step process. First, a monoprotonated intermediate containing
      coordinated citrate, GaHNOTA(citrate)*, forms in a rapid equilibrium step. The
      rate-determining step of the reaction is the deprotonation and slow rearrangement
      of the intermediate accompanied by the citrate release. The observed reaction
      rate shows an unusual pH dependency with a minimum at pH 5.17. In contrast to the
      typical formation reactions of poly(amino carboxylate) complexes, the Ga(NOTA)
      formation from the weak citrate complex becomes considerably faster with
      increasing proton concentration below pH 5.17. We explain this unexpected
      tendency by the role of protons in the decomposition of the GaHNOTA(citrate)*
      intermediate which proceeds via the protonation of the coordinated citrate ion
      and its subsequent decoordination to yield the final product Ga(NOTA). The
      stability constant of this intermediate, log K(GaHNOTA(citrate)*) = 15.6, is
      remarkably high compared to the corresponding values reported for the formation
      of macrocyclic lanthanide(III)-poly(amino carboxylates). These kinetic data do
      not only give mechanistic insight into the formation reaction of Ga(NOTA), but
      might also contribute to establish optimal experimental conditions for the rapid
      preparation of Ga(NOTA)-based radiopharmaceuticals for PET applications.

PMID- 21902284
TI  - Fusion of lipid vesicles with planar lipid bilayers induced by a combination of
      peptides.
AB  - We studied the peptide-induced membrane fusion process between small unilamellar
      vesicles (SUVs) and supported planar bilayers (SPBs) with the aim of developing a
      method for incorporating membrane components into SPBs. As fusogenic peptides,
      two analogues of the N-terminal region of an influenza membrane fusion protein
      hemaggulutinin, anionic E5 and cationic K5, were synthesized, and the membrane
      fusion was investigated using SPB and SUVs composed of phosphatidylcholine from
      egg yolk (EggPC). We directly visualized the process of lipid transfer from SUVs
      to SPB by total internal reflection fluorescence (TIRF) microscopy. The transfer
      of fluorescent lipids was effectively induced only by the combination of two
      peptides. The TIRF microscopy observations of single SUV fusion events also
      revealed that lipid membranes from SUV could completely fuse into the SPB.
      However, the presence of single peptide (either E5 or K5) rather inhibited the
      lipid transfer, presumably due to the electrostatic repulsion between SUVs and
      SPB. The opposite effects induced by the peptides indicate the possibility for a
      designed application of two peptides as a means to control the membrane fusion
      spatially and temporally.

PMID- 21902285
TI  - Impact of respiratory syncytial virus: the nurse's perspective.
AB  - Respiratory syncytial virus (RSV) is a highly contagious virus, and is the major
      cause of lower respiratory tract infections in infants and toddlers worldwide.
      RSV infection poses serious health risks to young children during the first 2
      years of life. Several infant populations have been classified as high risk, and
      additional risk factors are known to increase the likelihood of severe RSV
      infection. Treatment for active RSV infection is limited to the symptoms of
      infection rather than the underlying cause; therefore, it is critical to reduce
      the transmission of RSV. As nurses, we highlight the importance of educating
      healthcare professionals, both in the hospital and community settings, as well as
      parents and other caregivers about the risks and outcomes associated with RSV
      infection, and necessary measures to decrease the risk of infection. We also
      highlight the importance of the successful identification of those children who
      are at high risk of RSV infection. RSV prophylaxis (RSVP) with palivizumab has
      been shown to improve clinical outcome in infants who are considered high risk
      compared with those who have not received RSVP. The failure of healthcare staff
      and primary caregivers to protect children against an RSV infection can have
      lasting detrimental effects on the health and lives of affected children and
      their families.

PMID- 21902287
TI  - Impact of intravenous naltrexone on intravenous morphine-induced high, drug
      liking, and euphoric effects in experienced, nondependent male opioid users.
AB  - BACKGROUND: Opioid analgesics can be abused by crushing followed by
      solubilization and intravenous injection to attain rapid absorption. Morphine
      sulfate and naltrexone hydrochloride extended release capsules (EMBEDA, MS-sNT),
      indicated for management of chronic, moderate to severe pain, contain pellets of
      morphine sulfate with a sequestered naltrexone core. Should product tampering by
      crushing occur, the sequestered naltrexone is intended for release to reduce
      morphine-induced subjective effects. OBJECTIVE: This study compared self-reports
      of high, euphoria, and drug-liking effects of intravenous morphine alone versus
      intravenous morphine combined with naltrexone in a clinical simulation of
      intravenous abuse of crushed MS-sNT. METHODS: This single-center, randomized,
      double-blind, crossover study characterized subjective effects of naltrexone
      administered intravenously at the same ratio to morphine present in MS-sNT.
      Subjects were male and had used prescription opioids five or more times within
      the previous 12 months to get 'high' but were not physically dependent on
      opioids. The primary outcome was the response to the Drug Effects Questionnaire
      (DEQ) question #5, "How high are you now?" (100 mm Visual Analog Scale [VAS]).
      The secondary outcome was the response to a Cole/Addiction Research Center
      Inventory (ARCI) Stimulation-Euphoria modified scale. Additional outcomes
      included response to VAS drug liking, the remaining DEQ questions, and
      pupillometry. RESULTS: Administration of intravenous naltrexone following
      intravenous morphine diminished mean high (29.8 vs 85.2 mm), Cole/ARCI
      Stimulation-Euphoria (13.7 vs 27.8 mm), and drug-liking (38.9 vs 81.4 mm) scores
      (all p < 0.0001) compared with intravenous morphine alone. No serious adverse
      events occurred as a result of the tested ratio of naltrexone to morphine.
      CONCLUSIONS: Results in this study population suggest that naltrexone added to
      morphine in the 4% ratio within MS-sNT mitigates the high, euphoria, and drug
      liking of morphine alone, potentially reducing the attractiveness for product
      tampering. Assessment of the true clinical significance of these findings will
      require further study.

PMID- 21902288
TI  - Short-term acetylsalicylic acid (aspirin) use for pain, fever, or colds -
      gastrointestinal adverse effects: a meta-analysis of randomized clinical trials.
AB  - BACKGROUND AND AIM: Acetylsalicylic acid (ASA [aspirin]) is a commonly used over
      the-counter drug for the treatment of pain, fever, or colds, but data on the
      safety of this use are very limited. The aim of this study was to provide data on
      the safety of this treatment pattern, which is of interest to clinicians,
      regulators, and the public. METHODS: A meta-analysis of individual patient data
      from 67 studies sponsored by Bayer HealthCare was completed. The primary
      endpoints were patient-reported gastrointestinal (GI) adverse events (AEs); the
      secondary endpoints were the incidence of patient-reported non-GI AEs. Event
      incidence and odds ratios (ORs) based on Cochran-Mantel-Haenszel estimates are
      reported. In total, 6181 patients were treated with ASA, 3515 with placebo, 1145
      with acetaminophen (paracetamol), and 754 with ibuprofen. Exposure to ASA was
      short term (82.5% of patients had a single dose). RESULTS: GI AEs were more
      frequent with ASA (9.9%) than with placebo (9.0%).[OR 1.3; 95% CI 1.1, 1.5].
      Dyspeptic symptoms were infrequent (4.6% in placebo subjects). The ORs for ASA
      were 1.3 (95% CI 1.1, 1.6) versus placebo; 1.55 (95% CI 0.7, 3.3) versus
      ibuprofen; and 1.04 (95% CI 0.8, 1.4) versus acetaminophen. There were very few
      serious GI AEs (one ASA case; three placebo cases). No differences were found for
      non-GI AEs and no cases of cerebral hemorrhage were reported. CONCLUSION: Short
      term, mostly single-dose exposure to ASA for the treatment of pain, fever, or
      colds was associated with a small but significant increase in the risk of
      dyspepsia relative to placebo. No serious GI complications were reported.

PMID- 21902289
TI  - Tissue-selective estrogen complex bazedoxifene and conjugated estrogens for the
      treatment of menopausal vasomotor symptoms.
AB  - Menopause occurs on average at age 51.4 years. Most, but not all, women who
      undergo menopause experience significant vasomotor symptoms (VMS). Although
      single agent estrogen therapy can relieve VMS, over time estrogen can stimulate
      the endometrial lining leading to an increased risk for endometrial hyperplasia
      and adenocarcinoma. Although a progestin has traditionally been given in
      combination with estrogen to 'protect' the endometrium, a new and innovative
      approach to this traditional combination hormone therapy is to substitute the
      progestin with an alternative agent. One such alternative agent is bazedoxifene,
      an estrogen agonist-antagonist. Based on data from randomized trials, when
      bazedoxifene is given in combination with oral conjugated estrogens to post
      menopausal women, the risk of estrogen-associated endometrial stimulation is
      significantly reduced. The combination of bazedoxifene and conjugated estrogens
      has also been shown to relieve menopause-associated VMS and vaginal atrophy, and
      has been shown to be safe for short-term use. Long-term studies of this
      combination are needed to determine if the combination of conjugated
      estrogens/bazedoxifene can be used for >3 years without increasing the risk of
      breast cancer, stroke, cognitive deficit, pulmonary embolism or coronary heart
      disease. Short-term data regarding this combination has been submitted to the FDA
      and is currently under review for clinical use, with the relief of VMS as its
      primary indication. Data regarding the effects of combination conjugated
      estrogens/bazedoxifene therapy on bone are promising in terms of the prevention
      and treatment of post-menopausal osteoporosis.

PMID- 21902286
TI  - Clinical and experimental applications of sodium phenylbutyrate.
AB  - Histone acetyltransferase and histone deacetylase are enzymes responsible for
      histone acetylation and deacetylation, respectively, in which the histones are
      acetylated and deacetylated on lysine residues in the N-terminal tail and on the
      surface of the nucleosome core. These processes are considered the most important
      epigenetic mechanisms for remodeling the chromatin structure and controlling the
      gene expression. Histone acetylation is associated with gene activation. Sodium
      phenylbutyrate is a histone deacetylase inhibitor that has been approved for
      treatement of urea cycle disorders and is under investigation in cancer,
      hemoglobinopathies, motor neuron diseases, and cystic fibrosis clinical trials.
      Due to its characteristics, not only of histone deacetylase inhibitor, but also
      of ammonia sink and chemical chaperone, the interest towards this molecule is
      growing worldwide. This review aims to update the current literature, involving
      the use of sodium phenylbutyrate in experimental studies and clinical trials.

PMID- 21902290
TI  - Vaccination strategies in lymphomas and leukaemias: recent progress.
AB  - The successful identification of a range of leukaemia-specific and lymphoma
      specific antigens in recent years has stimulated efforts to develop therapeutic
      vaccination strategies. A number of clinical trials have established the safety
      and immunogenicity of vaccination against tumour antigens, although there are
      limited data on the clinical efficacy of this approach in haematological
      malignancies. After encouraging results of phase I/II trials using idiotype
      vaccines in lymphoma, the outcome of the three phase III trials has been somewhat
      disappointing. Several other promising strategies are currently being developed
      to improve these results, including optimization of antigen delivery. In myeloid
      leukaemias, clinical trials of vaccination with peptides derived from a number of
      leukaemia antigens, including WT1, PR1, RHAMM and BCR-ABL, have shown evidence of
      immunogenicity, but limited data are available on the clinical efficacy of this
      approach. In this review, we focus on the results of clinical trials of
      vaccination in leukaemia and lymphoma, and discuss potential strategies to
      enhance the efficacy of immunotherapy in the future.

PMID- 21902291
TI  - Glucagon-like peptide-1 analogues for Type 2 diabetes mellitus: current and
      emerging agents.
AB  - Novel therapeutic options for type 2 diabetes mellitus based on the action of the
      incretin hormone glucagon-like peptide (GLP)-1 were introduced in 2005. As
      injectable GLP-1 receptor agonists acting on the GLP-1 receptor, exenatide and
      liraglutide are available in many countries. In type 2 diabetes treatment,
      incretin-based therapies are attractive and more commonly used because of their
      mechanism of action and safety profile. Stimulation of insulin secretion and
      inhibition of glucagon secretion by these agents occur in a glucose-dependent
      manner. Therefore, incretin-based therapies have no intrinsic risk for
      hypoglycaemia. Furthermore, GLP-1 receptor agonists allow weight loss and lower
      systolic blood pressure. This review gives a brief overview of the mechanism of
      action and summarizes the clinical data available on exenatide and liraglutide as
      established substances. It further highlights the clinical study data of
      exenatide once weekly as the first long-acting GLP-1 receptor agonist and covers
      other new long acting GLP-1 receptor agonists currently in clinical development.
      The placement of GLP-1 receptor agonists in the treatment algorithm of type 2
      diabetes is discussed.

PMID- 21902292
TI  - Pharmacological modulation of arterial stiffness.
AB  - Arterial stiffness has emerged as an important marker of cardiovascular risk in
      various populations and reflects the cumulative effect of cardiovascular risk
      factors on large arteries, which in turn is modulated by genetic background.
      Arterial stiffness is determined by the composition of the arterial wall and the
      arrangement of these components, and can be studied in humans non-invasively. Age
      and distending pressure are two major factors influencing large artery stiffness.
      Change in arterial stiffness with drugs is an important endpoint in clinical
      trials, although evidence for arterial stiffness as a therapeutic target still
      needs to be confirmed. Drugs that independently affect arterial stiffness include
      antihypertensive drugs, mostly blockers of the renin-angiotensin-aldosterone
      system, hormone replacement therapy and some antidiabetic drugs such as
      glitazones. While the quest continues for 'de-stiffening drugs', so far only
      advanced glycation endproduct cross-link breakers have shown promise.

PMID- 21902295
TI  - Pirfenidone: in idiopathic pulmonary fibrosis.
AB  - Pirfenidone is an orally administered pyridine that has orphan designation for
      the treatment of mild to moderate idiopathic pulmonary fibrosis (IPF) in the EU.
      Pirfenidone 2403 mg/day for 72 weeks administered to patients with IPF was
      associated with a significantly lower mean decline in the percent predicted
      forced vital capacity than placebo (primary endpoint) according to data from one
      of two randomized, double-blind, multinational trials (studies 004 and 006 [also
      known as the CAPACITY trials]), and data from a pooled analysis of both trials.
      In another randomized, double-blind, multicentre Japanese trial, the adjusted
      mean in the change in vital capacity from baseline to week 52 was significantly
      lower in patients with IPF who received pirfenidone 1800 mg/day (considered to be
      comparable to the 2403 mg/day dose in studies 004 and 006 on a weight-normalized
      basis) than in those who received placebo (primary endpoint). Pirfenidone had an
      acceptable tolerability profile in clinical trials, with most adverse events
      being mild to moderate in severity.

PMID- 21902293
TI  - Triple antiplatelet therapy in acute coronary syndromes.
AB  - Heightened platelet activity plays a critical role in thrombus formation, which
      is central to acute coronary syndromes (ACS), including non-ST-segment elevation
      (NSTE)-ACS (comprising unstable angina pectoris and non-ST-segment elevation
      myocardial infarction [NSTEMI]) and ST-segment elevation myocardial infarction
      (STEMI), and has been implicated in poor clinical outcome. Platelets not only
      impact coronary thrombus but are major contributors to microcirculatory
      dysfunction and vascular inflammation. Efforts to inhibit platelet function,
      including antiplatelet therapy, are paramount to the management of ACS; thus, a
      growing recognition of the various pathways driving platelet activity has given
      rise to the need for multiple agents that impart complimentary mechanisms of
      action. While only inhibiting platelet activation will still allow for
      aggregation, i.e. the binding of glycoprotein (GP) IIb/IIIa receptors to
      fibrinogen, solely blocking aggregation may leave platelet-activating pathways
      free to sustain the production and release of various pro-inflammatory and pro
      thrombotic compounds. The benefit of 'triple antiplatelet therapy', referring to
      the combination of aspirin, a thienopyridine or non-thienopyridine adenosine
      diphosphate (ADP)/P2Y12 receptor blocker and a GPIIb/IIIa inhibitor (GPI), has
      been demonstrated in patients with NSTE-ACS who ultimately undergo percutaneous
      coronary intervention (PCI) and are determined to be at an elevated risk for
      ischaemic events, and in patients undergoing primary PCI. It is therefore
      recommended by the European Society of Cardiology (ESC) and American College of
      Cardiology/American Heart Association. Furthermore, the rationale for adding a
      GPI, particularly in patients with STEMI, is backed by studies that have shown
      negligible effects of a 600 mg clopidogrel loading dose, despite being
      administered 4 hours prior to PCI. Moreover, it has been observed that the
      physiological state of STEMI may deem dual antiplatelet therapy ineffective,
      because during an acute event the absorption of clopidogrel may be impaired.
      Nonetheless, there is still considerable variability with respect to the use of
      triple antiplatelet therapy such as that documented in the Euro Heart Survey. The
      perception that the mortality benefit afforded by adding a GPI to dual oral
      antiplatelet therapy does not outweigh the risk is a likely factor. This may be
      fuelled by results of trials such as BRAVE-3, which, inconsistent with those for
      On-TIME 2, failed to prove the value of adding a GPI to dual oral antiplatelet
      therapy in patients with STEMI. Subsequent analyses have indeed demonstrated the
      positive benefit-risk ratio associated with adding a GPI and determined that the
      timing of GPI administration could have an impact on clinical outcome related to
      its impact on infarct size in patients with STEMI. Additionally, it has been
      presumed that a synergistic effect exists between P2Y12 inhibitors and GPIs.
      Triple antiplatelet therapy has a significant role to play in the management of
      patients with ACS managed with PCI. An understanding of patient risk status and
      timing of symptoms and bleeding risk is crucial to patient selection and ensuring
      that this therapy is optimized. Though no interaction has been noted in trials of
      newer, more potent antiplatelet agents, future studies are key to determining the
      role of this strategy in the era of these more potent agents.

PMID- 21902296
TI  - Ustekinumab: a review of its use in the management of moderate to severe plaque
      psoriasis.
AB  - Ustekinumab (StelaraTM) is a human monoclonal antibody that binds to the p40
      subunit common to both interleukin (IL)-12 and IL-23. It is indicated in the US
      for use in adult patients with moderate to severe plaque psoriasis who are
      candidates for phototherapy or systemic therapy. In the EU, it is indicated for
      those who failed to respond to, have a contraindication to or are intolerant of
      other systemic therapies or phototherapy. This article reviews the efficacy and
      tolerability of ustekinumab in patients with moderate to severe plaque psoriasis,
      as well as summarizing its pharmacological properties. Ustekinumab attenuates the
      immune cell activation properties of IL-12 and IL-23. It interrupts the abnormal
      activation of signalling and cytokine cascades that underlie the pathology of
      psoriasis by reducing the expression of IL-12- and IL-23-induced cell surface
      markers that mediate skin homing, activation and cytokine release. In well
      designed, randomized clinical trials, regimens of subcutaneous ustekinumab 45 or
      90 mg provided a rapid and durable improvement in psoriasis area severity index
      (PASI) scores for patients with moderate to severe plaque psoriasis. A
      significantly greater proportion of patients receiving ustekinuman 45 or 90 mg
      compared with those receiving placebo achieved a >=75% improvement from baseline
      in PASI score following 12 weeks' treatment (primary endpoint). Improvements in
      PASI scores were evident following 2 weeks' treatment with ustekinumab and were
      sustained for up to 3 years. Treatment with ustekinumab 45 or 90 mg also improved
      health-related quality-of-life scores from baseline. Following 12 weeks'
      treatment, ustekinumab 45 or 90 mg was more effective than etanercept 50 mg twice
      weekly in providing symptomatic relief for patients with moderate to severe
      plaque psoriasis. Furthermore, ustekinumab treatment provided effective
      symptomatic improvement for almost half of the patients who showed no response to
      12 weeks' treatment with etanercept. More limited data indicate that ustekinumab
      also improves the symptoms of arthritis in patients with plaque psoriasis and
      psoriatic arthritis. Subcutaneous ustekinumab was generally well tolerated in
      clinical trials; most adverse events were mild in intensity and did not require
      dosage adjustment. A pooled analysis of clinical trial data indicated no specific
      patterns of infection for recipients of ustekinumab and that infection rates
      remained stable following cumulative exposure to the agent. In conclusion,
      subcutaneous ustekinumab provides an effective and well tolerated alternative for
      the symptomatic treatment of patients with moderate to severe plaque psoriasis.

PMID- 21902297
TI  - Eldecalcitol: a review of its use in the treatment of osteoporosis.
AB  - Eldecalcitol (1alpha,25[OH](2)-2beta-(3-hydroxypropyloxy)vitamin D(3); ED-71;
      Edirol(r)) is an orally administered analogue of active vitamin D (calcitriol)
      that is available in Japan for the treatment of osteoporosis. Two randomized,
      double-blind, multicentre trials were conducted in patients with osteoporosis. In
      a placebo-controlled, dose-ranging trial, eldecalcitol significantly reduced
      serum bone-specific alkaline phosphatase (BALP) and serum osteocalcin, markers of
      bone formation, more than placebo. Eldecalcitol at a 1.0 MUg/day dosage, but not
      at lower dosages, also significantly reduced urinary type I collagen N
      telopeptide (NTX), a marker of bone resorption, more than placebo. In a
      comparison with alfacalcidol (a prodrug of calcitriol), eldecalcitol produced
      significantly greater reductions in serum BALP and urinary NTX, and had a
      positive effect on CT markers of femoral biomechanical properties. In the
      comparison with alfacalcidol, eldecalcitol 0.75 MUg/day significantly reduced the
      3-year incidence of vertebral fractures, with an absolute risk reduction of 4.1%
      over this period, representing a relative risk reduction of 26%. There was no
      significant difference in the rate of non-vertebral fractures. In both trials,
      eldecalcitol treatment was also associated with an increase in bone mineral
      density, whereas patients who received the comparators generally had a reduction
      in bone mineral density. Increases in blood calcium (to >2.6 mmol/L) and urinary
      calcium (to >0.1 mmol/L glomerular filtrate) were the most clinically important
      treatment-emergent adverse events. In the placebo-controlled, dose-ranging trial,
      23% and 25% of patients in the eldecalcitol 1 MUg/day group had increased blood
      and urinary calcium compared with 7% and 7%, 6% [corrected] and 9%, and 0% and
      1.9% in the eldecalcitol 0.5 and 0.75 MUg/day, and placebo groups, respectively.
      In the comparison with alfacalcidol, 21.0% and 13.5% of eldecalcitol 0.75 MUg/day
      and alfacalcidol 1.0 MUg/day recipients had increased blood calcium, whereas
      hypercalcaemia (defined as a serum calcium >2.9 mmol/L) occurred in 0.4% and
      urolithiasis in 1.3% of eldecalcitol recipients over 36 months of treatment.
      Eldecalcitol is an efficacious treatment for patients with osteoporosis that
      should be further investigated in head-to-head trials with other recommended
      first-line pharmacological treatments.

PMID- 21902299
TI  - Crossover from adiabatic to antiadiabatic quantum pumping with dissipation.
AB  - Quantum pumping, in its different forms, is attracting attention from different
      fields, from fundamental quantum mechanics, to nanotechnology, to
      superconductivity. We investigate the crossover of quantum pumping from the
      adiabatic to the antiadiabatic regime in the presence of dissipation, and find
      general and explicit analytical expressions for the pumped current in a minimal
      model describing a system with the topology of a ring forced by a periodic
      modulation of frequency omega. The solution allows following in a transparent way
      the evolution of pumped dc current from much smaller to much larger omega values
      than the other relevant energy scale, the energy splitting introduced by the
      modulation. We find and characterize a temperature-dependent optimal value of the
      frequency for which the pumped current is maximal.

PMID- 21902300
TI  - Rydberg excitations in Bose-Einstein condensates in quasi-one-dimensional
      potentials and optical lattices.
AB  - We experimentally realize Rydberg excitations in Bose-Einstein condensates of
      rubidium atoms loaded into quasi-one-dimensional traps and in optical lattices.
      Our results for condensates expanded to different sizes in the one-dimensional
      trap agree well with the intuitive picture of a chain of Rydberg excitations. We
      also find that the Rydberg excitations in the optical lattice do not destroy the
      phase coherence of the condensate, and our results in that system agree with the
      picture of localized collective Rydberg excitations including nearest-neighbor
      blockade.

PMID- 21902298
TI  - Dasatinib: a review of its use in the treatment of chronic myeloid leukaemia and
      Philadelphia chromosome-positive acute lymphoblastic leukaemia.
AB  - Dasatinib (Sprycel(r)) is an orally administered small molecule inhibitor of
      multiple tyrosine kinases, including BCR-ABL and SRC family kinases, which is
      indicated for the treatment of adults with newly diagnosed chronic-phase chronic
      myeloid leukaemia (CML), CML (chronic-, accelerated- or blast-phase) with
      resistance or intolerance to prior therapy, including imatinib, or Philadelphia
      chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) with resistance or
      intolerance to prior therapy. Dasatinib is ~325-fold more active than imatinib in
      inhibiting wild-type ABL kinase in vitro and is active against a wide variety of
      imatinib-resistant BCR-ABL mutants, except for T315I. This article reviews the
      efficacy and tolerability of dasatinib in the treatment of patients with newly
      diagnosed chronic-phase CML or imatinib-resistant or -intolerant CML or Ph+ ALL,
      as well as summarizing its pharmacological properties. In clinical trials, oral
      dasatinib was effective in achieving major or complete cytogenetic responses in
      both newly diagnosed and imatinib-resistant or -intolerant chronic-phase CML.
      Dasatinib was likewise effective in achieving major or overall haematological
      responses in imatinib-resistant or -intolerant, accelerated- or blast-phase CML,
      or Ph+ ALL. Responses were rapidly achieved within 1-3 months and were durable
      over 1-5 years of follow-up. The majority of adverse events with dasatinib were
      of mild to moderate severity. Fluid retention (including pleural effusion) was
      the most common adverse event. Haematological abnormalities were common and
      cytopenias were the most common grade 3/4 adverse events. Dasatinib 100 mg
      administered once daily was as effective as dasatinib 70 mg administered twice
      daily, and was better tolerated, being associated with lower incidences of
      pleural effusion and grade 3/4 thrombocytopenia, in particular. Dasatinib was
      more effective than high-dose imatinib in the treatment of patients with imatinib
      resistant chronic-phase CML and was more effective than standard dosages of
      imatinib, as well as being associated with less frequent fluid retention, in
      patients with newly diagnosed chronic-phase CML. Dasatinib was generally equally
      effective in patients with or without BCR-ABL mutations at baseline. Therefore,
      oral dasatinib is a highly effective once-daily therapy for the first-line
      treatment of newly diagnosed patients with chronic-phase CML, as well as for the
      treatment of patients with imatinib-resistant or -intolerant chronic- and
      advanced-phase CML or Ph+ ALL.

PMID- 21902301
TI  - Nonequilibrium phase transition in a periodically driven XY spin chain.
AB  - We present a general formulation of Floquet states of periodically time-dependent
      open Markovian quasifree fermionic many-body systems in terms of a discrete
      Lyapunov equation. Illustrating the technique, we analyze periodically kicked XY
      spin-1/2 chain which is coupled to a pair of Lindblad reservoirs at its ends. A
      complex phase diagram is reported with reentrant phases of long range and
      exponentially decaying spin-spin correlations as some of the system's parameters
      are varied. The structure of phase diagram is reproduced in terms of counting
      nontrivial stationary points of Floquet quasiparticle dispersion relation.

PMID- 21902302
TI  - Limit of spin squeezing in finite-temperature Bose-Einstein condensates.
AB  - We show that, at finite temperature, the maximum spin squeezing achievable using
      interactions in Bose-Einstein condensates has a finite limit when the atom number
      N->infinity at fixed density and interaction strength. We calculate the limit of
      the squeezing parameter for a spatially homogeneous system and show that it is
      bounded from above by the initial noncondensed fraction.

PMID- 21902303
TI  - Local realism of macroscopic correlations.
AB  - We identify conditions under which correlations resulting from quantum
      measurements performed on macroscopic systems (systems composed of a number of
      particles of the order of the Avogadro number) can be described by local realism.
      We argue that the emergence of local realism at the macroscopic level is caused
      by an interplay between the monogamous nature of quantum correlations and the
      fact that macroscopic measurements do not reveal properties of individual
      particles.

PMID- 21902304
TI  - Two-dimensional Rydberg gases and the quantum hard-squares model.
AB  - We study a two-dimensional lattice gas of atoms that are photoexcited to Rydberg
      states in which they interact via the van der Waals interaction. We explore the
      regime of dominant nearest-neighbor interaction where this system is intimately
      connected with a quantum version of Baxter's hard-squares model. We show that the
      strongly correlated ground state of the Rydberg gas can be analytically described
      by a projected entangled pair state that constitutes the ground state of the
      quantum hard-squares model. This correspondence allows us to identify a phase
      boundary where the Rydberg gas undergoes a transition from a disordered (liquid)
      phase to an ordered (solid) phase.

PMID- 21902305
TI  - Thermal states as universal resources for quantum computation with always-on
      interactions.
AB  - Measurement-based quantum computation utilizes an initial entangled resource
      state and proceeds with subsequent single-qubit measurements. It is implicitly
      assumed that the interactions between qubits can be switched off so that the
      dynamics of the measured qubits do not affect the computation. By proposing a
      model spin Hamiltonian, we demonstrate that measurement-based quantum computation
      can be achieved on a thermal state with always-on interactions. Moreover,
      computational errors induced by thermal fluctuations can be corrected and thus
      the computation can be executed fault tolerantly if the temperature is below a
      threshold value.

PMID- 21902306
TI  - Cavity QED with magnetically coupled collective spin states.
AB  - We report strong coupling between an ensemble of nitrogen-vacancy center electron
      spins in diamond and a superconducting microwave coplanar waveguide resonator.
      The characteristic scaling of the collective coupling strength with the square
      root of the number of emitters is observed directly. Additionally, we measure
      hyperfine coupling to (13)C nuclear spins, which is a first step towards a
      nuclear ensemble quantum memory. Using the dispersive shift of the cavity
      resonance frequency, we measure the relaxation time of the NV center at
      millikelvin temperatures in a nondestructive way.

PMID- 21902307
TI  - Improving free-energy estimates from unidirectional work measurements: theory and
      experiment.
AB  - We derive analytical expressions for the bias of the Jarzynski free-energy
      estimator from N nonequilibrium work measurements, for a generic work
      distribution. To achieve this, we map the estimator onto the random energy model
      in a suitable scaling limit parametrized by (logN)/MU, where MU measures the
      width of the lower tail of the work distribution, and then compute the finite-N
      corrections to this limit with different approaches for different regimes of
      (logN)/MU. We show that these expressions describe accurately the bias for a wide
      class of work distributions and exploit them to build an improved free-energy
      estimator from unidirectional work measurements. We apply the method to optical
      tweezers unfolding and refolding experiments on DNA hairpins of varying loop size
      and dissipation, displaying both near-Gaussian and non-Gaussian work
      distributions.

PMID- 21902308
TI  - Coherent Cherenkov radiation from cosmic-ray-induced air showers.
AB  - Very energetic cosmic rays entering the atmosphere of Earth will create a plasma
      cloud moving with almost the speed of light. The magnetic field of Earth induces
      an electric current in this cloud which is responsible for the emission of
      coherent electromagnetic radiation. We propose to search for a new effect:
      Because of the index of refraction of air, this radiation is collimated in a
      Cherenkov cone. To express the difference from usual Cherenkov radiation, i.e.,
      the emission from a fast-moving electric charge, we call this magnetically
      induced Cherenkov radiation. We indicate its signature and possible experimental
      verification.

PMID- 21902309
TI  - Quantum theory of fermion production after inflation.
AB  - We show that quantum effects dramatically enhance the production of fermions
      following preheating after inflation in the early Universe in the presence of
      high excitations of bosonic quanta. As a consequence, fermions rapidly approach a
      quasistationary distribution with a thermal occupancy in the infrared, while the
      inflaton enters a turbulent scaling regime. The failure of standard semiclassical
      descriptions based on the Dirac equation with a homogeneous background field is
      caused by nonperturbatively high boson occupation numbers. During preheating the
      inflaton occupation number increases, thus leading to a dynamical mechanism for
      the enhanced production of fermions from the rescattering of the inflaton quanta.
      We comment on related phenomena in heavy-ion collisions for the production of
      quark matter fields from highly occupied gauge bosons.

PMID- 21902311
TI  - General method for determining the masses of semi-invisibly decaying particles at
      hadron colliders.
AB  - We present a general solution to the long-standing problem of determining the
      masses of pair-produced, semi-invisibly decaying particles at hadron colliders.
      We define two new transverse kinematic variables M(CT)(?) and M(CT)(?), which are
      suitable one-dimensional projections of the contransverse mass M(CT). We derive
      analytical formulas for the boundaries of the kinematically allowed regions in
      the (M(CT)(?),M(CT)(?)) and (M(CT)(?),M(CT)) parameter planes and introduce
      suitable variables D(CT)(?) and D(CT) to measure the distance to those boundaries
      on an event per event basis. We show that the masses can be reliably extracted
      from the end-point measurements of M(CT)(?)(max) and D(CT)(min) (or
      D(CT)(?)(min)). We illustrate our method with dilepton tt events at the LHC.

PMID- 21902310
TI  - Pseudo-Goldstino in field theory.
AB  - We consider two SUSY-breaking hidden sectors which decouple when their respective
      couplings to the visible particles are switched off. In such a scenario one
      expects to find two light fermions: the Goldstino and the pseudo-Goldstino. While
      the former remains massless in the rigid limit, the latter becomes massive due to
      radiative effects which we analyze from several different points of view. This
      analysis is greatly facilitated by a version of the Goldberger-Treiman relation,
      which allows us to write a universal nonperturbative formula for the mass. We
      carry out the analysis in detail in the context of gauge mediation, where we find
      that the pseudo-Goldstino mass is at least around the GeV scale and can be easily
      at the electroweak range, even in low scale models. This leads to interesting and
      unconventional possibilities in collider physics and it also has potential
      applications in cosmology.

PMID- 21902312
TI  - Top quark asymmetry and Wjj excess at CDF from gauged flavor symmetry.
AB  - We show that the scalar sector needed for fermion mass generation when the flavor
      symmetry of the standard model is maximally gauged can consistently explain two
      anomalies reported recently by the CDF Collaboration-the forward-backward
      asymmetry in tt pair production and the dijet invariant mass in the Wjj channel.
      A pair of nearly degenerate scalar doublets with masses in the range 150-200 GeV
      explain these anomalies, with additional scalars predicted in the mass range 100
      400 GeV. Consistency of such low scale flavor physics with flavor-changing
      processes is shown, and expectations for the LHC are outlined.

PMID- 21902313
TI  - Nonzero theta13 for neutrino mixing in the context of A4 symmetry.
AB  - In the original 2004 paper which first derived tribimaximal mixing in the context
      of A(4), i.e., the non-Abelian finite symmetry group of the tetrahedron, as its
      simplest application, it was also pointed out how theta(13) ? 0 may be
      accommodated. On the strength of the new T2K result that 0.03(0.04) <=
      sin(2)2theta(13) <= 0.28(0.34) for delta(CP) = 0 and normal (inverted) neutrino
      mass hierarchy, we perform a more detailed analysis of how this original idea may
      be realized in the context of A(4).

PMID- 21902314
TI  - Probing gluonic spin-orbit correlations in photon pair production.
AB  - We consider photon pair production in hadronic collisions at large mass and small
      transverse momentum of the pair, assuming that factorization in terms of
      transverse-momentum dependent parton distributions applies. The unpolarized cross
      section is found to have azimuthal angular dependencies that are generated by a
      gluonic version of the Boer-Mulders function. In addition, the single
      transversely polarized cross section is sensitive to the gluon Sivers function.
      We present simple numerical estimates for the Boer-Mulders and Sivers effects in
      diphoton production at RHIC and find that the process would offer unique
      opportunities for exploring transverse-momentum dependent gluon distributions.

PMID- 21902315
TI  - Chiral two-body currents in nuclei: Gamow-Teller transitions and neutrinoless
      double-beta decay.
AB  - We show that chiral effective field theory (EFT) two-body currents provide
      important contributions to the quenching of low-momentum-transfer Gamow-Teller
      transitions, and use chiral EFT to predict the momentum-transfer dependence that
      is probed in neutrinoless double-beta (0nubetabeta) decay. We then calculate for
      the first time the 0nubetabeta decay operator based on chiral EFT currents and
      study the nuclear matrix elements at successive orders. The contributions from
      chiral two-body currents are significant and should be included in all
      calculations.

PMID- 21902316
TI  - Complete electric dipole response and the neutron skin in 208Pb.
AB  - A benchmark experiment on (208)Pb shows that polarized proton inelastic
      scattering at very forward angles including 0 degrees  is a powerful tool for
      high-resolution studies of electric dipole (E1) and spin magnetic dipole (M1)
      modes in nuclei over a broad excitation energy range to test up-to-date nuclear
      models. The extracted E1 polarizability leads to a neutron skin thickness r(skin)
      = 0.156(-0.021)(+0.025) fm in (208)Pb derived within a mean-field model [Phys.
      Rev. C 81, 051303 (2010)], thereby constraining the symmetry energy and its
      density dependence relevant to the description of neutron stars.

PMID- 21902317
TI  - Heavy-particle radioactivity of superheavy nuclei.
AB  - The concept of heavy-particle radioactivity (HPR) is changed to allow emitted
      particles with Z(e) > 28 from parents with Z > 110 and daughter around (208)Pb.
      Calculations for superheavy (SH) nuclei with Z = 104-124 are showing a trend
      toward shorter half-lives and larger branching ratio relative to alpha decay for
      heavier SHs. It is possible to find regions in which HPR is stronger than alpha
      decay. The new mass table AME11 and the theoretical KTUY05 and FRDM95 masses are
      used to determine the released energy. For 124 we found isotopes with half-lives
      in the range of ns to ps.

PMID- 21902318
TI  - Measurement of the betabeta decay half-life of 130Te with the NEMO-3 detector.
AB  - We report results from the NEMO-3 experiment based on an exposure of 1275 days
      with 661 g of (130)Te in the form of enriched and natural tellurium foils. The
      betabeta decay rate of (130)Te is found to be greater than zero with a
      significance of 7.7 standard deviations and the half-life is measured to be
      T(1/2)(2nu) = [7.0 +/- 0.9(stat) +/- 1.1(syst)] * 10(20) yr. This represents the
      most precise measurement of this half-life yet published and the first real-time
      observation of this decay.

PMID- 21902319
TI  - Controlling the phase of a light beam with a single molecule.
AB  - We employ heterodyne interferometry to investigate the effect of a single organic
      molecule on the phase of a propagating laser beam. We report on the first phase
      contrast images of individual molecules and demonstrate a single-molecule electro
      optical phase switch by applying a voltage to the microelectrodes embedded in the
      sample. Our results may find applications in single-molecule holography, fast
      optical coherent signal processing, and single-emitter quantum operations.

PMID- 21902320
TI  - Charge resonance enhanced ionization of CO2 probed by laser Coulomb explosion
      imaging.
AB  - The process by which a molecule in an intense laser field ionizes more
      efficiently as its bond length increases towards a critical distance R(c) is
      known as charge resonance enhanced ionization (CREI). We make a series of
      measurements of this process for CO(2), by varying pulse duration from 7 to 200
      fs, in order to identify the charge states and time scales involved. We find that
      for the 4+ and higher charge states, 100 fs is the time scale required to reach
      the critical geometry <R(CO)> ~ 2.1 A and <theta(OCO)> ~ 163 degrees 
      (equilibrium CO(2) geometry is <R(CO)> ~ 1.16 A and <theta(OCO)> ~ 172 degrees ).
      The CO(2)(3+) molecule, however, appears always to begin dissociation from closer
      than 1.7 A indicating that dynamics on charge states lower than 3+ is not
      sufficient to initiate CREI. Finally, we make quantum ab initio calculations of
      ionization rates for CO(2) and identify the electronic states responsible for
      CREI.

PMID- 21902321
TI  - Charge state dependent energy deposition by ion impact.
AB  - We report on a measurement of craters in thin dielectric films formed by Xe(Q+)
      (26 <= Q <= 44) projectiles. Tunnel junction devices with ion-irradiated barriers
      were used to amplify the effect of charge-dependent cratering through the
      exponential dependence of tunneling conductance on barrier thickness. Electrical
      conductance of a crater sigma(c)(Q) increased by 4 orders of magnitude (7.9 * 10(
      4) MUS to 6.1 MUS) as Q increased, corresponding to crater depths ranging from 2
      to 11 A. By employing a heated spike model, we determine that the energy required
      to produce the craters spans from 8 to 25 keV over the investigated charge
      states. Considering energy from preequilibrium nuclear and electronic stopping as
      well as neutralization, we find that at least (27 +/- 2)% of available projectile
      neutralization energy is deposited into the thin film during impact.

PMID- 21902322
TI  - Photon blockade effect in optomechanical systems.
AB  - We analyze the photon statistics of a weakly driven optomechanical system and
      discuss the effect of photon blockade under single-photon strong coupling
      conditions. We present an intuitive interpretation of this effect in terms of
      displaced oscillator states and derive analytic expressions for the cavity
      excitation spectrum and the two-photon correlation function g(2)(0). Our results
      predict the appearance of nonclassical photon correlations in the combined strong
      coupling and sideband resolved regime and provide a first detailed understanding
      of photon-photon interactions in strong coupling optomechanics.

PMID- 21902323
TI  - Single-photon optomechanics.
AB  - Optomechanics experiments are rapidly approaching the regime where the radiation
      pressure of a single photon displaces the mechanical oscillator by more than its
      zero-point uncertainty. We show that in this limit the power spectrum has
      multiple sidebands and that the cavity response has several resonances in the
      resolved-sideband limit. Using master-equation simulations, we also study the
      crossover from the weak-coupling many-photon to the single-photon strong-coupling
      regime. Finally, we find non-Gaussian steady states of the mechanical oscillator
      when multiphoton transitions are resonant. Our study provides the tools to detect
      and take advantage of this novel regime of optomechanics.

PMID- 21902324
TI  - Octave spanning tunable frequency comb from a microresonator.
AB  - We report the generation of an octave-spanning optical frequency comb in a
      continuous wave laser pumped microresonator. The generated comb spectrum covers
      the wavelength range from 990 to 2170 nm without relying on additional external
      broadening. Continuous tunability of the generated frequency comb over more than
      an entire free spectral range is demonstrated. Moreover, the linewidth of
      individual optical comb components and its relation to the pump laser phase noise
      is studied. The ability to derive octave-spanning spectra from microresonator
      comb generators represents a key step towards f-2f self-referencing of
      microresonator-based optical frequency combs.

PMID- 21902325
TI  - Controlling the second harmonic in a phase-matched negative-index metamaterial.
AB  - Nonlinear metamaterials have been predicted to support new and exciting domains
      in the manipulation of light, including novel phase-matching schemes for wave
      mixing. Most notable is the so-called nonlinear-optical mirror, in which a
      nonlinear negative-index medium emits the generated frequency towards the source
      of the pump. In this Letter, we experimentally demonstrate the nonlinear-optical
      mirror effect in a bulk negative-index nonlinear metamaterial, along with two
      other novel phase-matching configurations, utilizing periodic poling to switch
      between the three phase-matching domains.

PMID- 21902326
TI  - Ultraconfined interlaced plasmons.
AB  - We describe a mesoscopic excitation in strongly coupled grids of metallic
      nanorods, resulting from the hybridization of weakly bounded plasmons. It is
      shown both theoretically and experimentally that the characteristic spatial scale
      of the interlaced plasmons is determined by geometrical features, rather than
      from the electrical length of the nanorods, and that due to their wide band
      nature, weak sensitivity to metallic absorption, and subwavelength mode sizes,
      such plasmons may have exciting applications in waveguiding in the nanoscale.

PMID- 21902327
TI  - Raman lasing with a cold atom gain medium in a high-finesse optical cavity.
AB  - We demonstrate a Raman laser using cold (87)Rb atoms as the gain medium in a high
      finesse optical cavity. We observe robust continuous wave lasing in the atypical
      regime where single atoms can considerably affect the cavity field. Consequently,
      we discover unusual lasing threshold behavior in the system causing jumps in
      lasing power, and propose a model to explain the effect. We also measure the
      intermode laser linewidth, and observe values as low as 80 Hz. The tunable gain
      properties of this laser suggest multiple directions for future research.

PMID- 21902328
TI  - Acoustic resonators for far-field control of sound on a subwavelength scale.
AB  - We prove experimentally that broadband sounds can be controlled and focused at
      will on a subwavelength scale by using acoustic resonators. We demonstrate our
      approach in the audible range with soda cans, that is, Helmholtz resonators, and
      commercial computer speakers. We show that diffraction-limited sound fields
      convert efficiently into subdiffraction modes in the collection of cans that can
      be controlled coherently in order to obtain focal spots as thin as 1/25 of a
      wavelength in air. We establish that subwavelength acoustic pressure spots are
      responsible for a strong enhancement of the acoustic displacement at focus, which
      permits us to conclude with a visual experiment exemplifying the interest of our
      concept for subwavelength sensors and actuators.

PMID- 21902329
TI  - Modal spectra extracted from nonequilibrium fluid patterns in laboratory
      experiments on Rayleigh-Benard convection.
AB  - We describe a method to extract from experimental data the important dynamical
      modes in spatiotemporal patterns in a system driven out of thermodynamic
      equilibrium. Using a novel optical technique for controlling fluid flow, we
      create an experimental ensemble of Rayleigh-Benard convection patterns with
      nearby initial conditions close to the onset of secondary instability. An
      analysis of the ensemble evolution reveals the spatial structure of the dominant
      modes of the system as well as the corresponding growth rates. The extracted
      modes are related to localized versions of instabilities found in the ideal
      unbounded system. The approach may prove useful in describing instability in
      experimental systems as a step toward prediction and control.

PMID- 21902330
TI  - Super-Alfvenic propagation of substorm reconnection signatures and Poynting flux.
AB  - The propagation of reconnection signatures and their associated energy are
      examined using kinetic particle-in-cell simulations and Cluster satellite
      observations. It is found that the quadrupolar out-of-plane magnetic field near
      the separatrices is associated with a kinetic Alfven wave. For magnetotail
      parameters, the parallel propagation of this wave is super-Alfvenic (V(?) ~ 1500
      5500 km/s) and generates substantial Poynting flux (S ~ 10(-5)-10(-4) W/m(2))
      consistent with Cluster observations of magnetic reconnection. This Poynting flux
      substantially exceeds that due to frozen-in ion bulk outflows and is sufficient
      to generate white light aurora in Earth's ionosphere.

PMID- 21902331
TI  - Rapid breakdown mechanisms of open air nanosecond dielectric barrier discharges.
AB  - The discharge initiation mechanism of nanosecond dielectric barrier discharges in
      open air has been clarified with time-dependent measurement of the discharge
      electric field by electric-field-induced coherent Raman scattering and optical
      emission. Our experimental observations have revealed that, in the prebreakdown
      phase of a nanosecond dielectric barrier discharge, the externally applied fast
      rising electric field is strongly enhanced near the cathode due to large
      accumulation of space charge, which then strongly enhances ionization near the
      cathode. Once a sufficiently large number of ionizations take place, the location
      of peak ionization forms a front and propagates toward the cathode with strong
      optical emission, which establishes the discharge. This process is essentially
      different from the well-known Townsend mechanism for slower discharges.

PMID- 21902332
TI  - Control of energy spread and dark current in proton and ion beams generated in
      high-contrast laser solid interactions.
AB  - By using temporal pulse shaping of high-contrast, short pulse laser interactions
      with solid density targets at intensities of 2 * 10(21) W cm(-2) at a 45 degrees 
      incident angle, we show that it is possible to reproducibly generate
      quasimonoenergetic proton and ion energy spectra. The presence of a short pulse
      prepulse 33 ps prior to the main pulse produced proton spectra with an energy
      spread between 25% and 60% (DeltaE/E) with energy of several MeV, with light ions
      becoming quasimonoenergetic for 50 nm targets. When the prepulse was removed, the
      energy spectra was broad. Numerical simulations suggest that expansion of the
      rear-side contaminant layer allowed for density conditions that prevented the
      protons from being screened from the sheath field, thus providing a low energy
      cutoff in the observed spectra normal to the target surface.

PMID- 21902333
TI  - Magnetically guided fast electrons in cylindrically compressed matter.
AB  - Fast electrons produced by a 10 ps, 160 J laser pulse through laser-compressed
      plastic cylinders are studied experimentally and numerically in the context of
      fast ignition. K(alpha)-emission images reveal a collimated or scattered electron
      beam depending on the initial density and the compression timing. A numerical
      transport model shows that implosion-driven electrical resistivity gradients
      induce strong magnetic fields able to guide the electrons. The good agreement
      with measured beam sizes provides the first experimental evidence for fast
      electron magnetic collimation in laser-compressed matter.

PMID- 21902334
TI  - Anisotropic ion heating and tail generation during tearing mode magnetic
      reconnection in a high-temperature plasma.
AB  - Complementary measurements of ion energy distributions in a magnetically confined
      high-temperature plasma show that magnetic reconnection results in both
      anisotropic ion heating and the generation of suprathermal ions. The anisotropy,
      observed in the C(+6) impurity ions, is such that the temperature perpendicular
      to the magnetic field is larger than the temperature parallel to the magnetic
      field. The suprathermal tail appears in the majority ion distribution and is well
      described by a power law to energies 10 times the thermal energy. These
      observations may offer insight into the energization process.

PMID- 21902335
TI  - Bose-Einstein condensate in a honeycomb optical lattice: fingerprint of
      superfluidity at the Dirac point.
AB  - Mean-field Bloch bands of a Bose-Einstein condensate in a honeycomb optical
      lattice are computed. We find that the topological structure of the Bloch bands
      at the Dirac point is changed completely by atomic interaction of arbitrary small
      strength: the Dirac point is extended into a closed curve and an intersecting
      tube structure arises around the original Dirac point. These tubed Bloch bands
      are caused by the superfluidity of the system. Furthermore, they imply the
      inadequacy of the tight-binding model to describe an interacting Boson system
      around the Dirac point and the breakdown of adiabaticity by interaction of
      arbitrary small strength.

PMID- 21902336
TI  - Simultaneous measurements of the torsional oscillator anomaly and thermal
      conductivity in solid 4He.
AB  - In these torsional oscillator experiments, the samples of solid (4)He were
      characterized by measuring their thermal conductivity. Polycrystalline samples of
      helium of either high isotopic purity or natural concentration of (3)He were
      grown in an annular container by the blocked-capillary method and investigated
      before and after annealing. No correlation has been found between the magnitude
      of the low-temperature shift of the torsional oscillator frequency and the amount
      of crystalline defects as measured by the thermal conductivity. In samples with
      the natural (3)He concentration, a substantial excess thermal conductivity over
      the usual T(3) dependence was observed below 120 mK.

PMID- 21902337
TI  - Roton-roton crossover in strongly correlated dipolar Bose-Einstein condensates.
AB  - We study the pair correlations and excitations of a dipolar Bose gas layer. The
      anisotropy of the dipole-dipole interaction allows us to tune the strength of
      pair correlations from strong to weak perpendicular and weak to strong parallel
      to the layer by increasing the perpendicular trap frequency. This change is
      accompanied by a roton-roton crossover in the spectrum of collective excitations,
      from a roton caused by the head-to-tail attraction of dipoles to a roton caused
      by the side-by-side repulsion, while there is no roton excitation for
      intermediate trap frequencies. We discuss the nature of these two kinds of rotons
      and the relation to instabilities of dipolar Bose gases. In both regimes of trap
      frequencies where rotons occur, we observe strong damping of collective
      excitations by decay into two rotons.

PMID- 21902338
TI  - Selective alignment of carbon nanotubes on sapphire surfaces: bond formation
      between nanotubes and substrates.
AB  - We present our first-principles total-energy calculations performed for carbon
      nanotubes (CNTs) on sapphire substrates. We find that the formation of covalent
      and partly ionic bonds between Al and C atoms on the Al-rich surfaces causes the
      selective alignment of CNTs, this being the principal reason for the CNT growth
      along particular crystallographic directions. We also find that the van der Waals
      interaction which is important on the stoichiometric surfaces produces no
      directional preference. The characteristic features in the electron states of the
      CNT on the substrate are clarified.

PMID- 21902339
TI  - Low-energy termination of graphene edges via the formation of narrow nanotubes.
AB  - We demonstrate that free graphene sheet edges can curl back on themselves,
      reconstructing as nanotubes. This results in lower formation energies than any
      other nonfunctionalized edge structure reported to date in the literature. We
      determine the critical tube size and formation barrier and compare with density
      functional simulations of other edge terminations including a new reconstructed
      Klein edge. Simulated high resolution electron microscopy images show why such
      rolled edges may be difficult to detect. Rolled zigzag edges serve as metallic
      conduction channels, separated from the neighboring bulk graphene by a chain of
      insulating sp(3)-carbon atoms, and introduce van Hove singularities into the
      graphene density of states.

PMID- 21902340
TI  - Inference and phase transitions in the detection of modules in sparse networks.
AB  - We present an asymptotically exact analysis of the problem of detecting
      communities in sparse random networks generated by stochastic block models. Using
      the cavity method of statistical physics and its relationship to belief
      propagation, we unveil a phase transition from a regime where we can infer the
      correct group assignments of the nodes to one where these groups are
      undetectable. Our approach yields an optimal inference algorithm for detecting
      modules, including both assortative and disassortative functional modules,
      assessing their significance, and learning the parameters of the underlying block
      model. Our algorithm is scalable and applicable to real-world networks, as long
      as they are well described by the block model.

PMID- 21902341
TI  - Glass transitions in quasi-two-dimensional suspensions of colloidal ellipsoids.
AB  - We observed a two-step glass transition in monolayers of colloidal ellipsoids by
      video microscopy. The glass transition in the rotational degree of freedom was at
      a lower density than that in the translational degree of freedom. Between the two
      transitions, ellipsoids formed an orientational glass. Approaching the respective
      glass transitions, the rotational and translational fastest-moving particles in
      the supercooled liquid moved cooperatively and formed clusters with power-law
      size distributions. The mean cluster sizes diverge in power law as they approach
      the glass transitions. The clusters of translational and rotational fastest
      moving ellipsoids formed mainly within pseudonematic domains and around the
      domain boundaries, respectively.

PMID- 21902342
TI  - Dynamical correlation length and relaxation processes in a glass former.
AB  - We investigate the relaxation process and the dynamical heterogeneities of the
      kinetically constrained Kob-Andersen lattice glass model and show that these are
      characterized by different time scales. The dynamics is well described within the
      diffusing defect paradigm, which suggests that we relate the relaxation process
      to a reverse-percolation transition. This allows for a geometrical interpretation
      of the relaxation process and of the different time scales.

PMID- 21902343
TI  - Experimental verification of rapid, sporadic particle motions by direct imaging
      of glassy colloidal systems.
AB  - We analyze data from confocal microscopy experiments of a colloidal suspension to
      validate predictions of rapid sporadic events responsible for structural
      relaxation in a glassy sample. The trajectories of several thousand colloidal
      particles are analyzed, confirming the existence of such rapid events responsible
      for the structural relaxation of significant regions of the sample, and
      complementing prior observations of dynamical heterogeneity. Thus, our results
      provide the first direct experimental verification of the emergence of relatively
      compact clusters of mobility which allow the dynamics to transition between the
      large periods of local confinement within its potential energy surface, in good
      agreement with the picture envisioned long ago by Adam and Gibbs and Goldstein.

PMID- 21902344
TI  - Anharmonicity and quantum effects in thermal expansion of an Invar alloy.
AB  - We have investigated the anharmonicity and quantum effects in the Invar alloy
      Fe(64.6)Ni(35.4) that shows anomalously small thermal expansion. We have
      performed Fe and Ni K-edge extended x-ray-absorption fine-structure spectroscopic
      measurements and the computational simulations based on the path-integral
      effective-classical-potential theory. The first nearest-neighbor (NN) shells
      around Fe show almost no thermal expansion, while those around Ni exhibit
      meaningful but smaller expansion than that of fcc Ni. At low temperature, the
      quantum effect is found to play an essentially important role, which is confirmed
      by comparing the quantum-mechanical simulations to the classical ones. The
      anharmonicity (asymmetric distribution) clearly exists for all the first NN
      shells as in normal thermal expansion systems, implying the breakdown of the
      direct correspondence between thermal expansion and anharmonicity.

PMID- 21902345
TI  - Defects in heavy-fermion materials: unveiling strong correlations in real space.
AB  - Defects provide important insight into the complex electronic and magnetic
      structure of heavy-fermion materials by inducing qualitatively different real
      space perturbations in the electronic and magnetic correlations of the system.
      These perturbations possess direct experimental signatures in the local density
      of states, such as an impurity bound state, and the nonlocal spin susceptibility.
      Moreover, highly nonlinear quantum interference between defect-induced
      perturbations can drive the system through a first-order phase transition to a
      novel inhomogeneous ground state.

PMID- 21902346
TI  - Numerical study of the localization length critical index in a network model of
      plateau-plateau transitions in the quantum Hall effect.
AB  - We calculate numerically the localization length critical index within the
      Chalker-Coddington model of the plateau-plateau transitions in the quantum Hall
      effect. We report a finite-size scaling analysis using both the traditional power
      law corrections to the scaling function and the inverse logarithmic ones, which
      provided a more stable fit resulting in the localization length critical index nu
      = 2.616 +/- 0.014. We observe an increase of the critical exponent nu with the
      system size, which is possibly the origin of discrepancies with early results
      obtained for smaller systems.

PMID- 21902347
TI  - Photoinduced phase transitions by time-resolved far-infrared spectroscopy in
      V2O3.
AB  - Using time-resolved far-infrared spectroscopy, we observe multiple routes for
      photoinduced phase transitions in V(2)O(3). This includes (i) a photothermal
      antiferromagnetic to paramagnetic transition and (ii) an incipient strain
      generated paramagnetic metal to paramagnetic insulator transition, which
      manifests as coherent oscillations in the far-infrared conductivity. The ~100 ps
      conductivity oscillation results from coherent acoustic phonon modulation of the
      bandwidth W. Our results indicate that poor metals are particularly amenable to
      coherent strain control of their electronic properties.

PMID- 21902348
TI  - Determination of the Co valence in bilayer hydrated superconducting NaxCoO2 .
      yH2O by soft x-ray absorption spectroscopy.
AB  - We addressed the so-far unresolved issue concerning the Co valence in the
      superconducting bilayer hydrated Na(x)CoO(2) . yH(2)O (x~0.35, y~1.3) using soft
      x-ray absorption spectroscopy at the Co-L(2,3) and O-K edges. We find that the
      valence state of the Co lies in a narrow range from +3.3 to +3.4 for all studied
      Na(x)CoO(2) . yH(2)O samples and their deuterated analogue with T(c)'s ranging
      from 3.8 to 4.7 K. These valence values are far from the often claimed +3.7, the
      number based on the Na content only. We propose to modify the phase diagram
      accordingly, where the basic electronic structure of the superconducting phase is
      very close to that of the Na(0.7)CoO(2) system, suggesting that the presence of
      in-plane spin fluctuations could play an important role for the
      superconductivity.

PMID- 21902349
TI  - Room temperature ultralow threshold GaN nanowire polariton laser.
AB  - We report ultralow threshold polariton lasing from a single GaN nanowire strongly
      coupled to a large-area dielectric microcavity. The threshold carrier density is
      3 orders of magnitude lower than that of photon lasing observed in the same
      device, and 2 orders of magnitude lower than any existing room-temperature
      polariton devices. Spectral, polarization, and coherence properties of the
      emission were measured to confirm polariton lasing.

PMID- 21902350
TI  - Hall-effect measurements probing the degree of charge-carrier delocalization in
      solution-processed crystalline molecular semiconductors.
AB  - Intramolecular structure and intermolecular packing in crystalline molecular
      semiconductors should have profound effects on the charge-carrier wave function,
      but simple drift mobility measurements are not very sensitive to this. Here we
      show that differences in the Hall resistance of two soluble pentacene derivatives
      can be explained with different degrees of carrier delocalization being limited
      by thermal lattice fluctuations. A combination of Hall measurements, optical
      spectroscopy, and theoretical simulations provides a powerful probe of structure
      property relationships at a molecular level.

PMID- 21902351
TI  - Time-reversal-symmetry-broken quantum spin Hall effect.
AB  - The quantum spin Hall (QSH) state of matter is usually considered to be protected
      by time-reversal (TR) symmetry. We investigate the fate of the QSH effect in the
      presence of the Rashba spin-orbit coupling and an exchange field, which break
      both inversion and TR symmetries. It is found that the QSH state characterized by
      nonzero spin Chern numbers C(+/-) = +/-1 persists when the TR symmetry is broken.
      A topological phase transition from the TR-symmetry-broken QSH phase to a quantum
      anomalous Hall phase occurs at a critical exchange field, where the bulk band gap
      just closes. It is also shown that the transition from the TR-symmetry-broken QSH
      phase to an ordinary insulator state cannot happen without closing the band gap.

PMID- 21902352
TI  - Ab initio calculation of the Gilbert damping parameter via the linear response
      formalism.
AB  - A Kubo-Greenwood-like equation for the Gilbert damping parameter alpha is
      presented that is based on the linear response formalism. Its implementation
      using the fully relativistic Korringa-Kohn-Rostoker band structure method in
      combination with coherent potential approximation alloy theory allows it to be
      applied to a wide range of situations. This is demonstrated with results obtained
      for the bcc alloy system Fe(1-x)Co(x) as well as for a series of alloys of
      Permalloy with 5d transition metals. To account for the thermal displacements of
      atoms as a scattering mechanism, an alloy-analogy model is introduced. The
      corresponding calculations for Ni correctly describe the rapid change of alpha
      when small amounts of substitutional Cu are introduced.

PMID- 21902353
TI  - Spin pumping at the magnetic insulator (YIG)/normal metal (Au) interfaces.
AB  - Spin injection across the ferrimagnetic insulator (YIG)/normal metal (Au)
      interface was studied by ferromagnetic resonance. The spin mixing conductance was
      determined by comparing the Gilbert damping in bare YIG films with those covered
      by a Au/Fe/Au structure. The Fe layer in Au/Fe/Au acted as a spin sink as
      displayed by an increased Gilbert damping parameter alpha compared to that in the
      bare YIG. In particular, for the 9.0  nm  YIG/2.0 nm Au/4.3 nm Fe/6.1 nm Au
      structure, the YIG and Fe films were coupled by an interlayer exchange coupling,
      and the exchange coupled YIG exhibited an increased Gilbert damping compared to
      the bare YIG. This relationship between static and dynamic coupling provides
      direct evidence for spin pumping. The transfer of spin momentum across the YIG
      interface is surprisingly efficient with the spin mixing conductance g(??) ? 1.2
      * 10(14) cm(-2).

PMID- 21902354
TI  - Validity of the Einstein relation in disordered organic semiconductors.
AB  - It is controversial whether energetic disorder in semiconductors is already
      sufficient to violate the classical Einstein relation, even in the case of
      thermal equilibrium. We demonstrate that the Einstein relation is violated only
      under nonequilibrium conditions due to deeply trapped carriers, as in diffusion
      driven current measurements on organic single-carrier diodes. Removal of these
      deeply trapped carriers by recombination unambiguously proves the validity of the
      Einstein relation in disordered semiconductors in thermal (quasi)equilibrium.

PMID- 21902355
TI  - Possible lattice distortions in the hubbard model for graphene.
AB  - The Hubbard model on the honeycomb lattice is a well-known model for graphene.
      Equally well known is the Peierls type of instability of the lattice bond
      lengths. In the context of these two approximations we ask and answer the
      question of the possible lattice distortions for graphene in zero magnetic field.
      The answer is that in the thermodynamic limit only periodic, reflection-symmetric
      distortions are allowed and these have at most 6 atoms per unit cell as compared
      to two atoms for the undistorted lattice.

PMID- 21902356
TI  - Electronic versus lattice match for metal-semiconductor epitaxial growth: Pb on
      Ge(111).
AB  - Lattice match is important for epitaxial growth. We show that a competing
      mechanism, electronic match, can dominate at small film thicknesses for metal
      semiconductor systems, where quantum confinement and symmetry requirements may
      favor a different growth pattern. For Pb(111) on Ge(111), an accidental lattice
      match leads to a ?3 * ?3 configuration involving a 30 degrees  in-plane rotation
      at large film thicknesses, but it gives way to an incommensurate (1 * 1)
      configuration at small film thickness. The transformation follows an
      approximately inverse-film-thickness dependence with superimposed bilayer
      oscillations.

PMID- 21902357
TI  - Lifshitz transition across the Ag/Cu(111) superlattice band gap tuned by
      interface doping.
AB  - The two-dimensional, free-electron-like band structure of noble metal surfaces
      can be radically transformed by appropriate nanostructuration. A case example is
      the triangular dislocation network that characterizes the epitaxial Ag/Cu(111)
      system, which exhibits a highly featured band topology with a full band gap above
      E(F) and a hole-pocket-like Fermi surface. Here we show that controlled doping of
      the Ag/Cu(111) interface with Au allows one to observe a complete Lifshitz
      transition at 300 K; i.e., the hole pockets fill up, the band gap entirely shifts
      across E(F), and the Fermi surface becomes electron-pocket-like.

PMID- 21902358
TI  - Observation of nonconventional spin waves in composite-fermion ferromagnets.
AB  - We find unexpected low energy excitations of fully spin-polarized composite
      fermion ferromagnets in the fractional quantum Hall liquid, resulting from a
      complex interplay between a topological order manifesting through new energy
      levels and a magnetic order due to spin polarization. The lowest energy modes,
      which involve spin reversal, are remarkable in displaying unconventional negative
      dispersion at small momenta followed by a deep roton minimum at larger momenta.
      This behavior results from a nontrivial mixing of spin-wave and spin-flip modes
      creating a spin-flip excitonic state of composite-fermion particle-hole pairs.
      The striking properties of spin-flip excitons imply highly tunable mode couplings
      that enable fine control of topological states of itinerant two-dimensional
      ferromagnets.

PMID- 21902359
TI  - Measurements of the anisotropic in-plane resistivity of underdoped FeAs-based
      pnictide superconductors.
AB  - We systematically investigated the in-plane resistivity anisotropy of electron
      underdoped EuFe(2-x)Co(x)As(2) and BaFe(2-x)Co(x)As(2) and hole-underdoped Ba(1
      x)K(x)Fe(2)As(2). Large in-plane resistivity anisotropy was found in the former
      samples, while tiny in-plane resistivity anisotropy was detected in the latter
      ones. When it is detected, the anisotropy starts above the structural transition
      temperature and increases smoothly through it. As the temperature is lowered
      further, the anisotropy takes a dramatic enhancement through the magnetic
      transition temperature. We found that the anisotropy is universally tied to the
      presence of T-linear behavior of resistivity. Our results demonstrate that the
      nematic state is caused by electronic degrees of freedom, and the microscopic
      orbital involvement in the magnetically ordered state must be fundamentally
      different between the hole- and electron-doped materials.

PMID- 21902360
TI  - Optical nonreciprocity in magnetic structures related to high-Tc superconductors.
AB  - Rotation of the plane of polarization of reflected light (Kerr effect) is a
      direct manifestation of broken time-reversal symmetry and is generally associated
      with the appearance of a ferromagnetic moment. Here I identify magnetic
      structures that may arise within the unit cell of cuprate superconductors that
      generate polarization rotation despite the absence of a net moment. For these
      magnetic symmetries the Kerr effect is mediated by magnetoelectric coupling,
      which can arise when antiferromagnetic order breaks inversion symmetry. The
      structures identified are candidates for a time-reversal breaking phase in the
      pseudogap regime of the cuprates.

PMID- 21902361
TI  - Origin of excess low-energy states in a disordered superconductor in a Zeeman
      field.
AB  - Tunneling density of states measurements of disordered superconducting Al films
      in high Zeeman fields reveal a significant population of subgap states which
      cannot be explained by standard BCS theory. We provide a natural explanation of
      these excess states in terms of a novel disordered Larkin-Ovchinnikov phase that
      occurs near the spin-paramagnetic transition at the Chandrasekhar-Clogston
      critical field. The disordered Larkin-Ovchinnikov superconductor is characterized
      by a pairing amplitude that changes sign at domain walls. These domain walls
      carry magnetization and support Andreev bound states that lead to distinct
      spectral signatures at low energy.

PMID- 21902362
TI  - Quantum phase diffusion in a small underdamped Josephson junction.
AB  - Quantum phase diffusion in a small underdamped Nb/AlO(x)/Nb junction (~0.4
      MUm(2)) is demonstrated in a wide temperature range of 25-140 mK where
      macroscopic quantum tunneling (MQT) is the dominant escape mechanism. We propose
      a two-step transition model to describe the switching process in which the escape
      rate out of the potential well and the transition rate from phase diffusion to
      the running state are considered. The transition rate extracted from the
      experimental switching current distribution follows the predicted Arrhenius law
      in the thermal regime but is greatly enhanced when MQT becomes dominant.

PMID- 21902363
TI  - Universality classes of magnetic domain wall motion.
AB  - We examine magnetic domain wall motion in metallic nanowires Pt-Co-Pt. Regardless
      of whether the motion is driven by either magnetic fields or current, all
      experimental data fall onto a single universal curve in the creep regime,
      implying that both the motions belong to the same universality class. This result
      is in contrast to the report on magnetic semiconductor (Ga,Mn)As exhibiting two
      different universality classes. Our finding signals the possible existence of yet
      other universality classes which go beyond the present understanding of the
      statistical mechanics of driven interfaces.

PMID- 21902364
TI  - Entanglement entropy of critical spin liquids.
AB  - Quantum spin liquids are phases of matter whose internal structure is not
      captured by a local order parameter. Particularly intriguing are critical spin
      liquids, where strongly interacting excitations control low energy properties.
      Here we calculate their bipartite entanglement entropy that characterizes their
      quantum structure. In particular we calculate the Renyi entropy S(2) on model
      wave functions obtained by Gutzwiller projection of a Fermi sea. Although the
      wave functions are not sign positive, S(2) can be calculated on relatively large
      systems (>324 spins) using the variational Monte Carlo technique. On the
      triangular lattice we find that entanglement entropy of the projected Fermi sea
      state violates the boundary law, with S(2) enhanced by a logarithmic factor. This
      is an unusual result for a bosonic wave function reflecting the presence of
      emergent fermions. These techniques can be extended to study a wide class of
      other phases.

PMID- 21902365
TI  - Giant effect of uniaxial pressure on magnetic domain populations in multiferroic
      bismuth ferrite.
AB  - Neutron diffraction is used to show that small (~7 MPa, or 70 bar) uniaxial
      pressure produces significant changes in the populations of magnetic domains in a
      single crystal of 2% Nd-doped bismuth ferrite. The magnetic easy plane of the
      domains converted by the pressure is rotated 60 degrees  relative to its original
      position. These results demonstrate extreme sensitivity of the magnetic
      properties of multiferroic bismuth ferrite to tiny (less than 10(-4)) elastic
      strain, as well as weakness of the forces pinning the domain walls between the
      cycloidal magnetic domains in this material.

PMID- 21902366
TI  - Strong correlation of electronic and lattice excitations in GaAs/AlGaAs
      semiconductor quantum wells revealed by two-dimensional terahertz spectroscopy.
AB  - Coulomb-mediated interactions between intersubband excitations of electrons in
      GaAs/AlGaAs double quantum wells and longitudinal optical phonons are studied by
      two-dimensional spectroscopy in the terahertz frequency range. The multitude of
      diagonal and off-diagonal peaks in the 2D spectrum gives evidence of strong
      polaronic signatures in the nonlinear response. A quantitative theoretical
      analysis reveals a dipole coupling of electrons to the polar lattice that is much
      stronger than in bulk GaAs, due to a dynamic localization of the electron wave
      function by scattering processes.

PMID- 21902367
TI  - Spin-polarized Mn2+ emission from Mn-doped colloidal nanocrystals.
AB  - We report magnetophotoluminescence studies of strongly quantum-confined 0D
      diluted magnetic semiconductors (DMS), realized in Mn(2+)-doped ZnSe/CdSe core
      shell colloidal nanocrystals. In marked contrast to their 3D (bulk), 2D (quantum
      well), 1D (quantum wire), and 0D (self-assembled quantum dot) DMS counterparts,
      the ubiquitous yellow emission band from internal d-d ((4)T(1)->(6)A(1))
      transitions of the Mn(2+) ions in these nanocrystals is not suppressed in applied
      magnetic fields and does become circularly polarized. This polarization tracks
      the Mn(2+) magnetization, and is accompanied by a sizable energy splitting
      between right- and left-circular emission components that scales with the exciton
      Mn sp-d coupling strength (which, in turn, is tunable with nanocrystal size).
      These data highlight the influence of strong quantum confinement on both the
      excitation and the emission mechanisms of magnetic ions in DMS nanomaterials.

PMID- 21902368
TI  - Coupled magnetic-ferroelectric metal-insulator transition in epitaxially strained
      SrCoO3 from first principles.
AB  - First-principles calculations are presented for the epitaxial-strain dependence
      of the ground-state phase stability of perovskite SrCoO(3). Through the
      combination of the large spin-phonon coupling with polarization-strain coupling
      and the coupling of the band gap to the polar distortion, both tensile and
      compressive epitaxial strain are seen to drive the bulk ferromagnetic-metallic
      (FM-M) phase to antiferromagnetic-insulating-ferroelectric (AFM-I-FE) phases, the
      latter having unusually low elastic energy. For compressive strain, there is a
      single coupled magnetic-ferroelectric metal-insulator transition. At this phase
      boundary, cross responses to applied electric and magnetic fields and stresses
      are expected. In particular, a magnetic field or compressive uniaxial stress
      applied to the AFM-FE(z) phase could induce an insulator-metal transition, and an
      electric field applied to the FM-M phase could induce a metal-insulator
      transition.

PMID- 21902369
TI  - Structure conserving correlation and the Kohlrausch-Williams-Watts decay of the
      incoherent intermediate scattering function in simulated Ni(0.5)Zr(0.5) melt.
AB  - Results are presented about the origin of the Kohlrausch-Williams-Watts decay of
      the incoherent intermediate scattering function (ISF) in molecular dynamics
      simulated liquid Ni(0.5)Zr(0.5). By the concept of weakly effective particles
      (WEPs), we establish an interrelationship between ISF and particle dynamics.
      Temporal correlations in the action of WEPs act structure conserving, reflecting
      that immobile particles tend to remain immobile. Analysis of the related
      correlation function yields that these correlations account quantitatively for
      the stretched exponential like decay.

PMID- 21902370
TI  - Translocation of DNA molecules through nanopores with salt gradients: the role of
      osmotic flow.
AB  - Recent experiments of translocation of double-stranded DNA through nanopores [M.
      Wanunu et al., Nature Nanotech. 5, 160 (2009)] reveal that the DNA capture rate
      can be significantly influenced by a salt gradient across the pore. We show that
      osmotic flow combined with electrophoretic effects can quantitatively explain the
      experimental data on the salt-gradient dependence of the capture rate.

PMID- 21902371
TI  - Thermomechanics of DNA: theory of thermal stability under load.
AB  - A theory for thermomechanical behavior of homogeneous DNA at thermal equilibrium
      predicts critical temperatures for denaturation under torque and stretch, phase
      diagrams for stable B-DNA, supercoiling, optimally stable torque, and the
      overstretching transition as force-induced DNA melting. Agreement with available
      single molecule manipulation experiments is excellent.

PMID- 21902372
TI  - Dynamics of DNA replication in yeast.
AB  - We present a mathematical model for the spatial dynamics of DNA replication.
      Using this model we determine the probability distribution for the time at which
      each chromosomal position is replicated. From this we show, contrary to previous
      reports, that mean replication time curves cannot be used to directly determine
      origin parameters. We demonstrate that the stochastic nature of replication
      dynamics leaves a clear signature in experimentally measured population average
      data, and we show that the width of the activation time probability distribution
      can be inferred from this data. Our results compare favorably with experimental
      measurements in Saccharomyces cerevisae.

PMID- 21902373
TI  - Adhesive emulsion bilayers under an electric field: from unzipping to fusion.
AB  - Water-in-oil emulsion drops are formed and stabilized with phospholipids which
      can adhere and form a bilayer. Using microfluidics, adhesive drop pairs are then
      trapped and submitted to an ac electric field. We observe three distinct states
      as a function of the adhesion energy and the electric field intensity. The pair
      can be either stable, though slightly deformed, or unzip and separate, or
      coalesce. The frontiers between the different states directly reflect vesicle
      detachment forces and electroporation theories. The experimental approach that we
      propose for probing liquid interface wetting between monolayers allows us to
      finely tuned the tension in the bilayer and gives access to bilayer unzipping.

PMID- 21902374
TI  - Cluster crystals under shear.
AB  - We show that a distinct class of colloidal crystals, which consist of mutually
      overlapping particles, has a novel and universal response to steady shear. After
      a shear-banding regime at low shear rates, strings parallel to the flow direction
      form as shear grows, which order on a hexagonal crystal in the gradient-vorticity
      plane. At even higher shear, lateral fluctuations of the strings, enhanced by
      hydrodynamics, lead to a disordered, fluid state. Our results are based on
      appropriate simulation techniques that correctly account for hydrodynamics. We
      also find that shear vastly accelerates the nucleation rates of supercooled
      fluids into the cluster crystals.

PMID- 21902376
TI  - Totally asymmetric simple exclusion process on networks.
AB  - We study the totally asymmetric simple exclusion process (TASEP) on complex
      networks, as a paradigmatic model for transport subject to excluded volume
      interactions. Building on TASEP phenomenology on a single segment and borrowing
      ideas from random networks we investigate the effect of connectivity on
      transport. In particular, we argue that the presence of disorder in the topology
      of vertices crucially modifies the transport features of a network: irregular
      networks involve homogeneous segments and have a bimodal distribution of edge
      densities, whereas regular networks are dominated by shocks leading to a unimodal
      density distribution. The proposed numerical approach of solving for mean-field
      transport on networks provides a general framework for studying TASEP on large
      networks, and is expected to generalize to other transport processes.

PMID- 21902375
TI  - High-accuracy approximation of binary-state dynamics on networks.
AB  - Binary-state dynamics (such as the susceptible-infected-susceptible (SIS) model
      of disease spread, or Glauber spin dynamics) on random networks are accurately
      approximated using master equations. Standard mean-field and pairwise theories
      are shown to result from seeking approximate solutions of the master equations.
      Applications to the calculation of SIS epidemic thresholds and critical points of
      nonequilibrium spin models are also demonstrated.

PMID- 21902377
TI  - Bell inequalities with no quantum violation and unextendable product bases.
AB  - The strength of classical correlations is subject to certain constraints,
      commonly known as Bell inequalities. Violation of these inequalities is the
      manifestation of nonlocality-displayed, in particular, by quantum mechanics,
      meaning that quantum mechanics can outperform classical physics at tasks
      associated with such Bell inequalities. Interestingly, however, there exist
      situations in which this is not the case. We associate an intriguing class of
      bound entangled states, constructed from unextendable product bases with a wide
      family of tasks, for which (i) quantum correlations do not outperform the
      classical ones but (ii) there exist supraquantum nonsignaling correlations that
      do provide an advantage.

PMID- 21902378
TI  - Experimentally witnessing the quantumness of correlations.
AB  - The quantification of quantum correlations (other than entanglement) usually
      entails labored numerical optimization procedures also demanding quantum state
      tomographic methods. Thus it is interesting to have a laboratory friendly witness
      for the nature of correlations. In this Letter we report a direct experimental
      implementation of such a witness in a room temperature nuclear magnetic resonance
      system. In our experiment the nature of correlations is revealed by performing
      only few local magnetization measurements. We also compared the witness results
      with those for the symmetric quantum discord and we obtained a fairly good
      agreement.

PMID- 21902379
TI  - Time-dependent variational principle for quantum lattices.
AB  - We develop a new algorithm based on the time-dependent variational principle
      applied to matrix product states to efficiently simulate the real- and imaginary
      time dynamics for infinite one-dimensional quantum lattices. This procedure (i)
      is argued to be optimal, (ii) does not rely on the Trotter decomposition and thus
      has no Trotter error, (iii) preserves all symmetries and conservation laws, and
      (iv) has low computational complexity. The algorithm is illustrated by using both
      an imaginary-time and a real-time example.

PMID- 21902380
TI  - First observational tests of eternal inflation.
AB  - The eternal inflation scenario predicts that our observable Universe resides
      inside a single bubble embedded in a vast inflating multiverse. We present the
      first observational tests of eternal inflation, performing a search for
      cosmological signatures of collisions with other bubble universes in cosmic
      microwave background data from the WMAP satellite. We conclude that the WMAP 7
      year data do not warrant augmenting the cold dark matter model with a
      cosmological constant with bubble collisions, constraining the average number of
      detectable bubble collisions on the full sky N(s) < 1.6 at 68% C.L. Data from the
      Planck satellite can be used to more definitively test the bubble-collision
      hypothesis.

PMID- 21902381
TI  - Black hole evaporation rates without spacetime.
AB  - Verlinde recently suggested that gravity, inertia, and even spacetime may be
      emergent properties of an underlying thermodynamic theory. This vision was
      motivated in part by Jacobson's 1995 surprise result that the Einstein equations
      of gravity follow from the thermodynamic properties of event horizons. Taking a
      first tentative step in such a program, we derive the evaporation rate (or
      radiation spectrum) from black hole event horizons in a spacetime-free manner.
      Our result relies on a Hilbert space description of black hole evaporation,
      symmetries therein which follow from the inherent high dimensionality of black
      holes, global conservation of the no-hair quantities, and the existence of
      Penrose processes. Our analysis is not wedded to standard general relativity and
      so should apply to extended gravity theories where we find that the black hole
      area must be replaced by some other property in any generalized area theorem.

PMID- 21902382
TI  - Testing gravity using the environmental dependence of dark matter halos.
AB  - In this Letter, we investigate the environmental dependence of dark matter halos
      in theories which attempt to explain the accelerated expansion of the Universe by
      modifying general relativity (GR). Using high-resolution N-body simulations in
      f(R) gravity models which recover GR in dense environments by virtue of the
      chameleon mechanism, we find a significant difference, which depends on the
      environment, between the lensing and dynamical masses of dark matter halos. This
      environmental dependence of the halo properties can be used as a smoking gun to
      test GR observationally.

PMID- 21902383
TI  - Soliton-antisoliton pair production in particle collisions.
AB  - We propose a general semiclassical method for computing the probability of
      soliton-antisoliton pair production in particle collisions. The method is
      illustrated by explicit numerical calculations in a (1+1)-dimensional scalar
      field model. We find that the probability of the process is suppressed by an
      exponentially small factor which is almost constant at high energies.

PMID- 21902384
TI  - Precise determination of the f0(600) and f0(980) pole parameters from a
      dispersive data analysis.
AB  - We use our latest dispersive analysis of pipi scattering data and the very recent
      K(l4) experimental results to obtain the mass, width, and couplings of the two
      lightest scalar-isoscalar resonances. These parameters are defined from their
      associated poles in the complex plane. The analytic continuation to the complex
      plane is made in a model-independent way by means of once- and twice-subtracted
      dispersion relations for the partial waves, without any other theoretical
      assumption. We find the f(0)(600) pole at (457(-13))+14))-i(279(-7)(+11)) MeV and
      that of the f(0)(980) at (996 +/- 7)-i(25(-6)(+10)) MeV, whereas their respective
      couplings to two pions are 3.59(-0.13)(+0.11) and 2.3 +/- 0.2 GeV.

PMID- 21902385
TI  - Lattice QCD and the timelike pion form factor.
AB  - We present a formula that allows one to calculate the pion form factor in the
      timelike region 2m(pi) <= ?(s) <= 4m(pi) in lattice QCD. The form factor
      quantifies the contribution of two-pion states to the vacuum polarization. It
      must be known very accurately in order to reduce the theoretical uncertainty on
      the anomalous magnetic moment of the muon. At the same time, the formula
      constitutes a rare example where, in a restricted kinematic regime, the spectral
      function of a conserved current can be determined from Euclidean observables
      without an explicit analytic continuation.

PMID- 21902388
TI  - Similarity-transformed chiral NN + 3N interactions for the ab initio description
      of 12C and 16O.
AB  - We present first ab initio no-core shell model (NCSM) calculations using
      similarity renormalization group (SRG) transformed chiral two-nucleon (NN) plus
      three-nucleon (3N) interactions for nuclei throughout the p-shell, particularly
      (12)C and (16)O. By introducing an adaptive importance truncation for the NCSM
      model space and an efficient JT-coupling scheme for the 3N matrix elements, we
      are able to surpass previous NCSM studies including 3N interactions. We present
      ground and excited states in (12)C and (16)O for model spaces up to N(max) = 12
      including full 3N interactions. We analyze the contributions of induced and
      initial 3N interactions and probe induced 4N terms through the sensitivity of the
      energies on the SRG flow parameter. Unlike for light p-shell nuclei, SRG-induced
      4N contributions originating from the long-range two-pion terms of the chiral 3N
      interaction are sizable in (12)C and (16)O.

PMID- 21902387
TI  - Observation of transverse polarization asymmetries of charged pion pairs in e+e-
      annihilation near ?s = 10.58 GeV.
AB  - The interference fragmentation function translates the fragmentation of a quark
      with a transverse projection of the spin into an azimuthal asymmetry of two final
      state hadrons. In e(+)e(-) annihilation the product of two interference
      fragmentation functions is measured. We report nonzero asymmetries for pairs of
      charge-ordered pi(+)pi(-) pairs, which indicate a significant interference
      fragmentation function in this channel. The results are obtained from a 672 fb(
      1) data sample that contains 711 * 10(6) pi(+)pi(-) pairs and was collected at
      and near the Upsilon(4S) resonance, with the Belle detector at the KEKB
      asymmetric-energy e(+)e(-) collider.

PMID- 21902389
TI  - K(h)alpha1,2 x-ray hypersatellite line broadening as a signature of K-shell
      double photoionization followed by outer-shell ionization and excitation.
AB  - We propose a novel approach for the theoretical analysis of the photoinduced high
      resolution K(h)alpha(1,2) x-ray hypersatellite spectra, which allows us to obtain
      reliable values of lifetimes of the doubly K-shell ionized states and fundamental
      information about the relative role of K-shell double photoionization (DPI)
      mechanisms. It is demonstrated for the first time that the K(h)alpha(1,2)
      hypersatellite natural line broadening observed for selected metal atoms with 20
      <= Z <= 30 can be well reproduced quantitatively by taking into account the
      influences of the open-shell valence configuration (adopted from predictions of
      the band-structure method) and the outer-shell ionization and excitation
      following the DPI process.

PMID- 21902390
TI  - Few-body bound states in dipolar gases and their detection.
AB  - We consider dipolar interactions between heteronuclear molecules in a low
      dimensional setup consisting of two one-dimensional tubes. We demonstrate that
      attraction between molecules in different tubes can overcome intratube repulsion
      and complexes with several molecules in the same tube are stable. In situ
      detection schemes of the few-body complexes are proposed. We discuss extensions
      to many tubes and layers, and outline the implications on many-body physics.

PMID- 21902386
TI  - Single spin asymmetries in charged pion production from semi-inclusive deep
      inelastic scattering on a transversely polarized 3He Target at Q2 = 1.4-2.7 GeV2.
AB  - We report the first measurement of target single spin asymmetries in the semi
      inclusive (3)He(e,e'pi(+/-))X reaction on a transversely polarized target. The
      experiment, conducted at Jefferson Lab using a 5.9 GeV electron beam, covers a
      range of 0.16 < x < 0.35 with 1.4 < Q(2) < 2.7 GeV(2). The Collins and Sivers
      moments were extracted from the azimuthal angular dependence of the measured
      asymmetries. The pi(+/-) Collins moments for (3)He are consistent with zero,
      except for the pi(+) moment at x = 0.35, which deviates from zero by 2.3sigma.
      While the pi(-) Sivers moments are consistent with zero, the pi(+) Sivers moments
      favor negative values. The neutron results were extracted using the nucleon
      effective polarization and measured cross section ratios of proton to (3)He, and
      are largely consistent with the predictions of phenomenological fits and quark
      model calculations.

PMID- 21902391
TI  - Measurement of optical Feshbach resonances in an ideal gas.
AB  - Using a narrow intercombination line in alkaline earth atoms to mitigate large
      inelastic losses, we explore the optical Feshbach resonance effect in an
      ultracold gas of bosonic (88)Sr. A systematic measurement of three resonances
      allows precise determinations of the optical Feshbach resonance strength and
      scaling law, in agreement with coupled-channel theory. Resonant enhancement of
      the complex scattering length leads to thermalization mediated by elastic and
      inelastic collisions in an otherwise ideal gas. Optical Feshbach resonance could
      be used to control atomic interactions with high spatial and temporal resolution.

PMID- 21902392
TI  - Demonstration of a single-photon router in the microwave regime.
AB  - We have embedded an artificial atom, a superconducting transmon qubit, in an open
      transmission line and investigated the strong scattering of incident microwave
      photons (~6  GHz). When an input coherent state, with an average photon number
      N?1 is on resonance with the artificial atom, we observe extinction of up to
      99.6% in the forward propagating field. We use two-tone spectroscopy to study
      scattering from excited states and we observe electromagnetically induced
      transparency (EIT). We then use EIT to make a single-photon router, where we can
      control to what output port an incoming signal is delivered. The maximum on-off
      ratio is around 99% with a rise and fall time on the order of nanoseconds,
      consistent with theoretical expectations. The router can easily be extended to
      have multiple output ports and it can be viewed as a rudimentary quantum node, an
      important step towards building quantum information networks.

PMID- 21902393
TI  - Enhancement of laser interaction with vacuum for a large angular aperture.
AB  - We study the nonlinear interaction of laser light with vacuum for a large angular
      aperture at electromagnetic field strengths far below the Schwinger limit. The
      polarization and magnetization in vacuum irradiated by a focused laser beam
      clearly differ from those in matter. This is due to the dependence on the Lorentz
      invariant, which results in a ring-shaped radiation distribution in vacuum. The
      number of the radiated photons increases nonlinearly with increasing angular
      aperture.

PMID- 21902394
TI  - Proposal for an optical laser producing light at half the Josephson frequency.
AB  - We describe a superconducting device capable of producing laser light in the
      visible range at half of the Josephson generation frequency with the optical
      phase of the light locked to the superconducting phase difference. It consists of
      two single-level quantum dots embedded in a p-n semiconducting heterostructure
      and surrounded by a cavity supporting a resonant optical mode. We study
      decoherence and spontaneous switching in the device.

PMID- 21902395
TI  - Large optical-frequency shift of molecular radiation via coherent coupling to an
      off-resonance plasmon.
AB  - We demonstrate coherent optical coupling between molecular and plasmon resonances
      that are well separated in energy. In the presence of metallic nanoparticles, the
      second harmonic spectrum of organic dyes no longer peaks at the absorption
      wavelength but is instead blueshifted by 25 nm towards the localized plasmon
      resonance. The phase of the light generated by the dyes displays a large
      modulation across the plasmon resonance and no change across the molecular one.
      The second harmonic signal contributed by the nanoparticles, which is peaked at
      the plasmon frequency when no molecules are present, similarly displays a shift
      towards the molecular resonance in their presence. A model based on the interplay
      of the nonlinear optical near fields is able to account for these observations.

PMID- 21902396
TI  - Theory of the Anderson transition in the quasiperiodic kicked rotor.
AB  - We present the first microscopic theory of transport in quasiperiodically driven
      environments ("kicked rotors"), as realized in recent atom optic experiments. We
      find that the behavior of these systems depends sensitively on the value of a
      dimensionless Planck constant h: for irrational values of h/(4pi) they fall into
      the universality class of disordered electronic systems and we describe the
      corresponding localization phenomena. In contrast, for rational values the rotor
      Anderson insulator acquires an infinite (static) conductivity and turns into a
      "supermetal." We discuss the ensuing possibility of a metal-supermetal quantum
      phase transition.

PMID- 21902397
TI  - Transition from static to kinetic friction: insights from a 2D model.
AB  - We describe a 2D spring-block model for the transition from static to kinetic
      friction at an elastic-slider-rigid-substrate interface obeying a minimalistic
      friction law (Amontons-Coulomb). By using realistic boundary conditions, a number
      of previously unexplained experimental results on precursory microslip fronts are
      successfully reproduced. From the analysis of the interfacial stresses, we derive
      a prediction for the evolution of the precursor length as a function of the
      applied loads, as well as an approximate relationship between microscopic and
      macroscopic friction coefficients. We show that the stress buildup due to both
      elastic loading and microslip-related relaxations depends only weakly on the
      underlying shear crack propagation dynamics. Conversely, crack speed depends
      strongly on both the instantaneous stresses and the friction coefficients,
      through a nontrivial scaling parameter.

PMID- 21902398
TI  - Fluid flow control with transformation media.
AB  - We introduce a new concept for the manipulation of fluid flow around three
      dimensional bodies. Inspired by transformation optics, the concept is based on a
      mathematical idea of coordinate transformations and physically implemented with
      anisotropic porous media permeable to the flow of fluids. In two situations-for
      an impermeable object placed either in a free-flowing fluid or in a fluid-filled
      porous medium-we show that the object can be coated with an inhomogeneous,
      anisotropic permeable medium, such as to preserve the flow that would have
      existed in the absence of the object. The proposed fluid flow cloak eliminates
      downstream wake and compensates viscous drag, hinting at the possibility of novel
      propulsion techniques.

PMID- 21902399
TI  - Double cascade turbulence and Richardson dispersion in a horizontal fluid flow
      induced by Faraday waves.
AB  - We report the experimental observation of Richardson dispersion and a double
      cascade in a thin horizontal fluid flow induced by Faraday waves. The energy
      spectra and the mean spectral energy flux obtained from particle image
      velocimetry data suggest an inverse energy cascade with Kolmogorov type scaling
      E(k) ? k(gamma), gamma ~ -5/3 and an E(k) ? k(gamma), gamma ~ -3 enstrophy
      cascade. Particle transport is studied analyzing absolute and relative dispersion
      as well as the finite size Lyapunov exponent (FSLE) via the direct tracking of
      real particles and numerical advection of virtual particles. Richardson
      dispersion with <DeltaR(2)(t)> ? t(3) is observed and is also reflected in the
      slopes of the FSLE (Lambda ? DeltaR(-2/3)) for virtual and real particles.

PMID- 21902400
TI  - Motion of micrometer sized spherical particles exposed to a transient radial
      flow: attraction, repulsion, and rotation.
AB  - It is now accepted that the physical forces in ultrasonic cleaning are due to
      strongly pulsating bubbles driven by the sound field. Here we have a detailed
      look at bubble induced cleaning flow by analyzing the transport of an individual
      particle near an expanding and collapsing bubble. The induced particulate
      transport is compared with a force balance model. We find two important
      properties of the flow which explain why bubbles are effectively cleaning: During
      bubble expansion a strong shear layer loosens the particle from the surface
      through particle spinning and secondly an unsteady boundary layer generates an
      attractive force, thus collecting the contamination in the bubble's close
      proximity.

PMID- 21902401
TI  - Correlations in amplified four-wave mixing of matter waves.
AB  - The coherence properties of amplified matter waves generated by four-wave mixing
      (FWM) are studied using the Hanbury-Brown-Twiss method. We examine two limits. In
      the first case stimulated processes lead to the selective excitation of a pair of
      spatially separated modes, which we show to be second order coherent, while the
      second occurs when the FWM process is multimode, due to spontaneous scattering
      events which leads to incoherent matter waves. Amplified FWM is a promising
      candidate for fundamental tests of quantum mechanics where correlated modes with
      large occupations are required.

PMID- 21902402
TI  - Paramagnetic tunneling systems and their contribution to the polarization echo in
      glasses.
AB  - Startling magnetic effects on the spontaneous polarization echo in some silicate
      glasses at low and ultralow temperatures have been reported in the last decade or
      so. Though some progress in search of an explanation has been made by considering
      the nuclear quadrupole dephasing of tunneling particles, here we show that the
      effect of a magnetic field can be understood quantitatively by means of a special
      tunnel mechanism associated with paramagnetic impurities. For the Fe(3+)-, Cr(3+)
      , and Nd(3+)-contaminated glasses we provide reasonable fits to the published
      data as a function of applied magnetic field and temperature.

PMID- 21902403
TI  - Torsional response and dissipationless viscosity in topological insulators.
AB  - We consider the viscoelastic response of the electronic degrees of freedom in 2D
      and 3D topological insulators (TI's). Our primary focus is on the 2D Chern
      insulator which exhibits a bulk dissipationless viscosity analogous to the
      quantum Hall viscosity predicted in integer and fractional quantum Hall states.
      We show that the dissipationless viscosity is the response of a TI to torsional
      deformations of the underlying lattice geometry. The viscoelastic response also
      indicates that crystal dislocations in Chern insulators will carry momentum
      density. We briefly discuss generalizations to 3D which imply that time-reversal
      invariant TI's will exhibit a quantum Hall viscosity on their surfaces.

PMID- 21902404
TI  - Observation of a martensitic structural distortion in V, Nb, and Ta.
AB  - Thermal-expansion measurements of the Group 5 elements V, Nb, and Ta reveal a
      structural distortion below 300 K. Data for single-crystalline Nb and Ta display
      anisotropic thermal expansion, martensitic in character, that is inconsistent
      with cubic crystal structures at low temperature. Published results on V show
      similar behavior. Interstitial impurities suppress the transition.

PMID- 21902405
TI  - Nonequilibrium composition profiles of alloy quantum dots and their correlation
      with the growth mode.
AB  - Equilibrium composition profiles (CPs) of epitaxial alloy quantum dots (QDs) are
      well established theoretically. However nonequilibrium CPs may occur
      experimentally. Using an atomistic-strain-model Monte Carlo simulation method, we
      demonstrate a striking correlation between the nonequilibrium CPs of QDs and the
      kinetic growth mode: the layer-by-layer growth (LG) and faceted growth (FG) form
      a core-shell structure having the triangle core of the unstrained and V-shaped
      core of the strained component, respectively, and both are distinctly different
      from the equilibrium CP. Comparing simulations with experiments, we infer that
      the InGaAs dots on GaAs grow by FG, while GeSi dots on Si grow first by LG
      followed by FG. Our findings suggest a possible method for controlling the CPs of
      QDs by selecting the growth mode.

PMID- 21902406
TI  - Polarization dependence of palladium deposition on ferroelectric lithium niobate
      (0001) surfaces.
AB  - We investigate the effect of ferroelectric polarization direction on the
      geometric properties of Pd deposited on the positive and negative surfaces of
      LiNbO(3) (0001). We predict preferred geometries and diffusion properties of
      small Pd clusters using density functional theory, and use these calculations as
      the basis for kinetic Monte Carlo simulations of Pd deposition on a larger scale.
      Our results show that on the positive surface, Pd atoms favor a clustered
      configuration, while on the negative surface, Pd atoms are adsorbed in a more
      dispersed pattern due to suppression of diffusion and agglomeration. This
      suggests that the effect of LiNbO(3) polarization direction on the catalytic
      activity of Pd [J. Phys. Chem. 88, 1148 (1984)] is due, at least in part, to
      differences in adsorption geometry. Further investigations using these methods
      can aid the search for catalysts whose activities switch reversibly with the
      polarization of their ferroelectric substrates.

PMID- 21902407
TI  - Localization and critical diffusion of quantum dipoles in two dimensions.
AB  - We discuss quantum propagation of dipole excitations in two dimensions. This
      problem differs from the conventional Anderson localization due to the existence
      of long-range hops. We find that the critical wave functions of the dipoles
      always exist which manifest themselves by a scale independent diffusion constant.
      If the system is T invariant the states are critical for all values of the
      parameters. Otherwise, there can be a "metal-insulator" transition between this
      "ordinary" diffusion and the Levy flights (the diffusion constant logarithmically
      increasing with the scale). These results follow from the two-loop analysis of
      the modified nonlinear supermatrix sigma model.

PMID- 21902408
TI  - Time-dependent Gutzwiller theory for multiband Hubbard models.
AB  - Based on the variational Gutzwiller theory, we present a method for the
      computation of response functions for multiband Hubbard models with general local
      Coulomb interactions. The improvement over the conventional random-phase
      approximation is exemplified for an infinite-dimensional two-band Hubbard model
      where the incorporation of the local multiplet structure leads to a much larger
      sensitivity of ferromagnetism on the Hund coupling. Our method can be implemented
      into local-density approximation and Gutzwiller schemes and will therefore be an
      important tool for the computation of response functions for strongly correlated
      materials.

PMID- 21902409
TI  - Optical conductivity of the Holstein polaron.
AB  - The momentum average approximation is used to derive a new kind of
      nonperturbational analytical expression for the optical conductivity (OC) of a
      Holstein polaron at zero temperature. This provides insight into the shape of the
      OC, by linking it to the structure of the polaron's phonon cloud. Our method
      works in any dimension, properly enforces selection rules, can be systematically
      improved, and also generalizes to momentum-dependent couplings. Its accuracy is
      demonstrated by a comparison with the first detailed set of three-dimensional
      numerical OC results, obtained using the approximation-free diagrammatic Monte
      Carlo method.

PMID- 21902410
TI  - Critical Kondo destruction in a pseudogap Anderson model: scaling and
      relaxational dynamics.
AB  - We study the pseudogap Anderson model as a prototype system for critical Kondo
      destruction. We obtain finite-temperature (T) scaling functions near its quantum
      critical point, by using a continuous-time quantum Monte Carlo method and also
      considering a dynamical large-N limit. We are able to determine the behavior of
      the scaling functions in the typically difficult to access quantum-relaxational
      regime (homega<k(B)T) and conclude that the relaxation rates for both the spin
      and single-particle excitations are linear in temperature. We discuss the
      implications of these results for the quantum-critical phenomena in heavy-fermion
      metals.

PMID- 21902411
TI  - Macroscopic degeneracy and emergent frustration in a honeycomb lattice magnet.
AB  - Using a hybrid method based on fermionic diagonalization and classical Monte
      Carlo techniques, we investigate the interplay between itinerant and localized
      spins, with competing double- and superexchange interactions, on a honeycomb
      lattice. For moderate superexchange, a geometrically frustrated triangular
      lattice of hexagons forms spontaneously. For slightly larger superexchange a
      dimerized ground state is stable that has macroscopic degeneracy. The presence of
      these states on a nonfrustrated honeycomb lattice highlights novel phenomena in
      this itinerant electron system: emergent geometrical frustration and degeneracy
      related to a symmetry intermediate between local and global.

PMID- 21902412
TI  - Ultrafast transport of laser-excited spin-polarized carriers in Au/Fe/MgO(001).
AB  - Hot carrier-induced spin dynamics is analyzed in epitaxial Au/Fe/MgO(001) by a
      time domain approach. We excite a spin current pulse in Fe by 35 fs laser pulses.
      The transient spin polarization, which is probed at the Au surface by optical
      second harmonic generation, changes its sign after a few hundred femtoseconds.
      This is explained by a competition of ballistic and diffusive propagation
      considering energy-dependent hot carrier relaxation rates. In addition, we
      observe the decay of the spin polarization within 1 ps, which is associated with
      the hot carrier spin relaxation time in Au.

PMID- 21902413
TI  - Competition between weak localization and antilocalization in topological surface
      states.
AB  - A magnetoconductivity formula is presented for the surface states of a
      magnetically doped topological insulator. It reveals a competing effect of weak
      localization and weak antilocalization in quantum transport when an energy gap is
      opened at the Dirac point by magnetic doping. It is found that, while random
      magnetic scattering always drives the system from the symplectic to the unitary
      class, the gap could induce a crossover from weak antilocalization to weak
      localization, tunable by the Fermi energy or the gap. This crossover presents a
      unique feature characterizing the surface states of a topological insulator with
      the gap opened at the Dirac point in the quantum diffusion regime.

PMID- 21902414
TI  - Quantum spin Hall effect in silicene and two-dimensional germanium.
AB  - We investigate the spin-orbit opened energy gap and the band topology in recently
      synthesized silicene as well as two-dimensional low-buckled honeycomb structures
      of germanium using first-principles calculations. We demonstrate that silicene
      with topologically nontrivial electronic structures can realize the quantum spin
      Hall effect (QSHE) by exploiting adiabatic continuity and the direct calculation
      of the Z(2) topological invariant. We predict that the QSHE can be observed in an
      experimentally accessible low temperature regime in silicene with the spin-orbit
      band gap of 1.55 meV, much higher than that of graphene. Furthermore, we find
      that the gap will increase to 2.9 meV under certain pressure strain. Finally, we
      also study germanium with a similar low-buckled stable structure, and predict
      that spin-orbit coupling opens a band gap of 23.9 meV, much higher than the
      liquid nitrogen temperature.

PMID- 21902415
TI  - Dynamical resurrection of the visibility in a Mach-Zehnder interferometer.
AB  - We study a single-electron pulse injected into the chiral edge state of a quantum
      Hall device and subject it to a capacitive Coulomb interaction. We find that the
      scattered multiparticle state remains unentangled and hence can be created itself
      by a suitable classical voltage pulse. The application of an appropriate inverse
      pulse corrects for the shakeup due to the interaction and resurrects the original
      injected wave packet. We suggest an experiment with an asymmetric Mach-Zehnder
      interferometer where the application of such pulses manifests itself in an
      improved visibility.

PMID- 21902416
TI  - Inelastic electron tunneling spectroscopy of a single nuclear spin.
AB  - Detection of a single nuclear spin constitutes an outstanding problem in
      different fields of physics such as quantum computing or magnetic imaging. Here
      we show that the energy levels of a single nuclear spin can be measured by means
      of inelastic electron tunneling spectroscopy (IETS). We consider two different
      systems, a magnetic adatom probed with scanning tunneling microscopy and a single
      Bi dopant in a silicon nanotransistor. We find that the hyperfine coupling opens
      new transport channels which can be resolved at experimentally accessible
      temperatures. Our simulations evince that IETS yields information about the
      occupations of the nuclear spin states, paving the way towards transport-detected
      single nuclear spin resonance.

PMID- 21902417
TI  - Observation of the Kondo effect in a spin-3/2 hole quantum dot.
AB  - We report the observation of Kondo physics in a spin-3/2 hole quantum dot. The
      dot is formed close to pinch-off in a hole quantum wire defined in an undoped
      AlGaAs/GaAs heterostructure. We clearly observe two distinctive hallmarks of
      quantum dot Kondo physics. First, the Zeeman spin splitting of the zero-bias peak
      in the differential conductance is independent of the gate voltage. Second, this
      splitting is twice as large as the splitting for the lowest one-dimensional
      subband. We show that the Zeeman splitting of the zero-bias peak is highly
      anisotropic and attribute this to the strong spin-orbit interaction for holes in
      GaAs.

PMID- 21902418
TI  - Strong intramolecular electron-phonon coupling in the negatively charged aromatic
      superconductor picene.
AB  - Superconductivity was recently discovered in solid potassium-intercalated picene
      (K(3)22ph), in which the picene molecule becomes trianionic (22ph(3-)). In this
      Letter, we conduct a theory-based study of the superconductivity of 22ph(3-)
      within the framework of BCS theory. We estimate the density of states
      N(epsilon(F)) on the Fermi level to be 2.2 states per (eV molecule spin) by using
      the theoretical intramolecular electron-phonon coupling l(x) and the experimental
      superconducting transition temperature T(c) of 18 K. The theoretical value is
      consistent with the 1.2 states per (eV molecule spin) determined experimentally
      for K(3)22ph with T(c)=18 K, indicating the validity of our theoretical treatment
      and the electron-phonon mechanism for superconductivity. The predicted l(x),
      0.206 eV, for 22ph(3-) is larger than any value reported for organic
      superconductors, so picene may have the largest l(x) among the superconductors
      reported so far.

PMID- 21902419
TI  - Flow of a single magnetic vortex in a submicron-size superconducting Al disk
      controlled by radio-frequency currents.
AB  - We report the first observation of a single-vortex flow in a mesoscopic
      superconductor. A flow of a single vortex is successfully controlled by an rf
      current superimposed on a dc current, evidence of which is provided by voltage
      steps in current-voltage (I-V) characteristics. Irrespective of the number of
      vortices confined to the disk, we unambiguously observe that when a single vortex
      inside the disk is driven out of the disk, another vortex enters the disk
      similarly to two balls colliding in billiards: only one vortex passes through the
      Al disk at the same time in mesoscopic systems.

PMID- 21902420
TI  - Edge states of Sr2RuO4 detected by in-plane tunneling spectroscopy.
AB  - Tunneling spectroscopy has been performed on Sr(2)RuO(4) searching for the edge
      states peculiar to topological superconductivity. Conductance spectra exhibit
      broad humps with three types of peak shape: domelike peak, split peak, and two
      step peak. By comparing the experiments with predictions for unconventional
      superconductivity, these varieties are shown to originate from multiband chiral p
      wave symmetry with weak anisotropy of pair amplitude. The broad hump in the
      conductance spectrum is a direct manifestation of the edge state due to chiral p
      wave superconductivity.

PMID- 21902421
TI  - Persistent spin oscillations in a spin-orbit-coupled superconductor.
AB  - Quasi-two-dimensional superconductors with tunable spin-orbit coupling are very
      interesting systems with properties that are also potentially useful for
      applications. In this Letter we demonstrate that these systems exhibit undamped
      collective spin oscillations that can be excited by the application of a
      supercurrent. We propose to use these collective excitations to realize
      persistent spin oscillators operating in the frequency range of 10 GHz-1 THz.

PMID- 21902422
TI  - Noise correlations in three-terminal diffusive superconductor-normal-metal
      superconductor nanostructures.
AB  - We present measurements of current noise and cross correlations in three-terminal
      superconductor-normal-metal-superconductor (S-N-S) nanostructures that are
      potential solid-state entanglers thanks to Andreev reflections at the N-S
      interfaces. The noise-correlation measurements spanned from the regime where
      electron-electron interactions are relevant to the regime of incoherent multiple
      Andreev reflection. In the latter regime, negative cross correlations are
      observed in samples with closely spaced junctions.

PMID- 21902423
TI  - Kaleidoscope of exotic quantum phases in a frustrated XY model.
AB  - The existence of quantum spin liquids was first conjectured by Pomeranchuk some
      70 years ago, who argued that frustration in simple antiferromagnetic theories
      could result in a Fermi-liquid-like state for spinon excitations. Here we show
      that a simple quantum spin model on a honeycomb lattice hosts the long sought for
      Bose metal with a clearly identifiable Bose surface. The complete phase diagram
      of the model is determined via exact diagonalization and is shown to include four
      distinct phases separated by three quantum phase transitions.

PMID- 21902424
TI  - Resonant activation of a synthetic antiferromagnet.
AB  - The magnetic decay time of a synthetic antiferromagnet comprised of two closely
      spaced magnetic dipoles is measured in the presence of microwave excitation. The
      system is known to be highly stable with respect to switching between its two
      antiparallel ground states under quasistatic magnetic fields. We show that an
      order of magnitude lower field can switch the pair, provided the field is applied
      in resonance with the optical eigenmode of the collective spin dynamics in the
      system. We furthermore show that thermal agitation can play an essential role in
      spin-flop switching for resonant excitations of near- or subcritical amplitude.

PMID- 21902425
TI  - Non-Abelian spin liquid in a spin-one quantum magnet.
AB  - We study a time-reversal invariant non-Abelian spin-liquid state in an SU(2)
      symmetric spin S=1 quantum magnet on a triangular lattice. The spin liquid is
      obtained by quantum disordering a noncollinear nematic state. We show that such a
      spin liquid cannot be obtained by the standard projective construction for spin
      liquids. We also study the phase transition between the spin liquid and the
      noncollinear nematic state and show that it cannot be described within the Landau
      Ginzburg-Wilson paradigm.

PMID- 21902426
TI  - Effective field theory for the SO(n) bilinear-biquadratic spin chain.
AB  - We present a low-energy effective field theory to describe the SO(n) bilinear
      biquadratic spin chain. We start with n=6 and construct the effective theory by
      using six Majorana fermions. After determining various correlation functions, we
      characterize the phases and establish the relation between the effective theories
      for SO(6) and SO(5). Together with the known results for n=3 and 4, a reduction
      mechanism is proposed to understand the ground state for arbitrary SO(n). Also,
      we provide a generalization of the Lieb-Schultz-Mattis theorem for SO(n). The
      implications of our results for entanglement and correlation functions are
      discussed.

PMID- 21902427
TI  - Measurements of nanoscale domain wall flexing in a ferromagnetic thin film.
AB  - We use the high spatial sensitivity of the anomalous Hall effect in the
      ferromagnetic semiconductor Ga(1-x)Mn(x)As, combined with the magneto-optical
      Kerr effect, to probe the nanoscale elastic flexing behavior of a single magnetic
      domain wall in a ferromagnetic thin film. Our technique allows position sensitive
      characterization of the pinning site density, which we estimate to be ~10(14) cm(
      3). Analysis of single site depinning events and their temperature dependence
      yields estimates of pinning site forces (10 pN range) as well as the thermal
      deactivation energy. Our data provide evidence for a much higher intrinsic domain
      wall mobility for flexing than previously observed in optically probed MUm scale
      measurements.

PMID- 21902428
TI  - Selective probing of photoinduced charge and spin dynamics in the bulk and
      surface of a topological insulator.
AB  - Topological insulators possess completely different spin-orbit coupled bulk and
      surface electronic spectra that are each predicted to exhibit exotic responses to
      light. Here we report time-resolved fundamental and second harmonic optical pump
      probe measurements on the topological insulator Bi(2)Se(3) to independently
      measure its photoinduced charge and spin dynamics with bulk and surface
      selectivity. Our results show that a transient net spin density can be optically
      induced in both the bulk and surface, which may drive spin transport in
      topological insulators. By utilizing a novel rotational anisotropy analysis we
      are able to separately resolve the spin depolarization, intraband cooling, and
      interband recombination processes following photoexcitation, which reveal that
      spin and charge degrees of freedom relax on very different time scales owing to
      strong spin-orbit coupling.

PMID- 21902429
TI  - Common origin of the circular-dichroism pattern in angle-resolved photoemission
      spectroscopy of SrTiO3 and Cu(x)Bi2Se3.
AB  - Circular dichroism in the angular distribution of photoelectrons from SrTiO(3):Nb
      and Cu(x)Bi(2)Se(3) is investigated by 7-eV laser angle-resolved photoemission
      spectroscopy. In addition to the well-known node that occurs in the circular
      dichroism pattern when the incidence plane matches the mirror plane of the
      crystal, we show that another type of node occurs when the mirror plane of the
      crystal is vertical to the incidence plane and the electronic state is two
      dimensional. The flower-shaped circular dichroism patterns in the angular
      distribution occurring around the Fermi level of SrTiO(3):Nb and around the Dirac
      point of Cu(x)Bi(2)Se(3) are explained on equal footings. We point out that the
      penetration depth of the topological states of Cu(x)Bi(2)Se(3) depends on
      momentum.

PMID- 21902430
TI  - Structural description of the macroscopic piezo- and ferroelectric properties of
      lead zirconate titanate.
AB  - An in situ structural description of the origin of the ferroelectric properties
      as a function of the applied electric field E was obtained by synchrotron x-ray
      diffraction. A setup was used to average the effects of the preferred orientation
      induced by the strong piezoelectric strain and solve in situ the crystal
      structure as a function of the applied electric field. Hence, we were able to
      describe the microscopic origin of the macroscopic ferro- and piezoelectric
      properties of the most widely used ferroelectric material, lead zirconate
      titanate.

PMID- 21902431
TI  - Depletion versus deflection: how membrane bending can influence adhesion.
AB  - During depletion-driven vesicle adhesion, a stiff membrane's resistance to
      bending at fixed tension prevents contact angle equilibrium and vesicle spreading
      over an opposing vesicle, while more flexible vesicles partially engulf opposing
      vesicles. Estimates of the bending cost associated with the spreading contact
      line, relative to the adhesion energy, were consistent with the observed
      spreading or lack of spreading for the flexible and stiff membranes,
      respectively, and predicted a lag time sometimes preceding spreading.

PMID- 21902432
TI  - Microscopic theory of the tube confinement potential for liquids of topologically
      entangled rigid macromolecules.
AB  - We formulate and apply a microscopic self-consistent theory for the dynamic
      transverse confinement field in solutions of zero-excluded-volume rods based
      solely on topological entanglements. In agreement with the phenomenological tube
      model, an infinitely deep potential is predicted. However, strong anharmonicities
      are found to qualitatively soften localization, in quantitative agreement with
      experiments on heavily entangled biopolymer solutions. Predictions are also made
      for the effect of rod alignment on the transverse diffusion constant, tube
      diameter, and confinement force.

PMID- 21902433
TI  - Criticality and transmission of information in a swarm of cooperative units.
AB  - We show that the intelligence of a swarm of cooperative units (birds) emerges at
      criticality, as an effect of the joint action of frequent organizational
      collapses and of spatial correlation as extended as the flock size. The
      organizational collapses make the birds become independent of one another,
      thereby allowing the flock to follow the direction of the lookout birds. Long
      range correlation violates the principle of locality, making the lookout birds
      transmit information on either danger or resources with a time delay determined
      by the time distance between two consecutive collapses.

PMID- 21902434
TI  - Instabilities of monolayered epithelia: shape and structure of villi and crypts.
AB  - We study theoretically the shapes of a dividing epithelial monolayer of cells
      lying on top of an elastic stroma. The negative tension created by cell division
      provokes a buckling instability at a finite wave vector leading to the formation
      of periodic arrays of villi and crypts. The instability is similar to the
      buckling of a metallic plate under compression. We use the results to rationalize
      the various structures of the intestinal lining observed in vivo. Taking into
      account the coupling between cell division and local curvature, we obtain
      different patterns of villi and crypts, which could explain the different
      morphologies of the small intestine and the colon.

PMID- 21902435
TI  - Repulsive contact interactions make jammed particulate systems inherently
      nonharmonic.
AB  - Many jammed particulate systems, such as granular and colloidal materials,
      interact via repulsive contact forces. We find that these systems possess no
      harmonic regime in the large system limit (N->infinity) for all compressions
      Deltaphi studied, and at jamming onset Deltaphi->0 for all N. We perform fixed
      energy simulations following perturbations with amplitude delta along
      eigendirections of the dynamical matrix. The fluctuations abruptly spread to all
      modes for delta~delta(c) (where a single contact breaks) in contrast to linear
      and weakly nonlinear behavior. For delta > delta(c), all discrete modes disappear
      into a continuous frequency band. <delta(c)> scales with 1/N and Deltaphi, which
      limits harmonic behavior to only overcompressed systems. The density of
      vibrational modes deviates strongly from that predicted from the dynamical matrix
      when the system enters the nonharmonic regime, which significantly affects its
      mechanical and transport properties.

PMID- 21902436
TI  - Comment on "Influence of noise on force measurements".

PMID- 21902438
TI  - Comment on "Coexistence of Coulomb blockade and zero bias anomaly in a strongly
      coupled nanodot".

PMID- 21902440
TI  - Potential role of comanagement in "rescue" of surgical patients.
AB  - OBJECTIVES: To evaluate the effect of medical comanagement on outcomes of
      hospitalized surgical patients who had postoperative complications. STUDY DESIGN:
      Retrospective cohort study. METHODS: We used clinical and administrative data at
      a large urban hospital to conduct a cohort study of select surgical
      hospitalizations in 2008 and 2009. We identified patients who suffered
      postoperative complications using measures developed by the University Health
      System Consortium. Bivariate and multivariate regression analyses were used to
      determine the associations of postoperative comanagement with inpatient
      mortality, length of stay, and cost in surgical patients who had postoperative
      complications. RESULTS: From 21,728 total surgical hospitalizations, we
      identified 4040 hospitalizations involving primary procedures (mainly orthopedic
      and neurosurgical) that were associated with comanagement at least 25% of the
      time. After excluding cases with missing data, 501 hospitalizations (13.8%)
      involved a patient who suffered at least 1 postoperative complication. Patient
      characteristics between the comanaged (n = 297) and non-comanaged (n = 204)
      hospitalizations were well matched. Medical comanagement was associated with
      fewer in-hospital deaths (odds ratio 0.23, 95% confidence interval 0.05-0.99) in
      adjusted analysis. Comanaged compared with non-comanaged hospitalizations were
      associated with shorter stay (-2.6 days, P <.01) without significant differences
      in total cost. CONCLUSIONS: Comanagement of patients who had perioperative
      complications was associated with lower mortality, suggesting that comanagement
      may facilitate effective rescue among medically complex surgical patients.

PMID- 21902441
TI  - Disparities in antidepressant adherence in primary care: report from Israel.
AB  - OBJECTIVES: To evaluate patient and physician characteristics associated with the
      purchase of antidepressant medication for at least 6 months. STUDY DESIGN AND
      METHODS: Clalit Health Services is the largest managed care health fund in
      Israel, a country that uses a universal healthcare system. We randomly sampled
      30,000 primary care patients over the age of 22 years. Our analytic sample
      consisted of those 949 patients who did not purchase antidepressant medication
      during the last quarter of 2005 and purchased antidepressant medication at least
      once in 2006. We used multilevel analysis, with whether or not medication was
      purchased for at least 6 months as an indicator of adherence. Patient and
      physician characteristics were evaluated as potential predictors. RESULTS: Only
      23% of the sample was classified as adherent. Physician characteristics explained
      only a small portion of the variance in adherence and, as a result, were not
      included in multivariate analysis. Patients who did not have a somatic diagnosis,
      had a depression diagnosis, and were of higher socioeconomic status were more
      likely to be classified as adherent. Patients who purchased tricyclic
      antidepressants were less likely to be classified as adherent. CONCLUSIONS: The
      findings suggest that in a managed care setting, there is high uniformity among
      physicians. Although physician characteristics explain little of the variability
      associated with adherence, certain patient characteristics as determined by their
      physicians (eg, antidepressant drug class, psychiatric diagnosis) do play a role
      in adherence.

PMID- 21902442
TI  - Predictive model for emergency hospital admission and 6-month readmission.
AB  - OBJECTIVES: To study risk factors for and likelihood of unplanned hospital
      admission and readmission in persons aged >65 years in Catalonia, Spain. STUDY
      DESIGN: Retrospective cohort study. METHODS: We used data from clinical records
      of the primary care centers, pharmacy database, and hospital discharge records
      for persons aged >65 years registered in primary care centers of referral
      hospitals in the Baix Llobregat healthcare area. Unplanned hospital admission was
      defined as any unscheduled hospitalization in 2008; unplanned readmission was
      defined as any unscheduled admission occurring within 6 months after discharge
      date of index admission. Logistic regression analysis was used to identify
      predictors of unplanned hospital admission and readmission. RESULTS: The
      population included 28,430 individuals. Among them, 2103 (7%) experienced an
      unplanned admission and 365 (1.3%) an unplanned readmission. The readmission rate
      for the admitted population was 18.7%. The strongest predictive factor of
      unplanned admission was >2 admissions in the previous 2 years (odds ratio [OR]
      24.9, 95% confidence interval [CI] 16.0-38.7 for 2007; OR 15.6, 95% CI 8.6-28.0
      for 2006). Factors associated with unplanned readmission were aged >80 years (OR
      4.6, 95% CI 3.1-7.1) and >2 admissions during the previous year (OR 20.4, 95% CI
      14.1-29.5). The area under the receiver operating characteristics curve was 0.78
      for unplanned admission and 0.85 for unplanned readmission in the development
      sample and 0.76 and 0.81, respectively, in the validation sample. CONCLUSIONS:
      Aged persons and those who used more hospital services in previous years had a
      higher probability of hospital admission and readmission.

PMID- 21902443
TI  - Depression care following psychiatric hospitalization in the Veterans Health
      Administration.
AB  - OBJECTIVES: To assess quality of depression care during the high-risk period
      following a psychiatric hospitalization. STUDY DESIGN: Retrospective
      administrative data analysis. METHODS: Using Veterans Health Administration (VHA)
      administrative data, we assessed mental health follow-up within 7 and 30 days of
      psychiatric hospitalizations for major depression from 2004 to 2008. Adequate
      antidepressant medication coverage and number of psychotherapy visits were
      assessed within 90 days of discharge. Multivariable logistic regression was used
      to identify patient demographic and clinical characteristics associated with each
      quality indicator. RESULTS: Of the 45,587 patients discharged from a psychiatric
      inpatient stay with a diagnosis of major depressive disorder, 39.4% and 75.8%
      received an outpatient visit within 7 and 30 days of discharge, respectively;
      58.7% of patients received adequate antidepressant coverage (72 of 90 days) and
      12.9% received adequate psychotherapy encounters (8 visits). Receipt of
      outpatient mental health visits and of adequate psychotherapy were less likely
      among patients who were male, aged >35 or <65 years, had >3 major general medical
      comorbidities, lived >30 miles from a VHA clinic, or whose hospital length of
      stay was <7 days. Patients with comorbid substance use disorders were less likely
      to receive adequate antidepressant treatment. CONCLUSIONS: To optimize evidence
      based depression care after a psychiatric hospitalization, health systems might
      increase receipt of psychotherapy by considering potential barriers related to
      age, medical condition, and distance. Patients with comorbid substance use
      disorders or their providers may need additional services to support
      antidepressant treatment.

PMID- 21902444
TI  - Cost-offset analysis: bimatoprost versus other prostaglandin analogues in open
      angle glaucoma.
AB  - OBJECTIVES: To develop a cost-offset model from a US payer perspective comparing
      glaucomatous progression and costs among primary open-angle glaucoma (POAG)
      patients using bimatoprost, latanoprost, or travoprost. STUDY DESIGN: Cost-offset
      model. METHODS: A Markov cohort model was used to estimate glaucomatous
      progression for POAG patients over 7 years. The model assumed bimatoprost-treated
      patients had lower resulting intraocular pressure (IOP) (by 1 mm Hg) for all
      presenting IOP categories than latanoprost- or travoprost-treated patients.
      Patients with lower IOP were assumed to have lower probability of progression.
      Those that progressed were assumed to do so at a rate of -0.6 dB per year. Direct
      costs associated with mean deviation score categories were applied to each
      treatment cohort to calculate the expected 7-year costs of treating patients with
      each prostaglandin analogue (PGA). Literature was used to support assumptions. A
      budget impact analysis was conducted where all travoprost patients switched to
      generic latanoprost and where all bimatoprost patients switched to generic
      latanoprost. The base case market share was 22% bimatoprost, 23% travoprost, and
      55% latanoprost. RESULTS: Model results demonstrate that for a managed care plan
      with 9500 PGA-treated glaucoma patients, exclusive bimatoprost use would prevent
      progression in 136 additional individuals compared with exclusive travoprost or
      latanoprost treatment. Model results demonstrate that greater IOP reduction from
      bimatoprost is associated with increased cost savings compared with latanoprost
      or travoprost treatments. CONCLUSIONS: Model results demonstrate that greater IOP
      reduction from bimatoprost could reduce managed care spending.

PMID- 21902445
TI  - Inappropriate antibiotic prescribing in managed care subjects with influenza.
AB  - OBJECTIVES: To evaluate costs of inappropriate oral antibiotic prescribing in a
      managed care population with influenza. METHODS: This was a retrospective
      (January 1, 2005, through December 31, 2009) analysis of the US Impact National
      Benchmark Database. Patients with an influenza diagnosis (International
      Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] code
      487.xx) and continuous health plan enrollment for >12 months before and 1 month
      after the index influenza diagnosis date were included. We identified patients
      with an antibiotic prescription claim within 3 days before or 3 days after the
      index influenza diagnosis date. Patients were classified as having received
      appropriate antibiotic treatment if a secondary respiratory infection was
      observed within the 2-week postindex period or if there was a previous comorbid
      diagnosis of diabetes, congestive heart failure, chronic obstructive pulmonary
      disease, asthma, acute myocardial infarction, or sickle cell anemia as identified
      by ICD-9-CM codes. RESULTS: We identified 270,057 subjects with influenza (mean
      age, 31.6 years). Antibiotics were prescribed in 58,477 (21.65%) patients. Among
      patients receiving antibiotics, 99% did not have a follow-up diagnosis for a
      respiratory bacterial infection and 79% had neither a secondary infection nor
      evidence of a comorbidity (ie, received inappropriate antibiotic treatment).
      Based on a conservative annual seasonal influenza rate of 10%, we estimated that
      inappropriate antibiotic prescribing for influenza costs the United States
      approximately $211 million annually. CONCLUSIONS: Empiric antibiotics were
      inappropriately prescribed in a high percentage of influenza patients. This
      represents a significant financial burden to the US healthcare system and may
      contribute to increased antibiotic resistance.

PMID- 21902446
TI  - Compliance, persistence, and switching patterns for ACE inhibitors and ARBs.
AB  - OBJECTIVES: To investigate compliance, persistence, and switching patterns for
      angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers
      (ARBs). STUDY DESIGN: Drug-utilization analysis using a large prescription
      database. METHODS: Prescription data for more than 50,000 incident users of ACE
      inhibitors or ARBs were collected, cumulating close to 200,000 patient-years of
      medication use. Incidence, drug dosage, 1-year compliance, long-term persistence,
      and switching patterns were analyzed. The specific drugs investigated were
      captopril, enalapril, lisinopril, perindopril, ramipril, and fosinopril (ACE
      inhibitors), and losartan, valsartan, irbesartan, candesartan, and olmesartan
      (ARBs). Results were adjusted for age, sex, starting date, and comorbidities.
      RESULTS: The 1-year compliance (88.3% vs 88.3%, P = .996) and 3-year persistence
      (81.9% vs 82.4%, P = .197) rates were similar between ACE inhibitors and ARBs.
      Users of ACE inhibitors more often switched therapy (24.2% vs 13.1%, P <.001),
      primarily to an ARB. Variations in compliance, persistence, and switching
      behavior were detected between specific ACE inhibitors, but not between specific
      ARBs. CONCLUSIONS: Although residual confounding and indication bias cannot be
      ruled out, this study showed that compliance, persistence, and switching behavior
      varied between specific ACE inhibitors but not between specific ARBs. These
      results support prescribing of cheap generic ARBs as opposed to expensive ARBs.
      Apart from factors leading to therapy switches, compliance and persistence were
      similar between ACE inhibitors and ARBs.

PMID- 21902447
TI  - Mental illness and warfarin use in atrial fibrillation.
AB  - OBJECTIVES: To determine whether atrial fibrillation (AF) patients with mental
      health conditions (MHCs) were less likely than AF patients without MHCs to be
      prescribed warfarin and, if receiving warfarin, to maintain an International
      Normalized Ratio (INR) within the therapeutic range. STUDY DESIGN: Detailed chart
      review of AF patients using a Veterans Health Administration (VHA) facility in
      2003. METHODS: For a random sample of 296 AF patients, records identified
      clinician-diagnosed MHCs (independent variable) and AF-related care in 2003
      (dependent variables), receipt of warfarin, INR values below/above key
      thresholds, and time spent within the therapeutic range (2.0-3.0) or highly out
      of range. Differences between the MHC and comparison groups were examined using
      X2 tests and logistic regression controlling for age and comorbidity. RESULTS:
      Among warfarin-eligible AF patients (n = 246), 48.5% of those with MHCs versus
      28.9% of those without MHCs were not treated with warfarin (P = .004). Among
      those receiving warfarin and monitored in VHA, highly supratherapeutic INRs were
      more common in the MHC group; for example, 27.3% versus 1.6% had any INR >5.0 (P
      <.001). Differences persisted after adjusting for age and comorbidity.
      CONCLUSIONS: MHC patients with AF were less likely than those without MHC to have
      adequate management of their AF care. Interventions directed at AF patients with
      MHC may help to optimize their outcomes.

PMID- 21902448
TI  - Electronic health records, clinical decision support, and blood pressure control.
AB  - OBJECTIVES: Adding clinical decision support (CDS) to electronic health records
      (EHRs) is required under meaningful use legislation, but there has been little
      national data on effectiveness in improving clinical outcomes. We sought to
      determine whether EHRs with CDS improved blood pressure control in US primary
      care visits. STUDY DESIGN: We used a cross-sectional, nationally representative
      survey. METHODS: We examined adult visits to primary care physicians using the
      2007 and 2008 National Ambulatory Medical Care Survey (NAMCS). RESULTS: We found
      that patients had a mean age of 52 years, 34% were male, 15% had diabetes, and
      70% were white. Rates of blood pressure control were significantly higher in
      visits where both an EHR and CDS (79%) were used, compared with visits where
      physicians used neither tool (74%; P = .004). Blood pressure control rates
      remained higher after adjusting for potential confounders. In unadjusted
      analyses, mean systolic blood pressure was 2 mm Hg lower in visits with the use
      of both an EHR and CDS, compared with visits where physicians used neither tool
      (P = .03), and this difference remained significant after adjustment.
      CONCLUSIONS: The NAMCS shows that physician use of an EHR with CDS is associated
      with improved blood pressure control. These findings are important because small
      improvements in blood pressure control are associated with reductions in
      cardiovascular morbidity and mortality.

PMID- 21902449
TI  - Quality measurement of medication monitoring in the "meaningful use" era.
AB  - OBJECTIVES: While the 2011 implementation of "meaningful use" legislation for
      certified electronic health records (EHRs) promises to change quality reporting
      by overcoming data capture issues affecting quality measurement, the magnitude of
      this effect is unclear. We compared the measured quality of laboratory monitoring
      of Healthcare Effectiveness Data and Information Set (HEDIS) medications based on
      specifications that (1) include and exclude patients hospitalized in the
      measurement year and (2) use physician test orders and patient test completion.
      STUDY DESIGN: Cross-sectional study. METHODS: Among patients 18 years and older
      in a large multispecialty group practice utilizing a fully implemented EHR
      between January 1, 2008, and July 31, 2008, we measured the prevalence of
      ordering and completion of laboratory tests monitoring HEDIS medications
      (cardiovascular drugs [angiotensin-converting enzyme inhibitors or angiotensin
      receptor blockers, digoxin, and diuretics] and anticonvulsants [carbamazepine,
      phenobarbital, phenytoin, and valproic acid]). RESULTS: Measures excluding
      hospitalized patients were not statistically significantly different from
      measures including hospitalized patients, except for digoxin, but this difference
      was not clinically significant. The prevalence of appropriate monitoring based on
      test orders typically captured in the EHR was statistically significantly higher
      than the prevalence based on claims-based test completions for cardiovascular
      drugs. CONCLUSIONS: HEDIS quality metrics based on data typically collected from
      claims undermeasured quality of medication monitoring compared to EHR data. The
      HEDIS optional specification excluding hospitalized patients from the monitoring
      measure does not have a significant impact on reported quality. Integration of
      EHR data into quality measurement may significantly change some organizations'
      reported quality of care.

PMID- 21902450
TI  - Factors influencing healthy aging with multiple sclerosis: a qualitative study.
AB  - PURPOSE: The purpose of this study was to describe the factors influencing
      healthy aging from the perspective of the older person with multiple sclerosis
      (MS) in order to build curricula for MS self-management programs. METHOD: We
      sourced participants, older than 55 years with MS for more than 20 years, from a
      database of MS clinic and outpatient rehabilitation visits. Recruitment continued
      until data saturation was reached (n = 18). Semi-structured interviews explored
      perspectives on aging and health and lifestyle habits. Demographic, lifestyle and
      perceived health status information was also gathered. We analyzed the
      transcribed text for themes and theme relationships. RESULTS: Work and social
      engagement, effective and accessible health care, healthy lifestyle habits, and
      maintaining independence at home were found to be critical proximal factors for
      healthy aging. The presence of financial flexibility, social support, cognitive
      and mental health, and resilience provided a supporting foundation to these
      critical proximal factors. These factors comprised a two-tiered model of healthy
      aging with MS. CONCLUSIONS: This two-tiered conceptual model of health aging,
      based on the perspectives of older persons with MS, provides a potential
      framework for the development of MS self-management program curricula aimed at
      optimizing quality of life. Further empirical testing may validate its utility in
      predicting healthy aging with MS.

PMID- 21902451
TI  - The use of nonhuman primate models of HIV infection for the evaluation of
      antiviral strategies.
AB  - Several nonhuman primate models are used in HIV/AIDS research. In contrast to
      natural host models, infection of macaques with virulent simian immunodeficiency
      virus (SIV) isolates results in a disease (simian AIDS) that closely resembles
      HIV infection and AIDS. Although there is no perfect animal model, and each of
      the available models has its limitations, a carefully designed study allows
      experimental approaches that are not feasible in humans, but that can provide
      better insights in disease pathogenesis and proof-of-concept of novel
      intervention strategies. In the early years of the HIV pandemic, nonhuman primate
      models played a minor role in the development of antiviral strategies. Since
      then, a better understanding of the disease and the development of better
      compounds and assays to monitor antiviral effects have increased the usefulness
      and relevance of these animal models in the preclinical development of HIV
      vaccines, microbicides, and antiretroviral drugs. Several strategies that were
      first discovered to have efficacy in nonhuman primate models are now increasingly
      used in humans. Recent trends include the use of nonhuman primate models to
      explore strategies that could reduce viral reservoirs and, ultimately, attempt to
      cure infection. Ongoing comparison of results obtained in nonhuman primate models
      with those observed in human studies will lead to further validation and
      improvement of these animal models so they can continue to advance our scientific
      knowledge and guide clinical trials.

PMID- 21902452
TI  - Peroxiredoxin 3 is a key molecule regulating adipocyte oxidative stress,
      mitochondrial biogenesis, and adipokine expression.
AB  - AIMS: Increased oxidative stress and mitochondrial dysfunction in obese
      adipocytes contribute to adipokine dysregulation, inflammation, and insulin
      resistance. RESULTS: Through an advanced proteomic analysis, we found that
      peroxiredoxin 3 (Prx3), a thioredoxin-dependent mitochondrial peroxidase, is
      highly expressed in 3T3-L1 adipocytes compared to preadipocytes. Interestingly,
      in obese db/db mice and human subjects, adipose Prx3 levels were significantly
      decreased, indicating its association with obesity. We therefore employed Prx3
      knockout (KO) mice and transfected 3T3-L1 cells to examine the role of endogenous
      Prx3 in adipocyte metabolism. Prx3 KO mice had increased fat mass compared to
      wild-type due to adipocyte hypertrophy. Increased adipogenic transcription
      factors and lipogenic gene expression during differentiation of adipose tissue
      derived stem cells from Prx3-deficient mice confirmed that these adipocytes are
      likely to accumulate fat. Mitochondrial protein carbonylation in Prx3 KO adipose
      tissue and mitochondrial superoxide level in Prx3 knockdown 3T3-L1 cells were
      increased showing aberrant regulation of oxidative stress. Proteomic analysis and
      gene expression analysis of Prx3 KO mice adipocytes also showed defect in
      mitochondria biogenesis along with enzymes involved in glucose/lipid metabolism
      and oxidative phosphorylation. In addition, expression level of adiponectin was
      downregulated and plasminogen activator inhibitor-1 was upregulated in Prx3 KO
      adipocytes. Impaired glucose tolerance and insulin resistance further implied
      metabolic dysregulation in Prx3 KO mice. INNOVATION AND CONCLUSION: These data
      suggest that endogenous Prx3 may play an essential role in maintaining normal
      characteristics of adipocytes and that defect in Prx3 alters mitochondrial redox
      state and function, and adipokine expression in adipocytes leading to metabolic
      alteration.

PMID- 21902453
TI  - Peroxiredoxin-2 upregulated by NF-kappaB attenuates oxidative stress during the
      differentiation of muscle-derived C2C12 cells.
AB  - AIM: Many studies have reported that the generation of reactive oxygen species
      (ROS) increases during the differentiation of muscle-derived C2C12 cells.
      Peroxiredoxin-2 (Prx-2) is an abundant mammalian enzyme that protects against
      oxidative stress. However, the role of Prx-2 in muscle differentiation has not
      been investigated. RESULTS: In this study, we demonstrated that Prx-2 expression
      increases during muscle differentiation and regeneration in response to exogenous
      H(2)O(2). This increase occurs only in myoblast cell lines because no increase in
      Prx-2 expression was observed in the NIH3T3, MEF, Chang, or HEK293 cell lines.
      The antioxidants, N-acetyl L-cysteine (NAC) and 4,5-dihydroxy-1,3
      benzenedisulfonic acid (Tiron), both suppressed myogenesis and Prx-2 expression.
      Moreover, Prx-2 was upregulated at the transcriptional level by NF-kappaB during
      the differentiation of muscle-derived C2C12 cells. We also found that inhibition
      of phosphatidylinositol 3-kinase (PI3K) blocks NF-kappaB activation and
      suppresses Prx-2 expression. Interestingly, Prx-2 knockdown increased the
      expression levels of other antioxidant enzymes, including all of the other Prx
      family member, thioredoxin-1 (Trx-1) and catalase, but also enhanced the
      accumulation of endogenous ROS during muscle differentiation. INNOVATION: In this
      study, we demonstrated for the first time that Prx-2 is unregulated during the
      muscle differentiation and regeneration. CONCLUSION: Prx-2 is upregulated via the
      PI3K/NF-kappaB pathway and attenuates oxidative stress during muscle
      differentiation and regeneration.

PMID- 21902454
TI  - Comparative genomics of thiol oxidoreductases reveals widespread and essential
      functions of thiol-based redox control of cellular processes.
AB  - AIMS: Redox regulation of cellular processes is an important mechanism that
      operates in organisms from bacteria to mammals. Much of the redox control is
      provided by thiol oxidoreductases: proteins that employ cysteine residues for
      redox catalysis. We wanted to identify thiol oxidoreductases on a genome-wide
      scale and use this information to obtain insights into the general principles of
      thiol-based redox control. RESULTS: Thiol oxidoreductases were identified by
      three independent methods that took advantage of the occurrence of selenocysteine
      homologs of these proteins and functional linkages among thiol oxidoreductases
      revealed by comparative genomics. Based on these searches, we describe
      thioredoxomes, which are sets of thiol oxidoreductases in organisms. Their
      analyses revealed that these proteins are present in all living organisms,
      generally account for 0.5%-1% of the proteome and that their use correlates with
      proteome size, distinguishing these proteins from those involved in core
      metabolic functions. We further describe thioredoxomes of Saccharomyces
      cerevisiae and humans, including proteins which have not been characterized
      previously. Thiol oxidoreductases occur in various cellular compartments and are
      enriched in the endoplasmic reticulum and cytosol. INNOVATION: We developed
      bioinformatics methods and used them to characterize thioredoxomes on a genome
      wide scale, which in turn revealed properties of thioredoxomes. CONCLUSION: These
      data provide information about organization and properties of thiol-based redox
      control, whose use is increased with the increase in complexity of organisms. Our
      data also show an essential combined function of a set of thiol oxidoreductases,
      and of thiol-based redox regulation in general, in all living organisms.

PMID- 21902456
TI  - Strategic role for mitochondria in Alzheimer's disease and cancer.
AB  - SIGNIFICANCE: Detailed knowledge about cell death and cell survival mechanisms
      and how these pathways are impaired in neurodegenerative disorders and cancer
      forms the basis for future drug development for these diseases that affect
      millions of people around the world. RECENT ADVANCES: In neurodegenerative
      disorders such as Alzheimer's disease (AD), cell death pathways are
      inappropriately activated, resulting in neuronal cell death. In contrast, cancer
      cells develop resistance to apoptosis by regulating anti-apoptotic proteins
      signaling via mitochondria. Mounting evidence shows that mitochondrial function
      is central in both cancer and AD. Cancer cells typically shut down oxidative
      phosphorylation (OXPHOS) in mitochondria and switch to glycolysis for ATP
      production, making them resistant to hypoxia. In AD, for example, amyloid-beta
      peptide (Abeta) and reactive oxygen species impair mitochondrial function.
      Neurons therefore also switch to glycolysis to maintain ATP production and to
      produce molecules involved in antioxidant metabolism in an attempt to survive.
      CRITICAL ISSUES: One critical difference between cancer cells and neurons is that
      cancer cells can survive without OXPHOS, while neurons are dependent on OXPHOS
      for long-term survival. FUTURE DIRECTIONS: This review will focus on these
      abnormalities of mitochondrial function shared in AD and cancer and discuss the
      potential mechanisms underlying links that may be key steps in the development of
      therapeutic strategies.

PMID- 21902455
TI  - Novel bacterial gas sensor proteins with transition metal-containing prosthetic
      groups as active sites.
AB  - SIGNIFICANCE: Gas molecules function as signaling molecules in many biological
      regulatory systems responsible for transcription, chemotaxis, and other complex
      physiological processes. Gas sensor proteins play a crucial role in regulating
      such biological systems in response to gas molecules. RECENT ADVANCES: New sensor
      proteins that sense oxygen or nitric oxide have recently been found, and they
      have been characterized by X-ray crystallographic and/or spectroscopic analysis.
      It has become clear that the interaction between a prosthetic group and gas
      molecules triggers dynamic structural changes in the protein backbone when a gas
      sensor protein senses gas molecules. Gas sensor proteins employ novel mechanisms
      to trigger conformational changes in the presence of a gas. CRITICAL ISSUES: In
      gas sensor proteins that have iron-sulfur clusters as active sites, the iron
      sulfur clusters undergo structural changes, which trigger a conformational
      change. Heme-based gas sensor proteins reconstruct hydrogen-bonding networks
      around the heme and heme-bound ligand. FUTURE DIRECTION: Gas sensor proteins have
      two functional states, on and off, which are active and inactive, respectively,
      for subsequent signal transduction in response to their physiological effector
      molecules. To fully understand the structure-function relationships of gas sensor
      proteins, it is vital to perform X-ray crystal structure analyses of full-length
      proteins in both the on and off states.

PMID- 21902457
TI  - Post-injury personality in the prediction of outcome following severe acquired
      brain injury.
AB  - PRIMARY OBJECTIVE: The aim of the study was to examine the utility of five
      measures of non-cognitive neurobehavioural (NCNB) changes that often occur
      following acquired brain injury, in predicting outcome (measured in terms of
      participation and social adaptation) at 1-year follow-up. RESEARCH DESIGN: The
      study employed a longitudinal, correlational design. METHODS AND PROCEDURES:
      Multiple regression was employed to investigate the value of five new NCNB
      measures of social perception, emotional regulation, motivation, impulsivity and
      disinhibition in the prediction of outcome as measured by the Mayo-Portland
      Adaptability Inventory (MPAI). MAIN OUTCOMES AND RESULTS: Two NCNB measures
      (motivation and emotional regulation) were found to significantly predict outcome
      at 1-year follow-up, accounting for 53% of the variance in MPAI total scores.
      CONCLUSIONS: These measures provide a method of quantifying the extent of NCNB
      changes following brain injury. The predictive value of the measures indicates
      that they may represent a useful tool which could aid clinicians in identifying
      early-on those whose symptoms are likely to persist and who may require ongoing
      intervention. This could facilitate the planning of rehabilitation programmes.

PMID- 21902458
TI  - The party planning task: a useful tool in the functional assessment of planning
      skills in adolescents with TBI.
AB  - PRIMARY OBJECTIVE: To use two case studies to illustrate the clinical utility of
      the Party Planning Task (PPT), a non-standardized executive function assessment.
      BACKGROUND: Executive dysfunction is common following paediatric TBI. However,
      known difficulties with standardized assessment of executive functions (EF)
      exist. In particular, the ecologic validity of standardized measures has been
      questioned. The PPT is an ecological measure of EF and this paper reports
      findings from its use with two adolescents. Descriptive and observational data of
      their planning and organizational skills is presented. Each adolescent completed
      the PPT followed by a stimulated recall task. This was audio recorded and
      transcribed for content analysis. MAIN OUTCOMES AND RESULTS: Both participants
      scored within the normative range for severe TBI on the PPT, with each making
      greater than eight errors. Qualitative results indicated differences between
      participants in efficiency of task completion and transfer of strategies from
      previous intervention. CONCLUSIONS AND IMPLICATIONS: The PPT was shown to be a
      useful tool in the functional assessment of EF for these two adolescents. The
      opportunity for clinicians to observe the process taken by participants to
      complete the task provides valuable data, useful in determining strategy
      transferability as well as assisting in determining future intervention goals.

PMID- 21902459
TI  - Script generation and the dysexecutive syndrome in patients with brain injury.
AB  - OBJECTIVE: The authors investigated whether patients with brain injury suffering
      from dysexecutive symptoms had difficulties with script generation. METHOD: Forty
      eight patients with brain injury of various etiology with complaints of executive
      dysfunctioning and deficient scores on executive tests were included in this
      study. They were compared with 99 healthy control subjects in a script-generation
      task. Participants were asked to describe how they would perform eight everyday
      activities. The script items were manipulated so that they varied in structure
      (open-ended vs. closed) and in frequency of performing (high vs. low). RESULTS:
      Patients and control subjects evoked an equal number of actions, but
      patientsproduced significantly more irrelevant actions and made significantly
      more perseverative errors. Their most pronounced problems were found in open
      ended and low-frequency scripts. CONCLUSION: This investigation shows that not
      only patients with prefrontal damage are impaired in script generation. The
      consequences for treatment are discussed.

PMID- 21902460
TI  - The prevalence of patients in a vegetative state and minimally conscious state in
      nursing homes in Austria.
AB  - PRIMARY OBJECTIVE: To explore the epidemiology of patients in a Vegetative State
      (VS) and Minimally Conscious State (MCS) that are cared for in long-term care
      facilities in Austria. The study was inspired by increasing evidence that the
      cognitive abilities of minimal behavioural patients with disorders of
      consciousness may be under-rated. RESEARCH DESIGN: Since an unequivocal
      diagnostic code with which to follow-up these long-term patients after the acute
      event does not exist, a telephone survey was conducted. METHODS AND PROCEDURES: A
      three-step telephone- and questionnaire-based inquiry was conducted between 2007
      and 2009. MAIN OUTCOMES AND RESULTS: One hundred and fourteen out of 889 long
      term care facilities and nursing homes cared for 269 patients in a VS and 120
      patients in a MCS, indicating a prevalence of 3.36 patients per 100 000 for VS
      and 1.5 per 100 000 for MCS in long-term care facilities. CONCLUSIONS: The
      results are discussed in the light of differences in prevalence in other Western
      countries. Future studies should concentrate on these long-term patients since
      the results have implications regarding how to organize appropriate
      neurorehabilitative care that meets the needs of such patients.

PMID- 21902461
TI  - Neuronal structural protein polymorphism and concussion in college athletes.
AB  - OBJECTIVE: To examine the association between a neuronal structural protein
      polymorphism and the frequency and severity of concussions in college athletes.
      METHODS: Forty-eight athletes with previous self-reported history of a concussion
      were matched with 48 controls that did not report a history of concussion. Each
      group was genotyped for neurofilament heavy (NEFH) polymorphism rs#165602 in this
      retrospective case-control study. RESULTS: There was no significant association
      (chi(2 )= 0.487, p = 0.485) between carrying the NEFH rare allele and a history
      of one or more concussions due to small effect sizes. A Fisher's exact test
      revealed no significant association (p = 1.00, phi = -0.03) between the presence
      of NEFH rare allele and a history of multiple concussions. The independent t
      tests revealed no significant differences in duration of signs and symptoms (t =
      1.41, p = 0.17, d = 0.48) or return to play (t = 0.23, p = 0.82, d = 0.08)
      between NEFH rare allele carrier and non-carriers. CONCLUSIONS: Among college
      athletes, carrying the rare allele assessed may not influence an athlete's
      susceptibility to sustaining a concussion or return to play duration following a
      concussion.

PMID- 21902462
TI  - Goal-directed outpatient rehabilitation following TBI: a pilot study of programme
      effectiveness and comparison of outcomes in home and day hospital settings.
AB  - PRIMARY OBJECTIVE: To determine (i) the effectiveness of a goal-directed,
      environment-focused occupational therapy intervention and (ii) to compare
      rehabilitation gains across a day hospital (outpatient) setting and home setting.
      RESEARCH DESIGN: Repeated measures cross-over design with pre-post test measures
      and a baseline control period, random allocation to a treatment setting sequence
      and an independent outcome assessor who was blinded to treatment sequence.
      METHODS AND PROCEDURES: Descriptive and non-parametric comparative analyses
      employed. Fourteen participants with severe traumatic brain injury completed a 12
      week outpatient occupational therapy programme. The programme was directed by the
      participant's chosen goals, which were established using a client-centred,
      structured, goal-planning process. Outcome measures included Goal attainment
      scaling, the Canadian Occupational Performance Measure, the Sydney Psychosocial
      Reintegration Scale, the Mayo-Portland Adaptability Index, the Craig Hospital
      Inventory of Environmental Factors and self-rated satisfaction with therapy. MAIN
      OUTCOMES AND RESULTS: The therapy programme resulted in significant improvements
      in goal attainment, occupational performance, psychosocial reintegration and
      ability and adjustment levels, compared with baseline. Differences in gains made
      in home vs day hospital settings were not statistically significant, with the
      exception of higher levels of patient satisfaction with therapy at home.
      CONCLUSIONS: To assist further with decision-making about where to conduct
      therapy, further research is needed to compare the outcomes and determine the
      cost effectiveness of therapy at home and in day hospital settings.

PMID- 21902463
TI  - Pheochromocytoma presented with vertebral artery dissection.
AB  - BACKGROUND: Pheochromocytoma may rarely cause arterial dissection. Here the
      authors report a patient with pheochromocytoma complicated with vertebral artery
      dissection (VAD) and stroke. CASE HISTORY: A 48-year-old man presented with
      probable diagnosis of myocardial infarction. Following premedication with
      methylprednisolone for coronary artery angiography, he had unstable hypertension.
      Three days later, he had right cerebellar and left occipital lobe infarction in
      association with VAD. Urinary cathecolamines and MR scan of the abdomen suggested
      a diagnosis of phaeochromocytoma, which was later histopathologically confirmed.
      CONCLUSION: This case is interesting in that there is no previous report of the
      combination of pheochromocytoma, VAD, and stroke. Awareness of the atypical
      clinical presentations of this tumor is important for definitive treatment.

PMID- 21902464
TI  - The evaluation of ectopic bone formation induced by delivery systems for bone
      morphogenetic protein-9 or its derived peptide.
AB  - We have earlier shown that a peptide derived from the bone morphogenetic protein
      9 (pBMP-9) stimulates mouse preosteoblasts MC3T3-E1 differentiation in vitro.
      Here, we evaluated the effects of two delivery systems (DSs) for pBMP-9, one
      based on collagen and the other on chitosan. The release kinetics of BMP-9 (used
      as control) and pBMP-9 from these DSs were first determined in vitro by using
      enzyme-linked immunosorbent assay and high performance liquid chromatography
      assays, respectively. Micro-computerized tomography and histological analysis
      were then performed to study in vivo the ectopic ossification induced by both DSs
      containing these molecules in C57BL/6 mouse quadriceps. We found that collagen DS
      released in vitro about 35% of its BMP-9 within 1 h, whereas chitosan DS released
      80%. The pBMP-9 was released from both DSs more slowly for up to 10 days. These
      release kinetics seemed to fit the Korsmeyer-Peppas model. Only chitosan DS
      containing BMP-9 induced strong bone formation in all mice quadriceps within 24
      days. All mice quadriceps treated by pBMP-9 trapped in this DS also favored bone
      structures that started to mineralize. However, pBMP-9 in collagen DS failed to
      promote ectopic ossification within 24 days in vivo. This study highlights the
      importance to optimize carrier, thus improving the efficiency of pBMP-9 in vivo.

PMID- 21902465
TI  - Three-dimensional cell grafting enhances the angiogenic efficacy of human
      umbilical vein endothelial cells.
AB  - Despite the great potential of cell therapy for ischemic disease, poor cell
      survival after engraftment in ischemic tissue limits its efficacy. Here we tested
      a hypothesis that three-dimensionally grafted human umbilical vein endothelial
      cell (HUVEC) spheroids would exhibit improved angiogenic efficacy following
      transplantation into mouse ischemic limbs compared with HUVECs prepared by
      conventional two-dimensional monolayer culture. One day after surgical induction
      of hindlimb ischemia in athymic mice, HUVECs cultured in monolayer or HUVEC
      spheroids were transplanted intramuscularly into ischemic limbs. Four weeks after
      the treatment, in the spheroid HUVEC transplantation group, we observed increased
      hypoxia-inducible factor-1alpha expression, decreased apoptosis, and increased
      HUVEC survival in the ischemic tissue compared with the monolayer HUVEC
      transplantation group. Transplantation of HUVEC spheroids also resulted in
      enhanced and prolonged secretion of paracrine factors as well as enhanced
      expression of factors involved in the recruitment of circulating angiogenic
      progenitor cells. In summary, transplantation of HUVECs as spheroids enhanced
      cell survival, increased paracrine factor secretion, and showed a potential as a
      therapeutic method to treat ischemic tissue damages by promoting angiogenesis.

PMID- 21902466
TI  - Insulin-like growth factor 2 promotes osteogenic cell differentiation in the
      parthenogenetic murine embryonic stem cells.
AB  - Embryonic stem cells (ESCs) are pluripotent and can differentiate into all
      somatic cell types. ESCs are an alternative solution to hard tissue regeneration
      and skeletal tissue repair to treat bone diseases and defects using regenerative
      strategies. Parthenogenetic ESCs (PESCs) may be a useful alternative stem cell
      source for tissue repair and regeneration. The defects in full-term development
      of this cell type enable researchers to avoid the ethical concerns related to ESC
      research. Moreover, in female patients, if the PESCs are derived from oocytes,
      then they will have that patient's genetic information. Here, we present data
      demonstrating that osteogenic differentiation of PESCs can be promoted by insulin
      like growth factor 2 (IGF2). PESCs were plated onto Petri dishes with ESC culture
      medium supplemented with or without IGF2, followed by culturing of the cells for
      1 week. PESCs formed floating aggregates called embryoid bodies (EBs). An
      osteogenic lineage was induced from the EBs by incubating them in medium
      containing serum, ascorbic acid, beta-glycerophosphate, and retionic acid, with
      or without IGF2, for 20 days. Gene expression of specific osteoblastic markers
      such as osteocalcin, osteopontin, osteonectin, bone sialoprotein, collagen type
      I, alkaline phosphatase, and Runx2 (Cbfa-I) was analyzed by real-time polymerase
      chain reaction. The expression level of osteocalcin, osteopontin, osteonectin,
      and alkaline phosphatase was twofold higher in IGF2-treated PESC derivatives than
      IGF2-naive PESC derivatives. In vivo experiments were also performed using a
      critical-sized calvarial defect mouse model. Ten weeks after cell
      transplantation, more bone tissue regeneration was observed in the IGF2-treated
      PESC transplantation group than in IGF2-naive PESC transplantation group. Both
      our in vitro and in vivo data indicate that IGF2 induces osteogenic
      differentiation of PESCs. Addition of IGF2 may reactivate imprinting genes in
      PESCs that are only expressed in the paternal genome and are normally silent in
      PESCs. Our findings provide insights into the mechanisms of skeletal tissue
      repair and the imprinting mechanisms active in stem cells.

PMID- 21902468
TI  - Adipogenesis of human adipose-derived stem cells within three-dimensional hollow
      fiber-based bioreactors.
AB  - To further differentiate adipose-derived stem cells (ASCs) into mature adipocytes
      and create three-dimensional (3D) adipose tissue in vitro, we applied
      multicompartment hollow fiber-based bioreactor technology with decentral mass
      exchange for more physiological substrate gradients and integral oxygenation. We
      hypothesize that a dynamic 3D perfusion in such a bioreactor will result in
      longer-term culture of human adipocytes in vitro, thus providing metabolically
      active tissue serving as a diagnostic model for screening drugs to treat
      diabetes. ASCs were isolated from discarded human abdominal subcutaneous adipose
      tissue and then inoculated into dynamic 3D culture bioreactors to undergo
      adipogenic differentiation. Insulin-stimulated glucose uptake from the medium was
      assessed with and without TNF-alpha. 3D adipose tissue was generated in the 3D
      bioreactors. Immunohistochemical staining indicated that 3D-bioreactor culture
      displayed multiple mature adipocyte markers with more unilocular morphologies as
      compared with two-dimensional (2D) cultures. Results of real-time polymerase
      chain reaction showed 3D-bioreactor treatment had more efficient differentiation
      in fatty acid-binding protein 4 expression. Repeated insulin stimulation resulted
      in increased glucose uptake, with a return to baseline between testing.
      Importantly, TNF-alpha inhibited glucose uptake, an indication of the metabolic
      activity of the tissue. 3D bioreactors allow more mature adipocyte
      differentiation of ASCs compared with traditional 2D culture and generate adipose
      tissue in vitro for up to 2 months. Reproducible metabolic activity of the
      adipose tissue in the bioreactor was demonstrated, which is potentially useful
      for drug discovery. We present here, to the best of our knowledge for the first
      time, the development of a coherent 3D high density fat-like tissue consisting of
      unilocular structure from primary adipose stem cells in vitro.

PMID- 21902467
TI  - Response of human engineered cartilage based on articular or nasal chondrocytes
      to interleukin-1beta and low oxygen.
AB  - Previous studies showed that human nasal chondrocytes (HNC) exhibit higher
      proliferation and chondrogenic capacity as compared to human articular
      chondrocytes (HAC). To consider HNC as a relevant alternative cell source for the
      repair of articular cartilage defects it is necessary to test how these cells
      react when exposed to environmental factors typical of an injured joint. We thus
      aimed this study at investigating the responses of HNC and HAC to exposure to
      interleukin (IL)-1beta and low oxygen. For this purpose HAC and HNC harvested
      from the same donors (N=5) were expanded in vitro and then cultured in pellets or
      collagen-based scaffolds at standard (19%) or low oxygen (5%) conditions.
      Resulting tissues were analyzed after a short (3 days) exposure to IL-1beta,
      mimicking the initially inflammatory implantation site, or following a recovery
      time (1 or 2 weeks for pellets and scaffolds, respectively). After IL-1beta
      treatment, constructs generated by both HAC and HNC displayed a transient loss of
      GAG (up to 21.8% and 36.8%, respectively) and, consistently, an increased
      production of metalloproteases (MMP)-1 and -13. Collagen type II and the cryptic
      fragment of aggrecan (DIPEN), both evaluated immunohistochemically, displayed a
      trend consistent with GAG and MMPs production. HNC-based constructs exhibited a
      more efficient recovery upon IL-1beta withdrawal, resulting in a higher
      accumulation of GAG (up to 2.6-fold) compared to the corresponding HAC-based
      tissues. On the other hand, HAC displayed a positive response to low oxygen
      culture, while HNC were only slightly affected by oxygen percentage.
      Collectively, under the conditions tested mimicking the postsurgery articular
      environment, HNC retained a tissue-forming capacity, similar or even better than
      HAC. These results represent a step forward in validating HNC as a cell source
      for cartilage tissue engineering strategies.

PMID- 21902469
TI  - Optimizing an intermittent stretch paradigm using ERK1/2 phosphorylation results
      in increased collagen synthesis in engineered ligaments.
AB  - Dynamic mechanical input is believed to play a critical role in the development
      of functional musculoskeletal tissues. To study this phenomenon, cyclic uniaxial
      mechanical stretch was applied to engineered ligaments using a custom-built
      bioreactor and the effects of different stretch frequency, amplitude, and
      duration were determined. Stretch acutely increased the phosphorylation of p38
      (3.5+/-0.74-fold), S6K1 (3.9+/-0.19-fold), and ERK1/2 (2.45+/-0.32-fold). The
      phosphorylation of ERK1/2 was dependent on time, rather than on frequency or
      amplitude, within these constructs. ERK1/2 phosphorylation was similar following
      stretch at frequencies from 0.1 to 1 Hz and amplitudes from 2.5% to 15%, whereas
      phosphorylation reached maximal levels at 10 min of stretch and returned toward
      basal within 60 min of stretch. Following a single 10-min bout of cyclic stretch,
      the cells remained refractory to a second stretch for up to 6 h. Using the
      phosphorylation of ERK1/2 as a guide, the optimum stretch paradigm was
      hypothesized to be 10 min of stretch at 2.5% of resting length repeated every 6
      h. Consistent with this hypothesis, 7 days of stretch using this optimized
      intermittent stretch program increased the collagen content of the grafts more
      than a continuous stretch program (CTL=3.1%+/-0.44%; CONT=4.8%+/-0.30%; and
      INT=5.9%+/-0.56%). These results suggest that short infrequent bouts of loading
      are optimal for improving engineered tendon and ligament physiology.

PMID- 21902471
TI  - Nucleosides 7(9): synthesis, structure, and biological activity of new 6
      arylidenamino-2-thio- and 2-benzylthiopyrimidine N-nucleosides.
AB  - The condensation of 6-amino-2-thioxo-2,3-dihydro-1H-pyrimidine-4-one [compound
      (1)] with aromatic aldehydes (2) afforded azomethine derivatives (3). The formed
      azomethines underwent glycosidation with alpha-acetobromoglucose (4) to form the
      corresponding pyrimidine N-glycosides (6) and not S-glycosides (5). The
      interaction of (3) with 1-O-acetyl-2, 3, 5-tri-O-benzoyl-beta-D-ribofuranose (8)
      afforded the corresponding pyrimidine N-riboside (10) and not S-riboside (9).
      Deacetylation and debenzoylation of each of (6) and (10) by using methanolic
      sodium methoxide afforded the corresponding free N-nucleosides (7) and (11),
      respectively. Next, the reaction of 2-benzylthio-6-benzylidenaminouracil (13)
      with (4) and (8) did not yield the corresponding protected N-nucleosides (14) and
      (17), whereas it afforded (15) and (18), respectively. The latter compounds (15)
      and (18) were stirred in methanolic sodium methoxide to yield the corresponding
      free N-nucleosides (16) and (19), respectively. The structures of products have
      been elucidated and reported and also some of the products were screened for
      their antimicrobial activity. Graphical Abstract:

PMID- 21902470
TI  - Efficient preparation of alkali-insoluble (1 -> 3)-beta-D-glucan.
AB  - The alkali-insoluble (1 -> 3)-beta-d-glucan was prepared by alkaline-acid method
      and followed deproteinization by alkaline method using yeast cell wall as the
      starting material. The deproteinized product was characterized by infrared (IR)
      spectroscopy, and the polysaccharide components were analysed by paper
      chromatography. It indicated that the alkaline-acid method was an ideal way for
      preparing (1 -> 3)-beta-d-glucan. The obtained glucan had high purity and good
      yield.

PMID- 21902472
TI  - Enzymatic probing analysis of an engineered riboswitch reveals multiple off
      conformations.
AB  - We investigated the gene regulatory mechanism of a previously engineered
      riboswitch +thiMN(15)#19 that turns on gene expression in response to thiamine
      pyrophosphate (TPP). In vitro enzymatic probing was performed to identify the
      secondary structures of the OFF conformations predicted by Mfold. Interestingly,
      enzymatic probing data of the riboswitch and its variants indicated that the
      riboswitch in its OFF state adopts two distinct structures. Moreover, further in
      vivo experiments suggested that both OFF structures contribute to the riboswitch
      function. A deeper understanding of how riboswitches function at the molecular
      level should enhance our ability to design synthetic riboswitches with new or
      improved characteristics.

PMID- 21902473
TI  - Sulfurization of dinucleoside phosphite triesters with chiral disulfides.
AB  - Sixteen chiral analogues of phenylacetyl disulfide (PADS) and 5-methyl-3H-1,2,4
      dithiazol-3-one (MEDITH) were used to sulfurize five dithymidine phosphite
      triesters, each incorporating a beta-cyanoethoxy or siloxy group. Each mixture of
      S(P):R(P) phosphite triester diastereomers was combined with approximately one
      fourth of an equivalent of each of the sulfurizing reagents, and the R(PS):S(PS)
      diastereomer ratios of the resulting phosphite sulfides or phosphorothioates were
      determined by reverse-phase HPLC. Diastereoselectivities and corresponding
      diastereomeric excess (de) values were calculated by correcting for the starting
      triester diastereomer ratios. The highest de values for R(PS) and S(PS)
      phosphorothioates were 14.7% and 7.9%, respectively, both using MEDITH analogues.

PMID- 21902474
TI  - The role of initiator tRNAimet in fidelity of initiation of protein synthesis.
AB  - The proper arrangement of amino acids in a protein determines its proper
      function, which is vital for the cellular metabolism. This indicates that the
      process of peptide bond formation requires high fidelity. One of the most
      important processes for this fidelity is kinetic proofreading. As biochemical
      experiments suggest that kinetic proofreading plays a major role in ensuring the
      fidelity of protein synthesis, it is not certain whether or not a misacylated
      tRNA would be corrected by kinetic proofreading during the peptide bond
      formation. Using 2-layered ONIOM (QM/MM) computational calculations, we studied
      the behavior of misacylated tRNAs and compared the results with these for cognate
      aminoacyl-tRNAs during the process of peptide bond formation to investigate the
      effect of nonnative amino acids on tRNAs. The difference between the behavior of
      initiator tRNA(i) (met) compared to the one for the elongator tRNAs indicates
      that only the initiator tRNA(i) (met) specifies the amino acid side chain.

PMID- 21902475
TI  - An azo-based PNA monomer: synthesis and spectroscopic study.
AB  - The full synthetic details and photospectroscopic characterization of a peptide
      nucleic acid (PNA) monomer suitable for Fmoc-based oligomerization chemistry that
      bears an azobenzene moiety as a base surrogate are reported. The monomer showed
      the ability to quench the fluorescence emission of fluorescein and pyrene
      luminophores and proved to be a competent Foster resonance energy transfer
      partner in a PNA-based molecular beacon.

PMID- 21902477
TI  - Prescribing authority during emergencies. Challenges for mental health care
      providers.

PMID- 21902478
TI  - To be or not to be my sister's keeper? A revised leagal framework safeguarding
      savior siblings' welfare.

PMID- 21902479
TI  - Middle of the road. Wakefield, Ohio, and pre-release planning for mentally-ill
      inmates.

PMID- 21902480
TI  - Informed consent for plastic surgery. Does it cut deeply enough?

PMID- 21902482
TI  - Social Learning Theory and Behavioral Therapy: Considering Human Behaviors within
      the Social and Cultural Context of Individuals and Families.
AB  - This article examines theoretical thoughts of social learning theory and
      behavioral therapy and their influences on human behavior within a social and
      cultural context. The article utilizes two case illustrations with applications
      for consumers. It points out the abundance of research studies concerning the
      effectiveness of social learning theory, and the paucity of research studies
      regarding effectiveness and evidence-based practices with diverse groups.
      Providing a social and cultural context in working with diverse groups with
      reference to social learning theory adds to the literature for more cultural
      considerations in adapting the theory to women, African Americans, and diverse
      groups.

PMID- 21902483
TI  - Adolescent preventive health and team-games-tournaments: five decades of evidence
      for an empirically based paradigm.
AB  - The problematic behaviors of teenagers and the subsequent negative consequences
      are extensive and well documented: unwanted pregnancy, substance abuse, violent
      behavior, depression, and social and psychological consequences of unemployment.
      In this article, the authors review an approach that uses a cooperative learning,
      empirically based intervention that employs peers as teachers. This intervention
      of choice is Teams-Games-Tournaments (TGT), a paradigm backed by five decades of
      empirical support. The application of TGT in preventive health programs
      incorporates elements in common with other prevention programs that are based on
      a public health orientation and constitute the essential components of health
      education, that is, skills training and practice in applying skills. The TGT
      intervention supports the idea that children and adolescents from various
      socioeconomic classes, between the ages of 8 and 18 and in classrooms or groups
      ranging in size from 4 to 17 members, can work together for one another. TGT has
      been applied successfully in such diverse areas as adolescent development,
      sexuality education, psychoactive substance abuse education, anger control,
      coping with depression and suicide, nutrition, comprehensive employment
      preparation, and family intervention. This article reviews the extensive research
      on TGT using examples of successful projects in substance abuse, violence, and
      nutrition. Issues are raised that relate to the implementation of preventive
      health strategies for adolescents, including cognitive aspects, social and family
      networks, and intervention components.

PMID- 21902484
TI  - General surgeon shortage in the United States: fact or fiction, causes and
      consequences.
AB  - There is evidence that supports a current undersupply of general surgeons with a
      potential for worsening workforce shortages in the future. This article examines
      this potential shortage along with its causes and possible consequences.

PMID- 21902485
TI  - Financial incentives to promote health care quality: the hospital acquired
      conditions nonpayment policy.
AB  - Over a decade ago it was estimated that in the United States 98,000 patients die
      each year from hospital acquired conditions (HAC). Recently it has been reported
      that this many patients now die annually from hospital acquired infections (HAI)
      alone. Currently, HAI affects 1.7 million U.S. citizens each year. Although these
      conditions are often called "preventable errors," some are associated with
      particular hospital and physician cultures, and many of these conditions, such as
      pressure ulcer formation and infections, may be a sign of low facility staffing
      levels. Protocols have been developed that have been shown to lower the incidence
      of many HAC, but these have been slow to be adopted. Voluntary reporting
      mechanisms to ensure health care quality are reported as having reduced
      effectiveness by the Joint Commission and U.S. Department of Health and Human
      Services, Office of Inspector General reports. Transparency and public education
      have also met with resistance, but in the case of infections now have the support
      of major national medical organizations. As a further initiative to promote
      quality, financial incentives have been implemented by the Centers for Medicare
      and Medicaid Services. Surgeons have lived under stringent financial incentives
      since the mid-1980s when they were placed under global surgical fees. Medicare
      currently must make expenditure reductions because it is at risk of becoming
      insolvent within the decade. Implementation of financial incentives should depend
      upon a balance between the nonpayment of providers for nonpreventable HAC verses
      the promotion of health care quality and patient safety, the reduction in patient
      morbidity and mortality, the spurring of mechanisms to further reduce HAC, and
      the recouping of taxpayer dollars for HAC that could have been prevented.

PMID- 21902486
TI  - An examination of the social, behavioral, and cognitive influences of infamous
      individuals on media consumers.
AB  - This article presents a substantial extant and predictive statement on social
      cognitive theory (SCT), a well-known interpersonal communication theory coined by
      Bandura (1986) and researched by prominent scholars in the social sciences. An
      important rationale behind conducting this analysis is that it provides several
      groundbreaking and unique applications of SCT through the exploration of infamous
      celebrities (i.e., Michael Jackson, Keith Richards, Robert Downey, Jr., and
      sexually perverted religious leaders) published in global media outlets. The
      objective is to demonstrate the socially influential effects that these notorious
      individuals pose on media consumers and interested parties, in line with
      theoretical assumptions posited by SCT.

PMID- 21902488
TI  - Response to Michael Ferguson's "Was Abraham Lincoln Gay?" (2010).

PMID- 21902489
TI  - Male street prostitution in Dublin: a psychological analysis.
AB  - This study assessed the mental health characteristics of 12 male street
      prostitutes (MSPs) in Dublin, with particular regard to issues of homelessness,
      substance abuse, depression, suicidal ideation, and self-esteem. Participants
      completed five psychometric tests, which indicated that all of the participants
      had above average levels of depression and suicidal ideation and low levels of
      self-esteem. This study found that candidates likely to become MSPs are young
      males with a combination of factors, including a background of childhood sexual
      or physical abuse, leaving school early, running away from home, and a dependence
      on heroin.

PMID- 21902490
TI  - Learning about a child's gay or lesbian sexual orientation: parental concerns
      about societal rejection, loss of loved ones, and child well being.
AB  - This article reports the results of a study examining heterosexual parents'
      concerns upon learning about their children's gay or lesbian sexual orientations.
      Three areas of parental concern are noted: (a) those about what society thinks of
      them because they have gay or lesbian children, (b) those about being rejected by
      loved ones, and (c) concerns for their child's physical and psychological well
      being. Results indicate that parents' concerns about having gay or lesbian
      children differ depending on the gender of the parent, gender of the child,
      awareness of stigma, and perceptions of parents' own gender role attributes.

PMID- 21902491
TI  - Creative work environments in sport organizations: the influence of sexual
      orientation diversity and commitment to diversity.
AB  - Drawing from creative capital theory, the purpose of this study was to examine
      the degree to which sexual orientation diversity and commitment to diversity were
      predictive of workplaces that fostered creativity. Data were collected from 653
      senior level athletic administrators and aggregated to the athletic department
      level of analysis (n = 199). Moderated regression indicated that sexual
      orientation diversity did not influence the presence of a creative work
      environment. There was however, a significant sexual orientation diversity *
      commitment to diversity interaction. When commitment to diversity was high, there
      was a positive association between sexual orientation diversity and a creative
      work environment; on the other hand, when commitment to diversity was low, the
      aforementioned relationship was negative. Results provide support for the notion
      that all diversity forms can be a source of enrichment and understanding, thereby
      benefiting the workplace.

PMID- 21902492
TI  - A paradise for LGBT rights? The paradox of Belgium.
AB  - How is it that a small country such as Belgium, with its reputation of relative
      conservatism, has jumped to the forefront of LGBT-friendly nations when it comes
      to the extension of rights to, and implementation of government policies for, its
      LGBT population? The analysis offered here focuses on a combination of six
      causes: the impact of wider secularization processes; the political history and
      culture of the country; the organization of especially the Flemish LGBT movement
      and reasons for its political effectiveness; mainstream social trends in national
      scapegoating hierarchies; the overall media environment; and the window of
      opportunity opened by the political landslide of 1999.

PMID- 21902493
TI  - Same-sex marriage and context-specific kinship terms.
AB  - This study investigates whether married gays and lesbians in Massachusetts are
      using the kinship terms commonly associated with marriage in referring to and
      introducing their marriage partners and, if not, whether alternative terms are
      being used in a variety of social contexts. We demonstrate through survey and
      interview data that marriage-related terms are used discriminately, are
      consciously chosen, and are context specific. Choices are dependent on a variety
      of factors related to personal demographics, speech community associations,
      intimacy, identity, and safety. A significant difference in the use of terms
      after legal marriage has occurred suggesting a shift in attitude.

PMID- 21902494
TI  - Individuals' beliefs about the etiology of same-sex sexual orientation.
AB  - We examined the relationships between beliefs about the etiology of having a same
      sex sexual orientation, sexual prejudice, and support for gay-relevant
      legislation using the justification-suppression model of prejudice as our
      theoretical foundation. Results indicated that more belief that a same-sex sexual
      orientation was due to nurture factors predicted less support for gay-relevant
      legislation, and that this relationship was mediated by levels of sexual
      prejudice. The opposite pattern was found for belief that a same-sex sexual
      orientation was due to nature factors. This suggests that beliefs about the
      etiology of sexual orientation may serve as justification (or suppression)
      factors in the expression of prejudice toward gay men and lesbians.

PMID- 21902495
TI  - Intergroup dialogue courses on sexual orientation: lesbian, gay and bisexual
      student experiences and outcomes.
AB  - Intergroup dialogue is a method of social justice education. Most intergroup
      dialogue research explores race and gender identities. Sexual orientation
      dialogues are uncommon and not yet examined empirically. This qualitative study
      explores sexual orientation dialogue courses from the perspective of lesbian,
      gay, and bisexual (LGB) student participants. Understanding target, or
      marginalized, group perspective of planned intergroup experiences is important
      given concerns raised in the literature. We document student motivations for
      participating in dialogues, core outcomes, and main challenges that arose in
      dialogue. Core outcomes include learning about and accepting one's sexual
      identity and empowerment. Challenges include those stemming from invisibility of
      sexual orientation identity. Recommendations are made for intergroup dialogue
      practice and research.

PMID- 21902499
TI  - Pharmacogenetic analyses of cisplatin-induced nephrotoxicity indicate a
      renoprotective effect of ERCC1 polymorphisms.
AB  - AIM: We investigated whether genetic polymorphisms may contribute to the
      interpatient variability of cisplatin-induced nephrotoxicity. PATIENTS & METHODS:
      Polymorphisms in the candidate genes GSTM1, GSTT1, OCT1, OCT2, LARP2, ERCC1,
      XRCC1 and EPO were analyzed for associations with nephrotoxicity in 79 cancer
      patients receiving cisplatin-containing chemotherapy. RESULTS: Higher cisplatin
      dose was associated with strongly decreased estimated glomerular filtration rates
      (eGFR) (r(2) = 0.205). Two highly genetically linked polymorphisms in the ERCC1
      gene, 8092C>A and Asn118Asn, were significantly associated with change in eGFR,
      accounting for an additional 13% of interindividual variability. Homozygous
      carriers of the 8092A allele in ERCC1 showed no reduction in eGFR, compared with
      the 11.5% mean eGFR decrease in C allele carriers (p = 0.004). Homozygous
      carriers of the C allele of Asn118Asn showed no reduction in eGFR, compared with
      the 12.8% mean eGFR decrease seen in T allele carriers (p = 0.047). Polymorphisms
      in the other candidate genes were not associated with cisplatin-induced
      nephrotoxicity. CONCLUSION: Genetic polymorphisms in ERCC1 may be valuable
      predictors of cisplatin-induced nephrotoxicity.

PMID- 21902500
TI  - Impact of genetic polymorphisms in ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genes on
      methadone therapy in Han Chinese patients.
AB  - AIM: The present study explored the integrative effect of genes encoding
      methadone pharmacokinetic and pharmacodynamic pathways on methadone maintenance
      doses in Han Chinese Patients. MATERIALS & METHODS: Genomic DNA was extracted
      from 321 opioid-dependent patients and 202 healthy controls, and realtime-PCR and
      PCR-RFLP were conducted to determine the genotypes. RESULTS: Pair-wise
      comparisons revealed that carriers of the variants ABCB1 3435C>T or CYP2B6 516G>T
      alleles were more likely to require a higher methadone dose than noncarriers
      (both p < 0.0001). On the other hand, carriers of the variant DRD2 -214A>G or
      939C>T allele had a twofold chance of requiring a lower methadone dose than
      noncarriers (p = 0.001). Proportional odds regression with adjustment of
      cofactors demonstrated that ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genetic variants
      were jointly correlated with optimal methadone dose (adjusted r(2) = 53%).
      CONCLUSIONS: These findings provide new insight to the fact that the
      interindividual variability of methadone dosage requirement is polygenetic and
      cannot be explained by a single-gene effect.

PMID- 21902501
TI  - Genetic polymorphisms in CYP3A4 are associated with withdrawal symptoms and
      adverse reactions in methadone maintenance patients.
AB  - AIM: Methadone maintenance therapy is one of the standard treatments for heroin
      addiction. The isozyme CYP3A4 of the CYP system is one of the metabolic enzymes,
      as well as CYP2B6, responsible for the metabolism of methadone. The aim of the
      present study is to evaluate the potential use of genetic polymorphisms in CYP3A4
      as biomarkers for the prediction of methadone treatment responses. MATERIALS &
      METHODS: A total of 366 Han Chinese methadone maintenance treatment patients in
      Taiwan were recruited in this study. Main clinical assessments included the
      clinical opioid withdrawal scale (COWS), the treatment emergent symptom scale
      (TESS) and the plasma concentrations of methadone and its metabolites. Genetic
      associations of six SNPs in the CYP3A4 gene were calculated using a general
      linear model. RESULTS: Genotypes and allele types of rs4646440 and rs2242480 were
      found to be significantly associated with the severity of withdrawal symptoms
      rated by COWS (p = 0.012, 0.0096, 0.017 and 0.012, respectively) as well as the
      side effects rated by TESS (p = 0.0089, 0.028, 0.0027 and 0.0085, respectively).
      The allele types associated with more severe withdrawal symptoms are also
      associated with more severe side effects and less betel nut (Areca catechu) use
      (p = 0.009 for rs4646440, p = 0.0063 for rs2242480). Further analyses on specific
      withdrawal symptoms in COWS showed that the genetic variants in rs4646440 are
      significantly associated with heart rate (allele type p = 0.0019). CONCLUSION:
      These results suggested that genetic variants in the CYP3A4 gene may be useful
      indicators for the severity of side effects and withdrawal symptoms for methadone
      treatment.

PMID- 21902502
TI  - Effect of a new functional CYP3A4 polymorphism on calcineurin inhibitors' dose
      requirements and trough blood levels in stable renal transplant patients.
AB  - AIMS: CYP3A4 is involved in the oxidative metabolism of many drugs and
      xenobiotics including the immunosuppressants tacrolimus (Tac) and cyclosporine
      (CsA). The objective of the study was to assess the potential influence of a new
      functional SNP in CYP3A4 on the pharmacokinetic parameters assessed by dose
      requirements and trough blood levels of both calcineurin inhibitors (CNI) in
      stable renal transplant patients. PATIENTS & METHODS: A total of 99 stable renal
      transplant patients receiving either Tac (n = 49) or CsA (n = 50) were genotyped
      for the CYP3A4 intron 6 C>T (rs35599367) and CYP3A5*3 SNPs. Trough blood levels
      ([Tac](0) or [CsA](0) in ng/ml), dose-adjusted [Tac](0) or [CsA](0) (ng/ml per
      mg/kg bodyweight) as well as doses (mg/kg bodyweight) required to achieve target
      concentrations were compared among patients according to allelic status for
      CYP3A4 and CYP3A5. RESULTS: Dose-adjusted concentrations were 2.0- and 1.6-fold
      higher in T-variant allele carriers for the CYP3A4 intron 6 C>T SNP compared with
      homozygous CC for Tac and CsA, respectively. When CYP3A4/CYP3A5 genotypes were
      combined, the difference was even more striking as the so-defined CYP3A poor
      metabolizer group presented dose-adjusted concentration 1.6- and 4.1-fold higher
      for Tac, and 1.5- and 2.2-fold higher for CsA than the intermediate metabolizer
      and extensive metabolizer groups, respectively. Multiple linear regression
      analysis revealed that, taken together, both CYP3A4 intron 6 and CYP3A5*3 SNPs
      explained more than 60 and 20% of the variability observed in dose-adjusted
      [Tac](0) and [CsA](0), respectively. CONCLUSION: The CYP3A4 intron 6 C>T
      polymorphism is associated with altered Tac and CsA metabolism. CYP3A4 intron 6
      C>T along with CYP3A5*3 (especially for Tac) pharmacogenetic testing performed
      just before transplantation may help identifying patients at risk of CNI
      overexposure and contribute to limit CNI-related nephrotoxicity by refining the
      starting dose according to their genotype. Original submitted 5 May 2011;
      Revision submitted 29 June 2011.

PMID- 21902503
TI  - ABCB1 polymorphisms and neuropsychiatric adverse events in oseltamivir-treated
      children during influenza H1N1/09 pandemia.
AB  - AIMS: To examine the safety profile of oseltamivir in children and evaluate the
      impact of P-glycoprotein polymorphisms on the incidence of neuropsychiatric
      adverse events (NPAE) in oseltamivir-treated children. SUBJECTS & METHODS: This
      prospective cohort study was conducted in our tertiary care pediatric hospital
      (University Hospitals of Geneva, Switzerland) during the H1N1 pandemia, between 1
      October 2009 and 31 January 2010. All newborn to 18 year-old patients presenting
      at the emergency department with a flu-like illness were eligible for inclusion.
      Adverse events were systematically recorded by pediatricians and/or by parents at
      home using a diary card, with a 30-day follow-up period. The causality assessment
      of oseltamivir in NPAE was performed by two clinical pharmacologists. After
      informed consent, enrolled patients were also genotyped for ABCB1 3435C>T
      (rs1045642) and 2677G>T/A (rs2032582) polymorphisms. RESULTS: Among the 42 H1N1
      infected, oseltamivir-treated children who were genotyped for ABCB1 3435C>T and
      2677G>T/A variants, 36% presented NPAE. When examining the association between
      the diplotype and the development of NPAE, we observed that the frequency of NPAE
      displayed a 'genotype-trend effect' with the variant and the wild-type subgroups
      at the two far ends. A total of 11% of the 2677GG-3435CC individuals (wild-type
      homozygous) presented NPAE, compared with 39% of the individuals being
      heterozygous for at least one variant allele and 67% of the 2677TT-3435TT
      individuals (homozygous variants) (p = 0.149, nonsignificant). CONCLUSION: These
      observations suggest a potential influence of ABCB1 polymorphisms in oseltamivir
      related NPAE, maybe as a result of an enhanced permeability of the blood-brain
      barrier to oseltamivir

PMID- 21902505
TI  - FRONTLINE: secure attachment and traumatic life events.

PMID- 21902506
TI  - The psychoanalysis and death of George Gershwin: an American tragedy.
AB  - The story of the noted composer George Gershwin's psychoanalysis and death
      resulting from an undiagnosed brain tumor 70 years ago are known today only in a
      garbled, incomplete form through biography and legend rather than history among
      psychoanalysts, neurologists, and neurosurgeons. This article examines his
      psychoanalysis with Gregory Zilboorg and the events and course of his final
      illness to the extent possible with the historical material now available. It
      provides an account of the behavior of his psychoanalyst in a variety of contexts
      as well as the actions of the other physicians attending him. We cannot know, but
      can only infer, what went on in his psychoanalytic sessions or his medical
      examinations; about this the reader will have to draw his or her own conclusions.

PMID- 21902508
TI  - On emergence: a neo-psychoanalytic essay on change and science.
AB  - The neo-psychoanalytic paradigm re-establishes the connection between
      psychodynamics and evolution. This allows us to transcend the limitations of
      dualistic metapsychology, and to make seminal contributions to traditional
      science. The new paradigm employs the concept of emergence, the potential for
      change in the evolutionary and clinical process. Emergence is described as
      originating with the Big Bang, but also is reflected at much higher levels, for
      example, biochemistry, or the capacity of the evolved mind to produce insights in
      psychotherapy. The constraints of dualistic theories are examined. A neuron-based
      view of change illustrates the evolution of traditional science as well as the
      neuron, itself. The new mind paradigm recognizes individual, familial,
      communitarian, and global reciprocal influences mediated by culture and
      illustrated by the extended mind and the democratic spirit. Thus both traditional
      and psychodynamic sciences are undergoing revolutionary changes in their common
      efforts to better understand the mechanisms of knowledge, relationship and
      consciousness. The boundaries of the self and the consultation suite are also
      expanded in this view. Following a survey of invagination, the work is concluded
      by an application of emergence theory to the creationist controversy and Freud's
      views of religion.

PMID- 21902507
TI  - The impact of cultural evolution on the ego ideal, depression, psychosis, and
      suicide: a South India community study of the widow.
AB  - Cultural factors have a significant impact on the manifestation of psychiatric
      illness and the development of the ego ideal. The evolution of the widow's
      cultural role in a South India village provides insight on the ego ideal through
      several generations. As treatment of widows changed so that their appearance
      became indistinguishable from other women, they no longer became objects of
      revulsion. A case study approach documents the interrelationship of changes in
      the cultural ego ideal on psychiatric illness among widows in a South India
      village over a period of more than four decades.

PMID- 21902509
TI  - The partnership of psychoanalysis and psychiatry in the treatment of psychosis
      and borderline states: its evolution in North America.
AB  - The history of psychiatry is about two hundred years old and that of
      psychoanalysis more than a hundred, with an important anniversary of the latter
      in 2011. Freud renewed and humanized psychiatry by enriching its static
      descriptive method with the new dynamic and interpretive discoveries of
      psychoanalysis. Freud's innovations, while developed in Europe, were integrated
      into psychiatry briefly by the Swiss School but mainly in the United States.
      After many years of fruitful collaboration psychiatry and psychoanalysis seemed
      to part company in the U.S. in the last few decades. However, the tradition of
      combining psychiatric care with dynamic principles is still considered valid in
      the treatment of psychoses and severe personality disorders.

PMID- 21902510
TI  - The study of psychic trauma.
AB  - This article starts from the DSM definition of psychic trauma. A central source
      in this field is the 1992 book by Judith Herman. One line of investigation is the
      sexual abuse of women and children. In an early phase, both Janet and Freud
      described dissociation as a reaction to trauma. In 1897, Freud disputed the
      reality of sexual trauma, a position countered later by Ferenczi. In a later
      phase, this subject was investigated by the American feminist movement. Studies
      of physical abuse are then described, followed by mental abuse and neglect.
      Another line of investigation is combat neurosis. The two lines converged in the
      definition of PTSD and its incorporation into the DSM in 1980. The views on
      trauma of John Bowlby and Alice Miller are also discussed. The integration of the
      relational model in psychoanalysis with the trauma literature is presented. The
      most recent advances are located in neurobiology. The discussion makes a
      preliminary investigation of the remote causes of war and sexual violence.

PMID- 21902511
TI  - The role of identification in dynamic psychiatry and psychotherapy.
AB  - Identification-a psychic process in which a person takes on characteristics of
      another-is a concept important to the understanding of human nature. It plays an
      important role in how our personalities develop, in our ability to deal with
      life's stresses, and in how we interact with other people. Knowledge of its
      manifestations is essential to dynamic psychiatry and to its applications in
      psychotherapy. This article defines identification and reviews its role in
      development and as a defense. It discusses its role in the psychopathology of
      disorders commonly encountered in psychotherapy practice-depression and anxiety
      states reactive to losses in life, and borderline states. Clinical vignettes
      illustrate how identification functions in these conditions, and also how
      identifications reveal themselves in the transference and are utilized in
      psychotherapy. A teaching vignette illustrates how important it is that residents
      learning the art of psychotherapy appreciate the therapeutic potential of
      identification. The article maintains that, although it often goes unrecognized,
      identification with the therapist is one of the most effective therapeutic
      devices in the transference.

PMID- 21902512
TI  - Aspects of psychodynamic neuropsychiatry III: magic spells, the placebo effect,
      and neurobiology.
AB  - Through a case study, the importance of supporting the positive transference is
      stressed-from both a psychological and neurobiological perspective. The article
      argues that the neurobiology of expectation underlies transference. This
      neurobiology has been investigated particularly over the past several decades in
      work concerning the placebo effect. By understanding the neurobiology of
      expectation, one gains a better understanding of the neurobiology of the
      transference. This enables clinical predictions-and decisions-that are informed
      not just by the teachings of psychology but also by the science of biology.

PMID- 21902515
TI  - News from Clinical Research Office of the Endourological Society (CROES).

PMID- 21902516
TI  - Welcome to the World Congress of Endourology Highlights edition.

PMID- 21902517
TI  - Urologic robot-assisted laparoendoscopic single-site surgery using a homemade
      single-port device: a single-center experience of 68 cases.
AB  - PURPOSE: To describe our experience with robot-assisted laparoendoscopic single
      site (R-LESS) surgeries and evaluate a homemade port system as an effective
      access technique. PATIENTS AND METHODS: Between May 2009 and April 2010, 68
      consecutive R- LESS urologic operations were performed in our institution. A 4 to
      5 cm long incision was made over the umbilicus. After the inner ring of the
      Alexis wound retractor was placed into the peritoneum, a common size 7 surgical
      glove was then applied over the external side of the wound retractor. A homemade
      single port was established by inserting two 12-mm trocars and two 8-mm trocars
      through fingers of a surgical glove and securing it to the port. RESULTS: Sixty
      eight patients underwent R-LESS, including partial nephrectomy in 51,
      nephroureterectomy in 12, radical nephrectomy and adrenalectomy in 2 each, and
      simple nephrectomy in 1. Mean patient age was 56 years (range 16-81 y). Mean body
      mass index was 23.9 kg/m(2) (range 17.2-32.9 kg/m(2)). The mean operative time
      was 219 minutes (range 109-382 min). Mean estimated blood loss 319 mL (range 50
      1550 mL), and change in hematocrit was 5.2 % (range 0.0-14.8%). At a mean follow
      up of 8 months, there were no port-related complications, and cosmesis was
      excellent. CONCLUSIONS: R-LESS is feasible and can be safely applied to a variety
      of urologic operations, considering the low intraoperative complication rate. Our
      homemade single-port device provides adequate range of motion and is more
      flexible in port placement for R-LESS than the current multichannel port.

PMID- 21902518
TI  - Selective renal parenchymal clamping in robot-assisted laparoscopic partial
      nephrectomy: a multi-institutional experience.
AB  - PURPOSE: We describe our multi-institutional experience using a laparoscopic
      clamp to induce selective regional ischemia during robot-assisted laparoscopic
      partial nephrectomy (RALPN) without hilar occlusion. PATIENTS AND METHODS: A
      retrospective review of Institutional Revew Board-approved databases of patients
      who underwent selective regional clamping during RALPN at four institutions was
      performed. RESULTS: In 20 patients who were treated for elective indications,
      RALPN with parenchymal clamping was successful in 17 (85%). Mean age was 63 years
      (24-78 y). Median tumor diameter was 2.2 cm (1.1-7.2 cm). Mass location was polar
      in 13 (76%) and interpolar in 4 (24%). Median R.E.N.A.L. nephrometry score was 6
      (4-10). Median overall operative time was 190 minutes (129-309 min), while
      selective clamp time was 26 minutes (19-52 min). Collecting system repair
      occurred in 8 (47%) patients. No patients needed a blood transfusion. There was
      no significant difference in preoperative (median 86 mL/min/1.73 m(2)) and
      immediate postoperative glomerular filtration rate (GFR) (median 78 mL/min/1.73
      m(2), P=0.33) or with the most recent GFR (median 78 mL/min/1.73 m(2), P=0.54) at
      a mean follow-up of 6.1 months (1.2-11.9 mos). Final pathology determination
      revealed renal-cell carcinoma in 71% with no positive margins on frozen or final
      evaluation. In three additional patients who were undergoing RALPN, bleeding
      because of incomplete distal clamp compression necessitated subsequent central
      hilar clamping for the completion of the procedure. CONCLUSIONS: In our
      preliminary multi-institutional experience, regional ischemia using a
      laparoscopic parenchymal clamp is feasible during RALPN for hemostasis. Careful
      preoperative selection of patients is needed to determine ideal patient and tumor
      characteristics. Further comparison studies are necessary to determine the true
      utility of this technique.

PMID- 21902519
TI  - An objective scoring system for laparoscopic nephrectomy.
AB  - BACKGROUND AND PURPOSE: The current first-line recommended modality for
      nephrectomy is by the laparoscopic approach. This is one of the most frequent
      laparoscopic interventions conducted in urology. From a skills acquisition and
      delivery perspective in minimally invasive urologic surgery, there is a paucity
      of objective scoring systems for advanced laparoscopic urologic procedures. We
      developed a system of direct observation with structured criteria to evaluate the
      surgical conduction of laparoscopic nephrectomy (LN). We tested the application
      and preliminary validity of the scoring system. METHODS: Sixty cases of
      prerecorded LN performed in four teaching hospitals were each analyzed by four
      mentors. Each mentor scored each case based on a 100-point scoring systemthat
      comprised 20 key steps for LN (each step ranging 0 to 5). Steps included port
      placement and safety checks in addition to the actual case. In addition, a
      negative marking system based on a 50-point index scoring system was deployed
      such that technically unsound techniques were penalized. The sum of the two
      resulted in the final score. The final scores independently submitted for each
      recorded case were analyzed and compared. The system was then used to predict the
      experience of a surgeon for 10 pilot cases. The cases included a mix of five
      fellows and five experienced laparoscopic urologic surgeons. The cases were
      blinded to the independent assessors. A further 20 cases involving 10 cases
      performed by a trainee who sufficiently completed training (as deemed by the
      recent award of a certificate of specialist training in urology) vs one who is
      not ready were reviewed. RESULTS: There was no significant difference in the
      scores submitted by each of the four mentors for each of the cases observed.
      There was a strong correlation between overall score and seniority/experience of
      the performing surgeon of each case; ie, it was able to predict whether an
      experienced surgeon or laparoscopic fellow performed the case. It was able to
      predict accurately between a trainee who sufficiently completed training vs one
      who is "not ready." CONCLUSION: The scoring system was a reliable tool for
      assessing the performance of LN and accurately predicts the level of experience
      of the surgeon. This system could be a useful supplementary tool for assessing
      the baseline skill and progress of trainees.

PMID- 21902524
TI  - Genome diagnostics: next-generation sequencing, new genome-wide association
      studies and clinical challenges.

PMID- 21902525
TI  - Oncologic theranostics: recognition of this concept in antigen-directed cancer
      therapy for colorectal cancer with anti-TAG-72 monoclonal antibodies.

PMID- 21902526
TI  - Progress and challenges in developing a molecular diagnostic test for
      neurofibromatosis type 1.

PMID- 21902528
TI  - APTIMA(r) Trichomonas vaginalis, a transcription-mediated amplification assay for
      detection of Trichomonas vaginalis in urogenital specimens.
AB  - The APTIMA((r)) Trichomonas vaginalis (APTIMA TV; Gen-Probe Inc.) assay is the
      only amplification-based assay for T. vaginalis (TV) currently cleared by the US
      FDA. The assay was cleared in April 2011. APTIMA TV utilizes target capture
      specimen processing, transcription-mediated amplification and chemiluminescent
      probe hybridization for the qualitative detection of TV ribosomal RNA. The assay
      is used for the screening/diagnosis of trichomoniasis in women. Specimen types
      that can be used include physician-collected endocervical swabs, vaginal swabs,
      endocervical specimens collected in PreservCyt((r)) (Thin Prep, Hologic
      Incorporated, MA, USA) solution and female urine specimens. The APTIMA TV assay
      has shown superior performance in side-by-side comparisons with other diagnostic
      methods in all patient populations and specimen types tested. Clinical
      sensitivity and specificity are >95 and 98%, respectively. The APTIMA TV assay
      fills a significant void in sexually transmitted infection diagnostics.

PMID- 21902529
TI  - Biomarkers research in Europe: focus on personalized medicine.
AB  - The sixth annual European Biomarkers Summit took place in London, UK, on 18-19
      May 2011. It was part of a larger event, organized by Select Biosciences, with
      meetings on molecular diagnostics, single cell analysis and theranostics for
      personalized medicine. The Biomarkers Summit featured 17 invited talks from
      academics and industry researchers, a number of poster presentations and
      exhibitions from several companies marketing biomarker-related technologies and
      consumables. The focus was broad, covering various aspects of biomarker
      discovery, qualification, and applications, and a variety of diseases including
      cancer, neurodegenerative conditions and infectious diseases. Gene-based, as well
      as protein-based, platforms for biomarkers identification and analysis were
      discussed.

PMID- 21902530
TI  - Epigenetic alteration of microRNAs in feces of colorectal cancer and its clinical
      significance.
AB  - MicroRNAs regulate target gene expression through translation repression or mRNA
      decay, and they are emerging as important modulators in cellular pathways.
      Previous studies have shown the occurrence of epigenetically modified miRNAs in
      colorectal cancer (CRC), identifying these miRNA methylation signatures may
      provide candidate markers for the detection of malignant colonocytes. Fecal-based
      tests are widely adopted as noninvasive methods for CRC diagnosis, thus several
      studies have attempted to use miRNAs from feces as CRC markers. This article
      evaluates a recently published study investigating the usefulness of
      epigenetically silenced miRNAs in fecal specimens, including miR-34b/c and miR
      148a, as potential markers for CRC screening and prognosis.

PMID- 21902531
TI  - Critical role of laser microdissection for genetic, epigenetic and proteomic
      analyses in pancreatic cancer.
AB  - Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease, and molecular
      studies to unravel novel biomarkers and therapeutic targets are warranted.
      However, PDAC is characterized by different precursor lesions, as well as by an
      intense desmoplastic reaction, with islet of neoplastic cells often representing
      a minor population. Moreover, normal ductal cells, which are considered to be the
      normal counterpart of pancreatic adenocarcinoma cells, comprise approximately 5%
      of the total population of cells making up this organ. For all these reasons,
      molecular techniques to identify critical mutations, as well as the pattern of
      altered mRNA/microRNA/protein expression should be performed on selected
      pancreatic cell subpopulations. Therefore, the use of the newest laser
      microdissection techniques is critical for the analysis of PDAC biological
      characteristics. This article highlights the most recent and clinically relevant
      aspects of genetic, epigenetic and proteomic analyses of PDAC from the
      perspective of the application of laser microdissection.

PMID- 21902532
TI  - Expanding DNA diagnostic panel testing: is more better?
AB  - During the last 25 years, a small number of meaningful DNA-based diagnostic tests
      have been available to aid in the diagnosis and subsequent treatment of heritable
      disorders. These tests have targeted a limited number of genes and are often
      ordered in serial testing strategies in which results from one preliminary test
      dictate the subsequent test orders. This approach can be both time and resource
      intensive when a patient requires several genes to be sequenced. Recently, there
      has been much discussion regarding how 'massively parallel' or 'next-generation'
      DNA sequencing will impact clinical care. While the technology promises to reduce
      the cost of sequencing an entire human genome to less than US$1000, one must
      question the diagnostic utility of complete genome sequencing for routine
      clinical testing, given the many interpretive challenges posed by this approach.
      At present, it appears next-generation DNA sequencing may provide the greatest
      benefit to routine clinical testing by enabling comprehensive multigene panel
      sequencing. This should provide an advantage over traditional Sanger-based
      sequencing strategies while limiting the total test output to sets to genes with
      known diagnostic value. This article will discuss the current and near future
      state of clinical testing approaches and explore what challenges must be
      addressed in order to extract diagnostic value from whole-exome sequencing and
      whole-genome sequencing, using hereditary colon cancer as an example.

PMID- 21902533
TI  - Microfluidic platforms for performing surface-based clinical assays.
AB  - The need for fast, specific and portable diagnostic systems for clinical assays
      has, in recent years, led to an explosion of research into microfluidic chip
      based immunoassays towards rapid point-of-care analysis. Such devices exploit
      small dimensions, superior fluidic control and low reagent volumes to allow a
      number of clinically important procedures to be achieved with improvements on
      conventional methods, many of which rely on the surface-based binding of antigens
      to antibodies. Here, we discuss recent developments and innovations in the area
      of on-chip surface-based immunoassays and provide an outlook on the potential of
      such platforms for future diagnostics.

PMID- 21902534
TI  - Translating potential biomarker candidates for schizophrenia and depression to
      animal models of psychiatric disorders.
AB  - Schizophrenia and major depressive disorder are severe mental illnesses, which
      are diagnosed based on patient interviews. Despite many years of extensive
      research, scientists have not yet fully deciphered how genetic and environmental
      factors interact to cause these illnesses. Biomarker tests that can confirm
      diagnoses of schizophrenia or depression are only now beginning to emerge, and
      could result in a paradigm shift in this field. These tests will help to evaluate
      the validity of animal models of psychiatric disorders, which are currently
      characterized based on behavioral measures. In this article, we explore the
      utility of translating both behavioral and molecular phenotypes of such models to
      the corresponding human disorders. This approach may help to provide construct
      validity to animal models and could lead to the identification of models
      corresponding to defined subtypes of neuropsychiatric disorders based on
      molecular profiles. Here, we review the molecular and biological pathway
      alterations that have been found in animal models of schizophrenia and depression
      and focus on those that are mirrored by similar abnormalities in human patients.
      Such parallels may provide insight into the validity of specific animal models
      and therefore help to provide more valuable and accurate tools for the discovery
      and development of improved psychiatric medications.

PMID- 21902535
TI  - Single-cell gene-expression profiling and its potential diagnostic applications.
AB  - Gene-expression profiling has been successfully applied in various diagnostic
      applications, but its full capacity is yet to be realized. Samples are generally
      prepared from a mixture of different cells that are present in unknown
      proportions. Cells are, in many aspects, unique in their characteristics and this
      heterogeneity confounds the expression profile. The development of new and robust
      techniques to measure gene expression in single cells opens new avenues in
      molecular medicine. Today, gene-expression profiles of individual cells can be
      measured with high precision and accuracy, identifying different cell types as
      well as revealing heterogeneity among cells of the same kind. Here, we review
      practical aspects of single-cell gene-expression profiling using reverse
      transcription quantitative real-time PCR and its potential use in diagnostics.

PMID- 21902536
TI  - Molecular diagnostics: harmonization through reference materials, documentary
      standards and proficiency testing.
AB  - There is a great need for harmonization in nucleic acid testing for infectious
      disease and clinical genetics. The proliferation of assay methods, the number of
      targets for molecular diagnostics and the absence of standard reference materials
      contribute to variability in test results among laboratories. This article
      provides a comprehensive overview of reference materials, related documentary
      standards and proficiency testing programs. The article explores the
      relationships among these resources and provides necessary information for people
      practicing in this area that is not taught in formal courses and frequently is
      obtained on an ad hoc basis. The aim of this article is to provide helpful tools
      for molecular diagnostic laboratories.

PMID- 21902538
TI  - Gene therapy for traumatic central nervous system injury and stroke using an
      engineered zinc finger protein that upregulates VEGF-A.
AB  - Recent studies have identified anti-apoptotic functions for vascular endothelial
      growth factor (VEGF) in the central nervous system (CNS). However, VEGF therapy
      has been hampered by a tendency to promote vascular permeability, edema, and
      inflammation. Recently, engineered zinc finger proteins (ZFPs) that upregulate
      multiple forms of VEGF in their natural biological ratios, have been developed to
      overcome these negative side effects. We used retinal trauma and ischemia models,
      and a cortical pial strip ischemia model to determine if VEGF upregulating ZFPs
      are neuroprotective in the adult CNS. Optic nerve transection and ophthalmic
      artery ligation lead to the apoptotic degeneration of retinal ganglion cells
      (RGCs) and are, respectively, two highly reproducible models for CNS trauma or
      ischemia. Adeno-associated vectors (AAV) vectors encoding VEGF-ZFPs (AAV-VEGF
      ZFP) significantly increased RGC survival by ~twofold at 14 days after optic
      nerve transection or ophthalmic artery ligation. Furthermore, AAV-VEGF-ZFP
      enhanced recovery of the pupillary light reflex. RECA-1 immunostaining
      demonstrated no appreciable differences between retinas treated with AAV-VEGF-ZFP
      and controls, suggesting that AAV-VEGF-ZFP treatment did not affect retinal
      vasculature. Following pial strip of the forelimb motor cortex, brains treated
      with an adenovirus encoding VEGF ZFPs (AdV-ZFP) showed higher neuronal survival,
      accelerated wound contraction, and reduced lesion volume between 1 and 6 weeks
      after injury. Behavioral testing using the cylinder test for vertical exploration
      showed that AdV-VEGF-ZFP treatment enhanced contralateral forelimb function
      within the first 2 weeks after injury. Our results indicate that VEGF ZFP therapy
      is neuroprotective following traumatic injury or stroke in the adult mammalian
      CNS.

PMID- 21902539
TI  - Ethanol intoxication is associated with a lower incidence of admission
      coagulopathy in severe traumatic brain injury patients.
AB  - The aim of this study was to determine the impact of ethanol (ETOH) on the
      incidence of severe traumatic brain injury (sTBI)-associated coagulopathy and to
      examine the effect of ETOH on in-hospital outcomes in patients sustaining sTBI.
      Patients admitted to the surgical intensive care unit from June 2005 through
      December 2008 following sTBI, defined as a head Abbreviated Injury Scale (AIS)
      score >=3, were retrospectively identified. Patients with a chest, abdomen, or
      extremity AIS score >3 were excluded to minimize the impact of extracranial
      injuries. Criteria for sTBI-associated coagulopathy included thrombocytopenia
      and/or elevated International Normalized Ratio (INR) and/or prolonged activated
      partial thromboplastin time (aPTT). The incidence of admission coagulopathy, in
      hospital complications, and mortality were compared between patients who were
      ETOH positive [ETOH (+)] and ETOH negative [ETOH (-)]. During the study period,
      there were 439 patients with ETOH levels available for analysis. Overall, 46.5%
      (n=204) of these patients were ETOH (+), while 53.5% (n=235) were ETOH (-).
      Coagulopathy was significantly less frequent in the ETOH (+) patients compared to
      their ETOH (-) counterparts (5.4% versus 15.3%; adjusted p<0.001). In the forward
      logistic regression analysis, a positive ETOH level proved to be an independent
      protective factor for admission coagulopathy [OR (95% CI)=0.24 (0.10,0.54;
      p=0.001]. ETOH (+) patients had a significantly lower in-hospital mortality rate
      than ETOH (-) patients [9.8% versus 16.6%; adjusted p=0.011; adjusted OR (95%
      CI)=0.39 (0.19,0.81)]. For brain-injured patients arriving alive to the hospital,
      ETOH intoxication is associated with a significantly lower incidence of early
      coagulopathy and in-hospital mortality. Further research to establish the
      pathophysiologic mechanisms underlying any potential beneficial effect of ETOH on
      the coagulation system following sTBI is warranted.

PMID- 21902540
TI  - Laparoscopic partial nephrectomy versus laparoscopic ablative therapy: a
      comparison of surgical and functional outcomes in a matched control study.
AB  - BACKGROUND AND PURPOSE: Patients who are undergoing laparoscopic ablative therapy
      (LAT) are often older with more comorbidities in comparison with patients who are
      undergoing laparoscopic partial nephrectomy (LPN). A matched control study was
      performed to compare the surgical and functional outcomes of LPN and LAT.
      PATIENTS AND METHODS: A prospectively maintained database of 250 patients who
      underwent nephron-sparing surgery was explored. Fifty-one LAT patients (21 and 30
      laparoscopic radiofrequency and cryoablation, respectively) were matched with 51
      LPN patients. A comparison of preoperative, operative, and postoperative outcomes
      was performed. RESULTS: The groups were similar in age, sex, body mass index,
      preoperative estimated glomerular filtration rate (eGFR), number of comorbidities
      and tumor size. Patients who were undergoing LAT had a lower incidence of
      endophytic tumor and higher incidence of upper pole and midpolar tumors. Hilar
      vessels clamping was performed in LPN (47/51 patients). Mean estimated blood loss
      and operative time were higher in those undergoing LPN (P<0.01). There was no
      significant difference in transfusion rate and hospital stay, however. Mean
      follow-up was 27 and 18 months in LAT and LPN, respectively (P<0.01). The mean
      percent decline of eGFR at the last follow-up was 10 (95% confidence interval
      [CI]: 4-15) and 7.5 (95% CI: 4-11), respectively (P<0.43). In comparison with
      baseline, eGFR declined significantly (P<0. 01), but there was no difference
      between the groups. CONCLUSION: Despite renal ischemia, longer operative time,
      and higher blood loss associated with LPN, the hospital stay and long-term
      functional outcomes are similar to those of LAT in a matched control study.

PMID- 21902541
TI  - Re: reduced radiation exposure with the use of an air retrograde pyelogram during
      fluoroscopic access for percutaneous nephrolithotomy (from: Lipkin ME, Mancini
      JG, Zilberman DE, et al. J Endourol 2011;25:563-567).

PMID- 21902543
TI  - Red blood cell engineering in stroma and serum/plasma-free conditions and long
      term storage.
AB  - In vitro generation of artificial red blood cells (RBCs) is very important to
      overcome insufficient and unsafe blood supply. Despite recent progresses in RBCs
      engineering from several stem cell sources, none of them could succeed in
      generation of functional RBCs in the absence of serum/plasma and feeder cells.
      Without the elimination of serum and plasma, human RBC engineering in a large
      scale is impossible, especially for the future bioreactor system. Using an
      appropriate combination of cost-effective and safe reagents, the present study
      demonstrated the terminal maturation of hematopoietic stem cells into enucleated
      RBCs, which were functional comparable to donated human RBCs. Surprisingly, the
      viability of erythroid cells was higher in our serum- and feeder-free culture
      condition than in the previous serum-added condition. This was possible by
      supplementation with vitamin C in media and hypothermic conditions. Also, our
      report firstly presents the storability of artificial RBCs, which possibility is
      essential for clinical application. In summary, our report demonstrates
      engineering of human applicable RBCs with a dramatically enhanced viability and
      shelf-life in both serum- and stroma-free conditions. This innovative culture
      technology could contribute to the realization of the large-scale pharming of
      human RBCs using bioreactor systems.

PMID- 21902542
TI  - Adjuvant hormonal therapy use among women with ductal carcinoma in situ.
AB  - OBJECTIVE: In the absence of consistent guidelines for the use of adjuvant
      hormonal therapy (HT) in treating ductal carcinoma in situ (DCIS), our purpose
      was to explore a variety of factors associated with discussion, use, and
      discontinuation of this therapy for DCIS, including patient, tumor, and treatment
      related characteristics and physician-patient communication factors. METHODS: We
      identified women from eight California Cancer Registry regions diagnosed with
      DCIS from 2002 through 2005, aged >=18 years, of Latina or non-Latina white
      race/ethnicity. A total of 744 women were interviewed an average of 24 months
      postdiagnosis about whether they had (1) discussed with a physician, (2) used,
      and (3) discontinued adjuvant HT. RESULTS: Although 83% of women discussed
      adjuvant HT with a physician, 47% used adjuvant HT, and 23% of users reported
      discontinuation by a median of 11 months. In multivariable adjusted analyses,
      Latina Spanish speakers were less likely than white women to discuss therapy
      (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.18-0.69) and more likely to
      discontinue therapy (OR 2.67, 95% CI 1.05-6.81). Seeing an oncologist for follow
      up care was associated with discussion (OR 5.10, 95% CI 3.14-8.28) and use of
      therapy (OR 4.20, 95% CI 2.05-8.61). Similarly, physician recommendation that
      treatment was necessary vs. optional was positively associated with use (OR 11.2,
      95% CI 6.50-19.4) and inversely associated with discontinuation (OR 0.38, 95% CI
      0.19-0.73). CONCLUSIONS: Physician recommendation is an important factor
      associated with use and discontinuation of adjuvant HT for DCIS. Differences in
      discussion and discontinuation of therapy according to patient characteristics,
      particularly ethnicity/language, suggest challenges to physician-patient
      communication about adjuvant HT across a language barrier.

PMID- 21902544
TI  - RNA interference-mediated vascular endothelial growth factor-C reduction
      suppresses malignant progression and enhances mitomycin C sensitivity of bladder
      cancer T24 cells.
AB  - Vascular endothelial growth factor-C (VEGF-C) has been found to be significantly
      associated with lymphangiogenesis and regional lymph node metastasis in various
      human tumors. The present work was aimed to explore the role of VEGF-C in
      malignant progression of human bladder cancer T24 cell line. First, the
      expression of VEGF-C in T24 cells was detected by western blotting. The 3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was employed to
      measure the cellular proliferation after treatment with various concentrations of
      recombinant human VEGF-C (rhVEGF-C). Then, lentivirus vector-based RNA
      interference (RNAi) was used to inhibit VEGF-C expression of T24 cells. The
      alterations of T24 cells regarding proliferation, invasiveness, and the apoptosis
      induced by mitomycin C (MMC) were evaluated. The results showed that the
      proliferation rate of T24 cells rose from 27.3% to 65.0%, with increasing rhVEGF
      C concentration. T24 cells stably transfected with VEGF-C small interference RNA
      showed 85% reduction in VEGF-C mRNA expression (p < 0.05). The VEGF-C protein
      level was significantly downregulated (p < 0.05) and the growth and invasiveness
      were also inhibited (p < 0.05) compared with the control group. Further, the
      inhibition of VEGF-C expression markedly enhanced the apoptosis of T24 cells
      induced by MMC (p < 0.05). These were associated with the decreased ratio of Bcl
      2/Bax, activation of Caspase-3, decreased expression of MMP-9, as well as the
      downregulation of phosphorylated p38 MAPK and Akt. The present study suggests
      that VEGF-C can enhance the proliferation and invasiveness of bladder cancer T24
      cells, which is due to suppression of apoptosis and facilitation of migration,
      accompanied with upregulation of p38 MAPK and Akt phosphorylation. RNAi targeting
      VEGF-C could effectively suppress malignant progression and enhance
      chemosensitivity of T24 cells. Thus, inhibition of VEGF-C expression is a
      potential and promising therapeutic strategy for bladder cancer.

PMID- 21902545
TI  - Potent antitumor effect elicited by RGD-mda-7, an mda-7/IL-24 mutant, via
      targeting the integrin receptor of tumor cells.
AB  - The melanoma differentiation-associated gene-7/interleukin-24 gene (mda-7/IL-24)
      is a novel tumor-suppressor/cytokine gene that exhibits potent tumor-suppressive
      activity without damaging normal cells. To enhance the antitumor effect, an mda
      7/IL-24 mutant, RGD-mda-7, which includes the cell adhesive sequence 164Arg
      165Gly-166Asp (RGD motif), was constructed and evaluated for bioactivity. RGD
      peptide binds to integrins alpha(V)beta(3) and alpha(V)beta(5), which are
      selectively expressed in tumor neovasculature and in the surface of some tumor
      cells. The wtmda-7/IL-24 and RGD-mda-7 were expressed in Escherichia coli and
      then purified and renatured. The immunostimulatory activity of RGD-mda-7 was
      assayed by stimulating peripheral blood mononuclear cells. The results suggested
      that the abilities of RGD-mda-7 to induce IL-6, TNF-alpha, and IFN-gamma
      production were higher than wtmda-7/IL-24. Tumor targeting of RGD-mda-7 was
      assayed using cell adhesion experiments. The antitumor effect of the purified RGD
      mda-7 on cell proliferation in vitro was evaluated using 3-(4,5-dimethylthiazol-2
      yl)-2,5-diphenyltetrazolium bromide (MTT) uptake, cell apoptosis by staining with
      fluorescent probes of FITC-annexin V and DAPI, and caspase-3 expression and
      activity. The in vitro results showed that RGD-mda-7 inhibited the proliferation
      of multiple tumor cell lines (Hela, ACHN, HepG2, and A549). Staining with
      fluorescent probes of FITC-annexin V and DAPI indicated that RGD-mda-7 could
      induce apoptosis more effectively in four tumor cell lines than wtmda-7/IL-24,
      but has no effect on normal cell line NHLF. Western blotting showed that
      treatment of tumor cells with RGD-mda-7 could activate apoptotic pathway by
      cleavage of caspase-3 as same as wtmda-7/IL-24. Further, RGD-mda-7 group showed a
      higher cleaved level of caspase-3, but not in NHLF cells. These results
      demonstrate that RGD-MDA-7 possesses more potent antitumor effects than wtmda
      7/IL-24 and therefore merits further investigation in preclinical and clinical
      studies.

PMID- 21902546
TI  - The use of 125I seed strands for intraluminal brachytherapy of malignant
      obstructive jaundice.
AB  - This study is sought to evaluate the feasibility and safety of using 125I seed
      strands for intraluminal brachytherapy (ILBT) in the treatment of malignant
      obstructive jaundice (MOJ), and its clinical effect on stent patency. A total of
      34 patients found to have MOJ were randomly assigned to an ILBT treatment group
      or a control group before biliary stent insertion. For the ILBT group, 125I seed
      strands were implanted into the obstructive segment of the bile duct after stent
      insertion. For the control group, only the biliary stent was inserted. Alimentary
      and hematologic complications were examined for patients in the ILBT group. The
      stent patency of the two groups were compared. In the ILBT group, the number of
      125I seeds per strand varied from 6 to 16 (mean, 10.9), and were successfully
      implanted in 17 patients. Serum levels of bilirubin, alanine aminotransferase,
      granulocytes, and platelets assayed 2 and 4 weeks following the procedure
      demonstrated no significant difference between the ILBT group and the control
      group. The mean stent patency for ILBT group (10.2 months) was significantly
      longer than that of the control group (7.2 months, p=0.032). 125I seed strands
      for ILBT is a feasible and safe palliative therapy for the treatment of MOJ, and
      may prolong stent patency.

PMID- 21902547
TI  - The effect of loss of occlusal support on mandibular morphology in growing rats.
AB  - OBJECTIVE: To evaluate the effects of unilateral and bilateral premature loss of
      posterior occlusal support on mandibular bone dimensions in growing rats.
      MATERIALS AND METHODS: Thirty female Wistar rats (5 weeks old) were randomized
      into three groups: control, unilateral mandibular molar teeth extraction, and
      bilateral mandibular molar teeth extraction. After 8 weeks, animals were
      sacrificed and acrylic rapid-prototyped templates of the mandibles were
      constructed. Mandibular length, ramus height, intercondylar distance, and body
      weight were measured and analyzed by one-way analysis of variance (Tukey test as
      post hoc test; alpha  =  .05). RESULTS: Mandibular length and intercondylar
      distance were significantly shorter in experimental animals, while no difference
      was observed for ramus height and body weight. CONCLUSIONS: Unilateral and
      bilateral premature loss of posterior occlusal support in growing rats results in
      a smaller mandible at skeletal maturity.

PMID- 21902549
TI  - Therapeutic application of 6-Hz-primed low-frequency rTMS combined with intensive
      speech therapy for post-stroke aphasia.
AB  - OBJECTIVE: To clarify the safety, feasibility and efficacy of 6-Hz-primed low
      frequency repetitive transcranial magnetic stimulation (rTMS) combined with
      intensive speech therapy (ST) for post-stroke aphasic patients. METHODS: Four
      adult patients with history of left hemispheric stroke and with motor-dominant
      aphasia were studied. During 11-day hospitalization, each patient received 18
      treatment sessions consisting of 10-min 6-Hz priming stimulation followed by 20
      min 1-Hz low-frequency rTMS and intensive ST for 60 min daily. Both the priming
      stimulation and low-frequency rTMS were applied to the right frontal lobe. The
      intensive ST was provided on one-to-one basis. Language function was assessed by
      Standard Language Test of Aphasia (SLTA), Supplementary Test of SLTA (SLTA-ST),
      and the Japanese version of Western Aphasia Battery (WAB) within 2 weeks prior to
      the admission and on the day of discharge. RESULTS: The in-patient protocol was
      successfully completed by all patients without any adverse effects. Each patient
      showed an increase in the correct answer rate after the intervention. Improvement
      was found in both expressive and recessive language modalities in all patients.
      CONCLUSIONS: The protocol of 6-Hz-primed low-frequency rTMS and intensive ST for
      post-stroke aphasia was safe and feasible, suggesting its potential usefulness in
      the treatment of this population.

PMID- 21902548
TI  - Emerging roles for the interferon-inducible p200-family proteins in sex bias in
      systemic lupus erythematosus.
AB  - Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving
      multiple organs. The disease is characterized by the production of pathogenic
      autoantibodies to DNA and certain nuclear antigens, chronic inflammation, and
      immune dysregulation. Genetic studies involving SLE patients and mouse models
      have indicated that multiple lupus susceptible genes contribute to the disease
      phenotype. Notably, the development of SLE in patients and in certain mouse
      models exhibits a strong sex bias. In addition, several lines of evidence
      indicates that activation of interferon-alpha (IFN-alpha) signaling in immune
      cells and alterations in the expression of certain immunomodulatory cytokines
      contribute to lupus pathogenesis. Studies have implicated factors, such as the X
      chromosomal gene dosage effect and the sex hormones, in gender bias in SLE.
      However, the molecular mechanisms remain unclear. Additionally, it remains
      unclear whether these factors influence the "IFN-signature," which is associated
      with SLE. In this regard, a mutually positive regulatory feedback loop between
      IFNs and estrogen receptor-alpha (ERalpha) has been identified in immune cells.
      Moreover, studies indicate that the expression of certain IFN-inducible p200
      family proteins that act as innate immune sensors for cytosolic DNA is
      differentially regulated by sex hormones. In this review, we discuss how the
      modulation of the expression of the p200-family proteins in immune cells by sex
      hormones and IFNs contributes to sex bias in SLE. An improved understanding of
      the regulation and roles of the p200-family proteins in immune cells is critical
      to understand lupus pathogenesis as well as response (or the lack of it) to
      various therapies.

PMID- 21902550
TI  - A prospective study of early versus late craniectomy after traumatic brain
      injury.
AB  - BACKGROUND: Decompressive craniectomy is an important method for managing
      traumatic brain injury (TBI). At present, controversies about this procedure
      exist, especially about the optimum operative time for patients with TBI.
      METHODS: A prospective study was performed at the First Affiliated Hospital,
      College of Medicine, Zhejiang University. From January 2008 to December 2009, 25
      patients who underwent early decompressive craniectomy were included in the study
      group, and 19 patients who underwent "late" decompressive craniectomy as a second
      tier therapy for intracranial hypertension were included as a comparison group.
      RESULTS: The 30-day mortality after the operation was 16% in the study group. The
      overall mortality rate was 20% at the 6-month follow-up. A total of 52% of the
      patients (13 patients) had good outcomes, and 7 patients remained in a severely
      disabled or vegetative state. In the comparison group, 4 patients died, and 12
      had good outcomes at the 6-month follow-up. The remaining 3 patients had poor
      outcomes. The study group was well matched with the comparison group. However,
      the outcomes in the study group were not better than those in the comparison
      group, as evaluated by the 6-month GOS score. CONCLUSION: Early decompressive
      craniectomy as a first-tier therapy for intracranial hypertension did not improve
      patient outcome when compared with "late" decompressive craniectomy for managing
      TBI.

PMID- 21902551
TI  - Validation of the Abbreviated Westmead Post-traumatic Amnesia Scale: a brief
      measure to identify acute cognitive impairment in mild traumatic brain injury.
AB  - OBJECTIVE: To validate the use of the Abbreviated Westmead Post-traumatic Amnesia
      Scale (A-WPTAS) in the assessment of acute cognitive impairment in mild traumatic
      brain injury (mTBI). METHODS: Data previously collected from 82 mTBI and 88
      control participants using the Revised Westmead Post-traumatic Amnesia Scale (R
      WPTAS) was converted to A-WPTAS scores and pass/fail classifications were
      calculated for both scales. RESULTS: The proportion of failures on the R-WPTAS
      and the A-WPTAS did not differ and a similar number of mTBIs were classified on
      each. For mTBIs the relationship between the independent memory test and a
      pass/fail classification was the same for both scales. Bivariate logistic
      regressions revealed that mTBIs, relative to controls, were around 8 times more
      likely to fail the assessment (R-WPTAS: 95% CI: 3.70-18.87; A-WPTAS: 95% CI: 3.70
      20.14). As verbal learning improved the likelihood of failure was reduced.
      Greater education was associated with a decreased likelihood of failure. The
      relationship between education and a fail performance was not sustained when
      education was adjusted for the effect of age, prior mTBI, blood alcohol level,
      injury status, verbal learning, and morphine administration. CONCLUSIONS: The A
      WPTAS is a valid measure. The A-WPTAS may reduce the risk of failing to classify
      patients with mTBI by identifying and documenting acute cognitive impairment.

PMID- 21902552
TI  - Relationship of soccer heading to computerized neurocognitive performance and
      symptoms among female and male youth soccer players.
AB  - PRIMARY OBJECTIVE: The purpose of this study was to investigate the relationship
      between soccer heading and computerized neurocognitive performance and symptoms
      in female and male youth soccer players. RESEARCH DESIGN: Cross-sectional and
      prospective design. METHODS AND PROCEDURES: A total of 63 (27 females, 36 males)
      youth soccer players aged 13-18 years (M = 15.89, SD = 1.17) participated in the
      study. Participants completed the Immediate Post-concussion Assessment and
      Cognitive Test (ImPACT) and symptom report. MAIN OUTCOMES: Computerized
      neurocognitive performance (e.g., verbal and visual memory, motor processing, and
      reaction time) and symptoms. RESULTS: There were no differences in neurocognitive
      performance or symptoms among low-, moderate-, and high-exposure header groups.
      The current sample outperformed the 10th percentile norms for neurocognitive and
      symptom scores. Males headed the ball more frequently and reported lower verbal
      and visual memory and motor processing speed scores than females. CONCLUSION: The
      current findings did not support a relationship between soccer heading and
      computerized neurocognitive performance and symptoms. The researchers suggest
      that any purported effects of soccer heading in youth are subtle and may affect
      only a small number of athletes. The reported sex differences in heading exposure
      warrant further attention.

PMID- 21902554
TI  - Simultaneous analysis of free and sulfo-conjugated steroid estrogens in
      artificial urine solution and agricultural soils by high-performance liquid
      chromatography.
AB  - A simple and robust analytical method was developed to simultaneously detect and
      quantify 17beta-estradiol (E2), estrone (E1), 17beta-estradiol-3-sulphate (E2
      3S), and estrone-3-sulphate (E1-3S) in aqueous solutions (calcium chloride and
      artificial urine solutions) and agricultural soils using high performance liquid
      chromatography and UV detection. The standards for all four compounds were linear
      in the range of 0.01 to 1.0 MUg mL(-1) (n = 6) and 1.0 to 20 MUg mL(-1) (n = 6),
      respectively, with correlation coefficients > 0.999. The on-column limits of
      detection at an injection volume of 50 MUL and S/N (signal: noise) ratio of 3
      were: 9.0 ng mL(-1), 10 ng mL(-1), 5.0 ng mL(-1), and 7.0 ng mL(-1) for E2-3S, E1
      3S, E2 and E1, respectively. The limit of detection and quantification in
      artificial urine solution and CaCl(2) solution was 1.0 ng mL(-1) for all four
      compounds. Method detection limits for the compounds in the 3 soils ranged from 2
      to 2.4 ng g(-1) (E2-3S and E1-3S), and 1.0 to 2.9 ng g(-1) (E2 and E1),
      respectively.

PMID- 21902555
TI  - Does malaoxon play a role in the geno- and cytotoxic effects of malathion on
      human choriocarcinoma cells?
AB  - This investigation was undertaken to elucidate whether the active metabolite of
      malathion, malaoxon, has any role in exerting cyto- and genotoxic effects for
      human choriocarcinoma (JAR) cell line which is an acceptable model for human
      placental cells. Gas chromatography-mass spectrometry (GC-MS) analysis were
      separately performed on the cell compartment and supernatant cell culture medium
      after subjecting the cell line to different malathion concentrations (10-400
      MUg/mL) and for various incubation periods (0.5 to 24 hours). GC-MS analysis
      showed that the sonication performed for the disruption of the cells did not
      cause the chemical change of malathion. The uptake of malathion by the cells was
      relatively fast. However, the presence of malaoxon, even in trace amounts, could
      not be confirmed either in samples originating from disrupted cells or in the
      cell culture medium. Although the hydrolysis of malaoxon occurred in the culture
      medium, this degradation process could not be counted as a reason for the absence
      of malaoxon. Since both malathion and malaoxon standard compounds could be
      accurately detected and distinguished by the applied liquid-liquid extraction and
      GC-MS methods, one can conclude that, in the case of JAR cells, the parent
      compound, (i.e. malathion itself) is responsible for the observed in vitro cyto-
      and genotoxic effects. Our results indicate that the direct toxicity of malathion
      contributes to the complications of pregnancy observed for environmental
      malathion exposure.

PMID- 21902556
TI  - Pesticide exposure and serum organochlorine residuals among testicular cancer
      patients and healthy controls.
AB  - The incidence of testicular cancer (TC) has been increasing worldwide during the
      last decades. The reasons of the increase remains unknown, but recent findings
      suggest that organochlorine pesticides (OPs) could influence the development of
      TC. A hospital-based case-control study of 50 cases and 48 controls was conducted
      to determine whether environmental exposure to OPs is associated with the risk of
      TC, and by measuring serum concentrations of OPs, including p,p'
      dichlorodiphenyldichloroethylene (p,p'-DDE) isomer and hexachlorobenzene (HCB) in
      participants. A significant association was observed between TC and household
      insecticide use (odds ratio [OR] = 3.01, 95 % CI: 1.11-8.14; OR(adjusted) = 3.23,
      95 % CI: 1.15-9.11). Crude and adjusted ORs for TC were also significantly
      associated with higher serum concentrations of total OPs (OR = 3.15, 95 % CI:
      1.00-9.91; OR(adjusted) = 3.34, 95 % CI: 1.09-10.17) in cases compared with
      controls. These findings give additional support to the results of previous
      research that suggest that some environmental exposures to OPs may be implicated
      in the pathogenesis of TC.

PMID- 21902557
TI  - Structural alterations in rabbit spleen after bendiocarb administration.
AB  - The histological structure of rabbit spleen after bendiocarb administration was
      studied. Bendiocarb was perorally administered for 30 days. At day 10, 20 and 30
      morphometric analysis was realized. Quantitative evaluation showed that in the
      control group the relative spleen volume of white pulp ranged from 35.03 +/-
      10.94 % and the relative volume of red pulp 64.97 +/- 10.94 %. In all
      experimental groups were detected significantly higher relative volume of red
      pulp and the lower relative volume of white pulp, except on day 30. The
      experimental groups showed a significant increase in the number of lymphocytes in
      comparison with the control group. On day 10 we observed a significant increase
      in diameter of investigated lymphocytes. The results of our study determined
      structural alterations in spleen structure after bendiocarb administration, which
      probably causes alteration in the immune system.

PMID- 21902558
TI  - Development and initial validation of the Therapeutic Misunderstanding Scale for
      use with clinical trials research participants.
AB  - Therapeutic misconception is evident when clinical trials participants conflate
      research and treatment, erroneously believing that every aspect of the research
      is intended to be for their direct benefit. We developed the 20-item Therapeutic
      Misunderstanding Scale (TMU) based on responses from 464 community-dwelling
      adults 50+ years of age (Study 1). A three-factor solution based on Horng and
      Grady's (2003) three-facets definition was identified using both exploratory and
      confirmatory factor analyses (EFA and CFA; these analyses were performed on
      separate samples). CFA results point to a second-order solution where each of
      Horng and Grady's three facets contribute significantly to the measurement of a
      higher-order therapeutic misunderstanding latent construct. Internal consistency
      of TMU responses (full scale) as well as the therapeutic misconception,
      misestimation, and optimism subscales were calculated as alpha = 0.88, alpha =
      0.83, alpha = 0.79, and alpha = 0.75, respectively. These results were
      subsequently supported with responses from former clinical trials participants
      (Study 2). This TMU provides applied researchers a brief measure for use in
      future studies as well as a screening instrument for clinicians to more fully
      assess informed consent for participation in clinical trials research.

PMID- 21902559
TI  - Individual and community-level tolerance of spouse abuse and the association with
      the circumstances of first sex among youth from six sub-Saharan African
      countries.
AB  - Youth who engage in early and premarital sex are at risk of HIV and sexually
      transmitted infections. Most prevention programs ignore the mediating influence
      of the threat and experience of violence on these outcomes. Using nationally
      representative data from Lesotho, Malawi, Zimbabwe, Kenya, Tanzania, and Uganda,
      multivariate analyses examined the association between individual- and community
      level tolerance of spouse abuse on the age and circumstances of sexual debut
      among female youth. The youth sample sizes ranged from a high of 5007 in Malawi
      to a low of 3050 in Lesotho. In the study countries, there were between 521 and
      367 communities included in the analysis. Youth who approved of spouse abuse were
      more likely to have sexually debuted at each age. In Kenya, youth from
      communities with high female spouse abuse tolerance were more likely to have
      initiated sex at each age. In Malawi and Zimbabwe, youth from high tolerance
      communities were less likely to have sexually debuted at each age or to have had
      premarital sex; the same effect on premarital sex was found for men's tolerance
      in Kenya and Tanzania. Programs are needed to reduce violence risk and increase
      youth negotiating power and delayed sexual debut, with the objective of reducing
      young people's risk of negative outcomes.

PMID- 21902560
TI  - Chronic depressive symptoms and Framingham coronary risk in HIV-infected and HIV
      uninfected women.
AB  - Depression is common in people with cardiovascular diseases (CVD) and those with
      HIV, and is a risk factor for CVD-related mortality. However, little is known
      about whether HIV influences the relationship between depression and
      cardiovascular risk. A total of 526 HIV-infected and 132 uninfected women from
      the Women's Interagency HIV Study were included in an analysis of women who
      completed twice-yearly study visits over 9.5 years. CVD risk was calculated at
      baseline and approximately 9.5 years later using the Framingham Risk Score (FRS).
      Chronic depressive symptoms were defined as Center for Epidemiologic Studies
      Depression Scale scores of 16 or greater at >=75% of study visits. Over the
      follow-up period, 22.8% of HIV-infected women and 15.9% of HIV-uninfected women
      had chronic depressive symptoms (p=0.08). Baseline FRS was similar between HIV
      infected and uninfected women (M=-5.70 +/- SE=0.30 vs. M=-6.90 +/- SE=0.60,
      p=0.07) as was follow-up FRS (M=0.82 +/- SE=0.30 vs. M=-0.44 +/- SE=0.73,
      p=0.11). Among HIV-infected and HIV-uninfected women, together, follow-up FRS was
      higher among women with chronic depressive symptoms as compared to those without
      (M=1.3 +/- SE=0.6 vs. M=-0.3 +/- SE=0.40, p<0.01), after adjusting for baseline
      FRS and other covariates. HIV status did not modify the relationship between
      chronic depressive symptoms and FRS. Chronic depressive symptoms accelerated CVD
      risk scores to a similar extent in both HIV-infected and-uninfected women. This
      implies that the diagnosis and treatment of depression may be an important
      consideration in CV risk reduction in the setting of HIV-infection. The
      determination of factors that mediate the depression/CVD relationship merits
      further study.

PMID- 21902561
TI  - Prevalence and correlates of alcohol use among a sample of general MSM and money
      boys in Shanghai, China.
AB  - The use and misuse of alcohol and their relation to risky sex have received
      modest scholarly attention in China. This type of research in high HIV/STI groups
      such as men who have sex with men (general MSM) and men who sell sex to other men
      ("money boys") (MB) in China is essentially absent. Therefore, the primary
      purpose of this exploratory study was to describe the types of alcohol consumed
      and levels of daily alcohol consumption among Chinese general MSM and MB in
      Shanghai, China. A secondary purpose was to explore demographic, lifetime sexual
      behavior, and psychosocial correlates of daily consumption levels. The sample
      consisted of 404 MSM (200 MB) who live in Shanghai, China. Participants were
      recruited using respondent-driven sampling and filled out a cross-sectional
      behavioral survey. Where appropriate, comparisons were made between MB and
      general MSM. Over 73% of participants reported drinking at least moderately every
      day. MB reported drinking Western red wine and other Western hard liquors (e.g.,
      vodka) more frequently than general MSM. Conversely, general MSM consumed Chinese
      white wine more frequently than MB. Results from the regression analyses showed
      that MSM having higher lifetime sexual risks were more likely to drink in excess;
      though MB with greater social provisions were less likely to drink in excess.
      These results begin to highlight high levels of drinking and drinking-sexual risk
      relationships among groups of general MSM and MB and are useful for guiding
      intervention efforts among high-risk groups in China.

PMID- 21902562
TI  - Allicin induces apoptosis in EL-4 cells in vitro by activation of expression of
      caspase-3 and -12 and up-regulation of the ratio of Bax/Bcl-2.
AB  - Garlic (Allium sativum L.; Liliaceae) has been widely demonstrated in the role of
      cancer prevention, but the specific compound in garlic corresponding to this
      effect and its mechanisms are not clearly known. Allicin is one of the organic
      sulphur compounds derived from garlic. In the present study we investigated the
      anti-proliferative and pro-apoptotic activities of allicin in murine T
      lymphocytes (EL-4) and the mechanism of inducing apoptosis in vitro. The results
      showed that allicin was effective in inhibiting the proliferation of EL-4 cells
      in vitro in a concentration-dependent manner. Further, allicin could induce the
      formation of apoptotic bodies, nuclear condensation, DNA spallation, and even
      activated the expression of caspase-3, -12 and cytochrome C (cyt C). Finally,
      allicin up-regulated the ratio of Bax/Bcl-2 and induced a mitochondrion membrane
      potential (MMP) decrease. Allicin induced apoptosis in EL-4 cells in a time- and
      concentration-dependent manner, in which the mitochondrial pathway might play a
      central role.

PMID- 21902563
TI  - Antifungal activity and chemical composition of essential oils from Smyrnium
      olusatrum L. (Apiaceae) from Italy and Portugal.
AB  - The essential oils and supercritical CO2 extracts of wild Smyrnium olusatrum L.
      growing in Sardinia (Italy) and in Portugal were investigated. For the study,
      oils were isolated from total plant aerial part (umbels containing seeds). The
      content of beta-phellandrene (67.3% vs. 42.7%) and alpha-pinene (31.9% vs. 1.2%),
      respectively, the main components of Portuguese and Italian essential oils,
      declined during the maturation stage of the umbels. Contrarily, some other
      important components, particularly curzerene, germacrene B, germacrone,
      alexandrofuran, 1-beta-acetoxyfurano-4(15)-eudesmene and 1-beta-acetoxyfurano-3
      eudesmene, increased in fruiting umbels. The chemical composition of the
      Sardinian oil is rather different from those of other origin. The composition of
      the supercritical extracts and the essential oils is markedly different,
      particularly due to the high amount of furanosesquiterpenoids in the
      supercritical fluid extraction. The minimal inhibitory concentration (MIC) and
      the minimal lethal concentration were used to evaluate the antifungal activity of
      the oils against Candida albicans, Candida tropicalis, Candida krusei, Candida
      guillermondii, Candida parapsilosis, Cryptococcus neoformans, Trichophyton
      rubrum, Trichophyton mentagrophytes, Microsporum canis, Microsporum gypseum,
      Epidermophyton floccosum, Aspergillus niger, Aspergillus fumigatus and
      Aspergillus flavus. The oils were particularly active against dermatophyte
      strains and C. neoformans, with MIC values in the range of 0.32-0.64 uL mL-1.

PMID- 21902565
TI  - A comparison of selected MMPI-2 and MMPI-2-RF validity scales in assessing effort
      on cognitive tests in a military sample.
AB  - Using a relatively new statistical paradigm, Optimal Data Analysis (ODA; Yarnold
      & Soltysik, 2005), this research demonstrated that newly developed scales for the
      Minnesota Multiphasic Personality Inventory-2 (MMPI-2) and MMPI-2 Restructured
      Form (MMPI-2-RF) specifically designed to assess over-reporting of cognitive
      and/or somatic symptoms were more effective than the MMPI-2 F-family of scales in
      predicting effort status on tests of cognitive functioning in a sample of 288
      military members. ODA demonstrated that when all scales were performing at their
      theoretical maximum possible level of classification accuracy, the Henry
      Heilbronner Index (HHI), Response Bias Scale (RBS), Fake Bad Scale (FBS), and the
      Symptom Validity Scale (FBS-r) outperformed the F-family of scales on a variety
      of ODA indexes of classification accuracy, including an omnibus measure (effect
      strength total, EST) of the descriptive and prognostic utility of ODA models
      developed for each scale. Based on the guidelines suggested by Yarnold and
      Soltysik for evaluating effect strengths for ODA models, the newly developed
      scales had effects sizes that were moderate in size (37.66 to 45.68), whereas the
      F-family scales had effects strengths that ranged from weak to moderate (15.42 to
      32.80). In addition, traditional analysis demonstrated that HHI, RBS, FBS, and
      FBS-R had large effect sizes (0.98 to 1.16) based on Cohen's (1988) suggested
      categorization of effect size when comparing mean scores for adequate versus
      inadequate effort groups, whereas F-family of scales had small to medium effect
      sizes (0.25 to 0.76). The MMPI-2-RF Infrequent Somatic Responses Scale (F(S))
      tended to perform in a fashion similar to F, the best performing F-family scale.

PMID- 21902564
TI  - Challenges and opportunities for genomic developmental neuropsychology: examples
      from the Penn-Drexel collaborative battery.
AB  - Genomics has been revolutionizing medicine over the past decade by offering
      mechanistic insights into disease processes and engendering the age of
      "individualized medicine." Because of the sheer number of measures generated by
      gene sequencing methods, genomics requires "Big Science" where large datasets on
      genes are analyzed in reference to electronic medical record data. This
      revolution has largely bypassed the behavioral neurosciences, mainly because of
      the paucity of behavioral data in medical records and the labor-intensity of
      available neuropsychological assessment methods. We describe the development and
      implementation of an efficient neuroscience-based computerized battery, coupled
      with a computerized clinical assessment procedure. This assessment package has
      been applied to a genomic study of 10,000 children aged 8-21, of whom 1000 also
      undergo neuroimaging. Results from the first 3000 participants indicate
      sensitivity to neurodevelopmental trajectories. Sex differences were evident,
      with females outperforming males in memory and social cognition domains, while
      for spatial processing males were more accurate and faster, and they were faster
      on simple motor tasks. The study illustrates what will hopefully become a major
      component of the work of clinical and research neuropsychologists as invaluable
      participants in the dawning age of Big Science neuropsychological genomics.

PMID- 21902566
TI  - Neurocognitive decline in Alexander disease.
AB  - Alexander disease is a neurological condition associated with prominent white
      matter deterioration. Its rarity and relatively rapid disease course have
      provided limited understanding into the cognitive effects of the illness. We
      report the serial neuropsychological findings of a 21-year-old with normal
      development and no medical history until age 9, when he experienced refractory
      sinusitis, stabbing headaches with vertigo, disorientation, and decline in
      academic and social settings. An MRI scan of the brain found acute demyelinating
      encephalomyelitis, with a preponderance of white matter degeneration in the
      bilateral frontal lobes. Interval MRIs showed continued degeneration.
      Confirmation of Alexander disease was made at age 20 through genetic testing.
      Four evaluations completed from ages 15 to 21 showed impairment across all
      cognitive domains. Cognitive deficits were most prominent in new learning and
      recent memory, executive functions, and fine motor dexterity, and less apparent
      in information processing and visual scanning speed. These results present
      evidence for a particular cognitive pattern in individuals with juvenile-onset
      Alexander disease. Despite extensive white matter degeneration in the frontal
      lobes, certain tasks associated with frontal lobe integrity were relatively
      preserved. Further research into the neuropsychological presentation of the
      subtypes of Alexander disease can enhance diagnostic clarity and treatment
      planning.

PMID- 21902567
TI  - Emotion regulation through listening to music in everyday situations.
AB  - Music is a stimulus capable of triggering an array of basic and complex emotions.
      We investigated whether and how individuals employ music to induce specific
      emotional states in everyday situations for the purpose of emotion regulation.
      Furthermore, we wanted to examine whether specific emotion-regulation styles
      influence music selection in specific situations. Participants indicated how
      likely it would be that they would want to listen to various pieces of music
      (which are known to elicit specific emotions) in various emotional situations.
      Data analyses by means of non-metric multidimensional scaling revealed a clear
      preference for pieces of music that were emotionally congruent with an emotional
      situation. In addition, we found that specific emotion-regulation styles might
      influence the selection of pieces of music characterised by specific emotions.
      Our findings demonstrate emotion-congruent music selection and highlight the
      important role of specific emotion-regulation styles in the selection of music in
      everyday situations.

PMID- 21902568
TI  - Neuropsychological and behavioral measures of attention assess different
      constructs in children with traumatic brain injury.
AB  - Neuropsychological and behavioral measures are used to assess attention, but
      little convergence has been found between these two assessment methods. However,
      many prior studies have not considered attention as a multicomponent system,
      which may contribute to this lack of agreement between neuropsychological and
      behavioral measures. To address this the current study examined the relationship
      between the neuropsychological measures that comprise a four-component model of
      attention and parent-report behavioral ratings of attention problems and
      hyperactivity. A total of 65 children and adolescents who had sustained a
      traumatic brain injury (TBI) were included in the study. Principal components
      analysis identified the four attention components in this sample, which accounted
      for 80.9% of the variance. However, correlations between the neuropsychological
      measures of attention and behavioral ratings of attention and hyperactivity were
      low and non-significant. This minimal correspondence suggests that
      neuropsychological and behavioral measures assess different aspects of
      attentional disturbances in children with TBI.

PMID- 21902569
TI  - Antimicrobial activity and a comparative essential oil analysis of Centaurea
      pulcherrima Willd. var. pulcherrima extracted by hydrodistillation and microwave
      distillation.
AB  - The essential oils of Centaurea pulcherrima Willd. var. pulcherrima (Asteraceae)
      were isolated by hydrodistillation (HD) and a microwave distillation (MD), than
      characterised by GC-FID and GC-MS. A total of 58 and 57 compounds were
      identified, constituting over 93.7%, and 91.6% of volatile oil composition of C.
      pulcherrima var. pulcherrima, respectively. Sesquiterpene hydrocarbons were shown
      to be the main group of constituents (HD: 42.4% versus MD: 51.5%). The major
      component of the oils of C. pulcherrima var. pulcherrima was germacrene D (HD,
      17.8% versus MD, 23.2%). The antimicrobial activity of the isolated essential
      oils of the plant was also investigated, and they showed good antibacterial
      activity against to tested gram-positive bacteria, especially to M. smegmatis and
      a yeast-like fungus C. albicans.

PMID- 21902570
TI  - HIV disclosure patterns, predictors, and psychosocial correlates among HIV
      positive women in Zimbabwe.
AB  - Disclosure of positive HIV status in Sub-Saharan Africa has been associated with
      safer sexual practices and better antiretroviral therapy (ART) adherence, but
      associations with psychosocial function are unclear. We examined patterns and
      psychosocial correlates of disclosure in a Zimbabwean community. Two hundred HIV
      positive women at different stages of initiating ART participated in a cross
      sectional study examining actual disclosures, disclosure beliefs, perceived
      stigma, self-esteem, depression, and quality of life. Ninety-seven percent of the
      women disclosed to at least one person, 78% disclosed to their current
      husband/partner, with an average disclosure of four persons per woman. The
      majority (85-98%) of disclosures occurred in a positive manner and 72-95% of the
      individuals reacted positively. Factors significantly correlated with HIV
      disclosure to partners included being married, later age at menses, longer
      duration of HIV since diagnosis, being on ART, being more symptomatic at
      baseline, ever having used condoms, and greater number of partners in the last
      year. In multivariate analysis, being married and age at menses predicted
      disclosure to partners. Positive disclosure beliefs, but not the total number of
      disclosures, significantly correlated with lower perceived stigma (rho = 0.44 for
      personalized subscale and rho = 0.51 for public subscale, both p<0.0001), higher
      self-esteem (rho = 0.15, p=0.04), and fewer depressive symptoms (rho = -0.14,
      p=0.05). In conclusion, disclosure of positive HIV status among Zimbabwean women
      is common and is frequently met with positive reactions. Moreover, positive
      disclosure beliefs correlate significantly with psychosocial measures, including
      lower perceived stigma, higher self-esteem, and lower depression.

PMID- 21902571
TI  - Factors associated with HIV among female sex workers in a high HIV prevalent
      state of India.
AB  - The study was carried out to assess the factors associated with HIV
      seropositivity among female sex workers (FSWs) in Dimapur, Nagaland, a high HIV
      prevalence state of India. A total of 426 FSWs were recruited into the study
      using respondent driven sampling (RDS). Data on demographic characteristics,
      sexual and injecting risk behaviours were collected from them and were tested for
      HIV, Syphilis, Neisseria gonorrhoeae and Chlamydia trachomatis. RDS-weighted
      univariate and multivariate logistic regression analysis was performed to assess
      the factors associated with HIV seropositivity. Consistent condom use with
      regular and occasional sexual clients was 9% and 16.4%, respectively. About 25%
      of the participants ever used and 5.7% ever injected illicit drugs. RDS adjusted
      HIV prevalence was 11.6%. In the univariate analysis, factors associated with HIV
      were initiating sexual intercourse before the age of 15 years, >=2 years duration
      of sex work, serving clients at lodge/hotel, positive test result for one or more
      sexually transmitted infections (STIs), lifetime history of injecting drug use,
      lifetime history of consuming illicit drugs, ever having exchanged sex for drugs,
      having sexual partners who engaged in risky injecting practices and having been
      widowed or divorced. In multivariate analysis, factors found to be independently
      associated with HIV included lifetime injecting drug use, initiating sexual
      intercourse before the age of 15 years, positive test result for one or more STIs
      and having been widowed. Injecting drug use was found to be most potent
      independent risk factor for HIV (OR: 3.17, CI: 1.02-9.89). Because of lower
      consistent condom use among them, FSWs may act as bridge for HIV transmission to
      general population from injecting drug users (IDU) through their sexual clients.
      The informations from this study may be useful for enriching the HIV preventions
      effort for FSWs in this region.

PMID- 21902572
TI  - Measuring the speed of recognising facially expressed emotions.
AB  - Faces provide identity- and emotion-related information-basic cues for mastering
      social interactions. Traditional models of face recognition suggest that
      following a very first initial stage the processing streams for facial identity
      and expression depart. In the present study we extended our previous multivariate
      investigations of face identity processing abilities to the speed of recognising
      facially expressed emotions. Analyses are based on a sample of N=151 young
      adults. First, we established a measurement model with a higher order factor for
      the speed of recognising facially expressed emotions (SRE). This model has
      acceptable fit without specifying emotion-specific relations between indicators.
      Next, we assessed whether SRE can be reliably distinguished from the speed of
      recognising facial identity (SRI) and found latent factors for SRE and SRI to be
      perfectly correlated. In contrast, SRE and SRI were both only moderately related
      to a latent factor for the speed of recognising non-face stimuli (SRNF). We
      conclude that the processing of facial stimuli-and not the processing of facially
      expressed basic emotions-is the critical component of SRE. These findings are at
      variance with suggestions of separate routes for processing facial identity and
      emotional facial expressions and suggest much more communality between these
      streams as far as the aspect of processing speed is concerned.

PMID- 21902573
TI  - Simultaneous determination of cyclophosphamide and 4-hydroxycyclophosphamide in
      human plasma by high-performance liquid chromatography coupled with electrospray
      ionization tandem mass spectrometry - application to Chinese systemic lupus
      erythematosus patients.
AB  - BACKGROUND: A pharmacogenomics study of cyclophosphamide in systemic lupus
      erythematosus patients is being conducted in our laboratory in which the plasma
      concentrations of cyclophosphamide and its active metabolite 4
      hydroxycyclophosphamide should be assayed rapidly and sensitively. METHODS: A
      rapid, stable and sensitive liquid chromato-graphy/electrospray ionization tandem
      mass spectrometry method was developed to simultaneously determine
      cyclophosphamide and 4-hydroxycyclophosphamide in human plasma with ifosfomide as
      an internal standard. After a protein precipitation with cold acetonitrile and
      stabilization of 4-hydroxycyclophosphamide by ansyldrazine and extraction with
      ethyl acetate, separation was performed on a C18 3.5 MUm 2.1 * 50 mm column with
      mobile phase of acetonitrile and water (50:50, v/v) with 0.1% formic acid at 200
      MUL/min. The chromatographic run time was 3 min. RESULTS: The linear calibration
      curves ranged from 5 to 5000 ng/mL for cyclophosphamide and 5-500 ng/mL for 4
      hydroxycyclophosphamide. The recoveries of the liquid extraction were 54.5%-58.5%
      for cyclophosphamide and 103.5%-105.5% for 4-hydroxycyclophosphamide. The lower
      limit of quantification was 5 ng/mL for both analytes. The intra- and inter-day
      precision was <15% for quality control samples at 4000, 500, 50 ng/mL for
      cyclophosphamide and 4-hydroxycyclophosphamide at 400, 100, 20 ng/mL. The method
      was applied in this pharmacogenomics study in Chinese systemic lupus
      erythematosus patients treated with low-dose cyclophosphamide. CONCLUSIONS: The
      method was efficient with shorter running time and lower limit of quantification
      compared to previous reports and has been successfully applied in this
      pharmacogenomics study.

PMID- 21902574
TI  - Correlation of cortisol in 1-cm hair segment with salivary cortisol in human:
      hair cortisol as an endogenous biomarker.
AB  - BACKGROUND: Cortisol level in human hair would be an endogenous biomarker for the
      retrospective assessment of long-term central hypothalamo-pituitary-adrenal
      activity. However, no direct evidence supports that blood-related diffusion is a
      biologically endogenous source of hair cortisol in humans. The present study aims
      to validate the direct correlation between cortisol in 1-cm hair segments and
      salivary cortisol in healthy humans. METHODS: We collected three saliva samples
      from the same participant at Time 1, Time 2 (1 week later) and Time 3 (2 weeks
      later), and hair 4 weeks later. Cortisol levels in 1-cm hair segments and saliva
      were determined with high performance liquid chromatography tandem mass
      spectrometry. RESULTS: Salivary cortisol at Time 1 was significantly associated
      with that at Time 2 (r=0.514, p=0.003), but not with that at Time 3 (r=0.187,
      p=0.305); and the one at Time 2 was significantly associated with that at Time 3
      (r=0.380, p=0.032). Hair cortisol was significantly correlated with salivary
      cortisol at Time 2 (r=0.389, p<0.05) and average salivary cortisol (r=0.383,
      p<0.05) from three sampling. CONCLUSIONS: Our results confirmed that blood
      related diffusion mechanism is a biologically endogenous source of hair cortisol.

PMID- 21902575
TI  - Genetic variants in miR-146a, miR-149, miR-196a2, miR-499 and their influence on
      relative expression in lung cancers.
AB  - BACKGROUND: The presence of sequence variants in miRNA genes may influence their
      processing, expression and binding to target mRNAs. Since single miRNA can have a
      large number of potential mRNA targets, even minor variations in its expression
      can have influences on hundreds of putative mRNAs. METHODS: Here, we evaluated
      101 paired samples (cancer and normal tissues) from non-small cell lung carcinoma
      (NSCLC) patients to study the genotype distribution of single nucleotide
      polymorphisms (SNPs) in miR-146a (rs2910164 C-G), miR-149 (rs2292832 C-T), miR
      196a2 (rs11614913 C-T) and miR-499 (rs3746444 G-A) and their influence on the
      expression of respective miRNAs. RESULTS: Relative expression of miR-146a, miR
      149 and miR-499 were comparable in NSCLC and in paired control tissues. On the
      contrary, we clearly detected a significant increase (p<0.001) of miR-196a2
      expression in NSCLC. In particular we found a significant association between miR
      196a2 CC genotype and high expression, whereas TT geno-type showed a very low
      expression in comparison to both CT (p<0.005) and CC patients (p<0.01). We did
      not find any association between miR-149, miR-196a2 and miR-499 genotype and risk
      of NSCLC. Conversely, CG genotype of miR-146a appeared associated to an increased
      risk for NSCLC (p=0.042 and 1.77 OR). CONCLUSIONS: Our results seem to
      demonstrate that sequence variants of miR-196a2 can have an influence on its
      expression, while miR-146a can have a role in increasing the risk of NSCLC.

PMID- 21902576
TI  - Genetic alterations in members of the Wnt pathway in acute leukemia.

PMID- 21902577
TI  - Lenalidomide: a new treatment option for Castleman disease.

PMID- 21902579
TI  - Mercaptopurine-induced hypersensitivity febrile reaction in patient with acute
      promyelocytic leukemia.

PMID- 21902578
TI  - Interleukin-6 plasma levels are modulated by a polymorphism in the NF-kappaB1
      gene and are associated with outcome following rituximab-combined chemotherapy in
      diffuse large B-cell non-Hodgkin lymphoma.
AB  - Peripheral blood cytokines are known prognostic parameters in diffuse large B
      cell lymphoma (DLBCL) treated with chemotherapy, but their role after the
      introduction of rituximab is unknown. Seven polymorphisms in the promoter regions
      of IL-6, IL-10 and NF-kappaB1 genes were assessed in 167 patients with DLBCL and
      99 controls and correlated with interleukin-6 (IL-6) and IL-10 plasma levels.
      Outcome was analyzed in 137 patients treated with rituximab-based chemotherapy.
      The NF-kappaB1 - 94ATTG deletion was associated with increased IL-6 and IL-10 in
      DLBCL. High IL-6 concentration correlated with unfavorable prognostic factors
      included in the international prognostic index (IPI) and predicted for inferior
      progression-free (p = 0.007) and overall survival (p = 0.02). IL-6 levels
      remained a significant outcome predictor also including IPI as a covariate (p =
      0.006 for progression-free survival). Our data suggest that the NF-kappaB1
      genetic background influences IL-6 production in DLBCL, and that high IL-6
      concentration is an independent prognostic factor also in the "rituximab era."

PMID- 21902580
TI  - Expression of interleukin-15 and interleukin-15Ralpha in monocytes of HIV type 1
      infected patients with different courses of disease progression.
AB  - Interleukin-15 (IL-15) enhances the effector mechanisms of anti-HIV immune
      responses and thus is considered a potential adjuvant of HIV-1 vaccine. However,
      there are a lack of data concerning the relationships between IL-15 expression
      and regulation in HIV-1-infected patients and the course of disease progression.
      We found that IL-15, but not IL-15Ralpha, is expressed at significantly higher
      levels in the CD14(+) monocytes [stimulated or not with interferon (IFN)-gamma]
      of long-term nonprogressors (LTNP) than in those of HIV-1 progressors or healthy
      controls. There was no between-group difference in the amounts of soluble IL-15
      released from the cells. We also found that like the healthy controls, the LTNP
      expressed the IL-15 and IL-15Ralpha genes in a more coordinated manner than the
      progressors. Our findings show that there are significant differences in IL-15
      expression between patients with different courses of HIV infection, and that the
      coordinated expression of the IL-15 and IL-15Ralpha genes is dysregulated in
      patients with progressive disease. They also provide important information
      concerning the mechanisms of infection and the potential use of IL-15 as a
      therapeutic agent.

PMID- 21902582
TI  - Imbalanced production of cytokines by T cells associates with the
      activation/exhaustion status of memory T cells in chronic HIV type 1 infection.
AB  - Chronic HIV-1 infection is characterized by immune cell dysfunctions driven by
      chronic immune activation. Plasma HIV-1 viral load (VL) is closely correlated
      with disease progression and the level of immune activation. However, the
      mechanism by which the persistent presence of HIV-1 damages immune cells is still
      not fully understood. To evaluate how HIV-1 affects disruption of T cell-mediated
      immune responses during chronic HIV-1 infection we determined the functional
      profiles of T cells from subjects with chronic HIV-1 infection. We measured the
      capacity of peripheral blood mononuclear cells (PBMCs) to produce 25 specific
      cytokines in response to nonspecific T cell stimulation, and found that the
      capacity to produce Th-1-related cytokines (MIP-1alpha, MIP-1beta, RANTES, IFN
      gamma, and MIG), sIL-2R, and IL-17, but not Th-2-related cytokines, was inversely
      correlated with plasma VL. The capacities to produce these cytokines were
      interrelated; notably, IL-17 production had a strong direct correlation with
      production of MIP-1alpha, MIP-1beta, RANTES, and IFN-gamma. In both CD4(+) and
      CD8(+) T cells, dysfunctional production of cytokines was associated with T cell
      activation (CD38 expression) and exhaustion (PD-1 and/or CTLA-4 expression)
      status of memory subsets. Although the capacity to produce these cytokines was
      recovered soon after multiple log(10) reduction of plasma viral levels by
      antiretroviral therapy, memory CD8(+) T cells remained activated and exhausted
      after prolonged virus suppression. Our data suggest that HIV-1 levels directly
      affect the ability of memory T cells to produce specifically Th1- and Th17
      related cytokines during chronic HIV-1 infection.

PMID- 21902581
TI  - Opportunistic and other infections in HIV-infected children in Latin America
      compared to a similar cohort in the United States.
AB  - Opportunistic and other infections have declined since the introduction of highly
      active antiretroviral therapy (HAART) in developed countries but few studies have
      addressed the impact of HAART in HIV-infected children from developing countries.
      This study examines the prevalence and incidence of opportunistic and other
      infections in Latin America during the HAART era. Vertically HIV-infected
      children enrolled in a cohort study between 2002 and 2007 were followed for the
      occurrence of 29 targeted infections. Cross-sectional and longitudinal analyses
      were performed to calculate the prevalence of infections before enrollment and
      the incidence rates of opportunistic and other infections after enrollment.
      Comparisons were made with data from a U.S. cohort (PACTG 219C). Of the 731
      vertically HIV-infected children 568 (78%) had at least one opportunistic or
      other infection prior to enrollment. The most prevalent infections were bacterial
      pneumonia, oral candidiasis, varicella, tuberculosis, herpes zoster, and
      Pneumocystis jiroveci pneumonia. After enrollment, the overall incidence was 23.5
      per 100 person-years; the most common infections (per 100 person-years) were
      bacterial pneumonia (7.8), varicella (3.0), dermatophyte infections (2.9), herpes
      simplex (2.5), and herpes zoster (1.8). All of these incidence rates were higher
      than those reported in PACTG 219C. The types and relative distribution of
      infections among HIV-infected children in Latin America in this study are similar
      to those seen in the United States but the incidence rates are higher. Further
      research is necessary to determine the reasons for these higher rates.

PMID- 21902584
TI  - HLA-dependent hypersensitivity reaction to nevirapine in Chinese Han HIV-infected
      patients.
AB  - In this study, one hundred and three HIV-positive Chinese Han patients treated
      with a nevirapine (NVP)-based regimens were investigated for the association
      between nevirapine hypersensitivity reaction (NVP HSR) and human leukocyte
      antigen (HLA) allele. HLA-Cw, -DRB1 alleles were determined in 32 NVP HSR cases
      and 71 NVP-tolerant patients. We found that considerable overlap was observed for
      the clinical and demographic characteristics of the 32 hypersensitive patients
      and 71 tolerant patients. Twelve out of 32 NVP HSR cases developed allergic
      hepatotoxicity. More HLA-Cw*04 alleles were observed in NVP HSR cases than in NVP
      tolerant cases (p=0.029). The frequency of HLA-DRB1*15 in NVP-tolerant cases was
      significant higher than that in NVP HSR cases ( p=0.018). Multivariate logistic
      regression identified that HLA-Cw*04 presence was a risk factor related to NVP
      HSR (p=0.030, OR=3.611, 95% CI of OR: 1.135-11.489). To clearly understanding its
      value in clinical practice, further studies involving larger cohorts of patients
      from different races with different levels of immune suppression are needed.

PMID- 21902583
TI  - C868T single nucleotide polymorphism and HIV type 1 disease progression among
      postpartum women in Kenya.
AB  - The C868T single nucleotide polymorphism in the CD4 receptor encodes an amino
      acid substitution of tryptophan for arginine in the third domain. Previous
      studies suggest that C868T increases the risk of HIV-1 acquisition; however, the
      influence of this single nucleotide polymorphism (SNP) on disease progression has
      not been established. The presence of the C868T polymorphism was not
      statistically significantly associated with HIV-1 disease progression outcomes in
      a cohort of postpartum Kenyan women.

PMID- 21902585
TI  - Epidemiology of HIV-related neuropathy: a systematic literature review.
AB  - We sought to identify and summarize the incidence and prevalence of neuropathy
      among HIV patients and subgroups. A systematic search of the literature was
      performed using MEDLINE and EMBASE. The relevant literature was identified based
      on predefined criteria. Prevalence data were collected from cross-sectional and
      cohort studies. Incidence data were collected from cohort and case-control
      studies. Thirty-seven studies were included of which there were 23 cohort
      studies, 13 cross-sectional studies, and one case-control study. The prevalence
      of neuropathy among HIV patients derived from 25 studies varied from 1.2% to
      69.4%. Regarding the development of neuropathy among HIV-positive patients,
      standardized by study duration, the rates per 100 person-years ranged from 0.7 to
      39.7. Among older patients there is a greater risk of neuropathy. The same seems
      to be the case for patients with more severe disease. Currently available studies
      providing information on the incidence and prevalence of neuropathy among HIV
      patients suggest a significant burden, but there is a great variation in results
      across studies. There is no definitive explanation for the variation. However, it
      underscores the fact that complexity of the disease, along with absence of
      standardized diagnostic criteria, has considerably influenced the methodologies
      and outcomes of the studies.

PMID- 21902586
TI  - Susceptibility of HIV type 2 primary isolates to CCR5 and CXCR4 monoclonal
      antibodies, ligands, and small molecule inhibitors.
AB  - Human immunodeficiency virus (HIV) entry into susceptible cells involves the
      interaction between viral envelope glycoproteins with CD4 and a chemokine
      receptor (coreceptor), namely CCR5 and CXCR4. This interaction has been studied
      to enable the discovery of a new class of antiretroviral drugs that targets the
      envelope glycoprotein-coreceptor interaction. However, very few data exist
      regarding HIV-2 susceptibility to these coreceptor inhibitors. With this work we
      aimed to identify this susceptibility in order to assess the potential use of
      these molecules to treat HIV-2-infected patients and to further understand the
      molecular basis of HIV-2 envelope glycoprotein interactions with CCR5 and CXCR4.
      We found that CCR5-using HIV-2 isolates are readily inhibited by maraviroc, TAK
      779, and PF-227153, while monoclonal antibody 2D7 shows only residual or no
      inhibitory effects. The anti-HIV-2 activity of CXCR4-targeted molecules reveals
      that SDF-1alpha/CXCL12 inhibited all HIV-2 tested except one, while mAb 12G5
      inhibited the replication of only two isolates, showing residual inhibitory
      effects with all the other CXCR4-using viruses. A major conclusion from our
      results is that infection by HIV-2 primary isolates is readily blocked in vitro
      by maraviroc, at concentrations similar to those required for HIV-1. The
      susceptibility to maraviroc was independent of CD4(+) T cell counts or clinical
      stage of the patient from which the virus was obtained. These findings indicate
      that maraviroc could constitute a reliable therapeutic alternative for HIV-2
      infected patients, as long as they are infected with CCR5-using variants, and
      this may have direct implications for the clinical management of HIV-2-infected
      patients.

PMID- 21902587
TI  - HIV type 1 genetic variation in foreskin and blood from subjects in Rakai,
      Uganda.
AB  - The foreskin contains a subset of dendritic cells, macrophages, and CD4(+) and
      CD8(+) T cells that may be targets for initial HIV infection in female-to-male
      sexual transmission of HIV-1. We present analyses comparing HIV-1 sequences
      isolated from foreskin DNA and serum RNA in 12 heterosexual men enrolled in an
      adult male circumcision trial performed in Rakai, Uganda. Phylogenetic analysis
      demonstrated three topologies: (1) little divergence between foreskin and serum,
      (2) multiple genetic bottlenecks occurring in both foreskin and serum, and (3)
      complete separation of foreskin and serum populations. The latter tree topology
      provided evidence that foreskin may serve as a reservoir for distinct HIV-1
      strains. Distance and recombination analysis also demonstrated that viral
      genotypes in the foreskin might segregate independently from the circulating pool
      of viruses.

PMID- 21902588
TI  - Identification of new CRF51_01B in Singapore using full genome analysis of three
      HIV type 1 isolates.
AB  - A recent HIV-1 molecular epidemiology survey in Singapore identified a novel
      CRF01_AE/B recombinant form, which accounted for 13 (11.9%) of 109 patient
      samples. Peripheral blood mononuclear cell DNA from three of these 13 patients
      was used to generate near full-length sequences to characterize the novel
      CRF01_AE/B recombinant form. The three isolates had a recombinant structure
      composed of CRF01_AE and subtype B, and shared identical breakpoints. As the
      three patients were not epidemiologically linked, this recombinant form has been
      designated CRF51_01B. Identification of the novel recombinant forms indicates
      ongoing active HIV-1 transmission in Singapore.

PMID- 21902589
TI  - Near full-length sequence analysis of two new HIV type 1 unique (CRF01_AE/B)
      recombinant forms among men who have sex with men in China.
AB  - Recombination contributes substantially to the genetic diversity of HIV-1, and is
      likely to occur in populations in which multiple subtypes circulate. Molecular
      epidemiological studies showed that subtype B, CRF01_AE, and CRF07_BC are
      currently circulating in parallel among men who have sex with men (MSM) in China,
      suggesting the possible emergence of new recombinants. In the present study, we
      identified two new HIV Type 1 unique (CRF01_AE /B) recombinant forms in this
      population by near full-length genomic analysis. Our data provided the first
      description of the near full-length genomes of these new CRF01_AE/B recombinants
      as well as important insights into the complexity of HIV-1 recombinant strains
      currently in circulation among MSM in China. These data highlight the importance
      of continuous surveillance of the dynamic change of HIV-1 subtypes and new
      recombinants among the MSM population.

PMID- 21902591
TI  - Nonrandom distribution of cryptic repeating triplets of purines and pyrimidines
      (RNY)(n) in gp120 of HIV Type1.
AB  - We have analyzed purine (R) and pyrimidine (Y) codon patterns in variable and
      constant regions of HIV-1 gp120 in seven patients infected with different HIV-1
      subtypes and naive to antiretroviral therapy. We have calculated the relative
      frequency of each in-frame codon RNY, YNR, RNR, and YNY (N=any nucleotide) in
      variable and constant regions of gp120, in the sequence within indels and at
      indels' flanking sites. Our data show that hypervariable regions V1, V2, V4, and
      V5 are characterized by the presence of long stretches of RNY codons constituting
      the majority of the sequence portion within insertions/deletions. In full-length
      gp120 and within inserted/deleted fragments the number of AVT (V=A, C, G) codons
      did not exceed 50% of the total RNY codons. RNY strings in variable regions
      spanned up to 21 codons and were always in frame. In contrast, RNY strings in
      constant regions were mostly out of frame and their length was limited to five
      codons. The frequency of the codon RNY was found to be significantly higher in
      variable regions (p<0.0001; t-test), within indels, and at indels' flanking sites
      (p<0.0001; chi(2) test). Analysis of the distribution of RNY strings equal to or
      longer than five codons in the full genome of HXB2 also shows that these
      sequences are mostly out of frame, unless they contain a potential N
      glycosylation site or an asparagine. These data suggest that cryptic repeats of
      RNY may play a role in the genesis of multiple base insertions and deletions in
      hypervariable regions of gp120.

PMID- 21902590
TI  - Diversity of HIV type 1 envelope (V3-V5) sequence in HIV type 1-infected Indian
      children.
AB  - Abstract   We assessed the viral envelope (V3-V5 region) sequence diversity from
      13 HIV-1-infected Indian children from north India. All of the 13 children were
      found to be infected with subtype C viruses. One of the viral sequences exhibited
      usage of the CXCR4 coreceptor predicted by Web PSSM and Geno2pheno tools. This
      virus also had a longer V3 sequence with 37 amino acids, a GRGQ motif, and a
      methionine residue before it (AIIMS_307). A unique finding was the complete
      deletion of the V4 region of another virus (AIIMS_363). High sequence diversity
      was observed in the envelope of the HIV-1-infected Indian children.

PMID- 21902592
TI  - Genetic diversity and drug resistance profiles in HIV type 1- and HIV type 2
      infected patients from Cape Verde Islands.
AB  - Our aim was to characterize for the first time the genetic diversity of HIV in
      Cape Verde Islands as well as the drug resistance profiles in treated and
      untreated patients. Blood specimens were collected from 41 HIV-1 and 14 HIV-2
      patients living in Santiago Island. Half of the patients were on antiretroviral
      treatment (ART). Pol and env gene sequences were obtained using in-house methods.
      Phylogenetic analysis was used for viral subtyping and the Stanford Algorithm was
      used for resistance genotyping. For HIV-1, the amplification of pol and env was
      possible in 27 patients (66%). HIV-1 patients were infected with subtypes G (13,
      48%), B (2, 7%), F1 (2, 7%), and CRF02_AG (2, 7%), and complex recombinant forms
      including a new C/G variant (n=8, 30%). Drug resistance mutations were detected
      in the PR and RT of three (10%) treated patients. M41L and K103N transmitted drug
      resistance mutations were found in 2 of 17 (12%) untreated patients. All 14 HIV-2
      isolates belonged to group A. The origin of 12 strains was impossible to
      determine whereas two strains were closely related to the historic ROD strain. In
      conclusion, in Cape Verde there is a long-standing HIV-2 epidemic rooted in ROD
      like strains and a more recent epidemic of unknown origin. The HIV-1 epidemic is
      caused by multiple subtypes and complex recombinant forms. Drug resistance HIV-1
      strains are present at moderate levels in both treated and untreated patients.
      Close surveillance in these two populations is crucial to prevent further
      transmission of drug-resistant strains.

PMID- 21902593
TI  - Evaluating immune correlates in HIV type 1 vaccine efficacy trials: what RV144
      may provide.
AB  - Since the RV144 vaccine combination showed efficacy in a Phase III trial, it
      provides an opportunity to generate hypotheses about the immune responses
      necessary for protection against HIV-1 infection, and these results could help
      devise vaccine candidates with higher efficacy. Here we describe how researchers
      can determine the correlates of immune protection for an HIV/AIDS vaccine,
      particularly in the context of the RV144 trial, and we discuss the terminology
      used to describe correlates and surrogates.

PMID- 21902594
TI  - The MHC Class I heavy chain structurally conserved cysteines 101 and 164
      participate in HLA-B27 dimer formation.
AB  - AIMS: The human leukocyte antigen (HLA)-B27 is strongly associated with a group
      of inflammatory arthritic disorders known as the spondyloarthropathies (SpAs).
      The unusual biochemistry of HLA-B27 has been proposed to participate in disease
      development, especially the enhanced ability of HLA-B27 to form several heavy
      chain-dimer populations. HLA-B27 possesses three unpaired cysteine (C) residues
      at position 67, 308, and 325, in addition to the four conserved cysteine residues
      at p101, 164, 203, and 259. C67 was proposed to participate in dimer formation of
      recombinant HLA-B27 protein and in vivo heavy chain-dimers. However, the
      structurally conserved C164 was demonstrated to participate in endoplasmic
      reticulum (ER) resident heavy chain-dimer formation. We therefore wanted to
      determine whether these aggregates involve cysteines other than C164 and the
      basis for the difference between the observed heavy chain-dimer species. RESULTS:
      We determined that C164 and C101 can form distinct dimer structures and that the
      heterogenous nature of heavy chain-dimer species is due to differences in both
      redox status and conformation. Different HLA-B27 dimer populations can be found
      in physiologically relevant cell types derived from HLA-B27-positive patients
      with inflammatory arthritis. In addition, HLA-B27 dimer formation can be
      correlated with cellular stress induction. INNOVATION: The use of both
      mutagenesis and manipulating cellular redox environments demonstrates that HLA
      B27 dimerization requires both specific cysteine?cysteine interactions and
      conformations with differing redox states. CONCLUSION: HLA-B27 heavy chain
      dimerization is a complex process and these findings provide an insight into HLA
      B27 misfolding and a potential contribution to inflammatory disease development.

PMID- 21902595
TI  - Crucial role of nuclear Ago2 for hUCB-MSCs differentiation and self-renewal via
      stemness control.
AB  - AIMS: Argonaute2 (Ago2) has intrinsic endonuclease activity in microRNA
      processing that plays a fundamental role in gene regulation. In this study, we
      demonstrate novel functions and molecular mechanisms of nuclear Ago2 in the self
      renewal and plasticity of human umbilical cord blood-derived mesenchymal stem
      cells (hUCB-MSCs). RESULTS: Nuclear Ago2 binds to a set of regulatory genes,
      including Ago2 itself, Oct4, Sox2, Nanog, GATA, STAT3, and beta-catenin, that
      potentially target fundamental functions of stem cells. Direct regulation of the
      stemness genes by nuclear Ago2 was also crucial for cell self-renewal, survival,
      and differentiation into various types of tissues or cells, including neural
      cells and beta-cells. Moreover, regulation of Oct4 by Ago2 directly controls the
      stem cell plasticity-determining signal mediators JAK2/STAT3 and Wnt5A/beta
      catenin and positively regulates cell proliferation and differentiation via
      blockage of ROS generation and P38/JNK inactivation. Nuclear Ago2 or stemness
      expression lead increased stem cell identity and decreased differentiation into a
      mesodermal lineage but also led to increased neural differentiation and beta-cell
      differentiation in hUCB-MSCs. Nuclear Ago2-mediated stemness expression in hUCB
      MSCs is also involved in cell survival, helping cells escape apoptotic cell death
      via inactivation of P38/JNK, caspase-3, and Bax. INNOVATION AND CONCLUSION: This
      study reveals that nuclear Ago2 globally controls stem cell self-renewal and
      differentiation through direct regulation of stemness genes and important signal
      mediator activation following inactivation of ROS/P38/JNK and activation of the
      JAK/STAT3 and Wnt/ beta-catenin signal pathways.

PMID- 21902596
TI  - Oxidative stress in chronic pancreatitis: pathophysiological relevance and
      management.
AB  - SIGNIFICANCE: Chronic pancreatitis (CP) is a progressive, inflammatory disease of
      the pancreas leading to slow destruction of pancreatic parenchyma and progressive
      fibrosis. The pathophysiological mechanism of CP is not well understood. RECENT
      ADVANCES: A pathophysiologic role of oxidative stress in CP has, however, been
      suggested in recent years. Pancreatic acinar cells contain phase I cytochrome
      P450 (CYP 450) biotransforming enzymes and phase II conjugation reactions for the
      metabolism of xenobiotics. The oxidative stress in the acinar cell may result
      from generation of free radicals through CYP induction, concurrent exposure to a
      chemical that undergoes bioactivation, and insufficiency of micronutrients that
      are required to sustain antioxidant (AO) capacity. CRITICAL ISSUES: Studies have
      shown that there is indeed a state of oxidative stress as evidenced by increased
      levels of products of oxidative stress and reduced AO capacity in patients with
      CP. A recent randomized, controlled trial has shown beneficial effect of AO
      therapy in CP; a combination of AOs (0.54 g ascorbic acid, 9000 IU beta-carotene,
      270 IU alpha-tocopherol, 600 MUg organic selenium, and 2 g methionine per day in
      divided doses) led to significant reductions in pain and oxidative stress in
      patients with CP. FUTURE DIRECTIONS: Similar studies from other centers and
      multicenter studies should confirm that oxidative stress plays an important role
      in the pathophysiology of CP and supplementation with AOs leads to significant
      pain relief in patients with this disease.

PMID- 21902598
TI  - Cognitive function in prepubertal children with obstructive sleep apnea: a
      modifying role for NADPH oxidase p22 subunit gene polymorphisms?
AB  - Pediatric obstructive sleep apnea (OSA) may lead to neurocognitive dysfunction,
      but not in everyone affected. The frequencies of NADPH oxidase (NOX)
      polymorphisms in the p22phox subunit were similar between children with OSA and
      controls, except for rs6520785 and rs4673, the latter being significantly more
      frequent among the OSA children without deficits than with deficits (p<0.02).
      Similarly, 8-hydroxydeoxyguanine urine levels and NOX activity were lower among
      children without cognitive deficits and particularly among those with the rs4673
      polymorphism. Thus, polymorphisms within the NOX gene or its functional subunits
      may account for important components of the variance in cognitive function
      deficits associated with OSA in children.

PMID- 21902600
TI  - Factors related to pulse wave velocity and augmentation index in chronic
      hemodialysis patients.
AB  - BACKGROUND: Augmentation index (AIx) and pulse wave velocity (PWV) are early
      markers of atherosclerotic vascular changes and also have been shown to be
      predictive of cardiovascular disease and total mortality. The aim of our study
      was to evaluate the relationship between PWV and AIx-HR75, which is the corrected
      form of AIx according to a heart rate of 75 beats/min, echocardiographic
      parameters and biochemical parameters in chronic hemodialysis (HD) patients.
      SUBJECTS AND METHODS: AIx-HR75 and PWV were measured in 556 HD patients by
      applanation tonometry using the SphygmoCor device. RESULTS: The mean PWV and AIx
      HR75 values of the study group were 10.2 +/- 2.4 and 28.4 +/- 10.2 m/s. A
      positive correlation was found between PWV and AIx-HR75 (r = 0.214, p = 0.000).
      AIx-HR75 correlated with age (r = 0.093, p = 0.028), body surface area (BSA) (r =
      -0.194, p = 0.000), mean arterial pressure (MAP) (r = 0.335, p = 0.000), pulse
      pressure (PP) (r = 0.212, p = 0.000), cardiothoracic index (r = 0.155, p =
      0.016), and presence of left ventricular hypertrophy (r = 0.152, p = 0.001). PWV
      correlated with MAP (r = 0.208, p = 0.000), PP (r = 0.098, r = 0.021), left
      ventricular mass (r = 0.105, p = 0.023), and predialysis sodium level (r = 
      0.105, p = 0.023). In the multivariate analyses, PWV was associated with MAP (t =
      3.78, p = 0.000), presence of diabetes (t = 3.20, p = 0.001), and predialysis
      sodium level (t = -2.06, p = 0.040), and AIx-HR75 was associated with age (t =
      2.48, p = 0.014), female sex (t = 3.98, p = 0.000), BSA (t = -2.15, p = 0.033),
      and MAP (t = 7.02, p = 0.000). CONCLUSION: There is a strong association between
      MAP and arterial stiffness parameters in HD patients. We feel that efficient
      control of blood pressure could lead to reduced arterial stiffness in HD
      patients.

PMID- 21902601
TI  - Low oxygen concentrations impair tissue development in tissue-engineered
      cardiovascular constructs.
AB  - Cardiovascular tissue engineering has shown considerable progress, but in vitro
      tissue conditioning to stimulate the development of a functional extracellular
      matrix still needs improvement. We investigated the environmental factor oxygen
      concentration for its potential to increase the amount of collagen and collagen
      cross-links, and therefore improve tissue quality. Cardiovascular tissue
      engineered (TE) constructs, made of rapidly degrading PGA/P4HB scaffold seeded
      with human vascular-derived cells, were cultured at 7%, 4%, 2%, 0.5% O(2) for 4
      weeks and compared to control cultures at 21% O(2). Tissue properties were
      evaluated by measuring the extracellular matrix production and mechanical
      behavior. The culture environment was monitored closely and the oxygen gradient
      throughout the constructs was simulated with a theoretical model. TE constructs
      cultured at 21%, 7% and 4% O(2) showed dense and homogeneous tissue formation
      with comparable strength, stiffness, collagen and collagen cross-link content. At
      2% O(2), collagen content and stiffness decreased, whereas at 0.5% O(2), hardly
      any tissue was formed. Overall, tissue properties deteriorated at the lowest
      oxygen concentrations, opposing our hypothesis that was based on previous culture
      at low oxygen concentrations. Further research will focus on establishing the
      balance between applied oxygen conditions (concentration and exposure time) and
      optimal tissue outcome.

PMID- 21902599
TI  - Mitochondrially targeted alpha-tocopheryl succinate is antiangiogenic: potential
      benefit against tumor angiogenesis but caution against wound healing.
AB  - AIMS: A plausible strategy to reduce tumor progress is the inhibition of
      angiogenesis. Therefore, agents that efficiently suppress angiogenesis can be
      used for tumor suppression. We tested the antiangiogenic potential of a
      mitochondrially targeted analog of alpha-tocopheryl succinate (MitoVES), a
      compound with high propensity to induce apoptosis. RESULTS: MitoVES was found to
      efficiently kill proliferating endothelial cells (ECs) but not contact-arrested
      ECs or ECs deficient in mitochondrial DNA, and suppressed angiogenesis in vitro
      by inducing accumulation of reactive oxygen species and induction of apoptosis in
      proliferating/angiogenic ECs. Resistance of arrested ECs was ascribed, at least
      in part, to the lower mitochondrial inner transmembrane potential compared with
      the proliferating ECs, thus resulting in the lower level of mitochondrial uptake
      of MitoVES. Shorter-chain homologs of MitoVES were less efficient in angiogenesis
      inhibition, thus suggesting a molecular mechanism of its activity. Finally,
      MitoVES was found to suppress HER2-positive breast carcinomas in a transgenic
      mouse as well as inhibit tumor angiogenesis. The antiangiogenic efficacy of
      MitoVES was corroborated by its inhibitory activity on wound healing in vivo.
      INNOVATION AND CONCLUSION: We conclude that MitoVES, a mitochondrially targeted
      analog of alpha-tocopheryl succinate, is an efficient antiangiogenic agent of
      potential clinical relevance, exerting considerably higher activity than its
      untargeted counterpart. MitoVES may be helpful against cancer but may compromise
      wound healing.

PMID- 21902597
TI  - Mitochondria and cell bioenergetics: increasingly recognized components and a
      possible etiologic cause of Alzheimer's disease.
AB  - SIGNIFICANCE: Mitochondria and brain bioenergetics are increasingly thought to
      play an important role in Alzheimer's disease (AD). RECENT ADVANCES: Data that
      support this view are discussed from the perspective of the amyloid cascade
      hypothesis, which assumes beta-amyloid perturbs mitochondrial function, and from
      an opposite perspective that assumes mitochondrial dysfunction promotes brain
      amyloidosis. A detailed review of cytoplasmic hybrid (cybrid) studies, which
      argue mitochondrial DNA (mtDNA) contributes to sporadic AD, is provided. Recent
      AD endophenotype data that further suggest an mtDNA contribution are also
      summarized. CRITICAL ISSUES AND FUTURE DIRECTIONS: Biochemical, molecular,
      cybrid, biomarker, and clinical data pertinent to the mitochondria-bioenergetics
      AD nexus are synthesized and the mitochondrial cascade hypothesis, which
      represents a mitochondria-centric attempt to conceptualize sporadic AD, is
      discussed.

PMID- 21902602
TI  - Human adipose tissue extract induces angiogenesis and adipogenesis in vitro.
AB  - The induction of adequate vascularization, a major challenge in tissue
      engineering, has been tried with numerous methods but with unsatisfactory
      results. Adipose tissue, an active endocrine organ with dense vasculature,
      secretes a wide number of angiogenic and adipogenic factors and seems an
      attractive source for these bioactive factors. We produced a novel cell-free
      extract from mature human adipose tissue (adipose tissue extract [ATE]) and
      analyzed the ability of this extract to induce angiogenesis and adipogenesis in
      vitro and studied the cytokine and growth factor composition of ATE with ELISA
      and cytokine array. We demonstrate that ATE, when added as cell culture
      supplement, effectively induced triglyceride accumulation in human adipose stem
      cells at concentrations from 200 MUg/mL upward in less than a week and caused
      elevated levels of adipocyte differentiation markers (proliferator-activated
      receptor gamma and acyl-CoA-binding protein) when treated with at least 350
      MUg/mL of ATE. ATE induced angiogenesis from 450 MUg/mL upward after a week in
      vitro. ATE contained numerous angiogenic and adipogenic factors, for example,
      vascular endothelial growth factor, basic fibroblast growth factor, interleukin
      6, adiponectin, angiogenin, leptin, and insulin-like growth factor-I, as well as
      lower levels of a wide variety of other cytokines. We here present a novel cell
      free angiogenesis- and adipogenesis-inducing agent that is cell-free and easy to
      produce, and its effect is dose dependent and its composition can be easily
      modified. Therefore, ATE is a promising novel agent to be used for angiogenesis
      induction to overcome the challenge of vascularization and for adipogenesis
      induction in a wide variety of tissue engineering applications in vitro and in
      vivo. ATE is also efficient for reproduction and modeling of natural adipogenesis
      in vitro for, for example, obesity and diabetes studies.

PMID- 21902603
TI  - Renal tissue engineering with decellularized rhesus monkey kidneys: age-related
      differences.
AB  - New therapies for severely damaged kidneys are needed due to limited regenerative
      capacity and organ donor shortages. The goal of this study was to repopulate
      decellularized kidney sections in vitro and to determine the impact of donor age
      on recellularization. This was addressed by generating decellularized kidney
      scaffolds from fetal, juvenile, and adult rhesus monkey kidney sections using a
      procedure that removes cellular components while preserving the structural and
      functional properties of the native extracellular matrix (ECM). Kidney scaffolds
      were recellularized using explants from different age groups (fetal, juvenile,
      adult) and fetal renal cell fractions. Results showed vimentin+ cytokeratin+
      calbindin+ cell infiltration and organization around the scaffold ECM. The extent
      of cellular repopulation was greatest with scaffolds from the youngest donors,
      and with seeding of mixed fetal renal aggregates that formed tubular structures
      within the kidney scaffolds. These findings suggest that decellularized kidney
      sections from different age groups can be effectively repopulated with donor
      cells and the age of the donor is a critical factor in repopulation efficiency.

PMID- 21902604
TI  - Isolation of cardiovascular precursor cells from the human fetal heart.
AB  - Weakening of cardiac function in patients with heart failure results from a loss
      of cardiomyocytes in the damaged heart. Cell replacement therapies as a way to
      induce myocardial regeneration in humans could represent attractive alternatives
      to classical drug-based approaches. However, a suitable source of precursor
      cells, which could produce a functional myocardium after transplantation, remains
      to be identified. In the present study, we isolated cardiovascular precursor
      cells from ventricles of human fetal hearts at 12 weeks of gestation. These cells
      expressed Nkx2.5 but not late cardiac markers such as alpha-actinin and troponin
      I. In addition, proliferating cells expressed the mesenchymal stem cell markers
      CD73, CD90, and CD105. Evidence for functional cardiogenic differentiation in
      vitro was demonstrated by the upregulation of cardiac gene expression as well as
      the appearance of cells with organized sarcomeric structures. Importantly,
      differentiated cells presented spontaneous and triggered calcium signals.
      Differentiation into smooth muscle cells was also detected. In contrast,
      precursor cells did not produce endothelial cells. The engraftment and
      differentiation capacity of green fluorescent protein (GFP)-labeled cardiac
      precursor cells were then tested in vivo after transfer into the heart of
      immunodeficient severe combined immunodeficient mice. Engrafted human cells were
      readily detected in the mouse myocardium. These cells retained their cardiac
      commitment and differentiated into alpha-actinin-positive cardiomyocytes.
      Expression of connexin-43 at the interface between GFP-labeled and endogenous
      cardiomyocytes indicated that precursor-derived cells connected to the mouse
      myocardium. Together, these results suggest that human ventricular nonmyocyte
      cells isolated from fetal hearts represent a suitable source of precursors for
      cell replacement therapies.

PMID- 21902606
TI  - Differentiation of human Wharton's jelly cells toward nucleus pulposus-like cells
      after coculture with nucleus pulposus cells in vitro.
AB  - The aim of this study was to evaluate whether human Wharton's jelly cells (WJCs)
      could be differentiated into nucleus pulposus (NP)-like cells by coculturing with
      NP cells (NPCs) in vitro. WJCs were isolated from the human umbilical cord, and
      NPCs were isolated from healthy human intervertebral disc. After coculturing WJCs
      with NPCs in a monolayer environment with or without cell-cell contact for 7
      days, the real-time polymerase chain reaction showed the relative gene
      expressions of NP-marker genes (aggrecan, type II collagens, and SRY-type HMG box
      9) were significantly increased (p<0.05) in all groups, and the increase in the
      group of 25:75/WJCs:NPCs was the largest (p<0.05). The increases of relative gene
      expression in WJCs cocultured with cell-cell contact were larger than those
      cocultured without contact in all ratios (p<0.05). WJCs were positive for
      telomerase expression. Flow cytometry analyses showed that WJCs expressed CD73,
      CD105, CD90, CD29, CD166, and human leukocyte antigen (HLA)-ABC while being
      negative for the expression of CD34, CD45, and HLA-DR. The results of this study
      indicated that the WJCs had the feature of the mesenchymal stem cell and might be
      induced to differentiate to NP-like cells by coculturing with NPCs.

PMID- 21902605
TI  - NELL-1 promotes cartilage regeneration in an in vivo rabbit model.
AB  - Repair of cartilage due to joint trauma remains challenging due to the poor
      healing capacity of cartilage and adverse effects related to current growth
      factor-based strategies. NELL-1 (Nel-like molecule-1; Nel [a protein strongly
      expressed in neural tissue encoding epidermal growth factor like domain]), a
      protein first characterized in the context of premature cranial suture fusion, is
      believed to accelerate differentiation along the osteochondral lineage. We
      previously demonstrated the ability of NELL-1 protein to maintain the
      cartilaginous phenotype of explanted rabbit chondrocytes in vitro. Our objective
      in the current study is to determine whether NELL-1 can affect endogenous
      chondrocytes in an in vivo cartilage defect model. To generate the implant, NELL
      1 was incorporated into chitosan nanoparticles and embedded into alginate
      hydrogels. These implants were press fit into 3-mm circular osteochondral defects
      created in the femoral condylar cartilage of 3-month-old New Zealand White
      rabbits (n=10). Controls included unfilled defects (n=8) and defects filled with
      phosphate-buffered saline-loaded chitosan nanoparticles embedded in alginate
      hydrogels (n=8). Rabbits were sacrificed 3 months postimplantation for
      histological analysis. Defects filled with alginate containing NELL-1
      demonstrated significantly improved cartilage regeneration. Remarkably, histology
      of NELL-1-treated defects closely resembled that of native cartilage, including
      stronger Alcian blue and Safranin-O staining and increased deposition of type II
      collagen and absence of the bone markers type I collagen and Runt-related
      transcription factor 2 (Runx2) as demonstrated by immunohistochemistry. Our
      results suggest that NELL-1 may produce functional cartilage with properties
      similar to native cartilage, and is an exciting candidate for tissue engineering
      based approaches for treating diverse pathologies of cartilage defects and
      degeneration.

PMID- 21902607
TI  - Injectable biodegradable polycaprolactone-sebacic acid gels for bone tissue
      engineering.
AB  - Tissue engineering constitutes a promising alternative technology to
      transplantation medicine by creating viable substitutes for failing tissues or
      organs. The ability to manipulate and reconstitute tissue function has tremendous
      clinical implications and will most likely play a key role in cell and gene
      therapies in the coming years. In the present work, a novel injectable and
      biodegradable biomaterial is reported that could be injected on the human body
      with a surgical syringe. The material prepared is a blend of polycaprolactone
      (PCL), a biodegradable and elastic biomedical polymer, and sebacic acid, a
      natural polymer part of castor oil with low molecular weight to accelerate the
      slow degradation rate of PCL. The biocompatibility of the blend was evaluated in
      vitro and its in vivo behavior was also assessed through subcutaneous and bone
      implantation in rats to evaluate its tissue-forming ability and degradation rate.
      The results allowed the conclusion that the gel is biocompatible, promotes the
      differentiation of mesenchymal stem cells, and presents an adequate degradation
      rate for use in bone tissue engineering. In vivo the gel blends promoted tissue
      regeneration and adverse reactions were not observed on subcutaneous and bone
      implants.

PMID- 21902608
TI  - Three-dimensional engineered bone-ligament-bone constructs for anterior cruciate
      ligament replacement.
AB  - The anterior cruciate ligament (ACL), a major stabilizer of the knee, is commonly
      injured. Because of its intrinsic poor healing ability, a torn ACL is usually
      reconstructed by a graft. We developed a multi-phasic, or bone-ligament-bone,
      tissue-engineered construct for ACL grafts using bone marrow stromal cells and
      sheep as a model system. After 6 months in vivo, the constructs increased in
      cross section and exhibited a well-organized microstructure, native bone
      integration, a functional enthesis, vascularization, innervation, increased
      collagen content, and structural alignment. The constructs increased in stiffness
      to 52% of the tangent modulus and 95% of the geometric stiffness of native ACL.
      The viscoelastic response of the explants was virtually indistinguishable from
      that of adult ACL. These results suggest that our constructs after implantation
      can obtain physiologically relevant structural and functional characteristics
      comparable to those of adult ACL. They present a viable option for ACL
      replacement.

PMID- 21902609
TI  - Evaluation of angiogenesis and osteogenesis.
AB  - Bone regeneration has long been a major focus for tissue engineers and the
      importance of vascularization to the bone regeneration process has been well
      documented. Over the past decade, technological advances in the areas of stem
      cell biology, scaffold fabrication, and protein engineering have significantly
      enhanced our understanding of the interplay between vascularization and bone
      growth. This review, therefore, describes the commonly used models for
      investigating the complex interactions between osteoblastic cells and endothelial
      cells, evaluates the different tools utilized to investigate the relationship
      between vascularization and bone growth in vivo, and finally, summarizes possible
      areas of research related to therapeutic development.

PMID- 21902610
TI  - The niche as a target for hematopoietic manipulation and regeneration.
AB  - Hematopoietic stem cells (HSCs), rare primitive cells capable of reconstituting
      all blood cell lineages, are the only stem cells currently routinely used for
      therapeutic purposes. Clinical experience has shown that HSC number is an
      important limiting factor in treatment success. Strategies to expand HSCs are of
      great clinical appeal, as they would improve therapeutic use of these cells in
      stem cell transplantation and in conditions of bone marrow failure. The
      microenvironment in which HSCs reside, known as the niche, has long been
      considered a critical regulator of HSCs. Data accumulated over the past decade
      strongly confirm the importance of the niche in HSC behavior. A number of niche
      components as well as signaling pathways, such as Notch, have been implicated in
      the interaction of the microenvironment with HSCs and continue to be genetically
      evaluated in the hope of defining the critical elements that are required and
      which, if modified, can initiate HSC behaviors. In this review, we highlight the
      known characteristics of HSCs, challenges in their expansion, the niche
      phenomenon, and explain why niche stimulated HSC expansion is of utmost interest
      in the field, while beginning to bring to the fore potential caveats of niche
      manipulation. Lastly, the potential pitfalls of avoiding malignancy and
      controlling self-renewal versus differentiation will be briefly reviewed.

PMID- 21902611
TI  - Improved mesenchymal stem cells attachment and in vitro cartilage tissue
      formation on chitosan-modified poly(L-lactide-co-epsilon-caprolactone) scaffold.
AB  - Considering the load-bearing physiological requirement of articular cartilage,
      scaffold for cartilage tissue engineering should exhibit appropriate mechanical
      responses as natural cartilage undergoing temporary deformation on loading with
      little structural collapse, and recovering to the original geometry on unloading.
      A porous elastomeric poly l-lactide-co-E-caprolactone (PLCL) was generated and
      crosslinked at the surface to chitosan to improve its wettability. Human bone
      marrow derived mesenchymal stem cells (MSC) attachment, morphological change,
      proliferation and in vitro cartilage tissue formation on the chitosan-modified
      PLCL scaffold were compared with the unmodified PLCL scaffold. Chitosan surface
      promoted more consistent and even distribution of the seeded MSC within the
      scaffold. MSC rapidly adopted a distinct spread-up morphology on attachment on
      the chitosan-modified PLCL scaffold with the formation of F-actin stress fiber
      which proceeded to cell aggregation; an event much delayed in the unmodified
      PLCL. Enhanced cartilage formation on the chitosan-modified PLCL was shown by
      real-time PCR analysis, histological and immunochemistry staining and biochemical
      assays of the cartilage extracellular matrix components. The Young's modulus of
      the derived cartilage tissues on the chitosan-modified PLCL scaffold was
      significantly increased and doubled that of the unmodified PLCL. Our results show
      that chitosan modification of the PLCL scaffold improved the cell compatibility
      of the PLCL scaffold without significant alteration of the physical elastomeric
      properties of PLCL and resulted in the formation of cartilage tissue of better
      quality.

PMID- 21902612
TI  - Cell sources for bone tissue engineering: insights from basic science.
AB  - One of the goals of bone tissue engineering is to design delivery methods for
      skeletal stem/progenitor cells to repair or replace bone. Although the materials
      used to retain cells play a central role in the quality of the constructs, the
      source of cells is key for bone regeneration. Bone marrow is the most common cell
      source, but other tissues are now being explored, such as the periosteum, fat,
      muscle, cord blood, and embryonic or induced pluripotent stem cells. The
      therapeutic effect of exogenous stem/progenitor cells is accepted, yet their
      contribution to bone repair is not well defined. The in vitro osteo- and/or
      chondrogenic potential of these skeletal progenitors do not necessarily predict
      their differentiation potential in vivo and their function may be affected by
      their ability to home correctly to bone. This review provides an overview of
      animal models used to test the efficacy of cell-based approaches. We examine the
      mechanisms of endogenous cell recruitment during bone repair and compare the role
      of local versus systemic cell recruitment. We discuss how the normal repair
      process can help define efficacious cell sources for bone tissue engineering and
      improve their methods of delivery.

PMID- 21902614
TI  - Bone tissue engineering and regeneration: from discovery to the clinic--an
      overview.
AB  - A National Institutes of Health sponsored workshop "Bone Tissue Engineering and
      Regeneration: From Discovery to the Clinic" gathered thought leaders from
      medicine, science, and industry to determine the state of art in the field and to
      define the barriers to translating new technologies to novel therapies to treat
      bone defects. Tissue engineering holds enormous promise to improve human health
      through prevention of disease and the restoration of healthy tissue functions.
      Bone tissue engineering, similar to that for other tissues and organs, requires
      integration of multiple disciplines such as cell biology, stem cells,
      developmental and molecular biology, biomechanics, biomaterials science, and
      immunology and transplantation science. Although each of the research areas has
      undergone enormous advances in last decade, the translation to clinical care and
      the development of tissue engineering composites to replace human tissues has
      been limited. Bone, similar to other tissue and organs, has complex structure and
      functions and requires exquisite interactions between cells, matrices,
      biomechanical forces, and gene and protein regulatory factors for sustained
      function. The process of engineering bone, thus, requires a comprehensive
      approach with broad expertise. Although in vitro and preclinical animal studies
      have been pursued with a large and diverse collection of scaffolds, cells, and
      biomolecules, the field of bone tissue engineering remains fragmented up to the
      point that a clear translational roadmap has yet to emerge. Translation is
      particularly important for unmet clinical needs such as large segmental defects
      and medically compromised conditions such as tumor removal and infection sites.
      Collectively, manuscripts in this volume provide luminary examples toward
      identification of barriers and strategies for translation of fundamental
      discoveries into clinical therapeutics.

PMID- 21902616
TI  - Harnessing the parathyroid hormone, Wnt, and bone morphogenetic protein signaling
      cascades for successful bone tissue engineering.
AB  - Tissue engineering holds great promise as a way of enhancing the normal
      regenerative potential of bone. By deconstructing the skeleton into its
      components and examining how each component influences the reparative response,
      it is clear that cells resident in bone, bioactive molecules produced by these
      cells and those brought into bone via the circulation and the unique
      extracellular matrix that makes up the bone itself are involved in a continuous
      and ever-changing set of reciprocal interactions during regeneration. Reviewed
      here is current information regarding the efficacy of 3 prominent signaling
      cascades that orchestrate bone formation, parathyroid hormone, Wnt and bone
      morphogenetic proteins, in enhancing bone repair. I suggest how we might
      successfully generate new bone in increasingly complex clinical situations by
      modulating the availability of these signals to cells already present within bone
      tissue.

PMID- 21902615
TI  - A novel method for the fabrication of fibrin-based electrospun nanofibrous
      scaffold for tissue-engineering applications.
AB  - In this study, fibrin, which is superior to fibrinogen in both structural and
      functional properties, has for the first time been electrospun successfully into
      uniform nano fibers resembling the extracellular matrix (ECM). The methods of
      fabrication and characterization of this unique scaffold are presented. Using
      poly (vinyl) alcohol as an "electrospinning-driving" polymer, we have developed a
      novel method for the fabrication of fibrin into a nanofibrous scaffold for
      various tissue-engineering applications starting from human-plasma-derived
      fibrinogen and thrombin and combining these ingredients within the syringe of an
      electrospinning setup under high voltage. In this fashion, fibrin nanofibrous
      scaffold is produced in a one-step approach without the need for subsequent cross
      linking by synthetic agents that compromise the biological properties of the
      scaffold. Characterization of the electrospun membrane was done by scanning
      electron microscopy (SEM), Fourier transform infrared spectroscopy, and fibrin
      specific phosphotungstic acid hematoxylin staining. SEM data revealed the
      formation of bead-free fibers with a dimension ranging from 50-500 nm, which
      exactly mimics the fiber diameter of native ECM. Cell attachment and
      proliferation studies revealed that the scaffold supports the attachment,
      spreading, and proliferation of human umbilical cord blood-derived mesenchymal
      stem cells.

PMID- 21902613
TI  - Scaffold translation: barriers between concept and clinic.
AB  - Translation of scaffold-based bone tissue engineering (BTE) therapies to clinical
      use remains, bluntly, a failure. This dearth of translated tissue engineering
      therapies (including scaffolds) remains despite 25 years of research, research
      funding totaling hundreds of millions of dollars, over 12,000 papers on BTE and
      over 2000 papers on BTE scaffolds alone in the past 10 years (PubMed search).
      Enabling scaffold translation requires first an understanding of the challenges,
      and second, addressing the complete range of these challenges. There are the
      obvious technical challenges of designing, manufacturing, and functionalizing
      scaffolds to fill the Form, Fixation, Function, and Formation needs of bone
      defect repair. However, these technical solutions should be targeted to specific
      clinical indications (e.g., mandibular defects, spine fusion, long bone defects,
      etc.). Further, technical solutions should also address business challenges,
      including the need to obtain regulatory approval, meet specific market needs, and
      obtain private investment to develop products, again for specific clinical
      indications. Finally, these business and technical challenges present a much
      different model than the typical research paradigm, presenting the field with
      philosophical challenges in terms of publishing and funding priorities that
      should be addressed as well. In this article, we review in detail the technical,
      business, and philosophical barriers of translating scaffolds from Concept to
      Clinic. We argue that envisioning and engineering scaffolds as modular systems
      with a sliding scale of complexity offers the best path to addressing these
      translational challenges.

PMID- 21902617
TI  - Unraveling barrier properties of three different in-house human skin equivalents.
AB  - Human skin equivalents (HSEs) are three-dimensional culture models that are used
      as a model for native human skin. In this study the barrier properties of two
      novel HSEs, the fibroblast-derived matrix model (FDM) and the Leiden epidermal
      model (LEM), were compared with the full-thickness collagen model (FTM) and human
      skin. Since the main skin barrier is located in the lipid regions of the upper
      layer of the skin, the stratum corneum (SC), we investigated the epidermal
      morphology, expression of differentiation markers, SC permeability, lipid
      composition, and lipid organization of all HSEs and native human skin. Our
      results demonstrate that the barrier function of the FDM and LEM improved
      compared with that of the FTM, but all HSEs are more permeable than human skin.
      Further, the FDM and LEM have a relatively lower free fatty acid content than the
      FTM and human skin. Several similarities between the FDM, LEM and FTM were
      observed: (1) the morphology and the expression of the investigated
      differentiation markers were similar to those observed in native human skin,
      except for the observed expression of keratin 16 and premature expression of
      involucrin that were detected in all HSEs, (2) the lipids in the SC of all HSEs
      were arranged in lipid lamellae, similar to human skin, but show an increase in
      the number of lipid lamellae in the intercellular regions and (3) the SC lipids
      of all HSEs show a less densely packed lateral lipid organization compared with
      human SC. These findings indicate that the HSEs mimic many aspects of native
      human skin, but differ in their barrier properties.

PMID- 21902618
TI  - Establishment of novel detection system for embryonic stem cell-derived
      hepatocyte-like cells based on nongenetic manipulation with indocyanine green.
AB  - Hepatocytes derived from embryonic stem cells (ESCs) are expected to be useful
      for basic research and clinical applications. However, in several studies,
      genetic methods used to detect and obtain them are difficult and pose major
      safety problems. Therefore, in this study, we established a novel detection
      system for hepatocytes by using indocyanine green (ICG), which is selectively
      taken up by hepatocytes, based on nongenetic manipulation. ICG has maximum light
      absorption near 780 nm, and it fluoresces between 800 and 900 nm. Making use of
      these properties, we developed flow cytometry equipped with an excitation lazer
      of 785 nm and specific bandpass filters and successfully detected ESC-derived ICG
      positive cells that were periodic acid-Schiff positive and expressed hepatocyte
      phenotypic mRNAs. These results demonstrate that this detection system based on
      nongenetic manipulation with ICG will lead to isolate hepatocytes generated from
      ESCs and provide the appropriate levels of stability, quality, and safety
      required for cell source for cell-based therapy and pharmaceutical studies such
      as toxicology.

PMID- 21902620
TI  - Gut flora may offer new therapeutic targets for the traditional Chinese medicine
      enteric dialysis.

PMID- 21902619
TI  - Evaluation of a thin and mechanically stable collagen cell carrier.
AB  - The biological function of adherent cell populations strongly depends on the
      physical and biochemical properties of extracellular matrix molecules. Therefore,
      numerous biocompatible cell carriers have been developed to specifically
      influence cell attachment, proliferation, cellular differentiation, and tissue
      formation for diverse cell culture applications and cell-based therapies. In the
      present study, we evaluated the mechanical and the cell biological properties of
      a novel, thin, and planar collagen scaffold. The cell carrier is based on
      fibrillar bovine collagen type I and exhibits a low material thickness coupled
      with a high mechanical stability as measured by tensile tests. The influence of
      this new biomaterial on cell viability, proliferation, and cell differentiation
      was analyzed using 5-bromo-2-deoxyuridine (BrdU) proliferation assay,
      immunocytochemistry, water-soluble tetrazolium salt-1 assay (WST-1), live cell
      imaging, and electron microscopy. Cell culture experiments with the human
      osteosarcoma cell line Saos-2, human mesenchymal stem cells, and rodent
      cardiomyocytes demonstrated the in vitro biocompatibility of this chemically
      noncrosslinked scaffold. Both the mechanical characteristics and the in vitro
      biocompatibility of this collagen type I carrier facilitate the engineering of
      thin transferable tissue constructs and offer new possibilities in the fields of
      cell culture techniques, tissue engineering, and regenerative medicine.

PMID- 21902621
TI  - Long-term efficacy, safety, and tolerability of rilpivirine (RPV, TMC278) in HIV
      type 1-infected antiretroviral-naive patients: week 192 results from a phase IIb
      randomized trial.
AB  - TMC278-C204 (NCT00110305), a 96-week trial of the nonnucleoside reverse
      transcription inhibitor (NNRTI) rilpivirine (RPV, TMC278) in 368 HIV-1-infected,
      treatment-naive patients, was extended to investigate long-term safety and
      efficacy. Week 192 analysis results are presented. This was a long-term follow-up
      of a Phase IIb, randomized trial. No significant RPV dose-response relationships
      with respect to the primary endpoint (composite ITT-TLOVR algorithm) were
      observed at week 48 or 96. All RPV-treated patients were switched to open-label
      75 mg qd at week 96 and then to 25 mg qd, the Phase III dose, at approximately
      week 144 as it gave the best benefit-risk balance. All control patients continued
      receiving open-label efavirenz (EFV) 600 mg qd. At week 192, 59% of RPV- and 61%
      of EFV-treated patients maintained confirmed viral load <50 copies/ml (ITT-TLOVR
      algorithm). The mean changes from baseline in CD4 cell count were similar in both
      groups (RPV: 210 cells/mm(3) vs. EFV: 225 cells/mm(3)). No new safety concerns
      were noted between week 48 and 192. In the week 192 analysis, RPV compared with
      EFV was associated with a lower overall incidence of grade 2-4 adverse events
      (AEs) at least possibly related to treatment, including rash (p<0.001) and
      neurologic AEs (p<0.05 Fisher's exact test, post hoc analyses) Incidences of
      serious AEs, grade 3 or 4 AEs, and discontinuations due to AEs were similar
      across groups. Increases in total cholesterol, LDL-cholesterol, HDL-cholesterol,
      and triglycerides were significantly lower with RPV than with EFV. RPV continued
      to show sustained efficacy similar to EFV at week 192 with a generally more
      favorable safety profile.

PMID- 21902623
TI  - Fabrication of large pores in electrospun nanofibrous scaffolds for cellular
      infiltration: a review.
AB  - In the past decade, considerable effort has been made to construct biomimetic
      scaffolds from electrospun nanofibers for engineering different tissues. However,
      one of the major concerns with electrospun nanofibrous scaffolds is that the
      densely arranged architecture of fibers and small pores or voids between fibers
      hinder efficient cellular infiltration or prevent three dimensional (3D) cellular
      integration with host tissue in vivo after implantation. To overcome this
      problem, many concepts or strategies applicable during the electrospinning or
      post-electrospinning procedures have been proposed to enlarge pore size of
      electrospun scaffolds. This article addresses the issues of pore geometry and
      cellular infiltration of electrospun scaffolds, and first reviews the fabrication
      solutions/approaches applied to achieve larger micropores in electrospun mats.
      The evidence and potential for fostering cellular infiltration using these
      improved porous scaffolds are then discussed. Finally, it is hoped that this will
      enable us to better exploit viable technologies or develop new ones for
      constructing ideal nanofibrous architecture for fulfilling specific tissue
      engineering needs.

PMID- 21902622
TI  - Bone tissue engineering bioreactors: a role in the clinic?
AB  - Tissue engineered bone grafts have the potential to be used to treat large bone
      defects due to congenital abnormalities, cancer resections, or traumatic
      incidents. Recent studies have shown that perfusion bioreactors can be used to
      generate grafts of clinically relevant sizes and shapes. Despite these scientific
      and technological successes, there is uncertainty regarding the translational
      utility of bioreactor-based approaches due to the perceived high costs associated
      with these procedures. In fact, experiences over the past two decades have
      demonstrated that the widespread application of cell-based therapies is heavily
      dependent on the commercial viability. In this article, we directly address the
      question of whether bioreactors used to create bone grafts have the potential to
      be implemented in clinical approaches to bone repair and regeneration. We provide
      a brief review of tissue engineering approaches to bone repair, clinical trials
      that have employed cell-based methods, and advances in bioreactor technologies
      over the past two decades. These analyses are combined to provide a perspective
      on what is missing from the scientific literature that would enable an objective
      baseline for weighing the benefit of extended in vitro cultivation of cells into
      functional bone grafts against the cost of additional cultivation. In our
      estimation, the cost of bioreactor-based bone grafts may range from $10,000 to
      $15,000, placing it within the range of other widely used cell-based therapies.
      Therefore, in situations where a clear advantage can be established for
      engineered grafts comprising patient-specific, autologous cells, engineered bone
      grafts may be a clinically feasible option.

PMID- 21902624
TI  - ATP-adenosine-glutathione cross-linked hemoglobin as clinically useful oxygen
      carrier.
AB  - To attenuate hemoglobin's (Hb) intrinsic toxicity, Texas Tech University
      scientists developed a novel concept of "pharmacologic cross-linking" to
      formulate an effective oxygen carrier, HemoTech, which consists of purified
      bovine Hb cross-linked intramolecularly with ATP and intermolecularly with
      adenosine, and conjugated with reduced glutathione (GSH). In this composition,
      while ATP prevents Hb dimerization, adenosine permits the formation of
      homogeneous polymers. ATP also serves as a regulator of blood vessel tone via
      activation of the P2Y receptor, whereas adenosine counteracts the
      vasoconstrictive and pro-inflammatory properties of Hb via stimulation of
      adenosine A2 and A3 receptors. GSH introduces electronegative charge onto the Hb
      surface that blocks Hb's transglomerular and transendothelial passage. Besides,
      GSH shields heme from nitric oxide and reactive oxygen species, thus enhancing
      vasodilation and lowering Hb prooxidative potential. HemoTech underwent favorable
      initial pre-clinical testing and proof of medical concept, and is under
      commercial development by HemoBioTech Inc. HemoTech has entered the regulatory
      process in the US. Several mandated requirements have already been met, including
      viral/transmissible spongiform encephalopathy (TSE) clearance validation studies
      and various pre-clinical pharmacological, pharmacokinetic, toxicological,
      genotoxicity and efficacy tests. These studies provided further evidence that
      "pharmacologic cross-linking" of the Hb molecule with ATP, adenosine and GSH, is
      useful for designing a viable Hb-based oxygen carrier.

PMID- 21902625
TI  - Searching for artemisinin production improvement in plants and microorganisms.
AB  - The endoperoxide sesquiterpene lactone artemisinin which is isolated from the
      plant Artemisia annua, and its semi-synthetic derivatives, are potent, novel,
      antimalarial drugs. They are effective against multidrug-resistant Plasmodium
      strains and have become essential components of the so-called Artemisinin-based
      Combination Therapy, that is recommended by the World Health Organization as the
      treatment of choice for malaria tropica. Moreover, artemisinin and its
      derivatives show additional anti-parasite, antitumor, and anti-viral properties.
      The plants, however, are very poor resources for the drug, as the content of
      artemisinin is low (from 0,1 to 1,5 % of dried leaves) and dependent on seasonal
      and somatic variations as well as the infestation of bacteria, fungi and insects.
      A chemical synthesis of the compound is complex and uneconomic. Therefore,
      artemisinin is in short supply and remains unaffordable for most people in
      malaria-endemic countries. Thus, many researchers have focused on enhancing the
      production of artemisinin, first, through traditional breeding and in in vitro
      plant tissue cultures and, then, by heterologous expression systems (a semi
      synthetic approach) with the use of genetically-modified or transgenic microbes.
      In this review, we summarize the progress made in the production of artemisinin
      by the biotechnological approach.

PMID- 21902626
TI  - Substrate reduction therapies for mucopolysaccharidoses.
AB  - Mucopolysaccharidoses (MPS) are inherited metabolic disorders, caused by
      mutations leading to dysfunction of one of enzymes involved in degradation of
      glycosaminoglycans (GAGs) in lysosomes. Due to their impaired degradation, GAGs
      accumulate in cells of patients, which results in dysfunction of tissues and
      organs, including the heart, respiratory system, bones, joints and central
      nervous system. Depending on the kind of deficient enzyme, 11 types and subtypes
      of MPS are currently recognized. Although enzyme replacement therapy has been
      developed for 3 types of MPS (types I, II and VI), this treatment was found to be
      effective only in management of somatic symptoms. Since all MPS types except IVA,
      IVB and VI are characterized by various problems with functioning of the central
      nervous system (CNS), a search for effective treatment of this system is highly
      desirable. Recent discoveries suggested that substrate reduction therapy may be
      an efficient method for treatment of MPS patients, including their CNS. In this
      review, different variants of this therapy will be discussed in the light of
      recently published reports.

PMID- 21902627
TI  - Targeting stenosis with nucleotide-hydrolyzing enzymes.
AB  - Well-established evidence links extracellular nucleotides to numerous vascular
      pathologies, including restenosis associated with angioplasty, atherosclerosis
      and transplant arteriosclerosis. Through activation of purinergic P2 receptors,
      extracellular nucleotides contribute to the pathogenesis of occlusive vascular
      diseases by mediating thrombosis, and vascular smooth muscle proliferation and
      migration. Therefore, there is a growing interest in the enzymes that hydrolyze
      nucleotides for their capability to modulate nucleotide-triggered pathologies. In
      this review, we present the current data addressing the therapeutic potential of
      nucleoside triphosphate diphosphohydrolases (NTPDases) to prevent intimal
      hyperplasia and treat vascular intimal disease. In addition, we discuss the
      mechanisms by which NTPDases exert protective effects in vascular function.

PMID- 21902628
TI  - O-aminoacylation of bacterial glycoconjugates: from native structure to vaccine
      design.
AB  - The aminoacylation of bacterial polysaccharide antigens and its biological role
      are poorly understood, although it might be relevant in infection and immunity.
      Due to the lability of ester-linked substituents on glycoconjugate antigens, such
      groups usually escape detection during routine structural investigation. Of the
      few data available, those on the occurrence of glycine in the endotoxic
      lipopolysaccharides of Gram-negative bacteria are well documented. This article
      summarizes these data on glycine as an integral constituent of bacterial LPS and
      also some other amino-acid esters in the teichoic acids and phosphatidylglycerol
      of Gram-positive bacteria. The possible functions of such noncarbohydrate ester
      linked substituents in bacterial antigens are discussed. Because glycine, an
      inherent component of bacterial lipopolysaccharides in the core region, is
      supposed to participate in epitope formation, such a structure may be considered
      for potential use in the construction of a vaccine with broad specificity.

PMID- 21902629
TI  - Advanced trans-epithelial drug delivery devices.
AB  - The presented paper describes the drug delivery devices which can be considered
      as advanced or potentially "intelligent". Due to the current development state
      and the legal problems of implantable drug releasing electronic devices the
      review is limited to the systems which delivers drugs through the skin or mucosa.
      The article shows the principle of operation and some construction details of
      such devices. It also discusses the possible methods of sampling body fluids
      across the drug delivery barriers to introduce a feedback loop which is necessary
      to react on the metabolic process in the human body and their malfunctioning. In
      the near future presented devices will evolve towards the highly sophisticated
      systems which will monitor our metabolism and deliver necessary drugs and
      hormones in the precisely calculated doses to regulate our body functions without
      absorbing our attention.

PMID- 21902630
TI  - Progress in nanoparticulate systems for peptide, proteins and nucleic acid drug
      delivery.
AB  - Progress in many therapies, in particular in the therapies based on peptides,
      proteins and nucleic acids used as bioactive compounds, strongly depends on
      development of appropriate carriers which would be suitable for controlled
      delivery of the intact abovementioned compounds to required tissues, cells and
      intracellular compartments. This review presents last ten years' achievements and
      problems in development and application of synthetic polymer nanoparticulate
      carriers for oral, pulmonary and nasal delivery routes of oligopeptides and
      proteins. Whereas some traditional synthetic polymer carriers are only briefly
      recalled the main attention is concentrated on nanoparticles produced from
      functional copolymers mostly with hydroxyl, carboxyl and amino groups, suitable
      for immobilization of targeting moieties and for assuring prolonged circulation
      of nanoparticles in blood. Formulations of various nanoparticulate systems are
      described, including solid particles, polymer micelles, nanovesicles and
      nanogels, especially systems allowing drug release induced by external stimuli.
      Discussed are properties of these species, in particular stability in buffers and
      models of body fluids, loading with drugs and with drug models, drug release
      processes and results of biological studies. There are also discussed systems for
      gene delivery with special attention devoted to polymers suitable for compacting
      nucleic acids into nanoparticles as well as the relations between chemical
      structure of polymer carriers and ability of the latter for crossing cell
      membranes and for endosomal escape.

PMID- 21902631
TI  - Mechanisms involved in the development of chronic hepatitis C as potential
      targets of antiviral therapy.
AB  - At present, about 3% of the human population are infected with hepatitis C virus
      (HCV). The first, acute stage of the disease is usually asymptomatic. However,
      only 15-25% of the infected eliminate the virus, while the remaining patients
      develop chronic hepatitis C (CHC). After 10-30 years of CHC, cirrhosis occurs in
      20-30% of patients; 5-10% of this group eventually suffer from hepatocellular
      carcinoma. Unfortunately, up till now no effective methods protecting against HCV
      or allowing for efficient CHC treatment have been elaborated. This is primarily
      because not much is known about the mechanism of CHC emergence and the factors
      affecting anti-HCV therapy. There are several lines of evidence that some
      specific features of the virus, especially its high genetic variability might be
      responsible for the maintenance of HCV infection. Moreover, a few mechanisms
      which affect host-virus interactions and can additionally support CHC development
      have recently been identified. Hybridization between the host-encoded, liver
      specific microRNA (miR-122) and the 5'-untranslated region of HCV genome was
      shown to be required for effective viral RNA replication. It was also postulated
      that HCV proteins mimic some of the human ones; that is why the virus is not
      eliminated. Another hypothesis assumes that interactions between HCV E2
      glycoprotein and CD81 receptor modulate various cellular pathways, thus
      supporting viral propagation. There is no doubt that a better understanding of
      the mechanisms described above is of great importance for designing new
      therapeutic strategies and anti-HCV drugs.

PMID- 21902632
TI  - Nucleic acid-based technologies in therapy of malignant gliomas.
AB  - Malignant gliomas are the deadliest brain tumors, which are characterized by
      highly invasive growth, a rampant genetic instability and intense resistance to
      apoptosis. Such an aggressive behavior of malignant gliomas is reflected in the
      resistance to chemo- and radiotherapy and weak prognosis in spite of
      cytoreduction through surgery. Brain tumors preferentially express a number of
      specific protein and RNA markers, that may be exploited as potential therapeutic
      targets in design of the new treatment modalities based on nucleic acids. For
      almost three decades, a possibility to apply DNA and RNA molecules as anticancer
      therapeutics have been studied. A variety of antisense oligonucleotides,
      ribozymes, DNAzymes, and aptamers can be designed to trigger the sequence
      specific inhibition of particular mRNA of interest. RNA interference (RNAi) is
      the latest and the most promising technique in the long line of nucleic acid
      based therapeutic technologies. Recently, we designed and implemented the
      experimental therapy of patients suffering from malignant brain tumors based on
      application of double-stranded RNA (dsRNA) specific for tenascin-C (TN-C) mRNA.
      That therapeutic agent, called ATN-RNA, induces RNAi pathway to inhibit the
      synthesis of TN-C, the extracellular matrix protein which is highly overexpressed
      in brain tumor tissue. In the chapter specific problems of application of nucleic
      acid-based technologies in glioma tumors treatment will be discussed.

PMID- 21902633
TI  - Bone tissue engineering - a field for new medicinal products?
AB  - It was only in December 2008 that the European Union regulated the approval
      procedure for tissue engineered products (TEPs). Due to this regulation, TEP is
      classified as an advanced therapy medicinal product and as such may be recognized
      as a tool in pharmaceutical biotechnology. This paper gives a short review of the
      concept, the experimental evaluation and the clinical potency of tissue
      engineering (TE), with a particular focus on bone tissue engineered products.
      After a period of great enthusiasm about TE at the end of the 20th century a
      slight disappointment followed in the early 2000s. The review refers also to the
      continuously growing scientific interest, accompanied by the still modest
      representation of TEPs on the medical market. Some remarks are given on a bench
      to-clinic road, including criticism concerning data originating from animal
      experiments. An attempt is made to foresee the still promising future of bone
      tissue engineered products (BTEPs) in practical use.

PMID- 21902634
TI  - Tailoring small proteins towards biomedical applications.
AB  - Over the last two decades proteins have become increasingly important in human
      therapy and diagnosis. Engineering therapeutic proteins through improving their
      biological activity and stability has been a major interest in our group. In this
      mini-review we summarize our research on three proteins with pharmaceutical
      potential - serine protease inhibitor from squash seeds (CMTI), bovine pancreatic
      trypsin inhibitor (BPTI), and human fibroblast growth factor 1 (FGF1). To improve
      the functional properties of these proteins we used multiple techniques such as
      homology approach, rational design, total chemical synthesis, site-directed
      mutagenesis and phage display. The physicochemical properties of the obtained
      protein variants were evaluated using protein crystallography, spectroscopic
      techniques, enzymatic assays, stability measurements as well as numerous
      biological tests.

PMID- 21902635
TI  - Stem cells in pharmaceutical biotechnology.
AB  - Multiple populations of stem cells have been indicated to potentially participate
      in regeneration of injured organs. Especially, embryonic stem cells (ESC) and
      recently inducible pluripotent stem cells (iPS) receive a marked attention from
      scientists and clinicians for regenerative medicine because of their high
      proliferative and differentiation capacities. Despite that ESC and iPS cells are
      expected to give rise into multiple regenerative applications when their side
      effects are overcame during appropriate preparation procedures, in fact their
      most recent application of human ESC may, however, reside in their use as a tool
      in drug development and disease modeling. This review focuses on the applications
      of stem cells in pharmaceutical biotechnology. We discuss possible relevance of
      pluripotent cell stem populations in developing physiological models for any
      human tissue cell type useful for pharmacological, metabolic and toxicity
      evaluation necessary in the earliest steps of drug development. The present
      models applied for preclinical drug testing consist of primary cells or
      immortalized cell lines that show limitations in terms of accessibility or
      relevance to their in vivo counterparts. The availability of renewable human
      cells with functional similarities to their in vivo counterparts is the first
      landmark for a new generation of cell-based assays. We discuss the approaches for
      using stem cells as valuable physiological targets of drug activity which may
      increase the strength of target validation and efficacy potentially resulting in
      introducing new safer remedies into clinical trials and the marketplace.
      Moreover, we discuss the possible applications of stem cells for elucidating
      mechanisms of disease pathogenesis. The knowledge about the mechanisms governing
      the development and progression of multitude disorders which would come from the
      cellular models established based on stem cells, may give rise to new
      therapeutical strategies for such diseases. All together, the applications of
      various cell types derived from patient specific pluripotent stem cells may lead
      to targeted drug and cellular therapies for certain individuals.

PMID- 21902636
TI  - Application of baculovirus-insect cell expression system for human therapy.
AB  - A major advantage of recombinant DNA technology is its flexibility allowing for
      "on demand" production of specific proteins with theurapeutic value in
      heterologous expression systems. Gene expression vectors based on baculovirus,
      insect virus attacking mostly lepidopteran species, are frequently used for
      relatively inexpensive and fast production of such proteins. This expression
      system is recognized as one of the most powerful technologies for commercial
      synthesis of glycoproteins originating from vertebrate themselves or from
      vertebrate viruses. Glycosylation pathways utilized by insects are not identical,
      though they are similar to vertebrate glycosylation pathways. In the review
      special attention is given to the development of new virus-like particles (VLPs)
      potential vaccines which represent a novel class of subunit vaccines that are
      able to stimulate efficiently cellular and humoral immune responses against viral
      agents. Apart from production of vertebrate proteins or VLPs  "on demand " in
      insect cells, a new exciting field of using baculovirus as gene delivery system
      to vertebrate cells was recently open which has a great potential for future uses
      of baculovirus as effective gene therapy vector.

PMID- 21902637
TI  - Polish.

PMID- 21902638
TI  - High throughput applications in green chemistry.

PMID- 21902639
TI  - Implementation of high throughput experimentation techniques for kinetic reaction
      testing.
AB  - Successful implementation of High throughput Experimentation (EE) tools has
      resulted in their increased acceptance as essential tools in chemical,
      petrochemical and polymer R&D laboratories. This article provides a number of
      concrete examples of EE systems, which have been designed and successfully
      implemented in studies, which focus on deriving reaction kinetic data. The
      implementation of high throughput EE tools for performing kinetic studies of both
      catalytic and non-catalytic systems results in a significantly faster acquisition
      of high-quality kinetic modeling data, required to quantitatively predict the
      behavior of complex, multistep reactions.

PMID- 21902640
TI  - Accelerating research into bio-based FDCA-polyesters by using small scale
      parallel film reactors.
AB  - High Throughput experimentation has been well established as a tool in early
      stage catalyst development and catalyst and process scale-up today. One of the
      more challenging areas of catalytic research is polymer catalysis. The main
      difference with most non-polymer catalytic conversions is the fact that the
      product is not a well defined molecule and the catalytic performance cannot be
      easily expressed only in terms of catalyst activity and selectivity. In
      polymerization reactions, polymer chains are formed that can have various lengths
      (resulting in a molecular weight distribution rather than a defined molecular
      weight), that can have different compositions (when random or block co-polymers
      are produced), that can have cross-linking (often significantly affecting
      physical properties), that can have different endgroups (often affecting
      subsequent processing steps) and several other variations. In addition, for
      polyolefins, mass and heat transfer, oxygen and moisture sensitivity,
      stereoregularity and many other intrinsic features make relevant high throughput
      screening in this field an incredible challenge. For polycondensation reactions
      performed in the melt often the viscosity becomes already high at modest
      molecular weights, which greatly influences mass transfer of the condensation
      product (often water or methanol). When reactions become mass transfer limited,
      catalyst performance comparison is often no longer relevant. This however does
      not mean that relevant experiments for these application areas cannot be
      performed on small scale. Relevant catalyst screening experiments for
      polycondensation reactions can be performed in very efficient small scale
      parallel equipment. Both transesterification and polycondensation as well as post
      condensation through solid-stating in parallel equipment have been developed.
      Next to polymer synthesis, polymer characterization also needs to be accelerated
      without making concessions to quality in order to draw relevant conclusions.

PMID- 21902641
TI  - Oxidative homocoupling of alkynes using supported ionic liquid phase (SILP)
      catalysts--systematic investigation of the support influence.
AB  - Supported Ionic Liquid Phase (SILP) catalysts have been prepared by effective
      immobilization of [Cu(TMEDA)(OH)]Cl in a nano-metric film of an ionic liquid on
      various oxidic support materials. The catalysts were tested for the oxidative
      homocoupling of 1-alkynes to the corresponding diynes in in a combined high
      throughput and conventional batch reaction approach. Among the screened support
      materials silica based materials performed best. The results indicate that for
      the specific reaction the thickness of the ionic liquids layer and therefore the
      mobility of the homogeneous copper complex within the ionic liquid layer as
      deduced from solid state nmr measurements have major impact on the catalytic
      performance. The optimized catalysts could be recycled up to four times without
      any loss of activity.

PMID- 21902642
TI  - Combinatorial synthesis and characterization of metal-open frameworks in mild and
      friendly conditions: application to CO2 adsorption.
AB  - Combinatorial screening using precipitation methods at room temperature can lead
      to a great diversity of carboxylate based Metal Organic Frameworks (MOFs)
      including already known or original porous solids. The investigation of the
      synthesis of MOFs in different solvent and solvent mixtures includes the use of
      solvents such as alcohols and tetrahydrofuran (THF) which would greatly
      facilitate large scale production. We also show the application of Principal
      Component Analysis (PCA) and clustering techniques on large libraries of XRD
      diffraction files in order to identify classes of similar phases and peculiar
      phases. The combinatorial screening of 105 samples in the La/btc system has led
      to the identification of two phases which are solvent depending. On the La(btc)
      compound, the CO2 adsorption measurements reveal a guest-host interactions as
      supported by XRD phase transformation upon thermal treatment. The mass transport
      can be assigned to a "single file diffusion" regime due to the one dimensional
      channel porous structure associated to small pore size.

PMID- 21902643
TI  - Transition-metal-free catalysts for the sustainable epoxidation of alkenes: from
      discovery to optimisation by means of high throughput experimentation.
AB  - Transition-metal-free oxides were studied as heterogeneous catalysts for the
      sustainable epoxidation of alkenes with aqueous H2O2 by means of high throughput
      experimentation (HTE) techniques. A full-factorial HTE approach was applied in
      the various stages of the development of the catalysts: the synthesis of the
      materials, their screening as heterogeneous catalysts in liquid-phase epoxidation
      and the optimisation of the reaction conditions. Initially, the chemical
      composition of transition-metal-free oxides was screened, leading to the
      discovery of gallium oxide as a novel, active and selective epoxidation catalyst.
      On the basis of these results, the research line was continued with the study of
      structured porous aluminosilicates, gallosilicates and silica-gallia composites.
      In general, the gallium-based materials showed the best catalytic performances.
      This family of materials represents a promising class of heterogeneous catalysts
      for the sustainable epoxidation of alkenes and offers a valid alternative to the
      transition-metal heterogeneous catalysts commonly used in epoxidation. High
      throughput experimentation played an important role in promoting the development
      of these catalytic systems.

PMID- 21902644
TI  - Catalyst optimization strategy: selective oxidation of o-xylene to phthalic
      anhydride.
AB  - The oxidation of o-xylene and/or naphthalene to phthalic anhydride is one of the
      important industrial processes based on catalytic selective oxidation reactions.
      Vanadia--titania catalysts have been used in the industrial phthalic anyhdride
      process for the last 50 years. The operation parameters like the temperature
      range of operation, reactor inlet pressures, contact times, o-xylene loadings,
      etc. were constantly improved during this period of continuous process
      optimization so as to optimize catalyst performance and increase its life time.
      However, a fundamental understanding of the mutual interaction of the rather
      complex reaction network and the catalyst formulation is still missing. Recently,
      a detailed study of by-product formation as function of process conditions
      allowed us to develop a novel, improved reaction scheme for the catalytic
      oxidation of o-xylene. Based on this understanding, a detailed investigation was
      conducted for the first time of the by-product formation under varying operation
      conditions and as a function of the active mass variation exploiting high
      throughput, as well as bench scales reactors. This high-throughput testing
      allowed us to relate reaction kinetics to novel catalyst formulations.

PMID- 21902645
TI  - Valorisation of glycerol as renewable feedstock: comparison of the exploration of
      chemical transformation methods aided by high throughput experimentation.
AB  - Renewable feedstocks have been in the spotlight of intensive research activities
      over the past 10 years. Glycerol is one of the feedstock molecules which has been
      the target of numerous research efforts, for a number of reasons. First of all
      glycerol is currently readily available due to the fact that it is a couple
      product of the first generation biodiesel production. Secondly glycerol can be
      taken as a representative model substrate to explore the options of selective
      conversion of sugar alcohols to products of value. In our paper we discuss
      potential routes for the valorisation of glycerol which lead to intermediates
      already established within the petrochemical value chain and illustrate what
      impact high throughput experimentation may have as a success factor on research
      and development for this field. As illustrative examples we have chosen the
      oxidative transformation of glycerol to acrolein and acrylic acid and the
      carbonylation of glycerol to C4-acids.

PMID- 21902646
TI  - High throughput development of selective oxidation catalysts at Sud-Chemie.
AB  - The Temkin reactor concept was successfully extended to the high throughput
      operation mode and it could be considerably improved as compared to the original
      design with respect to an optimized gas flow pattern over the full size beads.
      This improved parallel reactor design was successfully used for the high
      throughput optimization of an innovative new class of physically coated VAM shell
      catalysts. Exploiting this novel, improved Temkin reactor concept allowed Sud
      Chemie not only to optimize the multiparameter compositional space of noble metal
      and promoter loadings on the support spheres but for the first time to combine
      this "chemical optimization" with the high throughput improvement of
      catalytically decisive parameters as the active shell thickness, the metal
      distribution cross the shell, the pore diameters, and the pore volumes. This new
      class of physically impregnated VA catalysts, called VAM2ax, impress by its
      exceptionally high VA selectivity of above 94% at 50% oxygen conversion and the
      very high space time yields of > 1000 g VAM/l*h which easily can be reached over
      these shell catalysts with optimized mass and heat transport properties.

PMID- 21902647
TI  - Synergism between constituents of multicomponent catalysts designed for ethanol
      steam reforming using partial least squares regression and artificial neural
      networks.
AB  - Effects of different catalyst components on the catalytic performance in steam
      reforming of ethanol have been investigated by means of Artificial Neural
      Networks (ANNs) and Partial Least Square regression (PLSR). The data base
      consisted of ca. 400 items (catalysts with varied composition), which were
      obtained from a former catalyst optimization procedure. Marten's uncertainty
      (jackknife) test showed that simultaneous addition of Ni and Co has crucial
      effect on the hydrogen production. The catalyst containing both Ni and Co
      provided remarkable hydrogen production at 450 degrees C. The addition of Ceas
      modifier to the bimetallic NiCo catalyst has high importance at lower
      temperatures: the hydrogen concentration is doubled at 350 degrees C. Addition of
      Pt had only little effect on the product distribution. The outliers in the data
      set have been investigated by means of Hotelling T2 control chart. Compositions
      containing high amount of Cu or Ce have been identified as outliers, which points
      to the nonlinear effect of Cu and Ce on the catalytic performance. ANNs were used
      for analysis of the non-linear effects: an optimum was found with increasing
      amount of Cu and Ce in the catalyst composition. Hydrogen production can be
      improved by Ce only in the absence of Zn. Additionally, negative cross-effect was
      evidenced between Ni and Cu. The above relationships have been visualized in
      Holographic Maps, too. Although predictive ability of PLSR is somewhat worse than
      that of ANN, PLSR provided indirect evidence that ANNs were trained adequately.

PMID- 21902648
TI  - Cytogenetic and molecular abnormalities in myelodysplastic syndrome.
AB  - Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematological
      disorders characterized by ineffective hematopoiesis which causes peripheral
      cytopenias and a risk of progression to acute myeloid leukemia. Although various
      forms of chromosomal abnormalities have been detected in approximately 50-60% of
      patients with de novo MDS and in up to 80% of patients with therapy-related MDS,
      their molecular significance for pathogenesis and disease progression is not yet
      fully understood. Recent technical advances in molecular biology have disclosed
      more accurately details of pathological chromosomal and molecular aberrations in
      MDS. Such details could not be identified with conventional cytogenetical
      techniques, including G-banding. In particular, with recent technical advances in
      comparative genome hybridization or single nucleotide polymorphism array
      technology, several candidate genes for the pathogenesis of MDS have been
      identified, which are located in minimally deleted or uniparental disomy
      segments. Moreover, epigenetic deregulation of gene expression is also likely to
      be involved in the pathogenesis of MDS. Accordingly, in addition to classical
      oncogenic abnormalities, such as p53 abnormalities, or NRAS mutation, various
      molecular abnormalities, such as TET2, RPS14, or c-CBL, have been identified
      and/or proposed as the novel candidates for molecular basis of the development
      and progression of MDS. A better understanding of the causative molecular events
      underlying MDS pathogenesis is essential for the development and establishment of
      a more effective treatment resulting in a complete cure for MDS. We here review
      current knowledge regarding the molecular significance of chromosomal and genetic
      aberrations in MDS and the proposed molecular mechanisms of action of new agents
      for MDS, such as lenalidomide or azacitidine.

PMID- 21902649
TI  - Gastrointestinal immune system and brain dialogue implicated in neuroinflammatory
      and neurodegenerative diseases.
AB  - A common characteristic of the central nervous system (CNS) neurodegenerative
      disorders is neuroinflammation, marked by augmented numbers of activated and
      primed microglia, increased inflammatory cytokines and decreased anti
      inflammatory molecules. CNS neuroinflammation is a critical component in the
      progression of several neurodegenerative diseases which sensitize the brain to
      produce an exaggerated response to immune stimuli in the periphery.
      Neuroinflammation might initiate from the periphery and peripheral conditions
      through disrupted blood-brain barrier powerfully influence various brain
      pathologies. Gastrointestinal tract (GIT) represents a vulnerable area through
      which pathogens influence the brain and induce CNS neuroinflammation. The
      pathogens may access the CNS through blood, the nasal olfactory pathways and the
      GIT. Potential GI pathogens, such as Helicobacter pylori, induce humoral and
      cellular immune responses that, owing to the sharing of homologous epitopes
      (molecular mimicry), cross-react with CNS components thereby contributing and
      possibly perpetuating neural tissue damage. GIT is strictly connected to the CNS
      and a bi-directional communication exists between them. The brain is involved in
      regulating the immune and gut system. Conversely, limited attention has been paid
      on the GIT role in the development and regulation of the CNS autoimmune diseases.
      The GIT is the primary immune organ with specialized immunoregulatory and anti
      inflammatory functions, represented by the gastrointestinal immune system (GIS).
      This review focuses on the potential GIS and brain dialogue implicated in
      neurodegenerative diseases. Gaining a better understanding of the relationship
      between GIS and CNS could provide an insight on the pathogenesis and therapeutic
      strategies of these disorders.

PMID- 21902650
TI  - RAN GTPase as a target for cancer therapy: Ran binding proteins.
AB  - The identification of a relevant effector of Ran GTPase (Ran) signaling and its
      pathways could provide a novel approach to cancer therapeutics. With recent
      research highlighting the significant relationship between Ran expression and the
      occurrence and progression of cancer, the development of a small molecule
      compound that would decrease the endogenous levels of Ran in the cell would have
      anti-mitotic effects and could lead to the development of new types of cancer
      therapeutics. In the absence of Ran binding proteins, Ran is expected to remain
      locked up in non-productive complexes with importins and is effectively removed
      from the system. Thus, Ran binding proteins present as a logical molecular target
      for the inhibition of Ran signaling within the cancer cell. Moreover, this family
      of proteins has been shown to have various other functions within the cell, some
      of which are also anti-neoplastic. The purpose of this review is to discuss Ran
      binding proteins and how their pathways may be exploited to provide an effective
      cancer treatment.

PMID- 21902651
TI  - Xanthones from mangosteen extracts as natural chemopreventive agents: potential
      anticancer drugs.
AB  - Despite decades of research, the treatment and management of malignant tumors
      still remain a formidable challenge for public health. New strategies for cancer
      treatment are being developed, and one of the most promising treatment strategies
      involves the application of chemopreventive agents. The search for novel and
      effective cancer chemopreventive agents has led to the identification of various
      naturally occurring compounds. Xanthones, from the pericarp, whole fruit,
      heartwood, and leaf of mangosteen (Garcinia mangostana Linn., GML), are known to
      possess a wide spectrum of pharmacologic properties, including antioxidant, anti-
      tumor, anti-allergic, anti-inflammatory, anti-bacterial, anti-fungal, and anti
      viral activities. The potential chemopreventive and chemotherapeutic activities
      of xanthones have been demonstrated in different stages of carcinogenesis
      (initiation, promotion, and progression) and are known to control cell division
      and growth, apoptosis, inflammation, and metastasis. Multiple lines of evidence
      from numerous in vitro and in vivo studies have confirmed that xanthones inhibit
      proliferation of a wide range of human tumor cell types by modulating various
      targets and signaling transduction pathways. Here we provide a concise and
      comprehensive review of preclinical data and assess the observed anticancer
      effects of xanthones, supporting its remarkable potential as an anticancer agent.

PMID- 21902652
TI  - Molecular genetics and mechanisms of disease in distal hereditary motor
      neuropathies: insights directing future genetic studies.
AB  - The distal hereditary motor neuropathies (dHMNs) are a clinically and genetically
      heterogeneous group of disorders that primarily affect motor neurons, without
      significant sensory involvement. New dHMN genes continue to be identified. There
      are now 11 causative genes described for dHMN, and an additional five genetic
      loci with unidentified genes. This genetic heterogeneity has further delineated
      the classification of dHMN, which was previously classified according to mode of
      inheritance, age at onset, and additional complicating features. Some overlap
      between phenotypically distinct forms of dHMN is also apparent. The mutated genes
      identified to-date in dHMN include HSPB1, HSPB8, HSPB3, DCTN1, GARS, PLEKHG5,
      BSCL2, SETX, IGHMBP2, ATP7A and TRPV4. The pathogenesis of mutations remains to
      be fully elucidated, however common pathogenic mechanisms are emerging. These
      include disruption of axonal transport, RNA processing defects, protein
      aggregation and inclusion body formation, disrupted calcium channel activity, and
      loss of neuroprotective signalling. Some of these dHMN genes are also mutated in
      Charcot-Marie-Tooth (CMT) disease and spinal muscular atrophy (SMA). This review
      examines the growing number of identified dHMN genes, discusses recent insights
      into the functions of these genes and possible pathogenic mechanisms, and looks
      at the increasing overlap between dHMN and the other neuropathies CMT2 and SMA.

PMID- 21902653
TI  - Inhibitors of apoptosis proteins (IAPs) as potential molecular targets for
      therapy of hematological malignancies.
AB  - Apoptosis, a programmed cell death, plays a key role in the regulation of tissue
      homeostasis. However, impairment of its regulation may promote formation and
      progression of malignancy. An important part of the apoptotic machinery are the
      inhibitor of apoptosis protein (IAP) family, regulating caspase activity, cell
      division or cell survival pathways through binding to their baculovirus AIP
      repeat (BIR) domains and/or by their ubiquitin-ligase RING zinc finger (RZF)
      activity. The following IAPs have been described so far: NAIP (neuronal apoptosis
      inhibitory protein; BIRC1), cIAP1 and cIAP2 (cellular inhibitor of apoptosis 1
      and 2; BIRC2 and BIRC3, respectively), XIAP (X-chromosome binding IAP; BIRC4),
      survivin (BIRC5), BRUCE (Apollon; BIRC6), livin (BIRC7) and Ts-IAP (testis
      specific IAP; BIRC8). Several studies suggested a potential contribution of IAPs
      to oncogenesis and resistance to anti-tumor treatment. Increased IAP expression
      was found in variety of human cancers, including hematological malignancies, such
      as leukemias and B-cell lymphomas. A correlation between the progression of those
      diseases and high levels of survivin or XIAP has been reported. Overexpression of
      XIAP in acute myeloid leukemia or survivin in acute lymphoblastic leukemia and
      diffuse large B-cell lymphoma have been indicated as an unfavorable prognostic
      factors. Elevated cellular levels of cIAP1, cIAP2, XIAP and survivin correlated
      with a progressive course of chronic lymphocytic leukemia. Thus, targeting IAPs
      with small-molecule inhibitors by their antisense approaches or natural IAP
      antagonist mimetics, may be an attractive strategy of anti-cancer treatment. Such
      agents can either directly induce apoptosis of tumor cells or sensitize them to
      other cytotoxic agents, hence overcoming drug-resistance. This review
      demonstrates the current knowledge on IAP molecular biology, as well as the
      mechanisms of action and the development of IAP-targeting agents for treatment of
      hematological malignancies.

PMID- 21902654
TI  - Molecular pathogenesis of non muscle-invasive bladder cancer: implications for
      novel targeted therapies.
AB  - Approximately 70% to 80% of patients with urothelial carcinomas of the bladder
      are initially diagnosed with non-muscle invasive disease. Superficial, non-muscle
      invasive bladder cancers (NMIBCs) are managed with cystoscopic transurethral
      resection of all visible lesions followed by intravesical chemotherapy and/or
      immunotherapy. Despite this treatment, up to 70% of these tumors will recur
      within five years and 15% will ultimately progress to muscle-invasive disease,
      suggesting that novel therapeutic strategies are necessary. Recent studies have
      greatly advanced our understanding of urothelial carcinogenesis and have
      highlighted the distinct molecular pathogenesis of NMIBCs versus muscle-invasive
      bladder tumors. It is now clear that diverse genetic and epigenetic events are
      driving the oncogenesis of NMIBCs, thereby attesting to their potential as
      therapeutic targets for these tumors. This article reviews the molecular
      pathogenesis of NMIBCs, discusses recently completed and ongoing clinical trials
      and anticipates the future direction of molecular targeted agents in this
      disease.

PMID- 21902655
TI  - Optimal medical therapy for coronary artery disease in 2011 - perspectives from
      the STICH Trial.
AB  - Medical, percutaneous interventional, and surgical treatments for the management
      of coronary heart disease have progressed markedly during the past decade. There
      is evidence to suggest that for patients with stable coronary heart disease
      optimal medical therapy is equal in effectiveness for lowering the risk of major
      cardiovascular events, such as cardiovascular death, myocardial infarction, and
      stroke, as are revascularization procedures, such as coronary artery bypass
      grafting or percutaneous coronary intervention. The landmark Surgical Treatment
      for Ischemic Heart Failure (STICH) trial found no significant difference between
      medical therapy alone and medical therapy plus coronary artery bypass grafting
      with respect to the primary end point of death from any cause (all-cause
      mortality). However, secondary outcomes showed fewer deaths from cardiovascular
      causes in the surgical group versus the medical group. Medical therapy has
      improved over time, as have surgical techniques including myocardial
      preservation, and both approaches have their place, especially since chest pain
      relief and quality of life may benefit more in some cases by revascularization.
      Certainly, coronary artery bypass grafting has general acceptance for three
      vessel coronary heart disease, and percutaneous coronary artery intervention is
      the standard of care for the involved artery in acute ST-segment elevation
      myocardial infarction when the intervention can be accomplished rapidly. Medical
      management includes lifestyle changes that benefit coronary heart disease, drug
      therapy to improve prognosis, and drug therapy to improve symptoms. The key to
      clinical management is the selection of the procedure and/or medical management
      strategy that is in the best interest of the individual cardiovascular patient.
      In addition, discussing with patients their options and considering what best
      fits their wishes is especially critical when there is no clear-cut best
      strategy. Continued collaboration between cardiologists concentrating on medical
      approaches with interventionists and cardiac surgeons (heart team approach) is
      essential for optimal management for each individual patient. 

PMID- 21902656
TI  - Current approaches to prevention of contrast induced acute kidney injury.
AB  - Contrast-induced acute kidney injury is one of the leading causes of hospital
      acquired acute kidney injury. Thus far, no strategies have been clearly shown to
      be effective in preventing contrast-induced acute kidney injury beyond thorough
      patient selection, meticulous hydration of the patient, and minimizing the amount
      of contrast used. Additional studies are needed to define the optimal means of
      hydration, role of commonly advocated prophylaxis strategies such as N
      acetylcysteine and develop newer more novel effective therapies to prevent or
      minimize the risk of kidney injury. 

PMID- 21902657
TI  - A review of oxidative stress related genes and new antioxidant therapy in
      diabetic nephropathy.
AB  - A genetic component of diabetes and its complications (including diabetic
      nephropathy (DN)) is obvious, but the causative genes and mechanisms have not yet
      been satisfactorily identified. Oxidative stress is a single mechanism relating
      all major pathways responsible for diabetic damage. Numerous oxidative stress
      related genes are positional candidates (determined by GWAS) and candidate genes
      studies confirm the association of their polymorphisms with DN. We present here
      their overview and connection to the "new antioxidant" therapy principle. 

PMID- 21902658
TI  - The effect of chronic co-administration of morphine and verapamil on
      isoproterenol-induced heart injury.
AB  - OBJECTIVE: Long-term co-administration of morphine and calcium channel
      antagonists (CCAs) is likely in some clinical conditions. Reciprocal interactions
      during chronic concomitant use of these agents are confirmed in central nervous
      system studies. However, there is little information regarding their chronic
      combination effects on the cardiovascular system. Present study was designed to
      assess the effects of chronic co-administration of morphine plus verapamil on
      some cardiovascular indices of rats with / without myocardial damage. METHODS:
      Animals were divided to control, morphine, verapamil and morphine plus verapamil
      groups each consisted of two subgroups, with and without heart injury. Rats were
      treated with increasing doses of morphine (10-20mg/kg, i.p.) or morphine plus
      verapamil (10mg/kg, i.p.) daily for 7 days. Heart injury was induced by
      isoproterenol (50 mg/kg, i.p.), then cardiac Troponin I was measured and on day
      8, blood pressure and heart rate was recorded and then the hearts were
      histopathologically examined. RESULTS: The results indicated that co
      administration of morphine with verapamil has stronger cardioprotective effect
      than morphine or verapamil alone as confirmed by the lower Troponin I level and
      myocardial lesion grades. However, no additional effects on mean arterial
      pressure and Rate-Pressure product were observed in combined use of these drugs.
      CONCLUSION: These findings suggest chronic co-administration of morphine and
      verapamil induced additive protective effects on rat heart exposed to myocardial
      injury comparing with each of them alone.

PMID- 21902659
TI  - Evaluation of a standardized protocol using lepirudin or argatroban for heparin
      induced thrombocytopenia.
AB  - STUDY OBJECTIVE: To evaluate the effectiveness of our institutions heparin
      induced thrombocytopenia (HIT) protocol in achieving a therapeutic activated
      partial thromboplastin time (aPTT) and to evaluate patient outcomes related to
      bleeding and thrombotic events before and after protocol implementation. DESIGN:
      Retrospective, single-center, pre- and post- assessment of a protocol previously
      approved at our institution. SETTING: 400-bed community hospital serving
      surrounding rural populations with emphasis in cardiothoracic surgery. PATIENTS:
      Retrospective chart review based on drug charge data identified 29 patients that
      received either argatroban or lepirudin for greater than 24 hours. Nineteen
      patients received either argatroban or lepirudin prior to HIT-protocol
      implementation, while the remaining ten received either drug after the HIT
      protocol was implemented. INTERVENTION: Implementation of HIT protocol occurred
      in March 2009. Patients were divided into pre-protocol and post-protocol groups.
      RESULTS: Primary outcome was to evaluate the number of therapeutic,
      subtherapeutic, and supratherapeutic aPTTs between two groups. In the pre
      protocol group, aPTTs were therapeutic, subtherapeutic, and supratherapeutic
      48.5% (164/338), 14.2% (48/338), and 37.2% (126/338) of the time, respectively.
      Meanwhile aPTTs in the post-protocol group were therapeutic, subtherapeutic, and
      supratherapeutic 46.6% (89/191), 22% (42/191), and 31.4% (60/191) of the time,
      respectively. The number of subtherapeutic aPTTs was statistically higher in the
      post-protocol group compared to the pre-protocol group. Secondary endpoints
      included the number of bleeding events and number of thrombotic events. None of
      the secondary endpoints reached statistical significance. Time to therapeutic
      aPTT was also evaluated: in the pre-protocol group median time (range) was 15
      hours (2-108.6) compared to 8.1 hours (2.3-94.2) in the post-protocol group.
      CONCLUSIONS: Adoption and implementation of HIT protocol at our institution
      resulted in significantly more subtherapeutic aPTTs as compared to time prior to
      protocol. Although not statistically significant, the time required to obtain
      therapeutic aPTT was reduced by almost 50% after protocol implementation, which
      could be of clinical importance. Larger studies are needed to continue to assess
      if standardized protocols are effective in treatment of HIT.

PMID- 21902660
TI  - Diabetic cardiomyopathy and oxidative stress: role of antioxidants.
AB  - Diabetes has emerged as a major threat to worldwide health. The increasing
      incidence of diabetes in young individuals is particularly worrisome given that
      the disease is likely to evolve over a period of years. In 1972, the existence of
      a diabetic cardiomyopathy was proposed based on the experience with four adult
      diabetic patients who suffered from congestive heart failure in the absence of
      discernible coronary artery disease, valvular or congenital heart disease,
      hypertension, or alcoholism. The exact mechanisms underlying the disease are
      unknown; however, there is growing evidence that excess generation of highly
      reactive free radicals, largely due to hyperglycemia, causes oxidative stress,
      which further exacerbates the development and progression of diabetes and its
      complications. Hyperglycemiainduced oxidative stress is a major risk factor for
      the development of micro-vascular pathogenesis in the diabetic myocardium, which
      results in myocardial cell death, hypertrophy, fibrosis, abnormalities of calcium
      homeostasis and endothelial dysfunction. In this review, we provide the emergence
      of experimental evidence supporting antioxidant supplementation as a
      cardioprotective intervention in the setting of diabetic cardiomyopathy. 

PMID- 21902661
TI  - Promising pharmacological, molecular and cellular treatments of autoimmune
      hepatitis.
AB  - Current corticosteroid regimens are effective in autoimmune hepatitis, but
      therapy can be complicated by side effects, disease progression, incomplete
      response, and relapse after drug withdrawal. The aims of this review are to
      describe the promising pharmacological, molecular and cellular interventions for
      autoimmune hepatitis and to stimulate further investigations that can refresh or
      replace current treatments. Murine models that introduce pertinent human disease
      related antigens by vaccination or viral infection promise a resource by which to
      evaluate new treatments. Promising new drug therapies include the calcineurin
      inhibitors (cyclosporine, tacrolimus), next generation purine antagonists
      (mycophenolate mofetil, 6-thioguanine nucleotides), next generation
      glucocorticoids (budesonide, deflazacort), and inhibitors of the mammalian target
      of rapamycin (rapamycin). Feasible molecular interventions are recombinant
      molecules that affect immune regulatory pathways (cytotoxic T lymphocyte antigen
      4, recombinant interleukin 10), monoclonal antibodies that disrupt activation
      pathways (antibodies to CD3, CD28, CD 20, or tumor necrosis factor-alpha), and
      synthetic peptides that block antigen display or promote antigen desensitization
      (oral tolerance). New methods to stimulate or replenish regulatory T cell
      populations (adoptive transfer, mesenchymal stem cell or autologous bone marrow
      transplantation) are feasible as are genetic manipulations (gene silencing) and
      gene supplementations (gene replacement therapy). The emergence of new therapies
      for autoimmune hepatitis requires a standardized and universalized animal model
      of the human disease, consensus regarding the most promising modality to be
      tested, and formation of a cooperative international network of committed
      clinical investigators to evaluate new therapies in a pre-designed rigorous yet
      expeditious fashion.

PMID- 21902663
TI  - Importance of iron chelation in free radical-induced oxidative stress and human
      disease.
AB  - Iron is a redox active metal involved in the oxidation-reduction reactions and
      regulation of cell growth and differentiation. Iron is an integral part of many
      proteins and enzymes that maintains various physiological functions. Most of the
      human body's iron is contained in red blood cells. Despite iron being an abundant
      trace metal in food, millions of people worldwide suffer from anemia. Iron
      deficiency results in impaired production of iron-containing proteins and
      inhibition of cell growth. In contrast, abnormal iron uptake has been related to
      the most common hereditary disease hemochromatosis, leading to tissue damage
      derived from free radical toxicity. In addition, disruption of iron regulation
      plays a key role in the etiology of Alzheimer's disease, Parkinson's disease,
      Huntington's disease, Friedreich's ataxia and other neurological disorders,
      cancer (lung cancer, breast cancer, colon cancer), Fanconi anemia, stroke and
      ageing. Thus the control of this necessary but potentially toxic substance is an
      important part of many aspects of human health and disease. The most frequent is
      the toxic role of iron linked with the catalytic decomposition of hydrogen
      peroxide (Fenton reaction) leading to the formation of reactive oxygen species
      (ROS) causing damage to biomolecules, including lipids, proteins and DNA. The
      binding of iron-designed chelators via nitrogen, oxygen or sulphur donor atoms
      blocks iron s ability to catalyze the formation of free radicals. Thus the design
      of various metal chelators to prevent free radical reactions is an important
      approach in the treatment of many iron-related diseases. The development of
      effective dual functioning antioxidants, possessing both metal-chelating and free
      radical-scavenging properties is awaited. The aim of this review is to discuss
      the role of iron and importance of iron-chelation in human disease and ageing.

PMID- 21902662
TI  - Targeting mitochondrial bioenergetics for Alzheimer's prevention and treatment.
AB  - Alzheimer's is a neurodegenerative disease with a complex and progressive
      pathological phenotype characterized first by hypometabolism and impaired
      mitochondrial bioenergetics followed by pathological burden. The progressive and
      multifaceted degenerative phenotype of Alzheimer's suggests that successful
      treatment strategies necessarily will be equally multi-faceted and disease stage
      specific. Traditional therapeutic strategies based on the pathological aspect of
      the disease have achieved success in preclinical models which has not translated
      into clinical therapeutic efficacy. Meanwhile, increasing evidence indicates an
      antecedent and potentially causal role of mitochondrial bioenergetic deficits and
      brain hypometabolism coupled with increased mitochondrial oxidative stress in AD
      pathogenesis. The essential role of mitochondrial bioenergetics and the unique
      trajectory of alterations in brain metabolic capacity enable a bioenergetic-
      centric strategy that targets disease-stage specific pattern of brain metabolism
      for disease prevention and treatment. A combination of nutraceutical and
      pharmaceutical intervention that enhances glucose-driven metabolic activity and
      potentiates mitochondrial bioenergetic function could prevent the antecedent
      decline in brain glucose metabolism, promote healthy aging and prevent AD.
      Alternatively, during the prodromal incipient phase of AD, sustained activation
      of ketogenic metabolic pathways coupled with supplement of the alternative fuel
      source, ketone bodies, could sustain mitochondrial bioenergetic function to
      prevent or delay further progression of the disease.

PMID- 21902664
TI  - Therapeutic intervention at cellular quality control systems in Alzheimer's and
      Parkinson's diseases.
AB  - Cellular homeostasis relies on quality control systems so that damaged biologic
      structures are either repaired or degraded and entirely replaced by newly formed
      proteins or even organelles. The clearance of dysfunctional cellular structures
      in long-lived postmitotic cells, like neurons, is essential to eliminate, per
      example, defective mitochondria, lipofuscin-loaded lysosomes and oxidized
      proteins. Short-lived proteins are degraded mainly by proteases and proteasomes
      whether most long-lived proteins and all organelles are digested by autophagy in
      the lysosomes. Recently, it an interplay was established between the ubiquitin
      proteasome system and macroautophagy, so that both degradative mechanisms
      compensate for each other. In this article we describe each of these clearance
      systems and their contribution to neuronal quality control. We will highlight
      some of the findings that provide evidence for the dysfunction of these systems
      in Alzheimer's and Parkinson's diseases. Ultimately, we provide an outline on
      potential therapeutic interventions based on the modulation of cellular
      degradative systems.

PMID- 21902665
TI  - Gene therapy for Parkinson's and Alzheimer's diseases: from the bench to clinical
      trials.
AB  - Alzheimer's and Parkinson's diseases represent the most prevalent
      neurodegenerative disorders worldwide. Current pharmacological or surgical
      treatments provide symptomatic benefits, particularly in the early stages, but
      none can delay or stop the progression of these diseases. There is an urgent need
      for new therapies able to modify disease progression. Gene therapy, mainly based
      on viral vectors, is presently being assumed as an important alternative to
      conventional treatments. After decades of preclinical developments, we are now
      facing an important period, in which several viral vector-mediated gene therapies
      are being tested in Phase 1 and Phase 2 clinical trials, with some of them
      showing promising results. This review intends to present an overview of the
      current efforts in the field for the treatment of Alzheimer's and Parkinson's
      diseases.

PMID- 21902666
TI  - Role of sirtuins and calorie restriction in neuroprotection: implications in
      Alzheimer's and Parkinson's diseases.
AB  - Aging is the major known risk factor for the onset of neurodegenerative diseases
      such as Alzheimer's disease (AD) and Parkinson's disease (PD). Mitochondria play
      a central role in aging as mitochondrial dysfunction increases with age and
      produces harmful levels of reactive oxygen species which leads to cellular
      oxidative stress (free-radical theory of aging). Oxidative stress is highly
      damaging to cellular macromolecules and is also a major cause of the loss and
      impairment of neurons in neurodegenerative disorders. A growing body of evidence
      suggests that modulation of sirtuin activity and restricting calorie intake has a
      strong neuroprotective effect. SIRT1 induction by the use of pharmacological
      activators or by calorie restriction (CR) diet regimen has been shown to protect
      against neuronal loss and impairment in the cellular and animal models of AD and
      PD. Here, we review the current knowledge and recent data related to the role of
      sirtuins and CR in neurodegeneration and discuss the potential underlying
      signaling pathways of neuroprotection that might serve as attractive targets for
      the future therapeutic intervention of these age-related neurodegenerative
      diseases.

PMID- 21902667
TI  - Microtubules (tau) as an emerging therapeutic target: NAP (davunetide).
AB  - This review focuses on the discovery of activity-dependent neuroprotective
      protein (ADNP) and the ensuing discovery of NAP (davunetide) toward clinical
      development with emphasis on microtubule protection. ADNP immunoreactivity was
      shown to occasionally decorate microtubules and ADNP silencing inhibited neurite
      outgrowth as measured by microtubule associated protein 2 (MAP2) labeling. ADNP
      knockout is lethal, while 50% reduction in ADNP (ADNP haploinsufficiency)
      resulted in the microtubule associated protein tau pathology coupled to cognitive
      dysfunction and neurodegeneration. NAP (davunetide), an eight amino acid peptide
      derived from ADNP partly ameliorated deficits associated with ADNP deficiency.
      NAP (davunetide) interacted with microtubules, protected against microtubule
      toxicity associated with zinc, nocodazole and oxidative stress in vitro and
      against tau pathology and MAP6 (stable tubuleonly polypeptide - STOP) pathology
      in vivo. NAP (davunetide) provided neurotrophic functions promoting neurite
      outgrowth as measured by increases in MAP2 immunoreactivity and synapse formation
      by increasing synaptophysin expression. NAP (davunetide) protection against
      neurodegeneration has recently been shown to extend to katanin-related
      microtubule disruption under conditions of tau deficiencies. In conclusion, NAP
      (davunetide) provided potent neuroprotection in a broad range of
      neurodegenerative models, protecting the neuroglial cytoskeleton in vitro and
      inhibiting tau pathology (tauopathy) in vivo. Based on these extensive
      preclinical results, davunetide (NAP) is now being evaluated in a Phase II/III
      study of the tauopathy, progressive supranuclear palsy (PSP); (Allon Therapeutics
      Inc.).

PMID- 21902668
TI  - Epigenetics in Alzheimer's disease: a focus on DNA modifications.
AB  - Epigenetic alterations have been associated with several human diseases including
      Alzheimer's disease (AD). AD is a complex neurodegenerative disease characterized
      by a progressive decline in cognitive functions, neuronal cell loss and by the
      presence of beta amyloid (Abeta) plaques and neurofibrillary tangles (NFTs) in
      the cortex. Mutations in specific genes have been identified but can only explain
      a small percentage of the AD cases. The origins of the sporadic cases of AD are
      still not known but there is evidence for a role of epigenetics in the etiology
      of the disease. In this review we focus on discussing the roles of DNA
      methylation and hydroxymethylation in the development and potential treatment of
      AD. We discuss papers showing that there are alterations in methylated cytosine
      (5mC) levels in AD and also highlight the potential role of hydroxylated
      methylcytosine (5hmC) in the epigenetic regulation of brain gene expression and
      perhaps in AD. We discuss the potential influence of environmental factors,
      working through epigenetic mechanisms, on increasing the risk of developing AD
      and their potential in treating this major neurodegenerative disorder.

PMID- 21902669
TI  - The mitochondrial cascade hypothesis for Parkinson's disease.
AB  - During the past decades, we have witnessed significant advances in our
      understanding of the molecular etiology of Parkinson's disease (PD). The
      unearthing of the causative genes for hereditary PD accelerated not only the
      studies of the molecular mechanisms underlying this pathology, but also set
      mitochondria at the center of PD pathology. In this review we revisit
      mitochondrial key role and propose a hypothesis for PD, that allows the
      unification of both sporadic and familial PD forms. In light of this we also
      discuss new promising disease-modified therapies.

PMID- 21902670
TI  - New insights into the mechanisms of mitochondrial preconditioning-triggered
      neuroprotection.
AB  - Mitochondria fulfill a number of essential cellular functions, being recognized
      that the strict regulation of the structure, function and turnover of these
      organelles is an immutable control node for the maintenance of neuronal integrity
      and homeostasis. Many lines of evidence posit that mitochondria constitute a
      convergence point of preconditioning - a paradigm that affords robust brain
      tolerance in the face of neurodegenerative insults. Indeed, it has been described
      that preconditioning activates an adaptive reprogramming of mitochondrial biology
      in response to a noxious stress-stimulus, which in turn will contribute to
      augment both mitochondrial and neuronal tolerance. Mitochondrial reactive species
      (ROS), mitochondrial ATP-sensitive potassium (mitoK(ATP)) channels and
      mitochondrial permeability transition pore have been identified as specific
      mitochondrial mediators and targets of the adaptive program underlying
      preconditioning. Recent studies further link mitochondrial biogenesis, dynamics
      and mitophagy to preconditioning, thereby representing novel mechanisms by which
      preconditioning may mediate brain tolerance. The present review summarizes the
      current views on how mitochondrial biology is linked to preconditioning-induced
      neuroprotection. A better understanding of the mitochondrial mechanisms
      underlying preconditioning will help in the development of novel therapeutic
      approaches with the primary goal of modulating mitochondria to enhance brain
      tolerance against neurodegenerative events.

PMID- 21902673
TI  - (-)-Epigallocatechin gallate suppresses adipocyte differentiation through the
      MEK/ERK and PI3K/Akt pathways.
AB  - EGCG [(-)-epigallocatechin gallate], tea catechin, is one of the compounds that
      has been reported to act against obesity and diabetes. To determine the effect of
      EGCG on adipocyte differentiation, we treated 3T3-L1 preadipocytes with different
      catechins. Oil Red O staining showed significantly reduced intracellular lipid
      accumulation, especially with EGCG. Cell cycle analysis showed that EGCG
      inhibited cell proliferation by disturbing the cell cycle during the clonal
      expansion of 3T3-L1. RT-PCR (real-time PCR) demonstrated that EGCG noticeably
      reduced mRNA expression of PPARgamma (peroxisome proliferator-activated receptor
      gamma), C/EBPalpha (CCAAT/enhancer-binding protein alpha) and FoxO1 (forkhead box
      class O1). EGCG also caused a significant decrease in the transcription of FoxO1 
      the forkhead transcription factor class O1 involved in adipocyte differentiation
      - via the PI3K (phosphoinositide 3-kinase)/Akt and MEK [MAPK (mitogen-activated
      protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] pathways.
      These results suggest that EGCG suppresses the clonal expansion of adipocytes by
      inactivating FoxO1 via insulin signalling and stress-dependent MAPK pathways.

PMID- 21902671
TI  - The mitochondrial dynamics of Alzheimer's disease and Parkinson's disease offer
      important opportunities for therapeutic intervention.
AB  - Mitochondrial dynamics play a crucial role in the pathobiology underlying
      Alzheimer's disease (AD) and Parkinson's disease (PD). Although a complete
      scientific understanding of these devastating conditions has yet to be realized,
      alterations in mitochondrial fission and fusion, and in the protein complexes
      that orchestrate mitochondrial fission and fusion, have been well established in
      AD- and PD-related neurodegeneration. Whether fission/fusion disruption in the
      brain is a causal agent in neuronal demise or a product of some other upstream
      disturbance is still a matter of debate; however, in both AD and PD, the
      potential for successful therapeutic amelioration of degeneration via
      mitochondrial protection is high. We here discuss the role of mitochondrial
      dynamics in AD and PD and assess the need for their therapeutic exploitation.

PMID- 21902674
TI  - Development of a disability scale for myotonic dystrophy type 1.
AB  - OBJECTIVES: Myotonic dystrophy type 1 (DM1) is a multisystem disorder. Many tests
      in the literature have evaluated single aspects of DM1 patients, mainly focusing
      on muscular impairment, without an overall quantification of the different
      disease-specific neurological features. We developed and validated a new
      functional scale for DM1 patients based on neuromuscular impairment (NI) and
      disability. MATERIALS AND METHODS: Thirty-three patients were tested in basal
      condition, 18 were re-evaluated after therapeutic intervention with mexiletine,
      and 13 at one year follow-up without treatment. The scale includes 21 ordinal
      items in four areas: neuropsychology, motricity, myotonia and daily life
      activities. We evaluated inter- and intra-observer reliability (intraclass
      correlation coefficient, ICC and Spearman correlations, respectively), internal
      consistency (Cronbach's alpha), external validity (Spearman correlations between
      each area and other clinical and objective measurements and scales), and
      sensitivity to clinical changes after treatment or at follow-up. RESULTS: Our
      analysis provided good results for inter-observer agreement (ICC = 0.72-0.97),
      intra-observer reliability, and internal consistency for all areas (Cronbach's
      alpha > 0.73). Total score and single area subscores were significantly
      correlated to objective measurements, disease duration and multisystem
      involvement. Finally, the scale was sensitive to clinical changes disclosing a
      significant improvement after treatment in the items assessing myotonia, and also
      to disease progression showing a significant worsening in all areas but myotonia
      in untreated patients. DISCUSSION: Our scale provides a new practical measure to
      evaluate NI and disability of DM1 patients. Further longitudinal studies are
      warranted to confirm its reliability in tracking disease progression and severity
      over a longer period of time.

PMID- 21902675
TI  - Craniotomy for brain metastases: a consecutive series of 316 patients.
AB  - OBJECTIVE: To assess the incidence of craniotomy for brain metastases, overall
      survival (OS), surgical mortality, and prognostic factors in a large,
      contemporary, consecutive series from a well-defined catchment area. MATERIAL AND
      METHODS: All patients >= 18 years who underwent craniotomies for intracranial
      metastases at Oslo University Hospital, Rikshospitalet and Ulleval, between 2005
      and June 30, 2009 were included (n = 316). Patients were identified from our
      prospectively collected database and a thorough review of all charts to validate
      the entered data was performed. RESULTS: The annual incidence of first-time
      craniotomy for a brain metastasis was 2.6/100,000 inhabitants. Patient age ranged
      from 25 to 87 years (median 64 years). The 30-day mortality rate was 3.8%. Median
      OS was 9.2 months. Recursive partitioning analysis was class I in 19.6%, class II
      in 59.2%, and class III in 21.2% with median OS of 16.2, 8.9, and 5.6 months,
      respectively (P < 0.001). Lung cancer and melanoma were associated with a higher
      risk (>1% per year) of developing brain metastases. Significant negative
      prognostic factors were age >= 65, a poor performance score, unstable
      extracranial disease, presence of extracranial metastases, multiplicity,
      metastasis in eloquent area, and no post-operative radiotherapy. CONCLUSIONS: In
      this population study, the annual incidence of a first-time craniotomy for a
      brain metastasis was 2.6/100,000, the 30-day mortality rate was 3.8%, and median
      OS was 9.2 months. The well-known prognostic factors were confirmed.

PMID- 21902676
TI  - A systematic review of the literature about competence and poor insight.
AB  - OBJECTIVE:   Formally, incompetence implies that a patient cannot meet the legal
      requirements for informed consent. Our aim was to review the scientific
      literature on the relationship between competence and insight in patients with
      psychiatric disorders, how competence and insight are connected in these patients
      and whether there are differences in competence and insight among patients with
      different disorders. METHOD:   A search in PubMed/Medline was performed. Articles
      were assessed on relevance criteria by two independent reviewers. Study design,
      population, variables, and outcomes were extracted. RESULTS:   Seven articles
      were included on studies of psychiatric inpatients and outpatients and of
      psychotic and non-psychotic patients. All studies used the MacArthur Competence
      Assessment Tool (MacCAT). All studies but one found a strong correlation between
      poor insight and incompetence. Psychotic patients with poor insight are very
      likely to be incompetent, and psychotic patients with adequate insight are
      generally competent. One well-executed study showed that in non-psychotic
      disorders, however, another relationship emerges; competence and insight do not
      completely overlap in these patients. CONCLUSION:   Most incompetent psychotic
      patients have poor insight, but non-psychotic patients with adequate insight were
      incompetent in a substantial number of cases. In sum: non-psychotic patients with
      adequate insight can be incompetent.

PMID- 21902678
TI  - Efficient genomewide selection of PCA-correlated tSNPs for genotype imputation.
AB  - The linkage disequilibrium structure of the human genome allows identification of
      small sets of single nucleotide polymorphisms (SNPs) (tSNPs) that efficiently
      represent dense sets of markers. This structure can be translated into linear
      algebraic terms as evidenced by the well documented principal components analysis
      (PCA)-based methods. Here we apply, for the first time, PCA-based methodology for
      efficient genomewide tSNP selection; and explore the linear algebraic structure
      of the human genome. Our algorithm divides the genome into contiguous
      nonoverlapping windows of high linear structure. Coupling this novel window
      definition with a PCA-based tSNP selection method, we analyze 2.5 million SNPs
      from the HapMap phase 2 dataset. We show that 10-25% of these SNPs suffice to
      predict the remaining genotypes with over 95% accuracy. A comparison with other
      popular methods in the ENCODE regions indicates significant genotyping savings.
      We evaluate the portability of genome-wide tSNPs across a diverse set of
      populations (HapMap phase 3 dataset). Interestingly, African populations are good
      reference populations for the rest of the world. Finally, we demonstrate the
      applicability of our approach in a real genome-wide disease association study.
      The chosen tSNP panels can be used toward genotype imputation using either a
      simple regression-based algorithm or more sophisticated genotype imputation
      methods.

PMID- 21902677
TI  - Maternal smokeless tobacco use in Alaska Native women and singleton infant birth
      size.
AB  - OBJECTIVE: To examine the effects of maternal prenatal smokeless tobacco use on
      infant birth size. DESIGN: A retrospective medical record review of 502 randomly
      selected deliveries. POPULATION AND SETTING: Singleton deliveries to Alaska
      Native women residing in a defined geographical region in western Alaska, 1997
      2005. METHODS: A regional medical center's electronic records were used to
      identify singleton deliveries. Data on maternal tobacco exposure and pregnancy
      outcomes were abstracted from medical records. Logistic models were used to
      estimate adjusted mean birthweight, length and head circumference for deliveries
      to women who used no tobacco (n=121), used smokeless tobacco (n=237) or smoked
      cigarettes (n=59). Differences in mean birthweight, length and head
      circumference, 95% confidence intervals and p-values were calculated using non
      users as the reference group. MAIN OUTCOME MEASURES: Infant birthweight, crown
      heel length and head circumference. RESULTS: After adjustment for gestational age
      and other potential confounders, the mean birthweight of infants of smokeless
      tobacco users was reduced by 78 g compared with that of infants of non-users
      (p=0.18) and by 331 g in infants of smokers (p<0.01). No association was found
      between maternal smokeless tobacco use and infant length or infant head
      circumference. CONCLUSIONS: We found a modest but non-significant reduction in
      the birthweight of infants of smokeless tobacco users compared with infants of
      tobacco non-users. Because smokeless tobacco contains many toxic compounds that
      could affect other pregnancy outcomes, results of this study should not be
      construed to mean that smokeless tobacco use is safe during pregnancy.

PMID- 21902672
TI  - Role and treatment of mitochondrial DNA-related mitochondrial dysfunction in
      sporadic neurodegenerative diseases.
AB  - Several sporadic neurodegenerative diseases display phenomena that directly or
      indirectly relate to mitochondrial function. Data suggesting altered
      mitochondrial function in these diseases could arise from mitochondrial DNA
      (mtDNA) are reviewed. Approaches for manipulating mitochondrial function and
      minimizing the downstream consequences of mitochondrial dysfunction are
      discussed.

PMID- 21902679
TI  - The role of genetic variability in the SLC6A4, BDNF and GABRA6 genes in anxiety
      related traits.
AB  - OBJECTIVE: The aims of this study were to test the individual association of the
      serotonin transporter gene (SLC6A4), the brain-derived neurotrophic factor gene
      (BDNF) and the GABA(A) alpha(6) receptor subunit gene (GABRA6) with anxiety
      related traits and to explore putative gene-gene interactions in a Spanish
      healthy sample. METHOD: A sample of 937 individuals from the general population
      completed the Temperament and Character Inventory questionnaire to explore Harm
      Avoidance (HA) dimension; a subsample of 553 individuals also filled in the Big
      Five Questionnaire to explore the Neuroticism dimension. The whole sample was
      genotyped for the 5-HTTLPR polymorphism (SLC6A4 gene), the Val66Met polymorphism
      (BDNF gene) and the T1521C polymorphism (GABRA6 gene). RESULTS: Homozygous
      individuals for the T allele of the T1512C polymorphism presented slightly higher
      scores for HA than C allele carriers (F = 2.96, P = 0.019). In addition, there
      was a significant gene-gene interaction on HA between the 5-HTTLPR and Val66Met
      polymorphisms (F = 3.4, P = 0.009). CONCLUSION: GABRA6 emerges as a candidate
      gene involved in the variability of HA. The effect of a significant gene-gene
      interaction between the SLC6A4 and BDNF genes on HA could explain part of the
      genetic basis underlying anxiety-related traits.

PMID- 21902680
TI  - Paediatric B-cell precursor acute lymphoblastic leukaemia with t(1;19)(q23;p13):
      clinical and cytogenetic characteristics of 47 cases from the Nordic countries
      treated according to NOPHO protocols.
AB  - The translocation t(1;19)(q23;p13)/der(19)t(1;19) is a risk stratifying
      aberration in childhood B-cell precursor acute lymphoblastic leukaemia (BCP ALL)
      in the Nordic countries. We have identified 47 children/adolescents with
      t(1;19)/der(19)t(1;19)-positive BCP ALL treated on two successive Nordic Society
      of Paediatric Haematology and Oncology (NOPHO) protocols between 1992 and 2007
      and have reviewed the clinical and cytogenetic characteristics of these cases,
      comprising 1.8% of all cases. The translocation was balanced in 15 cases (32%)
      and unbalanced in 29 cases (62%). The most common additional chromosome
      abnormalities were del(9p), i(9q), del(6q), and del(13q). The median age was 7
      years, the median white blood cell (WBC) count was 16 * 10(9)/l, and the
      female/male ratio was 1.2. The predicted event-free survival (EFS) at 5 and 10
      years was 0.79, whereas the predicted overall survival (OS) at 5 and 10 years was
      0.85 and 0.82, respectively. Nine patients had a bone marrow relapse after a
      median of 23 months; no patient had a central nervous system relapse. Additional
      cytogenetic abnormalities, age, gender, WBC count or whether the t(1;19) was
      balanced or unbalanced did not influence EFS or OS. Compared to cases with
      t(12,21) and high hyperdiploidy, EFS was similar, but overall survival was worse
      in patients with t(1;19)/der(19)t(1;19) (P = 0.004).

PMID- 21902681
TI  - KRN5500, a spicamycin derivative, exerts anti-myeloma effects through impairing
      both myeloma cells and osteoclasts.
AB  - The spicamycin analogue KRN5500 alters glycoprotein processing and induces damage
      in the endoplasmic reticulum (ER)-Golgi apparatus in cancer cells. In the present
      study, we explored the cytotoxic effects of KRN5500 on multiple myeloma (MM)
      cells and the bone marrow microenvironment with special reference to ER stress.
      Cell proliferation assay showed that KRN5500 induced G1 arrest and apoptosis in
      MM cells in a time- and dose-dependent manner. KRN5500 enhanced ER stress
      independently of caspase activation in MM cells. This cell death was observed
      even in the presence of bone marrow stroma cells or osteoclasts. Notably, KRN5500
      induced cell death also in osteoclasts. In vivo effects of KRN5500 were evaluated
      using two xenograft models established in severe combined immunodeficient (SCID)
      mice by either subcutaneous injection of RPMI 8226 cells or intra-bone injection
      of INA-6 cells to subcutaneously implanted rabbit bones (SCID-rab model). KRN5500
      significantly inhibited tumour growth in both animal models, and decreased the
      number of osteoclasts, which resulted in prevention of bone destruction in the
      SCID-rab model. These results suggest that KRN5500 exerts anti-MM effects through
      impairing both MM cells and osteoclasts. Therefore, this unique mechanism of
      KRN5500 might be a useful therapeutic option in patients with MM.

PMID- 21902683
TI  - MicroRNA expression profile in splenic marginal zone lymphoma.

PMID- 21902682
TI  - Fibroproliferative activity in patients with immune thrombocytopenia (ITP)
      treated with thrombopoietic agents.
AB  - This study assessed the grade of bone marrow (BM) fibrosis and its association
      with a seromarker for collagen-III formation and fibrosis-related cytokines in 25
      immune thrombocytopenia (ITP) patients treated with thrombopoietin receptor
      agonists (Tpo-RA) who had at least one BM biopsy. Assessment of 8 pre- and on
      treatment BM biopsies revealed statistically significant increases in reticulin.
      Reticulin in biopsies performed after a median of 1.4 years of treatment was
      graded: MF-0 in 3 (12%), MF-1 in 19 (76%), MF-2 in 2 (8%) and MF-3 in 1 (4%). No
      cytogenetic or flow-cytometric abnormalities were detected. Median pretreatment
      Procollagen III N-propeptide (PIIINP) (6.6 MUg/l) was significantly higher than
      on-treatment levels (5.6 MUg/l); both were higher than controls (3.4 MUg/l; P <
      0.001). PIIINP was negatively correlated with treatment duration (r = -0.49)
      suggesting a decelerated reticulin production over time. There was a trend
      towards an association between grade of reticulin and PIIINP. Transforming growth
      factor (GF)-beta and basic-Fibroblast GF were not different between patients and
      controls but Hepatocyte GF (HGF), an anti-fibrotic cytokine, was significantly
      elevated in patients. In conclusion, low-grade BM reticulin fibrosis is seen in
      most ITP patients on Tpo-RA. The novel findings of decreasing PIIINP and elevated
      HGF need further investigation to explore their significance in BM fibrogenesis.

PMID- 21902684
TI  - Impact of high-risk classification by FISH: an eastern cooperative oncology group
      (ECOG) study E4A03.
AB  - Lenalidomide with dexamethasone is a standard induction treatment regimen for
      newly diagnosed myeloma (although a Federal Drug Administration indication is
      still absent). In the context of the Phase 3 clinical trial E4A03 (lenalidomide
      plus dexamethasone in low or high doses), we queried whether a fluorescence in
      situ hybridization (FISH)-based genetic classification into high risk (HR) and
      standard risk (SR) multiple myeloma (MM) would remain clinically significant. Of
      445 E4A03 patients, 126 had FISH analysis; 21 were classified HR with t(4;14),
      t(14;16), or 17p13 deletions. Median survival follow-up approached 3 years.
      Patients with FISH data tended to be younger and healthier compared to the rest
      of the study population and, consequently, had superior overall survival (OS)
      results. Within the FISH cohort, shorter OS in the HR versus SR group (P = 0.004)
      corresponded to a hazard ratio of 3.48 [95% confidence interval: (1.42-8.53)], an
      effect also observed in multivariate analysis. Two-year OS rates were 91% for SR
      MM and 76% for HR MM. There was also evidence of interaction between risk status
      and treatment (P = 0.026). HR patients were less likely to attain good partial
      response (SR 46% and HR 30%, Odds Ratio = 2.0 [0.7-5.6]), but overall response
      rates were not different. FISH-based risk classification retained prognostic
      significance in patients receiving lenalidomide-based induction.

PMID- 21902685
TI  - Novel epitope evoking CD138 antigen-specific cytotoxic T lymphocytes targeting
      multiple myeloma and other plasma cell disorders.
AB  - The development of an immunotherapeutic strategy targeting CD138 antigen could
      potentially represent a new treatment option for multiple myeloma (MM). This
      study evaluated the immune function of CD138 peptide-specific cytotoxic T
      lymphocytes (CTL), generated ex vivo using an HLA-A2-specific CD138 epitope
      against MM cells. A novel immunogenic HLA-A2-specific CD138(260-268)  (GLVGLIFAV)
      peptide was identified from the full-length protein sequence of the CD138
      antigen, which induced CTL specific to primary CD138(+)  MM cells. The peptide
      induced CD138-CTL contained a high percentage of CD8(+)  activated/memory T cells
      with a low percentage of CD4(+)  T cell and naive CD8(+)  T cell subsets. The CTL
      displayed HLA-A2-restricted and CD138 antigen-specific cytotoxicity against MM
      cell lines. In addition, CD138-CTL demonstrated increased degranulation,
      proliferation and gamma-interferon secretion to HLA-A2(+) /CD138(+)  myeloma
      cells, but not HLA-A2(-) /CD138(+)  or HLA-A2(+) /CD138(-)  cells. The immune
      functional properties of the CD138-CTL were also demonstrated using primary HLA
      A2(+) /CD138(+)  cells isolated from myeloma patients. In conclusion, a novel
      immunogenic CD138(260-268)  (GLVGLIFAV) peptide can induce antigen-specific CTL,
      which might be useful for the treatment of MM patients with peptide-based vaccine
      or cellular immunotherapy strategies.

PMID- 21902687
TI  - Sickle cell nephropathy - a practical approach.
AB  - Despite its apparently simple molecular aetiology, sickle cell disease (SCD) has
      long been known to have a remarkably variable clinical course, with complications
      involving many organs including the kidneys. Whilst many affected individuals
      show no evidence of renal involvement into late adulthood, others develop renal
      dysfunction in childhood or early adult life with a significant proportion
      eventually requiring renal replacement therapy. This review explores the
      pathophysiology and clinical manifestations of sickle cell nephropathy (SCN) and
      discusses how each complication can be investigated, monitored and managed in the
      outpatient setting. We summarize current knowledge of genetic modulation of
      sickle-related renal dysfunction. We outline the evidence for various treatment
      options and discuss others for which little evidence currently exists.

PMID- 21902688
TI  - A glycoengineered anti-CD19 antibody with potent antibody-dependent cellular
      cytotoxicity activity in vitro and lymphoma growth inhibition in vivo.
AB  - Human cluster of differentiation (CD) antigen 19 is a B cell-specific surface
      antigen and an attractive target for therapeutic monoclonal antibody (mAb)
      approaches to treat malignancies of B cell origin. MEDI-551 is an affinity
      optimized and afucosylated CD19 mAb with enhanced antibody-dependent cellular
      cytotoxicity (ADCC). The results from in vitro ADCC assays with Natural Killer
      cells as effector cells, demonstrate that MEDI-551 is effective at lower mAb
      doses than rituximab with multiple cell lines as well as primary chronic
      lymphocytic leukaemia and acute lymphoblastic leukaemia samples. Targeting CD19
      with MEDI-551 was also effective in several severe combined immunodeficiency
      lymphoma models. Furthermore, the combination of MEDI-551 with rituximab resulted
      in prolonged suppression of tumour growth, demonstrating that therapeutic mAbs
      with overlapping effector function can be combined for greater tumour growth
      inhibition. Together, the data demonstrate that MEDI-551 has potent antitumour
      activity in preclinical models of B cell malignancies. The results also suggest
      that the combination of the ADCC-enhanced CD19 mAb with an anti-CD20 mAb could be
      a novel approach for the treatment of B cell lymphomas.

PMID- 21902686
TI  - Results of a randomized trial in children with Acute Myeloid Leukaemia: medical
      research council AML12 trial.
AB  - The Medical Research Council Acute Myeloid Leukaemia 12 (MRC AML12) trial
      (children) addressed the optimal anthracenedione/anthracycline in induction and
      the optimal number of courses of consolidation chemotherapy. 504 children (<16
      years) with AML were randomized between mitoxantrone/cytarabine/etoposide or
      daunorubicin/cytarabine/etoposide as induction chemotherapy and 270 entered a
      second randomization between a total of four or five courses of treatment. Ten
      year event-free (EFS) and overall survival (OS) was 54% and 63% respectively; the
      relapse rate was 35%. There was no difference in complete remission rate between
      the induction regimens, but there was a benefit for mitoxantrone with regard to
      relapse rate [32% vs. 39%; Hazard ratio (HR) 0.73; 95% confidence interval (CI)
      0.54, 1.00] and disease-free survival (DFS; 63% vs. 55%; HR 0.72; 95% CI 0.54,
      0.96). However, this did not translate into a better EFS or OS (HR 0.84; 95% CI
      0.63, 1.12). Results of the second randomization did not show a survival benefit
      for a fifth course of treatment (HR 1.01; 95% CI 0.63, 1.62), suggesting a
      ceiling of benefit for conventional chemotherapy and demonstrating the need for
      new agents. EFS was superior compared to the preceding trial AML10, partly due to
      fewer deaths in remission, highlighting the importance of supportive care.

PMID- 21902689
TI  - The vascular endothelium: still amazing us 30 years on.

PMID- 21902690
TI  - Bacteria and spontaneous experimental colitis: immunological changes.
AB  - BACKGROUND: Intestinal commensal flora seems to be a requisite for both human and
      experimental intestinal inflammation. Our aim was to assess the immunological
      changes in the colon of IL-10(-/-) mice depending on the environmental
      conditions. MATERIALS AND METHODS: Twelve wild-type (WT) and 24 IL-10(-/-) 4-week
      old mice were kept under specific pathogen-free (SPF) conditions for 4 weeks.
      Half of them were transferred to a conventional environment. Mice were sacrificed
      at 12 weeks of age, and the incidence and severity of colitis was assessed.
      Intraepithelial (IEL) and lamina propria (LPL) lymphocytes were assessed for
      phenotype and apoptosis by flow cytometry. Toll-like receptors 2 (TLR2) and TLR9
      expression was assessed by real-time PCR. Immunohistochemical analyses for cell
      apoptosis, TLR2 and MyD88 were also performed. RESULTS: IL-10(-/-) mice shifted
      to conventional conditions showed a greater incidence (66% vs. 50%) and severity
      of colitis than animals kept under SPF conditions (P = 0.009). The number of CD3+
      IEL was higher and their apoptosis rate lower in IL-10(-/-) than in their WT
      counterparts, regardless of the environment. In LPL, however, these differences
      were only observed in mice shifted to conventional conditions. TLR2 expression
      was significantly increased in SPF-housed IL-10(-/-) mice when compared to WT
      controls. Immunohistochemistry demonstrated the loss of TLR2 and MyD88 in damaged
      areas. CONCLUSIONS: In SPF conditions, IL-10 deficiency appears to be compensated
      by an increased epithelial TLR2 expression, thus resulting in a milder colonic
      damage. However, in conventional conditions, this compensatory mechanism would be
      exceeded inducing a more severe colonic damage with activation of LPL immune
      cells.

PMID- 21902691
TI  - Six-year prognosis of diabetic patients with coronary artery disease.
AB  - BACKGROUND: Diabetes is associated with increased cardiovascular mortality. The
      aim of our study was to determine the prognostic factors for mortality in
      patients with type 2 diabetes (T2DM) and coronary artery disease (CAD) who
      underwent coronary angiography and percutaneous coronary intervention. MATERIALS
      AND METHODS: Four hundred and forty-five consecutive T2DM patients with
      significant CAD (>= 75% stenosis) were included in our analysis. All patients
      underwent standard clinical examination, laboratory tests and transthoracic
      echocardiography with measurement of the left ventricular ejection fraction.
      Severity of CAD at the coronary angiography was evaluated using the Gensini
      score. Clinical follow-up was completed at 1, 3 and 6 years. RESULTS: During a
      mean follow-up of 73.3 +/- 22.1 months, 109 patients died (24.5%). Significant
      determinants of an increased risk of death at multivariable analysis were age (p
      < 0.001), serum creatinine (p = 0.001), peripheral vascular disease (p = 0.002),
      serum glucose (p = 0.004), serum fibrinogen (p = 0.011) and history of heart
      failure (HF, p = 0.011). When all the variables were entered as categorical
      variables, with continuous variables split at their median value, only history of
      HF, estimated glomerular filtration rate, serum glucose, serum fibrinogen (all p
      < 0.0001) and beta-blocker therapy at discharge (p = 0.027) were selected.
      CONCLUSIONS: Our study shows a relatively good prognosis of patients with T2DM.
      Comorbidities, namely HF and renal impairment, are main determinants of survival.

PMID- 21902692
TI  - Justification of 150 mg clopidogrel in patients with high on-clopidogrel platelet
      reactivity.
AB  - BACKGROUND: The GRAVITAS trial showed that 150 mg clopidogrel did not improve
      outcome in patients with high on-clopidogrel platelet reactivity (HPR) screened
      by the VerifyNow assay. We aimed to determine the impact of 150 mg clopidogrel in
      stable angina patients with HPR identified with conventional aggregometry (LTA).
      MATERIALS AND METHODS: Clopidogrel-naive stable angina patients before ad hoc
      percutaneous coronary intervention were recruited into a randomized, double
      blind, placebo-controlled trial (NCT00638326). Twelve to 24 h after the 600-mg
      loading dose of clopidogrel, ADP(5MUM)-stimulated maximal (AGGmax), late platelet
      aggregation (AGGlate) and vasodilator-stimulated phosphoprotein phosphorylation
      (VASP-PRI) were evaluated. Patients with HPR (AGGmax >= 34%) were randomly
      allocated to 75 or 150 mg clopidogrel after 4 weeks. After control platelet
      function measurements at day 28, 75 mg clopidogrel was administered to all
      patients until 1 year. RESULTS: The study was prematurely terminated at the stage
      of 200 enroled patients. Administration of 150 mg clopidogrel significantly
      reduced platelet aggregation (AGGmax: 45.0 +/- 6.8 vs. 33.8 +/- 15.1, P < 0.01;
      AGGlate: 27.1 +/- 14.7 vs. 13.8 +/- 18.0, P < 0.01) and VASP-PRI (57.5 +/- 15.2
      vs. 37.2 +/- 17.1; P < 0.01), while platelet reactivity remained unchanged in
      patients with HPR receiving 75 mg clopidogrel. The higher maintenance dose of
      clopidogrel was associated with a significant reduction in cardiovascular (CV)
      death and myocardial infarction (MI) (0% vs. 11.4%, P = 0.04) and in CV death, MI
      or target vessel revascularization (24.6% vs. 3.1%; P = 0.01) during 1 year.
      CONCLUSIONS: One-month administration of 150 mg maintenance dose of clopidogrel
      reduces platelet reactivity and might decrease the risk of thrombo-ischaemic
      complications in stable angina patients with HPR identified by LTA.

PMID- 21902693
TI  - Restoration of distorted colour microscopic images from transverse chromatic
      aberration of imperfect lenses.
AB  - An algorithm is presented for restoration of colour microscopic images with
      distortions from imperfect microscope lenses having transverse chromatic
      aberrations, resulting in a magnification that slightly varies with wavelengths
      or colours. The differential of each colour component image is computed as the
      difference between the component image and its slightly magnified version. The
      absolute values in the differential component images are generally higher at the
      edges where greater discontinuities occur. The two cross-correlation functions of
      the absolute differentials between red and green colours and between red and blue
      colours are then computed. The maximum in the two cross-correlation functions
      were sought, respectively, and the cross-correlation delays were then calculated.
      The two cross-correlation delays were used to determine dispersions and to
      realign the three colour components. Results of real microscopic images are
      provided. The restored image and the original are compared both visually and
      quantitatively in terms of the estimated entropies measured for the degree of
      concentrations using vector distributions.

PMID- 21902694
TI  - The forgotten science: reviving morphology.
AB  - Are modern science and clinicians forgetting or ignoring the importance of
      morphology and microscopy in studying disease and disease patterns? Here we
      ponder that current science research over-emphasizes the value of molecules and
      disease modelling, or rather under-estimate the usefulness of microscopy and
      morphology. We debate the usefulness of morphology in contemporary research and
      wonder whether our techniques are too old-fashioned or whether our field is seen
      as redundant.

PMID- 21902695
TI  - Functional diversification of the GALA type III effector family contributes to
      Ralstonia solanacearum adaptation on different plant hosts.
AB  - Type III effectors from phytopathogenic bacteria exhibit a high degree of
      functional redundancy, hampering the evaluation of their precise contribution to
      pathogenicity. This is illustrated by the GALA type III effectors from Ralstonia
      solanacearum, which have been shown to be collectively, but not individually,
      required for disease on Arabidopsis thaliana and tomato. We investigated
      evolution, redundancy and diversification of this family in order to understand
      the individual contribution of the GALA effectors to pathogenicity. From
      sequences available, we reconstructed GALA phylogeny and performed selection
      studies. We then focused on the GALAs from the reference strain GMI1000 to
      examine their ability to suppress plant defense responses and contribution to
      pathogenicity on three different host plants: A. thaliana, tomato (Lycopersicum
      esculentum) and eggplant (Solanum melongena). The GALA family is well conserved
      within R. solanacearum species. Patterns of selection detected on some GALA
      family members, together with experimental results, show that GALAs underwent
      functional diversification. We conclude that functional divergence of the GALA
      family likely accounts for its remarkable conservation during R. solanacearum
      evolution and could contribute to R. solanacearum's adaptation on several host
      plants.

PMID- 21902696
TI  - The spatial distribution of acid phosphatase activity in ectomycorrhizal tissues
      depends on soil fertility and morphotype, and relates to host plant phosphorus
      uptake.
AB  - Acid phosphatase (ACP) enzymes are involved in the mobilization of soil
      phosphorus (P) and polyphosphate accumulated in the fungal tissues of
      ectomycorrhizal roots, thereby influencing the amounts of P that are stored in
      the fungus and transferred to the host plant. This study evaluated the effects of
      ectomycorrhizal morphotype and soil fertility on ACP activity in the extraradical
      mycelium (ACP(myc)), the mantle (ACP(mantle)) and the Hartig net region
      (ACP(Hartig)) of ectomycorrhizal Nothofagus obliqua seedlings. ACP activity was
      quantified in vivo using enzyme-labelled fluorescence-97 (ELF-97) substrate,
      confocal laser microscopy and digital image processing routines. There was a
      significant effect of ectomycorrhizal morphotype on ACP(myc), ACP(mantle) and
      ACP(Hartig), while soil fertility had a significant effect on ACP(myc) and
      ACP(Hartig). The relative contribution of the mantle and the Hartig net region to
      the ACP activity on the ectomycorrhizal root was significantly affected by
      ectomycorrhizal morphotype and soil fertility. A positive correlation between
      ACP(Hartig) and the shoot P concentration was found, providing evidence that ACP
      activity at the fungus:root interface is involved in P transfer from the fungus
      to the host. It is concluded that the spatial distribution of ACP in
      ectomycorrhizas varies as a function of soil fertility and colonizing fungus.

PMID- 21902697
TI  - Comparative metabolomics of drought acclimation in model and forage legumes.
AB  - Water limitation has become a major concern for agriculture. Such constraints
      reinforce the urgent need to understand mechanisms by which plants cope with
      water deprivation. We used a non-targeted metabolomic approach to explore plastic
      systems responses to non-lethal drought in model and forage legume species of the
      Lotus genus. In the model legume Lotus. japonicus, increased water stress caused
      gradual increases of most of the soluble small molecules profiled, reflecting a
      global and progressive reprogramming of metabolic pathways. The comparative
      metabolomic approach between Lotus species revealed conserved and unique
      metabolic responses to drought stress. Importantly, only few drought-responsive
      metabolites were conserved among all species. Thus we highlight a potential
      impediment to translational approaches that aim to engineer traits linked to the
      accumulation of compatible solutes. Finally, a broad comparison of the metabolic
      changes elicited by drought and salt acclimation revealed partial conservation of
      these metabolic stress responses within each of the Lotus species, but only few
      salt- and drought-responsive metabolites were shared between all. The
      implications of these results are discussed with regard to the current insights
      into legume water stress physiology.

PMID- 21902698
TI  - Could rapid diameter changes be facilitated by a variable hydraulic conductance?
AB  - Adequate radial water transport between elastic bark tissue and xylem is crucial
      in trees, because it smoothens abrupt changes in xylem water potential, greatly
      reducing the likelihood of suffering dangerous levels of embolism. The radial
      hydraulic conductance involved is generally thought to be constant. Evidence
      collected about variable root and leaf hydraulic conductance led us to speculate
      that radial hydraulic conductance in stem/branches might also be variable and
      possibly modulated by putative aquaporins. We therefore correlated diameter
      changes in walnut (Juglans regia L.) with changes in water potential, altered by
      perfusion of twig samples with D-mannitol solutions having different osmotic
      potentials. Temperature and cycloheximide (CHX; a protein synthesis inhibitor)
      treatments were performed. The temperature response and diameter change
      inhibition found in CHX-treated twigs underpinned our hypothesis that radial
      hydraulic conductance is variable and likely mediated by a putative aquaporin
      abundance and/or activity. Our data demonstrate that radial water transport in
      stem/branches can take two routes in parallel: an apoplastic and a cell-to-cell
      route. The contribution of either route depends on the hydraulic demand and is
      closely linked to a boost of putative aquaporins, causing radial conductance to
      be variable. This variability should be considered when interpreting and
      modelling diameter changes.

PMID- 21902699
TI  - Intentional re-plantation of a vertically fractured tooth repaired with an
      adhesive resin.
AB  - AIM: To present the successful treatment of a vertically fractured tooth by
      intentional re-plantation after root canal treatment and repair with an adhesive
      resin. SUMMARY: Vertical root fracture is a challenging problem in respect of
      diagnosis and management options. In this case, a vertically fractured maxillary
      premolar was treated by intentional re-plantation after repairing it with 4
      Methacryloxyethyl trimellitate anhyride/methacrylate-tri-n-butyl borane (4
      META/MMA-TBB) resin cement. At the 36-month follow-up, the tooth was
      asymptomatic, radiographically sound with reduced deep periodontal pockets and
      vertical bone loss. KEY LEARNING POINTS: * Intentional replantation after
      repairing fractured fragments with an adhesive resin extraorally is a treatment
      option. * Long-term follow-up is necessary to evaluate the outcome of this
      technique.

PMID- 21902700
TI  - Anti-adhesive and pro-apoptotic effects of 2-hydroxyethyl methacrylate on human
      gingival fibroblasts co-cultured with Streptococcus mitis strains.
AB  - AIM: To evaluate and observe the cellular reactions that occur during the
      interaction/integration between 2-hydroxyethyl methacrylate/host tissue/microbial
      environment, in a co-culture of human gingival fibroblasts (HGF) and
      Streptococcus mitis strains. METHODOLOGY: Streptococcus mitis were cultured with
      strains in the presence of 3 mmol L(-1) HEMA for 48 h and 72 h. Cytotoxicity was
      evaluated by the trypan blue dye exclusion test. Apoptosis was evaluated by TUNEL
      analysis. Adhesion was evaluated by immunofluorescence and western blot analyses.
      Quantitative analyses of the results were acquired by Qwin Plus 3.5 and
      QuantityOne I-D analysis software, respectively. The statistical significance of
      the results was evaluated using t-tests and linear regression tests. RESULTS: The
      trypan blue dye test revealed 47.3% and 46.5% of dead fibroblasts after 48 and 72
      h HEMA treatment, respectively, while bacterial viability was not influenced by
      the presence of HEMA and fibroblasts. The expression of pro-collagen I, involved
      in fibroblast adhesion, in untreated samples ranged from 12.49% to 6.91% of the
      positive area after 48 and 72 h, respectively, dropping to below 2% of the
      positive area in the other experimental conditions. Unlike the trypan blue test,
      co-cultured samples treated with HEMA showed 20% and 25% versus 17% and 21%
      (after 48 and 72 h, respectively) of apoptotic cells. CONCLUSIONS: The evidence
      for HEMA toxicity and anti-adhesive effects against eukaryotic cells was reduced
      in the presence of bacteria, suggesting that dental resins should be well
      polymerized to avoid the spread of toxic monomers within the mouth.

PMID- 21902701
TI  - The effect of calcium hydroxide on the steroid component of Ledermix and
      Odontopaste.
AB  - AIM: To investigate the chemical interaction of calcium hydroxide with the
      corticosteroid triamcinolone acetonide in Ledermix Paste and in Odontopaste, a
      new steroid/antibiotic paste. METHODOLOGY: Validated methods were developed to
      analyse the interaction of calcium hydroxide in two forms, Pulpdent Paste and
      calcium hydroxide powder, with triamcinolone acetonide within Odontopaste and
      Ledermix Paste. High-performance liquid chromatography (HPLC) was used to analyse
      the mixed samples of the pastes and calcium hydroxide. The concentration of
      triamcinolone acetonide within the pastes was determined over 0, 2, 6, 24 and 72
      h time-points. All tests with the HPLC involved the testing of the standard with
      triplicate injections alongside the samples. All samples were tested in duplicate
      with each injected twice; therefore, four tests were performed for each
      investigation. Linearity, precision and specificity of the testing procedures and
      apparatus were validated. Descriptive statistics are provided. RESULTS: In both
      pastes, there was a marked rapid destruction of the triamcinolone acetonide
      steroid upon mixing with calcium hydroxide. Odontopaste suffered a lower rate of
      destruction of the triamcinolone acetonide component than Ledermix Paste, but
      both pastes showed very similar degrees of steroid destruction after 72 h. When
      using calcium hydroxide powder with Ledermix Paste, the triamcinolone was
      destroyed entirely and immediately. CONCLUSION: The addition of calcium hydroxide
      to Odontopaste or Ledermix Paste results in the rapid destruction of the steroid.

PMID- 21902702
TI  - A multiparametric assay to compare the cytotoxicity of endodontic sealers with
      primary human osteoblasts.
AB  - AIM:   To compare the cytotoxicity of four endodontic sealers (Sealapex, Pulp
      Canal Sealer EWT, Real Seal and MTA Fillapex) either 1 or 7 days after mixing,
      when assessed through a multiparametric analysis employing human primary cells
      closely related to periapical tissues. METHODOLOGY:   Extracts of each sealer
      were prepared following 24-h exposure to culture media, at either 24 h or 7 days
      after mixing. Primary human osteoblasts were exposed to extracts for 24 h, at 37 
      degrees C with 5% CO(2) , and cell viability was evaluated by a multiparametric
      assay assessing sequentially, on the same cells, mitochondrial activity (XTT),
      membrane integrity (neutral red test) and total cell density (crystal violet dye
      exclusion test). Results from each test and experimental time were compared by 2
      way analysis of variance (anova). RESULTS:   All endodontic sealers had strong
      cytotoxicity 24 h after mixing, according to all parameters evaluated. At a
      longer setting period (7 days), viability for Sealapex was significantly
      increased (P < 0.05) and Pulp Canal Sealer achieved levels of cytocompatibility
      similar to the control group. The anova indicated a general correlation between
      the cytotoxicity of the materials and the time after mixing, with some level of
      dependence on the cell viability assay employed. CONCLUSIONS:   All materials had
      high cytotoxic levels for human primary cells, mostly on a time-dependent basis,
      as shown by three different cell viability tests.

PMID- 21902703
TI  - Effect of white mineral trioxide aggregate compared with biomimetic carbonated
      apatite on dentine bridge formation and inflammatory response in a dental pulp
      model.
AB  - AIM:   To evaluate the effects of apatite precipitation on the biocompatibility
      and hard tissue induction properties of white mineral trioxide aggregate (WMTA)
      in a dental pulp model. METHODOLOGY:   Pulp exposures were created on the axial
      walls of 32 sound canine teeth of eight dogs. Four additional sound teeth served
      as controls. The pulps were capped either with WMTA or apatite derivatives
      [biomimetic carbonated apatite (BCAp)] in the interaction of WMTA with a
      synthetic tissue fluid and restored with zinc oxide-eugenol cement. After 7 and
      70 days, the animals were killed, and the histological specimens taken from the
      teeth were stained with haematoxylin and eosin for histomorphological evaluation.
      The Brown and Brenn technique was employed to stain bacteria. The data were
      subjected to nonparametric Kruskall-Wallis analysis and Mann-Whitney U_tests.
      RESULTS:   Biomimetic carbonated apatite did not induce hard tissue bridge
      formation. WMTA performed significantly better than BCAp in this respect at both
      periods (P < 0.05). BCAp was associated with a significantly greater inflammatory
      response as compared with WMTA after 7 days (P < 0.05). Both materials were
      associated with similar reactions after 70 days (P >0.05). CONCLUSIONS:   White
      mineral trioxide aggregate induced hard tissue formation via a mechanism other
      than that postulated via apatite formation.

PMID- 21902705
TI  - Alteration in the inherent metallic and surface properties of nickel-titanium
      root canal instruments to enhance performance, durability and safety: a focused
      review.
AB  - The expanded use of nickel-titanium (NiTi) rotary instruments in root canal
      procedures has led to the development of a wide variety of shapes, designs and
      applications. Root canal anatomy has not changed, however, and the same
      challenges exist in both initial treatment and the revision of unacceptable
      treatment. These challenges include application with high levels of achievement
      and low to no levels of adverse effects, such as instrument fracture, root canal
      wall ledging, dentine wall perforation and so forth. To that end, many
      manufacturers have been seeking ways to alter the presently available and wide
      range of root canal instrument designs, with a focus on altering the surface of
      the alloy or altering the alloy microstructure with post-machining or post
      twisting heat treatment. This focused review will address the impact that these
      modifications have had on instrument flexibility, resistance to cyclic fatigue
      and cutting efficiency.

PMID- 21902704
TI  - Effects of three oral analgesics on postoperative pain following root canal
      preparation: a controlled clinical trial.
AB  - AIM:   To compare the effects of single doses of three oral medications on
      postoperative pain following instrumentation of root canals in teeth with
      irreversible pulpitis. METHODOLOGY:   In this double-blind clinical trial, 100
      patients who had anterior or premolar teeth with irreversible pulpitis without
      any signs and symptoms of acute or chronic apical periodontitis and moderate to
      severe pain were divided by balanced block random allocation into four groups of
      25 each, a control group receiving a placebo medication, and three experimental
      groups receiving a single dose of either Tramadol (100 mg), Novafen (325 mg of
      paracetamol, 200 mg ibuprofen and 40 mg caffeine anhydrous) or Naproxen (500 mg)
      immediately after the first appointment where the pulp was removed, and the
      canals were fully prepared. The intensity of pain was scored based on 10-point
      VAS before and after treatment for up to 24 h postoperatively. Data were
      submitted to repeated analysis of variance. RESULTS:   At the 6, 12 and 24 h
      postoperative intervals after drug administration, the intensity of pain was
      significantly lower in the experimental groups than in the placebo group (P <
      0.01). Tramadol was significantly less effective (P < 0.05) than Naproxen, and
      Novafen that were similar to each other (P > 0.05). CONCLUSION:   A single oral
      dose of Naproxen, Novafen and Tramadol taken immediately after treatment reduced
      postoperative pain following pulpectomy and root canal preparation of teeth with
      irreversible pulpitis.

PMID- 21902706
TI  - The prevalence of dentine hypersensitivity in Chinese adults.
AB  - Dentine hypersensitivity is a common oral problem. This study investigated the
      prevalence of dentine hypersensitivity in the adult population of Shanghai,
      China. A multi-stage, stratified, random sampling method was used to investigate
      the study population. A total of 2120 subjects were examined at 10 investigation
      points in Shanghai City. Subjects were divided into age groups (10 years per age
      group) and included the same number of male and female subjects in each group.
      Participants completed a dentine hypersensitivity questionnaire and underwent
      clinical examination. The diagnosis of dentine hypersensitivity was confirmed
      clinically as a sharp well-localised pain in response to administration of a
      blast of cold air from a triple syringe. Gingival recession of sensitive teeth
      was measured by a Williams periodontal probe. Among 2120 participants, 723 were
      diagnosed as having dentine hypersensitivity, indicating a prevalence of 34.1%.
      The male to female ratio of dentine hypersensitivity was 1:1.5. The prevalence of
      dentine hypersensitivity was highest in the 40- to 49-year age group at 43.9%.
      The number of teeth with dentine hypersensitivity was 3.2 per patient. Dentine
      hypersensitivity occurred predominantly in the premolars (49.6%), followed by the
      anterior teeth (30.5%). A total of 84.3% of dentine hypersensitive patients had
      gingival recession. The prevalence of dentine hypersensitivity in Shanghai adults
      was 34.1%, indicating that it is a common condition. Therefore, public education
      about the condition and effective treatment of dentine hypersensitivity are
      required.

PMID- 21902707
TI  - Periapical and endodontic status of permanent teeth in patients with
      hypophosphatemic rickets.
AB  - Hypophosphatemic rickets (HR) is a rare hereditary disease in which dental
      problems in terms of spontaneous periapical infections are frequently reported.
      Most previous reports have been based on a small number of HR patients and have
      been published before the disease could be confirmed genetically. The aim of the
      present study was to describe the periapical and endodontic status of permanent
      teeth in patients with genetically and/or biochemically confirmed HR. The
      patients were recruited from a medical study on HR patients. The patients
      underwent a dental examination including a digital panoramic radiograph, which
      was scored for endodontically affected teeth (i.e. teeth with periapical
      radiolucencies and/or endodontically treated teeth). A total of 52 patients (age
      range: 5.7-74.5 years; 17 males and 35 females) were included. HR patients were
      characterised by a high number of endodontically affected teeth (mean: 4.2; s.d.:
      5.0). The number of affected teeth rose significantly with age (P < 0.01), and no
      statistically significant gender difference was found. The relative distribution
      of endodontically affected teeth in the three tooth groups (incisors and canines,
      premolars, and molars) varied according to age. In the youngest age group, only
      incisors and canines were affected, while the relative proportion of affected
      premolars and molars increased with age. Endodontically affected teeth are common
      in HR patients, and the number of affected teeth increased significantly with
      age. Hence, the need for endodontic treatment among HR patients is comprehensive.

PMID- 21902708
TI  - Changes in molar position associated with missing opposed and/or adjacent tooth:
      a 12-year study in women.
AB  - The aim of this study was to radiographically analyse long-term changes in (i)
      overeruption of unopposed molars and (ii) tipping of molars with a mesial
      edentulous space, and whether there is an interaction between the two events. A
      further aim was to analyse if loss of alveolar bone height might influence
      overeruption and tipping. The sample consisted of panoramic radiographs taken at
      an interval of 12 years of 292 subjects from a prospective population study of
      women. The panoramic radiographs were scanned and analysed. Changes in tipping,
      overeruption and alveolar bone height of molars and control teeth were measured.
      The results showed that unopposed molars were more commonly found in the upper
      jaw and that unopposed molars showed 4.9 times higher risk of overeruption of >=2
      mm (95% CI 1.5-15.3) than opposed molars during the 12-year observation period.
      The average overeruption for the unopposed molars was 4.5% (s.d. 7.6), which
      corresponds to approximately 0.9 mm. The degree of overeruption increased with
      decreased bone support. Molars with a mesial edentulous space were most prevalent
      in the lower jaw, but neither an edentulous space nor alveolar bone level/bone
      level change were found to have a significant effect on tipping of the molars.
      The average mesial tipping was 0.8 degrees  (s.d. 5.6). In conclusion, unopposed
      molars showed a significantly increased risk for overeruption. Molars facing a
      mesial edentulous space showed a low risk for mesial tipping, but a significant
      interaction between overeruption and tipping was identified.

PMID- 21902709
TI  - Perceived environmental restrictions for the participation of children with mild
      developmental disabilities.
AB  - AIM: In light of the International Classification of Functioning, and Health
      (ICF) model, to assess whether parents of children with mild developmental
      disabilities perceived various environmental factors as barriers to their child's
      participation, and whether these factors have a unique contribution to the total
      explained variance of participation, beyond personal factors. METHODS: Seventy
      nine kindergarten children (mean age 5.20 +/- 0.52 years old) with mild
      developmental disabilities and their parents participated in the study. Three
      questionnaires measuring the child's participation, performance skills and
      environmental factors were completed by the parents. RESULTS: Parents perceived
      environmental factors as slightly restricting to their child's participation.
      Associations were found between home and education factors and the dimensions of
      child participation - independence, enjoyment and parental satisfaction. Although
      parents perceived human environmental factors as more restricting than physical
      factors at home, regression analysis revealed that the latter was found to affect
      the child participation dimension of independence beyond the contribution of
      personal factors. INTERPRETATION: These findings are the first, to our knowledge,
      to support the contribution of environmental factors to the participation of
      young children with mild developmental disabilities. The results show that
      environmental factors have significant slight contribution to child's
      independence in participation beyond other predictors (i.e. personal factors).
      Therefore, it is recommended to include environmental restrictions measurement in
      the child evaluation process to facilitate effective intervention programs.

PMID- 21902710
TI  - The influence of the absence of fathers and the timing of separation on anxiety
      and self-esteem of adolescents: a cross-sectional survey.
AB  - BACKGROUND: Many rural children in China have been experiencing life without
      fathers since the 1990s, when their fathers left the rural areas for the urban
      areas to find a job that would allow them to continue to support their family.
      However, to date, knowledge and understanding of the effects of the absence of
      fathers and timing of separation on the mental health of adolescents are limited.
      METHODS: A total of 2233 students, ranging in age from 11 to 23 years, from five
      provinces of China, including 1024 adolescents who experienced the absence of
      their fathers, were recruited for this study. The data were collected using State
      Trait Anxiety Inventory and Rosenberg Self-Esteem Scale, which were self-report
      questionnaires. RESULTS: Findings from a structured questionnaire showed that the
      subjects who experienced life without fathers have increased state-anxiety (t=
      5.80, P < 0.001) and lower self-esteem (t= 39.54, P < 0.001) when compared with
      other subjects, and the above results could be influenced by gender and grade. A
      limited effect of the timing of separation was found on the mental health of
      students whose fathers were absent. A significant timing group effect existed for
      state-anxiety scores [F(3,992) = 2.26, P= 0.05], and post test also revealed that
      the self-esteem of female scores in the 0-2 timing group was higher than other
      timing group's [F(3,992) = 4.58, P= 0.004]. CONCLUSION: The influence of the
      absence of fathers on the anxiety and self-esteem of adolescents seems to be more
      serious than our expectation, and the influence will be different according to
      the timing of father absence.

PMID- 21902712
TI  - Living-related donation: a challenge to adolescent transplant recipients who
      transit from parental care to self-managed care.

PMID- 21902711
TI  - Two sides of the mirror: parents' and service providers' view on the family
      centredness of care for children with cerebral palsy.
AB  - BACKGROUND: In order to best meet the needs of both families and their children
      with cerebral palsy, many rehabilitation service providers have adopted a family
      centred service (FCS) approach. In FCS parents are seen as experts on their
      child's needs, and the family and professionals collaborate in the rehabilitation
      process. However, parents and service providers might look at FCS from different
      points of view, i.e. look into the mirror from two different sides. The objective
      of this study was to explore the degree to which parents experience the service
      as being family-centred and to which extent the service providers experience
      their service provision as family-centred. METHODS: A translated version of The
      Measure of Processes of Care 20 (MPOC-20) questionnaire was used to evaluate
      parents' experience of FCS, and a Measures of Processes of Care for Service
      Providers (MPOC-SP) questionnaire was used to evaluate the FCS provided by
      professionals. Parents visiting two university hospital neuropediatric wards (n=
      67) during a 2-month period and who were willing to participate received the
      questionnaire. Also the service providers working on the same wards (n= 49) were
      invited to participate. RESULTS: A total of 53 families and 29 service providers
      completed the questionnaires. Both parents and professionals generally rated the
      FCS positively. General information was rated lowest and respectful treatment the
      highest by both parents and professionals. The results revealed that written
      information about the child's condition, the possibility to choose when to
      receive information, and contact with other families in the same situation are
      areas in need of improvement. CONCLUSIONS: The possibility to regularly evaluate
      services both from the families' and the professionals' perspectives should be
      part of quality development. Providing general information is a challenge for all
      service providers. The MPOC questionnaires can be used to highlight important
      areas of improvement in FCS.

PMID- 21902713
TI  - Stimulus-dependent release of tissue-regenerating factors by equine platelets.
AB  - REASONS FOR PERFORMING THE STUDY: Platelet-rich plasma (PRP) is increasingly used
      for treatment of orthopaedic injuries. However, the effects of different stimuli
      on the release pattern of regenerative and proinflammatory factors from equine
      platelets are largely unknown and an optimal treatment protocol remains to be
      established. OBJECTIVES: The aim of this study was to identify a stimulus that
      enhanced release of histopromotive factors (platelet-derived growth factor BB
      [PDGF] and transforming growth factor 1beta[TGF]) without causing concurrent
      release of a proinflammatory mediator (CCL5). METHODS: Washed platelets were
      prepared from 6 healthy ponies and release of growth factors and CCL5 measured
      using commercially available ELISAs for human proteins following incubation with
      or without thrombin, chitosan or equine recombinant tumour necrosis factor
      (erTNF) over 24 h and subsequently over 96 h. Additionally, noncoagulated samples
      were analysed. RESULTS: Regardless of whether a stimulus was present or what
      stimulus was used, PDGF and TGF release was maximal by 0.5-1 h when clot
      formation took place and very little release was observed after 24 h. Growth
      factor release was minimal in noncoagulated samples. In contrast, CCL5 release
      was not associated with coagulation and appeared to persist for much longer. High
      concentrations of erTNF caused significantly greater release of CCL5 at 6 h than
      any other stimulus tested. CONCLUSIONS: Growth factor release from equine
      platelets is dependent on coagulation but independent of the initiating stimulus,
      and is accompanied by more sustained release of proinflammatory mediators.
      POTENTIAL RELEVANCE: Supernatants collected from coagulated platelets could be an
      alternative treatment to PRP.

PMID- 21902716
TI  - Going back to the land in the age of entitlement.

PMID- 21902717
TI  - Managing for caribou and ecological integrity: reply to Serrouya and Wittmer
      2010.

PMID- 21902718
TI  - Extirpation of macroalgae (Sargassum spp.) on the subtropical east Australian
      coast.
AB  - Populations of large brown algae of the Laminariales and Fucales (Phaeophyta)
      have declined or been extirpated from many locations on temperate coasts
      worldwide. We conducted field surveys and a literature review, and examined
      herbarium specimens, through which we discovered previously unreported
      extirpations of large brown algal species from a tropical and subtropical
      coastline. Sargassum amaliae, S. aquifolium, S. carpophyllum, S. polycystum, and
      S. spinifex were common habitat-forming macroalgae that supported diverse
      assemblages of invertebrates and smaller algae before urbanization began in 1970
      along the 45-km length of Sunshine Coast in Queensland, Australia. Causes of
      these extirpations are not known, but are consistent with losses of other large
      brown algal species from coastal areas undergoing urbanization or eutrophication.
      Sargassum spp. do not have the characteristics thought to protect marine species
      from extinction (large geographical ranges, occurrence on many different
      substrata, long-distance dispersal). Some local Sargassum spp. are endemic to
      eastern Australia. Abundance of Sargassum is limited by suitable substrata on the
      sandy southern Queensland coast (370 km). These substrata are 12 rocky headlands
      separated by long (5-105 km) sandy beaches. Most multicellular propagules (the
      only motile stage in Sargassum) settle within 1-3 m of parental thalli, which
      restricts long-distance dispersal needed to maintain connectivity among
      populations and to recolonize areas of the headlands from which populations have
      been extirpated. Local Sargassum spp. could be categorized as data deficient by
      the International Union for Conservation of Nature (IUCN), but the IUCN
      vulnerable category is more accurate given extirpations, limited habitat, and the
      lack of connectivity among populations.

PMID- 21902719
TI  - Environmental refuge from disease-driven amphibian extinction.
AB  - Species that are tolerant of broad environmental gradients may be less vulnerable
      to epizootic outbreaks of disease. Chytridriomycosis, caused by the fungus
      Batrachochytrium dendrobatidis, has been linked to extirpations and extinctions
      of amphibian species in many regions. The pathogen thrives in cool, moist
      environments, and high amphibian mortality rates have commonly occurred during
      chytridiomycosis outbreaks in amphibian populations in high-elevation tropical
      rainforests. In Australia several high-elevation species, including the armored
      mist frog (Litoria lorica), which is designated as critically endangered by the
      International Union for the Conservation of Nature (IUCN), were believed to have
      gone extinct during chytridiomycosis outbreaks in the 1980s and early 1990s.
      Species with greater elevational ranges disappeared from higher elevations, but
      remained common in the lowlands. In June 2008, we surveyed a stream in a high
      elevation dry sclerophyll forest and discovered a previously unknown population
      of L. lorica and a population of the waterfall frog (Litoria nannotis). We
      conducted 6 additional surveys in June 2008, September 2008, March 2009, and
      August 2009. Prevalences of B. dendrobatidis infection (number infected per total
      sampled) were consistently high in frogs (mean 82.5%, minimum 69%) of both
      species and in tadpoles (100%) during both winter (starting July) and summer
      (starting February). However, no individuals of either species showed clinical
      signs of disease, and they remained abundant (3.25 - 8.75 individuals of L.
      lorica and 6.5-12.5 individuals of L. nannotis found/person/100 m over 13
      months). The high-elevation dry sclerophyll site had little canopy cover, low
      annual precipitation, and a more defined dry season than a nearby rainforest
      site, where L. nannotis was more negatively affected by chytridiomycosis. We
      hypothesize this lack of canopy cover allowed the rocks on which frogs perched to
      warm up, thereby slowing growth and reproduction of the pathogen on the hosts. In
      addition, we suggest surveys for apparently extinct or rare species should not be
      limited to core environments.

PMID- 21902720
TI  - A spatially explicit estimate of avoided forest loss.
AB  - With the potential expansion of forest conservation programs spurred by climate
      change agreements, there is a need to measure the extent to which such programs
      achieve their intended results. Conventional methods for evaluating conservation
      impact tend to be biased because they do not compare like areas or account for
      spatial relations. We assessed the effect of a conservation initiative that
      combined designation of protected areas with payments for environmental services
      to conserve over wintering habitat for the monarch butterfly (Danaus plexippus)
      in Mexico. To do so, we used a spatial-matching estimator that matches covariates
      among polygons and their neighbors. We measured avoided forest loss (avoided
      disturbance and deforestation) by comparing forest cover on protected and
      unprotected lands that were similar in terms of accessibility, governance, and
      forest type. Whereas conventional estimates of avoided forest loss suggest that
      conservation initiatives did not protect forest cover, we found evidence that the
      conservation measures are preserving forest cover. We found that the conservation
      measures protected between 200 ha and 710 ha (3-16%) of forest that is high
      quality habitat for monarch butterflies, but had a smaller effect on total forest
      cover, preserving between 0 ha and 200 ha (0-2.5%) of forest with canopy cover
      >70%. We suggest that future estimates of avoided forest loss be analyzed
      spatially to account for how forest loss occurs across the landscape. Given the
      forthcoming demand from donors and carbon financiers for estimates of avoided
      forest loss, we anticipate our methods and results will contribute to future
      studies that estimate the outcome of conservation efforts.

PMID- 21902722
TI  - Oral squamous cell carcinoma grading systems--analysis of the best survival
      predictor.
AB  - BACKGROUND: The TNM system has been used for decades in an attempt to predict
      clinical behavior and appropriate therapy for oral squamous cell carcinomas.
      Histopathologic classifications can be useful as an additional predictive tool.
      The purpose of this study was to apply four grading systems (Multiparameter
      Grading System, Malignancy Grading of the Deep Invasive Margins, World Health
      Organization grading system, and Histologic Risk Assessment) to oral squamous
      cell carncinomas and evaluate each system based on clinicopathologic parameters
      and patient survival. METHODS: The files of 53 patients diagnosed with primary
      oral squamous cell carcinoma at the Brazilian National Cancer Institute were
      evaluated. All hematoxylin and eosin-stained slides were reviewed to confirm the
      original diagnosis and to determine histopathologic grading. Clinicopathologic
      information was obtained from medical records and tumor registries. Statistical
      analysis was performed using Fisher's exact test or the chi-square test, the
      Kaplan-Meier method, and the log-rank test. RESULTS: The Multiparameter Grading
      System was statistically associated with pathologic staging (P = 0.02) and lymph
      node involvement (P = 0.0009). Differences in overall 5-year survival were
      significant for Histologic Risk Assessment (P = 0.015), pathologic staging (P =
      0.001), lymph node status (P < 0.0001), and recurrence (P = 0.0001). Differences
      in cancer-specific 5-year survival were significant for Histologic Risk
      Assessment (P = 0.029), pathologic staging (P = 0.002), lymph node involvement (P
      < 0.0001), and recurrence (P < 0.0001). Poorly differentiated tumors were
      associated with the worst disease-free survival (P = 0.031) and recurrence (P =
      0.043). CONCLUSION: Of the grading systems evaluated, Histologic Risk Assessment
      demonstrated the best results for survival prediction in oral squamous cell
      carcinoma.

PMID- 21902723
TI  - Long-term administration of prazosin improves bladder storage function: results
      from a study in spontaneously hypertensive rats.
AB  - OBJECTIVES: To investigate the effects of long-term administration of the
      alpha(1) -adrenoceptor antagonist prazosin on afferent inputs from the lower
      urinary tract (LUT). METHODS: Twenty female spontaneously hypertensive rats (SHR)
      were randomized to receive a 4-week course of prazosin (0.12 mg/kg per day) or
      vehicle; 10 female Wistar-Kyoto (WKY) rats were given vehicle. Prazosin or
      vehicle was administered via an osmotic pump. The effect of prazosin on
      urodynamic parameters was determined by continuous cystometry in conscious
      animals. After cystometry, rats were killed and c-fos expression in the dorsal
      horn of the L6 spinal cord was measured by immunohistochemistry. RESULTS: The
      bladder contraction interval was significantly shorter in untreated SHR compared
      with WKY rats (2.36 +/- 0 vs 4.27 +/- 0.12 min, respectively; P < 0.05) and
      cystometric capacity was decreased significantly in SHR compared with WKY rats.
      L6 spinal cord c-Fos expression was also significantly greater in SHR than WKY
      rats. The administration of prazosin significantly increased the micturition
      interval (4.07 +/- 0.58 min; P < 0.05) and bladder capacity, but it did not
      affect micturition pressure. In SHR, the number of c-Fos-positive neurons was
      significantly lower following the administration of prazosin compared with
      vehicle. CONCLUSIONS: Increased afferent input from the LUT may induce an
      increase in urinary frequency in SHR. Furthermore, long-term administration of
      prazosin can exert inhibitory effects on afferent pathways from the LUT during
      the storage phase. Reductions of afferent input can result in increased bladder
      capacity and increased micturition interval.

PMID- 21902724
TI  - Inhibitory effect of sodium hypochlorite and chlorhexidine digluconate in
      clinical isolates of Sporothrix schenckii.
AB  - The susceptibility of Sporothrix schenckii isolates from clinical cases of
      canine, feline and human sporotrichosis, and from the environment, was evaluated
      with 4% sodium hypochlorite and 6.6% chlorhexidine digluconate using the broth
      microdilution, agar diffusion and direct exposure techniques. The minimal
      inhibitory concentration was smaller than 0.8% for chlorhexidine digluconate and
      between 8% and 4% for sodium hypochlorite. Inhibition zones were not found in
      agar diffusion for sodium hypochlorite, and zones averaging 1.9 mm were found for
      chlorhexidine digluconate. In the direct exposure test, sodium hypochlorite
      demonstrated best performance at 20 min of contact, as chlorhexidine digluconate
      presented little antimicrobial activity.

PMID- 21902725
TI  - The risk of cytomegalovirus recurrence after kidney transplantation.
AB  - Recurrent cytomegalovirus (CMV) infections commonly occur after kidney
      transplantation. We studied the impact of secondary prophylaxis and other factors
      on the risk of CMV recurrence. All kidney transplant recipients between 2004 and
      2009 in our institution were analyzed (N = 254). Patients with CMV infection were
      included (N = 62). CMV infections were diagnosed with quantitative PCR. CMV D+/R-
      recipients received 6 months valganciclovir prophylaxis, after which DNAemia was
      monitored. After treatment, secondary prophylaxis with valganciclovir was given
      at the clinician's discretion for 2-26 weeks and CMV DNAemia was monitored.
      Altogether 43 reactivations and 19 primary infections occurred. Antiviral
      treatment with valganciclovir or ganciclovir was given to 45 patients; 34/62
      (55%) patients received secondary prophylaxis for mean 62 days (range 14-180
      days). CMV recurrence occurred in 14/43 (33%) seropositive patients and in 4/19
      (21%) patients after primary infection. In logistic regression, delayed graft
      function (OR 3.4) and high viral load (>100 000 copies/ml) at initial diagnosis
      (OR 5.9) predicted recurrence. Use or length of secondary prophylaxis, CMV
      serostatus, level of immunosuppression, HLA mismatch, antiviral treatment, or
      time to clearance of viremia during treatment did not predict recurrence of CMV.
      CMV recurrences occur commonly despite secondary prophylaxis. High viral load at
      diagnosis predicted the risk of recurrent CMV infection.

PMID- 21902726
TI  - Dental care and oral health in solid organ transplant recipients: a single center
      cross-sectional study and survey of German transplant centers.
AB  - Aim of this study was to collect information about oral health of patients before
      and after SOT as well as information about center-based recommendations for
      dental care. In a single center cross-sectional study, the oral situation of 20
      patients before and 20 after SOT were examined including dental (DMF-T),
      periodontal (PSR((r))/PSI), and oral hygiene findings (modified QHI). In a second
      project, a survey among 50 transplant centers in Germany was questioned regarding
      their recommendations for dental care of SOT recipients. Patients before and
      after SOT showed similar quality of dental findings (DMF-T), but worse compared
      to the general population. In addition, most patients in both groups showed
      pronounced periodontal treatment need (PSR((r))/PSI score 3 or 4). Oral hygiene
      findings (modified QHI) after SOT were significantly worse than in patients on
      the waiting list (P = 0.032). In a second project, the questionnaire was returned
      by 28 of 50 centers. Interpretation of data showed that 89% carry out a dental
      examination before SOT and 67% contacted the patients' dentists. After SOT, 83%
      of the transplant centers recommend antibiotic cover before dental measures. The
      results of our study revealed lacks in the dental care of SOT recipients.
      Consistent recommendations regarding the dental care of patients before and after
      SOT should be determined.

PMID- 21902727
TI  - Appointing 'trained donation practitioners' results in a higher family consent
      rate in the Netherlands: a multicenter study.
AB  - The consent process for organ and tissue donation is complex, both for families
      and professionals. To help professionals in broaching this subject we performed a
      multicenter study. We compared family consent to donation in three hospitals
      between December 2007 and December 2009. In the intervention hospital, trained
      donation practitioners (TDP) guided 66 families throughout the time in the ICU
      until a decision regarding donation had been reached. In the first control
      hospital, without any family guidance or training, 107 families were approached.
      In the second control hospital 'hostesses', who were not trained in donation
      questions, supported 99 families during admittance. A total of 272 families were
      requested to donate. We primarily compared consent rates, but also asked families
      about their experiences through a questionnaire. Family consent rate was
      significantly higher in the intervention hospital: 57.6% (38/66), than in the
      control hospitals: 34.6% (37/107) and 39.4% (39/99). The 69% response rate to the
      questionnaire -~5 months after death - showed no confounding variables that could
      have influenced the consent rate. Appointing TDPs in the intervention hospital to
      guide families during admittance and the donation decision-making process,
      results in higher family consent rates.

PMID- 21902728
TI  - Rationing life-saving resources--how should allocation policies be assessed in
      solid organ transplantation.
AB  - Because the demand for solid organ transplantation exceeds the availability of
      donated grafts, there needs to be rationing for this life-saving procedures.
      Criteria for selection of patients to a national transplant list and allocation
      of donated organs should be transparent yet there is no consistent approach to
      the development of such guidelines. It is suggested that selection and allocation
      policies should comply with minimum standards including defining of aims of the
      allocation process and desired outcome (whether maximizing benefit or utility or
      ensuring equity of access), inclusion and exclusion criteria, criteria for
      futility and suspension and removal from the transplant list, appeals processes,
      arrangements for monitoring and auditing outcomes and processes for dealing with
      noncompliance. Furthermore, guidelines must be consistent with legislation even
      though this may compete with public preference. Guidelines must be supported by
      all stakeholders (including health-care professionals, donor families and
      potential transplant candidates). However, there must also be flexibility to
      allow for exceptions and to support innovation and development.

PMID- 21902729
TI  - Pyoderma gangrenosum in a renal transplantation patient having immunosuppressive
      treatment for 5 years.

PMID- 21902730
TI  - Stimulating beta cell replication and improving islet graft function by GPR119
      agonists.
AB  - G protein-coupled receptor 119 (GPR119) is predominantly expressed in beta cells
      and intestinal L cells. In this study, we investigated whether oleoylethanolamide
      (OEA), a GPR119 endogenous ligand, and PSN632408, a GPR119 synthetic agonist, can
      stimulate beta-cell replication in vitro and in vivo and improve islet graft
      function in diabetic mice. We found that OEA and PSN632408 significantly
      increased numbers of insulin(+)/5-bromo-2'-deoxyuridine (BrdU)(+) beta cells in
      cultured mouse islets in a dose-dependent manner. All diabetic recipient mice,
      given marginal syngeneic islet transplants with OEA or PSN632408 or vehicle,
      achieved normoglycemia at 4 weeks after transplantation. However, normoglycemia
      was achieved significantly faster in OEA- or PSN632408-treated diabetic mice than
      in vehicle-treated diabetic mice (P < 0.05). The percentage of insulin(+)/BrdU(+)
      beta cells in islet grafts in OEA- and PSN632408-treated mice was significantly
      higher than in vehicle-treated mice (P < 0.01). Our data demonstrated that OEA
      and PSN632408 can stimulate beta-cell replication in vitro and in vivo and
      improve islet graft function. Targeting GPR119 is a novel therapeutic approach to
      increase beta-cell mass and to improve islet graft function by stimulating beta
      cell replication.

PMID- 21902731
TI  - Chronic rejection related to hepatitis B immunoglobulin discontinuation in a
      liver transplant recipient.

PMID- 21902732
TI  - Interaction between the reductase Tah18 and highly conserved Fe-S containing Dre2
      C-terminus is essential for yeast viability.
AB  - Tah18-Dre2 is a recently identified yeast protein complex, which is highly
      conserved in human and has been implicated in the regulation of oxidative stress
      induced cell death and in cytosolic Fe-S proteins synthesis. Tah18 is a diflavin
      oxido-reductase with binding sites for flavin mononucleotide, flavin adenine
      dinucleotide and nicotinamide adenine dinucleotide phosphate, which is able to
      transfer electrons to Dre2 Fe-S clusters. In this work we characterized in
      details the interaction between Tah18 and Dre2, and analysed how it conditions
      yeast viability. We show that Dre2 C-terminus interacts in vivo and in vitro with
      the flavin mononucleotide- and flavin adenine dinucleotide-binding sites of
      Tah18. Neither the absence of the electron donor nicotinamide adenine
      dinucleotide phosphate-binding domain in purified Tah18 nor the absence of Fe-S
      in aerobically purified Dre2 prevents the binding in vitro. In vivo, when this
      interaction is affected in a dre2 mutant, yeast viability is reduced. Conversely,
      enhancing artificially the interaction between mutated Dre2 and Tah18 restores
      cellular viability despite still reduced cytosolic Fe-S cluster biosynthesis. We
      conclude that Tah18-Dre2 interaction in vivo is essential for yeast viability.
      Our study may provide new insight into the survival/death switch involving this
      complex in yeast and in human cells.

PMID- 21902733
TI  - Dysregulation of serine biosynthesis contributes to the growth defect of a
      Mycobacterium tuberculosis crp mutant.
AB  - Mycobacterium tuberculosis CRP(Mt), encoded by Rv3676 (crp), is a CRP-like
      transcription factor that binds with the serC-Rv0885 intergenic region. In the
      present study, we evaluated CRP(Mt) 's regulation of serC and Rv0885 in M.
      tuberculosis and M. bovis BCG, using site-specific mutagenesis, promoter fusions
      and reverse-transcriptase PCR (RT-PCR). The CRP(Mt) binding site was required for
      full expression of serC and Rv0885, and expression of both genes was reduced in
      M. tuberculosis and M. bovis BCG crp mutants. These data show that CRP(Mt)
      binding directly activates both serC and Rv0885 expression. M. tuberculosis serC
      restored the ability of an Escherichia coli serC mutant to grow in serine-dropout
      medium, demonstrating that M. tuberculosis serC encodes a phosphoserine
      aminotransferase. Serine supplementation, or overexpression of serC, accelerated
      the growth of M. tuberculosis and M. bovis BCG crp mutants in mycomedium, but not
      within macrophages. These results establish a role for CRP(Mt) in the regulation
      of amino acid biosynthesis, and show that reduced serine production contributes
      to the slow-growth phenotype of M. tuberculosis and M. bovis BCG crp mutants in
      vitro. Restoration of serine biosynthesis by serC expression will facilitate
      identification of additional CRP(Mt)-regulated factors required by M.
      tuberculosis during macrophage and host infection.

PMID- 21902734
TI  - Arginine catabolic mobile element encoded speG abrogates the unique
      hypersensitivity of Staphylococcus aureus to exogenous polyamines.
AB  - Polyamines, including spermine (Spm) and spermidine (Spd), are aliphatic cations
      that are reportedly synthesized by all living organisms. They exert pleiotropic
      effects on cells and are required for efficient nucleic acid and protein
      synthesis. Here, we report that the human pathogen Staphylococcus aureus lacks
      identifiable polyamine biosynthetic genes, and consequently produces no Spm/Spd
      or their precursor compounds putrescine and agmatine. Moreover, while
      supplementing defined medium with polyamines generally enhances bacterial growth,
      Spm and Spd exert bactericidal effects on S. aureus at physiological
      concentrations. Small colony variants specifically lacking menaquinone
      biosynthesis arose after prolonged Spm exposure and exhibited reduced polyamine
      sensitivity. However, other respiratory-defective mutants were no less
      susceptible to Spm implying menaquinone itself rather than general respiration is
      required for full Spm toxicity. Polyamine hypersensitivity distinguishes S.
      aureus from other bacteria and is exhibited by all tested strains save those
      belonging to the USA-300 group of community-associated methicillin-resistant S.
      aureus (CA-MRSA). We identified one gene within the USA-300-specific arginine
      catabolic mobile element (ACME) encoding a Spm/Spd N-acetyltransferase that is
      necessary and sufficient for polyamine resistance. S. aureus encounters
      significant polyamine levels during infection; however, the acquisition of ACME
      encoded speG allows USA-300 clones to circumvent polyamine hypersensitivity, a
      peculiar trait of S. aureus.

PMID- 21902735
TI  - Practitioner and lay perspectives of the service provision of nutrition
      information leaflets in primary care.
AB  - BACKGROUND: In primary care, leaflets are often used to communicate health
      information. Increasingly, primary healthcare practitioners need to provide
      dietary advice. There is limited research exploring how nutrition information
      leaflets are used in primary care. The present study explored practitioner and
      lay experiences with respect to providing and receiving nutrition information in
      primary care, focusing in particular on the use of leaflets for nutrition
      information. METHODS: A qualitative design was used incorporating focus groups
      with 57 practitioners based at seven general practitioner practices and a
      purposive sample of 30 lay participants attending six Consumer Health
      Organisations within one primary care trust. Focus groups were taped and
      transcribed verbatim and data were analysed thematically, assisted by computer
      software n6(r) (QSR International Pty Ltd, Melbourne, Australia). RESULTS:
      Practitioners discussed barriers to giving nutritional advice, access to
      leaflets, lay receptiveness to advice and their perceptions about the value of
      leaflets to lay people. Food was not considered in terms of its nutritional
      components by lay participants and the need for nutritional information was not
      perceived to be relevant until they had received a medical diagnosis. Lay
      participants discussed the importance of receiving nutritional advice relating to
      their medical diagnosis and the altered status of written information that was
      delivered personally. Practitioner and lay groups suggested improvements to
      ensure that nutritional advice be supported by relevant and appropriate written
      information. CONCLUSIONS: This research has underlined the continuing importance
      of nutrition information leaflets and concludes that there is particular value in
      involving lay participants in the development of nutrition information leaflets.

PMID- 21902736
TI  - Medical, demographic and social cognitive correlates of physical activity in a
      population-based sample of colorectal cancer survivors.
AB  - Physical activity (PA) improves quality of life in colorectal cancer survivors
      (CRC) and may reduce the risk of disease recurrence and early death. Few studies,
      however, have examined the correlates of PA in CRC survivors. Using the Alberta
      Cancer Registry, 2000 randomly selected CRC survivors were mailed a self-reported
      questionnaire assessing medical, demographic, behavioural and social cognitive
      variables from the theory of planned behaviour (TPB). Of the 600 survivors who
      responded, 33% were meeting public health PA guidelines and almost half were
      completely sedentary. Higher PA was reported by survivors who were younger,
      unmarried, better educated, wealthier, employed, non-smokers, social drinkers,
      not treated with radiation therapy, disease-free, in better health and less
      comorbidity. In multivariate path analysis, these variables were not directly
      associated with PA after controlling for the TPB variables. The TPB explained 34%
      (P < 0.001) of the variance in PA behaviour with direct associations for
      intention (beta= 0.22; P= 0.015) and planning (beta= 0.18; P= 0.001). Intention,
      in turn, had 62% (P < 0.001) of its variance explained by perceived behavioural
      control (beta= 0.43; P < 0.001), affective attitude (beta= 0.25; P < 0.001) and
      instrumental attitude (beta= 0.15; P < 0.001). The TPB may be a useful framework
      for developing population-based interventions to increase PA in CRC survivors.

PMID- 21902740
TI  - Development of a psychosocial adaptation questionnaire for Chinese patients with
      visual impairments.
AB  - AIM: To develop a psychosocial adaptation questionnaire for Chinese patients with
      visual impairments and to examine its reliability and validity. BACKGROUND:
      Psychosocial adaptation with disease has been studied, however, there have been
      few reports on the impact of visual impairment on psychosocial adaptation. An
      instrument has not been developed to assess psychosocial adaptation with visual
      impairment specifically for patients in China. METHODS: Both qualitative and
      quantitative research methods were used. A questionnaire was developed based on
      the concept of psychosocial adaptation with visual impairment. Items for the
      questionnaire were developed by reviewing the literature and carrying out a semi
      structured interview with 12 visually impaired patients. Five ophthalmologists
      and ten patients evaluated the content validity and face validity of the
      questionnaire, respectively. The method of convenient sampling was used to select
      213 visually impaired patients in the Ophthalmology Department of the First
      Affiliated Hospital of China Medical University to participate in the study.
      Discriminative index and item-total correlation analyses were used to delete
      items that were lower than a set criterion. Regarding construct validity, factor
      analysis was performed. The Self-rating Anxiety Scale (SAS), General Self
      Efficacy Scale (GSES) and Self Acceptance Questionnaire (SAQ) were used to
      evaluate criterion validity. Cronbach's alpha coefficient was used as an index of
      internal consistency. To evaluate test-retest reliability, 50 patients were re
      evaluated after 24 hours. RESULTS: A total of 204 questionnaire items were
      created. 22 items were deleted by discriminative index and item-total correlation
      before factor analysis; 38 items were entered into the model for factor analysis.
      Seven factors were extracted by using principal factor analysis and varimax
      rotation, with a cumulative contribution of 59.18%. The correlation coefficients
      between the psychosocial adaptation questionnaire for visual impairment and the
      SAS, GSES and SAQ were -0.771, 0.754 and 0.722, respectively (p < 0.01). The
      Cronbach's alpha coefficient for the psychosocial adaptation questionnaire was
      0.948. The alpha coefficients of seven sub-questionnaires ranged from 0.56-0.89.
      The correlation coefficients for the total questionnaire and seven sub
      questionnaires ranged from 0.97-0.99 (p < 0.01). CONCLUSION: The results of this
      study confirmed the reliability and validity of the 38-item psychosocial
      adaptation questionnaire for the visually impaired in China. It therefore can be
      used as a measurement tool for widespread, cost-effective clinical assessment and
      further research. RELEVANCE TO CLINICAL PRACTICE: The new tool may help nurses
      and other clinical personnel to evaluate the psychosocial adaptation of visually
      impaired patients and provide a suitable basis for assisting with adaptation to
      visual impairment and enhancing quality of life.

PMID- 21902741
TI  - Commentary on Smith GD (2011) editorial: Evaluation of CAM interventions. Journal
      of Clinical Nursing 20, 921-922.

PMID- 21902742
TI  - Commentary on Lin MF, Hsieh YJ, Fetzer S & Hsu MC (2011) A randomised controlled
      trial of the effect of music therapy and verbal relaxation on chemotherapy
      induced anxiety. Journal of Clinical Nursing 20, 988-999.

PMID- 21902743
TI  - Tracing the recombination and colonization history of hybrid species in space and
      time.
AB  - Hybrid speciation has long fascinated evolutionary biologists and laymen alike,
      presumably because it challenges our classical view of evolution as a 'one-way
      street' leading to strictly tree-like patterns of ancestry and descent. Homoploid
      hybrid speciation (HHS) has been a particularly interesting puzzle, as it appears
      to occur extremely rapidly, perhaps within less than 50 generations (McCarthy et
      al. 1995; Buerkle et al. 2000). Nevertheless, HHS may sometimes involve extended
      or repeated periods of recombination and gene exchange between populations
      subject to strong divergent natural selection (Buerkle & Rieseberg 2008). Thus,
      HHS provides a highly interesting setting for understanding the drivers and tempo
      of adaptive divergence and speciation in the face of gene flow (Arnold 2006;
      Rieseberg & Willis 2007; Nolte & Tautz 2009). In the present issue of Molecular
      Ecology, Wang et al. (2011) explore a particularly challenging issue connected to
      HHS: they attempt to trace the colonization and recombination history of an
      ancient (several MYA) hybrid species, from admixture and recombination in the
      ancestral hybrid zone to subsequent range shifts triggered by tectonic events
      (uplift of the Tibetan plateau) and climatic shifts (Pleistocene ice ages). This
      work is important because it addresses key issues related to the origin of the
      standing genetic variation available for adaptive responses (e.g. to climate
      change) and speciation in temperate species, which are topics of great current
      interest (Rieseberg et al. 2003; Barrett & Schluter 2008; de Carvalho et al.
      2010).

PMID- 21902744
TI  - Hybrid speciation in birds: allopatry more important than ecology?
AB  - Hybrid speciation was once thought to be rare in animals, but over the past
      decade, improved molecular analysis techniques and increased research attention
      have allowed scientists to uncover many examples. In this issue, two papers
      (Elgvin et al. 2011; Hermansen et al. 2011) present compelling evidence for the
      hybrid origin of the Italian sparrow based on nuclear and mitochondrial DNA
      sequences, microsatellites, and plumage coloration. These studies point to an
      important role for geographic isolation in the process of hybrid speciation, and
      provide a starting point for closer examination of the genetic and behavioural
      mechanisms involved.

PMID- 21902745
TI  - Fungal farmers or algal escorts: lichen adaptation from the algal perspective.
AB  - Domestication of algae by lichen-forming fungi describes the symbiotic
      relationship between the photosynthetic (green alga or cyanobacterium;
      photobiont) and fungal (mycobiont) partnership in lichen associations (Goward
      1992). The algal domestication implies that the mycobiont cultivates the alga as
      a monoculture within its thallus, analogous to a farmer cultivating a food crop.
      However, the initial photobiont 'selection' by the mycobiont may be predetermined
      by the habitat rather than by the farmer. When the mycobiont selects a photobiont
      from the available photobionts within a habitat, the mycobiont may influence
      photobiont growth and reproduction (Ahmadjian & Jacobs 1981) only after the
      interaction has been initiated. The theory of ecological guilds (Rikkinen et al.
      2002) proposes that habitat limits the variety of photobionts available to the
      fungal partner. While some studies provide evidence to support the theory of
      ecological guilds in cyanobacterial lichens (Rikkinen et al. 2002), other studies
      propose models to explain variation in symbiont combinations in green algal
      lichens (Ohmura et al. 2006; Piercey-Normore 2006; Yahr et al. 2006)
      hypothesizing the existence of such guilds. In this issue of Molecular Ecology,
      Peksa & Skaloud (2011) test the theory of ecological guilds and suggest a
      relationship between algal habitat requirements and lichen adaptation in green
      algal lichens of the genus Lepraria. The environmental parameters examined in
      this study, exposure to rainfall, altitude and substratum type, are integral to
      lichen biology. Lichens have a poikilohydric nature, relying on the availability
      of atmospheric moisture for metabolic processes. Having no known active mechanism
      to preserve metabolic thallus moisture in times of drought, one would expect a
      strong influence of the environment on symbiont adaptation to specific habitats.
      Adaptation to changes in substrata and its properties would be expected with the
      intimate contact between crustose lichens in the genus Lepraria. Altitude has
      been suggested to influence species distributions in a wide range of taxonomic
      groups. This is one of the first studies to illustrate an ecological guild,
      mainly for exposure to rainfall (ombrophiles and ombrophobes), with green algal
      lichens.

PMID- 21902746
TI  - Genetic architecture of life history traits and environment-specific trade-offs.
AB  - Life history theory predicts the evolution of trait combinations that enhance
      fitness, and the occurrence of trade-offs depends in part on the magnitude of
      variation in growth rate or acquisition. Using recombinant inbred lines, we
      examined the genetic architecture of age and size at reproduction across abiotic
      conditions encountered by cultivars and naturalized populations of Brassica rapa.
      We found that genotypes are plastic to seasonal setting, such that reproduction
      was accelerated under conditions encountered by summer annual populations and
      genetic variances for age at reproduction varied across simulated seasonal
      settings. Using an acquisition-allocation model, we predicted the likelihood of
      trade-offs. Consistent with predicted relationships, we observed a trade-off
      where early maturity is associated with small size at maturity under simulated
      summer and fall annual conditions but not under winter annual conditions. The
      trade-off in the summer annual setting was observed despite significant genotypic
      variation in growth rate, which is often expected to decouple age and size at
      reproduction because rapidly growing genotypes could mature early and attain a
      larger size relative to slowly growing genotypes that mature later. The absence
      of a trade-off in the winter setting is presumably attributable to the absence of
      genotypic differences in age at reproduction. We observed QTL for age at
      reproduction that jointly regulated size at reproduction in both the summer and
      fall annual settings, but these QTL were environment-specific (i.e. different QTL
      contributed to the trade-off in the fall vs. summer annual settings). Thus, at
      least some of the genetic mechanisms underlying observed trade-offs differed
      across environments.

PMID- 21902748
TI  - Genome-wide analysis of alternative reproductive phenotypes in honeybee workers.
AB  - A defining feature of social insects is the reproductive division of labour, in
      which workers usually forego all reproduction to help their mother queen to
      reproduce. However, little is known about the molecular basis of this spectacular
      form of altruism. Here, we compared gene expression patterns between
      nonreproductive, altruistic workers and reproductive, non-altruistic workers in
      queenless honeybee colonies using a whole-genome microarray analysis. Our results
      demonstrate massive differences in gene expression patterns between these two
      sets of workers, with a total of 1292 genes being differentially expressed. In
      nonreproductive workers, genes associated with energy metabolism and respiration,
      flight and foraging behaviour, detection of visible light, flight and heart
      muscle contraction and synaptic transmission were overexpressed relative to
      reproductive workers. This implies they probably had a higher whole-body energy
      metabolism and activity rate and were most likely actively foraging, whereas same
      aged reproductive workers were not. This pattern is predicted from evolutionary
      theory, given that reproductive workers should be less willing to compromise
      their reproductive futures by carrying out high-risk tasks such as foraging or
      other energetically expensive tasks. By contrast, reproductive workers mainly
      overexpressed oogenesis-related genes compared to nonreproductive ones. With
      respect to key switches for ovary activation, several genes involved in steroid
      biosynthesis were upregulated in reproductive workers, as well as genes known to
      respond to queen and brood pheromones, genes involved in TOR and insulin
      signalling pathways and genes located within quantitative trait loci associated
      with reproductive capacity in honeybees. Overall, our results provide unique
      insight into the molecular mechanisms underlying alternative reproductive
      phenotypes in honeybee workers.

PMID- 21902747
TI  - Female influence on pre- and post-copulatory sexual selection and its genetic
      basis in Drosophila melanogaster.
AB  - Genetic variation among females is likely to influence the outcome of both pre-
      and post-copulatory sexual selection in Drosophila melanogaster. Here we use
      association testing to survey natural variation in 10 candidate female genes for
      their effects on female reproduction. Females from 91 chromosome two substitution
      lines were scored for phenotypes affecting pre- and post-copulatory sexual
      selection such as mating and remating rate, propensity to use sperm from the
      second male to mate, and measures of fertility. There were significant genetic
      contributions to phenotypic variation for all the traits measured. Resequencing
      of the 10 candidate genes in the 91 lines yielded 68 non-synonymous polymorphisms
      which were tested for associations with the measured phenotypes. Twelve
      significant associations (markerwise P<0.01) were identified. Polymorphisms in
      the putative serine protease homolog CG9897 and the putative odorant binding
      protein CG11797 associated with female propensity to remate and met an
      experimentwise significance of P<0.05. Several other associations, including
      those impacting both fertility and female remating rate suggest that sperm
      storage might be an important factor mitigating female influence on sexual
      selection.

PMID- 21902749
TI  - Costs and benefits of polyandry in a placental poeciliid fish Heterandria formosa
      are in accordance with the parent-offspring conflict theory of placentation.
AB  - In viviparous species, a conflict over maternal resource allocation may arise
      between mothers and embryos, between siblings, and between maternal and paternal
      genes within an embryo due to relatedness asymmetries. We performed two
      experiments to study the effects of polyandry and brood relatedness on offspring
      growth in a placental fish (Heterandria formosa). Polyandry was beneficial as it
      increased the probability of pregnancy, possibly to avoid genetic
      incompatibility. However, females mated to four males produced offspring that had
      a longer maturation time than those of monandrous females. When within-brood
      relatedness was manipulated, the size of the newborn offspring decreased with
      time in low-relatedness treatment, whereas in highly related broods, offspring
      size was constant. Low within-brood relatedness may lead to less cooperative
      offspring in terms of resource extraction from the mother, which may lead to
      impaired development during gestation. Offspring conflict may thus reduce the
      benefits of polyandry in viviparous species.

PMID- 21902750
TI  - Pulsed-resource dynamics increase the asymmetry of antagonistic coevolution
      between a predatory protist and a prey bacterium.
AB  - Temporal resource fluctuations could affect the strength of antagonistic
      coevolution through population dynamics and costs of adaptation. We studied this
      by coevolving the prey bacterium Serratia marcescens with the predatory protozoa
      Tetrahymena thermophila in constant and pulsed-resource environments for
      approximately 1300 prey generations. Consistent with arms race theory, the prey
      evolved to be more defended, whereas the predator evolved to be more efficient in
      consuming the bacteria. Coevolutionary adaptations were costly in terms of
      reduced prey growth in resource-limited conditions and less efficient predator
      growth on nonliving resource medium. However, no differences in mean
      coevolutionary changes or adaptive costs were observed between environments, even
      though resource pulses increased fluctuations and mean densities of coevolving
      predator populations. Interestingly, a surface-associated prey defence mechanism
      (bacterial biofilm), to which predators were probably unable to counter-adapt,
      evolved to be stronger in pulsed-resource environment. These results suggest that
      temporal resource fluctuations can increase the asymmetry of antagonistic
      coevolution by imposing stronger selection on one of the interacting species.

PMID- 21902751
TI  - Resolving current disagreements and ambiguities in the terminology of animal
      communication.
AB  - Communication is central to most interactions between organisms. There is
      currently considerable controversy about the evolution, function and even about
      the most basic definition of communication. The controversy is linked to
      definitional ambiguities and disagreements. Here we discuss how some recent
      disagreements can be resolved and offer a clear set of definitions. Central to
      our approach is a definition of communication as being a trade between one
      organism (the informer) and another (the perceiver). The informer exerts
      influence on the perceiver through the communication process, and the perceiver
      experiences a change in its informational state (that is, gains information) as a
      consequence of detecting the communication. We define both influence and
      information explicitly and delineate between signalling, deceptive communication,
      and situations where perceivers respond to cues rather than signals. We
      demonstrate how our definitions allow resolution of conflicts arising in recent
      publications on the definitions on communication and related terms.

PMID- 21902752
TI  - Use of deferiprone for iron chelation in patients with transfusion-dependent
      thalassaemia.
AB  - AIM: To conduct a retrospective case analysis of the clinical efficacy and
      adverse effects of deferiprone in our population. METHODS: All patients with
      transfusion-dependent thalassaemia at KK Hospital who have been on deferiprone
      were included in the study. Outcomes measured include the change in ferritin
      levels and cardiac T2* values during deferiprone therapy, and incidence of side
      effects. RESULTS: Thirty-three (47.1%) of the total cohort of 70 patients have
      been on deferiprone, out of which 26 were on combination therapy with
      desferrioxamine. Majority of the patients (76%) had stable cardiac iron load
      during deferiprone therapy, and four patients with moderate to severe cardiac
      iron load showed improvement. Ten patients (30.3%) had improvement in their
      ferritin levels. Three patients (9.1%) developed mild neutropenia at 3, 18 and 26
      months, respectively, and two patients (6.1%) had agranulocytosis at 4 and 10
      months, respectively. Their neutrophil counts improved spontaneously after
      cessation of deferiprone. Thrombocytopenia developed in 27.3% of the patients and
      was transient in majority (77.8%) of the patients. Five patients (15.2%)
      developed arthritis that improved after cessation of deferiprone therapy, and one
      patient had transient arthralgia that resolved spontaneously. Three patients
      (9.1%) had nausea and abdominal pain. CONCLUSION: Deferiprone effectively reduced
      or stabilised cardiac iron load in our patients. Thrombocytopenia, arthropathy,
      neutropenia and agranulocytosis are the most important side effects. It is
      recommended that patients on deferiprone have their full blood counts monitored
      weekly for the first year of therapy and subsequently fortnightly as long as they
      are on deferiprone.

PMID- 21902753
TI  - High incidence of obesity co-morbidities in young children: a cross-sectional
      study.
AB  - AIM: The prevalence of overweight and obesity in children is a public health
      problem because of future morbidity. However, the prevalence of medical
      complications in overweight and obese primary school children in Australia is not
      well documented. As part of the larger, prospective cohort Growth and Development
      Study, this report aimed to identify the medical complications of obesity in a
      population-based community sample of primary school-aged children. METHODS: Two
      groups of primary school children were studied: a random community sample of
      overweight/obese children (not seeking treatment) and a matched community sample
      of normal weight children. Demographics, medical history, family history and
      symptoms of complications of overweight were collected. Children had a physical
      examination, oral glucose tolerance tests with insulins, fasting lipid profiles
      and liver function tests. RESULTS: Data from 283 children are presented (6.1-13.4
      years, mean 9.8 years). There were no differences in birth data, family
      composition, parental age or socio-economic status between groups. Overweight and
      obese children were more likely to complain of musculoskeletal pain, depression,
      anxiety and bullying, and had more adverse examination findings than control
      children. They also had more abnormal investigations: overweight children:
      impaired glucose tolerance (IGT) 1.3%, hyperinsulinism 19.5%, dyslipidaemia
      63.8%, raised alanine transaminase (ALT) 9.0%; obese children: IGT 5.3%,
      hyperinsulinism 38.9%, dyslipidaemia 73.7%, raised ALT 31.6%. CONCLUSION:
      Overweight and obese primary school-aged children have significant medical
      complications of their weight status. Overweight children, in addition to obese
      children, should be screened for complications. A secondary finding is a high
      proportion of normal weight children with lipid levels outside desirable healthy
      ranges.

PMID- 21902754
TI  - Challenging Ronald: McDonald versus McDonald's.
AB  - Obesity is the most prevalent health condition affecting first world children in
      2011. This article recounts a campaign that opposed the construction of a fast
      food outlet in close proximity to a large school complex. The epidemiologic
      evidence that there is a negative health impact on children that attend schools
      close to fast food outlets is reiterated. There is an urgent need for planning
      laws to be modernised to reflect that evidence.

PMID- 21902755
TI  - Author's reply: most HIV Transmission in sub-Saharan Africa occurs through sex.

PMID- 21902756
TI  - Vascular endothelial growth factor gene polymorphisms in spontaneously aborted
      fetuses.
AB  - PROBLEMS: The VEGF-1154G>A polymorphism has been reported to be a genetic risk
      factor for recurrent spontaneous abortion in various studies; however, these
      studies have focused on genetic analyses of pregnant women rather than aborted
      fetuses. To evaluate and confirm the association between the VEGF-1154G>A
      polymorphism and spontaneous abortion, we focused on the relationship between
      four polymorphisms in the VEGF gene (-2578C>A, -1154G>A, -634G>C, and 936C>T) and
      spontaneously aborted fetuses (SAFs). METHOD OF STUDY: The subjects included 118
      SAFs at <20 weeks gestation and 380 normal controls consisting of children and
      adults. The polymorphisms were genotyped by polymerase chain reaction-restriction
      fragment length polymorphism analysis. RESULTS: Spontaneously aborted fetuses
      exhibited significantly different frequencies of the -2578CA+AA/-634CC and 
      1154GA+AA/-634CC combined genotypes compared with control subjects. The frequency
      of the -2578A/-1154A/-634C/936C haplotype was significantly higher in SAFs.
      CONCLUSIONS: VEGF genes -2578CA+AA/-634CC and -1154GA+AA/-634CC in the fetus are
      possible risk factors for spontaneous abortion.

PMID- 21902765
TI  - Mechanism of onset and exacerbation of chronic glomerulonephritis and its
      treatment.
AB  - Immunoglobulin A nephropathy (IgAN) is one of the most common causes of chronic
      glomerulonephritis (CGN) in the world. The proliferative and crescentic forms of
      IgA are found in up to 30% of cases and are associated with nephritic-range
      proteinuria, accelerated hypertension, and accelerated decline toward end-stage
      renal disease. On the other hand, Henoch-Schonlein purpura (HSP) is a systemic
      disorder characterized by leukocytoclastic vasculitis involving the capillaries
      and the deposition of IgA immune complexes. Renal involvement is the principal
      cause of morbidity and mortality in children with HSP. Two entity diseases are
      important as renal diseases in childhood. We herein review the mechanism of the
      onset and exacerbation of IgAN and HSP nephritis (HSPN) and its treatment. As to
      the pathogenesis, we found that CB4 provoked exacerbation of renal pathologic
      findings in hyper IgA mice via endothelial injury, gamma-interferon production,
      and dysfunction of the mesangial pathway and could possibly become one of the
      factors involved in the mechanism of the onset or evolution of human IgAN. As to
      the treatment of IgAN and HSPN, we evaluated the efficacy of multidrug
      combination therapy (prednisolone, warfarin, and dipyridamole, including
      mizoribine) for diffuse IgAN and the efficacy of methylprednisolone and urokinase
      pulse therapy plus immunosuppressive drugs for severe HSPN in children. These
      therapies were effective in ameliorating the proteinuria and histologic severity
      of patients with IgAN or HSPN. In future, detailed investigations into the
      pathogenesis of CGN and double-blind randomized control studies on children with
      IgAN or HSPN will be necessary.

PMID- 21902766
TI  - G-protein beta3 subunit 825CC genotype is associated with postprandial distress
      syndrome with impaired gastric emptying and with the feeling of hunger in
      Japanese.
AB  - BACKGROUND: G-protein dysfunction related alteration of intracellular signal
      transduction might be linked to various abnormalities of functional
      gastrointestinal (GI) disorders. Serotonin (5-hydroxytryptamine; 5-HT) as well as
      G-protein is also key signaling molecule sensorimotor functions in the GI tract.
      Thus, this study aims to evaluate the correlation between gastric emptying and
      GNbeta3 and 5-HTs polymorphisms in functional dyspepsia (FD) as defined by Rome
      III classification. METHODS: Seventy-four patients presenting with typical
      symptoms of FD (epigastric pain syndrome: EPS, n=24; postprandial distress
      syndrome: PDS, n = 51) and sixty-four healthy volunteers were enrolled. Gastric
      motility was evaluated with the T(max) value using the (13) C-acetate breath
      test. We used Rome III criteria to evaluate upper abdominal symptoms and SRQ-D
      scores to determine depression status. GNbeta3-C825T, 5-HT(1A) -C1019G, 5-HT(2A) 
      G1438A, 5-HT(3A) -C42T, and 5-HT(4A) -G353+6A polymorphisms were analyzed in DNA
      from blood samples of enrolled subjects. Genotyping was performed by polymerase
      chain reaction. KEY RESULTS: There was a significant relationship (P=0.045)
      between GNbeta3 825CC genotype and PDS patients without gastro-esophageal reflux
      symptoms with impaired gastric emptying. In Japanese, GNbeta3 825CC genotype in
      FD patients was significantly associated (P=0.0485) with the feeling of hunger
      compared with GNbeta3 825CT and TT genotypes. CONCLUSIONS & INFERENCES:   Our
      results suggest that the GNbeta3 825CC genotype is significantly associated with
      PDS patients without gastro-esophageal reflux with impairments of gastric
      emptying and also with the feeling of hunger in patients with FD. Further studies
      are needed to clarify whether the GNbeta3 825CC genotype is linked to
      disturbances of gastric emptying via altered signal transduction responses.

PMID- 21902767
TI  - Helicobacter pylori and autoimmune diseases.
AB  - Helicobacter pylori (H. pylori) is a widely prevalent microbe, with between 50
      and 80% of the population infected worldwide. Clinically, infection with H.
      pylori is commonly associated with peptic ulcer disease, but many of those
      infected remain asymptomatic. H. pylori has evolved a number of means to affect
      the host immune response and has been implicated in many diseases mitigated by
      immune dysregulation, such as immune thrombocytopenic purpura (ITP), atrophic
      gastritis, and mucosa associated lymphoid tissue (MALT) lymphoma. Autoimmune
      diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and
      Sjogren's syndrome, are the result of a dysregulated host immune system which
      targets otherwise healthy tissues. The exact etiology of autoimmune diseases is
      unclear, but it has long been suggested that exposure to certain environmental
      agents, such as viral and bacterial infection or chemical exposures, in
      genetically susceptible individuals may be the catalyst for the initiation of
      autoimmune processes. Because of its prevalence and ability to affect human
      immune function, many researchers have hypothesized that H. pylori might
      contribute to the development of autoimmune diseases. In this article, we review
      the available literature regarding the role of chronic H. pylori infection in
      various autoimmune disease states.

PMID- 21902768
TI  - Marathon of eponyms: 21 Urbach-Wiethe disease (Lipoid proteinosis).
AB  - The use of eponyms has long been contentious, but many remain in common use, as
      discussed elsewhere (Editorial: Oral Diseases. 2009: 15; 185). The use of eponyms
      in diseases of the head and neck is found mainly in specialties dealing with
      medically compromised individuals (paediatric dentistry, special care dentistry,
      oral and maxillofacial medicine, oral and maxillofacial pathology, oral and
      maxillofacial radiology and oral and maxillofacial surgery) and particularly by
      hospital-centred practitioners. This series has selected some of the more
      recognized relevant eponymous conditions and presents them alphabetically. The
      information is based largely on data available from MEDLINE and a number of
      internet websites as noted below: the authors would welcome any corrections. This
      document summarizes data about Urbach-Wiethe disease.

PMID- 21902769
TI  - The oral microbiome in health and disease and the potential impact on
      personalized dental medicine.
AB  - Every human body contains a personalized microbiome that is essential to
      maintaining health but capable of eliciting disease. The oral microbiome is
      particularly imperative to health because it can cause both oral and systemic
      disease. The oral microbiome rests within biofilms throughout the oral cavity,
      forming an ecosystem that maintains health when in equilibrium. However, certain
      ecological shifts in the microbiome allow pathogens to manifest and cause
      disease. Severe forms of oral disease may result in systemic disease at different
      body sites. Microbiomics and metagenomics are two fields of research that have
      emerged to identify the presence of specific microbes in the body and understand
      the nature of the microbiome activity during both health and disease. The
      analysis of the microbiome and its genomes will pave the way for more effective
      therapeutic and diagnostic techniques and, ultimately, contribute to the
      development of personalized medicine and personalized dental medicine.

PMID- 21902770
TI  - On the suitability of fast and frugal heuristics for designing values
      clarification methods in patient decision aids: a critical analysis.
AB  - BACKGROUND: Increasingly, patient decision aids and values clarification methods
      (VCMs) are being developed to support patients in making preference-sensitive
      health-care decisions. Many VCMs encourage extensive deliberation about options,
      without solid theoretical or empirical evidence showing that deliberation is
      advantageous. Research suggests that simple, fast and frugal heuristic decision
      strategies sometimes result in better judgments and decisions. Durand et al. have
      developed two fast and frugal heuristic-based VCMs. OBJECTIVE: To critically
      analyse the suitability of the 'take the best' (TTB) and 'tallying' fast and
      frugal heuristics in the context of patient decision making. STRATEGY: Analysis
      of the structural similarities between the environments in which the TTB and
      tallying heuristics have been proven successful and the context of patient
      decision making and of the potential of these heuristic decision processes to
      support patient decision making. CONCLUSION: The specific nature of patient
      preference-sensitive decision making does not seem to resemble environments in
      which the TTB and tallying heuristics have proven successful. Encouraging
      patients to consider less rather than more relevant information potentially even
      deteriorates their values clarification process. Values clarification methods
      promoting the use of more intuitive decision strategies may sometimes be more
      effective. Nevertheless, we strongly recommend further theoretical thinking about
      the expected value of such heuristics and of other more intuitive decision
      strategies in this context, as well as empirical assessments of the mechanisms by
      which inducing such decision strategies may impact the quality and outcome of
      values clarification.

PMID- 21902771
TI  - The use of formal and informal knowledge sources in patients' treatment decisions
      in secondary stroke prevention: qualitative study.
AB  - BACKGROUND: There is robust empirical evidence to support clinical decision
      making in secondary stroke prevention after transient ischaemic attack (TIA) or
      recovered stroke. However, little attention has been paid to patients'
      utilization of this evidence in coming to decisions about their treatment
      choices. OBJECTIVE: To examine the use of formal and informal knowledge by
      patients in making decisions about carotid endarterectomy (CEA) and medical
      treatment after TIA/recovered stroke. SETTING AND PARTICIPANTS: Twenty
      participants were recruited from an outpatient vascular surgical assessment
      clinic in England. Ten were receiving medical treatment alone, and 10 were
      undergoing CEA after TIA or recovered stroke. METHOD: Twenty-eight in-depth
      qualitative interviews were conducted. An iterative approach was used whereby
      emergent themes were further explored in later interviews. Interviews were
      audiotaped, transcribed and coded. RESULTS: Participants gathered and utilized
      several types of knowledge in the process of making treatment decisions:
      Empirical knowledge (e.g. clinical trial findings); Pathophysiologic findings
      (e.g., results of clinical investigations); Experiential knowledge (e.g.,
      personal experience of stroke); Goals and values (e.g., potential impact on
      family); System features (e.g., apparent urgency of treatment). CONCLUSIONS: In
      addition to formal evidence, patients use other sources of informal or 'non
      evidentiary' knowledge to support their decisions about treatment after TIA or
      recovered stroke. To enable evidence-based patient choice, health professionals
      need to appreciate the diverse types of evidence which patients use, to help them
      to access relevant and high-quality evidence, to balance evidence from different
      sources and to make choices which are congruent with their values and
      expectations.

PMID- 21902772
TI  - The impact of patient and public involvement in the work of the Dementias &
      Neurodegenerative Diseases Research Network (DeNDRoN): case studies.
AB  - AIMS: (i) To describe patient and public involvement (PPI) in a network promoting
      research in dementia and neurodegenerative diseases, in terms of activity at the
      different stages of the research cycle and within the different levels of the
      research network. (ii) To use case studies to try and answer the question: what
      benefits (if any) does PPI in research bring to the research process? BACKGROUND:
      PPI in health research is a central part of government policy, but the evidence
      base underpinning it needs strengthening. PPI allows exploration of feasibility,
      acceptability and relevance of hypotheses, assists in the precise definition of
      research questions and increases accrual to studies. However, the measurement of
      outcomes is methodologically difficult, because the impact of lay researchers may
      occur through team interactions and be difficult to untangle from the efforts of
      professional researchers. Opportunities for PPI in rapidly progressive diseases
      may be limited, and involvement of people with marked cognitive impairment is
      particularly challenging. DESIGN: (i) Description of PPI within the DeNDRoN
      network. (ii) Case studies of three research projects which asked for extra help
      from centrally organized PPI. RESULTS: PPI in research projects on the DeNDRoN
      portfolio may function at different levels, occurring at project, local research
      network and national level. Case studies of three research projects show
      different roles for PPI in research and different functions for centrally
      organized PPI, including contribution to remedial action in studies that are not
      recruiting to target, solving problems because of the complexity and sensitivity
      of the research topic, and linking researchers to PPI resources. DISCUSSION: The
      case studies suggest that centrally organized PPI can have 'diagnostic' and
      remedial functions in studies that are struggling to recruit and serve as
      reinforcement for study-level PPI in the complex and sensitive research topics
      that are typical in neurodegenerative diseases research. PPI may be actively
      sought by researchers, but the infrastructure of PPI is not yet so widespread in
      the research community that lay researchers are easy to find; a centrally
      organized PPI resource can assist in this situation.

PMID- 21902773
TI  - Provider perspectives on the utility of a colorectal cancer screening decision
      aid for facilitating shared decision making.
AB  - BACKGROUND: Decision aids for colorectal cancer (CRC) screening have been shown
      to enable patients to identify a preferred screening option, but the extent to
      which such tools facilitate shared decision making (SDM) from the perspective of
      the provider is less well established. OBJECTIVE: Our goal was to elicit provider
      feedback regarding the impact of a CRC screening decision aid on SDM in the
      primary care setting. METHODS: Cross-sectional survey. PARTICIPANTS: Primary care
      providers participating in a clinical trial evaluating the impact of a novel CRC
      screening decision aid on SDM and adherence. MAIN OUTCOMES: Perceptions of the
      impact of the tool on decision-making and implementation issues. RESULTS: Twenty
      nine of 42 (71%) eligible providers responded, including 27 internists and two
      nurse practitioners. The majority (>60%) felt that use of the tool complimented
      their usual approach, increased patient knowledge, helped patients identify a
      preferred screening option, improved the quality of decision making, saved time
      and increased patients' desire to get screened. Respondents were more neutral is
      their assessment of whether the tool improved the overall quality of the patient
      visit or patient satisfaction. Fewer than 50% felt that the tool would be easy to
      implement into their practices or that it would be widely used by their
      colleagues. CONCLUSION: Decision aids for CRC screening can improve the quality
      and efficiency of SDM from the provider perspective but future use is likely to
      depend on the extent to which barriers to implementation can be addressed.

PMID- 21902774
TI  - The process of social participation in primary health care: the case of Palencia,
      Guatemala.
AB  - BACKGROUND: In 2008, the World Health Organization issued a callback to the
      principles of primary health care, which renewed interests in social
      participation in health. In Guatemala, social participation has been the main
      policy for the decentralization process since the late 1990s and the social
      development council scheme has been the main means for participation for the
      country's population since 2002. AIM: The aim of this study was to explore the
      process of social participation at a municipal-level health commission in the
      municipality of Palencia, Guatemala. METHODS: Analysis of legal and policy
      documents and in-depth interviews with institutional and community-level
      stakeholders of the commission. RESULTS: The lack of clear guidelines and
      regulations means that the stakeholders own motivations, agendas and power
      resources play an important part in defining the roles of the participants.
      Institutional stakeholders have the human and financial power to make policies.
      The community-level stakeholders are token participants with little power
      resources. Their main role is to identify the needs of their communities and seek
      help from the authorities. Satisfaction and the perceived benefits that the
      stakeholders obtain from the process play an important part in maintaining the
      commission's dynamic, which is unlikely to change unless the stakeholders
      perceive that the benefit they obtain does not outweigh the effort their role
      entails. CONCLUSION: Without more uniformed mechanisms and incentives for
      municipalities to work towards the national goal of equitable involvement in the
      development process, the achievements will be fragmented and will depend on the
      individual stakeholder's good will.

PMID- 21902776
TI  - Music as a nursing intervention: effects of music listening on blood pressure,
      heart rate, and respiratory rate in abdominal surgery patients.
AB  - Contradictory results have been presented on how music listening affects
      patients' blood pressure, heart rate, and respiratory rate. The aim of the
      present study was to evaluate the effects of music listening on blood pressure,
      heart rate, and respiratory rate on operation day, and on the first, second, and
      third postoperative days in abdominal surgery patients. Using a quasi
      experimental pretest-post-test design, 168 abdominal surgery patients were
      assigned every second week to the music group (n=83) or to the control group
      (n=85) for 25 months. In the music group, the respiratory rate was significantly
      lower after intervention on both the first and second postoperative days compared
      with the control group. A significant reduction in systolic blood pressure was
      demonstrated in the group that received music compared with the control group on
      both the first and second postoperative days. Evaluation of the long-term effects
      of music on physiological factors showed that the respiratory rate in the music
      group was significantly lower compared with the control group. Nurses should
      offer music listening to surgery patients because of its potential benefit.

PMID- 21902775
TI  - HIV-1 Vpu antagonizes BST-2 by interfering mainly with the trafficking of newly
      synthesized BST-2 to the cell surface.
AB  - Bone marrow stromal cell antigen-2 (BST-2) inhibits human immunodeficiency virus
      type 1 (HIV-1) release by cross-linking nascent virions on infected cell surface.
      HIV-1 Vpu is thought to antagonize BST-2 by downregulating its surface levels via
      a mechanism that involves intracellular sequestration and lysosomal degradation.
      Here, we investigated the functional importance of cell-surface BST-2
      downregulation and the BST-2 pools targeted by Vpu using an inducible proviral
      expression system. Vpu established a surface BST-2 equilibrium at ~60% of its
      initial levels within 6 h, a condition that coincided with detection of viral
      release. Analysis of BST-2 post-endocytic trafficking revealed that the protein
      is engaged in a late endosomal pathway independent of Vpu. While Vpu moderately
      enhanced cell-surface BST-2 clearance, it strongly affected the protein resupply
      to the plasma membrane via newly synthesized proteins. Noticeably, Vpu affected
      clearance of surface BST-2 more substantially in Jurkat T cells than in HeLa
      cells, suggesting a cell-dependent impact of Vpu on the pool of surface BST-2.
      Collectively, our data reveal that Vpu imposes a new BST-2 equilibrium,
      incompatible with efficient restriction of HIV-1 release, by combining an
      acceleration of surface BST-2 natural clearance, whose degree might be cell-type
      dependent, to a severe impairment of the protein resupply to the plasma membrane.

PMID- 21902777
TI  - Attitudes, beliefs, and practices of Sri Lankan nurses toward cancer pain
      management: an ethnographic study.
AB  - Cancer pain is a serious problem that requires specialized nursing knowledge. In
      the present ethnographic study, we sought to explore the experiences and cancer
      pain management practices of nurses working at a government hospital in Sri
      Lanka. Data were collected from October 2007 to January 2008, and were obtained
      by observing the nurses in a cancer ward, conducting semistructured interviews
      with 10 participants, and maintaining a research diary. To analyze the data, the
      data were coded, and an integrative process was implemented to develop
      categories. The results suggested that Sri Lankan nurses perform poor cancer pain
      management practices due to a lack of resources, a shortage of nurses, and poor
      workload allocation within the hospital. Additionally, the nurses are not
      autonomous, and are required to refer to medical staff for cancer pain management
      strategies. The nurses work in a task-oriented system that rarely acknowledges
      cancer patients' pain management needs. This study might improve nursing pain
      management practices for cancer patients and lead to changes in the curriculum of
      nursing courses in Sri Lanka.

PMID- 21902778
TI  - Organizational features of workplace and job engagement among Swiss healthcare
      workers.
AB  - The aim of this study was to determine the engagement level among healthcare
      workers in a Swiss hospital, identifying organizational predictors that could
      affect it. A four-part survey (a demographic questionnaire, Maslach Burnout
      Inventory-General Survey, Areas of Worklife Scale, and the General Health
      Questionnaire) was completed by 206 nurses and physicians. With regards to
      organizational predictors of job engagement, energy was primarily influenced by
      workload, involvement by values, and efficacy by reward. Moreover, we found that
      engagement might affect psychophysical health conditions: better health generally
      corresponds to higher levels of engagement. These results confirm that engagement
      is influenced by organizational variables and that engaged employees are
      generally more healthy and efficient. Therefore, interventions to minimize the
      impact of work stressors and to improve engagement are needed. Effective
      management of excessive workload, higher levels of autonomy, and greater job
      support are vital to limit psychological problems of healthcare workers.

PMID- 21902779
TI  - Descemet's membrane substrate from human donor lens anterior capsule.
AB  - BACKGROUND: To study the potential use of human donor anterior lens capsule as a
      Descemet's membrane substrate. METHODS: Anterior lens capsules were recovered
      from the lenses of 30 cornea donors. Human corneal endothelial cells were
      recovered from the remaining corneal sclera rims of 15 donor corneas used for
      penetrating keratoplasty. Samples were sorted into three groups. Group 1
      consisted of 10 samples in which the endothelial cells were allowed to grow on
      anterior lens capsules. In Group 2 human corneal endothelial cells grew on a
      collagen membrane and in Group 3 on polystyrene culture plates. Cell density,
      morphology and adherence of the cell-capsule complex were evaluated at 1, 4, 7
      and 14days with a phase-contrast microscope, a scanning electron microscope and
      by histology. Cell viability was quantified by a microscopic live-dead assay.
      Expression of zonula occludens-1, Na(+) /K(+) -adenosine triphosphatase, tissue
      transglutaminase and vimentin were investigated by immunohistochemistry. RESULTS:
      A mean diameter of 10.05+/-0.13mm of anterior capsule was obtained as a substrate
      for cell culture. Endothelial cell density of Group 1 was measured at 2455.4+/
      283.8cells/mm(2) , which was also comparable with the cell density of the control
      group. Cell viability was 95% or superior in all groups and multiple cellular
      interconnections developed between growing cells. Immunohistochemical analysis
      demonstrated strongly positive staining for all investigated proteins. Electron
      microscopy confirmed the adherence and monolayer growth of the endothelial cells.
      CONCLUSIONS: Human donor anterior lens capsule might therefore be a potential
      scaffold for the ex vivo expansion of human corneal endothelial cells.

PMID- 21902780
TI  - Ocular infections caused by non-tuberculous mycobacteria: update on epidemiology
      and management.
AB  - BACKGROUND:   To provide an update on the frequency, distribution, risk factors
      and in vitro susceptibility of ocular infections caused by non-tuberculous
      mycobacteria. DESIGN:   Retrospective study of university clinic patients.
      PARTICIPANTS:   One hundred thirty-nine patients with culture confirmed non
      tuberculous mycobacteria infections seen at Bascom Palmer Eye Institute from
      January 1980 to July 2007. METHODS:   Chart review of data collected included
      patients' demographics, risk factors, microbiological profiles and clinical
      outcomes. MAIN OUTCOME MEASURES:   Frequency, distribution, risk factors and in
      vitro susceptibility of ocular infections caused by non-tuberculous mycobacteria.
      RESULTS:   A total of 183 non-tuberculous mycobacteria isolates from 142 eyes
      were identified, with a fourfold increase in the number of eyes infected with non
      tuberculous mycobacteria from 1980-1989 (13.4%) to 2000-2007 (56.3%). Eighty
      three percent of non-tuberculous mycobacteria isolates were identified as M.
      abscessus/chelonae. The majority (91%) of isolates were recovered within 10 days.
      Common diagnoses included keratitis (36.6%), scleral buckle infections (14.8%)
      and socket/implant infections (14.8%). Identifiable risk factors were presence of
      biomaterials (63.1%), ocular surgery (24.1%) and steroid exposure (77%). The
      median time from diagnosis of culture positive non-tuberculous mycobacteria
      infection to resolution was 13 to 24 weeks. Combination therapy was used to treat
      80% of infected eyes. In vitro susceptibility of non-tuberculous mycobacteria
      isolates were: amikacin, 81%; clarithromycin, 93%; and moxifloxacin, 21%.
      CONCLUSIONS:   The incidence of ocular infections caused by non-tuberculous
      mycobacteria has increased within the last 8 years, with a high number of
      biomaterial associated infections among this group. Clinical diagnosis and
      microbiological confirmation of non-tuberculous mycobacteria infections remains
      challenging. Patient outcomes may be improved by early diagnosis, appropriate
      therapy and removal of biomaterials.

PMID- 21902781
TI  - Examination of the performance of different pointwise linear regression
      progression criteria to detect glaucomatous visual field change.
AB  - BACKGROUND: We aimed to investigate the performance of five different trend
      analysis criteria for the detection of glaucomatous progression and to determine
      the most frequently and rapidly progressing locations of the visual field.
      DESIGN: Retrospective cohort. PARTICIPANTS OR SAMPLES: Treated glaucoma patients
      with >= 8 Swedish Interactive Thresholding Algorithm (SITA)-standard 24-2 visual
      field tests. METHODS: Progression was determined using trend analysis. Five
      different criteria were used: (A) >= 1 significantly progressing point; (B) >= 2
      significantly progressing points; (C) >= 2 progressing points located in the same
      hemifield; (D) at least two adjacent progressing points located in the same
      hemifield; (E) >= 2 progressing points in the same Garway-Heath map sector. MAIN
      OUTCOME MEASURES: Number of progressing eyes and false-positive results. RESULTS:
      We included 587 patients. The number of eyes reaching a progression end-point
      using each criterion was: A = 300 (51%); B = 212 (36%); C = 194 (33%); D = 170
      (29%); and E = 186 (31%) (P <= 0.03). The numbers of eyes with positive slopes
      were: A = 13 (4.3%); B = 3 (1.4%); C = 3 (1.5%); D = 2 (1.1%); and E = 3 (1.6%)
      (P = 0.06). The global slopes for progressing eyes were more negative in Groups
      B, C and D than in Group A (P = 0.004). The visual field locations that
      progressed more often were those in the nasal field adjacent to the horizontal
      midline. CONCLUSIONS: Pointwise linear regression criteria that take into account
      the retinal nerve fibre layer anatomy enhances the specificity of trend analysis
      for the detection glaucomatous visual field progression.

PMID- 21902782
TI  - Trends in the distribution of donor corneal tissue and indications for corneal
      transplantation: the New Zealand National Eye Bank Study 2000-2009.
AB  - BACKGROUND: To investigate the indications for corneal transplantation and the
      distribution of donor corneal tissue in New Zealand. DESIGN: Analysis of the
      prospective database of the New Zealand National Eye Bank. PARTICIPANTS: A total
      of 2205 corneal transplants were assessed. METHODS: New Zealand National Eye Bank
      records were analysed for the decade 2000-2009. MAIN OUTCOME MEASURES: Variables
      analysed included donor corneal tissue distribution (including public and private
      sectors), indications for transplantation, donor corneal tissue recipient
      demographics (age and gender) and corneal transplantation type. RESULTS: An
      average of 220 corneal transplants were performed each year over the 10-year
      period (n=2205). The median recipient age was 45years (range 3 to 102years) and
      54.0% of recipients were male. In total 71.8% of transplants were performed in
      the public health sector. Surgeons in the Auckland metropolitan area performed
      47.2% of all corneal transplants. The most common indications for corneal
      transplantation were: keratoconus (41.1%), repeat transplant (17.0%),
      aphakic/pseudophakic bullous keratopathy (13.9%), corneal dystrophy (10.7%),
      keratitis (7.9%) and trauma (3.7%). Overall, penetrating keratoplasty accounted
      for 90.7% of all corneal transplants, however, during the latter half of the
      study there was a progressive shift in transplantation type, with deep anterior
      lamellar keratoplasty and Descemet's stripping endothelial keratoplasty combined
      accounting for 32.3% of all transplants in the final year of the study period.
      CONCLUSIONS: This New Zealand National Eye Bank study provides valuable data
      regarding the indications for corneal transplantation, transplant recipient
      demographics and changes in transplantation type in New Zealand over the past
      decade.

PMID- 21902783
TI  - Prevalence of blindness and low vision: a study in the rural Heilongjiang
      Province of China.
AB  - BACKGROUND:   The prevalence of blind individuals in the north of China is
      unknown. The study aimed to investigate the prevalence and causes of blindness
      and low vision in rural areas in Heilongjiang province of China in 2008-2009.
      DESIGN:   Cross-sectional study. PARTICIPANTS OR SAMPLES:   A cluster random
      sampling method was used to recruit participants of all ages in rural areas of
      Heilongjiang. METHODS:   Trained professionals performed interviews and clinical
      examinations to measure visual acuity. The relationships between blindness or low
      vision and age, gender and education level were analysed. MAIN OUTCOME MEASURES: 
      The main outcome measure was prevalence rates of bilateral blindness and
      bilateral low vision. RESULTS:   Of the 11 787 subjects, 10 384 (88.1%) were
      surveyed. The overall age-adjusted prevalence rates were 0.7% (95% confidence
      interval: 0.5-0.8%) for bilateral blindness and 1.7% (95% confidence interval:
      1.4-1.9%) for bilateral low vision. The prevalence rates of blindness and low
      vision were higher in the elderly and uneducated population (P < 0.05). The main
      causes for blindness and low vision were cataracts (44.1 and 46.0%, respectively)
      and refractive errors (17.7 and 42.5%, respectively). CONCLUSION:   Blindness and
      low vision are highly prevalent among people with cataracts and refractive
      errors. Eye care planning must focus on treating the avoidable and curable forms
      of blindness.

PMID- 21902784
TI  - Insulin-like growth factor-2 antisense oligonucleotides inhibits myopia by
      expression blocking of retinal insulin-like growth factor-2 in guinea pig.
AB  - OBJECTIVE:   To clarify the role of IGF-2 on the development of myopia, the
      dynamic expression of IGF-2 was investigated in the FD eyes' retina, and the
      effects of intravitreous injection with IGF-2 ASON was studied on the diopter and
      axial eye length of FD eyes. METHODS:   64 guinea pigs were divided into 2
      groups. In group A (n = 24), the right eyes were covered. On days 7, 14 and 21,
      the diopter, axial eye length and level of IGF-2 of both eyes were measured in
      every 8 guinea pigs. In group B (n = 40), the right eyes were covered. On day 1,
      the right eyes were received intravitreal injection with 40 ug IGF-2SON, 10 ug,
      20 ug or 40 ug IGF-2 ASON. The diopter, axial eye length and level of IGF-2 were
      measured on day 14. RESULTS:   FD eyes showed myopic shift, axial length
      enlongation, and up-regulation in retinal IGF-2 from day 7 to day 21. The level
      of retinal IGF-2 in FD eyes was higher than that in non-FD eyes. Compare with FD
      eyes without injection, the myopia diopter of FD eyes decreased in received
      intravitreous injection with IGF-2 ASON, axial length shortened, and down
      regulated with retinal IGF-2. With the increase dose of IGF-2 ASON, the change of
      myopic diopter, axial length, and level of retinal IGF-2 were showed more and
      more significant. CONCLUSIONS:   FD is effective to up-regulate the level of
      retinal IGF-2 expression in guinea pig. Intravitreous injection with IGF-2 ASON
      can inhibit the development of myopia.

PMID- 21902785
TI  - Anti-vascular endothelial growth factor for myopic choroidal neovascularization.
AB  - Myopic choroidal neovascularization (CNV) is a vision-threatening complication in
      the eyes with pathological myopia, which is particularly prevalent among young
      and middle-aged Asians globally. To date, the verteporfin in photodynamic therapy
      study is the only randomized-controlled study in treatment of subfoveal myopic
      CNV. However, its long-term benefit is controversial. Recently, intravitreal
      injections of anti-vascular endothelial growth factors have shown promising
      results. In the absence of randomized-controlled trial comparing the efficacy of
      anti-vascular endothelial growth factors with photodynamic therapy and placebo,
      the purpose of this article is to review the current studies on functional and
      anatomical outcomes in both subfoveal and juxtafoveal myopic CNV. Furthermore,
      the influences of various doses and frequencies, as well as age and previous
      photodynamic therapy treatment on its effect are described.

PMID- 21902786
TI  - Effect of lipoic acid on expression of angiogenic factors in diabetic rat retina.
AB  - BACKGROUND: This study evaluated the effect of a lipoic acid on reactive oxygen
      species formation and the simultaneous changes of several angiogenic factors in
      an experimental diabetic rat retina. METHODS: Diabetes was induced chemically by
      intraperitoneal injection of streptozotocin in 30 Sprague-Dawley rats. After
      inducing diabetes, lipoic acid (10 mg/kg) was administered to 10 rats orally. The
      rats were divided into normal, diabetes mellitus, and lipoic acid-treated groups
      (each group n = 10). The eyeballs were harvested 8 weeks after inducing diabetes.
      The expression of vascular endothelial growth factor, erythropoietin,
      angiopoietin 1 and 2 and NADPH oxidase was examined in the rat retina using
      reverse transcription-polymerase chain reaction and Western blot. Superoxide
      formation was examined using dihydroethidium stain. RESULTS: Dihydroethidium
      analyses showed increased superoxide formation in the retina of the diabetic
      group. The superoxide formation was suppressed with lipoic acid treatment.
      Western blot analysis showed that NADPH oxidase was decreased in the diabetic
      group and returned to normal level in the lipoic acid-treated group. Treatment
      with lipoic acid blocked hyperglycaemia induced increases of vascular endothelial
      growth factor, angiopoietin 2 and erythropoietin shown by reverse transcription
      polymerase chain reaction and Western blot analysis. CONCLUSIONS: Lipoic acid
      treatment suppressed expression of vascular endothelial growth factor,
      angiopoietin 2 and erythropoietin via blockade of superoxide formation.
      Antioxidant treatment is suspected to have an antiangiogenic effect.

PMID- 21902787
TI  - Prevalence of pseudoexfoliation syndrome in indigenous Australians within central
      Australia: The Central Australian Ocular Health Study.
AB  - BACKGROUND:   Pseudoexfoliation syndrome (XFS) has been found to occur more
      commonly among indigenous Australians. This paper was designed to determine the
      prevalence of XFS within the indigenous Australian population living in central
      Australia. DESIGN:   Clinic-based cross-sectional study. PARTICIPANTS:   One
      thousand eight hundred eighty-four individuals living in one of 30 remote
      communities within the statistical local area of 'Central Australia' were
      recruited. This equated to 36% of those aged 20 years or older and 67% of those
      aged 40 years or older within this district. METHODS:   Participants aged 20
      years or over were recruited as they presented to the eye clinic at each remote
      community. Slit-lamp examination was performed, and the presence of XFS in each
      eye was recorded and presented. MAIN OUTCOME MEASURE:   Prevalence and
      associations of XFS. RESULTS:   XFS was present in one or both eyes of 4.7% of
      the individuals recruited into the study. Prevalence increased with age (5.9% of
      those >=40 years and 12.7% >= 60 years). There was a significant association
      between the presence of XFS and climatic keratopathy (chi(2)  = 240.13; P <
      0.00001). Notably, none of those with XFS had ocular hypertension or glaucoma.
      CONCLUSION:   XFS was present in a significantly higher proportion of indigenous
      Australians compared with previously reported prevalence estimates among non
      indigenous Australians. The association found between XFS and climatic
      keratopathy may represent a common causal link between the two conditions. The
      lack of association of XFS with ocular hypertension and glaucoma appears to be a
      unique feature of the indigenous Australian population, and this merits further
      investigation.

PMID- 21902788
TI  - Methodology and early findings of the Diabetes Management Project: a cohort study
      investigating the barriers to optimal diabetes care in diabetic patients with and
      without diabetic retinopathy.
AB  - BACKGROUND: The Diabetes Management Project is investigating the clinical,
      behavioural and psychosocial barriers to optimal diabetes care in individuals
      with and without diabetic retinopathy. DESIGN: Prospective cohort. PARTICIPANTS:
      Two hundred and twenty-three and 374 patients without and with diabetic
      retinopathy, respectively. METHODS: All individuals underwent a comprehensive
      dilated eye test, anthropometric measurements, blood and urine samples, and
      psychosocial questionnaires. MAIN OUTCOME MEASURES: Good glycaemic control was
      defined as glycosylated haemoglobin < 7%, good blood pressure control as systolic
      and diastolic values <=130 and 80 mmHg, respectively, and good diabetes control
      as glycosylated haemoglobin < 7% and blood pressure values <=130 and 80 mmHg.
      RESULTS: Four hundred and one males (65.4%) and 212 females (34.6%) aged 26-90
      years (mean age +/- standard deviation = 64.6 +/- 11.6) were examined. The median
      glycosylated haemoglobin for all participants was 7.5% (interquartile range =
      1.7%). Average systolic and diastolic blood pressure values were 139.7 mmHg
      (standard deviation = 18.8) and 92.7 mmHg (standard deviation = 30.9),
      respectively. Initial data analyses indicate that over two-thirds of participants
      with diabetes have poor glycaemic control, which was worse in those with diabetic
      retinopathy compared with those without (76.3% vs. 49.3%; P < 0.001). Blood
      pressure control was similar for those with and without diabetic retinopathy,
      with almost a third (28.5%) of the total sample having poor blood pressure
      control. Overall, those with diabetic retinopathy had poorer diabetes control
      than those without (24.3% vs. 13.7%; P = 0.002). CONCLUSIONS: Our findings
      substantiate the implementation of the Diabetes Management Project, developed to
      assess factors associated with suboptimal diabetes care.

PMID- 21902789
TI  - Intrastromal corneal ring segments: visual outcomes from a large case series.
AB  - BACKGROUND:   To evaluate the clinical safety and efficacy of implanted Ferrara
      intrastromal corneal ring segments in a large sample of patients with ectatic
      corneal disease. DESIGN:   Retrospective, consecutive case series. SAMPLES:   A
      total of 1073 eyes of 810 patients consecutively operated from January 2006 to
      July 2008 were evaluated. METHODS:   Two groups were created according to the
      type of ring implanted: Group 1 - patients implanted with the 160 degrees  of arc
      ring - and Group 2 - patients implanted with the 210 degrees  of arc ring. MAIN
      OUTCOME MEASURES:   Uncorrected visual acuity, best-corrected visual acuity,
      keratometry, asphericity and pachymetry at the thinnest point of the cornea. All
      patients were evaluated using a corneal tomography (Pentacam, Oculus, Inc.,
      Lynnwood, WA, USA). RESULTS:   For Group 1 patients, uncorrected visual acuity
      increased to 20/80, best-corrected visual acuity increased to 20/40, asphericity
      decreased to -0.35, spherical equivalent decreased to -2.26 D and keratometry
      decreased to 45.72 D (P < 0.001 for each compared with preoperative values). For
      Group 2 patients, uncorrected visual acuity increased to 20/130, best-corrected
      visual acuity increased to 20/60, asphericity decreased to -0.56, spherical
      equivalent decreased to -4.14 D and keratometry decreased to 48.10 D (P < 0.001
      for each compared with preoperative values). The 210 degrees  intrastromal
      corneal ring segments reduced keratometry and asphericity more than the 160
      degrees  intrastromal corneal ring segments did. The complication rate was 3.82%.
      CONCLUSIONS:   Ferrara intrastromal corneal ring segments implantation is safe
      and effective and has a low complication rate. It can effectively reduce the
      corneal steepening and improve uncorrected visual acuity and best-corrected
      visual acuity in patients with keratoconus.

PMID- 21902790
TI  - Scanning laser ophthalmoscope retro-mode imaging of foveal schisis in eyes with X
      linked retinoschisis.

PMID- 21902791
TI  - Pharmaceutical advertising in ophthalmology.

PMID- 21902792
TI  - The Eye Institute of Thrace glaucoma progression diagram (EIT-GPD): incorporating
      the relationship between visual ability and visual fields.

PMID- 21902793
TI  - Carnitine palmitoyl transferase II deficiency: a possible association with
      progression of normal pressure glaucoma.

PMID- 21902794
TI  - Expression of biomineralization-related ion transport genes in Emiliania huxleyi.
AB  - Biomineralization in the marine phytoplankton Emiliania huxleyi is a stringently
      controlled intracellular process. The molecular basis of coccolith production is
      still relatively unknown although its importance in global biogeochemical cycles
      and varying sensitivity to increased pCO2 levels has been well documented. This
      study looks into the role of several candidate Ca2+, H+ and inorganic carbon
      transport genes in E. huxleyi, using quantitative reverse transcriptase PCR.
      Differential gene expression analysis was investigated in two isogenic pairs of
      calcifying and non-calcifying strains of E. huxleyi and cultures grown at various
      Ca2+ concentrations to alter calcite production. We show that calcification
      correlated to the consistent upregulation of a putative HCO3- transporter
      belonging to the solute carrier 4 (SLC4) family, a Ca2+/H+ exchanger belonging to
      the CAX family of exchangers and a vacuolar H+-ATPase. We also show that the
      coccolith-associated protein, GPA is downregulated in calcifying cells. The data
      provide strong evidence that these genes play key roles in E. huxleyi
      biomineralization. Based on the gene expression data and the current literature a
      working model for biomineralization-related ion transport in coccolithophores is
      presented.

PMID- 21902795
TI  - Francisella infection triggers activation of the AIM2 inflammasome in murine
      dendritic cells.
AB  - The intracellular bacterium Francisella tularensis is the causative agent of
      tularemia, a potentially fatal disease. In macrophages, Francisella escapes the
      initial phagosome and replicates in the cytosol, where it is detected by the
      cytosolic DNA sensor AIM2 leading to activation of the AIM2 inflammasome.
      However, during aerosol infection, Francisella is also taken up by dendritic
      cells. In this study, we show that Francisella novicida escapes into the cytosol
      of bone marrow-derived dendritic cells (BMDC) where it undergoes rapid
      replication. We show that F. novicida activates the AIM2 inflammasome in BMDC,
      causing release of large amounts of IL-1beta and rapid host cell death. The
      Francisella Pathogenicity Island is required for bacterial escape and replication
      and for inflammasome activation in dendritic cells. In addition, we show that
      bacterial DNA is bound by AIM2, which leads to inflammasome assembly in infected
      dendritic cells. IFN-beta is upregulated in BMDC following Francisella infection,
      and the IFN-beta signalling pathway is partially required for inflammasome
      activation in this cell type. Taken together, our results demonstrate that F.
      novicida induces inflammasome activation in dendritic cells. The resulting
      inflammatory cell death may be beneficial to remove the bacterial replicative
      niche and protect the host.

PMID- 21902797
TI  - Ultra-low gossypol cottonseed: generational stability of the seed-specific, RNAi
      mediated phenotype and resumption of terpenoid profile following seed
      germination.
AB  - Cottonseed, containing 22.5% protein, remains an under-utilized and under-valued
      resource because of the presence of toxic gossypol. RNAi-knockdown of delta
      cadinene synthase gene(s) was used to engineer plants that produced ultra-low
      gossypol cottonseed (ULGCS). In the original study, we observed that RNAi plants,
      a month or older, maintain normal complement of gossypol and related terpenoids
      in the roots, foliage, floral organs, and young bolls. However, the terpenoid
      levels and profile of the RNAi lines during the early stages of germination,
      under normal conditions and in response to pathogen exposure, had not been
      examined. Results obtained in this study show that during the early stages of
      seed germination/seedling growth, in both non-transgenic and RNAi lines, the
      tissues derived directly from bulk of the seed kernel (cotyledon and hypocotyl)
      synthesize little, if any new terpenoids. However, the growing root tissue and
      the emerging true leaves of RNAi seedlings showed normal, wild-type terpenoid
      levels. Biochemical and molecular analyses showed that pathogen-challenged parts
      of RNAi seedlings are capable of launching a terpenoid-based defence response.
      Nine different RNAi lines were monitored for five generations. The results show
      that, unlike the unstable nature of antisense-mediated low seed-gossypol
      phenotype, the RNAi-mediated ULGCS trait exhibited multi-generational stability.

PMID- 21902798
TI  - The role of Delta6-desaturase acyl-carrier specificity in the efficient synthesis
      of long-chain polyunsaturated fatty acids in transgenic plants.
AB  - The role of acyl-CoA-dependent Delta6-desaturation in the heterologous synthesis
      of omega-3 long-chain polyunsaturated fatty acids was systematically evaluated in
      transgenic yeast and Arabidopsis thaliana. The acyl-CoA Delta6-desaturase from
      the picoalga Ostreococcus tauri and orthologous activities from mouse (Mus
      musculus) and salmon (Salmo salar) were shown to generate substantial levels of
      Delta6-desaturated acyl-CoAs, in contrast to the phospholipid-dependent Delta6
      desaturases from higher plants that failed to modify this metabolic pool.
      Transgenic plants expressing the acyl-CoA Delta6-desaturases from either O. tauri
      or salmon, in conjunction with the two additional activities required for the
      synthesis of C20 polyunsaturated fatty acids, contained higher levels of
      eicosapentaenoic acid compared with plants expressing the borage phospholipid
      dependent Delta6-desaturase. The use of acyl-CoA-dependent Delta6-desaturases
      almost completely abolished the accumulation of unwanted biosynthetic
      intermediates such as gamma-linolenic acid in total seed lipids. Expression of
      acyl-CoA Delta6-desaturases resulted in increased distribution of long-chain
      polyunsaturated fatty acids in the polar lipids of transgenic plants, reflecting
      the larger substrate pool available for acylation by enzymes of the Kennedy
      pathway. Expression of the O. tauriDelta6-desaturase in transgenic Camelina
      sativa plants also resulted in the accumulation of high levels of Delta6
      desaturated fatty acids. This study provides evidence for the efficacy of using
      acyl-CoA-dependent Delta6-desaturases in the efficient metabolic engineering of
      transgenic plants with high value traits such as the synthesis of omega-3 LC
      PUFAs.

PMID- 21902796
TI  - Salmonella effectors: important players modulating host cell function during
      infection.
AB  - Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative
      facultative food-borne pathogen that causes gastroenteritis in humans. This
      bacterium has evolved a sophisticated machinery to alter host cell function
      critical to its virulence capabilities. Central to S. Typhimurium pathogenesis
      are two Type III secretion systems (T3SS) encoded within pathogenicity islands
      SPI-1 and SPI-2 that are responsible for the secretion and translocation of a set
      of bacterial proteins termed effectors into host cells with the intention of
      altering host cell physiology for bacterial entry and survival. Thus, once
      delivered by the T3SS, the secreted effectors play critical roles in manipulating
      the host cell to allow for bacteria invasion, induction of inflammatory
      responses, and the assembly of an intracellular protective niche created for
      bacterial survival and replication. Emerging evidence indicates that these
      effectors are modular proteins consisting of distinct functional domains/motifs
      that are utilized by the bacteria to activate intracellular signalling pathways
      modifying host cell function. Also, recently reported are the dual functionality
      of secreted effectors and the concept of 'terminal reassortment'. Herein, we
      highlight some of the nascent concepts regarding Salmonella effectors in the
      context of infection.

PMID- 21902799
TI  - In planta production of the highly potent resveratrol analogue pterostilbene via
      stilbene synthase and O-methyltransferase co-expression.
AB  - Resveratrol and related stilbenes are thought to play important roles in defence
      responses in several plant species and have also generated considerable interest
      as nutraceuticals owing to their diverse health-promoting properties.
      Pterostilbene, a 3,5-dimethylether derivative of resveratrol, possesses
      properties similar to its parent compound and, additionally, exhibits
      significantly higher fungicidal activity in vitro and superior pharmacokinetic
      properties in vivo. Recombinant enzyme studies carried out using a previously
      characterized O-methyltransferase sequence from Sorghum bicolor (SbOMT3)
      demonstrated its ability to catalyse the A ring-specific 3,5-bis-O-methylation of
      resveratrol, yielding pterostilbene. A binary vector was constructed for the
      constitutive co-expression of SbOMT3 with a stilbene synthase sequence from
      peanut (AhSTS3) and used for the generation of stably transformed tobacco and
      Arabidopsis plants, resulting in the accumulation of pterostilbene in both
      species. A reduced floral pigmentation phenotype observed in multiple tobacco
      transformants was further investigated by reversed-phase HPLC analysis, revealing
      substantial decreases in both dihydroquercetin-derived flavonoids and
      phenylpropanoid-conjugated polyamines in pterostilbene-producing SbOMT3/AhSTS3
      events. These results demonstrate the potential utility of this strategy for the
      generation of pterostilbene-producing crops and also underscore the need for the
      development of additional approaches for minimizing concomitant reductions in key
      phenylpropanoid-derived metabolites.

PMID- 21902801
TI  - Sex differences in telomeres and lifespan.
AB  - Males and females often age at different rates resulting in longevity 'gender
      gaps', where one sex outlives the other. Why the sexes have different lifespans
      is an age-old question, still fiercely debated today. One cellular process
      related to lifespan, which is known to differ according to sex, is the rate at
      which the protective telomere chromosome caps are lost. In humans, men have
      shorter lifespans and greater telomere shortening. This has led to speculation in
      the medical literature that sex-specific telomere shortening is one cause of sex
      specific mortality. However, telomere shortening may be a cause for and/or a
      consequence of the processes that govern survival, and to infer general
      principles from single-taxon studies may be misleading. Here, we review recent
      work on telomeres in a variety of animal taxa, including those with reverse
      sexual lifespan dimorphism (i.e., where males live longer), to establish whether
      sex-specific survival is generally associated with sex differences in telomere
      dynamics. By doing this, we attempt to tease apart the potential underlying
      causes for sex differences in telomere lengths in humans and highlight targets
      for future research across all taxa.

PMID- 21902800
TI  - Neuroimaging and obesity: current knowledge and future directions.
AB  - Neuroimaging is becoming increasingly common in obesity research as investigators
      try to understand the neurological underpinnings of appetite and body weight in
      humans. Positron emission tomography (PET), functional magnetic resonance imaging
      (fMRI) and magnetic resonance imaging (MRI) studies examining responses to food
      intake and food cues, dopamine function and brain volume in lean vs. obese
      individuals are now beginning to coalesce in identifying irregularities in a
      range of regions implicated in reward (e.g. striatum, orbitofrontal cortex,
      insula), emotion and memory (e.g. amygdala, hippocampus), homeostatic regulation
      of intake (e.g. hypothalamus), sensory and motor processing (e.g. insula,
      precentral gyrus), and cognitive control and attention (e.g. prefrontal cortex,
      cingulate). Studies of weight change in children and adolescents, and those at
      high genetic risk for obesity, promise to illuminate causal processes. Studies
      examining specific eating behaviours (e.g. external eating, emotional eating,
      dietary restraint) are teaching us about the distinct neural networks that drive
      components of appetite, and contribute to the phenotype of body weight. Finally,
      innovative investigations of appetite-related hormones, including studies of
      abnormalities (e.g. leptin deficiency) and interventions (e.g. leptin
      replacement, bariatric surgery), are shedding light on the interactive
      relationship between gut and brain. The dynamic distributed vulnerability model
      of eating behaviour in obesity that we propose has scientific and practical
      implications.

PMID- 21902802
TI  - Sir2 deletion prevents lifespan extension in 32 long-lived mutants.
AB  - Activation of Sir2 orthologs is proposed to increase lifespan downstream of
      dietary restriction. Here, we describe an examination of the effect of 32
      different lifespan-extending mutations and four methods of DR on replicative
      lifespan (RLS) in the short-lived sir2Delta yeast strain. In every case, deletion
      of SIR2 prevented RLS extension; however, RLS extension was restored when both
      SIR2 and FOB1 were deleted in several cases, demonstrating that SIR2 is not
      directly required for RLS extension. These findings indicate that suppression of
      the sir2Delta lifespan defect is a rare phenotype among longevity interventions
      and suggest that sir2Delta cells senesce rapidly by a mechanism distinct from
      that of wild-type cells. They also demonstrate that failure to observe lifespan
      extension in a short-lived background, such as cells or animals lacking sirtuins,
      should be interpreted with caution.

PMID- 21902803
TI  - Stem cell depletion in Hutchinson-Gilford progeria syndrome.
AB  - Hutchinson-Gilford progeria syndrome (HGPS or progeria) is a very rare genetic
      disorder with clinical features suggestive of premature aging. Here, we show that
      induced expression of the most common HGPS mutation (LMNA c.1824C>T, p.G608G)
      results in a decreased epidermal population of adult stem cells and impaired
      wound healing in mice. Isolation and growth of primary keratinocytes from these
      mice demonstrated a reduced proliferative potential and ability to form colonies.
      Downregulation of the epidermal stem cell maintenance protein p63 with
      accompanying activation of DNA repair and premature senescence was the probable
      cause of this loss of adult stem cells. Additionally, upregulation of multiple
      genes in major inflammatory pathways indicated an activated inflammatory
      response. This response has also been associated with normal aging, emphasizing
      the importance of studying progeria to increase the understanding of the normal
      aging process.

PMID- 21902804
TI  - Petal Development in Lotus japonicus.
AB  - Previous studies have demonstrated that petal shape and size in legume flowers
      are determined by two separate mechanisms, dorsoventral (DV) and organ internal
      (IN) asymmetric mechanisms, respectively. However, little is known about the
      molecular mechanisms controlling petal development in legumes. To address this
      question, we investigated petal development along the floral DV axis in Lotus
      japonicus with respect to cell and developmental biology by comparing wild-type
      legumes to mutants. Based on morphological markers, the entire course of petal
      development, from initiation to maturity, was grouped to define 3 phases or 13
      stages. In terms of epidermal micromorphology from adaxial surface, mature petals
      were divided into several distinct domains, and characteristic epidermal cells of
      each petal differentiated at stage 9, while epidermal cells of all domains were
      observed until stage 12. TCP and MIXTA-like genes were found to be differentially
      expressed in various domains of petals at stages 9 and 12. Our results suggest
      that DV and IN mechanisms interplay at different stages of petal development, and
      their interaction at the cellular and molecular level guides the elaboration of
      domains within petals to achieve their ideal shape, and further suggest that TCP
      genes determine petal identity along the DV axis by regulating MIXTA-like gene
      expression. 

PMID- 21902805
TI  - The scandal of unpublished research.

PMID- 21902806
TI  - ESPGHAN's 2008 recommendation for early introduction of complementary foods: how
      good is the evidence?
AB  - Since 2002, the World Health Organization and many governments and professional
      associations have recommended exclusive breastfeeding for 6 months followed by
      complementary feeding (giving solid foods alongside breast milk) as optimal
      infant feeding practice. Several articles have been published challenging this
      recommendation. Arguably, the most influential has been the 2008 commentary of
      the European Society for Pediatric Gastroenterology, Hepatology and Nutrition
      (ESPGHAN) Committee on Nutrition, which recommended that complementary foods
      should be introduced to all infants between 17 and 26 weeks. We challenge the
      validity of ESPGHAN's position, questioning the adequacy of the literature
      search, the interpretation and evidence used to reach their conclusions and the
      balance of an approach that focuses on disease prevention, with scant
      consideration of growth and neuromotor development. We contend that ESPGHAN's
      position should be understood as an expert opinion that may be influenced by
      conflicts of interest. In our view, the ESPGHAN position paper is not evidence
      based and does not justify a change of the current public health recommendation
      for 6 months of exclusive breastfeeding. At an individual level, health
      professionals should understand that developmental readiness for starting solid
      foods has an age range like other developmental milestones; that fewer infants
      will probably be ready to start complementary feeding before, rather than after,
      6 months; and that their role is to equip parents with the confidence and skills
      to recognise the signs of developmental readiness. This empowerment process for
      infants and parents should be preferred over the prescriptive ESPGHAN approach.

PMID- 21902807
TI  - Impact of early and concurrent stunting on cognition.
AB  - Undernutrition is associated with poor cognitive development, late entry into
      school, decreased years of schooling, reduced productivity and smaller adult
      stature. We use longitudinal data from 1674 Peruvian children participating in
      the Young Lives study to assess the relative impact of early stunting (stunted at
      6-18 months of age) and concurrent stunting (stunted at 4.5-6 years of age) on
      cognitive ability. Anthropometric data were longitudinally collected for children
      at 6-18 months of age and 4.5-6 years of age at which time verbal and
      quantitative ability were also assessed. We estimate that an increase in
      concurrent height-for-age z-scores (HAZ) by one standard deviation was associated
      with an increase in a child's score on the Peabody Picture Vocabulary Test (PPVT)
      by 2.35 points [confidence interval (CI): 1.55-3.15] and a 0.16 point increase on
      the cognitive development assessment (CDA) (CI: 0.05-0.27). Furthermore, we
      report that the estimate for concurrent HAZ and PPVT is significantly higher than
      the estimate for early stunting and PPVT. We found no significant difference
      between early and concurrent estimates for HAZ and CDA. Children from older
      mothers, children whose mothers had higher education levels, children living in
      urban areas, children who attended pre-school, children with fewer siblings and
      children from wealthier backgrounds scored higher on both assessments. Cognitive
      skills of children entering school were associated with early stunting but the
      strongest association was found with concurrent stunting suggesting that
      interventions preventing linear growth faltering should not only focus on the
      under 2s but include children up to 5 years of age.

PMID- 21902808
TI  - Beverage consumption and anthropometric outcomes among schoolchildren in
      Guatemala.
AB  - This analysis explores the clustering of beverage patterns in a single day in
      private vs. public school children in urban Guatemala. This study is based on
      measurements taken from 356 third- and fourth-grade pupils from the highland city
      of Quetzaltenango. Height, weight and body mass index were assessed, and one
      day's intake of all foods and beverages using a pictorial workbook and dietician
      assisted recall. Mean differences in beverage consumption were compared for
      private vs. public school children and by anthropometric outcomes (stunting,
      overweight and obesity). Plain water was consumed by 30.9% of the children on the
      day intakes were measured, with higher proportions of water drinkers among
      private school children. Children having reported water intake on that day
      consumed 154 fewer kcal (-7.7%) compared with the energy intake of children not
      having reported water intake (P = 0.02). Significantly more children of high
      socio-economic status (SES) consumed dairy, fruit juice, commercial fruit juice,
      fruit drink and soda whereas low SES children consumed thin gruels and infusions.
      A key result from this study is the finding of a lower energy intake shown by
      children reporting water intake.

PMID- 21902809
TI  - Protein transamidation by transglutaminase 2 in cells: a disputed Ca2+-dependent
      action of a multifunctional protein.
AB  - Transglutaminase 2 (TG2) is the first described cellular member of an enzyme
      family catalyzing Ca(2+)-dependent transamidation of proteins. During the last
      two decades its additional enzymatic (GTP binding and hydrolysis, protein
      disulfide isomerase, protein kinase) and non-enzymatic (multiple interactions in
      protein scaffolds) activities, which do not require Ca(2+) , have been
      recognized. It became a prevailing view that TG2 is silent as a transamidase,
      except in extreme stress conditions, in the intracellular environment
      characterized by low Ca(2+) and high GTP concentrations. To counter this
      presumption a critical review of the experimental evidence supporting the role of
      this enzymatic activity in cellular processes is provided. It includes the
      structural basis of TG2 regulation through non-canonical Ca(2+) binding sites,
      mechanisms making it sensitive to low Ca(2+) concentrations, techniques developed
      for the detection of protein transamidation in cells and examples of basic
      cellular phenomena as well as pathological conditions influenced by this
      irreversible post-translational protein modification.

PMID- 21902810
TI  - Extracellular TG2: emerging functions and regulation.
AB  - Tissue transglutaminase (TG2) is a ubiquitously expressed member of the
      transglutaminase family of Ca(2+)-dependent crosslinking enzymes. Unlike other
      family members, TG2 is a multifunctional protein, which has several other well
      documented enzymatic and non-enzymatic functions. A significant body of evidence
      accumulated over the last decade reveals multiple and complex activities of this
      protein on the cell surface and in the extracellular matrix (ECM), including its
      role in the regulation of cell-ECM interactions and outside-in signaling by
      several types of transmembrane receptors. Moreover, recent findings indicate a
      dynamic regulation of the levels and functions of extracellular TG2 by several
      complementary mechanisms. This review summarizes and assesses recent research
      into the emerging functions and regulation of extracellular TG2.

PMID- 21902811
TI  - Expression and inducibility of UDP-glucuronosyltransferase 1As in MCF-7 human
      breast carcinoma cells.
AB  - UDP-glucuronosyltransferases (UGTs) are conjugation enzymes, which are regulated
      in a tissue-specific manner by endogenous and environmental factors. In this
      study, we focused on UGT1A isoforms broadly expressed in hepatic and extrahepatic
      tissues and examined the expression and inducibility of UGT1As (UGT1A1 and UGT1A3
      1A10) in MCF-7 cells (human breast carcinoma cell line). Reverse transcription
      polymerase chain reaction (RT-PCR) analysis demonstrated that UGT1A1, UGT1A6 and
      UGT1A9 mRNAs as well as the mRNAs of transcriptional regulators (AhR, aryl
      hydrocarbon receptor; Arnt, AhR nuclear translocator; ERalpha, oestrogen receptor
      alpha; ERbeta, oestrogen receptor beta; and GR, glucocorticoid receptor) are
      expressed in MCF-7 cells. UGT1A6 mRNA level in MCF-7 cells was significantly
      increased to 1.9 times by beta-naphthoflavone (BNF), whereas UGT1A1 and UGT1A9
      mRNA levels were not affected by BNF. There were no significant changes in the
      mRNAs of UGT1A1, UGT1A6 and UGT1A9 in MCF-7 cells by treatment with phenobarbital
      (PB) and dexamethasone (DEX) in MCF-7 cells. The kinetics of 7-ethyl-10
      hydroxycamptothecin (SN-38), 5-hydroxytryptamine (5-HT) and 4-methylumbelliferone
      (4-MU) glucuronidation by microsomes from control and BNF-treated MCF-7 cells
      fitted with the Michaelis-Menten model, and the V(max)  and CL(int)  values were
      significantly increased to 7.5-8.5 times and 5.9-10.4 times by BNF treatment,
      respectively. These findings suggest that BNF induces UGT1A6 in MCF-7 cells and
      that the increase may be mediated by AhR but not pregnane X receptor
      (PXR)/constitutive androstane receptor (CAR). The information gained in this
      study should help predict and assess the toxicity of environmental chemicals.

PMID- 21902812
TI  - Attenuation of liver pro-inflammatory responses by Zingiber officinale via
      inhibition of NF-kappa B activation in high-fat diet-fed rats.
AB  - The aim of this study was to investigate whether treatment with a ginger
      (Zingiber officinale) extract of high-fat diet (HFD)-fed rats suppresses Nuclear
      factor-kappa B (NF-kappaB)-driven hepatic inflammation and to subsequently
      explore the molecular mechanisms in vitro. Adult male Sprague-Dawley rats were
      treated with an ethanolic extract of Zingiber officinale (400 mg/kg) along with a
      HFD for 6 weeks. Hepatic cytokine mRNA levels, cytokine protein levels and NF
      kappaB activation were measured by real-time PCR, Western blot and an NF-kappaB
      nuclear translocation assay, respectively. In vitro, cell culture studies were
      carried out in human hepatocyte (HuH-7) cells by treatment with Zingiber
      officinale (100 MUg/mL) for 24 hr prior to interleukin-1beta (IL-1beta, 8 ng/mL)
      induced inflammation. We showed that Zingiber officinale treatment decreased
      cytokine gene TNFalpha and IL-6 expression in HFD-fed rats, which was associated
      with suppression of NF-kappaB activation. In vitro, Zingiber officinale treatment
      decreased NF-kappaB-target inflammatory gene expression of IL-6, IL-8 and serum
      amyloid A1 (SAA1), while it suppressed NF-kappaB activity, IkappaBalpha
      degradation and IkappaB kinase (IKK) activity. In conclusion, Zingiber officinale
      suppressed markers of hepatic inflammation in HFD-fed rats, as demonstrated by
      decreased hepatic cytokine gene expression and decreased NF-kappaB activation.
      The study demonstrates that the anti-inflammatory effect of Zingiber officinale
      occurs at least in part through the NF-kappaB signalling pathway.

PMID- 21902813
TI  - Gender, but not CYP7A1 or SLCO1B1 polymorphism, affects the fasting plasma
      concentrations of bile acids in human beings.
AB  - Cholesterol 7alpha-hydroxylase (CYP7A1) is the rate-limiting enzyme of bile acid
      production in human beings, and organic anion-transporting polypeptide 1B1
      (OATP1B1) may influence bile acid hepatic uptake and cholesterol and bile acid
      synthesis rate. Our purpose was to investigate the effects of gender and CYP7A1
      and SLCO1B1 polymorphisms on the fasting plasma concentrations of bile acids,
      bile acid synthesis marker and total cholesterol in a Finnish population. Fasting
      plasma concentrations of 16 endogenous bile acids, their synthesis marker (7alpha
      hydroxy-4-cholesten-3-one) and total cholesterol were measured in 243 samples
      from 143 healthy volunteers. The volunteers were genotyped for 6 haplotype
      tagging single-nucleotide polymorphisms (SNPs) of CYP7A1 and two functionally
      relevant SNPs in SLCO1B1. The mean plasma concentrations of chenodeoxycholic
      acid, glycochenodeoxycholic acid, ursodeoxycholic acid and glycoursodeoxycholic
      acid were 61-111% higher in men than in women (P <= 0.001). Accordingly, the mean
      concentration of total bile acids was 51% higher in men than in women (P =
      0.001). The CYP7A1 rs8192879 and rs1023652 SNPs were associated with deoxycholic
      acid and hyodeoxycholic acid concentrations, respectively, but the associations
      were not significant after correction for multiple testing. None of the six
      CYP7A1 SNPs was associated with the plasma concentrations of cholesterol or
      7alpha-hydroxy-4-cholesten-3-one. SLCO1B1 genotype was associated with total
      plasma cholesterol concentration only, but the association was not significant
      after correction for multiple testing. In general, the gender contributes
      substantially more to variation in fasting plasma bile acid concentrations than
      CYP7A1 or SLCO1B1 polymorphism do. Common genetic variability in CYP7A1 is
      unlikely to play a significant role in cholesterol metabolism and bile acid
      homeostasis under normal physiological conditions.

PMID- 21902814
TI  - Physiological remodelling of the maternal uterine circulation during pregnancy.
AB  - Sufficient uteroplacental blood flow is essential for normal pregnancy outcome
      and is accomplished by the coordinated growth and remodelling of the entire
      maternal uterine vasculature. The main focus of this MiniReview is to provide
      information on upstream (pre-placental) maternal uterine vascular remodelling
      that facilitates gestational increases in uterine blood flow. Consideration of
      the three-dimensional pattern of remodelling (circumferential enlargement versus
      axial elongation), changes in vessel biomechanical properties, and underlying
      mechanisms [shear stress, nitric oxide, vascular endothelial growth factor
      (VEGF)/placental growth factor (PlGF), the renin-angiotensin system] and pathways
      (local versus systemic; venoarterial exchange) are provided using the rat as the
      principal animal model, although findings from other species are incorporated
      wherever possible to provide a comparative perspective. The process of maternal
      gestational uterine vascular remodelling involves a number of cellular processes
      and mechanisms, including trophoblast invasion, hyperplasia and hypertrophy, and
      changes in extracellular matrix composition. In addition, changes in cellular
      function, e.g. the secretory and contractile properties of smooth muscle and an
      up-regulation of endothelial vasodilatory influences may contribute to
      uteroplacental blood flow increases through changes in tone as well as in
      structure. Future studies aimed at better understanding the inter-relationship
      between changes in vessel structure (remodelling) and function (reactivity) would
      likely generate new mechanistic insights into the fascinating process of maternal
      gestational uterine vascular adaptation and provide a more physiological
      perspective of the underlying cellular processes involved in its regulation.

PMID- 21902815
TI  - Smooth muscle biomechanics and plasticity: relevance for vascular calibre and
      remodelling.
AB  - Blood vessel structure and calibre are not static. Rather, vessels remodel
      continuously in response to their biomechanical environment. Vascular calibre is
      dictated by the amount, composition and organization of the elastic extracellular
      matrix. In addition, the amount and organization of contractile smooth muscle
      cell (SMC) also need to be regulated. The SMCs are organized such that maximum
      contractile force generally occurs at diameters slightly below the diameter at
      full dilation and physiological pressure. Thus, in a remodelling vessel, not only
      the matrix but also the SMCs need to undergo structural adaptation. Surprisingly
      little is known on the adaptation of SMC contractile properties in the
      vasculature. The purpose of this review is to explore this SMC plasticity in the
      context of vascular remodelling. While not much work on this has been carried out
      on blood vessels, SMC plasticity is more extensively studied on other hollow
      structures such as airway and bladder. We therefore include studies on bladder
      and airway SMCs because of their possible relevance for vascular SMC behaviour.
      Here, plasticity is thought to form an adaptation allowing maintained function
      despite large volume changes. In blood vessels, the general match of active and
      passive diameter-tension relations suggests that SMC plasticity is part of normal
      vascular physiological adaptation. Vascular SMCs display similar processes and
      forms of adaptation as seen in nonvascular SMCs. This may become particularly
      relevant under strong vasoconstriction, when inward cytoskeletal adaptation
      possibly prevents immediate full dilation. This may contribute to structural
      inward remodelling as seen in hypertension and flow reduction.

PMID- 21902816
TI  - Low frequency of Toll-like receptors 2 and 4 gene polymorphisms in Mexican
      patients and their association with type 2 diabetes.
AB  - Type 2 diabetes (T2D) is characterized by a chronic low-grade inflammatory state.
      SNP in Toll-like receptor (TLR) genes has been associated with impaired
      inflammatory response. We genotyped the TLR4/D299G, TLR4/T399I and TLR2/R753Q
      polymorphisms. Low frequency was found with no association with T2D, nevertheless
      the TLR2 SNP was associated with lower levels in HDL-cholesterol values.

PMID- 21902817
TI  - Determination of H5N1 vaccine potency using reference antisera from heterologous
      strains of influenza.
AB  - BACKGROUND: Standardization of inactivated influenza vaccines by hemagglutinin
      (HA) content is performed by the single radial immunodiffusion (SRID) method.
      Regulatory agencies prepare, calibrate, and distribute SRID reagent standards
      necessary for testing of seasonal influenza vaccines, and a similar process is
      used to produce potency reagents for candidate pandemic influenza vaccines that
      are manufactured for emergency stockpiles. OBJECTIVES: Because of the concerns in
      generating a timely strain-specific potency antiserum for an emerging pandemic
      virus, we evaluated the feasibility of using heterologous potency reference
      antiserum as a replacement for a strain-specific (homologous) antiserum in the
      SRID potency assay for stockpiled H5N1 vaccines. RESULTS: The results indicate
      that a heterologous H5N1 antiserum can be used to determine the accurate potency
      of inactivated H5N1 influenza vaccines. Additionally, when H5N1 vaccine was
      subjected to an accelerated stability protocol, both homologous and heterologous
      antisera provided similar measurements of vaccine potency decline. Limitations to
      the heterologous antiserum approach to potency determination were shown by the
      inability of antiserum to recent seasonal H1N1 viruses to work in an SRID assay
      with the 2009 pandemic H1N1 A/California/07/2009 antigen. CONCLUSIONS: The data
      demonstrate the feasibility of using heterologous antiserum for potency
      determination of at least some candidate vaccines in case of a shortage or delay
      of homologous antiserum. Further, the results suggest the prudence of stockpiling
      a broad library of potency reagents including many strains of influenza viruses
      with pandemic potential to provide an added measure of assurance that reagent
      production would not be a bottleneck to vaccine production during a pandemic.

PMID- 21902818
TI  - The increased prevalence of myopia in Finland.
AB  - PURPOSE: To study change in the prevalence of myopia in Finland during the 20th
      century. METHODS: A review of the literature on the prevalence of myopia in
      Finland. RESULTS: During the 20th century, the prevalence of myopia among 7- to 8
      year-old schoolchildren did not increase in Finland and varied between 0.5% and
      1.9%. Among 14- to 15-year-old school children, myopia doubled to about 21%.
      Among adults born during the first three decades of the 20th century, the
      prevalence of myopia was <10%, whereas among those born during the second half of
      the 20th century, the prevalence rose to 21-30%. The change in mean refraction
      was towards myopia. CONCLUSIONS: During the course of the 20th century, myopia
      among teenagers and adults in Finland significantly increased and the mean change
      in refraction was towards myopia. Increased education is proposed as the main
      reason behind these changes.

PMID- 21902819
TI  - Atypical hemolytic uremic syndrome.
AB  - Hemolytic uremic syndrome (HUS) is defined by the triad of mechanical hemolytic
      anemia, thrombocytopenia and renal impairment. Atypical HUS (aHUS) defines non
      Shiga-toxin-HUS and even if some authors include secondary aHUS due to
      Streptococcus pneumoniae or other causes, aHUS designates a primary disease due
      to a disorder in complement alternative pathway regulation. Atypical HUS
      represents 5 -10% of HUS in children, but the majority of HUS in adults. The
      incidence of complement-aHUS is not known precisely. However, more than 1000 aHUS
      patients investigated for complement abnormalities have been reported. Onset is
      from the neonatal period to the adult age. Most patients present with hemolytic
      anemia, thrombocytopenia and renal failure and 20% have extra renal
      manifestations. Two to 10% die and one third progress to end-stage renal failure
      at first episode. Half of patients have relapses. Mutations in the genes encoding
      complement regulatory proteins factor H, membrane cofactor protein (MCP), factor
      I or thrombomodulin have been demonstrated in 20-30%, 5-15%, 4-10% and 3-5% of
      patients respectively, and mutations in the genes of C3 convertase proteins, C3
      and factor B, in 2-10% and 1-4%. In addition, 6-10% of patients have anti-factor
      H antibodies. Diagnosis of aHUS relies on 1) No associated disease 2) No criteria
      for Shigatoxin-HUS (stool culture and PCR for Shiga-toxins; serology for anti
      lipopolysaccharides antibodies) 3) No criteria for thrombotic thrombocytopenic
      purpura (serum ADAMTS 13 activity > 10%). Investigation of the complement system
      is required (C3, C4, factor H and factor I plasma concentration, MCP expression
      on leukocytes and anti-factor H antibodies; genetic screening to identify risk
      factors). The disease is familial in approximately 20% of pedigrees, with an
      autosomal recessive or dominant mode of transmission. As penetrance of the
      disease is 50%, genetic counseling is difficult. Plasmatherapy has been first
      line treatment until presently, without unquestionable demonstration of
      efficiency. There is a high risk of post-transplant recurrence, except in MCP
      HUS. Case reports and two phase II trials show an impressive efficacy of the
      complement C5 blocker eculizumab, suggesting it will be the next standard of
      care. Except for patients treated by intensive plasmatherapy or eculizumab, the
      worst prognosis is in factor H-HUS, as mortality can reach 20% and 50% of
      survivors do not recover renal function. Half of factor I-HUS progress to end
      stage renal failure. Conversely, most patients with MCP-HUS have preserved renal
      function. Anti-factor H antibodies-HUS has favourable outcome if treated early.

PMID- 21902820
TI  - Developing risk prediction models for type 2 diabetes: a systematic review of
      methodology and reporting.
AB  - BACKGROUND: The World Health Organisation estimates that by 2030 there will be
      approximately 350 million people with type 2 diabetes. Associated with renal
      complications, heart disease, stroke and peripheral vascular disease, early
      identification of patients with undiagnosed type 2 diabetes or those at an
      increased risk of developing type 2 diabetes is an important challenge. We sought
      to systematically review and critically assess the conduct and reporting of
      methods used to develop risk prediction models for predicting the risk of having
      undiagnosed (prevalent) or future risk of developing (incident) type 2 diabetes
      in adults. METHODS: We conducted a systematic search of PubMed and EMBASE
      databases to identify studies published before May 2011 that describe the
      development of models combining two or more variables to predict the risk of
      prevalent or incident type 2 diabetes. We extracted key information that
      describes aspects of developing a prediction model including study design, sample
      size and number of events, outcome definition, risk predictor selection and
      coding, missing data, model-building strategies and aspects of performance.
      RESULTS: Thirty-nine studies comprising 43 risk prediction models were included.
      Seventeen studies (44%) reported the development of models to predict incident
      type 2 diabetes, whilst 15 studies (38%) described the derivation of models to
      predict prevalent type 2 diabetes. In nine studies (23%), the number of events
      per variable was less than ten, whilst in fourteen studies there was insufficient
      information reported for this measure to be calculated. The number of candidate
      risk predictors ranged from four to sixty-four, and in seven studies it was
      unclear how many risk predictors were considered. A method, not recommended to
      select risk predictors for inclusion in the multivariate model, using statistical
      significance from univariate screening was carried out in eight studies (21%),
      whilst the selection procedure was unclear in ten studies (26%). Twenty-one risk
      prediction models (49%) were developed by categorising all continuous risk
      predictors. The treatment and handling of missing data were not reported in 16
      studies (41%). CONCLUSIONS: We found widespread use of poor methods that could
      jeopardise model development, including univariate pre-screening of variables,
      categorisation of continuous risk predictors and poor handling of missing data.
      The use of poor methods affects the reliability of the prediction model and
      ultimately compromises the accuracy of the probability estimates of having
      undiagnosed type 2 diabetes or the predicted risk of developing type 2 diabetes.
      In addition, many studies were characterised by a generally poor level of
      reporting, with many key details to objectively judge the usefulness of the
      models often omitted.

PMID- 21902821
TI  - Distribution of sialic acid receptors and influenza A virus of avian and swine
      origin in experimentally infected pigs.
AB  - BACKGROUND: Pigs are considered susceptible to influenza A virus infections from
      different host origins because earlier studies have shown that they have
      receptors for both avian (sialic acid-alpha-2,3-terminal saccharides (SA-alpha
      2,3)) and swine/human (SA-alpha-2,6) influenza viruses in the upper respiratory
      tract. Furthermore, experimental and natural infections in pigs have been
      reported with influenza A virus from avian and human sources. METHODS: This study
      investigated the receptor distribution in the entire respiratory tract of pigs
      using specific lectins Maackia Amurensis (MAA) I, and II, and Sambucus Nigra
      (SNA). Furthermore, the predilection sites of swine influenza virus (SIV)
      subtypes H1N1 and H1N2 as well as avian influenza virus (AIV) subtype H4N6 were
      investigated in the respiratory tract of experimentally infected pigs using
      immunohistochemical methods. RESULTS: SIV antigen was widely distributed in
      bronchi, but was also present in epithelial cells of the nose, trachea,
      bronchioles, and alveolar type I and II epithelial cells in severely affected
      animals. AIV was found in the lower respiratory tract, especially in alveolar
      type II epithelial cells and occasionally in bronchiolar epithelial cells. SA
      alpha-2,6 was the predominant receptor in all areas of the respiratory tract with
      an average of 80-100% lining at the epithelial cells. On the contrary, the SA
      alpha-2,3 was not present (0%) at epithelial cells of nose, trachea, and most
      bronchi, but was found in small amounts in bronchioles, and in alveoli reaching
      an average of 20-40% at the epithelial cells. Interestingly, the receptor
      expression of both SA-alpha-2,3 and 2,6 was markedly diminished in influenza
      infected areas compared to non-infected areas. CONCLUSIONS: A difference in
      predilection sites between SIV and AIV virus was found, and this difference was
      in accordance with the distribution of the SA-alpha-2,6 and SA-alpha-2,3
      receptor, respectively. The results indicated that the distribution of influenza
      A virus receptors in pigs are similar to that of humans and therefore challenge
      the theory that the pig acts as a mixing vessel between human and avian influenza
      viruses. Furthermore, it was shown that AIV prefers to infect alveolar type II
      epithelial cells in pigs. This corresponds with findings in humans emphasising
      the resemblance between the two species.

PMID- 21902822
TI  - Hepatitis C virus genotypes in Pakistan: a systemic review.
AB  - BACKGROUND AND AIM: Phylogenetic analysis has led to the classification of
      hepatitis C virus (HCV) into 1-6 major genotypes. HCV genotypes have different
      biological properties, clinical outcome and response to antiviral treatment and
      provide important clues for studying the epidemiology, transmission and
      pathogenesis. This article deepens the current molecular information about the
      geographical distribution of HCV genotypes and subgenotypes in population of four
      provinces of Pakistan. 34 published papers (1996-2011) related to prevalence of
      HCV genotypes/serotypes and subgenotypes in Pakistan were searched. RESULT: HCV
      genotype/s distribution from all 34 studies was observed in 28,400 HCV infected
      individuals in the following pattern: 1,999 (7.03%) cases of genotype 1; 1,085
      (3.81%) cases of genotype 2; 22,429 (78.96%) cases of genotype 3; 453 (1.59%)
      cases of genotype 4; 29 (0.10%) cases of genotype 5; 37 (0.13%) cases of genotype
      6; 1,429 (5.03%) cases of mixed genotypes, and 939 (3.30%) cases of untypeable
      genotypes. Overall, genotype 3a was the predominant genotype with a rate of
      55.10%, followed by genotype 1a, 3b and mixed genotype with a rate of 10.25%,
      8.20%, and 5.08%, respectively; and genotypes 4, 5 and 6 were rare. Genotype 3
      occurred predominately in all the provinces of Pakistan. Second more frequently
      genotype was genotype 1 in Punjab province and untypeable genotypes in Sindh,
      Khyber Pakhtunkhwa and Balochistan provinces.

PMID- 21902823
TI  - Managing patients with dengue fever during an epidemic: the importance of a
      hydration tent and of a multidisciplinary approach.
AB  - BACKGROUND: Dengue fever is one of the most common tropical diseases worldwide.
      Early detection of the disease, followed by intravenous fluid therapy in patients
      with dengue hemorrhagic fever (DHF) or with warning signs of dengue has a major
      impact on the prognosis. The purpose of this study is to describe the care
      provided in a hydration tent, including early detection, treatment, and serial
      follow-up of patients with dengue fever. FINDINGS: The analysis included all
      patients treated in the hydration tent from April 8 to May 9, 2008. The tent was
      set up inside the premises of the 2nd Military Firemen Group, located in Meier, a
      neighborhood in Rio de Janeiro, Brazil. The case form data were stored in a
      computerized database for subsequent assessment. Patients were referred to the
      tent from primary care units and from secondary city and state hospitals. The
      routine procedure consisted of an initial screening including vital signs
      (temperature, blood pressure, heart rate, and respiratory rate), tourniquet test
      and blood sampling for complete blood count. Over a 31-day period, 3,393 case
      recordings were seen at the hydration tent. The mean was 109 patients per day. A
      total of 2,102 initial visits and 1,291 return visits were conducted. Of the
      patients who returned to the hydration tent for reevaluation, 850 returned once,
      230 returned twice, 114 returned three times, and 97 returned four times or more.
      Overall, 93 (5.3%) patients with DHF seen at the tent were transferred to a
      tertiary hospital. There were no deaths among these patients. DISCUSSION: As the
      epidemics were already widespread and there were no technical conditions for
      routine serology, all cases of suspected dengue fever were treated as such.
      Implementing hydration tents decrease the number of dengue fever
      hospitalizations.

PMID- 21902824
TI  - Implications of controlled short-wavelength light exposure for sleep in older
      adults.
AB  - BACKGROUND: Environmental and physiological conditions make older adults more
      likely to lose synchronization to their local time and experience sleep
      disturbances. A regular, 24-hour light/dark cycle promotes synchronization. It is
      now well established that the circadian system is maximally sensitive to short
      wavelength (blue) light. The purpose of the present study was to measure dose
      effectiveness (amounts and durations) of short-wavelength (blue) light for
      stimulating the circadian systems of older adults. We investigated the impact of
      six corneal irradiances (0.7 to 72 MUW/cm2) of 470-nm light on nocturnal
      melatonin production. Nine participants, each over 50 years of age completed a
      within-subjects study. Each week, participants were exposed to one of the six
      irradiances of 470-nm light for 90 minutes. FINDINGS: A two-factor (6 corneal
      irradiances * 10 exposure durations), within-subjects analysis of variance
      (ANOVA) was conducted using the melatonin suppression levels. The ANOVA revealed
      a significant main effect of corneal irradiance (F5, 30 = 9.131, p < 0.0001), a
      significant main effect of exposure duration (F9, 54 = 5.731, p < 0.0001), and a
      significant interaction between these two variables (F45,270 = 1.927, p < 0.001).
      Post hoc t-tests revealed that corneal irradiances as low as 2 MUW/cm2 reliably
      suppressed melatonin after 90-minute exposure whereas 0.7 MUW/cm2 did not.
      CONCLUSIONS: Sleep disorders are common and a serious problem for millions of
      older adults. The present results showed that comfortable, precise and effective
      doses of light can be prescribed to older adults to reliably stimulate the
      circadian system that presumably would promote entrainment and, thus, regular
      sleep. Field studies on the impact of short-wavelength-light doses on sleep
      efficiency in older adults should be performed.

PMID- 21902825
TI  - SNIT: SNP identification for strain typing.
AB  - With ever-increasing numbers of microbial genomes being sequenced, efficient
      tools are needed to perform strain-level identification of any newly sequenced
      genome. Here, we present the SNP identification for strain typing (SNIT)
      pipeline, a fast and accurate software system that compares a newly sequenced
      bacterial genome with other genomes of the same species to identify single
      nucleotide polymorphisms (SNPs) and small insertions/deletions (indels). Based on
      this information, the pipeline analyzes the polymorphic loci present in all input
      genomes to identify the genome that has the fewest differences with the newly
      sequenced genome. Similarly, for each of the other genomes, SNIT identifies the
      input genome with the fewest differences. Results from five bacterial species
      show that the SNIT pipeline identifies the correct closest neighbor with 75% to
      100% accuracy. The SNIT pipeline is available for download at
      http://www.bhsai.org/snit.html.

PMID- 21902826
TI  - Isolated adult hypoganglionosis presenting as sigmoid volvulus: a case report.
AB  - INTRODUCTION: Isolated hypoganglionosis is a rare cause of intestinal innervation
      defects. It is characterized by sparse and small myenteric ganglia, absent or low
      acetylcholinesterase activity in the lamina propria and hypertrophy of the
      muscularis mucosae, principally in the region of the colon and rectum. It
      accounts for 5% of all intestinal neuronal malformations. To the best of our
      knowledge, only 92 cases of isolated hypoganglionosis were reported from 1978 to
      2009. Isolated hypoganglionosis usually manifests as enterocolitis or poor bowel
      function, and is diagnosed in infancy or childhood. We report the first case of
      isolated hypoganglionosis presenting with sigmoid volvulus in a 34-year-old
      woman. CASE PRESENTATION: A 34-year-old Asian woman had progressively increasing
      abdominal pain and had not passed stool or flatus for two days. A physical
      examination revealed a distended abdomen with sluggish gut sounds. A computerized
      tomography (CT) scan demonstrated gross dilatation of the sigmoid colon (maximal
      diameter 14.3 cm) suggestive of sigmoid volvulus. During emergency laparotomy,
      sigmoidectomy with a side-to-side colorectal anastomosis was performed.
      Histopathology of the resected specimen showed occasional ganglion cells and
      hypertrophied nerve bundles in the muscle layers, suggesting hypoganglionosis.
      Colonoscopy was performed, and multiple full-thickness biopsies were taken that
      showed hypoganglionosis of the entire large bowel. Our patient underwent total
      colectomy with an ileorectal anastomosis. Subsequently our patient reported a
      dramatic improvement in her bowel function. CONCLUSIONS: Isolated
      hypoganglionosis is a rare cause of intestinal dysganglionosis and cannot be
      differentiated from Hirschsprung's disease based on clinical presentation. This
      case report describes an atypical presentation of the disease. A definitive
      diagnosis requires histopathological analysis of full-thickness intestinal
      biopsies. Treatment should be tailored to the extent of hypoganglionosis.

PMID- 21902827
TI  - Challenges in clinical and laboratory diagnosis of androgen insensitivity
      syndrome: a case report.
AB  - INTRODUCTION: Androgen is a generic term usually applied to describe a group of
      sex steroid hormones. Androgens are responsible for male sex differentiation
      during embryogenesis at the sixth or seventh week of gestation, triggering the
      development of the testes and penis in male fetuses, and are directed by the
      testicular determining factor: the gene SRY (sex determining region on Y
      chromosome) located on the short arm of chromosome Y. The differentiation of male
      external genitalia (penis, scrotum and penile urethra) occurs between the 9th and
      13th weeks of pregnancy and requires adequate concentration of testosterone and
      the conversion of this to another more potent androgen, dihydrotestosterone,
      through the action of 5alpha-reductase in target tissues. CASE PRESENTATION: This
      report describes the case of a teenage girl presenting with a male karyotype, and
      aims to determine the extension of the mutation that affected the AR gene. A
      Caucasian girl aged 15 was referred to our laboratory for genetic testing due to
      primary amenorrhea. Physical examination, karyotype testing and molecular
      analysis of the androgen receptor were critical in making the correct diagnosis
      of complete androgen insensitivity syndrome. CONCLUSIONS: Sex determination and
      differentiation depend on a cascade of events that begins with the establishment
      of chromosomal sex at fertilization and ends with sexual maturation at puberty,
      subsequently leading to fertility. Mutations affecting the AR gene may cause
      either complete or partial androgen insensitivity syndrome. The case reported
      here is consistent with complete androgen insensitivity syndrome, misdiagnosed at
      birth, and consequently our patient was raised both socially and educationally as
      a female. It is critical that health care providers understand the importance of
      properly diagnosing a newborn manifesting ambiguous genitalia. Furthermore, a
      child with a pseudohermaphrodite phenotype should always undergo adequate
      endocrine and genetic testing to reach a conclusive diagnosis before gender is
      assigned and surgical interventions are carried out. Our results show that
      extreme care must be taken in selecting the genetic tools that are utilized for
      the diagnosis for androgen insensitivity syndrome.

PMID- 21902828
TI  - Dysphagia as a manifestation of esophageal tuberculosis: a report of two cases.
AB  - INTRODUCTION: Esophageal involvement by Mycobacterium tuberculosis is rare and
      the diagnosis is frequently made by means of an esophageal biopsy during the
      evaluation of dysphagia. There are few cases reported in the literature. CASE
      PRESENTATION: We present two cases of esophageal tuberculosis in 85- and 65-year
      old male Caucasian patients with initial complaints of dysphagia and epigastric
      pain. Upper gastrointestinal endoscopy resulted in the diagnosis of esophageal
      tuberculosis following the biopsy of lesions of irregular mucosa in one case and
      a sessile polyp in the other. Pulmonary tuberculosis was detected in one patient.
      In one patient esophageal stricture developed as a complication. Antituberculous
      therapy was curative in both patients. CONCLUSION: Although rare, esophageal
      tuberculosis has to be kept in mind in the differential diagnosis of dysphagia.
      Pulmonary involvement has important implications for contact screening.

PMID- 21902829
TI  - Engineering strategy of yeast metabolism for higher alcohol production.
AB  - BACKGROUND: While Saccharomyces cerevisiae is a promising host for cost-effective
      biorefinary processes due to its tolerance to various stresses during
      fermentation, the metabolically engineered S. cerevisiae strains exhibited rather
      limited production of higher alcohols than that of Escherichia coli. Since the
      structure of the central metabolism of S. cerevisiae is distinct from that of E.
      coli, there might be a problem in the structure of the central metabolism of S.
      cerevisiae. In this study, the potential production of higher alcohols by S.
      cerevisiae is compared to that of E. coli by employing metabolic simulation
      techniques. Based on the simulation results, novel metabolic engineering
      strategies for improving higher alcohol production by S. cerevisiae were
      investigated by in silico modifications of the metabolic models of S. cerevisiae.
      RESULTS: The metabolic simulations confirmed that the high production of butanols
      and propanols by the metabolically engineered E. coli strains is derived from the
      flexible behavior of their central metabolism. Reducing this flexibility by gene
      deletion is an effective strategy to restrict the metabolic states for producing
      target alcohols. In contrast, the lower yield using S. cerevisiae originates from
      the structurally limited flexibility of its central metabolism in which gene
      deletions severely reduced cell growth. CONCLUSIONS: The metabolic simulation
      demonstrated that the poor productivity of S. cerevisiae was improved by the
      introduction of E. coli genes to compensate the structural difference. This
      suggested that gene supplementation is a promising strategy for the metabolic
      engineering of S. cerevisiae to produce higher alcohols which should be the next
      challenge for the synthetic bioengineering of S. cerevisiae for the efficient
      production of higher alcohols.

PMID- 21902830
TI  - A male case of an undifferentiated carcinoma with osteoclast-like giant cells
      originating in an indeterminate mucin-producing cystic neoplasm of the pancreas.
      A case report and review of the literature.
AB  - We report a rare male case of an undifferentiated carcinoma with osteoclast-like
      giant cells originating in an indeterminate mucin-producing cystic neoplasm of
      the pancreas. A 59-year-old Japanese man with diabetes visited our hospital,
      complaining of fullness in the upper abdomen. A laboratory analysis revealed
      anemia (Hemoglobin; 9.7 g/dl) and elevated C-reactive protein (3.01 mg/dl).
      Carbohydrate antigen 19-9 was 274 U/ml and Carcinoembryonic antigen was 29.6
      ng/ml. A computed tomography scan of the abdomen revealed a 14-cm cystic mass in
      the upper left quadrant of the abdomen that appeared to originate from the
      pancreatic tail. The patient underwent distal pancreatectomy/splenectomy/total
      gastrectomy/cholecystectomy. The mass consisted of a multilocular cystic lesion.
      Microscopically, the cyst was lined by cuboidal or columnar epithelium, including
      mucinous epithelium. Sarcomatous mononuclear cells and multinucleated osteoclast
      like giant cells were found in the stroma. Ovarian-type stroma was not seen. We
      made a diagnosis of osteoclast-like giant cell tumor originating in an
      indeterminate mucin-producing cystic neoplasm of the pancreas. All surgical
      margins were negative, however, two peripancreatic lymph nodes were positive. The
      patient recovered uneventfully. Two months after the operation, multiple
      metastases occurred in the liver. He died 4 months after the operation.

PMID- 21902832
TI  - Why do GPs hesitate to refer diabetes patients to a self-management education
      program: a qualitative study.
AB  - BACKGROUND: Self-management support is seen as a cornerstone of good diabetes
      care and many countries are currently engaged in initiatives to integrate self
      management support in primary care. Concerning the organisation of these
      programs, evidence is growing that engagement of health care professionals, in
      particular of GPs, is critical for successful application. This paper reports on
      a study exploring why a substantial number of GPs was (initially) reluctant to
      refer patients to a self-management education program in Belgium. METHODS:
      Qualitative analysis of semi-structured face-to-face interviews with a purposive
      sample of 20 GPs who were not regular users of the service. The Greenhalgh
      diffusion of innovation framework was used as background and organising
      framework. RESULTS: Several barriers, linked to different components of the
      Greenhalgh model, emerged from the interview data. One of the most striking ones
      was the limited readiness for innovation among GPs. Feelings of fear of further
      fragmentation of diabetes care and frustration and insecurity regarding their own
      role in diabetes care prevented them from engaging in the innovation process. GPs
      needed time to be reassured that the program respects their role and has an added
      value to usual care. Once GPs considered referring patients, it was not clear
      enough which of their patients would benefit from the program. Some GPs expressed
      the need for training in motivational skills, so that they could better motivate
      their patients to participate. A practical but often mentioned barrier was the
      distance to the centre where the program was delivered. Further, uncertainty
      about continuity interfered with the uptake of the offer. CONCLUSIONS: The study
      results contribute to a better understanding of the reasons why GPs hesitate to
      refer patients to a self-management education program. First of all, the role of
      GPs and other health care providers in diabetes care needs to be clarified before
      introducing new functions. Feelings of security and a basic trust of providers in
      the health system are a prerequisite for participation in care innovation.
      Moreover, some important lessons regarding the implementation of an education
      program in primary care have been learned from the study.

PMID- 21902833
TI  - Investigation of an Escherichia coli O145 outbreak in a child day-care centre-
      extensive sampling and characterization of eae- and stx1-positive E. coli yields
      epidemiological and socioeconomic insight.
AB  - BACKGROUND: On October 29th 2009 the health authorities in the city of Trondheim,
      Norway were alerted about a case of Shiga toxin-positive E. coli (STEC) O145 in a
      child with bloody diarrhoea attending a day-care centre. Symptomatic children in
      this day-care centre were sampled, thereby identifying three more cases. This
      initiated an outbreak investigation. METHODS: A case was defined as a child
      attending the day-care centre, in whom eae- and stx1- but not stx2-positive E.
      coli O145:H28 was diagnosed from a faecal sample, with multilocus variable number
      of tandem repeat analysis (MLVA) profile identical to the index isolate. All 61
      children, a staff of 14 in the day-care centre, and 74 close contacts submitted
      faecal samples. Staff and parents were interviewed about cases' exposure to foods
      and animals. Faecal samples from 31 ewes from a sheep herd to which the children
      were exposed were analyzed for E. coli O145. RESULTS: Sixteen cases were
      identified, from which nine presented diarrhoea but not haemolytic uremic
      syndrome (HUS). The attack rate was 0.26, and varied between age groups (0.13
      0.40) and between the three day-care centre departments (0.20-0.50), and was
      significantly higher amongst the youngest children. Median duration of shedding
      was 20 days (0-71 days). Children were excluded from the day-care centre during
      shedding, requiring parents to take compassionate leave, estimated to be a
      minimum total of 406 days for all cases. Atypical enteropathogenic E. coli
      (aEPEC) were detected among 14 children other than cases. These isolates were
      genotypically different from the outbreak strain. Children in the day-care centre
      were exposed to faecal pollution from a sheep herd, but E. coli O145 was not
      detected in the sheep. CONCLUSIONS: We report an outbreak of stx1- and eae
      positive STEC O145:H28 infection with mild symptoms among children in a day-care
      centre. Extensive sampling showed occurrence of the outbreak strain as well as
      other STEC and aEPEC strains in the outbreak population. MLVA-typing of the STEC
      isolates strongly indicates a common source of infection. The study describes
      epidemiological aspects and socioeconomic consequences of a non-O157 STEC
      outbreak, which are less commonly reported than O157 outbreaks.

PMID- 21902831
TI  - The myogenic kinome: protein kinases critical to mammalian skeletal myogenesis.
AB  - Myogenesis is a complex and tightly regulated process, the end result of which
      is the formation of a multinucleated myofibre with contractile capability.
      Typically, this process is described as being regulated by a coordinated
      transcriptional hierarchy. However, like any cellular process, myogenesis is also
      controlled by members of the protein kinase family, which transmit and execute
      signals initiated by promyogenic stimuli. In this review, we describe the various
      kinases involved in mammalian skeletal myogenesis: which step of myogenesis a
      particular kinase regulates, how it is activated (if known) and what its
      downstream effects are. We present a scheme of protein kinase activity, similar
      to that which exists for the myogenic transcription factors, to better clarify
      the complex signalling that underlies muscle development.

PMID- 21902835
TI  - Effect of heme oxygenase-1 polymorphisms on lung function and gene expression.
AB  - BACKGROUND: Oxidative stress induced by smoking is considered to be important in
      the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD). Heme oxygenase
      1 (HMOX1) is an essential enzyme in heme catabolism that is induced by oxidative
      stress and may play a protective role as an antioxidant in the lung. We
      determined whether HMOX1 polymorphisms were associated with lung function in COPD
      patients and whether the variants had functional effects. METHODS: We genotyped
      five single nucleotide polymorphisms (SNPs) in the HMOX1 gene in Caucasians who
      had the fastest (n = 278) and the slowest (n = 304) decline of FEV1 % predicted,
      selected from smokers in the NHLBI Lung Health Study. These SNPs were also
      studied in Caucasians with the lowest (n = 535) or the highest (n = 533) baseline
      lung function. Reporter genes were constructed containing three HMOX1 promoter
      polymorphisms and the effect of these polymorphisms on H2O2 and hemin-stimulated
      gene expression was determined. The effect of the HMOX1 rs2071749 SNP on gene
      expression in alveolar macrophages was investigated. RESULTS: We found a nominal
      association (p = 0.015) between one intronic HMOX1 SNP (rs2071749) and lung
      function decline but this did not survive correction for multiple comparisons.
      This SNP was in perfect linkage disequilibrium with rs3761439, located in the
      promoter of HMOX1. We tested rs3761439 and two other putatively functional
      polymorphisms (rs2071746 and the (GT)n polymorphism) in reporter gene assays but
      no significant effects on gene expression were found. There was also no effect of
      rs2071749 on HMOX1 gene expression in alveolar macrophages. CONCLUSIONS: We found
      no association of the five HMOX1 tag SNPs with lung function decline and no
      evidence that the three promoter polymorphisms affected the regulation of the
      HMOX1 gene.

PMID- 21902834
TI  - Genetic diagnosis of X-linked dominant Hypophosphatemic Rickets in a cohort
      study: tubular reabsorption of phosphate and 1,25(OH)2D serum levels are
      associated with PHEX mutation type.
AB  - BACKGROUND: Genetic Hypophosphatemic Rickets (HR) is a group of diseases
      characterized by renal phosphate wasting with inappropriately low or normal 1,25
      dihydroxyvitamin D3 (1,25(OH)2D) serum levels. The most common form of HR is X
      linked dominant HR (XLHR) which is caused by inactivating mutations in the PHEX
      gene. The purpose of this study was to perform genetic diagnosis in a cohort of
      patients with clinical diagnosis of HR, to perform genotype-phenotype
      correlations of those patients and to compare our data with other HR cohort
      studies. METHODS: Forty three affected individuals from 36 non related families
      were analyzed. For the genetic analysis, the PHEX gene was sequenced in all of
      the patients and in 13 cases the study was complemented by mRNA sequencing and
      Multiple Ligation Probe Assay. For the genotype-phenotype correlation study, the
      clinical and biochemical phenotype of the patients was compared with the type of
      mutation, which was grouped into clearly deleterious or likely causative, using
      the Mann-Whitney and Fisher's exact test. RESULTS: Mutations in the PHEX gene
      were identified in all the patients thus confirming an XLHR. Thirty four
      different mutations were found distributed throughout the gene with higher
      density at the 3' end. The majority of the mutations were novel (69.4%), most of
      them resulted in a truncated PHEX protein (83.3%) and were family specific
      (88.9%). Tubular reabsorption of phosphate (TRP) and 1,25(OH)2D serum levels were
      significantly lower in patients carrying clearly deleterious mutations than in
      patients carrying likely causative ones (61.39 +/- 19.76 vs. 80.14 +/- 8.80%, p =
      0.028 and 40.93 +/- 30.73 vs. 78.46 +/- 36.27 pg/ml, p = 0.013). CONCLUSIONS:
      PHEX gene mutations were found in all the HR cases analyzed, which was in
      contrast with other cohort studies. Patients with clearly deleterious PHEX
      mutations had lower TRP and 1,25(OH)2D levels suggesting that the PHEX type of
      mutation might predict the XLHR phenotype severity.

PMID- 21902836
TI  - Chikungunya triggers an autophagic process which promotes viral replication.
AB  - BACKGROUND: Chikungunya Virus (ChikV) surprised by a massive re-emerging outbreak
      in Indian Ocean in 2006, reaching Europe in 2007 and exhibited exceptional severe
      physiopathology in infants and elderly patients. In this context, it is important
      to analyze the innate immune host responses triggered against ChikV. Autophagy
      has been shown to be an important component of the innate immune response and is
      involved in host defense elimination of different pathogens. However, the
      autophagic process was recently observed to be hijacked by virus for their own
      replication. Here we provide the first evidence that hallmarks of autophagy are
      specifically found in HEK.293 infected cells and are involved in ChikV
      replication. METHODS: To test the capacity of ChikV to mobilize the autophagic
      machinery, we performed fluorescence microscopy experiments on HEK.GFP.LC3 stable
      cells, and followed the LC3 distribution during the time course of ChikV
      infection. To confirm this, we performed electron microscopy on HEK.293 infected
      cells. To test the effect of ChikV-induced-autophagy on viral replication, we
      blocked the autophagic process, either by pharmacological (3-MA) or genetic
      inhibition (siRNA against the transcript of Beclin 1, an autophagic protein), and
      analyzed the percentage of infected cells and the viral RNA load released in the
      supernatant. Moreover, the effect of induction of autophagy by Rapamycin on viral
      replication was tested. RESULTS: The increasing number of GFP-LC3 positive cells
      with a punctate staining together with the enhanced number of GFP-LC3 dots per
      cell showed that ChikV triggered an autophagic process in HEK.293 infected cells.
      Those results were confirmed by electron microscopy analysis since numerous
      membrane-bound vacuoles characteristic of autophagosomes were observed in
      infected cells. Moreover, we found that inhibition of autophagy, either by
      biochemical reagent and RNA interference, dramatically decreases ChikV
      replication. CONCLUSIONS: Taken together, our results suggest that autophagy may
      play a promoting role in ChikV replication. Investigating in details the
      relationship between autophagy and viral replication will greatly improve our
      knowledge of the pathogenesis of ChikV and provide insight for the design of
      candidate antiviral therapeutics.

PMID- 21902839
TI  - Trials of large group teaching in Malaysian private universities: a cross
      sectional study of teaching medicine and other disciplines.
AB  - BACKGROUND: This is a pilot cross sectional study using both quantitative and
      qualitative approach towards tutors teaching large classes in private
      universities in the Klang Valley (comprising Kuala Lumpur, its suburbs, adjoining
      towns in the State of Selangor) and the State of Negeri Sembilan, Malaysia. The
      general aim of this study is to determine the difficulties faced by tutors when
      teaching large group of students and to outline appropriate recommendations in
      overcoming them. FINDINGS: Thirty-two academics from six private universities
      from different faculties such as Medical Sciences, Business, Information
      Technology, and Engineering disciplines participated in this study. SPSS software
      was used to analyse the data. The results in general indicate that the
      conventional instructor-student approach has its shortcoming and requires
      changes. Interestingly, tutors from Medicine and IT less often faced difficulties
      and had positive experience in teaching large group of students. CONCLUSION:
      However several suggestions were proposed to overcome these difficulties ranging
      from breaking into smaller classes, adopting innovative teaching, use of
      interactive learning methods incorporating interactive assessment and creative
      technology which enhanced students learning. Furthermore the study provides
      insights on the trials of large group teaching which are clearly identified to
      help tutors realise its impact on teaching. The suggestions to overcome these
      difficulties and to maximize student learning can serve as a guideline for tutors
      who face these challenges.

PMID- 21902838
TI  - Comparing the accuracy of the three popular clinical dehydration scales in
      children with diarrhea.
AB  - BACKGROUND: Dehydration due to acute gastroenteritis is one of the leading causes
      of mortality in children worldwide. The World Health Organization (WHO) scale,
      the Gorelick scale, and the Clinical Dehydration Scale (CDS) were created to
      estimate percentage dehydration in children with gastroenteritis based on
      clinical signs. Of these, only the CDS has been prospectively validated against a
      valid gold standard, though never in low- and middle-income countries. The
      purpose of this study is to determine whether these clinical scales can
      accurately assess dehydration status in children when performed by nurses or
      general physicians in a low-income country. METHODS: We prospectively enrolled a
      non-consecutive sample of children presenting to three Rwandan hospitals with
      diarrhea and/or vomiting. A health care provider documented clinical signs on
      arrival and weighed the patient using a standard scale. Once admitted, the
      patient received rehydration according to standard hospital protocol and was
      weighed again at hospital discharge. Receiver operating characteristic (ROC)
      curves were created for each of the three scales compared to the gold standard,
      percent weight change with rehydration. Sensitivity, specificity, and likelihood
      ratios were calculated based on the best cutoff points of the ROC curves.
      RESULTS: We enrolled 73 children, and 49 children met eligibility criteria. Based
      on our gold standard, the children had a mean percent dehydration of 5% on
      arrival. The WHO scale, Gorelick scale, and CDS did not have an area under the
      ROC curve statistically different from the reference line. The WHO scale had
      sensitivities of 79% and 50% and specificities of 43% and 61% for severe and
      moderate dehydration, respectively; the 4- and 10-point Gorelick scale had
      sensitivities of 64% and 21% and specificities of 69% and 89%, respectively, for
      severe dehydration, while the same scales had sensitivities of 68% and 82% and
      specificities of 41% and 35% for moderate dehydration; the CDS had a sensitivity
      of 68% and specificity of 45% for moderate dehydration. CONCLUSION: In this
      sample of children, the WHO scale, Gorelick scale, and CDS did not provide an
      accurate assessment of dehydration status when used by general physicians and
      nurses in a developing world setting.

PMID- 21902837
TI  - Mesenchymal stem cells: from experiment to clinic.
AB  - There is currently much interest in adult mesenchymal stem cells (MSCs) and
      their ability to differentiate into other cell types, and to partake in the
      anatomy and physiology of remote organs. It is now clear these cells may be
      purified from several organs in the body besides bone marrow. MSCs take part in
      wound healing by contributing to myofibroblast and possibly fibroblast
      populations, and may be involved in epithelial tissue regeneration in certain
      organs, although this remains more controversial. In this review, we examine the
      ability of MSCs to modulate liver, kidney, heart and intestinal repair, and we
      update their opposing qualities of being less immunogenic and therefore tolerated
      in a transplant situation, yet being able to contribute to xenograft models of
      human tumour formation in other contexts. However, such observations have not
      been replicated in the clinic. Recent studies showing the clinical safety of MSC
      in several pathologies are discussed. The possible opposing powers of MSC need
      careful understanding and control if their clinical potential is to be realised
      with long-term safety for patients.

PMID- 21902840
TI  - The prevalence of Early Childhood Caries in 1-2 yrs olds in a semi-urban area of
      Sri Lanka.
AB  - BACKGROUND: ECC remains a problem in both developed and developing countries and
      ECC has been considered to be present in epidemic proportions in the developing
      countries. The aetiology and associated factors of ECC should be studied
      adequately to overcome this health hazard. The objective of this study is to
      determine the prevalence of ECC in 1 to 2 years old children in some selected MOH
      areas (semi-urban) in the district of Colombo, Sri Lanka. METHODS: This study was
      conducted as a cross sectional study. A total of 422 children aged 1-2 years were
      selected using systematic sampling technique in Maharagama, Piliyandala, Nugegoda
      and Boralesgamuwa MOH areas in Colombo district, Western province, Sri Lanka. The
      pre-test was done initially with 10 children aged 1 1/2 year olds.Prior to the
      clinical examination of each child, a questionnaire consisting questions
      regarding tooth brushing, dietary habits, breast and bottle feeding, long term
      medications(Sweetened medications taken more than 3 months), attending a dental
      clinic during pregnancy of mother and socio-economical status of the family was
      administered to mothers of those children. Sterile dental mouth mirrors were used
      to detect ECC in children. RESULTS: The prevalence of ECC of the whole sample of
      410 children aged 1-2 years was 32.19% and the mean dmft was 2.01 and the mean
      dmfs was 3.83. From the children who had ECC 95% were untreated. There were
      significant relationships between dmft and long term use of medications (p <
      0.000), intake of sugar with milk (p = 0.013), sweet consumption (p = 0.013),
      employment of mothers (p < 0.000) and visiting a dental clinic during pregnancy
      (p < 0.000). CONCLUSIONS: This study documents high prevalence and severity of
      ECC among 1-2 years old children in four selected MOH areas of Colombo district
      and caries in most of the children with ECC (95%) were untreated. Results reveal
      an urgent need to increase awareness among the public about ECC and institute
      preventive strategies.

PMID- 21902841
TI  - Epidemiological characteristics of Candida species colonizing oral and rectal
      sites of Jordanian infants.
AB  - BACKGROUND: There is evidence that Candida colonization contributes to increasing
      invasion of candidiasis in hospitalized neonates. Few studies investigated the
      epidemiology and risk factors of Candida colonization among hospitalized and non
      hospitalized infants. This prospective study investigated the major
      epidemiological characteristics of Candida species colonizing oral and rectal
      sites of Jordanian infants. METHODS: Infants aged one year or less who were
      examined at the pediatrics outpatient clinic or hospitalized at the Jordan
      University Hospital, Amman, Jordan, were included in this study. Culture swabs
      were collected from oral and rectal sites and inoculated on Sabouraud dextrose
      agar. All Candida isolates were confirmed by the Remel RapID yeast plus system,
      and further investigated for specific virulence factors and antifungal
      susceptibility MIC using E-test. Genotyping of C. albicans isolates was
      determined using random amplified polymorphic DNA (RAPD) analysis method.
      RESULTS: A total of 61/492 (12.4%) infants were colonized with Candida species by
      either their oral/rectal sites or both. Rectal colonization was significantly
      more detected than oral colonization (64.6% verses 35.4%), particularly among
      hospitalized infants aged more than one month. The pattern and rates of
      colonization were as follows: C. albicans was the commonest species isolated from
      both sites and accounted for 67.1% of all isolates, followed by C.kefyr (11.4%),
      each C. tropicalis and C. glabrata (8.9%) and C. parapsilosis (3.8%). A various
      rates of Candida isolates proved to secrete putative virulence factors in vitro;
      asparatyl proteinase, phospholipase and hemolysin. C. albicans were associated
      significantly (P < 0.05) with these enzymes than other Candida species. All
      Candida isolates were susceptible to amphotericin B and caspofungin, whereas 97%
      of Candida species isolates were susceptible to fluconazole using E-test. The
      genetic similarity of 53 C. albicans isolates as demonstrated by dendrogram
      revealed the presence of 29 genotypes, and of these one genotype accounted for
      22% of the isolates. CONCLUSION: This study presents important epidemiological
      features of Candida colonization of Jordanian infants.

PMID- 21902842
TI  - MiR-206-mediated dynamic mechanism of the mammalian circadian clock.
AB  - BACKGROUND: As a group of highly conserved small non-coding RNAs with a length of
      21~23 nucleotides, microRNAs (miRNAs) regulate the gene expression post
      transcriptionally by base pairing with the partial or full complementary
      sequences in target mRNAs, thus resulting in the repression of mRNA translation
      and the acceleration of mRNA degradation. Recent work has revealed that miRNAs
      are essential for the development and functioning of the skeletal muscles where
      they are. In particular, miR-206 has not only been identified as the only miRNA
      expressed in skeletal muscles, but also exhibited crucial roles in regulation of
      the muscle development. Although miRNAs are known to regulate various biological
      processes ranging from development to cancer, much less is known about their role
      in the dynamic regulation of the mammalian circadian clock. RESULTS: A detailed
      dynamic model of miR-206-mediated mammalian circadian clock system was developed
      presently by using Hill-type terms, Michaelis-Menten type and mass action
      kinetics. Based on a system-theoretic approach, the model accurately predicts
      both the periodicity and the entrainment of the circadian clock. It also explores
      the dynamics properties of the oscillations mediated by miR-206 by means of
      sensitivity analysis and alterations of parameters. Our results show that miR-206
      is an important regulator of the circadian clock in skeletal muscle, and thus by
      study of miR-206 the main features of its mediation on the clock may be captured.
      Simulations of these processes display that the amplitude and frequency of the
      oscillation can be significantly altered through the miR-206-mediated control.
      CONCLUSIONS: MiR-206 has a profound effect on the dynamic mechanism of the
      mammalian circadian clock, both by control of the amplitude and control or
      alteration of the frequency to affect the level of the gene expression and to
      interfere with the temporal sequence of the gene production or delivery. This
      undoubtedly uncovers a new mechanism for regulation of the circadian clock at a
      post-transcriptional level and provides important insights into the normal
      development as well as the pathological conditions of skeletal muscles, such as
      the aging, chronic disease and cancer.

PMID- 21902843
TI  - A combined functional and structural genomics approach identified an EST-SSR
      marker with complete linkage to the Ligon lintless-2 genetic locus in cotton
      (Gossypium hirsutum L.).
AB  - BACKGROUND: Cotton fiber length is an important quality attribute to the textile
      industry and longer fibers can be more efficiently spun into yarns to produce
      superior fabrics. There is typically a negative correlation between yield and
      fiber quality traits such as length. An understanding of the regulatory
      mechanisms controlling fiber length can potentially provide a valuable tool for
      cotton breeders to improve fiber length while maintaining high yields. The cotton
      (Gossypium hirsutum L.) fiber mutation Ligon lintless-2 is controlled by a single
      dominant gene (Li2) that results in significantly shorter fibers than a wild
      type. In a near-isogenic state with a wild-type cotton line, Li2 is a model
      system with which to study fiber elongation. RESULTS: Two near-isogenic lines of
      Ligon lintless-2 (Li2) cotton, one mutant and one wild-type, were developed
      through five generations of backcrosses (BC5). An F2 population was developed
      from a cross between the two Li2 near-isogenic lines and used to develop a
      linkage map of the Li2 locus on chromosome 18. Five simple sequence repeat (SSR)
      markers were closely mapped around the Li2 locus region with two of the markers
      flanking the Li2 locus at 0.87 and 0.52 centimorgan. No apparent differences in
      fiber initiation and early fiber elongation were observed between the mutant
      ovules and the wild-type ones. Gene expression profiling using microarrays
      suggested roles of reactive oxygen species (ROS) homeostasis and cytokinin
      regulation in the Li2 mutant phenotype. Microarray gene expression data led to
      successful identification of an EST-SSR marker (NAU3991) that displayed complete
      linkage to the Li2 locus. CONCLUSIONS: In the field of cotton genomics, we report
      the first successful conversion of gene expression data into an SSR marker that
      is associated with a genomic region harboring a gene responsible for a fiber
      trait. The EST-derived SSR marker NAU3991 displayed complete linkage to the Li2
      locus on chromosome 18 and resided in a gene with similarity to a putative
      plectin-related protein. The complete linkage suggests that this expressed
      sequence may be the Li2 gene.

PMID- 21902845
TI  - [A man with a swollen scrotum].
AB  - A 32-year-old man was referred to our hospital with a painless left-sided scrotal
      mass present since infancy. Physical examination showed 2 small ovoid masses in
      the left hemiscrotum and 1 testis on the right side. Ultrasound showed a
      supernumerary testis with fusion of epididymis. The diagnosis was: polyorchidism.

PMID- 21902844
TI  - How to do a grounded theory study: a worked example of a study of dental
      practices.
AB  - BACKGROUND: Qualitative methodologies are increasingly popular in medical
      research. Grounded theory is the methodology most-often cited by authors of
      qualitative studies in medicine, but it has been suggested that many 'grounded
      theory' studies are not concordant with the methodology. In this paper we provide
      a worked example of a grounded theory project. Our aim is to provide a model for
      practice, to connect medical researchers with a useful methodology, and to
      increase the quality of 'grounded theory' research published in the medical
      literature. METHODS: We documented a worked example of using grounded theory
      methodology in practice. RESULTS: We describe our sampling, data collection, data
      analysis and interpretation. We explain how these steps were consistent with
      grounded theory methodology, and show how they related to one another. Grounded
      theory methodology assisted us to develop a detailed model of the process of
      adapting preventive protocols into dental practice, and to analyse variation in
      this process in different dental practices. CONCLUSIONS: By employing grounded
      theory methodology rigorously, medical researchers can better design and justify
      their methods, and produce high-quality findings that will be more useful to
      patients, professionals and the research community.

PMID- 21902846
TI  - [Jaundice and a pancreatic tumour caused by auto-immune pancreatitis].
AB  - Three male patients aged between 50 and 70 years were referred with jaundice and
      weight loss. Imaging showed a pancreatic mass and changes in the calibre of the
      choledochal or pancreatic duct, suggestive of malignancy. Two patients were
      operated on. One patient was considered to have an unresectable carcinoma but
      showed remarkable clinical improvement after steroids were given for his poor
      condition. In the other patient a resection was performed. Histology showed IgG4
      positive plasma cell infiltration without signs of malignancy. Eventually these
      patients were diagnosed with auto-immune pancreatitis (AIP). In the third patient
      AIP was considered beforehand and this patient was treated with steroids. He
      responded quickly both clinically and radiologically. CT imaging showed complete
      remission of the mass. AIP is a benign inflammatory process which can mimic
      pancreatic carcinoma. In doubtful cases, a short trial of steroids might be
      considered.

PMID- 21902847
TI  - [Jelgersma and his clinic].
AB  - Gerbrandus Jelgersma (1859-1942) became in 1899 the first professor of psychiatry
      at Leiden University. Until then he had been employed in psychiatric asylums,
      first as pathologist and later as managing director. His scientific work was at
      first exclusively devoted to the microscopic structure of the brain, by which he
      attempted to find correlations between structure and function. In addition he had
      a wide knowledge of psychopathology. Gradually he incorporated Freud's
      psychoanalytical doctrine in his teaching and in his therapeutic methods, but as
      a scientist he remained faithful to the morphological approach. At the age of 72
      he published a monumental atlas of the brain. In 1950 the municipal hospital in
      Leiden for short-term psychiatric treatment was named after him.

PMID- 21902848
TI  - [Complaints and illnesses in children in the Netherlands].
AB  - AIM: To provide insight into the nature, prevalence and consequences of common
      chronic health problems in children (0-18 years) in the Netherlands. DESIGN:
      Survey based on general practitioner records, population surveys and a literature
      search. METHODS: "Disorders" comprises not only illness, but also complaints,
      symptoms and health problems. The survey was restricted to chronic health
      problems (present for at least 3 months) with a prevalence of at least 1% in
      children in the Netherlands. RESULTS: The chronic diseases most frequently
      registered by general practitioners are asthma and eczema (1-year prevalence ca.
      4%), followed by abdominal pain and constipation (2%-3%) in children under the
      age of 11 years and by headache, fatigue, back pain and abdominal pain (2%-3%) in
      older children. The conditions most frequently reported in population surveys by
      children themselves or their parents are headache, fatigue and sleeping problems,
      followed by hay fever, depressive symptoms and back pain. The prevalence of such
      conditions is especially high in teenage girls: over 20% for fatigue, headache
      and sleeping problems and 5-15% for depressive symptoms, back pain and abdominal
      pain. 2%-3% of all children experience serious limitations in daily functioning
      due to a chronic health condition. In addition, 8%-9% of young children and 14%
      20% of the older children experience mild limitations. CONCLUSION: A substantial
      number of children experience limitations in daily functioning due to a chronic
      condition. Allergy-related diseases, pain and malaise complaints constitute a
      major part of childhood chronic health problems. Pain and malaise complaints
      especially remain largely invisible for health care professionals and policy
      makers. A perspective of the consequences of these ailments in the long term is
      lacking.

PMID- 21902849
TI  - [Outbreak of Shiga toxin-producing Escherichia coli and haemolytic uraemic
      syndrome].
AB  - Enterohaemorrhagic Escherichia coli (EHEC) is a group of pathogenic Shiga toxin
      producing E. coli that can cause haemorrhagic colitis and haemolytic uraemic
      syndrome (HUS). The disease usually occurs sporadically, but sometimes also
      occurs in large outbreaks such as that which recently occurred in northern
      Germany. EHEC infection is a zoonosis and its reservoir is in ruminant farm
      animals (cattle, sheep and goats). EHEC infection should be considered in
      patients with bloody diarrhoea, but in the course of many severe EHEC infections
      a picture resembling HUS may also occur. Antibiotic treatment is contraindicated
      because it does not reduce the duration of the disease and may have negative
      complications. Patients with EHEC infection may spread the bacteria and their
      care includes contact isolation measures with their own toilet facilities. The E.
      coli type O104:H4 that occurred in Germany has a combination of specific
      virulence characteristics. This outbreak affected many people who developed HUS
      and neurological symptoms following bloody diarrhoea.

PMID- 21902850
TI  - [Population-based breast cancer screening is not worthwhile. Screening has little
      effect on mortality].
AB  - Comparison of breast cancer mortality between pairs of similar countries (Sweden
      and Norway, Northern Ireland and the Irish Republic, the Netherlands and Belgium
      or Flanders), each of which had implemented its population-wide breast cancer
      screening programme at a different point in time, demonstrated little effect of
      screening on mortality. In the Netherlands, a well-organised population-wide
      screening programme was started in the early nineties, ten years before such a
      programme was introduced in Flanders. We used the 1989-1992 period as a baseline
      and compared breast cancer mortality in the Netherlands with that in Flanders
      during the 2005-2008 period. The added value of organised screening was low: 11%
      in the target age group of 55-79 years, or 180 prevented breast-cancer deaths
      annually. A total of 5000 screening mammograms were needed to prevent one death
      from breast cancer. Breast cancer screening is not a public health priority.
      Impartial and transparent information on the disadvantages and benefits of breast
      cancer screening is urgently needed.

PMID- 21902851
TI  - [Patient with haemolytic uremic syndrome and Escherichia coli (EHEC) infection].
AB  - BACKGROUND: In infection with the enterohaemorrhagic Escherichia coli (EHEC),
      toxins produced by the bacteria can induce the potentially lethal disease
      haemolytic uremic syndrome (HUS). CASE DESCRIPTION: A 71-year-old woman was seen
      at the Emergency Department with abdominal cramps and bloody diarrhoea.
      Diagnostic tests revealed ischaemia of the intestinal mucosa. A few days after
      admission the patient developed acute malfunction of the kidneys and
      thrombocytopenia. HUS was diagnosed, which was later shown to be caused by
      infection with EHEC. The patient was treated with plasmapheresis and
      haemodialysis, which brought her kidney function back to normal. History taking
      revealed that the patient had visited northern Germany where the EHEC epidemic
      was raging. CONCLUSION: In cases of bloody diarrhoea, clinicians should consider
      infection with EHEC - a bacterium for which antibiotics are not appropriate
      treatment. If the infection becomes complicated by the development of HUS, then
      the treatment of choice should be administration of fluids, and haemodialysis
      possibly combined with plasmapheresis.

PMID- 21902852
TI  - [Balancing between hope and hype in biomarker research].
AB  - Biomarkers have become a popular topic in medicine, and investigations of
      putative molecular indicators of a specific biological state have started to
      occupy a considerable part of health research. Yet only a small number of
      biomarkers are being used in routine clinical practice. Many biomarker studies
      have major methodological shortcomings, in particular in the selection of
      appropriate study groups. Strong associations cannot always be replicated in
      later research.

PMID- 21902853
TI  - Translating CBT for voices into a program for carers: a pilot study.
AB  - BACKGROUND: The treatment of persisting psychotic symptoms with cognitive
      behavioural therapy (CBTp) is now established as an evidence-based treatment;
      however its availability remains limited. We piloted a novel CBTp skills-based
      group training program for carers. The aim was to reduce service users' auditory
      hallucinations severity through carers' use of basic CBTp methods in their
      regular interactions. METHOD: Eight carer-service user dyads and one carer-carer
      service user triad participated. Carers attended the 10-week (25-hour) program,
      and completed measures of subjective burden and expressed emotion (EE) over a 30
      week period that included a baseline phase prior to the training and
      implementation phase. Service users completed weekly interviews assessing voice
      symptomatology. Analyses were conducted for each dyad using time-series methods.
      RESULTS: The training program was rated highly. Improvements in symptoms and
      carer burden ranged from none to clinically significant across different dyads.
      Carer implementation of strategies was related to reduced symptoms in one dyad;
      reductions in EE were related to symptom improvements in two dyads. CONCLUSIONS:
      There may be benefits in training carers in behavioural and cognitive management
      of persisting hallucinations. Possible mechanisms for improvements in voice
      symptomatology include reduction in carers' EE, and carer implementation of
      strategies taught.

PMID- 21902854
TI  - Applying mindfulness therapy in a group of psychotic individuals: a controlled
      study.
AB  - BACKGROUND: There are already several existing studies that show the
      effectiveness of mindfulness-based approaches in varying types of disorders. Only
      a few studies, however, have analyzed the effectiveness of this intervention in
      psychosis, and without finding, up to now, significant differences from the
      control group. AIMS: The aim of this study is two-fold: to replicate previous
      studies, and to focus on analyzing the feasibility and effectiveness of applying
      mindfulness in a group of people with psychosis. METHOD: Eighteen patients with
      psychosis were randomly assigned to experimental and control groups. The
      experimental group received eight 1-hour sessions of Mindfulness-Based Cognitive
      Therapy (MBCT), while the control group was relegated to a waiting list to
      receive MBCT therapy. RESULTS: The experimental group scored significantly higher
      than the control group in their ability to respond mindfully to stressful
      internal events. CONCLUSIONS: Both the usefulness and effectiveness of
      implementing a mindfulness-based program have been replicated in a controlled
      manner in patients with psychosis.

PMID- 21902855
TI  - Novel unsupported and empirically supported therapies: patterns of usage among
      licensed clinical social workers.
AB  - BACKGROUND: While considerable attention has been focused in recent years on
      evidence-based practice, less attention has been placed on clinical social
      workers' choice to use ineffective or harmful interventions, referred to in the
      present paper as Novel Unsupported Therapies (NUSTs). METHOD: The present study
      surveyed 400 Licensed Clinical Social Workers (LCSWs) across the United States in
      order to determine the extent of their usage of NUSTs, as well as their usage of
      conventional therapies that lacked support and empirically supported therapies
      (ESTs). Reasons for selecting interventions were also assessed. RESULTS: While
      the vast majority (97.5%) reported using some form of EST, 75% of our sample also
      reported using at least one NUST. Logistic regression analysis revealed that NUST
      usage was related to female gender and trauma specialization. A split plot ANOVA
      revealed that respondents rated positive clinical experience higher than
      published research as a reason for selecting an intervention. LCSWs with a CBT
      theoretical orientation rated research evidence more highly than those of other
      theoretical orientations. However, even within the group of LCSWs with a CBT
      orientation, clinical experience was rated more highly than research evidence.
      CONCLUSIONS: Implications for practice are discussed.

PMID- 21902856
TI  - Refeeding with a high-protein diet after a 48 h fast causes acute hepatocellular
      injury in mice.
AB  - Elucidating the effects of refeeding a high-protein diet after fasting on disease
      development is of interest in relation to excessive protein ingestion and
      irregular eating habits in developed countries. The objective of the present
      study was to address the hepatic effects of refeeding a high-protein diet after
      fasting. Mice were fasted for 48 h and then refed with a test diet containing 3,
      15, 35, 40, 45 or 50 % casein. Serum alanine aminotransferase (ALT) and aspartate
      aminotransferase (AST) activities and liver immediate-early gene expression
      levels were sequentially measured for the first 24 h after initiation of
      refeeding. Refeeding with a 50 % casein diet after 48 h of fasting led to a rapid
      (within 2-3 h) and abnormal elevation in serum ALT (P = 0.006) and AST (P =
      0.001) activities and a marked increase in liver Finkel-Biskis-Jinkins (FBJ)
      osteosarcoma oncogene (P = 0.007) and nuclear receptor subfamily 4, group A,
      member 1 (P = 0.002) mRNA levels. In contrast, refeeding of the 3, 15 or 35 %
      casein diets produced no substantial increases in serum ALT and AST activities in
      mice. Refeeding of 40, 45 or 50 % casein increased serum ALT and AST activities
      in proportion to this dietary casein content. In mice refed the 3, 15 or 35, but
      not 50 %, casein diets, liver heat shock protein 72 transcript levels greatly
      increased. We conclude from these data that the consumption of a high-protein
      diet after fasting causes acute hepatocellular injury in healthy animals, and
      propose that careful attention should be paid to the use of such diets.

PMID- 21902857
TI  - Effect of lean red meat from lamb v. lean white meat from chicken on the serum
      lipid profile: a randomised, cross-over study in women.
AB  - The main dietary guidelines recommend restricting total and saturated fat intake
      in the management of high blood cholesterol levels for cardiovascular risk. These
      recommendations are usually oversimplified by considering that all red meats
      should be limited and replaced by white meats. However, lean red meat can be as
      low in fat as white meat. We examined the effects of red meat (lean breed lamb)
      and lean white meat (chicken) intake on the lipid profile of a group of women
      with stable life conditions (nuns living in convents). An open-label, randomised,
      cross-over study was carried out in thirty-six nuns who consumed either lamb or
      chicken three times per week for 5-week periods with their usual diet. Clinical,
      dietary and biochemical variables were evaluated at baseline and the end of each
      diet period. A validated FFQ was used to assess nutrient intake and monitor
      compliance. The results showed neither between-diet differences in lipid
      responses nor differences from baseline in total cholesterol, LDL-cholesterol or
      TAG for any diet period. In conclusion, consumption of lean red meat (lamb) or
      lean white meat (chicken) as part of the usual diet is associated with a similar
      lipid response. These two foods can be exchanged in a healthy diet to increase
      palatability.

PMID- 21902858
TI  - Characteristics and nutrient intake of Taiwanese elderly vegetarians: evidence
      from a national survey.

PMID- 21902859
TI  - The proportion of lycopene isomers in human plasma is modulated by lycopene
      isomer profile in the meal but not by lycopene preparation.
AB  - Dietary lycopene consists mostly of the (all-E) isomer. Upon absorption, (all-E)
      lycopene undergoes isomerisation into various (Z)-isomers. Because these isomers
      offer potentially better health benefits than the (all-E) isomer, the aim of the
      present study was to investigate if the profile of lycopene isomers in intestinal
      lipoproteins is affected by the profile of lycopene isomers in the meal and by
      the tomato preparation. Six postprandial, crossover tests were performed in
      healthy men. Three meals provided about 70 % of the lycopene as (Z)-isomers,
      either mainly as 5-(Z) or 13-(Z), or as a mixture of 9-(Z) and 13-(Z) lycopene,
      while three tomato preparations provided lycopene mainly as the (all-E) isomer.
      Consumption of the 5-(Z) lycopene-rich meal led to a high (60 %) proportion of
      this isomer in TAG-rich lipoproteins (TRL), indicating a good absorption and/or a
      low intestinal conversion of this isomer. By contrast, consumption of meals rich
      in 9-(Z) and 13-(Z) lycopene isomers resulted in a low level of these isomers but
      high amounts of the 5-(Z) and (all-E) isomers in TRL. This indicates that the 9
      (Z) and 13-(Z) isomers were less absorbed or were converted into 5-(Z) and (all
      E) isomers. Dietary (Z)-lycopene isomers were, therefore, differently isomerised
      and released in TRL during their intestinal absorption in men. Consuming the
      three meals rich in (all-E) lycopene resulted in similar proportions of lycopene
      isomers in TRL: 60 % (all-E), 20 % 5-(Z), 9 % 13-(Z), 2 % 9-(Z) and 9 %
      unidentified (Z)-isomers. These results show that the tomato preparation has no
      impact on the lycopene isomerisation occurring during absorption in humans.

PMID- 21902860
TI  - Lactate and the GPR81 receptor in metabolic regulation: implications for adipose
      tissue function and fatty acid utilisation by muscle during exercise.
AB  - Lactate is increasingly recognised to be more than a simple end product of
      anaerobic glycolysis. Skeletal muscle and white adipose tissue are considered to
      be the main sites of lactate production and release. Recent studies have
      demonstrated that there is a specific G-protein coupled receptor for lactate,
      GPR81, which is expressed primarily in adipose tissue, and also in muscle.
      Lactate inhibits lipolysis in adipose tissue by mediating, through GPR81, the
      anti-lipolytic action of insulin. A high proportion (50 % or more) of the glucose
      utilised by white adipose tissue is converted to lactate and lactate production
      by the tissue increases markedly in obesity; this is likely to reflect a switch
      towards anaerobic metabolism with the development of hypoxia in the tissue.
      During exercise, there is a shift in fuel utilisation by muscle from lipid to
      carbohydrate, but this does not appear to be a result of the inhibition of
      lipolysis in the main adipose tissue depots by muscle-derived lactate. It is
      suggested instead that a putative autocrine lactate loop in myocytes may regulate
      fuel utilisation by muscle during exercise, operating via a muscle GPR81
      receptor. In addition to being an important substrate, lactate is a key signal in
      metabolic regulation.

PMID- 21902861
TI  - The Hospital Dementia Services Project: age differences in hospital stays for
      older people with and without dementia.
AB  - BACKGROUND: People with dementia may have adverse outcomes following periods of
      acute hospitalization. This study aimed to explore the effects of age upon
      hospitalization outcomes for patients with dementia in comparison to patients
      without dementia. METHODS: Data extracted from the New South Wales Admitted
      Patient Care Database for people aged 50 years and over for the period July 2006
      to June 2007 were linked to create person-based records relating to both single
      and multiple periods of hospitalization. This yielded nearly 409,000 multi-day
      periods of hospitalization relating to almost 253,000 persons. Using ICD-10-AM
      codes for dementia and other principal diagnoses, the relationship between age
      and hospitalization characteristics were examined for people with and without
      dementia. RESULTS: Dementia was age-related, with 25% of patients aged 85 years
      and over having dementia compared with 0.9% of patients aged 50-54 years. People
      with dementia were more likely to be admitted for fractured femurs, lower
      respiratory tract infections, urinary tract infections and head injuries than
      people without dementia. Mean length of stay for admissions for people with
      dementia was 16.4 days and 8.9 days for those without dementia. People with
      dementia were more likely than those without to be re-admitted within three
      months for another multi-day stay. Mortality rates and transfers to nursing home
      care were higher for people with dementia than for people without dementia. These
      outcomes were more pronounced in younger people with dementia. CONCLUSION:
      Outcomes of hospitalization vary substantially for patients with dementia
      compared with patients without dementia and these differences are frequently most
      marked among patients aged under 65 years.

PMID- 21902862
TI  - Comparison of behavioral and psychological symptoms of dementia and psychotropic
      drug treatments among old people in geriatric care in 2000 and 2007.
AB  - BACKGROUND: Behavioral and psychological symptoms, such as verbal or physical
      aggression, aberrant motor behaviors, psychotic symptoms, anxiety, depressive
      symptoms and apathy are common among people with dementia. The aim of the present
      study was to compare the one-week prevalence of behavioral and psychological
      symptoms and psychotropic drug treatment among people with cognitive impairment
      living in institutional care, in two large, comparable samples from 2000 and
      2007. METHODS: A comparison was made between two cross-sectional samples,
      collected in 2000 and 2007, comprising 4054 participants with cognitive
      impairment living in geriatric care units in the county of Vasterbotten, Sweden.
      The Multi-Dimensional Dementia Assessment Scale (MDDAS) was used to assess
      cognitive impairment and behavioral and psychological symptoms. The use of
      psychotropic drugs was recorded. RESULTS: Between 2000 and 2007, 15 out of 39
      behavioral or psychological symptoms had become less common and no symptoms had
      become more common, after controlling for demographic changes. Four out of six
      behaviors within the cluster of aggressive behaviors had declined in prevalence.
      Patients prescribed anti-dementia drugs increased from 5.1% to 18.0% and
      antidepressant drug use increased from 43.2% to 49.1%, while anxiolytic,
      hypnotic, sedative and antipsychotic drug use remained largely unchanged.
      CONCLUSION: The prevalence of many behavioral symptoms had declined from 2000 to
      2007, and among these changes, the decline in aggressive behaviors probably has
      the greatest clinical impact.

PMID- 21902863
TI  - Continuous use of antipsychotics and its association with mortality and
      hospitalization in institutionalized Chinese older adults: an 18-month
      prospective cohort study.
AB  - BACKGROUND: Previous meta-analyses have suggested that antipsychotics are
      associated with increased mortality in dementia patients with behavioral and
      psychological symptoms (BPSD). Subsequent observational studies, however, have
      produced conflicting results. In view of this controversy and the lack of any
      suitable pharmacological alternative for BPSD, this study aimed to investigate
      the relationship between continuous use of antipsychotics and mortality as well
      as hospitalizations in Chinese older adults with BPSD residing in nursing homes.
      METHODS: This was a prospective cohort study conducted in nursing homes in the
      Central & Western and Southern Districts of Hong Kong from July 2009 to December
      2010. Older adults were stratified into the exposed group (current users of
      antipsychotics) and control group (non-users). Demographics, comorbidity
      according to the Charlson Comorbidity Index (CCI), Barthel Index (BI(20)),
      Abbreviated Mental Test (AMT), and vaccination status for pandemic Influenza A
      (H1N1) 2009, seasonal influenza and pneumococcus were collected at baseline.
      Subjects were followed up at 18 months. All-cause mortality and all-cause
      hospitalizations were recorded. RESULTS: 599 older adults with dementia from nine
      nursing homes were recruited. The 18-month mortality rate for the exposed group
      was 24.1% while that for control group was 27.5% (P = 0.38). The exposed group
      also had a lower median rate of hospitalizations (56 (0-111) per 1000 person
      months vs 111 (0-222) per 1000 person-months, median (interquartile range),
      p<0.001). CONCLUSIONS: The continuous use of antipsychotics for BPSD does not
      increase mortality among Chinese older adults with dementia living in nursing
      homes. Furthermore, our results show that the use of antipsychotics can lead to
      decreased hospitalizations.

PMID- 21902864
TI  - Anemia and dementia among the elderly: the Sao Paulo Ageing & Health Study.
AB  - BACKGROUND: Anemia and dementia are common diseases among the elderly, but
      conflicting data are available regarding an association between these two
      conditions. We analyzed data from the Sao Paulo Ageing & Health Study to address
      the relationship between anemia and dementia. METHODS: This cross-sectional
      observational study included participants aged 65 years and older from a deprived
      area of the borough of Butantan, Sao Paulo, Brazil. Data about demographics,
      education, income, and cognitive and daily life function were collected, as well
      as blood samples. Anemia and dementia were defined according to WHO and DSM-IV
      criteria, respectively. RESULTS: Of the 2267 subjects meeting the inclusion
      criteria, 2072 agreed to participate in the study; of whom 1948 had a valid total
      blood count and were included in the analysis. Anemia was diagnosed in 203
      (10.2%) participants and dementia in 99 (5.1%). The frequency of anemia was
      higher in patients with dementia according to univariate analysis (odds ratio
      (OR) = 2.00, 95% confidence interval (CI) = 1.17-3.41, p = 0.01), but this
      association was not present after adjusting for age (OR = 1.33, 95% CI = 0.76
      2.33, p = 0.32). Further multivariate adjustment did not change the results.
      CONCLUSION: Although anemia and dementia are frequent disorders in older people,
      we found their relationship to be mediated exclusively by aging in this low
      income population from Sao Paulo.

PMID- 21902865
TI  - Which categories of social and lifestyle activities moderate the association
      between negative life events and depressive symptoms among community-dwelling
      older adults in Japan?
AB  - BACKGROUND: Social and lifestyle activities may serve as potential moderators of
      the association between negative life events (NLEs) and depressive symptoms among
      older adults. In this study, we examined whether social and lifestyle activities
      moderate the association between NLEs and depressive symptoms among older adults,
      and which activities are significant moderators. METHODS: The data came from a
      community-based sample of non-institutionalized adults aged 65 years or older. Of
      the 731 eligible older adults, 682 completed the Japanese version of the 30-item
      Geriatric Depression Scale. We measured 15 specific negative life events as well
      as 17 social and lifestyle activities which were grouped into four categories.
      RESULTS: Specific NLEs pertaining to human relationships, physical condition and
      financial status were all or were mostly associated with depressive symptoms.
      Significant moderating roles of social and lifestyle activities on the
      association of NLEs with depressive symptoms were observed between "loss of a
      significant other" and "contact with family members and friends" (beta = -0.282,
      SE = 0.091, p = 0.002); "change in human relationships" and "contact with family
      members and friends" (beta = -0.270, SE = 0.137, p = 0.048); and "change in human
      relationships" and "community involvement" (beta = -0.344, SE = 0.133, p =
      0.010). CONCLUSIONS: The most statistically significant variable moderating the
      associations between negative life events and depressive symptoms was "having
      frequent contact with family members". Depressive symptoms arising from
      troublesome interpersonal relationships in one's proximal network might be
      moderated by positive interpersonal relationships.

PMID- 21902866
TI  - Month of birth, socioeconomic background and height in rural Chinese men.
AB  - This study examines the effects of birth month and socioeconomic factors on
      height in rural Chinese men. The analysis of sample data of 833 adult men, 18-52
      years of age, collected from 600 families in rural Hebei in 2005, shows that
      adult men born in winter months (November to January) are, on average, 1.04 cm
      shorter (p<0.01) than those born during the rest of the year. In addition to the
      conventional OLS regression models, the household fixed and random effects models
      also indicate that the month-of-birth effect exists when socioeconomic variables
      are controlled for. The birth-month effect on height is, however, smaller than
      effects of socioeconomic variables, including the household registration status,
      household economy and father's class status.

PMID- 21902867
TI  - Application of colloidal palladium nanoparticles for labeling in electron
      microscopy.
AB  - The application of palladium nanoparticles as electron-dense markers for labeling
      in both transmission and scanning electron microscopy requires their conjugation
      to a specific protein. The conjugation protocol described here includes the
      dihydrolipoic acid (DHLA) capping of Pd nanoparticles (8 nm equivalent diameter)
      and their subsequent covalent attachment to functional protein molecules such as
      streptavidin, protein A, or avidin. The single-step reaction was mediated using
      the cross-linking agent ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). The
      final Pd conjugates were fully functional, as demonstrated by labeling of
      ultrathin resin sections of either bovine serum albumin or secretory granules of
      the salivary gland isolated from the partially fed female Ixodes ricinus tick.
      The results of bovine serum labeling were quantified, statistically evaluated,
      and compared with results obtained using commercially available gold particle
      conjugates (10 nm diameter). The highest values of labeling density were achieved
      using both streptavidin-Pd (106 +/- 7 particles/MUm2) and protein A-Au conjugates
      (130 +/- 18 particles/MUm2) compared to a commercial streptavidin-Au (66 +/- 16
      particles/MUm2) and protein A-Pd conjugates (70 +/- 11 particles/MUm2). The
      concentrations of both DHLA and EDC, pH during conjugation, and finally thorough
      washing away of unbound proteins crucially influenced conjugation.

PMID- 21902868
TI  - The interplay between Leishmania promastigotes and human Natural Killer cells in
      vitro leads to direct lysis of Leishmania by NK cells and modulation of NK cell
      activity by Leishmania promastigotes.
AB  - NK cells represent one of the first lines of defence in the immune reaction after
      invasion of Leishmania parasites. Depletion of mouse natural killer (NK) cells
      dramatically enhances susceptibility of normally resistant mice. In this study we
      evaluated the fate of NK cells and parasites after contact formation. The
      hydrophilic fluorescent dye CMFDA (chloro-methylfluorescin diacetate) that allows
      analysis of cytotoxicity in flow cytometry and microscopy was used. Furthermore,
      these findings were confirmed with scanning and transmission electron microscopy.
      Direct contact points were found between Leishmania promastigotes and naive human
      NK cells. These contacts were associated with transfer of cytosol by membrane
      bridges and cytotoxicity of NK cells against Leishmania. However, in contrast to
      other target cells which allow repeated exocytosis of lytic granules, contact
      with Leishmania causes immediate destruction of NK cells in a non-apoptotic way.
      Our results give a reasonable explanation for ex vivo observations of reduced NK
      cell numbers and impaired NK response in patients with acute cutaneous
      leishmaniasis. Animal models have clearly shown that NK cells play a key role in
      the induction and direction of the immune response. Thus inhibition of NK cells
      at the onset of infection would be advantageous for the survival of the parasite.

PMID- 21902869
TI  - The efficacy of novel arylimidamides against Trypanosoma cruzi in vitro.
AB  - The present study aimed to determine the in vitro biological efficacy and
      selectivity of 7 novel AIAs upon bloodstream trypomastigotes and intracellular
      amastigotes of Trypanosoma cruzi. The biological activity of these aromatic
      compounds was assayed for 48 and 24 h against intracellular parasites and
      bloodstream forms of T. cruzi (Y strain), respectively. Additional assays were
      also performed to determine their potential use in blood banks by treating the
      bloodstream parasites with the compounds diluted in mouse blood for 24 h at 4
      degrees C. Toxicity against mammalian cells was evaluated using primary cultures
      of cardiac cells incubated for 24 and 48 h with the AIAs and then cellular death
      rates were determined by MTT colorimetric assays. Our data demonstrated the
      outstanding trypanocidal effect of AIAs against T. cruzi, especially DB1853,
      DB1862, DB1867 and DB1868, giving IC50 values ranging between 16 and 70 nanomolar
      against both parasite forms. All AIAs presented superior efficacy to benznidazole
      and some, such as DB1868, also demonstrated promising activity as a candidate
      agent for blood prophylaxis. The excellent anti-trypanosomal efficacy of these
      novel AIAs against T. cruzi stimulates further in vivo studies and justifies the
      screening of new analogues with the goal of establishing a useful alternative
      therapy for Chagas disease.

PMID- 21902870
TI  - Diversity, distribution and biogeographical origins of Plasmodium parasites from
      the New Zealand bellbird (Anthornis melanura).
AB  - Understanding the origin of invasive parasites and ecological transmission
      barriers on the distribution of mosquito-borne pathogens is enriched by molecular
      phylogenetic approaches now that large databases are becoming available. Here we
      assess the biogeographical relationships among haemosporidian blood parasites and
      an avian host, the New Zealand bellbird (Meliphagidae, Anthornis melanura). Four
      Plasmodium haplotypes were identified among 93 infected bellbirds (693 screened)
      using nested PCR of a mitochondrial DNA cytochrome b gene fragment. The most
      common lineage, LIN1 (11%), is confined to northern New Zealand and falls within
      a known clade of Plasmodium (subgenus Novyella) sp. infecting Australian
      meliphagids. LIN1 differs within that clade by 4 9% sequence divergence
      suggestive of an endemic lineage to New Zealand. The most widespread lineage,
      LIN2 (2%), is an exact match with a global cosmopolitan (P. elongatum GRW06). Two
      rare lineages, LIN3 and LIN4 are less abundant, geographically restricted within
      New Zealand and have <1% sequence divergence with P. (Novyella) sp. (AFTRU08) and
      P. relictum (LINOLI01) documented from Africa. For the first time, we provide
      invaluable information on possible rates of entry of invading parasites in New
      Zealand and their distribution from temperate to cold environments.

PMID- 21902871
TI  - Involvement of sulfated glycosaminoglycans on the development and attachment of
      Trypanosoma cruzi to the luminal midgut surface in the vector, Rhodnius prolixus.
AB  - In the present study, we investigated the involvement of sulfated
      glycosaminoglycans in both the in vivo development and adhesion of T. cruzi
      epimastigotes to the luminal surface of the digestive tract of the insect vector,
      Rhodnius prolixus. Pre-incubation of T. cruzi, Dm 28c epimastigotes with heparin,
      chondroitin 4-sulfate, chondroitin 6-sulfate or protamine chloridrate inhibited
      in vitro attachment of parasites to the insect midgut. Enzymatic removal of
      heparan sulfate moieties by heparinase I or of chondroitin sulfate moieties by
      chondroitinase AC from the insect posterior midgut abolished epimastigote
      attachment in vitro. These treatments also reduced the labelling of anionic sites
      exposed at the luminal surface of the perimicrovillar membranes in the triatomine
      midgut epithelial cells. Inclusion of chondroitin 4-sulfate or chondroitin 6
      sulfate and to a lesser extent, heparin, in the T. cruzi-infected bloodmeal
      inhibited the establishment of parasites in R. prolixus. These observations
      indicate that sulfated glycosaminoglycans are one of the determinants for both
      adhesion of the T. cruzi epimastigotes to the posterior midgut epithelial cells
      of the triatomine and the parasite infection in the insect vector, R. prolixus.

PMID- 21902872
TI  - Toxoplasma gondii: the changing paradigm of congenital toxoplasmosis.
AB  - Researchers have learned much concerning the population biology of Toxoplasma
      gondii over the past 2 decades. It is now apparent that many atypical genotypes
      exist besides the typical 3 genotypes (type I, type II and type III) first
      described from samples from Europe and the United States. These genotypes can
      differ in pathogenicity and transmissibility from the typical genotypes that have
      been used in the majority of scientific research over the past 70 years. These
      differences impact much of what we used to believe as facts about congenital
      toxoplasmosis (CT) and will be important in developing new recommendations for
      prevention of CT and the monitoring of women at risk for developing CT. The
      present review highlights new information on T. gondii genotypes and how this
      information will change the way we convey information about CT to pregnant women,
      physicians and students.

PMID- 21902873
TI  - Emergence of ageing-related changes in insulin secretion by pancreatic islets of
      male rat offspring of mothers fed a low-protein diet.
AB  - Maternal low-protein (LP) diets programme beta-cell secretion, potentially
      altering the emergence of ageing of offspring pancreatic function. We
      hypothesised that isolated pancreatic islet beta-cell secretory responses are
      blunted in offspring exposed to LP during development and age-related reduction
      is influenced by the developmental stage of exposure to decreased nutrition. We
      studied male offspring of rats fed control (C) or LP protein (R) diets in
      pregnancy, first letter and/or lactation second letter of CC, RR, CR or RC
      groups. Serum glucose, insulin and homeostatic model assessment (HOMA) were
      measured. Pancreatic islets were isolated and in vitro insulin secretion
      quantified in low (LG - 5 mM) or high glucose (HG - 11 mM). Body weight and serum
      values between groups were similar at all ages. Insulin and HOMA rose with age
      and were highest at postnatal day (PND) 450 in all groups. At PND 36, insulin
      secretion was greatest in RR and RC. Only CC increased insulin secretion to HG.
      By PND 110, restricted groups responded less to LG but increased secretion to HG.
      By PND 450, CC offspring alone increased secretion to HG. Despite minimal
      differences in circulating insulin and glucose, reduced maternal protein intake
      affected insulin secretion at all ages. In addition, ageing reduced function in
      all R groups compared with CC by PND 110 and further by PND 450 most markedly in
      RC. We conclude that maternal LP diet during pregnancy and/or lactation impairs
      offspring insulin secretory response to a glucose challenge and alters the
      trajectory of ageing of pancreatic insulin secretion.

PMID- 21902874
TI  - In vitro culture and developmental cycle of the parasitic dinoflagellate
      Hematodinium sp. from the blue crab Callinectes sapidus.
AB  - Hematodinium is a genus of parasitic dinoflagellates whose species have caused
      significant mortalities in marine crustacean fisheries worldwide. A species of
      Hematodinium infects the blue crab, Callinectes sapidus on the eastern seaboard
      of the USA. The mode of transmission of the parasite in blue crabs is unknown. We
      established several continuous in vitro cultures of Hematodinium sp. isolated
      from the haemolymph of infected blue crabs. One isolate has been continuously
      maintained in our laboratory through serial subcultivation for over 12 months,
      and is capable of infecting new hosts when inoculated into healthy crabs. Cells
      of the parasite undergo characteristic developmental changes in vitro consistent
      with the identifiable stages of Hematodinium sp.: filamentous trophonts, amoeboid
      trophonts, arachnoid trophonts and sporonts, sporoblasts, prespores and
      dinospores (macrospores and microspores). Additionally, we describe an unusual
      shunt in the life cycle wherein presumptive schizonts derived from arachnoid
      sporonts developed into filamentous and arachnoid trophonts that can then
      initiate arachnoid sporonts in new cultures. This may explain the rapid
      proliferation of the parasite in blue crab hosts. We also found that temperature
      and light intensity affected the growth and development of the parasite in vitro.

PMID- 21902875
TI  - The Hybrid II assay: a sensitive and specific real-time hybridization assay for
      the diagnosis of Theileria parva infection in Cape buffalo (Syncerus caffer) and
      cattle.
AB  - Corridor disease is an acute, fatal disease of cattle caused by buffalo-adapted
      Theileria parva. This is a nationally controlled disease in South Africa and
      strict control measures apply for the movement of buffalo, which includes
      mandatory testing for the presence of T. parva and other controlled diseases.
      Accurate diagnosis of the T. parva carrier state in buffalo using the official
      real-time hybridization PCR assay (Sibeko et al. 2008), has been shown to be
      affected by concurrent infection with T. sp. (buffalo)-like parasites. We
      describe the Hybrid II assay, a real-time hybridization PCR method, which
      compares well with the official hybridization assay in terms of specificity and
      sensitivity. It is, however, not influenced by mixed infections of T. sp.
      (buffalo)-like parasites and is as such a significant improvement on the current
      hybridization assay.

PMID- 21902876
TI  - The looming epidemic of diabetes-associated tuberculosis: learning lessons from
      HIV-associated tuberculosis.
AB  - The prevalence of diabetes mellitus is increasing at a dramatic rate, and
      countries in Asia, particularly India and China, will bear the brunt of this
      epidemic. Persons with diabetes have a significantly increased risk of active
      tuberculosis (TB), which is two to three times higher  than in persons without
      diabetes. In this article, we argue that the epidemiological interactions and the
      effects on clinical presentation and treatment resulting from the interaction
      between diabetes and TB are similar to those observed for human immunodeficiency
      virus (HIV) and TB. The lessons  learned from approaches to reduce the dual
      burden of HIV and TB, and especially the modes of screening for the two diseases,
      can be adapted and applied to the screening, diagnosis, treatment and prevention
      of diabetes and TB. The new World Health Organization (WHO) and The Union
      Collaborative  Framework for care and control of TB and diabetes has many
      similarities to the WHO Policy on Collaborative Activities to reduce the dual
      burden of TB and HIV, and aims to guide policy makers and implementers on how to
      move forward and combat this looming dual epidemic. The response to the  growing
      HIV-associated TB epidemic in the 1980s and 1990s was slow and uncoordinated,
      despite clearly articulated warnings about the scale of the forthcoming problem.
      We must not make the same mistake with diabetes and TB. The Framework provides a
      template for action, and it is now up to donors,  policy makers and implementers
      to apply the recommendations in the field and to 'learn by doing'.

PMID- 21902877
TI  - Shading, a view from the inside.
AB  - Shape from shading arose from artistic practice, and later experimental
      psychology, but its formal structure has only been established recently by
      computer vision. Some of its algorithms have led to useful applications.
      Psychology has reversely borrowed these formalisms in attempts  to come to grips
      with shading as a depth cue. Results have been less than spectacular. The reason
      might well be that these formalisms are all based on Euclidean geometry and
      physics (radiometry), which, are the right tools in third person accounts, but
      have little relevance to first person  accounts, and thus are biologically (and
      consequently psychologically) of minor interest. We propose a formal theory of
      the shading cue in the first person account, 'a view from the inside'. Such a
      perspective is also required for autonomous robots in AI. This formalism cannot
      be based on  Euclidean geometry, nor on radiometry, but on the structure of
      pictorial space, and the structure of brightness space. The formalism, though
      different in kind, has a simple relation to the computer vision accounts. It has
      great robustness, is free from calibration issues, and allows purely  local shape
      inferences. It is especially suited to biological (and thus AI) implementation.
      We consider a number of predictions and confront them with available empirical
      evidence.

PMID- 21902878
TI  - Colour constancy as measured by least dissimilar matching.
AB  - Although asymmetric colour matching has been widely used in experiments on colour
      constancy, an exact colour match between objects lit by different chromatic
      lights is impossible to achieve. We used a modification of this technique,
      instructing our observers to establish the least dissimilar  pair of differently
      illuminated coloured papers. The stimulus display consisted of two identical sets
      of 22 Munsell papers illuminated independently by neutral, yellow, blue, green
      and red lights. The lights produced approximately the same illuminance. Four
      trichromatic observers participated  in the experiment. The proportion of exact
      matches was evaluated. When both sets of papers were lit by the same light, the
      exact match rate was 0.92, 0.93, 0.84, 0.78 and 0.76 for the neutral, yellow,
      blue, green and red lights, respectively. When one illumination was neutral and
      the other  chromatic, the exact match rate was 0.80, 0.40, 0.56 and 0.32 for the
      yellow, blue, green and red lights, respectively. When both lights were
      chromatic, the exact match rate was found to be even poorer (0.30 on average).
      Yet, least dissimilar matching was found to be rather systematic. Particularly, 
      a statistical test showed it was symmetric and transitive. The exact match rate
      was found to be different for different papers, varying from 0.99 (black paper)
      to 0.12 (purple paper). Such a variation can hardly be expected if observers'
      judgements were based on an illuminant estimate. We  argue that colour constancy
      cannot be achieved for all the reflecting objects because of mismatching of
      metamers. We conjecture that the visual system might have evolved to have colour
      constant perception for some ecologically valid objects at a cost of colour
      inconstancy for other types of  objects.

PMID- 21902879
TI  - Insight into sight, touch, taste and smell by multiple discriminations from norm.
AB  - The paper presents an innovative theory of perception of multiple features across
      and within modalities. Each step is illustrated by an aspect of data from diverse
      experiments. The theory is that a template or norm of previously configurated
      features is used to perceive an object in  a situation, such as consuming an item
      of food or drink. A mouthful usually stimulates sight first and then touch, taste
      and smell, with thermal, irritative, kinaesthetic and auditory patterns often
      also involved. The visual information also typically includes meanings of words,
      numbers and  pictures. Attended sensory and symbolic features of the situation
      are integrated by the individual into a multidimensional distance from the norm.
      Dimensions are calibrated in units of the response's discrimination between
      levels of each stimulus feature. This approach to perceptual performance  is
      expounded for sensed and/or conceived visual features of drinks and foods, and
      their tasted or smelt constituents, or felt and heard cracking during a bite. In
      addition, the conceptual process that informs an analytical judgment can
      influence another judgment. Applying the concept to a  stimulus forms a
      descriptive process. A concept may also be applied to another concept or to a
      description, giving greater depth of meaning to an integrative judgment.
      Furthermore, a description can be applied to an environmental source of
      stimulation, creating a percept that presumably is  conscious, whereas
      unconceptualised stimulation may be subconscious.

PMID- 21902880
TI  - Visual and auditory influence on perceptual stability in visual competition.
AB  - In visual competition, the perception of ambiguous visual patterns changes
      spontaneously. Although the process causing this perceptual alternation remains
      unclear, recent evidence suggests various types of non-visual influences in
      resolving visual ambiguity. In the present study, we  investigated cross-modal
      modulation of a transient stimulus on visual perceptual stability (i.e.,
      alternation frequency). Participants observed an ambiguous visual figure and
      reported their perceptual alternations. Concurrently, we presented visual and
      auditory transient events. The results  revealed that the auditory as well as
      visual transient events destabilize the current perception (i.e., they increase
      alternation frequency) around 0.5-1.5 s after the event. In addition, the
      magnitudes of auditory and visual effects were comparable and positively
      correlated within participants.  These results suggest that the visual perceptual
      stability can be under the influence of processes that are shared by different
      senses.

PMID- 21902881
TI  - Professor Leon Cintra McGlone, 1947-2009.

PMID- 21902882
TI  - Leon Cintra's contribution to the field of protein malnutrition effects on sleep
      and the brain.
AB  - On June 19 2009, everyone who knew Leon Cintra was shocked by the terrible news
      of the automobile accident that took his life. The feeling within the scientific
      community was that his passing was not only a great loss for Mexican science but
      also the loss of a beloved friend. He will be missed and forever remembered for
      his brilliant mind and noble heart. His scientific career was focused, since the
      beginning, on the study of protein malnutrition effects on brain morphometry,
      somato-sensory transmission, sleep, circadian rhythms and behavior. His findings
      showed that malnutrition has long lasting adverse effects on morphometry of
      systems involved in sleep regulation such as locus coeruleus, nucleus raphe
      dorsalis and susprachiasmatic nucleus, and on hippocampal circuit implicated in
      theta activity generation. His results on spectral analysis of electrical field
      potential at every 4 sec from 24-h baseline recording and 72-h of recovery sleep
      after total sleep deprivation or selective REM sleep deprivation demonstrated
      that protein malnutrition induced alterations on homeostatic as well as on
      circadian sleep regulation; brain oscillations and theta coherent activity
      between left and right hemisphere and between hippocampus and cerebral cortex are
      also affected by malnutrition.

PMID- 21902883
TI  - Mice undernourished before, but not after, weaning perform better in motor
      coordination and spatial learning tasks than well-fed controls.
AB  - Undernutrition of rodents has been claimed to result in long-term behavioural
      deficits in motor coordination and spatial learning ability, although the
      literature on this is somewhat conflicting. We have recently been engaged in a
      study of the effects of either pre- or post-weaning undernutrition on longevity
      in mice. As part of this ageing study, we have also assessed the effects of such
      nutritional regimes on motor coordination and spatial learning ability of mice.
      Motor coordination was tested in 21-week-old control and previously
      undernourished mice by assessing their ability to remain on a revolving drum. We
      have found that mice previously undernourished either during the pre- or post
      weaning period performed better than controls during some, but not all, of the
      test days. Spatial learning was tested in 50-58-week-old mice using the Morris
      water maze. In this instance we found that mice previously undernourished during
      the pre-weaning period performed better at this task than either controls or mice
      undernourished for a period after weaning. It seems that undernutrition during
      the pre-weaning period may, paradoxically, improve the performance of mice in
      these behavioural tasks compared to controls. Undernutrition after weaning had
      little or no effect on these behavioural measures. The exact mechanisms involved
      in causing the observed long-term changes in functional capacity due to a period
      of undernutrition from conception until weaning age of the mice in our study
      remain unknown.

PMID- 21902884
TI  - Early malnutrition predicts parent reports of externalizing behaviors at ages 9
      17.
AB  - OBJECTIVE: To determine whether externalizing behaviors are more prevalent in
      youth who have experienced an episode of malnutrition in the first year of life
      than in healthy comparison youth. METHOD: Parents of previously malnourished
      youth and a matched healthy comparison group completed a behavior rating scale
      when the youth were 9-15 years of age and again, 2 years later, when they were 11
      17 years of age. Longitudinal multiple regression analysis was applied to
      evaluate group differences adjusted for baseline age, sex, household standard of
      living, and maternal depressive symptoms. RESULTS: Early childhood malnutrition
      was associated with problems in executive functioning at both occasions.
      Malnutrition also predicted discernibly higher parent-reported levels of
      aggression toward peers at 9-15 years than at 11-17 years. These findings were
      independent of baseline age, sex, household standard of living, and maternal
      depressive symptoms. Problem behaviors in general decreased during follow-up.
      CONCLUSION: Parents report persisting problems with executive functioning through
      adolescence in youth who suffered an episode of moderate-to-severe protein-energy
      malnutrition in the first year of life, while reports of aggression, although
      more common when this cohort were younger, did not persist at follow-up.

PMID- 21902885
TI  - Time-place learning is altered by perinatal low-protein malnutrition in the adult
      rat.
AB  - Malnutrition produces changes in the central nervous system (CNS) of mammals
      during development, related to the intensity and timing of the malnutrition
      insult during the pre- or postnatal period. Protein malnutrition produces
      irreversible changes in hippocampal formation and some brain stem nuclei. The
      suprachiasmatic nucleus (SCN) is dramatically altered by low-protein diets during
      the gestational and perinatal periods. Also, it is known that circadian
      oscillators regulate physiological, behavioral, and cognitive processes and there
      is evidence that the time-place learning process exhibits a daily temporal
      distribution. The aim of this study was to determine the effects of chronic,
      prenatal, or postnatal malnutrition on daily patterns of the time-place learning
      process in the adult rat. Forty Sprague-Dawley male 90-day-old rats, were divided
      into four groups: 10 well nourished controls (Co), 10 chronically (CM), 10
      prenatally malnourished (PrM), and 10 postnatally malnourished (PtM) rats.
      Efficiency in time-place learning was tested by using a behavioral T-maze. Each
      rat was assayed for 10 trials before considering the final probe of efficiency.
      Each trial was 60 seconds long, final efficiency was measured by the amount of
      time the rat took to reach the end of an arm containing a water pot. Each rat was
      tested in 2-hour spans until completion of a full 24-hour cycle. A Cosinor
      analysis was used to evaluate acrophase and percentage of rhythmicity. The
      obtained results suggest that time-place learning process is influenced by the
      circadian clock. The severity and timing of prenatal or chronic protein
      malnutrition modifies the acrophase and rhythmicity of the learning circadian
      pattern, which can impact important cognitive functions.

PMID- 21902886
TI  - Lithium/nutrition interaction in the brain: a single lithium administration
      impairs spreading depression in malnourished, but not in well-nourished rats.
AB  - Lithium salts exert electrophysiological and behavioral effects in animals and
      humans and have been used clinically in the treatment of bipolar disorders.
      Little is known about the lithium/nutrition interaction in the developing brain.
      This work aimed to determine, in adult rats, whether treatment with a single dose
      of lithium chloride (LiCl) would influence the propagation of the brain
      excitability-related phenomenon known as cortical spreading depression (CSD).
      Male well-nourished (W; fed a lab chow diet with 22% protein; n=22) and
      previously protein-malnourished rats (M; fed a low-quality 8% protein diet;
      proteins mostly from vegetable source; n=20) were treated at 75-80 days of age
      with a single intraperitoneal injection of either 50 mg/kg LiCl (n=9 W and 10 M
      rats) or saline (n=13 W and 10 M rats). When the pups were 90-110 days, CSD was
      elicited at the frontal cortex and recorded during 4 hours at two cortical
      parietal points. In malnourished, but not in well-nourished rats, lithium
      treatment lowered CSD velocities (P < 0.05), in comparison with saline-injected
      animals. In a third group (n=23), in which the low-protein diet was
      quantitatively corrected to 22%, the lithium effect disappeared (n=12), compared
      to saline (n=11). Our results demonstrate a facilitating effect of malnutrition
      on the CSD-impairing action of a single lithium administration, suggesting a
      lithium/nutrition interaction.

PMID- 21902888
TI  - Effect on haematological and anthropometric parameters of iron supplementation in
      the first 2 years of life. Risks and benefits.
AB  - Effects of iron supplementation (IS) on haematological and anthropometric
      parameters in a cohort of 121 healthy children, followed from 6 to 24 months of
      life, in the Paediatric Department, Second University of Naples, were evaluated.
      Children were randomly segregated in four groups: (1) exclusively breast feeding
      (BF) weaned with non-iron fortified (NIF) foods, (2) BF and iron fortified
      formulas (IFF) and foods, (3) exclusively IFF and foods, (4) BF and oral iron
      supplementation (OIS). Haematological parameters (Hb, MCV, Serum ferritin and
      transferrin saturation) in addition to anthropometric measurements (length and
      weight) were obtained. Results from the study at 6, 12, 18 and 24 months showed
      significantly lower values of haematological parameters in BF infants than other
      groups and in IFF infants than in those with OIS. In contrast children with OIS
      showed significant lower length. It appears that IS may be of limited or no
      benefit for growth in non-iron deficient children.

PMID- 21902887
TI  - Prenatal protein malnutrition alters the proportion but not numbers of
      parvalbumin-immunoreactive interneurons in the hippocampus of the adult Sprague
      Dawley rat.
AB  - Prenatal protein malnutrition alters the structure and function of the adult rat
      hippocampal formation. The current study examines the effect of prenatal protein
      malnutrition on numbers of parvalbumin-immunoreactive (PV-IR) GABAergic
      interneurons, which are important for perisomatic inhibition of hippocampal
      pyramidal neurons. Brain sections from prenatally protein malnourished and
      normally nourished rats were stained for parvalbumin and PV-IR neurons were
      quantified using stereology in the dentate gyrus, CA3/2 and CA1 subfields, and
      the subiculum for both cerebral hemispheres. Results demonstrated that prenatal
      malnutrition did not affect the number of PV-IR interneurons in the hippocampus.
      Since prenatal protein malnutrition reduces total neuron numbers in the CA1
      subfield (1), this results in an altered ratio of PV-IR interneurons to total
      neuronal numbers (from 1:22.9 in controls to 1:20.5 in malnourished rats).
      Additionally, there was no hemispheric asymmetry of either PV-IR neuron numbers
      or ratio of PV-IR:total neuron numbers.

PMID- 21902889
TI  - Retrospective epidemiological study of Latin American patients with transfusional
      hemosiderosis: the first Latin American epidemiological study in iron overload-
      the RELATH study.
AB  - The retrospective epidemiological study of Latin Americans with transfusional
      hemosiderosis is the first regional patient registry to gather data regarding the
      burden of transfusional hemosiderosis and patterns of care in these patients.
      Retrospective and cross-sectional data were collected on patients >=2 years with
      selected chronic anemias and minimum 20 transfusions. In the 960 patients
      analyzed, sickle-cell disease (48.3%) and thalassemias (24.0%) were the most
      frequent underlying diagnoses. The registry enrolled 355 pediatric patients (187
      with sickle-cell disease/94 with thalassemia). Serum ferritin was the most
      frequent method used to detect iron overload. Complications from transfusional
      hemosiderosis were reported in ~80% of patients; hepatic (65.3%), endocrine
      (27.5%), and cardiac (18.2%) being the most frequent. These data indicate that
      hemoglobinopathies and complications due to transfusional hemosiderosis are a
      significant clinical problem in the Latin American population with iron overload.
      Chelation therapy is used insufficiently and has a high rate of discontinuation.

PMID- 21902890
TI  - Reduced corticosteroid use in adult patients with primary immune thrombocytopenia
      receiving romiplostim.
AB  - <title/> Adult patients with primary immune thrombocytopenia requiring first-line
      treatment typically receive corticosteroids, which are associated with low
      response rates and many potential side effects. In a retrospective analysis of
      two 6-month, placebo-controlled, phase III trials, corticosteroid use decreased
      from 30 to 26% among patients treated with the novel thrombopoietin-mimetic
      romiplostim (n = 83) and remained above 30% for placebo-treated patients (n =
      42). Moreover, compared to placebo, patients were spared 7 weeks of
      corticosteroid treatment for every 100 weeks of romiplostim treatment.
      Thereafter, corticosteroid use continued to decrease significantly, from 35 to
      20%, in patients treated with romiplostim for up to 3 years in an open-label
      extension study (n = 101), and patients were spared a further 8 weeks of
      corticosteroid treatment for each additional 100 weeks of romiplostim treatment.
      Such reductions in corticosteroids may improve health-related quality of life in
      patients with primary immune thrombocytopenia.

PMID- 21902891
TI  - Serum 25-hydroxyvitamin D levels are associated with prognosis in hematological
      malignancies.
AB  - It has been proposed that Vitamin D has a significant influence on disease
      progression in malignancy. This study aims to investigate whether serum levels of
      25-hydroxyvitamin D [25(OH)D] are associated with prognosis in patients with
      hematological malignancies. This study is based on 105 patients with
      hematological disease (acute and chronic leukemias, myelodysplastic syndromes,
      monoclonal gammapathies, and chronic lymphoid disorders), seen over a 6-months
      period. 25(OH)D deficiency (<20 ng/ml) appeared very common and an inverse
      relationship was observed between 25(OH)D levels and the response to therapy:
      lower levels being related to poorer response. In acute leukemias, a significant
      difference was noted between patients with long-term disease-free survival in
      those tested at diagnosis (P=0.001) or in those tested at the time of relapse
      (P=0.05). Similarly in patients with Philadelphia-positive leukemias, there was a
      correlation between molecular response and levels of 25(OH)D (P=0.01). Previously
      identified factors, such as age, season, gender, or nutritional index, were not
      related to circulating 25(OH)D levels. Lower levels of circulating 25(OH)D
      appeared related to a progressive stage of the disease and poor response to
      therapy, and, therefore, to the aggressiveness of the disease. It is a potential
      marker of prognosis in patients with leukemia.

PMID- 21902892
TI  - Impact of prohepcidin levels and iron parameters on early post-transplantation
      toxicities.
AB  - OBJECTIVE: Recent reports show the adverse impact of pre-transplantation iron
      overload on the outcome of haematopoietic stem cell transplantation (HSCT). We
      studied the pre-transplantation serum iron (SI) parameters including prohepcidin
      levels - a regulatory peptide of systemic iron homeostasis - and their role in
      early post-transplantation toxicities in allogeneic HSCT recipients. PATIENTS AND
      METHODS: One hundred consecutive patients [36 women and 64 men; median age 27.5
      years (range 16-63 years)] who underwent allogeneic HSCT between September 2003
      and October 2007 at Gazi University were included in the study. RESULTS: Pre
      transplantation serum prohepcidin levels did not show correlation with SI
      parameters and interleukin-6 levels (P>0.05). Prohepcidin levels were inversely
      correlated with the National Cancer Institute grade of mucositis (P=0.060),
      neutropenic fever (P<0.001), and the number of days with febrile neutropenia
      (P=0.003). SI levels were correlated with the severity of hepatotoxicity
      (P=0.015) while pre-transplantation transferrin saturation levels were positively
      correlated with the severity of hepatotoxicity (P=0.055), pulmonary toxicity
      (P=0.032), and sinusoidal obstruction syndrome (P=0.049). Pre-transplantation
      serum ferritin levels were positively correlated with the development of
      sinusoidal obstruction syndrome (P=0.010) and inversely correlated with the day
      of neutrophil engraftment (P=0.012). Overall survival was 41.26% with a median
      follow-up time of 13 months (range 0.0-60 months). Pre-transplantation serum
      prohepcidin levels and iron overload were not associated with survival in Cox
      regression analysis. CONCLUSION: Our results suggest that pre-transplantation
      iron parameters and prohepcidin levels might predict some of the early post
      transplantation toxicities, however, without an impact on overall survival.

PMID- 21902893
TI  - A clinical analysis of primary testicular diffuse large B-cell lymphoma in China.
AB  - The objective of this study was to analyze the clinical behavior and treatment
      policy of patients with primary testicular diffuse large B-cell lymphoma by
      retrospective analysis of 32 patients at our institute. All patients underwent
      orchidectomy. Anthracycline-based chemotherapy was administered to 27 patients
      (84.38%), six of whom also received rituximab; prophylactic intrathecal
      chemotherapy was given to seven patients (21.88%); and eight patients (25%)
      received prophylactic scrotal radiotherapy. Thirteen patients had relapse, among
      whom 12 cases were extranodal recurrences. Seven patients had central nervous
      system involvement, and four patients relapsed in the contralateral testis. The
      presence of B symptoms, poor Eastern Cooperative Oncology Group performance
      status, left testicular involvement, central nervous system involvement, and
      first relapse within 1 year were associated with worse progression-free survival
      using univariate analysis. Poor Eastern Cooperative Oncology Group performance
      status, left testicular involvement, and surgery alone were negative prognostic
      factors for overall survival.

PMID- 21902894
TI  - Bypassing the maturation arrest in myeloid cell line U937 by over-expression of
      microRNA-424.
AB  - Micro RNAs are a class of small non-coding RNAs which has been recently shown to
      play a crucial role in major cellular processes such as development and
      differentiation through post-transcriptional regulation. The role of these
      epigenetic elements has also been demonstrated in hematopoietic lineage
      differentiation and there is a large body of evidence that miR-424 is responsible
      for monocyte differentiation. Our goal was to examine the effect of miR-424 over
      expression on defeating the maturation blockage in monoblastic cell line U937.
      The permanent over-expression of miR-424 was established using a retroviral
      vector construct containing the precursor of miR-424 sequence. Induction of
      differentiation process was monitored by assaying changes in cell morphology, and
      expression of cell surface markers using light microscopy, quantitative RT-PCR,
      and flow cytometry for monocyte markers such as CD11b and CD14. The cells showed
      monocytic characteristics 14 days after transduction, and CD11b and CD14
      expression were significantly increased, confirmed by flow cytometry QRT-PCR and
      RT-PCR results. In conclusion, miR-424 over-expression is an effective factor in
      maturation of the monoblastic U937 cells and it has the ability of directing them
      into cells, expressing monocyte/macrophage characteristics.

PMID- 21902895
TI  - Quercetin-induced apoptosis involves increased hTERT enzyme activity of leukemic
      cells.
AB  - We aimed to examine the growth suppressive effects of quercetin on acute
      promyelocytic and lymphoblastic leukemia and chronic myeloid leukemia, and to
      find out whether the growth suppression is related to the blocking of telomerase
      enzyme activity. Cytotoxic effects of quercetin were shown by trypan blue
      analyses. Apoptotic effects of quercetin were examined by acridine orange and
      ethidium bromide staining by fluorescence microscopy. The effects of quercetin on
      telomerase enzyme activity were shown by hTERT Quantification Kit. Our results
      demonstrated that quercetin has antiproliferative and apoptotic effects on T-cell
      acute lymphoblastic leukemia (ALL), acute promyelocytic leukemia, and chronic
      myeloid leukemia (CML) cells. We also showed for the first time by this study
      that quercetin suppresses the activity of telomerase in ALL and CML cells. The
      results of this study show the importance of quercetin for its therapeutic
      potential in treatment of leukemias.

PMID- 21902896
TI  - Activated FVII levels in factor VII Padua (Arg304Gln) coagulation disorder and in
      true factor VII deficiency: a study in homozygotes and heterozygotes.
AB  - Congenital FVII deficiency is usually subdivided into two forms: type I and type
      II. Type I is characterized by a concomitant deficiency of FVII activity and FVII
      antigen (true deficiency). Type II is characterized by a discrepancy between FVII
      activity which is always low and FVII antigen which may be normal, near normal,
      or reduced. Thromboplastins of different origins may show a discrepant behaviour
      towards type II FVII deficiencies. The abnormal factor VII present in these forms
      may, in fact show, different levels of activity, according to the thromboplastin
      used in the assay system. Typical of these variants is the Arg304Gln mutation
      (know as FVII Padua). In this variant, FVII level is low when rabbit brain
      thromboplastin is used, whereas the level is perfectly normal when ox-brain
      thromboplastin is employed. Intermediate levels are obtained if human placenta or
      human recombinant is used. Since ox-brain thromboplastin is very sensitive to
      activated FVII, the normal FVII levels obtained in FVII Padua could be due to
      abnormally high circulating levels of activated FVII. The purpose of the present
      paper was to investigate the level of activated FVII present in homozygotes and
      heterozygotes with FVII Padua. For comparison, a group of patients with type I or
      'true' deficiency was also investigated. A group of 21 normal patients served as
      controls. The activated FVII level found in FVII Padua was 8.4 and 41.0 mU/ml for
      homozygotes and heterozygotes, respectively. The level found in homozygous true
      deficiency was unassayable, whereas that found in heterozygotes was 36.2 mU/ml.
      The level found in the control population was 64.9 mU/ml in agreement with other
      reports. The low levels of activated FVIIa found in homozygotes with FVII Padua
      indicate that the normal FVII activity found with ox-brain thromboplastin cannot
      be attributed to higher than normal circulating levels of FVIIa.

PMID- 21902897
TI  - Adipogenic differentiation alters the immunoregulatory property of mesenchymal
      stem cells through BAFF secretion.
AB  - Although it has been widely demonstrated that mesenchymal stem cells (MSCs) exert
      potent immunosuppressive effect, there is little information as to whether
      adipogenic-differentiated MSCs (adi-MSCs) share the same property. Here, adi-MSCs
      enhanced alloantigen or mitogen-stimulated lymphocyte proliferation, whereas
      undifferentiated MSCs (ud-MSCs) inhibited the proliferation. Transwell experiment
      showed that the stimulatory effect of adi-MSCs was cell-cell contact-independent,
      and required soluble factors. Furthermore, the supernatant of cultured adi-MSCs
      could effectively costimulate T and B-lymphocyte proliferation and activation in
      the presence of anti-CD3 and anti-mu chain treatment, respectively. Production of
      cytokines interferon-gamma and tumor necrosis factor-alpha by T cells, and Ig
      secretion by B cells also were increased by the supernatant of cultured adi-MSCs.
      Mechanism conducted showed that the mRNA and protein expression of costimulatory
      molecule B-cell activating factor (BAFF) was upregulated, and soluble BAFF was
      secreted in MSCs after adipogenic differentiation. By blocking the BAFF molecule
      with specific monoclonal antibody in the culture, T and B-lymphocyte
      proliferation and activation was stimulated by adi-MSCs or the supernatants were
      greatly reduced. In conclusion, adipogenic differentiation may alter the
      immunoregulatory property of MSCs, leading to stimulation of lymphocytes
      response. The BAFF molecule secreted by the adi-MSCs was responsible for this
      event.

PMID- 21902898
TI  - Quality improvement projects for appraisal and revalidation of general
      practitioners.

PMID- 21902899
TI  - Reinventing the doctor.

PMID- 21902900
TI  - Quality service delivery in cardiac rehabilitation: cross-cultural challenges in
      an Australian setting.
AB  - BACKGROUND: Cardiac rehabilitation is an evidence-based health service model for
      providing secondary prevention strategies following an acute cardiac event. In
      spite of the benefits of cardiac rehabilitation, there are striking cultural and
      ethnic disparities with regard to access to and usage of these programmes.
      OBJECTIVE: To investigate the challenges in providing cardiac rehabilitation to
      culturally diverse populations in Australia to inform culturally competent care.
      METHOD: This was a qualitative study using interviews with 25 health
      professionals from diverse professional and language backgrounds working in
      cardiac rehabilitation and participant observation of educational and counselling
      sessions in four cardiac rehabilitation programmes in metropolitan Sydney,
      Australia. RESULTS: Providing cardiac rehabilitation to patients from culturally
      and linguistically diverse backgrounds presented greater challenges than did
      provision to the mainstream population. These challenges resulted from the
      interaction of multiple and complex factors such as patients, providers,
      structural and organisational characteristics within the treatment setting.
      Communication issues, reconciling health messages with culturally specific issues
      such as diet, social and family structure and implementation of self-management
      strategies are significant challenges. CONCLUSION: Strategies are needed to
      overcome cross-cultural challenges and ensure effective and equitable cardiac
      rehabilitation service delivery.

PMID- 21902901
TI  - Calcium channel blocker associated lower urinary tract symptoms in males: an
      Australian retrospective observational study.
AB  - BACKGROUND: Lower urinary tract symptoms (LUTS) are common and prevalence
      increases with age. In men, voiding symptoms are more commonly encountered than
      storage symptoms. LUTS are often associated with chronic diseases but their
      pathophysiology requires further study. We aimed to determine whether calcium
      channel blockers (CCBs) worsened, improved or did not alter symptoms of urinary
      obstruction in males aged 45 years and above with medical conditions associated
      with urinary obstruction. METHODS: A cohort retrospective observational study was
      undertaken to identify the effect of the use of CCBs on LUTS in males over 45
      years of age. Participants were recruited from four community pharmacies and a
      general practitioner surgery. Eligible participants provided informed consent and
      were administered a standardised questionnaire (IPSS) to obtain information on
      LUTS and quality of life (QOL) prior to and after commencement of CCB therapy.
      RESULTS: Thirty-eight males were enrolled in the study, and their ages of ranged
      from 46.2 to 88.7 years, with the mean age being 66.9 years (95% CI: 63.9-69.9).
      The mean IPPS score prior to commencing a CCB was 3.13 (95% CI: 2.09-4.17)
      compared to 9.82 (95% CI: 7.83-11.80) whilst on the drug (P<0.001). After
      adjusting for other medications and conditions which may contribute to LUTS, and
      for the natural progression of LUTS with ageing, the change remained significant.
      The increase in IPPS score was associated with a significant decline in the
      respondents' QOL. CONCLUSION: The results of this study suggest that in middle
      aged males the introduction of a CCB may be associated with worsening of LUTS,
      and an associated decline in QOL, although this will need to be confirmed in
      large prospective studies. However, given the common use of these agents in males
      to treat a range of cardiovascular conditions, we would suggest that men
      prescribed a CCB should be questioned about urinary symptoms before and after
      commencing treatment.

PMID- 21902902
TI  - A preliminary report on the medical profile of disabled persons living in Zhabei
      District, Shanghai, Mainland China.
AB  - BACKGROUND: The prevalence of chronic diseases and their risk factors in
      different general populations are well documented, but little is known about
      disabled populations in China. AIMS: The purpose of this study is to report
      available data on the medical profile of disabled persons living in Zhabei
      District, Shanghai, Mainland China. It also aimed to explore the association
      between any medical conditions, types and severity of disabilities and socio
      demographic factors. METHODS: Nine hundred and sixty-one disabled persons
      underwent physical medical examination to identify predisposing conditions for
      chronic diseases (hypertension and elevated glucose, lipids and triglyceride
      levels) and to diagnose two common chronic diseases - heart disease and diabetes.
      Logistic regression was used to assess the influence of age, gender, disability
      type, disability severity, education level, employment status, socio-economic
      status or marital status on chronic diseases and predisposing factors. RESULTS:
      The mean age of the participants was 53 (+/-12.5) years. The most prevalent types
      of disability were physical disability (44.9%), visual impairment (28.8%) and
      intellectual disability (12.5%). Hyperlipidemia was most prevalent (17.1%),
      followed by hypertension (15.3%), heart disease (7.2%) and diabetes (6.0%). These
      conditions were not associated with the type or the severity of disability in
      this sample. Males were more likely to have hypertension (OR=1.75; 95% CI: 1.05,
      2.93) and elevated triglycerides (OR=1.84; 95% CI: 1.05, 3.20). The unemployed
      (OR=4.80, 95% CI: 1.45, 15.76) and older participants (OR=1.04, 95% CI: 1.02,
      1.07) were more likely to have elevated blood glucose levels. Divorced
      individuals were more likely to be diagnosed with heart disease (OR=3.72; 95% CI:
      1.37, 10.09) and those with better socio-economic backgrounds (OR=3.09; 95% CI:
      1.05, 9.15) and the older disabled (OR=1.08, 95% CI: 1.04, 1.12) were more likely
      to have diabetes. CONCLUSION: This preliminary study found that abnormal clinical
      findings were not related to the type or the severity of disability. Most
      abnormal findings were, however, related to increasing age, consistent with
      previous findings in the general Chinese population.

PMID- 21902903
TI  - How good is the quality of antenatal care in the Colombo district of Sri Lanka in
      diagnosing and treating anaemia?
AB  - BACKGROUND: Sri Lanka has shown relatively good maternal outcome indicators for a
      developing country. However, high maternal deaths from haemorrhage and anaemia
      raise questions about the quality of detection and treatment of anaemia at field
      antenatal clinics, which is the primary care setting for pregnant women. AIM: The
      aim of the study was to assess the quality of facilities and services and how
      satisfactory antenatal care is with regard to diagnosis and treatment of anaemia.
      METHODS: This study was set in field antenatal clinics and conducted in two
      stages based on the Lot Quality Assurance Sampling method. In the first stage 55
      antenatal clinics were selected, and in the second stage 275 pregnant women were
      recruited from these 55 clinics. Quality of services and quality of facilities
      were assessed using observation, and an interviewer administered questionnaire
      was used to measure client satisfaction. The validity of haemoglobin colour scale
      results was investigated by comparing them with results from a quality assured
      laboratory. RESULTS: Eleven health areas, other than the seven areas which had
      the haemoglobin investigated, were unacceptable as regards the quality of
      services. The quality of facilities was better than the quality of services in
      the Colombo district. Information and counselling was provided for only 4% of
      women in the clinics. The sensitivity and the specificity for the haemoglobin
      colour scale was 62% (95% CI: 52.9%-71.1%) and 86% (95% CI: 79.6%-93.0%)
      respectively. CONCLUSION: Urgent steps should be taken to improve the quality of
      care in the health areas where care is substandard, in order to reduce morbidity
      and mortality due to anaemia.

PMID- 21902904
TI  - Aspirin bleeding in perspective.
AB  - Aspirin therapy should be an adjunct to the medical management of patients who
      have had a vascular event but the role of aspirin prophylaxis in the primary
      prevention of vascular events is less clear. This benefit-versus-risk balance
      may, however, be influenced by evidence that aspirin reduces bowel cancer risk.
      Wider aspirin use could lead to more advice being sought on its use from
      community pharmacists and general practitioners. Yet 10% of those taking aspirin
      experience symptoms that negatively affect their daily quality of life. These
      symptoms, such as heartburn, may discourage more individuals from taking aspirin
      than would the risk of bleeding.

PMID- 21902905
TI  - European differences in cancer survival: report of an international symposium of
      general practitioners from three countries exploring primary and secondary care
      delay.
AB  - BACKGROUND: There are several potential delays in the cancer diagnostic pathway:
      patient delay, primary care delay and secondary care delay. People in the UK have
      poorer five-year survival from many cancers compared with people in European
      countries with similar healthcare systems. The reasons for this are not clear,
      although it has been postulated that UK patients may present with cancer at a
      later stage. We are conducting a study to investigate the feasibility of
      comparing diagnostic delays in different European countries. METHODS: (conduct of
      the symposium): A half-day, round-table symposium was convened with seven general
      practitioners (GPs) and single primary care researchers from Sweden (Malmo), the
      Netherlands (Maastricht) and Scotland (Aberdeen). In Session One the group had a
      broad-ranging discussion comparing and contrasting their different working
      contexts and how these might impact on the cancer diagnostic pathway. In Session
      Two the group considered two case studies from Scotland, applying their own local
      experience and the insights generated in Session One to identify common and
      divergent issues. When it had finished the facilitator drafted a detailed report
      of the symposium which was supported by reference to the individual participants'
      notes which had been collected at the end of the symposium. RESULTS: (consensus
      views reached): Sweden, the Netherlands and Scotland have strong traditions of
      primary care acting in a gate-keeping role. People with cancer in the three
      countries following a broadly similar cancer diagnostic pathway. In Sweden and
      the Netherlands GPs have direct unscreened access to a greater range of
      investigations than in Scotland. In Scotland there is a greater reliance on
      specialist guidelines than in the Netherlands or Sweden. Future research in the
      UK could explore the potential contribution of increased GP access to
      investigations and revised referral guidelines.

PMID- 21902906
TI  - Reducing variation in general practitioner referral rates through clinical
      engagement and peer review of referrals: a service improvement project.
AB  - BACKGROUND: General practitioner (GP) referral rates to hospital services vary
      widely, without clearly identified explanatory factors, introducing important
      quality and patient safety issues. Referrals are rising everywhere year on year;
      some of these may be more appropriately redirected to lower technology services.
      AIM: To use peer review with consultant engagement to influence GPs to improve
      the quality and effectiveness of their referrals. DESIGN: Service development
      project. SETTING: Ten out of 13 GP practices in Torfaen, Gwent; consultants from
      seven specialties in Gwent Healthcare NHS Trust; project designed and managed
      within Torfaen Local Health Board between 2008 and 2009. METHODS: GPs discussed
      the appropriateness of referrals in selected specialties, including referral
      information and compatibility with local guidelines, usually on a weekly basis
      and were provided with regular feedback of 'benchmarked' referral rates. Six
      weekly 'cluster groups', involving GPs, hospital specialists and community health
      practitioners discussed referral pathways and appropriate management in community
      based services. RESULTS: Overall there was a reduction in variation in individual
      GP referral rates (from 2.6-7.7 to 3.0-6.5 per 1000 patients per quarter) and a
      related reduction in overall referral rate (from 5.5 to 4.3 per 1000 patients per
      quarter). Both reductions appeared sustainable whilst the intervention continued,
      and referral rates rose in keeping with local trends once the intervention
      finished. CONCLUSION: This intervention appeared acceptable to GPs because of its
      emphasis on reviewing appropriateness and quality of referrals and was effective
      and sustainable while the investment in resources continued. Consultant
      involvement in discussions appeared important. The intervention's cost
      effectiveness requires evaluation for consideration of future referral management
      strategies.

PMID- 21902907
TI  - Effect of modification manner on the photodynamic antitumor activity of C60
      modified with pullulan.
AB  - To design a novel cytospecific photosensitizer for photodynamic antitumor
      therapy, a fullerene (C(60)) was chemically modified with pullulan, a water
      soluble polysaccharide with a high affinity for asialoglycoprotein receptors
      (ASGPRs). The effect of the molecular weight of pullulan and the modification
      manner to C(60) on the photodynamic antitumor activity of C(60) modified with
      pullulan was evaluated. In this study, two modification manners were selected.
      First, ethylene diamine was chemically introduced to the hydroxyl groups of
      pullulan with different molecular weights. Then, C(60) was coupled to pullulan
      through the amino groups introduced (pendant type). Second, ethylene diamine was
      introduced to the terminal aldehyde groups of pullulan by a reductive amination
      reaction, and then the pullulan with the terminal amino groups was coupled to
      C(60) (terminal type). Irrespective of the pullulan molecular and the
      modification manner, the C(60)-pullulan conjugates exhibited a similar ability to
      generate superoxide anions upon light irradiation. Comparing the C(60)-pullulan
      conjugates of pendant and terminal types, a high lectin affinity was observed for
      the latter conjugates. The conjugates showed a high affinity for HepG2 cells with
      ASGPRs and, consequently, a strong in vitro antitumor activity on the cells. It
      is concluded that the manner of pullulan modification is a key factor
      contributing to the photodynamic antitumor activity of modified C(60).

PMID- 21902908
TI  - A novel poisson distribution-based approach for testing boundaries of real-time
      PCR assays for food pathogen quantification.
AB  - The validation of quantitative real-time PCR systems and above all, proof of the
      detection limit of this method, is a frequently and intensively discussed topic
      in food pathogen detection. Among proper sample collection, assay design, careful
      experimental design, execution of real-time PCR, and data analysis, the
      validation of the method per se ensuring reliable quantification data is of prime
      importance. The purpose of this study was to evaluate a novel validation tool for
      real-time PCR assays, based on the theoretical possibility of the amplification
      of a single DNA target. The underlying mathematical basis for the work is Poisson
      distribution, which describes patterns of low particle numbers in a volume. In
      this context, we focused on the quantitative aspect of real-time PCR for the
      first time. This allowed for demonstration of the reliable amplification of a
      lone target DNA molecule and the demonstration of the distinct discrimination
      between integer molecular numbers when using low initial copy numbers. A real
      time PCR assay amplifying a 274-bp fragment of the positive regulatory protein A
      locus of Listeria monocytogenes was used for this work. Evidence for a linear
      range of quantification from a single target copy to 10 ng of target DNA was
      experimentally demonstrated, and evidence for the significance of this novel
      validation approach is presented here.

PMID- 21902909
TI  - Prevalence and molecular characterization of Escherichia coli O157:H7 by multiple
      locus variable-number tandem repeat analysis and pulsed-field gel electrophoresis
      in three sheep farming operations in California.
AB  - A year-long study was conducted to determine the fecal prevalence of Escherichia
      coli O157:H7 in three sheep ranches. Strain diversity and persistence were
      compared with multiple-locus variable-number tandem repeat analysis and pulsed
      field gel electrophoresis. Ranch C, a feedlot, consisted of young sheep raised
      predominantly on a high-grain diet. The other two sites consisted of sheep raised
      on native pasture and a combination of native and irrigated pasture. Forty fecal
      samples were collected every month from each ranch. Samples were examined for E.
      coli O157:H7 by immunomagnetic separation and culture of the magnetic beads onto
      selective media. Detection of virulence markers in positive isolates was
      determined by PCR. E. coli O157:H7 was isolated from 100 (22.7%) of 440 fecal
      samples collected from ranch C. On ranch B, 9 (1.9%) of the 480 fecal samples
      were positive for the pathogen, while none of the samples from ranch A were
      positive. On ranch C, the odds of detecting E. coli O157:H7 was 3.2 times greater
      during the warmer months compared with the cooler months of the year. There was
      no association between days spent in the feedlot and fecal prevalence of the
      pathogen (P = 0.62). Most multiple-locus variable-number tandem repeat analysis
      types were isolated only once from ranch C (14 of 23), but several strains were
      isolated over 4 to 6 months, often in many intervening negative months. This
      study revealed that the prevalence of E. coli O157:H7 can be high in some sheep
      ranches in California, especially in feedlots where young sheep are fed
      predominantly high-grain rations.

PMID- 21902910
TI  - Modeling preharvest and harvest interventions for Escherichia coli O157
      contamination of beef cattle carcasses.
AB  - Field studies evaluating the effects of multiple concurrent preharvest
      interventions for Escherichia coli O157 are logistically and economically
      challenging; however, modeling techniques may provide useful information on these
      effects while also identifying crucial information gaps that can guide future
      research. We constructed a risk assessment model with data obtained from a
      systematic search of scientific literature. Parameter distributions were
      incorporated into a stochastic Monte Carlo modeling framework to examine the
      impacts of different combinations of preharvest and harvest interventions for E.
      coli O157 on the risk of beef carcass contamination. We estimated the risk of E.
      coli O157 carcass contamination conditional on preharvest fecal prevalence
      estimates, inclusion of feed additive(s) in the diet, vaccination for E. coli
      O157, transport and lairage effects, hide intervention(s), and carcass
      intervention(s). Prevalence parameters for E. coli O157 were assumed to encompass
      potential effects of concentration; therefore, concentration effects were not
      specifically evaluated in this study. Sensitivity analyses revealed that fecal
      prevalence, fecal-to-hide transfer, hide-to-carcass transfer, and carcass
      intervention efficacy significantly affected the risk of carcass contamination
      (correlation coefficients of 0.37, 0.56, 0.58, and -0.29, respectively). The
      results indicated that combinations of preharvest interventions may be
      particularly important for supplementing harvest interventions during periods of
      higher variability in fecal shedding prevalence (i.e., summer). Further
      assessments of the relationships among fecal prevalence and concentration, hide
      contamination, and subsequent carcass contamination are needed to further define
      risks and intervention impacts for E. coli O157 contamination of beef.

PMID- 21902911
TI  - Specific expression of adherence-related genes in Escherichia coli O157:H7 strain
      EDL933 after heat treatment in ground beef.
AB  - In this study, the expression of particular stress- and virulence-associated
      genes of Escherichia coli O157:H7 strain EDL933 in ground beef was investigated
      using real-time PCR. Specific gene expression in the food matrix was found in
      combination with heat treatment. In contrast to a treatment at 37 degrees C,
      treatment at 48 degrees C for 10 min resulted in increased expression of the
      genes eae, hcpA, iha, lpfA, and toxB. Adherence to human intestinal HT-29 cells
      was enhanced in bacterial cells inoculated and heat treated in ground beef. The
      expression of gadE, which encodes a main regulator of the glutamate system of the
      acid response, was reduced under these conditions. However, expression of rpoS
      and recA, which are involved in the establishment of stress responses, and Shiga
      toxin genes was not significantly different under the same conditions.

PMID- 21902912
TI  - Inactivation of Salmonella on pecan nutmeats by hot air treatment and oil
      roasting.
AB  - Studies were done to determine the effectiveness of hot air drying, dry roasting,
      and oil roasting in killing Salmonella on pecan nutmeats. Pecan halves and pieces
      were inoculated by immersion in a five-serotype suspension of Salmonella or by
      surface application of powdered chalk containing the pathogen. Hot air treatment
      of low-moisture (2.8 to 4.1%) and high-moisture (10.5 to 11.2%) immersion
      inoculated nutmeats (initial population, 6.18 to 7.16 log CFU/g) at 120 degrees C
      for 20 min reduced the number of Salmonella by 1.18 to 1.26 and 1.89 to 2.04 log
      CFU/g, respectively. However, regardless of the moisture content, hot air
      treatment of pecan halves containing 0.77 log CFU/g at 120 degrees C for 20 min
      failed to eliminate Salmonella. Reductions were >7 log CFU/g when dry pieces were
      dry roasted at 160 degrees C for 15 min. Treatment of halves at 140 degrees C for
      20 min, 150 degrees C for 15 min, or 170 degrees C for 10 min reduced Salmonella
      by 5 log CFU/g. The pathogen was slightly more heat resistant in immersion
      inoculated nutmeats than on surface-inoculated nutmeats. Exposure of immersion
      inoculated pieces to peanut oil at 127 degrees C for 1.5 min or 132 degrees C for
      1.0 min reduced the number of Salmonella by 5 log CFU/g. Treatment of halves at
      138 degrees C for 2.0 min reduced Salmonella by 5 log CFU/g; treatment at 132
      degrees C for 2.5 to 4.0 min did not always achieve this reduction. Hot air
      treatment cannot be relied upon to reduce Salmonella by 5 log CFU/g of raw pecan
      nutmeats without changing sensory qualities. Treatment temperatures and times
      typically used to oil roast nutmeats appear to be sufficient to reduce Salmonella
      by 5 log CFU/g.

PMID- 21902913
TI  - Prevalence and antimicrobial susceptibility of major foodborne pathogens in
      imported seafood.
AB  - Seafood is a leading commodity implicated in foodborne disease outbreaks in the
      United States. Seafood importation rose dramatically in the past 3 decades and
      now contributes to more than 80% of the total U.S. seafood supply. However,
      limited data are available on the microbiological safety of imported seafood. In
      this study, we obtained a total of 171 salmon, shrimp, and tilapia samples
      imported from 12 countries in three retail stores in Baton Rouge, LA. The total
      microbial population and the prevalence and antimicrobial susceptibilities of six
      major foodborne-pathogen genera (Campylobacter, Escherichia coli, Listeria,
      Salmonella, Shigella, and Vibrio) were determined. The aerobic plate counts (APC)
      for the 171 samples averaged 4.96 log CFU/g, with samples from Chile carrying the
      highest mean APC of 6.53 log CFU/g and fresh samples having a significantly
      higher mean APC than frozen ones (P < 0.0001). There were 27 samples (15.8%) with
      unacceptable microbiological quality (APC > 7 log CFU/g). By culture, no sample
      tested positive for Campylobacter coli, Shigella, or Vibrio vulnificus.
      Campylobacter jejuni and Salmonella enterica serovar Typhimurium were each
      recovered once from farm-raised tilapia from China. By PCR, 17.5 and 32.2% of the
      samples were positive for Salmonella and Shigella, respectively. The overall
      prevalence rates of other target bacteria were low, ranging from 4.1% for
      Listeria monocytogenes to 9.4% for E. coli. All of the Vibrio parahaemolyticus
      isolates recovered were from shrimp, and 63.3% showed intermediate resistance to
      ampicillin. Both C. jejuni isolates possessed a rare resistance to gentamicin,
      while 75% of L. monocytogenes isolates were resistant to nitrofurantoin. Taken
      together, these findings suggest potential food safety hazards associated with
      imported seafood and warrant further large-scale studies.

PMID- 21902914
TI  - Development and evaluation of a loop-mediated isothermal amplification assay for
      rapid and sensitive detection of Vibrio parahaemolyticus.
AB  - Loop-mediated isothermal amplification (LAMP) assays targeting the rpoD and toxR
      genes were developed to detect Vibrio parahaemolyticus. All 78 tested V.
      parahaemolyticus strains yielded positive results within 40 min, while negative
      results were obtained for 69 strains of other organisms even at 60 min. For V.
      parahaemolyticus ATCC 17802 in pure culture, the detection limits of LAMP assays
      targeting rpoD and toxR were 3.7 and 450 CFU per test, respectively. Due to the
      higher sensitivity of rpoD-LAMP, it was further evaluated for the ability to
      detect V. parahaemolyticus in seafood samples. V. parahaemolyticus populations
      spiked in short-necked clams were enumerated by the most-probable-number (MPN)
      method combined with the rpoD-LAMP assay and the MPN method with a culture method
      using agar medium. The MPN-rpoD-LAMP method had better sensitivity and was more
      rapid than the conventional method. These results indicate that the MPN-LAMP
      assay targeting the rpoD gene is a specific, sensitive, and rapid method to
      enumerate V. parahaemolyticus organisms.

PMID- 21902915
TI  - Efficacy of a novel sanitizer composed of lactic acid and peroxyacetic acid
      against single strains of nonpathogenic Escherichia coli K-12, Listeria innocua,
      and Lactobacillus plantarum in aqueous solution and on surfaces of romaine
      lettuce and spinach.
AB  - A novel sanitizer composed of lactic acid and peroxyacetic acid (LA-PAA) was
      developed as an alternative to chlorinated water (CW) for fresh produce
      processing. Single strains of Lactobacillus plantarum, nonpathogenic Escherichia
      coli K-12, and Listeria innocua were used to demonstrate the microbial efficacy
      of LA-PAA. LA-PAA achieved a >7.8-log reduction of L. innocua and L. plantarum
      suspended in water at 4 degrees C for 20 s, and LA, PAA, and CW achieved
      reductions of 0.4, 4.8, and 2.7 log, respectively. LA-PAA, when compared with LA,
      PAA, and CW, enhanced the reduction of L. innocua attached to romaine leaves by
      >2.2 log, and improved the removal of E. coli attached to spinach leaves by >2.4
      log. The exponential improvement in the microbial efficacy of LA-PAA showed
      synergism between LA and PAA. LA-PAA microbial efficacy was inversely
      proportional to pH value and directly correlated with residence time and
      concentration. Despite an improvement in microbial reduction through the addition
      of surfactant to LA-PAA, the usage of surfactant in washing fresh produce was
      impeded by excessive foaming during actual processing. Effects of organic matter
      on the performance of LA-PAA were minimal. External sensory evaluations showed
      that LA-PAA had no negative effects on the quality of lettuce and tender leaves.
      Temperature-abuse studies demonstrated that LA-PAA reduced decay by ~50% when
      compared with CW. Overall, these results support the premise that LA-PAA has
      significant potential to be an alternative to CW for fresh produce processing.

PMID- 21902916
TI  - Inhibition of growth of pathogenic bacteria in raw milk by legume protein esters.
AB  - Protein isolates from soybean and chickpea, as well as their methylated esters,
      were tested for their inhibitory action against the propagation of pathogenic
      bacteria in raw milk during its storage either at room temperature or under
      refrigeration. Raw milk was inoculated with a mixed culture of Listeria
      monocytogenes Scott A and Salmonella enterica serovar Enteritidis strain PT4 at
      ca. 2 log CFU ml-1. Aerobic plate count, coliform count, and presumptive E. coli
      in raw milk treated with esterified legume proteins were inhibited by 2 to 3 log
      relative to a control after 6 to 8 days of storage at 4 degrees C. At room
      temperature, bacterial populations (aerobic plate count, coliform count, and
      presumptive E. coli) in raw milk treated with esterified legume proteins were
      inhibited by ca. 1.5 to 1.6 log relative to the control after 12 h.
      Supplementation of raw milk with esterified soybean protein could significantly
      inhibit the counts of the two inoculated pathogens (L. monocytogenes Scott A and
      Salmonella Enteritidis PT4), which were initially inoculated at ca. 2 log CFU ml
      1, by ca. 2.4 log and 1.6 log CFU ml-1, respectively, on day 8 of storage under
      cold conditions. Corresponding reductions amounting to 2.7 and 1.8 log CFU ml-1
      were observed after 12 h of storage at room temperature. Supplementation of raw
      milk with esterified soybean protein (0.5%) reduced the maximum level of
      titratable acidity to 0.21 and maintained the pH level at 6.4 after 8 days of
      storage under cold conditions as compared with 4 days for untreated raw milk.
      Similar results were observed when raw milk was stored at room temperature for 10
      h.

PMID- 21902917
TI  - In vitro evaluation of Lactobacillus gasseri strains of infant origin on adhesion
      and aggregation of specific pathogens.
AB  - Numerous Lactobacillus species are members of the normal healthy human intestinal
      microbiota, and members of the Lactobacillus family predominate among the current
      marketed probiotic strains. Most of the current commercial probiotic strains have
      not been selected for specific applications but rather have been chosen based on
      their technological properties. Often the ability of such strains to temporarily
      colonize the gastrointestinal tract may be lacking, and the interactions with
      intestinal microbiota are few. Furthermore, the competitive exclusion properties
      of potential probiotic bacteria are strain specific and vary greatly. Thus, it is
      highly desirable that new candidate probiotic isolates originate from the healthy
      target population. In this study, seven newly isolated strains of Lactobacillus
      gasseri originating from feces of a healthy newborn child were evaluated for
      their ability to adhere to intestinal mucus, to autoaggregate and coaggregate
      with the model pathogens Cronobacter sakazakii (ATCC 29544) and Clostridium
      difficile (1296). All the bacterial strains, single or in combination, in viable
      and nonviable forms, were able to autoaggregate. The coaggregation with C.
      sakazakii or C. difficile was higher (P < 0.05) in nonviable than in the viable
      forms. Single L. gasseri strains showed similar adhesion abilities to intestinal
      colon mucus. The seven L. gasseri strains when combined were also able to
      significantly compete with, displace, and inhibit the adhesion of C. sakazakii
      and C. difficile in the mucus model. This study demonstrates that the studied L.
      gasseri strains fulfill the basic adhesion and aggregation properties for
      probiotics and could be considered for potential future use in children.

PMID- 21902918
TI  - Quantitative analysis of mycoflora on commercial domestic fruits in Japan.
AB  - A comprehensive and quantitative analysis of the mycoflora on the surface of
      commercial fruit was performed. Nine kinds of fruits grown in Japan were tested.
      Overall fungal counts on the fruits ranged from 3.1 to 6.5 log CFU/g. The mean
      percentages of the total yeast counts were higher than those of molds in samples
      of apples, Japanese pears, and strawberries, ranging from 58.5 to 67.0%, and were
      lower than those of molds in samples of the other six fruits, ranging from 9.8 to
      48.3%. Cladosporium was the most frequent fungus and was found in samples of all
      nine types of fruits, followed by Penicillium found in eight types of fruits. The
      fungi with the highest total counts in samples of the various fruits were
      Acremonium in cantaloupe melons (47.6% of the total fungal count), Aspergillus in
      grapes (32.2%), Aureobasidium in apples (21.3%), blueberries (63.6%), and peaches
      (33.6%), Cladosporium in strawberries (38.4%), Cryptococcus in Japanese pears
      (37.6%), Penicillium in mandarins (22.3%), and Sporobolomyces in lemons (26.9%).
      These results demonstrated that the mycoflora on the surfaces of these fruits
      mainly consists of common pre- and postharvest inhabitants of the plants or in
      the environment; fungi that produce mycotoxins or cause market diseases were not
      prominent in the mycoflora of healthy fruits. These findings suggest fruits
      should be handled carefully with consideration given to fungal contaminants,
      including nonpathogenic fungi, to control the quality of fruits and processed
      fruit products.

PMID- 21902919
TI  - Inactivation of feline calicivirus as a surrogate for norovirus on lettuce by
      electron beam irradiation.
AB  - Caliciviridae, including norovirus, are considered important sources of human
      gastroenteritis. As leafy green vegetables are commonly consumed without
      additional processing, it is important to evaluate interventions to reduce the
      presence of human pathogens in these products. Feline calicivirus was used as a
      model for small round structured viruses on lettuce. The lettuce was inoculated
      by immersion to simulate contamination from irrigation or wash water. The
      inoculated lettuce was then exposed to electron beam irradiation at various dose
      levels to determine survival. The D10-value of the calicivirus on lettuce was
      determined to be 2.95 kGy. Irradiation to reduce bacterial pathogens on cut
      lettuce could also reduce the risk associated with small round structured viruses
      on lettuce.

PMID- 21902920
TI  - Evaluation of food handler practices and microbiological status of ready-to-eat
      foods in long-term care facilities in the Andalusia region of Spain.
AB  - Food safety measures in long-term care facilities (LTCFs) are being improved by
      the introduction of quality control management systems during food production and
      by the implementation of good manufacturing practices. This study was conducted
      in LTCFs (geriatric homes) in Andalusia, Spain, during 2008 and 2009 to evaluate
      sanitary conditions and the microbiological quality and safety of salads and
      cooked meat products served. A regulation-based checklist was applied to the
      evaluated centers. Samples of ready-to-eat foods (n = 60) were examined for
      mesophilic aerobic bacteria (MAB), total coliforms, coagulase-positive
      staphylococci (CPS), Escherichia coli, Listeria spp., and Salmonella. In
      parallel, food contact surfaces (working tables, cutting boards, sinks, and
      faucets) were swabbed and analyzed for MAB and Enterobacteriaceae. The air
      quality in processing rooms, near sinks, and in canteens also was measured
      through an active air sampling method for MAB and Staphyloccocus spp. The results
      obtained revealed some deficiencies regarding handling practices and sanitary
      conditions tested (i.e., use and change of gloves, hand washing, and cleanliness
      of work surfaces). The microbial safety of foods examined indicated the absence
      of pathogens. Average levels of coagulase-positive staphylococci were below 102
      CFU/g, and prevalence of E. coli was 6.3% in samples collected. Surface counts
      were higher on cutting boards and faucets, indicating insufficient cleanliness
      procedures. This study provides a descriptive analysis of the sanitary conditions
      of food service systems in LTCF, and this information can help risk managers to
      better define control measures needed to prevent foodborne infections.

PMID- 21902922
TI  - Use of geographic information systems technology to track critical health code
      violations in retail facilities available to populations of different
      socioeconomic status and demographics.
AB  - Research shows that community socioeconomic status (SES) predicts, based on food
      service types available, whether a population has access to healthy food. It is
      not known, however, if a relationship exists between SES and risk for foodborne
      illness (FBI) at the community level. Geographic information systems (GIS) give
      researchers the ability to pinpoint health indicators to specific geographic
      locations and detect resulting environmental gradients. It has been used
      extensively to characterize the food environment, with respect to access to
      healthy foods. This research investigated the utility of GIS in determining
      whether community SES and/or demographics relate to access to safe food, as
      measured by food service critical health code violations (CHV) as a proxy for
      risk for FBI. Health inspection records documenting CHV for 10,859 food service
      facilities collected between 2005 and 2008 in Philadelphia, PA, were accessed.
      Using an overlay analysis through GIS, CHV were plotted over census tracts of the
      corresponding area. Census tracts (n = 368) were categorized into quintiles,
      based on poverty level. Overall, food service facilities in higher poverty areas
      had a greater number of facilities (with at least one CHV) and had more frequent
      inspections than facilities in lower poverty areas. The facilities in lower
      poverty areas, however, had a higher average number of CHV per inspection.
      Analysis of CHV rates in census tracts with high concentrations of minority
      populations found Hispanic facilities had more CHV than other demographics, and
      Hispanic and African American facilities had fewer days between inspections. This
      research demonstrates the potential for utilization of GIS mapping for tracking
      risks for FBI. Conversely, it sheds light on the subjective nature of health
      inspections, and indicates that underlying factors might be affecting inspection
      frequency and identification of CHV, such that CHV might not be a true proxy for
      risk for FBI.

PMID- 21902921
TI  - Trends in U.S. consumers' safe handling and consumption of food and their risk
      perceptions, 1988 through 2010.
AB  - Although survey results measuring the safety of consumers' food handling and
      risky food consumption practices have been published for over 20 years,
      evaluation of trends is impossible because the designs of published studies are
      not comparable. The Food Safety Surveys used comparable methods to interview U.S.
      adults by telephone in 1988, 1993, 2001, 2006, and 2010 about food handling
      (i.e., cross-contamination prevention) and risky consumption practices (eating
      raw or undercooked foods from animals) and perceived risk from foodborne illness.
      Sample sizes ranged from 1,620 to 4,547. Responses were analyzed descriptively,
      and four indices measuring meat, chicken, and egg cross-contamination, fish cross
      contamination, risky consumption, and risk perceptions were analyzed using
      generalized linear models. The extent of media coverage of food safety issues was
      also examined. We found a substantial improvement in food handling and
      consumption practices and an increase in perceived risk from foodborne illness
      between 1993 and 1998. All indices were stable or declined between 1998 and 2006.
      Between 2006 and 2010, the two safe food handling practice indices increased
      significantly, but risk perceptions did not change, and safe consumption
      declined. Women had safer food handling and consumption practices than men. The
      oldest and youngest respondents and those with the highest education had the
      least safe food handling behaviors. Changes in safety of practices over the
      survey years are consistent with the change in the number of media stories about
      food safety in the periods between surveys. This finding suggests that increased
      media attention to food safety issues may raise awareness of food safety hazards
      and increase vigilance in food handling by consumers.

PMID- 21902923
TI  - Microbiological quality of water immersion-chilled and air-chilled broilers.
AB  - Carcass chilling during broiler processing is a critical step in preventing
      growth of pathogenic and spoilage bacteria. The objective of this study was to
      compare the microbiological quality of air- and water-chilled broiler carcasses
      processed at the same commercial facility. For each of four replications, 15
      broilers were collected from the same commercial processing line after
      evisceration, after spraying with cetylpyridinium chloride (a cationic
      disinfectant), and after air chilling or water immersion chilling (WIC). All
      carcasses were quantitatively examined for mesophilic aerobic bacteria,
      Escherichia coli, coliforms, and Campylobacter as well as for the presence of
      Salmonella and Campylobacter. No significant differences (P > 0.05) were seen
      between air and water chilling for E. coli or coliforms or for the incidence of
      Salmonella and Campylobacter. Lower numbers of Campylobacter were recovered from
      WIC than from air-chilled carcasses (P < 0.05), but the incidence of
      Campylobacter on WIC carcasses was similar, suggesting that some Campylobacter
      organisms were injured rather than killed during WIC. In-line spraying with the
      disinfectant effectively decreased the incidence of Salmonella and Campylobacter
      on prechilled carcasses; however, cells presumably injured by the sanitizer
      recovered during chilling. Therefore, on-farm intervention strategies remain
      critically important in minimizing the spread of microbial contaminants during
      processing.

PMID- 21902924
TI  - Comparison of two possible routes of pathogen contamination of spinach leaves in
      a hydroponic cultivation system.
AB  - The route of pathogen contamination (from roots versus from leaves) of spinach
      leaves was investigated with a hydroponic cultivation system. Three major
      bacterial pathogens, Escherichia coli O157:H7, Salmonella, and Listeria
      monocytogenes, were inoculated into the hydroponic solution, in which the spinach
      was grown to give concentrations of 106 and 103 CFU/ml. In parallel, the
      pathogens were inoculated onto the growing leaf surface by pipetting, to give
      concentrations of 106 and 103 CFU per leaf. Although contamination was observed
      at a high rate through the root system by the higher inoculum (106 CFU) for all
      the pathogens tested, the contamination was rare when the lower inoculum (103
      CFU) was applied. In contrast, contamination through the leaf occurred at a very
      low rate, even when the inoculum level was high. For all the pathogens tested in
      the present study, the probability of contamination was promoted through the
      roots and with higher inoculum levels. The probability of contamination was
      analyzed with logistic regression. The logistic regression model showed that the
      odds ratio of contamination from the roots versus from the leaves was 6.93, which
      suggested that the risk of contamination from the roots was 6.93 times higher
      than the risk of contamination from the leaves. In addition, the risk of
      contamination by L. monocytogenes was about 0.3 times that of Salmonella enterica
      subsp. enterica serovars Typhimurium and Enteritidis and E. coli O157:H7. The
      results of the present study indicate that the principal route of pathogen
      contamination of growing spinach leaves in a hydroponic system is from the
      plant's roots, rather than from leaf contamination itself.

PMID- 21902925
TI  - A survey of iceberg lettuce for the presence of Salmonella, Escherichia coli
      O157:H7, and Listeria monocytogenes in Japan.
AB  - No information has been available on the prevalence of pathogens in fresh produce
      in Japan. In the present study, information was collected on the occurrence of
      contamination by Salmonella, Escherichia coli O157:H7, and Listeria monocytogenes
      in iceberg lettuce in a Japanese retail store. A total of 419 samples of lettuce
      that had been harvested in different districts and/or by different producers from
      July 2008 to March 2009 were examined. A multiplex PCR method was used to
      simultaneously identify the three bacterial pathogens. No pathogenic bacteria,
      including Salmonella, E. coli O157:H7, and L. monocytogenes, were detected from
      any of the samples with this highly sensitive and validated procedure. The
      aerobic bacteria plate counts and coliform bacteria counts in lettuce throughout
      the examination period did not show any seasonal trends, and the numbers were
      comparable to those reported by others from around the world. Based on the
      results of this study, we concluded that none of the three major pathogens were
      present in this limited survey of iceberg lettuce sold by a retailer in Japan.

PMID- 21902926
TI  - Prevalence of Salmonella enterica and the hygienic indicator Escherichia coli in
      raw meat at markets in Ouagadougou, Burkina Faso.
AB  - This study investigated the hygienic status and prevalence of Salmonella and
      Escherichia coli in retail meat sold at open markets in Ouagadougou, Burkina
      Faso. A total of 150 samples of beef meat (n = 45), beef intestine (n = 45),
      mutton (n = 30), and chicken (n = 30) were collected from four local markets for
      investigation. The prevalence of Salmonella enterica subsp. enterica was 9.3%,
      and six serotypes, all previously unreported in Burkina Faso, were identified:
      Derby, Tilene, Hato, Bredeney, Agona, and Senftenberg. Most of the Salmonella
      isolates were sensitive to the 12 antimicrobial drugs tested. The prevalence of
      E. coli was 100% in all the meat types. An assessment of hygiene practices for
      the production, transportation, display, and vending of the meat revealed
      unhygienic conditions. Meat sellers had a low education level and poor knowledge
      of foodborne pathogens and their transmission routes. The findings showed that
      foodstuff handlers were in dire need of education about safe food handling
      practices.

PMID- 21902927
TI  - Reduction of Salmonella enterica, Escherichia coli O157:H7, and Listeria
      monocytogenes with electrolyzed oxidizing water on inoculated hass avocados
      (Persea americana var. Hass).
AB  - This study was intended to evaluate the bactericidal effect of electrolyzed
      oxidizing water (EOW) and chlorinated water on populations of Salmonella
      enterica, Escherichia coli O157:H7, and Listeria monocytogenes inoculated on
      avocados (Persea americana var. Hass). In the first experiment, inoculated
      avocados were treated with a water wash applied by spraying tap water containing
      1 mg/liter free chlorine for 15 s (WW); WW treatment and then spraying sodium
      hypochlorite in water containing 75 mg/liter free chlorine for 15 s (Cl75); WW
      treatment and then spraying alkaline EOW for 30 s (AkEW) and then spraying acid
      EOW (AcEW) for 15 s; and spraying AkEW and then AcEW. In another experiment, the
      inoculated avocados were treated by spraying AkEW and then AcEW for 15, 30, 60,
      or 90 s. All three pathogen populations were lowered between 3.6 and 3.8 log
      cycles after WW treatment. The application of Cl75 did not produce any further
      reduction in counts, whereas AkEW and then AcEW treatment resulted in
      significantly lower bacterial counts for L. monocytogenes and E. coli O157:H7 but
      not for Salmonella. Treatments with AkEW and then AcEW produced a significant
      decrease in L. monocytogenes, Salmonella, and E. coli O157:H7 populations, with
      estimated log reductions of 3.9 to 5.2, 5.1 to 5.9, and 4.2 to 4.9 log CFU/cm2,
      respectively. Spraying AcEW for more than 15 s did not produce any further
      decrease in counts of Salmonella or E. coli O157:H7, whereas L. monocytogenes
      counts were significantly lower after spraying AcEW for 60 s. Applying AkEW and
      then AcEW for 15 or 30 s seems to be an effective alternative to reduce bacterial
      pathogens on avocado surfaces.

PMID- 21902928
TI  - Comparison of an automated most-probable-number technique with traditional
      plating methods for estimating populations of total aerobes, coliforms, and
      Escherichia coli associated with freshly processed broiler chickens.
AB  - An instrument (TEMPO) has been developed to automate the most-probable-number
      (MPN) technique and reduce the effort required to estimate some bacterial
      populations. We compared the automated MPN technique with traditional
      microbiological plating methods and Petrifilm methods for estimating the total
      viable count of aerobic microorganisms (TVC), total coliforms (CC), and
      Escherichia coli populations (EC) on freshly processed broiler chicken carcasses
      (postchill whole carcass rinse [WCR] samples) and cumulative drip-line samples
      from a commercial broiler processing facility. Overall, 120 broiler carcasses, 36
      prechill drip-line samples, and 40 postchill drip-line samples were collected
      over 5 days (representing five individual flocks) and analyzed by the automated
      MPN and direct agar plating and Petrifilm methods. The TVC correlation
      coefficient between the automated MPN and traditional methods was very high
      (0.972) for the prechill drip samples, which had mean log-transformed values of
      3.09 and 3.02, respectively. The TVC correlation coefficient was lower (0.710)
      for the postchill WCR samples, which had lower mean log values of 1.53 and 1.31,
      respectively. Correlations between the methods for the prechill CC and EC samples
      were 0.812 and 0.880, respectively. The estimated number of total aerobes was
      generally greater than the total number of coliforms or E. coli recovered for all
      sample types (P < 2e-16). Significantly more bacteria were recovered from the
      prechill samples than from the postchill WCR or cumulative drip samples (P < 9.5e
      12 and P < 2e-16, respectively). When samples below the limit of detection were
      excluded, 92.1% of the total responses were within a single log difference
      between the traditional plating or Petrifilm methods and the automated MPN
      method.

PMID- 21902929
TI  - Microbial examination of nonheated foods served in feeding programs of elementary
      schools, Iksan City, Jeonbuk Province, Korea.
AB  - More than 90% of elementary school students in Korea have lunch provided by a
      school feeding program. This study examined nonheated foods, foods in which final
      ingredients were added after cooking ("heated/nonheated foods"), and desserts for
      microbial contamination levels and the presence of foodborne pathogens. We
      obtained a total of 77 food samples belonging to the above three groups from four
      elementary schools located in Iksan, Jeonbuk, Korea, from June to July 2010.
      Among the samples, 15% of nonheated foods and 9% of heated/nonheated foods
      contained > 6 log CFU of aerobic bacteria per g. Unacceptable coliform counts
      according to Korean national standards (3 log CFU/g) were also observed in 30,
      4.5, and 26% of nonheated foods, heated/nonheated foods, and desserts,
      respectively. The foodborne pathogens Escherichia coli O157:H7, Bacillus cereus,
      and Cronobacter sakazakii were found in two, one, and two of the total samples,
      respectively. Detection of E. coli O157:H7 indicates a low level of safety in the
      school lunches served in Korean elementary schools. To improve food safety,
      hazard analysis critical control point guidelines should be applied to school
      food service establishments to lower the microbial risks in foods served to
      children.

PMID- 21902930
TI  - Food safety objectives for Listeria monocytogenes in Spanish food sampled in
      cafeterias and restaurants.
AB  - To gain more insight into the context of food safety management by public
      administrations, food safety objectives must be studied. The Valencian
      administration quantified the prevalence of Listeria monocytogenes in cafeterias
      and restaurants in this region of Spain between 2002 and 2010. The results
      obtained from this survey are presented here for 2,262 samples of fish, salad,
      egg, cold meat, and mayonnaise dishes. Microbiological criteria defined for L.
      monocytogenes were used to differentiate acceptable and unacceptable samples;
      more than 99.9% of the samples were acceptable. These findings indicate that
      established food safety objectives are achievable, consumer health at the time of
      consumption can be safeguarded, and food safety management systems such as hazard
      analysis critical control point plans or good manufacturing practices implemented
      in food establishments are effective. Monitoring of foods and food safety is an
      important task that must continue to reduce the current L. monocytogenes
      prevalence of 0.1% in restaurant or cafeteria dishes, which could adversely
      affect consumer health.

PMID- 21902931
TI  - Investigations on the metabolism and potentially adverse effects of ethoxyquin
      dimer, a major metabolite of the synthetic antioxidant ethoxyquin in salmon
      muscle.
AB  - The feed additive ethoxyquin (EQ) is a commonly used synthetic antioxidant
      preservative in animal feeds. In farmed Atlantic salmon fillets, EQ residues are
      present, both as the parent compound and as EQ derivatives. One of the main EQ
      derivates in fish muscle is an ethoxyquin dimer (EQDM), and the potential
      toxicity of this metabolite is not known. The aim of this study was to evaluate
      the metabolism and potentially toxicological effects of EQDM. A 90-day subchronic
      exposure study with repeated dietary exposure to EQDM at 12.5 mg/kg of body
      weight per day was performed with male F344 rats. Hepatic Cyp1a1 mRNA was
      significantly reduced to <3% of the control in rats fed EQDM, and hepatic Cyp2b1
      mRNA was increased to 192%. EQDM increased Gstpi1 mRNA expression to 144% that of
      the control, but the activity level of this phase II enzyme was reduced.
      Biomarkers of liver and kidney function did indicate adverse effects of EQDM when
      F344 rats were fed 12.5 mg/kg of body weight per day. The present study revealed
      that EQDM produces responses that are comparable to those produced by the parent
      compound (EQ) in terms of activating the same enzyme systems.

PMID- 21902932
TI  - Vitamin A intoxication from reef fish liver consumption in Bermuda.
AB  - We report three historical cases of severe vitamin A intoxication in anglers who
      had consumed reef fish liver caught in Bermuda. The subsequent analyses of 35
      fish livers from seven different fish species revealed that very high
      concentrations of vitamin A exist in tropical fish liver, even in noncarnivorous
      fish species. Large variations in concentrations were observed between specimens
      and between species. The angling population and (especially) pregnant women
      should be advised of this potential health threat.

PMID- 21902933
TI  - Diagnostic laparoscopy and adhesiolysis: does it help with complex abdominal and
      pelvic pain syndrome (CAPPS) in general surgery?
AB  - Abdominal pains secondary to adhesions are a common complaint, but most surgeons
      do not perform surgery for this complaint unless the patient suffers from a bowel
      obstruction. The purpose of this evaluation was to determine if lysis of bowel
      adhesions has a role in the surgical management of adhesions for helping treat
      abdominal pain. The database of our patients with complex abdominal and pelvic
      pain syndrome (CAPPS) was reviewed to identify patients who underwent a
      laparoscopic lysis of adhesion without any organ removal and observe if they had
      a decrease in the amount of abdominal pain after this procedure. Thirty-one
      patients completed follow-up at 3, 6, 9, and 12 months. At 6, 9, and 12 months
      postoperation, there were statistically significant decreases in patients' analog
      pain scores. We concluded that laparoscopic lysis of adhesions can help decrease
      adhesion-related pain. The pain from adhesions may involve a more complex pathway
      toward pain resolution than a simple cutting of scar tissue, such as "phantom
      pain" following amputation, which takes time to resolve after this type of
      surgery.

PMID- 21902934
TI  - Anterior vaginal wall tenderness (AVWT) as a physical symptom in chronic pelvic
      pain.
AB  - BACKGROUND AND OBJECTIVES: Chronic pelvic pain is often difficult to diagnose and
      treat properly. Physicians called on to treat this problem may not be able to
      give a specific diagnosis. The aim of this study was to see whether the physical
      presence of anterior vaginal wall tenderness could help narrow down and elucidate
      diagnoses in a practice focusing on diagnosis and treatment of chronic pelvic
      pain. METHODS: The study cohort comprised 284 patients with chronic pelvic pain
      limited to gynecologic and lower urinary problems. Histories, physical
      examinations, and endoscopic procedures were performed on each patient. An
      analysis of this information was conducted. RESULTS: Of the chronic pelvic pain
      patients, 78% had endometriosis, 81% had interstitial cystitis, and 61% had both
      concurrently. The sensitivity of anterior vaginal wall tenderness (AVWT) in
      patients with interstitial cystitis was 95%, and in those with only endometriosis
      and no interstitial cystitis, the sensitivity was 17%. The positive predictive
      value for interstitial cystitis was 85%, and for endometriosis it was 67%.
      CONCLUSIONS: Examination of the anterior vaginal wall with an empty bladder at
      the initial examination can lead one to suspect interstitial cystitis and
      possibly either concomitant or singular endometriosis and allow the physician to
      approach the workup accordingly.

PMID- 21902935
TI  - Robotic tubal anastomosis: technical aspects.
AB  - OBJECTIVES: To describe the surgical technique of robotic tubal anastomosis.
      METHODS: Retrospective chart and video review of the instrumentation and
      methodology used for robotically assisted tubal anastomosis. RESULTS: All tubal
      anastomoses were performed with the use of 3 or 4 robotic arms, 3 or 4 robotic
      instruments, and 1 assistant trocar. CONCLUSIONS: Robotic technology facilitates
      the performance of robotic tubal anastomosis.

PMID- 21902936
TI  - Laparoscopic surgical management and clinical characteristics of ovarian
      fibromas.
AB  - OBJECTIVE: This study aims to analyze the clinical characteristics and diagnostic
      features of ovarian fibromas and to evaluate the efficacy and safety of
      laparoscopic surgery for ovarian fibromas. METHODS: We reviewed the records of 47
      consecutive women who underwent laparoscopic or laparotomic surgeries and whose
      final histopathological diagnoses were ovarian fibroma, cellular fibroma, or
      fibrothecoma from January 1999 to August 2010. RESULTS: During the study period,
      49 tumors were removed from 47 women including 27 ovarian fibromas, 19
      fibrothecomas, and 3 cellular fibromas. The preoperative diagnoses were ovarian
      fibroma in 25 women (53.2%) and uterine myoma in 16 women (34.0%). A high serum
      CA 125 level (>35U/mL) was observed in 15 women, and serum CA 125 level was
      significantly higher in women with ascites (P=<0.001). The tumors were removed
      surgically in all women, using the laparotomic approach in 16 women (34.0%) and
      the laparoscopic approach in 31 women (66.0%). The laparoscopic surgery had the
      advantages of shorter hospital stay and faster return of bowel activities
      compared to laparotomy. CONCLUSIONS: Ovarian fibromas are often misdiagnosed as
      uterine myomas, and sometimes mistaken for a malignant tumor of the ovary
      preoperatively. Laparoscopic surgery can be an effective and safe surgical
      approach for managing ovarian fibromas.

PMID- 21902937
TI  - Fundamentals of laparoscopic surgery: a surgical skills assessment tool in
      gynecology.
AB  - OBJECTIVE: To describe our experience with the Fundamentals of Laparoscopic
      Surgery (FLS) program as a teaching and assessment tool for basic laparoscopic
      competency among gynecology residents. METHODS: A prospective observational study
      was conducted at a single academic institution. Before the FLS program was
      introduced, baseline FLS testing was offered to residents and gynecology division
      directors. Test scores were analyzed by training level and self-reported surgical
      experience. After implementing a minimally invasive gynecologic surgical
      curriculum, third-year residents were retested. RESULTS: The pass rates for
      baseline FLS skills testing were 0% for first-year residents, 50% for second-year
      residents, and 75% for third- and fourth-year residents. The pass rates for
      baseline cognitive testing were 60% for first- and second-year residents, 67% for
      third-year residents, and 40% for fourth-year residents. When comparing junior
      and senior residents, there was a significant difference in pass rates for the
      skills test (P=.007) but not the cognitive test (P=.068). Self-reported surgical
      experience strongly correlated with skills scores (r-value=0.97, P=.0048), but
      not cognitive scores (r-value=0.20, P=.6265). After implementing a curriculum,
      100% of the third-year residents passed the skills test, and 92% passed the
      cognitive examination. CONCLUSIONS: The FLS skills test may be a valuable
      assessment tool for gynecology residents. The cognitive test may need further
      adaptation for applicability to gynecologists.

PMID- 21902938
TI  - Bilateral hand-assisted laparoscopic renal surgery in the supine position: the
      spleen at risk.
AB  - OBJECTIVE: We evaluated the safety of simultaneous bilateral renal procedures
      performed using hand-assisted laparoscopy (HAL) with the patient in the supine
      position. MATERIALS AND METHODS: After securely strapping the patient to the
      table, a hand-port device is placed via a 7-cm supraumbilical or peri-umbilical
      incision with two to four 5-mm to 12-mm trocars placed bilaterally. During a 3
      year period, 8 bilateral HAL renal operations were initiated (upper pole partial
      nephrectomies, 3 nephroureterectomies, 3 bilateral nephrectomies, and right
      nephrectomy with left adrenalectomy). RESULTS: Mean patient age was 41 years. One
      patient with ADPKD required conversion to open due to failure to progress
      secondary to excessive perirenal fat and 22-cm kidneys. The other 7 were
      completed successfully with a mean operative time of 417 minutes and mean EBL of
      336cc. Two patients received transfusions. Two small splenic lacerations, managed
      conservatively, were the only complications. CONCLUSIONS: Bilateral hand-assisted
      laparoscopic renal surgery with the patient in the supine position (rolling the
      table side to side) is feasible in the majority of patients. However, very large
      kidneys (eg, ADPKD) may be better approached with the patient in the lateral
      decubitus position or via an open subcostal incision. Importantly, the spleen
      appears to be at increased risk for capsular injury due to apparent increased
      difficulty of left colon mobilization in the "rolled" or "airplaned" supine
      position.

PMID- 21902939
TI  - Impact of obesity on early erectile function recovery after robotic radical
      prostatectomy.
AB  - BACKGROUND AND OBJECTIVE: Studies are limited regarding the impact of obesity on
      early erectile functional outcomes after robotic radical prostatectomy. Our goal
      was to determine this impact using patient-reported validated questionnaires.
      METHODS: International Index of Erectile Function (IIEF-6) scores were
      prospectively collected with institutional review board approval, for patients
      who underwent robotic radical prostatectomy with bilateral nerve sparing from
      February 2007 to October 2009. The data were categorized into nonobese and obese
      groups and subsequently into 2 subgroups based on risk for postprostatectomy
      erectile dysfunction. Low risk is preoperative IIEF-6 >=19 and high risk is IIEF
      6 <19. The groups and subgroups were compared using chi-square analysis. RESULTS:
      Of 190 consecutive patients, 67 were excluded for preoperative severe erectile
      dysfunction (IIEF-6<7), or lack of IIEF-6 scores, or both. There were 69 nonobese
      patients of which 88% were potent preoperatively and 20% regained potency at 12
      months postoperatively. Of 54 obese patients, 85% were potent preoperatively and
      25% at 12 months. There was no difference in erectile function recovery rates
      between the groups (P=0.755). In both groups, patients with low risk of
      postoperative erectile dysfunction had statistically similar postoperative mean
      IIEF-6 scores at 6 and 12 months (P=0.580 and P=0.389, respectively), and no
      difference in erectile function recovery rates existed at 12 months (P=0.735).
      CONCLUSION: Obesity has no major contribution to the rate of early erectile
      function recovery after robotic radical prostatectomy. Preoperative erectile
      function remains the determining factor in postradical prostatectomy erectile
      dysfunction.

PMID- 21902940
TI  - Laparoscopic ventriculoperitoneal shunts: benefits to resident training and
      patient safety.
AB  - BACKGROUND AND OBJECTIVES: Symptomatic hydrocephalus is a surprisingly common
      clinical condition. Neurosurgeons are expert at ventriculostomy, but minimally
      invasive peritoneal access is outside the realm of their current training. We
      have adopted a multidisciplinary approach, with general surgeons positioning the
      distal shunt. Our objective was to review this recent experience. METHODS: All
      distal shunts were placed by a single surgeon with resident assistance. After
      ventriculostomy, the shunt tubing was tunneled onto the anterior abdominal wall.
      A Veress needle was placed through the tunnel incision and the abdomen
      insufflated. A 5-mm optical access trocar and camera were introduced via a
      separate stab incision. The shunt tubing was then directed into the abdominal
      cavity using a Hickman introducer kit, with flow confirmed visually. RESULTS:
      Study patients who had between 0 and 10 previous abdominal operations received
      111 consecutive shunts. There was one intraoperative complication, a colon injury
      during trocar placement. In this case, the colotomy was repaired and the shunt
      placed in the pleural space. There were no conversions to the open abdominal
      approach. Postoperatively, there were no wound infections, no cases of shunt
      malpositioning, and there were no deaths. CONCLUSIONS: Laparoscopic placement of
      ventriculoperitoneal shunts is feasible, safe, and carries a low rate of
      complications. The value to resident education in the practice of this procedure
      has not been previously emphasized. In the era of increased awareness of patient
      safety, laparoscopic VP shunting serves as a model for accomplishing both goals
      of improved outcomes and quality surgical education.

PMID- 21902941
TI  - Laparoscopic transhiatal esophagectomy at a low-volume center.
AB  - BACKGROUND AND OBJECTIVES: Surgical treatment of esophageal cancer is associated
      with a high rate of morbidity, even in specialized centers. Minimally invasive
      esophageal resection has become increasingly feasible and is gaining popularity
      in some high-volume institutions. This study assesses the short-term outcomes of
      laparoscopic transhiatal esophagectomy performed by a single surgeon at a single
      low-volume institution over a 20-month period. METHODS: Over the study period, 16
      patients underwent laparoscopic transhiatal esophagectomy. All patients were men
      with an average age of 70 years (range, 50 to 81). RESULTS: Two patients required
      intraoperative conversion to alternative surgical techniques, 1 to an Ivor-Lewis
      esophagectomy and 1 to an open transhiatal approach. Average operative time was
      198 minutes (range, 147 to 303). Mean hospital stay was 16.7 days (range, 9 to
      30). The average number of resected lymph nodes was 11.7, and 2 patients had
      benign pathology. No deaths occurred in the 30-day postoperative period.
      CONCLUSION: Laparoscopic transhiatal esophagectomy is an advanced laparoscopic
      procedure that can be performed with equivalent morbidity and mortality by a low
      volume surgeon in a low-volume center with results comparable to those of high
      volume centers. While several authors have demonstrated a correlation between
      lower mortality rates and high-volume esophagectomy hospitals, our results
      support surgeon experience as more important than the absolute number of
      procedures performed each year.

PMID- 21902942
TI  - Safety and efficacy of single incision laparoscopic surgery for total
      extraperitoneal inguinal hernia repair.
AB  - Almost 20 years after the first laparoscopic inguinal hernia repair was
      performed, single incision laparoscopic surgery (SILSTM) is set to revolutionize
      minimally invasive surgery. However, the loss of triangulation must be overcome
      before the technique can be popularized. This study reports the first 100
      laparoscopic total extraperitoneal hernia repairs using a single incision. The
      study cohort comprised 68 patients with a mean age of 44 (range, 18 to 83): 36
      unilateral and 32 bilateral hernias. Twelve patients also underwent umbilical
      hernia repair with the Ventralex patch requiring no additional incisions. A 2.5
      cm to 3-cm crescentic incision within the confines of the umbilicus was
      performed. Standard dissecting instruments and 52-cm/5.5-mm/30(0) laparoscope
      were used. Operation times were 50 minutes for unilateral and 80 minutes for
      bilateral. There was one conversion to conventional 3-port laparoscopic repair
      and none to open surgery. Outpatient surgery was achieved in all (except one).
      Analgesic requirements were minimal: 8 Dextropropoxyphene tablets (range, 0 to
      20). There were no intraoperative or postoperative complications with a high
      patient satisfaction score. Single-incision laparoscopic hernia repair is safe
      and efficient simply by modifying dissection techniques (so-called "inline" and
      "vertical"). Comparable success can be obtained while negating the risks of bowel
      and vascular injuries from sharp trocars and achieving improved cosmetic results.

PMID- 21902943
TI  - Transanal endoscopic video-assisted excision: application of single-port access.
AB  - BACKGROUND: Transanal endoscopic microsurgery is a safe and efficacious surgical
      approach for local excision of benign adenomas and early-stage rectal cancer.
      However, utilization of the technique has been limited due to the unavailability
      of high-priced specialized instrumentation at many institutions and the
      technically demanding training required. To avoid these obstacles, we have
      explored an alternative approach called Transanal Endoscopic Video-Assisted
      excision, which combines the merits of singleport access and local transanal
      excision. METHODS: A disposable single-incision port is inserted into the anal
      canal for transanal access. The port contains 3 cannulae for introducing
      instrumentation into the rectal lumen, and a supplementary cannula for carbon
      dioxide insufflation. Pneumorectum results in rectal distention and optimizes the
      visual field during the procedure. Standard laparoscopic instrumentation is
      utilized for visualization and transanal excision of rectal pathologies.
      CONCLUSIONS: Transanal endoscopic video-assisted excision is an innovative
      approach to local excision of benign and malignant rectal lesions. The approach
      averts several of the pitfalls commonly experienced with transanal endoscopic
      microsurgery. Continued investigation and development of this novel modality will
      be important in establishing its role in minimally invasive surgery.

PMID- 21902944
TI  - Reduced-force closed trocar entry technique: analysis of trocar insertion force
      using a mechanical force gauge.
AB  - BACKGROUND AND OBJECTIVES: Trocar insertion injury has a high morbidity,
      mortality, and cost. The purpose of this study was to compare standard trocar
      entry with our reduced-force closed trocar entry technique by measuring trocar
      insertion force using a mechanical force gauge. METHODS: In the operating room,
      the force gauge was inserted into a sterile glove and connected to the proximal
      portion of the trocar to measure insertion force. Through one incision, we used a
      standard closed trocar entry, while through the other incision, we used our
      reduced-force closed trocar entry technique. After making the skin incision and
      before trocar entry, we spread and dilated the skin, subcutaneous tissue, fascia,
      and muscle with a hemostat. RESULTS: Twenty-five patients entered the trial and
      none were excluded. Median trocar insertion force was 3.3lb (range, 1.6 to 5.4)
      with our reduced-force trocar entry technique versus 6.5lb (range, 2.0 to 14.0)
      with the standard trocar entry (P=.001). No complications occurred with the
      reduced-force trocar entry technique. CONCLUSION: Our reduced-force trocar entry
      technique decreases trocar insertion force by 50%, requires no additional
      instruments or cost and is fast and safe. Reduced-entry force pressure may
      decrease the risk of trocar insertion injury.

PMID- 21902945
TI  - UREKA: umbilical ring easy kannula access.
AB  - BACKGROUND AND OBJECTIVES: Standard techniques of laparoscopic access involve
      creating an abdominal wall defect and can result in complications. We describe
      the umbilical ring easy kannula access (UREKA) technique, evaluating safety and a
      decrease in complications related to port placement. METHODS: UREKA is performed
      via a supra- or infraumbilical incision followed by circumferential dissection of
      the umbilical stalk. The umbilical skin is dissected free from the fascia,
      exposing the umbilical ring. Pneumoperitoneum is established either before or
      after placement of a dilating port through the open ring. We reviewed all
      laparoscopic procedures performed by one pediatric surgeon over 14 months using
      UREKA. RESULTS: Ninety-four patients underwent laparoscopic surgery with initial
      port placement via UREKA. Appendectomy (n=57) was the most common procedure,
      followed by fundoplication (15) and cholecystectomy (10). No intestinal, solid
      organ, vascular, or bladder injuries related to port placement occurred. The only
      postoperative complication was a superficial wound infection in a 135-kg patient
      following cholecystectomy, treated successfully with oral antibiotics alone.
      CONCLUSION: The umbilical ring persists to some degree in all pediatric patients
      and provides a safe portal of entry for laparoscopic surgery. UREKA has few
      complications and is a straightforward, reproducible technique for gaining
      initial laparoscopic access.

PMID- 21902946
TI  - Routine testing of liver function before and after elective laparoscopic
      cholecystectomy: is it necessary?
AB  - BACKGROUND AND OBJECTIVES: Liver function tests (LFTs) include alanine
      aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl
      transpeptidase (GGT), alkaline phosphatase (ALP), and bilirubin. The role of
      routine testing before and after laparoscopic cholecystectomy was evaluated in
      this study. PATIENTS AND METHODS: A total of 355 patients were retrospectively
      analyzed by examining the LFTs the day before, the day after, and 3 weeks after
      the surgery. The Wilcoxon signed-rank test and Student t test were performed to
      determine statistical significance. RESULTS: Alterations in the serum AST, ALT,
      and GGT were seen on the first postoperative day. Minor changes were seen in
      bilirubin and ALP. An overall disturbance in the LFTs was seen in more than two
      thirds of the cases. Repeat LFTs performed after 3 weeks on follow-up were found
      to be within normal limits. CONCLUSION: Mild-to-moderate elevation in
      preoperative LFTs may not be associated with any deleterious effect, and, in the
      absence of clinical indications, routine preoperative or postoperative liver
      function testing is unnecessary.

PMID- 21902947
TI  - Tissue reaction to absorbable endoloop, nonabsorbable titanium staples, and
      polymer Hem-o-lok clip after laparoscopic appendectomy.
AB  - BACKGROUND AND OBJECTIVES: The standard technique for securing the base of the
      appendix during laparoscopic appendectomy is by absorbable endoloop ligature,
      although clinical reports favor the use of the stapler. Nonabsorbable Hem-o-lok
      clips have been shown to be an alternative technique to this. However, it is
      currently not clear whether nonabsorbable clips have any effects on the intestine
      or promote infection in the surgical area. MATERIALS AND METHODS: Sixty Wistar
      albino rats were randomized into 3 treatment groups: group I (n=20) the base of
      the appendix was secured by endoloop 2-0 ligature; group II (n=20) dissection of
      the appendix was performed by a 45-mm thick stapler; and group III (n=20) the
      base of the appendix was secured by a Hem-o-lok plastic clip. The animals were
      sacrificed on the 14th and 28th days after surgery. The secured stump was used
      for histopathological examination. RESULTS: There were no significant differences
      in histopathological changes observed on the 14th postoperative day between the
      groups. On the 28th postoperative day, it was proved that mild and moderate
      inflammation is more frequent in the endoloop and Hem-o-lok groups than in the
      stapler group. Reaction to a foreign body is more frequent in the endoloop than
      in stapler and Hem-o-lok groups. CONCLUSION: The mildest postoperative
      inflammatory changes were seen in the stapler group, followed by the Hem-o-lok
      group. However, because of the price of the plastic clip and the simplicity of
      its application, its use is still favored during laparoscopic appendectomy.

PMID- 21902948
TI  - A simple, effective technique for port-site closure after laparoscopy.
AB  - BACKGROUND AND OBJECTIVES: Fascial closure of port sites represents a challenging
      issue in laparoscopic surgery. The aim of this article is to introduce a
      procedure that allows the safe suturing of the abdominal fascia in these wounds.
      METHODS: We herein describe a simple technique for fascial closure after
      laparoscopy using a transcutaneous approach and standard surgical instruments for
      suture. RESULTS: The method was used in 34 patients with no intraoperative
      incidents and no port-site hernias during a mean follow-up of 23.9 months (median
      20.5, range 5 to 47). CONCLUSION: The procedure is easy to perform, safe, fast,
      and inexpensive.

PMID- 21902949
TI  - Laparoscopic repair of incidentally found Spigelian hernia.
AB  - BACKGROUND AND OBJECTIVES: A Spigelian hernia is a rare type of hernia that
      occurs through a defect in the anterior abdominal wall adjacent to the linea
      semilunaris. Estimation of its incidence has been reported as 0.12% of all
      abdominal wall hernias. Traditionally, the method of repair has been an open
      approach. Herein, we discuss a series of laparoscopic repairs. METHODS: Case
      series and review of the literature. CASES: Three patients are presented. All
      were evaluated and taken to surgery initially for a different disease process,
      and all were incidentally found to have a spigelian hernia. These patients
      underwent laparoscopic repair of their hernias; 2 were repaired intraperitoneally
      and one was repaired totally extraperitoneally. Two patients initially underwent
      a mesh repair, while the third had an attempted primary repair. CONCLUSIONS:
      There is evidence that supports the use of laparoscopy for both diagnosis and
      repair of spigelian hernias. There are also reports of successful repairs both
      primarily and with mesh. In our experience with the preceding 3 patients, we
      found that laparoscopic repair of incidentally discovered spigelian hernias is a
      viable option, and we also found that implantation of mesh, when possible,
      resulted in satisfactory results and no recurrence.

PMID- 21902950
TI  - Robotic liver resection as a bridge to liver transplantation.
AB  - BACKGROUND: The surgical robotic system is superior to traditional laparoscopy in
      regards to 3-dimensional images and better instrumentation. Robotic surgery for
      hepatic resection has not yet been extensively reported. The aim of this article
      is to report the first known case of liver resection with the use of a robot in
      France. METHODS: A 61-year-old male with hepatitis C liver cirrhosis and
      hepatocellular carcinoma was referred for surgical treatment. Preoperative
      clinical evaluation and laboratory data disclosed a Child-Pugh class A5 patient.
      Magnetic resonance imaging showed a 3.4-cm tumor in segment III. Liver size was
      normal, and there were not signs of portal hypertension. Five trocars were used.
      RESULTS: Liver transection was achieved with Harmonic scalpel and bipolar forceps
      without pedicle clamping. Hemostasis of raw surface areas was accomplished with
      interrupted stitches. Operative time was 180 minutes. Blood loss was minimal, and
      the patient did not receive transfusion. The recovery was uneventful, and the
      patient was discharged on the fifth postoperative day without ascites formation.
      CONCLUSION: The robotic approach may enable liver resection in patients with
      cirrhosis. The da Vinci robotic system allowed for technical refinements of
      laparoscopic liver resection due to 3-dimensional visualization of the operative
      field and instruments with wrist-type end-effectors.

PMID- 21902951
TI  - Necrotizing fasciitis following endoscopic harvesting of the greater saphenous
      vein for coronary artery bypass graft.
AB  - The greater saphenous vein (GSV) remains the most commonly harvested conduit for
      revascularization in coronary artery bypass grafting (CABG). Published literature
      shows that minimally invasive vein harvesting techniques have a significantly
      lower incidence of wound infection rates than conventional open vein harvesting
      techniques have. We report a case of necrotizing fasciitis, an infection with a
      mortality rate of 30% to 50%, after endoscopic harvesting of the greater
      saphenous vein to be used as a conduit in a CABG procedure. Though minimally
      invasive vein harvesting techniques have advantages of smaller incisions and a
      decreased overall rate of wound infection, clinicians should be aware of this
      potentially lethal infection that may occur.

PMID- 21902952
TI  - Simultaneous bilateral single-port radical nephrectomies.
AB  - The management of bilateral enhancing renal masses can be technically
      challenging. Simultaneous bilateral laparoscopic nephrectomies in postrenal
      transplant patients have been previously described, but these typically require
      multiple port placements in addition to a hand port. Herein, we describe
      simultaneous bilateral single-port laparoscopic radical nephrectomies in a
      postrenal transplant patient.

PMID- 21902954
TI  - Acute cholecystits leading to ischemic ECG changes in a patient with no
      underlying cardiac disease.
AB  - Although chest pain with ST-segment elevation is often indicative of cardiac
      ischemia, it has also been described with surgical conditions such as acute
      cholecystitis. We report the case of a 34-year-old Caucasian female who was
      referred with symptoms consistent with acute cholecystitis. An electrocardiogram
      (ECG) showed unexpected changes with inferolateral ST-segment elevation
      indicative of an inferolateral myocardial infarct. Further investigations and
      analysis of the results along with the clinical picture meant an acute cardiac
      event was excluded. Gallstones were seen on ultrasound and an inflamed
      gallbladder, consistent with acute cholecystitis, was confirmed at laparoscopic
      cholecystectomy. This led to the resolution of her symptoms and a return to the
      isoelectric baseline of the ST segments on the ECG. Five previous cases of
      cholecystitis induced ECG changes have been described in the literature. This
      case describes the youngest patient with no previous cardiac disease. We review
      the literature and suggest the pathophysiological mechanism to explain these
      findings. When the initial diagnostic interventions for chest pain with ST
      segment elevation do not yield the expected results, an alternative diagnosis
      such as cholecystitis should be considered.

PMID- 21902953
TI  - Laparoscopic adrenalectomy for bilateral metachronous aldosteronomas.
AB  - INTRODUCTION: Primary aldosteronism affects 5% to 13% of patients with
      hypertension. Idiopathic bilateral hyperplasia (IHA) and unilateral aldosterone
      producing adenoma (APA) are the most common types of primary aldosteronism.
      Bilateral APA is a very rare entity with only a few reports in the literature. We
      present the case of a patient with metachronous bilateral APA treated with
      metachronous bilateral total and near total adrenalectomy. CASE REPORT: A 66-year
      old female was evaluated for hypokalemia and hypertension refractory to medical
      therapy 2 years after laparoscopic adrenalectomy for right APA. Follow-up
      abdominal CT scan revealed a new 1.1-cm left adrenal mass. The patient underwent
      a laparoscopic near total adrenalectomy for her new left adrenal mass. Pathology
      examination revealed a new APA. The operation and the patient's postoperative
      course were uneventful. Potassium levels were normalized and her hypertension
      became well controlled. CONCLUSION: APA can present metachronously months to
      years after adrenalectomy for APA in the contralateral adrenal gland.
      Laparoscopic adrenalectomy remains the approach of choice for this pathology.

PMID- 21902955
TI  - Using the StomaphyX(TM) endoplicator to treat a gastric bypass complication.
AB  - BACKGROUND AND OBJECTIVES: As the number of bariatric operations performed
      increases, the number of patients requiring reoperation for failed weight loss is
      expected to proportionately increase. Natural orifice surgery is an alternative
      approach to revisional gastric bypass surgery when postoperative complications,
      such as dilatation of the gastrojejunostomy, gastrogastric fistula, and gastric
      pouch, dilation occur. METHODS: The present article reports on the safe and
      successful use of an endoscopic tissue plicating device in a patient found to
      have a dilated gastric pouch and a gastrogastric fistula 12 years after an open,
      nondivided RYGB. RESULTS: The procedure was performed without complications and
      resulted in a reduced pouch size to approximately 30cc to 50cc and redirection of
      the flow of gastric contents through her gastrojejunostomy. The patient's early
      satiety returned and, 1 year postoperatively, she had incurred a 45-pound weight
      loss. DISCUSSION: The morbidity and mortality of revision gastric bypass was
      avoided while the patient's goal of moderate weight loss was achieved. Tissue
      plicating devices offer an alternative for repair of some postbariatric
      complications. With the rapid advances in endoluminal technology and increasing
      experience with natural orifice surgery, the ability to successfully address
      surgical problems through less invasive means will continue to improve.

PMID- 21902956
TI  - Large subcapsular liver hematoma following single-incision laparoscopic
      cholecystectomy.
AB  - BACKGROUND AND OBJECTIVES: Many laparoscopic surgeons are now transitioning from
      standard multiple-port laparoscopic cholecystectomy to single-incision
      laparoscopic surgery (SILS) in an attempt to improve cosmetic outcomes and
      decrease postoperative morbidity. However, little has been published regarding
      the potential complications of SILS operations. METHODS: We report the case of a
      patient undergoing SILS cholecystectomy who developed the complication of a large
      hepatic hematoma, resulting in significant postoperative morbidity, blood
      transfusion requirement, and reoperation. RESULTS: After an in-depth internal
      review of the postoperative morbidity of this case, it appears that the causative
      factor may be instrument shaft torque on the liver surface. CONCLUSION: Single
      incision laparoscopic surgery may pose significant and unique risks that warrant
      additional operative caution. Quantitative comparison of SILS to the gold
      standard laparoscopic cholecystectomy is needed to further elucidate definitive
      benefits and complications of this novel technique.

PMID- 21902957
TI  - Retraction-related liver lobe necrosis after laparoscopic gastric surgery.
AB  - BACKGROUND: Liver retraction is necessary for optimal exposure during
      laparoscopic gastric surgery. Though transient venous congestion of the retracted
      lobe of the liver is invariably seen during operations, major parenchymal injury
      is rare. We describe a case of Nathanson liver retractor-induced left lobe liver
      necrosis and review the pertinent literature. CASE REPORT: A 78-year-old man
      underwent a laparoscopic-assisted total gastrectomy for gastric cancer. A
      Nathanson liver retractor was used to retract a large fatty left liver lobe. The
      operation was prolonged due to splenic bleeding requiring splenectomy. On the
      second postoperative day, the patient deteriorated rapidly and developed multi
      organ failure. A computerized tomogram confirmed necrosis of the left lobe of the
      liver with gas in the liver parenchyma. The necrotic liver lobe was excised at
      reoperation. The patient died from a postoperative myocardial infarction.
      DISCUSSION: Though minor liver injuries, in the form of intraoperative trauma and
      congestion, are common with laparoscopic liver retraction, major lacerations and
      necrosis are rare. Prolonged surgery and enlarged fatty liver lobe increases the
      risks of major injury. In our report, we discuss various types of retractor
      related liver injuries and their management and highlight the importance of
      intermittent release of retraction during prolonged surgery.

PMID- 21902958
TI  - Laparoscopic 5-mm trocar site herniation and literature review.
AB  - OBJECTIVE: To evaluate the evidence for fascial closure of 5-mm laparoscopic
      trocar sites. METHODS: We conducted electronic database searches of PubMed and
      the Cochrane Library for articles published between November 2008 and December
      2010. We used the keywords trocar hernia, trocar-site hernia, laparoscopic
      hernia, trocar port-site hernia, laparoscopic port-site hernia. Prospective and
      retrospective case series, randomized trials, literature reviews, and randomized
      animal studies of trocar hernias on abdominal wall defects from gynecologic,
      urologic, and general surgery literature were reviewed. The Cochrane Database was
      reviewed for pertinent studies. Metaanalysis was not possible due to the
      significant heterogeneity between studies and lack of randomized trials large
      enough to assess the incidence of this rare complication. RESULTS: Trocar-site
      hernias are a rare but known complication of laparoscopic surgery. Trocar size
      >=10mm is associated with an increased rate of hernia development. Currently, the
      accepted gynecologic surgical practice is closure of fascial incisions >=10mm,
      while incisions <10mm do not require closure. However, large prospective and
      retrospective case series reports from general surgery and urology literature
      support nonclosure of blunt or radially dilating trocars in paramedian sites.
      Expert opinion and small case reports suggest that in cases of prolonged
      manipulation of 5-mm trocar sites the surgeon should consider fascial closure,
      because extension of the initial incision may have occurred. CONCLUSION: There is
      no evidence to recommend routine closure of 5-mm trocar incisions; the choice
      should continue to be left to the discretion of the individual surgeon.

PMID- 21902959
TI  - The wandering Mirena: laparoscopic retrieval.
AB  - Levonorgestrel-containing intrauterine contraceptive devices, marketed as Mirena
      (Bayer HealthCare Pharmaceuticals, Inc. Australia) are widely used in
      contemporary gynecology, primarily as an effective method for contraception and
      for control of menstrual disorders like menorrhagia and dysmenorrhea. In this
      article, the authors report 2 cases of Mirena migration following intrauterine
      insertion by general practitioners (family physicians). In the first case, the
      contraceptive device had moved to the patient's right iliac fossa just anterior
      to the cecum and, in the second, within the peritoneal cavity close to the left
      leaf of the diaphragm. Both patients underwent uneventful laparoscopic retrieval
      of the devices.

PMID- 21902960
TI  - "Do no harm"--ORReady initiative aims to improve safety and outcome for 6 million
      patients.

PMID- 21902961
TI  - Laparoscopy and natural orifice surgery: first entry safety surveillance step.
AB  - BACKGROUND AND OBJECTIVE: We are sharing information regarding the surveillance
      of the first entrance port in laparoscopic and natural orifice transvaginal
      endoscopy surgeries. However, we are not analyzing techniques or other surgical
      findings. METHOD: In this study, 160 women with previous abdominal pelvic
      surgeries underwent laparoscopic surgery, 145 patients underwent transvaginal
      Minilaparoscopy Assisted Natural Orifice Surgery (hybrid), and 3 patients
      underwent pure natural orifice transvaginal endoscopic surgery (pure). For those
      patients who had laparoscopy and hybrid procedures, the surveillance was from a
      laparoscope or gastroscope placed in a secondary port. Surveillance in pure cases
      was done using a gastroscopic retro view to see the pouch of Douglas. RESULTS:
      The laparoscopic procedures were gynecological procedures. The hybrid procedures
      included gynecological procedures as well as appendectomies and
      cholecystectomies; the pure procedures were cholecystectomies. There were a few
      minor vascular and bowel injuries in the laparoscopy group. There were no
      injuries in the transvaginal hybrid or pure procedures groups. CONCLUSION: The
      surveillance of the first entrance port can be an effective precautionary step.
      The cumulative experience suggests that using such surveillance in cases
      involving patients with prior surgery may assist in recognizing complications
      that might otherwise be missed.

PMID- 21902962
TI  - Single-port surgery: laboratory experience with the daVinci single-site platform.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the
      feasibility and validity of a dedicated da Vinci single-port platform in the
      porcine model in the performance of gynecologic surgery. METHODS: This pilot
      study was conducted in 4 female pigs. All pigs had a general anesthetic and were
      placed in the supine and flank position. A 2-cm umbilical incision was made,
      through which a robotic single-port device was placed and pneumoperitoneum
      obtained. A data set was collected for each procedure and included port placement
      time, docking time, operative time, blood loss, and complications. Operative
      times were compared between cases and procedures by use of the Student t test.
      RESULTS: A total of 28 surgical procedures (8 oophorectomies, 4 hysterectomies, 8
      pelvic lymph node dissections, 4 aorto-caval nodal dissections, 2 bladder
      repairs, 1 uterine horn anastomosis, and 1 radical cystectomy) were performed.
      There was no statistically significant difference in operating times for
      symmetrical procedures among animals (P=0.3215). CONCLUSIONS: This animal study
      demonstrates that singleport robotic surgery using a dedicated single-site
      platform allows performing technically challenging procedures within acceptable
      operative times and without complications or insertion of additional trocars.

PMID- 21902963
TI  - Virtual reality uterine resectoscopic simulator: face and construct validation
      and comparative evaluation in an educational environment.
AB  - BACKGROUND AND OBJECTIVES: Recognizing that resectoscopic simulation may have an
      educational role, this pilot study was designed to evaluate the face validity and
      educational utility of a virtual reality uterine resectoscope training system.
      METHODS: A pilot prospective comparative study of novice and expert
      hysteroscopists' performance on a targeting exercise and myomectomy with the
      virtual loop electrode. At baseline, expert and novice resectoscopists each
      performed both exercises. Following instruction, novices practiced each exercise
      a total of 9 times with the 10th recorded as the training outcome. Results were
      compared both to baseline and to those of the experts. Data were analyzed with
      the paired t and Wilcoxon rank sum tests as appropriate. RESULTS: At baseline,
      all experts touched 4 targets in a mean of 33 seconds with no perforations,
      compared to a mean of 2 for the 11 novices in a mean of 57 seconds (P=0.0034)
      with one perforation. In 3 minutes, the experts removed a mean of 97.3% of the
      virtual myoma, compared to 66.1% for the novices (P=0.0153). On the 10th "run,"
      novices touched a mean of 4 targets in a mean of 23 seconds, an improvement from
      baseline (P=0.0004) and improved to 89% on the myoma resection exercise
      (P=0.0515) 36.3% over baseline. CONCLUSION: Although this pilot study has a
      relatively small sample size and represents the results at one institution, it
      demonstrates that virtual reality resectoscopic systems have the potential to
      measure and improve the technical skills of novices before they operate on human
      patients.

PMID- 21902965
TI  - Defining "laparoscopy" through review of technical details in JSLS.
AB  - BACKGROUND AND OBJECTIVES: The term "laparoscopy" has lost some precision in its
      definition due to the proliferation in techniques of access to the abdominal
      cavity. Currently, procedures performed with radical differences in port size,
      placement, and even need for an extraction incision may be characterized as
      "laparoscopic." However, the general public and many insurers divide procedures
      in the simplified categories of laparoscopic or open. Our aim was to characterize
      the typical laparoscopic operation through review of the technical details of a
      year's worth of articles in JSLS. METHODS: We assembled and analyzed a database
      of all articles in JSLS from 2008-2009 (4 issues starting with Volume 12, #4).
      For comparison, we also reviewed articles from 1 decade ago (Volume 2). All
      procedural details were compiled, including means of access, number and size of
      ports, incision length, and conversion rates. RESULTS: In the most recent year,
      there were 81 articles for analysis, compared to 39 in the earlier year. Few
      articles listed all technical details, as only 58% of reports described mode of
      access and 56% described the number of ports used. Access was nearly evenly
      divided between Hasson and Veress techniques. The average number of ports in both
      study periods was 4, although there was a trend toward smaller port sizes in the
      current year. Among those studies specifying incision length, the average was
      6.1cm in both groups. CONCLUSION: The technical operative details are lacking in
      many reports. Based on review of published studies, most procedures are done with
      4 ports, 3 of which are >=10mm in size. Until there is greater clarity in
      technical description, the precise definition of laparoscopy will remain elusive.

PMID- 21902964
TI  - A simple vacuum dressing reduces the wound infection rate of single-incision
      pediatric endosurgical appendectomy.
AB  - BACKGROUND AND OBJECTIVES: After introducing single-incision pediatric
      endosurgical (SIPES) appendectomy at our institution, we noticed an increased
      number of post-operative umbilical infections. This study evaluates the impact of
      a simple, low-cost wound vacuum dressing on the wound infection rate. METHODS:
      Umbilical wounds after single-incision laparoscopic appendectomy were covered
      with standard dressing (approximating strips), or the new umbilical vacuum
      dressing. A wound infection was defined as an infected umbilicus requiring
      antibiotics, or incision and drainage. The wound infection rate was compared
      between both groups. Statistical analysis was performed using Fischer's exact
      test. Continuous variables were compared using the Student t test. RESULTS:
      Included in this study were 183 children, 97 of whom were treated with the vacuum
      dressing. The study populations were no different in terms of age, weight,
      operative time, blood loss, length of stay, or proportion of acute versus
      perforated appendicitis. A total of 7 (3.8%) wound infections occurred, 1 in the
      vacuum dressing group (1%), versus 6 in the conventional dressing group (7%,
      P=0.038). CONCLUSIONS: This simple, low-cost umbilical vacuum dressing decreased
      the wound infection rate after SIPES appendectomy, possibly by absorbing
      secretions from the base of the wound. It may be equally effective for other
      indications.

PMID- 21902966
TI  - Sutureless laparoscopic ventral hernia repair in obese patients.
AB  - BACKGROUND AND OBJECTIVE: Transfascial sutures (TFS) are a standard component of
      laparoscopic ventral herniorrhaphy (LVHR) that contribute to the durability of
      repair, but also pain and, resultantly, hospital stay. We sought to examine LVHR
      without TFS in obese patients with small abdominal wall hernias. METHODS: Between
      September 2002 and December 2007, 174 patients underwent LVHR at Yale-New Haven
      Hospital. Patients with BMI >30kg/m(2) and small primary abdominal wall hernias
      were eligible for repair without TFS. Correlation between BMI, defect surface
      area, operative time, and postoperative stay was assessed. RESULTS: Fourteen
      patients underwent LVHR with no TFS, 2 with normal BMI and recurrent hernia after
      open repair and 12 with BMI >30 kg/m(2) and primary small hernia. Mean age was
      38.8 years. The average defect size was 5.3cm(2); mean operative time (OT) was 42
      minutes. Eleven patients (92%) were discharged home the day of surgery. No
      infectious or bleeding complications occurred. One patient required chronic pain
      management, and 8 patients (67%) developed seromas that resorbed spontaneously.
      There was no hernia recurrence at 7-month follow-up. CONCLUSION: LVHR is feasible
      without TFS provided the hernia defect is small. Surgery can be performed on an
      outpatient basis in obese individuals with minimal postoperative morbidity.

PMID- 21902967
TI  - NiTiNol hernia device stability in inguinal hernioplasty without fixation.
AB  - BACKGROUND AND OBJECTIVE: To determine whether the NiTiNol frame of a novel
      hernia repair device utilizing polypropylene mesh for inguinal hernioplasty
      remains stable and intransient without fixation after a minimum of 6 months.
      METHODS: Twenty patients had 27 inguinal hernias repaired using a novel hernia
      repair device that has a NiTiNol frame without any fixation. Initial single-view,
      postoperative X-rays were compared with a second X-ray obtained at least 6 months
      later. The NiTiNol frame, which can be easily visualized on a plain X-ray, was
      measured in 2 dimensions, as were anatomic landmarks. The measurements obtained
      and the appearances of the 2 X-rays were compared to determine the percentage of
      change in device size and device stability with regard to device location and
      shape. RESULTS: There were minimal changes noted between the 2 sets of
      measurements obtained with an overall trend towards a slight increase in the size
      of the hernia repair device. The devices demonstrated intransience of position
      and stability of shape. CONCLUSIONS: The NiTiNol frame of a novel hernia repair
      device utilizing polypropylene mesh exhibits radiographic evidence of size and
      shape stability and intransience of position without fixation when used in
      inguinal hernioplasty after a minimum follow-up of 6 months.

PMID- 21902968
TI  - Single incision laparoscopic ventral hernia repair.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic ventral hernia repair (LVH) requires
      several skin incisions for trocar placement. We have developed a single incision
      approach to LVH repair. The technique was introduced in clinical practice to any
      consenting patients who were candidates for a standard multi-port laparoscopic
      hernia repair. A consecutive series of patients was then followed to evaluate
      feasibility. METHODS: Over an 8-month period, 14 patients (9 females, 5 males)
      underwent LVH repair by an academic surgeon. One of 2 access methods was used in
      each patient through a single 1.5-cm to 2-cm skin incision. One technique
      utilized two 5-mm ports with a temporarily placed 11-mm port for mesh insertion.
      The second technique utilized the SILS port (Covidien, Norwalk, CT). Standard or
      roticulating laparoscopic instruments were used with both techniques. RESULTS:
      Range (mean) BMI: 23 to 59 (38), Age: 26 to 73 years (53), DURATION: 37 to 87
      minutes (57), Defect size: 1cm to 8cm (2), 3 with Swiss-cheese defect hernias.
      The procedure was successfully performed in all patients. No conversions to a
      multiple-port approach or to an open procedure were necessary. There were no
      mortalities, major complications, or recurrences during the mean follow-up period
      of 4 weeks. CONCLUSION: Single incision ventral hernia repair is technically
      feasible, effective, and reproducible. The technique is easy to master, and safe
      for any patient who is a candidate for laparoscopic ventral hernia repair.
      Further data collection with long-term follow-up will be needed to ensure
      equivalent outcomes. There will be demand for this approach by patients for
      cosmetic reasons, and it may serve as a bridge to natural orifice techniques.

PMID- 21902969
TI  - Laparoscopic gastrojejunostomy for the treatment of gastric outlet obstruction.
AB  - BACKGROUND AND OBJECTIVES: Laparoscopic gastrojejunostomy (LGJ) has been proposed
      as the technique preferred over open gastrojejunostomy for relieving gastric
      outlet obstruction (GOO) due to malignant and benign disease. This study
      investigates the feasibility and safety of LGJ for GOO. METHODS: A retrospective
      review was performed of patients who underwent LGJ at Mount Sinai Medical Center
      from 2004 to 2008. Patient's operative course and longterm outcomes were
      collected. RESULTS: Twenty-eight patients were reviewed (16 had malignancy, 7 had
      PUD, 3 had Crohn's disease, and one had obstruction of unclear cause). Average
      operative time was 170 minutes, and estimated blood loss was 80cc. One case was
      converted to open; another had stapler misfiring. Patients regained bowel
      function at a median of 3 days and remained in the hospital for a median of 8
      days. There were 4 major postoperative complications (14%): 1 anastomotic leak
      and 1 trocar-site hemorrhage requiring reoperation and 2 gastrointestinal bleeds
      requiring endoscopic intervention. There were 5 minor complications (18%),
      including a partial small bowel obstruction, 1 patient developed bacteremia, and
      3 patients had delayed gastric emptying. One patient had persistent GOO requiring
      reoperation 3 months later. CONCLUSION: LGJ can be performed for GOO with
      improved outcome and an acceptable complication rate compared to the open GJ
      reported in the literature.

PMID- 21902970
TI  - Contributing factors to postoperative length of stay in laparoscopic
      cholecystectomy.
AB  - BACKGROUND: Laparoscopic cholecystectomy for gallbladder disease is a common
      surgical procedure performed in hospitals throughout the world. This study
      evaluates the major factors that contribute to postoperative length of stay for
      patients undergoing laparoscopic cholecystectomy. METHODS: We analyzed data for
      patients undergoing laparoscopic cholecystectomy in a 5-hospital community health
      system from December 1, 2008 to January 31, 2009. The natural logarithm of
      postoperative length of stay was modeled to evaluate significant factors and
      contributions. RESULTS: Included in the analysis were 232 patients. Three
      preoperative patient factors were significant contributors: body mass index was
      associated with decreased postoperative length of stay, while white blood cell
      count and the presence of biliary pancreatitis were associated with increased
      postoperative length of stay. The operative factors of fluids administered and
      ASA class were significant contributors to increased postoperative length of
      stay, with an increasing contribution with a higher ASA class. The utilization
      factor of nonelective status was a significant contributor to increased
      postoperative length of stay. CONCLUSION: Several factors were major contributors
      to postoperative length of stay, with ASA class and nonelective status having the
      most significant increased contribution. Efforts to optimize efficient elective
      care delivery for patients with symptomatic gallbladder disease may demonstrate a
      benefit of decreased hospital utilization.

PMID- 21902971
TI  - Use of laparoscopy in trauma at a level II trauma center.
AB  - BACKGROUND AND OBJECTIVES: Enthusiasm for the use of laparoscopy in trauma has
      not rivaled that for general surgery. The purpose of this study was to evaluate
      our experience with laparoscopy at a level II trauma center. METHODS: A
      retrospective review of all trauma patients undergoing diagnostic or therapeutic
      laparoscopy was performed from January 2004 to July 2010. RESULTS: Laparoscopy
      was performed in 16 patients during the study period. The average age was 35
      years. Injuries included left diaphragm in 4 patients, mesenteric injury in 2,
      and vaginal laceration, liver laceration, small bowel injury, renal laceration,
      urethral/pelvic, and colon injury in 1 patient each. Diagnostic laparoscopy was
      performed in 11 patients (69%) with 3 patients requiring conversion to an open
      procedure. Successful therapeutic laparoscopy was performed in 5 patients for
      repair of isolated diaphragm injuries (2), a small bowel injury, a colon injury,
      and placement of a suprapubic bladder catheter. Average length of stay was 5.6
      days (range, 0 to 23), and 75% of patients were discharged home. Morbidity rate
      was 13% with no mortalities or missed injuries. CONCLUSIONS: Laparoscopy is a
      seldom-used modality at our trauma center; however, it may play a role in a
      select subset of patients.

PMID- 21902972
TI  - Impact of conversion on short and long-term outcome in laparoscopic resection of
      curable colorectal cancer.
AB  - INTRODUCTION: Long-term outcome of patients following conversion during
      laparoscopic surgery for colorectal cancer is not often reported. Recent data
      suggest a negative impact of conversion on long-term survival. This study aimed
      to evaluate the impact of conversion on the perioperative outcome and on long
      term survival in patients who underwent laparoscopic resection for curable
      colorectal cancer. METHODS: Evaluation of our prospective in-hospital collected
      data of patients who underwent laparoscopic surgery for curable colorectal cancer
      over a 5-year period. Long-term data were collected from our outpatient's clinic
      data and personal contact when necessary. RESULTS: During the study period, 175
      patients were operated on laparoscopically for curable colon cancer (stage I
      III). Mean follow-up was 33+/-18 months with a minimum follow-up of 12 months.
      For various reasons, 25 patients (14.4%) had to be converted to open surgery.
      Short-term outcome revealed a trend towards longer operations, a higher rate of
      surgical complications, and a longer hospital stay in the converted group. Five
      year, Kaplan-Meier, disease-free analysis was worse for converted patients.
      Overall survival did not differ between the 2 groups. Cox proportional hazards
      regression analysis revealed that conversion and AJCC stage were independent risk
      factors for recurrence. CONCLUSIONS: Conversion in laparoscopic surgery for
      curable colorectal cancer is associated with a worse perioperative outcome and
      worse disease-free survival.

PMID- 21902973
TI  - Combined treatment of symptomatic massive paraesophageal hernia in the morbidly
      obese.
AB  - INTRODUCTION: Repair of large paraesophageal hernias by itself is associated with
      high failure rates in the morbidly obese. A surgical approach addressing both
      giant paraesophageal hernia and morbid obesity has, to our knowledge, not been
      explored in the surgical literature. METHODS: A retrospective review of a
      bariatric surgery database identified patients who underwent simultaneous repair
      of large type 3 paraesophageal hernias with primary crus closure and Roux-en-Y
      gastric bypass (RYGB). Operative time, intraoperative and 30-day morbidity,
      weight loss, resolution of comorbid conditions and use of antireflux medication
      were outcome measures. Integrity of crural closure was studied with a barium
      swallow. RESULTS: Three patients with a mean body mass index of 46kg/m(2) and
      mean age of 46 years underwent repair of a large paraesophageal hernia, primary
      crus closure, and RYGB. Mean operative time was 241 minutes and length of stay
      was 4 days. There was no intraoperative or 30-day morbidity. One patient required
      endoscopic balloon dilatation of the gastrojejunostomy. At 12 months, all
      patients were asymptomatic with excellent weight loss and resolution of
      comorbidities. Contrast studies showed no recurrence of the hiatal hernia.
      CONCLUSION: Simultaneous laparoscopic repair of large paraesophageal hernias in
      the morbidly obese is safe and effective.

PMID- 21902974
TI  - Robotic radical prostatectomy at a teaching community hospital: outcomes and
      safety.
AB  - OBJECTIVES: This study describes the early experience of robotic prostatectomy
      exclusively at a teaching community hospital. METHODS: This is a retrospective
      report of 153 consecutive patients on whom 4 physicians were the operating
      surgeon. RESULTS: The average hospital stay was 1.5 days, the mean operative time
      was 175 minutes, and the estimated operative blood loss was <300mL. The
      perioperative complication rate was 7.8% (12/153). The prostate-specific antigen
      failure rate was 2% (2/114). Urinary continence was maintained in 98% of patients
      9 months after surgery. Postoperative Gleason scores differed significantly from
      preoperative biopsy results (P<0.001). Pathological records reported positive
      margins in 35% (54/153) of specimens. T3 tumors had positive margins more than
      twice as often as T2 tumors (P<0.002). Surgeon experience correlated with shorter
      operative times (P=0.001), but not with positive margins. Increasing body mass
      index was associated with increased operating time (P<0.001). CONCLUSIONS:
      Robotic prostatectomy appears to be a safe and successful option for prostate
      cancer treatment in a teaching community hospital.

PMID- 21902975
TI  - Side docking the robot for robotic laparoscopic radical prostatectomy.
AB  - BACKGROUND AND OBJECTIVES: Low lithotomy position with the robot between the legs
      for docking is a standard position for robotic radical prostatectomy. Its
      complications include occasional nerve injury and compartment syndrome. In some
      patients with conditions that limit hip abduction, this position may be
      infeasible. We report a docking technique that obviates stirrups and simplifies
      setup without altering surgical technique. METHODS: A total of 100 consecutive
      patients underwent robotic radical prostatectomy for localized prostate cancer.
      Fifty patients (group 1) were in the standard lithotomy position, and the
      remaining 50 patients (group 2) were in slight trendelenburg position with the
      robot at the side of the bed - "side-docked." Setup and docking times were
      recorded and both groups were compared for differences in operative variables.
      RESULTS: Mean setup time for group 2 was 4.7 minutes shorter than for group 1 (p
      = 0.02). Docking time and other operative variables were statistically similar
      and not affected by the adoption of side-docking technique. However, overall
      surgical time was longer due to modifications in other aspects of the technique
      during the study period. CONCLUSION: Side-docking for robotic radical
      prostatectomy is associated with small but significant improvement in setup time
      and can be utilized in patients with limited hip abduction.

PMID- 21902976
TI  - Hand-assisted laparoscopy confers equal efficacy in simple and radical
      nephrectomy.
AB  - BACKGROUND AND OBJECTIVES: To evaluate outcomes for simple hand-assisted
      laparoscopic nephrectomy (HALSN). METHODS: A retrospective chart review was
      performed at our institution for all patients who had undergone HALSN from
      January 2002 to January 2009. Thirty-three patients underwent HALSN during this
      time period and were matched with 33 patients who underwent radical handassisted
      laparoscopic nephrectomy (HALRN). RESULTS: Operative times were similar between
      both groups (301 vs 286 min for HALSN vs HALRN; P=.54). There were no
      intraoperative or postoperative transfusions in either group. There was one
      conversion to open nephrectomy in the HALSN group in a patient with
      xanthogranulomatous pyelonephritis and no conversions in the HALRN group. The
      mean opioid equivalence requirement was not statistically different between both
      groups (110 vs 120 for HALSN vs HALRN, P=.70). Mean hospital stay was similar for
      patients undergoing HALSN and HALRN (5.0+/-3.8 days vs 4.0+/-1.2 days, P=.63).
      There was 1 major complication in the HALSN group (pulmonary embolus) and no
      major complications in the HALRN group. Rates of minor complications were
      comparable between the 2 groups (18% vs 24% for HALSN vs HALRN). CONCLUSIONS:
      HALSN may be associated with similar operative times and length of postoperative
      hospital stay as well as comparable complication rates compared to HALRN.

PMID- 21902977
TI  - Evolution of minimally invasive surgery for donor nephrectomy and outcomes.
AB  - BACKGROUND: Laparoscopic donor nephrectomy was introduced into Australia in 1997
      by this unit. However, some donors may be considered unsuitable, and few
      modifications to the existing technique can tailor this procedure for an
      individual donor. Recently, further changes including clustering of ports and
      single-port methods have been investigated. METHODS: The laparoscopic method was
      offered to all but 3 donors from May 1997 to October 2009. Data were collected on
      all 289 donors who underwent laparoscopic procedures. RESULTS: All but 5 donor
      procedures were completed laparoscopically, and in 4 of them conversion to open
      was necessary due to hemorrhage. The fifth was a planned conversion in our first
      right LDN. Delayed graft function was seen in 7 recipients and 5 required
      dialysis postoperatively. Two kidneys were lost due to arterial thrombosis, and 5
      patients underwent segmental infarction with decreased renal function. Mean
      hospital stay was 2.35+/-1.67 days. There were no donor deaths or serious
      morbidity. CONCLUSIONS: Although the benefits to the donor of the laparoscopic
      method are well recognized, our modifications will benefit those who may be
      precluded from this method.

PMID- 21902978
TI  - Radical hysterectomy for early stage cervical cancer: laparoscopy versus
      laparotomy.
AB  - OBJECTIVES: Gynecologic oncologists have recently begun using laparoscopic
      techniques to treat early stage cervical cancer. We evaluated a single
      institution's experience of laparoscopic radical hysterectomy and staging
      compared with laparotomy. METHODS: A retrospective chart review identified stage
      IA2 and IB1 cervical cancer patients who underwent laparoscopic radical
      hysterectomy and pelvic lymph node dissection from July 2003 to April 2009. A 2:1
      cohort of patients treated with laparotomy were matched by stage. RESULTS: Nine
      laparoscopic patients (3 stage IA2, 6 stage IB1) with 18 matched controls (6 and
      12) were identified. Demographics for each group were similar. None had positive
      margins or lymph nodes. An average of 11.2 vs.13.9 pelvic lymph nodes (P=0.237)
      were removed. Average operating time was 231.7 vs. 207.2 minutes (P=0.434), and
      average estimated blood loss was 161.1 vs. 394.4mL (P=0.059). Average length of
      stay was 2.9 vs. 5.5 days (P=0.012). No transfusions or operative complications
      were noted in the laparoscopic group vs. 3 each in the open group (P=0.194). No
      laparoscopic patients and 5 open patients had a postoperative wound infection
      (P=0.079). No recurrences were noted. CONCLUSIONS: Laparoscopic radical
      hysterectomy is a feasible alternative to laparotomy for early stage cervical
      cancer. Similar surgical outcomes are achieved with significantly less morbidity.

PMID- 21902979
TI  - Total laparoscopic hysterectomy and laparoscopy-assisted vaginal hysterectomy.
AB  - BACKGROUND AND OBJECTIVES: To compare the feasibility of total laparoscopic
      hysterectomy (TLH) and laparoscopy-assisted vaginal hysterectomy (LAVH) in the
      treatment of benign gynecologic diseases and to determine the selection criteria
      for each technique. METHODS: This was a retrospective medical records review of
      168 patients who underwent TLH or LAVH performed by one surgeon. A chi-square
      test was used to compare the difference between the TLH and LAVH groups.
      Pearson's correlation coefficient was calculated for the relationship between the
      clinico-demographic factors of the patients. RESULTS: There were no differences
      between the 2 groups with respect to age, parity, history of abdominal delivery,
      body mass index, and indication for hysterectomy. The operative time was similar
      between the 2 groups (P>.99). The uterine weight was greater in the LAVH group
      compared to the TLH group (P<.01). Ten patients were converted from TLH to LAVH,
      because of a large uterus and/or a lower segmental mass on the uterus, making it
      difficult to expose the Koh cup rim contour. CONCLUSIONS: TLH and LAVH are safe,
      feasible methods by which to perform a hysterectomy. LAVH is preferred in
      patients with a mass involving the lower segment or a relatively large uterus.

PMID- 21902980
TI  - Single-port transumbilical laparoscopic-assisted adnexal surgery.
AB  - OBJECTIVES: To evaluate the efficiency and feasibility of single-port access
      transumbilical laparoscopic-assisted surgery in patients with large (>8cm)
      adnexal tumors and to present our initial experience. METHODS: Twenty-two
      patients with presumably benign adnexal tumors who have undergone single-port
      access transumbilical laparoscopic-assisted surgery were enrolled. The procedure
      was performed using the method of exteriorization and extracorporeal surgery of
      adnexal tumors outside the abdominal cavity under laparoscopic guidance with
      preservation of as much ovarian tissue as possible. In each case, a homemade
      single-port device was inserted into the abdomen through a 2-cm umbilical
      incision. The clinical characteristics and operative outcomes of these patients
      were reviewed. RESULTS: Twenty of 22 cases were completed successfully. The one
      failed case required an additional trocar for adequate adhesiolysis, and the
      other case needed intraperitoneal drainage. The median operating time was 50
      minutes (range, 35 to 120), and the estimated blood loss was 38mL (range, 10 to
      300). Cyst rupture occurred in 2 cases, but there were no major postoperative
      complications. CONCLUSION: Single-port access transumbilical laparoscopic
      assisted surgery for benign and relatively large adnexal tumors is feasible and
      could be an alternative to convention open laparotomy or laparoscopic surgery.

PMID- 21902981
TI  - Combined endoscopic and laparoscopic approach to a gastroesophageal tumor.
AB  - BACKGROUND AND OBJECTIVES: Smooth muscle tumors of the stomach, especially when
      benign, are a common clinical entity and can represent a therapeutic challenge.
      Classically the removal of such a tumor requires open laparotomy. We sought to
      perform this surgery utilizing minimally invasive technology. METHODS: We
      describe a minimally invasive technique combining laparoscopy with endoscopy to
      remove a sub-mucosal leiomyoma at the gastroesophageal junction. RESULTS: A 3.3
      cm smooth muscle tumor of the gastroesophageal junction was removed completely
      and safely with the described procedure and thus saved the patient from requiring
      a laparotomy. CONCLUSION: Minimally invasive techniques can be used in
      combination to tackle difficult problems in general surgery leading to shorter
      hospital stays and improved patient satisfaction.

PMID- 21902982
TI  - Surgical relief of small bowel obstruction by migrated biliary stent: extraction
      without enterotomy.
AB  - BACKGROUND: Distal stent migration is a well-known complication following
      insertion of biliary stents. Most such cases can be managed expectantly, because
      the stents pass through the gastrointestinal tract. However, small bowel
      obstruction as a result of the stent mandates surgical intervention. METHODS: We
      report the case of a patient who had distal stent migration causing a small bowel
      obstruction. We successfully retrieved the stent without an enterotomy, by using
      a combination of laparoscopy, endoscopy, and fluoroscopy. Our unique technique
      greatly decreased the risk of bacterial peritonitis in this patient with
      decompensated cirrhosis and associated ascites, which in this patient population
      results in a high mortality. RESULTS: Management of small bowel obstruction
      secondary to biliary stent migration necessitates operative intervention.
      Retrieval of a dislodged stent can be performed safely without subjecting the
      patient to an enterotomy or a small bowel resection. Postoperative morbidity
      should be significantly reduced by this approach. CONCLUSION: Retrieval of
      biliary stents in cases of small bowel obstruction without perforation may be
      successfully performed without enterotomy or bowel resection. A similar approach
      may be applied to other foreign bodies dislodged in the small bowel.

PMID- 21902983
TI  - Laparoscopic single site adrenalectomy using a conventional laparoscope and
      instrumentation.
AB  - BACKGROUND AND OBJECTIVES: We present a case of Laparoendoscopic Single Site
      Surgery (LESS) left adrenalectomy performed with a conventional laparoscope and
      instruments. METHODS: A 45-year-old male was diagnosed with hyperaldosteronism.
      Computed tomography detected a left adrenal nodule. Bilateral adrenal vein
      sampling was consistent with a left-sided source for hyperaldosteronism. RESULTS:
      Total operative time for LESS left adrenalectomy was 120 minutes. The surgery was
      performed with conventional instruments, a standard 5-mm laparoscope, and a SILS
      port, with no additional incisions or trocars needed. No complications occurred,
      and the patient reported an uneventful recovery. CONCLUSIONS: LESS adrenalectomy
      is a feasible procedure. Although articulating instruments and laparoscopes may
      offer advantages, LESS adrenalectomy can be done without these.

PMID- 21902984
TI  - Single-incision laparoscopic cholecystectomy in situs inversus totalis.
AB  - BACKGROUND AND OBJECTIVES: Situs inversus totalis (SIT) is a rare congenital
      anomaly that can cause difficulties during standard laparoscopic cholecystectomy
      due to its mirror-image anatomy. These cases require more technically demanding
      procedures, and handedness of the surgeon may influence performance of these
      operations. Single-incision laparoscopic surgery (SILS) has been proposed as a
      less-invasive alternative to conventional laparoscopic surgery. We report the
      first case of successful SILS cholecystectomy in a patient with SIT and discuss
      technical aspects of the operation related to the handedness of the surgeon.
      CASE: A 49-year-old man who was known to have situs inversus totalis presented
      with symptomatic cholelithiasis. This patient was operated on by a right-handed
      surgeon. The surgeon and camera assistant were positioned on the right and left
      side respectively with the video monitor above the patient's left shoulder. The
      SILS port (Covidien), which has 3 operating channels, was placed in the abdomen
      via a 2-cm intraumbilical incision. SILS cholecystectomy was performed
      successfully. Dissection of Calot's triangle and the gallbladder bed was
      performed using a dissector and hook in the right hand without any technical
      problems. CONCLUSION: SIT may confer an advantage over the orthotopic position
      for right-handed surgeons. SILS cholecystectomy can be performed safely in SIT.

PMID- 21902985
TI  - Excision of esophageal duplication cysts with robotic-assisted thoracoscopic
      surgery.
AB  - Esophageal duplication cysts are infrequent anomalies of the gastrointestinal
      tract that are predominantly found in children. The conventional surgical
      approach for removal of these cysts is an open surgery one with a posterolateral
      thoracotomy incision. However, more recently, these cysts have been excised via
      video-assisted thoracoscopic surgery (VATS). In this article, we present 2
      pediatric patients treated with successful excision of an esophageal duplication
      cyst via robotic-assisted thoracoscopic surgery (RATS) using the da Vinci
      surgical system. With robotic technology, precise dissection and complete
      resection of the thoracic mass was achieved without violating the esophageal
      mucosa. There were no complications, and the patients did not require placement
      of a postoperative chest tube. Pathological examination of the mass was
      consistent with an esophageal (foregut) duplication cyst in both cases.

PMID- 21902987
TI  - Prolapsed epiploica of the sigmoid colon after total laparoscopic hysterectomy.
AB  - Prolapsed epiploica of the sigmoid colon through the vaginal cuff is a rare
      finding that has never been reported after total laparoscopic hysterectomy. We
      encountered a case of prolapsed epiploica of the sigmoid colon in a 40-year-old
      female, 4 months status after total laparoscopic hysterectomy. Diagnostic
      laparoscopy demonstrated prolapsed epiploica of the sigmoid colon through a
      dehisced vaginal cuff.

PMID- 21902986
TI  - The last place you would expect to find a gallstone.
AB  - The increasing use of laparoscopic cholecystectomy has led to an increased
      frequency of gallbladder perforation and subsequent gallstone spillage in the
      abdominal cavity. Occasionally unretrieved gallstones can cause infection,
      adhesions, and obstruction. Furthermore, spilt stones can cause erosion into
      adjacent organs and can migrate to distant sites, causing a variety of
      complications. We report the unusual case of a patient who presented with
      spontaneous erosion of gallstones through Grynfeltt's triangle, 1 year after
      laparoscopic cholecystectomy and review the current literature.

PMID- 21902988
TI  - Laparoscopic hysteropexy in a patient with spina bifida and ventriculoperitoneal
      shunt.
AB  - Laparoscopic repair of pelvic organ prolapse in patients with
      ventriculoperitoneal shunts has not been previously described. The optimum
      management of patients with ventriculoperitoneal shunts undergoing laparoscopy is
      uncertain. We describe the case of a 21-year-old female patient with spina bifida
      and ventriculoperitoneal shunt who underwent laparoscopic hysteropexy for severe
      pelvic organ prolapse. The implications of performing laparoscopy on patients
      with ventriculoperitoneal shunts are reviewed along with strategies to reduce
      potential intraoperative complications.

PMID- 21902989
TI  - Removal of an intraperitoneal foreign body using a single port laparoscopic
      procedure.
AB  - BACKGROUND AND OBJECTIVES: To remove a foreign body from the peritoneal cavity in
      laparoscopic surgery, 2 or 3 ports are usually used. We have recently performed
      such a removal using a single 10-mm transumbilical port, a 0-degree laparoscope,
      a Farabeuf retractor, and a laparoscopic grasping forceps. METHODS: Two patients
      with ventriculoperitoneal shunt catheter (V-P shunt) were admitted to our unit
      during the last year. They previously had a shunt catheter implanted for
      hydrocephalus of unknown cause. The complete migration of the
      ventriculoperitoneal shunt catheter into the peritoneal cavity was observed in
      these patients 12 and 7 years after the implantation. The laparoscopic removal of
      the migrated catheter was decided on. Its presence and location were confirmed by
      the use of a 0-degree laparoscope, through a 10-mm trocar port. The catheter was
      held and pulled out using a grasping forceps that was pushed in just beside the
      trocar port. CONCLUSION: The laparoscopic approach enables safe removal of a
      foreign body in the peritoneal cavity. The procedure can be performed using a
      single port.

PMID- 21902990
TI  - Large abdominal wall endometrioma following laparoscopic hysterectomy.
AB  - BACKGROUND: Endometriosis is a common condition in women that affects up to 45%
      of patients in the reproductive age group by causing pelvic pain. It is
      characterized by the presence of endometrial tissue outside the uterine cavity
      and is rarely found subcutaneously or in abdominal incisions, causing it to be
      overlooked in patients with abdominal pain. METHODS: A 45-year-old woman
      presented with lower abdominal pain 2 years following a laparoscopic
      supracervical hysterectomy. She was found to have incidental cholelithiasis and a
      large abdominal mass suggestive of a significant ventral hernia on CT scan.
      RESULTS: Due to the peculiar presentation, surgical intervention took place that
      revealed a large 9cm*7.6cm*6.2cm abdominal wall endometrioma. CONCLUSION:
      Although extrapelvic endometriosis is rare, it should be entertained in the
      differential diagnosis for the female patient who presents with an abdominal mass
      and pain and has a previous surgical history.

PMID- 21902991
TI  - Pre-pubertal presentation of peritoneal inclusion cyst associated with congenital
      lower extremity venous valve agenesis.
AB  - Peritoneal inclusion cysts are uncommon lesions that usually occur in the pelvis
      of reproductive-age females. The case of a 7-year-old girl with an inflamed
      peritoneal inclusion cyst with unusual right paracolic localization and
      congenital lower extremity superficial and deep venous valve agenesis is
      presented. Inflammation of the peritoneal inclusion cyst was responsible for the
      signs of acute abdomen and subsequent presentation at our center. The cystic
      structure was initially diagnosed using ultrasonography, and its complete extent
      (8cm x 6.5cm x 4cm) was evident after magnetic resonance imaging. The minimal
      access approach was opted for to resect the entire cyst from the lateral border
      of the ascending colon. Afterwards, the cyst was punctured to reduce its size and
      to retrieve the cyst wall using an endoscopic specimen retrieval bag. Minimal
      access surgery precautions in this patient with congenital lower extremity venous
      valve agenesis are discussed.

PMID- 21902992
TI  - Postpartum ovarian vein thrombosis.
AB  - BACKGROUND: Ovarian vein thrombosis (OVT) is a rare but potentially serious
      postpartum complication, which occurs in 0.05% to 0.18% of pregnancies and is
      diagnosed on the right side in 80% to 90% of the cases. CASE REPORT: A 32-year
      old woman presented at 15 days postpartum to our emergency department with severe
      abdominal pain, fever, and abdominal distension. Abdominal examination revealed
      right lower quadrant pain with rebound tenderness. The plain abdominal
      radiography evidenced a diffuse fecal stasis; abdominal ultrasound showed the
      presence of free fluid in the Douglas' pouch and between small bowel loops.
      Diagnosis of acute appendicitis was made. The patient immediately underwent
      explorative laparoscopy; at surgery, a woody tumoration consistent with right
      ovarian vein thrombosis was found. Laparoscopic ultrasound confirmed the
      diagnosis. Anticoagulation therapy and antibiotics were instituted. CT-scan
      confirmed the presence of thrombosis up to the vena cava. The patient was
      discharged on postoperative day 4. At 1-month follow-up, she remained stable and
      symptom free. DISCUSSION: Even though postpartum ovarian vein thrombosis is rare,
      recognition and treatment is needed to institute adequate therapy and avoid
      potential serious sequelae. The diagnosis can be established by ultrasound, CT
      scan, and MRI examinations, although, as in the case described, the limitation of
      ultrasound includes obscuration of the gonadic vein by overlying bowel gas.
      CONCLUSION: OVT should be considered in any woman in the postpartum period with
      lower abdominal pain, fever, and leucocytosis.

PMID- 21902993
TI  - Inflammatory pseudotumor of the retroperitoneum removed via a
      retroperitoneoscopic approach.
AB  - BACKGROUND: Inflammatory pseudotumors were mostly encountered in the lung.
      Retroperitoneal inflammatory pseudotumors are relatively rare. Although
      laparoscopic surgery with a modified flank position is widely performed for
      retroperitoneal tumors, we placed the patient in the supine position to maintain
      the normal anatomical view of the retroperitoneal space. We report a case of
      retroperitoneal inflammatory pseudotumor extracted via retroperitoneoscopic
      surgery in the supine position. METHODS AND RESULTS: A 53-year-old man presented
      with back pain and frequent urination. Ultrasonographic examination revealed a
      solid tumor above the urinary bladder. This tumor was diagnosed as a primary
      retroperitoneal tumor by computed tomography, magnetic resonance imaging, and
      angiography. The retroperitoneoscopic procedure was adopted to remove this tumor.
      Histopathologic examination revealed an inflammatory pseudotumor. There was no
      evidence of recurrence 5 years after surgery. CONCLUSIONS: The diagnosis of the
      inflammatory pseudotumor is rarely made before histologic examination. Only
      pathologic examination allows the correct diagnosis. Consequently, most patients
      undergo surgical treatment. A recurrence rate of 25% has been reported for
      inflammatory pseudotumors. Thus, radical resection is needed. The retroperitoneal
      laparoscopic approach with the patient in the supine position is useful for
      surgically treating these primary retroperitoneal tumors located below the level
      of the renal vessels.

PMID- 21902994
TI  - What if the hand piece spring disassembles during robotic radical prostatectomy?
AB  - BACKGROUND AND OBJECTIVES: Robot-assisted laparoscopic radical prostatectomy
      (RALRP) is successfully being performed for treating prostate cancer (PCa).
      However, instrumentation failure associated with robotic procedures represents a
      unique new problem. METHODS: We report the successful completion of RALRP in
      spite of a disassembled hand piece spring during the procedure. A PubMed/Medline
      search was made concerning robotic malfunction and robot-assisted laparoscopic
      radical prostatectomy to discuss our experience. RESULTS: We performed RALRP in a
      60-year-old male patient with localized PCa. During the procedure, the spring of
      the hand piece disassembled, and we were not able to reassemble it. We completed
      the procedure successfully however without fixing the disassembled hand piece
      spring. We were able to grasp tissue and needles when we brought our fingers
      together. The only movement we needed to do was to move fingers apart to release
      tissue or needles caught by robotic instrument. CONCLUSION: Although malfunction
      risk related to the da Vinci Surgical System seems to be very low, it might still
      occur. Sometimes, simple maneuvers may compensate for the failed function as
      occurred in our case. However, patients should be informed before the operation
      about the possibility of converting their procedure to laparoscopic or open due
      to robotic malfunction.

PMID- 21902995
TI  - A clinical study evaluating success of 2 commercially available preveneered
      primary molar stainless steel crowns.
AB  - PURPOSE: To evaluate the success of posterior NuSmile((r)) and KinderTMKrown and
      to determine the level of parental satisfaction with this treatment option.
      METHODS: Forty-eight crowns were placed in 18 children with a mean age of 5
      years. A split mouth design was used. Each participant randomly received each
      crown type on 2 or 4 pair matched molars. Two trained operators completed all
      treatments. Two additional trained and calibrated clinicians blindly re-evaluated
      crowns according to specified variables. A visual analogue scale was used to
      determine parental satisfaction. Examiner reliability was determined by Cohen's
      kappa scores and results were analysed statistically using Fisher's exact test.
      RESULTS: All crowns were retained after 12 months with no statistical difference
      in the clinical and radiographic success of posterior NuSmile((r)) and
      KinderTMKrowns. Overall success was high with 81% of facings intact and 83% free
      of gingival inflammation after 12 months. Radiographically, 81% were successful.
      Veneer facing wear was significantly more likely to occur with opposing crowns
      (P=.02). Parental satisfaction was excellent with a mean score of 9.3 out of 10.
      CONCLUSIONS: These crowns combine the durability of conventional stainless steel
      crowns with improved esthetics and are proposed as a suitable alternative where
      esthetic demand is increased.

PMID- 21902996
TI  - Antibacterial effects of chemomechanical instrumentation and calcium hydroxide in
      primary teeth with pulp necrosis.
AB  - PURPOSE: This study's purposes were to: evaluate the antibacterial effect of
      chemomechanical instrumentation and a calcium hydroxide-based dressing in primary
      teeth with pulp necrosis secondary to trauma; and detect the presence of
      Fusobacterium nucleatum and black-pigmented rods in the canals of these teeth.
      METHODS: Microbiological sample collections (MSCs) were obtained: after coronal
      access to the canals of primary incisors (in 18 teeth; MSC 1); after
      chemomechanical instrumentation (in 10 teeth; MSC 2); and 72 hours after removal
      of intracanal medication (in 18 teeth; MSC 3). These samples were sent for
      microbiological processing. The results were analyzed statistically via chi
      square, analysis of variance, and Games-Howell tests (P<.05). RESULTS: Micro
      organisms were isolated in approximately 94%, 10%, and 83% of canals,
      respectively, in MSCs 1, 2, and 3. There was a statistically significant
      difference only between MSCs 1 and 2 (P<.03). F nucleatum and black-pigmented
      rods were detected in approximately 56% and 11% of canals in MSC 1, respectively.
      CONCLUSION: Chemomechanical instrumentation and calcium hydroxide-based dressing
      have an anti-bacterial effect by significantly reducing the number of micro
      organisms in the main root canal. They showed a limited efficacy, however, and
      did not prevent bacterial regrowth after endodontic therapy in primary teeth with
      pulp necrosis secondary to trauma.

PMID- 21902997
TI  - Radiographic evaluation of alveolar bone height in the primary dentition: a
      retrospective follow-up study.
AB  - PURPOSE: The aim of this retrospective follow-up study was to verify the distance
      between the cementoenamel junction (CEJ) and the alveolar bone crest (ABC) in
      bitewing radiographs. METHODS: Radiographs were digitized and divided into groups
      by: age, proximal crown surface status (sound->sound and unsound->unsound),
      tooth, and timing of radiograph. The CEJ-ABC distances were measured on the
      distal surface of the first primary molar and/or the mesial surface of the second
      lower primary molar, using the Image Tool software. RESULTS: The results revealed
      interactions between the following variables: timing of radiograph-age, age
      tooth, timing of radiograph - proximal crown surface status and age- proximal
      crown surface status. It has been detected that CEJ-ABC distances have
      significantly increased with time, particularly in terms of assessment of primary
      lower first molars. However, this increase is greater in unsound when compared to
      sound surfaces. CONCLUSION: This study suggests that an increase in the CEJ-ABC
      distance is directly associated with aging in a normal periodontium in the
      primary dentition and that the presence of unsound surfaces can be a risk
      indicator for the development of alveolar bone loss.

PMID- 21902998
TI  - Long-term outcomes of primary tooth pulpectomy with and without smear layer
      removal: a randomized split-mouth clinical trial.
AB  - PURPOSE: The aim of this study was to evaluate, via clinical and radiographic
      assessment, pulpectomy outcomes performed on primary anterior teeth both with and
      without a citric acid solution to enhance smear layer removal. METHODS: Patients
      with a matched pair of primary incisors (split-mouth design) with irreversible
      pulp changes were selected. A total of 36 teeth (18 children) received
      pulpectomies and were followed for 36 months. Pulpectomies were performed using
      sodium hypochlorite and saline solution as canal irrigants; during the last
      irrigation, the tooth was randomly selected to receive ( Group 1) or not receive
      (Group 2) the citric acid solution for smear layer removal. The roots were filled
      with ZOE paste. RESULTS: Overall pulpectomy success was 90.6%. Cases with smear
      layer removal were successful 82.3% of the time; those without smear layer
      removal, 88.2%, and there were no statistical differences (P=1.00). CONCLUSION:
      Pulpectomy with smear layer removal in primary incisors exhibited, after 36
      months, a high success rate; however, comparable results were obtained when the
      smear layer was not removed.

PMID- 21902999
TI  - Factors related to postoperative discomfort in young children following dental
      rehabilitation under general anesthesia.
AB  - PURPOSE: This study, conducted in ambulatory surgical centers, was a response to
      queries from pediatric dentists who wondered if postoperative discomfort in their
      patients treated for early childhood caries under general anesthesia was related
      to specific dental procedures. The purpose of this study was to identify factors
      related to the occurrence and severity of postoperative discomfort. METHODS:
      Subjects were children younger than 7 years old. The faces, legs, activity, cry,
      consolability pain assessment tool measured discomfort immediately
      postoperatively; the dental discomfort questionnaire (DDQ-8) measured discomfort
      preoperatively and after treatment. Data was analyzed with bivariate tests and
      hierarchical linear multiple regression. RESULTS: Of the 160 participants (52.9+/
      15.0 months old), approximately 51% had preoperative dental discomfort (DDQ-8
      score=>3). The proportion with discomfort had significantly decreased to 27% by
      days 2 to 5. Immediate discomfort in recovery was influenced by number of crowns
      and space maintainers and inversely by the length of postoperative sleep. Dental
      discomfort in the first week postoperatively was predicted by amount of
      preoperative discomfort, length of sleep in recovery, and not resuming a regular
      diet on Day 1. CONCLUSION: In these children, discomfort after treatment was
      mild, decreased over time, and, other than immediately postoperatively, was not
      related to specific dental procedures.

PMID- 21903000
TI  - Sodium hypochlorite pulpotomies in primary teeth: a retrospective assessment.
AB  - PURPOSE: In 2007, the University of Iowa's advanced training program in pediatric
      dentistry replaced the traditional formocresol vital pulpotomy technique with a
      5% sodium hypochlorite (NaOCl) technique. The purpose of this study was to
      evaluate the clinical/radiographic success over 21 months of 5% NaOCl as the
      medicament in primary molar pulpotomies compared to published data for
      formocresol and ferric sulfate pulpotomies. METHODS: A retrospective chart audit
      was performed to evaluate results for all primary molar pulpotomies completed
      during a 12-month period using NaOCl. Dental records were reviewed for clinical
      and radiographic findings subsequent to pulp therapy. Clinical and radiographic
      criteria used to determine pulpotomy success were based on scientific literature.
      RESULTS: One hundred ninety-two NaOCl primary molar pulpotomies were completed in
      118 patients; 131 (68%) primary molars from 77 children were available for follow
      up examination (mean time since pulpotomy=10.5 months). NaOCl pulpotomies had a
      95% clinical and 82% overall radiographic success rate. External root resorption
      was the most common pathologic finding. Pulpotomy success diminished over time.
      CONCLUSIONS: Clinical and radiographic success rates in this study on NaOCl
      pulpotomies are comparable to formocresol and ferric sulfate pulpotomies reported
      in the literature. Further study with longer observation periods is warranted.

PMID- 21903001
TI  - Factors associated with sealant outcome in 2 pediatric dental clinics: a
      multivariate hierarchical analysis.
AB  - PURPOSE: This study's purpose was to determine whether one-time sealants placed
      by pediatric dental residents vs dental students have different outcomes. The
      effect of isolation technique, behavior, duration of follow-up, and caries
      history was also examined. METHODS: Records from 2 inner-city pediatric dental
      clinics were audited for 6- to 10-year-old patients with a permanent first molar
      sealant with at least 2 years of follow-up. A successful sealant was a one-time
      sealant that received no further treatment and was sealed or unsealed but not
      carious or restored at the final audit. RESULTS: Charts from 203 children with
      481 sealants were audited. Of these, 281 sealants were failures. Univariate
      analysis revealed longer follow-up and younger age were associated with sealant
      failure. Operator type, child behavior, and isolation technique were not
      associated with sealant failure. After adjusting for follow-up duration,
      increased age at treatment reduced the odds of sealant failure while a history of
      caries reduced the protective effect of increased age. After adjusting for these
      factors, practitioner type, behavior, and type of isolation were not associated
      with sealant outcome in multivariate analysis. CONCLUSIONS: Age at sealant
      placement, history of caries prior to placement, and longer duration of follow-up
      are associated with sealant failure.

PMID- 21903002
TI  - Treatment of anterior crossbite in the primary dentition with esthetic crowns:
      report of 3 cases.
AB  - Anterior crossbite is a sagittal malocclusion occurring in approximately 4 to 5%
      of children with primary dentition. Although self-correction may occur, treating
      an anterior crossbite as early as possible has been proposed to prevent problems
      in the transitional and permanent dentitions. The purpose of this paper is to
      present an optional restorative treatment used in 3 cases where an anterior
      crossbite was treated by restoring the primary maxillary incisors with esthetic
      pediatric strip crowns. In all 3 cases, the crossbite was successfully treated by
      using the proposed technique over 1 to 2 weeks. A 6-month follow-up showed that
      the occlusion stabilized into a sagittal normal relationship, permitting normal
      dentofacial growth and development to continue. The technique presented here can
      be added to the armamentarium of pediatric dentists and general practitioners to
      correct anterior crossbites diagnosed in the primary dentition.

PMID- 21903003
TI  - Assessment of noise exposures in a pediatric dentistry residency clinic.
AB  - PURPOSE: In addition to sounds from dental equipment, pediatric dentists are
      exposed to noise produced by precooperative and/or noncooperative children. The
      purpose of this study was to evaluate the daily personal noise exposure of a
      pediatric dentistry resident while treating children in a teaching clinic to
      determine both comprehensive noise doses and peak noise occurrences as well as to
      assess the risk for noise-induced hearing loss. METHODS: A noise dosimeter (Noise
      Pro DLX) was used to measure the total personal noise exposure dose using the
      Occupational Safety and Health Administration (OSHA) Hearing Conservation
      Amendment criteria and the US National Institute for Occupational Safety and
      Health (NIOSH) occupational noise exposure revised criteria. Comprehensive noise
      doses for 31 days were obtained for a single resident. RESULTS: OSHA and NIOSH
      allowable limits were not exceeded during any one day in the study period. Noise
      levels during crying episodes, however, were higher than the reported noise
      levels of dental instruments and reached maximum levels of 112.9 dBA.
      CONCLUSIONS: Noise levels to which the pediatric dental resident was exposed fell
      below the Occupational Safety and Health Administration's and National Institute
      for Occupational Safety and Health's damage-risk thresholds for noise-induced
      hearing loss.

PMID- 21903004
TI  - Dental implications of osteogenesis imperfecta: treatment with IV bisphosphonate:
      report of a case.
AB  - Osteogenesis imperfect (OI) is a group of genetically diverse connective tissue
      disorders. Bisphosphonates therapy to manage bone fragility, a now common medical
      therapy for OI, can increase the risk of bisphosphonate-associated osteonecrosis
      of the jaws. In this report, a 6 1/2 year child, who was receiving bisphosphonate
      therapy for OI, underwent full mouth dental rehabilitation in the operating room
      while under general anesthesia. The child had numerous teeth restored and
      multiple primary molar extractions. The patient, who received prophylactic
      antibiotics intraoperatively, demonstrated no clinical signs of bisphosphonate
      associated osteonecrosis when seen at follow-up. Although bisphosphonate
      osteonecrosis is a possible sequel in children who receive multiple extractions,
      no clinical signs were manifested in our patient, who required multiple primary
      tooth extractions along with restorative treatment under general anesthesia.
      While no dental guidelines have been developed to manage OI children having been
      treated with bisphosphonates, consent for extractions should include the risk of
      bone necrosis and careful post-operative observation to monitor wound healing.

PMID- 21903007
TI  - Letter to the editor. Re: SCIRehab series, J Spinal Cord Med.2011(Mar);34(2).
      Rehabilitation of the diaphragm - an opportunity.

PMID- 21903005
TI  - A survey study of sedation training in advanced pediatric dentistry programs:
      thoughts of program directors and students.
AB  - PURPOSE: The purpose of this study was to survey program directors and students
      of advanced pediatric dentistry training programs in the United States on
      sedation issues. METHODS: Surveys were sent to the target audiences. Questions
      contained response categories ranging from fill-in-the-blank, Likert-order scale
      style, and categorical. The surveys resided on SurveyMonkey. A cover letter
      emphasizing such issues as anonymity of responses was sent via e-mail to
      participants using the American Academy of Pediatric Dentistry listserv. The
      responses were downloaded and subsequently analyzed using SPSS statistical
      software. RESULTS: Data were obtained from 49% of program directors and 17% of
      students. Experience with different routes of sedative administration varied from
      "none" (even with the oral route) to "significant." Oral midazolam was the most
      often used route and sedative. Restraint was reportedly used by the majority of
      programs. CONCLUSIONS: Strategies should be developed to strengthen consistency
      of competencies in sedation practices across academic training programs.

PMID- 21903009
TI  - Disaster preparedness and response practices among providers from the Veterans
      Health Administration and Veterans with spinal cord injuries and/or disorders.
AB  - OBJECTIVES: Few empirical studies have examined the disaster preparedness and
      response practices of individuals with spinal cord injuries and/or disorders
      (SCI/D) and the healthcare providers who serve them. This study was conducted to
      understand the experiences of Veterans Health Administration (VHA) providers and
      Veterans with SCI/D in recent natural disasters, and to identify lessons learned
      for disaster preparedness and response in the context of SCI/D. DESIGN: Semi
      structured interviews were conducted with providers and Veterans recruited
      through seven VHA facilities that had sustained a disaster since 2003. Audio
      recordings of the interviews were transcribed; transcripts were analyzed using
      constant comparative techniques. RESULTS: Forty participants completed an
      interview, including 21 VHA SCI/D providers and 19 Veterans with SCI/D. Disasters
      experienced by participants were weather related. While many Veterans were
      evacuated or admitted to nearby VHA facilities, others chose to stay in their
      communities. All facilities had formal disaster plans and engaged in related
      training; however, participants explained that many aspects of a response take
      shape 'in the moment,' and must address both provider and Veteran needs.
      Dispersion of resources hindered well-coordinated care, but effective
      communication, teamwork, advanced warnings, and VHA's electronic medical record
      facilitated efforts. CONCLUSIONS: Even in the case of thorough planning, Veterans
      with SCI/D and their healthcare providers are faced with pressing needs during
      disasters, and identifying strategies to coordinate care is critical. The lessons
      learned are intended to inform the efforts of healthcare providers who may be
      involved in the care of individuals with SCI/D in future disasters.

PMID- 21903010
TI  - Comparison of training methods to improve walking in persons with chronic spinal
      cord injury: a randomized clinical trial.
AB  - OBJECTIVE: To compare two forms of device-specific training - body-weight
      supported (BWS) ambulation on a fixed track (TRK) and BWS ambulation on a
      treadmill (TM) - to comprehensive physical therapy (PT) for improving walking
      speed in persons with chronic, motor-incomplete spinal cord injury (SCI).
      METHODS: Thirty-five adult subjects with a history of chronic SCI (>1 year; AIS
      'C' or 'D') participated in a 13-week (1 hour/day; 3 days per week) training
      program. Subjects were randomized into one of the three training groups. Subjects
      in the two BWS groups trained without the benefit of additional input from a
      physical therapist or gait expert. For each training session, performance values
      and heart rate were monitored. Pre- and post-training maximal 10-m walking speed,
      balance, muscle strength, fitness, and quality of life were assessed in each
      subject. RESULTS: All three training groups showed significant improvement in
      maximal walking speed, muscle strength, and psychological well-being. A
      significant improvement in balance was seen for PT and TRK groups but not for
      subjects in the TM group. In all groups, post-training measures of fitness,
      functional independence, and perceived health and vitality were unchanged.
      CONCLUSIONS: Our results demonstrate that persons with chronic, motor-incomplete
      SCI can improve walking ability and psychological well-being following a
      concentrated period of ambulation therapy, regardless of training method.
      Improvement in walking speed was associated with improved balance and muscle
      strength. In spite of the fact that we withheld any formal input of a physical
      therapist or gait expert from subjects in the device-specific training groups,
      these subjects did just as well as subjects receiving comprehensive PT for
      improving walking speed and strength. It is likely that further modest benefits
      would accrue to those subjects receiving a combination of device-specific
      training with input from a physical therapist or gait expert to guide that
      training.

PMID- 21903011
TI  - Vertebral fracture secondary to suicide attempt: demographics and patient outcome
      in a Scottish spinal rehabilitation unit.
AB  - OBJECTIVE: To establish occurrence, method of injury, length of stay (LOS),
      psychiatric diagnosis, rehabilitation outcome, and demographic data for those
      admitted to a Scottish Spinal Injuries Rehabilitation Unit as a consequence of
      deliberate self-harm (DSH). DESIGN: A retrospective audit of case-notes and
      electronic databases of admissions and rehabilitation outcome in a spinal cord
      injury (SCI) unit where the mechanism of injury was (DSH). RESULTS: Forty-six (44
      having detailed data available) patients were identified with 95% of injuries
      resulting from falls. Thirty-six people had pre-existing mental health problems
      (82%) with 15 (34%) having this diagnosis established shortly after admission.
      Seventy-five per cent received follow-up from mental health services. Ninety-five
      per cent returned to their pre-injury (or similar) residence. LOS and functional
      independence measure (FIM) for the DSH group were compared with a non-DSH group.
      No differences were found in those with SCI. LOS was significantly longer in the
      patients with vertebral fracture and no neurological impairment (32 versus 22
      days). Sixty-four per cent of those who had self-harmed had substance dependence
      problems. The predominance of falls (63%) occurred in a residential setting.
      Annual admissions due to individuals self-harming were stable across the studied
      period. CONCLUSIONS: Spinal column fracture in the DSH group is predominantly
      caused by falls. High levels of mental health and substance abuse problems are
      noted necessitating formal mental health assessment and follow-up. DSH as a
      mechanism for injury appears to have a significant impact on LOS only if the
      patient has fracture without SCI. Immediate rehabilitation outcomes are similar
      to that of non-DSH group.

PMID- 21903012
TI  - Epidemiological profile of 239 traumatic spinal cord injury cases over a period
      of 12 years in Tianjin, China.
AB  - STUDY DESIGN: Hospital-based retrospective review. OBJECTIVE: To describe the
      epidemiological characteristics and trends of traumatic spinal cord injury in
      Tianjin, China. SETTING: Tianjin Medical University General Hospital. METHODS:
      Medical records of 239 patients with traumatic spinal cord injury admitted to a
      general hospital from 1998 to 2009 were reviewed. Variables included gender, age,
      marital status, occupation, etiology, time of injury, level, and severity of
      injury. Epidemiological characteristics of different countries were compared.
      RESULTS: Over this period, the mean age of patients with traumatic spinal cord
      injury was 45.4 +/- 14.1 years, and the male/female ratio was 4.6:1. In all,
      86.2% were married. The leading cause was fall (52.3%), followed by motor vehicle
      collision (36.4%). The most common injury site was the cervical spinal cord,
      accounting for 82.0%. Incomplete tetraplegia made up for 59.4%, followed by
      complete tetraplegia (22.6%). Eight patients died after operation, six of whom
      died from respiratory complications. CONCLUSION: The results of this study are in
      accordance with that of most other developing countries; falls and motor vehicle
      collisions were the two leading causes, but the mean age was older. Percentage of
      the aged with traumatic spinal cord injury was increasing. The low-falls group
      tended to expand over this period. All these data indicated that the preventive
      programs should focus on the traffic accidents and falls, and more attention
      should be paid to the aged for the vulnerability to low fall.

PMID- 21903014
TI  - Use of on-demand video to provide patient education on spinal cord injury.
AB  - BACKGROUND/OBJECTIVE: Persons with chronic spinal cord injury (SCI) have a high
      lifetime need for ongoing patient education to reduce the risk of serious and
      costly medical conditions. We have addressed this need through monthly in-person
      public education programs called SCI Forums. More recently, we began videotaping
      these programs for streaming on our website to reach a geographically diverse
      audience of patients, caregivers, and providers. DESIGN/METHODS: We compared
      information from the in-person forums to that of the same forums shown streaming
      on our website during a 1-year period. RESULTS: Both the in-person and Internet
      versions of the forums received high overall ratings from individuals who
      completed evaluation forms. Eighty-eight percent of online evaluators and 96% of
      in-person evaluators reported that they gained new information from the forum; 52
      and 64% said they changed their attitude, and 61 and 68% said they would probably
      change their behavior or take some kind of action based on information they
      learned. Ninety-one percent of online evaluators reported that video is better
      than text for presenting this kind of information. CONCLUSION: Online video is an
      accessible, effective, and well-accepted way to present ongoing SCI education and
      can reach a wider geographical audience than in-person presentations.

PMID- 21903013
TI  - Comparison of 24-hour cardiovascular and autonomic function in paraplegia,
      tetraplegia, and control groups: implications for cardiovascular risk.
AB  - BACKGROUND: Fluctuations in 24-hour cardiovascular hemodynamics, specifically
      heart rate (HR) and blood pressure (BP), are thought to reflect autonomic nervous
      system (ANS) activity. Persons with spinal cord injury (SCI) represent a model of
      ANS dysfunction, which may affect 24-hour hemodynamics and predispose these
      individuals to increased cardiovascular disease risk. OBJECTIVE: To determine 24
      hour cardiovascular and ANS function among individuals with tetraplegia (n=20;
      TETRA: C4-C8), high paraplegia (n=10; HP: T2-T5), low paraplegia (n=9; LP: T7
      T12), and non-SCI controls (n=10). Twenty-four-hour ANS function was assessed by
      time domain parameters of heart rate variability (HRV); the standard deviation of
      the 5-minute average R-R intervals (SDANN; milliseconds/ms), and the root-mean
      square of the standard deviation of the R-R intervals (rMSSD; ms). Subjects wore
      24-hour ambulatory monitors to record HR, HRV, and BP. Mixed analysis of variance
      (ANOVA) revealed significantly lower 24-hour BP in the tetraplegic group;
      however, BP did not differ between the HP, LP, and control groups. Mixed ANOVA
      suggested significantly elevated 24-hour HR in the HP and LP groups compared to
      the TETRA and control groups (P<0.05); daytime HR was higher in both paraplegic
      groups compared to the TETRA and control groups (P<0.01) and nighttime HR was
      significantly elevated in the LP group compared to the TETRA and control groups
      (P<0.01). Twenty-four-hour SDANN was significantly increased in the HP group
      compared to the LP and TETRA groups (P<0.05) and rMSSD was significantly lower in
      the LP compared to the other three groups (P<0.05). Elevated 24-hour HR in
      persons with paraplegia, in concert with altered HRV dynamics, may impart
      significant adverse cardiovascular consequences, which are currently
      unappreciated.

PMID- 21903015
TI  - Comparison of rehabilitation outcomes following vascular-related and traumatic
      spinal cord injury.
AB  - BACKGROUND: Previous studies have noted similar outcomes between vascular-related
      spinal cord injury (VR-SCI) and those with traumatic SCI (T-SCI), despite
      significant difference in their demographics and clinical presentation (age,
      level of injury (LOI), and degree of incompleteness). OBJECTIVES: To review
      demographic and clinical presentation of VR-SCI and to compare outcomes with a
      matched group with T-SCI. Design Analysis of 10-year prospective data collection
      including 30 consecutive patients admitted to an SCI rehabilitation unit with VR
      SCI and comparison with 573 patients with T-SCI. Outcomes were further analyzed
      comparing VR-SCI to T-SCI (n=30), matched for age, LOI, and ASIA (American Spinal
      Injury Association) Impairment Scale (AIS). SETTING: A level 1 tertiary
      university trauma center. MAIN OUTCOME MEASURES: Functional independence measure
      (FIM) score changes from admission to discharge. Secondary outcome measures
      included admission and discharge FIM scores, FIM efficiency, rehabilitation
      length of stay (LOS), and discharge disposition. RESULTS: Overall, individuals
      with VR-SCI were more likely (P<0.0001) to be older (mean age 57.2 vs. 40.0
      years) and have paraplegia (87 vs. 48%) than those with T-SCI. Common etiologies
      for VR-SCI were post-surgical complication (43%), arteriovenous malformation
      (17%), aortic dissection (13%), and systemic hypotension (13%). Common region of
      injury and AIS classification in VR-SCI was thoracic (73%) and AIS C (33%).
      Common SCI-related complications in VR-SCI included neurogenic bowel/bladder
      (93%), urinary tract infection (73%), pain (67%), pressure ulcers (47%), and
      spasticity (20%). Matched-group outcome comparisons did not reveal significant
      differences in FIM change, FIM efficiency, LOS, or disposition between VR-SCI and
      T-SCI. CONCLUSION: VR-SCI leads to significant disability and is associated with
      common secondary SCI complications as well as medical co-morbidities. This study
      notes differing demographic and injury characteristics between VR-SCI and T-SCI
      groups. However, when matched for these differences, rehabilitation functional
      outcomes were not significantly different between the two groups.

PMID- 21903016
TI  - Clinical assessment of obesity in persons with spinal cord injury: validity of
      waist circumference, body mass index, and anthropometric index.
AB  - OBJECTIVE: To study the relationship of waist circumference (WC) and
      bioelectrical impedance analysis (BIA) and degree of agreement between
      anthropometric index (AI) and BIA, using BIA as a reference or 'gold standard'.
      The second objective is to study the relationship between body mass index (BMI)
      and BIA in subjects with spinal cord injury (SCI). STUDY DESIGN: Comparative
      cross-sectional study. SETTING: Convenience sample at outpatient clinic of spinal
      cord center. OUTCOME MEASURES: Estimation of obesity was made in 23 men with
      motor complete paraplegia (>1 year post-injury). Bland and Altman statistics were
      used to define level of agreement between AI and BIA, Pearson's r to describe
      correlation between WC and BIA and BMI and BIA. RESULTS: Good agreement between
      BIA and AI with a small systematic difference in fat mass (FM) (mean difference: 
      0.28%, Pearson's r: 0.91) was found. The correlation between WC and the BIA (%
      FM) was very high (Pearson's r: 0.83). The correlation between WC and BMI (% FM)
      was just over moderate (Pearson's r: 0.51). CONCLUSION: AI seems to be a valid
      proxy measure to estimate obesity in males living with SCI. Measurement of
      obesity in persons with SCI based on WC is promising. BMI showed not to be valid
      to estimate obesity in persons with SCI.

PMID- 21903017
TI  - Association between seeking oral health information online and knowledge in
      adults with spinal cord injury: a pilot study.
AB  - OBJECTIVE: To characterize adults with spinal cord injury (SCI) who seek oral
      health information online, and investigate whether seeking oral health
      information online is associated with oral health knowledge and behaviors.
      METHODS: An online oral health survey was posted on the South Carolina Spinal
      Cord Injury Association website. Respondents were 192 adult residents of the US
      ages 19-83 years who identified themselves as having SCI occurring at least 1
      year before the survey date. RESULTS: About 12% (n=23) of the respondents
      searched oral health information online in the past 12 months. Significant
      associations between the proportion of respondents who searched for oral health
      information online and socio-demographic and the proportion of respondents who
      engaged in various oral health behaviors were not detected. However,
      multivariable logistic regression indicated that respondents who searched oral
      health information online in the past 12 months have 3.4 times the odds of
      possessing adequate oral health knowledge compared to respondents who did not
      search oral health information online (adjusted odds ratio=3.41, 95% confidence
      interval = 1.35, 8.62, P=0.01). CONCLUSIONS: Given the significant association
      between seeking oral health information online and adequate oral health
      knowledge, this study suggests that online oral health information may be a
      potential avenue for dental health professionals to supplement oral health
      education in adults with SCI.

PMID- 21903018
TI  - Spontaneous epidural hematoma of thoracic spine presenting as Brown-Sequard
      syndrome: report of a case with review of the literature.
AB  - BACKGROUND: Spontaneous spinal epidural hematoma (SSEH) is an uncommon clinical
      entity. It produces a severe neurological deficit and prompt decompression is
      usually the first choice of treatment. Brown-Sequard syndrome is commonly seen in
      the setting of spinal trauma or an extramedullary spinal neoplasm, but rarely
      caused by SSEH. METHODS: Case report and literature review. FINDINGS: A
      previously healthy man presented with Brown-Sequard syndrome below T5-T6 cord
      segment secondary to spontaneous epidural hematoma. He opted for conservative
      treatment, which was followed by rapid resolution. CONCLUSIONS: Although Brown
      Sequard syndrome as a presenting feature of SSEH is rare, it does exist in
      exceptional case, which should be taken into consideration for differential
      diagnosis. Prompt surgical decompression is an absolute surgical indication
      widely accepted for patient with progressive neurological deficit. However, SSEH
      presenting with incomplete neurological insult such as Brown-Sequard syndrome
      might have a benign course. Successful non-operative management of this problem
      does not make it a standard of care, and surgical decompression remains the
      standard treatment for SSEH.

PMID- 21903019
TI  - A new vesicle-loaded hydrogel system suitable for topical applications:
      preparation and characterization.
AB  - PURPOSE. Aim of this research was to prepare and study drug release from a new
      formulation consisting of non ionic surfactant vesicular structures, niosomes
      (NSVs), loaded with model molecules calcein (CALC), nile red (NR), ibuprofen
      (IBU) or caffeine (CAFF), and embedded in a hydrogel matrix. METHODS. The system
      locust bean gum/xanthan (1:1), prepared at 60  degrees C, was used to entrap the
      vesicles (Tween 20/cholesterol 1:1), loaded with guest molecules and the release
      profiles were detected at 32  degrees C. The hydrogel systems were characterized
      by means of scanning electron microscopy; niosomes were characterized by means of
      size and ?-potential measurements. RESULTS. Size measurements showed that a
      slight increase in vesicle dimensions occurs after inclusion of CALC or CAFF
      (hydrophilic molecules) in the vesicular structures. ?-potential measurements
      showed that the inclusion of these molecules did not significantly modify the
      surface charge of empty vesicles. This was probably related to an almost
      negligible drug adsorption on the vesicle surface. The release from the niosomes
      gel systems of two probes (CALC and NR) showed that the diffusion of CALC through
      the gel was not affected by the niosome entrapment while for NR, the presence of
      vesicles was crucial. The release profiles from niosomes-gel systems and from the
      hydrogel alone of model drugs, CAFF and IBU, showed an appreciable difference
      between the two drugs: the more hydrophilic CAFF was released much faster than
      IBU. In all release studies turbidity, dimension and ?-potential analyses
      indicated that the loaded niosomes were released by the hydrogel matrix without
      being damaged. CONCLUSIONS. The reported in vitro experiments show the capability
      of the novel formulation to combine the qualities of both chosen single systems,
      i.e. the niosomes and the polymeric network. The hydrogel shows a protective
      effect on vesicle integrity and leads to a slow release of the loaded model
      molecules from the polysaccharidic system. This article is open to POST
      PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by
      clicking on ABSTRACT on the issue's contents page.

PMID- 21903020
TI  - Bereavement and the diagnosis of major depressive episode in the National
      Epidemiologic Survey on Alcohol and Related Conditions.
AB  - OBJECTIVE: Bereavement-related depression is excluded from a diagnosis of major
      depressive episode (MDE) in DSM-IV, unless the syndrome is prolonged or
      complicated. The objective of this study is to assess the validity of the
      bereavement exclusion by comparing characteristics of bereavement-related
      episodes that are excluded from a diagnosis and bereavement-related episodes that
      qualify for a diagnosis (complicated bereavement) to MDE. METHOD: We used data
      from 2 waves of the National Epidemiologic Survey on Alcohol and Related
      Conditions (n = 43,093) to compare bereavement-excluded depression and
      complicated bereavement to MDE with respect to indicators of preexisting risk for
      psychopathology (antecedent indicators) and indicators of disorder severity
      measured at baseline and at the study's 3-year follow-up interview (consequent
      indicators). The primary outcome measure was the Alcohol Use Disorder and
      Associated Disabilities Interview Schedule-IV. RESULTS: Compared to individuals
      with MDE, individuals with bereavement-excluded depression had lower risks of
      preexisting psychiatric disorders (eg, 0.44 lower odds of social phobia, P =
      .006), fewer depressive episodes (recurrence rate 0.37 times lower, P < .001),
      less psychosocial impairment (P < .001), a 0.18 times lower odds of seeking
      treatment (P < .001), and a lower risk of psychiatric disorders during a 3-year
      follow-up period. Unexpectedly, this same pattern of differences was observed
      between individuals with complicated bereavement and MDE. CONCLUSIONS: Despite
      the presence of a clinically significant depressive episode, bereavement-excluded
      depression is in many ways less indicative of psychopathology than MDE. However,
      complicated bereavement was more similar to bereavement-excluded depression than
      to MDE. We therefore question whether the DSM-IV criteria validly distinguish
      between nondisordered loss reactions (bereavement-excluded depression),
      pathological loss reactions (complicated bereavement), and nonloss-related MDE.

PMID- 21903022
TI  - First-onset psychosis occurring in the postpartum period: a prospective cohort
      study.
AB  - OBJECTIVE: To prospectively characterize a cohort of patients for whom first
      lifetime episode of psychosis occurs in the postpartum period. METHOD: Included
      in the study were 51 women admitted to an inpatient facility for postpartum
      psychosis and a population-based control group (n = 6,969). All patients received
      naturalistic treatment using the sequential addition of benzodiazepines,
      antipsychotics, and lithium. A clinician-administered questionnaire and parallel
      history provided information about obstetric history, pregnancy, delivery,
      breastfeeding, neonatal outcomes, and onset of the disease. Clinical remission
      was defined as the absence of psychotic, manic, and depressive symptoms for at
      least 1 week. The primary outcome measure was the Clinical Global Impressions
      Severity scale. The study was conducted from 2005 to 2009. RESULTS: Compared to
      the general population sample, women with postpartum psychosis had a
      significantly higher incidence of primiparity (OR = 2.90; 95% CI, 1.49-5.67) but
      had no significant differences in delivery-related, lactational, or neonatal
      related risk factors. The median onset of psychiatric symptoms occurred at 8
      days' postpartum (interquartile range [IQR], 5-14), and median duration of
      episode was 40 days (IQR, 23-69). Patients with prominent depressive symptoms had
      a significantly later onset (P = .01) of psychosis and a longer duration of
      episode (P < .01) than patients without depressive symptoms. Psychotic symptoms
      were mood-incongruent in 64.7% of patients. CONCLUSIONS: In contrast to other
      findings related to postpartum psychosis in bipolar patients, no delivery
      related, neonatal-related, or lactational risk factors could be identified.
      Further, our findings of a delayed onset and mood incongruence of postpartum
      psychotic symptoms markedly contrasts with that of patients with a previous
      history of bipolar disorder. These results suggest that women with psychosis
      limited to the postpartum period might have a distinct risk profile and
      phenomenology.

PMID- 21903021
TI  - Raloxifene as an adjunctive treatment for postmenopausal women with
      schizophrenia: a double-blind, randomized, placebo-controlled trial.
AB  - OBJECTIVE: The potential therapeutic utility of estrogens in schizophrenia is
      increasingly being recognized. Raloxifene, a selective estrogen receptor
      modulator, appears to act similarly to conjugated estrogens on dopamine and
      serotonin brain systems and may be a better option since it lacks the possible
      negative effects of estrogen on breast and uterine tissue. In this study, we
      assess the utility of raloxifene as an adjunctive treatment for negative symptoms
      and other psychotic symptoms in postmenopausal women with schizophrenia. METHOD:
      This was a 12-week, double-blind, randomized, placebo-controlled study. Patients
      were recruited from both the inpatient and outpatient departments of Parc
      Sanitari Sant Joan de Deu, Barcelona, Spain, and Corporacio Sanitaria Parc Tauli,
      Sabadell, Spain. Thirty-three postmenopausal women with schizophrenia (DSM-IV
      criteria) who exhibited prominent negative symptoms were randomized to either
      adjunctive raloxifene (16 women; mean age = 60.14 years, SD = 6.41 years) or
      adjunctive placebo (17 women; mean age = 62.66 years, SD = 4.54 years) for 12
      weeks. The period of recruitment lasted from January 2005 through June 2009.
      Psychopathological symptoms were assessed at baseline and weeks 4, 8, and 12 by
      means of the Positive and Negative Syndrome Scale. RESULTS: The addition of
      raloxifene (60 mg/d) to regular antipsychotic treatment significantly reduced
      negative (P = .044), positive (P = .031), and general psychopathological (P =
      .045) symptoms during the 12-week trial as compared with women receiving placebo.
      CONCLUSIONS: Raloxifene as an adjuvant treatment in postmenopausal women with
      schizophrenia who exhibit prominent negative symptoms appears to be useful in
      improving negative, positive, and general psychopathological symptoms. If more
      extensive and longer-term studies confirm and expand upon these positive results,
      the use of raloxifene could be recommended in postmenopausal patients with
      schizophrenia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01041092.

PMID- 21903024
TI  - The clinical process in psychiatry: a clinimetric approach.
AB  - OBJECTIVE: The aim of this review was to examine the clinical process in
      psychiatry, with special reference to clinimetrics, a domain concerned with the
      measurement of clinical phenomena that do not find room in customary taxonomy.
      DATA SOURCES: A MEDLINE search from inception to August 2010 was performed for
      English-language articles using the keywords clinical judgment, clinimetric,
      staging, comorbidity, sequential treatment, and subclinical symptoms in relation
      to psychiatric illness. It was supplemented by a manual search of the literature.
      STUDY SELECTION: Choice of assessment strategies was based on their established
      or potential incremental increase in clinical information compared to use of
      diagnostic criteria. DATA EXTRACTION: Contributions were evaluated according to
      the principles of clinimetrics. RESULTS: Several innovative assessment strategies
      were identified: the use of diagnostic transfer stations with repeated
      assessments instead of diagnostic endpoints, subtyping versus integration of
      different diagnostic categories, staging methods, and broadening of clinical
      information through macroanalysis and microanalysis. The most representative
      examples were selected. CONCLUSIONS: Current assessment strategies in psychiatric
      research do not reflect the sophisticated thinking that underlies clinical
      decisions in practice. The clinimetric perspective provides an intellectual home
      for the reproduction and standardization of these clinical intuitions.

PMID- 21903023
TI  - Decreased nocturnal oxytocin levels in anorexia nervosa are associated with low
      bone mineral density and fat mass.
AB  - OBJECTIVE: Anorexia nervosa is characterized by self-induced starvation and
      associated with severe bone and fat loss. Oxytocin is a peptide hormone involved
      in appetite and energy homeostasis. Recent data show that oxytocin has an
      anabolic effect on bone and stimulates osteoblast function. There is limited
      information about oxytocin levels or their relationship to decreased bone mineral
      density in anorexia nervosa. Our objective was to investigate the relationship
      between oxytocin levels, bone mineral density, and body composition in women with
      anorexia nervosa. METHOD: We studied 36 women, mean +/- SEM age 27.6 +/- 1.3
      years: 17 with DSM-IV anorexia nervosa and 19 healthy controls in a cross
      sectional study. Oxytocin levels were determined from pooled serum samples
      obtained every 20 minutes from 8 pm to 8 am during an inpatient overnight visit.
      Fasting leptin levels were measured. Bone mineral density at the anterior
      posterior and lateral spine and hip and body composition were assessed by dual
      energy x-ray absorptiometry. The study was conducted from September 2004 to June
      2008. RESULTS: Subjects with anorexia nervosa versus healthy controls had lower
      mean +/- SEM oxytocin levels (14.3 +/- 1.5 vs 31.8 +/- 5.1 pg/mL, P = .003),
      leptin levels (2.7 +/- 0.5 vs 11.4 +/- 1.1 ng/mL, P < .0001), bone mineral
      density (anterior-posterior spine: 0.83 +/- 0.02 vs 1.04 +/- 0.03; lateral spine:
      0.63 +/- 0.02 vs 0.81 +/- 0.02; total hip: 0.79 +/- 0.03 vs 0.97 +/- 0.03 g/cm2,
      P < .0001), and fat mass (8.8 +/- 0.6 vs 19.7 +/- 0.9 kg, P < .0001). Oxytocin
      levels were associated with bone mineral density at the anterior-posterior (r =
      0.40, P = .02) and lateral (r = 0.36, P = .04) spine, fat mass (r = 0.42, P =
      .01), and leptin levels (r = 0.55, P = .001). CONCLUSIONS: Overnight secretion of
      oxytocin in women with anorexia nervosa is decreased compared with healthy women.
      Low oxytocin levels are associated with decreased bone mineral density and body
      fat and may contribute to anorexia nervosa-induced bone loss.

PMID- 21903025
TI  - Omega-3 for bipolar disorder: meta-analyses of use in mania and bipolar
      depression.
AB  - OBJECTIVE: Studies using augmentation of pharmacotherapies with omega-3 in
      bipolar disorder have been conducted; however, to date a specific meta-analysis
      in this area has not been published. Thus, we present the significant findings
      from meta-analyses of omega-3 in the treatment of bipolar depression and bipolar
      mania. DATA SOURCES: PubMed, CINAHL, Web of Science, and Cochrane Library
      databases were searched for clinical trials up to September 1, 2010, using the
      search terms bipolar disorder OR bipolar depression OR bipolar mania OR mania OR
      hypomania OR cyclothymia with the search terms omega 3 OR essential fatty acids
      OR polyunsaturated fatty acids OR DHA OR EPA OR fish oil OR flax oil. Clinical
      trial registries and gray literature (published or unpublished data not readily
      accessible via main databases) were also searched. DATA SELECTION: The analysis
      included randomized controlled studies 4 weeks or longer, with a sample size >
      10, written in English, using omega-3 for diagnosed bipolar depression or mania.
      No criteria were set for age, gender, or ethnicity. DATA EXTRACTION: A random
      effects model was used. The model analyzed the standard mean difference between
      treatment and placebo between baseline and endpoint, combining the effect size
      (Hedges g) data. Funnel plot and heterogeneity analyses (I2) were also performed.
      DATA SYNTHESIS: The findings of 5 pooled datasets (n = 291) on the outcome of
      bipolar depression revealed a significant effect in favor of omega-3 (P = .029),
      with a moderate effect size of 0.34. On the outcome of mania, 5 pooled datasets
      (n = 291) revealed a nonsignificant effect in favor of omega-3 (P = .099), with
      an effect size of 0.20. Minor heterogeneity between studies on the outcome of
      bipolar depression was found (I2 = 30%; P = .213), which was not present on the
      outcome of bipolar mania (I2 = 0%; P = .98). Funnel plot symmetry suggested no
      significant likelihood of publication bias. Meta-regression analysis between
      sample size and effect size, however, revealed that studies with smaller sample
      sizes had larger effect sizes (P = .05). CONCLUSIONS: The meta-analytic findings
      provide strong evidence that bipolar depressive symptoms may be improved by
      adjunctive use of omega-3. The evidence, however, does not support its adjunctive
      use in attenuating mania.

PMID- 21903026
TI  - Predictors of psychiatric inpatient suicide: a national prospective register
      based study.
AB  - OBJECTIVE: To study the incidence and risk factors of psychiatric inpatient
      suicide within a national cohort representing all psychiatric hospital
      admissions. METHOD: This national prospective register-based study followed all
      psychiatric hospital admissions in Denmark from the date of patient admission
      until patient discharge or inpatient suicide over a 10-year study period from
      1997 through 2006. By using survival analysis techniques, this study was the
      first to take the inpatient time at risk into account in the estimation of the
      suicide rate and the predictors of suicide among hospital-admitted psychiatric
      patients. RESULTS: Among 126,382 psychiatric inpatients aged 14 years or older,
      279 suicides occurred. The risk of inpatient suicide was high: 860 suicides per
      100,000 inpatient years. Of those individuals who completed suicide, 50% died
      within 18 days of admission. The inpatient suicide rate significantly decreased,
      about 6% each year (HR = 0.94; 95% CI, 0.90-0.99), over this 10-year period.
      Several significant predictors of suicide were found, including the following:
      Patients with a bachelor's degree had a significantly higher hazard ratio (HR) of
      suicide compared with those with a primary school education (HR = 0.41; 95% CI,
      0.29-0.60) or those with vocational training (HR = 0.54; 95% CI, 0.39-0.77).
      Having a personality disorder as a secondary diagnosis (all psychiatric diagnoses
      were made according to ICD-10) raised the risk of suicide (HR = 1.60; 95% CI,
      1.01-2.53), as did having recent contact (within the last year) with a private
      psychologist (HR = 1.85; 95% CI, 1.05-3.28). Recent suicide attempt before
      admission to the hospital was associated with the highest risk of inpatient
      suicide (HR = 4.99; 95% CI, 3.57-6.96). CONCLUSIONS: This study demonstrated a
      high risk of psychiatric inpatient suicide in Denmark of 860 per 100,000
      inpatient years and also revealed several significant predictors of psychiatric
      inpatient suicide. Furthermore, the inpatient suicide rate decreased from 1997
      through 2006 in Denmark.

PMID- 21903027
TI  - Obstructive sleep apnea/hypopnea syndrome and poor response to sertraline in
      patients with coronary heart disease.
AB  - OBJECTIVE: Evidence from several clinical trials in patients with coronary heart
      disease suggests that depression that does not respond to treatment is associated
      with a particularly high risk of adverse cardiac outcomes. The purpose of this
      study was to determine whether obstructive sleep apnea/hypopnea syndrome (OSAHS)
      is associated with a poor response to antidepressant medication in patients with
      coronary heart disease. METHOD: This was a secondary analysis of data from a
      randomized, double-blind, placebo-controlled clinical trial of omega-3 fatty-acid
      augmentation of sertraline for depression in patients with coronary heart
      disease. Patients with documented coronary heart disease were recruited between
      May 2005 and December 2008 from cardiology practices in St Louis, Missouri, and
      through cardiac diagnostic laboratories affiliated with Washington University
      School of Medicine, St Louis, Missouri. One hundred five patients (mean age = 58
      years) with coronary heart disease and current major depressive disorder (DSM-IV)
      were randomized to receive sertraline plus either omega-3 or placebo for 10
      weeks. Cyclical heart-rate patterns associated with OSAHS were detected via
      ambulatory electrocardiography prior to treatment. Symptoms of depression were
      measured at baseline and follow-up with the Beck Depression Inventory-II (BDI-II)
      and the 17-item Hamilton Depression Rating Scale (HDRS-17). The primary endpoint
      was the BDI-II score at 10 weeks. RESULTS: Thirty of the 105 patients (29%) were
      classified as having probable moderate to severe OSAHS on the basis of nighttime
      heart-rate patterns. These OSAHS patients had significantly higher scores on both
      the BDI-II (t = -2.78, P = .01) and the HDRS-17 (t = -2.33, P = .02) at follow-up
      as compared to the reference group. Adjustment for baseline depression score,
      treatment arm (omega-3 vs placebo), body mass index, and inflammatory markers did
      not change the results. Patients with OSAHS reported higher item scores at follow
      up on all depressive symptoms measured with the BDI-II compared to those without
      OSAHS. CONCLUSIONS: Obstructive sleep apnea/hypopnea syndrome is associated with
      a relatively poor response to sertraline treatment for depression. Future
      research should determine the contribution of OSAHS to the increased risk of
      adverse cardiac outcome associated with treatment-resistant depression.

PMID- 21903029
TI  - Suicide deaths of active-duty US military and omega-3 fatty-acid status: a case
      control comparison.
AB  - BACKGROUND: The recent escalation of US military suicide deaths to record numbers
      has been a sentinel for impaired force efficacy and has accelerated the search
      for reversible risk factors. OBJECTIVE: To determine whether deficiencies of
      neuroactive, highly unsaturated omega-3 essential fatty acids (n-3 HUFAs), in
      particular docosahexaenoic acid (DHA), are associated with increased risk of
      suicide death among a large random sample of active-duty US military. METHOD: In
      this retrospective case-control study, serum fatty acids were quantified as a
      percentage of total fatty acids among US military suicide deaths (n = 800) and
      controls (n = 800) matched for age, date of collection of sera, sex, rank, and
      year of incident. Participants were active-duty US military personnel (2002
      2008). For cases, age at death ranged from 17-59 years (mean = 27.3 years, SD =
      7.3 years). Outcome measures included death by suicide, postdeployment health
      assessment questionnaire (Department of Defense Form 2796), and ICD-9 mental
      health diagnosis data. RESULTS: Risk of suicide death was 14% higher per SD of
      lower DHA percentage (OR = 1.14; 95% CI, 1.02-1.27; P < .03) in adjusted logistic
      regressions. Among men, risk of suicide death was 62% greater with low serum DHA
      status (adjusted OR = 1.62; 95% CI, 1.12-2.34; P < .01, comparing DHA below 1.75%
      [n = 1,389] to DHA of 1.75% and above [n = 141]). Risk of suicide death was 52%
      greater in those who reported having seen wounded, dead, or killed coalition
      personnel (OR = 1.52; 95% CI, 1.11-2.09; P < .01). CONCLUSION: This US military
      population had a very low and narrow range of n-3 HUFA status. Although these
      data suggest that low serum DHA may be a risk factor for suicide, well-designed
      intervention trials are needed to evaluate causality.

PMID- 21903030
TI  - Prevalence of mood disorders and service use among US mothers by race and
      ethnicity: results from the National Survey of American Life.
AB  - OBJECTIVE: To describe the rates of mood disorders, the social and demographic
      correlates of mood disorders, and mental health services utilization among
      African American, Caribbean black, and non-Hispanic white mothers. METHOD: Study
      data were collected between February 2001 and June 2003 as part of the National
      Survey of American Life: Coping With Stress in the 21st Century. National
      household probability samples of African Americans and Caribbean blacks were
      surveyed using a slightly modified World Mental Health version of the World
      Health Organization Composite International Diagnostic Interview. Participants
      included 2,019 African American, 799 Caribbean black, and 400 non-Hispanic white
      mothers 18 years and older (N = 3,218). The main outcomes measured were lifetime
      and 12-month diagnoses of DSM-IV mood disorders (major depressive episode,
      dysthymic disorder, bipolar I and II disorders) and mental health services
      utilization. RESULTS: The lifetime prevalence estimate of mood disorders is
      higher for white mothers (21.67%) than for African American mothers (16.77%) and
      Caribbean black mothers (16.42%); however, 12-month mood disorder estimates are
      similar across groups. African American mothers have higher 12-month prevalence
      estimates of bipolar disorder (2.48%) than white mothers (0.59%) and Caribbean
      black mothers (1.16%). African American mothers with higher education levels and
      white mothers who became parents as teenagers are more likely to have a lifetime
      mood disorder. Less than half (45.8%) of black mothers with a past 12-month mood
      disorder diagnosis utilized mental health services. Among black mothers with a 12
      month diagnosis of bipolar disorder, Caribbean blacks utilized mental health
      services at higher rates than African Americans. CONCLUSIONS: Demographic
      correlates for mood disorders varied by race and ethnicity. The findings
      illustrated underutilization of treatment by black mothers, especially African
      American mothers with bipolar disorder.

PMID- 21903031
TI  - Does DSM-IV already capture the dimensional nature of personality disorders?
AB  - OBJECTIVE: Personality disorder research favors a dimensional representation of
      the personality disorders over categorical classification, and this is one of the
      central justifications for changing the diagnostic approach in DSM-5. However,
      recent research has suggested that the most important loss of information in a
      categorical system is the failure to account for subthreshold levels of
      pathology. DSM-IV can be considered to already accommodate a quasi-dimensional
      system insofar as individuals who do not meet the threshold for diagnosis can be
      noted to have traits of the disorder. In the present report, we examined 2
      questions related to dimensional scoring of the personality disorders and the
      association between personality pathology and psychosocial morbidity: (1) Is the
      DSM-IV 3-point dimensional convention (absent, subthreshold traits, present) more
      strongly associated with indicators of psychosocial morbidity than a categorical
      approach toward diagnosis? and (2) How does the 3-point dimensional scoring
      convention compare to the 5-point system proposed for DSM-5 and to a criterion
      count approach in which the dimensional score represents the sum of the number of
      criteria present? METHOD: From September 1997 to June 2008, 2,150 psychiatric
      outpatients were evaluated with semistructured diagnostic interviews for DSM-IV
      Axis I and Axis II disorders and measures of psychosocial morbidity. RESULTS: The
      DSM-IV 3-point dimensional convention was more strongly associated with measures
      of psychosocial morbidity than was categorical diagnosis. There was no difference
      between the 3-point, 5-point, and criterion count methods of scoring the DSM-IV
      personality disorder dimensions. CONCLUSIONS: Dimensional scoring of the DSM-IV
      personality disorders was more highly correlated with measures of psychosocial
      morbidity than was categorical classification. The DSM-IV 3-point rating
      convention was as valid as scoring methods using more finely graded levels of
      severity. These findings argue against changing the current DSM-IV diagnostic
      approach and instead advocate for the increased recognition that DSM-IV already
      includes a valid dimensional rating.

PMID- 21903028
TI  - Retinoic acid and affective disorders: the evidence for an association.
AB  - OBJECTIVE: Isotretinoin (13-cis-retinoic acid), approved by the US Food and Drug
      Administration for the treatment of acne, carries a black box warning related to
      the risk of depression, suicide, and psychosis. Retinoic acid, the active form of
      vitamin A, regulates gene expression in the brain, and isotretinoin is its 13-cis
      isomer. Retinoids represent a group of compounds derived from vitamin A that
      perform a large variety of functions in many systems, in particular the central
      nervous system, and abnormal retinoid levels can have neurologic effects.
      Although infrequent, proper recognition and treatment of psychiatric side effects
      in acne patients is critical given the risk of death and disability. This article
      reviews the evidence for isotretinoin's relationships with depression and
      suicidality. DATA SOURCES: The PsycINFO, MEDLINE, and PubMed searchable database
      indexes were searched for articles published in the English language from 1960 to
      June 2010 using the key words isotretinoin, retinoids, retinoic acid, depression,
      depressive disorders, and vitamin A. Evidence examined includes (1) case reports;
      (2) temporal association between onset of depression and exposure to the drug;
      (3) challenge-rechallenge cases; (4) class effect (other compounds in the same
      class, like vitamin A, having similar neuropsychiatric effects); (5) dose
      response; and (6) biologically plausible mechanisms. STUDY SELECTION: All
      articles in the literature related to isotretinoin, depression, and suicide were
      reviewed, as well as articles related to class effect, dose response, and
      biologic plausibility. DATA EXTRACTION: Information from individual articles in
      the literature was extracted, including number of episodes of depression,
      suicidality, suicide, psychosis, violence and aggression, past psychiatric
      history, time of onset in relation to isotretinoin usage, medication dosage,
      duration of treatment, and dechallenge and challenge history. RESULTS: The
      literature reviewed is consistent with associations of isotretinoin
      administration with depression and with suicide in a subgroup of vulnerable
      individuals. CONCLUSIONS: The relationship between isotretinoin and depression
      may have implications for a greater understanding of the neurobiology of
      affective disorders.

PMID- 21903032
TI  - Successful pharmacologic treatment of major depressive disorder attenuates
      amygdala activation to negative facial expressions: a functional magnetic
      resonance imaging study.
AB  - OBJECTIVE: Studies of the effects of pharmacotherapy for major depressive
      disorder (MDD) on limbic-subcortical-prefrontal brain networks show variable
      results. We quantified functional changes in the amygdala and the related limbic
      subcortical-prefrontal structures after paroxetine treatment with functional
      magnetic resonance imaging relative to clinical responder status. METHOD: We
      scanned 22 patients with unipolar, DSM-IV-defined MDD (men and women aged 25-55
      years; 17-item Hamilton Depression Rating Scale [HDRS(17)] score > 18) at study
      entry and after 6 (T0) and 12 (T1) weeks of paroxetine treatment. Our paradigm
      contrasted negative (fearful, angry), happy, and neutral faces relative to
      scrambled faces. Twenty-one age-matched (+/- 2.5 y) and sex-matched controls were
      scanned once. Patients received open-label paroxetine 20 mg/d for 6 weeks (T0).
      Nonresponders at T0 were randomly assigned to receive double-blind true dose
      escalation (paroxetine 30-50 mg/d) or placebo dose escalation for another 6 weeks
      (T1). The study was conducted from July 2005 to February 2007. RESULTS: At study
      entry, MDD patients showed increased ventral/limbic and decreased dorsal
      prefrontal activations to negative faces. At T0 and T1, respectively, 5/20 and
      13/20 patients responded to paroxetine. After 12 weeks (at T1), overall amygdala
      activations remained unchanged relative to study entry. However, amygdala
      activations were significantly lower in treatment responders versus nonresponders
      (P = .001). Amygdala activations correlated with HDRS(17) scores (P < .04). Left
      amygdala activation correlated inversely with pregenual anterior cingulate cortex
      activation (P = .001). Dorsal cingulate gyrus and dorsolateral prefrontal
      activations increased after 6 and 12 weeks of treatment, regardless of clinical
      response. CONCLUSIONS: Successful paroxetine treatment decreases amygdala
      activation, presumably by improved frontolimbic control, in line with selective
      serotonin reuptake inhibitor-induced increased functional connectivity between
      the pregenual anterior cingulated cortex, prefrontal cortex, and amygdala.
      Changes in amygdala activation when processing negative faces might serve as an
      indicator for improved frontolimbic control, which is required for clinical
      response. TRIAL REGISTRATION: ISRCTN identifier: ISRCTN44111488.

PMID- 21903033
TI  - Diagnostic consistency of major depression with psychosis across 10 years.
AB  - OBJECTIVE: The present study investigates how consistently DSM-IV major
      depressive disorder (MDD) with psychosis was diagnosed by research consensus
      across 10 years and the association of clinical characteristics with diagnostic
      consistency. METHOD: The sample included 146 participants, part of a larger first
      admission cohort (N = 628) presenting to a psychiatric inpatient facility with
      psychosis, who were diagnosed with psychotic depression at least once across 4
      assessments spanning 10 years (after first admission and at 6-month, 24-month,
      and 10-year follow-ups). The primary outcome of this prospective epidemiologic
      study was retention of the best-estimate consensus diagnosis at each assessment.
      Diagnoses at each assessment were determined from semistructured interviews,
      medical records, and informant reports. The participants were recruited from 1989
      to 1995. RESULTS: Fifty-five of the 146 participants (37.7%) were diagnosed with
      psychotic depression at each available assessment; 13 (8.9%) switched from MDD to
      bipolar disorder, 24 (16.4%) switched from MDD to schizophrenia or
      schizoaffective disorder, and the remaining 54 (37.0%) had other patterns of
      diagnostic change. Only 47 of 80 participants (58.8%) diagnosed with MDD at
      baseline retained a mood disorder diagnosis 10 years later (36 [45.0%] had MDD
      and 11 [13.8%] had bipolar disorder), while 16 of 52 participants (30.8%) who
      ended the study with MDD were initially misdiagnosed. Compared to participants
      who were consistently diagnosed with MDD, those switching from MDD to bipolar
      disorder had better premorbid adjustment, more first-degree relatives with MDD,
      better functioning, and fewer negative symptoms at baseline, whereas those
      shifting to the schizophrenia spectrum had a more insidious onset, longer initial
      hospital stays, worse functioning, and more negative symptoms (all P values <
      .05). CONCLUSIONS: The diagnosis of MDD with psychosis among inpatients showed
      poor long-term consistency. For clinicians, results indicate that the diagnosis
      of MDD with psychosis based on a single assessment should be considered
      provisional.

PMID- 21903035
TI  - Hepatitis A and hepatitis A virus/HIV coinfection in men who have sex with men,
      Warsaw, Poland, September 2008 to September 2009.
AB  - We describe the epidemiology and characteristics of hepatitis A among men who
      have sex with men (MSM)who had been hospitalised due to the infection in Warsaw,
      Poland, from September 2008 to September 2009. A total of 50 men were analysed;
      their median age was 28 years (range: 17-43). None had travelled to hepatitis A
      endemic regions during the six months before hospitalisation nor had they been
      vaccinated against hepatitis A. Of the 50 men, 40 had been tested before
      hospitalisation or on admission for the presence of anti-HIV antibodies: six were
      coinfected with HIV.The six HIV-positive MSM were significantly older than those
      who were HIV negative - median age: 37 years(range: 26-43) versus 28 years
      (range: 17-43); p=0.02.No difference in disease severity or the duration of
      hospitalisation was observed, however, between the two groups. Our study
      underlines the need to screen MSM for hepatitis A and to vaccinate them against
      hepatitis A. Given the ages of the MSM in our study,we recommend that this be
      carried out in Poland when the MSM are aged 20-35 years. This should apply not
      only to MSM with multiple casual partners but also to those in monogamous
      relationships.

PMID- 21903036
TI  - Salmonellosis outbreak due to Salmonella enteritidis phage type 14b resistant to
      nalidixic acid, Austria, September 2010.
AB  - We report on a salmonellosis-outbreak due to Salmonella Enteritidis phage type
      14b resistant to nalidixic acid (S. Enteritidis PT14b Nx) among residents and
      employees of a student residence in Austria, September 2010. The outbreak was
      described and analysed by a retrospective cohort study, and microbiological
      environmental investigations were conducted to identify the outbreak source(s)
      and the reservoir of the outbreak strain. A total of 66 persons fulfilled the
      outbreak case definition including 14 laboratory-confirmed cases. Food specific
      cohort-analyses by day revealed that consumption of potato salad (RR: 1.65,
      95%CI: 1.35-2.01, p=0.001) and a cheese-sausage cold plate (RR: 2.24, 95%CI: 1.29
      3.88, p=0.002) on 14 September was associated with being an outbreak case. We
      hypothesised that cross-contamination with S. Enteritidis PT14b Nx positive eggs
      had occurred during preparation of the potato salad and cold plate as a result of
      preparing in parallel egg-containing breaded cutlets on 14 September. A traced
      laying hen holding in eastern Austria was identified as the sole source of the
      consumable eggs in the student residence. By applying the legally mandated
      sampling method for epidemiological-related laying hen farms (one pooled dust
      sample a 150g, two paired boot swabs cultured separately), the outbreak strain
      could not be detected. Our findings, that legally required sampling methods for
      laying hen farms failed to detect the causative pathogen in a laying hen holding,
      despite an epidemiological link, underline the request stated by the European
      Food Safety Authority Panel on Biological Hazards for a more sensitive sampling
      plan in epidemiologically-associated laying hen flocks.

PMID- 21903037
TI  - Ongoing outbreak of West Nile virus infection in humans, Greece, July to August
      2011.
AB  - Between 16 July and 21 August 2011, 31 cases of West Nile neuroinvasive disease
      were reported from four regions in Greece. Of these, 17 occurred in districts
      that had not been affected in 2010. The reoccurrence of human cases in two
      consecutive years (following the large 2010 outbreak) and the spread of the virus
      in new areas suggest that West Nile virus is established in Greece, and its
      transmission may continue to occur in the future.

PMID- 21903040
TI  - Meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia in Tampere
      University Hospital: a case-control study, Finland October 2002 to January 2010.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA) has emerged as a frequent
      pathogen in blood cultures in Pirkanmaa Hospital District (HD), Finland. To study
      risk factors for MRSA bacteraemia and the adequacy of empirical antimicrobial
      treatment, we retrospectively reviewed the hospital records of 102 patients, 51
      with MRSA, and 51 with meticillin-sensitive Staphylococcus aureus (MSSA)
      bacteraemias respectively, who had been admitted to Tampere University Hospital
      in Pirkanmaa HD, from October 2002 to January 2010. For each patient with MRSA
      bacteraemia, one consecutively detected unmatched patient with MSSA bacteraemia
      was chosen as control. Patients with MRSA bacteraemias were significantly older
      (median age: 73 years vs 59 years, p=0.001), were more likely to have been
      transferred directly from another healthcare facility or were already in the
      hospital at the onset of bacteraemia (39/51 vs 26/51, p=0.007) and had a higher
      McCabe class than patients with MSSA bacteraemia (p=0.005). Patients with MRSA
      bacteraemia more seldom received adequate empirical antimicrobial therapy when
      compared to those with MSSA bacteraemia (13/51 vs 43/51, p<0.001). Of previously
      known MRSA carriers 10 of 29 received adequate empirical antimicrobial therapy
      for their condition. The percentage of MRSA bacteraemias among all S. aureus
      bacteraemias in Pirkanmaa HD is high compared to corresponding figures for the
      whole of Finland.

PMID- 21903041
TI  - Surveillance of hospitalised patients with influenza-like illness during pandemic
      influenza A(H1N1) season in Sicily, April 2009-December 2010.
AB  - This paper describes the epidemiology of hospitalised cases with influenza-like
      illness (ILI) and laboratory-confirmed influenza A cases in Sicily (Italy) during
      the 2009 influenza pandemic. The first ILI case diagnosed as infected with
      pandemic influenza A(H1N1)2009 in Sicily was reported in June 2009 and it rapidly
      became the dominant circulating strain. In the period from 30 April 2009 through
      31 December 2010, a total of 2,636 people in Sicily were hospitalised for ILI and
      1,193 were laboratory-confirmed for influenza A. Basic demographic and clinical
      information for all hospitalised patients was collected and population mortality
      rates (PMRs) and case fatality ratios (CFRs) were calculated. The median age of
      hospitalised patients infected with pandemic influenza A(H1N1)2009 was
      significantly lower than that of hospitalised ILI cases in general (18.0 vs. 32.1
      years; p<0.0001). Among adults, women were more susceptible than men. The
      majority of clinical presentations were mild, but 6.6% of hospitalised patients
      required admission to an intensive care unit, of whom 26.3% had confirmed
      influenza A. Twenty-four fatal cases were documented. The age group of 45-54 year
      olds showed the highest PMRs once hospitalised, while CFRs were higher in elderly
      patients of 65 years and older. All fatal cases were confirmed as influenza
      A(H1N1)2009 and most of them had established risk factors for influenza
      complications.

PMID- 21903042
TI  - Ongoing large mumps outbreak in the Federation of Bosnia and Herzegovina, Bosnia
      and Herzegovina, December 2010 to July 2011.
AB  - From December 2010 until the end of July 2011, 5,261 mumps cases were recorded in
      the Federation of Bosnia and Herzegovina, Bosnia and Herzegovina, leading to an
      incidence of 225.8 per 100,000. Fifteen to 19 year-olds (43%) were most affected
      and 62% of cases were male. Mumps-specific IgM antibodies were found in about 70%
      of sera investigated, complications were reported in 41% of 81 hospitalised
      patients. The outbreak affected mainly those unvaccinated or unaware of their
      vaccination status and is probably due to vaccination failures during the war and
      postwar period (1992-1998).

PMID- 21903043
TI  - Plasmodium vivax malaria in a Romanian traveller returning from Greece, August
      2011.
AB  - In August 2011, a Plasmodium vivax malaria infection was diagnosed in a Romanian
      traveller returning from Greece. This case together with several reports over the
      past decade of autochthonous cases in Greece highlight that malaria should be
      considered as differential diagnosis in symptomatic travellers returning from
      this country. Travellers may serve as sentinels of emerging vector-borne
      diseases.

PMID- 21903044
TI  - Comparing imagery and verbal instructions for the experimental modification of
      interpretation and judgmental bias in children.
AB  - BACKGROUND AND OBJECTIVES: Using an interpretation training paradigm, previous
      research has demonstrated that it is possible to modify interpretation biases in
      socially anxious children and that trained interpretation bias affects important
      aspects of social anxiety (Vassilopoulos, Banerjee, & Prantzalou, 2009). The
      current experiment was designed to replicate and extend the results reported by
      Vassilopoulos et al. (2009). METHODS: In a benign interpretation training
      paradigm, descriptions of ambiguous hypothetical events were presented in a form
      requiring participants to endorse the more benign of two interpretations. Ninety
      four primary school children aged between 10 and 12 years were asked to either
      imagine these hypothetical events or to read the same descriptions while thinking
      about their verbal meaning. RESULTS: Participants in the verbal instructions
      condition showed greater decreases in negative interpretations and negative
      emotional consequences of ambiguous events from pre-training to post-training
      than did those in the imagery instructions condition. Additionally, children in
      the verbal instructions condition reported a significant decrease in trait social
      anxiety as well as in their self-reported tendency to discount positive
      information compared with children in the imagery instructions condition.
      LIMITATIONS: The results should be considered in the light of the exclusive use
      of self-report measures and the small effect sizes observed in some analyses.
      CONCLUSIONS: These findings suggest that interpretation training in children can
      be effective with verbal instructions and highlight the need for further
      investigation of how to optimize the effectiveness of interpretation training in
      children.

PMID- 21903045
TI  - Biased number perception of schematic expressions in abstinent heroin abusers
      compared to normal controls.
AB  - BACKGROUND AND OBJECTIVES: Drug-dependent people exhibit biases when evaluating
      discrete emotional facial expressions. Little is known about how drug abusers
      process multiple expressions presented simultaneously. The present study
      investigated the number perception of schematic emotional expressions by
      abstinent heroin abusers. METHODS: Eighty-four heroin abstainers with varied
      lengths of abstinence (short-term, mid-term, and long-term) and twenty healthy
      controls were examined. A method of limits was deployed to obtain estimates
      (points of subjective equality) of perceived numbers of schematic faces
      (expressing positive, neutral, or negative emotion). RESULTS: Major results
      include the following: 1) heroin-abstinent participants showed significantly
      lower points of subjective equality for negative and neutral faces, but not for
      positive faces, compared to control participants; 2) heroin-abstinent
      participants showed lower points of subjective equality for negative faces and
      higher ones for positive faces when compared to neutral faces, while no such
      differences were found in control participants. CONCLUSION: Heroin abusers
      demonstrate an exaggerated perception of number when exposed to negative
      expressions, even after a period of abstinence as long as 10 months. In addition,
      the current results could also reflect an underestimated perception of number
      during exposure to positive expressions and a heightened baseline for neutral
      expressions, or the attribution of negative valence to neutral expressions by
      heroin abusers.

PMID- 21903046
TI  - In vitro modulation of intracellular receptor signaling and cytotoxicity induced
      by extracts of cyanobacteria, complex water blooms and their fractions.
AB  - The biological activity of cyanobacteria and their chemical components have been
      widely studied due to their blooms in eutrophic waters worldwide. The primary
      goal of this study was to determine if individual cyanobacterial species and
      mixtures of cyanobacteria collected from the environment contain compounds with
      the potential for interaction with signaling pathways of the aryl hydrocarbon
      receptor (AhR), androgen receptor (AR), estrogen receptor (ER), glucocorticoid
      receptor (GR) and retinoid acid receptor (RAR). Cytotoxicity and specific toxic
      potencies of products of freshwater cyanobacteria were determined by use of in
      vitro reporter gene trans-activation assays. The testing included samples
      prepared from five selected single cyanobacterial species cultivated in
      laboratory and five complex cyanobacterial biomasses collected from blooms in
      surface waters in the Czech Republic. The results demonstrate estrogenic
      potencies of extracts of cyanobacterial biomasses. Among the laboratory single
      species, the extract of Planktothrix agardhii (intracellular metabolites) had a
      potency of estrogenic equivalents (EEQ) of 3.8 ng 17beta-estradiol/g dw. The
      estimates of EEQs of samples prepared from complex cyanobacterial biomasses
      collected from freshwaters in the Czech Republic ranged from 19 to 2200 ng 17beta
      estradiol/g dw. Several samples prepared from the environmental cyanobacterial
      biomasses potentiated the androgenic potency of dihydrotestosterone. There was no
      dioxin-like, glucocorticoid or anti/retinoic activity observed for any of the
      extracts studied. Extracts of natural complex cyanobacterial biomasses exhibited
      greater and more frequent presence of compounds with specific modes of action,
      mainly estrogenic, and also greater cytotoxicity than extracts of single
      cyanobacterial species. The demonstrated estrogenic potency of the compounds
      present in complex cyanobacterial biomasses is of environmental relevance, and
      could potentially contribute to endocrine disruptive effects in aquatic
      ecosystems in case of great bloom densities.

PMID- 21903047
TI  - Social psychological theories of disordered eating in college women: review and
      integration.
AB  - Because peer interaction, weight/shape, and self-concept formation are
      particularly salient to college women, the implications of social psychological
      theories may be especially far-reaching during the college years. College women
      may be particularly vulnerable to the effects of social comparison,
      objectification, and uses and gratifications theories, which describe social
      cognitive mechanisms that provide an individual with information regarding her
      own view of her body and how she perceives that others perceive her body. The
      current paper will review and integrate findings related to these three theories
      of disordered eating in college women in an effort to present a more
      comprehensive understanding of the social psychological mechanisms that play a
      role in the development and maintenance of such pathology for this group of young
      women. Limitations of and future directions for research on these theories will
      be discussed, as will their potential integration with other factors that
      contribute to disordered eating and implications for treatment and prevention.

PMID- 21903049
TI  - A "small" defect with malignant effect.

PMID- 21903050
TI  - The year in valvular heart disease.

PMID- 21903051
TI  - Global cardiovascular health: urgent need for an intersectoral approach.
AB  - Cardiovascular disease (CVD) is the leading cause of mortality worldwide, with
      more than 80% of CVD deaths occurring in low- and middle-income countries
      (LMICs). There have been several calls for action to address the global burden of
      CVD, but there remains insufficient investment in and implementation of CVD
      prevention and disease management efforts in LMICs. To catalyze the action needed
      to control global CVD, the Institute of Medicine recently produced a report,
      Promoting Cardiovascular Health in the Developing World: A Critical Challenge to
      Achieve Global Health. This paper presents a commentary of the Institute of
      Medicine's report, focusing specifically on the intersectoral nature of
      intervention approaches required to promote global cardiovascular health. We
      describe 3 primary domains of intervention to control global CVD: 1) policy
      approaches; 2) health communication programs; and 3) healthcare delivery
      interventions. We argue that the intersectoral nature of global CVD interventions
      should ideally occur at 2 levels: first, all 3 domains of intervention must be
      activated and engaged simultaneously, rather than only 1 domain at a time; and
      second, within each domain, a synergistic combination of interventions must be
      implemented. A diversity of public and private sector actors, representing
      multiple sectors such as health, agriculture, urban planning, transportation,
      finance, broadcasting, education, and the food and pharmaceutical industries,
      will be required to collaborate for policies, programs, and interventions to be
      optimally aligned. Improved control of global CVD is eminently possible but
      requires an intersectoral approach involving a diversity of actors and
      stakeholders.

PMID- 21903052
TI  - Functional SYNTAX score for risk assessment in multivessel coronary artery
      disease.
AB  - OBJECTIVES: This study was aimed at investigating whether a fractional flow
      reserve (FFR)-guided SYNTAX score (SS), termed "functional SYNTAX score" (FSS),
      would predict clinical outcome better than the classic SS in patients with
      multivessel coronary artery disease (CAD) undergoing percutaneous coronary
      intervention (PCI). BACKGROUND: The SS is a purely anatomic score based on the
      coronary angiogram and predicts outcome after PCI in patients with multivessel
      CAD. FFR-guided PCI improves outcomes by adding functional information to the
      anatomic information obtained from the angiogram. METHODS: The SS was
      prospectively collected in 497 patients enrolled in the FAME (Fractional Flow
      Reserve versus Angiography for Multivessel Evaluation) study. FSS was determined
      by only counting ischemia-producing lesions (FFR <= 0.80). The ability of each
      score to predict major adverse cardiac events (MACE) at 1 year was compared.
      RESULTS: The 497 patients were divided into tertiles of risk based on the SS.
      After determining the FSS for each patient, 32% moved to a lower-risk group as
      follows. MACE occurred in 9.0%, 11.3%, and 26.7% of patients in the low-, medium
      , and high-FSS groups, respectively (p < 0.001). Only FSS and procedure time were
      independent predictors of 1-year MACE. FSS demonstrated a better predictive
      accuracy for MACE compared with SS (Harrell's C of FSS, 0.677 vs. SS, 0.630, p =
      0.02; integrated discrimination improvement of 1.94%, p < 0.001). CONCLUSIONS:
      Recalculating SS by only incorporating ischemia-producing lesions as determined
      by FFR decreases the number of higher-risk patients and better discriminates risk
      for adverse events in patients with multivessel CAD undergoing PCI.

PMID- 21903053
TI  - Bringing it all together: integration of physiology with anatomy during cardiac
      catheterization.

PMID- 21903055
TI  - Hostility and cardiovascular disease.

PMID- 21903054
TI  - Observed hostility and the risk of incident ischemic heart disease: a prospective
      population study from the 1995 Canadian Nova Scotia Health Survey.
AB  - OBJECTIVES: The aim of this study was to examine the relation between hostility
      and incident ischemic heart disease (IHD) and to determine whether observed
      hostility is superior to patient-reported hostility for the prediction of IHD in
      a large, prospective observational study. BACKGROUND: Some studies have found
      that hostile patients have an increased risk of incident IHD. However, no studies
      have compared methods of hostility assessment or considered important
      psychosocial and cardiovascular risk factors as confounders. Furthermore, it is
      unknown whether all expressions of hostility carry equal risk or whether certain
      manifestations are more cardiotoxic. METHODS: We assessed the independent
      relationship between baseline observed hostility and 10-year incident IHD in
      1,749 adults of the population-based Canadian Nova Scotia Health Survey. RESULTS:
      There were 149 (8.5%) incident IHD events (140 nonfatal, 9 fatal) during the
      15,295 person-years of observation (9.74 events/1,000 person-years). Participants
      with any observed hostility had a greater risk of incident IHD than those without
      (p = 0.02); no such relation was found for patient-reported hostility. Those with
      any observed hostility had a significantly greater risk of incident IHD (hazard
      ratio: 2.06, 95% confidence interval: 1.04 to 4.08, p = 0.04), after adjusting
      for cardiovascular (age, sex, Framingham Risk Score) and psychosocial
      (depression, positive affect, patient-reported hostility, and anger) risk
      factors. CONCLUSIONS: The presence of any observed hostility at baseline was
      associated with a 2-fold increased risk of incident IHD over 10 years of follow
      up. Compared with patient-reported measures, observed hostility is a superior
      predictor of IHD.

PMID- 21903056
TI  - Enhanced Rho-kinase activity in circulating neutrophils of patients with
      vasospastic angina: a possible biomarker for diagnosis and disease activity
      assessment.
AB  - OBJECTIVES: The aim of this study was to examine whether Rho-kinase activity is
      systemically enhanced in patients with vasospastic angina (VSA) and, if so,
      whether a noninvasive diagnostic method could be developed to improve practice.
      BACKGROUND: The activated Rho-kinase pathway plays a central role in the
      molecular mechanism of coronary vasospasm in animal models and patients with VSA.
      Recently, it has been reported that Rho-kinase activity in circulating leukocytes
      is associated with various diseases. METHODS: Fifty-three consecutive patients
      with chest pain who underwent acetylcholine provocation testing for coronary
      spasm were examined. Patients were divided into 2 groups depending on their
      response to the test: VSA (n = 33) and non-VSA (n = 20) groups. Venous blood
      samples were collected to measure Rho-kinase activity in circulating neutrophils,
      determined by the extent of phosphorylation of myosin-binding subunit (MBS), a
      substrate of Rho-kinase. RESULTS: Rho-kinase activity was significantly higher in
      the VSA group than in the non-VSA group (phosphorylated MBS/total MBS ratio 1.33
      +/- 0.37 vs. 0.95 +/- 0.22, p < 0.001). In the VSA group, no correlation was
      noted between Rho-kinase activity and high-sensitivity C-reactive protein,
      smoking, or accumulated number of coronary risk factors. After the 3-month
      medical treatment, Rho-kinase activity in the VSA group was significantly
      decreased to 1.08 +/- 0.31 (p < 0.001). On receiver-operating characteristic
      curve analysis, a phosphorylated MBS ratio of 1.18 was identified as the best
      cutoff level to predict the diagnosis of VSA. CONCLUSIONS: These results indicate
      that Rho-kinase activity in circulating neutrophils is enhanced in patients with
      VSA and may be a useful biomarker for diagnosis and disease activity assessment
      of the vasospastic disorder.

PMID- 21903057
TI  - New light on a forgotten disease: vasospastic angina.

PMID- 21903059
TI  - Iron metabolism, anemia, and heart failure.

PMID- 21903058
TI  - Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and
      relation to anemia, exercise capacity, and survival.
AB  - OBJECTIVES: The aim of this study was to comprehensively delineate iron
      metabolism and its implications in patients with chronic heart failure (CHF).
      BACKGROUND: Iron deficiency is an emerging therapeutic target in CHF. METHODS:
      Iron and clinical indexes were quantified in 157 patients with CHF. RESULTS:
      Several observations were made. First, iron homeostasis was deranged in anemic
      and nonanemic subjects and characterized by diminished circulating (transferrin
      saturation) and functional (mean cell hemoglobin concentration) iron status in
      the face of seemingly adequate stores (ferritin). Second, while iron overload and
      elevated iron stores were rare (1%), iron deficiency (transferrin saturation
      <20%) was evident in 43% of patients. Third, disordered iron homeostasis related
      closely to worsening inflammation and disease severity and strongly predicted
      lower hemoglobin levels independently of age, sex, erythrocyte sedimentation
      rate, New York Heart Association (NYHA) functional class, and creatinine. Fourth,
      the etiologies of anemia varied with disease severity, with an iron-deficient
      substrate (anemia of chronic disease and/or iron-deficiency anemia) evident in
      16%, 72%, and 100% of anemic NYHA functional class I or II, III, and IV patients,
      respectively. Although anemia of chronic disease was more prevalent than iron
      deficiency anemia, both conditions coexisted in 17% of subjects. Fifth, iron
      deficiency was associated with lower peak oxygen consumption and higher ratios of
      ventilation to carbon dioxide production and identified those at enhanced risk
      for death (hazard ratio: 3.38; 95% confidence interval: 1.48 to 7.72; p = 0.004)
      independently of hemoglobin. Nonanemic iron-deficient patients had a 2-fold
      greater risk for death than anemic iron-replete subjects. CONCLUSIONS: Disordered
      iron homeostasis in patients with CHF relates to impaired exercise capacity and
      survival and appears prognostically more ominous than anemia.

PMID- 21903060
TI  - Sudden death in young adults: an autopsy-based series of a population undergoing
      active surveillance.
AB  - OBJECTIVES: The purpose of this study was to define the incidence and
      characterization of cardiovascular cause of sudden death in the young.
      BACKGROUND: The epidemiology of sudden cardiac death (SCD) in young adults is
      based on small studies and uncontrolled observations. Identifying causes of
      sudden death in this population is important for guiding approaches to
      prevention. METHODS: We performed a retrospective cohort study using demographic
      and autopsy data from the Department of Defense Cardiovascular Death Registry
      over a 10-year period comprising 15.2 million person-years of active
      surveillance. RESULTS: We reviewed all nontraumatic sudden deaths in persons 18
      years of age and over. We identified 902 subjects in whom the adjudicated cause
      of death was of potential cardiac etiology, with a mean age of 38 +/- 11 years.
      The mortality rate for SCD per 100,000 person-years for the study period was 6.7
      for males and 1.4 for females (p < 0.0001). Sudden death was attributed to a
      cardiac condition in 715 (79.3%) and was unexplained in 187 (20.7%). The
      incidence of sudden unexplained death (SUD) was 1.2 per 100,000 person-years for
      persons <35 years of age, and 2.0 per 100,000 person-years for those >= 35 years
      of age (p < 0.001). The incidence of fatal atherosclerotic coronary artery
      disease was 0.7 per 100,000 person-years for those <35 years of age, and 13.7 per
      100,000 person-years for those >= 35 years of age (p < 0.001). CONCLUSIONS:
      Prevention of sudden death in the young adult should focus on evaluation for
      causes known to be associated with SUD (e.g., primary arrhythmia) among persons
      <35 years of age, with an emphasis on atherosclerotic coronary disease in those
      >= 35 years of age.

PMID- 21903061
TI  - Age-related changes in aortic arch geometry: relationship with proximal aortic
      function and left ventricular mass and remodeling.
AB  - OBJECTIVES: We sought to define age-related geometric changes of the aortic arch
      and determine their relationship to central aortic stiffness and left ventricular
      (LV) remodeling. BACKGROUND: The proximal aorta has been shown to thicken,
      enlarge in diameter, and lengthen with aging in humans. However, no systematic
      study has described age-related longitudinal and transversal remodeling of the
      aortic arch and their relationship with LV mass and remodeling. METHODS: We
      studied 100 subjects (55 women, 45 men, average age 46 +/- 16 years) free of
      overt cardiovascular disease using magnetic resonance imaging to determine aortic
      arch geometry (length, diameters, height, width, and curvature), aortic arch
      function (local aortic distensibility and arch pulse wave velocity [PWV]), and LV
      volumes and mass. Radial tonometry was used to calculate central blood pressure.
      RESULTS: Aortic diameters and arch length increased significantly with age. The
      ascending aorta length increased most, with age leading to aortic arch widening
      and decreased curvature. These geometric changes of the aortic arch were
      significantly related to decreased ascending aortic distensibility, increased
      aortic arch PWV (p < 0.001), and increased central blood pressures (p < 0.001).
      Increased ascending aortic diameter, lengthening, and decreased curvature of the
      aortic arch (unfolding) were all significantly associated with increased LV mass
      and concentric remodeling independently of age, sex, body size, and central blood
      pressure (p < 0.01). CONCLUSIONS: Age-related unfolding of the aortic arch is
      related to increased proximal aortic stiffness in individuals without
      cardiovascular disease and associated with increased LV mass and mass-to-volume
      ratio independent of age, body size, central pressure, and cardiovascular risk
      factors.

PMID- 21903062
TI  - Midwall fibrosis is an independent predictor of mortality in patients with aortic
      stenosis.
AB  - OBJECTIVES: The goal of this study was to assess the prognostic significance of
      midwall and infarct patterns of late gadolinium enhancement (LGE) in aortic
      stenosis. BACKGROUND: Myocardial fibrosis occurs in aortic stenosis as part of
      the hypertrophic response. It can be detected by LGE, which is associated with an
      adverse prognosis in a range of other cardiac conditions. METHODS: Between
      January 2003 and October 2008, consecutive patients with moderate or severe
      aortic stenosis undergoing cardiovascular magnetic resonance with administration
      of gadolinium contrast were enrolled into a registry. Patients were categorized
      into absent, midwall, or infarct patterns of LGE by blinded independent
      observers. Patient follow-up was completed using patient questionnaires, source
      record data, and the National Strategic Tracing Service. RESULTS: A total of 143
      patients (age 68 +/- 14 years; 97 male) were followed up for 2.0 +/- 1.4 years.
      Seventy-two underwent aortic valve replacement, and 27 died (24 cardiac, 3 sudden
      cardiac deaths). Compared with those with no LGE (n = 49), univariate analysis
      revealed that patients with midwall fibrosis (n = 54) had an 8-fold increase in
      all-cause mortality despite similar aortic stenosis severity and coronary artery
      disease burden. Patients with an infarct pattern (n = 40) had a 6-fold increase.
      Midwall fibrosis (hazard ratio: 5.35; 95% confidence interval: 1.16 to 24.56; p =
      0.03) and ejection fraction (hazard ratio: 0.96; 95% confidence interval: 0.94 to
      0.99; p = 0.01) were independent predictors of all-cause mortality by
      multivariate analysis. CONCLUSIONS: Midwall fibrosis was an independent predictor
      of mortality in patients with moderate and severe aortic stenosis. It has
      incremental prognostic value to ejection fraction and may provide a useful method
      of risk stratification.

PMID- 21903063
TI  - Is ventricular arrhythmia a possible mediator of the association between aortic
      stenosis-related midwall fibrosis and mortality?

PMID- 21903064
TI  - Successful placement of left atrial appendage closure device is heavily dependent
      on 3-dimensional transesophageal imaging.

PMID- 21903066
TI  - Is cardiorespiratory fitness a unique cardiovascular disease risk factor?

PMID- 21903068
TI  - Sex-specific outcomes for HeartMate II.

PMID- 21903069
TI  - DEG/ENaCs lead by a nose: mechanotransduction in a polymodal sensory neuron.
AB  - Degenerin/epithelial sodium channels (DEG/ENaCs) are luminaries of gentle touch
      in Caenorhabditis elegans. In this issue of Neuron, Geffeney et al. demonstrate
      that eponymous DEG-1 channels carry mechanotransduction currents in a polymodal
      neuron, where they act upstream of transient receptor potential (TRP) channels.

PMID- 21903070
TI  - Reorganization of striatal inhibitory microcircuits leads to pathological
      synchrony in the Basal Ganglia.
AB  - Neural synchronization plays an important role in information flow in the nervous
      system under healthy and pathological conditions. In this issue of Neuron, Gittis
      et al. show that reorganization of striatal microcircuits promotes synchronous
      activity and may underlie the pathological network oscillations at the root of
      motor symptoms described in Parkinson's disease.

PMID- 21903071
TI  - Life and death decision in adult neurogenesis: in praise of napping.
AB  - Among the thousands of new neurons that integrate into the adult olfactory bulb
      each day, 50% are eliminated through apoptosis. In this issue of Neuron, Yokoyama
      et al. take steps toward deciphering the behavioral contexts that regulate
      newborn cell elimination.

PMID- 21903072
TI  - Dendritic spines and distributed circuits.
AB  - Dendritic spines receive most excitatory connections in pyramidal cells and many
      other principal neurons. But why do neurons use spines, when they could
      accommodate excitatory contacts directly on their dendritic shafts? One
      suggestion is that spines serve to connect with passing axons, thus increasing
      the connectivity of the dendrites. Another hypothesis is that spines are
      biochemical compartments that enable input-specific synaptic plasticity. A third
      possibility is that spines have an electrical role, filtering synaptic potentials
      and electrically isolating inputs from each other. In this review, I argue that,
      when viewed from the perspective of the circuit function, these three functions
      dovetail with one another to achieve a single overarching goal: to implement a
      distributed circuit with widespread connectivity. Spines would endow these
      circuits with nonsaturating, linear integration and input-specific learning
      rules, which would enable them to function as neural networks, with emergent
      encoding and processing of information.

PMID- 21903073
TI  - Role of astrocytes in neurovascular coupling.
AB  - Neural activity is intimately tied to blood flow in the brain. This coupling is
      specific enough in space and time that modern imaging methods use local
      hemodynamics as a measure of brain activity. In this review, we discuss recent
      evidence indicating that neuronal activity is coupled to local blood flow changes
      through an intermediary, the astrocyte. We highlight unresolved issues regarding
      the role of astrocytes and propose ways to address them using novel techniques.
      Our focus is on cellular level analysis in vivo, but we also relate mechanistic
      insights gained from ex vivo experiments to native tissue. We also review some
      strategies to harness advances in optical and genetic methods to study
      neurovascular coupling in the intact brain.

PMID- 21903074
TI  - Development of a method for the purification and culture of rodent astrocytes.
AB  - The inability to purify and culture astrocytes has long hindered studies of their
      function. Whereas astrocyte progenitor cells can be cultured from neonatal brain,
      culture of mature astrocytes from postnatal brain has not been possible. Here, we
      report a new method to prospectively purify astrocytes by immunopanning. These
      astrocytes undergo apoptosis in culture, but vascular cells and HBEGF promote
      their survival in serum-free culture. We found that some developing astrocytes
      normally undergo apoptosis in vivo and that the vast majority of astrocytes
      contact blood vessels, suggesting that astrocytes are matched to blood vessels by
      competing for vascular-derived trophic factors such as HBEGF. Compared to
      traditional astrocyte cultures, the gene profiles of the cultured purified
      postnatal astrocytes much more closely resemble those of in vivo astrocytes.
      Although these astrocytes strongly promote synapse formation and function, they
      do not secrete glutamate in response to stimulation.

PMID- 21903075
TI  - Rapid plasticity of visual responses in the adult lateral geniculate nucleus.
AB  - Compared to the developing visual system, where neuronal plasticity has been well
      characterized at multiple levels, little is known about plasticity in the adult,
      particularly within subcortical structures. We made intraocular injections of 2
      amino-4-phosphonobutyric acid (APB) in adult cats to block visual responses in On
      center retinal ganglion cells and examined the consequences on visual responses
      in the lateral geniculate nucleus (LGN) of the thalamus. In contrast to current
      views of retinogeniculate organization, which hold that On-center LGN neurons
      should become silent with APB, we find that ~50% of On-center neurons rapidly
      develop Off-center responses. The time course of these emergent responses and the
      actions of APB in the retina indicate the plasticity occurs within the LGN. These
      results suggest there is greater divergence of retinogeniculate connections than
      previously recognized and that functionally silent, nonspecific retinal inputs
      can serve as a substrate for rapid plasticity in the adult.

PMID- 21903077
TI  - Nitration of tyrosine 10 critically enhances amyloid beta aggregation and plaque
      formation.
AB  - Part of the inflammatory response in Alzheimer's disease (AD) is the upregulation
      of the inducible nitric oxide synthase (NOS2) resulting in increased NO
      production. NO contributes to cell signaling by inducing posttranslational
      protein modifications. Under pathological conditions there is a shift from the
      signal transducing actions to the formation of protein tyrosine nitration by
      secondary products like peroxynitrite and nitrogen dioxide. We identified amyloid
      beta (Abeta) as an NO target, which is nitrated at tyrosine 10 (3NTyr(10)-Abeta).
      Nitration of Abeta accelerated its aggregation and was detected in the core of
      Abeta plaques of APP/PS1 mice and AD brains. NOS2 deficiency or oral treatment
      with the NOS2 inhibitor L-NIL strongly decreased 3NTyr(10)-Abeta, overall Abeta
      deposition and cognitive dysfunction in APP/PS1 mice. Further, injection of
      3NTyr(10)-Abeta into the brain of young APP/PS1 mice induced beta-amyloidosis.
      This suggests a disease modifying role for NOS2 in AD and therefore represents a
      potential therapeutic target.

PMID- 21903076
TI  - Control of neuronal morphology by the atypical cadherin Fat3.
AB  - Neurons receive signals through dendrites that vary widely in number and
      organization, ranging from one primary dendrite to multiple complex dendritic
      trees. For example, retinal amacrine cells (ACs) project primary dendrites into a
      discrete synaptic layer called the inner plexiform layer (IPL) and only rarely
      extend processes into other retinal layers. Here, we show that the atypical
      cadherin Fat3 ensures that ACs develop this unipolar morphology. AC precursors
      are initially multipolar but lose neurites as they migrate through the
      neuroblastic layer. In fat3 mutants, pruning is unreliable and ACs elaborate two
      dendritic trees: one in the IPL and a second projecting away from the IPL that
      stratifies to form an additional synaptic layer. Since complex nervous systems
      are characterized by the addition of layers, these results demonstrate that
      mutations in a single gene can cause fundamental changes in circuit organization
      that may drive nervous system evolution.

PMID- 21903078
TI  - DEG/ENaC but not TRP channels are the major mechanoelectrical transduction
      channels in a C. elegans nociceptor.
AB  - Many nociceptors detect mechanical cues, but the ion channels responsible for
      mechanotransduction in these sensory neurons remain obscure. Using in vivo
      recordings and genetic dissection, we identified the DEG/ENaC protein, DEG-1, as
      the major mechanotransduction channel in ASH, a polymodal nociceptor in
      Caenorhabditis elegans. But DEG-1 is not the only mechanotransduction channel in
      ASH: loss of deg-1 revealed a minor current whose properties differ from those
      expected of DEG/ENaC channels. This current was independent of two TRPV channels
      expressed in ASH. Although loss of these TRPV channels inhibits behavioral
      responses to noxious stimuli, we found that both mechanoreceptor currents and
      potentials were essentially wild-type in TRPV mutants. We propose that ASH
      nociceptors rely on two genetically distinct mechanotransduction channels and
      that TRPV channels contribute to encoding and transmitting information. Because
      mammalian and insect nociceptors also coexpress DEG/ENaCs and TRPVs, the cellular
      functions elaborated here for these ion channels may be conserved.

PMID- 21903079
TI  - Rapid target-specific remodeling of fast-spiking inhibitory circuits after loss
      of dopamine.
AB  - In Parkinson's disease (PD), dopamine depletion alters neuronal activity in the
      direct and indirect pathways and leads to increased synchrony in the basal
      ganglia network. However, the origins of these changes remain elusive. Because
      GABAergic interneurons regulate activity of projection neurons and promote
      neuronal synchrony, we recorded from pairs of striatal fast-spiking (FS)
      interneurons and direct- or indirect-pathway MSNs after dopamine depletion with 6
      OHDA. Synaptic properties of FS-MSN connections remained similar, yet within 3
      days of dopamine depletion, individual FS cells doubled their connectivity to
      indirect-pathway MSNs, whereas connections to direct-pathway MSNs remained
      unchanged. A model of the striatal microcircuit revealed that such increases in
      FS innervation were effective at enhancing synchrony within targeted cell
      populations. These data suggest that after dopamine depletion, rapid target
      specific microcircuit organization in the striatum may lead to increased
      synchrony of indirect-pathway MSNs that contributes to pathological network
      oscillations and motor symptoms of PD.

PMID- 21903080
TI  - Loss of sensory input causes rapid structural changes of inhibitory neurons in
      adult mouse visual cortex.
AB  - A fundamental property of neuronal circuits is the ability to adapt to altered
      sensory inputs. It is well established that the functional synaptic changes
      underlying this adaptation are reflected by structural modifications in
      excitatory neurons. In contrast, the degree to which structural plasticity in
      inhibitory neurons accompanies functional changes is less clear. Here, we use two
      photon imaging to monitor the fine structure of inhibitory neurons in mouse
      visual cortex after deprivation induced by retinal lesions. We find that a subset
      of inhibitory neurons carry dendritic spines, which form glutamatergic synapses.
      Removal of visual input correlates with a rapid and lasting reduction in the
      number of inhibitory cell spines. Similar to the effects seen for dendritic
      spines, the number of inhibitory neuron boutons dropped sharply after retinal
      lesions. Together, these data suggest that structural changes in inhibitory
      neurons may precede structural changes in excitatory circuitry, which ultimately
      result in functional adaptation following sensory deprivation.

PMID- 21903081
TI  - Elimination of adult-born neurons in the olfactory bulb is promoted during the
      postprandial period.
AB  - Granule cells (GCs) in the mouse olfactory bulb (OB) continue to be generated in
      adulthood, with nearly half incorporated and the remainder eliminated. Here, we
      show that elimination of adult-born GCs is promoted during a short time window in
      the postprandial period. Under restricted feeding, the number of apoptotic GCs
      specifically increased within a few hours after the start of feeding. This
      enhanced GC apoptosis occurred in association with postprandial behaviors that
      included grooming, resting, and sleeping, and was particularly correlated with
      the length of postprandial sleep. Further, deprivation of olfactory sensory
      experience in the local OB area potentiated the extent of GC elimination in that
      area during the postprandial period. Sensory experience-dependent enhancement of
      GC elimination also occurred during postprandial period under natural feeding
      condition. These results suggest that extensive structural reorganization of
      bulbar circuitry occurs during the postprandial period, reflecting sensory
      experience during preceding waking period.

PMID- 21903082
TI  - Single units in the medial prefrontal cortex with anxiety-related firing patterns
      are preferentially influenced by ventral hippocampal activity.
AB  - The medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC) functionally
      interact during innate anxiety tasks. To explore the consequences of this
      interaction, we examined task-related firing of single units from the mPFC of
      mice exploring standard and modified versions of the elevated plus maze (EPM), an
      innate anxiety paradigm. Hippocampal local field potentials (LFPs) were
      simultaneously monitored. The population of mPFC units distinguished between safe
      and aversive locations within the maze, regardless of the nature of the
      anxiogenic stimulus. Strikingly, mPFC units with stronger task-related activity
      were more strongly coupled to theta-frequency activity in the vHPC LFP. Lastly,
      task-related activity was inversely correlated with behavioral measures of
      anxiety. These results clarify the role of the vHPC-mPFC circuit in innate
      anxiety and underscore how specific inputs may be involved in the generation of
      behaviorally relevant neural activity within the mPFC.

PMID- 21903083
TI  - The sound of silence: ionic mechanisms encoding sound termination.
AB  - Offset responses upon termination of a stimulus are crucial for perceptual
      grouping and gap detection. These gaps are key features of vocal communication,
      but an ionic mechanism capable of generating fast offsets from auditory stimuli
      has proven elusive. Offset firing arises in the brainstem superior paraolivary
      nucleus (SPN), which receives powerful inhibition during sound and converts this
      into precise action potential (AP) firing upon sound termination. Whole-cell
      patch recording in vitro showed that offset firing was triggered by IPSPs rather
      than EPSPs. We show that AP firing can emerge from inhibition through integration
      of large IPSPs, driven by an extremely negative chloride reversal potential
      (E(Cl)), combined with a large hyperpolarization-activated nonspecific cationic
      current (I(H)), with a secondary contribution from a T-type calcium conductance
      (I(TCa)). On activation by the IPSP, I(H) potently accelerates the membrane time
      constant, so when the sound ceases, a rapid repolarization triggers multiple
      offset APs that match onset timing accuracy.

PMID- 21903084
TI  - Sound texture perception via statistics of the auditory periphery: evidence from
      sound synthesis.
AB  - Rainstorms, insect swarms, and galloping horses produce "sound textures"--the
      collective result of many similar acoustic events. Sound textures are
      distinguished by temporal homogeneity, suggesting they could be recognized with
      time-averaged statistics. To test this hypothesis, we processed real-world
      textures with an auditory model containing filters tuned for sound frequencies
      and their modulations, and measured statistics of the resulting decomposition. We
      then assessed the realism and recognizability of novel sounds synthesized to have
      matching statistics. Statistics of individual frequency channels, capturing
      spectral power and sparsity, generally failed to produce compelling synthetic
      textures; however, combining them with correlations between channels produced
      identifiable and natural-sounding textures. Synthesis quality declined if
      statistics were computed from biologically implausible auditory models. The
      results suggest that sound texture perception is mediated by relatively simple
      statistics of early auditory representations, presumably computed by downstream
      neural populations. The synthesis methodology offers a powerful tool for their
      further investigation.

PMID- 21903086
TI  - The challenge of sustaining and accelerating clinical epilepsy research.

PMID- 21903085
TI  - Visual feature-tolerance in the reading network.
AB  - A century of neurology and neuroscience shows that seeing words depends on
      ventral occipital-temporal (VOT) circuitry. Typically, reading is learned using
      high-contrast line-contour words. We explored whether a specific VOT region, the
      visual word form area (VWFA), learns to see only these words or recognizes words
      independent of the specific shape-defining visual features. Word forms were
      created using atypical features (motion-dots, luminance-dots) whose statistical
      properties control word-visibility. We measured fMRI responses as word form
      visibility varied, and we used TMS to interfere with neural processing in
      specific cortical circuits, while subjects performed a lexical decision task. For
      all features, VWFA responses increased with word-visibility and correlated with
      performance. TMS applied to motion-specialized area hMT+ disrupted reading
      performance for motion-dots, but not line-contours or luminance-dots. A
      quantitative model describes feature-convergence in the VWFA and relates VWFA
      responses to behavioral performance. These findings suggest how visual feature
      tolerance in the reading network arises through signal convergence from feature
      specialized cortical areas.

PMID- 21903087
TI  - Do you know it when you see it? Tips for recognizing good studies in medical
      education.

PMID- 21903088
TI  - Pediatric mental health services: complex problems demand comprehensive
      solutions.

PMID- 21903089
TI  - Statement of principles: APA-industry relationship.

PMID- 21903090
TI  - The heme uptake process in Trypanosoma cruzi epimastigotes is inhibited by heme
      analogues and by inhibitors of ABC transporters.
AB  - Heme (iron protoporphyrin IX) is an important molecule involved in many
      biological reactions, including oxygen transport, respiration, photosynthesis and
      drug detoxification. Trypanosoma cruzi parasites, the etiological agent of
      Chagas' disease, take up heme from the environment to supply their nutritional
      needs because they do not synthesize this cofactor. However, the mechanisms
      involved in heme transport across biological membranes are poorly understood.
      Indeed, in T. cruzi, no heme transporter has yet been characterized. In the
      present work, we evaluate the heme uptake processes by T. cruzi epimastigotes
      using fluorescent heme-analogues. Heme uptake decreased significantly when cells
      were pretreated with different concentrations of SnPPIX, PdMPIX or ZnMPIX, this
      observed competition suggests that they are taken up by the same transport
      system. We studied the growth behavior of epimastigotes using the same heme
      analogues and the treatments with SnPPIX or PdMPIX impaired cell growth but when
      heme was added to the culture medium the observed inhibition was partially
      reversed. In addition, we tested how the heme uptake processes are affected by
      the presence of different transporter inhibitors. When the cells were treated
      with inhibitors and then incubated with heme, heme uptake decreased significantly
      for all treatments. These results constitute a strong indication for the
      existence of a protein associated with porphyrin transport in T. cruzi, possibly
      ATP-binding cassette transporters (ABC-transporter).

PMID- 21903091
TI  - Mesenchymal stem cell marker Stro-1 is a 75 kd endothelial antigen.
AB  - Stro-1 is the best-known mesenchymal stem cell (MSC) marker. However, previous
      studies have observed its expression in the endothelium. In the present study we
      performed immunofluorescence (IF) staining for Stro-1, using endothelial marker
      vWF as reference. In the liver, both proteins were expressed in the endothelium
      of the central veins and hepatic sinusoids. In the lung, both were expressed in
      the endothelium of pulmonary blood vessels, but while vWF was absent in the
      alveolar capillaries, Stro-1 was present. In the kidney, both were expressed in
      the endothelium of renal arterial branches, but while vWF was strongly expressed
      in the glomeruli, Stro-1 only scantly. IF staining in cultured endothelial cells
      also showed extensive overlaps between Stro-1 and vWF. Western blot analysis with
      Stro-1 antibody detected a single protein band of 75 kd in endothelial cells but
      not smooth muscle cells, fibroblasts, or B cells. Cancer cell lines PC3, DU145,
      MCF7, and K562 were also positive. Adipose-derived stem cells (ADSCs) expressed
      higher levels of Stro-1 when cultured beyond the first passage or when induced to
      differentiate into endothelial cells. These data, together with previous studies,
      indicate that Stro-1 is intrinsically an endothelial antigen, and its expression
      in MSC is probably an induced event.

PMID- 21903092
TI  - Silencing of the SNARE protein NAPA sensitizes cancer cells to cisplatin by
      inducing ERK1/2 signaling, synoviolin ubiquitination and p53 accumulation.
AB  - We found earlier that NAPA represents an anti-apoptotic protein that promotes
      resistance to cisplatin in cancer cells by inducing the degradation of the tumor
      suppressor p53. In the present study, we investigated the cellular mechanism
      underlying the degradation of p53 by NAPA. Knockdown of NAPA using short-hairpin
      RNA was shown to induce p53 accumulation and to sensitize HEK293 cells to
      cisplatin. On the other hand, this sensitization effect was not found in H1299
      lung carcinoma cells which lack p53. Expression of exogenous p53 in H1299 cells
      was increased following knockdown of NAPA and these cells showed increased
      sensitivity to cisplatin-induced apoptosis. Notably, knockdown of NAPA induced
      the ubiquitination and degradation of the E3 ubiquitin ligase synoviolin and the
      accumulation of p53 in unstressed HEK293 cells. Conversely, NAPA overexpression
      decreased the ubiquitination and degradation of synoviolin, and reduced p53
      protein level. Knockdown of NAPA disrupted the interaction between synoviolin and
      proteins that form the endoplasmic reticulum-associated degradation (ERAD)
      complex and in turn decreased the ability of this complex to ubiquitinate p53. In
      addition, knockdown of NAPA induced the activation of the MAPK kinases ERK, JNK
      and p38, but only inhibition of ERK reduced synoviolin ubiquitination and p53
      accumulation. These results indicate that NAPA promotes resistance to cisplatin
      through synoviolin and the ERAD complex which together induce the degradation of
      p53 and thus prevent apoptosis. Based on these findings, we propose that the
      combination of cisplatin and knockdown of NAPA represents a novel and attractive
      strategy to eradicate p53-sensitive cancer cells.

PMID- 21903093
TI  - Guggulsterone sensitizes hepatoma cells to TRAIL-induced apoptosis through the
      induction of CHOP-dependent DR5: involvement of ROS-dependent ER-stress.
AB  - Guggulsterone (GGS) has anti-tumor and anti-angiogenesis potential by suppressing
      nuclear factor-kappaB and STAT3 activity. Although GGS has been suggested as a
      potential therapeutic agent for treating various cancers, the underlying
      molecular mechanisms are unknown. Therefore, we investigated whether GGS
      sensitizes hepatocellular carcinoma cells (HCC) to apoptosis mediated by tumor
      necrosis factor-related apoptosis inducing ligand (TRAIL). The apoptotic
      mechanism induced by treatment with a GGS/TRAIL combination involved the loss of
      mitochondrial transmembrane potential and consequent activation of caspases. GGS
      also induced upregulation of the death receptor DR5 for TRAIL. The effects seemed
      to be associated with eIF2alpha and CHOP activation, which are related to the
      endoplasmic reticulum (ER) stress response and apoptosis. This relationship was
      suggested by the observation that CHOP downregulation by specific siRNA
      attenuated both GGS-mediated DR5 upregulation and the cytotoxicity induced by
      GGS/TRAIL co-treatment. Moreover, salubrinal, a specific eIF-2alpha
      phosphorylation-inducing agent, enhanced the expression of CHOP and DR5 induced
      by GGS and sensitized cells to GGS/TRAIL-induced apoptosis. Thus, GGS-induced
      eIF2alpha phosphorylation seems to be important for CHOP and DR5 upregulation.
      Furthermore, these events were accompanied by an increase in the generation of
      reactive oxygen species. Pretreatment with N-acetyl-L-cysteine and glutathione
      inhibited GGS-induced ER-stress, and CHOP and DR5 upregulation and almost
      completely blocked GGS/TRAIL-induced apoptosis. These results collectively
      indicate that DR5 induction via eIF-2alpha and CHOP is crucial for the marked
      synergistic effects induced by TRAIL and GGS. Taken together, these results
      indicate that a GGS/TRAIL combination could represent a novel important tool for
      cancer therapy.

PMID- 21903094
TI  - Caspase-8, c-FLIP, and caspase-9 in c-Myc-induced apoptosis of fibroblasts.
AB  - c-Myc is known to induce or potentiate apoptotic processes predominantly by
      triggering or enhancing the activity of caspases, but the activation mechanisms
      of caspases by c-Myc remain still poorly understood. Here we found that in
      MycERTM rat fibroblasts the activation of c-Myc led to an early activation and
      cleavage of the initiator caspase-8, and concurrent processing and activation of
      the effector caspases 3 and 7. Interestingly, the expression of cellular FLICE
      inhibitory protein (c-FLIP) mRNA and the encoded protein, c-FLIP(L), a
      catalytically inactive homologue of caspase-8, were down-regulated prior to or
      coincidently with the activation of caspase-8. Of the other known initiators,
      caspase-9, involved in the mitochondrial pathway, was activated/processed
      surprisingly late, only after the effector caspases 3/7. Further, we studied the
      potential involvement of the Fas- and tumor necrosis factor receptor (TNFR)
      mediated signaling in the activation of caspase-8 by c-Myc. Blocking of the
      function of these death receptors by neutralizing antibodies against Fas ligand
      and TNF-alpha did not prevent the processing of caspase-8 or cell death. c-Myc
      was neither found to induce any changes in the expression of TNF-related
      apoptosis inducing ligand (TRAIL) or its receptor. These data suggest that
      caspase-8 does not become activated through an extrinsic but an
      "intrinsic/intracellular" apoptotic pathway unleashed by the down-regulation of c
      FLIP by c-Myc. Moreover, ectopic expression of c-FLIP(L) inhibited the c-Myc
      induced apoptosis.

PMID- 21903096
TI  - RGK family G-domain:GTP analog complex structures and nucleotide-binding
      properties.
AB  - The RGK family of small G-proteins, including Rad, Gem, Rem1, and Rem2, is
      inducibly expressed in various mammalian tissues and interacts with voltage
      dependent calcium channels and Rho kinase. Many questions remain regarding their
      physiological roles and molecular mechanism. Previous crystallographic studies
      reported RGK G-domain:guanosine di-phosphate structures. To test whether RGK
      proteins undergo a nucleotide-induced conformational change, we determined the
      crystallographic structures of Rad:GppNHp and Rem2:GppNHp to 1.7 and 1.8 A
      resolutions, respectively. Also, we characterized the nucleotide-binding
      properties and conformations for Gem, Rad, and several structure-based mutants
      using fluorescence spectroscopy. The results suggest that RGK G-proteins may not
      behave as Ras-like canonical nucleotide-induced molecular switches. Further, the
      RGK proteins have differing structures and nucleotide-binding properties, which
      may have implications for their varied action on effectors.

PMID- 21903095
TI  - Development and validation of a standardized ELISA for the detection of soluble
      Fc-epsilon-RI in human serum.
AB  - The aim of this study was to develop a standardized enzyme-linked immunosorbent
      assay (ELISA) for detection of human soluble Fc-epsilon-RI (sFcepsilonRI), a
      serum isoform of the high affinity IgE receptor. A recombinant version of
      sFcepsilonRI was produced in baculovirus and used as standard. ELISA plates were
      coated with anti-mouse IgG followed by incubation with the monoclonal capture
      antibody CRA1. This FcepsilonRI-alpha-specific antibody binds to the stalk region
      of the protein and does not inhibit IgE-binding. After incubation with standards
      or serum samples, plates were incubated with chimeric IgE followed by detection
      with horseradish peroxidase conjugated anti-human IgE. Enzymatic activity was
      visualized with (3,3',5,5')-tetramethylbenzidine. Specificity was demonstrated by
      omission of capture or detection reagents. Units (U) of detection were
      established and the dynamic range of the assay was defined as 10-640 U/ml for a
      1/5 serum dilution. Parameters of linearity (R(2)>0.999), matrix interference
      test (recovery of 70-110%), intra-assay variability (coefficient of variation
      (CV) <20%) and inter-assay variability (CV <20%) met acceptance criteria for
      immunoassay validation. Correlation analysis of serum units of sFcepsilonRI
      measured with the new ELISA and serum IgE levels confirmed earlier published data
      describing a weak correlation of the two parameters in patients with elevated
      serum IgE while no correlation in patients with normal serum IgE or the total
      patient group was found. In summary, we established and validated a standardized
      ELISA for the detection of sFcepsilonRI. This novel method now allows for
      comparative analysis of sFcepsilonRI levels in health and disease.

PMID- 21903097
TI  - Inhibition of cullin RING ligases by cycle inhibiting factor: evidence for
      interference with Nedd8-induced conformational control.
AB  - Cycle inhibiting factor (Cif) is produced by pathogenic intracellular bacteria
      and injected into the host cells via a type III secretion system. Cif is known to
      interfere with the eukaryotic cell cycle by inhibiting the function of cullin
      RING E3 ubiquitin ligases (CRLs). Cullin proteins form the scaffold protein of
      CRLs and are modified with the ubiquitin-like protein Nedd8, which exerts
      important conformational control required for CRL activity. Cif has recently been
      shown to catalyze the deamidation of Gln40 in Nedd8 to Glu. Here, we addressed
      how Nedd8 deamidation inhibits CRL activity. Our results indicate that
      Burkholderia pseudomallei Cif (also known as CHBP) inhibits the deconjugation of
      Nedd8 in vivo by inhibiting binding of the deneddylating COP9 signalosome (CSN)
      complex. We provide evidence that the reduced binding of CSN and the inhibition
      of CRL activity by Cif are due to interference with Nedd8-induced conformational
      control, which is dependent on the interaction between the Nedd8 hydrophobic
      patch and the cullin winged-helix B subdomain. Of note, mutation of Gln40 to Glu
      in ubiquitin, an additional target of Cif, inhibits the interaction between the
      hydrophobic surface of ubiquitin and the ubiquitin-binding protein p62/SQSTM1,
      showing conceptually that Cif activity can impair ubiquitin/ubiquitin-like
      protein non-covalent interactions. Our results also suggest that Cif may exert
      additional cellular effects by interfering with the association between ubiquitin
      and ubiquitin-binding proteins.

PMID- 21903099
TI  - Morphological changes in early melanoma development: influence of nutrients,
      growth inhibitors and cell-adhesion mechanisms.
AB  - Current diagnostic methods for skin cancers are based on some morphological
      characteristics of the pigmented skin lesions, including the geometry of their
      contour. The aim of this article is to model the early growth of melanoma
      accounting for the biomechanical characteristics of the tumor micro-environment,
      and evaluating their influence on the tumor morphology and its evolution. The
      spatial distribution of tumor cells and diffusing molecules are explicitly
      described in a three-dimensional multiphase model, which incorporates general
      cell-to-cell mechanical interactions, a dependence of cell proliferation on
      contact inhibition, as well as a local diffusion of nutrients and inhibiting
      molecules. A two-dimensional model is derived in a lubrication limit accounting
      for the thin geometry of the epidermis. First, the dynamical and spatial
      properties of planar and circular tumor fronts are studied, with both numerical
      and analytical techniques. A WKB method is then developed in order to analyze the
      solution of the governing partial differential equations and to derive the
      threshold conditions for a contour instability of the growing tumor. A control
      parameter and a critical wavelength are identified, showing that high cell
      proliferation, high cell adhesion, large tumor radius and slow tumor growth
      correlate with the occurrence of a contour instability. Finally, comparing the
      theoretical results with a large amount of clinical data we show that our
      predictions describe accurately both the morphology of melanoma observed in vivo
      and its variations with the tumor growth rate. This study represents a
      fundamental step to understand more complex microstructural patterns observed
      during skin tumor growth. Its results have important implications for the
      improvement of the diagnostic methods for melanoma, possibly driving progress
      towards a personalized screening.

PMID- 21903098
TI  - On unsatisfied hydrogen bonds in the N-terminal subdomain of villin headpiece.
AB  - Villin headpiece is a small autonomously folding protein that has emerged as a
      model system for understanding the fundamental tenets governing protein folding.
      In this communication, we employ NMR and X-ray crystallography to characterize a
      point mutant, H41F, which retains actin-binding activity, is more thermostable
      but, interestingly, does not exhibit the partially folded intermediate observed
      of either wild-type or other similar point mutants.

PMID- 21903100
TI  - Evolution of altruistic punishment in heterogeneous populations.
AB  - Evolutionary models for altruistic behavior typically make the assumption of
      homogeneity: each individual has the same costs and benefits associated with
      cooperating with each other and punishing for selfish behavior. In this paper, we
      relax this assumption by separating the population into heterogeneous classes,
      such that individuals from different classes differ in their ability to punish
      for selfishness. We compare the effects of introducing heterogeneity this way
      across two population models, that each represents a different type of
      population: the infinite and well-mixed population describes the way workers of
      social insects such as ants are organized, while a spatially structured
      population is more related to the way social norms evolve and are maintained in a
      social network. We find that heterogeneity in the effectiveness of punishment by
      itself has little to no effect on whether or not altruistic behavior will
      stabilize in a population. In contrast, heterogeneity in the cost that
      individuals pay to punish for selfish behavior allows altruistic behavior to be
      maintained more easily. Fewer punishers are needed to deter selfish behavior, and
      the individuals that punish will mostly belong to the class that pays a lower
      cost to do so. This effect is amplified when individuals that pay a lower cost
      for punishing inflict a higher punishment. The two population models differ when
      individuals that pay a low cost for punishing also inflict a lower punishment. In
      this situation, altruistic behavior becomes harder to maintain in an infinite and
      well-mixed population. However, this effect does not occur when the population is
      spatially structured.

PMID- 21903101
TI  - Invasion of infectious diseases in finite homogeneous populations.
AB  - We consider the initial invasion of an infectious disease in a finite,
      homogeneous population. Methodology for evaluating the basic reproduction number,
      R(0), and the probability mass function of secondary infections is presented. The
      impact of finite population size, and infectious period distribution (between
      exponential, two-phase gamma, and constant), is assessed. Implications for
      infectious disease invasion and estimation of infectious disease model and
      parameters from data of secondary infections by initially infected individuals in
      naive, finite, homogeneous populations are reported. As any individual interacts
      with a finite number of contacts during their infectious period, these results
      are important to the study of infectious disease dynamics.

PMID- 21903102
TI  - Mathematical modeling on obligate mutualism: Interactions between leaf-cutter
      ants and their fungus garden.
AB  - We propose a simple mathematical model by applying Michaelis-Menton equations of
      enzyme kinetics to study the mutualistic interaction between the leaf cutter ant
      and its fungus garden at the early stage of colony expansion. We derive
      sufficient conditions on the extinction and coexistence of these two species. In
      addition, we give a region of initial condition that leads to the extinction of
      two species when the model has an interior attractor. Our global analysis
      indicates that the division of labor by worker ants and initial conditions are
      two important factors that determine whether leaf cutter ants' colonies and their
      fungus garden can survive and grow or not. We validate the model by comparing
      model simulations and data on fungal and ant colony growth rates under laboratory
      conditions. We perform sensitive analysis of the model based on the experimental
      data to gain more biological insights on ecological interactions between leaf
      cutter ants and their fungus garden. Finally, we give conclusions and discuss
      potential future work.

PMID- 21903103
TI  - The roles of the Moran effect and dispersal in synchronizing oscillating
      populations.
AB  - Patterns of spatial synchrony of population dynamics are dramatic phenomena that
      provide the potential for unraveling forces controlling the dynamics of natural
      populations in time and space. Prior ecological research has focused on attention
      to either deterministic or stochastic forces acting separately, with an emphasis
      on long term behavior, or on small systems consisting often of two interacting
      spatial locations. Using ideas from the dynamics of weakly coupled oscillators
      with an emphasis on the temporal dynamics of synchrony we develop a synthetic
      approach that explains patterns of synchrony as the result of an interplay
      between deterministic and stochastic forces. The temporal scale of convergence
      can provide a useful tool for determining the relative importance of
      deterministic and stochastic influences. Our approach applies both to specific
      systems that have been previously analyzed such as disease dynamics, and to a
      range of exploiter victim systems.

PMID- 21903104
TI  - A model for Vibrio cholerae colonization of the human intestine.
AB  - Vibrio cholerae is a strict human pathogen that causes the disease cholera. It is
      an old-world pathogen that has re-emerged as a new threat since the early 1990s.
      V. cholerae colonizes the upper, small intestine where it produces a toxin that
      leads to watery diarrhea, characterizing the disease (Kahn et al., 1988). The
      dynamics of colonization by the bacteria of the intestines are largely unknown.
      Although a large initial infectious dose is required for infection, data suggests
      that only a smaller sub-population colonizes a portion of the small bowel leading
      to disease. There are many barriers to colonization in the intestines including
      peristalsis, fluid wash-out, viscosity of the mucus layer, and pH. We are
      interested in identifying the mechanisms that allow this sub-population of
      bacteria to survive and colonize the intestines when faced with these barriers.
      To elaborate the dynamics of V. cholerae infection, we have developed a
      mathematical model based on a convection-diffusion-reaction-swimming equation
      capturing bacterial dynamics coupled with Stokes equations governing fluid
      velocity where we developed a novel non-local boundary condition. Our results
      indicate that both host and bacterial factors contribute to bacterial density in
      the gut. Host factors include intestinal diffusion and convection rates while
      bacterial factors include adherence, motility and growth rates. This model can
      ultimately be used to test therapeutic strategies against V. cholerae.

PMID- 21903105
TI  - Anxiety in Parkinson's disease: a critical review of experimental and clinical
      studies.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder
      affecting about 1% of the population older than 60 years. Classically, PD is
      considered as a movement disorder, and its diagnosis is based on the presence of
      a set of cardinal motor signs that are the consequence of a pronounced death of
      dopaminergic neurons in the substantia nigra pars compacta. There is now
      considerable evidence showing that the neurodegenerative processes leading to
      sporadic PD begin many years before the appearance of the characteristic motor
      symptoms, and that additional neuronal fields and neurotransmitter systems are
      also involved in PD, including olfactory structures, amygdala, caudal raphe
      nuclei, locus coeruleus, and hippocampus. Accordingly, adrenergic and
      serotonergic neurons are also lost, which seems to contribute to the anxiety in
      PD. Non-motor features of PD usually do not respond to dopaminergic medication
      and probably form the major current challenge in the clinical management of PD.
      Additionally, most studies performed with animal models of PD have investigated
      their ability to induce motor alterations associated with advanced phases of PD,
      and some studies begin to assess non-motor behavioral features of the disease.
      The present review attempts to examine results obtained from clinical and
      experimental studies to provide a comprehensive picture of the neurobiology and
      current and potential treatments for anxiety in PD. The data reviewed here
      indicate that, despite their high prevalence and impact on the quality of life,
      anxiety disorders are often under-diagnosed and under-treated in PD patients.
      Moreover, there are currently few clinical and pre-clinical studies underway to
      investigate new pharmacological agents for relieving these symptoms, and we hope
      that this article may inspire clinicians and researchers devote to the studies on
      anxiety in PD to change this scenario. This article is part of a Special Issue
      entitled 'Anxiety and Depression'.

PMID- 21903106
TI  - Scopolamine impairs behavioural function and arginine metabolism in the rat
      dentate gyrus.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder with progressive memory
      loss. It has been shown that the cholinergic neurotransmission deficit is one of
      the neurochemical characteristics of AD, and that L-arginine and its metabolites
      also play a prominent role in AD pathogenesis. Scopolamine, a non-selective
      muscarinic receptor antagonist, blocks cholinergic neurotransmission and impairs
      behavioural function, including learning and memory. This study investigated the
      effects of scopolamine on animals' behavioural performance and L-arginine
      metabolism in the hippocampus and prefrontal cortex. Rats were given
      intraperitoneal injections of scopolamine (0.8 mg/kg) or saline (1 ml/kg) and
      tested in the Y-maze, open field, water maze and elevated plus maze 30 min post
      treatment. After completion of the behavioural testing, the CA1, CA2/3 and
      dentate gyrus (DG) sub-regions of the hippocampus and the prefrontal cortex were
      harvested to measure the activity and protein expression of nitric oxide synthase
      (NOS) and arginase, and the levels of L-arginine, L-citrulline, L-ornithine,
      agmatine, putrescine, spermidine, spermine, glutamate and GABA. Scopolamine
      treated rats displayed reduced alternation and exploratory behaviour, increased
      swimming speed and impaired spatial learning and memory. There were significantly
      decreased NOS activity, increased arginase activity, and increased L-ornithine
      and putrescine levels in the DG, but not other regions examined, in the
      scopolamine treated rats as compared to the controls. These findings suggest that
      scopolamine impairs behavioural function and alters L-arginine metabolism in the
      DG sub-region of the hippocampus specifically. The underlying mechanisms of it
      remain to be explored further.

PMID- 21903107
TI  - alphaCaMKII autophosphorylation controls exploratory activity to threatening
      novel stimuli.
AB  - Autophosphorylation of alphaCaMKII is regarded as a 'molecular memory' for Ca(2+)
      transients and a crucial mechanism in aversely, but less so in appetitively,
      motivated learning and memory. While there is a growing body of research
      implicating alphaCaMKII in general in behavioral responses to threat or fearful
      stimuli, little is known about the contribution of the autophosphorylation. The
      present study asked how alphaCaMKII autophosphorylation controls anxiety-like
      behavioral responses toward novel, potentially threatening stimuli. We tested
      homozygous and heterozygous T286A alphaCaMKII autophosphorylation deficient mice
      and wild types in a systematic series of behavioral tests. Homozygous mutants
      were more active in the open field test and showed reduced anxiety-related
      behavior in the light/dark test, but these findings were confounded by a
      hyperlocomotor phenotype. The analysis of elevated plus maze showed significantly
      reduced anxiety-related behavior in the alphaCaMKII autophosphorylation-deficient
      mice which appeared to mediate a hyperlocomotor response. An analysis of home
      cage behavior, where neither novel nor threatening stimuli were present, showed
      no differences in locomotor activity between genotypes. Increased locomotion was
      not observed in the novel object exploration test in the alphaCaMKII
      autophosphorylation-deficient mice, implying that hyperactivity does not occur in
      response to discrete novel stimuli. The present data suggest that the behavior of
      alphaCaMKII autophosphorylation-deficient mice cannot simply be described as a
      low anxiety phenotype. Instead it is suggested that alphaCaMKII
      autophosphorylation influences locomotor reactivity to novel environments that
      are potentially, but not necessarily threatening.

PMID- 21903108
TI  - Cognitive dysfunctions induced by a cholinergic blockade and Abeta 25-35 peptide
      are attenuated by salvianolic acid B.
AB  - Alzheimer's disease (AD) is a neurodegenerative disorder associated with
      progressive cognitive and memory loss and neuronal cell death. Current
      therapeutic strategies for AD are very limited; thus, traditional herbal
      medicines or their active constituents receive much attention. The aim of this
      study was to investigate the cognitive enhancing effects of salvianolic acid B
      (SalB) isolated from Salvia miltiorrhiza and its ameliorating effects on various
      drug-induced amnesic models using the passive avoidance, Y-maze, and Morris water
      maze tasks. Drug-induced amnesia was induced by administering scopolamine,
      diazepam, muscimol, or amyloid-beta (Abeta)(25-35) peptide. SalB (10 mg/kg, p.o.)
      was found to significantly reverse the cognitive impairments induced by
      scopolamine (1 mg/kg, i.p.) or Abeta(25-35) (10 nmol/5 MUl, i.c.v.) injection.
      This ameliorating effect of SalB was antagonized by the GABA(A) receptor
      agonists, muscimol or diazepam, respectively. In addition, SalB alone was capable
      of improving cognitive performances. Furthermore, SalB (100 MUM) was found to
      inhibit GABA-induced outward Cl(-) currents in single hippocampal CA1 neuron.
      These results suggest that the observed ameliorations of cholinergic dysfunction-
      or Abeta(25-35)-induced memory impairment by SalB were mediated, in part, via the
      GABAergic neurotransmitter system after a single administration.

PMID- 21903110
TI  - Ethanol protects cultured neurons against amyloid-beta and alpha-synuclein
      induced synapse damage.
AB  - The loss of synapses and a corresponding reduction in synaptic proteins are
      histopathological features of Alzheimer's disease that correlate strongly with
      dementia. Here we report that stable Abeta oligomers secreted by 7PA2 cells
      reduced the amount of synaptophysin, a protein used as an indicator of synapse
      density, in cultured cortical and hippocampal neurons. Pre-treatment with
      physiologically relevant concentrations of ethanol (0.02-0.08%) protected neurons
      against Abeta-induced synapse damage. Ethanol also protected neurons against
      synapse damage induced by alpha-synuclein (alphaSN), pre-synaptic aggregates of
      which are characteristic of Parkinson's disease and dementia with Lewy bodies.
      Exposure of neurons to ethanol did not affect the accumulation of Abeta at
      synapses, rather it reduced the Abeta and alphaSN-induced activation of
      cytoplasmic phospholipase A(2) (cPLA(2)) within synapses. Ethanol did not affect
      synapse damage caused by platelet-activating factor or prostaglandin E(2),
      bioactive lipids that are formed following the activation of cPLA(2). These
      results may help explain epidemiological reports that moderate alcohol
      consumption protects against the development of dementia in Alzheimer's and
      Parkinson's diseases.

PMID- 21903109
TI  - The dynamic role of beta-catenin in synaptic plasticity.
AB  - In addition to its role in development and cell proliferation, beta-catenin has
      been implicated in neuronal synapse regulation and remodeling. Here we review
      basic molecular and structural mechanisms of synaptic plasticity, followed by a
      description of the structure and function of beta-catenin. We then describe a
      role for beta-catenin in the cellular processes underlying synaptic plasticity.
      We also review recent data demonstrating that beta-catenin mRNA and protein
      phosphorylation are dynamically regulated during fear memory consolidation in
      adult animals. Such alterations are correlated with a change in the association
      of beta-catenin with cadherin, and deletion of the beta-catenin gene prevents
      fear learning. Overall, the extant data suggest that beta-catenin may function in
      mediating the structural changes associated with memory formation. This suggests
      a general role for beta-catenin in synaptic remodeling and stabilization
      underlying long-term memory in adults, and possible roles for dysfunction in the
      beta-catenin pathway in disorders of memory impairment (e.g. Alzheimer's Disease)
      and in disturbances in which emotional memories are too strong or resistant to
      inhibition (e.g. fear learning in Posttraumatic Stress Disorder). Further
      understanding of the beta-catenin pathway may lead to better appreciation for the
      structural mechanisms underlying learning and memory as well as provide novel
      therapeutic approaches in memory related disorders. This article is part of a
      Special Issue entitled 'Anxiety and Depression'.

PMID- 21903111
TI  - A time-dependent role of midline thalamic nuclei in the retrieval of fear memory.
AB  - Increasing evidence indicates that the medial prefrontal cortex (mPFC) and the
      amygdala mediate expression and extinction of conditioned fear, but few studies
      have examined the inputs to these structures. The dorsal part of the midline
      thalamus (dMT) contains structures such as the mediodorsal nucleus,
      paraventricular nucleus, and paratenial nucleus that project prominently to mPFC,
      as well as to basal (BA) and central (Ce) nuclei of the amygdala. Using temporary
      inactivation with GABA agonist muscimol, we found that dMT was necessary for
      retrieving auditory fear memory that was 24 h old, but not 2-8 h old. However,
      pre-training infusions did not impair fear acquisition or extinction. To
      determine the possible targets of dMT that might modulate fear retrieval, we
      combined dMT inactivation with Fos immunohistochemistry. Rats with inactivation
      induced impairment in fear retrieval showed increased Fos in the lateral division
      of Ce (CeL), and decreased Fos in the medial division of Ce. No differences in
      Fos expression were observed in the mPFC or BA. We suggest that the projections
      from the paraventricular nucleus to CeL are involved in retrieval of well
      consolidated fear memories. This article is part of a Special Issue entitled
      'Anxiety and Depression'.

PMID- 21903112
TI  - Intact attentional processing but abnormal responding in M1 muscarinic receptor
      deficient mice using an automated touchscreen method.
AB  - Cholinergic receptors have been implicated in schizophrenia, Alzheimer's disease,
      Parkinson's disease, and Huntington's disease. However, to better target
      therapeutically the appropriate receptor subsystems, we need to understand more
      about the functions of those subsystems. In the current series of experiments, we
      assessed the functional role of M(1) receptors in cognition by testing M(1)
      receptor-deficient mice (M1R(-/-)) on the five-choice serial reaction time test
      of attentional and response functions, carried out using a computer-automated
      touchscreen test system. In addition, we tested these mice on several tasks
      featuring learning, memory and perceptual challenges. An advantage of the
      touchscreen method is that each test in the battery is carried out in the same
      task setting, using the same types of stimuli, responses and feedback, thus
      providing a high level of control and task comparability. The surprising finding,
      given the predominance of the M(1) receptor in cortex, was the complete lack of
      effect of M(1) deletion on measures of attentional function per se. Moreover,
      M1R(-/-) mice performed relatively normally on tests of learning, memory and
      perception, although they were impaired in object recognition memory with, but
      not without an interposed delay interval. They did, however, show clear
      abnormalities on a variety of response measures: M1R(-/-) mice displayed fewer
      omissions, more premature responses, and increased perseverative responding
      compared to wild-types. These data suggest that M1R(-/-) mice display abnormal
      responding in the face of relatively preserved attention, learning and
      perception.

PMID- 21903113
TI  - Biodistribution and brain permeability of the extracellular domain of neuregulin
      1-beta1.
AB  - Neuregulin-1 (NRG1) belongs to a large family of growth and differentiation
      factors with a key role in the development and maintenance of the brain. Genetic
      association of NRG1 within brain disorders such as Alzheimer's disease,
      schizophrenia and neuroprotective properties of certain NRG1 isoforms have led to
      a variety of studies in corresponding disease models. In the present work, we
      investigated NRG1 with regard to its peripheral and central biodistribution after
      systemic application. We first-time radiolabeled the entire biologically active
      extracellular domain of NRG1 isotype-beta1 (NRG1-beta1 ECD; aa 2-246) with iodine
      125 and administered it peripherally to healthy adult C57Bl6 mice. Blood kinetics
      and relative organ distribution of (125)I-labeled NRG1-beta1 ECD were determined.
      The blood level of NRG1-beta1 ECD peaked within the first hour after
      intraperitoneal (i.p.) application. The brain-blood ratios of (125)I-labeled NRG1
      beta1 ECD were time-dependently 150-370% higher compared to the brain impermeable
      control, (131)I-labeled bovine serum albumin. Autoradiographs of brain slices
      demonstrated that (125)I-labeled NRG1-beta1 ECD accumulated in several regions of
      the brain e.g. frontal cortex, striatum and ventral midbrain containing the
      substantia nigra. In addition we found histochemical and biochemical evidence
      that phosphorylation of the NRG1 prototype receptor ErbB4 was increased in these
      regions after systemic application of NRG1-beta1 ECD. Our data suggest that NRG1
      beta1 ECD passes the blood-brain barrier and activates cerebral ErbB4 receptors.

PMID- 21903114
TI  - Social stress-induced hypothyroidism is attenuated by antidepressant treatment in
      rats.
AB  - Although serotonergic system has been classically implicated in mood modulation,
      there has been relatively little study on the relationship between this system
      and thyroid hormones (TH) economy in stress models. When TH are studied, the
      effects of stress on thyroid function seems to be complex and depend on the kind
      and time of stress which counts for the elusiveness of mechanisms underlying
      changes in TH economy. Herein, we hypothesized that serum TH are affected in a
      time-dependent fashion after repeated social stressful stimuli and serotonergic
      system is implicated in these changes. Therefore, we aimed to investigate the
      possible alterations in thyroid hormone economy and type 1 (D1) and type 2 (D2)
      deiodinase activity in a model of social defeat stress. Thereafter, we tested the
      responsiveness of these changes to fluoxetine treatment. Both short (STS) and a
      long-term (LTS) stress were performed. Blood samples were drawn just before and 1
      (STS) or 4 and 8 weeks (LTS) after the beginning of stress to assess serum T4, T3
      and corticosterone. Deiodinases activity was assessed at the end of each
      protocol. Stress-induced behavior studied in open field arena and
      hypercorticosteronemia were mainly observed in LTS (week 4). Stress-induced
      behavior was associated to hypothyroidism which occurred before, since week 1 in
      stressed group. Serum TH was restored to control levels in week 8, when behavior
      changes were not observed anymore, and was mainly associated with high brown
      adipose tissue D2 activity since thyroid and liver D1 activity were low or normal
      in the STS and LTS respectively in stressed rats compared to control.
      Antidepressant study revealed that fluoxetine treatment (10mg/kg po during four
      weeks) fully reversed stress-induced behavior and normalized serum T4, but not T3
      levels and hypercorticosteronemia in stressed group compared to control. The
      current work adds new concepts concerning TH metabolism changes induced by social
      stress and suggests that serotonergic system impairment may take part in the key
      events which ultimately lead to hypothyroxinemia and behavioral changes induced
      by chronic social defeat. This article is part of a Special Issue entitled
      'Anxiety and Depression'.

PMID- 21903115
TI  - Involvement of the mammalian target of rapamycin signaling in the antidepressant
      like effect of group II metabotropic glutamate receptor antagonists.
AB  - Growing evidence has indicated that the blockade of group II metabotropic
      glutamate (mGlu2/3) receptor exerts antidepressant-like effects in several animal
      models of depression. However, the molecular mechanisms underlying the action of
      mGlu2/3 receptor antagonists are not well understood. Here, we investigated the
      involvement of mammalian target of rapamycin (mTOR) signaling in the acute and
      sustained antidepressant-like effects of mGlu2/3 receptor antagonists such as
      (1R, 2R, 3R, 5R, 6R)-2-amino-3-(3,4-dichlorobenzyloxy)-6
      fluorobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (MGS0039) and (2S)-2-amino-2
      [(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495). Mice
      were subjected to a tail suspension test (TST) to assess the acute and sustained
      antidepressant-like effects. We evaluated the effect of rapamycin, an mTOR
      antagonist, on the acute and sustained antidepressant-like effects of mGlu2/3
      receptor antagonists. Both MGS0039 and LY341495 exerted antidepressant-like
      effects, as evaluated using the TST; these effects were sustained for 24 h.
      Pretreatment with rapamycin blocked the sustained, but not the acute,
      antidepressant-like effects of mGlu2/3 receptor antagonists, as observed in
      ketamine. The present result suggests that the blockade of the mGlu2/3 receptor
      may activate mTOR signaling, and that the activation of mTOR signaling may
      contribute to the sustained antidepressant-like effects of mGlu2/3 receptor
      antagonists.

PMID- 21903116
TI  - Absence of tolerance to the anticonvulsant and neuroprotective effects of
      imidazenil against DFP-induced seizure and neuronal damage.
AB  - The clinical use of diazepam or midazolam to control organophosphate (OP) nerve
      agent-induced seizure activity is limited by their unwanted effects including
      sedation, amnesia, withdrawal, and anticonvulsant tolerance. Imidazenil is an
      imidazo-benzodiazepine derivative with high intrinsic efficacy and selectivity
      for alpha2-, alpha3-, and alpha5- but low intrinsic efficacy for alpha1
      containing GABA(A) receptors. We have previously shown that imidazenil is more
      efficacious than diazepam at protecting rats and mice from diisopropyl
      fluorophosphate (DFP)-induced seizures and neuronal damage without producing
      sedation. In the present study, we compared the tolerance liability of imidazenil
      and diazepam to attenuate the seizure activity and neurotoxic effects of DFP.
      Rats received protracted (14 days) oral treatment with increasing doses of
      imidazenil (1-4 mg/kg), diazepam (5-20 mg/kg), or vehicle. Eighteen hours after
      the last dose of the protracted treatment schedule, rats were tested for
      anticonvulsant tolerance after a 30 min pretreatment with a single test dose of
      imidazenil (0.5 mg/kg) or diazepam (5 mg/kg) prior to a DFP challenge (1.5
      mg/kg). The anticonvulsant (modified Racine score scale) and neuroprotective
      (fluoro-jade B staining) effects of diazepam were significantly reduced in
      protracted diazepam-treated animals whereas the effects of imidazenil were not
      altered in protracted imidazenil-treated animals. The present findings indicate
      that protracted imidazenil treatment does not produce tolerance to its protective
      action against the neurotoxic effects of OP exposure.

PMID- 21903117
TI  - Chronic treatment with the opioid antagonist naltrexone favours the coupling of
      spinal cord MU-opioid receptors to Galphaz protein subunits.
AB  - Sustained administration of opioid antagonists to rodents results in an enhanced
      antinociceptive response to agonists. We investigated the changes in spinal MU
      opioid receptor signalling underlying this phenomenon. Rats received naltrexone
      (120 MUg/h; 7 days) via osmotic minipumps. The antinociceptive response to the MU
      agonist sufentanil was tested 24 h after naltrexone withdrawal. In spinal cord
      samples, we determined the interaction of MU-receptors with Galpha proteins
      (agonist-stimulated [(35)S]GTPgammaS binding and immunoprecipitation of
      [(35)S]GTPgammaS-labelled Galpha subunits) as well as MU-opioid receptor
      dependent inhibition of the adenylyl cyclase (AC) activity. Chronic naltrexone
      treatment augmented DAMGO-stimulated [(35)S]GTPgammaS binding, potentiated the
      inhibitory effect of DAMGO on the AC/cAMP pathway, and increased the inverse
      agonist effect of naltrexone on cAMP accumulation. In control rats, the
      inhibitory effect of DAMGO on cAMP production was antagonized by pertussis toxin
      (PTX) whereas, after chronic naltrexone, the effect became resistant to the
      toxin, suggesting a coupling of MU-receptors to PTX-insensitive Galpha(z)
      subunits. Immunoprecipitation assays confirmed the transduction switch from
      Galpha(i/o) to Galpha(z) proteins. The consequence was an enhancement of the
      antinociceptive response to sufentanil that, in consonance with the neurochemical
      data, was prevented by Galpha(z)-antisense oligodeoxyribonucleotides but not by
      PTX. Such changes in opioid receptor signalling can be a double-edged sword. On
      the one hand, they may have potential applicability to the optimisation of the
      analgesic effects of opioid drugs for the control of pain. On the other hand,
      they represent an important homeostatic dysregulation of the endogenous opioid
      system that might account for undesirable effects in patients chronically treated
      with opioid antagonists. This article is part of a Special Issue entitled 'Post
      Traumatic Stress Disorder'.

PMID- 21903118
TI  - SEA0400, a specific Na+/Ca2+ exchange inhibitor, prevents dopaminergic
      neurotoxicity in an MPTP mouse model of Parkinson's disease.
AB  - We have recently shown that the Na(+)/Ca(2+) exchanger (NCX) is involved in
      nitric oxide (NO)-induced cytotoxicity in cultured astrocytes and neurons.
      However, there is no in vivo evidence suggesting the role of NCX in
      neurodegenerative disorders associated with NO. NO is implicated in the
      pathogenesis of neurodegenerative disorders such as Parkinson's disease. This
      study examined the effect of SEA0400, the specific NCX inhibitor, on 1-methyl-4
      phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity, a
      model of Parkinson's disease, in C57BL/6J mice. MPTP treatment (10 mg/kg, four
      times at 2-h intervals) decreased dopamine levels in the midbrain and impaired
      motor coordination, and these effects were counteracted by S
      methylthiocitrulline, a selective neuronal NO synthase inhibitor. SEA0400
      protected against the dopaminergic neurotoxicity (determined by dopamine levels
      in the midbrain and striatum, tyrosine hydroxylase immunoreactivity in the
      substantia nigra and striatum, striatal dopamine release, and motor deficits) in
      MPTP-treated mice. SEA0400 had no radical-scavenging activity. SEA0400 did not
      affect MPTP metabolism and MPTP-induced NO production and microglial activation,
      while it attenuated MPTP-induced increases in extracellular signal-regulated
      kinase (ERK) phosphorylation and lipid peroxidation product, thiobarbituric acid
      reactive substance. These findings suggest that SEA0400 protects against MPTP
      induced neurotoxicity probably by blocking ERK phosphorylation and lipid
      peroxidation which are downstream of NCX-mediated Ca(2+) influx.

PMID- 21903119
TI  - Slow perceptual processing at the core of developmental dyslexia: a parameter
      based assessment of visual attention.
AB  - The cognitive causes as well as the neurological and genetic basis of
      developmental dyslexia, a complex disorder of written language acquisition, are
      intensely discussed with regard to multiple-deficit models. Accumulating evidence
      has revealed dyslexics' impairments in a variety of tasks requiring visual
      attention. The heterogeneity of these experimental results, however, points to
      the need for measures that are sufficiently sensitive to differentiate between
      impaired and preserved attentional components within a unified framework. This
      first parameter-based group study of attentional components in developmental
      dyslexia addresses potentially altered attentional components that have recently
      been associated with parietal dysfunctions in dyslexia. We aimed to isolate the
      general attentional resources that might underlie reduced span performance, i.e.,
      either a deficient working memory storage capacity, or a slowing in visual
      perceptual processing speed, or both. Furthermore, by analysing attentional
      selectivity in dyslexia, we addressed a potential lateralized abnormality of
      visual attention, i.e., a previously suggested rightward spatial deviation
      compared to normal readers. We investigated a group of high-achieving young
      adults with persisting dyslexia and matched normal readers in an experimental
      whole report and a partial report of briefly presented letter arrays. Possible
      deviations in the parametric values of the dyslexic compared to the control group
      were taken as markers for the underlying deficit. The dyslexic group showed a
      striking reduction in perceptual processing speed (by 26% compared to controls)
      while their working memory storage capacity was in the normal range. In addition,
      a spatial deviation of attentional weighting compared to the control group was
      confirmed in dyslexic readers, which was larger in participants with a more
      severe dyslexic disorder. In general, the present study supports the relevance of
      perceptual processing speed in disorders of written language acquisition and
      demonstrates that the parametric assessment provides a suitable tool for
      specifying the underlying deficit within a unitary framework.

PMID- 21903120
TI  - Hypnosis meets neuropsychology: simulating visuospatial neglect in healthy
      participants.
AB  - Neglect patients are not aware of stimuli in the contralesional space. We aimed
      to simulate neglect-like behaviour in healthy participants, by asking them to
      orient their visuospatial attention in two conditions: non-hypnotic suggestion
      and post-hypnotic suggestion. Results showed that directing visuospatial
      attention to one side of space caused neglect of stimuli in the opposite side of
      space, but only when participants were under post-hypnotic suggestion.
      Furthermore, directing visuospatial attention to the right side of space caused
      more neglect of left-sided stimuli than directing visuospatial attention to the
      left side of space did for right-sided stimuli. We propose that post-hypnotic
      suggestion can be a useful tool for (de)activating neurocognitive mechanisms
      underlying visuospatial awareness, a function that is fundamental for our
      survival. The use of post-hypnotic suggestion could be applied to the study of
      many domains of cognitive neurosciences (e.g., neurocognitive rehabilitation).

PMID- 21903121
TI  - Head tilt in rats during exposure to a high magnetic field.
AB  - During exposure to high strength static magnetic fields, humans report vestibular
      symptoms such as vertigo, apparent motion, and nausea. Rodents also show signs of
      vestibular perturbation after magnetic field exposure at 7 tesla (T) and above,
      such as locomotor circling, activation of vestibular nuclei, and acquisition of
      conditioned taste aversions. We hypothesized that the acute effects of the
      magnetic field might be seen as changes in head position during exposure within
      the magnet. Using a yoked restraint tube that allowed movement of the head and
      neck, we found that rats showed an immediate and persistent deviation of the head
      during exposure to a static 14.1 T magnetic field. The direction of the head tilt
      was dependent on the orientation of the rat in the magnetic field (B), such that
      rats oriented head-up (snout towards B+) showed a rightward tilt of the head,
      while rats oriented head-down (snout towards B-) showed a leftward tilt of the
      head. The tilt of the head during magnet exposure was opposite to the direction
      of locomotor circling immediately after exposure observed previously. Rats
      exposed in the yoked restraint tube showed significantly more locomotor circling
      compared to rats exposed with the head restrained. There was little difference in
      CTA magnitude or extinction rate, however. The deviation of the head was seen
      when the rats were motionless within the homogenous static field; movement
      through the field or exposure to the steep gradients of the field was not
      necessary to elicit the apparent vestibulo-collic reflex.

PMID- 21903122
TI  - Relationships between early experience to dietary diversity, acceptance of novel
      flavors, and open field behavior in sheep.
AB  - This study determined whether early experiences by sheep to monotonous or diverse
      diets influence: (1) plasmatic profiles of cortisol, a hormone involved in stress
      responses by mammals, before and after an ACTH challenge, (2) the readiness to
      eat new foods in a new environment, (3) general fearfulness and response to
      separation--as measured by the open field test (OFT) and stress induced
      hyperthermia (SIH)--and (4) the link between (2) and (3). Thirty, 2-mo-old lambs
      were randomly assigned to 3 treatments (10 lambs/treatment). Lambs in one
      treatment (Diversity--DV) received in successive periods of exposure all possible
      4-way choice combinations of 2 foods high in energy and 2 foods high in protein
      from an array of 6 foods: 3 high in energy (beet pulp, oat grain, and a mix of
      grape pomace:milo [40:60]) and 3 high in protein (soybean meal, alfalfa, corn
      gluten meal). Lambs in another treatment (DV+T) received the same exposure
      described for DV but two phytochemicals, oxalic acid (1.5%) and quebracho tannins
      (10%) were randomly added within any period of exposure to foods high in energy
      or to foods high in protein. Lambs in the third treatment (Monotony--MO) received
      a monotonous balanced ration containing all 6 foods fed to the other groups.
      After exposure, lambs were offered a choice of the aforementioned 6 foods (DV;
      DV+T) or the monotonous diet (MO). Lambs were intravenously injected with ACTH 1
      h after food presentation, and sampled at 1, 2, and 3 h post feeding for
      determinations of plasma cortisol concentrations. Reluctance to eat novel
      flavored foods (onion-, coconut- and cinnamon-flavored wheat bran), open field
      behavior, and SIH was assessed in all treatments. Lambs in MO showed greater
      concentrations of plasma cortisol 1 h after food presentation than lambs in the
      DV or DV+T treatments (P=0.04). However, the difference was small and no
      differences among treatments were detected after an ACTH challenge (P>0.1). Lambs
      in DV consumed more onion-flavored wheat bran than lambs in MO (P=0.05). Lambs in
      DV also showed a greater cumulative consumption of novel flavors on d 2 than
      lambs in MO (treatment*day; P=0.01). Lambs in DV showed lower increase in rectal
      temperature (P=0.07) than lambs in MO. Only lambs in DV exhibited a positive
      relationship between consumption of cinnamon-flavored wheat bran and attempts of
      escape (R(2)=0.58; P=0.02). Our results suggest that exposure to diverse foods
      early in life may be less stressful than exposure to monotonous rations, as
      measured by plasma cortisol concentrations after food ingestion, and by changes
      in rectal temperature after exposure to the OFT. Lambs exposed to diverse diets
      early in life may also increase the initial acceptance of new flavors in novel
      environments relative to lambs exposed early in life to monotonous diets.

PMID- 21903123
TI  - Feeding behaviour after injection of alpha-adrenergic receptor agonists into the
      median raphe nucleus of food-deprived rats.
AB  - This study investigated the participation of median raphe nucleus (MnR) alpha1
      adrenergic receptors in the control of feeding behaviour. The alpha1-adrenergic
      agonist phenylephrine (PHE) and alpha2-adrenergic agonist clonidine (CLON) (at
      equimolar doses of 0, 6 and 20 nmol) were injected into the MnR of: a) rats
      submitted to overnight fasting (18 h); or b) rats maintained with 15 g of lab
      chow/day for 7 days. Immediately after the drug injections, the animals were
      placed in the feeding chamber and feeding and non-ingestive behaviours such as
      grooming, rearing, resting, sniffing and locomotion were recorded for 30 min. The
      results showed that both doses of PHE injected into the MnR of overnight fasted
      animals decreased food intake accompanied by an increase in the latency to start
      feeding. A reduction in feeding duration was observed only after treatment of the
      MnR with the 20 nmol dose of PHE. Both locomotion duration and sniffing frequency
      increased after injection with the highest dose PHE into the MnR. Feeding
      frequency and the other non-ingestive behaviours remained unchanged after PHE
      treatment in the MnR. Both doses of PHE injected into the MnR of food-restricted
      rats decreased food intake. This hypophagic response was accompanied by a
      decrease in feeding duration only after treatment of the MnR with the highest
      dose of PHE. The latency to start feeding and feeding frequency were not affected
      by injection of either dose of PHE into the MnR. While both doses of PHE
      increased sniffing duration, the highest dose of PHE increased resting duration
      and resting frequency. Treatment with CLON into the MnR did not affect feeding
      behaviour in either of the food deprivation conditions. The present results
      indicate the inhibitory functional role of alpha1-adrenergic receptors within the
      MnR on feeding behaviour.

PMID- 21903124
TI  - Development of affinity to the stockperson in lambs from two breeds.
AB  - The interactions between genetic and environmental factors on the development of
      lamb affinity to humans was assessed on 48 animals from two breeds (Gentile di
      Puglia and Comisana) and two treatments (Gentled and Not Gentled) producing 4
      groups (GPg, GPng, Cg, Cng, respectively). The Gentile di Puglia and Comisana
      gentled animals were subjected to a period of training consisting of gently
      handling each lamb for 5 min three times a day for the first week and then twice
      a week for three additional weeks. The gentling procedure included both tactile
      and visual/auditory interactions. At 30-32 days of age lambs were subjected to
      three arena tests conducted in a novel environment: i) isolation test (each
      animal was exposed to a novel environment, and isolated from tactile and visual
      contact with conspecifics for 5 min), ii) stationary human test (as previously
      but a human sitting in a corner of the pen), and iii) pen-mates' test (each
      animal was tested in the presence of 2 pen-mates whose behaviour was not
      recorded). During the 13 training sessions lambs exhibited an increasing number
      of contacts with the human and a decreasing number of bleats (P<0.001), although
      Gentile di Puglia lambs interacted more with the human (P<0.001) and tended to
      bleat less (P<0.10) than Comisana lambs. Lambs vocalised more and climbed more
      when tested in isolation as compared with lambs tested either with the human or
      with the pen-mates (P<0.01) and they vocalised more in the presence of the human
      than with the pen-mates (P<0.001). A higher number of contacts with the human
      stimulus was observed in gentled animals (P<0.05). However, differences between
      gentled and not gentled animals were only significant in Gentile di Puglia
      subjects (P<0.01). GPng lambs displayed the longest ambulatory activity during
      the isolation test (P<0.05) and exhibited more climbing attempts during the
      isolation test as compared with the human or the pen-mates' tests (P<0.001). A
      higher cortisol level was shown by GPng lambs in comparison with Cng subjects
      during the stationary human test (P<0.01), whereas no differences were detected
      between the two gentled groups. Gentling determined an improvement of the quality
      of human animal relationship in more reactive breeds such as Gentile di Puglia
      sheep.

PMID- 21903125
TI  - The effects of levofloxacin on rabbit anterior cruciate ligament cells in vitro.
AB  - Articular cartilage, epiphyseal growth plate and tendons have been recognized as
      targets of fluoroquinolone-induced connective tissue toxicity. The effects of
      fluoroquinolones on ligament tissues are still unknown. The aim of this study was
      to investigate the effects of levofloxacin, a typical fluoroquinolone antibiotic
      drug, on rabbit anterior cruciate ligament (ACL) cells in vitro. Rabbit ACL cells
      were treated with levofloxacin at different concentrations (0, 14, 28, 56, 112
      and 224 MUM) and were assessed to determine the possible cytotoxic effects of
      levofloxacin on ACL cells. Levofloxacin, with concentrations ranging from 28 to
      224 MUM, induced dose-dependent ACL cell apoptosis. Characteristic markers of
      programmed cell death and degenerative changes were identified by electron
      microscopy in the ACL cells treated with 28 MUM of levofloxacin. Moreover,
      levofloxacin significantly increased the mRNA expression of matrix
      metalloproteinase 3 (MMP-3) and MMP-13 and decreased the expression of tissue
      inhibitors of metalloproteinase 1 (TIMP-1) in a concentration-dependent manner;
      TIMP-3 and collagen type I alpha 1 (Col1A1) mRNA expression was not affected.
      Immunocytochemical analysis indicated that levofloxacin markedly increased the
      expression of active caspase-3 within a concentration range of 28 to 224 MUM,
      whereas a clear-cut decrease in Col1A1 expression was found with levofloxacin
      treatment concentrations of 112 and 224 MUM, compared to controls. Our data
      suggest that levofloxacin has cytotoxic effects on ACL cells characterized by
      enhanced apoptosis and decreased extracellular matrix, which suggest a potential
      adverse effect of fluoroquinolones.

PMID- 21903126
TI  - Isolation and identification of a snake venom metalloproteinase inhibitor from
      California ground squirrel (Spermophilus beecheyi) blood sera.
AB  - California ground squirrels (Spermophilus beecheyi) show blood-based defenses to
      a variety of toxins in the venom of the Northern Pacific rattlesnake (Crotalus
      oreganus oreganus). In this study we demonstrate the presence of an effective
      snake venom metalloproteinase inhibitor (SVMPI) in S. beecheyi. The blood sera of
      California ground squirrels were effective at reducing the metalloproteinase
      activity of Northern Pacific (C. o. oreganus) and prairie rattlesnake (Crotalus
      viridis viridis) venoms by over 75%, significantly more than its ability to
      reduce the activity of western diamondback rattlesnake venom. We used anion
      exchange and affinity chromatography to isolate this protein from the blood sera
      of S. beecheyi. This SVMPI had a molecular mass of 108.3 kDa and a pI of 5.1. The
      IC(50) of this inhibitor against whole venom from C. o. oreganus was determined
      to be 3.14 * 10(-8) M. Subsequent LC MS/MS analysis of a CNBr/tryptic digest of
      the inhibitor yielded multiple internal peptide sequences. These sequences showed
      homology to three other known mammalian plasma proteins: inter-alpha trypsin
      inhibitor, and two hibernation-associated proteins, HP25 and HP27. The presence
      of SVMPI in S. beecheyi blood sera is consistent with the resistance of these
      animals to venom-induced hemorrhage and tissue damage, and consistent with the
      protective factors conferring venom resistance in other mammals. However, the
      variety of SVMPI identified to date from mammalian taxa suggests that different
      species have converged on neutralization of venom metalloproteinase activity as a
      key step in venom neutralization.

PMID- 21903127
TI  - Parametric and pharmacological modulations of latent inhibition in mouse inbred
      strains.
AB  - Latent inhibition (LI) is a cross species selective attention phenomenon, which
      is disrupted by amphetamine and enhanced by antipsychotic drugs (APDs).
      Accumulating data of LI in gene-modified mice as well as in mouse inbred strains
      suggest genetic component of LI. Here we study modulation of LI in mouse inbred
      strains with spontaneously disrupted LI by parametric manipulations (number of
      pre-exposures and conditioning trials) and pharmacological treatments with
      antipsychotics and NMDA modulator, D-serine. C3H/He and CBA/J inbred mice showed
      disrupted LI under conditions with 40 pre-exposures (PE) and 2 trials of the
      conditioned stimulus-unconditioned stimulus (CS-US) due to either loss of the pre
      exposure effect or a ceiling effect of poor learning, respectively. The increased
      number of pre-exposures and/or number of conditioning trials corrected expression
      of LI in these inbred mice. The disrupted LI was also reversed by haloperidol in
      both inbred strains at 1.2 mg/kg but not at 0.4 mg/kg, as well as by clozapine
      (at 3 mg/kg in C3H/He and at 9 mg/kg in CBA/J mice). D-serine potentiated LI in
      C3H/He mice at 600 mg/kg, but not in the CBA/J at both studied doses (600 and
      1800 mg/kg). Desipramine (10 mg/kg) had no effect on LI in both inbred mouse
      strains. Our findings demonstrated some resemblance between the effects of
      parametric and pharmacological manipulations on LI, suggesting that APDs may
      affect the capacity of the brain processes environmental stimuli in LI. Taken
      together, LI may offer a translational strategy that allows prediction of drug
      efficacy for cognitive impairments in schizophrenia.

PMID- 21903128
TI  - Aromatic interactions at atom-to-atom contact and just beyond: a case study of
      protein interactions of NAD+/NADP+.
AB  - We probed aromatic-protein interactions based on specificity of enrichment of
      protein residues across a contact-based cutoff. Thus, 155 protein-NAD(+)/NADP(+)
      complexes were analyzed for enrichments within 10A of centroids of aromatic
      groups of the ligand when the residues were contacted and not contacted with the
      aromatic ligand. Specifically, neutral-adenine and cationic-nicotinamide groups
      of the oxidized coenzymes evoked interest to know whether the contrast of charge
      or the shared aromaticity will manifest in the enrichments across the cutoff. We
      found that when in contact, the enrichments are highly specific for nicotinamide
      and adenine-aromatic structures, and thus possibly complex in the basis, but when
      not in contact, they are generic for charge and aromaticity of the structures,
      and thus possibly specific in the basis. The order of enrichments over the
      contacted residues is Tyr>Cys>Thr>His>Asn>Ser>Met>Ile>Phe against nicotinamide
      pi(+) structure and Asp>Ile>Thr>His>Arg>Tyr>Gly>Val against adenine-pi structure,
      while the order over the non-contacted residues is
      Trp>Gly>His>Asn>Cys>Met>Tyr>Ser>Thr>Phe against nicotinamide-pi(+) structure and
      Asn>Thr>Ser>Gly>Cys>His>Val against adenine-pi structure. Neutral Trp, His, Tyr,
      and Phe, but not cationic Arg, are thus the non-contacted residues enriched
      specifically against nicotinamide-pi(+) structure, while Asn, Gly, Thr, Ser, and
      Cys are the non-contacted residues enriched generically against both the
      nicotinamide-pi(+) and adenine-pi aromatic structures. By analyzing the enriched
      groups in their geometric specificities, we found that, the enrichments against
      nicotinamide cation manifest the specificity expected of cation-pi interaction
      and against nicotinamide- and adenine-aromatic groups manifest the specificity
      expected of dipole-pi interaction. The cutoff-based method is proven valuable in
      probing protein-ligand interactions in the physics involved.

PMID- 21903129
TI  - Sugarcane Hsp101 is a hexameric chaperone that binds nucleotides.
AB  - The Clp/Hsp100 AAA+ chaperone family is involved in recovering aggregated
      proteins and little is known about other orthologs of the well studied ClpB from
      Escherichia coli and Hsp104 from Saccharomyces cerevisiae. Plant Hsp101 is a good
      model for understanding the relationship between the structure and function of
      Hsp100 proteins and to investigate the role of these chaperones in disaggregation
      processes. Here, we present the cloning and purification of a sugarcane ortholog,
      SHsp101, which is expressed in sugarcane cells and is a folded hexamer that is
      capable of binding nucleotides. Thus SHsp101 has the structural and functional
      characteristics of the Clp/Hsp100 AAA+ family.

PMID- 21903130
TI  - Polymer hydrogel from carboxymethyl guar gum and carbon nanotube for sustained
      trans-dermal release of diclofenac sodium.
AB  - Novel carboxymethyl guar gum (CMG)-chemically modified multiwalled carbon
      nanotube (MCNT) hybrid hydrogels were synthesized at different MCNT levels as
      potential device for sustained trans-dermal release of diclofenac sodium.
      Spectroscopy together with morphology, thermogravimetry, and rheological studies
      proved relatively strong CMG-MCNT interaction at 0.5 and 1 wt% levels of MCNT
      whereas de-wetting was increased with higher MCNT concentration. Drug
      encapsulation tendency increased with addition of MCNT; maximum entrapment was
      noticed at 1 wt% MCNT level. Hydrogels containing 0.5, 1 and 3 wt% MCNT exhibited
      slower trans-dermal release than neat CMG due to slightly higher gel viscosity
      and more drug entrapment. Slowest but steady release was obtained from 1 wt% MCNT
      loaded hydrogel due to highest viscous resistance among all other hybrid
      nanocomposites.

PMID- 21903132
TI  - A simple miniature device for wireless stimulation of neural circuits in small
      behaving animals.
AB  - The use of wireless neural stimulation devices offers significant advantages for
      neural stimulation experiments in behaving animals. We demonstrate a simple, low
      cost and extremely lightweight wireless neural stimulation device which is made
      from off-the-shelf components. The device has low power consumption and does not
      require a high-power RF preamplifier. Neural stimulation can be carried out in
      either a voltage source mode or a current source mode. Using the device, we carry
      out wireless stimulation in the premotor brain area HVC of a songbird and
      demonstrate that such stimulation causes rapid perturbations of the acoustic
      structure of the song.

PMID- 21903133
TI  - TLR-induced activation of neutrophils promotes histamine production via a PI3
      kinase dependent mechanism.
AB  - Histamine is a bioactive amine that exerts immunomodulatory functions, including
      many allergic symptoms. It is preformed and stored in mast cells and basophils
      but recent evidence suggests that other cell types produce histamine in an
      inducible fashion. During infection, it has been suggested that neutrophils may
      produce histamine. We also observed that histamine is released in a neutrophil
      mediated LPS-induced model of acute lung injury. Therefore, we sought to examine
      whether innate signals promote histamine production by neutrophils. Bone marrow
      derived neutrophils stimulated with a range of TLR agonists secreted histamine in
      response to LPS or R837, suggesting TLR4 or TLR7 are important. LPS-driven
      histamine was enhanced by coculture with GM-CSF and led to a transient release of
      histamine that peaked at 8h post stimulation. This was dependent upon de novo
      synthesis of histamine, since cells derived from histidine decarboxylase (HDC)
      deficient mice were unable to produce histamine but did generate reactive oxygen
      species upon stimulation. Using pharmacological inhibitors, we show that
      histamine production requires PI3 kinase, which has been shown to regulate other
      neutrophil functions, including activation and selective granule release.
      However, unlike mast cells, HDC deficiency did not alter the granule structure of
      neutrophils, suggesting that histamine does not participate in granule integrity
      in these cells. Consequently, our findings establish that neutrophils generate
      histamine in response to a select panel of innate immune triggers and that this
      might contribute to acute lung injury responses.

PMID- 21903134
TI  - Interleukin 28B genotype determination using DNA from different sources: A simple
      and reliable tool for the epidemiological and clinical characterization of
      hepatitis C.
AB  - Recent studies reported a close correlation between polymorphisms in the
      Interleukin (IL)28B gene and rates of resolution of hepatitis C virus infection
      occurring spontaneously or induced by treatment. The diagnostic utility of IL28B
      genotype, however, is not understood completely. For rapid data collection on the
      natural history of HCV infection in patients with different IL28B genotype,
      simple, sensitive and rapid methods suitable for non-invasive and archival
      clinical samples are needed urgently. A real-time polymerase chain reaction (PCR)
      method for IL28B typing (rs12979860) was developed using very small DNA
      quantities extracted from different biological specimens. Consistent IL28B
      genotyping of at least two DNA samples obtained from different sources such as
      whole blood, buccal swab, serum, and formalin fixed paraffin-embedded liver
      tissue was obtained from 58 patients with liver disease of mixed etiology. IL28B
      genotype prevalence in 170 patients with liver disease in this region of Italy
      was consistent with data reported in Caucasian populations. Differential
      distribution of genotypes was observed according to response to treatment in 68
      patients infected with HCV, with higher prevalence of CC genotype in responders
      (50%) compared to non-responders (17.85%; p=0.015). These results indicate that
      the possibility of reliable IL28B genotyping using different DNA sources may
      represent a useful tool for both clinical research and characterization of
      patients with hepatitis C.

PMID- 21903135
TI  - A multiplex calibrated real-time PCR assay for quantitation of DNA of EBV-1 and
      2.
AB  - Accurate and highly sensitive tests for the diagnosis of active Epstein-Barr
      virus (EBV) infection are essential for the clinical management of individuals
      infected with EBV. A calibrated quantitative real-time PCR assay for the
      measurement of EBV DNA of both EBV-1 and 2 subtypes was developed, combining the
      detection of the EBV DNA and a synthetic DNA calibrator in a multiplex PCR
      format. The assay displays a wide dynamic range and a high degree of accuracy
      even in the presence of 1MUg of human genomic DNA. This assay measures with the
      same efficiency EBV DNA from strains prevalent in different geographic areas. The
      clinical sensitivity and specificity of the system were evaluated by testing 181
      peripheral blood mononuclear cell (PBMCs) and plasma specimens obtained from 21
      patients subjected to bone marrow transplantation, 70 HIV-seropositive subjects
      and 23 healthy controls. Patients affected by EBV-associated post-transplant
      lymphoprolipherative disorders had the highest frequency of EBV detection and the
      highest viral load. Persons infected with HIV had higher levels of EBV DNA load
      in PBMCs and a higher frequency of EBV plasma viremia compared to healthy
      controls. In conclusion, this new assay provides a reliable high-throughput
      method for the quantitation of EBV DNA in clinical samples.

PMID- 21903136
TI  - Rapid detection of the most common high-risk human papillomaviruses by loop
      mediated isothermal amplification.
AB  - Persistent infection with high-risk human papillomavirus (HPV) is a major risk
      factor for development of cervical cancer. At present, polymerase chain reaction
      (PCR)-based methods, the most widely molecular tools used for HPV detection, are
      time-consuming and require expensive instruments. In this study, loop-mediated
      isothermal amplification (LAMP) was established for detection of HPV types 16,
      18, 45 and 58 which are frequently found in Thailand. The optimal condition for
      detection of these high risk HPVs was 63 degrees C for 60min. Since a white
      magnesium pyrophosphate precipitate is a characteristic by product of the LAMP
      reaction which can be visualized directly by the naked eye, the entire assay time
      of LAMP is 1h compared to 6-8h of for a nested PCR detection. The detection limit
      of LAMP assay was shown to be equivalent to nested PCR that could amplify 10(2)
      copies of HPV-18 and 10(3) copies of HPV 16, 45 and 58, as determined by either
      turbidity detection or agarose gel electrophoresis. No cross-reaction was
      observed, indicating that LAMP assay has high type-specificity. The assay showed
      successful detection of HPV in 56 clinical specimens. Using nested PCR as the
      gold standard, the sensitivity, specificity, negative predictive values and
      positive predictive values of LAMP assay were 100%. In conclusion, LAMP assay is
      a high efficiency, low cost diagnostic tool, useful for rapid, accurate, direct
      detection of HPV for clinical diagnosis.

PMID- 21903137
TI  - The periaqueductal gray as a critical site to mediate reward seeking during
      predatory hunting.
AB  - Previous studies using morphine-treated dams reported a role for the rostral
      lateral periaqueductal gray (rlPAG) in the behavioral switching between nursing
      and insect hunting, likely to depend on an enhanced seeking response to the
      presence of an appetitive rewarding cue (i.e., the roach). To elucidate the
      neural mechanisms mediating such responses, in the present study, we first
      observed how the rlPAG influences predatory hunting in male rats. Our behavioral
      observations indicated that bilateral rlPAG NMDA lesions dramatically interfere
      with prey hunting, leaving the animal without chasing or attacking the prey, but
      do not seem to affect the general levels of arousal, locomotor activity and
      regular feeding. Next, using Phaseolus vulgaris-leucoagglutinin (PHA-L), we have
      reviewed the rlPAG connection pattern, and pointed out a particularly dense
      projection to the hypothalamic orexinergic cell group. Double labeled PHA-L and
      orexin sections showed an extensive overlap between PHA-L labeled fibers and
      orexin cells, revealing that both the medial/perifornical and lateral
      hypothalamic orexinergic cell groups receive a substantial innervation from the
      rlPAG. We have further observed that both the medial/perifornical and lateral
      hypothalamic orexinergic cell groups up-regulate Fos expression during prey
      hunting, and that rlPAG lesions blunted this Fos increase only in the lateral
      hypothalamic, but not in the medial/perifornical, orexinergic group, a finding
      supposedly associated with the lack of motivational drive to actively pursue the
      prey. Overall, the present results suggest that the rlPAG should exert a critical
      influence on reward seeking by activating the lateral hypothalamic orexinergic
      cell group.

PMID- 21903138
TI  - Rapamycin protects against middle cerebral artery occlusion induced focal
      cerebral ischemia in rats.
AB  - Stroke is a major cause of mortality and disability. The management with
      thrombolytic therapy has to be initiated within 3-4 h and is associated with
      limitations like increased risk of intracranial hemorrhage and progression of
      cerebral injury. Immunophilin inhibitors such as cyclosporine A and tacrolimus
      have been shown to afford neuroprotection by improving neurological functions and
      infarct volume in models of ischemic stroke. In the present study, the effect of
      rapamycin in middle cerebral artery occlusion (MCAo) model of ischemic stroke was
      evaluated. Ischemic stroke was induced in rats by occluding the MCA using the
      intraluminal thread. After 1 h of MCAo, animals were administered rapamycin (50,
      150, 250 MUg/kg, i.p.). After 2 h of occlusion, reperfusion was done. Thirty
      minutes after reperfusion, animals were subjected to diffusion-weighted magnetic
      resonance imaging for assessment of protective effect of rapamycin. Twenty-four
      hours after MCAo, motor performance was assessed, the animals were euthanized and
      the brains were removed for estimation of malondialdehyde, glutathione, nitric
      oxide and myeloperoxidase. Significant improvement was observed with rapamycin
      150 and 250 MUg/kg in percent infarct area, apparent diffusion coefficient and
      signal intensity as compared to vehicle treated group. Rapamycin treatment
      ameliorated motor impairment associated with MCAo and significantly reversed the
      changes in levels of malondialdehyde, glutathione, nitric oxide and
      myeloperoxidase. The results of the present study indicate neuroprotective effect
      of rapamycin in MCAo model of stroke. Therefore, rapamycin might be considered as
      a therapeutic strategy for stroke management.

PMID- 21903139
TI  - Corin-deficient W-sh mice poorly tolerate increased cardiac afterload.
AB  - C57BL/6-Kit(W-sh/W-sh) mice are generally regarded as a mast cell-deficient
      model, as they lack the necessary kit receptor for mast cell development. Further
      characterization of this strain, however, indicates that C57BL/6-Kit(W-sh/W-sh)
      mice also have a disruption in the Corin gene. Corin is a transmembrane serine
      protease critical for processing atrial natriuretic peptide (ANP) from pro-ANP
      through proteolytic cleavage. Pro-ANP is produced, stored and released by cardiac
      myocytes in response to atrial stretch and the stress generated by increased
      afterload such as increased ventricular pressure from aortic stenosis or
      myocardial infarction. ANP inhibits the effects of the renin-angiotensin system
      to preserve homeostasis under conditions of increased hemodynamic load, and
      changes in the level of its activating enzyme Corin have been observed during the
      progression to heart failure. Here, we investigate the effect of increased
      hemodynamic load on Corin-deficient C57BL/6-Kit(W-sh/W-sh) mice. Ten-week old
      male mice were subjected to transverse aortic constriction for 8 weeks and were
      monitored for changes in cardiac structure and function by echocardiography.
      Hearts were collected 8 weeks after surgery for molecular and histological
      analyses. Corin-deficient C57BL/6-Kit(W-sh/W-sh) mice developed rapidly
      progressive and substantial left ventricular dilation, hypertrophy, and markedly
      impaired cardiac function during the 8 weeks after surgery, compared to wildtype
      mice. Concomitant with this we observed increased levels of ANP transcript, but a
      lack of prepro-ANP or pro-ANP protein in heart tissue extracted from Corin
      deficient mice. Surprisingly, fibrosis was not increased in Corin-deficient mice
      when compared to wildtype mice. These data indicate that Corin's involvement in
      ANP processing is a key element in the heart's response to increased hemodynamic
      load. Further, C57BL/6-Kit(W-sh/W-sh) strain is an effective model for
      investigating the involvement of Corin and, conversely, a less than optimal model
      for investigating mast cell, and immunological, functions in certain
      cardiovascular pathologies.

PMID- 21903131
TI  - G protein-coupled receptor kinases: more than just kinases and not only for
      GPCRs.
AB  - G protein-coupled receptor (GPCR) kinases (GRKs) are best known for their role in
      homologous desensitization of GPCRs. GRKs phosphorylate activated receptors and
      promote high affinity binding of arrestins, which precludes G protein coupling.
      GRKs have a multidomain structure, with the kinase domain inserted into a loop of
      a regulator of G protein signaling homology domain. Unlike many other kinases,
      GRKs do not need to be phosphorylated in their activation loop to achieve an
      activated state. Instead, they are directly activated by docking with active
      GPCRs. In this manner they are able to selectively phosphorylate Ser/Thr residues
      on only the activated form of the receptor, unlike related kinases such as
      protein kinase A. GRKs also phosphorylate a variety of non-GPCR substrates and
      regulate several signaling pathways via direct interactions with other proteins
      in a phosphorylation-independent manner. Multiple GRK subtypes are present in
      virtually every animal cell, with the highest expression levels found in neurons,
      with their extensive and complex signal regulation. Insufficient or excessive GRK
      activity was implicated in a variety of human disorders, ranging from heart
      failure to depression to Parkinson's disease. As key regulators of GPCR-dependent
      and -independent signaling pathways, GRKs are emerging drug targets and promising
      molecular tools for therapy. Targeted modulation of expression and/or of activity
      of several GRK isoforms for therapeutic purposes was recently validated in
      cardiac disorders and Parkinson's disease.

PMID- 21903140
TI  - Effect of dietary fatty acid composition on food intake, triglycerides, and
      hypothalamic peptides.
AB  - While a high-fat diet when compared to low-fat diet is known to produce
      overeating and health complications, less is known about the effects produced by
      fat-rich diets differing in their specific composition of fat. This study
      examined the effects of a high-fat diet containing relatively high levels of
      saturated compared to unsaturated fatty acids (HiSat) to a high-fat diet with
      higher levels of unsaturated fatty acids (USat). A HiSat compared to USat meal
      caused rats to consume more calories in a subsequent chow test meal. The HiSat
      meal also increased circulating levels of triglycerides (TG) and expression of
      the orexigenic peptides, galanin (GAL) in the hypothalamic paraventricular
      nucleus (PVN) and orexin (OX) in the perifornical lateral hypothalamus (PFLH). A
      similar increase in TG levels and PVN GAL and PFLH OX was also seen in rats given
      chronic access to the HiSat compared to USat diet, while neuropeptide Y (NPY) and
      agouti-related protein (AgRP) in the arcuate nucleus showed decreased expression.
      The importance of TG in producing these changes was supported by the finding that
      the TG-lowering medication gemfibrozil as compared to vehicle, when peripherally
      administered before consumption of a HiSat meal, significantly decreased the
      expression of OX, while increasing the expression of NPY and AgRP. These findings
      substantiate the importance of the fat composition in a diet, indicating that
      those rich in saturated compared to unsaturated fatty acids may promote
      overeating by increasing circulating lipids and specific hypothalamic peptides,
      GAL and OX, known to preferentially stimulate the consumption of a fat-rich diet.

PMID- 21903141
TI  - Pharmacologic antagonism of ghrelin receptors attenuates development of nicotine
      induced locomotor sensitization in rats.
AB  - AIMS: Ghrelin (GHR) is an orexigenic gut peptide that interacts with ghrelin
      receptors (GHR-Rs) to modulate brain reinforcement circuits. Systemic GHR
      infusions augment cocaine stimulated locomotion and conditioned place preference
      (CPP) in rats, whereas genetic or pharmacological ablation of GHR-Rs has been
      shown to attenuate the acute locomotor-enhancing effects of nicotine, cocaine,
      amphetamine and alcohol and to blunt the CPP induced by food, alcohol,
      amphetamine and cocaine in mice. The stimulant nicotine can induce CPP and like
      amphetamine and cocaine, repeated administration of nicotine induces locomotor
      sensitization in rats. A key issue is whether pharmacological antagonism of GHR
      Rs would similarly attenuate nicotine-induced locomotor sensitization. METHOD: To
      examine the role of GHR-Rs in the behavioral sensitizing effects of nicotine,
      adult male rats were injected with either 0, 3 or 6 mg/kg of the GHR-R receptor
      antagonist JMV 2959 (i.p.) and 20 min later with either vehicle or 0.4 mg/kg
      nicotine hydrogen tartrate (s.c.) on each of 7 consecutive days. RESULTS: Rats
      treated with nicotine alone showed robust locomotor sensitization, whereas rats
      pretreated with JMV 2959 showed significantly attenuated nicotine-induced
      hyperlocomotion. CONCLUSIONS: These results suggest that GHR-R activity is
      required for the induction of locomotor sensitization to nicotine and complement
      an emerging literature implicating central GHR systems in drug
      reward/reinforcement.

PMID- 21903142
TI  - Differential effects of activating D1 and D2 receptors on electrophysiology of
      neostriatal neurons in a rat model of Parkinson's disease induced by paraquat and
      maneb.
AB  - Neostriatum plays an important role in the pathophysiology of Parkinson's disease
      (PD). However, the changes of sensitivity of dopamine receptors of neostriatal
      neurons in PD have been less addressed in vivo. In the present study, systemic
      exposure to paraquat and maneb induced Parkinsonian symptoms and neuronal loss of
      substantia nigra pars compacta. Using single-unit recording methods, three types
      of neostriatal neurons were recorded including medium spiny-like neurons, large
      aspiny-like neurons and fast-spiking interneurons. In the exposed rats, increased
      firing activity of neostriatal neurons was revealed when compared to control
      rats. Following D1 receptor agonist, SKF38393 and D2 receptor agonist, LY171555
      iontophoretically administrated respectively, effects of increase and decrease in
      firing activity were both observed in neostriatal neurons. However, stronger
      inhibitory effects of activating D1 receptors and weaker excitatory effects of
      activating D2 receptors were found in the exposed rats as compared to controls.
      It indicated that differential changes of sensitivity of D1 and D2 receptors in
      Parkinson's disease were related to the modulation of the imbalance between D1
      receptor-dependent striatonigral direct pathway and D2-receptor-dependent
      striatopallidal indirect pathway. Our results illustrate the electrophysiological
      changes of in vivo neostriatal neurons in Parkinson's disease, thereby providing
      insight into the regulatory mechanisms of dopamine-mediated physiology.

PMID- 21903143
TI  - Oxidation of galactomannan by laccase plus TEMPO yields an elastic gel.
AB  - Chemical modifications of galactomannans are applied to improve and/or modify
      their solubility, rheological and functional properties, but have limited
      specificity and are often difficult to control. Enzymatic reactions, catalyzed
      under mild process conditions, such as depolymerization, debranching and
      oxidation, represent a viable and eco-friendly alternative. In this study, we
      describe oxidation of guar galactomannan primary hydroxyl groups by a fungal
      laccase using the stable radical TEMPO as mediator. Four fungal laccases were
      investigated from: Trametes versicolor, Myceliophthora thermophila, Thielavia
      arenaria, Cerrena unicolor. The laccase from T. versicolor was found to
      efficiently oxidize TEMPO and to be free of mannanase side activity. Oxidation of
      galactomannan with this enzyme plus TEMPO brought about a ten-fold increase in
      viscosity of a guar galactomannan solution and altered its rheological profile,
      by converting a viscous polysaccharide solution into an elastic gel. This
      structural modification is presumably due to formation of inter-chain
      hemiacetalic bonds between newly generated carbonyl groups and free OH groups,
      yielding a cross-linked gel. These findings could be of practical importance,
      considering that polysaccharides with high viscosity, gelling and elastic
      properties can find interesting and novel applications as thickeners,
      viscosifiers and emulsion stabilizers in several industrial applications such as:
      personal care, oil operations, paper coating, paints, construction and mining.

PMID- 21903144
TI  - Analysis and prediction of the physiological effects of altered coenzyme
      specificity in xylose reductase and xylitol dehydrogenase during xylose
      fermentation by Saccharomyces cerevisiae.
AB  - An advanced strategy of Saccharomyces cerevisiae strain development for
      fermentation of xylose applies tailored enzymes in the process of metabolic
      engineering. The coenzyme specificities of the NADPH-preferring xylose reductase
      (XR) and the NAD+-dependent xylitol dehydrogenase (XDH) have been targeted in
      previous studies by protein design or evolution with the aim of improving the
      recycling of NADH or NADPH in their two-step pathway, converting xylose to
      xylulose. Yeast strains expressing variant pairs of XR and XDH that according to
      in vitro kinetic data were suggested to be much better matched in coenzyme usage
      than the corresponding pair of wild-type enzymes, exhibit widely varying
      capabilities for xylose fermentation. To achieve coherence between enzyme
      properties and the observed strain performance during fermentation, we explored
      the published kinetic parameters for wild-type and engineered forms of XR and XDH
      as possible predictors of xylitol by-product formation (Y(xylitol)) in yeast
      physiology. We found that the ratio of enzymatic reaction rates using NADP(H) and
      NAD(H) that was calculated by applying intracellular reactant concentrations to
      rate equations derived from bi-substrate kinetic analysis, succeeded in giving a
      statistically reliable forecast of the trend effect on Y(xylitol). Prediction
      based solely on catalytic efficiencies with or without binding affinities for
      NADP(H) and NAD(H) were not dependable, and we define a minimum demand on the
      enzyme kinetic characterization to be performed for this purpose. An immediate
      explanation is provided for the typically lower Y(xylitol) in the current strains
      harboring XR engineered for utilization of NADH as compared to strains harboring
      XDH engineered for utilization of NADP+. The known XDH enzymes all exhibit a
      relatively high K(m) for NADP+ so that physiological boundary conditions are
      somewhat unfavorable for xylitol oxidation by NADP+. A criterion of physiological
      fitness is developed for engineered XR working together with wild-type XDH.

PMID- 21903146
TI  - PEG-stabilized lipid disks as carriers for amphiphilic antimicrobial peptides.
AB  - Antimicrobial peptides hold potential as a possible alternative, or complement,
      to conventional antibiotics but new, safe and efficient means are needed for
      formulation and administration of the peptides. In this study we have
      investigated the utility of a novel type of lipid particles, the polyethylene
      glycol-stabilized lipid disks, as carriers for the model peptide melittin. The
      structural integrity of the carrier particle when loaded with the peptide was
      investigated using cryo-transmission electron microscopy. Liposome leakage upon
      addition of the peptide-lipid disks was monitored as a means to verify the
      membrane lytic effect of the formulation. The susceptibility of melittin to
      tryptic digestion was studied and compared in the absence and presence of lipid
      disks. Finally, the antibacterial effect of the peptide-lipid disk formulation
      was compared to that of free melittin after both single and repeated exposure to
      Escherichia coli. The results show that melittin can redistribute from the disk
      into a new host membrane and that formulation in the disks does not compromise
      melittin's membrane permeabilizing ability. Further, the peptide was found to be
      fully protected against degradation when bound to the disks. Time-kill
      experiments revealed that all the antibacterial effect of melittin administered
      in free form was gone after a single exposure to E. coli. In contrast, the disk
      formulation showed significant cell-killing effect also upon a second exposure to
      bacteria, indicating an extended release of peptide from the lipid disks. These
      results suggest that the lipid disks constitute a new class of promising carriers
      for peptide antibiotics.

PMID- 21903145
TI  - Highly compacted DNA nanoparticles with low MW PEG coatings: in vitro, ex vivo
      and in vivo evaluation.
AB  - Highly compacted DNA nanoparticles, composed of single molecules of plasmid DNA
      compacted with block copolymers of poly-l-lysine and 10kDa polyethylene glycol
      (CK(30)PEG(10k)), mediate effective gene delivery to the brain, eyes and lungs in
      vivo. Nevertheless, we found that CK(30)PEG(10k) DNA nanoparticles are
      immobilized by mucoadhesive interactions in sputum that lines the lung airways of
      patients with cystic fibrosis (CF), which would presumably preclude the efficient
      delivery of cargo DNA to the underlying epithelium. We previously found that
      nanoparticles can rapidly penetrate human mucus secretions if they are densely
      coated with low MW PEG (2-5kDa), whereas nanoparticles with 10kDa PEG coatings
      were immobilized. We thus sought to reduce mucoadhesion of DNA nanoparticles by
      producing CK(30)PEG DNA nanoparticles with low MW PEG coatings. We examined the
      morphology, colloidal stability, nuclease resistance, diffusion in human sputum
      and in vivo gene transfer of CK(30)PEG DNA nanoparticles prepared using various
      PEG MWs. CK(30)PEG(10k) and CK(30)PEG(5k) formulations did not aggregate in
      saline, provided partial protection against DNase I digestion and exhibited the
      highest gene transfer to lung airways following inhalation in BALB/c mice.
      However, all DNA nanoparticle formulations were immobilized in freshly
      expectorated human CF sputum, likely due to inadequate PEG surface coverage.

PMID- 21903147
TI  - Oxytocin in the rat caudate nucleus influences pain modulation.
AB  - Our previous studies have demonstrated that oxytocin (OXT) in the central nervous
      system plays a role in pain modulation. Many studies have found that caudate
      nucleus (CdN) enriches OXT and OXT receptors by the methods of
      historadioautograph and gene expression. The communication was designed to
      investigate OXT effect in the rat CdN on pain modulation. The results showed that
      (1) intra-CdN microinjection of OXT receptor antagonist, desGly-NH(2),
      d(CH(2))(5)[D-Tyr(2), Thr-sup-4]OVT decreased the pain threshold, whereas the
      local administration of OXT increased the pain threshold in a dose-dependent
      manner; (2) OXT receptor antagonist can attenuate the analgesic role induced
      intra-CdN administration of OXT; and (3) pain stimulation could increase OXT
      concentration in the CdN perfusion liquid. The data suggested that OXT in the CdN
      was involved in this pain process via OXT receptors.

PMID- 21903149
TI  - The truncated ghrelin receptor polypeptide (GHS-R1b) is localized in the
      endoplasmic reticulum where it forms heterodimers with ghrelin receptors (GHS
      R1a) to attenuate their cell surface expression.
AB  - The ghrelin receptor (GHS-R1a) is remarkable amongst G-protein-coupled receptors
      for its high degree of constitutive activity, and this agonist-independent
      activity may be important for its physiological function in the control of food
      intake and body weight. Ghrelin receptors form heterodimers with the truncated
      ghrelin receptor polypeptide (GHS-R1b), which has a dominant-negative effect on
      ghrelin receptor function. Here we show that GHS-R1b has an intracellular
      localization distinct from ghrelin receptors, being primarily localized in the
      endoplasmic reticulum. Immunocytochemical studies suggest that GHS-R1b decreases
      the plasma membrane expression of ghrelin receptors, but the overall distribution
      profile of ghrelin receptors in isolated subcellular fractions is unaffected by
      GHS-R1b. Using bioluminescence resonance energy transfer methods, we have shown
      that while ghrelin receptor homodimers are evenly distributed in all subcellular
      fractions, GHS-R1a/GHS-R1b heterodimers are concentrated within the endoplasmic
      reticulum and these results suggest that GHS-R1b traps ghrelin receptors within
      the endoplasmic reticulum by the process of oligomerization. Furthermore, ghrelin
      receptors constitutively activated extracellular signal-regulated kinases 1/2 in
      the endoplasmic reticulum, but this small response was not affected by GHS-R1b
      and its physiological relevance is uncertain. Taken together, these results
      suggest that ghrelin receptors can be retained in the endoplasmic reticulum by
      heterodimerization with GHS-R1b, and constitutive activation of phospholipase C
      is attenuated due to decreased cell surface expression of ghrelin receptors.
      However, sufficient ghrelin receptor homodimers can still be expressed on the
      cell surface for maximal responses to agonist stimulation.

PMID- 21903150
TI  - Polymorphisms in LMNA and near a SERPINA13 gene are not associated with cognitive
      performance in Chinese elderly males without dementia.
AB  - Aging is associated with cognitive deterioration. A recent study showed two
      polymorphisms (rs505058 in LMNA and rs11622883 near a SERPINA13 gene), identified
      in a genome-wide association study of late-onset Alzheimer's disease, to be
      associated with cognitive function (Mini Mental State Examination) in a UK
      elderly population. This study replicated these findings in Chinese elderly males
      without dementia. A total of 358 elderly subjects were assessed by the Cognitive
      Abilities Screening Instruments (CASI) and the Wechsler Digit Span Task tests.
      Analysis of covariance was used to compare cognitive scores among genotypic
      groups, with age and total education years as covariates. The two polymorphisms
      were not associated with the global cognitive function or specific cognitive
      domains in the elderly without dementia. Our data argue against that these two
      polymorphisms may affect cognitive function in the elderly.

PMID- 21903151
TI  - Increased apoptosis and different regulation of pro-apoptosis protein bax and
      anti-apoptosis protein bcl-2 in the olfactory bulb of a rat model of depression.
AB  - Reduced olfactory bulb (OB) volume and olfactory sensitivity have been observed
      in depressed patients, the exact mechanisms underlying, however, are still
      unknown. Our previous study found that decreased neurogenesis and pre-synaptic
      dysfunction in the OB of a rat model of depression may be responsible for the
      phenomena. Nevertheless, whether the apoptosis would also play a certain role in
      this process is not clear. In this study, we investigated the apoptosis in the OB
      of a chronic unpredictable mild stress (CUMS) rat model of depression using
      terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)
      staining. Simultaneously, the pro-apoptosis protein bax and anti-apoptosis
      protein bcl-2 were detected by Western blot. The results showed that the number
      of TUNEL-positive cells increased dramatically in the glomerular layer of the OB
      of the CUMS rats, accompanied with up-regulated expression of bax protein and
      down-regulated expression of bcl-2 protein. The findings indicate that increased
      apoptosis may be attributed to explain at some level for the reduced OB volume
      and olfactory dysfunction in depressed patients. Moreover, the mitochondria
      dependent death pathway might be involved in apoptosis in the OB of the CUMS
      rats.

PMID- 21903148
TI  - The great migration of bone marrow-derived stem cells toward the ischemic brain:
      therapeutic implications for stroke and other neurological disorders.
AB  - Accumulating laboratory studies have implicated the mobilization of bone marrow
      (BM)-derived stem cells in brain plasticity and stroke therapy. This mobilization
      of bone cells to the brain is an essential concept in regenerative medicine. Over
      the past ten years, mounting data have shown the ability of bone marrow-derived
      stem cells to mobilize from BM to the peripheral blood (PB) and eventually enter
      the injured brain. This homing action is exemplified in BM stem cell mobilization
      following ischemic brain injury. Various BM-derived cells, such as hematopoietic
      stem cells (HSCs), mesenchymal stem cells (MSCs), endothelial progenitor cells
      (EPCs) and very small embryonic-like cells (VSELs) have been demonstrated to
      exert therapeutic benefits in stroke. Here, we discuss the current status of
      these BM-derived stem cells in stroke therapy, with emphasis on possible cellular
      and molecular mechanisms of action that mediate the cells' beneficial effects in
      the ischemic brain. When possible, we also discuss the relevance of this
      therapeutic regimen in other central nervous system (CNS) disorders.

PMID- 21903152
TI  - Expression of cocaine- and amphetamine-regulated transcript in the rat forebrain
      during postnatal development.
AB  - Cocaine- and amphetamine-regulated transcript (CART) is widespread in the rodent
      brain. CART has been implicated in many different functions including reward,
      feeding, stress responses, sensory processing, learning and memory formation.
      Recent studies have suggested that CART may also play a role in neural
      development. Therefore, in the present study we compared the distribution pattern
      and levels of CART mRNA expression in the forebrain of male and female rats at
      different stages of postnatal development: P06, P26 and P66. At 6 days of age
      (P06), male and female rats showed increased CART expression in the somatosensory
      and piriform cortices, indusium griseum, dentate gyrus, nucleus accumbens, and
      ventral premammillary nucleus. Interestingly, we found a striking expression of
      CART mRNA in the ventral posteromedial and ventral posterolateral thalamic
      nuclei. This thalamic expression was absent at P26 and P66. Contrastingly, at P06
      CART mRNA expression was decreased in the arcuate nucleus. Comparing sexes, we
      found increased CART mRNA expression in the anteroventral periventricular nucleus
      of adult females. In other regions including the CA1, the lateral hypothalamic
      area and the dorsomedial nucleus of the hypothalamus, CART expression was not
      different comparing postnatal ages and sexes. Our findings indicate that CART
      gene expression is induced in a distinct temporal and spatial manner in forebrain
      sites of male and female rats. They also suggest that CART peptide participate in
      the development of neural pathways related to selective functions including
      sensory processing, reward and memory formation.

PMID- 21903153
TI  - In vitro anti-uveal melanoma activity of phenolic compounds from the Egyptian
      medicinal plant Acacia nilotica.
AB  - Anti-uveal melanoma activity-guided fractionation of the MeOH extract of Acacia
      nilotica pods resulted in the isolation of the new compound gallocatechin 5-O
      gallate in addition to methyl gallate, gallic acid, catechin, catechin 5-O
      gallate, 1-O-galloyl-beta-D-glucose, 1,6-di-O-galloyl-beta-D-glucose and digallic
      acid. The structures of the isolated compounds were elucidated on the basis of
      HRESIMS, NMR spectroscopy and CD data. In addition to uveal melanoma, the
      antiproliferative activities of the isolated compounds and the related compound
      epigallocatechin 3-O-gallate (EGCG) were evaluated against cutaneous melanoma,
      ovarian cancer, glioblastoma and normal retinal pigmented cells.

PMID- 21903154
TI  - Integration of biological monitoring, environmental monitoring and computational
      modelling into the interpretation of pesticide exposure data: introduction to a
      proposed approach.
AB  - Open field, variability of climatic and working conditions, and the use of
      complex mixtures of pesticides makes biological and environmental monitoring in
      agriculture, and therefore risk assessment and management, very complicated. A
      need of pointing out alternative risk assessment approaches, not necessarily
      based on measures, but simple, user-friendly and reliable, feasible also in the
      less advanced situations and in particular in small size enterprises, arises.
      This aim can be reached through a combination of environmental monitoring,
      biological monitoring and computational modelling. We have used this combination
      of methods for the creation of "exposure and risk profiles" to be applied in
      specific exposure scenarios, and we have tested this approach on a sample of
      Italian rice and maize herbicide applicators. We have given specific "toxicity
      scores" to the different products used and we have identified, for each of the
      major working phases, that is mixing and loading, spraying, maintenance and
      cleaning of equipment, the main variables affecting exposure and inserted them
      into a simple algorithm, able to produce "exposure indices". Based on the
      combination of toxicity indices and exposure indices it is possible to obtain
      semiquantitative estimates of the risk levels experienced by the workers in the
      exposure scenarios considered. Results of operator exposure data collected under
      real-life conditions can be used to validate and refine the algorithms; moreover,
      the AOEL derived from pre-marketing studies can be combined to estimate tentative
      biological exposure limits for pesticides, useful to perform individual risk
      assessment based on technical surveys and on simple biological monitoring. A
      proof of principle example of this approach is the subject of this article.

PMID- 21903155
TI  - Application of headspace solid phase dynamic extraction gas chromatography/mass
      spectrometry (HS-SPDE-GC/MS) for biomonitoring of n-heptane and its metabolites
      in blood.
AB  - Solid phase dynamic extraction (SPDE) is an innovative sample preparation and
      enrichment technique in connection with gas chromatography (GC). Using SPDE, we
      developed a method for simultaneous determination of n-heptane and its mono
      oxygenated metabolites heptane-4-one, 3-one, 2-one, 4-ol, 3-ol, 2-ol, and 1-ol in
      blood. After adjustment of various extraction and desorption parameters, method
      validation resulted in limits of detection (LOD) between 0.006 (heptane-4-one)
      and 0.021mg/L (heptane-1-ol). Intra-assay coefficients of variation ranged
      between 4.8% and 20.8% while relative recovery ranged between 100% and 117%
      (spiked concentration 0.128mg/L, n=8). The method was applied to blood samples,
      which have been collected from 20 volunteers after controlled inhalative exposure
      to 167, 333, and 500ppm n-heptane. After 3h of exposure, n-heptane and heptane-2
      one were detectable in all samples in concentrations ranging up to 2.903 and
      0.495mg/L, while the concentrations of the remaining analytes were closer to the
      respective LOD or even below. A significant linear relationship with ambient
      exposure (R(2)=0.701, p<0.001, n=55) was found for n-heptane in blood, which
      could be helpful for evaluation of biological exposure limits in future. Due to
      its high abundance in blood, 2-heptanone could be an interesting candidate as a
      biomarker also in alternative matrices such as urine or saliva.

PMID- 21903156
TI  - Inhibition of the p38 and PKA signaling pathways is associated with the anti
      melanogenic activity of Qian-wang-hong-bai-san, a Chinese herbal formula, in B16
      cells.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Qian-wang-hong-bai-san (QW), a Chinese herbal
      formula, is traditionally used as a skin whitening agent in China. AIM OF STUDY:
      In our previous screening assays, QW was identified as an effective tyrosinase
      inhibitor. In this study, we aim to investigate the underlying mechanism of the
      anti-melanogenic effect of QW in B16 cells. MATERIALS AND METHODS: Cytotoxicity
      of QW in B16 cell line was examined by MTT assay. Cellular tyrosinase activity
      was determined based on the melanin content measured at 475 nm with a microplate
      spectrophotometer. Protein expression was analyzed by Western blotting and
      quantified by Quantity One. RESULTS: QW dose-dependently inhibited tyrosinase
      activity and decreased melanin content at 48 h without significant cytotoxicity
      in B16 cells. Western blot analysis showed that QW treatment down-regulated the
      expression levels of phospho-p38, phospho-CREB, MITF, tyrosinase, TRP-1 and TRP-2
      in a dose-dependent manner. At the same time, QW treatment for 48 h inhibited
      IBMX-induced elevation of cellular melanin content and tyrosinase activity.
      However, the attenuation of IBMX-mediated up-regulations of phospho-CREB and
      phospho-PKA was readily observed with 60 min of QW treatment. CONCLUSIONS: The
      anti-melanogenic activity of QW in B16 melanoma cells can be attributed, at least
      in part, to the inhibition of the p38 MAPK and PKA signaling pathways. These
      findings shed new light on the molecular mechanisms of the skin-whitening
      property of QW.

PMID- 21903158
TI  - ZnO nanoparticles induce apoptosis in human dermal fibroblasts via p53 and p38
      pathways.
AB  - The production of engineered nanoparticles is growing rapidly as the field of
      nanotechnology continues to expand. Zinc oxide nanoparticles (ZnO NPs) are used
      in various applications, including catalysis, electronics, biosensors, medicine,
      paints, sunscreens and cosmetics, thus it is important to understand the
      biological effects and risks of ZnO NPs. This study was designed to investigate
      the apoptosis induction by ZnO NPs via mitogen-activated protein kinase p38 and
      cell cycle checkpoint protein p53 pathways in human dermal fibroblasts. MTT-based
      cell viability assay showed a significant decrease in cell survivorship after ZnO
      NP exposure, and phase contrast images revealed that ZnO NP treated cells had
      lower density and a rounded morphology. Apoptosis induction was confirmed by the
      annexin V assay and Western blot analysis showed the up-regulation of p53 and
      phospho-p38 proteins. Furthermore, in ZnO NP exposed cells, p53 protein was
      phosphorylated at Ser33 and Ser46 sites known to be phosphorylated by p38. Our
      results suggest that ZnO NPs have the potential to induce apoptosis in human
      dermal fibroblasts via p53-p38 pathways.

PMID- 21903157
TI  - Proteomic studies on protective effects of salvianolic acids, notoginsengnosides
      and combination of salvianolic acids and notoginsengnosides against cardiac
      ischemic-reperfusion injury.
AB  - ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza and Panax notoginseng are
      popularly used traditional Chinese medicine for cardiovascular disorders and they
      are often used in the form of combination. However, mechanisms of their
      cardioprotective effects were still not clear. In the present study, the
      protective effects of salvianolic acids (SA), notoginsengnosides (NG) and
      combination of SA and NG (CSN) against rat cardiac ischemia-reperfusion injury
      were checked and the protein expression profiles of heart tissues were examined
      to search their possible protein targets. MATERIALS AND METHODS: The
      cardioprotective effects of SA, NG and CSN were checked in a rat model of
      ischemia-reperfusion (IR) by temporarily occluding coronary artery for 20 min
      followed by reperfusion. Rats were grouped into sham-operation group, IR group,
      IR+SA group, IR+NG group and IR+CSN group. The plasma creatine kinase (CK)
      activities were measured using commercial kit and the percentages of infarcted
      area in total ventricle tissue were calculated after nitroblue-tetrazolium (N-BT)
      staining of heart tissue slices. Two-dimensional protein electrophoresis (2-DE)
      was used to check the protein expression profiles of heart tissues. Then,
      proteins differentially expressed between IR group and sham-operation group were
      identified using matrix assisted laser desorption ionization-time of flight-mass
      spectrometry/mass spectrometry (MALDI-TOF MS/MS). The regulative effects of SA,
      NG and CSN on these IR-related proteins were analyzed. RESULTS: Treatments
      including SA, NG and CSN all showed cardioprotective effects against ischemia
      reperfusion injury and CSN exhibited to be the best. Eighteen proteins involved
      in IR injury were found. These proteins are involved in pathways including energy
      metabolism, lipid metabolism, muscle contraction, heat shock stress, cell
      survival and proliferation. The regulation of these proteins by SA, NG or CSN
      suggested possible protein targets in their cardioprotective effects.
      CONCLUSIONS: SA and NG showed both similarity and difference in their protein
      targets involved in cardioprotective effects. The capability of CSN to regulate
      both protein targets of SA and NG might be the basis of CSN to show
      cardioprotective effects better than that of SA or NG.

PMID- 21903160
TI  - The transfer of 6-mercaptopurine in the dually perfused human placenta.
AB  - The immunosuppressant azathioprine is increasingly being used in pregnancy. The
      human placenta is considered a relative barrier to the major metabolite, 6
      mercaptopurine (6-MP), and likely explains the lack of proven teratogenicity in
      humans. The aim of this study was to determine how the human placenta restricts 6
      MP transfer using the human placental perfusion model. After addition of 50 ng/ml
      (n=4) and 500 ng/ml (n=3) 6-MP into the maternal circulation, there was a
      biphasic decline in its concentration and a delay in fetal circulation
      appearance. Under equilibrative conditions, the fetal-to-maternal concentration
      ratio was >1.0 as a result of ion trapping. Binding to placental tissue and
      maternal pharmacokinetic parameters are the main factors that restrict placental
      transfer of 6-MP. Active transport is unlikely to play a significant role and
      drug interactions involving, or polymorphisms in, placental drug efflux
      transporters are not likely to put the fetus at risk of higher 6-MP exposure.

PMID- 21903159
TI  - Design and coverage of high throughput genotyping arrays optimized for
      individuals of East Asian, African American, and Latino race/ethnicity using
      imputation and a novel hybrid SNP selection algorithm.
AB  - Four custom Axiom genotyping arrays were designed for a genome-wide association
      (GWA) study of 100,000 participants from the Kaiser Permanente Research Program
      on Genes, Environment and Health. The array optimized for individuals of European
      race/ethnicity was previously described. Here we detail the development of three
      additional microarrays optimized for individuals of East Asian, African American,
      and Latino race/ethnicity. For these arrays, we decreased redundancy of high
      performing SNPs to increase SNP capacity. The East Asian array was designed using
      greedy pairwise SNP selection. However, removing SNPs from the target set based
      on imputation coverage is more efficient than pairwise tagging. Therefore, we
      developed a novel hybrid SNP selection method for the African American and Latino
      arrays utilizing rounds of greedy pairwise SNP selection, followed by removal
      from the target set of SNPs covered by imputation. The arrays provide excellent
      genome-wide coverage and are valuable additions for large-scale GWA studies.

PMID- 21903161
TI  - Localization and neurochemical characteristics of the extrinsic sympathetic
      neurons projecting to the pylorus in the domestic pig.
AB  - The pylorus, an important part of the digestive tract controlling the flow of
      chyme between the stomach and the duodenum, is widely innervated by intrinsic and
      extrinsic nerves. To determine the locations of postganglionic sympathetic
      perikarya that innervate the pylorus of the domestic pig, a retrograde tracing
      method with application of Fast Blue tracer was used. All positive neuronal cell
      bodies (ca. 1750) were found in the celiac-cranial mesenteric ganglion complex
      (CSMG), however, the coeliac poles of this complex provided the major input to
      the pylorus. Afterwards, the immunohistochemical staining procedure was applied
      to determine biologically active substances expressed in the FB-labeled
      perikarya. Approximately 77% of the FB-positive cell bodies contained tyrosine
      hydroxylase (TH), 87% dopamine beta-hydroxylase (DbetaH), 40% neuropeptide Y
      (NPY), 12% somatostatin (SOM) and 7% galanin (GAL). The presence of all these
      substances in the ganglion tissue was confirmed by RT-PCR technique. Double
      immunocytochemistry revealed that all of the TH-positive perikarya contained
      DbetaH, about 40% NPY, 12% SOM and 8% GAL. Additionally, all above-cited
      immunohistochemical markers as well as VIP, PACAP, ChAT, LEU, MET, SP and nNOS
      were observed within nerve fibers associated with the FB-positive perikarya.
      Immunocytochemical labeling of the pyloric wall tissue disclosed that TH+,
      DbetaH+ and NPY+ nerve fibers innervated ganglia of the myenteric and submucosal
      plexuses, blood vessels, both muscular layers and the muscularis mucosae; nerve
      fibers immunoreactive to GAL mostly innervated both muscular layers, while SOM+
      nerve fibers were observed within the myenteric plexus. Presented study revealed
      sources of origin and immunohistochemical characteristics of the sympathetic
      postganglionic perikarya innervating the porcine pylorus.

PMID- 21903162
TI  - In vivo imaging and quantitative analysis of changes in axon length using
      transgenic zebrafish embryos.
AB  - We describe an imaging procedure to measure axon length in zebrafish embryos in
      vivo. Automated fluorescent image acquisition was performed with the ImageXpress
      Micro high content screening reader and further analysis of axon lengths was
      performed on archived images using AcuityXpress software. We utilized the Neurite
      Outgrowth Application module with a customized protocol (journal) to measure the
      axons. Since higher doses of ethanol (2-2.5%, v/v) have been shown to deform
      motor neurons and axons during development, here we used ethanol to treat
      transgenic [hb9:GFP (green fluorescent protein)] zebrafish embryos at 28 hpf
      (hours post-fertilization). These embryos express GFP in the motor neurons and
      their axons. Embryos after ethanol treatment were arrayed in 384-well plates for
      automated fluorescent image acquisition in vivo. Average axon lengths of high
      dose ethanol-treated embryos were significantly lower than the control. Another
      experiment showed that there was no significant difference in the axon lengths
      between the embryos grown for 24h at 22 degrees C and 28.5 degrees C. These test
      experiments demonstrate that using axon development as an end-point, compound
      screening can be performed in a time-efficient manner.

PMID- 21903163
TI  - Modelling formulations using gene expression programming--a comparative analysis
      with artificial neural networks.
AB  - This study has investigated the utility and potential advantages of gene
      expression programming (GEP)--a new development in evolutionary computing for
      modelling data and automatically generating equations that describe the cause-and
      effect relationships in a system--to four types of pharmaceutical formulation and
      compared the models with those generated by neural networks, a technique now
      widely used in the formulation development. Both methods were capable of
      discovering subtle and non-linear relationships within the data, with no
      requirement from the user to specify the functional forms that should be used.
      Although the neural networks rapidly developed models with higher values for the
      ANOVA R(2) these were black box and provided little insight into the key
      relationships. However, GEP, although significantly slower at developing models,
      generated relatively simple equations describing the relationships that could be
      interpreted directly. The results indicate that GEP can be considered an
      effective and efficient modelling technique for formulation data.

PMID- 21903164
TI  - Neurofibromatosis-1 heterozygosity impairs CNS neuronal morphology in a
      cAMP/PKA/ROCK-dependent manner.
AB  - Children with the neurofibromatosis-1 (NF1) cancer predisposition syndrome
      exhibit numerous clinical problems that reflect defective central nervous system
      (CNS) neuronal function, including learning disabilities, attention deficit
      disorder, and seizures. These clinical features result from reduced NF1 protein
      (neurofibromin) expression in NF1+/- (NF1 heterozygosity) brain neurons. Previous
      studies have shown that mouse CNS neurons are sensitive to the effects of reduced
      Nf1 expression and exhibit shorter neurite lengths, smaller growth cone areas,
      and attenuated survival, reflecting attenuated neurofibromin cAMP regulation. In
      striking contrast, Nf1+/- peripheral nervous system (PNS) neurons are nearly
      indistinguishable from their wild-type counterparts, and complete neurofibromin
      loss leads to increased neurite lengths and survival in a RAS/Akt-dependent
      fashion. To gain insights into the differential responses of CNS and PNS neurons
      to reduced neurofibromin function, we designed a series of experiments to define
      the molecular mechanism(s) underlying the unique CNS neuronal sensitivity to Nf1
      heterozygosity. First, Nf1 heterozygosity decreases cAMP levels in CNS, but not
      in PNS, neurons. Second, CNS neurons exhibit Nf1 gene-dependent increases in RAS
      pathway signaling, but no further decreases in cAMP levels were observed in Nf1-/
      CNS neurons relative to their Nf1+/- counterparts. Third, neurofibromin
      regulates CNS neurite length and growth cone areas in a cAMP/PKA/Rho/ROCK
      dependent manner in vitro and in vivo. Collectively, these findings establish
      cAMP/PKA/Rho/ROCK signaling as the responsible axis underlying abnormal Nf1+/-
      CNS neuronal morphology with important implications for future preclinical and
      clinical studies aimed at improving cognitive and behavioral deficits in mice and
      children with reduced brain neuronal NF1 gene expression.

PMID- 21903165
TI  - In vitro and intrathecal siRNA mediated K(V)1.1 knock-down in primary sensory
      neurons.
AB  - K(V)1.1 is a Shaker homologue K(+) channel that contributes to the juxta
      paranodal membrane conductance in myelinated axons, and is blocked by fampridine
      (4-aminopyridine), used to treat the symptoms of multiple sclerosis. The present
      experiments investigate K(V)1.1 function in primary sensory neurons and A-fibres,
      and help define its characteristics as a drug-target using sequence specific
      small-interfering RNAs (siRNAs). siRNA (71nM) was used to knock-down functional
      expression of K(V)1.1 in sensory neurons (>25MUm in apparent diameter) in
      culture, and was also delivered intrathecally in vivo (9.3MUg). K(+) channel
      knock-down in sensory neurons was found to make the voltage-threshold for action
      potential generation significantly more negative than in control (p=0.02), led to
      the breakdown of accommodation and promoted spontaneous action potential firing.
      Exposure to dendrotoxin-K (DTX-K, 10-100nM) also selectively abolished K(+)
      currents at negative potentials and made voltage-threshold more negative,
      consistent with K(V)1.1 controlling excitability close to the nominal resting
      potential of the neuron cell body, near -60mV. Introduction of one working siRNA
      sequence into the intrathecal space in vivo was associated with a small increase
      in the amplitude of the depolarising after-potential in sacral spinal roots
      (p<0.02), suggesting a reduction in the number of working K(+) channels in
      internodal axon membrane. Our study provides evidence that K(V)1.1 contributes to
      the control of peripheral sensory nerve excitability, and suggests that its
      characteristics as a putative drug target can be assessed by siRNA transfection
      in primary sensory neurons in vitro and in vivo.

PMID- 21903166
TI  - Characterization of lipid matrices for membrane protein crystallization by high
      throughput small angle X-ray scattering.
AB  - The lipidic cubic phase (LCP) has repeatedly proven to serve as a successful
      membrane-mimetic matrix for a variety of difficult-to-crystallize membrane
      proteins. While monoolein has been the predominant lipid of choice, there is a
      growing need for the characterization and use of other LCP host lipids, allowing
      exploration of a range of structural parameters such as bilayer thickness and
      curvature for optimal insertion, stability and crystallogenesis of membrane
      proteins. Here, we describe the development of a high-throughput (HT) pipeline to
      employ small angle X-ray scattering (SAXS) - the most direct technique to
      identify lipid mesophases and measure their structural parameters - to
      interrogate rapidly a large number of lipid samples under a variety of
      conditions, similar to those encountered during crystallization. Leveraging the
      identical setup format for LCP crystallization trials, this method allows the
      quickly assessment of lipid matrices for their utility in membrane protein
      crystallization, and could inform the tailoring of lipid and precipitant
      conditions to overcome specific crystallization challenges. As proof of concept,
      we present HT LCP-SAXS analysis of lipid samples made of monoolein with and
      without cholesterol, and of monovaccenin, equilibrated with solutions used for
      crystallization trials and LCP fluorescence recovery after photobleaching (FRAP)
      experiments.

PMID- 21903167
TI  - Production of the stable human histamine H1 receptor in Pichia pastoris for
      structural determination.
AB  - G-protein coupled receptors (GPCRs) play essential roles in regulation of many
      physiological processes and are one of the major targets of pharmaceutical drugs.
      The 3D structure can provide important information for the understanding of GPCR
      function and the design of new drugs. However, the success of structure
      determination relies largely on the production of recombinant GPCRs, because the
      expression levels of GPCRs are very low in native tissues except rhodopsin. All
      non-rhodopsin GPCRs whose structures were determined so far were expressed in
      insect cells and the availability of other hosts was unknown. Recently, we
      succeeded to determine the structure of human histamine H(1) receptor (H(1)R)
      expressed in Pichia pastoris. Here, we report the expression and purification
      procedures of recombinant H(1)R used in the structural determination. The
      receptor was designed to possess a N-terminal 19-residue deletion and a
      replacement of the third cytoplasmic loop with T4-lysozyme. The receptor was
      verified to show similar binding activities with the receptor expressed in other
      hosts. The receptor was purified by the immobilized metal ion affinity
      chromatography and used for the crystallographic study that resulted in the
      successful structure determination.

PMID- 21903170
TI  - Growth hormone (GH) treatment acts on the endocrine and autocrine/paracrine
      GH/IGF-axis and on TNF-alpha expression in bony fish pituitary and immune organs.
AB  - There exist indications that the growth hormone (GH)/insulin-like growth factor
      (IGF) axis may play a role in fish immune regulation, and that interactions occur
      via tumour necrosis factor (TNF)-alpha at least in mammals, but no systematic
      data exist on potential changes in GH, IGF-I, IGF-II, GH receptor (GHR) and TNF
      alpha expression after GH treatment. Thus, we investigated in the Nile tilapia
      the influence of GH injections by real-time qPCR at different levels of the
      GH/IGF-axis (brain, pituitary, peripheral organs) with special emphasis on the
      immune organs head kidney and spleen. Endocrine IGF-I served as positive control
      for GH treatment efficiency. Basal TNF-alpha gene expression was detected in all
      organs investigated with the expression being most pronounced in brain. Two
      consecutive intraperitoneal injections of bream GH elevated liver IGF-I mRNA and
      plasma IGF-I concentration. Also liver IGF-II mRNA and TNF-alpha were increased
      while the GHR was downregulated. In brain, no change occurred in the expression
      levels of all genes investigated. GH gene expression was exclusively detected in
      the pituitary where the GH injections elevated both GH and IGF-I gene expression.
      In the head kidney, GH upregulated IGF-I mRNA to an even higher extent than liver
      IGF-I while IGF-II and GHR gene expressions were not affected. Also in the
      spleen, no change occurred in GHR mRNA, however, IGF-I and IGF-II mRNAs were
      increased. In correlation, in situ hybridisation showed a markedly higher amount
      of IGF-I mRNA in head kidney and spleen after GH injection. In both immune
      tissues, TNF-alpha gene expression showed a trend to decrease after GH treatment.
      The stimulation of IGF-I and also partially of IGF-II expression in the fish
      immune organs by GH indicates a local role of the IGFs in immune organ regulation
      while the differential changes in TNF-alpha support the in mammals postulated
      interactions with the GH/IGF-axis which demand for further investigations.

PMID- 21903168
TI  - A novel chimeric MOMP antigen expressed in Escherichia coli, Arabidopsis
      thaliana, and Daucus carota as a potential Chlamydia trachomatis vaccine
      candidate.
AB  - The major outer membrane protein (MOMP) of Chlamydia trachomatis is a highly
      antigenic and hydrophobic transmembrane protein. Our attempts to express the full
      length protein in a soluble form in Escherichia coli and in transgenic plants
      failed. A chimeric gene construct of C. trachomatis serovar E MOMP was designed
      in order to increase solubility of the MOMP protein but with retained
      antigenicity. The designed construct was successfully expressed in E. coli, in
      Arabidopsis thaliana, and in Daucus carota. The chimeric MOMP expressed in and
      purified from E. coli was used as antigen for production of antibodies in
      rabbits. The anti-chimeric MOMP antibodies recognized the corresponding protein
      in both E. coli and in transgenic plants, as well as in inactivated C.
      trachomatis elementary bodies. Transgenic Arabidopsis and carrots were
      characterized for the number of MOMP chimeric genetic inserts and for protein
      expression. Stable integration of the transgene and the corresponding protein
      expression were demonstrated in Arabidopsis plants over at least six generations.
      Transgenic carrots showed a high level of expression of the chimeric MOMP - up to
      3% of TSP.

PMID- 21903171
TI  - Cloning, distribution and primary immune characteristics of amphioxus alpha-2
      macroglobulin.
AB  - Alpha-2 macroglobulin (alpha(2)M), a broad-spectrum protease inhibitor, exists
      widely in vertebrates and invertebrates, but little information is available to
      date regarding alpha(2)M in amphioxus, an animal bridging from invertebrates to
      vertebrates. Here we first show that the full alpha(2)M cDNA of Branchiostoma
      japonicum (Bjalpha(2)m) contained 5545 bp with an open reading frame of 4593 bp
      encoding signal sequence of 16 amino acid residues and a mature protein of 1514
      residues. The calculated molecular mass and pI of mature Bjalpha(2)M were 164.2
      kDa and 4.6 respectively. Bjalpha(2)m was mainly expressed in the hepatic caecum
      and hind-gut in a tissue-specific manner, contrasting to the primary expression
      of alpha(2)M in vertebrate liver. Following challenge with lipopolysaccharide
      (LPS), Bjalpha(2)m expression was significantly up-regulated (7-folds) at 8 h and
      then declined to the base line at 16 h. Taken together, it is suggested that
      Bjalpha(2)M is an immune-relevant molecule possibly involved in the acute phase
      response via the digestive organs.

PMID- 21903172
TI  - Phylogeny of the mega-diverse Gelechioidea (Lepidoptera): adaptations and
      determinants of success.
AB  - The Gelechioidea, with 18,000 described and many more unnamed species ranks among
      the most diverse lepidopteran superfamilies. Nevertheless, their taxonomy has
      remained largely unresolved, and phylogenetic affinities among gelechioid
      families and lower taxa have been insufficiently understood. We constructed, for
      the first time, a comprehensive molecular phylogeny for the Gelechioidea. We
      sampled seven genes, in total 5466 base pairs, of 109 gelechioid taxa
      representing 32 of 37 recognized subfamilies, and two outgroup taxa. We used
      maximum likelihood methods and Bayesian inference to construct phylogenetic
      trees. We found that the families Autostichidae, Lecithoceridae, Xyloryctidae,
      and Oecophoridae s. str., in this order, are the most basally arising clades.
      Elachistidae s. l. was found to be paraphyletic, with families such as
      Gelechiidae and Cosmopterigidae nested within it, and Parametriotinae associated
      with several families previously considered unrelated to them. Using the
      phylogenetic trees, we examined patterns of life history evolution and
      determinants of the success of different lineages. Gelechioids express unusually
      wide variability in life-history strategies, including herbivorous, saprophagous,
      fungivorous, and carnivorous lineages. Most species are highly specialized in
      diet and other life history traits. The results suggest that either saprophagy
      was the ancestral feeding strategy from which herbivory evolved independently on
      multiple occasions, or that the ancestor was herbivorous with repeated origins of
      saprophagy. External feeding is an ancestral trait from which internal feeding
      evolved independently several times. In terms of species number, saprophages are
      dominant in Australia, while elsewhere several phytophagous lineages have
      extensively specialized and diversified. Internal feeding has remained a somewhat
      less generally adopted feeding mode, although in a few lineages significant
      radiations of leaf mining species have occurred. We conclude that diverse feeding
      modes, specialization among saprophages, repeated shifts to phytophagy, and a
      generally high specialization rate on single plant species (monophagy) are the
      major factors behind the success of the Gelechioidea.

PMID- 21903173
TI  - Bridging the gap between chemistry, physiology, and evolution: quantifying the
      functionality of sperm whale myoglobin mutants.
AB  - This work merges a large set of previously reported thermochemical data for
      myoglobin (Mb) mutants with a physiological model of O(2)-transport and -storage.
      The model allows a quantification of the functional proficiency of myoglobin (Mb)
      mutants under various physiological conditions, i.e. O(2)-consumption rate
      resembling workload, O(2) partial pressure resembling hypoxic stress, muscle cell
      size, and Mb concentration, resembling different organism-specific and
      compensatory variables. We find that O(2)-storage and -transport are distinct
      functions that rank mutants and wild type differently depending on O(2) partial
      pressure. Specifically, the wild type is near-optimal for storage at all
      conditions, but for transport only at severely hypoxic conditions. At normoxic
      conditions, low-affinity mutants are in fact better O(2)-transporters because
      they still have empty sites for O(2), giving rise to a larger [MbO(2)] gradient
      (more varying saturation curve). The distributions of functionality reveal that
      many mutants are near-neutral with respect to function, whereas only a few are
      strongly affected, and the variation in functionality increases dramatically at
      lower O(2) pressure. These results together show that conserved residues in wild
      type (WT) Mb were fixated under a selection pressure of low P(O2).

PMID- 21903174
TI  - Effects of dietary amino acids and repeated handling on stress response and brain
      monoaminergic neurotransmitters in Senegalese sole (Solea senegalensis)
      juveniles.
AB  - The present study aimed to assess the effects of increased availability of
      dietary amino acids (AA) on brain monoamine neurotransmitters and the metabolic
      processes resulting from stressful situations in fish. Senegalese sole (Solea
      senegalensis) juveniles (24.2+/-0.4g wet mass) were weekly subjected to an acute
      handling stressor (HDLG) or remained undisturbed (CTL). Additionally, both
      treatments were fed a control or a high protein (HP) diet (CTL, CTL HP, HDLG and
      HDLG HP). The HP diet slightly increased the levels of digestible indispensable
      AA, together with tyrosine and cysteine. Repeated handling induced a stress
      response after 14 and 28 days in fish held at both HDLG and HDLG HP treatments.
      While dietary treatment and handling stress activated the serotonergic system at
      14 days, these effects were not observed after 28 days. In addition, the HP diet
      minimized the decrease in plasma indispensable AA due to repeated handling stress
      after 28 days. It was concluded that HP diet decreased post-stress plasma glucose
      and lactate levels in HDLG HP specimens only at 14 days of treatment. Moreover,
      dietary treatment was also effective in stimulating DA synthesis and release,
      thus dietary phenylalanine supplementation can increase DA biosynthesis in fish.

PMID- 21903175
TI  - Metabolic networks evolve towards states of maximum entropy production.
AB  - A metabolic network can be described by a set of elementary modes or pathways
      representing discrete metabolic states that support cell function. We have
      recently shown that in the most likely metabolic state the usage probability of
      individual elementary modes is distributed according to the Boltzmann
      distribution law while complying with the principle of maximum entropy
      production. To demonstrate that a metabolic network evolves towards such state we
      have carried out adaptive evolution experiments with Thermoanaerobacterium
      saccharolyticum operating with a reduced metabolic functionality based on a
      reduced set of elementary modes. In such reduced metabolic network metabolic
      fluxes can be conveniently computed from the measured metabolite secretion
      pattern. Over a time span of 300 generations the specific growth rate of the
      strain continuously increased together with a continuous increase in the rate of
      entropy production. We show that the rate of entropy production asymptotically
      approaches the maximum entropy production rate predicted from the state when the
      usage probability of individual elementary modes is distributed according to the
      Boltzmann distribution. Therefore, the outcome of evolution of a complex
      biological system can be predicted in highly quantitative terms using basic
      statistical mechanical principles.

PMID- 21903176
TI  - Pharmacogenetics and cost-effectiveness analysis: a two-way street.
AB  - Genetic and proteomic information can be used to identify those patient groups
      who are most susceptible to a disease and those who are most likely to respond to
      particular pharmacological treatments. In this review we discuss the impact of
      cost-effectiveness analysis (CEA) regarding the way pharmacogenetics are adopted
      by healthcare systems and also, the potential impact of pharmacogenetics on the
      way CEA is conducted. We conclude that, although CEA can help incentivise the
      development of appropriate pharmacogenetic tests, when used inappropriately by
      payers or when ignored by developers, it can act as an obstacle to the adoption
      of health and efficiency improving technologies.

PMID- 21903177
TI  - Biotransformation enzyme-dependent formation of micronucleus and multinuclei in
      cell line V79-hCYP2E1-hSULT1A1 by 2-nitropropane and N-nitrosodimethylamine.
AB  - V79-hCYP2E1-hSULT1A1, a V79-derived cell line co-expressing both human CYP2E1 and
      SULT1A1, has been constructed and efficiently used in detection of the mutagenic
      activities of a number of promutagens. 2-Nitropropane (2-NP) and N
      nitrosodimethylamine (NDMA), both being hepatocarcinogenic to animals but
      inactive in standard genotoxicity assays in vitro, are activated to mutagenic
      metabolites by human SULT1A1 and CYP2E1, respectively. Nevertheless, little is
      known about the chromosomal effects of these two carcinogens. In the present
      study, we investigated the effects of 2-NP and NDMA on frequencies of
      micronucleated (F(mi)) and multinucleated cells (F(mu)) in V79-hCYP2E1-hSULT1A1
      cells. The results showed induction of both F(mi) and F(mu) by 2-NP and NDMA
      individually, and this effect was completely suppressed by relatively specific
      inhibitor of SULT1A1 and CYP2E1, i.e., pentachlorophenol and 1
      aminobenzotriazole, respectively. The F(mu)/F(mi) ratio in 2-NP groups was
      significantly higher than NDMA groups, probably indicating an aneugenic activity
      of 2-NP based on proposed F(mu)/F(mi) ratio as a simple index to discriminate
      aneugens from clastogens. The present study has established biotransformation
      enzyme-dependent formation of multinuclei and micronuclei induced by 2-NP and
      NDMA.

PMID- 21903178
TI  - Mutation rate of bacteriophage PhiX174 modified through changes in GATC sequence
      context.
AB  - Bacteriophage PhiX174 has a relatively high mutation rate of 10-6 substitutions
      per nucleotide per strand copying. A thirty-fold reduction in the mutation rate
      was achieved by introducing seven GATC sequences in its genome. This motif allows
      for methyl-directed mismatch repair and is strongly avoided in nature by PhiX174
      and other phages.

PMID- 21903179
TI  - Web tools for molecular epidemiology of tuberculosis.
AB  - In this study we explore publicly available web tools designed to use molecular
      epidemiological data to extract information that can be employed for the
      effective tracking and control of tuberculosis (TB). The application of molecular
      methods for the epidemiology of TB complement traditional approaches used in
      public health. DNA fingerprinting methods are now routinely employed in TB
      surveillance programs and are primarily used to detect recent transmissions and
      in outbreak investigations. Here we present web tools that facilitate systematic
      analysis of Mycobacterium tuberculosis complex (MTBC) genotype information and
      provide a view of the genetic diversity in the MTBC population. These tools help
      answer questions about the characteristics of MTBC strains, such as their
      pathogenicity, virulence, immunogenicity, transmissibility, drug-resistance
      profiles and host-pathogen associativity. They provide an integrated platform for
      researchers to use molecular epidemiological data to address current challenges
      in the understanding of TB dynamics and the characteristics of MTBC.

PMID- 21903180
TI  - Peptides from aminoacyl-tRNA synthetases can cure the defects due to mutations in
      mt tRNA genes.
AB  - Recent results from several laboratories have confirmed that human and yeast
      leucyl- and valyl-tRNA synthetases can rescue the respiratory defects due to
      mutations in mitochondrial tRNA genes. In this report we show that this effect
      cannot be ascribed to the catalytic activity per se and that isolated domains of
      aminoacyl-tRNA synthetases and even short peptides thereof have suppressing
      effects.

PMID- 21903181
TI  - Multiple pathways were involved in tubeimoside-1-induced cytotoxicity of HeLa
      cells.
AB  - The Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae) is a Chinese herb
      with anticancer potential. Its main active component tubeimoside-1 (TBMS1), a
      triterpenoid saponin, was previously proved as a potent anticancer
      chemotherapeutic agent; however, the molecular basis for its activities is still
      elusive. In the present study, subcellular proteomic study in the cytoplasm and
      membrane protein fractions extracted from HeLa cells revealed that proteins act
      as mediators of ROS generation and Ca(2+) regulation were substantially altered
      in expression upon TBMS1 stimuli. We also found that TBMS1 induced cell cycle
      arrest at G2/M phase accompanied by a decrease in G0/G1 phase in HeLa cells.
      Further biochemical studies showed that TBMS1 inhibited the levels of cyclinB1,
      Cdc2 and Cdc25C, but enhanced Chk2 phosphorylation. In addition, the cytoplasm
      sequestration of Cdc25C, Cip1/p21 induction and tubulin dyspolymerization also
      contributed to the TBMS1-mediated cell cycle arrest on the G2/M phase.

PMID- 21903182
TI  - Mass spectrometrical analysis of cuticular proteins from the wing of Hebemoia
      glaucippe (Linnaeus, 1758) (Lepidoptera: Pieridae).
AB  - Although several insect cuticular genes and proteins are annotated and an
      arthropod cuticular database is available, mass spectrometrical data on cuticular
      proteins and their post-translational modifications are limited. Wings from
      Hebemoia glaucippe were analyzed by scanning electron microscopy or homogenized,
      proteins were extracted and run on 2DE. In-gel digestion was carried out by using
      trypsin, chymotrypsin and Asp-N and subsequently the resulting peptides and post
      translational modifications were identified by ion trap tandem mass spectrometry
      (nano-LC-ESI-MS/MS; HCT). A complex wing skeleton and the cuticle of H. glaucippe
      were demonstrated. Cuticle protein 18.6, isoform A, pupal cuticle protein,
      cuticular protein CPR59A and two putative proteins, putative cuticular protein
      B2DBJ and putative cuticle protein CPG31 with two expression forms were
      identified. Two phosphorylation sites on the same peptide, T213 and S214, were
      identified on putative cuticle protein CPG31, quinone formation was observed at
      Y76 on cuticular protein CPR59A probably indicating the presence of post
      translational modifications. The results may be relevant for the interpretation
      of mechanoelastic and physical properties of these proteins. Along with the
      extraordinary architecture the proteinaceous matrix is probably representing or
      allowing the unusual aerodynamic function of the butterfly wing. Moreover, the
      results may be important for mechanisms of insecticide and drought resistance.

PMID- 21903183
TI  - [Jugular vein thrombosis in a patient addicted to intravenous drugs].

PMID- 21903184
TI  - Posterior cordectomy. Our experience.
AB  - OBJECTIVE: Several surgical procedures have been proposed for the treatment of
      respiratory distress secondary to bilateral cord palsy. We performed a
      retrospective study of our experience in posterior cordectomy with a laser CO(2),
      analysing the improvement of dyspnoea and voice quality after surgery. METHODS:
      This was a retrospective study of 13 cases (9 female, 4 male). The age range was
      25-79 years. Iatrogenic post-thyroidectomy (4 cases) was the most common
      aetiology of bilateral laryngeal palsy in our study. We assessed the subjective
      improvement of respiratory function and voice quality after laser surgery using
      the Spanish adaptation of the Voice Handicap Index (VHI). RESULTS: Dyspnoea
      improved in all patients. Two cases had a worsening of dyspnoea in the immediate
      postoperative period and one case was successfully solved with a new surgical
      intervention. After surgery, most of patients suffered from mild or middle
      dysphonia. CONCLUSIONS: The posterior cordectomy is an easy, safe and effective
      treatment for dyspnoea secondary to bilateral laryngeal palsy, maintaining
      acceptable voice quality.

PMID- 21903185
TI  - Late diagnosis of isolated agenesis of cranial nerve VIII.

PMID- 21903186
TI  - The whole is indeed more than the sum of its parts: perceptual averaging in the
      absence of individual item representation.
AB  - We tested Ariely's (2001) proposal that the visual system represents the overall
      statistical properties of sets of objects against alternative accounts of rapid
      averaging involving sub-sampling strategies. In four experiments, observers could
      rapidly extract the mean size of a set of circles presented in an RSVP sequence,
      but could not reliably identify individual members. Experiment 1 contrasted
      performance on a member identification task with performance on a mean judgment
      task, and showed that the tasks could be dissociated based on whether the test
      probe was presented before or after the sequence, suggesting that member
      identification and mean judgment are subserved by different mechanisms. In
      Experiment 2, we confirmed that when given a choice between a probe corresponding
      to the mean size of the set and a foil corresponding to the mean of the smallest
      and largest items only, the former is preferred to the latter, even when
      observers are explicitly instructed to average only the smallest and largest
      items. Experiment 3 showed that a test item corresponding to the mean size of the
      set could be reliably discriminated from a foil but the largest item in the set,
      differing by an equivalent amount, could not. In Experiment 4, observers rejected
      test items dissimilar to the mean size of the set in a member identification
      task, favoring test items that corresponded to the mean of the set over items
      that were actually shown. These findings suggest that mean representation is
      accomplished without explicitly encoding individual items.

PMID- 21903187
TI  - [Products for hand hygiene and antisepsis: use by health professionals and
      relationship with hand eczema].
AB  - Hand hygiene is the most important measure for the prevention of nosocomial
      infection. We describe the different products available for hygiene and
      antisepsis of the hands and the use of these products in daily practice. Hand
      hygiene products such as soaps and detergents are a cause of irritant dermatitis
      in health professionals. This irritation is one of the principal factors
      affecting their use in clinical practice. Alcohol-based products are better
      tolerated and less irritant than soap and water; irritation should not therefore
      be a limiting factor in the use of these products and they are to be recommended
      in place of soap and water. Informative and continued education programs could
      increase their use.

PMID- 21903188
TI  - A different perspective on income inequality in America.

PMID- 21903189
TI  - Reflections on a medical school symphony orchestra.

PMID- 21903190
TI  - Prior knowledge of HPV status improves detection of CIN2+ by cytology screening.
AB  - OBJECTIVE: The objective of the study was to investigate whether knowledge of
      human papillomavirus (HPV) deoxyribonucleic acid test results increases
      sensitivity of guided cytology screening for the detection of cervical
      intraepithelial neoplasia (CIN)-2 or higher-grade cervical lesions. STUDY DESIGN:
      This was a prospective colposcopy-controlled study of 2905 BD SurePath samples to
      identify cases with CIN2+ within a 24 month follow-up period. Sensitivity and
      specificity to detect CIN2+ was evaluated, comparing guided cytology screening
      with and without prior knowledge of HPV status. RESULTS: Prior knowledge of HPV
      status resulted in significantly higher detection rate of CIN2+ compared with
      screening blinded to HPV status (P = .005) with limited loss of specificity (P =
      .026). Gain in sensitivity is higher in older women (43.8%, P = .008) vs in
      younger women (10.2%, P = .317), whereas loss of specificity is more pronounced
      in younger women (P < .001) vs older women (P = .729). CONCLUSION: Guided
      cytological screening performed with prior knowledge of HPV status results in an
      improved detection of CIN2 or higher-grade lesions.

PMID- 21903191
TI  - Angiogenic factors as diagnostic tests for preeclampsia: a performance comparison
      between two commercial immunoassays.
AB  - OBJECTIVE: Placental growth factor and soluble Fms-like tyrosine kinase-1 may be
      potential diagnostic markers of preeclampsia. We compared performances of 2
      immunoassays, the Triage placental growth factor assay and the Elecsys soluble
      Fms-like tyrosine kinase-1/placental growth factor ratio in diagnosing
      preeclampsia. STUDY DESIGN: A single site, case-control study of 44 patients with
      preeclampsia and 84 matched normal pregnant controls. Samples were collected at
      the time of diagnosis. Assays were performed according to product inserts.
      RESULTS: Both assays had optimal performance in diagnosing early-onset
      preeclampsia with area under the receiver operating characteristic curves of 0.99
      (Triage: 100% sensitivity, 96% specificity; Elecsys: 64% sensitivity, 100%
      specificity for early-onset preeclampsia). Reassignment of the Elecsys cutoff for
      a positive test based on receiver operating characteristic curves increased
      sensitivity to 92%. CONCLUSION: Using product insert cutoffs, Triage appears to
      have greater sensitivity at only a small reduction in specificity compared with
      Elecsys in the diagnosis of early-onset preeclampsia. A different cutoff may
      improve Elecsys sensitivity.

PMID- 21903192
TI  - Potential reduction in neural tube defects associated with use of Metafolin
      fortified oral contraceptives in the United States.
AB  - OBJECTIVE: The objective of the study was to estimate the potential reduction of
      neural tube defects (NTDs) through the use of Metafolin-fortified oral
      contraceptives (OCs) in the United States. STUDY DESIGN: A population-based
      decision analytic model was developed to estimate the benefits of increased red
      blood cell (RBC) folate levels through the use of Metafolin-fortified OCs on NTD
      risk during pregnancy. We modeled women who began the year taking Metafolin
      fortified or traditional OCs. Folate levels were derived from the National Health
      and Nutrition Examination Survey and clinical trial data. NTD risk was estimated
      by applying a published risk equation to respective RBC folate levels. RESULTS:
      The number of predicted NTD cases declined by 23.7% to 31.4%, depending on median
      baseline folate levels in women taking a fortified OC compared with taking a
      traditional OC. CONCLUSION: Metafolin-fortified OCs have the potential to reduce
      the number of folate-dependent NTDs among current and recent OC users.

PMID- 21903193
TI  - Factors influencing uptake of intrauterine devices among postpartum adolescents:
      a qualitative study.
AB  - OBJECTIVE: We assessed barriers and facilitators to uptake of the intrauterine
      device (IUD) among primiparous African American adolescent mothers. STUDY DESIGN:
      Twenty participants who expressed IUD desire completed 4-5 qualitative interviews
      during the first postpartum year as part of a larger longitudinal study.
      Transcripts were analyzed for salient themes using a grounded theory approach to
      content analysis. RESULTS: Twelve participants did not obtain IUDs and instead
      used condoms, used no method, or intermittently used hormonal methods, resulting
      in 3 repeat pregnancies. Outdated IUD eligibility requirements, long wait times,
      lack of insurance coverage, and fear of IUD-related side effects precluded or
      delayed uptake. Facilitators to IUD uptake included strong recommendations from
      providers or family members, planning for IUD during pregnancy, and perceived
      reproductive autonomy. CONCLUSION: Postpartum adolescents may reduce their risk
      of rapid repeat pregnancy by using IUDs. Providers and members of adolescents'
      support networks can be instrumental in method adoption.

PMID- 21903194
TI  - Antenatal suspicion of ischemic placental disease and coexistence of maternal and
      fetal placental disease: analysis of over 500 cases.
AB  - OBJECTIVE: To investigate the antenatal suspicion of placental disease and the
      coexistence of maternal and fetal placental ischemic disease. STUDY DESIGN: A
      prospective cohort study on normally formed singleton infants from 2000 to 2008
      inclusive with placental ischemic disease. RESULTS: Uteroplacental ischemia or
      fetoplacental thrombotic vasculopathy was identified in 511 of 74,857 births
      (7/1000 births). Four hundred fifty-nine cases met the inclusion criteria.
      Maternal and fetal placental vascular disease coexisted in 9.2% (n = 42) of
      cases. Placental ischemic disease was suspected antenatally in 70% (324/459).
      Maternal placental disease occurred in 40% (184/459) and 30% (140/459) had fetal
      pathology. The perinatal mortality rate was 12.7/1000. Antenatal suspicion of
      placental disease led to increased obstetric intervention and delivery of small
      for-gestational age infants. CONCLUSION: Maternal and fetoplacental vascular
      disease coexisted in 9.2%. Placental disease was suspected antenatally in 70% of
      cases and was associated with increased rates of obstetric intervention.

PMID- 21903195
TI  - [Assessment of left ventricular twist mechanics by two-dimensional strain in
      severe aortic stenosis with preserved ejection fraction].
AB  - Left ventricular (LV) twist is increased in aortic stenosis (AS) and the
      hypothesis of a compensatory mechanism is suggested but not established. Our aim
      was to assess LV twist mechanics in severe AS (<1cm(2) or 0.6cm(2)/m(2)) with
      preserved LV ejection fraction (LVEF>50%), and to analyze its relationship with
      LV systolic longitudinal function, early impaired in this setting, LV diastolic
      function, and symptomatic status. METHODS: Forty-five consecutive patients with
      severe AS and preserved LVEF (mean age 73+/-11 years, 47% female, LVEF 68+/-11%,
      67% symptomatic) underwent a transthoracic echocardiography including a
      bidimensional strain analysis by speckle tracking method, and were compared to a
      control group matched for age and sex (n=15). Global longitudinal strain (GLS)
      was measured using the four, two, and three apical views, and LV twist mechanics
      from the basal and apical short axis views. LV twist was defined as the net
      difference between apical and basal rotation, and LV twisting and untwisting rate
      (in degrees /s) were derived from twist curves. RESULTS: Peak apical rotation, LV
      twist (25+/-8 degrees  vs 20+/-6), as well as peak systolic and diastolic apical
      rotation rate, and peak LV twisting rate were significantly higher in patients
      with AS when compared to controls (all, P<0.05), whereas, the other parameters of
      LV twist mechanics including basal rotation, were not significantly different
      between groups. By contrast, the GLS was significantly lower in patients with AS
      when compared to controls (-17.9+/-4 vs -20.5+/-2%, P<0.01). In addition, the GLS
      was significantly correlated to LV torsion (r=-0.42, P<0.01). Moreover, LV twist
      progressively impaired with the worsening of diastolic dysfunction and with
      symptoms onset. CONCLUSION: LV twist is increased in severe AS with preserved
      LVEF, compensating the impairment of systolic longitudinal function. However,
      above a certain threshold LV twist deteriorates, attesting the failure of the
      compensatory mechanisms, leading to advanced diastolic dysfunction and symptom
      onset.

PMID- 21903196
TI  - Plaque rupture and morphological characteristics of the culprit lesion in acute
      coronary syndromes without significant angiographic lesion: analysis by
      intravascular ultrasound.
AB  - PURPOSE: To evaluate by intravascular ultrasound (IVUS) the characteristics of
      the culprit lesion with plaque rupture without significant angiographic stenosis
      after acute coronary syndromes (ACS). PATIENTS AND METHODS: After ACS, IVUS was
      performed in 68 patients (46.8 years+/-11.9) without significant angiographic
      stenosis (31+/-15%). Plaque rupture was defined as a cavity within the plaque,
      communicating with the arterial lumen and having an overlying residual fibrous
      cap fragment. Qualitative analysis defined the type of plaque, and quantitative
      analysis evaluated plaque plus media area, plaque volume, plaque burden, and
      arterial remodeling index. Patients were divided into two groups: Group I with
      plaque rupture (25 patients) and Group II without plaque rupture (43 patients).
      RESULTS: All patients with rupture showed soft or mixed plaque but no calcified
      plaque. In Group I, plaque rupture was associated with a larger plaque burden
      (49.8+/-12.3% vs. 39.8+/-12.1%, P<.0005), a more significant plaque plus media
      area (7.44+/-2.9 vs. 5.24+/-2.4mm(2), P<.001), a greater plaque volume (151.9+/
      103.4 vs. 99.2+/-81.6mm(3), P<.007), and a higher ratio of plaque volume over
      length (8.0+/-3.8 vs. 5.6+/-3.7mm(3)/mm, P<.003). In Group I, positive remodeling
      was more frequent than intermediate remodeling (P<.03) or negative remodeling
      (P<.005). In Group II, there was no significant difference between the three
      types of remodeling. CONCLUSION: The plaque ruptures responsible for ACS
      frequently appear on voluminous plaques with a large plaque burden and positive
      arterial remodeling.

PMID- 21903197
TI  - An in vitro comparison of dentifrice formulations in three distinct oral
      microbiotas.
AB  - OBJECTIVES: In vitro biofilm models, representative of some aspects of nascent,
      supra-gingival plaques (Hydroxyapatite Disc Biofilm Models), developed supra
      gingival plaques (Modified Drip-flow Biofilm Reactors) and sub-gingival plaques
      (Multiple Sorbarod Devices) were used to compare the antimicrobial effects of a
      triclosan-containing dentifrice with a stannous fluoride and zinc lactate
      combination. DESIGN: Triplicate salivary biofilm microcosms were maintained for
      2d (hydroxyapatite discs), 5d (Sorbarods) or up to 6d (drip flow reactors).
      Dentifrice slurries (10%, w/v) were added once to the discs and repeatedly to the
      Drip Flow Reactors and Sorbarods. Plaques were analysed by differential culture
      and gravimetrically. RESULTS: Whilst both dentifrices were comparably effective
      at reducing viability and plaque accumulation in mature supragingival plaques,
      the triclosan dentifrice produced comparatively larger reductions in total
      streptococci and anaerobes in nascent plaques (p<0.05) and greater reductions in
      Gram-negative anaerobes and streptococci in subgingival plaques. CONCLUSIONS: We
      have used a multi-model approach to determine the effectiveness and specificity
      of dentifrices against compositionally distinct plaques. Whilst both formations
      reduced bacterial viability and plaque accumulation, their effects could be
      differentiated in nascent and deep plaques where the triclosan dentifrice caused
      larger viability reductions.

PMID- 21903198
TI  - Reduced proactive inhibition in schizophrenia is related to corticostriatal
      dysfunction and poor working memory.
AB  - BACKGROUND: Inhibitory control is central to executive functioning and appears
      deficient in schizophrenia. However, it is unclear how inhibitory control is
      affected, what the underlying neural mechanisms are, whether these deficits are
      related to the illness itself or to increased risk for the illness, and whether
      there is a relation to impairments in other executive functions. METHODS: We used
      functional magnetic resonance imaging to investigate two forms of inhibitory
      control: proactive inhibition (anticipation of stopping) and reactive inhibition
      (outright stopping). Twenty-four schizophrenia patients, 24 unaffected siblings,
      and 24 healthy control subjects performed a modified version of the stop-signal
      paradigm. To assess the relation between performance on inhibitory control and
      other executive functions, we correlated inhibitory control indices with working
      memory span. RESULTS: Compared with control subjects, proactive inhibition was
      reduced in patients and siblings. Reactive inhibition was unaffected. Reduced
      proactive inhibition was associated with a failure to activate the right
      striatum, the right inferior frontal cortex, and the left and right
      temporoparietal junction. Activation during reactive inhibition was unaffected.
      Those patients with the least proactive inhibition also showed the shortest
      working memory span. CONCLUSIONS: These results suggest that schizophrenia is
      associated with reduced proactive inhibition, probably resulting from
      corticostriatal dysfunction. This deficit is related to an increased risk for
      schizophrenia and likely reflects a general executive function deficit rather
      than a specific inhibitory control impairment.

PMID- 21903200
TI  - Changes in gray matter volume and white matter microstructure in adolescents with
      obsessive-compulsive disorder.
AB  - BACKGROUND: There is a paucity of neuroimaging data in pediatric-onset obsessive
      compulsive disorder (OCD). This multimodal neuroimaging study aimed to identify
      structural gray (GM) and white matter (WM) microstructure changes in pediatric
      OCD. METHODS: We obtained structural and diffusion tensor magnetic resonance
      images from 26 OCD patients and 26 matched healthy adolescents. We carried out a
      series of image analyses including, volumetric and shape analysis of subcortical
      gray structures, as well as voxel-based morphometry on GM volume and fractional
      anisotropy of the WM. RESULTS: Patients had increased GM volume in the caudate
      bilaterally and right putamen. Shape analyses revealed specific hypertrophy of
      the dorsal caudate in pediatric OCD. The striatum was larger in healthy boys
      compared with healthy girls, whereas such a gender effect was not seen in the OCD
      group. OCD subjects showed higher fractional anisotropy values in left inferior
      longitudinal fasciculus, bilateral superior longitudinal fasciculus, right
      inferior fronto-occipital fasciculus, bilateral corticospinal tract, corpus
      callosum splenium and genu, bilateral forceps major, bilateral forceps minor,
      left cingulum, and right uncinate fasciculus. OCD symptom severity was positively
      correlated with GM volume in right insula, posterior orbitofrontal cortex,
      brainstem, and cerebellum and inversely correlated with widespread reduction in
      cortical GM volume. Furthermore, symptom severity positively correlated with
      increased WM fractional anisotropy in various WM tracts, including the anterior
      limb of the internal capsule. CONCLUSIONS: Adolescents with OCD had a wide range
      of GM and WM changes compared to healthy control subjects that are broadly
      consistent with those identified in the adult OCD literature but are more
      extensive.

PMID- 21903199
TI  - Association of somatic and cognitive depressive symptoms and biomarkers in acute
      myocardial infarction: insights from the translational research investigating
      underlying disparities in acute myocardial infarction patients' health status
      registry.
AB  - BACKGROUND: Somatic depressive symptoms and certain biomarkers are each
      associated with worse acute myocardial infarction (AMI) prognosis, but the
      relationship between depressive symptom domains and inflammatory, neurohormonal,
      and coagulation markers is unknown. METHODS: We examined the relationship between
      depressive symptoms and 1-month biomarker levels (high-sensitivity C-reactive
      protein [hs-CRP], N-terminal pro-brain natriuretic peptide [NT-proBNP], white
      blood cell [WBC], platelet counts) in 1265 AMI patients. Depressive symptoms (9
      item Patient Health Questionnaire) were assessed during index hospitalization and
      categorized as somatic or cognitive. Using median regression models, the upper
      quartile of somatic and cognitive depression scores and each biomarker were
      compared with the lower three quartiles, adjusting for site, demographics, and
      clinical characteristics. RESULTS: Although hs-CRP values were higher in patients
      with somatic symptoms, this association was attenuated after adjustment (B(per SD
      increase) = .02, 95% confidence interval: .00; .05, p = .07). WBC count was
      independently associated with somatic depressive symptoms (B(per SD increase) =
      .28, 95% confidence interval: .12; .44, p < .001). Cognitive depressive symptoms
      were not associated with hs-CRP or WBC count. Neither dimension was associated
      with NT-proBNP or platelet levels. For each biomarker, the depression dimensions
      explained <1% of their variation. CONCLUSIONS: Neither somatic nor cognitive
      depressive symptoms were meaningfully associated with hs-CRP, NT-proBNP, WBC, or
      platelet counts 1 month after AMI, suggesting that the association between
      depression and long-term outcomes may be unrelated to these biomarkers. Future
      research should explore other biomarkers to better illuminate pathways by which
      depression adversely impacts AMI prognosis.

PMID- 21903201
TI  - Lipopolysaccharide structures of Helicobacter pylori wild-type strain 26695 and
      26695 HP0826::Kan mutant devoid of the O-chain polysaccharide component.
AB  - We describe a re-investigation of the structure of the lipopolysaccharide (LPS)
      from Helicobacter pylori genomic strain 26695 and its corresponding HP0826::Kan
      mutant lacking the O-chain component based on the in-depth NMR analysis of the
      oligosaccharide products obtained through the use of various degradation
      procedures performed on the purified LPS from both strains, as well as CE-MS
      data. New structural evidence indicates the presence of the linear arrangement of
      glucan and heptan portions of the LPS attached through -6-alpha-DDHep-3-alpha-L
      Fuc-3-beta-GlcNAc- fragment to the inner core DD-heptose residue. This structure
      differs from previously reported structures of the H. pylori 26695 LPS in several
      aspects.

PMID- 21903202
TI  - Differentiating the 2,3-diols of glucopyranosides by 4,6-O-benzylidene-protected
      1,2-D-glucopyranosylorthoesters strategy.
AB  - A facile and efficient method to differentiate the 2,3-diols of glucopyranosides
      based on 1,2-orthoesters strategy was developed. Stable thioglucosides were
      employed as the starting materials to prepare the corresponding 1,2-orthoesters.
      When treated with HCl aqueous solution and followed with Et(3)N, differentiation
      of the 2,3-diols was efficiently achieved along with the generation of a
      convertible anomeric hydroxyl group. In addition, an easy and practical method
      based on NOE was proposed to determine whether the 1,2-orthoesters were endo-type
      or exo-type.

PMID- 21903203
TI  - Wide sugar substrate specificity of galactokinase from Streptococcus pneumoniae
      TIGR4.
AB  - Galactokinases (GALK) have attracted significant research attention for their
      potential application in the enzymatic synthesis of unique sugar phosphates. The
      galactokinase (GalKSpe4) cloned from Streptococcus pneumoniae TIGR4 had a
      temperature optimum of 45 degrees C, and a pH optimum of 8.0. The substrate
      specificity and kinetics studies revealed that GalKSpe4 had moderate activity
      toward glucose, in contrast with very low or no activity observed in other
      previously reported GALKs. Most interestingly, GalKSpe4 exhibited activity for
      GalNAc, which had never been recorded in other GALKs found by now. This is the
      first time to report that bacterial GALK can recognize GalNAc.

PMID- 21903204
TI  - Regioselective monoacylation of 2-O-alpha-D-glucopyranosyl-L-ascorbic acid by a
      polymer catalyst in N,N-dimethylformamide.
AB  - 6-O-Dodecanoyl-2-O-alpha-D-glucopyranosyl-L-ascorbic acid (6-sDode-AA-2G) was
      synthesized from 2-O-alpha-D-glucopyranosyl-L-ascorbic acid and lauric anhydride
      with a polymer catalyst, poly(4-vinylpyridine), in N,N-dimethylformamide without
      the introduction of protecting groups. The optimum reaction conditions enabled 6
      sDode-AA-2G to be synthesized in a yield of 49.7%. The yield and the
      regioselectivity in this method were far superior to those in our previous method
      by using an enzyme. The polymer catalyst could be recycled more than five times
      without any significant activity loss.

PMID- 21903205
TI  - Studies on the synthesis and the antimicrobial and antioxidant activities of a
      novel class of fluorescein-based glycosides.
AB  - Facile glycosylation of a fluorescein diol derivative with per-O-acetyl/benzoyl
      sugar derivatives using BF(3).Et(2)O catalyst resulted in the formation of the
      expected glycosides in 54-66% yield. The biological screening of the glycosides
      against different microbes shows good inhibitory activity. The antioxidant
      activity of the fluorescein-based glycosides shows remarkable inhibition (IC(50)
      ~80%).

PMID- 21903206
TI  - Inflammation-inducing Th1 and Th17 cells differ in their expression patterns of
      apoptosis-related molecules.
AB  - Th1 cells are remarkably more susceptible to activation induced cell death than
      Th17. Here, we compared cultures of these two cell subpopulations for their
      expression of apoptosis-related molecules when re-exposed to their specific
      antigen. We also compared the expression of apoptosis-related molecules in the
      mouse eye with inflammation induced by Th1 or Th17 cells. Using qPCR we found
      that the mRNA transcript levels of the majority of tested apoptosis-related
      molecules were higher in the Th1 cultures, and in eyes with Th1-induced
      inflammation. Apoptotic intrinsic pathway molecules played minor roles in the
      processes in vitro or in vivo, whereas extrinsic pathway molecules, as well as PD
      1, its ligands and Tim3, were heavily involved.

PMID- 21903209
TI  - Romantic relationship status biases memory of faces of attractive opposite-sex
      others: evidence from a reverse-correlation paradigm.
AB  - Previous research has demonstrated that, presumably as a way to protect one's
      current romantic relationship, individuals involved in a heterosexual romantic
      relationship tend to give lower attractiveness ratings to attractive opposite-sex
      others as compared to uninvolved individuals (i.e., the derogation effect). The
      present study importantly extends this research by examining whether romantic
      relationship status actually biases memory for the facial appearance of
      attractive (vs. unattractive) mates. To address this issue, we used a reverse
      correlation technique (Mangini & Biederman, 2004), originally developed to get a
      visual approximation of an individual's internal representation of a target
      category or person. In line with the derogation effect, results demonstrated that
      romantically involved (vs. uninvolved) individuals indeed held a less attractive
      memory of a previously encountered attractive mate's face. Interestingly, they
      also held a more attractive memory of an unattractive mate's face as compared to
      uninvolved individuals. This latter finding may suggest that romantically
      involved (as compared to uninvolved) individuals differentiate opposite-sex
      others along the attractiveness dimension less.

PMID- 21903207
TI  - Enhancement of HLA class II-restricted CD4+ T cell recognition of human melanoma
      cells following treatment with bryostatin-1.
AB  - The majority of melanoma cells express detectable levels of HLA class II
      proteins, and an increased threshold of cell surface class II is crucial for the
      stimulation of CD4+ T cells. Bryostatin-1, a protein kinase C (PKC) activator,
      has been considered as a potent chemotherapeutic agent in a variety of in vitro
      tumor models. Little is known about the role of bryostatin-1 in HLA class II Ag
      presentation and immune activation in malignant tumors, especially in melanoma.
      In this study, we show that bryostatin-1 treatment enhances CD4+ T cell
      recognition of melanoma cells in the context of HLA class II molecules. We also
      show that bryostatin-1 treatment of melanoma cells increases class II protein
      levels by upregulating the class II transactivator (CIITA) gene. Flow cytometry
      and confocal microscopic analyses revealed that bryostatin-1 treatment
      upregulated the expression of costimulatory molecules (CD80 and CD86) in melanoma
      cells, which could prolong the interaction of immune cells and tumors. Bryostatin
      1 also induced cellular differentiation in melanoma cells, and reduced
      tumorigenic factors such as pro-cathepsins and matrix-metalloproteinase-9. These
      data suggest that bryostatin-1 could be used as a chemo-immunotherapeutic agent
      for reducing tumorigenic potential of melanoma cells while enhancing CD4+ T cell
      recognition to prevent tumor recurrence.

PMID- 21903211
TI  - [Treatment of anemia in heart failure: iron first?].

PMID- 21903210
TI  - Blood-based biomarkers of selenium and thyroid status indicate possible adverse
      biological effects of mercury and polychlorinated biphenyls in Southern Beaufort
      Sea polar bears.
AB  - We examined biomarkers of selenium status (whole blood Se; serum Se; glutathione
      peroxidase activity) and thyroid status (concentrations and ratios of thyroxine,
      T4; tri-iodothyronine, T3; albumin) in polar bears to assess variations among
      cohorts, and relationships to circulating concentrations of contaminants.
      Concentrations of total mercury (Hg) in whole blood were similar among cohorts
      (prime aged males and females, older animals, ages>=16 years, and young animals,
      ages 1-5 years; 48.44+/-35. 81; p=0.253). Concentrations of sum of seven
      polychlorinated biphenyls (?PCB7) in whole blood were greater in females (with
      and without cubs, 26.44+/-25.82 ng/g ww) and young (26.81+/-10.67 ng/g ww)
      compared to males (8.88+/-5.76 ng/g ww, p<0.001), and significantly related to
      reduced body condition scores (p<0.001). Concentrations of Se and albumin were
      significantly greater in males than females (whole blood Se, males, 42.34 pmol/g
      ww, females, 36.25+/-6.27 pmol/g ww, p=0.019; albumin, males, 4.34+/-0.34 g/dl,
      females, 4.10+/-0.29 g/dL, p=0.018). Glutathione peroxidase activity ranged from
      109.1 to 207.8 mU/mg hemoglobin, but did not differ significantly by sex or age
      (p>0.08). Thyroid hormones were greater in females (solitary females and females
      with cubs) compared to males (p<0.001). Biomarkers of Se status and
      concentrations of T3 were significantly positively related to Hg in all prime
      aged polar bears (p<0.03). Albumin concentrations were significantly positively
      related to total TT4, and significantly negatively related to concentrations of
      ?PCB7 (p<0.003). Total thyroxine (TT4) was significantly negatively associated
      with blood concentrations of ?PCB7 in solitary females (p=0.045). These data
      suggest that female polar bears were more susceptible to changes in blood-based
      biomarkers of selenium and thyroid status than males. Further classifications of
      the physiologic states of polar bears and repeated measures of individuals over
      time are needed to accurately assess the biological impact of combined toxicant
      exposures.

PMID- 21903212
TI  - Current status and perspectives of the development of dental research in
      biological anthropology of Argentina: introduction and conclusions of the
      symposium.
AB  - This paper describes and discusses the research in the field of dental
      anthropology in Argentina. It has been presented at the symposium entitled "The
      development of dental research in Argentine Biological Anthropology: current
      status and perspectives", coordinated by the authors at the IX National Meeting
      of Biological Anthropology of Argentina, Puerto Madryn, 20th-23rd October 2009.
      The aim of the symposium was to present new results and future prospects of this
      discipline in the country and to create a forum for discussion of current
      research within this field. Six contributions that focused on the study of teeth
      from different perspectives and analysed bioarchaeological samples from different
      areas of Argentina (Central Highlands, Pampa and Patagonia) were presented. After
      the presentations, a discussion about the state of the art of dental research in
      the country was generated, in which the need for the generation of methodological
      consensus on the criteria for the evaluation of the variables considered was
      stated, so that research conducted in different areas can be compared. In short,
      the contributions of this symposium provide insights into the diversity of dental
      anthropology in contemporary Argentina and the potential of these types of
      studies to gain important information about biological and cultural aspects of
      the native populations in the country.

PMID- 21903214
TI  - Determining the optimal system-specific cut-off frequencies for filtering in
      vitro upper extremity impact force and acceleration data by residual analysis.
AB  - The fundamental nature of impact testing requires a cautious approach to signal
      processing, to minimize noise while preserving important signal information.
      However, few recommendations exist regarding the most suitable filter frequency
      cut-offs to achieve these goals. Therefore, the purpose of this investigation is
      twofold: to illustrate how residual analysis can be utilized to quantify optimal
      system-specific filter cut-off frequencies for force, moment, and acceleration
      data resulting from in-vitro upper extremity impacts, and to show how optimal cut
      off frequencies can vary based on impact condition intensity. Eight human cadaver
      radii specimens were impacted with a pneumatic impact testing device at impact
      energies that increased from 20J, in 10J increments, until fracture occurred. The
      optimal filter cut-off frequency for pre-fracture and fracture trials was
      determined with a residual analysis performed on all force and acceleration
      waveforms. Force and acceleration data were filtered with a dual pass, 4th order
      Butterworth filter at each of 14 different cut-off values ranging from 60Hz to
      1500Hz. Mean (SD) pre-fracture and fracture optimal cut-off frequencies for the
      force variables were 605.8 (82.7)Hz and 513.9 (79.5)Hz, respectively. Differences
      in the optimal cut-off frequency were also found between signals (e.g. Fx (medial
      lateral), Fy (superior-inferior), Fz (anterior-posterior)) within the same test.
      These optimal cut-off frequencies do not universally agree with the
      recommendations of filtering all upper extremity impact data using a cut-off
      frequency of 600Hz. This highlights the importance of quantifying the filter
      frequency cut-offs specific to the instrumentation and experimental set-up.
      Improper digital filtering may lead to erroneous results and a lack of
      standardized approaches makes it difficult to compare findings of in-vitro
      dynamic testing between laboratories.

PMID- 21903213
TI  - Scaphoid morphology and clinical outcomes in scaphoid reconstructions.
AB  - Scaphoid malunion and carpal malalignment can result after scaphoid
      reconstruction, if the two fragments are not properly reduced before fixation.
      However, currently there is no information about which degree of deformity or
      malalignment can be tolerated without impairing clinical function. The purpose of
      this study was to investigate the influence of the scaphoid morphology and carpal
      alignment on clinical outcomes after scaphoid reconstruction. A total of 65
      patients with an average age of 29 years were followed-up after a mean period of
      45 months. In all patients, osseous union after a first-time scaphoid
      reconstruction in the middle third had been confirmed. Scapholunate (SL) and
      radiolunate (RL) angles were obtained on plain radiographs as were intrascaphoid
      (ISA) and dorsal cortical (DCA) angles and the height/length (H/L) ratio of the
      reconstructed scaphoid on computed tomography (CT) scans. These parameters were
      correlated with clinical outcome measures. RL angles correlated significantly
      with wrist range of motion, grip strength and pain levels, whilst SL angles, ISA,
      DCA and H/L ratio failed to show significant correlations. Our data suggest that
      clinical outcome is correlated with correct restoration of bone morphology and
      carpal alignment. After reconstruction, the RL angle should not exceed 10 degrees
      .

PMID- 21903215
TI  - Separation of phenolic acids from natural plant extracts using molecularly
      imprinted anion-exchange polymer confined ionic liquids.
AB  - Polymer-confined ionic liquids were used for the separation of phenolic acids
      from natural plant extract by utilizing an anion-exchange mechanism. They were
      synthesized using molecular imprinting technique to reduce non-directional ion
      ion interactions during anion-exchange and other interactions with interference
      substances that could decrease selectivity. A suitable sorbent for phenolic acid
      separation could be identified based on the adsorption behaviors of phenolic
      acids on different polymer-confined ionic liquids. Thus, the developed ionic
      liquid-based molecularly imprinted anion-exchange polymer (IMAP) achieved high
      recovery rates by solid-phase extraction of phenolic acids from Salicornia
      herbacea L. extract: 90.1% for protocatechuic acid, 95.5% for ferulic acid and
      96.6% for caffeic acid. Moreover, the phenolic acids were separable from each
      other by repeated solid phase extraction cycles. The proposed method could be
      used to separate other phenolic acids or organic acids from complex samples.

PMID- 21903216
TI  - Characterization of N-acetyltryptophan degradation products in concentrated human
      serum albumin solutions and development of an automated high performance liquid
      chromatography-mass spectrometry method for their quantitation.
AB  - N-acetyltryptophan (NAT) has long been used as a stabilizer in some protein
      solutions, such as human serum albumin, to prevent oxidative protein degradation.
      However, the fate of NAT has not been discussed in literature. Two NAT
      degradation products have been observed in concentrated albumin solutions (20%
      and 25%) and identified as 1-acetyl-3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3
      b]indole-2-carboxylic acid and 1-acetyl-3a,8a-dihydroxy-1,2,3,3a,8,8a
      hexahydropyrrolo[2,3-b]indole-2-carboxylic acid. To monitor the levels of these
      two previously unidentified NAT degradation products in concentrated albumin
      solutions, a fully automated method, incorporating online size exclusion
      chromatography (SEC) trapping and reversed-phase high performance liquid
      chromatography-mass spectrometry (HPLC-MS) with multiple reaction monitoring
      (MRM) analysis, has been developed and validated for their quantitative analysis.
      The method does not require an internal standard. The only sample manipulation is
      to obtain an albumin concentration of 4% in all standards and test HPLC samples.
      A limit of quantitation (LOQ) as low as 20 ng/mL has been achieved for both
      compounds. This method can readily be adopted for the quantitative determination
      of other small molecules in concentrated protein solutions.

PMID- 21903217
TI  - Micelle to solvent stacking of organic cations in micellar electrokinetic
      chromatography with sodium dodecyl sulfate.
AB  - The on-line sample concentration technique, micelle to solvent stacking (MSS),
      was studied for small organic cations (quaternary ammonium herbicides, beta
      blocker drugs, and tricyclic antidepressant drugs) in reversed migration micellar
      electrokinetic chromatography. Electrokinetic chromatography was carried out in
      fused silica capillaries with a background solution of sodium dodecyl sulfate
      (SDS) in a low pH phosphate buffer. MSS was performed using anionic SDS micelles
      in the sample solution for analyte transport and methanol or acetonitrile as
      organic solvent in the background solution for analyte effective electrophoretic
      mobility reversal. The solvent also allowed for the separation of the analyte
      test mixtures. A model for focusing and separation was developed and the mobility
      reversal that involved micelle collapse was experimentally verified. The effect
      of analyte retention factor was observed by changing the % organic solvent in the
      background solution or the concentration of SDS in the sample matrix. With an
      injection length of 31.9 cm (77% of effective capillary length) for the 7 test
      drugs, the LODs (S/N=3) of 5-14 ng/mL were 101-346-fold better when compared to
      typical injection. The linearity (R(2), range=0.025-0.8 MUg/mL), intraday and
      interday repeatability (%RSD, n=10) were >=0.988, <6.0% and <8.5%, respectively.
      In addition, analysis of spiked urine samples after 10-fold dilution with the
      sample matrix yielded LODs=0.02-0.10 MUg/mL. These LODs are comparable to
      published electrophoretic methods that required off-line sample concentration.
      However, the practicality of the technique for more complex samples will rely on
      dedicated sample preparation schemes.

PMID- 21903218
TI  - Chitosan and silver nanoparticles as pudding with raisins with antimicrobial
      properties.
AB  - Chitosan nanoparticles (CS-NP) containing small silver nanoparticles are reported
      (Ag@CS-NP). CS-NP was synthesized using tripolyphosphate (TPP) as a polyanionic
      template. TPP also served to electrostatically attract Ag(+) inside CS-NP, where
      it was reduced by the terminal glucosamine units of the biopolymer. This
      procedure is environmental friendly, inexpensive, and permits the synthesis of
      very small AgNP (0.93-1.7 nm), with only a discrete dependence from the amount of
      silver nitrate used (5-200mg). The obtained hybrid nanocomposites Ag@CS-NP were
      characterized by DLS, HRTEM, and HAADF-STEM presenting a mean hydrodynamic
      diameter of 78 nm. The antimicrobial activity of Ag@CS-NP against Candida
      glabrata, Sacharomyces cerevisiae, Escherichia coli, Klebsiella pneumoniae,
      Salmonella, Staphylococcus aureus, and Bacillus cereus corresponded to MIC values
      lower than for AgNO(3).

PMID- 21903219
TI  - Excess thermodynamic properties of thin water films confined between
      hydrophobized gold surfaces.
AB  - Surface forces between gold surfaces were measured in pure water at temperatures
      in the range of 10-40  degrees C using an atomic force microscope (AFM). The
      surfaces were hydrophobized by self-assembly of alkanethiols (C(n)SH) with n=2
      and 16 in ethanol solutions. The data were used to determine the changes in
      excess free energies (DeltaG(f)) of the thin water films per unit area by using
      the Derjaguin approximation [1]. The free energy data were then used to determine
      the changes in excess film entropy (DeltaS(f)) and the excess film enthalpy
      (DeltaH(f)) per unit area. The results show that both DeltaS(f) and DeltaH(f)
      decrease with decreasing film thickness, suggesting that the macroscopic
      hydrophobic interaction involves building some kind of structures in the
      intervening thin films of water. It was found that |DeltaH(f)|>|TDeltaS(f)|,
      which is a necessary condition for an attractive force to appear when the
      enthalpy and entropy changes are both negative. That macroscopic hydrophobic
      interaction is enthalpically driven is contrary to the hydrophobic interactions
      at molecular scale. The results obtained in the present work are used to discuss
      possible origins for the long-range attractions observed between hydrophobic
      surfaces.

PMID- 21903220
TI  - Properties of beta-sitostanol/DPPC monolayers studied with Grazing Incidence X
      ray Diffraction (GIXD) and Brewster Angle Microscopy.
AB  - Although the influence of structurally modified sterols on artificial membranes
      has been intensively investigated, studies on the properties of stanols, which
      are saturated analogs of sterols, are very rare. Therefore, we have performed
      Grazing Incidence X-ray Diffraction (GIXD) experiments aimed at studying in-plane
      organization of a plant stanol-beta-sitostanol monolayer and its mixtures with
      1,2-dipalmitoyl-sn-glycero-3-phosphocholine - DPPC at the air/water interface.
      The collected GIXD data, resulting in-plane parameters and BAM images provide
      information on molecular organization and in-plane ordering of the investigated
      films. It was found that the lateral organization of beta-sitostanol/DPPC
      monolayers depends on their composition. The oblique structure of the in-plane
      lattice of tilted hydrophobic region of molecules, found for DPPC film, is
      maintained at 10 mol% of stanol in the system. However, at 30 and 90 mol% of
      stanol in the mixture, the arrangement of molecules is hexagonal and they are
      oriented perpendicularly to the interface. With the addition of stanol the extend
      of the in-plane order of the monolayers decreases. Moreover, in mixtures the
      ordered domains consist of both monolayer's components. Additionally, beta
      sitostanol film is of similar in-plane organization as the corresponding sterol
      monolayer (beta-sitosterol) and stanol induces condensing effect on DPPC.

PMID- 21903221
TI  - Self-assembly of pH-sensitive mixed micelles based on linear and star copolymers
      for drug delivery.
AB  - Comicellization of a star block copolymer poly(epsilon-caprolactone)-block
      poly(diethylamino)ethyl methacrylate (S(PCL-b-PDEAEMA)) and a linear block
      copolymer methoxy poly(ethylene glycol)-block-poly(epsilon-caprolactone) (mPEG-b
      PCL) was developed to enhance the stability and lower the cytotoxicity of the
      micelles. The two copolymers self-assembled into the mixed micelles with a common
      PCL core surrounded by a mixed PDEAEMA/mPEG shell in aqueous solution. This core
      shell structure was transformed to the core-shell-corona structure at high pH due
      to the collapse of the PDEAEMA segment. The properties of the polymeric micelles
      were greatly dependent on the weight ratio of the two copolymers and the external
      pH. As increasing the mPEG-b-PCL content, the size and the zeta potential of the
      mixed micelles were lowered while the pH-dependent stability and the
      biocompatibility were improved. Moreover, an increase in pH accelerated the
      release of indomethacin (IND) from the mixed micelles in vitro. These results
      augured that the mixed micelles could be applied as a stable pH-sensitive release
      system.

PMID- 21903222
TI  - Synthesis of transparent aqueous sols of colloidal layered niobate nanocrystals
      at room temperature.
AB  - Transparent aqueous sols of colloidal tetramethylammonium niobate nanocrystals
      were synthesized by mixing tetramethylammonium hydroxide (TMAOH), niobium
      ethoxide, and water at TMAOH/Nb>=0.7 at room temperature. The X-ray diffraction
      patterns of the thin films prepared by evaporating the colloidal solutions on a
      glass substrate indicated that the colloidal niobate had a layered crystalline
      structure. Two types of layered structures are known as a layered niobate, i.e.
      M(4)Nb(6)O(17).nH(2)O and MNb(3)O(8) (M=H, H(3)O, or alkaline metal). Raman
      spectra and electron diffraction suggested that the niobate nanocrystals were
      similar in crystal structure to M(4)Nb(6)O(17).nH(2)O compounds. Moreover, when
      niobium oxide thin films were fabricated from the niobate colloidal solutions by
      the sol-gel method, oriented T-Nb(2)O(5) thin films, whose c-axis was parallel to
      the substrate surface, were obtained. The orientation of the thin films was
      probably attributed to the layered structure of the colloidal niobate
      nanocrystals.

PMID- 21903223
TI  - Linguistic labels: conceptual markers or object features?
AB  - Linguistic labels affect inductive generalization; however, the mechanism
      underlying these effects remains unclear. According to one similarity-based
      model, SINC (similarity, induction, naming, and categorization), early in
      development labels are features of objects contributing to the overall similarity
      of compared entities, with early induction being similarity based. If this is the
      case, then not only identical but also phonologically similar labels may
      contribute to the overall similarity and thus to induction. These predictions
      were tested in a series of experiments with 5-year-olds and adults. In
      Experiments 1-5 participants performed a label extension task, whereas in
      Experiment 6 they performed a feature induction task. Results indicate that
      phonological similarity contributes to early induction and support the notion
      that for young children labels are features of objects.

PMID- 21903225
TI  - Implantation of a centrifugal pump as a left ventricular assist device through a
      novel, minimized approach: upper hemisternotomy combined with anterolateral
      thoracotomy.

PMID- 21903224
TI  - An examination of the relation between conduct disorder, childhood and adulthood
      traumatic events, and posttraumatic stress disorder in a nationally
      representative sample.
AB  - BACKGROUND: Clinical data has indicated that exposure to trauma and meeting
      diagnostic criteria for posttraumatic stress disorder (PTSD) are common among
      individuals with a history of conduct disorder. However, these relationships have
      not been adequately examined in a population-based sample. METHODS: Data were
      drawn from Wave 2 of the U.S. National Epidemiologic Survey on Alcohol and
      Related Conditions (NESARC) collected in 2004-2005 (n = 34,653, response rate =
      86.7%). Multivariate logistic regression analyses were conducted to examine
      relations between conduct disorder, traumatic life events, and PTSD in the full
      sample, and separately for males and females. RESULTS: The main findings indicate
      that childhood maltreatment was associated with conduct disorder (Adjusted Odds
      Ratio [AOR] ranging from 2.4 to 4.7) after adjustment for sociodemographic
      variables. Additionally, respondents with a history of conduct disorder compared
      to respondents without conduct disorder were more likely to report experiencing
      any traumatic event (AOR = 2.7, 95% CI = 2.0-3.6) and PTSD (AOR = 2.2, 95% CI =
      1.8-2.7) after adjusting for sociodemographic variables. Although sex differences
      were noted, conduct disorder was associated with the greatest odds of assaultive
      violence for males and females. The majority of individuals (72.9%) diagnosed
      with both conduct disorder and PTSD developed conduct disorder symptoms before
      PTSD symptoms. CONCLUSIONS: Results of this study provide the first known sex
      stratified examination of the relationship between conduct disorder, traumatic
      events, and PTSD in a large, population-based sample of adults and are consistent
      with clinical impressions. Policy and clinical implications are discussed.

PMID- 21903226
TI  - Metal (Al, Fe, Mn and Cu) distributions and origins of polycyclic aromatic
      hydrocarbons (PAHs) in the surface sediments of the Marmara Sea and the coast of
      Istanbul, Turkey.
AB  - In this study, total metal (Al, Fe, Mn and Cu) and PAHs analyses have been done
      in the surface sediments. Sediment samples have been collected from seven parts
      of the Marmara Sea and the coast of Istanbul during 2009. Total Al, Fe, Mn and Cu
      contents vary between 1.8% and 5.4%; 1.1% and 2.8%; 122 and 259 MUg g(-1); 27 and
      416 MUg g(-1), respectively. EF and CF values of Fe and Mn are lower than 1.5 and
      1, respectively, in all the stations. Total PAH contents range between 135 and
      6009 ng g(-1) in the surface sediments. The origin of PAHs has been found
      pyrolitic according to the Phe/Ant ratio in the all stations. Contrastingly, at
      K0, MKC and MY1 Stations, PAH origins have been observed petrogenic according to
      the Flu/Pyr ratio.

PMID- 21903227
TI  - Ostreopsis cf. ovata bloom in the northern Adriatic Sea during summer 2009:
      ecology, molecular characterization and toxin profile.
AB  - Intense blooms of the benthic dinoflagellate Ostreopsis cf. ovata have occurred
      in the northern Adriatic Sea since 2006. These blooms are associated with noxious
      effects on human health and with the mortality of benthic organisms because of
      the production of palytoxin-like compounds. The O. cf. ovata bloom and its
      relationships with nutrient concentrations at two stations on the Conero Riviera
      (northern Adriatic Sea) were investigated in the summer of 2009. O. cf. ovata
      developed from August to November, with the highest abundances in September
      (1.3*10(6) cells g(-1) fw corresponding to 63.8*10(3) cells cm(-2)). The presence
      of the single O. cf. ovata genotype was confirmed by a PCR assay. Bloom developed
      when the seawater temperature was decreasing. Nutrient concentrations did not
      seem to affect bloom dynamics. Toxin analysis performed by high resolution liquid
      chromatography-mass spectrometry revealed a high total toxin content (up to 75 pg
      cell(-1)), including putative palytoxin and all the ovatoxins known so far.

PMID- 21903228
TI  - Trace metals in sediment cores from Deception and Penguin Islands (South Shetland
      Islands, Antarctica).
AB  - This paper presents information on the levels of trace elements in sediments
      collected at Deception and Penguin Islands and tracks the sources of natural and
      anthropogenic inputs of metals into this sub-Antarctic region. The results
      suggest that natural processes, such as volcanic activity, hydrothermal processes
      and sediment transport, are more important than anthropogenic inputs in
      accounting for the metal concentrations measured in sediments at Deception
      Island. The higher levels of trace metals recorded in sediments at Penguin Island
      seem to reflect the composition of the source rocks of the island, which are
      dominated by the olivine-basalt group. Our findings show that human activities in
      the study areas may contribute to negligible levels of trace metals associated
      with anthropogenic inputs (e.g., Cr and Zn) in sediments, and these results can
      be used in the future as background levels related to low anthropogenic impacts.

PMID- 21903229
TI  - Who, when, and how? Marine planning stakeholder involvement preferences--a case
      study of the Solent, United Kingdom.
AB  - The introduction of a marine planning system throughout English territorial
      waters over the next decade provides an opportunity for stakeholder input to the
      management of the marine environment. Stakeholder involvement has been identified
      as an important component of successful development and subsequent implementation
      of marine planning but it has to be recognised that the views and interest of
      stakeholders can vary greatly, thus the desire for involvement with the process
      is unlikely to be uniform. This paper presents the views of stakeholders within
      the Solent, United Kingdom on their potential involvement with the marine
      planning process. Interestingly, it highlights a strong variability of views
      within and across sectors. Assuming the situation in the Solent is typical of
      groups of stakeholders throughout the country, the lack of uniformity in the
      potential involvement from different stakeholders may present a challenge in
      achieving a representative and truly collaborative marine planning process.

PMID- 21903230
TI  - The blue anthocyanin pigments from the blue flowers of Heliophila coronopifolia
      L. (Brassicaceae).
AB  - Six acylated delphinidin glycosides (pigments 1-6) and one acylated kaempferol
      glycoside (pigment 9) were isolated from the blue flowers of cape stock
      (Heliophila coronopifolia) in Brassicaceae along with two known acylated cyanidin
      glycosides (pigments 7 and 8). Pigments 1-8, based on 3-sambubioside-5-glucosides
      of delphinidin and cyanidin, were acylated with hydroxycinnamic acids at 3
      glycosyl residues of anthocyanidins. Using spectroscopic and chemical methods,
      the structures of pigments 1, 2, 5, and 6 were determined to be: delphinidin 3-O
      [2-O-(beta-xylopyranosyl)-6-O-(acyl)-beta-glucopyranoside]-5-O-[6-O-(malonyl)
      beta-glucopyranoside], in which acyl moieties were, respectively, cis-p-coumaric
      acid for pigment 1, trans-caffeic acid for pigment 2, trans-p-coumaric acid for
      pigment 5 (a main pigment) and trans-ferulic acid for pigment 6, respectively.
      Moreover, the structure of pigments 3 and 4 were elucidated, respectively, as a
      demalonyl pigment 5 and a demalonyl pigment 6. Two known anthocyanins (pigments 7
      and 8) were identified to be cyanidin 3-(6-p-coumaroyl-sambubioside)-5-(6-malonyl
      glucoside) for pigment 7 and cyanidin 3-(6-feruloyl-sambubioside)-5-(6-malonyl
      glucoside) for pigment 8 as minor anthocyanin pigments. A flavonol pigment
      (pigment 9) was isolated from its flowers and determined to be kaempferol 3-O-[6
      O-(trans-feruloyl)-beta-glucopyranoside]-7-O-cellobioside-4'-O-glucopyranoside as
      the main flavonol pigment. On the visible absorption spectral curve of the fresh
      blue petals of this plant and its petal pressed juice in the pH 5.0 buffer
      solution, three characteristic absorption maxima were observed at 546, 583 and
      635 nm. However, the absorption curve of pigment 5 (a main anthocyanin in its
      flower) exhibited only one maximum at 569 nm in the pH 5.0 buffer solution, and
      violet color. The color of pigment 5 was observed to be very unstable in the pH
      5.0 solution and soon decayed. In the pH 5.0 solution, the violet color of
      pigment 5 was restored as pure blue color by addition of pigment 9 (a main
      flavonol in this flower) like its fresh flower, and its blue solution exhibited
      the same three maxima at 546, 583 and 635 nm. On the other hand, the violet color
      of pigment 5 in the pH 5.0 buffer solution was not restored as pure blue color by
      addition of deacyl pigment 9 or rutin (a typical flower copigment). It is
      particularly interesting that, a blue anthocyanin-flavonol complex was extracted
      from the blue flowers of this plant with H(2)O or 5% HOAc solution as a dark blue
      powder. This complex exhibited the same absorption maxima at 546, 583 and 635 nm
      in the pH 5.0 buffer solution. Analysis of FAB mass measurement established that
      this blue anthocyanin-flavonol complex was composed of one molecule each of
      pigment 5 and pigment 9, exhibiting a molecular ion [M+1] (+) at 2102 m/z
      (C(93)H(105)O(55) calc. 2101.542). However, this blue complex is extremely
      unstable in acid solution. It really dissociates into pigment 5 and pigment 9.

PMID- 21903231
TI  - Lagunamide C, a cytotoxic cyclodepsipeptide from the marine cyanobacterium
      Lyngbya majuscula.
AB  - Lagunamide C (1) is a cytotoxic cyclodepsipeptide isolated from the marine
      cyanobacterium, Lyngbya majuscula, from the western lagoon of Pulau Hantu Besar,
      Singapore. The complete structural characterization of the molecule was achieved
      by extensive NMR spectroscopic analysis as well as chemical manipulations.
      Several methods, including the advanced Marfey's method, a modified method based
      on derivatization with Mosher's reagents and analysis using LC-MS, and the use of
      (3)J(H-H) coupling constant values, were utilized for the determination of its
      absolute configuration. Compound 1 is related to the aurilide-class of molecules
      and it differs mainly in the macrocyclic structure by having a 27 membered ring
      system due to additional methylene carbon in the polyketide moiety. Lagunamide C
      displayed potent cytotoxic activity against a panel of cancer cell lines, such as
      P388, A549, PC3, HCT8, and SK-OV3 cell lines, with IC(50) values ranging from 2.1
      nM to 24.4 nM. Compound 1 also displayed significant antimalarial activity with
      IC(50) value of 0.29 MUM when tested against Plasmodium falciparum. In addition,
      lagunamide C exhibited weak anti-swarming activity when tested at 100 ppm against
      the Gram-negative bacterial strain, Pseudomonas aeruginosa PA01.

PMID- 21903232
TI  - Limonoids from the stems of Toona ciliata var. henryi (Meliaceae).
AB  - Ten limonoids, toonacilianins A-J, and two norlimonoids, toonacilianins K and L,
      together with seven known compounds were isolated from the stems of Toona ciliata
      var. henryi (Meliaceae). Their structures were elucidated by spectroscopic
      analysis. Two compounds showed strong cytotoxic activities.

PMID- 21903233
TI  - Supportive care in neurooncology.
AB  - The quality of life of patients treated for brain tumor is, in all cases, deeply
      altered by the tumor and the treatments. Optimizing the symptomatic management is
      a key objective for all care givers. We present in this paper a very pragmatic
      focus concerning the management of intracranial hypertension (and/or neurological
      deficits), venous thromboembolism, confusion, epilepsy and symptoms more directly
      associated with the end of life.

PMID- 21903234
TI  - Extent of resection influences outcomes for patients with gliomas.
AB  - In recent years, advances in our understanding of the biology of low-grade
      gliomas (LGG) and high-grade gliomas (HGG) have driven new paradigms in molecular
      markers, diagnostic imaging, operative techniques and technologies, and adjuvant
      therapies. Taken together, these developments are collectively pushing the
      envelope towards improved quality of life and survival. Here, we review the
      recent literature to synthesize a comprehensive review of the value of extent of
      resection for LGGs and HGGs in the modern neurosurgical era.

PMID- 21903235
TI  - [Multimodal magnetic resonance imaging of brain tumors].
AB  - Magnetic resonance imaging arose as a reference for diagnosis, pre-therapeutic
      and follow-up of brain tumors. Among parameters obtained from standard MRI (of
      low specificity), only volumetric growth allows prognostic information. The
      multiple "advanced" sequences have leaded to increase both sensitivity and
      specificity of brain MRI. Yet, perfusion-weighted imaging and spectroscopy
      provide metabolic information, and diffusion tensor imaging and cortical
      activation provide functional information. Characterization, grading, therapeutic
      management and follow-up have improved, with prognostic information.

PMID- 21903236
TI  - Fate of N-nitrosodimethylamine, trihalomethane and haloacetic acid precursors in
      tertiary treatment including biofiltration.
AB  - The presence of disinfection by-products (DBPs) such as trihalomethanes (THMs),
      haloacetic acids (HAAs) and N-nitrosamines in water is of great concern due to
      their adverse effects on human health. In this work, the removal of N
      nitrosodimethylamine (NDMA), total THM and five HAA precursors from secondary
      effluent by biological activated carbon (BAC) is investigated at full and pilot
      scale. In the pilot plant two filter media, sand and granular activated carbon,
      are tested. In addition, we evaluate the influence of ozonation prior to BAC
      filtration on its performance. Among the bulk of NDMA precursors, the fate of
      four pharmaceuticals containing a dimethylamino moiety in the chemical structure
      are individually investigated. Both NDMA formation potential and each of the
      studied pharmaceuticals are dramatically reduced by the BAC even in the absence
      of main ozonation prior to the filtration. The low removal of NDMA precursors at
      the sand filtration in comparison to the removal of NDMA precursors at the BAC
      suggests that adsorption may play an important role on the removal of NDMA
      precursors by BAC. Contrary, the precursors for THM and HAA formation are reduced
      in both sand filtration and BAC indicating that the precursors for the formation
      of these DBPs are to some extent biodegradable.

PMID- 21903237
TI  - Phytoaccumulation of antimicrobials from biosolids: impacts on environmental fate
      and relevance to human exposure.
AB  - Triclocarban and triclosan, two antimicrobials widely used in consumer products,
      can adversely affect ecosystems and potentially impact human health. The
      application of biosolids to agricultural fields introduces triclocarban and
      triclosan to soil and water resources. This research examined the
      phytoaccumulation of antimicrobials, effects of plant growth on migration of
      antimicrobials to water resources, and relevance of phytoaccumulation in human
      exposure to antimicrobials. Pumpkin, zucchini, and switch grass were grown in
      soil columns to which biosolids were applied. Leachate from soil columns was
      assessed every other week for triclocarban and triclosan. At the end of the
      trial, concentrations of triclocarban and triclosan were determined for soil,
      roots, stems, and leaves. Results indicated that plants can reduce leaching of
      antimicrobials to water resources. Pumpkin and zucchini growth significantly
      reduced soil concentrations of triclosan to less than 0.001 mg/kg, while zucchini
      significantly reduced soil concentrations of triclocarban to 0.04 mg/kg. Pumpkin,
      zucchini, and switch grass accumulated triclocarban and triclosan in mg per kg
      (dry) concentrations. Potential human exposure to triclocarban from consumption
      of pumpkin or zucchini was substantially less than exposure from product use, but
      was greater than exposure from drinking water consumption. Consequently, research
      indicated that pumpkin and zucchini may beneficially impact the fate of
      antimicrobials in agricultural fields, while presenting minimal acute risk to
      human health.

PMID- 21903238
TI  - NDMA formation kinetics from three pharmaceuticals in four water matrices.
AB  - N, N-nitrosodimethylamine (NDMA) is an emerging disinfection by-product (DBP)
      that has been widely detected in many drinking water systems and commonly
      associated with the chloramine disinfection process. Some amine-based
      pharmaceuticals have been demonstrated to form NDMA during chloramination, but
      studies regarding the reaction kinetics are largely lacking. This study
      investigates the NDMA formation kinetics from ranitidine, chlorphenamine, and
      doxylamine under practical chloramine disinfection conditions. The formation
      profile was monitored in both lab-grade water and real water matrices, and a
      statistical model is proposed to describe and predict the NDMA formation from
      selected pharmaceuticals in various water matrices. The results indicate the
      significant impact of water matrix components and reaction time on the NDMA
      formation from selected pharmaceuticals, and provide fresh insights on the
      estimation of ultimate NDMA formation potential from pharmaceutical precursors.

PMID- 21903239
TI  - Chemical extractions and predicted free ion activities fail to estimate metal
      transfer from soil to field land snails.
AB  - This study investigates the relevance of several soil chemical extractions
      (calcium chloride, acetic acid, citric acid and a four-step sequential procedure)
      and predicted free metal ion activities in the soil solution to characterise the
      transfer of trace metals (Cd, Pb, and Zn) from soil to snail soft tissues over a
      large smelter-impacted area (Metaleurop Nord, Nord-Pas-de-Calais, France). The
      study was first performed on six snail species together and then specifically on
      Cepaea sp. and Oxychilus draparnaudi. When the six species were considered
      together, the accumulation of metals depended mostly on the species. When
      significant, total or extractable metal concentrations, or the predicted free ion
      activities, accounted for less than 7% of the variation of the metal
      concentrations in the snail tissues. Species-specific analyses showed that
      extractable concentrations explained approximately 25% of the variation of the
      metal concentrations in O. draparnaudi, and up to 8% in Cepaea snails. When using
      total soil concentrations and soil properties as explanatory variables, the
      models were generally slightly better, explaining up to 42% of the variance. The
      soil extraction procedures and predicted free ion activities used in this study
      did not accurately estimate the metal transfer from soil to snails and could not
      be used in risk assessment.

PMID- 21903241
TI  - Counterbalancing effects of maternal mercury exposure during different stages of
      early ontogeny in American toads.
AB  - Maternal transfer of environmental contaminants is a disadvantageous parental
      effect which can have long-lasting implications for offspring fitness. We
      investigated the effects of mercury (Hg) on the reproductive success of female
      amphibians and the subsequent effects of maternal transfer on the development of
      their offspring. American toads (Bufo americanus) maternally transferred Hg to
      their eggs, and there was a negative relationship between Hg concentrations and
      the percentage of viable hatchlings produced in clutches. However, when we
      continued to monitor larvae that successfully hatched, we found 21% greater
      metamorphic success in larvae from Hg-exposed mothers compared to reference
      larvae. The negative effect in the embryonic stage and positive effect in the
      larval stage counterbalanced one another, ultimately resulting in no difference
      in predicted terrestrial recruitment, regardless of maternal Hg exposure. Our
      findings demonstrate that maternal effects on survival manifesting at different
      stages in ontogeny have the potential to produce complicated outcomes.

PMID- 21903240
TI  - Urea: An important piece of Water Soluble Organic Nitrogen (WSON) over the
      Eastern Mediterranean.
AB  - The role of atmospheric urea on the biogeochemical cycle of Water Soluble Organic
      Nitrogen (WSON) in the Eastern Mediterranean was assessed by collecting and
      analyzing wet and dry deposition samples and size segregated aerosols during a
      one year period (2006). In rain water volume weighted mean (VWM) concentration of
      urea was found equal to 5.5MUM. In atmospheric particles the average
      concentration of urea in coarse and fine mode was 0.9+/-1.9nmol N m(-3) (median
      0.0nmol N m(-3)) and 2.2+/-3.0nmol N m(-3) (median 1.1nmol N m(-3)),
      respectively. The percentage contribution of urea to WSON fraction was 0% and 20%
      in coarse and fine particles respectively. On an annual basis 0.81mmol m(-2) and
      1.78mmol m(-2) of urea were deposited via wet and dry deposition, contributing to
      WSON by 10% and 11% respectively. Regression analysis of urea with the main ions
      and trace metals measured in parallel suggest that soil and anthropogenic
      activities significantly contribute to atmospheric urea. Comparison of dry
      deposition of urea using size segregated deposition velocities with urea
      collected on a glass bead collector suggested the existence of significant
      fraction of urea in the gas phase.

PMID- 21903242
TI  - The endothelial cell protein C receptor: its role in thrombosis.
AB  - The protein C anticoagulant pathway plays a crucial role as a regulator of the
      blood clotting cascade. Protein C is activated on the vascular endothelial cell
      membrane by the thrombin-thrombomodulin complex. The endothelial protein C
      receptor binds protein C and further enhances protein C activation. Once formed,
      activated protein C down-regulates thrombin formation by inactivating factors Va
      and VIIIa and exerts cytoprotective effects through endothelial protein C
      receptor binding. An adequate generation of activated protein C depends on the
      precise assembly, on the surface of the endothelial cells, of thrombin,
      thrombomodulin, protein C, and endothelial protein C receptor. Therefore, any
      change in the efficiency of this assembly may cause a reduction or increase in
      activated protein C generation and modulate the risk of thrombosis. This review
      highlights the role of the endothelial protein C receptor in disease and
      discusses the association of its mutations with the risk of thrombosis.

PMID- 21903243
TI  - Outcomes and clinicopathologic variables associated with late recurrence after
      nephrectomy for localized renal cell carcinoma.
AB  - OBJECTIVE: To characterize the incidence and clinicopathologic factors associated
      with late recurrence after surgical resection for renal cell carcinoma (RCC)
      because the recurrence patterns >5 years after nephrectomy have been poorly
      described. METHODS: We identified 1454 patients treated with nephrectomy for
      localized RCC from 1970 to 2000 who had remained free of disease for 5 years.
      Subsequent tumor recurrence was classified as renal recurrence and distant
      metastasis. The incidence of recurrence >5 years from surgery was estimated using
      the Kaplan-Meier method. The associations of clinicopathologic variables with
      late recurrence were analyzed using Cox proportional hazard regression models.
      RESULTS: With a median postoperative follow-up of 13.9 years (range 5.1-38.9), 63
      patients (4.3%) experienced late renal recurrence at a median of 9.3 years (range
      5.1-25.3), and 172 patients (11.8%) developed late distant metastases at a median
      of 9.6 years (range 5.1-26.6) after surgery. The estimated recurrence-free
      survival rate at 10 and 15 years was 97.3% and 95.2% for renal recurrence, and
      93.1% and 85.9% for distant metastases, respectively. On multivariate analysis,
      increased tumor size (hazard ratio [HR] 1.12; P < .001) was associated with late
      renal tumor recurrence, and increased tumor size (HR 1.07; P = .018), clear cell
      or collecting duct histologic features (HR 3.76; P < .001), and tumor Stage pT1b
      (HR 2.8; P < .001), pT2a (HR 4.5; P < .001), pT2b (HR 3.4; P = .007), and pT3-pT4
      (HR 5.1; P < .001) were associated with distant metastasis. CONCLUSION: After an
      initial 5-year postoperative disease-free interval, approximately 5% and 15% of
      patients will develop renal recurrence and distant metastases, respectively,
      during the next decade. Therefore, long-term surveillance remains necessary after
      nephrectomy.

PMID- 21903244
TI  - Parental perception of optimal surgical age for correction of cryptorchidism: a
      multicenter surveillance study.
AB  - OBJECTIVE: To perform a multicenter survey to determine how many parents
      understood the optimal time for surgical correction of cryptorchidism in
      children. METHODS: We enrolled 377 parents of patients who had recently undergone
      surgical correction of cryptorchidism. These parents were divided into 3 groups
      according to their indicated preference of the optimal patient age for surgical
      correction: group 1 (<1 year old, 39 parents, 10.3%), group 2 (1-2 years old, 169
      parents, 44.8%), and group 3 (>3 years, 169 parents, 44.8%). RESULTS: The mean
      age of the children who underwent orchiopexy was 4.9 +/- 5.2 years. The interval
      from diagnosis to surgical correction of cryptorchidism was 17.1 +/- 29.8, 15.4
      +/- 14.4, and 29.0 +/- 24.4 months in groups 1, 2, and 3, respectively (P <
      .001). The mean age of the parents was significantly associated with the
      perception of the optimal time for surgical correction of cryptorchidism (P =
      .021 and P = .002). The number of highly educated parents was lowest in group 3
      (P < .001). The number of parents with >2 children was 69.2% in group 1, 71.0% in
      group 2, and 84.0% in group 3 (P = .009). In group 3, the parents often delayed
      surgery because of the patient being too young (49.1%) and the parents'
      expectations of spontaneous descent (48.5%). CONCLUSION: Parents younger in age,
      with higher education levels and with fewer children, preferred early orchiopexy.
      Active intervention by a physician and public education for parents might be
      necessary to encourage earlier treatment of cryptorchidism.

PMID- 21903245
TI  - Stopping anticoagulation before TURP does not appear to increase perioperative
      cardiovascular complications.
AB  - OBJECTIVE: To evaluate the impact of stopping anticoagulant medications prior to
      transurethral resection of the prostate on peri-operative cardiovascular
      complications. METHODS: Retrospective series (305 patients) undergoing TURP at a
      tertiary hospital between 2006 and 2010. All men were evaluated in preadmission
      clinics with defined protocols, with a low threshold for cardiovascular
      investigation. Incidence of postoperative bleeding and cardiovascular and
      cerebrovascular events was determined for 3 patient cohorts: group A--where
      anticoagulants were ceased preoperatively; group B--who were not receiving any
      anticoagulants; and group C--who underwent TURP while taking aspirin. RESULTS: Of
      305 patients, 194 (64%) did not receive anticoagulation therapy, 108 (35%)
      stopped receiving anticoagulation therapy pre-TURP, and 3 (0.98%) underwent TURP
      while taking aspirin. Anticoagulants used were aspirin (22.6%), warfarin (4.9%),
      antiplatelets (4.9%), and combination treatments (3.9%). Incidence of
      postoperative hemorrhage (early and delayed) was not significant (P = .69)
      between group A (10/108) and group B (7/194). Transfusion rate was 0.6% (2/305).
      Overall incidence of cardiovascular events was 0.98% (group A, n = 1 vs group B,
      n = 2), and incidence of deep vein thrombosis (0.32%; group A, n = 0 vs group B,
      n = 1) was not statistically significant (P = .30 and P = .37, respectively).
      Overall incidence of cerebrovascular events (0.65%; group A, n = 1 vs group B, n
      = 1) was not significant (P = 1.00). There were no deaths. CONCLUSION: Men who
      have discontinue anticoagulation therapy before TURP do not appear to have a
      higher incidence of cardiovascular or cerebrovascular events, or bleeding
      associated morbidity. It is possible that the morbidity attributed to
      discontinuing anticoagulation in this population may be overemphasized. Larger
      prospective studies are needed to better evaluate this clinical problem.

PMID- 21903246
TI  - The regulation of MASPIN expression in epithelial ovarian cancer: association
      with p53 status, and MASPIN promoter methylation: a gynecologic oncology group
      study.
AB  - OBJECTIVES: To elucidate the regulation of MASPIN expression in epithelial
      ovarian cancer (EOC) and associations with p53 status and MASPIN promoter
      methylation. METHODS: Seven EOC cell lines and 110 advanced stage EOC specimens
      were analyzed for MASPIN promoter methylation. The cell lines were treated with 5
      azacytidine (5-azaC) and evaluated for MASPIN promoter methylation, protein, and
      mRNA expression. Wild-type (wt) p53 was transiently transfected into the mutant
      p53 (m p53) SKOV3 cells which were treated with 5-azaC. Phosphor imager analysis
      quantified the percent methylation of the MASPIN promoter. RESULTS: Of the 3
      MASPIN-low m p53 cell lines 2 had greater than 5% MASPIN methylation whereas only
      1 of 4 MASPIN-high wt p53 cell lines had greater than 5% MASPIN methylation.
      Despite the presence of aberrant MASPIN promoter methylation in SKOV3 cells, wt
      p53-transfection alone resulted in a 3.3-fold increase in MASPIN mRNA. The
      combination of 5-azaC and wt p53-transfection produced a 36% reduction in MASPIN
      promoter methylation and 4.5-fold increase in MASPIN transcription. Among the 110
      ovarian cancer specimens analyzed for methylation of the MASPIN promoter, 81.8%
      were weakly methylated, 14.5% were heavily methylated and 3.6% were fully
      methylated. There was no relationship between promoter methylation and p53 status
      or MASPIN protein expression. However, MASPIN protein was 6 times more likely to
      be detected in cancer specimens that harbor a p53 mutation relative to cancer
      specimens with a wt p53 gene. CONCLUSION: The regulation of MASPIN is a complex
      multifactorial process that may be controlled by both p53-dependent and 
      independent epigenetic mechanisms.

PMID- 21903247
TI  - The role of the phosphatidylinositol 3-kinase (PI3K) pathway in the development
      and treatment of uterine cancer.
AB  - OBJECTIVE: Uterine cancer is the most common gynecologic malignancy in the United
      States. Although surgery is often curative for women diagnosed in the early
      stages, prognosis for patients with advanced disease is poor. Alterations in the
      phosphatidylinositol 3-kinase (PI3K) pathway are known to play a significant role
      in the development of uterine cancer and provide a possible target for new
      therapies. METHODS: PubMed was searched for articles of relevance to uterine
      cancer and the PI3K pathway. In addition, abstracts from key oncology congresses
      were scanned for data on novel therapeutic agents targeting the PI3K pathway.
      RESULTS: The PI3K pathway is an important promoter of cellular growth,
      metabolism, differentiation, proliferation, survival, and angiogenesis. It is
      often upregulated in uterine cancer, with the most frequent genetic alterations
      occurring in phosphatase and tensin homolog (PTEN), PIK3CA, and KRAS.
      Deregulation of the pathway has been associated with resistance to hormonal
      therapy and chemotherapy. Inhibitors of the PI3K pathway are in clinical testing
      in patients with solid tumors, including uterine cancer. Results with monotherapy
      demonstrate some clinical responses, but mainly as prolonged stable disease. PI3K
      pathway inhibitors are currently being evaluated in patients with tumors in which
      the PI3K pathway is deregulated. Another strategy being evaluated is the ability
      of PI3K pathway inhibitors to restore sensitivity to standard therapy.
      CONCLUSIONS: Investigational PI3K pathway inhibitors represent a promising new
      therapeutic strategy in uterine cancer. Exploration of effective drug
      combinations and their applicability to individual tumors will be important in
      the future clinical development of these agents.

PMID- 21903248
TI  - Independent external validation of radiotherapy and its impact on the accuracy of
      a nomogram for predicting survival of women with endometrial cancer.
AB  - OBJECTIVE: To externally validate and assess the impact of radiotherapy on the
      accuracy of a nomogram for predicting overall survival of women with endometrial
      cancer. METHODS: Using data from the Surveillance, Epidemiology, and End Results
      (SEER), we assessed the concordance indexes, the discrimination and the
      calibration provided by a nomogram for predicting overall survival. Patients were
      grouped into deciles based on their survival predictions, and the three-year
      overall survival in each group was compared with the mean predicted probability.
      RESULTS: Between 1988 and 2006, 64,023 patients were analyzed and divided into
      two groups: 14,323 patients with adjuvant radiotherapy and 49,700 patients
      without adjuvant radiotherapy. Among the whole population, predicted and observed
      three-year overall survivals were 85.2% and 85.6% (+/-0.1%) respectively. In
      patients with adjuvant radiotherapy, overall survivals were 81.0% and 83.1% (+/
      0.3%) and in patients without adjuvant radiotherapy, they were 86.5% and 86.3%
      (+/-0.2%) respectively. The concordance indexes for the whole population, in
      patients with radiotherapy and in patients without radiotherapy were 0.811 (+/
      0.004), 0.751 (+/-0.009) and 0.803 (+/-0.006) respectively. The mean and maximal
      errors in patients with radiotherapy were 2.1% and 4.0% and in patients without
      radiotherapy 2.3% and 8.1%. CONCLUSIONS: The nomogram can accurately predict
      three-year overall survival, whether patients undergo adjuvant radiotherapy or
      not. The nomogram has an improved individual discrimination when compared with
      the 1988 and the 2009 staging systems for endometrial cancer. It may be useful in
      the information processed for patients and in building surveillance timing.

PMID- 21903249
TI  - Exosomes from ovarian cancer cells induce adipose tissue-derived mesenchymal stem
      cells to acquire the physical and functional characteristics of tumor-supporting
      myofibroblasts.
AB  - OBJECTIVE: Most tumor tissue is composed of parenchymal tumor cells and tumor
      stroma. Mesenchymal stem cells (MSCs) can function as precursors for tumor
      stromal cells, including myofibroblasts, which provide a favorable environment
      for tumor progression. A close relationship between tumor cells and MSCs in a
      tumor microenvironment has been described. Exosomes are small membrane vesicles
      that are enriched with a discrete set of cellular proteins, and are therefore
      expected to exert diverse biological functions according to cell origin. METHODS:
      In the current study, we determined the biological effect of exosomes from two
      ovarian cancer cell lines (SK-OV-3 and OVCAR-3) on adipose tissue-derived MSCs
      (ADSCs). RESULTS: Exosome treatment induced ADSCs to exhibit the typical
      characteristics of tumor-associated myofibroblasts, with increased expression of
      alpha-SMA, and also increased expression of tumor-promoting factors (SDF-1 and
      TGF-beta). This phenomenon was correlated with an increased expression of TGF
      beta receptors I and II. Analysis of TGF-beta receptor-mediated downstream
      signaling pathways revealed that each exosome activated different signaling
      pathways, showing that exosomes from SK-OV-3 cells increased the phosphorylated
      form of SMAD2, which is essential in the SMAD-dependent pathway, whereas exosomes
      from OVCAR-3 cells increased the phosphorylated form of AKT, a representative
      SMAD-independent pathway. Taken together, exosomes from ovarian cancer cells
      induced the myofibroblastic phenotype and functionality in ADSCs by activating an
      intracellular signaling pathway, although the activated pathway could differ from
      exosome-to-exosome. CONCLUSION: The current study suggested that ovarian cancer
      derived exosomes contribute to the generation of tumor-associated myofibroblasts
      from MSCs in tumor stroma.

PMID- 21903250
TI  - Does silent reading speed in normal adult readers depend on early visual
      processes? evidence from event-related brain potentials.
AB  - Little is known about the relationship of reading speed and early visual
      processes in normal readers. Here we examined the association of the early P1,
      N170 and late N1 component in visual event-related potentials (ERPs) with silent
      reading speed and a number of additional cognitive skills in a sample of 52 adult
      German readers utilizing a Lexical Decision Task (LDT) and a Face Decision Task
      (FDT). Amplitudes of the N170 component in the LDT but, interestingly, also in
      the FDT correlated with behavioral tests measuring silent reading speed. We
      suggest that reading speed performance can be at least partially accounted for by
      the extraction of essential structural information from visual stimuli,
      consisting of a domain-general and a domain-specific expertise-based portion.

PMID- 21903251
TI  - Relation between falciparum malaria and bacteraemia in Kenyan children: a
      population-based, case-control study and a longitudinal study.
AB  - BACKGROUND: Many investigators have suggested that malaria infection predisposes
      individuals to bacteraemia. We tested this hypothesis with mendelian
      randomisation studies of children with the malaria-protective phenotype of sickle
      cell trait (HbAS). METHODS: This study was done in a defined area around Kilifi
      District Hospital, Kilifi, Kenya. We did a matched case-control study to identify
      risk factors for invasive bacterial disease, in which cases were children aged 3
      months to 13 years who were admitted to hospital with bacteraemia between Sept
      16, 1999, and July 31, 2002. We aimed to match two controls, by age, sex,
      location, and time of recruitment, for every case. We then did a longitudinal
      case-control study to assess the relation between HbAS and invasive bacterial
      disease as malaria incidence decreased. Cases were children aged 0-13 years who
      were admitted to hospital with bacteraemia between Jan 1, 1999, and Dec 31, 2007.
      Controls were born in the study area between Jan 1, 2006, and June 23, 2009.
      Finally, we modelled the annual incidence of bacteraemia against the community
      prevalence of malaria during 9 years with Poisson regression. RESULTS: In the
      matched case-control study, we recruited 292 cases-we recruited two controls for
      236, and one for the remaining 56. Sickle-cell disease, HIV, leucocyte haemozoin
      pigment, and undernutrition were positively associated with bacteraemia and HbAS
      was strongly negatively associated with bacteraemia (odds ratio 0.36; 95% CI 0.20
      0.65). In the longitudinal case-control study, we assessed data from 1454 cases
      and 10,749 controls. During the study period, the incidence of admission to
      hospital with malaria per 1000 child-years decreased from 28.5 to 3.45, with a
      reduction in protection afforded by HbAS against bacteraemia occurring in
      parallel (p=0.0008). The incidence of hospital admissions for bacteraemia per
      1000 child-years also decreased from 2.59 to 1.45. The bacteraemia incidence rate
      ratio associated with malaria parasitaemia was 6.69 (95% CI 1.31-34.3) and, at a
      community parasite prevalence of 29% in 1999, 62% (8.2-91) of bacteraemia cases
      were attributable to malaria. INTERPRETATION: Malaria infection strongly
      predisposes individuals to bacteraemia and can account for more than half of all
      cases of bacteraemia in malaria-endemic areas. Interventions to control malaria
      will have a major additional benefit by reducing the burden of invasive bacterial
      disease. FUNDING: Wellcome Trust.

PMID- 21903252
TI  - Bahrain: continuing imprisonment of doctors.

PMID- 21903253
TI  - Lyme borreliosis.
AB  - Lyme borreliosis (Lyme disease) is caused by spirochaetes of the Borrelia
      burgdorferi sensu lato species complex, which are transmitted by ticks. The most
      common clinical manifestation is erythema migrans, which eventually resolves,
      even without antibiotic treatment. However, the infecting pathogen can spread to
      other tissues and organs, causing more severe manifestations that can involve a
      patient's skin, nervous system, joints, or heart. The incidence of this disease
      is increasing in many countries. Laboratory evidence of infection, mainly
      serology, is essential for diagnosis, except in the case of typical erythema
      migrans. Diagnosed cases are usually treated with antibiotics for 2-4 weeks and
      most patients make an uneventful recovery. No convincing evidence exists to
      support the use of antibiotics for longer than 4 weeks, or for the persistence of
      spirochaetes in adequately treated patients. Prevention is mainly accomplished by
      protecting against tick bites. There is no vaccine available for human beings.

PMID- 21903254
TI  - Malaria and bacteraemia in African children.

PMID- 21903255
TI  - MRI of transplanted surface-labeled pancreatic islets with heparinized
      superparamagnetic iron oxide nanoparticles.
AB  - Transplantation of insulin-secreting pancreatic islets can provide real-time
      regulation of blood glucose in patients with type 1 diabetes mellitus. Currently,
      noninvasive and repetitive monitoring of islet engraftment and function is an
      emerging and promising modality for successful islet transplantation. Here we
      report a new technique for highly sensitive in vivo magnetic resonance (MR)
      imaging of transplanted pancreatic islets. To this end, heparinized
      superparamagnetic iron oxide (heparin-SPIO) nanoparticle was newly synthesized
      for chemical conjugation onto islet surface. Compared to typical cellular
      labeling of Feridex((r)) via random endocytosis, chemical conjugation of heparin
      SPIO was stable and improved the hypointensity of transplanted islets due to
      surface modification of every islet. These heparin-SPIO-conjugated islets showed
      normal viability and insulin secretion, and were quantified by spin echo T(2)
      weighted MR imaging with linear correlation depending on transplanted islet mass
      in vitro and in vivo for 30 days. Also, from the immunohistochemistry, we
      confirmed the existence of heparin-SPIO and insulin biosynthesis in transplanted
      islets. However, Feridex-uptake islets showed late glucose responsiveness
      according to changing glucose concentration although they could normally control
      the blood glucose levels in diabetic mouse. Thus, we anticipate that this surface
      labeling with heparin-SPIO can be directly applicable for MR imaging of
      transplanted islets.

PMID- 21903256
TI  - The promotion of neurite sprouting and outgrowth of mouse hippocampal cells in
      culture by graphene substrates.
AB  - Graphene has been demonstrated in many biomedical applications and its potentials
      for neural interfacing. Emerging concerns on graphene, as a biomedical material,
      are its biocompatibility and how biologically targeted tissue/cells respond to
      it. Relatively few studies attempted to address the interactions of graphene or
      its derivatives with the tissues/cells, while very few reports on neural system.
      In this study, we tried to explore how neurites, one of the key structures for
      neural functions, are affected by graphene during the development until
      maturation in a mouse hippocampal culture model. The results reveal that graphene
      substrates exhibited excellent biocompatibility, as cell viability and morphology
      were not affected. Meanwhile, neurite numbers and average neurite length on
      graphene were significantly enhanced during 2-7 days after cell seeding compared
      with tissue culture polystyrene (TCPS) substrates. Especially on Day 2 of the
      neural development period, graphene substrates efficiently promoted neurite
      sprouting and outgrowth to the maximal extent. Additionally, expression of growth
      associate protein-43 (GAP-43) was examined in both graphene and TCPS groups.
      Western blot analysis showed that GAP-43 expression was greatly enhanced in
      graphene group compared to TCPS group, which might result in the boost of neurite
      sprouting and outgrowth. This study suggests the potential of graphene as a
      material for neural interfacing and provides insight into the future biomedical
      applications of graphene.

PMID- 21903259
TI  - Single nonfouling hydrogels with mechanical and chemical functionality gradients.
AB  - Hydrogels are widely studied as tissue engineering scaffolds, but the biological
      tissues they are designed to mimic are often complex tissues with non-uniform
      chemical and mechanical profiles. This work reports a new strategy to create
      hydrogels composed of a continuous sheet of a single nonfouling but
      functionalizable material with mechanical and/or chemical functionality
      gradients. By using different combinations of functionalizable or
      nonfunctionalizable versions of nonfouling carboxybetaine methacrylate (CBMA) and
      carboxybetaine dimethacrylate crosslinker (CBMAX), various hydrogels with
      gradients of crosslinking densities and/or functionalizable groups can be
      created. In this work, we demonstrate this concept with two nonfouling hydrogels,
      both with a mechanical gradient: one with uniform functionalizability and the
      other with a gradient in chemical functionalizability. With this versatile
      system, hydrogels with built-in gradient profiles of various types can be
      controlled at will for a given application.

PMID- 21903257
TI  - Biocompatibility and biofilm inhibition of N,N-hexyl,methyl-polyethylenimine
      bonded to Boston Keratoprosthesis materials.
AB  - The biocompatibility and antibacterial properties of N,N-hexyl,methyl
      polyethylenimine (HMPEI) covalently attached to the Boston Keratoprosthesis (B
      KPro) materials was evaluated. By means of confocal and electron microscopies, we
      observed that HMPEI-derivatized materials exert an inhibitory effect on biofilm
      formation by Staphylococcus aureus clinical isolates, as compared to the parent
      poly(methyl methacrylate) (PMMA) and titanium. There was no additional corneal
      epithelial cell cytotoxicity of HMPEI-coated PMMA compared to that of control
      PMMA in tissue cultures in vitro. Likewise, no toxicity or adverse reactivity was
      detected with HMPEI-derivatized PMMA or titanium compared to those of the control
      materials after intrastromal or anterior chamber implantation in rabbits in vivo.

PMID- 21903258
TI  - Synergistic effect of folate-mediated targeting and verapamil-mediated P-gp
      inhibition with paclitaxel -polymer micelles to overcome multi-drug resistance.
AB  - Multidrug resistance (MDR) in tumor cells is a significant obstacle for
      successful cancer chemotherapy. Overexpression of drug efflux transporters such
      as P-glycoprotein (P-gp) is a key factor contributing to the development of tumor
      drug resistance. Verapamil (VRP), a P-gp inhibitor, has been reported to be able
      to reverse completely the resistance caused by P-gp. For optimal synergy, the
      drug and inhibitor combination may need to be temporally colocalized in the tumor
      cells. Herein, we investigated the effectiveness of simultaneous and targeted
      delivery of anticancer drug, paclitaxel (PTX), along with VRP, using DOMC-FA
      micelles to overcome tumor drug resistance. The floate-functionalized dual agent
      loaded micelles resulted in the similar cytotoxicity to PTX-loaded micelles/free
      VRP combination and co-administration of two single-agent loaded micelles, which
      was higher than that of PTX-loaded micelles. Enhanced therapeutic efficacy of
      dual agent micelles could be ascribe to increased accumulation of PTX in drug
      resistant tumor cells. We suggest that the synergistic effect of folate receptor
      mediated internalization and VRP-mediated overcoming MDR could be beneficial in
      treatment of MDR solid tumors by targeting delivery of micellar PTX into tumor
      cells. As a result, the difunctional micelle systems is a very promising approach
      to overcome tumor drug resistance.

PMID- 21903260
TI  - The effect of hydrophilic chain length and iRGD on drug delivery from
      poly(epsilon-caprolactone)-poly(N-vinylpyrrolidone) nanoparticles.
AB  - Poly(epsilon-caprolactone)-b-Poly(N-vinylpyrrolidone) (PCL-b-PVP) copolymers with
      different PVP block length were synthesized by xanthate-mediated reverse addition
      fragment transfer polymerization (RAFT) and the xanthate chain transfer agent on
      chain end was readily translated to hydroxy or aldehyde for conjugating various
      functional moieties, such as fluorescent dye, biotin hydrazine and tumor homing
      peptide iRGD. Thus, PCL-PVP nanoparticles were prepared by these functionalized
      PCL-b-PVP copolymers. Furthermore, paclitaxel-loaded PCL-PVP nanoparticles with
      satisfactory drug loading content (15%) and encapsulation efficiency (>90%) were
      obtained and used in vitro and in vivo antitumor examination. It was demonstrated
      that the length of PVP block had a significant influence on cytotoxicity, anti
      BSA adsorption, circulation time, stealth behavior, biodistribution and antitumor
      activity for the nanoparticles. iRGD on PCL-PVP nanoparticle surface facilitated
      the nanoparticles to accumulate in tumor site and enhanced their penetration in
      tumor tissues, both of which improved the efficacy of paclitaxel-loaded
      nanoparticles in impeding tumor growth and prolonging the life time of H22 tumor
      bearing mice.

PMID- 21903261
TI  - The association of autophagy with polyethylenimine-induced cytotoxicity in
      nephritic and hepatic cell lines.
AB  - Polyethylenimine (PEI) is one of the most effective and widely used cationic
      macromolecules in experimental gene transfer/therapy protocols. However, the
      further clinical application of PEI is largely impeded by its cytotoxicity. Here
      we performed a fundamental investigation on the mechanism of PEI-induced
      cytotoxicity in both hepatic and nephritic cell lines. It was demonstrated that
      besides necrosis and apoptosis, autophagy was apparently associated with PEI
      induced cytotoxicity and contributed to aggravated cell damage. Specifically, at
      the early stage (3 h) of PEI-induced cytotoxicity, autophagy was mainly
      correlated with lysosome damage, but in the later phase (after a 24-h recovery),
      autophagy was mainly related with mitochondrial injury. Modulation of Rab5, Rab7
      expression and inhibition of clathrin-mediated endocytosis pathway significantly
      affected the formation of autophagosome, which suggested that the endolysosome
      transport pathway especially the clathrin-mediated endocytosis at least partly
      facilitated PEI-induced autophagy. As PEI-induced autophagy played a causative
      role in its cytotoxicity, it's highly recommended to design PEI-based gene
      carriers that could avoid the endolysosome transport pathway.

PMID- 21903263
TI  - Increased oxidative stress in the placenta tissue and cell culture of tumour
      bearing pregnant rats.
AB  - Placental dysfunction leads to foetal damage, which jeopardises the exchange
      between the maternal and foetal systems. We evaluated the effects of tumour
      growth on the activity of antioxidant enzymes and oxidative stress in placental
      tissue and cell culture from tumour-bearing pregnant rats compared to non-tumour
      bearing pregnant rats that were ascitic fluid injected. Ascitic fluid is obtained
      from Walker tumour-bearing rats and contains a cytokine called Walker factor
      (WF), which is a molecule similar to proteolysis-inducing factor (PIF), and
      induces changes in protein metabolism and oxidative stress. Pregnant Wistar rats
      were distributed into control (C), tumour-bearing (W) and ascitic fluid injected
      (A) groups and were sacrificed on days 16, 19 and 21 of pregnancy to analyse the
      profile of enzyme activities (glutathione-S-transferase (GST), catalase (CAT),
      alkaline phosphatase (AP)) and malondialdehyde (MDA) content in placental tissue.
      Meanwhile, placenta samples from all groups were obtained on day 21, placed in
      primary culture and treated with WF for 72 h. The presence of tumour or ascitic
      fluid reduced the protein content of the placental tissue. On day 16 there was a
      significant reduction in AP activity in W rats, and on day 19, CAT activity and
      MDA content significantly increased. These results indicate that the presence of
      cancer decreased antioxidant enzyme capacity in the placenta, increasing the
      amount of oxidation in these cells, which may contribute to irreversible
      placental damage and compromisefoetal development. WF treatment induces similar
      changes in placental cells in primary culture, resulting in less cell viability
      and increased oxidative stress. These results indicate that WF, provided by the
      tumour or inoculation of ascitic fluid, has negative effects on placental
      homeostasis, which impairs foetal health.

PMID- 21903264
TI  - Influence of sex and glucocorticoid exposure on preterm placental pro-oxidant
      antioxidant balance.
AB  - Glucocorticoids (GC) are known to influence fetal ROS production and anti-oxidant
      defences yet little attention has focused on the potential for effects in the
      placenta. We hypothesised that antenatal GC exposure alters placental pro-oxidant
      anti-oxidant balance sex-specifically, based upon the known relationship between
      male sex and poor pregnancy outcome. Placentae were collected from 60 women who
      delivered between 24 and 31 completed weeks gestation and placental oxidative and
      nitrative stress (protein carbonyl, lipid hydroperoxide, and nitrotyrosine
      concentration) and anti-oxidant enzyme activity (glutathione peroxidase,
      thioredoxin reductase, and superoxide dismutase) measured. A pro-oxidant state
      was observed in placentae of male compared to female infants born within 72 h of
      antenatal GC exposure, with higher levels of protein carbonyl content (p = 0.04),
      lipid hydroperoxide (p < 0.01) and nitrotyrosine content (p = 0.02), and lower
      levels of glutathione peroxidase activity (p = 0.01). A pro-oxidant state
      continued to be observed in placentae of males compared to females born outside
      of 72 h, with higher protein carbonyl content (p = 0.04) and lower glutathione
      peroxidase activity (p = 0.01) than females, however no differences in placental
      lipid hydroperoxide and nitrotyrosine content were observed. These sex-specific
      alterations in products of placental oxidative stress could not purely be
      explained by differences in clinical illness severity (CRIB2 score). Therefore,
      these sex-specific alterations in placental pro-oxidant-antioxidant balance in
      response to antenatal betamethasone exposure, independent of illness severity,
      could contribute to the patho-physiologic processes underlying oxygen radical
      diseases of the newborn, conditions known to exhibit a male excess.

PMID- 21903262
TI  - Hydrogel design for cartilage tissue engineering: a case study with hyaluronic
      acid.
AB  - Hyaline cartilage serves as a low-friction and wear-resistant articulating
      surface in load-bearing, diarthrodial joints. Unfortunately, as the avascular,
      alymphatic nature of cartilage significantly impedes the body's natural ability
      to regenerate, damage resulting from trauma and osteoarthritis necessitates
      repair attempts. Current clinical methods are generally limited in their ability
      to regenerate functional cartilage, and so research in recent years has focused
      on tissue engineering solutions in which the regeneration of cartilage is pursued
      through combinations of cells (e.g., chondrocytes or stem cells) paired with
      scaffolds (e.g., hydrogels, sponges, and meshes) in conjunction with stimulatory
      growth factors and bioreactors. A variety of synthetic and natural materials have
      been employed, most commonly in the form of hydrogels, and these systems have
      been tuned for optimal nutrient diffusion, connectivity of deposited matrix,
      degradation, soluble factor delivery, and mechanical loading for enhanced matrix
      production and organization. Even with these promising advances, the complex
      mechanical properties and biochemical composition of native cartilage have not
      been achieved, and engineering cartilage tissue still remains a significant
      challenge. Using hyaluronic acid hydrogels as an example, this review will follow
      the progress of material design specific to cartilage tissue engineering and
      propose possible future directions for the field.

PMID- 21903265
TI  - Promotional etiology for common childhood acute lymphoblastic leukemia: the
      infective lymphoid recovery hypothesis.
AB  - This paper speculates on the role of infection in modifying a young child's risk
      of promoting precursor B-cell acute lymphoblastic leukemia (ALL). It is suggested
      that the heat shock instigated by infections, particularly in infancy, stimulates
      Th1 pro-inflammatory cytokines and an apoptosis-inhibitory environment. This
      infective stress also increases the number of cooperating oncogenic mutations in
      pre-leukemic cells, especially if the primary adaptive immune response is
      delayed. The glucocorticoid release that follows leads to acute thymic
      involution, a decline in antitumor immunity, and maturation arrest of B
      lymphocytes. The infective lymphoid recovery hypothesis addresses an apparent
      contradiction-that a non-hygienic environment primes the adaptive immune response
      and is protective against childhood ALL, while multiple infections occurring
      later increase the risk of childhood ALL. In affluent (compared to less-affluent)
      societies, the characteristic ALL incidence peak in early childhood, and the
      shortened time to diagnosis, arise from surviving recurrent infections and the
      accumulated loss and recovery of lymphoid tissue. Evidence supporting the
      hypothesis, such as the role of lymphoid tissue reconstitution cytokines that
      stimulate proliferation stress on B-cell progenitors, comes from the study of
      children with congenital syndromes that are susceptible to leukemia.

PMID- 21903266
TI  - Maternal experiences of childhood abuse and intimate partner violence:
      Psychopathology and functional impairment in clinical children and adolescents.
AB  - OBJECTIVES: The current study examined the independent effects of mothers'
      childhood abuse (CA) and intimate partner violence (IPV) on psychopathology and
      functional impairment in children; and the potential moderating and mediating
      role of individual and family factors in these relationships. Additionally, this
      study explored the potential cumulative effects of both maternal CA and IPV on
      children's outcomes. METHOD: The sample included 547 Spanish children and
      adolescents aged between 8 and 17 years, and their parents, who had accessed
      mental health services. The assessment was based on structured interviews with
      the children and their parents. Statistical analyses were carried out through
      hierarchical multiple, negative-binomial and logistic regressions, and Structural
      Equation Models. RESULTS: Children whose mothers experienced CA and those whose
      mothers suffered physical IPV showed increased DSM-IV disruptive disorders and
      externalizing behavior problems, respectively. Children who directly observed
      physical IPV and also suffered physical punishment by parents showed increased
      internalizing problems. IPV had effects, either direct or indirect by physical
      punishment, on children's externalizing problems. Cumulative effect analyses
      indicated that the prevalence of disruptive disorders was highest in children
      whose mothers had suffered both CA and IPV. CONCLUSION: Spanish children whose
      mothers have suffered CA, IPV or both, are at high risk of serious conduct
      problems, whereas children exposed to IPV and who were also physically abused are
      at greater risk of internalizing problems. Physical punishment of children
      contributes in part to explain externalizing problems of IPV-exposed children.
      These findings indicate potential targets of assessment and intervention for
      families seeking help in mental health services.

PMID- 21903267
TI  - Concentrations and sources of PAHs in surface sediments of the Fenhe reservoir
      and watershed, China.
AB  - Sixteen PAHs in surface sediments at 28 sites throughout Fenhe reservoir and
      watershed were measured. The ?PAHs concentrations ranged from 539.0 to 6281.7
      with the mean of 2214.8ng/g. The 2-3 rings PAHs, contributing 55 percent to
      ?PAHs, were the dominant species. Twenty-eight sites were grouped into three
      segments: Fenhe principal stream, estuaries of main branch streams, and Fenhe
      reservoir. ?PAHs was highest in the estuaries of main branch streams. The
      ecological risk assessment was studied by biological thresholds. The results
      showed levels of PAHs might cause mild but not acute adverse biological effects.
      In addition, PAHs ratios, PCA/MLR and hierarchical clustering analysis were
      applied to evaluate the possible sources. Coal combustion (35 percent), diesel
      and gasoline emissions (29 percent and 16 percent, respectively) might be the
      important sources. For sites in Fenhe reservoir, the major sources were complex,
      while other two segments were mainly influenced by coal combustion source.

PMID- 21903268
TI  - Detection and characterization of methicillin-resistant Staphylococcus
      pseudintermedius in healthy dogs in La Rioja, Spain.
AB  - The objective was to identify the methicillin-resistant coagulase-positive
      staphylococci (MRCoPS) nasal carriage rate of healthy dogs in La Rioja (Spain)
      and to characterize the recovered isolates by different molecular techniques.
      Nasal samples from 196 dogs were obtained (98 household-dogs, 98 pound-dogs).
      Isolates were identified and characterized by spa-, SCCmec- and MLST-typing, SmaI
      PFGE, antimicrobial susceptibility, determination of antimicrobial resistance and
      toxin genes profiling. S. pseudintermedius was the only species recovered. Nine
      methicillin-resistant S. pseudintermedius (MRSP) were obtained from 9 of 196
      sampled dogs (8% pound-dogs, 1% household-dogs). MRSP isolates were typed
      (MLST/PFGE/spa/SCCmec) as: ST71/A/t02/II-III (7 isolates), ST92/C/t06/V (1
      isolate), and ST26/B/non-typable/non-typable (1 isolate). All MRSP were resistant
      to [resistance gene/number isolates]: beta-lactams [mecA+blaZ/9], tetracycline
      [tet(K)/7, tet(M)/2], macrolides and lincosamides [erm(B)/9], aminoglycosides
      [aacA-aphD+aadE+aphA-3/9], and co-trimoxazol [dfr(G)/9]. Eight MRSP isolates
      showed also resistance to fluoroquinolones and amino acid changes in GyrA
      [Ser84Leu+Glu714Lys, 7 isolates; Ser84Leu, 1 isolate] and GrlA [Ser80Ile, 8
      isolates] proteins were detected. The remaining isolate was chloramphenicol
      resistant and harboured cat(pC221) gene. All MRSP isolates harboured the aadE
      sat4-aphA-3 multiresistance-gene-cluster linked to erm(B) gene as well as the
      siet, si-ent and lukS/F-I toxin genes. MRSP is a moderately common (4.6%)
      colonizer of healthy dogs in Spain. A major MRSP lineage (ST71) was detected and
      its future evolution should be tracked.

PMID- 21903269
TI  - The impact of Trichinella spiralis excretory-secretory products on dendritic
      cells.
AB  - Parasitic nematode Trichinella spiralis exert immunomodulatory effect on the host
      immune response through excretory-secretory products (ES L1) released from the
      encysted muscle larvae. Rat bone-marrow derived dendritic cells (DCs) stimulated
      with ES L1 antigens acquire semi-matured status and induce Th2 and regulatory
      responses in vitro and in vivo. Priming naive T cells in vitro with ES L1 pulsed
      DCs caused strong Th2 polarization, accompanied by elevated production of
      regulatory cytokines IL-10 and TGF-beta and no increase in the proportion of
      CD4+CD25+Foxp3+ among the effector T cell population. In vivo T cell priming
      resulted in mixed Th1/Th2 cytokine response, with the dominance of the Th2 type
      and elevated levels of regulatory cytokines. Significant increase in the
      proportion of CD4+CD25+Foxp3+ cells was found among recipient's spleen cells. We
      have achieved to create immune status characteristic for the live infection by in
      vivo application of DCs educated with ES L1 antigens.

PMID- 21903270
TI  - Monoclonal antibodies against the leptospiral immunoglobulin-like proteins A and
      B conserved regions.
AB  - Leptospirosis is an infectious disease caused by pathogenic spirochetes of the
      genus Leptospira that affects humans and a wide variety of animals. Recently the
      genomes of Leptospira interrogans, Leptospira borgpetersenii and Leptospira
      biflexa species were sequenced allowing the identification of new virulence
      factors involved in survival and pathogenesis of bacteria. LigA and LigB are
      surface-exposed bacterial adhesins whose expression is correlated with the
      virulence of Leptospira strains. In this study, we produced and characterized
      five monoclonal antibodies (MAbs) against a recombinant fragment of LigB
      (rLigBrep) with approximately 54kDa that comprise the portions of LigA and LigB
      (domains 2-7). The 5 MAbs obtained were of the IgG1 (2) and IgG2b (3) isotypes
      and their affinity constants for rLigBrep ranged from 7*10(7) M(-1) to 4*10(8) M(
      1). The MAbs were able to react with the native antigen on the L. interrogans, L.
      borgpetersenii and Leptospira noguchii surfaces by indirect immunofluorescence,
      immunoblotting and immunoelectron microscopy. These results demonstrate that the
      MAbs anti-rLigBrep can be useful to complement genetic studies and to aid studies
      aiming understanding the role of Lig proteins in Leptospira pathogenesis and the
      development of Lig-based vaccines and improved diagnostic tests for
      leptospirosis.

PMID- 21903271
TI  - Diagnosis of antisocial personality disorder and criminal responsibility.
AB  - The present study empirically investigates whether personality disorders and
      psychopathic traits in criminal suspects are reasons for diminished criminal
      responsibility or enforced treatment in high security hospitals. Recently, the
      tenability of the claim that individuals with personality disorders and
      psychopathy can be held fully responsible for crimes has been questioned on
      theoretical bases. According to some interpretations, these disorders are due to
      cognitive, biological and developmental deficits that diminish the individual's
      accountability. The current article presents two studies among suspects of
      serious crimes under forensic evaluation in a Dutch forensic psychiatric
      observation clinic. The first study examined how experts weigh personality
      disorders in their conclusions as far as the degree of criminal responsibility
      and the need for enforced forensic psychiatric treatment are concerned (n=843).
      The second study investigated associations between PCL-R scores and experts'
      responsibility and treatment advisements (n=108). The results suggest that in
      Dutch forensic practice, the presence of a personality disorder decreased
      responsibility and led to an advice for enforced forensic treatment. Experts also
      take characteristics of psychopathy concerning impulsivity and (ir)responsibility
      into consideration when judging criminal accountability. Furthermore, they deem
      affective deficiencies sufficiently important to indicate suspects' threat to
      society or dangerousness and warrant a need for forensic treatment.

PMID- 21903272
TI  - PTSD symptom clusters, feelings of revenge, and perceptions of perpetrator
      punishment severity in victims of interpersonal violence.
AB  - Feelings of revenge have often been found to correlate with symptoms of
      posttraumatic stress disorder (PTSD). Which PTSD symptom cluster prevails in this
      association is, however, unknown. Furthermore, previous studies suggest that
      revenge may be satisfied by perceptions of perpetrator punishment severity, but
      did not control for concurrent symptoms of PTSD. Therefore, this study explored
      associations between PTSD symptom clusters, feelings of revenge, and perceived
      perpetrator punishment severity in a sample of victims of interpersonal violence.
      Results indicated that the re-experiencing/intrusion symptom cluster was the only
      index of PTSD which was related to victims' feelings of revenge (n=207). Revenge
      correlated negatively with perceptions of punishment severity in victim who knew
      that the perpetrator had been sentenced, but not after adjustment for PTSD
      symptoms (n=96).

PMID- 21903273
TI  - Vibrio vulnificus IlpA induces MAPK-mediated cytokine production via TLR1/2
      activation in THP-1 cells, a human monocytic cell line.
AB  - Vibrio vulnificus is a pathogenic bacterium causing primary septicemia, which is
      followed by a classical septic shock pathway including an overwhelming
      inflammatory cytokine response. V. vulnificus IlpA is a potent immunogenic
      lipoprotein that triggers cytokine production in human monocytes by activating
      the toll-like receptor 2 (TLR2). In this study, we further defined the IlpA
      signaling pathways involved in cytokine production in the human monocytic cell
      line, THP-1. TLR2 was involved in cytokine production by complexing with TLR1,
      but not with TLR6. MyD88 was necessary for IlpA-induced cytokine expression
      through TLR1/TLR2. Three mitogen activated protein kinases (MAPK), p38, ERK1/2,
      and JNK, were activated in THP-1 cells stimulated with recombinant IlpA (rIlpA).
      Selective inhibition of each MAPK resulted in significant decrease of rIlpA
      induced cytokine production. Especially, functional TLR2 was necessary for IlpA
      induced activation of p38 and JNK. IlpA augmented the DNA-binding activity of
      nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) transcriptional
      factors to their recognition sites in THP-1 cells. These results suggest that
      serial activation of TLR1/TLR2, MyD88, the three MAPKs, and NF-kappaB/AP-1
      comprises the signaling pathway responsible for proinflammatory cytokine
      production by V. vulnificus IlpA.

PMID- 21903274
TI  - Crystal structure of the major peanut allergen Ara h 1.
AB  - Ara h 1, a 7S globulin, is one of the three major peanut allergens. We previously
      reported the crystallization of the core region of recombinant Ara h 1. Here, we
      present the crystal structure of the Ara h 1 core at a resolution of 2.43 A. We
      also assayed the Ara h 1 core thermal stability and compared its final structure
      against other 7S globulins. The Ara h 1 core has a thermal denaturation
      temperature of 88.3 degrees C and a structure that is very similar to other 7S
      globulins. Previously identified linear IgE epitopes were also mapped on the
      three-dimensional structure. Most linear epitopes were found in the extended loop
      domains and the coils between the N- and C-terminal modules, while others were
      found in the less accessible beta-sheets of the C-terminal core beta-barrel
      domain of each monomer. Most of these epitopes become either slightly or
      significantly buried upon trimer formation, implying that allergen digestion in
      the gut is required for these epitopes to be accessible to immunoglobulins. Our
      findings also suggest that both intact and partially degraded allergens should be
      employed in future diagnostic and immunotherapeutic strategies.

PMID- 21903275
TI  - Object perception in 5-month-old infants of clinically depressed and nondepressed
      mothers.
AB  - Five-month-old infants of clinically depressed and nondepressed mothers were
      familiarized to a wholly novel object and afterward tested for their
      discrimination of the same object presented in the familiar and in a novel
      perspective. Infants in both groups were adequately familiarized, but infants of
      clinically depressed mothers failed to discriminate between novel and familiar
      views of the object, whereas infants of nondepressed mothers successfully
      discriminated. The difference in discrimination between infants of depressed and
      nondepressed mothers is discussed in light of infants' differential object
      processing and maternal sociodemographics, mind-mindedness, depression, stress,
      and interaction styles that may moderate opportunities for infants to learn about
      their world or influence the development of their perceptuocognitive capacities.

PMID- 21903276
TI  - Links between mothers' coping styles, toddler reactivity, and sensitivity to
      toddler's negative emotions.
AB  - The extent to which engaged maternal coping styles moderate the association
      between toddler's temperamental reactivity and mothers' sensitivity to children's
      negative emotions was examined in 89 mother-child dyads. Primiparous mothers
      completed a measure of coping styles prenatally. When toddlers were 16 months
      old, mothers completed a measure of perceived toddler temperament and a self
      report of how they respond to toddler negative emotions, and maternal sensitivity
      and temperamental reactivity were observed during emotionally arousing tasks in
      the laboratory. Mothers' disengaged coping style was positively associated with
      self-reported insensitive responses to children's negative emotions. Engaged
      coping moderated the association between toddler temperamental reactivity and
      both self-reported insensitive responses and observed maternal sensitivity, such
      that temperamental reactivity was more strongly linked with less sensitive
      maternal behavior when engaged coping was low.

PMID- 21903277
TI  - Social anxiety in the general population: introducing abbreviated versions of
      SIAS and SPS.
AB  - BACKGROUND: Social anxiety is characterized by the experience of stress,
      discomfort and fear in social situations, and is associated with substantial
      personal and societal burden. Two questionnaires exist that assess the aspects of
      social anxiety, i.e. social interaction anxiety (SIAS) and social phobia (SPS).
      There is no agreement in literature on the dimensionality of social anxiety.
      Further, the length of a questionnaire may negatively affect response rates and
      participation at follow-up occasions. AIM: To explore the structure of social
      anxiety in the general population, and to examine psychosocial and
      sociodemographic correlates. Our second aim was to construct abbreviated versions
      of SIAS and SPS that can be easily used and with minimal burden. METHOD: A total
      of 1598 adults from the general Dutch population completed a survey asking
      information on social anxiety, mood and demographics. Exploratory and
      confirmatory factor analyses as well as reliability analysis with item-total
      statistics were performed. RESULTS: Confirmatory factor analysis revealed a 3
      factor structure for social phobia, and a 2-factor structure for the SIAS, with
      the second factor containing both reversely scored items. The abbreviated
      versions of SPS (11 items) and SIAS (10 items) show excellent discriminant and
      construct validity (Cronbach's alpha=.90 and .92), while specificity analysis
      showed that gender, marital status and educational level (SIAS(10): p<.0005;
      SPS(11): p<.0005) are important determinants of social anxiety. CONCLUSION: In
      the general population, social interaction anxiety and social phobia are two
      aspects of a higher-order factor of social anxiety. Social anxiety is validly
      captured by the short versions of SPS and SIAS, reducing the questionnaire burden
      for participants in epidemiological and biobehavioral research.

PMID- 21903278
TI  - Genetic structure of personality factors and bipolar disorder in families
      segregating bipolar disorder.
AB  - BACKGROUND: Bipolar disorder (BPD) has been associated with variations in
      personality dimensions, but the nature of this relationship has been unclear. In
      this study, the heritabilities of BPD and the Big Five personality factors and
      the genetic correlations between BPD and personality factors are reported.
      METHODS: The participants in this study were 1073 individuals from 172 families
      of Mexican or Central American ancestry. Heritabilities and genetic correlations
      were calculated under a polygenic model using the maximum-likelihood method of
      obtaining variance components implemented in the SOLAR software package. RESULTS:
      Heritabilities of 0.49, 0.43, and 0.43 were found for the narrowest phenotype
      (schizoaffective bipolar and bipolar I), the intermediate phenotype
      (schizoaffective bipolar, bipolar I, and bipolar II), and the broadest phenotype
      (schizoaffective bipolar, bipolar I, bipolar II, and recurrent depression),
      respectively. For the Big Five personality factors, heritabilities were 0.25 for
      agreeableness, 0.24 for conscientiousness, 0.24 for extraversion, 0.23 for
      neuroticism, and 0.32 for openness to experience. For the narrowest phenotype, a
      significant negative correlation (-0.32) with extraversion was found. For the
      broadest phenotype, negative correlations were found for agreeableness (-0.35),
      conscientiousness (-0.39), and extraversion (-0.44). A positive correlation
      (0.37) was found with neuroticism. LIMITATIONS: It is not possible to determine
      whether aspects of personality are factors in the development of bipolar disorder
      or vice versa. The short form of the NEO does not provide the ability to examine
      in detail which facets of extraversion are most closely related to bipolar
      disorder or to compare our results with studies that have used the long version
      of the scale. CONCLUSIONS: This study establishes a partial genetic basis for the
      Big Five personality factors in this set of families, while the environmental
      variances demonstrate that non-genetic factors are also important in their
      influence on bipolar and personality phenotypes. BPD may be most associated with
      decreased extraversion (less interaction with one's surroundings) because
      patients spend more time in depressive than manic states.

PMID- 21903279
TI  - GPCR agonist binding revealed by modeling and crystallography.
AB  - Despite recent progress in structural coverage of the G-protein-coupled receptor
      (GPCR) family, high plasticity of these membrane proteins poses additional
      challenges for crystallographic studies of their complexes with different classes
      of ligands, especially agonists. The ability to predict computationally the
      binding of natural and clinically relevant agonists and corresponding changes in
      the receptor pocket, starting from inactive GPCR structures, is therefore of
      great interest for understanding GPCR biology and drug action. Comparison of
      computational models published in 2009 and 2010 with recently determined agonist
      bound structures of beta-adrenergic and adenosine A(2A) receptors reveals high
      accuracy of the predicted agonist binding poses (0.8 A and 1.7 A respectively)
      and receptor interactions. In the case of the beta(2)AR, energy-based models with
      limited backbone flexibility have also allowed characterization of side-chain
      rotations and a finite backbone shift in the pocket region as determinants of
      full, partial or inverse agonism. Development of accurate models of agonist
      binding for other GPCRs will be instrumental for functional and pharmacological
      studies, complementing biochemical and crystallographic techniques.

PMID- 21903280
TI  - TGFbeta1 contributes to cardiomyogenic-like differentiation of human bone marrow
      mesenchymal stem cells.
AB  - BACKGROUND: The majority of the protocols for cardiomyocyte differentiation of
      MSC use 5-azacytidine as an inducer. As transforming growth factor beta1 and 5
      azacytidine share similar target signaling pathways, we examined whether
      transforming growth factor beta1 can play a role in cardiac differentiation
      process in human mesenchymal stem cell of bone marrow origin. METHODS: The
      differentiation protocol involving transforming growth factor beta1 was compared
      with that of 5-azacytidine in these cells. The two differentiation regimes were
      compared using reverse transcriptase PCR, flow cytometry, and quantitative PCR.
      RESULTS: We observed that in both cases, acquired morphological features were
      similar. Protein and gene expression assays also indicated similar cardiac marker
      expression profile in both the differentiation conditions. Furthermore,
      transforming growth factor beta1 and 5-azacytidine allowed the acquisition of
      comparable levels of cardiac cell like molecular characteristic as attested by
      evaluation of myosin light chain-2v expression. CONCLUSION: In conclusion, we
      demonstrate that transforming growth factor beta1 can play a similar role in
      cardiac differentiation process of human bone marrow mesenchymal stem cells.

PMID- 21903281
TI  - Comparison of edge vascular response after sirolimus- and paclitaxel-eluting
      stent implantation.
AB  - BACKGROUND: To compare the edges vascular response, we analyzed the intravascular
      ultrasound (IVUS) parameters after implantation of the sirolimus-eluting stent
      (SES) or the paclitaxel-eluting stent (PES). METHODS: Two hundred-two angina
      patients (123 men; 61.5 +/- 9.2 years of age, SES: n = 91, PES: n=111) were
      enrolled. Both edge segments of the stent were analyzed. The change (Delta) of
      each parameter at follow-up was calculated. RESULTS: The edge restenosis rate was
      higher in the PES group. However, the Delta Vessel, Delta Plaque and Delta Lumen
      volume at 5mm edge segments were not different between the two groups except the
      Delta Plaque volume at the distal segment, higher in the PES than the SES group
      (6.6 +/- 15.7 vs. 1.0 +/- 13.1mm(3), P=.016). In the PES group, lumen area at the
      both 1mm edge segments decreased because of plaque progression (proximal, 1.9 +/-
      1.5 to 2.2 +/- 2.0mm(2), P=.095; distal, 0.6 +/- 1.1 to 1.0 +/- 1.4mm(2), P=.018)
      with negative remodeling (proximal, 9.9 +/- 2.4 to 9.4 +/- 2.6mm(2), P=.004;
      distal, 7.6 +/- 2.4 to 7.2 +/- 2.4mm(2), P=.052). Conversely, lumen area at these
      segments increased due to plaque regression (proximal, 3.2 +/- 1.8 to 2.1 +/-
      1.6mm(2), P=.000; distal, 1.5 +/- 1.4 to 0.9 +/- 1.3mm(2), P=.000) even though
      there was negative remodeling in the SES group (proximal, 10.1 +/- 2.4 to 9.6 +/-
      2.3mm(2), P=.019; distal, 7.8 +/- 2.3 to 7.5 +/- 2.3mm(2), P=.074). The Delta
      Plaque and Delta Lumen area at the both 1mm edge segments were more prominent in
      the PES group. CONCLUSIONS: Compared to SES, PES was associated with luminal
      reduction accompanied by plaque progression with negative remodeling at edge
      segments.

PMID- 21903282
TI  - The receptor tyrosine kinase inhibitor amuvatinib (MP470) sensitizes tumor cells
      to radio- and chemo-therapies in part by inhibiting homologous recombination.
AB  - BACKGROUND AND PURPOSE: RAD51 is a key protein involved in homologous
      recombination (HR) and a potential target for radiation- and chemotherapies.
      Amuvatinib (formerly known as MP470) is a novel receptor tyrosine kinase
      inhibitor that targets c-KIT and PDGFRalpha and can sensitize tumor cells to
      ionizing radiation (IR). Here, we studied amuvatinib mechanism on RAD51 and
      functional HR. MATERIALS AND METHODS: Protein and RNA analyses, direct repeat
      green fluorescent protein (DR-GFP) assay and polysomal fractioning were used to
      measure HR efficiency and global translation in amuvatinib-treated H1299 lung
      carcinoma cells. Synergy of amuvatinib with IR or mitomycin c (MMC) was assessed
      by clonogenic survival assay. RESULTS: Amuvaninib inhibited RAD51 protein
      expression and HR. This was associated with reduced ribosomal protein S6
      phosphorylation and inhibition of global translation. Amuvatinib sensitized cells
      to IR and MMC, agents that are selectively toxic to HR-deficient cells.
      CONCLUSIONS: Amuvatinib is a promising agent that may be used to decrease tumor
      cell resistance. Our work suggests that this is associated with decreased RAD51
      expression and function and supports the further study of amuvatinib in
      combination with chemotherapy and radiotherapy.

PMID- 21903283
TI  - Can diet combined with treatment scheduling achieve consistency of rectal filling
      in patients receiving radiotherapy to the prostate?
AB  - BACKGROUND AND PURPOSE: This pilot study investigates whether an individualized
      fluid and fibre prescription combined with a constant treatment can improve
      rectal filling consistency during radiotherapy. METHODS AND MATERIALS: Fibre,
      fluid intake and bowel function were assessed in 22 patients at a standard
      planning scan (SCT) and individualized dietary advice was prescribed to
      regularize bowel habit. Patients were requested to record frequency and type of
      bowel movements, fibre and fluid intake daily. Two subsequent CT scans were
      acquired at 7 (CCT1) and 10 days (CCT2) after SCT at a similar time. Rectal
      volume and gas were measured planning CT's and 'on treatment' cone beam CT scans.
      We hypothesised that the difference in volume between CCT1 and CCT2 would be less
      than the difference between SCT and CCT1. RESULTS: The mean (SD) change in volume
      between SCT to CCT1 and CCT1 to CCT2 was 5.68 cm(3) (26.2) and -8.6 cm(3) (40.1),
      respectively (p=0.292). Of the 22 patients scanned 20 provided a complete record
      of dietary intake and bowel motion. The majority of patients either achieved or
      exceeded prescription. Change in rectal gas was the only correlation with change
      in rectal volume. CONCLUSION: Patient self reporting of bowel motion, fibre,
      fluid intake was achievable but consistency of rectal filling was not improved.
      Improved understanding of the aetiology and management of rectal gas is
      indicated.

PMID- 21903284
TI  - Statistical control of the spectral quality index in electron beams.
AB  - BACKGROUND AND PURPOSE: In radiotherapy with electron linear accelerators, it is
      mandatory to guarantee the stability of beam output spectra. In this work we
      study the quality control of the magnitude that provides the beam spectral
      quality, by following statistical techniques usual in industry process. METHODS:
      We establish the differences between the measurement of the reference quality
      index, R(50,ion), which involves usually a costly procedure, and that of the
      index used for the statistical control, which can be done in an easier way and
      with a higher frequency. The methodology developed is applied to a Siemens
      Mevatron KDS electron linear accelerator, specifically for the 6, 12 and 18 MeV
      modes. The uncertainties of both procedures are evaluated and are correlated. A
      retrospective analysis of the data registered during more than 13 years is
      carried out using CUSUM algorithmic and moving range charts. RESULTS: The larger
      uncertainties in R(50,ion) come from the measurement device and the observer. The
      uncertainty in the measurement of the statistical control variable, which is
      mainly due to the geometry setup, is negligible against its intrinsic
      variability. The application of CUSUM charts pointed out different out of control
      situations linked in much cases to assignable causes. In addition, moving range
      charts showed up situations of anomalous functioning of the LINAC. CONCLUSIONS:
      Algorithmic CUSUM charts permit a nice monitoring of R(50,ion). If the
      variability is not controlled, by using charts such as the moving range ones, the
      number of false alarms could increase without a change in the mean value of
      R(50,ion).

PMID- 21903285
TI  - Preoperative concomitant boost intensity-modulated radiotherapy with oral
      capecitabine in locally advanced mid-low rectal cancer: a phase II trial.
AB  - PURPOSE: We aimed to assess the safety and efficacy of preoperative intensity
      modulated radiotherapy (IMRT) with oral capecitabine in patients with locally
      advanced mid-low rectal cancer using a concomitant boost technique. MATERIALS AND
      METHODS: Patients with resectable locally advanced mid-low rectal cancer (node
      negative >=T3 or any node-positive tumor) were eligible. The eligible patients
      received IMRT to 2 dose levels simultaneously (50.6 and 41.8 Gy in 22 fractions)
      with concurrent capecitabine 825 mg/m(2) twice daily 5 days/week. The primary end
      point included toxicity, postoperative complication, and pathological complete
      response rate (ypCR). The secondary endpoints included local recurrence rate,
      progression-free survival (PFS), and overall survival (OS). RESULTS: Sixty-three
      eligible patients were enrolled; five patients did not undergo surgery. Of the 58
      patients evaluable for pathologic response, the ypCR rate was 31.0% (95% CI 19.1
      42.9). Grade 3 toxicities included diarrhea (9.5%), radiation dermatitis (3.2%),
      and neutropenia (1.6%). There was no Grade 4 toxicity reported. Four (6.9%)
      patients developed postoperative complications. Two-year local recurrence rate,
      PFS, and OS were 5.7%, 90.5%, and 96.0%, respectively. CONCLUSIONS: The design of
      preoperative concurrent boost IMRT with oral capecitabine could achieve high rate
      of ypCR with an acceptable toxicity profile.

PMID- 21903286
TI  - Radiation dose response of normal lung assessed by Cone Beam CT - a potential
      tool for biologically adaptive radiation therapy.
AB  - BACKGROUND: Density changes of healthy lung tissue during radiotherapy as
      observed by Cone Beam CT (CBCT) might be an early indicator of patient specific
      lung toxicity. This study investigates the time course of CBCT density changes
      and tests for a possible correlation with locally delivered dose. METHODS: A
      total of 665 CBCTs in 65 lung cancer patients treated with IMRT/VMAT to 60 or 66
      Gy in 2 Gy fractions were analyzed. For each patient, CBCT lung density changes
      during the treatment course were related to the locally delivered dose. RESULTS:
      A dose response is observed for the patient population at the end of the
      treatment course. However, the observed dose response is highly variable among
      patients. Density changes at 10th and 20th fraction are clearly correlated to
      those observed at the end of the treatment course. CONCLUSIONS: CBCT density
      changes in healthy lung tissue during radiotherapy correlate with the locally
      delivered dose and can be detected relatively early during the treatment. If
      these density changes are correlated to subsequent clinical toxicity this assay
      could form the basis for biological adaptive radiotherapy.

PMID- 21903287
TI  - Target volume delineation variation in radiotherapy for early stage rectal cancer
      in the Netherlands.
AB  - PURPOSE: The aim of this study was to measure and improve the quality of target
      volume delineation by means of national consensus on target volume definition in
      early-stage rectal cancer. METHODS AND MATERIALS: The CTV's for eight patients
      were delineated by 11 radiation oncologists in 10 institutes according to local
      guidelines (phase 1). After observer variation analysis a workshop was organized
      to establish delineation guidelines and a digital atlas, with which the same
      observers re-delineated the dataset (phase 2). Variation in volume, most caudal
      and cranial slice and local surface distance variation were analyzed. RESULTS:
      The average delineated CTV volume decreased from 620 to 460 cc (p<0.001) in phase
      2. Variation in the caudal CTV border was reduced significantly from 1.8 to 1.2
      cm SD (p=0.01), while it remained 0.7 cm SD for the cranial border. The local
      surface distance variation (cm SD) reduced from 1.02 to 0.74 for anterior, 0.63
      to 0.54 for lateral, 0.33 to 0.25 for posterior and 1.22 to 0.46 for the
      sphincter region, respectively. CONCLUSIONS: The large variation in target volume
      delineation could significantly be reduced by use of consensus guidelines and a
      digital delineation atlas. Despite the significant reduction there is still a
      need for further improvement.

PMID- 21903288
TI  - Mycotoxin production by isolates of Fusarium lactis from greenhouse sweet pepper
      (Capsicum annuum).
AB  - Internal fruit rot, caused by Fusarium lactis, is an important disease of sweet
      pepper (Capsicum annuum) in Canadian greenhouses. Production of the mycotoxins
      fumonisin B1 (FB1), moniliformin (MON) and beauvericin (BEA) by F. lactis (17
      isolates) and the related species F. proliferatum (three isolates) and F.
      verticillioides (one isolate), which are also associated with internal fruit rot,
      was evaluated on rice medium. All 21 isolates examined were found to produce BEA,
      at concentrations ranging from 13.28 to 1674.60 ppm, while 13 of 17 F. lactis
      isolates and two of three F. proliferatum isolates produced MON (0.23 to 181.85
      ppm). Only one isolate of F. lactis produced detectable levels of FB1 in culture,
      whereas all three F. proliferatum isolates and the F. verticilloides isolate
      produced this mycotoxin (0.28 to 314 ppm). Production of FB1, MON and BEA was
      also evaluated in inoculated pepper fruits showing mild or severe symptoms of
      infection. FB1 could be detected in both lightly and heavily diseased fruit
      tissue after inoculation with F. lactis, F. proliferatum or F. verticilloides, at
      concentrations ranging from 0.61 to 8.04 ppm. BEA was also detected in lightly
      and heavily diseased fruit tissue inoculated with F. lactis, as well as in
      heavily diseased tissue inoculated with F. proliferatum (3.00 to 19.43 ppm), but
      not in tissue inoculated with F. verticilloides. MON was detected in all tissues
      inoculated with F. proliferatum or F. verticilloides, and in heavily diseased
      tissue inoculated with F. lactis (0.03 to 0.27 ppm). The three mycotoxins were
      also found in naturally infected sweet pepper fruits exhibiting symptoms of
      internal fruit rot and collected from a commercial greenhouse. The production of
      MON, BEA and FB1 alone or in combination by isolates of F. lactis suggests that
      development of internal fruit rot of sweet pepper is an important food safety
      concern, and that every effort should be made to cull infected fruit before it
      makes it to market.

PMID- 21903289
TI  - Diversity of acetic acid bacteria present in healthy grapes from the Canary
      Islands.
AB  - The identification of acetic acid bacteria (AAB) from sound grapes from the
      Canary Islands is reported in the present study. No direct recovery of bacteria
      was possible in the most commonly used medium, so microvinifications were
      performed on grapes from Tenerife, La Palma and Lanzarote islands. Up to 396 AAB
      were isolated from those microvinifications and identified by 16S rRNA gene
      sequencing and phylogenetic analysis. With this method, Acetobacter pasteurianus,
      Acetobacter tropicalis, Gluconobacter japonicus and Gluconacetobacter
      saccharivorans were identified. However, no discrimination between the closely
      related species Acetobacter malorum and Acetobacter cerevisiae was possible. As
      previously described, 16S-23S rRNA gene internal transcribed spacer (ITS) region
      phylogenetic analysis was required to classify isolates as one of those species.
      These two species were the most frequently occurring, accounting for more than
      60% of the isolates. For typing the AAB isolates, both the Enterobacterial
      Repetitive Intergenic Consensus (ERIC)-PCR and (GTG)5-PCR techniques gave similar
      resolution. A total of 60 profiles were identified. Thirteen of these profiles
      were found in more than one vineyard, and only one profile was found on two
      different islands (Tenerife and La Palma).

PMID- 21903290
TI  - Effect of dilution rate and nutrients addition on the fermentative capability and
      synthesis of aromatic compounds of two indigenous strains of Saccharomyces
      cerevisiae in continuous cultures fed with Agave tequilana juice.
AB  - Knowledge of physiological behavior of indigenous tequila yeast used in
      fermentation process is still limited. Yeasts have significant impact on the
      productivity fermentation process as well as the sensorial characteristics of the
      alcoholic beverage. For these reasons a better knowledge of the physiological and
      metabolic features of these yeasts is required. The effects of dilution rate,
      nitrogen and phosphorus source addition and micro-aeration on growth,
      fermentation and synthesis of volatile compounds of two native Saccharomyces
      cerevisiae strains, cultured in continuous fed with Agave tequilana juice were
      studied. For S1 and S2 strains, maximal concentrations of biomass, ethanol,
      consumed sugars, alcohols and esters were obtained at 0.04 h-1. Those
      concentrations quickly decreased as D increased. For S. cerevisiae S1 cultures
      (at D=0.08 h-1) supplemented with ammonium phosphate (AP) from 1 to 4 g/L,
      concentrations of residual sugars decreased from 29.42 to 17.60 g/L and ethanol
      increased from 29.63 to 40.08 g/L, respectively. The S1 culture supplemented with
      AP was then micro-aerated from 0 to 0.02 vvm, improving all the kinetics
      parameters: biomass, ethanol and glycerol concentrations increased from 5.66,
      40.08 and 3.11 g/L to 8.04, 45.91 and 4.88 g/L; residual sugars decreased from
      17.67 g/L to 4.48 g/L; and rates of productions of biomass and ethanol, and
      consumption of sugars increased from 0.45, 3.21 and 7.33 g/L.h to 0.64, 3.67 and
      8.38 g/L.h, respectively. Concentrations of volatile compounds were also
      influenced by the micro-aeration rate. Ester and alcohol concentrations were
      higher, in none aerated and in aerated cultures respectively.

PMID- 21903292
TI  - Physicochemical controls on initiation and evolution of desiccation cracks in
      sand-bentonite mixtures: X-ray CT imaging and stochastic modeling.
AB  - The shrink-swell behavior of active clays in response to changes in
      physicochemical conditions creates great challenges for construction of
      geotechnical barriers for hazardous waste isolation, and is of significant
      importance for management of agricultural and natural resources. Initiation and
      evolution of desiccation cracks in active clays are strongly dependent on
      physicochemical initial and boundary conditions. To investigate effects of
      bentonite content (20, 40, 60%), pore fluid chemistry (0.05 and 0.5M NaCl) and
      drying rates (40 and 60 degrees C) on cracking behavior, well-controlled
      dehydration experiments were conducted and X-ray Computed Tomography (CT) was
      applied to visualize and quantify geometrical features of evolving crack
      networks. A stochastic model based on the Fokker-Plank equation was adopted to
      describe the evolution of crack aperture distributions (CAD) and to assess the
      impact of physicochemical factors on cracking behavior. Analyses of crack
      porosity and crack specific surface area showed that both clay content and
      temperature had larger impact on cracking than pore fluid concentration. More
      cracks formed at high bentonite contents (40 and 60%) and at high drying rate (60
      degrees C). The drift, diffusion and source terms derived from stochastic
      analysis indicated that evaporative demand had greater influence on the dynamics
      of the CAD than solution chemistry.

PMID- 21903291
TI  - Longitudinal ethnic differences in multiple cardiovascular risk factor control in
      a cohort of US adults with diabetes.
AB  - AIM: To examine longitudinal differences in multiple cardiovascular risk factor
      control (glycemia, blood pressure, and lipids) by race/ethnicity. METHODS: Data
      were analyzed on a cohort of 11,203 veterans with type 2 diabetes. Primary
      outcome was odds of none of the risk factors out of control vs. having at least
      one out of control (HbA1c>8.0%, BP>140/90 mmHg, and LDL>100mg/dL). Secondary
      outcome was odds of having none out of control vs. having one, two or three risk
      factors out of control, respectively. Generalized linear mixed models assessed
      the relationship between race/ethnicity and multiple risk factor control adjusted
      for covariates. RESULTS: Adjusted models for primary outcome showed that NHB had
      two-fold (95%CI 1.8-2.3) and Hispanics had 48% higher (95%CI 1.3-1.7) odds of
      multiple risk factors out of control over time compared to NHW. Adjusted models
      for secondary outcome showed that NHB and Hispanics also had higher odds of
      having one, two, and three risk factors out of control over time compared to NHW.
      CONCLUSIONS: Ethnic minority veterans with diabetes are less likely to have
      multiple cardiovascular risk factor control over time compared to whites. Thus,
      greater risk reduction efforts are needed to reduce the heavier disease burden
      among ethnic minorities.

PMID- 21903293
TI  - Study of biomaterial-induced macrophage activation, cell-mediated immune response
      and molecular oxidative damage in patients with dermal bioimplants.
AB  - Several soft-tissue dermal fillers have been reported to provoke immunogenicity
      and may cause adverse reactions despite claims regarding their safety. This study
      aimed to assess biomaterial-induced macrophage activation, cell-mediated immune
      response and oxidative stress in 169 patients with dermal bioimplants. To this
      end, we analysed plasma concentrations of myeloperoxidase (MPO), the chitinase
      like proteins chitotriosidase and YKL-40 and molecular oxidative damage. The
      present study shows, for the first time, that the components of innate immunity:
      chitotriosidase and YKL-40, are significantly higher in patients with certain
      bioimplants and these markers of monocyte/macrophage activation rose
      progressively as adverse reactions (AR) evolved. Plasma MPO levels increased 4
      fold in filler users with AR and 3-fold in those without. Analysis by filler type
      showed subjects injected with calcium hydroxylapatite, methacrylate, acrylamides
      and silicone to have values significantly above those of non-filler subjects for
      at least two plasma biomarkers, probably because the afore-mentioned biomaterials
      are permanent and prone to trigger AR in the long term. By contrast, hyaluronic
      acid alone elicited little immune response. Plasma concentrations of markers of
      oxidative damage to lipids and proteins were found to be significantly higher in
      users of four of the nine dermal fillers studied. These diffusible products of
      molecular peroxidation would stem from the reaction catalysed by MPO that
      generates potent oxidants, leading to cell oxidative damage which, in turn, may
      exert deleterious effects on the organism. Overall, the results of this study on
      the effects of a range of dermal fillers point to chronic activation of the
      immune response mediated by macrophages and PMNs. The increases in plasma of MPO,
      chitotriosidase and YKL-40 proteins and products of macromolecular peroxidation
      suggests that these molecules could serve as blood-based biochemical markers and
      alert to the risk of chronic immune system activation and development of adverse
      events that may arise from the use of certain bioimplants.

PMID- 21903294
TI  - IL-12 inhibits the TGF-beta-dependent T cell developmental programs and skews the
      TGF-beta-induced differentiation into a Th1-like direction.
AB  - The development and differentiation of T helper (Th) cell subsets is a highly
      plastic process which is strictly regulated by cytokines. Here we show that the
      transforming growth factor beta (TGF-beta)-dependent differentiation programs are
      negatively regulated by interleukin-12 (IL-12). The development of TGF-beta
      induced regulatory T cells (iTregs) or TGF-beta/IL-6 activated Th17 cells from
      purified mouse CD4(+)CD25(-) T cells, stimulated with monoclonal antibody anti
      CD3, was abrogated in the presence of IL-12 and a different developmental program
      was established. On the molecular level, IL-12 inhibited the expression of the
      lineage specific transcription factors Foxp3 and RORgammat in developing Tregs
      and Th17 cells, respectively. Moreover, IL-12 was able to alter the development
      of iTregs and Th17 cells even when added to the differentiating cells after 48h
      of the culture. The cells activated in the presence of TGF-beta and IL-12 had an
      increased expression of the Th1 transcription factor T-bet, produced Th1
      cytokines interferon gamma and IL-2 and expressed IL-18 receptor and C-C
      chemokine receptor type 5 which are the phenotypic markers characteristic for Th1
      cells. Furthermore, the cells activated in the presence of both TGF-beta and IL
      12, and not of TGF-beta only, stimulated macrophages to produce nitric oxide.
      Altogether, these results indicate that IL-12 is a superior cytokine that has the
      ability to skew the already ongoing TGF-beta-dependent iTreg or Th17
      developmental program into Th1-like direction.

PMID- 21903295
TI  - Exogenous ornithine is an effective precursor and the delta-ornithine amino
      transferase pathway contributes to proline accumulation under high N recycling in
      salt-stressed cashew leaves.
AB  - The role of the delta-ornithine amino transferase (OAT) pathway in proline
      synthesis is still controversial and was assessed in leaves of cashew plants
      subjected to salinity. The activities of enzymes and the concentrations of
      metabolites involved in proline synthesis were examined in parallel with the
      capacity of exogenous ornithine and glutamate to induce proline accumulation.
      Proline accumulation was best correlated with OAT activity, which increased 4
      fold and was paralleled by NADH oxidation coupled to the activities of OAT and
      Delta(1)-pyrroline-5-carboxylate reductase (P5CR), demonstrating the potential of
      proline synthesis via OAT/P5C. Overall, the activities of GS, GOGAT and aminating
      GDH remained practically unchanged under salinity. The activity of P5CR did not
      respond to NaCl whereas Delta(1)-pyrroline-5-carboxylate dehydrogenase was
      sharply repressed by salinity. We suggest that if the export of P5C from the
      mitochondria to the cytosol is possible, its subsequent conversion to proline by
      P5CR may be important. In a time-course experiment, proline accumulation was
      associated with disturbances in amino acid metabolism as indicated by large
      increases in the concentrations of ammonia, free amino acids, glutamine, arginine
      and ornithine. Conversely, glutamate concentrations increased moderately and only
      within the first 24h. Exogenous feeding of ornithine as a precursor was very
      effective in inducing proline accumulation in intact plants and leaf discs, in
      which proline concentrations were several times higher than glutamate-fed or salt
      treated plants. Our data suggest that proline accumulation might be a consequence
      of salt-induced increase in N recycling, resulting in increased levels of
      ornithine and other metabolites involved with proline synthesis and OAT activity.
      Under these metabolic circumstances the OAT pathway might contribute
      significantly to proline accumulation in salt-stressed cashew leaves.

PMID- 21903296
TI  - [Preconceived ideas, paradoxes, and new concepts in retinal vein occlusion].
AB  - Retinal vein occlusion is the second cause of vascular retinopathy after diabetic
      retinopathy and often leads to poor visual outcome. In a simplified form, the
      authors attempt to rectify a number of preconceived ideas about retinal vein
      occlusion and introduce new concepts in order to assist in the understanding of
      their mechanisms. Various paradoxes are explained, such as the presence of
      arterial risk factors in this venous disorder, the atypical combination of
      retinal ischemia and the absence of vascular non-perfusion on fluorescein
      angiography, the fact that macular edema is larger in the ischemic form than in
      the well-perfused form, the aggravating role of contraceptive hormonal therapy,
      the protective role of substitutive hormonal therapy, etc. The current
      controversies are underlined: the seasonal onset of the disease, the role of
      vasodilator treatment, the place of etiologic screening, and the significance of
      prepapillary loops. Lastly, the authors summarize important basics about
      treatment modalities, even if there is not yet consensus on the treatment of
      retinal vein occlusion.

PMID- 21903298
TI  - [Severe hemolytic crisis and multiorgan failure secondary to Clostridium
      perfringens infection].

PMID- 21903297
TI  - Clinical presentation of dengue among patients admitted to the adult emergency
      department of a tertiary care hospital in Martinique: implications for triage,
      management, and reporting.
AB  - STUDY OBJECTIVE: During dengue epidemics, emergency physicians face large numbers
      of patients with acute febrile illness. Triage algorithms and appropriate
      reporting systems are useful to manage patients and prioritize resources. We
      identify possible adaptations to these systems to improve the management of
      patients during epidemics. METHODS: In a prospective observational study in the
      adult emergency department (ED) of a tertiary care hospital, we enrolled all
      patients with febrile illness and a confirmed diagnosis of dengue (ribonucleic
      acid identification). We then retrospectively classified cases according to the
      initial clinical presentation at the ED. RESULTS: We enrolled 715 patients (332
      male patients), aged 14 to 91 years (median 35 years). Severe illness was
      documented in 332 cases (46.4%) and was mostly caused by serotype 2, or a
      secondary infection of any serotype. Severe forms included dengue hemorrhagic
      fever or dengue shock syndrome (104/332; 31.3%), severe bleeding (9/332; 2.7%),
      and acute organ failure (56/332; 16.9%). The other patients with severe illness
      (171/332; 51.5%) presented with symptoms of presyncope, intense weakness,
      prolonged gastrointestinal symptoms, and hypotension. This presentation was
      common during epidemics and appeared to be associated with dehydration and
      electrolyte loss that improved markedly within 24 hours with saline solution
      infusion. This group did not have evidence of plasma leakage, although similar
      features were observed in patients with dengue hemorrhagic fever/dengue shock
      syndrome. CONCLUSION: Dengue has a wide range of clinical presentations in the
      ED. Many patients who appear seriously ill on presentation will respond to
      intravenous fluids.

PMID- 21903299
TI  - [Biological mechanisms involved in the spread of traumatic brain damage].
AB  - Traumatic brain injury (TBI) is a worldwide health problem that is especially
      prevalent in young adults. It is characterized by one or more primary injury
      foci, with secondary spread to initially not compromised areas via cascades of
      inflammatory response, excitotoxicity, energy failure conditions, and
      amplification of the original tissue injury by glia. In theory, such progression
      of injury should be amenable to management. However, all neuroprotective drug
      trials have failed, and specific treatments remain lacking. These negative
      results can be explained by a neuron centered approach, excluding the
      participation of other cell types and pathogenic mechanisms. To change this
      situation, it is necessary to secure a better understanding of the biological
      mechanisms determining damage progression or spread. We discuss the biological
      mechanisms involved in the progression of post-trauma tissue damage, including
      the general physiopathology of TBI and cellular mechanisms of secondary damage
      such as inflammation, apoptosis, cell tumefaction, excitotoxicity, and the role
      of glia in damage propagation. We highlight the role of glia in each cellular
      mechanism discussed. Therapeutic approaches related to the described mechanisms
      have been included. The discussion is completed with a working model showing the
      convergence of the main topics.

PMID- 21903300
TI  - Detection of phylogenetic group B1 Escherichia coli by multiplex PCR: description
      of a new amplification pattern.

PMID- 21903301
TI  - [Effect of the time between symptom onset, swabbing and testing on the detection
      of influenza virus].
AB  - BACKGROUND: Influenza surveillance requires the collection of nasopharyngeal
      swabs in Primary Care for testing in reference laboratories. We evaluated the
      influence on the laboratory results of the time since the onset of symptoms to
      swabbing (TSS) and from then until laboratory processing (TSL). METHODS: We
      analysed swabs collected in the Sentinel Network of Navarra during the 2009-2010
      influenza season. The samples were kept refrigerated until analysed by RT-PCR and
      viral culture. We analysed the percentage of positive swabs to influenza virus in
      accordance with the TSS and TSL by logistic regression. RESULTS: From a total of
      937 swabs, 373 (40%) were positive for influenza by RT-PCR. The TSS ranged from 0
      15 days. In the adjusted analysis by period, laboratory and age, having a
      positive influenza culture decreased to less than half when the TSS was 4-5 days
      (OR=0.47; 95% CI, 0.24-0.94), and having a positive RT-PCR decreased when the TSS
      was 5 days or more (OR=0.24, 95% CI, 0.09-0.65). TSL does not significantly
      affect the result of the RT-PCR (OR by each day=0.96; 95% CI, 0.88-1.04), or the
      result of the viral culture (OR by each day=0.97, 95% CI, 0.89-1.06).
      CONCLUSIONS: A TSS over 3 days reduced the likelihood of confirmation of
      influenza, affecting the viral culture more than the RT-PCR. A TSL within a range
      of two weeks had no significant effect on the results of the RT-PCR or the viral
      culture.

PMID- 21903302
TI  - [Persistent inflammation of the nasal dorsum in a patient with rheumatoid
      arthritis treated with infliximab].

PMID- 21903303
TI  - [Health care in dementia: satisfaction and needs of the caregiver].
AB  - INTRODUCTION: Primary care (PC) and general neurology clinics (NC) assume the
      leading role in the health care of patients with dementia. There are hardly any
      studies on the satisfaction of the caregiver at these settings of health care.
      METHODS: A questionnaire was designed and distributed to 75 caregivers of
      patients with dementia who were reviewed in an NC and who had been referred from
      PC. The questionnaire included questions associated with the care, the use of
      services, and satisfaction. Sociodemographic and clinical variables were also
      collected. The results of the questionnaire are described and a simple
      correlation analysis (Spearman r) was performed to determine the factors
      associated with satisfaction. RESULTS: The majority of carers were sons or
      daughters (60%) or spouses (31%), of which 73% were women. The service most used
      was home help (36%), but 41% of patients had no services available. Satisfaction
      was high (84% quite or very satisfied with PC, 97% quite or very satisfied with
      the NC, P<.01). A greater number of years giving care was associated with a lower
      satisfaction with PC ((r=-0.37, P<.005), while institutionalisation was
      associated with a lower satisfaction with the NC (r=-0.30, P<.01). CONCLUSIONS:
      In a context of a scarcity of resources, the satisfaction of the caregivers of
      patients with dementia, as regards health care, was high, possibly due to the
      motivation of the health professionals and the positive attitude of the
      caregivers themselves.

PMID- 21903304
TI  - Synthesis, fluorescence and biodistribution of a bone-targeted near-infrared
      conjugate.
AB  - Enhanced imaging of early-stage bone abnormalities, such as primary tumors or
      metastases is highly required as the widely-used bone scan frequently lacks the
      desired sensitivity. Near IR (NIR) fluorescence imaging affords high contrast and
      enhanced sensitivity, as body tissue expresses minimal autofluorescence at NIR
      range (600-1200 nm). Indocyanine green (ICG), a biocompatible NIR dye, is widely
      used in the imaging of various organs, such as liver, heart and blood
      circulation. We report the preparation and in-vivo testing of a bone-targeting
      ICG derivative, in comparison to the parent molecule(s). Since ICG itself is
      chemically unreactive, and could not form conjugates, we prepared two novel ICG
      conjugatable derivatives. The overall ICG structure was maintained while only a
      replacement of one or two sulfonate groups with carboxylic acids resulted in new
      linkers for covalent binding to biomolecules. These derivatives were evaluated
      for their fluorescence and biodistribution in comparison to ICG and were found to
      be comparable. One of the novel ICG-derivatives was conjugated to a bone
      targeting moiety and this new compound was found to bind to growing regions of
      the skeleton, and emit fluorescence for as long as two weeks in young mice.

PMID- 21903305
TI  - Top tips for PhD thesis examination: nurse clinicians, researchers and novices.
AB  - Interestingly, there are very few guidelines in the literature to assist novice
      nurse PhD examiners. In this paper, we aim to provide information to nurses,
      researchers or early career academics who have little experience in assessing a
      university thesis. The article provides background information about recent
      changes in the university sector; overviews some research on experienced
      examiners views; presents factors that differentiate between high and low quality
      PhD theses; and outlines some pointers that may be useful when marking at the
      doctoral level.

PMID- 21903306
TI  - Qualitative comparison of curricula in oral and maxillofacial surgery training.
      Part 2: oral surgery.
AB  - A comparison between the curricula for specialist training in oral surgery (OS),
      and oral and maxillofacial surgery (OMFS) illustrates the overlap between the two
      specialties. We identified and compared relevant curricula for OMFS with
      competencies in the OS specialist-training curriculum using a qualitative
      assessment to establish the degree of overlap. All competencies within the OS
      curriculum are covered by OMFS curricula, and 21 of 96 OMFS clinical competencies
      are covered by OS core competencies. The majority of OMFS competencies are unique
      and are not directly comparable with those in the OS curriculum. Knowledge of
      this overlap may help to avoid unnecessary duplication in the training of those
      who wish to transfer specialty.

PMID- 21903307
TI  - First-time mothers' perspectives on relationships with and between midwives and
      doctors: insights from a qualitative study of giving birth in New Zealand.
AB  - OBJECTIVE: to explore the experience of giving birth for first-time New Zealand
      mothers. DESIGN: qualitative methodology was employed to obtain an in-depth
      insight into the birth experience using semi-structured interviews conducted face
      to-face 11 days to 16 weeks (median 13.5 weeks) after giving birth were audio
      recorded and transcribed verbatim. SETTING: the interviews were of a small group
      of New Zealand mothers. PARTICIPANTS: ten first-time mothers aged 24-38 years
      (median 31.5 years) participated. MEASUREMENTS: transcripts were analysed using a
      phenomenological form of thematic analysis. FINDINGS: a core theme was
      relationship issues. Two subthemes were delineated: lack of relationship between
      mothers and midwives and doctors; and the conflict between midwives and doctors.
      KEY CONCLUSIONS: personal, caring and co-operative relationships with all
      maternity care professionals were basic to New Zealand mothers feeling good about
      their birth experience. IMPLICATIONS FOR PRACTISE: relationships, with and
      between, all maternity care professionals merit further investigation in an
      effort to optimise birth satisfaction.

PMID- 21903308
TI  - The perspectives of Australian midwifery academics on barriers and enablers for
      simulation in midwifery education in Australia: a focus group study.
AB  - OBJECTIVE: to describe Australian midwifery academics' perceptions of the current
      barriers and enablers for simulation in midwifery education in Australia and the
      potential and resources required for simulation to be increased. DESIGN: a series
      of 11 focus groups/interviews were held in all states and territories of
      Australia with 46 participating academics nominated by their heads of discipline
      from universities across the country. FINDINGS: three themes were identified
      relating to barriers to the extension of the use of simulated learning
      environments (SLEs) ('there are things that you can't simulate'; 'not having the
      appropriate resources'; and professional accreditation requirements) and three
      themes were identified to facilitate SLE use ('for the bits that you're not
      likely to see very often in clinical'; ['for students] to figure something out
      before [they] get to go out there and do it on the real person'; and good
      resources and support). KEY CONCLUSION: although barriers exist to the adoption
      and spread of simulated learning in midwifery, there is a long history of
      simulation and a great willingness to enhance its use among midwifery academics
      in Australia. IMPLICATIONS FOR PRACTICE: while some aspects of midwifery practice
      may be impossible to simulate, more collaboration and sharing in the development
      and use of simulation scenarios, equipment, space and other physical and
      personnel resources would make the uptake of simulation in midwifery education
      more widespread. Students would therefore be exposed to the best available
      preparation for clinical practice contributing to the safety and quality of
      midwifery care.

PMID- 21903309
TI  - Influence of assembly procedure and material combination on the strength of the
      taper connection at the head-neck junction of modular hip endoprostheses.
AB  - BACKGROUND: A stable fixation between femoral head and endoprosthesis taper is
      necessary to prevent relative motions and corrosion at the taper junction.
      Although the importance of the component assembly has been recognised, no
      definitive instructions are available. The purpose of this study was to assess
      the influence of assembly force, assembly tool and number of hammer strokes on
      the taper junction strength of various material combinations. METHODS: Co-Cr29-Mo
      (n=10) and Ti-6Al-4V (n=10) neck tapers were assembled with Co-Cr and Al(2)O(3)
      ceramic heads either by push-on or by impaction with single or multiple hammer
      blows. The strength of the taper-head connection was evaluated by measuring the
      head pull-off forces according to ISO 7206-10 and the turn-off moment capacity.
      FINDINGS: The taper strength linearly increased with assembly forces (P<0.001).
      Co-Cr heads combined with Co-Cr tapers showed significantly lower pull-off forces
      and turn-off moments than the combination with Ti tapers (0.001<P<0.025).
      Multiple impaction did not increase taper strength (0.063 <P<0.995). Ceramic and
      Co-Cr heads showed similar fixation patterns on Ti tapers. Turn-off moments
      varied between 6 Nm and 19 Nm, dependent on material combination and assembly
      force. INTERPRETATION: It is suggested that sufficient head-taper junction
      strength in all bearing conditions is achieved by impaction forces of at least 4
      kN. A single impact is sufficient to achieve fixation. Special attention should
      be paid to the assembly of Co-Cr heads on Co-Cr tapers.

PMID- 21903310
TI  - Anthropogenic and naturally occurring polybrominated phenolic compounds in the
      blood of cetaceans stranded along Japanese coastal waters.
AB  - We determined the residue levels and patterns of hydroxylated polybrominated
      diphenyl ethers (OH-PBDEs), and related compounds, such as PBDEs, methoxylated
      PBDEs (MeO-PBDEs), and bromophenols (BPhs) in the blood of eleven cetacean
      species stranded along the Japanese coasts. The dominant OH- and MeO-PBDE isomers
      found in all cetaceans were 6OH-BDE47 and 6MeO-BDE47. Additionally, 2,4,6-triBPh
      was dominant isomer in all cetaceans. In contrast, specific differences in the
      distribution of para- and meta- OH-PBDE isomers and some BPhs (potential PBDEs
      metabolites) were found among the cetaceans. Residue levels of SigmaMeO-PBDEs and
      6OH-BDE47 + 2'OH-BDE68, and 2,4,6-triBPh and 6OH-BDE47 + 2'OH-BDE68 showed a
      significant positive correlation. These results may suggest that the large
      percentages of OH-PBDEs, MeO-PBDEs and 2,4,6-triBPh might share common source
      (i.e. biosynthesis by marine organisms), or metabolic pathway in cetacean
      species. Significant correlations were found between the concentrations of BDE99
      and 2,4,5-triBPh. This result suggested that 2,4,5-triBPh in cetaceans could be a
      metabolite of BDE99.

PMID- 21903311
TI  - Mercury exposure in terrestrial birds far downstream of an historical point
      source.
AB  - Mercury (Hg) is a persistent environmental contaminant found in many freshwater
      and marine ecosystems. Historical Hg contamination in rivers can impact the
      surrounding terrestrial ecosystem, but there is little known about how far
      downstream this contamination persists. In 2009, we sampled terrestrial forest
      songbirds at five floodplain sites up to 137 km downstream of an historical
      source of Hg along the South and South Fork Shenandoah Rivers (Virginia, USA). We
      found that blood total Hg concentrations remained elevated over the entire
      sampling area and there was little evidence of decline with distance. While it is
      well known that Hg is a pervasive and long-lasting aquatic contaminant, it has
      only been recently recognized that it also biomagnifies effectively in floodplain
      forest food webs. This study extends the area of concern for terrestrial habitats
      near contaminated rivers for more than 100 km downstream from a waterborne Hg
      point source.

PMID- 21903312
TI  - Uptake of 17beta-estradiol and biomarker responses in brown trout (Salmo trutta)
      exposed to pulses.
AB  - In streams, chemicals such as 17beta-estradiol (E2) are likely to occur in
      pulses. We investigated uptake and biomarker responses in juvenile brown trout
      (Salmo trutta) of 3- or 6-h pulses of concentrations up to 370 ng E2 L(-1).
      Uptake by the fish was estimated from disappearance of E2 from tank water. A
      single 6-h pulse of 370 ng E2 L(-1) increased the plasma vitellogenin
      concentration, liver Eralpha- and vitellogenin-mRNA. Exposure to 150-160 ng E2 L(
      1) for 6 h increased vitellogenin in one experiment but not in another. Two 6-h
      pulses had a larger effect one pulse. Brown trout in the size range 24-74 g took
      up E2 linearly with time and exposure concentration with a concentration ratio
      rate of 20.2 h(-1). In conclusion, the threshold for induction of estrogenic
      effects in juvenile brown trout at short term pulse exposure appears to be in the
      range 150-200 ng E2 L(-1).

PMID- 21903313
TI  - Planting woody crops on dredged contaminated sediment provides both positive and
      negative effects in terms of remediation.
AB  - There is currently a requirement for studies focusing on the long-term
      sustainability of phytoremediation technologies. Trace element uptake by Salix,
      Populus and Alnus species planted in dredged contaminated canal sediment and
      concentrations in sediment and pore waters were investigated, eight years after a
      phytoremediation trial was initiated in NW England. Soil biological activity was
      also measured using invertebrate and microbial assays to determine soil quality
      improvements. Zinc was the dominant trace metal in foliage and woody stems, and
      the most mobile trace element in sediment pore water (~14 mg l(-1)). Biological
      activity had improved; earthworm numbers had increased from 5 to 24, and the QBS
      index (an index of microarthropod groups in soil) had increased from 70 to 88. It
      is concluded that biological conditions had improved and natural processes appear
      to be enhancing soil quality, but there remains a potential risk of trace element
      transfer to the wider environment.

PMID- 21903314
TI  - PBDEs, PCBs, and DDE in eggs and their impacts on aplomado falcons (Falco
      femoralis) from Chihuahua and Veracruz, Mexico.
AB  - Eggs from aplomado falcons (Falco femoralis septentrionalis) nesting in Chihuahua
      and Veracruz, Mexico, were analyzed for organochlorine pesticides, PCBs, and
      PBDEs. p,p'-DDE was the only organochlorine found in all eggs at concentrations
      ranging from 0.13 to 7.85 MUg/g wet weight. PCBs ranged from 0.04 to 2.80 MUg/g
      wet weight and PBDEs from 62 to 798 ng/g lipid weight. DDE concentrations in eggs
      were not significantly different among regions; however, PCBs were significantly
      greater (P = 0.015) in Tinaja Verde, Chihuahua than in the other three regions.
      Also, PBDEs were significantly higher (P < 0.0001) in eggs from Veracruz than in
      those from Chihuahua. DDE concentrations in eggs were much lower than those
      associated with eggshell thinning. PBDEs and PCBs were lower than those reported
      in raptors from industrialized countries. Overall, contaminant concentrations
      observed suggest no likely impact on hatching success. The PBDE concentrations
      are among the first to be reported in raptor species in Mexico.

PMID- 21903315
TI  - Using stable lead isotopes to trace heavy metal contamination sources in
      sediments of Xiangjiang and Lishui Rivers in China.
AB  - Lead isotopes and heavy metal concentrations were measured in two sediment cores
      sampled in estuaries of Xiangjiang and Lishui Rivers in Hunan province, China.
      The presence of anthropogenic contribution was observed in both sediments,
      especially in Xiangjiang sediment. In the Xiangjiang sediment, the lower
      (206)Pb/(207)Pb and higher (208)Pb/(206)Pb ratio, than natural Pb isotope
      signature (1.198 and 2.075 for (206)Pb/(207)Pb and (208)Pb/(206)Pb,
      respectively), indicated a significant input of non-indigenous Pb with low
      (206)Pb/(207)Pb and high (208)Pb/(206)Pb. The corresponding concentrations of
      heavy metals (As, Cd, Zn, Mn and Pb) were much higher than natural values,
      suggesting the contaminations of heavy metals from extensive ore-mining
      activities in the region.

PMID- 21903316
TI  - Systematic barriers to the effective delivery of home dialysis in the United
      States: a report from the Public Policy/Advocacy Committee of the North American
      Chapter of the International Society for Peritoneal Dialysis.
AB  - Home dialysis, currently underused in the United States compared with other
      industrialized countries, likely will benefit from the newly implemented US
      prospective payment system. Not only is home dialysis less expensive from the
      standpoint of pure dialysis costs, but overall health system costs may be
      decreased by more subtle benefits, such as reduced transportation. However, many
      systematic barriers exist to the successful delivery of home dialysis. We
      organized these barriers into the categories of educational barriers (patient and
      providers), governmental/regulatory barriers (state and federal), and barriers
      specifically related to the philosophies and business practices of dialysis
      providers (eg, staffing, pharmacies, supplies, space, continuous quality
      improvement practices, and independence). All stakeholders share the goal of
      delivering home dialysis therapies in the most cost- and clinically effective and
      least problematic manner. Identification and recognition of such barriers is the
      first step. In addition, we have suggested action plans to stimulate the kidney
      community to find even better solutions so that collectively we may overcome
      these barriers.

PMID- 21903317
TI  - Autosomal dominant mutation in the signal peptide of renin in a kindred with
      anemia, hyperuricemia, and CKD.
AB  - Homozygous or compound heterozygous mutations in renin (REN) cause renal tubular
      dysgenesis, which is characterized by death in utero due to kidney failure and
      pulmonary hypoplasia. The phenotype resembles the fetopathy caused by angiotensin
      converting enzyme inhibitor or angiotensin receptor blocker intake during
      pregnancy. Recently, heterozygous REN mutations were shown to result in early
      onset hyperuricemia, anemia, and chronic kidney disease (CKD). To date, only 3
      different heterozygous REN mutations have been published. We report mutation
      analysis of the REN gene in 39 kindreds with hyperuricemia and CKD who previously
      tested negative for mutations in the UMOD (uromodulin) and HNF1B (hepatocyte
      nuclear factor 1beta) genes. We identified one kindred with a novel thymidine to
      cytosine mutation at position 28 in the REN complementary DNA, corresponding to a
      tryptophan to arginine substitution at amino acid 10, which is found within the
      signal sequence (c.28T>C; p.W10R). On this basis, we conclude that REN mutations
      are rare events in patients with CKD. Within the kindred, we found affected
      individuals over 4 generations who carried the novel REN mutation and were
      characterized by significant anemia, hyperuricemia, and CKD. Anemia was severe
      and disproportional to the degree of decreased kidney function. Because all
      heterozygous REN mutations that have been described are localized in the signal
      sequence, screening of the REN gene for patients with CKD with hyperuricemia and
      anemia may best be focused on sequencing of exon 1, which encodes the signal
      peptide.

PMID- 21903318
TI  - The role of daily mobility in mental health inequalities: the interactive
      influence of activity space and neighbourhood of residence on depression.
AB  - The literature reports an association between neighbourhood deprivation and
      individual depression after adjustment for individual factors. The present paper
      investigates whether vulnerability to neighbourhood features is influenced by
      individual "activity space" (i.e., the space within which people move about or
      travel in the course of their daily activities). It can be assumed that a
      deprived residential environment can exert a stronger influence on the mental
      health of people whose activity space is limited to their neighbourhood of
      residence, since their exposure to their neighbourhood would be greater.
      Moreover, we studied the relationship between activity space size and depression.
      A limited activity space could indeed reflect spatial and social confinement and
      thus be associated with a higher risk of being depressed, or, conversely, it
      could be linked to a deep attachment to the neighbourhood of residence and thus
      be associated with a lower risk of being depressed. Multilevel logistic
      regression analyses of a representative sample consisting of 3011 inhabitants
      surveyed in 2005 in the Paris, France metropolitan area and nested within 50
      census blocks showed, after adjusting for individual-level variables, that people
      living in deprived neighbourhoods were significantly more depressed that those
      living in more advantaged neighbourhoods. We also observed a statistically
      significant cross-level interaction between activity space and neighbourhood
      deprivation, as they relate to depression. Living in a deprived neighbourhood had
      a stronger and statistically significant effect on depression in people whose
      activity space was limited to their neighbourhood than in those whose daily
      travels extended beyond it. In addition, a limited activity space appeared to be
      a protective factor with regard to depression for people living in advantaged
      neighbourhoods and a risk factor for those living in deprived neighbourhoods. It
      could therefore be useful to take activity space into consideration more often
      when studying the social and spatial determinants of depression.

PMID- 21903319
TI  - Viewing objects and planning actions: on the potentiation of grasping behaviours
      by visual objects.
AB  - How do humans interact with tools? Gibson (1979) suggested that humans perceive
      directly what tools afford in terms of meaningful actions. This "affordances"
      hypothesis implies that visual objects can potentiate motor responses even in the
      absence of an intention to act. Here we explore the temporal evolution of motor
      plans afforded by common objects. We presented objects that have a strong
      significance for action (pinching and grasping) and objects with no such
      significance. Two experimental tasks involved participants viewing objects
      presented on a computer screen. For the first task, they were instructed to
      respond rapidly to changes in background colour by using an apparatus mimicking
      precision and power grip responses. For the second task, they received
      stimulation of their primary motor cortex using transcranial magnetic stimulation
      (TMS) while passively viewing the objects. Muscular responses (motor evoked
      potentials: MEPs) were recorded from two intrinsic hand muscles (associated with
      either a precision or power grip). The data showed an interaction between type of
      response (or muscle) and type of object, with both reaction time and MEP measures
      implying the generation of a congruent motor plan in the period immediately after
      object presentation. The results provide further support for the notion that the
      physical properties of objects automatically activate specific motor codes, but
      also demonstrate that this influence is rapid and relatively short lived.

PMID- 21903320
TI  - Advances in the diagnosis of tuberculosis infection.
AB  - One-third of the world-wide population currently presents latent tuberculosis
      infection (LTI). In Spain, TB is situated as the third disease of mandatory
      notification. The standard technique for the diagnosis of ITL is the tuberculin
      test (PPD), although its most important drawback is its specificity since the
      proteins used are not specific for Mycobacterium tuberculosis. In recent years,
      research has been done and new diagnostic methods have been approved based on the
      in vitro quantification of the immune cell response, the so-called interferon
      gamma release assays (IGRA). Compared with PPD, the main difference is that IGRAs
      detect the release of interferon-gamma in response to specific tuberculous
      antigens. In the absence of a true reference test for the diagnosis of
      tuberculosis infection, it is difficult to establish the sensitivity and
      specificity of these new diagnostic techniques. IGRAs have been used in the
      detection of ITL in subjects with immune system alterations (HIV, EEI, IRC,
      rheumatologic diseases) with good results. They are also being extensively used
      in the study of contacts. In recent studies involving serial controls of said
      tests, they were observed to present conversions and reversions that occur after
      exposure to M. tuberculosis. Today and with the current knowledge, it seems that
      IGRAs can complement PPD, but not substitute them.

PMID- 21903321
TI  - Nuclear receptor mRNA expression by HBV in human hepatoblastoma cell lines.
AB  - Recent studies have implicated nuclear receptors (NRs) in the development of
      hepatocarcinogenesis. We assumed that hepatitis B virus (HBV) alters the
      expression of NRs and coregulators, and compared the gene expression profiling
      for 84 NRs and related genes between HpeG2.2.15, which secretes complete HBV
      virion, and HepG2 by real-time RT-PCR with SyBr green. Forty (47.6%) genes were
      upregulated 2-fold or greater, and only 5 (5.9%) were downregulated 2-fold or
      more, in HepG2.2.15 compared to HepG2. These results suggest that HBV affects NRs
      and their related signal transduction, and that they play important roles in
      viral replication and HBV-related hepatocarcinogenesis.

PMID- 21903322
TI  - Cytotoxicity of troglitazone through PPARgamma-independent pathway and p38 MAPK
      pathway in renal cell carcinoma.
AB  - Agonists of peroxisome proliferator-activated receptor gamma (PPARgamma) have
      been examined as chemopreventive and chemotherapeutic agents. The aim was to
      investigate the cytotoxicity of troglitazone (TGZ) and its mechanisms in terms of
      PPARgamma dependency and the p38 mitogen-activated protein kinase (MAPK) pathway
      in three human renal cell carcinoma (RCC) cell lines, 786-O, Caki-2 and ACHN
      cells. TGZ induced apoptosis and exerted cytotoxicity in a PPARgamma-independent
      manner. We demonstrated that TGZ activated the p38 MAPK pathway and was involved
      in the cytotoxicity of TGZ. It was also revealed that TGZ induced G(2)/M cell
      cycle arrest through activation of p38 MAPK.

PMID- 21903323
TI  - Identification of tumoral glial precursor cells in neuroblastoma.
AB  - Neuroblastic tumors (NBT) are composed by neuroblasts and Schwannian-like stroma.
      The origin of these two cell subtypes remains unclear. In this study, we
      describe, a neuroblastic-like subpopulation in neuroblastoma (NB) coexpressing
      GD2 and S100A6, neuroblastic and glial lineage markers respectively. The
      GD2(+)/S100A6(+) neuroblastic subpopulation was found to be enriched in low risk
      NB, distributed around the perivascular niche. Some stromal bundles showed
      GD2(+)/S100A6 costaining. Metastatic bone marrow specimens also showed
      GD2(+)/S100A6(+) cells. During in vitro retinoic acid induced differentiation of
      NB cell lines, rare GD2(+)/S100A6 neuroblatic cells appeared. We conclude that
      GD2(+)/S100A6(+) neuroblasts may represent a tumoral glial precursor
      subpopulation in NBT.

PMID- 21903324
TI  - Targeting p73 in cancer.
AB  - p73 is a member of the p53 family of tumor suppressors. Transactivating isoforms
      of p73 (TAp73) have p53-like, anti-proliferative and pro-apoptotic activities
      that are crucial for an efficient chemotherapy response. In line with this,
      genetic studies in mice have confirmed that TAp73 acts as a tumor suppressor.
      However, in contrast to p53, which is commonly inactivated in human cancer by
      point mutations, the TP73 gene is almost never mutated. Instead, the tumor
      suppressor activity of TAp73 is inhibited through a variety of mechanisms
      including epigenetic silencing and complex formation with inhibitory proteins.
      All these mechanisms have in common that they are in principle reversible and
      therefore amenable to therapeutic intervention. Here, we will review how tumor
      cells control the tumor suppressor activity of TAp73 and discuss possible
      strategies targeting p73 for reactivation.

PMID- 21903325
TI  - Effects of UV irradiation on humic acid removal by ozonation, Fenton and Fe0/air
      treatment: THMFP and biotoxicity evaluation.
AB  - Effects of UV irradiation on humic acid (HA) removal by Fe(0)/air, ozonation and
      Fenton oxidation were investigated. The trihalomethane forming potential (THMFP)
      and toxicity of treated solutions were also evaluated. The experimental
      conditions were ozone of 21 mg min(-1), H(2)O(2) of 8 * 10(-4)M, Fe(0) of 20 g L(
      1), air flow of 5 L min(-1), and UVC of 9 W. Results indicated that Fe(0)/air
      rapidly removed HA color (>99%) and COD (90%) within 9 min. 51-81% of color and
      43-50% of COD were removed by ozonation and Fenton oxidation after 60 min. Both
      UV enhanced ozone and Fenton oxidation removed HA, but the Fe(0)/air process did
      not. Spectrum results showed all processes effectively diminished UV-vis spectra,
      except for ozonation. The THMFP of Fe(0)/air-treated solution (114 MUg L(-1)) was
      much lower than those of Fenton- (226 MUg L(-1)) and ozonation-treated solutions
      (499 MUg L(-1)). Fe(0)/air with UV irradiation obviously increased the THMFP of
      treated solution (502 MUg L(-1)). The toxicity results obtained from Vibrio
      fischeri light inhibition test indicated that the toxicity of Fe(0)/air-treated
      solution (5%) was much lower than that of ozonation- (33%) and Fenton-treated
      solutions (31%). Chlorination increased the solution toxicity. The correlation
      between biotoxicity and chloroform in the chlorinated solution was insignificant.

PMID- 21903326
TI  - Nitrogen removal via short-cut simultaneous nitrification and denitrification in
      an intermittently aerated moving bed membrane bioreactor.
AB  - An intermittently aerated moving bed membrane bioreactor (MBMBR) was developed
      and crucial parameters affecting nitrogen removal from wastewater by simultaneous
      nitrification and denitrification via nitrite were investigated, without strict
      control of solids retention time. Changes in the microbiological community and
      distribution in the reactor were monitored simultaneously. The intermittent
      aeration strategy proved effective in achieving nitrition and the chemical oxygen
      demand (COD) to total nitrogen (TN) ratio was an important factor affecting TN
      removal. In the MBMBR, the nitrite accumulation rate reached 79.4% and TN removal
      efficiency averaged at 87.8% with aeration 2 min/mix 4 min and an influent COD/TN
      ratio of 5. Batch tests indicated that under the intermittently aerated mode,
      nitrite-oxidizing bacteria (NOB) were not completely washed out from the reactor
      but NOB activity was inhibited. The intermittently aerated mode had no effect on
      the activities of ammonia-oxidizing bacteria. Fluorescence in situ hybridizations
      (FISH) results also suggested that NOBs remained within the system.

PMID- 21903327
TI  - Rose-like monodisperse bismuth subcarbonate hierarchical hollow microspheres: one
      pot template-free fabrication and excellent visible light photocatalytic activity
      and photochemical stability for NO removal in indoor air.
AB  - Rose-like monodisperse hierarchical (BiO)(2)CO(3) hollow microspheres are
      fabricated by a one-pot template-free method for the first time based on
      hydrothermal treatment of ammonia bismuth citrate and urea in water. The
      microstructure and band structure of the as-prepared (BiO)(2)CO(3) superstructure
      are characterized in detail by X-ray diffraction, Raman spectroscopy, Fourier
      transform-infrared spectroscopy, transmission electron microscopy, scanning
      electron microscopy, N(2) adsorption-desorption isotherms, X-ray photoelectron
      spectroscopy and UV-vis diffuse reflectance spectroscopy. The monodisperse
      hierarchical (BiO)(2)CO(3) microspheres are constructed by the self-assembly of
      single-crystalline nanosheets. The aggregation of nanosheets result in the
      formation of three dimensional hierarchical framework containing mesopores and
      macropores, which is favorable for efficient transport of reaction molecules and
      harvesting of photo-energy. The result reveals the existence of special two-band
      gap structure (3.25 and 2.0 eV) for (BiO)(2)CO(3). The band gap of 3.25 eV is
      intrinsic and the formation of smaller band gap of 2.0 eV can be ascribed to the
      in situ doped nitrogen in lattice. The performance of hierarchical (BiO)(2)CO(3)
      microspheres as efficient photocatalyst are further demonstrated in the removal
      of NO in indoor air under both visible light and UV irradiation. It is found that
      the hierarchical (BiO)(2)CO(3) microspheres not only exhibit excellent
      photocatalytic activity but also high photochemical stability during long term
      photocatalytic reaction. The special microstructure, the high charge separation
      efficiency due to the inductive effect, and two-band-gap structure in all
      contribute to the outstanding photocatalytic activities. The discovery of
      monodisperse hierarchical nitrogen doped (BiO)(2)CO(3) hollow structure is
      significant because of its potential applications in environmental pollution
      control, solar energy conversion, catalysis and other related areas.

PMID- 21903328
TI  - Forebrain medial septum region facilitates nociception in a rat formalin model of
      inflammatory pain.
AB  - The medial septum is anatomically and functionally linked to the hippocampus, a
      region implicated in nociception. However, the role of medial septum in
      nociception remains unclear. To investigate the role of the region in nociception
      in rats, muscimol, a GABA agonist, or zolpidem, a positive allosteric modulator
      of GABA(A) receptors, was microinjected into medial septum to attenuate the
      activity of neurons in the region. Electrophysiological studies in anesthetized
      rats indicated that muscimol evoked a stronger and longer-lasting suppression of
      medial septal-mediated activation of hippocampal theta field activity than
      zolpidem. Similarly, microinjection of muscimol (1 or 2 MUg/0.5 MUl) into the
      medial septum of awake rats suppressed both licking and flinching behaviors in
      the formalin test of inflammatory pain, whereas only the latter behavior was
      affected by zolpidem (8 or 12 MUg/0.5 MUl) administered into the medial septum.
      Interestingly, both drugs selectively attenuated nociceptive behaviors in the
      second phase of the formalin test that are partly driven by central plasticity.
      Indeed, muscimol reduced the second phase behaviors by 30% to 60%, which was
      comparable to the reduction seen with systemic administration of a moderate dose
      of the analgesic morphine. The reduction was accompanied by a decrease in
      formalin-induced expression of spinal c-Fos protein that serves as an index of
      spinal nociceptive processing. The drug effects on nociceptive behaviors were
      without overt sedation and were distinct from the effects observed after septal
      lateral microinjections. Taken together, these findings suggest that the
      activation of medial septum is pro-nociceptive and facilitates aspects of central
      neural processing underlying nociception.

PMID- 21903329
TI  - How is neuropathic cancer pain assessed in randomised controlled trials?

PMID- 21903330
TI  - Giardia duodenalis cyst survival in cattle slurry.
AB  - Giardia duodenalis is a protozoan parasite known to infect animals and humans.
      Zoonotic transmission of G. duodenalis can occur by the consumption of drinking
      water produced from surface water that is contaminated by runoff from manure
      laden fields or pastures. Although it was previously reported that storing solid
      cattle manure decreases G. duodenalis cyst viability, no data are available on
      cyst survival in slurry waste from cattle. In this study the number and the
      viability of G. duodenalis cysts was determined in cattle slurry for up to 90
      days. G. duodenalis cysts were counted in 30 slurry samples with a quantitative
      direct immunofluorescence assay. The geometric mean number of cysts was reduced
      by 77% after 90 days (P<0.0014), although there was substantial variability
      between samples. A fluorogenic dye staining using 4',6'-di-amino-2-phenylindole
      and propidium iodide showed a decreased viability from 45 days onwards, and after
      90 days incubation, only 3% of the cysts were viable. Gerbils and lambs were
      artificially infected with 50 day-old and 90 day-old cysts and faecal excretion
      of G. duodenalis was monitored between 5 and 7 days after infection. Seven days
      after infection the gerbils were euthanized for Giardia trophozoite counts.
      Although one cyst was found in the faeces of one of the gerbils after infection
      with 50 day-old cysts, no trophozoites were recovered from the intestines of any
      gerbil (n=8). Experimental infection of lambs with 10(5)50 day-old and 90 day-old
      slurry cysts caused low cyst excretion in one out of two and one out of three
      lambs, respectively. Together, these data show that storage of cattle slurry for
      90 days greatly reduces the number and viability of G. duodenalis cysts.

PMID- 21903331
TI  - The dermis graft: another autologous option for acute burn wound coverage.
AB  - BACKGROUND: Split-thickness skin autografts are the gold-standard in providing
      permanent acute wound closure in major burns. Split-thickness dermal grafts
      harvested from the same donor site may provide an additional autologous option
      for permanent acute coverage and increase the number of potential autologous
      donor sites. MATERIALS AND METHODS: We performed 16 dermis grafts (DG) harvested
      from the skin of the back in 9 consecutive burn patients. A control donor site
      consisted of an area of adjacent back skin from which a standard split-thickness
      skin graft was harvested. The mean age was 63 years (range 23-79 years). The mean
      initial burn size was 24% TBSA (range 2-40% TBSA). The size of the 16 DG
      recipient wound beds ranged from 20 to 180 cm2, with mean and median sizes of 62
      and 45 cm2, respectively. RESULTS: Dermis graft take was complete in 15/16 cases.
      All grafts recorded >90% epithelialisation by 4 weeks. There was no significant
      difference in dermis graft and control donor site healing times (p value 0.05).
      CONCLUSION: Dermis grafts can provide an additional autologous option for
      permanent coverage in acute major burn wounds without increasing donor site size
      or morbidity.

PMID- 21903332
TI  - Adolescent first lapse following smoking cessation: situation characteristics,
      precipitants and proximal influences.
AB  - Despite increased attention to adolescent smoking cessation, little is known
      about adolescent relapse following a quit attempt. To address this issue, the
      present study was designed to provide initial information regarding the
      characteristics of adolescent lapses to smoking following abstinence. Included in
      the present study were 204 adolescent participants in four independent smoking
      cessation trials. For the full sample, participants averaged 15.99 (1.27) years
      of age; 56% were female and 78% were white. Lapse characteristics and
      precipitants were assessed using the Adolescent Smoking Relapse Review. Three
      domains of the lapse experience were assessed: lapse situation characteristics,
      precipitants of use in the situation, and proximal influences (i.e., potential
      precipitants occurring on the same day, prior to the lapse situation).
      Participant reports indicated that the modal lapse situation occurred in the
      evening while socializing with friends at home. Urges or cravings and social
      pressure were commonly endorsed as occurring in lapse situations. The most
      frequently reported proximal influence was desire for a cigarette, followed by
      abstinence-violation cognitions (okay to smoke occasionally, wanted to see what
      it would be like) and negative emotions. The findings indicate that a broad range
      of factors appear to influence adolescent smoking lapse and commend the value of
      incorporating content relevant to managing social and affective cues, strategies
      for inhibiting the prepotent response to ask for a cigarette, addressing
      cognitions regarding the difficulty of not smoking (i.e., cessation expectancies)
      and combating perceptions of the ability to smoke occasionally.

PMID- 21903333
TI  - ERbeta may contribute to the maintaining of radial glia cells polarity through
      cadherins during corticogenesis.
AB  - Laminar organization of neurons in cerebral cortex is essential for normal brain
      function. Radial glial cells (RGCs), are highly polarized cells that serve as
      neuronal progenitors and as scaffolds for neuronal migration during construction
      of the cerebral cortex. Cadherins (E-cadherin and N-cadherin)-based adherins
      junctions, which anchor apical end-feet of adjacent RGCs to each other at the
      ventricular surface contribute to sustain the polarity and adhesion of RGCs,
      therefore affect production of RGCs and radial migration. Estrogen is a steroid
      hormone and contributes to the organizational sexual differentiation of the
      brain. We have previously demonstrated that ERbeta expression in the cerebral
      cortex during corticogenesis and contribute to cerebral cortex development. This
      has been further confirmed by studies from estrogen receptor beta knockout
      (ERbetaKO) mice, in which lack of ERbeta in mice induced abnormal development of
      cerebral cortical structure, retarded migration of the neurons, and abnormal
      morphology of RGCs with truncated or less organized radial processes. These
      indicate that estrogen via ERbeta affects RGCs development. Moreover, phenotype
      analysis in the ERbetaKO mice has confirmed that estrogen activation ERbeta
      influence the polarity of epithelial tissue and structure integrity by modulating
      the level of cadherins (E-cadherin and N-cadherin). Thus, we propose that ERbeta
      maybe affect the maintaining the polarity of RGCs through cadherins.

PMID- 21903334
TI  - Towards an extension of the two-variable model of carcinogenesis through
      oncogenes and tumour suppressor genes.
AB  - Currently, carcinogenesis is considered to be the result of mal-expression of
      tumour suppressor genes and oncogenes, leading either way to uncontrollable and
      disorganized cell mitosis. Recently a novel class of genes has drawn the interest
      of the scientific community. These are microRNAs (miRNAs), a class of noncoding
      RNAs, 20-23 nucleotides in length, that can up or downregulate gene expression of
      downstream gene targets (including transcription factors, oncogenes, and tumour
      suppressor genes) at the post-transcriptional level. Some members of this new
      class of genes seem to have the potential to act simultaneously either as
      oncogenes or as tumour suppressor genes depending on the molecular
      microenvironment of the cell. We elaborate on this hypothesis by giving examples
      of miRNAs (e.g. mir-9, miR-17-92) which seem to function by the abovementioned
      mechanism. This could mean that the deterministic notion of carcinogenesis as a
      result of merely tumour suppressor genes and oncogenes deregulation could be
      revised to contain the fact that certain members of this novel class of genes
      have the potential to play both roles simultaneously.

PMID- 21903335
TI  - Hexameric immunoglobulin M in humans: desired or unwanted?
AB  - Immunoglobulin M (IgM) is the first antibody produced upon infection, and is
      often suggested as the first line of defense of human immune system. In addition
      to being present on the surface of naive B cells as a monomeric molecule, IgM is
      always secreted as a polymer. The most abundant IgM polymer in humans is
      pentamer, composed of five monomeric units, joined together by so-called joining
      or J chain. On the other hand, it is well known that hexameric IgM can be also
      found in human sera. Its presence is often related to different dissorders
      (Waldenstrom's macroglobulinemia, cold agglutinin, and recurrent urinary
      bacterial infections), although it is believed that small amounts of hexamer are
      present in normal human sera as well. Unlike pentamer, IgM hexamer contains six
      monomeric blocks and completely lacks J chain. Although it has been decades since
      its discovery, the precise function of IgM hexamer is still unknown. Since it was
      documented that hexamer is very potent in activating complement, it is suggested
      that its production in humans must be under strict control, and that it is
      produced in special conditions, when strong activation of complement is
      absolutely needed. However, the question is whether hexameric IgM is really a
      secret weapon or just an undesirable molecule in humans. According to structural
      and known functional characteristics of both pentamers and hexamers of IgM, it
      can be concluded that hexamers are, in addition to being maybe too reactive to be
      around, probably not that efficient in protecting us from bacterial and viral
      infections.

PMID- 21903336
TI  - The application of digital surgical diagnosis and treatment technology: a
      promising strategy for surgical reconstruction of craniomaxillofacial defect and
      deformity.
AB  - The craniomaxillofacial defect and deformity always leads to serious dysfunction
      in mastication and facial contour damage, significantly reducing patients'
      quality of life. However, surgical reconstruction of a craniomaxillofacial hard
      tissue defect or deformity is extremely complex and often does not result in
      desired facial morphology. Improving the result for patients with
      craniomaxillofacial defect and deformity remains a challenge for surgeons. Using
      digital technology for surgical diagnosis and treatment may help solve this
      problem. Computer-assisted surgical technology and surgical navigation technology
      are included in the accurate digital diagnosis and treatment system we propose.
      These technologies will increase the accuracy of the design of the operation
      plan. In addition, the intraoperative real-time navigating location system
      controlling the robotic arm or advanced intelligent robot will provide accurate,
      individualized surgical treatment for patients. Here we propose the hypothesis
      that a digital surgical diagnosis and treatment technology may provide a new
      approach for precise surgical reconstruction of complicated craniomaxillofacial
      defect and deformity. Our hypothesis involves modern digital surgery, a three
      dimensional navigation surgery system and modern digital imaging technology, and
      our key aim is to establish a technological platform for customized digital
      surgical design and surgical navigation for craniomaxillofacial defect and
      deformity. If the hypothesis is proven practical, this novel therapeutic approach
      could improve the result of surgical reconstruction for craniomaxillofacial
      defect and deformity for many patients.

PMID- 21903337
TI  - Interaction between ionizing radiation and estrogen: what we are missing?
AB  - Following complexity as a new approach in science of 21st century biomonitoring
      of biological effects caused by ionizing radiation received an option of a new
      dimension. Insight in biological response of mammals to ionizing radiation
      exposure by integration of genome, non-genome and distant organ bystander effects
      will significantly change evaluation of health risk and preventive measures.
      Impact of estrogen on carcinogenesis caused by occupational or accidental
      exposure to ionizing radiation additionally enables biodosimetry to recognize
      vulnerable subpopulations according to gender and age. Estrogen, as a potent
      molecule involved in number of biological pathways during development and
      adulthood, shows close interaction with pathological processes launched by
      overexposure to ionizing radiation which should be included in future research
      and radiation protection.

PMID- 21903338
TI  - Mycobacterium paratuberculosis and autism: is this a trigger?
AB  - Autism is a heterogeneous group of life-long neurologic problems that begin in
      childhood. Success in efforts to understand and treat autism has been mostly
      elusive. The role of autoimmunity in autism has gained recognition both for
      associated systemic autoimmune disease and the presence of brain autoantibodies
      in autistic children and their family members. There is an acknowledged genetic
      susceptibility to autism--most notably allotypes of complement C4. C4 defects are
      associated with several autoimmune diseases and also confer susceptibility to
      mycobacterial infections. Mycobacterium avium ss. paratuberculosis (MAP) causes
      an enteric inflammatory disease in ruminant animals (Johne's disease) and is the
      putative cause of the very similar Crohn's disease in humans. Humans are widely
      exposed to MAP in food and water. MAP has been also linked to ulcerative colitis,
      irritable bowel syndrome, sarcoidosis, Blau syndrome, autoimmune (Type 1)
      diabetes, Hashimoto's thyroiditis and multiple sclerosis. Environmental agents
      are thought to trigger autism in the genetically at risk. Molecular mimicry is
      the proposed mechanism by which MAP is thought to trigger autoantibodies.
      Autoantibodies to brain myelin basic protein (MBP) is a common feature of autism.
      This article considers the subset of autoimmunity-related autism patients and
      postulates that MAP, through molecular mimicry to its heat shock protein HSP65,
      triggers autism by stimulating antibodies that cross react with myelin basic
      protein (MBP).

PMID- 21903339
TI  - What are candidate biobehavioral mechanisms underlying the association between
      secondhand smoke exposure and mental health?
AB  - There is a consistent positive and significant association between secondhand
      smoke exposure and mental health outcomes in the literature. There are potential
      genetic and behavioral confounders (e.g., psychological stress, maternal
      depression, and family functioning) were discussed, as well as potential causal
      neurobiological pathways (e.g., dopamine system). Further neurobiological
      research to establish causal pathways is needed as well as the integration of
      positive observational findings into clinical and public health prevention
      practices.

PMID- 21903340
TI  - A novel deployment design of vena cava filters might be the solution to their
      blockage problem.
AB  - The blockage of a vena cava filter (VCF) by the captured blood clots presents a
      serious problem to the patients. Commercially available cone-shaped VCFs such as
      the Gunther Tulip filter has an inherent structural flaw that leads the captured
      blood clots to be trapped in their front spire areas where the flow-induced shear
      stress is relatively low so that the clots cannot dissolve fast enough and will
      accumulate, gradually block the central passages of the filters. It is well known
      that for a Hagen-Poiseuille flow in a circular tube, the flow-induced shear
      stress is highest at the wall of the tube and lowest along its axis. Herein, we
      hypothesize that by reversely deploying a cone-shaped filter in the vena cava,
      the filter's blockage problem might be prevented. First of all, this kind of
      deployment scenario can force the captured blood clots to stay in the peripheral
      areas of the vena cava and keep the central passage of the filter unblocked.
      Secondly, this scenario can expose the captured blood clots to relatively high
      shear stress that may dissolve the clots faster.

PMID- 21903341
TI  - Hypoxia: the driving force of uterine myometrial stem cells differentiation into
      leiomyoma cells.
AB  - We propose that stem cells that display specific phenotypic and functional
      characteristics exist in human uterine myometrium. Under hypoxic circumstances,
      estrogen signaling pathways in certain myometrial stem cells are aberrantly
      activated, which leads to continuous differentiation of this portion of cells
      into leiomyoma cells. This process also protects the cells from undergoing
      physiological apoptotic or dedifferentiation. Therefore, we summarized some
      evidences for our bases and hypothesize that hypoxia may be the key contributor
      to the pathogenesis of leiomyoma through aberrant estrogen pathway activation of
      myometrial stem cells.

PMID- 21903342
TI  - Aging as a consequence of intracellular water volume and density.
AB  - Aging is the result of a gradual failure of physiological and/or biochemical
      pathways that culminates with the death of the organism. Until now, the causative
      factors of aging are elusive, despite the increasing number of theories that try
      to explain how aging initiates. Interestingly, aging cells show an increase in
      intracellular water volume, but this fact is barely explored in aging studies.
      All cells have a crowded cytoplasm, where the high concentration and proximity of
      macromolecules create an environment that excludes many small molecules,
      including water. In this crowded environment, water can be found in two states
      termed low density water (LDW), which shows low reactivity and has an ice-like
      structure, and high density water (HDW) that has a disorganized structure and is
      highly reactive. LDW predominates in a macromolecular crowded environment, while
      HDW is found only in microenvironments within cytoplasm. In this sense, we
      hypothesized that the failure in the water homeostasis mechanisms with time
      changes the equilibrium between LDW and HDW, increasing the concentration of
      intracellular HDW. Being reactive, HDW leads to the generation of reactive oxygen
      species and disturbs the crowded cytoplasm environment, resulting in a diminished
      efficiency of metabolic reactions. Noteworthy, the cell becomes less prone to
      repair damage when the concentration of HDW increases with time, resulting in
      aging and finally death. Interestingly, some biological mechanisms (e.g.,
      anhydrobiosis) reduce the concentration of intracellular water and prolong the
      life of cells and/or organisms. In this sense, anhydrobiosis and related
      biological mechanisms could be used as a platform to study new anti-aging
      therapies.

PMID- 21903343
TI  - Memory loss after electroconvulsive treatment--may the sudden alleviation of
      depression-inducing memories explain patient despair?
AB  - Electroconvulsive treatment (ECT) has developed over 70 years to a modern,
      effective way of lifting depressive moods. Memory loss after electroconvulsive
      treatment is the only remaining relevant criticism of the treatment modality when
      considering the overall rate of remission from this treatment compared to all
      other treatment modalities. A depressive state impedes memory. After treatment
      memory improves on several qualities of cognition. However, comparing a person's
      memory ability from the months before depression started to the level after a
      course of ECT is never done, of obvious reasons. There are great clinical
      difficulties explaining who would develop memory problems, regardless of
      stimulation techniques, age or sex of the patient. HYPOTHESES: The memory loss
      seen in some patients undergoing electroconvulsive treatment (ECT) is not
      explained by the treatment alone. After ECT unpleasant memories are disclosed
      rapidly and the patient may unconsciously try to defend herself by extending
      memory repression to other areas of memory. This may be unrelated to treatment
      modality, number of sessions or severity of depression. Psychological factors may
      partly explain why some patients unfold memory problems when the depression is
      rapidly lifted, rather than the treatment modality itself.

PMID- 21903344
TI  - A possible role for long non-coding RNA in modulating signaling pathways.
AB  - Signaling proteins often engage in multiple protein-protein interactions that are
      dependent upon cellular context. Little is known about how signaling proteins
      select their interacting targets. The Ras GTPase is an example of a protein that
      can activate a large number of distinct and interconnected downstream signaling
      pathways. Hyperactive forms of Ras are commonly found in a variety of different
      cancers, often due to somatic mutations within the RAS gene. Despite extensive
      studies to identify Ras-regulated pathways, it is still not known exactly which
      pathways might be activated by hyperactive Ras in a given cellular and disease
      context. Long non-coding RNAs (lncRNAs) are RNA transcripts longer than 200 bp
      exhibiting spatially and temporally-regulated expression patterns. LncRNAs have
      been shown to harbor biological activities but the functions of the great
      majority of lncRNAs are not known. We hypothesize that long non-coding RNAs serve
      as signaling modulators linking Ras and potentially other signaling proteins to
      their specific downstream targets and may therefore play a key role in how
      signals are propagated in a specific cellular environment. In support of our
      hypothesis we argue that lncRNAs have been shown to bind and regulate protein
      complexes targeting their enzymatic activity towards specific substrates. It has
      also been demonstrated that specific lncRNAs are expressed in particular types of
      cancers where they may influence tumor progression. Studies suggest that lncRNAs
      have evolved to help regulate complex biological processes that require the
      ability to stringently discriminate between a large number of potential
      effectors. If our hypothesis is correct, we envision that it will be possible to
      predict the target pathway of a mutant protein based on the lncRNA profile in a
      specific cancer. More generally, this will expand our understanding of how signal
      transduction networks are wired within a given biological context.

PMID- 21903345
TI  - Computer simulation of nerve transfer strategies for restoring shoulder function
      after adult C5 and C6 root avulsion injuries.
AB  - PURPOSE: Functional ability after nerve transfer for upper brachial plexus
      injuries relies on both the function and magnitude of force recovery of targeted
      muscles. Following nerve transfers targeting either the axillary nerve,
      suprascapular nerve, or both, it is unclear whether functional ability is
      restored in the face of limited muscle force recovery. METHODS: We used a
      computer model to simulate flexing the elbow while maintaining a functional
      shoulder posture for 3 nerve transfer scenarios. We assessed the minimum restored
      force capacity necessary to perform the task, the associated compensations by
      neighboring muscles, and the effect of altered muscle coordination on movement
      effort. RESULTS: The minimum force restored by the axillary, suprascapular, and
      combined nerve transfers that was required for the model to simulate the desired
      movement was 25%, 40%, and 15% of the unimpaired muscle force capacity,
      respectively. When the deltoid was paralyzed, the infraspinatus and subscapularis
      muscles generated higher shoulder abduction moments to compensate for deltoid
      weakness. For all scenarios, movement effort increased as restored force capacity
      decreased. CONCLUSIONS: Combined axillary and suprascapular nerve transfer
      required the least restored force capacity to perform the desired elbow flexion
      task, whereas single suprascapular nerve transfer required the most restored
      force capacity to perform the same task. Although compensation mechanisms allowed
      all scenarios to perform the desired movement despite weakened shoulder muscles,
      compensation increased movement effort. Dynamic simulations allowed independent
      evaluation of the effect of restored force capacity on functional outcome in a
      way that is not possible experimentally. CLINICAL RELEVANCE: Simultaneous nerve
      transfer to suprascapular and axillary nerves yields the best simulated
      biomechanical outcome for lower magnitudes of muscle force recovery in this
      computer model. Axillary nerve transfer performs nearly as well as the combined
      transfer, whereas suprascapular nerve transfer is more sensitive to the magnitude
      of reinnervation and is therefore avoided.

PMID- 21903346
TI  - Recent advances for the management of Raynaud phenomenon using botulinum
      neurotoxin A.

PMID- 21903348
TI  - Reservoirs of Staphylococcus aureus in meat sheep and dairy cattle.
AB  - The objective of the study was to investigate reservoirs and transmission of S.
      aureus in ewes and lambs in 3 meat sheep flocks. Repeated sampling of milk, teat
      skin, nasal- and vaginal mucous membranes was performed and samples were analysed
      for S. aureus. For comparison, samples were also collected from cows and young
      heifers in 3 dairy cattle herds. Selected isolates were compared by pulsed-field
      gel electrophoresis (PFGE). S. aureus was detected in 8 (1.5%) of 520 milk
      samples from ewes and in 38 (6.4%) of 588 milk samples from cows. From body site
      swabs, S. aureus was found in 394 (32.6%) of 1208 samples from sheep and in 67
      (16.0%) of 420 samples from cattle. The proportion of S. aureus-positive nasal
      swabs from ewes and cows were 56.7% and 13.9%, respectively. From lambs, 58.2% of
      the nasal swabs were S. aureus-positive. In each flock, one S. aureus pulsotype
      predominated. Identical S. aureus pulsotypes were found in milk and from body
      sites. Paired S. aureus isolates from the nasal cavity of (i) ewes and their
      lambs, (ii) twins and (iii) from repeated swabs of individual ewes were compared
      by PFGE, and in the majority of cases the two isolates were identical. The
      results contribute new knowledge indicating frequent transmission of S. aureus
      between the dam and her lambs and within animals in a flock. In contrast to
      cattle, S. aureus is frequently present in the nose of sheep which may represent
      the primary reservoir of S. aureus in sheep flocks.

PMID- 21903347
TI  - Four-year outcomes from the Early Re-Intervention (ERI) experiment using Recovery
      Management Checkups (RMCs).
AB  - BACKGROUND: While drug abuse is the 10th leading cause of mortality in the US,
      the public health care system has been slow to adopt a chronic disease approach
      with aggressively timed monitoring and interventions. Drug abuse remains isolated
      from adoption into the "chronic condition" model of care. This paper evaluates
      the efficacy of quarterly Recovery Management Checkups (RMCs) on treatment
      reentry and long-term substance use in the context of chronic substance use
      disorders. METHODS: 446 adult substance users were randomly assigned to RMC or a
      control group and assessed quarterly for 4 years (94% completion). The main
      outcome measures were: time from need of treatment to treatment reentry,
      frequency of treatment reentry, days of treatment, number of substance use
      related problems per month, and total days abstinent. RESULTS: Participants in
      the RMC condition were significantly more likely than participants in the control
      group to return to treatment sooner, to return at all, to return more times, and
      to receive more total days of treatment. They subsequently had significantly
      fewer quarters in need of treatment, fewer substance related problems per month,
      and more total days of abstinence. Effects were larger for those with earlier
      onset and higher crime/violence scores. CONCLUSIONS: RMC is an effective method
      of monitoring and re-intervening with chronic substance users and is associated
      with improved long-term outcomes. A subgroup of people for whom RMC did not
      appear to be "enough," signals a need to explore more intensive models to address
      chronicity.

PMID- 21903349
TI  - Bilateral sudden sensorineural hearing loss caused by alcohol abuse and heroin
      sniffing.
AB  - Objective. Acute or chronic heroin abuse has been associated with various central
      neurologic pathologies and, occasionally, with peripheral nervous system damage.
      The effect of heroin on hearing has not been adequately documented, although
      several cases with sudden hearing loss owed to heroin abuse have been reported.
      We present a young male with bilateral sudden sensorineural hearing loss,
      following heroin sniffing and alcohol consumption. Methods. Our patient underwent
      a detailed clinical and audiological evaluation, including auditory brainstem
      responses and otoacoustic emission. Routine laboratory blood tests and imaging
      studies were performed. Results. The patient was treated with corticosteroids and
      magnesium, resulting in complete restoration of hearing after one month.
      Conclusion. Sudden hearing loss owed to heroin abuse is usually curable,
      following adequate treatment.

PMID- 21903350
TI  - Acute supraglottitis in adults: what's the optimal airway intervention?
AB  - OBJECTIVES: To validate the Friedman stage and define the proper timing for
      airway intervention in adult cases of acute supraglottitis, we evaluated the
      clinical courses and management of adult patients. METHODS: 202 adult patients
      with acute supraglottitis were included in this study. The diagnosis of
      supraglottitis was established by flexible nasolaryngoscopic examination.
      Friedman stages were classified in each patient. In this study, the first three
      days of serial nasolaryngoscopic findings for each patient were evaluated.
      RESULTS: All patients were treated successfully with only conservative methods.
      There were no significant differences between patients with Friedman stages I or
      II/III. Among the patients that had serial nasolaryngoscopic findings, only one
      patient presented with progressive swelling of the epiglottis, and there were no
      cases of persistent swelling. CONCLUSION: The airway intervention threshold
      should be raised from Friedman stages II-III. And, airway intervention should not
      be needed if patients are tolerant of their respiratory discomfort.

PMID- 21903352
TI  - Hypertensive encephalopathy presenting as status epilepticus in a three year old.
AB  - BACKGROUND: Hypertensive encephalopathy is one of the few neurologic emergencies
      in which prompt diagnosis and treatment can prevent permanent neurological
      damage. This syndrome is rarely seen in children. OBJECTIVES: To discuss the
      recognition of hypertensive encephalopathy as a cause of acute neurological
      changes in children. CASE REPORT: We present the case of a 3-year-old boy who
      presented to the Emergency Department with seizures due to hypertensive
      encephalopathy. A review of the literature on the subject follows the case
      report. CONCLUSIONS: Hypertensive encephalopathy is a rare cause of acute
      neurological changes in children that can cause permanent damage if not
      recognized early. This case illustrates the importance of considering this
      syndrome as a potential cause of neurological symptoms, especially as
      neuroimaging can initially be misleading.

PMID- 21903353
TI  - Torsion of an undescended testis located in the inguinal canal.
AB  - BACKGROUND: Torsion of undescended testis located within the inguinal canal is a
      rare finding in the emergency department (ED). This diagnosis can present as
      undifferentiated abdominal or groin pain, and a full genitourinary examination is
      essential to making this diagnosis. OBJECTIVES: We present this case to increase
      awareness among emergency physicians regarding torsion of undescended testis.
      CASE REPORT: A 5-year-old boy presented to the ED with abdominal pain and a mass
      in his right groin. Physical examination and Doppler ultrasound were used to
      diagnose torsion of undescended testis. CONCLUSIONS: In a patient with
      undescended testis, torsion must be considered as a cause of abdominal or groin
      pain. Full genitourinary examination is essential to making this diagnosis.

PMID- 21903354
TI  - Subtle vaginal evisceration resulting in small bowel evisceration: a case report.
AB  - BACKGROUND: Evisceration of bowel contents through the vagina is a rare event
      that may be complicated by bowel obstruction. OBJECTIVE: We report a case of
      vaginal evisceration with small bowel obstruction which, in contrast to previous,
      more dramatic case reports in the literature, is a more subtle and, in fact,
      characteristic clinical presentation for this unusual occurrence. CASE REPORT: A
      72-year-old woman with a previous history of pelvic surgery presented to the
      Emergency Department with lower abdominal discomfort and a prolapsing mass from
      her vagina. She was initially discharged home after bedside reduction of the
      mass, but returned 48 h later with worsening symptoms. A computed tomography scan
      on her repeat visit confirmed evisceration of bowel into the vaginal vault with
      obstruction of distal bowel loops. Surgical and gynecologic services were
      consulted and the patient underwent partial small bowel resection and vaginal
      cuff repair in the operating room. CONCLUSION: Early recognition of subtle
      presentations of vaginal evisceration is crucial for preserving bowel viability
      and preventing morbidity from bowel ischemia or infarction. Risk factors for this
      rare condition include postmenopausal status, previous pelvic surgery, and
      presence of an enterocele.

PMID- 21903355
TI  - What perceptions do patients have of decision making (DM)? Toward an integrative
      patient-centered care model. A qualitative study using focus-group interviews.
AB  - OBJECTIVE: To understand patients' perceptions of decision making and identify
      relationships among decision-making models. METHODS: This qualitative study was
      made up of four focus group interviews (elderly persons, users of health support
      groups, students, and rural inhabitants). Participants were asked to report their
      perceptions of decision making in three written clinical scenarios (hypertension,
      breast cancer, prostate cancer). The analysis was based on the principles of
      grounded theory. RESULTS: Most patients perceived decision making as shared
      decision making, a deliberative question-response interaction with the physician
      that allowed patients to be experts in obtaining clearer information,
      participating in the care process, and negotiating compromises with physician
      preferences. Requesting second opinions allowed patients to maintain control,
      even within the paternalistic model preferred by elderly persons. Facilitating
      factors (trust, qualitative non-verbal communication, time to think) and
      obstacles (serious/emergency situations, perceived inadequate scientific
      competence, problems making requests, fear of knowing) were also part of shared
      decision making. CONCLUSION AND PRACTICE IMPLICATIONS: In the global concept of
      patient-centered care, shared decision making can be flexible and can integrate
      paternalistic and informative models. Physicians' expertise should be associated
      with biomedical and relational skills through listening to, informing, and
      advising patients, and by supporting patients' choices.

PMID- 21903356
TI  - Elevation of hemopexin-like fragment of matrix metalloproteinase-2 tissue levels
      inhibits ischemic wound healing and angiogenesis.
AB  - OBJECTIVE: Matrix metalloproteinase-2 (MMP-2) degrades type IV collagen and
      enables endothelial cell (EC) migration during angiogenesis and wound healing.
      Peroxisomal biogenesis factor 2 (PEX2), a by-product of activated MMP-2
      autocatalysis, competitively inhibits newly activated MMP-2 from EC surface
      binding and migration. We hypothesize that PEX2 is elevated during limb ischemia
      and contributes to poor wound healing, with decreased capillary density. METHODS:
      Western blot was used to identify PEX2 in the hind limbs of FVB/NJ mice with
      surgically induced ischemia. The PEX2 effect on healing was evaluated by
      calculating the area of exposed muscle after wounding the dorsum of mice and
      administering daily injections with human recombinant PEX2 (hrPEX2). Wounds were
      also injected with lentivirus-expressing PEX2 (PEX2-LV), harvested on
      postoperative day 7 and processed for staining. Epithelial gap was assessed with
      light microscopy. Capillary density was evaluated after wounding Tie2-green
      fluorescent protein (GFP)(+) transgenic FVB mice (ECs labeled green) and viral
      transduction with PEX2-LV. Wounds were harvested on postoperative day (POD) 7,
      frozen in liquid nitrogen, sectioned, and stained with Hoechst. Vessel density
      was assessed via fluorescence microscopy as the average number of capillaries/10
      high-powered fields. Paired t test was used to assess differences between the
      groups. RESULTS: PEX2 was elevated 5.5 +/- 2.0-fold (P = .005) on POD 2 and 2.9
      +/- 0.69-fold (P = .004) on POD 4 in gastrocnemius muscles of ischemic hind
      limbs. The wound surface area, or lack of granulation tissue and exposed muscle,
      decreased daily in all mice but was greater in the hrPEX2-treated mice by 12% to
      16% (P < .004). Wounds in the control group were completely covered with
      granulation tissue by POD 3. Wounds injected with hrPEX2 were not completely
      covered by POD 7 but continued to have exposed muscle. Microscopic examination of
      wounds after PEX2-LV viral transduction demonstrated an average epithelial gap of
      1.6 +/- 0.3 vs 0.64 +/- 0.3 MUm in control wounds (P < .04). Wounds from Tie2-GFP
      mice had an average number of 3.8 +/- 1.1 capillaries vs 6.9 +/- 1.2 in control
      wounds (P < .007). CONCLUSIONS: Our study links elevated PEX2 to ischemia and
      poor wound healing. We demonstrate comparative PEX2 elevation in ischemic murine
      hind limbs. Less granulation tissue is produced and healing is retarded in wounds
      subjected to hrPEX2 or viral transduction with PEX2-LV. Microscopic examination
      shows the wounds exhibit fewer capillaries, supporting the hypothesis that PEX2
      decreases angiogenesis.

PMID- 21903357
TI  - [Polysomnographic studies on sleep in adult borderline personality disorder].
AB  - BACKGROUND: Borderline personality disorder (BPD) represents 2% of the general
      population, 10% of outpatient psychiatry facilities, 20% of inpatients and nearly
      41% of patients seen in Emergency Room for attempted suicide. Also, 10% complete
      suicide and 64-66% have comorbid substance dependence. In addition, several
      studies report sleep subjective complaints in patients with BPD, and research has
      explored objective sleep disturbances. OBJECTIVE: To examine the results of
      previous studies in polysomnography in BPD to better characterize the objective
      sleep disturbances in this population. DATA SOURCES AND STUDY SELECTION: A review
      of the literature on MedLine and PsycINFO using the term "borderline personality
      disorder", "sleep" and "polysomnography" allowed the review of 15 original
      articles on sleep assessed by PSG in subjects adults with BPD, published between
      1980 and may 2010. RESULTS: Compared with healthy subjects, a decreased onset
      delay of rapid eye movements (REM) sleep and an increased REM density have been
      observed in BPD. In addition BPD shares with major depression the following
      disturbances: increase in onset latency, decreased total sleep time and
      efficiency. LIMITATIONS: Differences between studies regarding sex, age, mood
      state at the time of the study and psychiatric comorbidity influence the results,
      which explains the disparity in findings. CONCLUSION: There are objective
      disturbances associated with BPD according to polysomnographic studies.

PMID- 21903358
TI  - Gender differences in social anxiety disorder: results from the national
      epidemiologic sample on alcohol and related conditions.
AB  - This study examined gender differences among persons with lifetime social anxiety
      disorder (SAD). Data were derived from the National Epidemiologic Survey on
      Alcohol and Related Conditions (n=43,093), a survey of a representative community
      sample of the United States adult population. Diagnoses of psychiatric disorders
      were based on the Alcohol Use Disorder and Associated Disabilities Interview
      Schedule-DSM-IV Version. The lifetime prevalence of SAD was 4.20% for men and
      5.67% for women. Among respondents with lifetime SAD, women reported more
      lifetime social fears and internalizing disorders and were more likely to have
      received pharmacological treatment for SAD, whereas men were more likely to fear
      dating, have externalizing disorders, and use alcohol and illicit drugs to
      relieve symptoms of SAD. Recognizing these differences in clinical symptoms and
      treatment-seeking of men and women with SAD may be important for optimizing
      screening strategies and enhancing treatment efficacy for SAD.

PMID- 21903359
TI  - Identification of ETFB as a candidate protein that participates in the
      mechanoregulation of fibroblast cell number in collagen gel culture.
AB  - BACKGROUND: Fibroblast activation is strongly influenced by mechanical
      environment in the wound-healing process, especially in fibrosis. Mechanically
      stressed three-dimensional collagen embedded culture is a useful model
      representing fibroblasts in morphological as well as biochemical situations
      encountered during fibrosis. OBJECTIVE: To find key proteins involved in reducing
      the number of fibroblasts during mechanical stress, we performed two-dimensional
      gel electrophoresis (2DE)-based differential display and siRNA-based functional
      screening with collagen gel culture focusing on the differences between attached
      and detached culture environments. METHODS: Membrane extracts of fibroblasts from
      1 day of attached or detached cultures were subjected to 2DE. We compared protein
      expression levels and identified the attached-culture-dominant proteins by MALDI
      TOF-MS. Next, fibroblasts were transfected with siRNA and embedded in collagen
      gel. Cell number was counted after 3 days in culture. RESULTS: Eight attached
      culture dominant proteins were identified with MALDI-TOF-MS. Transfection of
      siRNA against these proteins demonstrated that electron transfer flavoprotein
      beta subunit (ETFB)-specific siRNA reduced the cell number in the attached
      culture without a decrease in the detached culture. CONCLUSION: ETFB participates
      in the mechanoregulation of fibroblast cell number in collagen gel culture.

PMID- 21903360
TI  - Qualification opinion of novel methodologies in the predementia stage of
      Alzheimer's disease: cerebro-spinal-fluid related biomarkers for drugs affecting
      amyloid burden--regulatory considerations by European Medicines Agency focusing
      in improving benefit/risk in regulatory trials.
AB  - The European Medicines Agency (EMA) in London is responsible for the Regulatory
      review of new medicinal products for Marketing Authorisation, through which
      pharmaceutical companies may obtain first Marketing Authorisation and subsequent
      Variations valid throughout the EU and EFTA. The qualification opinion of novel
      methodologies is a new procedure where applicants can obtain scientific advice on
      new methodologies for regulatory clinical trials of efficacy of new compounds. It
      will help benefit/risk assessment of the CHMP. The definition of prodromal AD is
      acceptable. The "Dubois Criteria" as criteria to define the population must be
      validated in full at the time of the submission of the dossiers. Including a
      positive CSF biomarker profile is considered predictive for the evaluation of the
      AD-dementia type. However, although high CSF tau and low CSF Abeta42 are
      predictive of Alzheimer's disease, the criterion "positive CSF tau/Abeta42 ratio"
      is not well defined. The qualification of biomarkers in the pre-dementia stage of
      Alzheimer's disease will allow better inclusion criteria of patients in pre
      dementia trials in which the benefit/risk is higher for treatment with these
      novel compounds.

PMID- 21903361
TI  - A mathematical formula for prediction of gray and white matter volume recovery in
      abstinent alcohol dependent individuals.
AB  - We propose a mathematical formula that predicts the trajectory of the recovery
      from lobar gray and white matter volume deficits in individuals with sustained
      abstinence from alcohol. The formula was validated by using MRI-measured
      volumetric data from 16 alcohol dependent individuals who had brain scans at
      three time points during abstinence from alcohol. Using the measured volumetric
      data of each individual from the first two time points, we estimated the
      individual's gray and white matter volume of the frontal, parietal and temporal
      lobes for the third time point using the formula. Similarly, using the measured
      data for the second and third time points, we estimated the first time point data
      for each individual. The data predicted from the formula were very similar to the
      experimentally measured data for all lobes and for both gray and white matter.
      The intra-class correlation coefficients between the measured data and the data
      estimated from the formula were >0.95 for almost all the tissues. The formula may
      also be applicable in other neuroimaging studies of tissue volume changes such as
      white matter myelination during brain development and white matter demyelination
      or brain volume loss in neurodegenerative diseases, such as Alzheimer's disease.

PMID- 21903363
TI  - [Vomiting newborn].

PMID- 21903364
TI  - [Michel Pierson's syndrome].

PMID- 21903365
TI  - [Neonatal cyanosis due to fetal hemoglobin M-Osaka].
AB  - The case of a newborn with isolated neonatal cyanosis on day 1 is reported. The
      basic investigations were sufficient to reach the diagnosis. A rare abnormal
      fetal hemoglobin was isolated. The prognosis of this disease is excellent and
      self-resolving.

PMID- 21903366
TI  - Consensus on: Screening and therapy of coronary heart disease in diabetic
      patients.
AB  - The screening and best treatment for coronary heart disease in diabetic patients
      is still a matter of debate. For this reason the main Italian scientific
      societies dealing with diabetes and cardiovascular diseases have tried to
      finalize a document providing shared recommendations based on the available
      evidence on : 1) how and who to screen for coronary heart disease, 2)
      methodologies for the characterization of existing coronary heart disease 3)
      evaluation of the optimal treatment of cardiovascular risk factors and 4)
      appropriate revascularization procedures. For each of these points, the levels of
      evidence and strength of recommendations used in the Italian Standard of Care
      were adopted.

PMID- 21903367
TI  - The preventive effects of dark chocolate on impaired endothelial function in
      medical personnel working sequential night shifts.

PMID- 21903368
TI  - Eurycomanone suppresses expression of lung cancer cell tumor markers, prohibitin,
      annexin 1 and endoplasmic reticulum protein 28.
AB  - Bioactive compounds from the medicinal plant, Eurycoma longifolia Jack have been
      shown to promote anti-proliferative effects on various cancer cell lines. Here we
      examined the effects of purified eurycomanone, a quassinoid found in Eurycoma
      longifolia Jack extract, on the expression of selected genes of the A549 lung
      cancer cells. Eurycomanone inhibited A549 lung cancer cell proliferation in a
      dose-dependent manner at concentrations ranging from 5 to 20 MUg/ml. The
      concentration that inhibited 50% of cell growth (GI(50)) was 5.1 MUg/ml. The anti
      proliferative effects were not fully reversible following the removal of
      eurycomanone, in which 30% of cell inhibition still remained (p<0.0001, T-test).
      At 8 MUg/ml (GI(70)), eurycomanone suppressed anchorage-independent growth of
      A549 cells by >25% (p<0.05, T-test, n=8) as determined using soft agar colony
      formation assay. Cisplatin, a chemotherapy drug used for the treatment of non
      small cell lung cancer on the other hand, inhibited A549 cells proliferation at
      concentrations ranging from 0.2 MUg/ml to 15 MUg/ml with a GI(50) of 0.58 MUg/ml.
      The treatment with eurycomanone reduced the abundance expression of the lung
      cancer markers, heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1, p53 tumor
      suppressor protein and other cancer-associated genes including prohibitin (PHB),
      annexin 1 (ANX1) and endoplasmic reticulum protein 28 (ERp28) but not the house
      keeping genes. The mRNA expressions of all genes with the exception of PHB were
      significantly downregulated, 72 h after treatment (p<0.05, T-test, n=9). These
      findings suggest that eurycomanone at viable therapeutic concentrations of 5-20
      MUg/ml exhibited significant anti-proliferative and anti-clonogenic cell growth
      effects on A549 lung cancer cells. The treatment also resulted in suppression of
      the lung cancer cell tumor markers and several known cancer cell growth
      associated genes.

PMID- 21903369
TI  - Differences in preterm and term milk fatty acid compositions may be caused by the
      different hormonal milieu of early parturition.
AB  - INTRODUCTION: The hormonal milieus of pregnancy and lactation are driving forces
      of nutrient fluxes supporting infant growth and development. The decrease of
      insulin sensitivity with compensatory hyperinsulinemia with advancing gestation,
      causes adipose tissue lipolysis and hepatic de novo lipogenesis (DNL). SUBJECTS
      AND METHODS: We compared fatty acid (FA) contents and FA-indices for enzyme
      activities between preterm (28-36 weeks) and term (37-42) milks, and between
      colostrum (2-5 days), transitional (6-15) and mature (16-56) milks. We
      interpreted FA differences between preterm and term milks, and their changes with
      lactation, in terms of the well known decrease of insulin sensitivity during
      gestation and its subsequent postpartum restoration, respectively. RESULTS:
      Compared with term colostrum, preterm colostrum contained higher indices of DNL
      in the breast (DNL-breast) and medium chain saturated-FA (MCSAFA), and lower DNL
      liver and monounsaturated-FA (MUFA). Preterm milk also had higher docosahexaenoic
      acid (DHA) in colostrum and transitional milk and higher arachidonic acid (AA) in
      mature milk. Most preterm-term differences vanished with advancing lactation. In
      both preterm and term milks, DNL-breast and MCSAFA increased with advancing
      lactation, while DNL-liver, MUFA, long chain SAFA and AA decreased. DHA decreased
      in term milk. MUFA was inversely related to MCSAFA in all samples, correlated
      inversely with PUFA in colostrum and transitional milks, but positively in mature
      milk. MCSAFA correlated inversely with PUFA in mature milk. CONCLUSION: Higher
      maternal insulin sensitivity at preterm birth may be the cause of lower MUFA (a
      proxy for DNL-liver) and higher MCSAFA (a proxy for DNL-breast) in preterm
      colostrum, compared with term colostrum. Restoring insulin sensitivity after
      delivery may be an important driving force for milk FA-changes in early
      lactation.

PMID- 21903370
TI  - Comparison of Symbicort(r) versus Pulmicort(r) on steroid pharmacodynamic markers
      in asthma patients.
AB  - BACKGROUND: Combination therapy with inhaled corticosteroids (ICS) and long
      acting beta(2)-adrenergic agonists (LABA) is reported to have superior effects on
      controlling asthma symptoms to ICS alone; however, there is no molecular-based
      evidence to explain the clinical effects. Here, the effect of the ICS/LABA
      combination was compared with ICS on glucocorticoid receptor (GR) activation in
      sputum macrophages. METHODS: In a randomised, double-blind cross-over placebo
      controlled 6-visit study, 10 patients with mild asthma were given placebo,
      formoterol (Oxis((r)) 12 MUg), budesonide (Pulmicort((r)) 200 MUg :BUD200, or 800
      MUg :BUD800), or budesonide/formoterol combination (Symbicort((r))) as a single
      100/6 MUg (SYM100) or double 200/12 MUg (SYM200) dose. Sputum macrophages were
      separated by plate adhesion from induced sputum. GR binding to the glucocorticoid
      response elements on oligonucleotides (GR-GRE binding) was evaluated by ELISA.
      mRNA expression of MAP-kinase phosphatase (MKP)-1 and IL-8 were measured by
      quantitative RT-PCR. RESULTS: GR-GRE binding was significantly increased after
      treatment with SYM100 (3.5 OD/10 MUg protein, median, p < 0.05) versus placebo
      (1.3) and BUD200 (1.6), and the induction was higher than that of BUD800 (2.4).
      MKP-1 mRNA was increased and IL-8 mRNA was significantly inhibited by BUD800,
      SYM100 and SYM200 versus placebo. CONCLUSIONS: The effects of SYM100 and SYM200
      on GR activation were not different from that of BUD800 and superior to BUD200.
      Thus, it has been confirmed at a molecular level that inhaled combination therapy
      with a lower dose of budesonide has an equivalent effect to a high dose of
      budesonide alone. In addition, GR-GRE binding is found to be a valuable
      pharmacodynamic marker for steroid efficacy in clinical studies.

PMID- 21903371
TI  - Small airway disease associated with Sjogren's syndrome: clinico-pathological
      correlations.
AB  - BACKGROUND: Relationships among clinical, physiological, imaging and pathological
      findings of small airway disease associated with Sjogren's syndrome have remained
      unclear. SUBJECTS AND METHODS: We retrospectively studied 14 patients who
      underwent surgical lung biopsy and who were diagnosed with small airway disease
      associated with primary or secondary Sjogren's syndrome. We compared clinical,
      bronchoalveolar lavage, physiological, imaging and pathological findings between
      primary and secondary Sjogren's syndrome. We scored HRCT and pathological
      abnormalities and investigated correlations among physiological, HRCT and
      pathological data, changes in physiological parameters and in HRCT scores after
      two years of treatment, as well as correlations between these values and
      pathological scores. RESULTS: Bronchoalveolar lavage fluid, physiological,
      imaging and pathological findings of the airways did not significantly differ
      between primary and secondary Sjogren's syndrome. Air trapping on HRCT negatively
      correlated with MEF50 and MEF25. Although lymphoid cell infiltration and
      peribronchiolar fibrosis were the most common pathologies, constrictive change
      scores correlated negatively with MEF50 and MEF25, positively with air trapping
      scores and negatively with improvements after therapy in MEF(50), MEF(25) and air
      trapping. CONCLUSIONS: Constrictive change was the most significant determinant
      of physiological and imaging presentations and of changes in these factors after
      therapy for small airway disease associated with Sjogren's syndrome.

PMID- 21903372
TI  - Narrating the social relations of initiating injecting drug use: transitions in
      self and society.
AB  - Few studies have explored drug injectors' accounts of their initiation of others
      into injecting. There also lacks research on the social relations of initiating
      injecting drug use in transitional society. We draw upon analyses of 42 audio
      recorded semi-structured interviews with current and recent injecting drug users,
      conducted in 2009 in the Republic of Moldova, a transitional society of south
      eastern Europe. A thematic analysis informed by narrative theory was undertaken,
      focusing on accounts of self-initiation and the initiation of others. We also
      reflect upon the potential of peer efforts to dissuade would-be injectors from
      initiating. Findings emphasise initiation into injecting as a symbolic identity
      transition, enabled through everyday social relations. In turn, our analysis
      locates the drug transitions of the self inside an account of societal
      transition. We find that personal narratives of self transition are made sense
      of, and presented, in relation to broader narratives of social transition and
      change. Furthermore, we explore how narratives of self-initiation, and especially
      the initiation of others, serve to negotiate initiation as a moral boundary
      crossing. Self-initiation is located inside an account of transitioning social
      values. In looking back, initiation is depicted as a feature of a historically
      situated aberration in normative values experienced by the 'transition
      generation'. Accounts of the initiation of others (which a third of our sample
      describe) seek to qualify the act as acceptable given the circumstances. These
      accounts also connect the contingency of agency with broader narratives of social
      condition. Lastly, the power of peers to dissuade others from initiating
      injection was doubted, in part because most self-initiations were accomplished as
      a product of agency enabled by environment as well as in the face of peer
      attempts to dissuade.

PMID- 21903373
TI  - Agricultural reuse of the digestate from low-cost tubular digesters in rural
      Andean communities.
AB  - This research aimed at assessing the properties of guinea pig manure digestate
      from low-cost tubular digesters for crops fertilization in rural Andean
      communities. To this end, field trials were carried out to evaluate the effect of
      the digestate on two common Andean crops: potato (Solanum tuberosum) and forage
      (Lolium multiflorum and Trifolium pratense L.). The potato yield (20-25 tha(-1))
      increased by 27.5% with digestate, by 15.1% with pre-compost and by 10.3% with
      the mixture, compared to the control. The forage yield (20-21 tha(-1)) increased
      by 1.4% with digestate - 50% dose, and by 8.8% with digestate - 100% dose and
      digestate - 150% dose, compared to the control. The results suggest that the
      digestate is an appropriate substitute of manure pre-compost for potato
      fertilization. The results with forage indicate that it can be applied in a range
      of doses, according to the amount produced by the digester. Currently, manure is
      either used for cooking or as fertilizer. With low-cost tubular digesters
      implementation, it could be used to feed the digester, using the digestate for
      crops fertilization and biogas for cooking; improving household living conditions
      and protecting the environment. Since soil properties in rural Andean communities
      differ from experimental layouts, the effect of fertilizers should be re
      evaluated in-situ in future research studies.

PMID- 21903374
TI  - Indirect measurements of field-scale hydraulic conductivity of waste from two
      landfill sites.
AB  - Management and prediction of the movement and distribution of fluids in large
      landfills is important for various reasons. Bioreactor landfill technology shows
      promise, but in arid or semi-arid regions, the natural content of landfilled
      waste may be low, thus requiring addition of significant volumes of water. In
      more humid locations, landfills can become saturated, flooding gas collection
      systems and causing sideslope leachate seeps or other undesirable occurrences.
      This paper compares results from two different approaches to monitoring water in
      waste. At the Brock West Landfill in eastern Canada, positive pore pressures were
      measured at various depths in saturated waste. The downward seepage flux through
      the waste is known, thus the vertical saturated hydraulic conductivity of the
      waste at this landfill was determined to be 3 * 10(-7)cm/s. By comparison, the
      Spadina Landfill in western Canada is predominantly unsaturated. The infiltration
      of moisture into the waste was measured using moisture sensors installed in
      boreholes which determined arrival time for moisture fronts resulting from major
      precipitation events as well as longer-term change in moisture content resulting
      from unsaturated drainage during winter when frozen ground prevented
      infiltration. The unsaturated hydraulic conductivity calculated from these data
      ranged from approximately 10(-6)cm/s for the slow winter drainage in the absence
      of significant recharge to 10(-2)cm/s or higher for shallow waste subject to high
      infiltration through apparent preferential pathways. These two very different
      approaches to field-scale measurements of vertical hydraulic conductivity provide
      insight into the nature of fluid movement in saturated and unsaturated waste
      masses. It is suggested that the principles of unsaturated seepage apply
      reasonably well for landfilled waste and that the hydraulic behavior of waste is
      profoundly influenced by the nature and size of voids and by the degree of
      saturation prevailing in the landfill.

PMID- 21903375
TI  - Silica nanoparticles based label-free aptamer hybridization for ATP detection
      using hoechst33258 as the signal reporter.
AB  - In this work, we have developed a simple and sensitive method for ATP detection
      using silica nanoparticles (NPs) as the platform and hoechst33258 as the signal
      reporter. The ATP-binding aptamers hybridize with the probe DNA (DNA(p))
      immobilized NPs to form the aptamer/DNA(p) duplex on the NPs surface. The
      conformational change of the aptamer leads to the decrease of the aptamer/DNA(p)
      duplex on the NPs due to the ATP-binding aptamer switches its structure from the
      aptamer/DNA(p) duplex to the aptamer/target complex in the presence of ATP. ATP
      detection can be easily realized by separating the silica nanoparticles and
      adding the hoechst33258 of intercalating to aptamer/DNA(p) (dsDNA). Good
      selectivity between ATP and CTP, GTP or UTP has been demonstrated, which is due
      to the specific recognition between ATP aptamer and ATP. The K(d) was estimated
      to be ~1mM from 0 to 4mM and a liner response was observed from 0 to 0.2mM with a
      detection limit of ~20MUM. Compared with other methods, the carboxyl-modified
      silica nanoparticles (~60nm) prepared by the reverse microemulsion method can
      serve as a stable and sensitive sensor platform because of their smaller size and
      facile conjugation with amine-containing molecules. In addition, the high
      sensitivity and selectivity of hoechst33258 was employed for the ssDNA and dsDNA
      determination, which takes advantage of the label-free aptamer and lower cost.

PMID- 21903376
TI  - Electrochemical synthesis of reduced graphene sheet-AuPd alloy nanoparticle
      composites for enzymatic biosensing.
AB  - A simple, fast, green and controllable approach was developed for electrochemical
      synthesis of a novel nanocomposite of electrochemically reduced graphene oxide
      (ERGO) and gold-palladium (1:1) bimetallic nanoparticles (AuPdNPs), without the
      aid of any reducing reagent. The electrochemical reduction efficiently removed
      oxygen-containing groups in ERGO, which was then modified with homogeneously
      dispersed AuPdNPs in a good size distribution. ERGO-AuPdNPs nanocomposite showed
      excellent biocompatibility, enhanced electron transfer kinetics and large
      electroactive surface area, and were highly sensitive and stable towards oxygen
      reduction. A biosensor was constructed by immobilizing glucose oxidase as a model
      enzyme on the nanocomposites for glucose detection through oxygen consumption
      during the enzymatic reaction. The biosensor had a detection limit of 6.9MUM, a
      linear range up to 3.5mM and a sensitivity of 266.6MUAmM(-1)cm(-2). It exhibited
      acceptable reproducibility and good accuracy with negligible interferences from
      common oxidizable interfering species. These characteristics make ERGO-AuPdNPs
      nanocomposite highly suitable for oxidase-based biosensing.

PMID- 21903377
TI  - Dual signal amplification for highly sensitive electrochemical detection of
      uropathogens via enzyme-based catalytic target recycling.
AB  - We report an ultrasensitive electrochemical approach for the detection of
      uropathogen sequence-specific DNA target. The sensing strategy involves a dual
      signal amplification process, which combines the signal enhancement by the
      enzymatic target recycling technique with the sensitivity improvement by the
      quantum dot (QD) layer-by-layer (LBL) assembled labels. The enzyme-based
      catalytic target DNA recycling process results in the use of each target DNA
      sequence for multiple times and leads to direct amplification of the analytical
      signal. Moreover, the LBL assembled QD labels can further enhance the sensitivity
      of the sensing system. The coupling of these two effective signal amplification
      strategies thus leads to low femtomolar (5fM) detection of the target DNA
      sequences. The proposed strategy also shows excellent discrimination between the
      target DNA and the single-base mismatch sequences. The advantageous intrinsic
      sequence-independent property of exonuclease III over other sequence-dependent
      enzymes makes our new dual signal amplification system a general sensing platform
      for monitoring ultralow level of various types of target DNA sequences.

PMID- 21903378
TI  - Essential oils from aromatic herbs as antimicrobial agents.
AB  - Bacterial resistance to multiple antibiotics is a health problem. Essential oils
      (EOs) possess antibacterial properties and have been screened as potential
      sources of novel antimicrobial compounds. Terpenes and terpenoids are components
      derived from EOs. Some of these EOs show inhibitory activity against
      Staphylococcus aureus. Carvacrol has specific effects on S. aureus and
      Staphylococcus epidermidis. Perilla oil suppresses expression of alpha-toxin,
      Staphylococcus enterotoxin A and B and toxic shock syndrome toxin. Geraniol shows
      good activity in modulating drug resistance in several gram-negative species. EOs
      could act as biopreservatives, reducing or eliminating pathogenic bacteria and
      increasing the overall quality of animal and vegetable food products. Although
      clinical studies are scarce, the uses of EOs for topical administration and as
      penetration enhancers for antiseptics are promising. Little information exists
      for oral administration.

PMID- 21903379
TI  - Antimicrobial properties of allium species.
AB  - The antimicrobial activity of Allium species has long been recognized, with
      allicin, other thiosulfinates, and their transformation products having
      antimicrobial activity. Alliums are inhibitory against all tested microorganisms
      such as bacteria, fungi, viruses, and parasites. Alliums inhibit multi-drug
      resistant microorganisms and often work synergistically with common
      antimicrobials. Allium-derived antimicrobial compounds inhibit microorganisms by
      reacting with the sulfhydryl (SH) groups of cellular proteins. It used to be
      thought that allicin reacts only with cysteine and not with non-SH amino acids,
      but evidence has accumulated that allicin and other thiosulfinates also react
      with non-SH amino acids.

PMID- 21903380
TI  - Cadmium and mercury removal from non-point source wastewater by a hybrid
      bioreactor.
AB  - The purpose of this study was to remove cadmium (Cd) and mercury (Hg) from non
      point source wastewater by a hybrid bioreactor consisting of two different
      processes (anaerobic-anoxic-aerobic and photoautotrophic). The results showed
      that the bioreactor could concurrently culture heterotrophic and autotrophic
      microorganisms, and removed Cd and Hg from the wastewater successfully. The
      average removal efficiencies were 79% and 66%, respectively for Cd and Hg. The
      relationship between Cd removal rate and biofilm mass was observed to be
      significant (p<0.05) during different seasons. The Hg removal was mainly due to
      the bioaccumulation in macrophytes via a photoautotrophic process. Due to the
      increase of the bacterial diversity under the rejuvenated conditions modulated by
      the hybrid bioreactor, the growth conditions of the native bacterial habitat were
      improved. The results demonstrate that the environmentally benign, easily
      deployed, sludge free and cost-effective hybrid bioreactor can efficiently remove
      Cd and Hg from non-point source wastewater.

PMID- 21903381
TI  - Biological pretreatment with a cellobiose dehydrogenase-deficient strain of
      Trametes versicolor enhances the biofuel potential of canola straw.
AB  - The use of Trametes versicolor as a biological pretreatment for canola straw was
      explored in the context of biofuel production. Specifically, the effects on the
      straw of a wild-type strain (52J) and a cellobiose dehydrogenase (CDH)-deficient
      strain (m4D) were investigated. The xylose and glucose contents of the straw
      treated with 52J were significantly reduced, while only the xylose content was
      reduced with m4D treatment. Lignin extractability was greatly improved with
      fungal treatments compared to untreated straw. Saccharification of the residue of
      the m4D-treated straw led to a significant increase in proportional glucose
      yield, which was partially attributed to the lack of cellulose catabolism by m4D.
      Overall, the results of this study indicate that CDH facilitates cellulose access
      by T. versicolor. Furthermore, treatment of lignocellulosic material with m4D
      offers improvements in lignin extractability and saccharification efficacy
      compared to untreated biomass without loss of substrate due to fungal catabolism.

PMID- 21903382
TI  - Production of lipases by solid state fermentation using vegetable oil-refining
      wastes.
AB  - Lipases were produced by a microbial consortium derived from a mixture of
      wastewater sludges in a medium containing solid industrial wastes rich in fats,
      under thermophilic conditions (temperature higher than 45 degrees C for 20 days)
      in 4.5-L reactors. The lipases were extracted from the solid medium using 100mM
      Tris-HCl, pH 8.0 and a cationic surfactant agent (cetyltrimethylammonium
      chloride). Different doses of surfactant and buffer were tested according to a
      full factorial experimental design. The extracted lipases were most active at 61
      65 degrees C and at pH 7.7-9. For the solid samples, the lipolytic activity
      reached up to 120,000 UA/g of dry matter. These values are considerably higher
      than those previously reported in literature for solid-state fermentation and
      highlight the possibility to work with the solid wastes as effective
      biocatalysts.

PMID- 21903383
TI  - Nitrogen conversion under rapid pyrolysis of two types of aquatic biomass and
      corresponding blends with coal.
AB  - Rapid pyrolysis of two types of aquatic biomass (blue-green algae and water
      hyacinth), and their blends with two coals (bituminous and anthracite) was
      carried out in a high-frequency furnace. Nitrogen conversions during rapid
      pyrolysis of the two biomass and the interactions between the biomass and coals
      on nitrogen conversions were investigated. Results show that little nitrogen
      retained in char after the biomass pyrolysis, and NH(3) yields were higher than
      HCN. During co-pyrolysis of biomass and coal, interactions between biomass and
      coal decreased char-N yields and increased volatile-N yields, but the total
      yields of NH(3)+HCN in volatile-N were decreased in which HCN formations were
      decreased consistently, while NH(3) formations were only decreased in the high
      temperature range but promoted in the low-temperature range. Interactions between
      blue-green algae and coals are stronger than those between water hyacinth and
      coal, and interactions between biomass and bituminous are stronger than those
      between biomass and anthracite.

PMID- 21903384
TI  - Pretreatment of corn stover using low-moisture anhydrous ammonia (LMAA) process.
AB  - A simple pretreatment method using anhydrous ammonia was developed to minimize
      water and ammonia inputs for cellulosic ethanol production, termed the low
      moisture anhydrous ammonia (LMAA) pretreatment. In this method, corn stover with
      30-70% moisture was contacted with anhydrous ammonia in a reactor under nearly
      ambient conditions. After the ammoniation step, biomass was subjected to a simple
      pretreatment step at moderate temperatures (40-120 degrees C) for 48-144 h.
      Pretreated biomass was saccharified and fermented without an additional washing
      step. With 3% glucan loading of LMAA-treated corn stover under best treatment
      conditions (0.1g-ammonia+1.0 g-water per g biomass, 80 degrees C, and 84 h),
      simultaneous saccharification and cofermentation test resulted in 24.9 g/l (89%
      of theoretical ethanol yield based on glucan+xylan in corn stover).

PMID- 21903386
TI  - Biomass production and fatty acid profile of a Scenedesmus rubescens-like
      microalga.
AB  - This investigation examined the effects of nitrogen-phosphate combined deficiency
      on the biomass yield, fatty acid methyl esters (FAME) production and composition
      from Scenedesmus rubescens-like microalga. A 15-day indoor culture was performed
      as a 3 * 3 factorial design (NaNO(3) levels: 3, 10 and 20mM; KH(2)PO(4) levels:
      20, 50 and 150 MUM). The algae grown under medium nitrogen concentration (10mM)
      and high phosphate concentration (150 MUM) reached the highest biomass (1223.5 +/
      152.5mg/L). Both nitrogen and phosphate had a significant influence on the FAME
      yield (P<0.05 and P<0.0001, respectively). The FAME yield from algae grown under
      low nitrogen (3mM) and phosphate concentration (20 MUM) increased throughout the
      experiment and the highest FAME yield (42.2 +/- 2.5% of AFDW) as well as C16 and
      C18 content (95.8 +/- 1.6% of AFDW) was achieved under these conditions. Algae
      grown under medium nitrogen concentration (10mM) and low phosphate concentration
      (20 MUM) had the highest FAME productivity (426.0mg/L +/- 135.0mg/L). Thus, the
      lower nitrogen concentration (3mM-10mM) and low phosphate concentration (20 MUM)
      would be an optimal combination tested to produce the most FAME from S. rubescens
      like algae.

PMID- 21903385
TI  - Surface carbohydrate analysis and bioethanol production of sugarcane bagasse
      pretreated with the white rot fungus, Ceriporiopsis subvermispora and microwave
      hydrothermolysis.
AB  - Effects of pretreatments with a white rot fungus, Ceriporiopsis subvermispora,
      and microwave hydrothermolysis of bagasse on enzymatic saccharification and
      fermentation were evaluated. The best sugar yield, 44.9 g per 100g of bagasse was
      obtained by fungal treatments followed by microwave hydrothermolysis at 180
      degrees C for 20 min. Fluorescent-labeled carbohydrate-binding modules which
      recognize crystalline cellulose (CjCBM3-GFP), non-crystalline cellulose (CjCBM28
      GFP) and xylan (CtCBM22-GFP) were applied to characterize the exposed
      polysaccharides. The microwave pretreatments with and without the fungal
      cultivation resulted in similar levels of cellulose exposure, but the combined
      treatment caused more defibration and thinning of the plant tissues. Simultaneous
      saccharification and fermentation of the pulp fractions obtained by microwave
      hydrothermolysis with and without fungal treatment, gave ethanol yields of 35.8%
      and 27.0%, respectively, based on the holocellulose content in the pulp. These
      results suggest that C. subvermispora pretreatment could be beneficial part of
      the process to produce ethanol from bagasse.

PMID- 21903387
TI  - Biological evaluation and docking studies of natural isocoumarins as inhibitors
      for human kallikrein 5 and 7.
AB  - Human kallikrein 5 and 7 (KLK5 and KLK7) are trypsin-like and chymotrypsin-like
      serine proteases, respectively, and promising targets for the treatment of skin
      desquamation, inflammation and cancer. In an effort to develop new inhibitors for
      these enzymes, we carried out enzymatic inhibition assays and docking studies
      with three isocoumarin compounds. Some promising inhibitors were uncovered, with
      vioxanthin and 8,8'-paepalantine being the most potent competitive inhibitors of
      KLK5 (K(i)=22.9 MUM) and KLK7 (K(i)=12.2 MUM), respectively. Our docking studies
      showed a good correlation with the experimental results, and revealed a distinct
      binding mode for the inhibitors at the binding sites of KLK5 and KLK7. In
      addition, the docking results suggested that the formation of hydrogen bonds at
      the oxyanion hole is essential for a good inhibitor.

PMID- 21903388
TI  - Cloning and characterization of a type III polyketide synthase from Aspergillus
      niger.
AB  - Type III polyketide synthases (PKSs) are the condensing enzymes that catalyze the
      formation of a myriad of aromatic polyketides in plant, bacteria, and fungi. Here
      we report the cloning and characterization of a putative type III PKS from
      Aspergillusniger, AnPKS. This enzyme catalyzes the synthesis of alkyl pyrones
      from C2 to C18 starter CoA thioesters with malonyl-CoA as an extender CoA through
      decaboxylative condensation and cyclization. It displays broad substrate
      specificity toward fatty acyl-CoA starters to yield triketide and tetraketide
      pyrones, with benzoyl-CoA as the most preferred starter. The optimal temperature
      and pH of AnPKS are 50 degrees C and 8, respectively. Under optimal conditions,
      the enzyme shows the highest catalytic efficiency (k(cat)/K(m)) of 7.4*10(5)s(
      1)M(-1) toward benzoyl-CoA. Homology modeling and site-directed mutagenesis were
      used to probe the molecular basis of its substrate specificity. This study should
      open doors for further engineering of AnPKS as a biocatalyst for synthesis of
      value-added polyketides.

PMID- 21903389
TI  - A compound isolated from Schisandra chinensis induces apoptosis.
AB  - Schizandra chinensis has been known to have five predominant tastes: salty,
      sweet, sour, astringent, and bitter. It has also been shown to have various
      effects on the cardiovascular system, gastrointestinal system, anti-inflammatory,
      central nervous system, endocrine system, and stress protect. However, its anti
      cancer activity on colon carcinoma HCT-116 cells has not been yet been examined.
      Thus, in this study, we attempted to isolate a compound from Schisandra chinensis
      that induced apoptosis in HCT-116 cells. An active compound was found and
      identified to be Gomisin A. It displayed apoptotic activity through caspase-7
      cleavage in colon carcinoma HCT-116 cells. In addition, we further assessed the
      effects of this compound using long-term survival clonogenic assay with HCT116
      cells.

PMID- 21903390
TI  - Discovery of GSK143, a highly potent, selective and orally efficacious spleen
      tyrosine kinase inhibitor.
AB  - The lead optimisation of the diaminopyrimidine carboxamide series of spleen
      tyrosine kinase inhibitors is described. The medicinal chemistry strategy was
      focused on optimising the human whole blood activity whilst achieving a
      sufficient margin over liability kinases and hERG activity. GSK143 is a potent
      and highly selective SYK inhibitor showing good efficacy in the rat Arthus model.

PMID- 21903391
TI  - Synthesis and biological activity of desmethoxy analogues of coruscanone A.
AB  - A series of simple desmethoxy analogues of coruscanone A was prepared via a novel
      version of Ti(iPrO)(4)-mediated Knoevenagel condensation of cyclopentenedione
      with substituted benzaldehydes and cinnamic aldehydes, and the compounds were
      evaluated for antifungal activity and cytotoxicity. The most potent 2
      benzylidenecyclopent-4-ene-1,3-dione possessed antifungal effect comparable to
      coruscanone A and a somewhat broader spectrum of activity against Candida
      species. The compound was also superior to fluconazole against several non
      albicans Candida sp. Evaluation of the ability of the compound to influence cell
      proliferation using two different assays showed that 2-benzylidenecyclopent-4-ene
      1,3-dione has lower cytotoxicity compared to the natural product.

PMID- 21903392
TI  - Synthesis and structure-activity relationships of novel substituted 8-amino, 8
      thio, and 1,8-pyrazole congeners of antitubercular rifamycin S and rifampin.
AB  - A series of rifamycin S and rifampin analogues incorporating substituted 8-amino,
      8-thio, and 1,8-pyrazole substituents has been synthesized. The compounds were
      made by activation of the C-8 phenol as a sulfonate ester, followed by
      displacement with selected nitrogen and sulfur nucleophiles. The analogues were
      screened in assays to quantify their antitubercular activity under both aerobic
      and anaerobic conditions, and for inhibition of wild-type Mycobacterium
      tuberculosis (MTB) RNAP and rifamycin-resistant MTB RNAP (S450L) via an in vitro
      rolling circle transcription assay. Additionally, the MIC(90) values were
      determined for these analogues against Escherichia coli strains. Although none of
      the analogues displayed superior enzymatic or microbiological activity to their
      parent scaffolds, the results are consistent with the Rif C-8 hydroxyl acting as
      a hydrogen bond acceptor with S450 and that Rif resistance in the S450L mutant is
      due to loss of this hydrogen bond. Representative analogues were also evaluated
      in the human pregnane X receptor (PXR) activation assay.

PMID- 21903393
TI  - Synthesis of glycoconjugate carbonic anhydrase inhibitors by ruthenium-catalysed
      azide-alkyne 1,3-dipolar cycloaddition.
AB  - Carbonic anhydrase IX (CA IX) is a recently validated target for the development
      of new cancer therapies. In this Letter we describe the synthesis and CA
      inhibition of a novel series of carbohydrate-based 1,5-disubstituted-1,2,3
      triazole benzenesulfonamides. The key step of our synthesis is the regioselective
      Huisgen's 1,3-dipolar cycloaddition reaction (1,3-DCR) from carbohydrate azide
      substrates and 4-ethynylbenzenesulfonamide using a ruthenium-catalysed azide
      alkyne cycloaddition (RuAAC). Our findings identified a number of triazole
      inhibitors (compounds 18, 19, 21-23, and 26) that block CA IX activity with
      inhibition constants less than 10 nM. One inhibitor (compound 17) possessed very
      good selectivity for CA IX over off-target CAs. These CA inhibitors have
      developmental potential to selectively target cancer cells, leading to cell
      death.

PMID- 21903394
TI  - Efficient synthesis of apricoxib, CS-706, a selective cyclooxygenase-2 inhibitor,
      and evaluation of inhibition of prostaglandin E2 production in inflammatory
      breast cancer cells.
AB  - An efficient synthesis of apricoxib (CS-706), a selective cyclooxygenase
      inhibitor, was developed using copper catalyzed homoallylic ketone formation from
      methyl 4-ethoxybenzoate followed by ozonolysis to an aldehyde, and condensation
      with sulfanilamide. This method provided multi-gram access of aprocoxib in good
      yield. Apricoxib exhibited potency equal to celecoxib at inhibition of
      prostaglandin E2 synthesis in two inflammatory breast cancer cell lines.

PMID- 21903395
TI  - Walking speed, unilateral leg loading, and step symmetry in young adults.
AB  - The purpose of this study was to examine the effects of gait speed and unilateral
      lower limb loading on step time and step length symmetry in healthy adults.
      Spatiotemporal gait data were collected from 22 healthy subjects (11 men, 11
      women), using the GaitRite walkway, under four randomly sequenced test
      conditions: self-selected speed (SS), fast speed (F), self-selected speed with
      the right leg loaded (LSS), and the fastest attainable speed with the right leg
      loaded (LF). The symmetry index, calculated with the formula [((R-L)/0.5 * (R+L))
      * 100], was used to quantify step time and step length symmetry. It was found
      that over-ground gait speed had no significant effects on the symmetry of step
      time or step length. Unilateral lower limb loading significantly increased step
      time asymmetry, with longer step time for the loaded leg. Step symmetry was
      further compromised and became more asymmetrical when, in addition to unilateral
      leg loading, subjects maximized their gait speed. This effect of fast speed with
      unilateral leg loading was particularly prominent in relation to step length,
      with its shortening in the unloaded leg and lengthening in the loaded leg. These
      observations in healthy subjects may serve as a reference for the assessment of
      gait symmetry in patients with unilateral lower limb pathologies.

PMID- 21903396
TI  - Contralateral hip and knee gait biomechanics are unchanged by total hip
      replacement for unilateral hip osteoarthritis.
AB  - Both the hip and knee contralateral to a total hip replacement (THR) have an
      increased risk of osteoarthritis (OA) progression, and ultimate joint
      replacement. It is also known that abnormal gait contributes to OA progression.
      For these reasons, we conducted a longitudinal analysis of contralateral hip and
      knee gait during the first year after unilateral THR to determine whether
      abnormal contralateral gait biomechanics emerge after THR. We analyzed the
      sagittal plane dynamic range of motion and 3D peak external moments from the
      asymptomatic hip and knee contralateral to a THR in a group of 26 subjects,
      evaluated preoperatively, and 3, 12, 24, and 52 weeks after THR, and a group of
      control subjects. We used t-tests and repeated measures ANOVA to test the
      hypotheses that contralateral hip and knee gait parameters are normal
      preoperatively, but change after THR. Preoperatively, the contralateral hip
      abduction moment and the contralateral knee adduction, flexion, and external
      rotation moments were significantly higher than normal in the THR group (p <=
      0.048). Apart from the peak hip extension moment, which decreased three weeks
      after surgery but returned to its preoperative value thereafter, there were no
      longitudinal changes during the study period (p >= 0.141). Preoperative gait
      abnormalities persisted postoperatively. Notably, the contralateral knee
      adduction moment was 32% higher than normal in the THR group. These results
      indicate a biomechanical basis for the increased contralateral OA risk after
      unilateral THR, and suggest that some patients may benefit from strategies to
      reduce loading on the contralateral limb.

PMID- 21903398
TI  - Exploiting differences in caspase-2 and -3 S2 subsites for selectivity: structure
      based design, solid-phase synthesis and in vitro activity of novel substrate
      based caspase-2 inhibitors.
AB  - Several caspases have been implicated in the pathogenesis of Huntington's disease
      (HD); however, existing caspase inhibitors lack the selectivity required to
      investigate the specific involvement of individual caspases in the neuronal cell
      death associated with HD. In order to explore the potential role played by
      caspase-2, the potent but non-selective canonical Ac-VDVAD-CHO caspase-2
      inhibitor 1 was rationally modified at the P(2) residue in an attempt to decrease
      its activity against caspase-3. With the aid of structural information on the
      caspase-2, and -3 active sites and molecular modeling, a 3-(S)-substituted-l
      proline along with four additional scaffold variants were selected as P(2)
      elements for their predicted ability to clash sterically with a residue of the
      caspase-3 S(2) pocket. These elements were then incorporated by solid-phase
      synthesis into pentapeptide aldehydes 33a-v. Proline-based compound 33h bearing a
      bulky 3-(S)-substituent displayed advantageous characteristics in biochemical and
      cellular assays with 20- to 60-fold increased selectivity for caspase-2 and ~200
      fold decreased caspase-3 potency compared to the reference inhibitor 1. Further
      optimization of this prototype compound may lead to the discovery of valuable
      pharmacological tools for the study of caspase-2 mediated cell death,
      particularly as it relates to HD.

PMID- 21903397
TI  - A brief survey of mRNA surveillance.
AB  - Defective mRNAs are degraded more rapidly than normal mRNAs in a process called
      mRNA surveillance. Eukaryotic cells use a variety of mechanisms to detect
      aberrations in mRNAs and a variety of enzymes to preferentially degrade them.
      Recent advances in the field of RNA surveillance have provided new information
      regarding how cells determine which mRNA species should be subject to destruction
      and novel mechanisms by which a cell tags an mRNA once such a decision has been
      reached. In this review, we highlight recent progress in our understanding of
      these processes.

PMID- 21903399
TI  - Inhibitory effect of novel 5-O-acyl juglones on mammalian DNA polymerase
      activity, cancer cell growth and inflammatory response.
AB  - We previously found that vitamin K(3) (menadione, 2-methyl-1,4-naphthoquinone)
      inhibits the activity of human mitochondrial DNA polymerase gamma (pol gamma). In
      this study, we focused on juglone (5-hydroxy-1,4-naphthoquinone), which is a 1,4
      naphthoquinone derivative, and chemically synthesized novel juglones conjugated
      with C2:0 to C22:6 fatty acid (5-O-acyl juglones). The chemically modified
      juglones enhanced mammalian pol inhibition and their cytotoxic and anti
      inflammatory activities. The juglone conjugated with oleic acid (C18:1-acyl
      juglone) showed the strongest inhibition of DNA replicative pol alpha activity
      and human colon carcinoma (HCT116) cell growth in 10 synthesized 5-O-acyl
      juglones. C12:0-Acyl juglone was the strongest inhibitor of DNA repair-related
      pol lambda, as well as the strongest suppression of the production of tumor
      necrosis factor (TNF)-alpha production induced by lipopolysaccharide (LPS) in the
      compounds tested. Moreover, this compound caused the greatest reduction in 12-O
      tetradecanoylphorbol-13-acetate (TPA)-induced acute inflammation in mouse ears.
      C12:0- and C18:1-Acyl juglones selectively inhibited the activities of mammalian
      pol species, but did not influence the activities of other pols and DNA metabolic
      enzymes tested. These data indicate that the novel 5-O-acyl juglones target anti
      cancer and/or anti-inflammatory agents based on mammalian pol inhibition.
      Moreover, the results suggest that acylation of juglone is an effective chemical
      modification to improve the anti-cancer and anti-inflammation of vitamin K(3)
      derivatives, such as juglone.

PMID- 21903400
TI  - Evaluation of PI polyamide conjugates with eight-base pair recognition and
      improvement of the aqueous solubility by PEGylation.
AB  - To investigate the effect of elongating base-pair (bp) recognition sequences, we
      synthesized N-methylpyrrole-N-methylimidazole (PI) polyamide conjugates with
      eight-bp recognition (3-5). The DNA alkylating activities of conjugates 3-5 were
      evaluated by high-resolution denaturing polyacrylamide gel electrophoresis with a
      208-bp DNA fragment. Conjugates 3-5 showed high alkylating activities at
      nanomolar concentrations. We then addressed the following issue about PI
      conjugates. Generally, PI polyamide conjugates hardly dissolve in aqueous
      solution. To improve the aqueous solubility, by the introduction of hydrophilic
      groups, we synthesized PI polyamide conjugates that were modified with a seco-CBI
      moiety (6-11). Conjugates 9-11 that were modified by methoxypolyethylene glycol
      (PEG) 750 acquired moderate solubility and stability in aqueous solution. In
      addition, conjugates 10 and 11 had high cytotoxicity against A549 and DU145.

PMID- 21903401
TI  - 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents.
AB  - Non-nucleoside reverse transcriptase inhibitors (NNRTI) are key components in
      highly active antiretroviral therapy for treating HIV-1. Herein we present the
      synthesis for a series of N1-alkylated uracil derivatives bearing omega-(2-benzyl
      and 2-benzoylphenoxy)alkyl substituents as novel NNRTIs. These compounds
      displayed anti-HIV activity similar to that of nevirapine and several of them
      exhibited activity against the K103N/Y181C RT mutant HIV-1 strain. Further
      evaluation revealed that the inhibitors were active against most nevirapine
      resistant mono- and di-substituted RTs with the exception of the V106A RT. Thus,
      the candidate compounds can be regarded as potential lead compounds against the
      wild-type virus and drug-resistant forms.

PMID- 21903403
TI  - Antifungal activity of a series of 1,2-benzisothiazol-3(2H)-one derivatives.
AB  - A series of broad-spectrum antifungal agents based on the 1,2-benzisothiazol
      3(2H)-one scaffold is reported. Preliminary structure-activity relationship
      studies have established the importance of the presence of the heterocyclic ring,
      a methyl group, and a phenyl ring for optimal manifestation of antifungal
      activity.

PMID- 21903402
TI  - Identification of novel small molecule inhibitors of 4-diphosphocytidyl-2-C
      methyl-D-erythritol (CDP-ME) kinase of Gram-negative bacteria.
AB  - The biosyntheses of isoprenoids is essential for the survival in all living
      organisms, and requires one of the two biochemical pathways: (a) Mevalonate (MVA)
      Pathway or (b) Methylerythritol Phosphate (MEP) Pathway. The latter pathway,
      which is used by all Gram-negative bacteria, some Gram-positive bacteria and a
      few apicomplexan protozoa, provides an attractive target for the development of
      new antimicrobials because of its absence in humans. In this report, we describe
      two different approaches that we used to identify novel small molecule inhibitors
      of Escherichia coli and Yersinia pestis 4-diphosphocytidyl-2-C-methyl D
      erythritol (CDP-ME) kinases, key enzymes of the MEP pathway encoded by the E.
      coli ispE and Y. pestisipk genes, respectively. In the first approach, we
      explored existing inhibitors of the GHMP kinases while in the second approach; we
      performed computational high-throughput screening of compound libraries by
      targeting the CDP-ME binding site of the two bacterial enzymes. From the first
      approach, we identified two compounds with 6-(benzylthio)-2-(2-hydroxyphenyl)-4
      oxo-3,4-dihydro-2H-1,3-thiazine-5-carbonitrile and (Z)-3-methyl-4-((5-phenylfuran
      2-yl)methylene)isoxazol-5(4H)-one scaffolds which inhibited E. coli CDP-ME kinase
      in vitro. We then performed substructure search and docking experiments based on
      these two scaffolds and identified twenty three analogs for structure-activity
      relationship (SAR) studies. Three new compounds from the isoxazol-5(4H)-one
      series have shown inhibitory activities against E. coli and Y. pestis CDP-ME
      kinases with the IC(50) values ranging from 7 to 13 MUM. The second approach by
      computational high-throughput screening (HTS) of two million drug-like compounds
      yielded two compounds with benzenesulfonamide and acetamide moieties which, at a
      concentration of 20 MUM, inhibited 80% and 65%, respectively, of control CDP-ME
      kinase activity.

PMID- 21903404
TI  - Probing DNA interstrand cross-link formation by an oxidized abasic site using
      nonnative nucleotides.
AB  - The C4'-oxidized abasic site (C4-AP) forms two types of interstrand cross-links
      with the adjacent nucleotides in DNA. Previous experiments revealed that dG does
      not react with the lesion and that formation of one type of cross-link is
      catalyzed by the opposing dA. iso-Guanosine.dC and 2-aminopurine.dT base pairs
      were used to determine why dG does not cross-link with C4-AP despite its well
      known reactivity with other bis-electrophiles. 7-Deaza-2'-deoxyadenosine was used
      to probe the role of the nucleotide opposite C4-AP in the catalysis of
      interstrand cross-link formation.

PMID- 21903405
TI  - Stem cell toxicity?

PMID- 21903406
TI  - Increasing donor-recipient weight mismatch in pediatric orthotopic heart
      transplantation does not adversely affect outcome.
AB  - OBJECTIVE: The aim of the study was to show the effect of heart transplant donor
      recipient weight mismatch on mortality, right-ventricular (RV) failure, and
      medium-term control of systemic blood pressure. METHODS: From 2000 to 2008
      inclusive, 161 patients undergoing orthotopic heart transplantation at our unit
      were retrospectively analyzed. The cohort was divided into three groups of
      similar size depending on the tertile ranges of the donor-recipient weight ratio.
      Median follow-up was 4.81 years. Donor-recipient body weight ratio was analyzed
      with respect to intubation time, time in intensive care unit (ITU), development
      of RV failure, medium-term survival, and freedom from medium-term hypertension.
      RESULTS: The median age was 115 months (23 days to 18 years), at a median weight
      of 26.9 kg (3-88 kg) at transplant. Median donor-recipient weight ratio was 1.61
      (0.62-3.25). Mean intubation time was 448 h (SD 749.2), mean time in the ITU
      302.7 h (SD 617.8). On linear regression, these were not related to donor
      recipient weight ratio. A total of 38 patients (23.6%) developed postoperative RV
      failure. Nearly one-fifth (18.9) of patients in the lowest tertile group
      developed RV failure. In the middle tertile group, 24.5% developed RV failure and
      28.8% in the upper tertile of weight mismatch, although this was not
      statistically significant (p = 0.48). On survival analysis, there was a higher
      mortality among those with the lowest tertile of mismatch (log-rank p = 0.04),
      but there was no difference in midterm survival on condition of survival to
      discharge (log-rank p = 0.14). There was also no association between weight ratio
      and freedom from medium-term hypertension as measured on serial 24-h ambulatory
      blood pressure monitoring (log-rank p = 0.39). There were nine patients in whom
      the weight mismatch was 3 or greater. There was no association between this
      'extreme' mismatch group and either midterm mortality (p = 0.76) or freedom from
      hypertension (p = 0.62), but this was associated with the need for postoperative
      extracorporeal membrane oxygenator (ECMO) support (p < 0.01). CONCLUSIONS: Our
      current policy involves accepting a maximum donor-recipient weight ratio of 3.
      These encouraging findings cautiously justify this policy, in an era when
      marginal donors are increasingly sought.

PMID- 21903408
TI  - Editorial comment Classification of aortic dissection: back to the future?

PMID- 21903409
TI  - Editorial comment: A tiny light in the darkness of pediatric myocardial
      protection and cardiopulmonary bypass!

PMID- 21903410
TI  - Early removal of chest tubes after lung resection---VATS the reason?

PMID- 21903411
TI  - Endovascular and thoracoscopic treatment for post-lobectomy hemothorax.

PMID- 21903412
TI  - Adaptive growth and remodeling of transplanted hearts in children.
AB  - OBJECTIVE: We aimed to evaluate the adaptive growth and remodeling behavior of
      the transplanted heart in pediatric heart-transplant recipients by comparing
      donor body surface area (BSA) and cardiac dimensions during transplantation with
      the corresponding parameters of the recipient over a period of time. METHODS: A
      retrospective review of medical and echocardiographic records of 167 children
      (8.65 +/- 5.98, median 9; range 0-17 years) who underwent orthotopic heart
      transplantation between 1987 and March 2010 was done. RESULTS: In the first 30
      days post-transplantation, right- and left-ventricular end-diastolic diameters,
      volumes, and myocardial mass were found to be significantly increased (z score
      3.96, p < 0.000) in relation to the recipients' BSA. Within the first year of
      post-transplantation, there was a significant reduction in the right-ventricular
      diameter (z score, -1.0 to +1.6, p = 0.000), left-ventricular diameter (z score 
      1.0 to +1.9, p = 0.000), right-ventricular end-diastolic volume (z score -1.3 to
      +1.9, p = 0.000) and left-ventricular end-diastolic volume (z score -1.3 to +1.8,
      p = 0.000), right-ventricular mass (z score, -1.4 to +1.7, p = 0.000) and left
      ventricular mass (z score, -1.4 to +1.8, p = 0.000). During subsequent follow-up
      periods of 2-5 and 6-10 years, the aforementioned cardiac dimensions and volumes
      increased appropriately in accordance to the BSA (p = 0.000). In all the cardiac
      dimensions and volumes measured, donor-recipient mismatch did not influence the
      continuous growth of the measured parameters, which was in accordance to the
      recipients' BSA over time. Kaplan-Meier survival analysis showed a survival rate
      of 61.7% at 10 years. There is no statistically significant difference in
      survival rate among patients with varying donor-recipient weight ratios and donor
      recipient BSA ratios (p = 0.53). CONCLUSIONS: This study demonstrates that the
      transplanted heart undergoes remodeling processes and grows adaptively, in
      accordance to the BSA, over a period of time.

PMID- 21903413
TI  - Nilotinib as frontline and second-line therapy in chronic myeloid leukemia: open
      questions.
AB  - Nilotinib is a second generation ABL tyrosine kinase inhibitor (TKI) that exerts
      major anti-leukemic effects in newly diagnosed patients with chronic myeloid
      leukemia (CML) as well as in most patients with imatinib-resistant CML. In
      freshly diagnosed patients, the anti-leukemic activity of nilotinib exceeds the
      efficacy of imatinib, and although long-term data for nilotinib are not available
      yet, the drug has recently been approved for firstline treatment of chronic phase
      CML in various countries. Still however, several questions concerning the optimal
      dose, follow-up parameters, long-term safety, and patient selection remain open.
      Likewise, it remains uncertain whether both Sokal low-risk and high-risk patients
      should receive nilotinib as frontline therapy in the future. Another question is
      whether nilotinib can completely eradicate CML in a subset of patients.
      Furthermore, it remains unclear whether and what comorbidity must be regarded as
      relative or absolute contra-indication for this TKI. To discuss these issues, the
      Austrian CML Working Group organized a series of meetings in 2010. In the current
      article, the outcomes from these discussions are summarized and presented
      together with recommendations for frontline use of TKIs in various groups of
      patients with CML. These recommendations should assist in daily practice as well
      as in the preparation and conduct of clinical trials.

PMID- 21903414
TI  - A method for following patients with retrievable inferior vena cava filters:
      results and lessons learned from the first 1,100 patients.
AB  - PURPOSE: Patients who have undergone implantation of a retrievable inferior vena
      cava (IVC) filter require continued follow-up to have the device removed when
      clinically appropriate and in a timely fashion to avoid potential long-term
      filter-related complications. The efficacy of a method for patient follow-up was
      evaluated based on a retrospective review of a single-institutional retrievable
      IVC filter experience. MATERIALS AND METHODS: Patients with retrievable IVC
      filters were tracked via a prospectively collected database designed specifically
      for patient follow-up. Follow-up consisted of periodic review of the electronic
      medical record. Patients were contacted by mail (at regular intervals one or more
      times) when removal of the filter was deemed appropriate. A retrospective review
      of the ultimate fate of the first 1,127 retrievable IVC filters placed at a
      single institution was performed. Retrieval rates were compared with those seen
      in the initial experience, during which no structured follow-up was performed.
      RESULTS: Of 1,127 filters placed, 658 (58.4%) were removed. Filter removal or
      declaration of the device as permanent was achieved in 860 patients (76.3%).
      Filter removal, declaration of the device as permanent, or establishment of the
      need for continued follow-up was achieved in 941 patients (83.5%). Only 186
      patients (16.5%) were lost to follow-up. CONCLUSIONS: The follow-up method
      described in the present study resulted in a statistically significant difference
      (P < .001) in the likelihood of a patient returning for IVC filter removal
      compared with a lack of follow-up (59% vs 24%).

PMID- 21903415
TI  - Correlation between severity of carotid stenosis and vascular reserve measured by
      acetazolamide brain perfusion single photon emission computed tomography.
AB  - Few studies have investigated the relationship between the degree of stenosis of
      the internal carotid artery (ICA) and cerebrovascular reserve (CVR). This study
      examined that relationship. A total of 56 ICAs in 43 patients were included.
      Computed tomography scan or magnetic resonance imaging showed no evidence of
      infarction in any of these patients. Both iodine-123-N-isopropyl-p
      iodoamphetamine ((123)IMP)-single photon emission computed tomography (SPECT) in
      the resting state and (123)IMP-SPECT with acetazolamide (ACZ) enhancement were
      performed. Quantitated cerebral blood flow (CBF) images were acquired with the
      (123)IMP autoradiography technique. The mean CBF without ACZ administration
      (resting CBF) and CVR in the middle cerebral artery territory were calculated
      using stereotactic extraction estimation (SEE) analysis software. The degree of
      stenosis in the origin of the ICA was calculated from intra-arterial digital
      subtraction angiography. Resting CBF was not correlated with the degree of ICA
      stenosis; however, nonlinear regression analysis (second-order equation) showed a
      moderate correlation between CVR and the degree of ICA stenosis. In 72% of the
      cases with a CVR <30%, ICA stenosis was >74%. Using the SEE method, CVR was
      moderately correlated with the degree of ICA stenosis. Our findings indicate that
      evaluating CVR by ACZ-enhanced (123)IMP-SPECT in patients with ICA stenosis is of
      clinical value.

PMID- 21903417
TI  - Cerebral infarction in a young man using high-dose anabolic steroids.
AB  - Anabolic androgenic steroid (AAS) abuse has increased among athletes in recent
      years. However, AAS abuse can increase hypercoagulopathy and cause
      cerebrovascular disease. We report a case of a 27-year-old man who had right
      hemiparalysis, hemianopia, dysarthria, and double vision in the middle of muscle
      training. He suspected acute disseminated encephalomyelitis at first, because of
      a preceding respiratory infection. However, extensive work-up was performed,
      including brain magnetic resonance imaging, transcranial Doppler and
      transesophageal echocardiography, confirming the final diagnosis of cardioembolic
      stroke. Physicians should be aware that cerebrovascular disease may be a side
      effect of AAS, even in younger populations.

PMID- 21903416
TI  - Successful amelioration of tinnitus in a stroke patient by low-dose gabapentin.
AB  - Bilaterally progressive tinnitus and hearing impairment occurred in a
      hypertensive patient shortly after an episode of right ganglionic hemorrhage.
      Audiometric tests showed a mixed sensorineural and conduction hearing loss. When
      low-dose gabapentin was administrated for the pre-existing postherpetic thoracic
      neuralgia, the tinnitus dramatically improved but recurred after discontinuation
      of the drug. Hearing function did not change. In view of a controversy of
      gabapentin and tinnitus in previous trials, the findings in this patient support
      that low-dose gabapentin benefits the subgroup of tinnitus patients with
      secondary contributing factors, such as stroke.

PMID- 21903418
TI  - Demographic, clinical, and radiologic predictors of neurologic deterioration in
      patients with acute ischemic stroke.
AB  - One-third of patients with acute ischemic stroke develop early neurologic
      worsening, which is associated with increased mortality and long-term functional
      disability. We investigated the predictive factors for neurologic deterioration
      in patients with acute ischemic stroke within 1 week of onset. We retrospectively
      investigated 643 patients who were admitted within 2 days of acute ischemic
      stroke between April 2007 and March 2010. Neurologic deterioration was defined as
      an increase of 4 points or more in the National Institutes of Health Stroke Scale
      (NIHSS) score within 1 week of admission. We retrieved data on demographic and
      clinical characteristics, medications, and stroke subtypes. Out of 537 patients,
      deterioration was noted in 64 patients (11.9%; deterioration group). Multivariate
      analysis identified history of myocardial infarction (P < .001), NIHSS score >=8
      at onset (P < .001), high leukocyte count (P = .035), low-density lipoprotein
      cholesterol >=140 mg/dL (P = .002), and hemoglobin A1c >=7% (P = .006) as
      significant factors associated with deterioration. Branch atheromatous disease
      was more frequent in the deterioration group, and >90% of patients with
      deterioration either were discharged to nursing home care or died. Multivariate
      analysis of magnetic resonance imaging findings identified internal
      carotid/middle cerebral artery occlusion (each P < .001), striate capsular
      infarction (P = .030), pontine infarction (P = .047), and lesion size of 15-30 mm
      (P = .011) as independent factors associated with deterioration. Stroke patients
      with a high low-density lipoprotein level, high hemoglobin A1c level on
      admission, a history of myocardial infarction, and high NIHSS score are at high
      risk for neurologic deterioration. Patients with multiple risk factors for
      deterioration can benefit most from intensive monitoring.

PMID- 21903419
TI  - Improvement of door-to-imaging time in acute stroke patients by implementation of
      an all-points alarm.
AB  - In patients with acute ischemic stroke, thrombolysis offers an opportunity to
      effectively reduce disability and dependency. The success of this treatment is
      time-dependent. The crucial diagnostic step before initiation of treatment is
      cerebral imaging. With the aim of reducing in-hospital delays, our hospital's
      interdisciplinary stroke management group implemented an all-points alarm to
      improve in-hospital time delay (the period between arrival to the emergency
      department and performance of cerebral imaging). The alarm simultaneously alerted
      all involved staff (from the neurologist to in-hospital transport) to the arrival
      of a patient potentially eligible for thrombolysis. Time delay, sociodemographic,
      and clinical data were assessed prospectively at 4 months before and 8 months
      after alarm implementation. Data were examined by analysis of covariance for both
      the intention-to-treat and per-protocol groups. During the assessment, 689
      patients with symptoms compatible with stroke arrived at our hospital. Among
      those, 111 patients (16%) were eligible for thrombolysis (median age, 71 years;
      median National Institutes of Health Stroke Scale score, 11; 44% female). Patient
      characteristics (ie, age, sex, insurance status, National Institutes of Health
      Stroke Scale score, cardiovascular risk factors, and prehospital delay) did not
      differ significantly before (n = 34) and after (n = 77) alarm implementation. The
      median "door-to-imaging time" for patients eligible for thrombolysis was
      significantly reduced, from 54 minutes before implementation of the alarm to 35
      minutes after implementation. Adjusted analysis of covariance demonstrated a
      significant influence of the intervention (P = .001) on differences in time
      delay. The proportion of ischemic stroke patients receiving thrombolysis rose
      from 42% to 66% (P = .04). The per-protocol analysis confirmed these results. The
      implementation of an all-points alarm can result in significant reduction of the
      time needed for in-hospital pathways for acute stroke patients.

PMID- 21903420
TI  - Recovery process and prognosis of aphasic patients with left putaminal
      hemorrhage: relationship between hematoma type and language modalities.
AB  - To elucidate the precise recovery process and prognosis of language functions in
      aphasic patients with left putaminal hemorrhage, we investigated 48 aphasic
      patients classified into 4 groups according to the location and extent of
      hematoma. The hematoma extended to the corona radiata in all patients,
      extracapsular in type I (12 cases), to the anterior limb in type II (10 cases),
      to the posterior limb in type III (12 cases), and to both limbs in type IV (14
      cases). The Standard Language Test for Aphasia was performed at 1 month, 3
      months, and 6 months after the attack. The type II, III, and IV patients were
      divided into 2 groups, with and without ventricular rupture of the hemorrhage. At
      3 and 6 months after the attack, the type I, II, and III patients showed
      significant improvement (P < .05) in all language modalities compared with the
      type IV patients. Most improvement in language modalities occurred in the first 3
      months. The evaluation of patients with ventricular rupture after 6 months
      revealed poor recovery (P < .05) in oral commands, visual commands, confrontation
      naming, sentence repetition, narratives, verbal fluency, and writing in type II
      and III patients. In type IV patients, this evaluation showed poor recovery (P <
      .05) only in oral and written naming (kanji words). No significant difference in
      prognostic outcome was observed between the surgical treatment group and the
      nonsurgical treatment group. The classification of hemorrhage may be useful in
      predicting the outcome of aphasia with putaminal hemorrhage and in guiding
      clinicians in providing effective instructions to patients and their relatives.

PMID- 21903421
TI  - Helicobacter pylori infection in patients with epilepsy.
AB  - BACKGROUND: The possible role of Helicobacter pylori (HP) infection in extra
      intestinal diseases has been suggested. The main purpose of this study was to
      determine the frequency of infection with HP in two groups of patients with
      epilepsy: patients with idiopathic generalized epilepsy (IGE) and patients with
      temporal lobe epilepsy (TLE), compared to healthy controls. METHODS: In this
      cross-sectional study a random sample of adult patients above 18 years of age
      with a diagnosis of IGE or TLE were recruited at the outpatient epilepsy clinic
      at Shiraz University of Medical Sciences, from January 2009 through June 2011. A
      group of healthy individuals were included as control group. For all patients and
      controls a urea breath test (UBT) was requested. RESULTS: Thirty-four patients
      with IGE, 28 patients with TLE and 33 individuals as control were recruited.
      Positive UBT was observed in 21 individuals (61.8%) with IGE, 50% (14 patients)
      of patients with TLE and 72.7% (24 individuals) in control group. The difference
      between patients with IGE and control group was not significant (P=0.3). The
      difference between patients with TLE and control group was not significant either
      (P=0.068). CONCLUSION: The rate of HP infection was not higher in patients with
      epilepsy compared to healthy individuals. At the moment, there is not enough
      epidemiological data to support the role of HP infection in patients with either
      IGE or TLE.

PMID- 21903422
TI  - Mapping a dynamic innate immunity protein interaction network regulating type I
      interferon production.
AB  - To systematically investigate innate immune signaling networks regulating
      production of type I interferon, we analyzed protein complexes formed after
      microbial recognition. Fifty-eight baits were associated with 260 interacting
      proteins forming a human innate immunity interactome for type I interferon (HI5)
      of 401 unique interactions; 21% of interactions were modulated by RNA, DNA, or
      LPS. Overexpression and depletion analyses identified 22 unique genes that
      regulated NF-kappaB and ISRE reporter activity, viral replication, or virus
      induced interferon production. Detailed mechanistic analysis defined a role for
      mind bomb (MIB) E3 ligases in K63-linked ubiquitination of TBK1, a kinase that
      phosphorylates IRF transcription factors controlling interferon production. Mib
      genes selectively controlled responses to cytosolic RNA. MIB deficiency reduced
      antiviral activity, establishing the role of MIB proteins as positive regulators
      of antiviral responses. The HI5 provides a dynamic physical and regulatory
      network that serves as a resource for mechanistic analysis of innate immune
      signaling.

PMID- 21903423
TI  - Increased sensitivity of antigen-experienced T cells through the enrichment of
      oligomeric T cell receptor complexes.
AB  - Although memory T cells respond more vigorously to stimulation and they are more
      sensitive to low doses of antigen than naive T cells, the molecular basis of this
      increased sensitivity remains unclear. We have previously shown that the T cell
      receptor (TCR) exists as different-sized oligomers on the surface of resting T
      cells and that large oligomers are preferentially activated in response to low
      antigen doses. Through biochemistry and electron microscopy, we now showed that
      previously stimulated and memory T cells have more and larger TCR oligomers at
      the cell surface than their naive counterparts. Reconstitution of cells and mice
      with a point mutant of the CD3zeta subunit, which impairs TCR oligomer formation,
      demonstrated that the increased size of TCR oligomers was directly responsible
      for the increased sensitivity of antigen-experienced T cells. Thus, we propose
      that an "avidity maturation" mechanism underlies T cell antigenic memory.

PMID- 21903424
TI  - Multilineage priming of enhancer repertoires precedes commitment to the B and
      myeloid cell lineages in hematopoietic progenitors.
AB  - Recent studies have documented genome-wide binding patterns of transcriptional
      regulators and their associated epigenetic marks in hematopoietic cell lineages.
      In order to determine how epigenetic marks are established and maintained during
      developmental progression, we have generated long-term cultures of hematopoietic
      progenitors by enforcing the expression of the E-protein antagonist Id2.
      Hematopoietic progenitors that express Id2 are multipotent and readily
      differentiate upon withdrawal of Id2 expression into committed B lineage cells,
      thus indicating a causative role for E2A (Tcf3) in promoting the B cell fate.
      Genome-wide analyses revealed that a substantial fraction of lymphoid and myeloid
      enhancers are premarked by the poised or active enhancer mark H3K4me1 in
      multipotent progenitors. Thus, in hematopoietic progenitors, multilineage priming
      of enhancer elements precedes commitment to the lymphoid or myeloid cell
      lineages.

PMID- 21903425
TI  - Eversion versus conventional carotid endarterectomy: a meta-analysis of
      randomised and non-randomised studies.
AB  - BACKGROUND: To compare eversion (ECEA) and conventional (CCEA) carotid
      endarterectomy from randomised and non-randomised studies. METHODS: Pooled odds
      ratios (ORs) with 95% confidence intervals (95%CIs) and numbers needed to treat
      (NNTs) were appropriately calculated. A sub-analysis was performed on studies
      directly comparing ECEA vs. patch CEA (PCEA). Meta-regression analysis was
      performed to examine the effect of potentially meaningful patient-related,
      procedure-related and definition-related modifiers. Power calculations were also
      conducted. RESULTS: A total of 21 studies were deemed eligible (8530 ECEA and
      7721 CCEA procedures), seven of which were randomised and 14 non-randomised. ECEA
      was associated with significant reduction in perioperative stroke (OR = 0.46,
      95%CI: 0.35-0.62, NNT = 68, 95%CI: 56-96), death (OR = 0.49, 95%CI: 0.34-0.69,
      NNT = 100, 95%CI: 85-185) and stroke-related death (OR = 0.40, 95%CI: 0.23-0.67,
      NNT = 147, 95%CI: 115-270); the results were replicated at the sub-analysis on
      PCEA. Concerning long-term outcomes, ECEA presented with a significant reduction
      in late carotid artery occlusion (OR = 0.48, 95%CI: 0.25-0.90, NNT = 143, 95%CI:
      100-769) and late mortality (OR = 0.76, 95%CI: 0.61-0.94, NNT = 40, 95%CI: 25
      167); the sub-analysis on PCEA replicated only the finding on late mortality.
      Meta-regression analysis did not point to significant effects mediated by the
      examined modifiers. Power calculations suggested adequate statistical power.
      CONCLUSIONS: ECEA compared to CCEA may be associated with a lower incidence in
      both short-term and long-term outcomes, which does not seem to be hampered by
      potentially meaningful modifiers.

PMID- 21903426
TI  - Endovascular stent-graft treatment for Stanford type A aortic dissection.
AB  - OBJECTIVE: The aim of the study is to summarise our experience of endovascular
      stent grafting for Stanford type A aortic dissection. DESIGN: Retrospective
      analysis at single centre. METHODS: From January 2001 to January 2009, we treated
      45 cases of Stanford type A aortic dissection with endovascular stent grafting.
      The entry tear was located at the ascending aorta in 10 cases (DeBakey type I),
      the aortic arch in 14 cases and the distal aortic arch or proximal descending
      aorta in 21 cases in which the ascending aorta was also involved by the
      dissection. RESULTS: The surgical success rate was 97.8% (44/45) and 30-day
      mortality rate was 6.7% (3/45). Type I endoleaks occurred in 10 cases: one
      patient died intra-operatively, four were successfully treated with ballooning,
      four were sealed with aortic cuffs and one case caused by left subclavian artery
      (LSA) reflux was sealed with an occluder. Average follow-up time was 35.5 +/- 5.4
      months. Up to the most recent review or death, 32 patients had complete
      thrombosis and 10 had partial thrombosis inside the false lumen. Two deaths
      occurred after 30-days postoperatively. CONCLUSION: Endovascular stent-graft
      treatment is a minimally invasive and effective method to treat Stanford type A
      aortic dissection.

PMID- 21903428
TI  - Immunohistochemical expression of matrix metalloproteinases 1, 2, 7, 9, and 26 in
      the calcifying cystic odontogenic tumor.
AB  - OBJECTIVE: The aim was to evaluate immunoexpression of matrix metalloproteinases
      (MMPs) 1, 2, 7, 9, and 26 in calcifying cystic odontogenic tumor (CCOT). STUDY
      DESIGN: Ten cases of CCOT were assessed by immunohistochemical expression of MMPs
      1, 2, 7, 9, and 26 in the parenchyma and stroma. Metalloproteinase
      immunoexpressions and their distribution pattern were semiquantitatively scored.
      RESULTS: MMPs were expressed in the parenchyma and stroma in all cases of CCOT.
      Regarding the percentage of immunostained parenchymal cells, MMPs 1, 7, and 9
      showed score 2 in 100% of cases. For MMP-2, there was a predominance of score 0
      (90%), whereas for MMP-26 immunostaining was varied. CONCLUSIONS: The staining of
      these metalloproteinases, with the exception of MMP-2, suggests their
      contribution to tumor growth and expansion. The presence of these
      metalloproteinases in stromal cells reveals the active participation of these
      cells in the degradation of the extracellular matrix, contributing to the growth
      of the tumor studied.

PMID- 21903429
TI  - Relationships between mandibular cortical indexes, bone mineral density, and
      osteoporotic fractures in Brazilian men over 60 years old.
AB  - OBJECTIVE: The aim of this study was to assess relationships between panoramic
      indexes, bone mineral density (BMD), and osteoporotic fractures in men >60 years
      old. STUDY DESIGN: Body height and weight, body mass index, lumbar spine and hip
      BMD, and the presence of osteoporotic fractures were determined in the 127
      studied men. Dental panoramic radiographs (DPRs) were used for measuring
      mandibular cortical indexes. RESULTS: BMDs were lower in patients with thinning
      and resorption of mandibular cortex. No association was found between mandibular
      indexes and the presence of osteoporotic fractures. In a forward stepwise
      logistic regression model, the odds of having a T score <=-2.5 was increased by
      1.97 times for every 1-mm reduction in average mandibular cortical width.
      CONCLUSIONS: DPRs could show pronounced thinning of the inferior mandibular
      cortices in men >60 years old. However, there was no apparent association between
      vertebral fragility fractures and the appearance of mandibular cortex in elderly
      men.

PMID- 21903430
TI  - Prevalence and on-farm risk factors for diarrhoea in meat lamb flocks in Western
      Australia.
AB  - Diarrhoea is a widespread problem for sheep enterprises worldwide. A cross
      sectional epidemiological study was conducted using a questionnaire to determine
      the prevalence of diarrhoea and associated risk factors where there was evidence
      of recent diarrhoea (active diarrhoea or fresh faecal soiling of breech fleece)
      for meat lambs on farms in southern Western Australia during 2010. The response
      rate was 41.4% (139/336). Evidence of recent diarrhoea was reported on 64.8% of
      farms, with a mean of 6.9% lambs affected per farm. Location of a farm and a
      higher annual rainfall were associated with an increased diarrhoea prevalence.
      Binary logistic regression analysis suggested that the drinking water source was
      associated with the incidence of diarrhoea, since lamb flocks supplied with dam
      water were 117 times (95% CI: 18.2, 754.8) more likely to have observed diarrhoea
      or fresh breech fleece faecal soiling than lamb flocks supplied with other
      sources of water. Faecal worm egg counts were used by 65% of respondents to
      determine whether an anthelmintic treatment was warranted and 74% of respondents
      administered a treatment to their meat lambs. In response to a range of diarrhoea
      scenarios presented to respondents (5%, 25% and 50% of the flock with evidence of
      recent diarrhoea), 15.1% would have elected to administer an anthelmintic
      treatment regardless of differences in prevalence.

PMID- 21903431
TI  - Rituximab in a childhood-onset idiopathic refractory chronic inflammatory
      demyelinating polyneuropathy.
AB  - Childhood-onset chronic inflammatory demyelinating polyneuropathy (CIDP) are
      generally responsive to conventional immunosuppressant treatments. However about
      20% of patients may be refractory to several treatments and the disease has poor
      outcome. Rituximab is becoming a promising treatment in selected adult cases of
      severe CIDPs. We report the effectiveness of Rituximab in a refractory childhood
      onset CIDP and we suggest this treatment as an effective choice in unresponsive
      childhood CIDP.

PMID- 21903432
TI  - Cranial magnetic resonance imaging findings of nutritional vitamin B12 deficiency
      in 15 hypotonic infants.
AB  - BACKGROUND: Nutritional vitamin B(12) deficieny is common among infants in the
      developing and underdeveloped countries. There is limited information concerning
      neuroimaging findings in infants with vitamin B(12) deficiency in the literature.
      AIMS: The aim of this study is to evaluate the cranial magnetic resonance imaging
      (MRI) changes and clinical characteristics of hypotonic infants due to vitamin
      B(12) deficiency. MATERIALS AND METHODS: A total of 15 infants with
      neuroradiologic investigations were diagnosed with nutritional B(12) vitamin
      deficiency. Cranial MRI was performed on all infants. RESULTS: Five infants were
      female (33%) and the mean age of infants was 12.3 +/- 5.5 months. Hypotonia and
      neurodevelopmental retardation were present in all patients. MRI demonstrated
      thinning of the corpus callosum in 6 (40%), cortical atrophy in 5 (33.3%), large
      sylvian fissures in 5 (33.3%), ventricular dilatation in 3 (20%), asymetric large
      lateral ventricle in 2 (13.3%) and delayed in myelination in 2 (13.3%) patients.
      Four infants had normal MRI findings. CONCLUSION: Because of the importance of
      vitamin B(12) in the development of the brain, MRI findings may be detected and
      useful in infants with vitamin B(12) deficiency.

PMID- 21903435
TI  - EPI - In the beginning.
AB  - The ideas and thoughts that resulted in the creation of EPI are recalled.

PMID- 21903433
TI  - Novel features in the evolution of adenylosuccinate lyase deficiency.
AB  - BACKGROUND: Adenylosuccinate lyase (ADSL) deficiency is an autosomal recessive
      disorder of the purine synthesis which results in accumulation of succinylpurines
      (succinyladenosine (S-Ado) and succinylamino-imidazole carboxamide riboside
      (SAICAr)) in body fluids. Patients present developmental delay, often accompanied
      by epilepsy and autistic spectrum disorders. OBJECTIVES: To describe atypical
      neurological features in the evolution of three novel unrelated cases of ADSL
      deficiency. PATIENTS: A 9-year-old boy with severe cognitive impairment and
      autistic behaviour received d-ribose therapy for one year. Drug withdrawal was
      associated with acute neurological deterioration, severe brain atrophy and
      demyelination on MRI. The second patient is a 5.5-year-old girl with mild
      developmental delay who presented a benign course with moderate cognitive
      impairment as the only feature in her evolution. The final patient is a 14-year
      old boy with severe cognitive impairment who developed drug-resistant epilepsy
      and bathing reflex seizures, progressive spasticity in the lower limbs and
      thoracic deformity. METHODS: SAICAr and S-Ado in urine were analysed by HPLC with
      diode array detection. Diagnosis was confirmed by molecular analysis of the ADSL
      gene. RESULTS: An elevation of S-Ado and SAICAr excretion in urine was detected
      in all three patients. The patients were homozygous for the missence change
      p.I369L and for the novel change p.M389V. CONCLUSION: Drug-resistant epilepsy and
      specific therapeutic interventions may modify the neurological outcome in ADSL
      deficiency. d-ribose must be considered with caution as, in our experience, it
      returns no clinical benefit and drug withdrawal can precipitate status
      epilepticus and acute neurological deterioration.

PMID- 21903436
TI  - THz-waves channeling in a monolithic saddle-coil for Dynamic Nuclear Polarization
      enhanced NMR.
AB  - A saddle coil manufactured by electric discharge machining (EDM) from a solid
      piece of copper has recently been realized at EPFL for Dynamic Nuclear
      Polarization enhanced Nuclear Magnetic Resonance experiments (DNP-NMR) at 9.4 T.
      The corresponding electromagnetic behavior of radio-frequency (400 MHz) and THz
      (263 GHz) waves were studied by numerical simulation in various measurement
      configurations. Moreover, we present an experimental method by which the results
      of the THz-wave numerical modeling are validated. On the basis of the good
      agreement between numerical and experimental results, we conducted by numerical
      simulation a systematic analysis on the influence of the coil geometry and of the
      sample properties on the THz-wave field, which is crucial in view of the
      optimization of DNP-NMR in solids.

PMID- 21903437
TI  - SIMPSON - an important driver for numerical simulations in solid-state NMR
      spectroscopy.
AB  - We present a historical recollection on the development of the software package
      SIMPSON (SIMulation Package for SOlid-state Nmr). This covers a brief description
      of the underlying ideas and events leading to creation of SIMPSON and numerous
      auxiliary programs as well as comments on its impact on the development and
      application of solid-state NMR in research laboratories world-wide.

PMID- 21903438
TI  - Short perspective on "NMR population inversion using a composite pulse" by M.H.
      Levitt and R. Freeman [J. Magn. Reson. 33 (1979) 473-476].
AB  - The invention of the composite pulse by Malcolm H. Levitt in 1978 is described
      from a personal perspective.

PMID- 21903439
TI  - Analysis of the GH content within archived dried blood spots of newborn screening
      cards from children diagnosed with growth hormone deficiency after the neonatal
      period.
AB  - OBJECTIVE: It is unknown whether GH secretion of children with growth hormone
      deficiency (GHD) is already diminished at birth. We aimed to determine the GH
      content within archived dried blood spots of newborn screening cards from
      children diagnosed with GHD at childhood. DESIGN: At our hospital, all children
      with the diagnosis of GHD and an actual age <10years were identified. For 16
      patients (mean age, 7.4years; range, 1.0-9.7), screening cards were available.
      The archived dried blood from the first 48 to 96h of life was eluated in buffer
      of a highly sensitive hGH-ELISA to measure the GH content. Reference values were
      calculated based on 600 anonymous newborn screening cards of different ages.
      RESULTS: Median GH content within the archived dried blood spots of the reference
      had declined by 30% during the first year and by further 35% during the next
      8.5years of storage. After correction for time of storage, four out of the 16
      archived dried blood spots of the GHD children contained low amounts of GH (<=5th
      percentile). Diminished GH secretion at birth was absent in isolated GHD, but
      associated with multiple pituitary hormone deficiency (MPHD) (P=0.0013), ectopic
      neurohypophysis (P=0.0013), lower GH test peak values (P=0.02) and higher weight
      at diagnosis (P=0.015). CONCLUSIONS: Children with isolated GHD have normal GH
      secretory capacity during the first week of life while the majority of children
      with MPHD and pituitary malformation were GH deficient immediately after birth.

PMID- 21903440
TI  - [Mothers experience in participating in the care of their hospitalised children].
AB  - OBJECTIVES: The purpose of this study was to describe the experience, the meaning
      and importance to them, of mothers participating in the care process of their
      child, as well as to identify interventions in which mothers were involved.
      METHOD: A qualitative approach was employed for this study, which was
      theoretically based on Symbolic Interactions and the Grounded Theory reference
      methodology. A semi-structured interview and observation were chosen as data
      collection techniques. The study included 18 mothers with hospitalised children.
      They were selected based on inclusion criteria: mothers with children
      hospitalised 5 or more days, and with a willingness to participate. The number of
      participants was defined using the criterion of data saturation. The data was
      analysed using the program Nvivo8. RESULTS: Mothers understood the participation
      as an obligation and an aid to nurses. They also considered it as a contribution
      to the personal care of their children, for their well-being and for continuity
      of the parental role. The care in which the mothers were involved were those of
      family care, already developed in the home. They developed other forms of care,
      which were delegated by nurses without negotiation. The confusion of roles and
      the non-distribution of power caused anxiety in mothers when confronted with new
      forms of care. CONCLUSIONS: The mothers considered their participation in their
      child's care as very important, but this involvement was characterised by a
      continuation of the care provided at home. They developed other forms of care but
      were not fully involved.

PMID- 21903441
TI  - [How present ART' results: questions' list to French ART professionals and
      application on Amiens' ART results].
AB  - OBJECTIVES: ART transparency of results and ways to submit are in centre of
      present biologists and clinical cares. This work aims at identifying ART results'
      presentation pertinent tests. PATIENTS AND METHODS: At first time, we propose a
      questions' list to French ART professionals. Next, we apply results on Amiens'
      ART center 2006, 2007 and 2008 IVF parameters. RESULTS: One hundred and twenty
      questions' lists were analysed. Ninety percent of interrogated people were in
      favour of the results' center public communication. Most quoting criterions hold
      to define a reference population are (percentage of favourable opinions):
      IVF/ICSI treatment (96%), first of second rank's attempts (71%), women age less
      than 35 years old (68%), one or two top embryos quality transfer (60%). In 2007,
      2008 and 2009, we made 1123 tentative IVF+/-ICSI in Amiens' ART center. Pregnancy
      rates were analysed for these years with criterions next quoting as most
      pertinent (women's age and rank's attempt), and in function of puncture retrieval
      oocytes number and indications. DISCUSSION AND CONCLUSION: Most of professionals
      are in favour of ART transparency of results. All would like that results
      presentation holds to special criterions to allow a fair comparison. Pregnancy
      predictive factors, which are women age, rank attempt, puncture retrieval oocytes
      number, seem to be main criterions for evaluation. These criterions pertinence
      has been shown thanks to Amiens ART center results.

PMID- 21903443
TI  - Motor improvement with bilateral subthalamic nucleus deep brain stimulation in a
      patient with levodopa-responsive secondary parkinsonism.
AB  - At many centers, subthalamic nucleus (STN) deep brain stimulation (DBS) is not
      considered for patients with secondary forms of parkinsonism, due to higher
      expected rates of treatment failure. We present the case of a woman with
      secondary parkinsonism that developed following a Measles, Mumps, and Rubella
      (MMR) vaccination, who experienced sustained improvement in motor function
      following STN DBS. Despite the diagnosis of a secondary parkinsonism, this
      patient responded well to dopaminergic therapy, a good predictor of DBS outcome
      in patients with idiopathic Parkinson's disease. This case suggests that DBS may
      be considered in the setting of secondary parkinsonism if such patients have
      levodopa-responsive symptoms.

PMID- 21903442
TI  - Load/strain distribution between ulna and radius in the mouse forearm compression
      loading model.
AB  - Finite element analysis (FEA) of the mouse forearm compression loading model is
      used to relate strain distributions with downstream changes in bone formation and
      responses of bone cells. The objective of this study was to develop two FEA
      models - the first one with the traditional ulna only and the second one in which
      both the ulna and radius are included, in order to examine the effect of the
      inclusion of the radius on the strain distributions in the ulna. The entire mouse
      forearm was scanned using microCT and images were converted into FEA tetrahedral
      meshes using a suite of software programs. The performance of both linear and
      quadratic tetrahedral elements and coarse and fine meshes were studied. A load of
      2N was applied to the ulna/radius model and a 1.3N load (based on previous
      investigations of load sharing between the ulna and radius in rats) was applied
      to the ulna only model for subsequent simulations. The results showed differences
      in the cross sectional strain distributions and magnitude within the ulna for the
      combined ulna/radius model versus the ulna only model. The maximal strain in the
      combined model occurred about 4mm toward the distal end from the ulna mid-shaft
      in both models. Results from the FEA model simulations were also compared to
      experimentally determined strain values. We conclude that inclusion of the radius
      in FE models to predict strains during in vivo forearm loading increases the
      magnitude of the estimated ulna strains compared to those predicted from a model
      of the ulna alone but the distribution was similar. This has important
      ramifications for future studies to understand strain thresholds needed to
      activate bone cell responses to mechanical loading.

PMID- 21903444
TI  - Intra-individual variations in the bifurcation of the radial nerve and the length
      of the posterior interosseous nerve.
AB  - Anatomical literature on the radial nerve predominantly features inter-individual
      variations, with comparatively few studies investigating intra-individual
      variations. The radial nerve has a complex and variable course, particularly in
      relation to the location at which the nerve bifurcates to form the superficial
      branch of the radial nerve and the posterior interosseous nerve. Variations of
      the radial nerve may change the way the nerve and its branches, their blood
      supply and nerve transmission respond to forces. This study investigated the
      presence of intra-individual differences in the bifurcation point of the radial
      nerve and the length of the posterior interosseous nerve from the bifurcation to
      the radial tunnel. Eighteen embalmed human cadavers were dissected to reveal the
      radial nerve. Measurements were taken from the level of the lateral humeral
      epicondyle to the bifurcation of the radial nerve, and from the bifurcation to
      the radial tunnel. All cadavers presented with intra-individual variations
      between the left and right limbs. Significant differences were found between the
      left and right limbs for the measurement from the lateral humeral epicondyle to
      the bifurcation (median difference = 18.0 mm; p = 0.016) but not for the
      measurement from the bifurcation to the radial tunnel (median difference = 7.0
      mm; p = 0.396). In conclusion, the location of the radial nerve bifurcation is
      subject to both intra- and inter-individual variations. Its specific relationship
      to the lateral humeral epicondyle also varies, occurring both distal and proximal
      to the level of the epicondyle. Clinical implications of these findings warrant
      further investigation.

PMID- 21903445
TI  - The relationships between measures of stature recovery, muscle activity and
      psychological factors in patients with chronic low back pain.
AB  - Individuals with low back pain (LBP) often exhibit elevated paraspinal muscle
      activity compared to asymptomatic controls during static postures such as
      standing. This hyperactivity has been associated with a delayed rate of stature
      recovery in individuals with mild LBP. This study aimed to explore this
      association further in a more clinically relevant population of NHS patients with
      LBP and to investigate if relationships exist with a number of psychological
      factors. Forty seven patients were recruited from waiting lists for
      physiotherapist-led rehabilitation programmes. Paraspinal muscle activity while
      standing was assessed via surface electromyogram (EMG) and stature recovery over
      a 40-min unloading period was measured on a precision stadiometer. Self-report of
      pain, disability, anxiety, depression, pain-related anxiety, fear of movement,
      self-efficacy and catastrophising were recorded. Correlations were found between
      muscle activity and both pain (r=0.48) and disability (r=0.43). Muscle activity
      was also correlated with self-efficacy (r=-0.45), depression (r=0.33), anxiety
      (r=0.31), pain-related anxiety (r=0.29) and catastrophising (r=0.29) and was a
      mediator between self-efficacy and pain. Pain was a mediator in the relationship
      between muscle activity and disability. Stature recovery was not found to be
      related to pain, disability, muscle activity or any of the psychological factors.
      The findings confirm the importance of muscle activity within LBP, in particular
      as a pathway by which psychological factors may impact on clinical outcome. The
      mediating role of muscle activity between psychological factors and pain suggests
      that interventions that are able to reduce muscle tension may be of particular
      benefit to patients demonstrating such characteristics, which may help in the
      targeting of treatment for LBP.

PMID- 21903446
TI  - The role of mitochondrial respiration in salinity tolerance.
AB  - NaCl is the most abundant salt in salinity-affected land. The ability of plants
      to sift the water table, limit NaCl uptake, compartmentalise Na+/Cl- ions and
      prevent negative ionic and osmotic effects on cell function, are the foundations
      of salinity tolerance mechanisms. In this review, we show that although the
      quantitative response of respiratory rate to changes in salt concentration is
      complex, the properties of respiratory processes are crucial for tolerance during
      ion exclusion and tissue tolerance. We consider whole-plant gas exchange and
      carbon balance analysis alongside the salt responses of mitochondrial properties
      and genetic studies manipulating respiratory processes. We showcase the
      importance of efficient ATP generation, dampened reactive oxygen species and
      mitochondrial osmolytes for salinity tolerance in plants.

PMID- 21903447
TI  - Decreased cognitive functioning in patients with advanced oral squamous cell
      carcinoma.
AB  - Cognitive impairment causes a delay in diagnosis and treatment of the various
      cancer entities, resulting in reduced surgical outcomes and patient survival.
      However, no investigations have been carried out as to whether an association
      exists between cognitive functioning and tumour size in patients with oral
      squamous cell carcinoma (OSCC). In this study, 46 patients with OSCC were
      evaluated by using a screening test for dementia, consisting of a combination of
      the mini-mental state examination and the clock test (81% sensitivity and 90%
      specificity). Test scores were correlated with tumour size according to the TNM
      staging system, which was categorized as being either limited (T1, T2; n=24) or
      advanced (T3, T4; n=22). No difference in age (P=0.172), sex (P=0.330), the
      percentage of drinkers (P=0.090) or the percentage of smokers (P=0.484) was
      evident between the groups. Patients with advanced tumour size scored
      significantly lower (median 5.5 of 9 possible points) when compared with those
      having tumours of a limited size (median 9 of 9 possible points; P=0.005). The
      median score of patients with T3/T4 tumours suggested the need for comprehensive
      neuropsychological evaluations for dementia. In conclusion, this study has
      demonstrated the correlation of reduced cognitive functioning in patients with
      advanced OSCC. As a consequence, instructions for the identification of early
      signs and of symptoms of oral cancer are strongly recommended for relatives and
      nursing staff of patients with cognitive impairment. Such patients might need
      immediate treatment for oral cancer but might not be able to understand the
      significance of their symptoms and therefore present late, often too late.

PMID- 21903448
TI  - Nuclear translocation of MRP1 contributes to multidrug resistance of
      mucoepidermoid carcinoma.
AB  - Multidrug resistance-related protein 1 (MRP1 or ABCC1), a membrane-bound energy
      dependent efflux transporter, is overexpressed in several kinds of multidrug
      resistant cell lines and related to multidrug-resistance (MDR) of various
      cancers. In this study, we investigated whether MRP1 was involved in the
      chemoresistance of mucoepidermoid carcinoma (MEC). We demonstrated that down
      regulation of MRP1 in MC3/5FU, a drug-resistant MEC cell line, by RNA
      interference increased the drug sensitivity of the cells to 5-fluorouracil,
      doxorubicin, pharmorubicin, bleomycin-A5, cis-platinum and taxol. However, no
      significant quantitative difference of MRP1 mRNA and protein expression was found
      between MC3/5FU cells and its parental cell line (MC3) as determined by RT-PCR
      and Western blot. Interestingly, MRP1 was translocated from the cytoplasmic
      membrane of the MC3 cells to the nuclei of MC3/5FU cells as revealed by indirect
      immunofluorescence staining. Furthermore, MRP1 down-regulation mainly decreased
      the nuclear expression of MRP1 rather than the cytoplasmic membrane expression.
      Our results suggested that MRP1 was involved in the chemoresistance of MEC and
      MRP1 may confer drug-resistance by a mechanism associated with its nuclear
      translocation.

PMID- 21903449
TI  - The impact of EGFR stimulation and inhibition on BPDE induced DNA fragmentation
      in oral/oropharyngeal mucosa in vitro.
AB  - Still, the vast majority of head and neck squamous cell carcinoma (HNSCC) can be
      linked to the "traditional" risk factors tobacco smoke and alcohol consumption.
      These tumors are believed to be the results of multiple years of carcinogenic
      impact on upper aerodigestive tract mucosa. The frequent observation, that one
      patient suffers from several synchronous cancers, multiple local recurrences, and
      second primary tumors led to the concept of field cancerization, first introduced
      by Slaughter and colleagues in 1953. As underlying molecular events, genetic
      instability, loss of heterozygosity, amplification, deletion, up- and down
      regulation of oncogenes and/or tumor suppressor genes were revealed. One of the
      best studied oncogenic features of head and neck carcinogenesis are high
      expression levels of epidermal growth factor receptor (EGFR). Enhanced expression
      of the receptor was detected in histologically normal mucosa from HNSCC patients
      and increasing levels during the progress from hyperplasia to dysplastic lesion
      and invasive carcinoma were demonstrated. Whereas nearly all of our knowledge
      about EGFR biology in HNSCC is based on preclinical and clinical studies
      investigating receptor inhibitors, little is known about cause and function of
      EGFR in premalignant mucosa. In this study we show, that EGFR stimulation
      significantly decreases carcinogen induced DNA damage in normal mucosa from HNSCC
      patients and that this effect is completely abrogated adding an anti-EGFR
      antibody before stimulation, while there was no effect in non-tumor controls. The
      effect of EGFR inhibition was contrary. In non-tumor controls, blocking the
      receptor with an antibody significantly decreased DNA damage, whereas in cases no
      effect was seen. Our results indicate an important role of the receptor during
      chemical carcinogenesis. On the basis of this study we suppose, that increasing
      EGFR levels during head and neck carcinogenesis can be interpreted as a
      physiological response to permanent carcinogen impact on the mucosa.

PMID- 21903450
TI  - Hyaluronic acid-paclitaxel conjugate inhibits growth of human squamous cell
      carcinomas of the head and neck via a hyaluronic acid-mediated mechanism.
AB  - Chemotherapeutic regimens incorporating taxanes significantly improve outcomes
      for patients with squamous cell carcinomas of the head and neck (SCCHN). However,
      treatment with taxanes is limited by toxicities, including bone marrow
      suppression and peripheral neuropathies. We proposed that conjugating taxanes to
      targeting carrier molecules would increase antitumor efficacy and decrease
      toxicity. The cell surface proteoglycan, CD44, is expressed on most SCCHNs, and
      we hypothesized that it is an attractive candidate for targeted therapy via its
      natural ligand, hyaluronic acid (HA). We determined whether HA-paclitaxel
      conjugates were able to decrease tumor growth and improve survival in orthotopic
      nude mouse human SCCHN xenograft models. HA-paclitaxel concentration-dependent
      growth inhibition of human SCCHN cell lines OSC-19 and HN5 in vitro, very
      similarly to free paclitaxel treatment. Tumor cell uptake of FITC-labeled HA
      paclitaxel was significantly blocked with free HA, indicating the dependence of
      uptake on CD44. HA-paclitaxel administered intravenously once per week for three
      weeks at 120 mg/kg paclitaxel equivalents, far above the paclitaxel maximum
      tolerated dose, exerted superior tumor growth control to that of paclitaxel in
      both orthotopic OSC-19-luciferase and HN5 xenograft models in vivo. Mouse
      survival following HA-paclitaxel administration was prolonged compared with that
      of controls in mice implanted with either of these xenografts. Mice treated with
      HA-paclitaxel displayed increased TUNEL(+) cells in tumor tissue, as well as
      markedly reduced microvessel density compared to those treated with free
      paclitaxel. No acute histopathological changes were observed in mice treated with
      HA-paclitaxel. Thus, we conclude that HA-paclitaxel effectively inhibits tumor
      growth in human SCCHN xenografts via an HA-mediated mechanism and this conjugate
      should be considered for further preclinical development for this disease.

PMID- 21903451
TI  - An update on plant membrane rafts.
AB  - The dynamic segregation of membrane components within microdomains, such as the
      sterol-enriched and sphingolipid-enriched membrane rafts, emerges as a central
      regulatory mechanism governing physiological responses in various organisms. Over
      the past five years, plasma membrane located raft-like domains have been
      described in several plant species. The protein and lipid compositions of
      detergent-insoluble membranes, supposed to contain these domains, have been
      extensively characterised. Imaging methods have shown that lateral segregation of
      lipids and proteins exists at the nanoscale level at the plant plasma membrane,
      correlating detergent insolubility and membrane-domain localisation of
      presumptive raft proteins. Finally, the dynamic association of specific proteins
      with detergent-insoluble membranes upon environmental stress has been reported,
      confirming a possible role for plant rafts as signal transduction platforms,
      particularly during biotic interactions.

PMID- 21903452
TI  - Synthesis and characterization of cadmium selenide nanoparticles loaded on
      activated carbon and its efficient application for removal of muroxide from
      aqueous solution.
AB  - In the first, Cadmium selenide Nanoparticle loaded on activated carbon (CdSe-NP
      AC) has been synthesized and characterized by different techniques including XRD
      and SEM. Then, this new adsorbent successfully has been applied for the removal
      of muroxide (MO) from aqueous solution in batch studies, while the effect of
      various experimental parameters like initial pH (pH(0)), contact time, amount of
      (CdSe-NP-AC) and initial MO concentration (C(0)) on its removal percentage was
      examined by one at a time optimization method. It was found following
      optimization of variable, the adsorption of MO onto (CdSe-NP-AC) followed pseudo
      second-order kinetics and show Tempkin and Langmuir models for interpretation of
      experimental data. It was observed that by increasing the temperature the removal
      percentage was improved and the positive change in entropy (DeltaS degrees ) and
      heat of adsorption (DeltaH degrees ) show the endothermic nature of process,
      while the high negative value in Gibbs free energy change (DeltaG degrees )
      indicates the feasible nature of adsorption process.

PMID- 21903453
TI  - FTIR spectroscopic, thermal and XRD characterization of hydroxyapatite from new
      natural sources.
AB  - The inorganic constituents of 5 different plants (leaves and stalks) were
      investigated by using Fourier transformer infrared spectroscopy (FTIR), X-ray
      diffraction (XRD) and thermal analysis including thermal gravimetric analysis
      (TGA), derivative thermogravimetry (DTG) and differential scanning calorimetry
      (DSC). These plants are Catha edulis (Khat), basil, mint, green tea and
      trifolium. The absorption bands of carbonate ions CO(3)(2-) was exhibited at 1446
      cm(-1), and the phosphate ions PO(4)(3-) was assigned at 1105 and 1035 cm(-1). At
      high temperatures (600, 700 and 600 degrees C) further absorption bands of the
      phosphate ions PO(4)(3-) was assigned at the frequencies 572, 617, 962, 1043 and
      1110 cm(-1) and the vibrational absorption band of the carbonate ions CO(3)(2-)
      was assigned at 871, 1416 and 1461 cm(-1). X-ray diffraction and thermal analysis
      confirm the obtained results of FITR. Results showed that the main inorganic
      constituents of C. edulis and basil leaves are hydroxyapatite whereas the
      hydroxyapatite content in the other plant samples is less than that in case of C.
      edulis and basil plant leaves.

PMID- 21903454
TI  - FT-IR, FT-Raman spectra, density functional computations of the vibrational
      spectra and molecular conformational analysis of 2,5-di-tert-butyl-hydroquinone.
AB  - The purpose of finding conformer among six different possible conformers of 2,5
      di-tert-butyl-hydroquinone (DTBHQ), its equilibrium geometry and harmonic
      wavenumbers were calculated by the B3LYP/6-31G(d,p) method. The infrared and
      Raman spectra of DTBHQ were recorded in the region 400-4000 cm(-1) and 50-3500
      cm(-1), respectively. In addition, the IR spectra in CCl(4) at various
      concentrations of DTBHQ are also recorded. The computed vibrational wavenumbers
      were compared with the IR and Raman experimental data. Computational calculations
      at B3LYP level with two different basis sets 6-31G(d,p) and 6-311++G(d,p) are
      also employed in the study of the possible conformer of DTBHQ. The complete
      assignments were performed on the basis of the potential energy distribution
      (PED) of the vibrational modes, calculated using VEDA 4 program. The general
      agreement between the observed and calculated frequencies was established.

PMID- 21903455
TI  - Microwave assisted synthesis, spectroscopic, electrochemical and DNA cleavage
      studies of lanthanide(III) complexes with coumarin based imines.
AB  - The present work stems from our interest in the synthesis, characterization and
      biological evaluation of lanthanide(III) complexes of a class of coumarin based
      imines which have been prepared by the interaction of hydrated lanthanide(III)
      chloride with the sodium salts of 3-acetylcoumarin thiosemicarbazone (ACTSZH) and
      3-acetylcoumarin semicarbazone (ACSZH) in 1:3 molar ratio using thermal as well
      as microwave method. Characterization of the ligands as well as the metal
      complexes have been carried out by elemental analysis, melting point
      determinations, molecular weight determinations, magnetic moment, molar
      conductance, IR, (1)H NMR, (13)C NMR, electronic, EPR, X-ray powder diffraction
      and mass spectral studies. Spectral studies confirm ligands to be monofunctional
      bidentate and octahedral environment around metal ions. The redox behavior of one
      of the synthesized metal complex was investigated by cyclic voltammetry. Further,
      free ligands and their metal complexes have been screened for their antimicrobial
      as well as DNA cleavage activity. The results of these findings have been
      presented and discussed.

PMID- 21903456
TI  - Prediction of the rovibrational emission spectroscopy of B2Sigma(+)-X2Sigma(+)
      system in 12C17O+.
AB  - An analytical formula based on the Herzberg's conventional rovibrational energy
      levels for diatomic system is proposed by taking multiple differences of spectral
      lines to predict the R-branch high-lying rovibrational emission spectroscopy,
      where only 15 accurate known transition lines and rotational constants D(v'),
      D(v'') are needed. Using the formula, the R(11ee) and R(22ff) branches of (0, 2)
      and (0, 3) transition bands in the B(2)Sigma(+)-X(2)Sigma(+) system of
      (12)C(17)O(+) are studied. The results show that not only the relatively lower
      order rovibrational transition lines given by experiments are reproduced but also
      the higher and the absent spectral lines are correctly predicted for each band.

PMID- 21903457
TI  - A physiochemical study of azo dyes: DFT based ESIPT process.
AB  - Azo linked dye derivatives were synthesized and characterized by NMR, mass and
      elemental analysis. An excited state intramolecular proton transfer (ESIPT) in
      hydroxy Schiff base has been analyzed, and found that two distinct ground state
      isomers of I and II are responsible for the observed dual emission. DFT
      calculation on energy, dipole moment, charge distribution of the rotamers in the
      ground and excited states support the ESIPT process. PES calculation indicates
      that the energy barrier for the interconversion of two rotamers is too high in
      the excited state than the ground state. By varying the addition of base
      concentration to hydroxy Schiff base, two isobestic points were found which
      confirm the equilibrium among the trans enol form, anion and the cis enol form.
      Fluorescence quenching with metal ions reveal that hydroxy Schiff base can be
      used as a new fluorescence sensor to detect the Cu(2+) ion.

PMID- 21903458
TI  - Mercapto thiadiazole-based sensor with colorimetric specific selectivity for AcO-
      in aqueous solution.
AB  - A novel acetate selective anion sensor 3 based on azophenol and mercapto
      thiadiazole had been designed and synthesized. Sensor 3 behaves a single
      selectivity and sensitivity in the recognition for AcO(-) anion over other anions
      such as F(-), Cl(-), Br(-), I(-), H(2)PO(4)(-), HSO(4)(-) and ClO(4)(-) by naked
      eyes and UV-vis spectra changes in aqueous solution (H(2)O/DMSO, 5:5, v/v). The
      color of the solution containing sensor 3 had an obvious change from colorless to
      orange only after the addition of AcO(-) in aqueous solution while other anions
      did not cause obvious color change. (1)H NMR titration results revealed that the
      binding process includes two steps: (i) hydrogen bonding interactions (for small
      quantities of acetate) and (ii) proton transfer between the sensor 3 and the
      coordinated anion (for high quantities of acetate). The association constant K(a)
      was 7.35*10(3) M(-1). The detection limitation of AcO(-) with the sensor 3 was
      1.0*10(-6) mol L(-1).

PMID- 21903459
TI  - Nucleos(t)ide analogue treatment reduces apoptotic activity in patients with
      chronic hepatitis B.
AB  - BACKGROUND: Reduction of necroinflammatory activity is a major goal of antiviral
      therapy of patients with chronic hepatitis B. Serum ALT does not detect all forms
      of cell death. OBJECTIVES: To analyze dynamics of novel serum cell death markers
      for apoptosis and necrosis in association with virologic response to
      nucleos(t)ide (Nuc) analogue treatment. STUDY DESIGN: Quantification of the M30
      apoptosis neoepitope and the cytokeratin-18 (M65-necrosis) serum levels before
      and during treatment of patients with chronic hepatitis B with Nuc (n = 26).
      RESULTS: Before treatment, M30-apoptotic activity was significantly correlated
      with M65-necrosis and fibrosis but not with serum ALT. During therapy with Nucs,
      cell death parameters M30-apoptosis, M65-necrosis, and ALT declined in
      association with virologic response. The most frequent cell death pattern was
      simultaneous decline of ALT and M30-apoptosis which occurred more frequently in
      patients with HBs-Antigen decline than in patients with HBs-Antigen increase
      during treatment (87.5% vs. 40.0%; p = 0.024). ALT decline in association with
      increase of M30 apoptosis was frequent in patients with HBs-Antigen increase
      during treatment (36.3%) but was not observed in patients with HBs-Antigen
      decline during treatment. CONCLUSION: Decline of cell death parameters in
      association with decline of HBV-DNA and HBs-Antigen indicates a reduction in
      overall cell death activity during Nuc treatment supporting the concept that
      response to Nuc therapy reduces necroinflammatory activity and progression of
      liver disease.

PMID- 21903460
TI  - Cortical pattern of complex but not simple movements is affected in writer's
      cramp: a parametric event-related fMRI study.
AB  - OBJECTIVE: Patients with writer's cramp (WC) were studied for differences in
      cortical activation during movements likely to induce WC (complex movements) and
      movements which rarely lead to dystonia (simple movements). METHODS: Eleven WC
      patients (10F, 1M, mean age 41.5 +/- (SD)7.2 years) and eleven age matched
      controls were examined for Blood oxygenation-level dependent (BOLD) 1.5 T fMRI.
      The complex task consisted of writing a single letter or random drawing using an
      especially adapted joystick with the line of trajectory visualized or hidden. The
      simple task consisted of self-initiated fingers flexion/extension using the
      affected hand. RESULTS: Unlike the controls, WC patients performing complex
      movements exhibited a lower BOLD signal in the primary sensorimotor cortex and in
      the posterior parietal cortex bilaterally. A hypoactivation was also observed in
      the right secondary somatosensory area, in the right anterior insula and in the
      left premotor cortex (p < 0.05 corrected). No significant inter-group differences
      were found for simple movements. CONCLUSIONS: Although WC patients' complex
      movements during fMRI were never associated with dystonic cramp, they exhibited
      an abnormally low cortical activity. This phenomenon was not observed in simple
      movements and was unrelated to the character of handwriting or to visual
      feedback. SIGNIFICANCE: Our results support the dualistic behavior in the
      sensorimotor system in WC.

PMID- 21903461
TI  - Stretch reflex responses in Complex Regional Pain Syndrome-related dystonia are
      not characterized by hyperreflexia.
AB  - OBJECTIVE: To evaluate if hyperreflexia (exaggerated reflexes) due to
      disinhibition is associated with dystonia in Complex Regional Pain Syndrome
      (CRPS). METHODS: Stretch reflexes at the wrist were assessed in healthy controls
      (n=10) and CRPS-patients with dystonia (n=10). Subjects exerted a wrist flexion
      torque of 5% of maximum voluntary contraction torque (T(MVC)) to a manipulandum
      which applied ramp-and-hold stretches to the wrist flexors. Since reflex
      responses scale with background contraction, controls additionally performed the
      task at 1% and 3% T(MVC) to attain similar torques as patients who have reduced
      T(MVC). The M1 onset and the magnitudes of the short latency M1 and long latency
      M2 were assessed using the electromyographic signals (EMG) of the flexor carpi
      radialis. EMG of the extensor carpi radialis was recorded to monitor
      cocontraction. RESULTS: Compared to controls, patients had a substantially
      reduced T(MVC). Ramp velocity had a significant effect on M1 onset time and
      magnitude. CONCLUSIONS: Since M1 magnitude decreased with flexion torque, no
      significant difference was found between patients and controls at 5% T(MVC),
      while comparison at similar absolute torques (controls at 1% T(MVC)) resulted in
      significantly smaller M1 magnitudes for patients with dystonia. SIGNIFICANCE:
      This study suggests that CRPS-patients with dystonia are not hyperreflexive.

PMID- 21903462
TI  - Exogenous and endogenous orienting of visuospatial attention in P300-guided brain
      computer interfaces: a pilot study on healthy participants.
AB  - OBJECTIVE: Studies on brain computer interfaces (BCIs) have been mainly concerned
      with algorithm improvement for better signal classification. Fewer studies,
      however, have addressed to date the role of cognitive mechanisms underlying the
      elicitation of brain-signals in BCIs. We tested the effect of visuospatial
      attention orienting on a P300-guided BCI, by comparing the effectiveness of three
      visual interfaces, which elicited different modalities of visuospatial attention
      orienting (exogenous vs. endogenous). METHODS: Twelve healthy participants
      performed 20 sessions, using the abovementioned P300-guided BCI interfaces to
      control a cursor. Brain waves were recorded on each trial and were subsequently
      classified on-line using an ad hoc algorithm. Each time the P300 was correctly
      classified, the cursor moved towards the target position. RESULTS: The
      "endogenous" interface was associated with significantly higher performance than
      the other two interfaces during the testing sessions, but not in the follow-up
      sessions. CONCLUSIONS: Endogenous visuospatial attention orienting can be
      effectively implemented to increase the performance of P300-guided BCIs.
      SIGNIFICANCE: The study of visuospatial attention underlying participants'
      performance is essential for implementing efficient visual BCIs.

PMID- 21903463
TI  - Quantification and localization of EEG interictal spike activity in patients with
      surgically removed epileptogenic foci.
AB  - OBJECTIVE: To demonstrate if interictal spike activity was localized within the
      resected area in surgically treated epilepsy patients; and if there is
      correspondence between the degree of localization and improvement after surgery.
      METHODS: We analyzed long-term EEGs from 34 patients. Interictal spikes were
      grouped in clusters and averaged according to morphology and topography. The
      relative contribution of each cluster to the total number of spikes in each
      patient was estimated. Dipole and distributed EEG source localization of each
      cluster was made. The percentage of spike activity localized within the site of
      resection (SR) during the onset was estimated. The relationship between the
      percentage of activity within SR and the surgery outcome was assessed. RESULTS:
      Fourteen patients had 90-100% of spikes within SR, 9 had 50-89%. Most patients
      with more than 50% of activity localized within SR were seizure free, while the 5
      patients who had all activity localized outside SR were not seizure free.
      CONCLUSIONS: Localization of clusters containing the largest quantity of
      interictal spikes during onset generally corresponded to the likely location of
      the epileptogenic cortex. SIGNIFICANCE: Computer-assisted EEG source localization
      with our methodology can be a useful adjunct for the evaluation of candidates for
      epilepsy surgery.

PMID- 21903465
TI  - Efficient hydrogen production from acetate through isolated Rhodobacter
      sphaeroides.
AB  - Photosynthetic bacteria produce hydrogen from lactate and acetate that are
      products of hydrogen producing bacteria in the dark. Thus, their coculture is a
      promising method for hydrogen production. However, the hydrogen production yield
      from acetate of Rhodobacter sphaeroides RV, which has been shown to possess the
      highest yield and hydrogen production rate, is low as compared to that from
      lactate. Photosynthetic bacteria that produce hydrogen from acetate as well as
      lactate were screened from lakes and swamps in the Tokyo and Chiba areas in
      Japan. Seventy-six strains of photosynthetic bacteria were obtained and the
      analysis of their 16S rRNA gene sequences revealed that they belong to R.
      sphaeroides. Among the isolated bacteria, R. sphaeroides HJ produced the highest
      amount of hydrogen from acetate and lactate. The HJ strain produced a 2300+/
      93ml/L-broth of hydrogen from 75mM acetate consumed during for 120h of
      fermentation. The amount of hydrogen and the yield from acetate were 1.9 and 2.1
      times higher, respectively, than those of R. sphaeroides RV. The amount and yield
      of hydrogen, produced by R. sphaeroides HJ from lactate were similar to those
      produced by R. sphaeroides RV. Since the amount and yield of produced hydrogen by
      the HJ strain were similar regardless of the substrate (acetate or lactate), its
      metabolic pathway could have a key to increasing hydrogen production from
      acetate.

PMID- 21903464
TI  - Quantification of motor unit action potential energy.
AB  - OBJECTIVE: Motor unit action potentials (MUAPs) recorded by needle electrode
      reflect the functional state of the motor unit and its force-generating capacity,
      and are usually described morphologically (e.g. amplitude, duration). However,
      since the purpose of motor unit activation is force generation, MUAP energy seems
      a more physically meaningful measurement. METHODS: MUAPs were obtained by multi
      MUAP decomposition of real interference patterns taken from human patients with
      neurological diseases. The energy content of each MUAP was measured from a time
      frequency representation (TFR), specifically the Choi-Williams distribution, and
      compared with the standard MUAP morphological measure, the Size Index. The sample
      included normal, neurogenic, and myopathic MUAPs, from 11 patients. RESULTS:
      There is an exponential distribution of energy within a sample of MUAPs and a
      strong exponential relationship between the Size Index and MUAP energy was
      observed. CONCLUSIONS: The energy content of a MUAP can be quantified and
      corresponds very well with the current quantitative standard. Energy is a
      possible addition to MUAP quantification. SIGNIFICANCE: MUAPs could be classified
      as having normal, large (neurogenic), or low (myopathic) energy. MUAP energy has
      direct physical and physiological meaning that reflects the force-generating
      capacity of the motor unit. Time-frequency analysis could also be used to study
      the specific frequency content of MUAPs and the energy of MUAPs within an
      interference pattern, without the need for decomposition.

PMID- 21903466
TI  - Simultaneous induction of calcium transients in embryoid bodies using
      microfabricated electrode substrates.
AB  - Precise control of differentiation processes of pluripotent stem cells is a key
      component for the further development of regenerative medicine. For this purpose,
      combining a cell-aggregate-size treatment for regulating intercellular signal
      transmissions and an electrical stimulation technique for inducing cellular
      responses is a promising approach. In the present study, we developed
      microfabricated electrode substrates that allow simultaneous stimulation of
      embryoid bodies (EBs) of P19 cells. Mouse embryonal carcinoma P19 cells can be
      induced to differentiate into three germ layers and serve as a promising stem
      cell model. Microcavity-array patterns were fabricated onto indium-tin-oxide
      (ITO) substrates using a standard photo-lithography technique, and uniform-sized
      EBs of P19 cells were inserted into each microcavity. Electrical stimulation was
      applied to the EBs through substrate electrodes and stimulus-induced
      intracellular calcium transients were monitored. We confirmed that the developed
      electrode device could simultaneously stimulate smaller (200MUm diameter) and
      larger (500MUm diameter) EBs inserted in the microcavities and induce specific
      spatio-temporal patterns of intracellular calcium transients in the EBs with fine
      reproducibility. We concluded that the developed microcavity array with embedded
      electrodes could simultaneously and effectively stimulate uniform-sized EBs
      inserted in it. Therefore, it is a promising experimental tool for precisely
      controlling cell differentiation processes.

PMID- 21903467
TI  - Artificial RNA aptamer production by the marine bacterium Rhodovulum
      sulfidophilum: improvement of the aptamer yield using a mutated transcriptional
      promoter.
AB  - Noncoding small RNAs and artificial RNA aptamers are now expected to be potential
      candidates for RNA therapeutic agents. We previously proposed a unique method for
      economical production of these RNAs using the marine phototrophic bacterium
      Rhodovulum sulfidophilum. This bacterium does not produce any ribonucleases but
      does produce extracellular nucleic acids in the culture medium in nature. Using
      this bacterium and an engineered plasmid containing the rrn promoter for the RNA
      expression, we developed a method for production of the streptavidin RNA aptamer
      in the culture medium. However, the yield of this RNA product in the culture
      medium by this method was not enough for practical use. In the present paper, we
      improved the yield of this product by modification of the -35 region of the rrn
      promoter so as to escape from the Fis protein control and the use of a new vector
      plasmid. Using this system, the extracellular RNA aptamer of approximately 200 ng
      and the total RNA aptamer (both extra- and intracellular form) of about 20 MUg
      from 1 L culture were accomplished by constitutive expression of the gene.

PMID- 21903468
TI  - Improving protein secretion of a transglutaminase-secreting Corynebacterium
      glutamicum recombinant strain on the basis of 13C metabolic flux analysis.
AB  - Corynebacterium glutamicum is known as a host species for amino acid production.
      This microorganism was recently noticed as a host that produces secreted
      proteins. In this study, we performed (13)C metabolic flux analysis ((13)C-MFA)
      on a recombinant C. glutamicum strain that secretes a heterologous
      transglutaminase (TGase) to improve TGase secretion. For the (13)C-MFA of a TGase
      secreting C. glutamicum strain in batch cultivation, a (13)C-labeling experiment
      and measurement of mass isotopomer distributions of proteinogenic amino acids
      were performed, and metabolic fluxes were determined considering the changes in
      fractional (13)C-labeling of proteinogenic amino acids with respect to culture
      time. The TGase yield increased at the stationary phase but decreased toward its
      end. The results of (13)C-MFA revealed that the flux from glycolysis to the TCA
      cycle gradually increased during TGase secretion. We speculate that the
      NADH/NAD(+) ratio in the cells increases and that as a result, the specific
      glucose uptake rate decreases in the stationary phase because of the increased
      flux of the TCA cycle. Since it is expected that a decrease in the NADH/NAD(+)
      ratio would improve the TGase yield, we tried to enhance lactate production in a
      TGase-secreting C. glutamicum strain to decrease cellular NADH levels by
      increasing the pH level in the culture. The TGase yield increased in 1.4-fold by
      increasing the pH from 6.7 to 7.2, indicating that the TGase yield was
      successfully improved on the basis of the (13)C-MFA.

PMID- 21903469
TI  - Isolation and characterization of a new dimeric esterase from Lactobacillus sakei
      23K.
AB  - The M(w) of a Lactobacillus sakei intracellular esterase, determined by gel
      filtration, was compared to those obtained from SDS-PAGE or MALDI-TOF, pointing
      to a dimeric structure. Its N-terminal sequence and peptide mass fingerprint
      suggest that it is the putative LSA044 protein from L. sakei 23K genome.

PMID- 21903470
TI  - Development of an efficient gene-targeting system in Aspergillus luchuensis by
      deletion of the non-homologous end joining system.
AB  - The industrial fungus Aspergillus luchuensis is used to produce a distilled
      spirit in Okinawa Island, Japan. Recently, the genome sequence of A. luchuensis
      RIB2604 (Aspergillus awamori NBRC 4314) was revealed and many functional genes
      are now expected to be analyzed. Gene targeting is necessary for analyzing the
      function of a gene; however, gene targeting frequencies in A. luchuensis are very
      low. To develop a highly efficient gene-targeting system for A. luchuensis, we
      disrupted A. luchuensis ligD (ALligD) encoding the human DNA ligase IV (ligIV)
      homologue using an Agrobacterium mediated gene transformation method. Deletion of
      ALligD dramatically improved homologous recombination efficiency (reached 100%)
      compared to that in the wild-type strain (0.8%), when 1000-bp homologous flanking
      regions were used. The ALligD disruptant showed no apparent defect in vegetative
      growth, and it exhibited increased sensitivity to phleomycin and high methyl
      methanesulphonate concentrations compared to the wild-type strain. Furthermore,
      using this ALligD disruptant, we disrupted ALpksP encoding an Aspergillus
      fumigatus polyketide synthase P (alb1/pksP) orthologue. The ALpksP disruptant
      displayed a decolourized conidial phenotype. This result indicated that ALpksP is
      a key factor for conidial black pigmentation in A. luchuensis. Our results
      indicate that the ALligD mutant is an efficient host for targeted gene disruption
      in A. luchuensis.

PMID- 21903471
TI  - Sequential chemotherapy for colorectal cancer.

PMID- 21903472
TI  - Implications of rarity of chromosome 17 polysomy in breast cancer.

PMID- 21903474
TI  - Update on antibacterial and antifungal drugs - can we master the resistance
      crisis?

PMID- 21903473
TI  - Sequential versus combination chemotherapy for the treatment of advanced
      colorectal cancer (FFCD 2000-05): an open-label, randomised, phase 3 trial.
AB  - BACKGROUND: The optimum use of cytotoxic drugs for advanced colorectal cancer has
      not been defined. Our aim was to investigate whether combination treatment is
      better than the sequential administration of the same drugs in patients with
      advanced colorectal cancer. METHODS: In this open-label, randomised, phase 3
      trial, we randomly assigned patients (1:1 ratio) with advanced, measurable, non
      resectable colorectal cancer and WHO performance status 0-2 to receive either
      first-line treatment with bolus (400 mg/m(2)) and infusional (2400 mg/m(2))
      fluorouracil plus leucovorin (400 mg/m(2)) (simplified LV5FU2 regimen), second
      line LV5FU2 plus oxaliplatin (100 mg/m(2)) (FOLFOX6), and third-line LV5FU2 plus
      irinotecan (180 mg/m(2)) (FOLFIRI) or first-line FOLFOX6 and second-line FOLFIRI.
      Chemotherapy was administered every 2 weeks. Randomisation was done centrally
      using minimisation (minimisation factors were WHO performance status, previous
      adjuvant chemotherapy, number of disease sites, and centre). The primary endpoint
      was progression-free survival after two lines of treatment. Analyses were by
      intention-to-treat. This trial is registered at ClinicalTrials.gov, NCT00126256.
      FINDINGS: 205 patients were randomly assigned to the sequential group and 205 to
      the combination group. 161 (79%) patients in the sequential group and 161 (79%)
      in the combination group died during the study. Median progression-free survival
      after two lines was 10.5 months (95% CI 9.6-11.5) in the sequential group and
      10.3 months (9.0-11.9) in the combination group (hazard ratio 0.95, 95% CI 0.77
      1.16; p=0.61). All six deaths caused by toxic effects of treatment occurred in
      the combination group. During first-line chemotherapy, significantly fewer severe
      (grade 3-4) haematological adverse events (12 events in 203 patients in
      sequential group vs 83 events in 203 patients in combination group; p<0.0001) and
      non-haematological adverse events (26 events vs 186 events; p<0.0001) occurred in
      the sequential group than in the combination group. INTERPRETATION: Upfront
      combination chemotherapy is more toxic and is not more effective than the
      sequential use of the same cytotoxic drugs in patients with advanced, non
      resectable colorectal cancer. FUNDING: Sanofi-Aventis France.

PMID- 21903475
TI  - Thrombotic thrombocytopenic purpura precipitated by acute pancreatitis.
AB  - A 20 year old woman, admitted with acute pancreatitis, subsequently developed
      microangiopathic haemolytic anaemia, thrombocytopenia and mild neurological
      compromise. A diagnosis of thrombotic thrombocytopenic purpura (TTP) was made,
      and she was treated with plasma exchange leading to complete resolution of this
      condition. TTP is a rare multisystem disorder which may be life threatening if
      not treated promptly. The increasing recognition of acute pancreatitis as a
      potential aetiological factor offers new insights into the pathogenesis,
      diagnosis and treatment of TTP.

PMID- 21903476
TI  - Analyses of data of patients with Thrombotic Microangiopathy in the WAA registry.
AB  - Thrombotic Microangiopathy (TMA) is a histopathological feature of various
      diseases including thrombotic thrombocytopenic purpura and hemolytic uremic
      syndrome. The aim of this study was to investigate the outcome and prognostic
      variables of TMA-patients. MATERIALS AND METHODS: Data were consecutively
      retrieved from the WAA-apheresis registry (www.waa-registry.org) during 2003
      2009. Included were all 120 patients (1237 procedures) who suffered from various
      forms of TMA, as registered by the ICD-10 code M31.1. Besides registry data, more
      extensive information was retrieved from the latest 64 patients. Adverse events
      of the TMA patients were compared to those of the other patients in the registry.
      RESULTS: The mean age was 46 years (range 11-85 years, 57% women). In 72%
      therapeutic apheresis was due to an acute indication while a long-term indication
      was present in 28%. Plasma exchange was performed by centrifugation and
      filtration technique (95% and 4%, respectively), and immunoadsorption in 1% of
      the patients. Only fresh frozen plasma was used as replacement fluid in 69% of
      procedures. Adverse events were more frequent than in the general apheresis
      population (10% versus 5%, RR 1.9, CI 1.6-2.3). No death occurred due to
      apheresis treatment. Three percent of the procedures were interrupted.
      Bronchospasm and/or anaphylactic shock were present in two patients and one
      patient suffered from TRALI. At admission 26% were bedridden and needed to be
      fed. The risk of dying during the treatment period was significantly higher if
      the patient also suffered from a compromising disease, such as cancer. There was
      an inverse correlation between the ADAMTS13 level and the antibody titer (r=
      0.47, p=0.034). CONCLUSIONS: Patients with TMA have an increased risk for
      moderate and severe AE compared to the general apheresis population. Many
      patients were severely ill at admission. The prognosis is worse if the patient
      also has a severe chronic disease. Even slightly increased ADAMTS13-antibody
      titers seem to have a negative impact on the ADAMTS13 levels.

PMID- 21903477
TI  - Suboccipital steroid injections for transitional treatment of patients with more
      than two cluster headache attacks per day: a randomised, double-blind, placebo
      controlled trial.
AB  - BACKGROUND: Suboccipital steroid injections can be used for preventive treatment
      of cluster headache but few data are available for the efficacy of this approach
      in clinical trials. We aimed to assess efficacy and safety of repeated
      suboccipital injections with cortivazol compared with placebo as add-on therapy
      in patients having frequent daily attacks. METHODS: In our randomised, double
      blind, placebo-controlled trial at the Emergency Headache Centre in Paris,
      France, we enrolled adults aged 18-65 years with more than two cluster headache
      attacks per day. We randomly allocated patients to receive three suboccipital
      injections (48-72 h apart) of cortivazol 3.75 mg or placebo, as add-on treatment
      to oral verapamil in patients with episodic cluster headache and as add-on
      prophylaxis for those with chronic cluster headache, on the basis of a computer
      generated list (blocks of four for each stratum). Injections were done by
      physicians who were aware of treatment allocation, but patients and the
      evaluating physician were masked to allocation. The primary outcome was reduction
      of the number of daily attacks to a mean of two or fewer in the 72 h period 2-4
      days after the third injection. We assessed all patients who received at least
      one dose of study drug in the intention-to-treat analysis. This study is
      registered with ClinicalTrials.gov, number NCT00804895. FINDINGS: Between
      November, 2008, and July, 2009, we randomly allocated 43 patients (15 with
      chronic and 28 with episodic cluster headache) to receive cortivazol or placebo.
      20 of 21 patients who received cortivazol had a mean of two or fewer daily
      attacks after injections compared with 12 of 22 controls (odds ratio 14.5, 95% CI
      1.8-116.9; p=0.012). Patients who received cortivazol also had fewer attacks
      (mean 10.6, 95% CI 1.4-19.9) in the first 15 days of study than did controls
      (30.3, 21.4-39.3; mean difference 19.7, 6.8-32.6; p=0.004). We noted no serious
      adverse events, and 32 (74%) of 43 patients had other adverse events (18 of 21
      patients who received cortivazol and 14 of 22 controls; p=0.162); the most common
      adverse events were injection-site neck pain and non-cluster headache.
      INTERPRETATION: Suboccipital cortivazol injections can relieve cluster headaches
      rapidly in patients having frequent daily attacks, irrespective of type (chronic
      or episodic). Safety and tolerability need to be confirmed in larger studies.
      FUNDING: None.

PMID- 21903478
TI  - Suboccipital steroid injections for cluster headache.

PMID- 21903479
TI  - A network of regulatory pathways in lepromatous leprosy.

PMID- 21903480
TI  - Blockade of the HER family of receptors in the treatment of HER2-positive
      metastatic breast cancer.
AB  - Breast cancer is the most common type of cancer among women and the second
      leading cause of cancer death in the United States. Metastatic breast cancer is
      considered incurable, and treatment is aimed at palliating symptoms, achieving
      remission, and prolonging survival. Treatment options for metastatic disease vary
      based on tumor surface markers and clinical factors in an individual patient and
      include cytotoxic chemotherapy, hormonal therapy, biological therapy, or some
      combination of these. An important molecular determinant of therapy is the human
      epidermal growth factor receptor 2 (HER2) positivity of the tumor, which affects
      response to HER2-targeted treatment. HER2 is a member of the human epidermal
      growth factor receptor family of receptor tyrosine kinases, also known as the HER
      family, which activates signaling that promotes tumorigenic cellular processes
      such as proliferation and evasion of apoptosis. Several targeted agents,
      including monoclonal antibodies and tyrosine kinase inhibitors that inhibit one
      or more HER family receptors have been developed that affect signaling through
      this pathway. Some of these, such as trastuzumab and lapatinib, have been
      approved for breast cancer treatment. Resistance to therapy is a challenge that
      limits the duration of benefit achieved with these agents. Therefore,
      combinations of HER family-targeted agents with other therapies such as cytotoxic
      agents, hormonal therapy, or inhibitors of other cellular pathways, are being
      developed to exploit synergy and overcome resistance mechanisms. Here we review
      the HER family-targeted agents currently approved or in development for HER2
      positive metastatic breast cancer with a focus on strategies to overcome tumor
      resistance.

PMID- 21903481
TI  - Menopausal state in breast cancer: how reliable is the data?
AB  - Despite the high importance of the menopausal state for the management of breast
      cancer, above all, when planning antihormonal adjuvant therapy, the menopausal
      state cannot be defined at the time of diagnosis ina significant proportion of
      women. The scope of uncertainties regarding the recording of the menopausal state
      in a cohort of patients with breast cancer is evaluated. INTRODUCTION: Menopause
      is a cornerstone both in breast cancer (BC) pathophysiology and in clinical
      management. The scope of uncertainties regarding the recording of the menopausal
      state in a cohort of patients with BC is evaluated in this study. PATIENTS AND
      METHODS: The data of a Swiss prospective relational BC database that covered a 20
      year period (1990-2009; n=1457) was analyzed. For the definition of menopause,
      the guidelines of the National Comprehensive Cancer Network were used. RESULTS:
      The menopausal state was unclear in 150 patients (10.2%). Of these, 122 (81.3%)
      had undergone a hysterectomy before menopause; in 28 women (18.7%), an endocrine
      therapy obscured the patient's actual endocrine status. When taking only the
      subgroup of women in which menopause usually occurs (45-55 years) into
      consideration, the menopausal state was unclear in 91 cases of 337 women (27.0%).
      From the entire cohort, the date of last menstruation remained obscure in 450
      patients (30.9%). CONCLUSION: Despite the high importance of the menopausal state
      for the management of BC, above all, when planning antihormonal adjuvant therapy,
      the menopausal state was unable to be defined at the time of BC diagnosis in a
      significant proportion of women. The dilemma that menopause cannot be assessed in
      some BC cases is increasingly being recognized. Close cooperation between
      oncologists and endocrinologists is desirable to establish an optimal,
      individually tailored therapy for women with an unclear menopausal state due to
      hormonal therapies, hysterectomy, or chemotherapy.

PMID- 21903482
TI  - Percutaneous placement of pedicle screws in overweight and obese patients.
AB  - BACKGROUND CONTEXT: In obese patients, placing pedicle screws percutaneously is a
      particular challenge. As the bulky and thick configuration of obese patients may
      produce fuzzier fluoroscopic view and longer passage of surgical instruments, the
      chances of misplacement might increase. PURPOSE: This study was designed to
      evaluate the effect of patient's body habitus on the incidence of percutaneous
      pedicle screw misplacements. STUDY DESIGN/SETTING: A retrospective study with
      prospectively collecting data. PATIENT SAMPLE: Three hundred seventy percutaneous
      pedicle screws for minimally invasive lumbar spinal fusion surgery were noted in
      89 consecutive patients. OUTCOME MEASURES: The position and direction of screws
      to pedicle were evaluated using the findings in computed tomography (CT) scan
      with the following grading method: Grade A, completely in the range without
      pedicle cortex violation; Grade B, pedicle wall violation <2 mm; Grade C, pedicle
      wall violation 2 to 4 mm; and Grade D, pedicle wall violation >4 mm. The
      direction of violation was grouped as medial, lateral, cranial, and caudal.
      METHODS: Two independent observers retrospectively examined all of the
      postoperative CT images. All screws were assigned into one of the following three
      groups along with patient's body mass index (BMI): 157 screws (38 patients) in
      normal weight (BMI<25) group; 124 (29) in overweight (25<=BMI<30) group; and 89
      (22) in obese (BMI>=30) group. A pedicle screw was considered misplaced if the
      grade was defined as B, C, and D. Multivariate logistic regression analyses were
      performed to evaluate the association between screw misplacements and BMI.
      RESULTS: Sixty-two screws (16.8%) were misplaced with the majority of Grade B
      (72.6%, 45/62) and lateral direction (72.6%, 45/62). Twenty-eight screws (22.6%,
      28/124) were misplaced in overweight group, 12 (13.5%, 12/89) in obese group, and
      22 (14.0%, 22/157) in normal weight group. Two symptomatic pedicle violations
      were noted with Grade D: a caudal violation was found in overweight group, which
      happened in the third case of surgeon's series; a medial misplacement, which was
      occurred in the 29th case, was noticed in obese group. There was no statistically
      significant association of pedicle violations along with patient's BMI (odds
      ratio [OR]=1.00, 95% confidence interval [CI]=0.94-1.07, p=.99). Moreover, no
      other factors, such as patient's age, gender, preoperative diagnosis, number of
      the fused segments, and year of the surgery, had a statistically significant
      relationship with pedicle violations. On the contrary, pedicle violations
      observed approximately five times more frequently at the level of L3 (47.1%,
      8/17) and L4 (28.8%, 36/125) rather than L5 (10.1%, 16/158) and S1 (2.9%, 2/70)
      (OR=4.95, 95% CI=2.62-9.33, p<.0001). CONCLUSIONS: Although symptomatic pedicle
      violations were noted in the earlier period of surgeon's learning curve and in
      overweight and obese patients, no statistical evidence could be found between
      patient's body habitus and percutaneous pedicle screw misplacement. Our data also
      suggest that greater caution should be exercised to avoid pedicle violations
      especially at L3 and L4.

PMID- 21903483
TI  - The relationship between psychological factors and performance on the Biering
      Sorensen back muscle endurance test.
AB  - BACKGROUND CONTEXT: Many studies report an association between low back pain
      (LBP) and reduced back muscle endurance and consider this to indicate muscular
      dysfunction. However, few have investigated the potentially confounding influence
      of psychological factors on performance during such endurance tests. PURPOSE:
      This study examined whether psychological factors were associated with
      "underperformance" on the Biering-Sorensen (BS) test (ie, not performing as well
      as one is physiologically capable of). STUDY DESIGN/SETTING: Cross-sectional
      study of the baseline data of patients with chronic (>3 months) nonspecific LBP
      (cLBP) before participation in a clinical trial of exercise therapy. PATIENT
      SAMPLE: One hundred forty-eight patients with cLBP (43% men; age, 45+/-10 years).
      OUTCOME MEASURES: The time for which the modified BS isometric endurance test
      could be performed to exhaustion minus the time that would have been predicted
      based on the rate of decline in median frequency of the surface electromyographic
      (EMG) signal recorded bilaterally from the erector spinae at L3 and L5. METHODS:
      Back pain and disability, psychological disturbance, catastrophizing, fear
      avoidance beliefs, back beliefs, and exercise self-efficacy were measured using
      validated questionnaires. Patients performed the BS test to exhaustion while
      physiological muscle fatigability was measured from continuous surface EMG
      recordings. RESULTS: Multivariable regression analysis controlling for gender
      revealed that greater psychological disturbance (p=.003) and more negative back
      beliefs (p=.015) were unique predictors of the extent of "underperformance,"
      accounting for 22.3% variance in expected endurance time minus actual time.
      CONCLUSIONS: It is important that the underlying nature (psychological or
      physiological) of performance deficits be identified during such tests because
      this may influence the interpretation of prospective studies reporting risk
      factors for LBP and dictate the particular treatment or interventional approach
      required to remedy the situation in individuals with LBP.

PMID- 21903484
TI  - Development of novel targeted agents in the treatment of metastatic colorectal
      cancer.
AB  - Colorectal cancer (CRC) remains the second most common cause of cancer death and
      third most common form of cancer in men and women. Although the incidence and
      mortality of CRC have been declining over the past 2 decades in the United
      States, nearly 140,000 new cases and 51,000 deaths were still estimated to occur
      in 2010.(1) These decreases have resulted primarily from earlier detection of
      premalignant colorectal polyps through CRC screening and to a lesser degree from
      adjuvant chemotherapy. Four cytotoxic chemotherapy drugs and 3 biologic agents
      have been approved by the US Food and Drug Administration (FDA) for CRC, but the
      contribution of each has been incremental and long-term survival of advanced
      disease remains poor. In addition, optimal populations for treatment with these
      agents remain to be fully characterized. Although the field of drug development
      in CRC was stagnant during a period of numerous large trials with approved
      agents, multiple new agents are currently in development. This review discusses
      molecular pathways and novel targeted agents in the treatment of CRC.

PMID- 21903485
TI  - Outcome of second-line treatment after first-line chemotherapy with the GONO
      FOLFOXIRI regimen.
AB  - PURPOSE: FOLFOXIRI demonstrated higher efficacy compared to 5-fluorouracil,
      leucovorin, irinotecan (FOLFIRI) as first-line treatment of metastatic colorectal
      cancer. We evaluated the outcome of second-line treatments among 196 patients
      treated with first-line FOLFOXIRI in three consecutive trials conducted by the
      Gruppo Oncologico Nord Ovest group. PATIENTS AND METHODS: One hundred seventy-two
      of 196 patients so far progressed and 136 (79%) received second-line therapies:
      32 (24%) were rechallenged with FOLFOXIRI, 52 (38%) were treated with irinotecan-
      or oxaliplatin-based doublets, and 52 (38%) received fluoropyrimidine plus
      mytomicin C or single-agent chemotherapy. Only 10 patients received bevacizumab
      (3) or cetuximab (7) with chemotherapy. Activity and efficacy data were collected
      and subgroup analyses were performed according to the regimen administered.
      RESULTS: Overall response rate (RR) was 23%; median progression-free survival
      (PFS) and overall survival (OS) were 5.9 and 13.2 months, respectively. At an
      exploratory subgroup analysis, retreatment with FOLFOXIRI was associated with
      longer PFS (8.2 versus 6.3 months; P = .003, hazard ratio [HR] = 0.61) and OS
      (19.3 versus 14.0 months; P = .02, HR = 0.57) compared with doublets; single
      agent chemotherapy or fluoropyrimidine plus mytomicin C was significantly lower
      in terms of RR (8%), PFS (3.0 months), and OS (8.7 months) compared with
      FOLFOXIRI or doublets. CONCLUSIONS: First-line FOLFOXIRI does not impair the
      efficacy of second-line treatments. In some patients rechallenge with FOLFOXIRI
      may represent a valid option, although potential imbalances in prognostic factors
      due to better patient selection should be considered.

PMID- 21903486
TI  - Reduction of treatment volume and radiation doses to surrounding tissues with
      intraprostatic gold markers in prostate cancer radiotherapy.
AB  - BACKGROUND: High-precision radiotherapy with gold marker implantation is a
      standard technique for prostate cancer treatment. To provide insight into the
      beneficial effect of gold markers, the influence on treatment volume and
      radiation doses to healthy tissues was investigated. PATIENTS AND METHODS: Three
      consecutive treatment margins were constructed, for 10 patients with localized
      prostate cancer, to show the reduction of planning target volume (PTV): PTV 10 mm
      (no markers), PTV 7 mm (markers), and PTV 7/5 mm (markers and online correction).
      On planning computed tomography (CT) scan, the prostate, bladder, rectal wall,
      and anal canal were contoured. The treatment volume and radiation doses to
      surrounding organs were calculated. In 65 patients, with the online protocol and
      gold markers, late toxicity was evaluated. RESULTS: With gold markers a
      significant PTV reduction of 27% was achieved (P < .001). Subsequently, radiation
      dose reductions to the mean of 17% (+/- 4.5%) to the bladder, 19% (+/- 4.7%) to
      the anal canal, and 12% (+/- 3%) to the rectal wall, respectively were seen (P <
      .001). With 5-mm posterior margins an additional PTV reduction of 3.7% (P < .001)
      and total radiation dose reduction to the mean of 24% (+/- 4%), and 16% (+/-
      4.5%) to anal canal and rectal wall, respectively were seen (P < .001). Late
      Grade 1-2 genitourinary and gastrointestinal toxicity was seen in 32%, and 33%,
      respectively. Grade 3 toxicity was less than 10%. CONCLUSIONS: This study showed
      a significant reduction of treatment volume and radiation doses to healthy
      tissues with intraprostatic gold markers.

PMID- 21903487
TI  - Novel conductometric biosensor based on three-enzyme system for selective
      determination of heavy metal ions.
AB  - A differential pair of planar thin-film interdigitated electrodes, deposited on a
      ceramic pad, was used as a conductometric transducer. The three-enzyme system
      (invertase, mutarotase, glucose oxidase), immobilized on the transducer surface,
      was used as a bioselective element. The ratio between enzymes in the membrane was
      found experimentally considering the highest biosensor sensitivity to substrate
      (sucrose) and heavy metal ions. Optimal concentration of sucrose for inhibitory
      analysis was 1.25 mM and incubation time in the investigated solution amounted to
      10-20 min. The developed biosensor demonstrated the best sensitivity toward ions
      Hg(2+) and Ag(+). A principal possibility of the biosensor reactivation either by
      EDTA solution after inhibition with silver ions or by cysteine solution after
      inhibition with mercury ions was shown.

PMID- 21903488
TI  - Simultaneous UFLC-ESI-MS/MS determination of piperine and piperlonguminine in rat
      plasma after oral administration of alkaloids from Piper longum L.: application
      to pharmacokinetic studies in rats.
AB  - The alkaloids from Piper longum L. showed protective effects on Parkinson's
      disease models in our previous study and piperine and piperlonguminine were the
      two main constituents in the alkaloids. The present study aimed at developing a
      rapid, sensitive, and accurate UFLC-ESI-MS/MS method and validating it for the
      simultaneous determination of piperine and piperlonguminine in rat plasma using
      terfenadine as the internal standard. The analytes and internal standard (IS)
      were extracted from rat plasma using a simple protein precipitation by adding
      methanol/acetonitrile (1:1, v/v). A Phenomenex Gemini 3 u C18 column (20 mm *
      2.00 mm, 3 MUm) was used to separate the analytes and IS using a gradient mode
      system with a mobile phase consisting of water with 0.1% formic acid (mobile
      phase A) and acetonitrile with 0.1% formic acid (mobile phase B) at a flow rate
      of 0.4 mL/min and an operating column temperature of 25 degrees C. The total
      analytical run time was 4 min. The detection was performed using the positive ion
      electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode with
      transitions at m/z 286.1-201.1 for piperine, m/z 274.0-201.1 for
      piperlonguminine, and m/z 472.4-436.4 for the IS. The calibration curves were
      both linear (r>0.995) over a concentration range of 1.0 to 1000 ng/mL; the lower
      limit of quantification (LLOQ) was 1.0 ng/mL for both piperine and
      piperlonguminine. The intra-day and inter-day precisions (RSD %) were <12.1%,
      accuracies ranged from 86.6 to 120%, and recoveries ranged from 90.4 to 108%. The
      analytes were proven stable in the short-term, long-term, and after three freeze
      thaw cycles. The method was successfully applied to pharmacokinetic studies of
      piperine and piperlonguminine in rats after oral administration of alkaloids from
      P. longum L.

PMID- 21903489
TI  - High-throughput comprehensive analysis of D- and L-amino acids using ultra-high
      performance liquid chromatography with a circular dichroism (CD) detector and its
      application to food samples.
AB  - A rapid and comprehensive analytical method for D- and L-enantiomers of
      proteinogenic amino acids was developed using ultra-high performance liquid
      chromatography (UHPLC) equipped with a circular dichroism (CD) detector. Pre
      column derivatization reagents were examined for enhanced sensitivity and
      selectivity for UV and CD detection: 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD
      F) was selected. The method, using a CD detector, does not require separation of
      optical isomers on a column to calculate the enantio ratio (%D) using the g
      factor value and produces a simple chromatogram in comparison to other reported
      methods. Using this advantage, combined with UHPLC technology, analysis time for
      the derivatized proteinogenic amino acids was within 5.5 min. The UV detection
      limit was 4.9-23 pmol/injection and the CD detection limit was 11-64
      pmol/injection. The method was applied to the analysis of D- and L-amino acids in
      food samples. D-Ala, D-Asp, D-Glu and D-Ser were detected at high concentrations
      in some Japanese black vinegars, fermented milks and yogurts. The results were
      identical to the results determined by the OPA method. We suggest the UHPLC-CD
      method would be useful in screening the D-amino acid content of foods and in
      helping to clarify the importance and reason for the presence of D-amino acids in
      foods.

PMID- 21903490
TI  - An LC-MS/MS assay to determine plasma pharmacokinetics of cyclic thymic
      hexapeptide (cTP6) in rhesus monkeys.
AB  - A robust and simple method for absolute quantification of a novel bidirectional
      immunomodulatory drug candidate, cyclic thymic hexapeptide (cTP6), in rhesus
      monkey plasma was developed and validated by liquid chromatography coupled with
      tandem mass spectrometry (LC-MS/MS). Plasma proteins were precipitated by adding
      four volumes of acetonitrile. Peptides in the supernatant were separated by
      liquid chromatography on an Agilent Zorbax Eclipse Plus-C18 chromatographic
      column with gradient elution using 0.1% formic acid in water (mobile phase A) and
      0.1% formic acid in methanol (mobile phase B) at 0.2 mL/min. The analytes were
      identified by triple quadrupole mass spectrometry in positive ion-mode. The assay
      was linear over a concentration range of 10-5000 ng/mL for cTP6, with a lower
      limit of quantification (LLOQ) of 10 ng/mL. Intra- and inter-day precision of the
      assay at three concentrations were 1.51-7.70% with accuracy of 95.1-104.2%. The
      average recovery of cTP6 for three concentration levels was 59.6-64.0%. No
      significant matrix effect was observed. Peptide cTP6 was detected in plasma of
      live rhesus monkeys up to 6-8h after intra-muscular injection. The half-life was
      2.24-2.95 h. The result revealed a nonlinear pharmacokinetic response to
      increasing doses of cTP6 (100, 200, 500 MUg/kg). For the multiple dose study of
      cTP6, the drug did not accumulate during daily administration at 100 MUg/kg for 7
      consecutive days in rhesus monkeys.

PMID- 21903491
TI  - [The Spanish Paediatric Association ethical framework: a commitment to the ethics
      of organizations].

PMID- 21903492
TI  - Perinatal infection, inflammation, and retinopathy of prematurity.
AB  - The major known risk factors for retinopathy of prematurity (ROP) are extremely
      low gestational age, exposure to high levels of oxygen early after birth (phase
      I) and relatively lower oxygen levels later (phase II). In this review, we
      summarize recent data suggesting that exposure to perinatal
      infection/inflammation is associated with an increased risk for ROP. Part of this
      effect might be due to direct exposure of the developing retina to circulating
      products of infection and/or inflammation. Another potential mechanism that
      deserves exploration is that inflammation and/or oxidative stress can modify the
      known increased risk of oxygen-associated ROP. Taken together, accumulating
      evidence suggests that prenatal, perinatal, and postnatal systemic inflammation
      contribute to a 'pre-phase', sensitizing the pre-ROP retina for subsequent
      insults, setting the stage for what are now called phase I and phase II of ROP
      pathogenesis. Strategies targeting inflammatory responses might help reduce the
      risk for ROP in extremely low gestational age newborns.

PMID- 21903493
TI  - A prospective study on non-surgical correction of protruding ears: the importance
      of early treatment.
AB  - OBJECTIVES: Splinting is an elegant method to correct ear deformities in the
      newborn. However evidence is lacking on the relation between age and efficacy and
      duration of the treatment. We prospectively studied these questions on protruding
      ears in 132 babies. METHODS: A splint in the scaphal hollow was used in
      combination with tape (Earbuddies((r))). Treatment continued until the desired
      shape persisted. Results were judged from photographs and mastoid-helical
      distance was measured. RESULTS: In 132 babies 209 ears were treated. Twenty-four
      patients had no follow-up, 27 stopped therapy for skin irritation and fixation
      problems. In the remaining patients results were good in 28%, fair in 36%, poor
      in 36%. Efficacy deteriorates with age; with fair or good results in 66.7% if
      therapy started before the sixth week. Older children needed to be splinted
      longer. The anti-helical fold was easier corrected than a deep concha (correction
      in 69.8% versus 26.8%). CONCLUSIONS: Considering splinting therapy for protruding
      ears, a reasonable chance of success can only be offered to parents of children
      up to six weeks of age. It is favorable if the deformity is mainly due to a flat
      antihelix.

PMID- 21903494
TI  - Effect of eliminating the residual fluoride gel on titanium bracket corrosion.
AB  - INTRODUCTION: Fluoride ions, in long-term applications on titanium brackets,
      cause their corrosion. Fluoride gel used for caries prevention during orthodontic
      treatment has a very high concentration in fluoride ions, and therefore has the
      potential for causing bracket corrosion. The main aim of this study was to
      determine the effect of eliminating the residual fluoride gel, by rinsing it, on
      the corrosion of titanium brackets. The secondary aim was to evaluate the
      corrosion of titanium brackets in the presence of fluoride gel. METHODS: One
      hundred titanium brackets were divided into five groups of 20 brackets each.
      Group 1 being the control group, the rest of the groups were immersed in fluoride
      gel: Group 2 for 4 minutes and kept for 30 minutes with the residual fluoride gel
      on; Group 3 for 4 minutes followed by immediate water rinsing; Group 4 for 12
      minutes and kept for 90 minutes with the residual fluoride gel on and Group 5 for
      12 minutes followed by immediate water rinsing. All groups were rinsed then
      dried, for 20 hours, using Silica gel in a desiccator maintained at 37 degrees C
      before testing. RESULTS: Gravimetrical results and SEM analysis showed no
      significant difference between Groups 2, 3 and 5 compared to each other and to
      the control group. Only Group 4 showed significant weight loss and pitting
      corrosion in four of the 20 brackets. In sliding resistance, no significant
      difference was detected between any of the groups. CONCLUSIONS: Short time
      applications of fluoride gel do not affect sliding resistance of titanium
      brackets. No titanium corrosion was detected for one application of concentrated
      fluoride gel and some brackets showed pitting corrosion for three applications.
      The rinsing of residual fluoride gel eliminates completely the risk of bracket
      corrosion.

PMID- 21903496
TI  - Women's perceptions of their healthcare experience when they choose not to
      breastfeed.
AB  - RESEARCH QUESTION: How do women who choose not to breastfeed perceive their
      healthcare experience? METHOD: This qualitative research study used a
      phenomenographic approach to explore the healthcare experience of women who do
      not breastfeed. Seven women were interviewed about their healthcare experience
      relating to their choice of feeding, approximately 4 weeks after giving birth.
      Six conceptions were identified and an outcome space was developed to demonstrate
      the relationships and meaning of the conceptions in a visual format. FINDINGS:
      There were five unmet needs identified by the participants during this study.
      These needs included equity, self sufficiency, support, education and the need
      not to feel pressured. CONCLUSION: Women in this study who chose not to
      breastfeed identified important areas where they felt that their needs were not
      met. In keeping with the Code of Ethics for Nurses and Midwives, the identified
      needs of women who do not breastfeed must be addressed in a caring, compassionate
      and just manner. The care and education of women who formula feed should be of
      the highest standard possible, even if the choice not to breastfeed is not the
      preferred choice of healthcare professionals.

PMID- 21903497
TI  - Typing of 30 insertion/deletions in Danes using the first commercial indel kit-
      Mentype(r) DIPplex.
AB  - In this study, we tested the first commercial kit with insertion/deletion (indel)
      polymorphisms, the Mentype((r)) DIPplex PCR Amplification Kit (DIPplex kit). A
      total of 30 biallelic autosomal indels and Amelogenin were amplified with the
      DIPplex kit. All loci were amplified in one PCR multiplex and all amplicon
      lengths were shorter than 160 bp. Full indel profiles were generated from as
      little as 100 pg of DNA. A total of 117 individuals from Danish paternity cases
      were successfully typed. No deviation from Hardy-Weinberg equilibrium was
      observed for any of the indels. The combined mean match probability was 3.3 * 10(
      13), the mean paternity exclusion probability was 99.7% and the typical paternity
      indices for trios and duos were 2350 and 165, respectively. Furthermore, we typed
      five highly degraded DNA samples with the DIPplex kit, the AmpFlSTR((r)) SGM Plus
      kit and the AmpFlSTR((r)) SEfiler Plus kit. Full indel profiles were obtained
      with the DIPplex kit, whereas only partial profiles were obtained with the STR
      kits. In general, the DIPplex kit performed well and it would be a valuable assay
      for forensic genetic testing, especially in crime cases with partially degraded
      DNA or low amounts of template DNA. However, some difficulties with pull-ups were
      observed at DNA concentrations of 1000 pg. Rearrangement of the allele windows by
      changing the lengths of some of the PCR primers would greatly improve the assay,
      and more robustness towards higher amounts of DNA would allow the use of the
      DIPplex kit without prior quantification of the samples.

PMID- 21903498
TI  - A model for data analysis of microRNA expression in forensic body fluid
      identification.
AB  - MicroRNAs (miRNAs, 18-25 bases in length) are small, non-coding RNAs that
      regulate gene expression at the post-transcriptional level. MiRNA expression
      patterns, including presence and relative abundance of particular miRNA species,
      provide cell- and tissue-specific information that can be used for body fluid
      identification. Recently, two published studies reported that a number of body
      fluid-specific miRNAs had been identified. However, the results were inconsistent
      when different technology platforms and statistical methods were applied. To
      further study the role of miRNAs in identification of body fluids, this study
      sets out to develop an accurate and reliable model for data analysis of miRNA
      expression. To that end, the relative expression levels of three miRNAs were
      studied using the mirVanaTM miRNA Isolation Kit, high-specificity stem-loop
      reverse transcription (RT) and high-sensitivity hydrolysis probes (TaqMan)
      quantitative real-time polymerase chain reaction (qPCR) in forensically relevant
      biological fluids, including venous blood, vaginal secretions, menstrual blood,
      semen and saliva. Accurate quantification of miRNAs requires not only a highly
      sensitive and specific detection platform for experiment operation, but also a
      reproducible methodology with an adequate model for data analysis. In our study,
      the efficiency-calibrated model that incorporated the impact of the
      quantification cycle (Cq) values and PCR efficiencies of target and reference
      genes was developed to calculate the relative expression ratio of miRNAs in
      forensically relevant body fluids. Our results showed that venous blood was
      distinguished from other body fluids according to the relative expression ratio
      of miR16 using as little as 50pg of total RNA, while the expression level of
      miR658 was unstable and that of miR205 was nonspecific among different body
      fluids. Collectively, the findings may constitute a basis for future miRNA-based
      research on body fluid identification and show miRNAs as a promising biomarker in
      forensic identification of body fluids.

PMID- 21903499
TI  - Residual inferior glenohumeral instability after arthroscopic Bankart repair:
      radiological evaluation and functional results.
AB  - INTRODUCTION: Treatment of anteroinferior shoulder instability by arthroscopy
      must restore stability while preserving joint motion. Inferior glenohumeral
      ligament (IGHL) laxity is an important parameter in the pathomechanism of this
      condition. The goals of this study is to use the Shoulder HyperAbduction Test
      (SHART) radiological test to quantify the tension in the IGHL following surgery
      and look for an eventual correlation between ligament tightening and joint
      motion. METHODS: This was a single-center, retrospective study that included
      patients with unilateral anteroinferior instability who were treated with an
      arthroscopic Bankart repair between September 2004 and December 2005. These
      patients did not experience any recurrence within a follow-up period of at least
      2 years. Twenty-three patients were followed-up. This series included 16 men and
      seven women with an average age of 29.7+/-12 years. The average Instability
      Severity Index Score (ISIS) was 1.7+/-1.3 (from 0 to 3). The main outcome
      measures were the bilateral SHART test at the last follow-up visit and bilateral
      joint range of motion, before surgery and at the last follow-up. RESULTS: The
      follow-up was 3.3 years on average. The average SHART on the operated side
      (116.9+/-11.7 degrees ) was lower than the healthy side (121.9+/-9.6 degrees ),
      P=0.01. A difference of less than 4 degrees  was statistically related to loss of
      external rotation, with an odds ratio of 16, P=0.03. At the last follow-up, the
      average Walch-Duplay functional score was 72.4+/-13.8/100 and the Rowe score
      90.2+/-11.6/100. DISCUSSION: It is difficult to achieve a perfect compromise
      between shoulder stability and joint motion. Progress in arthroscopy technique
      has led to a greater demand for the tightening of capsulo-labral and ligament
      structures. An arthroscopic Bankart repair provides IGHL tightening that is
      quantifiable with the SHART. External rotation is reduced when excessive
      tightening is made.

PMID- 21903500
TI  - Trochanteric locking nail versus arthroplasty in unstable intertrochanteric
      fracture in patients aged over 75 years.
AB  - INTRODUCTION: In trochanteric fracture, whatever its anatomic type, internal
      fixation is currently the standard attitude, with arthroplasty as a relatively
      unusual option. HYPOTHESIS: Hip implants are an excellent alternative to
      osteosynthesis in unstable trochanteric fracture in patients aged over 75 years.
      PATIENTS AND METHODS: A non-randomised prospective multicenter study compared
      osteosynthesis by trochanteric nailing (n=113) to hip arthroplasty (n=134) in
      unstable trochanteric fracture (AO types 31 A2.2 and 3 and A3.3) in 247 patients
      over the age of 75 years. The series was recruited during 2007 in seven centres,
      four of which included only arthroplasties, two only osteosyntheses and one both.
      The two groups were comparable in age, sex, preoperative Parker score, pre
      fracture place of residence, fracture type, time to surgery and preoperative
      comorbidity. The sole difference was in operators, with more senior surgeons in
      arthroplasty (62% versus 27%). RESULTS: Three-month mortality was identical in
      the two groups (21.2% versus 21%). General complications did not differ, although
      mechanical complications were more frequent in the nailing group (12.5% versus
      2.8%). Functional results (Parker and PMA scores) were better in the implant than
      in the nail group. DISCUSSION: The present study validated hip arthroplasty in
      these indications. Cemented stems associated to a dual-mobility acetabular
      component gave the best results. TYPE OF STUDY: Prospective, level of evidence
      III.

PMID- 21903501
TI  - Morphometric analysis and functional correlation of tibial and femoral footprints
      in anatomical and single bundle reconstructions of the anterior cruciate ligament
      of the knee.
AB  - INTRODUCTION: The anterior cruciate ligament (ACL) is composed of an infinite
      number of fibers whose individual anatomical and biomechanical features have been
      well defined. Although numerous biomechanical studies have shown that
      reconstruction that is as anatomical as possible results in better control of
      rotational laxity, very few studies have investigated the surface area of tibial
      and femoral insertion sites in these reconstructions. The aim of this study was
      to compare the surface areas of tibial and femoral insertion sites in single and
      double bundle reconstructions and correlate these findings with the isometry
      profile obtained. Our hypothesis was that double bundle (DB) reconstruction
      results in better filling of the native ACL footprint thus increasing the
      biomechanical value of available graft tissue. PATIENTS AND METHODS: Forty-six
      patients underwent computer navigated ACL using hamstring tendons: 23 underwent
      single bundle (SB) and 23 DB reconstruction. The Praxim navigation station
      equipped with ACL logics software made it possible to digitize insertion site
      footprints, register perioperative data for graft position as well as
      anteroposterior and rotational laxities and pivot shift. RESULTS: There was a
      statistically significant difference between the two groups for tibial and
      femoral insertion site surface areas: 71 mm(2) +/- 17 (SB) versus 99.9 mm(2) +/-
      30 (DB) for the tibia, 67 +/- 11 mm(2) (SB) versus 96.9 mm(2) +/- 28 (DB) for the
      femur. Isometry profiles showed that anisometry was favorable in all cases: 2.5
      mm +/- 2 for SB; 2.9 mm +/- 2 for the anteromedial bundle (AMB) with DB and 9.6
      mm +/- 3.7 for the posterolateral bundle. When both groups were combined, there
      was a statistically significant correlation between the size of tibial insertion
      surface area and anteroposterior and rotational laxity. DISCUSSION: This study
      confirms that better filling of native ACL footprint surface areas results in
      better control of anteroposterior laxity. LEVEL OF EVIDENCE: Level IV.

PMID- 21903502
TI  - Evaluation under real-life conditions of a stand-alone fall detector for the
      elderly subjects.
AB  - BACKGROUND AND OBJECTIVES: Elderly patients unable to get up after a fall or to
      activate an alarm mechanism are particularly at risk of complications and need to
      be monitored with extreme care. The different risk factors have fostered the
      development of stand-alone devices facilitating early detection of falls. We
      aimed at assessing performance of the Vigi'Fall((r)) system, a cutting edge fall
      detector associating a "passive release" mechanism attached to the patient and
      including external sensors; in the event of a fall, the system automatically
      triggers an alarm, and it also incorporates embedded confirmation software. We
      have put it to the test under real-life conditions so as to evaluate not only its
      efficacy, but also and more particularly its acceptability and tolerability in
      elderly subjects. METHOD: The study ran from March 2007 through December 2008 in
      a geriatric ward with 10 subjects over 75 years of age, all of whom presented
      with a risk of falling. RESULTS: For eight patients wearing an accelerometric
      sensor, eight "falling" events and 30 "alarm release" events were recorded.
      Sensitivity and specificity of the device came to 62.5 and 99.5% respectively.
      For the two patients wearing the complete device, no events were detected. Not a
      single adverse occurrence was noted. Local tolerance was excellent in all but one
      of the subjects. CONCLUSION: Our results clearly show that the device may be worn
      by patients without discomfort over prolonged periods of time, and also
      demonstrate that the verification component will help to increase sensitivity in
      real-life conditions to a level comparable to the level attained in our
      laboratory studies.

PMID- 21903503
TI  - Risk-adjusted female breast cancer incidence rates in the United States.
AB  - A method has been previously proposed for estimating risk-adjusted incidence
      rates (RAIRs) from cancer data from the Surveillance, Epidemiology, and End
      Results (SEER) program. Unlike conventionally reported SEER-based cancer
      incidence rates in the United States, but similar to the approach taken by the
      International Association of Cancer Registries and the International Agency for
      Research on Cancer, the method uses only the first primary cancer of the given
      site. In addition, it also adjusts for population-based cancer prevalence in
      order to obtain a better population-based measure of cancer risk. For most
      cancers multiple cancer primaries are rare and the prevalence of the disease is
      low. However, female breast cancer has a comparatively high risk of subsequent
      breast cancers and is the most prevalent cancer in women. Hence, in white women
      RAIRs are 3.0% lower in ages 30-39, 4.2% lower in ages 40-49, 4.0% lower in ages
      50-59, 4.1% lower in ages 60-69, 3.8% lower in ages 70-79, and 4.3% lower in ages
      80 years and older compared with conventional rates. Corresponding lower
      percentages for black women are 3.9%, 6.9%, 5.1%, 7.8%, 6.0%, and 2.2%,
      respectively. Age-group specific trends in breast cancer incidence rates differed
      between RAIRs and conventional incidence rates, increasingly so with older age.
      The number of cancer cases in the United States is estimated from conventional
      incidence rates and population estimates. In 2007, the estimated number of
      malignant breast cancer cases was 181,665 for white women and 20,203 for black
      women. The estimated number of breast cancer cases decreased by 4.8% for whites
      and 6.5% for blacks when based on RAIRs. RAIRs are a better measure of breast
      cancer risk and trends in RAIRs are better for monitoring the effect of risk
      factors.

PMID- 21903505
TI  - Idioventricular rhythm in a patient with acute cholecystitis.

PMID- 21903504
TI  - Increased serum lactate dehydrongenase should be included among the variables
      that define very-high-risk multiple myeloma.
AB  - BACKGROUND: In patients who have symptomatic multiple myeloma (MM), a high serum
      lactate dehydrogenase (LDH) level is associated with features of advanced
      disease, adds prognostic value to the international staging system (ISS) and
      predicts for inferior survival. However, it has not been clearly defined what the
      impact of this abnormality is for patients treated upfront with novel agent-based
      regimens. PATIENTS AND METHODS: To address this issue we analyzed 203 consecutive
      unselected patients with symptomatic MM who received upfront treatment with novel
      agents in a single center. RESULTS: The median overall survival for patients with
      normal LDH was 54 months but in patients with increased LDH levels it was 21
      months (P = .003), whereas increased serum LDH was associated with a higher
      probability of early death. Multivariate analysis confirmed that an increased LDH
      level is independently associated with poor survival. Furthermore, increased LDH
      levels could identify subgroups of patients within ISS-2 and ISS-3 with even
      worse outcome. CONCLUSION: We conclude that serum LDH is a simple, inexpensive,
      and readily available blood test that may be included among the variables that
      define very-high-risk MM.

PMID- 21903506
TI  - [Immunoglobulin A nephropaty: clinical practice guidelines].
AB  - Immunoglobulin A nephropathy (N.IgA) is the world most common glomerular disease;
      15-50% of patients develop loss of renal function in 10-20 years, and the rest
      remission or mild proteinuria/ hematuria. The optimal treatment is uncertain. Our
      aim was to develop evidence-based recommendations through research in Medline,
      Embasse, Lilacs and Cochrane Central Register of Controlled Trials. The study
      quality was independently assessed by the reviewers following the Cochrane Renal
      Group checklist: randomization, blinding, intention-to-treat analysis and follow
      up period. Levels of evidence and grades of recommendation were assigned
      according to Center for Evidence-Based Medicine, Oxford. Two approaches were
      considered: Immunosuppressive therapy (corticosteroids, cytostatics, cyclosporine
      A, mycophenolate-mofetil): Level I a, grade A. -Combined suppressive therapy in
      adults. Corticosteroids plus cytotoxics drugs (cyclophosphamide/azathioprine):
      Level II b, grade B. In children with severe IgA nephropathy: Level II b, grade
      D. Cyclosporine and mycophenolate- mophetil: Level II b, grade C. Cyclosporine
      and mycophenolate-mophetil: Level ll b, grade C. -Non immunosuppressive therapy:
      reninangiotensin converting enzyme inhibitors (ACEI) and/or angiotensin II
      receptor blockers (ARB), fish oil, statins, antiplatelets and tonsillectomy. ACEI
      and/or ARB, in patients with proteinuria >= 1 g: Level I a, grade A. In children
      with moderate proteinuria: ACEI and/or ARB with close monitoring of renal
      function and serum potassium level: Level II b, grade B. Antiplatelet as
      supportive treatment: Level I a, grade C. Fish oil in addition to ACEI or ARB in
      patients with mild histological lesions: Level II b, grade B (Not in children).
      Statins: no evidence to recommend these drugs in children. In patients > 5 years
      with nephrotic syndrome and hyper-cholesterolemia, use statins with close
      monitoring of serum creatine-kinase. There is no evidence to recommend
      tonsillectomy.

PMID- 21903507
TI  - Management of the severely worn dentition with different prosthetic
      rehabilitation methods: a case series.
AB  - Clinicians are often faced with the challenge of restoring a severely worn
      dentition. Esthetic and functional rehabilitation of patients in this condition
      represents a noteworthy clinical challenge. Although treatment options for the
      severely worn dentition with reduced occlusal vertical dimension can be limited,
      providing a functional and esthetic restoration in these situations is crucial
      for restoring the patient's quality of life. Different treatment approaches for
      the rehabilitation of worn dentition are presented in this case series.

PMID- 21903508
TI  - Opiate overdose in an adolescent after a dental procedure: a case report.
AB  - Oxycodone/acetaminophen is a combination of acetaminophen and the opiate
      oxycodone. It is an effective analgesic that is commonly prescribed
      postoperatively. The potential for misuse, diversion, abuse, and overdose with
      opiates in general is an area of increasing concern to all prescribing
      clinicians. This case report illustrates the possibility of a severe or
      potentially fatal outcome to a common prescribing practice. Caution is emphasized
      when prescribing opiates, and screening for substance misuse and suicide risk
      factors is recommended.

PMID- 21903509
TI  - Gradual surface degradation of restorative materials by acidic agents.
AB  - The aim of this study was to investigate the effect of acidic agents on surface
      roughness and characteristics of four restorative materials. Fifty-two discs were
      created from each restorative material: metal-reinforced glass ionomer cement
      (Ketac-S), resin-modified glass ionomer cement (Fuji II LC), resin composite
      (Filtek Z250), and amalgam (Valiant-PhD); each disc was 12 mm in diameter and 2.5
      mm thick. The specimens were divided into four subgroups (n=13) and immersed for
      168 hours in four storage media: deionized water (control); citrate buffer
      solution; green mango juice; and pineapple juice. Surface roughness measurements
      were performed with a profilometer, both before and after storage media
      immersion. Surface characteristics were examined using scanning electron
      microscopy (SEM). Statistical significance among each group was analyzed using
      two-way repeated ANOVA and Tukey's tests. Ketac-S demonstrated the highest
      roughness changes after immersion in acidic agents (p<0.05), followed by Fuji II
      LC. Valiant-PhD and Filtek Z250 illustrated some minor changes over 168 hours.
      The mango juice produced the greatest degradation effect of all materials tested
      (p<0.05). SEM photographs demonstrated gradual surface changes of all materials
      tested after immersions. Of the materials evaluated, amalgam and resin composite
      may be the most suitable for restorations for patients with tooth surface loss.

PMID- 21903510
TI  - Cast metal bases as an economical alternative for the severely resorbed mandible.
AB  - Resorption of the alveolar ridge is a common problem in edentulous patients and
      can compromise the stability and function of dentures. Resorption and its
      consequences can be minimized when strategically placed implants are used;
      however, this option is financially out of reach for many patients. The article
      discusses a more cost-effective alternative (metalbased dentures) for patients
      with ridge resorption. In certain environments, like a dental school, where
      patients are looking for solutions to their dental problems at a reasonable
      price, cast metal bases can be a feasible economical alternative for edentulous
      patients. Both cases presented here demonstrated a significant improvement in
      stability, phonation, and mastication.

PMID- 21903511
TI  - Effect of fiber posts with different emerging diameters on the fracture strength
      of restored crownless teeth.
AB  - The relatively low elastic modulus of fiber posts reduces the risk of root
      fracture, but it also decreases composite core stabilization. To compensate for
      the lack of rigidity, larger post sizes can be necessary when restoring crownless
      teeth that have significant internal destruction of the root canal. This study
      evaluated the effectiveness of fiber posts with different emerging diameters and
      shapes on composite core stabilization as measured by fracture strength testing.
      Fracture strengths ranged from 262.6 +/- 81 N to 422.8 +/- 56 N. A one-way ANOVA
      test showed that fracture strength was affected by type of post (p<0.0001);
      single-tapered posts were weaker than double-tapered posts. Pearson's linear
      correlation test showed that the fracture strength results appear to have a
      direct correlation to the emerging diameter of the post (p<0.0001; r(2)=0.6191).
      The emerging diameter of fiber posts is important to stabilize the core. When
      restoring crownless teeth, it is advisable to use fiber posts with large emerging
      diameters; no additional preparation of the internal root dentin is necessary to
      enlarge the post diameter.

PMID- 21903512
TI  - Using cone beam computed tomography to determine safe regions for implant
      placement.
AB  - This study sought to identify and follow the course of the incisive canal in the
      mental interforaminal region of the human mandible and to describe other
      anatomical landmarks present in this region. Cone beam computerized tomography
      (CBCT) studies for 40 patients were collected from the database at the Department
      of Oral & Maxillofacial Radiology, School of Dentistry, Lebanese University. Ten
      patients had edentulous mandibles; the other 30 had partially or completely
      dentate mandibles. Axial native images and panoramic and cross-sectional
      reconstructions were examined to assess the anatomical landmarks in the anterior
      mandible. Multiple neurovascular canals and foramina were clearly detected on
      CBCT studies of the mandible. Numerous foramina were seen on the internal surface
      of the mandible, even distant from the midline. The incisive canal was identified
      in 97.5% of the images. These anatomical landmarks should be evaluated carefully
      during preoperative planning.

PMID- 21903513
TI  - Recurrence of central odontogenic fibroma: a rare case.
AB  - Central odontogenic fibroma (COF) is a rare, benign, painless, slow-growing tumor
      associated with expansion of the bone cortex. Histologically, it consists of
      fibrous connective tissue that contains multiple islands of odontogenic
      epithelium. Some lesions have diffuse spherical calcifications that usually are
      related to islands or cords of epithelium. The majority of cases respond well to
      conservative treatment such as enucleation and the prognosis is favorable;
      recurrences are rare. This article presents a rare case of COF that was located
      in the anterior region of the maxilla and treated with enucleation; the case
      recurred five years following the initial treatment.

PMID- 21903514
TI  - Flexural bond strength of repaired composite resin restorations: influence of
      surface treatments and aging.
AB  - The objective of this study was to evaluate the effect of storage in deionized
      water at room temperature, for seven days and six months, on the flexural
      strength of a repaired photocured microhybrid composite resin, using different
      surface treatments. After each surface treatment, the adhesive interface was
      analyzed with a surface roughness tester. The flexural strength of samples from
      each group was determined by three-point bending in a testing machine at a
      crosshead speed of 0.5 mm/min with a 50 N load cell. Data were analyzed using
      ANOVA (p=0.0001) and compared with the Newman-Keuls multiple comparison test. It
      was verified that flexural strength of the unrepaired specimens, after both seven
      days and six months, was similar (p>0.05) and was in accordance with ISO
      specifications (minimum of 50 MPa), with values ranging from 52-63 MPa. The
      authors concluded that the use of an unfilled resin agent is necessary prior to
      the repair to increase the adhesive strength. Further, the use of a silane agent
      prior to use of the unfilled resin agent is unnecessary, since it does not
      increase the adhesive strength.

PMID- 21903515
TI  - Follow the money.

PMID- 21903516
TI  - Botulinum toxin (Botox, Dysport, and Myobloc): pharmacology 101.

PMID- 21903517
TI  - Pre-prosthetic orthodontics for esthetics and function in restorative dentistry.

PMID- 21903518
TI  - Latest innovations in flowable composites.

PMID- 21903519
TI  - Evaluation of the microbial flora found in woodwind and brass instruments and
      their potential to transmit diseases.
AB  - Previous studies of dental devices (toothbrushes, dentures, and protective
      athletic mouthguards) have demonstrated microbial contamination of these devices
      and possible transmission of infectious diseases to the users. Since woodwind and
      brass instruments come into intimate contact with the musician's oral cavity and
      often are passed from student to student without sanitization, the question
      arises as to whether these instruments are contaminated and can transmit
      microbial diseases. The purpose of this study was to determine if woodwind and
      brass instruments and/or their cases harbor opportunistic, pathogenic, or
      allergenic microorganisms that can be transmitted to the musician. The internal
      components of woodwind and brass instruments harbored opportunistic, pathogenic,
      and/or allergenic microorganisms. The highest concentrations of microorganisms
      were found consistently at the mouthpiece end, but there was evidence of
      contamination throughout the instruments and their cases. The close proximity of
      contaminated mouthpieces to the oral cavity could facilitate local and systemic
      dissemination of the resident opportunistic, pathogenic, and/or allergenic
      microorganisms. General dentists should determine whether patients play a brass
      or woodwind instrument and be aware of the possible impact of this activity on
      the oral cavity and the entire body.

PMID- 21903520
TI  - What every dentist should know about zinc.
AB  - Zinc plays an important role in human physiology, from its involvement in the
      proper function of the immune system to its role in cellular growth, cell
      proliferation, and cell apoptosis as well as its essential role in the activity
      of numerous zinc-binding proteins. However, zinc also plays a key
      pathophysiological role in major neurological disorders and diabetes. Zinc
      deficiency is a worldwide problem, whereas excessive intake of zinc is relatively
      rare. Many patients are exposed to zinc on a regular basis through dentistry as a
      result of its use in certain restorative materials, mouthwashes, toothpastes and,
      notably, denture adhesives. Of particular importance to dental professionals are
      various case reports concerning the neurologic effects of excess zinc intake by
      patients who routinely use large quantities of zinc-containing denture adhesives.
      This review presents relevant information concerning the use of zinc in
      dentistry.

PMID- 21903521
TI  - Dentin hypersensitivity and its management.
AB  - Dentin hypersensitivity is a common patient complaint that is more prevalent than
      the profession realizes. It is important for dentists to diagnose dentin
      hypersensitivity by exclusion and provide appropriate treatment recommendations
      for patients. Various treatment methods have been proposed but no universally
      accepted desensitizing agent or treatment has been identified. When a patient has
      symptoms that can be attributed to dentin hypersensitivity, a thorough clinical
      examination should be carried out to rule out other likely causes prior to
      diagnosis and treatment. Depending on the identified cause, a combination of
      individualized instructions on proper oral health behaviors, use of at-home
      products, and professional treatment may be required to manage the problem.

PMID- 21903523
TI  - Incomplete cusp fractures: early diagnosis and communication with patients using
      fiber-optic transillumination and intraoral photography.
AB  - The diagnosis of incomplete cusp fractures has primarily relied on patient
      symptoms, which sometimes results in late treatment approaches. The
      transillumination of tooth structure by a fiber-optic light source can be
      considered an important adjunct tool in the diagnosis of incomplete cusp
      fractures before they reach their end stages. Furthermore, transilluminated teeth
      can be documented by intraoral photography, using a two-handed technique by
      holding a transillumination device and an intraoral camera simultaneously, with
      the resulting images shared with the patient. This simple, painless, and
      noninvasive technique can be incorporated easily into daily practice to evaluate
      high-risk sites, regardless of patient symptoms. This article reviews incomplete
      cusp fractures, explains how to detect them using transillumination and intraoral
      photography, and addresses how to discuss the results with patients.

PMID- 21903522
TI  - Diametral tensile strength of composite core material with cured and uncured
      fiber posts.
AB  - The aim of this study was to determine the influence of different types of posts
      and post head designs on the fracture resistance of a composite resin core
      material using the diametral tensile strength (DTS ). Seventy-five disc specimens
      were prepared using a composite core and prefabricated glass fiber posts and were
      divided into four test groups and one control group (n=15). The use of fiber
      posts reduced the DTS of the composite core material; the DTS value of the
      control material was significantly higher (p=0.05) than all of the test groups.

PMID- 21903524
TI  - Utility and effectiveness of computer-aided diagnosis of dental caries.
AB  - Digital radiography has created a growing opportunity for computer-aided
      diagnostic (CAD) tools. The Logicon Caries Detector (LCD), with upgraded CAD
      software based on user feedback, was re-evaluated for its effectiveness via a
      retrospective clinical study. Using the upgraded LCD software, 12 dentists
      (evaluators) blindly assessed 17 radiographs taken by another (attending)
      dentist, who restored 28 proximal surfaces. The attending dentist confirmed the
      presence of early dentinal caries, as well as identifying 48 surfaces as caries
      free or with enamel caries only subject to noninvasive treatment. The
      radiographs, imported into the software using a digital imaging and
      communications in medicine (DICOM) reader, were visually assessed under typical
      operatory lighting conditions, then with the aid of the software's density
      analysis tool. The effectiveness of the evaluators was gauged by calculating two
      measures of performance, sensitivity and specificity, for the detection and
      classification of dentinal caries. Sensitivity among all evaluator dentists was
      30% with the initial image; 34% with the brightness and contrast adjusted image;
      39% when the image was sharpened; and 69% when the density analysis tool was
      utilized. Specificity was found to be 97% with the initial image; 95% with the
      brightness and contrast adjusted image; 93% with the sharpened image; and 94%
      when the density analysis tool was used. Compared to the unaided eye, the LCD can
      significantly improve dentists' ability to detect and classify caries. Dentists
      may be able to find twice as much early dentinal caries requiring restoration (or
      at least aggressive noninvasive treatment) than previously, while not
      unnecessarily restoring additional healthy teeth. The LCD enables dentists to
      obtain more information from dental digital radiography than is possible with the
      unaided eye, leading to improved patient care.

PMID- 21903525
TI  - Management of multiple trauma avulsion of anterior primary teeth: a three-year
      follow-up.
AB  - Dental trauma can cause physical, esthetic, and psychological problems. This
      paper presents the case of a 2-year-old boy who suffered multiple avulsions of
      the maxillary anterior teeth. Treatment consisted of fixed orthodontic appliances
      with artificial anterior teeth. The clinical follow-up lasted for three years.
      The procedure for the re-establishment of esthetic and dental function was based
      on a simple, low-cost therapeutic solution. The child and parents were satisfied
      with the treatment results.

PMID- 21903526
TI  - Enalapril-induced angioedema: a dental concern.
AB  - Drug-induced angioedema is a rare but potentially life-threatening side effect of
      increased levels of bradykinin. It may be overlooked and diagnosed as a dental
      related problem due to its appearance as facial swelling. A clear understanding
      of the pathophysiology of angioedema can better serve both physicians and
      dentists in providing the most appropriate care for patients.

PMID- 21903527
TI  - Interdental papilla overgrowth. Peripheral odontogenic fibroma.

PMID- 21903528
TI  - Rubbery palatal mass. Inflammatory myofibroblastic tumor.

PMID- 21903529
TI  - Treatment of inflammatory external root resorption resulting from dental avulsion
      and pulp necrosis: clinical case report.
AB  - The aim of this case report was to present a treatment for severe inflammatory
      external root resorption. The condition developed due to the patient's neglect to
      seek adequate treatment following replantation of an avulsed maxillary left
      central incisor. Following diagnosis, treatment consisted of conventional
      endodontic therapy with calcium hydroxide dressings and definitive filling of the
      root canal after the resorption was controlled radiographically. A 24-month
      follow-up showed that the resorption process had stabilized and the patient was
      free of symptoms. Successful tooth replantation requires following the indicated
      therapy effectively. Nevertheless, when an inflammatory external root resorption
      occurs, adequate endodontic treatment to remove the necrotic content and bacteria
      is required, as is the use of calcium hydroxide dressings.

PMID- 21903530
TI  - Immediate provisional restoration of an implant placed in a fresh primary
      maxillary canine extraction socket: a case report.
AB  - This study describes a clinical case in which a primary maxillary canine with
      both mobility and root resorption was replaced with an immediately restored
      dental implant placed into the fresh extraction socket. The implant achieved high
      primary stability, as determined by resonance frequency analysis, and it was
      immediately restored with a provisional acrylic resin crown with no centric
      occlusion. An all-ceramic permanent crown replaced the provisonal crown four
      months after implant surgery. The implant was stable and no periapical
      radiolucencies, bleeding on probing, or pathologic probing depth were recorded
      after one year. The peri-implant soft tissue level appeared stable, and the
      interdental papillae were preserved, contributing to an optimum final esthetic
      result. This case supports the use of single implants for the replacement of
      extracted primary teeth, especially in areas where esthetics is a high priority.
      The immediate provisional crown maintained soft tissue contours and papillary
      height.

PMID- 21903531
TI  - Efficacy of antiplaque mouthwashes: a five-day clinical trial.
AB  - The aim of this study was to evaluate and compare the efficacy of antiplaque
      mouthwashes. Plaque levels were determined by applying a plaque-disclosing
      solution using the Turesky et al modification of the Quigley Hein plaque index.
      The control group (n = 6) brushed twice per day with fluoride toothpaste for one
      minute and rinsed with water, while the study groups (n = 6) brushed once per day
      with fluoride toothpaste for one minute, followed by rinsing with 5.0 mL of
      mouthwash diluted with 10.0 mL of water for 30 seconds. The control group brushed
      and rinsed with water twice per day. The results indicated that cetylpyridinium
      chloride in combination with sodium fluoride offered maximum plaque inhibition,
      followed by chlorhexidine gluconate and sodium monofluorophosphate, while plaque
      levels increased in the control group and with the combination of chlorhexidine
      gluconate and sodium fluoride. The only antiplaque agents to demonstrate a
      statistically significant difference from the control were cetylpyridinium
      chloride in combination with sodium fluoride, and chlorhexidine gluconate.
      Increasing the fluoride concentration had no impact on antiplaque activity.

PMID- 21903532
TI  - The effect of repeated firings on the color of feldspathic ceramics.
AB  - The aim of this study was to determine the extent to which repeated firings would
      change the color of feldspathic ceramics. Specimens were fabricated from five
      commercially available feldspathic ceramics using a circular stainless steel
      matrix 11 mm in diameter and 1.0 mm thick (n = 10, shade = A3). Repeated firings
      were performed and color analysis was completed with a colorimeter using the
      CIELA B color coordinates. Two-way ANOVA was used to analyze the data, followed
      by Tukey's post-hoc test (a = 0.05). Three factors were used as determinants: a,
      a measure of the chroma along the red-green axis; b, a measure of the chroma
      along the yellow-blue axis; and L, a measure of the lightness-darkness of the
      specimen on a scale from 0 (black) to 100 (white). The results indicated that a
      and b values increased and L values decreased after repeated firings, resulting
      in reddish, yellowish, and darker specimens, respectively (P = 0.001). As the
      number of firings increased, significant color alterations occurred in the color
      parameters of the specimens. These alterations resulted in color changes (delta
      E) that could be considered unacceptable in clinical practice.

PMID- 21903533
TI  - Sclerotherapy followed by surgery for the treatment of oral hemangioma: a report
      of two cases.
AB  - Hemangiomas, vascular malformations, and varices are common benign vascular
      lesions in the head and neck region. They can occur in the mouth and primarily
      affect the lips, tongue, buccal mucosa, and palate. The main types of treatments
      are surgery and intralesional injection of sclerosant agents. However, other
      therapies have been considered, such as systemic corticosteroids, laser therapy,
      interferon a, and cryotherapy. Currently, sclerotherapy is employed largely
      because of its efficiency and ability to conserve the surrounded tissues. Surgery
      can be used exclusively or associated with sclerotherapy in lesions that do not
      show complete resolution. This article describes the cases of two patients with
      oral hemangiomas that were submitted to sclerotherapy with ethanolamine oleate.
      Although an important decrease was detected after seven applications in both
      cases, surgical resection of the residual lesion was performed to achieve optimal
      results.

PMID- 21903534
TI  - Tobacco cessation efforts in dentistry: a rural state study.
AB  - The U.S. Department of Health and Human Services published Treating tobacco use
      and dependence: 2008 update to provide guidelines for treating tobacco use and
      dependence. These guidelines were developed based on a literature review with the
      goal of assisting clinicians in treating patients who use tobacco products. In
      2010, the authors conducted a survey of dentists and dental hygienists in a rural
      state with a high rate of tobacco use to determine dental providers' tobacco
      cessation efforts. The study found that the majority of clinicians surveyed ask
      about their patients' tobacco use at their initial examination and educate
      patients about the consequences of tobacco use. Still, improvements are possible
      with regard to identifying and documenting tobacco use. In addition, this
      research suggests that providers can become more confident in their cessation
      approach with patients and that additional referrals can be made for alternative
      cessation services.

PMID- 21903535
TI  - Alveolar ridge augmentation--a case series.
AB  - This study presents case reports of patients with osseous defects who were
      treated with autogenous bone grafts from the symphysis region, alloplast grafts
      with barrier membrane, and the use of free gingival onlay grafts for alveolar
      ridge augmentation. The patients were followed for a period of six months.

PMID- 21903536
TI  - Shear bond strength of two adhesive systems bonded to Er:YAG laser-prepared
      dentin.
AB  - Dentinal surfaces prepared with an Er:YAG laser have distinctly different
      characteristics compared to those prepared with conventional instruments. The
      objective of this study was to evaluate the shear bond strength of a total-etch
      adhesive system and a self-etch adhesive system to dentin, prepared
      conventionally or with an Er:YAG laser. Specimens that were prepared with a
      diamond bur and treated with the total-etch adhesive showed the highest mean bond
      strength, followed by specimens prepared with the laser and treated with the
      total-etch adhesive, specimens prepared with a diamond bur and treated with the
      self-etch adhesive, and specimens prepared with the laser and treated with the
      self-etch adhesive, but there were no differences among the groups (P > 0.05).
      These data indicate that the tested adhesive systems promote similar shear bond
      strengths, whether the dentin is prepared with a diamond bur or an Er:YAG laser,
      and that an Er:YAG laser is a suitable cavity preparation method that promotes an
      adequate surface for a posterior adhesive procedure.

PMID- 21903537
TI  - Listen to your heart.

PMID- 21903538
TI  - The sugar-loaded fentanyl lollipop (Actiq) and the risk for tooth decay.

PMID- 21903539
TI  - Educating and motivating patients for restorative dentistry.

PMID- 21903540
TI  - Full-mouth rehabilitation using both fixed and removable implant restorations.

PMID- 21903541
TI  - Benefits of additional courses of systemic azithromycin in periodontal therapy.
AB  - The use of systemic antimicrobials such as doxycycline, metronidazole, and
      azithromycin in conjunction with debridement has achieved results superior to
      those produced by debridement alone. The purpose of the present study was to
      determine if previous results could be improved upon by administering repeated
      doses of azithromycin during the hygiene phase. One hundred patients with
      moderate to advanced periodontitis were treated with scaling and root planing
      plus three courses of azithromycin during the hygiene phase. All patients then
      were re-evaluated and periodontal surgery and/or extractions involving 96 teeth
      were performed in 32 patients. All patients then entered a maintenance program
      that lasted up to 192 weeks, with four-month recalls. Clinical parameters were
      recorded at baseline, at re-evaluation (week 6 after baseline), and at 96 and 192
      weeks into maintenance. The results indicated that probing depths, bleeding upon
      probing, and suppuration were reduced significantly at re-evaluation. In
      addition, 14 teeth that displayed a Class III mobility at baseline improved to
      either Class I or Class II . There was no relapse during the maintenance phase.
      Multivariate analysis after 192 weeks indicated no change in the number of sites
      that bled upon probing, or had pockets that were 5.0-6.0 mm or >= 7 mm. Ninety
      five percent of the sites that initially bled upon probing did not do so four
      years post-treatment. The results indicate that three courses of azithromicin in
      conjunction with root instrumentation during the hygiene phase led to long
      lasting beneficial effects on all clinical parameters for at least 192 weeks.

PMID- 21903542
TI  - Improving the esthetic replacement of missing anterior teeth: interaction between
      periodontics and a rotational path removable partial denture.
AB  - The rotational path of insertion concept for removable partial dentures (RPDs)
      can be used in esthetically demanding situations. This clinical report describes
      the treatment of a patient with an anterior maxillary edentulous area using a
      rotational path RPD. To optimally improve gingival esthetics and to allow
      proximal retention on the surveyors, a crown-lengthening surgical procedure was
      performed prior to prosthetic treatment on all teeth involved in this
      rehabilitation. When correctly planned and fabricated, this prosthesis allows
      excellent functional and esthetic results, minimizes tooth preparation, and
      reduces the tendency toward plaque accumulation.

PMID- 21903543
TI  - Nonsurgical correction of Class III malocclusions: a new approach to treating
      late adolescents and adults.
AB  - This article describes a new nonsurgical orthodontic technique for correcting
      Class III malocclusions in the adult dentition when orthognathic surgery is not
      an option. Following a review of the dental literature pertaining to other
      nonsurgical orthodontic techniques, a nonextraction treatment protocol was
      established that utilized a mandibular distalizer combined with a maxillary
      transpalatal unit. Four cases were treated with this new treatment protocol and
      produced consistent results: anterior and posterior crossbites were corrected; a
      Class I molar relationship was established; both overbite and overjet were
      corrected; and there was no undesirable tipping of the mandibular molars.

PMID- 21903544
TI  - The use of a porcelain repair technique to improve the plane of occlusion of an
      existing restoration.
AB  - This article describes the use of an indirect porcelain repair technique to
      improve the occlusal relationship between a new fixed partial denture and an
      existing one. Porcelain repair techniques offer a conservative, minimally
      invasive, and cost-effective method of improving the opposing occlusion without
      replacing an existing restoration.

PMID- 21903545
TI  - Burning mouth syndrome: a challenge for dental practitioners and patients.
AB  - A retrospective study was conducted on patients with burning mouth syndrome (BMS)
      to assess demographics, onset characteristics, temporal behavior (frequency),
      duration, and progression of oral burning symptoms. Additionally, treatments
      provided by health practitioners prior to a definitive diagnosis of BMS were
      analyzed with an overview of current management strategies. The records of 49
      adult patients diagnosed with BMS were reviewed. Descriptive statistics and a
      Pearson correlation with a statistical significance at p < 0.05 were utilized to
      analyze the data. The majority of patients were mid-life white women who reported
      a sudden onset of constant oral burning symptoms that increased in intensity. On
      average, patients reported oral burning symptoms for 41 months (standard
      deviation = 73.5, range = 2-360 months, median = 20 months), and 38 of the
      patients received/trialed 71 various interventions (mean = 1.9) prior to
      receiving a definitive diagnosis for their oral burning symptoms. This study
      sample shared many characteristics with those reported previously in the
      literature. The authors found that patients frequently reported delays in
      receiving a definitive diagnosis with an array of various trialed interventions.
      For this reason, the authors provide this overview of current management
      strategies in order to assist dental practitioners in providing appropriate
      interventions for patients with BMS.

PMID- 21903546
TI  - Degree of microleakage of a self-etch sealant.
AB  - The purpose of this study was to compare the microleakage of a new self-etch
      sealant (Enamel Loc), with and without acid etching, to a traditional sealant
      (UltraSeal XT Plus) with acid etching in occlusal fissures. The self-etch sealant
      had significantly more microleakage than the traditional sealant or the self-etch
      sealant with acid-etching of the enamel.

PMID- 21903547
TI  - One-year clinical evaluation of oral rehabilitation after the loss of multiple
      primary teeth.
AB  - This article describes a one-year follow-up of the prosthetic rehabilitation of a
      child who lost multiple primary teeth due to widespread dental caries. Clinical
      and radiographic examinations indicated the need for all primary teeth to be
      extracted. Following the extractions, complete maxillary and mandibular removable
      prostheses with individualized occlusion and age-appropriate artificial teeth
      were fitted for functional and esthetic rehabilitation. The treatment improved
      the patient's speech, masticatory function, and facial esthetics, contributing to
      the development of normal dietary habits and social integration.

PMID- 21903548
TI  - Compressible tumor of the buccal mucosa. Vascular malformation.

PMID- 21903549
TI  - Painful lesion in the floor of the mouth. Squamous cell carcinoma.

PMID- 21903550
TI  - Slide crown lengthening procedure using wide surface incisions and cyanoacrylate.
AB  - This article introduces the slide crown lengthening procedure (SCLP), which
      incorporates surgical design features to overcome present crown lengthening
      procedure (CLP) shortcomings. The result is a 75% decrease in required surgery on
      adjacent teeth and a corresponding 75% reduction in surgical time. Other
      advantages include a reduction in surgical morbidity, improvement in terminal
      esthetics, and fewer teeth subject to papillae removal and apically repositioned
      gingiva. The 20 to 30 degree incision forming the slide is the pivotal feature;
      it allows effortless flap positioning. This incision angle enables wide surface
      incisions to adhere flaps together by producing stronger fibrin clots, decreasing
      tissue retraction angles, and reforming disrupted fibrin clots as incision sides
      slide while maintaining contact. This enhanced fibrin clot eliminates the need
      for sutures. The slide produced by the 20 to 30 degree incision functions for
      crown lengthening on all sites (facial, lingual, or palatal). This versatile
      surgical design introduces a new healing dimension that adapts to and provides
      benefits for other dental surgeries, such as gingival grafts, endodontic surgery,
      implants, and extractions.

PMID- 21903551
TI  - Implant-retained dentures for full-arch rehabilitation: a case report comparing
      fixed and removable restorations.
AB  - Dental implants as abutments for full-arch restorations are a well-documented
      treatment modality. This report presents a case in which the patient was treated
      initially with fixed restorations supported by either implants or natural teeth
      and subsequently treated with a removable implant/telescopic crown-supported
      overdenture. Advantages and disadvantages of each approach are described and
      discussed. While the fixed restoration resulted in a functionally satisfactory
      treatment outcome, the patient was displeased with the esthetic appearance. The
      main concern was the unnaturally long tooth shape necessary to compensate for the
      insufficient alveolar ridge height. Replacement of the existing restoration with
      an implant-supported removable overdenture led to a functionally and esthetically
      acceptable result. When deciding whether to use a fixed or removable implant
      supported full-arch restoration, a multitude of factors must be considered. Due
      to the possible need for additional surgical steps to enhance the esthetic
      appearance surrounding fixed restorations, removable implant-supported partial
      dentures often are the better choice.

PMID- 21903552
TI  - Effect of carbon and glass fiber posts on the flexural strength and modulus of
      elasticity of a composite resin.
AB  - The aim of this study was to evaluate the effect of prefabricated fiber posts on
      the flexural strength and modulus of elasticity of a composite resin. Thirty bar
      shaped specimens measuring 25 x 2.0 x 2.0 mm were made, containing posts that
      were 1.3 mm in diameter and 20 mm long. Each group contained 10 specimens: Group
      1, resin without post; Group 2, resin with carbon fiber post; Group 3, resin with
      glass fiber post. The samples were immersed in water at 37 degrees C until the
      three-point loading test was performed at a speed of 1.0 mm/minute. The results
      were statistically analyzed by ANOVA and Tukey's test (P = 0.05). Both fiber
      posts were similar in strength and both were stronger than the control. Group 3
      obtained a higher mean modulus of elasticity than Groups 1 and 2, which were
      similar. The results of this study demonstrated that the presence of a fiber post
      significantly raised flexural strength values and the glass fiber post
      significantly increased the modulus of elasticity of the evaluated composite
      resin.

PMID- 21903553
TI  - Effect of maintenance therapy with or without the use of chlorhexidine in teeth
      restored with composite resin in patients with diabetes mellitus.
AB  - The objective of this study was to evaluate the effects of maintenance therapy
      with or without the use of 0.12% chlorhexidine in the periodontal tissues of
      patients with diabetes mellitus who had carious lesions restored with composed
      resin. Twenty patients were selected, all of whom had diabetes mellitus in
      addition to carious cervical lesions in previously treated teeth. After 90 days,
      improvement in plaque and gingival indices and probing depth were noticed among
      patients in the group that received 0.12% chlorhexidine.

PMID- 21903554
TI  - Can traumatic occlusion cause endodontic problems? A case report.
AB  - Radicular cysts are commonly found odontogenic cysts in the jaws. The lesion is
      diagnosed mainly in young patients during the second decade of life. In the
      majority of cases, it is asymptomatic. This paper reports a rare case in which
      traumatic occlusion was identified as the etiology of a radicular cyst.
      Endodontic treatment was performed and the traumatic occlusion also was
      corrected. A six-month follow-up appointment found good healing of the periapical
      region.

PMID- 21903555
TI  - Influence of cement thickness and mechanical cycling on the push-out bond
      strength between posts and root dentin.
AB  - The aim of this study was to assess the influence of mechanical cycling and
      cement thickness on the bond strength between fiber posts and root dentin. Forty
      bovine teeth were sectioned (16 mm) and randomly assigned to four groups (n =
      10). Specimens in Groups 1 and 2 were cemented using a thinner cement layer,
      while specimens in Groups 3 and 4 were cemented using a thicker cement layer.
      Groups 2 and 4 were submitted to mechanical cycling. Four slices per specimen
      were produced and submitted to push-out testing. Bond strength values were not
      affected by mechanical cycling (P = 0.2893), although the thickness of the cement
      layer did affect bond strengths (P = 0.0059, thinner > thicker). Tukey's test
      showed that Group 1 (19.27 MPa) had a higher mean bond strength value than Group
      3 (12.4 MPa) and Group 4 (13.6 MPa), while Group 2 (15.0 MPa) was statistically
      similar to all groups. These results indicate that a thicker cement layer
      negatively affected the push-out bond strength between a fiber post and root
      dentin, regardless of whether the specimens were subjected to mechanical cycling.

PMID- 21903556
TI  - Ectopic eruption of permanent incisors after predecessor pulpectomy: five cases.
AB  - Pulpectomy in primary teeth is a common technique that preserves teeth in the
      oral environment and maintains or recovers periapical tissues to a healthy
      condition. This article describes the ectopic eruption of permanent incisors
      whose primary predecessors underwent pulpectomy using ZOE filler paste. In a
      group of 135 teeth that received pulpectomy therapy due to caries, 10 primary
      maxillary incisors had overretention and were followed for at least 3.5 years
      (mean time of 4.2 years), both clinically and radiographically, until the
      permanent teeth erupted. The proposed treatment included extraction of the
      overretained primary incisors based on permanent successor eruption chronology
      and contralateral eruption. Seven permanent teeth erupted ectopically.
      Autocorrection of the permanent tooth positions was observed in five cases. It
      can be concluded that periodic clinical and radiographic assessments are
      essential to verify radicular and filling paste resorptions and to avoid
      overretention and any subsequent malocclusion.

PMID- 21903557
TI  - Effect of radiotherapy on the hardness and surface roughness of two composite
      resins.
AB  - The knowledge about the potential adverse effects of radiotherapy compared to
      dental composites is a useful information for the clinician's decision regarding
      adoption of repairs or replacement of dental restorations during oral cancer
      treatment. This study evaluated the effects of irradiation on microhardness and
      surface roughness of a microfilled and a packable composite resin. The
      microfilled composite resin demonstrated significantly lower microhardness and a
      smoother surface compared to the packable composite resin (p < 0.05). Although
      irradiation significantly reduced the microhardness for both composite resins (P
      < 0.05), increasing the x-ray doses did not cause an additional significant
      decrease in surface hardness (P > 0.05). Meanwhile, irradiation did not produce a
      significantly rougher surface (P > 0.05), but specimens submitted to abrasion
      exhibited a significant increase in surface roughness for both composite resins
      (P < 0.05). It was concluded that while irradiation can adversely affect the
      hardness of tested composite resins, it does not interfere with surface
      roughness.

PMID- 21903558
TI  - Furcation lesion in a mandibular canine.
AB  - Morphological changes can complicate dental treatment. This report presents a
      rare case of a furcation lesion in a mandibular canine with two roots. A 39-year
      old man in general good health sought dental care for severe pain in his
      maxillary anterior teeth. The clinical examination showed localized swelling in
      the vestibular mucosa close to the mandibular left canine. Radiographic
      examination revealed two distinct roots and vertical bone resorption in the
      canine's mesial surface. Periodontal evaluation led to a diagnosis of periodontal
      abscess associated with furcation lesion. Despite the occurrence in an atypical
      location, the site of periodontal furcation received conventional therapy for
      initial decontamination, including tissue debridement and a combination of
      polyvinylpyrrolidone irrigation and antibiotics. To improve access, the
      decontamination was completed with surgical techniques and scaling and root
      planing. Early diagnosis of this rare morphological change helped to determine
      appropriate, timely treatment planning and optimal patient recovery.

PMID- 21903559
TI  - Regional odontodysplasia: management of an acute case with a scanning electron
      microscope.
AB  - Regional odontodysplasia (RO) is an uncommon, nonhereditary, odontogenic
      developmental disturbance characterized by hypoplasia and hypocalcification of
      the dental tissues that produce so-called "ghost teeth." This report describes a
      case of a 2.5-year-old girl who came to the clinic with RO affecting her right
      maxillary arch. The distinguishing characteristics of this case were the
      involvement of both the primary and permanent dentitions and the early occurrence
      of odontogenic abscesses that required the patient's hospitalization.
      Ultrastructural analysis revealed dental tissue failures that compromised the
      integrity of the involved teeth, justifying the high susceptibility to caries
      that was clinically observed. Follow-up was characterized by periodic prosthetic
      adjustments to maintain the patient's ability to masticate and for social
      interaction, beyond allowing normal development of her maxillofacial complex.
      Patients with RO require individualized treatment planning and close follow-up
      with a multidisciplinary approach.

PMID- 21903560
TI  - A rare case of dens evaginatus and dens invaginatus in the same tooth, with a
      review of treatment options.
AB  - Dens evaginatus (DE) and dens invaginatus (DI) are rare developmental anomalies
      of tooth formation. These variations in odontogenesis have been individually
      observed and reported in the literature. This report describes the radiographic
      appearance and management of a 16-year-old boy who came to the clinic with a rare
      occurrence of both DE and DI in the same tooth and examines the criteria used in
      identifying and classifying such anomalies. This report also discusses the
      importance of early identification and efficient management of dental anomalies,
      which can prevent irreversible pulpal pathology that requires endodontic therapy
      or tooth loss.

PMID- 21903561
TI  - No coasting allowed.

PMID- 21903562
TI  - FDA new drug approvals in 2010.

PMID- 21903563
TI  - Esthetic restoration of anterior teeth with adjacent osseointegrated implants.

PMID- 21903564
TI  - Curing lights--the LED invasion is complete.

PMID- 21903565
TI  - Current status of potential bisphenol toxicity in dentistry.
AB  - Bisphenols are chemical components found in dental composites and sealants.
      Similar compounds also can be found in baby bottles, food can liners, and even
      drinking water. Bisphenols have gained attention recently because they, like
      other natural and synthetic compounds, including hormone-based drugs and soybean
      products, have the capacity to mimic the actions of the hormone estrogen in
      living cells and animals. Such estrogenic activity has been linked to a variety
      of health problems, including breast and prostate cancer, metabolic disorders,
      and reproductive dysfunction. In early 2010, the FDA issued a report stating that
      there are some concerns about the safety of bisphenols in food products and
      called for more research on bisphenol toxicity. At present, no regulatory or
      professional organization has expressed concern about health effects of
      bisphenols in dental materials.

PMID- 21903566
TI  - Diagnosis and management of Bell's palsy.
AB  - Bell's palsy (BP) is an idiopathic peripheral facial nerve paralysis of sudden
      onset. Its most alarming symptom is unilateral facial weakness, which can result
      in the inability to close the eyelids, smile, or whistle. The pathogenesis of BP
      is controversial and is believed to be caused by inflammation of the facial nerve
      at the geniculate ganglion. Many viruses, especially herpes simplex and herpes
      zoster, have been suggested as initiators of this inflammatory process; however,
      this has not been proven. This report describes the case of a 14-year-old girl
      with right hemifacial palsy who sought treatment one month after the onset of
      palsy. The patient experienced a satisfactory recovery within 30 days of
      treatment and has maintained a stable physical outcome after 15 months of follow
      up. Early treatment based on careful investigation of BP, with particular
      attention given to the differential diagnosis of BP, can improve the patient's
      function and esthetics.

PMID- 21903567
TI  - Influence of conditioning time on bond strength: evaluation of self-etching
      adhesive systems.
AB  - The aim of this study was to evaluate the tensile bond strength of self-etching
      adhesive systems with different dentin conditioning times. Sixty caries-free,
      extracted third molars were selected, with the occlusal surface removed by a
      diamond saw disc. The specimens were embedded in epoxy resin and divided randomly
      into six groups (n = 10), according to the conditioning time and adhesive system
      used. After restoration, the specimens were stored in distilled water at room
      temperature for 24 hours; they then were submitted to the tensile bond strength
      test. The results were measured in MPa, then submitted to ANOVA and Tukey's test
      (P = 0.05). The adhesive system used and the length of dentin conditioning time
      were statistically significant (P < 0.05). The application time of the
      conditioner before photocuring did not have a significant effect on tensile bond
      strength. These results indicate that the resting time of adhesive above the
      dentin does not directly affect the bond strength of the adhesive system.

PMID- 21903568
TI  - Narrow band (light) imaging of oral mucosa in routine dental patients. Part I:
      Assessment of value in detection of mucosal changes.
AB  - The purpose of this investigation was to determine the value of adding narrow
      band (light) imaging (NBI) to the standard oral soft tissue examination process
      used to detect mucosal change. A total of 620 dental patients who came to the
      clinic for regular dental evaluation or for treatment of acute dental problems
      were given a standard oral soft tissue examination by dental students under
      faculty supervision. The results of the white light examination were recorded
      after the tissues were examined with NBI, at which point areas with a loss of
      fluorescence (LOF) were recorded. The nature of the tissue change was classified
      clinically as normal variation, inflammatory, traumatic, dysplastic, or other,
      and patients were categorized depending on their clinical findings: normal, need
      follow-up visit, or immediate biopsy. Risk factors related to oral dysplasia also
      were recorded. The addition of NBI added between one and two minutes to the
      examination process. Of the 620 examinations, an area with an LOF suggestive of
      pathology was detected in 69 subjects (11.1%). After a second immediate
      evaluation, 28 of the 69 subjects were scheduled for follow-up or biopsy. None of
      the lesions discovered in these 28 subjects had been detected using standard
      (white light) examination. Adding NBI to the routine clinical examination
      resulted in detection of changes not seen with white light examination in 11.1%
      of patients; of these, a small but important number were found to have otherwise
      undetected persistent changes representing inflammatory lesions or potentially
      dangerous oral dysplasia. Adding NBI as an adjunctive diagnostic procedure
      improved the quality and outcome of the examination process.

PMID- 21903569
TI  - Localized aggressive multiparous periodontitis: a newly documented entity.
AB  - This article describes a form of localized aggressive periodontitis (LAP) in
      young multiparous women and denotes this form of periodontitis as localized
      aggressive multiparous periodontitis (LAMP). The authors retrospectively reviewed
      six cases of LAP in healthy multiparous women who were followed clinically for
      more than five years, examining clinical histories, clinical findings, and
      radiographic features. Age, race, gender, parity, location of attachment loss,
      rate of attachment loss, and symptoms were recorded. LAMP is characterized by
      asymmetrical attachment loss along the distal proximal area of the maxillary
      and/or mandibular first permanent molars in multiparous females with a median age
      of 27. The mean annual rate of attachment loss in the maxillary first molars was
      calculated at 0.5 mm. LAMP progresses to involve the mandibular incisors but,
      unlike LAP, appears to spare the maxillary incisors. The authors suggest that
      LAMP is a recognizable periodontal disease that can be diagnosed in young,
      multiparous females via clinical history, periodontal examination, and
      radiographs. This study presents potential pathogenic pathways and suggests a
      possible answer to the paradox of why aging women become more edentulous than men
      despite better overall dental care.

PMID- 21903570
TI  - Oral erythema multiforme major: a triple case report.
AB  - This article presents three cases of erythema multiforme (EM) major with
      predominant oral mucosal lesions. Two males, aged 28 and 10, and a 19-year-old
      woman came to the clinic with oral vesiculoerosive lesions consistent with a
      diagnosis of EM major. All three patients reported histories consistent with an
      initial oral herpetic infection. Management with topical and systemic steroids
      resolved the lesions successfully in all three cases. The relatively recent
      literature has documented differences between EM and Stevens-Johnson syndrome. It
      is important for dentists to understand the etiology of EM and the associated
      diagnostic and management issues.

PMID- 21903571
TI  - Comparing primary and secondary wound healing discomfort after mandibular third
      molar surgery: a randomized, double-blind clinical trial.
AB  - Extraction of impacted mandibular third molars is one of the most common
      procedures in the oral cavity and often is followed by pain, swelling, and
      postextraction alveolitis and trismus. It has been suggested that postoperative
      discomfort is in relation to the type of surgical wound healing. The aim of this
      study was to compare pain, swelling, and maximum mouth opening in two groups of
      patients with primary and secondary wound healing after impacted mandibular third
      molar surgery. Thirty-two patients were enrolled in this study and randomly
      divided into two equal groups, quantitatively and by gender. After the surgical
      procedures, 16 patients received primary wound closure, while the other 16
      participants received secondary wound closure. A visual analog scale was used to
      collect pain data three days after the surgeries. A checklist was used to record
      data regarding swelling size and maximum mouth opening before, immediately
      following, three days after, and one week after surgery. Frequency tests and a t
      test were used for statistical analysis and a P value of <0.05 was considered to
      be statistically significant. Patients in the secondary wound healing group
      showed statistically significant lower discomfort regarding pain, swelling size,
      and maximal mouth opening compared to the primary wound healing group. The
      authors suggest the use of secondary wound healing closure to reduce
      postoperative complications such as pain, maximal mouth opening, and swelling
      size after impacted mandibular third molar extractions.

PMID- 21903572
TI  - Altered mandibular anatomy. Systemic sclerosis.

PMID- 21903573
TI  - Mandibular radiolucency. Venous malformation.

PMID- 21903574
TI  - FGF-23 associates with death, cardiovascular events, and initiation of chronic
      dialysis.
AB  - Concentrations of the phosphate-regulating hormone fibroblast growth factor-23
      (FGF-23) are elevated in patients with chronic kidney disease (CKD), but whether
      higher plasma FGF-23 concentrations associate with all-cause mortality,
      cardiovascular events, or initiation of chronic dialysis is not completely
      understood. Here, we measured FGF-23 concentration in stored plasma samples from
      1099 patients with advanced CKD who participated in The Homocysteine in Kidney
      and End Stage Renal Disease study. Mean serum phosphorus concentration was 4.3
      mg/dl, median FGF-23 concentration was 392 RU/ml, and mean GFR was 18 ml/min/1.73
      m(2). During a median follow-up of 2.9 yr, 453 (41%) patients died from any
      cause, 215 (20%) had a cardiovascular event, and 615 (56%) initiated chronic
      dialysis. Compared with the lowest quartile of FGF-23, each subsequent quartile
      associated with a progressively higher risk for death, adjusted for confounders
      (HR [95% CI] of 1.24 [0.91 to 1.69], 1.76 [1.28 to 2.44], and 2.17 [1.56 to 3.08]
      for the second through fourth quartiles, respectively). In addition, compared
      with the lowest quartile, the two highest quartiles of FGF-23 also associated
      with a significantly elevated risk for cardiovascular events and initiation of
      chronic dialysis. In conclusion, in advanced CKD, FGF-23 strongly and
      independently associates with all-cause mortality, cardiovascular events, and
      initiation of chronic dialysis.

PMID- 21903575
TI  - Mitotic centromere-associated kinesin (MCAK) mediates paclitaxel resistance.
AB  - Paclitaxel has powerful anticancer activity, but some tumors are inherently
      resistant to the drug, whereas others are initially sensitive but acquire
      resistance during treatment. To deal with this problem, it will be necessary to
      understand the mechanisms of drug action and resistance. Recent studies indicate
      that paclitaxel blocks cell division by inhibiting the detachment of microtubules
      from centrosomes. Here, we demonstrate that mitotic centromere-associated kinesin
      (MCAK), a kinesin-related protein that destabilizes microtubules, plays an
      important role in microtubule detachment. Depletion of MCAK altered mitotic
      spindle morphology, increased the frequency of lagging chromosomes, and inhibited
      the proliferation of WT CHO cells, confirming that it is an essential protein for
      cell division. In contrast, MCAK depletion rescued the proliferation of mutant
      paclitaxel-dependent cell lines that are unable to divide because of defective
      spindle function resulting from altered alpha-tubulin or class III beta-tubulin
      overexpression. In concert with the correction of mitotic defects, loss of MCAK
      reversed an aberrantly high frequency of microtubule detachment in the mutant
      cells and increased their sensitivity to paclitaxel. The results indicate that
      MCAK affects cell sensitivity to mitotic inhibitors by modulating the frequency
      of microtubule detachment, and they demonstrate that changes in a microtubule
      interacting protein can reverse the effects of mutant tubulin expression.

PMID- 21903576
TI  - Control of protein kinase C activity, phorbol ester-induced cytoskeletal
      remodeling, and cell survival signals by the scaffolding protein
      SSeCKS/GRAVIN/AKAP12.
AB  - The product of the SSeCKS/GRAVIN/AKAP12 gene ("SSeCKS") is a major protein kinase
      (PK) C substrate that exhibits tumor- and metastasis-suppressing activity likely
      through its ability to scaffold multiple signaling mediators such as PKC, PKA,
      cyclins, calmodulin, and Src. Although SSeCKS and PKCalpha bind
      phosphatidylserine, we demonstrate that phosphatidylserine-independent binding of
      PKC by SSeCKS is facilitated by two homologous SSeCKS motifs,
      EG(I/V)(T/S)XWXSFK(K/R)(M/L)VTP(K/R)K(K/R)X(K/R)XXXEXXXE(E/D) (amino acids 592
      620 and 741-769). SSeCKS binding to PKCalpha decreased kinase activity and was
      dependent on the two PKC-binding motifs. SSeCKS scaffolding of PKC was increased
      in confluent cell cultures, correlating with significantly increased SSeCKS
      protein levels and decreased PKCalpha activity, suggesting a role for SSeCKS in
      suppressing PKC activation during contact inhibition. SSeCKS-null mouse embryo
      fibroblasts displayed increased relative basal and phorbol ester (phorbol 12
      myristate 13-acetate)-induced PKC activity but were defective in phorbol 12
      myristate 13-acetate-induced actin cytoskeletal reorganization and cell shape
      change; these responses could be rescued by the forced expression of full-length
      SSeCKS but not by an SSeCKS variant deleted of its PKC-binding domains. Finally,
      the PKC binding sites in SSeCKS were required to restore cell rounding and/or
      decreased apoptosis in phorbol ester-treated LNCaP, LNCaP-C4-2, and MAT-LyLu
      prostate cancer cells. Thus, PKC-mediated remodeling of the actin cytoskeleton is
      likely regulated by the ability of SSeCKS to control PKC signaling and activity
      through a direct scaffolding function.

PMID- 21903577
TI  - Growth and shortening of microtubules: a two-state model approach.
AB  - In this study, a two-state mechanochemical model is presented to describe the
      dynamic instability of microtubules (MTs) in cells. The MT switches between two
      states, the assembly and disassembly states. In assembly state, the growth of MTs
      includes two processes: free GTP-tubulin binding to the tip of protofilament (PF)
      and conformation change of PF, during which the first tubulin unit that curls
      outwards is rearranged onto the MT surface, using the energy released from the
      hydrolysis of GTP in the penultimate tubulin unit. In the disassembly state, the
      shortening of MTs also includes two processes, the release of GDP-tubulin from
      the tip of PF and the curling of one new tubulin unit out of the MT surface.
      Switches between these two states, which are usually called rescue and
      catastrophe, happen stochastically with external force-dependent rates. Using
      this two-state model with parameters obtained by fitting the recent experimental
      data, detailed properties of MT growth are obtained. I find that MT is mainly in
      the assembly state, its mean growth velocity increases with both the external
      force and the GTP-tubulin concentration, and an MT will shorten on average
      without an external force. To know more about the external force and GTP-tubulin
      concentration-dependent properties of MT growth, and for future experimental
      verification of this two-state model, 11 critical forces are defined and
      discussed numerically.

PMID- 21903578
TI  - Desmin regulates airway smooth muscle hypertrophy through early growth-responsive
      protein-1 and microRNA-26a.
AB  - Bronchial biopsies of asthmatic patients show a negative correlation desmin
      expression in airway smooth muscle cell (ASMC) and airway hyperresponsiveness. We
      previously showed that desmin is an intracellular load-bearing protein, which
      influences airway compliance, lung recoil, and airway contractile responsiveness
      (Shardonofsky, F. R., Capetanaki, Y., and Boriek, A. M. (2006) Am. J. Physiol.
      Lung Cell. Mol. Physiol. 290, L890-L896). These results suggest that desmin may
      play an important role in ASMC homeostasis. Here, we report that ASMCs of desmin
      null mice (ASMCs(Des-/-)) show hypertrophy and up-regulation microRNA-26a (miR
      26a). Knockdown of miR-26a in ASMCs(Des-/-) inhibits hypertrophy, whereas
      enforced expression of miR-26a in ASMCs(Des+/+) induces hypertrophy. We identify
      that Egr1 (early growth responsive protein-1) activates miR-26a promoter via
      enhanced phosphorylation of Erk1/2 in ASMCs(Des-/-). We show glycogen synthase
      kinase-3beta (GSK-3beta) as a target gene of miR-26a. Moreover, induction of
      ASMCs(Des-/-) hypertrophy by the Erk-1/2/Egr-1/miR-26a/GSK-3beta pathway is
      consistent in human recombinant ASMCs, which stably suppresses 90% endogenous
      desmin expression. Overall, our data demonstrate a novel role for desmin as an
      anti-hypertrophic protein necessary for ASMC homeostasis and identifies desmin as
      a novel regulator of microRNA.

PMID- 21903579
TI  - p53-independent epigenetic repression of the p21(WAF1) gene in T-cell acute
      lymphoblastic leukemia.
AB  - The p53 protein is a primary mediator of cellular apoptosis and growth arrest
      after exposure to DNA-damaging agents. Previous work has shown that the majority
      of childhood acute lymphoblastic leukemia (ALL) cases express a wild type p53
      gene, although the functionality of the p53 pathway has rarely been validated. In
      the present study, the integrity of the p53 pathway was investigated in a panel
      of ALL cell lines and xenografts established from direct patient explants in
      immune-deficient mice. A focused real-time quantitative reverse transcription PCR
      array of known p53-regulated genes identified p21(WAF1) (CDKN1A) as the highest
      ranked gene to be differentially expressed between B-cell precursor (BCP)-ALL and
      T-ALL xenografts following exposure to the DNA-damaging drug etoposide. Lack of
      p21(WAF1) induction was observed in six of seven T-ALL xenograft lines, as well
      as primary T-ALL cells following irradiation exposure, despite an otherwise
      functional p53 response. Repression of p21(WAF1) in T-ALL cells was associated
      with decreased acetylated H3K9 localized at its promoter compared with BCP-ALL
      cells, together with increased CpG methylation within the first exon and intron.
      Although the histone deacetylase inhibitor vorinostat failed to induce p21(WAF1)
      in T-ALL samples, the combination of vorinostat and the demethylating agent
      decitabine reactivated expression of the silenced p21(WAF1) gene in the Molt-4 T
      ALL cell line. Considering the known anti-apoptotic function of p21(WAF1), our
      findings have significant implications for the responses of T- versus BCP-ALL
      cells to chemotherapeutic drugs that induce p21(WAF1).

PMID- 21903580
TI  - 5-aza-2'-deoxycytidine activates iron uptake and heme biosynthesis by increasing
      c-Myc nuclear localization and binding to the E-boxes of transferrin receptor 1
      (TfR1) and ferrochelatase (Fech) genes.
AB  - The hypomethylating agent 5-aza-2'-deoxycytidine (5-aza-CdR) and its derivatives
      have been successfully used for the treatment of myelodysplastic syndromes, and
      they frequently improve the anemia that usually accompanies these disorders.
      However, the molecular mechanisms underlying this action remain poorly
      understood. In this study, we used two erythroid models, murine erythroid
      leukemia cells and erythroid burst-forming unit-derived erythroblasts, to show
      that 5-aza-CdR induced erythroid differentiation and increased the expression of
      transferrin receptor 1 (TfR1) and ferrochelatase (Fech), thereby increasing iron
      uptake and heme biosynthesis. We have identified new regulatory E-boxes that lie
      outside of CpG islands in the TfR1 and Fech promoters, and the methylation status
      of these sites can be altered by 5-aza-CdR treatment. This in turn altered the
      binding of the transcription factor c-Myc to these promoter elements.
      Furthermore, 5-aza-CdR promoted the nuclear translocation of c-Myc and its
      binding to Max to form functional complexes. The coordinated actions of 5-aza-CdR
      on the methylation status of the target genes and in stimulating the nuclear
      translocation of c-Myc provide new molecular insights into the regulation of E
      boxes and explain, at least in part, the increased erythroid response to 5-aza
      CdR treatment.

PMID- 21903581
TI  - Two-pore channels form homo- and heterodimers.
AB  - Two-pore channels (TPCs) have been recently identified as NAADP-regulated Ca(2+)
      release channels, which are localized on the endolysosomal system. TPCs have a 12
      transmembrane domain (TMD) structure and are evolutionary intermediates between
      the 24-TMD alpha-subunits of Na(+) or Ca(2+) channels and the transient receptor
      potential channel superfamily, which have six TMDs in a single subunit and form
      tetramers with 24 TMDs as active channels. Based on this relationship, it is
      predicted that TPCs dimerize to form functional channels, but the dimerization of
      human TPCs has so far not been studied. Using co-immunoprecipitation studies and
      a mass spectroscopic analysis of the immunocomplex, we show the presence of homo-
      and heteromeric complexes for human TPC1 and TPC2. Despite their largely distinct
      localization, we identified a discrete number of endosomes that coexpressed TPC1
      and TPC2. Homo- and heteromerization were confirmed by a FRET study, showing that
      both proteins interacted in a rotational (N- to C-terminal/head-to-tail)
      symmetry. This is the first report describing the presence of homomultimeric TPC1
      channels and the first study showing that TPCs are capable of forming heteromers.

PMID- 21903582
TI  - Elevated CO(2) levels cause mitochondrial dysfunction and impair cell
      proliferation.
AB  - Elevated CO(2) concentrations (hypercapnia) occur in patients with severe lung
      diseases. Here, we provide evidence that high CO(2) levels decrease O(2)
      consumption and ATP production and impair cell proliferation independently of
      acidosis and hypoxia in fibroblasts (N12) and alveolar epithelial cells (A549).
      Cells exposed to elevated CO(2) died in galactose medium as well as when glucose
      6-phosphate isomerase was knocked down, suggesting mitochondrial dysfunction.
      High CO(2) levels led to increased levels of microRNA-183 (miR-183), which in
      turn decreased expression of IDH2 (isocitrate dehydrogenase 2). The high CO(2)
      induced decrease in cell proliferation was rescued by alpha-ketoglutarate and
      overexpression of IDH2, whereas proliferation decreased in normocapnic cells
      transfected with siRNA for IDH2. Also, overexpression of miR-183 decreased IDH2
      (mRNA and protein) as well as cell proliferation under normocapnic conditions,
      whereas inhibition of miR-183 rescued the normal proliferation phenotype in cells
      exposed to elevated levels of CO(2). Accordingly, we provide evidence that high
      CO(2) induces miR-183, which down-regulates IDH2, thus impairing mitochondrial
      function and cell proliferation. These results are of relevance to patients with
      hypercapnia such as those with chronic obstructive pulmonary disease, asthma,
      cystic fibrosis, bronchopulmonary dysplasia, and muscular dystrophies.

PMID- 21903583
TI  - Crystal structures of multicopper oxidase CueO bound to copper(I) and silver(I):
      functional role of a methionine-rich sequence.
AB  - The multicopper oxidase CueO oxidizes toxic Cu(I) and is required for copper
      homeostasis in Escherichia coli. Like many proteins involved in copper
      homeostasis, CueO has a methionine-rich segment that is thought to be critical
      for copper handling. How such segments function is poorly understood. Here, we
      report the crystal structure of CueO at 1.1 A with the 45-residue methionine-rich
      segment fully resolved, revealing an N-terminal helical segment with methionine
      residues juxtaposed for Cu(I) ligation and a C-terminal highly mobile segment
      rich in methionine and histidine residues. We also report structures of CueO with
      a C500S mutation, which leads to loss of the T1 copper, and CueO with six
      methionines changed to serine. Soaking C500S CueO crystals with Cu(I), or wild
      type CueO crystals with Ag(I), leads to occupancy of three sites, the previously
      identified substrate-binding site and two new sites along the methionine-rich
      helix, involving methionines 358, 362, 368, and 376. Mutation of these residues
      leads to a ~4-fold reduction in k(cat) for Cu(I) oxidation. Ag(I), which often
      appears with copper in nature, strongly inhibits CueO oxidase activities in vitro
      and compromises copper tolerance in vivo, particularly in the absence of the
      complementary copper efflux cus system. Together, these studies demonstrate a
      role for the methionine-rich insert of CueO in the binding and oxidation of Cu(I)
      and highlight the interplay among cue and cus systems in copper and silver
      homeostasis.

PMID- 21903584
TI  - Neuronal death induced by nanomolar amyloid beta is mediated by primary
      phagocytosis of neurons by microglia.
AB  - Alzheimer disease is characterized by neuronal loss and brain plaques of
      extracellular amyloid beta (Abeta), but the means by which Abeta may induce
      neuronal loss is not entirely clear. Although high concentrations of Abeta (MUM)
      can induce direct toxicity to neurons, we find that low concentration (nM) induce
      neuronal loss through a microglia-mediated mechanism. In mixed neuronal-glial
      cultures from rat cerebellum, 250 nM Abeta1-42 (added as monomers, oligomers or
      fibers) induced about 30% loss of neurons between 2 and 3 days. This neuronal
      loss occurred without any increase in neuronal apoptosis or necrosis, and no
      neuronal loss occurred with Abeta42-1. Abeta greatly increased the phagocytic
      capacity of microglia and induced phosphatidylserine exposure (an "eat-me"
      signal) on neuronal processes. Blocking exposed phosphatidylserine by adding
      annexin V or an antibody to phosphatidylserine or inhibiting microglial
      phagocytosis by adding either cytochalasin D (to block actin polymerization) or
      cyclo(RGDfV) (to block vitronectin receptors) significantly prevented neuronal
      loss. Loss of neuronal synapses occurred in parallel with loss of cell bodies and
      was also prevented by blocking phagocytosis. Inhibition of phagocytosis prevented
      neuronal loss with no increase in neuronal death, even after 7 days, suggesting
      that microglial phagocytosis was the primary cause of neuronal death induced by
      nanomolar Abeta.

PMID- 21903585
TI  - RAD51-associated protein 1 (RAD51AP1) interacts with the meiotic recombinase DMC1
      through a conserved motif.
AB  - Homologous recombination (HR) reactions mediated by the RAD51 recombinase are
      essential for DNA and replication fork repair, genome stability, and tumor
      suppression. RAD51-associated protein 1 (RAD51AP1) is an important HR factor that
      associates with and stimulates the recombinase activity of RAD51. We have
      recently shown that RAD51AP1 also partners with the meiotic recombinase DMC1,
      displaying isoform-specific interactions with DMC1. Here, we have characterized
      the DMC1 interaction site in RAD51AP1 by a series of truncations and point
      mutations to uncover a highly conserved WVPP motif critical for DMC1 interaction
      but dispensable for RAD51 association. This RAD51AP1 motif is reminiscent of the
      FVPP motif in the tumor suppressor protein BRCA2 that mediates DMC1 interaction.
      These results further implicate RAD51AP1 in meiotic HR via RAD51 and DMC1.

PMID- 21903586
TI  - miR-125b, a target of CDX2, regulates cell differentiation through repression of
      the core binding factor in hematopoietic malignancies.
AB  - MicroRNA-125b (miR-125b), a small noncoding RNA molecule, has been found to be
      deregulated and functions as an oncogene in many cancers including hematopoietic
      malignancies. However, the mechanisms accounting for miR-125b dysregulation
      remain to be elucidated. The present study aims to identify the factors that
      might contribute to up-regulation of miR-125b in human hematopoietic malignancies
      and its downstream targets for lineage-specific differentiation. We at first
      reported that CDX2, a homeobox transcription factor, binds to promoter regions of
      the miR-125b gene and activates transcriptional regulation of miR-125b in
      malignant myeloid cells. We further revealed that increasing levels of CDX2 in
      malignant myeloid cells activate miR-125b expression, which in turn inhibits core
      binding factor beta (CBFbeta) translation, thereby counteracting myeloid cell
      differentiation, at least for granulocytic lineage, and promoting leukemogenesis.
      Interestingly, we found that this novel pathway including CDX2, miR-125b, and
      CBFbeta was mediated by undergoing all-trans-retinoic acid induction. Once
      differentiation ensues with all-trans-retinoic acid treatment, CDX2 activity
      decreases, leading to a reduction in miR-125b transcription and up-regulation of
      CBFbeta in myeloid cells and in patients. The study provides a new mechanism that
      contributes to hematopoietic malignancies, which could involve deregulation of
      miR-125b and its up- and downstream factors. As altered expression of miRNAs has
      been reported in a wide range of malignancies, delineating the underlying
      molecular mechanisms of aberrant miRNA expression and characterizing the upstream
      and downstream factors will help to understand important steps in the
      pathogenesis of these afflictions.

PMID- 21903587
TI  - Discrete M3-M4 intracellular loop subdomains control specific aspects of gamma
      aminobutyric acid type A receptor function.
AB  - The GABA type A receptor (GABA(A)R) is a member of the pentameric ligand gated
      ion channel (pLGIC) family that mediates ionotropic neurotransmission. Residues
      in the intracellular loop domain (ILD) have recently been shown to define part of
      the ion permeation pathway in several closely related members of the pentameric
      ligand gated ion channel family. In this study, we investigated the role the ILD
      of the GABA(A)R alpha1 subunit plays in channel function. Deletion of the alpha1
      ILD resulted in a significant increase in GABA EC(50) and maximal current
      amplitude, suggesting that the ILD must be intact for proper receptor function.
      To test this hypothesis, we conducted a mutagenic screen of all amino acids
      harboring ionizable side chains within this domain to investigate the
      contribution of individual charged residues to ion permeation. Using macroscopic
      and single channel voltage-clamp recording techniques, we found that mutations
      within a subdomain of the alpha1 ILD near M3 altered GABA apparent affinity;
      interestingly, alpha1(K312E) exhibited reduced partial agonist efficacy. We
      introduced point mutations near M4, including alpha1(K383E) and alpha1(K384E),
      that enhanced receptor desensitization. Mutation of 5 charged residues within a
      39-residue span contiguous with M4 reduced relative anion permeability of the
      channel and may represent a weak intracellular selectivity filter. Within this
      subdomain, the alpha1(K378E) mutation induced a significant reduction in single
      channel conductance, consistent with our hypothesis that the GABA(A)R alpha1 ILD
      contributes directly to the permeation pathway.

PMID- 21903588
TI  - Characterization of Cholix toxin-induced apoptosis in HeLa cells.
AB  - Cholix toxin (Cholix) is a novel ADP-ribosylating cytotoxin produced by Vibrio
      cholerae, which utilizes eukaryotic elongation factor 2 as a substrate and acts
      by a mechanism similar to that of diphtheria toxin and Pseudomonas exotoxin A.
      First it was found that Cholix-treated HeLa cells exhibited caspase-dependent
      apoptosis, whereas intestinal cells such as Caco-2, HCT116, and RKO did not. Here
      we investigated Cholix-induced cell death signaling pathways in HeLa cells.
      Cholix-induced cytochrome c release into cytosol was initiated by specific
      conformational changes of pro-apoptotic Bak associated with Bax. Silencing of
      bak/bax genes or bak gene alone using siRNA significantly suppressed cytochrome c
      release and caspase-7 activation, but not activation of caspases-3 and -9.
      Although pretreatment with a caspase-8 inhibitor (Z-IETD-FMK) reduced Cholix
      induced cytochrome c release and activation of caspases-3, -7, and -9,
      cytotoxicity was not decreased. Pretreatment with Z-YVAD-FMK, which inhibits
      caspase-1, -4, and -5, suppressed not only cytochrome c release, activation of
      caspase-3, -7, -8, or -9, and PARP cleavage, but also cytotoxicity, indicating
      that caspase-1, -4, and -5 activation is initiated at an early stage of Cholix
      induced apoptosis and promotes caspase-8 activation. These results show that the
      inflammatory caspases (caspase-1, -4, and -5) and caspase-8 are responsible for
      both mitochondrial signals and other caspase activation. In conclusion, we showed
      that Cholix-induced caspase activation plays an essential role in generation of
      apoptotic signals, which are mediated by both mitochondria-dependent and 
      independent pathways.

PMID- 21903589
TI  - Oncogenic ras-induced down-regulation of pro-apoptotic protease caspase-2 is
      required for malignant transformation of intestinal epithelial cells.
AB  - Resistance of carcinoma cells to anoikis, apoptosis that is normally induced by
      loss of cell-to-extracellular matrix adhesion, is thought to be essential for the
      ability of these cells to form primary tumors, invade adjacent tissues, and
      metastasize to distant organs. Current knowledge about the mechanisms by which
      cancer cells evade anoikis is far from complete. In an effort to understand these
      mechanisms, we found that ras, a major oncogene, down-regulates protease caspase
      2 (which initiates certain steps of the cellular apoptotic program) in malignant
      human and rat intestinal epithelial cells. This down-regulation could be reversed
      by inhibition of a protein kinase Mek, a mediator of Ras signaling. We also found
      that enforced down-regulation of caspase-2 in nonmalignant intestinal epithelial
      cells by RNA interference protected them from anoikis. Furthermore, the reversal
      of the effect of Ras on caspase-2 achieved by the expression of exogenous caspase
      2 in detached ras-transformed intestinal epithelial cells promoted well
      established apoptotic events, such as the release of the pro-apoptotic
      mitochondrial factors cytochrome c and HtrA2/Omi into the cytoplasm of these
      cells, significantly enhanced their anoikis susceptibility, and blocked their
      long term growth in the absence of adhesion to the extracellular matrix. Finally,
      the blockade of the effect of Ras on caspase-2 substantially suppressed growth of
      tumors formed by the ras-transformed cells in mice. We conclude that ras-induced
      down-regulation of caspase-2 represents a novel mechanism by which oncogenic Ras
      protects malignant intestinal epithelial cells from anoikis, promotes their
      anchorage-independent growth, and allows them to form tumors in vivo.

PMID- 21903590
TI  - MYC protein inhibits transcription of the microRNA cluster MC-let-7a-1~let-7d via
      noncanonical E-box.
AB  - The human microRNA cluster MC-let-7a-1~let-7d, with three members let-7a-1, let
      7f-1, and let-7d, is an important cluster of the let-7 family. These microRNAs
      play critical roles in regulating development and carcinogenesis. Therefore,
      precise control of MC-let-7a-1~let-7d level is critical for cellular functions.
      In this study, we first showed that the expression of these three members was
      significantly reduced in human hepatocellular carcinoma HepG2 cells as compared
      with the immortalized human liver L02 cells. We demonstrated that the MC-let-7a
      1~let-7d cluster was encoded by a single polycistronic transcript driven by a 10
      kb upstream promoter, with two MYC-binding sites. Importantly, MYC inhibited MC
      let-7a-1~let-7d promoter activity via binding to the noncanonical E-box 3
      downstream of the transcription start sites, whereas it enhanced promoter
      activity by binding to the canonical E-box 2 upstream of the transcription start
      sites. We found that although the binding affinity of MYC to E-box 2 was stronger
      than E-box 3, the binding quantum of MYC to E-box 3 was significantly higher in
      cancerous HepG2 cells as compared with the noncancerous L02 cells. In addition,
      forced expression of let-7 could reverse the MYC-mediated cell proliferation.
      These findings suggested that in L02 cells with a low level of MYC, MYC binds
      mainly to E-box 2 to enhance MC-let-7a-1~let-7d expression. However, in HepG2
      cells with an elevated MYC, the extra MYC could bind to E-box 3 to suppress the
      transcription of MC-let-7a-1~let-7d and thus enable HepG2 cells to maintain a
      high level of MYC and a low level of let-7 microRNAs simultaneously.

PMID- 21903591
TI  - Antagonists of anaphase-promoting complex (APC)-2-cell cycle and apoptosis
      regulatory protein (CARP)-1 interaction are novel regulators of cell growth and
      apoptosis.
AB  - CARP-1/CCAR1, a perinuclear phosphoprotein, is a regulator of cell growth and
      apoptosis signaling. Although CARP-1 is a regulator of chemotherapy-dependent
      apoptosis, it is also a part of the NF-kappaB proteome and a co-activator of
      steroid/thyroid nuclear receptors as well as beta-catenin signaling. Our yeast
      two-hybrid screen revealed CARP-1 binding with the anaphase-promoting
      complex/cyclosome E3 ubiquitin ligase component APC-2 protein. CARP-1 also binds
      with anaphase-promoting complex/cyclosome co-activators Cdc20 and Cdh1. Following
      mapping of the minimal epitopes involved in CARP-1 binding with APC-2, a
      fluorescence polarization assay was established that indicated a dissociation
      constant (K(d)) of 480 nm for CARP-1/APC-2 binding. Fluorescence polarization
      assay-based high throughput screening of a chemical library yielded several small
      molecule antagonists of CARP-1/APC-2 binding, termed CARP-1 functional mimetics.
      CFM-4 (1(2-chlorobenzyl)-5'-phenyl-3'H-spiro[indoline-3,2'-[1,3,4]thiadiazol]-2
      one), a lead compound, binds with and stimulates CARP-1 expression. CFM-4
      prevents CARP-1 binding with APC-2, causes G(2)M cell cycle arrest, and induces
      apoptosis with an IC(50) range of 10-15 MUm. Apoptosis signaling by CFM-4
      involves activation of caspase-8 and -9 and caspase-mediated ubiquitin-proteasome
      pathway-independent loss of cyclin B1 and Cdc20 proteins. Depletion of CARP-1,
      however, interferes with CFM-4-dependent cell growth inhibition, activation of
      caspases, and apoptosis. Because CFM-4 also suppresses growth of drug-resistant
      human breast cancer cells without affecting the growth of human breast epithelial
      MCF-10A cells, elevating CARP-1 by CFM-4 and consequent apoptosis could in
      principle be exploited to further elucidate, and perhaps effectively target,
      often deregulated cell cycle pathways in pathological conditions, including
      cancer.

PMID- 21903593
TI  - Top-down dimensional weight set determines the capture of visual attention:
      evidence from the PCN component.
AB  - Visual search for feature singletons is slowed when a task-irrelevant, but more
      salient distracter singleton is concurrently presented. While there is a
      consensus that this distracter interference effect can be influenced by internal
      system settings, it remains controversial at what stage of processing this
      influence starts to affect visual coding. Advocates of the "stimulus-driven" view
      maintain that the initial sweep of visual processing is entirely driven by
      physical stimulus attributes and that top-down settings can bias visual
      processing only after selection of the most salient item. By contrast, opponents
      argue that top-down expectancies can alter the initial selection priority, so
      that focal attention is "not automatically" shifted to the location exhibiting
      the highest feature contrast. To precisely trace the allocation of focal
      attention, we analyzed the Posterior-Contralateral-Negativity (PCN) in a task in
      which the likelihood (expectancy) with which a distracter occurred was
      systematically varied. Our results show that both high (vs. low) distracter
      expectancy and experiencing a distracter on the previous trial speed up the
      timing of the target-elicited PCN. Importantly, there was no distracter-elicited
      PCN, indicating that participants did not shift attention to the distracter
      before selecting the target. This pattern unambiguously demonstrates that
      preattentive vision is top-down modifiable.

PMID- 21903592
TI  - Hydrophilic residues are crucial for ribosomal protein L11 (RPL11) interaction
      with zinc finger domain of MDM2 and p53 protein activation.
AB  - Ribosomal protein L11 (RPL11) has been shown to activate p53 by binding to MDM2
      and negating its p53 suppression activity in response to ribosomal stress.
      Although a mutation at Cys-305 within the zinc finger domain of MDM2 has been
      shown to drastically impair MDM2 interaction with RPL11 and thus escapes the
      inhibition by this ribosomal protein, it still remains elusive whether RPL11
      inactivates MDM2 via direct action on this zinc finger domain and what is the
      chemical nature of this specific interaction. To define the roles of the MDM2
      zinc finger in association with RPL11, we conducted hydrogen-deuterium exchange
      mass spectrometry, computational modeling, circular dichroism, and mutational
      analyses of the zinc finger domain of MDM2 and human RPL11. Our study reveals
      that RPL11 forms a stable complex with MDM2 in vitro through direct contact with
      its zinc finger. This binding is disrupted by single mutations of non-cysteine
      amino acids within the zinc finger domain of MDM2. Basic residues in RPL11 are
      crucial for the stable binding and RPL11 suppression of MDM2 activity toward p53.
      These results provide the first line of evidence for the specific interaction
      between RPL11 and the zinc finger of MDM2 via hydrophilic residues as well as a
      molecular foundation for better understanding RPL11 inhibition of MDM2 function.

PMID- 21903594
TI  - Depression of release by mGluR8 alters Ca2+ dependence of release machinery.
AB  - The ubiquitous presynaptic metabotropic glutamate receptors (mGluRs) are
      generally believed to primarily inhibit synaptic transmission through blockade of
      Ca(2+) entry. Here, we analyzed how mGluR8 achieves a nearly complete inhibition
      of glutamate release at hippocampal synapses. Surprisingly, presynaptic Ca(2+)
      imaging and miniature excitatory postsynaptic current recordings showed that
      mGluR8 acts without affecting Ca(2+) entry, diffusion, and buffering. We
      quantitatively compared the Ca(2+) dependence of the inhibition of release by
      mGluR8 with the inhibition by omega-conotoxin GVIA. These calculations suggest
      that the inhibition produced by mGluR8 may be explained by a decrease in the
      apparent Ca(2+) affinity of the release sensor and, to a smaller extent, by a
      reduction of the maximal release rate. Upon activation of mGluR8, phasic
      transmitter release toward the end of a train of action potentials is greater as
      compared with presynaptic inhibition induced by blocking Ca(2+) entry, which is
      consistent with the important role of Ca(2+) in accelerating the replenishment of
      released vesicles. The action of mGluR8 was resistant to blockers of classical G
      protein transduction pathways including inhibition of adenylate cyclase and may
      represent a direct effect on the release machinery. In conclusion, our data
      identify a mode of presynaptic inhibition which allows mGluR8 to profoundly
      inhibit vesicle fusion while not diminishing vesicle replenishment and which
      thereby differentially changes the temporal transmission properties of the
      inhibited synapse.

PMID- 21903596
TI  - Opportunistic infections in paediatric inflammatory bowel disease patients.

PMID- 21903597
TI  - Association of paediatric inflammatory bowel disease with other immune-mediated
      diseases.
AB  - BACKGROUND: Associations between inflammatory bowel diseases (IBDs) and other
      immune-mediated diseases have been described in adult populations. Whether such
      associations exist in childhood-onset disease remains unknown. OBJECTIVES: The
      authors sought to evaluate whether paediatric IBD is associated with the
      occurrence of other immune-mediated diseases. STUDY DESIGN: The authors
      identified cases of Crohn's disease (CD) and ulcerative colitis (UC), <=20 years
      of age, using administrative data from 87 health plans. Each case was matched to
      three controls, on the basis of age, gender, and geographical region. The authors
      used logistic regression to compare the prevalence of various immune-mediated
      diseases (identified by International Classification of Diseases, ninth revision
      codes) in cases versus controls. RESULTS: The study included 737 children with CD
      (1997 controls) and 488 with UC (1310 controls). CD was associated with a higher
      prevalence of rheumatoid arthritis (OR 15.7, 95% CI 4.6 to 53.7), lupus (OR 41.0,
      95% CI 2.3 to 719.1) and hypothyroidism (OR 2.9, 95% CI 1.4 to 6.1), with a trend
      toward an increased prevalence of asthma, eczema, allergic rhinitis and diabetes.
      UC was associated with a higher prevalence of diabetes (OR 2.7, 95% CI 1.1 to
      6.6), with a trend towards increased prevalence of asthma, eczema, allergic
      rhinitis, hypothyroidism, rheumatoid arthritis and lupus. DISCUSSION: Children
      with IBD, particularly CD, have an elevated risk for immune-mediated conditions.
      This comorbidity adds to the burden of paediatric IBD, and suggests common
      aetiologic mechanisms.

PMID- 21903598
TI  - An unusual complication of foetal blood sampling.

PMID- 21903599
TI  - What causes attention deficit hyperactivity disorder?
AB  - Attention deficit hyperactivity disorder (ADHD) affects around 1-3% of children.
      There is a high level of comorbidity with developmental and learning problems as
      well as with a variety of psychiatric disorders. ADHD is highly heritable,
      although there is no single causal risk factor and non-inherited factors also
      contribute to its aetiology. The genetic and environmental risk factors that have
      been implicated appear to be associated with a range of neurodevelopmental and
      neuropsychiatric outcomes, not just ADHD. The evidence to date suggests that both
      rare and multiple common genetic variants likely contribute to ADHD and modify
      its phenotype. ADHD or a similar phenotype also appears to be more common in
      extreme low birth weight and premature children and those exposed to exceptional
      early adversity. In this review, the authors consider recent developments in the
      understanding of risk factors that influence ADHD.

PMID- 21903600
TI  - Recurrent faints due to asystole in an adolescent boy.

PMID- 21903601
TI  - Pediculosis causing iron deficiency anaemia in school children.

PMID- 21903602
TI  - Kawasaki disease as a cause of encephalitis.

PMID- 21903603
TI  - Outcome of surgical complications following simultaneous pancreas-kidney
      transplantation.
AB  - BACKGROUND: Simultaneous pancreas-kidney (SPK) transplantation carries a higher
      risk of surgical complications than kidney transplantation alone. We aimed to
      establish the incidence of surgical complications after SPK transplantation and
      determine the effect on graft and patient survival. METHODS: Outcomes of all SPK
      transplants performed at our centre were compared between patients who
      experienced a surgical complication (SC group) and those who did not (NSC group).
      RESULTS: Our centre performed 193 SPK transplants in a 15-year period; 44
      patients (23%) experienced a surgical complication. One-year and 5-year
      pancreatic graft survival was 89 and 80%, respectively; this was lower in the SC
      group. There was no significant difference in patient or kidney graft survival
      between the SC and NSC groups at 5 years (92 and 83%, respectively.) CONCLUSION:
      Surgical complications following SPK transplantation can cause significant
      morbidity and adversely affect pancreas graft survival, but do not affect long
      term kidney or patient survival.

PMID- 21903604
TI  - High prevalence of vertebral fractures in women with breast cancer starting
      aromatase inhibitor therapy.
AB  - BACKGROUND: The purpose of this study was to describe bone status in a large
      cohort of postmenopausal women with nonmetastatic breast cancer, at the
      initiation of aromatase inhibitor therapy. PATIENTS AND METHODS: A prospective,
      transversal and clinical study was conducted. Each woman had an extensive medical
      history, a biological evaluation, a bone mineral density (BMD) measurement and
      spinal X-rays. RESULTS: Four hundred and ninety-seven women aged 63.8 +/- 9.6
      years were included in this study. Eighty-five percent of these women had a 25-OH
      vitamin D concentration <75 nmol/l. One hundred and fifty-six women (31.4%) had a
      T-score < -2 at one of the three site measurements. Ninety-five women (19.1%) had
      a history of nonvertebral fracture with a total of 120 fractures. Spine X-rays
      evaluation revealed that 20% of the women had at least one vertebral fracture.
      The presence of vertebral fracture was associated with nonvertebral fracture
      history [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.1-2.4] and with
      spine BMD (OR 1.4, 95% CI 1.1-1.7). The prevalence of vertebral fracture reached
      62.9% in women with age above 70 years and femoral T-score < -2.5. CONCLUSION:
      Before starting aromatase inhibitor therapy for breast cancer, a large proportion
      of women had a vitamin D insufficiency and vertebral fractures.

PMID- 21903605
TI  - Phase II study of eribulin mesylate (E7389) in patients with metastatic
      castration-resistant prostate cancer stratified by prior taxane therapy.
AB  - BACKGROUND: Treatment options remain limited for patients with castration
      resistant prostate cancer (CRPC). We evaluated eribulin mesylate (E7389), a
      nontaxane halichondrin B analog microtubule inhibitor, in patients with
      metastatic CRPC with or without previous taxane exposure. PATIENTS AND METHODS:
      Men with histologically proven CRPC, with or without prior taxane exposure, were
      enrolled in an open-label, single-arm phase II trial. Patients received eribulin
      mesylate 1.4 mg/m(2) as a 2- to 5-min i.v. bolus infusion on days 1 and 8 of a 21
      day cycle. The primary efficacy end point was prostate-specific antigen (PSA)
      response rate. RESULTS: In total, 108 patients were assessable for safety (50
      were taxane-pretreated) and 105 for efficacy in the per-protocol population. The
      median age of patients was 71 years and median number of cycles was 4. PSA
      decreases of >= 50% were achieved in 22.4% and 8.5% of taxane-naive and taxane
      pretreated patients, respectively. The most common grade 3/4 adverse event was
      neutropenia, seen in 22.4% of chemo-naive and 40% of taxane-pretreated men. Grade
      3 peripheral neuropathy occurred in none of the taxane-naive patients and 6.0% of
      taxane-pretreated patients. CONCLUSION: Eribulin mesylate demonstrated activity
      and a relatively favorable toxicity profile in metastatic CRPC.

PMID- 21903606
TI  - Inhibition of focal adhesion kinase by PF-562,271 inhibits the growth and
      metastasis of pancreatic cancer concomitant with altering the tumor
      microenvironment.
AB  - Current therapies for pancreatic ductal adenocarcinoma (PDA) target individual
      tumor cells. Focal adhesion kinase (FAK) is activated in PDA, and levels are
      inversely associated with survival. We investigated the effects of PF-562,271 (a
      small-molecule inhibitor of FAK/PYK2) on (i) in vitro migration, invasion, and
      proliferation; (ii) tumor proliferation, invasion, and metastasis in a murine
      model; and (iii) stromal cell composition in the PDA microenvironment. Migration
      assays were conducted to assess tumor and stromal cell migration in response to
      cellular factors, collagen, and the effects of PF-562,271. An orthotopic murine
      model was used to assess the effects of PF-562,271 on tumor growth, invasion, and
      metastasis. Proliferation assays measured PF-562,271 effects on in vitro growth.
      Immunohistochemistry was used to examine the effects of FAK inhibition on the
      cellular composition of the tumor microenvironment. FAK and PYK2 were activated
      and expressed in patient-derived PDA tumors, stromal components, and human PDA
      cell lines. PF-562,271 blocked phosphorylation of FAK (phospho-FAK or Y397) in a
      dose-dependent manner. PF-562,271 inhibited migration of tumor cells, cancer
      associated fibroblasts, and macrophages. Treatment of mice with PF-562,271
      resulted in reduced tumor growth, invasion, and metastases. PF-562,271 had no
      effect on tumor necrosis, angiogenesis, or apoptosis, but it did decrease tumor
      cell proliferation and resulted in fewer tumor-associated macrophages and
      fibroblasts than control or gemcitabine. These data support a role for FAK in PDA
      and suggest that inhibitors of FAK may contribute to efficacious treatment of
      patients with PDA.

PMID- 21903607
TI  - Tasisulam sodium, an antitumor agent that inhibits mitotic progression and
      induces vascular normalization.
AB  - LY573636-sodium (tasisulam) is a small molecule antitumor agent with a novel
      mechanism of action currently being investigated in a variety of human cancers.
      In vitro, tasisulam induced apoptosis via the intrinsic pathway, resulting in
      cytochrome c release and caspase-dependent cell death. Using high content
      cellular imaging and subpopulation analysis of a wide range of in vitro and in
      vivo cancer models, tasisulam increased the proportion of cells with 4N DNA
      content and phospho-histone H3 expression, leading to G(2)-M accumulation and
      subsequent apoptosis. Tasisulam also blocked VEGF, epidermal growth factor, and
      fibroblast growth factor-induced endothelial cell cord formation but did not
      block acute growth factor receptor signaling (unlike sunitinib, which blocks VEGF
      driven angiogenesis at the receptor kinase level) or induce apoptosis in primary
      endothelial cells. Importantly, in vivo phenocopying of in vitro effects were
      observed in multiple human tumor xenografts. Tasisulam was as effective as
      sunitinib at inhibiting neovascularization in a Matrigel plug angiogenesis assay
      in vivo and also caused reversible, non G(2)-M-dependent growth arrest in primary
      endothelial cells. Tasisulam also induced vascular normalization in vivo.
      Interestingly, the combination of tasisulam and sunitinib significantly delayed
      growth of the Caki-1 renal cell carcinoma model, whereas neither agent was active
      alone. These data show that tasisulam has a unique, dual-faceted mechanism of
      action involving mitotic catastrophe and antiangiogenesis, a phenotype distinct
      from conventional chemotherapies and published anticancer agents.

PMID- 21903608
TI  - Combining curcumin (diferuloylmethane) and heat shock protein inhibition for
      neurofibromatosis 2 treatment: analysis of response and resistance pathways.
AB  - Neurofibromatosis type 2 (NF2) is a genetic condition characterized by
      inactivation of the NF2 tumor suppressor gene and the development of schwannomas.
      The NF2 gene product, merlin, is activated (dephosphorylated) by contact
      inhibition and promotes growth suppression. We investigated the effect of
      curcumin (diferuloylmethane), a molecule with anti-inflammatory and
      antitumorigenic properties, on human schwannoma cell growth and the regulation of
      merlin by curcumin in both NF2 cells and neuroblastoma (non-NF2) cells. Curcumin
      inhibited the growth of HEI-193 schwannoma cells in vitro and downregulated the
      phosphorylation of Akt and extracellular signal-regulated kinase 1/2. Curcumin
      also activated MYPT1-pp1delta (a merlin phosphatase), which was associated with
      dephosphorylation of merlin on serine 518, an event that results in the folding
      of merlin to its active conformation. In addition, curcumin induced apoptosis and
      generated reactive oxygen species in HEI-193 cells. Consequently, hsp70 was
      upregulated at the mRNA and protein levels, possibly serving as a mechanism of
      escape from curcumin-induced apoptosis and growth inhibition. Endogenous merlin
      and hsp70 proteins interacted in HEI-193 schwannoma and SK-N-AS neuroblastoma
      cells. The combination of curcumin and an hsp inhibitor synergistically
      suppressed schwannoma cell growth. Our results provide a rationale for combining
      curcumin and KNK437 in the treatment of NF2.

PMID- 21903609
TI  - Micelle-encapsulated thiostrepton as an effective nanomedicine for inhibiting
      tumor growth and for suppressing FOXM1 in human xenografts.
AB  - The thiazole antiobiotic, thiostrepton, has been found to induce cell death in
      cancer cells through proteasome inhibition. As a proteasome inhibitor,
      thiostrepton has also been shown to suppress the expression of FOXM1, the
      oncogenic forkhead transcription factor overexpressed in cancer cells. In this
      study, we explored the potential in vivo anticancer properties of thiostrepton,
      delivered through nanoparticle encapsulation to xenograft models of breast and
      liver cancer. We encapsulated thiostrepton into micelles assembled from
      amphiphilic lipid-PEG (polyethylene glycol) molecules, where thiostrepton is
      solubilized within the inner lipid compartment of the micelle. Upon assembly,
      hydrophobic thiostrepton molecules are solubilized into the lipid component of
      the micelle shell, formed through the self-assembly of amphipilic lipid-PEG
      molecules. Maximum accumulation of micelle-thiostrepton nanoparticles (100 nm in
      diameter, -16 mV in zeta potential) into tumors was found at 4 hours
      postadministration and was retained for at least 24 hours. Upon continuous
      treatment, we found that nanoparticle-encapsulated thiostrepton reduced tumor
      growth rates of MDA-MB-231 and HepG2 cancer xenografts. Furthermore, we show for
      the first time the in vivo suppression of the oncogenic FOXM1 after treatment
      with proteasome inhibitors. Immunoblotting and immunohistochemical staining also
      showed increased apoptosis in the treated tumors, as indicated by cleaved caspase
      3 expression. Our data suggest that the thiazole antibiotic/proteasome inhibitor
      thiostrepton, when formulated into nanoparticles, may be highly suited as a
      nanomedicine for treating human cancer.

PMID- 21903612
TI  - A new prognostic index centered on polypathological patients. The PROFUND index.

PMID- 21903611
TI  - Intrinsic association of widowhood with mortality in community-dwelling older
      women and men: findings from a prospective propensity-matched population study.
AB  - OBJECTIVES: Widowhood is associated with increased mortality. However, to what
      extent this association is independent of other risk factors remains unclear. In
      the current study, we used propensity score matching to design a study to examine
      the independent association of widowhood with outcomes in a balanced cohort of
      older adults in the United States. METHODS: We used public-use copies of the
      Cardiovascular Health Study data obtained from the National Heart, Lung, and
      Blood Institute. Of the 5,795 community-dwelling older men and women aged 65
      years and older in Cardiovascular Health Study, 3,820 were married and 1,436 were
      widows or widowers. Propensity scores for widowhood, estimated for each of the
      5,256 participants, were used to assemble a cohort of 819 pairs of widowed and
      married participants who were balanced on 74 baseline characteristics. The 1,638
      matched participants had a mean (+/- standard deviation) age of 75 (+/- 6) years,
      78% were women, and 16% African American. RESULTS: All-cause mortality occurred
      in 46% (374/819) and 51% (415/819) of matched married and widowed participants,
      respectively, during more than 11 years of median follow-up (hazard ratio
      associated with widowhood, 1.18; 95% confidence interval, 1.03-1.36; p = .018).
      Hazard ratios (95% confidence intervals) for cardiovascular and noncardiovascular
      mortalities were 1.07 (0.87-1.32; p = .517) and 1.28 (1.06-1.55; p = .011),
      respectively. Widowhood had no independent association with all-cause or heart
      failure hospitalization or incident cardiovascular events. CONCLUSIONS: Among
      community-dwelling older adults, widowhood was associated with increased
      mortality, which was independent of confounding by baseline characteristics and
      largely driven by an increased noncardiovascular mortality. Widowhood had no
      independent association with hospitalizations or incident cardiovascular events.

PMID- 21903614
TI  - Quality of life of nursing home residents with dementia: a comparison of
      perspectives of residents, family, and staff.
AB  - PURPOSE: Quality of Life (QoL) has become increasingly valued as a key outcome in
      dementia both in clinical practice and in research. This study compares the QoL
      of long-term residents with dementia as assessed by the individuals, their
      relatives, and their care staff. DESIGN AND METHODS: Data on residents with
      dementia were collected in 11 nursing homes. The Quality of Life-Alzheimer's
      Disease Scale (QOL-AD) residential version was directly applied to residents with
      dementia diagnosis and Mini-Mental State Examination scores under 27, randomly
      selected in each canter. Residents' QoL was further assessed from the perspective
      of some close relative and of some staff member. Altogether, 102 data sets from
      residents, 184 from relatives, and 197 from staff members were collected.
      RESULTS: The completion rate for the resident QOL-AD was 48.8%. Residents' QoL
      ratings were significantly higher than proxies' ratings. Proxy (i.e., family and
      staff) scores in the QOL-AD tended to correlate with each other and did not
      correlate with resident scores. IMPLICATIONS: Various sources of data provided
      different perspectives on resident's QoL. Each perspective is relatively
      independent and somewhat unique. In those patients with mild to moderate
      cognitive impairment, direct measures of QoL should be considered.

PMID- 21903615
TI  - "Learning about your residents": how assisted living residence medication aides
      decide to administer pro re nata medications to persons with dementia.
AB  - PURPOSE: This study identified how unlicensed staff members decide to administer
      medications prescribed pro re nata (PRN) to residents of assisted living (AL)
      settings designated for persons with dementia. Theories of knowledge, including
      explicit and implicit knowledge, discretion, and judgment, guided the analysis.
      DESIGN AND METHODS: Data were collected and analyzed using qualitative methods.
      The staff members responsible for medication administration were shadowed for 6
      consecutive days in three Oregon ALs. In-person interviews were conducted with 16
      staff members, and residents' medication records were reviewed. RESULTS:
      Medication aides' decisions to administer PRN medications were informed by
      resident request, interpretation of resident-specific actions, training and
      experience, and setting-specific practices. The theme, learning about your
      residents, was consistent across settings. IMPLICATIONS: By administering PRN
      medications, medication aides play an important role in the daily care and
      comfort of AL residents with dementia. Policy makers need information about
      whether to permit unlicensed staff to administer medications and the level of
      training to require. This research suggests that training should recognize the
      tacit knowledge of practicing medication aides. Despite the role that PRN
      medications can play in the daily comfort and well-being of AL residents, little
      is known about as-needed medications prescribed versus those actually used across
      settings; also needed is an understanding of how other health professionals are
      involved in treatment plans that include medications.

PMID- 21903616
TI  - PRICE needs updating, should we call the POLICE?

PMID- 21903617
TI  - Medical care delivery at the Inaugural Youth Olympic Games Singapore 2010.
AB  - CONTEXT: Mass gatherings such as the Youth Olympic Games require medical services
      for large populations with special needs specific to elite competitive youth
      athletes. The location of the Games in a heavily populated city with dispersed
      competition venues provides unique challenges. OBJECTIVE: To describe the
      planning and delivery of medical services and to provide data for future
      planning. SETTING: Singapore. One large multipurpose clinic was set up in the
      Games Village as well as medical posts at competitive venues for 26 sports for
      onsite coverage. PERIOD OF COVERAGE: 10 August 2010 to 28 August 2010.
      Participants A total of 1,337 medical encounters ranging from athletes to
      officials and volunteers who received medical care from a spectrum of medical
      professionals. MAJOR OUTCOME MEASURES: measures Number of cases attended to at
      the Games Village medical centres and the medical posts at the competition
      venues, utilisation of medical services, and the pattern of these injuries and
      referral patterns to hospitals. RESULTS: Medical encounters for non-athletes
      represented 40.9% of the total medical encounters. The rate of heat illnesses was
      low for athletes at 1.7% (N = 13). The total hospitalisation rate was low at 1.7%
      (n = 23). Utilisation of onsite pharmacy and physiotherapy services were high at
      45.2% (n = 887) and 37.8% (n = 743), respectively, of the encounters for all
      support services. CONCLUSION: The dispersed nature of the Games venues provided
      challenges to the organisation of medical cover for the participants. Organisers
      in future Games can make use of the data to plan for future Games of a similar
      nature.

PMID- 21903618
TI  - Predictors of change in sports participation in Latino and non-Latino children.
AB  - BACKGROUND: Few prospective studies have examined predictors of change in
      specific physical activity (PA) behaviours in different ethnic groups. PURPOSE:
      To assess predictors of change in sports participation in Latino and non-Latino 5
      8 year-old children in San Diego, California. METHODS: Average sports
      participation frequency (days/week) was assessed by validated parent-report at
      baseline (Nov 2006-May 2008) and 1 year later in 541 children (45.0% male, 41.1%
      Latino; mean +/- SD age: 6.6 +/- 0.7 years) taking part in an obesity prevention
      study (Project MOVE). Biological (sex, age, Body Mass Index z-score), socio
      cultural (ethnicity, income, care giver education), parental (PA rules, PA
      encouragement) and environmental factors (home PA equipment, PA location) were
      assessed at baseline. Associations between change in sports participation and
      potential predictors were studied using multilevel linear regression stratified
      by Latino ethnicity, adjusted for sex, baseline sport participation, study
      condition and recruitment area. RESULTS: Sports participation increased over 1
      year (mean change: +0.5 days; p<0.001) and change was similar for boys and girls
      (p=0.95), but Latino children showed a greater increase (p=0.03). The number of
      locations used for PA (p=0.024) and the total frequency of PA location use
      (p=0.018) were positively associated with increased sports participation among
      Latinos. No predictors were identified for non-Latino children. CONCLUSIONS: Only
      factors relating to PA location were identified as predictors of change in sports
      participation for Latino children. Interventions targeting specific PA behaviours
      such as sports participation may need to consider PA locations for Latino
      children and be tailored for specific ethnic groups.

PMID- 21903619
TI  - Suppression of information on the prevalence and prevention of exercise
      associated hyponatraemia.
AB  - It has been suggested recently that financial links between manufacturers of
      sports drinks and professional Sports Science organisations in North America have
      suppressed information on the existence and ways of preventing an epidemic of
      exercise-associated hyponatraemia (EAH). This article reviews evidence for the
      prevalence of both biochemical and clinical hyponatraemia. It concludes that a
      limited number of cases of EAH occur after ultra-long distance events,
      particularly when performed under cold and wet conditions, and that some eight
      deaths have been associated with EAH since 1985. However, this information has
      been widely reported, both in North America and in other parts of the world.
      Claims of an 'epidemic' seem unwarranted, and there is no solid evidence
      supporting the claim that information has been suppressed because of ties between
      sports scientists and sports drink manufacturers.

PMID- 21903620
TI  - Management of an apparent life-threatening event: a survey of emergency
      physicians practice.
AB  - OBJECTIVE: The etiology of an apparent life-threatening event (ALTE) has been
      attributed to a wide range of causes. Physicians rely on caregiver narratives,
      which are often unreliable given the distressing nature of the event, which in
      turn leads to variation in the evaluation and management. The objective of this
      study was to study this variation in the management of ALTE among emergency
      physicians in Michigan. DESIGN AND METHODS: The authors developed and conducted a
      survey that contained questions on the evaluation and management of 2 common ALTE
      scenarios. These surveys were then mailed to 1000 randomly selected emergency
      physicians from a comprehensive physician database. RESULTS: A total of 25.5%
      responded. Majority of the respondents were trained in emergency medicine
      residency. Fourth-seven percent of the respondents work in suburban areas. Most
      respondents said that they would perform diagnostic laboratory workup on children
      presenting with ALTE although there is wide variation in the extent of the
      workup. Ninety-two percent of ALTE patients are likely to get pediatric
      subspecialist consultation from the emergency department. CONCLUSIONS: There is a
      wide variation in the evaluation and management of ALTE among emergency medicine
      physicians in Michigan. These children with ALTE are very likely to be seen by
      pediatric subspecialists subsequently.

PMID- 21903621
TI  - Swaddling: will it get babies onto their backs for sleep?
AB  - INTRODUCTION: The supine sleep position is recommended to reduce sudden infant
      death syndrome risk. Swaddling may improve adherence with supine placement. AIM:
      To assess knowledge, attitudes, and practice regarding swaddling among adult
      caregivers of 0- to 3-month-old infants. METHODS: Cross-sectional descriptive
      survey. RESULTS: All 103 adults interviewed had swaddled their infant. Common
      reasons for swaddling included infant comfort and warmth. Almost 80% of those who
      swaddled their infant found it effective, 80% believed it to be comfortable, and
      ~90% believed swaddling to be safe. Parents who routinely used swaddling were
      more likely to find it effective and to place their infant supine when swaddled
      (P < .01). CONCLUSIONS: Parents often use swaddling to comfort the infant, and
      most find it effective. Parents who routinely use swaddling are more likely to
      place their infant supine if swaddled. Swaddling may be a strategy for parents of
      infants who have difficulty sleeping in the supine position.

PMID- 21903622
TI  - The pediatrician's guide to managing the difficult pediatric headache patient.
AB  - Pediatric headache is a common pain complaint in children and adolescents, and
      pediatricians are the first source of headache assessment and treatment. This
      article provides guidelines for pediatricians in managing difficult headache
      patients typically seen in our practice. The 3 categories we typically evaluates
      and treats include (a) "It's medical, not psychological"; (b) "You're the only
      doctor who can help me"; and (c) "My child is perfect." A brief case presentation
      illustrates each of these categories of patients. Specific recommendations for
      treatment, as well as guidelines for parents, are provided.

PMID- 21903623
TI  - Parental perspectives of early childhood caries.
AB  - BACKGROUND. Parental perspectives of children with early childhood caries may
      help inform the development and improvement of caries prevention strategies.
      OBJECTIVES. This study aimed to explore parents' experiences, perceptions, and
      expectations regarding prevention and management of early childhood caries.
      Methods. The authors conducted semistructured interviews with 25 parents of
      children aged 2 to 5 years, with a known history of caries. All interviews were
      transcribed and coded, and iterative analyses were conducted to identify key
      emergent themes within the data. RESULTS. Parents had limited knowledge of
      behaviors contributing to early childhood caries and when to first seek regular
      dental care. Parents expected pediatricians to provide education on how to
      prevent childhood caries, conduct preliminary oral health assessments, and help
      establish early linkages between medical and dental care. CONCLUSION. The
      findings make a strong case for pediatricians to take responsibility for engaging
      and educating parents on fostering optimal oral health and helping to access
      early childhood dental care.

PMID- 21903624
TI  - Finding stable local optimal RNA secondary structures.
AB  - MOTIVATION: Many RNAs, such as riboswitches, can fold into multiple alternate
      structures and perform different biological functions. These biologically
      functional structures usually have low free energies in their local energy
      landscapes and are very stable such that they cannot easily jump out of the
      current states and fold into other stable conformations. The conformational space
      of feasible RNA secondary structures is prohibitively large, and accurate
      prediction of functional structure conformations is challenging. Because the
      stability of an RNA secondary structure is determined predominantly by
      energetically favorable helical regions (stacks), we propose to use
      configurations of putative stacks to represent RNA secondary structures. By
      considering a reduced conformational space of local optimal stack configurations
      instead of all feasible RNA structures, we first present an algorithm for
      enumerating all possible local optimal stack configurations. In addition, we
      present a fast heuristic algorithm for approximating energy barriers encountered
      during folding pathways between each pair of local optimal stack configurations
      and finding all the stable local optimal structures. RESULTS: Benchmark tests
      have been conducted on several RNA riboswitches, whose alternate secondary
      structures have been experimentally verified. The benchmark results show that our
      method can successfully predict the native 'on' and 'off' secondary structures,
      and better rank them compared with other state-of-art approaches. AVAILABILITY:
      The software is freely available and can be downloaded at
      http://genome.ucf.edu/RNASLOpt. CONTACT: shzhang@eecs.ucf.edu. SUPPLEMENTARY
      INFORMATION: Supplementary data are available at Bioinformatics online.

PMID- 21903625
TI  - Comparing bioassay response and similarity ensemble approaches to probing protein
      pharmacology.
AB  - MOTIVATION: Networks to predict protein pharmacology can be created using ligand
      similarity or using known bioassay response profiles of ligands. Recent
      publications indicate that similarity methods can be highly accurate, but it has
      been unclear how similarity methods compare to methods that use bioassay response
      data directly. RESULTS: We created protein networks based on ligand similarity
      (Similarity Ensemble Approach or SEA) and ligand bioassay response-data (BARD)
      using 155 Pfizer internal BioPrint assays. Both SEA and BARD successfully cluster
      together proteins with known relationships, and predict some non-obvious
      relationships. Although the approaches assess target relations from different
      perspectives, their networks overlap considerably (40% overlap of the top 2% of
      correlated edges). They can thus be considered as comparable methods, with a
      distinct advantage of the similarity methods that they only require simple
      computations (similarity of compound) as opposed to extensive experimental data.
      CONTACTS: djwild@indiana.edu; eric.gifford@pfizer.com. SUPPLEMENTARY INFORMATION:
      Supplementary data are available at Bioinformatics online.

PMID- 21903626
TI  - TopiaryExplorer: visualizing large phylogenetic trees with environmental
      metadata.
AB  - MOTIVATION: Microbial community profiling is a highly active area of research,
      but tools that facilitate visualization of phylogenetic trees and associated
      environmental data have not kept up with the increasing quantity of data
      generated in these studies. RESULTS: TopiaryExplorer supports the visualization
      of very large phylogenetic trees, including features such as the automated
      coloring of branches by environmental data, manipulation of trees and
      incorporation of per-tip metadata (e.g. taxonomic labels). AVAILABILITY:
      http://topiaryexplorer.sourceforge.net. CONTACT: rob.knight@colorado.edu.

PMID- 21903627
TI  - A statistical framework for SNP calling, mutation discovery, association mapping
      and population genetical parameter estimation from sequencing data.
AB  - MOTIVATION: Most existing methods for DNA sequence analysis rely on accurate
      sequences or genotypes. However, in applications of the next-generation
      sequencing (NGS), accurate genotypes may not be easily obtained (e.g. multi
      sample low-coverage sequencing or somatic mutation discovery). These applications
      press for the development of new methods for analyzing sequence data with
      uncertainty. RESULTS: We present a statistical framework for calling SNPs,
      discovering somatic mutations, inferring population genetical parameters and
      performing association tests directly based on sequencing data without explicit
      genotyping or linkage-based imputation. On real data, we demonstrate that our
      method achieves comparable accuracy to alternative methods for estimating site
      allele count, for inferring allele frequency spectrum and for association
      mapping. We also highlight the necessity of using symmetric datasets for finding
      somatic mutations and confirm that for discovering rare events, mismapping is
      frequently the leading source of errors. AVAILABILITY:
      http://samtools.sourceforge.net. CONTACT: hengli@broadinstitute.org.

PMID- 21903628
TI  - An empirical comparison of several recent epistatic interaction detection
      methods.
AB  - MOTIVATION: Many new methods have recently been proposed for detecting epistatic
      interactions in GWAS data. There is, however, no in-depth independent comparison
      of these methods yet. RESULTS: Five recent methods-TEAM, BOOST, SNPHarvester,
      SNPRuler and Screen and Clean (SC)-are evaluated here in terms of power, type-1
      error rate, scalability and completeness. In terms of power, TEAM performs best
      on data with main effect and BOOST performs best on data without main effect. In
      terms of type-1 error rate, TEAM and BOOST have higher type-1 error rates than
      SNPRuler and SNPHarvester. SC does not control type-1 error rate well. In terms
      of scalability, we tested the five methods using a dataset with 100 000 SNPs on a
      64 bit Ubuntu system, with Intel (R) Xeon(R) CPU 2.66 GHz, 16 GB memory. TEAM
      takes ~36 days to finish and SNPRuler reports heap allocation problems. BOOST
      scales up to 100 000 SNPs and the cost is much lower than that of TEAM. SC and
      SNPHarvester are the most scalable. In terms of completeness, we study how
      frequently the pruning techniques employed by these methods incorrectly prune
      away the most significant epistatic interactions. We find that, on average, 20%
      of datasets without main effect and 60% of datasets with main effect are pruned
      incorrectly by BOOST, SNPRuler and SNPHarvester. AVAILABILITY: The software for
      the five methods tested are available from the URLs below. TEAM:
      http://csbio.unc.edu/epistasis/download.php BOOST:
      http://ihome.ust.hk/~eeyang/papers.html. SNPHarvester:
      http://bioinformatics.ust.hk/SNPHarvester.html. SNPRuler:
      http://bioinformatics.ust.hk/SNPRuler.zip. Screen and Clean:
      http://wpicr.wpic.pitt.edu/WPICCompGen/. CONTACT: wangyue@nus.edu.sg.

PMID- 21903629
TI  - FLASH: fast length adjustment of short reads to improve genome assemblies.
AB  - MOTIVATION: Next-generation sequencing technologies generate very large numbers
      of short reads. Even with very deep genome coverage, short read lengths cause
      problems in de novo assemblies. The use of paired-end libraries with a fragment
      size shorter than twice the read length provides an opportunity to generate much
      longer reads by overlapping and merging read pairs before assembling a genome.
      RESULTS: We present FLASH, a fast computational tool to extend the length of
      short reads by overlapping paired-end reads from fragment libraries that are
      sufficiently short. We tested the correctness of the tool on one million
      simulated read pairs, and we then applied it as a pre-processor for genome
      assemblies of Illumina reads from the bacterium Staphylococcus aureus and human
      chromosome 14. FLASH correctly extended and merged reads >99% of the time on
      simulated reads with an error rate of <1%. With adequately set parameters, FLASH
      correctly merged reads over 90% of the time even when the reads contained up to
      5% errors. When FLASH was used to extend reads prior to assembly, the resulting
      assemblies had substantially greater N50 lengths for both contigs and scaffolds.
      AVAILABILITY AND IMPLEMENTATION: The FLASH system is implemented in C and is
      freely available as open-source code at http://www.cbcb.umd.edu/software/flash.
      CONTACT: t.magoc@gmail.com.

PMID- 21903630
TI  - survcomp: an R/Bioconductor package for performance assessment and comparison of
      survival models.
AB  - SUMMARY: The survcomp package provides functions to assess and statistically
      compare the performance of survival/risk prediction models. It implements state
      of-the-art statistics to (i) measure the performance of risk prediction models;
      (ii) combine these statistical estimates from multiple datasets using a meta
      analytical framework; and (iii) statistically compare the performance of
      competitive models.

PMID- 21903631
TI  - Reconstructing transcription factor activities in hierarchical transcription
      network motifs.
AB  - MOTIVATION: A knowledge of the dynamics of transcription factors is fundamental
      to understand the transcriptional regulation mechanism. Nowadays, an experimental
      measure of transcription factor activities in vivo represents a challenge.
      Several methods have been developed to infer these activities from easily
      measurable quantities such as mRNA expression of target genes. A limitation of
      these methods is represented by the fact that they rely on very simple single
      layer structures, typically consisting of one or more transcription factors
      regulating a number of target genes. RESULTS: We present a novel statistical
      inference methodology to reverse engineer the dynamics of transcription factors
      in hierarchical network motifs such as feed-forward loops. The approach we
      present is based on a continuous time representation of the system where the high
      level master transcription factor is represented as a two state Markov jump
      process driving a system of differential equations. We solve the inference
      problem using an efficient variational approach and demonstrate our method on
      simulated data and two real datasets. The results on real data show that the
      predictions of our approach can capture biological behaviours in a more effective
      way than single-layer models of transcription, and can lead to novel biological
      insights. AVAILABILITY: http://homepages.inf.ed.ac.uk/gsanguin/software.html
      CONTACT: g.sanguinetti@ed.ac.uk SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 21903632
TI  - Protein-protein binding affinity prediction on a diverse set of structures.
AB  - MOTIVATION: Accurate binding free energy functions for protein-protein
      interactions are imperative for a wide range of purposes. Their construction is
      predicated upon ascertaining the factors that influence binding and their
      relative importance. A recent benchmark of binding affinities has allowed, for
      the first time, the evaluation and construction of binding free energy models
      using a diverse set of complexes, and a systematic assessment of our ability to
      model the energetics of conformational changes. RESULTS: We construct a large set
      of molecular descriptors using commonly available tools, introducing the use of
      energetic factors associated with conformational changes and disorder to order
      transitions, as well as features calculated on structural ensembles. The
      descriptors are used to train and test a binding free energy model using a
      consensus of four machine learning algorithms, whose performance constitutes a
      significant improvement over the other state of the art empirical free energy
      functions tested. The internal workings of the learners show how the descriptors
      are used, illuminating the determinants of protein-protein binding. AVAILABILITY:
      The molecular descriptor set and descriptor values for all complexes are
      available in the Supplementary Material. A web server for the learners and
      coordinates for the bound and unbound structures can be accessed from the
      website: http://bmm.cancerresearchuk.org/~Affinity. CONTACT:
      paul.bates@cancer.org.uk. SUPPLEMENTARY INFORMATION: Supplementary data are
      available at Bioinformatics online.

PMID- 21903633
TI  - Integrative cancer genomics (IntOGen) in Biomart.
AB  - Recently, we created IntOGen, a resource to integrate a large amount of cancer
      genomic data. IntOGen aims at facilitating the detection of the most recurrent
      alterations that drive tumorigenesis. It collates, annotates and analyzes high
      throughput data about transcriptional, genomic and mutational changes taking
      place in tumors from different studies annotated with specific cancer types.
      Currently, it contains 118 studies for mRNA expression profiling and 188 studies
      for genomic alterations covering in total 64 different tumor topographies. In
      this article, we describe the Biomart portal for IntOGen. The portal provides
      easy access to different types of data and facilitates the bulk download of all
      the analysis results. Here, we describe the general features of IntOGen and give
      example queries to demonstrate its use. Database URL: www.intogen.org.

PMID- 21903634
TI  - The injured and regenerating nervous system: immunoglobulin superfamily members
      as key players.
AB  - Understanding restricted functional recovery and designing efficient treatments
      to alleviate dysfunction after injury of the nervous system remain major
      challenges in neuroscience and medicine. Numerous molecules of potential
      significance in neural repair have been identified in vitro, but only few of
      these have proved to be of major importance in vivo up to now. Among the
      molecules involved in regeneration are several members of the immunoglobulin
      superfamily, most notably the neural cell adhesion molecules L1, its close
      homologue CHL1, and NCAM and, in particular, its polysialic acid glycan moiety.
      Sufficient evidence is now available to justify the statement that these
      molecules are major players not only in nervous system development but also in
      the adult during neural repair and synaptic plasticity. Importantly, insights
      into the functions of these molecules in promoting or inhibiting functional
      recovery have allowed the design and assessment of therapeutic approaches in
      animal models of central nervous system injury that could prove to be applicable
      in clinical settings.

PMID- 21903635
TI  - Antiviral protection mechanisms mediated by ginbuna crucian carp interferon gamma
      isoforms 1 and 2 through two distinct interferon gamma-receptors.
AB  - Fish genomes possess three type II interferon (IFN) genes, ifngamma1, ifngamma2
      and ifngamma-related (ifngammarel). The IFNgamma-dependent STAT signalling
      pathway found in humans and mice had not been characterized in fish previously.
      To identify the antiviral functions and signalling pathways of the type II IFN
      system in fish, we purified the ifngamma1, ifngamma2 and ifngammarel proteins of
      ginbuna crucian carp expressed in bacteria and found them to elicit high
      antiviral activities against crucian carp hematopoietic necrosis virus. We also
      cloned two distinct ifngamma receptor alpha chain (ifngr1) isoforms, 1 and 2, and
      stably expressed them in HeLa cells by transfecting the cells with ifngr1-1 or
      ifngr1-2 cDNA. When receptor transfectants were treated with the ligands in a one
      ligand-one-receptor manner (ifngamma1 and ifngr1-2 or ifngamma2 and ifngr1-1),
      the stat1 protein was phosphorylated at both serine-727 and tyrosine-701
      residues. Gel shift mobility analysis and reporter assay clearly showed that the
      specific ligand-receptor interaction resulted in the binding of the stat1 protein
      to the GAS element and enhanced transcription. Therefore, the actions of
      ifngamma1 and ifngamma2 were found to be mediated by a specific receptor for each
      signalling pathway via a stat1-dependent mechanism.

PMID- 21903636
TI  - Establishment and characterization of hepatocytes from an Immortomouse/SMP30/GNL
      knockout mouse hybrid lacking vitamin C to study vitamin C transport.
AB  - Senescence marker protein-30 (SMP30) has been identified as the lactone
      hydrolysing enzyme gluconolactonase (GNL), which is involved in vitamin C (L
      ascorbic acid, AA) biosynthesis. We previously reported the development of
      SMP30/GNL knockout (KO) mice unable to synthesize AA in vivo. For more efficient
      study of the liver's AA uptake and as yet uncharacterized efflux system, we
      established an immortal hepatocyte line derived from a hybrid of SMP30/GNL KO
      mice and Immortomice. Immortomice express the thermolabile simian virus 40 (SV40)
      large T antigen tsA58. These SMP30/GNL KO immortal hepatocytes proliferate at the
      permissive temperature of 33 degrees C but degrade rapidly at the non-permissive
      temperature of 39 degrees C. Additionally, they are SMP30-/GNL-deficient, express
      SV40 large T antigen and proliferate steadily at 33 degrees C. However, the
      cells' proliferation is arrested at 39 degrees C. A phase contrast micrograph
      revealed that the cells are binucleated with an enlarged cytoplasm similar to
      that of primary cultured hepatocytes from wild-type mice. Dose-response and time
      dependent study of AA uptake revealed that the cells, although unable to
      synthesize AA, took up AA from the culture medium. This property of our SMP30/GNL
      immortal hepatocytes makes them extremely useful for studying AA uptake and
      efflux systems in the liver.

PMID- 21903637
TI  - Allogeneic adipose-derived stem cells suppress Th17 lymphocytes in patients with
      active lupus in vitro.
AB  - Interleukin-17 (IL-17)-producing CD4(+) T cells (Th17 cells) have been proven to
      play a critical role in the pathogenesis of systemic lupus erythematosus (SLE).
      To shed light on the mechanism of immunoregulation of adipose-derived stem cells
      (ADSCs), we investigated the effects of allogeneic ADSCs on the Th17 lymphocytes
      of patients with active SLE by co-culturing ADSCs and peripheral blood
      mononuclear cells of these patients in vitro. The results indicated that ADSCs
      from passage 3 (P3) down-regulated the proportion of Th17 cells and their
      abilities to produce IL-17, whereas ADSCs from passage 8 (P8) had contrasting
      effect. The results also showed cell-cell contact played a role in P3 down
      regulation. Blocking the functional pathway of IL-23 (both its ligand and its
      receptor) also contributed to this suppression. These results suggested that
      immunomodulation of ADSCs may be achieved by partially suppressing the number and
      capability of Th17 lymphocytes, indicating that ADSCs could be employed as
      therapeutic tools for the autoimmune diseases.

PMID- 21903638
TI  - Wnt/Ca2+ signaling pathway: a brief overview.
AB  - The non-canonical Wnt/Ca(2+) signaling cascade is less characterized than their
      canonical counterpart, the Wnt/beta-catenin pathway. The non-canonical Wnt
      signaling pathways are diverse, defined as planer cell polarity pathway, Wnt-RAP1
      signaling pathway, Wnt-Ror2 signaling pathway, Wnt-PKA pathway, Wnt-GSK3MT
      pathway, Wnt-aPKC pathway, Wnt-RYK pathway, Wnt-mTOR pathway, and Wnt/calcium
      signaling pathway. All these pathways exhibit a considerable degree of overlap
      between them. The Wnt/Ca(2+) signaling pathway was deciphered as a crucial
      mediator in development. However, now there is substantial evidence that the
      signaling cascade is involved in many other molecular phenomena. Many aspects of
      Wnt/Ca(2+) pathway are yet enigmatic. This review will give a brief overview of
      the fundamental and evolving concepts of the Wnt/Ca(2+) signaling pathway.

PMID- 21903639
TI  - Carcinoid syndrome from small bowel endocrine carcinoma in the absence of hepatic
      metastasis.
AB  - An 80-year-old male patient presented with abdominal pain, paroxysmal
      diaphoresis, diarrhoea and vomiting. CT scan revealed a small bowel endocrine
      carcinoma (or 'carcinoid' tumour), but the absence of hepatic disease. The lesion
      was excised 'en-bloc'. Intra-operatively, there was wide fluctuation in blood
      pressure associated with tumour manipulation, with hyper- and hypotension.
      Carcinoid syndrome usually occurs from gastrointestinal tumours when hepatic
      metastases occur, causing flushing, diarrhoea, bronchoconstriction and murmurs
      from cardiac valvular lesions. This patient did not have radiological evidence of
      hepatic metastasis, but the syndrome could still occur with midgut tumours via
      local invasion of the retroperitoneal circulation, or by action of substances
      other than serotonin that do not undergo hepatic metabolism.

PMID- 21903640
TI  - Increase of paradoxical excitement response during propofol-induced sedation in
      hazardous and harmful alcohol drinkers.
AB  - BACKGROUND: Paradoxical excitement response during sedation consists of loss of
      affective control and abnormal movements. Chronic alcohol abuse has been proposed
      as a predisposing factor despite lack of supporting evidence. Because alcohol and
      propofol have a common site of action, we postulated that paradoxical excitement
      responses during propofol-induced sedation occur more frequently in hazardous and
      harmful alcohol drinkers than in social or non-drinkers. METHODS: One hundred and
      ninety patients undergoing orthopaedic knee joint surgery were enrolled in this
      prospective and observational study. Subjects were divided into Group HD
      (hazardous and harmful drinkers) or Group NHD (no hazardous drinkers) according
      to the alcohol use disorder identification test (AUDIT). In study 1, propofol
      infusion was adjusted to achieve the bispectral index at 70-80 using target
      controlled infusion. In study 2, the target concentration of propofol was fixed
      at 0.8 (study 2/Low) or 1.4 MUg ml(-1) (study 2/High). Paradoxical excitement
      responses were categorized by intensity into mild, moderate, or severe. RESULTS:
      The overall incidence of paradoxical excitement response was higher in Group HD
      than in Group NHD in study 1 (71.4% vs 43.8%; P=0.022) and study 2/High (70.0% vs
      34.5%; P=0.006) but not in study 2/Low. The incidence of moderate-to-severe
      response was significantly higher in Group HD of study 1 (28.6% vs 3.1%;
      P=0.0005) and study 2/High (23.3% vs 3.4%; P=0.029) with no difference in study
      2/Low. Severe excitement response occurred only in Group HD of study 1 and study
      2/High. CONCLUSIONS: Paradoxical excitement occurred more frequently and severely
      in hazardous and harmful alcohol drinkers than in social drinkers during propofol
      induced moderate-to-deep sedation, but not during light sedation.

PMID- 21903642
TI  - Learning through high-fidelity anaesthetic simulation: the role of episodic
      memory.

PMID- 21903643
TI  - Local infiltration analgesia for total knee arthroplasty.

PMID- 21903644
TI  - Royal Perth Hospital solution for managing the 'can't intubate, can't ventilate'
      crisis.

PMID- 21903646
TI  - Single-dose intravenous paracetamol or propacetamol for prevention or treatment
      of postoperative pain.

PMID- 21903648
TI  - Consent of subjects for general anaesthetic in Caesarean section.

PMID- 21903650
TI  - Tracheal intubation with the direct and indirect laryngoscopes in patients with
      cervical spine immobilization.

PMID- 21903652
TI  - Viable oxygenation with cannula-over-needle cricothyrotomy for asphyxial airway
      occlusion.

PMID- 21903653
TI  - The novel Kv1.5 channel blocker vernakalant for successful treatment of new-onset
      atrial fibrillation in a critically ill abdominal surgical patient.

PMID- 21903654
TI  - Xenon anaesthesia for laparoscopic cholecystectomy in a patient with multiple
      chemical sensitivity.

PMID- 21903655
TI  - Anaphylactic shock after sensitization to gelatin.

PMID- 21903656
TI  - A case for routine tonometry to avoid postoperative visual loss.

PMID- 21903657
TI  - Increased antibiotic use in Norwegian hospitals despite a low antibiotic
      resistance rate.
AB  - OBJECTIVES: Although antibiotic use and resistance are low in Norway, the
      situation risks changing for the worse. We investigated trends in antibiotic use
      and assessed them in relation to antibiotic resistance in Norway. METHODS: We
      drew on hospital pharmacy sales data to record antibiotic use from 2002 to 2007
      in eight hospitals serving 36% of the nation's population. Antibiotic use was
      measured using different indices with defined daily doses (DDDs) as the numerator
      (WHO ATC/DDD classification). RESULTS: Total antibiotic use increased from 1.02
      to 1.30 DDDs/1000 inhabitants/day (DIDs) and from 61.7 to 72.4 DDDs/100 bed-days
      (BDs) (17.4%); related to the number of discharges, no significant DDD change was
      shown. Their use in core units (adult intensive care units, recovery/post
      operative wards and departments of internal medicine and surgery with all
      subspecialties) increased from 64.1 to 80.8 DDDs/100 BDs (26.1%) and by 3.1%
      related to the number of discharges. The total use of broad-spectrum antibiotics
      increased by 47.9% when measured as DDDs/100 BDs, and by 19.1% based on the
      number of discharges; the corresponding figures for core units were 60.5% and
      31.2%, respectively. CONCLUSIONS: There was a substantial increase in total
      antibiotic use, and an even more pronounced increase in the use of broad-spectrum
      antibiotics, which seems unjustified considering the current low antibiotic
      resistance in Norway.

PMID- 21903658
TI  - Manuka honey inhibits cell division in methicillin-resistant Staphylococcus
      aureus.
AB  - OBJECTIVES: The aim of this study was to investigate the effect of manuka honey,
      artificial honey and an antibacterial component (methylglyoxal) on cell division
      in methicillin-resistant Staphylococcus aureus (MRSA). METHODS: Viability of
      epidemic MRSA-15 NCTC 13142 incubated with manuka honey, artificial honey and
      methylglyoxal was determined, and structural effects monitored by electron
      microscopy. Activity of murein hydrolase (a peptidoglycan-degrading enzyme
      implicated in cell separation, encoded by atl) was estimated by cell wall
      hydrolysis and zymography; expression of atl was quantified by real-time PCR.
      RESULTS: Growth of MRSA was inhibited by 5%, 10% and 20% (w/v) manuka honey and
      10% (w/v) artificial honey containing methylglyoxal, but not 10% (w/v) artificial
      honey. Statistically significantly increased numbers of cells containing septa
      and increased cell diameter (P < 0.001 and P < 0.001, respectively) were found in
      MRSA exposed to 5%, 10% or 20% (w/v) manuka honey, but not 10% (w/v) artificial
      honey with and without methylglyoxal. Intracellular activity of murein hydrolase
      was elevated in MRSA grown in 10% (w/v) artificial honey and at undetectable
      levels in MRSA treated with 10% (w/v) manuka honey. Increased atl expression was
      found in MRSA treated with 10% (w/v) manuka honey and 10% artificial honey
      containing methylglyoxal. CONCLUSIONS: Enlarged cells containing septa were
      observed in MRSA exposed to inhibitory concentrations of manuka honey, suggesting
      that cell division was interrupted. These changes were not caused by either the
      sugars or methylglyoxal in honey and indicate the presence of additional
      antibacterial components in manuka honey.

PMID- 21903659
TI  - Comment on: Successful treatment of methicillin-resistant Staphylococcus aureus
      mitral valve endocarditis with sequential linezolid and telavancin monotherapy
      following daptomycin failure.

PMID- 21903661
TI  - A fluoroquinolone-resistant Acinetobacter baumannii without the quinolone
      resistance-determining region mutations.

PMID- 21903660
TI  - Liver toxicity associated with antiretroviral therapy including efavirenz or
      ritonavir-boosted protease inhibitors in a cohort of HIV/hepatitis C virus co
      infected patients.
AB  - OBJECTIVES: To compare the frequency of grade 3 or 4 transaminase elevations
      (TEs) in HIV/hepatitis C virus (HCV) co-infected patients who started a three
      antiretroviral drug regimen including efavirenz or a ritonavir-boosted protease
      inhibitor (PI/r) and the influence of pre-existing significant hepatic fibrosis
      or cirrhosis. PATIENTS AND METHODS: All pre-treated or treatment-naive HIV/HCV co
      infected patients who started an antiretroviral regimen including two
      nucleos(t)ide reverse transcriptase inhibitors along with efavirenz or a PI/r in
      seven Spanish centres from January 2007 to December 2009 were included in this
      prospective study. RESULTS: Of 262 patients included in this study, 76 (29%)
      individuals began antiretroviral therapy (ART) including efavirenz and 186 (71%)
      a PI/r-based combination. The median (interquartile) follow-up was 14.0 (6.2
      23.7) months. A total of 20 (7.6%) patients presented grade 3-4 TEs. Four (1.5%)
      subjects discontinued ART due to this adverse event. Grade 3-4 TEs were observed
      in 5 (6.6%) subjects receiving efavirenz and 15 (8.1%) treated with PI/r (P =
      0.681). Three (6.5%) patients in the efavirenz group with significant fibrosis
      developed grade 3-4 TEs versus 2 (8.7%) without pre-existing significant fibrosis
      (P = 0.743). In the PI/r group, the corresponding figures were 10 (8.8%) and 5
      (9.3%), respectively (P = 0.931). CONCLUSIONS: The frequency of grade 3-4 TEs
      associated with efavirenz-based ART combinations under clinical practice
      conditions is low and similar to that found in patients receiving PI/r currently
      used in HIV/HCV co-infected patients. The baseline fibrosis stage does not have
      an impact on the development of TEs caused by these antiretroviral drugs in this
      population.

PMID- 21903662
TI  - The intersection of long-term care and end-of-life care.
AB  - High-quality end-of-life care is an important component of high-quality long-term
      care, yet many elderly individuals receiving long-term care services do not
      obtain good care as they approach death. This study provides a systematic review
      of articles that describe care received at the nexus of long-term care and end-of
      life care. The articles identified three primary types of barriers to high
      quality end-of-life care in long-term care settings: delivery system barriers
      intrinsic to long-term care settings, barriers related to features of coverage
      and reimbursement, and barriers resulting from the current regulatory approach
      for long-term care providers. The authors recommend areas for future research
      that would help to support progress on public policy that governs the provision
      of care at this important intersection.

PMID- 21903663
TI  - Covered today, sick tomorrow? Trends and correlates of children's health
      insurance instability.
AB  - Many children with health insurance will experience gaps in coverage over time,
      potentially reducing their access to and use of preventive health care services.
      This article uses the Survey of Income and Program Participation to examine how
      the stability of children's health insurance changed between 1990 and 2005 and to
      identify dynamic aspects of family life associated with transitions in coverage.
      Children's health insurance instability has increased since the early 1990s, due
      to greater movement between insured and uninsured states and between private and
      public insurance coverage. Changes in the employment and marital status of the
      family head are highly associated with an increased risk of a child losing and
      gaining public and private coverage, largely in hypothesized directions. The
      exception is that marital dissolution and job loss are associated with an
      increased probability of a child losing public insurance, despite there being no
      clear policy explanation for such a relationship.

PMID- 21903664
TI  - Impact of cannabis use on thalamic volume in people at familial high risk of
      schizophrenia.
AB  - BACKGROUND: No longitudinal study has yet examined the association between
      substance use and brain volume changes in a population at high risk of
      schizophrenia. AIMS: To examine the effects of cannabis on longitudinal thalamus
      and amygdala-hippocampal complex volumes within a population at high risk of
      schizophrenia. METHOD: Magnetic resonance imaging scans were obtained from
      individuals at high genetic risk of schizophrenia at the point of entry to the
      Edinburgh High-Risk Study (EHRS) and approximately 2 years later. Differential
      thalamic and amygdala-hippocampal complex volume change in high-risk individuals
      exposed (n = 25) and not exposed (n = 32) to cannabis in the intervening period
      was investigated using repeated-measures analysis of variance. RESULTS: Cannabis
      exposure was associated with bilateral thalamic volume loss. This effect was
      significant on the left (F = 4.47, P = 0.04) and highly significant on the right
      (F= 7.66, P= 0.008). These results remained significant when individuals using
      other illicit drugs were removed from the analysis. CONCLUSIONS: These are the
      first longitudinal data to demonstrate an association between thalamic volume
      loss and exposure to cannabis in currently unaffected people at familial high
      risk of developing schizophrenia. This observation may be important in
      understanding the link between cannabis exposure and the subsequent development
      of schizophrenia.

PMID- 21903665
TI  - Long-term sickness absence among patients with chronic fatigue syndrome.
AB  - Chronic fatigue syndrome is associated with high levels of occupational
      disability. Consecutive out-patients at a chronic fatigue syndrome treatment
      service were studied for associations between occupational status, symptom
      severity and cognitive and behavioural responses to symptoms. All patients had
      high symptom levels; however, those on long-term sickness absence had
      significantly more physical fatigue (beta = 0.098, P<0.05) and worse sleep (beta
      = 0.075, P<0.05). Patients with long-term sickness absence also demonstrated more
      embarrassment avoidance cognitions (beta = 0.086, P<0.05) and avoidance resting
      behavioural responses (beta = 0.078, P<0.05). Identifying and addressing
      avoidance behaviours and cognitions regarding embarrassment in interventions may
      enhance the chances of individuals returning to work.

PMID- 21903666
TI  - Relationship of orthostatic blood pressure to white matter hyperintensities and
      subcortical volumes in late-life depression.
AB  - BACKGROUND: Structural brain abnormalities are associated with late-life major
      depression, with numerous studies reporting increased white matter
      hyperintensities (WMH) and reduced cortical/subcortical grey matter volumes.
      There is strong evidence linking vascular disease to WMH, but limited evidence on
      its association with subcortical volumes. AIMS: To investigate the relationship
      of orthostatic blood pressure changes to WMH and subcortical grey matter volumes
      in late-life depression. METHOD: Thirty-eight people with depression and a
      similarly aged comparison group (n = 30) underwent fluid attenuated inversion
      recovery (FLAIR) and T(1)-weighted magnetic resonance imaging as well as
      systematic orthostatic blood pressure assessments. Volumetric estimates of WMH
      and subcortical grey matter were obtained for each participant and the
      relationship to blood pressure drop on active stand was examined. RESULTS: An
      association between orthostatic systolic blood pressure drop and WMH volumes in
      temporal and parietal regions was found in the depression group (age-corrected
      partial correlation r' = 0.31-0.35, P<0.05). Subcortical volumes were not related
      to blood pressure changes or WMH volumes in either group. CONCLUSIONS: We found
      evidence for an association between the degree of orthostatic systolic blood
      pressure drop and WMH volume in the depression group. Since blood pressure drops
      lead to WMH in animals our findings suggest systolic blood pressure drops may be
      a factor contributing to these lesions in late-life depression.

PMID- 21903667
TI  - Dysregulation of Semaphorin7A/beta1-integrin signaling leads to defective GnRH-1
      cell migration, abnormal gonadal development and altered fertility.
AB  - Reproduction in mammals is dependent on the function of specific neurons that
      secrete gonadotropin-releasing hormone-1 (GnRH-1). These neurons originate
      prenatally in the nasal placode and migrate into the forebrain along the
      olfactory-vomeronasal nerves. Alterations in this migratory process lead to
      defective GnRH-1 secretion, resulting in heterogeneous genetic disorders such as
      idiopathic hypogonadotropic hypogonadism (IHH), and other reproductive diseases
      characterized by the reduction or failure of sexual competence. Combining mouse
      genetics with in vitro models, we demonstrate that Semaphorin 7A (Sema7A) is
      essential for the development of the GnRH-1 neuronal system. Loss of Sema7A
      signaling alters the migration of GnRH-1 neurons, resulting in significantly
      reduced numbers of these neurons in the adult brain as well as in reduced gonadal
      size and subfertility. We also show that GnRH-1 cells differentially express the
      Sema7 receptors beta1-integrin and Plexin C1 as a function of their migratory
      stage, whereas the ligand is robustly expressed along developing
      olfactory/vomeronasal fibers. Disruption of Sema7A function in vitro inhibits
      beta1-integrin-mediated migration. Analysis of Plexin C1(-/-) mice did not reveal
      any difference in the migratory process of GnRH-1 neurons, indicating that Sema7A
      mainly signals through beta1-integrin to regulate GnRH-1 cell motility. In
      conclusion, we have identified Sema7A as a gene implicated in the normal
      development of the GnRH-1 system in mice and as a genetic marker for the
      elucidation of some forms of GnRH-1 deficiency in humans.

PMID- 21903669
TI  - Normal mammalian cells negatively regulate telomere length by telomere trimming.
AB  - In human cancer cells with telomeres that have been over-lengthened by exogenous
      telomerase activity, telomere shortening can occur by a process that generates
      circles of double-stranded telomeric DNA (t-circles). Here, we demonstrate that
      this telomeretrimming process occurs in cells of the male germline and in normal
      lymphocytes following mitogen-stimulated upregulation of telomerase activity.
      Mouse tissues also contain abundant t-circles, suggesting that telomere trimming
      also contributes to telomere length regulation in mice. In cancer cells and
      stimulated lymphocytes, the mechanism involves the XRCC3 homologous recombination
      (HR) protein and generates single-stranded C-rich telomeric DNA. This suggests
      that, in addition to the well-documented gradual telomere attrition that
      accompanies cellular replication, there is also a more rapid form of negative
      telomere length control in normal mammalian cells, which most likely involves HR
      mediated removal of telomere loops in the form of t-circles. We therefore propose
      that this telomere trimming mechanism is an additional factor in the balance
      between telomere lengthening and telomere shortening in normal human germline and
      somatic cells that may prevent excessive lengthening by processes such as
      telomerase activity.

PMID- 21903668
TI  - Behavioral alterations associated with targeted disruption of exons 2 and 3 of
      the Disc1 gene in the mouse.
AB  - Disrupted-In-Schizophrenia 1 (DISC1) is a promising candidate gene for
      susceptibility to psychiatric disorders, including schizophrenia. DISC1 appears
      to be involved in neurogenesis, neuronal migration, axon/dendrite formation and
      synapse formation; during these processes, DISC1 acts as a scaffold protein by
      interacting with various partners. However, the lack of Disc1 knockout mice and a
      well-characterized antibody to DISC1 has made it difficult to determine the exact
      role of DISC1 in vivo. In this study, we generated mice lacking exons 2 and 3 of
      the Disc1 gene and prepared specific antibodies to the N- and C-termini of DISC1.
      The Disc1 mutant mice are viable and fertile, and no gross phenotypes, such as
      disorganization of the brain's cytoarchitecture, were observed. Western blot
      analysis revealed that the DISC1-specific antibodies recognize a protein with an
      apparent molecular mass of ~100 kDa in brain extracts from wild-type mice but not
      in brain extracts from DISC1 mutant mice. Immunochemical studies demonstrated
      that DISC1 is mainly localized to the vicinity of the Golgi apparatus in
      hippocampal neurons and astrocytes. A deficiency of full-length Disc1 induced a
      threshold shift in the induction of long-term potentiation in the dentate gyrus.
      The Disc1 mutant mice displayed abnormal emotional behavior as assessed by the
      elevated plus-maze and cliff-avoidance tests, thereby suggesting that a
      deficiency of full-length DISC1 may result in lower anxiety and/or higher
      impulsivity. Based on these results, we suggest that full-length Disc1-deficient
      mice and DISC1-specific antibodies are powerful tools for dissecting the
      pathophysiological functions of DISC1.

PMID- 21903670
TI  - Dynamic localization of C. elegans TPR-GoLoco proteins mediates mitotic spindle
      orientation by extrinsic signaling.
AB  - Cell divisions are sometimes oriented by extrinsic signals, by mechanisms that
      are poorly understood. Proteins containing TPR and GoLoco-domains (C. elegans GPR
      1/2, Drosophila Pins, vertebrate LGN and AGS3) are candidates for mediating
      mitotic spindle orientation by extrinsic signals, but the mechanisms by which TPR
      GoLoco proteins may localize in response to extrinsic cues are not well defined.
      The C. elegans TPR-GoLoco protein pair GPR-1/2 is enriched at a site of contact
      between two cells - the endomesodermal precursor EMS and the germline precursor
      P(2) - and both cells align their divisions toward this shared cell-cell contact.
      To determine whether GPR-1/2 is enriched at this site within both cells, we
      generated mosaic embryos with GPR-1/2 bearing a different fluorescent tag in
      different cells. We were surprised to find that GPR-1/2 distribution is symmetric
      in EMS, where GPR-1/2 had been proposed to function as an asymmetric cue for
      spindle orientation. Instead, GPR-1/2 is asymmetrically distributed only in P(2).
      We demonstrate a role for normal GPR-1/2 localization in P(2) division
      orientation. We show that MES-1/Src signaling plays an instructive role in P(2)
      for asymmetric GPR-1/2 localization and normal spindle orientation. We ruled out
      a model in which signaling localizes GPR-1/2 by locally inhibiting LET-99, a GPR
      1/2 antagonist. Instead, asymmetric GPR-1/2 distribution is established by
      destabilization at one cell contact, diffusion, and trapping at another cell
      contact. Once the mitotic spindle of P(2) is oriented normally, microtubule
      dependent removal of GPR-1/2 prevented excess accumulation, in an apparent
      negative-feedback loop. These results highlight the role of dynamic TPR-GoLoco
      protein localization as a key mediator of mitotic spindle alignment in response
      to instructive, external cues.

PMID- 21903671
TI  - Rhou maintains the epithelial architecture and facilitates differentiation of the
      foregut endoderm.
AB  - Rhou encodes a Cdc42-related atypical Rho GTPase that influences actin
      organization in cultured cells. In mouse embryos at early-somite to early
      organogenesis stages, Rhou is expressed in the columnar endoderm epithelium
      lining the lateral and ventral wall of the anterior intestinal portal. During
      foregut development, Rhou is downregulated in regions where the epithelium
      acquires a multilayered morphology heralding the budding of organ primordia. In
      embryos generated from Rhou knockdown embryonic stem (ES) cells, the embryonic
      foregut displays an abnormally flattened shape. The epithelial architecture of
      the endoderm is disrupted, the cells are depleted of microvilli and the
      phalloidin-stained F-actin content of their sub-apical cortical domain is
      reduced. Rhou-deficient cells in ES cell-derived embryos and embryoid bodies are
      less efficient in endoderm differentiation. Impaired endoderm differentiation of
      Rhou-deficient ES cells is accompanied by reduced expression of c-Jun/AP-1 target
      genes, consistent with a role for Rhou in regulating JNK activity. Downregulation
      of Rhou in individual endoderm cells results in a reduced ability of these cells
      to occupy the apical territory of the epithelium. Our findings highlight
      epithelial morphogenesis as a required intermediate step in the differentiation
      of endoderm progenitors. In vivo, Rhou activity maintains the epithelial
      architecture of the endoderm progenitors, and its downregulation accompanies the
      transition of the columnar epithelium in the embryonic foregut to a multilayered
      cell sheet during organ formation.

PMID- 21903673
TI  - Control of final organ size by Mediator complex subunit 25 in Arabidopsis
      thaliana.
AB  - Control of organ size by cell proliferation and cell expansion is a fundamental
      developmental process, but the mechanisms that establish the final size of organs
      and whole organisms remain elusive in plants and animals. We have previously
      demonstrated that DA1, which encodes a predicted ubiquitin receptor, controls the
      final size of seeds and organs by restricting cell proliferation in Arabidopsis.
      Through a genetic screen for mutations that enhance the floral organ size of da1
      1, we have identified an enhancer of da1-1 (eod8-1). The eod8-1 mutation was
      identified, using a map-based cloning approach, in Mediator complex subunit 25
      (MED25; also known as PFT1), which is involved in the transcriptional regulation
      of gene expression. Loss-of-function mutants in MED25 form large organs, with
      larger and slightly increased numbers of cells as a result of an increased period
      of cell proliferation and cell expansion, whereas plants overexpressing MED25
      have small organs owing to decreases in both cell number and cell size. Our
      genetic and physiological data suggest that MED25 acts to limit cell and organ
      growth independently of MED25-mediated phytochrome signaling and the jasmonate
      pathway. Genetic analyses show that MED25 functions redundantly with DA1 to
      control organ growth by restricting cell proliferation. Collectively, our
      findings show that MED25 plays a crucial role in setting final organ size,
      suggesting that it constitutes an important point of regulation in plant organ
      size control within the transcriptional machinery.

PMID- 21903672
TI  - Maintaining embryonic stem cell pluripotency with Wnt signaling.
AB  - Wnt signaling pathways control lineage specification in vertebrate embryos and
      regulate pluripotency in embryonic stem (ES) cells, but how the balance between
      progenitor self-renewal and differentiation is achieved during axis specification
      and tissue patterning remains highly controversial. The context- and stage
      specific effects of the different Wnt pathways produce complex and sometimes
      opposite outcomes that help to generate embryonic cell diversity. Although the
      results of recent studies of the Wnt/beta-catenin pathway in ES cells appear to
      be surprising and controversial, they converge on the same conserved mechanism
      that leads to the inactivation of TCF3-mediated repression.

PMID- 21903674
TI  - Alpha sarcoglycan is required for FGF-dependent myogenic progenitor cell
      proliferation in vitro and in vivo.
AB  - Mice deficient in alpha-sarcoglycan (Sgca-null mice) develop progressive muscular
      dystrophy and serve as a model for human limb girdle muscular dystrophy type 2D.
      Sgca-null mice suffer a more severe myopathy than that of mdx mice, the model for
      Duchenne muscular dystrophy. This is the opposite of what is observed in humans
      and the reason for this is unknown. In an attempt to understand the cellular
      basis of this severe muscular dystrophy, we isolated clonal populations of
      myogenic progenitor cells (MPCs), the resident postnatal muscle progenitors of
      dystrophic and wild-type mice. MPCs from Sgca-null mice generated much smaller
      clones than MPCs from wild-type or mdx dystrophic mice. Impaired proliferation of
      Sgca-null myogenic precursors was confirmed by single fiber analysis and this
      difference correlated with Sgca expression during MPC proliferation. In the
      absence of dystrophin and associated proteins, which are only expressed after
      differentiation, SGCA complexes with and stabilizes FGFR1. Deficiency of Sgca
      leads to an absence of FGFR1 expression at the membrane and impaired MPC
      proliferation in response to bFGF. The low proliferation rate of Sgca-null MPCs
      was rescued by transduction with Sgca-expressing lentiviral vectors. When
      transplanted into dystrophic muscle, Sgca-null MPCs exhibited reduced
      engraftment. The reduced proliferative ability of Sgca-null MPCs explains, at
      least in part, the severity of this muscular dystrophy and also why wild-type
      donor progenitor cells engraft efficiently and consequently ameliorate disease.

PMID- 21903675
TI  - Renal collecting system growth and function depend upon embryonic gamma1 laminin
      expression.
AB  - In order to understand the functions of laminins in the renal collecting system,
      the Lamc1 gene was inactivated in the developing mouse ureteric bud (UB). Embryos
      bearing null alleles exhibited laminin deficiency prior to mesenchymal tubular
      induction and either failed to develop a UB with involution of the mesenchyme, or
      developed small kidneys with decreased proliferation and branching, delayed renal
      vesicle formation and postnatal emergence of a water transport deficit. Embryonic
      day 12.5 kidneys revealed an almost complete absence of basement membrane
      proteins and reduced levels of alpha6 integrin and FGF2. mRNA levels for
      fibroblast growth factor 2 (FGF2) and mediators of the GDNF/RET and WNT11
      signaling pathway were also decreased. Furthermore, collecting duct cells derived
      from laminin-deficient kidneys and grown in collagen gels were found to
      proliferate and branch slowly. The laminin-deficient cells exhibited decreased
      activation of growth factor- and integrin-dependent pathways, whereas heparin
      lyase-treated and beta1 integrin-null cells exhibited more selective decreases.
      Collectively, these data support a requirement of gamma1 laminins for assembly of
      the collecting duct system basement membrane, in which immobilized ligands act as
      solid-phase agonists to promote branching morphogenesis, growth and water
      transport functions.

PMID- 21903676
TI  - An inducible kras(V12) transgenic zebrafish model for liver tumorigenesis and
      chemical drug screening.
AB  - Because Ras signaling is frequently activated by major hepatocellular carcinoma
      etiological factors, a transgenic zebrafish constitutively expressing the
      kras(V12) oncogene in the liver was previously generated by our laboratory.
      Although this model depicted and uncovered the conservation between zebrafish and
      human liver tumorigenesis, the low tumor incidence and early mortality limit its
      use for further studies of tumor progression and inhibition. Here, we employed a
      mifepristone-inducible transgenic system to achieve inducible kras(V12)
      expression in the liver. The system consisted of two transgenic lines: the liver
      driver line had a liver-specific fabp10 promoter to produce the LexPR chimeric
      transactivator, and the Ras-effector line contained a LexA-binding site to
      control EGFP-kras(V12) expression. In double-transgenic zebrafish (driver
      effector) embryos and adults, we demonstrated mifepristone-inducible EGFP
      kras(V12) expression in the liver. Robust and homogeneous liver tumors developed
      in 100% of double-transgenic fish after 1 month of induction and the tumors
      progressed from hyperplasia by 1 week post-treatment (wpt) to carcinoma by 4 wpt.
      Strikingly, liver tumorigenesis was found to be 'addicted' to Ras signaling for
      tumor maintenance, because mifepristone withdrawal led to tumor regression via
      cell death in transgenic fish. We further demonstrated the potential use of the
      transparent EGFP-kras(V12) larvae in inhibitor treatments to suppress Ras-driven
      liver tumorigenesis by targeting its downstream effectors, including the Raf-MEK
      ERK and PI3K-AKT-mTOR pathways. Collectively, this mifepristone-inducible and
      reversible kras(V12) transgenic system offers a novel model for understanding
      hepatocarcinogenesis and a high-throughput screening platform for anti-cancer
      drugs.

PMID- 21903677
TI  - Evolution and functional diversification of fructose bisphosphate aldolase genes
      in photosynthetic marine diatoms.
AB  - Diatoms and other chlorophyll-c containing, or chromalveolate, algae are among
      the most productive and diverse phytoplankton in the ocean. Evolutionarily,
      chlorophyll-c algae are linked through common, although not necessarily
      monophyletic, acquisition of plastid endosymbionts of red as well as most likely
      green algal origin. There is also strong evidence for a relatively high level of
      lineage-specific bacterial gene acquisition within chromalveolates. Therefore,
      analyses of gene content and derivation in chromalveolate taxa have indicated
      particularly diverse origins of their overall gene repertoire. As a single group
      of functionally related enzymes spanning two distinct gene families, fructose 1,6
      bisphosphate aldolases (FBAs) illustrate the influence on core biochemical
      pathways of specific evolutionary associations among diatoms and other
      chromalveolates with various plastid-bearing and bacterial endosymbionts. Protein
      localization and activity, gene expression, and phylogenetic analyses indicate
      that the pennate diatom Phaeodactylum tricornutum contains five FBA genes with
      very little overall functional overlap. Three P. tricornutum FBAs, one class I
      and two class II, are plastid localized, and each appears to have a distinct
      evolutionary origin as well as function. Class I plastid FBA appears to have been
      acquired by chromalveolates from a red algal endosymbiont, whereas one copy of
      class II plastid FBA is likely to have originated from an ancient green algal
      endosymbiont. The other copy appears to be the result of a chromalveolate
      specific gene duplication. Plastid FBA I and chromalveolate-specific class II
      plastid FBA are localized in the pyrenoid region of the chloroplast where they
      are associated with beta-carbonic anhydrase, which is known to play a significant
      role in regulation of the diatom carbon concentrating mechanism. The two pyrenoid
      associated FBAs are distinguished by contrasting gene expression profiles under
      nutrient limiting compared with optimal CO2 fixation conditions, suggestive of a
      distinct specialized function for each. Cytosolically localized FBAs in P.
      tricornutum likely play a role in glycolysis and cytoskeleton function and seem
      to have originated from the stramenopile host cell and from diatom-specific
      bacterial gene transfer, respectively.

PMID- 21903678
TI  - Identification of an oxygenic reaction center psbADC operon in the cyanobacterium
      Gloeobacter violaceus PCC 7421.
AB  - Gloeobacter violaceus, the earliest diverging oxyphotobacterium (cyanobacterium)
      on the 16S ribosomal RNA tree, has five copies of the photosystem II psbA gene
      encoding the D1 reaction center protein subunit. These copies are widely
      distributed throughout the 4.6 Mbp genome with only one copy colocalizing with
      other PSII subunits, in marked contrast to all other psbA genes in all publicly
      available sequenced genomes. A clustering of two other psb genes around psbA3
      (glr2322) is unique to Gloeobacter. We provide experimental proof for the
      transcription of a psbA3DC operon, encoding three of the five reaction center
      core subunits (D1, D2, and CP43). This is the first example of a transcribed gene
      cluster containing the D1/D2 or D1/D2/CP43 subunits of PSII in an oxygenic
      phototroph (prokaryotic or eukaryotic). Implications for the evolution of
      oxygenic photosynthesis are discussed.

PMID- 21903679
TI  - An autosomal analysis gives no genetic evidence for complex speciation of humans
      and chimpanzees.
AB  - There have been conflicting arguments as to what happened in the human-chimpanzee
      speciation event. Patterson et al. (2006, Genetic evidence for complex speciation
      of humans and chimpanzees. Nature 441:1103-1108) proposed a hypothesis that the
      human-chimpanzee speciation event involved a complicated demographic process:
      that is, the ancestral lineages of humans and chimpanzees experienced temporal
      isolation followed by a hybridization event. This hypothesis stemmed from two
      major observations: a wide range of human-chimpanzee nucleotide divergence across
      the autosomal genome and very low divergence in the X chromosome. In contrast,
      Innan and Watanabe (2006, The effect of gene flow on the coalescent time in the
      human-chimpanzee ancestral population. Mol Biol Evol. 23:1040-1047) demonstrated
      that the null model of instantaneous speciation fits the genome-wide divergence
      data for the two species better than alternative models involving partial
      isolation and migration. To reconcile these two conflicting reports, we first
      reexamined the analysis of autosomal data by Patterson et al. (2006). By
      providing a theoretical framework for their analysis, we demonstrated that their
      observation is what is theoretically expected under the null model of
      instantaneous speciation with a large ancestral population. Our analysis
      indicated that the observed wide range of autosomal divergence is simply due to
      the coalescent process in the large ancestral population of the two species. To
      further verify this, we developed a maximum likelihood function to detect
      evidence of hybridization in genome-wide divergence data. Again, the null model
      with no hybridization best fits the data. We conclude that the simplest
      speciation model with instantaneous split adequately describes the human
      chimpanzee speciation event, and there is no strong reason to involve complicated
      factors in explaining the autosomal data.

PMID- 21903680
TI  - MUM-1 expression differentiates tumors in the PEComa family from clear cell
      sarcoma and melanoma.
AB  - PEComas are mesenchymal neoplasms composed of perivascular epithelioid cells
      (PEC) and include a spectrum of tumors. PEComas and malignant melanoma share
      common morphological, immunohistochemical, and ultrastructural features, such as
      epithelioid cell morphology and melanocytic immunophenotype. Melanocytic markers
      commonly expressed in PEC tumors include HMB-45, Melan-A/MART-1, tyrosinase,
      microphthalmia transcription factor (MITF), and occasionally, S100. Given this
      morphological and immunophenotypical overlap, the differential diagnosis between
      a PEComa and malignant melanoma can represent a challenge. Additional diagnostic
      difficulty is the differentiation of melanoma and PEComa from clear cell sarcoma
      that is indistinguishable from melanoma based on the immunohistochemical profile.
      Recent studies have shown that MUM-1, a known lymphocyte marker shows positive
      immunostaining in nevi and melanomas, its expression in PEComas and clear cell
      sarcoma, however, has not been previously addressed. In this study, the authors
      analyzed MUM-1 expression using immunohistochemistry in PEComas (n = 8), the
      PEComa family members, angiomyolipomas (n = 13), and clear cell sarcomas (n = 11)
      and compared the staining pattern with malignant melanomas (n = 25), both primary
      (n = 14) and metastatic (n = 11). It was found that 92.3% of primary melanomas
      and 81.3% of metastatic melanomas were MUM-1 positive. In contrast, MUM-1 was
      only weakly positive in only 25% of PEComas and negative in all angiomyolipomas.
      MUM-1 expression was noted in 72.7% of clear cell sarcomas. The study
      demonstrated differential MUM-1 expression between PEComas and other true
      melanocytic tumors and suggested that the addition of MUM-1 to the usual panel of
      melanocyte markers could be a helpful adjunctive study to aid in the differential
      diagnosis between these entities.

PMID- 21903681
TI  - Virtual electron microscopy: a simple implementation creating a new paradigm in
      ultrastructural examination.
AB  - Ultrastructural examination is a time-consuming and tiring process, requiring
      search for diagnostic features on a low-contrast screen in a dim environment.
      This article describes a method to circumvent these problems through the creation
      of a virtual ultrathin slide. This can be achieved by automated capturing of
      hundreds of images at high magnification and stitching them together into a
      digital image with a resolution of 4 nm/pixel. The pathologist can then navigate
      the virtual slide at his/her workstation computer. The image shows good contrast
      and resolution for diagnostic purposes, and most important, the pathologist can
      precisely note where the specific ultrastructural features are located. The setup
      required to implement virtual electron microscopy includes a transmission
      electron microscope equipped with motorized stage and automated digital image
      capture function, 2 free software components, self-developed software, and a
      desktop-grade computer. Besides use in daily diagnosis, virtual electron
      microscopy can open up many new applications such as undergraduate teaching,
      pathology resident training, external quality assurance program, and expert
      consultation.

PMID- 21903682
TI  - Renal cell carcinoma with extensive oncocytic features.
AB  - Oncocytic features are a hallmark of renal oncocytoma, but can be seen in other
      renal tumors such as clear cell renal cell carcinoma with granular cells and
      eosinophilic variant of chromophobe cell tumors. Up to 5% of renal neoplasms are
      ultimately diagnosed as unclassified renal cell carcinoma with oncocytic features
      accounting for a significant number of these tumors. Also a recent morphological
      variant of mucinous tubular and spindle cell carcinoma with oncocytic changes has
      been described, adding another challenge. Here we report an unusual case of
      unclassified renal cell carcinoma with extensive oncocytic changes and we discuss
      the differential diagnosis.

PMID- 21903683
TI  - Development and validation of the multidimensional state boredom scale.
AB  - This article describes the development and validation of the Multidimensional
      State Boredom Scale (MSBS)-the first and only full-scale measure of state
      boredom. It was developed based on a theoretically and empirically grounded
      definition of boredom. A five-factor structure of the scale (Disengagement, High
      Arousal, Low Arousal, Inattention, and Time Perception) was supported by
      exploratory factor analyses and confirmatory factor analyses of two independent
      samples. Furthermore, all subscales were significantly related to a single,
      second-order factor. The MSBS factor structure was shown to be invariant across
      gender. MSBS scores were significantly correlated with measures of trait boredom,
      depression, anxiety, anger, inattention, impulsivity, neuroticism, life
      satisfaction, and purpose in life. Finally, MSBS scores distinguished between
      participants who were experimentally manipulated into a state of boredom and
      those who were not, above and beyond measures of trait boredom, negative affect,
      and depression.

PMID- 21903684
TI  - Progression of reflux patterns in saphenous veins of women with chronic venous
      valvular insufficiency.
AB  - BACKGROUND: Venous ultrasonography identifies reflux patterns of the great and
      small saphenous veins (GSV, SSV), allowing evaluation of lower extremities for
      treatment planning and patient follow-up. OBJECTIVE: To determine progression of
      saphenous vein reflux patterns in women with primary venous valvular
      insufficiency. METHODS: Venous ultrasonography was performed in the extremities
      of 92 women, 43 +/- 12 (23-77) years old, CEAP (clinical, aetiological,
      anatomical and pathological elements) clinical classes C1-C2. Two examinations
      were performed 33 +/- 19 (8-89) months apart in patients without saphenous vein
      treatment. GSV and SSV reflux patterns were classified as segmental,
      multisegmental, distal, proximal, diffuse and normal. Prevalence was determined
      for each examination, separately for right and left extremities, and jointly.
      Prevalence was compared using chi2 statistics. RESULTS: Reflux prevalence was
      higher for the GSV, 89% (164/184) and 88% (n = 162), than for the SSV, 24% (n =
      45) and 30% (n = 56), respectively for first and second examinations (P < 0.001).
      Reflux pattern prevalence was not significantly different in the right and left
      extremities (1.0 > P > 0.14). Most prevalent patterns were (a) GSV segmental
      reflux initially, 41% (76/184), decreasing to 28% (52/184) (P = 0.009), and (b)
      GSV multisegmental reflux at the second examination, increasing from 26% (48/184)
      to 40% (73/184) (P = 0.006). Prevalence of other GSV or SSV reflux patterns did
      not change significantly (0.88 > P > 0.19). CONCLUSIONS: We documented early
      findings and venous reflux progression in a specific population of women with
      varicose veins, reticular veins and telangiectasias. GSV segmental reflux was
      most prevalent initially, progressing to GSV multisegmental reflux.

PMID- 21903685
TI  - Morphological and haemodynamic abnormalities in the jugular veins of patients
      with multiple sclerosis.
AB  - OBJECTIVES: Multiple areas of stenosis and different levels of obstruction of
      internal jugular and azygous veins (a condition known as cronic cerebrospinal
      venous insufficiency) recently emerged as an additional theory to the well-known
      autoimmune concept, explaining etiology of multiple sclerosis (MS). The aim of
      our study was to evaluate internal jugular vein (IJV) morphology and haemodynamic
      characteristics in patients with MS and compare it with well-matched healthy
      individuals and to evaluate the prevalence of venous flow abnormalities in both
      groups. METHODS: Sixty-four patients with clinically proven MS and 37 healthy
      individuals were included in our study. In all patients, IJV morphology and
      haemodynamic characteristics were evaluated by colour Doppler sonography as well
      as venous flow disorder. The patients were classified into four groups according
      to MS clinical form presentation. The prevalence of morphological and
      haemodynamic abnormalities in the IJV were assessed. RESULTS: The presence of
      stenosing lesion, mostly intraluminal defects like abnormal IJV valves, were
      observed in 28 patients (43%) in the MS group, and in 17 patients (45.9%) in the
      control group (P = NS). By adding haemodynamic Doppler information in the IJV
      venous outflow was significantly different in 42% of MS patients showing flow
      abnormalities (27/64), as compared with 8.1% of the controls (3/37), P < 0.001.
      CONCLUSION: In our group of patients, patients suffering from MS had
      significantly more IJV morphological changes and haemodynamic abnormalities when
      compared with healthy individuals not suffering from MS. These findings can be
      well demonstrated by non-invasive and cost-effective Doppler ultrasound.

PMID- 21903686
TI  - Complexity: a potential paradigm for a health promotion discipline.
AB  - Health promotion underpins a distancing from narrow, simplifying health
      approaches associated with the biomedical model. However, it has not yet
      succeeded in formally establishing its theoretical, epistemological and
      methodological foundations on a single paradigm. The complexity paradigm, which
      it has yet to broach head-on, might provide it with a disciplinary matrix in line
      with its implicit stances and basic values. This article seeks to establish
      complexity's relevance as a paradigm that can contribute to the development of a
      health promotion discipline. The relevance of complexity is justified primarily
      by its matching with several implicit epistemological and
      methodological/theoretical stances found in the cardinal concepts and principles
      of health promotion. The transcendence of ontological realism and determinism as
      well as receptiveness in respect of the reflexivity that complexity encompasses
      are congruent with the values of social justice, participation, empowerment and
      the concept of positive health that the field promotes. Moreover, from a
      methodological and theoretical standpoint, complexity assumes a holistic,
      contextual and transdisciplinary approach, toward which health promotion is
      tending through its emphasis on ecology and interdisciplinary action. In a quest
      to illustrate our position, developmental evaluation is presented as an example
      of practice stemming from a complexity paradigm that can be useful in the
      evaluation of health promotion initiatives. In short, we argue that it would be
      advantageous for health promotion to integrate this paradigm, which would provide
      it with a formal framework appropriate to its purposes and concerns. 

PMID- 21903687
TI  - A journey into school health promotion: district implementation of the health
      promoting schools approach.
AB  - The health-promoting schools approach has gained momentum in the last decade with
      many jurisdictions providing guidelines and frameworks for general
      implementation. Although general agreement exists as to the broad strokes needed
      for effectiveness, less apparent are local implementation designs and models. The
      Battle River Project was designed to explore one such local implementation
      strategy for a provincial (Alberta, Canada) health promoting schools program.
      Located in the Battle River School Division, the project featured a partnership
      between Ever Active Schools, the school division and the local health authority.
      Case study was used to come to a greater understanding of how the health
      promoting schools approach worked in this particular school authority and model.
      Three themes emerged: participation, coordination and, integration.

PMID- 21903688
TI  - How should GAVI build on its success?

PMID- 21903689
TI  - Changes in severity of 2009 pandemic A/H1N1 influenza in England: a Bayesian
      evidence synthesis.
AB  - OBJECTIVE: To assess the impact of the 2009 A/H1N1 influenza pandemic in England
      during the two waves of activity up to end of February 2010 by estimating the
      probabilities of cases leading to severe events and the proportion of the
      population infected. DESIGN: A Bayesian evidence synthesis of all available
      relevant surveillance data in England to estimate severity of the pandemic. DATA
      SOURCES: All available surveillance systems relevant to the pandemic 2009 A/H1N1
      influenza outbreak in England from June 2009 to February 2010. Pre-existing
      influenza surveillance systems, including estimated numbers of symptomatic cases
      based on consultations to the health service for influenza-like illness and cross
      sectional population serological surveys, as well as systems set up in response
      to the pandemic, including follow-up of laboratory confirmed cases up to end of
      June 2009 (FF100 and Fluzone databases), retrospective and prospective follow-up
      of confirmed hospitalised cases, and reported deaths associated with pandemic
      2009 A/H1N1 influenza. Main outcome measures Age specific and wave specific
      probabilities of infection and symptomatic infection resulting in
      hospitalisation, intensive care admission, and death, as well as infection attack
      rates (both symptomatic and total). The probabilities of intensive care admission
      and death given hospitalisation over time are also estimated to evaluate
      potential changes in severity across waves. RESULTS: In the summer wave of A/H1N1
      influenza, 0.54% (95% credible interval 0.33% to 0.82%) of the estimated 606,100
      (419,300 to 886,300) symptomatic cases were hospitalised, 0.05% (0.03% to 0.08%)
      entered intensive care, and 0.015% (0.010% to 0.022%) died. These correspond to
      3200 (2300 to 4700) hospital admissions, 310 (200 to 480) intensive care
      admissions, and 90 (80 to 110) deaths in the summer wave. In the second wave,
      0.55% (0.28% to 0.89%) of the 1,352,000 (829,900 to 2,806,000) estimated
      symptomatic cases were hospitalised, 0.10% (0.05% to 0.16%) were admitted to
      intensive care, and 0.025% (0.013% to 0.040%) died. These correspond to 7500
      (5900 to 9700) hospitalisations, 1340 (1030 to 1790) admissions to intensive
      care, and 240 (310 to 380) deaths. Just over a third (35% (26% to 45%)) of
      infections were estimated to be symptomatic. The estimated probabilities of
      infections resulting in severe events were therefore 0.19% (0.12% to 0.29%),
      0.02% (0.01% to 0.03%), and 0.005% (0.004% to 0.008%) in the summer wave for
      hospitalisation, intensive care admission, and death respectively. The
      corresponding second wave probabilities are 0.19% (0.10% to 0.32%), 0.03% (0.02%
      to 0.06%), and 0.009% (0.004% to 0.014%). An estimated 30% (20% to 43%) of
      hospitalisations were detected in surveillance systems in the summer, compared
      with 20% (15% to 25%) in the second wave. Across the two waves, a mid-estimate of
      11.2% (7.4% to 18.9%) of the population of England were infected, rising to 29.5%
      (16.9% to 64.1%) in 5-14 year olds. Sensitivity analyses to the evidence included
      suggest this infection attack rate could be as low as 5.9% (4.2% to 8.7%) or as
      high as 28.4% (26.0% to 30.8%). In terms of the probability that an infection
      leads to death in the second wave, these correspond, respectively, to a high
      estimate of 0.017% (0.011% to 0.024%) and a low estimate of 0.0027% (0.0024% to
      0.0031%). CONCLUSIONS: This study suggests a mild pandemic, characterised by case
      and infection severity ratios increasing between waves. Results suggest low
      ascertainment rates, highlighting the importance of systems enabling early robust
      estimation of severity, to inform optimal public health responses, particularly
      in light of the apparent resurgence of the 2009 A/H1N1 strain in the 2010-11
      influenza season.

PMID- 21903690
TI  - The Global Fund resumes grants to China.

PMID- 21903691
TI  - British Thoracic Society guidelines for the management of community acquired
      pneumonia in children: update 2011.
AB  - The British Thoracic Society first published management guidelines for community
      acquired pneumonia in children in 2002 and covered available evidence to early
      2000. These updated guidelines represent a review of new evidence since then and
      consensus clinical opinion where evidence was not found. This document
      incorporates material from the 2002 guidelines and supersedes the previous
      guideline document.

PMID- 21903692
TI  - Views and experiences of men who have sex with men on the ban on blood donation:
      a cross sectional survey with qualitative interviews.
AB  - OBJECTIVE: To explore compliance with the UK blood services' criterion that
      excludes men who have had penetrative sex with a man from donating blood, and to
      assess the possible effects of revising this policy. DESIGN: A random location,
      cross sectional survey followed by qualitative interviews. SETTING: Britain.
      PARTICIPANTS: 1028 of 32,373 men in the general population reporting any male
      sexual contact completed the survey. Additional questions were asked of a general
      population sample (n=3914). Thirty men who had had penetrative sex with a man
      participated in the qualitative interviews (19 who had complied with the blood
      services' exclusion criterion and 11 who had not complied). Main outcome measure
      Compliance with the blood services' lifetime exclusion criterion for men who have
      had penetrative sex with a man. RESULTS: 10.6% of men with experience of
      penetrative sex with a man reported having donated blood in Britain while
      ineligible under the exclusion criterion, and 2.5% had donated in the previous 12
      months. Ineligible donation was less common among men who had had penetrative sex
      with a man recently (in previous 12 months) than among men for whom this last
      occurred longer ago. Reasons for non-compliance with the exclusion included self
      categorisation as low risk, discounting the sexual experience that barred
      donation, belief in the infallibility of blood screening, concerns about
      confidentiality, and misunderstanding or perceived inequity of the rule. Although
      blood donation was rarely viewed as a "right," potential donors were seen as
      entitled to a considered assessment of risk. A one year deferral since last male
      penetrative sex was considered by study participants to be generally feasible,
      equitable, and acceptable. CONCLUSIONS: A minority of men who have sex with men
      who are ineligible to donate blood under the current donor exclusion in Britain
      have nevertheless done so in the past 12 months. Many of the reasons identified
      for non-compliance seem amenable to intervention. A clearly rationalised and
      communicated one year donor deferral is likely to be welcomed by most men who
      have sex with men.

PMID- 21903693
TI  - Target practice: choosing target conditions for test accuracy studies that are
      relevant to clinical practice.

PMID- 21903694
TI  - Royal College of General Practitioners launches guide to managing long term
      conditions.

PMID- 21903696
TI  - Vietnam is urged to close drug detention centres after widespread abuse is
      discovered.

PMID- 21903695
TI  - Time trends in mortality in patients with type 1 diabetes: nationwide population
      based cohort study.
AB  - OBJECTIVE: To examine short and long term time trends in mortality among patients
      with early onset (age 0-14 years) and late onset (15-29 years) type 1 diabetes
      and causes of deaths over time. DESIGN: Population based nationwide cohort study.
      SETTING: Finland. PARTICIPANTS: All Finnish patients diagnosed as having type 1
      diabetes below age 30 years between 1970 and 1999 (n = 17,306). MAIN OUTCOME
      MEASURES: Crude mortality, standardised mortality ratios, time trends, and
      cumulative mortality. RESULTS: A total of 1338 deaths occurred during 370,733
      person years of follow-up, giving an all cause mortality rate of 361/100,000
      person years. The standardised mortality ratio was 3.6 in the early onset cohort
      and 2.8 in the late onset cohort. Women had higher standardised mortality ratios
      than did men in both cohorts (5.5 v 3.0 in the early onset cohort; 3.6 v 2.6 in
      the late onset cohort). The standardised mortality ratio at 20 years' duration of
      diabetes in the early onset cohort decreased from 3.5 in the patients diagnosed
      in 1970-4 to 1.9 in those diagnosed in 1985-9. In contrast, the standardised
      mortality ratio in the late onset cohort increased from 1.4 in those diagnosed in
      1970-4 to 2.9 in those diagnosed in 1985-9. Mortality due to chronic
      complications of diabetes decreased with time in the early onset cohort but not
      in the late onset cohort. Mortality due to alcohol related and drug related
      causes increased in the late onset cohort and accounted for 39% of the deaths
      during the first 20 years of diabetes. Accordingly, mortality due to acute
      diabetic complications increased significantly in the late onset cohort.
      CONCLUSION: Survival of people with early onset type 1 diabetes has improved over
      time, whereas survival of people with late onset type 1 diabetes has deteriorated
      since the 1980s. Alcohol has become an important cause of death in patients with
      type 1 diabetes, and the proportion of deaths caused by acute complications of
      diabetes has increased in patients with late onset type 1 diabetes.

PMID- 21903697
TI  - Health bill passes to the Lords with majority of 65 votes.

PMID- 21903698
TI  - Attempt to strip abortion providers of counselling role is defeated.

PMID- 21903699
TI  - Former health minister questions why GPs did not sound alarm bells about Stafford
      hospital.

PMID- 21903700
TI  - Use of ultrasound biomicroscopy to evaluate induced ovarian follicular growth and
      ovulation in mice.
AB  - Recent advances in image technology, including significant gains in spatial
      resolution, have made realtime sequential ovarian evaluations possible in small
      rodents, allowing longitudinal (continued) studies of the ovarian cycle and
      reducing the required number of experimental animals. The aim of this study was
      to evaluate exogenous stimulated follicular growth in mice using high-resolution
      ultrasound technology. Female mice (n = 15) received a 5 IU intraperitoneal
      injection of equine chorionic gonadotropin (eCG) and 48 h later a 5 IU injection
      of human chorionic gonadotropin (hCG), and were allowed to mate thereafter. In
      experiment 1, animals (n = 7) were evaluated every 6 h, from 3 to 51 h after eCG
      injection, with an ultrasound biomicroscopy (UBM) equipped with a realtime 45 MHz
      microvisualization probe (RMV 707b). The ovaries were identified and follicular
      population quantified, and follicles were classified according to the diameter as
      small (<=449 um) or large (>=450 um). A significant change in the distribution of
      follicle population according to category was observed only 45 h after eCG
      injection (P < 0.05). In experiment 2, animals (n = 8) were evaluated every 2 h,
      from 2 h to 10 h after hCG treatment. The largest follicles reached a maximum
      size (596.7 +/- 106.0 um) 5.8 +/- 2.3 h after hCG injection. As expected, the
      population of large follicles decreased thereafter, indicating the progress of
      ovulations, but large follicles were still detected late after treatment (10.1 +/
      1.1 h). In conclusion, UBM can be used to evaluate follicle dynamics in
      superstimulated mice (C57BL/6 and BALB/c); significant changes in follicle
      distribution only occur at later stages after eCG stimulation; and hCG-induced
      ovulations may not occur synchronously in mice.

PMID- 21903702
TI  - Regulation of NMDA receptor subunits after acute ethanol treatment in rat brain.
AB  - AIMS: Tolerance to ethanol-induced inhibition of N-methyl-D-aspartate receptors
      (NMDARs) is thought to underlie the acute adaptive mechanisms against ethanol. To
      explore these compensatory upregulating mechanisms of NMDARs, we investigated the
      expression and phosphorylation of NMDAR subunits in vivo following an acute
      ethanol treatment. METHODS: Male Sprague-Dawley rats were given 4 g/kg ethanol,
      and the phospho-S896-NR1, NR2A and NR2B subunits of NMDAR were immunoblotted from
      the cerebral cortex and hippocampus. We also examined the mRNAs and ubiquitinated
      forms of the NR2A and NR2B subunits. RESULTS: Acute ethanol treatment increased
      phospho-S896-NR1 at 30 min in the cerebral cortex and hippocampus, and the
      increase was maintained until 2 h in the hippocampus. Ethanol increased total
      NR2A and NR2B expression at 30 min in the cortex and hippocampus, and the NR2A
      increase was maintained until 2 h in the hippocampus. The increased expression of
      the NR2A and NR2B subunits was not associated with statistically significant
      alterations in mRNA expression or protein ubiquitination. CONCLUSION: Acute
      ethanol treatment increased NR1 subunit phosphorylation and NR2A and NR2B subunit
      expression in the cerebral cortex and hippocampus of rats. These effects of
      ethanol on the NMDAR subunits may underlie the mechanisms that compensate for
      ethanol-induced inhibition of NMDARs. However, the regulation of NR2A and NR2B in
      this paradigm is not dependent on transcriptional changes.

PMID- 21903703
TI  - Ischaemic stroke following tranexamic acid in young patients carrying
      heterozygosity of MTHFR C677T.
AB  - The objective of this study is to report a new manifestation of acute stroke
      following antifibrinolytic agent administration in young women carrying
      heterozygosity for methylene-tetrahydrofolate reductase (MTHFR) C677T. The study
      included two young women who developed an acute ischaemic stroke following three
      days of tranexamic acid administration for bleeding gynaecological disorders.
      Case 1, a 44-year-old woman, presented left hemiplegia, mild dysarthria and
      anosognosia. Brain magnetic resonance imaging showed right ischaemic fronto
      temporal lesion due to subocclusion of the right middle cerebral artery. Case 2,
      a 49-year-old woman, developed aphasia and right hemiplegia. Neuroimaging showed
      left capsular and periventricular infarcts due to near occlusion of the left
      internal carotid artery. Thrombophilia screening, coagulation parameters,
      homocysteine testing, 12-lead electrocardiography, and transthoracic and
      transoesophageal echocardiography were unremarkable. Genetic assay showed that
      both patients carried heterozygosity for MTHFR C677T, in which cytosine (C) is
      replaced by thymidine (T) at base position 677. To our knowledge, this is the
      first report describing the association between genetic factors and the onset of
      stroke following antifibrinolytic drugs intake. These data suggest a synergic
      effect of plasminogen activator inhibitor and heterozygosity for MTHFR C677T on
      the pathogenetic mechanisms leading to ischaemic stroke in young people.

PMID- 21903701
TI  - Prospective memory in substance abusers at treatment entry: associations with
      education, neuropsychological functioning, and everyday memory lapses.
AB  - Individuals with substance use disorders (SUDs) commonly report lapses in
      prospective memory (PM) in their daily lives; however, our understanding of the
      profile and predictors of laboratory-based PM deficits in SUDs and their
      associations with everyday PM failures is still very preliminary. The current
      study examined these important questions using well-validated measures of self
      report and laboratory-based PM in a mixed cohort of 53 SUD individuals at
      treatment entry and 44 healthy adults. Consistent with prior research, the SUD
      group endorsed significantly more self-cued and environmentally based PM failures
      in their daily lives. Moreover, the SUD group demonstrated significantly lower
      time-based PM performance, driven largely by cue detection errors. The effect of
      SUDs on PM was particularly strong among participants with fewer years of
      education. Within the SUD cohort, time-based PM was correlated with clinical
      measures assessing executive functions, retrospective memory, and psychomotor
      speed. Importantly, time-based PM was uniquely associated with elevated PM
      failures in daily lives of the SUD participants, independent of current affective
      distress and other neurocognitive deficits. Findings suggest that individuals
      with SUD are vulnerable to deficits in PM, which may in turn increase their risk
      for poorer everyday functioning outcomes (e.g., treatment non-compliance).

PMID- 21903704
TI  - Hypothyroidism in preterm infants following normal screening.
AB  - Congenital hypothyroidism is screened for in the UK using blood spot thyroid
      stimulating hormone (TSH) screening at 5-8 d of age. Although standards are set
      by the UK Newborn Screening Programme Centre, there are variations in TSH cut
      offs used. The introduction of repeat screening of preterm babies at 36 weeks'
      gestational age in 2005 was controversial in its utility and timing. Two cases of
      preterm babies are presented, who had normal blood spot TSH values on the first
      test and who became screen positive when re-tested at term. The first with
      Trisomy 21 was born at 29 + 6 weeks with an initial blood spot TSH of 3.3 mU/L
      rising to 263 mU/L at term-corrected gestational age (plasma TSH 476.5 mU/L). The
      second was born at 24 + 6 weeks' gestational age and on day 7, the heel prick
      blood spot TSH was <2 mU/L, rising to 6.4 mU/L at 36 weeks corrected gestational
      age. After a barium enema, the plasma TSH increased to 66.6 mU/L with a free
      thyroxine of 7.6 pmol/L at day 101. Both cases were treated with thyroxine until
      death due to complications of prematurity. These cases illustrate the
      difficulties in screening for congenital hypothyroidism in preterm infants, due
      to the immaturity of the hypothalamo-pituitary-thyroid axis, and the effect of
      intercurrent illness and drugs on thyroid function. Despite a reassuring
      published review of 2200 preterm infants, these cases suggest that it may be
      unwise not to re-screen ex-preterm infants for congenital hypothyroidism at term.

PMID- 21903705
TI  - Pfetin as a prognostic biomarker for gastrointestinal stromal tumor: validation
      study in multiple clinical facilities.
AB  - OBJECTIVE: The aim of this study is to confirm the prognostic value of pfetin in
      gastrointestinal stromal tumor patients. We recently reported the utility of
      pfetin, a novel prognostic biomarker in gastrointestinal stromal tumor.
      Gastrointestinal stromal tumor spans a wide spectrum from cases with curable
      disease to those with fatal tumors due to metastasis and recurrence. There is no
      biomarker predicting metastasis and/or recurrence of gastrointestinal stromal
      tumor though imatinib mesylate can improve recurrence-free survival. METHODS:
      Pfetin expression was examined in 40 gastrointestinal stromal tumor patients from
      the Juntendo University Shizuoka Hospital using immunohistochemistry.
      Correlations between immunohistochemical findings and clinicopathologic
      parameters were examined. The pfetin expression results were integrated with the
      clinicopathologic data in a total of 299 cases including our 40 new
      gastrointestinal stromal tumor cases and 259 others with previously reported
      data. RESULTS: Immunohistochemical study demonstrated the disease-free survival
      rate to be 93.75% for pfetin-positive and 25.0% for pfetin-negative patients
      among the 40 cases from the Juntendo University Shizuoka Hospital (P= 0.0006).
      When all 299 cases were included, the disease-free survival rate was 92.44% for
      pfetin-positive and 60.81% for pfetin-negative patients (P< 0.0001). Both uni-
      and multivariate analyses revealed that, among the clinicopathologic parameters
      examined, only pfetin expression was an independent prognostic factor (P< 0.05).
      CONCLUSIONS: These results confirm the possible clinical utility of pfetin as a
      prognostic biomarker for gastrointestinal stromal tumor. Pfetin appears to be a
      novel clinically applicable prognostic factor, which may be useful for deciding
      whether to administer imatinib mesylate or not.

PMID- 21903706
TI  - The incidence and predictor of lymph node metastasis for patients with T1mi
      breast cancer who underwent axillary dissection and breast irradiation: an
      institutional analysis.
AB  - OBJECTIVE: This study was designed to evaluate the rate and the predictors of
      axillary lymph node metastasis in patients with T1mi breast cancer. METHODS: We
      analyzed 62 cases of ductal carcinoma in situ with microinvasion, and the
      pathology records and treatment charts were retrospectively reviewed for
      information on the patient and tumor characteristics. All the included patients
      underwent breast conserving surgery and 48 patients underwent axillary lymph node
      dissection. RESULTS: The incidence of axillary involvement was 8.3%. Comedo
      ductal carcinoma in situ (P = 0.031), histologic grade 3 (P = 0.025), the
      presence of necrosis (P = 0.007) and Van Nuys group 3 (P = 0.025) were
      significant predictors of axillary involvement on the statistical analysis.
      Axillary dissection was significantly associated with the occurrence of arm
      lymphedema (P = 0.030). CONCLUSIONS: A significant rate of axillary metastases
      occurred in the patients with T1mi breast carcinoma in this study. The comedo
      subtype of ductal carcinoma in situ, a high histologic grade, the presence of
      necrosis and the Van Nuys group 3 were significant predictors of axillary lymph
      node metastasis in patients with T1mi breast cancer. Thus, the patients with T1mi
      breast disease are indicated to a careful evaluation of axillary lymph node
      metastasis, if they have the earlier-mentioned unfavorable factors.

PMID- 21903707
TI  - Combination of gemcitabine and paclitaxel is a favorable option for patients with
      advanced or metastatic urothelial carcinoma previously treated with cisplatin
      based chemotherapy.
AB  - OBJECTIVE: To evaluate the efficacy and toxicity of a gemcitabine and paclitaxel
      regimen for patients with advanced urothelial carcinoma who had previously been
      treated with methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy,
      and to determine the prognostic factors for survival in second-line chemotherapy.
      METHODS: From June 2005 to April 2010, 24 eligible patients who had previously
      been treated with methotrexate, vinblastine, doxorubicin and cisplatin
      chemotherapy were enrolled in this study. Patients received paclitaxel 200
      mg/m(2) on Day 1 and gemcitabine 1000 mg/m(2) on Days 1, 8 and 15. The
      gemcitabine and paclitaxel regimen was repeated every 3 weeks. Patients were
      evaluated every two cycles by imaging study. RESULTS: Ten of 24 patients (42%)
      had major response to the gemcitabine and paclitaxel regimen, including 2
      patients (8%) who had complete response. Median survival time and median
      progression-free survival were 12.4 and 6.1 months, respectively. Good
      performance status and major response to first-line methotrexate, vinblastine,
      doxorubicin and cisplatin treatment were significant predictors of overall
      survival and progression-free survival. Grade 3 or 4 neutropenia occurred in 16
      patients (67%), but there were no severe infections. There were no treatment
      related deaths. CONCLUSIONS: Gemcitabine and paclitaxel chemotherapy had
      favorable benefit and safety profiles, and the regimen is recommended as a
      potential second-line chemotherapy for advanced or metastatic urothelial
      carcinoma previously treated with methotrexate, vinblastine, doxorubicin and
      cisplatin chemotherapy.

PMID- 21903708
TI  - Provision of menopause information must improve.

PMID- 21903709
TI  - IMS updates its recommendations on HRT.

PMID- 21903710
TI  - Effect of yoga on menopausal symptoms.
AB  - OBJECTIVES: To observe the effect of yoga on menopausal symptoms using a
      prospective, randomized, controlled and interventional study. Main outcome
      measures Total Menopause Rating Scale (MRS) score and three subscale scores
      (somatovegetative, psychological and urogenital) were measured on day 1 and day
      90 in the study group which performed yoga (asana, pranayam and meditation) under
      supervision for three months, and were compared with the control group that did
      not perform yoga. MRS has been designed to measure health-related quality of life
      of ageing women. It consists of 11 symptoms and three subscales. RESULTS: It was
      observed that on day 1 the scores in both the groups were comparable. On day 90,
      the scores in the yoga group showed a reduction in score on all the subscales,
      which was statistically significant. No significant difference was noted in the
      control group. CONCLUSION: Yoga is effective in reducing menopausal symptoms and
      should be considered as alternative therapy for the management of menopausal
      symptoms.

PMID- 21903711
TI  - Stopping hormone replacement therapy: were women ill advised?
AB  - OBJECTIVE: To survey women who stopped hormone replacement therapy (HRT) after
      2002, including those who later restarted. STUDY DESIGN: A questionnaire on the
      UK-based menopause website www.menopausematters.co.uk evaluating how women are
      influenced by HRT advice. Main outcome measures Answers to questions regarding
      stopping/restarting HRT in response to the advice in the early 2000s and advice
      given today. RESULTS: A total of 1100 responses were obtained. Of those who made
      the decision to stop HRT themselves, 56.4% (n = 425/754) said that they were
      influenced by the media. In those who would potentially most benefit from HRT,
      72.8% (n = 220/302) stopped without medical advice. Overall, women aged under 50
      years were significantly more likely to stop HRT themselves than women over 50 (P
      < 0.001). In women in whom symptoms returned, 37.5% (n = 362/966) said these
      affected their ability to work, 45.1% (n = 436) had problems with decision
      making, 53.6% (n = 518) admitted to relationships being negatively affected and
      29.2% (n = 286) said that symptoms affected their social relationships. Overall
      46.5% of women (n = 485/1044) would not have stopped HRT given the current
      understanding of risk. Compared with women over 50, significantly more women
      under the age of 50 said that they would not have previously stopped their HRT
      based on their current understanding of risk (P < 0.001). CONCLUSIONS: The
      negative impact of published research and its reporting from the early 2000s are
      being mitigated by current press coverage. Media reports appear to influence the
      younger woman more than the older woman. Health professionals and media must
      learn the lessons from the past.

PMID- 21903712
TI  - Global study of women's experiences of premenstrual symptoms and their effects on
      daily life.
AB  - OBJECTIVES: To determine cross-cultural and other effects on women's experiences
      of premenstrual symptoms and their impact on activities of daily life (ADL).
      STUDY DESIGN: Cross-sectional survey. Sample A total of 7226 women aged 15-49
      recruited by random sampling with approximately 400 each from France, Germany,
      Hungary, Italy, Spain, UK, Brazil, Mexico, Hong Kong, Pakistan and Thailand.
      Approximately 1000 women in Japan and Korea and 500 Australian women were found
      using Internet panels. MAIN OUTCOME MEASURES: Questionnaire of 23 premenstrual
      symptoms, sociodemographic and lifestyle variables, ADL and women's knowledge of
      premenstrual terms. RESULTS: The most prevalent symptoms were abdominal bloating,
      cramps or abdominal pain, irritability, mastalgia and joint/muscle/back pains.
      Severity of symptoms was directly proportional to duration (number of affected
      cycles) (R = 0.78). A linear model found that symptom prevalence (duration *
      severity) was associated with age (linear and quadratic effects), parity, current
      smoking and country. Premenstrual physical and mental symptom domains had similar
      negative effects on ADL. Impact on ADL was affected by education and exercise
      participation. Women's knowledge of the terms premenstrual syndrome (PMS) and
      premenstrual dysphoric disorder (PMDD) varied by symptom intensity, age,
      education and country. CONCLUSIONS: Four of the five most prevalent premenstrual
      symptoms were physical. There was a great deal of similarities of women's
      experiences of these symptoms across countries and regions. Women's knowledge of
      PMS terms is highly dependent on the country in which they live.

PMID- 21903713
TI  - Global epidemiological study of variation of premenstrual symptoms with age and
      sociodemographic factors.
AB  - OBJECTIVES: To determine patterns of premenstrual symptom experiences across the
      reproductive age range, and the effects of other factors on premenstrual
      symptoms. STUDY DESIGN: Global cross-sectional survey. Sample A total of 7226
      women aged 15-49 recruited by random sampling with approximately 400 each from
      France, Germany, Hungary, Italy, Spain, UK, Brazil, Mexico, Hong Kong, Pakistan
      and Thailand. Approximately 1000 women in Japan and Korea and 500 Australian
      women were found using Internet panels. MAIN OUTCOME MEASURES: Questionnaire of
      23 premenstrual symptoms, sociodemographic and lifestyle variables. RESULTS: Four
      different patterns of premenstrual symptoms were found with ageing: symptoms
      showing no change with age, symptoms decreasing with age, symptoms reaching a
      maximum just before or around age 35, and symptoms reaching a maximum around age
      40-44. Smoking was associated with an increase in most of the premenstrual
      symptoms. Increasing parity was associated with a decrease in some of the
      symptoms. CONCLUSIONS: These results suggest that the premenstrual symptoms most
      associated with the years of regular ovulatory cycles are skin disorders, lack of
      energy, appetite problems, joint/muscle/back pain, anger, abdominal bloating,
      depressed mood and irritability. Other symptoms which peaked later (swelling of
      extremities, breast tenderness/pain, weight gain) may reflect exacerbation by
      hormonal changes of the late reproductive/early menopausal transition. Smokers
      report more problematic premenstrual symptoms.

PMID- 21903714
TI  - Vitamin D and the postmenopausal population.
AB  - Vitamin D, a hormone critical to the body's maintenance of serum calcium and
      phosphorus concentrations, is currently the subject of much scientific interest.
      Low levels of vitamin D have been observed in many populations and
      epidemiological studies have suggested a link between this biochemical state and
      a range of diseases, such as cancer, diabetes and multiple sclerosis. While the
      consequence of vitamin D deficiency is well documented for bone (rickets and
      osteomalacia), with mixed findings relating to falls and fractures, a causal link
      between vitamin D deficiency and these wider health outcomes has not been
      established. If these relationships were found to be causal, the morbidity and
      mortality resulting from low levels of vitamin D could be substantial; the
      current evidence base, however, most robustly supports the assessment of serum
      25(OH)-vitamin D in the context of specific symptoms, low bone mineral density or
      biochemical abnormalities, rather than as an entity to treat in its own right or
      as the basis for a population-wide screening programme.

PMID- 21903715
TI  - Practice observed.

PMID- 21903718
TI  - Using participatory methods to examine policy and women prisoners' health.
AB  - This article describes how community-based participatory research (CBPR) led to
      the discovery of the unintended consequences of jail and prison copayment policy
      on women prisoners' health. The article addresses (a) a working definition of
      participatory research; (b) the importance of research with women prisoners; (c)
      the origins and development of our work and its grounding in CBPR; (d) issues
      related to research with prisoners; and (e) recommendations for using
      participatory methods to bring women prisoners into the discourse about the
      practices and policies that impact their lives. These methods have the potential
      to minimize the invisibility of prisoners and their health disparities.

PMID- 21903719
TI  - No "race to the bottom" on health care coverage.

PMID- 21903720
TI  - Perinatal exposure to bisphenol a increases adult mammary gland progesterone
      response and cell number.
AB  - Bisphenol A [BPA, 2,2,-bis (hydroxyphenyl) propane] is one of the highest-volume
      chemicals produced worldwide. It is detected in body fluids of more than 90% of
      the human population. Originally synthesized as an estrogenic compound, it is
      currently utilized to manufacture food and beverage containers resulting in
      uptake with food and drinks. There is concern that exposure to low doses of BPA,
      defined as less than or equal to 5 mg/kg body weight /d, may have developmental
      effects on various hormone-responsive organs including the mammary gland. Here,
      we asked whether perinatal exposure to a range of low doses of BPA is sufficient
      to alter mammary gland hormone response later on in life, with a possible impact
      on breast cancer risk. To mimic human exposure, we added BPA to the drinking
      water of C57/Bl6 breeding pairs. Analysis of the mammary glands of their
      daughters at puberty showed that estrogen-dependent transcriptional events were
      perturbed and the number of terminal end buds, estrogen-induced proliferative
      structures, was altered in a dose-dependent fashion. Importantly, adult females
      showed an increase in mammary epithelial cell numbers comparable to that seen in
      females exposed to diethylbestrol, a compound exposure to which was previously
      linked to increased breast cancer risk. Molecularly, the mRNAs encoding Wnt-4 and
      receptor activator of nuclear factor kappaB ligand, two key mediators of hormone
      function implicated in control of mammary stem cell proliferation and
      carcinogenesis, showed increased induction by progesterone in the mammary tissue
      of exposed mice. Thus, perinatal exposure to environmentally relevant doses of
      BPA alters long-term hormone response that may increase the propensity to develop
      breast cancer.

PMID- 21903721
TI  - Regulation of thyroid oxidative state by thioredoxin reductase has a crucial role
      in thyroid responses to iodide excess.
AB  - The phenomenon that supraphysiological doses of iodide (I(-)) temporarily inhibit
      thyroid hormone synthesis is known as thyroid iodide autoregulation. Recovery of
      thyroid function has been attributed to sodium-iodide symporter (NIS) inhibition,
      but the diversity of available data makes it difficult to reach definitive
      conclusions. Iodide excess induces reactive oxygen species production and cell
      toxicity. However, the roles of the oxidative state of the cell and antioxidant
      selenoproteins in I(-) autoregulation have never been explored. Here we analyze
      the effects of high I(-) doses in rat thyroids and in PCCl3 cells in the period
      comprising I(-) autoregulation (i.e. 0-72 h after I(-) administration), focusing
      on NIS expression, redox state, and the expression and activity of
      selenoproteins. Our results show that NIS mRNA inhibition by I(-) does not occur
      at the transcriptional level, because neither NIS promoter activity nor Pax8
      expression or its binding to DNA was modulated. Because I(-) uptake was inhibited
      much earlier than NIS protein, and no effect was observed on its subcellular
      localization, we suggest that I(-) is inhibiting NIS in the plasma membrane. The
      increased reactive oxygen species production leads to an increase in thioredoxin
      reductase mRNA levels and enzyme activity, which reduces the oxidative stress.
      Inhibition of thioredoxin reductase at either gene expression or activity levels
      prevented NIS recovery, thus illustrating a new role played by this selenoprotein
      in the regulation of cell homeostasis and consequently in I(-) autoregulation.

PMID- 21903724
TI  - Systems approaches to modelling pathways and networks.
AB  - It has become commonly accepted that systems approaches to biology are of
      outstanding importance to gain understanding from the vast amount of data which
      is presently being generated by advancing high-throughput technologies. The
      diversity of methods to model pathways and networks has significantly expanded
      over the past two decades. Modern and traditional approaches are equally
      important and recent activities aim at integrating the advantages of both. While
      traditional methods, based on differential equations, are useful to study the
      dynamics of small systems, modern constraint-based models can be applied to
      genome-scale systems, but are not able to capture dynamic features. Integrating
      different approaches is important to develop consistent theoretical descriptions
      encompassing various scales of biological information. The rapid progress of the
      field of theoretical systems biology, however, demonstrates how our fundamental
      theoretical understanding of biology is gaining momentum. The scientific
      community has apparently accepted the challenge to truly understand the
      principles of life.

PMID- 21903723
TI  - An integrative method for identifying the over-annotated protein-coding genes in
      microbial genomes.
AB  - The falsely annotated protein-coding genes have been deemed one of the major
      causes accounting for the annotating errors in public databases. Although many
      filtering approaches have been designed for the over-annotated protein-coding
      genes, some are questionable due to the resultant increase in false negative.
      Furthermore, there is no webserver or software specifically devised for the
      problem of over-annotation. In this study, we propose an integrative algorithm
      for detecting the over-annotated protein-coding genes in microorganisms. Overall,
      an average accuracy of 99.94% is achieved over 61 microbial genomes. The
      extremely high accuracy indicates that the presented algorithm is efficient to
      differentiate the protein-coding genes from the non-coding open reading frames.
      Abundant analyses show that the predicting results are reliable and the
      integrative algorithm is robust and convenient. Our analysis also indicates that
      the over-annotated protein-coding genes can cause the false positive of
      horizontal gene transfers detection. The webserver of the proposed algorithm can
      be freely accessible from www.cbi.seu.edu.cn/RPGM.

PMID- 21903722
TI  - Down-regulation of the histone methyltransferase EZH2 contributes to the
      epigenetic programming of decidualizing human endometrial stromal cells.
AB  - Differentiation of human endometrial stromal cells (HESC) into decidual cells
      represents a highly coordinated process essential for embryo implantation. We
      show that decidualizing HESC down-regulate the histone methyltransferase enhancer
      of Zeste homolog 2 (EZH2), resulting in declining levels of trimethylation of
      histone 3 on lysine 27 (H3K27me3) at the proximal promoters of key decidual
      marker genes PRL and IGFBP1. Loss of H3K27me3 was associated with a reciprocal
      enrichment in acetylation of the same lysine residue, indicating active
      remodeling from repressive to transcriptionally permissive chromatin. Chromatin
      immunoprecipitation coupled with DNA microarray analysis demonstrated that
      decidualization triggers genome-wide changes in H3K27me3 distribution that only
      partly overlap those observed upon EZH2 knockdown in undifferentiated HESC. Gene
      ontology revealed that gain of the repressive H3K27me3 mark in response to
      decidualization and upon EZH2 knockdown in undifferentiated cells was enriched at
      the promoter regions of genes involved in transcriptional regulation and
      growth/cell proliferation, respectively. However, loss of the H3K27me3 mark
      (indicating increased chromatin accessibility) in decidualizing cells and upon
      EZH2 knockdown occurred at selective loci enriched for genes functionally
      implicated in responses to stimulus. In agreement, EZH2 knockdown in
      undifferentiated HESC was sufficient to augment the induction of decidual marker
      genes in response to cyclic AMP and progesterone signaling. Thus, loss of EZH2
      dependent methyltransferase activity in the endometrium is integral to the
      process of chromatin remodeling that enables the transition from a proliferative
      to a decidual phenotype in response to differentiation cues.

PMID- 21903725
TI  - Catheter-based left atrial appendage occlusion procedure: role of
      echocardiography.
AB  - Atrial fibrillation is a common, clinically significant arrhythmic disorder that
      results in increased risk of morbidity and mortality in affected patients. Atrial
      fibrillation is more prevalent among men compared with women and the risk for
      developing atrial fibrillation increases with advancing age. Ischaemic stroke is
      the most common clinical manifestation of embolic events from atrial
      fibrillation. While anticoagulation treatment is the preferred treatment,
      unfortunately, many patients have contraindications for anticoagulation treatment
      making this option unavailable to them. Previous data have shown that most
      thrombi that form in association with non-valvular atrial fibrillation occur in
      the left atrial appendage (LAA). It has been suggested that isolating the LAA
      from the body of the left atrium might reduce the risk of embolic events and that
      LAA obliteration may be a treatment option for patients with atrial fibrillation
      who are not candidates for anticoagulation treatment. Several procedures have
      been developed for isolation of the LAA, including surgical procedures as well as
      catheter-based ones. In this paper, we will review the currently available
      techniques, emphasizing the catheter-based ones. We will examine the increasing
      role of real-time three-dimensional transoesophageal echocardiography for
      appropriate screening and patient selection for these procedures, intra
      procedural guidance, and follow-up care.

PMID- 21903726
TI  - Significant clinical, neuropathological and behavioural recovery from acute
      spinal cord trauma by transplantation of a well-defined somatic stem cell from
      human umbilical cord blood.
AB  - Stem cell therapy is a potential treatment for spinal cord injury and different
      stem cell types have been grafted into animal models and humans suffering from
      spinal trauma. Due to inconsistent results, it is still an important and
      clinically relevant question which stem cell type will prove to be
      therapeutically effective. Thus far, stem cells of human sources grafted into
      spinal cord mostly included barely defined heterogeneous mesenchymal stem cell
      populations derived from bone marrow or umbilical cord blood. Here, we have
      transplanted a well-defined unrestricted somatic stem cell isolated from human
      umbilical cord blood into an acute traumatic spinal cord injury of adult immune
      suppressed rat. Grafting of unrestricted somatic stem cells into the vicinity of
      a dorsal hemisection injury at thoracic level eight resulted in hepatocyte growth
      factor-directed migration and accumulation within the lesion area, reduction in
      lesion size and augmented tissue sparing, enhanced axon regrowth and significant
      functional locomotor improvement as revealed by three behavioural tasks (open
      field Basso-Beattie-Bresnahan locomotor score, horizontal ladder walking test and
      CatWalk gait analysis). To accomplish the beneficial effects, neither neural
      differentiation nor long-lasting persistence of the grafted human stem cells
      appears to be required. The secretion of neurite outgrowth-promoting factors in
      vitro further suggests a paracrine function of unrestricted somatic stem cells in
      spinal cord injury. Given the highly supportive functional characteristics in
      spinal cord injury, production in virtually unlimited quantities at GMP grade and
      lack of ethical concerns, unrestricted somatic stem cells appear to be a highly
      suitable human stem cell source for clinical application in central nervous
      system injuries.

PMID- 21903727
TI  - Data mining neocortical high-frequency oscillations in epilepsy and controls.
AB  - Transient high-frequency (100-500 Hz) oscillations of the local field potential
      have been studied extensively in human mesial temporal lobe. Previous studies
      report that both ripple (100-250 Hz) and fast ripple (250-500 Hz) oscillations
      are increased in the seizure-onset zone of patients with mesial temporal lobe
      epilepsy. Comparatively little is known, however, about their spatial
      distribution with respect to seizure-onset zone in neocortical epilepsy, or their
      prevalence in normal brain. We present a quantitative analysis of high-frequency
      oscillations and their rates of occurrence in a group of nine patients with
      neocortical epilepsy and two control patients with no history of seizures.
      Oscillations were automatically detected and classified using an unsupervised
      approach in a data set of unprecedented volume in epilepsy research, over 12
      terabytes of continuous long-term micro- and macro-electrode intracranial
      recordings, without human preprocessing, enabling selection-bias-free estimates
      of oscillation rates. There are three main results: (i) a cluster of ripple
      frequency oscillations with median spectral centroid = 137 Hz is increased in the
      seizure-onset zone more frequently than a cluster of fast ripple frequency
      oscillations (median spectral centroid = 305 Hz); (ii) we found no difference in
      the rates of high frequency oscillations in control neocortex and the non-seizure
      onset zone neocortex of patients with epilepsy, despite the possibility of
      different underlying mechanisms of generation; and (iii) while previous studies
      have demonstrated that oscillations recorded by parenchyma-penetrating micro
      electrodes have higher peak 100-500 Hz frequencies than penetrating macro
      electrodes, this was not found for the epipial electrodes used here to record
      from the neocortical surface. We conclude that the relative rate of ripple
      frequency oscillations is a potential biomarker for epileptic neocortex, but that
      larger prospective studies correlating high-frequency oscillations rates with
      seizure-onset zone, resected tissue and surgical outcome are required to
      determine the true predictive value.

PMID- 21903728
TI  - Neurofibrillary tangle pathology and Braak staging in chronic epilepsy in
      relation to traumatic brain injury and hippocampal sclerosis: a post-mortem
      study.
AB  - The long-term pathological effects of chronic epilepsy on normal brain ageing are
      unknown. Previous clinical and epidemiological studies show progressive cognitive
      decline in subsets of patients and an increased prevalence of Alzheimer's disease
      in epilepsy. In a post-mortem series of 138 patients with long-term, mainly drug
      resistant epilepsy, we carried out Braak staging for Alzheimer's disease
      neurofibrillary pathology using tau protein immunohistochemistry. The stages were
      compared with clinicopathological factors, including seizure history and presence
      of old traumatic brain injury. Overall, 31% of cases were Braak Stage 0, 36%
      Stage I/II, 31% Stage III/IV and 2% Stage V/VI. The mean age at death was 56.5
      years and correlated with Braak stage (P < 0.001). Analysis of Braak stages
      within age groups showed a significant increase in mid-Braak stages (III/IV), in
      middle age (40-65 years) compared with data from an ageing non-epilepsy series (P
      < 0.01). There was no clear relationship between seizure type (generalized or
      complex partial), seizure frequency, age of onset and duration of epilepsy with
      Braak stage although higher Braak stages were noted with focal more than with
      generalized epilepsy syndromes (P < 0.01). In 30% of patients, there was
      pathological evidence of traumatic brain injury that was significantly associated
      with higher Braak stages (P < 0.001). Cerebrovascular disease present in 40.3%
      and cortical malformations in 11.3% were not significantly associated with Braak
      stage. Astrocytic-tau protein correlated with the presence of both traumatic
      brain injury (P < 0.01) and high Braak stage (P < 0.001). Hippocampal sclerosis,
      identified in 40% (bilateral in 48%), was not associated with higher Braak
      stages, but asymmetrical patterns of tau protein accumulation within the
      sclerotic hippocampus were noted. In over half of patients with cognitive
      decline, the Braak stage was low indicating causes other than Alzheimer's disease
      pathology. In summary, there is evidence of accelerated brain ageing in severe
      chronic epilepsy although progression to high Braak stages was infrequent.
      Traumatic brain injury, but not seizures, was associated with tau protein
      accumulation in this series. It is likely that Alzheimer's disease pathology is
      not the sole explanation for cognitive decline associated with epilepsy.

PMID- 21903729
TI  - Hughlings Jackson's neurological ideas.
AB  - Hughlings Jackson's neurological ideas are scientifically valid and practically
      useful. He began by emphasizing the focal lesion as the key to analysing
      patients' symptoms. He proclaimed that 'Epilepsy is the name for occasional,
      sudden, excessive, rapid, and local discharge of grey matter.' He eliminated any
      need for a direct appeal to metaphysical agents by asserting that the nervous
      system is an exclusively sensorimotor machine constrained by the newly discovered
      conservation laws. In constructing his neurophysiology he accepted the
      phrenological assumption that the nervous system is composed of a number of
      physiologically discrete organs, each with a single function accessible to the
      diagnostician. By observing the march of epileptic seizures he developed the idea
      of somatotopic representation. He claimed that the nervous system is an
      evolutionary hierarchy of three levels connected by the process of weighted
      ordinal representation. His assertion of the Doctrine of Concomitance further
      separated the concerns, and the institutions, of the neurophysiologist from that
      of the psychiatrist. He came to reject the idea of the unconscious because he
      could not observe unequivocally unconscious behaviour at the bedside. Each of
      these ideas emerged from contemporaneous scientific streams, but Hughlings
      Jackson was the one to incorporate them into practical medicine. These
      neurological ideas gave physicians the methods, tools, principles and structures
      with which to establish a new science of clinical neurology.

PMID- 21903732
TI  - The extraordinary in the ordinary.

PMID- 21903730
TI  - Parsing the effects violence exposure in early childhood: modeling developmental
      pathways.
AB  - OBJECTIVE: To prospectively examine pathways from early childhood violence
      exposure and trauma-related symptoms to school-age emotional health. METHODS: A
      longitudinal, birth cohort (N = 437) was assessed with parent reports of lifetime
      violence exposure and trauma-related symptoms at 3 years of age and later,
      internalizing and externalizing symptoms, and social competence at school age.
      RESULTS: Early family and neighborhood violence correlated significantly with
      early trauma-related symptoms and also significantly predicted school-age
      internalizing and externalizing symptoms and poorer competence, independent of
      sociodemographic risk and past-year violence exposure. Longitudinal pathways were
      significantly mediated by arousal and avoidance symptoms at 3 years of age, which
      increased risk for clinically significant emotional problems and lower competence
      at school age (adjusted odds ratios = 3.1-6.1, p < 0.01). CONCLUSIONS: Trauma
      related symptoms may mediate developmental pathways from early violence exposure
      to later emotional health. Interventions that prevent or reduce early trauma
      related symptoms may ameliorate the long-term deleterious impact of violence
      exposure.

PMID- 21903733
TI  - Learning: what matters most.

PMID- 21903731
TI  - Roles of mutation and selection in speciation: from Hugo de Vries to the modern
      genomic era.
AB  - One of the most important problems in evolutionary biology is to understand how
      new species are generated in nature. In the past, it was difficult to study this
      problem because our lifetime is too short to observe the entire process of
      speciation. In recent years, however, molecular and genomic techniques have been
      developed for identifying and studying the genes involved in speciation. Using
      these techniques, many investigators have already obtained new findings. At
      present, however, the results obtained are complex and quite confusing. We have
      therefore attempted to understand these findings coherently with a historical
      perspective and clarify the roles of mutation and natural selection in
      speciation. We have first indicated that the root of the currently burgeoning
      field of plant genomics goes back to Hugo de Vries, who proposed the mutation
      theory of evolution more than a century ago and that he unknowingly found the
      importance of polyploidy and chromosomal rearrangements in plant speciation. We
      have then shown that the currently popular Dobzhansky-Muller model of evolution
      of reproductive isolation is only one of many possible mechanisms. Some of them
      are Oka's model of duplicate gene mutations, multiallelic speciation, mutation
      rescue model, segregation-distorter gene model, heterochromatin-associated
      speciation, single-locus model, etc. The occurrence of speciation also depends on
      the reproductive system, population size, bottleneck effects, and environmental
      factors, such as temperature and day length. Some authors emphasized the
      importance of natural selection to speed up speciation, but mutation is crucial
      in speciation because reproductive barriers cannot be generated without
      mutations.

PMID- 21903734
TI  - Hospital admission for rheumatoid arthritis dwindled in Italy between 2001 and
      2008.

PMID- 21903735
TI  - Percutaneous catheter decompression in the treatment of elevated intraabdominal
      pressure.
AB  - BACKGROUND: Intraabdominal hypertension (IAH) and abdominal compartment syndrome
      (ACS) traditionally have been treated surgically through emergent laparotomy.
      Intensivist-performed bedside drainage of free intraperitoneal fluid or blood
      (percutaneous catheter decompression [PCD]) has been advocated as a less-invasive
      alternative to open abdominal decompression (OAD). METHODS: A single-center
      disease and severity of illness-matched case-control comparison of 62 patients
      with IAH/ACS treated with PCD vs traditional OAD was performed. The relative
      efficacy of each treatment in reducing elevated intraabdominal pressure (IAP) and
      improving organ dysfunction was assessed. Physiologic and demographic predictors
      of successful PCD therapy were determined. RESULTS: PCD and OAD both were
      effective in significantly decreasing IAP and peak inspiratory pressure as well
      as in increasing abdominal perfusion pressure. PCD potentially avoided the need
      for subsequent OAD in 25 of 31 patients (81%) treated. Successful PCD therapy was
      associated with fluid drainage of > 1,000 mL or a decrease in IAP of > 9 mm Hg in
      the first 4 h postdecompression. CONCLUSIONS: Intensivist-performed PCD is an
      effective and less-invasive technique for treating patients with IAH/ACS where
      free intraperitoneal fluid or blood is present as determined by bedside
      ultrasonography. Failure to drain at least 1,000 mL of fluid and decrease IAP by
      at least 9 mm Hg in the first 4 h postdecompression is associated with PCD
      failure and should prompt urgent OAD.

PMID- 21903736
TI  - Sleep-disordered breathing and excessive daytime sleepiness in patients with
      atrial fibrillation.
AB  - BACKGROUND: An important consequence of sleep-disordered breathing (SDB) is
      excessive daytime sleepiness (EDS). EDS often predicts a favorable response to
      treatment of SDB, although in the setting of cardiovascular disease, particularly
      heart failure, SDB and EDS do not reliably correlate. Atrial fibrillation (AF) is
      another highly prevalent condition strongly associated with SDB. We sought to
      assess the relationship between EDS and SDB in patients with AF. METHODS: We
      conducted a prospective study of 151 patients referred for direct current
      cardioversion for AF who also underwent sleep evaluation and nocturnal
      polysomnography. The Epworth Sleepiness Scale (ESS) was administered prior to
      polysomnography and considered positive if the score was >= 11. The apnea
      hypopnea index (AHI) was tested for correlation with the ESS, with a cutoff of >=
      5 events/h for the diagnosis of SDB. RESULTS: Among the study participants, mean
      age was 69.1 +/- 11.7 years, mean BMI was 34.1 +/- 8.4 kg/m(2), and 76% were men.
      The prevalence of SDB in this population was 81.4%, and 35% had EDS. The
      association between ESS score and AHI was low (R(2) = 0.014, P = .64). The
      sensitivity and specificity of the ESS for the detection of SDB in patients with
      AF were 32.2% and 54.5%, respectively. CONCLUSIONS: Despite a high prevalence of
      SDB in this population with AF, most patients do not report EDS. Furthermore, EDS
      does not appear to correlate with severity of SDB or to accurately predict the
      presence of SDB. Further research is needed to determine whether EDS affects the
      natural history of AF or modifies the response to SDB treatment.

PMID- 21903738
TI  - Early ICU energy deficit is a risk factor for Staphylococcus aureus ventilator
      associated pneumonia.
AB  - BACKGROUND: Caloric insufficiency during the first week of ICU stay has been
      associated with increased infection rates. The connection between specific
      pathogens and host nutritional status in the ICU is not well known. This study
      was undertaken to determine the impact of patients' early in-ICU energy balance
      on the pathogens responsible for ventilator-associated pneumonia (VAP). METHODS:
      In this prospective, observational, cohort study conducted in a teaching hospital
      ICU, energy balance (energy delivered - calculated resting energy expenditure)
      was compared according to the microbiologic results of the fiber-optic BAL
      cultures of 76 consecutive patients receiving acute prolonged (>= 96 h)
      mechanical ventilation who developed VAP during their ICU stay. RESULTS: Among
      the 76 BAL cultures, 22 contained significant Staphylococcus aureus
      concentrations. The cumulated energy deficit of patients with S aureus VAP was
      greater than those with VAP caused by other pathogens (-10,275 +/- 4,211 kcal vs 
      7,376 +/- 4,013 kcal from ICU admission to day of BAL, P < .01). ICU admission,
      nutritional status, and conditions potentially limiting feeding did not differ
      significantly between the two groups. Patients with S aureus VAP had lower
      prescribed and delivered energy, causing higher energy deficits. Multivariate
      analysis identified energy deficit as being independently associated with S
      aureus VAP. More-severe energy deficit and higher rate of S aureus-positive BAL
      cultures (P = .01 comparing quartiles) were observed. CONCLUSIONS: Early ICU
      energy deficit is an independent determinant for acquiring S aureus VAP in
      patients on acute prolonged mechanical ventilation.

PMID- 21903737
TI  - Efficacy of aclidinium bromide 400 MUg twice daily compared with placebo and
      tiotropium in patients with moderate to severe COPD.
AB  - BACKGROUND: The efficacy and safety of aclidinium bromide bid, a novel, long
      acting, muscarinic antagonist, was assessed in patients with moderate to severe
      COPD. METHODS: In this phase IIa randomized, double-blind, double-dummy,
      crossover trial, patients with moderate to severe COPD received aclidinium 400
      MUg bid, tiotropium 8 MUg once daily, and placebo for 15 days, with a 9- to 15
      day washout between treatment periods. Treatments were administered through the
      Genuair or HandiHaler dry powder inhalers. The primary end point was mean change
      from baseline in FEV(1) AUC(0-12/12h) (area under the curve where the numbers
      represent the time period for which data were collected divided by the number of
      hours over which the data are averaged [eg, 0-12 h postdose divided by 12 h]) on
      day 15. Secondary end points were changes from baseline in FEV(1) AUC(12-24/12h),
      FEV(1) AUC(0-24/24h), morning predose FEV(1), peak FEV(1), and COPD symptom
      scores. RESULTS: Thirty patients with COPD were randomized, and 27 completed the
      study. Mean change from baseline in FEV(1) AUC(0-12/12h) at day 15 was
      significantly greater for aclidinium and tiotropium over placebo (P < .0001).
      Mean changes from baseline in FEV(1) AUC(12-24/12h), FEV(1) AUC(0-24/24h),
      morning predose FEV(1), and peak FEV(1) at day 15 were significantly greater for
      aclidinium and tiotropium over placebo (P < .0001 for all except P < .001 for
      FEV(1) AUC(12-24/12h) tiotropium vs placebo). Improvements were significantly
      greater with aclidinium vs tiotropium on day 1 for all of the normalized AUC
      values of FEV(1) as well as on day 15 for FEV(1) AUC(12-24/12h) (P < .05 for
      all). COPD symptoms were significantly improved from baseline with aclidinium vs
      placebo (P < .05) but not with tiotropium. CONCLUSIONS: In patients with COPD,
      aclidinium 400 MUg bid compared with placebo provided clinically meaningful
      improvements in 24-h bronchodilation that generally were comparable to tiotropium
      18 MUg daily but with significant differences in favor of aclidinium observed in
      the average nighttime period. Larger studies with longer treatment duration are
      ongoing to confirm the efficacy of aclidinium 400 MUg bid on bronchodilation and
      COPD symptoms. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00868231; URL:
      www.clinicaltrials.gov.

PMID- 21903739
TI  - Between-patient and within-patient (site-to-site) variability in estrogen
      receptor binding, measured in vivo by 18F-fluoroestradiol PET.
AB  - Heterogeneity of estrogen receptor (ER) expression may be an important predictor
      of breast cancer therapeutic response. (18)F-fluoroestradiol PET produces in vivo
      quantitative measurements of regional estrogen binding in breast cancer tumors.
      We describe within-patient (site-to-site) and between-patient heterogeneity of
      lesions in patients scheduled to receive endocrine therapy. METHODS: In 91
      patients with a prior ER-positive biopsy, 505 lesions were analyzed for both
      (18)F-fluoroestradiol and (18)F-FDG uptake and the (18)F-fluoroestradiol/(18)F
      FDG uptake ratio. Standardized uptake values (SUVs) were recorded for up to 16
      lesions per patient, of 1.5 cm or more and visible on (18)F-FDG PET or
      conventional staging. Linear mixed-effects regression models examined
      associations between PET parameters and patient or lesion characteristics and
      estimated variance components. A reader study of SUV measurements for 9 scans
      further examined sources of within-patient variability. RESULTS: Average (18)F
      fluoroestradiol uptake and (18)F-fluoroestradiol/(18)F-FDG ratio varied greatly
      across these patients, despite a history of ER-positive disease: about 37% had
      low or absent (18)F-fluoroestradiol uptake even with marked (18)F-FDG uptake.
      (18)F-fluoroestradiol SUV and (18)F-fluoroestradiol/(18)F-FDG ratio measurements
      within patients with multiple lesions were clustered around the patient's average
      value in most cases. Summarizing these findings, the intraclass correlation
      coefficient (proportion of total variation that is between-patient) was 0.60 (95%
      confidence interval, 0.50-0.69) for (18)F-fluoroestradiol SUV and 0.65 (95%
      confidence interval, 0.56-0.73) for the (18)F-fluoroestradiol/(18)F-FDG ratio.
      Some within-patient variation in PET measures (22%-44%) was attributable to
      interobserver variability as measured by the reader study. A subset of patients
      had mixed uptake, with widely disparate (18)F-fluoroestradiol SUV or (18)F
      fluoroestradiol/(18)F-FDG ratio for lesions in the same scan. CONCLUSION: (18)F
      fluoroestradiol uptake and the (18)F-fluoroestradiol/(18)F-FDG ratio varied
      greatly between patients but were usually consistent across lesions in the same
      scan. The average (18)F-fluoroestradiol SUV and (18)F-fluoroestradiol/(18)F-FDG
      ratio for a limited sample of lesions appear to provide a reasonable summary of
      synchronous ER expression for most patients. However, imaging the entire disease
      burden remains important to identify the subset of patients with mixed uptake,
      who may be at a critical point in their disease evolution.

PMID- 21903740
TI  - Contribution of PET/CT to prediction of outcome in children and young adults with
      rhabdomyosarcoma.
AB  - The purpose of this retrospective study was to evaluate the role of (18)F-FDG PET
      or PET/CT in the prediction of patient outcome in children and young adults
      affected by rhabdomyosarcoma. METHODS: Forty-one patients with histology-proven
      rhabdomyosarcoma who underwent PET or PET/CT were identified (age range, 1-20 y;
      mean age +/- SD, 9.9 +/- 5.8 y). Tumor maximum standardized uptake value
      (SUV(max)) and visually rated metabolic activity, as well as the presence of
      metabolically active lymph nodes and distant metastases, were compared with event
      free and overall survival. Multivariate Cox regression analyses were performed to
      compare the prediction of outcome according to metabolic tumor intensity in
      relation to established prognostic factors. RESULTS: Kaplan-Meier analyses
      revealed a significantly shorter overall survival in primary tumors visually
      rated as highly metabolically active or with a ratio of SUV(max) to SUV of the
      liver above 4.6. In addition, metabolically active lymph node and distant site
      involvement was indicative of significantly lower survival rates. On multivariate
      Cox regression analysis, the impact of intensity or SUV(max) of the primary tumor
      on outcome failed to attain significance, although PET performed better than some
      of the prognostic factors established in larger patient groups (P = 0.081).
      CONCLUSION: (18)F-FDG PET/CT is a valuable tool for initial staging in children
      affected by rhabdomyosarcoma. (18)F-FDG PET/CT may be an additional predictor of
      outcome and may be used to refine risk-adapted therapy. PET performed better than
      some established risk factors. The borderline significance level of primary tumor
      metabolism in multivariate testing may be an effect of the limited sample size.
      Further prospective evaluations are warranted.

PMID- 21903741
TI  - Molecular imaging with 11C-PD153035 PET/CT predicts survival in non-small cell
      lung cancer treated with EGFR-TKI: a pilot study.
AB  - Outcomes are suboptimal when molecularly targeted therapies are used in patient
      populations unselected for the molecular target. This pilot study examines the
      correlation of PET using (11)C-labeled 4-N-(3-bromoanilino)-6,7
      dimethoxyquinazoline ((11)C-PD153035), an imaging biomarker of epidermal growth
      factor receptor (EGFR), with outcomes in patients with non-small cell lung cancer
      (NSCLC) treated with the EGFR tyrosine kinase inhibitor erlotinib. METHODS:
      Patients with advanced chemotherapy-refractory NSCLC were prospectively enrolled
      on a trial of erlotinib at a dose of 150 mg daily and imaged by (11)C-PD153035
      PET/CT at baseline, after 1-2 wk, and after 6 wk from the start of treatment.
      Overall survival and progression-free survival (OS and PFS, respectively) times
      were correlated with the (11)C-PD153035 standardized uptake value (SUV) at each
      of the imaging times. RESULTS: Twenty-one patients were enrolled. Follow-up to
      progression was complete in all patients and to death in 18 of 21. By Cox
      regression analysis, baseline maximum SUV correlated strongly with OS and PFS
      (hazard ratio = 0.40, P = 0.002, and hazard ratio = 0.044, P < 0.001,
      respectively) independent of histology. Patients with higher maximum SUV
      (>=median) survived more than twice as long as patients with lower maximum SUV
      (median OS = 11.4 vs. 4.6 mo, P = 0.002; PFS = 4.4 vs. 1.8 mo, P < 0.001).
      However, (11)C-PD153035 uptake on follow-up scans was less well correlated with
      survival. CONCLUSION: Our preliminary results suggest (11)C-PD153035 PET/CT may
      be a noninvasive and rapid method for identifying patients with refractory
      advanced NSCLC of adenocarcinoma or squamous histology likely to respond to the
      EGFR tyrosine kinase inhibitor but not for monitoring treatment response.

PMID- 21903742
TI  - Widespread signatures of recent selection linked to nucleosome positioning in the
      human lineage.
AB  - In this study we investigated the strengths and modes of selection associated
      with nucleosome positioning in the human lineage through the comparison of
      interspecies and intraspecies rates of divergence. We identify significant
      evidence for both positive and negative selection linked to human nucleosome
      positioning for the first time, implicating a widespread and important role for
      DNA sequence in the location of well-positioned nucleosomes. Selection appears to
      be acting on particular base substitutions to maintain optimum GC compositions in
      core and linker regions, with, e.g., unexpectedly elevated rates of C->T
      substitutions during recent human evolution at linker regions 60-90 bp from the
      nucleosome dyad but significant depletion of the same substitutions within
      nucleosome core regions. These patterns are strikingly consistent with the known
      relationships between genomic sequence composition and nucleosome assembly. By
      stratifying nucleosomes according to the GC content of their genomic
      neighborhood, we also show that the strength and direction of selection detected
      is dictated by local GC content. Intriguingly these signatures of selection are
      not restricted to nucleosomes in close proximity to exons, suggesting the correct
      positioning of nucleosomes is not only important in and around coding regions.
      This analysis provides strong evidence that the genomic sequences associated with
      nucleosomes are not evolving neutrally, and suggests that underlying DNA sequence
      is an important factor in nucleosome positioning. Recent signatures of selection
      linked to genomic features as ubiquitous as the nucleosome have important
      implications for human genome evolution and disease.

PMID- 21903743
TI  - Differential expression in RNA-seq: a matter of depth.
AB  - Next-generation sequencing (NGS) technologies are revolutionizing genome
      research, and in particular, their application to transcriptomics (RNA-seq) is
      increasingly being used for gene expression profiling as a replacement for
      microarrays. However, the properties of RNA-seq data have not been yet fully
      established, and additional research is needed for understanding how these data
      respond to differential expression analysis. In this work, we set out to gain
      insights into the characteristics of RNA-seq data analysis by studying an
      important parameter of this technology: the sequencing depth. We have analyzed
      how sequencing depth affects the detection of transcripts and their
      identification as differentially expressed, looking at aspects such as transcript
      biotype, length, expression level, and fold-change. We have evaluated different
      algorithms available for the analysis of RNA-seq and proposed a novel approach-
      NOISeq--that differs from existing methods in that it is data-adaptive and
      nonparametric. Our results reveal that most existing methodologies suffer from a
      strong dependency on sequencing depth for their differential expression calls and
      that this results in a considerable number of false positives that increases as
      the number of reads grows. In contrast, our proposed method models the noise
      distribution from the actual data, can therefore better adapt to the size of the
      data set, and is more effective in controlling the rate of false discoveries.
      This work discusses the true potential of RNA-seq for studying regulation at low
      expression ranges, the noise within RNA-seq data, and the issue of replication.

PMID- 21903744
TI  - Randomized trial of an internet-based computer-tailored expert system for
      physical activity in patients with heart disease.
AB  - BACKGROUND: The CardioFit Internet-based expert system was designed to promote
      physical activity in patients with coronary heart disease (CHD) who were not
      participating in cardiac rehabilitation. DESIGN: This randomized controlled trial
      compared CardioFit to usual care to assess its effects on physical activity
      following hospitalization for acute coronary syndromes. METHODS: A total of 223
      participants were recruited at the University of Ottawa Heart Institute or London
      Health Sciences Centre and randomly assigned to either CardioFit (n = 115) or
      usual care (n = 108). The CardioFit group received a personally tailored physical
      activity plan upon discharge from the hospital and access to a secure website for
      activity planning and tracking. They completed five online tutorials over a 6
      month period and were in email contact with an exercise specialist. Usual care
      consisted of physical activity guidance from an attending cardiologist. Physical
      activity was measured by pedometer and self-reported over a 7-day period, 6 and
      12 months after randomization. RESULTS: The CardioFit Internet-based physical
      activity expert system significantly increased objectively measured (p = 0.023)
      and self-reported physical activity (p = 0.047) compared to usual care. Emotional
      (p = 0.038) and physical (p = 0.031) dimensions of heart disease health-related
      quality of life were also higher with CardioFit compared to usual care.
      CONCLUSIONS: Patients with CHD using an Internet-based activity prescription with
      online coaching were more physically active at follow up than those receiving
      usual care. Use of the CardioFit program could extend the reach of rehabilitation
      and secondary-prevention services.

PMID- 21903746
TI  - RTOG 94-10: keenly awaited results validating the best therapeutic strategy for
      locally advanced non-small cell lung cancer.

PMID- 21903745
TI  - Sequential vs. concurrent chemoradiation for stage III non-small cell lung
      cancer: randomized phase III trial RTOG 9410.
AB  - BACKGROUND: The combination of chemotherapy with thoracic radiotherapy (TRT)
      compared with TRT alone has been shown to confer a survival advantage for good
      performance status patients with stage III non-small cell lung cancer. However,
      it is not known whether sequential or concurrent delivery of these therapies is
      the optimal combination strategy. METHODS: A total of 610 patients were randomly
      assigned to two concurrent regimens and one sequential chemotherapy and TRT
      regimen in a three-arm phase III trial. The sequential arm included cisplatin at
      100 mg/m2 on days 1 and 29 and vinblastine at 5 mg/m2 per week for 5 weeks with
      63 Gy TRT delivered as once-daily fractions beginning on day 50. Arm 2 used the
      same chemotherapy regimen as arm 1 with 63 Gy TRT delivered as once-daily
      fractions beginning on day 1 [corrected]. Arm 3 used cisplatin at 50 mg/m2 on
      days 1, 8, 29, and 36 with oral etoposide at 50 mg twice daily for 10 weeks on
      days 1, 2, 5, and 6 with 69.6 Gy delivered as 1.2 Gy twice-daily fractions
      beginning on day 1. The primary endpoint was overall survival, and secondary
      endpoints included tumor response and time to tumor progression. Kaplan-Meier
      analyses were used to assess survival, and toxic effects were examined using the
      Wilcoxon rank sum test. All statistical tests were two-sided. RESULTS: Median
      survival times were 14.6, 17.0, and 15.6 months for arms 1-3, respectively. Five
      year survival was statistically significantly higher for patients treated with
      the concurrent regimen with once-daily TRT compared with the sequential treatment
      (5-year survival: sequential, arm 1, 10% [20 patients], 95% confidence interval
      [CI] = 7% to 15%; concurrent, arm 2, 16% [31 patients], 95% CI = 11% to 22%, P =
      .046; concurrent, arm 3, 13% [22 patients], 95% CI = 9% to 18%). With a median
      follow-up time of 11 years, the rates of acute grade 3-5 nonhematologic toxic
      effects were higher with concurrent than sequential therapy, but late toxic
      effects were similar. CONCLUSION: Concurrent delivery of cisplatin-based
      chemotherapy with TRT confers a long-term survival benefit compared with the
      sequential delivery of these therapies.

PMID- 21903747
TI  - A selective cysteinyl leukotriene receptor 2 antagonist blocks myocardial
      ischemia/reperfusion injury and vascular permeability in mice.
AB  - Cysteinyl leukotrienes (CysLTs) are potent inflammatory mediators that
      predominantly exert their effects by binding to cysteinyl leukotriene receptors
      of the G protein-coupled receptor family. CysLT receptor 2 (CysLT(2)R), expressed
      in endothelial cells of some vascular beds, has been implicated in a variety of
      cardiovascular functions. Endothelium-specific overexpression of human CysLT(2)R
      in transgenic mice (hEC-CysLT(2)R) greatly increases myocardial infarction
      damage. Investigation of this receptor, however, has been hindered by the lack of
      selective pharmacological antagonists. Here, we describe the characterization of
      3-(((3-carboxycyclohexyl)amino)carbonyl)-4-(3-(4-(4-phenoxybutoxy)phenyl)
      propoxy)benzoic acid (BayCysLT(2)) and explore the selective effects of this
      compound in attenuating myocardial ischemia/reperfusion damage and vascular
      leakage. Using a recently developed beta-galactosidase-beta-arrestin
      complementation assay for CysLT(2)R activity (Mol Pharmacol 79:270-278, 2011), we
      determined BayCysLT(2) to be ~20-fold more potent than the nonselective dual
      CysLT receptor 1 (CysLT(1)R)/CysLT(2)R antagonist 4-(((1R,2E,4E,6Z,9Z)-1-((1S)-4
      carboxy-1-hydroxybutyl)-2,4,6,9-pentadecatetraen-1-yl)thio)benzoic acid (Bay
      u9773) (IC(50) 274 nM versus 4.6 MUM, respectively). Intracellular calcium
      mobilization in response to cysteinyl leukotriene administration showed that
      BayCysLT(2) was >500-fold more selective for CysLT(2)R compared with CysLT(1)R.
      Intraperitoneal injection of BayCysLT(2) in mice significantly attenuated
      leukotriene D(4)-induced Evans blue dye leakage in the murine ear vasculature.
      BayCysLT(2) administration either before or after ischemia/reperfusion attenuated
      the aforementioned increased myocardial infarction damage in hEC-CysLT(2)R mice.
      Finally, decreased neutrophil infiltration and leukocyte adhesion molecule mRNA
      expression were observed in mice treated with antagonist compared with untreated
      controls. In conclusion, we present the characterization of a potent and
      selective antagonist for CysLT(2)R that is useful for discerning biological
      activities of this receptor.

PMID- 21903748
TI  - Serotonin receptor type 3 antagonists improve obesity-associated fatty liver
      disease in mice.
AB  - Obesity is a major cause for nonalcoholic fatty liver disease (NAFLD). Previous
      studies suggested that alterations in intestinal motility and permeability
      contribute to the development of NAFLD. Serotonin and serotonin receptor type 3
      (5-HT(3)R) are key factors in the regulation of intestinal motility and
      permeability. Therefore, we studied the effect of the 5-HT(3)R antagonists
      tropisetron and palonosetron on the development of NAFLD in leptin-deficient
      obese mice. Four-week-old ob/ob mice and lean controls were treated for 6 weeks
      orally with tropisetron or palonosetron at 0.2 mg/kg per day. We determined
      markers of liver damage and inflammation, portal endotoxin levels, and duodenal
      concentrations of serotonin, serotonin-reuptake transporter (SERT), occludin, and
      claudin-1. Tropisetron treatment significantly reduced liver fat content (-29%),
      liver inflammation (-56%), and liver cell necrosis (-59%) in ob/ob mice. The
      beneficial effects of tropisetron were accompanied by a decrease in plasma
      alanine aminotransferase and portal vein plasma endotoxin levels, an attenuation
      of enhanced MyD88 and tumor necrosis factor-alpha mRNA expression in the liver,
      and an increase of tight junction proteins in the duodenum. Tropisetron treatment
      also caused a reduction of elevated serotonin levels and an increase of SERT in
      the duodenum of ob/ob mice. Palonosetron had similar effects as tropisetron with
      regard to the reduction of liver fat and other parameters. Tropisetron and
      palonosetron are effective in attenuating NAFLD in a genetic mouse model of
      obesity. The effect involves the intestinal nervous system, resulting in a
      reduction of endotoxin influx into the liver and subsequently of liver
      inflammation and fat accumulation.

PMID- 21903750
TI  - Lipoproteins of Enterococcus faecalis: bioinformatic identification, expression
      analysis and relation to virulence.
AB  - Enterococcus faecalis is a ubiquitous bacterium that is capable of surviving in a
      broad range of natural environments, including the human host, as either a
      natural commensal or an opportunistic pathogen involved in severe hospital
      acquired infections. How such opportunistic pathogens cause fatal infections is
      largely unknown but it is likely that they are equipped with sophisticated
      systems to perceive external signals and interact with eukaryotic cells.
      Accordingly, being partially exposed at the cell exterior, some surface
      associated proteins are involved in several steps of the infection process. Among
      them are lipoproteins, representing about 25 % of the surface-associated
      proteins, which could play a major role in bacterial virulence processes. This
      review focuses on the identification of 90 lipoprotein-encoding genes in the
      genome of the E. faecalis V583 clinical strain and their putative roles, and
      provides a transcriptional comparison of microarray data performed in
      environmental conditions including blood and urine. Taken together, these data
      suggest a potential involvement of lipoproteins in E. faecalis virulence, making
      them serious candidates for vaccine production.

PMID- 21903749
TI  - Modeling diabetes disease progression and salsalate intervention in Goto-Kakizaki
      rats.
AB  - Type 2 diabetes mellitus (T2DM) arises owing to insulin resistance and beta-cell
      dysfunction. Chronic inflammation is widely identified as a cause of T2DM. The
      Goto-Kakizaki (GK) rat is a spontaneous rodent model for T2DM with chronic
      inflammation. The purpose of this study was to characterize diabetes progression
      in GK rats and evaluate the potential role of the anti-inflammatory agent
      salsalate. The GK rats were divided into control groups (n = 6) and salsalate
      treatment groups (n = 6), which were fed a salsalate-containing diet from 5 to 21
      weeks of age. Blood glucose and salicylate concentrations were measured once a
      week. Glucose concentrations showed a biphasic increase in which the first phase
      started at approximately 5 weeks, resulting in an increase by 15 to 25 mg/dl and
      a second phase at 14 to 15 weeks with an upsurge of more than 100 mg/dl. A
      mechanism-based model was proposed to describe the natural diabetes progression
      and salsalate pharmacodynamics by using a population method in S-ADAPT. Two
      transduction cascades were applied to mimic the two T2DM components: insulin
      resistance and beta-cell dysfunction. Salsalate suppressed both disease factors
      by a fraction of 0.622 on insulin resistance and 0.134 on beta-cell dysfunction.
      The substantial alleviation of diabetes by salsalate supports the hypothesis that
      chronic inflammation is a pathogenic factor of diabetes in GK rats. In addition,
      body weight and food intake were measured and further modeled by a mechanism
      based growth model. Modeling results suggest that salsalate reduces weight gain
      by enhancing metabolic rate and energy expenditure in both GK and Wister-Kyoto
      rats.

PMID- 21903751
TI  - The RSP_2889 gene product of Rhodobacter sphaeroides is a CueR homologue
      controlling copper-responsive genes.
AB  - Metal homeostasis is important in all living cells in order to provide sufficient
      amounts of metal ions for biological processes but to prevent toxic effects by
      excess amounts. Here we show that the gene product of RSP_2889 of the
      facultatively photosynthetic bacterium Rhodobacter sphaeroides is homologous to
      CueR, a regulator of copper metabolism in Escherichia coli and other bacteria.
      CueR binds to the promoter regions of genes for a copper-translocating ATPase and
      for a copper chaperone and is responsible for their high expression when cells
      are exposed to elevated levels of copper ions. While deletion of RSP_2889 has no
      significant effect on copper resistance, expression from a low-copy-number
      plasmid mediates increased sensitivity to copper.

PMID- 21903752
TI  - Lipidomics of Candida albicans biofilms reveals phase-dependent production of
      phospholipid molecular classes and role for lipid rafts in biofilm formation.
AB  - Candida albicans-associated bloodstream infections are linked to the ability of
      this yeast to form biofilms. In this study, we used lipidomics to compare the
      lipid profiles of C. albicans biofilms and planktonic cells, in early and mature
      developmental phases. Our results showed that significant differences exist in
      lipid composition in both developmental phases. Biofilms contained higher levels
      of phospholipid and sphingolipids than planktonic cells (nmol per g biomass,
      P<0.05 for all comparisons). In the early phase, levels of lipid in most classes
      were significantly higher in biofilms compared to planktonic cells (P<=0.05). The
      ratio of phosphatidylcholine to phosphatidylethanolamine was lower in biofilms
      compared to planktonic cells in both early (1.17 vs 2.52, P<=0.001) and late
      (2.34 vs 3.81, P<=0.001) developmental phases. The unsaturation index of
      phospholipids decreased with time, with this effect being particularly strong for
      biofilms. Inhibition of the biosynthetic pathway for sphingolipid [mannosyl
      diinositolphosphoryl ceramide, M(IP)2C] by myriocin or aureobasidin A, and
      disruption of the gene encoding inositolphosphotransferase (Ipt1p), abrogated the
      ability of C. albicans to form biofilms. The differences in lipid profiles
      between biofilms and planktonic Candida cells may have important implications for
      the biology and antifungal resistance of biofilms.

PMID- 21903753
TI  - The glgB-encoded glycogen branching enzyme is essential for glycogen accumulation
      in Corynebacterium glutamicum.
AB  - Corynebacterium glutamicum transiently accumulates glycogen as carbon capacitor
      during the early exponential growth phase in media containing carbohydrates. In
      some bacteria glycogen is synthesized by the consecutive action of ADP-glucose
      pyrophosphorylase (GlgC), glycogen synthase (GlgA) and glycogen branching enzyme
      (GlgB). GlgC and GlgA of C. glutamicum have been shown to be necessary for
      glycogen accumulation in this organism. However, although cg1381 has been
      annotated as the putative C. glutamicum glgB gene, cg1381 and its gene product
      have not been characterized and their role in transient glycogen accumulation has
      not yet been investigated. We show here that the cg1381 gene product of C.
      glutamicum catalyses the formation of alpha-1,6-glycosidic bonds in
      polysaccharides and thus represents a glycogen branching enzyme. RT-PCR
      experiments revealed glgB to be co-transcribed with glgE, probably encoding a
      maltosyltransferase. Promoter activity assays with the glgE promoter region
      revealed carbon-source-dependent expression of the glgEB operon. Characterization
      of the growth and glycogen content of glgB-deficient and glgB-overexpressing
      strains showed that the glycogen branching enzyme GlgB is essential for glycogen
      formation in C. glutamicum. Taken together these results suggest that an
      interplay of the enzymes GlgC, GlgA and GlgB is not essential for growth, but is
      required for synthesis of the transient carbon capacitor glycogen in C.
      glutamicum.

PMID- 21903754
TI  - Effect of new alleles of the histidine kinase gene ciaH on the activity of the
      response regulator CiaR in Streptococcus pneumoniae R6.
AB  - The two-component regulatory system CiaRH of Streptococcus pneumoniae affects
      beta-lactam susceptibility, autolysis, bacteriocin production, competence
      development, host colonization and virulence. The system was discovered in a
      screen for S. pneumoniae R6 mutants resistant to the beta-lactam antibiotic
      cefotaxime. A mutation in the histidine kinase gene ciaH led to this phenotype by
      enhancing CiaR-mediated gene expression. Additional mutations in ciaH have been
      described in other spontaneous beta-lactam-resistant mutants of S. pneumoniae R6,
      but their influence on CiaR-mediated gene regulation has not been determined.
      Likewise, altered ciaH alleles are present in clinical S. pneumoniae isolates,
      none of which had been characterized. These novel ciaH variants were introduced
      into S. pneumoniae R6 to measure their ability to activate CiaR-dependent
      regulation. The ciaH alleles from spontaneous mutants obtained in the laboratory
      increased the activity of CiaR-dependent promoters between four- and 26-fold,
      while variants from clinical strains were less effective, with a threefold
      activation at most. Accordingly, phenotypes associated with a hyperactive CiaRH
      system, beta-lactam resistance, and prevention of competence development, were
      far more pronounced in the laboratory mutants. Amino acid changes affecting CiaH
      function were positioned throughout the protein. Five of the most activating
      changes are located close to the conserved histidine and one in the
      extracytoplasmic sensor domain. The characterization of new alleles of ciaH
      expands the spectrum of CiaH variants, which may help to elucidate signal
      transduction of this important regulatory system. Our study also demonstrates
      that ciaH alleles overstimulating CiaR regulon expression are present in clinical
      isolates of S. pneumoniae.

PMID- 21903755
TI  - Identification of SagA as a novel vaccine target for the prevention of
      Enterococcus faecium infections.
AB  - Infections caused by multiresistant Gram-positive bacteria represent a major
      health burden in the community as well as in hospitalized patients. Enterococci,
      especially Enterococcus faecium, are well-known pathogens of hospitalized
      patients and are frequently linked with resistance against multiple antibiotics,
      which compromises effective therapy. Rabbit immune serum raised against heat
      killed E. faecium E155, a HiRECC clone, was used in an opsonophagocytic assay, an
      inhibition assay and a mouse bacteraemia model to identify targets of opsonic and
      protective antibodies. Serum against whole heat-killed bacteria was opsonic and
      recognized a protein of about 72 kDa that was abundantly secreted. This protein,
      identified as SagA by LC-ES-MS/MS, was expressed in Escherichia coli and
      purified. Rabbit serum raised against the purified protein showed opsonic killing
      activity that was inhibited by almost 100% using 100 ug purified protein ml(-1).
      In a mouse bacteraemia model, a statistically significant reduction of the colony
      counts in blood was shown with immune rabbit serum compared with preimmune serum
      using the homologous and a heterologous vancomycin-resistant enterococci (VRE)
      strain. These results indicate that SagA could be used as a promising vaccine
      target to treat and/or prevent VRE bacteraemia.

PMID- 21903756
TI  - Dual regulatory pathways of flagellar gene expression by ClpXP protease in
      enterohaemorrhagic Escherichia coli.
AB  - In enterobacteria such as Escherichia coli and Salmonella species, flagellar
      biogenesis is strictly dependent upon the master regulator flhDC. Here, we
      demonstrate that in enterohaemorrhagic E. coli (EHEC), the flagellar regulon is
      controlled by ClpXP, a member of the ATP-dependent protease family, through two
      pathways: (i) post-translational control of the FlhD/FlhC master regulator and
      (ii) transcriptional control of the flhDC operon. Both FlhD and FlhC proteins
      accumulated markedly following ClpXP depletion, and their half-lives were
      significantly longer in the mutant cells, suggesting that ClpXP is responsible
      for degrading FlhD and FlhC proteins, leading to downregulation of flagellar
      expression. ClpXP was involved in regulating the transcription of the flhD
      promoter only when the cells had entered stationary phase in a culture medium
      that markedly induced expression of the locus of enterocyte effacement (LEE).
      Comparative analyses of transcription from the flhD promoter in EHEC cells with
      different genetic backgrounds suggested that the downregulation of flhDC
      expression by ClpXP is dependent on the LEE-encoded GrlR-GrlA system. We have
      also shown that the degradation of FlhD and FlhC by ClpXP is responsible for
      downregulating flagellar expression even when LEE expression is induced.

PMID- 21903757
TI  - Reduction of quinones and phenoxy radicals by extracellular glucose dehydrogenase
      from Glomerella cingulata suggests a role in plant pathogenicity.
AB  - The plant-pathogenic fungus Glomerella cingulata (anamorph Colletotrichum
      gloeosporoides) secretes high levels of an FAD-dependent glucose dehydrogenase
      (GDH) when grown on tomato juice-supplemented media. To elucidate its molecular
      and catalytic properties, GDH was produced in submerged culture. The highest
      volumetric activity was obtained in shaking flasks after 6 days of cultivation
      (3400 U l-1, 4.2 % of total extracellular protein). GDH is a monomeric protein
      with an isoelectric point of 5.6. The molecular masses of the glycoforms ranged
      from 95 to 135 kDa, but after deglycosylation, a single 68 kDa band was obtained.
      The absorption spectrum is typical for an FAD-containing enzyme with maxima at
      370 and 458 nm and the cofactor is non-covalently bound. The preferred substrates
      are glucose and xylose. Suitable electron acceptors are quinones, phenoxy
      radicals, 2,6-dichloroindophenol, ferricyanide and ferrocenium
      hexafluorophosphate. In contrast, oxygen turnover is very low. The GDH-encoding
      gene was cloned and phylogenetic analysis of the translated protein reveals its
      affiliation to the GMC family of oxidoreductases. The proposed function of this
      quinone and phenoxy radical reducing enzyme is to neutralize the action of plant
      laccase, phenoloxidase or peroxidase activities, which are increased in infected
      plants to evade fungal attack.

PMID- 21903758
TI  - The Bdellovibrio bacteriovorus twin-arginine transport system has roles in
      predatory and prey-independent growth.
AB  - Bdellovibrio bacteriovorus grows in one of two ways: either (i) predatorily [in a
      host-dependent (HD) manner], when it invades the periplasm of another Gram
      negative bacterium, exporting into the prey co-ordinated waves of soluble enzymes
      using the prey cell contents for growth; or (ii) in a host-independent (HI)
      manner, when it grows (slowly) axenically in rich media. Periplasmic invasion
      potentially exposes B. bacteriovorus to extremes of pH and exposes the need to
      scavenge electron donors from prey electron transport components by synthesis of
      metalloenzymes. The twin-arginine transport system (Tat) in other bacteria
      transports folded metalloenzymes and the B. bacteriovorus genome encodes 21
      potential Tat-transported substrates and Tat transporter proteins TatA1, TatA2
      and TatBC. GFP tagging of the Tat signal peptide from Bd1802, a high-potential
      iron-sulfur protein (HiPIP), revealed it to be exported into the prey bacterium
      during predatory growth. Mutagenesis showed that the B. bacteriovorus tatA2 and
      tatC gene products are essential for both HI and HD growth, despite the fact that
      they partially complement (in SDS resistance assays) the corresponding mutations
      in Escherichia coli where neither TatA nor TatC are essential for life. The
      essentiality of B. bacteriovorus TatA2 was surprising given that the B.
      bacteriovorus genome encodes a second tatA homologue, tatA1. Transcription of
      tatA1 was found to be induced upon entry to the bdelloplast, and insertional
      inactivation of tatA1 showed that it significantly slowed the rates of both HI
      and HD growth. B. bacteriovorus is one of a few bacterial species that are
      reliant on a functional Tat system and where deletion of a single tatA1 gene
      causes a significant growth defect(s), despite the presence of its tatA2
      homologue.

PMID- 21903759
TI  - Circadian regulation of electrolyte absorption in the rat colon.
AB  - The intestinal transport of nutrients exhibits distinct diurnal rhythmicity, and
      the enterocytes harbor a circadian clock. However, temporal regulation of the
      genes involved in colonic ion transport, i.e., ion transporters and channels
      operating in absorption and secretion, remains poorly understood. To address this
      issue, we assessed the 24-h profiles of expression of genes encoding the sodium
      pump (subunits Atp1a1 and Atp1b1), channels (alpha-, beta-, and gamma-subunits of
      Enac and Cftr), transporters (Dra, Ae1, Nkcc1, Kcc1, and Nhe3), and the
      Na(+)/H(+) exchanger (NHE) regulatory factor (Nherf1) in rat colonic mucosa.
      Furthermore, we investigated temporal changes in the spatial localization of the
      clock genes Per1, Per2, and Bmal1 and the genes encoding ion transporters and
      channels along the crypt axis. In rats fed ad libitum, the expression of Atp1a1,
      gammaEnac, Dra, Ae1, Nhe3, and Nherf1 showed circadian variation with maximal
      expression at circadian time 12, i.e., at the beginning of the subjective night.
      The peak gammaEnac expression coincided with the rise in plasma aldosterone.
      Restricted feeding phase advanced the expression of Dra, Ae1, Nherf, and
      gammaEnac and decreased expression of Atp1a1. The genes Atp1b1, Cftr, alphaEnac,
      betaEnac, Nkcc1, and Kcc1 did not show any diurnal variations in mRNA levels. A
      low-salt diet upregulated the expression of betaEnac and gammaEnac during the
      subjective night but did not affect expression of alphaEnac. Similarly, colonic
      electrogenic Na(+) transport was much higher during the subjective night than the
      subjective day. These findings indicate that the transporters and channels
      operating in NaCl absorption undergo diurnal regulation and suggest a role of an
      intestinal clock in the coordination of colonic NaCl absorption.

PMID- 21903760
TI  - Depletion of gut commensal bacteria attenuates intestinal ischemia/reperfusion
      injury.
AB  - Gut commensal bacteria play important roles in the development and homeostasis of
      intestinal immunity. However, the role of gut commensals in intestinal
      ischemia/reperfusion (I/R) injury is unclear. To determine the roles of gut
      commensal bacteria in intestinal IR injury, we depleted gut microbiota with a
      broad-spectrum antibiotic cocktail and performed mesenteric I/R (M I/R). First,
      we confirmed that antibiotic treatment completely depleted gut commensal bacteria
      and diminished the size of secondary lymphoid tissues such as the Peyer's
      patches. We next found that antibiotic treatment attenuated intestinal injury
      following M I/R. Depletion of gut commensal bacteria reduced the expression of
      Toll-like receptor (TLR)2 and TLR4 in the intestine. Both are well-known
      receptors for gram-positive and -negative bacteria. Decreased expression of TLR2
      and TLR4 led to the reduction of inflammatory mediators, such as TNF, IL-6, and
      cyclooxygenase-2. Intestinal I/R injury is initiated when natural antibodies
      recognize neo-antigens that are revealed on ischemic cells and activate the
      complement pathway. Thus we evaluated complement and immunoglobulin (Ig)
      deposition in the damaged intestine and found that antibiotic treatment decreased
      the deposition of both C3 and IgM. Interestingly, we also found that the
      deposition of IgA also increased in the intestine following M I/R compared with
      control mice and that antibiotic treatment decreased the deposition of IgA in the
      damaged intestine. These results suggest that depletion of gut commensal bacteria
      decreases B cells, Igs, and TLR expression in the intestine, inhibits complement
      activation, and attenuates intestinal inflammation and injury following M I/R.

PMID- 21903762
TI  - Effect of esophageal contraction on esophageal wall blood perfusion.
AB  - Myocardial blood flow occurs during the diastolic phase of the cardiac cycle,
      because myocardial contraction during the systolic phase impedes myocardial
      perfusion. Using laser Doppler perfusion technique, we studied the effect of
      esophageal contraction on the esophageal wall perfusion. Studies were conducted
      in rats. A laser Doppler probe was anchored to the esophageal wall, and wall
      perfusion was studied under various experimental conditions. Increase and
      decrease in the systemic blood pressure induced by different pharmacological
      agents was associated with the increase and decrease in the esophageal wall
      perfusion, respectively. Esophageal contractions induced by electrical
      stimulation of the vagus nerve and electrical stimulation of the muscle directly
      resulted in a reduction in the esophageal wall perfusion, in a dose-dependent
      fashion. Esophageal wall perfusion could be monitored by placing the Doppler
      probe on the esophageal mucosa or on the outside of the esophageal wall.
      Esophageal contraction impedes entry of blood into the esophageal wall. Future
      studies may investigate if ischemia of the esophageal wall induced by sustained
      esophageal contractions/esophageal spasm is the cause of esophageal pain symptoms
      in humans.

PMID- 21903761
TI  - Wingless homolog Wnt11 suppresses bacterial invasion and inflammation in
      intestinal epithelial cells.
AB  - Wnt11 plays an essential role in gastrointestinal epithelial proliferation, and
      previous investigations have focused on development and immune responses.
      However, the roles of how enteric bacteria regulate Wnt11 and how Wnt11 modulates
      the host response to pathogenic bacteria remain unexplored. This study
      investigated the effects of Salmonella infection on Wnt activation in intestinal
      epithelial cells. We found that Wnt11 mRNA and protein expression were elevated
      after Salmonella colonization. Wnt11 protein secretion in epithelial cells was
      also elevated after bacterial infection. Furthermore, we demonstrated that
      pathogenic Salmonella regulated Wnt11 expression and localization in vivo. We
      found a decrease in Salmonella invasion in cells with Wnt11 overexpression
      compared with cells with normal Wnt11 level. IL-8 mRNA in Wnt11-transfected cells
      was low; however, it was enhanced in cells with a low level of Wnt11 expression.
      Functionally, Wnt11 overexpression inhibited Salmonella-induced apoptosis. AvrA
      is a known bacterial effector protein that stabilizes beta-catenin, the
      downstream regulator of Wnt signaling, and inhibits bacterially induced
      intestinal inflammation. We observed that Wnt11 expression, secretion, and
      transcriptional activity were regulated by Salmonella AvrA. Overall, Wnt11 is
      involved in the protection of the host intestinal cells by blocking the invasion
      of pathogenic bacteria, suppressing inflammation, and inhibiting apoptosis. Wnt11
      is a novel and important contributor to intestinal homeostasis and host defense.

PMID- 21903763
TI  - Castration inhibits biliary proliferation induced by bile duct obstruction: novel
      role for the autocrine trophic effect of testosterone.
AB  - Increased cholangiocyte growth is critical for the maintenance of biliary mass
      during liver injury by bile duct ligation (BDL). Circulating levels of
      testosterone decline following castration and during cholestasis. Cholangiocytes
      secrete sex hormones sustaining cholangiocyte growth by autocrine mechanisms. We
      tested the hypothesis that testosterone is an autocrine trophic factor
      stimulating biliary growth. The expression of androgen receptor (AR) was
      determined in liver sections, male cholangiocytes, and cholangiocyte cultures
      [normal rat intrahepatic cholangiocyte cultures (NRICC)]. Normal or BDL
      (immediately after surgery) rats were treated with testosterone or
      antitestosterone antibody or underwent surgical castration (followed by
      administration of testosterone) for 1 wk. We evaluated testosterone serum levels;
      intrahepatic bile duct mass (IBDM) in liver sections of female and male rats
      following the administration of testosterone; and secretin-stimulated cAMP levels
      and bile secretion. We evaluated the expression of 17beta-hydroxysteroid
      dehydrogenase 3 (17beta-HSD3, the enzyme regulating testosterone synthesis) in
      cholangiocytes. We evaluated the effect of testosterone on the proliferation of
      NRICC in the absence/presence of flutamide (AR antagonist) and antitestosterone
      antibody and the expression of 17beta-HSD3. Proliferation of NRICC was evaluated
      following stable knock down of 17beta-HSD3. We found that cholangiocytes and
      NRICC expressed AR. Testosterone serum levels decreased in castrated rats
      (prevented by the administration of testosterone) and rats receiving
      antitestosterone antibody. Castration decreased IBDM and secretin-stimulated cAMP
      levels and ductal secretion of BDL rats. Testosterone increased 17beta-HSD3
      expression and proliferation in NRICC that was blocked by flutamide and
      antitestosterone antibody. Knock down of 17beta-HSD3 blocks the proliferation of
      NRICC. Drug targeting of 17beta-HSD3 may be important for managing
      cholangiopathies.

PMID- 21903764
TI  - Pretreatment with the probiotic VSL#3 delays transition from inflammation to
      dysplasia in a rat model of colitis-associated cancer.
AB  - Evidence supports involvement of microflora in the transition of chronic
      inflammation to neoplasia. We investigated the protective efficacy of the
      probiotic VSL#3 in a model of colitis-associated colorectal cancer. Chronic
      colitis was induced in Sprague-Dawley rats by administration of trinitrobenzene
      sulfonic acid (TNBS), followed 6 wk later by systemic reactivation. To induce
      colitis-associated dysplasia and cancer, the animals received TNBS
      (intravenously) twice a week for 10 wk. One group received VSL#3 in drinking
      water from 1 wk before colitis induction until death. The colons were examined
      for damage and presence of dysplasia or cancer. Samples were analyzed for cell
      proliferation and apoptosis, vitamin D receptor (VDR) expression, angiogenic
      factors, and presence of alkaline sphingomyelinase or phosphatase. Microbial
      community composition was evaluated by terminal restriction fragment-length
      polymorphism analysis of the bacterial 16S rRNA gene. None of the probiotic
      treated animals developed carcinoma, and no high-grade dysplasia was found in
      either the proximal or mid colon. In contrast, 29% of the animals in the control
      group developed carcinoma in one or more regions of the colon. VSL#3-treated
      animals had significantly less damage than the vehicle treated-controls in all
      areas of the colon, and this correlated with decreased richness and diversity of
      the mucosally adherent microbiota. Treatment with the probiotic increased the
      antiangiogenic factor angiostatin, VDR expression, and alkaline sphingomyelinase.
      We concluded that pretreatment with the probiotic VSL#3 can attenuate various
      inflammatory-associated parameters, delaying transition to dysplasia and cancer,
      thus offering its potential therapeutic use in patients with long-standing
      colitis.

PMID- 21903765
TI  - Anti-inflammatory effects of Saccharomyces boulardii mediated by myeloid
      dendritic cells from patients with Crohn's disease and ulcerative colitis.
AB  - Saccharomyces boulardii (Sb) is a probiotic yeast that has demonstrated efficacy
      in pilot studies in patients with inflammatory bowel disease (IBD). Microbial
      antigen handling by dendritic cells (DC) is believed to be of critical importance
      for immunity and tolerance in IBD. The aim was to characterize the effects of Sb
      on DC from IBD patients. Highly purified (>95%), lipopolysaccharide-stimulated
      CD1c(+)CD11c(+)CD123(-) myeloid DC (mDC) from patients with ulcerative colitis
      (UC; n = 36), Crohn's disease (CD; n = 26), or infectious controls (IC; n = 4)
      were cultured in the presence or absence of fungal supernatant from Sb (SbS).
      Phenotype and cytokine production and/or secretion of IBD mDC were measured by
      flow cytometry and cytometric bead arrays, respectively. T cell phenotype and
      proliferation were assessed in a mixed lymphocyte reaction (MLR) with allogenic
      CD4(+)CD45RA(+) naive T cells from healthy donors. Mucosal healing was
      investigated in epithelial wounding and migration assays with IEC-6 cells. SbS
      significantly decreased the frequency of CD40-, CD80-, and CD197 (CCR7; chemokine
      receptor-7)-expressing IBD mDC and reduced their secretion of tumor necrosis
      factor (TNF)-alpha and interleukin (IL)-6 while increasing IL-8. In the MLR, SbS
      significantly inhibited T cell proliferation induced by IBD mDC. Moreover, SbS
      inhibited T(H)1 (TNF-alpha and interferon-gamma) polarization induced by UC mDC
      and promoted IL-8 and transforming growth factor-beta-dependent mucosal healing.
      In summary, we provide novel evidence of synergistic mechanisms how Sb controls
      inflammation (inhibition of T cell costimulation and inflammation-associated
      migration and mobilization of DC) and promotes epithelial restitution relevant in
      IBD.

PMID- 21903766
TI  - Ammonia reduction with ornithine phenylacetate restores brain eNOS activity via
      the DDAH-ADMA pathway in bile duct-ligated cirrhotic rats.
AB  - Ammonia is central in the pathogenesis of hepatic encephalopathy, which is
      associated with dysfunction of the nitric oxide (NO) signaling pathway. Ornithine
      phenylacetate (OP) reduces hyperammonemia and brain water in cirrhotic animals.
      This study aimed to determine whether endothelial NO synthase activity is altered
      in the brain of cirrhotic animals, whether this is associated with changes in the
      endogenous inhibitor, asymmetric-dimethylarginine (ADMA) and its regulating
      enzyme, dimethylarginine-dimethylaminohydrolase (DDAH-1), and whether these
      abnormalities are restored by ammonia reduction using OP. Sprague-Dawley rats
      were studied 4-wk after bile duct ligation (BDL) (n = 16) or sham operation (n =
      8) and treated with placebo or OP (0.6 g/kg). Arterial ammonia, brain water, TNF
      alpha, plasma, and brain ADMA were measured using standard techniques. NOS
      activity was measured radiometrically, and protein expression for NOS enzymes,
      ADMA, DDAH-1, 4-hydroxynonenol ((4)HNE), and NADPH oxidase (NOX)-1 were measured
      by Western blotting. BDL significantly increased arterial ammonia (P < 0.0001),
      brain water (P < 0.05), and brain TNF-alpha (P < 0.01). These were reduced
      significantly by OP treatment. The estimated eNOS component of constitutive NOS
      activity was significantly lower (P < 0.05) in BDL rat, and this was
      significantly attenuated in OP-treated animals. Brain ADMA levels were
      significantly higher and brain DDAH-1 significantly lower in BDL compared with
      sham (P < 0.01) and restored toward normal following treatment with OP. Brain
      (4)HNE and NOX-1 protein expression were significantly increased in BDL rat
      brain, which were significantly decreased following OP administration. We show a
      marked abnormality of NO regulation in cirrhotic rat brains, which can be
      restored by reduction in ammonia concentration using OP.

PMID- 21903767
TI  - Inhibition of neurotensin receptor 1 selectively sensitizes prostate cancer to
      ionizing radiation.
AB  - Radiotherapy combined with androgen depletion is generally successful for
      treating locally advanced prostate cancer. However, radioresistance that
      contributes to recurrence remains a major therapeutic problem in many patients.
      In this study, we define the high-affinity neurotensin receptor 1 (NTR1) as a
      tractable new molecular target to radiosensitize prostate cancers. The selective
      NTR1 antagonist SR48692 sensitized prostate cancer cells in a dose- and time
      dependent manner, increasing apoptotic cell death and decreasing clonogenic
      survival. The observed cancer selectivity for combinations of SR48692 and
      radiation reflected differential expression of NTR1, which is highly expressed in
      prostate cancer cells but not in normal prostate epithelial cells.
      Radiosensitization was not affected by androgen dependence or androgen receptor
      expression status. NTR1 inhibition in cancer cell-attenuated epidermal growth
      factor receptor activation and downstream signaling, whether induced by
      neurotensin or ionizing radiation, establish a molecular mechanism for
      sensitization. Most notably, SR48692 efficiently radiosensitized PC-3M orthotopic
      human tumor xenografts in mice, and significantly reduced tumor burden. Taken
      together, our findings offer preclinical proof of concept for targeting the NTR1
      receptor as a strategy to improve efficacy and outcomes of prostate cancer
      treatments using radiotherapy.

PMID- 21903768
TI  - Long-lived inflammatory signaling in irradiated bone marrow is genome dependent.
AB  - Ionizing radiation is carcinogenic, but genotype is a key determinant of
      susceptibility. Mutational DNA damage is generally attributed to cause disease,
      but irradiation also affects multicellular interactions as a result of poorly
      understood bystander effects that may influence carcinogenic susceptibility. In
      this study, we show that the bone marrow of irradiated mice will retain the
      ability to kill hemopoietic clonogenic stem cells and to induce chromosomal
      instability for up to 3 months after irradiation. Chromosomal instability was
      induced in bone marrow cells derived from CBA/Ca mice, a strain that is
      susceptible to radiation-induced acute myeloid leukemia (r-AML), but not in
      C57BL6 mice that are resistant to r-AML. Similarly, clonogenic cell lethality was
      exhibited in C57BL/6 mice but not CBA/Ca mice. Mechanistic investigations
      revealed that these genotype-dependent effects involved cytokine-mediated
      signaling and were mediated by a cyclooxygenase-2-dependent mechanism. Thus, our
      results suggested that inflammatory processes were responsible for mediating and
      sustaining the durable effects of ionizing radiation observed on bone marrow
      cells. Because most exposures to ionizing radiation are directed to only part of
      the body, our findings imply that genotype-directed tissue responses may be
      important determinants of understanding the specific consequence of radiation
      exposure in different individuals.

PMID- 21903769
TI  - Antitumor activity of the investigational proteasome inhibitor MLN9708 in mouse
      models of B-cell and plasma cell malignancies.
AB  - PURPOSE: The clinical success of the first-in-class proteasome inhibitor
      bortezomib (VELCADE) has validated the proteasome as a therapeutic target for
      treating human cancers. MLN9708 is an investigational proteasome inhibitor that,
      compared with bortezomib, has improved pharmacokinetics, pharmacodynamics, and
      antitumor activity in preclinical studies. Here, we focused on evaluating the in
      vivo activity of MLN2238 (the biologically active form of MLN9708) in a variety
      of mouse models of hematologic malignancies, including tumor xenograft models
      derived from a human lymphoma cell line and primary human lymphoma tissue, and
      genetically engineered mouse (GEM) models of plasma cell malignancies (PCM).
      EXPERIMENTAL DESIGN: Both cell line-derived OCI-Ly10 and primary human lymphoma
      derived PHTX22L xenograft models of diffuse large B-cell lymphoma were used to
      evaluate the pharmacodynamics and antitumor effects of MLN2238 and bortezomib.
      The iMyc(Calpha)/Bcl-X(L) GEM model was used to assess their effects on de novo
      PCM and overall survival. The newly developed DP54-Luc-disseminated model of
      iMyc(Calpha)/Bcl-X(L) was used to determine antitumor activity and effects on
      osteolytic bone disease. RESULTS: MLN2238 has an improved pharmacodynamic profile
      and antitumor activity compared with bortezomib in both OCI-Ly10 and PHTX22L
      models. Although both MLN2238 and bortezomib prolonged overall survival, reduced
      splenomegaly, and attenuated IgG2a levels in the iMyc(Calpha)/Bcl-X(L) GEM model,
      only MLN2238 alleviated osteolytic bone disease in the DP54-Luc model.
      CONCLUSIONS: Our results clearly showed the antitumor activity of MLN2238 in a
      variety of mouse models of B-cell lymphoma and PCM, supporting its clinical
      development. MLN9708 is being evaluated in multiple phase I and I/II trials.

PMID- 21903771
TI  - BCR-ABL transcript dynamics support the hypothesis that leukemic stem cells are
      reduced during imatinib treatment.
AB  - PURPOSE: Imatinib induces a durable response in most patients with Philadelphia
      chromosome-positive chronic myeloid leukemia, but it is currently unclear whether
      imatinib reduces the leukemic stem cell (LSC) burden, which may be an important
      step toward enabling safe discontinuation of therapy. In this article, we use
      mathematical models of BCR-ABL levels to make inferences on the dynamics of LSCs.
      EXPERIMENTAL DESIGN: Patients with at least 1 BCR-ABL transcript measurement on
      imatinib were included (N = 477). Maximum likelihood methods were used to test 3
      potential hypotheses of the dynamics of BCR-ABL transcripts on imatinib therapy:
      (i) monoexponential, in which there is little, if any, decline in BCR-ABL
      transcripts; (ii) biexponential, in which patients have a rapid initial decrease
      in BCR-ABL transcripts followed by a more gradual response; and (iii)
      triexponential, in which patients first exhibit a biphasic decline but then have
      a third phase when BCR-ABL transcripts increase rapidly. RESULTS: We found that
      most patients treated with imatinib exhibit a biphasic decrease in BCR-ABL
      transcript levels, with a rapid decrease during the first few months of
      treatment, followed by a more gradual decrease that often continues over many
      years. CONCLUSIONS: We show that the only hypothesis consistent with current data
      on progenitor cell turnover and with the long-term, gradual decrease in the BCR
      ABL levels seen in most patients is that these patients exhibit a continual,
      gradual reduction of the LSCs. This observation may explain the ability to
      discontinue imatinib therapy without relapse in some cases.

PMID- 21903770
TI  - Disruptive TP53 mutation is associated with aggressive disease characteristics in
      an orthotopic murine model of oral tongue cancer.
AB  - PURPOSE: To characterize tumor growth and metastatic potential in head and neck
      squamous cell carcinoma (HNSCC) cell lines in an orthotopic murine model of oral
      tongue cancer and to correlate TP53 mutation status with these findings.
      EXPERIMENTAL DESIGN: Cells from each of 48 HNSCC cell lines were orthotopically
      injected into the oral tongues of nude mice. Tumor volume, cervical lymph node
      metastasis, and mouse survival were recorded. Direct sequencing of the TP53 gene
      and Western blot analysis for the p53 protein after induction with 5-fluorouracil
      was conducted. Cell lines were categorized as either mutant TP53 or wild-type
      TP53, and lines with TP53 mutation were further categorized on the basis of type
      of mutation (disruptive or nondisruptive) and level of p53 protein expression.
      The behavior of tumors in these different groups was compared. RESULTS: These 48
      HNSCC cell lines showed a wide range of behavior from highly aggressive and
      metastatic to no tumor formation. Mice injected with cells harboring disruptive
      TP53 mutations had faster tumor growth, greater incidence of cervical lymph node
      metastasis, and shorter survival than mice injected with cells lacking these
      mutations. CONCLUSIONS: HNSCC cell lines display a wide spectrum of behavior in
      an orthotopic model of oral cancer. Cell lines with disruptive TP53 mutations are
      more aggressive in this system, corroborating clinical reports that have linked
      these mutations to poor patient outcome.

PMID- 21903773
TI  - A phase 2 trial of dasatinib in patients with advanced HER2-positive and/or
      hormone receptor-positive breast cancer.
AB  - PURPOSE: SRC-family kinases (SFK) are involved in numerous oncogenic signaling
      pathways. A phase 2 trial of dasatinib, a potent oral tyrosine kinase inhibitor
      of SFKs, was carried out in patients with human epidermal growth factor receptor
      2-positive (HER2+) and/or hormone receptor-positive (HR+) advanced breast cancer.
      EXPERIMENTAL DESIGN: Patients with measurable tumors and progression after
      chemotherapy and HER2 and/or HR-targeted agents in adjuvant or metastatic
      settings (maximum of two prior metastatic setting regimens) received twice daily
      dasatinib. Primary endpoint was Response Evaluation Criteria in Solid Tumors
      defined response rate. Secondary endpoints included toxicity and limited
      pharmacokinetics. RESULTS: Seventy patients (55 years median age) were treated,
      83% of HER2+ patients had received prior HER2-directed therapy, and 61% of HR+
      patients had received prior endocrine therapy in the advanced setting. Dasatinib
      starting dose was reduced from 100 to 70 mg twice daily to limit toxicity. Median
      therapy duration was 1.8 months in both dose groups and most discontinuations
      were due to progression. Of 69 evaluable patients, three had confirmed partial
      responses and six had stable disease for 16 weeks or more (disease control rate =
      13.0%); all nine of these tumors were HR+ (two were also HER2+). The most common
      drug-related toxicities were gastrointestinal complaints, headache, asthenia, and
      pleural effusion. Grade 3-4 toxicity occurred in 37% of patients and was
      comparable between doses; drug-related serious adverse events were less frequent
      with 70 mg twice daily than 100 mg twice daily. CONCLUSION: Limited single-agent
      activity was observed with dasatinib in patients with advanced HR+ breast cancer.

PMID- 21903772
TI  - Preclinical testing of PI3K/AKT/mTOR signaling inhibitors in a mouse model of
      ovarian endometrioid adenocarcinoma.
AB  - PURPOSE: Genetically engineered mouse (GEM) models of ovarian cancer that closely
      recapitulate their human tumor counterparts may be invaluable tools for
      preclinical testing of novel therapeutics. We studied murine ovarian endometrioid
      adenocarcinomas (OEA) arising from conditional dysregulation of canonical WNT and
      PI3K/AKT/mTOR pathway signaling to investigate their response to conventional
      chemotherapeutic drugs and mTOR or AKT inhibitors. EXPERIMENTAL DESIGN: OEAs were
      induced by injection of adenovirus expressing Cre recombinase (AdCre) into the
      ovarian bursae of Apc(flox/flox); Pten(flox/flox) mice. Tumor-bearing mice or
      murine OEA-derived cell lines were treated with cisplatin and paclitaxel, mTOR
      inhibitor rapamycin, or AKT inhibitors API-2 or perifosine. Treatment effects
      were monitored in vivo by tumor volume and bioluminescence imaging, in vitro by
      WST-1 proliferation assays, and in OEA tissues and cells by immunoblotting and
      immunostaining for levels and phosphorylation status of PI3K/AKT/mTOR signaling
      pathway components. RESULTS: Murine OEAs developed within 3 weeks of AdCre
      injection and were not preceded by endometriosis. OEAs responded to cisplatin +
      paclitaxel, rapamycin, and AKT inhibitors in vivo. In vitro studies showed that
      response to mTOR and AKT inhibitors, but not conventional cytotoxic drugs, was
      dependent on the status of PI3K/AKT/mTOR signaling. AKT inhibition in APC(
      )/Pten(-) tumor cells resulted in compensatory upregulation of ERK signaling.
      CONCLUSIONS: The studies show the utility of this GEM model of ovarian cancer for
      preclinical testing of novel PI3K/AKT/mTOR signaling inhibitors and provide
      evidence for compensatory signaling, suggesting that multiple rather than single
      agent targeted therapy will be more efficacious for treating ovarian cancers with
      activated PI3K/AKT/mTOR signaling.

PMID- 21903774
TI  - A new functional CYP3A4 intron 6 polymorphism significantly affects tacrolimus
      pharmacokinetics in kidney transplant recipients.
AB  - BACKGROUND: Tacrolimus (Tac) is a potent immunosuppressant with considerable
      toxicity. Tac pharmacokinetics varies between individuals and thus complicates
      its use in preventing rejection after kidney transplantation. This variability
      might be caused by genetic polymorphisms in metabolizing enzymes. METHODS: We
      used TaqMan analyses to evaluate the impact of a newly discovered CYP3A4
      (cytochrome P450, family 3, subfamily A, polypeptide 4) single-nucleotide
      polymorphism (SNP) (rs35599367C>T; CYP3A4*22) on Tac pharmacokinetics in 185
      renal transplant recipients who participated in an international randomized
      controlled clinical trial (fixed-dose, concentration-controlled study). RESULTS:
      The overall mean daily-dose requirement to reach the same predose Tac blood
      concentration was 33% lower for carriers of the T variant allele than for
      rs35599367CC patients (95% CI, -46% to -20%; P = 0.018). When combined with the
      *3 genotype of the CYP3A5 (cytochrome P450, family 3, subfamily A, polypeptide 5)
      gene, the rs35599367C>T SNP was also associated with a risk of supratherapeutic
      Tac concentrations (>15 MUg/L) during the first 3 days after surgery, with an
      odds ratio of 8.7 for carriers of the CYP3A4 T allele plus CYP3A5*3/*3 (P =
      0.027) and 4.2 for the CYP3A4 CC homozygotes plus CYP3A5*3/*3 (P = 0.002),
      compared with CYP3A4 CC homozygotes having 1 or 2 CYP3A5*1 alleles. The overall
      increase in the Tac dose-adjusted trough blood concentration was +179% for
      carriers of the CYP3A4 T allele with CYP3A5*3/*3 (P < 0.001), +101% for CYP3A4 CC
      homozygotes with CYP3A5*3/*3 (P < 0.001), and +64% for CYP3A4 T allele carriers
      with CYP3A5*1 (P = 0.020),compared with CYP3A4 CC homozygotes with CYP3A5*1.
      CONCLUSIONS: The CYP3A4 rs35599367C>T polymorphism is associated with a
      significantly altered Tac metabolism and therefore increases the risk of
      supratherapeutic Tac concentrations early after transplantation. Analysis of this
      CYP3A4*22 SNP may help in identifying patients at risk of Tac overexposure.

PMID- 21903776
TI  - 800,000 years of abrupt climate variability.
AB  - We constructed an 800,000-year synthetic record of Greenland climate variability
      based on the thermal bipolar seesaw model. Our Greenland analog reproduces much
      of the variability seen in the Greenland ice cores over the past 100,000 years.
      The synthetic record shows strong similarity with the absolutely dated speleothem
      record from China, allowing us to place ice core records within an absolute
      timeframe for the past 400,000 years. Hence, it provides both a stratigraphic
      reference and a conceptual basis for assessing the long-term evolution of
      millennial-scale variability and its potential role in climate change at longer
      time scales. Indeed, we provide evidence for a ubiquitous association between
      bipolar seesaw oscillations and glacial terminations throughout the Middle to
      Late Pleistocene.

PMID- 21903775
TI  - Live attenuated malaria vaccine designed to protect through hepatic CD8+ T cell
      immunity.
AB  - Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum
      (Pf) malaria in >=80% of recipients. Pf sporozoites (PfSPZ) administered by
      mosquito bites are the only immunogens shown to induce such protection in humans.
      Such protection is thought to be mediated by CD8(+) T cells in the liver that
      secrete interferon-gamma (IFN-gamma). We report that purified irradiated PfSPZ
      administered to 80 volunteers by needle inoculation in the skin was safe, but
      suboptimally immunogenic and protective. Animal studies demonstrated that
      intravenous immunization was critical for inducing a high frequency of PfSPZ
      specific CD8(+), IFN-gamma-producing T cells in the liver (nonhuman primates,
      mice) and conferring protection (mice). Our results suggest that intravenous
      administration of this vaccine will lead to the prevention of infection with Pf
      malaria.

PMID- 21903777
TI  - A major constituent of brown algae for use in high-capacity Li-ion batteries.
AB  - The identification of similarities in the material requirements for applications
      of interest and those of living organisms provides opportunities to use renewable
      natural resources to develop better materials and design better devices. In our
      work, we harness this strategy to build high-capacity silicon (Si) nanopowder
      based lithium (Li)-ion batteries with improved performance characteristics. Si
      offers more than one order of magnitude higher capacity than graphite, but it
      exhibits dramatic volume changes during electrochemical alloying and de-alloying
      with Li, which typically leads to rapid anode degradation. We show that mixing Si
      nanopowder with alginate, a natural polysaccharide extracted from brown algae,
      yields a stable battery anode possessing reversible capacity eight times higher
      than that of the state-of-the-art graphitic anodes.

PMID- 21903778
TI  - Synthesized light transients.
AB  - Manipulation of electron dynamics calls for electromagnetic forces that can be
      confined to and controlled over sub-femtosecond time intervals. Tailored
      transients of light fields can provide these forces. We report on the generation
      of subcycle field transients spanning the infrared, visible, and ultraviolet
      frequency regimes with a 1.5-octave three-channel optical field synthesizer and
      their attosecond sampling. To demonstrate applicability, we field-ionized krypton
      atoms within a single wave crest and launched a valence-shell electron wavepacket
      with a well-defined initial phase. Half-cycle field excitation and attosecond
      probing revealed fine details of atomic-scale electron motion, such as the
      instantaneous rate of tunneling, the initial charge distribution of a valence
      shell wavepacket, the attosecond dynamic shift (instantaneous ac Stark shift) of
      its energy levels, and its few-femtosecond coherent oscillations.

PMID- 21903779
TI  - An expanded palette of genetically encoded Ca2+ indicators.
AB  - Engineered fluorescent protein (FP) chimeras that modulate their fluorescence in
      response to changes in calcium ion (Ca(2+)) concentration are powerful tools for
      visualizing intracellular signaling activity. However, despite a decade of
      availability, the palette of single FP-based Ca(2+) indicators has remained
      limited to a single green hue. We have expanded this palette by developing blue,
      improved green, and red intensiometric indicators, as well as an emission
      ratiometric indicator with an 11,000% ratio change. This series enables improved
      single-color Ca(2+) imaging in neurons and transgenic Caenorhabditis elegans. In
      HeLa cells, Ca(2+) was imaged in three subcellular compartments, and, in
      conjunction with a cyan FP-yellow FP-based indicator, Ca(2+) and adenosine 5'
      triphosphate were simultaneously imaged. This palette of indicators paints the
      way to a colorful new era of Ca(2+) imaging.

PMID- 21903785
TI  - National Science Foundation. Big budget squeeze looms for major new facilities.

PMID- 21903780
TI  - Still vulnerable in 2011.

PMID- 21903786
TI  - Newsmaker interview: Rao Yi. Piqued Chinese dean throws down the gauntlet.
      Interview by Hao Xin.

PMID- 21903787
TI  - Avian influenza. Warning of H5N1 resurgence surprises community.

PMID- 21903788
TI  - Paleoanthropology. Skeletons present an exquisite paleo-puzzle.

PMID- 21903789
TI  - Profile: Lee Berger. Paleoanthropologist now rides high on a new fossil tide.

PMID- 21903790
TI  - Paleoanthropology. Little Foot, big mystery.

PMID- 21903791
TI  - Superheavy elements. Which way to the island?

PMID- 21903792
TI  - Low sperm counts may be preventable.

PMID- 21903793
TI  - Hope for graduate school childbirth policies.

PMID- 21903795
TI  - Moving USAID forward.

PMID- 21903796
TI  - Public health. Boosting health services research.

PMID- 21903797
TI  - Geophysics. Antarctic ice flow revealed.

PMID- 21903798
TI  - Chemistry. High-throughput discovery of new chemical reactions.

PMID- 21903799
TI  - Cell signaling. Getting to the heart of mechanotransduction.

PMID- 21903800
TI  - Evolution. Mother tongue and Y chromosomes.

PMID- 21903801
TI  - Neuroscience. How many cell types does it take to wire a brain?

PMID- 21903802
TI  - Visualizing uncertainty about the future.
AB  - We are all faced with uncertainty about the future, but we can get the measure of
      some uncertainties in terms of probabilities. Probabilities are notoriously
      difficult to communicate effectively to lay audiences, and in this review we
      examine current practice for communicating uncertainties visually, using examples
      drawn from sport, weather, climate, health, economics, and politics. Despite the
      burgeoning interest in infographics, there is limited experimental evidence on
      how different types of visualizations are processed and understood, although the
      effectiveness of some graphics clearly depends on the relative numeracy of an
      audience. Fortunately, it is increasingly easy to present data in the form of
      interactive visualizations and in multiple types of representation that can be
      adjusted to user needs and capabilities. Nonetheless, communicating deeper
      uncertainties resulting from incomplete or disputed knowledge--or from essential
      indeterminacy about the future--remains a challenge.

PMID- 21903803
TI  - A gene for an extended phenotype.
AB  - Manipulation of host behavior by parasites and pathogens has been widely
      observed, but the basis for these behaviors has remained elusive. Gypsy moths
      infected by a baculovirus climb to the top of trees to die, liquefy, and "rain"
      virus on the foliage below to infect new hosts. The viral gene that manipulates
      climbing behavior of the host was identified, providing evidence of a genetic
      basis for the extended phenotype.

PMID- 21903804
TI  - The endocast of MH1, Australopithecus sediba.
AB  - The virtual endocast of MH1 (Australopithecus sediba), obtained from high-quality
      synchrotron scanning, reveals generally australopith-like convolutional patterns
      on the frontal lobes but also some foreshadowing of features of the human frontal
      lobes, such as posterior repositioning of the olfactory bulbs. Principal
      component analysis of orbitofrontal dimensions on australopith endocasts (MH1,
      Sts 5, and Sts 60) indicates that among these, MH1 orbitofrontal shape and
      organization align most closely with human endocasts. These results are
      consistent with gradual neural reorganization of the orbitofrontal region in the
      transition from Australopithecus to Homo, but given the small volume of the MH1
      endocast, they are not consistent with gradual brain enlargement before the
      transition.

PMID- 21903805
TI  - A partial pelvis of Australopithecus sediba.
AB  - The fossil record of the hominin pelvis reflects important evolutionary changes
      in locomotion and parturition. The partial pelves of two individuals of
      Australopithecus sediba were reconstructed from previously reported finds and new
      material. These remains share some features with australopiths, such as large
      biacetabular diameter, small sacral and coxal joints, and long pubic rami. The
      specimens also share derived features with Homo, including more vertically
      oriented and sigmoid-shaped iliac blades, greater robusticity of the iliac body,
      sinusoidal anterior iliac borders, shortened ischia, and more superiorly oriented
      pubic rami. These derived features appear in a species with a small adult brain
      size, suggesting that the birthing of larger-brained babies was not driving the
      evolution of the pelvis at this time.

PMID- 21903806
TI  - Australopithecus sediba hand demonstrates mosaic evolution of locomotor and
      manipulative abilities.
AB  - Hand bones from a single individual with a clear taxonomic affiliation are scarce
      in the hominin fossil record, which has hampered understanding the evolution of
      manipulative abilities in hominins. Here we describe and analyze a nearly
      complete wrist and hand of an adult female [Malapa Hominin 2 (MH2)]
      Australopithecus sediba from Malapa, South Africa (1.977 million years ago). The
      hand presents a suite of Australopithecus-like features, such as a strong flexor
      apparatus associated with arboreal locomotion, and Homo-like features, such as a
      long thumb and short fingers associated with precision gripping and possibly
      stone tool production. Comparisons to other fossil hominins suggest that there
      were at least two distinct hand morphotypes around the Plio-Pleistocene
      transition. The MH2 fossils suggest that Au. sediba may represent a basal
      condition associated with early stone tool use and production.

PMID- 21903807
TI  - The foot and ankle of Australopithecus sediba.
AB  - A well-preserved and articulated partial foot and ankle of Australopithecus
      sediba, including an associated complete adult distal tibia, talus, and
      calcaneus, have been discovered at the Malapa site, South Africa, and reported in
      direct association with the female paratype Malapa Hominin 2. These fossils
      reveal a mosaic of primitive and derived features that are distinct from those
      seen in other hominins. The ankle (talocrural) joint is mostly humanlike in form
      and inferred function, and there is some evidence for a humanlike arch and
      Achilles tendon. However, Au. sediba is apelike in possessing a more gracile
      calcaneal body and a more robust medial malleolus than expected. These
      observations suggest, if present models of foot function are correct, that Au.
      sediba may have practiced a unique form of bipedalism and some degree of
      arboreality. Given the combination of features in the Au. sediba foot, as well as
      comparisons between Au. sediba and older hominins, homoplasy is implied in the
      acquisition of bipedal adaptations in the hominin foot.

PMID- 21903808
TI  - Australopithecus sediba at 1.977 Ma and implications for the origins of the genus
      Homo.
AB  - Newly exposed cave sediments at the Malapa site include a flowstone layer capping
      the sedimentary unit containing the Australopithecus sediba fossils. Uranium-lead
      dating of the flowstone, combined with paleomagnetic and stratigraphic analysis
      of the flowstone and underlying sediments, provides a tightly constrained date of
      1.977 +/- 0.002 million years ago (Ma) for these fossils. This refined dating
      suggests that Au. sediba from Malapa predates the earliest uncontested evidence
      for Homo in Africa.

PMID- 21903809
TI  - A simple, multidimensional approach to high-throughput discovery of catalytic
      reactions.
AB  - Transition metal complexes catalyze many important reactions that are employed in
      medicine, materials science, and energy production. Although high-throughput
      methods for the discovery of catalysts that would mirror related approaches for
      the discovery of medicinally active compounds have been the focus of much
      attention, these methods have not been sufficiently general or accessible to
      typical synthetic laboratories to be adopted widely. We report a method to
      evaluate a broad range of catalysts for potential coupling reactions with the use
      of simple laboratory equipment. Specifically, we screen an array of catalysts and
      ligands with a diverse mixture of substrates and then use mass spectrometry to
      identify reaction products that, by design, exceed the mass of any single
      substrate. With this method, we discovered a copper-catalyzed alkyne
      hydroamination and two nickel-catalyzed hydroarylation reactions, each of which
      displays excellent functional-group tolerance.

PMID- 21903810
TI  - Aeroelastic flutter produces hummingbird feather songs.
AB  - During courtship flights, males of some hummingbird species produce diverse
      sounds with tail feathers of varying shapes. We show that these sounds are
      produced by air flowing past a feather, causing it to aeroelastically flutter and
      generate flutter-induced sound. Scanning laser doppler vibrometery and high-speed
      video of individual feathers of different sizes and shapes in a wind tunnel
      revealed multiple vibratory modes that produce a range of acoustic frequencies
      and harmonic structures. Neighboring feathers can be aerodynamically coupled and
      flutter either at the same frequency, resulting in sympathetic vibrations that
      increase loudness, or at different frequencies, resulting in audible interaction
      frequencies. Aeroelastic flutter is intrinsic to stiff airfoils such as feathers
      and thus explains tonal sounds that are common in bird flight.

PMID- 21903811
TI  - Flight at low ambient humidity increases protein catabolism in migratory birds.
AB  - Although fat is the primary fuel for migratory flight in birds, protein is also
      used. Catabolism of tissue protein yields five times as much water per kilojoule
      as fat, and so one proposed function of protein catabolism is to maintain water
      balance during nonstop flights. To test the protein-for-water hypothesis, we flew
      Swainson's thrushes (Catharus ustulatus) in a climatic wind tunnel under high-
      and low-humidity conditions at 18 degrees C for up to 5 hours. Flight under dry
      conditions increased the rates of lean mass loss and endogenous water production
      and also increased plasma uric acid concentration. These data demonstrate that
      atmospheric humidity influences fuel composition in flight and suggest that
      protein deposition and catabolism during migration are, in part, a metabolic
      strategy to maintain osmotic homeostasis during flight.

PMID- 21903812
TI  - Generation of spatial patterns through cell polarity switching.
AB  - The mechanisms that generate dynamic spatial patterns within proliferating
      tissues are poorly understood, largely because of difficulties in unravelling
      interactions between cell specification, polarity, asymmetric division,
      rearrangements, and growth. We address this problem for stomatal spacing in
      plants, which offer the simplifying advantage that cells do not rearrange. By
      tracking lineages and gene activities over extended periods, we show that limited
      stem cell behavior of stomatal precursors depends on maintenance of the
      SPEECHLESS (SPCH) transcription factor in single daughter cells. Modeling shows
      how this property can lead to observed stereotypical stomata lineages through a
      postmitotic polarity-switching mechanism. The model predicts the location of a
      polarity determinant BASL over multiple divisions, which we validate
      experimentally. Our results highlight the dynamic two-way interactions between
      stem cells and their neighborhood during developmental patterning.

PMID- 21903813
TI  - X-ROS signaling: rapid mechano-chemo transduction in heart.
AB  - We report that in heart cells, physiologic stretch rapidly activates reduced-form
      nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) to produce
      reactive oxygen species (ROS) in a process dependent on microtubules (X-ROS
      signaling). ROS production occurs in the sarcolemmal and t-tubule membranes where
      NOX2 is located and sensitizes nearby ryanodine receptors (RyRs) in the
      sarcoplasmic reticulum (SR). This triggers a burst of Ca(2+) sparks, the
      elementary Ca(2+) release events in heart. Although this stretch-dependent
      "tuning" of RyRs increases Ca(2+) signaling sensitivity in healthy
      cardiomyocytes, in disease it enables Ca(2+) sparks to trigger arrhythmogenic
      Ca(2+) waves. In the mouse model of Duchenne muscular dystrophy, hyperactive X
      ROS signaling contributes to cardiomyopathy through aberrant Ca(2+) release from
      the SR. X-ROS signaling thus provides a mechanistic explanation for the
      mechanotransduction of Ca(2+) release in the heart and offers fresh therapeutic
      possibilities.

PMID- 21903814
TI  - Chromosome organization by a nucleoid-associated protein in live bacteria.
AB  - Bacterial chromosomes are confined in submicrometer-sized nucleoids. Chromosome
      organization is facilitated by nucleoid-associated proteins (NAPs), but the
      mechanisms of action remain elusive. In this work, we used super-resolution
      fluorescence microscopy, in combination with a chromosome-conformation capture
      assay, to study the distributions of major NAPs in live Escherichia coli cells.
      Four NAPs--HU, Fis, IHF, and StpA--were largely scattered throughout the
      nucleoid. In contrast, H-NS, a global transcriptional silencer, formed two
      compact clusters per chromosome, driven by oligomerization of DNA-bound H-NS
      through interactions mediated by the amino-terminal domain of the protein. H-NS
      sequestered the regulated operons into these clusters and juxtaposed numerous DNA
      segments broadly distributed throughout the chromosome. Deleting H-NS led to
      substantial chromosome reorganization. These observations demonstrate that H-NS
      plays a key role in global chromosome organization in bacteria.

PMID- 21903815
TI  - Light-induced structural and functional plasticity in Drosophila larval visual
      system.
AB  - How to build and maintain a reliable yet flexible circuit is a fundamental
      question in neurobiology. The nervous system has the capacity for undergoing
      modifications to adapt to the changing environment while maintaining its
      stability through compensatory mechanisms, such as synaptic homeostasis. Here, we
      describe our findings in the Drosophila larval visual system, where the variation
      of sensory inputs induced substantial structural plasticity in dendritic arbors
      of the postsynaptic neuron and concomitant changes to its physiological output.
      Furthermore, our genetic analyses have identified the cyclic adenosine
      monophosphate (cAMP) pathway and a previously uncharacterized cell surface
      molecule as critical components in regulating experience-dependent modification
      of the postsynaptic dendrite morphology in Drosophila.

PMID- 21903817
TI  - Progress in disaster planning and preparedness since 2001.

PMID- 21903816
TI  - HCN2 ion channels play a central role in inflammatory and neuropathic pain.
AB  - The rate of action potential firing in nociceptors is a major determinant of the
      intensity of pain. Possible modulators of action potential firing include the HCN
      ion channels, which generate an inward current, I(h), after hyperpolarization of
      the membrane. We found that genetic deletion of HCN2 removed the cyclic adenosine
      monophosphate (cAMP)-sensitive component of I(h) and abolished action potential
      firing caused by an elevation of cAMP in nociceptors. Mice in which HCN2 was
      specifically deleted in nociceptors expressing Na(V)1.8 had normal pain
      thresholds, but inflammation did not cause hyperalgesia to heat stimuli. After a
      nerve lesion, these mice showed no neuropathic pain in response to thermal or
      mechanical stimuli. Neuropathic pain is therefore initiated by HCN2-driven action
      potential firing in Na(V)1.8-expressing nociceptors.

PMID- 21903818
TI  - Understanding the mental health effects of indirect exposure to mass trauma
      through the media.

PMID- 21903819
TI  - Health consequences of the World Trade Center disaster: a 10th anniversary
      perspective.

PMID- 21903820
TI  - Molecular characterization of extended-spectrum beta-lactamase-producing Shigella
      isolates from humans in South Africa, 2003-2009.

PMID- 21903821
TI  - Interlaboratory reproducibility of DiversiLab rep-PCR typing and clustering of
      Acinetobacter baumannii isolates.
AB  - We have investigated the reproducibility of DiversiLab rep-PCR fingerprints
      between two laboratories with the aim of determining if the fingerprints and
      clustering are laboratory-specific or portable. One-hundred non-duplicate
      Acinetobacter baumannii isolates were used in this study. DNA isolation and rep
      PCR were each performed separately in two laboratories and rep-PCR patterns
      generated in laboratory A were compared with those from laboratory B. Twelve A.
      baumannii isolates processed in laboratory A showed >=98 % pattern similarity
      with the corresponding 12 isolates tested in laboratory B and were considered
      identical. Sixty-four isolates showed 95-97.9 % similarity with their
      corresponding isolates. Twenty-three isolates showed 90-94 % similarity with the
      corresponding isolates, while one isolate showed only 87.4 % similarity. However,
      intra-laboratory clustering was conserved: isolates that clustered in laboratory
      A also clustered in laboratory B. While clustering was conserved and reproducible
      at two different laboratories, demonstrating the robustness of rep-PCR,
      interlaboratory comparison of individual isolate fingerprints showed more
      variability. This comparison allows conclusions regarding clonality to be reached
      independent of the laboratory where the analysis is performed.

PMID- 21903822
TI  - Serotypes and antibiotic resistance in Group B streptococcus isolated from
      patients at the Maternity Hospital, Kuwait.
AB  - A total of 143 group B streptococcus (GBS) isolates collected from mothers at the
      Maternity Hospital in Kuwait were investigated for their serotypes and antibiotic
      resistance, and screened by PCR for the carriage of genes for resistance to
      tetracycline (tetk, tetM, tetL, tetO), erythromycin (ermA, ermB, ermC, ermTR,
      ermM, mefA, mefE, msrA) and aminoglycosides (aph3, ant4, ant6). All isolates were
      serotyped using a latex agglutination test. Most of the isolates belonged to
      serotypes V (38.5 %), III (20.9 %), Ia (7.7 %) and II (11.2 %). Sixteen isolates
      (11.2 %) were nontypable. All isolates were susceptible to penicillin, ampicillin
      and cefotaxime (MICs 0.016-0.094 ug ml(-1)) but were resistant to trimethoprim
      (92.3 %), tetracycline (89.5 %), minocycline (89.5 %), high-level kanamycin (76.9
      %), chloramphenicol (30.0 %), erythromycin (12.6 %), clindamycin (7.0 %), high
      level streptomycin (3.5 %) and ciprofloxacin (0.7 %). The tetracycline-resistant
      isolates contained tetM (94.5 %), tetO (3.9 %), tetL (1.6 %) and tetK (0.8 %).
      The erythromycin-resistant isolates contained ermB (61.1 %), ermTR (38.9 %), ermA
      (5.5 %), mefA (5.5 %) and mefE (11 %). All high-level kanamycin-resistant
      isolates contained aph3. One of the high-level streptomycin-resistant isolates
      contained ant6. Partial DNA sequencing of aph3 revealed sequences with 99 %
      similarity to aph3 found in Enterococcus faecium, Enterococcus faecalis,
      Staphylococcus aureus and Staphylococcus epidermidis, suggesting that the GBS
      isolates could have acquired aph3 from other Gram-positive cocci. The high
      proportion of isolates with resistance to tetracycline, high-level kanamycin and
      trimethoprim, and the increase in the prevalence of erythromycin resistance,
      represents an emerging public health concern that needs further surveillance.

PMID- 21903823
TI  - Emergence of carbapenem-resistant clinical Enterobacteriaceae isolates from a
      teaching hospital in Shanghai, China.
AB  - Carbapenems such as imipenem and meropenem are first-line agents for the
      treatment of serious nosocomial infections caused by multidrug-resistant clinical
      isolates of bacteria belonging to the family Enterobacteriaceae. However,
      resistance to carbapenems has increased dramatically among members of the family
      Enterobacteriaceae isolated from a teaching hospital in Shanghai, China. In the
      present study, we investigated the prevalence and molecular characteristics of
      carbapenem-resistant clinical isolates of Enterobacteriaceae. None of the 77
      clinical isolates collected from 2002 to 2009 were susceptible to ertapenem and
      only 6.5 % and 1.3 % of isolates were susceptible to imipenem and meropenem,
      respectively. Colistin and tigecycline were found to be the most active agents
      against carbapenem-resistant Enterobacteriaceae isolates, inhibiting 90 % of
      isolates at a concentration of 1 ug ml(-1) and 4 ug ml(-1), respectively. The
      results of PFGE analysis suggested that many of the KPC-2-producing isolates of
      Citrobacter freundii and Klebsiella pneumoniae were clonally related. Most of
      these isolates were isolated from the same ward, namely the neurosurgical ward,
      suggesting horizontal transfer of the KPC-2-encoding gene in these isolates. Of
      the 77 isolates, 84.4 % were found, by PCR, to be capable of carbapenemase
      production. SDS-PAGE analysis revealed that 75.3 % (58/77) of the isolates had
      lost at least one porin protein. Our results suggested that the prompt detection
      of carbapenemase-producing strains is critical for the containment of nosocomial
      transmission. As no novel antimicrobials have been identified for use in the
      treatment of these pan-drug-resistant isolates, further studies should focus on
      the rational use of available antibiotics, the implementation of active
      antibiotic resistance surveillance and the strict implementation of infection
      control measures to avoid the rapid spread or outbreak of carbapenemase-producing
      Enterobacteriaceae in health-care facilities.

PMID- 21903824
TI  - Small-molecule inhibitors of biofilm formation in laboratory and clinical
      isolates of Candida albicans.
AB  - Candida albicans cells have the ability to form biofilms on biotic and abiotic
      surfaces, such as indwelling medical devices. C. albicans cells can interconvert
      between budded and hyphal growth forms, herein termed the budded-to-hyphal
      transition (BHT), which is important for the formation of mature biofilms.
      Previous work identified 23 small organic molecules that could inhibit the BHT
      but did not affect C. albicans cell viability or budded cell growth. These BHT
      inhibitors were proposed to inhibit multiple signalling pathways regulating the
      BHT, many of which also regulate biofilm formation. However, only three of the
      BHT inhibitors, buhytrinA, ETYA and CGP-37157, were capable of inhibiting in
      vitro biofilm formation of wild-type laboratory C. albicans strains. When
      clinical C. albicans isolates were examined for their ability to form biofilms,
      only 11 of the 28 clinical isolates tested (39%) were capable of forming
      biofilms. Although buhytrinA, ETYA and CGP-37157 could inhibit the BHT of all 28
      clinical isolates, they were only able to inhibit biofilm formation of a subset
      of these clinical isolates, with ETYA having 100% efficacy. These data indicate
      that the biofilm-forming capability of laboratory and clinical isolates of C.
      albicans, as well as the efficacy of BHT inhibitors against these different
      isolates, can differ dramatically. These differences between laboratory and
      clinical isolates should be an important aspect to consider when examining
      potentially new antifungal therapeutics.

PMID- 21903825
TI  - Phenotypic and molecular characterization of quinolone resistance in
      Mycobacterium abscessus subsp. bolletii recovered from postsurgical infections.
AB  - Several outbreaks of infections caused by rapidly growing mycobacteria (RGM) were
      reported in many Brazilian states (2032 notified cases) from 2004 to 2010. Most
      of the confirmed cases were mainly associated with Mycobacterium massiliense
      (recently renamed as Mycobacterium abscessus subsp. bolletii) BRA100 clone,
      recovered from patients who had undergone invasive procedures in which medical
      instruments had not been properly sterilized and/or disinfected. Since quinolones
      have been an option for the treatment of general RGM infections and have been
      suggested for therapeutic schemes for these outbreaks, we evaluated the in vitro
      activities of all generations of quinolones for clinical and reference RGM by
      broth microdilution, and analysed the peptide sequences of the quinolone
      resistance determining regions (QRDRs) of GyrA and GyrB after DNA sequencing
      followed by amino acid translation. Fifty-four isolates of M. abscessus subsp.
      bolletii, including clone BRA100, recovered in different states of Brazil, and 19
      reference strains of RGM species were characterized. All 54 M. abscessus subsp.
      bolletii isolates were resistant to all generations of quinolones and showed the
      same amino acids in the QRDRs, including the Ala-83 in GyrA, and Arg-447 and Asp
      464 in GyrB, described as being responsible for an intrinsic low level of
      resistance to quinolones in mycobacteria. However, other RGM species showed
      distinct susceptibilities to this class of antimicrobials and patterns of
      mutations contrary to what has been traditionally defined, suggesting that other
      mechanisms of resistance, different from gyrA or gyrB mutations, may also be
      involved in resistance to high levels of quinolones.

PMID- 21903826
TI  - Comparison of plasmid-mediated quinolone resistance and extended-spectrum beta
      lactamases in third-generation cephalosporin-resistant Enterobacteriaceae from
      four Irish hospitals.
AB  - In this study, the frequency of extended-spectrum beta-lactamases (ESBL) and
      plasmid-mediated quinolone resistance (PMQR) mechanisms were investigated in 206
      clinical isolates of third-generation cephalosporin (3GC)-resistant
      Enterobacteriaceae in four hospitals in the Republic of Ireland. bla(CTX-M-15)
      was the predominant ESBL gene. Of these 3GC resistant isolates, 54 % were also
      resistant to ciprofloxacin. Investigation of the PMQR mechanisms revealed that
      the aac(6')Ib-cr gene predominated in fluoroquinolone-resistant (FQR) strains of
      Escherichia coli and Klebsiella pneumoniae, while the qnrA gene predominated in
      the FQR strains of Enterobacter. The bla(CTX-M-15) gene was frequently identified
      with the aac(6')Ib-cr gene but was not always on the same plasmid. The prevalence
      of the bla(CTX-M-15) gene appeared to be hospital-dependent. The epidemiology of
      both ESBL-producing and PMQR strains within the four hospitals indicated that
      their prevalence is not due to the spread of these resistance genes between
      isolates from different hospitals.

PMID- 21903827
TI  - Emergence of new PCR ribotypes from the hypervirulent Clostridium difficile 027
      lineage.
AB  - Clostridium difficile is the most common cause of antibiotic-associated diarrhoea
      worldwide. Over the past 10 years, the incidence and severity of disease have
      increased in North America and Europe due to the emergence of a hypervirulent
      clone designated PCR ribotype 027. In this study, we sought to identify
      phenotypic differences among a collection of 26 presumed PCR ribotype 027 strains
      from the US and the UK isolated between 1988 and 2008 and also re-evaluated the
      PCR ribotype. We demonstrated that some of the strains typed as BI by restriction
      endonuclease analysis, and presumed to be PCR ribotype 027, were in fact other
      PCR ribotypes such as 176, 198 and 244 due to slight variation in banding pattern
      compared to the 027 strains. The reassigned 176, 198 and 244 ribotype strains
      were isolated in the US between 2001 and 2004 and appeared to have evolved
      recently from the 027 lineage. In addition, the UK strains were more motile and
      more resistant to most of the antibiotics compared to the US counterparts. We
      conclude that there should be a heightened awareness of newly identified PCR
      ribotypes such as 176, 198 and 244, and that they may be as problematic as the
      notorious 027 strains.

PMID- 21903828
TI  - Multilocus differentiation of the related dermatophytes Microsporum canis,
      Microsporum ferrugineum and Microsporum audouinii.
AB  - Microsporum ferrugineum, an uncommon causative agent of dermatophytosis, has
      restricted endemicity. Iranian strains suspected to be M. ferrugineum from two
      patients with tinea were analysed using the rDNA internal transcribed spacer
      (ITS) region and the partial beta-tubulin (BT2) and translation elongation factor
      1-alpha (TEF1) genes. Strains were compared to reference strains to differentiate
      M. ferrugineum from its relatives Microsporum canis and Microsporum audouinii.
      Inter-species differences for TEF1 and BT2 were found to be higher than for the
      ITS region, which is the current molecular standard for species identification in
      dermatophytes. Intra-species variation was zero for each of the markers. In
      silico analysis showed that the restriction enzymes BanI and BshNI were together
      sufficient to differentiate the three species based on TEF1, whereas a two-step
      digestion was needed with BT2 or the ITS region. The prevalence of M. ferrugineum
      in clinical samples in Iran appeared to be higher than suspected on the basis of
      routine phenotypic identification.

PMID- 21903829
TI  - Infection with Helicobacter pylori strains lacking dupA is associated with an
      increased risk of gastric ulcer and gastric cancer development.
AB  - Recently, dupA was reported as a new virulence factor in Helicobacter pylori, but
      its association with gastroduodenal disorders and its mode of action are still
      unclear. Here, an association of the dupA status with different disease groups
      was determined and a biological explanation for the observed associations was
      tested. In total, 216 H. pylori isolates were obtained from 232 presumed H.
      pylori-infected patients. A positive association was observed between the
      occurrence of duodenal ulcer (DU) and the presence of dupA [odds ratio (OR) 24.2;
      95 % confidence interval (CI) 10.6-54.8]. In addition, an inverse association
      between the occurrence of gastric cancer (GC) [OR 0.16; 95 % CI 0.05-0.47] and
      gastric ulcer (GU) [OR 0.34; 95 % CI 0.16-0.68] with the presence of dupA was
      observed. A putative explanation for the observed associations might be a more
      corpus-located infection (pan-gastritis) by the dupA-positive strains due to
      their increased acid resistance. Indeed, a strong association between dupA
      positive H. pylori isolated from gastritis patients and in vitro acid resistance
      was observed (P<0.05). The observed higher acid resistance of the dupA-positive
      strains suggests that these strains are adapted to a stomach with high gastric
      acid output. This may in part explain the observed associations, as an increased
      gastric acid output is thought to be typical for an antrum-predominant H. pylori
      infection and, whilst this is associated with an increased risk of DU formation,
      it also decreases the risk for the genesis of GUs and GC.

PMID- 21903855
TI  - Abdominal aortic aneurysm treatment: minimally invasive fast-track surgery and
      endovascular technique.
AB  - In our department we started a program in order to offer a mini-invasive approach
      to all patients affected by abdominal aortic aneurysms (AAAs), trying to offer
      this option also to patients not eligible for endovascular aneurysm repair (EVAR)
      due to unfavorable anatomy, age under 65 years and aorto-iliac occlusive disease,
      considering nowadays EVAR is the gold-standard for the mini-invasive treatment of
      AAAs. The aim of this study was to compare endovascular versus fast-track
      surgical treatment in patients undergoing elective surgery for AAAs. We wanted to
      verify if it was possible to be totally mini-invasive in the treatment of AAAs. A
      total of 128 patients were chosen for the study. Ninety-four patients were
      enrolled in the OPEN group and 34 were enrolled in the EVAR group. This study
      demonstrates that minimally invasive treatment with the fast-track protocol may
      be a valid alternative to EVAR.

PMID- 21903856
TI  - Statin treatment is associated with reduced toll-like receptor 4
      immunohistochemical expression on carotid atherosclerotic plaques: a novel effect
      of statins.
AB  - Toll-like receptor 4 (TLR4) has been recently implicated in inflammatory pathways
      involved in carotid plaque destabilization. Given that statins have plaque
      stabilization and inflammation reduction effects, we investigated whether TLR4
      expression on carotid atherosclerotic plaques correlates with statin intake.
      Carotid atherosclerotic plaques were obtained on 140 patients (preoperative
      statin intake, n = 70). TLR4 immunohistochemical expression was investigated in
      endothelial cells (ECs), macrophages (MACs) and smooth muscle cells (SMCs) of
      carotid atheroma. TLR4 positivity, over-expression and intensity of
      immunostaining were compared in statin versus no-statin users. The results of
      this study showed that statin users had a significantly lower expression of TLR4
      in ECs (P = 0.02, 0.001, 0.006 for TLR4 positivity, increased intensity and over
      expression, respectively). Similarly, TLR4 positivity was less pronounced in
      carotid plaque MACs of statin users (P = 0.03). No carotid specimen with
      increased EC TLR4 intensity or over-expression was observed among statin users.
      The prevalence of any cerebrovascular accident was 61.4% in the 'no statin'
      versus 18.6% in the 'statin' group (odds ratio for statin use: 0.14, 95% CI: 0.07
      0.31, P < 0.001). In conclusion, statin treatment is associated with attenuated
      TLR4 expression on human carotid atherosclerotic plaques and a reduced risk of
      carotid-related cerebrovascular events. TLR4 may potentially mediate statins'
      plaque stabilization effects. Further investigation is necessary.

PMID- 21903857
TI  - The endovascular management of splenic artery aneurysms and pseudoaneurysms.
AB  - The purpose of this study was to evaluate outcomes of the endovascular treatment
      of splenic artery aneurysms (SAAs) and pseudoaneurysms (SAPAs). From April 2003
      to December 2009, 12 patients (mean age 46.8 years, range 29-58) with SAAs (n =
      9) or SAPAs (n = 3) underwent endovascular treatment. Four patients were
      asymptomatic and three had ruptured aneurysms. Lesions were in the proximal
      splenic artery (n = 3), intermediate splenic artery (n = 3) and distal splenic
      artery (n = 6). Endovascular procedures included embolization by sac packing (n =
      5), sandwich occlusion of the splenic artery (n = 4) or stent graft deployment (n
      = 3). Computed tomography (CT) was done before the operation, 3 and 12 months
      after the operation, then yearly. Endovascular treatment was successful at the
      first attempt in all 12 (100%) patients, with complete angiographic exclusion of
      the aneurysm at the end of the operation. The mean amount of contrast medium used
      was 165 mL (range 100-230), and the mean total procedure time was 92 minutes
      (range 55-160). No major complications occurred. Postoperational CT scans showed
      splenic multisegmental infarcts in eight patients (66.7%, 8/12) and among them
      postembolization syndrome developed in six patients, manifesting as abdominal
      pain and fever. The mean follow-up was 32 months (range 9-51). No patient
      demonstrated gross evidence of aneurysm sac growth, and no significant decrease
      in aneurysm sac size postintervention was noted on follow-up. The endovascular
      management of SAAs and SAPAs is safe and effective and may induce less mortality
      than open surgery. Regardless of the etiology, endovascular treatment can provide
      excellent mid-term results.

PMID- 21903858
TI  - BRAFV600E mutation, TIMP-1 upregulation, and NF-kappaB activation: closing the
      loop on the papillary thyroid cancer trilogy.
AB  - BRAF(V600E) is the most common mutation found in papillary thyroid carcinoma
      (PTC). Tissue inhibitor of metalloproteinases (TIMP-1) and nuclear factor (NF)
      kappaB have been shown to play an important role in thyroid cancer. In
      particular, TIMP-1 binds its receptor CD63 on cell surface membrane and activates
      Akt signaling pathway, which is eventually responsible for its anti-apoptotic
      activity. The aim of our study was to evaluate whether interplay among these
      three factors exists and exerts a functional role in PTCs. To this purpose, 56
      PTC specimens were analyzed for BRAF(V600E) mutation, TIMP-1 expression, and NF
      kappaB activation. We found that BRAF(V600E) mutation occurs selectively in PTC
      nodules and is associated with hyperactivation of NF-kappaB and upregulation of
      both TIMP-1 and its receptor CD63. To assess the functional relationship among
      these factors, we first silenced BRAF gene in BCPAP cells, harboring BRAF(V600E)
      mutation. We found that silencing causes a marked decrease in TIMP-1 expression
      and NF-kappaB binding activity, as well as decreased invasiveness. After
      treatment with specific inhibitors of MAPK pathway, we found that only sorafenib
      was able to increase IkappaB-alpha and reduce both TIMP-1 expression and Akt
      phosphorylation in BCPAP cells, indicating that BRAF(V600E) activates NF-kappaB
      and this pathway is MEK-independent. Taken together, our findings demonstrate
      that BRAF(V600E) causes upregulation of TIMP-1 via NF-kappaB. TIMP-1 binds then
      its surface receptor CD63, leading eventually to Akt activation, which in turn
      confers antiapoptotic behavior and promotion of cell invasion. The recognition of
      this functional trilogy provides insight on how BRAF(V600E) determines cancer
      initiation, progression, and invasiveness in PTC, also identifying new
      therapeutic targets for the treatment of highly aggressive forms.

PMID- 21903860
TI  - The skeleton: a multi-functional complex organ: the role of key signalling
      pathways in osteoclast differentiation and in bone resorption.
AB  - Osteoclasts are the specialised cells that resorb bone matrix and are important
      both for the growth and shaping of bones throughout development as well as during
      the process of bone remodelling that occurs throughout life to maintain a healthy
      skeleton. Osteoclast formation, function and survival are tightly regulated by a
      network of signalling pathways, many of which have been identified through the
      study of rare monogenic diseases, knockout mouse models and animal strains
      carrying naturally occurring mutations in key molecules. In this review, we
      describe the processes of osteoclast formation, activation and function and
      discuss the major transcription factors and signalling pathways (including those
      that control the cytoskeletal rearrangements) that are important at each stage.

PMID- 21903859
TI  - mTOR is a selective effector of the radiation therapy response in androgen
      receptor-positive prostate cancer.
AB  - Ionizing radiation (IR) is used frequently in the management of multiple tumor
      types, including both organ-confined and locally advanced prostate cancer (PCa).
      Enhancing tumor radiosensitivity could both reduce the amount of radiation
      required for definitive treatment and improve clinical outcome. Androgen
      suppression therapy improves clinical outcomes when combined with radiation
      therapy but is associated with significant acute and chronic toxicities; hence,
      there is a clear need for alternative means to increase the therapeutic window of
      radiotherapy. Herein, it is demonstrated that the mammalian target of rapamycin
      (mTOR) inhibitors rapamycin (sirolimus) and temsirolimus limit both hormone
      therapy (HT)-sensitive and castration-resistant PCa (CRPC) cell proliferation as
      single agents and have a profound radiosensitization effect when used in
      combination with IR. Importantly, the observed radiosensitization was influenced
      by the treatment schedule, in which adjuvant administration of mTOR inhibitors
      was most effective in limiting PCa cell population doubling. This schedule
      dependent influence on in vitro treatment outcome was determined to be the result
      of relative effects on the cell cycle kinetics. Finally, adjuvant administration
      of either mTOR inhibitor tested after IR significantly decreased clonogenic cell
      survival of both HT-sensitive and CRPC cells compared with IR alone. Taken
      together, these data demonstrate that inhibition of mTOR confers a
      radiosensitization phenotype that is dependent on relative cell cycle kinetics
      and provide a foundation for clinical assessment.

PMID- 21903861
TI  - AMP-activated protein kinase pathway and bone metabolism.
AB  - There is increasing evidence that osteoporosis, similarly to obesity and
      diabetes, could be another disorder of energy metabolism. AMP-activated protein
      kinase (AMPK) has emerged over the last decade as a key sensing mechanism in the
      regulation of cellular energy homeostasis and is an essential mediator of the
      central and peripheral effects of many hormones on the metabolism of appetite,
      fat and glucose. Novel work demonstrates that the AMPK signaling pathway also
      plays a role in bone physiology. Activation of AMPK promotes bone formation in
      vitro and the deletion of alpha or beta subunit of AMPK decreases bone mass in
      mice. Furthermore, AMPK activity in bone cells is regulated by the same hormones
      that regulate food intake and energy expenditure through AMPK activation in the
      brain and peripheral tissues. AMPK is also activated by antidiabetic drugs such
      as metformin and thiazolidinediones (TZDs), which also impact on skeletal
      metabolism. Interestingly, TZDs have detrimental skeletal side effects, causing
      bone loss and increasing the risk of fractures, although the role of AMPK
      mediation is still unclear. These data are presented in this review that also
      discusses the potential roles of AMPK in bone as well as the possibility for AMPK
      to be a future therapeutic target for intervention in osteoporosis.

PMID- 21903862
TI  - 5alpha-Reduced glucocorticoids: a story of natural selection.
AB  - 5alpha-Reduced glucocorticoids (GCs) are formed when one of the two isozymes of
      5alpha-reductase reduces the Delta(4-5) double bond in the A-ring of GCs. These
      steroids are largely viewed inert, despite the acceptance that other 5alpha
      dihydro steroids, e.g. 5alpha-dihydrotestosterone, retain or have increased
      activity at their cognate receptors. However, recent findings suggest that 5alpha
      reduced metabolites of corticosterone have dissociated actions on GC receptors
      (GRs) in vivo and in vitro and are thus potential candidates for safer anti
      inflammatory steroids. 5alpha-Dihydro- and 5alpha-tetrahydro-corticosterone can
      bind with GRs, but interest in these compounds had been limited, since they only
      weakly activated metabolic gene transcription. However, a greater understanding
      of the signalling mechanisms has revealed that transactivation represents only
      one mode of signalling via the GR and recently the abilities of 5alpha-reduced
      GCs to suppress inflammation have been demonstrated in vitro and in vivo. Thus,
      the balance of parent GC and its 5alpha-reduced metabolite may critically affect
      the profile of GR signalling. 5alpha-Reduction of GCs is up-regulated in liver in
      metabolic disease and may represent a pathway that protects from both GC-induced
      fuel dyshomeostasis and concomitant inflammatory insult. Therefore, 5alpha
      reduced steroids provide hope for drug development, but may also act as
      biomarkers of the inflammatory status of the liver in metabolic disease. With
      these proposals in mind, careful attention must be paid to the possible adverse
      metabolic effects of 5alpha-reductase inhibitors, drugs that are commonly
      administered long term for the treatment of benign prostatic hyperplasia.

PMID- 21903863
TI  - Global Igfbp1 deletion does not affect prostate cancer development in a c-Myc
      transgenic mouse model.
AB  - Circulating insulin-like growth factor binding protein 1 (IGFBP1) levels vary in
      response to nutritional status, and pre-clinical studies suggest that elevated
      IGFBP1 may be protective against the development and progression of prostate
      cancer. We hypothesized that global deletion of Igfbp1 would accelerate the
      development of prostate cancer in a c-Myc transgenic mouse model. To test our
      hypothesis, c-Myc transgenic mice (Myc/BP-1 wild-type (WT)) were crossed and
      interbred with the Igfbp1 knockout mice (Myc/BP-1 KO). The animals were placed on
      a high-protein diet at weaning, weighed every 2 weeks, and euthanized at 16 weeks
      of age. Prostate histopathology was assessed and proliferation status was
      determined by Ki-67 and proliferating cell nuclear antigen analyses. IGF-related
      serum biomarkers and body composition were measured. No significant difference in
      the incidence of prostate cancer was observed between the Myc/BP-1 KO and the
      Myc/BP-1 WT mice (65 and 80% respectively, P=0.48). Proliferation was
      significantly decreased by 71% in prostate tissue of Myc/BP-1 KO mice compared
      with Myc/BP-1 WT mice. Myc/BP-1 KO mice exhibited a significant 6.7% increase in
      body weight relative to the Myc/BP-1 WT mice that was attributed to an increase
      in fat mass. Fasting insulin levels were higher in the Myc/BP-1 KO mice without
      any difference between the groups in fasting glucose concentrations. Thus,
      contrary to our hypothesis, global deletion of Igfbp1 in a c-Myc transgenic mouse
      model did not accelerate the development of prostate cancer. Global Igfbp1
      deletion did result in a significant increase in body weight and body fat mass.
      Further studies are required to understand the underlying mechanisms for these
      metabolic effects.

PMID- 21903864
TI  - The effect of nutrition on the neural mechanisms potentially involved in
      melatonin-stimulated LH secretion in female Mediterranean goats.
AB  - This research examines which neural mechanisms among the endogenous opioid,
      dopaminergic, serotonergic and excitatory amino acid systems are involved in the
      stimulation of LH secretion by melatonin implantation and their modulation by
      nutritional level. Female goats were distributed to two experimental groups that
      received either 1.1 (group H; n=24) or 0.7 (group L; n=24) times their
      nutritional maintenance requirements. Half of each group was implanted with
      melatonin after a long-day period. Plasma LH concentrations were measured twice
      per week. The effects of i.v. injections of naloxone, pimozide, cyproheptadine
      and N-methyl-d,l-aspartate (NMDA) on LH secretion were assessed the day before
      melatonin implantation and again on days 30 and 45. The functioning of all but
      the dopaminergic systems was clearly modified by the level of nutrition,
      melatonin implantation and time elapsed since implantation. Thirty days after
      implantation, naloxone increased LH concentrations irrespective of the level of
      nutrition (P<0.05), similar to NMDA in the melatonin-implanted H goats (HM;
      P<0.01). On day 45, naloxone increased LH concentrations in the HM animals
      (P<0.05), similar to cyproheptadine in both the non-implanted H (HC) and the HM
      animals (P<0.01). Finally, at 45 days, NMDA increased the LH concentration in all
      subgroups (P<0.01). These results provide evidence that the effects of different
      neural systems on LH secretion are modified by nutritional level and melatonin
      implantation. Endogenous opioids seem to be most strongly involved in the
      inhibition of LH secretion on days 30 and 45 after melatonin implantation.
      However, the serotonergic mechanism appears to be most influenced by nutritional
      level.

PMID- 21903866
TI  - Systemic and direct nose-to-brain transport pharmacokinetic model for remoxipride
      after intravenous and intranasal administration.
AB  - Intranasal (IN) administration could be an attractive mode of delivery for drugs
      targeting the central nervous system, potentially providing a high
      bioavailability because of avoidance of a hepatic first-pass effect and rapid
      onset of action. However, controversy remains whether a direct transport route
      from the nasal cavity into the brain exists. Pharmacokinetic modeling is proposed
      to identify the existence of direct nose-to-brain transport in a quantitative
      manner. The selective dopamine-D2 receptor antagonist remoxipride was
      administered at different dosages, in freely moving rats, by the IN and
      intravenous (IV) route. Plasma and brain extracellular fluid (ECF) concentration
      time profiles were obtained and simultaneously analyzed using nonlinear mixed
      effects modeling. Brain ECF/plasma area under the curve ratios were 0.28 and 0.19
      after IN and IV administration, respectively. A multicompartment pharmacokinetic
      model with two absorption compartments (nose-to-systemic and nose-to-brain) was
      found to best describe the observed pharmacokinetic data. Absorption was
      described in terms of bioavailability and rate. Total bioavailability after IN
      administration was 89%, of which 75% was attributed to direct nose-to brain
      transport. Direct nose-to-brain absorption rate was slow, explaining prolonged
      brain ECF exposure after IN compared with IV administration. These studies
      explicitly provide separation and quantitation of systemic and direct nose-to
      brain transport after IN administration of remoxipride in the rat. Describing
      remoxipride pharmacokinetics at the target site (brain ECF) in a semiphysiology
      based manner would allow for better prediction of pharmacodynamic effects.

PMID- 21903865
TI  - IL1alpha and IL4 signalling in human ovarian surface epithelial cells.
AB  - The human ovarian surface epithelium (hOSE) is a mesothelial layer that surrounds
      the ovary and undergoes injury and repair cycles after ovulation-associated
      inflammation. We previously showed that IL4 is a key regulator of progesterone
      bioavailability during post-ovulatory hOSE repair as it differentially up
      regulated 3beta-HSD1 and 3beta-HSD2 mRNA transcripts and total 3beta
      hydroxysteroid dehydrogenase activity whereas it inhibited androgen receptor (AR)
      expression. We now show that the pro-inflammatory effect of IL1alpha on 3beta
      HSD1 expression is mediated by nuclear factor-kappaB (NF-kappaB), whereas its
      anti-inflammatory action on 3beta-HSD2 expression is exerted via p38 mitogen
      activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K) and NF
      kappaB signalling pathways. The anti-inflammatory IL4 effects on 3beta-HSD1 and
      3beta-HSD2 mRNA expression are mediated through STAT6 and PI3K signalling
      networks. IL4 effects on AR and 3beta-HSD2 expression involve the p38 MAPK
      pathway. We also document that IL4 up-regulates lysyl oxidase (LOX) mRNA
      transcripts, a key gene for extracellular matrix (ECM) deposition and inhibits
      IL1alpha-induced expression of cyclooxygenase-2 (COX-2) mRNA, a gene involved in
      breakdown of ECM, showing a further role in post-ovulatory wound healing. We
      conclude that IL1alpha and IL4 actions in the post-ovulatory wound healing of
      hOSE cells are mediated by different signalling transduction pathways. The p38
      MAPK signalling pathway may have possible therapeutic benefit in inflammation
      associated disorders of the ovary, including cancer.

PMID- 21903867
TI  - Tyrosine phosphatase SHP2 regulates the expression of acyl-CoA synthetase ACSL4.
AB  - Acyl-CoA synthetase 4 (ACSL4) is implicated in fatty acid metabolism with marked
      preference for arachidonic acid (AA). ACSL4 plays crucial roles in physiological
      functions such as steroid synthesis and in pathological processes such as
      tumorigenesis. However, factors regulating ACSL4 mRNA and/or protein levels are
      not fully described. Because ACSL4 protein expression requires tyrosine
      phosphatase activity, in this study we aimed to identify the tyrosine phosphatase
      involved in ACSL4 expression. NSC87877, a specific inhibitor of the tyrosine
      phosphatase SHP2, reduced ACSL4 protein levels in ACSL4-rich breast cancer cells
      and steroidogenic cells. Indeed, overexpression of an active form of SHP2
      increased ACSL4 protein levels in MA-10 Leydig steroidogenic cells. SHP2 has to
      be activated through a cAMP-dependent pathway to exert its effect on ACSL4. The
      effects could be specifically attributed to SHP2 because knockdown of the
      phosphatase reduced ACSL4 mRNA and protein levels. Through the action on ACSL4
      protein levels, SHP2 affected AA-CoA production and metabolism and, finally, the
      steroidogenic capacity of MA-10 cells: overexpression (or knockdown) of SHP2 led
      to increased (or decreased) steroid production. We describe for the first time
      the involvement of SHP2 activity in the regulation of the expression of the fatty
      acid-metabolizing enzyme ACSL4.

PMID- 21903868
TI  - A novel bisphosphonate inhibitor of squalene synthase combined with a statin or a
      nitrogenous bisphosphonate in vitro.
AB  - Statins and nitrogenous bisphosphonates (NBP) inhibit 3-hydroxy-3-methylglutaryl
      coenzyme-A reductase (HMGCR) and farnesyl diphosphate synthase (FDPS),
      respectively, leading to depletion of farnesyl diphosphate (FPP) and disruption
      of protein prenylation. Squalene synthase (SQS) utilizes FPP in the first
      committed step from the mevalonate pathway toward cholesterol biosynthesis.
      Herein, we have identified novel bisphosphonates as potent and specific
      inhibitors of SQS, including the tetrasodium salt of 9-biphenyl-4,8-dimethyl-nona
      3,7-dienyl-1,1-bisphosphonic acid (compound 5). Compound 5 reduced cholesterol
      biosynthesis and lead to a substantial intracellular accumulation of FPP without
      reducing cell viability in HepG2 cells. At high concentrations, lovastatin and
      zoledronate impaired protein prenylation and decreased cell viability, which
      limits their potential use for cholesterol depletion. When combined with
      lovastatin, compound 5 prevented lovastatin-induced FPP depletion and impairment
      of protein farnesylation. Compound 5 in combination with the NBP zoledronate
      completely prevented zoledronate-induced impairment of both protein farnesylation
      and geranylgeranylation. Cotreatment of cells with compound 5 and either
      lovastatin or zoledronate was able to significantly prevent the reduction of cell
      viability caused by lovastatin or zoledronate alone. The combination of an SQS
      inhibitor with an HMGCR or FDPS inhibitor provides a rational approach for
      reducing cholesterol synthesis while preventing nonsterol isoprenoid depletion.

PMID- 21903869
TI  - Comparison of image quality and radiation dose between combined automatic tube
      current modulation and fixed tube current technique in CT of abdomen and pelvis.
AB  - BACKGROUND: Tube current is an important determinant of radiation dose and image
      quality in X-ray-based examination. The combined automatic tube current
      modulation technique (ATCM) enables automatic adjustment of the tube current in
      various planes (x-y and z) based on the size and attenuation of the body area
      scanned. PURPOSE: To compare image quality and radiation dose of the ATCM with
      those of a fixed tube current technique (FTC) in CT of the abdomen and pelvis
      performed with a 16-slice multidetector row CT. MATERIAL AND METHODS: We reviewed
      100 patients in whom initial and follow-up CT of the abdomen and pelvis were
      performed with FTC and ATCM. All acquisition parameters were identical in both
      techniques except for tube current. We recorded objective image noise in liver
      parenchyma, subjective image noise and diagnostic acceptability by using a five
      point scale, radiation dose, and body mass index (BMI, kg/m(2)). Data were
      analyzed with parametric and non-parametric statistical tests. RESULTS: There was
      no significant difference in image noise and diagnostic acceptability between two
      techniques. All subjects had acceptable subjective image noise in both
      techniques. The significant reduction in radiation dose (45.25% reduction) was
      noted with combined ATCM (P < 0.001). There was a significant linear statistical
      correlation between BMI and dose reduction (r = -0.78, P < 0.05). CONCLUSION: The
      ATCM for CT of the abdomen and pelvis substantially reduced radiation dose while
      maintaining diagnostic image quality. Patients with lower BMI showed more
      reduction in radiation dose.

PMID- 21903870
TI  - Preliminary study of whole-body diffusion-weighted imaging in detecting pulmonary
      metastatic lesions from clear cell renal cell carcinoma: comparison with CT.
AB  - BACKGROUND: Whole-body diffusion-weighted imaging (DWI) has been widely used in
      detecting malignant metastases, including pulmonary metastases. PURPOSE: To
      evaluate the possible utility of whole-body DWI in detecting pulmonary metastases
      of patients with clear cell renal cell carcinoma (ccRCC) and compare the exact
      differences between MR and CT in detecting pulmonary lesions. MATERIAL AND
      METHODS: Whole-body DWI and chest CT examinations were performed on nine
      consecutive patients (8 men and 1 woman) with histologically confirmed ccRCC and
      possible metastatic lesions before chemotherapy. RESULTS: CT and MR demonstrated
      pulmonary metastases in seven patients and no metastatic lesions in two patients.
      The numbers of pulmonary metastases detected on CT, DWI-only, T1WI-only and DWI
      in combination with T1WI were 83, 35, 34 and 39, respectively. Metastases with a
      diameter above 1.0 cm could all be detected by DWI and a diameter above 0.7 cm
      could all be detected by DWI in combination with T1WI. Significant differences
      were obtained both for correlationship between diameter and detection rates of
      DWI and T1WI by using Spearman rank correlation analysis. CONCLUSION: Although MR
      cannot be considered a replacement for CT in pulmonary metastases from ccRCC,
      whole-body DWI, with the combination of T1 dual echo, might be helpful for the
      evaluation of tumor response to chemotherapy in the follow-up of patients when
      the diameter of the pulmonary metastases is over 1.0 cm.

PMID- 21903871
TI  - The malaria parasite progressively dismantles the host erythrocyte cytoskeleton
      for efficient egress.
AB  - Plasmodium falciparum is an obligate intracellular pathogen responsible for
      worldwide morbidity and mortality. This parasite establishes a parasitophorous
      vacuole within infected red blood cells wherein it differentiates into multiple
      daughter cells that must rupture their host cells to continue another infectious
      cycle. Using atomic force microscopy, we establish that progressive
      macrostructural changes occur to the host cell cytoskeleton during the last 15 h
      of the erythrocytic life cycle. We used a comparative proteomics approach to
      determine changes in the membrane proteome of infected red blood cells during the
      final steps of parasite development that lead to egress. Mass spectrometry-based
      analysis comparing the red blood cell membrane proteome in uninfected red blood
      cells to that of infected red blood cells and postrupture vesicles highlighted
      two temporally distinct events; (Hay, S. I., et al. (2009). A world malaria map:
      Plasmodium falciparum endemicity in 2007. PLoS Med. 6, e1000048) the striking
      loss of cytoskeletal adaptor proteins that are part of the junctional complex,
      including alpha/beta-adducin and tropomyosin, correlating temporally with the
      emergence of large holes in the cytoskeleton seen by AFM as early ~35 h
      postinvasion, and (Maier, A. G., et al. (2008) Exported proteins required for
      virulence and rigidity of Plasmodium falciparum-infected human erythrocytes. Cell
      134, 48-61) large-scale proteolysis of the cytoskeleton during rupture ~48 h
      postinvasion, mediated by host calpain-1. We thus propose a sequential mechanism
      whereby parasites first remove a selected set of cytoskeletal adaptor proteins to
      weaken the host membrane and then use host calpain-1 to dismantle the remaining
      cytoskeleton, leading to red blood cell membrane collapse and parasite release.

PMID- 21903874
TI  - Beyond anti-Muslim sentiment: opposing the Ground Zero mosque as a means to
      pursuing a stronger America.
AB  - Americans' opposition toward building an Islamic community center at Ground Zero
      has been attributed solely to a general anti-Muslim sentiment. We hypothesized
      that some Americans' negative reaction was also due to their motivation to
      symbolically pursue a positive U.S. group identity, which had suffered from a
      concurrent economic and political downturn. Indeed, when participants perceived
      that the United States was suffering from lowered international status, those who
      identified strongly with the country, as evidenced especially by a high respect
      or deference for group symbols, reported a stronger opposition to the "Ground
      Zero mosque" than participants who identified weakly with the country did.
      Furthermore, participants who identified strongly with the country also showed a
      greater preference for buildings that were symbolically congruent than for
      buildings that were symbolically incongruent with the significance of Ground
      Zero, and they represented Ground Zero with a larger symbolic size. These
      findings suggest that identifying group members' underlying motivations provides
      unusual insights for understanding intergroup conflict.

PMID- 21903873
TI  - Airway delivery of soluble factors from plastic-adherent bone marrow cells
      prevents murine asthma.
AB  - Asthma affects an estimated 300 million people worldwide and accounts for 1 of
      250 deaths and 15 million disability-adjusted life years lost annually. Plastic
      adherent bone marrow-derived cell (BMC) administration holds therapeutic promise
      in regenerative medicine. However, given the low cell engraftment in target
      organs, including the lung, cell replacement cannot solely account for the
      reported therapeutic benefits. This suggests that BMCs may act by secreting
      soluble factors. BMCs also possess antiinflammatory and immunomodulatory
      properties and may therefore be beneficial for asthma. Our objective was to
      investigate the therapeutic potential of BMC-secreted factors in murine asthma.
      In a model of acute and chronic asthma, intranasal instillation of BMC
      conditioned medium (CdM) prevented airway hyperresponsiveness (AHR) and
      inflammation. In the chronic asthma model, CdM prevented airway smooth muscle
      thickening and peribronchial inflammation while restoring blunted salbutamol
      induced bronchodilation. CdM reduced lung levels of the T(H)2 inflammatory
      cytokines IL-4 and IL-13 and increased levels of IL-10. CdM up-regulated an IL-10
      induced and IL-10-secreting subset of T regulatory lymphocytes and promoted IL-10
      expression by lung macrophages. Adiponectin (APN), an antiinflammatory adipokine
      found in CdM, prevented AHR, airway smooth muscle thickening, and peribronchial
      inflammation, whereas the effect of CdM in which APN was neutralized or from APN
      knock-out mice was attenuated compared with wild-type CdM. Our study provides
      evidence that BMC-derived soluble factors prevent murine asthma and suggests APN
      as one of the protective factors. Further identification of BMC-derived factors
      may hold promise for novel approaches in the treatment of asthma.

PMID- 21903875
TI  - Cardiac and vascular responses to thigh cuffs and respiratory maneuvers on
      crewmembers of the International Space Station.
AB  - BACKGROUND: The transition to microgravity eliminates the hydrostatic gradients
      in the vascular system. The resulting fluid redistribution commonly manifests as
      facial edema, engorgement of the external neck veins, nasal congestion, and
      headache. This experiment examined the responses to modified Valsalva and Mueller
      maneuvers measured by cardiac and vascular ultrasound (ECHO) in a baseline steady
      state and under the influence of thigh occlusion cuffs available as a
      countermeasure device (Braslet cuffs). METHODS: Nine International Space Station
      crewmember subjects (expeditions 16-20) were examined in 15 experiment sessions
      101 +/- 46 days after launch (mean +/- SD; 33-185). Twenty-seven cardiac and
      vascular parameters were obtained with/without respiratory maneuvers before and
      after tightening of the Braslet cuffs (162 parameter states/session). Quality of
      cardiac and vascular ultrasound examinations was assured through remote
      monitoring and guidance by investigators from the NASA Telescience Center in
      Houston, TX, and the Mission Control Center in Korolyov, Moscow region, Russia.
      RESULTS: 14 of 81 conditions (27 parameters measured at baseline, Valsalva, and
      Mueller maneuver) were significantly different when the Braslet was applied.
      Seven of 27 parameters were found to respond differently to respiratory maneuvers
      depending on the presence or absence of thigh compression. CONCLUSIONS: Acute
      application of Braslet occlusion cuffs causes lower extremity fluid sequestration
      and exerts commensurate measurable effects on cardiac performance in
      microgravity. Ultrasound techniques to measure the hemodynamic effects of thigh
      cuffs in combination with respiratory maneuvers may serve as an effective tool in
      determining the volume status of a cardiac or hemodynamically compromised patient
      at the "microgravity bedside."

PMID- 21903877
TI  - Respiratory muscle training improves hemodynamics, autonomic function,
      baroreceptor sensitivity, and respiratory mechanics in rats with heart failure.
AB  - Respiratory muscle training (RMT) improves functional capacity in chronic heart
      failure (HF) patients, but the basis for this improvement remains unclear. We
      evaluate the effects of RMT on the hemodynamic and autonomic function, arterial
      baroreflex sensitivity (BRS), and respiratory mechanics in rats with HF. Rats
      were assigned to one of four groups: sedentary sham (n = 8), trained sham (n =
      8), sedentary HF (n = 8), or trained HF (n = 8). Trained animals underwent a RMT
      protocol (30 min/day, 5 day/wk, 6 wk of breathing through a resistor), whereas
      sedentary animals did not. In HF rats, RMT had significant effects on several
      parameters. It reduced left ventricular (LV) end-diastolic pressure (P < 0.01),
      increased LV systolic pressure (P < 0.01), and reduced right ventricular
      hypertrophy (P < 0.01) and pulmonary (P < 0.001) and hepatic (P < 0.001)
      congestion. It also decreased resting heart rate (HR; P < 0.05), indicating a
      decrease in the sympathetic and an increase in the vagal modulation of HR. There
      was also an increase in baroreflex gain (P < 0.05). The respiratory system
      resistance was reduced (P < 0.001), which was associated with the reduction in
      tissue resistance after RMT (P < 0.01). The respiratory system and tissue
      elastance (Est) were also reduced by RMT (P < 0.01 and P < 0.05, respectively).
      Additionally, the quasistatic Est was reduced after RMT (P < 0.01). These
      findings show that a 6-wk RMT protocol in HF rats promotes an improvement in
      hemodynamic function, sympathetic and vagal heart modulation, arterial BRS, and
      respiratory mechanics, all of which are benefits associated with improvements in
      cardiopulmonary interaction.

PMID- 21903876
TI  - Characterization of the liver kinase B1-mouse protein-25 -Ste-20-related adaptor
      protein complex in adult mouse skeletal muscle.
AB  - In liver, the AMP-activated protein kinase kinase (AMPKK) complex was identified
      as the association of liver kinase B1 (LKB1), mouse protein 25 (MO25alpha/beta),
      and Ste-20-related adaptor protein (STRADalpha/beta); however, this complex has
      yet to be characterized in skeletal muscle. We demonstrate the expression of the
      LKB1-MO25-STRAD complex in skeletal muscle, confirm the absence of mRNA splice
      variants, and report the relative mRNA expression levels of these proteins in
      control and muscle-specific LKB1 knockout (LKB1(-/-)) mouse muscle. LKB1
      detection in untreated control and LKB1(-/-) muscle lysates revealed two protein
      bands (50 and 60 kDa), although only the heavier band was diminished in LKB1(-/-)
      samples [55 +/- 2.5 and 13 +/- 1.5 arbitrary units (AU) in control and LKB1(-/-),
      respectively, P < 0.01], suggesting that LKB1 is not represented at 50 kDa, as
      previously cited. The 60-kDa LKB1 band was further confirmed following
      purification using polyethylene glycol (43 +/- 5 and 8.4 +/- 4 AU in control and
      LKB1(-/-), respectively, P < 0.01) and ion-exchange fast protein liquid
      chromatography. Mass spectrometry confirmed LKB1 protein detection in the 60-kDa
      protein band, while none was detected in the 50-kDa band. Coimmunoprecipitation
      assays demonstrated LKB1-MO25-STRAD complex formation. Quantitative PCR revealed
      significantly reduced LKB1, MO25alpha, and STRADbeta mRNA in LKB1(-/-) muscle.
      These findings demonstrate that the LKB1-MO25-STRAD complex is the principal
      AMPKK in skeletal muscle.

PMID- 21903878
TI  - Catechins attenuate eccentric exercise-induced inflammation and loss of force
      production in muscle in senescence-accelerated mice.
AB  - Catechins have a great variety of biological actions. We evaluated the potential
      benefits of catechin ingestion on muscle contractile properties, oxidative
      stress, and inflammation following downhill running, which is a typical eccentric
      exercise, in senescence-accelerated prone mice (SAMP). Downhill running (13 m/min
      for 60 min; 16 degrees  decline) induced a greater decrease in the contractile
      force of soleus muscle and in Ca(2+)-ATPase activity in SAMP1 compared with the
      senescence-resistant mice (SAMR1). Moreover, compared with SAMR1, SAMP1 showed
      greater downhill running-induced increases in plasma CPK and LDH activity,
      malondialdehyde, and carbonylated protein as markers of oxidative stress; and in
      protein and mRNA expression levels of the inflammatory mediators such as tumor
      necrosis factor-alpha and monocyte chemoattractant protein-1 in muscle. SAMP1
      exhibited aging-associated vulnerability to oxidative stress and inflammation in
      muscle induced by downhill running. Long-term (8 wk) catechin ingestion
      significantly attenuated the downhill running-induced decrease in muscle force
      and the increased inflammatory mediators in both plasma and gastrocnemius muscle.
      Furthermore, catechins significantly inhibited the increase in oxidative stress
      markers immediately after downhill running, accompanied by an increase in
      glutathione reductase activity. These findings suggest that long-term catechin
      ingestion attenuates the aging-associated loss of force production, oxidative
      stress, and inflammation in muscle after exercise.

PMID- 21903879
TI  - Plasma norepinephrine is an independent predictor of vascular endothelial
      function with aging in healthy women.
AB  - We tested the hypothesis that reductions in vascular endothelial function
      (endothelium-dependent dilation, EDD) with age are related to increases in
      sympathetic activity. Among 314 healthy men and women, age was inversely related
      to brachial artery flow-mediated dilation (FMD) (r = -0.30, P < 0.001), a measure
      of EDD, and positively related to plasma norepinephrine concentrations (PNE), a
      marker of sympathetic activity (r = 0.49, P < 0.001). Brachial FMD was inversely
      related to PNE in all subjects (r = -0.25, P < 0.001) and in men (n = 187, r = 
      0.17, P = 0.02) and women (n = 127, r = -0.37, P < 0.001) separately. After
      controlling for PNE (multiple regression analysis), brachial FMD remained
      significantly related to age in all subjects (r = -0.20, P < 0.001) and in men (r
      = -0.23, P < 0.01), but not women (r = -0.16, P = 0.06). Consistent with this,
      brachial FMD remained significantly related to PNE when controlling for age (r = 
      0.24, P < 0.01) and menopause status (r = -0.24, P < 0.01) in women. Indeed, PNE
      was the strongest independent correlate of brachial FMD in women after
      controlling for conventional cardiovascular disease risk factors (r = -0.22, P =
      0.01). This relation persisted in a subset of women (n = 113) after further
      accounting for the effects of plasma oxidized low-density lipoprotein (P < 0.05),
      a circulating marker of oxidative stress. Endothelium-independent dilation was
      not related to age in either men or women (P > 0.05). These results provide the
      first evidence that EDD is inversely related to sympathetic activity, as assessed
      by PNE, among healthy adults varying in age. In particular, our findings suggest
      that sympathetic nervous system activity may be a key factor involved in the
      modulation of vascular endothelial function with aging in women.

PMID- 21903880
TI  - The role of sympathetic nervous system in the development of neurogenic pulmonary
      edema in spinal cord-injured rats.
AB  - The pronounced activation of sympathetic nervous system is a necessary
      prerequisite for the development of neurogenic pulmonary edema (NPE) in rats with
      balloon compression of spinal cord. In this study we examined whether this is a
      consequence of rapid activation of spinal pathways leading to sympathetic
      venoconstriction, blood pressure rise, and reflex bradycardia. We found that NPE
      development can be prevented by epidural upper thoracic anesthesia or by
      transection of the upper spinal cord. This indicates an important role of spinal
      pathways activation. NPE development can also be prevented by moderate blood
      loss, supporting the role of blood redistribution to pulmonary circulation. In
      rats developing NPE the catecholamine surge following spinal cord compression
      involved not only a dramatic increase of circulating norepinephrine but also of
      epinephrine levels. The pretreatment of rats with alpha-1 adrenoceptor blocker
      prazosin, alpha-2 adrenoceptor blocker yohimbine, or calcium channel blocker
      nifedipine prevented NPE development, whereas the effect of beta-adrenoceptor
      blockade with propranolol was less convincing. In conclusion, considerable
      activation of thoracic spinal pathways, followed by marked catecholamine
      secretion, play a major role in the development of NPE in spinal cord-injured
      rats. Enhanced alpha-adrenergic nifedipine-sensitive vasoconstriction is
      responsible for observed blood pressure changes, subsequent baroreflex
      bradycardia, and blood volume redistribution, which represent major pathogenetic
      mechanisms of NPE development.

PMID- 21903882
TI  - Anandamide modulates carotid sinus nerve afferent activity via TRPV1 receptors
      increasing responses to heat.
AB  - Abnormal respiratory chemosensitivity is implicated in recurrent apnea syndromes,
      with the peripheral chemoreceptors, the carotid bodies, playing a particularly
      important role. Previous work suggests that supraphysiological concentrations of
      the endocannabinoid endovanilloid and TASK channel blocker anandamide (ANA)
      excite carotid bodies, but the mechanism(s) and physiological significance are
      unknown. Given that carotid body output is temperature-sensitive, we hypothesized
      that ANA stimulates carotid body chemosensory afferents via temperature-sensitive
      vanilloid (TRPV1) receptors. To test this hypothesis, we used the dual-perfused
      in situ rat preparation to confirm that independent perfusion of carotid arteries
      with supraphysiological concentrations of ANA strongly excites carotid sinus
      nerve afferents and that this activity is sufficient to increase phrenic
      activity. Next, using ex vivo carotid body preparations, we demonstrate that
      these effects are mediated by TRPV1 receptors, not CB1 receptors or TASK
      channels: in CB1-null mouse preparations, ANA increased afferent activity across
      all levels of Po(2), whereas in TRPV1-null mouse preparations, the stimulatory
      effect of ANA was absent. In rat ex vivo preparations, ANA's stimulatory effects
      were mimicked by olvanil, a nonpungent TRPV1 agonist, and suppressed by the TRPV1
      antagonist AMG-9810. The specific CB1 agonist oleamide had no effect.
      Physiological levels of ANA had no effect alone but increased sensitivity to mild
      hyperthermia. AMG-9810 blocked ANA's effect on the temperature response.
      Immunolabeling and RT-PCR demonstrated that TRPV1 receptors are not expressed in
      carotid body glomus cells but reside in petrosal sensory afferents. Together,
      these results suggest that ANA plays a physiological role in augmenting afferent
      responses to mild hyperthermia by activating TRPV1 receptors on petrosal
      afferents.

PMID- 21903881
TI  - Dose-dependent increases in flow-mediated dilation following acute cocoa
      ingestion in healthy older adults.
AB  - An inverse relation exists between intake of flavonoid-rich foods, such as cocoa,
      and cardiovascular-related mortality. Favorable effects of flavonoids on the
      endothelium may underlie these associations. We performed a randomized, double
      blind, placebo-controlled study to test the hypothesis that acute cocoa ingestion
      dose dependently increases endothelium-dependent vasodilation, as measured by an
      increase in brachial artery flow-mediated dilation (FMD), in healthy older
      adults. Measurements were obtained before (preingestion) and after (1- and 2-h
      postingestion) ingestion of 0 (placebo), 2, 5, 13, and 26 g of cocoa in 23 adults
      (63 +/- 2 yr old, mean +/- SE). Changes in brachial artery FMD 1- and 2-h
      postingestion compared with preingestion were used to determine the effects of
      cocoa. FMD was unchanged 1 (Delta-0.3 +/- 0.2%)- and 2-h (Delta0.1 +/- 0.1%)
      after placebo (0 g cocoa). In contrast, FMD increased both 1-h postingestion (2 g
      cocoa Delta0.0 +/- 0.2%, 5 g cocoa Delta0.8 +/- 0.3%, 13 g cocoa Delta1.0 +/-
      0.3%, and 26 g cocoa Delta1.6 +/- 0.3%: P < 0.05 compared with placebo for 5, 13,
      and 26 g cocoa) and 2-h postingestion (2 g cocoa Delta0.5 +/- 0.3%, 5 g cocoa
      Delta1.0 +/- 0.3%, 13 g cocoa Delta1.4 +/- 0.2%, and 26 g cocoa Delta2.5 +/-
      0.4%: P < 0.05 compared with placebo for 5, 13, and 26 g cocoa) on the other
      study days. A serum marker of cocoa ingestion (total epicatechin) correlated with
      increased FMD 1- and 2-h postingestion (r = 0.44-0.48; both P < 0.05).
      Collectively, these results indicate that acute cocoa ingestion dose dependently
      increases brachial artery FMD in healthy older humans. These responses may help
      to explain associations between flavonoid intake and cardiovascular-related
      mortality in humans.

PMID- 21903883
TI  - An innovative work-loop calorimeter for in vitro measurement of the mechanics and
      energetics of working cardiac trabeculae.
AB  - We describe a unique work-loop calorimeter with which we can measure,
      simultaneously, the rate of heat production and force-length work output of
      isolated cardiac trabeculae. The mechanics of the force-length work-loop
      contraction mimic those of the pressure-volume work-loops experienced by the
      heart. Within the measurement chamber of a flow-through microcalorimeter, a
      trabecula is electrically stimulated to respond, under software control, in one
      of three modes: fixed-end, isometric, or isotonic. In each mode, software
      controls the position of a linear motor, with feedback from muscle force, to
      adjust muscle length in the desired temporal sequence. In the case of a work-loop
      contraction, the software achieves seamless transitions between phases of length
      control (isometric contraction, isometric relaxation, and restoration of resting
      muscle length) and force control (isotonic shortening). The area enclosed by the
      resulting force-length loop represents the work done by the trabecula. The change
      of enthalpy expended by the muscle is given by the sum of the work term and the
      associated amount of evolved heat. With these simultaneous measurements, we
      provide the first estimation of suprabasal, net mechanical efficiency (ratio of
      work to change of enthalpy) of mammalian cardiac trabeculae. The maximum
      efficiency is at the vicinity of 12%.

PMID- 21903884
TI  - Regional variation in the mechanical role of knee meniscus glycosaminoglycans.
AB  - High compressive properties of cartilaginous tissues are commonly attributed to
      the sulfated glycosaminoglycan (GAG) fraction of the extracellular matrix (ECM),
      but this relationship has not been directly measured in the knee meniscus, which
      shows regional variation in GAG content. In this study, biopsies from each
      meniscus region (outer, middle, and inner) were either subjected to
      chondroitinase ABC (CABC) to remove all sulfated GAGs or not. Compressive testing
      revealed that GAG depletion in the inner and middle meniscus regions caused a
      significant decrease in modulus of relaxation (58% and 41% decreases,
      respectively, at 20% strain), and all regions exhibited a significant decrease in
      viscosity (outer: 29%; middle: 58%; inner: 62% decrease). Tensile properties
      following CABC treatment were unaffected for outer and middle meniscus specimens,
      but the inner meniscus displayed significant increases in Young's modulus (41%
      increase) and ultimate tensile stress (40% increase) following GAG depletion.
      These findings suggest that, in the outer meniscus, GAGs contribute to increasing
      tissue viscosity, whereas in the middle and inner meniscus, where GAGs are most
      abundant, these molecules also enhance the tissue's ability to withstand
      compressive loads. GAGs in the inner meniscus also contribute to reducing the
      circumferential tensile properties of the tissue, perhaps due to the pre-stress
      on the collagen network from increased hydration of the ECM. Understanding the
      mechanical role of GAGs in each region of the knee meniscus is important for
      understanding meniscus structure-function relationships and creating design
      criteria for functional meniscus tissue engineering efforts.

PMID- 21903885
TI  - Rapamycin decreases airway remodeling and hyperreactivity in a transgenic model
      of noninflammatory lung disease.
AB  - Airway hyperreactivity (AHR) and remodeling are cardinal features of asthma and
      chronic obstructive pulmonary disease. New therapeutic targets are needed as some
      patients are refractory to current therapies and develop progressive airway
      remodeling and worsening AHR. The mammalian target of rapamycin (mTOR) is a key
      regulator of cellular proliferation and survival. Treatment with the mTOR
      inhibitor rapamycin inhibits inflammation and AHR in allergic asthma models, but
      it is unclear if rapamycin can directly inhibit airway remodeling and AHR, or
      whether its therapeutic effects are entirely mediated through immunosuppression.
      To address this question, we utilized transforming growth factor-alpha (TGF
      alpha) transgenic mice null for the transcription factor early growth response-1
      (Egr-1) (TGF-alpha Tg/Egr-1(ko/ko) mice). These mice develop airway smooth muscle
      thickening and AHR in the absence of altered lung inflammation, as previously
      reported. In this study, TGF-alpha Tg/Egr-1(ko/ko) mice lost body weight and
      developed severe AHR after 3 wk of lung-specific TGF-alpha induction. Rapamycin
      treatment prevented body weight loss, airway wall thickening, abnormal lung
      mechanics, and increases in airway resistance to methacholine after 3 wk of TGF
      alpha induction. Increases in tissue damping and airway elastance were also
      attenuated in transgenic mice treated with rapamycin. TGF-alpha/Egr-1(ko/ko) mice
      on doxycycline for 8 wk developed severe airway remodeling. Immunostaining for
      alpha-smooth muscle actin and morphometric analysis showed that rapamycin
      treatment prevented airway smooth muscle thickening around small airways.
      Pentachrome staining, assessments of lung collagen and fibronectin mRNA levels,
      indicated that rapamycin also attenuated fibrotic pathways induced by TGF-alpha
      expression for 8 wk. Thus rapamycin reduced airway remodeling and AHR,
      demonstrating an important role for mTOR signaling in TGF-alpha-induced/EGF
      receptor-mediated reactive airway disease.

PMID- 21903886
TI  - Increased lipolysis but diminished gene expression of lipases in subcutaneous
      adipose tissue of healthy young males with intrauterine growth retardation.
AB  - Intrauterine growth retardation (IUGR) is associated with a central fat
      distribution and risk of developing type 2 diabetes in adults when exposed to a
      sedentary Western lifestyle. Increased lipolysis is an early defect of metabolism
      in IUGR subjects, but the sites and molecular mechanisms involved are unknown.
      Twenty IUGR and 20 control (CON) subjects, aged 20-30 years, were studied before
      and after 10 days of bed rest using the glucose clamp technique combined with
      measurements of in vivo metabolism by microdialysis technique and blood flow by
      (133)Xe washout technique in subcutaneous abdominal (SCAAT) and femoral (SCFAT)
      adipose tissue. Additionally, mRNA expression of lipases was evaluated in
      biopsies from SCAAT. Lipolysis in SCAAT was substantially higher in IUGR than in
      CON subjects despite markedly lower mRNA expression of lipases. Blood flow was
      higher in IUGR compared with CON in both SCAAT and SCFAT. Whole body insulin
      sensitivity did not differ between groups and decreased after bed rest. After bed
      rest, SCAAT lipolysis remained higher in IUGR compared with CON, and SCFAT
      lipolysis decreased in CON but not in IUGR. Prior to the development of whole
      body insulin resistance, young men with IUGR are characterized by increased in
      vivo adipose tissue lipolysis and blood flow with a paradoxically decreased
      expression of lipases compared with CON, and 10 days of physical inactivity
      underlined the baseline findings. Subjects with IUGR exhibit primary defects in
      adipose tissue metabolism.

PMID- 21903889
TI  - Validating a self-report screen for ADHD in early adulthood using childhood
      parent and teacher ratings.
AB  - OBJECTIVE: This article evaluates the diagnostic utility of a self-report
      screening tool for adults based on Diagnostic and Statistical Manual of Mental
      Disorders (4th ed.; DSM-IV) ADHD criteria. METHOD: Children with speech/language
      (S/L) impairment and typically developing controls had ADHD symptoms rated by
      parents and teachers at ages 5 and 12. At age 19, participants completed the
      Adult Attention Problems Scale (AAPS), an 18-item screen. Receiver operative
      characteristic curve analyses were used to assess the efficiency of this
      instrument in screening for ADHD. RESULTS: The AAPS had moderate sensitivity and
      high specificity, but only for adults without a history of communication
      disorders. CONCLUSION: The AAPS provides clinicians with the only self-report
      scales for ADHD in adulthood, validated with childhood ADHD symptoms assessed by
      multiple raters. However, scale characteristics were poor for the S/L-impaired
      cohort. Given the overlap between language impairment and ADHD, adult ADHD
      measures validated in S/L-impaired samples are needed.

PMID- 21903887
TI  - Exercise lowers estrogen and progesterone levels in premenopausal women at high
      risk of breast cancer.
AB  - Experimental and clinical data support a role for estrogens in the development
      and growth of breast cancer, and lowered estrogen exposure reduces breast cancer
      recurrence and new diagnoses in high-risk women. There is varied evidence that
      increased physical activity is associated with breast cancer risk reduction in
      both pre- and postmenopausal women, perhaps via lowered estrogen levels. The
      purpose of this study was to assess whether exercise intervention in
      premenopausal women at increased breast cancer risk reduces estrogen or
      progesterone levels. Seven healthy premenopausal women at high risk for breast
      cancer completed a seven-menstrual-cycle study. The study began with two
      preintervention cycles of baseline measurement of hormone levels via daily first
      morning urine collection, allowing calculation of average area under the curve
      (AUC) hormone exposure across the menstrual cycle. Participants then began five
      cycles of exercise training to a maintenance level of 300 min per week at 80-85%
      of maximal aerobic capacity. During the last two exercise cycles, urinary
      estradiol and progesterone levels were again measured daily. Total estrogen
      exposure declined by 18.9% and total progesterone exposure by 23.7%. The declines
      were mostly due to decreased luteal phase levels, although menstrual cycle and
      luteal phase lengths were unchanged. The study demonstrated the feasibility of
      daily urine samples and AUC measurement to assess hormone exposure in
      experimental studies of the impact of interventions on ovarian hormones. The
      results suggest value in exercise interventions to reduce hormone levels in high
      risk women with few side effects and the potential for incremental benefits to
      surgical or pharmacologic interventions.

PMID- 21903888
TI  - Swimming training improves the vasodilator effect of angiotensin-(1-7) in the
      aorta of spontaneously hypertensive rat.
AB  - INTRODUCTION: endothelial dysfunction plays a critical role in the pathogenesis
      of hypertension. It is well established that physical training has beneficial
      effects on the cardiovascular system. We recently reported that angiotensin-(1-7)
      [Ang-(1-7)] concentration and the Mas receptor expression is increased in the
      left ventricle of trained spontaneous hypertensive rats (SHR). The vascular
      effects of Ang-(1-7) in trained animals remain so far unknown. In the present
      study we investigated the effects of physical training on the vasodilator effect
      of Ang-(1-7) in the aorta of SHR. METHODOLOGY: normotensive Wistar rats and SHR
      were subjected to an 8-wk period of 5% overload of body weight swimming training.
      Changes in isometric tension were recorded on myograph. Western blot was used to
      investigate Ang-(1-7) receptors expression. RESULTS: in aortas from normotensive
      rats Ang-(1-7) and ACh induced a concentration-dependent vasodilator effect,
      which was not modified by the physical training. Vessels from SHR had an impaired
      vasodilator response to Ang-(1-7) and ACh. The swimming training strongly
      potentiated the vasodilator effect induced by Ang-(1-7) in SHR, but did not
      modify the effect of ACh. Interestingly, Mas receptor protein expression was
      substantially increased by physical training in SHR. In trained SHR, the
      vasodilator effect of Ang-(1-7) was abrogated by removal of the endothelium and
      by the selective Ang-(1-7) receptor antagonists A-779 and d-Pro(7)-Ang-(1-7). l
      NAME decreased Ang-(1-7) vasodilator response and indomethacin abolished the
      remaining dilatory response. CONCLUSION: physical training increased Mas
      receptors expression in SHR aortas, thereby improving the vasodilator effect of
      Ang-(1-7) through an endothelium-dependent mechanism involving nitric oxide and
      prostacyclin.

PMID- 21903890
TI  - Commentaries on viewpoint: control arms in exercise training studies:
      transitioning from an era of intervention efficacy to one of comparative clinical
      effectiveness research.

PMID- 21903891
TI  - Omeprazole impairs the absorption of mycophenolate mofetil but not of enteric
      coated mycophenolate sodium in healthy volunteers.
AB  - In 2 crossover studies, 12 healthy volunteers (6 male/6 female) received a single
      oral dose of mycophenolate mofetil (MMF) 1000 mg or an equimolar dose of enteric
      coated mycophenolate sodium (EC-MPS) 720 mg fasting with and without
      coadministered omeprazole 20 mg bid. The plasma concentrations of mycophenolic
      acid (MPA) and of the inactive metabolite mycophenolic acid glucuronide (MPA-G)
      were measured by high-performance liquid chromatography (HPLC). In addition,
      dissolution of MMF 500 mg or EC-MPS 360 mg tablets was determined using an USP
      paddle apparatus in aqueous buffer of pH 1 to 7. The bioavailability of MPA
      following administration of MMF or EC-MPS was similar except for the time to peak
      concentration, which was longer in the EC-MPS group. Concomitant treatment with
      omeprazole lowered significantly C(max) and AUC(12h) of MPA following
      administration of MMF. The pharmacokinetics of EC-MPS was not affected.
      Dissolution of MMF in aqueous buffer decreased dramatically at pH above 4.5. The
      EC-MPS tablet was stable up to pH 5. Above, EC-MPS was quantitatively
      disintegrated and MPS quantitatively dissolved. There is strong evidence that
      impaired absorption of MMF with concomitant proton pump inhibitors is due to
      incomplete dissolution of MMF in the stomach at elevated pH.

PMID- 21903892
TI  - Aripiprazole associated with acute dystonia, akathisia, and parkinsonism in a
      single patient.

PMID- 21903893
TI  - Investigation of a possible interaction between quetiapine and armodafinil in
      patients with schizophrenia: an open-label, multiple-dose study.
AB  - The wakefulness-promoting medication armodafinil (R-modafinil) is being studied
      as an adjunctive treatment for patients with schizophrenia receiving
      antipsychotic therapy. This open-label study in 37 adults with schizophrenia
      evaluated whether a drug-drug interaction occurs between armodafinil (a moderate
      CYP3A4 inducer) and the atypical antipsychotic quetiapine (primarily metabolized
      by CYP3A4). Patients were required to be on a stable dose of quetiapine >=300 mg
      once daily in the evening before enrollment. Steady-state quetiapine
      pharmacokinetics were determined following daily administration of quetiapine
      alone in the evening (day 5) and then following concomitant armodafinil
      administration (titrated to 250 mg) daily in the morning (day 38). In 25
      evaluable patients, concomitant armodafinil resulted in a statistically
      significant decrease in mean AUC(0-24) and C(max) values of quetiapine by 42% and
      45%, respectively, versus quetiapine alone. Adverse events occurred more
      frequently with combination therapy and were consistent with the known profiles
      of the 2 drugs. No significant changes in mean PANSS negative, positive, and
      total scores or SANS scores were observed. Although the data do not suggest that
      the observed decrease in systemic exposure to quetiapine was associated with a
      change in disease state, patients with schizophrenia should be monitored during
      combination therapy with quetiapine and armodafinil.

PMID- 21903894
TI  - Meclizine metabolism and pharmacokinetics: formulation on its absorption.
AB  - Meclizine, an antihistamine, has been widely used for prophylactic treatment and
      management of motion sickness. However, the onset of action of meclizine was
      about 1 hour for the treatment of motion sickness and vertigo. A new suspension
      formulation of meclizine (MOS) was developed with the intention to achieve a
      rapid effect. To investigate the pharmacokinetics of the new MOS formulation
      versus the marketed meclizine oral tablet (MOT), a phase 1 pharmacokinetic study
      was performed in 20 healthy volunteers. In addition, an in vitro metabolic study
      using human hepatic microsome and recombinant CYP enzyme was also performed to
      determine the metabolic pathway in the human body. The plasma concentration of
      MOS appeared more rapidly in comparison to the MOT. The geometric mean ratios
      (90% confidence interval) of AUC(0-24) and AUC(0-infinity) indicated no
      significant difference in bioavailability between the 2 formulations. CYP2D6 was
      found to be the dominant enzyme for metabolism of meclizine, and its genetic
      polymorphism could contribute to the large interindividual variability. In view
      of the similar bioavailability with a much shorter peak time of the plasma
      meclizine concentration from the MOS formulation, this new formulation is
      expected to produce a much quicker onset of action when used for the management
      of motion sickness.

PMID- 21903896
TI  - Diabetes reduces left ventricular ejection fraction--irrespective of presence and
      extent of coronary artery disease.
AB  - BACKGROUND: It is not clear whether diabetes reduces systolic left ventricular
      function (left ventricular ejection fraction, LVEF) irrespective of coronary
      artery disease (CAD). The aim of this study was to compare the LVEF between
      diabetic and non-diabetic patients with respect to the extent of CAD. METHODS AND
      RESULTS: Consecutive patients undergoing stress myocardial perfusion SPECT (MPS)
      were evaluated. MPS was interpreted using a 20-segment model with a five-point
      scale to define summed stress score (SSS), summed rest score, and summed
      difference score. LVEF was measured by gated SPECT and then compared with respect
      to diabetic status and SSS categories. Of 2635 patients, data of 2400 was
      available. Of these, 24% were diabetic, mean age was 64+/-11y, and 31% were
      female. Diabetics had a significantly lower LVEF compared with non-diabetics
      regardless of the extent of CAD: 53+/-13 and 55+/-13% respectively (P=0.001).
      Diabetics and non-diabetics did not differ significantly in the distribution of
      SSS categories. Diabetes was an independent predictor of decreased LVEF (odds
      ratio 1.6, 95% confidence interval 1.2-2.0; P<0.001). CONCLUSION: Diabetics had a
      lower LVEF than non-diabetics. This difference could be demonstrated regardless
      of CAD extent and might in part explain their generally worse cardiac survival
      compared with non-diabetics on an epidemiological level. In addition, this
      finding points to discussed mechanisms other than CAD lowering LVEF in diabetics.

PMID- 21903895
TI  - Influence of bone remodelling rate on quantitative ultrasound parameters at the
      calcaneus and DXA BMDa of the hip and spine in middle-aged and elderly European
      men: the European Male Ageing Study (EMAS).
AB  - OBJECTIVE: To assess the influence of sex hormones on markers of bone turnover
      and to explore the association between these markers and bone health in middle
      aged and elderly European men. DESIGN: A cross-sectional population-based survey.
      METHODS: Men aged 40-79 years were recruited from population registers in eight
      European centres. Subjects completed a postal questionnaire which included
      questions concerning lifestyle and were invited to undergo quantitative
      ultrasound (QUS) of the calcaneus and to provide a fasting blood sample from
      which the bone markers serum N-terminal propeptide of type 1 procollagen (P1NP)
      and crosslinks (beta C-terminal cross-linked telopeptide (beta-cTX)), total
      testosterone, total oestradiol (E(2)), sex hormone-binding globulin (SHBG) and
      insulin-like growth factor 1 (IGF1) were measured. Dual-energy X-ray
      absorptiometry (DXA) of the hip and lumbar spine was performed in two centres.
      RESULTS: A total of 3120, mean age 59.9 years (s.d.=11.0) were included. After
      adjustment for centre, age, height, weight, lifestyle factors, season and other
      hormones, total and free E(2) were negatively associated with beta-cTX but not
      P1NP while SHBG, IGF1 and parathyroid hormone (PTH) were positively associated
      with both beta-cTX and P1NP. Total or free testosterone was not independently
      associated with either bone marker. After the same adjustments, higher levels of
      both bone markers were significantly associated with lower QUS parameters and
      lower DXA-assessed bone density at the total hip and lumbar spine. CONCLUSIONS:
      E(2), SHBG, IGF1 and PTH contribute significantly to the regulation/rate of bone
      turnover in middle-aged and older European men. Higher rates of bone remodelling
      are negatively associated with male bone health.

PMID- 21903897
TI  - Agrin complicates the niche.

PMID- 21903898
TI  - Zoledronate activates NK cells.

PMID- 21903899
TI  - Gutward, ho! pDCs in SIV infection.

PMID- 21903900
TI  - sIL-2Ralpha + IL-2: fertilizer for tolerance.

PMID- 21903901
TI  - Bcr-Abl adds another twist to cell fate.

PMID- 21903902
TI  - GATA2 finds its macrophage niche.

PMID- 21903903
TI  - Can erythroblasts donate iron?

PMID- 21903905
TI  - Formation in professional education: an examination of the relationship between
      theories of meaning and theories of the self.
AB  - Being formed through learning a practice is best understood within a constitutive
      theory of meaning as articulated by Charles Taylor. Disengaged views of the
      person cannot account for the formative changes in a person's identity and
      capacities upon learning a professional practice. Representational or
      correspondence theories of meaning cannot account for formation. Formation occurs
      over time because students actively seek and take up new concerns and learn new
      knowledge and skills. Engaged situated reasoning about underdetermined practice
      situations requires well-formed skillful clinicians caring for particular
      patients in particular situations.

PMID- 21903906
TI  - Enhancement technologies and the modern self.
AB  - Many people feel uneasy about enhancement technologies, yet have a hard time
      explaining why. This unease is often less with the technologies themselves than
      about the desires and aspirations that they express. I suggest here that we can
      diagnose the source of that unease by looking at three themes that emerge in
      Taylor's writings about the making of the modern self: the importance of social
      recognition, the ethics of authenticity, and the rise of instrumental reason.

PMID- 21903907
TI  - Prognostic importance of early worsening renal function after initiation of
      angiotensin-converting enzyme inhibitor therapy in patients with cardiac
      dysfunction.
AB  - BACKGROUND: Worsening renal function (WRF) in the setting of heart failure has
      been associated with increased mortality. However, it is unclear if this
      decreased survival is a direct result of the reduction in glomerular filtration
      rate (GFR) or if the mechanism underlying the deterioration in GFR is driving
      prognosis. Given that WRF in the setting of angiotensin-converting enzyme
      inhibitor (ACE-I) initiation is likely mechanistically distinct from
      spontaneously occurring WRF, we investigated the relative early WRF-associated
      mortality rates in subjects randomized to ACE-I or placebo. METHODS AND RESULTS:
      Subjects in the Studies Of Left Ventricular Dysfunction (SOLVD) limited data set
      (n=6337) were studied. The interaction between early WRF (decrease in estimated
      GFR >=20% at 14 days), randomization to enalapril, and mortality was the primary
      end point. In the overall population, early WRF was associated with increased
      mortality (adjusted hazard ratio [HR], 1.2; 95% CI, 1.0-1.4; P=0.037). When
      analysis was restricted to the placebo group, this association strengthened
      (adjusted HR, 1.4; 95% CI, 1.1-1.8; P=0.004). However, in the enalapril group,
      early WRF had no adverse prognostic significance (adjusted HR, 1.0; 95% CI, 0.8
      1.3; P=1.0; P=0.09 for the interaction). In patients who continued to receive
      study drug despite early WRF, a survival advantage remained with enalapril
      therapy (adjusted HR, 0.66; 95% CI, 0.5-0.9; P=0.018). CONCLUSIONS: These data
      support the notion that the mechanism underlying WRF is important in determining
      its prognostic significance. Specifically, early WRF in the setting of ACE-I
      initiation appears to represent a benign event that is not associated with a loss
      of benefit from continued ACE-I therapy.

PMID- 21903908
TI  - Anatomic location and somatotopic arrangement of the corticospinal tract at the
      cerebral peduncle in the human brain.
AB  - BACKGROUND AND PURPOSE: Little is known about the detailed anatomic location and
      somatotopic arrangement at the CP. Using DTT with FSL tools, we conducted an
      investigation of the anatomic location and somatotopic arrangement of the CST at
      the CP in the human brain. MATERIALS AND METHODS: We recruited 43 healthy
      volunteers for this study. DTI was obtained by using 1.5T, and CSTs for the hand
      and leg were obtained by using the FSL tool. The somatotopic location of the CST
      was evaluated as the highest probabilistic location at the upper and lower
      midbrain. The posterior boundary was determined as the line between the
      interpeduncular fossa and the lateral sulcus; we then drew a rectangle on the
      basis of the boundary of the CP. RESULTS: In the mediolateral direction, the
      highest probabilistic locations for the hand and leg were an average of 60.46%
      and 69.98% from the medial boundary at the upper midbrain level and 53.44% and
      62.76% at the lower midbrain level, respectively. As for the anteroposterior
      direction, the highest probabilistic locations for the hand and leg were an
      average of 28.26% and 32.03% from the anterior boundary at the upper midbrain
      level and 30.19% and 33.59% at the lower midbrain level, respectively.
      CONCLUSIONS: We found that the hand somatotopy for the CST is located at the
      middle portion of the CP and the leg somatotopy is located lateral to the hand
      somatotopy.

PMID- 21903909
TI  - Image quality and radiation dose of dual-energy CT of the head and neck compared
      with a standard 120-kVp acquisition.
AB  - BACKGROUND AND PURPOSE: DECT offers additional image datasets with potential
      benefits, but its use for H&N imaging is not justified unless image quality is
      preserved without increased radiation dose. The aim of this work was to compare
      image quality and radiation dose between a DE-derived WA image dataset and a
      standard SECT acquisition of the H&N. MATERIALS AND METHODS: Thirty-two patients
      underwent DECT of the H&N (tube voltages 80 and Sn140 kVp) and were compared with
      the last 32 patients who underwent standard SECT (120 kVp) on the same dual
      source scanner. WA images from the 2 DE tubes were compared with images obtained
      with an SE mode. Radiation doses and attenuation measurements of the internal
      jugular vein, submandibular gland, and sternomastoid and tongue muscles were
      compared. Objective image noise was compared at 5 anatomic levels. Two blinded
      readers compared subjective image quality by using 5-point grading scales.
      RESULTS: CTDI(vol) was 12% lower with DE than with SECT, a difference of 1.5 mGy,
      (P < .0001). Objective noise was not significantly different between DE and SECT
      at any of the anatomic levels (P > .05). No significant differences in
      attenuation measurements were observed between DE and SECT (P > .05). No
      significant differences in subjective image quality scores were observed between
      DE and SECT at any of the 5 anatomic levels (P > .05). CONCLUSIONS: DE-derived WA
      images of the H&N are equivalent to standard SE acquisitions and thus can be used
      for routine diagnostic purposes. Multiple additional image datasets can be
      obtained with no radiation dose penalty.

PMID- 21903911
TI  - Unruptured intracranial aneurysms: why clinicians should not resort to
      epidemiologic studies to justify interventions.

PMID- 21903910
TI  - Creation of bifurcation-type elastase-induced aneurysms in rabbits.
AB  - SUMMARY: Elastase incubation was performed in the LCCA in 13 New Zealand white
      rabbits. Three weeks after incubation, DSA demonstrated that 10 (10/13, 77%)
      bifurcation-type aneurysms at the origin of the LCCA were present; mean aneurysm
      neck, width, and height values were 3.7 +/- 1.1, 3.8 +/- 0.9, and 8.7 +/- 2.3 mm,
      respectively. The LCCA can be used to create bifurcation aneurysms in rabbits.

PMID- 21903912
TI  - Thickening and contrast enhancement of spinal roots on MR imaging in Guillain
      Barre syndrome: thoughts on pathologic background.

PMID- 21903913
TI  - Stenting for intracranial aneurysms: how to paint oneself into the proverbial
      corner.

PMID- 21903914
TI  - Risk analysis of unruptured aneurysms using computational fluid dynamics
      technology: preliminary results.
AB  - BACKGROUND AND PURPOSE: The decision as to the treatment of incidental IAs is
      complex. There are no certain quantitative methods that can be used to evaluate
      the risk of rupture in IAs. In recent years, CFD technology has been recognized
      as a potential risk-analysis tool. The aim of this article was to propose a
      hemodynamic parameter, EL, to determine the effects of stable unruptured
      aneurysms and of those that ruptured during the subsequent observation period.
      MATERIALS AND METHODS: Four incidentally found ICA-PcomA aneurysms ruptured
      during the period of observation (ruptured-IAs). Another 26 unruptured aneurysms
      (stable-IAs) with similar location, size, and morphology were compared for the
      differences in hemodynamic factors, such as EL and WSS. RESULTS: The EL
      calculated at the ruptured-IAs was nearly 5 times higher on average than that at
      the stable-IAs (ruptured, 0.00374 +/- 0.0011; stable, 0.000745 +/- 0.0001
      mW/mm(3), P < .001). However, there was no difference between the ruptured and
      stable groups according to the results of time-averaged WSS (P = .8) for ruptured
      and stable-IAs. According to flow visualization, though the mean average inflow
      speed of ruptured-IAs was 2 times higher than that of the stable-IAs, the flow
      inside ruptured-IAs appeared to undergo longer resident tracks, with stronger
      impact on the aneurysm wall. On the contrary, the flow inside stable-IAs passed
      smoothly through the aneurysms. CONCLUSIONS: These preliminary results indicated
      that EL may be a useful parameter for the quantitative estimation of the risks of
      rupture for IAs.

PMID- 21903916
TI  - Sildenafil-induced cervical spinal cord infarction.
AB  - We present a patient with an acute cervical spinal cord infarction resulting from
      the use of sildenafil (Viagra) in combination with his hypertension medication.
      Symptoms were acute and rapidly progressive, and MR imaging with DWI was crucial
      in confirming the diagnosis.

PMID- 21903915
TI  - Interpretation errors in CT angiography of the head and neck and the benefit of
      double reading.
AB  - BACKGROUND AND PURPOSE: CTA provides high-resolution imaging of the head and neck
      vasculature but also of the soft tissues and bones. This results in a large
      volume of information to be interpreted. This study examines interpretation
      errors with head and neck CTAs and assesses whether double reading reduces miss
      rates. MATERIALS AND METHODS: Consecutive CTAs of the neck and intracranial
      circulation were retrospectively identified and reviewed for vascular and
      nonvascular findings by a consensus of 2 neuroradiologists. The results were
      compared with the official report. Significant discrepancies were considered
      those that would have influenced follow-up or management. RESULTS: We reviewed
      503 studies; 144 were originally reported by a staff neuroradiologist alone, 209
      by staff and diagnostic radiology resident, and 150 by staff and neuroradiology
      fellow. Twenty-six significant discrepancies were discovered in 20 studies,
      corresponding to 4.0% of studies with at least 1 miss, and an overall miss rate
      per study of 5.2%. There was at least 1 miss in 6.3% of studies interpreted by a
      staff neuroradiologist alone, 3.3% by staff and resident, and 2.7% by staff and
      fellow. The miss rate differences were not statistically significant. The most
      common misses were small aneurysms (50% of misses). CONCLUSIONS: CTA neck and
      head datasets are now large, and there is a potential for missed findings.
      Significant discrepancies can occur with a low but not insignificant rate.
      Arterial pathology accounted for most discrepancies. This study emphasizes the
      need for careful systematic scrutiny for both vascular and nonvascular pathology
      regardless of indication. Double reading reduces error rates.

PMID- 21903917
TI  - Apparent diffusion coefficient with higher b-value correlates better with viable
      cell count quantified from the cavity of brain abscess.
AB  - BACKGROUND AND PURPOSE: DWI by using higher b-values provides tissue diffusivity
      with less T2 shinethrough effect. VCD in the abscess cavity correlates with ADC
      values. The purpose of this study was to investigate which b-value-derived ADC
      correlates better with VCD. MATERIALS AND METHODS: Thirty patients with brain
      abscess underwent conventional MR imaging and DWI with b = 1000, 2000, and 3000
      s/mm(2) on a 3T MR imaging scanner. ADC values were quantified by placing regions
      of interest inside the abscess cavity in all sections where the lesion was
      apparent on coregistered ADC maps derived from different b-values. VCD was
      measured on pus aspirated. RESULTS: An increase in b-value was associated with a
      decrease in ADC values in normal parenchyma as well as in the abscess cavity. The
      most significant negative correlation of VCD was observed with b = 3000 s/mm(2)
      (r = -0.98, P = .01). CONCLUSIONS: VCD in the abscess cavity can be best assessed
      at b = 3000 s/mm(2) secondary to the reduction in the T2 shinethrough effect. DWI
      with b = 3000 s/mm(2) is of promising value in the assessment of the therapeutic
      response of brain abscess.

PMID- 21903918
TI  - Perineural tumor spread along the sixth cranial nerve: CT and MR imaging.

PMID- 21903919
TI  - Infarction of the corpus callosum: a manifestation of giant cell arteritis.

PMID- 21903920
TI  - The Omega Point and beyond: the singularity event.

PMID- 21903921
TI  - A bat's perspective on navigation.

PMID- 21903922
TI  - Source of the human malaria parasite Plasmodium falciparum.

PMID- 21903923
TI  - The reserve pool of synaptic vesicles acts as a buffer for proteins involved in
      synaptic vesicle recycling.
AB  - Presynaptic nerve terminals contain between several hundred vesicles (for example
      in small CNS synapses) and several tens of thousands (as in neuromuscular
      junctions). Although it has long been assumed that such high numbers of vesicles
      are required to sustain neurotransmission during conditions of high demand, we
      found that activity in vivo requires the recycling of only a few percent of the
      vesicles. However, the maintenance of large amounts of reserve vesicles in many
      evolutionarily distinct species suggests that they are relevant for synaptic
      function. We suggest here that these vesicles constitute buffers for soluble
      accessory proteins involved in vesicle recycling, preventing their loss into the
      axon. Supporting this hypothesis, we found that vesicle clusters contain a large
      variety of proteins needed for vesicle recycling, but without an obvious function
      within the clusters. Disrupting the clusters by application of black widow spider
      venom resulted in the diffusion of numerous soluble proteins into the axons.
      Prolonged stimulation and ionomycin application had a similar effect, suggesting
      that calcium influx causes the unbinding of soluble proteins from vesicles.
      Confirming this hypothesis, we found that isolated synaptic vesicles in vitro
      sequestered soluble proteins from the cytosol in a process that was inhibited by
      calcium addition. We conclude that the reserve vesicles support neurotransmission
      indirectly, ensuring that soluble recycling proteins are delivered upon demand
      during synaptic activity.

PMID- 21903924
TI  - A system for the targeted amplification of bacterial gene clusters multiplies
      antibiotic yield in Streptomyces coelicolor.
AB  - Gene clusters found in bacterial species classified as Streptomyces encode the
      majority of known antibiotics as well as many pharmaceutically active compounds.
      A site-specific recombination system similar to those that mediate plasmid
      conjugation was engineered to catalyze tandem amplification of one of these gene
      clusters in a heterologous Streptomyces species. Three genetic elements were
      known to be required for DNA amplification in S. kanamyceticus: the oriT-like
      recombination sites RsA and RsB, and ZouA, a site-specific relaxase similar to
      TraA proteins that catalyze plasmid transfer. We inserted RsA and RsB sequences
      into the S. coelicolor genome flanking a cluster of 22 genes (act) responsible
      for biosynthesis of the polyketide antibiotic actinorhodin. Recombination between
      RsA and RsB generated zouA-dependent DNA amplification resulting in 4-12 tandem
      copies of the act gene cluster averaging nine repeats per genome. This resulted
      in a 20-fold increase in actinorhodin production compared with the parental
      strain. To determine whether the recombination event required taxon-specific
      genetic effectors or generalized bacterial recombination (recA), it was also
      analyzed in the heterologous host Escherichia coli. zouA was expressed under the
      control of an inducible promoter in wild-type and recA mutant strains. A plasmid
      was constructed with recombination sites RsA and RsB bordering a drug resistance
      marker. Induction of zouA expression generated hybrid RsB/RsA sites, evidence of
      site-specific recombination that occurred independently of recA. ZouA-mediated
      DNA amplification promises to be a valuable tool for increasing the activities of
      commercially important biosynthetic, degradative, and photosynthetic pathways in
      a wide variety of organisms.

PMID- 21903925
TI  - Helicobacter pylori vacuolating cytotoxin A (VacA) engages the mitochondrial
      fission machinery to induce host cell death.
AB  - A number of pathogenic bacteria target mitochondria to modulate the host's
      apoptotic machinery. Studies here revealed that infection with the human gastric
      pathogen Helicobacter pylori disrupts the morphological dynamics of mitochondria
      as a mechanism to induce host cell death. The vacuolating cytotoxin A (VacA) is
      both essential and sufficient for inducing mitochondrial network fragmentation
      through the mitochondrial recruitment and activation of dynamin-related protein 1
      (Drp1), which is a critical regulator of mitochondrial fission within cells.
      Inhibition of Drp1-induced mitochondrial fission within VacA-intoxicated cells
      inhibited the activation of the proapoptotic Bcl-2-associated X (Bax) protein,
      permeabilization of the mitochondrial outer membrane, and cell death. Our data
      reveal a heretofore unrecognized strategy by which a pathogenic microbe engages
      the host's apoptotic machinery.

PMID- 21903926
TI  - Nontelomeric splice variant of telomere repeat-binding factor 2 maintains
      neuronal traits by sequestering repressor element 1-silencing transcription
      factor.
AB  - Telomere repeat-binding factor 2 (TRF2) is critical for telomere integrity in
      dividing stem and somatic cells, but its role in postmitotic neurons is unknown.
      Apart from protecting telomeres, nuclear TRF2 interacts with the master neuronal
      gene-silencer repressor element 1-silencing transcription factor (REST), and
      disruption of this interaction induces neuronal differentiation. Here we report a
      developmental switch from the expression of TRF2 in proliferating neural
      progenitor cells to expression of a unique short nontelomeric isoform of TRF2
      (TRF2-S) as neurons establish a fully differentiated state. Unlike nuclear TRF2,
      which enhances REST-mediated gene repression, TRF2-S is located in the cytoplasm
      where it sequesters REST, thereby maintaining the expression of neuronal genes,
      including those encoding glutamate receptors, cell adhesion, and neurofilament
      proteins. In neurons, TRF2-S-mediated antagonism of REST nuclear activity is
      greatly attenuated by either overexpression of TRF2 or administration of the
      excitatory amino acid kainic acid. Overexpression of TRF2-S rescues kainic acid
      induced REST nuclear accumulation and its gene-silencing effects. Thus, TRF2-S
      acts as part of a unique developmentally regulated molecular switch that plays
      critical roles in the maintenance and plasticity of neurons.

PMID- 21903927
TI  - The next generation of genetic investigations into the Black Death.

PMID- 21903928
TI  - A small pool of vesicles maintains synaptic activity in vivo.
AB  - Chemical synapses contain substantial numbers of neurotransmitter-filled synaptic
      vesicles, ranging from approximately 100 to many thousands. The vesicles fuse
      with the plasma membrane to release neurotransmitter and are subsequently
      reformed and recycled. Stimulation of synapses in vitro generally causes the
      majority of the synaptic vesicles to release neurotransmitter, leading to the
      assumption that synapses contain numerous vesicles to sustain transmission during
      high activity. We tested this assumption by an approach we termed cellular
      ethology, monitoring vesicle function in behaving animals (10 animal models,
      nematodes to mammals). Using FM dye photooxidation, pHluorin imaging, and HRP
      uptake we found that only approximately 1-5% of the vesicles recycled over
      several hours, in both CNS synapses and neuromuscular junctions. These vesicles
      recycle repeatedly, intermixing slowly (over hours) with the reserve vesicles.
      The latter can eventually release when recycling is inhibited in vivo but do not
      seem to participate under normal activity. Vesicle recycling increased only to ~
      5% in animals subjected to an extreme stress situation (frog predation on
      locusts). Synapsin, a molecule binding both vesicles and the cytoskeleton, may be
      a marker for the reserve vesicles: the proportion of vesicles recycling in vivo
      increased to 30% in synapsin-null Drosophila. We conclude that synapses do not
      require numerous reserve vesicles to sustain neurotransmitter release and thus
      may use them for other purposes, examined in the accompanying paper.

PMID- 21903929
TI  - The bacterial actin MreB rotates, and rotation depends on cell-wall assembly.
AB  - Bacterial cells possess multiple cytoskeletal proteins involved in a wide range
      of cellular processes. These cytoskeletal proteins are dynamic, but the driving
      forces and cellular functions of these dynamics remain poorly understood.
      Eukaryotic cytoskeletal dynamics are often driven by motor proteins, but in
      bacteria no motors that drive cytoskeletal motion have been identified to date.
      Here, we quantitatively study the dynamics of the Escherichia coli actin homolog
      MreB, which is essential for the maintenance of rod-like cell shape in bacteria.
      We find that MreB rotates around the long axis of the cell in a persistent
      manner. Whereas previous studies have suggested that MreB dynamics are driven by
      its own polymerization, we show that MreB rotation does not depend on its own
      polymerization but rather requires the assembly of the peptidoglycan cell wall.
      The cell-wall synthesis machinery thus either constitutes a novel type of
      extracellular motor that exerts force on cytoplasmic MreB, or is indirectly
      required for an as-yet-unidentified motor. Biophysical simulations suggest that
      one function of MreB rotation is to ensure a uniform distribution of new
      peptidoglycan insertion sites, a necessary condition to maintain rod shape during
      growth. These findings both broaden the view of cytoskeletal motors and deepen
      our understanding of the physical basis of bacterial morphogenesis.

PMID- 21903930
TI  - Self-enforcing strategies to deter free-riding in the climate change mitigation
      game and other repeated public good games.
AB  - As the Copenhagen Accord indicates, most of the international community agrees
      that global mean temperature should not be allowed to rise more than two degrees
      Celsius above preindustrial levels to avoid unacceptable damages from climate
      change. The scientific evidence distilled in the Fourth Assessment Report of the
      Intergovernmental Panel on Climate Change and recent reports by the US National
      Academies shows that this can only be achieved by vast reductions of greenhouse
      gas emissions. Still, international cooperation on greenhouse gas emissions
      reductions suffers from incentives to free-ride and to renegotiate agreements in
      case of noncompliance, and the same is true for other so-called "public good
      games." Using game theory, we show how one might overcome these problems with a
      simple dynamic strategy of linear compensation when the parameters of the problem
      fulfill some general conditions and players can be considered to be sufficiently
      rational. The proposed strategy redistributes liabilities according to past
      compliance levels in a proportionate and timely way. It can be used to implement
      any given allocation of target contributions, and we prove that it has several
      strong stability properties.

PMID- 21903931
TI  - Acoustic measurement of the Deepwater Horizon Macondo well flow rate.
AB  - On May 31, 2010, a direct acoustic measurement method was used to quantify fluid
      leakage rate from the Deepwater Horizon Macondo well prior to removal of its
      broken riser. This method utilized an acoustic imaging sonar and acoustic Doppler
      sonar operating onboard a remotely operated vehicle for noncontact measurement of
      flow cross-section and velocity from the well's two leak sites. Over 2,500 sonar
      cross-sections and over 85,000 Doppler velocity measurements were recorded during
      the acquisition process. These data were then applied to turbulent jet and plume
      flow models to account for entrained water and calculate a combined hydrocarbon
      flow rate from the two leak sites at seafloor conditions. Based on the chemical
      composition of end-member samples collected from within the well, this bulk
      volumetric rate was then normalized to account for contributions from gases and
      condensates at initial leak source conditions. Results from this investigation
      indicate that on May 31, 2010, the well's oil flow rate was approximately 0.10 +/
      0.017 m(3) s(-1) at seafloor conditions, or approximately 85 +/- 15 kg s(-1)
      (7.4 +/- 1.3 Gg d(-1)), equivalent to approximately 57,000 +/- 9,800 barrels of
      oil per day at surface conditions. End-member chemical composition indicates that
      this oil release rate was accompanied by approximately an additional 24 +/- 4.2
      kg s(-1) (2.1 +/- 0.37 Gg d(-1)) of natural gas (methane through pentanes),
      yielding a total hydrocarbon release rate of 110 +/- 19 kg s(-1) (9.5 +/- 1.6 Gg
      d(-1)).

PMID- 21903932
TI  - Crystal structure of the hybrid state of ribosome in complex with the guanosine
      triphosphatase release factor 3.
AB  - Protein release factor 3 (RF3), a guanosine triphosphatase, binds to ribosome
      after release of the nascent peptide and promotes dissociation of the class I
      release factors during the termination of protein synthesis. Here we present the
      crystal structure of the 70S ribosome with RF3 in the presence of a
      nonhydrolyzable GTP analogue, guanosine 5'-beta,gamma-methylenetriphosphate
      (GDPCP), refined to 3.8 A resolution. The structure shows that the subunits of
      the ribosome are rotated relative to each other compared to the canonical state,
      resulting in a P/E hybrid state for the transfer RNA. The substantial
      conformational rearrangements in the complex are described and suggest how RF3,
      by stabilizing the hybrid state of the ribosome, facilitates the dissociation of
      class I release factors.

PMID- 21903933
TI  - Delivery of siRNA and other macromolecules into skin and cells using a peptide
      enhancer.
AB  - Delivery of macromolecules into cells and tissues such as skin is a major
      challenge. This obstacle poses a particular challenge for the delivery of siRNA
      where cellular and tissue level transport barriers need to be overcome. siRNAs
      are potential therapeutics for various dermatological diseases including
      psoriasis, atopic dermatitis, and cancer; however, their utility is limited by
      their low absorption across the stratum corneum (SC) and into viable cells of
      skin. Here, we address this challenge using a peptide identified by phage display
      termed skin penetrating and cell entering (SPACE) peptide. In vitro studies
      indicated that the SPACE peptide, when conjugated to cargoes such as small
      molecules and proteins, was able to facilitate their penetration across the SC
      into epidermis and dermis. The peptide also exhibited increased penetration into
      various cells including keratinocytes, fibroblasts, and endothelial cells, likely
      through a macropinocytosis pathway. The ability of SPACE peptide to deliver siRNA
      was tested in vivo using two targets, interleukin-10 and GAPDH. Conjugation of
      the peptide to siRNA led to their enhanced absorption into skin and knockdown of
      corresponding protein targets.

PMID- 21903934
TI  - Menthol attenuates respiratory irritation responses to multiple cigarette smoke
      irritants.
AB  - Menthol, the cooling agent in peppermint, is added to almost all commercially
      available cigarettes. Menthol stimulates olfactory sensations, and interacts with
      transient receptor potential melastatin 8 (TRPM8) ion channels in cold-sensitive
      sensory neurons, and transient receptor potential ankyrin 1 (TRPA1), an irritant
      sensing channel. It is highly controversial whether menthol in cigarette smoke
      exerts pharmacological actions affecting smoking behavior. Using plethysmography,
      we investigated the effects of menthol on the respiratory sensory irritation
      response in mice elicited by smoke irritants (acrolein, acetic acid, and
      cyclohexanone). Menthol, at a concentration (16 ppm) lower than in smoke of
      mentholated cigarettes, immediately abolished the irritation response to
      acrolein, an agonist of TRPA1, as did eucalyptol (460 ppm), another TRPM8
      agonist. Menthol's effects were reversed by a TRPM8 antagonist, AMTB. Menthol's
      effects were not specific to acrolein, as menthol also attenuated irritation
      responses to acetic acid, and cyclohexanone, an agonist of the capsaicin
      receptor, TRPV1. Menthol was efficiently absorbed in the respiratory tract,
      reaching local concentrations sufficient for activation of sensory TRP channels.
      These experiments demonstrate that menthol and eucalyptol, through activation of
      TRPM8, act as potent counterirritants against a broad spectrum of smoke
      constituents. Through suppression of respiratory irritation, menthol may
      facilitate smoke inhalation and promote nicotine addiction and smoking-related
      morbidities.

PMID- 21903935
TI  - A liver-specific microRNA binds to a highly conserved RNA sequence of hepatitis B
      virus and negatively regulates viral gene expression and replication.
AB  - Regulated gene expression and progeny production are essential for persistent and
      chronic infection by human pathogens, such as hepatitis B virus (HBV), which
      affects >400 million people worldwide and is a major cause of liver disease. In
      this study, we provide the first direct evidence that a liver-specific microRNA,
      miR-122, binds to a highly conserved HBV pregenomic RNA sequence via base-pairing
      interactions and inhibits HBV gene expression and replication. The miR-122 target
      sequence is located at the coding region of the mRNA for the viral polymerase and
      the 3' untranslated region of the mRNA for the core protein. In cultured cells,
      HBV gene expression and replication reduces with increased expression of miR-122,
      and the expression of miR-122 decreases in the presence of HBV infection and
      replication. Furthermore, analyses of clinical samples demonstrated an inverse
      linear correlation in vivo between the miR-122 level and the viral loads in the
      peripheral blood mononuclear cells of HBV-positive patients. Our results suggest
      that miR-122 may down-regulate HBV replication by binding to the viral target
      sequence, contributing to the persistent/chronic infection of HBV, and that HBV
      induced modulation of miR-122 expression may represent a mechanism to facilitate
      viral pathogenesis.

PMID- 21903936
TI  - Differential protein kinase C isoform regulation and increased constitutive
      activity of acetylcholine-regulated potassium channels in atrial remodeling.
AB  - RATIONALE: Atrial fibrillation (AF) causes atrial-tachycardia remodeling (ATR),
      with enhanced constitutive acetylcholine-regulated K+ current (I(KAChC))
      contributing to action potential duration shortening and AF promotion. The
      underlying mechanisms are unknown. OBJECTIVE: To evaluate the role of protein
      kinase C (PKC) isoforms in ATR-induced I(KAChC) activation. METHODS AND RESULTS:
      Cells from ATR-dogs (400-bpm atrial pacing for 1 week) were compared to control
      dog cells. In vitro tachypaced (TP; 3 Hz) canine atrial cardiomyocytes were
      compared to parallel 1-Hz paced cells. I(KAChC) single-channel activity was
      assessed in cell-attached and cell-free (inside-out) patches. Protein expression
      was assessed by immunoblot. In vitro TP activated I(KAChC), mimicking effects of
      in vivo ATR. Discrepant effects of PKC activation and inhibition between control
      and ATR cells suggested isoform-selective effects and altered PKC isoform
      distribution. Conventional PKC isoforms (cPKC; including PKCalpha) inhibited,
      whereas novel isoforms (including PKCepsilon) enhanced, acetylcholine-regulated
      K+ current (I(KACh)) in inside-out patches. TP and ATR downregulated PKCalpha (by
      33% and 37%, respectively) and caused membrane translocation of PKCepsilon,
      switching PKC predominance to the stimulatory novel isoform. TP increased [Ca2+]i
      at 2 hours by 30%, with return to baseline at 24 hours. Buffering [Ca2+]i during
      TP with the cell-permeable Ca2+ chelator BAPTA-AM (1 MUmol/L) or inhibiting the
      Ca2+-dependent protease calpain with PD150606 (20 MUmol/L) prevented PKCalpha
      downregulation and TP enhancement of I(KAChC). PKCepsilon inhibition with a cell
      permeable peptide inhibitor suppressed TP/ATR-induced I(KAChC) activation,
      whereas cPKC inhibition enhanced I(KAChC) activity in 1-Hz cells. CONCLUSIONS:
      PKC isoforms differentially modulate I(KACh), with conventional Ca(2+)-dependent
      isoforms inhibiting and novel isoforms enhancing activity. ATR causes a rate
      dependent PKC isoform switch, with Ca2+/calpain-dependent downregulation of
      inhibitory PKCalpha and membrane translocation of stimulatory PKCepsilon,
      enhancing I(KAChC). These findings provide novel insights into mechanisms
      underlying I(KAChC) dysregulation in AF.

PMID- 21903938
TI  - MicroRNA-29 in aortic dilation: implications for aneurysm formation.
AB  - RATIONALE: Aging represents a major risk factor for coronary artery disease and
      aortic aneurysm formation. MicroRNAs (miRs) have emerged as key regulators of
      biological processes, but their role in age-associated vascular pathologies is
      unknown. OBJECTIVE: We aim to identify miRs in the vasculature that are regulated
      by age and play a role in age-induced vascular pathologies. METHODS AND RESULTS:
      Expression profiling of aortic tissue of young versus old mice identified several
      age-associated miRs. Among the significantly regulated miRs, the increased
      expression of miR-29 family members was associated with a profound downregulation
      of numerous extracellular matrix (ECM) components in aortas of aged mice,
      suggesting that this miR family contributes to ECM loss, thereby sensitizing the
      aorta for aneurysm formation. Indeed, miR-29 expression was significantly induced
      in 2 experimental models for aortic dilation: angiotensin II-treated aged mice
      and genetically induced aneurysms in Fibulin-4(R/R) mice. More importantly, miR
      29b levels were profoundly increased in biopsies of human thoracic aneurysms,
      obtained from patients with either bicuspid (n=79) or tricuspid aortic valves
      (n=30). Finally, LNA-modified antisense oligonucleotide-mediated silencing of miR
      29 induced ECM expression and inhibited angiotensin II-induced dilation of the
      aorta in mice. CONCLUSION: In conclusion, miR-29-mediated downregulation of ECM
      proteins may sensitize the aorta to the formation of aneurysms in advanced age.
      Inhibition of miR-29 in vivo abrogates aortic dilation in mice, suggesting that
      miR-29 may represent a novel molecular target to augment matrix synthesis and
      maintain vascular wall structural integrity.

PMID- 21903939
TI  - HCN3 contributes to the ventricular action potential waveform in the murine
      heart.
AB  - RATIONALE: The hyperpolarization-activated current I(h) that is generated by
      hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) plays a key
      role in the control of pacemaker activity in sinoatrial node cells of the heart.
      By contrast, it is unclear whether I(h) is also relevant for normal function of
      cardiac ventricles. OBJECTIVE: To study the role of the HCN3-mediated component
      of ventricular I(h) in normal ventricular function. METHODS AND RESULTS: To test
      the hypothesis that HCN3 regulates the ventricular action potential waveform, we
      have generated and analyzed a HCN3-deficient mouse line. At basal heart rate,
      mice deficient for HCN3 displayed a profound increase in the T-wave amplitude in
      telemetric electrocardiographic measurements. Action potential recordings on
      isolated ventricular myocytes indicate that this effect was caused by an
      acceleration of the late repolarization phase in epicardial myocytes.
      Furthermore, the resting membrane potential was shifted to more hyperpolarized
      potentials in HCN3-deficient mice. Cardiomyocytes of HCN3-deficient mice
      displayed approximately 30% reduction of total I(h). At physiological ionic
      conditions, the HCN3-mediated current had a reversal potential of approximately 
      35 mV and displayed ultraslow deactivation kinetics. CONCLUSIONS: We propose that
      HCN3 together with other members of the HCN channel family confer a depolarizing
      background current that regulates ventricular resting potential and counteracts
      the action of hyperpolarizing potassium currents in late repolarization. In
      conclusion, our data indicate that HCN3 plays an important role in shaping the
      cardiac action potential waveform.

PMID- 21903937
TI  - Phosphodiesterase 4D regulates baseline sarcoplasmic reticulum Ca2+ release and
      cardiac contractility, independently of L-type Ca2+ current.
AB  - RATIONALE: Baseline contractility of mouse hearts is modulated in a
      phosphatidylinositol 3-kinase-gamma-dependent manner by type 4 phosphodiesterases
      (PDE4), which regulate cAMP levels within microdomains containing the
      sarcoplasmic reticulum (SR) calcium ATPase type 2a (SERCA2a). OBJECTIVE: The goal
      of this study was to determine whether PDE4D regulates basal cardiac
      contractility. METHODS AND RESULTS: At 10 to 12 weeks of age, baseline cardiac
      contractility in PDE4D-deficient (PDE4D(-/-)) mice was elevated mice in vivo and
      in Langendorff perfused hearts, whereas isolated PDE4D(-/-) cardiomyocytes showed
      increased whole-cell Ca2+ transient amplitudes and SR Ca2+content but unchanged L
      type calcium current, compared with littermate controls (WT). The protein kinase
      A inhibitor R(p)-adenosine-3',5' cyclic monophosphorothioate (R(p)-cAMP) lowered
      whole-cell Ca2+ transient amplitudes and SR Ca2+ content in PDE4D(-/-)
      cardiomyocytes to WT levels. The PDE4 inhibitor rolipram had no effect on cardiac
      contractility, whole-cell Ca2+ transients, or SR Ca2+ content in PDE4D(-/-)
      preparations but increased these parameters in WT myocardium to levels
      indistinguishable from those in PDE4D(-/-). The functional changes in PDE4D(-/-)
      myocardium were associated with increased PLN phosphorylation but not cardiac
      ryanodine receptor phosphorylation. Rolipram increased PLN phosphorylation in WT
      cardiomyocytes to levels indistinguishable from those in PDE4D(-/-)
      cardiomyocytes. In murine and failing human hearts, PDE4D coimmunoprecipitated
      with SERCA2a but not with cardiac ryanodine receptor. CONCLUSIONS: PDE4D
      regulates basal cAMP levels in SR microdomains containing SERCA2a-PLN, but not L
      type Ca2+ channels or ryanodine receptor. Because whole-cell Ca2+ transient
      amplitudes are reduced in failing human myocardium, these observations may have
      therapeutic implications for patients with heart failure.

PMID- 21903940
TI  - Reduced vascular nitric oxide-cGMP signaling contributes to adipose tissue
      inflammation during high-fat feeding.
AB  - OBJECTIVE: Obesity is characterized by chronic inflammation of adipose tissue,
      which contributes to insulin resistance and diabetes. Although nitric oxide (NO)
      signaling has antiinflammatory effects in the vasculature, whether reduced NO
      contributes to adipose tissue inflammation is unknown. We sought to determine
      whether (1) obesity induced by high-fat (HF) diet reduces endothelial nitric
      oxide signaling in adipose tissue, (2) reduced endothelial nitric oxide synthase
      (eNOS) signaling is sufficient to induce adipose tissue inflammation independent
      of diet, and (3) increased cGMP signaling can block adipose tissue inflammation
      induced by HF feeding. METHODS AND RESULTS: Relative to mice fed a low-fat diet,
      an HF diet markedly reduced phospho-eNOS and phospho-vasodilator-stimulated
      phosphoprotein (phospho-VASP), markers of vascular NO signaling. Expression of
      proinflammatory cytokines was increased in adipose tissue of eNOS-/- mice.
      Conversely, enhancement of signaling downstream of NO by phosphodiesterase-5
      inhibition using sildenafil attenuated HF-induced proinflammatory cytokine
      expression and the recruitment of macrophages into adipose tissue. Finally, we
      implicate a role for VASP, a downstream mediator of NO-cGMP signaling in
      mediating eNOS-induced antiinflammatory effects because VASP-/- mice
      recapitulated the proinflammatory phenotype displayed by eNOS-/- mice.
      CONCLUSIONS: These results imply a physiological role for endothelial NO to limit
      obesity-associated inflammation in adipose tissue and hence identify the NO-cGMP
      VASP pathway as a potential therapeutic target in the treatment of diabetes.

PMID- 21903941
TI  - Selective inhibition of matrix metalloproteinase-13 increases collagen content of
      established mouse atherosclerosis.
AB  - OBJECTIVE: Evidence has linked collagen loss with the onset of acute coronary
      events. This study tested the hypothesis that selective matrix metalloproteinase
      13 (MMP-13) collagenase inhibition increases collagen content in already
      established and nascent mouse atheromas. METHODS AND RESULTS: In vitro and in
      situ experiments documented the selectivity and efficacy of an orally available
      MMP-13 inhibitor (MMP13i-A). In vivo observations monitored macrophage
      accumulation and MMP-13 activity using molecular imaging. After 10 weeks of
      MMP13i-A treatment, apolipoprotein E-deficient mice with evolving or established
      lesions exhibited reduced MMP-13 activity without affecting macrophage content,
      measured either by intravital microscopy or fluorescence reflectance imaging.
      Histological analysis indicated that MMP13-iA did not affect plaque size or
      macrophage or smooth muscle cell accumulation. Administration of MMP13i-A to mice
      with evolving or established atheromas substantially increased plaque
      interstitial collagen content in the intima and locally in the fibrous cap,
      compared with vehicle-treated controls. Analysis of collagen revealed thicker
      collagen fibers within the plaques of treated groups. CONCLUSION: Pharmacological
      MMP-13 inhibition yields collagen accumulation in plaques (a feature associated
      in humans with resistance to rupture), even in established plaques. This study,
      of considerable clinical relevance, furnishes new mechanistic insight into
      regulation of the plaque's extracellular matrix and validates molecular imaging
      for studying plaque biology.

PMID- 21903942
TI  - Protein phosphatase 2A promotes endothelial survival via stabilization of
      translational inhibitor 4E-BP1 following exposure to tumor necrosis factor-alpha.
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNFalpha) may change from a stimulator of
      reversible activation of endothelial cells (ECs) to a killer when combined with
      cycloheximide (CHX). The means by which endothelial cells are destined to either
      the survival pathway or the apoptotic pathway are not fully understood. We
      investigated the role of p38 mitogen-activated protein kinase (MAPK) and protein
      phosphatase 2A (PP2A) activation and their regulation of 4E-BP1 stability in ECs
      to determine whether this pathway contributes to apoptosis induced by TNFalpha
      and CHX. METHODS AND RESULTS: Apoptosis was induced in human umbilical vein ECs
      (HUVECs) by treating them with a combination of TNFalpha and CHX (TNFalpha/CHX).
      Activation of p38 MAPK was increased in HUVECs undergoing apoptosis, which was
      associated with degradation of eukaryotic initiation factor 4A regulator 4E-BP1
      in a p38 MAPK-dependent manner. CHX attenuated a TNFalpha-stimulated increase in
      the expression and activity of PP2A. Silencing PP2A expression with small
      interfering RNA transfection mimicked CHX sensitization, increasing HUVEC
      apoptosis with TNFalpha stimulation and suggesting a protective role for PP2A in
      the apoptotic process. CONCLUSION: Our data suggest that (1) TNFalpha stimulates
      PP2A and HUVECs elude apoptosis by PP2A-dependent dephosphorylation of p38 MAPK,
      and (2) CHX-induced inhibition of PP2A leads to maintenance of p38 activity and
      degradation of 4E-BP1, resulting in enhanced TNFalpha-induced apoptosis.

PMID- 21903943
TI  - Genetic variation in liver X receptor alpha and risk of ischemic vascular disease
      in the general population.
AB  - OBJECTIVE: Although animal studies indicate that liver X receptor alpha
      (LXRalpha) might influence risk of atherosclerosis, data in humans remain scarce.
      We tested the hypothesis that genetic variation in LXRalpha associates with risk
      of ischemic vascular disease and/or plasma lipid and lipoprotein levels in the
      general population. METHODS AND RESULTS: We studied 10,281 white persons of
      Danish ancestry from a general population cohort, including 1,986 in whom
      ischemic heart disease (IHD) developed, and 989 in whom ischemic cerebrovascular
      disease developed. We examined another 51,429 white persons of Danish ancestry
      from a general population study, including 3,789 with IHD. We genotyped 10
      genetic variants identified by resequencing LXRalpha. Homozygosity for -840AA/
      115AA(=2.7%) predicted hazard ratios of 1.3 (95% confidence interval, 1.0-1.7)
      for IHD, 1.6 (1.2-2.2) for myocardial infarction, and 1.7 (1.3-2.4) for ischemic
      cerebrovascular disease. The corresponding odds ratios in the second cohort were
      1.1 (0.9-1.4) for IHD and 1.5 (1.1-2.0) for myocardial infarction. In the
      combined studies, odds ratios were 1.2 (1.0-1.4) for IHD and 1.5 (1.2-1.9) for
      myocardial infarction. Homozygosity for -840AA/-115AA did not associate with
      lipid or lipoprotein levels. LXRalpha -1830T>C (tagging the haplotype -1830C/
      840A/-115A, all r(2)>=0.97) associated with 91% increased transcriptional
      activity. CONCLUSIONS: This study suggests that functional genetic variation in
      LXRalpha predicts risk of ischemic vascular disease in the general population.

PMID- 21903944
TI  - Role for circulating osteogenic precursor cells in aortic valvular disease.
AB  - OBJECTIVE: Approximately 13% of aortic valves removed from patients with end
      stage aortic valve disease contain heterotopic ossification (HO). Recently, we
      identified a novel population of circulating osteogenic precursor (COP) cells
      that are derived from bone marrow and have the capability to form bone. These
      cells are identified by coexpression of the osteogenic marker type 1 collagen or
      osteoclacin and the hematopoietic marker CD45. We tested the hypothesis that
      these cells may contribute to heart valve stenosis. METHODS AND RESULTS:
      Quantification of CD45(+) osteoclacin(+) COP cells by flow cytometry showed that
      they represent up to 1.1% of mononuclear cells. Clonally derived COP cells
      produce bone morphogenetic proteins 2 and 4 by immunohistochemical analysis. We
      reviewed 105 cases of end-stage aortic valvular disease and confirmed HO in 13
      archived specimens. Using immunohistochemistry, we identified COP cells by
      coexpression of CD45 and type 1 collagen. There was a statistically significant
      association between the presence of COP cells and early HO lesions. COP cells
      were negligible in regions of unaffected valve leaflets (no HO) from the same
      individuals. CONCLUSIONS: This study provides the first evidence that osteogenic
      cells in the blood home to sites of vascular injury and are associated with HO
      formation in heart valves.

PMID- 21903946
TI  - Plasma lipidomic analysis of stable and unstable coronary artery disease.
AB  - OBJECTIVE: Traditional risk factors for coronary artery disease (CAD) fail to
      adequately distinguish patients who have atherosclerotic plaques susceptible to
      instability from those who have more benign forms. Using plasma lipid profiling,
      this study aimed to provide insight into disease pathogenesis and evaluate the
      potential of lipid profiles to assess risk of future plaque instability. METHODS
      AND RESULTS: Plasma lipid profiles containing 305 lipids were measured on 220
      individuals (matched healthy controls, n=80; stable angina, n=60; unstable
      coronary syndrome, n=80) using electrospray-ionisation tandem mass spectrometry.
      ReliefF feature selection coupled with an L2-regularized logistic regression
      based classifier was used to create multivariate classification models which were
      verified via 3-fold cross-validation (1000 repeats). Models incorporating both
      lipids and traditional risk factors provided improved classification of unstable
      CAD from stable CAD (C-statistic=0.875, 95% CI 0.874-0.877) compared with models
      containing only traditional risk factors (C-statistic=0.796, 95% CI 0.795-0.798).
      Many of the lipids identified as discriminatory for unstable CAD displayed an
      association with disease acuity (severity), suggesting that they are antecedents
      to the onset of acute coronary syndrome. CONCLUSION: Plasma lipid profiling may
      contribute to a new approach to risk stratification for unstable CAD.

PMID- 21903945
TI  - Nucleotide-binding oligomerization domain protein 2 deficiency enhances
      neointimal formation in response to vascular injury.
AB  - OBJECTIVE: Nucleotide-binding oligomerization domain protein 2 (NOD2) stimulates
      diverse inflammatory responses resulting in differential cellular phenotypes. To
      identify the role of NOD2 in vascular arterial obstructive diseases, we
      investigated the expression and pathophysiological role of NOD2 in a vascular
      injury model of neointimal hyperplasia. METHODS AND RESULTS: We first analyzed
      for neointimal hyperplasia following femoral artery injury in NOD2(+/+) and NOD2(
      /-) mice. NOD2(-/-) mice showed a 2.86-fold increase in neointimal formation that
      was mainly composed of smooth muscle (SM) alpha-actin positive cells. NOD2 was
      expressed in vascular smooth muscle cells (VSMCs) and NOD2(-/-) VSMCs showed
      increased cell proliferation in response to mitogenic stimuli, platelet-derived
      growth factor-BB (PDGF-BB), or fetal bovine serum, compared with NOD2(+/+) VSMCs.
      Furthermore, NOD2 deficiency markedly promoted VSMCs migration in response to
      PDGF-BB, and this increased cell migration was attenuated by a
      phosphatidylinositol 3-kinase inhibitor. However, protein kinase C and c-Jun N
      terminal kinase inhibitors exerted negligible effects. Moreover, muramyl
      dipeptide-stimulated NOD2 prevented PDGF-BB-induced VSMCs migration. CONCLUSION:
      Functional NOD2 was found to be expressed in VSMCs, and NOD2 deficiency promoted
      VSMCs proliferation, migration, and neointimal formation after vascular injury.
      These results provide evidence for the involvement of NOD2 in vascular
      homeostasis and tissue injury, serving as a potential molecular target in the
      modulation of arteriosclerotic vascular disease.

PMID- 21903948
TI  - Antithrombotic therapy use at discharge and 1 year in patients with atrial
      fibrillation and acute stroke: results from the AVAIL Registry.
AB  - BACKGROUND AND PURPOSE: Current American Heart Association/American Stroke
      Association guidelines identify warfarin use as a class IA indication in patients
      with atrial fibrillation (AF) and ischemic stroke (IS) or transient ischemic
      attack (TIA). However, few studies have examined factors associated with long
      term antithrombotic therapy use in IS/TIA patients with AF. METHODS: We utilized
      the Get With The Guidelines-Stroke national quality improvement registry and the
      Adherence eValuation After Ischemic Stroke Longitudinal (AVAIL) Registry to
      examine patterns of antithrombotic use at discharge and at 12 months in IS/TIA
      patients with AF. A multivariate logistic regression model was developed to
      identify predictors of warfarin use in this patient population at 12 months.
      RESULTS: Of the 2460 IS/TIA patients, 291 (11.8%) had AF, of which 5.5% of
      patients were discharged on aspirin alone, 49.1% on warfarin alone, 1.4% on
      clopidogrel alone, 34.7% on warfarin plus aspirin, 2.1% on aspirin plus
      clopidogrel, and 1.0% on aspirin plus clopidogrel plus warfarin. Paradoxically,
      there was a decrease in the rate of warfarin use in patients with a CHADS2
      score>3. The only factor associated with warfarin use at 12-month follow-up was
      male gender (adjusted odds ratio, 2.27; confidence interval, 1.22-4.35; P=0.01).
      CONCLUSIONS: Overall, the use of warfarin therapy is high at discharge in IS/TIA
      patients with AF; however, there was a decrease in the rate of warfarin use in
      patients with a CHADS2 score>3. Compared to women, men were more likely to be on
      warfarin at 1 year after the index stroke event. Therefore, opportunities exist
      to improve antithrombotic use in all IS/TIA patients with AF.

PMID- 21903947
TI  - Genome-wide microarray analyses identify the protein C receptor as a novel
      calcineurin/nuclear factor of activated T cells-dependent gene in vascular smooth
      muscle cell phenotypic modulation.
AB  - OBJECTIVE: Calcineurin (Cn) and the nuclear factor of activated T cells (NFAT)
      family of transcription factors are critical in vascular smooth muscle cell (SMC)
      development and pathology. Here, we used a genomics approach to identify and
      validate NFAT gene targets activated during platelet-derived growth factor-BB
      (PDGF-BB)-induced SMC phenotypic modulation. METHODS AND RESULTS: Genome-wide
      expression arrays were used to identify genes both (1) differentially activated
      in response to PDGF-BB and (2) whose differential expression was reduced by both
      the Cn inhibitor cyclosporin A and the NFAT inhibitor A-285222. The 20 most
      pharmacologically sensitive genes were validated by quantitative reverse
      transcription-polymerase chain reaction analysis of PDGF-BB-stimulated SMCs in
      the presence of Cn/NFAT inhibitors, including the VIVIT peptide. In all
      experiments, protein C receptor (PROCR) gene activation was reduced. We showed
      that PROCR expression was virtually absent in untreated, quiescent SMCs. PDGF-BB
      stimulation, however, induced significant PROCR promoter activation and
      downstream protein expression in a Cn/NFAT-dependent manner. Mutation of a
      species-conserved, NFAT binding motif significantly attenuated PDGF-BB-induced
      PROCR promoter activity, thereby distinguishing NFAT as the first PROCR
      transcriptional activator to date. Moreover, SMC PROCR expression was upregulated
      in the neointima as early as 7 days following acute vascular injury in rat
      carotid arteries. CONCLUSION: We hereby report PROCR as a novel, NFAT-dependent
      gene that may be implicated in vascular restenosis and consequent inward
      remodeling.

PMID- 21903949
TI  - Outcomes in mild or rapidly improving stroke not treated with intravenous
      recombinant tissue-type plasminogen activator: findings from Get With The
      Guidelines-Stroke.
AB  - BACKGROUND AND PURPOSE: Mild or rapidly improving stroke is a frequently cited
      reason for not giving intravenous recombinant tissue-type plasminogen activator
      (rtPA), but some of these patients may have poor outcomes. We used data from a
      large nationwide study (Get With The Guidelines-Stroke) to determine risk factors
      for poor outcomes after mild or improving stroke at hospital discharge. METHODS:
      Between 2003 and 2009, there were 29,200 ischemic stroke patients (from 1092
      hospitals) arriving within 2 hours after symptom onset with mild or rapidly
      improving stroke symptoms as the only contraindication to rtPA. Logistic
      regression was used to determine the independent predictors of discharge to home.
      RESULTS: Among 93,517 patients arriving within 2 hours, 31.2% (29,200) did not
      receive rtPA solely because of mild/improving stroke. Among the 29,200
      mild/improving cases, 28.3% were not discharged to home, and 28.5% were unable to
      ambulate without assistance at hospital discharge. The likelihood of home
      discharge was strongly related to initial National Institutes of Health Stroke
      Scale score (P<0.001). In multivariable-adjusted analysis, patients not
      discharged to home were more likely to be older, female, and black; have a higher
      National Institutes of Health Stroke Scale score and vascular risk factors; and
      were less likely to be taking lipid-lowering medication before admission.
      CONCLUSIONS: In this large, nationwide study, a sizeable minority of patients who
      did not receive intravenous rtPA solely because of mild/improving stroke had poor
      short-term outcomes, raising the possibility that stroke-related disability is
      relatively common, even in "mild" stroke. A controlled trial of reperfusion
      therapy in this population may be warranted.

PMID- 21903950
TI  - Fish consumption and the risk of stroke: a dose-response meta-analysis.
AB  - BACKGROUND AND PURPOSE: Fish consumption has been postulated to reduce the risk
      of stroke. We conducted a dose-response meta-analysis to summarize the evidence
      from prospective studies regarding the association between fish consumption and
      stroke risk. METHODS: Pertinent studies were identified by searching Embase and
      PubMed through May 2011 and by reviewing the references of retrieved articles. We
      included prospective studies that reported relative risks with 95% CIs of stroke
      for >=3 categories of fish consumption. Results were combined using a random
      effects model. RESULTS: Fifteen prospective studies, with 9360 stroke events
      among 383 838 participants, were included. An increment of 3 servings/week in
      fish consumption was associated with a 6% reduction in risk of total stroke
      (relative risk, 0.94; 95% CI, 0.89-0.99) without heterogeneity among studies
      (P=0.15, I2=25.7%). Among 9 studies with results for stroke subtypes, the
      relative risks were 0.90 (95% CI, 0.84-0.97) for ischemic stroke and 0.90 (95%
      CI, 0.76-1.06) for hemorrhagic stroke. CONCLUSIONS: These findings indicate that
      fish consumption is weakly inversely associated with the risk of stroke.

PMID- 21903951
TI  - Impact of extracranial-intracranial bypass on cerebrovascular reactivity and
      clinical outcome in patients with symptomatic moyamoya vasculopathy.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to evaluate in symptomatic
      moyamoya patients the effect of surgical revascularization on impaired
      cerebrovascular reactivity (CVR) and its relationship to clinical outcome.
      METHODS: Brain revascularization was performed using a direct superficial
      temporal artery to middle cerebral artery bypass or indirect encephalo-dural
      arterial synangiosis. CVR was measured pre- and 3 months postoperatively using
      blood oxygen level-dependent MRI during iso-oxic hypercapnic changes in end-tidal
      carbon dioxide. Outcomes were assessed by MRI, clinical examination, and modified
      Rankin Scale scores. RESULTS: Fifty-five hemispheres were revascularized in 39
      patients (superficial temporal artery to middle cerebral artery in 47, encephalo
      dural-arterial synangiosis in 8). Surgery reversed CVR impairment in 52
      hemispheres (94.5%) and in 36 of 39 patients (92.3%; Fisher exact test, P<0.001),
      and this was predictive of a patent extracranial-intracranial bypass. New,
      clinically silent perioperative hemorrhages, cortical foci of ischemia, or new
      white matter T2 hyperintensities were detected after 11 surgeries (20%), but no
      new lesions arose after 3 postoperative months. One patient had a clinical
      perioperative stroke (1.8%). In clinical follow-up, 37 of 39 patients (95%) had
      stable or improved modified Rankin Scale scores and 2 patients (5.1%) worsened.
      No patients with patent bypasses or CVR improvements exhibited new clinical
      symptoms, but failure of CVR improvement corresponded to a poorer long-term
      outcome (Fisher exact test, P<0.001). CONCLUSIONS: Cerebral revascularization
      surgery is a safe and effective treatment for reversing preoperative CVR defects
      and may prevent recurrence of preoperative symptoms. Moreover, CVR measurements
      may be useful in long-term follow-up and for predicting bypass patency.

PMID- 21903952
TI  - Longitudinal magnetic resonance imaging of sildenafil treatment of embolic stroke
      in aged rats.
AB  - BACKGROUND AND PURPOSE: Sildenafil provides restorative therapeutic benefits in
      the treatment of experimental stroke. The majority of experimental studies on
      treatment of stroke have been performed in young animals; however, stroke is
      primarily a disease of the aged. Thus, using MRI, we evaluated the effects of
      sildenafil treatment of embolic stroke in aged animals. METHODS: Aged male Wistar
      rats (18 months) were subjected to embolic stroke and treated daily with saline
      (n=10) or with sildenafil (n=10) initiated at 24 hours and subsequently for 7
      days after onset of ischemia. MRI measurements were performed at 24 hours and
      weekly to 6 weeks after embolization. RESULTS: MRI and histological measurements
      demonstrated that sildenafil treatment of aged rats significantly enhanced
      angiogenesis and axonal remodeling after stroke compared to saline-treated aged
      rats. Local cerebral blood flow in the angiogenic area was elevated and expansion
      of the ipsilateral ventricle and, consequently, brain atrophy was significantly
      reduced in the sildenafil-treated rats. CONCLUSIONS: Treatment of embolic stroke
      in aged rats with sildenafil significantly augments angiogenesis and axonal
      remodeling, which increased local blood flow and reduced expansion of the
      ipsilateral ventricle 6 weeks after stroke compared to control aged rats. MRI can
      be used to investigate brain repair after stroke in aged rats.

PMID- 21903953
TI  - Chronic heart failure and ischemic stroke.
AB  - Chronic heart failure (CHF) is one of the leading causes of hospitalization,
      morbidity, and mortality worldwide. This review summarizes current knowledge with
      regard to CHF as a risk factor for ischemic stroke. CHF is associated with an
      increased risk of thrombus formation and is accompanied by a 2- to 3-fold
      increased risk of stroke. Moreover, stroke in CHF patients is associated with
      poor outcome and higher mortality. Available evidence for additional "vascular"
      stroke risk factors in heart failure patients is inconsistent and is mostly
      derived from cohort studies or retrospective analyses. Current guidelines
      recommend anticoagulation for CHF patients with concomitant atrial fibrillation
      but not for those in sinus rhythm. Prospective studies are needed to test whether
      early detection and optimal treatment of CHF reduces the burden of stroke
      associated neurologic and neuropsychological sequelae.

PMID- 21903954
TI  - Letter by Cheong regarding article, "Association between stroke and patients with
      pelvic inflammatory disease: a nationwide population-based study in Taiwan".

PMID- 21903955
TI  - Transient cognitive impairment in TIA and minor stroke.
AB  - BACKGROUND AND PURPOSE: Acute cognitive impairment and delirium occur after major
      stroke and are associated with poor cognitive outcome. We conducted a population
      based study to determine whether transient cognitive impairment (TCI) is seen
      acutely after cerebral transient ischemic attack (TIA) or minor stroke, and
      whether it predicts long-term cognitive decline. METHODS: Mini-mental-state
      examination was performed in consecutive testable patients with TIA or minor
      stroke (National Institutes of Health Stroke Scale <=3) seen acutely (1-7 days)
      in the Oxford Vascular Study (2002-2005) versus after 7 days, and in referrals
      seen acutely who had a subsequent noncerebrovascular diagnosis. We defined TCI as
      a baseline Mini-mental-state examination score >=2 points below the 1-month
      follow-up score, and identified cognitive impairment (Montreal Cognitive
      Assessment [MoCA] <26/30) and severe dementia at 1-, 2-, and 5-year follow-up.
      RESULTS: In 280 TIA and minor stroke patients (mean age/SD 73.5/11.8 years), TCI
      was more frequent in those seen at 1 to 7 days (80/206; 38.9%) versus later
      (14/74; 19%; P=0.002) or in noncerebrovascular patients (10/47; 21%; P=0.004).
      TCI was associated with acute confusion (OR, 5.5; 95% CI, 2.5-11.7; P<0.0001),
      acute infarct on computed tomography (OR, 2.0; 1.2-3.5; P=0.01), and with
      residual focal deficits (OR,1.94; 1.13-3.34; P=0.01). However, it was still seen
      acutely in those whose focal deficits had resolved by time of assessment (41/120;
      34%). Although patients with TCI had similar Mini-mental-state examination score
      by 1 month compared with those without TCI, their 5-year risks of cognitive
      impairment (OR, 4.3; 1.2-15.7; P=0.03) and severe dementia (OR, 4.9; 1.0-25.8;
      P=0.05) were increased. CONCLUSIONS: TCI is a manifestation of TIA and minor
      stroke, and may persist beyond resolution of focal symptoms. Our findings have
      implications for definitions in TIA and minor stroke and suggest that cognitive
      fragility may be revealed by minor cerebrovascular events.

PMID- 21903956
TI  - Emergency department shift change is associated with pneumonia in patients with
      acute ischemic stroke.
AB  - BACKGROUND AND PURPOSE: Emergency department (ED) nurses play a pivotal role in
      early acute ischemic stroke patient management. We hypothesized that patients
      exposed to ED nursing shift changes (SC) may develop pneumonia (PNA) more
      frequently and have worse early outcomes than do patients who have continuity of
      care until stroke unit admission. METHODS: Consecutive acute ischemic stroke
      patients presenting to our ED were studied using chart review and prospectively
      collected registry data. We evaluated the association of patient presence during
      an ED SC (ie, 07:00-08:00, 19:00-20:00) with length of stay in the ED, PNA rates,
      and early outcome measures (discharge disposition, modified Rankin Scale score,
      and death). RESULTS: Three hundred sixty-six consecutive acute ischemic stroke
      patients met the criteria. Of those, 54.9% were present during an SC. After
      adjusting for baseline National Institutes of Health Stroke Scale, admission
      glucose, and intravenous tissue-type plasminogen activator, patients present
      during SC were half as likely to be discharged home or to inpatient rehab (OR,
      0.50; 95% CI, 0.26-0.96; P=0.04) and were 2.5 times more likely to develop PNA
      (OR, 2.54; 95% CI, 1.02-6.30; P=0.045). After additional adjustment for time in
      the ED, the difference in favorable discharge disposition was no longer
      significant, but SC was associated with 5 times the odds of PNA (OR, 5.35; 95%
      CI, 1.34-21.39; P=0.018) compared with patients with continuity of care.
      CONCLUSIONS: In our center, acute ischemic stroke patients present during an ED
      nursing SC experienced higher rates of PNA and had decreased rates of favorable
      discharge disposition compared with patients with continuity of care. Strategies
      to prevent PNA and improve hand-off communication during SC may reduce this risk.

PMID- 21903957
TI  - Isoflavone soy protein supplementation and atherosclerosis progression in healthy
      postmenopausal women: a randomized controlled trial.
AB  - BACKGROUND AND PURPOSE: Although epidemiological and experimental studies suggest
      that dietary intake of soy may be cardioprotective, use of isoflavone soy protein
      (ISP) supplementation as a primary preventive therapy remains unexplored. We
      determined whether ISP reduces subclinical atherosclerosis assessed as carotid
      artery intima-media thickness progression. METHODS: In a double-blind, placebo
      controlled trial, 350 postmenopausal women 45 to 92 years of age without diabetes
      and cardiovascular disease were randomized to 2 evenly divided daily doses of 25
      g soy protein containing 91 mg aglycon isoflavone equivalents or placebo for 2.7
      years. RESULTS: Overall, mean (95% CI) carotid artery intima-media thickness
      progression rate was 4.77 (3.39-6.16) MUm/year in the ISP group and 5.68 (4.30
      7.06) MUm/year in the placebo group. Although carotid artery intima-media
      thickness progression was reduced on average by 16% in the ISP group relative to
      the placebo group, this treatment effect was not statistically significant
      (P=0.36). Among the subgroup of women who were randomized within 5 years of
      menopause, ISP participants had on average a 68% lower carotid artery intima
      media thickness progression rate than placebo participants 2.16 (-1.10 to 5.43)
      versus 6.79 (3.56-10.01) MUm/year (P=0.05). ISP supplementation had a null effect
      on women who were >5 years beyond menopause when randomized. There were no major
      adverse events from ISP supplementation. CONCLUSIONS: ISP supplementation did not
      significantly reduce subclinical atherosclerosis progression in postmenopausal
      women. Subgroup analysis suggests that ISP supplementation may reduce subclinical
      atherosclerosis in healthy young (median age, 53 years) women at low-risk for
      cardiovascular disease who were <5 years postmenopausal. These first trial
      results of their kind warrant further investigation.

PMID- 21903958
TI  - Mild stroke and rapidly improving symptoms: it's not always a happy ending.

PMID- 21903959
TI  - Letter by Lee regarding article, "Matrix metalloproteinase-9 in an exploratory
      trial of intravenous minocycline for acute stroke".

PMID- 21903960
TI  - Letter by Knight et al regarding article, "Validation of in vivo magnetic
      resonance imaging blood-brain barrier permeability measurements by comparison
      with gold standard histology".

PMID- 21903961
TI  - Lung cancer and incidence of stroke: a population-based cohort study.
AB  - BACKGROUND AND PURPOSE: Stroke is a known cerebrovascular complication in lung
      cancer patients; however, whether lung cancer patients are at elevated risk of
      developing stroke relative to the noncancer population remains unclear. METHODS:
      The present study used population-based claims data from the Taiwan National
      Health Insurance, which identified 52,089 patients with an initial diagnosis of
      lung cancer between 1999 and 2007, and 104,178 matched noncancer subjects from
      all insured subjects age 20 years and older. Subsequent occurrence of stroke was
      measured until 2008, and the association between lung cancer and the hazard of
      developing stroke was estimated using Cox proportional hazard models. RESULTS:
      The incidence of stroke was 1.5 times higher (25.9 versus 17.4 per 1000 person
      years) in the lung cancer group compared with the comparison group. The
      multivariate-adjusted hazard ratio (HR) comparing lung cancer patients with the
      noncancer group was 1.47 (95% CI, 1.39-1.56) for stroke, 1.78 (95% CI, 1.54-2.05)
      for hemorrhagic stroke, and 1.43 (95% CI, 1.34-1.51) for ischemic stroke. The
      risk of stroke fell over time, decreasing after 1 year of follow-up for men and
      after 2 years of follow-up for women. Within the first year of follow-up, the
      risk of stroke peaked during the first 3 months for men and within 4 to 6 months
      for women. CONCLUSIONS: Lung cancer is associated with increased risk of
      subsequent stroke within 1 year after diagnosis for men and 2 years after
      diagnosis for women.

PMID- 21903962
TI  - Therapeutic modulation of cerebral microhemorrhage in a mouse model of cerebral
      amyloid angiopathy.
AB  - BACKGROUND AND PURPOSE: The aging brain demonstrates frequent MRI and
      pathological evidence of cerebral microbleeds, which are often associated with
      cerebral amyloid angiopathy. To develop new therapeutic strategies for this
      disorder, we studied cerebral microhemorrhage in a well-characterized mouse model
      of cerebral amyloid angiopathy. METHODS: Tg2576 mice were studied at ages ranging
      from 2 to 21 months. Spontaneous and induced microscopic bleeding was analyzed
      with and without a passive anti-amyloid immunization regimen and dietary
      supplementation of ischemic stroke prevention medication dipyridamole. RESULTS:
      Areas of microhemorrhage were easily demonstrated and were significantly more
      prominent in the oldest mice and in animals treated with anti-amyloid
      immunotherapy. Dipyridamole supplementation in the diet generated plasma levels
      >790 ng/mL within the range seen clinically. Dipyridamole treatment did not
      worsen frequency and size of cerebral microscopic bleeding. CONCLUSIONS: The
      Tg2576 mouse is a useful model to study progression and modification of
      spontaneous and immunotherapy-induced cerebral microhemorrhage. Absence of
      microhemorrhage worsening with dipyridamole treatment suggests a potential
      therapeutic role of this agent when ischemic and microhemorrhagic lesions
      coexist.

PMID- 21903963
TI  - Neuroprotection by freezing ischemic penumbra evolution without cerebral blood
      flow augmentation with a postsynaptic density-95 protein inhibitor.
AB  - BACKGROUND AND PURPOSE: The purpose of this study was to determine whether
      neuroprotection is feasible without cerebral blood flow augmentation in
      experimental permanent middle cerebral artery occlusion. METHODS: Rats were
      subjected to permanent middle cerebral artery occlusion by the suture occlusion
      method and were treated 1 hour thereafter with a single 5-minute intravenous
      infusion of the postsynaptic density-95 protein inhibitor Tat-NR2B9c (7.5 mg/kg)
      or saline (n=8/group). Arterial spin-labeled perfusion-weighted MRI and diffusion
      weighted MRI were obtained with a 4.7-T Bruker system at 30, 45, 70, 90, 120,
      150, and 180 minutes postmiddle cerebral artery occlusion to determine cerebral
      blood flow and apparent diffusion coefficient maps, respectively. At 24 hours,
      animals were neurologically scored (0 to 5), euthanized, and the brains stained
      with 2-3-5-triphenyl tetrazolium chloride to ascertain infarct volumes corrected
      for edema. Additionally, the effects of Tat-NR2B9c on adenosine 5'-triphosphate
      levels were measured in vitro in neurons subjected to oxygen-glucose deprivation.
      RESULTS: Final infarct volume was decreased by 30.3% in the Tat-NR2B9c-treated
      animals compared with controls (P=0.028). There was a significant improvement in
      24 hours neurological scores in the Tat-NR2B9c group compared with controls,
      1.8+/-0.5 and 2.8+/-1.0, respectively (P=0.021). Relative to controls, Tat-NR2B9c
      significantly attenuated diffusion-weighted imaging lesion growth and preserved
      the diffusion-weighted imaging/perfusion-weighted imaging mismatch (ischemic
      penumbra) without affecting cerebral blood flow in the ischemic core or penumbra.
      Tat-NR2B9c treatment of primary neuronal cultures resulted in 26% increase in
      cell viability and 34% greater adenosine 5'-triphosphate levels after oxygen
      glucose deprivation. CONCLUSIONS: Preservation of adenosine 5'-triphosphate
      levels in vitro and neuroprotection in permanent middle cerebral artery occlusion
      in rats is achievable without cerebral blood flow augmentation using a
      postsynaptic density-95 protein inhibitor.

PMID- 21903964
TI  - Short-term effect of atorvastatin on carotid artery elasticity: a pilot study.
AB  - BACKGROUND AND PURPOSE: Few studies have examined the early effects of statins on
      carotid artery elasticity, a potential surrogate marker of cardiovascular risk.
      This study examined the short-term effects of atorvastatin 80 mg daily on carotid
      elasticity measured by high-resolution B-mode ultrasound. METHODS: The study
      included 40 stroke-free and statin-naive subjects older than age 45 (mean age,
      70+/-7 years; 55% men; 64% Caribbean-Hispanic). Outcome measures included carotid
      stiffness indices at 14 and 30 days after initiation of treatment. The systolic
      and diastolic diameters of the right common carotid artery were averaged from
      multiple B-mode imaging frames. Absolute and relative changes of strain
      [(systolic diameter-diastolic diameter)/diastolic diameter], stiffness (beta) [ln
      (systolic/diastolic blood pressure)/strain], and distensibility (1/beta adjusted
      for wall thickness) from baseline were compared by the repeated measures t test
      and were considered significant at alpha=0.05. RESULTS: Baseline mean stiffness
      was 0.08 (95% confidence interval [CI], 0.06-0.10). It significantly decreased at
      day 30 to 0.05 (CI, 0.04-0.06; P<0.01). Mean baseline distensibility was 15.25
      (CI, 13.18-17.32), increasing significantly at day 30 to 17.23 (CI, 14.01-20.45;
      P<0.05). An improvement in distensibility of >=10% from baseline was observed in
      29 (73%) subjects. Changes in stiffness and distensibility were maximal among
      subjects with baseline low-density lipoprotein levels<130 mg/dL. CONCLUSIONS:
      Short-term treatment with high-dose atorvastatin was associated with improvement
      in the carotid elasticity metrics. Carotid artery elasticity measured by B-mode
      ultrasound is a simple noninvasive measure of arterial wall function and may be a
      useful surrogate end point in clinical trials targeting individuals at increased
      risk for atherosclerosis.

PMID- 21903965
TI  - Prediction of malignant middle cerebral artery infarction using computed
      tomography-based intracranial volume reserve measurements.
AB  - BACKGROUND AND PURPOSE: Early decompressive surgery in patients with malignant
      middle cerebral artery (MCA) infarction improves outcome. Elevation of
      intracranial pressure depends on both the space occupying brain edema and the
      intracranial volume reserve (cerebrospinal fluid [CSF]). However, CSF volume was
      not investigated as a predictor of malignant infarction so far. We hypothesize
      that assessment of CSF volume in addition to admission infarct size improves
      early prediction of malignant MCA infarction. METHODS: Stroke patients with
      carotid-T or MCA main stem occlusion and ischemic lesion (reduced cerebral blood
      volume [CBV]) on perfusion CT were considered for the analysis. The end point
      malignant MCA infarction was defined by clinical signs of herniation. Volumes of
      CSF and CBV lesion were determined on admission. Receiver-operator
      characteristics analysis was used to calculate predictive values for radiological
      and clinical measurements. RESULTS: Of 52 patients included, 26 (50%) developed
      malignant MCA infarction. Age, a decreased level of consciousness on admission,
      CBV lesion volume, CSF volume, and the ratio of CBV lesion volume to CSF volume
      were significantly different between malignant and nonmalignant groups. The best
      predictor of a malignant course was the ratio of CBV lesion volume to CSF volume
      with a cut-off value of 0.92 (96.2% sensitivity, 96.2% specificity, 96.2%
      positive predictive value, and 96.2% negative predictive value). CONCLUSIONS:
      Based on admission native CT and perfusion CT measurements, the ratio of ischemic
      lesion volume to CSF volume predicts the development of malignant MCA infarction
      with higher accuracy than other known predictors, including ischemic lesion
      volume or clinical characteristics.

PMID- 21903966
TI  - Assessment of the genetic effects of polymorphisms in the osteoprotegerin gene,
      TNFRSF11B, on serum osteoprotegerin levels and carotid plaque vulnerability.
AB  - BACKGROUND AND PURPOSE: Osteoprotegerin (OPG) is a secretory glycoprotein which
      belongs to the tumor necrosis factor receptor family. Various mechanisms have
      been suggested by which calcification might alter atherosclerotic plaque
      stability, but the significance of this intimal calcification is controversial.
      High concentrations of OPG have been associated with the presence of vascular and
      cardiovascular diseases. This study was designed to assess the association
      between gene polymorphisms of the OPG gene (TNFRSF11B), the serum OPG level, and
      plaque stability in patients with carotid atherosclerosis. METHODS: We studied
      177 patients with internal carotid artery stenosis who underwent carotid
      endarterectomy and also 303 controls. Carotid endarterectomy samples removed from
      patients were assessed by immunohistochemistry. Concentrations of OPG were
      measured and gene polymorphisms were examined by polymerase chain reaction and
      restriction enzyme analysis and were compared, initially between patients with
      carotid atherosclerosis and controls, and subsequently between stable and
      unstable carotid plaques. RESULTS: We found that the GG genotype of the T245G
      polymorphism, the CC genotype of the T950C polymorphism, and the CC genotype of
      the G1181C polymorphism were significantly higher in patients with carotid plaque
      than in controls (21.5% versus 10.9% , P<0.01; 15.8% versus 7.6%, P<0.01; and
      20.3% versus 10.9%, P<0.01, respectively) and that these polymorphisms were
      associated with high serum OPG levels (4.02 [3.07] versus 2.94 [1.81] pmol/L;
      P<0.01), which were significantly higher in patients with unstable
      atherosclerotic plaques (5.86 [4.02] versus 3.53 [1.87] pmol/L; P<0.01).
      CONCLUSIONS: The TNFRSF11B gene polymorphisms studied are associated with high
      serum OPG levels and might be potential markers for plaque instability.

PMID- 21903967
TI  - Diastolic carotid artery wall shear stress is associated with cerebral infarcts
      and periventricular white matter lesions.
AB  - BACKGROUND AND PURPOSE: Low wall shear stress (WSS) is an early marker in the
      development of vascular lesions. The present study aims to assess the
      relationship between diastolic and systolic WSS in the internal carotid artery
      and periventricular (PWML), deep white matter lesions, and cerebral infarcts
      (CI). METHODS: Early, mid, and late diastolic and peak systolic WSS were derived
      from shear rate obtained by gradient echo phase contrast magnetic resonance
      sequences multiplied by individually modeled viscosity. PWML, deep white matter
      lesions, and CI were derived from proton density (PD), T2, and fluid attenuated
      inversion recovery (FLAIR) MRI in 329 participants (70-82 years; PROSPER
      baseline). Analyses were adjusted, if appropriate, for age, gender, intracranial
      volume, and multiple cardiovascular risk factors. RESULTS: Mid-diastolic WSS was
      significantly correlated with the presence of PWML (B=-10.15; P=0.006) and CI (B=
      2.06; P=0.044), but not with deep white matter lesions (B=-1.30; P=0.050;
      adjusted for age, gender, WML, and intracranial volume). After adjustment for
      cardiovascular risk factors, these correlations weakened but remained
      significant. Systolic WSS was not correlated with any of the cerebrovascular
      parameters. CONCLUSIONS: This study is the first to our knowledge to present a
      cross-sectional correlation between carotid artery WSS and cerebrovascular
      pathology such as PWML and CI in a large population. Furthermore, it shows that
      diastolic hemodynamics may be more important than systolic or mean hemodynamics.
      Future studies exploring vascular hemodynamic damage should focus on diastolic
      WSS.

PMID- 21903968
TI  - The cardioprotective effect of mildronate is diminished after co-treatment with L
      carnitine.
AB  - Mildronate, an inhibitor of L-carnitine biosynthesis and uptake, is a
      cardioprotective drug whose mechanism of action is thought to rely on the changes
      in concentration of L-carnitine in heart tissue. In the present study, we
      compared the cardioprotective effect of mildronate (100 mg/kg) and a combination
      of mildronate and L-carnitine (100 + 100 mg/kg) administered for 14 days with
      respect to the observed changes in l-carnitine level and carnitine
      palmitoyltransferase I (CPT-I)-dependent fatty acid metabolism in the heart
      tissues. Concentrations of L-carnitine and its precursor gamma-butyrobetaine
      (GBB) were measured by ultraperformance liquid chromatography with tandem mass
      spectrometry. In addition, mitochondrial respiration, activity of CPT-I, and
      expression of CPT-IA/B messenger RNA (mRNA) were measured. Isolated rat hearts
      were subjected to ischemia-reperfusion injury. Administration of mildronate
      induced a 69% decrease in L-carnitine concentration and a 6-fold increase in GBB
      concentration in the heart tissue as well as a 27% decrease in CPT-I-dependent
      mitochondrial respiration on palmitoyl-coenzyme A. In addition, mildronate
      treatment induced a significant reduction in infarct size and also diminished the
      ischemia-induced respiration stimulation by exogenous cytochrome c. Treatment
      with a combination had no significant impact on L-carnitine concentration, CPT-I
      dependent mitochondrial respiration, and infarct size. Our results demonstrated
      that the mildronate-induced decrease in L-carnitine concentration, concomitant
      decrease in fatty acid transport, and maintenance of the intactness of outer
      mitochondrial membrane in heart mitochondria are the key mechanisms of action for
      the anti-infarction activity of mildronate.

PMID- 21903969
TI  - Reduction in the exposure to being out-of-position among car occupants who used a
      sleeping device.
AB  - BACKGROUND: This study assesses the impact on safety of a system designed to
      enhance sleep in car passengers. The system holds the head posteriorly and limits
      its rotation in the sagittal and frontal planes, modifying the occupant's head
      position. This device may have an influence on the interaction between the
      occupant and the vehicle restraint systems. METHODS: It was a randomised,
      prospective, single-blind, cross-over controlled study in which 41 volunteers
      were exposed to using the system while riding as car passengers. Whether the
      device influenced the posture of the occupants and prevented them from adopting
      out-of-position (OOP) configurations was also analysed. Occupants were videotaped
      while they were using both the innovative system (cases) and their normal
      sleeping device (controls), if any. RESULTS: Controls were exposed to OOP
      situations in 825 occasions (18.4%; 95% CI 17.3% to 19.6%), while cases were
      exposed in 416 occasions (9.3%; 95% CI 8.4% to 10.2%). The paper also analysed
      how many cases and controls were exposed at least once to a particular event and
      how frequent a single participant incurred in an OOP situation. In both cases,
      the innovative device showed a reduction in exposition. When OOP situations were
      grouped into severe, moderate and minor events, the innovative device produced a
      statistically significant reduction in the occurrence of severe and moderate
      events. CONCLUSIONS: A device originally designed to improve comfort and rest in
      car passengers has been found to reduce the exposure of the occupants to being
      OOP while resting in the car. TRIAL REGISTRATION NUMBER:
      http://www.ClinicalTrials.gov, NCT01062295.

PMID- 21903970
TI  - Sarcoidosis presenting as dilated cardiomyopathy.

PMID- 21903971
TI  - Serum osteoprotegerin and sex steroid levels in patients with prostate cancer.
AB  - The relationship between sex steroids and osteoprotegerin (OPG) in patients  with
      prostate cancer is not well established. Our aim was to evaluate serum  OPG
      levels in patients with prostate cancer and its relationship with sex  steroids,
      bone mineral density, bone turnover markers, and fractures. We  performed a cross
      sectional study including 91 patients with prostate cancer.  We determined: bone
      mineral density by dual-energy x-ray absorptiometry, bone  turnover markers,
      serum levels of sex steroids and osteoprotegerin, and  prevalent radiographic
      vertebral fractures. Serum OPG levels were higher in  patients with vertebral
      fractures (8.02 +/- 2.0 vs 4.91 +/- 0.28  pmol/L; P < .05). OPG level and the
      duration of hormonal therapy  were related (r = 0.299, P = .004), but this
      association did  not persist after adjustment for age. In patients without
      androgen deprivation  therapy, serum OPG levels were correlated with the levels
      of total  testosterone (r = 0.508, P = .001) and bioavailable  testosterone (r =
      0.311, P = .037). In patients receiving  androgen deprivation therapy, serum OPG
      levels were correlated with levels of  total estradiol (r = 0.199, P = .18),
      bioavailable estradiol  (r = 0.37, P = .009), and free estradiol (r =  0.349, P =
      .016). In conclusion, in patients with prostate cancer  treated with androgen
      deprivation therapy, serum OPG levels were correlated  with the levels of total
      estradiol, bioavailable estradiol, and free  estradiol. Our hypothesis is that in
      patients with androgen deprivation  therapy, the higher relative estrogen levels
      could stimulate OPG production in  response to the higher resorption state.
      Future prospective studies are needed  to clarify the role of OPG in androgen
      deprivation therapy-mediated bone  loss.

PMID- 21903972
TI  - Association of lactate, intracellular pH, and intracellular calcium during
      capacitation and acrosome reaction: contribution of hamster sperm
      dihydrolipoamide dehydrogenase, the E3 subunit of pyruvate dehydrogenase complex.
AB  - The role of dihydrolipoamide dehydrogenase (DLD), the E3 subunit of the  pyruvate
      dehydrogenase complex (PDHc) in hamster sperm capacitation and  acrosome reaction
      has been implicated previously. In this study, attempt has  been made to
      understand DLD/PDHc involvement from the perspective of  pyruvate/lactate
      metabolism. Inhibition of DLD was achieved by the use of a  specific inhibitor, 5
      methoxyindole-2-carboxylic acid. It was seen that  5-methoxyindole-2-carboxylic
      acid-treated spermatozoa with inhibited DLD  (and PDHc) activity had lactate
      accumulation, which caused an initial lowering  of the intracellular pH and
      calcium and an eventual block in capacitation and  acrosome reaction.
      Collectively, the data reveal a significant contribution of  the metabolic
      enzymes DLD and PDHc to lactate regulation in hamster  spermatozoa during
      capacitation and acrosome reaction. Additionally, the  importance of lactate
      regulation in the maintenance of sperm intracellular pH  and calcium, two
      important physiologic factors essential for sperm  capacitation and acrosome
      reaction, has also been established.

PMID- 21903973
TI  - Effect of relaxin on human sperm functions.
AB  - Relaxin is a circulating hormone with functions in pregnancy, parturition,  and
      other aspects of female reproduction. It is also secreted from the  prostate
      gland into the seminal fluid; however, the role of relaxin in male  reproduction
      is debated. Studies conducted in the past have suggested possible  actions on
      human spermatozoa, but the data were contrasting. Here, we show  that the relaxin
      receptor RXFP1 (Relaxin Family Peptide Receptor 1) is  expressed in human
      spermatozoa, and it mainly localizes in the astrodome. In  vitro studies on human
      sperm demonstrated that this hormone attenuates the  natural decline in sperm
      motility and maintains higher mitochondrial activity  and lower apoptosis level.
      Furthermore, relaxin induced an increase in sperm  hyperactivation, intracellular
      calcium and cAMP, and acrosome reaction. These  effects were abolished by the use
      of the specific anti-RXFP1 antibody. Relaxin  concentrations were low in the
      blood  (x +/- SD, 0.16 +/- 0.03 nM)  and very high in the seminal plasma (x  +/-
      SD, 10.3 +/- 4.0 nM), confirming its secretion mainly by the  prostate. Taken
      together, these data demonstrate that relaxin influences  positively many sperm
      functions linked to fertilizing ability, and it  preserves sperm functionality,
      with possible practical value in assisted  reproduction techniques.

PMID- 21903974
TI  - Do additional inputs change maximal voluntary motor unit firing rates after
      spinal cord injury?
AB  - BACKGROUND: Motor unit firing frequencies are low during maximal voluntary
      contractions (MVCs) of human thenar muscles impaired by cervical spinal cord
      injury (SCI). OBJECTIVE: This study aimed to examine whether thenar motor unit
      firing frequencies increase when driven by both maximal voluntary drive and other
      concurrent inputs compared with an MVC alone. METHODS: Motor unit firing rates,
      force, and surface electromyographic activity (EMG) were compared across 2
      contractions: (a) MVC alone and (b) MVC combined with another input (combination
      contraction). Other inputs (conditions) included vibration, heat, or cold applied
      to the anterior surface of the forearm, electrical stimulation delivered to the
      anterior surface of the middle finger, a muscle spasm, or a voluntary contraction
      of the contralateral thenar muscles against resistance. RESULTS: The maximal
      firing frequency (n = 68 units), force, and electromyographic activity (n = 92
      contraction pairs) were all significantly higher during the combined contractions
      compared with MVCs alone. There was a 3-way interaction between contraction,
      condition, and subject for maximal motor unit firing rates, force, and EMG. Thus,
      combined contraction responses were different for conditions across subjects.
      Some conditions (eg, a muscle spasm) resulted in more effective and more frequent
      responses (increases in unit firing frequency, force, EMG in >50% contractions)
      than others. Recruitment of new units also occurred in combined contractions.
      CONCLUSIONS: Motoneurons are still responsive to additional afferent inputs from
      various sources when rate modulation from voluntary drive is limited by SCI.
      Individuals with SCI may be able to combine inputs to control functional tasks
      they cannot perform with voluntary drive alone.

PMID- 21903975
TI  - Pilot trial of distributed constraint-induced therapy with trunk restraint to
      improve poststroke reach to grasp and trunk kinematics.
AB  - BACKGROUND: Constraint-induced therapy (CIT) is effective in improving upper
      extremity motor function, but evidence is lacking about effectiveness grasp and
      trunk control. OBJECTIVE: This study investigated whether distributed CIT
      combined with trunk restraint (dCIT + TR) benefited movement kinematics of
      grasping and the trunk, as well as motor ability of the upper extremity, more
      than dCIT alone. METHODS: A total of 45 stroke participants received 2 hours of
      dCIT + TR, dCIT, or the dose-matched control intervention for 3 weeks. Movement
      kinematics, motor ability, and daily function were the outcome measures. Movement
      kinematics included grasping, joint range, and trunk movement at various phases
      of reach-to-grasp tasks. Motor ability and daily function of all participants
      were evaluated using the Fugl-Meyer Assessment and the Motor Activity Log.
      RESULTS: Four to 5 participants in each group were not included for kinematic
      analysis because of their inability to grasp a can. The dCIT + TR group showed
      better preplanned grasping movement and less trunk motion at the early phase of
      the reach-to-grasp movements than the dCIT or control groups. Compared with the
      controls, the dCIT + TR participants showed better motor ability in the overall
      and distal arm scores of the Fugl-Meyer Assessment. The dCIT + TR and dCIT
      participants demonstrated significantly greater functional use of the affected
      arm. CONCLUSIONS: Administering dCIT + TR produced additional benefits by
      improving grasping control and reversing the compensatory trunk movement at the
      early phase of a reach-to-grasp movement. The use of experimental tasks beyond
      and within arm's length might improve our understanding of optimal upper
      extremity rehabilitation.

PMID- 21903976
TI  - Acquired control of ventral premotor cortex activity by feedback training: an
      exploratory real-time FMRI and TMS study.
AB  - BACKGROUND: Despite the availability of various options for movement restoration
      in stroke patients, there is no effective treatment for patients who show little
      or no functional recovery of upper limb motor function. OBJECTIVE: The present
      study explored the feasibility of real-time functional magnetic resonance imaging
      brain-computer interface (fMRI-BCI) as a new tool for rehabilitation of this
      patient population. METHODS: Healthy adults and chronic subcortical stroke
      patients with residual movement were trained for 3 days to regulate the blood
      oxygenation level dependent (BOLD) response in the ventral premotor cortex (PMv),
      a secondary motor area with extensive anatomic connections with the primary motor
      cortex. Effect of learned modulation of the PMv was evaluated with BOLD signal
      changes across training sessions, transcranial magnetic stimulation (TMS), and a
      visuomotor task. RESULTS: fMRI-BCI feedback training showed learning with a
      significantly increasing BOLD signal in the PMv over sessions. Participants'
      capability to learn self-regulation was found to depend linearly on intracortical
      facilitation and correlated negatively with intracortical inhibition measured by
      TMS prior to feedback training. After training, intracortical inhibition
      decreased significantly with the volitional increase of the BOLD response in the
      PMv, indicating a beneficial effect of self-regulation training on motor cortical
      output. CONCLUSION: The study provides first evidence for the therapeutic
      potential of fMRI-BCI in stroke rehabilitation.

PMID- 21903978
TI  - Using a pictorial-modified stroop task to explore the sexual interests of sexual
      offenders against children.
AB  - The results of two studies are reported examining the utility of a pictorial
      modified Stroop task (P-MST) in the assessment of sexual interest in a sample of
      nonoffending participants and of sexual offenders against children. A mixed
      factorial design was adopted for both. Nine gay and 12 straight participants took
      part in the first study which found that participants typically had attentional
      bias on the P-MST that was in line with their stated sexual interests. Twenty
      four sexual offenders against children and 24 control participants took part in
      the second study. Again results indicated that the task was tapping into the
      participants' stated sexual interests. Furthermore, extrafamilial offenders and
      offenders with an admitted sexual interest in children demonstrated the greatest
      mean bias for child stimuli relative to adult stimuli. A cautious interpretation
      of the results was recommended, given the sample size in the study, the
      heterogeneity of the sample, differences in cognitive speed among offenders and
      controls and other methodological caveats.

PMID- 21903979
TI  - Using FDA reports to inform a classification for health information technology
      safety problems.
AB  - OBJECTIVE: To expand an emerging classification for problems with health
      information technology (HIT) using reports submitted to the US Food and Drug
      Administration Manufacturer and User Facility Device Experience (MAUDE) database.
      DESIGN: HIT events submitted to MAUDE were retrieved using a standardized search
      strategy. Using an emerging classification with 32 categories of HIT problems, a
      subset of relevant events were iteratively analyzed to identify new categories.
      Two coders then independently classified the remaining events into one or more
      categories. Free-text descriptions were analyzed to identify the consequences of
      events. MEASUREMENTS: Descriptive statistics by number of reported problems per
      category and by consequence; inter-rater reliability analysis using the kappa
      statistic for the major categories and consequences. RESULTS: A search of 899 768
      reports from January 2008 to July 2010 yielded 1100 reports about HIT. After
      removing duplicate and unrelated reports, 678 reports describing 436 events
      remained. The authors identified four new categories to describe problems with
      software functionality, system configuration, interface with devices, and network
      configuration; the authors' classification with 32 categories of HIT problems was
      expanded by the addition of these four categories. Examination of the 436 events
      revealed 712 problems, 96% were machine-related, and 4% were problems at the
      human-computer interface. Almost half (46%) of the events related to hazardous
      circumstances. Of the 46 events (11%) associated with patient harm, four deaths
      were linked to HIT problems (0.9% of 436 events). CONCLUSIONS: Only 0.1% of the
      MAUDE reports searched were related to HIT. Nevertheless, Food and Drug
      Administration reports did prove to be a useful new source of information about
      the nature of software problems and their safety implications with potential to
      inform strategies for safe design and implementation.

PMID- 21903980
TI  - Herpes simplex virus type 2 serological testing and psychosocial harm: a
      systematic review.
AB  - BACKGROUND: Serological testing for herpes simplex virus (HSV) type 2 in persons
      without a history of genital herpes is not recommended, partly because of
      concerns that an HSV-2 diagnosis would lead to negative psychosocial sequelae.
      This review aimed to examine the evidence regarding the psychosocial effects of
      HSV-2 serological testing. METHODS: Eight electronic databases were searched for
      empirical studies indexed before March 2010. Abstracts from relevant conferences
      were reviewed and senior authors contacted to find unpublished materials.
      Eligible studies examined participants without a history of genital herpes who
      underwent HSV-2 serological testing and reported data from at least one
      quantitative or qualitative psychosocial assessment conducted after receiving HSV
      results. RESULTS: Of nine studies that satisfied the inclusion criteria, seven
      reported that HSV-2 diagnosis by serological test did not have a persistent
      negative impact on 309 participants' mental health or sexual attitude and
      satisfaction. Two studies reported a negative impact of testing; one found that
      five HSV-2-seropositive college students had increased distress 3 months post
      testing compared with HSV-2-negative individuals, and the other found self
      reports of sexual undesirability up to 1 year after diagnosis in some people. The
      perceived severity of a genital herpes diagnosis was moderately severe for
      participants before testing; however, post-testing, the reported severity of a
      herpes diagnosis was lower among those testing HSV-2 positive. CONCLUSIONS: HSV-2
      diagnosis by type-specific serological testing did not result in long-term
      psychosocial harm in most persons without an identified history of genital
      herpes. Concerns about sustained emotional impact should not deter clinicians
      from offering HSV-2 serological testing to appropriate patients.

PMID- 21903981
TI  - The effect of racial origin on total body water volume in peritoneal dialysis
      patients.
AB  - BACKGROUND AND OBJECTIVES: Peritoneal dialysis adequacy is typically assessed by
      urea clearance corrected for total body water (TBW) on the basis of
      anthropomorphic equations, which do not readily take into account changes in body
      composition, which may vary between ethnic groups. To determine whether ethnicity
      could affect estimates of peritoneal dialysis adequacy, we compared TBW estimated
      by anthropomorphic equations and that measured by multifrequency bioimpedance
      spectroscopy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We calculated TBW in
      600 healthy adult peritoneal dialysis outpatient attending two tertiary
      university hospitals serving an inner-city multiethnic population who had TBW
      measured by multifrequency bioimpedance spectroscopy performed. RESULTS: 600
      adult peritoneal dialysis patients were studied: mean age, 56.7 +/- 0.6 years;
      54.2% men; 29.7% diabetic; mean body mass index, 26.1 +/- 0.2; 47.3% Caucasian;
      29.2% South Asian; 12.8% African/Afro-Caribbean. Total body water was calculated
      using several anthropomorphic equations and was higher than that calculated
      MEASURED BY MF-BIS for all ethnic groups, apart from African/Afro-Caribbeans,
      with the greatest difference between Watson calculated TBW and multifrequency
      bioelectrical impedance spectroscopy 12.3 +/- 0.6% for the South Asians, 9.0 +/-
      2.6% for Far Eastern Asians, 2.8 +/- 0.6% Caucasians, and -0.2 +/- 1.5% for
      African/Afro-Caribbeans. CONCLUSIONS: In this United Kingdom-based multiethnic
      population, body composition differed particularly for the South Asian patients
      compared with Caucasians and African/Afro-Caribbeans. Overestimation of TBW by
      anthropomorphic-based equations would lead to a lower calculation of Kt/V(urea),
      which may lead to changes in peritoneal dialysis prescription to achieve clinical
      standard targets and also affect studies examining the relationship between Kt/V
      and survival.

PMID- 21903982
TI  - Warfarin in atrial fibrillation patients with moderate chronic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: The efficacy of adjusted-dose warfarin for prevention
      of stroke in atrial fibrillation patients with stage 3 chronic kidney disease
      (CKD) is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Patients with
      stage 3 CKD participating in the Stroke Prevention in Atrial Fibrillation 3
      trials were assessed to determine the effect of warfarin anticoagulation on
      stroke and major hemorrhage, and whether CKD status independently contributed to
      stroke risk. High-risk participants (n = 1044) in the randomized trial were
      assigned to adjusted-dose warfarin (target international normalized ratio 2 to 3)
      versus aspirin (325 mg) plus fixed, low-dose warfarin (subsequently shown to be
      equivalent to aspirin alone). Low-risk participants (n = 892) all received 325 mg
      aspirin daily. The primary outcome was ischemic stroke (96%) or systemic embolism
      (4%). RESULTS: Among the 1936 participants in the two trials, 42% (n = 805) had
      stage 3 CKD at entry. Considering the 1314 patients not assigned to adjusted-dose
      warfarin, the primary event rate was double among those with stage 3 CKD (hazard
      ratio 2.0, 95% CI 1.2, 3.3) versus those with a higher estimated GFR (eGFR).
      Among the 516 participants with stage 3 CKD included in the randomized trial,
      ischemic stroke/systemic embolism was reduced 76% (95% CI 42, 90; P < 0.001) by
      adjusted-dose warfarin compared with aspirin/low-dose warfarin; there was no
      difference in major hemorrhage (5 patients versus 6 patients, respectively).
      CONCLUSIONS: Among atrial fibrillation patients participating in the Stroke
      Prevention in Atrial Fibrillation III trials, stage 3 CKD was associated with
      higher rates of ischemic stroke/systemic embolism. Adjusted-dose warfarin
      markedly reduced ischemic stroke/systemic embolism in high-risk atrial
      fibrillation patients with stage 3 CKD.

PMID- 21903985
TI  - The 2010 nephrology quiz and questionnaire: part 2.
AB  - Presentation of the Nephrology Quiz and Questionnaire (NQQ) has become an annual
      "tradition" at the meetings of the American Society of Nephrology. It is a very
      popular session judged by consistently large attendance. Members of the audience
      test their knowledge and judgment on a series of case-oriented questions prepared
      and discussed by experts. They can also compare their answers in real time, using
      audience response devices, to those of program directors of nephrology training
      programs in the United States, acquired through an Internet-based questionnaire.
      As in the past, the topics covered were transplantation, fluid and electrolyte
      disorders, end-stage renal disease and dialysis, and glomerular disorders. Two
      challenging cases representing each of these categories along with single best
      answer questions were prepared by a panel of experts (Drs. Hricik, Palmer,
      Bargman, and Fervenza, respectively). The "correct" and "incorrect" answers then
      were briefly discussed, after the audience responses and the results of the
      questionnaire were displayed. The 2010 version of the NQQ was exceptionally
      challenging, and the audience, for the first time, gained a better overall
      correct answer score than the program directors, but the margin was small. Last
      month we presented the transplantation and fluid and the electrolyte cases; in
      this issue we present the remaining end-stage renal disease and dialysis and the
      glomerular disorder cases. These articles try to recapitulate the session and
      reproduce its educational value for a larger audience--that of the readers of the
      Clinical Journal of the American Society of Nephrology. Have fun.

PMID- 21903983
TI  - Cardiac magnetic resonance assessment of left ventricular mass in autosomal
      dominant polycystic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD)
      is associated with a substantial cardiovascular disease burden including early
      onset hypertension, intracranial aneurysms, and left ventricular hypertrophy
      (LVH). A 41% prevalence of LVH has been reported in ADPKD, using
      echocardiographic assessment of LV mass (LVM). The HALT PKD study was designed to
      assess the effect of intensive angiotensin blockade on progression of total
      kidney volume and LVM. Measurements of LVM were performed using cardiac magnetic
      resonance (MR). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Five hundred forty
      three hypertensive patients with GFR >60 ml/min per 1.73 m(2) underwent MR
      assessment of LVM at baseline. LVM was adjusted for body surface area and
      expressed as LVM index (LVMI; g/m(2)). RESULTS: Baseline BP was 125.1 +/-
      14.5/79.3 +/- 11.6 mmHg. Average duration of hypertension was 5.79 years. Prior
      use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers
      was present in 59.5% of patients. The prevalence of LVH assessed using nonindexed
      LVM (g) was 3.9% (n = 21, eight men and 13 women) and 0.93% (n = 5, one man and
      four women) using LVMI (g/m(2)). In exploratory analyses, the prevalence of LVH
      using LVM indexed to H(2.7), and the allometric index ppLVmass(HW), ranged from
      0.74% to 2.23% (n = 4 to 12). Multivariate regression showed significant direct
      associations of LVMI with systolic BP, serum creatinine, and albuminuria;
      significant inverse associations with LVMI were found with age and female gender.
      CONCLUSIONS: The prevalence of LVH in hypertensive ADPKD patients <50 years of
      age with short duration of hypertension, and prior use of angiotensin-converting
      enzyme inhibitors/angiotensin receptor blockers is low. Early BP intervention in
      ADPKD may have decreased LVH and may potentially decrease cardiovascular
      mortality.

PMID- 21903984
TI  - Tolvaptan in autosomal dominant polycystic kidney disease: three years'
      experience.
AB  - BACKGROUND AND OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD),
      a frequent cause of end-stage renal disease, has no cure. V2-specific vasopressin
      receptor antagonists delay disease progression in animal models. DESIGN, SETTING,
      PARTICIPANTS, AND MEASUREMENTS: This is a prospectively designed analysis of
      annual total kidney volume (TKV) and thrice annual estimated GFR (eGFR)
      measurements, from two 3-year studies of tolvaptan in 63 ADPKD subjects randomly
      matched 1:2 to historical controls by gender, hypertension, age, and baseline TKV
      or eGFR. Prespecified end points were group differences in log-TKV (primary) and
      eGFR (secondary) slopes for month 36 completers, using linear mixed model (LMM)
      analysis. Sensitivity analyses of primary and secondary end points included LMM
      using all subject data and mixed model repeated measures (MMRM) of change from
      baseline at each year. Pearson correlation tested the association between log-TKV
      and eGFR changes. RESULTS: Fifty-one subjects (81%) completed 3 years of
      tolvaptan therapy; all experienced adverse events (AEs), with AEs accounting for
      six of 12 withdrawals. Baseline TKV (controls 1422, tolvaptan 1635 ml) and eGFR
      (both 62 ml/min per 1.73 m(2)) were similar. Control TKV increased 5.8% versus
      1.7%/yr for tolvaptan (P < 0.001, estimated ratio of geometric mean 0.96 [95%
      confidence interval 0.95 to 0.97]). Corresponding annualized eGFR declined: -2.1
      versus -0.71 ml/min per 1.73 m(2)/yr (P = 0.01, LMM group difference 1.1 ml/min
      per 1.73 m(2)/yr [95% confidence interval 0.24 to 1.9]). Sensitivity analyses
      including withdrawn subjects were similar, whereas MMRM analyses were significant
      at each year for TKV and nonsignificant for eGFR. Increasing TKV correlated with
      decreasing eGFR (r = -0.21, P < 0.01). CONCLUSION: ADPKD cyst growth progresses
      more slowly with tolvaptan than in historical controls, but AEs are common.

PMID- 21903986
TI  - Interaction of time-varying albumin and phosphorus on mortality in incident
      dialysis patients.
AB  - BACKGROUND AND OBJECTIVES: Hypoalbuminemia and hyperphosphatemia have been shown
      to be strong predictors of mortality in dialysis patients that might not be
      independent from each other. We prospectively investigated the relationship and
      interaction between serum albumin and phosphorus with all-cause mortality in an
      inception cohort of incident dialysis patients. DESIGN, SETTING, PARTICIPANTS, &
      MEASUREMENTS: We followed 235 incident dialysis patients in a prospective single
      center cohort study (INVOR study) applying a time-dependent Cox proportional
      hazards model using all measured laboratory values (2887 albumin and 10306
      phosphorus values). RESULTS: Eighty-two patients (35%) died during a median
      follow-up of 35.1 months. Albumin was inversely associated with mortality (hazard
      ratio [95% confidence interval]: 0.23 [0.14 to 0.36]; P < 0.001), whereas higher
      phosphorus concentrations showed a trend to an increasing risk for mortality
      (hazard ratio 1.57 [95% confidence interval 0.97 to 2.54]; P = 0.07).
      Importantly, we observed a significant interaction between albumin and phosphorus
      (P = 0.01). The lowest risk was found with concurrent low phosphorus and high
      albumin values, whereas risk was increased with either concurrent low phosphorus
      and low albumin values or high phosphorus and high albumin values. CONCLUSIONS:
      In incident dialysis patients the associations of serum phosphorus and albumin
      concentrations with mortality are modified by each other over time. Phosphorus
      lowering interventions that concomitantly can cause a fall in serum albumin level
      may be harmful and warrant additional studies. If confirmed, epidemiologic
      studies and therapeutic guidelines aiming for target values should consider this
      interplay.

PMID- 21903987
TI  - Glomerular hyperfiltration and renal progression in children with autosomal
      dominant polycystic kidney disease.
AB  - BACKGROUND AND OBJECTIVES: The purpose of this study was to determine whether
      glomerular hyperfiltration (GH) occurring early in autosomal dominant polycystic
      kidney disease (ADPKD) is indicative of more rapid disease progression in
      children. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: One hundred eighty
      children with ADPKD (ages 4 to 18 years) with normal renal function were examined
      by renal ultrasound. Renal volume was calculated using a standard formula for a
      modified ellipsoid. Creatinine clearance was calculated from serum creatinine and
      24-hour urine creatinine. GH was defined as creatinine clearance >=140 ml/min per
      1.73 m(2). RESULTS: Thirty-two children had GH (mean age 11.4 +/- 3.6 years) and
      148 had normal renal function (mean age 10.8 +/- 3.9 years). Patients with GH at
      baseline demonstrated an increased rate of total renal volume growth (beta: rate
      of change = +19.3 +/- 10.8 cm(3)/year) over 5 years compared with those without
      GH at baseline (beta = -4.3 +/- 7.7 cm(3)/year), P = 0.008. Those with GH at
      baseline experienced a faster decline in creatinine clearance in subsequent years
      (beta = -5.0 +/- 0.8 ml/min per 1.73 m(2) per year) compared with those without
      GH at baseline (beta = +1.0 +/- 0.4 ml/min per 1.73 m(2) per year), P < 0.0001.
      CONCLUSIONS: This study revealed that occurrence of GH in ADPKD children is
      associated with a significantly faster decline in renal function and higher rate
      of kidney enlargement over time. GH combined with the increased renal volume may
      therefore be used as an early marker for a more severe progression of ADPKD in
      children.

PMID- 21903988
TI  - Acute kidney injury episodes and chronic kidney disease risk in diabetes
      mellitus.
AB  - BACKGROUND AND OBJECTIVES: Prior studies have examined long-term outcomes of a
      single acute kidney injury (AKI) event in hospitalized patients. We examined the
      effects of AKI episodes during multiple hospitalizations on the risk of chronic
      kidney disease (CKD) in a cohort with diabetes mellitus (DM). DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: A total of 4082 diabetics were followed from
      January 1999 until December 2008. The primary outcome was reaching stage 4 CKD
      (GFR of <30 ml/min per 1.73 m(2)). AKI during hospitalization was defined as >0.3
      mg/dl or a 1.5-fold increase in creatinine relative to admission. Cox survival
      models examined the effect of first AKI episode and up to three episodes as time
      dependent covariates, on the risk of stage 4 CKD. Covariates included demographic
      variables, baseline creatinine, and diagnoses of comorbidities including
      proteinuria. RESULTS: Of the 3679 patients who met eligibility criteria (mean age
      = 61.7 years [SD, 11.2]; mean baseline creatinine = 1.10 mg/dl [SD, 0.3]), 1822
      required at least one hospitalization during the time under observation (mean =
      61.2 months [SD, 25]). Five hundred thirty of 1822 patients experienced one AKI
      episode; 157 of 530 experienced >=2 AKI episodes. In multivariable Cox
      proportional hazards models, any AKI versus no AKI was a risk factor for stage 4
      CKD (hazard ratio [HR], 3.56; 95% confidence interval [CI], 2.76, 4.61); each AKI
      episode doubled that risk (HR, 2.02; 95% CI, 1.78, 2.30). CONCLUSIONS: AKI
      episodes are associated with a cumulative risk for developing advanced CKD in
      diabetes mellitus, independent of other major risk factors of progression.

PMID- 21903989
TI  - Effect of dialysis modality on survival of hepatitis C-infected ESRF patients.
AB  - BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) infection is associated with
      increased mortality and morbidity in end-stage renal failure (ESRF) patients.
      Despite a lower incidence and risk of transmission of HCV infection with
      peritoneal dialysis (PD), the optimal dialysis modality for HCV-infected ESRF
      patients is not known. The aim of this study was to evaluate the impact of
      dialysis modality on the survival of HCV-infected ESRF patients. DESIGN, SETTING,
      PARTICIPANTS, & MEASUREMENTS: The study included all adult incident ESRF patients
      in Australia and New Zealand who commenced dialysis between January 1, 1994, and
      December 31, 2008, and were HCV antibody-positive at the time of dialysis
      commencement. Time to all-cause mortality was compared between hemodialysis (HD)
      and PD according to modality assignment at day 90, using Cox proportional hazards
      model analysis. RESULTS: A total of 424 HCV-infected ESRF patients commenced
      dialysis during the study period and survived for at least 90 days (PD n = 134;
      HD n = 290). Mortality rates were comparable between PD and HD in the first year
      (10.7 versus 13.8 deaths per 100 patient-years, respectively; adjusted hazard
      ratio [HR] 0.65, 95% CI 0.34 to 1.26) and thereafter (20 versus 15.9 deaths per
      100 patient-years, respectively; HR 1.27, 95% CI 0.86 to 1.88). CONCLUSIONS: The
      survival of HCV-infected ESRF patients is comparable between PD and HD.

PMID- 21903991
TI  - Phosphate REINs in the renoprotective benefit of ACE inhibition.

PMID- 21903990
TI  - Fibroblast growth factor 23 in patients undergoing peritoneal dialysis.
AB  - BACKGROUND AND OBJECTIVES: Fibroblast growth factor 23 (FGF23) is an independent
      risk factor for mortality in patients with ESRD. Before FGF23 testing can be
      integrated into clinical practice of ESRD, further understanding of its
      determinants is needed. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In a study
      of 67 adults undergoing peritoneal dialysis, we tested the hypothesis that longer
      dialysis vintage and lower residual renal function and renal phosphate clearance
      are associated with higher FGF23. We also compared the monthly variability of
      FGF23 versus parathyroid hormone (PTH) and serum phosphate. RESULTS: In
      unadjusted analyses, FGF23 correlated with serum phosphate (r = 0.66, P < 0.001),
      residual renal function (r = -0.37, P = 0.002), dialysis vintage (r = 0.31, P =
      0.01), and renal phosphate clearance (r = -0.38, P = 0.008). In adjusted
      analyses, absence of residual renal function and greater dialysis vintage
      associated with higher FGF23, independent of demographics, laboratory values,
      peritoneal dialysis modality and adequacy, and treatment with vitamin D analogs
      and phosphate binders. Urinary and dialysate FGF23 clearances were minimal. In
      three serial monthly measurements, within-subject variability accounted for only
      10% of total FGF23 variability compared with 50% for PTH and 60% for serum
      phosphate. CONCLUSIONS: Increased serum phosphate, loss of residual renal
      function, longer dialysis vintage, and lower renal phosphate clearance are
      associated with elevated FGF23 levels in ESRD patients undergoing peritoneal
      dialysis. FGF23 may be a more stable marker of phosphate metabolism in ESRD than
      PTH or serum phosphate.

PMID- 21903992
TI  - Membranous nephropathy with crescents.
AB  - Membranous nephropathy is a common cause of nephrotic syndrome in adults and can
      be primary or secondary to systemic lupus erythematosus, chronic infection, or
      drugs. Rapid decline in renal function in patients with membranous nephropathy
      may be due to renal vein thrombosis, malignant hypertension, or an additional
      superimposed destructive process involving the renal parenchyma. Crescents are
      rare in primary membranous nephropathy and thus suggest another underlying
      disease process, such as combined membranous and focal or diffuse lupus
      nephritis. However, in some patients with membranous nephropathy and crescents,
      the crescentic lesion may be due to a distinct, separate disease process, such as
      anti-glomerular basement membrane antibodies or anti-neutrophil cytoplasmic
      antibodies-related pauci-immune glomerulonephritis. Here we describe a case with
      such renal biopsy findings, review previous reported cases, and discuss possible
      implications for pathogenesis of the coexistence of these lesions.

PMID- 21903994
TI  - Autoantibodies: what's in their teeth?

PMID- 21903993
TI  - AMPK potentiates hypertonicity-induced apoptosis by suppressing NFkappaB/COX-2 in
      medullary interstitial cells.
AB  - Cells residing in the hypertonic, hypoxic renal medulla depend on dynamic
      adaptation mechanisms to respond to changes in energy supply and demand. The
      serine/threonine kinase 5'-AMP protein kinase (AMPK) is a sensor of cellular
      energy status, but whether it contributes to the survival of cells in the renal
      medulla is unknown. Here, hypertonic conditions induced a decrease in AMPK
      phosphorylation within 12 hours in renal medullary interstitial cells (RMIC),
      followed by a gradual return to baseline levels. Activation of AMPK markedly
      increased hypertonicity-induced apoptosis of RMICs and suppressed both
      hypertonicity-induced NFkappaB nuclear translocation and cyclooxygenase-2 (COX-2)
      activation; overexpression of COX-2 significantly attenuated these effects. AMPK
      activation also markedly reduced generation of reactive oxygen species and
      nuclear expression of tonicity-responsive enhancer-binding protein, which
      prevented upregulation of osmoprotective genes. In vivo, pharmacologic activation
      of AMPK led to massive apoptosis of RMICs and renal dysfunction in the setting of
      water deprivation in mice. Taken together, these results identify a critical role
      for AMPK in the maintenance of RMIC viability and suggest that AMPK modulates the
      NFkappaB-COX-2 survival pathway in the renal medulla. Furthermore, this study
      raises safety concerns for the development of AMPK activators as anti-diabetic
      drugs, especially for patients prone to dehydration.

PMID- 21903995
TI  - Exome sequencing reveals cubilin mutation as a single-gene cause of proteinuria.
AB  - In two siblings of consanguineous parents with intermittent nephrotic-range
      proteinuria, we identified a homozygous deleterious frameshift mutation in the
      gene CUBN, which encodes cubulin, using exome capture and massively parallel re
      sequencing. The mutation segregated with affected members of this family and was
      absent from 92 healthy individuals, thereby identifying a recessive mutation in
      CUBN as the single-gene cause of proteinuria in this sibship. Cubulin mutations
      cause a hereditary form of megaloblastic anemia secondary to vitamin B(12)
      deficiency, and proteinuria occurs in 50% of cases since cubilin is coreceptor
      for both the intestinal vitamin B(12)-intrinsic factor complex and the tubular
      reabsorption of protein in the proximal tubule. In summary, we report successful
      use of exome capture and massively parallel re-sequencing to identify a rare,
      single-gene cause of nephropathy.

PMID- 21903996
TI  - Mineralocorticoid receptor mutations and a severe recessive
      pseudohypoaldosteronism type 1.
AB  - Pseudohypoaldosteronism type 1 (PHA1) is a rare genetic disease of
      mineralocorticoid resistance characterized by salt wasting and failure to thrive
      in infancy. Here we describe the first case of a newborn with severe recessive
      PHA1 caused by two heterozygous mutations in NR3C2, gene coding for the
      mineralocorticoid receptor (MR). Independent segregation of the mutations
      occurred in the family, with p.Ser166X being transmitted from the affected father
      and p.Trp806X from the asymptomatic mother Whereas the truncated MR(166X) protein
      was degraded, MR(806X) was expressed both at the mRNA and protein level.
      Functional studies demonstrated that despite its inability to bind aldosterone,
      MR(806X) had partial ligand-independent transcriptional activity. Partial nuclear
      localization of MR(806X) in the absence of hormone was identified as a
      prerequisite to initiate transcription. This exceptional case broadens the
      spectrum of clinical phenotypes of PHA1 and demonstrates that minimal residual
      activity of MR is compatible with life. It also suggests that rare hypomorphic
      NR3C2 alleles may be more common than expected from the prevalence of detected
      PHA1 cases. This might prove relevant for patient's care in neonatal salt losing
      disorders and may affect renal salt handling and blood pressure in the general
      population.

PMID- 21903997
TI  - Current therapy for IgA nephropathy.
AB  - IgA nephropathy (IgAN) is a very common glomerulonephritis worldwide. In this
      review, we discuss therapeutic options in four clinical scenarios encountered in
      patients with IgAN: first is the patient with minor urinary abnormalities where
      the mainstay of treatment is long-term, regular follow-up to detect renal
      progression and hypertension. Second is the typical patient presenting with
      microhematuria, significant but non-nephrotic proteinuria, hypertension, and
      variable degrees of renal failure. Here the mainstay of treatment is optimized
      supportive care. If this does not lower proteinuria below 1 g/d, corticosteroid
      monotherapy may be effective, as long as the GFR is above 50 ml/min. There is
      insufficient data to advocate the use of other immunosuppressive drugs or even
      combination therapy in such patients. Third is the atypical patient with overt
      nephrotic syndrome, or acute or rapidly progressive kidney injury where a
      possible vasculitic form of IgAN should be sought and, if present, treated with
      immunosuppression. In other atypical patients with secondary IgAN, treatment
      should target the underlying primary disease. And fourth is the transplanted
      patient with recurrent IgAN where the mainstay of treatment is optimized
      supportive care.

PMID- 21903998
TI  - Is there something better than the best marker of kidney function?

PMID- 21903999
TI  - Reliability, validity, and precision of a handheld myometer for assessing in vivo
      muscle stiffness.

PMID- 21904000
TI  - Talocrural joint mobilization's lack of effect on postural control in healthy
      subjects.

PMID- 21904001
TI  - The effect of bone-bruise lesions on pain in patients with traumatic knee injury.

PMID- 21904002
TI  - Risk of nutrient inadequacies in elite Canadian athletes with spinal cord injury.
AB  - Energy intakes of adults with spinal cord injury (SCI) have been reported to be
      relatively low, with many micronutrients below recommended amounts, but little is
      known about the diets of athletes with SCI. The purpose of this cross-sectional,
      observational study was to assess energy intakes and estimate the prevalence of
      dietary inadequacy in a sample of elite Canadian athletes with SCI (n = 32).
      Three-day self-reported food diaries completed at home and training camp were
      analyzed for energy (kcal), macronutrients, vitamins, and minerals and compared
      with the dietary reference intakes (DRIs). The prevalence of nutrient inadequacy
      was estimated by the proportion of athletes with mean intakes below the estimated
      average requirement (EAR). Energy intakes were 2,156 +/- 431 kcal for men and
      1,991 +/- 510 kcal for women. Macronutrient intakes were within the acceptable
      macronutrient distribution ranges. While at training camp, >25% of men had
      intakes below the EAR for calcium, magnesium, zinc, riboflavin, folate, vitamin
      B12, and vitamin D. Thiamin, riboflavin, calcium, and vitamin D intakes were
      higher at home than training camp. Over 25% of women had intakes below the EAR
      for calcium, magnesium, folate, and vitamin D, with no significant differences in
      mean intakes between home and training camp. Vitamin/mineral supplement use
      significantly increased men's intakes of most nutrients but did not affect
      prevalence of inadequacy. Women's intakes did not change significantly with
      vitamin/mineral supplementation. These results demonstrate that athletes with SCI
      are at risk for several nutrient inadequacies relative to the DRIs.

PMID- 21904003
TI  - The effect of preoperative quadriceps strength on strength and function after
      anterior cruciate ligament reconstruction.

PMID- 21904004
TI  - Effect of therapeutic exercise versus manual therapy on athletes with chronic low
      back pain.
AB  - Rehabilitation professionals treat individuals suffering from chronic low back
      pain (CLBP) using a variety of treatment approaches including manual therapy and
      the prescription of therapeutic exercises. The use of manual therapy,
      specifically joint mobilization of the lumbar spine, may significantly decrease a
      patient's pain and contribute to improvement in his or her functioning. Exercise
      may also improve pain and functioning, with some patients reporting gains up to 1
      year after the last treatment session.

PMID- 21904005
TI  - Nutrition for synchronized swimming: a review.
AB  - Synchronized swimming enjoys worldwide popularity and has been part of the formal
      Olympic program since 1984. Despite this, relatively little research has been
      conducted on participant nutrition practices and requirements, and there are
      significant gaps in the knowledge base despite the numerous areas in which
      nutrition could affect performance and safety. This review aimed to summarize
      current findings and identify areas requiring further research. Uniform physique
      in team or duet events may be more important than absolute values for muscularity
      or body fat, but a lean and athletic appearance remains key. Synchronized
      swimmers appear to have an increased risk of developing eating disorders, and
      there is evidence of delayed menarche, menstrual dysfunction, and lower bone
      density relative to population norms. Dietary practices remain relatively
      unknown, but micronutrient status for iron and magnesium may be compromised. More
      research is required across all aspects of nutrition status, anthropometry, and
      physiology, and both sports nutrition and sports medicine support may be required
      to reduce risks for participants.

PMID- 21904006
TI  - Peroneal reaction time and ankle sprain risk in healthy adults: a critically
      appraised topic.

PMID- 21904007
TI  - Effectiveness of corticosteroids in the treatment of lateral epicondylosis.

PMID- 21904008
TI  - On the estimate of the two dominant axes of the knee using an instrumented
      spatial linkage.
AB  - This article presents the validation of a technique to assess the appropriateness
      of a 2 degree-of-freedom model for the human knee, and, in which case, the
      dominant axes of flexion/extension and internal/external longitudinal rotation
      are estimated. The technique relies on the use of an instrumented spatial linkage
      for the accurate detection of passive knee kinematics, and it is based on the
      assumption that points on the longitudinal rotation axis describe nearly circular
      and planar trajectories, whereas the flexion/extension axis is perpendicular to
      those trajectories through their centers of rotation. By manually enforcing a
      tibia rotation while bending the knee in flexion, a standard optimization
      algorithm is used to estimate the approximate axis of longitudinal rotation, and
      the axis of flexion is estimated consequently. The proposed technique is
      validated through simulated data and experimentally applied on a 2 degree-of
      freedom mechanical joint. A procedure is proposed to verify the fixed axes
      assumption for the knee model. The suggested methodology could be possibly
      valuable in understanding knee kinematics, and in particular for the design and
      implant of customized hinged external fixators, which have shown to be effective
      in knee dislocation treatment and rehabilitation.

PMID- 21904010
TI  - Fracture resistance and analysis of stress distribution of implant-supported
      single zirconium ceramic coping combination with abutments made of different
      materials.
AB  - The purpose of this study was to compare the fracture resistance and fracture
      mode of single implant-zirconium coping combinations using zirconium and titanium
      abutments and to analyze the stress distribution pattern using three-dimensional
      finite elements analysis. Twenty implants with titanium and zirconium abutments
      were randomly divided into two groups (n = 10) and into resin blocks. Zirconium
      copings were cemented onto the abutments. The specimens were loaded with 135
      degrees  angles to the long axis and the load values at the moment of failure
      were recorded using a universal test machine. Stress levels were calculated
      according to the maximum Von Mises criteria. The fracture resistances for
      titanium and zirconium abutment groups were 525.65 N and 514.05 N, respectively.
      No significant differences were observed between two groups regarding the
      fracture resistance levels. The maximum Von Mises equivalent stress concentrated
      on zirconium copings in both of the groups. Implant-abutment-ZrO2 coping
      combination has the potential to withstand physiological occlusal forces in the
      anterior region. Three-dimensional finite elements analysis results of the
      implant-abutment-ZrO2 coping combination is compatible with the results of
      fracture resistance.

PMID- 21904011
TI  - The effect of cost function on optimum technique of the undersomersault on
      parallel bars.
AB  - The undersomersault, or felge, to handstand on parallel bars has become an
      important skill in Men's Artistic Gymnastics as it forms the basis of many
      complex variations. To receive no deductions from the judges, the undersomersault
      must be performed without demonstrating the use of strength to achieve the final
      handstand position. Two male gymnasts each performed nine undersomersaults from
      handstand to handstand while data were recorded using an automatic motion capture
      system. The highest and lowest scoring trials of each gymnast, as determined by
      four international judges, were chosen for further analysis. Three optimization
      criteria were used to generate undersomersault technique during the swing phase
      of the skill using a computer simulation model: minimization of peak joint
      torques, minimization of horizontal velocity before release, and maximization of
      angular momentum. The techniques used by both gymnasts could be explained using
      the second optimization criterion which facilitated further skill development.
      The first optimization criterion generated a technique advocated for beginners
      where strength might be expected to be a limiting factor. The third optimization
      criterion resulted in a different type of undersomersault movement of greater
      difficulty according to the FIG Code of Points.

PMID- 21904012
TI  - Kinetic analysis of ski turns based on measured ground reaction forces.
AB  - The objective of this study was to devise a method of kinetic analysis of the
      ground reaction force that enables the durations and magnitudes of forces acting
      during the individual phases of ski turns to be described exactly. The method is
      based on a theoretical analysis of physical forces acting during the ski turn.
      Two elementary phases were defined: (1) preparing to turn (initiation) and (2)
      actual turning, during which the center of gravity of the skier-ski system moves
      along a curvilinear trajectory (steering). The starting point of the turn
      analysis is a dynamometric record of the resultant acting ground reaction force
      applied perpendicularly on the ski surface. The method was applied to six expert
      skiers. They completed a slalom course comprising five gates arranged on the fall
      line of a 26 degrees  slope at a competition speed using symmetrical carving
      turns (30 evaluated turns). A dynamometric measurement system was placed on the
      carving skis (168 cm long, radius 16 m, data were recorded at 100 Hz). MATLAB
      procedures were used to evaluate eight variables during each turn: five time
      variables and three force variables. Comparison of the turn analysis results
      between individuals showed that the method is useful for answering various
      research questions associated with ski turns.

PMID- 21904013
TI  - Qualitative bacteriology in malignant wounds--a prospective, randomized,
      clinical study to compare the effect of honey and silver dressings.
AB  - Between 5% and 10% of cancer patients develop malignant wounds. In vitro and
      some clinical studies suggest that silver- or honey-coated dressings may have an
      antibacterial effect in nonmalignant wounds, but their possible antibacterial
      effect in malignant wounds remains unknown. A prospective, randomized, single
      blind controlled clinical study was conducted to evaluate the bacteriology of
      malignant wounds and compare the effect of a honey-coated (Group A) to a silver
      coated (Group B) dressing on the qualitative bacteriology of malignant wounds.
      All wound interventions were performed by the same healthcare professional. Swab
      cultures were obtained at baseline and following a 4-week intervention and were
      evaluated without information about the patient treatment group. Of the 75
      patients with advanced cancer and malignant wounds identified, 67 (34 in group A,
      33 in group B; median age 64 years, range 47-92) consented to participate and
      completed the 4-week study. The majority were women (88%) with breast cancer
      (79%). No statistically significant differences were found between the type and
      number of different wound pathogens in the wounds during the course of the study
      or between Group A and Group B. Neither anti-neoplastic nor antibiotic treatment
      influenced the presence of wound pathogens. Staphylococci were found in 42%,
      enteric bacteria in 34%, anaerobic bacteria in 16%, Pseudomonas in 10%, and
      hemolytic streptococci in 6% of wounds at baseline; in total, 25 different
      bacterial species were identified. Sixty-one percent (61%) of wounds decreased in
      size following treatment, but no significant differences were observed between
      the type and variety of wound pathogens and whether wound size decreased.
      Although quantitative bacteriological changes may have occurred, the possible
      antibacterial effect of the honey or silver dressing could not be confirmed in
      these malignant wounds. Routine wound swabbing of malignant wounds is of little
      value and should be restricted to cases where signs of infection requiring
      antibiotic intervention are observed or where resistant organisms require special
      infection control measures.

PMID- 21904014
TI  - The effect of autologous bone marrow-derived cells on healing chronic lower
      extremity wounds: results of a randomized controlled study.
AB  - Case studies suggest that bone marrow-derived stem cells may improve chronic
      wound healing. A prospective, randomized, clinical study was conducted to compare
      the rate of healing chronic lower limb wounds in patients with diabetes mellitus
      whose wounds were treated with topically applied and locally injected bone marrow
      derived cells or whole blood (control). Of the 48 patients participating in the
      study, 25 were randomized to study treatment and 23 to control treatment. At
      baseline, no significant differences were observed between the two groups for
      patient age (average for treatment group was 54 years, 3 months; range 33 to 76
      years and for the control group 58 years, 7 months; range 28 to 69 years),
      comorbidity (82% in the treatment group and 78% in the control group had diabetes
      mellitus), ulcer history (mean duration was 14.28 months in the treatment group
      and 10.21 months in the control group; SD 0.28), or baseline area (mean was 65.32
      cm2 in the treatment group and 48.83 cm2 in the control group). After obtaining
      informed consent, all wounds were surgically debrided. Wounds of study
      participants randomized to the treatment group were injected and oversprayed with
      a total of 5 cc of autologous bone marrow-derived cells. Using a similar
      procedure, the wounds of patients randomized to the control group were injected
      with 5 cc of autologous peripheral blood. All wounds were covered with saline
      moistened gauze and cotton pads. Patients were followed for a maximum of 3
      months. The average decrease in wound area at 2 weeks was 17.4% (39.6-43.4 cm2)
      in the treatment group compared to 4.84% (41.6-42.8 cm2) in the control group.
      After 12 weeks, the average decrease in wound area was 36.4% (SD 0.48) in the
      treatment group compared to 27.32% (SD 0.32) in the control group. No adverse
      events were observed. None of the patients complained of significant pain or
      discomfort following the procedure, no wound infections occurred, and all
      patients reported resumption of normal daily activity the day after the
      procedure. The results of this study show that a single application of autologous
      bone marrow-derived cells increases the rate of healing chronic lower extremity
      wounds in the early weeks of treatment. Additional studies to elucidate the
      treatment mode of action and optimal application frequency as well as comparisons
      between this and other treatment modalities are warranted.

PMID- 21904015
TI  - Bactericidal effect of ultraviolet C (UVC), direct and filtered through
      transparent plastic, on gram-positive cocci: an in vitro study.
AB  - The prevalence of wound infections caused by multidrug-resistant (MDR) bacteria
      is increasing along with concern about widespread use of antibiotics. In vitro
      studies have shown that ultraviolet radiation, especially UVC, is both an
      effective bactericidal and antifungal. However, evidence about its bactericidal
      effect on wounds covered with transparent dressings remains inconclusive.
      Transparent dressings are used to retain moisture over the wound as part of an
      intermittent negative pressure dressing-the Limited Access Dressing (LAD)
      technique. Because this dressing is designed to remain in place for a number of
      days, an in vitro study was conducted to explore the bactericidal effect of
      direct and indirect UVR through a transparent 0.15-mm thick transparent polythene
      sheet on Gram-positive cocci. Six bacterial strains were inoculated to sheep
      blood agar (SBA) plates and exposed to direct and filtered UVC (254 nm) for 5,
      10, 15, 20, 25, and 30 seconds with one media serving as a control (no UVC
      exposure). Plates were subsequently incubated for 24 hours and bacterial growth
      observed. Each set of experiment was repeated three times. Direct UVC was shown
      to have good bactericidal effect (100% eradication of organisms inoculated) at
      durations ranging from a minimum of 5 seconds (methicillin-resistant, coagulase
      negative Staphylococcus and Streptococcus pyogenes) to a maximum of 15 seconds
      (methicillin-susceptible Staphylococcus aureus and Enterococci species). No
      bactericidal effect was observed when UVC was filtered through a 0.15-mm thick
      transparent polythene sheet. The results confirm the bactericidal effect of UVC
      in vitro and suggest that this effect can be achieved after a very short period
      of time. At the same time, film dressings appear to filter UVC. This may help
      protect skin from exposure to UVC but also limits its utility for use with the
      LAD technique. In vivo studies to evaluate the shortest effective UVC treatment
      duration and follow-up clinical studies to ascertain treatment efficacy and
      effectiveness are needed.

PMID- 21904016
TI  - The effect of collagenase on ischemic wound healing: results of an in vivo study 
      .
AB  - Many chronic wounds have a limited blood supply and contain necrotic tissue that
      must be debrided. The effect of collagenase, an enzymatic debriding agent, has
      been studied in acute but not in chronic wounds. The purpose of this in vivo
      study is to evaluate the effect of collagenase on wound healing in ischemic
      wounds. The ears of eight young New Zealand White rabbits were rendered ischemic
      by ligation of caudal and central arteries and dermal circulation
      circumferentially so both ears were perfused only by the rostral artery,
      preserving the caudal, central, and rostra veins. Three 6-mm, full-thickness
      dermal punches were made on the inner surface of both ears down to perichondrium.
      One ear on each rabbit was treated with either collagenase or petrolatum ointment
      covered with a semi-occlusive dressing; wounds on the other ear of the same
      rabbit were covered with a semi-occlusive dressing only (control). On post
      wounding day 8, wound samples were collected and processed for histological
      analysis of reepithelialization (epithelial gap, percentage healed, epithelial
      height, and epidermal area) and granulation tissue formation (peak height,
      granulation tissue distance, and area). Within-animal comparison showed no
      significant differences between the petrolatum and control wounds but epithelial
      height, epidermal area, wound peak height, and granulation tissue distance and
      area were significantly different between the collagenase and control-treated
      wounds. Between-animal comparison of petrolatum- and collagenase-covered wounds
      showed statistically significant (P <0.05) differences for the following
      outcomes: epithelial gap, percenatge healed, epithelial height, epidermal area,
      wound peak height, and granulation tissue distance and area. In this ischemic
      wound model, outcomes for most of the variables associated with healing were
      significantly better in wounds covered with collagenase and a semi-occlusive
      dressing than in the control or petrolatum group. Additional in vivo studies are
      warranted to confirm these results.

PMID- 21904017
TI  - A new in vivo test method to compare wound dressing fluid handling
      characteristics and wear time.
AB  - A refined in vivo artificial wound model utilizing artificial wound fluid (AWF)
      was developed to overcome important limitations such as adhesive-skin
      interactions, movement, pressure, shear, and varying environmental conditions in
      in vitro models. Using this model, a study with primary endpoints of wear time
      and fluid handling capacity was conducted to compare two foam dressings: a high
      performance (HPF) dressing and an adhesive dressing (AAF). A 10-cm(2) artificial
      wound bed, created using a nonstick absorbent pad, was applied to the lower back
      of 24 healthy volunteers and the tip of a 23-gauge catheter was inserted into the
      pad to administer AWF. The pad and catheter were secured in place with paper tape
      and covered with the test dressings. This model and 1.0-mL AWF infusions every 12
      hours was used to simulate highly exudating wounds. The HPF dressing absorbed 75%
      more fluid before failure and remained intact for a median of 6.1 days compared
      to 3.5 days for the AAF dressing (P <0.001, Cox proportional hazard model).
      Comparisons between dressing outcomes using this model and previously published
      in vitro results suggest the model may be valid and reliable. Studies to
      ascertain the ability of this model to predict clinical dressing performance and
      research to compare other wound outcomes that affect dressing change frequency
      and cost (eg, healing) are needed.

PMID- 21904018
TI  - Evidence-informed leg ulcer care: a cohort study comparing outcomes of
      individuals choosing nurse-led clinic or home care.
AB  - Clinicians are interested in options for delivering community-based wound care.
      Studies have largely focused on nurse clinics as an alternative to people
      receiving wound care at home. A prospective, two-arm, cohort study of individuals
      who requested and received their preference for community-based leg ulcer care
      delivered in either their home or in a nurse-led clinic was conducted to explore
      the relationship between choice of care location and health outcomes. Provision
      of care was similar-ie, care was guided by an evidence-informed protocol and a
      trained nursing team. Individual and system level outcomes were compared between
      the groups, including 3-month healing rates, 1-year ulcer recurrence rate, time
      free of ulcers, health-related quality of life (HRQL), satisfaction with care,
      and resource use. Following the baseline assessment, data were collected every 3
      months until healing occurred plus a 1-year follow-up to monitor recurrence. Of
      the 104 participants (average age 67.5 years), 56 chose home and 48 chose clinic
      based care. More than half (55%) of the participants were men, 53.8% had an ulcer
      <5 cm(2) and <6 months' duration, 84% were English-speaking, and 51.9% had a
      previous episode of ulceration. No significant sociodemographic, HRQL, or
      clinical characteristic differences were found between groups at baseline. A
      trend toward improved healing for those choosing clinic care was observed (3
      month healing rates at home were 48.1% versus clinic care 66.7%, P = 0.07) but
      neither healing outcome nor other variables, including resource utilization, were
      significantly different and post-hoc analysis revealed only 48% power to detect a
      difference in healing. The results confirm previous research indicating that the
      organization rather than the location of care is most important; however,
      observed differences in healing rates pose an important question for future
      inquiry regarding the potential impact of choice and whether the quality of care
      is standardized and delivered by the same team. The concept of providing
      individuals/families with the choice of care location warrants further research.

PMID- 21904019
TI  - Optimizing a widely used protein structure alignment measure in expected
      polynomial time.
AB  - Protein structure alignment is an important tool in many biological applications,
      such as protein evolution studies, protein structure modeling, and structure
      based, computer-aided drug design. Protein structure alignment is also one of the
      most challenging problems in computational molecular biology, due to an infinite
      number of possible spatial orientations of any two protein structures. We study
      one of the most commonly used measures of pairwise protein structure similarity,
      defined as the number of pairs of atoms in two proteins that can be superimposed
      under a predefined distance cutoff. We prove that the expected running time of a
      recently published algorithm for optimizing this (and some other, derived
      measures of protein structure similarity) is polynomial.

PMID- 21904020
TI  - Breath biomarkers in environmental health science: exploring patterns in the
      human exposome.
AB  - The human genome is the counterpart to the human exposome with respect to the
      gene * environment interaction that describes health state and outcome. The
      genome has already been sequenced and is in the process of being assessed for
      specific functionality; to similarly decode the exposome will require the
      measurement and interpretation of suites of biomarker compounds in biological
      media such as blood, breath and urine. Of these, exhaled breath provides some
      important advantages for community or population-based studies in that the supply
      is essentially unlimited, the sampling procedures are non-invasive and can be
      self-administered, and there are little, if any, infectious wastes generated. The
      main concerns are to document a variety of compounds in breath, to assess what
      compounds and concentrations are considered statistically 'normal' in the healthy
      or unremarkably exposed population, and what graphic and mathematical approaches
      can be applied to assess outlier measurements as perturbations to the healthy
      exposome. In this paper, we explore a data set of exhaled breath measurements of
      exogenous exposures to jet fuel and develop summary statistics and variable
      clustering methods to establish between-group and intrinsic within-sample
      patterns that could be used to assess the status of random subjects.

PMID- 21904021
TI  - Lack of consistent intracranial pressure pulse morphological changes during
      episodes of microdialysis lactate/pyruvate ratio increase.
AB  - Lactate/pyruvate ratio (LPR) from microdialysis is a well-established marker of
      cerebral metabolic crisis. For brain injury patients, abnormally high LPR could
      indicate cerebral ischemia or failure of O(2) uptake. However, there is a debate
      on the primary factor responsible for LPR increase. Exploiting the potential of
      using the morphology of a high temporal resolution signal such as intracranial
      pulse (ICP) to characterize cerebrovascular changes, a data analysis experiment
      is taken to test whether consistent changes in ICP pulse morphological metrics
      accompany the LPR increase. We studied 3517 h of LPR and continuous ICP data from
      19 severe traumatic brain injury patients. Our morphological clustering and
      analysis of intracranial pressure (MOCAIP) algorithm was applied to ICP pulses,
      which were matched in time to the LPR measurements, and 128 pulse morphological
      metrics were extracted. We automatically identified the episodes of LPR increases
      using a moving time window of 10-20 h. We then studied the trending patterns of
      each of the 128 ICP MOCAIP metrics within these identified periods and determined
      them to be one of the following three types: increasing, decreasing or no trend.
      A binomial test was employed to investigate whether any MOCAIP metrics show a
      consistent trend among all episodes of LPR increase per patient. Regardless of
      the selected values for different parameters of the proposed method, for the
      majority of the subjects in the study (78%), none of the ICP metrics show any
      consistent trend during the episodes of LPR increase. Even for the few subjects
      who have at least one ICP metric with a consistent trend during the LPR increase
      episodes, the number of such metrics is small and varies from subject to subject.
      Given the fact that ICP pulse morphology is influenced by the cerebral
      vasculature, our results suggest that a dominant cerebral vascular cause may be
      behind the changes in LPR when LPR trends correlate with ICP pulse morphological
      changes. However, the incidence of such correlation seems to be low.

PMID- 21904022
TI  - Validation of weighted frequency-difference EIT using a three-dimensional
      hemisphere model and phantom.
AB  - Frequency-difference (FD) electrical impedance tomography (EIT) using a weighted
      voltage difference has recently been proposed for imaging haemorrhagic stroke,
      abdominal bleeding and tumors. Although its feasibility was demonstrated through
      two-dimensional numerical simulations and phantom experiments, we should validate
      the method in three-dimensional imaging objects. At the same time, we need to
      investigate its robustness against geometrical modeling errors in boundary shapes
      and electrode positions. We performed a validation study of the weighted FD
      method through three-dimensional numerical simulations and phantom experiments.
      Adopting hemispherical models and phantoms whose admittivity distributions change
      with frequency, we investigated the performance of the method to detect an
      anomaly. We found that the simple FD method fails to detect the anomaly, whereas
      reconstructed images using the weighted FD method clearly visualize the anomaly.
      The weighted FD method is robust against modeling errors of boundary-shape
      deformations and displaced electrode positions. We also found that the method is
      capable of detecting an anomaly surrounded by a shell-shaped obstacle simulating
      the skull. We propose the weighted FD method for future studies of animal and
      human experiments.

PMID- 21904023
TI  - Non-invasive measurement of local pulse pressure by pulse wave-based ultrasound
      manometry (PWUM).
AB  - Central blood pressure (CBP) has been established as a relevant indicator of
      cardiovascular disease. Despite its significance, CBP remains particularly
      challenging to measure in standard clinical practice. The objective of this study
      is to introduce pulse wave-based ultrasound manometry (PWUM) as a simple-to-use,
      non-invasive ultrasound-based method for quantitative measurement of the central
      pulse pressure. Arterial wall displacements are estimated using radiofrequency
      ultrasound signals acquired at high frame rates and the pulse pressure waveform
      is estimated using both the distension waveform and the local pulse wave
      velocity. The method was tested on the abdominal aorta of 11 healthy subjects
      (age 35.7 +/- 16 y.o.). PWUM pulse pressure measurements were compared to those
      obtained by radial applanation tonometry using a commercial system. The average
      intra-subject variability of the pulse pressure amplitude was found to be equal
      to 4.2 mmHg, demonstrating good reproducibility of the method. Excellent
      correlation was found between the waveforms obtained by PWUM and those obtained
      by tonometry in all subjects (0.94 < r < 0.98). A significant bias of 4.7 mmHg
      was found between PWUM and tonometry. PWUM is a highly translational method that
      can be easily integrated in clinical ultrasound imaging systems. It provides an
      estimate of the pulse pressure waveform at the imaged location, and may offer
      therefore the possibility to estimate the pulse pressure at different arterial
      sites. Future developments include the validation of the method against invasive
      estimates on patients, as well as its application to other large arteries.

PMID- 21904024
TI  - Controlling cell adhesion via replication of laser micro/nano-textured surfaces
      on polymers.
AB  - The aim of this study is to investigate cell adhesion and viability on highly
      rough polymeric surfaces with gradient roughness ratios and wettabilities
      prepared by microreplication of laser micro/nano-textured Si surfaces. Negative
      replicas on polydimethylsiloxane as well as positive ones on a photocurable
      (organically modified ceramic) and a biodegradable (poly(lactide-co-glycolide))
      polymer have been successfully reproduced. The final culture substrates comprised
      from forests of micron-sized conical spikes exhibiting a range of roughness
      ratios and wettabilities, was achieved by changing the laser fluence used to
      fabricate the original template surfaces. Cell culture experiments were performed
      with the fibroblast NIH/3T3 and PC12 neuronal cell lines in order to investigate
      how these surfaces are capable of modulating different types of cellular
      responses including, viability, adhesion and morphology. The results showed a
      preferential adhesion of both cell types on the microstructured surfaces compared
      to the unstructured ones. In particular, the fibroblast NIH/3T3 cells show
      optimal adhesion for small roughness ratios, independent of the surface
      wettability and polymer type, indicating a non-monotonic dependence of cell
      adhesion on surface energy. In contrast, the PC12 cells were observed to adhere
      well to the patterned surfaces independent of the roughness ratio and
      wettability. These experimental findings are correlated with micromechanical
      measurements performed on the unstructured and replicated surfaces and discussed
      on the basis of previous observations describing the relation of cell response to
      surface energy and rigidity.

PMID- 21904025
TI  - Fabrication of tissue engineering scaffolds through solid-state foaming of
      immiscible polymer blends.
AB  - In scaffold-based tissue engineering, the fabrication process is important for
      producing suitable microstructures for seeded cells to grow and reformulate. In
      this paper, we present a new approach to scaffold fabrication by combining the
      solid-state foaming and the immiscible polymer-blending method. The proposed
      approach has the advantage of being versatile and able to create a wide range of
      pore size and porosity. The proposed method is studied with polylactic acid (PLA)
      and polystyrene (PS) blends. The interconnected porous structure was created by
      first foaming the PLA/PS blend and then extracting the PS phase. The solid-state
      foaming experiments were conducted under various conditions to achieve the
      desired pore sizes. It is shown that the PS phase of the PLA/PS blend can be
      extracted much faster in the foamed samples and the pore size of the scaffolds
      can be easily controlled with proper gas foaming parameters. The average pore
      size achieved in the foaming process ranged from 20 to 70 um. After PS
      extraction, both pore size and porosity can be further improved. For example, the
      pore size and porosity increased from 48 um and 49% to 59 um and 67%,
      respectively, after the PS extraction process. The fabricated porous scaffolds
      were used to culture human osteoblast cells. Cells grew well and gradually formed
      a fibrous structure. The combined solid-state foaming and immiscible polymer
      blending method provides a new technique for fabricating tissue-engineering
      scaffolds.

PMID- 21904026
TI  - Pico- and femtosecond laser-induced crosslinking of protein microstructures:
      evaluation of processability and bioactivity.
AB  - This study reports the pico- and femtosecond laser-induced photocrosslinking of
      protein microstructures. The capabilities of a picosecond Nd:YAG laser to promote
      multiphoton excited crosslinking of proteins were evaluated by fabricating 2D and
      3D microstructures of avidin, bovine serum albumin (BSA) and biotinylated bovine
      serum albumin (bBSA). The multiphoton absorption-induced photocrosslinking of
      proteins was demonstrated here for the first time with a non-toxic biomolecule
      flavin mononucleotide (FMN) as the photosensitizer. Sub-micrometer and micrometer
      scale structures were fabricated from several different compositions of protein
      and photosensitizer by varying the average laser power and scanning speed in
      order to determine the optimal process parameters for efficient
      photocrosslinking. In addition, the retention of ligand-binding ability of the
      crosslinked protein structures was shown by fluorescence imaging of immobilized
      biotin or streptavidin conjugated fluorescence labels. The surface topography and
      the resolution of the protein patterns fabricated with the Nd:YAG laser were
      compared to the results obtained with a femtosecond Ti:Sapphire laser. Quite
      similar grain characteristics and comparable feature sizes were achieved with
      both laser sources, which demonstrates the utility of the low-cost Nd:YAG
      microlaser for direct laser writing of protein microstructures.

PMID- 21904027
TI  - In-plate protein crystallization, in situ ligand soaking and X-ray diffraction.
AB  - X-ray crystallography is now a recognized technique for ligand screening,
      especially for fragment-based drug design. However, protein crystal handling is
      still tedious and limits further automation. An alternative method for the
      solution of crystal structures of proteins in complex with small ligands is
      proposed. Crystallization drops are directly exposed to an X-ray beam after
      cocrystallization or soaking with the desired ligands. The use of dedicated
      plates in connection with an optimal parametrization of the G-rob robot allows
      efficient data collection. Three proteins currently under study in our laboratory
      for ligand screening by X-ray crystallography were used as validation test cases.
      The protein crystals belonged to different space groups, including a challenging
      monoclinic case. The resulting diffraction data can lead to clear ligand
      recognition, including indication of alternating conformations. These results
      demonstrate a possible method for automation of ligand screening by X-ray
      crystallography.

PMID- 21904028
TI  - Sixty years from discovery to solution: crystal structure of bovine liver
      catalase form III.
AB  - The crystallization and structural characterization of bovine liver catalase
      (BLC) has been intensively studied for decades. Forms I and II of BLC have
      previously been fully characterized using single-crystal X-ray diffraction. Form
      III has previously been analyzed by electron microscopy, but owing to the
      thinness of this crystal form an X-ray crystal structure had not been determined.
      Here, the crystal structure of form III of BLC is presented in space group
      P2(1)2(1)2(1), with unit-cell parameters a = 68.7, b = 173.7, c = 186.3 A. The
      asymmetric unit is composed of the biological tetramer, which is packed in a
      tetrahedron motif with three other BLC tetramers. This higher resolution
      structure has allowed an assessment of the previously published electron
      microscopy studies.

PMID- 21904029
TI  - Inhibitor-bound structures of human pyruvate dehydrogenase kinase 4.
AB  - The mitochondrial pyruvate dehydrogenase complex (PDC) catalyzes the oxidative
      decarboxylation of pyruvate to acetyl-CoA. PDC activity is tightly regulated by
      four members of a family of pyruvate dehydrogenase kinase isoforms (PDK1-4),
      which phosphorylate and inactivate PDC. Recently, the development of specific
      inhibitors of PDK4 has become an especially important focus for the
      pharmaceutical management of diabetes and obesity. In this study, crystal
      structures of human PDK4 complexed with either AMPPNP, ADP or the inhibitor
      M77976 were determined. ADP-bound PDK4 has a slightly wider active-site cleft and
      a more disordered ATP lid compared with AMPPNP-bound PDK4, although both forms of
      PDK4 assume open conformations with a wider active-site cleft than that in the
      closed conformation of the previously reported ADP-bound PDK2 structure. M77976
      binds to the ATP-binding pocket of PDK4 and causes local conformational changes
      with complete disordering of the ATP lid. M77976 binding also leads to a large
      domain rearrangement that further expands the active-site cleft of PDK4 compared
      with the ADP- and AMPPNP-bound forms. Biochemical analyses revealed that M77976
      inhibits PDK4 with increased potency compared with the previously characterized
      PDK inhibitor radicicol. Thus, the present structures demonstrate for the first
      time the flexible and dynamic aspects of PDK4 in the open conformation and
      provide a basis for the development of novel inhibitors targeting the nucleotide
      binding pocket of PDK4.

PMID- 21904030
TI  - Location and conformation of pantothenate and its derivatives in Mycobacterium
      tuberculosis pantothenate kinase: insights into enzyme action.
AB  - Previous studies of complexes of Mycobacterium tuberculosis PanK (MtPanK) with
      nucleotide diphosphates and nonhydrolysable analogues of nucleoside triphosphates
      in the presence or the absence of pantothenate established that the enzyme has
      dual specificity for ATP and GTP, revealed the unusual movement of ligands during
      enzyme action and provided information on the effect of pantothenate on the
      location and conformation of the nucleotides at the beginning and the end of
      enzyme action. The X-ray analyses of the binary complexes of MtPanK with
      pantothenate, pantothenol and N-nonylpantothenamide reported here demonstrate
      that in the absence of nucleotide these ligands occupy, with a somewhat open
      conformation, a location similar to that occupied by phosphopantothenate in the
      'end' complexes, which differs distinctly from the location of pantothenate in
      the closed conformation in the ternary 'initiation' complexes. The conformation
      and the location of the nucleotide were also different in the initiation and end
      complexes. An invariant arginine appears to play a critical role in the movement
      of ligands that takes place during enzyme action. The work presented here
      completes the description of the locations and conformations of nucleoside
      diphosphates and triphosphates and pantothenate in different binary and ternary
      complexes, and suggests a structural rationale for the movement of ligands during
      enzyme action. The present investigation also suggests that N
      alkylpantothenamides could be phosphorylated by the enzyme in the same manner as
      pantothenate.

PMID- 21904031
TI  - Structure of trifunctional THI20 from yeast.
AB  - In a recently characterized thiamin-salvage pathway, thiamin-degradation products
      are hydrolyzed by thiaminase II, yielding 4-amino-5-hydroxymethyl-2
      methylpyrimidine (HMP). This compound is an intermediate in thiamin biosynthesis
      that, once phosphorylated by an HMP kinase, can be used to synthesize thiamin
      monophosphate. Here, the crystal structure of Saccharomyces cerevisiae THI20, a
      trifunctional enzyme containing an N-terminal HMP kinase/HMP-P kinase (ThiD-like)
      domain and a C-terminal thiaminase II (TenA-like) domain, is presented.
      Comparison to structures of the monofunctional enzymes reveals that while the
      ThiD-like dimer observed in THI20 resembles other ThiD structures, the TenA-like
      domain, which is tetrameric in all previously reported structures, forms a dimer.
      Similarly, the active site of the ThiD-like domain of THI20 is highly similar to
      other known ThiD enzymes, while the TenA-like active site shows unique features
      compared with previously structurally characterized TenAs. In addition, a survey
      of known TenA structures revealed two structural classes, both of which have
      distinct conserved features. The TenA domain of THI20 possesses some features of
      both classes, consistent with its ability to hydrolyze both thiamin and the
      thiamin-degradation product 2-methyl-4-amino-5-aminomethylpyrimidine.

PMID- 21904033
TI  - Accelerating ab initio phasing with de novo models.
AB  - Ab initio phasing is one of the remaining challenges in protein crystallography.
      Recent progress in computational structure prediction has enabled the generation
      of de novo models with high enough accuracy to solve the phase problem ab initio.
      This 'ab initio phasing with de novo models' method first generates a huge number
      of de novo models and then selects some lowest energy models to solve the phase
      problem using molecular replacement. The amount of CPU time required is huge even
      for small proteins and this has limited the utility of this method. Here, an
      approach is described that significantly reduces the computing time required to
      perform ab initio phasing with de novo models. Instead of performing molecular
      replacement after the completion of all models, molecular replacement is
      initiated during the course of each simulation. The approach principally focuses
      on avoiding the refinement of the best and the worst models and terminating the
      entire simulation early once suitable models for phasing have been obtained. In a
      benchmark data set of 20 proteins, this method is over two orders of magnitude
      faster than the conventional approach. It was observed that in most cases
      molecular-replacement solutions were determined soon after the coarse-grained
      models were turned into full-atom representations. It was also found that all
      atom refinement was hardly able to change the models sufficiently to enable
      successful molecular replacement if the coarse-grained models were not very close
      to the native structure. Therefore, it remains critical to generate good-quality
      coarse-grained models to enable subsequent all-atom refinement for successful ab
      initio phasing by molecular replacement.

PMID- 21904032
TI  - Dark progression reveals slow timescales for radiation damage between T = 180 and
      240 K.
AB  - Can radiation damage to protein crystals be 'outrun' by collecting a structural
      data set before damage is manifested? Recent experiments using ultra-intense
      pulses from a free-electron laser show that the answer is yes. Here, evidence is
      presented that significant reductions in global damage at temperatures above 200
      K may be possible using conventional X-ray sources and current or soon-to-be
      available detectors. Specifically, 'dark progression' (an increase in damage with
      time after the X-rays have been turned off) was observed at temperatures between
      180 and 240 K and on timescales from 200 to 1200 s. This allowed estimation of
      the temperature-dependent timescale for damage. The rate of dark progression is
      consistent with an Arrhenius law with an activation energy of 14 kJ mol(-1). This
      is comparable to the activation energy for the solvent-coupled diffusive damage
      processes responsible for the rapid increase in radiation sensitivity as crystals
      are warmed above the glass transition near 200 K. Analysis suggests that at T =
      300 K data-collection times of the order of 1 s (and longer at lower
      temperatures) may allow significant reductions in global radiation damage,
      facilitating structure solution on crystals with liquid solvent. No dark
      progression was observed below T = 180 K, indicating that no important damage
      process is slowed through this timescale window in this temperature range.

PMID- 21904035
TI  - Structure of a tropomyosin N-terminal fragment at 0.98 A resolution.
AB  - Tropomyosin (TM) is an elongated two-chain protein that binds along actin
      filaments. Important binding sites are localized in the N-terminus of
      tropomyosin. The structure of the N-terminus of the long muscle alpha-TM has been
      solved by both NMR and X-ray crystallography. Only the NMR structure of the N
      terminus of the short nonmuscle alpha-TM is available. Here, the crystal
      structure of the N-terminus of the short nonmuscle alpha-TM (alphaTm1bZip) at a
      resolution of 0.98 A is reported, which was solved from crystals belonging to
      space group P3(1) with unit-cell parameters a = b = 33.00, c = 52.03 A, alpha =
      beta = 90, gamma = 120 degrees . The first five N-terminal residues are flexible
      and residues 6-35 form an alpha-helical coiled coil. The overall fold and the
      secondary structure of the crystal structure of alphaTM1bZip are highly similar
      to the NMR structure and the atomic coordinates of the corresponding C(alpha)
      atoms between the two structures superimpose with a root-mean-square deviation of
      0.60 A. The crystal structure validates the NMR structure, with the positions of
      the side chains being determined precisely in our structure.

PMID- 21904034
TI  - Streptavidin and its biotin complex at atomic resolution.
AB  - Atomic resolution crystallographic studies of streptavidin and its biotin complex
      have been carried out at 1.03 and 0.95 A, respectively. The wild-type protein
      crystallized with a tetramer in the asymmetric unit, while the crystals of the
      biotin complex contained two subunits in the asymmetric unit. Comparison of the
      six subunits shows the various ways in which the protein accommodates ligand
      binding and different crystal-packing environments. Conformational variation is
      found in each of the polypeptide loops connecting the eight strands in the beta
      sandwich subunit, but the largest differences are found in the flexible binding
      loop (residues 45-52). In three of the unliganded subunits the loop is in an
      'open' conformation, while in the two subunits binding biotin, as well as in one
      of the unliganded subunits, this loop 'closes' over the biotin-binding site. The
      'closed' loop contributes to the protein's high affinity for biotin. Analysis of
      the anisotropic displacement parameters included in the crystallographic models
      is consistent with the variation found in the loop structures and the view that
      the dynamic nature of the protein structure contributes to the ability of the
      protein to bind biotin so tightly.

PMID- 21904036
TI  - Structure of RiVax: a recombinant ricin vaccine.
AB  - RiVax is a recombinant protein that is currently under clinical development as
      part of a human vaccine to protect against ricin poisoning. RiVax includes ricin
      A-chain (RTA) residues 1-267 with two intentional amino-acid substitutions, V76M
      and Y80A, aimed at reducing toxicity. Here, the crystal structure of RiVax was
      solved to 2.1 A resolution and it was shown that it is superposable with that of
      the ricin toxin A-chain from Ricinus communis with a root-mean-square deviation
      of 0.6 A over 258 C(alpha) atoms. The RiVax structure is also compared with the
      recently determined structure of another potential ricin-vaccine immunogen, RTA 1
      33/44-198 R48C/T77C. Finally, the locations and solvent-exposure of two toxin
      neutralizing B-cell epitopes were examined and it was found that these epitopes
      are within or near regions predicted to be involved in catalysis. The results
      demonstrate the composition of the RiVax clinical material and will guide ongoing
      protein-engineering strategies to develop improved immunogens.

PMID- 21904037
TI  - Structural genomics of infectious disease drug targets: the SSGCID.
AB  - The Seattle Structural Genomics Center for Infectious Disease (SSGCID) is a
      consortium of researchers at Seattle BioMed, Emerald BioStructures, the
      University of Washington and Pacific Northwest National Laboratory that was
      established to apply structural genomics approaches to drug targets from
      infectious disease organisms. The SSGCID is currently funded over a five-year
      period by the National Institute of Allergy and Infectious Diseases (NIAID) to
      determine the three-dimensional structures of 400 proteins from a variety of
      Category A, B and C pathogens. Target selection engages the infectious disease
      research and drug-therapy communities to identify drug targets, essential
      enzymes, virulence factors and vaccine candidates of biomedical relevance to
      combat infectious diseases. The protein-expression systems, purified proteins,
      ligand screens and three-dimensional structures produced by SSGCID constitute a
      valuable resource for drug-discovery research, all of which is made freely
      available to the greater scientific community. This issue of Acta
      Crystallographica Section F, entirely devoted to the work of the SSGCID, covers
      the details of the high-throughput pipeline and presents a series of structures
      from a broad array of pathogenic organisms. Here, a background is provided on the
      structural genomics of infectious disease, the essential components of the SSGCID
      pipeline are discussed and a survey of progress to date is presented.

PMID- 21904038
TI  - Gene Composer in a structural genomics environment.
AB  - The structural genomics effort at the Seattle Structural Genomics Center for
      Infectious Disease (SSGCID) requires the manipulation of large numbers of amino
      acid sequences and the underlying DNA sequences which are to be cloned into
      expression vectors. To improve efficiency in high-throughput protein structure
      determination, a database software package, Gene Composer, has been developed
      which facilitates the information-rich design of protein constructs and their
      underlying gene sequences. With its modular workflow design and numerous
      graphical user interfaces, Gene Composer enables researchers to perform all
      common bioinformatics steps used in modern structure-guided protein engineering
      and synthetic gene engineering. An example of the structure determination of H1N1
      RNA-dependent RNA polymerase PB2 subunit is given.

PMID- 21904039
TI  - Gene design, cloning and protein-expression methods for high-value targets at the
      Seattle Structural Genomics Center for Infectious Disease.
AB  - Any structural genomics endeavor, particularly ambitious ones such as the NIAID
      funded Seattle Structural Genomics Center for Infectious Disease (SSGCID) and
      Center for Structural Genomics of Infectious Disease (CSGID), face technical
      challenges at all points of the production pipeline. One salvage strategy
      employed by SSGCID is combined gene engineering and structure-guided construct
      design to overcome challenges at the levels of protein expression and protein
      crystallization. Multiple constructs of each target are cloned in parallel using
      Polymerase Incomplete Primer Extension cloning and small-scale expressions of
      these are rapidly analyzed by capillary electrophoresis. Using the methods
      reported here, which have proven particularly useful for high-value targets,
      otherwise intractable targets can be resolved.

PMID- 21904040
TI  - Immobilized metal-affinity chromatography protein-recovery screening is
      predictive of crystallographic structure success.
AB  - The recombinant expression of soluble proteins in Escherichia coli continues to
      be a major bottleneck in structural genomics. The establishment of reliable
      protocols for the performance of small-scale expression and solubility testing is
      an essential component of structural genomic pipelines. The SSGCID Protein
      Production Group at the University of Washington (UW-PPG) has developed a high
      throughput screening (HTS) protocol for the measurement of protein recovery from
      immobilized metal-affinity chromatography (IMAC) which predicts successful
      purification of hexahistidine-tagged proteins. The protocol is based on manual
      transfer of samples using multichannel pipettors and 96-well plates and does not
      depend on the use of robotic platforms. This protocol has been applied to
      evaluate the expression and solubility of more than 4000 proteins expressed in E.
      coli. The UW-PPG also screens large-scale preparations for recovery from IMAC
      prior to purification. Analysis of these results show that our low-cost non
      automated approach is a reliable method for the HTS demands typical of large
      structural genomic projects. This paper provides a detailed description of these
      protocols and statistical analysis of the SSGCID screening results. The results
      demonstrate that screening for proteins that yield high recovery after IMAC, both
      after small-scale and large-scale expression, improves the selection of proteins
      that can be successfully purified and will yield a crystal structure.

PMID- 21904041
TI  - Expression of proteins in Escherichia coli as fusions with maltose-binding
      protein to rescue non-expressed targets in a high-throughput protein-expression
      and purification pipeline.
AB  - Despite recent advances, the expression of heterologous proteins in Escherichia
      coli for crystallization remains a nontrivial challenge. The present study
      investigates the efficacy of maltose-binding protein (MBP) fusion as a general
      strategy for rescuing the expression of target proteins. From a group of sequence
      verified clones with undetectable levels of protein expression in an E. coli T7
      expression system, 95 clones representing 16 phylogenetically diverse organisms
      were selected for recloning into a chimeric expression vector with an N-terminal
      histidine-tagged MBP. PCR-amplified inserts were annealed into an identical
      ligation-independent cloning region in an MBP-fusion vector and were analyzed for
      expression and solubility by high-throughput nickel-affinity binding. This
      approach yielded detectable expression of 72% of the clones; soluble expression
      was visible in 62%. However, the solubility of most proteins was marginal to poor
      upon cleavage of the MBP tag. This study offers large-scale evidence that MBP can
      improve the soluble expression of previously non-expressing proteins from a
      variety of eukaryotic and prokaryotic organisms. While the behavior of the
      cleaved proteins was disappointing, further refinements in MBP tagging may permit
      the more widespread use of MBP-fusion proteins in crystallographic studies.

PMID- 21904042
TI  - High-throughput protein production and purification at the Seattle Structural
      Genomics Center for Infectious Disease.
AB  - The establishment of an efficient and reliable protein-purification pipeline is
      essential for the success of structural genomic projects. The SSGCID Protein
      Purification Group at the University of Washington (UW-PPG) has established a
      robust protein-purification pipeline designed to purify 400 proteins per year at
      a rate of eight purifications per week. The pipeline was implemented using two
      AKTAexplorer 100 s and four AKTAprimes to perform immobilized metal-affinity
      chromatography (IMAC) and size-exclusion chromatography. Purifications were
      completed in a period of 5 d and yielded an average of 53 mg highly purified
      protein. This paper provides a detailed description of the methods used to
      purify, characterize and store SSGCID proteins. Some of the purified proteins
      were treated with 3C protease, which was expressed and purified by UW-PPG using a
      similar protocol, to cleave non-native six-histidine tags. The cleavage was
      successful in 94% of 214 attempts. Cleaved proteins yielded 2.9% more structures
      than uncleaved six-histidine-tagged proteins. This 2.9% improvement may seem
      small, but over the course of the project the structure output from UW-PPG is
      thus predicted to increase from 260 structures to 318 structures. Therefore, the
      outlined protocol with 3C cleavage and subtractive IMAC has been shown to be a
      highly efficient method for the standardized purification of recombinant proteins
      for structure determination via X-ray crystallography.

PMID- 21904043
TI  - The Protein Maker: an automated system for high-throughput parallel purification.
AB  - The Protein Maker is an automated purification system developed by Emerald
      BioSystems for high-throughput parallel purification of proteins and antibodies.
      This instrument allows multiple load, wash and elution buffers to be used in
      parallel along independent lines for up to 24 individual samples. To demonstrate
      its utility, its use in the purification of five recombinant PB2 C-terminal
      domains from various subtypes of the influenza A virus is described. Three of
      these constructs crystallized and one diffracted X-rays to sufficient resolution
      for structure determination and deposition in the Protein Data Bank. Methods for
      screening lysis buffers for a cytochrome P450 from a pathogenic fungus prior to
      upscaling expression and purification are also described. The Protein Maker has
      become a valuable asset within the Seattle Structural Genomics Center for
      Infectious Disease (SSGCID) and hence is a potentially valuable tool for a
      variety of high-throughput protein-purification applications.

PMID- 21904044
TI  - Salvage and storage of infectious disease protein targets in the SSGCID high
      throughput crystallization pathway using microfluidics.
AB  - The MPCS Plug Maker is a microcapillary-based protein-crystallization system for
      generating diffraction-ready crystals from nanovolumes of protein.
      Crystallization screening using the Plug Maker was used as a salvage pathway for
      proteins that failed to crystallize during the initial observation period using
      the traditional sitting-drop vapor-diffusion method. Furthermore, the
      CrystalCards used to store the crystallization experiments set up by the Plug
      Maker are shown be a viable container for long-term storage of protein crystals
      without a discernable loss of diffraction quality with time. Use of the Plug
      Maker with SSGCID proteins is demonstrated to be an effective crystal-salvage and
      storage method.

PMID- 21904045
TI  - Wheat germ cell-free expression system as a pathway to improve protein yield and
      solubility for the SSGCID pipeline.
AB  - Recombinant expression of proteins of interest in Escherichia coli is an
      important tool in the determination of protein structure. However, lack of
      expression and insolubility remain significant challenges to the expression and
      crystallization of these proteins. The SSGCID program uses a wheat germ cell-free
      expression system as a rescue pathway for proteins that are either not expressed
      or insoluble when produced in E. coli. Testing indicates that the system is a
      valuable tool for these protein targets. Further increases in solubility were
      obtained by the addition of the NVoy polymer reagent to the reaction mixture.
      These data indicate that this eukaryotic cell-free expression system has a high
      success rate and that the addition of specific reagents can increase the yield of
      soluble protein.

PMID- 21904046
TI  - Structures of phosphopantetheine adenylyltransferase from Burkholderia
      pseudomallei.
AB  - Phosphopantetheine adenylyltransferase (PPAT) catalyzes the fourth of five steps
      in the coenzyme A biosynthetic pathway, reversibly transferring an adenylyl group
      from ATP onto 4'-phosphopantetheine to yield dephospho-coenzyme A and
      pyrophosphate. Burkholderia pseudomallei is a soil- and water-borne pathogenic
      bacterium and the etiologic agent of melioidosis, a potentially fatal systemic
      disease present in southeast Asia. Two crystal structures are presented of the
      PPAT from B. pseudomallei with the expectation that, because of the importance of
      the enzyme in coenzyme A biosynthesis, they will aid in the search for defenses
      against this pathogen. A crystal grown in ammonium sulfate yielded a 2.1 A
      resolution structure that contained dephospho-coenzyme A with partial occupancy.
      The overall structure and ligand-binding interactions are quite similar to other
      bacterial PPAT crystal structures. A crystal grown at low pH in the presence of
      coenzyme A yielded a 1.6 A resolution structure in the same crystal form.
      However, the experimental electron density was not reflective of fully ordered
      coenzyme A, but rather was only reflective of an ordered 4'-diphosphopantetheine
      moiety.

PMID- 21904047
TI  - Structures of a putative zeta-class glutathione S-transferase from the pathogenic
      fungus Coccidioides immitis.
AB  - Coccidioides immitis is a pathogenic fungus populating the southwestern United
      States and is a causative agent of coccidioidomycosis, sometimes referred to as
      Valley Fever. Although the genome of this fungus has been sequenced, many operons
      are not properly annotated. Crystal structures are presented for a putative
      uncharacterized protein that shares sequence similarity with zeta-class
      glutathione S-transferases (GSTs) in both apo and glutathione-bound forms. The
      apo structure reveals a nonsymmetric homodimer with each protomer comprising two
      subdomains: a C-terminal helical domain and an N-terminal thioredoxin-like domain
      that is common to all GSTs. Half-site binding is observed in the glutathione
      bound form. Considerable movement of some components of the active site relative
      to the glutathione-free form was observed, indicating an induced-fit mechanism
      for cofactor binding. The sequence homology, structure and half-site occupancy
      imply that the protein is a zeta-class glutathione S-transferase, a
      maleylacetoacetate isomerase (MAAI).

PMID- 21904048
TI  - An ensemble of structures of Burkholderia pseudomallei 2,3-bisphosphoglycerate
      dependent phosphoglycerate mutase.
AB  - Burkholderia pseudomallei is a soil-dwelling bacterium endemic to Southeast Asia
      and Northern Australia. Burkholderia is responsible for melioidosis, a serious
      infection of the skin. The enzyme 2,3-bisphosphoglycerate-dependent
      phosphoglycerate mutase (PGAM) catalyzes the interconversion of 3
      phosphoglycerate and 2-phosphoglycerate, a key step in the glycolytic pathway. As
      such it is an extensively studied enzyme and X-ray crystal structures of PGAM
      enzymes from multiple species have been elucidated. Vanadate is a phosphate mimic
      that is a powerful tool for studying enzymatic mechanisms in phosphoryl-transfer
      enzymes such as phosphoglycerate mutase. However, to date no X-ray crystal
      structures of phosphoglycerate mutase have been solved with vanadate acting as a
      substrate mimic. Here, two vanadate complexes together with an ensemble of
      substrate and fragment-bound structures that provide a comprehensive picture of
      the function of the Burkholderia enzyme are reported.

PMID- 21904049
TI  - Structure of fructose bisphosphate aldolase from Bartonella henselae bound to
      fructose 1,6-bisphosphate.
AB  - Fructose bisphosphate aldolase (FBPA) enzymes have been found in a broad range of
      eukaryotic and prokaryotic organisms. FBPA catalyses the cleavage of fructose 1,6
      bisphosphate into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. The
      SSGCID has reported several FBPA structures from pathogenic sources, including
      the bacterium Brucella melitensis and the protozoan Babesia bovis. Bioinformatic
      analysis of the Bartonella henselae genome revealed an FBPA homolog. The B.
      henselae FBPA enzyme was recombinantly expressed and purified for X-ray
      crystallographic studies. The purified enzyme crystallized in the apo form but
      failed to diffract; however, well diffracting crystals could be obtained by
      cocrystallization in the presence of the native substrate fructose 1,6
      bisphosphate. A data set to 2.35 A resolution was collected from a single crystal
      at 100 K. The crystal belonged to the orthorhombic space group P2(1)2(1)2(1),
      with unit-cell parameters a=72.39, b=127.71, c=157.63 A. The structure was
      refined to a final free R factor of 22.2%. The structure shares the typical
      barrel tertiary structure and tetrameric quaternary structure reported for
      previous FBPA structures and exhibits the same Schiff base in the active site.

PMID- 21904050
TI  - Structure of fructose bisphosphate aldolase from Encephalitozoon cuniculi.
AB  - Fructose bisphosphate aldolose (FBPA) enzymes have been found in a broad range of
      eukaryotic and prokaryotic organisms. FBPA catalyses the cleavage of fructose 1,6
      bisphosphate into glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. The
      SSGCID has reported several FBPA structures from pathogenic sources.
      Bioinformatic analysis of the genome of the eukaryotic microsporidian parasite
      Encephalitozoon cuniculi revealed an FBPA homolog. The structures of this enzyme
      in the presence of the native substrate FBP and also with the partial substrate
      analog phosphate are reported. The purified enzyme crystallized in 90 mM Bis-Tris
      propane pH 6.5, 18% PEG 3350, 18 mM NaKHPO(4), 10 mM urea for the phosphate-bound
      form and 100 mM Bis-Tris propane pH 6.5, 20% PEG 3350, 20 mM fructose 1,6
      bisphosphate for the FBP-bound form. In both cases protein was present at 25 mg
      ml(-1) and the sitting-drop vapour-diffusion method was used. For the FBP-bound
      form, a data set to 2.37 A resolution was collected from a single crystal at 100
      K. The crystal belonged to the orthorhombic space group C222(1), with unit-cell
      parameters a=121.46, b=135.82, c=61.54 A. The structure was refined to a final
      free R factor of 20.8%. For the phosphate-bound form, a data set was collected to
      2.00 A resolution. The space group was also C222(1) and the unit-cell parameters
      were a=121.96, b=137.61, c=62.23 A. The structure shares the typical barrel
      tertiary structure reported for previous FBPA structures and exhibits the same
      Schiff base in the active site. The quaternary structure is dimeric. This work
      provides a direct experimental result for the substrate-binding conformation of
      the product state of E. cuniculi FBPA.

PMID- 21904051
TI  - Probing conformational states of glutaryl-CoA dehydrogenase by fragment
      screening.
AB  - Glutaric acidemia type 1 is an inherited metabolic disorder which can cause
      macrocephaly, muscular rigidity, spastic paralysis and other progressive movement
      disorders in humans. The defects in glutaryl-CoA dehydrogenase (GCDH) associated
      with this disease are thought to increase holoenzyme instability and reduce
      cofactor binding. Here, the first structural analysis of a GCDH enzyme in the
      absence of the cofactor flavin adenine dinucleotide (FAD) is reported. The apo
      structure of GCDH from Burkholderia pseudomallei reveals a loss of secondary
      structure and increased disorder in the FAD-binding pocket relative to the
      ternary complex of the highly homologous human GCDH. After conducting a fragment
      based screen, four small molecules were identified which bind to GCDH from B.
      pseudomallei. Complex structures were determined for these fragments, which cause
      backbone and side-chain perturbations to key active-site residues. Structural
      insights from this investigation highlight differences from apo GCDH and the
      utility of small-molecular fragments as chemical probes for capturing alternative
      conformational states of preformed protein crystals.

PMID- 21904052
TI  - Inhibitor-bound complexes of dihydrofolate reductase-thymidylate synthase from
      Babesia bovis.
AB  - Babesiosis is a tick-borne disease caused by eukaryotic Babesia parasites which
      are morphologically similar to Plasmodium falciparum, the causative agent of
      malaria in humans. Like Plasmodium, different species of Babesia are tuned to
      infect different mammalian hosts, including rats, dogs, horses and cattle. Most
      species of Plasmodium and Babesia possess an essential bifunctional enzyme for
      nucleotide synthesis and folate metabolism: dihydrofolate reductase-thymidylate
      synthase. Although thymidylate synthase is highly conserved across organisms, the
      bifunctional form of this enzyme is relatively uncommon in nature. The structural
      characterization of dihydrofolate reductase-thymidylate synthase in Babesia
      bovis, the causative agent of babesiosis in livestock cattle, is reported here.
      The apo state is compared with structures that contain dUMP, NADP and two
      different antifolate inhibitors: pemetrexed and raltitrexed. The complexes reveal
      modes of binding similar to that seen in drug-resistant malaria strains and point
      to the utility of applying structural studies with proven cancer chemotherapies
      towards infectious disease research.

PMID- 21904053
TI  - Structure of a Nudix hydrolase (MutT) in the Mg(2+)-bound state from Bartonella
      henselae, the bacterium responsible for cat scratch fever.
AB  - Cat scratch fever (also known as cat scratch disease and bartonellosis) is an
      infectious disease caused by the proteobacterium Bartonella henselae following a
      cat scratch. Although the infection usually resolves spontaneously without
      treatment in healthy adults, bartonellosis may lead to severe complications in
      young children and immunocompromised patients, and there is new evidence
      suggesting that B. henselae may be associated with a broader range of clinical
      symptoms then previously believed. The genome of B. henselae contains genes for
      two putative Nudix hydrolases, BH02020 and BH01640 (KEGG). Nudix proteins play an
      important role in regulating the intracellular concentration of nucleotide
      cofactors and signaling molecules. The amino-acid sequence of BH02020 is similar
      to that of the prototypical member of the Nudix superfamily, Escherichia coli
      MutT, a protein that is best known for its ability to neutralize the promutagenic
      compound 7,8-dihydro-8-oxoguanosine triphosphate. Here, the crystal structure of
      BH02020 (Bh-MutT) in the Mg(2+)-bound state was determined at 2.1 A resolution
      (PDB entry 3hhj). As observed in all Nudix hydrolase structures, the alpha-helix
      of the highly conserved 'Nudix box' in Bh-MutT is one of two helices that
      sandwich a four-stranded mixed beta-sheet with the central two beta-strands
      parallel to each other. The catalytically essential divalent cation observed in
      the Bh-MutT structure, Mg(2+), is coordinated to the side chains of Glu57 and
      Glu61. The structure is not especially robust; a temperature melt obtained using
      circular dichroism spectroscopy shows that Bh-MutT irreversibly unfolds and
      precipitates out of solution upon heating, with a T(m) of 333 K.

PMID- 21904054
TI  - Structure of a cyclin-dependent kinase from Giardia lamblia.
AB  - Giardia lamblia is the etiologic agent of giardiasis, a water-borne infection
      that is prevalent throughout the world. The need for new therapeutics for the
      treatment of giardiasis is of paramount importance. Owing to the ubiquitous
      nature of kinases and their vital importance in organisms, they are potential
      drug targets. In this paper, the first structure of a cyclin-dependent kinase
      (CDK) from G. lamblia (GlCDK; UniProt A8BZ95) is presented. CDKs are cell-cycle
      associated kinases that are actively being pursued as targets for anticancer
      drugs as well as for antiparasitic chemotherapy. Generally, a CDK forms a complex
      with its associated cyclin. This CDK-cyclin complex is active and acts as a
      serine/threonine protein kinase. Typically, CDKs are responsible for the
      transition to the next phase of the cell cycle. Although the structure of GlCDK
      with its associated cyclin was not solved, the 1.85 A resolution structure of apo
      GlCDK and a 2.0 A resolution structure of GlCDK in complex with adenosine
      monophosphate are presented and the structural differences from the orthologous
      human CDK2 and CDK3 are discussed.

PMID- 21904055
TI  - Structure of thymidylate kinase from Ehrlichia chaffeensis.
AB  - The enzyme thymidylate kinase phosphorylates the substrate thymidine 5'-phosphate
      (dTMP) to form thymidine 5'-diphosphate (dTDP), which is further phosphorylated
      to dTTP for incorporation into DNA. Ehrlichia chaffeensis is the etiologic agent
      of human monocytotropic erlichiosis (HME), a potentially life-threatening tick
      borne infection. HME is endemic in the United States from the southern states up
      to the eastern seaboard. HME is transmitted to humans via the lone star tick
      Amblyomma americanum. Here, the 2.15 A resolution crystal structure of
      thymidylate kinase from E. chaffeensis in the apo form is presented.

PMID- 21904056
TI  - Structure of triosephosphate isomerase from Cryptosporidium parvum.
AB  - Cryptosporidium parvum is one of several Cryptosporidium spp. that cause the
      parasitic infection cryptosporidiosis. Cryptosporidiosis is a diarrheal infection
      that is spread via the fecal-oral route and is commonly caused by contaminated
      drinking water. Triosephosphate isomerase is an enzyme that is ubiquitous to all
      organisms that perform glycolysis. Triosephosphate isomerase catalyzes the
      formation of glyceraldehyde 3-phosphate from dihydroxyacetone phosphate, which is
      a critical step to ensure the maximum ATP production per glucose molecule. In
      this paper, the 1.55 A resolution crystal structure of the open-loop form of
      triosephosphate isomerase from C. parvum Iowa II is presented. An unidentified
      electron density was found in the active site.

PMID- 21904057
TI  - Structure of nitrilotriacetate monooxygenase component B from Mycobacterium
      thermoresistibile.
AB  - Mycobacterium tuberculosis belongs to a large family of soil bacteria which can
      degrade a remarkably broad range of organic compounds and utilize them as carbon,
      nitrogen and energy sources. It has been proposed that a variety of mycobacteria
      can subsist on alternative carbon sources during latency within an infected human
      host, with the help of enzymes such as nitrilotriacetate monooxygenase (NTA-Mo).
      NTA-Mo is a member of a class of enzymes which consist of two components: A and
      B. While component A has monooxygenase activity and is responsible for the
      oxidation of the substrate, component B consumes cofactor to generate reduced
      flavin mononucleotide, which is required for component A activity. NTA-MoB from
      M. thermoresistibile, a rare but infectious close relative of M. tuberculosis
      which can thrive at elevated temperatures, has been expressed, purified and
      crystallized. The 1.6 A resolution crystal structure of component B of NTA-Mo
      presented here is one of the first crystal structures determined from the
      organism M. thermoresistibile. The NTA-MoB crystal structure reveals a homodimer
      with the characteristic split-barrel motif typical of flavin reductases.
      Surprisingly, NTA-MoB from M. thermoresistibile contains a C-terminal tail that
      is highly conserved among mycobacterial orthologs and resides in the active site
      of the other protomer. Based on the structure, the C-terminal tail may modulate
      NTA-MoB activity in mycobacteria by blocking the binding of flavins and NADH.

PMID- 21904058
TI  - BrabA.11339.a: anomalous diffraction and ligand binding guide towards the
      elucidation of the function of a 'putative beta-lactamase-like protein' from
      Brucella melitensis.
AB  - The crystal structure of a beta-lactamase-like protein from Brucella melitensis
      was initially solved by SAD phasing from an in-house data set collected on a
      crystal soaked with iodide. A high-resolution data set was collected at a
      synchroton at the Se edge wavelength, which also provided an independent source
      of phasing using a small anomalous signal from metal ions in the active site.
      Comparisons of anomalous peak heights at various wavelengths allowed the
      identification of the active-site metal ions as manganese. In the native data set
      a partially occupied GMP could be identified. When co-crystallized with AMPPNP or
      GMPPNP, clear density for the hydrolyzed analogs was observed, providing hints to
      the function of the protein.

PMID- 21904059
TI  - Structure of aldose reductase from Giardia lamblia.
AB  - Giardia lamblia is an anaerobic aerotolerant eukaryotic parasite of the
      intestines. It is believed to have diverged early from eukarya during evolution
      and is thus lacking in many of the typical eukaryotic organelles and biochemical
      pathways. Most conspicuously, mitochondria and the associated machinery of
      oxidative phosphorylation are absent; instead, energy is derived from substrate
      level phosphorylation. Here, the 1.75 A resolution crystal structure of G.
      lamblia aldose reductase heterologously expressed in Escherichia coli is
      reported. As in other oxidoreductases, G. lamblia aldose reductase adopts a TIM
      barrel conformation with the NADP(+)-binding site located within the eight beta
      strands of the interior.

PMID- 21904060
TI  - Structure of 3-ketoacyl-(acyl-carrier-protein) reductase from Rickettsia
      prowazekii at 2.25 A resolution.
AB  - Rickettsia prowazekii, a parasitic Gram-negative bacterium, is in the second
      highest biodefense category of pathogens of the National Institute of Allergy and
      Infectious Diseases, but only a handful of structures have been deposited in the
      PDB for this bacterium; to date, all of these have been solved by the SSGCID.
      Owing to its small genome (about 800 protein-coding genes), it relies on the host
      for many basic biosynthetic processes, hindering the identification of potential
      antipathogenic drug targets. However, like many bacteria and plants, its
      metabolism does depend upon the type II fatty-acid synthesis (FAS) pathway for
      lipogenesis, whereas the predominant form of fatty-acid biosynthesis in humans is
      via the type I pathway. Here, the structure of the third enzyme in the FAS
      pathway, 3-ketoacyl-(acyl-carrier-protein) reductase, is reported at a resolution
      of 2.25 A. Its fold is highly similar to those of the existing structures from
      some well characterized pathogens, such as Mycobacterium tuberculosis and
      Burkholderia pseudomallei, but differs significantly from the analogous mammalian
      structure. Hence, drugs known to target the enzymes of pathogenic bacteria may
      serve as potential leads against Rickettsia, which is responsible for spotted
      fever and typhus and is found throughout the world.

PMID- 21904061
TI  - Structure of fumarate hydratase from Rickettsia prowazekii, the agent of typhus
      and suspected relative of the mitochondria.
AB  - Rickettsiae are obligate intracellular parasites of eukaryotic cells that are the
      causative agents responsible for spotted fever and typhus. Their small genome
      (about 800 protein-coding genes) is highly conserved across species and has been
      postulated as the ancestor of the mitochondria. No genes that are required for
      glycolysis are found in the Rickettsia prowazekii or mitochondrial genomes, but a
      complete set of genes encoding components of the tricarboxylic acid cycle and the
      respiratory-chain complex is found in both. A 2.4 A resolution crystal structure
      of R. prowazekii fumarate hydratase, an enzyme catalyzing the third step of the
      tricarboxylic acid cycle pathway that ultimately converts phosphoenolpyruvate
      into succinyl-CoA, has been solved. A structure alignment with human
      mitochondrial fumarate hydratase highlights the close similarity between R.
      prowazekii and mitochondrial enzymes.

PMID- 21904062
TI  - Solution structure of an arsenate reductase-related protein, YffB, from Brucella
      melitensis, the etiological agent responsible for brucellosis.
AB  - Brucella melitensis is the etiological agent responsible for brucellosis. Present
      in the B. melitensis genome is a 116-residue protein related to arsenate
      reductases (Bm-YffB; BR0369). Arsenate reductases (ArsC) convert arsenate ion
      (H(2)AsO(4)(-)), a compound that is toxic to bacteria, to arsenite ion (AsO(2)(
      )), a product that may be efficiently exported out of the cell. Consequently, Bm
      YffB is a potential drug target because if arsenate reduction is the protein's
      major biological function then disabling the cell's ability to reduce arsenate
      would make these cells more sensitive to the deleterious effects of arsenate.
      Size-exclusion chromatography and NMR spectroscopy indicate that Bm-YffB is a
      monomer in solution. The solution structure of Bm-YffB (PDB entry 2kok) shows
      that the protein consists of two domains: a four-stranded mixed beta-sheet
      flanked by two alpha-helices on one side and an alpha-helical bundle. The
      alpha/beta domain is characteristic of the fold of thioredoxin-like proteins and
      the overall structure is generally similar to those of known arsenate reductases
      despite the marginal sequence similarity. Chemical shift perturbation studies
      with (15)N-labeled Bm-YffB show that the protein binds reduced glutathione at a
      site adjacent to a region similar to the HX(3)CX(3)R catalytic sequence motif
      that is important for arsenic detoxification activity in the classical arsenate
      reductase family of proteins. The latter observation supports the hypothesis that
      the ArsC-YffB family of proteins may function as glutathione-dependent thiol
      reductases. However, comparison of the structure of Bm-YffB with the structures
      of proteins from the classical ArsC family suggest that the mechanism and
      possibly the function of Bm-YffB and other related proteins (ArsC-YffB) may
      differ from those of the ArsC family of proteins.

PMID- 21904063
TI  - NMR structure of an acyl-carrier protein from Borrelia burgdorferi.
AB  - Nearly complete resonance assignment and the high-resolution NMR structure of the
      acyl-carrier protein from Borrelia burgdorferi, a target of the Seattle
      Structural Genomics Center for Infectious Disease (SSGCID) structure
      determination pipeline, are reported. This protein was chosen as a potential
      target for drug-discovery efforts because of its involvement in fatty-acid
      biosynthesis, an essential metabolic pathway, in bacteria. It was possible to
      assign >98% of backbone resonances and >92% of side-chain resonances using
      multidimensional NMR spectroscopy. The NMR structure was determined to a backbone
      r.m.s.d. of 0.4 A and contained four alpha-helices and two 3(10)-helices. A
      structure-homology search revealed that this protein is highly similar to the
      acyl-carrier protein from Aquifex aeolicus.

PMID- 21904064
TI  - Comparative analysis of glutaredoxin domains from bacterial opportunistic
      pathogens.
AB  - Glutaredoxin proteins (GLXRs) are essential components of the glutathione system
      that reductively detoxify substances such as arsenic and peroxides and are
      important in the synthesis of DNA via ribonucleotide reductases. NMR solution
      structures of glutaredoxin domains from two Gram-negative opportunistic
      pathogens, Brucella melitensis and Bartonella henselae, are presented. These
      domains lack the N-terminal helix that is frequently present in eukaryotic GLXRs.
      The conserved active-site cysteines adopt canonical proline/tyrosine-stabilized
      geometries. A difference in the angle of alpha-helix 2 relative to the beta-sheet
      surface and the presence of an extended loop in the human sequence suggests
      potential regulatory regions and/or protein-protein interaction motifs. This
      observation is consistent with mutations in this region that suppress defects in
      GLXR-ribonucleotide reductase interactions. These differences between the human
      and bacterial forms are adjacent to the dithiol active site and may permit
      species-selective drug design.

PMID- 21904065
TI  - Solution-state NMR structure and biophysical characterization of zinc-substituted
      rubredoxin B (Rv3250c) from Mycobacterium tuberculosis.
AB  - Owing to the evolution of multi-drug-resistant and extremely drug-resistant
      Mycobacterium tuberculosis strains, there is an urgent need to develop new
      antituberculosis strategies to prevent TB epidemics in the industrial world.
      Among the potential new drug targets are two small nonheme iron-binding proteins,
      rubredoxin A (Rv3251c) and rubredoxin B (Rv3250c), which are believed to play a
      role in electron-transfer processes. Here, the solution structure and biophysical
      properties of one of these two proteins, rubredoxin B (Mt-RubB), determined in
      the zinc-substituted form are reported. The zinc-substituted protein was prepared
      by expressing Mt-RubB in minimal medium containing excess zinc acetate. Size
      exclusion chromatography and NMR spectroscopy indicated that Mt-RubB was a
      monomer in solution. The structure (PDB entry 2kn9) was generally similar to
      those of other rubredoxins, containing a three-stranded antiparallel beta-sheet
      (beta2-beta1-beta3) and a metal tetrahedrally coordinated to the S atoms of four
      cysteine residues (Cys9, Cys12, Cys42 and Cys45). The first pair of cysteine
      residues is at the C-terminal end of the first beta-strand and the second pair of
      cysteine residues is towards the C-terminal end of the loop between beta2 and
      beta3. The structure shows the metal buried deeply within the protein, an
      observation that is supported by the inability to remove the metal with excess
      EDTA at room temperature. Circular dichroism spectroscopy shows that this
      stability extends to high temperature, with essentially no change being observed
      in the CD spectrum of Mt-RubB upon heating to 353 K.

PMID- 21904066
TI  - Structure of the cystathionine gamma-synthase MetB from Mycobacterium ulcerans.
AB  - Cystathionine gamma-synthase (CGS) is a transulfurication enzyme that catalyzes
      the first specific step in L-methionine biosynthesis by the reaction of O(4)
      succinyl-L-homoserine and L-cysteine to produce L-cystathionine and succinate.
      Controlling the first step in L-methionine biosythesis, CGS is an excellent
      potential drug target. Mycobacterium ulcerans is a slow-growing mycobacterium
      that is the third most common form of mycobacterial infection, mainly infecting
      people in Africa, Australia and Southeast Asia. Infected patients display a
      variety of skin ailments ranging from indolent non-ulcerated lesions as well as
      ulcerated lesions. Here, the crystal structure of CGS from M. ulcerans covalently
      linked to the cofactor pyridoxal phosphate (PLP) is reported at 1.9 A resolution.
      A second structure contains PLP as well as a highly ordered HEPES molecule in the
      active site acting as a pseudo-ligand. These results present the first structure
      of a CGS from a mycobacterium and allow comparison with other CGS enzymes. This
      is also the first structure reported from the pathogen M. ulcerans.

PMID- 21904067
TI  - Pain in pancreatic cancer: does drug treatment still play a role?

PMID- 21904068
TI  - Resection status, age and nodal involvement determine survival among patients
      receiving adjuvant chemoradiotherapy in pancreatic adenocarcinoma.
AB  - CONTEXT: Pancreas cancer can potentially be cured by resection, but the role of
      adjuvant chemotherapy and/or chemoradiation has been controversial. OBJECTIVES:
      To better define clinicopathological factors that may serve as predictive and/or
      prognostic variables. PATIENTS: Between 1984 and 2006, we retrospectively
      analyzed 91 patients with pancreas cancer treated with pancreaticoduodenectomy or
      total pancreatectomy followed by adjuvant 5-fluorouracil-based chemoradiation at
      the University of Pennsylvania. Final pathological coding including margin status
      was confirmed by a pathologist. INTERVENTIONS: Patients were treated with 48.6 to
      63.0 Gy, and 96.7% completed their prescribed radiation dose. MAIN OUTCOME
      MEASURES: The prognostic significance of demographic factors, stage, year of
      surgery, tumor location, grade, resection status, and number of positive lymph
      nodes on overall survival were examined. RESULTS: With a median follow-up of 6.5
      years, the overall median survival was 2.3 years (95% CI 1.5-3.2 years), and the
      5-year overall survival was 28.9%. In multivariate analysis, completeness of
      resection (P<0.001), fewer number of positive lymph nodes (0 vs. 1-2 vs. 3 or
      more) (P=0.004), and age less than, or equal to, 60 years (P=0.006) were all
      independently associated with improved overall survival. The overall survival
      reported in this study compares favorably with the results of other single
      institution studies and with the RTOG 97-04 trial. CONCLUSIONS: Adjuvant 5-FU
      based chemoradiation following radical pancreatectomy can be delivered safely and
      results in comparatively good overall survival. The results of this analysis
      underscore the importance of resection status, number of involved lymph nodes and
      patient age as prognostic characteristics. These factors may be considered
      stratification variables for future post-pancreatectomy adjuvant therapy trials.

PMID- 21904069
TI  - Spleen-preserving distal pancreatectomy with resection of the splenic vessels.
      Should one rely on the short gastric arteries?
AB  - CONTEXT: Knowing the collaterals is essential for a spleen-preserving distal
      pancreatectomy with resection of the splenic vessels. OBJECTIVE: To ascertain the
      sources of the blood supply to the spleen after a spleen-preserving distal
      pancreatectomy with resection of the splenic vessels. METHODS: Perfusion of the
      cadaveric left gastric and right gastroepiploic arteries with methylene blue
      after occlusion of all the arteries except the short gastric arteries (n=10).
      Intraoperative color Doppler ultrasound was used for the evaluation of the hilar
      arterial blood flow at distal pancreatectomy (n=23) after 1) clamping of the
      splenic artery alone, 2) clamping of the splenic and left gastroepiploic arteries
      and 3) clamping of the splenic and short gastric arteries. CT angiography of the
      gastric and splenic vessels before and after a spleen-preserving distal
      pancreatectomy (n=10). RESULTS: Perfusion of the cadaveric arteries revealed no
      effective direct or indirect (through the submucous gastric arterial network)
      communication between the left gastric and the branches of the short gastric
      arteries. In no case did intraoperative color Doppler ultrasound detect any hilar
      arterial blood flow after the clamping of the splenic and left gastroepiploic
      arteries. The clamping of the short gastric arteries did not change the flow
      parameters. In none of the cases did a post-spleen-preserving distal
      pancreatectomy with resection of the splenic vessels CT angiography delineate the
      short gastric vessels supplying the spleen. In all cases, the gastroepiploic
      arcade was the main arterial pathway feeding the spleen. CONCLUSION:
      Experimental, intra- and postoperative instrumental investigations did not show
      the short gastric arteries to be engaged in the blood supply to the spleen after
      a spleen-preserving distal pancreatectomy with resection of the splenic vessels.
      In all cases, the left gastroepiploic artery was the main collateral vessel.

PMID- 21904071
TI  - Successful diagnosis and management of biliary cast syndrome in a liver
      transplant patient using single operator cholangioscopy.
AB  - CONTEXT: Biliary cast syndrome is an unusual complication of orthotopic liver
      transplantation with serious clinical implications. Surgical management has been
      the mainstay of treatment. Endoscopic techniques are recently described in the
      successful removal of biliary casts. Peroral single operator cholangioscopy is
      useful for direct visualization of bile ducts, tissue sampling and therapeutic
      applications. CASE REPORT: We report here a post liver transplant patient who
      underwent successful complete endoscopic removal of biliary cast using single
      operator cholangioscopy in a single sitting. CONCLUSION: Single operator
      cholangioscopy provides a safe means of diagnosing and treating patients with
      biliary cast syndrome.

PMID- 21904070
TI  - Heterotopic pancreas of the gallbladder associated with chronic cholecystitis and
      high levels of amylasuria.
AB  - CONTEXT: Heterotopic pancreas of the gallbladder is an extremely rare entity,
      especially when pancreatic tissue appears histologically with an exclusively
      exocrine structure. CASE REPORT: We report the case of a 35-year-old man who
      presented with symptoms of acalculous gallbladder disease with high levels of
      amylasuria. Immunohistochemical analysis of the surgical specimen of the
      cholecystectomy revealed pancreatic tissue at the gallbladder wall. CONCLUSIONS:
      Heterotopic pancreatic tissue is a rare pathological finding in the gallbladder.
      It requires consideration and sensitization in the differential diagnosis of
      acalculous gallbladder disease, which can explain hyperamylasuria in cases of
      unknown origin.

PMID- 21904072
TI  - A minute pancreatic ductal adenocarcinoma with lipomatous pseudohypertrophy of
      the pancreas.
AB  - CONTEXT: This report describes a minute pancreatic ductal adenocarcinoma which
      appeared to be in early stage tumor progression based on the study of its
      molecular abnormalities. In addition, it was associated with lipomatous
      pseudohypertrophy, a rare disease. CASE REPORT: A 78-year-old male presented to
      our department with an incidental pancreatic tumor. Abdominal dynamic computed
      tomography showed an enlarged pancreas, and diffuse fat density in the entire
      pancreas was demonstrated. In the pancreatic body, a slightly enhanced early
      phase 10 mm mass was detected. He underwent a distal pancreatectomy. The
      histological features of the tumor revealed abundant fibrosis and duct lesions
      with various atypia. Duct lesions equivalent to well-differentiated
      adenocarcinoma were shown sparsely, but no vessel or lymphatic permeation nor
      perineural invasion were observed. In the background of the pancreas, diffuse
      fatty infiltrations which were composed of abundant normal adipose tissue and
      scattered pancreatic parenchyma were observed. The results of immunolabeling for
      MUC1, p16, p53 and Smad4 demonstrated that there is the possibility of
      coexistence of precancerous duct lesions and cancerous lesions in the genetic
      progression of pancreatic cancer. CONCLUSION: The above results suggested that
      this pancreatic ductal adenocarcinoma with lipomatous pseudohypertrophy might be
      an example of very early stage tumor progression.

PMID- 21904073
TI  - Hemosuccus pancreaticus associated with severe acute pancreatitis and
      pseudoaneurysms: a report of two cases.
AB  - CONTEXT: Hemosuccus pancreaticus is a rare cause of upper gastrointestinal
      hemorrhage. The intensity of bleeding ranges from intermittent occult bleeding to
      massive acute bleeding leading to death. Although most cases can be managed by
      angioembolization, surgery plays an important role. CASE REPORT: We report two
      cases of hemosuccus pancreaticus managed at our institution in the past three
      years. Both cases occurred associated with acute pancreatitis. A pseudocyst was
      found in one case. Angioembolization failed in one case and was not tried in the
      other because of hemodynamic instability. Both cases were successfully managed by
      surgery. CONCLUSION: Timely intervention, either by embolization or by surgery,
      can control this potentially life-threatening bleeding. Choice of treatment,
      surgery or embolization, depends on technological availability and expertise of
      the practitioner.

PMID- 21904074
TI  - Cystic pancreatic lymphangioma. The first report of a preoperative pathological
      diagnosis by endoscopic ultrasound-guided cyst aspiration.
AB  - CONTEXT: We describe a case of cystic lymphangioma of the pancreas in which a
      preoperative tissue diagnosis was made with endoscopic ultrasound-guided fine
      needle aspiration (EUS-FNA). CASE REPORT: A 20-year-old female presented with
      upper abdominal pain of two months duration and was found to have a cystic lesion
      in the pancreatic tail. Radiological imaging could not determine the organ of
      origin or the nature of the lesion. On EUS examination, a mixed micro-macrocystic
      lesion with thin delicate septae, and clear anechoic contents was found in the
      pancreatic tail. EUS-guided aspiration demonstrated the typical endothelial lined
      cystic channels. The diagnosis was confirmed after surgical resection.
      CONCLUSION: Cystic lymphangioma should be considered in the differential
      diagnosis of cystic pancreatic lesions in which the morphology is difficult to
      characterize. EUS-FNA has the potential of rendering a positive diagnosis of this
      benign entity.

PMID- 21904075
TI  - Diffuse pancreatic lesion mimicking autoimmune pancreatitis in an HIV-infected
      patient: successful treatment by antiretroviral therapy.
AB  - CONTEXT: Pancreatitis is a common complication of acquired immunodeficiency
      syndrome. The most common causes of acute pancreatitis in an HIV population are
      medication and opportunistic infections. CASE REPORT: We report the case of a
      young, untreated, HIV-infected female who presented with acute pancreatitis of
      unknown origin. Unique to this case are the autoimmune pancreatitis-like features
      on imaging studies associated with renal mass-like lesions and lymph node
      involvement as well as the favorable outcome using highly active antiretroviral
      therapy alone. CONCLUSION: In HIV-infected patients, acute pancreatitis may
      present on imaging studies as autoimmune pancreatitis. In patients with
      uncontrolled HIV infection and imaging studies suggestive of autoimmune
      pancreatitis, direct HIV-related inflammation should be considered after
      exclusion of all other causes of pancreatitis.

PMID- 21904076
TI  - Severe impaired deambulation in a patient with vitamin D and mineral deficiency
      due to exocrine pancreatic insufficiency.
AB  - CONTEXT: Skeletal muscle weakness and impaired gait function are common risk
      factors for disease and even death. Therefore, identification of the modifiable
      causes of skeletal muscle weakness should have high priority. Knowledge regarding
      optimal vitamin D treatment in cases of pancreatic insufficiency is scarce. CASE
      REPORT: We report a case of a slow decrease in ability to walk distances more
      than 100 m during the previous 6 months. Low exocrine pancreatic function
      resulting in phosphorus, magnesium and vitamin D deficiency was found. Medical
      treatment with peroral pancreatic enzymes, phosphorus, magnesium and i.m.
      injections of ergocalciferol (vitamin D2) was initiated. Gait function gradually
      increased to a walking distance of 1,500-3,000 m along with the normalization of
      the vitamin D and mineral blood levels. CONCLUSIONS: Vitamin D deficiency due to
      exocrine pancreatic insufficiency should be kept in mind as one of the reasons
      for impaired gait and skeletal muscle weakness.

PMID- 21904077
TI  - Chronic calcific pancreatitis presenting as an isolated left perinephric abscess:
      a case report and review of the literature.
AB  - CONTEXT: Acute and chronic pancreatitis may present with pseudocysts in atypical
      locations. Activated pancreatic enzymes track along anatomic fascial planes
      causing digestion of the surrounding tissues and resulting in distant
      pseudocysts. Pseudocysts at atypical locations pose significant diagnostic as
      well as therapeutic challenges. CASE REPORT: We report an unusual presentation of
      a pancreatic pseudocyst in a young male who presented with a left perinephric
      abscess. Percutaneous drainage was not successful in resolving the abscess and he
      was subsequently diagnosed as having chronic pancreatitis together with a left
      perinephric abscess. Needle knife sphincterotomy of the ampulla of Vater resulted
      in the gradual resolution of the abscess. CONCLUSION: We report a rare
      presentation of chronic pancreatitis with a perinephric abscess and its non
      surgical management. This case report indicates that any patient presenting with
      a perinephric abscess of unknown etiology not responding to conventional
      treatment modalities should be investigated for underlying pancreatitis.

PMID- 21904078
TI  - Pancreatic leak after endoscopic ultrasound guided fine needle aspiration managed
      by transpapillary pancreatic duct stenting.
AB  - CONTEXT: Endoscopic ultrasonography guided fine needle aspiration (EUS-FNA) is a
      front line test used for the diagnosis of solid as well as cystic lesions of the
      pancreas. This procedure is fairly well tolerated and associated with minimal
      complications. Local complications such as perforation and pancreatitis have been
      reported with EUS-FNA, albeit rarely. Although pancreatic duct injury can occur
      during EUS-FNA, symptomatic pancreatic duct leak as a complication of this
      procedure has never been reported. CASE REPORT: We present a 67-year-old patient
      who developed symptomatic ascites after EUS-FNA of a pancreatic neck lesion that
      required several paracenteses. Analysis of the ascitic fluid revealed that the
      fluid amylase and lipase levels were very high consistent with pancreatic
      ascites. An endoscopic retrograde pancreatography was subsequently performed that
      documented the presence of a pancreatic duct leak in the neck. The pancreatic
      duct leak and the ascites resolved after placing a pancreatic duct stent.
      CONCLUSION: A clinically significant pancreatic leak can occur as a rare
      complication of EUS-FNA that can be effectively managed by endoscopic retrograde
      pancreatography and placement of a transpapillary pancreatic duct stent.

PMID- 21904079
TI  - Posterior approach pancreaticoduodenectomy: does it really improve long-term
      survival in pancreatic head cancer?

PMID- 21904081
TI  - Early treatment of acute pancreatitis: do not forget the need for water.

PMID- 21904082
TI  - Preliminary reliability and validity of a new time-sensitive ADHD symptom scale
      in adolescents with ADHD.
AB  - OBJECTIVES: To validate the Time-Sensitive ADHD Symptom Scale (TASS) in the
      assessment of symptom change during the day in adolescents with attention
      deficit/hyperactivity disorder (ADHD). METHODS: A total of 40 participants with
      ADHD aged 13 to 17 years completed 1 or 2 visits, 1 to 9 weeks apart. The TASS
      and the ADHD Rating Scale-IV (ADHD-RS-IV) were completed twice at each visit: at
      the time of the clinic visit (in-clinic assessment) and 2 to 6 hours afterwards
      (evening assessment). RESULTS: Internal consistency of the TASS was high, with
      Cronbach's alpha coefficients of 0.91 (in-clinic) and 0.90 (evening) for visit 1,
      and 0.88 (in-clinic) and 0.86 (evening) for visit 2. Pearson's correlation
      coefficients between the TASS and ADHD-RS-IV were significant at both visits (P <
      0.0001). Stability analyses of the TASS found no significant effect between
      ratings performed at different visits (P = 0.936), but there was a significant
      effect of the assessment time within visits (P < 0.0001). There was not a
      significant visit by assessment time interaction (P = 0.924). CONCLUSIONS: The
      TASS showed high internal consistency and high concurrent validity with the ADHD
      RS-IV. Results of this preliminary study indicate that the TASS is a valid and
      reliable self-report scale for adolescents with ADHD.

PMID- 21904083
TI  - Managing ADHD across the lifespan in the primary care setting.
AB  - Attention-deficit/hyperactivity disorder (ADHD) is a chronic neurobehavioral
      condition that affects most patients throughout their lives and is associated
      with occupational underachievement, psychiatric comorbidity, and substance abuse.
      Primary care physicians (PCPs) are at the forefront of helping patients with ADHD
      manage symptoms and overcome functional impairments. In this article, the
      problems of recognizing and effectively managing ADHD are explored through the
      presentation of 2 composite patient cases based on real patients in the authors'
      practices. Both cases highlight maturational changes in ADHD-related problems as
      patients develop through childhood, adolescence, and into adulthood. The striking
      differences between the cases serve to illustrate the highly varied clinical
      presentation and developmental trajectories of ADHD, moderated by family
      environment, patient characteristics, and life events. Emphasis is placed on
      understanding the crucial developmental turning points from early childhood
      through adulthood at which patients with ADHD are most likely to need increased
      support and specialized behavioral interventions. Diagnosis of adult ADHD is also
      reviewed, including an overview of potentially clinically relevant patient
      characteristics that should alert PCPs to the possible presence of ADHD and use
      of the World Health Organization's rapid 6-item adult ADHD Self-Report Scale as a
      screening device. The present discussion challenges PCPs to recognize the varied
      presentations of what ADHD "looks like," and describes the need for PCPs to
      establish and maintain working partnerships with families, patients, and mental
      health care professionals in their local communities to successfully treat ADHD
      across the lifespan.

PMID- 21904084
TI  - Exploring the impact of once-daily OROS(r) methylphenidate (MPH) on symptoms and
      quality of life in children and adolescents with ADHD transitioning from
      immediate-release MPH.
AB  - OBJECTIVES: To explore the clinical and health-related quality of life (HRQoL)
      outcomes in children/adolescents with attention-deficit/hyperactivity disorder
      (ADHD) who required a therapy switch from immediate-release (IR) methylphenidate
      (MPH) and were initiated on Osmotic Release Oral System (OROS((r))) MPH. METHODS:
      Prospective, noninterventional study including patients (aged 6-18 years) with a
      confirmed diagnosis of ADHD who transitioned from IR MPH to OROS((r)) MPH based
      on medical needs. Patients were transitioned to OROS((r)) MPH and were followed
      for 12 weeks. Attention-deficit/hyperactivity disorder symptoms, functional
      outcomes, HRQoL, and tolerability were assessed throughout the study. RESULTS:
      598 patients entered the intention-to-treat analysis. The mean OROS((r)) MPH
      starting dose was 29.5 +/- 12.0 mg/day, increasing slightly to 33.5 +/- 13.2
      mg/day at final visit. Compared with baseline, there were significant (all P <
      0.0001) symptomatic, functional, and HRQoL improvements after transitioning from
      IR MPH to OROS((r)) MPH as assessed by the Conners' Parent Rating Scale (from
      29.0 +/- 10.5 to 19.5 +/- 11.1), Children's Global Assessment Scale (by 11.0 +/-
      13.3), and Inventory for Assessing Quality of Life (ILC) LQ0-28 scores (parents'
      rating from 17.2 +/- 3.9 to 19.4 +/- 4.0; patients' rating from 18.7 +/- 4.0 to
      20.5 +/- 3.9). Overall, no significant changes in quality of sleep or appetite
      were observed. More than 70% of parents and physicians rated the effectiveness of
      OROS((r)) MPH as at least "good" and were at least "satisfied" with OROS((r))
      MPH. The most common treatment-emergent adverse events were insomnia and
      anorexia. No clinically relevant changes in body weight or vital signs were
      observed. CONCLUSIONS: In this naturalistic setting, transitioning from IR MPH to
      OROS((r)) MPH, in patients who showed previously insufficient response and/or
      poor tolerability, was successful. Patients' and parents' HRQoL as well as burden
      of disease showed a clinically relevant improvement. OROS((r)) MPH was generally
      safe and well tolerated.

PMID- 21904086
TI  - Toward defining deficient emotional self-regulation in children with attention
      deficit/hyperactivity disorder using the Child Behavior Checklist: a controlled
      study.
AB  - OBJECTIVE: Deficient emotional self-regulation (DESR) is characterized by
      deficits in self-regulating the physiological arousal caused by strong emotions.
      We examined whether a unique profile of the Child Behavior Checklist (CBCL) would
      help identify DESR in children with attention-deficit/hyperactivity disorder
      (ADHD). METHODS: Subjects included 197 children with ADHD and 224 children
      without ADHD. We defined DESR if a child had an aggregate cut-off score of > 180
      but < 210 on the Anxiety/Depression, Aggression, and Attention scales of the CBCL
      (CBCL-DESR). This profile was selected because of: 1) its conceptual congruence
      with the clinical concept of DESR; and 2) because its extreme (> 210) form has
      been previously associated with severe forms of mood and behavioral dysregulation
      in children with ADHD. All subjects were comprehensively assessed with structured
      diagnostic interviews and a wide range of functional measures. RESULTS: Forty
      four percent of children with ADHD had a positive CBCL-DESR profile versus 2% of
      controls (P < 0.001). The CBCL-DESR profile was associated with elevated rates of
      anxiety and disruptive behavior disorders, as well as significantly more
      impairments in emotional and interpersonal functioning. CONCLUSIONS: The CBCL
      DESR profile helped identify a subgroup of children with ADHD who had a
      psychopathological and functional profile consistent with the clinical concept of
      DESR.

PMID- 21904087
TI  - A physician's guide to helping patients with ADHD find success in the workplace.
AB  - The impact of untreated adult attention-deficit/hyperactivity disorder (ADHD) in
      the workplace can be substantial, and employees with ADHD often confront
      frustration, employer disappointment, and low performance ratings. As a result,
      adults with ADHD may seek treatment from primary care providers to improve
      occupational performance. Previously considered a behavior disorder primarily
      affecting children and adolescents, ADHD in adulthood presents primarily as a
      cognitive disorder. Self-management deficits play a greater role in adult ADHD,
      particularly with respect to occupational and interpersonal functioning. Although
      specialized resources are available to assist adults with ADHD, many afflicted
      individuals may be unaware or unable to access them. Primary care providers who
      may be treating adults with ADHD are in a unique position to help them obtain the
      care and support needed to build appropriate skills and manage occupational
      issues. In this review, a literature search of the past 10 years was conducted to
      identify articles concerning ADHD and its impact on individuals in the workplace.
      The influence of ADHD on occupational functioning is discussed in the context of
      self-management impairments, diagnosis and assessment, and management strategies.
      With early and successful intervention, adults with ADHD may be able to become
      more aware of the impact of ADHD on work performance and achieve successful
      occupational experiences.

PMID- 21904085
TI  - Attention-deficit/hyperactivity disorder: is it time to reappraise the role of
      sugar consumption?
AB  - Attention-deficit/hyperactivity disorder (ADHD) affects nearly 10% of children in
      the United States, and the prevalence of this disorder has increased steadily
      over the past decades. The cause of ADHD is unknown, although recent studies
      suggest that it may be associated with a disruption in dopamine signaling whereby
      dopamine D2 receptors are reduced in reward-related brain regions. This same
      pattern of reduced dopamine-mediated signaling is observed in various reward
      deficiency syndromes associated with food or drug addiction, as well as in
      obesity. While genetic mechanisms are likely contributory to cases of ADHD, the
      marked frequency of the disorder suggests that other factors are involved in the
      etiology. In this article, we revisit the hypothesis that excessive sugar intake
      may have an underlying role in ADHD. We review preclinical and clinical data
      suggesting overlaps among ADHD, sugar and drug addiction, and obesity. Further,
      we present the hypothesis that the chronic effects of excessive sugar intake may
      lead to alterations in mesolimbic dopamine signaling, which could contribute to
      the symptoms associated with ADHD. We recommend further studies to investigate
      the possible relationship between chronic sugar intake and ADHD.

PMID- 21904088
TI  - Medication adherence and symptom reduction in adults treated with mixed
      amphetamine salts in a randomized crossover study.
AB  - OBJECTIVES: The study objectives were to 1) evaluate medication adherence for
      adults with attention-deficit/hyperactivity disorder (ADHD) treated with 3 times
      daily (TID) mixed amphetamine salts immediate release (MAS IR) versus once-daily
      (qAM) MAS extended release (MAS XR) in a randomized, crossover study; and 2) to
      examine the associations between adherence and efficacy for MAS IR and MAS XR.
      METHODS: Sixty-two adults with ADHD were enrolled and 49 completed the study. The
      treatment condition order (TID-qAM or qAM-TID) was counterbalanced across
      participants, with an intervening washout period of >= 7 days. Adherence was
      assessed via 3 measures: 1) self-report, 2) pill count, and 3) the Medication
      Event Monitoring System (MEMS((r))). The primary efficacy measure was the ADHD
      Rating Scale (ADHD-RS); secondary measures included the Time-Sensitive ADHD
      Symptom Scale (TASS) and Clinical Global Impressions-Severity of Illness (CGI-S)
      scale. RESULTS: Adherence to treatment as measured by self-report and pill count
      was not significantly different between MAS XR and MAS IR. Adherence was
      significantly better for MAS XR than MAS IR for all of the MEMS((r)) measures.
      The mean change in ADHD-RS, TASS, and CGI-S scores at endpoint was significantly
      improved for both MAS IR and MAS XR and did not differ significantly between
      groups. There was not a significant adherence by efficacy interaction.
      CONCLUSION: Adults with ADHD adhered equally well with MAS IR as with MAS XR when
      assessed by pill count and self-report, but not by the MEMS((r)) measures. Both
      treatments significantly reduced ADHD symptoms, and efficacy was not
      significantly different between groups. Adherence was not associated with
      treatment outcome.

PMID- 21904089
TI  - Single-dose pharmacokinetics of NWP06, an extended-release methylphenidate
      suspension, in children and adolescents with ADHD.
AB  - BACKGROUND: Extended-release formulations of stimulants provide once-daily
      treatment options for patients with attention-deficit/hyperactivity disorder
      (ADHD). Such preparations are more convenient and may improve compliance, and
      thus, improve outcomes. Currently, there is no extended-release liquid oral
      preparation of any stimulant. As such, there is a medical need for a liquid
      extended-release preparation of methylphenidate for the management of ADHD in
      children who are unable or unwilling to swallow solid formulations. OBJECTIVE: To
      evaluate the single-dose pharmacokinetics of an extended-release oral liquid
      formulation of methylphenidate (NWP06) in pediatric subjects with ADHD. METHODS:
      Subjects with ADHD received a single oral dose of NWP06 20 or 60 mg. Serial blood
      samples were obtained before and after drug administration for determination of
      plasma methylphenidate concentrations and standard pharmacokinetic parameters.
      Dose- and weight-corrected pharmacokinetic parameters were presented by age group
      (9-12 years and 13-15 years). RESULTS: A total of 14 youths (7 children aged 9-12
      years and 7 adolescents aged 13-15 years) were enrolled and completed the study.
      Body mass index ranged from 12.08 to 34.08 kg/m(2). Mean values of dose and body
      weight-adjusted maximum plasma concentration (Cmax) (23.8, 22.3, 22.1, 25.7
      [ng/mL]/mg) and area under the concentration-time curve (AUC) (208, 199, 239, 210
      [hr.ng/mL]/[mg/kg]) were similar among all age/dose groups, suggesting dose
      proportionality and a similar rate and extent of absorption in children and
      adolescents. Values for Cmax were observed between 2 and 4 hours after the dose.
      The elimination half-life and body weight-adjusted clearance also appeared to be
      independent of dose and age. NWP06 was well tolerated with no serious adverse
      events and no adverse event-related treatment discontinuations. CONCLUSION: There
      were no age-related pharmacokinetic differences after oral administration of
      NWP06 to children or adolescents in this small sample. Over the dose range of
      methylphenidate used in this study (0.45-3.3 mg/kg), the pharmacokinetics of
      NWP06 were linear and dose proportional.

PMID- 21904090
TI  - PDI-4A: an augmented provisional screening instrument assessing 5 additional
      common anxiety-related diagnoses in adult primary care patients.
AB  - Patients with nonpsychotic mental health and emotional problems are commonly seen
      by primary care physicians. The objective of this study was to expand the
      Provisional Diagnostic Instrument-4 (PDI-4) to include a short self-report screen
      for 5 common anxiety-related diagnoses: panic attack (PA), social phobia (SP),
      obsessive-compulsive disorder (OCD), hypochondriasis, and post-traumatic stress
      disorder (PTSD). Primary care patients (N = 343) were originally evaluated with a
      self-report screen comprised of 85 Diagnostic and Statistical Manual of Mental
      Disorders, Fourth Edition symptom-based candidate questions, then interviewed by
      a trained rater for Structured Clinical Interview Research Version (SCID)/Adult
      ADHD Clinician Diagnostic Scale version 1.2 (ACDS) assessment and diagnosis.
      Responses to screening questions were used to calculate sensitivity and
      specificity for an SCID diagnosis, and to select the optimal cutoffs in symptom
      frequency for 1 or 2 questions for each additional anxiety-related diagnosis. The
      PDI-4 Anxiety (PDI-4A) contains 6 items for provisional differential diagnosis of
      PA, SP, OCD, hypochondriasis, and PTSD in addition to items for the PDI-4.
      Sensitivities/specificities were: PA, 88%/68%; SP, 57%/70%; OCD, 88%/61%;
      hypochondriasis, 67%/85%; and PTSD, 71%/72%. Screening for multiple common
      anxiety diagnoses may be desirable, although limitations may include reduced
      sensitivity and specificity for selected diagnoses. The PDI-4A may additionally
      help primary care physicians identify patients with PA, SP, OCD, hypochondriasis,
      and PTSD.

PMID- 21904091
TI  - Understanding and diagnosing shift work disorder.
AB  - A significant proportion of the workforce in industrialized countries (16%) are
      employed as shift workers. These workers may be susceptible to shift work
      disorder (SWD), a circadian rhythm sleep disorder, particularly those who work at
      night or on early-morning shifts. Shift work disorder remains an underdiagnosed
      and undertreated problem among this population. Patients with SWD have difficulty
      initiating sleep and waking up. Often, these patients have excessive sleepiness
      during their work shift. Shift work disorder has been associated with decreased
      productivity, impaired safety, diminished quality of life, and adverse effects on
      health. Several tools have been validated to assess excessive daytime sleepiness
      and are often used to assess excessive nighttime sleepiness, such as that
      experienced in patients with SWD, including the Epworth Sleepiness Scale and the
      Multiple Sleep Latency Test. The criteria for diagnosing SWD as established by
      the American Academy of Sleep Medicine (AASM) and published in the International
      Classification of Sleep Disorders-Second Edition (ICSD-2) were most recently
      updated in 2005 and thus do not contain newer agents approved for use in patients
      with SWD. The symptoms of SWD can be treated using behavioral, prescription, and
      nonprescription therapies. Current treatment guidelines suggest nonpharmacologic
      interventions, such as exercise and exposure to light. In addition, medications
      that contain melatonin or caffeine may have clinical benefits in some patients
      with SWD. However, modafinil and armodafinil are approved by the US Food and Drug
      Administration to improve wakefulness in patients with excessive sleepiness
      associated with SWD, and recent data suggest a clinical benefit. The use of these
      therapies can significantly improve sleep, performance, and quality of life for
      patients with SWD.

PMID- 21904092
TI  - Is shift work making your patient sick? Emerging theories and therapies for
      treating shift work disorder.
AB  - "Shift work" is a term that applies to a wide array of nontraditional work
      schedules. Shift work disorder (SWD) is a circadian rhythm sleep disorder
      experienced by a subset of shift workers that is characterized by excessive
      sleepiness during work and/or insomnia during scheduled sleep times. It is
      estimated to affect up to 2 million Americans, and is associated with increased
      morbidity and mortality from metabolic risk factors, cardiovascular and
      gastrointestinal diseases, depression, accidents, and some kinds of cancers.
      Patient history is all that is needed to make a diagnosis with the International
      Classification of Sleep Disorders-Second Edition criteria as described herein.
      Circadian rhythm disorders, in which an underlying misalignment of circadian
      rhythm with the sleep-wake cycle occurs, may be treated by behavioral and
      pharmacologic approaches, including the use of hypnotics to improve the duration
      of sleep. However, evidence is limited with these approaches in patients
      diagnosed with SWD. Other treatment options may include pharmacologic
      interventions such as modafinil and armodafinil, which have shown efficacy in
      this population. Combined therapy can reduce insomnia and excessive sleepiness,
      and improve attention and alertness during work shifts and the subsequent commute
      home.

PMID- 21904093
TI  - Exploring the correlates of intermediate CAG repeats in Huntington disease.
AB  - OBJECTIVE: To explore the clinical phenotype in individuals with huntingtin gene
      CAG repeat lengths between 27 and 35, a range that is termed "intermediate" and
      below one traditionally considered diagnostic of Huntington disease (HD).
      BACKGROUND: The Prospective Huntington Disease At-Risk Observational Study
      (PHAROS) found that patients with intermediate CAG lengths overlapped with those
      diagnosed as HD (>= 37 CAG repeats) on the Unified Huntington's Disease Rating
      Scale (UHDRS) behavioral measures. Furthermore, several patients with
      intermediate CAG repeats demonstrating clinical (and pathological) evidence of HD
      have been reported. METHODS: We reviewed all cases with intermediate CAG repeats
      who have presented to our clinic, as well as those reported in the literature.
      RESULTS: We describe 4 patients with intermediate repeats evaluated at our center
      whose clinical features were highly suggestive of HD. Investigations for HD
      phenocopies were negative. Anticipation was demonstrated in 1 case with
      supportive neuropathological evidence of HD. Additionally, we describe the
      clinical features of 5 other patients reported in the literature. CONCLUSION:
      Individuals with huntingtin gene CAG repeats in the intermediate (27-35) range
      should be considered at risk for the development of HD, particularly if they have
      a family history of HD, whether they exhibit clinical features of the disease.

PMID- 21904094
TI  - Age of depressed patient does not affect clinical outcome in collaborative care
      management.
AB  - Clinical response and remission for the treatment of depression has been shown to
      be improved utilizing collaborative care management (CCM). Prior studies have
      indicated that the presence of mental health comorbidities noted by self-rated
      screening tools at the intake for CCM are associated with worsening outcomes; few
      have examined directly the impact of age on clinical response and remission. The
      hypothesis was that when controlling for other mental health and demographic
      variables, the age of the patient at implementation of CCM does not significantly
      impact clinical outcome, and that CCM shows consistent efficacy across the adult
      age spectrum. We performed a retrospective chart analysis of a cohort of 574
      patients with a clinical diagnosis of major depression (not dysthymia) treated in
      CCM who had 6 months of follow-up data. Using the age group as a categorical
      variable in logistic regression models demonstrated that while maintaining
      control of all other variables, age grouping remained a nonsignificant predictor
      of clinical response (P >= 0.1842) and remission (P >= 0.1919) after 6 months of
      treatment. In both models, a lower Generalized Anxiety Disorder-7 score and a
      negative Mood Disorder Questionnaire score were predictive of clinical response
      and remission. However, the initial Patient Health Questionnaire-9 score was a
      statistically significant predictor only for clinical remission (P = 0.0094), not
      for response (P = 0.0645), at 6 months. In a subset (n = 295) of the study
      cohort, clinical remission at 12 months was also not associated with age grouping
      (P >= 0.3355). The variables that were predictive of remission at 12 months were
      the presence of clinical remission at 6 months (odds ratio [OR], 7.4820;
      confidence interval [CI], 3.9301-14.0389; P < 0.0001), clinical response (with
      persistent symptoms) (OR, 2.7722; CI, 1.1950-6.4313; P = 0.0176), and a lower
      initial Patient Health Questionnaire-9 score (OR, 0.9121; CI, 0.8475-0.9816; P =
      0.0140). Our study suggests that using CCM for depression treatment may transcend
      age-related differences in depression and result in positive outcomes regardless
      of age.

PMID- 21904095
TI  - Bipolar disorder is common in depressed primary care patients.
AB  - OBJECTIVE: To examine the prevalence and treatment of typical and subsyndromal
      bipolar disorder (BD) in depressed primary care patients. METHODS: Patients with
      a diagnosis of a mood disorder being treated with antidepressants in 2 academic
      family practice clinics underwent a structured diagnostic interview (Mini
      International Neuropsychiatric Inventory) for manic and hypomanic symptoms.
      RESULTS: Of 58 patients evaluated, 19% met full criteria for bipolar I disorder
      and 8.6% for bipolar II disorder; 31% had subsyndromal BD (ie, persistent elation
      or irritability accompanied by additional symptoms of hypomania but not enough
      symptoms to meet full criteria for bipolar I or II disorder). Only 5 patients
      with BD were receiving mood stabilizers, which had not been instituted in any
      patient by the primary care physician. CONCLUSIONS: The high prevalence of
      patients meeting full criteria for BD and the low rate of identification of BD in
      primary care patients are consistent with estimates using self-administered
      questionnaires, but the interview revealed a substantial additional population
      that could be considered to have subsyndromal BD. Because subsyndromal forms of
      BD are associated with significant impairment and comorbidity as well as
      progression to frank BD, recognition of both full and subthreshold BD in primary
      care practice should be improved.

PMID- 21904096
TI  - Review of current guidelines on the care of postherpetic neuralgia.
AB  - An unfortunate minority of patients with acute herpes zoster (AHZ) experience
      pain beyond the typical 4-week duration, and roughly 10% develop the distressing
      complication of postherpetic neuralgia (PHN), often defined as pain persisting
      for > 4 months after the onset of the rash. Elderly patients are at increased
      risk of PHN. The pathophysiology of PHN is complex, likely involving both
      peripheral and central processes. This complexity may create opportunities for
      pharmacologic interventions with multiple differing mechanisms of action.
      Consequently, complementary combinations of pharmacologic agents are frequently
      more effective than any monotherapy. Current US and international guidelines on
      the care of patients with PHN are reviewed and interpreted here to facilitate
      their effective incorporation into the practice of primary care physicians,
      acknowledging the contrasts that often exist between the clinical trial
      populations analyzed to craft so-called evidence-based medicine and the
      individual patients seen in daily practice, many of whom may not have been
      candidates for those clinical trials. First-line treatments for PHN include
      tricyclic antidepressants, gabapentin and pregabalin, and the topical lidocaine
      5% patch. Opioids, tramadol, capsaicin cream, and the capsaicin 8% patch are
      recommended as either second- or third-line therapies in different guidelines.
      Therapies that have demonstrated effectiveness for other types of neuropathic
      pain are discussed, such as serotonin-norepinephrine reuptake inhibitors, the
      anticonvulsants carbamazepine and valproic acid, and botulinum toxin. Invasive
      procedures such as sympathetic blockade, intrathecal steroids, and implantable
      spinal cord stimulators have been studied for relief of PHN, mainly in patients
      refractory to noninvasive pharmacologic interventions. The main guidelines
      considered here are those issued by the American Academy of Neurology for the
      treatment of postherpetic neuralgia (2004) and general guidelines for the
      treatment of neuropathic pain issued by the Special Interest Group on Neuropathic
      Pain of the International Association for the Study of Pain (2007) and the
      European Federation of Neurological Societies (2010).

PMID- 21904097
TI  - Management of chronic noncancer pain in depressed patients.
AB  - Many patients with chronic noncancer pain present with comorbid depression, which
      can greatly complicate the treatment of pain. Chronic pain and depression each
      increase the risk of licit and illicit substance abuse, including the abuse of
      opioids, and of suicide. Patients attempting suicide may overdose on opioids,
      which are commonly perceived as potentially harmful, or acetaminophen, an agent
      that is believed to be safe but is actually the leading cause of liver failure in
      the United States. Opioids, acetaminophen, and nonsteroidal anti-inflammatory
      drugs (NSAIDs) have the potential to interact with antidepressants, and their
      adverse effects may be exacerbated by alcohol use, which is also common in
      patients with depression. Topical NSAIDs, capsaicin, and lidocaine provide
      effective analgesia for several pain conditions. These agents limit systemic drug
      exposure, reducing the risk of systemic adverse events without risk of accidental
      or deliberate overdose. However, use of topical agents is generally limited to
      localized pain syndromes and therefore does not substantially eliminate the need
      for systemic analgesics in those patients with diffuse persistent pain, central
      sensitization, and opioid-responsive pain. This review will discuss the
      challenges associated with treating chronic pain in depressed patients and will
      provide recommendations for optimizing treatment.

PMID- 21904098
TI  - Opioid titration and conversion in patients receiving morphine sulfate and
      naltrexone hydrochloride extended release capsules.
AB  - OBJECTIVE: To determine the number of steps and identify characteristics
      associated with attaining a stable dose of morphine sulfate and sequestered
      naltrexone extended release capsules (MS-sNT). PATIENTS AND METHODS: Data from an
      open-label, long-term multicenter study designed to assess the safety of MS-sNT
      for managing chronic (>= 3 m), moderate-to-severe pain were analyzed post hoc.
      Initial MS-sNT dose was 20 mg twice daily (BID) for opioid-naive patients and 50%
      to 75% of current daily opioid dose for opioid-experienced patients. Dose
      adjustments upward/downward were allowed throughout the study with >= 3 days
      between increases; opioid-experienced patients could increase >= 24 hours after
      initial drug dispensing. Nonopioid analgesics were permitted as rescue
      medication. Stable dose was defined post hoc as one maintained for 2 consecutive
      study visits. RESULTS: Overall, 69% of patients (n = 319/465) achieved a stable
      dose; 85% (n = 272) achieved a stable dose in <= 2 titration dose adjustments or
      "steps," and 96% (n = 305) achieved a stable dose in <= 4 steps. The mean time to
      stable dose was 28.9 days (standard deviation [SD], 34.1 days); the median was 12
      days. A stable dose was achieved in 70% (118/168) of opioid-naive patients (mean,
      24.2 days [SD, 33.4 days]; median, 8 days) and 68% (201/297) of opioid
      experienced patients (mean, 31.7 days [SD, 34.3 days]; median, 25 days). A stable
      dose was achieved by 79% (19/24) of patients who previously used morphine, 64%
      (27/42) who used oxycodone, 59% (47/79) who used hydrocodone, and 71% (83/117)
      who used multiple opioids. Baseline pain scores were similar between patients who
      did and did not achieve a stable dose. At the time of stable dose achievement,
      average, least, worst, and current pain were all decreased from baseline.
      CONCLUSIONS: The study provides information about anticipated rates of achieving
      stable opioid dose in patients who received MS-sNT for up to 1 year to manage
      chronic, moderate-to-severe pain. Both opioid-naive and opioid-experienced
      patients achieved a stable dose of MS-sNT, generally in <= 2 steps. Opioid
      experience and previous opioid use may influence ability to achieve a stable dose
      and number of steps required. More studies are needed on the anticipated
      experience of opioid titration/conversion to help physicians and patients set
      expectations for initiation of and conversion between opioid therapies.

PMID- 21904099
TI  - Psychological risk factors and cardiovascular disease: is it all in your head?
AB  - Psychological stress has been shown to be associated with cardiovascular disease.
      Over the past few decades, there has been an increasing interest in this
      relationship, leading to a growing pool of clinical and epidemiological data on
      the subject. Psychological stress has multiple etiologies, which include
      behavioral causes, acute events or stressors, and/or chronic stress. Cardiac
      rehabilitation and exercise therapy have been shown to provide protection in
      primary and secondary coronary heart disease prevention, as well as improve
      overall morbidity and mortality. In this article, we review the available data
      regarding the association between psychological stress and cardiovascular
      disease, as well as the impact of cardiac rehabilitation and exercise therapy on
      psychological stress-related cardiovascular events.

PMID- 21904100
TI  - The role of the primary care physician in managing early stages of chronic kidney
      disease.
AB  - Recent increases in obesity, diabetes, and hypertension, along with the aging of
      the US population, are driving a dramatic rise in the prevalence of chronic
      kidney disease (CKD). Despite this increase, the majority of Americans with early
      stage CKD remain unaware of their disease. Primary care physicians are at the
      forefront of efforts for early recognition of CKD and management to control its
      progression. Patients with CKD should be referred to nephrologists no later than
      the point at which their estimated glomerular filtration rate reaches 30 mL/min.
      Nephrology evaluation at this point is essential to facilitate timely preparation
      for care of end-stage renal disease through preemptive transplantation or planned
      transition to dialysis. In addition to stringent control of underlying
      hypertension and/or diabetes, mineral metabolic parameters (serum parathyroid
      hormone, phosphorus, calcium, and bicarbonate) in patients with advancing CKD
      should be managed closely to avoid adverse effects on the cardiovascular and
      skeletal systems.

PMID- 21904101
TI  - Safety and efficacy of home-based subcutaneous immunoglobulin G in elderly
      patients with primary immunodeficiency diseases.
AB  - BACKGROUND: Subcutaneous immunoglobulin (SCIG) is as effective as intravenous
      immunoglobulin (IVIG) in minimizing infections in patients with primary
      immunodeficiency diseases (PIDD) and is associated with fewer systemic adverse
      events (AEs). Self-infusion/home-based infusion of SCIG improves quality of life
      and may lower treatment costs compared with hospital or office-based IVIG
      therapy, but its suitability has not been assessed in elderly patients (>= 65
      years). METHODS: We conducted a retrospective chart review of 47 elderly patients
      with PIDD in a single clinical practice in the United States to evaluate the
      practicality, safety, and efficacy of home-based SCIG infusions in elderly
      patients with PIDD over a 13-month period. Measurements included baseline disease
      characteristics, previous and current immunoglobulin G (IgG) replacement
      regimens, self-administered versus assisted SCIG infusions, SCIG infusion
      parameters, serum IgG levels, infections, and AEs. RESULTS: Forty-seven of 111
      elderly patients (42%) treated with IgG in this practice elected to receive SCIG.
      All 47 patients received SCIG infusions at home; 39 (83.0%) self-infused the
      medication. Most patients (n = 46; 98%) received weekly infusions, requiring a
      mean duration of 65.3 minutes. The mean SCIG dose of 103 mg/kg/week resulted in a
      mean steady-state serum IgG concentration of 1074 mg/dL. Two patients experienced
      serious infections on SCIG: an exacerbation of chronic obstructive pulmonary
      disease/bronchitis, and an abscess. There were no serious systemic AEs. Local
      injection site reactions, including swelling, redness, burning, or itching, were
      considered mild or moderate by the patients and resolved within 24 hours. No
      bruising, bleeding, or skin breakdown occurred, despite concomitant anticoagulant
      or platelet inhibitor treatment in 45% of patients. Two patients discontinued
      home-based SCIG, but did not continue any IgG treatment. No patient switched from
      SCIG to another route of IgG treatment. CONCLUSIONS: Home-based SCIG is safe and
      effective in elderly patients with PIDD, most of whom can self-infuse. Infection
      rates were low, and no AEs or difficulties in administering SCIG occurred that
      resulted in treatment discontinuation.

PMID- 21904102
TI  - Key concepts of clinical trials: a narrative review.
AB  - The recent focus of federal funding on comparative effectiveness research
      underscores the importance of clinical trials in the practice of evidence-based
      medicine and health care reform. The impact of clinical trials not only extends
      to the individual patient by establishing a broader selection of effective
      therapies, but also to society as a whole by enhancing the value of health care
      provided. However, clinical trials also have the potential to pose unknown risks
      to their participants, and biased knowledge extracted from flawed clinical trials
      may lead to the inadvertent harm of patients. Although conducting a well-designed
      clinical trial may appear straightforward, it is founded on rigorous methodology
      and oversight governed by key ethical principles. In this review, we provide an
      overview of the ethical foundations of trial design, trial oversight, and the
      process of obtaining approval of a therapeutic, from its pre-clinical phase to
      post-marketing surveillance. This narrative review is based on a course in
      clinical trials developed by one of the authors (DJM), and is supplemented by a
      PubMed search predating January 2011 using the keywords "randomized controlled
      trial," "patient/clinical research," "ethics," "phase IV," "data and safety
      monitoring board," and "surrogate endpoint." With an understanding of the key
      principles in designing and implementing clinical trials, health care providers
      can partner with the pharmaceutical industry and regulatory bodies to effectively
      compare medical therapies and thereby meet one of the essential goals of health
      care reform.

PMID- 21904104
TI  - Primary care physician attitudes and practice patterns in the management of obese
      adults: results from a national survey.
AB  - PURPOSE: Obesity remains a serious public health problem. The purpose of this
      study was to identify the current attitudes and practices of primary care
      physicians (PCPs) with respect to obesity. METHODS: A survey was systematically
      developed and administered electronically to PCPs, who received a small
      honorarium for their time. Results were analyzed to identify specific attitudes
      and practices and their associations with each other and with demographic and
      other variables. RESULTS: Physicians expressed little confidence in their ability
      to manage obesity. In general, however, they believed that obesity could be
      successfully managed. Lifestyle changes were perceived to be the most effective
      available method for patients to lose weight, and respondents were more likely to
      recommend this approach over pharmacotherapy or bariatric surgery. Respondents
      perceive the greatest barrier to managing obese patients to be a lack of patient
      motivation. Physicians were significantly more likely to initiate discussions
      with obese patients about their weight if they believed they had positive
      attitudes about and knowledge of weight management, and adequate resources to
      manage the problem. CONCLUSIONS: Physicians report a lack of confidence in
      managing obesity. Lack of patient motivation is perceived to be the greatest
      barrier. Physicians with greater knowledge, more positive attitudes toward
      obesity management, and access to more resources are more likely to provide
      weight management in primary care settings.

PMID- 21904103
TI  - Effect of a behavioral/nutritional intervention program on weight loss in obese
      adults: a randomized controlled trial.
AB  - BACKGROUND: Health professionals are in need of more information about the weight
      loss outcomes of using commercial weight-loss programs. OBJECTIVE: A commercial
      behavioral intervention program using meal replacements, fruits, and vegetables
      (MR-FV) was compared with usual-care weight-loss counseling. DESIGN: Obese
      volunteers were randomly allocated to usual-care weight-loss counseling or
      participation in an MR-FV standardized behavioral education program. The MR-FV
      group attended weekly weight-loss classes for 16 weeks and weekly maintenance
      classes for 8 weeks. PARTICIPANTS/SETTING: Obese women or men aged 20 to 65 years
      were recruited from the community through a commercial program provided at a
      university medical center. INTERVENTION: The control group (C group) received
      weight-management counseling from an experienced dietitian, while the
      intervention group (MR-FV group) participated in scheduled behavioral weight-loss
      classes. The MR-FV group participants were encouraged to consume 3 shakes, 2
      entrees, and 5 servings of fruits or vegetables daily, and achieve physical
      activity goals (expend >= 8.4 mJ/week); they kept records and placed midweek
      phone calls. The C group was counseled at baseline, 8 weeks, and 16 weeks.
      OUTCOME MEASURES: Both groups were seen at baseline, and 8, 16, and 24 weeks for
      assessment of weight, risk factors, and side effects. STATISTICAL ANALYSIS: The
      primary data analysis was intention to treat. RESULTS: Thirteen of 16 subjects
      (81.3%) in the C group and 18 of 22 subjects (81.8%) in the MR-FV group completed
      the 24-week study. Mean weight losses for the C group were: 1.3% (standard error
      [SE], 0.9) at 8 weeks; 0.7% (SE, 1.1) at 16 weeks; and 0.7% (SE, 1.1) or 0.7 kg
      at 24 weeks. Mean weight losses for the MR-FV group were: 8.5% (SE, 0.6) at 8
      weeks, 12.5% (SE, 0.9) at 16 weeks, and 13.9% (SE, 1.1) or 13.7 kg at 24 weeks.
      CONCLUSIONS: A behavioral intervention with a low-energy diet including 5 meal
      replacements and 5 servings of fruits or vegetables enabled obese individuals to
      lose 13 kg more than control subjects over a 24-week period.

PMID- 21904105
TI  - Treatment of rheumatoid arthritis with roxithromycin: a randomized trial.
AB  - BACKGROUND: High levels of antibodies to oral anaerobic bacteria have been found
      in the serum and synovial fluid of patients with rheumatoid arthritis (RA).
      Macrolide antibiotics are active against oral anaerobic bacteria. The aim of this
      trial was to evaluate the efficacy of roxithromycin in patients with RA who had
      not responded to disease-modifying antirheumatic drugs. METHODS: This was a 6
      month, randomized, double-blind, placebo-controlled trial. We treated 100
      patients with active RA with either once-daily oral roxithromycin 300 mg or daily
      oral placebo for 6 months. The primary efficacy variable was the percentage of
      patients who had a 20% improvement according to the American College of
      Rheumatology (ACR) criteria (an ACR20 response) at 6 months. Secondary outcome
      measures were 50% improvement and 70% improvement according to ACR criteria (an
      ACR50 response and an ACR70 response, respectively). RESULTS: A significantly
      greater percentage of patients treated with roxithromycin 300 mg met the ACR 20%
      improvement criteria (ie, achieved an ACR20 response) at 6 months compared with
      patients who received placebo (60% vs 34%; P = 0.009). Greater percentages of
      patients treated with roxithromycin 300 mg also achieved ACR50 responses (38% vs
      12%; P = 0.003) and ACR70 responses (18% vs 2%; P = 0.008) compared with patients
      who received placebo. Roxithromycin was well tolerated, with an overall safety
      profile similar to that of placebo. CONCLUSION: In patients with active RA,
      treatment with roxithromycin significantly improved the signs and symptoms of RA.

PMID- 21904106
TI  - Clinical implications of exenatide as a twice-daily or once-weekly therapy for
      type 2 diabetes.
AB  - Exenatide (exendin-4) is a 39-amino acid peptide belonging to the glucagon-like
      peptide-1 (GLP-1) receptor agonist class that has been demonstrated to improve
      glycemic control in patients with type 2 diabetes mellitus. Exenatide can be
      injected twice daily (ExBID) before meals or once weekly (ExQW) when encompassed
      within dissolvable poly-(D,L-lactide-co-glycolide) microspheres. The primary
      difference between these formulations is the plasma concentration of exenatide
      over time, with the long-acting form providing continuous delivery. Clinical
      trials have examined the similarities and differences in the efficacy and
      safety/tolerability outcomes of these formulations. In 2 clinical studies
      spanning 24 and 30 weeks, significant (P < 0.05) reductions from baseline were
      observed in fasting plasma glucose (ExBID, -12 and -25 mg/dL; ExQW, -35 and -41
      mg/dL), postprandial glucose (ExBID, -124 mg/dL; ExQW, -95 mg/dL), and glycated
      hemoglobin (HbA1c) (ExBID, -0.9% and -1.5%; ExQW, -1.6% and -1.9%). Reductions in
      body weight from baseline were significant and similar with both treatments
      (ExBID, -1.4 and -3.6 kg; ExQW, -2.3 and -3.7 kg). Reductions in systolic blood
      pressure from baseline were observed with both formulations, particularly in
      patients who were hypertensive at baseline. Beneficial improvements in lipid
      profiles were small and fluctuated in significance. Patients reported greater
      treatment satisfaction with ExQW compared with ExBID dosing. Gastrointestinal
      adverse events were commonly observed with both formulations but were less
      frequent with ExQW. These events were of mild-to-moderate intensity and rarely
      led to discontinuation. Real-world data for ExBID demonstrated decreases in
      HbA1c, fasting plasma glucose, and body weight that were consistent with clinical
      trial results. Cases of pancreatitis or renal impairment have been reported in
      patients treated with ExBID, although no causal relationship with treatment has
      been shown. This review describes the similarities and differences between
      exenatide delivered as a twice-daily or as a once-weekly injection to provide a
      better understanding of the clinical effects and potential clinical uses of each.

PMID- 21904107
TI  - Next-generation GLP-1 therapy: an introduction to liraglutide.
AB  - Liraglutide, a once-daily human glucagon-like peptide-1 (GLP-1) analog, was
      approved by the US Food and Drug Administration in 2010 for the treatment of type
      2 diabetes mellitus (T2DM). Glucagon-like peptide-1 enhances insulin secretion
      and inhibits glucagon in a glucose-dependent manner. The efficacy and safety of
      liraglutide were evaluated in 6 phase 3 trials in > 4000 patients in the
      Liraglutide Effect and Action in Diabetes (LEAD) program, in another trial in
      comparison with sitagliptin, and in another trial where basal insulin was added
      to liraglutide + metformin. At liraglutide doses of 1.2 mg or 1.8 mg once daily,
      significant mean reductions in glycated hemoglobin (HbA1c) (1%-1.6%) and fasting
      plasma glucose (15-43 mg/dL), as well as sustained weight loss (2-3 kg) and a low
      rate of hypoglycemia occurred. Mild and transient nausea, reported in 6% to 41%
      of patients, was the most frequent adverse event reported. Incretin-based
      therapies such as liraglutide provide an important expansion of options for the
      treatment of T2DM.

PMID- 21904108
TI  - Letter to the editor: The importance of differentiating between topical NSAIDs.

PMID- 21904110
TI  - Induction of steroid sulfatase expression by tumor necrosis factor-alpha through
      phosphatidylinositol 3-kinase/Akt signaling pathway in PC-3 human prostate cancer
      cells.
AB  - Steroid sulfatase (STS) is responsible for the hydrolysis of aryl and alkyl
      steroid sulfates and has a pivotal role in regulating the formation of
      biologically active estrogens. STS may be considered a new promising drug target
      for treating estrogen-mediated carcinogenesis. However, the molecular mechanism
      of STS expression is not well-known. To investigate whether tumor necrosis factor
      (TNF)-alpha is able to regulate gene transcription of STS, we studied the effect
      of TNF-alpha on STS expression in PC-3 human prostate cancer cells. RT-PCR and
      Western blot analysis showed that TNF-alpha significantly induced the expression
      of STS mRNA and protein in a concentration- and time-dependent manner. Treatment
      with TNF-alpha resulted in a strong increase in the phosphorylation of Akt on Ser
      473 and when cells were treated with phosphatidylinositol (PI) 3-kinase
      inhibitors such as LY294002 or wortmannin, or Akt inhibitor (Akt inhibitor IV),
      induction of STS mRNA expression by TNF-alpha was significantly prevented.
      Moreover, activation of Akt1 by expressing the constitutively active form of Akt1
      increased STS expression whereas dominant-negative Akt suppressed TNF-alpha
      mediated STS induction. We also found that TNF-alpha is able to increase STS mRNA
      expression in other human cancer cells such as LNCaP, MDA-MB-231, and MCF-7 as
      well as PC-3 cells. Taken together, our results strongly suggest that PI 3
      kinase/Akt activation mediates induction of human STS gene expression by TNF
      alpha in human cancer cells.

PMID- 21904111
TI  - Interaction of TCP4-mediated growth module with phytohormones.
AB  - TCP4 and related members of class II TCP genes regulate leaf morphogenesis. We
      earlier demonstrated that level of TCP4 activity determines leaf size and aspects
      of plant maturity. The mechanism of TCP function and their target genes remain
      unidentified, limiting our understanding of TCP-mediated growth control. As leaf
      growth is influenced simultaneously by multiple phytohormones, we have studied if
      TCP4 interacts with any of the hormone-response pathways. Our analyses indicate a
      role for auxin, gibberellic acid and abscisic acid in TCP4-mediated control of
      leaf growth.

PMID- 21904112
TI  - A non-destructive screenable marker, OsFAST, for identifying transgenic rice
      seeds.
AB  - The production of transgenic plants has contributed greatly to plant research.
      Previously, an improved method for screening transgenic Arabidopsis thaliana
      seeds using the FAST (Fluorescence-Accumulating-Seed Technology) method and FAST
      marker was reported. Arabidopsis seeds containing the FAST marker may be visually
      screened using a fluorescence stereomicroscope or blue LED handy-type instrument.
      Although the FAST method was originally designed for Arabidopsis screens, this
      study endeavors to adapt this method for the screening of other plants. Here, an
      optimized technology, designated the OsFAST method, is presented as a useful tool
      for screening transgenic rice seeds. The OsFAST method is based on the expression
      of the OsFAST-G marker under the control of a seed-embryo-specific promoter,
      similar to the Arabidopsis FAST-G marker. The OsFAST method provides a simple and
      non-destructive method for identifying transgenic rice seeds. It is proposed that
      the FAST method is adaptable to various plant species and will enable a deeper
      analysis of the floral-dip method. 

PMID- 21904113
TI  - Evolutionary origin of rhizobium Nod factor signaling.
AB  - For over two decades now, it is known that the nodule symbiosis between legume
      plants and nitrogen fixing rhizobium bacteria is set in motion by the bacterial
      signal molecule named nodulation (Nod) factor. Upon Nod factor perception a
      signaling cascade is activated that is also essential for endomycorrhizal
      symbiosis (Fig. 1). This suggests that rhizobium co-opted the evolutionary far
      more ancient mycorrhizal signaling pathway in order to establish an endosymbiotic
      interaction with legumes. As arbuscular mycorrhizal fungi of the Glomeromycota
      phylum can establish a symbiosis with the fast majority of land plants, it is
      most probable that this signaling cascade is wide spread in plant kingdom.
      However, Nod factor perception generally is considered to be unique to legumes.
      Two recent breakthroughs on the evolutionary origin of Rhizobium Nod factor
      signaling demonstrate that this is not the case. The purification of Nod factor
      like molecules excreted by the mycorrhizal fungus Glomus intraradices and the
      role of the LysM-type Nod factor receptor PaNFP in the non-legume Parasponia
      andersonii provide novel understanding on the evolution of rhizobial Nod factor
      signaling.

PMID- 21904114
TI  - Mannan synthase activity in the CSLD family.
AB  - Cellulose Synthase Like (CSL) proteins are a group of plant glycosyltransferases
      that are predicted to synthesize beta-1,4-linked polysaccharide backbones. CSLC,
      CSLF and CSLH families have been confirmed to synthesize xyloglucan and mixed
      linkage beta-glucan, while CSLA family proteins have been shown to synthesize
      mannans. The polysaccharide products of the five remaining CSL families have not
      been determined. Five CSLD genes have been identified in Arabidopsis thaliana and
      a role in cell wall biosynthesis has been demonstrated by reverse genetics. We
      have extended past research by producing a series of double and triple
      Arabidopsis mutants and gathered evidence that CSLD2, CSLD3 and CSLD5 are
      involved in mannan synthesis and that their products are necessary for the
      transition between early developmental stages in Arabidopsis. Moreover, our data
      revealed a complex interaction between the three glycosyltransferases and brought
      new evidence regarding the formation of non-cellulosic polysaccharides through
      multimeric complexes.

PMID- 21904116
TI  - Resveratrol fails to improve marginal mass engraftment of transplanted islets of
      Langerhans in mice.
AB  - One limitation of current islet transplantation protocols is the loss of up to
      70% of the transplanted islet mass. Inflammatory events play a major role in
      islet loss including the cytokines TNFalpha and IL-1. Resveratrol, a compound
      with anti-inflammatory and anti-oxidant properties, has the potential to mitigate
      islet loss. Using a syngeneic marginal  after mouse islet transplantation model
      we tested the ability of resveratrol to enhance islet engraftment. We failed to
      show a difference in diabetes reversal between mice treated with vehicle and
      those treated with either 10 mg/kg (47.1% for resveratrol vs. 35.3% for control)
      or 50 mg/kg (20% for resveratrol vs. 22.2% for control) of resveratrol daily for
      three weeks. In addition, at one month there was no difference in glucose
      tolerance or graft survival (10 mg/kg: 552.6 ng/ml resveratrol group vs. 576.6
      ng/ml control group; 50 mg/kg: 463 ng/ml resveratrol group vs. 444.1 ng/ml
      control group). In summary, over a wide range of doses, resveratrol did not exert
      a benefit on mouse islet engraftment. Further studies should be conducted with
      human islets before deeming resveratrol ineffective in islet engraftment and
      survival.

PMID- 21904115
TI  - AtMKK6 and AtMPK13 are required for lateral root formation in Arabidopsis.
AB  - The mitogen-activated protein (MAP) kinase cascades are important signaling
      components that mediate various biological pathwaysin all eukaryotic cells. In
      our recent publication,1 we identified AtMPK4 as one of the downstream targets of
      AtMKK6 that is required for executing male-specific meiotic cytokinesis. Here we
      provide evidence that another target, AtMPK13, is developmentally co-expressed
      with AtMKK6 in Arabidopsis, and both AtMPK13 and AtMKK6 display high
      Promoter::GUS activity in the primary root tips and at the lateral root
      primordia. Partial suppression of either AtMKK6 or AtMPK13 expression
      significantly reduces the number of lateral roots in the transgenic lines,
      suggesting that the AtMKK6-AtMPK13 module positively regulates lateral root
      formation.

PMID- 21904117
TI  - Casparian strip development and its potential function in salt tolerance.
AB  - The root system is particularly affected by unfavourable conditions because it is
      in direct contact with the soil environment. Casparian strips, a specialised
      structure deposited in anticlinal walls, are characterised by the impregnation of
      the primary wall pores with lignin and suberin. The Casparian strips in the endo-
      and exodermis of vascular plant roots appear to play an important role in
      preventing the non-selective apoplastic bypass of salts into the stele along the
      apoplast under salt stress. However, only a few investigations have examined the
      deposition and function of these apoplastic barriers in response to salt stress
      in higher plants.

PMID- 21904118
TI  - Hydrogen sulfide effects on stomatal apertures.
AB  - Hydrogen sulfide (H(2)S) has recently been reported to be a signaling molecule in
      plants. It has been well established that is has such roles in animals and it has
      been suggested that it is included into the group of gasotransmitters. We have
      recently shown that hydrogen sulfide causes stomatal opening in the model plant
      Arabidopsis thaliana. H(2)S can be supplied to the plant tissues from donors such
      as sodium hydrosulfide (NaSH) or more recently from slow release H(2)S donor
      molecules such as GYY4137. Both give similar effects, that is, they cause
      stomatal opening. Furthermore both H(2)S donors reduced the accumulation of
      nitric oxide (NO) induced by abscisic acid (ABA) treatment of leaf tissues. Here
      similar work has been repeated in a crop plant, Capsium anuum, and similar data
      has been obtained, suggesting that such effects of hydrogen sulfide on plants is
      not confined to model species.

PMID- 21904120
TI  - The first use of an investigational multicomponent meningococcal serogroup B
      vaccine (4CMenB) in humans.
AB  - BACKGROUND: Neisseria meningitidis serogroup B is a well-recognized cause of
      bacterial meningitis and sepsis for which no broadly protective vaccine exists.
      Whole genome sequencing was used to identify three antigens: factor H binding
      protein (fHbp), Neisserial adhesin A (NadA), and Neisseria heparin binding
      antigen (NHBA) for an investigational vaccine candidate (rMenB). This was the
      first trial of an investigational multicomponent meningococcal serogroup B
      vaccine (4CMenB), containing rMenB and outer membrane vesicles (OMV) from the New
      Zealand epidemic strain in humans. RESULTS: Seventy adults enrolled and received
      study vaccine. All vaccines were generally well tolerated. Immune responses were
      observed to multiple serogroup B strains following all investigational vaccines,
      suggesting the potential for broad coverage against this serogroup.
      Immunogenicity was enhanced by the addition of OMV; the 4CMenB displayed the
      optimal profile for further investigation. METHODS: In a phase I, observer blind,
      randomized trial, healthy adults (18-40 years of age) were randomized 2:2:1 to
      receive 3 doses of 4CMenB, rMenB with OMV from the Norwegian outbreak strain, or
      rMenB alone. Pre- and postvaccination sera were evaluated in a serum bactericidal
      assay using human complement (hSBA) against a panel of 15 serogroup B strains,
      with titers >= 4 considered protective. Solicited injection site and systemic
      reactions were evaluated for 7 days following each vaccination and adverse events
      were reported throughout the study. CONCLUSION: In this trial, 4CMenB displayed a
      favorable profile for further clinical development. 4CMenB demonstrated
      immunogenicity against multiple heterologous serogroup B strains. All vaccines
      were generally well tolerated in this study.

PMID- 21904122
TI  - Bibliography. Atherosclerosis: cell biology and lipoproteins. Current world
      literature.

PMID- 21904123
TI  - Controversies in nutrition: calcium and heart disease is there a problem?

PMID- 21904119
TI  - Interactions between enhancer of rudimentary and Notch and deltex reveal a
      regulatory function of enhancer of rudimentary in the Notch signaling pathway in
      Drosophila melanogaster.
AB  - Enhancer of rudimentary, e(r), encodes a small nuclear protein, ER, that has been
      implicated in the regulation of pyrimidine metabolism, DNA replication, and cell
      proliferation. In Drosophila melanogaster, a new recessive Notch allele, N (nd-p)
      , was isolated as a lethal in combination with an e(r) allele, e(r) (p2) . Both
      mutants are viable as single mutants. N (nd-p) is caused by a P-element insertion
      in the 5' UTR, 378-bp upstream of the start of translation. Together the
      molecular and genetic data argue that N (nd-p) is a hypomorphic allele of N. The
      three viable notchoid alleles, N (nd-p) , N (nd-1) , and N (nd-3) , are lethal in
      combination with e(r) (-) alleles. Our present hypothesis is that e(r) is a
      positive regulator of the Notch signaling pathway and that the lethality of the N
      e(r) double mutants is caused by a reduction in the expression of the pathway.
      This is supported by the rescue of the lethality by a mutation in Hairless, a
      negative regulator of N, and by the synthetic lethality of dx e(r) double
      mutants. Further support for the hypothesis is a reduction in E(spl) expression
      in an e(r) (-) mutant. Immunostaining localizes ER to the nucleus, suggesting a
      nuclear function for ER. A role in the Notch signaling pathway, suggests that
      e(r) may be expressed in the nervous system. This turns out to be the case, as
      immunostaining of ER shows that ER is localized to the developing CNS.

PMID- 21904124
TI  - Genetics and molecular biology: fatty acid metabolism in cancer cell survival;
      carnitine palmitoyltransferase-1 as a critical anticancer target.

PMID- 21904125
TI  - Atherosclerosis: cell biology and lipoproteins.

PMID- 21904126
TI  - Lipid metabolism.

PMID- 21904128
TI  - Anal vector volumetry: a bridge too far.

PMID- 21904132
TI  - Sessile serrated adenoma/polyp of the large intestine: a potentially aggressive
      lesion in need of a new screening strategy.

PMID- 21904133
TI  - Choosing your goals.

PMID- 21904134
TI  - Who performs proctectomy for rectal cancer in the United States?
AB  - BACKGROUND: There is wide variation in surgical care for rectal cancer in the
      United States. OBJECTIVE: This study aimed to assess the differences in
      individual surgeon procedural profiles that might explain variations in the rates
      of restorative vs nonrestorative proctectomy for rectal cancer. DESIGN: This
      study was a retrospective examination of a cohort derived from trackable state
      hospital discharge data from 11 states. PATIENTS: We identified all patients with
      rectal cancer that underwent restorative proctectomy (sphincter-sparing surgery)
      vs nonrestorative proctectomy (colostomy formation) over a 24-month study period
      (January 1, 2003 through December 31, 2004). INTERVENTION: We developed an
      inpatient procedural profile of each treating surgeon's practice across general
      surgery procedure codes and summed the number of restorative vs nonrestorative
      proctectomies for rectal cancer by surgeon. MAIN OUTCOME MEASURES: The primary
      outcome measures were nonrestorative proctectomy, mortality, and length of stay.
      RESULTS: A total of 7519 proctectomies were performed for rectal cancer by 2588
      surgeons. During the 24-month study period, 1003 (38.8%) surgeons performed only
      nonrestorative procedures for rectal cancer. On multivariate analysis, the
      likelihood that a surgeon performed only nonrestorative procedures was increased
      if that surgeon performed more integumentary procedures and decreased if the
      surgeon performed at least one ileoanal pouch procedure or more anorectal
      procedures. Patients who underwent proctectomy by surgeons who performed only
      nonrestorative procedures had significantly higher mortality (2.5 +/- 0.7%) and
      longer length of stay (11.3 +/- 8.8 days) in comparison with those patients
      treated by surgeons who performed both restorative and nonrestorative procedures
      (1.3 +/- 0.3% mortality and 9.2 +/- 6.9 days, P < .001 for both analyses). The
      volume of proctectomy performed significantly affected all analyses. LIMITATIONS:
      : The retrospective design introduces potential selection bias. CONCLUSIONS: Over
      a 24-month period, 38.8% of surgeons performed only nonrestorative procedures for
      rectal cancer. These surgeons did not regularly perform anorectal or ileoanal
      pouch procedures, suggesting that they may not have a focus on colorectal disease
      in their practice; they had significantly higher mortality and length of stay for
      their patients who underwent proctectomy for rectal cancer.

PMID- 21904135
TI  - Individuals with sessile serrated polyps express an aggressive colorectal
      phenotype.
AB  - BACKGROUND: Sessile serrated polyps are precursors of colorectal cancer arising
      from molecular pathways distinct from conventional adenomas. The association
      between sessile serrated polyps and conventional adenomas is not well known.
      OBJECTIVE: We hypothesize that individuals who have coexistent sessile serrated
      polyps and conventional adenomas express a more severe phenotype than those
      harboring lesions from only one pathway. We compare colorectal phenotypes among
      individuals with sessile serrated polyps, those with conventional adenomas, and
      those expressing both. DESIGN: This investigation is a retrospective cross
      sectional study of 3 cohorts. SETTINGS: This study was conducted in multiple
      centers within 1 health care system. PATIENTS: Individuals with sessile serrated
      polyps and/or conventional adenomas on first lifetime colonoscopy were included
      in the study. MAIN OUTCOME MEASURES: The demographics and polyp characteristics
      were compared among 3 cohorts to determine the differences in phenotypic
      expression. RESULTS: Two hundred sixty individuals with sessile serrated polyps
      and 173 with only conventional adenomas were included. The disease phenotype was
      most severe in individuals with coexistent sessile serrated polyps and adenomas.
      The sessile serrated polyps in this cohort were larger (P = .01) than in the
      serrated-only cohort. The conventional adenomas in this cohort were more numerous
      (P = .035) and more advanced (P = .046) than in the adenoma-only cohort.
      Synchronous colorectal cancers were found exclusively in the cohorts with sessile
      serrated polyps, although this did not reach statistical significance (P = .06).
      LIMITATIONS: Cross-sectional design precluded the ability to assess for
      metachronous lesions. Sessile serrated polyps, but not all polyps, were reviewed.
      CONCLUSIONS: Individuals who coexpress sessile serrated polyps and conventional
      adenomas have an aggressive colorectal phenotype. They harbor larger sessile
      serrated polyps and more numerous and advanced adenomas than individuals with
      only sessile serrated polyps or adenomas. Synchronous colorectal cancers were
      found exclusively in cohorts with sessile serrated polyps. Individuals with
      sessile serrated polyps, especially with coexistent conventional adenomas, appear
      to be a high-risk group, which needs to be accounted for when calculating
      postpolypectomy surveillance intervals.

PMID- 21904136
TI  - Pathways of carcinogenesis are reflected in patterns of polyp pathology in
      patients screened for colorectal cancer.
AB  - BACKGROUND: There are multiple genetic routes to colorectal cancer, including
      chromosomal instability, mismatch repair dysfunction, and global
      hypermethylation. Few consider the possibility that multiple pathways are
      synchronously active. OBJECTIVE: This study was conducted to test the hypothesis
      that multiple synchronous carcinogenic pathways would result in an enhanced
      neoplastic phenotype. SETTING: This study took place during outpatient screening
      colonoscopy. PATIENTS: Patient were included who were undergoing colonoscopies
      for average and familial risk for colorectal cancer. DESIGN: Adenomas were
      evidence of chromosomal instability or DNA mismatch repair dysfunction, and
      serrated polyps of CpG island hypermethylation. Patients with 1 or 2 polyps were
      compared with those with >2 polyps, with polyps more than 10-mm diameter
      (advanced) as the end point. RESULTS: There were 1408 patients: 524 at average
      risk (41%) and 884 (59%) with a family history. Polyps were found in 47.7% of the
      average-risk patients and in 45.9% of patients with a family history. Adenoma
      detection rates were 33.8% and 30.4%, and serrated polyp detection rates were
      24.8% and 23.9%. There were more advanced polyps in all patients with >2 polyps
      than in those with 1 or 2 (36.2% vs 13.6%, P < .002), as well as in the subgroup
      of patients having average-risk screening (50% vs 11.1%, P < .001). Having a
      combination of >2 adenomas and serrated polyps in the same colon increased the
      risk of finding advanced polyps compared with adenomas or serrated polyps alone
      (serrated polyps, 12.7%; >2 adenomas, 17.7%; both, 27.1%; P = .02). LIMITATIONS:
      Serrated polyps were not subclassified by histology. CONCLUSION: Coexistence of
      serrated and adenomatous polyps reflects a colon prone to advanced polyps, and
      potentially cancer.

PMID- 21904137
TI  - Family history, surgery, and APC mutation are risk factors for desmoid tumors in
      familial adenomatous polyposis: an international cohort study.
AB  - BACKGROUND: Ability to identify patients with familial adenomatous polyposis who
      have a high risk of developing desmoid tumors may affect decisions in clinical
      practice. OBJECTIVES: Our aim was to assess several risk factors for desmoid
      tumor development in an international cohort of patients with familial
      adenomatous polyposis and to evaluate the clinical relevance of risk factors.
      DESIGN: This was a retrospective cohort study. SETTING AND PATIENTS: Polyposis
      registries in The Netherlands, France, Denmark, Finland, and Italy provided
      information on familial adenomatous polyposis patients with desmoid tumors. MAIN
      OUTCOME MEASURES: We used univariate and multivariable analyses of data from
      registries in The Netherlands, France, Denmark, and Finland to test whether
      gender, APC mutation site, previous colorectal surgery, colorectal cancer, and
      family history for desmoid tumors contribute to risk of developing desmoid tumors
      at any location, or specifically at an intra-abdominal location. The effect of
      family history was tested with a generalized linear mixed model. RESULTS: : Of
      2260 patients with familial adenomatous polyposis from 912 families in The
      Netherlands, France, Denmark, and Finland, 220 patients (10%) had desmoid tumors
      (101 men). In 387 patients with desmoid tumors (including 167 patients from the
      Italian registry), the median age at diagnosis of the first desmoid tumor was 31
      years (range, 4 months-74 years). Desmoid locations were intra-abdominal (53%),
      abdominal wall (24%), extremities (9%), and unknown sites or combinations of
      sites (14%). Multivariable analysis of risk factors for desmoids at any location
      showed surgery (OR, 2.58; P = .0004), an APC mutation 3' of codon 1444 (OR, 3.0;
      P < .0001), and a positive family history (P < .0001) to be independently
      associated with desmoid development. When only intra-abdominal location was
      analyzed, APC mutation site was not associated with desmoid development.
      LIMITATIONS: Selection bias may have occurred. CONCLUSIONS: A positive family
      history for desmoid tumors, abdominal surgery, and APC mutation site are
      significant risk factors for development of desmoid tumors. The results may have
      implications for determining the optimal management of FAP patients and guide
      future studies.

PMID- 21904138
TI  - Psychometric evaluation of a new patient-completed questionnaire for evaluating
      anal incontinence symptoms and impact on quality of life: the ICIQ-B.
AB  - BACKGROUND: A psychometrically robust patient-completed questionnaire for anal
      incontinence, which reflects issues of importance to both clinicians and
      patients, was lacking for assessment purposes. OBJECTIVE: This study aimed to
      determine the psychometric properties of a new questionnaire developed to address
      this need, the International Consultation on Incontinence Questionnaire-Bowels
      module. DESIGN: Qualitative studies were used to refine the developmental version
      of the questionnaire. Quantitative studies were conducted to evaluate its
      psychometric properties. SETTINGS: Patients were invited to complete the
      questionnaire via postal administration. PATIENTS: Two hundred sixty-one patients
      with known bowel symptoms participated in the study (244 females, 17 males; mean
      age, 59.7 years (range, 24-92)). MAIN OUTCOME MEASURES: The aspects of validity
      were evaluated in comparison with available evidence, responses to existing
      instruments, and physiological findings. Reliability was assessed through repeat
      administration of the questionnaire and evaluation of internal consistency by the
      Cronbach alpha coefficient. Responsiveness following treatment was evaluated by
      the use of the Wilcoxon signed rank test. Exploratory factor analysis was used to
      derive the final version of the questionnaire with evidence from the above
      studies. RESULTS: The final questionnaire contains 17 questions arranged in 3
      scored domains: bowel pattern, bowel control, and quality of life, with 4
      unscored items included to evaluate important issues from a clinical or patient
      perspective. The questionnaire demonstrated acceptable validity, "good" to "very
      good" reliability, and reasonable response to changes in symptom and quality-of
      life status following intervention. LIMITATIONS: Response rates varied according
      to location. CONCLUSIONS: The International Consultation on Incontinence
      Questionnaire Bowel module is a psychometrically robust, self-report instrument
      for the evaluation of anal incontinence and its impact on quality of life. It is
      suitable for use in individuals with anal incontinence of varying causes. It
      includes a scoring system for use in clinical practice and research.

PMID- 21904139
TI  - Timing of surgery following preoperative therapy in rectal cancer: the need for a
      prospective randomized trial?
AB  - BACKGROUND: In rectal cancer, the standard of care after the completion of
      radiotherapy is surgery at 6 to 8 weeks. However, there is variation regarding
      the timing of surgery. OBJECTIVE: This investigation aimed to audit the timing of
      surgery following radiotherapy and to compare perioperative morbidity and tumor
      downstaging in patients operated on, before and after the 6- to 8-week window.
      DESIGN: A retrospective review of rectal cancers treated preoperatively in our
      cancer network over a 27-month period. The effect of "time till surgery" of 6 to
      8 weeks, <6 weeks, and >8 weeks on T downstaging and nodal downstaging was
      calculated by univariate and multivariate logistic regression analyses. SETTING:
      This study was conducted in an oncology tertiary referral center in the Southwest
      London Cancer Network. PATIENTS: Patients receiving preoperative radiotherapy for
      primary locally advanced rectal cancer undergoing subsequent surgical resection
      were eligible. MAIN OUTCOME MEASURES: The primary outcome measurement was time to
      surgery following the completion of (chemo) radiotherapy. Thirty-day
      perioperative morbidity and mortality and tumor and nodal downstaging were
      examined according to the timing of surgery. LIMITATIONS: This study was limited
      by its nonrandomized retrospective design and the lack of standardization of
      preoperative chemotherapy. RESULTS: Thirty-two (34%) patients underwent surgery
      at 6 to 8 weeks, 45 (47%) at >8 weeks, and 18 (19%) at <6 weeks after
      radiotherapy. Delay was attributed to scheduling in 87% of cases and to
      comorbidities in the remainder. T downstaging occurred in 6 (33.3%) patients in
      the <6 weeks group, in 12 (37.5%) in the 6 to 8 weeks group, and in 28 (62.2%) in
      >8 weeks group with no significant differences in perioperative morbidity. On
      multivariate analysis, T downstaging was significantly greater for the >8 weeks
      group (OR, 3.79; 95% CI: 1.11-12.99; P = .03). More patients were staged ypT0-T2,
      19 of 45 (42%) in the >8 weeks group vs other groups, 14 of 50 (28%, P < .05).
      CONCLUSIONS: Following radiotherapy, surgery frequently occurs at >8 weeks and is
      associated with increased downstaging. The consequences on survival and
      perioperative morbidity warrant further investigation.

PMID- 21904140
TI  - Can a novel MRI staging system for low rectal cancer aid surgical planning?
AB  - BACKGROUND: Low rectal cancers are associated with worse outcomes in comparison
      with mid and upper rectal tumors. OBJECTIVE: This study aimed to assess the
      predictive accuracy of MRI in identifying the correct surgical approach based on
      the mesorectal and extralevator planes. DESIGN: This study involved the
      retrospective analysis of MRI and histopathology data of 33 patients with low
      rectal cancer, with the use of an anatomically based staging system. Three
      radiologists reported on the available surgical planes of excision based on the
      predicted relationship of tumor to key anatomical features. MRI-predicted planes
      of excision were then compared with the histopathological planes actually
      required, with the use of the same staging criteria. SETTINGS: The study was
      conducted at 4 English district general hospitals. PATIENTS: Unselected patients
      with low rectal cancer, all of whom were participants in a multicenter study,
      were eligible for this study. MAIN OUTCOME MEASURES: : The main outcome measured
      was the accuracy of operative plane prediction on MRI. RESULTS: : On pathological
      analysis, the mesorectal plane would have been sufficient to achieve a clear
      margin in 28 of 33 (84.9%) of cases. The extralevator plane was required in 5 of
      33 (15.1%). Planes were correctly predicted by MRI in 29 of 33 cases by
      radiologist 1 and 24 of 33 cases by radiologists 2 and 3 with an accuracy of
      87.9% and 72.7%. Overstaging (extralevator plane predicted when a mesorectal
      plane would have sufficed) occurred in 3 of 33 and 7 of 33 cases. Understaging
      (mesorectal plane predicted when an extralevator plane was required) occurred in
      1 of 33 and 2 of 33 cases. The positive and negative predictive values of MRI in
      determining the histopathological plane of excision required were 57% and 96% for
      radiologist 1 and 30% and 91% for radiologists 2 and 3. LIMITATIONS: This study
      was limited by its retrospective nature and its relatively small patient numbers.
      No account was taken of postoperative function when recommending the surgical
      plane. CONCLUSIONS: This supports an anatomically based MRI staging system for
      low rectal cancer to predict the planes of surgical excision. This may help to
      reduce margin positivity and to improve outcome in patients with low rectal
      cancer.

PMID- 21904141
TI  - Is colonoscopy still mandatory after a CT diagnosis of left-sided diverticulitis:
      can colorectal cancer be confidently excluded?
AB  - BACKGROUND: It is routine practice to perform colonoscopy as a follow-up after an
      attack of diverticulitis, with the main aim to exclude any underlying malignancy.
      PURPOSE: This study aimed to determine whether colonoscopy is necessary and what
      additional information is gained from this procedure. DESIGN: This is a study of
      a retrospective cohort. SETTINGS AND PATIENTS: From January 2003 to June 2009,
      patients in whom left-sided diverticulitis was diagnosed on CT scan were matched
      with colonoscopy reports within 1 year from the date of CT by the use of
      radiology and endoscopy databases. Patients who had colonoscopy within 1 year
      before the CT scan were excluded. The Western Australian Cancer Registry was
      cross-referenced to identify patients who subsequently received diagnoses of
      cancers for whom colonoscopy reports were unavailable. MAIN OUTCOME MEASURES: The
      main outcome measures were the number of patients in whom colorectal cancers were
      diagnosed and other incidental findings, eg, polyps, colitis, and stricture.
      RESULTS: Left-sided diverticulitis was diagnosed in 1088 patients on CT scan,
      whereas follow-up colonoscopy reports were available for 319 patients. Eighty-two
      (26%) patients had incidental findings of polyps (9 polyps >1 cm), and 9 patients
      (2.8%) received diagnoses of colorectal cancers on colonoscopy. After cross
      referencing with the cancer registry, the overall prevalence of colorectal cancer
      among the cohort within 1 year of CT scan was 2.1% (23 cases). The odds of a
      diagnosis of colorectal cancer were 6.7 times (95% CI 2.4-18.7) in patients with
      an abscess reported on CT, 4 times (95% CI 1.1-14.9) in patients with local
      perforation, and 18 times (95% CI 5.1-63.7) in patients with fistula compared
      with patients with uncomplicated diverticulitis. LIMITATIONS: This study was
      limited by the unavailability of data for private/interstate hospitals, and the
      relatively small number of cancer cases reduced the statistical power of the
      study. CONCLUSIONS: We recommend routine colonoscopy after an attack of presumed
      left-sided diverticulitis in patients who have not had recent colonic luminal
      evaluation. The rate of occult carcinoma is substantial in this patient
      population, in particular, when abscess, local perforation, and fistula are
      observed.

PMID- 21904142
TI  - Efficacy of sacral nerve stimulation for the treatment of fecal incontinence.
AB  - BACKGROUND: Sacral nerve stimulation has been shown to be an effective treatment
      for fecal incontinence and early studies reported success rates of 67% to 100%.
      However, "success" has been arbitrarily set at a 50% reduction in symptoms, and
      data are rarely reported with "intention to treat." OBJECTIVE: This study aimed
      to assess the true efficacy of sacral nerve stimulation for fecal incontinence
      compared with the published literature. DESIGN: This prospective 5-year study was
      conducted to assess 50 patients with fecal incontinence treated with sacral nerve
      stimulation. All analyses were performed on an intention-to-treat basis.
      SETTINGS: This study took place in a single tertiary referral colorectal
      department. PATIENTS: Fifty consecutive patients with fecal incontinence
      refractory to conservative management were included in the study. INTERVENTIONS:
      The interventions performed were temporary evaluation with or without permanent
      sacral nerve stimulation. MAIN OUTCOME MEASURES: : Primary outcome measures were
      1) attainment of continence, 2) reduction in fecal incontinence episodes, 3)
      improvement in Cleveland Clinic Fecal Incontinence scores, and 4) improvement in
      the ability to defer defecation. RESULTS: Thirteen patients (26%) did not respond
      at the temporary evaluation stage or were dissatisfied with the result. Ten
      further patients (20%) did not achieve a 50% reduction in symptoms following
      permanent implantation. The median follow-up was 17 months (range, 2-55), at
      which time 27 patients (54%) experienced a 50% or more reduction in symptoms,
      including 13 (26%) who achieved apparent continence. Median fecal incontinence
      episodes per fortnight reduced from 14 (range, 0-53) to 2 (range, 0-20; P <
      .0001). Median Cleveland Clinic Fecal Incontinence scores reduced from 15 (range,
      3-20) to 8 (range, 0-17; P < .0001). The ability to defer defecation improved
      significantly (P < .0001). These results compare favorably with the published
      literature. LIMITATIONS: Quality of life was not assessed. CONCLUSIONS: This
      study demonstrates that sacral nerve stimulation can be an effective treatment
      for patients with fecal incontinence; however, when analyzed by intention to
      treat, the symptoms of fecal incontinence continue in the majority (74%) of
      patients.

PMID- 21904143
TI  - Long-term results of fibrin glue treatment for cryptogenic perianal fistulas: a
      multicenter study.
AB  - BACKGROUND: Instillation of fibrin glue, a simple and safe procedure, has been
      shown to have a moderate short-term success rate in the treatment of cryptogenic
      perianal fistulas. OBJECTIVE: This study aimed to assess the long-term outcome of
      this procedure. DESIGN: This study included a retrospective chart review and
      telephone interviews. SETTINGS: This study was conducted at 4 university
      affiliated medical centers. PATIENTS: Patients were included who underwent fibrin
      glue instillation for complex cryptogenic fistula between 2002 and 2003 within a
      prospective trial and had successful healing. INTERVENTIONS: Fibrin glue was
      instilled for complex cryptogenic fistula. MAIN OUTCOME MEASURES: The main
      outcome measure was long-term fistula healing. RESULTS: Sixty patients
      participated in the initial trial; the fistulas in 32 of these patients were
      healed at 6 months. We have located and interviewed 23 (72%) of those patients.
      Seventeen (74%) patients remained disease free at a mean follow-up of 6.5 years.
      Six (26%) patients had variable degrees of recurrence; 4 needed further surgical
      intervention and 2 were treated with antibiotics only. Recurrent disease occurred
      at an average of 4.1 years (range, 11 mo to 6 y) from surgery, and on several
      occasions was at a different location in the perianal region. None of the
      patients experienced incontinence following the procedure. LIMITATIONS: The
      retrospective nature of this long-term follow-up was a limitation. Twenty-eight
      percent of the potentially eligible patients were lost to long-term follow-up.
      CONCLUSIONS: Short-term success of fibrin glue in the treatment of cryptogenic
      perianal fistula is predictive of long-term healing, but a quarter of those
      healed in the short term may develop recurrent symptoms in the long run.
      Injection of fibrin glue remains a safe and simple procedure and may preclude
      extensive surgery.

PMID- 21904144
TI  - Long-term follow-up of infrared coagulator ablation of anal high-grade dysplasia
      in men who have sex with men.
AB  - BACKGROUND: We previously reported on infrared coagulator ablation of anal high
      grade intraepithelial squamous lesions in HIV-positive and HIV-negative men who
      have sex with men (MSM) with a median follow-up of 1.5 years. OBJECTIVE: We
      sought to determine high-grade intraepithelial squamous lesion recurrence rates
      after long-term follow-up for infrared coagulator ablation, and whether patients
      progressed to invasive cancer. DESIGN: : This study investigated a retrospective
      cohort. SETTING: This study was set in an office-based practice. PATIENTS: The
      patients evaluated were MSM who underwent at least 1 infrared coagulator anal
      high-grade intraepithelial squamous lesion ablation between 1999 and 2005 with at
      least 1-year additional follow-up. INTERVENTION: Infrared coagulator ablation had
      been performed. MAIN OUTCOME MEASUREMENT: The primary outcomes measured were high
      grade intraepithelial squamous lesion recurrence and progression to anal squamous
      cell carcinoma. RESULTS: Ninety-six MSM were included (44 HIV-positive) with a
      median follow-up of 48 and 69 months in HIV-negative and HIV-positive MSM. Thiry
      five percent of HIV-positive and 31% of HIV-negative subjects from the original
      cohort were lost to follow-up. In HIV-negative MSM, 32 (62%) had a recurrence in
      a mean of 14 months. Recurrence rates after the second and third treatments were
      48% and 57%. In HIV-positive MSM, 40 (91%) had a recurrence in a mean of 17
      months. Recurrence rates after the second, third, and fourth infrared coagulator
      ablations were 63%, 85%, and 47%. After the first ablation, HIV-positive MSM were
      1.9 times more likely to have a recurrence than HIV-negative MSM (P = .009). One
      year after the first ablation, 61% of HIV-positive MSM had recurrent high-grade
      intraepithelial squamous lesions in comparison with 38% of HIV-negative MSM. One
      year after the second ablation, 49% of HIV-positive MSM had recurrent high-grade
      intraepithelial squamous lesions in comparison with 28% of HIV-negative MSM. In
      HIV-negative and HIV-positive MSM, the probability of curing an individual lesion
      after first ablation was 80% and 67%. Most recurrence was due to the development
      of metachronous lesions occurring in 82% and 52% of HIV-positive and HIV-negative
      subjects after their first infrared coagulator treatment. The mean number of
      recurrent lesions for both HIV-positive and HIV-negative MSM was never >2. No MSM
      developed squamous-cell carcinoma, and there were no serious adverse events. At
      last visit, 82% of HIV-positive MSM and 90% of HIV-negative MSM were high-grade
      intraepithelial squamous lesion free. LIMITATIONS: This was a retrospective,
      observational study with significant loss to follow-up. CONCLUSIONS: Infrared
      coagulator ablation is an effective treatment for high-grade intraepithelial
      squamous lesions, and no patients progressed to cancer. HIV-positive patients are
      significantly more likely to have a recurrence, and recurrence occurred more
      rapidly in these patients. Continued follow-up is important.

PMID- 21904145
TI  - Evaluation of modified estimation of physiologic ability and surgical stress in
      colorectal carcinoma surgery.
AB  - BACKGROUND: We recently modified Estimation of Physiologic Ability and Surgical
      Stress, our prediction scoring system. OBJECTIVE: This study evaluated the
      usefulness of our modified version for colorectal carcinoma in comparison with
      existing models. DESIGN: This investigation studied a multicenter cohort.
      SETTINGS: The study was conducted in regional referral hospitals in Japan.
      PATIENTS: Patients were included who underwent elective surgery for colorectal
      carcinoma. MAIN OUTCOME MEASURES: Postoperative morbidity, mortality, and
      predicted mortality rates for original and modified Estimation of Physiologic
      Ability and Surgical Stress were investigated in 2388 patients in comparison with
      existing European models. RESULTS: Among the models, the modified Estimation of
      Physiologic Ability and Surgical Stress demonstrated the highest discriminatory
      power in terms of in-hospital mortality (area under receiver operating
      characteristic curve: 0.84 for Estimation of Physiologic Ability and Surgical
      Stress, 0.87 for modified Estimation of Physiologic Ability and Surgical Stress,
      0.84 for Portsmouth modification of POSSUM, 0.74 for ASA status-based model), as
      well as 30-day mortality (area under receiver operating characteristic curve:
      0.82 for Estimation of Physiologic Ability and Surgical Stress, 0.84 for modified
      Estimation of Physiologic Ability and Surgical Stress, 0.81 for POSSUM, 0.78 for
      colorectal POSSUM, 0.76 for Association of Coloproctology of Great Britain and
      Ireland score). British models, in general, overpredicted postoperative mortality
      rates by more than 10 times. LIMITATIONS: The current study analyzed only the
      Japanese population treated in medium-volume centers. CONCLUSIONS: Among the
      models, modified Estimation of Physiologic Ability and Surgical Stress was the
      most accurate in predicting postoperative mortality in colorectal carcinoma
      surgery. These findings should be validated in Western populations, because the
      Japanese population may differ from Western populations in terms of body shape or
      reserve capacity.

PMID- 21904146
TI  - Risk-adjusted colon and rectal cancer incidence rates in the United States.
AB  - BACKGROUND: Population-based cancer incidence rates that adjust for multiple
      cancer primaries and for prevalent cases of the disease provide a better
      approximation of risk. DESIGN: This study is based on a retrospective cohort.
      SETTING/PATIENTS: Included in the study were 9 original Surveillance,
      Epidemiology and End Results registries focusing on white and black males and
      females from 2000 through 2007. MAIN OUTCOME MEASURE: The main outcome measured
      was malignant colorectal cancer. RESULTS: Conventional colorectal cancer
      incidence rates overestimate population risk by 3.6% for white males, 4.0% for
      black males, 3.4% for white females, and 3.3% for black females. The level of
      overestimation bias remained similar across the age span for white and black
      males. However, for white females, rates were overestimated by 2.1% for ages 30
      to 39 and increased to 3.8% for ages 80 years and older. Corresponding values for
      black females were 1.5% and 3.8%. The trends in conventional rates were generally
      similar to the trends in risk-adjusted incidence rates, increasing or stable
      before age 50, but decreasing thereafter. The number of colorectal cancer cases
      in the United States is estimated from conventional incidence rates. In 2007, the
      number of colorectal cases was 59,599 for white males, 7,670 for black males,
      58,972 for white females, and 8,786 for black females. The number of colorectal
      cancer cases based on prevalence-corrected incidence rates increased by 2.2% for
      white males, 1.5% for black males, 2.1% for white females, and 1.5% for black
      females. CONCLUSION: Colorectal cancer incidence rates that include second and
      later colorectal cancer primaries and adjust for prevalence better reflect cancer
      burden, whereas colorectal cancer incidence rates that only include the first
      diagnosed case and adjust for prevalence better reflect cancer risk.

PMID- 21904147
TI  - Learning curve associated with colorectal endoscopic submucosal dissection for
      endoscopists experienced in gastric endoscopic submucosal dissection.
AB  - BACKGROUND: Colorectal endoscopic submucosal dissection requires a high level of
      skill and experience in therapeutic endoscopy because of the high risk of
      complications such as perforation and bleeding. Greater understanding of the
      procedural learning curve is required to standardize training and to achieve
      wider acceptance of this procedure. OBJECTIVE: The aims of this study were to
      evaluate the clinical outcomes of colorectal endoscopic submucosal dissection and
      to clarify its learning curve for endoscopists. DESIGN: We retrospectively
      reviewed the clinical outcomes for consecutive patients with colorectal neoplasms
      who underwent endoscopic submucosal dissection by 2 trainees under the guidance
      of experienced specialists. SETTING: The study was performed at the National
      Cancer Center Hospital, Tokyo, Japan. PATIENTS: Colorectal endoscopic submucosal
      dissections were performed for 101 consecutive patients with 102 colorectal
      neoplasms between April 2008 and December 2010. MAIN OUTCOME MEASURES: Procedure
      time, en bloc resection rate, completion rate, and complications were
      retrospectively compared between 4 training periods in which each trainee
      performed 10 endoscopic submucosal dissections per period and a final training
      period in which the trainees performed 10 to 12 endoscopic submucosal dissections
      to analyze the skill improvement with time. RESULTS: The procedure time and en
      bloc resection rate were not significantly different among the training periods.
      However, the completion rates in the fourth (100%) and fifth (95.5%) training
      periods (>= 31 cases/trainee) were significantly higher (P < .001) than those in
      the first (45%), second (70%), and third (80%) training periods (1-30
      cases/trainee). Two cases of perforation occurred during the study. LIMITATIONS:
      Limitations include the single-center design. Training programs and instruments
      vary with institution, which could affect the learning curve. CONCLUSIONS:
      Trainee endoscopists are able to perform colorectal endoscopic submucosal
      dissection without serious complications under the guidance of experienced
      specialists. They can perform it safely and independently after preparatory
      training and experience with >= 30 cases.

PMID- 21904148
TI  - Laparoscopic rectosigmoid resection with transanal colonic pull-through and
      delayed coloanal anastomosis: a new approach to adult Hirschsprung disease.
AB  - BACKGROUND: Hirschsprung disease in adults is a rare and frequently misdiagnosed
      cause of long-standing, refractory constipation. Surgical procedures initially
      developed for pediatric patients have been applied to adults with varying degrees
      of success. OBJECTIVE: Our aim was to describe a new surgical procedure
      consisting of laparoscopic rectosigmoid resection with a transanal colonic pull
      through followed by a delayed coloanal anastomosis for the treatment of
      Hirschsprung disease in adults and to present our preliminary results with this
      technique. DESIGN AND SETTING: This was a descriptive observational study of
      treatment outcome conducted at the colorectal surgical unit of a university
      teaching hospital in France. PATIENTS: Patients were adults with confirmed
      Hirschsprung disease treated from October 2006 through February 2009.
      INTERVENTION: Laparoscopic rectosigmoid resection was performed with a transanal
      colonic pull-through followed by a delayed coloanal anastomosis. MAIN OUTCOME
      MEASURES: Clinical and functional data (Cleveland Clinic Florida incontinence
      scale and Fecal Incontinence Quality of Life scale) were obtained at
      postoperative visits. RESULTS: Five patients underwent the procedure. One patient
      died of postoperative cardiovascular complications. No patient had to be
      reoperated. No anastomotic leakage occurred. One patient developed anastomotic
      stricture requiring dilatation. No sexual or urinary dysfunction was reported.
      Postoperative analysis (mean follow-up 16 months) showed good functional outcomes
      in 3 (75%) of the 4 evaluable patients. LIMITATIONS: This study had only a small
      number of patients and no controls other comparison with cases reported in the
      literature. CONCLUSION: Laparoscopic rectosigmoid resection with a transanal
      colonic pull-through followed by delayed coloanal anastomosis represents a valid
      alternative in the treatment of Hirschsprung disease in adult patients, because
      it involves minimally invasive surgery, does not require a preventive diverting
      stoma, and shows anastomotic security.

PMID- 21904149
TI  - Robotic cylindrical abdominoperineal resection with transabdominal levator
      transection.
AB  - PURPOSE: The extralevator approach to abdominoperineal resection is an emerging
      surgical option for patients with low rectal cancer. This technique involves a
      wide excision of the levator muscles that could reduce the high incidence of
      circumferential margin positivity associated with conventional abdominoperineal
      resections. We present our technique of robotic cylindrical abdominoperineal
      resection where the daVinci robot is used to perform a controlled transection of
      the levator muscles transabdominally under direct visualization. METHODS: Five
      patients with rectal adenocarcinoma within 5 cm of the anal verge underwent robot
      assisted cylindrical abdominoperineal resection. Safety, feasibility, immediate
      postoperative outcomes, and pathological adequacy of the specimen were assessed.
      RESULTS: The procedure was successfully completed in all 5 patients without any
      intraoperative complications, robot-associated morbidity, or conversion to the
      open approach. The mean operative time and length of hospital stay were 343
      minutes and 5.8 days. An intact mesorectal envelope and negative circumferential
      margin was achieved in all cases. All specimens had a cylindrical shape.
      CONCLUSIONS: Robotic assistance enables the transabdominal transection of the
      levator muscles in cylindrical abdominoperineal resection, with acceptable
      perioperative and pathological outcomes. Further studies are essential to
      objectively define the safety, efficacy, and long-term results of this new
      technique.

PMID- 21904151
TI  - J-curve for DBP and cardiovascular mortality in coronary artery disease patients:
      myth or reality.

PMID- 21904150
TI  - Treatment of diverticular disease of the colon and prevention of acute
      diverticulitis: a systematic review.
AB  - BACKGROUND: Diverticular disease of the colon is a common disorder, characterized
      by recurrent symptoms and complications such as diverticulitis, requiring
      hospital admissions and surgery. OBJECTIVE: This study aimed to systematically
      review the evidence for medical therapy of diverticular disease in reducing
      symptoms and preventing acute diverticulitis. DATA SOURCES: MEDLINE and Embase
      databases (1966 to February 2010). STUDY SELECTION: The studies selected were
      prospective clinical trials on uncomplicated diverticular disease of the colon.
      INTERVENTIONS: Four investigators independently reviewed articles, extracted
      data, and assessed study quality according to standardized criteria. MAIN OUTCOME
      MEASURES: The main outcomes measured were improvement in symptoms, complete
      remission of symptoms, and prevention of acute diverticulitis. RESULTS: We
      identified 31 studies, including 6 placebo-controlled trials. The methodological
      quality of these studies was suboptimal. Only 10 trials provided a detailed
      description of the patient history, 8 assessed symptoms by the use of a validated
      questionnaire, and 14 appropriately defined inclusion and exclusion criteria.
      Only one long-term double-blind placebo-controlled study was identified. This
      reported a significant improvement in symptoms and greater prevalence of symptom
      free patients at 1 year with fiber plus rifaximin in comparison with fiber alone.
      The efficacy of treatment in preventing acute diverticulitis was evaluated in 11
      randomized trials. Four trials compared rifaximin plus fiber vs fiber alone and
      failed to show a significant difference between treatments. However, cumulative
      data from these trials revealed a significant benefit following rifaximin and
      fiber (1-year rate of acute diverticulitis: 11/970 (1.1%) vs 20/690 (2.9%); P =
      .012), but with a number needed to treat of 57, to prevent an attack of acute
      diverticulitis. LIMITATIONS: : Heterogeneity of the study design, patients'
      characteristics, regimens and combination of studied treatment, and outcome
      reporting precluded the pooling of results and limited interpretation.
      CONCLUSIONS: The treatment for diverticular disease relies mainly on data from
      uncontrolled studies. Treatment showed some evidence of improvement in symptoms,
      but its role in the prevention of acute diverticulitis remains to be defined.

PMID- 21904152
TI  - The renin-angiotensin system: new horizons.

PMID- 21904153
TI  - To PRESERVE and protect: targeting the microcirculation in prevention of diabetes
      and its complications.

PMID- 21904154
TI  - Resistance to antihypertensive treatment: reality or artifact of reasoning?

PMID- 21904155
TI  - Measurement of central aortic pressure: an acceptable compromise?

PMID- 21904156
TI  - A simple test to appreciate compliance to aliskiren treatment.

PMID- 21904159
TI  - Hidden sodium in Mediterranean food.

PMID- 21904160
TI  - Use of oral contraceptives and arterial stiffness.

PMID- 21904164
TI  - Sleep curtailment and workers' productivity: shouldn't the ballgames end by 10
      PM.

PMID- 21904165
TI  - 9/11 and occupational/environmental medicine.

PMID- 21904166
TI  - JOEM bibliography of articles related to the events of September 11, 2001.

PMID- 21904167
TI  - What is the Finnish model of work ability?

PMID- 21904170
TI  - Modern perspectives of open reduction and plate fixation of proximal humerus
      fractures.
AB  - Recent innovations have greatly increased the range of proximal humeral fractures
      that are amenable to open reduction and plate fixation.The optimum technique for
      some of the more complex fracture patterns is not yet fully refined.This article
      aims to describe the recent advances in the treatment of complex proximal humeral
      fractures by open reduction and locking plate fixation, focusing particularly on
      the indications for surgery, the operative techniques, and the expected outcomes
      after treatment.

PMID- 21904171
TI  - Vision loss after inadvertent corneal perforation during lid anesthesia.
AB  - A 68-year-old woman was referred for glaucoma management after inadvertent
      corneal perforation during eyelid anesthesia for upper eyelid blepharoplasty. A
      mixture of 50:50 2% lidocaine with 1:100,000 epinephrine and 0.5% bupivacaine
      buffered with sodium bicarbonate was injected intracamerally. Decreased vision
      and uncontrollable intraocular pressure resulted, despite prompt anterior chamber
      washout. Examination showed corneal edema, inflammation, and secondary angle
      closure. Intraocular pressure control with seton placement led to an improvement
      in vision; however, mild corneal haze remained, and specular microscopy showed
      endothelial cell loss, presumably secondary to local anesthetic toxicity.
      Inadvertent ocular penetration is a rare but serious complication of local eyelid
      anesthesia. Prompt recognition is essential to institute appropriate management
      and minimize subsequent vision loss.

PMID- 21904172
TI  - Nasal fat preservation in upper eyelid blepharoplasty.
AB  - INTRODUCTION: Traditional upper blepharoplasty is a subtractive form of surgery
      that involves the excision of variable amounts of skin, muscle, and fat from the
      eyelid. The goal of surgery is to improve field of vision and/or appearance.
      While surgical debulking of the eyelid may improve appearance early on, the
      volume loss inherent to this process (especially fat excision) can contribute to
      a hollowed appearance with an associated deep and sunken superior sulcus. This
      skeletonized look may be mitigated by repositioning a prominent nasal fat pad, if
      present, to the central upper eyelid. METHODS: The charts of patients who
      underwent upper blepharoplasty with repositioning of the nasal fat pad (as
      described in this manuscript) to the central arcus marginalis of the superior
      orbital rim during surgery were reviewed. Patients with a history of previous
      eyelid surgery or trauma or who had concurrent ptosis or other eyelid
      malpositions were excluded from the study. Also excluded were patients who did
      not manifest prominent nasal fat pads at surgery. Postoperative interval follow
      up was consistent until 6 months after surgery and more sporadic thereafter, as
      patients more frequently missed appointments. Postoperative healing issues,
      patient complaints, complications, and subjective physician and patient
      satisfaction assessments were noted. Final results were gauged on each patient's
      final visit after surgery. RESULTS: Seventy-six patients were included in the
      study. Forty-eight patients (63%) were women, and 28 patients (37%) were men. The
      surgical procedure was uneventful in all patients. The average patient age was 66
      years and the mean follow up was 11 months (range 6-22 months). There was one
      case of postoperative pseudo-Brown syndrome, which resolved with steroid
      injections. There were 2 cases of postoperative presumed mechanical ptosis, early
      in the series, lasting for 2 weeks, which in both cases responded to oral
      steroids. Subjectively, there was no new or worsening superior sulcus hollowness
      observed by patient or surgeon at last follow up in all cases. CONCLUSIONS:
      Volume loss and the value of fat preservation in lower blepharoplasty are well
      documented and accepted among eyelid surgeons. The affect of iatrogenic volume
      depletion in upper eyelid blepharoplasty, while understood, has gained less
      attention. Repositioning the prominent nasal fat pad of the upper eyelid to the
      central sulcus adds little time to surgery, allows preservation of upper eyelid
      fat during surgery, and may be a useful adjunct to the upper blepharoplasty
      surgeon. While further studies are needed to more critically assess eyelid
      volumetric changes, this technique holds promise as a preventative measure for
      superior sulcus hollowing after surgery.

PMID- 21904174
TI  - Re: "comparison of the exposure rate of wrapped hydroxyapatite (Bio-Eye) versus
      unwrapped porous polyethylene (Medpor) orbital implants in enucleated patients".

PMID- 21904175
TI  - Re: "propranolol for the treatment of orbital infantile hemangiomas".

PMID- 21904177
TI  - Re: "a case of bilateral silent sinus syndrome presenting with chronic ocular
      surface disease".

PMID- 21904179
TI  - Re:"intubation of the ostium and nasolacrimal duct with a single self-linking
      silicone stent in external dacryocystorhinostomy".

PMID- 21904180
TI  - Re: "intubation of the ostium and nasolacrimal duct with a single self-linking
      silicone stent in external dacryocystorhinostomy".

PMID- 21904183
TI  - Punctoplasty with a Kelly punch.

PMID- 21904184
TI  - Asphyxiation due to ocular prosthesis ingestion.

PMID- 21904185
TI  - A prescription for disruptions in care: community building among nurses to
      address horizontal violence.
AB  - In the health care environment, threats exist that can impact a nurse's ability
      to provide safe, quality care. One of these threats is disruptive behavior among
      health care workers in which negative interactions adversely affect communication
      and collaboration. When this occurs among nurses, it is identified as horizontal
      violence. An underlying concept is power. When attempting to address these
      behaviors in the workplace, it is important that nurses recognize the context in
      which they occur so sustaining changes can be made. Community building among
      nurses may be an appropriate approach to give nurses the skills to make these
      changes.

PMID- 21904186
TI  - Food insecurity is associated with morbidity and patterns of healthcare
      utilization among HIV-infected individuals in a resource-poor setting.
AB  - OBJECTIVE: We undertook a longitudinal study in rural Uganda to understand the
      association of food insecurity with morbidity and patterns of healthcare
      utilization among HIV-infected individuals enrolled in an antiretroviral therapy
      program. DESIGN: Longitudinal cohort study. METHODS: Participants were enrolled
      from the Uganda AIDS Rural Treatment Outcomes cohort, and underwent quarterly
      structured interviews and blood draws. The primary predictor was food insecurity
      measured by the validated Household Food Insecurity Access Scale. Primary
      outcomes included health-related quality of life measured by the validated
      Medical Outcomes Study-HIV Physical Health Summary (PHS), incident self-reported
      opportunistic infections, number of hospitalizations, and missed clinic visits.
      To estimate model parameters, we used the method of generalized estimating
      equations, adjusting for sociodemographic and clinical variables. Explanatory
      variables were lagged by 3 months to strengthen causal interpretations. RESULTS:
      Beginning in May 2007, 458 persons were followed for a median of 2.07 years, and
      40% were severely food insecure at baseline. Severe food insecurity was
      associated with worse PHS, opportunistic infections, and increased
      hospitalizations (results were similar in concurrent and lagged models).
      Mild/moderate food insecurity was associated with missed clinic visits in
      concurrent models, whereas in lagged models, severe food insecurity was
      associated with reduced odds of missed clinic visits. CONCLUSION: Based on the
      negative impact of food insecurity on morbidity and patterns of healthcare
      utilization among HIV-infected individuals, policies and programs that address
      food insecurity should be a critical component of HIV treatment programs
      worldwide.

PMID- 21904187
TI  - Dynamics of gag-pol minority viral populations in naive HIV-1-infected patients
      failing protease inhibitor regimen.
AB  - OBJECTIVE: Recently, we have reported the role of baseline gag cleavage site
      mutations on the virological outcome of a dual-boosted protease inhibitor regimen
      in antiretroviral-naive patients (2IP-ANRS 127 trial). The objective of this
      substudy was to characterize, in patients experiencing virological failure, from
      the 2IP-ANRS 127 trial, the viral quasispecies present at baseline and at
      virological failure in gag cleavage site, in gag-pol frameshift and in protease
      coding region. METHODS: In four patients, we analysed by clonal analysis the
      viral population in gag cleavage site (p17/p24, p24/p2, p2/p7, p7/p1,
      p1/p6(gag)), in p6(gag), in gag-pol frameshift [p1/transframe protein
      (TFP)/p6(pol)] and in protease-coding region. RESULTS: Clonal analysis of
      protease-coding region failed to detect major as well as minor protease inhibitor
      resistance-associated mutations in all four patients. In one patient, a I15V
      mutated variant increased from 13 to 100% between baseline and week 24. Clonal
      analysis of gag and gag-pol cleavage site showed an increase in specific viral
      populations in p2/p7 cleavage site between baseline and virological failure in
      three patients. Among them, we described in one patient, that the predominant
      population at virological failure harboured in p2/p7 and TFP/p6(pol)-specific
      genotypic profiles associated with duplication of the P(T)APP motif in p6(gag)
      and the I15V protease mutation on the same individual molecular clones.
      CONCLUSION: We highlighted the emergence of minority viral populations in the
      p2/p7 cleavage site between baseline and virological failure. In addition, we
      showed the association of a specific protease mutation with gag and gag-pol
      cleavage site substitutions, suggesting their possible role in virological
      outcome.

PMID- 21904188
TI  - Effects of low-intensity pulsed ultrasound therapy on fracture healing: a
      systematic review and meta-analysis.
AB  - OBJECTIVE: This systematic review and meta-analysis was performed to identify the
      clinical trials relevant to the effects of low-intensity pulsed ultrasound
      (LIPUS) on bone regeneration. DESIGN: We searched five international electronic
      databases including MEDLINE (1966-June 2010), and PubMed, EMBase, Cumulative
      Index to Nursing and Allied Health, and Cochrane (1980-June 2010) to identify the
      relevant studies on the effects of LIPUS on bone healing. The inclusion criteria
      were human clinical trial, all types of bones, fractures, and outcome
      measurements, LIPUS application, and English language. Overall, 260 potentially
      eligible abstracts were identified, and 65 articles were retrieved in full text.
      Of the 65 studies, 23 met the inclusion criteria and were critically appraised by
      two raters independently using the PEDro quality measurement method. The results
      of all eligible studies were categorized in three groups: fresh fractures,
      delayed or nonunions, and distraction osteogenesis. Seven trials among fresh
      fracture trials were identified eligible for meta-analysis because of the
      varieties of outcome measurements and clinical situations. The time of the third
      cortical bridging (increase in density or size of initial periosteal reaction) in
      radiographic healing was our common criteria for the meta-analysis. RESULTS: The
      time of third cortical bridging was statistically earlier following LIPUS therapy
      in fresh fractures (mean random effect, 2.263; 95% CI, 0.183-4.343, P = 0.033).
      CONCLUSIONS: LIPUS can stimulate radiographic bone healing in fresh fractures.
      Although there is weak evidence that LIPUS also supports radiographic healing in
      delayed unions and nonunions, it was not possible to pool the data because of a
      paucity of sufficient studies with similar outcome measures.

PMID- 21904189
TI  - Axial low back pain in a patient with a 'mouse face sign' on bone scan.

PMID- 21904190
TI  - Diastematomyelia presenting in adulthood as back pain.

PMID- 21904191
TI  - Intramuscular hemangioma of flexor digitorum brevis muscle.

PMID- 21904192
TI  - Motor factors associated with health-related quality-of-life in ambulatory
      children with cerebral palsy.
AB  - OBJECTIVE: This study aimed to examine the relationship between fine and gross
      motor skills and cerebral palsy-specific quality-of-life in ambulatory children
      with cerebral palsy. DESIGN: Thirty-nine children with cerebral palsy (29 boys,
      10 girls; mean age +/- SD, 8.8 +/- 2.3 yrs) classified under Gross Motor Function
      Classification System Level I or II were enrolled. Health-related quality-of-life
      was evaluated using the Cerebral Palsy Quality of Life Questionnaire for Children
      (parent-proxy version). Motor functions were measured using the Bruininks
      Oseretsky Test of Motor Proficiency. RESULTS: Regression analysis for QOL
      revealed fine motor skills, including upper-limb speed and dexterity, which are
      positively correlated to functioning (r = 0.205, P < 0.01), and visual-motor
      control that is positively correlated to other domains, including social well
      being and acceptance, participation and physical health, emotional well-being and
      self-esteem, and family health (r = 0.150-0.188, P < 0.05). CONCLUSIONS: Fine
      motor functions, including upper-limb speed and dexterity and visual-motor
      control, were the most important motor factors associated with health-related
      quality-of-life in ambulatory children with cerebral palsy.

PMID- 21904193
TI  - Bilateral congenital undescended scapula (sprengel deformity).

PMID- 21904195
TI  - Biological mitral valve prosthesis in a patient supported with a permanent left
      ventricle assist device.
AB  - Mitral valve pathology, especially status postvalve replacement (biological or
      mechanical), remains challenging in patients suffering from end-stage heart
      failure and undergoing left ventricular assist device (LVAD) placement due to
      several factors (potential source for thromboembolic complications, risk for
      structural deterioration of the biological prosthesis leading to stenosis, and
      inadequate LVAD preload). We report a case of long-term LVAD support in a patient
      with a previously implanted biological mitral valve prosthesis. During LVAD
      insertion, the valve was left in place, and it functioned well until the death of
      the patient 3 years later. The patient remained free of any valve-related
      complications.

PMID- 21904194
TI  - Intrathecal bupivacaine in comparison with a combination of nalbuphine and
      bupivacaine for subarachnoid block: a randomized prospective double-blind
      clinical study.
AB  - We performed this randomized, prospective double-blind study to evaluate the
      effects of 2 different doses of intrathecal nalbuphine (a synthetic opioid
      agonist-antagonist) on the onset, duration of action, side effects, and
      complication produced by intrathecal hyperbaric 0.5% bupivacaine in lower
      abdominal, urologic and lower limb surgeries. Seventy-five patients of ASA grades
      1 and 2 of either sex in the age group of 20-60 years were randomly allocated to
      1 of 3 groups. Group A (n = 25) received 2.5 mL of 0.5% hyperbaric bupivacaine +
      1 mL sterile water intrathecally; group B (n = 25) received 2.5 mL of 0.5%
      hyperbaric bupivacaine + 1 mL (200 MUg) nalbuphine intrathecally; group C (n =
      25) received 2.5 mL of 0.5% hyperbaric bupivacaine + 1 mL (400 MUg) nalbuphine
      intrathecally. The onsets of sensory and motor blockade, highest level of sensory
      blockade, 2 segment regression time of sensory blockade, duration of motor
      blockade and analgesia, visual analog scale score, hemodynamic and respiratory
      changes, side effects were recorded, tabulated, and analyzed. Onsets of sensory
      and motor blockade and duration of motor blockade were not affected. Two segment
      regression time of sensory blockade and duration of analgesia were maximally
      prolonged in group C (P < 0.05). The visual analog scale scores were in the
      following order: group A > group B > group C at 90, 120, and 150 minutes after
      induction (P < 0.05). Hemodynamic and respiratory complications were absent
      except in 2 patients in groups A and C each, and 1 patient in group B developed
      bradycardia (P > 0.05). One patient in group A had nausea and vomiting, 2
      patients in each group developed shivering (P > 0.05). No other side effect or
      complication was observed. Nalbuphine hydrochloride (400 MUg) significantly
      prolongs the duration of sensory blockade and postoperative analgesia without any
      side effect or complication when introduced intrathecally along with hyperbaric
      bupivacaine. 

PMID- 21904196
TI  - Enhanced cortisol increase upon awakening is associated with greater pain ratings
      but not salivary cortisol or soluble tumor necrosis factor-alpha receptor II
      responses to acute pain.
AB  - OBJECTIVES: The cortisol awakening response (CAR) is related to psychosocial
      factors and health in potentially significant ways, suggesting that it may be a
      distinctive marker of hypothalamic-pituitary-adrenal axis function and
      dysfunction. This study sought to expand upon previous work that examined the
      association between CAR and ratings of laboratory-evoked acute pain stimulation.
      In addition to evoked pain ratings, this study also tested whether CAR was
      prospectively related with salivary cortisol and soluble tumor necrosis factor
      alpha receptor II responses to acute pain stimulation. METHODS: This study
      included 36 healthy, pain-free volunteers of both sexes recruited through posted
      study flyers. Prior to completion of laboratory pain testing, salivary cortisol
      samples were obtained at home over the course of a single morning according to
      the following time frame: upon awakening, and 15, 30, and 60 minute after
      awakening. After collection of saliva, study participants brought their home
      saliva samples to the laboratory for assay and subsequently completed acute
      experimental pain testing procedures. RESULTS: Cluster analysis of CAR revealed
      two distinct groups with similar patterns of cortisol response to awakening;
      increased and flattened. Relative to flattened CAR, increased CAR was associated
      with greater ratings of pain intensity and unpleasantness. Salivary cortisol was
      significantly increased and soluble tumor necrosis factor-alpha receptor II
      significantly decreased after pain testing, but neither of these responses
      differed as a function of increased versus flattened CAR. DISCUSSION: CAR may be
      a marker for stress sensitivity and/or the anticipation of impending stress,
      which could explain why the increased CAR cohort reported greater acute pain
      ratings.

PMID- 21904197
TI  - Addressing parental concerns about pain during childhood vaccination: is there
      enough time to include pain management in the ambulatory setting?
AB  - OBJECTIVE: Pain from vaccine injections remains undertreated, despite the
      availability of numerous pain-relieving strategies. Healthcare providers report
      lack of time within current office workflows as a major barrier to routine pain
      management. The objective was to document the total time involved in outpatient
      vaccine appointments to test the hypothesis that offering pain-relieving
      strategies can be practically implemented when considering the element of time to
      vaccine injection. PATIENTS AND METHODS: Prospective naturalistic study in 8
      urban outpatient primary care clinics (4 pediatric and 4 family practice) in
      Toronto. For 48 to 59 consecutive childhood vaccination appointments at each
      site, child waiting time from clinic arrival until first vaccine injection was
      tracked. RESULTS: Altogether, 405 vaccine appointments were included. The median
      age of the child undergoing vaccination was 12 months. The mean (SD) time from
      clinic arrival until first vaccine injection was 41.6 minutes (20.9), with a
      range of 7 to 132 minutes. Linear regression identified a significant (P<0.05)
      difference according to clinic [ranging from 19.4 min (6.5) to 57.5 min (20.2)]
      and number of family members in the appointment [ranging from 40.6 min (21.0) for
      an appointment in the index child only to 50 min (14.3) for an appointment in the
      index child and 2 other family members]. CONCLUSIONS: Contrary to healthcare
      provider perceptions, the timing of outpatient childhood vaccine appointments
      allows for the inclusion of pain management interventions. Efforts should now
      focus on educating healthcare providers and parents about the value of pain
      management and how to implement evidence-based strategies.

PMID- 21904198
TI  - Persistent pain after surgery for cutaneous melanoma.
AB  - OBJECTIVES: Chronic pain is a well-known complication after surgery, but the
      prevalence of persistent pain after melanoma surgery is unknown. This study
      examined the prevalence and predictors of persistent pain after melanoma surgery.
      METHODS: Between September 2005 and June 2009, 448 patients underwent surgery for
      cutaneous melanoma at the Department of Plastic Surgery, Aalborg Hospital. A
      questionnaire was sent to all 402 survivors, and 350 (87.1%) responded. In
      addition, all patients with pain and a control group of sex-matched and age
      matched patients without pain were invited to a clinical examination. RESULTS:
      Thirty-four patients (9.7%) reported pain in the scar area within the last month,
      and 8.6% reported chronic pain. The pain was mostly mild with little impact on
      daily life, but 1.7% reported moderate to severe pain, and 3.4% reported at least
      moderate impact of pain on daily life. Sensory changes were reported by 108
      patients (31.5%); 25% of these had pain compared with 3% of patients with normal
      sensation [P<0.001, 10.8 (4.5 to 25.8)]. Young age was a predictor for persistent
      pain. A small group of patients (10 with and 22 without pain in the
      questionnaire) were clinically examined, suggesting that the areas of sensory
      disturbances were larger in patients reporting persistent pain or dysesthesia.
      DISCUSSION: The results support previous findings that persistent postoperative
      pain is a complication of almost any surgical intervention. Persistent pain was
      related to abnormal sensation, and neuropathic pain should be considered in these
      patients.

PMID- 21904199
TI  - Bisphosphonates for pain management in children with benign cartilage tumors.
AB  - OBJECTIVES: Cochrane meta-analyses have shown significant benefit in bone pain
      from bisphosphonate therapy in adults with bone diseases such as multiple
      myeloma, Paget disease, breast and prostate cancer. Our aim was to assess if
      bisphosphonate treatment could alleviate severe pain in children with Ollier
      disease and hereditary multiple exostoses that are refractory to standard
      analgesics. METHODS: We report our clinical experience with bisphosphonate
      therapy in 2 children with cartilage tumors, one with Ollier disease, and the
      other with hereditary multiple exostoses. RESULTS: We found bisphosphonate
      therapy to be helpful for pain relief and improving overall ability to carry out
      daily activities. DISCUSSION: One can consider bisphosphonate therapy in children
      with Ollier disease and hereditary multiple exostoses who have debilitating pain
      that is refractory to standard analgesic treatment.

PMID- 21904200
TI  - A comparative investigation of observational pain assessment tools for older
      adults with dementia.
AB  - OBJECTIVES: Pain assessment in patients with dementia and severe limitations in
      ability to communicate can be challenging. The American Geriatrics Society (AGS)
      encourages the incorporation of 6 behavioral domains (ie, facial expressions,
      verbalizations/vocalizations, body movements, changes in interpersonal
      interactions, changes in activity patterns/routines and mental status changes)
      when conducting pain assessments among seniors with dementia. We investigated 6
      observational pain assessment measures (differing with respect to the extent that
      they cover the AGS-recommended domains) under 2 different pain conditions (ie,
      influenza vaccination and movement-exacerbated pain) in a sample of long-term
      care residents with cognitive impairments. Given that a criticism of pain
      assessment scales is that many of the pain behaviors assessed are highly
      overlapping with symptoms of delirium, we also investigated the impact of the
      elimination of delirium-related items. RESULTS: Consistent with expectations, all
      measures were able to differentiate between pain and baseline conditions.
      Reliability and validity varied across measures. Most measures continued to
      differentiate between pain and baseline states after items that overlap with
      delirium were eliminated. DISCUSSION: Our results provide much needed
      psychometric information regarding newly developed pain assessments measures for
      seniors with dementia. The measures differed with respect to ability to
      differentiate pain-related from non-pain-related states. Moreover, our findings
      support the utility of comprehensive coverage of the AGS-recommended pain
      assessment domains.

PMID- 21904201
TI  - Effectiveness of pain management in hospital in the home programs.
AB  - OBJECTIVES: The objective of the study was to examine patients' experiences of
      pain in Hospital in the Home (HITH) programs and identify the issues related to
      providing optimal pain management for acute care patients in the home
      environment. METHODS: A descriptive survey of patients' experience of pain and
      pain management in 3 HITH programs in metropolitan Melbourne, Australia (n=359).
      Data were collected by telephone interview using a modified version of The
      American Pain Society's Patient Outcome Questionnaire. Patients were interviewed
      48 to 72 hours after admission to the HITH program. Consecutive, adult, acute
      care patients were invited to participate in the study. Patients who had
      previously participated or had communication difficulties unable to be overcome
      with the assistance of an interpreter were excluded. RESULTS: Sixty-nine percent
      of patients interviewed experienced pain at home and 86% of these patients had
      experienced pain in the 24 hours before the interview. Over half (56%) of the
      patients had experienced moderate-to-severe worst pain in the previous 24 hours
      and 33% reported moderate-to-severe pain as their average pain experience. Two
      hundred thirty-two (93.2%) of the 250 patients who experienced pain had pain in
      hospital before being transferred to HITH. Of these patients, 52.2% (n=132) were
      prescribed analgesics to take home with them; the remaining 118 patients
      experiencing pain were not prescribed analgesics and either sourced analgesics
      once home (n=81, 68.1%) or did not take any analgesics (n=38, 31.9%). DISCUSSION:
      Treatment of pain at home was suboptimal with patients experiencing moderate-to
      severe pain and discomfort during the treatment phase of their illness. Lack of
      appropriate discharge planning strategies meant that patients went home without
      adequate analgesia and use of nonprescribed pain medication was common. The
      number of patients transferred home without analgesics indicates a worrying
      underrecognition of the need for analgesia in this care context and poses a risk
      to patient safety that is no less significant because patients are at home.

PMID- 21904202
TI  - Self-assessment of cognition in Multiple Sclerosis: the role of personality and
      anxiety.
AB  - OBJECTIVE: : To investigate the role of personality and anxiety to self-report
      measures of cognition in patients with multiple sclerosis (MS). BACKGROUND: :
      Self-report measures of cognition have consistently been shown to correlate
      better with depressed mood than neuropsychological test performance in patients
      with MS, with few studies focusing on the role of anxiety and personality.
      METHOD: : One hundred eight MS patients completed the following: (a) patient and
      informant report Multiple Sclerosis Neuropsychological Questionnaire (MSNQ); (b)
      Hospital Anxiety and Depression Scale; (c) cognitive assessment with the Brief
      Repeatable Battery of Neuropsychological Tests; and (d) personality assessment
      using the self-report NEO Five-Factor Inventory. RESULTS: : Higher patient MSNQ
      (P-MSNQ) scores (greater reported cognitive dysfunction) were significantly
      correlated with lower scores on the Paced Auditory Serial Addition Test (PASAT;
      r=-0.20, P<0.05), increased depression (r=0.45, P<0.01) and anxiety (r=0.54,
      P<0.01), higher neuroticism (r=0.51, P<0.01), and lower conscientiousness (r=
      0.35, P<0.01). After controlling for demographic variables, significant
      predictors of P-MSNQ scores were anxiety (DeltaR=0.272, P<0.001),
      conscientiousness (DeltaR=0.067, P=0.002), and performance on the PASAT
      (DeltaR=0.050, P=0.005). Depression and neuroticism did not contribute
      significant variance in comparison to anxiety. CONCLUSIONS: : Overall, patient
      self-reports of cognition did not correspond well to neuropsychological
      performance. Anxiety and conscientiousness contributed significantly to patients'
      perceptions of their cognitive failings and thus should be taken into account
      when addressing these complaints.

PMID- 21904203
TI  - Auditory outcomes after implantation and electrical stimulation of the lateral
      ampullar nerve in guinea pig.
AB  - OBJECTIVE: To determine in a guinea pig model the factors of invasiveness of a
      bipolar electrode implanted in the horizontal semicircular canal (HSC) and to
      evaluate the consequences on hearing of electrical stimulation of the ampullary
      nerve. DESIGN: Sixteen guinea pigs divided into four groups underwent surgical
      opening of the HSC of one ear as follows: control (group 1), cyanoacrylate glue
      application on the HSC opening (group 2), electrode implantation with
      cyanoacrylate glue on the HSC opening (group 3), and electrode implantation with
      electrical stimulation (1 hr/day) for 9 days (group 4). Auditory brainstem
      responses were recorded before and after surgery and after electrical
      stimulation. The effectiveness of electrical stimulation in producing a
      horizontal vestibulo-ocular reflex was evaluated by recording eye movement with
      video-oculography. RESULTS: Group 1 animals showed hearing loss, and in group 2,
      sealing the HSC opening with cyanoacrylate glue preserved the hearing thresholds.
      After electrode implantation, seven of the eight animals showed hearing loss
      compared with preoperative values. Electrical stimulation did not induce
      additional hearing loss. CONCLUSION: Electrode implantation at the canal level
      entailed a risk of hearing loss in an animal model, but electrical stimulation of
      the horizontal ampullary nerve did not further alter hearing function.

PMID- 21904204
TI  - Efficacy and safety of peginterferon alpha-2a (40 KD) plus ribavirin in treatment
      naive chronic hepatitis C patients in Central and Eastern Europe.
AB  - OBJECTIVE: Assess the safety and efficacy of 24 or 48 weeks of treatment with
      peginterferon alpha-2a (40 KD) plus ribavirin in treatment-naive patients with
      chronic hepatitis C. METHODS: All patients in this open-label multinational study
      were assigned at the investigator's discretion to receive peginterferon alpha-2a
      (40 KD) 180 ug/week plus ribavirin (800 mg/day) for a total of 24 weeks or
      peginterferon alpha-2a (40 KD) 180 ug/week plus ribavirin (1000/1200 mg/day) for
      a total of 48 weeks. Treatment success was defined as sustained virological
      response [sustained virological response (SVR); hepatitis C virus RNA less than
      50 IU/ml after completion of untreated follow-up]. RESULTS: A total of 789
      treatment-naive patients were enrolled, of whom 91% (138 of 152) of nongenotype 1
      patients and 77% (490 of 637) of genotype 1 patients completed 24 and 48 weeks of
      treatment, respectively. The overall SVR rate was 58% (459 of 789), and was 70
      and 55% in nongenotype 1 and genotype 1 patients, respectively. Age (per 10-year
      decrement) and baseline hepatitis C virus RNA level (<= 400 000 vs. >4 00 000
      IU/ml) were significantly associated with SVR by multiple logistic regression
      analysis. The safety profile of peginterferon alpha-2a (40 KD) plus ribavirin was
      similar to that reported in pivotal trials, with no new or unexpected safety
      signals. CONCLUSION: The combination of peginterferon alpha-2a (40 KD) plus
      ribavirin was well tolerated and produced an overall SVR rate of 58% in treatment
      naive patients. This study confirms that SVR rates achieved in pivotal clinical
      trials in Western Europe and the USA can be achieved in routine clinical practice
      in Central and Eastern Europe.

PMID- 21904205
TI  - The characteristics of the positivity to the lactulose breath test in patients
      with abdominal bloating.
AB  - OBJECTIVES: The clinical utility in patients with bloating is still conflicting.
      We aimed to evaluate the positivity to lactulose breath test (LBT) in patients
      with bloating, and to assess the clinical characteristics according to the
      positivity or subtypes of LBT. METHODS: The patients with abdominal bloating
      undergoing LBT were investigated. Rome III positive irritable bowel syndrome
      (IBS) and bowel symptoms were surveyed according to the positivity or subtypes of
      LBT. RESULTS: The prevalence of IBS and the positivity to LBT was 23.8% (86 of
      358) and 29.6% (106 of 358), respectively. The positivity to LBT and the
      prevalence in subtypes of LBT were not different according to the presence of
      IBS. The subtypes of LBT positive (+) patients were LBT (H2) with 61 (57.5%),
      (CH4)+ with 30 (28.3%), and (both) positive with 15 (14.2%). The LBT (H2)+ group
      was younger, and had higher symptomatic score for the bloating than that in the
      LBT negative (-) group. The LBT (CH4)+ group was older, and had higher scores of
      hard stool and strain than those of the LBT (-) group. In the fasting LBT (H2)+
      group (n=37) diagnosed by increased baseline H2, the scores for abdominal
      discomfort, bloating, and flatus were higher than those for the LBT (H2)+ or LBT(
      ) groups. CONCLUSIONS: The subtypes of the positivity to LBT according to the gas
      produced or the fasting H2 may contribute to specificity or severity of abdominal
      symptoms regardless of the presence of IBS.

PMID- 21904206
TI  - Upper gastrointestinal bleedings in patients with hereditary coagulation
      disorders in Northwest of Iran:  prevalence of Helicobacter pylori infection.
AB  - OBJECTIVE: Upper gastrointestinal (UGI) bleeding is one of the most life
      threatening complications, in up to 25% of persons with hemophilia (PWH).
      Recurrent bleeding is common and can be caused by the Helicobacter pylori
      infection. Our aim was to evaluate the role of H. pylori infection in UGI
      bleeding in PWH. MATERIAL AND METHODS: Ninety patients with hereditary bleeding
      disorders, 30 patients with (group A), and 60 patients without (group B) a
      history of UGI bleeding episodes were included. The prevalence of H. pylori
      infection was investigated by stool antigen test, and serum serologic tests
      including immunoglobulin G and anti-CagA. RESULTS: Among 90 patients (81 men,
      nine women, mean age 31.30 +/- 10.72 years), 66 patients with hemophilia A, 10
      patients with hemophilia B, six patients with Von Willebrand disease, five
      patients with platelet function disorders, and three patients with other factor
      deficiencies were evaluated. About 46.7% of patients in group A, and 23.3% of
      patients in group B were anti-CagA-positive (P=0.02), whereas 76.7% of patients
      in group A and 51.7% of patients in group B had H. pylori immunoglobulin G
      antibodies (P=0.02). H. pylori antigen in stool was positive in 76.7% in group A
      and 55% in group B (P=0.03). No statistically significant difference was found
      between type and severity of diseases and risk of UGI. CONCLUSION: H. pylori
      infection should be considered as an important cause of UGI bleeding in PWH. We
      would recommend stool antigen test as a new and noninvasive screening test for
      diagnosis of H. pylori infection in all patients with hereditary hemorrhagic
      disorders.

PMID- 21904207
TI  - Body mass index and the risk and prognosis of acute pancreatitis:  a meta
      analysis.
AB  - OBJECTIVE: BMI has been indicated to be associated with prognosis of acute
      pancreatitis (AP). However, the relationship between BMI and the risk of AP
      development is still unresolved. We examined this association by conducting a
      detailed meta-analysis. We also assessed its prognostic role by including more
      researches. METHODS: Studies were identified by searching MEDLINE and EMBASE
      through March 31, 2011. There were two end points in this meta-analysis: the risk
      of AP development and the outcome of AP (including severity, local complications,
      systemic complications, and mortality). Summary relative risks (SRRs) with their
      corresponding 95% confidence intervals (CIs) were calculated using a random
      effects model. RESULTS: Compared with normal weight individuals, obese
      individuals (BMI>30 kg/m2) had an increased risk of AP development (SRRs 1.34,
      95% CI: 1.07-1.68), with significant heterogeneity among these studies (P=0.002,
      I2=77.2%). In addition, compared with nonobese patients, obese patients developed
      significantly more severe AP (SRRs 1.82, 95% CI: 1.44-2.30), systemic
      complications (SRRs 1.71, 95% CI: 1.17-2.50), local complications (SRRs 2.32,
      95%CI: 1.79-3.00), and mortality (SRRs 2.21, 95% CI: 1.28-3.83). There was no
      heterogeneity among these studies. CONCLUSION: Findings from this meta-analysis
      indicated that obesity is not only associated with an increased risk of AP
      development, but it is also a poor prognostic factor for AP.

PMID- 21904208
TI  - Steatosis degree, measured by morphometry, is linked to other liver lesions and
      metabolic syndrome components in patients with NAFLD.
AB  - BACKGROUND AND AIM: We carried out morphometric measurements of steatosis to
      evaluate relationships between steatosis degree and other liver lesions or
      metabolic syndrome components in nonalcoholic fatty liver disease (NAFLD).
      PATIENTS AND METHODS: We developed an algorithm to measure steatosis area. Two
      hundred and fourteen patients with NAFLD were included in derivation (10) and
      validation (204) groups. Controls consisted of patients who were steatosis-free
      (12), patients with chronic hepatitis C (188), and patients with alcoholic
      chronic liver disease (94). RESULTS: Accuracy of steatosis area was considered as
      good or very good in at least 72% of cases by three pathologists. Steatosis areas
      were as follows: NAFLD = 10.3 +/- 9.7%, virus = 2.4 +/- 3.1%, alcohol = 7.8 +/-
      8.2% (P<0.0001). Steatosis area was closely related to steatosis grades in NAFLD
      (P<0.0001 for linear trend). Steatosis area increased from the fibrosis stage F0
      to the fibrosis state F2, then decreased in the stages F3 and F4 (cirrhosis)
      (P<0.0001 for quadratic trend). Fibrosis was present in an average steatosis area
      of approximately 4% (defining significant steatosis) and in nonalcoholic
      steatohepatitis by approximately 8% (defining severe steatosis). Steatosis and
      fibrosis area increased symmetrically until approximately 10%, then steatosis
      area decreased to null as average fibrosis area reached 32%. Average fasting
      glycemia (approximately 92 mg/dl) or triglycerides and BMI plateaued before a
      steatosis area of approximately 4%, then increased thereafter. Significant
      steatosis was present in 61.3% of NAFLD versus 20.2% of viral hepatitis
      (P<0.0001) and in 58.7% of alcoholic liver diseases (P=0.674). CONCLUSIONS: The
      average threshold of steatosis area is 4% for the development of fibrosis or
      metabolic syndrome components and 8% for nonalcoholic steatohepatitis. Steatosis
      area may contribute to defining the normal range and clinical course of metabolic
      components.

PMID- 21904209
TI  - The effect of temperature on soft contact lens modulus and diameter.
AB  - PURPOSE: To examine the relative changes in diameter and modulus of soft contact
      lenses when the temperature is raised from room temperature (RT) to eye
      temperature (ET). METHODS: Thirteen lens types including 9 silicone hydrogel
      lenses were measured for diameter and elastic modulus at RT (20 +/- 1 degrees C)
      and ET (34 +/- 1 degrees C). Lens diameter measurements were undertaken after
      equilibration in ISO saline in a temperature-controlled lens analyzer (Optimec,
      Ltd, Malvern, United Kingdom). Measurements of flexural modulus of elasticity
      were made using an Instron 3343 tensiometer (Instron, Norwood, MA) with the
      samples suspended in a temperature-controlled saline bath. RESULTS: All lens
      types reduced in diameter when raised to ET. The largest mean changes with
      silicone hydrogel and conventional hydrogel lenses were with Biofinity (Delta0.35
      mm) and Acuvue 2 (Delta0.28 mm), respectively. All the silicone hydrogels showed
      a statistically significant reduction in modulus when raised to ET ranging from
      Delta0.06 MPa with comfilcon A to Delta0.78 MPa with balafilcon A. All the
      conventional hydrogels showed relatively small changes (<0.05 MPa) in modulus.
      Two of the four conventional hydrogels showed a statistically significant change
      in modulus (etafilcon A and ocufilcon A), but these were small and believed to be
      clinically insignificant. CONCLUSIONS: This study has highlighted some clinically
      relevant changes in soft contact lens modulus and diameter when raised from RT to
      ET. It has also shown the importance of standardizing modulus measurement
      technique.

PMID- 21904210
TI  - Parents seek early intervention services for a two-year-old without autism.
AB  - Sam is a 27-month-old boy who you have followed since birth. He lives with his
      parents in a small resort town approximately 90 miles outside a major city. Both
      his parents are professionals in their late 30s and have been highly involved in
      his care since birth. At the 12-month visit, they were concerned about his
      difficulty regulating. He was not sleeping through the night and had significant
      difficulty with baths. His physical examination and growth were normal. His eye
      contact was good, although it was difficult to see him smile. He had 1 or 2 words
      and was beginning to walk independently.At the 15-month checkup, they continued
      to be concerned about his poor regulation. He napped sporadically, and he was
      very difficult to take out on errands as he did not like his car seat. He now had
      approximately 10 single words, was using his fingers to point, and very clearly
      waved "bye bye" as soon as you entered the room.At the 18-month checkup, they
      state that he has not yet learned the word "no." He will follow a 1-step command
      when he wants to but now has 15 single words without any combinations. He points
      for his needs and to show them something. He has become increasingly "shy" around
      strangers and prefers to play with one other child as opposed to a larger group.
      He does not like loud noises and prefers to go barefoot constantly. His physical
      examination was again normal as was his growth. He is referred for a full hearing
      evaluation, which is also normal. The family was referred to early intervention,
      and he began receiving speech and language therapy and occupational therapy for
      his sensory challenges as well as a play group.At the 24-month checkup, his
      language continued to consist of single words-now approximately 30. When the
      parents do not understand what he wants, he will often tantrum and has started
      banging his head on the floor when frustrated. He has no repetitive behaviors and
      is starting to demonstrate imaginative play. Bath time has becoming increasingly
      challenging because he does not like the sensation of soap and the water
      temperature must be "just right." You refer the child to a Developmental and
      Behavioral Pediatrician for evaluation and at 28 months he is seen. During his
      testing visit, he had decreased eye contact and followed his own agenda but
      improved significantly as testing progressed. As he got more comfortable, he
      began making good eye contact, social referenced, and exhibited joint attention
      with his parents and the examiner. He did not meet criteria for an autism
      spectrum disorder or specifically pervasive developmental disorder-not otherwise
      specified (PDD-NOS). He was given a diagnosis of mixed receptive and expressive
      language delay and disruptive behavior disorder with sensory processing
      problems.The parents come to you a month after their evaluation visit asking you
      to give him a "listed diagnosis of PDD-NOS" that could be removed when he turns 3
      years so that he may qualify for increased hours of services-up to 15 hours per
      week-as well as applied behavioral analysis therapy. A behavioral therapist
      through early intervention has told the family that he would benefit from this
      increased intervention, specifically applied behavioral analysis but the only way
      he can receive it is with a "medical diagnosis" on the autism spectrum. What do
      you do next?

PMID- 21904211
TI  - Attention deficit hyperactivity disorder and dirty electricity.

PMID- 21904212
TI  - The association between parent worry and young children's social-emotional
      functioning.
AB  - OBJECTIVE: : Behavioral health problems are reported to affect as many as 24% of
      children younger than 4 years. Screening within primary care settings remains
      low. Brief, inexpensive methods to identify children are needed. The objective of
      this study was to determine the extent to which parent worry about their
      children's behavior and development is associated with social-emotional problems.
      METHODS: : In this cross-sectional study, 378 Spanish and English speaking
      mothers of 12- to 48-month-old, underserved children were surveyed before a well
      child visit with the Brief Infant-Toddler Social-Emotional Assessment. This is a
      parent-report measure that was scored to identify clinically significant (CS)
      social-emotional problems (>=85th percentile) and at-risk (AR) problems (75th
      84th percentile). Parents rated their worry about their children's behavior and
      social-emotional development on 3 questions. RESULTS: : A total of 42.1% of
      children had AR or CS problems or low social competence, with 19.8% of these
      children having CS problems. Overall, 30.4% of parents expressed worry about
      social-emotional/behavioral issues. A total of 19.9% of parents expressed worry
      despite having rated their child's behavior in the normal range on the Brief
      Infant-Toddler Social-Emotional Assessment. Worry was significantly associated
      with having either AR or CS problems. However, worry significantly distinguished
      the CS group, but not the AR group, from the normal group. Parent worry regarding
      behavior and social-emotional development approached adequate sensitivity (66.7%)
      to identify children CS problems with specificity being 78.6%. Parent worry,
      however, was not adequately sensitive in detecting AR problems. Ethnic
      differences indicated that the sensitivity and specificity of worry to detect CS
      behavior and social-emotional problems were excellent in Hispanic families, but
      sensitivity was poor in African-American ones. Among parents with low educational
      attainment, sensitivity to detect CS behavior and social-emotional problems was
      excellent. CONCLUSIONS: : Parent worry regarding social-emotional/behavioral
      issues may be a useful adjunct to developmental surveillance, as it identifies
      children with the most significant behavioral and social-emotional problems.
      However, as a screening method to identify all young children with social
      emotional problems, parent worry does not currently achieve acceptable
      classification.

PMID- 21904215
TI  - Interferon-conditioned dendritic cells for melanoma immunotherapy.

PMID- 21904213
TI  - Social support for diabetes illness management: supporting adolescents and
      caregivers.
AB  - OBJECTIVE: The aim of this research study was to examine the relationship between
      4 sources of social support (support for the adolescent from family, support for
      the adolescent from friends, support for the caregiver from another adult, and
      support to the family from the health care provider) and adolescents' diabetes
      outcomes (illness management behavior and health status) using a diverse sample
      of urban adolescents. METHOD: One hundred forty-one adolescents with insulin
      managed diabetes and their primary caregivers completed questionnaires assessing
      social support and illness management behavior. Glucose meters were downloaded
      and hemoglobin A1c assays were obtained. Structural equation modeling was used to
      test a model social support informed by social ecological theory. RESULTS: The
      results of the structural equation modeling indicated that support for the
      caregiver from another adult was directly and positively related to support for
      the adolescent from family and indirectly related to better illness management.
      Support for the adolescent from family was directly related to better diabetes
      management and, through better management, to better diabetes health. Support to
      the family from the health care provider was not related to support for the
      adolescent and support to the adolescent from friends was not related to illness
      management, as hypothesized. CONCLUSION: This study identifies a novel target for
      social support intervention to improve adolescents' illness management behavior
      the caregivers of adolescents with diabetes. By enhancing the social support
      caregivers receive from other adults in their lives, caregivers' ability to
      support their adolescent children with diabetes might also be improved which, in
      turn, improves adolescents' illness outcomes.

PMID- 21904216
TI  - Redirected lysis of human melanoma cells by a MCSP/CD3-bispecific BiTE antibody
      that engages patient-derived T cells.
AB  - Melanoma-associated chondroitin sulfate proteoglycan (MCSP; also called HMW-MAA,
      CSPG4, NG2, MSK16, MCSPG, MEL-CSPG, or gp240) is a well characterized melanoma
      cell-surface antigen. In this study, a new bispecific T-cell engaging (BiTE)
      antibody that binds to MCSP and human CD3 (MCSP-BiTE) was tested for its
      cytotoxic activity against human melanoma cell lines. When unstimulated
      peripheral mononuclear blood cells (PBMCs) derived from healthy donors were
      cocultured with melanoma cells at effector:target ratios of 1:1, 1:5, or 1:10,
      and treated with MCSP-BiTE antibody at doses of 10, 100, or 1000 ng/mL, all MCSP
      expressing melanoma cell lines (n=23) were lysed in a dose-dependent and
      effector:target ratio-dependent manner, whereas there was no cytotoxic activity
      against MCSP-negative melanoma cell lines (n=2). To investigate whether T cells
      from melanoma patients could act as effector cells, we cocultured unstimulated
      PBMCs with allogeneic melanoma cells from 13 patients (4 stage I/II, 3 stage III,
      and 6 stage IV) or with autologous melanoma cells from 2 patients (stage IV).
      Although cytotoxic activity varied, all 15 PBMC samples mediated significant
      redirected lysis by the BiTE antibody. When PBMC or CD8 T cells were
      prestimulated by anti-CD3 antibody OKT-3 and interleukin-2, the MCSP-BiTE
      concentrations needed for melanoma cell lysis decreased up to 1000-fold. As MCSP
      is expressed on most human melanomas, immunotherapy with MCSP/CD3-bispecific
      antibodies merits clinical investigation.

PMID- 21904217
TI  - Functional consequences of human lymphocyte cryopreservation: implications for
      subsequent interactions of cells with endothelium.
AB  - In order to understand human inflammatory diseases and to develop and assess new
      therapeutic strategies targeting leukocyte recruitment to tissue, it is necessary
      to study human lymphocyte interactions with endothelium. It is often not
      practical to carry out assays on fresh human samples and therefore cells may be
      cryopreserved and batched for later study. Furthermore, many forms of adoptive
      cell therapy use cryopreserved cells that are required to migrate to tissue after
      infusion in vivo. The consequences of cryopreservation on the adhesion and
      migration of leukocytes is not known leading us to study the effects of
      cryopreservation on lymphocyte phenotype, migration, and adhesion.
      Cryopreservation and subsequent thawing did not alter the proportion of retrieved
      T cell subsets. Overall levels of expression of beta1 or beta2 integrins were
      unaffected but marked changes were observed in other relevant receptors.
      Expression of CD69, a transmembrane protein that plays a critical role in
      lymphocyte egress from tissues and the chemokine receptor CXCR4, increased on
      thawed populations and levels of CD62L and CXCR3 were reduced on thawed cells but
      restored if cells were allowed to recover after thawing. These changes were
      associated with modulation of the ability of lymphocytes to migrate across
      cytokine-stimulated monolayers of endothelium toward recombinant CXCL11 and
      CXCL12. Thus cryopreservation and thawing of lymphocytes induces changes in their
      adhesive phenotype and modulates their ability to migrate across endothelial
      monolayers. These findings have implications for in vitro experimentation and for
      cell therapy in which cryopreserved cells are expected to migrate when reinfused
      into patients.

PMID- 21904218
TI  - Adeno-associated virus-mediated local delivery of LIGHT suppresses tumorigenesis
      in a murine cervical cancer model.
AB  - LIGHT is a tumor necrosis factor superfamily ligand that is considered as a
      promising candidate for cancer therapy. It has a potent antitumor activity
      through establishing lymphoid-like tissues inside tumor sites and recruiting
      naive T cells into the tumor. In this study, we examined the possibility of
      antitumor activity by expressing LIGHT in cervical cancer (CC) model. A
      recombinant adeno-associated virus (AAV) vector was chosen for the transfer,
      based on its transfection efficiency and lack of detectable pathology. In vitro
      transfer of recombinant AAV vector expressing LIGHT (AAV-LIGHT) stimulated T
      lymphocyte proliferation and activation. AAV-mediated gene transfer of LIGHT by
      intratumoral injection exerted a very potent antitumor effect against preexisting
      TC-1 cell CC in C57BL/6 mice. This study confirmed that AAV-LIGHT regressed tumor
      growth by activating cytotoxic T lymphocyte, enhancing infiltration of
      inflammatory cells in tumor and increasing stimulatory cytokine expression in
      tumor microenvironment. Therefore, AAV-LIGHT therapy might have potential utility
      for the treatment of CC.

PMID- 21904219
TI  - Vaccines targeting the cancer-testis antigen SSX-2 elicit HLA-A2 epitope-specific
      cytolytic T cells.
AB  - The cancer-testis antigen synovial sarcoma X breakpoint-2 (SSX-2) is a
      potentially attractive target for tumor immunotherapy based upon its tissue
      restricted expression to germline cells and its frequent expression in
      malignancies. The goal of this study was to evaluate genetic vaccine encoding SSX
      2 to prioritize human leukocyte antigen (HLA)-A2-specific epitopes and determine
      if a DNA vaccine can elicit SSX-2-specific cytotoxic T lymphocytes (CTLs) capable
      of lysing prostate cancer cells. HLA-A2-restricted epitopes were identified based
      on their in vitro binding affinity for HLA-A2 and by the ability of a genetic
      vaccine to elicit peptide-specific CTL in A2/DR1 (HLA-A2.1+/HLA-DR1+/H-2 class I
      /class II-knockout) transgenic mice. We found that SSX-2 peptides p41-49
      (KASEKIFYV) and p103-111 (RLQGISPKI) had high affinity for HLA-A2 and were
      immunogenic in vivo; however, peptide p103-111 was immunodominant with robust
      peptide-specific immune responses elicited in mice vaccinated with a plasmid DNA
      vaccine encoding SSX-2. Furthermore, p103-111-specific CTLs were able to lyse an
      HLA-A2+ prostate cancer cell line. The immunodominance of this epitope was found
      not to be due to a putative HLA-DR1 epitope (p98-112) flanking p103-111. Finally,
      we demonstrated that SSX-2 epitope-specific CTLs could be detected and cultured
      from the peripheral blood of HLA-A2+ prostate cancer patients, notably patients
      with advanced prostate cancer. Overall, we conclude that SSX-2 peptide p103-111
      is an immunodominant HLA-A2-restricted epitope, and epitope-specific CD8 T cells
      can be detected in patients with prostate cancer, suggesting that tolerance to
      SSX-2 can be circumvented in vivo. Together, these findings suggest that SSX-2
      may be a relevant target antigen for prostate cancer vaccine approaches.

PMID- 21904220
TI  - Long-term intrathecal drug administration for chronic nonmalignant pain.
AB  - BACKGROUND: Chronic pain of nonmalignant origin requires effective long-term
      treatments, as for many patients pain management will be necessary throughout the
      rest of their lives. Intrathecal drug delivery systems (IDDS) have become a
      recognized therapy for the management of severe and otherwise intractable chronic
      pain. However, it is still not clear whether this treatment can be effective for
      periods up to 10 years or longer, given the paucity of long-term follow-up. This
      study sought to examine the effectiveness of IDDS following an average of 13
      years postimplantation. METHODS: Twenty patients participated in a longitudinal
      study with an average follow-up of 13.5 years (range: 10.4 to 17.9) after IDDS
      implantation. Investigation was carried out by means of a questionnaire before
      IDDS and after an average of 4 and 13 years of IDDS therapy. Assessment of
      pharmacological data and complications/side effects was performed. RESULTS:
      Statistically significant improvements between baseline and 4-year assessment
      were observed for the following sensory and psychosocial variables: pain
      intensity, pain relief, coping, self-efficacy, depression, quality of life,
      housework, mobility, sleep, and social life (all P<0.001). No statistically
      significant changes were detected between assessments at averages of 4 and 13.5
      years. CONCLUSIONS: This study, with one of the longest follow-up intervals
      reported in the IDDS literature, shows that IDDS has the potential to be a life
      long pain management solution in appropriately selected patients with chronic
      nonmalignant pain.

PMID- 21904221
TI  - Cerebral effect of acute normovolemic hemodilution during brain tumor resection.
AB  - BACKGROUND: Acute normovolemic hemodilution (ANH) is used in major surgery
      expected to be accompanied by excessive blood loss. Reducing the hemoglobin
      content may disturb cerebral oxygen balance. The aim of this study was to assess
      the effect of ANH on cerebral oxygen balance in patients subjected to brain tumor
      resection. METHODS: Forty patients were randomly allocated into 2 groups
      (hemodilution and control). In the hemodilution group (HG), 1000 mL of blood was
      drawn and replaced with the same volume of HES 130/0.4 (6%, Voluven) colloid. In
      the control group (CG), no blood was drawn, and hemodynamics were stabilized
      using normal saline until allogenic blood was needed. Arterial and jugular bulb
      blood samples obtained after induction (basal, sample 1), 40 minutes after
      induction (or on completion of hemodilution, sample 2), after surgical hemostasis
      (sample 3), and just before extubation (sample 4) were used for the calculation
      of arterial-jugular oxygen content difference "Ca-jO(2)," cerebral oxygen
      extraction "CEO(2)," estimated cerebral metabolic rate for oxygen "eCMRO(2),"
      cerebral blood flow equivalent "CBFe," and jugular-arterial lactate difference "J
      ALD" in both groups. RESULTS: Jugular oxygen saturation "SjvO(2)", CEO(2), and J
      ALD showed no significant difference when the 2 groups were compared at the
      corresponding time points and when the values obtained at different time points
      were compared with the basal value in the same group. In CG, "Ca-jO(2)"
      significantly decreased at the end of surgery and before tracheal extubation
      (P<0.003 and 0.002, respectively). In HG, it decreased after hemodilution, with P
      value of less than 0.032. eCMRO(2) was significantly reduced in CG 40 minutes
      after induction of anesthesia, at the end of surgery, and before tracheal
      extubation (P<0.021, 0.001, and 0.001, respectively). In HG, eCMRO(2) was
      significantly reduced at the end of hemodilution and at the end of surgery with P
      value of less than 0.005 and 0.034, respectively. CBFe was significantly
      increased in CG at the end of surgery and before tracheal extubation (P<0.005 and
      0.022, respectively). It was also increased after hemodilution in HG (P<0.042).
      There were no significant differences in Ca-jvO(2), eCMRO(2), and CBFe between
      the 2 groups. CONCLUSION: ANH and allogenic blood transfusion used in this study
      design were accompanied by comparable cerebral oxygenation parameters in patients
      subjected to brain tumor resection.

PMID- 21904222
TI  - Invited commentary. Emergency room coverage of orthopaedic injuries: a public
      relations problem.

PMID- 21904223
TI  - How do emergency department physicians rate their orthopaedic on-call coverage?
AB  - PURPOSE: Throughout the United States, the lack of orthopaedic on-call coverage
      at many institutions has been described as a "crisis." This study sought to
      understand how emergency department (ED) physicians perceive their orthopaedic on
      call coverage. Specifically, the study looked at availability of orthopaedic
      coverage, adequacy of coverage, and reasons for patient transfers. METHODS: After
      Institutional Review Board approval, written questionnaires were mailed to the ED
      directors at 39 of the 41 emergency departments in New Hampshire and Vermont. The
      instrument consisted of 25 items. Survey domains included ED physician
      demographics, availability and adequacy of orthopaedic coverage, and reasons for
      patient transfer. All responses were anonymous. RESULTS: A total of 31
      questionnaires was returned. Approximately one third (36%) of ED physicians
      reported they had full-time orthopaedic coverage with 8% reporting they "never"
      had coverage. Almost two thirds (64%) of respondents felt their daytime
      orthopaedic coverage was adequate, but this number dropped to 52% for night
      coverage and 48% for weekend coverage. Over half (55%) of respondents felt their
      orthopaedist was reluctant to come in to evaluate a patient when the ED physician
      felt the patient warranted orthopaedic consultation. Approximately half (52%)
      felt it was often the case that a patient's care could have been improved if they
      had been evaluated by an orthopaedist. Only 29% of respondents said their
      orthopaedist always came in when asked to evaluate a patient. The top three
      reasons ED physicians felt their orthopaedist declined to care for a patient were
      complexity of the injury, the time of day/night, and if it was a weekend.
      CONCLUSION/IMPLICATIONS: The findings in this study suggest there is substantial
      room for improvement in orthopaedic on-call coverage for emergency departments.

PMID- 21904225
TI  - Open clavicle fractures: patterns of trauma and associated injuries.
AB  - OBJECTIVES: To describe the demographic distribution, mechanism of injury, and
      associated injuries of patients sustaining open clavicle fractures. DESIGN:
      Retrospective case series. SETTING: Level I trauma center. PATIENTS/PARTICIPANTS:
      Trauma registry data from all patients who required admission to the hospital
      from October 1995 through January 2010, specifically patients with open clavicle
      fractures. INTERVENTION: Not applicable. MAIN OUTCOME MEASUREMENTS: The patterns
      of open clavicle fractures and their association with severe, nonorthopaedic
      injuries (head, thoracic, and great vessel). RESULTS: Fifty-three patients with
      open clavicle fractures were identified, and they were organized by mechanism of
      injury: 21 sustained blunt injuries, 26 penetrating injuries, and six not
      specified. No difference between blunt and penetrating injuries existed with
      respect to age, Injury Severity Score, inpatient days, or mortality rates. Blunt
      injuries were more likely associated with head injuries (52%) versus penetrating
      injuries (22%), but penetrating injuries were more likely associated with a great
      vessel injury (27% vs 7%, respectively), all statistically significant (P =
      0.0487). CONCLUSIONS: Open clavicle fractures are rare injuries. Patients often
      have associated head, thoracic, and great vessel injuries. Penetrating injuries
      have higher rates of great vessel injuries and that blunt force injuries have
      higher rates of head injuries.

PMID- 21904224
TI  - Influence of preoperative 7.5% hypertonic saline on neutrophil activation after
      reamed intramedullary nailing of femur shaft fractures: a prospective randomized
      pilot study.
AB  - OBJECTIVES: Femoral reaming and intramedullary nailing (IMN) primes
      polymorphonuclear leukocytes (PMNL) and thereby increases the posttraumatic
      systemic inflammatory response. Resuscitation with hypertonic saline (HTS)
      attenuates PMNL activation after trauma-hemorrhage. We hypothesized that
      preoperative administration of 7.5% HTS attenuates PMNL priming after IMN of
      unilateral femur shaft fractures compared with 0.9% normal saline. DESIGN:
      Prospective, randomized, double-blind study. SETTING: Level I trauma center.
      PATIENTS: Twenty patients between 18 and 80 years of age with an Injury Severity
      Score less than 25 and a unilateral femur shaft fracture amenable to IMN fixation
      within 24 hours after injury. INTERVENTION: Patients were allocated to equally
      sized HTS or normal saline treatment groups (n = 10) before surgery. Solutions
      were administered in a blinded bag as a single bolus of 4 mL/kg body weight
      immediately before surgery. Whole blood samples were collected directly before
      saline application (t0) and at 6, 12, and 24 hours after surgery. MAIN OUTCOME
      MEASUREMENTS: PMNL surface expression of CD11b and CD62L, as determined by flow
      cytometry analysis. RESULTS: Demographic characteristics of both treatment groups
      were comparable. Baseline expression of CD11b and CD62L cell markers was in a
      similar range in the two cohorts. The expression levels of CD11b were comparable
      between the two groups throughout the observation time, whereas CD62L levels were
      significantly higher in the HTS group at 6 and 24 hours after surgery. CONCLUSION
      AND SIGNIFICANCE: Preoperative infusion of HTS appears to exert an anti
      inflammatory effect by attenuating the extent of postoperative PMNL activation
      after reamed IMN for femoral shaft fractures.

PMID- 21904226
TI  - Analysis of past secular trends of hip fractures and predicted number in the
      future 2010-2050.
AB  - BACKGROUND: Understanding past trends and predicted future incidence of hip
      fractures is important for the assessment of Medicare sustainability and resource
      allocation. The purpose of this article was an analysis of most recent data on
      the incidence of hip fractures to predict the number of hip fractures that will
      occur in the United States from 2010 to 2050 in individuals 45 and older, by sex,
      and age distribution. METHOD: Prior hip fracture data were obtained from the
      National Hospital Discharge Survey during the period 1996-2006. These data were
      obtained from the US Department of Health and Human Services, Centers for Disease
      Control and Prevention, National Center for Health Statistics. Projected
      population estimates were obtained from the Population Division, US Census Bureau
      and Statistics, August 14, 2008. We used the past number and incidence of hip
      fractures extrapolated to population projections to predict the future number of
      hip fractures to 2050 using Application Software (SAS 9.2; SAS Institute Inc)
      regression model analysis. RESULTS: Two trends were identified from past reported
      rates of hip fractures. Trend 1 assumed a continued very slow decline in the
      incidence of hip fractures in the future yielding a conservative estimate of
      458,000 fractures by 2050. Trend 2 ignored the slight decrease in rate over past
      years and used a constant rate determined from linear regression providing an
      estimate as high as 1,037,000 in 2050. The largest number of fractures will occur
      in females older than 65 years. CONCLUSIONS: Future estimates of the number of
      hip fracture will likely fall between the 2 trends described within and by 2050
      may range from 458,000 to 1,037,000 with the largest number occurring in female
      older than 65 years.

PMID- 21904227
TI  - Femoral neck shortening and varus collapse after navigated fixation of
      intracapsular femoral neck fractures.
AB  - OBJECTIVE: Assessing femoral neck shortening (FNS) and varus collapse after
      internal fixation of femoral neck fractures using computerized navigation (CN).
      DESIGN: Retrospective cohort study. SETTINGS: Academic Level I trauma center.
      PATIENTS AND METHODS: Forty-one patients who had healed femoral neck fractures
      treated with CN between the years 2003 and 2008. Average age was 65 years (range,
      14-91 years). Thirty-six patients had nondisplaced fractures and five had
      displaced fractures. INTERVENTION: Screws were placed using CN in an inverted
      triangle formation Follow-up films were digitized into a PACS system, calibrated,
      and analyzed using CAD software. OUTCOME MEASURES: The following parameters were
      recorded: abductor lever arm shortening (termed x), corresponding vertical femur
      shortening (termed y), and the resultant femoral neck shortening vector (z).
      Fifteen patients were available for clinical outcome measures by the means of SF
      12 survey RESULTS: Significant FNS of the x component (greater than 5 mm)
      occurred in 30 of 42 (71%) patients with severe shortening (greater than 10 mm)
      in 25% of the patients. Significant y shortening occurred in 43% of the patients
      and severe shortening in 17%. Overall (z) femoral neck shortening occurred in 56%
      of the patients with severe shortening in 22% of patients. Varus collapse
      (greater than 5 degrees ) did not occur in any patient. Screw pullout (greater
      than 5 mm) occurred in 17 (41%) patients. Seven patients required late (greater
      than 6 months) arthroplasty postoperatively. FNS did not significantly correlate
      with fracture type, quality of reduction, age, or neck shaft angle. SF-12 results
      were negatively correlated with overall FNS. CONCLUSIONS: Our results show a high
      degree of FNS associated with the use of CN for fixation of femoral neck
      fractures, similar to recently published series using nonnavigated implants.
      However, no varus collapse occurred in our series. Our preliminary clinical data
      show a trend toward an adverse effect of FNS on quality-of-life measures.

PMID- 21904228
TI  - Augmented osteosynthesis of OTA 44-B fractures in older patients: a technique
      allowing early weightbearing.
AB  - OBJECTIVES: To determine the effectiveness of an augmented technique of
      osteosynthesis in allowing early weightbearing in older patients with OTA 44-B
      (Danis-Weber B) fractures. DESIGN: Case series. SETTING: University Level I
      trauma center. PATIENTS: Thirty-six patients, nonconsecutive, with OTA 44-B
      fractures. INTERVENTION: Augmented internal fixation using an intramedullary
      wire, lateral plate, and screw augmentation with polymethylmethacrylate. OUTCOME
      MEASURES:  MAIN OUTCOME: Healed fracture with no loss of reduction. SECONDARY
      OUTCOMES: American Orthopaedic Foot and Ankle Society score; percentage of
      patients who returned to prefracture function. RESULTS: All patients began
      weightbearing as tolerated in a removable brace at a mean of 13.5 days
      postoperatively. Thirty patients were available for follow-up at a minimum of 12
      months (range, 12-14 months). All fractures healed with no loss of reduction. The
      mean American Orthopaedic Foot and Ankle Society ankle-hindfoot score was 84.9
      (range, 74-100), and 90% of patients returned to prefracture function. There were
      two infections, one in a 74-year-old diabetic woman and the other in a 92-year
      old woman with pre-existing arterial insufficiency and a small ulcer over the tip
      of the second toe. CONCLUSIONS: Augmented internal fixation consisting of
      intramedullary wire, lateral plate, and screw augmentation with
      polymethylmethacrylate may allow for very early weightbearing without risk of
      secondary loss of reduction or disruption of the ankle mortise in older patients
      with OTA 44-B (Danis-Weber B) malleolar fractures.

PMID- 21904229
TI  - Superior versus anteroinferior plating of the clavicle: a finite element study.
AB  - OBJECTIVES: Fixation plate positioning remains controversial in clavicle fracture
      reconstruction. Biomechanical studies favor a superior plate placement and
      clinical series report very low mechanical complications for anteroinferior plate
      placement. To clarify this apparent discrepancy, a biomechanical finite element
      analysis of the deformation mode, stress patterns, and peak stresses involved
      with superior and anteroinferior clavicle plate fixation was performed. METHODS:
      Finite element models of the superior and anteroinferior reconstructions were
      built and the results were compared with those of the intact clavicle when loaded
      in axial compression and cantilever bending. RESULTS: Superior plate placement
      was less likely to fail in axial compression but the anteroinferior plate
      placement was less likely to fail in cantilever bending. For all placements and
      loading modes, the region near the fracture gap experienced the highest stresses
      and was consequently critical for the behavior of the whole construct. The
      anteroinferior placement led to a deformation mode similar to the intact clavicle
      in both loading configurations, whereas the deformation mode with the superior
      placement was non-physiological. CONCLUSIONS: Anterorinferior plating is
      generally preferable, because it induces deformation modes similar to the intact
      clavicle and is less likely to fail during normal physiological loading
      (cantilever bending). Superior placement of the reconstruction plate may be
      recommended for a patient with a high risk of shoulder impacts (axial
      compression). Design improvements in the bridging area of the plate and special
      attention to obtain a good fixation around the fracture could reduce plate
      failures and provide a stiffer construct.

PMID- 21904230
TI  - Randomized, prospective comparison of plate versus intramedullary nail fixation
      for distal tibia shaft fractures.
AB  - OBJECTIVES: Malalignment has been frequently reported after intramedullary
      stabilization of distal tibia fractures. Nails have also been associated with
      knee pain in several studies. Historically, plate fixation has resulted in
      increased risks of infection and nonunion. Our purposes were to compare plate and
      nail stabilization for distal tibia shaft fractures by assessing complications
      and secondary procedures. We hypothesized that nails would be associated with
      more malalignment and nonunion. DESIGN: Randomized, prospective study. SETTING:
      Level I trauma center. PATIENTS/PARTICIPANTS: One hundred four skeletally mature
      patients with extra-articular distal tibia shaft fractures with a mean age of 38
      years (range, 18-95 years) and mean Injury Severity Score of 13.5 (range, 9-50).
      The majority had high-energy injuries. INTERVENTION: Patients were randomized to
      a reamed intramedullary nail (n = 56) or a large fragment medial plate (n = 48).
      Forty fractures (39%) were open. Twenty-eight (27%) had concomitant fibula
      fractures that were stabilized. MAIN OUTCOME MEASUREMENTS: Malunion, nonunion,
      infection, and secondary operations. RESULTS: The two treatment groups were
      evenly matched with respect to age, gender, Injury Severity Score, fracture
      pattern, and presence of open fracture. Six patients (5.8%) developed deep
      infection with equal numbers in the two groups. Eighty-three percent of
      infections occurred after open fracture (P < 0.001). Four patients (7.1%)
      developed nonunion after nailing versus two (4.2%) after plating (P = 0.25) with
      a trend for nonunion in patients who had distal fibula fixation (12% versus 4.1%,
      P = 0.09). All nonunions occurred after open fracture (P = 0.0007); the primary
      union rate for closed fractures was 100%. Primary angular malalignment of 5
      degrees  or greater occurred in 13 patients with nails (23% of all nails) and
      four with plates (8.3% of all plates; P = 0.02 for plates versus nails). Six
      additional patients experienced malalignment after immediate weightbearing
      against medical advice. Valgus was the most common deformity (n = 16). Malunion
      was more common after open fracture (55%, P = 0.04). Eighty-five percent of
      patients with malalignment after nailing did not have fibula fixation. Eleven
      patients underwent 15 secondary procedures after plating, five of which were for
      prominent implant removal. This was not significantly different from patients
      treated with nailing: 10 patients had 14 procedures and five for prominent
      implant removal. CONCLUSIONS: High primary union rates were noted after surgical
      treatment of distal tibia shaft fractures with both nonlocked plates and reamed
      intramedullary nails. Rates of infection, nonunion, and secondary procedures were
      similar. Open fractures had higher rates of infection, nonunion, and malunion.
      Intramedullary nailing was associated with more malalignment versus plating.
      Fibula fixation may facilitate reduction of the tibia at the time of surgery. The
      effect of fibula fixation on tibia healing deserves further study. Economic
      assessment and functional outcomes data for this population will help to enhance
      our treatment decision-making.

PMID- 21904231
TI  - Impact of testing strategy on expression of upper-body work capacity and one
      repetition maximum prediction after resistance training in college-aged men and
      women.
AB  - The purpose of this study was to assess the effect of resistance training on
      upper-body muscular strength and the expression of work capacity and muscular
      endurance. In addition, a training-induced change in the relationship between
      muscular strength and endurance was assessed by testing changes in the accuracy
      of using endurance repetitions to predict 1 repetition maximum (1RM) bench press
      before and after training. College-aged men (n = 85) and women (n = 62) completed
      a 12-week linear periodization resistance training program. Before and after
      training, the subjects were assessed for 1RM and repetitions to fatigue (RTFs)
      with a submaximal load. After pretraining 1RM determination, the subjects were
      randomly assigned to perform RTFs at 65% 1RM (n = 74) or 90% 1RM (n = 73).
      Pretraining and posttraining RTFs were conducted at the same respective % 1RM.
      Work capacity was determined from repetition weight * RTF. After training, there
      was a significant increase in 1RM in both men (~14%) and women (~23%).
      Posttraining RTF was not different from pretraining RTF at 65 %1RM (18.2 +/- 5.1
      and 19.0 +/- 6.0, respectively) but was significantly reduced in the 90% 1RM
      group (6.1 +/- 3.6 vs. 4.5 +/- 2.7, respectively). Likewise, there was a
      differential effect of training on the expression of work capacity, which
      increased in the 65 % 1RM group (123 +/- 155 kg-reps) but decreased in the 90%
      1RM group (-62 +/- 208 kg-reps); the effect was independent of gender within each
      testing group. In conclusion, the changes in muscular strength associated with
      resistance training produced an increase in work capacity when tested with a 65 %
      1RM load without a change in endurance. In contrast, both work capacity and
      endurance decreased when tested with 90% 1RM. Thus, the impact of strength
      training on work capacity and muscle endurance is specific to the load at which
      endurance testing is performed.

PMID- 21904232
TI  - Effects of intensive physical rehabilitation on neuromuscular adaptations in
      adults with poststroke hemiparesis.
AB  - Hemiparesis-disability and muscle weakness of 1 side of the body-is a common
      consequence of stroke. High-intensity strength training may be beneficial to
      regain function, but strength coaches in the field of rehabilitation need
      evidence-based guidelines. The purpose of this study was to evaluate the effect
      of intensive physical rehabilitation on neuromuscular and functional adaptations
      in outpatients suffering from hemiparesis after stroke. A within-subject repeated
      measures design with the paretic leg as the experimental leg and the nonparetic
      leg as the control leg was used. Eleven outpatients with hemiparesis after stroke
      participated in 12 weeks of intensive physical rehabilitation comprising
      unilateral high-intensity strength training with near-maximal loads (4-12
      repetition maximum) and body weight supported treadmill training. At baseline and
      12-week follow-up, the patients went through testing consisting of isokinetic
      muscle strength, neuromuscular activation measured with electromyography (EMG),
      electrically evoked muscle twitch contractile properties, and gait performance
      (10-m Walk Test and 6-min Walk Test). After the 12-week conditioning program,
      knee extensor and flexor strength increased during all contraction modes and
      velocities in the paretic leg. Significant increases were observed for agonist
      EMG amplitude at slow concentric and slow eccentric contraction. Twitch torque
      increased, whereas twitch time-to-peak tension remained unchanged. By contrast,
      no significant changes were observed in the nonparetic control leg. Gait
      performance increased 52-68%. In conclusion, intensive physical rehabilitation
      after stroke leads to clinically relevant neuromuscular improvements, leading to
      increased voluntary strength during a wide range of contraction modes and
      velocities, and improved gait velocity. Strength training coaches working in the
      field of rehabilitation can use this knowledge to safely and efficiently add high
      intensity strength training to existing rehabilitation paradigms.

PMID- 21904233
TI  - High-intensity interval training vs. repeated-sprint training in tennis.
AB  - The aim of this study was to compare the effects of high-intensity interval
      training (HIIT) and repeated-sprint training (RST) on aerobic fitness, tennis
      specific endurance, linear and repeated-sprint ability (RSA), and jumping
      ability. Thirty-one competitive male tennis players took part in a training
      intervention of 6 weeks. The players were matched into 3 groups, HIIT (n = 11),
      RST (n = 12), or control group (CON, n = 9). The results showed significant time
      * intervention interactions for VO(2)peak, with a significant increase in the
      VO(2)peak level of 6.0% in HIIT (p = 0.008) and 4.9% in RST (p = 0.010), whereas
      no changes occurred in CON. However, the following differences were found between
      the intervention groups: The HIIT-induced greater improvements in tennis-specific
      endurance (HIIT 28.9% vs. RST 14.5%; p < 0.05) and RST led to a significant
      improvement in RSA (i.e., reduction in the mean sprint time of 3.8%; p < 0.05).
      Neither training strategy induced any effects on jumping and sprinting abilities.
      Both training interventions showed similar improvements in general aerobic
      fitness. Also, the present results suggest that RST represents a time-efficient
      stimulus for a simultaneous improvement of general and tennis-specific aerobic
      fitness as well for RSA.

PMID- 21904234
TI  - The convergent validity between two objective methods for quantifying training
      load in young taekwondo athletes.
AB  - Various studies used objective heart rate (HR)-based methods to assess training
      load (TL). The common methods were Banister's Training Impulse (TRIMP; weights
      the duration using a weighting factor) and Edwards' TL (a summated HR zone
      score). Both the methods use the direct physiological measure of HR as a
      fundamental part of the calculation. To eliminate the redundancy of using various
      methods to quantify the same construct (i.e., TL), we have to verify if these
      methods are strongly convergent and are interchangeable. Therefore, the aim of
      this study was to investigate the convergent validity between Banister's TRIMP
      and Edwards' TL used for the assessment of internal TL. The HRs were recorded and
      analyzed during 10 training weeks of the preseason period in 10 male Taekwondo
      (TKD) athletes. The TL was calculated using Banister's TRIMP and Edwards' TL.
      Pearson product moment correlation coefficient was used to evaluate the
      convergent validity between the 2 methods for assessing TL. Very large to nearly
      perfect relationships were found between individual Banister's TRIMP and Edwards'
      TL (r values from 0.80 to 0.99; p < 0.001). Pooled Banister's TRIMP and pooled
      Edwards' TL (pooled data n = 284) were nearly largely correlated (r = 0.89; p <
      0.05; 95% confidence interval: 0.86-0.91). In conclusion, these findings suggest
      that these 2 objective methods, measuring a similar construct, are
      interchangeable.

PMID- 21904235
TI  - The effect of acute stretching on agility performance.
AB  - Static stretching (SS) has shown decreases in many areas including strength,
      anaerobic power, and sprinting time. Dynamic stretching (DS) has shown increases
      in anaerobic power and decreases in sprinting time. Research on the effects of
      stretching on agility performance is limited. The purpose of this study was to
      determine the effect of SS and DS on performance time of a sport agility test.
      Sixty male subjects consisting of collegiate (n = 18) and recreational (n = 42)
      basketball athletes volunteered for the study. Subjects were randomly assigned to
      1 of 3 intervention groups: SS, DS, or no stretching (NS). All groups completed a
      10-minute warm-up jog followed by a 3-minute rest. The SS and DS groups then
      completed an 8.5-minute stretching intervention. Next, all subjects completed 3
      trials of the 505 agility test with 2-5 minutes of rest between trials. A 2-way
      repeated-measure analysis of variance (Stretch group, athlete category, group *
      athlete interaction) was used to determine statistical significance (p < 0.05). A
      Tukey post hoc test was performed to determine differences between groups. For
      all athletes, the DS group produced significantly faster times on the agility
      test (2.22 +/- 0.12 seconds, mean +/- SD) in comparison to both the SS group
      (2.33 +/- 0.15 seconds, p = 0.013) and NS group (2.32 +/- 0.12 seconds, p =
      0.026). Differences between the SS and NS groups revealed no significance (p =
      0.962). There was a significant difference in mean times for the type of athlete
      (p = 0.002); however, interaction between the type of athlete and stretching
      group was not significant (p = 0.520). These results indicate that in comparison
      to SS or NS, DS significantly improves performance on closed agility skills
      involving a 180 degrees  change of direction.

PMID- 21904237
TI  - Consistency of the counting talk test for exercise prescription.
AB  - The purpose of this study was to assess the consistency of the counting talk test
      (CTT) method for estimating exercise intensity across various modes of exercise
      in healthy young adults. Thirty-six individuals completed the study, which
      required participation in 3 separate sessions within a 2-week time period. During
      the first session, the individuals completed a maximal effort treadmill test from
      which each individual's heart rate reserve (HRR) was calculated. During the
      second and third sessions, the subjects participated in 2 modes of exercise in
      each session for a total of 4 different modes of exercise. The individuals
      exercised at 40% HRR, 50% HRR, 60% HRR, 75% HRR, and 85% HRR. The heart rate
      (HR), CTT, and rating of perceived exertion (RPE) were recorded at each workload.
      Based on the individual's resting CTT (CTT(rest)), the %CTT for each exercise
      stage was then calculated. Pearson correlations demonstrated moderate to good
      correlations between the CTT and HRR methods and the CTT and RPE methods for
      estimating exercise intensity. This study found that for the individuals with
      CTT(rest) <25, moderate to vigorous intensity exercise as recommended by the
      American College of Sports Medicine HRR guidelines could be achieved by
      exercising at a level of 40-50% CTT(rest). Individuals with a CTT(rest) >=25,
      exercising at a level of 30-40% CTT(rest) would place them in the moderate to
      vigorous exercise intensity range. A high degree of reliability was demonstrated
      using the CTT method across the various modes of aerobic exercise. As such,
      independent of the exercise mode, the CTT was found to be an easy and consistent
      method for prescribing moderate to vigorous aerobic exercise intensity.

PMID- 21904238
TI  - Vertical jumping tests in volleyball:  reliability, validity, and playing
      position specifics.
AB  - Vertical jumping is known to be important in volleyball, and jumping performance
      tests are frequently studied for their reliability and validity. However, most
      studies concerning jumping in volleyball have dealt with standard rather than
      sport-specific jumping procedures and tests. The aims of this study, therefore,
      were (a) to determine the reliability and factorial validity of 2 volleyball
      specific jumping tests, the block jump (BJ) test and the attack jump (AJ) test,
      relative to 2 frequently used and systematically validated jumping tests, the
      countermovement jump test and the squat jump test and (b) to establish volleyball
      position-specific differences in the jumping tests and simple anthropometric
      indices (body height [BH], body weight, and body mass index [BMI]). The BJ was
      performed from a defensive volleyball position, with the hands positioned in
      front of the chest. During an AJ, the players used a 2- to 3-step approach and
      performed a drop jump with an arm swing followed by a quick vertical jump. A
      total of 95 high-level volleyball players (all men) participated in this study.
      The reliability of the jumping tests ranged from 0.97 to 0.99 for Cronbach's
      alpha coefficients, from 0.93 to 0.97 for interitem correlation coefficients and
      from 2.1 to 2.8 for coefficients of variation. The highest reliability was found
      for the specific jumping tests. The factor analysis extracted one significant
      component, and all of the tests were highly intercorrelated. The analysis of
      variance with post hoc analysis showed significant differences between 5 playing
      positions in some of the jumping tests. In general, receivers had a greater
      jumping capacity, followed by libero players. The differences in jumping
      capacities should be emphasized vis-a-vis differences in the anthropometric
      measures of players, where middle hitters had higher BH and body weight, followed
      by opposite hitters and receivers, with no differences in the BMI between
      positions.

PMID- 21904239
TI  - Energy expenditure during tennis play: a preliminary video analysis and metabolic
      model approach.
AB  - The aim of this study was to estimate, using video analysis, what proportion of
      the total energy expenditure during a tennis match is accounted for by aerobic
      and anaerobic metabolism, respectively. The method proposed involved estimating
      the metabolic power (MP) of 5 activities, which are inherent to tennis: walking,
      running, hitting the ball, serving, and sitting down to rest. The energy
      expenditure concerned was calculated by sequencing the activity by video
      analysis. A bioenergetic model calculated the aerobic energy expenditure
      (EEO2mod) in terms of MP, and the anaerobic energy expenditure was calculated by
      subtracting this (MP - EEO2mod). Eight tennis players took part in the experiment
      as subjects (mean +/- SD: age 25.2 +/- 1.9 years, weight 79.3 +/- 10.8 kg, VO2max
      54.4 +/- 5.1 ml.kg(-1).min(-1)). The players started off by participating in 2
      games while wearing the K4b2, with their activity profile measured by the video
      analysis system, and then by playing a set without equipment but with video
      analysis. There was no significant difference between calculated and measured
      oxygen consumptions over the 16 games (p = 0.763), and these data were strongly
      related (r = 0.93, p < 0.0001). The EEO2mod was quite weak over all the games
      (49.4 +/- 4.8% VO2max), whereas the MP during points was up to 2 or 3 times the
      VO2max. Anaerobic metabolism reached 32% of the total energy expenditure across
      all the games 67% for points and 95% for hitting the ball. This method provided a
      good estimation of aerobic energy expenditure and made it possible to calculate
      the anaerobic energy expenditure. This could make it possible to estimate the
      metabolic intensity of training sessions and matches using video analysis.

PMID- 21904240
TI  - Test-retest reliability of the five-repetition sit-to-stand test: a systematic
      review of the literature involving adults.
AB  - The 5-repetition sit-to-stand test (FRSTST) is a widely used measure of
      functional strength, particularly among older adults. The purpose of this review
      was to summarize the findings of research using the intraclass correlation
      coefficient (ICC) to describe the test-retest reliability of the FRSTST. A search
      of 3 electronic databases and hand searches were used to identify relevant
      articles. Information on the subjects, test sessions and the ICCs reported was
      abstracted from the articles. The searches identified 10 relevant articles. The
      ICCs reported in the articles ranged from 0.64 to 0.96. The adjusted mean ICC
      calculated from the reported ICCs was 0.81. The test-retest reliability of the
      FRSTST can be interpreted as good to high in most populations and settings.

PMID- 21904241
TI  - Time course of the effects of static stretching on cycling economy.
AB  - Stretching has been implemented as part of the warm-up before physical events and
      widely thought to promote increased sport performance and decreased injury risk.
      However, recent research has concluded that static stretching before many
      exercises inhibits acute power, strength, and sprinting performance. There is
      little research examining the time course of these effects on moderate intensity
      cycling. The purpose of this study was to examine the time course of static
      stretching on cycling economy. The subjects consisted of 5 men and 5 women highly
      trained endurance cyclists. The first of 3 visits was baseline testing of their
      cycling VO2max. The second and third visits were either stretching or no
      stretching before a 30-minute stationary ride at 65% of their VO2max. The
      stretching condition consisted of four 30-second repetitions of 5 stretches with
      an average total stretching time of 16 minutes. VO2 demonstrated a significant
      condition by time interaction with the 5-minute time point being significantly
      less in the nonstretching condition (32.66 +/- 5.35 ml.kg(-1).min(-1)) than
      stretching (34.39 +/- 5.39 ml.kg(-1).min(-1)). No other time points were
      different. Our results demonstrate that static stretching yielded an acute
      increase in submaximal VO2; therefore, coaches and highly trained endurance
      cyclists should exclude static stretching immediately before moderate intensity
      cycling because it reduces acute cycling economy.

PMID- 21904242
TI  - Efficacy of potentiation of performance through overweight implement throws on
      male and female collegiate and elite weight throwers.
AB  - The purpose of this investigation was to determine the acute effects of 2
      different overweight implements on weight throw performance. Seventeen collegiate
      and elite weight throwers were recruited to participate. A within-subject design
      was used to compare the difference between mean and peak distance after warm-up
      with a regulation weight (STAND), 1.37-kg overweight (OVRWGHT1), and 2.27-kg
      overweight implement (OVRWGHT2). Repeated-measures analysis of variance revealed
      a main effect for Treatment (p = 0.006) and a significant interaction effect for
      Treatment by Time (p = 0.041). The means for the OVRWGHT1 treatment (16.08 +/-
      2.5 m) and OVRWGHT2 (16.08 +/- 2.7 m) were not different; however, the mean for
      STAND was significantly lower than that for the other treatments (15.58 +/- 2.5,
      p < 0.02). Changes in performance between OVRWGHT treatments and STAND were found
      to correlate to one-repetition maximum (1RM) Power Clean (improvement for OVRWGHT
      1, r = 0.536, p = 0.016; improvement for OVRWGHT2, r = 0.548, p = 0.014). The
      results suggest that in collegiate and elite athletes overweight implement warm
      up may improve performance and that stronger athletes may be better suited to
      take advantage of this effect.

PMID- 21904243
TI  - Fit-climbing test:  a field test for indoor rock climbing.
AB  - The aim of this study was to develop an indoor rock-climbing test on an
      artificial wall (Fit-climbing test). Thirteen climbers (elite group [EG] = 6;
      recreational group [RG] = 7) performed the following tests: (a) familiarization
      in the Fit-climbing test, (b) the Fit-climbing test, and (c) a retest to evaluate
      the Fit-climbing test's reliability. Gas exchange, blood lactate concentration,
      handgrip strength, and heart rate were measured during the test. Oxygen uptake
      during the Fit-climbing test was not different between groups (EG = 8.4 +/- 1.1
      L; RG = 7.9 +/- 1.5 L, p > 0.05). The EG performance (120 +/- 7 movements) was
      statistically higher than the RG climbers' performance (78 +/- 13 movements)
      during the Fit-climbing test. Consequently, the oxygen cost per movement during
      the Fit-climbing test of the EG was significantly lower than that of the RG (p <
      0.05). Handgrip strength was higher in the EG when compared with that in the RG
      in both pre-Fit- and post-Fit-climbing test (p < 0.05). There were no significant
      differences in any other variables analyzed during the Fit-climbing test (p >
      0.05). Furthermore, the performance in the Fit-climbing test presented high
      reliability (intraclass correlation coefficient = 0.97). Therefore, the
      performance during the Fit-climbing test may be an alternative to evaluate rock
      climbers because of its specificity and relation to oxygen cost per movement
      during climbing.

PMID- 21904244
TI  - The effects of 6 weeks of preseason skill-based conditioning on physical
      performance in male volleyball players.
AB  - The purpose of this study was to determine the changes in physical performance
      after a 6-week skill-based conditioning training program in male competitive
      volleyball players. Sixteen male volleyball players (mean +/- SD: age 22.3 +/-
      3.7 years, body height 190.7 +/- 4.2 cm, and body mass 78.4 +/- 4.5 kg)
      participated in this study. The players were tested for sprinting (5- and 10-m
      sprint), agility, and jumping performance (the vertical-jump test, the spike-jump
      test, and the standing broad jump [SBJ]). Compared with pretraining, there was a
      significant improvement in the 5- and 10-m speed. There were no significant
      differences between pretraining and posttraining for lower-body muscular power
      (vertical-jump height, spike-jump height, and SBJ) and agility. Based on our
      results, it could be concluded that a preseason skill-based conditioning program
      does not offer a sufficient stimulus for volleyball players. Therefore, a general
      conditioning and hypertrophy training along with specific volleyball conditioning
      is necessary in the preseason period for the development of the lower-body
      strength, agility and speed performance in volleyball players.

PMID- 21904245
TI  - Physical demands of National Collegiate Athletic Association Division I football
      players during preseason training in the heat.
AB  - The purpose of this study was to evaluate physical demands of football players
      during preseason practices in the heat. Furthermore, we sought to compare how
      physical demands differ between positions and playing status. Male National
      Collegiate Athletic Association Division 1 football players (n = 49) participated
      in 9 practice sessions (142 +/- 16 minutes per session; wet bulb globe
      temperature (WBGT) 28.75 +/- 2.11 degrees C) over 8 days. Heart rate (HR) and
      global positioning system data were recorded throughout the entirety of each
      practice to determine the distance covered (DC), velocity (V), maximal HR
      (HRmax), and average HR (HRavg). The subjects were divided into 2 groups: linemen
      (L) (N = 25; age: 22 +/- 1 years, weight: 126 +/- 16 kg, height: 190 +/- 4 cm,)
      vs. nonlinemen (NL) (N = 24; age: 21 +/- 1 years, weight: 91 +/- 11 kg, height:
      183 +/- 8 cm) and starters (S) (N = 17; age: 21 +/- 1 years, weight: 118 +/- 21
      kg, height: 190 +/- 7 cm) vs. nonstarters (NS) (N = 32; age: 20 +/- 1 years,
      weight: 105 +/- 22 kg, height: 185 +/- 7 cm) for statistical analysis. The DC
      (3,532 +/- 943 vs. 2,573 +/- 489 m; p = 0.001) and HRmax (201 +/- 9 vs. 194 +/-
      11 b.min(-1); p = 0.025) were significantly greater in NL compared with that in
      L. In addition, NL spent more time (p < 0.0001) and covered more distance (p =
      0.002) at higher velocities than L did. Differences between S vs. NS were
      observed (p = 0.008, p = 0.031), with S obtaining higher velocities than NS did.
      Given the demands of their playing positions, NL were required to cover more
      distance at higher velocities, resulting in a greater HRmax than that of L.
      Therefore, it appears that L engage in more isometric work than NL do. In
      addition, the players exposed to similar practice demands provide similar work
      output during preseason practice sessions regardless of their playing status.

PMID- 21904246
TI  - Mechanically braked elliptical Wingate test: modification considerations, load
      optimization, and reliability.
AB  - The 30-second, all-out Wingate test evaluates anaerobic performance using an
      upper or lower body cycle ergometer (cycle Wingate test). A recent study showed
      that using a modified electromagnetically braked elliptical trainer for Wingate
      testing (EWT) leads to greater power outcomes because of larger muscle group
      recruitment. The main purpose of this study was to modify an elliptical trainer
      using an easily understandable mechanical brake system instead of an
      electromagnetically braked modification. Our secondary aim was to determine a
      proper test load for the EWT to reveal the most efficient anaerobic test outcomes
      such as peak power (PP), average power (AP), minimum power (MP), power drop (PD),
      and fatigue index ratio (FI%) and to evaluate the retest reliability of the
      selected test load. Delta lactate responses (DeltaLa) were also analyzed to
      confirm all the anaerobic performance of the athletes. Thirty healthy and well
      trained male university athletes were selected to participate in the study. By
      analysis of variance, an 18% body mass workload yielded significantly greater
      test outcomes (PP = 19.5 +/- 2.4 W.kg, AP = 13.7 +/- 1.7 W.kg, PD = 27.9 +/- 5
      W.s, FI% = 58.4 +/- 3.3%, and DeltaLa = 15.4 +/- 1.7 mM) than the other (12-24%
      body mass) tested loads (p < 0.05). Test and retest results for relative PP, AP,
      MP, PD, FI%, and DeltaLa were highly correlated (r = 0.97, 0.98, 0.94, 0.91,
      0.81, and 0.95, respectively). In conclusion, it was found that the mechanically
      braked modification of an elliptical trainer successfully estimated anaerobic
      power and capacity. A workload of 18% body mass was optimal for measuring maximal
      and reliable anaerobic power outcomes. Anaerobic testing using an EWT may be more
      useful to athletes and coaches than traditional cycle ergometers because a
      greater proportion of muscle groups are worked during exercise on an elliptical
      trainer.

PMID- 21904247
TI  - Chocolate milk and endurance exercise recovery:  protein balance, glycogen, and
      performance.
AB  - PURPOSE: This study examined effects of fat-free chocolate milk (MILK)
      consumption on kinetic and cellular markers of protein turnover, muscle glycogen,
      and performance during recovery from endurance exercise. METHODS: Male runners
      participated in two trials separated by 1 wk and consumed either MILK or a
      nonnitrogenous isocaloric carbohydrate (CHO) control beverage (CON) after a 45
      min run at 65% of VO(2peak). Postexercise muscle protein fractional synthetic
      rate (FSR) and whole-body protein turnover were determined during 3 h of recovery
      using muscle biopsies and primed constant infusions of L-[ring-2H5]phenylalanine
      and L-[1-13C]leucine, respectively. Phosphorylation of translational signaling
      proteins and activity of proteolytic molecules were determined using Western
      blotting and enzymatic activity assays. Muscle glycogen was quantified, and
      treadmill time to exhaustion was determined after the recovery period. RESULTS:
      Consuming MILK after exercise resulted in higher mixed muscle FSR with lower
      whole-body proteolysis and synthesis compared with CON (P <= 0.05).
      Phosphorylation of eIF4E-BP1 and FOXO3a was higher for MILK (P < 0.01), whereas
      Akt phosphorylation was lower during recovery regardless of dietary treatment (P
      < 0.05). Enzymatic activity assays indicated lower caspase-3 activity during
      recovery for MILK (P < 0.01) and higher 26S proteasome activity for CON (P <
      0.01). Muscle glycogen was not affected by either dietary treatment; however,
      time to exhaustion was greater for MILK than for CON (P < 0.05). CONCLUSIONS: The
      effects of consumption of MILK after endurance exercise on FSR, signaling
      molecules of skeletal muscle protein turnover, leucine kinetics, and performance
      measures suggest unique benefits of milk compared with a CHO-only beverage.

PMID- 21904248
TI  - Adjustments in motor unit properties during fatiguing contractions after
      training.
AB  - OBJECTIVE: The objective of the study was to investigate the effect of strength
      and endurance training on muscle fiber membrane properties and discharge rates of
      low-threshold motor units of the vasti muscles during fatiguing contractions.
      METHODS: Twenty-five sedentary healthy men (age (mean +/- SD) = 26.3 +/- 3.9 yr)
      were randomly assigned to one of three groups: strength training, endurance
      training, or a control group. Conventional endurance and strength training was
      performed 3 d.wk-1, during a period of 6 wk. Motor unit conduction velocity and
      EMG amplitude of the vastus medialis obliquus and lateralis muscles and biceps
      femoris were measured during sustained isometric knee extensions at 10% and 30%
      of the maximum voluntary contraction before and immediately after training.
      RESULTS: After 6 wk of training, the reduction in motor unit conduction velocity
      during the sustained contractions at 30% of the maximum voluntary force occurred
      at slower rates compared with baseline (P < 0.05). However, the rate of decrease
      was lower after endurance training compared with strength training (P < 0.01).
      For all groups, motor unit discharge rates declined during the sustained
      contraction (P < 0.001), and their trend was not altered by training. In
      addition, the biceps femoris-vasti coactivation ratio declined after the
      endurance training. CONCLUSIONS: Short-term strength and endurance training
      induces alterations of the electrophysiological membrane properties of the muscle
      fiber. In particular, endurance training lowers the rate of decline of motor unit
      conduction velocity during sustained contractions more than strength training.

PMID- 21904249
TI  - Evaluation of activity monitors in controlled and free-living environments.
AB  - Numerous studies have established the usefulness of pedometers and accelerometers
      as objective activity monitors. Under laboratory conditions, some of these
      devices have been shown to provide accurate and reliable measures of steps.
      However, limited data exist on the performance of these devices under free-living
      conditions. PURPOSE: This study aimed 1) to compare the effects of speed and body
      mass index (BMI) on the step count accuracy of five different accelerometer-based
      activity monitors and a pedometer during treadmill walking, 2) to compare the
      performance of these devices in a free-living environment, and 3) to compare the
      step counts of three generations of a single device (ActiGraph) against a
      criterion method. METHODS: Fifty-six individuals wore six activity monitors while
      performing treadmill walking (40, 54, 67, 80, and 94 m.min-1) and during 1 d of
      free-living activity. The criterion measure of steps during treadmill walking was
      investigator-determined steps, whereas the criterion measure of steps during the
      free-living condition was the StepWatch. RESULTS: BMI had no effect on step count
      accuracy during treadmill walking. The StepWatch, activPALTM, and the AG7164 were
      the most accurate across all speeds, whereas the remaining devices were only
      accurate at 67 m.min-1 and faster. In the free-living environment, the AG7164
      recorded 99.5% +/- 27% (mean +/- SD) of StepWatch-determined steps. CONCLUSIONS:
      We demonstrated that BMI does not affect the step output of commonly used
      activity monitors during walking. In addition, 67 m.min-1 seems to be the minimum
      speed required for accurate step counting, at least for most waist-mounted
      activity monitors. Finally, the StepWatch, AG7164, and activPALTM were the most
      accurate devices on the TM, but only the AG7164 yielded comparable step counts to
      the StepWatch in the free-living environment.

PMID- 21904250
TI  - Selective influence of auditory distractors on motor cortex excitability.
AB  - The diversion of attention from a primary goal by irrelevant events is known as
      attention capture, and is often followed by a directed action. The hypothesis
      that corticospinal excitability is modulated by attention capture was tested
      using transcranial magnetic stimulation. Participants watched a video while
      sounds were intermittently presented. Motor evoked potentials (MEPs) were
      elicited in each hand using transcranial magnetic stimulation 1 s after sound
      onset. MEP amplitudes were assessed as a function of hand (dominant,
      nondominant), sound location (ipsilateral or contralateral to hand location), and
      sound sample valence (negative, neutral, positive). Results showed that MEP
      amplitudes increased during sound presentation, but only for the dominant hand.
      There were no effects of location or emotional valence. The selective modulation
      of the dominant hand motor cortex may indicate that auditory events can prime the
      preferred hand for action.

PMID- 21904251
TI  - Anatomical study on the "perforator-free zone": reconsidering the proximal
      superior cerebellar artery and basilar artery perforators.
AB  - BACKGROUND: The proximal superior cerebellar artery (pSCA) is often considered a
      perforator-free area. Precise anatomical knowledge of this region clarifies the
      pathophysiology underlying posterior fossa ischemic syndromes and helps avoid
      treatment-related complications. OBJECTIVE: To anatomically evaluate perforating
      branches arising from the pSCA and the upper basilar artery (BA). METHODS: Forty
      four SCAs from 20 cadaveric heads were examined to determine patterns of the
      pSCA; its morphometry for medial and lateral branches; and frequency, number,
      diameter, distribution, and vascular territory of perforators arising from the
      pSCA and rostral BA. RESULTS: SCA arose as a single trunk in 36 sides (90%): mean
      diameter at origin was 1.38 mm; mean length was 14.4 +/- 7.9 mm. Ninety-nine pSCA
      perforator branches were present in 82% of specimens (mean, 2.3 +/- 1.6; range, 0
      7 perforators/side). Of these, 59% were direct, belonging to the interpeduncular
      group in 85% of cases; 28% were short circumflex, belonging to lateral and medial
      pontine group; and 13% were long circumflex, reaching the medullary perforation
      zone (basal cerebellar group). Median distance to the first perforator was 2.0 mm
      (range, 0.1-15 mm). There were 132 perforator branches in the last centimeter of
      the BA. CONCLUSION: The pSCA should not be regarded as a perforator-free area.
      Although the pSCA territories likely overlap with the posterior cerebral artery,
      BA, and anterior inferior cerebellar artery, the pSCA segment cannot be
      surgically manipulated with impunity.

PMID- 21904253
TI  - Prognostic value of major extracranial injury in traumatic brain injury: an
      individual patient data meta-analysis in 39,274 patients.
AB  - BACKGROUND: Major extracranial injury (MEI) is common in traumatic brain injury
      (TBI) patients, but the effect on outcome is controversial. OBJECTIVE: To assess
      the prognostic value of MEI on mortality after TBI in an individual patient data
      meta-analysis of 3 observational TBI studies (International Mission on Prognosis
      and Clinical Trial Design in TBI [IMPACT]), a randomized controlled trial
      (Corticosteroid Randomization After Significant Head Injury [CRASH]), and a
      trauma registry (Trauma Audit and Research Network [TARN]). METHODS: MEI
      (extracranial injury with an Abbreviated Injury Scale >= 3 or requiring hospital
      admission) was related to mortality with logistic regression analysis, adjusted
      for age, Glasgow Coma Scale motor score, and pupil reactivity and stratified by
      TBI severity. We pooled odds ratios (ORs) with random-effects meta-analysis.
      RESULTS: We included 39,274 patients. Mortality was 25%, and 32% had MEI. MEI was
      a strong predictor for mortality in TARN, with adjusted odds ratios of 2.81 (95%
      confidence interval [CI], 2.44-3.23) in mild, 2.18 (95% CI, 1.80-2.65) in
      moderate, and 2.14 (95% CI, 1.95-2.35) in severe TBI patients. The prognostic
      effect was smaller in IMPACT and CRASH, with pooled adjusted odds ratios of 2.14
      (95% CI, 0.93-4.91) in mild, 1.46 (95% CI, 1.14-1.85) in moderate, and 1.18 (95%
      CI, 1.03-1.55) in severe TBI. When patients who died within 6 hours after injury
      were excluded from TARN, the effect of MEI was comparable with IMPACT and CRASH.
      CONCLUSION: MEI is an important prognostic factor for mortality in TBI patients.
      However, the effect varies by population, which explains the controversy in the
      literature. The strength of the effect is smaller in patients with more severe
      brain injury and depends on time of inclusion in a study.

PMID- 21904254
TI  - Image-guided thoracoscopic resection of thoracic dumbbell nerve sheath tumors.
AB  - BACKGROUND: Surgical removal of dumbbell nerve sheath tumors (NSTs) remains
      challenging because these neoplasms occupy >= 2 spinal and extraspinal spaces.
      The presence of intraspinal extension, tumor dimension, and/or its location
      within the thoracic cavity have previously made the resection of these types of
      neoplasms difficult. OBJECTIVE: To describe the feasibility of performing
      minimally invasive thoracoscopic surgery, as facilitated by an image guidance
      system (IGS), to achieve gross total resection of select dumbbell NSTs located in
      the thoracic spine. METHODS: The 3 cases presented here contained small
      intraspinal or foraminal components. Preoperative symptoms included Horner
      syndrome and back and chest wall pain. We used IGS to help guide the complete
      thoracoscopic resection of select dumbbell NSTs, consisting of extradural,
      intraforaminal, and paravertebral tumor components, which previously would have
      been challenging with only a thoracoscopic approach. RESULTS: IGS provided
      continuous intraoperative anatomic orientation to achieve gross total resection
      in all 3 cases. All surgical and postsurgical outcomes were satisfactory;
      preoperative symptoms improved or resolved; and no adverse events were observed.
      CONCLUSION: Thoracic dumbbell NSTs that have small intraspinal or foraminal
      components could be resected thoracoscopically when facilitated by IGS. Image
      guided thoracoscopic resection of such dumbbell tumors may not only improve the
      precision of resection, reduce recurrence, and avoid the need for spinal
      reconstruction but also obviate the need for more invasive or simultaneous
      posterior procedures. The IGS enhances the accuracy and safety of 2-dimensional
      thoracoscopic surgery and may reduce its learning curve.

PMID- 21904255
TI  - Internal jugular vein compression mitigates traumatic axonal injury in a rat
      model by reducing the intracranial slosh effect.
AB  - BACKGROUND: Traumatic brain injury (TBI) remains a devastating condition for
      which extracranial protection traditionally has been in the form of helmets,
      which largely fail to protect against intracranial injury. OBJECTIVE: To
      determine whether the pathological outcome after traumatic brain injury can be
      improved via slosh mitigation by internal jugular vein (IJV) compression.
      METHODS: Two groups of 10 adult male Sprague-Dawley rats were subjected to impact
      acceleration traumatic brain injury. One group underwent IJV compression via
      application of a collar before injury; the second group did not. Intracranial
      pressure and intraocular pressure were measured before and after IJV compression
      to assess collar performance. All rats were killed after a 7-day recovery period,
      and brainstem white matter tracts underwent fluorescent immunohistochemical
      processing and labeling of beta-amyloid precursor protein, a marker of axonal
      injury. Digital imaging and statistical analyses were used to determine whether
      IJV compression resulted in a diminished number of injured axons. RESULTS:
      Compression of the IJV resulted in an immediate 30% increase in intraocular and
      intracranial pressures. Most notably, IJV compression resulted in > 80% reduction
      in the number of amyloid precursor protein-positive axons as indicated by
      immunohistochemical analysis. CONCLUSION: Using a standard acceleration
      deceleration laboratory model of mild traumatic brain injury, we have shown
      successful prevention of axonal injury after IJV compression as indicated by
      immunohistochemical staining of amyloid precursor protein. We argue that IJV
      compression reduces slosh-mediated brain injury by increasing intracranial blood
      volume, which can be indirectly measured by intracranial and intraocular
      pressures.

PMID- 21904257
TI  - epsilon-Aminocaproic acid in angiographically negative subarachnoid hemorrhage
      patients is safe: a retrospective review of 83 consecutive patients.
AB  - BACKGROUND: epsilon-Aminocaproic acid (EACA) has been used to reduce the rate of
      cerebral aneurysm rerupture before definitive treatment. In centers administering
      EACA to patients with a subarachnoid hemorrhage (SAH), patients eventually
      diagnosed with angiographically negative subarachnoid hemorrhage (ANSAH) may also
      initially receive EACA, perhaps placing them at increased risk for ischemic
      complications. OBJECTIVE: To evaluate the effect of short-term EACA on outcomes
      and secondary measures in patients with ANSAH. METHODS: We conducted a
      retrospective study of 454 consecutive SAH patients over a 2-year period under a
      current protocol for EACA use. Patients were excluded if a source for the SAH was
      discovered, yielding a total of 83 ANSAH patients. The patients were assigned to
      groups that did or did not receive EACA. The primary end points of the study were
      ischemic complications, pulmonary emboli, vasospasm, ventriculoperitoneal
      shunting rates, and outcomes. RESULTS: Statistical analysis yielded no
      significant difference between the 2 arms with respect to any of the end points:
      vasospasm (P = .65), deep vein thrombosis (P = .51), pulmonary embolism (P =
      1.0), stroke (P = 1.0), myocardial infarction (P = 1.0), and ventriculoperitoneal
      shunt (P = .57). There was no statistically significant outcome difference using
      the modified Rankin Scale (P = .30). CONCLUSION: Short-term (<72 hour)
      application of EACA does not result in an increase in adverse events in patients
      with ANSAH.

PMID- 21904258
TI  - The middle fossa approach and extended middle fossa approach:  technique and
      operative nuances.
AB  - BACKGROUND: The middle fossa approach and extended middle fossa approach, also
      known as the anterior transpetrosal approach, are cranial base techniques for
      addressing small vestibular schwannomas, medial temporal bone lesions, midbasilar
      trunk aneurysms, and selected petroclival lesions. OBJECTIVE: To provide an
      outline of a number of technical nuances that are important to correct
      application of these approaches, maximizing exposure, and limiting potential
      morbidity. METHODS: Via a temporal craniotomy, the petrous apex is removed in
      variable degrees, depending on the exposure requirements of the lesion. The
      technique is described in detail with appropriate nuances of the technique
      provided. RESULTS: The described nuances of technique in the performance of the
      approaches have resulted in successful application of these techniques in a
      significant number of cases. CONCLUSION: Significant familiarity and practice
      with these surgical approach techniques are critical to applying them safely to
      clinical problems. A number of technical details can assist the surgeon in
      achieving optimal exposure and limited morbidity.

PMID- 21904259
TI  - Delayed intracerebral hemorrhage after uneventful embolization of brain
      arteriovenous malformations is related to volume of embolic agent administered: 
      multivariate analysis of 13 predictive factors.
AB  - BACKGROUND: The mechanisms and management of delayed intracerebral hemorrhage
      (dICH) after treatment of brain arteriovenous malformations (AVMs) are poorly
      understood and widely debated. Many clinical predictive factors have been
      theorized for dICH after an otherwise uneventful AVM embolization, but there is
      an absence of data to discern their significance. OBJECTIVE: To analyze 13
      proposed predictive factors and to assess their potential in guiding prevention
      strategies. METHODS: One hundred sixty-eight embolization procedures were
      performed on 67 patients with brain AVMs by a single surgeon. Patients were
      divided into 2 groups: those with symptomatic dICH and control subjects. Thirteen
      factors were analyzed: age, sex, race, previous ICH, Spetzler-Martin grade, AVM
      size, eloquence, embolic volume, embolic agent, percent obliteration, and timing,
      number, and stage of embolizations. Univariate and multivariate analyses were
      performed on these factors to determine significance. RESULTS: Six procedures
      were complicated by dICH; 5 (83%) occurred after the final planned procedure. The
      volume of embolic agent was significantly higher in the dICH group (4.5 +/- 1.0
      mL) compared with control subjects (1.7 +/- 0.2 mL) in both univariate and
      multivariate analyses (P < .01), even after controlling for AVM size. AVM size
      was significant in univariate analysis but not multivariate analysis. There were
      no statistically significant differences between the groups for any of the other
      possible predictive factors. CONCLUSION: High volume of embolic agent
      administered per procedure is an independent predictive factor for dICH. Limiting
      the injected volume for each procedure may reduce this poorly understood
      complication.

PMID- 21904260
TI  - Microplate-bridge technique for watertight dural closures in the combined
      petrosal approach.
AB  - BACKGROUND: Although the combined petrosal approach has significant advantages
      for medium to large petroclival lesions, it carries the risk of a few major
      complications. The cerebrospinal fluid leak rate with this approach has been
      reported to be as high as 15%. OBJECTIVE: To describe an innovative technique of
      watertight dural closure with a long microplate-bridge technique for the combined
      petrosal approach. METHODS: We describe our method of watertight dural closures
      with the microplate-bridge technique for combined petrosal approaches using
      cadaveric heads and clinical cases. We review our postoperative outcomes in
      respect to cerebrospinal fluid leaks. RESULTS: The technique involves a fascial
      graft to the presigmoid-subtemporal defect, fixated with a long microtitanium
      plate over the cranial base side. The fascial graft is augmented by covering it
      with an abdominal fat graft and a vascularized pericranial flap. This technique
      was performed in 23 patients after surgical resection of petroclival meningiomas
      with only 1 postoperative cerebrospinal fluid leak (4.4%). CONCLUSION: We
      recommend this safe and simple closure technique during skull base surgery.

PMID- 21904261
TI  - Analysis of nonmodifiable risk factors for intracranial aneurysm rupture in a
      large, retrospective cohort.
AB  - BACKGROUND: The risk factors predictive of intracranial aneurysm rupture remain
      incompletely defined. OBJECTIVE: To examine the association between various
      nonmodifiable risk factors and aneurysm rupture in a large cohort of patients
      evaluated at a single institution. METHODS: A retrospective analysis of patients
      admitted to a cerebrovascular facility between January 2006 and 2010 with a
      primary diagnosis of cerebral aneurysm. Aneurysms were divided into 2 groups:
      unruptured or ruptured. The dome diameter, aspect ratio (AR), location,
      sidedness, neck morphology, and multiplicity were entered into a central
      database. A full model was constructed, and a systematic removal of the least
      significant variables was performed in a sequential fashion until only those
      variables reaching significance remained. RESULTS: We identified 2347 patients
      harboring 5134 individual aneurysms, of which 34.90% were ruptured and 65.09%
      were unruptured. On admission, 25.89% of aneurysms with a dome diameter <10 mm
      and 58.33% of aneurysms with a dome >10 mm were ruptured (P < .001). Of aneurysms
      with an AR >1.6, 52.44% presented following a rupture (P < .001). The highest
      incidence of rupture (69.21%) was observed in aneurysms with an AR >1.6, dome
      diameter <10 mm, and a deviated neck. Deviated neck-type aneurysms had a
      significantly greater incidence of rupture than classical neck-type aneurysms (P
      < .001). CONCLUSION: An AR >1.6, dome diameter >10 mm, a deviated neck, and right
      sidedness are independently associated with aneurysm rupture.

PMID- 21904262
TI  - Carotid endarterectomy with primary closure:  analysis of outcomes and review of
      the literature.
AB  - BACKGROUND: Despite abundant published support of patch angioplasty during
      carotid endarterectomy (CEA), primary closure is still widely used. The reasons
      underlying the persistence of primary closure are not quite evident in the
      literature. OBJECTIVE: To present our experience with primary closure in CEA, and
      provide a rationale for its persistent wide use. METHODS: Medical records of all
      patients undergoing CEA by the senior author (R.F.) were retrospectively
      reviewed. Follow-up was supplemented with a telephone interview and completion of
      a structured questionnaire. A review of the current literature was performed.
      RESULTS: From 1998 to 2010, the senior author performed 111 CEAs. Average cross
      clamp time was 33 +/- 11 minutes. Postoperative complications included 1 non-ST
      elevation myocardial infarction and 2 strokes. No deaths, cranial-nerve deficits,
      or acute reocclusions were observed. After a mean follow-up of 64.6 months
      (7170.6 case-months), there were 3 contralateral strokes and 7 deaths. There were
      no ipsilateral strokes or restenoses >50%. Follow-up medication compliance was
      94.6% for antiplatelet agents and 91.9% for statins. The outcomes of the current
      study were comparable to those of the available trials comparing patch
      angioplasty with primary closure. A careful evaluation of the literature revealed
      a number of reasons potentially explaining the persistent use of patch
      angioplasty. CONCLUSION: In conjunction with contemporary medical management,
      primary closure during CEA may yield results comparable or superior to patch
      angioplasty. Advantages of primary closure include shorter cross-clamp times and
      elimination of graft-specific complications.

PMID- 21904263
TI  - Risk factors for posttreatment edema in patients treated with stereotactic
      radiosurgery for meningiomas.
AB  - BACKGROUND: Peritumoral edema is a recognized complication following stereotactic
      radiosurgery (SRS). OBJECTIVE: To evaluate the risk of posttreatment peritumoral
      edema following SRS for intracranial meningiomas and determine predictive
      factors. METHODS: Between 2002 and 2008, 173 evaluable patients underwent
      CyberKnife or Gamma Knife SRS for meningiomas. Eighty-four patients (49%) had
      prior surgical resections, 13 patients had World Health Organization grade II
      (atypical) meningiomas, and 117 patients had a neurological deficit before SRS.
      Sixty-two tumors were in parasagittal, parafalcine, and convexity locations. The
      median tumor volume was 4.7 mL (range, 0.1-231.8 mL). The median prescribed dose
      and median prescribed biologically equivalent dose were 15 Gy (range, 9-40 Gy)
      and 67 Gy (range, 14-116 Gy), respectively. Ninety-seven patients were treated
      with single-fraction SRS, 74 received 2 to 5 fractions, and 2 received >5
      fractions. RESULTS: The median follow-up was 21.0 months. Thirteen patients (8%)
      developed symptomatic peritumoral edema, with a median onset time of 4.5 months
      (range, 0.2-9.5 months). The 3-, 6-, 12-, and 24-month actuarial symptomatic
      edema rates were 2.9%, 4.9%, 7.7%, and 8.5%, respectively. The crude tumor
      control rate was 94%. On univariate analysis, large tumor volume (P = .01) and
      single-fraction SRS (P = .04) were predictive for development of posttreatment
      edema. CONCLUSION: SRS meningioma treatment demonstrated a low incidence of
      toxicity; however, large tumor volumes and single-fraction SRS treatment had an
      increased risk for posttreatment edema. Risk factors for edema should be
      considered in meningiomas treatment.

PMID- 21904264
TI  - Epilepsy surgery of the temporal lobe in pediatric population:  a retrospective
      analysis.
AB  - BACKGROUND: There is still some reluctance to refer pediatric patients for
      epilepsy surgery, despite evidence of success in retrospective series. OBJECTIVE:
      To describe surgical experience and long-term outcome in pediatric temporal lobe
      epilepsy (TLE) at a single institution. METHODS: Retrospective review of
      pediatric (<18-years-old) TLE patients who underwent surgery between November
      1996 and December 2006 at Cleveland Clinic Epilepsy Center. Cox proportional
      hazard modeling was used to assess outcome predictors. RESULTS: One hundred
      thirty pediatric patients met study criteria. Mean time between seizure onset and
      surgery was 6.3 years. Invasive evaluation was used in 32 patients (24.5%).
      Hippocampal sclerosis was present in 70 patients (53.8%), either alone or
      associated in dual pathology. The complication rate was 7%. The seizure-freedom
      rates at 1, 2, 5, and 12 years were 76%, 72%, 54%, and 41%, respectively (Kaplan
      Meier). With the use of the Engel outcome classification, 98 (75.3%) patients
      were class I, 11 (8.5%) class II, 9 (7%) class III, and 12 (9.2%) were class IV
      at last follow-up. Only 4 (3.1%) patients underwent reoperations. Antiepileptic
      drugs (AEDs) were discontinued in 36 patients (28.3%) in a mean period of 18
      months (SD +/- 17 months; range, 6-102 months). Although left-sided resection,
      lower number of preoperative AED trials (<= 4), and tumor pathology correlated
      with favorable seizure outcomes, extensive surgical resection remained the only
      significant outcome predictor after multivariate analysis (P = .007; HR = 0.13
      [95% confidence interval 0.007-0.64]). CONCLUSION: Careful selection of surgical
      candidates by multidisciplinary evaluations is required. Long-term seizure
      control is achieved successfully with acceptable low complication rates.

PMID- 21904265
TI  - Frederic Gibbs and his contributions to epilepsy surgery and
      electroencephalography.
AB  - Frederic Gibbs' (1903-1992) long research career was devoted to the understanding
      and treatment of epileptic phenomena and closely associated with the development
      of electroencephalography (EEG). After medical school, he joined the Harvard
      Neurological Unit at Boston City Hospital directed by Stanley Cobb. In the early
      1930s, Gibbs developed a thermoelectric blood flow probe and, with William
      Lennox, proved in animals and humans that a seizure increases cerebral blood
      flow. By 1934, Gibbs became a pioneer in the field of EEG while working at
      Harvard with Hallowell Davis and Lennox, and was the first to convincingly record
      and report EEG findings in epilepsy and states of altered consciousness. Several
      years later, Gibbs and Lennox were the first to recommend cerebral excisions in
      several patients with uncontrolled epilepsy based on EEG. Moving to the
      University of Illinois at Chicago in 1944, Gibbs founded a consultation clinic
      for epilepsy, performed the first EEG depth recordings using
      pneumoencephalography-guided stereotaxy, and noted that sleep EEGs in patients
      with psychomotor seizures frequently disclosed temporal epileptic patterns. Gibbs
      convinced Percival Bailey to collaborate on patients with refractory temporal
      lobe psychomotor seizures without tumors. In 1947, the first nonlesional temporal
      lobe excisions based on EEG localization were performed in these patients, and,
      by 1948, anterior temporal lobectomy had become their procedure of choice. Gibbs
      and Lennox received the coveted Lasker Award among other honors as pioneers in
      establishing the modern era of epilepsy diagnosis and treatment.

PMID- 21904266
TI  - Management of residual and recurrent aneurysms after initial endovascular
      treatment.
AB  - BACKGROUND: Coil instability possibly translating into higher delayed rebleeding
      rates remains a concern in the endovascular management of cerebral aneurysms.
      OBJECTIVE: To report on 127 patients with endovascular aneurysmal remnants who
      underwent re-treatment over an 18 year period. METHODS: Patients presenting with
      aneurysm residuals >20% of the original lesion, unstable neck remnants,
      aneurysmal regrowth, or new aneurysmal daughter sacs were treated by an
      individualized approach, using both endovascular and surgical techniques.
      RESULTS: Seventy-five aneurysmal remnants (59.1%) were treated by further re
      embolization. Standard coil embolization was used in 65 cases, stent-protected
      coiling in 9 cases, and balloon remodeled coiling in 1 case, respectively. Fifty
      two (40.9%) aneurysmal remnants were treated surgically. Standard microsurgical
      clipping was used in 44 patients, parent artery occlusion or trapping under
      bypass protection in 5 cases, deliberate clipping of the basilar artery trunk in
      2 cases, and aneurysm wrapping in one case, respectively. Mechanisms of aneurysm
      recurrence were coil compaction in 93 cases and regrowth in 34 cases. A single
      reembolization was sufficient to occlude 78.7% of recurrences from coil
      compaction, but only 14.3% of recurrences from aneurysm regrowth. CONCLUSION: The
      individualized approach resulted in complete occlusion of 114 aneurysms (89.7%),
      with neck remnants and residual aneurysms detectable in 11 (8.7%) and 2 (1.6%)
      cases, respectively. Treatment morbidity was 11.9%, without significant
      differences between surgical (15.6%) and endovascular (9.3%) patients (P = .09).
      Recurrences from coil compaction were safely treated by re-embolization, whereas
      recurrences from aneurysmal regrowth may best be managed surgically when
      technically feasible.

PMID- 21904267
TI  - Gamma knife thalamotomy for Parkinson disease and essential tremor:  a
      prospective multicenter study.
AB  - BACKGROUND: No prospective study of gamma knife thalamotomy for intractable
      tremor has previously been reported. OBJECTIVE: To clarify the safety and
      optimally effective conditions for performing unilateral gamma knife (GK)
      thalamotomy for tremors of Parkinson disease (PD) and essential tremor (ET), a
      systematic postirradiation 24-month follow-up study was conducted at 6
      institutions. We present the results of this multicenter collaborative trial.
      METHODS: In total, 72 patients (PD characterized by tremor, n = 59; ET, n = 13)
      were registered at 6 Japanese institutions. Following our selective thalamotomy
      procedure, the lateral part of the ventralis intermedius nucleus, 45% of the
      thalamic length from the anterior tip, was selected as the GK isocenter. A single
      130-Gy shot was applied using a 4-mm collimator. Evaluation included neurological
      examination, magnetic resonance imaging and/or computerized tomography, the
      unified Parkinson's disease rating scale (UPDRS), electromyography, medication
      change, and video observations. RESULTS: Final clinical effects were favorable.
      Of 53 patients who completed 24 months of follow-up, 43 were evaluated as having
      excellent or good results (81.1%). UPDRS scores showed tremor improvement (parts
      II and III). Thalamic lesion size fluctuated but converged to either an almost
      spherical shape (65.6%), a sphere with streaking (23.4%), or an extended high
      signal zone (10.9%). No permanent clinical complications were observed.
      CONCLUSION: GK thalamotomy is an alternative treatment for intractable tremors of
      PD as well as for ET. Less invasive intervention may be beneficial to patients.

PMID- 21904268
TI  - Cause of apical thinning on attenuation-corrected myocardial perfusion SPECT.
AB  - OBJECTIVES: Decreases in apical and apex activities - namely, 'apical thinning' -
      are a well-known phenomenon in attenuation-corrected (AC) myocardial perfusion.
      The aim of this study was to compare actual myocardial thickness derived from a
      multidetector-row computed tomography with AC myocardial perfusion count from a
      hybrid single-photon emission computed tomography/computed tomography to
      investigate the cause of apical thinning. METHODS: We enrolled 21 participants
      with a low likelihood of coronary artery disease (mean age 65 +/- 21 years, 13
      men) from 185 consecutive patients and 11 healthy volunteers, who independently
      underwent 99mTc-sestamibi single-photon emission computed tomography/computed
      tomography and 64-slice multidetector-row computed tomography scans. AC and non
      AC myocardial perfusion counts and thickness were measured on the basis of a 17
      segment model and averaged at the apex, apical, mid, and basal walls. RESULTS:
      Myocardial thickness at the apex was significantly thinner than that at the
      apical and mid walls (5.1 +/- 1.3, 7.3 +/- 1.3, and 9.9 +/- 2.4 mm, respectively;
      P<0.005). AC count at the apex was significantly lower than that at the apical
      and mid regions (76.0 +/- 5.5, 82.8 +/- 4.7, and 85.6 +/- 3.8, respectively;
      P<0.002). Moderate relationship was observed between myocardial thickness and AC
      count (y=-10.5 + 0.22x, r=0.54, P<0.0001. No relationship was found between
      thickness and non-AC count (r=0.16, P=0.263). CONCLUSION: The low apex and apical
      counts were caused by anatomical thinning of the myocardium in AC myocardial
      perfusion imaging. Attenuation correction provided an accurate relationship
      between myocardial count and thickness because of the partial volume effect.

PMID- 21904269
TI  - Epidemiology of cytomegalovirus infection after pancreas transplantation.
AB  - BACKGROUND: Epidemiology of cytomegalovirus (CMV) infection has not been
      comprehensively studied after all three types of pancreas transplant (PT)
      including simultaneous pancreas-kidney transplantation (SPK), pancreas
      transplantation alone (PTA), and pancreas after kidney transplantation (PAK).
      METHODS: We evaluated incidence, risk factors, and outcomes of CMV infection
      after pancreas transplant at our center from January 1, 1998, to December 31,
      2009. RESULTS: The study cohort included 252 recipients (SPK 60, PTA 71, and PAK
      121), 53% men, age 43.9+/-9 years, followed for 6.3 (interquartile range 3-9)
      years. CMV serostatus was donor (D) seropositive and recipient (R) seronegative
      (D+/R-) (27%), D+/R+ (32%), D-/R+ (18%), D-/R- (23%), and one unknown/R+ (0.4%).
      Two hundred six (82%) patients received CMV prophylaxis. Twelve patients
      experienced CMV viremia, whereas 31 developed CMV disease. The cumulative
      incidence of CMV infection (viremia and disease) was 15%, 17%, and 20% at 1, 5,
      and 10 years, respectively, with no events after 10 years. It was higher in D+/R-
      group (P<0.004) and patients with kidney graft failure (P=0.036). The variables
      significantly associated with pancreas graft failure were transplant type (PTA
      vs. SPK, hazard ratio [HR]=2.29, P=0.020; PAK vs. SPK, HR=2.73, P=0.003) and
      acute pancreas rejection (HR=2.47, P<0.001). In multivariable mortality model,
      increased age (P<0.001) and pancreas graft failure (P<0.001) were associated with
      an increased risk of death, whereas CMV infection (P=0.036) was associated with a
      borderline decreased risk. CONCLUSIONS: CMV remains a common cause of clinical
      illness, particularly among the CMV D+/R- mismatched and patients with kidney
      graft failure. Marginal association was observed between CMV infection and a
      lower risk of death, but not with allograft failure.

PMID- 21904270
TI  - Synthesis and chemical characterisation of some new diheteroaryl thienothiophene
      derivatives.
AB  - Treatment of 1-(5-acetyl-3,4-dimethythieno[2,3-b]thiophene-2yl)ethanone (1) with
      dimethylformamide dimethyl acetal afforded enaminone derivative 2, which reacted
      with amino derivatives to give the corresponding bis-pyrimidine, bis-pyrazole,
      bis-triazolo-pyrimidine and bis-benzoimidazopyrimidine derivatives.

PMID- 21904271
TI  - Crystal structure and density functional theory study on structural properties
      and energies of a isonicotinohydrazide compound.
AB  - An X-ray and a theoretical study of the structure of the isoniazid derivative N'
      (4-dimethylaminobenzylidene)-isonicotinohydrazide monohydrate (1) are reported.
      In this work, we will report a combined experimental and theoretical study on the
      molecular structure, vibrational spectra and energies of N'-(4
      dimethylaminobenzylidene)-isonicotinohydrazide monohydrate. The calculated
      parameters are in good agreement with the corresponding X-ray diffraction values.
      The FTIR spectrum in the range of 400-4000 cm-1 of N'-(4
      dimethylaminobenzylidene)-isonicotinohydrazide monohydrate has been recorded. The
      molecular geometry and vibrational frequencies and energies in the ground state
      are calculated by using the DFT (B3LYP, PBE1PBE) methods with 6-311G** basis
      sets. The calculated HOMO and LUMO energies also confirm that charge transfer
      occurs within the molecule. The geometries and normal modes of vibrations
      obtained from B3LYP/PBE1PBE/6-311G** calculations are in good agreement with the
      experimentally observed data.

PMID- 21904272
TI  - Chemical composition and possible in vitro phytotoxic activity of Helichrsyum
      italicum (Roth) Don ssp. italicum.
AB  - The chemical composition of the essential oil of Helichrysum italicum (Roth) Don
      ssp. italicum, collected in the National Park of Cilento and Diano Valley,
      Southern Italy, was studied by means of GC and GC/MS. Forty four compounds of 45
      constituents were identified in the oil, mainly oxygenated sesquiterpenes. The
      essential oil was evaluated for its potential in vitro phytotoxic activity
      against germination and early radicle elongation of radish and garden cress. The
      radicle elongation of radish was significantly inhibited at the highest doses
      tested, while germination of both seeds was not affected.

PMID- 21904273
TI  - Lower extremity biomechanics during kendo strike-thrust motion in healthy kendo
      athletes.
AB  - AIM: The aim of this study was to demonstrate the kinematics and kinetics of the
      lower extremity during the kendo strike-thrust motion in experienced kendo
      athletes. METHODS: Fifteen experienced kendo athletes (age 20.4+/-1.2 years;
      height 171.5+/-4 cm; weight 73.9+/-9.1 kg; the kendo experience 11.1+/-3.1 years)
      volunteered to participate in the study. The three-dimensional kinematic and
      kinetic data was collected by the motion analysis system with eight cameras and
      with a force platform. We instructed the participants to perform three sets of
      kendo motion at the distances of 1.8 m, 2 m, and 2.2 m to the target. We then
      obtained the joint kinematic and kinetic data of the ankle dorsiflexion
      planterflexion, foot pronation-supination, knee flexion-extension, and hip
      flexion-extension during the single support phase. The peak foot pronation angle
      and the range of motion (ROM) of foot pronation were also calculated. RESULTS:
      The result demonstrated the high intra-subject repeatability of the joint angle
      and the torque curve of the left lower extremity during the single support phase
      in the kendo motion. Our result also showed that as for the peak foot pronation
      angle and the pronation ROM there was no significant difference between different
      distances to the target. CONCLUSION: We provided the basic biomechanical
      information during the kendo strike-thrust motion, and the result will help us to
      understand the Achilles tendon injury occurrence in kendo athletes.

PMID- 21904274
TI  - Kinematic analysis of kicking in young top-class soccer players.
AB  - AIM: The aim of this study was to describe the kinematic pattern of the kicking
      movement of young top-class soccer players focusing in examining the linear joint
      markers velocity of the leg kick and the segments angular position. METHODS:
      Maximal in step kicks performed by 21 young top-class soccer players (16.1 +/-
      0.2 years) were analyzed using a three dimensional motion capture system.
      RESULTS: The ball was released at a mean velocity of 30.6 +/- 1.54 m/s. The
      maximum linear velocity of the hip (5.49 +/- 0.53 m/s), knee (10.89 +/- 0.63
      m/s), ankle (19.36 +/- 0.96 m/s) and toe (24.59 +/- 1.33 m/s) joint markers were
      achieved consecutively during the kick, representing a typical proximal to distal
      kinetic chain. Significant (P<0.01) differences in the arms, trunk, thigh, shank
      and foot segments angular positions were found among the instant times in which
      the key events took place, determined by the maximum velocity of the hip (T1),
      knee (T2), ankle (T3) and toe (T4) joint markers (except between T3 and T4). This
      fact indicates that the instant time when each joint marker reached its maximum
      velocity implied different positions of the body segments. CONCLUSION: The
      results of this study provide additional data about the kicking biomechanics of
      young top-class soccer players. This information should be taken in consideration
      by coaches that train young soccer players.

PMID- 21904275
TI  - Can the official soccer game be considered the most important contribution to
      player's physical fitness level?
AB  - AIM: During competitive soccer match play, elite players are subdued to vigorous
      physical and psychological strains. Thus, some changes in overall physical
      fitness can be expected. The objective of this paper was to determine whether
      official games influence physical fitness in soccer players. METHODS: The
      participants were divided according to the number of minutes spent in the game as
      well as according to some additional criteria into starters (STA; N.=33, >1000
      minutes spent in the official game) and non-starters (NON; N.=31, <1000 minutes
      spent in the official game). Both groups participated in the initial (end of pre
      season) and in the final testing procedures (one week after the end of the
      competition period). The total of 24 variables covered players' power
      performance, kicking the ball, aerobic capacity, agility and flexibility.
      RESULTS: The STA group showed positive significant differences (P<0.05) from the
      NON group in 21 out of 24 variables. The most significant findings of this study
      point to the fact that official games help in maintaining and improving agility
      parameters (6 out of 7 tests) as well as in maintaining and improving overall
      power performance of soccer players which includes sprinting, jumping and kicking
      the ball. CONCLUSION: Due to specific physiological and psychological factors,
      official matches make it possible for the starters to develop the mentioned
      aspects to a higher level when compared to the non-starting team colleagues.

PMID- 21904276
TI  - Effect of maximal and slow versus recreational muscle contractions on energy
      expenditure in trained and untrained men.
AB  - AIM: The primary purpose of this study was to compare energy expenditure among
      resistance exercise protocols using maximally explosive or slow contractions
      versus recreational in trained and untrained men. METHODS: Seven trained (21.9+/
      2.1 yrs) and seven untrained men (20.1+/-2.2 yrs) performed three nearly
      identical exercise protocols, and a no-exercise (CONTROL) session in a randomly
      assigned, counterbalanced order. Subjects performed three sets of squats,
      dumbbell-row, deadlift, bench press, lat-pulldown, shoulder press, arm curls and
      dips using either recreational (REC), 2s (SLOW) or maximally explosive
      contractions (MAX). Expired air was collected continuously for 15 min before, ~37
      43 min during, and 2 hr postexercise. Finger prick samples (25 uL) were collected
      and analyzed for blood lactate (BL) (mmol.L-1) before, immediately after, and
      during 120 min of recovery. RESULTS: Rates of energy expenditure were
      significantly (P<=0.05) greater for MAX than SLOW and REC during all exercises
      and +5 min after exercise in trained men, and MAX was greater than REC during all
      exercises except deadlift in untrained men. In trained men, total kcal were
      significantly greater (P<=0.05) with MAX (507+/-48) compared to REC (431+/-47),
      but not in untrained. Conversely, BL was significantly greater (P<=0.05) after
      SLOW compared to REC in trained and untrained men, while BL was only greater
      after MAX versus REC in trained men. CONCLUSION: For whole-body resistance
      exercise programs, maximally explosive contractions optimize energy expenditure
      in trained men, but slow contractions are recommended for untrained exercisers.
      Therefore, contraction intensity should be considered a program design variable
      for exercise prescriptions aimed to improve general health and fitness.

PMID- 21904277
TI  - Aerobic training programs and glycemic control in diabetic children in relation
      to exercise frequency.
AB  - AIM: The aim of this study was to assess the effect of an aerobic training on
      glycemic control and lipid profile in diabetic children. METHODS: Thirty-three
      children with type 1 diabetes mellitus (T1DM) were equally divided in three
      groups. The control group (CG) did not perform any training intervention during
      the period of the investigation and the subjects were instructed to continue with
      their daily lifestyle patterns. The second group (G1) and the third group (G2)
      completed a six-month aerobic training programs. During the period of the
      investigation, G1 participated in one daily session (~60 min) of aerobic exercise
      twice weekly, while G2 performed in the form of daily session four times a week
      (~60 min). HbA1c and lipid profile were measured before training intervention,
      then after three and six months. RESULTS: The three-month periods was without
      significant changes of HbA1c in the two groups but significantly increased high
      density lipoprotein cholesterol (HDL-C) in G1 (P<0.05). In G2, an increase of HDL
      C was accompanied by a decrease of serum triglyceride (TG) (P<0.05). After six
      months, only HDL-C and TG levels were significantly lower in G1 (P<0.01), while
      in G2 HDL-C increased (68.8+/-5.7 mg/dL vs. 56.7 +/-7.2 mg/dL; P<0.01), low
      density lipoprotein cholesterol (LDL-C) (69.2+/-8.5 mg/dL vs. 81.6+/-11.8 mg/dL;
      P<0.01), TG concentrations decreased (60.7+/-6.9 mg/dL vs. 77.4+/-9.3 mg/dL;
      P<0.01) and HbA1c was significantly lower (6.8+/-1.1% vs. 8.2+/-1.5%; P<0.05),
      comparatively to those before training. CONCLUSION: However, the six-month
      periods showed that children exercising more than two times weekly significantly
      improved HbA1c and lipid profile. These results must encourage children with T1DM
      to regularly practice sporty activities for long periods.

PMID- 21904278
TI  - Effect of a five-toed minimal protection shoe on static and dynamic ankle
      position sense.
AB  - AIM: The main aim of this study was to test the hypothesis that the
      VibramFivefingers model, with its minimal structure, cushioning and finger
      separation, allows a more accurate estimate of static and dynamic foot position
      compared to wearing a standard cushioned running shoe. METHODS: Static ankle
      joint position sense was assessed in the sagittal and frontal plane by asking
      fourteen healthy experienced amateur runners to estimate the perceived direction
      and amplitude of a support slope surface board placed under their right foot
      while standing. The dynamic measures were performed with the subjects running on
      a treadmill at 12 km/h and asking them to evaluate the treadmill surface slope.
      Two footwear (Fivefingers and a cushioned protective running shoe) and the
      barefoot condition were compared. RESULTS: Plantarflexion, dorsiflexion, eversion
      and inversion movements were underestimated in all the experimental conditions.
      In the static trials there was significantly more angle error underestimation
      (P<0.05) with the running shoe, while no significant differences were found
      between Fivefingers and barefoot condition. While running, the treadmill surface
      slope was significantly better estimated with Fivefingers than in the other two
      conditions (P<0.05). CONCLUSION: The data support the assumption that with
      Fivefingers is more likely to get a more correct estimation of the surface slope
      while standing and running compared to using a standard cushioned running shoe.
      The finding that the cushioned shoes significantly impair foot position awareness
      compared to less structured shoes is consistent with the results of some previous
      studies on healthy and unhealthy subjects.

PMID- 21904279
TI  - Effects of training frequency on physical fitness in male prepubertal tennis
      players.
AB  - AIM: Aim of the present study was to test if training frequency determines
      physical fitness and fat mass accumulation in prepubertal male tennis players
      (TP). METHODS: Body composition scans (DXA), jump performance (SJ and CMJ) and 30
      m running speed tests were conducted in 24 TP (10.6 years) and 17 physically
      active boys. Tennis players were divided into two groups (TP5: playing 5 d/week,
      n.=14; TP2: playing 2 d/week, n.=10). RESULTS: Compared to TP5 and TP2, controls
      had more total body fat (+23-28%) and fat mass in the trunk (+42-43%) and legs
      (+13-19%), respectively (P<0.05). The relative VO2max was higher in TP2 (12%) and
      TP5 (15%) than in controls (P<0.001). A positive correlation was observed between
      weekly trainng hours and VO2max (r=0.42, P<0.05, N.=24). Compared to controls,
      TP5 and TP2 jumped higher in SJ and CMJ (P<0.05) and ran faster in the 30 m test
      (P<0.05). Similar VO2max, jumping heights and running speed times were observed
      between TP5 and TP2. After adjustment for the percentage of body fat and age, TPs
      reached higher VO2max values than controls, while differences in SJ, CMJ and 30 m
      did not reach statistical significance. CONCLUSION: Playing tennis 2 d/week at
      prepubertal ages was associated to enhanced aerobic power and reduced total and
      regional adiposity (trunk and legs) compared to non-active boys. Playing 5 d/week
      only has a small additional effect. TPs had also higher jumping and sprinting
      performance than the controls, although these differences were accounted for by
      the increased fat mass of the control boys.

PMID- 21904280
TI  - Sport-specific power assessment for rock climbing.
AB  - AIM: The popularity of rock climbing has resulted in a growing research base for
      the sport. However, at present there is a lack of sport-specific measures of
      performance in the field. The aim of this study was to examine the use of the
      powerslap test as a sport specific power measure. METHODS: The participants in
      this study were categorised into four different ability groups (novice,
      intermediate, advanced and elite) based on self reported lead grade. Two separate
      experiments were conducted to determine validity and reliability. The powerslap
      test was conducted on a revolution board with two variations - wide and narrow
      grip, for both sides of the body. The test started with the climber hanging at
      full extension from two holds from which a pull up movement was made releasing
      one hand to slap a scaled score board above. RESULTS: There was a significant
      relationship between powerslap scores and climbing ability (Left Wide: r=0.7,
      P<0.0005; right wide: r=0.69, P<0.0005; left narrow: r=0.73, P<0.0005; right
      narrow: r =0.72, P<0.0005). Further to this, scores on the powerslap narrow test
      were significantly differentiated by climber ability (LEFT: F(3,37)=15.74,
      P<0.0005; right: F(3,37)=12.16, P<0.0005). Limits of agreement and intra-class
      correlation indicated that the powerslap test is a reliable performance measure.
      CONCLUSION: According to the present findings the narrow grip variation of the
      powerslap test is a useful sport-specific power test that is related to climbing
      performance.

PMID- 21904281
TI  - Quality control of 157 whole body adiposity prediction formulae in age and
      activity matched men.
AB  - AIM AND METHODS: The physiological and clinical importance of body composition is
      part of public health, nutrition and Sports medicine. The most popular field
      method for estimating total body adiposity remains anthropometry separately or in
      formulae. The aim of this study was to verify the suitability of an absolute
      maximum out of more than 600 existing anthropometry equations estimating %
      adipose tissue (AT) in a cross validation with dual energy X-ray absorptiometry
      (DXA), bioelectrical impedance analysis (BIA) and hydrodensitometry (HD) on 74
      British male subjects (mean age 34.4+/-14.1) with different lifestyles
      corresponding to a maximum of populations the original formula was developed for.
      RESULTS: Pearson correlation coefficients, paired sample t-test and Bland and
      Altman plots where used for analyses. From the tested formulae, 19 correlated
      well (r>=0.70) and showed no significant difference (p>0.05) with BIA, 15 with
      DXA and only 12 with HD. The results show a better match of the predicted % AT by
      anthropometric equations with BIA then with DXA or HD. CONCLUSION: All results
      and conditions considered, this study suggest not to use HD nor anthropometric
      formulae to assess % AT in men for an individual estimation.

PMID- 21904282
TI  - The effect of player positional groups on the nature of tackles that result in
      tackle-related injuries in professional rugby league matches.
AB  - AIM: The aim of this study was to describe the effect of player positional groups
      on the nature of tackles that result in tackle-related injuries in professional
      rugby league matches. METHODS: Prospective observational epidemiology analyses
      for tackle-related injuries and video analyses for the nature of tackles were
      conducted for a single team in the National Rugby League (NRL) throughout the
      2007 and 2008 competitions for a total of 48 games. Risk ratios (RR) were
      calculated for comparisons between positional groups (adjustable, hit-up forwards
      or outside backs). RESULTS: The total missed match tackle-related injury rate was
      57.8 per 1 000 player hours. Hit-up forwards recorded significantly more total
      tackle-related injuries than outside backs (RR: 1.3; P=0.049), but not more than
      adjustables (RR: 1.0; P=0.922). Hit-up forwards recorded significantly more chest
      back tackle-related injuries than adjustables (RR: 6.0; P=0.008). Outside backs
      recorded significantly more tackle injuries as the ball carrier than the tackler
      (RR: 2.4; P=0.015) while adjustables recorded significantly more tackle injuries
      as the tackler than the ball carrier (RR: 1.8; P<0.001). Hit-up forwards had a
      higher incidence of contusions, and sprains while adjustables had a higher
      incidence of fracture/dislocations. There were no differences in injury severity
      between the positional groups. CONCLUSION: Player positional group had an effect
      on tackle-related injury type and injury site. Hit-up forwards and outside backs
      recorded more tackle-related injuries as a ball carrier than as a tackler, while
      in contrast, adjustables recorded more tackle-related injuries as the tackler
      than the ball carrier.

PMID- 21904283
TI  - Heart rate response to a standardized walking exercise in the Arctic circumpolar
      region in morning vs. evening during the polar night and midnight sun.
AB  - AIM: Awareness of daytime and/or seasonal variation in performance and exercise
      efficiency can be important for athletes and coaches in order to suitably plan
      training sessions and avoid over-training. The study goal was to evaluate and
      compare walking-speed and time-related heart rate (HR) responses to a walking
      task at two times of day and year. METHODS: Five healthy females (age 21-35
      years) performed 9 km outdoor walking at 09:00h and 18:00h on 4 consecutive days
      in a period without sunlight (January) and with continuous daylight (May).
      Walking speed, average-heart rate (HR) and peak-HR (as %HRmax) were compared
      across all exercise sessions. RESULTS: In January the subjects achieved a higher
      peak-HR when they trained in the evening vs. morning, while average-HR and
      walking speed were not modified significantly. In May they achieved a higher peak
      HR and kept a higher average-HR when they trained in the morning, under the same
      walking speed. In both training-times carried out in May, average-HR and peak-HR
      were lower compared with January, while the walking speed was unvaried.
      CONCLUSION: A lower exercise average and peak HR, that could potentially be a
      favourable condition for exercise conditioning, was observed at both daily test
      times in May vs. January, with overall lowest HR observed in May when exercise
      occurred at 18:00 h. These findings support the presence of both seasonal and
      time of day effects on HR responses to a standardized exercise.

PMID- 21904284
TI  - Systolic right ventricular adaptive changes in athletes as predictors of the
      maximal functional capacity: a pulsed tissue Doppler study.
AB  - AIM: The aim of this study was to extend the analysis of the systolic right
      ventricular (RV) adaptation to combined endurance and strength training, to
      assess the utility of tissue Doppler imaging in detecting the degree of these
      changes and to find independent RV predictors of the maximal functional capacity.
      METHODS: Standard Doppler and TDI were used to assess cardiac parameters at rest
      in 37 elite male athletes (16 wrestlers, 21 water polo players) and 20 sedentary
      subjects of similar age. Progressive maximal test on treadmill was used to assess
      VO2max. The obtained parameters were adjusted for HR, FFM, and BSA. RESULTS:
      Wrestlers showed higher VO2max than controls, but lesser than water polo players.
      RV diameter was larger in athletes. Right atrial pressure (RVE/e) was higher in
      water polo players than in other groups. Systolic function assessed by tricuspid
      annular plane systolic excursion (TAPSE) and RVs' was the highest in wrestlers.
      Global RV systolic parameters myocardial performance index (MPI) and preejection
      time/ejection time index (PET/ET) were similar. On multivariate analysis systolic
      parameters were independent predictors of VO2max only in wrestlers: RVs'
      (beta=3.18, P=0.001) and RV ET (beta=2.32, P=0.001). RVE/e' correlated with RVs'
      (r=-0.57, P=0.000). TAPSE correlated with RV ET (r=0.32, P=0.015) and RVs'
      (beta=0.28, P=0.033). CONCLUSION: Systolic function assessed by TAPSE and RVs'
      has more improved in less endurance athletes. RVs'and TDI ejection time predict
      VO2max in wrestlers, and possibly in other athletes with lesser right atrial
      pressure. TDI enables quantifying RV adaptation degree in athletes, but
      complementary to M-mode technique.

PMID- 21904285
TI  - Morphology and biochemical markers of people living with HIV/AIDS undergoing a
      resistance exercise program: clinical series.
AB  - This descriptive case study aimed at assessing body's composition and impact on
      biochemical markers of people living with HIV/AIDS (S1=male-1, S2=female-1)
      undergoing a four-month intervention program of resistance exercises. Was
      analyzed the lipid profile (total cholesterol, LDL, HDL and triglycerides serum),
      immunological parameters (CD4 and viral load/VL) and morphological parameters
      (body mass index BMI, waist/Hip/WHR, perimeters and skinfold). Blood samples and
      antropometric measures were obtained in the pre-exercise (pre-test) and
      immediately after (16 weeks) of exercise (post-test). An increase in HDL (38 pre,
      42 post), LDL (89.6 pre, 95 post) was noted for S1 and a decrease in HDL (33 pre,
      25 post) and LDL (121.6 pre, 121 post) for S2; a decrease in Triglyceride for S1
      (292 pre, 214 post) and increase for S2 (102 pre, 166 post). Total cholesterol
      increased for both subjects (186 pre, 261 post S1 and 175 pre, 179 post S2).
      there was a decrease in CD4 for S1 (598 pre, 577 post) and an increase for S2
      (748 pre, 1.071 post). With respect to viral load, we found that both subjects
      (S1 and S2) presented values below the minimum limit (pre and post test), with no
      significant changes. Body composition improved (LMpre S1=43.13% and S2=23.35% and
      LMpost S1=46.51 and S2=26.15%; BFpre S1=41.13 and S2=18.14% and BFpost S1=38.32
      and S2=14.77%), as did BMI (25.27 pre, 27.44 post S1) and (24.24 pre, 24.74 post
      S2). The resistance exercise program as base in this intervention model promoted
      a healthy state for HIV and AIDS patients and did not pose any health risks to
      them.

PMID- 21904286
TI  - Advising parents on physical activity for children between 0 and 5 years.
AB  - AIM: Physical activity is thought to have a crucial role to play in health,
      psychomotor development and habit formation for children between 0 and 5 years
      old. However, all children under 6 are not as active as recommended in the
      literature. OBJECTIVE: to provide physicians with some guidelines, based on the
      principle of Early Screening and Brief Intervention, in order to encourage
      parents with young sedentary children to be more active. METHODS: Literature
      review, development of a decision algorithm, analysis by professionals. Results:
      Data were gathered from Medline Pubmed, Cochrane Library, and the French Database
      in Public Health (any date to November 2009). Papers which did not give enough
      details (length, nature, etc.) on the advice were rejected and papers which dealt
      with a brief consultation, or with advice that was given either to a whole group
      of people, or that was given by several health professionals during the course of
      a personal coaching program. RESULTS: For instance, 1 492 hits were found after
      researching the terms screening and brief intervention on Medline, but there were
      only 12 when the research was run together with the terms (physical activity or
      active play or exercise) and primary care. A decision algorithm to advise parents
      was developed, based on Early Screening and Brief Intervention principle. This
      tool should be usable by every doctor in primary care. "Early screening" starts
      with the parents being asked questions concerning their young child's physical
      activity, and "Brief Intervention" is based on existing recommendations, as well
      as recent studies on the key factors linked to physical activity in very young
      children. CONCLUSION: The ESBI approach proved successful when applied to
      psychoactive substances and merits testing in the field of physical activity.
      Further studies are needed to provide doctors with efficient tools to evaluate
      physical activity during a consultation.

PMID- 21904287
TI  - Heart rate monitoring as a reliable tool for assessing energy expenditure in
      obese individuals.
AB  - Previous studies have suggested the use of the FlexHR method for predicting daily
      energy expenditure in various populations. We investigated the stability of the
      relation between oxygen consumption (VO2) and heart rate (HR) in obese subjects
      undergoing a fitness and weight reduction program. Eleven obese (BMI>30) healthy
      subjects (6 males, 5 females) were recruited from a Wellness program. Subjects
      performed a laboratory calibration procedure between HR and VO2 in resting and
      exercising conditions, before starting the Wellness program (Stage I) and after
      reducing 10% of their initial body weights (BW) within 6 months (Stage II). Mean
      BW, BMI and % body fat were reduced by 13.1+/-4.4 kg, 4.2+/-1.4 kg.m-2 and 6.8+/
      4.1%, respectively, for all parameters (P<0.001). Mean peak VO2 increased from
      31.3+/-7.1 at the beginning to 37.2+/-7.3 mL.kg-1.min-1 at the end of the
      intervention period (P<0.01). The mean flex HR point changed from 96+/-14 to 86+/
      15 beats.min-1 (P<0.05). There were no significant individual differences in the
      HR-VO2 prediction equations derived from the laboratory calibrations in either
      stage. In conclusion, the relationship between HR and VO2 consumption remains
      stable during a time period of weight reduction. The use of the FlexHR method for
      predicting energy expenditure by heart rate monitoring is recommended for
      subjects undergoing a weight-reduction program. It should be taken in account,
      however, that an increase in aerobic capacity, in parallel to changes in body
      weight and composition, might cause a decrease in the flex point.

PMID- 21904288
TI  - Goal orientations and sport motivation, differences between the athletes of
      competitive and non-competitive rhythmic gymnastics.
AB  - AIM: The present study examines the sport motivation and the goal orientations in
      the competitive and non-competitive structure of rhythmic gymnastics.
      Participation of individuals in one or the other structure of the sport differs
      in line with the goals they want to achieve and possibly also with respect to the
      factors that impulse them to take part in one or the other. The purpose of this
      study is to examine how individuals who participate in different structures of
      the sport of rhythmic gymnastics differentiate with regard to the type of
      motivation (intrinsic, extrinsic, amotivation) and goal orientations. METHODS:
      The study involved 98 young female rhythmic gymnastics athletes (aged 14 years
      and up), out of which 40 were athletes of competitive clubs or members of
      national teams, and 58 were athletes of non-competitive clubs. For the evaluation
      of motivation and goal orientations the following tools were used: the Sport
      Motivation Scale (SMS) and the Task and Ego Orientation in Sport Questionnaire
      (TEOSQ). Descriptive and inductive statistical data analysis was conducted.
      RESULTS: The results showed that the athletes of the non-competitive structure
      presented higher levels of introjected regulation (extrinsic motivation),
      amotivation and lower levels of ego orientation (P<0.05). Rhythmic gymnastics
      athletes' (regardless of the structure of the sport) presented high level in task
      orientation while the high levels of task orientation is positively associated
      with high levels of intrinsic motivation regardless of the levels of ego
      orientation. CONCLUSION: The intrinsic motivation of athletes participating in
      rhythmic gymnastics runs at high levels. The amotivation of rhythmic gymnastics
      athletes' is a phenomenon which is also presented in the the non-competitive
      sport structure. It is important that the two different structures of sports be
      determined with accurate criteria.

PMID- 21904289
TI  - Effects of strength and aerobic-based training on functional fitness, mood and
      the relationship between fatness and mood in older adults.
AB  - AIM: Physical independence and positive mood states contribute to successful
      aging. The aim of this study was to analyze the effects of aerobic and strength
      based training programs on functional fitness and mood in older adults, and to
      assess the relationship between adiposity and mood states. METHODS: Seventy eight
      participants (age 65 to 95 year old) were randomly assigned to a control group,
      aerobic training (AT), or strength training group (ST). Functional fitness was
      assessed using dimensions of the Senior Fitness Test battery relating to lower
      and upper body strength and flexibility, velocity, agility and dynamic balance,
      and aerobic endurance. Mood states (depression, tension, fatigue, vigour, anger,
      and confusion) were determined using the POMS-SF questionnaire. Participants were
      evaluated at the baseline and at the end of a 16-week exercise programme.
      RESULTS: Both the ST and AT groups improved their functional fitness following
      the 16 week training. Body Mass Index (BMI) was positively associated with
      tension (r=0.30; P<0.01), fatigue (r=0.31; P<0.01) and confusion (r=0.24;
      P<0.05). At 16-week evaluation, control group reported increased levels of
      confusion, and the ST group reported increases in vigour (P<0.05). CONCLUSION:
      Results support the idea that strength-based training can be as effective as
      aerobic-based training in improving physical skills that contribute to functional
      mobility in later years. Positive associations between increased BMI and mood
      disturbance were also found. Physical training also contributed to some
      improvements in mood.

PMID- 21904290
TI  - Radiological changes and signs of osteoarthritis in the fingers of male
      performance sport climbers.
AB  - AIM: The aim of this study was to investigate the radiological changes and signs
      of osteoarthritis in the fingers of performance sport climbers that felt to be
      from acute mechanical stress placed on the fingers and intense training regime
      over years. METHODS: A total of 31 male sport climbers who were either strong
      rock climbers or former members of the Swiss climbing team, and 67 non-climbers
      participated in the study. Fisher's exact test was used to compare the
      proportions of signs of osteoarthritis between climbers and non-climbers. For the
      evaluation of radiological changes, antero-posterior and lateral radiographs were
      taken of both hands. Distal interphalangeal (DIP) and proximal interphalangeal
      (PIP) joints of the fingers Dig. II-V on the antero-posterior radiographs were
      scored for signs of osteoarthritis using an atlas (Altman) method. Osteophytes at
      the DIP and PIP joints were also evaluated on lateral radiographs and compared to
      the findings on the antero-posterior radiographs. RESULTS: According to the
      Kellgren-Lawrence method, 6 out of 31 climbers had evidence of clear signs of
      osteoarthritis in the fingers, whereas none of the non-climbers developed any
      signs of osteoarthritis (P<=0.001). Twenty-three climbers had definite signs of
      osteophytosis using antero-posterior radiographs compared to 31 climbers using
      lateral radiographs. Lateral radiographs have shown to be more accurate in
      finding, localizing and rating of osteophytes than antero-posterior radiographs.
      CONCLUSION: Male climbers have more signs of osteoarthritis compared to male non
      climbers at similar age. Development of osteophytes seems to be ordinary in every
      climber. Lateral radiographs are more accurate in diagnosing osteophytes in
      climbers than using traditional antero-posterior radiographs.

PMID- 21904291
TI  - Evaluation of energy expenditure in children with cerebral palsy using a multi
      sensor accelerometer.
AB  - AIM: The aim of this paper was to evaluate the validity and reliability of a
      multisensor accelerometer, the Intelligent Device for Energy Expenditure and
      Activity (IDEEA, MiniSun, CA), for measuring energy expenditure in children with
      cerebral palsy (CP). Twenty-one children with CP, age range 4-10 years, with
      varying degrees of impairment, were recruited for the study. In addition, 7
      children with normal development, age range 5.67-8.5 years, were also tested.
      METHODS: Children were connected to a portable metabolic cart (Cosmed, Rome,
      Italy) and to the IDEEA by five sensors. Children were asked to perform a series
      of activities simulating everyday activity, walk on a treadmill for 4 min and
      climb a staircase for 4 min. During all activities oxygen consumption values were
      measured and converted to energy units. Energy expenditure as measured by the
      IDEEA was also recorded. RESULTS: During the simulation of daily activities and
      during walking at a comfortable speed the IDEEA significantly overestimated the
      energy expenditure. However significant and relatively high positive correlations
      (0.70-0.97) were found between the two instruments. Inconsistent results were
      obtained during walking at increased speed. During a step test similar means were
      found by the two instruments for children with normal development and children
      with CP with good correlations between the values measured by the two
      instruments. Energy expenditure measurement in children with CP were found to be
      very reliable, with a correlation of 0.998 for repeated measurements during
      treadmill walking. CONCLUSION: It seems IDEEA, with its present conversion
      equations, is not suitable for exact evaluation of energy expenditure in children
      with CP or in young children with normal development. However, in light of the
      good correlation with the standard method of evaluating energy expenditure and
      the high test-retest reliability of the IDEEA's measurements, It is suggested
      that IDEEA may be a valuable tool for clinical follow-up of children with CP for
      quantitative evaluation of the efficacy of treatment interventions. The
      establishment of population specific conversion equations is expected to
      significantly increase the accuracy of energy expenditure evaluation by the
      IDEEA.

PMID- 21904292
TI  - Markers of bone turnover across a competitive season in female athletes: a
      preliminary investigation.
AB  - AIM: Higher levels of bone formation have been observed in athletes performing
      high impact exercise when compared to non-impact exercisers. This study was
      designed to determine if bone formation and resorption fluctuate across a
      competitive season (4-6 months) in females training at different levels of
      mechanical stress. METHODS: Markers of bone formation (osteocalcin [OC]; bone
      specific alkaline phosphatase [BAP]) and resorption (cross-linked N-telopeptides
      [NTx]) were measured in serum at pre-, mid- and post-season in 33 female athletes
      and controls (19.6+/-1.4 yr). Participants were divided into impact groups of
      high (HIGH, basketball, N.=6), medium (MED, soccer, N.=12), and non (NON,
      swimmers, N.=11), and compared to sedentary controls (CON, N.=4). Bone mineral
      density (BMD) and bone mineral content (BMC) were assessed by DXA in a subset of
      each group. RESULTS: BAP was greater in HIGH and MED (31.82+/-12.21 and 33.09+/
      6.78 U/L) than both NON and CON (23.96+/-5.71 and 16.66+/-2.07 U/L); no
      significant changes over time were noted. Hip BMD was greater in HIGH (1.17+/
      0.14 g*cm-2) than NON and CON (0.98+/-0.09 and 1.02+/-0.04 g*cm-2, respectively),
      while hip BMC was greater in HIGH and MED (41.76+/-3.06 and 38.56 +/- 3.94 g)
      than NON and CON (32.37 +/-3.5 and 30.51 +/- 5.91). CONCLUSION: Women involved in
      HIGH and MED impact activities have higher levels of bone formation throughout a
      season than those involved in non-impact activities which may have long term
      implications for bone health.

PMID- 21904293
TI  - Effect of aerobic exercise on insulin, insulin-like growth factor-1 and insulin
      like growth factor binding protein-3 in overweight and obese postmenopausal
      women.
AB  - AIM: The purpose of presented study was to verify the influence of aerobic
      physical activity program on the serum insulin, insulin-like growth factor-1 (IGF
      1) and insulin-like growth factor binding protein-3 (IGFBP-3) concentrations in
      overweight and obese postmenopausal women. METHODS: Somatic parameters and serum
      concentrations of insulin, IGF-1 and IGFBP-3 were measured in 21 overweight and
      obese women, before and after 8-week cycloergometer physical workout and 16 age
      matched, controls. Age of all studied women ranged from 54 to 78 years. RESULTS:
      The comparative analysis of biochemical indices measured before and after the
      training program showed that the systematic exercise cause the significant
      decrease in insulin (P<0.05) and IGF-1 concentrations (P<0.05). There were no
      differences in these parameters in controls over the studied period. The level of
      IGFBP-3 was not significantly changed in both investigated groups. In women
      participating in the training program the positive correlation (P<0.05) between
      changes in IGF-1 levels (Delta) and changes in insulin concentrations (Delta)
      within two terms of the study were found. The magnitude of changes (Delta) in
      insulin and IGF-1 levels over the study period correlated with their
      concentrations measured before the training program (P<0.01). CONCLUSION: Results
      of the present study indicate that regular aerobic physical activity decreases
      serum insulin and IGF-1 levels in postmenopausal women. The magnitude of insulin
      and IGF-1 concentration changes depend on their initial levels. Changes of IGF-1
      levels are associated with insulin concentration modifications.

PMID- 21904294
TI  - Acute oxidative stress and antioxidant status responses following an American
      football match.
AB  - AIM: Intense physical activity is known to induce oxidative stress. Though
      regular physical training enhances the antioxidant defence system, the effects of
      diminished training periods are unclear. American football is one of the recently
      popular sports in Turkiye and is defined as a mixed activity. The aim of the
      research was to examine some markers of oxidative stress and antioxidant status
      in occasionally competitive American football players following a match, and
      relations with aerobic power and playing position. METHODS: Twenty two male
      players volunteered for the study. To determine oxidative stress and antioxidant
      status from blood samples collected before and immediately following a match,
      plasma malondialdehyde (MDA) and nitric oxide (NO) levels, erythrocyte superoxide
      dismutase (SOD) and glutathione peroxidase (GPx) activities, and total
      antioxidant status (TAS) were assessed, using spectrophotometric methods.
      Wilcoxon's signed rank test was used to determine the match effect, and Mann
      Whitney U test was used to compare playing position and VO2max effects. RESULTS:
      Plasma MDA (P<0.001) and NO (P<0.05) levels increased significantly following the
      match. Antioxidant parameters were unchanged following the match when compared
      with the resting level, except for a VO2max related effect (P<0.05) on TAS.
      CONCLUSION: Collected data revealed that an American football match caused
      excessive production of free radicals and oxidative stress. The training loads
      players underwent were not high enough to cause positive effects on the
      antioxidant status. To enhance training-induced antioxidant status adaptation,
      higher amounts of physical activity may be required.

PMID- 21904295
TI  - Measuring the kinetics of mRNA transcription in single living cells.
AB  - The transcriptional activity of RNA polymerase II (Pol II) is a dynamic process
      and therefore measuring the kinetics of the transcriptional process in vivo is of
      importance. Pol II kinetics have been measured using biochemical or molecular
      methods. In recent years, with the development of new visualization methods, it
      has become possible to follow transcription as it occurs in real time in single
      living cells. Herein we describe how to perform analysis of Pol II elongation
      kinetics on a specific gene in living cells. Using a cell line in which a
      specific gene locus (DNA), its mRNA product, and the final protein product can be
      fluorescently labeled and visualized in vivo, it is possible to detect the actual
      transcription of mRNAs on the gene of interest. The mRNA is fluorescently tagged
      using the MS2 system for tagging mRNAs in vivo, where the 3'UTR of the mRNA
      transcripts contain 24 MS2 stem-loop repeats, which provide highly specific
      binding sites for the YFP-MS2 coat protein that labels the mRNA as it is
      transcribed. To monitor the kinetics of transcription we use the Fluorescence
      Recovery After Photobleaching (FRAP) method. By photobleaching the YFP-MS2-tagged
      nascent transcripts at the site of transcription and then following the recovery
      of this signal over time, we obtain the synthesis rate of the newly made mRNAs.
      In other words, YFP-MS2 fluorescence recovery reflects the generation of new MS2
      stem-loops in the nascent transcripts and their binding by fluorescent free YFP
      MS2 molecules entering from the surrounding nucleoplasm. The FRAP recovery curves
      are then analyzed using mathematical mechanistic models formalized by a series of
      differential equations, in order to retrieve the kinetic time parameters of
      transcription.

PMID- 21904296
TI  - Effect of early breast milk expression on milk volume and timing of lactogenesis
      stage II among mothers of very low birth weight infants: a pilot study.
AB  - OBJECTIVE: The purpose of this randomized pilot study was to collect preliminary
      data regarding the feasibility and effects of early initiation of milk expression
      on the onset of lactogenesis stage II and milk volume in mothers of very low
      birth weight (VLBW) infants. STUDY DESIGN: Twenty women were randomized to
      initiate milk expression within 60 min (group 1) or 1 to 6 h (group 2) following
      delivery. Milk volume and timing of lactogenesis stage II was compared between
      groups using Wilcoxon's rank sum tests. RESULT: Group 1 produced statistically
      significantly more milk than group 2 during the first 7 days (P=0.05) and at week
      3 (P=0.01). Group 1 also demonstrated a significantly earlier lactogenesis stage
      II (P=0.03). CONCLUSION: Initiation of milk expression within 1 h following
      delivery increases milk volume and decreases time to lactogenesis stage II in
      mothers of VLBW infants.

PMID- 21904297
TI  - Biopsychosocial risks of parental care for high-risk neonates: implications for
      evidence-based parental counseling.
AB  - OBJECTIVE: Provide an evidence base for counseling parents of high-risk neonates
      about the biopsychosocial impact of providing long-term care. STUDY DESIGN: A
      review of the effects of long-term care on families of high-risk neonates. Our
      search was limited to 1993-2010. We used the terms 'long-term care,' 'family,'
      'neonate' and 'technology dependence.' Results were organized based on Engel's
      biopsychosocial model. RESULT: Physical-parental caregivers reported more health
      problems, had fewer health-promoting behaviors and lower vitality.Psychological
      parental caregivers had higher rates of post-traumatic stress disorder and
      depressive symptoms, although some improved with time. Siblings reported greater
      stress and depression. Social-parental caregivers achieved fewer years of
      education, higher unemployment and lower incomes. Couples reported greater family
      strain. The effect on divorce was mixed. Siblings reported disruption in their
      academic and social lives. CONCLUSION: Providing long-term care involves
      biopsychosocial risks. Counseling of parents should identify them and advocate
      strategies for prevention.

PMID- 21904299
TI  - The retinoic acid receptor-related orphan nuclear receptor gamma1 (RORgamma1): a
      novel player determinant of insulin sensitivity in morbid obesity.
AB  - The orphan nuclear receptors (ONRs), retinoic acid receptor-related orphan
      receptor gamma-1 (RORgamma1) and peroxisome proliferator-activated receptor gamma
      2 (PPARgamma2), are central mediators controlling adipocyte (AD) differentiation.
      Through their distinct tissue distribution and specific target gene activation,
      ONRs control diverse aspects of fatty acid metabolism and insulin sensitivity.
      Adding further complexity, obesity begets resistance to insulin signals and can
      ultimately result in diabetes. In this study, we investigate whether there are
      differences in the RORgamma1 and PPARgamma2 expression in visceral adipose tissue
      (VAT) and subcutaneous adipose tissue (SAT) from morbid obesity (MO) individuals
      either insulin resistant (high-IR MO) or insulin sensitivity (low-IR MO). Our
      results indicate for the first time in human the RORgamma1 mRNA and protein
      expression levels and activation with coactivator, such as peroxisome
      proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) were
      higher in the VAT from high-IR MO. In contrast, PPARgamma2 expression and
      activation were higher in the VAT from low-IR MO. In this way, we have also found
      a positive association between RORgamma1 mRNA and protein expression with many
      components of metabolic syndrome, with a strong dependence of insulin and
      HOMA(IR) index in VAT, but not in SAT. Our data suggest that RORgamma1 may be
      added to the growing list of nuclear receptors in adipose tissue use to modulate
      the insulin resistance associated to the obesity. Measurement of RORgamma1 and
      PPARgamma2 in adipose tissue might be useful for evaluating the outcomes of
      various clinical interventions for obesity-related diabetes type II.

PMID- 21904301
TI  - Outbreak genomics.

PMID- 21904298
TI  - Fetal sex-related dysregulation in testosterone production and their receptor
      expression in the human placenta with preeclampsia.
AB  - OBJECTIVE: To determine the effects of fetal sex on aromatase and androgen
      receptor (AR) expression in the placenta of normal and preeclamptic pregnancies.
      STUDY DESIGN: Placentae from preeclamptic (five female and six male fetuses) and
      healthy pregnancies (seven female and seven male fetuses) were examined by
      immunofluorescence, western blotting and quantitative reverse transcriptase PCR.
      RESULT: Placental AR levels were significantly higher (P<0.05) in placentae of
      both male and female fetuses compared with their respective sexes in normal
      pregnancies. The placental aromatase levels varied depending on fetal sex. If the
      fetus was female, aromatase levels were substantially higher (P<0.05) in
      preeclamptic than in normal placentae. If the fetus was male, the aromatase
      levels were significantly lower (P<0.05) in preeclamptic than in normal
      placentae. Placental aromatase levels were significantly higher (P<0.05) in male-
      than in female-bearing normal placentae. CONCLUSION: Dysregulation in androgen
      production and signaling in preeclamptic placentae may contribute to placental
      abnormalities, increasing the frequency of maternal-fetal complications
      associated with preeclampsia.

PMID- 21904302
TI  - Myriad decision reassures biotechs but diagnostics still murky.

PMID- 21904303
TI  - GM grass eludes outmoded USDA oversight.

PMID- 21904304
TI  - New models emerge for commercializing university assets.

PMID- 21904306
TI  - BIO marches to Congress with growth package in hand.

PMID- 21904309
TI  - Drugmakers use real-world patient data to calibrate product development.

PMID- 21904312
TI  - Biotech on pace for record year.

PMID- 21904313
TI  - Trends in biotech literature 2009-2010.

PMID- 21904314
TI  - More than insulin.

PMID- 21904315
TI  - Shaping the future of safer innovative drugs in Europe.

PMID- 21904316
TI  - Clarity and claims in variation/mutation databasing.

PMID- 21904318
TI  - Why an abbreviated FDA pathway for biosimilars is overhyped.

PMID- 21904320
TI  - Comprehensive catalog of European biobanks.

PMID- 21904321
TI  - Pharmaceutical patent evaluation and licensing using a stochastic model and Monte
      Carlo simulations.

PMID- 21904323
TI  - Toward safer regenerative medicine.

PMID- 21904324
TI  - Semiconductors charge into sequencing.

PMID- 21904325
TI  - Genome remodeling.

PMID- 21904331
TI  - Verification of systems biology research in the age of collaborative competition.

PMID- 21904332
TI  - Second-quarter biotech job picture.

PMID- 21904334
TI  - Estimating the need for dental sedation. 1. The Indicator of Sedation Need (IOSN)
      - a novel assessment tool.
AB  - While the control of pain and anxiety is fundamental to the practice of
      dentistry, the use of conscious sedation in dentistry is very variable among
      dentists. The need for conscious sedation could be considered by assessing and
      ranking a combination of information on patient anxiety, medical history and the
      complexity of the anticipated clinical treatment. By undertaking this systemtic
      assessment an indication of sedation need may be developed which would act as an
      aide to decision making and, potentially, referral management. Such a tool could
      also be used by commissioners who need to identify patients who need conscious
      sedation for dental treatment in order to plan, commission and deliver
      appropriate sedation services.

PMID- 21904335
TI  - Estimating the need for dental sedation. 2. Using IOSN as a health needs
      assessment tool.
AB  - AIM: This service evaluation assessed the need for sedation in a population of
      dental attenders (n = 607) in the North West of England. METHODS: Using the novel
      IOSN tool, three clinical domains of sedation need were assessed: treatment
      complexity, medical and behavioural indicators and patient reported anxiety using
      the Modified Dental Anxiety Scale. RESULTS: The findings suggest that 5% of the
      population are likely to require a course of treatment under sedation at some
      time. All three clinical domains contributed to the IOSN score and indication of
      treatment need. Females were 3.8 times more likely than males to be placed within
      the high need for sedation group. Factors such as age, deprivation and practice
      location were not associated with the need for sedation. CONCLUSIONS: Primary
      care trusts (PCTs) need health needs assessment data in order to commission
      effectively and in line with World Class Commissioning guidelines. This study
      provides both an indicative figure of need as well as a tool by which individual
      PCTs can undertake local health needs assessment work. Caution should be taken
      with the figure as a total need within a population as the study has only
      included those patients that attended dental practices.

PMID- 21904336
TI  - Disgusted of Tunbridge Wells.

PMID- 21904337
TI  - Outdated misconceptions.

PMID- 21904338
TI  - DLBCL awareness.

PMID- 21904339
TI  - Choumps.

PMID- 21904342
TI  - Hominids shrank molars through cooking.

PMID- 21904343
TI  - 'I've got #toothache'.

PMID- 21904350
TI  - The problem with an epidemiological index for dental erosion.
AB  - This article reviews and discusses the difficulties posed by the application of
      epidemiological indices for the measurement of dental erosion. It covers several
      aspects of index design.

PMID- 21904351
TI  - First report of an acute purulent maxillary sinusitis caused by Pseudomonas
      aeruginosa secondary to dental implant placement in an immunocompetent patient.
AB  - STUDY DESIGN: In this case report, we present maxillary Pseudomonas aeruginosa
      sinusitis in an immunocompetent patient who underwent an autologous bone
      transplant for the insertion of dental implants. RESULTS: The infection was
      eradicated after removal of the dental implants and long-term antibiotic therapy.
      CONCLUSION: Despite the infection resolution, severe complications were observed
      with important legal consequences.

PMID- 21904352
TI  - The diabetic patient and dental treatment: an update.
AB  - This paper has been written to both refresh and update clinicians' knowledge of
      diabetes. Treatment for patients with diabetes continues to develop with the
      majority of Type 1 diabetics now using multiple daily injections and an
      increasing minority using insulin pumps. Blood glucose monitoring and patient
      education programmes have resulted in more patient involvement in controlling
      this condition. Type 2 diabetics have had improvement in care provision through
      the development of shorter acting sulphonylureas and the potential for GLP1
      injections. The impact of diabetes on both oral health and quality of life is
      discussed. Practical suggestions are made regarding the dental treatment of
      diabetic patients using both local anaesthetic and under sedation. Diabetes
      continues to be a fickle master for those affected by this condition. The paper
      is written from the perspective of the 'expert patient'. It is hoped that a
      greater understanding of this chronic condition will improve both access to, and
      safety of, dental care for those patients with diabetes.

PMID- 21904357
TI  - Summary of: estimating the need for dental sedation. 1. The Indicator of Sedation
      Need (IOSN) - a novel assessment tool.
AB  - While the control of pain and anxiety is fundamental to the practice of
      dentistry, the use of conscious sedation in dentistry is very variable among
      dentists. The need for conscious sedation could be considered by assessing and
      ranking a combination of information on patient anxiety, medical history and the
      complexity of the anticipated clinical treatment. By undertaking this systemtic
      assessment an indication of sedation need may be developed which would act as an
      aide to decision making and, potentially, referral management. Such a tool could
      also be used by commissioners who need to identify patients who need conscious
      sedation for dental treatment in order to plan, commission and deliver
      appropriate sedation services.

PMID- 21904358
TI  - Summary of: estimating the need for dental sedation. 2. Using IOSN as a health
      needs assessment tool.
AB  - AIM: This service evaluation assessed the need for sedation in a population of
      dental attenders (n = 607) in the North West of England. METHODS: Using the novel
      IOSN tool, three clinical domains of sedation need were assessed: treatment
      complexity, medical and behavioural indicators and patient reported anxiety using
      the Modified Dental Anxiety Scale. RESULTS: The findings suggest that 5% of the
      population are likely to require a course of treatment under sedation at some
      time. All three clinical domains contributed to the IOSN score and indication of
      treatment need. Females were 3.8 times more likely than males to be placed within
      the high need for sedation group. Factors such as age, deprivation and practice
      location were not associated with the need for sedation. CONCLUSIONS: Primary
      care trusts (PCTs) need health needs assessment data in order to commission
      effectively and in line with World Class Commissioning guidelines. This study
      provides both an indicative figure of need as well as a tool by which individual
      PCTs can undertake local health needs assessment work. Caution should be taken
      with the figure as a total need within a population as the study has only
      included those patients that attended dental practices.

PMID- 21904359
TI  - Policies of dental journals for reporting and monitoring authorship and
      contributorship.
AB  - Authorship contribution is an important issue that has been discussed frequently
      in the medical literature. There are many reported cases of 'guest' authors (who
      sign as authors without meeting authorship criteria) and 'ghost' authors (who are
      credited to get authorship, but for some reason do not sign the article).
      Therefore, clear and transparent policies for reporting
      authorship/contributorship are needed in scientific journals. The objective of
      this survey was to assess the authorship and contributorship policies that are
      made publically available on the homepages of dental journals. The policies of 64
      impact factor-ranked dental journals were assessed with a 6-item checklist based
      on the International Committee of Medical Journal Editors (ICMJE) guidelines for
      authorship/contributorship. Most dental journals partially reported the ICMJE
      guidelines, and therefore the improvement of this reporting is a requirement to
      promote transparency and integrity in dental research. Moreover, dental journals
      should develop strategies to improve author adherence to available guidelines for
      authorship and contributorship.

PMID- 21904378
TI  - The surface molecule signature of primary human acute myeloid leukemia (AML)
      cells is highly associated with NPM1 mutation status.

PMID- 21904377
TI  - Allogeneic transplantation following a reduced-intensity conditioning regimen in
      relapsed/refractory peripheral T-cell lymphomas: long-term remissions and
      response to donor lymphocyte infusions support the role of a graft-versus
      lymphoma effect.
AB  - Rescue chemotherapy or autologous stem cell transplantation (autoSCT) gives
      disappointing results in relapsed peripheral T-cell lymphomas (PTCLs). We have
      retrospectively evaluated the long-term outcome of 52 patients receiving
      allogeneic SCT for relapsed disease. Histologies were PTCL-not-otherwise
      specified (n=23), anaplastic large-cell lymphoma (n=11), angioimmunoblastic T
      cell lymphomas (n=9) and rare subtypes (n=9). Patients were allografted from
      related siblings (n=33, 64%) or alternative donors (n=13 (25%) from unrelated and
      6 (11%) from haploidentical family donors), following reduced-intensity
      conditioning (RIC) regimens including thiotepa, fludarabine and cyclophosphamide.
      Most of the patients had chemosensitive disease (n=39, 75%) and 27 (52%) failed a
      previous autoSCT. At a median follow-up of 67 months, 27 of 52 patients were
      found to be alive (52%) and 25 (48%) were dead (n=19 disease progression, n=6 non
      relapse mortality (NRM)). The cumulative incidence (CI) of NRM was 12% at 5
      years. Extensive chronic graft-versus-host disease increased the risk of NRM (33%
      versus 8%, P=0.04). The CI of relapse was 49% at 5 years, influenced by disease
      status at the time of allografting (P=0.0009) and treatment lines (P=0.007). Five
      year overall survival and progression-free survival (PFS) were 50% (95% CI, 36 -
      63%) and 40% (95% CI, 27 - 53%), respectively. The current PFS was 44% (95% CI,
      30-57%). In all, 8 out of 12 patients (66%) who received donor-lymphocytes
      infusions for disease progression had a response. At multivariable analysis,
      refractory disease and age over 45 years were independent adverse prognostic
      factors. RIC allogeneic SCT is an effective salvage treatment with a better
      outcome for younger patients with chemosensitive disease.

PMID- 21904379
TI  - Impact of arsenic trioxide in the treatment of acute promyelocytic leukemia.
AB  - Arsenic trioxide (ATO) is presently the most active single agent in the treatment
      of acute promyelocytic leukemia (APL). This review provides insights into the
      mode of action and the pharmacological properties of ATO, and summarizes the most
      relevant results of more than 20 treatment studies in relapsed or newly diagnosed
      APL published between 1997 and 2011. ATO acts by targeting multiple pathways in
      APL leading to apoptosis and myeloid differentiation. It induces complete
      remission without myelosuppression and causes only few adverse effects. In
      relapsed APL, ATO-based salvage therapy has been able to induce long-lasting
      remissions and possible cure in 50-81% of patients. In newly diagnosed APL, two
      main strategies are currently pursued. ATO is either included into induction
      therapy with the aim to minimize or eliminate chemotherapy, or it is incorporated
      as an additive into established first-line concepts with all-trans-retinoic acid
      and chemotherapy to reinforce their anti-leukemic efficacy. Recent results
      suggest a high efficacy of ATO in both concepts. In conclusion, experimental
      research and clinical studies have made contributions toward a better
      understanding of the molecular mechanisms induced by ATO in APL cells and have
      established this historic substance as an important candidate for the further
      improvement of APL therapy.

PMID- 21904380
TI  - MRx102, a triptolide derivative, has potent antileukemic activity in vitro and in
      a murine model of AML.
AB  - Triptolide, isolated from the herb Tripterygium wilfordii, has been shown to
      potently induce apoptosis in various malignant cells by inhibiting RNA synthesis
      and nuclear factor-kappaB activity. Previously, we showed that triptolide
      promotes apoptosis in acute myeloid leukemia (AML) cells via the mitochondria
      mediated pathway, in part, by decreasing levels of the anti-apoptotic proteins
      XIAP and Mcl-1. MRx102 is a triptolide derivative, currently in preclinical
      development. Here we show that MRx102 potently promoted apoptosis in AML cell
      lines, with EC(50) values of 14.5+/-0.6 nM and 37.0+/-0.9 nM at 48 h for OCI-AML3
      and MV4-11 cells, respectively. MRx102, at low nanomolar concentrations, also
      induced apoptosis in bulk, CD34(+) progenitor, and more importantly, CD34(+)CD38(
      ) stem/progenitor cells from AML patients, even when they were protected by
      coculture with bone marrow derived mesenchymal stromal cells. MRx102 decreased
      XIAP and Mcl-1 protein levels and inhibited RNA synthesis in OCI-AML3 cells. In
      vivo, MRx102 greatly decreased leukemia burden and increased survival time in non
      obese diabetic/severe combined immunodeficiency mice harboring Ba/F3-ITD cells.
      Collectively, we demonstrated that MRx102 has potent antileukemic activity both
      in vitro and in vivo, has the potential to eliminate AML stem/progenitor cells
      and overcome microenvironmental protection of leukemic cells, and warrants
      clinical investigation.

PMID- 21904381
TI  - NK cells are dysfunctional in human chronic myelogenous leukemia before and on
      imatinib treatment and in BCR-ABL-positive mice.
AB  - Although BCR-ABL+ stem cells in chronic myeloid leukemia (CML) resist elimination
      by targeted pharmacotherapy in most patients, immunological graft-versus-leukemia
      effects can cure the disease. Besides cytotoxic T cells, natural killer (NK)
      cells may have a role in immune control of CML. Here, we explored the
      functionality of NK cells in CML patients and in a transgenic inducible BCR-ABL
      mouse model. Compared with controls, NK-cell proportions among lymphocytes were
      decreased at diagnosis of CML and did not recover during imatinib-induced
      remission for 10-34 months. Functional experiments revealed limited in vitro
      expansion of NK cells from CML patients and a reduced degranulation response to
      K562 target cells both at diagnosis and during imatinib therapy. Consistent with
      the results in human CML, relative numbers of NK1.1+ NK cells were reduced
      following induction of BCR-ABL expression in mice, and the defects persisted
      after BCR-ABL reversion. Moreover, target-induced degranulation by expanded BCR
      ABL+ NK cells was compromised. We conclude that CML is associated with
      quantitative and functional defects within the NK-cell compartment, which is
      reproduced by induced BCR-ABL expression in mice. Further work will aim at
      identifying the mechanisms of NK-cell deficiency in CML and at developing
      strategies to exploit NK cells for immunotherapy.

PMID- 21904382
TI  - How to manage lower-risk myelodysplastic syndromes.
AB  - Patients with lower-risk myelodysplastic syndromes (MDSs), usually defined as
      having an International Prognostic Scoring System score of 1.0 or less, and/or
      <5% myeloblasts, comprise the majority of newly diagnosed and established MDS
      patients and have a survival measured in years. Most will eventually require
      therapy for their disease, usually when MDS-related symptoms or transfusion
      requirements accelerate and outweigh potential drug-related toxicities. The
      decision of when to initiate therapy is far from straightforward. Erythropoiesis
      stimulating agents yield responses in up to 40% of appropriately selected
      patients, while disease-modifying drugs, including lenalidomide, azacitidine,
      decitabine and anti-thymocyte globulin, can evoke responses as high as 67% in
      patient subgroups. Newer therapies hold the promise of activity in patients who
      have failed standard regimens.

PMID- 21904383
TI  - Overexpression of GATA2 predicts an adverse prognosis for patients with acute
      myeloid leukemia and it is associated with distinct molecular abnormalities.

PMID- 21904384
TI  - The NPM1 wild-type OCI-AML2 and the NPM1-mutated OCI-AML3 cell lines carry DNMT3A
      mutations.

PMID- 21904385
TI  - Regulatory T cells and immunodeficiency in mycosis fungoides and Sezary syndrome.
AB  - Cutaneous T-cell lymphoma (CTCL) is the term for diseases characterized by
      primary accumulation of malignant T cells in the skin. Patients with the two
      predominant clinical forms of CTCL called mycosis fungoides (MF) and Sezary
      syndrome (SS) characteristically develop severe immunodeficiency during disease
      progression and consequently patients with advanced disease frequently die of
      infections and not from the tumor burden. For decades, it has been suspected that
      the malignant T cells actively drive the evolving immunodeficiency to avoid
      antitumor immunity, yet, the underlying mechanisms remain unclear. The
      identification of a subset of highly immunosuppressive regulatory T cells (Tregs)
      triggered a variety of studies investigating if MF and SS are malignant
      proliferations of Tregs but seemingly discordant findings have been reported.
      Here, we review the literature to clarify the role of Tregs in MF and SS and
      discuss the potential mechanisms driving the immunodeficiency.

PMID- 21904386
TI  - Trafficking: Tracking immune cells on the lymph node map.

PMID- 21904388
TI  - Inflammasome: NAIPs: pathogen-sensing proteins.

PMID- 21904387
TI  - Inflammatory modulation of HSCs: viewing the HSC as a foundation for the immune
      response.
AB  - Cells of the innate and adaptive immune systems are the progeny of a variety of
      haematopoietic precursors, the most primitive of which is the haematopoietic stem
      cell. Haematopoietic stem cells have been thought of generally as dormant cells
      that are only called upon to divide under extreme conditions, such as bone marrow
      ablation through radiation or chemotherapy. However, recent studies suggest that
      haematopoietic stem cells respond directly and immediately to infections and
      inflammatory signals. In this Review, we summarize the current literature
      regarding the effects of infection on haematopoietic stem cell function and how
      these effects may have a pivotal role in directing the immune response from the
      bone marrow.

PMID- 21904390
TI  - Two novel mutations of the PAX6 gene causing different phenotype in a cohort of
      Chinese patients.
AB  - PURPOSE: Aniridia (AN) is a rare congenital panocular disorder caused by the
      mutations of the paired box homeotic gene 6(PAX6) gene. The PAX6gene is also
      involved in other anterior segment malformations including Peters anomaly. We
      studied the PAX6gene mutations in a cohort of affected individuals with different
      clinical phenotype including AN, coloboma of iris and choroid, or anterior
      segment malformations. PATIENTS AND METHODS: Six unrelated families and 10
      sporadic patients were examined clinically. After informed consent was obtained,
      genomic DNA was extracted from the venous blood of all participants. Mutation
      screening of all exons of the PAX6gene was performed by direct sequencing of PCR
      amplified DNA fragments. Multiplex ligation-dependent probe amplification (MLPA)
      was performed to detect large deletions. RESULTS: By clinical examination, the
      patients and the pedigrees were divided into the following three groups: AN,
      coloboma of iris and choroids, and the anterior segment malformations including
      peters anomaly. Sequencing of the PAX6gene, three intragenic mutations including
      a novel heterozygous splicing-site mutations c.357-3C>G (p.Ser119fsX) were
      identified in the patients of the AN group. A novel missense mutation c.643T>C
      (p.S216P) was detected in the anterior segment malformation group. The mutation
      p.S216P located in the homeodomain region of the PAX6 caused the phenotype of
      Peters anomaly in family A6 with different expressing. Through MLPA analysis, a
      large deletion including the whole PAX6gene and DKFZ p686k1684gene was detected
      in one sporadic patient from the AN group. Neither intragenic mutation nor large
      deletion was identified in the group with coloboma of iris and choroid.
      CONCLUSION: Our findings further confirmed that different kind of mutations might
      cause different ocular phenotype, and clearly clinical phenotype classification
      might increase the mutation detection rate of the PAX6gene.

PMID- 21904389
TI  - New insights into the T cell synapse from single molecule techniques.
AB  - T cell activation depends on extracellular ligation of the T cell receptor (TCR)
      by peptide-MHC complexes in a synapse between the T cell and an antigen
      presenting cell. The process then requires the assembly of signalling complexes
      between the TCR and the adaptor protein linker for activation of T cells (LAT),
      and subsequent filamentous actin (F-actin)-dependent TCR cluster formation.
      Recent progress in each of these areas, made possible by the emergence of new
      techniques, has forced us to rethink our assumptions and consider some radical
      new models. These describe the receptor interaction parameters that control T
      cell responses and the mechanism by which LAT is recruited to the TCR signalling
      machinery. This is an exciting time in T cell biology, and further innovation in
      imaging and genomics is likely to lead to a greater understanding of how T cells
      are activated.

PMID- 21904391
TI  - Anterior segment OCT imaging in opaque grafts with secondary glaucoma following
      tectonic penetrating keratoplasty for perforated corneal ulcers.

PMID- 21904392
TI  - Corneal hysteresis in patients with dry eye.
AB  - PURPOSE: To measure corneal hysteresis and intraocular pressure (IOP) in patients
      with dry eye and to compare with normal subjects. METHODS: This cross-sectional
      study consists of 70 eyes of 40 patients with dry eye (group 1) and 75 eyes of 40
      normal subjects (group 2). Eyes were diagnosed as dry eye or normal according to
      the clinical symptoms, biomicroscopical evaluation, and Schirmer test. Corneal
      hysteresis (CH), corneal resistance factor (CRF), and cornea-compensated
      intraocular pressure (IOPcc) were measured by the Ocular Response Analyser (ORA).
      RESULTS: Mean CH values were 10.56+/-0.25 mm Hg and 10.34+/-0.26 mm Hg, mean CRF
      values were 10.75+/-0.28 mm Hg and 10.70+/-0.28 mm Hg, mean CCT values were 542+/
      3.20 MUm and 543+/-3.89 MUm in group 1 and group 2, respectively. There was no
      statistically significant difference between the groups for these three
      parameters. IOPcc values measured with ORA were 15.73+/-0.36 mm Hg in group 1 and
      16.60+/-0.33 mm Hg in group 2, and there was no statistically significant
      difference between the two groups. CONCLUSIONS: Corneal biomechanical parameters
      such as CH and CRF are not influenced in dry eye. Also statistical difference was
      not found between the two groups according to CCT and IOPcc values.

PMID- 21904393
TI  - Incorporating life expectancy in glaucoma care.
AB  - AIM: To calculate for which combinations of age and perimetric disease stage
      glaucoma patients are unlikely to become visually impaired during their lifetime.
      METHODS: We used residual life expectancy data (life expectancy adjusted for the
      age already reached) as provided by Statistics Netherlands and rates of
      progression as derived from published studies. We calculated the baseline mean
      deviation (MD) for which an individual would reach a MD of -20 dB at the end of
      life as a function of age and rate of progression. For situations in which the
      individual rate of progression is unknown, we used the 90th percentiles of rate
      of progression and residual life expectancy. For situations in which the
      individual rate of progression is known, we used the 95th percentile of the
      residual life expectancy. RESULTS: An easily applicable graphical tool was
      developed that enables an accurate estimate of the probability of becoming
      visually impaired during lifetime, given age, current glaucomatous damage, and-
      if available--the individual rate of progression. CONCLUSIONS: This novel tool
      enables the clinician to incorporate life expectancy in glaucoma care in a well
      founded manner and may serve as a starting point for personalized decision
      making.

PMID- 21904394
TI  - Multispectral retinal image analysis: a novel non-invasive tool for retinal
      imaging.
AB  - PURPOSE: To develop a non-invasive method for quantification of blood and pigment
      distributions across the posterior pole of the fundus from multispectral images
      using a computer-generated reflectance model of the fundus. METHODS: A computer
      model was developed to simulate light interaction with the fundus at different
      wavelengths. The distribution of macular pigment (MP) and retinal haemoglobins in
      the fundus was obtained by comparing the model predictions with multispectral
      image data at each pixel. Fundus images were acquired from 16 healthy subjects
      from various ethnic backgrounds and parametric maps showing the distribution of
      MP and of retinal haemoglobins throughout the posterior pole were computed.
      RESULTS: The relative distributions of MP and retinal haemoglobins in the
      subjects were successfully derived from multispectral images acquired at
      wavelengths 507, 525, 552, 585, 596, and 611 nm, providing certain conditions
      were met and eye movement between exposures was minimal. Recovery of other fundus
      pigments was not feasible and further development of the imaging technique and
      refinement of the software are necessary to understand the full potential of
      multispectral retinal image analysis. CONCLUSION: The distributions of MP and
      retinal haemoglobins obtained in this preliminary investigation are in good
      agreement with published data on normal subjects. The ongoing development of the
      imaging system should allow for absolute parameter values to be computed. A
      further study will investigate subjects with known pathologies to determine the
      effectiveness of the method as a screening and diagnostic tool.

PMID- 21904395
TI  - Treatment of mesothelioma with gene-modified PA1STK cells and ganciclovir: a
      phase I study.
AB  - Mesothelioma is an incurable cancer of the pleura with a life expectancy of less
      than 1 year. On the basis of in vivo efficacy seen with the herpes simplex virus
      type 1 thymidine kinase (HSVtk) suicide gene-modified PA1STK cell line and
      ganciclovir (GCV) in a murine model of mesothelioma, a first in humans, clinical
      trial was designed for this therapeutic concept. The study was a phase I clinical
      trial using direct infusion of escalating doses of HSVtk suicide gene-modified
      PA1STK cells directly into tumor-associated pleural effusions followed by 7 days
      of intravenous GCV infusion. Therapeutic levels of GCV in both serum and pleura
      were achieved within 1 h, and GCV trough levels remained above the therapeutic
      threshold for the duration of GCV treatment. The treatment was well tolerated
      without any Grade 3 or 4 toxicity observed. Significant inductions of both Th1
      and Th2 cytokines up to 20-fold over baseline were observed. No significant
      differences were seen between serum and pleura cytokine profiles, with the
      exception of interleukin-10, which was consistently elevated in the pleura
      specimens. No objective radiographic responses were observed. The data indicate
      significant immunological responses and validate the principal anti-tumor
      mechanisms observed in preclinical models of mesothelioma in a human clinical
      trial.

PMID- 21904396
TI  - Silencing oncogene expression in cervical cancer stem-like cells inhibits their
      cell growth and self-renewal ability.
AB  - Accumulating evidence supports the concept that cancer stem cells (CSCs) are
      responsible for tumor initiation and maintenance. They are also considered as an
      attractive target for advanced cancer therapy. Using a sphere culture method that
      favors the growth of self-renewal cells, we have isolated sphere-forming cells
      (SFCs) from cervical cancer cell lines HeLa and SiHa. HeLa-SFCs were resistant to
      multiple chemotherapeutic drugs and were more tumorigenic, as evidenced by the
      growth of tumors following injection of immunodeficient mice with 1 * 10(4)
      cells, compared with 1 * 10(6) parental HeLa cells required to grow tumors of
      similar size in the same time frame. These cells showed an expression pattern of
      CD44(high)/CD24(low) that resembles the CSC surface biomarker of breast cancer.
      We further demonstrated that HeLa-SFCs expressed a higher level (6.9-fold) of the
      human papillomavirus oncogene E6, compared with that of parental HeLa cells. Gene
      silencing of E6 with a lentiviral-short-hairpin RNA (shRNA) profoundly inhibited
      HeLa-SFC sphere formation and cell growth. The inhibition of cell growth was even
      greater than that for sphere formation after E6 silence, suggesting that the loss
      of self-renewing ability may be more important. We then measured the expression
      of self-renewal genes, transformation growth factor-beta (TGF-beta) and leukemia
      inhibitory factor (LIF), in shRNA-transduced HeLa-SFCs and found that expression
      of all three TGF-beta isoforms was significantly downregulated while LIF remained
      unchanged. Expression of the Ras gene (a downstream component of TGF-beta) was
      also markedly decreased, suggesting that the growth-inhibitory effect could be
      via the TGF-beta pathway. The above data indicate RNA interference-based therapy
      may offer a new approach for CSC-targeted cancer therapy.

PMID- 21904397
TI  - [The association obesity-psychiatric disease. One more need for a
      multidisciplinary approach].

PMID- 21904399
TI  - [Consensus on the legibility criteria of health education leaflets].
AB  - BACKGROUND: To identify the most relevant aspects that guarantee the readability,
      clarity and simplicity of written health education materials. MATERIAL AND
      METHODS: Delphi methodology in order to reach a state of consensus among health
      education experts on criteria of legibility in the design and publication of
      informative material and literature. RESULTS: Seventeen experts reached agreement
      on the principal recommendations for ensuring the legibility of health education
      materials. They were as follows: a) text content and layout: to structure the
      text using a title or subtitle, message explanation and conclusion; b) text
      construction: to use simple and concise sentences, diagrams and examples, and
      graphically highlighting the principal ideas; c) lexical comprehension: to use
      simple words and avoid technical language and abbreviations; d) typography: to
      use an easy-to-read font. CONCLUSIONS: There is a high degree of consensus
      regarding the way health education materials should be drawn up. This list of
      recommendations could be used as an instrument for reviewing and improving the
      design of health education materials. In general, it is recommended to identify
      the users of the leaflets and involve them in the writing and design.

PMID- 21904398
TI  - [Biochemical diagnosis of monomeric hyperprolactinemia].
AB  - BACKGROUND: Prolactin can take several molecular forms of which the most
      biologically active is the monomeric form (PRLm). The presence of macroprolactin
      (MPRL) can give rise to a false diagnosis of hyperprolactinemia due to
      interference in the measuring procedure. The aim was to develop a protocol that
      enables diagnosis of monomeric hyperprolactinemia, which should also be
      complementary to the procedure for detecting MPRL. MATERIAL AND METHODS: The
      reference population for PRLm was made up of 122 healthy women and 140 healthy
      men, from whom blood was extracted for PRL quantification. Additionally, 49
      hyperprolactinemic serums (33 women and 16 men) were collected. PRL was
      quantified in all the samples in an Immulite 2000. The detection of MPRL and PRLm
      was carried out following precipitation with polyetylenglicol (PEG). The result
      was confirmed by gelatin filtration chromatography. The reference values were
      obtained following the indications of the Expert Panel of the IFCC. RESULTS: The
      PRLm reference values were 3,4 - 26,6 ug/L and 4,6 - 16,4 ug/L in women and men,
      respectively. In 57% of the 49 hyperprolactinemic patients the concentration of
      PRLm following PEG fell outside the previously obtained reference interval,
      confirming the presence of monomeric hyperprolactinemia. CONCLUSIONS: A protocol
      for quantifying PRLm has been developed and implemented. Obtaining PRLm reference
      values makes it possible to diagnose monomeric or active hyperprolactinemia in a
      complementary form to the identification of MPRL.

PMID- 21904400
TI  - [Preoperative staging MRI for rectal cancer and pathologic correlation].
AB  - BACKGROUND: Our aim is to asses the accuracy of MRI for preoperative rectal
      cancer staging and to establish a histopathologic correlation. METHODS AND
      MATERIALS: A retrospective analysis was performed on 120 patients aged between 43
      and 87 with histologically proven rectal cancer who underwent MRI for
      preoperative staging in our hospital between 2005 and 2010. Patients were
      categorized according to the TNM classification. RESULTS: Eighty of 120 patients
      underwent adjuvant chemoradiotheraphy because they had advanced disease (T3-T4),
      lymph node involvement (N1-N2) or resectable metastases. With 40 patients who
      didn't undergo neoadjuvant therapy we performed a correlation between MRI and
      histopathological findings with a diagnostic accuracy in predicting T stage of
      72%, N stage of 60% and distance to the mesorectal fascia of 87,5%. CONCLUSION:
      Pelvic MRI is a useful technique for locoregional staging of rectal cancer with a
      good radiopathologic correlation although the identification of nodal disease is
      still a diagnostic problem.

PMID- 21904401
TI  - [Glenohumeral osteometry-scapulometry in anterior shoulder instabilities. Study
      of one of the static stabilizers through computer tomography].
AB  - We have carried out a scapulometric study, using CT-scan, of 98 shoulders: 36
      with recurrent anterior shoulder dislocation (RAD), 37 stable contralateral
      shoulders (CSS) and 25 normal shoulders (NS). Six parameters were evaluated:
      Horizontal and Vertical glenohumeral index, glenoid tilt, anteversion angle of
      the scapula, glenoid angle and humeral retroversion. We found statistically
      significant differences between the RAD and CSS groups in the horizontal
      glenohumeral index. Both the RAD and CSS groups showed significant differences in
      comparison with the NS group in the horizontal glenohumeral index, glenoid tilt
      and anteversion angle of the scapula. An imbalance of the head-glenoid size and
      the anterior glenoid tilt are the anatomical factors which favour instability.
      The determination of these three parameters has great value when assessing
      patients with anterior shoulder instability. Our results confirm that although
      the aetiology of anterior glenohumeral instability is multifactorial, there is an
      anatomical congenital predisposition which favours instability and this
      predisposition affects (to a lesser extent) the stable contralateral side,
      confirming the role of subtle congenital dysplasic theory. In addition the
      following were revealed as relevant parameters in the study of anterior
      instability: the horizontal glenohumeral index, glenoid tilt and angle of
      anteversion of the scapula; while the value of the humeral retroversion is under
      discussion.

PMID- 21904402
TI  - [Impact of universal vaccination against chicken pox in Navarre, 2006-2010].
AB  - BACKGROUND: In 2007 universal vaccination against chicken pox was introduced in
      the vaccine calendar of Navarre. The aim of this study is to evaluate the impact
      of this measure on the incidence of chicken pox in both the vaccinated cohorts
      (direct effect) and in the unvaccinated cohorts (indirect effect). MATERIAL AND
      METHODS: Chicken pox is a disease of individualized compulsory notification. We
      analyzed the annual incidence by age groups between 2006 and 2010. Hospital
      admittances with chicken pox or complicated chicken pox as the principal
      diagnosis were taken from the minimum basic data set on hospital discharges for
      the years 2006 to 2009. RESULTS: The incidence of chicken pox has fallen by
      93.0%, from 8.04 cases per 1,000 inhabitants in 2006 to 0.56 per 1,000
      inhabitants in 2010 (p<0,0001). In children from 1 to 6 years (vaccinated
      cohorts), the incidence of chicken pox has fallen by 96.3%. In the cohorts
      vaccinated at 10 and 14 years, a fall of 93.6% can also be observed in children
      from 10 to 14 years, and of 85.0% in those of 15 to 19 years. In the unvaccinated
      age groups we can observe falls of 88.2% in children under one year, of 73.3% in
      those of 7 to 9 years, and of 84.6% in people over 20 years. In 2006 there were
      25 hospital admissions due to chicken pox in Navarre and in 2009 this figure fell
      to 7. The rate of admissions fell by 71%. CONCLUSION: The introduction of
      universal chicken pox vaccination in Navarre has resulted in a rapid and very
      steep reduction of the incidence of chicken pox in both vaccinated and
      unvaccinated people.

PMID- 21904403
TI  - [Factors associated with unusually long stays in heart failure hospitalizations
      in Spain].
AB  - BACKGROUND: Heart failure is a process of high prevalence that causes repeated
      hospital admissions with increased health care costs. The aim of this article is
      to describe and characterize the cases with long stays due to this syndrome,
      identifying associated factors wherever possible. METHODS: An historical cohort
      of all the episodes of people over 45 years with a diagnosis of heart failure
      admitted in the Spanish Public Health System in the period 1997-2007. SOURCE:
      808,229 episodes classified as Diagnosis Related Groups 127 and 544 according to
      the Minimum Basic Data provided by the Institute for Health Information. We
      assessed sociodemographic variables (age, gender, region), clinical variables
      (comorbidities, complications, type of admission and discharge) and management
      variables (length of stay, type of hospital readmissions). An abnormally
      prolonged stay (APS) was defined as one exceeding the 90th percentile (14 and 16
      days, respectively); we built a logistic regression model to assess their
      possible associated factors. RESULTS: Eleven point four percent (11.4%) presented
      abnormally prolonged stays, showing lower mean age and increased number of
      diagnoses and procedures, readmissions and mortality than the non-abnormally
      prolonged stay group. Anemia, kidney failure, pulmonary embolism or stroke as
      well as readmission and scheduled admission were associated with increased
      likelihood of APS. CONCLUSION: It is possible to define a comorbidities and
      sociodemographic profile to assess the likelihood of a prolonged hospital stay,
      but given the nature of administrative database the model's discriminative
      ability is quite discreet.

PMID- 21904404
TI  - [Molecular subtypes of breast cancer: prognostic implications and clinical and
      immunohistochemical characteristics].
AB  - BACKGROUND: Breast carcinomas are a heterogeneous group of tumours, in both their
      clinical behavior and their prognosis. The aim of this article is to classify
      breast carcinomas according to molecular subtypes by means of immunohistochemical
      markers and to analyse the clinicopathological and immunohistochemical
      characteristics and the patterns of survival and relapse of the different
      subtypes. METHODS: Two hundred and seventy-two patients diagnosed with breast
      cancer were classified into five subtypes: breast carcinomas of the basal type,
      HER2 type, luminal A type, luminal B type and normal. RESULTS: The most frequent
      breast carcinomas were: luminal A type carcinomas (62.5%), luminal B type
      carcinomas (18%), HER2 type carcinomas (9.9%), basal type carcinomas (8.4%) and
      normal phenotype carcinomas (1.4%). Significantly and with greater frequency, the
      luminal type breast carcinomas proved to be well differentiated tumours, of small
      tumoral size, with negative axillary ganglions, at an early stage at the time of
      diagnosis, with high levels of BCL-2 and a low Ki-67 proliferation index. On the
      contrary, the basal type and HER2 carcinomas presented larger tumours, poorly
      differentiated, greater ganglionar involvement and more advanced stages at the
      time of diagnosis. They expressed high Ki-67 proliferation indexes with greater
      frequency and were the subtypes that showed a worse prognosis on global survival
      and progression-free survival curves. CONCLUSION: Breast cancer classification
      based on immunohistochemical (IHC) parameters makes a better prognostic
      definition possible. Both the basal type and the HER2 type breast carcinomas
      present more unfavourable histopathological and IHC characteristics, as well as a
      worse survival and less relapse time, while the luminal type breast carcinomas
      show more benign characteristics and a better prognosis.

PMID- 21904405
TI  - [Facilitators in the implantation of telemedicine services. Perspective of
      professionals involved in its design and implementation].
AB  - BACKGROUND: Given the difficulties encountered by Telemedicine for final
      incorporation into clinical practice and given the lack of scientific evidence
      regarding the most appropriate implementation strategies, it is necessary to
      collect and disseminate lessons gained from experience in its introduction and
      diffusion in our health system. The aim of this study is to identify the
      facilitators perceived by professionals who actively participate in the design
      and implementation of telemedicine projects in the health care system. METHODS:
      Qualitative study of data from semi-structured interviews with 17 key informants
      belonging to different Catalan health organizations. RESULTS: The identified
      facilitators are grouped in four broad areas: a TM service that meets a need
      clearly perceived by practitioners; a core leadership with a clinical profile,
      managing an open, participatory and flexible model that takes into account the
      needs of professionals; the ability to establish partnerships with different
      stakeholders beyond the customer-supplier relationship; and the inclusion in the
      initial design of a strategy for sustainability and normalization. CONCLUSIONS:
      Understanding the facilitators and barriers that appear in the process of
      implementing TM experiences in health care organizations becomes an item of high
      value for its final introduction. An approach combining the evidence on clinical
      effectiveness and cost-benefit with lessons learned about the dynamics of
      implementation and normalization will allow for a holistic understanding of the
      adoption of the TM and provide guidance for improving its organizational
      management.

PMID- 21904406
TI  - [The role of the DOG1 antibody in the diagnosis of gastrointestinal stromal
      tumours - GIST].
AB  - Gatrointestinal stromal tumours (GIST) harbour oncogenic mutations in tyrosin
      kynases receptors (RTKs) including KIT and PDGFRA. The inhibition of this
      activity has been regarded as the primary target for the treatment of these
      patients. Diagnosis of GIST relies on c-KIT inmunoreactivity; however there is a
      4-15% of GISTs that are C-KIT negative which may lead to underdiagnosis of GISTs
      and possible withholding of therapy. The novel gene DOG1 has been found
      overexpressed in GISTs and has potential as a diagnostic marker for GISTs showing
      even more sensitivity (Se) and specificity (Sp) than c-KIT for the diagnosis of
      these tumors. In this study we compared the (Se) and (Sp) of DOG1 in typical and
      atypical GISTs (c-KIT positive or negative) with c-KIT and other mesenchymal
      neoplasms in the differential diagnosis of GISTs We examined 40 GIST (39 showed
      inmunoreactivity for c-KIT and one was c-KIT negative) and another seven fusiform
      tumors. An inmunohistochemical panel was performed with c-KIT, CD34, smooth
      muscle actin, DOG1 and S100 antibodies on both types of neoplasms. The overall Se
      and Sp of DOG1 and KIT in GISTs were nearly identical: 100 and 97,5%. Negativity
      for DOG1 was observed in all fusiform mesenchymal neoplasms. DOG1 is highly
      expressed in GIST and its expression seems quite specific for these tumours when
      the differential diagnosis includes another mesenchymal neoplasms. DOG1 should be
      added to the diagnostic panel evaluating GISTs.

PMID- 21904407
TI  - [Psychopathological comorbidity of obesity].
AB  - Obesity is one of the most important health problems in the early twenty-first
      century as it affects millions of people around the world and remains a major
      cause of mortality. At present there is no clear link between obesity and
      psychopathology, and whether the possible psychological disorders are a cause or
      a consequence of obesity has not yet been clarified either. This paper reviews
      some recent contributions (2007-2010) related to the comorbidity between
      psychopathology and obesity. It can be concluded from this analysis that certain
      psychological disorders seem to be more common in obese people, such as
      depression, anxiety, substance abuse, etc., although the direction of the
      explanatory relation is not clear; moreover, the opposite result has also been
      found. The evidence of likely comorbid psychopathology means that the
      practitioner must consider its assessment in obesity cases, and include a plan
      for a psychiatric and/or psychological therapeutic intervention.

PMID- 21904408
TI  - [Emergent drugs (I): smart drugs].
AB  - In recent years, a series of new drugs, known as smart drugs or legal highs, have
      gaining in popularity. They are easily obtainable through online shops. This is
      happening amongst younger segments of the population and is associated with
      recreational consumption, at weekends. In general, they are synthetic derivatives
      of natural products. There has been hardly any clinical research into them and
      they are not detectable in hospital laboratories. Three of these products, BZP (1
      benzylpiperazine), mefedrone (4-methylmethcathinone) and Spice are probably the
      most widely used in Europe. The first two are consumed as an alternative to
      ecstasy and cocaine and are characterized by their producing a clinical profile
      of a sympathetic mimetic type; on occasion, they have serious consequences, with
      convulsions and even death. Spice (a mixture of herbs with synthetic cannabinoids
      such as JWH-018, JWH-073 and CP 47497-C8) is giving rise to profiles of
      dependence and schizophrenia. Although the emergent drugs have an aura of safety,
      there is an increasing amount of experience on their secondary effects.

PMID- 21904409
TI  - [Multidisciplinary management of ovarian epithelial cancer. Radiological
      diagnosis].
AB  - In the context of a multidisciplinary approach for the diagnosis and treatment of
      ovarian cancer, the contribution of radiology includes the following four
      fundamental points: identification of the lesion, its characterization, study of
      its extension and evaluation of its evolution. This article describes the
      findings and key diagnostic elements in MDCT (Multidetector Computed Tomography)
      and MR (Magnetic Resonance), the contribution and indication of other
      technologies like PET (Positron Emission Tomography), and outlines the emergent
      techniques based on functional image analysis (dynamic contrast-enhanced MRI
      studies and MRI diffusion studies).

PMID- 21904410
TI  - Cuboid-navicular tarsal coalition in an athlete.

PMID- 21904411
TI  - [Influenza A. Act two. Suitability of request for PCR for Influenza A (H1N1) in
      an emergency service department].

PMID- 21904412
TI  - [Right aortic arch, Kommerell's diverticulum and aberrant left subclavian
      artery].
AB  - The right aberrant subclavian artery or "arteria lusoria" is the most common
      anatomical variant of the embryonic development of the aorta and its branches,
      with a presence in 0.5-2% of the population. Less frequently, a right aortic arch
      with aberrant left subclavian artery may be present. These anatomical variations
      should be included in the differential diagnosis of superior mediastinal widening
      seen on chest radiographs. In this report, we present a right aortic arch with
      left aberrant subclavian artery dilated at its origin (Kommerell's diverticulum)
      as a cause of superior mediastinal widening detected incidentally on a chest
      radiograph.

PMID- 21904413
TI  - Nodular glomerulosclerosis in a non-diabetic hypertensive smoker with
      dyslipidemia.
AB  - Nodular glomerulosclerosis may be idiopathic or develop associated with diabetes
      mellitus, membranoprolipherative glomerulonephritis, light or heavy chain
      deposits, amyloidosis, fibrillary or immunotactoide disease, and Takayasu's
      arteritis. Histological features of idiopathic nodular glomerulosclerosis are
      similar to the Kimmelstiel-Wilson changes. Recent evidence points to the role of
      hyperglycemia, hyperlipidemia, hypertension and smoking in the mechanisms of this
      uncommon condition. The case study of a 65-year-old male presenting recent
      arterial hypertension and nodular non-diabetic glomerulosclerosis is described,
      and the possible role of heavy smoking in the pathogenesis of this condition is
      emphasized.

PMID- 21904414
TI  - [Complete response in a patient with a metastatic cutaneous melanoma].
AB  - BACKGROUND: The management of patients with disseminated disease is a difficult
      problem. There is currently no consensus on the standard first-line treatment for
      metastatic melanoma. We present a case because of his exceptional evolution.
      RESULTS: A 43 year old male diagnosed in 1999 with malignant melanoma stage IIA.
      In May 2000 hepatic and splenic metastases were detected. He received 6 cycles of
      biochemotherapy (cisplatin and DTIC, plus interleukin-2 and interferon-alpha) and
      another 6 cycles with single immunotherapy (interleukin-2 and interferon-alpha).
      Today, the patient is still alive and without evidence of disease. CONCLUSION:
      Metastatic cutaneous melanoma, sometimes presents an unusual, favourable
      evolution. In the near future, the methods of detection of molecular markers are
      expected to identify factors involved in this type of response. Furthermore, new
      targeted therapies may become essential to maintain this positive trend.

PMID- 21904415
TI  - [Bilateral posterior scleritis].
AB  - Posterior scleritis is an inflammatory process of the posterior part of the
      sclera. Its prevalence is very low and its diagnosis can be complicated due to
      the absence of external ocular signs. It is more frequent in women. In young
      patients it does not usually have other associated pathologies, but in those over
      55 years nearly one-third of the cases have a relation with some systemic
      disease, above all rheumatoid arthritis. The diagnosis of this pathology can
      require a multidisciplinary approach and the collaboration of ophthalmologists
      with neurologists, internists or rheumatologists. This article describes a case
      of idiopathic bilateral posterior scleritis.

PMID- 21904416
TI  - [The use of SWI-MRI to differentiate between seizures and transient ischemic
      attacks in a patient with cerebral amyloid angiopathy].
AB  - BACKGROUND: Cerebral amyloid angiopathy (CAA) is characterized by the deposit of
      beta-amyloid on the walls of small and medium-sized arteries of the cerebral
      cortex and leptomeninges causing cerebral bleeding. Clinical presentations may
      include transient neurological events for which differential diagnosis can be
      difficult. CASE REPORT: We report a subject with a medical history of a recent
      stroke who presented somesthetic seizures mimicking transient ischemic attacks
      owing to CAA microbleeding. Antiplatelet treatment was reduced and after
      lamotrigine was commenced the episodes disappeared. Susceptibility-weighted
      magnetic resonance imaging was very helpful for diagnosis (SWI-MRI). CONCLUSIONS:
      CAA microbleeding can be manifested in the form of seizures mimicking focal
      transient sensitive neurological deficits that can be erroneously attributed to
      cerebral ischemia. The present case report suggests that, despite the presence of
      a past medical history of strokes, neurologists should consider CAA microbleeding
      as a possible cause of pseudo-transient ischemic attacks. High-resolution
      neuroimaging including SWI-MRI imaging can be helpful in identifying cortical
      microbleedings. In this way, the start or increase of antiplatelet treatment can
      be avoided, and the risk of potentially fatal complications minimized.

PMID- 21904417
TI  - Transannular Anti-Michael Addition: Formation of 4H-Pyrazolo[5,1-c]thiazines.
AB  - The reaction of 2-(diphenylmethylene)thietan-3-one (2) with 1,2,4,5-tetrazines
      (3a-c) in KOH/MeOH/THF gives 4H-pyrazolo[5,1-c]thiazines (7a-c). This no vel
      condensation reaction proceeds via the intermediacy of an 8-(diphenylmethylene)
      2H-1,4,5-thiadiazocin-7(8H)-one (5), which undergoes a multi-step rearrangement
      including a rare anti-Michael addition.

PMID- 21904418
TI  - Rejoinder.

PMID- 21904419
TI  - A Descriptive Study of Home Modifications for People with Dementia and Barriers
      to Implementation.
AB  - This study describes home environmental features, safety issues, and health
      related modifications in a community dwelling sample of 82 elderly people with
      dementia. Main barriers to the accessibility of the homes were steps, both inside
      and outside the house. The majority of the caregivers had made home
      modifications, which pertained mainly to physical limitations. Home modifications
      to support cognitive deficits were made to a lesser extent. The main barrier to
      the implementation of home modifications to accommodate the care recipient's
      memory loss was skepticism about their usefulness. Regarding the removal of
      physical barriers, financial constraints were most frequently mentioned.

PMID- 21904420
TI  - The Neuropathology of Developmental Dysphasia: Behavioral, Morphological, and
      Physiological Evidence for a Pervasive Temporal Processing Disorder.
AB  - Over the past twenty years, Tallal and colleagues have directed their research
      toward defining the neuropathological mechanisms responsible for developmental
      dysphasia. We have hypothesized that higher level auditory processing
      dysfunction, which has previously been associated with developmental dysphasia,
      may result from more basic temporal processing deficits which interfere with the
      resolution of rapidly presented, brief duration stimuli. This temporal processing
      deficit interferes with adequate perception of specific verbal stimuli which
      require resolution of brief duration formant transitions, resulting in disordered
      language development. The temporal processing deficit occurs across multiple
      sensory modalities, and also affects rapid and sequential motor production
      skills. Despite relatively normal clinical neuroradiological examinations, in
      vivo morphological analysis, utilizing magnetic resonance imaging techniques for
      quantitative volumetric measurements of specific brain structures, has identified
      abnormalities in superior parietal, prefrontal, and temporal cortices, as well as
      diencephalic and caudate nuclei. Abnormalities in structures which are involved
      in multimodal processing and sensory motor integration is consistent with the
      behavioral profile of developmental dysphasia. Two alternative hypotheses
      regarding the neurophysiological basis of the multimodal temporal processing
      disorder include: dysfunction in specifc cellular systems which subserve rapid,
      transient processing; and abnormal gating of sensory relay by intralaminar and
      reticular thalamic nuclei.

PMID- 21904421
TI  - Catalytic Addition of Simple Alkenes to Carbonyl Compounds Using Group 10 Metals.
AB  - Recent advances using nickel complexes in the activation of unactivated
      monosubstituted olefins for catalytic intermolecular carbon-carbon bond-forming
      reactions with carbonyl compounds, such as simple aldehydes, isocyanates, and
      conjugated aldehydes and ketones, are discussed. In these reactions, the olefins
      function as vinyl- and allylmetal equivalents, providing a new strategy for
      organic synthesis. Current limitations and the outlook for this new strategy are
      also discussed.

PMID- 21904422
TI  - Homology modeling and consensus protein disorder prediction of human filamin.
AB  - Filamins are dimeric actin-binding proteins participating in the organization of
      the actin-based cytoskeleton. Their modular domain organization is made up of an
      N-terminal actin-binding domain composed of two CH domains followed by flexible
      rod regions that consist of 24 Ig-like domains. Homology modeling was used to
      model human filamin using Modeller 9v5. The resulting model assessed by Verify 3D
      and PROCHECK showed that the final model is reliable. The conformational disorder
      prediction of human filamin residues were also mapped on the validated structure
      of human filamin. Prediction of protein disorder in filamin structures will help
      structural biologists to find suitable targets to be analyzed and for
      understanding protein function.

PMID- 21904423
TI  - Identification of Escherichia coli through analysis of 16S rRNA and 16S-23S rRNA
      internal transcribed spacer region sequences.
AB  - A bacterial strain, designated BzDS03 was isolated from water sample, collected
      from Dal Lake Srinagar. The strain was characterized by using 16S ribosomal RNA
      gene and 16S-23S rRNA internal transcribed spacer region sequences. Phylogenetic
      analysis showed that 16S rRNA sequence of the isolate formed a monophyletic clade
      with genera Escherichia. The closest phylogenetic relative was Escherichia coli
      with 99% 16S rRNA gene sequence similarity. The result of Ribosomal database
      project's classifier tool revealed that the strain BzDS03 belongs to genera
      Escherichia.16S rRNA sequence of isolate was deposited in GenBank with accession
      number FJ961336. Further analysis of 16S-23S rRNA sequence of isolate confirms
      that the identified strain BzDS03 be assigned as the type strain of Escherichia
      coli with 98% 16S-23S rRNA sequence similarity. The GenBank accession number
      allotted for 16S-23S rRNA intergenic spacer sequence of isolate is FJ961337.

PMID- 21904424
TI  - Selection of herbal therapeutics against deltatoxin mediated Clostridial
      infections.
AB  - Clostridium perfringens (a versatile pathogenic bacterium) secretes enterotoxins
      (the deltatoxin, virulent factor) and causes food borne gastroenteritis and
      gasgangrene. The organism was isolated and characterized from improperly cooked
      meat and poultry samples. The isolated organism showed multiple drug resistance
      indicating that the treatment is challenging. Hence, there is need for improved
      therapeutic agents. The rational design of improved therapeutics requires the
      crystal structure for the toxin. However, the structure for the toxin is not yet
      available in its native form. Thus, we modeled the toxin structure using alpha-
      hemolysin of Staphylococcus aureus (PDB: 3M4D chain A) as template. The docking
      of the toxin with the herbal extract curcumin (1,7-bis(4-hydroxy-3-
      methoxyphenyl)hepta-1,6-diene-3,5-dione) showed a binding energy of -8.6
      Kcal/mol, in comparison to the known antibiotic Linezolid with binding energy of 
      6.1 Kcal/mol. This data finds application in the design and development of novel
      compounds against the deltatoxin from Clostridium perfringens.

PMID- 21904425
TI  - SSPred: A prediction server based on SVM for the identification and
      classification of proteins involved in bacterial secretion systems.
AB  - Protein secretion systems used by almost all bacteria are highly significant for
      the normal existence and interaction of bacteria with their host. The
      accumulation of genome sequence data in past few years has provided great
      insights into the distribution and function of these secretion systems. In this
      study, a support vector machine (SVM)- based method, SSPred was developed for the
      automated functional annotation of proteins involved in secretion systems further
      classifying them into five major sub-types (Type-I, Type-II, Type-III, Type-IV
      and Sec systems). The dataset used in this study for training and testing was
      obtained from KEGG and SwissProt database and was curated in order to avoid
      redundancy. To overcome the problem of imbalance in positive and negative
      dataset, an ensemble of SVM modules, each trained on a balanced subset of the
      training data were used. Firstly, protein sequence features like amino-acid
      composition (AAC), dipeptide composition (DPC) and physico-chemical composition
      (PCC) were used to develop the SVM-based modules that achieved an average
      accuracy of 84%, 85.17% and 82.59%, respectively. Secondly, a hybrid module
      (hybrid-I) integrating all the previously used features was developed that
      achieved an average accuracy of 86.12%. Another hybrid module (hybrid-II)
      developed using evolutionary information of a protein sequence extracted from
      position-specific scoring matrix and amino-acid composition achieved a maximum
      average accuracy of 89.73%. On unbiased evaluation using an independent data set,
      SSPred showed good prediction performance in identification and classification of
      secretion systems. SSPred is a freely available World Wide Web server at
      http//www.bioinformatics.org/sspred.

PMID- 21904426
TI  - PDBToSDF: Create ligand structure files from PDB file.
AB  - Protein Data Bank (PDB) file contains atomic data for protein and ligand in
      protein-ligand complexes. Structure data file (SDF) contains data for atoms,
      bonds, connectivity and coordinates of molecule for ligands. We describe PDBToSDF
      as a tool to separate the ligand data from pdb file for the calculation of ligand
      properties like molecular weight, number of hydrogen bond acceptors, hydrogen
      bond receptors easily.

PMID- 21904427
TI  - RegStatGel: proteomic software for identifying differentially expressed proteins
      based on 2D gel images.
AB  - Image analysis of two-dimensional gel electrophoresis is a key step in proteomic
      workflow for identifying proteins that change under different experimental
      conditions. Since there are usually large amount of proteins and variations shown
      in the gel images, the use of software for analysis of 2D gel images is
      inevitable. We developed open-source software with graphical user interface for
      differential analysis of 2D gel images. The user-friendly software, RegStatGel,
      contains fully automated as well as interactive procedures. It was developed and
      has been tested under Matlab 7.01. AVAILABILITY: The database is available for
      free at http://www.mediafire.com/FengLi/2DGelsoftware.

PMID- 21904428
TI  - A web accessible resource for investigating cassava phenomics and genomics
      information: BIOGEN BASE.
AB  - The goal of our research is to establish a unique portal to bring out the
      potential outcome of the research in the Casssava crop. The Biogen base for
      cassava clearly brings out the variations of different traits of the germplasms,
      maintained at the Tapioca and Castor Research Station, Tamil Nadu Agricultural
      University. Phenotypic and genotypic variations of the accessions are clearly
      depicted, for the users to browse and interpret the variations using the
      microsatellite markers. Database (BIOGEN BASE - CASSAVA) is designed using PHP
      and MySQL and is equipped with extensive search options. It is more user-friendly
      and made publicly available, to improve the research and development of cassava
      by making a wealth of genetics and genomics data available through open, common,
      and worldwide forum for all individuals interested in the field. AVAILABILITY:
      The database is available for free at
      http://www.tnaugenomics.com/biogenbase/casava.php.

PMID- 21904429
TI  - Mycobacteriophage genome database.
AB  - Mycobacteriophage genome database (MGDB) is an exclusive repository of the 64
      completely sequenced mycobacteriophages with annotated information. It is a
      comprehensive compilation of the various gene parameters captured from several
      databases pooled together to empower mycobacteriophage researchers. The MGDB
      (Version No.1.0) comprises of 6086 genes from 64 mycobacteriophages classified
      into 72 families based on ACLAME database. Manual curation was aided by
      information available from public databases which was enriched further by
      analysis. Its web interface allows browsing as well as querying the
      classification. The main objective is to collect and organize the complexity
      inherent to mycobacteriophage protein classification in a rational way. The other
      objective is to browse the existing and new genomes and describe their functional
      annotation. AVAILABILITY: The database is available for free at
      http://mpgdb.ibioinformatics.org/mpgdb.php.

PMID- 21904430
TI  - Insights from the molecular docking of withanolide derivatives to the target
      protein PknG from Mycobacterium tuberculosis.
AB  - A crucial virulence factor for intracellular Mycobacterium tuberculosis survival
      is Protein kinase G (PknG), a eukaryotic-like serinethreonine protein kinase
      expressed by pathogenic mycobacteria that blocks the intracellular degradation of
      mycobacteria in lysosomes. Inhibition of PknG results in mycobacterial transfer
      to lysosomes. Withania somnifera, a reputed herb in ayurvedic medicine, comprises
      a large number of steroidal lactones known as withanolides which show various
      pharmacological activities. We describe the docking of 26 withanferin and 14
      withanolides from Withania somnifera into the three dimensional structure of PknG
      of M. tuberculosis using GLIDE. The inhibitor binding positions and affinity were
      evaluated using scoring functions- Glidescore. The withanolide E, F and D and
      Withaferin - diacetate 2 phenoxy ethyl carbonate were identified as potential
      inhibitors of PknG. The available drug molecules and the ligand AX20017 showed
      hydrogen bond interaction with the aminoacid residues Glu233 and Val235. In
      addition to Val235 the other amino acids, Gly237, Gln238 and Ser239 are important
      for withanolide inhibitor recognition via hydrogen bonding mechanisms.

PMID- 21904431
TI  - Functional co-evolutionary study of glucosamine-6-phosphate synthase in mycoses
      causing fungi.
AB  - Invasive fungal opportunistic infections or mycoses have been on the rise with
      increase in the number of immuno-compromised patients accounting for associated
      high morbidity and mortality rates. The antifungal drugs are not completely
      effective due to increased resistance and varied susceptibility of fungi. Hence,
      the functional diversification study of novel targets has to be carried out. The
      enzyme glucosamine-6-phosphate synthase [EC 2.6.1.16], a novel drug target,
      catalyzes the rate-limiting step of the fungal cell-wall biosynthetic pathway,
      comprising four conserved domains, two glutaminase and sugar-isomerising (SIS)
      domains with active site. The amino acids within these domains tend to mutate
      simultaneously and exert mutual selective forces which might result in untoward
      fungal adaptations that are fixed through random genetic drift over time. The
      current study is an attempt to investigate such 'non-independent' coevolving
      residues which play critical functional and structural role in the protein.
      Residues with Shannon entropy ?1 (calculated by the Protein Variability Server)
      were considered and subsequently, positional correlations were estimated by
      InterMap3D 1.3 server. It was observed that majority of coevolving pairs of first
      SIS domain involved interactions with hydrophobic leucine and found to be
      spatially coupled in 3-dimensional structure of the enzyme. The coevolving groups
      of Aspergillus niger and Rhizopus oryzae species might play a role in drug
      resistance. Such coevolutionary analysis is important for understanding the
      receptor-ligand interactions and effective drug designing.

PMID- 21904432
TI  - A comprehensive molecular interaction map for Hepatitis B virus and drug
      designing of a novel inhibitor for Hepatitis B X protein.
AB  - Hepatitis B virus (HBV) infection is a leading source of liver diseases such as
      hepatitis, cirrhosis and hepatocellular carcinoma. In this study, we use
      computation methods in order to improve our understanding of the complex
      interactions that occur between molecules related to Hepatitis B virus (HBV). Due
      to the complexity of the disease and the numerous molecular players involved, we
      devised a method to construct a systemic network of interactions of the processes
      ongoing in patients affected by HBV. The network is based on high-throughput
      data, refined semi-automatically with carefully curated literature-based
      information. We find that some nodes in the network that prove to be
      topologically important, in particular HBx is also known to be important target
      protein used for the treatment of HBV. Therefore, HBx protein is the preferential
      choice for inhibition to stop the proteolytic processing. Hence, the 3D structure
      of HBx protein was downloaded from PDB. Ligands for the active site were designed
      using LIGBUILDER. The HBx protein's active site was explored to find out the
      critical interactions pattern for inhibitor binding using molecular docking
      methodology using AUTODOCK Vina. It should be noted that these predicted data
      should be validated using suitable assays for further consideration.

PMID- 21904433
TI  - Insights from the analysis of conserved motifs and permitted amino acid exchanges
      in the human, the fly and the worm GPCR clusters.
AB  - G-protein coupled receptors (GPCRs) belong to biologically important and
      functionally diverse and largest super family of membrane proteins. GPCRs retain
      a characteristic membrane topology of seven alpha helices with three
      intracellular, three extracellular loops and flanking N' and C' terminal
      residues. Subtle differences do exist in the helix boundaries (TM-domain), loop
      lengths, sequence features such as conserved motifs, and substituting amino acid
      patterns and their physiochemical properties amongst these sequences (clusters)
      at intra-genomic and inter-genomic level (please re-phrase into 2 statements for
      clarity). In the current study, we employ prediction of helix boundaries and
      scores derived from amino acid substitution exchange matrices to identify the
      conserved amino acid residues (motifs) as consensus in aligned set of homologous
      GPCR sequences. Co-clustered GPCRs from human and other genomes, organized as 32
      clusters, were employed to study the amino acid conservation patterns and species
      specific or cluster-specific motifs. Critical analysis on sequence composition
      and properties provide clues to connect functional relevance within and across
      genome for vast practical applications such as design of mutations and
      understanding of disease-causing genetic abnormalities.

PMID- 21904434
TI  - Molecular modeling of human neutral sphingomyelinase provides insight into its
      molecular interactions.
AB  - The neutral sphingomyelinase (N-SMase) is considered a major candidate for
      mediating the stress-induced production of ceramide, and it plays an important
      role in cell-cycle arrest, apoptosis, inflammation, and eukaryotic stress
      responses. Recent studies have identified a small region at the very N-terminus
      of the 55 kDa tumour necrosis factor receptor (TNF-R55), designated the neutral
      sphingomyelinase activating domain (NSD) that is responsible for the TNF-induced
      activation of N-SMase. There is no direct association between TNF-R55 NSD and N
      SMase; instead, a protein named factor associated with N-SMase activation (FAN)
      has been reported to couple the TNF-R55 NSD to N-SMase. Since the three
      dimensional fold of N-SMase is still unknown, we have modeled the structure using
      the protein fold recognition and threading method. Moreover, we propose models
      for the TNF-R55 NSD as well as the FAN protein in order to study the structural
      basis of N-SMase activation and regulation. Protein-protein interaction studies
      suggest that FAN is crucially involved in mediating TNF-induced activation of the
      N-SMase pathway, which in turn regulates mitogenic and proinflammatory responses.
      Inhibition of N-SMase may lead to reduction of ceramide levels and hence may
      provide a novel therapeutic strategy for inflammation and autoimmune diseases.
      Molecular dynamics (MD) simulations were performed to check the stability of the
      predicted model and protein-protein complex; indeed, stable RMS deviations were
      obtained throughout the simulation. Furthermore, in silico docking of low
      molecular mass ligands into the active site of N-SMase suggests that His135,
      Glu48, Asp177, and Asn179 residues play crucial roles in this interaction. Based
      on our results, these ligands are proposed to be potent and selective N-SMase
      inhibitors, which may ultimately prove useful as lead compounds for drug
      development.

PMID- 21904435
TI  - Remote homologue identification of Drosophila GAGA factor in mouse.
AB  - GAGA factor (GAF) is involved in both gene activation and gene repression and
      plays a role in the modulation of chromatin structure. In Drosophila, Trithroax
      like (Trl) gene encodes the DNA binding protein called GAGA factor (GAF). Trl-GAF
      binds to GAGA sites through its C2H2 zinc finger domain and has an N-terminal
      BTB/POZ domain. Identification of Trl-GAF homologue in mouse helps in deeper
      understanding of the mechanism and function. Conventional alignment tools such as
      BLAST and FASTA cannot identify homologues in mouse genome as their sequence
      identity is below 30%. In the present study, various sequence and structure
      analyses were followed for the detection of remote homologues of Drosophila GAGA
      FACTOR in mouse to identify as Zbtb3. Through homology modeling and docking
      approach, the zinc finger region of mouse Zbtb3 showed conserved residues and
      favorable DNA binding sites with GAGA sites similar to that of Drosophila GAGA
      FACTOR.

PMID- 21904436
TI  - Adaptive thresholds to detect differentially expressed genes in microarray data.
AB  - To detect changes in gene expression data from microarrays, a fixed threshold for
      fold difference is used widely. However, it is not always guaranteed that a
      threshold value which is appropriate for highly expressed genes is suitable for
      lowly expressed genes. In this study, aiming at detecting truly differentially
      expressed genes from a wide expression range, we proposed an adaptive threshold
      method (AT). The adaptive thresholds, which have different values for different
      expression levels, are calculated based on two measurements under the same
      condition. The sensitivity, specificity and false discovery rate (FDR) of AT were
      investigated by simulations. The sensitivity and specificity under various noise
      conditions were greater than 89.7% and 99.32%, respectively. The FDR was smaller
      than 0.27. These results demonstrated the reliability of the method.

PMID- 21904437
TI  - ValFold: Program for the aptamer truncation process.
AB  - DNA or RNA aptamers have gained attention as the next generation antibody-like
      molecules for medical or diagnostic use. Conventional secondary structure
      prediction tools for nucleic acids play an important role to truncate or minimize
      sequence, or introduce limited chemical modifications without compromising or
      changing its binding affinity to targets in the design of improved aptamers
      selected by Systematic Evolution of Ligands by EXponential enrichment (SELEX). We
      describe a novel software package, ValFold, capable of predicting secondary
      structures with improved accuracy based on unique aptamer characteristics.
      ValFold predicts not only the canonical Watson-Crick pairs but also G-G pairs
      derived from G-quadruplex (known structure for many aptamers) using the stem
      candidate selection algorithm. AVAILABILITY: The database is available for free
      at http://code.google.com/p/valfold/

PMID- 21904438
TI  - Antagomirbase- a putative antagomir database.
AB  - The accurate prediction of a comprehensive set of messenger putative antagomirs
      against microRNAs (miRNAs) remains an open problem. In particular, a set of
      putative antagomirs against human miRNA is predicted in this current version of
      database. We have developed Antagomir database, based on putative antagomirs
      miRNA heterodimers. In this work, the human miRNA dataset was used as template to
      design putative antagomirs, using GC content and secondary structures as
      parameters. The algorithm used predicted the free energy of unbound antagomirs.
      Although in its infancy the development of antagomirs, that can target cell
      specific genes or families of genes, may pave the way forward for the generation
      of a new class of therapeutics, to treat complex inflammatory diseases. Future
      versions need to incorporate further sequences from other mammalian homologues
      for designing of antagomirs for aid in research. AVAILABILITY: The database is
      available for free at
      http://bioinfopresidencycollegekolkata.edu.in/antagomirs.html.

PMID- 21904439
TI  - DEB: A web interface for RNA-seq digital gene expression analysis.
AB  - Digital expression (DE) is an important application of RNA-seq technology to
      quantify the transcriptome. The number of mapped reads to each transcript or gene
      varies under different conditions and replicates. Currently, three different
      statistical algorithms (edgeR, DESeq and bayseq) are available as R packages, to
      compare the reads to identify significantly expressed transcripts or genes. So
      far, users have to manually install and run each R package separately. It is also
      of users' interest to compare the results of different approaches. Here, we
      present a pipeline DEB which automates all the steps in file preparation,
      computation and result comparison. AVAILABILITY: The database is available for
      free at http://www.ijbcb.org/DEB/php/onlinetool.php.

PMID- 21904440
TI  - Penalized variable selection with U-estimates.
AB  - U-estimates are defined as maximizers of objective functions that are U
      statistics. As an alternative to M-estimates, U-estimates have been extensively
      used in linear regression, classification, survival analysis, and many other
      areas. They may rely on weaker data and model assumptions and be preferred over
      alternatives. In this article, we investigate penalized variable selection with U
      estimates. We propose smooth approximations of the objective functions, which can
      greatly reduce computational cost without affecting asymptotic properties. We
      study penalized variable selection using penalties that have been well
      investigated with M-estimates, including the LASSO, adaptive LASSO, and bridge,
      and establish their asymptotic properties. Generically applicable computational
      algorithms are described. Performance of the penalized U-estimates is assessed
      using numerical studies.

PMID- 21904441
TI  - Abdominal-pelvic actinomycosis mimicking malignant neoplasm.
AB  - Abdominal-pelvic actinomycosis is often mistaken for other conditions, presenting
      a preoperative diagnostic challenge. In a 46-year-old female, computed tomography
      showed an abdominal-pelvic retroperitoneal mass extending from the lower pole of
      the right kidney to the lower pelvis. The patient had a 3-year history of
      intrauterine device. The mass appeared to involve the ascending colon, cecum,
      distal ileum, right Fallopian tube and ovary, and ureter anteriorly and the psoas
      muscle posteriorly. The resection of retroperitoneal mass, distal ileum
      appendicectomy, right hemicolectomy, and right salpingo-oophorectomy was
      performed. The postoperative period was uneventful. Penicillin therapy was given
      for six months without any complication. The retroperitoneal mass measured 4.5 *
      3.5 * 3 cm, surrounded adjacent organs and histologically showed inflammatory
      granulomatous tissue, agglomeration of filaments, and sulfur granules of
      Actinomyces, with positive reaction with periodic acid Schiff. Right tubo-ovarian
      abscess was present. Abdominalpelvic actinomycosis should always be considered in
      patients with a pelvic mass especially in ones using intrauterine device.

PMID- 21904442
TI  - Diagnosis and management of cystic lesions of the pancreas.
AB  - Pancreatic cysts are challenging lesions to diagnose and to treat. Determining
      which of the five most common diagnoses-pancreatic pseudocyst, serous cystic
      neoplasm (SCN), solid pseudopapillary neoplasm (SPN), mucinous cystic neoplasm
      (MCN), and intraductal mucinous papillary neoplasm (IPMN)-is likely the correct
      one requires the careful integration of many historical, radiographic,
      laboratory, and other factors, and management is markedly different depending on
      the type of cystic lesion of the pancreas. Pseudocysts are generally
      distinguishable based on historical, clinical and radiographic characteristics,
      and among the others, the most important differentiation is between the mucin
      producing MCN and IPMN (high risk for cancer) versus the serous SCN and SPN (low
      risk for cancer). EUS with FNA and cyst-fluid analysis will continue to play an
      important role in diagnosis. Among mucinous lesions, those that require treatment
      (resection currently) are any MCN, any MD IPMN, and BD IPMN larger than 3 cm,
      symptomatic, or with an associated mass, with the understanding that SCN or
      pseudocysts may be removed inadvertently due to diagnostic inaccuracy, and that a
      certain proportion of SPN will indeed be malignant at the time of removal. The
      role of ethanol ablation is under investigation as an alternative to resection in
      selected patients.

PMID- 21904443
TI  - Improving antigenicity of the recombinant hepatitis C virus core protein via
      random mutagenesis.
AB  - In order to enhance the sensitivity of diagnosis, a recombinant clone containing
      domain I of HCV core (amino acid residues 1 to 123) was subjected to random
      mutagenesis. Five mutants with higher sensitivity were obtained by colony
      screening of 616 mutants using reverse ELISA. Sequence analysis of these mutants
      revealed alterations focusing on W(84), P(95), P(110), or V(129). The inclusion
      bodies of these recombinant proteins overexpressed in E. coli BL21(DE3) were
      subsequently dissolved using 6 M urea and then refolded by stepwise dialysis.
      Compared to the unfolded wild-type antigen, the refolded M3b antigen (W(84)S,
      P(110)S and V(129)L) exhibited an increase of 66% antigenicity with binding
      capacity of 0.96 and affinity of 113 MUM(-1). Moreover, the 33% decrease of the
      production demand suggests that M3b is a potential substitute for anti-HCV
      antibody detection.

PMID- 21904444
TI  - Natural killer cells in healthy and diseased subjects.

PMID- 21904445
TI  - Th subset balance in lupus nephritis.
AB  - Lupus nephritis, which has various histological patterns and variable clinical
      outcomes, is one of the most important complications of systemic lupus nephritis
      (SLE). This pathogenetic mechanism in each histologically different type of lupus
      nephritis (LN) remains unclear. Although SLE is suggested to be a Th2-driven
      disease, elevation of both Th1 and Th2 cytokines occurs in both humans and mice,
      suggesting that SLE is a complex disease driven by different lymphocyte subsets
      with high heterogeneity of clinical manifestations and organ involvement. Recent
      findings in LN elucidate an essential role for the Th1, IL-17 producing T cells
      and Th17 cells in the development of diffuse proliferative lupus nephritis
      (DPLN), and Th2 cytokine in that of membranous lupus nephritis (MLN). These data
      support the hypothesis that individual Th1/Th2 balance is one of the critical
      determinants for histopathology of LN.

PMID- 21904446
TI  - A Model for NAD(P)H:Quinoneoxidoreductase 1 (NQO1) Targeted Individualized Cancer
      Chemotherapy.
AB  - NQO1 (NAD(P)H:quinoneoxidoreductase 1) is a reductive enzyme that is an important
      activator of bioreductive antitumor agents. NQO1 activity varies in individual
      tumors but is generally higher in tumor cells than in normal cells. NQO1 has been
      used as a target for tumor specific drug development. We investigated a series of
      bioreductive benzoquinone mustard analogs as a model for NQO1 targeted
      individualized cancer chemotherapy. We compared the tumor cell growth inhibitory
      activity of benzoquinone mustard analogs with sterically bulky groups of
      different size and placed at different positions on the benzoquinone ring, using
      tumor cell lines with different levels of NQO1. We demonstrated that functional
      groups of different steric size could be used to produce a series of bioreductive
      antitumor agents that were activated by different levels of NQO1 in tumor cells.
      This series of drugs could then be used to target cells with specific levels of
      NQO1 for growth inhibition and to avoid damage to normal cells, like bone marrow
      cells, that have low levels of NQO1. This approach could be used to develop new
      bioreductive antitumor agents for NQO1 targeted individualized cancer
      chemotherapy.

PMID- 21904447
TI  - The effect of valproic Acid on mesenchymal pluripotent cell proliferation and
      differentiation in extracellular matrices.
AB  - Valproic acid (2-n-propylpentanoic acid, VPA) is a widely used antiepileptic and
      anticonvulsant drug. Previous studies have reported that VPA effects osteogenesis
      in vivo and in vitro, yet it remains unclear whether VPA promotes cell
      differentiation of osteoblasts derived from mesenchymal cells. The purpose of
      this study was to clarify the effect of VPA on undifferentiated pluripotent
      mesenchymal cell proliferation and differentiation into osteoblasts while
      analyzing the impact of the absence or presence of extracellular matrices (ECMs).
      Mouse mesenchymal cells were cultured on non-coated plastic, type I collagen
      coated, and fibronectin-coated plates in the absence or presence of VPA. A cell
      proliferation assay was performed in which modified formazan dye content was
      analyzed and proliferation nuclear antigen (PCNA)-positive cells were counted at
      various concentrations of VPA. A high concentration of VPA did not clearly alter
      cell morphology, but large numbers of stress fibers were observed in these cells
      and the cell proliferation ratio was decreased with positive PCNA counts. In the
      presence of matrices, the cell proliferation ratio decreased at low VPA
      concentrations compared with the ratio obtained in the absence of these ECMs. On
      the other hand, VPA promoted osteoblastic differentiation in the presence of type
      I collagen. These findings indicate that for undifferentiated mesenchymal cells,
      VPA promotes a decrease in the cell proliferation rate in the presence of ECMs
      and promotes osteoblastic differentiation, both of which could provide insight
      into additional mechanisms of osteoblastic cell differentiation caused by VPA.

PMID- 21904448
TI  - Comment: update on the management of constipation in the elderly: new treatment
      options.

PMID- 21904449
TI  - Convection-enhanced delivery of methotrexate-loaded maghemite nanoparticles.
AB  - Convection-enhanced delivery (CED) is a novel approach for delivering drugs
      directly into brain tumors by intracranial infusion, enabling the distribution of
      high drug concentrations over large tissue volumes. This study was designed to
      present a method for binding methotrexate (MTX) to unique crystalline, highly
      ordered and superparamagnetic maghemite nanoparticles via human serum albumin
      (HSA) coating, optimized for CED treatments of gliomas. Naked nanoparticles and
      HSA- or polyethylene glycol (PEG)-coated nanoparticles with/without MTX were
      studied. In vitro results showed no toxicity and a similar cell-kill efficacy of
      the MTX-loaded particles via HSA coating to that of free MTX, while MTX-loaded
      particles via PEG coating showed low efficacy. In vivo, the PEG-coated
      nanoparticles provided the largest distributions in normal rat brain and long
      clearance times, but due to their low efficacy in vitro, were not considered
      optimal. The naked nanoparticles provided the smallest distributions and shortest
      clearance times. The HSA-coated nanoparticles (with/without MTX) provided good
      distributions and long clearance times (nearly 50% of the distribution volume
      remained in the brain 3 weeks post treatment). No MTX-related toxicity was noted.
      These results suggest that the formulation in which HSA was bound to our
      nanoparticles via a unique precipitation method, and MTX was bound covalently to
      the HSA, could enable efficient and stable drug loading with no apparent
      toxicity. The cell-kill efficacy of the bound MTX remained similar to that of
      free MTX, and the nanoparticles presented efficient distribution volumes and slow
      clearance times in vivo, suggesting that these particles are optimal for CED.

PMID- 21904450
TI  - Transdermal delivery of paeonol using cubic gel and microemulsion gel.
AB  - BACKGROUND: The aim of this study was to develop new systems for transdermal
      delivery of paeonol, in particular microemulsion gel and cubic gel formulations.
      METHODS: Various microemulsion vehicles were prepared using isopropyl myristate
      as an oil phase, polyoxyethylated castor oil (Cremophor((r)) EL) as a surfactant,
      and polyethylene glycol 400 as a cosurfactant. In the optimum microemulsion gel
      formulation, carbomer 940 was selected as the gel matrix, and consisted of 1%
      paeonol, 4% isopropyl myristate, 28% Cremophor EL/polyethylene glycol 400 (1:1),
      and 67% water. The cubic gel was prepared containing 3% paeonol, 30% water, and
      67% glyceryl monooleate. RESULTS: A skin permeability test using excised rat
      skins indicated that both the cubic gel and microemulsion gel formulations had
      higher permeability than did the paeonol solution. An in vivo pharmacokinetic
      study done in rats showed that the relative bioavailability of the cubic gel and
      microemulsion gel was enhanced by about 1.51-fold and 1.28-fold, respectively,
      compared with orally administered paeonol suspension. CONCLUSION: Both the cubic
      gel and microemulsion gel formulations are promising delivery systems to enhance
      the skin permeability of paeonol, in particular the cubic gel.

PMID- 21904451
TI  - Microemulsion-based novel transdermal delivery system of tetramethylpyrazine:
      preparation and evaluation in vitro and in vivo.
AB  - OBJECTIVE: To deliver 2,3,5,6-tetramethylpyrazine (TMP) in a relatively large
      dose through a transdermal route and facilitate the practical application of
      microemulison in transdermal drug delivery. METHODS: The pseudo-ternary phase
      diagram for microemulsion regions was constructed using isopropyl myristate as
      oil phase, Labrasol((r)) as surfactant, and Plurol((r)) Oleique CC 497 as
      cosurfactant. A uniform experimental design was applied for formulation
      optimization. In vitro skin permeation experiments of six formulations were
      undertaken with TMP transdermal patch (EUDRAGIT((r)) E100 as matrix) and TMP
      saturated solution as controls. We prepared TMP-oil dispersed in water-ethylene
      vinyl acetate-transdermal therapeutic system (TMP-O/W-EVA-TTS) with microemulsion
      as reservoir and EVA membrane as release liner; pharmacokinetic and brain
      distribution studies in rats were conducted with TMP transdermal patches as
      control. RESULTS: The skin fluxes of TMP from microemulsions were 8.2- to 26.7
      fold and 0.9- to 4.7-fold higher than those of TMP transdermal patch and TMP
      saturated solution, respectively, and were strongly affected by the microemulsion
      composition. The improvement in TMP solubility as well as the skin permeation
      enhancement effect of microemulsion components contributed mainly to transdermal
      delivery facilitation. In the pharmacokinetic study, the relative bioavailability
      of TMP-O/W-EVA-TTS was 350.89% compared with the TMP transdermal patch. Higher
      and more stable TMP contents in rat plasma were obtained after administration of
      TMP-O/WEVA- TTS than after application of TMP transdermal patch. In the brain
      distribution study, higher rate and extent of TMP distribution to brain, and
      lower rate of TMP clearance from brain were observed after transdermal
      administration of TMP-O/W-EVA-TTS than after application of TMP transdermal
      patch. CONCLUSION: The novel transdermal delivery system prepared in this study
      showed a remarkable skin permeation improvement of microemulsion and facilitated
      its practical application in transdermal drug delivery. With this system as a
      vehicle, a relatively large dose of TMP could enable successful drug delivery via
      the transdermal route.

PMID- 21904452
TI  - Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles
      for topical delivery.
AB  - BACKGROUND: The purpose of this study was to investigate lecithin-chitosan
      nanoparticles as a topical delivery system for quercetin. METHODS: Tocopheryl
      propylene glycol succinate was chosen to be the surfactant for the nanosystem.
      The mean particle size of the nanoparticles was 95.3 nm, and the entrapment
      efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively.
      Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was
      evaluated using quercetin propylene glycol solution as the control. RESULTS:
      Compared with quercetin solution, the quercetin-loaded nanoparticles showed
      higher permeation ability, and significantly increased accumulation of quercetin
      in the skin, especially in the epidermis. Microstructure observation of the skin
      surface after administration indicated that the interaction between ingredients
      of the nanoparticles and the skin surface markedly changed the morphology of the
      stratum corneum and disrupted the corneocyte layers, thus facilitating the
      permeation and accumulation of quercetin in skin. CONCLUSION: Lecithin-chitosan
      nanoparticles are a promising carrier for topical delivery of quercetin.

PMID- 21904453
TI  - Improvement of effect of water-in-oil microemulsion as an oral delivery system
      for fexofenadine: in vitro and in vivo studies.
AB  - Fexofenadine (FEX) has high solubility and low permeability (BCS, Class III). In
      this work, novel FEX loaded water in oil microemulsion (w/o) was designed to
      improve bioavailability and compared with Fexofen((r)) syrup in in vitro and in
      vivo studies. In addition, pharmacokinetic parameters in permeability studies
      were estimated by using WinNonLin software program. w/o microemulsion system was
      optimized using a pseudoternary phase diagram, composed of span 80/lutrol F 68
      (9.5:0.5 w/w), oleic acide, isopropyl alcohol and water as surfactant mixture;
      oil and cosurfactant was developed for oral drug delivery. w/o microemulsion
      systems were characterized by phase behavior, particle size, viscosity and
      solubilization capacity. In vitro studies were studied using Caco-2 cell
      monolayer. Pharmacokinetic parameters of w/o microemulsion were investigated in
      rabbits and compared to Fexofen((r)) syrup. Fexofen((r)) syrup and microemulsion
      were administered by oral gavage at 6 mg/kg of the same concentration. The
      experimental results indicated that microemulsion (HLB = 5.53) formed nanometer
      sized droplets (33.29 +/- 1.76) and had good physical stability. This
      microemulsion increased the oral bioavailability of FEX which was highly water
      soluble but fairly impermeable. The relative bioavailability of FEX microemulsion
      was about 376.76% compared with commercial syrup in rabbits. In vitro experiments
      were further employed for the enhanced effect of the microemulsion for FEX. These
      results suggest that novel w/o microemulsion plays an important role in enhancing
      oral bioavailability of low permeability drugs.

PMID- 21904454
TI  - Synthesis and properties of a novel biodegradable poly(ester amine) copolymer
      based on poly(L-lactide) and low molecular weight polyethylenimine for gene
      delivery.
AB  - BACKGROUND: Gene therapy is a promising approach to the treatment of a wide range
      of diseases. The development of efficient and adequate gene delivery systems
      could be one of the most important factors. Polyethyleneimine, a cationic
      polymer, is one of the most successful and widely used vectors for nonviral
      transfection in vitro and in vivo. METHODS: A novel biodegradable poly(ester
      amine) copolymer (PEA) was successfully prepared from low molecular weight
      polyethylenimine (PEI, 2000 Da) and poly(L-lactide) copolymers. RESULTS:
      According to the results of agarose gel electrophoresis, particle size and zeta
      potential measurement, and transfection efficiency, the PEA copolymers showed a
      good ability to condense plasmid DNA effectively into nanocomplexes with a small
      particle size (<=150 nm) and moderate zeta potential (>=10 mV) at an appropriate
      polymeric carrier/DNA weight ratio. Compared with high molecular weight PEI
      (25kDa), the PEA obtained showed relatively high gene transfection efficiency as
      well as low cytotoxicity in vitro. CONCLUSION: These results indicate that such
      PEA might have potential application as a gene delivery system.

PMID- 21904455
TI  - HA/nylon 6,6 porous scaffolds fabricated by salt-leaching/solvent casting
      technique: effect of nano-sized filler content on scaffold properties.
AB  - Nanohydroxyapatite (n-HA)/nylon 6,6 composite scaffolds were produced by means of
      the salt-leaching/solvent casting technique. NaCl with a distinct range size was
      used with the aim of optimizing the pore network. Composite powders with
      different n-HA contents (40%, 60%) for scaffold fabrication were synthesized and
      tested. The composite scaffolds thus obtained were characterized for their
      microstructure, mechanical stability and strength, and bioactivity. The
      microstructure of the composite scaffolds possessed a well-developed
      interconnected porosity with approximate optimal pore size ranging from 200 to
      500 MUm, ideal for bone regeneration and vascularization. The mechanical
      properties of the composite scaffolds were evaluated by compressive strength and
      modulus tests, and the results confirmed their similarity to cortical bone. To
      characterize bioactivity, the composite scaffolds were immersed in simulated body
      fluid for different lengths of time and results monitored by scanning electron
      microscopy and energy dispersive X-ray microanalysis to determine formation of an
      apatite layer on the scaffold surface.

PMID- 21904456
TI  - Development of small interfering RNA delivery system using PEI-PEG-APRPG polymer
      for antiangiogenic vascular endothelial growth factor tumor-targeted therapy.
AB  - BACKGROUND: Small interfering RNA (siRNA) can silence target genes in the
      cytoplasm and be a major tool in gene therapy. Vascular endothelial growth factor
      (VEGF), a potent regulator of angiogenesis, is overexpressed in most tumors and
      is closely associated with tumor growth and metastasis. It has been shown that
      inhibition of VEGF expression by siRNA is an effective and useful method for
      antiangiogenic tumor therapy. METHODS: In the present study, we synthesized a
      targeted delivery system of PEI-PEG-APRPG incorporating angiogenic vessel-homing
      Ala-Pro-Arg-Pro-Gly (APRPG) peptide into cationic polyethylenimine (PEI) via a
      hydrophilic poly(ethylene glycol) (PEG) spacer. RESULTS: PEI-PEG-APRPG
      effectively condensed siRNA into 20-50 nm nanoparticles with a positive surface
      charge using a suitable N/P ratio. The siRNA/PEI-PEG-APRPG complex effectively
      enhanced the stability of siRNA in RNase A, and improved the proliferation
      inhibiting ability and transfection efficiency of siRNA in vitro and tumor
      accumulation in vivo. In addition, the siRNA/PEI-PEG-APRPG complex exhibited high
      efficiency as antitumor therapy with regard to tumor growth, microvessel density,
      and VEGF protein and mRNA levels. CONCLUSION: These findings suggest that PEI-PEG
      APRPG effectively delivers siRNA to tumors overexpressing VEGF and thereby
      inhibits tumor growth.

PMID- 21904457
TI  - Advances in cancer therapy through the use of carbon nanotube-mediated targeted
      hyperthermia.
AB  - Carbon nanotubes (CNTs) are emerging versatile tools in nanomedicine
      applications, particularly in the field of cancer targeting. Due to diverse
      surface chemistry and unique thermal properties, CNTs can act as strong optical
      absorbers in near infrared light where biological systems prove to be highly
      transparent. The process of laser-mediated ablation of cancer cells marked with
      biofunctionalized CNTs is frequently termed "nanophotothermolysis." This paper
      illustrates the potential of engineered CNTs as laser-activated photothermal
      agents for the selective nanophotothermolysis of cancer cells.

PMID- 21904458
TI  - Treatment of drug-resistant tuberculosis.
AB  - CLINICAL QUESTION: What is the best approach to the treatment of drug-resistant
      tuberculosis (TB)? RESULTS: Evidence-based treatment of drug-susceptible TB is
      the best means of preventing the development of drug-resistant disease.
      Suspecting the possibility of drug-resistant TB, and prompt detection of all
      forms of drug-resistant TB, not only multidrug-resistant and extensively drug
      resistant TB, should be part of the algorithm for diagnosis and management of all
      patients with active TB. IMPLEMENTATION: Treatment of all forms of drug-resistant
      TB must be tailored to the specific form of resistance with appropriate and
      effective drug regimens.

PMID- 21904460
TI  - Impact of restriction of cefepime use on the antimicrobial susceptibility of Gram
      negative bacilli related to healthcare-associated infections in an orthopedic
      hospital.
AB  - INTRODUCTION: In recent decades, antimicrobial resistance has become a public
      health problem, particularly in cases of healthcare-associated infections.
      Interaction between antibiotic consumption and resistance development is of
      particular interest regarding Gram-negative bacilli, whose growing resistance has
      represented a great challenge. OBJECTIVE: Assess the impact of restriction of
      cefepime use on antimicrobial susceptibility among the Gram-negative bacilli
      (GNB) most frequently involved in healthcare-associated infections (HAI).
      METHODS: DATA RELATING TO HOSPITAL OCCUPANCY AND MORTALITY RATES, INCIDENCE OF
      HAI, INCIDENCE OF GNB AS CAUSATIVE AGENTS OF HAI, ANTIMICROBIAL CONSUMPTION AT
      THE HOSPITAL AND ANTIMICROBIAL SUSCEPTIBILITY OF GNB RELATED TO HAI WERE COMPARED
      BETWEEN TWO PERIODS: a 24-month period preceding restriction of cefepime use and
      a 24-month period subsequent to this restriction. RESULTS: There was a
      significant drop in cefepime consumption after its restriction. Susceptibility of
      Acinetobacter baumanii improved relating to gentamicin, but it worsened in
      relation to imipenem, subsequent to this restriction. For Pseudomonas aeruginosa,
      there was no change in antimicrobial susceptibility. For Klebsiella pneumoniae
      and Enterobacter spp, there were improvements in susceptibility relating to
      ciprofloxacin. CONCLUSION: Restriction of cefepime use had a positive impact on
      K. pneumoniae and Enterobacter spp, given that after this restriction, their
      susceptibilities to ciprofloxacin improved. However, for A. baumanii, the impact
      was negative, given the worsening of susceptibility to imipenem.

PMID- 21904459
TI  - Critical appraisal of a quadrivalent CRM(197) conjugate vaccine against
      meningococcal serogroups A, C W-135 and Y (Menveo) in the context of treatment
      and prevention of invasive disease.
AB  - Worldwide, invasive meningococcal disease affects about 500,000 people annually.
      Case fatality in developed countries averages 10%, and higher rates are reported
      in less prosperous regions. According to the World Health Organization, the most
      important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features
      of invasive meningococcal disease make diagnosis and management difficult.
      Antibiotic measures are recommended for prophylaxis after exposure and for
      treatment of invasive meningococcal disease cases; however, resistant strains may
      be emerging. Vaccines are generally regarded as the best preventative measure for
      invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C,
      W-135, and Y using protein conjugation technology have clear advantages over
      older plain polysaccharide formulations without a protein component. The first
      quadrivalent meningococcal conjugate vaccine (MenACWY-D) was licensed in the US
      in 2005. More recently, MenACWY-CRM (Menveo((r))) was licensed in Europe, the US,
      the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197,
      a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers
      robust immunogenicity in all age groups, with a tolerability profile similar to
      that of a plain polysaccharide vaccine. Given its potential for protecting
      persons from infancy to old age, MenACWY-CRM offers the opportunity to protect
      broad populations against invasive meningococcal disease. The most optimal
      strategy for use of the vaccine has to be assessed country by country on the
      basis of local epidemiology, individual health care systems, and need.

PMID- 21904461
TI  - Similarity of hydrolyzing activity of human and rat small intestinal
      disaccharidases.
AB  - BACKGROUND: The purpose of this study was to clarify whether it is possible to
      extrapolate results from studies of the hydrolyzing activity of disaccharidases
      from rats to humans. MATERIALS AND METHODS: We measured disaccharidase activity
      in humans and rats using identical preparation and assay methods, and
      investigated the similarity in hydrolyzing activity. Small intestinal samples
      without malignancy were donated by five patients who had undergone bladder tumor
      surgery, and homogenates were prepared to measure disaccharidase activity. Adult
      rat homogenates were prepared using small intestine. RESULTS: Maltase activity
      was the highest among the five disaccharidases, followed by sucrase and then
      palatinase in humans and rats. Trehalase activity was slightly lower than that of
      palatinase in humans and was similar to that of sucrase in rats. Lactase activity
      was the lowest in humans, but was similar to that of palatinase in rats. Thus,
      the hydrolyzing activity of five disaccharidases was generally similar in humans
      and rats. The relative activity of sucrose and palatinase versus maltase was
      generally similar between humans and rats. The ratio of rat to human hydrolyzing
      activity of maltase, sucrase, and palatinase was 1.9-3.1, but this was not a
      significant difference. Leaf extract from Morus alba strongly inhibited the
      activity of maltase, sucrase, and palatinase, but not trehalase and lactase, and
      the degree of inhibition was similar in humans and rats. L-arabinose mildly
      inhibited sucrase activity, but hardly inhibited the activity of maltase,
      palatinase, trehalase and lactase in humans and rats. The digestibility of 1
      kestose, galactosylsucrose, and panose by small intestinal enzymes was very
      similar between humans and rats. CONCLUSION: These results demonstrate that the
      digestibility of newly developed saccharide materials evaluated by rat small
      intestinal enzymes can substitute for evaluation using human enzymes.

PMID- 21904462
TI  - Update on the management of inflammatory bowel disease: specific role of
      adalimumab.
AB  - Anti-tumor necrosis factor alpha (TNF-alpha) medications are a class of biologics
      employed in the treatment of patients with inflammatory bowel disease (IBD).
      Adalimumab is the first fully human monoclonal immunoglobulin directed against
      TNF-alpha, which binds with high affinity and specificity to membrane and soluble
      TNF. Adalimumab administered subcutaneously has demonstrated efficacy in the
      treatment of rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis,
      and severe chronic psoriasis. Studies have shown that adalimumab is effective for
      inducing and maintaining remission of moderate-to-severe active Crohn's disease
      (CD) patients at an induction dose of 160/80 mg (week 0 and 2) and at a
      maintenance dose of 40 mg every other week. The efficacy of adalimumab as a
      second-line therapy has also been documented for patients with loss of response
      or intolerance to infliximab. Adalimumab is also superior to placebo for inducing
      and maintaining complete perianal fistula closure. It also seems effective for
      reducing extraintestinal manifestations. The safety profile is similar to that of
      other anti-TNF therapy in CD patients, with lower immunogenicity and rate of
      adverse injection reactions than infliximab. Adalimumab is not approved for the
      treatment of ulcerative colitis (UC). Recently, however, the results of the first
      randomized, controlled trial on adalimumab for UC showed that adalimumab at
      160/80 mg induction dose was safe and effective for inducing remission and
      clinical response after 8 weeks in patients with moderately-to-severely active UC
      failing treatment with corticosteroids and/or immunosuppressants. More data are
      necessary to clarify the therapeutic role of adalimumab in UC. This review of the
      literature summarizes available data on the efficacy and safety profile
      adalimumab in patients with IBD.

PMID- 21904463
TI  - Assessing patients' satisfaction with anti-TNFalpha treatment in Crohn's disease:
      qualitative steps of the development of a new questionnaire.
AB  - PURPOSE: To develop a self-administered questionnaire assessing patients'
      satisfaction with treatments in Crohn's disease for use in clinical research and
      epidemiological studies. PATIENTS AND METHODS: Semi-directive interviews (16)
      were conducted with patients with severe Crohn's disease treated with anti-tumor
      necrosis factor alpha (anti-TNFalpha). Transcripts were analyzed and concepts
      related to satisfaction with treatment were extracted and organized into a model.
      Items were generated using patients' words. The resulting test version was tested
      for relevance and comprehension with 7 patients and revised accordingly; the new
      version was tested with 5 other patients and revised to provide the pilot
      version. A clinician advisory board was involved at each milestone of the
      development. RESULTS: The test questionnaire assessed treatment satisfaction
      through 67 items, organized into 5 sections: treatment efficacy, side-effects,
      convenience and constraints, overall impact, and satisfaction. Conceptual content
      of the questionnaire includes comparison with prior state and with expectations,
      satisfaction, acceptability, and intentions. The questionnaire was generally well
      accepted and understood by patients; few modifications were made in the structure
      and item formulation. After the second round of comprehension tests, the pilot
      version contained 62 items; the questionnaire was named Satisfaction of PAtients
      in Crohn's diseasE (SPACE((c))). CONCLUSION: The questionnaire is a unique tool
      to assess treatment satisfaction in patients with Crohn's disease. A scoring and
      validation study is currently being performed to finalize and establish its
      scoring, as well as its psychometric properties.

PMID- 21904464
TI  - Trends in utilization and off-label use of polyethylene glycol 4000 laxatives and
      the prevalence of constipation in children in France.
AB  - PURPOSE: To determine trends in utilization and off-label use of polyethylene
      glycol (PEG) 4000 in children and to determine the prevalence of constipation.
      METHODS: Retrospective cross-sectional analyses were conducted from 1997 to 2007
      in a French health care database comprising general practitioners and
      pediatricians. Patients prescribed PEG 4000 (Forlax((r)); Ipsen Pharma, Paris,
      France) were used to assess PEG 4000 use; constipation was defined by a diagnosis
      of constipation or use of any laxative. Analyses used linear regression models to
      fit trends over time. RESULTS: The study sample consisted of a nationally
      representative sample of 1200 general practitioners with 1.6 million patient
      medical records and 100 pediatricians with 70,000 patient medical records. Data
      were available from 1997 to 2007 for general practitioners and from 2003 to 2007
      for pediatricians and were extrapolated to the national level. Among both groups
      of physicians there were statistically significant increases in the number of
      patients prescribed 4 g. For the 10 g dose, there was a decline among
      pediatricians. The largest increases were in children aged 0-8 years and in
      females. The prevalence of constipation in children aged 0-18 years was 4%.
      CONCLUSION: There has been an increase in the use of PEG 4000 laxative in
      children, particularly in the younger ages and in females. Use of the 4 g dose
      has increased. There was considerable off-label use of PEG 4000 in children aged
      0-8 years before the introduction of the 4 g pediatric dose, which reflected
      clinical need.

PMID- 21904465
TI  - Prevalence and factors associated with off-label antidepressant prescriptions for
      insomnia.
AB  - BACKGROUND: The primary objective of our study was to investigate the prevalence
      of off-label antidepressant drug use in insomnia. The secondary objective was to
      compare prescribing patterns between off-label antidepressants vs hypnotics
      approved by the US Food and Drug Administration for insomnia, with particular
      emphasis on socioeconomic characteristics of patients and physicians. METHODS: We
      undertook a secondary data analysis using the national longitudinal database from
      the 2006 National Ambulatory Medical Care Survey. Subjects were identified from
      outpatient visits in which at least one insomnia drug was prescribed. A series of
      weighted Chi-squared statistics was used to compare drug use for insomnia across
      various patient and physician characteristics. Multivariate logistic regression
      was conducted to identify factors associated with off-label antidepressant drug
      use. RESULTS: Among 901.95 million outpatient visits that took place in the US in
      2006, an estimated 30.43 million visits included at least one drug prescription
      for insomnia. Off-label antidepressants were prescribed significantly more
      frequently (45.1%) than nonbenzodiazepine z-hypnotics (43.2%) and benzodiazepines
      (11.7%). Insomnia prescribing patterns were significantly influenced by physician
      specialty and physician office settings. Pediatricians (odds ratio [OR]: 65.892;
      95% confidence interval [CI]: 5.536-810.564) and neurologists (OR: 4.784; 95% CI:
      2.044-11.201) were more likely to prescribe off-label antidepressants than
      psychiatrists. Self-paying patients were more likely to receive off-label
      antidepressants as treatment for insomnia than patients with private insurance
      (OR 2.594; 95% CI: 1.128-5.967). CONCLUSION: Our findings indicate significant
      socioeconomic disparities in the use of off-label antidepressants. Future studies
      might explore interventional and educational strategies to ensure well informed
      clinical decisions that can withstand pharmaceutical marketing strategies and
      diagnostic uncertainties regarding the treatment of insomnia.

PMID- 21904466
TI  - Should benefit-risk assessment have its own drug "label"?
AB  - Many consumers and clinicians incorrectly believe that the Food and Drug
      Administration (FDA) approval of a new therapeutic implies that its benefits have
      been proven to exceed its harms. While the FDA could require proof that benefits
      exceed harms prior to approval, it has been argued that this approach would be
      infeasible because of prohibitively large sample sizes. One possible alternative
      would be for the FDA to supplement its standard "label" denoting "safe and
      effective" with a secondary "label" denoting benefits have been demonstrated to
      exceed harms, which would be granted only after sufficient post-marketing data
      had accumulated to prove that its benefits exceeded its harms. This secondary
      label would not necessarily be linked to marketing restrictions or other
      commercial prohibitions but, rather, would be only information for consumers and
      clinicians. Strengths, weaknesses, and feasibility challenges of this approach
      are discussed.

PMID- 21904467
TI  - Trigeminal neuralgia: successful antiepileptic drug combination therapy in three
      refractory cases.
AB  - Antiepileptic drug combination therapy remains an empirical second-line treatment
      approach in trigeminal neuralgia, after treatment with one antiepileptic drug or
      other nonantiepileptic drugs have failed. The results in three patients followed
      in our clinic are not sufficient to draw definitive conclusions, but suggest the
      possibility of developing this type of therapeutic approach further.

PMID- 21904469
TI  - Automatic discrimination of the geographical origins of milks by excitation
      emission fluorescence spectrometry and chemometrics.
AB  - This paper presents the automatic discrimination of geographical origins of milks
      from Western Yunnan Plateau areas and eastern China by excitation-emission
      fluorescence spectrometry and chemometrics. Genuine plateau milks (n = 60) and
      milks from eastern China (n = 89) are scanned in the regions of 180-300 nm for
      excitation and 200-800 nm for emission. Different options of data analysis are
      investigated and compared in terms of their performance in discriminating milks
      of different geographical origins: (1) two-way partial least squares discriminant
      analysis (PLSDA) based on excitation and emission spectra, respectively; (2) two
      way PLSDA based on fusion of excitation and emission spectra; (3) three-way PLSDA
      based on excitation-emission matrix spectra. The two-way PLSDA methods with
      excitation spectra, emission spectra, and fusion of excitation and emission
      spectra correctly classify 91.3%, 88.6%, and 95.3% of the milk samples,
      respectively; while the total accuracy of three-way PLSDA is 96.0%. The results
      demonstrate the two-way data combining excitation and emission spectra are
      sufficient to characterize and identify the plateau milks. Considering both model
      accuracy and the analytical time required, two-way PLS-DA with fusion of
      excitation and emission spectra is recommended as a reliable and quick method to
      discriminate plateau milks from ordinary milks.

PMID- 21904471
TI  - Gastro-hep news.

PMID- 21904472
TI  - Treatment of gastroesophageal reflux disease in obese patients.

PMID- 21904470
TI  - The coevolution of phycobilisomes: molecular structure adapting to functional
      evolution.
AB  - Phycobilisome is the major light-harvesting complex in cyanobacteria and red
      alga. It consists of phycobiliproteins and their associated linker peptides which
      play key role in absorption and unidirectional transfer of light energy and the
      stability of the whole complex system, respectively. Former researches on the
      evolution among PBPs and linker peptides had mainly focused on the phylogenetic
      analysis and selective evolution. Coevolution is the change that the conformation
      of one residue is interrupted by mutation and a compensatory change selected for
      in its interacting partner. Here, coevolutionary analysis of allophycocyanin,
      phycocyanin, and phycoerythrin and covariation analysis of linker peptides were
      performed. Coevolution analyses reveal that these sites are significantly
      correlated, showing strong evidence of the functional and structural importance
      of interactions among these residues. According to interprotein coevolution
      analysis, less interaction was found between PBPs and linker peptides. Our
      results also revealed the correlations between the coevolution and adaptive
      selection in PBS were not directly related, but probably demonstrated by the
      sites coupled under physical-chemical interactions.

PMID- 21904473
TI  - Management of viral resistance in the therapy of chronic hepatitis B.

PMID- 21904468
TI  - A Role for Sigma Receptors in Stimulant Self Administration and Addiction.
AB  - Sigma(1) receptors (sigma(1)Rs) represent a structurally unique class of
      intracellular proteins that function as chaperones. sigma(1)Rs translocate from
      the mitochondria-associated membrane to the cell nucleus or cell membrane, and
      through protein-protein interactions influence several targets, including ion
      channels, G-protein-coupled receptors, lipids, and other signaling proteins.
      Several studies have demonstrated that sigmaR antagonists block stimulant-induced
      behavioral effects, including ambulatory activity, sensitization, and acute
      toxicities. Curiously, the effects of stimulants have been blocked by sigmaR
      antagonists tested under place-conditioning but not self-administration
      procedures, indicating fundamental differences in the mechanisms underlying these
      two effects. The self administration of sigmaR agonists has been found in
      subjects previously trained to self administer cocaine. The reinforcing effects
      of the sigmaR agonists were blocked by sigmaR antagonists. Additionally, sigmaR
      agonists were found to increase dopamine concentrations in the nucleus accumbens
      shell, a brain region considered important for the reinforcing effects of abused
      drugs. Although the effects of the sigmaR agonist, DTG, on dopamine were obtained
      at doses that approximated those that maintained self administration behavior
      those of another agonist, PRE-084 required higher doses. The effects of DTG were
      antagonized by non-selective or a preferential sigma(2)R antagonist but not by a
      preferential sigma(1)R antagonist. The effects of PRE-084 on dopamine were
      insensitive to sigmaR antagonists. The data suggest that the self administration
      of sigmaR agonists is independent of dopamine and the findings are discussed in
      light of a hypothesis that cocaine has both intracellular actions mediated by
      sigmaRs, as well as extracellular actions mediated through conventionally studied
      mechanisms. The co-activation and potential interactions among these mechanisms,
      in particular those involving the intracellular chaperone sigmaRs, may lead to
      the pernicious addictive effects of stimulant drugs.

PMID- 21904474
TI  - The Use of ERCP Versus MRCP in Primary Sclerosing Cholangitis.

PMID- 21904475
TI  - Vaccinations and the Utilization of Immunosuppressive IBD Therapy.

PMID- 21904476
TI  - Correlation of Laparoscopic Liver Biopsy to Elasticity Measurements (FibroScan)
      in Patients With Chronic Liver Disease.
AB  - BACKGROUND: Elastography is a noninvasive method to assess liver fibrosis by
      measuring liver stiffness. Studies have compared elas-tography to percutaneous
      biopsy. Laparoscopic biopsy is associated with decreased sampling error compared
      to percutaneous biopsy, as laparoscopic biopsies are obtained from both liver
      lobes and gross nodu-larity can be visualized. METHODS: Patients undergoing
      laparoscopic liver biopsy were enrolled. Gross liver appearance was assessed, and
      biopsy specimens were blindly evaluated by a pathologist. Elastography
      (FibroScan) was used to measure liver stiffness. RESULTS: 101 patients were
      examined. Fibrosis was related to elasticity (Spearman correlation r=0.63;
      P<.0001). Elasticity was strongly associated with advanced stages of fibrosis
      (stages 3 and 4; Spearman correlation r(2)=0.44; P<.001). Significant fibrosis
      was associated with an irregular liver surface, nodularity, and thickened edge
      (multiple regression r(2)=0.41; P<.001). Increased elasticity was associated with
      a fatty-appearing liver, irregular surface, firmness, and nodularity (multiple
      regression r(2)=0.46; P<.001). Receiver operating characteristic curve for
      elasticity for identifying patients with a liver fibrosis stage of at least 3 or
      of 4 had an area under the curve (AUC) of 0.85 or 0.86, respectively. AUC was
      0.857 when gross nodularity was used as the gold standard for cirrhosis and 0.875
      when nodularity/histology were used. Elasticity of at least 7 kPa, at least 9.5
      kPa, and at least 11.8 kPa had the highest accuracy for identifying patients with
      a fibrosis stage of at least 2, at least 3, and 4, respectively. In hepatitis C
      patients, AUC was 0.921, 0.882, and 0.925 when histology, gross nodularity, and
      nodularity/histology, respectively, were used as the gold standard for cirrhosis.
      CONCLUSION: FibroScan could be useful for detecting advanced stages of fibrosis
      when validated against laparoscopic liver biopsy.

PMID- 21904477
TI  - A Case of Type IV Cholecystobiliary Fistula.

PMID- 21904478
TI  - Review.

PMID- 21904480
TI  - A case of new onset Crohn's disease after renal transplantation.

PMID- 21904479
TI  - Crohn's disease and solid organ transplantation.

PMID- 21904482
TI  - Gastro-hep news.

PMID- 21904481
TI  - A new look at a mainstay ulcerative colitis therapy.

PMID- 21904483
TI  - Treatment of older patients with hiatal hernia.

PMID- 21904484
TI  - Sinusoidal obstruction syndrome.

PMID- 21904485
TI  - Update on the use of capsule endoscopy.

PMID- 21904486
TI  - Evolving protocols in colorectal cancer surveillance.

PMID- 21904487
TI  - Highlights from the 2007 ACG.

PMID- 21904488
TI  - Leukocytapheresis in the treatment of nasal Crohn's disease.

PMID- 21904489
TI  - Nasal Crohn's disease /apheresis.

PMID- 21904490
TI  - Current Treatment Options for Severe Clostridium difficile-associated Disease.
AB  - A notable trend toward severe Clostridium difficile colitis and poor outcomes has
      emerged since recognition of the hyper-virulent C. difficile NAP1/027 strain.
      This trend has increased the emphasis on appropriate treatment regimens in
      refractory cases of C. difficile infection. In mild-to-moderate cases, oral
      metronidazole remains adequate first-line therapy, but in the absence of a good
      clinical response, switching to vancomycin may be necessary. Oral vancomycin
      should be used as initial therapy in severely ill patients or patients who cannot
      tolerate metronidazole. Rectal administration of vancomycin may be used as
      adjunctive therapy for severely ill patients. Patients with an ileus who cannot
      tolerate oral medications may improve with adjunct intravenous metronidazole
      and/or rectal vancomycin. Early surgical consultation should be requested, as
      some patients will require emergent colectomy. The shifting landscape of C.
      difficile infection has undermined our complacency regarding this long-recognized
      disease.

PMID- 21904492
TI  - The Role of EUS in the Investigation of Abdominal Pain of Possible Pancreatic
      Origin.

PMID- 21904491
TI  - Pediatric gastrointestinal motility disorders: challenges and a clinical update.
AB  - Pediatric gastrointestinal motility disorders are common and can range from
      relatively benign conditions such as functional constipation to more serious
      disorders such as achalasia, Hirschsprung disease, and intestinal
      pseudoobstruction. Performing and interpreting motility evaluations in children
      presents unique challenges and is complicated by a dearth of control information,
      underlying gastrointestinal developmental maturation, technical challenges (eg,
      catheter size limitations), and patient cooperation. Primary diseases such as
      congenital pseudoobstruction or Hirschsprung disease occur more often in
      children, but as with adults, abnormal motility may be secondary to other
      processes. Diagnostic studies include radiographic studies, manometry, breath
      testing, myoelectrical testing, and histologic evaluation. Although recent
      advances in technology, genetics, and biology are making an important impact and
      have allowed for a better understanding of the pathophysiology and therapy of
      gastrointestinal motility disorders in children, further research and new
      therapeutic agents are needed.

PMID- 21904493
TI  - Polycystic liver disease.

PMID- 21904495
TI  - Gastro-hep news.

PMID- 21904494
TI  - Current surveillance and therapeutic options for barrett esophagus.

PMID- 21904496
TI  - Developing universal electronic medical records.

PMID- 21904497
TI  - The optimization of immunosuppressive and biologic cotherapies in inflammatory
      bowel disease.

PMID- 21904499
TI  - Healing of leg ulcers associated with transjugular intrahepatic portosystemic
      shunt in decompensated cirrhosis: case series of a possible hepatodermal
      syndrome.
AB  - The occurrence of leg ulcers in patients with cirrhosis is not well documented in
      the literature. In this case series, we describe 4 patients with cirrhosis
      complicated by leg ulceration that failed all conventional therapy, yet healed
      completely following the placement of transjugular intrahepatic portosystemic
      shunt. The course of disease and the possibility of a hepatodermal syndrome
      underlying this observation are discussed.

PMID- 21904498
TI  - Screening for hepatocellular carcinoma.
AB  - Hepatocellular carcinoma (HCC) currently has the fifth highest incidence rate
      among tumors worldwide, a rate expected to continue to increase over the next
      several decades. The majority of patients with HCC have cirrhosis of the liver,
      with chronic hepatitis B and C as the major agents of etiology. Despite advances
      in technology, the prognosis of patients with HCC has shown little improvement
      over time, most likely because most patients are diagnosed at advanced stages.
      HCC meets the criteria established by the World Health Organization for
      performing surveillance in those at risk for developing this tumor (ie, patients
      with cirrhosis of the liver). The objective of surveillance is to use a
      relatively simple and inexpensive examination in a large number of individuals to
      determine whether or not they are likely to develop cancer, with the overall goal
      of reducing morbidity and mortality from the cancer. In this article, we evaluate
      the criteria for performing surveillance for HCC and review the data on the
      efficacy of current surveillance programs.

PMID- 21904500
TI  - An Unusual Cause of Profound Weight Loss in a Middle-aged Person.

PMID- 21904501
TI  - Review.

PMID- 21904502
TI  - Premalignant gastric heterotopic pancreas.

PMID- 21904503
TI  - Review.

PMID- 21904504
TI  - Understanding the Mechanism of 5-ASA in Treating Colonic Inflammation.

PMID- 21904505
TI  - Long-term Use of Proton-Pump Inhibitor Therapy.

PMID- 21904506
TI  - Patient-controlled Sedation for Endoscopic Procedures.

PMID- 21904508
TI  - Gastro-hep news.

PMID- 21904507
TI  - Management of elevated serum ferritin levels.

PMID- 21904510
TI  - Intramucosal esophageal dissection leading to esophageal perforation: case report
      and review of the literature.

PMID- 21904511
TI  - Intramural esophageal dissection with perforation.

PMID- 21904512
TI  - Gastro-hep news.

PMID- 21904509
TI  - Diagnosis and treatment of pouchitis.
AB  - Ileal pouch-anal anastomosis following total proctocolectomy has become part of
      the standard surgical treatment for patients with ulcerative colitis or familial
      adenomatous polyposis who require colectomy. Although this surgery has improved
      patient quality of life and significantly reduced the risk of dysplasia or
      neoplasia in ulcerative colitis patients, complications are common. Pouchitis is
      the most common long-term complication of ileal pouch surgery and has a
      significant adverse impact on patient quality of life. The diagnosis and
      differential diagnosis of pouchitis are not straightforward, and the management
      of pouchitis, particularly chronic antibiotic-refractory pouchitis, which is one
      of the leading causes of pouch failures, can be challenging.

PMID- 21904513
TI  - Apoptosis and hepatic necroinflammation.

PMID- 21904515
TI  - News From DDW.

PMID- 21904514
TI  - Double-Balloon Enteroscopy in Patients With Altered Biliary and/or Pancreatic
      Anatomy.

PMID- 21904516
TI  - Emerging Technologies for Esophageal Manometry and pH Monitoring.

PMID- 21904517
TI  - Recent Research in IBD Epidemiology.

PMID- 21904518
TI  - Recent advances in autoimmune pancreatitis.
AB  - ALTHOUGH THE PATHOGENESIS OF AUTOIMMUNE PANCREATITIS REMAINS UNCLEAR, THIS REPORT
      PRESENTS RECENT EVIDENCE OF THE CLINICAL ASPECTS OF THIS DISEASE: mild abdominal
      symptoms, usually without acute attacks of pancreatitis; occasional presence of
      obstructive jaundice; elevated levels of serum gammaglobulin, immunoglobulin
      (Ig)G, or IgG4; presence of autoantibodies; diffuse enlargement of the pancreas;
      irregular narrowing of the pancreatic duct (sclerosing pancreatitis), often with
      intrapancreatic biliary stenosis or coexisting biliary lesions (sclerosing
      cholangitis similar to primary sclerosing cholangitis) seen on endoscopic
      retrograde cholangiopancreatography; fibrotic changes with lymphocyte and IgG4
      positive plasmacyte infiltration and obliterative phlebitis; occasional
      association with other systemic lesions (such as sialadenitis), retroperitoneal
      fibrosis, and interstitial renal tubular disorders; and response to steroid
      therapy. Based upon these findings, several sets of diagnostic criteria have been
      proposed. Further studies and international consensus for diagnostic criteria and
      pathogenetic mechanisms are needed.

PMID- 21904519
TI  - Acute gastric dilatation in a patient with spinal injury and multiple myeloma.

PMID- 21904520
TI  - Review.

PMID- 21904521
TI  - Hepatocellular Carcinoma in Wilson Disease-related Liver Cirrhosis.

PMID- 21904522
TI  - Wilson disease and hepatocellular carcinoma.

PMID- 21904523
TI  - Vascular growth in health and disease.
AB  - Vascular growth forms the first functional organ system during development, and
      continues into adult life, wherein it is often associated with disease states.
      Genetically determined vasculogenesis produces a primary vascular plexus during
      ontogenesis. Angiogenesis, occurring, e.g., in response to metabolic stress
      within hypoxic tissues, enhances tissue capillarization. Arteriogenesis denotes
      the adaptive outgrowth of pre-existent collateral arteries to bypass arterial
      stenoses in response to hemodynamic changes. It has been debated whether
      vasculogenesis occurs in the adult, and whether or not circulating progenitor
      cells structurally contribute to vessel regeneration. Secondly, the major
      determinants of vascular growth - genetic predisposition, metabolic factors
      (hypoxia), and hemodynamics - cannot be assigned in a mutually exclusive fashion
      to vasculogenesis, angiogenesis, and arteriogenesis, respectively; rather,
      mechanisms overlap. Lastly, all three mechanisms of vessel growth seem to
      contribute to physiological embryogenesis as well as adult adaptive
      vascularization as occurs in tumors or to circumvent arterial stenosis. Thus,
      much conceptual and terminological confusion has been created, while therapies
      targeting neovascularization have yielded promising results in the lab, but
      failed randomized studies when taken to the bedside. Therefore, this review
      article aims at providing an exact definition of the mechanisms of vascular
      growth and their contribution to embryonic development as well as adult adaptive
      revascularization. We have been looking for potential reasons for why clinical
      trials have failed, how vitally the application of appropriate methods of
      measuring and assessment influences study outcomes, and how relevant, e.g.,
      results gained in models of vascular occlusive disease may be for antineoplastic
      strategies, advocating a reverse bedside-to-bench approach, which may hopefully
      yield successful approaches to therapeutically targeting vascular growth.

PMID- 21904524
TI  - GSK3 and Alzheimer's Disease: Facts and Fiction....
AB  - The physiological functions and pathological roles of the Glycogen synthase
      kinase-type 3 (GSK3) kinases in peripheral and central systems are diverse and
      complex, and therefore hard to unravel in molecular detail in vivo. Our
      assignment to review and discuss available data to clarify the actual position of
      these kinases in the pathology of Alzheimer's dementia (AD) was both ambitious
      and easy. On the one hand, numerous studies are available in isolated,
      recombinant, or cell-based systems, which have resulted in very diverse data-sets
      that are hardly informative for the brain in vivo. At the other extreme,
      reliable, and relevant models for the role of GSK3 in CNS are rare, if not
      lacking. Moreover, (too) many in vivo studies used Li(+) as "specific" inhibitor
      of GSK3, which is factually not valid because lithium ions are neither specific
      nor potent inhibitors of GSK3 in vivo. More specific pharmacological inhibitors
      of GSK3 have met with considerable problems, and are reviewed by others in this
      issue or elsewhere. We concentrate here on AD-related aspects of GSK3 in brain in
      vivo, mainly studied in transgenic mice and highlight some of the more important
      issues, among many remaining: activation of GSK3 by amyloid, phosphorylation of
      protein tau, effects on or interference with synaptic activity, differentiation
      between both GSK3 isoforms. These relate directly to brain function, and brain
      dysfunction in AD, and are to be resolved if we want to understand the molecular
      pathology of this dreadful disease.

PMID- 21904526
TI  - Parallel optical control of spatiotemporal neuronal spike activity using high
      speed digital light processing.
AB  - Neurons in the mammalian neocortex receive inputs from and communicate back to
      thousands of other neurons, creating complex spatiotemporal activity patterns.
      The experimental investigation of these parallel dynamic interactions has been
      limited due to the technical challenges of monitoring or manipulating neuronal
      activity at that level of complexity. Here we describe a new massively parallel
      photostimulation system that can be used to control action potential firing in in
      vitro brain slices with high spatial and temporal resolution while performing
      extracellular or intracellular electrophysiological measurements. The system uses
      digital light processing technology to generate 2-dimensional (2D) stimulus
      patterns with >780,000 independently controlled photostimulation sites that
      operate at high spatial (5.4 MUm) and temporal (>13 kHz) resolution. Light is
      projected through the quartz-glass bottom of the perfusion chamber providing
      access to a large area (2.76 mm * 2.07 mm) of the slice preparation. This system
      has the unique capability to induce temporally precise action potential firing in
      large groups of neurons distributed over a wide area covering several cortical
      columns. Parallel photostimulation opens up new opportunities for the in vitro
      experimental investigation of spatiotemporal neuronal interactions at a broad
      range of anatomical scales.

PMID- 21904525
TI  - Beyond the dopamine receptor: regulation and roles of serine/threonine protein
      phosphatases.
AB  - Dopamine plays an important modulatory role in the central nervous system,
      helping to control critical aspects of motor function and reward learning.
      Alteration in normal dopaminergic neurotransmission underlies multiple
      neurological diseases including schizophrenia, Huntington's disease, and
      Parkinson's disease. Modulation of dopamine-regulated signaling pathways is also
      important in the addictive actions of most drugs of abuse. Our studies over the
      last 30 years have focused on the molecular actions of dopamine acting on medium
      spiny neurons, the predominant neurons of the neostriatum. Striatum-enriched
      phosphoproteins, particularly dopamine and adenosine 3':5'-monophosphate
      regulated phosphoprotein of 32 kDa (DARPP-32), regulator of calmodulin signaling
      (RCS), and ARPP-16, mediate pleiotropic actions of dopamine. Notably, each of
      these proteins, either directly or indirectly, regulates the activity of one of
      the three major subclasses of serine/threonine protein phosphatases, PP1, PP2B,
      and PP2A, respectively. For example, phosphorylation of DARPP-32 at Thr34 by
      protein kinase A results in potent inhibition of PP1, leading to potentiation of
      dopaminergic signaling at multiple steps from the dopamine receptor to the
      nucleus. The discovery of DARPP-32 and its emergence as a critical molecular
      integrator of striatal signaling will be discussed, as will more recent studies
      that highlight novel roles for RCS and ARPP-16 in dopamine-regulated striatal
      signaling pathways.

PMID- 21904527
TI  - A Parametric Empirical Bayesian Framework for the EEG/MEG Inverse Problem:
      Generative Models for Multi-Subject and Multi-Modal Integration.
AB  - We review recent methodological developments within a parametric empirical
      Bayesian (PEB) framework for reconstructing intracranial sources of extracranial
      electroencephalographic (EEG) and magnetoencephalographic (MEG) data under linear
      Gaussian assumptions. The PEB framework offers a natural way to integrate
      multiple constraints (spatial priors) on this inverse problem, such as those
      derived from different modalities (e.g., from functional magnetic resonance
      imaging, fMRI) or from multiple replications (e.g., subjects). Using variations
      of the same basic generative model, we illustrate the application of PEB to three
      cases: (1) symmetric integration (fusion) of MEG and EEG; (2) asymmetric
      integration of MEG or EEG with fMRI, and (3) group-optimization of spatial priors
      across subjects. We evaluate these applications on multi-modal data acquired from
      18 subjects, focusing on energy induced by face perception within a time
      frequency window of 100-220 ms, 8-18 Hz. We show the benefits of multi-modal,
      multi-subject integration in terms of the model evidence and the reproducibility
      (over subjects) of cortical responses to faces.

PMID- 21904529
TI  - Change in sympathetic nerve firing pattern associated with dietary weight loss in
      the metabolic syndrome.
AB  - Sympathetic activation in subjects with the metabolic syndrome (MS) plays a role
      in the pathogenesis of cardiovascular disease development. Diet-induced weight
      loss decreases sympathetic outflow. However the mechanisms that account for
      sympathetic inhibition are not known. We sought to provide a detailed description
      of the sympathetic response to diet by analyzing the firing behavior of single
      unit sympathetic nerve fibers. Fourteen subjects (57 +/- 2 years, nine men, five
      females) fulfilling ATP III criteria for the MS underwent a 3-month low calorie
      diet. Metabolic profile, hemodynamic parameters, and multi-unit and single-unit
      muscle sympathetic nerve activity (MSNA, microneurography) were assessed prior to
      and at the end of the diet. Patients' weight dropped from 96 +/- 4 to 88 +/- 3 kg
      (P < 0.001). This was associated with a decrease in systolic and diastolic blood
      pressure (-12 +/- 3 and -5 +/- 2 mmHg, P < 0.05), and in heart rate (-7 +/- 2
      bpm, P < 0.01) and an improvement in all metabolic parameters (fasting glucose: 
      0.302.1 +/- 0.118 mmol/l, total cholesterol: -0.564 +/- 0.164 mmol/l,
      triglycerides: -0.414 +/- 0.137 mmol/l, P < 0.05). Multi-unit MSNA decreased from
      68 +/- 4 to 59 +/- 5 bursts/100 heartbeats (P < 0.05). Single-unit MSNA indicated
      that the firing rate of individual vasoconstrictor fibers decreased from 59 +/-
      10 to 32 +/- 4 spikes/100 heart beats (P < 0.05). The probability of firing
      decreased from 34 +/- 5 to 23 +/- 3% of heartbeats (P < 0.05), and the incidence
      of multiple firing decreased from 14 +/- 4 to 6 +/- 1% of heartbeats (P < 0.05).
      Cardiac and sympathetic baroreflex function were significantly improved (cardiac
      slope: 6.57 +/- 0.69 to 9.57 +/- 1.20 ms.mmHg(-1); sympathetic slope: -3.86 +/-
      0.34 to -5.05 +/- 0.47 bursts/100 heartbeats.mmHg(-1), P < 0.05 for both).
      Hypocaloric diet decreased sympathetic activity and improved hemodynamic and
      metabolic parameters. The sympathoinhibition associated with weight loss involves
      marked changes, not only in the rate but also in the firing pattern of active
      vasoconstrictive fibers.

PMID- 21904530
TI  - Longitudinal analysis of arterial blood pressure and heart rate response to acute
      behavioral stress in rats with type 1 diabetes mellitus and in age-matched
      controls.
AB  - We recorded via telemetry the arterial blood pressure (BP) and heart rate (HR)
      response to classical conditioning following the spontaneous onset of autoimmune
      diabetes in BBDP/Wor rats vs. age-matched, diabetes-resistant control (BBDR/Wor)
      rats. Our purpose was to evaluate the autonomic regulatory responses to an acute
      stress in a diabetic state of up to 12 months duration. The stress was a 15-s
      pulsed tone (CS+) followed by a 0.5-s tail shock. The initial, transient increase
      in BP (i.e., the "first component," or C(1)), known to be derived from an
      orienting response and produced by a sympathetic increase in peripheral
      resistance, was similar in diabetic and control rats through ~9 months of
      diabetes; it was smaller in diabetic rats 10 months after diabetes onset.
      Weakening of the C(1) BP increase in rats that were diabetic for >10 months is
      consistent with the effects of sympathetic neuropathy. A longer-latency, smaller,
      but sustained "second component" (C(2)) conditional increase in BP, that is
      acquired as a rat learns the association between CS+ and the shock, and which
      results from an increase in cardiac output, was smaller in the diabetic vs.
      control rats starting from the first month of diabetes. A concomitant HR slowing
      was also smaller in diabetic rats. The difference in the C(2) BP increase, as
      observed already during the first month of diabetes, is probably secondary to the
      effects of hyperglycemia upon myocardial metabolism and contractile function, but
      it may also result from effects on cognition. The small HR slowing concomitant
      with the C(2) pressor event is probably secondary to differences in baroreflex
      activation or function, though parasympathetic dysfunction may contribute later
      in the duration of diabetes. The nearly immediate deficit after disease onset in
      the C(2) response indicates that diabetes alters BP and HR responses to external
      challenges prior to the development of structural changes in the vasculature or
      autonomic nerves.

PMID- 21904528
TI  - Anticancer targets in the glycolytic metabolism of tumors: a comprehensive
      review.
AB  - CANCER IS A METABOLIC DISEASE AND THE SOLUTION OF TWO METABOLIC EQUATIONS: to
      produce energy with limited resources and to fulfill the biosynthetic needs of
      proliferating cells. Both equations are solved when glycolysis is uncoupled from
      oxidative phosphorylation in the tricarboxylic acid cycle, a process known as the
      glycolytic switch. This review addresses in a comprehensive manner the main
      molecular events accounting for high-rate glycolysis in cancer. It starts from
      modulation of the Pasteur Effect allowing short-term adaptation to hypoxia,
      highlights the key role exerted by the hypoxia-inducible transcription factor HIF
      1 in long-term adaptation to hypoxia, and summarizes the current knowledge
      concerning the necessary involvement of aerobic glycolysis (the Warburg effect)
      in cancer cell proliferation. Based on the many observations positioning
      glycolysis as a central player in malignancy, the most advanced anticancer
      treatments targeting tumor glycolysis are briefly reviewed.

PMID- 21904531
TI  - Oxytocin Receptor (OXTR) Polymorphisms and Attachment in Human Infants.
AB  - Ordinary variations in human infants' attachment behaviors - their proclivity to
      seek and accept comfort from caregivers - are associated with a wide range of
      individual differences in psychological functioning in adults. The current
      investigation examined variation in the oxytocin receptor (OXTR) gene as one
      possible source of these variations in infant attachment. One hundred seventy-six
      infants (77 Caucasian, 99 non-Caucasian) were classified as securely or
      insecurely attached based on their behavior in the Strange Situation (Ainsworth
      et al., 1978). The A allele of OXTR rs2254298 was associated with attachment
      security in the non-Caucasian infants (p < 0.005). These findings underscore the
      importance of oxytocin in the development of human social behavior and support
      its role in social stress-regulation and the development of trust.

PMID- 21904532
TI  - The psychophysics of brain rhythms.
AB  - It is becoming increasingly apparent that brain oscillations in various frequency
      bands play important roles in perceptual and attentional processes.
      Understandably, most of the associated experimental evidence comes from human or
      animal electrophysiological studies, allowing direct access to the oscillatory
      activities. However, such periodicities in perception and attention should, in
      theory, also be observable using the proper psychophysical tools. Here, we review
      a number of psychophysical techniques that have been used by us and other
      authors, in successful and sometimes unsuccessful attempts, to reveal the
      rhythmic nature of perceptual and attentional processes. We argue that the two
      existing and largely distinct debates about discrete vs. continuous perception
      and parallel vs. sequential attention should in fact be regarded as two facets of
      the same question: how do brain rhythms shape the psychological operations of
      perception and attention?

PMID- 21904533
TI  - Multi-modal MRI analysis with disease-specific spatial filtering: initial testing
      to predict mild cognitive impairment patients who convert to Alzheimer's disease.
AB  - BACKGROUND: Alterations of the gray and white matter have been identified in
      Alzheimer's disease (AD) by structural magnetic resonance imaging (MRI) and
      diffusion tensor imaging (DTI). However, whether the combination of these
      modalities could increase the diagnostic performance is unknown. METHODS:
      Participants included 19 AD patients, 22 amnestic mild cognitive impairment
      (aMCI) patients, and 22 cognitively normal elderly (NC). The aMCI group was
      further divided into an "aMCI-converter" group (converted to AD dementia within 3
      years), and an "aMCI-stable" group who did not convert in this time period. A
      T(1)-weighted image, a T(2) map, and a DTI of each participant were normalized,
      and voxel-based comparisons between AD and NC groups were performed. Regions-of
      interest, which defined the areas with significant differences between AD and NC,
      were created for each modality and named "disease-specific spatial filters"
      (DSF). Linear discriminant analysis was used to optimize the combination of
      multiple MRI measurements extracted by DSF to effectively differentiate AD from
      NC. The resultant DSF and the discriminant function were applied to the aMCI
      group to investigate the power to differentiate the aMCI-converters from the aMCI
      stable patients. RESULTS: The multi-modal approach with AD-specific filters led
      to a predictive model with an area under the receiver operating characteristic
      curve (AUC) of 0.93, in differentiating aMCI-converters from aMCI-stable
      patients. This AUC was better than that of a single-contrast-based approach, such
      as T(1)-based morphometry or diffusion anisotropy analysis. CONCLUSION: The multi
      modal approach has the potential to increase the value of MRI in predicting
      conversion from aMCI to AD.

PMID- 21904534
TI  - Modulation of Mucosal Immune Response, Tolerance, and Proliferation in Mice
      Colonized by the Mucin-Degrader Akkermansia muciniphila.
AB  - Epithelial cells of the mammalian intestine are covered with a mucus layer that
      prevents direct contact with intestinal microbes but also constitutes a substrate
      for mucus-degrading bacteria. To study the effect of mucus degradation on the
      host response, germ-free mice were colonized with Akkermansia muciniphila. This
      anaerobic bacterium belonging to the Verrucomicrobia is specialized in the
      degradation of mucin, the glycoprotein present in mucus, and found in high
      numbers in the intestinal tract of human and other mammalian species. Efficient
      colonization of A. muciniphila was observed with highest numbers in the cecum,
      where most mucin is produced. In contrast, following colonization by
      Lactobacillus plantarum, a facultative anaerobe belonging to the Firmicutes that
      ferments carbohydrates, similar cell-numbers were found at all intestinal sites.
      Whereas A. muciniphila was located closely associated with the intestinal cells,
      L. plantarum was exclusively found in the lumen. The global transcriptional host
      response was determined in intestinal biopsies and revealed a consistent, site
      specific, and unique modulation of about 750 genes in mice colonized by A.
      muciniphila and over 1500 genes after colonization by L. plantarum. Pathway
      reconstructions showed that colonization by A. muciniphila altered mucosal gene
      expression profiles toward increased expression of genes involved in immune
      responses and cell fate determination, while colonization by L. plantarum led to
      up-regulation of lipid metabolism. These indicate that the colonizers induce host
      responses that are specific per intestinal location. In conclusion, we propose
      that A. muciniphila modulates pathways involved in establishing homeostasis for
      basal metabolism and immune tolerance toward commensal microbiota.

PMID- 21904535
TI  - In vivo Bioluminescence Imaging of Burkholderia mallei Respiratory Infection and
      Treatment in the Mouse Model.
AB  - Bioluminescent imaging (BLI) technology is a powerful tool for monitoring
      infectious disease progression and treatment approaches. BLI is particularly
      useful for tracking fastidious intracellular pathogens that might be difficult to
      recover from certain organs. Burkholderia mallei, the causative agent of
      glanders, is a facultative intracellular pathogen and has been classified by the
      CDC as a Category B select agent due to its highly infectious nature and
      potential use as a biological weapon. Very little is known regarding pathogenesis
      or treatment of glanders. We investigated the use of bioluminescent reporter
      constructs to monitor the dynamics of infection as well as the efficacy of
      therapeutics for B. mallei in real-time. A stable luminescent reporter B. mallei
      strain was created using the pUTmini-Tn5::luxKm2 plasmid and used to monitor
      glanders in the BALB/c murine model. Mice were infected via the intranasal route
      with 5 * 10(3) bacteria and monitored by BLI at 24, 48, and 72 h. We verified
      that our reporter construct maintained similar virulence and growth kinetics
      compared to wild-type B. mallei and confirmed that it maintains luminescent
      stability in the presence or absence of antibiotic selection. The luminescent
      signal was initially seen in the lungs, and progressed to the liver and spleen
      over the course of infection. We demonstrated that antibiotic treatment 24 h post
      infection resulted in reduction of bioluminescence that can be attributed to
      decreased bacterial burden in target organs. These findings suggest that BLI can
      be used to monitor disease progression and efficacy of therapeutics during
      glanders infections. Finally, we report an alternative method to mini-Tn5::luxKm2
      transposon using mini-Tn7-lux elements that insert site-specifically at known
      genomic attachment sites and that can also be used to tag bacteria.

PMID- 21904537
TI  - Mycobacterium tuberculosis response to stress from reactive oxygen and nitrogen
      species.

PMID- 21904536
TI  - Pathology of Kaposi's Sarcoma-Associated Herpesvirus Infection.
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV; human herpesvirus 8) is a human
      herpesvirus, classified as a gamma-herpesvirus. KSHV is detected in Kaposi's
      sarcoma (KS), primary effusion lymphoma (PEL), and some cases of multicentric
      Castleman's disease (MCD). Similar to other herpes viruses, there are two phases
      of infection, latent and lytic. In KSHV-associated malignancies such as KS and
      PEL, KSHV latently infects almost all tumor cells. Quantitative PCR analysis
      revealed that each tumor cell contains one copy of KSHV in KS lesions. The
      oncogenesis by KSHV has remained unclear. Latency-associated nuclear antigen
      (LANA)-1 plays an important role in the pathogenesis of KSHV-associated
      malignancies through inhibition of apoptosis and maintenance of latency. Because
      all KSHV-infected cells express LANA-1, LANA-1 immunohistochemistry is a useful
      tool for diagnosis of KSHV infection. KSHV encodes some homologs of cellular
      proteins including cell-cycle regulators, cytokines, and chemokines, such as
      cyclin D, G-protein-coupled protein, interleukin-6, and macrophage inflammatory
      protein-1 and -2. These viral proteins mimic or disrupt host cytokine signals,
      resulting in microenvironments amenable to tumor growth. Lytic infection is
      frequently seen in MCD tissues, suggesting a different pathogenesis from KS and
      lymphoma.

PMID- 21904538
TI  - Deconvolution-Based CT and MR Brain Perfusion Measurement: Theoretical Model
      Revisited and Practical Implementation Details.
AB  - Deconvolution-based analysis of CT and MR brain perfusion data is widely used in
      clinical practice and it is still a topic of ongoing research activities. In this
      paper, we present a comprehensive derivation and explanation of the underlying
      physiological model for intravascular tracer systems. We also discuss practical
      details that are needed to properly implement algorithms for perfusion analysis.
      Our description of the practical computer implementation is focused on the most
      frequently employed algebraic deconvolution methods based on the singular value
      decomposition. In particular, we further discuss the need for regularization in
      order to obtain physiologically reasonable results. We include an overview of
      relevant preprocessing steps and provide numerous references to the literature.
      We cover both CT and MR brain perfusion imaging in this paper because they share
      many common aspects. The combination of both the theoretical as well as the
      practical aspects of perfusion analysis explicitly emphasizes the simplifications
      to the underlying physiological model that are necessary in order to apply it to
      measured data acquired with current CT and MR scanners.

PMID- 21904539
TI  - Cardiomyocyte-Restricted Deletion of PPARbeta/delta in PPARalpha-Null Mice Causes
      Impaired Mitochondrial Biogenesis and Defense, but No Further Depression of
      Myocardial Fatty Acid Oxidation.
AB  - It is well documented that PPARalpha and PPARbeta/delta share overlapping
      functions in regulating myocardial lipid metabolism. However, previous studies
      demonstrated that cardiomyocyte-restricted PPARbeta/delta deficiency in mice
      leads to severe cardiac pathological development, whereas global PPARalpha
      knockout shows a benign cardiac phenotype. It is unknown whether a PPARalpha-null
      background would alter the pathological development in mice with cardiomyocyte
      restricted PPARbeta/delta deficiency. In the present study, a mouse model with
      long-term PPARbeta/delta deficiency in PPARalpha-null background showed a
      comparably reduced cardiac expression of lipid metabolism to those of single PPAR
      deficient mouse models. The PPARalpha-null background did not rescue or aggravate
      the cardiac pathological development linked to cardiomyocyte-restricted
      PPARbeta/delta deficiency. Moreover, PPARalpha-null did not alter the phenotypic
      development in adult mice with the short-term deletion of PPARbeta/delta in their
      hearts, which showed mitochondrial abnormalities, depressed cardiac performance,
      and cardiac hypertrophy with attenuated expression of key factors in
      mitochondrial biogenesis and defense. The present study demonstrates that
      cardiomyocyte-restricted deletion of PPARbeta/delta in PPARalpha-null mice causes
      impaired mitochondrial biogenesis and defense, but no further depression of fatty
      acid oxidation. Therefore, PPARbeta/delta is essential for maintaining
      mitochondrial biogenesis and defense in cardiomyocytes independent of PPARalpha.

PMID- 21904540
TI  - Effect of exposure of human monocyte-derived macrophages to high, versus normal,
      glucose on subsequent lipid accumulation from glycated and acetylated low-density
      lipoproteins.
AB  - During atherosclerosis monocyte-derived macrophages accumulate cholesteryl esters
      from low-density lipoproteins (LDLs) via lectin-like oxidised LDL receptor-1 (LOX
      1) and class AI and AII (SR-AI, SR-AII) and class B (SR-BI, CD36) scavenger
      receptors. Here we examined the hypothesis that hyperglycaemia may modulate
      receptor expression and hence lipid accumulation in macrophages. Human monocytes
      were matured into macrophages in 30 versus 5 mM glucose and receptor expression
      and lipid accumulation quantified. High glucose elevated LOX1 mRNA, but decreased
      SR-AI, SR-BI, LDLR, and CD36 mRNA. SR-BI and CD36 protein levels were decreased.
      Normo- and hyperglycaemic cells accumulated cholesteryl esters from modified LDL
      to a greater extent than control LDL, but total and individual cholesteryl ester
      accumulation was not affected by glucose levels. It is concluded that, whilst
      macrophage scavenger receptor mRNA and protein levels can be modulated by high
      glucose, these are not key factors in lipid accumulation by human macrophages
      under the conditions examined.

PMID- 21904541
TI  - Expression of endoplasmic reticulum stress-related factors in the retinas of
      diabetic rats.
AB  - Recent reports show that ER stress plays an important role in diabetic
      retinopathy (DR), but ER stress is a complicated process involving a network of
      signaling pathways and hundreds of factors, What factors involved in DR are not
      yet understood. We selected 89 ER stress factors from more than 200, A rat
      diabetes model was established by intraperitoneal injection of streptozotocin
      (STZ). The expression of 89 ER stress-related factors was found in the retinas of
      diabetic rats, at both 1- and 3-months after development of diabetes, by
      quantitative real-time polymerase chain reaction arrays. There were significant
      changes in expression levels of 13 and 12 ER stress-related factors in the
      diabetic rat retinas in the first and third month after the development of
      diabetes, Based on the array results, homocysteine- inducible, endoplasmic
      reticulum stress-inducible, ubiquitin-like domain member 1(HERP), and
      synoviolin(HRD1) were studied further by immunofluorescence and Western blot.
      Immunofluorescence and Western blot analyses showed that the expression of HERP
      was reduced in the retinas of diabetic rats in first and third month. The
      expression of Hrd1 did not change significantly in the retinas of diabetic rats
      in the first month but was reduced in the third month.

PMID- 21904542
TI  - Accelerometry-based classification of human activities using Markov modeling.
AB  - Accelerometers are a popular choice as body-motion sensors: the reason is partly
      in their capability of extracting information that is useful for automatically
      inferring the physical activity in which the human subject is involved, beside
      their role in feeding biomechanical parameters estimators. Automatic
      classification of human physical activities is highly attractive for pervasive
      computing systems, whereas contextual awareness may ease the human-machine
      interaction, and in biomedicine, whereas wearable sensor systems are proposed for
      long-term monitoring. This paper is concerned with the machine learning
      algorithms needed to perform the classification task. Hidden Markov Model (HMM)
      classifiers are studied by contrasting them with Gaussian Mixture Model (GMM)
      classifiers. HMMs incorporate the statistical information available on movement
      dynamics into the classification process, without discarding the time history of
      previous outcomes as GMMs do. An example of the benefits of the obtained
      statistical leverage is illustrated and discussed by analyzing two datasets of
      accelerometer time series.

PMID- 21904543
TI  - Functional magnetic resonance in the evaluation of oesophageal motility
      disorders.
AB  - Functional magnetic resonance imaging (fMRI) has been recently proposed for the
      evaluation of the esophagus. Our aim is to assess the role of fMRI as a technique
      to assess morphological and functional parameters of the esophagus in patients
      with esophageal motor disorders and in healthy controls. Subsequently, we
      assessed the diagnostic efficiency of fMRI in comparison to videofluoroscopic and
      manometric findings in the investigation of patients with esophageal motor
      disorders. Considering that fMRI was shown to offer valuable information on bolus
      transit and on the caliber of the esophagus, variations of these two parameters
      in the different types of esophageal motor alterations have been assessed. fMRI,
      compared to manometry and videofluoroscopy, showed that a deranged or absent
      peristalsis is significantly associated with slower transit time and with
      increased esophageal diameter. Although further studies are needed, fMRI
      represents a promising noninvasive technique for the integrated functional and
      morphological evaluation of esophageal motility disorders.

PMID- 21904544
TI  - Pelvic lymphadenectomy in the treatment of invasive bladder cancer: literature
      review.
AB  - The standard surgical treatment of invasive bladder cancer is the radical
      cystectomy and pelvic lymph node dissection (PLND). Up to one-third of patients
      with invasive bladder cancer have lymph node metastasis. Thus, PLND has important
      therapeutic and prognostic benefits. The number of lymph nodes that should be
      removed and the extent of the PLND are still a controversial issue. Recently, the
      trend of PLND increased toward more extended PLND. Several prognostic factors
      related to PLND were reported in the literature. In this paper, we will discuss
      the different PLND templates, number of lymph nodes that should be resected,
      lymph node density, lymphovascular invasion, tumor burden, extracapsular
      extension, and the aggregate lymph node metastasis diameter.

PMID- 21904546
TI  - Genome evolution.

PMID- 21904545
TI  - Immune Modulation as Adjunctive Therapy for Pneumocystis pneumonia.
AB  - Pneumocystis is an opportunistic fungal respiratory pathogen that causes life
      threatening pneumonia (Pcp) in patients suffering from defects in cell-mediated
      immunity, including those with acquired immunodeficiency syndrome (AIDS) and
      immunosuppression secondary to chemotherapy or organ transplantation. Despite
      major advances in health care, the mortality associated with Pcp has changed
      little over the past 25  years. Pcp remains a leading cause of death among HIV
      infected patients, with mortality rates of 50% or higher for patients developing
      severe Pcp. In addition, as more potent immunosuppressive therapies are developed
      for chronic inflammatory diseases, more cases of Pcp are occurring in non-HIV
      patients and in previously unreported clinical settings. These features highlight
      the importance of developing a better understanding of the pathogenesis of this
      disease, and the need to search for new therapeutic strategies to improve the
      outcome of Pcp patients. Immune-mediated inflammatory responses play an important
      role in the pathogenesis of Pcp, and may be even more significant in determining
      the outcome of Pcp than direct damage due to the organism itself. In this review
      we will summarize the immunopathogenic mechanisms that contribute to Pcp
      associated lung injury, and discuss the potential to target these pathways for
      adjunctive immune modulation therapy for Pcp.

PMID- 21904547
TI  - Moderate weight reduction in an outpatient obesity intervention program
      significantly reduces insulin resistance and risk factors for cardiovascular
      disease in severely obese adolescents.
AB  - Background. Metabolic risk factors like insulin resistance and dyslipidemia are
      frequently observed in severly obese children. We investigated the hypothesis
      that moderate weight reduction by a low-threshold intervention is already able to
      reduce insulin resistance and cardiovascular risk factors in severely obese
      children. Methods. A group of 58 severely obese children and adolescents between
      8 and 17 years participating in a six-month-long outpatient program was studied
      before and after treatment. The program included behavioral treatment, dietary
      education and specific physical training. Metabolic parameters were measured in
      the fasting state, insulin resistance was evaluated in an oral glucose tolerance
      test. Results. Mean standard deviation score of the body mass index (SDS-BMI) in
      the study group dropped significantly from +2.5 +/- 0.5 to 2.3 +/- 0.6 (P <
      0.0001) after participation in the program. A significant decrease was observed
      in HOMA (6.3 +/- 4.2 versus 4.9 +/- 2.4, P < 0.03, and in peak insulin levels
      (232.7 +/- 132.4 versus 179.2 +/- 73.3 MUU/mL, P < 0.006). Significant reductions
      were also observed in mean levels of hemoglobin A(1c), total cholesterol and LDL
      cholesterol. Conclusions. These data demonstrate that already moderate weight
      reduction is able to decrease insulin resistance and dyslipidemia in severely
      obese children and adolescents.

PMID- 21904548
TI  - Prevalence of epithelial ovarian cancer stem cells correlates with recurrence in
      early-stage ovarian cancer.
AB  - Epithelial ovarian cancer stem cells (EOC stem cells) have been associated with
      recurrence and chemoresistance. CD44 and CK18 are highly expressed in cancer stem
      cells and function as tools for their identification and characterization. We
      investigated the association between the number of CD44+ EOC stem cells in
      ovarian cancer tumors and progression-free survival. EOC stem cells exist as
      clusters located close to the stroma forming the cancer stem cell "niche". 17.1%
      of the samples reveled high number of CD44+ EOC stem cells (>20% positive cells).
      In addition, the number of CD44+ EOC stem cells was significantly higher in
      patients with early-stage ovarian cancer (FIGO I/II), and it was associated with
      shorter progression-free survival (P = 0.026). This study suggests that
      quantification of the number of EOC stem cells in the tumor can be used as a
      predictor of disease and could be applied for treatment selection in early-stage
      ovarian cancer.

PMID- 21904549
TI  - Angiogenesis in acute myeloid leukemia and opportunities for novel therapies.
AB  - Acute myeloid leukemia (AML) arises from neoplastic transformation of
      hematopoietic stem and progenitor cells, and relapsed disease remains one of the
      greater challenges in treating this hematologic malignancy. This paper focuses on
      angiogenic aspects of AML including the significance and prognostic value of bone
      marrow microvessel density and circulating cytokine levels. We show three general
      mechanisms whereby AML exploits angiogenic pathways, including direct induction
      of angiogenesis, paracrine regulation, and autocrine stimulation. We also present
      early evidence that leukemia cells contribute directly to vascular endothelia.
      Novel treatment strategies are proposed, and a review of relevant antiangiogenic
      clinical trials is presented. By understanding how blood vessels can serve as a
      reservoir for refractory and relapsed AML, new diagnostics and promising
      treatment strategies can be developed.

PMID- 21904551
TI  - Oral health-related quality of life of greek adults: a cross-sectional study.
AB  - Purpose. The aim of the present study was to investigate the impact of oral
      health status on the quality of life of adults in different regions of Greece,
      using the Oral Health Impact Profile-short form (OHIP-14). Methods. A random
      sample consisting of a total of 504 Greek adults between the ages of 35-44 years
      (mean 39.1 +/- 3.5) was selected from different urban and rural areas, and face
      to-face interviews were conducted using the validated Greek language OHIP-14.
      Associations of the total OHIP-14 score and its 7 sub-scales along with the self
      perceived quality of life were evaluated with Spearman's correlations. Results.
      The subjects had an overall weighted OHIP-14 score of 1.1 (sd 1.9). No
      significant differences were found for either rural or non-metropolitan areas
      when compared to urban or metropolitan regions. High scores of above 2 were
      determined for functional limitation, physical pain, handicap, and the
      psychological discomfort scales. The education level of the subjects had a
      significant positive impact on the quality of life of the subjects. Conclusions.
      Dental and oral health conditions are factors that do impact on the quality of
      life of individuals.

PMID- 21904550
TI  - The Role of PTEN in Tumor Angiogenesis.
AB  - During the past 20 years, the phosphatase and tensin homolog PTEN has been shown
      to be involved in major physiological processes, and its mutation or loss is
      often associated with tumor formation. In addition PTEN regulates angiogenesis
      not only through its antagonizing effect on the PI3 kinase pathway mainly, but
      also through some phosphatase-independent functions. In this paper we delineate
      the role of this powerful tumor suppressor in tumor angiogenesis and dissect the
      underlying molecular mechanisms. Furthermore, it appears that, in a number of
      cancers, the PTEN status determines the response to chemotherapy, highlighting
      the need to monitor PTEN expression and to develop PTEN-targeted therapies.

PMID- 21904552
TI  - Insights into the Function of the Unstructured N-Terminal Domain of Proteins 4.1R
      and 4.1G in Erythropoiesis.
AB  - Membrane skeletal protein 4.1R is the prototypical member of a family of four
      highly paralogous proteins that include 4.1G, 4.1N, and 4.1B. Two isoforms of
      4.1R (4.1R(135) and 4.1R(80)), as well as 4.1G, are expressed in erythroblasts
      during terminal differentiation, but only 4.1R(80) is present in mature
      erythrocytes. One goal in the field is to better understand the complex
      regulation of cell type and isoform-specific expression of 4.1 proteins. To start
      answering these questions, we are studying in depth the important functions of
      4.1 proteins in the organization and function of the membrane skeleton in
      erythrocytes. We have previously reported that the binding profiles of 4.1R(80)
      and 4.1R(135) to membrane proteins and calmodulin are very different despite the
      similar structure of the membrane-binding domain of 4.1G and 4.1R(135). We have
      accumulated evidence for those differences being caused by the N-terminal 209
      amino acids headpiece region (HP). Interestingly, the HP region is an
      unstructured domain. Here we present an overview of the differences and
      similarities between 4.1 isoforms and paralogs. We also discuss the biological
      significance of unstructured domains.

PMID- 21904553
TI  - Candida albicans versus Candida dubliniensis: Why Is C. albicans More Pathogenic?
AB  - Candida albicans and Candida dubliniensis are highly related pathogenic yeast
      species. However, C. albicans is far more prevalent in human infection and has
      been shown to be more pathogenic in a wide range of infection models. Comparison
      of the genomes of the two species has revealed that they are very similar
      although there are some significant differences, largely due to the expansion of
      virulence-related gene families (e.g., ALS and SAP) in C. albicans, and increased
      levels of pseudogenisation in C. dubliniensis. Comparative global gene expression
      analyses have also been used to investigate differences in the ability of the two
      species to tolerate environmental stress and to produce hyphae, two traits that
      are likely to play a role in the lower virulence of C. dubliniensis. Taken
      together, these data suggest that C. dubliniensis is in the process of undergoing
      reductive evolution and may have become adapted for growth in a specialized
      anatomic niche.

PMID- 21904554
TI  - Communication, psychosocial, and educational outcomes of children with cochlear
      implants and challenges remaining for professionals and parents.
AB  - This paper provides an overview and a synthesis of the findings of a large,
      multifaceted study investigating outcomes from paediatric cochlear implantation.
      The study included children implanted at several Australian implant clinics and
      attending a variety of early intervention and educational settings across a range
      of locations in eastern Australia. It investigated three major aspects of
      childhood cochlear implantation: (1) parental expectations of their children's
      implantation, (2) families' decision-making processes, and (3) the communication,
      social, and educational outcomes of cochlear implantation for deaf children. It
      employed a mixed-methods approach in which quantitative survey data were gathered
      from 247 parents and 151 teachers, and qualitative data from semistructured
      interviews with 27 parents, 15 teachers, and 11 children and adolescents with
      cochlear implants. The summarised findings highlight several areas where
      challenges remain for implant clinics, parents, and educators if children with
      cochlear implants are to reach their full potential personally, educationally,
      and socially.

PMID- 21904555
TI  - Clinicopathological Role of Serum-Derived Hyaluronan-Associated Protein (SHAP)
      Hyaluronan Complex in Endometrial Cancer.
AB  - The role of hyaluronan (HA), serum-derived HA-associated protein (SHAP)-HA
      complex and hyaluronan synthase (HAS) in endometrial carcinomas was investigated.
      The relationship of metalloproteinase (MMP) and its inhibitor (TIMP) with HA and
      the SHAP-HA complex was also examined. The expression of HAS1 was related to the
      depth of myometrial invasion and lymph-vascular space involvement. The serum
      levels of HA, SHAP-HA complex, MMP-9, and TIMP-1 were increased in related with
      the depth of myometrial invasion, histological grade and lymph-vascular space
      involvement. They were also higher in the HAS1-positive group compared to 
      negative group. The serum concentrations of HA and SHAP-HA complex had a
      significant correlation with the MMP-9 and TIMP-1. The patients with elevated
      SHAP-HA complex had the shorter disease-free survival. The multivariate analysis
      revealed that the SHAP-HA complex was the independent variable for disease-free
      survival of endometrial cancer patients. In conclusion, the elevation of serum
      SHAP-HA complex depended on the HAS1 expression and the SHAP-HA complex is a
      useful marker to predict disease recurrence in endometrial cancer patients. The
      SHAP-HA complex may promote the lymph-vascular space involvement and the
      synthesis and activation of MMP-9 and TIMP-1 in the progression of endometrial
      cancer.

PMID- 21904556
TI  - Feasibility of multiple repeat gamma knife radiosurgeries for trigeminal
      neuralgia: a case report and review of the literature.
AB  - Treatment options for trigeminal neuralgia (TN) must be customized for the
      individual patient, and physicians must be aware of the medical, surgical, and
      radiation treatment modalities to prescribe optimal treatment courses for
      specific patients. The following case illustrates the potential for gamma knife
      radiosurgery (GKRS) to be repeated multiple times for the purpose of achieving
      facial pain control in cases of TN that have been refractory to other medical and
      surgical options, as well as prior GKRS. The patient described failed to achieve
      pain control with initial GKRS, as well as medical and surgical treatments, but
      experienced significant pain relief for a period of time with a second GKRS
      procedure and later underwent a third procedure. Only a small subset of patients
      have reportedly undergone more than two GKRS for TN; thus, further research and
      long-term clinical followup will be valuable in determining its usefulness in
      specific clinical situations.

PMID- 21904557
TI  - From banking to international governance: fostering innovation in stem cell
      research.
AB  - Stem cell banks are increasingly recognized as an essential resource of
      biological materials for both basic and translational stem cell research. By
      providing transnational access to quality controlled and ethically sourced stem
      cell lines, stem cell banks seek to foster international collaboration and
      innovation. However, given that national stem cell banks operate under different
      policy, regulatory and commercial frameworks, the transnational sharing of stem
      cell materials and data can be complicating. This paper will provide an overview
      of the most pressing challenges regarding the governance of stem cell banks, and
      the difficulties in designing regulatory and commercial frameworks that foster
      stem cell research. Moreover, the paper will shed light on the numerous
      international initiatives that have arisen to help harmonize and standardize stem
      cell banking and research processes to overcome such challenges.

PMID- 21904558
TI  - Structural and Functional Consequences Induced by Post-Translational
      Modifications in alpha-Defensins.
AB  - HNP-1 is an antimicrobial peptide that undergoes proteolytic cleavage to become a
      mature peptide. This process represents the mechanism commonly used by the cells
      to obtain a fully active antimicrobial peptide. In addition, it has been recently
      described that HNP-1 is recognized as substrate by the arginine-specific ADP
      ribosyltransferase-1. Arginine-specific mono-ADP-ribosylation is an enzyme
      catalyzed post-translational modification in which NAD(+) serves as donor of the
      ADP-ribose moiety, which is transferred to the guanidino group of arginines in
      target proteins. While the arginine carries one positive charge, the ADP-ribose
      is negatively charged at the phosphate moieties at physiological pH. Therefore,
      the attachment of one or more ADP-ribose units results in a marked change of
      cationicity. ADP-ribosylation of HNP-1 drastically reduces its cytotoxic and
      antibacterial activities. While the chemotactic activity of HNP-1 remains
      unaltered, its ability to induce interleukin-8 production is enhanced. The
      arginine 14 of HNP-1 modified by the ADP-ribose is in some cases processed into
      ornithine, perhaps representing a different modality in the regulation of HNP-1
      activities.

PMID- 21904559
TI  - Integrated models for solid waste management in tourism regions: Langkawi Island,
      Malaysia.
AB  - The population growth, changing consumption patterns, and rapid urbanization
      contribute significantly to the growing volumes of solid waste that are generated
      in urban settings. As the rate of urbanization increases, demand on the services
      of solid waste management increases. The rapid urban growth in Langkawi Island,
      Malaysia, combined with the increasing rates of solid waste production has
      provided evidence that the traditional solid waste management practices,
      particularly the methods of waste collection and disposal, are inefficient and
      quite nonsustainable. Accordingly, municipal managers and planners in Langkawi
      need to look for and adopt a model for solid waste management that emphasizes an
      efficient and sustainable management of solid wastes in Langkawi Island. This
      study presents the current practices of solid waste management in Langkawi
      Island, describes the composition of the solid waste generated in that area, and
      presents views of local residents and tourist on issues related to solid waste
      management like the aesthetic value of the island environment. The most important
      issue of this paper is that it is the first time that integrated solid waste
      management is investigated in the Langkawi Island.

PMID- 21904560
TI  - Comparative approach to define increased regulatory T cells in different cancer
      subtypes by combined assessment of CD127 and FOXP3.
AB  - In recent years an increase of functional CD4(+)CD25(+) regulatory T cells
      (T(reg) cells) has been established for patients with solid tumors, acute
      leukemias, and lymphomas. We have reported an expanded pool of CD4(+)CD25(high)
      T(reg) cells in patients with chronic lymphatic leukemia (CLL), multiple myeloma
      (MM) as well as its premalignant precursor monoclonal gammopathy of undetermined
      significance (MGUS). In healthy individuals, low-level expression of CD127 on T
      cells in addition to the expression of FOXP3 has been associated with T(reg)
      cells. Here, we demonstrate that the expanded FOXP3(+) T-cell population in
      patients with colorectal cancer, CLL, MGUS, MM, follicular lymphoma, and
      Hodgkin's disease are exclusively CD127(low) T(reg) cells and were strongly
      suppressive. A significant portion of CD127(low)FOXP3(+) T(reg) cells expressed
      only low levels of CD25 suggesting that the previously reported expansion of
      CD25(+) T(reg) cells underestimates the true expansion. The assessment of CCR7
      and CD45RA expression on the expanded CD4(+)CD127(low)FOXP3(+) T(reg) cells
      revealed an increase of both naive as well as central and effector memory T(reg)
      cells in peripheral blood. Our data strongly support superiority of combined
      CD127 and FOXP3 analysis in comparison to CD25 and FOXP3 assessment for further
      quantification of T(reg) cells in malignant diseases.

PMID- 21904561
TI  - Identification and Characterization of Cell Wall Proteins of a Toxic
      Dinoflagellate Alexandrium catenella Using 2-D DIGE and MALDI TOF-TOF Mass
      Spectrometry.
AB  - The cell wall is an important subcellular component of dinoflagellate cells with
      regard to various aspects of cell surface-associated ecophysiology, but the full
      range of cell wall proteins (CWPs) and their functions remain to be elucidated.
      This study identified and characterized CWPs of a toxic dinoflagellate,
      Alexandrium catenella, using a combination of 2D fluorescence difference gel
      electrophoresis (DIGE) and MALDI TOF-TOF mass spectrometry approaches. Using
      sequential extraction and temperature shock methods, sequentially extracted CWPs
      and protoplast proteins, respectively, were separated from A. catenella. From the
      comparison between sequentially extracted CWPs labeled with Cy3 and protoplast
      proteins labeled with Cy5, 120 CWPs were confidently identified in the 2D DIGE
      gel. These proteins gave positive identification of protein orthologues in the
      protein database using de novo sequence analysis and homology-based search. The
      majority of the prominent CWPs identified were hypothetical or putative proteins
      with unknown function or no annotation, while cell wall modification enzymes,
      cell wall structural proteins, transporter/binding proteins, and signaling and
      defense proteins were tentatively identified in agreement with the expected role
      of the extracellular matrix in cell physiology. This work represents the first
      attempt to investigate dinoflagellate CWPs and provides a potential tool for
      future comprehensive characterization of dinoflagellate CWPs and elucidation of
      their physiological functions.

PMID- 21904562
TI  - Effects of bee venom on glutamate-induced toxicity in neuronal and glial cells.
AB  - Bee venom (BV), which is extracted from honeybees, is used in traditional Korean
      medical therapy. Several groups have demonstrated the anti-inflammatory effects
      of BV in osteoarthritis both in vivo and in vitro. Glutamate is the predominant
      excitatory neurotransmitter in the central nervous system (CNS). Changes in
      glutamate release and uptake due to alterations in the activity of glutamate
      transporters have been reported in many neurodegenerative diseases, including
      Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis. To
      assess if BV can prevent glutamate-mediated neurotoxicity, we examined cell
      viability and signal transduction in glutamate-treated neuronal and microglial
      cells in the presence and absence of BV. We induced glutamatergic toxicity in
      neuronal cells and microglial cells and found that BV protected against cell
      death. Furthermore, BV significantly inhibited the cellular toxicity of
      glutamate, and pretreatment with BV altered MAP kinase activation (e.g., JNK,
      ERK, and p38) following exposure to glutamate. These findings suggest that
      treatment with BV may be helpful in reducing glutamatergic cell toxicity in
      neurodegenerative diseases.

PMID- 21904563
TI  - Brain-modulated effects of auricular acupressure on the regulation of autonomic
      function in healthy volunteers.
AB  - Auricular acupuncture has been described in ancient China as well as Egypt,
      Greece, and Rome. At the end of the 1950s, ear acupuncture was further developed
      by the French physician Dr. Paul Nogier. The goal of this study was to develop a
      new system for ear acupressure (vibration stimulation) and to perform pilot
      investigations on the possible acute effects of vibration and manual ear
      acupressure on heart rate (HR), heart rate variability (HRV), pulse wave velocity
      (PWV), and the augmentation index (AIx) using new noninvasive recording methods.
      Investigations were performed in 14 healthy volunteers (mean age +/- SD: 26.3 +/-
      4.3 years; 9 females, 5 males) before, during, and after acupressure vibration
      and manual acupressure stimulation at the "heart" auricular acupuncture point.
      The results showed a significant decrease in HR (P <= 0.001) and a significant
      increase in HRV total (P = 0.008) after manual ear acupressure. The PWV decreased
      markedly (yet insignificantly) whereas the AIx increased immediately after both
      methods of stimulation. The increase in the low-frequency band of HRV was mainly
      based on the intensification of the related mechanism of blood pressure
      regulation (10-s-rhythm). Further studies in Beijing using animal models and
      investigations in Graz using human subjects are already in progress.

PMID- 21904564
TI  - Antirheumatoid Arthritis Activities and Chemical Compositions of Phenolic
      Compounds-Rich Fraction from Urtica atrichocaulis, an Endemic Plant to China.
AB  - Urtica atrichocaulis, an endemic plant to China, is commonly used to treat
      rheumatoid arthritis even though its pharmaceutical activities and chemical
      constituents were not studied. Herein, we reported our investigations on the
      chemical compositions of the phenolic compounds-rich fraction from U.
      atrichocaulis (TFUA) and their antirheumatoid arthritis activities. We found that
      the TFUA significantly inhibited the adjuvant-induced rats arthritis, carrageenin
      induced rats paw edema, cotton pellet-induced mice granuloma, and the acetic acid
      induced mice writhing response. Our phytochemical investigations on the TFUA
      resulted in the first-time isolation and identification of 17 phenolic
      constituents and a bis (5-formylfurfuryl) ether. The extensive HPLC analysis also
      revealed the chemical compositions of TFUA. Our further biological evaluation of
      the main phenolic components, individually and collectively, indicated that the
      antirheumatoid arthritis activities of TFUA were the combined effect of multiple
      phenolic constituents.

PMID- 21904565
TI  - Liuwei dihuang lowers body weight and improves insulin and leptin sensitivity in
      obese rats.
AB  - The present study was aimed at investigating the efficacy and mechanism(s) of
      action of a Chinese herbal formulation, Liuwei Dihuang (LWDH), as a prospective
      natural weight-lowering product. Following a 2-week acclimation period, 48
      obesity-prone (OP-CD) rats were divided into 4 groups (n = 12 each). One group
      served as a positive control for obesity (OP), while the other 3 were challenged
      twice daily by oral gavage with total daily dosages of 500, 1500, or 3500 mg/kg
      BW LWDH, respectively, for 10 weeks. One group (n = 12) of obesity-resistant (OR
      CD) rats served as the normal control group. All rats were fed the same AIN-93G
      diet modified to contain 60% energy from fat. The highest LWDH dose significantly
      reduced body weight during the last 4 weeks of treatment. Food intake was reduced
      beginning in week 2. The high LWDH dose lowered serum triglyceride (TG) and
      nonesterified fatty acid (NEFA) levels and body fat. Both the high and medium
      doses also lowered serum leptin and insulin levels. Liver function testing
      revealed no adverse side effects under the current experimental conditions. The
      results of the present study suggest that LWDH has potential as a preventive or
      therapeutic natural product against overweight and obesity.

PMID- 21904567
TI  - Management of invasive bladder cancer in patients who are not candidates for or
      decline cystectomy.
AB  - Bladder cancer is a common malignancy seen in older adults with coexisting
      medical illnesses. The management of patients with muscle invasive disease
      includes perioperative chemotherapy and radical cystectomy; however, patients may
      decline surgery and older patients with comorbid conditions may not be candidates
      for surgery and thus alternative treatment strategies are needed. Trimodality
      bladder preservation protocols for muscle invasive bladder cancer have generally
      included only those patients who are candidates for a salvage cystectomy. In this
      review, we discuss the current status of bladder preservation treatment options
      for patients with muscle-invasive disease who are not candidates for cystectomy
      or who decline surgery and highlight the need for clinical trials investigating
      novel treatment approaches in this older patient population.

PMID- 21904566
TI  - Total testosterone in young men is more closely associated than free testosterone
      with prostate cancer disparities.
AB  - INTRODUCTION: Early adulthood has been suggested as the most relevant time to
      determine the influence of testosterone on prostate carcinogenesis. For a more
      detailed assessment of this hypothesis, the present study examined whether serum
      total or free testosterone in young men was more closely associated with prostate
      cancer disparities. METHODS: A literature search was conducted for studies that
      reported both total and free testosterone levels for population samples of young
      men, along with prostate cancer incidences for the populations from which study
      populations were sampled. A previously developed analytical method was used to
      standardize the hormone levels of 19 population samples gathered from nine
      studies, and these standardized values were compared with disparities in prostate
      cancer incidence. RESULTS: Population differences in total testosterone levels
      were significantly associated with prostate cancer disparities, r = 0.833, p =
      0.001, as were population differences in free testosterone, r = 0.661, p = 0.027.
      After controlling for age differences, total and free testosterone remained
      associated with prostate cancer disparities, partial r = 0.888, p < 0.001, and
      partial r = 0.657, p = 0.039, respectively. A marginally significant difference
      existed in the strength of relationships between total and free testosterone with
      respect to prostate cancer disparities, with total testosterone exhibiting a
      stronger association, T(2) = 1.573, p = 0.077. CONCLUSIONS: Across analyses,
      total testosterone demonstrated a more robust relationship than free testosterone
      with cancer disparities, which may suggest that total testosterone is the more
      sensitive biomarker for evaluating androgenic stimulation of the prostate gland.

PMID- 21904568
TI  - Instrumentation in endourology.
AB  - Success with endourological procedures requires expertise and instrumentation.
      This review focuses on the instrumentation required for ureteroscopy and
      percutaneous nephrolithotomy, and provides a critical assessment of in vitro and
      clinical studies that have evaluated the comparative effectiveness of these
      medical devices.

PMID- 21904569
TI  - An update on the use of gonadotropin-releasing hormone antagonists in prostate
      cancer.
AB  - Androgen deprivation therapy (ADT) is the main treatment approach in advanced
      prostate cancer and in recent years has primarily involved the use of
      gonadotropin-releasing hormone (GnRH) agonists. However, despite their efficacy,
      GnRH agonists have several drawbacks associated with their mode of action. These
      include an initial testosterone surge and testosterone microsurges on repeat
      administration. GnRH antagonists provide an alternative approach to ADT with a
      more direct mode of action that involves immediate blockade of GnRH receptors.
      Antagonists produce a more rapid suppression of testosterone (and prostate
      specific antigen [PSA]) without a testosterone surge or microsurges and appear to
      offer an effective and well tolerated option for the hormonal treatment of
      prostate cancer. Comparisons with GnRH agonists have shown GnRH antagonists to be
      at least as effective in achieving and maintaining castrate testosterone levels
      in patients with prostate cancer. Furthermore, with antagonists, the lack of an
      initial testosterone surge (which may cause clinical flare) may allow more rapid
      relief of symptoms related to prostate cancer, avoid the need for concomitant
      antiandrogens to prevent clinical flare (so avoiding any antiandrogen-associated
      adverse events) and allow GnRH antagonist use in patients with high tumour burden
      and/or acute problems such as spinal cord compression. Although several
      antagonists have been investigated, only degarelix and abarelix are currently
      available for clinical use in prostate cancer. Currently, degarelix is the most
      extensively studied and widely available agent in this class. Degarelix is one of
      a newer generation of antagonists which, in a comprehensive and ongoing clinical
      development programme, has been shown to provide rapid, profound and sustained
      testosterone suppression without the systemic allergic reactions associated with
      earlier antagonists. This review examines the currently available data on GnRH
      antagonists in prostate cancer.

PMID- 21904570
TI  - Laparoendoscopic single-site pyeloplasty.
AB  - Since the inception of laparoscopic surgery, there has been an ongoing effort to
      develop an even more 'minimally invasive' approach to surgery. A novel example of
      such advancement can be found in laparoendoscopic single-site (LESS) surgery.
      Performing surgery through a single site of access holds the promise of decreased
      morbidity, lower blood loss, shorter convalescence, and improved cosmesis. Given
      the nonextirpative nature of the pyeloplasty procedure, this patient cohort has
      proven to be the ideal candidates for LESS surgery. The driving force behind
      adaptation of this newer technique can be attributed to innovations in access
      sites and devices, instrumentation, optics, and robotic-based assistance. There
      are now several studies in the published literature demonstrating the feasibility
      and efficacy of LESS pyeloplasty in both children and adults. Although
      comparative studies have failed to demonstrate any objective advantage of the
      LESS pyeloplasty operation, it is important to realize that LESS surgery is still
      a fairly new technique. Further technological developments and additional studies
      will ultimately define its role in the field of urologic surgery, and
      subsequently, its application for the pyeloplasty procedure.

PMID- 21904572
TI  - The challenge of developing universal vaccines.
AB  - Antigenic variability of immunodominant antigens is a common mechanism used by
      pathogens to escape the immune response. Frequently, the proposed solution is a
      universal vaccine based on conserved antigens present on all strains of the
      pathogen. Indeed, a lot of progress has been made in the development of vaccines
      that induce broad immune responses. However, truly universal vaccines are not
      easy to produce and still face many challenges, mostly because in those pathogens
      that use antigenic variability to escape the immune response, conserved antigens
      have been selected by evolution to be poorly immunogenic. This review describes
      the progress made towards the development of vaccines inducing broad protection
      against Neisseria meningitidis, influenza, HIV, and Candida and the challenges of
      developing truly universal vaccines.

PMID- 21904571
TI  - Diagnosis and management of premalignant penile lesions.
AB  - Diagnosing premalignant penile lesions from benign penile dermatoses presents a
      unique challenge. The rarity of these conditions and the low incidence of penile
      cancer mean that the majority of our knowledge is based on small, non-randomized,
      retrospective studies. The introduction of specialist penile cancer centres in
      the UK has resulted in the centralization of expertise and resources, and has
      furthered our understanding of the biological behaviour and management of this
      rare malignancy. We review the current trends in the approach to diagnosing and
      treating various premalignant penile conditions.

PMID- 21904573
TI  - Pulmonary lymphangioleiomyomatosis: unusual manifestations of multiple large
      pulmonary nodules with retroperitoneal lymph node involvement mimicking
      metastatic malignancy.
AB  - Pulmonary lymphangioleiomyomatosis (LAM) is a rare, idiopathic disorder that
      predominantly affects the lung parenchyma of women of childbearing age. While the
      characteristic radiographic finding of pulmonary LAM consists of multiple well
      defined thin-walled cysts, we describe a very unusual case of pulmonary LAM with
      multiple bilateral large pulmonary nodules and retroperitoneal involvement
      mimicking metastatic malignancy. A 48-year-old woman who had never smoked with a
      history of bilateral pneumothorax presented with progressive exertional dyspnea
      and abdominal discomfort. Imaging studies revealed multiple enlarged
      retroperitoneal lymph nodes, ascites and bilateral multiple large pulmonary
      nodules ranging from 3 to 18 mm in diameter. Exploratory laparoscopic surgery for
      intra-abdominal lesions and video-assisted thoracoscopic wedge resection of lung
      nodules were carried out to rule out metastatic malignancy. Pathology showed
      benign looking smooth muscle cell proliferation and immunoreactivity for alpha
      smooth muscle actin and HMB-45 in both specimens. After treatment with GnRH
      antagonist, the patient was well over a 6-month period without evidence of
      disease progression.

PMID- 21904574
TI  - Renal infarction and rapidly progressive arterial thromboembolism following a
      percutaneous renal biopsy.
AB  - A percutaneous renal biopsy is the diagnostic procedure of choice in a variety of
      renal diseases. Although the risk is generally minimal, serious complications can
      rarely occur. Here we present the case of a 50-year-old male with renal
      amyloidosis due to myeloma, who suddenly developed left flank pain after a
      percutaneous renal biopsy. Imaging studies revealed a renal infarction with an
      intraluminal thrombus in the left wall of the descending aorta. Subsequent
      arterial thromboembolic events in the left limb followed immediately after the
      femoral arteriography. Arterial thromboembolism is a relatively rare, serious,
      unexpected and multifactorial event that occurs during an exacerbation of the
      nephrotic syndrome. In this case, the arterial vascular trauma from the renal
      biopsy and arterial puncture for angiography might have increased the risk for
      the thrombotic episode that resulted in death. Therefore, a thorough assessment
      for the risk factors prior to an invasive procedure such as a renal biopsy should
      be required so that patients at high risk can be identified.

PMID- 21904577
TI  - Maintenance therapy in advanced non-small cell lung cancer: evolution,
      tolerability and outcomes.
AB  - Non-small cell lung cancer (NSCLC) is the leading cause of cancer death in the
      industrialized world. Despite significant progress in early stage disease,
      survival rates for advanced disease remain low. Maintenance therapy is a
      treatment strategy that has been investigated extensively in NSCLC and has been
      the subject of considerable recent debate. Options for maintenance include
      continuing the initial combination chemotherapy regimen, continuing only single
      agent chemotherapy ('continuation maintenance') or introducing a new agent
      ('switch' maintenance therapy). Therapies that have been studied in this setting
      in randomized trials to date include chemotherapy, molecularly targeted agents
      and immunotherapy approaches. Following the development of multiple new agents
      that show activity in NSCLC, and have a tolerable side-effect profile, there has
      been increasing interest in utilizing them to maintain response to initial
      therapy after treatment with platinum-based doublets. Despite considerable
      controversy, it has become an acceptable treatment paradigm. Here, we briefly
      outline the evolution of this treatment paradigm and examine which subgroups of
      patients are most likely to benefit.

PMID- 21904575
TI  - Genotype-driven therapies for non-small cell lung cancer: focus on EGFR, KRAS and
      ALK gene abnormalities.
AB  - Non-small cell lung cancers (NSCLCs) are heterogeneous cancers. In 2004, the
      identification of epidermal growth factor receptor (EGFR) somatic mutations
      provided the first glimpse of a clinically relevant NSCLC oncogene. Approximately
      70% of NSCLCs with EGFR mutations (exon 19 deletions or the exon 21 L858R) attain
      responses to EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib, with
      improved response rate (RR), progression-free survival (PFS) and in some reports
      overall survival (OS) when compared with EGFR wildtype (WT) cases. Three
      randomized trials of gefitinib versus chemotherapy (IPASS, WJTOG3405, NEJ002) in
      stage IV NSCLC have consistently demonstrated better RR and PFS (hazard ratios of
      0.48 [IPASS], 0.49 [WJTOG3405] and 0.30 [NEJ002]) for EGFR-mutated NSCLCs treated
      with gefitinib. Novel irreversible EGFR TKIs (afatinib, XL647, PF00299804) show
      similar activity in EGFR-mutated patients. A translocation involving the
      anaplastic lymphoma kinase (ALK) gene with EML4, identified in 2007, is the most
      recent oncogene found in NSCLC. Crizotinib (PF02341066), an ALK TKI, has shown
      impressive activity against ALK translocated NSCLC in an expanded cohort of a
      phase I trial (NCT00585195). Over 80 patients have been treated and the RR is
      ~60% with the 6-month PFS rate exceeding 70%. A registration phase III trial of
      crizotinib versus second-line chemotherapy (pemetrexed/docetaxel) is underway
      (PROFILE 1007, NCT00932893). KRAS, EGFR mutations and ALK translocations are
      mutually exclusive and few EGFR WT NSCLCs respond to EGFR TKIs. The promising
      results of EGFR and ALK TKIs in molecular subgroups of NSCLCs herald a new age of
      drug and clinical trial development for patients with NSCLC.

PMID- 21904576
TI  - Prognostic factors in stage III non-small cell lung cancer: a review of
      conventional, metabolic and new biological variables.
AB  - Lung cancer is one of the most frequently occurring neoplasms and usually has a
      poor prognosis because most of the patients present with advanced or metastatic
      disease at the time of diagnosis. Numerous prognostic factors (PFs) have been
      studied, but the two most prominent, having both prognostic and operational
      values, are disease stage and performance status. Even if the literature on PFs
      in lung cancer is impressive, the number of publications specifically dealing
      with PFs in stage III non-small cell lung cancer (NSCLC) is limited. We reviewed
      the literature on this topic and separated the available information into three
      groups: conventional PFs, metabolic criteria (standardized uptake value [SUV]
      measured on(18)F-FDG-PET) and new biomarkers. Performance status and the
      distinction between stage IIIA and IIIB confirmed their prognostic value in stage
      III NSCLC. Other conventional PFs have been suggested such as age, weight loss,
      response to treatment and some characteristics describing the locoregional
      extension of the tumour. There is a place for the SUV as a PF for survival in
      early NSCLC, but its role in stage III NSCLC has to be further assessed. Some new
      biomarkers involved in cell cycle regulation or in apoptosis have been shown to
      have potential value. Their role needs to be confirmed in large prospective
      studies including conventional PFs to determine their independent value as a PF
      in stage III NSCLC. In conclusion, few PFs have been well evaluated in stage III
      NSCLC. New studies, taking into account the modifications derived from the 7th
      international staging system of the UICC, have to be performed.

PMID- 21904578
TI  - Experience of first- and subsequent-line systemic therapy in the treatment of non
      small cell lung cancer.
AB  - INTRODUCTION: The treatment of advanced non-small cell cancer (NSCLC) has changed
      with multiple new treatment algorithms proposed based on histological and
      molecular subtyping but low mutation rates will ensure the dominance of cytotoxic
      chemotherapy. Accordingly, we undertook a detailed review of our practice
      delivering multiple lines of systemic therapy. METHOD: We undertook a
      retrospective review of consecutive patients presenting with advanced (stage
      IIIb/IV) NSCLC treated with systemic therapy at two UK hospitals during a 2-year
      period, January 2007 to December 2008. RESULTS: A total of 130 patients were
      identified, treated with predominantly carboplatin/gemcitabine (20 initially
      radically). Fifty of 110 patients (45%) treated with first-line systemic therapy
      subsequently received second-line therapy, of which 10 patients received third
      line and two patients fourth-line therapy. Sixty three of 110 first-line patients
      (58%) achieved clinical benefit, 19 out of 50 (38%) in the second-line, 6 out of
      10 (60%) in third-line but both patients progressed at fourth-line. Median
      overall survival for 110 patients was 10 months (95% confidence interval [CI] 8.6
      11.4); but 16 months (95% CI 14-17.9) in those receiving multiple lines. Median
      survival from the first cycle of last-line treatment to death in the multiple
      therapy lines was 5 months (95% CI 2.6-7.3) and the majority of patients spent
      more time off treatment. CONCLUSION: Overall our outcomes are consistent with
      published data and show good survival times can be achieved. The future of
      advanced NSCLC is in selecting the best treatment approach on a histological and
      genotypic basis.

PMID- 21904579
TI  - The role of the c-Met pathway in lung cancer and the potential for targeted
      therapy.
AB  - Hepatocyte growth factor receptor (HGFR), the product of the MET gene, plays an
      important role in normal cellular function and oncogenesis. In cancer, HGFR has
      been implicated in cellular proliferation, cell survival, invasion, cell
      motility, metastasis and angiogenesis. Activation of HGFR can occur through
      binding to its ligand, hepatocyte growth factor (HGF),
      overexpression/amplification, mutation, and/or decreased degradation.
      Amplification of HGFR can occur de novo or in resistance to therapy. Mutations of
      HGFR have been described in the tyrosine kinase domain, juxtamembrane domain, or
      semaphorin domain in a number of tumors. These mutations appear to have gain of
      function, and also reflect differential sensitivity to therapeutic inhibition.
      There have been various drugs developed to target HGFR, including antibodies to
      HGFR/HGF, small-molecule inhibitors against the tyrosine kinase domain of HGFR
      and downstream targets. Different HGFR inhibitors are currently in clinical
      trials in lung cancer and a number of solid tumors. Several phase I trials have
      already been completed, and two specific trials have been reported combining HGFR
      with epidermal growth factor receptor (EGFR) inhibition in non-small cell lung
      cancer. In particular, trials involving MetMAb and ARQ197 (tivantinib) have
      gained interest. Ultimately, as individualized therapies become a reality for
      cancers, HGFR will be an important molecular target.

PMID- 21904580
TI  - How close are we to customizing chemotherapy in early non-small cell lung cancer?
AB  - Although surgery is the only potentially curative treatment for early-stage non
      small cell lung cancer (NSCLC), 5-year survival rates range from 77% for stage IA
      tumors to 23% in stage IIIA disease. Adjuvant chemotherapy has recently been
      established as a standard of care for resected stage II-III NSCLC, on the basis
      of large-scale clinical trials employing third-generation platinum-based
      regimens. As the overall absolute 5-year survival benefit from this approach does
      not exceed 5% and potential long-term complications are an issue of concern, the
      aim of customized adjuvant systemic treatment is to optimize the toxicity/benefit
      ratio, so that low-risk individuals are spared from unnecessary intervention,
      while avoiding undertreatment of high-risk patients, including those with stage I
      disease. Therefore, the application of reliable prognostic and predictive
      biomarkers would enable to identify appropriate patients for the most effective
      treatment.This is an overview of the data available on the most promising
      clinicopathological and molecular biomarkers that could affect adjuvant and
      neoadjuvant chemotherapy decisions for operable NSCLC in routine practice. Among
      the numerous candidate molecular biomarkers, only few gene-expression profiling
      signatures provide clinically relevant information warranting further validation.
      On the other hand, real-time quantitative polymerase-chain reaction strategy
      involving relatively small number of genes offers a practical alternative, with
      high cross-platform performance. Although data extrapolation from the metastatic
      setting should be cautious, the concept of personalized, pharmacogenomics-guided
      chemotherapy for early NSCLC seems feasible, and is currently being evaluated in
      randomized phase 2 and 3 trials. The mRNA and/or protein expression levels of
      excision repair cross-complementation group 1, ribonucleotide reductase M1 and
      breast cancer susceptibility gene 1 are among the most potential biomarkers for
      early disease, with stage-independent prognostic and predictive values, the
      clinical utility of which is being validated prospectively. Inter-assay
      discordance in determining the biomarker status and association with clinical
      outcomes is noteworthing.

PMID- 21904581
TI  - Customizing systemic therapy in patients with advanced non-small cell lung
      cancer.
AB  - Lung cancer is the leading cause of cancer deaths worldwide. Standard
      chemotherapy has been shown to improve quality of life and has a modest influence
      on overall survival. This modest improvement in survival is partly due to the
      choice of chemotherapy regimens that have been based on prognostic factors such
      as age, performance status and comorbidities of the patient. This underlines the
      importance of developing a more personalized therapy for patients with non-small
      cell lung cancer. Such an approach may reduce the variation in how individual
      patients respond to medications by tailoring therapies to their genetic profile.
      In this review we focus on several aspects of customized therapy, looking not
      only at patient characteristics but also to tumor histology and specific tumor
      biomarkers.

PMID- 21904582
TI  - Regional differences in the use of hysterectomy.

PMID- 21904583
TI  - Hysterectomy in Germany: a DRG-based nationwide analysis, 2005-2006.
AB  - BACKGROUND: Hysterectomy is among the more common surgical procedures in
      gynecology. The aim of this study was to calculate population-wide rates of
      hysterectomy across Germany and to obtain information on the different modalities
      of hysterectomy currently performed in German hospitals. This was done on the
      basis of nationwide DRG statistics (DRG = diagnosis-related groups) covering the
      years 2005-2006. METHODS: We analyzed the nationwide DRG statistics for 2005 and
      2006, in which we found 305 015 hysterectomies. Based on these data we calculated
      hysterectomy rates for the female population. We determined the indications for
      each hysterectomy with an algorithm based on the ICD-10 codes, and we categorized
      the operations on the basis of their OPS codes (OPS = Operationen- und
      Prozedurenschlussel [Classification of Operations and Procedures]). RESULTS: The
      overall rate of hysterectomy in Germany was 362 per 100 000 person-years. 55% of
      hysterectomies for benign diseases of the female genital tract were performed
      transvaginally. Bilateral ovariectomy was performed concomitantly in 23% of all
      hysterectomies, while 4% of all hysterectomies were subtotal. Hysterectomy rates
      varied considerably across federal states: the rate for benign disease was lowest
      in Hamburg (213.8 per 100 000 women per year) and highest in Mecklenburg-West
      Pomerania (361.9 per 100 000 women per year). CONCLUSION: Hysterectomy rates vary
      markedly from one region to another. Moreover, even though recent studies have
      shown that bilateral ovariectomy is harmful to women under 50 who undergo
      hysterectomy for benign disease, it is still performed in 4% of all
      hysterectomies for benign indications in Germany.

PMID- 21904584
TI  - Concordance analysis: part 16 of a series on evaluation of scientific
      publications.
AB  - BACKGROUND: In this article, we describe qualitative and quantitative methods for
      assessing the degree of agreement (concordance) between two measuring or rating
      techniques. An assessment of concordance is particularly important when a new
      measuring technique is introduced. METHODS: We give an example to illustrate a
      number of simple methods of comparing different measuring or rating techniques,
      and we explain the underlying principle of each method. We also give further
      illustrative examples from medical research papers that were retrieved by a
      selective literature search. RESULTS: Methods of comparing different measuring or
      rating techniques are of two kinds: those with a nominal rating scale and those
      with a continuous rating scale. We only discuss methods for comparing one
      measuring or rating technique with another one. Moreover, we point out some
      common erroneous approaches to concordance analysis. CONCLUSION: Concordance
      analysis is needed to establish the validity of a new diagnostic measuring or
      rating technique or to demonstrate the near-equivalence of multiple measuring or
      rating techniques. Erroneous approaches to concordance analysis can lead to false
      conclusions.

PMID- 21904585
TI  - Ports made from synthetic materials are poorly visible on x-ray films.

PMID- 21904586
TI  - Patient information is lacking.

PMID- 21904587
TI  - Suggested consensus.

PMID- 21904588
TI  - Huber cannula releases silicone particles from port.

PMID- 21904589
TI  - In Reply.

PMID- 21904590
TI  - The treatment of anterior dental trauma.
AB  - BACKGROUND: Avulsed frontal teeth often cannot be saved because of improper or
      lack of initial treatment. The result is a need for multiple interventions over
      the patient's lifetime, which also carry a high financial cost. METHODS: We
      explored the subject of lost anterior teeth in young patients with a PubMed
      search based on the term "prevalence of traumatic dental injuries" over the time
      period 2000-2010. In this article, we selectively review the publications
      retrieved by the search and give case examples to illustrate the proper initial
      treatment of children and adolescents (ages 6 to 17) with broken anterior teeth.
      RESULTS: The search retrieved 138 articles. Here, we review retrospective
      clinical studies of dental trauma between the ages of 6 and 17: only 6 adequately
      designed studies of this type were found. The estimated prevalence of anterior
      dental trauma in this age group ranged from 6.4% to 37.9%. The recommended
      initial steps for the preservation of traumatized teeth are easy to take. Avulsed
      teeth can and should be replanted at once. If there is no time, or if the patient
      simultaneously has other, life-threatening injuries, the avulsed teeth can be
      stored in a special nutrient medium until they can be replanted. Commercially
      available tooth rescue boxes enable replantation to be performed up to 24 hours
      after the injury. CONCLUSION: The authors of the selected studies agree that
      dental trauma is often improperly treated. Timely treatment of injured anterior
      teeth prevents much further damage and expensive treatment for the affected young
      patients.

PMID- 21904591
TI  - The diagnosis and treatment of endometrial cancer: progress and controversies.
AB  - BACKGROUND: Endometrial carcinoma is the fourth most common type of cancer among
      women in Germany, with more than 11 000 newly diagnosed cases each year. The
      present lack of clarity about the optimal clinical management of these patients
      is due in part to inconsistencies in the scientific evidence and in part to
      recent modifications of the FIGO classification. In this article, the issues
      requiring clarification are presented and discussed. METHODS: This article is
      based on a selective review of the pertinent literature, including evidence-based
      guidelines and recommendations. RESULTS AND CONCLUSION: Current scientific
      evidence does not support the screening of asymptomatic women. On the other hand,
      women with postmenopausal and acyclic bleeding should undergo histopathological
      evaluation, particularly if they have risk factors for endometrial cancer. The
      current FIGO classification divides endometrial cancer into stages depending on
      the findings at surgery. On the basis of risk stratification (e.g., by tumor
      stage and histological differentiation grade), women who are judged to be at high
      risk (FIGO Stage IB and above, Grade 3) should undergo not just hysterectomy and
      adnexectomy, but also systematic pelvic and para-aortic lymphadenectomy. Risk
      stratification also determines whether adjuvant radiotherapy should be given. The
      additional or alternative administration of chemotherapy is a particular
      consideration for women at high risk, although the pertinent clinical trials to
      date have yielded conflicting evidence on this point.

PMID- 21904592
TI  - Pancreatic enzyme therapy.
AB  - BACKGROUND: Treatment with pancreatic enzymes must be based on an understanding
      of the normal physiology and pathophysiology of exocrine pancreatic function, as
      well as of the diseases that cause exocrine pancreatic insufficiency of either a
      structural or a functional type. These include chronic pancreatitis, pancreatic
      cancer, cystic fibrosis, pancreaticocibal asynchrony after gastric or pancreatic
      surgery, and celiac disease. METHODS: Selective review of the literature.
      RESULTS: Exocrine pancreatic insufficiency can cause meteorism, diarrhea,
      steatorrhea, and weight loss. All of these manifestations are non-specific except
      steatorrhea. Enzyme supplementation is indicated only for the treatment of
      demonstrated pancreatic dysfunction; unfortunately, however, no sensitive and
      specific pancreatic function tests are currently available. As a result,
      pancreatic enzyme supplementation is considered to be indicated on pragmatic
      grounds when, for example, the patient is suffering from diarrhea and weight loss
      and has been demonstrated to have a disease leading to exocrine pancreatic
      insufficiency. To be acceptable for clinical use, a pancreatin preparation must
      satisfy the following criteria: it must be enterically coated, so that it will
      not be destroyed by gastric acid; mix well with gastric chyme; exit the stomach
      simultaneously with chyme; and be rapidly released from its enteric coating upon
      entering the duodenum. Although there have been no large-scale, randomized
      comparative studies of different types of pancreatin preparation, the current
      clinical preference is for enterically coated micropellets or minitablets with a
      diameter of 2 mm or less. The initial dosage is 20 000 to 40 000 units of lipase
      taken once or twice per meal, with dose adjustment afterward as needed. The dose
      can be raised, and a proton-pump inhibitor can be added on. CONCLUSION: There is
      still no simple test that can be used to diagnose pancreatic exocrine
      insufficiency with certainty. The treatment is symptomatic; its goals are to
      lessen steatorrhea and reverse weight loss.

PMID- 21904593
TI  - Acute treatment with candesartan reduces early injury after permanent middle
      cerebral artery occlusion.
AB  - We have shown that reduction of blood pressure (BP) immediately after the onset
      of reperfusion reduced neurovascular damage and improved functional outcome after
      experimental cerebral ischemia and candesartan is particularly effective in
      improving long-term functional outcome. In this study, we sought to determine if
      early BP lowering with candesartan, in the presence of an occluded cerebral
      artery, will reduce injury and improve outcome after experimental stroke. Male
      Wistar rats underwent 24 h or 7 days of middle cerebral artery occlusion (MCAO).
      A single dose of 1 mg/kg candesartan was administered intravenously at 3 h after
      MCAO. Animals received neurobehavioral testing at 3 h, 24 h, and 7 days, and
      blood pressure was measured by telemetry. Animals had brain tissue collected for
      infarct size (24 h and 7 days), hemoglobin content, matrix metalloproteinase
      (MMP) activity, and vascular endothelial growth factor (VEGF) expression (24 h
      only). Candesartan significantly decreased blood pressure, infarct size (-20%;
      p=0.021), hemoglobin excess (-50%; p=0.0013), and edema (-35%; p=0.0005) at 24 h
      after MCAO. This resulted in a reduced cerebral perfusion deficit (p=0.034) in
      the ischemic hemisphere compared with saline and significantly improved Bederson
      scores and paw grasp. MMP-2, MMP-9, and VEGF were significantly increased by
      MCAO, but there were no differences between candesartan- and saline-treated
      animals. There were no significant differences in behavioral outcome at day 7. BP
      lowering with candesartan reduces early brain injury after experimental stroke
      even when the artery remains occluded. The early benefits were not sustained at 7
      days, as seen in reperfused animals, however. The neuroprotection and
      neurorestorative properties of candesartan may occur by separate distinct
      mechanisms. 

PMID- 21904594
TI  - Antiviral activity of 3(2H)- and 6-chloro-3(2H)-isoflavenes against highly
      diverged, neurovirulent vaccine-derived, type2 poliovirus sewage isolates.
AB  - BACKGROUND: Substituted flavanoids interfere with uncoating of Enteroviruses
      including Sabin-2 polio vaccine strains. However flavanoid resistant and
      dependent, type-2 polio vaccine strains (minimally-diverged), emerged during in
      vitro infections. Between 1998-2009, highly-diverged (8 to >15%) type-2,
      aVDPV(2)s, from two unrelated persistent infections were periodically isolated
      from Israeli sewage. AIM: To determine whether highly evolved aVDPV(2)s derived
      from persistent infections retained sensitivity to isoflavenes. METHODS: Sabin-2
      and ten aVDPV(2) isolates from two independent Israeli sources were titered on
      HEp2C cells in the presence and absence of 3(2H)- Isoflavene and 6-chloro-3(2H)
      Isoflavene. Neurovirulence of nine aVDPV(2)s was measured in PVR-Tg-21 transgenic
      mice. Differences were related to unique amino acid substitutions within capsid
      proteins. PRINCIPAL FINDINGS: The presence of either flavanoid inhibited viral
      titers of Sabin-2 and nine of ten aVDPV(2)s by one to two log(10). The tenth
      aVDPV(2), which had unique amino acid substitution distant from the isoflavene
      binding pocket but clustered at the three- and five-fold axies of symmetry
      between capsomeres, was unaffected by both flavanoids. Genotypic neurovirulence
      attenuation sites in the 5'UTR and VP1 reverted in all aVDPV(2)s and all
      reacquired a full neurovirulent phenotype except one with amino acid
      substitutions flanking the VP1 site. CONCLUSION: Both isoflavenes worked equally
      well against Sabin 2 and most of the highly-diverged, Israeli, aVDPV(2)s
      isolates. Thus, functionality of the hydrophobic pocket may be unaffected by
      selective pressures exerted during persistent poliovirus infections. Amino acid
      substitutions at sites remote from the drug-binding pocket and adjacent to a
      neurovirulence attenuation site may influence flavanoid antiviral activity, and
      neurovirulence, respectively.

PMID- 21904595
TI  - Control of Kaposi's sarcoma-associated herpesvirus reactivation induced by
      multiple signals.
AB  - The ability to control cellular functions can bring about many developments in
      basic biological research and its applications. The presence of multiple signals,
      internal as well as externally imposed, introduces several challenges for
      controlling cellular functions. Additionally the lack of clear understanding of
      the cellular signaling network limits our ability to infer the responses to a
      number of signals. This work investigates the control of Kaposi's sarcoma
      associated herpesvirus reactivation upon treatment with a combination of multiple
      signals. We utilize mathematical model-based as well as experiment-based
      approaches to achieve the desired goals of maximizing virus reactivation. The
      results show that appropriately selected control signals can induce virus lytic
      gene expression about ten folds higher than a single drug; these results were
      validated by comparing the results of the two approaches, and experimentally
      using multiple assays. Additionally, we have quantitatively analyzed potential
      interactions between the used combinations of drugs. Some of these interactions
      were consistent with existing literature, and new interactions emerged and
      warrant further studies. The work presents a general method that can be used to
      quantitatively and systematically study multi-signal induced responses. It
      enables optimization of combinations to achieve desired responses. It also allows
      identifying critical nodes mediating the multi-signal induced responses. The
      concept and the approach used in this work will be directly applicable to other
      diseases such as AIDS and cancer.

PMID- 21904596
TI  - Genetic variation of the human alpha-2-Heremans-Schmid glycoprotein (AHSG) gene
      associated with the risk of SARS-CoV infection.
AB  - Genetic background may play an important role in the process of SARS-CoV
      infection and SARS development. We found several proteins that could interact
      with the nucleocapsid protein of the SARS coronavirus (SARS-CoV). alpha-2
      Heremans-Schmid Glycoprotein (AHSG), which is required for macrophage
      deactivation by endogenous cations, is associated with inflammatory regulation.
      Cytochrome P450 Family 3A (CYP4F3A) is an omega-oxidase that inactivates
      Leukotriene B4 (LTB4) in human neutrophils and the liver. We investigated the
      association between the polymorphisms of these two inflammation-associated genes
      and SARS development. The linkage disequilibrium (LD) maps of these two genes
      were built with Haploview using data on CHB+JPT (version 2) from the HapMap. A
      total of ten tag SNPs were selected and genotyped. In the Guangzhou cohort study,
      after adjusting for age and sex, two AHSG SNPs and one CYP4F3 SNP were found to
      be associated with SARS susceptibility: rs2248690 (adjusted odds ratio [AOR]
      2.42; 95% confidence interval [CI] 1.30-4.51); rs4917 (AOR 1.84; 95% CI 1.02
      3.34); and rs3794987 (AOR 2.01; 95% CI 1.10-3.68). To further validate the
      association, the ten tag SNPs were genotyped in the Beijing cohort. After
      adjusting for age and sex, only rs2248690 (AOR, 1.63; 95% CI, 1.30-2.04) was
      found to be associated with SARS susceptibility. The combined analysis of the two
      studies confirmed tag SNP rs2248690 in AHSG as a susceptibility variant (AOR
      1.70; 95% CI 1.37-2.09). The statistical analysis of the rs2248690 genotype data
      among the patients and healthy controls in the HCW cohort, who were all similarly
      exposed to the SARS virus, also supported the findings. Further, the SNP
      rs2248690 affected the transcriptional activity of the AHSG promoter and thus
      regulated the AHSG serum level. Therefore, our study has demonstrated that the AA
      genotype of rs2268690, which leads to a higher AHSG serum concentration, was
      significantly associated with protection against SARS development.

PMID- 21904597
TI  - Biological activity of CXCL8 forms generated by alternative cleavage of the
      signal peptide or by aminopeptidase-mediated truncation.
AB  - BACKGROUND: Posttranslational modification of chemokines is one of the mechanisms
      that regulate leukocyte migration during inflammation. Multiple natural NH(2)
      terminally truncated forms of the major human neutrophil attractant interleukin-8
      or CXCL8 have been identified. Although differential activity was reported for
      some CXCL8 forms, no biological data are available for others.
      METHODOLOGY/PRINCIPAL FINDINGS: Aminopeptidase-cleaved CXCL8(2-77) and CXCL8(3
      77), the product of alternative cleavage of the signal peptide CXCL8(-2-77) and
      the previously studied forms containing 77 and 72 amino acids, CXCL8(1-77) and
      CXCL8(6-77), were prepared by solid-phase peptide synthesis, purified and folded
      into active proteins. No differences in binding and calcium signaling potency
      were detected between CXCL8(1-77), CXCL8(-2-77), CXCL8(2-77) and CXCL8(3-77) on
      cells transfected with one of the human CXCL8 receptors, i.e. CXCR1 and CXCR2.
      However, CXCL8(-2-77) was more potent compared to CXCL8(1-77), CXCL8(2-77) and
      CXCL8(3-77) in signaling and in vitro chemotaxis of peripheral blood-derived
      human neutrophils. Moreover, CXCL8(-2-77) was less efficiently processed by
      plasmin into the more potent CXCL8(6-77). The truncated forms CXCL8(2-77) and
      CXCL8(3-77) had higher affinity for heparin than CXCL8(1-77), a property
      important for the presentation of CXCL8 on endothelial layers. Upon
      intraperitoneal injection in mice, elongated, truncated and intact CXCL8 were
      equally potent to recruit neutrophils to the peritoneal cavity. CONCLUSIONS: In
      terms of their ability to induce neutrophil recruitment in vivo, the multiple
      CXCL8 forms may be divided in three groups. The first group includes CXCL8
      proteins consisting of 75 to 79 amino acids, cleaved by aminopeptidases, with
      intermediate activity on neutrophils. The second group, generated through
      proteolytic cleavage (e.g. by Ser proteases), contains 69 to 72 amino acid forms
      which are highly potent neutrophil attractants in vivo. A third category is
      generated through the modification of the arginine in the NH(2)-terminal region
      into citrulline by peptidylarginine deiminases and has weak potency to induce
      neutrophil extravasation.

PMID- 21904598
TI  - DELLA-induced early transcriptional changes during etiolated development in
      Arabidopsis thaliana.
AB  - The hormones gibberellins (GAs) control a wide variety of processes in plants,
      including stress and developmental responses. This task largely relies on the
      activity of the DELLA proteins, nuclear-localized transcriptional regulators that
      do not seem to have DNA binding capacity. The identification of early target
      genes of DELLA action is key not only to understand how GAs regulate
      physiological responses, but also to get clues about the molecular mechanisms by
      which DELLAs regulate gene expression. Here, we have investigated the global,
      early transcriptional response triggered by the Arabidopsis DELLA protein GAI
      during skotomorphogenesis, a developmental program tightly regulated by GAs. Our
      results show that the induction of GAI activity has an almost immediate effect on
      gene expression. Although this transcriptional regulation is largely mediated by
      the PIFs and HY5 transcription factors based on target meta-analysis, additional
      evidence points to other transcription factors that would be directly involved in
      DELLA regulation of gene expression. First, we have identified cis elements
      recognized by Dofs and type-B ARRs among the sequences enriched in the promoters
      of GAI targets; and second, an enrichment in additional cis elements appeared
      when this analysis was extended to a dataset of early targets of the DELLA
      protein RGA: CArG boxes, bound by MADS-box proteins, and the E-box CACATG that
      links the activity of DELLAs to circadian transcriptional regulation. Finally,
      Gene Ontology analysis highlights the impact of DELLA regulation upon the
      homeostasis of the GA, auxin, and ethylene pathways, as well as upon pre-existing
      transcriptional networks.

PMID- 21904599
TI  - Association of organophosphate pesticide exposure and paraoxonase with birth
      outcome in Mexican-American women.
AB  - BACKGROUND: Epidemiologic studies suggest that maternal organophosphorus (OP)
      pesticide exposure is associated with poorer fetal growth, but findings are
      inconsistent. We explored whether paraoxonase (PON1), a key enzyme involved in
      detoxification of OPs, could be an effect modifier in this association. METHODS:
      The study population included 470 pregnant women enrolled in the CHAMACOS Study,
      a longitudinal cohort study of mothers and children living in an agricultural
      region of California. We analyzed urine samples collected from mothers twice
      during pregnancy for dialkyl phosphate (DAP) metabolites of OP pesticides. We
      analyzed maternal and fetal (cord) blood samples for PON1 genotype (PON1(192) and
      PON1(-108)) and enzyme activity (paraoxonase and arylesterase). Infant birth
      weight, head circumference, and gestational age were obtained from medical
      records. RESULTS: Infants' PON1 genotype and activity were associated with birth
      outcome, but mothers' were not. Infants with the susceptible PON1(-108TT)
      genotype had shorter gestational age (beta = -0.5 weeks, 95% Confidence Interval
      (CI): -0.9, 0.0) and smaller head circumference (beta = -0.4 cm, 95% CI: -0.7,
      0.0) than those with the PON1(-108CC) genotype. Infants' arylesterase and
      paraoxonase activity were positively associated with gestational age. There was
      some evidence of effect modification with DAPs: maternal DAP concentrations were
      associated with shorter gestational age only among infants of the susceptible
      PON1(-108TT) genotype (p-value(interaction) = 0.09). However, maternal DAP
      concentrations were associated with larger birth weight (p-value(interaction) =
      0.06) and head circumference (p-value(interaction)<0.01) in infants with non
      susceptible genotypes. CONCLUSIONS: Infants whose PON1 genotype and enzyme
      activity levels suggested that they might be more susceptible to the effects of
      OP pesticide exposure had decreased fetal growth and length of gestation. PON1
      may be another factor contributing to preterm or low birth weight birth.

PMID- 21904600
TI  - Age as a criterion for setting priorities in health care? A survey of the German
      public view.
AB  - Although the German health care system has budget constraints similar to many
      other countries worldwide, a discussion on prioritization has not gained the
      attention of the public yet. To probe the acceptance of priority setting in
      medicine, a quantitative survey representative for the German public (n = 2031)
      was conducted. Here we focus on the results for age, a highly disputed criterion
      for prioritizing medical services. This criterion was investigated using
      different types of questionnaire items, from abstract age-related questions to
      health care scenarios, and discrete choice settings, all performed within the
      same sample. Several explanatory variables were included to account for
      differences in preference; in particular, interviewee's own age but also his or
      her sex, socioeconomic status, and health status. There is little evidence that
      the German public accepts age as a criterion to prioritize health care services.

PMID- 21904601
TI  - Intradermal indocyanine green for in vivo fluorescence laser scanning microscopy
      of human skin: a pilot study.
AB  - BACKGROUND: In clinical diagnostics, as well as in routine dermatology, the
      increased need for non-invasive diagnosis is currently satisfied by reflectance
      laser scanning microscopy. However, this technique has some limitations as it
      relies solely on differences in the reflection properties of epidermal and dermal
      structures. To date, the superior method of fluorescence laser scanning
      microscopy is not generally applied in dermatology and predominantly restricted
      to fluorescein as fluorescent tracer, which has a number of limitations.
      Therefore, we searched for an alternative fluorophore matching a novel skin
      imaging device to advance this promising diagnostic approach.
      METHODOLOGY/PRINCIPAL FINDINGS: Using a Vivascope(r)-1500 Multilaser microscope,
      we found that the fluorophore Indocyanine-Green (ICG) is well suited as a
      fluorescent marker for skin imaging in vivo after intradermal injection. ICG is
      one of few fluorescent dyes approved for use in humans. Its fluorescence
      properties are compatible with the application of a near-infrared laser, which
      penetrates deeper into the tissue than the standard 488 nm laser for fluorescein.
      ICG-fluorescence turned out to be much more stable than fluorescein in vivo,
      persisting for more than 48 hours without significant photobleaching whereas
      fluorescein fades within 2 hours. The well-defined intercellular staining pattern
      of ICG allows automated cell-recognition algorithms, which we accomplished with
      the free software CellProfiler, providing the possibility of quantitative high
      content imaging. Furthermore, we demonstrate the superiority of ICG-based
      fluorescence microscopy for selected skin pathologies, including dermal nevi,
      irritant contact dermatitis and necrotic skin. CONCLUSIONS/SIGNIFICANCE: Our
      results introduce a novel in vivo skin imaging technique using ICG, which
      delivers a stable intercellular fluorescence signal ideal for morphological
      assessment down to sub-cellular detail. The application of ICG in combination
      with the near infrared laser opens new ways for minimal-invasive diagnosis and
      monitoring of skin disorders.

PMID- 21904602
TI  - O-GlcNAc modification of NFkappaB p65 inhibits TNF-alpha-induced inflammatory
      mediator expression in rat aortic smooth muscle cells.
AB  - BACKGROUND: We have shown that glucosamine (GlcN) or O-(2-acetamido-2-deoxy-D
      glucopyranosylidene)amino-N-phenylcarbamate (PUGNAc) treatment augments O-linked
      N-acetylglucosamine (O-GlcNAc) protein modification and attenuates inflammatory
      mediator expression, leukocyte infiltration and neointima formation in balloon
      injured rat carotid arteries and have identified the arterial smooth muscle cell
      (SMC) as the target cell in the injury response. NFkappaB signaling has been
      shown to mediate the expression of inflammatory genes and neointima formation in
      injured arteries. Phosphorylation of the p65 subunit of NFkappaB is required for
      the transcriptional activation of NFkappaB. This study tested the hypothesis that
      GlcN or PUGNAc treatment protects vascular SMCs against tumor necrosis factor
      (TNF)-alpha induced inflammatory stress by enhancing O-GlcNAcylation and
      inhibiting TNF-alpha induced phosphorylation of NFkappaB p65, thus inhibiting
      NFkappaB signaling. METHODOLOGY/PRINCIPAL FINDINGS: Quiescent rat aortic SMCs
      were pretreated with GlcN (5 mM), PUGNAc (10(-4) M) or vehicle and then
      stimulated with TNF-alpha (10 ng/ml). Both treatments inhibited TNF-alpha-induced
      expression of chemokines [cytokine-induced neutrophil chemoattractant (CINC)
      2beta and monocyte chemotactic protein (MCP)-1] and adhesion molecules [vascular
      cell adhesion molecule (VCAM)-1 and P-Selectin]. Both treatments inhibited TNF
      alpha induced NFkappaB p65 activation and promoter activity, increased NFkappaB
      p65 O-GlcNAcylation and inhibited NFkappaB p65 phosphorylation at Serine 536,
      thus promoting IkappaBalpha binding to NFkappaB p65. CONCLUSIONS: There is a
      reciprocal relationship between O-GlcNAcylation and phosphorylation of NFkappaB
      p65, such that increased NFkappaB p65 O-GlcNAc modification inhibits TNF-alpha
      Induced expression of inflammatory mediators through inhibition of NFkappaB p65
      signaling. These findings provide a mechanistic basis for our previous
      observations that GlcN and PUGNAc treatments inhibit inflammation and remodeling
      induced by acute endoluminal arterial injury.

PMID- 21904604
TI  - Genomic organization, molecular diversification, and evolution of antimicrobial
      peptide myticin-C genes in the mussel (Mytilus galloprovincialis).
AB  - Myticin-C is a highly variable antimicrobial peptide associated to immune
      response in Mediterranean mussel (Mytilus galloprovincialis). In this study, we
      tried to ascertain the genetic organization and the mechanisms underlying myticin
      C variation and evolution of this gene family. We took advantage of the large
      intron size variation to find out the number of myticin-C genes. Using fragment
      analysis a maximum of four alleles was detected per individual at both introns in
      a large mussel sample suggesting a minimum of two myticin-C genes. The
      transmission pattern of size variants in two full-sib families was also used to
      ascertain the number of myticin-C genes underlying the variability observed.
      Results in both families were in accordance with two myticin-C genes organized in
      tandem. A more detailed analysis of myticin-C variation was carried out by
      sequencing a large sample of complementary (cDNA) and genomic DNA (gDNA) in 10
      individuals. Two basic sequences were detected at most individuals and several
      sequences were constituted by combination of two different basic sequences,
      strongly suggesting somatic recombination or gene conversion. Slight within-basic
      sequence variation detected in all individuals was attributed to somatic
      mutation. Such mutations were more frequently at the C-terminal domain and mostly
      determined non-synonymous substitutions. The mature peptide domain showed the
      highest variation both in the whole cDNA and in the basic-sequence samples, which
      is in accordance with the pathogen recognition function associated to this
      domain. Although most tests suggested neutrality for myticin-C variation,
      evidence indicated positive selection in the mature peptide and C-terminal
      region. Three main highly supported clusters were observed when reconstructing
      phylogeny on basic sequences, meiotic recombination playing a relevant role on
      myticin-C evolution. This study demonstrates that mechanisms to generate
      molecular variation similar to that observed in vertebrates are also operating in
      molluscs.

PMID- 21904603
TI  - Dietary alpha-eleostearic acid ameliorates experimental inflammatory bowel
      disease in mice by activating peroxisome proliferator-activated receptor-gamma.
AB  - BACKGROUND: Treatments for inflammatory bowel disease (IBD) are modestly
      effective and associated with side effects from prolonged use. As there is no
      known cure for IBD, alternative therapeutic options are needed. Peroxisome
      proliferator-activated receptor-gamma (PPARgamma) has been identified as a
      potential target for novel therapeutics against IBD. For this project, compounds
      were screened to identify naturally occurring PPARgamma agonists as a means to
      identify novel anti-inflammatory therapeutics for experimental assessment of
      efficacy. METHODOLOGY/PRINCIPAL FINDINGS: Here we provide complementary
      computational and experimental methods to efficiently screen for PPARgamma
      agonists and demonstrate amelioration of experimental IBD in mice, respectively.
      Computational docking as part of virtual screening (VS) was used to test binding
      between a total of eighty-one compounds and PPARgamma. The test compounds
      included known agonists, known inactive compounds, derivatives and stereoisomers
      of known agonists with unknown activity, and conjugated trienes. The compound
      identified through VS as possessing the most favorable docked pose was used as
      the test compound for experimental work. With our combined methods, we have
      identified alpha-eleostearic acid (ESA) as a natural PPARgamma agonist. Results
      of ligand-binding assays complemented the screening prediction. In addition, ESA
      decreased macrophage infiltration and significantly impeded the progression of
      IBD-related phenotypes through both PPARgamma-dependent and -independent
      mechanisms in mice with experimental IBD. CONCLUSIONS/SIGNIFICANCE: This study
      serves as the first significant step toward a large-scale VS protocol for natural
      PPARgamma agonist screening that includes a massively diverse ligand library and
      structures that represent multiple known target pharmacophores.

PMID- 21904605
TI  - The response of Lactococcus lactis to membrane protein production.
AB  - BACKGROUND: The biogenesis of membrane proteins is more complex than that of
      water-soluble proteins, and recombinant expression of membrane proteins in
      functional form and in amounts high enough for structural and functional studies
      is often problematic. To better engineer cells towards efficient protein
      production, we set out to understand and compare the cellular consequences of the
      overproduction of both classes of proteins in Lactococcus lactis, employing a
      combined proteomics and transcriptomics approach. METHODOLOGY AND FINDINGS:
      Highly overproduced and poorly expressed membrane proteins both resulted in
      severe growth defects, whereas amplified levels of a soluble substrate receptor
      had no effect. In addition, membrane protein overproduction evoked a general
      stress response (upregulation of various chaperones and proteases), which is
      probably due to accumulation of misfolded protein. Notably, upon the expression
      of membrane proteins a cell envelope stress response, controlled by the two
      component regulatory CesSR system, was observed. CONCLUSIONS: The physiological
      response of L. lactis to the overproduction of several membrane proteins was
      determined and compared to that of a soluble protein, thus offering better
      understanding of the bottlenecks related to membrane protein production and
      valuable knowledge for subsequent strain engineering.

PMID- 21904606
TI  - Impact of early growth on postprandial responses in later life.
AB  - BACKGROUND: Low birth weight and slow growth during infancy are associated with
      increased rates of chronic diseases in adulthood. Associations with risk factors
      such as fasting glucose and lipids concentrations are weaker than expected based
      on associations with disease. This could be explained by differences in
      postprandial responses, which, however, have been little studied. Our aim was to
      examine the impact of growth during infancy on postprandial responses to a fast
      food meal (FF-meal) and a meal, which followed the macro-nutrient composition of
      the dietary guidelines (REC-meal). METHODOLOGY/PRINCIPAL FINDINGS: We recruited
      24 overweight 65-75 year-old subjects, 12 with slow growth during infancy (SGI
      group) and 12 with normal early growth. All the subjects were born at term. The
      study meals were isocaloric and both meals were consumed once. Plasma glucose,
      insulin, triglycerides (TG) and free fatty acids (FFA) were measured in fasting
      state and over a 4-h period after both meals. Subjects who grew slowly during
      infancy were also smaller at birth. Fasting glucose, insulin or lipid
      concentrations did not differ significantly between the groups. The TG responses
      were higher for the SGI-group both during the FF-meal (P = 0.047) and the REC
      meal (P = 0.058). The insulin responses were significantly higher for the SGI
      group after the FF-meal (P = 0.036). Glucose and FFA responses did not differ
      significantly between the groups. CONCLUSIONS: Small birth size and slow early
      growth predict postprandial TG and insulin responses. Elevated responses might be
      one explanation why subjects who were small at birth and experiencing slow growth
      in infancy are at an increased risk of developing cardiovascular diseases in
      later life.

PMID- 21904607
TI  - Do facial expressions develop before birth?
AB  - BACKGROUND: Fetal facial development is essential not only for postnatal bonding
      between parents and child, but also theoretically for the study of the origins of
      affect. However, how such movements become coordinated is poorly understood. 4-D
      ultrasound visualisation allows an objective coding of fetal facial movements.
      METHODOLOGY/FINDINGS: Based on research using facial muscle movements to code
      recognisable facial expressions in adults and adapted for infants, we defined two
      distinct fetal facial movements, namely "cry-face-gestalt" and "laughter-
      gestalt," both made up of up to 7 distinct facial movements. In this conceptual
      study, two healthy fetuses were then scanned at different gestational ages in the
      second and third trimester. We observed that the number and complexity of
      simultaneous movements increased with gestational age. Thus, between 24 and 35
      weeks the mean number of co-occurrences of 3 or more facial movements increased
      from 7% to 69%. Recognisable facial expressions were also observed to develop.
      Between 24 and 35 weeks the number of co-occurrences of 3 or more movements
      making up a "cry-face gestalt" facial movement increased from 0% to 42%.
      Similarly the number of co-occurrences of 3 or more facial movements combining to
      a "laughter-face gestalt" increased from 0% to 35%. These changes over age were
      all highly significant. SIGNIFICANCE: This research provides the first evidence
      of developmental progression from individual unrelated facial movements toward
      fetal facial gestalts. We propose that there is considerable potential of this
      method for assessing fetal development: Subsequent discrimination of normal and
      abnormal fetal facial development might identify health problems in utero.

PMID- 21904608
TI  - C-terminal substitution of MDM2 interacting peptides modulates binding affinity
      by distinctive mechanisms.
AB  - The complex between the proteins MDM2 and p53 is a promising drug target for
      cancer therapy. The residues 19-26 of p53 have been biochemically and
      structurally demonstrated to be a most critical region to maintain the
      association of MDM2 and p53. Variation of the amino acid sequence in this range
      obviously alters the binding affinity. Surprisingly, suitable substitutions
      contiguous to this region of the p53 peptides can yield tightly binding peptides.
      The peptide variants may differ by a single residue that vary little in their
      structural conformations and yet are characterized by large differences in their
      binding affinities. In this study a systematic analysis into the role of single C
      terminal mutations of a 12 residue fragment of the p53 transactivation domain
      (TD) and an equivalent phage optimized peptide (12/1) were undertaken to
      elucidate their mechanistic and thermodynamic differences in interacting with the
      N-terminal of MDM2. The experimental results together with atomistically detailed
      dynamics simulations provide insight into the principles that govern peptide
      design protocols with regard to protein-protein interactions and peptidomimetic
      design.

PMID- 21904610
TI  - Fragmentation of contaminant and endogenous DNA in ancient samples determined by
      shotgun sequencing; prospects for human palaeogenomics.
AB  - BACKGROUND: Despite the successful retrieval of genomes from past remains, the
      prospects for human palaeogenomics remain unclear because of the difficulty of
      distinguishing contaminant from endogenous DNA sequences. Previous sequence data
      generated on high-throughput sequencing platforms indicate that fragmentation of
      ancient DNA sequences is a characteristic trait primarily arising due to
      depurination processes that create abasic sites leading to DNA breaks.
      METHODOLOGY/PRINCIPALS FINDINGS: To investigate whether this pattern is present
      in ancient remains from a temperate environment, we have 454-FLX pyrosequenced
      different samples dated between 5,500 and 49,000 years ago: a bone from an
      extinct goat (Myotragus balearicus) that was treated with a depurinating agent
      (bleach), an Iberian lynx bone not subjected to any treatment, a human Neolithic
      sample from Barcelona (Spain), and a Neandertal sample from the El Sidron site
      (Asturias, Spain). The efficiency of retrieval of endogenous sequences is below
      1% in all cases. We have used the non-human samples to identify human sequences
      (0.35 and 1.4%, respectively), that we positively know are contaminants.
      CONCLUSIONS: We observed that bleach treatment appears to create a depurination
      associated fragmentation pattern in resulting contaminant sequences that is
      indistinguishable from previously described endogenous sequences. Furthermore,
      the nucleotide composition pattern observed in 5' and 3' ends of contaminant
      sequences is much more complex than the flat pattern previously described in some
      Neandertal contaminants. Although much research on samples with known contaminant
      histories is needed, our results suggest that endogenous and contaminant
      sequences cannot be distinguished by the fragmentation pattern alone.

PMID- 21904609
TI  - The long life of birds: the rat-pigeon comparison revisited.
AB  - The most studied comparison of aging and maximum lifespan potential (MLSP) among
      endotherms involves the 7-fold longevity difference between rats (MLSP 5y) and
      pigeons (MLSP 35y). A widely accepted theory explaining MLSP differences between
      species is the oxidative stress theory, which purports that reactive oxygen
      species (ROS) produced during mitochondrial respiration damage bio-molecules and
      eventually lead to the breakdown of regulatory systems and consequent death.
      Previous rat-pigeon studies compared only aspects of the oxidative stress theory
      and most concluded that the lower mitochondrial superoxide production of pigeons
      compared to rats was responsible for their much greater longevity. This
      conclusion is based mainly on data from one tissue (the heart) using one
      mitochondrial substrate (succinate). Studies on heart mitochondria using pyruvate
      as a mitochondrial substrate gave contradictory results. We believe the
      conclusion that birds produce less mitochondrial superoxide than mammals is
      unwarranted. We have revisited the rat-pigeon comparison in the most
      comprehensive manner to date. We have measured superoxide production (by heart,
      skeletal muscle and liver mitochondria), five different antioxidants in plasma,
      three tissues and mitochondria, membrane fatty acid composition (in seven tissues
      and three mitochondria), and biomarkers of oxidative damage. The only substantial
      and consistent difference that we have observed between rats and pigeons is their
      membrane fatty acid composition, with rats having membranes that are more
      susceptible to damage. This suggests that, although there was no difference in
      superoxide production, there is likely a much greater production of lipid-based
      ROS in the rat. We conclude that the differences in superoxide production
      reported previously were due to the arbitrary selection of heart muscle to source
      mitochondria and the provision of succinate. Had mitochondria been harvested from
      other tissues or other relevant mitochondrial metabolic substrates been used,
      then very different conclusions regarding differences in oxidative stress would
      have been reached.

PMID- 21904611
TI  - CD40-activated B cell cancer vaccine improves second clinical remission and
      survival in privately owned dogs with non-Hodgkin's lymphoma.
AB  - Cell-based active immunotherapy for cancer is a promising novel strategy, with
      the first dendritic cell (DC) vaccine achieving regulatory approval for clinical
      use last year. Manufacturing remains arduous, especially for DC vaccines, and the
      prospect of using cell-based immunotherapy in the adjuvant setting or in
      combination with chemotherapy remains largely untested. Here, we used a
      comparative oncology approach to test the safety and potential efficacy of tumor
      RNA-loaded, CD40-activated B cells in privately owned dogs presenting with non
      Hodgkin's lymphoma (NHL), a clinical scenario that represents not only a major
      problem in veterinary medicine but also a bona fide spontaneous animal model for
      the human condition. When administered to NHL dogs in remission after induction
      chemotherapy, CD40-B cells electroporated ex vivo with autologous tumor RNA
      safely stimulated immunity in vivo. Although chemotherapy plus CD40-B vaccination
      did not improve time-to-progression or lymphoma-specific survival compared to
      dogs treated with chemotherapy alone, vaccination potentiated the effects of
      salvage therapy and improved the rate of durable second remissions as well as
      subsequent lymphoma-specific survival following salvage therapy. Several of these
      relapsed dogs are now long-term survivors and free of disease for more than a
      year. Overall, these clinical and immunological results suggest that cell-based
      CD40 cancer vaccination is safe and synergizes with chemotherapy to improve
      clinical outcome in canine NHL. More broadly, our findings underscore the unique
      value of clinical investigations in tumor-bearing companion animals.

PMID- 21904612
TI  - Presence of RD149 deletions in M. tuberculosis Central Asian Strain 1 isolates
      affect growth and TNFalpha induction in THP-1 monocytes.
AB  - Central Asian Strain 1 (CAS1) is the prevalent Mycobacterium tuberculosis
      genogroup in South Asia. CAS1 strains carry deletions in RD149 and RD152 regions.
      Significance of these deletions is as yet unknown. We compared CAS1 strains with
      RD149 and concurrent RD149-RD152 deletions with CAS1 strains without deletions
      and with the laboratory reference strain, M. tuberculosis H37Rv for growth and
      for induction of TNFalpha, IL6, CCL2 and IL10 in THP-1 cells. Growth of CAS1
      strains with deletions was slower in broth (RD149; p = 0.024 and RD149-RD152; p =
      0.025) than that of strains without deletions. CAS1 strains with RD149 deletion
      strains further showed reduced intracellular growth (p = 0.013) in THP-1 cells as
      compared with strains without deletions, and also as compared with H37Rv (p =
      0.007) and with CAS1 RD149-RD152 deletion strains (p = 0.029). All CAS1 strains
      induced higher levels of TNFalpha and IL10 secretion in THP-1 cells than H37Rv.
      Additionally, CAS1 strains with RD149 deletions induced more TNFalpha secretion
      than those without deletions (p = 0.013). CAS1 RD149 deletion strains from
      extrapulmonary sources showed more rapid growth and induced lower levels of
      TNFalpha and IL6 secretion in THP-1 cells than isolates from pulmonary sources.
      This data suggests that presence of RD149 reduces growth and increases the
      induction of TNFalpha in host cells by CAS1 strains. Differences observed for
      extrapulmonary strains may indicate an adaptation which increases potential for
      dissemination and tropism outside the lung. Overall, we hypothesise that RD149
      deletions generate genetic diversity within strains and impact interactions of
      CAS1 strains with host cells with important clinical consequences.

PMID- 21904613
TI  - Nucleolar accumulation of RNA binding proteins induced by Actinomycin D is
      functional in Trypanosoma cruzi and Leishmania mexicana but not in T. brucei.
AB  - We have recently shown in T. cruzi that a group of RNA Binding Proteins (RBPs),
      involved in mRNA metabolism, are accumulated into the nucleolus in response to
      Actinomycin D (ActD) treatment. In this work, we have extended our analysis to
      other members of the trypanosomatid lineage. In agreement with our previous
      study, the mechanism seems to be conserved in L. mexicana, since both endogenous
      RBPs and a transgenic RBP were relocalized to the nucleolus in parasites exposed
      to ActD. In contrast, in T. brucei, neither endogenous RBPs (TbRRM1 and TbPABP2)
      nor a transgenic RBP from T. cruzi were accumulated into the nucleolus under such
      treatment. Interestingly, when a transgenic TbRRM1 was expressed in T. cruzi and
      the parasites exposed to ActD, TbRRM1 relocated to the nucleolus, suggesting that
      it contains the necessary sequence elements to be targeted to the nucleolus.
      Together, both experiments demonstrate that the mechanism behind nucleolar
      localization of RBPs, which is present in T. cruzi and L. mexicana, is not
      functional in T. brucei, suggesting that it has been lost or retained
      differentially during the evolution of the trypanosomatid lineage.

PMID- 21904614
TI  - Taxonomic chauvinism revisited: insight from parental care research.
AB  - Parental care (any non-genetic contribution by a parent that appears likely to
      increase the fitness of its offspring) is a widespread trait exhibited by a broad
      range of animal taxa. In addition to influencing the fitness of parent(s) and
      offspring, parental care may be inextricably involved in other evolutionary
      processes, such as sexual selection and the evolution of endothermy. Yet, recent
      work has demonstrated that bias related to taxonomy is prevalent across many
      biological disciplines, and research in parental care may be similarly burdened.
      Thus, I used parental care articles published in six leading journals of
      fundamental behavioral sciences (Animal Behaviour, Behavioral Ecology, Behavioral
      Ecology and Sociobiology, Ethology, Hormones and Behavior, and Physiology &
      Behavior) from 2001-2010 (n = 712) to examine the year-to-year dynamics of two
      types of bias related to taxonomy across animals: (1) taxonomic bias, which
      exists when research output is not proportional to the frequency of organisms in
      nature, and (2) taxonomic citation bias, which is a proxy for the breadth of a
      given article-specifically, the proportion of articles cited that refer solely to
      the studied taxon. I demonstrate that research on birds likely represents a
      disproportionate amount of parental care research and, thus, exhibits taxonomic
      bias. Parental care research on birds and mammals also refers to a relatively
      narrow range of taxonomic groups when discussing its context and, thus, exhibits
      taxonomic citation bias. Further, the levels of taxonomic bias and taxonomic
      citation bias have not declined over the past decade despite cautionary messages
      about similar bias in related disciplines--in fact, taxonomic bias may have
      increased. As in Bonnet et al. (2002), my results should not be interpreted as
      evidence of an 'ornithological Mafia' conspiring to suppress other taxonomic
      groups. Rather, I generate several rational hypotheses to determine why bias
      persists and to guide future work.

PMID- 21904615
TI  - A common path to innate immunity to HIV-1 induced by Toll-like receptor ligands
      in primary human macrophages.
AB  - Toll-like receptors (TLR) represent the best characterized receptor family
      transducing innate immune responses, the first line of defense against microbial
      invaders. This study was designed to investigate whether responses through TLR
      inhibit HIV-1 replication in its primary target cells. Primary human macrophages
      and lymphocytes from several different donors and HIV-1 infection in tissue
      culture were used exclusively in this work. We report that ligands of three
      different TLR: LPS, R848, and double stranded RNA, induce a common antiviral
      response in macrophages as assayed by measurement of HIV-1 p24 protein, gag DNA,
      and entry into cells. HIV-1 infection is arrested after efficient entry but prior
      to reverse transcription. TLR-ligand activated cells secrete antiviral factors
      that induce a similar restriction. HIV-1 infection of lymphocytes is not affected
      by exposure to TLR ligands or to antiviral factors secreted by activated
      macrophages. TBK1, but neither NF-kappaB nor JAK-STAT activity, is required in
      macrophages to mount this antiviral response; the combination of p38 MAPK and JNK
      are partially required for induction of antiviral activity. Based on
      transcriptional induction and inhibition, the TLR-linked antiviral activity is
      different from APOBEC3 A or G, interferon-beta, NAMPT, or p21(Cip1). The cell
      type specificity, site of action, and requirement for signaling intermediates
      suggest that the TLR-linked antiviral activity is novel.

PMID- 21904617
TI  - The epidemiological, clinical, and laboratory features of sporadic Creutzfeldt
      Jakob disease patients in China: surveillance data from 2006 to 2010.
AB  - BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rare, rapidly progressive fatal
      central nervous system disorder, which consists of three main catalogues:
      sporadic, familial, and iatrogenic CJD. METHODOLOGY/PRINCIPAL FINDINGS: In China,
      the surveillance for CJD started in 2006, covering 12 provincial Centers for
      Disease Control and Prevention (CDCs) and 15 hospitals. From 2006 to 2010, 624
      suspected patients were referred to China CJD surveillance. The epidemiological,
      clinical and laboratory features of sporadic CJD (sCJD) were analysed. Both
      groups of probable and possible sCJD showed highest incidences in the population
      of 60 to 69 year-olds. The most common presenting symptoms were progressive
      dementia and mental-related symptoms (neurological symptoms including sleeping
      turbulence, depression, anxiety and stress). Among the four main clinical
      manifestations, myoclonus was more frequently observed in the probable sCJD
      patients. About 2/3 of probable sCJD cases showed positive 14-3-3 in CSF and/or
      periodic sharp wave complexes (PSWC) in electroencephalography (EEG). The
      presence of myoclonus was significantly closely related with the appearance of
      PSWC in EEG. Polymorphisms of codon 129 in PRNP of the notified cases revealed a
      highly predominant M129M genotype in Han Chinese. Among 23 genetic human prion
      diseases, ten were D178N/M129M Fatal familial insomnia (FFI) and five were T188K
      genetic CJD (gCJD), possibly indicating a special distribution of gCJD-related
      mutations in Han Chinese. CONCLUSION: From the period of 2006 to 2010, 261
      patients were diagnosed as sCJD and 23 patients were diagnosed as genetic human
      prion diseases in China. The epidemiological, clinical and laboratory analysis
      data were consistent with the characteristics of sporadic CJD, which provide
      insight into the features of CJD in China.

PMID- 21904616
TI  - Associations of HLA-DP variants with hepatitis B virus infection in southern and
      northern Han Chinese populations: a multicenter case-control study.
AB  - BACKGROUND: Human leukocyte antigen DP (HLA-DP) locus has been reported to be
      associated with hepatitis B virus (HBV) infection in populations of Japan and
      Thailand. We aimed to examine whether the association can be replicated in Han
      Chinese populations. METHODOLOGY/PRINCIPAL FINDINGS: Two HLA-DP variants
      rs2395309 and rs9277535 (the most strongly associated SNPs from each HLA-DP
      locus) were genotyped in three independent Han cohorts consisting of 2 805 cases
      and 1 796 controls. By using logistic regression analysis, these two SNPs in the
      HLA-DPA1 and HLA-DPB1 genes were significantly associated with HBV infection in
      Han Chinese populations (P = 0.021~3.36*10(-8) at rs2395309; P = 8.37*10(
      3)~2.68*10(-10) at rs9277535). In addition, the genotype distributions of both
      sites (rs2395309 and rs9277535) were clearly different between southern and
      northern Chinese population (P = 8.95*10(-5) at rs2395309; P = 1.64*10(-9) at
      rs9277535). By using asymptomatic HBV carrier as control group, our study showed
      that there were no associations of two HLA-DP variants with HBV progression (P =
      0.305~0.822 and 0.163~0.881 in southern Chinese population, respectively; P =
      0.097~0.697 and 0.198~0.615 in northern Chinese population, respectively).
      CONCLUSIONS: Our results confirmed that two SNPs (rs2395309 and rs9277535) in the
      HLA-DP loci were strongly associated with HBV infection in southern and northern
      Han Chinese populations, but not with HBV progression.

PMID- 21904618
TI  - Clinical implication of coronary tortuosity in patients with coronary artery
      disease.
AB  - BACKGROUND: Coronary tortuosity (CT) is a common coronary angiography finding.
      The exact pathogenesis, clinical implication and long-term prognosis of CT are
      not fully understood. The purpose of this study is to investigate the clinical
      characteristics of CT in patients with suspected coronary artery disease (CAD) in
      a Chinese population. METHODS: A total of 1010 consecutive patients underwent
      coronary angiography with complaints of chest pain or related symptoms were
      included in the present study (544 male, mean age: 64+/-11 years). CT was defined
      by the finding of >=3 bends (defined as >=45 degrees  change in vessel direction)
      along main trunk of at least one artery in systole and in diastole. Patients with
      or without CAD were further divided into CT-positive and CT-negative groups, all
      patients were followed up for the incidence of major adverse cardiovascular
      events (MACE) for 2 to 4 years. RESULTS: The prevalence of CT was 39.1% in this
      patient cohort and incidence of CT was significantly higher in female patients
      than that in male patients (OR = 2.603, 95%CI 1.897, 3.607, P<0.001). CT was
      positively correlated with essential hypertension (OR = 1.533, 95%CI 1.131,
      2.076, P = 0.006) and negatively correlated with CAD (OR = 0.755, 95%CI 0.574,
      0.994, P = 0.045). MACE during follow up was similar between CAD patients with or
      without CT. CONCLUSIONS: CT is more often seen in females and positively
      correlated with hypertension and negatively correlated with coronary
      atherosclerosis.

PMID- 21904620
TI  - Functional electrical stimulation of intrinsic laryngeal muscles under varying
      loads in exercising horses.
AB  - Bilateral vocal fold paralysis (BVCP) is a life threatening condition and appears
      to be a good candidate for therapy using functional electrical stimulation (FES).
      Developing a working FES system has been technically difficult due to the
      inaccessible location and small size of the sole arytenoid abductor, the
      posterior cricoarytenoid (PCA) muscle. A naturally-occurring disease in horses
      shares many functional and etiological features with BVCP. In this study, the
      feasibility of FES for equine vocal fold paralysis was explored by testing
      arytenoid abduction evoked by electrical stimulation of the PCA muscle. Rheobase
      and chronaxie were determined for innervated PCA muscle. We then tested the
      hypothesis that direct muscle stimulation can maintain airway patency during
      strenuous exercise in horses with induced transient conduction block of the
      laryngeal motor nerve. Six adult horses were instrumented with a single bipolar
      intra-muscular electrode in the left PCA muscle. Rheobase and chronaxie were
      within the normal range for innervated muscle at 0.55+/-0.38 v and 0.38+/-0.19 ms
      respectively. Intramuscular stimulation of the PCA muscle significantly improved
      arytenoid abduction at all levels of exercise intensity and there was no
      significant difference between the level of abduction achieved with stimulation
      and control values under moderate loads. The equine larynx may provide a useful
      model for the study of bilateral fold paralysis.

PMID- 21904619
TI  - IFN-alpha is constitutively expressed in the human thymus, but not in peripheral
      lymphoid organs.
AB  - Type I interferons have been typically studied for their effects in the context
      of bacterial or viral infections. However in this report, we provide evidence
      that Interferon-alpha (IFN-alpha) expressing cells are present in the thymus in
      the absence of infection. We show that pDC express the highest level of IFN-alpha
      and that MxA, which is exclusively expressed after engagement of the type I IFN
      receptor by IFN-alpha/beta, is expressed in normal fetal and post-natal thymus,
      but not in the periphery. The highest level of MxA is expressed in mature
      thymocytes and pDC located in the medulla and at the cortico-medullary junction.
      The anti-microbial peptide LL-37, which is expressed in the thymus, when
      complexed with eukaryotic nucleic acids, induces the secretion of IFN-alpha by
      thymic pDC. This results in the upregulation of MxA expression in responsive
      thymocytes. We propose that the secretion of IFN-alpha in the thymus may function
      to regulate the rate of T cell development and modulate the requirements for the
      selection of developing T cells.

PMID- 21904621
TI  - Whole genome PCR scanning reveals the syntenic genome structure of toxigenic
      Vibrio cholerae strains in the O1/O139 population.
AB  - Vibrio cholerae is commonly found in estuarine water systems. Toxigenic O1 and
      O139 V. cholerae strains have caused cholera epidemics and pandemics, whereas the
      nontoxigenic strains within these serogroups only occasionally lead to disease.
      To understand the differences in the genome and clonality between the toxigenic
      and nontoxigenic strains of V. cholerae serogroups O1 and O139, we employed a
      whole genome PCR scanning (WGPScanning) method, an rrn operon-mediated fragment
      rearrangement analysis and comparative genomic hybridization (CGH) to analyze the
      genome structure of different strains. WGPScanning in conjunction with CGH
      revealed that the genomic contents of the toxigenic strains were conservative,
      except for a few indels located mainly in mobile elements. Minor nucleotide
      variation in orthologous genes appeared to be the major difference between the
      toxigenic strains. rrn operon-mediated rearrangements were infrequent in El Tor
      toxigenic strains tested using I-CeuI digested pulsed-field gel electrophoresis
      (PFGE) analysis and PCR analysis based on flanking sequence of rrn operons. Using
      these methods, we found that the genomic structures of toxigenic El Tor and O139
      strains were syntenic. The nontoxigenic strains exhibited more extensive sequence
      variations, but toxin coregulated pilus positive (TCP+) strains had a similar
      structure. TCP+ nontoxigenic strains could be subdivided into multiple lineages
      according to the TCP type, suggesting the existence of complex intermediates in
      the evolution of toxigenic strains. The data indicate that toxigenic O1 El Tor
      and O139 strains were derived from a single lineage of intermediates from complex
      clones in the environment. The nontoxigenic strains with non-El Tor type TCP may
      yet evolve into new epidemic clones after attaining toxigenic attributes.

PMID- 21904622
TI  - Utility of survival motor neuron ELISA for spinal muscular atrophy clinical and
      preclinical analyses.
AB  - OBJECTIVES: Genetic defects leading to the reduction of the survival motor neuron
      protein (SMN) are a causal factor for Spinal Muscular Atrophy (SMA). While there
      are a number of therapies under evaluation as potential treatments for SMA, there
      is a critical lack of a biomarker method for assessing efficacy of therapeutic
      interventions, particularly those targeting upregulation of SMN protein levels.
      Towards this end we have engaged in developing an immunoassay capable of
      accurately measuring SMN protein levels in blood, specifically in peripheral
      blood mononuclear cells (PBMCs), as a tool for validating SMN protein as a
      biomarker in SMA. METHODS: A sandwich enzyme-linked immunosorbent assay (ELISA)
      was developed and validated for measuring SMN protein in human PBMCs and other
      cell lysates. Protocols for detection and extraction of SMN from transgenic SMA
      mouse tissues were also developed. RESULTS: The assay sensitivity for human SMN
      is 50 pg/mL. Initial analysis reveals that PBMCs yield enough SMN to analyze from
      blood volumes of less than 1 mL, and SMA Type I patients' PBMCs show ~90%
      reduction of SMN protein compared to normal adults. The ELISA can reliably
      quantify SMN protein in human and mouse PBMCs and muscle, as well as brain, and
      spinal cord from a mouse model of severe SMA. CONCLUSIONS: This SMN ELISA assay
      enables the reliable, quantitative and rapid measurement of SMN in healthy human
      and SMA patient PBMCs, muscle and fibroblasts. SMN was also detected in several
      tissues in a mouse model of SMA, as well as in wildtype mouse tissues. This SMN
      ELISA has general translational applicability to both preclinical and clinical
      research efforts.

PMID- 21904623
TI  - Human migration through bottlenecks from Southeast Asia into East Asia during
      Last Glacial Maximum revealed by Y chromosomes.
AB  - Molecular anthropological studies of the populations in and around East Asia have
      resulted in the discovery that most of the Y-chromosome lineages of East Asians
      came from Southeast Asia. However, very few Southeast Asian populations had been
      investigated, and therefore, little was known about the purported migrations from
      Southeast Asia into East Asia and their roles in shaping the genetic structure of
      East Asian populations. Here, we present the Y-chromosome data from 1,652
      individuals belonging to 47 Mon-Khmer (MK) and Hmong-Mien (HM) speaking
      populations that are distributed primarily across Southeast Asia and extend into
      East Asia. Haplogroup O3a3b-M7, which appears mainly in MK and HM, indicates a
      strong tie between the two groups. The short tandem repeat network of O3a3b-M7
      displayed a hierarchical expansion structure (annual ring shape), with MK
      haplotypes being located at the original point, and the HM and the Tibeto-Burman
      haplotypes distributed further away from core of the network. Moreover, the East
      Asian dominant haplogroup O3a3c1-M117 shows a network structure similar to that
      of O3a3b-M7. These patterns indicate an early unidirectional diffusion from
      Southeast Asia into East Asia, which might have resulted from the genetic drift
      of East Asian ancestors carrying these two haplogroups through many small bottle
      necks formed by the complicated landscape between Southeast Asia and East Asia.
      The ages of O3a3b-M7 and O3a3c1-M117 were estimated to be approximately 19
      thousand years, followed by the emergence of the ancestors of HM lineages out of
      MK and the unidirectional northward migrations into East Asia.

PMID- 21904624
TI  - Lysophosphatidylinositol causes neurite retraction via GPR55, G13 and RhoA in
      PC12 cells.
AB  - GPR55 was recently identified as a putative receptor for certain cannabinoids,
      and lysophosphatidylinositol (LPI). Recently, the role of cannabinoids as GPR55
      agonists has been disputed by a number of reports, in part, because studies
      investigating GPR55 often utilized overexpression systems, such as the GPR55
      overexpressing HEK293 cells, which make it difficult to deduce the physiological
      role of endogenous GPR55. In the present study, we found that PC12 cells, a
      neural model cell line, express endogenous GPR55, and by using these cells, we
      were able to examine the role of endogenous GPR55. Although GPR55 mRNA and
      protein were expressed in PC12 cells, neither CB(1) nor CB(2) mRNA was expressed
      in these cells. GPR55 was predominantly localized on the plasma membrane in
      undifferentiated PC12 cells. However, GPR55 was also localized in the growth
      cones or the ruffled border in differentiated PC12 cells, suggesting a potential
      role for GPR55 in the regulation of neurite elongation. LPI increased
      intracellular Ca(2+) concentration and RhoA activity, and induced ERK1/2
      phosphorylation, whereas endogenous and synthetic cannabinoids did not, thereby
      suggesting that cannabinoids are not GPR55 agonists. LPI also caused neurite
      retraction in a time-dependent manner accompanied by the loss of neurofilament
      light chain and redistribution of actin in PC12 cells differentiated by NGF. This
      LPI-induced neurite retraction was found to be G(q)-independent and G(13)
      dependent. Furthermore, inactivation of RhoA function via C3 toxin and GPR55
      siRNA knockdown prevented LPI-induced neurite retraction. These results suggest
      that LPI, and not cannabinoids, causes neurite retraction in differentiated PC12
      cells via a GPR55, G(13) and RhoA signaling pathway.

PMID- 21904625
TI  - Structural mechanism of S-adenosyl methionine binding to catechol O
      methyltransferase.
AB  - Methyltransferases possess a homologous domain that requires both a divalent
      metal cation and S-adenosyl-L-methionine (SAM) to catalyze its reactions. The
      kinetics of several methyltransferases has been well characterized; however, the
      details regarding their structural mechanisms have remained unclear to date.
      Using catechol O-methyltransferase (COMT) as a model, we perform discrete
      molecular dynamics and computational docking simulations to elucidate the initial
      stages of cofactor binding. We find that COMT binds SAM via an induced-fit
      mechanism, where SAM adopts a different docking pose in the absence of metal and
      substrate in comparison to the holoenzyme. Flexible modeling of the active site
      side-chains is essential for observing the lowest energy state in the apoenzyme;
      rigid docking tools are unable to recapitulate the pose unless the appropriate
      side-chain conformations are given a priori. From our docking results, we
      hypothesize that the metal reorients SAM in a conformation suitable for donating
      its methyl substituent to the recipient ligand. The proposed mechanism enables a
      general understanding of how divalent metal cations contribute to
      methyltransferase function.

PMID- 21904626
TI  - Novel biomarkers distinguishing active tuberculosis from latent infection
      identified by gene expression profile of peripheral blood mononuclear cells.
AB  - BACKGROUND: Humans infected with Mycobacterium tuberculosis (MTB) can delete the
      pathogen or otherwise become latent infection or active disease. However, the
      factors influencing the pathogen clearance and disease progression from latent
      infection are poorly understood. This study attempted to use a genome-wide
      transcriptome approach to identify immune factors associated with MTB infection
      and novel biomarkers that can distinguish active disease from latent infection.
      METHODOLOGY/PRINCIPAL FINDINGS: Using microarray analysis, we comprehensively
      determined the transcriptional difference in purified protein derivative (PPD)
      stimulated peripheral blood mononuclear cells (PBMCs) in 12 individuals divided
      into three groups: TB patients (TB), latent TB infection individuals (LTBI) and
      healthy controls (HC) (n = 4 per group). A transcriptional profiling of 506
      differentially expressed genes could correctly group study individuals into three
      clusters. Moreover, 55- and 229-transcript signatures for tuberculosis infection
      (TB&LTBI) and active disease (TB) were identified, respectively. The validation
      study by quantitative real-time PCR (qPCR) performed in 83 individuals confirmed
      the expression patterns of 81% of the microarray identified genes. Decision tree
      analysis indicated that three genes of CXCL10, ATP10A and TLR6 could
      differentiate TB from LTBI subjects. Additional validation was performed to
      assess the diagnostic ability of the three biomarkers within 36 subjects, which
      yielded a sensitivity of 71% and specificity of 89%. CONCLUSIONS/SIGNIFICANCE:
      The transcription profiles of PBMCs induced by PPD identified distinctive gene
      expression patterns associated with different infectious status and provided new
      insights into human immune responses to MTB. Furthermore, this study indicated
      that a combination of CXCL10, ATP10A and TLR6 could be used as novel biomarkers
      for the discrimination of TB from LTBI.

PMID- 21904627
TI  - Comparative proteomic analysis of Methanothermobacter themautotrophicus DeltaH in
      pure culture and in co-culture with a butyrate-oxidizing bacterium.
AB  - To understand the physiological basis of methanogenic archaea living on
      interspecies H(2) transfer, the protein expression of a hydrogenotrophic
      methanogen, Methanothermobacter thermautotrophicus strain DeltaH, was
      investigated in both pure culture and syntrophic coculture with an anaerobic
      butyrate oxidizer Syntrophothermus lipocalidus strain TGB-C1 as an H(2) supplier.
      Comparative proteomic analysis showed that global protein expression of
      methanogen cells in the model coculture was substantially different from that of
      pure cultured cells. In brief, in syntrophic coculture, although methanogenesis
      driven energy generation appeared to be maintained by shifting the pathway to the
      alternative methyl coenzyme M reductase isozyme I and cofactor F(420)-dependent
      process, the machinery proteins involved in carbon fixation, amino acid
      synthesis, and RNA/DNA metabolisms tended to be down-regulated, indicating
      restrained cell growth rather than vigorous proliferation. In addition, our
      proteome analysis revealed that alpha subunits of proteasome were differentially
      acetylated between the two culture conditions. Since the relevant modification
      has been suspected to regulate proteolytic activity of the proteasome, the global
      protein turnover rate could be controlled under syntrophic growth conditions. To
      our knowledge, the present study is the first report on N-acetylation of
      proteasome subunits in methanogenic archaea. These results clearly indicated that
      physiological adaptation of hydrogenotrophic methanogens to syntrophic growth is
      more complicated than that of hitherto proposed.

PMID- 21904628
TI  - An artemisinin-derived dimer has highly potent anti-cytomegalovirus (CMV) and
      anti-cancer activities.
AB  - We recently reported that two artemisinin-derived dimers (dimer primary alcohol
      606 and dimer sulfone 4-carbamate 832-4) are significantly more potent in
      inhibiting human cytomegalovirus (CMV) replication than artemisinin-derived
      monomers. In our continued evaluation of the activities of artemisinins in CMV
      inhibition, twelve artemisinin-derived dimers and five artemisinin-derived
      monomers were used. Dimers as a group were found to be potent inhibitors of CMV
      replication. Comparison of CMV inhibition and the slope parameter of dimers and
      monomers suggest that dimers are distinct in their anti-CMV activities. A deoxy
      dimer (574), lacking the endoperoxide bridge, did not have any effect on CMV
      replication, suggesting a role for the endoperoxide bridge in CMV inhibition.
      Differences in anti-CMV activity were observed among three structural analogs of
      dimer sulfone 4-carbamate 832-4 indicating that the exact placement and oxidation
      state of the sulfur atom may contribute to its anti-CMV activity. Of all tested
      dimers, artemisinin-derived diphenyl phosphate dimer 838 proved to be the most
      potent inhibitor of CMV replication, with a selectivity index of approximately
      1500, compared to our previously reported dimer sulfone 4-carbamate 832-4 with a
      selectivity index of about 900. Diphenyl phosphate dimer 838 was highly active
      against a Ganciclovir-resistant CMV strain and was also the most active dimer in
      inhibition of cancer cell growth. Thus, diphenyl phosphate dimer 838 may
      represent a lead for development of a highly potent and safe anti-CMV compound.

PMID- 21904629
TI  - Population structure of an invasive parthenogenetic gastropod in coastal lakes
      and estuaries of northern KwaZulu-Natal, South Africa.
AB  - BACKGROUND: Estuaries and coastal lakes receive little attention despite being
      heavily invaded by non-indigenous invasive species (NIS). In these situations,
      studies of population dynamics in invaded habitats can provide valuable insights
      into how NIS interact with new environments. Tarebia granifera is a prosobranch
      gastropod from south-east Asia which has invaded other sub-tropical parts of the
      world. This study addresses whether a small number of key environmental factors
      influences gastropod communities, and specifically how the population density and
      size structure of T. granifera were influenced by environmental change in
      estuaries and coastal lakes in southern Africa. METHODOLOGY/PRINCIPAL FINDINGS:
      T. granifera's density, number of brooded juveniles and size structure were
      measured at the St. Lucia Estuary, Mgobozeleni Estuary, Lake Sibaya and Lake
      Nhlange. Size structure was classified according to shell height (SH). All
      dissected individuals were found to be female and free from trematode infection.
      Salinity, water depth, temperature, and pH were the main factors correlated with
      population density of gastropod communities. T. granifera often reached densities
      well over 1000 ind. m(-2), displacing indigenous gastropods and becoming a
      dominant component of the benthic community. T. granifera successfully invaded
      estuaries despite frequent exposure to high salinity and desiccation, which could
      together eliminate >97% of the population. The persistence of T. granifera was
      ensured due to its high fecundity and the environmental tolerance of large adults
      (20-30 mm SH) which carried an average of 158+/-12.8 SD brooded juveniles. Repeat
      introductions were not essential for the success of this parthenogenetic NIS.
      CONCLUSION/SIGNIFICANCE: There is a need for a broader study on the reproductive
      biology of T. granifera (including the previously overlooked "brood pouch
      ecology"), which affects population dynamics and may be relevant to other
      parthenogenetic NIS, such as Melanoides tuberculata and Potamopyrgus antipodarum.

PMID- 21904630
TI  - Primary vascular tumors of bone: a spectrum of entities?
AB  - Vascular tumors of bone are a heterogeneous group. Numerous terms have been
      introduced as well as different classification systems. None of the
      classification schemes have been accepted due to lack of consistent terminology,
      accepted histologic criteria, and limited correlation with clinical outcome. It
      is acknowledged that vascular tumors of bone originate from endothelial cells,
      resulting in variable expression of endothelial markers. None of these markers
      are useful to discriminate between benign and malignant lesions. Although
      radiologic appearance is not specific, radiologic multifocality should trigger to
      include a vascular neoplasm in the differential diagnosis. This review gives an
      overview of current literature by describing all different histologic subtypes in
      correspondence with clinical, radiologic and genetic data. We propose the
      classification of vascular tumors of bone according to the three-tiered World
      Health Organization classification scheme for soft tissue tumors dividing
      entities into a benign, intermediate and malignant category. Hemangioma is the
      most often and commonly recognized benign lesion. Epithelioid hemangioma has been
      better defined over the past few years. Based on its locally aggressive behavior
      and occurrence of lymph node metastases, classification within the intermediate
      category could be considered. Angiosarcoma is the only accepted term for high
      grade malignant vascular tumor of bone and so far, epithelioid
      hemangioendothelioma is the only accepted low-grade malignant vascular tumor of
      bone. It is still unclear whether other low-grade malignant vascular tumors of
      bone (e.g. hemangioendothelioma) truly exist. Unfortunately, molecular / genetic
      studies of vascular tumors of bone which might support the proposed
      classification are very sparse.

PMID- 21904631
TI  - IL-17 Expression by macrophages is associated with proliferative inflammatory
      atrophy lesions in prostate cancer patients.
AB  - Intraprostatic leukocyte function may vary depending on local inflammatory or
      malignant cell microenvironment. Interleukin (IL)-17 producing cells play key
      roles in chronic inflammation and autoimmunity. Little is known about the
      relevance of IL-17 producing cells at sites of prostate tissue inflammation
      and/or prostate adenocarcinoma. In this study, we analyzed thirty formalin-fixed
      paraffin-embedded whole-mount radical prostatectomy specimens of prostate cancer
      patients. Immunohistochemistry was employed to identify IL-17 producing cells in
      all sites of mononuclear cell accumulation, noting their relationships to areas
      of prostate cancer, proliferative inflammatory atrophy (PIA), or hyperplastic
      benign tissue. Levels of IL-17 producing cells were similar in zones of benign
      prostate tissue and areas of prostate cancer. Pronounced intraluminal and peri
      glandular IL-17 producing cell accumulations were identified in the mononuclear
      cell infiltrates associated with PIA lesions. Glandular and peri-glandular CD68+
      macrophages and neutrophils were the predominant IL-17 producing cells in PIA
      lesions. The accumulation of IL-17 expressing cells in PIA lesions presents
      direct evidence of an inflammatory microenvironment that may support the
      development of prostate cancer.

PMID- 21904632
TI  - Quantitation of brain edema and localisation of aquaporin 4 expression in
      relation to susceptibility to experimental cerebral malaria.
AB  - The pathogenic mechanisms underlying the occurrence of cerebral malaria (CM) are
      still incompletely understood but, clearly, cerebral complications may result
      from concomitant microvessel obstruction and inflammation. The extent to which
      brain edema contributes to pathology has not been investigated. Using the model
      of P. berghei ANKA infection, we compared brain microvessel morphology of CM
      susceptible and CM-resistant mice. By quantitative planimetry, we provide
      evidence that CM is characterized by enlarged perivascular spaces (PVS). We show
      a dramatic aquaporin 4 (AQP4) upregulation, selectively at the level of
      astrocytic foot processes, in both CM and non-CM disease, but significantly more
      pronounced in mice with malarial-induced neurological syndrome. This suggests
      that a threshold of AQP4 expression is needed to lead to neurovascular pathology,
      a view that is supported by significantly higher levels in mice with clinically
      overt CM. Numbers of intravascular leukocytes significantly correlated with both
      PVS enlargement and AQP4 overexpression. Thus, brain edema could be a
      contributing factor in CM pathogenesis and AQP4, specifically in its astrocytic
      location, a key molecule in this mechanism. Since experimental CM is associated
      with substantial brain edema, it models paediatric CM better than the adult
      syndrome and it is tempting to evaluate AQP4 in the former context. If AQP4
      changes are confirmed in human CM, it may represent a novel target for
      therapeutic intervention.

PMID- 21904633
TI  - Plasma microRNAs as novel biomarkers for early detection of lung cancer.
AB  - A diagnosis of lung cancer at its early stages is vital for improving the
      survival rate of patients. MicroRNAs (miRNAs), a family of 19- to 25-nucleotide
      non-coding small RNAs, are frequently dysregulated in lung cancer. The objective
      of this study was to investigate the potential of circulating miRNAs for early
      detection of lung cancer. We searched the published literature for the miRNA
      microarray data of primary lung cancer and selected 15 miRNAs that were most
      frequently up-regulated in lung cancer tissues. Total plasma RNA including miRNAs
      was isolated, polyadenylated and reverse-transcribed into cDNAs. The levels of
      miRNAs were determined by real-time RT-PCR in 74 lung cancer patients and 68 age
      matched cancer-free controls. We found that the levels of miR-155, miR-197, and
      miR-182 in the plasma of lung cancer including stage I patients were
      significantly elevated compared with controls (P<0.001). The combination of these
      3 miRNAs yielded 81.33% sensitivity and 86.76% specificity in discriminating lung
      cancer patients from controls. The levels of miR-155 and miR-197 were higher in
      the plasma from lung cancer patients with metastasis than in those without
      metastasis (P<0.05) and were significantly decreased in responsive patients
      during chemotherapy (P<0.001). These results indicate that miR-155, miR-197, and
      miR-182 can be potential non-invasive biomarkers for early detection of lung
      cancer.

PMID- 21904634
TI  - NVC-422 topical gel for the treatment of impetigo.
AB  - Impetigo is a highly contagious bacterial skin infection affecting children
      worldwide that is caused by the Gram-positive bacteria Staphylococcus aureus,
      Streptococcus pyogenes, or both. Staphylococcus species can quickly develop drug
      resistance rendering mupirocin, fusidic acid, and erythromycin ineffective.
      Preclinical and clinical studies demonstrated that NVC-422 (N, N-dichloro-2, 2
      dimethyltaurine) rapidly kills pathogens without the development of drug
      resistance. 129 patients with clinically diagnosed impetigo were randomized to
      three dose groups (0.1, 0.5, or 1.5% NVC-422 topical gel) in a study conducted at
      2 centers; 125 patients (97%) had microbiologically confirmed infection.
      Treatment was administered three times a day (TID) for 7 days to all randomized
      subjects. Response was measured at the completion of treatment (Day 8) and 1 week
      post treatment (Day 15) by the Skin Infection Rating Scale (SIRS) and by
      microbiological response. A total of 120 subjects (96%) completed all 7 days of
      treatment and were assessed at end of treatment (EOT). Clinical response rate at
      EOT in the PPC population was excellent in each of the dose groups (84.6%, 87.2%,
      and 92.3% in the 0.1%, 0.5% and 1.5% dose groups respectively). The majority of
      the infections were caused by S. aureus, alone (106/125, 85%) of which
      approximately 10% were MRSA. There were no clinical recurrences in any treatment
      groups. Treatment-emergent adverse events were seen in 5.4% of the subjects
      (7/129) and were mild to moderate and resolved. NVC-422 topical gel administered
      TID was well tolerated, with high rates of clinical and microbiological responses
      for treating impetigo.

PMID- 21904635
TI  - Dynamics of early histopathological changes in GVHD after
      busulphan/cyclophosphamide conditioning regimen.
AB  - Hematopoietic stem cell transplantation (HSCT) is a curative treatment for
      otherwise incurable diseases. Conditioning regimen is an important part of HSCT
      and consists of chemotherapy with or without irradiation. Conditioning exerts
      myelosuppressive, immunosuppressive and antitumor effects, but also contributes
      to HSCT-related complications including graft-versus-host disease (GVHD). Since
      almost 50% of the transplanted patients are conditioned with cytostatics without
      irradiation, we developed and characterized a GVHD mouse model following
      conditioning with busulphan and cyclophosphamide. Recipient Balb/c female mice
      were treated with busulphan (20 mg/kg/day for 4 days) and cyclophosphamide (100
      mg/kg/day for two days). After one day of rest, recipient mice were transplanted
      with 2*10(7) bone marrow and 3*10(7) spleen cells from male C57BL/6 (allogeneic
      group) or female Balb/c (syngeneic/control group) mice. The allogeneic, but not
      syngeneic transplanted mice developed GVHD. Histopathology of the major internal
      organs (liver, pancreas, spleen, lungs, heart and kidney) was examined before
      conditioning start, after conditioning's end and 5, 7 and 21 days after
      transplantation using hematoxylin-eosin staining. Decreased spleen cellularity
      and diminished glycogen content in the liver were observed after conditioning
      regimen. Histopathological changes such as vasculitis, inflammation and apoptotic
      cell forms in liver, spleen, pancreas, lungs and heart were observed in
      allogeneic transplanted mice, however, only hypocellular spleen and extramedullar
      hematopoiesis were detected in syngeneic transplanted animals. No morphological
      changes were observed in kidney in either HSCT setting. This is the first study
      describing early histopathological changes after conditioning regimen with
      busulphan/cyclophosphamide and dynamics of GVHD development in several major
      internal organs.

PMID- 21904636
TI  - The selective mineralocorticoid receptor antagonist eplerenone is protective in
      mild anti-GBM glomeru-lonephritis.
AB  - BACKGROUND: Growing evidence suggests that blockade of the aldosterone-receptor
      may preserve kidney function by anti-inflammatory effects independent of the
      blood pressure. We hypothesized that the selective aldosterone-receptor
      antagonist eplerenone has a profound anti-inflammatory effect in the autologous
      phase of anti-glomerular basement membrane (GBM) glomerulonephritis (GN).
      METHODS: Mice received ~200mg/kg body wt/day eplerenone via supplemented chow
      diet or standard chow starting at the day of immunization with rabbit IgG. Three
      days later the anti-GBM antibody was injected and the experiments were stopped at
      day 7 and 14. RESULTS: Mice receiving eplerenone showed significantly decreased
      albuminuria and glomerular sclerosis at day 7 and 14 after induction of anti-GBM
      GN. Eplerenone treatment significantly inhibited the infiltration of CD4+, CD8+ T
      cells and macrophages into the kidneys. Circulating levels and glomerular
      deposition of autologous IgG were comparable in both groups. At day 7 the pro
      inflammatory cytokines MCP-1 and IL-6 were found to be significantly decreased in
      regional draining lymph nodes of eplerenone-treated mice, whereas the anti
      inflammatory cytokine IL-10 was significantly upregulated. In line, splenocytes
      from eplerenone-treated nephritic mice produced significantly increased IL-10.
      CONCLUSION: Aldosterone-receptor blockade by eplerenone effectively attenuated
      proteinuria, kidney damage and the inflammatory response in anti-GBM GN by
      significantly decreasing pro-inflammatory cytokines in the regional draining
      lymph nodes of the kidney. Our results suggest that this selective aldosterone
      receptor antagonist is a possible additional tool in the treatment of GN.

PMID- 21904637
TI  - Brain microvasculature and hypoxia-related proteins in Alzheimer's disease.
AB  - Alzheimer's disease (AD) is a progressive, neurodegenerative disease of
      increasing incidence. The pathologic processes that underlie this disorder are
      incompletely understood, however, hypoperfusion/hypoxia is thought to contribute
      to disease pathogenesis. Hypoxia inducible factor 1-alpha (HIF-1alpha), a key
      regulator of cellular responses to hypoxia, is elevated in the microcirculation
      of AD patients. Cerebral hypoxia is a potent stimulus for vascular activation and
      angiogenesis. Microvessels isolated from the brains of AD patients express a
      large number of angiogenic proteins. Despite considerable data in human tissues
      regarding vascular expression of hypoxia-related angiogenic proteins, there is
      little information regarding these proteins in the brain vasculature of
      transgenic AD mice. The objectives of this study were to determine expression of
      HIF-1alpha, angiogenic proteins, angiopoietin-2 (Ang-2), and matrix
      metalloproteinase 2 (MMP2), and survival/apoptotic proteins (Bcl-xL, caspase 3)
      in the cerebromicrovasculature of AD transgenic mice and to determine the direct
      effect of hypoxia on cerebral endothelial expression of these proteins in vitro.
      Cultured brain endothelial cells were subjected to hypoxia for 4-6 h and analyzed
      by western blot and immunofluorescence. Our results demonstrated that HIF-1alpha
      is induced in cultured brain endothelial cells exposed to hypoxia and that
      expression of Ang-2, MMP2 and caspase 3 was elevated and the anti-apoptotic
      protein Bcl-xL decreased. Brain sections from AD and control mice showed that HIF
      1alpha, Ang-2, MMP2 and caspase 3 are elevated and Bcl-xL decreased in the
      microvasculature of AD mice. These data suggest the cerebromicrovasculature is an
      important target for the effects of hypoxia in the AD brain.

PMID- 21904638
TI  - Papillary cystadenofibroma of epididymis: a case report.
AB  - We present the first reported case of papillary cystadenofibroma of the
      epididymis. The tumor occurred in a 46-year-old man. The mass was 3.7 cm and
      included a hemorrhagic fluid-filled cyst. Microscopically, stromal-filled
      papillae were lined by low cuboidal to columnar epithelium. Epithelial cells were
      reactive for cytokeratin 7, cytokeratins AE1/3, and focally in the apical
      cytoplasm for CD10. Focal CD10 reactivity was also noted in the stroma. The
      lesion was negative for alpha-fetoprotein. These findings ruled out other
      lesions, including metastatic renal cell carcinoma.

PMID- 21904639
TI  - Immunohistochemical profile of normal mesothelium and histiocytic/methothelial
      hyperplasia: a case report.
AB  - Immunohistochemical profiles of normal mesothelium and histiocytic/mesothelial
      hyperplasia (HMH) are unknown. A 19-year-old man was treated by thoracoscopic
      resection of bullae of left lung. Histologically, there were cell proliferative
      foci composed of round cells without significant atypia (histiocyte, mesothelium
      and T-lymphocytes). The cell proliferative foci were patch-like, and no invasive
      features were seen. Because it is composed of histiocytes, mesothelium, and T
      lymphocytes, the diagnosis was HMH. Immunohistochemically, cell components of HMH
      showed the following immunoreactions: calrenitin 3+, D2-40 3+, pancytokeratin
      AE1/3 3+, pancytokeratin CAM5.2 3+, cytokeratin (CK) 34betaE12 1+, CK5/6 1+, CK7
      1+, CK8 3+, CK 14 1+, CK18 2+, CK19 2+, p53 10%, Ki67 20%, CD68 3+, CD45 2+, CD45
      RO 2+, vimentin 3+, Ber-EP4 -, CK20 -, EMA -, desmin -, CEA -, CA19-9 -, TTF-1 -,
      S100 protein -, alphasmooth muscle actin -, CD34 -, CD20 -, chromogranin -,
      synaptophysin -, NSE -, CDX2 -, CD56 -, HER2 -, MUC1 -, MUC2 -, MUC5AC -, and
      MUC6 -. The normal mesothelium showed the following immunoprofile: calrenitin 3+,
      D2-40 3+, pancytokeratin AE1/3 3+, pancytokeratin CAM5.2 3+, CK34betaE12 3+,
      CK5/6 2+, CK7 2+, CK8 3+, CK 14 -, CK18 3+, CK19 2+, vimentin 1+, p53 -, Ki67 1%,
      CD68 -, CD45 -, CD45 RO -, Ber-EP4 -, CK20 -, EMA -, desmin -, CEA -, CA19-9 -,
      TTF-1 -, S100 protein -, alpha-smooth muscle actin -, CD34 -, chromogranin -,
      synaptophysin -, NSE -, CDX2 -, CD56 -, HER2 -, MUC1 -, MUC2 -, MUC5AC -, and
      MUC6 -. These findings indicate that the immunoprolfile of mesothelium in HMH was
      immunohistochemically very similar to that of normal mesothelium except for CD68,
      p53 protein, Ki-67 labeling, CD45 and CD45 RO. These indicate that the HMH was
      reactive phenomenon and HMH is composed of hyperplastic mesothelium, histiocytes
      and T-lymphocytes. The immunoprofile of normal mesothelium provide basic
      knowledge of mesothelial pathology.

PMID- 21904640
TI  - 4-hydroxy-2-nonenal-modified glyceraldehyde-3-phosphate dehydrogenase is degraded
      by cathepsin G in rat neutrophils.
AB  - Degradation of oxidized or oxidatively modified proteins is an essential part of
      the antioxidant defenses of cells. 4-Hydroxy-2-nonenal, a major reactive aldehyde
      formed by lipid peroxidation, causes many types of cellular damage. It has been
      reported that 4-hydroxy-2-nonenal-modified proteins are degraded by the ubiquitin
      proteasome pathway or, in some cases, by the lysosomal pathway. However, our
      previous studies using U937 cells showed that 4-hydroxy-2-nonenal-modified
      glyceraldehyde-3-phosphate dehydrogenase is degraded by cathepsin G. In the
      present study, we isolated the 4-hydroxy-2-nonenal-modified glyceraldehyde-3
      phosphate dehydrogenase-degrading enzyme from rat neutrophils to an active
      protein fraction of 28 kDa. Using the specific antibody, the 28 kDa protein was
      identified as cathepsin G. Moreover, the degradation activity was inhibited by
      cathepsin G inhibitors. These results suggest that cathepsin G plays a crucial
      role in the degradation of 4-hydroxy-2-nonenal-modified glyceraldehyde-3
      phosphate dehydrogenase.

PMID- 21904641
TI  - N-acetylcysteine supplementation controls total antioxidant capacity, creatine
      kinase, lactate, and tumor necrotic factor-alpha against oxidative stress induced
      by graded exercise in sedentary men.
AB  - Aim of this study was to evaluate the effects of short-term (7 days) N
      acetylcysteine (NAC) at 1,200 mg daily supplementation on muscle fatigue, maximal
      oxygen uptake (VO(2max)), total antioxidant capacity (TAC), lactate, creatine
      kinase (CK), and tumor necrotic factor-alpha (TNF-alpha). Twenty-nine sedentary
      men (13 controls; 16 in the supplement group) from a randomized control were
      included. At before and after supplementation, fatigue index (FI) was evaluated
      in the quadriceps muscle, and performed a graded exercise treadmill test to
      induce oxidative stress, and as a measure of VO(2max). Blood samples were taken
      before exercise and 20 minutes after it at before and after supplementation, to
      determine TAC, CK, lactate, and TNF-alpha levels. Results showed that FI and
      VO(2max) increased significantly in the supplement group. After exercise
      decreased the levels of TAC and increased lactate, CK, and TNF-alpha of both
      groups at before supplementation. After supplementation, lactate, CK, and TNF
      alpha levels significantly increased and TAC decreased after exercise in the
      control group. Whereas the TAC and lactate levels did not change significantly,
      but CK and TNF-alpha increased significantly in the supplement group. Therefore,
      this results showed that NAC improved the muscle fatigue, VO(2max), maintained
      TAC, controlled lactate production, but had no influence on CK and TNF-alpha.

PMID- 21904642
TI  - Chopper is prodeath regardless of the effect of p75ICD on sensitivity to
      oxidative stress.
AB  - BACKGROUND: The intracellular domain (ICD) of the neurotrophin receptor, p75NTR,
      exhibits variably pro- and antiapoptotic activity and has been implicated in
      neurodegenerative and neurodestructive disease. The molecular determinants of
      these cellular effects are not completely understood. The "Chopper" domain of
      p75ICD has been shown to be proapoptotic in in vitro systems in which p75ICD is
      proapoptotic. The effects of Chopper in systems in which p75ICD is antiapoptotic
      and, therefore, whether or not Chopper accounts for the variability of the
      cellular effects of p75ICD are not known. We therefore examined the effects of
      deletion of Chopper on the effects of p75ICD on in vitro cell culture systems in
      which p75ICD is pro- or antiapoptotic, respectively. RESULTS: In HN33.11 murine
      neuroblastoma-hippocampal neuron hybrid cells, p75ICD is antiapoptotic. In NIH
      3T3 cells, p75ICD is proapoptotic. In both cell lines deletion of the Chopper
      domain from p75ICD decreases the incidence of apoptosis resulting from oxidative
      stress. Thus, irrespective of the nature of the effects of p75ICD on the cell,
      its Chopper domain is proapoptotic. CONCLUSIONS: Expression of p75ICD can enhance
      or attenuate oxidative induction of apoptosis. Variability of the effects of
      p75ICD is not related to variability of the effects of its Chopper domain.

PMID- 21904643
TI  - S-nitrosation of cellular proteins by NO donors in rat embryonic fibroblast 3Y1
      cells: factors affecting S-nitrosation.
AB  - The mechanism of protein S-nitrosation in cells is not fully understood. Using
      rat 3Y1 cells, we addressed this issue. Among S-nitrosothiols and NO donors
      tested, only S-nitrosocysteine (CysNO) induced S-nitrosation when exposed in
      Hanks' balanced salt solution (HBSS) and not in serum-containing general culture
      medium. In HBSS, NO release from CysNO was almost completely abolished by
      sequestering metal ions with a metal chelator without affecting cellular S
      nitrosation. In contrast, L-leucine, a substrate of L-type amino acid
      transporters (LATs), significantly inhibited S-nitrosation. The absence of S
      nitrosation with CysNO in general culture medium resulted not only from a
      competition with amino acids in the medium for LATs but also from
      transnitrosation of cysteine residues in serum albumin. Collectively, these
      results suggest that in simple buffered saline, CysNO-dependent S-nitrosation
      occurs through a cellular incorporation-dependent mechanism, but if it occurs in
      general culture media, it may be through an NO-dependent mechanism.

PMID- 21904644
TI  - Probucol attenuates oxidative stress, energy starvation, and nitric acid
      production following transient forebrain ischemia in the rat hippocampus.
AB  - Oxidative stress and energy depletion are believed to participate in hippocampal
      neuronal damage after forebrain ischemia. This study has been initiated to
      investigate the potential neuroprotective effects of probucol, a lipid-lowering
      drug with strong antioxidant properties, against transient forebrain ischemia
      induced neuronal damage and biochemical abnormalities in rat hippocampal CA1
      region. Adult male Wistar albino rats were subjected to forebrain ischemia and
      injected with probucol for the next 7 successive days, and compared to controls.
      Forebrain ischemia resulted in a significant decrease in the number of intact
      neurons (77%), glutathione (GSH), and adenosine triphosphate (ATP), and a
      significant increase in thiobarbituric acid reactive substances (TBARS) and total
      nitrate/nitrite, (NO(x)) production in hippocampal tissues. The administration of
      probucol attenuated forebrain ischemia-induced neuronal damage, manifested as a
      complete reversal of the decrease in the number of intact neurons, ATP and GSH
      and the increase in TBARS and NO(x) in hippocampal tissues. This study
      demonstrates that probucol treatment abates forebrain ischemia-induced
      hippocampal neuronal loss, energy depletion, and oxidative stress in hippocampal
      CA1 region. Thus, probucol could be a promising neuroprotective agent in the
      treatment of forebrain ischemia.

PMID- 21904645
TI  - A review of the receptor-binding properties of p-synephrine as related to its
      pharmacological effects.
AB  - Bitter orange (Citrus aurantium) extract and its primary protoalkaloid p
      synephrine are used widely in weight loss/weight management and sports
      performance products. Because of structural similarities, the pharmacological
      effects of p-synephrine are widely assumed to be similar to those of ephedrine, m
      synephrine (phenylephrine), and endogenous amine neurotransmitters as
      norepinephrine and epinephrine. However, small structural changes result in the
      receptor binding characteristics of these amines that are markedly different,
      providing a plausible explanation for the paucity of adverse effects associated
      with the wide-spread consumption of p-synephrine in the form of dietary
      supplements as well as in various Citrus foods and juices. This paper summarizes
      the adrenoreceptor binding characteristics of p-synephrine relative to m
      synephrine, norepinephrine, and other amines as related to the observed
      pharmacological effects.

PMID- 21904646
TI  - Activation of Nrf2-regulated glutathione pathway genes by ischemic
      preconditioning.
AB  - Prophylactic pharmacological activation of astrocytic gene expression driven by
      the transcription factor Nrf2 boosts antioxidant defences and protects against
      neuronal loss in ischemia and other disease models. However, the role of Nrf2 in
      mediating endogenous neuroprotective responses is less clear. We recently showed
      that Nrf2 is activated by mild oxidative stress in both rodent and human
      astrocytes. Moreover, brief exposure to ischemic conditions was found to activate
      Nrf2 both in vivo and in vitro, and this was found to contribute to
      neuroprotective ischemic preconditioning. Here we show that transient ischemic
      conditions in vitro and in vivo cause an increase in the expression of Nrf2
      target genes associated with the glutathione pathway, including those involved in
      glutathione biosynthesis and cystine uptake. Taken together, these studies
      indicate that astrocytic Nrf2 may represent an important mediator of endogenous
      neuroprotective preconditioning pathways.

PMID- 21904647
TI  - Hydroxyl radical and its scavengers in health and disease.
AB  - It is generally believed that diseases caused by oxidative stress should be
      treated with antioxidants. However, clinical trials with such antioxidants as
      ascorbic acid and vitamin E, failed to produce the expected beneficial results.
      On the other hand, important biomolecules can be modified by the introduction of
      oxygen atoms by means of non-oxidative hydroxyl radicals. In addition, hydroxyl
      radicals can reduce disulfide bonds in proteins, specifically fibrinogen,
      resulting in their unfolding and scrambled refolding into abnormal spatial
      configurations. Consequences of this reaction are observed in many diseases such
      as atherosclerosis, cancer and neurological disorders, and can be prevented by
      the action of non-reducing substances. Moreover, many therapeutic substances,
      traditionally classified as antioxidants, accept electrons and thus are effective
      oxidants. It is described in this paper that hydroxyl radicals can be generated
      by ferric ions without any oxidizing agent. In view of the well-known damaging
      effect of poorly chelated iron in the human body, numerous natural products
      containing iron binding agents can be essential in the maintenance of human
      health. However, beneficial effects of the great number of phytochemicals that
      are endowed with hydroxyl radical scavenging and/or iron chelating activities
      should not be considered as a proof for oxidative stress.

PMID- 21904648
TI  - Assessment of anti-cytogenotoxic effects of quercetin in animals treated with
      topotecan.
AB  - The present investigation was directed to study the possible chemoprotective
      activity of orally administered quercetin against topotecan-induced cyto- and
      genotoxicity towards mouse somatic cells in vivo. DNA strand breaks, micronuclei
      formation, and mitotic activity were undertaken in the current study as markers
      of cyto- and genotoxicity. Oxidative stress markers such as intracellular
      reactive oxygen species generation, lipid peroxidation, and reduced and oxidized
      glutathione were assessed in bone marrow as a possible mechanism underlying this
      amelioration. Quercetin was neither cytotoxic nor genotoxic in mice at doses
      tested. Pretreatment of mice with quercetin significantly reduced topotecan
      induced genotoxicity and cytotoxicity in bone marrow cells, and these effects
      were dose dependent. Moreover, prior administration of quercetin ahead of
      topotecan challenge ameliorated oxidative stress markers. In conclusion,
      quercetin has a protective role in the abatement of topotecan-induced cyto- and
      genotoxicity in the bone marrow cells of mice that resides, at least in part, on
      its antioxidant effects. Based on the data presented, strategies can be developed
      to decrease the topotecan-induced bone marrow suppression and secondary
      malignancy in cancer patients and medical personnel exposing to topotecan.

PMID- 21904649
TI  - Von Willebrand factor and oxidative stress parameters in acute coronary
      syndromes.
AB  - Considering the role of von Willebrand factor (vWf) in hemostasis, and the role
      of oxidative stress in the development of endothelial dysfunction and
      atherosclerotic disease, the aim of our study was to investigate the relationship
      between vWf, parameters of oxidative stress and different types of acute coronary
      syndromes (ACS). Levels of vWf activity (vWfAct), vWf antigen (vWfAg), nitric
      oxide (estimated through nitrites-NO(2)-), superoxide anion radical (O(2)-),
      hydrogen peroxide (H2O2), index of lipid peroxidation (estimated through
      thiobarbituric acid reactive substances-TBARS), superoxide dismutase (SOD) and
      catalase (CAT) activity of 115 patients were compared with those of 40 healthy
      controls. ACS patients had significantly higher vWfAct and vWfAg levels, as well
      as TBARS levels, while their levels of NO(2)-, H2O2, SOD and CAT activities were
      lower than controls'. vWfAg showed high specificity and sensitivity as a test to
      reveal healthy or diseased subjects. Multivariant logistic regression marked only
      vWfAg and TBARS as parameters that were under independent effect of ACS type. The
      results of our study support the implementation of vWf in clinical rutine and
      into therapeutic targets, and suggest that ACS patients are in need of
      antioxidant supplementation to improve their impaired antioxidant defence.

PMID- 21904650
TI  - A sphingosine kinase form 2 knockout sensitizes mouse myocardium to
      ischemia/reoxygenation injury and diminishes responsiveness to ischemic
      preconditioning.
AB  - Sphingosine kinase (SphK) exhibits two isoforms, SphK1 and SphK2. Both forms
      catalyze the synthesis of sphingosine 1-phosphate (S1P), a sphingolipid involved
      in ischemic preconditioning (IPC). Since the ratio of SphK1:SphK2 changes
      dramatically with aging, it is important to assess the role of SphK2 in IR injury
      and IPC. Langendorff mouse hearts were subjected to IR (30 min equilibration, 50
      min global ischemia, and 40 min reperfusion). IPC consisted of 2 min of ischemia
      and 2 min of reperfusion for two cycles. At baseline, there were no differences
      in left ventricular developed pressure (LVDP), +/- dP/dtmax, and heart rate
      between SphK2 null (KO) and wild-type (WT) hearts. In KO hearts, SphK2 activity
      was undetectable, and SphK1 activity was unchanged compared to WT. Total SphK
      activity was reduced by 53%. SphK2 KO hearts subjected to IR exhibited
      significantly more cardiac damage (37 +/- 1% infarct size) compared with WT (28
      +/- 1% infarct size); postischemic recovery of LVDP was lower in KO hearts. IPC
      exerted cardioprotection in WT hearts. The protective effect of IPC against IR
      was diminished in KO hearts which had much higher infarction sizes (35 +/- 2%)
      compared to the IPC/IR group in control hearts (12 +/- 1%). Western analysis
      revealed that KO hearts had substantial levels of phosphorylated p38 which could
      predispose the heart to IR injury. Thus, deletion of the SphK2 gene sensitizes
      the myocardium to IR injury and diminishes the protective effect of IPC.

PMID- 21904651
TI  - Royal jelly modulates oxidative stress and apoptosis in liver and kidneys of rats
      treated with cisplatin.
AB  - Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of
      cancer and has adverse side effects such as nephrotoxicity and hepatotoxicity.
      The present study was designed to determine the effects of royal jelly (RJ)
      against oxidative stress caused by CDDP injury of the kidneys and liver, by
      measuring tissue biochemical and antioxidant parameters and investigating
      apoptosis immunohistochemically. Twenty-four Sprague Dawley rats were divided
      into four groups, group C: control group received 0.9% saline; group CDDP:
      injected i.p. with cisplatin (CDDP, 7 mg kg(-1) body weight i.p., single dose);
      group RJ: treated for 15 consecutive days by gavage with RJ (300 mg/kg/day);
      group RJ + CDDP: treated by gavage with RJ 15 days following a single injection
      of CDDP. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione S
      transferase (GST), glutathione peroxidase (GSH-Px), and superoxide dismutase
      (SOD) activities were determined in liver and kidney homogenates, and the liver
      and kidney were also histologically examined. RJ elicited a significant
      protective effect towards liver and kidney by decreasing the level of lipid
      peroxidation (MDA), elevating the level of GSH, and increasing the activities of
      GST, GSH-Px, and SOD. In the immunohistochemical examinations were observed
      significantly enhanced apoptotic cell numbers and degenerative changes by
      cisplatin, but these histological changes were lower in the liver and kidney
      tissues of RJ + CDDP group. Besides, treatment with RJ lead to an increase in
      antiapoptotic activity hepatocytes and tubular epithelium. In conclusion, RJ may
      be used in combination with cisplatin in chemotherapy to improve cisplatin
      induced oxidative stress parameters and apoptotic activity.

PMID- 21904654
TI  - Physical activity among cancer survivors and those with no history of cancer- a
      report from the National Health and Nutrition Examination Survey 2003-2006.
AB  - INTRODUCTION: Cancer survivors are at greater risk for chronic diseases that make
      regular physical activity a challenge. The purpose of this manuscript was to
      compare physical activity levels among five-year cancer survivors and those with
      no history of cancer, and to determine risk factors for physical inactivity.
      METHODS: Participants who completed the physical activity monitoring portion of
      the National Health and Nutrition Examination Survey (NHANES) in 2003-04 and 2005
      06 were included in these analyses. Physical activity collected via accelerometer
      was used to determine who completed recommended amounts of physical activity
      according to Centers for Disease Control (CDC) guidelines. Associations between
      physical activity and cancer status were evaluated with multiple logistic
      regressions. RESULTS: 95.5% of five-year cancer survivors and 87.3% of those with
      no cancer history did not meet the CDC guidelines. After adjusting for sex, age,
      race, education and chronic conditions, cancer survivors were 1.7 (95% CI: 1.0,
      2.9) times more likely than those with no cancer history to fail to meet CDC
      guidelines for physical activity. CONCLUSIONS: Neither the general population nor
      cancer survivors met the CDC guidelines for physical activity. Cancer survivors
      were less likely to meet recommendations and may need tailored interventions
      designed to take into account comorbid conditions to increase their physical
      activity levels.

PMID- 21904653
TI  - Positron emission tomography neuroimaging in Parkinson's disease.
AB  - Positron emission tomography (PET) is a nuclear imaging technique, which allows
      in vivo estimations of important physiological parameters such as, glucose
      metabolism and neuroreceptor binding enabling greater understanding of the
      pathophysiology of Parkinson's disease (PD). The review will evaluate the role of
      PET in assessing both the dopaminergic (DA) and non-DA systems in relation to the
      pathophysiology of PD, differential diagnosis, progression of disease and pre
      clinical disease. Medication side effects, genetic forms of PD, the non-motor
      symptoms of PD and alternative restorative approaches will also be discussed in
      relation to how PET imaging can enhance our understanding of these aspects of the
      disease. PET neuroimaging has to date, provided an excellent tool to assess the
      underlying mechanisms of the disease as well as evaluating the complications and
      management of PD and has the potential to be of great clinical value if the
      current limitations of costing and availability are resolved.

PMID- 21904652
TI  - The emerging importance of alpha-L-fucose in human breast cancer: a review.
AB  - Breast cancer cells incorporate the simple sugar alpha-L-fucose (fucose) into
      glycoproteins and glycolipids which, in turn, are expressed as part of the
      malignant phenotype. We have noted that fucose is not simply a bystander
      molecule, but, in fact, contributes to many of the fundamental oncologic
      properties of breast cancer cells. Here, we summarize the evidence from us and
      others that fucose is necessary for key functions of neoplastic progression
      including hematogenous metastasis, tumor invasion through extracellular matrices
      including basement membranes and up-regulation of the Notch signaling system,
      with implications for epithelial-to-mesenchymal transition and activation of
      breast cancer stem cells. Additionally, certain breast cancer biomarkers are
      fucose-rich while a well-known marker of breast cancer progression, soluble E
      selectin, is a known counter-receptor of fucosylated selectin ligands. We provide
      illustrative examples and supportive evidence drawn from work with human breast
      cancer cell lines in vitro as well as clinical studies with human pathologic
      material. And finally, we discuss evidence that fucose (or its absence) is
      central to the mechanisms of action of several experimental targeted therapies
      which may prove useful in breast cancer treatment. We propose that alpha-L-fucose
      is essential in order to construct first, the malignant and then the metastatic
      phenotype of many human breast cancers. This knowledge may inform the search for
      novel treatment approaches in breast cancer.

PMID- 21904655
TI  - 5'- Adenosine monophosphate induced hypothermia reduces early stage myocardial
      ischemia/reperfusion injury in a mouse model.
AB  - Early intervention using hypothermia treatment has been shown to reduce early
      inflammation, apoptosis and infarct size in animal models of cardiac
      ischemia/reperfusion. We have shown that 5'-adenosine monophosphate (5'-AMP) can
      induce a reversible deep hypothermia in mammals. We hypothesize that 5'-AMP
      induced hypothermia (AIH) may reduce ischemic/reperfusion damage following
      myocardial infarct. C57BL/6J male mice were subjected to myocardial ischemia by
      ligating the left anterior descending coronary artery (LAD) followed by
      reperfusion. Compared to euthermic controls, mice given AIH treatment exhibited
      significant inhibition of neutrophil infiltration and a reduction in matrix
      metallopeptidase 9 (MMP-9) expressions in the infarcted myocardium. A decrease in
      terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive
      nuclei in the left ventricle myocardium were also observed. The overall infarct
      size of the heart was significantly smaller in AIH treated mice. Myocardial
      ischemia in mice given 5'-AMP without hypothermia had similar
      ischemia/reperfusion injuries as the euthermic control. Thus, the AIH cardio
      protective effects were primarily hypothermia based.

PMID- 21904656
TI  - Urothelial carcinomas: a focus on human epidermal receptors signaling.
AB  - Bladder cancer is a common malignancy and a frequent cause of cancer-related
      death worldwide. The benefit from current chemotherapy has reached a relative
      plateau, thus identification of molecular targets for better therapy is a high
      priority. Human epidermal receptors constitute a family of receptor tyrosine
      kinases, which appear to be implicated in cellular transformation and can be over
      expressed in a variety of solid tumors. There is preclinical and clinical data
      suggesting the role of EGFR and HER2 in urothelial carcinoma, thus prompting
      clinical investigation of anti-HER targeted therapies attempting to inhibit HER
      induced tumor-promoting signaling. There is significant and dynamic cross-talk
      between HER and other signaling pathways and the identification of the structure
      and function of such cellular networks in the setting of urothelial cancer is a
      complex and difficult task. The development of prognostic and predictive
      biomarkers is needed in order to improve the personalized management of patients
      with urothelial cancer.

PMID- 21904657
TI  - Network modeling of CDF treated pancreatic cancer cells reveals a novel c-myc-p73
      dependent apoptotic mechanism.
AB  - Systems biology and molecular network modeling are important tools that are
      finding application in anti-cancer drug discovery. These technologies can be
      utilized to map and evaluate the entire set of pathways modulated by drugs in
      cancer cells without loosing key details. Such integrated approaches are
      especially useful in understanding the mechanism of action of agents that do not
      have a defined target. Our novel compound CDF (a synthetic analogue of curcumin),
      is one such multi-targeted agent with proven anti-cancer activity in vitro and in
      vivo. However, its mechanism of action is not fully understood, and thus a
      thorough analysis of key pathways targeted by CDF would be important for
      developing targeted and tailored therapy in the future. Applying Ingenuity
      Pathway Analysis (IPA), we have mapped the pathways altered by CDF treatment of
      BxPC-3 pancreatic cancer (PC) cells. Illumina HT-12 microar-rays were performed
      on RNA extracted from CDF treated cells. IPA analysis of gene expression at early
      time point (24 hrs) revealed deregulation of genes in the c-Myc hub. Western blot
      analysis validated the activation of c-Myc, p73 and its downstream pro-apoptotic
      effector Bax with simultaneous down-regulation of Bcl-2 in two distinct
      pancreatic cancer cell lines (BxPC-3 and Colo-357). In order to further delineate
      the role of c-Myc in inducing apoptosis, siRNA silencing technology was used. As
      expected, c-Myc siRNA knockdown resulted in abrogation of the growth inhibitory
      and apoptotic potential of CDF. In conclusion, our results demonstrate a novel c
      Myc driven apoptotic network activated by CDF in PC cells that is independent of
      wild-type p53, and thus warrants further investigation on the clinical utility of
      CDF.

PMID- 21904658
TI  - A systemic review of PET and biology in lung cancer.
AB  - Positron emission tomography imaging with 2-[fluorine-18]-fluoro-2-deoxy-D
      glucose ((18)F-FDG) has been established as a significant molecular imaging
      technique in the management of lung cancer. However, (18)F-FDG accumulation is
      not specific, therefore several other radiotracers targeting hypoxia, cell
      proliferation and amino acid metabolism have been developed for the imaging of
      human cancers. This review summarizes the current data on the correlation between
      the underlying molecular biology and tumor PET accumulation in lung cancer.

PMID- 21904660
TI  - Synthesis and Evaluation of Noviose Replacements on Novobiocin that Manifest Anti
      proliferative Activity.
AB  - Structural modifications to the coumarin core and benzamide side chain of
      novobiocin have successfully transformed the natural product from a selective DNA
      gyrase inhibitor into a potent inhibitor of the Hsp90 C-terminus. However, no SAR
      studies have been conducted on the noviose appendage, which represents the rate
      limiting synthon in the preparation of analogues. Therefore, a series of sugar
      mimics and non-sugar derivatives were synthesized and evaluated to identify
      simplified compounds that exhibit Hsp90 inhibition. Evaluation against two breast
      cancer cell lines demonstrated that replacement of the stereochemical complex
      noviose with simplified alkyl amines increased anti-proliferative activity,
      resulting in novobiocin analogues that manifest IC(50) values in the mid
      nanomolar range.

PMID- 21904659
TI  - HaloTag: a novel reporter gene for positron emission tomography.
AB  - Among the many molecular imaging techniques, reporter gene imaging has been a
      dynamic area of research. The HaloTag protein is a modified haloalkane
      dehalogenase which was designed to covalently bind to synthetic ligands (i.e. the
      HaloTag ligands [HTL]). Covalent bond formation between the HaloTag protein and
      the chloroal-kane within the HTL occurs rapidly under physiological conditions,
      which is highly specific and essentially irreversible. Over the years, HaloTag
      technology has been investigated for various applications such as in vitro/in
      vivo imaging, protein purification/trafficking, high-throughput assays, among
      others. The goal of this study is to explore the use of the HaloTag protein as a
      novel reporter gene for positron emission tomography (PET) imaging. By attaching
      a HaloTag -reactive chloroalkane to 1, 4, 7-triazacyclononane-N, N', N"-triacetic
      acid (NOTA) through hydrophilic linkers, the resulting NOTA-conjugated HTLs were
      labeled with (64)Cu and tested for PET imaging in living mice bearing 4T1-HaloTag
      ECS tumors, which stably express the HaloTag protein on the cell surface.
      Significantly higher uptake of (64)Cu-NOTA-HTL-S (which contains a short
      hydrophilic linker) in the 4T1-HaloTag-ECS than the non-HaloTag-expressing 4T1
      tumors was observed, which demonstrated the HaloTag specificity of (64)Cu-NOTA
      HTL-S and warranted future investigation of the HaloTag protein as a PET reporter
      gene.

PMID- 21904662
TI  - Oxidative injury is a common consequence of BMPR2 mutations.
AB  - BACKGROUND: Hereditary pulmonary arterial hypertension(PAH) is usually caused by
      mutations in BMPR2. Mutations are found throughout the gene, and common molecular
      consequences of different types of mutation are not known. Knowledge of common
      molecular consequences would provide insight into molecular etiology of disease.
      The objective of this study was to determine common molecular consequences across
      classes of BMPR2 mutation. METHODS #ENTITYSTARTX00026; RESULTS: Increased
      superoxide and peroxide production, and alterations in genes associated with
      oxidative stress were a common consequence of stable transfection of vascular
      smooth muscle cells with three distinct classes of BMPR2 mutation, in the ligand
      binding domain, the kinase domain, and the cytoplasmic tail domain. Measurement
      of oxidized lipids in whole lung from transgenic mice expressing a mutation in
      the BMPR2 cytoplasmic tail showed a 50% increase in isoprostanes and a twofold
      increase in isofurans, suggesting increased ROS of mitochondrial origin.
      Immunohistochemistry on BMPR2 transgenic mouse lung showed that oxidative stress
      was vascular-specific. Electron microscopy showed decreased mitochondrial size
      and variability in pulmonary vessels from BMPR2 mutant mice. Measurement of
      oxidized lipids in urine from humans with BMPR2 mutations demonstrated increased
      ROS, regardless of disease status. Immunohistochemistry on HPAH patient lung
      confirmed oxidative stress specific to the vasculature. CONCLUSIONS: Increased
      oxidative stress, likely of mitochondrial origin, is a common consequence of
      BMPR2 mutation across mutation types in cell culture, mice, and humans.

PMID- 21904663
TI  - Intraoperative hyperglycemia augments ischemia reperfusion injury in renal
      transplantation: a prospective study.
AB  - Background. Diabetes is a risk factor for delayed graft function in kidney
      transplantation, and hyperglycemia increases ischemia reperfusion injury in
      animal models. Methods. To explore the role of perioperative hyperglycemia in
      ischemia reperfusion injury, we conducted a prospective study of 40 patients
      undergoing living donor renal transplantation. Blood glucose levels were
      monitored intraoperatively, and serum samples were obtained at the time
      anesthesia was induced and one hour after allograft reperfusion. The percentage
      change in neutrophil gelatinase-associated lipocalin (NGAL), a protein whose
      expression is increased with renal ischemia, was then used to determine the
      extent of injury. Results. In a multivariate model including recipient, donor,
      and transplant factors, recipient blood glucose >160 mg/dL at the time of
      allograft reperfusion (beta 0.19, P-value < 0.01), warm ischemia time >30 minutes
      (beta 0.11, P-value 0.13), and recipient age (beta 0.05, P-value 0.05) were
      associated with percentage change in NGAL. These same predictors were associated
      with the percentage change in creatinine on postoperative day 2. Conclusions.
      Hyperglycemia is associated with increased ischemic injury in renal
      transplantation. Both creatinine and NGAL, a marker of ischemic injury and renal
      function, fall less rapidly in patients with elevated blood glucose.

PMID- 21904661
TI  - Bioprocess forces and their impact on cell behavior: implications for bone
      regeneration therapy.
AB  - Bioprocess forces such as shear stress experienced during routine cell culture
      are considered to be harmful to cells. However, the impact of physical forces on
      cell behavior is an area of growing interest within the tissue engineering
      community, and it is widely acknowledged that mechanical stimulation including
      shear stress can enhance osteogenic differentiation. This paper considers the
      effects of bioprocess shear stress on cell responses such as survival and
      proliferation in several contexts, including suspension-adapted cells used for
      recombinant protein and monoclonal antibody manufacture, adherent cells for
      therapy in suspension, and adherent cells attached to their growth substrates.
      The enhanced osteogenic differentiation that fluid flow shear stress is widely
      found to induce is discussed, along with the tissue engineering of mineralized
      tissue using perfusion bioreactors. Recent evidence that bioprocess forces
      produced during capillary transfer or pipetting of cell suspensions can enhance
      osteogenic responses is also discussed.

PMID- 21904664
TI  - The Role of FRMD7 in Idiopathic Infantile Nystagmus.
AB  - Idiopathic infantile nystagmus (IIN) is an inherited disorder in which the
      nystagmus arises independently of any other symptoms, leading to the speculation
      that the disorder represents a primary defect in the area of the brain
      responsible for ocular motor control. The inheritance patterns are heterogeneous,
      however the most common form is X-linked. FRMD7 resides at Xq26-27 and
      approximately 50% of X-linked IIN families map to this region. Currently 45
      mutations within FRMD7 have been associated with IIN, confirming the importance
      of FRMD7 in the pathogenesis of the disease. Although mutations in FRMD7 are
      known to cause IIN, very little is known about the function of the protein. FRMD7
      contains a conserved N-terminal FERM domain suggesting that it may provide a link
      between the plasma membrane and actin cytoskeleton. Limited studies together with
      the knowledge of the function of other FERM domain containing proteins, suggest
      that FRMD7 may play a role in membrane extension during neuronal development
      through remodeling of the actin cytoskeleton.

PMID- 21904665
TI  - Influence of a hairpin loop on the thermodynamic stability of a DNA oligomer.
AB  - DSC was used to evaluate the mechanism of the thermally induced unfolding of the
      single-stranded hairpin HP = 5'-CGGAATTCCGTCTCCGGAATTCCG-3' and its core duplex D
      (5'-CGGAATTCCG-3')(2). The DSC melting experiments performed at several salt
      concentrations were successfully described for HP and D in terms of a three-state
      transition model HP<->I (intermediate state) <-> S (unfolded single-stranded
      state) and two state transition model D<->2S, respectively. Comparison of the
      model-based thermodynamic parameters obtained for each HP and D transition shows
      that in unfolding of HP only the HP<->I transition is affected by the TCTC loop.
      This observation suggests that in the intermediate state its TCTC loop part
      exhibits significantly more flexible structure than in the folded state while its
      duplex part remains pretty much unchanged.

PMID- 21904666
TI  - The stability of a model substrate for topoisomerase 1-mediated DNA religation
      depends on the presence of mismatched base pairs.
AB  - Topoisomerase 1 (Top1) enzymes regulate DNA superhelicity by forming covalent
      cleavage complexes that undergo controlled rotation. Substitution of nucleoside
      analogs at the +1 position of the DNA duplex relative to the Top1 cleavage site
      inhibits DNA religation. The reduced efficiency for Top1-mediated religation
      contributes to the anticancer activity of widely used anticancer drugs including
      fluoropyrimidines and gemcitabine. In the present study, we report that
      mismatched base pairs at the +1 position destabilize the duplex DNA components
      for a model Top1 cleavage complex formation even though one duplex component does
      not directly include a mismatched base pair. Molecular dynamics simulations
      reveal G-dU and G-FdU mismatched base pairs, but not a G-T mismatched base pair,
      increase flexibility at the Top1 cleavage site, and affect coupling between the
      regions required for the religation reaction to occur. These results demonstrate
      that substitution of dT analogs into the +1 position of the non-scissile strand
      alters the stability and flexibility of DNA contributing to the reduced
      efficiency for Top1-mediated DNA religation. These effects are inherent in the
      DNA duplex and do not require formation of the Top1:DNA complex. These results
      provide a biophysical rationale for the inhibition of Top1-mediated DNA
      religation by nucleotide analog substitution.

PMID- 21904668
TI  - Production and Partial Characterization of Cellulases from Trichoderma sp. IS-05
      Isolated from Sandy Coastal Plains of Northeast Brazil.
AB  - This study evaluated the production of cellulolytic enzymes by Trichoderma sp. IS
      05 strain, isolated from sand dunes, according to its ability to grow on
      cellulose as carbon source. Wheat bran was tested as the carbon source and
      peptone tested as the nitrogen source. Different concentrations of carbon and
      nitrogen were tested using a factorial design to identify optimal cellulase
      activity production. The results showed that media containing wheat bran 4.0%
      (w/v) and peptone 0.25% (w/v) lead to the highest production, 564.0 U L(-1) of
      cellulase, obtained after 2 days of fermentation. The pH and temperature profile
      showed optimal activity at pH 3.0 and 60 degrees C. As for thermostability, the
      cellulase was most tolerant at 60 degrees C, retaining more than 59.6% of maximal
      activity even after 4 hours of incubation. The combination of acid pH, high
      temperature tolerance, and production of cellulase from agro-industrial residues
      by Trichoderma sp. IS-05 offers possibilities condition for the biomass
      hydrolysis process to produce bioethanol.

PMID- 21904667
TI  - Cell-specific aptamers as emerging therapeutics.
AB  - Aptamers are short nucleic acids that bind to defined targets with high affinity
      and specificity. The first aptamers have been selected about two decades ago by
      an in vitro process named SELEX (systematic evolution of ligands by exponential
      enrichment). Since then, numerous aptamers with specificities for a variety of
      targets from small molecules to proteins or even whole cells have been selected.
      Their applications range from biosensing and diagnostics to therapy and target
      oriented drug delivery. More recently, selections using complex targets such as
      live cells have become feasible. This paper summarizes progress in cell-SELEX
      techniques and highlights recent developments, particularly in the field of
      medically relevant aptamers with a focus on therapeutic and drug-delivery
      applications.

PMID- 21904670
TI  - Cost-Effective Production and Optimization of Alkaline Xylanase by Indigenous
      Bacillus mojavensis AG137 Fermented on Agricultural Waste.
AB  - A xylanase producer Bacillus mojavensis strain, called AG137, isolated from
      cotton farm (Kashan-Iran). The optimal xylanase activity reached at 55 degrees C
      & pH 9.0. Enzyme yield was studied using a medium with different agricultural
      wastes as inducers. Xylanase production of about 249.308 IU/mL was achieved at pH
      8 and 37 degrees C, within 48 h submerged fermentation in enzyme production
      medium supplemented with 2% (w/v) oat bran as an optimum carbon source. A mixture
      of 1% (w/v) yeast extract and 1% (w/v) tryptone as optimum nitrogen sources,
      agitation speed 200 rpm, and inoculum size 2% (v/v) were the optimums for maximum
      production. Accordingly, xylanase yield from 194.68 IU/mL under non-optimized
      fermentation condition enhanced to 302.466 IU/mL in optimized condition. Screened
      xylanase is thermostable, presenting 70% stability at 60 degrees C during 30 min.
      Further enzyme incubation in higher temperature caused a decrease in the residual
      enzyme activity, yet it retained 68%-50% of its activity after 1 hour from 45
      degrees C to 55 degrees C. Besides, it is stable in pH 9 and 10, maintaining over
      70% of its activity for 2 h. The enzyme also could preserve 71% and 63% of its
      initial activity after 3 hours of pre-incubation in the same alkaline condition.
      Produced xylanase therefore was introduced as an alkaline-active and stable one,
      displaying suitable thermostability feature, confirmed by HPLC analysis. Hence,
      all xylanase properties highlight its promising uses in industrial scale.

PMID- 21904671
TI  - Accessibility of Enzymatically Delignified Bambusa bambos for Efficient
      Hydrolysis at Minimum Cellulase Loading: An Optimization Study.
AB  - In the present investigation, Bambusa bambos was used for optimization of
      enzymatic pretreatment and saccharification. Maximum enzymatic delignification
      achieved was 84%, after 8 h of incubation time. Highest reducing sugar yield from
      enzyme-pretreated Bambusa bambos was 818.01 mg/g dry substrate after 8 h of
      incubation time at a low cellulase loading (endoglucanase, beta-glucosidase,
      exoglucanase, and xylanase were 1.63 IU/mL, 1.28 IU/mL, 0.08 IU/mL, and 47.93
      IU/mL, respectively). Enzyme-treated substrate of Bambusa bambos was
      characterized by analytical techniques such as Fourier transformed infrared
      spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy
      (SEM). The FTIR spectrum showed that the absorption peaks of several functional
      groups were decreased after enzymatic pretreatment. XRD analysis indicated that
      cellulose crystallinity of enzyme-treated samples was increased due to the
      removal of amorphous lignin and hemicelluloses. SEM image showed that surface
      structure of Bambusa bambos was distorted after enzymatic pretreatment.

PMID- 21904672
TI  - Health-related quality of life in the gender, race, and clinical experience
      trial.
AB  - Background. We report health-related QoL (HRQoL) from GRACE (Gender, Race, And
      Clinical Experience) study by sex and race over 48 weeks. Methods. 429 treatment
      experienced adults (HIV-1 RNA >= 1000 copies/mL) received darunavir/ritonavir
      600/100 mg twice daily plus an appropriate background regimen. QoL was measured
      by the Functional Assessment of HIV Infection (FAHI) questionnaire. Results. 67%
      women and 77% men, including 67.4% black, 76.0% Hispanic, and 73.8% white
      patients, completed the trial. Baseline total FAHI scores were similar between
      sexes and races. Total FAHI of the entire population improved by Week 4 (P <
      .05); near-maximum changes obtained by Week 12 were maintained through Week 48.
      Women and black patients demonstrated larger improvements in total FAHI versus
      men, and Hispanic and white patients, respectively. Conclusion. HRQoL improved in
      all sex and racial/ethnic groups. Sex-based and race-based differences in
      improvements in FAHI subscales may provide insight into subtle differences of HIV
      1 and treatment on HRQoL in different populations.

PMID- 21904669
TI  - Protein kinases and phosphatases in the control of cell fate.
AB  - Protein phosphorylation controls many aspects of cell fate and is often
      deregulated in pathological conditions. Several recent findings have provided an
      intriguing insight into the spatial regulation of protein phosphorylation across
      different subcellular compartments and how this can be finely orchestrated by
      specific kinases and phosphatases. In this review, the focus will be placed on
      (i) the phosphoinositide 3-kinase (PI3K) pathway, specifically on the kinases Akt
      and mTOR and on the phosphatases PP2a and PTEN, and on (ii) the PKC family of
      serine/threonine kinases. We will look at general aspects of cell physiology
      controlled by these kinases and phosphatases, highlighting the signalling
      pathways that drive cell division, proliferation, and apoptosis.

PMID- 21904673
TI  - The Direct Medical Costs of Late Presentation (<350/mm) of HIV Infection over a
      15-Year Period.
AB  - We describe the immediate- and longer-term direct medical costs of care for
      individuals diagnosed with HIV at CD4 counts <350/mm(3) ("late presenters"). We
      collected and stratified by initial CD4 count all inpatient, outpatient, and drug
      costs for all newly diagnosed patients accessing HIV care within Southern Alberta
      from 1/1/1995 to 1/1/2010. 59% of new patients were late presenters. We found
      significantly higher costs for late presenters, especially inpatient costs,
      during the first year after accessing care. Direct medical costs remained almost
      twice as high for late presenters in subsequent years compared to patients
      presenting with CD4 counts >350/mm(3) despite significantly their improved CD4
      counts. The sustained high cost for late presenters has implications for recent
      recommendations for wider routine HIV testing and the earlier initiation of cART.
      Earlier diagnosis and treatment, while increasing the immediate expenditures
      within a population, may produce both direct and indirect cost savings in the
      longer term.

PMID- 21904674
TI  - Depressive symptom clusters and neuropsychological performance in mild
      Alzheimer's and cognitively normal elderly.
AB  - Objectives. Determine the relationship between depressive symptom clusters and
      neuropsychological test performance in an elderly cohort of cognitively normal
      controls and mild Alzheimer's disease (AD). Design. Cross-sectional analysis.
      Setting. Four health science centers in Texas. Participants. 628 elderly
      individuals (272 diagnosed with mild AD and 356 controls) from ongoing
      longitudinal study of Alzheimer's disease. Measurements. Standard battery of
      neuropsychological tests and the 30-item Geriatric Depression Scale with
      regressions model generated on GDS-30 subscale scores (dysphoria, apathy,
      meaninglessness and cognitive impairment) as predictors and neuropsychological
      tests as outcome variables. Follow-up analyses by gender were conducted. Results.
      For AD, all symptom clusters were related to specific neurocognitive domains;
      among controls apathy and cognitive impairment were significantly related to
      neuropsychological functioning. The relationship between performance and symptom
      clusters was significantly different for males and females in each group.
      Conclusion. Findings suggest the need to examine disease status and gender when
      considering the impact of depressive symptoms on cognition.

PMID- 21904675
TI  - The Induction of IgM and IgG Antibodies against HLA or MICA after Lung
      Transplantation.
AB  - The production of IgG HLA antibodies after lung transplantation (LTx) is
      considered to be a major risk factor for the development of chronic rejection,
      represented by the bronchiolitis obliterans syndrome (BOS). It has recently been
      observed that elevated levels of IgM HLA antibodies also correlates with the
      development of chronic rejection in heart and kidney transplantation. This study
      investigates the relationship between IgM and IgG antibodies against HLA and MICA
      after lung transplantation. Serum was collected from 49 patients once prior to
      transplantation and monthly for up to 1 year after lung transplantation was
      analyzed by Luminex to detect IgM and IgG antibodies against HLA and MICA. The
      presence of either IgM or IgG HLA and/or MICA antibodies prior to or after
      transplantation was not related to survival, gender, primary disease, or the
      development of BOS. Additionally, the production of IgG alloantibodies was not
      preceded by an increase in levels of IgM, and IgM levels were not followed by an
      increase in IgG. Under current immune suppressive regimen, although the presence
      of IgM antibodies does not correlate with BOS after LTx, IgM( high) IgG( low) HLA
      class I antibody titers were observed more in patients with BOS compared to
      patients without BOS.

PMID- 21904676
TI  - Nephrotic syndrome in children: from bench to treatment.
AB  - Idiopathic nephrotic syndrome (INS) is the most frequent form of NS in children.
      INS is defined by the association of the clinical features of NS with renal
      biopsy findings of minimal changes, focal segmental glomerulosclerosis (FSGS), or
      mesangial proliferation (MP) on light microscopy and effacement of foot processes
      on electron microscopy. Actually the podocyte has become the favourite candidate
      for constituting the main part of the glomerular filtration barrier. Most cases
      are steroid sensitive (SSINS). Fifty percents of the latter recur frequently and
      necessitate a prevention of relapses by nonsteroid drugs. On the contrary to
      SSINS, steroid resistant nephrotic syndrome (SRINS) leads often to end-stage
      renal failure. Thirty to forty percents of the latter are associated with
      mutations of genes coding for podocyte proteins. The rest is due to one or
      several different circulating factors. New strategies are in development to
      antagonize the effect of the latter.

PMID- 21904678
TI  - Validation of automated white matter hyperintensity segmentation.
AB  - Introduction. White matter hyperintensities (WMHs) are a common finding on MRI
      scans of older people and are associated with vascular disease. We compared 3
      methods for automatically segmenting WMHs from MRI scans. Method. An operator
      manually segmented WMHs on MRI images from a 3T scanner. The scans were also
      segmented in a fully automated fashion by three different programmes. The voxel
      overlap between manual and automated segmentation was compared. Results. Between
      observer overlap ratio was 63%. Using our previously described in-house software,
      we had overlap of 62.2%. We investigated the use of a modified version of SPM
      segmentation; however, this was not successful, with only 14% overlap.
      Discussion. Using our previously reported software, we demonstrated good
      segmentation of WMHs in a fully automated fashion.

PMID- 21904677
TI  - Molecular and genetic basis of inherited nephrotic syndrome.
AB  - Nephrotic syndrome is an heterogeneous disease characterized by increased
      permeability of the glomerular filtration barrier for macromolecules. Podocytes,
      the visceral epithelial cells of glomerulus, play critical role in
      ultrafiltration of plasma and are involved in a wide number of inherited and
      acquired glomerular diseases. The identification of mutations in nephrin and
      other podocyte genes as causes of genetic forms of nephrotic syndrome has
      revealed new important aspects of the pathogenesis of proteinuric kidney diseases
      and expanded our knowledge of the glomerular biology. Moreover, a novel concept
      of a highly dynamic slit diaphragm proteins is emerging. The most significant
      discoveries in our understanding of the structure and function of the glomerular
      filtration barrier are reviewed in this paper.

PMID- 21904679
TI  - The increased activity of liver lysosomal lipase in nonalcoholic Fatty liver
      disease contributes to the development of hepatic insulin resistance.
AB  - We tested the hypothesis that TAG accumulation in the liver induced by short-term
      high-fat diet (HFD) in rats leads to the dysregulation of endogenous TAG
      degradation by lysosomal lipase (LIPA) via lysosomal pathway and is causally
      linked with the onset of hepatic insulin resistance. We found that LIPA could be
      translocated between qualitatively different depots (light and dense lysosomes).
      In contrast to dense lysosomal fraction, LIPA associated with light lysosomes
      exhibits high activity on both intracellular TAG and exogenous substrate and
      prandial- or diet-dependent regulation. On standard diet, LIPA activity was
      upregulated in fasted and downregulated in fed animals. In the HFD group, we
      demonstrated an increased TAG content, elevated LIPA activity, enhanced
      production of diacylglycerol, and the abolishment of prandial-dependent LIPA
      regulation in light lysosomal fraction. The impairment of insulin signalling and
      increased activation of PKCepsilon was found in liver of HFD-fed animals.
      Lipolysis of intracellular TAG, mediated by LIPA, is increased in steatosis
      probably due to the enhanced formation of phagolysosomes. Consequent
      overproduction of diacylglycerol may represent the causal link between HFD
      induced hepatic TAG accumulation and hepatic insulin resistance via PKCepsilon
      activation.

PMID- 21904680
TI  - Overexpression of PGC-1alpha increases fatty acid oxidative capacity of human
      skeletal muscle cells.
AB  - We investigated the effects of PGC-1alpha (peroxisome proliferator-activated
      receptor gamma coactivator-1alpha) overexpression on the oxidative capacity of
      human skeletal muscle cells ex vivo. PGC-1alpha overexpression increased the
      oxidation rate of palmitic acid and mRNA expression of genes regulating lipid
      metabolism, mitochondrial biogenesis, and function in human myotubes. Basal and
      insulin-stimulated deoxyglucose uptake were decreased, possibly due to
      upregulation of PDK4 mRNA. Expression of fast fiber-type gene marker (MHCIIa) was
      decreased. Compared to skeletal muscle in vivo, PGC-1alpha overexpression
      increased expression of several genes, which were downregulated during the
      process of cell isolation and culturing. In conclusion, PGC-1alpha overexpression
      increased oxidative capacity of cultured myotubes by improving lipid metabolism,
      increasing expression of genes involved in regulation of mitochondrial function
      and biogenesis, and decreasing expression of MHCIIa. These results suggest that
      therapies aimed at increasing PGC-1alpha expression may have utility in treatment
      of obesity and obesity-related diseases.

PMID- 21904681
TI  - Aortoesophageal fistula after endovascular aortic aneurysm repair of a mycotic
      thoracic aneurysm.
AB  - Mycotic aneurysms constitute a small proportion of aortic aneurysms. Endovascular
      repair of mycotic aneurysms has been applied with good short-term and midterm
      results. However, the uncommon aortoenteric fistula formation remains a
      potentially fatal complication when repairing such infective aneurysms. We
      present the case of an 80-year-old woman with thoracic and abdominal aortic
      mycotic aneurysms, which were successfully treated with endografting. However,
      the patient presented 3 months later with upper gastrointestinal bleeding
      secondary to erosion of the thoracic graft into the oesophagus. The patient was
      treated conservatively due to the high risk of surgical repair. There is
      currently little exposure to the management of mycotic aortic aneurysms. If
      suspected, imaging of the entire vasculature will aid initial diagnosis and
      highlight the extent of the disease process, allowing for efficient management.
      Aortic endografting for mycotic thoracic aneurysms is a high-risk procedure yet
      is still an appropriate intervention. Aortoenteric fistulae pose a rare but
      severe complication of aortic endografting in this setting.

PMID- 21904683
TI  - Antibacterial activities of actinomycete isolates collected from soils of
      rajshahi, bangladesh.
AB  - This study was performed to isolate actinomycete colonies having antibacterial
      activity from soil samples collected from different places around Rajshahi,
      Bangladesh. Thirty actinomycete colonies were isolated in pure culture from five
      soil samples using Starch-casein-nitrate-agar medium. The isolates were grouped
      in five color series based on their aerial mycelia color and screened for their
      antibacterial activity against a range of test bacteria. Sixteen isolates (53.3%)
      were found to have moderate to high activity against four gram-positive and four
      gram-negative bacteria. Since many isolates showed inhibitory activity against
      indicator bacteria, it is suggestive that Bangladeshi soil could be an
      interesting source to explore for antibacterial secondary metabolites.

PMID- 21904682
TI  - Lipoplatin formulation review article.
AB  - Patented platform technologies have been used for the liposomal encapsulation of
      cisplatin (Lipoplatin) into tumor-targeted 110 nm (in diameter) nanoparticles.
      The molecular mechanisms, preclinical and clinical data concerning lipoplatin,
      are reviewed here. Lipoplatin has been successfully administered in three
      randomized Phase II and III clinical trials. The clinical data mainly include non
      small-cell lung cancer but also pancreatic, breast, and head and neck cancers. It
      is anticipated that lipoplatin will replace cisplatin as well as increase its
      potential applications. For the first time, a platinum drug has shown superiority
      to cisplatin, at least in non-squamous non-small-cell lung cancer as reported in
      a Phase III study which documented a simultaneous lowering of all of the side
      effects of cisplatin.

PMID- 21904684
TI  - Interpretation of controversial teratogenic findings of drugs such as
      phenobarbital.
AB  - Objective. To check the debated association between phenobarbital treatment
      during pregnancy and risk for congenital abnormalities (CAs) in their children.
      Study Design. It is a comparison of phenobarbital treatment in the mothers of
      cases with CA and matched controls without CAs in the Hungarian Case-Control
      Surveillance System of Congenital Abnormalities. Results. Of 22,843 cases with
      CA, 149 (0.65%) had mothers with phenobarbital treatment, while of 38,151 control
      newborn infants without CA, 209 (0.55%) were born to mothers with phenobarbital
      treatment (100-400 mg daily) (OR with 95% CI : 1.3, 1.1-1.7). Of 16 CA groups,
      only hypospadias had a higher risk after phenobarbital treatment in the critical
      period of this CA (OR with 95% CI : 2.4, 1.1-5.4). However, if only medically
      recorded phenobarbital treatments were evaluated and multiple testing bias was
      considered, this association would disappear. Conclusions. This study stresses
      the importance of the exclusion of recall bias and multiple testing bias.

PMID- 21904686
TI  - Cancer and cardiovascular disease.

PMID- 21904685
TI  - GABA neuron alterations, cortical circuit dysfunction and cognitive deficits in
      schizophrenia.
AB  - Schizophrenia is a brain disorder associated with cognitive deficits that
      severely affect the patients' capacity for daily functioning. Whereas our
      understanding of its pathophysiology is limited, postmortem studies suggest that
      schizophrenia is associated with deficits of GABA-mediated synaptic transmission.
      A major role of GABA-mediated transmission may be producing synchronized network
      oscillations which are currently hypothesized to be essential for normal
      cognitive function. Therefore, cognitive deficits in schizophrenia may result
      from a GABA synapse dysfunction that disturbs neural synchrony. Here, we
      highlight recent studies further suggesting alterations of GABA transmission and
      network oscillations in schizophrenia. We also review current models for the
      mechanisms of GABA-mediated synchronization of neural activity, focusing on
      parvalbumin-positive GABA neurons, which are altered in schizophrenia and whose
      function has been strongly linked to the production of neural synchrony.
      Alterations of GABA signaling that impair gamma oscillations and, as a result,
      cognitive function suggest paths for novel therapeutic interventions.

PMID- 21904687
TI  - Gene duplication and the genome distribution of sex-biased genes.
AB  - In species that have two sexes, a single genome encodes two morphs, as each sex
      can be thought of as a distinct morph. This means that the same set of genes are
      differentially expressed in the different sexes. Many questions emanate from this
      statement. What proportion of genes contributes to sexual dimorphism? How do they
      contribute to sexual dimorphism? How is sex-biased expression achieved? Which sex
      and what tissues contribute the most to sex-biased expression? Do sex-biased
      genes have the same evolutionary patterns as nonbiased genes? We review the
      current data on sex-biased expression in species with heteromorphic sex
      chromosomes and comment on the most important hypotheses suggested to explain the
      origin, evolution, and distribution patterns of sex-biased genes. In this
      perspective we emphasize how gene duplication serves as an important molecular
      mechanism to resolve genomic clashes and genetic conflicts by generating sex
      biased genes, often sex-specific genes, and contributes greatly to the underlying
      genetic basis of sexual dimorphism.

PMID- 21904689
TI  - Thyroid carcinoma in children and adolescents-systematic review of the
      literature.
AB  - Thyroid cancer in children and adolescents is usually a major concern for
      physicians, patients, and parents. Controversies regarding the aggressiveness of
      the clinical presentation and the ideal therapeutic approach remain among the
      scientific community. The current recommendations and staging systems are based
      on data generated by studies in adults, and this might lead to overtreating in
      some cases as well as undertreating in others. Understanding the differences in
      the biology, clinical course, and outcomes in this population is crucial for
      therapeutic decisions. This paper evaluates the biology, clinical presentation,
      recurrences, and overall survival as well as the staging systems in children and
      adolescents with differentiated thyroid cancer.

PMID- 21904690
TI  - Effects of the demethylating agent, 5-azacytidine, on expression of the
      kallikrein-kinin genes in carcinoma cells of the lung and pleura.
AB  - Tissue kallikrein (KLK1) and plasma kallikrein (KLKB1) may regulate the growth
      and proliferation of tumours of the lung and pleura, through the generation of
      kinin peptides that signal through the kinin B(1) (BDKRB1) and B(2) (BDKRB2)
      receptors. The development and progression of cancer results from genetic
      mutations, as well as epigenetic changes that include methylation of DNA at CpG
      islands. The aim of this study was to assess whether expression of the kallikrein
      kinin genes in lung cancer and mesothelioma cells is regulated by DNA
      methylation. Quantitative reverse transcriptase-PCR and immunocytochemistry
      showed differences in the basal expression of the kallikrein-kinin genes and
      proteins in lung carcinoma and mesothelioma cells, compared with non-malignant
      lung epithelial and mesothelial cells, respectively. Following treatment with the
      demethylating agent, 5-azacytidine (5-AZA), KLKB1 mRNA expression was
      consistently increased in both lung carcinoma and mesothelioma cells, whereas
      KLK1, BDKRB1 and BDKRB2 mRNA expression was decreased or unchanged. Increased
      expression of KLKB1 after 5-AZA treatment suggests it may function as a tumour
      suppressor gene in cancers of the lung and pleura. Studies on DNA methylation of
      the kallikrein-kinin genes will enhance understanding of their role in
      carcinogenesis and provide insights into the importance of kallikreins as tumour
      biomarkers.

PMID- 21904691
TI  - Prostatic adenocarcinoma metastatic to pleomorphic liposarcoma, a "collision
      phenomenon": report of a case with review of pelvic collision tumors.
AB  - "Collision tumor" is an uncommon phenomenon characterized by coexistence of two
      completely distinct and independent tumors at the same site. Collision tumors
      have been reported in different sites in the body; however, these are
      particularly uncommon in the pelvic cavity. A 70-year-old man, with prior history
      of urothelial and prostate cancer, presented with a large pelvic mass detected on
      imaging studies. Pathological examination revealed a large liposarcoma with
      prostatic carcinoma embedded in it. Immunohistochemistry and florescence in situ
      hybridization studies were performed to reach to a conclusive diagnosis. To the
      best of our knowledge, this is the second case reported till date. We present the
      challenges encountered in the diagnosis of this case and review of pelvic
      collision tumors.

PMID- 21904692
TI  - Oxidative stress in veterinary medicine.

PMID- 21904688
TI  - Similarities in acquired factors related to postmenopausal osteoporosis and
      sarcopenia.
AB  - Postmenopausal population is at increased risk of musculoskeletal impairments.
      Sarcopenia and osteoporosis are associated with significant morbidity and social
      and health-care costs. These two conditions are uniquely linked with similarities
      in pathophysiology and diagnostic methods. Uniform diagnostic criteria for
      sarcopenia are still evolving. Postmenopausal sarcopenia and osteoporosis share
      many environmental risk- and preventive factors. Moreover, geriatric frailty
      syndrome may result from interaction of osteoporosis and sarcopenia and may lead
      to increased mortality. The present paper reviews the factors in evolution of
      postmenopausal sarcopenia and osteoporosis.

PMID- 21904693
TI  - Effect of Feed Restriction during Pregnancy on Performance and Productivity of
      New Zealand White Rabbit Does.
AB  - This study aimed to evaluate effect of stage of feed restriction on performance
      and productivity of pregnant does. New Zealand white female rabbits were randomly
      divided into three groups. Control group was provided daily with 185 g of food
      increased to 200 g from the 15th day of gestation. R(1) was offered daily a
      restricted amount of food (60% restriction, 111 g) for the first half of
      pregnancy and then offered 200 g of food daily till parturition. R(2) was
      provided with 185 g of food daily through the first half of pregnancy and then
      offered daily a restricted amount of food (60% restriction, 120 g) for the second
      half. After parturition, food was provided adlibitum. Maternal body weights,
      litter size, litter weight, and average body weight of kits at kindling of R(1)
      showed no change, whereas R(2) showed significant reduction in the weights of
      does at the 4th week of pregnancy and at kindling. The birth weight and weaning
      weight of R(2) were significantly reduced. The highest mortality was recorded in
      kits of R(2). No significant differences in blood parameters or serum prolactin
      were observed. The serum protein was significantly reduced R(2).

PMID- 21904694
TI  - Differences in change scores and the predictive validity of three commonly used
      measures following concussion in the middle school and high school aged
      population.
AB  - BACKGROUND: A battery of tests is commonly used to measure disability with and
      recovery from concussion. A number of different concussion-oriented assessment
      tests exist and each is considered useful. To the authors' knowledge, no study
      has compared the scores of these tests during recovery in the middle school and
      high school aged population to see how each change over time. PURPOSE: The
      purposes of this study were to analyze clinical data of concussed middle school
      and high school aged athletes to determine the concurrent and predictive validity
      for post-concussion syndrome (PCS) of the Post-Concussion Symptom Scale (PCSS),
      Balance Error Scoring System (BESS), and the five subscales of the Immediate Post
      Concussion Assessment and Cognitive Testing (ImPACT). METHODS: The study was a
      retrospective chart review performed on middle school and high school aged
      individuals with a diagnosis of concussion from the years 2008-2010 within the
      Akron Children's Hospital Sports Medicine system. To be eligible for inclusion in
      the dataset, each subject required a baseline measurement for each of the three
      tests (and all five subscales of the ImPACT) and a post-test measure. The mean
      age of the population was 15.38 years (SD = 1.7) and ranged from 11 to 19 years.
      Pearson product correlation tests (correlation matrix) were used to analyze the
      concurrent validity of the test items during recovery following a concussion.
      Receiver operating characteristics (ROC) curves were used to determine the
      predictive validity of initial scores for developing PCS. RESULTS: The
      correlation matrix captured five statistically significant findings; however,
      these suggested only weak to mild correlations. Five test items yielded an area
      under the curve (AUC) greater than 0.50 but only one was statistically
      significant. After qualitative evaluation, only one of the three tests (including
      the five subscales of the ImPACT) was useful in predicting post-concussion
      syndrome. CONCLUSION: This study suggests that there is poor concurrent validity
      among three commonly used concussion tests and there is no baseline score that
      predicts whether post-concussion syndrome will occur. LEVEL OF EVIDENCE: 2b.

PMID- 21904695
TI  - Management of acute sports injuries and medical conditions by physical
      therapists: assessment via case scenarios.
AB  - PURPOSE/BACKGROUND: Some physical therapists (PTs) provide services at sporting
      events, but there are limited studies investigating whether PTs are properly
      prepared to provide such services. The purpose of this study was to assess acute
      sports injury and medical condition management decision-making skills of PTs.
      METHODS: A Web-based survey presented 17 case scenarios related to acute medical
      conditions and sport injuries. PTs from the Sports Physical Therapy Section of
      The American Physical Therapy Association were e-mailed a cover letter/Web link
      to the survey and invited to participate over a 30-day period. Data were analyzed
      using SPSS 18.0. RESULTS: A total of 411 of 5158 PTs who were members of the
      Sports Physical Therapy Association in 2009 and had valid e-mail addresses
      completed the survey, of which 389 (7.5%) were appropriate for analysis. Over
      75.0% of respondents felt "prepared" or "somewhat prepared" to provide immediate
      care for 13 out of 16 medical conditions, with seizures, spinal cord injuries,
      and internal organ injuries having the lowest percentages. Over 75.0% of the
      respondents made "appropriate" or "overly cautious" decisions for 11 of the 17
      acute injury or medical condition cases. CONCLUSIONS: Results of the current
      study indicate that PTs felt more "prepared" and tended to make "appropriate"
      return to play decisions on the acute sports injury and medical condition case
      studies more often than coaches who participated in a similar study, regardless
      of level of importance of the game or whether the athlete was a starter vs. non
      starter. However, for PTs who plan on assisting at sporting events, additional
      preparation/education may be recommended, such as what is taught in an emergency
      responder course.

PMID- 21904696
TI  - A pilot survey on injury and safety concerns in international sledge hockey.
AB  - OBJECTIVE: To describe sledge hockey injury patterns, safety issues and to
      develop potential injury prevention strategies. DESIGN: Pilot survey study of
      international sledge hockey professionals, including trainers, physiotherapists,
      physicians, coaches and/or general managers. SETTING: Personal encounter or
      online correspondence. RESPONDENTS: Sledge hockey professionals; a total of 10
      respondents from the 5 top-ranked international teams recruited by personal
      encounter or online correspondence. MAIN OUTCOME MEASUREMENTS: Descriptive Data
      reports on sledge athlete injury characteristics, quality of rules and
      enforcement, player equipment, challenges in the medical management during
      competition, and overall safety. RESULTS: Muscle strains and concussions were
      identified as common, and injuries were reported to affect the upper body more
      frequently than the lower body. Overuse and body checking were predominant injury
      mechanisms. Safety concerns included excessive elbowing, inexperienced refereeing
      and inadequate equipment standards. CONCLUSIONS: This paper is the first
      publication primarily focused on sledge hockey injury and safety. This
      information provides unique opportunity for the consideration of implementation
      and evaluation of safety strategies. Safety interventions could include improved
      hand protection, cut-resistant materials in high-risk areas, increased vigilance
      to reduce intentional head-contact, lowered rink boards and modified bathroom
      floor surfacing.

PMID- 21904697
TI  - The influence of heel height on sagittal plane knee kinematics during landing
      tasks in recreationally active and athletic collegiate females.
AB  - PURPOSE: To determine if heel height alters sagittal plane knee kinematics when
      landing from a forward hop or drop landing. BACKGROUND: Knee angles close to
      extension during landing are theorized to increase ACL injury risk in female
      athletes. METHODS: Fifty collegiate females performed two single-limb landing
      tasks while wearing heel lifts of three different sizes (0, 12 & 24 mm) attached
      to the bottom of a sneaker. Using an electrogoniometer, sagittal plane kinematics
      (initial contact [KA(IC)], peak flexion [KA(Peak)], and rate of excursion [RE])
      were examined. Repeated measures ANOVAs were used to determine the influence of
      heel height on the dependent measures. RESULTS: Forward hop task- KA(IC) with 0
      mm, 12 mm, and 24 mm lifts were 8.88+/-6.5, 9.38+/-5.8 and 11.28+/-7.0,
      respectively. Significant differences were noted between 0 and 24 mm lift
      (p<.001) and 12 and 24 mm lifts (p=.003), but not between the 0 and 12 mm
      conditions (p=.423). KA(Peak) with 0 mm, 12 mm, and 24 mm lifts were 47.08+/
      10.9, 48.18+/-10.3 and 48.88+/-9.7, respectively. A significant difference was
      noted between 0 and 24 mm lift (p=.004), but not between the 0 and 12 mm or 12
      and 24 mm conditions (p=.071 and p=.282, respectively). The RE decreased
      significantly from 2128/sec+/-52 with the 12 mm lift to 1958/sec+/-55 with the 24
      mm lift (p=.004). RE did not differ from 0 to 12 or 0 to 24 mm lift conditions
      (p=.351 and p=.086, respectively). Jump-landing task- No significant differences
      were found in KA(IC) (p=.531), KA(Peak) (p=.741), or the RE (p=.190) between any
      of the heel lift conditions. CONCLUSIONS: The addition of a 24 mm heel lift to
      the bottom of a sneaker significantly alters sagittal plane knee kinematics upon
      landing from a unilateral forward hop but not from a drop jump.

PMID- 21904698
TI  - The navicular position test - a reliable measure of the navicular bone position
      during rest and loading.
AB  - BACKGROUND: Lower limb injuries are a large problem in athletes. However, there
      is a paucity of knowledge on the relationship between alignment of the medial
      longitudinal arch (MLA) of the foot and development of such injuries. A reliable
      and valid test to quantify foot type is needed to be able to investigate the
      relationship between arch type and injury likelihood. Feiss Line is a valid
      clinical measure of the MLA. However, no study has investigated the reliability
      of the test. OBJECTIVES: The purpose was to describe a modified version of the
      Feiss Line test and to determine the intra- and inter-tester reliability of this
      new foot alignment test. To emphasize the purpose of the modified test, the
      authors have named it The Navicular Position Test. METHODS: Intra- and inter
      tester reliability were evaluated of The Navicular Position Test with the use of
      ICC (interclass correlation coefficient) and Bland-Altman limits of agreement on
      43 healthy, young, subjects. RESULTS: Inter-tester mean difference -0.35 degrees
      [-1.32; 0.62] p = 0.47. Bland-Altman limits of agreement -6.55 to 5.85 degrees,
      ICC = 0.94. Intra-tester mean difference 0.47 degrees [-0.57; 1.50] p = 0.37.
      Bland-Altman limits of agreement -6.15 to 7.08 degrees, ICC = 0.91. DISCUSSION:
      The present data support The Navicular Position Test as a reliable test of the
      navicular bone position during rest and loading measured in a simple test set-up.
      CONCLUSION: The Navicular Position Test was shown to have a high intraday-, intra
      and inter-tester reliability. When cut off values to categorize the MLA into
      planus, rectus, or cavus feet, has been determined and presented, the test could
      be used in prospective observational studies investigating the role of the arch
      type on the development of various lower limb injuries.

PMID- 21904699
TI  - Shoulder pain and dysfunction secondary to neural injury.
AB  - STUDY DESIGN: Resident's Case Study BACKGROUND/INTRODUCTION: The reports of
      spinal accessory nerve injury in the literature primarily focus on injury
      following surgical dissection or traumatic stretch injury. There is limited
      literature describing the presentation and diagnosis of this injury with an
      unknown cause. The purpose of this case report is to describe the clinical
      decision-making process that guided the diagnosis and treatment of a complex
      patient with spinal accessory nerve palsy (SANP) whose clinical presentation and
      response to therapy were inconsistent with the results of multiple diagnostic
      tests. CASE DESCRIPTION: The patient was a 27-year-old female triathlete with a
      five month history of right-sided neck, anterior shoulder, and chest pain.
      OUTCOME: Based on the physical exam, magnetic resonance imaging, radiographs,
      electrodiagnostic and nerve conduction testing, the patient was diagnosed by her
      physician with right sterno-clavicular joint strain and scapular dyskinesis and
      was referred to physical therapy. Care was initiated based on this initial
      diagnosis. Upon further examination and perusal of the literature, the physical
      therapist proposed a diagnosis of spinal accessory nerve injury. Intervention
      included manual release of soft tissue tightness, neuromuscular facilitation and
      sport-specific strengthening, resulting in full return to functional and sport
      activities. These interventions focused on neurological re-education and muscular
      facilitation to address SANP as opposed to a joint sprain and dysfunction, as
      initially diagnosed. DISCUSSION: Proper diagnosis is imperative to effective
      treatment in all patients. This case illustrates the importance of a thorough
      examination and consideration of multiple diagnostic findings, particularly when
      EMG/NCV tests were negative, the cause was not apparent, and symptoms were less
      severe than other cases documented in the literature. LEVEL OF EVIDENCE:
      Diagnosis, level 4.

PMID- 21904700
TI  - Postactivation potentiation: an introduction.
AB  - Improving strength and power in the athlete who is being rehabilitated is a
      central focus of the sports physical therapist, particularly in the terminal
      phases of rehabilitation where the emphasis shifts to readiness to return to
      sport and sports performance enhancement. High load strength training and power
      training through plyometric exercises are two key components of performance
      enhancement programs. A current concept in the strength and conditioning
      literature that is relatively unknown in sports physical therapy is
      postactivation potentiation (PAP). Even though we have limited data and there may
      be limited application of the concept of PAP for the sports physical therapist,
      awareness of this phenomenon is important nonetheless. The purpose of this
      clinical commentary is to introduce the sports physical therapist to the concept
      of PAP.

PMID- 21904701
TI  - Integration of strength and conditioning principles into a rehabilitation
      program.
AB  - BACKGROUND AND PURPOSE: Rehabilitation and strength and conditioning are often
      seen as two separate entities in athletic injury recovery. Traditionally an
      athlete progresses from the rehabilitation environment under the care of a
      physical therapist and/or athletic trainer to the strength and conditioning coach
      for specific return to sport training. These two facets of return to sport are
      often considered to have separate goals. Initial goals of each are often
      different due to the timing of their implementation encompassing different stages
      of post-injury recovery. The initial focus of post injury rehabilitation includes
      alleviation of dysfunction, enhancement of tissue healing, and provision of a
      systematic progression of range-of-motion and strength. During the return to
      function phases, specific return to play goals are paramount. Understanding of
      specific principles and program parameters is necessary when designing and
      implementing an athlete's rehabilitation program. Communication and collaboration
      amongst all individuals caring for the athlete is a must. The purpose of this
      review is to outline the current evidence supporting utilization of training
      principles in athletic rehabilitation, as well as provide suggested
      implementation of such principles throughout different phases of a proposed
      rehabilitation program. EVIDENCE ACQUISITION: THE FOLLOWING ELECTRONIC DATABASES
      WERE USED TO IDENTIFY RESEARCH RELEVANT TO THIS CLINICAL COMMENTARY: MEDLINE
      (from 1950-June 2011) and CINAHL (1982-June 2011), for all relevant journal
      articles written in English. Additional references were accrued by independent
      searching of references from relevant articles. RESULTS: Currently evidence is
      lacking in the integration of strength and conditioning principles into the
      rehabilitation program for the injured athlete. Numerous methods are suggested
      for possible utilization by the clinician in practice to improve strength, power,
      speed, endurance, and metabolic capacity. CONCLUSION: Despite abundance of
      information on the implementation of training principles in the strength and
      conditioning field, investigation regarding the use of these principles in a
      properly designed rehabilitation program is lacking.

PMID- 21904702
TI  - The use of cardiopulmonary resuscitation and the automated external defibrillator
      in the practice of sports physical therapy.
AB  - During the initial assessment of the injured athlete, the Sports Physical
      Therapist (PT) must first be concerned with life-threatening emergencies such as
      absence of breathing and pulse. The sports PT must also be aware of the
      possibility of "sudden cardiac death" that could occur in others, including
      coaches, officials, and fans. If the PT assumes the role of "most medical" person
      at the contest or event, the responsibility for life saving action falls squarely
      on their shoulders. Therefore, skills and ongoing certification in cardio-
      pulmonary resuscitation techniques and the use of an automated external
      defibrillator are a basic necessity. These skills are required as part of the
      specialty practice of sports PT (BLS Healthcare Provider course or CPR for the
      Professional Rescuer in addition to completion of the First Responder Course OR
      credentials as an EMT or ATC), and are mandatory for being qualified to sit for
      the exam to become a sports certified specialist (SCS) by the American Board of
      Physical Therapy Specialties (ABPTS).(3).

PMID- 21904703
TI  - Strayed dogs sentinels of Trichinella britovi infection in Kosovo.

PMID- 21904704
TI  - Viewpoint: management of the patient with an 'incidentally' raised troponin.
AB  - Troponin assays are a valuable tool in early risk stratification of patients with
      ischaemic sounding chest pain. However, troponin is often measured outside of
      this clinical context. The finding of a raised troponin value may be
      misinterpreted as an acute coronary syndrome leading to unnecessary and sometimes
      dangerous anticoagulation. This article looks at some of the considerations which
      need to be made when interpreting the significance of a raised troponin value.

PMID- 21904705
TI  - The value of the Modified Early Warning Score and biochemical parameters as
      predictors of patient outcome in acute medical admissions a prospective study.
AB  - We evaluated the effectiveness of MEWS and biochemical parameters in predicting
      outcomes for acute medical admissions. Data from consecutive admissions to the
      Acute Medical Unit (AMU) of National Hospital of Sri Lanka were collected. C
      reactive protein (CRP), albumin, white cell count, platelet count and haemoglobin
      values were collected. Adverse endpoints were HDU/ICU admission,cardio
      respiratory emergency/resuscitation and death. A MEWS score of >=5 together with
      increasing age,pulse rate, respiratory rate, AVPU score, CRP,CRP/Albumin ratio
      and reduced platelet and albumin levelall increased the odds of reaching "adverse
      endpoints". Adding a score for biochemical parameters increased the area under
      the ROC curve for reaching "adverse endpoints" Biochemical parameters better
      predicted length of hospital stay and adverse outcomes. A combined scoring system
      improved the sensitivity of prediction.

PMID- 21904706
TI  - Teaching on the AMU ward round.
AB  - AMU ward rounds can be busy, and many consultants feel they are 'too busy to
      teach'. Yet the AMU is a rich learning environment. If we take the starting point
      that teaching is not the same as learning, how can consultants facilitate
      learning during a busy AMU ward round? Opportunistic teaching requires some
      planning but can easily be incorporated in to the business of the working day.
      Good educational practice requires some knowledge however. This article aims to
      give physicians some understanding and tips on teaching on the AMU ward round.

PMID- 21904708
TI  - An 'acute' presentation of motor neuron disease.
AB  - Motor neurone disease (MND) is a chronic condition which presents mainly in the
      seventh and eighth decades. It classically presents with a mixture of upper and
      lower motor neurone features, with a predilection for the limb muscles as the
      presenting feature. The case report outlined below describes acute respiratory
      failure requiring non invasive ventilation (NIV), at the time of diagnosis of
      MND. It highlights the need for the acute physician to be vigilant in the
      differing forms of presentation of this condition and its subsequent diagnosis
      and management.

PMID- 21904709
TI  - A case of haemophagocytic syndrome in HIV-associated disseminated histoplasmosis.
AB  - Disseminated histoplasmosis is an opportunistic infection which is commonly
      associated with HIV. Haemophagocytic lymphohistiocytosis (HLH) has been described
      as a secondary phenomenon to infection, collagen-vascular disorders and
      malignancies. In patients with HIV, cases of reactive haemophagocytic syndrome
      associated with disseminated histoplasmosis have been reported with CD4 counts of
      less than 50 cells/ul (450-1660 cells/ul). We report a case of a 25 year old man
      with HIV who presented with a CD4 count of 153 cells/ul and would suggest that
      this diagnosis should be considered at higher CD4 counts than previously
      reported.

PMID- 21904710
TI  - Acute fulminant necrotizing amoebic colitis: a potentially fatal cause of
      diarrhoea on the Acute Medical Unit.
AB  - Diarrhoea is a common presenting complaint to the Acute Medical Unit. We report a
      case of acute fulminant necrotizing amebic colitis in a 73 year old man with no
      recent travel history preceding his admission. Such cases are often difficult to
      diagnose and hence associated with a high mortality, unless treated promptly and
      appropriately. This case report highlights the importance of early diagnosis and
      prompt initiation of treatment.

PMID- 21904711
TI  - Acute medicine trainee update.

PMID- 21904713
TI  - Problem-based review: calcium channel blocker (CCB) poisoning.
AB  - A 56-year-old female presents to the emergency department 6h after taking an
      overdose of verapamil MR 120 mg * 28 capsules. She has a past medical history of
      hypertension and atrial flutter. On admission her GCS is 15, HR 50/min, BP
      100/64, Capillary blood glucose(CBG) 10.2. ECG shows sinus bradycardia with
      prolongation of the PR interval. You estimate her weight to be 60 kg.

PMID- 21904714
TI  - Problem-based review: self-harm and suicide risk.

PMID- 21904715
TI  - Balloon tamponade for variceal haemorrhage: a practical approach.
AB  - Balloon tamponade with compression tubes is used to stabilise life-threatening
      variceal bleeds when first-line endotherapy has failed and acts as a bridge to
      early definitive therapy. We present an overview of the use of compression tubes
      for variceal haemorrhage with a focus on insertion technique and aftercare.

PMID- 21904716
TI  - Picture quiz: a young man with palpitations. Wolff Parkinson White (WPW)
      syndrome.

PMID- 21904717
TI  - Contemporary definition of sepsis and the role of the Acute Medicine trainee in
      the management.

PMID- 21904723
TI  - New aspects of size-dependent metal-insulator transition in synthetic single
      domain monoclinic vanadium dioxide nanocrystals.
AB  - Nanoscale materials with size smaller than the characteristic domain size could
      simplify the domain structure and uncover the intrinsic properties in detail.
      Herein, a ultrafast open space calcination pathway is first put forward to
      synthesize high-quality single-domain VO(2)(M) nanocrystals and an in situ
      variable-temperature IR spectroscopy is first proposed to identify the size
      dependent MIT behaviors in VO(2)(M) below single-domain size. The variable
      temperature IR spectroscopy clearly reveals that these single-domain VO(2)(M)
      nanocrystals exhibit new size-dependent MIT behaviors, while the IR analysis
      further suggests that the size-related defect density and scattering efficiency
      could be used to account for their novel size-dependent MIT behaviors. This new
      characterization strategy of in situ variable-temperature IR spectroscopy holds
      great promise for extending to other systems to gain valuable insight into their
      intrinsic phase transition behaviors. Also, this ultrafast open space calcination
      pathway sets forth a new avenue in fabricating high-quality functional
      nanocrystals and paves the way for constructing intelligent nanodevices in the
      near future.

PMID- 21904724
TI  - Controlling the action of chlorine radical: from lab to environment.
AB  - The strength of Bz-Cl complexation has been explored using density functional
      theory (DFT) calculations, including dispersion-corrected (DFT-D) calculations.
      Of the methods tested, the omegaB97X-D method seems the best performing, along
      with the previously tested MPW1K method. The effect of substituent (X = NO(2), F,
      Cl, Br, H, CH(3), OCH(3), OH, NH(2) and N(CH(3))(2)) on the stabilities of the Ar
      Clpi-like intermediates show a good correlation with the linear free energy
      relationships used experimentally, but this is not the case for Ar-Clsigma
      complexes, suggesting the transition state of abstraction as being pi-like in
      nature. The role of PAH and lignin derivatives in mediating chlorination
      reactions in nature is explored. Stable pi-complexes were identified for lignin
      derivatives, indicating humic substances may mediate chlorine atom reactivity at
      the marine boundary layer, in addition to forming chlorolignins.

PMID- 21904726
TI  - Palladium containing periodic mesoporous organosilica with imidazolium framework
      (Pd@PMO-IL): an efficient and recyclable catalyst for the aerobic oxidation of
      alcohols.
AB  - The application of a novel palladium containing ionic liquid based periodic
      mesoporous organosilica (Pd@PMO-IL) catalyst in the aerobic oxidation of primary
      and secondary alcohols under molecular oxygen and air atmospheres is
      investigated. It was found that the catalyst is quite effective for the selective
      oxidation of several activated and non-activated alcoholic substrates. The
      catalyst system could be successfully recovered and reused several times without
      any significant decrease in activity and selectivity. Moreover, the hot
      filtration test, atomic absorption spectroscopy (AA) and kinetic study with and
      without selective catalyst poisons showed that the catalyst works in a
      heterogeneous pathway without any palladium leaching in reaction solution.
      Furthermore, nitrogen-sorption experiment and transmission electron microscopy
      (TEM) image proved the superior stability of high-ordered PMO-IL mesostructure
      during reaction process. TEM image also confirmed the presence of well
      distributed Pd-nanoparticles in the uniform mesochannels of the material. These
      observations can be attributed to the ionic liquid nature of PMO-IL mesostructure
      which facilitates the reaction through production, chemical immobilization and
      stabilization of active palladium nanoparticles, as well as preventing Pd
      agglomeration during overall process.

PMID- 21904727
TI  - pH-responsive self-duplex of (Py)A-substituted oligodeoxyadenylate in graphene
      oxide solution as a molecular switch.
AB  - In this paper, we demonstrated a highly discriminated and reliable molecular
      switch based on the interaction between the self-duplex of (Py)A-substituted
      oligodeoxyadenylate and graphene oxide in aqueous solution. This system showed a
      clear on/off state through the association and dissociation of (Py)A-modified
      oligodeoxynucleotide with graphene oxide in manipulated pH conditions, high
      amplitude efficiency for at least 50 cycles, and rapid response within seconds.
      Our molecular switch system has high reproducibility and simple operation by
      using pH stimulus.

PMID- 21904728
TI  - Detection of reverse transcription-PCR products by a simple and rapid light
      scattering technique.
AB  - A fast, sensitive and simple light scattering approach is developed to detect
      reverse transcription-PCR (RT-PCR) products. In the solution of HClO(4), the RT
      PCR products can be denatured and aggregated to form large particles, which can
      result in very strong light scattering. The RT-PCR products of D1/D2 domain in
      yeast 26S rRNA are successfully quantified with the proposed method. The light
      scattering intensity is well proportional to the concentration of RT-PCR products
      in the range of 0.01-0.5 MUg ml(-1) and 0.5-4.0 MUg ml(-1), respectively. The
      light scattering method gives more sensitive results, typically, two orders of
      magnitude better than agarose gel electrophoresis with ethidium bromide staining.
      The novel method has many advantages over conventional gel-based methods and
      other non-gel-based methods--fast detection within 5 min and stable signal within
      60 min, a simple detection system including only one cheap chemical agent
      (HClO(4)) and direct one-step detection without purification of the PCR reaction
      products--showing great potential in nucleic acid-based clinical diagnostics and
      other related fields.

PMID- 21904725
TI  - Restoration of taxonomic and functional genes after bioaugmentation of petroleum
      contaminated soil.
AB  - Soil microbial ecosystems are responsive to environmental changes that underpin
      the biological functions of the soil. The present study was conducted to profile
      variations in the microbial ecological system of remediated soil (R) and
      petroleum contaminated soil (P) based on comparisons with soil that had not been
      contaminated (N), using a cloning library of taxonomic genes (16S rRNA gene for
      bacteria and 18S rRNA gene for eukaryotes) and functional genes (nifH, amoA and
      narG). The results showed that N and R had a similar distribution in both the
      taxonomic genes and functional genes for bacteria and eukaryotes, which were
      dominated by Proteobacteria and Arthropoda, respectively. Phylogenetic analysis
      based on the nifH gene showed that the sequences from the three soils were
      clustered into six taxonomic groups, Actinobacteridae, and Alpha-, Beta-, Gamma-
      and Delta-proteobacteria, as well as an unclassified group. Evaluation of the
      amoA gene revealed that all sequences derived from the three samples belonged to
      Betaproteobacteria. The R and N soil had similar Shannon-Wiener diversity index
      (H') values, both of which were significantly higher than that of the P soil. The
      most abundant bacterial phylotype identified in the N and R soils were the same
      and were related to an uncultured bacterial clone (GAN-SB17, FN423475). None of
      the narG genes were found in the P soil. Similar results in terms of
      distribution, composition and the related index were obtained for nifH and amoA.
      These parameters may comprise a biological ecology index that may be applied to
      aid the design, implementation and evaluation of soil bioremediation.

PMID- 21904729
TI  - Chloro- and phenoxy-phosphines in frustrated Lewis pair additions to alkynes.
AB  - The reaction of tBu(C(6)H(4)O(2))P, with the borane B(C(6)F(5))(3) gives rise to
      NMR data consistent with the formation of the classical Lewis acid-base adduct
      tBu(C(6)H(4)O(2))P(B(C(6)F(5))(3)) (1). In contrast, the NMR data for the
      corresponding reactions of tBu(C(20)H(12)O(2))P and Cl(C(20)H(12)O(2))P with
      B(C(6)F(5))(3) were consistent with the presence of equilibria between free
      phosphine and borane and the corresponding adducts. Nonetheless, in each case,
      the adducts tBu(C(20)H(12)O(2))P(B(C(6)F(5))(3)) (2) and
      Cl(C(20)H(12)O(2))P(B(C(6)F(5))(3)) (3) were isolable. The species 1 reacts with
      PhCCH to give the new species tBu(C(6)H(4)O(2))P(Ph)C=CHB(C(6)F(5))(3) (4) in
      near quantitative yield. In an analogous fashion, the addition of PhCCH to
      solutions of the phosphines tBu(C(20)H(12)O(2))P, tBuPCl(2) and (C(6)H(3)(2,4
      tBu(2))O)(3)P each with an equivalent of B(C(6)F(5))(3) gave rise to
      L(Ph)C=CHB(C(6)F(5))(3) (L = tBu(C(20)H(12)O(2))P 5, tBuPCl(2)6 and (C(6)H(3)(2,4
      tBu(2))O)(3)P 7). X-Ray data for 1, 2, 6 and 7 are presented. The implications of
      these findings are considered.

PMID- 21904730
TI  - Highly effective copper-catalyzed decarboxylative coupling of aryl halides with
      alkynyl carboxylic acids.
AB  - We have developed a highly effective copper-catalyzed decarboxylative coupling of
      alkynylcarboxylic acids with various aryl and alkyl halides at 2 mol% loading of
      copper. This method is simple, economical and practical for the synthesis of
      disubstituted alkyne compounds.

PMID- 21904731
TI  - Self-assembled mesoporous Co and Ni-ferrite spherical clusters consisting of
      spinel nanocrystals prepared using a template-free approach.
AB  - Based on a self-assembly strategy, spherical mesoporous cobalt and nickel ferrite
      nanocrystal clusters with a large surface area and narrow size distribution were
      successfully synthesized for the first time via a template-free solvothermal
      process in ethylene glycol and subsequent heat treatment. In this work, the
      mesopores in the ferrite clusters were derived mainly from interior voids between
      aggregated primary nanoparticles (with crystallite size of less than 7 nm) and
      disordered particle packing domains. The concentration of sodium acetate is shown
      herein to play a crucial role in the formation of mesoporous ferrite spherical
      clusters. These ferrite clusters were characterized in detail using wide-angle X
      ray diffraction, thermogravimetric-differential thermal analysis, (57)Fe
      Mossbauer spectroscopy, X-ray photoelectron spectroscopy, field-emission scanning
      electron microscopy, standard and high-resolution transmission electron
      microscopy, and other techniques. The results confirmed the formation of both
      pure-phase ferrite clusters with highly crystalline spinel structure, uniform
      size (about 160 nm) and spherical morphology, and worm-like mesopore structures.
      The BET specific surface areas and mean pore sizes of the mesoporous Co and Ni
      ferrite clusters were as high as 160 m(2) g(-1) and 182 m(2) g(-1), and 7.91 nm
      and 6.87 nm, respectively. A model for the formation of the spherical clusters in
      our system is proposed on the basis of the results. The magnetic properties of
      both samples were investigated at 300 K, and it was found that these materials
      are superparamagnetic.

PMID- 21904732
TI  - Effect of antibody immobilization strategies on the analytical performance of a
      surface plasmon resonance-based immunoassay.
AB  - Antibody immobilization strategies (random, covalent, orientated and combinations
      of each) were examined to determine their performance in a surface plasmon
      resonance-based immunoassay using human fetuin A (HFA) as the model antigen
      system. The random antibody immobilization strategy selected was based on passive
      adsorption of anti-HFA antibody on 3-aminopropyltriethoxysilane (APTES)
      functionalized gold (Au) chips. The covalent strategy employed covalent
      crosslinking of anti-HFA antibody on APTES-functionalized chips using 1-ethyl-3
      [3-dimethylaminopropyl]carbodiimide (EDC) and sulfo-N-hydroxysuccinimide (SNHS).
      The orientation strategy used passive adsorption of protein A (PrA) on Au chips,
      with subsequent binding of the anti-HFA antibody in an orientated fashion via its
      fragment crystallisable (Fc) region. In the covalent-orientated strategy, PrA was
      first bound covalently, to the surface, which in turn, then binds the anti-HFA
      antibody in an orientated manner. Finally, in the most widely used strategy,
      covalent binding of anti-HFA antibody to carboxymethyldextran (CM5-dextran) was
      employed. This immobilization strategy gave the highest anti-HFA antibody
      immobilization density, whereas the highest HFA response was obtained with the
      covalent-orientated immobilization strategy. Therefore, the covalent-orientated
      strategy was the best for SPR-based HFA immunoassay and can detect 0.6-20.0 ng/mL
      of HFA in less than 10 min.

PMID- 21904733
TI  - Preparation of oligosaccharides by homogenous enzymatic synthesis and solid phase
      extraction.
AB  - This communication describes a method for enzymatic preparation of bioactive
      glycans, which integrated the high-efficiency of homogenous phase enzymatic
      reaction and fast separation of solid phase extraction.

PMID- 21904734
TI  - Homolytic molecular dissociation in natural orbital functional theory.
AB  - The dissociation of diatomic molecules of the 14-electron isoelectronic series
      N(2), O(2)(2+), CO, CN(-) and NO(+) is examined using the Piris natural orbital
      functional. It is found that the method describes correctly the dissociation
      limit yielding an integer number of electrons on the dissociated atoms, in
      contrast to the fractional charges obtained when using the variational two
      particle reduced density matrix method under the D, Q and G positivity necessary
      N-representability conditions. The chemistry of the considered systems is
      discussed in terms of their dipole moments, natural orbital occupations and bond
      orders as well as atomic Mulliken populations at the dissociation limit. The
      values obtained agree well with accurate multiconfigurational wave function based
      CASSCF results and the available experimental data.

PMID- 21904735
TI  - Bi2S3 nanomaterials: morphology manipulation and related properties.
AB  - The Bi(2)S(3) nanomaterials with various morphologies such as nanorods,
      nanowires, nanowire bundles, urchin-like microspheres and urchin-like
      microspheres with cavities have been successfully synthesized through a simple
      hydrothermal method. Experimental results indicate that sulfur sources play
      crucial roles in determining the morphologies of Bi(2)S(3) products. Moreover,
      formation mechanisms of different Bi(2)S(3) nanostructures are discussed based on
      understanding of the growth habit of Bi(2)S(3) crystal. Finally, we also studied
      the morphologies-dependent electrochemical and optical properties of the as
      synthesized Bi(2)S(3) nanomaterials.

PMID- 21904736
TI  - Chiral organoselenium-transition-metal catalysts in asymmetric transformations.
AB  - In recent years, there has been an increasing application of chiral selenium
      compounds as ligands in metal-catalyzed enantioselective transformations. One of
      the most important challenges in this field is the development of new chiral
      complexes (catalyst) generated from the reaction between a metal and appropriate
      chiral selenium-containing compounds (ligand). The vast majority of these ligands
      are easily synthesized in a few high-yielding synthetic steps, starting from
      readily available chiral amino alcohols. In this context, the advantages of using
      these compounds will be discussed, mainly with regard to their easy
      accessibility, modular nature and the formation of strong bonds with soft or,
      more rarely, hard metals. Important selective contributions within the field of
      chiral selenium complexes are examined, according to their applications. As final
      remarks, future developments and perspectives of the field are discussed.

PMID- 21904737
TI  - Carbene-stabilized main group diatomic allotropes.
AB  - While transition metals are well known for assuming the formal oxidation state of
      zero in various compounds main group elements have rarely engaged in this
      practice. Recent reports of N-heterocyclic carbene-stabilized main group diatomic
      allotropes (i.e., Si(2), Ge(2), P(2), As(2)) denote a breakthrough of zero
      oxidation state main group chemistry. This Perspective addresses the synthesis
      and characterization of these highly reactive main group molecules, with a
      particular emphasis on the very recent progress in the reactivity study of
      carbene-stabilized Si(2) and P(2).

PMID- 21904738
TI  - Whole-cell bacterial biosensors for rapid and effective monitoring of heavy
      metals and inorganic pollutants in wastewater.
AB  - The increasing number of potentially harmful pollutants in the wastewater
      effluent discharge necessitates the need for the development of fast and cost
      effective analytical techniques for extensive monitoring programmes to assess the
      effectiveness of the treatment process. This study compared the use of bacterial
      biosensors to the conventional Daphnia magna assay, Chemical Oxygen Demand (COD)
      and Biochemical Oxygen Demand (BOD) tests as well as chemical analysis, for
      monitoring the toxicity of wastewater. The bacterial biosensors constructed in
      this study, using S. sonnei and E. coli, were found to be sensitive to the
      toxicity of the wastewater effluents. A linear increase in bioluminescence with
      increasing concentration of heavy metals and inorganic pollutants in water was
      observed, with a correlation coefficient (r(2)) as high as 0.995 and 0.997,
      respectively. No notable correlation between biosensor toxicity and BOD and COD
      test results was observed. These bacterial biosensors could provide appropriate
      alternatives for a rapid, sensitive and cost effective detection of wastewater
      quality. However, the differences in sensitivity obtained for the different
      systems suggest that the use of a battery of toxicity assays may be required to
      provide a real ecotoxicological assessment of wastewater samples.

PMID- 21904740
TI  - DNA discrete modified gold nanoparticles.
AB  - Recently, controlling assembly process in a precise manner has attracted
      increasing attentions in nanofabrication. Gold nanoparticles (AuNPs) modified
      with countable number of DNA strands, i.e., DNA discrete modified AuNPs, which
      bring AuNPs much more controllable manipulating possibilities have been playing
      an important role in this field. In this feature article, we will summarize
      recent progress on their preparation strategies and application in positioning
      assembly, which could benefit to the improvement of preparation methods of DNA
      discrete modified AuNPs and even other nanoparticles.

PMID- 21904741
TI  - UVA filters in sun-protection products: regulatory and biological aspects.
AB  - This review of published in vitro and in vivo studies concerning the biological
      effects of ultraviolet A (UVA; 320-400 nm) radiation illustrates the evidence for
      combining UVA and UVB filters in sun-protection products. These data have led to
      the development of new sunscreens as well as methods to evaluate their efficacy.
      After listing the UVA filters available and briefly noting the requirements for a
      high SPF, broad-spectrum sunscreen, the methods for evaluating the level of UVA
      protection will be described. This article also summarizes several studies
      looking at the prevention of erythema, pigmentation, DNA damage,
      photoimmunosuppression, photoaging and photodermatoses. These data demonstrate in
      vitro and in vivo that only well-balanced UVA-UVB sunscreens, absorbing over the
      entire UV spectrum are able to prevent or significantly reduce the associated
      biological damage.

PMID- 21904742
TI  - MEMS microwell and microcolumn arrays: novel methods for high-throughput cell
      based assays.
AB  - Although the cell-based assay is becoming more popular for high throughput drug
      screening and the functional characterization of disease-associated genes, most
      researchers in these areas do not use it because it is a complex and expensive
      process. We wanted to create a simple method of performing an on-chip cell-based
      assay. To do this, we used micro-electro-mechanical systems (MEMS) to fabricate a
      microwell array chip comprised of a glass substrate covered with a photoresist
      film patterned to form multiple microwells and tested it in two reverse
      transfection experiments, an exogenous gene expression study and an endogenous
      gene knockdown study. It was used effectively in both. Then, using the same MEMS
      technology, we fabricated a complementary microcolumn array to be used as a drug
      carrier device to topically apply drugs to cells cultured in the microwell array.
      We tested the effectiveness of microwell-microcolumn on-chip cell-based assay by
      using it in experiments to identify epidermal growth factor receptor (EGFR)
      activity inhibitors, for which it was found to provide effective high throughput
      and high content functional screening. In conclusion, this new method of cell
      based screening proved to be a simple and efficient method of characterizing gene
      function and discovering drug leads.

PMID- 21904744
TI  - Coordination driven axial chirality in a microporous solid assembled from an
      achiral linker via in situ C-N coupling.
AB  - Metal mediated in situ C-N coupling between 4,4'-azobipyridine and disodium-trans
      glutaconate at room temperature has formed a new multifunctional linker Z-dhpe
      which subsequently self-assembles with Zn(II) or Cd(II) resulting in a chiral or
      an achiral metal-organic framework, respectively, depending on its different
      coordination modes.

PMID- 21904743
TI  - Towards models of the oxygen-evolving complex (OEC) of photosystem II: a Mn4Ca
      cluster of relevance to low oxidation states of the OEC.
AB  - Synthetic access has been achieved into high oxidation state Mn/Ca chemistry with
      the 4 : 1 Mn : Ca stoichiometry of the oxygen-evolving complex (OEC) of plants
      and cyanobacteria; the anion of (Et(3)NH)(2)[Mn(III)(4)Ca(O(2)CPh)(4)(shi)(4)]
      has a square pyramidal metal topology and an S = 0 ground state.

PMID- 21904745
TI  - A modular molecular photovoltaic system based on phospholipid/alkanethiol hybrid
      bilayers: photocurrent generation and modulation.
AB  - Monolayer quantities of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC),
      incorporated with either fullerenes or ruthenium tris(bipyridyl) (Ru(bpy)(3)(2+))
      complexes, were formed on ferrocene-terminated C11-alkanethiol self-assembled
      monolayers (SAMs) through lipid fusion. Thus formed hybrid structures are
      characterized by quartz crystal microbalance, UV-vis spectroscopy, cyclic
      voltammetry and impedance analysis. In comparison to lipid monolayers deposited
      on C12-alkanethiol SAMs, photocurrent generation from these ferrocene-based
      structures is significantly modulated, displaying attenuated anodic photocurrents
      and enhanced cathodic photocurrents. While a similar trend was observed for the
      two photoagents studied, the degree of such modulations was always found to be
      greater in fullerene-incorporated bilayers. These findings are evaluated in the
      context of the film structure, energetics of the involved photo(electrochemical)
      species and cross-membrane electron-transfer processes.

PMID- 21904746
TI  - Chiral salen-metal derivatives of polyoxometalates with asymmetric catalytic and
      photocatalytic activities.
AB  - Immobilization of the chiral salen-metal complex [Mn(III)(salen)(H(2)O)(2)ClO(4)]
      on the Keggin-type polyoxometalate (POM) skeletons leads to the isolation of POM
      derivatives functionalized with chiral salen-metal complexes, which represent the
      first examples of introducing chiral salen-metal complexes into the POM systems.

PMID- 21904747
TI  - Spontaneous symmetry breaking in a non-rigid molecule approach to intrinsically
      disordered proteins.
AB  - An analog to Longuet-Higgins' non-rigid molecular group theory arguments can be
      applied to the structure and reaction dynamics of intrinsically disordered
      proteins via a somewhat counterintuitive Morse Function treatment inspired by
      statistical mechanics, providing possible symmetry classifications of the
      molecular 'fuzzy lock-and-key'.

PMID- 21904748
TI  - Metal retention in human transferrin: consequences of solvent composition in
      analytical sample preparation methods.
AB  - The analysis of metal-binding proteins requires careful sample manipulation to
      ensure that the metal-protein complex remains in its native state and the metal
      retention is preserved during sample preparation or analysis. Chemical analysis
      for the metal content in proteins typically involves some type of liquid
      chromatography/electrophoresis separation step coupled with an atomic (i.e.,
      inductively coupled plasma-optical emission spectroscopy or -mass spectrometry)
      or molecular (i.e., electrospray ionization-mass spectrometry) analysis step that
      requires altered-solvent introduction techniques. UV-VIS absorbance is employed
      here to monitor the iron content in human holo-transferrin (Tf) under various
      solvent conditions, changing polarity, pH, ionic strength, and the ionic and
      hydrophobic environment of the protein. Iron loading percentages (i.e. 100%
      loading equates to 2 Fe(3+):1 Tf) were quantitatively determined to evaluate the
      effect of solvent composition on the retention of Fe(3+) in Tf. Maximum retention
      of Fe(3+) was found in buffered (20 mM Tris) solutions (96 +/- 1%). Exposure to
      organic solvents and deionized H(2)O caused release of ~23-36% of the Fe(3+) from
      the binding pocket(s) at physiological pH (7.4). Salt concentrations similar to
      separation conditions used for ion exchange had little to no effect on Fe(3+)
      retention in holo-Tf. Unsurprisingly, changes in ionic strength caused by
      additions of guanidine HCl (0-10 M) to holo-Tf resulted in unfolding of the
      protein and loss of Fe(3+) from Tf; however, denaturing and metal loss was found
      not to be an instantaneous process for additions of 1-5 M guanidinium to Tf. In
      contrast, complete denaturing and loss of Fe(3+) was instantaneous with >=6 M
      additions of guanidinium, and denaturing and loss of iron from Tf occurred in
      parallel proportions. Changes to the hydrophobicity of Tf (via addition of 0-14 M
      urea) had less effect on denaturing and release of Fe(3+) from the Tf binding
      pocket compared to changes in ionic strength.

PMID- 21904749
TI  - Facile synthesis of two-dimensional graphene/SnO2 /Pt ternary hybrid
      nanomaterials and their catalytic properties.
AB  - In this paper, we reported a simple, aqueous-phase route to the synthesis of two
      dimensional graphene/SnO(2) composite nanosheets (GSCN) hybrid nanostructures
      consisting of 5 nm Pt nanoparticles supported on the both sides of GSCN.
      Functional two-dimensional GSCN were obtained through the reduction of graphene
      oxide (GO) using SnCl(2) in the presence of polyelectrolyte
      poly(diallyldimethylammonium chloride) (PDDA). The main advantages of this
      preparation are that the reduction of GO, the formation of SnO(2) and the
      functionalization of GSCN were achieved simultaneously through one-pot reaction.
      GSCN/Pt ternary hybrid nanomaterials were generated by in situ reduction of
      negatively charged PtCl(6)(2-) precursors adsorbed on the positively charged
      surface of GSCN through electrostatic attraction. The as-synthesized GSCN/Pt
      ternary hybrid nanomaterials exhibited high cycle stabilization during the
      catalytic reduction of p-nitrophenol into p-aminophenol by NaBH(4). Additionally,
      our approach is expected to extend to other hybrid nanomaterials. We believe that
      the obtained GSCN/Pt ternary hybrid nanomaterials have great potential for
      applications in other field, such as electrochemical energy storage, sensors, and
      so on.

PMID- 21904750
TI  - Two-dimensional single-crystalline Zn hexagonal nanoplates: size-controllable
      synthesis and X-ray diffraction study.
AB  - We synthesized two-dimensional (2D) Zn hexagonal nanoplates using the thermal
      metal-vapor deposition technique. An increase and decrease in the surface area
      and thickness of the 2D Zn hexagonal nanoplates were shown with elevated
      annealing temperatures, indicating their sizes to be controlled using the
      annealing treatment. X-Ray diffractometry (XRD) studies revealed the crystalline
      nature of the 2D Zn hexagonal nanoplates and the diffraction intensity of the
      (002) lattice plane, which increased parabolically with elevated annealing
      temperatures.

PMID- 21904751
TI  - Dual modal in vivo imaging using upconversion luminescence and enhanced computed
      tomography properties.
AB  - In vivo upconversion luminescence (UCL) imaging, exhibiting favorable
      characteristics such as high photostability, no blinking, sharp emission lines,
      and long lifetimes, is recognized as the excellent and significant
      photoluminescence imaging for the future. To develop the imaging system with high
      visual sensitivity and tissue penetration, the functional molecules with X-ray
      computed tomography (CT) contrast were grafted onto upconversion nanoparticles to
      obtain beta-NaYF(4):18% Yb(3+),2%Er(3+)@SiO(2)-I/PEG (UCNPs@SiO(2)-I/PEG)
      nanoprobes. These nanoprobes are water-soluble, have low cytotoxicity, and
      possess excellent UCL and remarkable CT contrast. Of particular note is that,
      besides the element iodine, rare earth elements (Y, Yb, and Er) present in the
      nanoprobes also show CT contrast. Moreover, no background autofluorescence signal
      is found in in vivo UCL images. We believe that these nanoprobes with dual modal
      in vivo imaging of UCL and CT can serve as a promising platform for clinical
      diagnosis or biomedical studies.

PMID- 21904752
TI  - A facile and sensitive immunoassay for the detection of alpha-fetoprotein using
      gold-coated magnetic nanoparticle clusters and dynamic light scattering.
AB  - A facile and sensitive immunoassay protocol for the detection of alpha
      fetoprotein (AFP) was developed using gold-coated iron oxide magnetic
      nanoclusters and dynamic light scattering (DLS) methods. The increase in the
      average particle size due to AFP-mediated aggregation was measured using DLS, and
      the detection limit was better than 0.01 ng mL(-1).

PMID- 21904754
TI  - Tuning of spin crossover behaviour in iron(III) complexes involving pentadentate
      Schiff bases and pseudohalides.
AB  - Investigations on a series of eight novel mononuclear iron(III) Schiff base
      complexes with the general formula [Fe(L(5))(L(1))].S (where H(2)L(5) =
      pentadentate Schiff-base ligand, L(1) = a pseudohalido ligand, and S is a solvent
      molecule) are reported. Several different aromatic 2-hydroxyaldehyde derivatives
      were used in combination with a non-symmetrical triamine 1,6-diamino-4-azahexane
      to synthesize the H(2)L(5) Schiff base ligands. The consecutive reaction with
      iron(III) chloride resulted in the preparation of the [Fe(L(5))Cl] precursor
      complexes which were left to react with a wide range of the L(1) pseudohalido
      ligands. The low-spin compounds were prepared using the cyanido ligand: [Fe(3m
      salpet)(CN)].CH(3)OH (1a), [Fe(3e-salpet)(CN)].H(2)O (1b), while the high-spin
      compounds were obtained by the reaction of the pseudohalido (other than cyanido)
      ligands with the [Fe(L(5))Cl] complex arising from salicylaldehyde derivatives:
      [Fe(3Bu5Me-salpet)(NCS)] (2a), [Fe(3m-salpet)(NCO)].CH(3)OH (2b) and [Fe(3m
      salpet)(N(3))] (2c). The compounds exhibiting spin-crossover phenomena were
      prepared only when L(5) arose from 2-hydroxy-1-naphthaldehyde (H(2)L(5) =
      H(2)napet): [Fe(napet)(NCS)].CH(3)CN (3a, T(1/2) = 151 K),
      [Fe(napet)(NCSe)].CH(3)CN (3b, T(1/2) = 170 K), [Fe(napet)(NCO)] (3c, T(1/2) =
      155 K) and [Fe(napet)(N(3))], which, moreover, exhibits thermal hysteresis (3d,
      T(1/2)? = 122 K, T(1/2)? = 117 K). These compounds are the first examples of
      octahedral iron(III) spin-crossover compounds with the coordinated pseudohalides.
      We report the structure and magnetic properties of these complexes. The magnetic
      data of all the compounds were analysed using the spin Hamiltonian formalism
      including the ZFS term and in the case of spin-crossover, the Ising-like model
      was also applied.

PMID- 21904753
TI  - Calix[4]arene-supported rare earth octahedra.
AB  - A series of calix[4]arene-supported Ln(III)(6) clusters have been synthesised
      under facile bench top conditions. The magnetic and structural properties of
      these clusters are reported, the latter suggesting that the Ln(III)-calix[4]arene
      moiety may be used for the construction of other assemblies in a manner akin to
      that for the Mn(III)-calix[4]arene analogue.

PMID- 21904755
TI  - Nuclear translocation of NF-kappaB in intact human gut tissue upon stimulation
      with coffee and roasting products.
AB  - In the healthy gut, NF-kappaB is a critical factor of the intestinal immune
      system, whereas inflammatory bowel diseases are associated with chronic
      activation of NF-kappaB. Previous studies indicated that coffee induces nuclear
      translocation of NF-kappaB in macrophages, an effect attributed to roasting
      products. In the present work, coffee extract or roasting products induced
      nuclear translocation of NF-kappaB in macrophages, Caco-2 cells, and primary
      human intestinal microvascular endothelial cells (up to fivefold, p<0.001). Since
      the effect clearly depended on the cell type, ex vivo experiments were performed
      with intact human gut tissue from biopsies. The uniformity of the specimens and
      tissue viability during ex vivo incubation for up to 2 h were verified. Roasting
      products led to a concentration dependent significant increase of nuclear
      translocation of NF-kappaB in human gut tissue (up to 2.85 fold increase,
      p=0.0321), whereas coffee extract induced a trend towards higher nuclear NF
      kappaB concentration. NF-kappaB activation in macrophages and Caco-2 cells by
      roasting products was significantly blocked by co-incubation with catalase
      (p=0.011 and p=0.024) indicating involvement of H(2)O(2)-signaling. Monitoring of
      extracellular H(2)O(2) indicated that roasting products in coffee constantly
      generate H(2)O(2) by spontaneous oxygen reduction, which is only partially
      detoxified by cellular antioxidative systems. Thus, it can be concluded that ex
      vivo stimulation of intact human gut tissue is a valuable model to study
      nutritional effects on complex tissue systems. Furthermore, the consumption of
      coffee and roasting products may be able to induce nuclear NF-kappaB
      translocation in the human gut.

PMID- 21904756
TI  - Organic-based molecular switches for molecular electronics.
AB  - In a general sense, molecular electronics (ME) is the branch of nanotechnology
      which studies the application of molecular building blocks for the fabrication of
      electronic components. Among the different types of molecules, organic compounds
      have been revealed as promising candidates for ME, due to the easy access, great
      structural diversity and suitable electronic and mechanical properties. Thanks to
      these useful capabilities, organic molecules have been used to emulate electronic
      devices at the nanoscopic scale. In this feature article, we present the diverse
      strategies used to develop organic switches towards ME with special attention to
      non-volatile systems.

PMID- 21904757
TI  - A molecular dynamics study of the mechanical properties of graphene nanoribbon
      embedded gold composites.
AB  - Molecular dynamics simulations were performed to investigate the mechanical
      properties of a single-crystal gold nanosheet and graphene nanoribbon-embedded
      gold (GNR/Au) composites for various embedded locations, temperatures, and
      lengths. The computational results show that the Young's modulus, tensile
      strength, and fracture strain of GNR/Au composites are much larger than those of
      pure gold. The mechanical properties of GNR/Au composites deteriorate drastically
      due to C-C bond breaking. Thermal fluctuation and an increase in length can
      decrease the mechanical properties of GNR/Au composites.

PMID- 21904758
TI  - Multivalent interaction and selectivities in selectin binding of functionalized
      gold colloids decorated with carbohydrate mimetics.
AB  - Colloidal gold particles with functionalized organic shells were applied as novel
      selectin binders. The ligand shell was terminated with different monocyclic
      carbohydrate mimetics as simplified analogs of the sLe(x) unit found in
      biological selectin ligands. The multivalent presentation of the sulfated
      selectin binding epitopes on the gold particles led to extremely high binding
      affinities towards L- and P-selectin and IC(50) values in the subnanomolar range.
      Depending on the ring size of the sulfated carbohydrate mimetic, its substitution
      pattern and its configuration, different selectivities for either L-selectin or P
      selectin were obtained. These selectivities were not found for gold particles
      with simple acyclic sulfated alcohols, diols and triols in the ligand shell. In
      addition, the influence of the particle size and the thickness of the hydrophobic
      organic shell were systematically investigated.

PMID- 21904759
TI  - Nonheme ferric hydroperoxo intermediates are efficient oxidants of bromide
      oxidation.
AB  - This work presents the first combined experimental and computational study that
      gives evidence of the electrophilic reactivity of a nonheme iron(III)-hydroperoxo
      species. We show that in contrast to their heme counterparts the nonheme
      iron(III)-hydroperoxo complexes are catalytically much more active and even more
      so than nonheme iron(IV)-oxo species.

PMID- 21904760
TI  - Noncovalent interaction of polyethylene glycol with copper complex of
      ethylenediaminetetraacetic acid and its application in constructing inorganic
      nanomaterials.
AB  - In this study, we try to answer a fundamental question: what is the consequence
      of the noncovalent interaction between a polymer and a coordination compound?
      Here, polyethylene glycol (PEG-4000, PEG-b) and copper complex of
      ethylenediaminetetraacetic acid (H(2)CuY) were employed to solve this problem. A
      novel adduct (CEP) between H(2)CuY and PEG-b was prepared. Our results indicated
      several interesting findings. First, the introduction of H(2)CuY had no effect on
      the stacking structure of PEG-b but led to a large change in surface structure of
      the polymer. Second, there was a significant difference (117 K) in the maximum
      degradation temperature between the PEG and the CEP, suggesting that the
      noncovalent interaction can drastically improve the thermal stability of the PEG.
      Third, sintering experiments showed that H(2)CuY and CEP produced completely
      different decomposition products. The former formed Cu crystals in nitrogen and
      CuO in air, but the latter generated Cu and CuCl crystals with good
      crystallinity, respectively. Finally, three independent measurements: viscosity,
      conductivity and nuclear magnetic resonance in solution, provided useful
      information and insights from both sides of the noncovalent interaction. Probable
      interaction mechanisms and interaction sites were proposed. We consider that the
      current research could create the foundation for a new understanding of how the
      noncovalent adduct interaction between a metallic complex and a polymer relates
      to the change in physical and chemical properties of the adducted components.

PMID- 21904761
TI  - The chemistry and biology of syringolins, glidobactins and cepafungins
      (syrbactins).
AB  - Syrbactin is a subordinate term for the syringolin, glidobactin and cepafungin
      natural product families. Their grouping is based on their related molecular
      frameworks, similar biosynthesis pathways and, most importantly, identical modes
      of-action, being irreversible proteasome inhibition. With this report, we aim to
      review their chemical biology, describing their common, but also differential
      characteristics.

PMID- 21904762
TI  - Surface modified electrospun poly(vinyl alcohol) membranes for extracting
      nanoparticles from water.
AB  - Contamination of water from nanomaterials will be an emerging problem in the
      future due to incorporation of nanomaterials in many commercial products and
      improper disposal of waste materials. In this report, electrospun polyvinyl
      alcohol nanofibers (PVA NFs) with diameters ranging between 300 and 500 nm were
      used for the extraction of nanosized contaminants from the aqueous environment.
      To obtain the best extraction efficiency, surface hydroxyl groups of PVA NFs were
      chemically modified with functional groups, such as thiols and amines. Two model
      nanoparticles (silver and gold) dissolved in water were used for adsorption
      studies. Depending on the nature of the surface functionalities, the fibers
      showed unique ability to adsorb nanoparticles. The extraction studies revealed
      that the amine and thiol modified PVA NFs showed 90% extraction efficiency for
      both silver and gold nanoparticles. The thiol and amine functionalized PVA NFs
      showed maximum adsorption capacities (Q(t)) towards Au NPs, which were around 79
      84 mg g(-1). Similarly for Ag NP extraction, amine functionalized PVA NFs showed
      a value for Q(t) at 56 mg g(-1). Our results highlight that functionalized
      nanofibers have high extraction efficiency for dissolved nanoparticles in water
      and can be used for removal of the nanocontaminants from the aqueous environment.

PMID- 21904763
TI  - Rapid, in situ synthesis of bidentate ligands: chromatography-free generation of
      catalyst libraries.
AB  - The parallel synthesis of chiral bidentate ligands and their subsequent use in
      situ for a catalytic process is described. The ligands thus prepared gave
      comparable results to those obtained when the ligands were synthesized and
      purified by conventional means. This includes oxazolines and other compounds of
      similar complexity, meaning that for the first time these valuable compounds have
      been brought into the field of combinatorial catalysis.

PMID- 21904767
TI  - Can an eight pi-electron bare ring be planar?
AB  - Here we explore in silico an alternative to make planar eight pi-electron bare
      ring systems with substitutions of some cyclooctatetraene ring carbon atoms by
      heavier group 14 elements. We found that the most stable eight membered rings
      with formulae C(4)Si(4)H(8), C(4)Ge(4)H(8), and C(4)Sn(4)H(8) have a perfect
      planar structure, enhancing delocalization energy as compared to cot.

PMID- 21904768
TI  - Thiolato gold(I) complexes containing water-soluble phosphane ligands: a
      characterization of their chemical and biological properties.
AB  - A series of thiolate gold(I) derivatives bearing water soluble phosphanes--namely
      sodium triphenylphosphane monosulfonate (TPPMS), sodium triphenylphosphane
      trisulfonate (TPPTS), 1,3,5-triaza-7-phosphaadamantane (PTA) and 3,7-diacetyl
      1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane (DAPTA)--is reported and the compounds
      studied for their luminescence properties in the solid state. Two of these
      derivatives, [Au(SMe(2)pyrim)(PTA)] and [Au(SBenzoxazole)(DAPTA)], are also
      structurally characterized by X-ray diffraction analysis. Strong
      antiproliferative effects are observed for most of the compounds in the human
      ovarian carcinoma cell lines (A2780/S) and its cisplatin-resistant variant
      (A2780/R), which depend on both the type of thiolate and phosphane ligands. ICP
      MS studies were also performed to evaluate the influence of the gold uptake on
      the cytotoxic potency of the compounds.

PMID- 21904769
TI  - The effect of peripheral bipyridine ligands on the photocatalytic hydrogen
      production activity of Ru/Pd catalysts.
AB  - A pyrazine bridged ruthenium/palladium bimetallic photocatalyst with peripheral
      4,4'-dicarboxyethyl-2,2'-bipyridine ligands, EtOOC-RuPd, is reported, together
      with its 2,2'-bipyridine analogue. Upon irradiation with visible light, EtOOC
      RuPd catalyses the production of hydrogen gas whereas the complex RuPd does not.

PMID- 21904770
TI  - An independent review and prioritization of past radionuclide and chemical
      releases from the Los Alamos National Laboratory--implications for future dose
      reconstruction studies.
AB  - From 1999 through 2010, a team of scientists and engineers systematically
      reviewed approximately eight million classified and unclassified documents at Los
      Alamos National Laboratory (LANL) that describe historical off-site releases of
      radionuclides and chemicals in order to determine the extent to which a full
      scale dose reconstruction for releases is warranted and/or feasible. As a part of
      this effort, a relative ranking of historical airborne and waterborne
      radionuclide releases from LANL was established using priority index (PI) values
      that were calculated from estimated annual quantities released and the maximum
      allowable effluent concentrations according to The U.S. Nuclear Regulatory
      Commission (USNRC). Chemical releases were ranked based on annual usage estimates
      and U.S. Environmental Protection Agency (USEPA) toxicity values. PI results for
      airborne radionuclides indicate that early plutonium operations were of most
      concern between 1948 and 1961, in 1967, and again from 1970 through 1973.
      Airborne releases of uranium were found to be of most interest for 1968, from
      1974 through 1978, and again in 1996. Mixed fission products yielded the highest
      PI value for 1969. Mixed activation product releases yielded the highest PI
      values from 1979 to 1995. For waterborne releases, results indicate that
      plutonium is of most concern for all years evaluated with the exception of 1956
      when (90)Sr yielded the highest PI value. The prioritization of chemical releases
      indicate that four of the top five ranked chemicals were organic solvents that
      were commonly used in chemical processing and for cleaning. Trichloroethylene
      ranked highest, indicating highest relative potential for health effects, for
      both cancer and non-cancer effects. Documents also indicate that beryllium was
      used in significant quantities, which could have lead to residential exposures
      exceeding established environmental and occupational exposure limits, and
      warrants further consideration. In part because of the close proximity of
      residents to LANL, further study of historical LANL releases and the potential
      impact to public health is recommended for those materials with the largest
      priority index values; namely, plutonium, uranium, and selected chemicals.

PMID- 21904771
TI  - Chimeric GNA/DNA metal-mediated base pairs.
AB  - DNA double helices comprising chimeric GNA/DNA metal-mediated base pairs have
      been synthesized and characterized (GNA = glycol nucleic acid). The possibility
      to combine different nucleic acid backbones within one metal-mediated base pair
      expands the applicability of metal-functionalized nucleic acids.

PMID- 21904772
TI  - Photo-driven anti-Markovnikov alkyne hydration in self-assembled hollow
      complexes.
AB  - Under UV-light irradiation, the anti-Markovnikov hydration of internal
      arylalkynes proceeds in the cavity of an electron-deficient coordination cage to
      give benzyl ketones; the reaction is triggered by cage-mediated, photo-induced
      electron transfer from the alkynes to the cage.

PMID- 21904773
TI  - Exosomes from breast cancer cells can convert adipose tissue-derived mesenchymal
      stem cells into myofibroblast-like cells.
AB  - Exosomes are small membrane vesicles secreted into the extracellular environment
      by various types of cells, including tumor cells. Exosomes are enriched with a
      discrete set of cellular proteins, and therefore expected to exert diverse
      biological functions according to cell origin. Mesenchymal stem cells (MSCs)
      possess the potential for differentiation into multilineages and can also
      function as precursors for tumor stroma including myofibroblast that provides a
      favorable environment for tumor progression. Although a close relationship
      between tumor cells and MSCs in a neoplastic tumor microenvironment has already
      been revealed, how this communication works is poorly understood. In this study,
      we investigated the influence of tumor cell-derived exosomes on MSCs by treating
      adipose tissue-derived MSCs (ADSCs) with breast cancer-derived exosomes. The
      exosome-treated ADSCs exhibited the phenotypes of tumor-associated myofibroblasts
      with increased expression of alpha-SMA. Exosome treatment also induced increased
      expression of tumor-promoting factors SDF-1, VEGF, CCL5 and TGFbeta. This
      phenomenon was correlated with increased expression of TGFbeta receptor I and II.
      Analysis of SMAD2, a key player in the TGFbeta receptor-mediated SMAD pathway,
      revealed that its phosphorylation was increased by exosome treatment and was
      inhibited by treatment with SB431542, an inhibitor of the SMAD-mediated pathway,
      resulting in decreased expression of alpha-SMA. Taken together, our results show
      that tumor-derived exosomes induced the myofibroblastic phenotype and
      functionality in ADSCs via the SMAD-mediated signaling pathway. In conclusion,
      this study suggests that tumor-derived exosomes can contribute to progression and
      malignancy of tumor cells by converting MSCs within tumor stroma into tumor
      associated myofibroblasts in the tumor microenvironment.

PMID- 21904774
TI  - Risk factors for epithelial ovarian cancer in Japan - results from the Japan
      Public Health Center-based Prospective Study cohort.
AB  - The aim of this study was to evaluate the risk factors for invasive primary
      epithelial ovarian cancer among Japanese women. In 1990-1994, 45,748 women aged
      40-69 years were enrolled in the Japan Public Health Center-based Prospective
      Study cohort. Only 86 epithelial ovarian cancer cases were diagnosed during
      follow-up through 2008, reflecting the low ovarian cancer incidence rates in
      Japan. Cox proportional hazard models were used to estimate hazard ratios (HR)
      and 95% confidence intervals (CI) according to the exposure of interest. The
      median age at epithelial ovarian cancer diagnosis was 59 years, with a median
      follow-up before diagnosis of 7.6 years. There were no statistically significant
      associations for age at menarche or first birth, breastfeeding, use of exogenous
      hormones, menopausal status at cohort enrollment, height, body mass index,
      smoking status, second-hand smoke, alcohol consumption, physical activity and
      family history of cancer in a first-degree relative. The linear decrease in HR
      associated with each additional birth was 0.75 (95% CI 0.56-0.99). Among women
      who usually slept >7 h per day, an HR of 0.4 (95% CI 0.2-0.9) emerged compared to
      those who slept <6 h. This study did not confirm risk factors for epithelial
      ovarian cancer among Japanese women that have been reported in studies carried
      out elsewhere. Usual sleep duration of >7 h per day was inversely associated with
      epithelial ovarian cancer risk, which is a novel finding that needs to be
      confirmed in other studies.

PMID- 21904775
TI  - Novel anti-cancer role of naphthazarin in human gastric cancer cells.
AB  - Gastric cancer is one of the most common malignant tumors and the second cause of
      cancer-related deaths worldwide. Naphthoquinones such as juglone and plumbagin
      are compounds used extensively to overcome resistance to chemotherapeutic agents
      in cancers due to their cytotoxic role. This study is the first to investigate
      the anti-cancer effect of naphthazarin (Naph), one of the naphthaquinones, in
      human gastric cancer AGS cells. We showed that Naph exhibited effective
      preferential cell growth inhibition via G2/M phase arrest and apoptosis, which
      was associated with reduced levels of Cdc2 and Cdc25C expression. Naph also
      increased cleaved caspase-3 and Poly ADR(adenosine diphosphate ribose) Polymerase
      expression, gamma-H2AX expression (an indicator of DNA double strand breaks) and
      DNA fragmentation. We also found the generation of reactive oxygen species is a
      critical mediator in Naph-induced cell growth inhibition and apoptosis. The non
      protein antioxidant, glutathione significantly abolished Naph-mediated inhibition
      of cell growth and apoptosis. Taken together, our findings showed that Naph not
      only inhibited cell growth, but also induced apoptosis of AGS cells, suggesting
      that Naph may be a potential candidate for cancer therapy against gastric
      cancers.

PMID- 21904776
TI  - A new membrane re-anchored protein originating from GPC3 against hepatoma cells
      HepG2.
AB  - The aim of this study was to confirm the localization of recombinant pGPC3+afp
      EGFP which expressed a new re-anchored protein named GPC3+afp-EGFP on the
      cytoplasmic membrane and to investigate its functions against hepatocellular
      carcinoma (HCC). EGFP expression in transfected HepG2 cells was observed using
      fluorescence and a confocal microscope. pGPC3+afp-EGFP expression was detected in
      membranous and soluble proteins extracted from transfected human embryonic kidney
      293 cells by Western blot analysis using GPC3 mAb. The proliferation of
      transfected HepG2 cells with pGPC3+afp-EGFP (experimental group) was detected
      using SRB assay and compared to those of transfected HepG2 cells with pGPC3
      (control group) and non-transfected HepG2 cells (blank group). Quantitative
      analysis of mRNA expression of the Fas gene was conducted by real-time PCR using
      the beta-actin housekeeping gene as the internal control at variable times.
      Apoptotic HepG2 cells in the three groups were counted and statistically analyzed
      by a contingency table Chi-square test using Spss 11.5 software and TUNEL assay.
      Production of both TNF-alpha and IFN-gamma/IL2 was detected by ELISPOT after co
      cultivation of transfected HepG2 cells with peripheral blood lymphocytes at
      different time-points in the experimental group. Green fluorescence was mainly
      found around the transfected HepG2 cell periphery through fluorescence and
      confocal microscopy. GPC3+afp-EGFP could not be detected in soluble protein but
      only in membranous protein. Proliferation curves showed that the proliferative
      quantities of transfected HepG2 cells in the experimental group decreased,
      whereas the mRNA expression of the Fas gene increased significantly compared to
      those of the other two groups. The numbers of apoptotic cells in the experimental
      group were significantly higher compared to those in the other two groups, as
      shown by statistical analysis. Both TNF-alpha and IFN-gamma/IL2 were induced and
      were much higher in the experimental groups than in the diverse control groups at
      variable times. A new re-anchored protein GPC3+afp-EGFP expressed by recombinant
      pGPC3+afp-EGFP was localized on the cytoplasmic membrane, and had multiple
      functions against HCC, such as inhibition of transfected HepG2 cell
      proliferation, promotion of transfected HepG2 apoptosis and induction of
      antitumor cytokine excretion.

PMID- 21904777
TI  - Synergistic antitumor effect of beta-elemene and etoposide is mediated via
      induction of cell apoptosis and cell cycle arrest in non-small cell lung
      carcinoma cells.
AB  - beta-Elemene, an anticancer agent, was isolated from the traditional Chinese
      medicine plant, curcuma aromatica. In this study, we investigated the synergistic
      antitumor effect of beta-elemene and etoposide phosphate (VP-16) in A549 non
      small cell lung carcinoma cells. The cells were treated with beta-elemene (20 or
      50 ug/ml), VP-16 (15 ug/ml) or the combination of both for 24 h. Compared to the
      treatment with beta-elemene or VP-16 alone, an increased antitumor activity was
      observed with the combination of both, which was mediated by the cleavage of
      PARP, the up-regulation of Bax, p53 and p21, and the suppression of cyclin D1.
      These results suggest that the combination of beta-elemene and VP-16 may be a
      promising therapeutic option for lung cancer.

PMID- 21904778
TI  - Dosing of glucocorticosteroids in nephrotic syndrome.

PMID- 21904780
TI  - Can sugammadex encapsulation eliminate the antigenic activity of aminosteroidal
      neuromuscular blocking agent?

PMID- 21904779
TI  - Pentazocine increases bispectral index without surgical stimulation during
      nitrous oxide-sevoflurane anesthesia.
AB  - Although there have been a large number of reports on the effects of opioids on
      the bispectral index (BIS) during anesthesia, the effects of pentazocine on the
      BIS have not been reported. In this study, 60 patients scheduled for elective
      oral surgery [30 females, 30 males; all American Society of Anesthesiologists
      Physical Status (ASA PS) category 1] were enrolled in the trials. Maintaining
      gender parity, we randomly assigned the patients to one of three groups:
      pentazocine group (0.3 mg/kg; n = 20), fentanyl group (1 MUg/kg; n = 20), or
      saline group (n = 20); these opioids were administered intravenously 15 min after
      the intubation. Anesthesia was induced with thiopental and vecuronium bromide and
      maintained with nitrous oxide (4 l/min)-oxygen (2 l/min)-sevoflurane (1%). At 15
      min after the intubation, mean arterial blood pressure (MAP), heart rate (HR),
      and BIS index were recorded as baseline values. MAP, HR, and BIS values were
      measured at 2.5-min after the intubation up to 30 min. All data were expressed as
      the mean +/- standard deviation. Differences in BIS values, MAP, and HR among the
      three groups throughout the experiment were analyzed using two-way repeated
      measures analysis of variance (ANOVA), and demographic data among the three
      groups were analyzed using one-way ANOVA. Post hoc comparisons were performed
      using Fisher's protected least significant difference test. A P value of <0.05
      was considered to indicate statistically significance. MAP and HR showed no
      significant differences among the three groups during the study. BIS values
      significantly increased between 5 and 15 min after the intubation relative to the
      baseline value in the pentazocine group (P < 0.001), and BIS values in this group
      were significantly during this time period than those in the fentanyl and saline
      group (P < 0.001). BIS values were not significantly different between the
      fentanyl group and saline group. These results indicated that pentazocine, but
      not fentanyl, under nitrous oxide-sevoflurane anesthesia caused a statistically
      significant increase in BIS in our patients.

PMID- 21904781
TI  - Impact of remifentanil introduction on practice patterns in general anesthesia.
AB  - PURPOSE: The introduction of new medicine can change clinical practice patterns
      and may affect patient outcomes. In the present study, we investigated whether
      introduction of remifentanil in Japan affected the practice patterns of
      anesthesia. METHODS: Using the Japanese Diagnosis Procedure Combination database,
      we extracted records of 423,491 patients who underwent surgery with general
      anesthesia in 243 hospitals before (2006) and after (2007) the introduction of
      remifentanil, and identified anesthetic agents used for each patient. A
      hierarchical mixed-effects logistic regression analysis was performed to analyze
      the factors that affected selection of remifentanil. Further, we compared
      postoperative length of stay (LOS), in-hospital mortality, and total costs
      between 2006 and 2007. RESULTS: In 2007, remifentanil was used for up to 41.4% of
      all general anesthesia, accompanied by a reduction in nitrous oxide use and an
      increase in total intravenous anesthesia. Female gender, increasing age, and
      preoperative comorbidities including diabetes mellitus, hypertension, liver
      cirrhosis, and chronic renal failure were positively associated with the use of
      remifentanil, whereas accompanying cardiac disease and co-application of epidural
      anesthesia were negatively associated. In 2007, a similar in-hospital death rate,
      similar or decreased total costs, slightly reduced duration of anesthesia, and
      substantially reduced postoperative LOS were seen compared to those in 2006.
      CONCLUSIONS: Our data revealed rapid changes in practice patterns in anesthesia
      after the introduction of remifentanil in Japan. Remifentanil was used more often
      in patients with comorbidities and without epidural anesthesia, and its
      introduction did not affect increase in total medical costs.

PMID- 21904782
TI  - A case of cardiopulmonary arrest caused by laxatives-induced hypermagnesemia in a
      patient with anorexia nervosa and chronic renal failure.
AB  - We report a case of laxatives induced severe hypermagnesemia complicated with
      cardiopulmonary arrest. A 55-year-old woman, with nephritic syndrome and anorexia
      nervosa, was later transported to our emergency room (ER) because of oliguria and
      consciousness disturbance. During transfer to the intensive care unit from the
      ER, cardiopulmonary arrest suddenly occurred. Cardiopulmonary resuscitation was
      immediately performed, and spontaneous circulation was restored after 3 min.
      Thereafter, administration of dopamine, norepinephrine, and epinephrine was
      required to maintain systolic blood pressure at 80 mmHg. Arterial blood gas
      analysis showed severe metabolic alkalosis, and blood biochemical tests revealed
      hypermagnesemia (serum magnesium concentration, 18.5 mg/dl) and renal
      dysfunction. Continuous infusion of diuretics followed by massive hydration and
      continuous hemodiafiltration (CHDF) was started. Five days after starting CHDF,
      magnesium concentration was almost normalized and administration of catecholamine
      was stopped. It was thought that progression of renal dysfunction that occurred
      in the patient taking a magnesium product for chronic constipation caused
      reduction in magnesium excretion ability, resulting in hypermagnesemia-induced
      cardiopulmonary arrest. To avoid a rebound phenomenon following magnesium flux
      from cells, continuous blood purification seems to be an effective treatment for
      symptomatic hypermagnesemia.

PMID- 21904783
TI  - Difference of fibromyalgia symptom scale between the Japanese version of the 2010
      ACR preliminary diagnostic criteria for fibromyalgia and the modification of the
      ACR preliminary diagnostic criteria for fibromyalgia.

PMID- 21904784
TI  - Celecoxib, a cyclooxygenase-2 inhibitor, improved upper gastrointestinal lesions
      in rheumatoid arthritis patients as assessed by endoscopic evaluation.
AB  - We prospectively evaluated the effects of celecoxib (CEL) on the gastrointestinal
      (GI) tract of rheumatoid arthritis (RA) patients with endoscopically identified
      GI mucosal injury after therapeutic switching from the long-term use of
      traditional nonsteroidal anti-inflammatory drugs (NSAIDs). Upper GI endoscopy was
      performed on RA patients who had been treated with NSAIDs for >=3 months. GI
      mucosal injury was evaluated according to the modified LANZA score. Patients with
      mucosal injury without ulcers were switched from NSAIDs to CEL, while those with
      ulcers were switched to CEL with famotidine after ulcer healing. At week 16 of
      treatment, GI mucosal injury was endoscopically revaluated. An efficacy analysis
      was performed before therapeutic switching and at 8 and 16 weeks post-switching.
      Endoscopic analysis revealed GI mucosal injury, including six ulcers, in 45 of
      the 82 patients (54.9%). Sixteen weeks after switching to CEL, LANZA scores were
      significantly improved [2.1 +/- 0.8 (pre-switching) vs. 1.6 +/- 1.3, P = 0.0073]
      in patients with LANZA scores of 1, 2, or 3 (n = 35). The Disease Activity Score
      using 28 joint counts (DAS28) [erythrocyte sedimentation rate item score (ESR4)
      (P = 0.0257) and C-reactive protein item score (CRP4) (P = 0.0031)] was also
      significantly improved by week 16. Based on these results, we conclude that
      preexisting NSAID-induced upper GI injury is improved following therapeutic
      switching to CEL without any reduction in analgesic efficacy.

PMID- 21904785
TI  - Diffuse alveolar damage in patients with dermatomyositis: a six-case series.
AB  - The clinical course of diffuse alveolar damage (DAD) was studied in six
      consecutive cases of dermatomyositis (DM) based on our hospital records over 8
      years. Three patients had severe myopathy at presentation, and the other three
      patients showed clinically amyopathic DM (CADM). Interstitial pneumonia in all
      patients developed shortly after they manifested DM. DAD in five deceased
      patients, which was proven pathologically, did not respond to steroid therapy
      combined with cyclosporine or tacrolimus. Of these, two patients began receiving
      combination therapy before suffering respiratory symptoms, and one of them had
      elevated serum Krebs von der Lungen-6 (KL-6) levels before visible abnormalities
      appeared on a plain chest X-ray. Only one patient with CADM survived; this
      patient received intravenously administered pulse cyclophosphamide (IVCY) therapy
      intravenously for DAD from the early stage. Delayed adjunctive IVCY was
      ineffective for progressed DAD in the remaining five patients. Elevated serum
      ferritin levels were observed in all four patients examined and might have
      predicted the lethal DAD, as in a previous report. In conclusion, promptly
      beginning IVCY therapy may be beneficial for patients with DM and interstitial
      pneumonia who show elevated serum levels of ferritin or KL-6 with minimal
      pulmonary abnormalities.

PMID- 21904786
TI  - Neurotrophins: potential therapeutic tools for the treatment of spinal cord
      injury.
AB  - Spinal cord injury permanently disrupts neuroanatomical circuitry and can result
      in severe functional deficits. These functional deficits, however, are not
      immutable and spontaneous recovery occurs in some patients. It is highly likely
      that this recovery is dependent upon spared tissue and the endogenous plasticity
      of the central nervous system. Neurotrophic factors are mediators of neuronal
      plasticity throughout development and into adulthood, affecting proliferation of
      neuronal precursors, neuronal survival, axonal growth, dendritic arborization and
      synapse formation. Neurotrophic factors are therefore excellent candidates for
      enhancing axonal plasticity and regeneration after spinal cord injury.
      Understanding growth factor effects on axonal growth and utilizing them to alter
      the intrinsic limitations on regenerative growth will provide potent tools for
      the development of translational therapeutic interventions for spinal cord
      injury.

PMID- 21904788
TI  - Combining cell-based therapies and neural prostheses to promote neural survival.
AB  - Cochlear implants provide partial restoration of hearing for profoundly deaf
      patients by electrically stimulating spiral ganglion neurons (SGNs); however,
      these neurons gradually degenerate following the onset of deafness. Although the
      exogenous application of neurotrophins (NTs) can prevent SGN loss, current
      techniques to administer NTs for long periods of time have limited clinical
      applicability. We have used encapsulated choroid plexus cells (NTCells; Living
      Cell Technologies, Auckland, New Zealand) to provide NTs in a clinically viable
      manner that can be combined with a cochlear implant. Neonatal cats were deafened
      and unilaterally implanted with NTCells and a cochlear implant. Animals received
      chronic electrical stimulation (ES) alone, NTs alone, or combined NTs and ES (ES
      + NT) for a period of as much as 8 months. The opposite ear served as a deafened
      unimplanted control. Chronic ES alone did not result in increased survival of
      SGNs or their peripheral processes. NT treatment alone resulted in greater SGN
      survival restricted to the upper basal cochlear region and an increased density
      of SGN peripheral processes. Importantly, chronic ES in combination with NTs
      provided significant SGN survival throughout a wider extent of the cochlea, in
      addition to an increased peripheral process density. Re-sprouting peripheral
      processes were observed in the scala media and scala tympani, raising the
      possibility of direct contact between peripheral processes and a cochlear implant
      electrode array. We conclude that cell-based therapy is clinically viable and
      effective in promoting SGN survival for extended durations of cochlear implant
      use. These findings have important implications for the safe delivery of
      therapeutic drugs to the cochlea.

PMID- 21904787
TI  - Cell therapy for multiple sclerosis.
AB  - The spontaneous recovery observed in the early stages of multiple sclerosis (MS)
      is substituted with a later progressive course and failure of endogenous
      processes of repair and remyelination. Although this is the basic rationale for
      cell therapy, it is not clear yet to what degree the MS brain is amenable for
      repair and whether cell therapy has an advantage in comparison to other
      strategies to enhance endogenous remyelination. Central to the promise of stem
      cell therapy is the therapeutic plasticity, by which neural precursors can
      replace damaged oligodendrocytes and myelin, and also effectively attenuate the
      autoimmune process in a local, nonsystemic manner to protect brain cells from
      further injury, as well as facilitate the intrinsic capacity of the brain for
      recovery. These fundamental immunomodulatory and neurotrophic properties are
      shared by stem cells of different sources. By using different routes of delivery,
      cells may target both affected white matter tracts and the perivascular niche
      where the trafficking of immune cells occur. It is unclear yet whether the
      therapeutic properties of transplanted cells are maintained with the duration of
      time. The application of neural stem cell therapy (derived from fetal brain or
      from human embryonic stem cells) will be realized once their purification, mass
      generation, and safety are guaranteed. However, previous clinical experience with
      bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of
      autologous cells have opened the way to their experimental application in MS. An
      initial clinical trial has established the probable safety of their intravenous
      and intrathecal delivery. Short-term follow-up observed immunomodulatory effects
      and clinical benefit justifying further clinical trials.

PMID- 21904790
TI  - Neural stem cell transplantation as a therapeutic approach for treating lysosomal
      storage diseases.
AB  - Treating the central nervous system manifestations of subjects with neuropathic
      lysosomal storage diseases remains a major technical challenge. This is because
      of the low efficiency by which lysosomal enzymes in systemic circulation are able
      to traverse the blood brain barrier into the central nervous system. Intracranial
      transplantation of neural stems cells genetically modified to overexpress the
      respective deficient enzymes represents a potential approach to addressing this
      group of diseases. The unique properties of neural stem cells and progenitor
      cells, such as their ability to migrate to distal sites, differentiate into
      various cell types and integrate within the host brain without disrupting normal
      function, making them particularly attractive therapeutic agents. In addition,
      neural stem cells are amenable to ex vivo propagation and modification by gene
      transfer vectors. In this regard, transplanted cells can serve not only as a
      source of lysosomal enzymes but also as a means to potentially repair the injured
      brain by replenishing the organ with healthy cells and effecting the release of
      neuroprotective factors. This review discusses some of the well-characterized
      neural stem cell types and their possible use in treating neuropathic lysosomal
      storage diseases such as the Niemann Pick A disease.

PMID- 21904789
TI  - Stem cell transplantation for motor neuron disease: current approaches and future
      perspectives.
AB  - Motor neuron degeneration leading to muscle atrophy and death is a pathological
      hallmark of disorders, such as amyotrophic lateral sclerosis or spinal muscular
      atrophy. No effective treatment is available for these devastating diseases. At
      present, cell-based therapies targeting motor neuron replacement, support, or as
      a vehicle for the delivery of neuroprotective molecules are being investigated.
      Although many challenges and questions remain, the beneficial effects observed
      following transplantation therapy in animal models of motor neuron disease has
      sparked hope and a number of clinical trials. Here, we provide a comprehensive
      review of cell-based therapeutics for motor neuron disorders, with a particular
      emphasis on amyotrophic lateral sclerosis.

PMID- 21904792
TI  - Immune mechanisms underlying the beneficial effects of autologous hematopoietic
      stem cell transplantation in multiple sclerosis.
AB  - A recent phase I/II clinical trial drew serious attention to the therapeutic
      potential of autologous hematopoietic stem cell transplantation (AHSCT) in
      multiple sclerosis. However, questions were raised as to whether these beneficial
      effects should be attributed to the newly reconstituted immune system per se, or
      to the lymphoablative conditioning regimen-induced immunosuppression, given that
      T-cell depleting combinational drug therapies were used in the study. We discuss
      here the possibility that both AHSCT and T-cell depleting therapies may re
      program alternatively the immune system, and why transplantation of CD34+
      hematopoietic stem cells may offer AHSCT a possible advantage regarding long-term
      remission.

PMID- 21904793
TI  - Modulation of intramolecular charge transfer emission inside micelles: a
      fluorescence probe for studying microenvironment of micellar assemblies.
AB  - Modulation of intramolecular charge transfer reaction of ethyl ester of N,N
      dimethylaminonaphthyl-(acrylic)-acid (EDMANA) in anionic sodium dodecyl sulfate
      (SDS), cationic cetyltrimethylammonium bromide (CTAB) and non-ionic p-tert
      octylphenoxy polyoxyethanol (Triton-X 100, TX-100) micelles has been addressed
      using steady state and time resolved spectroscopy. The interaction of the CT
      probe EDMANA with micelles and its location inside the micelles have been
      investigated by the study of fluorescence spectral band position of EDMANA in
      micelle, the effective polarity of micelle-water interface and cetyl pyridinium
      chloride induced fluorescence quenching measurement. The effects of urea on the
      properties of the micelles such as Critical Micelle Concentration and the
      interaction between EDMANA and micelles have been explored using EDMANA as
      emission probe.

PMID- 21904794
TI  - A novel approach for determination of free fatty acids in vegetable oils by a
      flow injection system with manual injection.
AB  - A non-aqueous flow injection method for determining free fatty acid (FFA) content
      in corn and sunflower oil samples was developed. A single-line manifold system
      was built by modification of an HPLC for flow injection analysis (FIA). Without
      pre-treatment, oil samples were injected into a n-propanol solution containing
      KOH and phenolphthalein (PHP). The main parameters, such as flow rate of carrier
      phase, length, geometry, inner diameters of the coils and reagent concentration
      were all optimized. The proposed FIA method was validated for precision,
      accuracy, linear region, limit of detection (LOD) and limit of quantification
      (LOQ). The intra- and inter-day measurements of the precision of the method were
      found to be within the limits of acceptance criteria (RSD < 1%), and were rugged
      when the method was performed by a different analyst. The linear concentration
      range was calculated as 0.09-1.50 and 0.07-1.40 FFA% for corn and sunflower oils,
      correspondingly. The LOD and LOQ were found to be 7.53 * 10(-4)-2.28 * 10(-3)
      oleic acid % and 7.11 * 10(-4)-2.23 * 10(-3) oleic acid % for corn and sunflower
      oils, respectively. The results were compared with those obtained by the AOCS (Ca
      5a-40) method using statistical t and F tests, and a significant difference was
      not observed between the methods at a 95% confidence level. The proposed method
      is suitable for quality control of routine applications due to its simplicity,
      high sample throughput, and economy of solvents and sample, offering considerable
      promise as a low cost analytical system that needs minimum human intervention
      over long periods of time.

PMID- 21904791
TI  - Myelin regeneration in multiple sclerosis: targeting endogenous stem cells.
AB  - Regeneration of myelin sheaths (remyelination) after central nervous system
      demyelination is important to restore saltatory conduction and to prevent axonal
      loss. In multiple sclerosis, the insufficiency of remyelination leads to the
      irreversible degeneration of axons and correlated clinical decline. Therefore, a
      regenerative strategy to encourage remyelination may protect axons and improve
      symptoms in multiple sclerosis. We highlight recent studies on factors that
      influence endogenous remyelination and potential promising pharmacological
      targets that may be considered for enhancing central nervous system
      remyelination.

PMID- 21904795
TI  - Electrospray ionization tandem mass spectrometry of sodiated adducts of
      cholesteryl esters.
AB  - Cholesteryl esters (CE) are important lipid storage molecules. The present study
      demonstrates that sodiated adducts of CE molecular species form positive ions
      that can be detected in both survey scan mode as well as by exploiting class
      specific fragmentation in MS/MS scan modes. A common neutral loss for CE is the
      loss of cholestane (NL 368.5), which can be used to specifically quantify tissue
      CE molecular species. Using this MS/MS technique, CE molecular species were
      quantified in mouse monocyte-derived macrophages (J774 cells) incubated with
      either linoleic (18:2) or arachidonic acid (20:4). These studies revealed that
      arachidonic acid was not only incorporated into the CE pool, but also was
      elongated resulting in the accumulation of 22:4 and 24:4 CE molecular species in
      macrophages. Additionally, this technique was used to quantify CE molecular
      species present in crude lipid extracts from plasma of female mice fed a Western
      diet, which led to an enrichment in CE molecular species containing
      monounsaturated fatty acids compared to female mice fed a normal chow diet. Last,
      NL 368.5 spectra revealed the oxidation of the aliphatic fatty acid residues of
      CE molecular species containing polyunsaturated fatty acids. Taken together,
      these studies demonstrate the utility of using sodiated adducts of CE in
      conjunction with direct infusion electrospray ionization tandem mass spectrometry
      to rapidly quantify CE molecular species in biological samples.

PMID- 21904797
TI  - Impedance spectroscopy in monitoring the maturation of stem cell-derived retinal
      pigment epithelium.
AB  - The development and differentiation of stem cell-derived impermeable retinal
      pigment epithelium (RPE) with tight junctions (TJs) is a gradual process that is,
      at confluence, controlled by cell-to-cell contact. The objective of this study
      was to evaluate the use of electric impedance spectroscopy (EIS) to follow the
      maturation and development of barrier function in human embryonic stem cell
      derived RPE (hESC-RPE). Barrier function was assessed using EIS, permeability
      measurements, and microscopic inspection in intact cells and following calcium
      sequestration with ethylene glycol tetraacetic acid (EGTA). The results showed
      that the cultures with the most mature morphology had the highest impedance and
      the lowest permeability values. The EIS of samples of high integrity fitted well
      to the equivalent model of a single RC circuit, whereas the semicircular shape of
      the Nyquist plots was distorted for samples of lower integrity. EGTA treatment
      resulted in lower impedance values and changes in the shapes of plots. Our
      results show that EIS-as a measure of overall maturity and integrity of the
      epithelium-is useful when evaluating the maturity of cell cultures. It is highly
      warranted in future transplantation therapies and in in vitro cell culture models
      in drug development.

PMID- 21904796
TI  - Low-molecular-weight lignin-rich fraction in the extract of cultured Lentinula
      edodes mycelia attenuates carbon tetrachloride-induced toxicity in primary
      cultures of rat hepatocytes.
AB  - The extract of cultured Lentinula edodes mycelia (LEM) is a medicinal food
      ingredient that has hepatoprotective effects. In this study, we fractionated the
      LEM extract to explore novel active compounds related to hepatoprotection by
      using primary cultures of rat hepatocytes exposed to carbon tetrachloride
      (CCl(4)). The LEM extract and the fractions markedly inhibited the release of
      alanine aminotransferase (ALT) from hepatocytes damaged by CCl(4) into the
      culture medium. The strongest hepatocyte-protective activity was seen in a
      fraction (Fr. 2) in which a 50% ethanol extract was further eluted with 50%
      methanol and separated using reverse-phase HPLC. Fr. 2 had an average molecular
      weight of 2753, and the main components are lignin (49%) and saccharides (36%, of
      which xylose comprises 41%). Therefore, Fr. 2 was presumed to be a low-molecular
      weight compound consisting mainly of lignin and xylan-like polysaccharides. The
      hepatocyte-protective activity was observed even after digestion of xylan-like
      polysaccharides in Fr.2 and confirmed with low-molecular-weight lignin (LM
      lignin) alone. In addition, Fr. 2, the xylan-digested Fr. 2 and LM-lignin showed
      higher superoxide dismutase (SOD)-like activity than the LEM extract. These
      results suggested that the effective fraction in the LEM extract related to
      hepatocyte protection consisted mainly of LM-lignin, and its antioxidant activity
      partially contributes to the hepatocyte-protective activity of the LEM extract.

PMID- 21904798
TI  - Direct laser photo-induced fluorescence determination of bisphenol A.
AB  - Classical photo-induced fluorescence methods are conducted in two steps: a UV
      irradiation step in order to form a photo-induced compound followed by its
      fluorimetric determination. Automated flow injection methods are frequently used
      for these analyses. In this work, we propose a new method of direct laser photo
      induced fluorescence analysis. This new method is based on direct irradiation of
      the analyte in a fluorimetric cell in order to form a photo-induced fluorescent
      compound and its direct fluorimetric detection during a short irradiation time.
      Irradiation is performed with a tuneable Nd:YAG laser to select the optimal
      excitation wavelength and to improve the specificity. It has been applied to the
      determination of bisphenol A, an endocrine disrupter compound that may be a
      potential contaminant for food. Irradiation of bisphenol A at 230 nm produces a
      photo-induced compound with a much higher fluorescence quantum yield and specific
      excitation/emission wavelengths. In tap water, the fluorescence of bisphenol A
      increases linearly versus its concentration and, its determination by direct
      laser photo-induced fluorescence permits to obtain a low limit of detection of 17
      MUg L(-1).

PMID- 21904799
TI  - Feasibility of using atmospheric pressure matrix-assisted laser
      desorption/ionization with ion trap mass spectrometry in the analysis of
      acetylated xylooligosaccharides derived from hardwoods and Arabidopsis thaliana.
AB  - The atmospheric pressure matrix-assisted laser desorption/ionization with ion
      trap mass spectrometry (AP-MALDI-ITMS) was investigated for its ability to
      analyse plant-derived oligosaccharides. The AP-MALDI-ITMS was able to detect
      xylooligosaccharides (XOS) with chain length of up to ten xylopyranosyl residues.
      Though the conventional MALDI-time-of-flight/mass spectrometry (TOF/MS) showed
      better sensitivity at higher mass range (>m/z 2,000), the AP-MALDI-ITMS seems to
      be more suitable for detection of acetylated XOS, and the measurement also
      corresponded better than the MALDI-TOF/MS analysis to the actual compositions of
      the pentose- and hexose-derived oligosaccharides in a complex sample. The
      structures of two isomeric aldotetrauronic acids and a mixture of acidic XOS were
      elucidated by AP-MALDI-ITMS using multi-stages mass fragmentation up to MS(3).
      Thus, the AP-MALDI-ITMS demonstrated an advantage in determining both mass and
      structures of plant-derived oligosaccharides. In addition, the method of
      combining the direct endo-1,4-beta-D-xylanase hydrolysis of plant material, and
      then followed by AP-MALDI-ITMS detection, was shown to recognize the substitution
      variations of glucuronoxylans in hardwood species and in Arabidopsis thaliana. To
      our knowledge, this is the first report to demonstrate the acetylation of
      glucuronoxylan in A. thaliana. The method, which requires only a small amount of
      plant material, such as 1 to 5 mg for the A. thaliana stem material, can be
      applied as a high throughput fingerprinting tool for the fast comparison of
      glucuronoxylan structures among plant species or transformants that result from
      in vivo cell wall modification.

PMID- 21904800
TI  - Characterization of "oil on copper" paintings by energy dispersive X-ray
      fluorescence spectrometry.
AB  - Energy dispersive X-ray fluorescence is a common analytical tool for layer
      thickness measurements in quality control processes in the coating industry, but
      there are scarce microanalytical applications in order to ascertain semi
      quantitative or quantitative information of painted layers. "Oil on copper"
      painting becomes a suitable material to be analysed by means of X-ray
      fluorescence spectrometry, due to the metallic nature of substrate and the
      possibility of applying layered models as used in coating industry. The aim of
      this work is to study the suitability of a quantitative energy dispersive X-ray
      fluorescence methodology for the assessment of the areal distribution of pigments
      and the characterization of painting methods on such kind of pictorial artworks.
      The method was calibrated using standard reference materials: dried droplets of
      monoelemental standard solutions laid on a metallic plate of copper. As an
      example of application, we estimated pigment mass distribution of two "oil on
      copper" paintings from the sixteenth and eighteenth centuries. Pictorial layers
      have been complementarily analysed by X-ray diffraction. Apart of the supporting
      media made of copper or brass, we could identify two different superimposed
      layers: (a) a preparation layer mainly composed by white lead and (b) the
      pictorial layer of variable composition depending on the pigments used by the
      artist on small areas of the painting surface. The areal mass distribution of the
      different elements identified in the painting pigments (Ca, Cr, Mn, Fe, Zn, Cd,
      Hg and Pb) have been determined by elemental mapping of some parts of the
      artworks.

PMID- 21904801
TI  - Amorphous carbon nanoparticles: a versatile label for rapid diagnostic
      (immuno)assays.
AB  - Carbon nanoparticles (CNPs) labeled with reporter molecules can serve as
      signaling labels in rapid diagnostic assays as an alternative to gold, colored
      latex, silica, quantum dots, or up-converting phosphor nanoparticles. Detailed
      here is the preparation of biomolecule-labeled CNPs and examples of their use as
      a versatile label. CNPs can be loaded with a range of biomolecules, such as DNA,
      antibodies, and proteins (e.g., neutravidin or a fusion protein of neutravidin
      with an enzyme), and the resulting conjugates can be used to detect analytes of
      high or low molecular mass.

PMID- 21904803
TI  - Huffing-induced cardiomyopathy: a case report.
AB  - The intentional inhalation of fumes from gasoline or solvents for recreational
      purposes is commonly known as Huffing, Sniffing or Dusting (Anderson and Loomis
      in Am Fam Physician 68(5):869-874, 2003). Inhalant abuse is known to be "Cardio
      toxic", causing sudden death and chronic myocardial damage (Meadows and Verghese
      in South Med J 89(5):455-462, 1996; Anderson and Loomis in Am Fam Physician
      68(5):869-874, 2003). We report a 20-year-old white man who presented with
      altered mental status following ingestion of multiple alprazolam and oxycodone
      tablets. He was found to have diffused ST-T changes on his EKG. Cardiac enzymes
      were found to be elevated-CK: 599 U/L, CK-MB: 16.8 ng/mL and Troponin: 0.78
      ng/mL. A transthoracic echocardiogram (TTE) revealed global left ventricular (LV)
      dysfunction with an ejection fraction (EF) of 10-15%. During hospitalization, the
      cardiac enzymes started trending downward and this was followed by spontaneous
      resolution of the LV dysfunction. The patient also admitted to inhaling "Dust
      Off" spray 2-3 days prior to admission. Inhalant abuse can cause cardiomyopathy
      and should be considered a probable cause in patients presenting with cardiac
      dysfunction of unknown etiology, particularly in teenagers and young adults.

PMID- 21904802
TI  - Evaluation of the potential of PET-MRI fusion for detection of liver metastases
      in patients with neuroendocrine tumours.
AB  - OBJECTIVES: This study was performed to assess the role of retrospective PET-MRI
      fusion with Ga-68-DOTA(0)-Phe(1)-Tyr(3)-octreotide (Ga-68-DOTATOC) PET and Gd-EOB
      DTPA MRI in the detection of hepatic metastases from neuroendocrine tumours
      (NET). METHODS: Twenty-two consecutive patients with suspected liver metastases
      from histopathologically proven NET were examined with Gd-EOB-DTPA MRI and
      multiphase contrast-enhanced Ga-68-DOTATOC PET/CT. PET and MRI images were
      retrospectively fused using commercially available software. Two physicians
      experienced in nuclear medicine and radiology analysed the images to assess
      diagnostic confidence and characterise liver lesions. RESULTS: A total of 181
      lesions were detected. PET-MRI showed a sensitivity of 91.2% (significantly
      superior to PET/CT; P < 0.05) and a specificity of 95.6% (significantly superior
      to MRI; P < 0.05). PET/CT had a sensitivity of 73.5% and a specificity of 88.2%.
      MRI had a sensitivity of 87.6% and a specificity of 86.8%. The area under the
      curve was 0.98 for PET-MRI, 0.96 for MRI, and 0.89 for PET/CT (P < 0.05).
      CONCLUSIONS: Retrospectively fused PET-MRI was superior to multiphase contrast
      enhanced Ga-68-DOTATOC PET/CT and Gd-EOB-DTPA MRI in the detection of NET liver
      metastases. It was more sensitive than PET/CT and more specific than MRI. Fused
      PET-MRI therefore seems well suited for surgical and interventional treatment
      planning of NET liver metastases. KEY POINTS: * Ga-68-DOTATOC PET-Gd-EOB-DTPA MRI
      fusion can improve imaging of liver metastases of neuroendocrine tumours. * This
      technique appears more sensitive than PET/CT for staging NET hepatic metastases.
      * Ga-68-DOTATOC PET-Gd-EOB-DTPA MRI fusion is more specific than MRI alone.

PMID- 21904804
TI  - A dentist's role: prevention of snoring at temporary refuges for victims of the
      East Japan earthquake and the Fukushima Daiichi Nuclear Power Plant accident on
      March 11, 2011.

PMID- 21904805
TI  - Obstructive sleep apnea in epilepsy: a preliminary Egyptian study.
AB  - PURPOSE: The extent and clinical relevance of the association between epilepsy
      and sleep apnea are not previously studied in Egypt. What we wanted to know was
      the frequency of sleep apnea in Egyptian children with epilepsy and its influence
      on seizure frequency, other seizure characteristics, sleep complaint, and
      architecture. METHODS: All patients with epilepsy, aged up to 18 years, who
      underwent polysomnography were studied. Patients with any neurological disease
      apart from epilepsy, with psychiatric illness, had hypnotics, or sedatives or
      those with liver or kidney failure were excluded from the study. The patients
      were divided into two subgroups according to apnea/hypopnea index: group (1)
      patients without obstructive sleep apnea (OSA) and group (2) patients with OSA.
      For control group, we choose 12 healthy individuals, with age and sex matched to
      that of our patients. We studied the clinical characteristics of epilepsy, sleep
      history, and polysomnographic recording of the patients with epilepsy and the
      control. EEG digital and video monitoring was done for all patients. RESULTS:
      Eleven patients (42.3%) were found to have obstructive sleep apnea. Seizure
      frequency was significantly higher in the patients with OSA. Apart from apnea and
      hypopnea indices, all other sleep parameters did not differ between patients'
      subgroups. Hypopnea index in REM positively correlates with number of awaking.
      Apnea index in REM positively correlates with latency to deep sleep and to
      periodic leg movement. CONCLUSIONS AND RECOMMENDATIONS: Sleep apnea is frequent
      in patients with epilepsy. OSA may contribute to increase seizure frequency. We
      recommend investigating sleep apnea in all patients with epilepsy.

PMID- 21904807
TI  - Special issue, Phenology 2010 conference, Dublin, Ireland.

PMID- 21904806
TI  - Neurocognitive performance in children and adolescents with bipolar disorder: a
      review.
AB  - A number of studies have reported the evidence of cognitive deficits in adult
      bipolar patients. Recently, there has been a shift in research on neurocognitive
      performance in bipolar disorder (BD) towards examining younger age groups. A
      review of the literature on neurocognitive impairments in BD in childhood and
      adolescence was conducted. We searched systematically for studies in samples of
      age groups younger than 18 years of age in average that included either a healthy
      control group or normative data for the cognitive tests used. Twenty-one original
      articles were found and reviewed. Children and adolescents with BD show deficits
      in a variety of cognitive areas. The most consistent results were found for
      impairments in verbal memory. A majority of studies also indicated impairments in
      working memory. Similar pattern of neurocognitive impairment was found in
      children and adolescents as compared to adults suffering from BD. The
      neurocognitive deficits need to be recognized and incorporated into individual
      treatment programs.

PMID- 21904808
TI  - Exploratory study on the influence of climatological parameters on Mycoplasma
      hyopneumoniae infection dynamics.
AB  - The objective of the present work was to elucidate the potential relationship
      between Mycoplasma hyopneumoniae infection and seroconversion dynamics and
      climatological conditions in four groups of pigs from the same farm born in
      different seasons of the year. Nasal swabs and blood samples were taken from 184
      pigs at 1, 3, 6, 9, 12, 15, 18, 22 and 25 (slaughter age) weeks of age. Outside
      climatologic parameters, including temperature ( degrees C), relative humidity
      (%), precipitation (l/m(2)) and wind speed (m/s) were recorded weekly from
      January 2003 to June 2004. Percentage of nPCR detection of M. hyopneumoniae in
      nasal swabs was associated significantly with the weekly precipitation rate [P =
      0.0018, OR = 1.31 (IC = 1.11-1.55)]; the higher the precipitation rate, the
      higher the probability of being M. hyopneumoniae nPCR-positive. On the other
      hand, the percentage of seropositive pigs had a significant association with mean
      weekly temperature rate [P = 0.0012, OR = 0.89 [IC = 0.84-0.95]); the lower the
      temperature, the higher the probability of being M. hyopneumoniae seropositive.
      Animals born in autumn (when higher precipitations rates were recorded), entering
      finishing units in winter (when lower temperatures were recorded), and reaching
      slaughter in spring, had the highest probability of being infected by M.
      hyopneumoniae and the highest probability of being M. hyopneumoniae seropositive.

PMID- 21904809
TI  - Bile culture and susceptibility testing of malignant biliary obstruction via
      PTBD.
AB  - PURPOSE: To assess the information obtained by bile culture and susceptibility
      testing for malignant biliary obstruction by a retrospective one-center study.
      METHODS: A total of 694 patients with malignant biliary obstruction received
      percutaneous transhepatic biliary drainage during the period July 2003 to
      September 2010, and subsequently, bile specimens were collected during the
      procedure. Among the 694 patients, 485 were men and 209 were women, ranging in
      age from 38 to 78 years (mean age 62 years). RESULTS: A total of 42.9% patients
      had a positive bile culture (298 of 694). Further, 57 species of microorganisms
      and 342 strains were identified; gram-positive bacteria accounted for 50.9% (174
      of 342) and gram-negative bacteria accounted for 41.5% (142 of 342) of these
      strains. No anaerobes were obtained by culture during this study. The most common
      microorganisms were Enterococcus faecalis (41 of 342, 11.9%), Escherichia coli
      (34 of 342, 9.9%), Klebsiella pneumoniae (28 of 342, 8.2%), Staphylococcus
      epidermidis (19 of 342, 5.5%), Enterococcus (18 of 342, 5.3%), and Enterobacter
      cloacae (16 of 342, 4.7%). The percentage of beta-lactamase-producing gram
      positive bacteria was 27.6% (48 of 174), and the percentage of gram-negative
      bacteria was 19.7% (28 of 142). The percentage of enzyme-producing Escherichia
      coli was 61.7% (21 of 34). CONCLUSION: The bile cultures in malignant biliary
      obstruction are different from those in the Tokyo Guidelines and other benign
      biliary obstruction researches, which indicates that a different antibacterial
      therapy should be applied. Thus, knowledge of the antimicrobial susceptibility
      data could aid in the better use of antibiotics for the empirical therapy of
      biliary infection combined with malignant biliary obstruction.

PMID- 21904810
TI  - Endovascular treatment of in-stent occlusion: new technique for recanalization of
      long superficial femoral artery occlusion (direct stent puncture technique).
AB  - In-stent reocclusion is a frequent complication of endovascular treatment and
      stenting, especially in the superficial femoral artery. Neointimal hyperplasia is
      the main cause of this problem, but in many cases, it occurs as a result of the
      presence of stent strut fractures. The two treatment options are endovascular and
      surgical intervention. The effectiveness of endovascular interventions in
      patients with critical limb ischemia has been well established, but in some
      cases, crossing the occluded stent is difficult. We describe a new technique to
      recanalize long in-stent superficial femoral artery occlusions characterized by
      direct stent puncture, followed by retrograde-antegrade recanalization after
      antegrade failures.

PMID- 21904811
TI  - A systematical comparison of DFT methods in reproducing the interaction energies
      of halide series with protein moieties.
AB  - A systematic theoretical investigation on the interaction energies of halogen
      ionic bridges formed between halide ions and the polar H atoms bonded to N of
      protein moieties has been carried out by employing a variety of density
      functional methods. In this procedure, full geometry optimizations are performed
      at the Moller-Plesset second-order perturbation (MP2) level of theory in
      conjunction with the Dunning's augmented correlation-consistent basis set, aug-cc
      pVDZ. Subsequently, two distinct basis sets, i.e. 6-311++G(df,pd) and aug-cc
      pVTZ, are employed in the following single-point calculations so as to check the
      stability of the results obtained at the different levels of DFT. The performance
      of DFT methods has been evaluated by comparing the results with those obtained
      from the rigorous MP2 theory. It is shown that the B98, B97-1, and M05 give the
      lowest root-mean-square error (RMSE) for predicting fluoride-binding energies,
      M05-2X, MPW1B95, and MPW1PW91 have the best performance in reproducing chloride
      binding energies, B97-1, PBEKCIS, and PBE1KCIS present the optimal result for
      bromide-binding energies, while B97-1, MPW1PW91, and TPSS perform most well on
      iodide-binding energies. The popular B3LYP functional seems to be quite modest
      for studying halide-protein moiety interactions. In addition, the PBE1KCIS
      functional provide accuracies close to the computationally expensive MP2 method
      for the calculation of interaction energies of all halide-binding systems.

PMID- 21904812
TI  - Molecular dynamics simulations on the aggregation behavior of indole type organic
      dye molecules in dye-sensitized solar cells.
AB  - In Ti0(2) nanostructured dye-sensitized solar cells indole based organic dyes
      D149, D205 exhibits greater power conversion efficiency. Such organic dye
      molecules are easily undergone for aggregation. Aggregation in dye molecules
      leads to reduce electron transfer process in dye-sensitized solar cells.
      Therefore, anti-aggregating agents such as chenodeoxycholic acid are commonly
      added to organic dye solution in DSSCs. Studying aggregation of such dye
      molecules in the absence of semiconductors gives a detailed influence of anti
      aggregating agents on dye molecules. Atomistic level of molecular dynamics (MD)
      simulations were performed on aggregation of indole type dye molecules D149, D205
      and D205-F with anti-aggregating agent chenodeoxy cholic acid using AMBER
      program. The trajectories of the MD simulations were analyzed with order
      parameters such as radial atom pair distribution functions g(r), diffusion
      coefficients and root mean square deviations values. MD results suggest that
      addition of chenodeoxy cholic acid to dyes significantly reduces structural
      arrangement and increases conformational flexibility and mobility of dye
      molecules. The influence of semi-perfluorinated alkyl chains in indole dye
      molecules was analyzed. The parameters such as open-circuit voltage (V(oc)) and
      power conversion efficiency (eta) of dye-sensitized solar cells are corroborated
      with flexibility and diffusion values of dye molecules.

PMID- 21904813
TI  - A B3LYP and MP2(full) theoretical investigation into explosive sensitivity upon
      the formation of the molecule-cation interaction between the nitro group of 3,4
      dinitropyrazole and H+, Li+, Na+, Be2+ or Mg2+.
AB  - The explosive sensitivity upon the formation of molecule-cation interaction
      between the nitro group of 3,4-dinitropyrazole (DNP) and H(+), Li(+), Na(+),
      Be(2+) or Mg(2+) has been investigated using the B3LYP and MP2(full) methods with
      the 6-311++G** and 6-311++G(2df,2p) basis sets. The bond dissociation energy
      (BDE) of the C3-N7 trigger bond has also been discussed for the DNP monomer and
      the corresponding complex. The interaction between the oxygen atom of nitro group
      and H(+) in DNP...H(+) is partly covalent in nature. The molecule-cation
      interaction and bond dissociation energy of the C3-N7 trigger bond follow the
      order of DNP...Be(2+) > DNP...Mg(2+) > DNP...Li(+) > DNP...Na(+). Except for
      DNP...H(+), the increment of the trigger bond dissociation energy in comparison
      with the DNP monomer correlates well with the molecule-cation interaction energy,
      natural charge of the nitro group, electron density rho(BCP(C3-N7)),
      delocalization energy E(2) and NBO charge transfer. The analyses of atoms in
      molecules (AIM), natural bond orbital (NBO) and electron density shifts have
      shown that the electron density of the nitro group shifts toward the C3-N7
      trigger bond upon the formation of the molecule-cation interaction. Thus, the
      trigger bond is strengthened and the sensitivity of DNP is reduced.

PMID- 21904814
TI  - Efficacy of leflunomide addition in relation to prognostic factors for patients
      with active early rheumatoid arthritis failing to methotrexate in daily practice.
AB  - The recommendations of the European League Against Rheumatism (EULAR) for the
      management of rheumatoid arthritis (RA) suggest a different therapeutic approach
      to methotrexate (MTX) resistance according to the presence or absence of poor
      prognostic factors. Retrospectively, in our patients with active early RA
      (disease activity score in 28 joints (DAS28) > 3.2) that failed to respond to
      initial MTX monotherapy, we investigated whether leflunomide (LEF) addition had a
      different efficacy when associated with the presence or absence of poor
      prognostic factors. Of the 20 patients who received LEF, 15 (2 males and 13
      females) tolerated the combination. Five patients had no poor prognostic factors,
      and 4 (80%) of those patients achieved remission or low disease activity (LDA)
      according to DAS28 and also a good response with the EULAR criteria. Of the 10
      patients with at least one poor prognostic factor, remission or LDA occurred in 4
      (40%) of the patients, and a good EULAR response was obtained in 3 (30%) of the
      patients. By Fisher's exact test, no significant difference was found between the
      two groups of patients in remission or LDA (p = 0.28) according to DAS28 and a
      good response (p = 0.12) with the EULAR criteria. In all patients with an
      inadequate response to the LEF+MTX combination, the substitution of a TNF
      inhibitor for LEF or the addition of a TNF inhibitor to the combination led to
      remission or LDA. Large studies are required to investigate the efficacy of LEF
      addition in relation to prognostic factors in patients with active early RA that
      did not respond to the initial therapy with MTX alone.

PMID- 21904815
TI  - Helicobacter pylori seropositivity in fibromyalgia syndrome.

PMID- 21904816
TI  - Enhanced production of nukacin D13E in Lactococcus lactis NZ9000 by the
      additional expression of immunity genes.
AB  - Nukacin D13E (D13E) is a variant of type-A(II) lantibiotic nukacin ISK-1 produced
      by Staphylococcus warneri ISK-1. D13E exhibited a twofold higher specific
      antimicrobial activity than nukacin ISK-1 against a number of Gram-positive
      bacteria. We previously reported the heterologous production of D13E in
      Lactococcus lactis NZ9000 under the control of nisin-controlled gene expression
      system. In this study, we demonstrated enhanced production of D13E by the
      additional expression of immunity genes, nukFEG. The nukacin ISK-1 immunity,
      conferred by the ABC transporter complex, NukFEG, and the lantibiotic-binding
      protein, NukH, was not overwhelmed by D13E. The additional NukFEG resulted in a
      fourfold increase in the immunity level of the strain and a 5.2-fold increase in
      D13E production. The additional NukFEGH-expressing strain with the highest D13E
      immunity showed reduced level of production. Further improvement in D13E
      production was achieved by using pH-controlled batch fermentation.

PMID- 21904818
TI  - LOX-1/LOXIN: the yin/yang of atheroscleorosis.
AB  - Atherosclerosis is the first cause of death in industrialized countries. Together
      with traditional risk factors (male gender, hypercholesterolemia, hypertension,
      diabetes, smoking and age), non-traditional risk factors have also been described
      as predisposing to this disease. Among these, oxidized low density lipoproteins
      (OxLDL) have been described in correlation to many proatherogenic processes. Many
      of the effects of OxLDL are mediated by the lectin like oxidized low density
      lipoprotein receptor 1 (LOX-1), expressed on endothelial cells, macrophages, SMCs
      and platelets. LOX-1 is encoded by the lectin like oxidized low density
      lipoprotein receptor 1 (OLR1) gene, located in the p12.3-p13.2 region of human
      chromosome 12. Variations on this gene have been studied extensively both at the
      functional and epidemiological level. Despite the fact that functional roles for
      two variants have been demonstrated, the epidemiological studies have provided
      inconsistent and inconclusive results. Of particular interest, it has been
      demonstrated that a linkage disequilibirum block of SNPs located in the intronic
      sequence of the OLR1 gene modulates the alternative splicing of OLR1 mRNA,
      leading to different ratios of LOX-1 full receptor and LOXIN, an isoform lacking
      part of the functional domain. As demonstrated, LOXIN acts by blocking the
      negative effective of LOX-1 activation. Here we review the state of the art
      regarding LOX-1, LOXIN, and the functional effects that are associated with the
      interaction of these molecules.

PMID- 21904819
TI  - The effects of acute doses of nicotine on video lottery terminal gambling in
      daily smokers.
AB  - RATIONALE: A growing body of evidence suggests that gambling frequently co-occurs
      with smoking, yet little is known about the degree to which nicotine and/or
      tobacco use influences gambling behavior. Nonetheless, an increasing number of
      studies suggest that acute administration of nicotine may alter other reinforcing
      behaviors in both animal and human models, raising the possibility that nicotine
      may also influence gambling behavior and craving. OBJECTIVES: The purpose of this
      study was to examine the acute effects of nicotine on subjective and behavioral
      gambling responses. METHODS: Twenty-eight (15 male) regular gamblers who smoke
      daily completed two double-blind laboratory sessions where their subjective and
      behavioral responses to video lottery terminal (VLT) gambling were assessed,
      following the administration of nicotine inhalers (NI; 4 mg deliverable) or
      placebo inhalers. RESULTS: NI significantly decreased tobacco-related cravings (p
      < 0.05) but did not affect gambling-related cravings, VLT betting patterns, or
      subjective responses (ps > 0.1). CONCLUSIONS: NI were found to acutely suppress
      tobacco-related cravings without influencing gambling. These results suggest that
      use of nicotine replacement therapies may be a safe option for gamblers who are
      attempting to quit smoking.

PMID- 21904817
TI  - Exploiting bacterial DNA gyrase as a drug target: current state and perspectives.
AB  - DNA gyrase is a type II topoisomerase that can introduce negative supercoils into
      DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent
      from higher eukaryotes, making it an attractive target for antibacterials. The
      fluoroquinolones are examples of very successful gyrase-targeted drugs, but the
      rise in bacterial resistance to these agents means that we not only need to seek
      new compounds, but also new modes of inhibition of this enzyme. We review known
      gyrase-specific drugs and toxins and assess the prospects for developing new
      antibacterials targeted to this enzyme.

PMID- 21904820
TI  - Synergistic interaction between baclofen administration into the median raphe
      nucleus and inconsequential visual stimuli on investigatory behavior of rats.
AB  - RATIONALE: Noncontingent administration of amphetamine into the ventral striatum
      or systemic nicotine increases responses rewarded by inconsequential visual
      stimuli. When these drugs are contingently administered, rats learn to self
      administer them. We recently found that rats self-administer the GABA(B) receptor
      agonist baclofen into the median (MR) or dorsal (DR) raphe nuclei. OBJECTIVES: We
      examined whether noncontingent administration of baclofen into the MR or DR
      increases rats' investigatory behavior rewarded by a flash of light. RESULTS:
      Contingent presentations of a flash of light slightly increased lever presses.
      Whereas noncontingent administration of baclofen into the MR or DR did not
      reliably increase lever presses in the absence of visual stimulus reward, the
      same manipulation markedly increased lever presses rewarded by the visual
      stimulus. Heightened locomotor activity induced by intraperitoneal injections of
      amphetamine (3 mg/kg) failed to concur with increased lever pressing for the
      visual stimulus. These results indicate that the observed enhancement of visual
      stimulus seeking is distinct from an enhancement of general locomotor activity.
      Visual stimulus seeking decreased when baclofen was co-administered with the
      GABA(B) receptor antagonist, SCH 50911, confirming the involvement of local
      GABA(B) receptors. Seeking for visual stimulus also abated when baclofen
      administration was preceded by intraperitoneal injections of the dopamine
      antagonist, SCH 23390 (0.025 mg/kg), suggesting enhanced visual stimulus seeking
      depends on intact dopamine signals. CONCLUSIONS: Baclofen administration into the
      MR or DR increased investigatory behavior induced by visual stimuli. Stimulation
      of GABA(B) receptors in the MR and DR appears to disinhibit the motivational
      process involving stimulus-approach responses.

PMID- 21904822
TI  - Antidromic potential spread modulates the receptor responses in the stretch
      receptor neurons of the crayfish.
AB  - The effects of antidromic potential spread were investigated in the stretch
      receptor neurons of the crayfish. Current and potential responses to conductance
      changes were recorded in the dynamic clamp condition and compared to those
      obtained by using some conventional clamp methods and a compartmental neuron
      model. An analogue circuit was used for dynamic calculation of the injected
      receptor current as a function of the membrane potential and the given
      conductance change. Alternatively, receptor current responses to a mechanical
      stimulus were recorded and compared when the cell was voltage clamped to a
      previously recorded impulse wave form and the resting potential, respectively.
      Under dynamic clamp, the receptor current had an oscillating waveform which
      contrasts with the conventional recordings. Frequency, amplitude and sign of the
      oscillations were dependent on the applied conductance level, reversal potential
      and electrotonic attenuation. Mean current amplitude and frequency of the evoked
      impulse responses were smaller under dynamic clamp, especially for large
      conductance increases. However, firing frequency was larger if plotted against
      the mean current response. Recorded responses were similar to those calculated in
      the model. It was not possible to evoke any adaptation in the slowly adapting
      neuron by using the dynamic clamp. Evoked potential change served as a self
      limiting response, preventing the depolarization block. However, impulse duration
      was significantly shorter in the rapidly adapting neuron when the dynamic clamp
      was used. It was concluded that, in the stretch receptor neurons during a
      conductance increase, antidromic potential spread modulates the receptor
      responses and contributes to adaptation.

PMID- 21904821
TI  - Calcium-dependent inhibition of T-type calcium channels by TRPV1 activation in
      rat sensory neurons.
AB  - We studied the inhibitory effects of transient receptor potential vanilloid-1
      (TRPV1) activation by capsaicin on low-voltage-activated (LVA, T-type) Ca(2+)
      channel and high-voltage-activated (HVA; L, N, P/Q, R) currents in rat DRG
      sensory neurons, as a potential mechanism underlying capsaicin-induced analgesia.
      T-type and HVA currents were elicited in whole-cell clamped DRG neurons using
      ramp commands applied before and after 30-s exposures to 1 MUM capsaicin. T-type
      currents were estimated at the first peak of the I-V characteristics and HVA at
      the second peak, occurring at more positive potentials. Small and medium-sized
      DRG neurons responded to capsaicin producing transient inward currents of
      variable amplitudes, mainly carried by Ca(2+). In those cells responding to
      capsaicin with a large Ca(2+) influx (59% of the total), a marked inhibition of
      both T-type and HVA Ca(2+) currents was observed. The percentage of T-type and
      HVA channel inhibition was prevented by replacing Ca(2+) with Ba(2+) during
      capsaicin application or applying high doses of intracellular BAPTA (20 mM),
      suggesting that TRPV1-mediated inhibition of T-type and HVA channels is Ca(2+)
      dependent and likely confined to membrane nano-microdomains. Our data are
      consistent with the idea that TRPV1-induced analgesia may derive from indirect
      inhibition of both T-type and HVA channels which, in turn, would reduce the
      threshold of nociceptive signals generation (T-type channel inhibition) and
      nociceptive synaptic transmission (HVA-channels inhibition).

PMID- 21904823
TI  - Protein:carbohydrate ratios explain life span patterns found in Queensland fruit
      fly on diets varying in yeast:sugar ratios.
AB  - Dietary restriction extends life span across a vast diversity of taxa, but
      significant challenges remain in elucidating the underlying mechanisms.
      Distinguishing between caloric and nutrient effects is an essential step. Recent
      studies with Drosophila and tephritid fruit flies have reported increased life
      span as dietary yeast-to-sugar ratios decreased and these effects have been
      attributed to changes in protein-to-carbohydrate (P:C) ratios of the diets rather
      than calories. However, yeast is a complex mix of macronutrients and
      micronutrients, and hence changes in yeast content of the diet necessarily alters
      other nutrients in lockstep. To explicitly test whether studies using yeast are
      justified in attributing results to diet protein content rather than correlated
      nutrients, we developed a chemically defined diet allowing manipulation of just
      the ratio of protein (free amino acids) to carbohydrate (sucrose) levels of diets
      while holding other nutrients constant. Mated, female Queensland fruit flies (Q
      flies) were fed 1 of 18 diets varying in P:C ratios and diet concentration. Diet
      consumption, egg production, and life span were recorded for each fly. In close
      concordance with recent studies using yeast diets, flies had increased life span
      as P:C ratios decreased, and caloric restriction did not extend life span.
      Similarly, egg production was maximized on high P:C ratios, but lifetime egg
      production was maximized on intermediate P:C ratios, indicating a life history
      trade-off between life span and egg production rate. Finally, Q-flies adjusted
      their diet intake in response to P:C ratios and diet concentration. Our results
      substantiate recent claims that P:C ratios significantly modulate life span in
      flies.

PMID- 21904824
TI  - Survival features of EBV-stabilized cells from centenarians: morpho-functional
      and transcriptomic analyses.
AB  - In the present work, we analyzed the survival features of six different Epstein
      Barr virus (EBV)-stabilized lymphoid cell lines obtained from adult subjects and
      from subjects of more than 95 years. For the first, we found that lymphoid B
      cells from centenarians were more resistant to apoptosis induction and displayed
      a more developed lysosomal compartment, the most critical component of phagic
      machinery, in comparison with lymphoid B cells from adult subjects. In addition,
      cells from centenarians were capable of engulfing and digesting other cells,
      i.e., their siblings (even entire cells), whereas lymphoid cells from "control
      samples", i.e., from adults, did not. This behavior was improved by nutrient
      deprivation but, strikingly, it was unaffected by the autophagy-modulating drug,
      rapamycin, an autophagy inducer, and 3-methyladenine, an autophagy inhibitor.
      Transcriptomic analyses indicated that: (1) aspartyl proteases, (2) cell surface
      molecules such as integrins and cadherins, and (3) some components of
      cytoskeletal network could contribute to establish this survival phenotype. Also,
      Kyoto Encyclopedia of Genes and Genomes pathways such as Wnt signaling pathway,
      an essential contributor to cell migration and actin cytoskeleton remodeling,
      appeared as prominent. Although we cannot rule out the possibility that EBV
      immortalization could play a role, since we observed this phagic behavior in
      cells from centenarians but not in those from adults, we hypothesize that it may
      represent an important survival determinant in cells from centenarians.

PMID- 21904825
TI  - Bone development in the fetus and neonate: role of the calciotropic hormones.
AB  - During embryonic and fetal development much of the skeleton initiates as a
      cartilaginous scaffold, which is progressively resorbed and replaced by bone.
      Endochondral bone formation continues until the growth plates fuse during
      puberty. At all life stages adequate delivery of mineral is required for the
      skeleton to achieve and maintain appropriate mineral content and strength. During
      fetal development the placenta actively transports calcium, phosphorus, and
      magnesium. Postnatally passive and then active absorption from the intestines
      becomes the main supply of minerals to the skeleton. Animal and human data
      indicate that fetal bone development requires parathyroid hormone (PTH) and PTH
      related protein but not vitamin D/calcitriol, calcitonin, or (possibly) sex
      steroids. During the postnatal period, when intestinal calcium absorption becomes
      an active process, skeletal development begins to depend upon vitamin
      D/calcitriol but this requirement can be bypassed by increasing the calcium
      content of the diet or by administering intermittent calcium infusions.

PMID- 21904826
TI  - Periodic expression of Sm proteins parallels formation of nuclear Cajal bodies
      and cytoplasmic snRNP-rich bodies.
AB  - Small nuclear ribonucleoproteins (snRNPs) play a fundamental role in pre-mRNA
      processing in the nucleus. The biogenesis of snRNPs involves a sequence of events
      that occurs in both the nucleus and cytoplasm. Despite the wealth of biochemical
      information about the cytoplasmic assembly of snRNPs, little is known about the
      spatial organization of snRNPs in the cytoplasm. In the cytoplasm of larch
      microsporocytes, a cyclic appearance of bodies containing small nuclear RNA
      (snRNA) and Sm proteins was observed during anther meiosis. We observed a
      correlation between the occurrence of cytoplasmic snRNP bodies, the levels of Sm
      proteins, and the dynamic formation of Cajal bodies. Larch microsporocytes were
      used for these studies. This model is characterized by natural fluctuations in
      the level of RNA metabolism, in which periods of high transcriptional activity
      are separated from periods of low transcriptional activity. In designing
      experiments, the authors considered the differences between the nuclear and
      cytoplasmic phases of snRNP maturation and generated a hypothesis about the
      direct participation of Sm proteins in a molecular switch triggering the
      formation of Cajal bodies.

PMID- 21904828
TI  - Childhood conduct problems are associated with increased partnership and
      parenting difficulties in adulthood.
AB  - This paper uses data from a sample of 337 parents studied at age 30 to examine
      the linkages between childhood conduct problems assessed at ages 7-9 and later
      partnership and parenting outcomes. The key findings of this study were: 1)
      increasing levels of childhood conduct problems were associated with increased
      risk of partnership difficulties, including relationship ambiguity, inter-partner
      conflict/violence and lower levels of relationship satisfaction; 2) increasing
      levels of childhood conduct problems were associated with increased risk of
      parenting difficulties, including over-reactivity, lax and inconsistent
      discipline, child physical punishment and lower levels of parental warmth and
      sensitivity. These findings were consistent across both parent reports and
      interviewer ratings, and in nearly all cases remained after extensive adjustment
      for confounding and selection bias. Study findings add to the growing body of
      evidence documenting the adverse consequences of early conduct problems for later
      adult interpersonal relationships and parenting behaviors.

PMID- 21904829
TI  - Relationship between clinical sinusitis symptoms and sinus CT severity in
      pediatric post bone marrow transplant and immunocompetent patients.
AB  - Since typical inflammatory responses may be diminished in children following bone
      marrow transplant (BMT), computed tomography (CT) imaging of the sinuses has been
      increasingly ordered to diagnose sinusitis in this group. The objective of this
      study was to determine the association between clinical sinusitis symptoms and
      sinus opacification on CT scans in post BMT versus immunocompetent children. Our
      sample was comprised of 64 post BMT and 86 immunocompetent children with sinus CT
      scans. CT sinus opacification was scored using the modified Lund-Mackay staging
      system. The relationship between clinical sinusitis symptoms (rhinorrhea, nasal
      congestion, cough, headache, and facial pain) and opacification was compared for
      the two groups. The severity of sinus opacification in the BMT group was
      significantly higher compared to the immunocompetent group. In combined patient
      groups the odds ratio (OR) for moderate/severe sinusitis was significantly
      elevated for rhinorrhea (OR = 3.00; 95% confidence interval [CI], 1.27-7.12),
      cough (OR = 2.80; 95% CI, 1.22-6.42), and having either rhinorrhea, nasal
      congestion, or cough (OR = 4.76; 95% CI, 1.71-13.24). While the immunocompetent
      group had a greater number of sinusitis symptoms compared to the post BMT group,
      both groups had a significant increase in the severity on CT with increasing
      number of symptoms. CONCLUSION: In post BMT patients, our data demonstrated
      higher odds of moderate/severe sinusitis on CT scans associated with rhinorrhea,
      cough or nasal congestion. These finding suggest that in post BMT children,
      detailed sinus history may still play a vital role in the diagnosis of sinusitis.

PMID- 21904831
TI  - Novel targets for cancer and connective tissues diseases: A meeting sponsored by
      the International CCN Society : Coast Coal Harbour Hotel, Vancouver, BC, Canada
      (September 24-27, 2011).

PMID- 21904832
TI  - The clot burden score, the Boston Acute Stroke Imaging Scale, the cerebral blood
      volume ASPECTS, and two novel imaging parameters in the prediction of clinical
      outcome of ischemic stroke patients receiving intravenous thrombolytic therapy.
AB  - INTRODUCTION: Recently two classification methods based on the location and the
      extent of thrombosis detected with CT angiography have been introduced: the
      Boston Acute Stroke Imaging Scale (BASIS) and the clot burden score (CBS). We
      studied the performance of BASIS and CBS in predicting good clinical outcome (mRS
      <= 2 at 90 days) in an acute (< 3 h) stroke cohort treated with intravenous
      thrombolytic therapy. METHODS: Eighty-three consecutive patients who underwent
      multimodal CT were analyzed. Binary logistic regression model was used to assess
      how BASIS, CBS, and cerebral blood volume (CBV) ASPECTS predict favorable
      clinical outcome. Diagnostic sensitivities and specificities were calculated and
      compared. RESULTS: Patients with low CBS and CBV ASPECTS scores and major strokes
      according to BASIS had significantly higher admission NIHSS scores, larger
      perfusion defects, and more often poor clinical outcome. In logistic regression
      analysis, CBV ASPECTS, CBS and BASIS were significantly associated with the
      clinical outcome. The performance of BASIS improved when patients with thrombosis
      of the M2 segment of the middle cerebral artery were classified as having minor
      stroke (M1-BASIS). In the anterior circulation, the sum of CBS and CBV ASPECTS
      (CBSV) proved to be the most robust predictor of favorable outcome. CBV ASPECTS
      and CBS had high sensitivity but moderate to poor specificity while BASIS was
      only moderately sensitive and specific. CONCLUSION: CBS, BASIS, and CBV ASPECTS
      are statistically robust and sensitive but unspecific predictors of good clinical
      outcome. Two new derived imaging parameters, CBSV and M1-BASIS, share these
      properties and may have increased prognostic value.

PMID- 21904830
TI  - Ultrasound and colour Doppler in infantile subglottic haemangioma.
AB  - BACKGROUND: Subglottic haemangioma causes progressive and life-threatening
      stridor, typically manifesting at age 2-3 months. Standard diagnosis is by
      laryngoscopy. Larynx sonography is rarely used but allows assessment of the
      presence and extension of a mass that impinges on the subglottic airway. The
      additional use of colour Doppler enables demonstration of the vascular nature of
      such masses. OBJECTIVE: To compare US and endoscopic findings in infants with
      subglottic haemangioma and to evaluate accuracy of US and colour Doppler imaging
      in this diagnosis. MATERIALS AND METHODS: We report eight infants with subglottic
      haemangioma seen in our institution over the last decade. They presented with
      laryngeal stridor and were all investigated with both US and endoscopy. Six
      infants underwent colour Doppler sonography. RESULTS: US and endoscopic findings
      showed excellent anatomical correlation in lateral subglottic haemangioma. Colour
      Doppler imaging was deemed helpful in four infants. CONCLUSION: Larynx sonography
      with complementary colour Doppler imaging was non-invasive and helpful in the
      diagnosis of subglottic haemangioma.

PMID- 21904833
TI  - Trimodal endoscopic imaging for the detection and differentiation of colorectal
      adenomas: a prospective single-centre clinical evaluation.
AB  - PURPOSE: The purpose of this study is to evaluate an endoscopic trimodal imaging
      (ETMI) system (high resolution, autofluorescence, and NBI) in the detection and
      differentiation of colorectal adenomas. METHODS: A prospective randomised trial
      of tandem colonoscopies was carried out using the Olympus XCF-FH260AZI system.
      Each colonic segment was examined twice for lesions, once with HRE and once with
      AFI, in random order per patient. All detected lesions were assessed with NBI for
      pit pattern and with AFI for colour. All lesions were removed and sent for
      histology. Any lesion identified on the second examination was considered as
      missed by the first examination. Outcome measures are adenoma miss rates of AFI
      and HRE, and diagnostic accuracy of NBI and AFI for differentiating neoplastic
      from non-neoplastic lesions. RESULTS: Ninety-four patients underwent colonoscopy
      with ETMI (47 in each group). Among 47 patients examined with AFI first, 31
      adenomas in 15 patients were detected initially [detection rate 0.66 (0.52
      0.75)]. Subsequent HRE inspection identified six additional adenomas. Among 47
      patients examined with HRE first, 29 adenomas in 14 patients were detected
      initially [detection rate 0.62 (0.53-0.79)]. Successive AFI yielded seven
      additional adenomas. Adenoma miss rates of AFI and HRE were 14% and 16.2%,
      respectively (p = 0.29). Accuracy of AFI alone for differentiation was lower than
      NBI (63% vs. 80%, p < 0.001). Combined use of AFI and NBI achieved improved
      accuracy for differentiation (84%), showing a trend for superiority compared with
      NBI alone (p = 0.064). CONCLUSIONS: AFI did not significantly reduce the adenoma
      miss rate compared with HRE. AFI alone had a disappointing accuracy for adenoma
      differentiation, which could be improved by combination of AFI and NBI.

PMID- 21904835
TI  - [Congenital and endogenous endocrine myopathy].
AB  - Disorders in endocrinological pathways rarely lead to manifest acquired or
      endogenous myopathy so that an interdisciplinary evaluation between neurology and
      endocrinology is essential for these disorders. Asymptomatic or forme fruste
      variants may be more common and even underdiagnosed in these circumstances.
      Dysbalance disorders of protein synthesis, electrolytes and carbohydrates can
      lead to several rare forms of myopathy due to the dependence on hormonal
      metabolism. In general, the main neuromuscular symptom is proximal weakness,
      sometimes in addition to myalgia and muscle atrophy. Endocrine myopathies are
      usually reversible by treatment of the underlying disease. The severity of the
      endocrinopathy is of fundamental importance for the long-term clinical outcome.

PMID- 21904834
TI  - Malignant tumor-like gastric lesion due to Candida albicans in a diabetic patient
      treated with cyclosporin: a case report and review of the literature.
AB  - The gastrointestinal tract of healthy individuals is colonized by hundreds of
      saprophytes and mycetes, especially the Candida species, are habitual ones. Under
      certain conditions, the fungal flora may overgrow, resulting in lesions of the
      digestive mucosa which, rarely, can have a local diffusion and/or spread to the
      lympho-hematogenous system. Mycotic infections of the stomach can sometimes look
      like benign gastric ulcers. Here, we present the case report of a woman, aged 64,
      who presented with type II diabetes mellitus and psoriasis, on chronic treatment
      with cyclosporin A and with endoscopic evidence of an ulcerated, vegetating
      gastric lesion secondary to Candida albicans infection. Although strongly
      suggestive of malignancy, it completely healed after cyclosporin withdrawal and
      the administration of oral antifungal drugs.

PMID- 21904836
TI  - Genetic variants of MnSOD and GPX1 and susceptibility to bladder cancer in a
      Turkish population.
AB  - This study was conducted to investigate the association of genetic polymorphisms
      in the MnSOD and GPX1 genes with the risk and invasiveness of bladder cancer in a
      Turkish population. This prospectively designed study enrolled 157 patients with
      bladder cancer (mean age 63.2 +/- 10.86 years) and 224 healthy controls (mean age
      61.7 +/- 8.39 years). Genotyping of the MnSOD Ala-9Val and GPX1 Pro198Leu
      polymorphisms was carried out by PCR-RFLP. No significant difference was found in
      MnSOD genotype distributions between the controls and the bladder cancer
      patients. However, the Leu/Leu genotype of GPX1 was associated with a
      significantly higher risk of bladder cancer than the Pro/Pro genotype. When
      stratified according to tumor stage, the Leu/Leu genotype of GPX1 was more
      frequently observed in bladder cancer patients with high-stage tumors than those
      with low-stage tumors. Additionally, patients carrying both Ala/Ala of MnSOD and
      Leu/Leu of GPX1 had the highest risk of developing bladder cancer. In conclusion,
      the present study indicates that the GPX1 Pro198Leu polymorphism may be
      associated with the risk and development of invasive bladder cancer. In addition,
      the combination of the MnSOD Ala/Ala and GPX1 Leu/Leu genotypes may have a
      synergistic effect on disease risk.

PMID- 21904837
TI  - [Stereometric parameters of the optic disc. Comparison between a simultaneous non
      mydriatic stereoscopic fundus camera (KOWA WX 3D) and the Heidelberg scanning
      laser ophthalmoscope (HRT IIII)].
AB  - BACKGROUND: The Heidelberg retina tomograph (HRTIII, Heidelberg Engineering,
      Germany) in conjunction with the Moorfields regression analysis (MRA) allows
      monitoring for the progression of early damage to the optic nerve suspicious of
      early stage glaucoma. The confocal scanning laser ophthalmoscope provides
      clinicians with an objective and reproducible analysis of morphological
      parameters of the optic disc. Margins of the optic disc are approximated with a
      contour line to calculate the stereometric parameters leading to interobserver
      and intraobserver variability of the MRA. New devices enabling 3D fundus
      photography might be an alternative to the established HRT. It was the goal of
      this study to compare the methods by assessing the differences in the topographic
      parameters obtained by the HRT and the Kowa nonmyd WX 3D (2D/3D non-mydriatic
      retinal camera, Kowa, Japan) in a representative sample. METHODS: This
      retrospective study included 45 eyes of normal patients, 40 eyes of patients with
      macropapillae and 45 eyes of glaucoma patients. Each patient underwent an HRT
      examination and fundus photography with the Kowa nonmyd WX 3D on the same day.
      Excluded from the study were eyes with hazy media (cornea, lens, vitreous) or
      refractive anomalies higher than >4 dpt or astigmatisms >2 dpt. Eyes with
      previous refractive surgery history or other retinal diseases affecting the optic
      nerve were also excluded from the study. Bland-Altman plots were used for
      statistical evaluation. Distribution of parameters was described by 95%
      confidence intervals (CI). RESULTS: In normal eyes (n=45) a mean difference in
      the disc area of 0.33 mm(2) was found (95 % confidence interval CI: 0.22-0.43),
      in the cup-disc ratio (CDR) of 0.02 (95% CI: -0.06-0.14), in the cup volume of
      0.03 mm(3) (95% CI: -0.04-0.01), in the rim volume of 0.04 mm(3) (95%-CI: -0.04
      0.13) and in the maximum cup depth of 0.28 mm (95 %-CI: 0.34-0.23). All
      differences, except for the rim volume, were statistically significant (p<0.05).
      Patients exhibiting a macropapilla (n=40) displayed a mean difference of 0.03
      mm(2) (95 % CI: -0.18-0.11) for the disc area, a difference in CDR of 0.09 (95%
      CI: -0.05-0.13), a difference in maximum cup depth of 0.28 mm (95% CI: 0.23-0.34)
      and a cup volume of 0.14 mm(3) (95%-CI: 0.10-0.18). In addition, there were no
      significant differences in rim volume (difference: -0.02 mm(3), 95% CI: -0.07
      0.12) or in disc area. In glaucomatous eyes (n=45), the mean difference for cup
      area was 0.33 mm(2) (95% CI: 0.22-0.43), an area of 0.09 mm(2) (95% CI: 0.06
      0.13) for the CDR, -0.03 mm(3) (95 % CI: -0.09-0.02) for the cup volume and 0.08
      mm(3) (95% CI: 0.03-0.13) for the rim volume. Mean maximum cup depth difference
      was 0.25 mm (95% CI: 0.20-0.31). Mean differences in CDR, maximum cup depth and
      cup area were all statistically significant. The mean differences did not exceed
      the interobserver and intraobserver variability found in HRT measurements of
      other studies. CONCLUSIONS: To the best of our knowledge this study is the first
      comparing optic disc parameters of HRT and 3D photography. Mean differences in
      stereometric parameters did not exceed the known interobserver and intraobserver
      variability. The combination of non-mydriatic fundus photography and optic disc
      analysis is a very attractive and time-saving method. However, before progression
      of early glaucoma can be monitored or suspected glaucoma can be appraised over
      longer time periods, further studies are needed to clarify test and retest
      variability.

PMID- 21904838
TI  - [Blind spot enlargement syndrome in acute zonal occult outer retinopathy with
      detection of autoantibodies against the retinal antigens CRALBP and S-Ag].
AB  - Acute zonal occult outer retinopathy (AZOOR) is a rare disease and is part of the
      white dot syndrome occurring bilaterally and often asymmetrically in young
      healthy myopic women. Characteristic findings are distinct focal lesions of the
      outer segments (OS) of the photoreceptor (PR) layer and abnormalities in fundus
      autofluorescence (FAF) within the lesions. Currently there is a lack of defined
      disease criteria, such as specific laboratory findings. Also no effective therapy
      is known which makes it difficult to diagnose, differentiate and treat AZOOR.
      Supplementation of antioxidants may become part of therapeutic options in AZOOR.
      A 19-year-old myopic woman presented with unilaterally reduced visual acuity. Due
      to the clinical features and with the help of FAF, spectral domain optical
      coherence tomography (SD-OCT) and perimetry the diagnosis of blind spot
      enlargement syndrome in AZOOR was made. Identification of autoantibodies specific
      for two retinal antigens (CRALBP and S-Ag) supports the concept of an
      autoimmunological origin of the disease. Systemic steroids were given but stopped
      almost 6 weeks later as no improvement was seen. In follow-up controls over 12
      months the clinical picture remained unchanged without any further therapy.

PMID- 21904839
TI  - Improvement of bowel dysfunction with sacral neuromodulation for refractory urge
      urinary incontinence.
AB  - INTRODUCTION AND HYPOTHESIS: Sacral nerve stimulation (SNS) is approved for
      urologic indications in the USA and, recently, fecal incontinence. This study
      described concomitant bowel dysfunction and improvements in bowel and urinary
      symptoms and quality of life (QOL) in women with refractory urge urinary
      incontinence (UUI) receiving SNS. METHODS: Women (N = 36) with refractory UUI
      receiving SNS were prospectively enrolled. Surveys and exams were completed at
      baseline and follow-up, with symptom and QOL scores measured using validated
      scales (0-100, none-worst). RESULTS: A total 24 women were followed up at a
      median of 4.0 months post-implantation. Of these, 20 (83%) had bowel dysfunction,
      13 (54%) used bowel medications at baseline, and 11 (45%) continued them after
      SNS. The mean/median urinary (54.8 to 32.6) and bowel (23.4 to 14.1) symptom
      scores improved significantly, as did urinary (64.2 to 14.3) but not bowel (2.4
      to 0.0) QOL scores. CONCLUSIONS: Bowel dysfunction is common in women with
      refractory UUI. SNS improves urinary symptoms and QOL, but improvement in bowel
      symptoms does not translate into significant QOL changes.

PMID- 21904841
TI  - Presence of endothelial colony-forming cells is associated with reduced
      microvascular obstruction limiting infarct size and left ventricular remodelling
      in patients with acute myocardial infarction.
AB  - Endothelial colony-forming cells (ECFCs) are known to increase after acute
      myocardial infarction (AMI). We examined whether the presence of ECFCs is
      associated with preserved microvascular integrity in the myocardium at risk by
      reducing microvascular obstruction (MVO). We enrolled 88 patients with a first ST
      elevation AMI. ECFC colonies and circulating progenitor cells were characterized
      at admission. MVO was evaluated at 5 days and infarct size at 5 days and at 6
      month follow-up by magnetic resonance imaging. ECFC colonies were detected in 40
      patients (ECFC(pos) patients). At 5 days, MVO was of greater magnitude in
      ECFC(neg) versus ECFC(pos) patients (7.7 +/- 5.3 vs. 3.2 +/- 5%, p = 0.0002). At
      6 months, in ECFC(pos) patients, there was a greater reduction in infarct size (
      32.4 +/- 33 vs. -12.8 +/- 24%; p = 0.003) and a significant improvement in left
      ventricular (LV) volumes and ejection fraction. Level of circulating CD34+/VEGF
      R2+ cells was correlated with the number of ECFC colonies (r = 0.54, p < 0.001)
      and relative change in infarct size (r = 0.71, p < 0.0001). The results showed
      that the presence of ECFC colonies is associated with reduced MVO after AMI,
      leading to reduced infarct size and less LV remodelling and can be considered a
      marker of preserved microvascular integrity in AMI patients.

PMID- 21904840
TI  - Impact of intravesical hyaluronic acid and chondroitin sulfate on bladder pain
      syndrome/interstitial cystitis.
AB  - INTRODUCTION AND HYPOTHESIS: Intravesical instillations of hyaluronic acid (HA)
      and chondroitin sulfate (CS) may lead to regeneration of the damaged
      glycosaminoglycan layer in interstitial cystitis/bladder pain syndrome (IC/BPS).
      METHODS: Twenty-two patients with IC/BPS received intravesical instillations (40
      ml) of sodium HA 1.6% and CS 2.0% in 0.9% saline solution (IALURIL, IBSA) once
      weekly for 8 weeks, then once every 2 weeks for the next 6 months. RESULTS: The
      score for urgency was reduced from 6.5 to 3.6 (p = 0.0001), with a reduction in
      pain scores from an average of 5.6 to 3.2 (p = 0.0001). The average urine volume
      increased from 129.7 to 162 ml (p < 0.0001), with a reduction in the number of
      voids in 24 h, from 14 to 11.6 (p < 0.0001). The IC Symptom and Problem Index
      decreased from 25.7 to 20.3 (p < 0.0001), and the Pain Urgency Frequency score,
      from 18.7 to 12.8 (p < 0.0001). CONCLUSION: The treatment appeared to be
      effective and well tolerated in IC/BPS in this initial experience.

PMID- 21904842
TI  - Thrombotic complications in multiple myeloma: a report of three cases and review
      of the literature.
AB  - The risk of venous thromboembolism (VTE) increases in the presence of plasma cell
      dyscrasias. Monoclonal gammopathy of undetermined significance (MGUS) and
      multiple myeloma (MM) share an intrinsic increased risk of VTE. Treatment with
      thalidomide and lenalidomide further increases the incidence of VTE in certain MM
      patient subsets. The pathogenesis remains unclear, but probably involves several
      factors such as activation of procoagulant factors, acquired activated protein C
      resistance, and inflammation. In addition to general risk factors for VTE, such
      as older age, immobility, surgery, and inherited thrombophilia, there are some MM
      specific and treatment-related factors that contribute to the increased risk. The
      risk for VTE is high under treatment with thalidomide or lenalidomide in
      combination with dexamethasone or multi-agent chemotherapy. We report 3 cases of
      MM with VTE with review of the literature. This review highlights the risk
      factors for VTE in MM and general, disease-specific and treatment-related
      mechanisms for thrombosis.

PMID- 21904843
TI  - Acute kidney injury as the first sign of spontaneous renal vein thrombosis:
      report of 2 cases.
AB  - Spontaneous renal vein thrombosis (RVT) is very rare in the absence of nephrotic
      syndrome. It is more common in newborns and infants. RVT should always be
      included in the differential diagnosis of flank pain and hematuria, and because
      RVT can induce acute renal injury. A 19-year-old man was admitted to our hospital
      because he complained of right flank pain and oliguria for 3 days. Another
      patient, a 24-year-old man, complained of a severe and sudden onset of bilateral
      flank pain and anuria for a day. They were both healthy before they developed the
      described symptoms and had different levels of decrease in renal function when
      they visited the hospital. Color Doppler ultrasonography revealed RVT in both the
      patients. The patients received therapy, including anticoagulation and
      thrombolysis, following their diagnoses, and they recovered in a few days.

PMID- 21904844
TI  - The reciprocal ledge closing wedge osteotomy for post traumatic coxa vara.
AB  - To report a proximal femoral osteotomy with retention of bone ledges in a
      reciprocal position to increase bone contact and stability. The method was
      applied to 5 patients over a 3-year period. All patients had coxa vara. The
      average length gained was 1.5 cm, and the average neck shaft angle improvement
      was 30 degrees . The Harris hip score improved from an average of 63 to 82. The
      reciprocal ledge osteotomy is technically less demanding and also allows
      conversion of normal shear forces around the upper femur to stabilizing forces.
      This method allows easier use of the DHS implant as potential rotation about the
      axis of the screw is negated by the ledges and the dynamic forces.

PMID- 21904845
TI  - Mining and validation of pyrosequenced simple sequence repeats (SSRs) from
      American cranberry (Vaccinium macrocarpon Ait.).
AB  - The American cranberry (Vaccinium macrocarpon Ait.) is a major commercial fruit
      crop in North America, but limited genetic resources have been developed for the
      species. Furthermore, the paucity of codominant DNA markers has hampered the
      advance of genetic research in cranberry and the Ericaceae family in general.
      Therefore, we used Roche 454 sequencing technology to perform low-coverage whole
      genome shotgun sequencing of the cranberry cultivar 'HyRed'. After de novo
      assembly, the obtained sequence covered 266.3 Mb of the estimated 540-590 Mb in
      cranberry genome. A total of 107,244 SSR loci were detected with an overall
      density across the genome of 403 SSR/Mb. The AG repeat was the most frequent
      motif in cranberry accounting for 35% of all SSRs and together with AAG and AAAT
      accounted for 46% of all loci discovered. To validate the SSR loci, we designed
      96 primer-pairs using contig sequence data containing perfect SSR repeats, and
      studied the genetic diversity of 25 cranberry genotypes. We identified 48
      polymorphic SSR loci with 2-15 alleles per locus for a total of 323 alleles in
      the 25 cranberry genotypes. Genetic clustering by principal coordinates and
      genetic structure analyzes confirmed the heterogeneous nature of cranberries. The
      parentage composition of several hybrid cultivars was evident from the structure
      analyzes. Whole genome shotgun 454 sequencing was a cost-effective and efficient
      way to identify numerous SSR repeats in the cranberry sequence for marker
      development.

PMID- 21904846
TI  - Development of marker sets useful in the early selection of Ren4 powdery mildew
      resistance and seedlessness for table and raisin grape breeding.
AB  - The single, dominant powdery mildew resistance locus Ren4 from Vitis romanetii
      prevents hyphal growth by Erysiphe necator. Previously, we showed that when
      introgressed into V. vinifera in the modified BC(2) population 03-3004, Ren4 was
      linked with the simple sequence repeat marker VMC7f2 on chromosome 18-a marker
      that is associated with multiple disease resistance and seedlessness. However, in
      the current study, this marker was monomorphic in related breeding populations 05
      3010 and 07-3553. To enhance marker-assisted selection at this locus, we
      developed multiplexed SNP markers using three approaches: conversion of bulked
      segregant analysis AFLP markers, sequencing of candidate genes and regions
      flanking known V. vinifera SNPs, and hybridization to the Vitis9KSNP genotyping
      array. The Vitis9KSNP array was more cost-efficient than all other approaches
      tested for marker discovery and genotyping, enabling the genotyping of 1317
      informative SNPs within the span of 1 week and at a cost of 11 cents per SNP.
      From a total of 1,446 high quality, informative markers segregating in 03-3004,
      we developed a haplotype signature of 15 multiplexed SNP markers linked with Ren4
      in 03-3004, 5 of which were linked in 05-3010, and 6 of which were linked in 07
      3553. Two of these populations segregated for seedlessness, which was tightly
      linked with Ren4 in 03-3004 (2 cM) but not in 05-3010 (22 cM). Chromosomal
      rearrangements were detected among these three populations and the reference
      genome PN40024. Since this is the first application of the Vitis9KSNP array in a
      breeding program, some suggestions are provided for application of genotyping
      arrays. Our results provide novel markers for tracking and pyramiding this unique
      resistance gene and for further functional characterization of this region on
      chromosome 18 encoding multiple disease resistance and seedlessness.

PMID- 21904847
TI  - Treatment of atrial fibrillation in the elderly: time for a change?

PMID- 21904848
TI  - Invasive coronary imaging in animal models of atherosclerosis.

PMID- 21904849
TI  - Characterisation of a highly pathogenic H5N1 clade 2.3.2 influenza virus isolated
      from swans in Shanghai, China.
AB  - In spring 2009, one strain of H5N1 clade 2.3.2 virus was isolated from wild swans
      in Shanghai, indicating the importance of the wild swan in the ecology of this
      highly pathogenic avian influenza virus (HPAIV) in Eastern China. Pathogenicity
      experiments conducted in this study indicated that the virus was highly
      pathogenic for chickens but lowly pathogenic for mammalian hosts, as evidenced by
      reduced infection of mice. The analysis of complete genome sequences and genetic
      evolution showed that A/Swan/Shanghai/10/09 (SW/SH/09) may be derived from the
      strain A/silky chicken/Shantou/475/2004 (CK/ST/04), which is homologous to the
      influenza viruses isolated from chicken, duck, pika, little egret, swan, mandarin
      duck and bar-headed goose in China Hunan, China Qinghai, Mongolia, Russia, Japan,
      Korea, Laos and Hong Kong during 2007-2011, indicating that the virus has retro
      infected diverse wild birds from chicken, and significant spread of the virus is
      still ongoing through overlapping migratory flyways. On the basis of the
      molecular analysis, we also found that there was a deletion of the glycosylation
      site (NSS) in amino acid 156 of the hemagglutinin (HA) protein when compared with
      that of the other Clade 2.3.2 viruses isolated between 2007 and 2011. More
      importantly, the sequence analysis of SW/SH/09 virus displayed the drug-resistant
      mutations on the matrix protein (M2) and neuraminidase (NA) genes.

PMID- 21904853
TI  - TET2, ASXL1, IDH1, IDH2, and c-CBL genes in JAK2- and MPL-negative
      myeloproliferative neoplasms.
AB  - Mutations in the TET2 and ASXL1 genes have been described in approximately 14%
      and 8% of patients, respectively, with classic myeloproliferative neoplasms
      (MPN), but their role as possible new diagnostic molecular markers is still
      inconclusive. In addition, other genes such as IDH1, IDH2, and c-CBL have also
      been reported in several myeloid neoplasms. We have studied the mutational status
      of TET2 (complete coding region), ASXL1 (exon12), IDH1 (R132), IDH2 (R140 and
      R172), and c-CBL (exons 8 and 9) in 62 MPN patients (52 essential thrombocythemia
      (ET), five polycythemia vera (PV), and five primary myelofibrosis (PMF)) negative
      for both JAK2 (V617F and exon 12) and MPL (exon 10) mutations. Pathogenic
      alterations in the TET2 gene were detected in three out 52 ET cases (4.8%). ASXL1
      gene pathogenic mutations were also detected in three cases (two ET and one PMF).
      One ET patient harbored, simultaneously, one TET2 and one ASXL1 mutations.
      Mutations in the TET2 and ASXL1 genes showed no association with the JAK2 46/1
      haplotype. Analysis of a JAK2V617F-positive cohort of 50 ET patients showed no
      mutations in either the TET2 or ASXL1 genes. Regarding IDH1, IDH2, and c-CBL
      genes, no mutations were found in any patient. In conclusion, TET2 and ASXL1
      pathogenic mutations are found in 8% of MPN lacking JAK2 and MPL mutations,
      whereas IDH1, IDH2, and c-CBL mutations are not detected in this subset of
      patients.

PMID- 21904850
TI  - Serum cadmium levels are independently associated with endothelial function in
      hemodialysis patients.
AB  - OBJECTIVE: Hemodialysis (HD) patients are at risk of deficiency of essential
      trace elements and excess of toxic trace elements. The aim of the study was to
      evaluate the relation between the serum levels of some trace elements and heavy
      metals (iron, zinc, manganese, copper, magnesium, cobalt, cadmium, and lead) and
      endothelial function in HD patients. METHODS: Forty-eight chronic HD patients
      without known atherosclerotic disease and 42 age- and sex-matched healthy
      individuals were included in the study. The serum levels of trace elements (iron,
      zinc, manganese, copper, and magnesium) and heavy metals (cobalt, cadmium, and
      lead) were measured by Atomic Adsorption Spectrophotometer (UNICAM-929). RESULTS:
      The serum levels of iron, zinc, and manganese were lower, and levels of copper,
      magnesium, cobalt, cadmium, and lead were higher in HD patients compared to
      controls. Flow-mediated dilatation (FMD %) in HD patients was lower than that in
      the control group (7.27 +/- 0.76 vs. 11.29 +/- 0.82, P < 0.001). There was a
      significant negative correlation between FMD % and serum levels of cobalt (r = 
      0.313, P = 0.03) and cadmium (r = -0.524, P < 0.01). A linear regression analysis
      showed that serum cadmium levels were still significantly and negatively
      correlated with FMD % (regression coefficient = -0.526, P < 0.001). CONCLUSION:
      We first demonstrated that serum cadmium levels independently predict endothelial
      function in HD patients without known atherosclerotic disease.

PMID- 21904855
TI  - Submental lymph node metastasis from invasive ductal breast carcinoma.
AB  - This case report presents a 52-year-old woman with a submental swelling which
      arose 3 years after wide local excision and axillary lymphadenectomy for breast
      carcinoma. Histopathological examination after excision biopsy of this lesion
      confirmed the presence of invasive breast carcinoma in a submental lymph node.
      Computed tomography of the head, neck, thorax, abdomen and pelvis demonstrated
      multiple brain and pulmonary metastases. Further management was palliative and
      the patient died 5 months later. This is the first description of a breast
      carcinoma metastasising to the submental region. Metastatic breast carcinoma
      should be considered in the differential diagnosis of head and neck
      lymphadenopathy in patients with previously diagnosed breast carcinoma.

PMID- 21904854
TI  - Uterine arteriovenous malformations induced after diagnostic curettage: a
      systematic review.
AB  - PURPOSE: To perform an extensive systematic review to examine all the available
      literature reporting iatrogenic acquired arteriovenous malformation (AVM) induced
      after diagnostic curettage and to describe a further case of a 34-year-old woman
      presenting with acute vaginal bleeding due to AVM induced after uterine curettage
      for termination of pregnancy. METHODS: We searched the electronic databases:
      MEDLINE (1950-2011), Embase (1980-2011), Cochrane Library (2004-2011), Cinahl
      (1981-2011), Popline (2004-2011). RESULTS: Initial search extracted 333 relevant
      articles. Final assessment resulted to the inclusion of 91 studies, 85 case
      reports and 6 observational studies. Studies are dated between 1954 and 2011. A
      metanalysis of the 85 case reports reporting 100 patients was performed. The mean
      age of the women diagnosed with AVM was 30 +/- 9.1 years, range (16-72) years, 96
      women were premenopausal (96%) and 4 were postmenopausal (4%). Ultrasound imaging
      was applied in 86 patients (86%), and ultrasound combined with angiography was
      performed in 51 patients (51%). Uterine artery embolization (UAE) was the most
      common treatment option performed in 59 patients (59%). Total abdominal
      hysterectomy was performed in 29 patients (29%). Spontaneous resolution of AVM
      occurred in six patients (6%). In 17 patients (17%), recurrence occurred after
      treatment with UAE. Twenty-four articles reported pregnancies in 27 patients
      (27%). CONCLUSION: Ultrasound imaging with appropriate knowledge of color Doppler
      features minimizes the use of inappropriate interventional procedures such as
      diagnostic curettage. UAE is effective in treatment, and rarely leads to
      complications.

PMID- 21904856
TI  - Biomarker responses in fish exposed to sediments from northern Taihu Lake.
AB  - Our study investigated multiple biomarker responses of goldfish exposed to
      sediments collected from northern Taihu Lake. The activities of
      acetylcholinesterase, 7-ethoxyresorufin-O-deethylase, glutathione-S-transferase
      and superoxide dismutase did not differ significantly from controls following
      exposure to sediment from the center of the lake. However, sediment collected
      from the northern bays did significantly alter enzymatic activities. An
      integrated biomarker response (IBR) was calculated and used to evaluate the
      impact of pollutants from different stations. The results indicated that Mashan
      in Meiliang Bay and Xiaogongshan in Gong Bay were the most stressful places for
      fish. Sediment polychlorinated biphenyl and polybrominated diphenyl ether
      concentrations were associated with IBR variation.

PMID- 21904857
TI  - The effect of a whole-system approach in an antimicrobial stewardship programme
      at the Singapore General Hospital.
AB  - Inappropriate antibiotic use contributes to antimicrobial resistance. Multi
      faceted antimicrobial stewardship programmes (ASPs) are recommended for
      sustainable changes in prescribing practices. A multi-disciplinary ASP was
      established in October 2008 and piloted in the Departments of General Surgery,
      Renal Medicine and Endocrinology sequentially. To improve the quality of patient
      care via optimising the (1) choice, (2) dose, (3) route and (4) duration of
      antibiotics, a "whole-system" approach incorporating prospective review with
      immediate concurrent feedback (ICF), prescriber education (public or
      individualised), de-escalation of therapy, dose optimisation and parenteral-to
      oral conversion, while recognising the autonomy of primary prescribers, was
      adopted. The audited department received a quarterly outcomes report and any
      common unaccepted practices would be addressed. Outcomes were analysed for 12
      months post-ASP implementation. A total of 1,535 antibiotic prescriptions were
      reviewed. Antimicrobial use in 376 (24.5%) prescriptions was inappropriate. Of
      596 interventions made, 70.2% were accepted. A reduction in audited antibiotics
      consumption resulted in acquisition cost savings of S$198,575 for the hospital.
      Patients' cost-savings attributable to ASP-initiated interventions were $91,194.
      The overall all-cause mortality rate and median monthly inpatient-days pre- and
      post-intervention remained stable. A "whole-system" ASP was effective in
      optimising antibiotic use in our hospital, without compromising clinical
      outcomes.

PMID- 21904858
TI  - Utility of the Etest GRD for detecting Staphylococcus aureus with reduced
      susceptibility to glycopeptides in cystic fibrosis patients.
AB  - Glycopeptide-intermediate S. aureus (GISA), particularly heterogeneous GISA
      (hGISA), remain difficult to detect in the routine practice of medical
      microbiology. Novel tools have been evaluated comparatively to the population
      analysis profile-area under the curve (PAP-AUC) reference method for detecting
      GISA/hGISA. Among them, the Etest GRD showed relatively high specificity (85.8
      97%) and negative predictive value (97%) but lower sensibility (57-95%) and
      positive predictive value (30.8%). We investigated the utility of the Etest GRD
      for detecting GISA/hGISA among 180 strains isolated from 106 cystic fibrosis (CF)
      patients. Etest GRD was performed on all isolates, and those exhibiting a
      GISA/hGISA phenotype were further tested by PAP-AUC and other agar routine assays
      for GISA/hGISA detection. The Etest GRD allowed the detection of 15 GISA/hGISA
      strains, of which eight were confirmed by the reference method. Despite the 3.9%
      level of false positive results, the Etest GRD constitutes a useful routine tool
      for detecting GISA/hGISA overlooked by other routine assays, two strains being
      detected by the Etest GRD only. GISA/hGISA represented 7.7% of MRSA and 2.1% of
      MSSA, and were found in 4.7% of CF patients colonized/infected by S. aureus,
      which is the highest rate reported to date in this population.

PMID- 21904859
TI  - Comparison of sterilization of reusable endoscopic biopsy forceps by autoclaving
      and ethylene oxide gas.
AB  - BACKGROUND AND AIMS: Every country has standardized reprocessing guidelines for
      reducing the risk of microorganism transmission via reusable biopsy forceps.
      Sterilization is performed either by autoclaving or with the use of ethylene
      oxide (EO) gas. However, there are no clear standard global recommendations. The
      aim of this study was to determine whether EO gas or autoclaving is a safer and
      more effective method for the sterilization of reusable forceps. METHODS: This
      was a prospective study conducted at multiple tertiary referral centers. Seventy
      reusable biopsy forceps that had been reused at least 20 times each were
      collected from six endoscopy centers. In all, 61 forceps from five centers were
      sterilized using EO gas, and the nine forceps from the remaining center were
      placed in an autoclave. We performed real-time polymerase chain reaction (RT-PCR)
      for Mycobacterium tuberculosis and hepatitis B virus and performed bacterial
      cultures on the reusable forceps, which were cut into 2- to 3-cm sections. The
      forceps were also scanned with an electron microscope (EM) to detect surface
      damage and contamination. RESULTS: Escherichia coli bacteria were cultured from 2
      of the 61 (3.3%) reusable biopsy forceps sterilized with EO gas. On EM scanning,
      abundant debris and tissue materials remained on the cup surfaces of the reused
      biopsy forceps and on their inner wires. No microorganisms were found on the
      autoclaved forceps. CONCLUSIONS: Sterilization with EO gas may be inadequate
      because the complicated structure of the forceps may interfere with
      sterilization. Therefore, for optimum safety, reusable biopsy forceps should be
      sterilized by autoclaving.

PMID- 21904860
TI  - Preventing young children's injuries: analysis of data from a population-based
      surveillance.
AB  - The objective of this study is to determine prevention strategies for potentially
      serious injury events among children younger than 3 years of age based upon
      circumstances surrounding injury events. Surveillance was conducted on all
      injuries to District of Columbia (DC) residents less than 3 years old that
      resulted in an Emergency Department (ED) visit, hospitalization, or death for 1
      year. Data were collected through abstraction of medical records and interviews
      with a subset of parents of injured children. Investigators coded injury-related
      events for the potential for death or disability. Potential prevention strategies
      were then determined for all injury events that had at least a moderate potential
      for death or disability and sufficient detail for coding (n = 425). Injury
      related events included 10 deaths, 163 hospitalizations, and 2,868 ED visits
      (3,041 events in total). Of the hospitalizations, 88% were coded as moderate or
      high potential for disability or death, versus only 21% of the coded ED visits.
      For potentially serious events, environmental change strategies were identified
      for 47%, behavior change strategies for 77%, and policy change strategies for
      24%. For 46% of the events more than one type of prevention strategy was
      identified. Only 8% had no identifiable prevention strategy. Prevention
      strategies varied by specific cause of injury. Potential prevention strategies
      were identifiable for nearly all potentially serious injury events, with multiple
      potential prevention strategies identified for a large fraction of the events.
      These findings support developing multifaceted prevention approaches informed by
      community-based injury surveillance.

PMID- 21904861
TI  - Epidemiology and cost of ventral hernia repair: making the case for hernia
      research.
AB  - PURPOSE: Ventral hernia repair (VHR) lacks standardization of care and exhibits
      variation in delivery. Complications of VHR, notably recurrence and infection,
      increase costs. Efforts at obtaining federal funding for VHR research are
      frequently unsuccessful, in part due to misperceptions that VHR is not a clinical
      challenge and has minimal impact on healthcare resources. We analyzed national
      trends for VHR performance and associated costs to demonstrate potential savings
      resulting from an improvement in outcomes. METHODS: Inpatient non-federal
      discharges for VHR were identified from the 2001-2006 Healthcare Cost and
      Utilization Project, supplemented by the Center for Disease Control 2006 National
      Survey of Ambulatory Surgery for outpatient estimates. The total number of VHRs
      performed in the US was estimated along with associated costs. Costs were
      standardized to 2010 US dollars using the Consumer Price Index and reported as
      mean with 95% confidence intervals (95% CI). RESULTS: The number of inpatient
      VHRs increased from 126,548 in 2001 to 154,278 in 2006. Including 193,543
      outpatient operations, an estimated 348,000 VHRs were performed for 2006.
      Inpatient costs consistently rose with 2006 costs estimated at US $15,899 (95% CI
      $15,394-$16,404) per operation. Estimated cost for outpatient VHR was US $3,873
      (95% CI $2,788-$4,958). The total cost of VHR for 2006 was US $3.2 billion.
      CONCLUSIONS: VHRs continue to rise in incidence and cost. By reducing recurrence
      rate alone, a cost saving of US $32 million dollars for each 1% reduction in
      operations would result. Further research is necessary for improved understanding
      of ventral hernia etiology and treatment and is critical to cost effective
      healthcare.

PMID- 21904862
TI  - Unreported location and presentation for a parasitic ovarian dermoid cyst in an
      indirect inguinal hernia.
AB  - Extragonadal mature cystic teratomas (dermoid cysts) have been reported
      occasionally, with the most common site being the omentum. We report a rare case
      of a parasitic dermoid cyst that was incidentally found in an indirect inguinal
      hernia sac in a 66-year-old woman. The right ovary was absent from its proper
      anatomical location. Histopathologic study revealed a mature cystic teratoma with
      viable ovarian tissue. These findings suggested auto-amputation of the ovary
      either by inflammation or torsion.

PMID- 21904863
TI  - Organochlorine compounds in red deer (Cervus elaphus L.) and fallow deer (Dama
      dama L.) from inland and coastal Croatia.
AB  - Polychlorinated biphenyl (PCB) and organochlorine pesticide (OCP) levels in fat
      tissue of red and fallow deer (Cervus elaphus L. and Dama dama L.) from two
      inland and an Adriatic area were established. Of 17 analysed PCBs, PCB-28, PCB
      138, PCB-153, PCB-180 and PCB-118 were found in all samples, whilst PCB-101 and
      PCB-170 were found in more than 50% of samples. They ranged between 0.03 and 5.98
      ng g(-1) fat weight. Of seven analysed OCPs, HCB, gamma-HCH and 1,1-dichloro-2,2
      di(4-chlorophenyl)ethylene (DDE) were found in all samples, whilst beta-HCH was
      found in more than 50% of samples. They ranged between 0.17 and 22.14 ng g(-1)
      fat weight. The dominating compounds were DDE, PCB-138, PCB153, PCB-118 and PCB
      180. According to the Duncan multistage test, the levels of PCB-138, PCB-153, PCB
      170 and PCB-180 were significantly higher in perirenal fat samples of specimens
      taken from the Adriatic area. DDE was significantly higher in the inland deer
      samples. Some species differences were determined and were mostly related to
      higher PCB and beta-HCH levels in fallow deer samples and higher DDE levels in
      red deer samples. No sex difference was established. As for age, significantly
      higher levels of PCB-118 and PCB-52 were found in fawns.

PMID- 21904864
TI  - Spontaneous intracranial extradural haematoma associated with frontal sinusitis
      and orbital involvement.
AB  - Intracranial extradural hematoma is usually traumatic. Rarely, it can occur
      spontaneously associated with coagulative disorders (spontaneous or iatrogenic),
      dural vascular malformation, cranio-facial tumors and infections. In these cases,
      spontaneous extradural hematoma (SEH) is a serious event that needs to be
      recognized and managed in time to avoid fatal outcome. The authors report a case
      of a 12-year-old young girl with a 3-year history of right frontal sinusitis
      treated urgently for a right frontal extradural hematoma involving the orbit.
      Diagnosis and management of this case is discussed reviewing the pertinent
      literature.

PMID- 21904865
TI  - Cough headache secondary to spontaneous intracranial hypotension complicated by
      cerebral venous thrombosis.
AB  - Cough headache may be the clinical manifestation, sometimes isolated, of an
      intracranial disease. There are several possible causes of secondary cough
      headache. The hypothesis that cough headache may be the expression of spontaneous
      intracranial hypotension has been advanced only recently. In fact, this would
      represent an exception to the rule that cough headache is generally secondary to
      conditions leading to an increase in intracranial pressure and/or volume. We
      report and discuss a case of cough headache secondary to spontaneous intracranial
      hypotension in an otherwise healthy 59-year-old man. The condition was
      complicated by cerebral venous thrombosis.

PMID- 21904866
TI  - Comparative fibril formation of analogs corresponding to the (12-24) segment of
      the beta-amyloid peptide.
AB  - The (1-42) beta-amyloid peptide is a main component of the plaques found in the
      brain of patients suffering from the Alzheimer's disease. As the single
      substitution of Glu for Gln at position 22 of this peptide seems to be
      responsible for the manifestation of the more severe amyloidosis (Dutch-type), we
      decided to evaluate the aggregation characteristics of peptide analogs
      interchanging Glu and Gln residues at positions 22 and also 15 in the minor (12
      24) (VHHQ(15)KLVFFAE(22)DV) fragment. The Q15Q22, E15E22, E15Q22 and the native
      Q15E22 were compared to the (1-42) beta-amyloid peptide in terms of fibril or
      structured aggregates formation propensity. In contrast to a rather similar
      solubility data measured of all analogs, fluorescence and light scattering
      methods indicated that only Q15E22 and Q15Q22 displayed relevant fibril formation
      capacity. Conversely, E15E22 and E15Q22 were not capable of the formation of this
      type of structure thus suggesting a key role for the Q(15) residue in the unique
      aggregation characteristic of the beta-amyloid peptide.

PMID- 21904867
TI  - The effects of aging and Alzheimer's disease on associative recognition memory.
AB  - We investigated the effects of aging and Alzheimer's disease (AD) on item and
      associative recognition memory. Three groups of participants (younger adults,
      elderly adults, and AD patients) studied photographs of common objects that were
      located on either the left or the right side of a black computer screen inside
      either a red or a blue square. In a subsequent old/new recognition memory test,
      the participants were presented with four kinds of stimuli: "intact" stimuli,
      which were presented as they were during the study phase; "location-altered"
      stimuli, which were presented in a different location; "color-altered" stimuli,
      which were presented with a different surrounding color; and "new" stimuli, which
      consisted of photographs that had not been presented during the study phase.
      Compared with younger adults, the older adults showed equivalent performance in
      simple item recognition but worse performance in discriminating location-altered
      and color-altered stimuli. Compared with older adults, the AD patients showed
      equivalent performance in discriminating color-altered stimuli but worse
      performance in simple item recognition and the discrimination of location-altered
      stimuli. We speculate that distinct structural and functional changes in specific
      brain regions that are caused by aging and AD are responsible for the different
      patterns of memory impairment.

PMID- 21904868
TI  - Selection and constraint on regulatory elements in Drosophila simulans.
AB  - We utilized available Drosophila simulans molecular population genomic data to
      characterize sequence polymorphism in noncoding regulatory regions and their
      corresponding transcribed target genes or interacting transcription factors. We
      highlight two properties of regulatory evolution. First, we find that sequence
      divergence between D. melanogaster and D. simulans is greater at regulatory sites
      than expected from levels of intraspecific polymorphism, suggestive of positive
      selection. Second, we compared variation in cis-regulatory regions to that of the
      transcription factors and transcribed target genes with which they are
      associated. We find a correlation in polymorphism between cis-regulatory regions
      and the transcription factors which they bind, but not between cis-regulatory
      regions and the physically neighboring target genes which they directly regulate.
      This result indicates that the evolution of cis-regulatory elements is
      constrained by the interactions among transcription factors and regulatory
      regions. More broadly, these findings support the general importance of noncoding
      regulatory DNA in evolution.

PMID- 21904869
TI  - The demographic, system, and psychosocial origins of mammographic screening
      disparities: prediction of initiation versus maintenance screening among
      immigrant and non-immigrant women.
AB  - Disparities in breast screening are well documented. Less clear are differences
      within groups of immigrant and non-immigrant minority women or differences in
      adherence to mammography guidelines over time. A sample of 1,364 immigrant and
      non-immigrant women (African American, English Caribbean, Haitian, Dominican,
      Eastern European, and European American) were recruited using a stratified
      cluster-sampling plan. In addition to measuring established predictors of
      screening, women reported mammography frequency in the last 10 years and were
      (per ACS guidelines at the time) categorized as never, sub-optimal (<1
      screen/year), or adherent (1+ screens/year) screeners. Multinomial logistic
      regression showed that while ethnicity infrequently predicted the never versus
      sub-optimal comparison, English Caribbean, Haitian, and Eastern European women
      were less likely to screen systematically over time. Demographics did not predict
      the never versus sub-optimal distinction; only regular physician, annual exam,
      physician recommendation, and cancer worry showed effects. However, the adherent
      categorization was predicted by demographics, was less likely among women without
      insurance, a regular physician, or an annual exam, and more likely among women
      reporting certain patterns of emotion (low embarrassment and greater worry).
      Because regular screening is crucial to breast health, there is a clear need to
      consider patterns of screening among immigrant and non-immigrant women as well as
      whether the variables predicting the initiation of screening are distinct from
      those predicting systematic screening over time.

PMID- 21904870
TI  - Solution NMR structure of Dsy0195 homodimer from Desulfitobacterium hafniense:
      first structure representative of the YabP domain family of proteins involved in
      spore coat assembly.
AB  - Protein domain family YabP (PF07873) is a family of small protein domains that
      are conserved in a wide range of bacteria and involved in spore coat assembly
      during the process of sporulation. The 62-residue fragment of Dsy0195 from
      Desulfitobacterium hafniense, which belongs to the YabP family, exists as a
      homodimer in solution under the conditions used for structure determination using
      NMR spectroscopy. The structure of the Dsy0195 homodimer contains two identical
      62-residue monomeric subunits, each consisting of five anti-parallel beta strands
      (beta1, 23-29; beta2, 31-38; beta3, 41-46; beta4, 49-59; beta5, 69-80). The
      tertiary structure of the Dsy0195 monomer adopts a cylindrical fold composed of
      two beta sheets. The two monomer subunits fold into a homodimer about a single C2
      symmetry axis, with the interface composed of two anti-parallel beta strands,
      beta1-beta1' and beta5b-beta5b', where beta5b refers to the C-terminal half of
      the bent beta5 strand, without any domain swapping. Potential functional regions
      of the Dsy0195 structure were predicted based on conserved sequence analysis. The
      Dsy0195 structure reported here is the first representative structure from the
      YabP family.

PMID- 21904871
TI  - Important photosynthetic contribution from the non-foliar green organs in cotton
      at the late growth stage.
AB  - Non-foliar green organs are recognized as important carbon sources after leaves.
      However, the contribution of each organ to total yield has not been
      comprehensively studied in relation to the time-course of changes in surface area
      and photosynthetic activity of different organs at different growth stages. We
      studied the contribution of leaves, main stem, bracts and capsule wall in cotton
      by measuring their time-course of surface area development, O(2) evolution
      capacity and photosynthetic enzyme activity. Because of the early senescence of
      leaves, non-foliar organs increased their surface area up to 38.2% of total at
      late growth stage. Bracts and capsule wall showed less ontogenetic decrease in
      O(2) evolution capacity per area and photosynthetic enzyme activity than leaves
      at the late growth stage. The total capacity for O(2) evolution of stalks and
      bolls (bracts plus capsule wall) was 12.7 and 23.7% (total ca. 36.4%),
      respectively, as estimated by multiplying their surface area by their O(2)
      evolution capacity per area. We also kept the bolls (from 15 days after anthesis)
      or main stem (at the early full bolling stage) in darkness for comparison with
      non-darkened controls. Darkening the bolls and main stem reduced the boll weight
      by 24.1 and 9%, respectively, and the seed weight by 35.9 and 16.3%,
      respectively. We conclude that non-foliar organs significantly contribute to the
      yield at the late growth stage.

PMID- 21904872
TI  - AtPTR4 and AtPTR6 are differentially expressed, tonoplast-localized members of
      the peptide transporter/nitrate transporter 1 (PTR/NRT1) family.
AB  - Members of the peptide transporter/nitrate transporter 1 (PTR/NRT1) family in
      plants transport a variety of substrates like nitrate, di- and tripepetides,
      auxin and carboxylates. We isolated two members of this family from Arabidopsis,
      AtPTR4 and AtPTR6, which are highly homologous to the characterized di- and
      tripeptide transporters AtPTR1, AtPTR2 and AtPTR5. All known substrates of
      members of the PTR/NRT1 family were tested using heterologous expression in
      Saccharomyces cerevisiae mutants and oocytes of Xenopus laevis, but none could be
      identified as substrate of AtPTR4 or AtPTR6. AtPTR4 and AtPTR6 show distinct
      expression patterns, while AtPTR4 is expressed in the vasculature of the plants,
      AtPTR6 is highly expressed in pollen and during senescence. Phylogenetic analyses
      revealed that AtPTR2, 4 and 6 belong to one clade of subgoup II, whereas AtPTR1
      and 5 are found in a second clade. Like AtPTR2, AtPTR4-GFP and AtPTR6-GFP fusion
      proteins are localized at the tonoplast. Vacuolar localization was corroborated
      by co-localization of AtPTR2-YFP with the tonoplast marker protein GFP-AtTIP2;1
      and AtTIP1;1-GFP. This indicates that the two clades reflect different
      intracellular localization at the tonoplast (AtPTR2, 4, 6) and plasma membrane
      (AtPTR1, 5), respectively.

PMID- 21904874
TI  - Comparative development of heavily asymmetric-cordate gametophytes of Anemia
      phyllitidis (Anemiaceae) focusing on meristem behavior.
AB  - Development of heavily asymmetric cordate gametophytes of Anemia phyllitidis
      (Anemiaceae), one of the schizaeoid ferns, was examined using a sequential
      observation technique; epi-illuminated light micrographs of the same growing
      gametophytes were taken approximately every 24 h. The apical cell-like wedge
      shaped cell was produced once from the terminal cell of a germ filament, but it
      stopped dividing soon after production of one or two derivative cells. Without a
      functional apical cell, the gametophyte developed by intercalary growth until the
      early stage of wing formation, and then the multicellular (pluricellular)
      meristem arose from the lower lateral side of the gametophyte. This was in sharp
      contrast to the observation that the multicellular meristem forms in place of the
      apical cell in typical cordate gametophytes. Loss of the functional apical cell
      probably caused a site-shift in the multicellular meristem of the Anemia
      phyllitidis gametophyte during evolution from apical to lateral. The results
      suggest that apical cell-based and multicellular meristems are primarily
      independent of each other. The multicellular meristem produced cells equally in
      the distal and proximal directions to form wings in both directions but
      proximally produced cells divided much less frequently. As a result, a heavily
      asymmetric gametophyte was formed.

PMID- 21904873
TI  - Association of tumor necrosis factor-alpha (TNF-alpha) promoter polymorphisms
      with overweight/obesity in a Korean population.
AB  - OBJECTIVE: Obesity is characterized by the activation of an inflammatory process
      leading to an increase in proinflammatory cytokines and adipokines. This study
      was designed to investigate the genetic association between tumor necrosis factor
      alpha (TNF-alpha) polymorphisms and the risk of obesity in the Korean population.
      METHODS: Three single nucleotide polymorphisms [G-238A (rs361525), C-857T
      (rs1799724), and C-863A (rs1800630)] in the promoter region of TNF-alpha gene
      were analyzed in 123 control [body mass index (BMI) between 18 and 23] and 208
      overweight/obese (BMI >= 23) subjects. RESULTS: The mean values of BMI in the
      control and overweight/obese groups were 21.1 +/- 1.4 and 25.4 +/- 1.8,
      respectively. Of the three SNPs, G-238A presented a significant association with
      overweight/obesity in the codominant model; the frequency of the G/G genotype in
      the overweight/obese group was 9.3% higher than that in the control group (P =
      0.0046). When control and overweight/obesity subjects were combined together and
      analyzed, the level of high-density lipoprotein (HDL) was significantly higher in
      the C-857T C/C type SNP (P < 0.05). CONCLUSIONS: The results of this study
      suggest that the G allele of G-238A in TNF-alpha gene may be a risk factor for
      overweight/obesity in the Korean population and that the C allele of C-857T may
      be an protective factor in relation to the HDL level in the general Korean
      population.

PMID- 21904875
TI  - Comparison of wood-inhabiting myxomycetes in subalpine and montane coniferous
      forests in the Yatsugatake Mountains of Central Japan.
AB  - To demonstrate altitudinal gradients (and resulting temperatures) that affect
      myxomycete biodiversity and species composition, we statistically compared
      myxomycete assemblages between a subalpine coniferous forest and a montane pine
      forest within the region of the Yatsugatake Mountains, Nagano Prefecture, Central
      Japan. In summer and autumn field surveys during 2003-2010, 53 myxomycete taxa
      (with varieties treated as species) were observed from 639 records of fruiting
      bodies in the subalpine forest and 32 taxa were detected from 613 records in the
      montane forest. There were 20 species in common between the assemblages and the
      percentage similarity index was 0.400. Myxomycete biodiversity was higher in the
      subalpine than in the montane forest. Nine myxomycete species were statistically
      frequent occurrences in the subalpine forest and appeared in autumn: Lamproderma
      columbinum, Cribraria macrocarpa, Trichia botrytis, Physarum newtonii, Diderma
      ochraceum, Enteridium splendens, Elaeomyxa cerifera, Trichia verrucosa, and
      Colloderma oculatum. Five species were restricted to appear in the subalpine
      forest: Cribraria purpurea, Cribraria rufa, Cribraria ferruginea, Cribraria
      piriformis, and Lepidoderma tigrinum. Dead wood in the subalpine forest provided
      a breeding habitat for specific myxomycetes that inhabit cold areas; that is
      those areas having geographical features of decreasing temperature and increasing
      elevation, such as the temperate area of Central Japan.

PMID- 21904876
TI  - Floral structure of Cardiopteris (Cardiopteridaceae) with special emphasis on the
      gynoecium: systematic and evolutionary implications.
AB  - Cardiopteris, a small herbaceous genus, had long been placed in its own family,
      Cardiopteridaceae. However, the family was recently broadly circumscribed to
      include more genera in Aquifoliales. To better understand the morphological
      relationships of the genus and the family, I studied the floral anatomy and
      development of Cardiopteris using C. quinqueloba. As has been previously
      described, flowers are 5-merous with a unilocular gynoecium. I confirmed that the
      gynoecium is bicarpellate, possessing two dissimilar styles. An analysis of the
      development, structure, and vasculature of the gynoecium showed that it is
      pseudomonomerous, consisting of one fertile adaxial carpel and one solid sterile
      abaxial carpel. The adaxial carpel forms a thin style with a capitate stigma,
      whereas the abaxial carpel has a thick style, which develops into a freshy fruit
      appendage. Comparisons with flowers of other genera (Citronella, Gonocaryum, and
      Leptaulus) of Cardiopteridaceae as well as the other families (Aquifoliaceae,
      Helwingiaceae, Phyllonomaceae, and Stemonuraceae) of Aquifoliales showed that the
      pseudomonomerous gynoecium is very likely a synapomorphy to support the sister
      group relationship between Cardiopteridaceae and Stemonuraceae. Moreover,
      contrary to all previous descriptions, Cardiopteris flowers were found to have an
      annular nectariferous disk at the base of the gynoecium.

PMID- 21904878
TI  - Insulin contributes to fine-tuning of the pancreatic beta-cell response to
      glucagon-like peptide-1.
AB  - Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion from pancreatic beta
      cells in a glucose-dependent manner. However, factors other than glucose that
      regulate the beta-cell response to GLP-1 remain poorly understood. In this study,
      we examined the possible involvement of insulin and receptor tyrosine kinase
      signaling in regulation of the GLP-1 responsiveness of beta-cells. Pretreatment
      of beta-cells with HNMPA, an insulin receptor inhibitor, and AG1478, an epidermal
      growth factor receptor inhibitor, further increased the cAMP level and Erk
      phosphorylation in the presence of exendin-4 (exe-4), a GLP-1 agonist. When beta
      cells were exposed to a high concentration of glucose (25 mM), which stimulates
      insulin secretion, exe-4-induced cAMP formation declined gradually as exposure
      time was increased. This decreased cAMP formation was not observed in the
      presence of HNMPA. HNMPA was able to further increase the exe-4-induced insulin
      secretion when beta-cells were exposed to high glucose for 18 h. Treatment of
      beta-cells with insulin significantly decreased exe-4-induced cAMP formation in a
      dose-dependent manner. Lowering the phospho-Akt level by HNMPA or LY294002, a
      PI3K inhibitor, further augmented exe-4-induced cAMP formation and Erk
      phosphorylation. These results suggest that insulin contributes to fine-tuning of
      the beta-cell response to GLP-1.

PMID- 21904880
TI  - Peptidoglycan from Staphylococcus aureus increases MUC5AC gene expression via
      RSK1-CREB pathway in human airway epithelial cells.
AB  - Respiratory tract exposure to viruses, air pollutants, or bacterial pathogens can
      lead to pulmonary diseases. The molecular mechanism of mucous overproduction
      increased by these pathogens provides the knowledge for developing new
      therapeutic strategies. There is established in vitro data demonstrating that the
      overexpression of MUC5AC is induced by peptidoglycan (PGN) derived from
      Staphylococcus aureus. However, the mechanisms by which PGN activates MUC5AC gene
      expression in the airway remain unclear. The aim of this study was to identify
      the mechanism of PGN-induced MUC5AC gene expression. We found that PGN could
      induce MUC5AC gene expressions in a time- and dose-dependent manner. Moreover,
      activations of ERK1/2 and JNK increased after treatment of cells with PGN,
      whereas phosporylation of p38 was undetected. Of these MAPKs, pharmacologic
      inhibition of ERK1/2 decreased PGN-induced MUC5AC gene expression. In addition,
      we checked the activation of p90 ribosomal S6 kinase 1 (RSK1) as a downstream
      signaling target of ERK1/2 in PGN signaling. The activation of RSK1 was prevented
      by pretreatment with PD98059. We also found that RSK1 mediated the PGN-induced
      phosphorylation of cAMP response element-binding protein (CREB) and the
      transcription of MUC5AC. Furthermore, the cAMP-response element (CRE) in the
      MUC5AC promoter appears to be important for PGN-induced MUC5AC gene expression in
      NCI-H292 cells.

PMID- 21904879
TI  - Tcf3 function is required for the inhibition of oligodendroglial fate
      specification in the spinal cord of zebrafish embryos.
AB  - The generation of various subtypes of neurons and glial cells at the right time
      and place is crucial for the proper development of the vertebrate CNS. Although
      the mechanisms and factors for the regulation of neuronal diversity in the CNS
      have been well studied, the mechanisms regulating the sequential production of
      neuronal and glial cells from neural precursors remain poorly understood. This
      study shows that Tcf3, a member of the Lef/Tcf family of proteins, is required to
      inhibit the premature oligodendroglial fate specification of spinal cord
      precursors using the transgenic zebrafish, which expresses a dominant repressor
      form of Tcf3 under the control of a heat-shock inducible promoter. In addition,
      the data revealed that Tcf3 function in oligodendroglial fate specification is
      mediated independently of canonical Wnt signaling. Altogether, these results show
      a novel function for Tcf3 in regulating the timing of oligodendroglial fate
      specification in the spinal cord.

PMID- 21904881
TI  - Negative regulation of pathogenesis in Pseudomonas syringae pv. tabaci 11528 by
      ATP-dependent Lon protease.
AB  - Pseudomonas syringae pv. tabaci causes wildfire disease in tobacco plants. The
      hrp pathogenicity island (hrp PAI) of P. syringae pv. tabaci encodes a type III
      secretion system (TTSS) and its regulatory system, which are required for
      pathogenesis in plants. Three important regulatory proteins-HrpR, HrpS, and HrpL
      have been identified to activate hrp PAI gene expression. The bacterial Lon
      protease regulates the expression of various genes. To investigate the regulatory
      mechanism of the Lon protease in P. syringae pv. tabaci 11528, we cloned the lon
      gene, and then a Deltalon mutant was generated by allelic exchange. lon mutants
      showed increased UV sensitivity, which is a typical feature of such mutants. The
      Deltalon mutant produced higher levels of tabtoxin than the wild-type. The lacZ
      gene was fused with hrpA promoter and activity of beta-galactosidase was measured
      in hrp-repressing and hrp-inducing media. The Lon protease functioned as a
      negative regulator of hrp PAI under hrp-repressing conditions. We found that
      strains with lon disruption elicited the host defense system more rapidly and
      strongly than the wild-type strain, suggesting that the Lon protease is essential
      for systemic pathogenesis.

PMID- 21904882
TI  - Milk yield estimation of Ogaden cattle breed based on methods of weigh-suckle
      weigh and calves' growth.
AB  - Daily milk yield of Ogaden cattle was estimated from milk suckled by 269 calves
      born and maintained between 1994 and 2004 at Haramaya University Beef Farm,
      Ethiopia. The weigh-suckle-weigh method and the growth of calves were used to
      estimate the yield. Mean predicted daily milk yield of the breed based on the
      weigh-suckle-weigh method was 4.39 +/- 0.03 kg day(-1). Daily milk yield
      estimated from the growth of calves up to 3 months of age was 4.59 +/- 1.43 kg
      day(-1). The milk yield was significantly affected by seasons of calving (p <
      0.001), parities of the dams (p < 0.05), weeks of lactation (p < 0.001) and birth
      weights of calves (p < 0.05). A relatively higher milk yield was observed from
      cows calved during the long rain season. A higher milk yield was produced by cows
      in fifth parity. Heavier calves at birth suckled more milk than lighter calves.
      Daily milk yield was significantly higher in 3-6 weeks of lactation. The result
      of this study indicated that the milk yield produced by Ogaden breed was
      relatively higher than the yield of some Zebu breed measured by partial suckling
      system in Ethiopia and was comparable to the yield from Zebu cattle in the
      tropics estimated by the same method.

PMID- 21904883
TI  - A prospective study of aromatase inhibitor therapy, vitamin D, C-reactive protein
      and musculoskeletal symptoms.
AB  - This study compared type, severity and location of musculoskeletal symptoms and
      associations with 25-hydroxyvitamin D (25(OH)D) and C-reactive protein (CRP)
      concentrations between women initiating aromatase inhibitor (AI) therapy and an
      unexposed comparison group. A 6-month prospective cohort study was conducted,
      enrolling 100 breast cancer patients prior to initiating AI treatment and an
      unexposed comparison group of 200 postmenopausal women. Multivariate associations
      were assessed with generalized linear models. At baseline, 55% of breast cancer
      patients and 63% of the comparison group reported any musculoskeletal symptoms.
      Among the unexposed group, prevalence and severity of symptoms remained constant
      with no statistically significant change over 6 months. Among breast cancer
      patients, but not unexposed women, the pain severity score significantly
      increased over the 6 month period for joint (P (trend) < 0.001), muscle (P
      (trend) = 0.004), and bone pain (P (trend) = 0.01). Women treated with AIs were
      more likely to report pain in wrists/palms (63% at 6 months) compared to
      unexposed women (31% at 6 months) (P < 0.001). 25(OH)D concentrations increased
      over the study period among breast cancer patients (P (trend) = 0.004). An
      increase in pain severity and prevalence was observed among breast cancer
      patients despite an increase in 25 (OH)D concentration. CRP concentrations were
      not associated with symptoms. Musculoskeletal symptoms are common among
      postmenopausal women. Breast cancer patients initiating AI treatment were at
      increased risk for developing new onset and more severe joint, muscle and bone
      pain compared to unexposed women, with a distinct distribution. AI-associated
      symptoms were not associated with 25(OH)D or CRP concentrations.

PMID- 21904884
TI  - Interventions for sexual problems following treatment for breast cancer: a
      systematic review.
AB  - Sexual functioning is an important element of quality of life. Many women
      experience sexual problems as a result of a breast cancer diagnosis and its
      treatment. Little is known about the availability and the effectiveness of
      interventions for sexual problems in this patient population. Six electronic
      databases were searched using Medical Subject Headings and keywords. Additional
      hand searching of the references of relevant papers was also conducted. The
      searches were conducted between October 2010 and January 2011. Papers were
      included if they evaluated interventions for sexual problems caused as a result
      of breast cancer or its treatment. Studies were only included if sexual
      functioning was reported using a patient-reported outcome questionnaire. Studies
      were excluded if sexual functioning was measured but improving sexual problems
      was not one of the main aims of the intervention. 3514 papers were identified in
      the initial search. 21 papers were selected for inclusion. Studies were of mixed
      methodological quality; 15 randomised trials were identified, many included small
      sample sizes and the use of non-validated questionnaires. Three main types of
      interventions were identified: Exercise (2), medical (2) and psycho-educational
      (17). The psycho-educational interventions included skills-based training such as
      problem-solving and communication skills, counselling, hypnosis, education and
      specific sex-therapies. Interventions were delivered to individual patients,
      patients and their partners (couple-based) and groups of patients. The widespread
      methodological variability hinders the development of a coherent picture about
      which interventions work for whom. Tentative findings suggest the most effective
      interventions are couple-based psycho-educational interventions that include an
      element of sexual therapy. More methodologically strong research is needed before
      any intervention can be recommended for clinical practice. Improved screening and
      classification of sexual problems will ensure interventions can be more
      effectively targeted to suit individual patient needs.

PMID- 21904886
TI  - Preventing surgical-site infections after colorectal surgery.
AB  - Surgical-site infection (SSI) is a major contributor to patient mortality rates
      and health care costs. Due to the high risk of bacterial contamination,
      colorectal surgery is associated with a particularly high risk of postoperative
      infection. The surveillance reported here was conducted at Aichi Medical
      University Hospital on 304 patients who underwent elective colorectal resection-
      total or partial--from June 2006 to May 2009. To determine risk factors for SSI,
      multivariate analysis was used. Forty-six (15.1%) patients were diagnosed with
      SSI. Patients who received cefotiam for prophylaxis showed the highest incidence
      of SSI (26.6%), and patients who were administered flomoxef showed the lowest
      incidence (8.1%). Patients who developed SSI were more likely to intraoperative
      blood loss (308.1 +/- 29.8 vs. 153.9 +/- 12.2; p < 0.05), longer postoperative
      antimicrobial administration (5.3 +/- 2.2 vs. 4.5 +/- 1.5; p < 0.05), and longer
      operative time (3.3 +/- 1.6 vs. 2.7 +/- 1.2; p < 0.05). Intraoperative bleeding,
      antimicrobial choices to cover both anaerobic and aerobic bacteria, and length of
      antimicrobial administration were independently predictive of SSI development
      according to multivariate logistic regression analysis. These results suggest
      that the degree of operative invasion and anaerobic bacteria contribute to SSI
      following colorectal surgery.

PMID- 21904885
TI  - Vasculitides throughout history and their clinical treatment today.
AB  - Therapeutic management of the vasculitides is closely linked to modern
      rheumatologic advances, particularly as it relates to the discovery and first
      clinical use of glucocorticoids. These compounds were introduced in the late
      1940s for the treatment of rheumatoid arthritis, but soon after, clinicians in
      Europe and the United States realized that they could have a significant positive
      impact in systemic vasculitides. However, once it was realized that
      glucocorticoid use was associated with a high degree of morbidity, the search for
      better immunosuppressive agents with similar efficacy but improved safety
      profiles was on. During the past several years, several agents have been utilized
      for the therapeutic management of systemic vasculitides, and the list keeps
      growing with the development of newer compounds that have retained efficacy but
      with a better safety profile.

PMID- 21904887
TI  - Prediction of the therapeutic effects of anticoagulation for recent portal vein
      thrombosis: a novel approach with contrast-enhanced ultrasound.
AB  - OBJECTIVE: To examine whether intra-thrombus enhancement on contrast-enhanced
      sonograms can predict the recanalization by anticoagulation for recent portal
      thrombosis. METHODS: This prospective study included 10 patients with a recent
      portal thrombosis and 20 controls (10 cirrhosis patients and 10 healthy subjects,
      all without thrombosis). The diagnosis of thrombosis was based on clinical and
      ultrasound findings. Pre-anticoagulation intra-thrombus enhancement on the
      contrast-enhanced sonogram was examined with respect to the post-anticoagulation
      results or portal enhancement in controls. RESULTS: Complete recanalization was
      obtained in 4 patients with positive intra-thrombus enhancement. However, in 4
      other patients who had a thrombosis showing positive enhancement concurrent with
      one showing negative enhancement, anticoagulation recanalized the former and
      failed to recanalize the latter. Mean onset time of contrast enhancement measured
      from the beginning of hepatic arterial enhancement was significantly longer in
      the thrombus (6.6 +/- 4.3 s, 3-16 s) than in the portal vein of controls
      (cirrhosis, 4.3 +/- 1.4 s, 2-8 s, P = 0.0035; healthy subjects, 2.4 +/- 0.6 s, 1
      3 s, P < 0.0001). Anticoagulation failed to achieve recanalization in 2 patients
      with negative intra-thrombus enhancement. Sensitivity and specificity of contrast
      enhancement for the prediction of post-treatment recanalization was 100%.
      CONCLUSIONS: Intra-thrombus positive enhancement demonstrated on contrast
      enhanced sonograms has promise as a successful predictor of recanalization for
      the recent portal thrombosis.

PMID- 21904888
TI  - Comparison of SSRs and SNPs in assessment of genetic relatedness in maize.
AB  - Advances in high-throughput SNP genotyping and genome sequencing technologies
      have enabled genome-wide association mapping in dissecting the genetic basis of
      complex quantitative traits. In this study, 82 SSRs and 884 SNPs with minor
      allele frequencies (MAF) over 0.20 were used to compare their ability to assess
      population structure, principal component analysis (PCA) and relative kinship in
      a maize association panel consisting of 154 inbred lines. Compared to SNPs, SSRs
      provided more information on genetic diversity. The expected heterozygosity (He)
      of SSRs and SNPs averaged 0.65 and 0.44, and the polymorphic information content
      of these two markers was 0.61 and 0.34 in this panel, respectively. Additionally,
      SSRs performed better at clustering all lines into groups using STRUCTURE and PCA
      approaches, and estimating relative kinship. For both marker systems, the same
      clusters were observed based on PCA and the first two eigenvectors accounted for
      similar percentage of genetic variations in this panel. The correlation
      coefficients of each eigenvector from SSRs and SNPs decreased sharply when the
      eigenvector varied from 1 to 3, but kept around 0 when the eigenvector were over
      3. The kinship estimates based on SSRs and SNPs were moderately correlated (r (2)
      = 0.69). All these results suggest that SSR markers with moderate density are
      more informative than SNPs for assessing genetic relatedness in maize association
      mapping panels.

PMID- 21904889
TI  - n-Butyl isocyanide oxidation at the [NiFe4S4OH(x)] cluster of CO dehydrogenase.
AB  - Carbon monoxide dehydrogenases (CODHs) catalyze the reversible oxidation of
      carbon monoxide by reaction with water to yield carbon dioxide, two protons, and
      two electrons. Two principal types of CODHs can be distinguished. Ni,Fe
      containing CODHs contain a [NiFe(4)S(4)OH(x)] cluster within their active site,
      to which the direct binding of the substrates water and carbon dioxide has been
      revealed by protein X-ray crystallography. n-Butyl isocyanide is a slow-turnover
      substrate of CODHs, whose oxidation at the active site shows several parallels to
      the oxidation of carbon monoxide. Here, we report the crystal structure of CODH
      II from Carboxydothermus hydrogenoformans resulting from the enzymatic oxidation
      of n-butyl isocyanide to n-butyl isocyanate at its active site cluster. The high
      resolution of the structure (d(min) = 1.28 A) revealed n-butyl isocyanate bound
      to the active site cluster and identified a novel type of Ni-C bond in CODHs. The
      structure suggests the occurrence of tetrahedral in addition to square-planar
      nickel complexes in product-bound states of this enzyme. Furthermore, we
      discovered a molecule of n-butyl isocyanide in a hydrophobic channel leading to
      the active site, revealing a unique architecture for the substrate channel of
      CODH-II compared with the bifunctional CODHs.

PMID- 21904890
TI  - Metallothioneins: chemical and biological challenges.

PMID- 21904891
TI  - The effect of poly sterilization on wear, osteolysis and survivorship of a press
      fit cup at 10-year followup.
AB  - BACKGROUND: During the mid-1990s when our institution was using a press-fit
      porous-coated cup without supplemental initial fixation for primary THA, the
      manufacturer transitioned from gamma irradiation to gas plasma for the terminal
      sterilization of their polyethylene liners. QUESTIONS/PURPOSES: At minimum 10
      year followup, we asked whether the fixation achieved by solely relying on a
      press-fit would be durable and how different liner sterilization methods affected
      radiographic wear, osteolysis, and survivorship. PATIENTS AND METHODS: We
      retrospectively reviewed 373 patients who underwent 398 primary THAs with a press
      fit porous-coated cup between March 1995 and December 1996. Mean age at time of
      surgery was 61.5 +/- 13.3 years and mean followup was 10.4 +/- 3.7 years. We
      determined reasons for revision, survivorship, femoral head penetration,
      osteolysis, and wear-related complications. RESULTS: Among 20 revisions involving
      any component, seven were associated with wear and osteolysis. Kaplan-Meier
      survivorship, using component revision for any reason as an end point, was 95.7%
      (95% confidence interval, 93.6%-97.9%) at 10 years. Noncrosslinked liners
      sterilized with gas plasma demonstrated a mean head penetration rate of 0.20 +/-
      0.09 mm/year compared with 0.13 +/- 0.07 mm/year for liners sterilized with gamma
      irradiation in air and 0.09 +/- 0.04 mm/year for liners sterilized with gamma
      irradiation with barrier packaging without oxygen. THAs with increased volumetric
      wear tended to demonstrate larger osteolytic lesions (r = 0.40) and there tended
      to be less osteolysis among the liners sterilized with gamma-irradiation with
      barrier packaging without oxygen. However, there was no difference in
      survivorship among the sterilization groups and there has been no cup or stem
      loosening associated with osteolysis. CONCLUSIONS: Durable biologic fixation
      through 10-year followup can be achieved by solely relying on an initial press
      fit. Noncrosslinking gas plasma for terminal sterilization of the polyethylene
      liners was associated with greater head penetration rate than gamma irradiation.
      LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 21904892
TI  - Surgical technique: when to arthroscopically repair the torn posterior cruciate
      ligament.
AB  - BACKGROUND: Posterior cruciate ligament injuries can occur as isolated ligament
      ruptures or in association with the multiligament-injured knee. Delayed
      reconstruction, at 2-3 weeks post-injury, is predominantly recommended for
      posterior cruciate ligament tears in the multiligament-injured knee. While acute
      bone and soft tissue avulsion patterns of injury can be amenable to repair, the
      described techniques have been associated with some difficulties attaching the
      avulsed ligament. DESCRIPTION OF TECHNIQUE: As part of a reconstruction/repair of
      a multiligament-injured knee, we performed arthroscopic primary repair of the
      posterior cruciate ligament by passing Bunnell-type stitches into the substance
      of the ligament using a reloadable suture passer. We then passed the sutures
      through drill holes into the femoral footprint of the ligament and tied them over
      a bony bridge. PATIENTS AND METHODS: We retrospectively reviewed three patients
      with posterior cruciate ligament tears associated with a multiligament-injured
      knee. All patients had posterior cruciate ligament soft tissue avulsions or "peel
      off" injuries diagnosed by MRI. The described repair technique was used to repair
      the posterior cruciate ligament avulsion. Minimum followup was 64 months (mean,
      68 months; range, 64-75 months). ROM, stability testing, and functional outcome
      scores (Lysholm and modified Cincinnati) were recorded. RESULTS: Mean ROM was 0
      degrees  to 127 degrees . Posterior drawer testing was negative in all three
      patients. The mean Lysholm score was 92 and the mean modified Cincinnati score
      was 94. Followup MRI confirmed ligament healing in all patients. CONCLUSIONS: We
      believe arthroscopic posterior cruciate ligament repair for soft tissue peel off
      injuries is a technique that, when applied to carefully selected patients, may be
      helpful to the surgeon treating patients with a multiligament-injured knee. LEVEL
      OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a
      complete description of levels of evidence.

PMID- 21904893
TI  - [Genetics of contact allergy].
AB  - The genetics of contact allergy (CA) is still only partly understood, despite
      decades of research. This might be due to inadequately defined phenotypes used in
      the past. Therefore we suggested studying an extreme phenotype, namely,
      polysensitization (sensitization to 3 or more unrelated allergens). Another
      approach to unravel the genetics of CA has been the study of candidate genes. In
      this review, we summarize studies on the associations between genetic variation
      (e.g. SNPs) in certain candidate genes and CA. The following polymorphisms and
      mutations were studied: (1) filaggrin, (2) N-acetyltransferase (NAT1 and 2), (3)
      glutathione-S-transferase (GST M and T), (4) manganese superoxide dismutase, (5)
      angiotensin-converting enzyme (ACE), (6) tumor necrosis factor (TNF), and (7)
      interleukin-16 (IL16). The polymorphisms of NAT1/2, GST M/T, ACE, TNF, and IL16
      were shown to be associated with an increased risk of CA. In one of our studies,
      the increased risk conferred by the TNF and IL16 polymorphisms was confined to
      polysensitized individuals. Other relevant candidate genes may be identified by
      studying diseases related to CA in terms of clinical symptoms, a more general
      pathology (inflammation) and possibly an overlapping genetic background, such as
      irritant contact dermatitis.

PMID- 21904894
TI  - Microarray expression profiling in 6-hydroxydopamine-induced dopaminergic
      neuronal cell death.
AB  - Parkinson's disease (PD) is the second most common neurodegenerative disorder and
      is characterized by a loss of dopaminergic neurons in the substantia nigra pars
      compacta. To discover potential key molecules in this process, we utilized cDNA
      microarray technology to obtain an expression profile of transcripts in MN9D
      dopaminergic neuronal cells treated with 6-hydroxydopamine. Using a self
      organizing map algorithm, data mining and clustering were combined to identify
      distinct functional subgroups of genes. We identified alterations in the
      expression of 81 genes in eight clusters. Among these genes, we verified protein
      expression patterns of MAP kinase phosphatase 1 and sequestosome 1 using both
      cell culture and rat brain models of PD. Immunological analyses revealed
      increased expression levels as well as aggregated distribution patterns of these
      gene products in 6-hydroxydopamine-treated dopaminergic neurons. In addition to
      the identification of other proteins that are known to be associated with protein
      aggregation, our results raise the possibility that a more widespread set of
      proteins may be associated with the generation of protein aggregates in dying
      neurons. Further research to determine the functional roles of other altered gene
      products within the same cluster as well as the seven remaining clusters may
      provide new insights into the neurodegeneration that underlies PD pathogenesis.

PMID- 21904895
TI  - Subchronic elevation of brain kynurenic acid augments amphetamine-induced
      locomotor response in mice.
AB  - The neuromodulating tryptophan metabolite kynurenic acid (KYNA) is increased in
      the brain of patients with schizophrenia. In the present study we investigate the
      spontaneous locomotor activity as well as the locomotor response to d-amphetamine
      [5 mg/kg, administered intraperitoneal (i.p.)] after increasing endogenous levels
      of brain KYNA in mice by acute (10 mg/kg, i.p., 60 min) or subchronic (100 mg/kg
      i.p., twice daily for 6 days) pretreatment with the blood-brain crossing
      precursor, L: -kynurenine. We found that an acute increase in the brain KYNA
      levels caused increased corner time and percent peripheral activity but did not
      change the d-amphetamine-induced locomotor response. In contrast, subchronic
      elevation of KYNA did not change the spontaneous locomotor activity but produced
      an exaggerated d-amphetamine-induced hyperlocomotion. These results cohere with
      clinical studies of patients with schizophrenia, where a potentiated DA release
      associated with exacerbation of positive symptoms has been observed following d
      amphetamine administration. Present results further underscore KYNA as a possible
      mediator of the aberrant dopaminergic neurotransmission seen in schizophrenia.

PMID- 21904896
TI  - Effects of unilateral pedunculopontine stimulation on electromyographic
      activation patterns during gait in individual patients with Parkinson's disease.
AB  - In Parkinson's disease (PD), the effects of deep brain stimulation of the
      pedunculopontine nucleus (PPTg-DBS) on gait has been object of international
      debate. Some evidence demonstrated that, in the late swing-early stance phase of
      gait cycle, a reduced surface electromyographic activation (sEMG) of tibialis
      anterior (TA) is linked to the striatal dopamine deficiency in PD patients. In
      the present study we report preliminary results on the effect of PPTg-DBS on
      electromyographic patterns during gait in individual PD patients. To evaluate the
      sEMG amplitude of TA, the root mean square (RMS) of the TA burst in late swing
      early stance phase (RMS-A) was normalized as a percent of the RMS of the TA burst
      in late stance-early swing (RMS-B). We studied three male patients in the
      following conditions: on PPTg-DBS/on L: -dopa, on PPTg-DBS/off L: -dopa, off PPTg
      DBS/on L: -dopa, off PPTg-DBS/off L: -dopa. For each assessment the UPDRS III was
      filled in. We observed no difference between on PPTg-DBS/off L: -dopa and off
      PPTg-DBS/off L: -dopa in UPDRS III scores. In off PPTg-DBS/off L: -dopa, patient
      A (right implant) showed absence of the right and left RMSA, respectively, in 80%
      and 83% of gait cycles. Patient B (right implant) showed absence of the right RMS
      A in 86% of cycles. RMS-A of the patient C (left implant) was bilaterally normal.
      In on PPTg- DBS/off L: -dopa, no patient showed reduced RMS-A. Although the very
      low number of subjects we evaluated, our observations suggest that PPTg plays a
      role in modulating TA activation pattern during the steady state of gait.

PMID- 21904897
TI  - Classification of schizophrenia using feature-based morphometry.
AB  - The objective of this study was to use a combined local descriptor, namely scale
      invariance feature transform (SIFT), and a non linear support vector machine
      (SVM) technique to automatically classify patients with schizophrenia. The
      dorsolateral prefrontal cortex (DLPFC), considered a reliable neuroanatomical
      marker of the disease, was chosen as region of interest (ROI). Fifty-four
      schizophrenia patients and 54 age- and gender-matched normal controls were
      studied with a 1.5T MRI (slice thickness 1.25 mm). Three steps were conducted:
      (1) landmark detection and description of the DLPFC, (2) feature vocabulary
      construction and Bag-of-Words (BoW) computation for brain representation, (3) SVM
      classification which adopted the local kernel to implicitly implement the feature
      matching. Moreover, a new weighting approach was proposed to take into account
      the discriminant relevance of the detected groups of features. Substantial
      results were obtained for the classification of the whole dataset (left side 75%,
      right side 66.38%). The performances were higher when females (left side 84.09%,
      right side 77.27%) and seniors (left side 81.25%, right side 70.83%) were
      considered separately. In general, the supervised weighed functions increased the
      efficacy in all the analyses. No effects of age, gender, antipsychotic treatment
      and chronicity were shown on DLPFC volumes. This integrated innovative ROI-SVM
      approach allows to reliably detect subjects with schizophrenia, based on a
      structural brain marker for the disease such as the DLPFC. Such classification
      should be performed in first-episode patients in future studies, by considering
      males and females separately.

PMID- 21904898
TI  - [Acute aortic syndrome: a severe malignant disease pattern which requires
      systematic steps in diagnosis and therapy].

PMID- 21904899
TI  - [Hybrid room technology as a prerequisite for the modern therapy of aortic
      dissection].
AB  - With the establishment of a hybrid room 7 years ago, it was possible for the
      first time to unite a full range of diagnostics and surgical therapy under the
      sterile conditions of an operating theatre in life-threatening aortic dissection.
      Thus, the early phase associated with high mortality rates (3%-5% per hour) could
      be significantly reduced from 8 h to 4 h. Multidisciplinary teams consisting of a
      cardiac surgeon, a cardiologist and an anaesthetist enable competent and rapid
      life-saving measures. In the case of acute and persistent visceral and/or
      peripheral malperfusion over many hours, primary endovascular reconstitution of
      perfusion precedes delayed surgical replacement of the ascending aorta with or
      without the aortic arch. Additional strategic and technical surgical developments
      have helped reduce overall hospital mortality from 15%-20% to 10%-15%. Though
      expensive to build, a high-technology hybrid room enables interdisciplinary
      specialization and concentration, as demonstrated by the exponential growth in
      the development of transcatheter aortic valve implants or the endovascular
      treatment of aortic disease.

PMID- 21904900
TI  - [Modern aortic surgery in Marfan syndrome--2011].
AB  - Marfan syndrome is a hereditary disease with a prevalence of 2-3 in 10,000
      births, leading to a fibrillin connective tissue disorder with manifestations in
      the skeleton, eye, skin, dura mater and in particular the cardiovascular system.
      Since other syndromes demonstrate similar vascular manifestations, but therapy
      may differ significantly, diagnosis should be established using the revised Ghent
      nosology in combination with genotypic analysis in specialized Marfan centres.
      The formation of aortic root aneurysms with the subsequent risk of acute aortic
      dissection type A (AADA) or aortic rupture limits life expectancy in patients
      with Marfan syndrome. Therefore, prophylactic replacement of the aortic root
      needs to be performed before the catastrophic event of AADA can occur. The goal
      of surgery is the complete resection of pathological aortic tissue. This can be
      achieved with excellent results by using a (mechanically) valved conduit that
      replaces both the aortic valve and the aortic root (Bentall operation). However,
      the need for lifelong anticoagulation with Coumadin can be avoided using the
      aortic valve sparing reimplantation technique according to David. The long-term
      durability of the reconstructed valve is favourable, and further technical
      improvements may improve longevity. Although results of prospective randomised
      long-term studies comparing surgical techniques are lacking, the David operation
      has become the surgical method of choice for aortic root aneurysms, not only at
      the Heidelberg Marfan Centre. Replacement of the aneurysmal dilated aortic arch
      is performed under moderate hypothermic circulatory arrest combined with
      antegrade cerebral perfusion using a heart-lung machine, which we also use in
      thoracic or thoracoabdominal aneurysms. Close post-operative follow-up in a
      Marfan centre is pivotal for the early detection of pathological changes on the
      diseased aorta.

PMID- 21904901
TI  - Longitudinal changes in magnetisation transfer ratio in secondary progressive
      multiple sclerosis: data from a randomised placebo controlled trial of
      lamotrigine.
AB  - Sodium blockade with lamotrigine is neuroprotective in animal models of central
      nervous system demyelination. This study evaluated the effect of lamotrigine on
      magnetisation transfer ratio (MTR), a putative magnetic resonance imaging measure
      of intact brain tissue, in a group of subjects with secondary progressive
      multiple sclerosis (MS). In addition, the utility of MTR measures for detecting
      change in clinically relevant pathology was evaluated. One hundred seventeen
      people attending the National Hospital for Neurology and Neurosurgery or the
      Royal Free Hospital, London, UK, were recruited into a double-blind, parallel
      group trial. Subjects were randomly assigned by minimisation to receive
      lamotrigine (target dose 400 mg/day) or placebo for 2 years. Treating and
      assessing physicians and patients were masked to treatment allocation. Results of
      the primary endpoint, central cerebral volume, have been published elsewhere.
      Significant differences between the verum and placebo arms were seen in only two
      measures [normal appearing grey matter (NAGM) p = 0.036 and lesion peak height
      (PH) p = 0.004], and in both cases there was a greater reduction in MTR in the
      verum arm. Significant correlations were found of change in MS functional
      composite with all MTR measures except lesion and normal appearing white matter
      (NAWM) PH. However, the change in MTR measures over 2 years were small, with only
      NAGM mean (p = 0.001), lesion peak location (p = 0.11) and mean (p < 0.0001)
      changing significantly from baseline. These data did not show that lamotrigine
      was neuroprotective. The clinical correlation of MTR measures was consistent, but
      the responsiveness to change was limited.

PMID- 21904903
TI  - PI3K/Akt and MAPK/ERK1/2 signaling pathways are involved in IGF-1-induced VEGF-C
      upregulation in breast cancer.
AB  - OBJECTIVE: To investigate the signaling pathways involved in insulin-like growth
      factor-1 (IGF-1)-induced vascular endothelial growth factor C (VEGF-C) up
      regulation and lymphatic metastasis in MDA-MB-231 breast cancer cells. METHODS:
      MDA-MB-231 breast cancer cells were exposed to IGF-1 with various concentrations.
      The expression level of VEGF-C was assessed by real-time PCR and Western blot.
      Akt and ERK1/2 phosphorylation was detected by Western blot. Signaling
      transduction inhibitors, LY294002 and PD98059, were used to block PI3K/Akt and
      MAPK/ERK1/2 signaling pathways, respectively. RESULTS: IGF-1 increased the level
      of VEGF-C expression in a dose-dependent manner in MDA-MB-231 breast cancer
      cells. In addition, phosphorylation of Akt and ERK1/2 was enhanced by IGF-1.
      Remarkably, inhibition of Akt phosphorylation by LY294002 completely blocked the
      effects on IGF-1-induced VEGF-C up-regulation. Inhibition of ERK1/2
      phosphorylation by PD98059 reduced IGF-1-induced VEGF-C expression. CONCLUSION:
      This study identified that PI3K/Akt and MAPK/ERK1/2 signaling pathways were
      involved in IGF-1-induced VEGF-C up-regulation and suggested their important
      roles in lymphatic metastasis in breast cancer.

PMID- 21904904
TI  - Etoposide-mediated glioblastoma cell death: dependent or independent on the
      expression of its target, topoisomerase II alpha?
AB  - BACKGROUND: Treatments which significantly improve progression-free and overall
      survival for patients with relapsed glioblastoma (GBM) after the standard therapy
      are lacking. The Topoisomerase II (TopoII) enzyme is a key target of anticancer
      agents because of the important role it plays in transcription regulation and
      chromatin remodeling. A drug with strong topoisomerase-mediated anticancer
      activity is etoposide that is used in combination with carboplatin in patients
      with relapsed GBM. We hypothesized that tumors harboring high expression of
      TopoII alpha (TopoIIa) would be more sensitive to etoposide treatment. METHODS:
      The relative expression levels of TopoIIa protein were measured in a panel of GBM
      cell lines using Western blot analysis and in a cohort of GBM using
      immunohistochemistry. Expression levels of TopoIIa in the cell lines were
      correlated with relative sensitivity to treatment with etoposide. To ascertain
      the role TopoIIa plays in mediating response to etoposide, expression was reduced
      with a siRNA targeted to TopoIIa. RESULTS: Protein expression of TopoIIa,
      although high in the cell lines, was very low in patient specimens. Correlations
      between TopoIIa protein expression and sensitivity to etoposide were evident. The
      IC(50) for the low-TopoIIa-expressing cell line, T98G, was almost 50 times higher
      than M059K (high TopoIIa). Inhibition of TopoIIa in MO59K cells with siRNA
      significantly altered the IC(50), increasing the resistance to etoposide.
      Interestingly, the expression of TopoIIa was not decreased after treatment with
      etoposide, indicating other mechanisms underplay treatment response. CONCLUSIONS:
      In vitro, the levels of TopoIIa protein expression correlate with response to
      etoposide but also multiple molecular events namely DNA-PK and MDR also play a
      role in cell sensitivity to etoposide. That we did not find a high expression of
      TopoIIa in clinical specimens further suggests the mechanisms underlying
      treatment response are complex.

PMID- 21904905
TI  - OLFM4 is associated with lymph node metastasis and poor prognosis in patients
      with gastric cancer.
AB  - PURPOSE: The present study investigated the clinical significance of the
      relationship between olfactomedin 4 (OLFM4) expression and the
      clinicopathological features of patients with gastric cancer. METHODS: Tumor
      tissue and adjacent normal tissue, lymph nodes, and peritoneal metastases were
      analyzed by the Affymetrix GeneChip((r)) HG-U133A2.0 array. The expression of
      OLFM4 was detected by real-time quantitative RT-PCR in gastric tumor tissue and
      adjacent normal tissue. OLFM4 expression was analyzed by immunohistochemistry in
      436 clinicopathologically characterized gastric cancer cases and in corresponding
      distant metastases from 61 patients. RESULTS: A total of 434 genes and 169
      expressed sequence tags were upregulated, including OLFM4. The expression of
      OLFM4 mRNA or protein differed significantly among gastric tumor tissue, matched
      normal gastric mucosa, and lymph node metastases. Further multivariate analysis
      suggested that lymph node metastases and distant metastases, TNM stage, and
      expression of OLFM4 were independent prognostic indicators for gastric cancer.
      CONCLUSION: Gene expression profiles were useful for simultaneously analyzing the
      expression levels of thousands of genes. Reduced expression of OLFM4 in gastric
      cancer is associated significantly with lymph node and distant metastases and
      with poor prognosis. OLFM4 may prove to be an important molecular marker for
      predicting the carcinogenesis, development, progression, and metastasis of
      gastric cancer.

PMID- 21904906
TI  - Urate nephropathy associated with impaired kinetic properties of hypoxanthine
      phosphoribosyl transferase in a 45-day-old infant.
AB  - We report a 45-day-old male infant who presented with anuric renal failure and
      fluid overload due to urate nephropathy consequent upon hyperuricemia with
      hyperuricosuria. His maternal uncle had undergone renal transplantation for
      chronic renal failure secondary to uric acid nephrolithiasis. The levels of
      hypoxanthine phosphoribosyl transferase (HPRT) and adenine phosphoribosyl
      transferase activity in the baby were found to be quantitatively normal. However,
      when the HPRT activity was measured at low substrate concentrations
      [phosphoribosyl pyrophosphate (PRPP) and hypoxanthine] and compared with usual
      assay conditions, the HPRT activity at lower PRPP was less in the propositus,
      suggesting altered enzyme kinetics. Apparent K (m(PRPP)) and V (max), but not K
      (m(hypoxanthine)), were then found to be higher in the propositus than the
      control range. This is the first case of urate nephropathy secondary to altered
      enzyme kinetics presenting as early as 45 days. Uric acid nephropathy should be
      considered in the differential diagnosis of unexplained acute kidney injury in
      infants. In such cases, quantitative tests for HPRT enzyme activity may not be
      sufficient and altered enzyme kinetics should also be investigated.

PMID- 21904902
TI  - HIV-related research in correctional populations: now is the time.
AB  - The incarcerated population has increased to unprecedented levels following the
      1970 US declaration of war on illicit drug use. A substantial proportion of
      people with or at risk for HIV infection, including those with substance use and
      mental health disorders, have become incarcerated. The overlapping epidemics of
      incarceration and HIV present a need for academic medical centers to collaborate
      with the criminal justice system to improve the health of incarcerated
      populations. With coordinated collaboration and new programmatic initiatives it
      is possible to reduce HIV-associated risk behaviors and the likelihood of
      acquisition and transmission of HIV. Centers for AIDS Research (CFAR), funded by
      the National Institutes of Health, have proactively responded to this need
      through Collaboration on HIV in Corrections (CHIC) to improve the diagnosis,
      treatment, linkage to care, and prevention of HIV. This collaboration serves as a
      model for aligning academic expertise with criminal justice to confront this
      challenge to individual and public health. This is especially relevant given
      recent evidence of the effectiveness of antiretroviral therapy in reducing HIV
      transmission.

PMID- 21904907
TI  - Validation of the equations for estimating daily sodium excretion from spot urine
      in patients with chronic kidney disease.
AB  - BACKGROUND: Measuring sodium excretion in a 24-h urine collection is the most
      reliable method of estimating salt intake, but it is not applicable to all
      patients. As an alternative, equations for estimating Na excretion from Japanese
      by a spot urine sample were created, but they have not been validated in patients
      with chronic kidney disease (CKD), which are frequently associated with nocturia
      and medication. METHODS: We enrolled 136 patients with CKD and collected both 24
      h urine and the first morning urine. Na excretion was estimated from the first
      morning urine by Kawasaki's equation, which was originally used for the second
      morning urine, and Tanaka's equation, which is applied for spot urine samples
      taken at any time from 9 am to 7 pm. We evaluated the two equations for bias,
      RMSE and accuracy within 30 and 50% of the measured Na excretion. RESULTS: Bias,
      RMSE and accuracy within 30% of the estimated Na excretion were 48 +/- 69 and 2
      +/- 69 mmol/day, 84 and 69 mmol/day, and 35 and 49% using Kawasaki's equation and
      Tanaka's equation, respectively. Na excretion in the first morning urine was
      accurately estimated by Tanaka's equation, but it was overestimated by Kawasaki's
      equation. Nocturia and medication such as diuretics and ACE inhibitor or
      angiotensin receptor blocker did not affect the accuracy with which Na excretion
      was estimated by Tanaka's equation substantially. CONCLUSION: Tanaka's equation
      for estimating Na excretion from the first morning urine in patients with CKD is
      accurate enough for use in clinical practice.

PMID- 21904908
TI  - Efficient molecular mechanics simulations of the folding, orientation, and
      assembly of peptides in lipid bilayers using an implicit atomic solvation model.
AB  - Membrane proteins comprise a significant fraction of the proteomes of sequenced
      organisms and are the targets of approximately half of marketed drugs. However,
      in spite of their prevalence and biomedical importance, relatively few
      experimental structures are available due to technical challenges. Computational
      simulations can potentially address this deficit by providing structural models
      of membrane proteins. Solvation within the spatially heterogeneous
      membrane/solvent environment provides a major component of the energetics driving
      protein folding and association within the membrane. We have developed an
      implicit solvation model for membranes that is both computationally efficient and
      accurate enough to enable molecular mechanics predictions for the folding and
      association of peptides within the membrane. We derived the new atomic solvation
      model parameters using an unbiased fitting procedure to experimental data and
      have applied it to diverse problems in order to test its accuracy and to gain
      insight into membrane protein folding. First, we predicted the positions and
      orientations of peptides and complexes within the lipid bilayer and compared the
      simulation results with solid-state NMR structures. Additionally, we performed
      folding simulations for a series of host-guest peptides with varying propensities
      to form alpha helices in a hydrophobic environment and compared the structures
      with experimental measurements. We were also able to successfully predict the
      structures of amphipathic peptides as well as the structures for dimeric
      complexes of short hexapeptides that have experimentally characterized
      propensities to form beta sheets within the membrane. Finally, we compared
      calculated relative transfer energies with data from experiments measuring the
      effects of mutations on the free energies of translocon-mediated insertion of
      proteins into lipid bilayers and of combined folding and membrane insertion of a
      beta barrel protein.

PMID- 21904909
TI  - Distinct functional and conformational states of the human lymphoid tyrosine
      phosphatase catalytic domain can be targeted by choice of the inhibitor
      chemotype.
AB  - The lymphoid tyrosine phosphatase (LYP), encoded by the PTPN22 gene, has recently
      been identified as a promising drug target for human autoimmunity diseases. Like
      the majority of protein-tyrosine phosphatases LYP can adopt two functionally
      distinct forms determined by the conformation of the WPD-loop. The WPD-loop plays
      an important role in the catalytic dephosphorylation by protein-tyrosine
      phosphatases. Here we investigate the binding modes of two chemotypes of small
      molecule LYP inhibitors with respect to both protein conformations using
      computational modeling. To evaluate binding in the active form, we built a LYP
      protein structure model of high quality. Our results suggest that the two
      different compound classes investigated, bind to different conformations of the
      LYP phosphatase domain. Binding to the closed form is facilitated by an
      interaction with Asp195 in the WPD-loop, presumably stabilizing the active
      conformation. The analysis presented here is relevant for the design of
      inhibitors that specifically target either the closed or the open conformation of
      LYP in order to achieve better selectivity over phosphatases with similar binding
      sites.

PMID- 21904911
TI  - A novel canine model of portal vein stenosis plus thioacetamide administration
      induced cirrhotic portal hypertension with hypersplenism.
AB  - Current large animal models that could closely resemble the typical features of
      cirrhotic portal hypertension in human have not been well established. Thus, we
      aimed to develop and describe a reliable and reproducible canine cirrhosis model
      of portal hypertension. A total of 30 mongrel dogs were randomly divided into
      four groups: 1 (control; n = 5), 2 (portal vein stenosis [PVS]; n = 5], 3
      (thioacetamide [TAA]; n = 5), and 4 (PVS plus TAA; n = 15). After 4-months
      modeling period, liver and spleen CT perfusion, abdominal CT scans, portal
      hemodynamics, gastroscopy, hepatic function, blood routine, the bone marrow,
      liver, and spleen histology were studied. The animals in group 2 (PVS) developed
      extrahepatic portosystemic collateral circulation, particularly esophageal
      varices, without hepatic cirrhosis and portal hypertension. Animals from group 3
      (TAA) presented mild cirrhosis and portal hypertension without significant
      symptoms of esophageal varices and hypersplenism. In contrast, animals from group
      4 (PVS + TAA) showed well-developed micronodular and macronodular cirrhosis,
      associated with significant portal hypertension and hypersplenism. The
      combination of PVS and TAA represents a novel, reliable, and reproducible canine
      cirrhosis model of portal hypertension, which is associated with the typical
      characteristics of portal hypertension, including hypersplenism.

PMID- 21904910
TI  - Sperm DNA integrity assays: diagnostic and prognostic challenges and implications
      in management of infertility.
AB  - Sperm is not a simple carrier of paternal genetic information but its role
      extends clearly beyond fertilization. Integrity of sperm genome is an essential
      pre-requisite for birth of healthy offspring and evaluation of sperm should
      entail DNA integrity analysis. DNA integrity analysis is a better diagnostic and
      prognostic marker of sperm reproductive potential. Conventional semen analysis
      emphasizes on sperm concentration, viability, motility and morphology and has
      been proven to be a poor indicator of reproductive potential and pregnancy
      outcome. To overcome the drawbacks associated with conventional semen analysis
      more useful fertility tests and molecular biomarkers have been explored. Among
      the different tests which have evolved for assessing the sperm reproductive
      potential, tests for sperm DNA quality are most promising. Sperm DNA damage has
      been closely associated with numerous indicators of reproductive health including
      fertilization, embryo quality, implantation, spontaneous abortion, congenital
      malformations and childhood diseases. It therefore has great potential as a
      prognostic test for both in vitro and in vivo conception. This review presents an
      updated account of tests that have better diagnostic and prognostic implications
      in the evaluation of sperm DNA damage. The basic principles, outline of
      methodology, advantage, disadvantage, clinical significance of each technique and
      implications of these tests have been discussed. The logistics of each test with
      respect to available resources and equipment in an andrology laboratory, the
      feasibility of performing these tests in routine diagnostic workup of infertile
      men and the opportunities and challenges provided by DNA testing in male
      fertility determination are also presented.

PMID- 21904912
TI  - The use of an early postoperative CRH test to assess adrenal function after
      transsphenoidal surgery for pituitary adenomas.
AB  - Transsphenoidal surgery (TS) is the treatment of choice for many pituitary
      tumors. Because TS may cause pituitary insufficiency in some of these patients,
      early postoperative assessment of pituitary function is essential for appropriate
      endocrine management. The aim of our study was to evaluate the clinical relevance
      of the CRH-stimulation test in assessing postoperative pituitary-adrenal
      function. We performed a retrospective analysis of 144 patients treated by TS
      between January 1990 and November 2009, in whom a CRH-test and a second
      stimulation test was performed to assess adrenal function during follow-up.
      Patients with Cushing's disease were excluded. Hydrocortisone substitution was
      started if peak cortisol levels were <550 nmol/L. The cortisol response was
      insufficient in 42(29%) and sufficient in 102 patients at the postoperative CRH
      test. Thirteen of 42(30%) demonstrated a normal cortisol response during a second
      cortisol stimulation test. In 75 of the 102 patients with a sufficient response
      to CRH repeat testing revealed an insufficient cortisol response in 14 patients
      (14%). All but one had concomitant pituitary hormone deficits. There were no
      cases of adrenal crises during follow-up. Additional pituitary insufficiency was
      significantly more present (P < 0.001) in the group of patients with an abnormal
      response to CRH directly after surgery. In this study a substitution strategy of
      hydrocortisone guided by the postoperative cortisol response to CRH appeared safe
      and did not result in any case of adrenal crises. However, the early
      postoperative CRH-test does not reliably predict adrenal function after TS for
      pituitary adenomas in all patients and retesting is mandatory.

PMID- 21904913
TI  - In planta expression of a mature Der p 1 allergen isolated from an Italian strain
      of Dermatophagoides pteronyssinus.
AB  - European (Dermatophagoides pteronyssinus) and American (Dermatophagoides farinae)
      house dust mite species are considered the most common causes of asthma and
      allergic symptoms worldwide. Der p 1 protein, one of the main allergens of D.
      pteronyssinus, is found in high concentration in mites faecal pellets, which can
      became easily airborne and, when inhaled, can cause perennial rhinitis and
      bronchial asthma. Here we report the isolation of the Der p 1 gene from an
      Italian strain of D. pteronyssinus and the PVX-mediated expression of its mature
      form (I-rDer p 1) in Nicotiana benthamiana plants. Human sera from characterized
      allergic patients were used for IgE binding inhibition assays to test the
      immunological reactivity of I-rDer p 1 produced in N. benthamiana plants. The
      binding properties of in planta produced I-rDer p 1 versus the IgE of patients
      sera were comparable to those obtained on Der p 1 preparation immobilized on a
      microarray. In this paper we provide a proof of concept for the production of an
      immunologically active form of Der p 1 using a plant viral vector. These results
      pave the way for the development of diagnostic allergy tests based on in planta
      produced allergens.

PMID- 21904914
TI  - Natural killer cell receptor-expressing innate lymphocytes: more than just NK
      cells.
AB  - Recently, additional subsets that extend the family of innate lymphocytes have
      been discovered. Among these newly identified innate lymphoid cells is a subset
      sharing phenotypic characteristics of natural killer cells and lymphoid tissue
      inducer cells. These cells co-express the transcription factor RORgammat and
      activating NK cell receptors (NKR), but their lineage and functional qualities
      remain poorly defined. Here, we discuss recent proposals to place these
      NKR(+)RORgammat(+) innate lymphocytes on hematopoietic lineage maps. An overview
      of the transcriptional circuitry determining fate decisions of innate lymphocytes
      and a summary of current concepts concerning plasticity and stability of innate
      lymphocyte effector fates are provided. We will conclude by discussing the
      function of RORgammat-expressing innate lymphocytes during inflammatory bowel
      diseases and in the immune response to tumors.

PMID- 21904915
TI  - Behavioural plasticity and sex differences in host finding of a specialized bee
      species.
AB  - Many animals feed on flowers, and visual as well as olfactory cues are considered
      as most important mediators in animal-plant interactions. However, the relative
      importance of these cues is not well understood. Bees are the most important
      animal pollinators worldwide and here, we determined the importance of decoupled
      and combined visual and olfactory cues of Lysimachia punctata (Primulaceae) for
      host plant location in both sexes of the specialized, solitary bee, Macropis
      fulvipes (Melittidae). Lysimachia-inexperienced female bees preferred olfactory
      over visual cues though visual cues increased the attractiveness of olfactory
      ones. In experienced females, the importance of visual cues was increased. Both
      Lysimachia-naive and -experienced males relied more on visual cues as compared to
      females. This study demonstrates that the relative weighting of cues used for
      host plant finding depends on the sex and experience of M. fulvipes. The latter
      finding reveals the presence of learning-induced behavioural plasticity in host
      plant finding for a bee species. It may allow the bee to forage highly efficient.
      Visually guided female detection on flowers by males is a likely functional
      explanation for the differences in the weighting of visual and olfactory cues
      between the sexes.

PMID- 21904916
TI  - Effects of lysophospholipids on tumor microenvironment.
AB  - The effects of lysophospholipids (LPLs) on cancer microenvironment is a vast and
      growing field. These lipids are secreted physiologically by various cell types.
      They play highly important roles in the development, activation and regulation of
      the immune system. They are also secreted by cancerous cells and there is a
      strong association between LPLs and cancer. It is clear that these lipids and in
      particular sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) play
      major roles in regulating the growth of tumor cells, and in manipulating the
      immune system. These activities can be divided into two parts; the first involves
      the ability of S1P and LPA to either directly or through some of the enzymes that
      generate them such as sphingosine kinases or phospholipases, induce the motility
      and invasiveness of tumor cells. The second mechanism involves the recently
      discovered effects of these lipids on the anti-tumor effector natural killer (NK)
      cells. Whereas S1P and LPA induce the recruitment of these effector cells, they
      also inhibit their cytolysis of tumor cells. This may support the environment of
      cancer and the ability of cancer cells to grow, spread and metastasize.
      Consequently, LPLs or their receptors may be attractive targets for developing
      drugs in the treatment of cancer where LPLs or their receptors are up-regulated.

PMID- 21904917
TI  - Evaluation of saliva flow rates, Candida colonization and susceptibility of
      Candida strains after head and neck radiation.
AB  - Hyposalivation is a long-term effect in patients receiving head and neck
      radiation. Radiotherapy can predispose oral colonization by Candida species of
      the mucosa. This study aims to evaluate the correlation between hyposalivation,
      measured by unstimulated saliva flow rates (SFR) and fungal colonization of the
      oral cavity, and also the resistance of isolated Candida strains to antimicrobial
      therapy. Fifty-three consecutive patients with radiotherapy were examined for
      late radiation damage on dental hard tissue and the salivary glands (SFR over a
      period of 5 min). The SFR were divided into three different values of
      hyposalivation: grade I (SFR 0.1-0.25 ml/min), grade II (SFR <=0.1 ml/min), and
      grade III (SFR = 0.0 ml/min). Candidal colonization was defined using Sabouraud
      agar and identified using API 20C AUX (biomerieux) in the patients' rinsing
      water. Susceptibility was tested with Etest (amphotericin B, ketoconacole,
      voriconacole, and fluconacole). Hyposalivation grade I was detected in 23% (9.1 *
      10(1) colony forming units (cfu); range, 200-5,900 cfu), hyposalivation grade II
      in 26% (4.3 * 10(1) cfu; range, 110-3,300 cfu), and hyposalivation grade III in
      51% (2.0 * 10(3) cfu; range, 300-19,475 cfu) of patients. A significant
      correlation between the SFR and candidal colonization and clinical presentation
      (European Organization for Research and Treatment of Cancer (EORTC) score) was
      detected (Mann-Whitney test, p = 0.031). Twenty Candida albicans and 27 non
      albicans species were identified. The resistance of C. albicans was higher than
      that of non-albicans strains against antimicrobial agents. By comparison,
      amphotericin B showed the greatest and fluconazole the least effect. A higher
      value of hyposalivation correlates with a higher risk of candidal colonization in
      patients who have received radiotherapy and also with a higher EORTC score. The
      spectrum of Candida is wide and susceptibility against antifungal therapy
      differs. In long-term examinations of patients with xerostomia after
      radiotherapy, the EORTC score can be used to measure hyposalivation. Reduced
      susceptibility of C. albicans might introduce complications to therapy. Findings
      of more non-albicans strains show a change in colonization which should be
      examined in further studies.

PMID- 21904918
TI  - Neurologic manifestations of Chagas disease.
AB  - Chagas disease is endemic in Latin America and has become an emerging problem in
      developed countries because of international migrations. The protozoan
      Trypanosoma cruzi is the etiologic agent and the disease is divided into two
      phases. The acute phase is mostly asymptomatic or presents with unspecific
      symptoms. Rarely, a severe and often fatal form occurs in immunosuppressed
      patients or infants, characterized by meningoencephalitis (sometimes including
      brain tumor-like lesions) and myocarditis. The chronic phase consists of an
      indeterminate, asymptomatic form followed by digestive, cardiac, or neurologic
      symptoms in about 30% of infected patients. Autonomous nervous system dysfunction
      is prominent in chagasic patients and participates in the affliction of the
      target organs. Stroke, mainly cardioembolic, may occur in the chronic phase, but
      other stroke etiologies are reported. Embolic sources and inflammation are
      thought to play a role in stroke mechanisms. Specific treatment for Chagas
      disease is scarce and preventive measures are needed.

PMID- 21904919
TI  - Borderzone strokes and transcortical aphasia.
AB  - Borderzone infarcts (BZIs) are anatomically defined as ischemic lesions occurring
      at the junction between two arterial territories, accounting for 2% to 10% of
      strokes. Three types of hemispheric BZIs are described according to topography
      (ie, superficial anterior, posterior, and deep). Although published series on
      related aphasia are rare in the setting of BZI, aphasia is of transcortical (TCA)
      type, characterized by the preservation of repetition. TCA can be of motor,
      sensory, or mixed type depending on whether expression, understanding, or both
      are impaired. Recent studies have reported specific aphasic patterns. BZI
      patients initially presented with mixed TCA. Aphasia specifically evolved
      according to the stroke location, toward motor or sensory TCA in patients with
      respectively anterior or posterior BZI. TCA was associated with good long-term
      prognosis. This specific aphasic pattern is interesting in clinical practice
      because it prompts the suspicion of a BZI before the MRI is done, and it helps in
      the planning of rehabilitation and in providing adapted information to the
      patient and family concerning the likelihood of language recovery.

PMID- 21904920
TI  - Does partial nephrectomy at an academic institution result in better outcomes?
AB  - PURPOSE: Partial nephrectomy (PN) outcomes may be better at academic institutions
      than at non-academic centers. Peer-review, sub-specialized practice profile,
      higher individual surgeon and institutional caseload may explain this
      observation. To the best of our knowledge, the role of institutional academic
      affiliation has not been examined with regard to PN postoperative outcomes.
      METHODS: Within the Health Care Utilization Project Nationwide Inpatient Sample
      (NIS), we focused on PNs performed within the 10 most contemporary years (1998
      2007). We explored the effect of academic status on three short-term PN outcomes
      (intraoperative and postoperative complications, as well as in-hospital
      mortality). Multivariable logistic regression analyses further adjusted for age,
      race, gender, Charlson Comorbidity Index (CCI), surgical approach, hospital
      region, annual hospital caseload and insurance status. RESULTS: Overall, 8,513
      PNs were identified. Of those, 5,906 (69.4%) were recorded at academic
      institutions. Academic institution patients had lower CCI, were less frequently
      Caucasian and more frequently had private insurance (all P < 0.001). Academic
      institution PNs were associated with fewer postoperative complications (14.6% vs.
      16.6%, P = 0.018). In multivariable analyses, institutional academic status did
      not affect the three short-term PN outcomes. CONCLUSIONS: Patient selection
      explains better PN postoperative outcomes at academic institutions. Control for
      these biases removes the outcome differences, at least when the three short-term
      PN outcomes are considered. However, the interpretation of these findings needs
      to take into account the lack of adjustment for case complexity.

PMID- 21904921
TI  - Single-port transvesical enucleation of the prostate for benign prostatic
      hyperplasia with severe intravesical prostatic protrusion.
AB  - OBJECTIVES: To introduce the surgical techniques of a single-port transvesical
      enucleation of the prostate (STEP) for enlarged prostates with severe
      intravesical prostatic protrusion (IPP) presenting with lower urinary tract
      symptoms (LUTS). PATIENTS AND METHODS: Our study included 7 patients with
      prostates larger than 80 mL and with severe IPP who underwent STEP. All the
      procedures were performed using a home-made single-port device through a 3-cm
      midline incision at the level three fingerbreadths above the symphysis pubis.
      Rigid laparoscopic instruments and Harmonic Scalpels((r)) were used to enucleate
      the large adenoma of the prostate. RESULTS: All the procedures were completed
      satisfactorily, with no intra and early postoperative complications. The mean
      resected prostatic weight was 54.14 +/- 8.38 g, and the mean operative time was
      191.86 +/- 40.88 min. The mean time for catheterization was 5.29 +/- 1.80 days.
      The postoperative 3-month international prostate symptoms score (IPSS) and
      maximal flow rate (Qmax) were improved following STEP (IPSS; 23.57 +/- 2.15 vs.
      11.43 +/- 2.44, Qmax; 17.14 +/- 3.44 mL/s vs. 6.71 +/- 2.29 mL/s). CONCLUSIONS:
      Laparoendoscopic single-site surgery (LESS) and enucleation of the prostate with
      rigid laparoscopic instruments might be difficult but is feasible. STEP may be a
      new treatment option for use in open prostatectomies for enlarged prostates with
      severe IPP in carefully selected patients.

PMID- 21904922
TI  - Effects of antiglaucoma drugs on the ocular surface in rabbits: a fixed
      combination drug versus two concomitant drugs.
AB  - PURPOSE: We investigated the effects of a fixed-combination antiglaucoma drug and
      compared it with two concomitant antiglaucoma drugs on the ocular surface.
      METHODS: Twenty-four rabbits were randomized into four groups. Group 1 was
      administered timolol, group 2 travoprost, group 3 a travoprost/timolol fixed
      combination solution, and group 4 timolol and travoprost. Conjunctival impression
      cytology specimens were collected at baseline and weeks 1, 3, and 6, and
      conjunctival biopsy specimens at week 6. RESULTS: The impression cytology study
      results were as follows: No statistically significant differences among group 1-3
      at any time (p > 0.05); a statistically significant difference between groups 3
      and 4 at week 6 (p = 0.003); a statistically significant difference between
      baseline and group 4 at week 6 (p = 0.008). Conjunctival biopsy specimens of
      group 1-3 showed no distortion of the conjunctival epithelial structures, but
      group 4 showed decreased layers of epithelial cells with fewer periodic acid
      Schiff (PAS) (+) goblet cells. CONCLUSIONS: A fixed-combination antiglaucoma drug
      is beneficial in reducing adverse ocular surface changes in long-term use. This
      is believed to be due to the smaller concentration of preservatives contained in
      the fixed-combination drug.

PMID- 21904923
TI  - Tolerogenic dendritic cells and rheumatoid arthritis: current status and
      perspectives.
AB  - Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the
      influxation of synovia and synovial compartments with immune cells including
      dendritic cells (DCs). DCs that induce autoimmune tolerance are called
      tolerogenic DCs (tolDCs). As a promising immunotherapeutic strategy for RA,
      tolDCs have received increasing attention. In this review, we first introduce the
      significant role of tolDCs in autoimmune regulation and then describe the
      manipulation strategies to generate tolDCs; next, we summarize recent progress in
      the experimental application of tolDCs for RA therapy, and finally we discuss the
      perspectives of tolerogenic vaccination for the treatment for RA in clinic.

PMID- 21904925
TI  - Management of psoriasis and psoriatic arthritis in a combined dermatology and
      rheumatology clinic.
AB  - Psoriasis and psoriatic arthritis (PsA) are chronic systemic inflammatory
      disorders with wide spectrums of cutaneous and musculoskeletal presentations.
      Management of joint disease in this population can be challenging and often
      requires the expertise of rheumatology in conjunction with dermatology. A
      multidisciplinary clinic setting may benefit these patients, and in this study we
      sought to evaluate the experience of such a model. We performed a retrospective
      chart review of patients evaluated between October 2003 and October 2009 in the
      Center for Skin and Related Musculoskeletal Diseases (SARM) at Brigham and
      Women's Hospital, Boston, MA, USA, where patients are seen by both an attending
      rheumatologist and dermatologist. Main outcomes included the presence of
      comorbidities, accuracy of the initial diagnosis, and escalation of treatment
      modalities. Over the 6-year period, 510 patients were evaluated. Two hundred
      sixty-eight patients had psoriasis and/or PsA. The prevalence of comorbidities
      was high (45% hypertension, 46% hyperlipidemia, 19% diabetes, and 36% history of
      the past or current smoking). Visit in SARM resulted in a revised diagnosis that
      differed from the previous diagnosis at outside clinics in 46% of cases. Patients
      were more likely to receive a systemic medication after the evaluation in SARM as
      compared to before, 25 versus 15%, respectively, with an odds ratio of 5.1.
      Patients were also more likely to be treated with a biologic agent after the
      evaluation in SARM as compared to before, 37 versus 16%, respectively.
      Multidisciplinary care may facilitate the diagnosis of joint disease and offers a
      more comprehensive treatment approach for patients with both psoriasis and PsA.
      Our data can be used to support the efforts to provide integrated rheumatologic
      and dermatologic care for this population.

PMID- 21904924
TI  - Confirmation of C4 gene copy number variation and the association with systemic
      lupus erythematosus in Chinese Han population.
AB  - The distribution of complement component 4 (C4) gene copy number (GCN) has been
      validated in European populations. Meanwhile, C4 gene has been identified as a
      susceptibility gene for systemic lupus erythematosus (SLE). However, the
      association and the possible phenotype significance remain to be determined
      intensely in the Chinese population. This study was designed to validate the
      distribution of C4 GCNs in Chinese Han and the correlation between C4 GCNs and
      SLE using quantitative real-time polymerase chain reaction in 924 SLE patients
      and 1,007 controls. The results presented distribution of C4 GCNs in healthy
      populations and also showed that lower C4 GCN was a risk factor for SLE and
      higher C4 GCN was a protective factor against the disease susceptibility, which
      was similar to the report in the Caucasian population. Furthermore, we found the
      association between C4A GCN and disease subphenotypes of arthritis with SLE. We
      conclude that the association of C4 GCN with SLE was replicated in Chinese Han
      population, which highlighted the importance of C4 in SLE pathogenesis of diverse
      populations.

PMID- 21904926
TI  - Significance of anatomic resection for early and advanced hepatocellular
      carcinoma.
AB  - PURPOSE: Although it remains controversial whether local ablation or surgery is
      better for early-stage hepatocellular carcinoma (HCC), surgical resection is the
      first choice for advanced HCC. Anatomic hepatic resection is the preferred
      procedure to improve prognosis, but to date, its superiority has been
      demonstrated only for early-stage HCC. This study aimed to evaluate the effect of
      anatomic resection in advanced HCC in which surgical resection is the first
      choice. METHODS: The prognosis of 210 patients who underwent curative resection
      for primary HCC was analyzed. Sixty-three patients with no more than three
      tumors, none of which were larger than 3 cm in diameter, and with no macroscopic
      vascular invasion were classified as early HCC (group E); the other 147 patients
      were classified as advanced HCC (group A). RESULTS: The 5-year survival rate was
      better in group E (73% vs. 55%, P < 0.01), but the 5-year recurrence-free
      survival rate was equivalent between the two groups (E vs. A; 30% vs. 32%, P =
      0.19). Multivariate analysis showed that independent predictors of good survival
      in group E were indocyanine green retention rate at 15 min <=20% [hazard ratio
      (HR) = 0.30; 95% confidential interval (CI),  0.10-0.88) and tumor
      differentiation grade of well or moderate or complete necrosis (HR = 0.14; 95%
      CI,  0.03-0.95), while predictors in group A were anatomic resection (HR = 0.48;
      95% CI,  02.27-0.85) and no macroscopic vascular invasion (HR = 0.35; 95% CI, 
      0.17-0.72). CONCLUSION: For advanced HCC, anatomic resection should be performed
      to improve patient prognosis.

PMID- 21904927
TI  - Successful treatment of nummular headache with Neurotropin(r).

PMID- 21904928
TI  - On-line effects of quadripulse transcranial magnetic stimulation (QPS) on the
      contralateral hemisphere studied with somatosensory evoked potentials and near
      infrared spectroscopy.
AB  - To evaluate on-line effects of quadripulse stimulation (QPS) over the primary
      motor cortex (M1) on cortical areas in the contralateral hemisphere. QPS
      consisted of 24 bursts of transcranial magnetic stimulation (TMS) pulses with an
      inter-burst interval of 5 s for 2 min (for on-line effect study) or 360 bursts
      for 30 min (for after-effect study). Each burst consisted of four TMS pulses
      (i.e. QPS) separated by an interstimulus interval of 5 or 50 ms (QPS-5 or QPS
      50). QPSs were delivered over the left M1. Experiment 1 [on-line effect on
      somatosensory evoked potential (SEP)]: Left median nerve SEPs were recorded
      before, during and after QPS. Experiment 2 (after effect on SEP): After-effects
      of QPS were evaluated by following up SEPs after the QPS sessions. Experiment 3
      (on-line effect on NIRS): Near infrared spectroscopy (NIRS) was also recorded at
      the right hemisphere during all QPS paradigms. Both QPS-5 and QPS-50 enlarged a
      cortical component of the contralateral SEP during stimulation. On the other
      hand, concerning the after effects, QPS-5 over M1 potentiated the contralateral
      SEP and QPS-50 tended to depress it. In NIRS study, both QPS-5 and QPS-50 induced
      a significant oxy-Hb decrease (deactivation pattern) at the right hemisphere
      during stimulation whereas sham stimulations unaffected them. We have shown the
      unidirectional on-line effects evoked by QPS-5 and QPS-50 on both SEP and NIRS,
      and bidirectional after effects on SEP at the contralateral hemisphere. The
      discrepancy between on-line effect and after effect may be explained by the
      differences in the underlying mechanisms between them. The former may be mainly
      explained by pure electrophysiological property changes in the membrane or
      synapses. The latter may be explained by synaptic efficacy changes which need
      some protein syntheses at least partly. Another discrepancy shown here is the
      direction of on-line effects. Electrophysiological (SEP) function was potentiated
      by both QPSs whereas hemodynamic (NIRS) function was depressed. This may be
      explained by which sensory areas contribute to NIRS or SEP generation.

PMID- 21904929
TI  - Mechanism of functional recovery after repetitive transcranial magnetic
      stimulation (rTMS) in the subacute cerebral ischemic rat model: neural plasticity
      or anti-apoptosis?
AB  - Repetitive transcranial magnetic stimulation (rTMS) has been studied increasingly
      in recent years to determine whether it has a therapeutic benefit on recovery
      after stroke. However, the underlying mechanisms of rTMS in stroke recovery
      remain unclear. Here, we evaluated the effect of rTMS on functional recovery and
      its underlying mechanism by assessing proteins associated with neural plasticity
      and anti-apoptosis in the peri-lesional area using a subacute cerebral ischemic
      rat model. Twenty cerebral ischemic rats were randomly assigned to the rTMS or
      the sham group at post-op day 4. A total of 3,500 impulses with 10 Hz frequency
      were applied to ipsilesional cortex over a 2-week period. Functional outcome was
      measured before (post-op day 4) and after rTMS (post-op day 18). The rTMS group
      showed more functional improvement on the beam balance test and had stronger Bcl
      2 and weaker Bax expression on immunohistochemistry compared with the sham group.
      The expression of NMDA and MAP-2 showed no significant difference between the two
      groups. These results suggest that rTMS in subacute cerebral ischemia has a
      therapeutic effect on functional recovery and is associated with an anti
      apoptotic mechanism in the peri-ischemic area rather than with neural plasticity.

PMID- 21904930
TI  - Imitation of hand and tool actions is effector-independent.
AB  - Following the theoretical notion that tools often extend one's body, in the
      present study, we investigated whether imitation of hand or tool actions is
      modulated by effector-specific information. Subjects performed grasping actions
      toward an object with either a handheld tool or their right hand. Actions were
      initiated in response to pictures representing a grip at an object that could be
      congruent or incongruent with the required action (grip-type congruency).
      Importantly, actions could be cued by means of a tool cue, a hand cue, and a
      symbolic cue (effector-type congruency). For both hand and tool actions, an
      action congruency effect was observed, reflected in faster reaction times if the
      observed grip type was congruent with the required movement. However, neither
      hand actions nor tool actions were differentially affected by the effector
      represented in the picture (i.e., when performing a tool action, the action
      congruency effect was similar for tool cues and hand cues). This finding suggests
      that imitation of hand and tool actions is effector-independent and thereby
      supports generalist rather than specialist theories of imitation.

PMID- 21904931
TI  - The impacts of modern warfare on freshwater ecosystems.
AB  - There is increasing recognition and concern regarding the impacts of modern
      industrial warfare on the environment. Freshwater ecosystems are perhaps the most
      vulnerable to warfare-related impacts, which is of concern given that they
      provide so many essential environmental resources and services to society.
      Despite this, there has been little work to establish and quantify the types of
      impacts (both negative and positive) that warfare may have on such systems. This
      paper firstly highlights why rivers and lakes may be susceptible to warfare
      related impacts, before synthesizing the available literature to explore the
      following main themes: intensification of wartime resource acquisition, use of
      water as an offensive or defensive weapon, direct and indirect effects of
      explosive ordnance, increased pollution, introduction of invasive alien species,
      and positive ecological impacts. This is then followed by a discussion of the
      implications of such impacts in relation to future warfare, including a
      consideration of the efficacy of existing legal instruments to protect the
      environment during conflict, and the trend for war to become more localized and
      'informal', and therefore less regulated. Finally, the paper identifies key
      research foci for understanding and mitigating the effects of warfare on
      freshwater ecosystems.

PMID- 21904932
TI  - Enhanced wound healing associated with Sharpey's fiber-like tissue formation
      around FGF-2-apatite composite layers on percutaneous titanium screws in rabbits.
AB  - BACKGROUND: Pin-tract infections are the most common complications of external
      fixation. To solve the problem, we developed a fibroblast growth factor-2 (FGF-2)
      apatite composite layer for coating titanium screws. The purpose of this study
      was to elucidate the mechanism of the improvement in infection resistance
      associated with FGF-2-apatite composite layers. METHOD: We analyzed FGF-2 release
      from the FGF-2-apatite composite layer and the mitogenic activity of the FGF-2
      apatite composite layer. We evaluated time-dependent development of macroscopic
      pin-tract infection around uncoated titanium control screws (n = 10). Screws
      coated with the apatite layer (n = 16) and FGF-2-apatite composite layer (n = 16)
      were percutaneously implanted for 4 weeks in the medial proximal tibia in
      rabbits. RESULTS: A FGF-2-apatite composite layer coated on the screws led to the
      retention of the mitogenic activity of FGF-2. FGF-2 was released from the FGF-2
      apatite composite layer in vitro for at least 4 days, which corresponds to a
      period when 30% of pin-tract infections develop macroscopically in the
      percutaneous implantation of uncoated titanium control screws. The macroscopic
      infection rate increased with time, reaching a plateau of 80-90% within 12 days.
      This value remained unchanged until 4 weeks after implantation. The screws coated
      with an FGF-2-apatite composite layer showed a significantly higher wound healing
      rate than those coated with an apatite layer (31.25 vs. 6.25%, p < 0.05). The
      interfacial soft tissue that bonded to the FGF-2-apatite composite layer is a
      Sharpey's fiber-like tissue, where collagen fibers are inclined at angles from 30
      to 40 degrees  to the screw surface. The Sharpey's Wber-like tissue is rich in
      blood vessels and directly bonds to the FGF-2-apatite composite layer via a thin
      cell monolayer (0.8-1.7 MUm thick). CONCLUSION: It is suggested that the enhanced
      wound healing associated with the formation of Sharpey's fiber-like tissue
      triggered by FGF-2 released from the FGF-2-apatite composite layer leads to the
      reduction in the pin-tract inflammation rate.

PMID- 21904933
TI  - High altitude adaptation in Daghestani populations from the Caucasus.
AB  - We have surveyed 15 high-altitude adaptation candidate genes for signals of
      positive selection in North Caucasian highlanders using targeted re-sequencing. A
      total of 49 unrelated Daghestani from three ethnic groups (Avars, Kubachians, and
      Laks) living in ancient villages located at around 2,000 m above sea level were
      chosen as the study population. Caucasian (Adygei living at sea level, N = 20)
      and CEU (CEPH Utah residents with ancestry from northern and western Europe; N =
      20) were used as controls. Candidate genes were compared with 20 putatively
      neutral control regions resequenced in the same individuals. The regions of
      interest were amplified by long-PCR, pooled according to individual, indexed by
      adding an eight-nucleotide tag, and sequenced using the Illumina GAII platform.
      1,066 SNPs were called using false discovery and false negative thresholds of
      ~6%. The neutral regions provided an empirical null distribution to compare with
      the candidate genes for signals of selection. Two genes stood out. In Laks, a non
      synonymous variant within HIF1A already known to be associated with improvement
      in oxygen metabolism was rediscovered, and in Kubachians a cluster of 13 SNPs
      located in a conserved intronic region within EGLN1 showing high population
      differentiation was found. These variants illustrate both the common pathways of
      adaptation to high altitude in different populations and features specific to the
      Daghestani populations, showing how even a mildly hypoxic environment can lead to
      genetic adaptation.

PMID- 21904934
TI  - Low-molecular-weight methylcellulose-based thermo-reversible gel/pluronic micelle
      combination system for local and sustained docetaxel delivery.
AB  - PURPOSE: To develop low-molecular-weight methylcellulose (LMw MC)-based
      gel/Pluronic F127 micelle combination system for local and sustained delivery of
      docetaxel (DTX). METHODS: LMw MC and Pluronic F127 were used to formulate an
      injectable thermo-reversible gel/micelle combination system containing DTX. The
      DTX-loaded combination system was characterized and its therapeutic efficacy
      evaluated in a subcutaneous tumor model. RESULTS: Mixtures of LMw MC, AS, and
      Pluronic F127 formed gel at ~15-40 degrees C depending on AS concentration. The
      combination system released DTX for >30 days with a biphasic and sustained
      release pattern, and DTX stability was maintained during release. The combination
      system significantly enhanced anti-cancer effects of DTX and prolonged survival
      of the model mouse in comparison with free DTX. CONCLUSIONS: The LMw MC
      gel/Pluronic F127 micelle combination system constitutes a promising tool for
      reducing tumor size and eradicating remaining tumor cells before and after
      surgery.

PMID- 21904935
TI  - Influence of fed-fasted state on intestinal PEPT1 expression and in vivo
      pharmacokinetics of glycylsarcosine in wild-type and Pept1 knockout mice.
AB  - PURPOSE: To determine if fasting would affect the intestinal expression and in
      vivo functional activity of PEPT1 as determined after oral dosing of the
      dipeptide glycylsarcosine (GlySar). METHODS: Systemic exposure and tissue
      distribution studies were performed in wild-type and Pept1 knockout mice, under
      fed and fasted conditions, following both intravenous and oral doses of
      [(14)C]GlySar at 5 nmol/g body weight. Intestinal PEPT1 expression was evaluated
      by real-time PCR and immunoblot analyses. RESULTS: We found that expression of
      PEPT1 protein in the small intestine was increased ~2-fold in wild-type mice
      during fasted as compared to fed conditions. In agreement, systemic exposure and
      peak plasma concentrations of orally administered GlySar were 40 and 65% greater,
      respectively, in wild-type mice during fasted vs. fed state. No significant
      differences were observed between fed and fasted animals during PEPT1 ablation.
      Tissue distribution of GlySar was unchanged after oral dosing for all four
      treatment groups. CONCLUSIONS: As little as 16 h of fasting can cause significant
      upregulation of PEPT1 protein expression in the small intestine, which then
      translates into a significant increase in in vivo oral absorption of GlySar.

PMID- 21904936
TI  - A habituation account of change detection in same/different judgments.
AB  - We investigated the basis of change detection in a short-term priming task. In
      two experiments, participants were asked to indicate whether or not a target word
      was the same as a previously presented cue. Data from an experiment measuring
      magnetoencephalography failed to find different patterns for "same" and
      "different" responses, consistent with the claim that both arise from a common
      neural source, with response magnitude defining the difference between immediate
      novelty versus familiarity. In a behavioral experiment, we tested and confirmed
      the predictions of a habituation account of these judgments by comparing
      conditions in which the target, the cue, or neither was primed by its
      presentation in the previous trial. As predicted, cue-primed trials had faster
      response times, and target-primed trials had slower response times relative to
      the neither-primed baseline. These results were obtained irrespective of response
      repetition and stimulus-response contingencies. The behavioral and brain activity
      data support the view that detection of change drives performance in these tasks
      and that the underlying mechanism is neuronal habituation.

PMID- 21904937
TI  - Snow-shoveling and the risk of acute coronary syndromes.
AB  - BACKGROUND: Snow-shoveling is a necessary activity for those living in temperate
      climates, but there are no large studies identifying a connection between this
      activity and the development of acute coronary syndromes (ACS). OBJECTIVES: The
      aim of this study was to identify potential factors that place individuals at
      higher risk for developing a snow-shoveling-related ACS. METHODS: We performed a
      chart review over two consecutive winter seasons to identify a sample of ACS
      events associated with shoveling snow. Demographics, cardiovascular risk factors
      and medication use of the shoveling-related and non-shoveling-related event
      groups were compared, and multivariate regression was used to identify a subset
      of relevant factors. RESULTS: Our study population included 500 patients with
      ACS, mean age of 65.7 +/- 13.4 years (range 31-94) and 66.7% of the events
      occurred in males. A total of 35 (7%) events were documented to have occurred
      following snow-shoveling. Between patients with snow-shoveling-related and non
      related events there were no significant differences in the prevalence of
      diabetes, hypertension, hypercholesterolemia or sleep apnea. Logistic regression
      did not show any significant group differences in age and known coronary artery
      disease; however, those suffering a snow-shoveling-related event were 3.6 times
      more likely to have a family history of premature cardiovascular disease (p =
      0.001) and were 4.8 times more likely to be male (p = 0.01). CONCLUSION: A family
      history of premature cardiovascular disease and male gender were found to have
      strong, independent associations with having a snow-shoveling-related ACS. A
      history of chronic stable angina trended toward an association.

PMID- 21904938
TI  - Phaseoloidin, a homogentisic acid glucoside from Nicotiana attenuata trichomes,
      contributes to the plant's resistance against lepidopteran herbivores.
AB  - Plant trichomes are known for their capability to produce and store secondary
      metabolites that protect plants from biotic and abiotic stresses. (1)H NMR
      studies on intact individual trichomes located on the leaf surface of Nicotiana
      attenuata revealed the presence of two major secondary metabolites: nicotine, the
      signature metabolite of the genus, and phaseoloidin, a homogentisic acid
      glucoside. This glucoside was reported originally from the seeds of Entada
      phaseoloides, and this is the first report of its occurrence in a Solanaceous
      plant. Artificial diet feeding bioassays with Manduca sexta and Spodoptera
      littoralis larvae, two important herbivores of N. attenuata, revealed that the
      ingestion of phaseoloidin negatively influenced caterpillar performance. This
      effect was more pronounced for the generalist, S. littoralis, than for the
      specialists, M. sexta.

PMID- 21904939
TI  - Susceptibility-weighted imaging: a new tool for detection of intratumoral
      bleeding and subarachnoid hemorrhage--report of two cases.

PMID- 21904940
TI  - Isometric non-machine-based prevention training program: effects on the cross
      sectional area of the paravertebral muscles on magnetic resonance imaging.
AB  - PURPOSE: The purpose of this study was to determine potential effects of
      isometric non-machine-based training on the cross-sectional area (CSA) of the
      paravertebral muscles in volunteers who were participants in a prevention
      program. An increase in the CSA of back muscles after various machine-based
      exercises have been reported but non-machine-based training programs have not
      been adressed before. MATERIALS AND METHODS: In the study 14 volunteers, who were
      participants of a company internal prevention program, underwent a magnetic
      resonance (MR) examination before and after a 3 months training program to
      improve back muscle strength. The MRI protocol consisted of T1-weighted and T2
      weighted images aligned to the intervertebral disc spaces. The CSAs of the
      erector spinae and quadratus lumborum muscles were assessed twice by 2 operators
      at the levels L3/4, L4/5 and L5/S1. RESULTS: Out of 14 subjects 11 completed the
      training. The recorded CSA values exhibited an intrarater and intrarater
      correlation coefficient ranging from 0.949 to 0.989. There was an increase in CSA
      in all subjects after the training period (mean increase 8%). CONCLUSIONS: A 3
      month isometric training program is sufficient to effect measurable increases in
      back muscles volume. The study demonstrated the usefulness of MRI to quantify
      such changes as a measure of training efficacy and compliance into the training
      program. These results represent a rationale for further studies to determine the
      effect of different training methods on the CSA of back muscles and to correlate
      structural changes with clinical symptoms in chronic low back pain syndrome.

PMID- 21904941
TI  - Calcified intracranial masses: an unexpected diagnosis in western radiology.

PMID- 21904942
TI  - Defining cancer survivorship: a more transparent approach is needed.
AB  - INTRODUCTION: There is a lack of a consistent, operational definition of what it
      means to be a cancer survivor despite widespread use of the term. The term
      carries positive connotations of 'beating' cancer, but some people living past
      cancer do not identify with this portrayal. METHODS: The term 'cancer survivor'
      was first developed and used in the USA for advocacy reasons and to promote
      research and care of this growing population. Some organizations define a cancer
      survivor from the time of cancer diagnosis. Researcher and policy makers may use
      different definitions based on their research or funding priorities. RESULTS: The
      use of the term 'cancer survivor', its acceptability and its interpretation
      amongst people living past a cancer diagnosis and primary treatment is relatively
      understudied. There may be numerous interpretations of cancer survivorship
      amongst people living past cancer, and some individuals may not relate to the
      term. DISCUSSION AND IMPLICATIONS FOR CANCER SURVIVORS: Instead of working
      towards a universal definition of cancer survivorship, we suggest that
      researchers and policy makers use operational descriptions when discussing the
      diverse population of people living past a cancer diagnosis.

PMID- 21904943
TI  - Coronal fractures of the medial femoral condyle: a series of 6 cases and review
      of literature.
AB  - Isolated coronal fracture of medial femoral condyle with intact lateral femoral
      condyle is extremely rare. We present our experience with such 6 cases of coronal
      fractures of medial femoral condyle. We reviewed all case records of cases of
      coronal fractures of femoral condyle which presented to our centre from Jan 2000
      to Jun 2009. Of 72 such cases, 56 were of lateral condyle, 9 were bicondylar, and
      7 were only medial femoral condyle fractures. However, one of the 7 cases was a
      skeletally immature child with a physeal injury and hence excluded. All the 6
      patients with medial femoral condyle fractures were retrospectively evaluated
      both clinically and radiologically. Of the 6 patients with medial condyle
      fractures, three patients had an isolated medial femoral condyle fracture, while
      three of them had associated fractures. Four of these patients were identified at
      the initial presentation. However, the fracture was missed during initial
      evaluation in one of the patients, while another patient presented with neglected
      medial Hoffa fracture after 6 months of injury. Mechanism of injury was direct
      impact to the medial side of knee in flexion in 4 out of 6 cases. All cases were
      operated through medial or antero-medial approach, and fixation was achieved in
      all with antero-posterior screws. All cases united at a mean period of 4.6
      months. Coronal fractures of the medial femoral condyle are very rare, and there
      is a highly likelihood of these fractures being missed by an average orthopaedic
      surgeon. A high index of suspicion is necessary for early diagnosis especially in
      cases of undisplaced fractures. Being intra-articular, the ideal management
      includes open reduction and internal fixation. Medial or antero-medial approach
      with antero-posterior screws is the preferred method for fixation.

PMID- 21904944
TI  - Family environment and premarital intercourse in Bandjoun (West Cameroon).
AB  - Family environment is one of the most influential factors on youth sexual
      behavior but has received little investigation in sub-Saharan Africa. Yet, a
      comprehensive understanding of family influences could improve the efficiency of
      reproductive health (RH) interventions. Using retrospective data from a
      population-based survey, life-table analysis was utilized to compute the median
      age at premarital intercourse among 1,182 youth aged 12-24 years. Discrete-time
      hazard models were used in multivariate analysis to estimate the effects of
      family structures and parent-child interactions on premarital intercourse.
      Overall, 42% of participants had a premarital intercourse, and the median age at
      first sex was 16.9 years. Participants in nuclear two-parent families had the
      highest median (17.7) compared with those in nuclear one-(16.7), extended one
      (16.5), extended two-parent families (16.9) or other relatives (16.8). Youth from
      monogamous families had the highest median (16.9) compared to those from
      polygamous (16.3) and other families (16.0). Orphans and youth reporting family
      transitions were more likely to initiate first sex at an earlier age compared
      with non-orphans and non-movers, with a median of 16.1 and 16.9 years,
      respectively. Multivariate results showed that living in extended families, being
      orphaned, and family transitions significantly increased the risk of premarital
      intercourse. Polygamy showed marginal effects. Stronger parent-child
      relationships and higher levels of parental control decreased the risk of
      premarital intercourse. Unexpectedly, parent-child communication was
      significantly associated with a higher risk of sexual debut. Programmatically,
      family environment is an important resource that needs to be promoted when
      designing RH interventions in sub-Saharan Africa.

PMID- 21904945
TI  - Randomized controlled trial of health maintenance reminders provided directly to
      patients through an electronic PHR.
AB  - BACKGROUND: Provider and patient reminders can be effective in increasing rates
      of preventive screenings and vaccinations. However, the effect of patient
      directed electronic reminders is understudied. OBJECTIVE: To determine whether
      providing reminders directly to patients via an electronic Personal Health Record
      (PHR) improved adherence to care recommendations. DESIGN: We conducted a cluster
      randomized trial without blinding from 2005 to 2007 at 11 primary care practices
      in the Partners HealthCare system. PARTICIPANTS: A total of 21,533 patients with
      access to a PHR were invited to the study, and 3,979 (18.5%) consented to enroll.
      INTERVENTIONS: Patients in the intervention arm received health maintenance (HM)
      reminders via a secure PHR "eJournal," which allowed them to review and update HM
      and family history information. Patients in the active control arm received
      access to an eJournal that allowed them to input and review information related
      to medications, allergies and diabetes management. MAIN MEASURES: The primary
      outcome measure was adherence to guideline-based care recommendations. KEY
      RESULTS: Intention-to-treat analysis showed that patients in the intervention arm
      were significantly more likely to receive mammography (48.6% vs 29.5%, p = 0.006)
      and influenza vaccinations (22.0% vs 14.0%, p = 0.018). No significant
      improvement was observed in rates of other screenings. Although Pap smear
      completion rates were higher in the intervention arm (41.0% vs 10.4%, p < 0.001),
      this finding was no longer significant after excluding women's health clinics.
      Additional on-treatment analysis showed significant increases in mammography (p =
      0.019) and influenza vaccination (p = 0.015) for intervention arm patients who
      opened an eJournal compared to control arm patients, but no differences for any
      measure among patients who did not open an eJournal. CONCLUSIONS: Providing
      patients with HM reminders via a PHR may be effective in improving some elements
      of preventive care.

PMID- 21904946
TI  - Redox state-dependent aggregation of mitochondria induced by cytochrome c.
AB  - Cytochrome c is known to play central role in apoptosis. Here, it is shown that
      ferricytochrome c, but not ferrocytochrome c is able to directly induce the
      aggregation of rat liver mitochondria, similar to the effect caused by magnesium
      ions at high concentrations. The aggregation was revealed by a decrease in light
      dispersion of mitochondrial suspension and it was confirmed by the optical
      microscopy. In the medium containing NADH and cytochrome c, mitochondrial
      aggregation was initiated only after exhaustion of NADH leading to oxidation of
      cytochrome c. The aggregation induced by 30 MUM ferricytochrome c, but not by 5
      mM MgCl(2), was completely inhibited by 30-100 MUM ferricyanide, thus indicating
      that ferricyanide-cytochrome c specific interaction prevents mitochondrial
      aggregation. After completion of the aggregation caused by ferricytochrome c,
      this effect cannot be readily reversed by subsequent reduction of cytochrome c.
      The aggregation induced by ferricytochrome c and/or magnesium ions explains
      masking of the external NADH-oxidase activity of mitochondria in vitro reported
      in the literature. This new cytochrome c redox state-dependent phenomenon might
      also be involved in more complex mechanisms controlling aggregation (clustering)
      of mitochondria in vivo under the influence of pro-apoptotic factors and requires
      further study.

PMID- 21904947
TI  - Simvastatin protects osteoblast against H2O2-induced oxidative damage via
      inhibiting the upregulation of Nox4.
AB  - Statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, have been
      used clinically as a cholesterol-lowering drug to treat hyperlipidemia. In recent
      years, accumulating evidence indicates the possible beneficial effect of statins
      on osteoporosis. However, the underlying molecular mechanism remains to be
      elucidated. In the present study, we investigated the therapeutic effects of
      simvastatin on cell viability, apoptosis, and alkaline phosphatase activity in
      murine osteoblastic MC3T3-E1 cells treated by hydrogen peroxide (H(2)O(2), 100
      MUM). It was shown that simvastatin suppressed H(2)O(2)-induced oxidative stress
      and attenuated H(2)O(2)-induced cell injury including increasing osteoblastic
      viability, inhibiting apoptosis, and promoting differentiation. Then, we examined
      the effects of simvastatin (10(-7) M) on Nox1, Nox2, and Nox4 expressions in
      osteoblastic cells treated by H(2)O(2) (100 MUM). We found that in MC3T3-E1
      cells, H(2)O(2)-induced upregulation of Nox4 expression was inhibited by
      simvastatin, which was restored by farnesyl pyrophosphate (5 MUM) as well as
      geranylgeranyl pyrophosphate (5 MUM). RNAi approach was used to reduce Nox4
      protein levels in osteoblastic cells to explore its biological effects against
      H(2)O(2)-induced oxidative damage. When Nox4 expression was reduced in
      osteoblastic cells, H(2)O(2)-induced cell injury was attenuated markedly. We
      concluded that simvastatin protected osteoblast against H(2)O(2)-induced
      oxidative damage, at least in part, via inhibiting the upregulation of Nox4.

PMID- 21904948
TI  - [Disorders of sexual development and identity in childhood and adolescence.
      Expert meeting in Krefeld, 12 February 2011].

PMID- 21904949
TI  - A high-throughput solid phase screening method for identification of
      lignocellulose-degrading bacteria from environmental isolates.
AB  - The development of cost-effective biofuels will require improvements in the
      efficiency of biomass deconstruction, a process typically carried out by
      lignocellulose-degrading enzymes. Environmental microbes represent an abundant
      and diverse source of lignocelluloses-degrading enzymes for use in biotechnology.
      However, identification of microorganisms that possess these enzymes has been
      slowed by a lack of rapid screening methodologies, particularly those that
      utilize native lignocellulosic substrates. In this report, we describe a new,
      solid-phase screening system for the identification of microbes capable of
      lignocellulose degradation. The critical component of this screening system is
      the use of acrylamide, instead of agar, as the solidifying agent. Our results
      show that this screening method allows for the identification of Gram-positive
      and Gram-negative bacteria that possess cellulose and hemicellulose degrading
      activities from environmental isolates.

PMID- 21904950
TI  - Selective serotonin reuptake inhibitor treatment and risk of fractures: a meta
      analysis of cohort and case-control studies.
AB  - Studies on use of selective serotonin reuptake inhibitors (SSRIs) and risk of
      fracture have yielded inconsistent results. This meta-analysis, which pooled
      results from 13 qualifying cohort and case-control studies, found that SSRIs were
      associated with a significantly increased risk of fractures. INTRODUCTION: This
      study was conducted to assess whether people who take SSRIs are at an increased
      risk of fracture. METHODS: We conducted a meta-analysis of observational studies.
      Relevant studies published by February 2010 were identified through literature
      searches using MEDLINE (from 1966), EMBASE (from 1988), PsycINFO (from 1806), and
      manual searching of reference lists. Only cohort or case-control studies that
      examined the association of SSRIs and risk of fracture and bone loss were
      included. Data were abstracted independently by two investigators using a
      standardized protocol; disagreements were resolved by consensus. Random effects
      models were used for pooled analysis due to heterogeneity in the studies.
      RESULTS: Thirteen studies met inclusion criteria. Overall, SSRI use was
      associated with a significantly increased risk of fracture (relative risk, RR,
      1.72; 95% CI [1.51, 1.95]; P < 0.001). An increased fracture risk associated with
      SSRIs also was observed in the three studies that adjusted for bone mineral
      density (RR, 1.70; 95% CI [1.28, 2.25]; P < 0.001) and in the four studies that
      adjusted for depression (RR 1.74; 95% CI [1.28, 2.36]; P < 0.001). SSRI use was
      not associated with bone loss in the two cohort studies of women (P = 0.29). The
      overall association between SSRI use and fracture risk was weaker (RR, 1.40; 95%
      CI [1.22, 1.61]), though still significant (P < 0.001) in analyses that accounted
      for apparent publication bias. CONCLUSIONS: Use of SSRIs is associated with
      increased risk of fracture. The SSRIs may exert an increased risk of fracture
      independent of depression and bone mineral density.

PMID- 21904951
TI  - Rib fracture as a predictor of future fractures in young and older postmenopausal
      women: National Osteoporosis Risk Assessment (NORA).
AB  - A rib fracture history after age 45 was associated with a 5.4-fold increase in
      new rib fracture risk and a 2.4-fold increase in risk of any new clinical
      fracture in 155,031 postmenopausal women. A rib fracture history suggests
      osteoporosis and should be considered when evaluating patients for interventions
      to prevent fractures. INTRODUCTION: Until recently, little attention was paid to
      rib fracture as an osteoporosis marker. Emerging evidence suggests rib fracture
      may be an osteoporotic fracture in men and women. We report the 5-year
      independent association between baseline rib fracture histories and self-reported
      future fractures by age (decade) in the NORA cohort (155,031 postmenopausal
      women, 50-99 years). METHODS: Participants reported fracture history and
      responded to follow-up surveys at years 1, 3, or 6. Women with a baseline rib
      fracture history without other fractures were compared with women with no
      fracture. RESULTS: At baseline, 4,758 (3.07%) women reported a rib fracture
      history without other fractures; 6,300 women reported 6,830 new clinical
      fractures, including wrist (2,271), rib (1,891), spine (1,136), hip (941), and
      forearm (591). Adjusted relative risk (ARR) values (95% confidence interval [CI])
      for future fractures in women with rib fracture history versus women with no
      fracture history were 5.4 (4.8-6.1) at the rib, 2.1 (1.7-2.6) at the spine, and
      1.4 (1.1-1.7) at the wrist, and not significant for forearm or hip fractures.
      Future fracture risk was at least doubled in women with a rib fracture history in
      all ages: ARR (95% CI) 3.4 (2.8-4.0) for ages 50-59, 2.5 (2.1-3.0) for ages 60
      69, 2.0 (1.7-2.3) for ages 70-79, and 2.0 (1.6-2.6) for ages >80. CONCLUSIONS:
      Rib fracture, the second most common clinical fracture in women (after wrist
      fracture), predicted future fractures of the rib, wrist, and spine at all ages.
      Women presenting with rib fractures should be evaluated for appropriate
      management to prevent future fractures.

PMID- 21904952
TI  - An evaluation of peripherally inserted central venous catheters for children with
      cancer requiring long-term venous access.
AB  - Long-term venous access is essential when treating malignant diseases. We
      reviewed our experience with peripherally inserted central venous catheters
      (PICC) in children suffering from various malignancies with regard to catheter
      life, reasons for removal, and complications. Ninety-three PICCs were inserted in
      78 children. Median catheter life was 162 days (range 6-575 days) with a total of
      16,266 catheter days. Seventy-five PICCs (80.6%) had been placed until the
      elective removal or patients' death, whereas 18 PICCs (19.4%) were removed due to
      PICC-related complications; a rate of 1.11 per 1,000 catheter days. Complications
      requiring removal of PICCs included infection (n = 12), occlusion (n = 3),
      dislodgement (n = 2), and phlebitis (n = 1) with rates of 0.74, 0.18, 0.12 and
      0.06 per 1,000 catheter days, respectively. We conclude that PICC provides
      reliable long-term intravenous access in children suffering from malignancies.

PMID- 21904953
TI  - Evaluation of subsidence, chondrocyte survival and graft incorporation following
      autologous osteochondral transplantation.
AB  - PURPOSE: The aim of this study was to evaluate subsidence tendency, surface
      congruency, chondrocyte survival and plug incorporation after osteochondral
      transplantation in an animal model. The potential benefit of precise seating of
      the transplanted osteochondral plug on the recipient subchondral host bone
      ('bottoming') on these parameters was assessed in particular. METHODS: In 18
      goats, two osteochondral autografts were harvested from the trochlea of the
      ipsilateral knee joint and inserted press-fit in a standardized articular
      cartilage defect in the medial femoral condyle. In half of the goats, the
      transplanted plugs were matched exactly to the depth of the recipient hole
      (bottomed plugs; n = 9), whereas in the other half of the goats, a gap of 2 mm
      was left between the plugs and the recipient bottom (unbottomed plugs; n = 9).
      After 6 weeks, all transplants were evaluated on gross morphology, subsidence,
      histology, and chondrocyte vitality. RESULTS: The macroscopic morphology scored
      significantly higher for surface congruency in bottomed plugs as compared to
      unbottomed reconstructions (P = 0.04). However, no differences in histological
      subsidence scoring between bottomed and unbottomed plugs were found. The
      transplanted articular cartilage of both bottomed and unbottomed plugs was vital.
      Only at the edges some matrix destaining, chondrocyte death and cluster formation
      was observed. At the subchondral bone level, active remodeling occurred, whereas
      integration at the cartilaginous surface of the osteochondral plugs failed to
      occur. Subchondral cysts were found in both groups. CONCLUSIONS: In this animal
      model, subsidence tendency was significantly lower after 'bottomed' versus
      'unbottomed' osteochondral transplants on gross appearance, whereas for
      histological scoring no significant differences were encountered. Since the
      clinical outcome may be negatively influenced by subsidence, the use of
      'bottomed' grafts is recommended for osteochondral transplantation in patients.

PMID- 21904954
TI  - Divergences in the response to ultraviolet radiation between polar and non-polar
      ciliated protozoa: UV radiation effects in Euplotes.
AB  - Ultraviolet (UV) radiation has detrimental effects on marine ecosystems, in
      particular in the polar regions where stratospheric ozone reduction causes higher
      levels of solar radiation. We analyzed two polar species of Euplotes, Euplotes
      focardii and Euplotes nobilii, for the sensitivity to UV radiation in comparison
      with two akin species from mid-latitude and tropical waters. Results showed that
      they face UV radiation much more efficiently than the non-polar species by
      adopting alternative strategies that most likely reflect different times of
      colonization of the polar waters. While E. focardii, which is endemic to the
      Antarctic, survives for longer exposed to UV radiation, E. nobilii, which
      inhabits both the Antarctic and Arctic, recovers faster from UV-induced damage.

PMID- 21904955
TI  - Aesthetic concepts, perceptual learning, and linguistic enculturation:
      considerations from Wittgenstein, language, and music.
AB  - Aesthetic non-cognitivists deny that aesthetic statements express genuinely
      aesthetic beliefs and instead hold that they work primarily to express something
      non-cognitive, such as attitudes of approval or disapproval, or desire. Non
      cognitivists deny that aesthetic statements express aesthetic beliefs because
      they deny that there are aesthetic features in the world for aesthetic beliefs to
      represent. Their assumption, shared by scientists and theorists of mind alike,
      was that language-users possess cognitive mechanisms with which to objectively
      grasp abstract rules fixed independently of human responses, and that cognizers
      are thereby capable of grasping rules for the correct application of aesthetic
      concepts without relying on evaluation or enculturation. However, in this article
      I use Wittgenstein's rule-following considerations to argue that psychological
      theories grounded upon this so-called objective model of rule-following fail to
      adequately account for concept acquisition and mastery. I argue that this is
      because linguistic enculturation, and the perceptual learning that's often
      involved, influences and enables the mastery of aesthetic concepts. I argue that
      part of what's involved in speaking aesthetically is to belong to a cultural
      practice of making sense of things aesthetically, and that it's within a socio
      linguistic community, and that community's practices, that such aesthetic sense
      can be made intelligible.

PMID- 21904956
TI  - Time to audit.
AB  - INTRODUCTION: Public and political pressures are increasing on doctors and in
      particular surgeons to demonstrate competence assurance. While surgical audit is
      an integral part of surgical practice, its implementation and delivery at a
      national level in Ireland is poorly developed. Limits to successful audit systems
      relate to lack of funding and administrative support. In Wexford General
      Hospital, we have a comprehensive audit system which is based on the Lothian
      Surgical Audit system. MATERIALS AND METHODS: We wished to analyse the amount of
      time required by the Consultant, NCHDs and clerical staff on one surgical team to
      run a successful audit system. Data were collected over a calendar month. This
      included time spent coding and typing endoscopy procedures, coding and typing
      operative procedures, and typing and signing discharge letters. RESULTS: The
      total amount of time spent to run the audit system for one Consultant surgeon for
      one calendar month was 5,168 min or 86.1 h. Greater than 50% of this time related
      to work performed by administrative staff. Only the intern and administrative
      staff spent more than 5% of their working week attending to work related to the
      audit. CONCLUSIONS: An integrated comprehensive audit system requires a very
      little time input by Consultant surgeons. Greater than 90% of the workload in
      running the audit was performed by the junior house doctors and administrative
      staff. The main financial implications for national audit implementation would
      relate to software and administrative staff recruitment. Implementation of the
      European Working Time Directive in Ireland may limit the time available for
      NCHD's to participate in clinical audit.

PMID- 21904957
TI  - Downregulation of KIF23 suppresses glioma proliferation.
AB  - To identify therapeutic molecular targets for glioma, we performed modified
      serological identification of antigens by recombinant complementary DNA (cDNA)
      expression cloning using sera from a mouse glioma model. Two clones, kinesin
      family member 23 (Kif23) and structural maintenance of chromosomes 4 (Smc4), were
      identified as antigens through immunological reaction with sera from mice
      harboring synergic GL261 mouse glioma and intratumoral inoculation with a mutant
      herpes simplex virus. The human Kif23 homolog KIF23 is a nuclear protein that
      localizes to the interzone of mitotic spindles, acting as a plus-end-directed
      motor enzyme that moves antiparallel microtubules in vitro. Expression analysis
      revealed a higher level of KIF23 expression in glioma tissues than in normal
      brain tissue. The introduction of small interfering RNA (siRNA) targeting KIF23
      into two different glioma cell lines, U87MG and SF126, downregulated KIF23
      expression, which significantly suppressed glioma cell proliferation in vitro.
      KIF23 siRNA-treated glioma cells exhibited larger cell bodies with two or more
      nuclei compared with control cells. In vivo analysis using mouse xenograft showed
      that KIF23 siRNA/DNA chimera-treated tumors were significantly smaller than
      tumors treated with control siRNA/DNA chimera. Taken together, our results
      indicate that downregulation of KIF23 decreases proliferation of glioma cells and
      that KIF23 may be a novel therapeutic target in malignant glioma.

PMID- 21904958
TI  - Inducible expression of neurotrophic factors by mesenchymal progenitor cells
      derived from traumatically injured human muscle.
AB  - Peripheral nerve damage frequently accompanies musculoskeletal trauma and repair
      of these nerves could be enhanced by the targeted application of neurotrophic
      factors (NTFs), which are typically expressed by endogenous cells that support
      nerve regeneration. Injured muscle tissues express NTFs to promote reinnervation
      as the tissue regenerates, but the source of these factors from within the
      muscles is not fully understood. We have previously identified a population of
      mesenchymal progenitor cells (MPCs) in traumatized muscle tissue with properties
      that support tissue regeneration, and our hypothesis was that MPCs also secrete
      the NTFs that are associated with muscle tissue reinnervation. We determined that
      MPCs express genes associated with neurogenic function and measured the protein
      level expression of specific NTFs with known functions to support nerve
      regeneration. We also demonstrated the effectiveness of a neurotrophic induction
      protocol to enhance the expression of the NTFs, which suggests that the
      expression of these factors may be modulated by the cellular environment.
      Finally, neurotrophic induction affected the expression of cell surface markers
      and proliferation rate of the MPCs. Our findings indicate that traumatized muscle
      derived MPCs may be useful as a therapeutic cell type to enhance peripheral nerve
      regeneration following musculoskeletal injury.

PMID- 21904960
TI  - American Society of Breast Surgeons Presidential address: three simple ideas.

PMID- 21904959
TI  - Feasibility of percutaneous excision followed by ablation for local control in
      breast cancer.
AB  - PURPOSE: Percutaneous ablation of breast cancer has shown promise as a treatment
      alternative to open lumpectomy. We hypothesized that percutaneous removal of
      breast cancer followed by percutaneous ablation to sterilize and widen the
      margins would not only provide fresh naive tissue for tumor marker and research
      investigation, but also better achieve negative margins after ablation. METHODS:
      Patients diagnosed by percutaneous biopsy (ultrasound or stereotactic-guided)
      with breast cancer <=1.5 cm, >1 cm from the skin, and <=1 cm residual disease and
      no multicentric disease by magnetic resonance imaging were accrued to this
      institutional review board-approved study. Patients were randomized to laser
      versus radiofrequency ablation. The ultrasound-guided ablation was performed in
      the operating room and followed by immediate excision, whole-mount pathology with
      proliferating cell nuclear antigen staining, and reconstruction. RESULTS: Twenty
      one patients were enrolled onto the study. Fifteen patients received
      radiofrequency ablation, and all showed 100% ablation and negative margins.
      Magnetic resonance imaging was helpful in excluding multicentric disease but less
      so in predicting presence or absence of residual disease. Seven of these patients
      showed no residual tumor and eight showed residual dead tumor (0.5 +/- 0.7 cm,
      range 0.1-2.5 cm) at the biopsy site with clear margins. The laser arm (3
      patients) pathology demonstrated unpredictability of the ablation zone and
      residual live tumor. CONCLUSIONS: This pilot study demonstrates the feasibility
      of a novel approach to minimally invasive therapy: percutaneous excision and
      effective cytoreduction, followed by radiofrequency ablation of margins for the
      treatment of breast cancer. Laser treatment requires further improvement.

PMID- 21904961
TI  - Intact Percutaneous Excision (IPEX) for Definitive Diagnosis of High-Risk Breast
      Lesions.
AB  - BACKGROUND: Open surgical excision (OSE) is generally recommended when image
      guided core needle breast biopsy demonstrates a high-risk lesion (HRL). We
      evaluated intact percutaneous excision (IPEX) with standard radiologic and
      histologic criteria for definitive diagnosis of HRL, particularly atypical ductal
      hyperplasia (ADH).The primary goal was to confirm criteria associated with <2%
      risk for upgrade to carcinoma, equivalent to risk associated with BI-RADS 3
      lesions, for which imaging surveillance is considered sufficient. METHODS: In an
      institutional review board-approved prospective trial, 1,170 patients recommended
      for breast biopsy at 25 institutions received IPEX with a vacuum- and
      radiofrequency-assisted device. ADH patients in whom the imaged lesion had been
      removed and the lesion adequately centered for definitive characterization were
      designated as the potential surgical avoidance population (PSAP) before OSE.
      Subsequent OSE specimen pathology was compared with IPEX findings. RESULTS: In
      1,170 patients, 191 carcinomas and 83 (7%) HRL, including 32 ADH (3%), were
      diagnosed via IPEX. None of the 51 non-ADH HRL were upgraded to carcinoma on OSE
      (n = 24) or, if OSE was declined, on radiologic follow-up (n = 27). No ADH
      lesions meeting PSAP criteria (n = 10) were upgraded to carcinoma on OSE; 3 (14%)
      of 22 non-PSAP ADH lesions were upgraded to carcinoma on OSE. In summary, no
      upgrades to carcinoma were made in patients with non-ADH lesions who underwent
      IPEX or in ADH patients who had IPEX, met histologic and radiologic criteria, and
      underwent OSE. CONCLUSIONS: IPEX combined with straightforward histologic and
      radiologic criteria and imaging surveillance constitutes acceptable management of
      image-detected HRL, including ADH.

PMID- 21904962
TI  - The role of preoperative [18F]fluorodeoxyglucose positron emission tomography in
      predicting early recurrence after curative resection of hepatocellular
      carcinomas.
AB  - PURPOSE: (18)F-fluorodeoxyglucose (FDG) uptake on positron emission tomography
      (PET) scan reflects tumor differentiation and predicts clinical outcome in
      patients with hepatocellular carcinoma (HCC). We investigated the correlation of
      PET scans with tumor differentiation and early tumor recurrence (time-to
      recurrence <1 year). METHODS: We reviewed the medical records of 93 patients with
      HCC who underwent curative resection at our hospital from August 2004 through
      December 2008. PET scans were performed preoperatively, and the maximum
      standardized uptake value of the tumor (SUV(tumor)) and the tumor-to-non-tumor
      SUV ratio (TNR) were calculated from FDG uptake. RESULTS: Twenty-six (27.9%) had
      recurrences and 12 of them (46.2%) had early recurrences. SUV(tumor) and TNR
      correlated strongly with tumor differentiation (p < 0.001). Early recurrence-free
      and the overall survival rates in the low TNR group (TNR <2.0) were higher than
      in the high TNR group (TNR >=2.0) (p = 0.015, p = 0.013). According to univariate
      analysis, predictors of early tumor recurrence were large tumor size (>=5 cm),
      high TNR (>=2), high SUV(tumor) (>=4), and high Edmoson-Steiner grade. However,
      on multivariate analysis, none of the examined factors were statistically
      significant independent predictor. CONCLUSION: PET scans reflect tumor
      differentiation in HCCs. Because high TNR (TNR >=2) and SUV(tumor) (SUV >=4) were
      these cutoff point significant predictors in univariate analysis, future studies
      with more statistical power are needed to assess the significance.

PMID- 21904963
TI  - Management of gastrointestinal leaks after minimally invasive esophagectomy:
      conventional treatments vs. endoscopic stenting.
AB  - INTRODUCTION: Gastrointestinal leak is a dreaded complication after
      esophagectomy. Conventional treatments for leak include conservative therapy,
      surgical reoperation, and even complete gastrointestinal (GI) diversion. The aim
      of this study was to evaluate the impact of endoluminal stenting in the
      management of esophagogastric leak after esophagectomy. METHODS: Data on 18
      (11.3%) of 160 patients who developed postoperative leaks after minimally
      invasive esophagectomy were reviewed. Indications for esophagectomy included
      carcinoma (n = 14), Barrett's with high-grade dysplasia (n = 3), and benign
      stricture (n = 1). Neoadjuvant therapy was used in 57.1% of patients with
      carcinoma. The first nine patients underwent conventional treatments for leak
      whereas the latter nine patients underwent endoscopic esophageal covered stenting
      as primary therapy. There were 5 cervical and 13 intrathoracic anastomotic leaks.
      Main outcome measures included patient characteristics, types of treatment,
      length of hospital stay, morbidity, and mortality. RESULTS: Subjects were 16
      males and 2 females with a mean age of 66 years. In the conventional treatment
      group, leaks were treated with neck drainage (n = 4), GI diversion (n = 2), and
      thoracoscopic drainage with or without repair or T-tube placement (n = 3). In the
      endoscopy group, all leaks were treated with endoscopic covered stenting with or
      without percutaneous drainage (n = 9). Control of leaks occurred in 89% of
      patients in the conventional treatment group vs. 100% of patients in the
      endoscopic stenting group. Three patients in the conventional treatment group
      (33%) required esophageal diversion compared to none of the patients in the
      endoscopy group. The 60-day or in-hospital mortality was 0% for both groups.
      CONCLUSION: In our clinical practice, there has been a shift in the management of
      esophagogastric anastomotic leaks to nonsurgical therapy using endoscopic
      esophageal covered stenting. Endoluminal stenting is a safe and effective
      alternative in the management of GI leaks.

PMID- 21904964
TI  - Intensive versus conventional insulin therapy in nondiabetic patients receiving
      parenteral nutrition after D2 gastrectomy for gastric cancer: a randomized
      controlled trial.
AB  - BACKGROUND: This study was used to compare the effects of intensive insulin
      therapy with conventional insulin therapy on postoperative outcomes among
      nondiabetic patients receiving parenteral nutrition following D2 gastrectomy for
      gastric cancer. METHOD: A total of 248 eligible patients were randomly assigned
      to receive intensive insulin therapy targeting a blood glucose level between 4.4
      and 6.1 mmol/l [intensive group (n = 125)] or conventional insulin therapy
      targeting a blood glucose level less than 11.0 mmol/l [conventional group (n =
      123)] during the postoperative period. RESULTS: Mean blood glucose concentrations
      were lower in the intensive group than in the conventional group. Severe
      hypoglycemia defined as blood glucose <=2.2 mmol/l occurred in eight (6.4%)
      patients in the intensive group vs one (0.8%) patient in the conventional group
      (P = 0.036). One (0.8%) patient died in the intensive group vs two (1.6%)
      patients in the conventional group (P = 0.620). However, intensive insulin
      therapy significantly reduced overall postoperative complications rate (from
      25.2% to 13.6%, P = 0.024). Moreover, both insulin resistance indicated as HOMA
      IR and HLA-DR expression on monocytes were improved in the intensive group.
      CONCLUSIONS: Intensive insulin therapy significantly reduced the postoperative
      short-term morbidity but not mortality among nondiabetic patients receiving
      parenteral nutrition after D2 gastrectomy. The benefits may be due to the
      suppression of insulin resistance and improvement of HLA-DR expression on
      monocytes.

PMID- 21904966
TI  - Relationships between liposome properties, cell membrane binding, intracellular
      processing, and intracellular bioavailability.
AB  - Positive surface charge enhances liposome uptake into cells. Pegylation, used to
      confer stealth properties to enable in vivo applications of cationic liposomes,
      compromises internalization. The goal of this study was to determine the
      quantitative relationships between these two liposome properties (separately and
      jointly), liposomes binding to cell membrane, and the subsequent internalization
      and residence in intracellular space (referred to as intracellular
      bioavailability). The results, obtained in pancreatic Hs-766T cancer cells,
      revealed nonlinear and inter-dependent relationships, as well as substantial
      qualitative and quantitative differences. The proportionality constant K of
      intracellular and membrane-bound liposomes at equilibrium (i.e., I(eq) and B(eq))
      showed a positive triphasic relationship with surface charge and a negative
      biphasic relationship with pegylation. Near-neutral liposomes showed little
      internalization of the membrane-bound moiety, increasing to a constant K value
      for medium charge liposomes (+15 to +35 mV zeta potential), followed by a further
      increase for highly charged liposomes (greater than or equal to +46 mV). The
      decline of pegylation with K value showed a breakpoint at 2%. The negative
      consequences of pegylation (%PEG) were partially offset by increasing charge
      (ZP). The best-fitting regression equations are: B(eq) = -1.36 * %PEG + 0.33 *
      ZP; I(eq) = -1.52 * %PEG + 0.34 * ZP. It suggested that 1% pegylation increase
      can be offset with 4 mV ZP. The differences are such that it may be possible to
      balance these parameters to simultaneously maximize the stealth property and
      intracellular bioavailability of cationic liposomes.

PMID- 21904967
TI  - [Valvular heart disease: anesthesia in non-cardiac surgery].
AB  - The probability of treating patients with valvular heart disease during non
      cardiac surgery increases with the age of the patient. The prevalence of valvular
      heart disease is approximately 2.5% and increases further in the patient group
      aged over 75 years old. Patients with valvular heart disease undergoing non
      cardiac surgery have an increased perioperative cardiovascular risk depending on
      the severity of the disease. Knowledge of the hemodynamic alterations and
      compensation mechanisms which accompany diseases of the valve apparatus is
      essential for a suitable treatment of patients with such pre-existing diseases.
      The most common valvular heart diseases lead to volume (mitral valve
      insufficiency) or pressure load (aortic stenosis) of the left ventricle and in
      the case of mitral stenosis to a pressure load on the left atrium. Depending on
      the underlying disease and the type of surgery planned a corresponding choice of
      anesthesia procedure and medication must be made. In the present review article
      the pathophysiology of the relevant valvular heart diseases and the implications
      for perioperative anesthesia management will be presented. An individually
      tailored extended perioperative monitoring allows hemodynamic alterations to be
      rapidly recognized and adequately treated.

PMID- 21904968
TI  - Clinical features and treatment outcomes of isolated secondary central nervous
      system lymphomas in Miyazaki Prefecture.
AB  - BACKGROUND: Secondary central nervous system lymphoma (SCNSL) without extra
      central nervous system (CNS) involvement is characterized by isolated secondary
      CNS relapse in malignant lymphoma patients. SCNSL is a rare disease, and no
      standard treatment has yet been established. PATIENTS AND METHODS: To elucidate
      the clinical characteristics and outcomes of SCNSL, we retrospectively analyzed
      12 patients (median age 67 years) in Miyazaki prefecture for the last 5 years.
      RESULTS: The initial histological diagnoses of the patients were diffuse large B
      cell lymphoma (DLBCL), mantle-cell lymphoma, and adult T-cell lymphoma in 9, 2,
      and 1 patient, respectively. We focused on analysis of the 9 SCNSL cases
      originating from DLBCL. The locations of CNS relapse were the cerebral
      hemisphere, basal ganglia, and cerebellum in 7, 1, and 1 patient, respectively.
      Three patients were treated with high-dose methotrexate (HD-MTX) therapy; 4 with
      whole-brain radiation therapy (WBRTX); and 1 with both HD-MTX and WBRTX. The
      remaining patients were treated with rituximab. Partial remission was achieved in
      6 out of 9 patients (67%); the other 3 patients (33%) did not respond to therapy.
      Median survival of the 9 patients with CNS relapse was 253 days; 6 of the 9
      patients survived for more than 6 months. As of March 2011, 2 HD-MTX group
      patients but none of the WBRTX group patients were alive. CONCLUSIONS: In this
      retrospective study, 6 of 9 patients with SCNSL originating from DLBCL survived
      for more than 6 months. Both HD-MTX and WBRTX had clinical benefits in the
      treatment of SCNSL.

PMID- 21904969
TI  - Insights into the pH up-shift responsive mechanism of Acidithiobacillus
      ferrooxidans by microarray transcriptome profiling.
AB  - To define the molecular response of Acidithiobacillus ferrooxidans under pH up
      shift, temporal gene expression profiles were examined by using whole-genome DNA
      microarrays for A. ferrooxidans. Approximately 30% of the 3,132 genes represented
      on the microarray were significantly upregulated over a 160-min period, while
      about 14% were significantly downregulated. Our results revealed that A.
      ferrooxidans showed potential self-protection and self-regulation performance in
      response to pH up-shift stress. Many genes involved in regulation of membrane
      components were differentially expressed under the pH up-shift stress. Likewise,
      most of genes involved in phosphate metabolism, sulfur assimilation, and CO(2)
      fixation were obviously induced. Conversely, the transcription of a polyphosphate
      kinase gene (AFE1210) associated with phosphate storage was significantly
      repressed, which probably stemmed from the depletion of polyphosphate. Besides,
      most of the genes involved in hydrogen uptake were significantly induced, whereas
      many genes involved in nitrogen fixation were obviously repressed, which
      suggested that hydrogen uptake and nitrogen fixation could contribute to
      cytoplasmic pH homeostasis.

PMID- 21904970
TI  - Deep brain stimulation of the subthalamic nucleus versus the zona incerta in the
      treatment of essential tremor.
AB  - BACKGROUND: Deep brain stimulation (DBS) is an effective treatment for essential
      tremor (ET). Currently the ventrolateral thalamus is the target of choice, but
      the posterior subthalamic area (PSA), including the caudal zona incerta (cZi),
      has demonstrated promising results, and the subthalamic nucleus (STN) has been
      suggested as a third alternative. The objective of the current study was to
      evaluate the effect of STN DBS in ET and to compare this to cZi DBS. METHODS:
      Four patients with ET were implanted with two ipsilateral electrodes, one in the
      STN and one in the cZi. All contacts were evaluated concerning the acute effect
      on tremor, and the effect of chronic DBS in either target was analyzed. RESULTS:
      STN and cZi both proved to be potent targets for DBS in ET. DBS in the cZi was
      more efficient, since the same degree of tremor reduction could here be achieved
      at lower energy consumption. Three patients became tremor-free in the treated
      hand with either STN or cZi DBS, while the fourth had a minor residual tremor
      after stimulation in either target. CONCLUSION: In this limited material, STN DBS
      was demonstrated to be an efficient treatment for ET, even though cZi DBS was
      more efficient. The STN may be an alternative target in the treatment of ET,
      pending further investigations to decide on the relative merits of the different
      targets.

PMID- 21904971
TI  - [Modern face lift surgery].
AB  - Face lift surgery is generally considered the classical surgical procedure of
      plastic surgery. This is an extensive operation which has undergone a huge
      development since its first implementation more than 100 years ago. What began as
      a simple skin tightening procedure is today a sophisticated and complex technique
      which ideally combines different treatment methods planned with surgical
      precision. This article provides an overview of the history of the procedure to
      the present state of the art concept of pairing biplanar and bivectorial face
      neck lifts with autologous fat transfer and dermabrasion.

PMID- 21904972
TI  - [Upper and lower eyelid blepharoplasty : development of aesthetic periocular
      plastic surgery].
AB  - The article describes the indications and techniques for blepharoplasty of the
      upper and lower eyelids as well as combinations with other eyelid correction
      techniques. Upper eyelid blepharoplasty may include skin excision with orbital
      fat modulation as well as ptosis correction and definition of the superior sulcus
      palpebralis. The main goal of lower lid blepharoplasty is modulation of
      intraseptal fat and also often the treatment of a lower lid laxity by canthopexy.
      It is recommended to avoid excessive skin resection in the lower lid. Furthermore
      techniques to address an ectropium are reviewed and possible complications of
      blepharoplasty are presented.

PMID- 21904973
TI  - [Surgical therapy of gynecomastia].
AB  - Nowadays surgical intervention is an essential part of the treatment of
      idiopathic gynecomastia. Choosing the right method is crucial and is based on the
      current status in the clinical and histological evaluation. Before finalizing the
      process of choosing a specific method a prior interdisciplinary evaluation of the
      patient is necessary to ascertain clear indications for a surgical intervention.
      Liposuction is one of the methods which have become popular in recent years. The
      advantages are the possible combination with traditional techniques, such as
      subcutaneous mastectomy or periareolar mastopexy. The main indication is for
      gynecomastia stage IIa/b and is justifiable due to the reduction in surgical
      complications and scarring. Furthermore this technique provides an excellent
      aesthetical outcome for the patient. A total of 162 patients suffering from
      gynecomastia stages I-III (according to Simon) were surgically treated between
      2000 and 2010 and these cases were retrospectively evaluated. The results showed
      a decline in the use of a T-shaped incision in combination with subcutaneous
      mastectomy with periareolar tightening compared to an increase in the use of
      subcutaneous mastectomy in combination with liposuction. The excised tissue
      should always be sent for histological examination to make sure no malignant
      cells were present.

PMID- 21904974
TI  - [Lower body contouring procedures].
AB  - Indications for most forms of abdominoplasty are slight weight fluctuations or
      pregnancy. The steadily increasing number of patients with greater weight loss as
      well as the growing number of bariatric operations subsequently leads to a
      significant increase in body contouring procedures and places new challenges on
      plastic surgeons. After major weight loss patients present with extremely
      variable deformities in the lower and upper trunk as well as the extremities,
      which have to be treated individually with an appropriate procedure. The
      restoration of the lower trunk presents the first stage of the entire
      reconstruction process. The various modifications of abdominoplasty procedures
      with their various incision patterns and scar courses and the circumferential
      lower trunk dermatolipectomy represent advanced operations for every individual
      case. Plastic surgeons should be fully aware of differences and indications of
      every available procedure in the area of the lower trunk and should have the
      ability to offer the entire repertory for each individual deformity. A high
      postoperative patient satisfaction results from a customized procedure selection,
      the optimal implementation with a correspondingly low rate of complications and
      above-average patient care.

PMID- 21904975
TI  - Adventures and lessons of an American biochemist in China.

PMID- 21904976
TI  - Current understanding of Th2 cell differentiation and function.
AB  - Helper T cell (Th) has been identified as a critical immune cell for regulating
      immune response since 1980s. The type 2 helper Tcell (Th2), characterized by the
      production of interleukin-4 (IL-4), IL-5 and IL-13, plays a critical role in
      immune response against helminths invading cutaneous or mucosal sites. It also
      has a functional role in the pathophysiology of allergic diseases such as asthma
      and allergic diarrhea. Currently, most studies have shed light on Th2 cell
      function and behavior in specific diseases, such as asthma and helminthes
      inflammation, but not on Th2 cell itself and its differentiation. Based on
      different cytokines and specific behavior in recent research, Th2 cell is also
      regarded as new subtypes of T cell, such as IL-9 secreting T cell (Th9) and
      CXCR5(+) T follicular helper cells. Here, we will discuss the latest view of Th2
      cell towards their function and the involvement of Th2 cell in diseases.

PMID- 21904977
TI  - The dual role of ubiquitin-like protein Urm1 as a protein modifier and sulfur
      carrier.
AB  - The ubiquitin-related modifier Urm1 can be covalently conjugated to lysine
      residues of other proteins, such as yeast Ahp1 and human MOCS3, through a
      mechanism involving the E1-like protein Uba4 (MOCS3 in humans). Similar to
      ubiquitination, urmylation requires a thioester intermediate and forms isopeptide
      bonds between Urm1 and its substrates. In addition, the urmylation process can be
      significantly enhanced by oxidative stress. Recent findings have demonstrated
      that Urm1 also acts as a sulfur carrier in the thiolation of eukaryotic tRNA via
      a mechanism that requires the formation of a thiocarboxylated Urm1. This role is
      very similar to that of prokaryotic sulfur carriers such as MoaD and ThiS.
      Evidence strongly supports the hypothesis that Urm1 is the molecular fossil in
      the evolutionary link between prokaryotic sulfur carriers and eukaryotic
      ubiquitin-like proteins. In the present review, we discuss the dual role of Urm1
      in protein and tRNA modification.

PMID- 21904979
TI  - Quantitative proteomics analysis of parthenogenetically induced pluripotent stem
      cells.
AB  - Parthenogenetic embryonic stem (pES) cells isolated from parthenogenetic
      activation of oocytes and embryos, also called parthenogenetically induced
      pluripotent stem cells, exhibit pluripotency evidenced by both in vitro and in
      vivo differentiation potential. Differential proteomic analysis was performed
      using differential in-gel electrophoresis and isotope-coded affinity tag-based
      quantitative proteomics to investigate the molecular mechanisms underlying the
      developmental pluripotency of pES cells and to compare the protein expression of
      pES cells generated from either the in vivo-matured ovulated (IVO) oocytes or
      from the in vitro-matured (IVM) oocytes with that of fertilized embryonic stem
      (fES) cells derived from fertilized embryos. A total of 76 proteins were
      upregulated and 16 proteins were downregulated in the IVM pES cells, whereas 91
      proteins were upregulated and 9 were downregulated in the IVO pES cells based on
      a minimal 1.5-fold change as the cutoff value. No distinct pathways were found in
      the differentially expressed proteins except for those involved in metabolism and
      physiological processes. Notably, no differences were found in the protein
      expression of imprinted genes between the pES and fES cells, suggesting that
      genomic imprinting can be corrected in the pES cells at least at the early
      passages. The germline competent IVM pES cells may be applicable for germ cell
      renewal in aging ovaries if oocytes are retrieved at a younger age.

PMID- 21904980
TI  - Dscam mutation leads to hydrocephalus and decreased motor function.
AB  - The nervous system is one of the most complicated organ systems in invertebrates
      and vertebrates. Down syndrome cell adhesion molecule (DSCAM) of the
      immunoglobulin (Ig) superfamily is expressed widely in the nervous system during
      embryonic development. Previous studies in Drosophila suggest that Dscam plays
      important roles in neural development including axon branching, dendritic tiling
      and cell spacing. However, the function of the mammalian DSCAM gene in the
      formation of the nervous system remains unclear. Here, we show that Dscam ( del17
      ) mutant mice exhibit severe hydrocephalus, decreased motor function and impaired
      motor learning ability. Our data indicate that the mammalian DSCAM gene is
      critical for the formation of the central nervous system.

PMID- 21904978
TI  - The network of cytokines, receptors and transcription factors governing the
      development of dendritic cell subsets.
AB  - The pathways leading to the development of different dendritic cell (DC) subsets
      have long been unclear. In recent years, a number of precursors on the route to
      DC development, both under steady state and inflammatory conditions, have been
      described, and the nature of these pathways is becoming clearer. In addition, the
      development of various knockout mouse models and an in vitro system modelling DC
      development have revealed the role of numerous cytokines and transcription
      factors that influence DC development. Here, we review recent findings on the
      factors important in DC development in the context of the developmental pathways
      that have been described.

PMID- 21904981
TI  - Chain length-dependent cooperativity in fatty acid binding and oxidation by
      cytochrome P450BM3 (CYP102A1).
AB  - Fatty acid binding and oxidation kinetics for wild type P450(BM3) (CYP102A1) from
      Bacillus megaterium have been found to display chain length-dependent homotropic
      behavior. Laurate and 13-methyl-myristate display Michaelis-Menten behavior while
      there are slight deviations with myristate at low ionic strengths. Palmitate
      shows Michaelis-Menten kinetics and hyperbolic binding behavior in 100 mmol/L
      phosphate, pH 7.4, but sigmoidal kinetics (with an apparent intercept) in low
      ionic strength buffers and at physiological phosphate concentrations. In low
      ionic strength buffers both the heme domain and the full-length enzyme show
      complex palmitate binding behavior that indicates a minimum of four fatty acid
      binding sites, with high cooperativity for the binding of the fourth palmitate
      molecule, and the full-length enzyme showing tighter palmitate binding than the
      heme domain. The first flavin-to-heme electron transfer is faster for laurate,
      myristate and palmitate in 100 mmol/L phosphate than in 50 mmol/L Tris (pH 7.4),
      yet each substrate induces similar high-spin heme content. For palmitate in low
      phosphate buffer concentrations, the rate constant of the first electron transfer
      is much larger than k (cat). The results suggest that phosphate has a specific
      effect in promoting the first electron transfer step, and that P450(BM3) could
      modulate Bacillus membrane morphology and fluidity via palmitate oxidation in
      response to the external phosphate concentration.

PMID- 21904982
TI  - C-reactive protein functions as a negative regulator of macrophage activation
      induced by apoptotic DNA.
AB  - C-reactive protein (CRP), an acute-phase protein with an ability to bind to
      nuclear antigen, has been reported to regulate cytokine secretion and modulate
      immune responses. We previously reported that activated syngeneic lymphocyte
      derived apoptotic DNA (apopDNA) could induce macrophage activation and contribute
      to the initiation and progression of lupus nephritis. It is reasonable to
      hypothesize that CRP might regulate apopDNA-induced macrophage activation.
      Herein, CRP was shown to promote macrophage-mediated apopDNA uptake by binding to
      apopDNA (CRP/apopDNA complex). Notably, CRP/apopDNA treatment inhibited the
      production of inflammatory cytokines and chemokines by macrophages which could be
      induced by apopDNA alone. Further coculture and transwell studies revealed that
      CRP/apopDNA-induced macrophages prohibited apopDNA-induced macrophage activation
      in an IL-10 dependent manner. These results provide insight into the potential
      mechanism of CRP regulatory activity in macrophage activation induced by apopDNA
      in the context of lupus nephritis and other autoimmune diseases.

PMID- 21904984
TI  - Recent advances in microparticle and nanoparticle delivery vehicles for mucosal
      vaccination.
AB  - The great potential of mucosal vaccination is widely accepted but progress in the
      clinical development of subunit mucosal vaccines has been disappointing. Of the
      available approaches, the use of polymer-based microparticles is attractive
      because these delivery vehicles can be specifically tailored for vaccines and
      they offer the potential for integration of adjuvant. Here we address recent
      developments in the use of particulates as mucosal vaccines and the potential of
      novel targeting strategies, formulation approaches and adjuvant combinations to
      enhance the efficacy of particle-based mucosal vaccines. This review discusses
      the current status of mucosal vaccines based on particles and highlights several
      of the strategies that are currently under investigation for improving their
      immunogenicity. These include enhancing the stability of formulations in the
      luminal environment, increasing uptake by specifically targeting particles to
      mucosal inductive sites, and augmenting immunogenicity through co-formulation
      with immunostimulatory agents.

PMID- 21904983
TI  - Driving efficiency in a high-throughput metabolic stability assay through a
      generic high-resolution accurate mass method and automated data mining.
AB  - Improving analytical throughput is the focus of many quantitative workflows being
      developed for early drug discovery. For drug candidate screening, it is common
      practice to use ultra-high performance liquid chromatography (U-HPLC) coupled
      with triple quadrupole mass spectrometry. This approach certainly results in
      short analytical run time; however, in assessing the true throughput, all aspects
      of the workflow needs to be considered, including instrument optimization and the
      necessity to re-run samples when information is missed. Here we describe a high
      throughput metabolic stability assay with a simplified instrument set-up which
      significantly improves the overall assay efficiency. In addition, as the data is
      acquired in a non-biased manner, high information content of both the parent
      compound and metabolites is gathered at the same time to facilitate the decision
      of which compounds to proceed through the drug discovery pipeline.

PMID- 21904985
TI  - Blood pressure targets for patients with diabetes or kidney disease.
AB  - The most recent scientific guideline statements from foundations and societies
      dealing with diabetes and kidney disease argue for blood pressure (BP) goals
      lower than 130/80 mm Hg, but whether the evidence from properly done clinical
      trials supports this BP level remains questionable. A review of all the evidence
      suggests that almost all of the data come from retrospective data analyses of
      randomized cardiovascular and chronic kidney disease (CKD) trials. Meta-analyses
      of all clinical trials to date demonstrate that reducing BP reduces risk for
      stroke and coronary heart disease, but none have achieved a mean BP goal of less
      than 130/80 mm Hg. In fact, only two prospective trials achieved a BP lower than
      130/80 mm Hg in people with type 2 diabetes, as did three trials in advanced
      proteinuric CKD. Of these, one of the two diabetes trials showed a benefit for
      overall cardiovascular risk reduction, and two of the three kidney disease trials
      showed a benefit on slowing of advanced CKD. Of note, however, these two trials
      in CKD had baseline average proteinuria rates of more than 500 mg/day. No benefit
      of a lower BP was seen in microalbuminuric CKD. Therefore, the totality of the
      prospective randomized trial evidence indicates that a BP less than 130/80 mm Hg
      is not defensible to slow nephropathy progression unless proteinuria levels are
      at least 500 mg/day, and it does not reduce overall cardiovascular events in
      diabetes. Stroke benefit was uniformly seen at BP levels less than 130/80 mm Hg,
      however. Therefore, newer guidelines are emerging that state that the BP goal for
      most people is lower than 140/90 mm Hg with level IA or IB evidence, and that
      levels lower than 130/80 mm Hg are defensible only if advanced proteinuric CKD is
      present or stroke risk is very high (i.e., history of prior stroke or several
      risk factors for stroke, including hypertension, smoking, diabetes mellitus,
      dyslipidemia).

PMID- 21904986
TI  - Backbone resonances assignment of 19 kDa CD1 domain of human mitotic checkpoint
      serine/threonine-protein kinase, Bub1.
AB  - Bub1 is an evolutionarily conserved mitotic checkpoint control protein that is
      present in diverse organisms including yeast and humans. Bub1 is a
      serine/threonine protein kinase and is required for recruitment of Mad1, Mad2,
      Bub3, and CENP-E to kinetochores (Sharp-Baker and Chen in J Cell Biol 153:1239
      1250, 2001). The evolutionarily conserved amino acid region in the N-terminus has
      been called as the CD1 domain. To clarify the action mechanism of Bub1 in
      controlling check point signals, we initiated an NMR structure determination of
      the Bub1 CD1 domain. Here, we report the sequence-specific backbone resonance
      assignments of CD1 domain of human Bub1 (hBub1CD1).

PMID- 21904987
TI  - Abstracts of the 40th Annual Meeting of the European Histamine Research Society.
      May 11-14, 2011. Sochi, Russia.

PMID- 21904988
TI  - Re: Value of diagnostic and therapeutic laparoscopy for abdominal stab wounds.

PMID- 21904989
TI  - Comparison between laparoscopy and noninvasive tests for the diagnosis of
      tuberculous peritonitis.

PMID- 21904990
TI  - Slit versus non-slit mesh placement in total extraperitoneal inguinal hernia
      repair.

PMID- 21904991
TI  - Signal-inducing bone cements for MRI-guided spinal cementoplasty: evaluation of
      contrast-agent-based polymethylmethacrylate cements.
AB  - OBJECTIVE: The purpose of this work is to evaluate two signal-inducing bone
      cements for MRI-guided spinal cementoplasty. MATERIALS AND METHODS: The bone
      cements were made of polymethylmethacrylate (PMMA, 5 ml monomeric, 12 g
      polymeric) and gadoterate meglumine as a contrast agent (CA, 0-40 MUl) with
      either saline solution (NaCl, 2-4 ml) or hydroxyapatite bone substitute (HA, 2-4
      ml). The cement's signal was assessed in an open 1-Tesla MR scanner, with T1W TSE
      and fast interventional T1W TSE pulse sequences, and the ideal amount of each
      component was determined. The compressive and bending strength for different
      amounts of NaCl and HA were evaluated. RESULTS: The cement's MRI signal depended
      on the concentration of CA, the amount of NaCl or HA, and the pulse sequence. The
      signal peaks were recorded between 1 and 10 MUl CA per ml NaCl or HA, and were
      higher in fast T1W TSE than in T1W TSE images. The NaCl-PMMA-CA cements had a
      greater MRI signal intensity and compressive strength; the HA-PMMA-CA cements had
      a superior bending strength. CONCLUSIONS: Concerning the MR signal and
      biomechanical properties, these cements would permit MRI-guided cementoplasty.
      Due to its higher signal and greater compressive strength, the NaCl-PMMA-CA
      compound appears to be superior to the HA-PMMA-CA compound.

PMID- 21904992
TI  - Diet and cancer.
AB  - Large claims have been made for the effectiveness of particular diets in
      preventing cancer or inhibiting its progression. However, more recent clinical
      studies have not confirmed this. Instead it seems that rather than specific
      dietary constituents, total calories influence cancer incidence and progression.
      In this review article, we summarise and interpret the available evidence for
      links between diet and cancer.

PMID- 21904993
TI  - The role of fabricated chimeric free flaps in reconstruction of devastating hand
      and forearm injuries.
AB  - Devastating hand and forearm injuries almost exclusively need free flap transfer
      if reconstruction is attempted. Early active and passive motion is only possible
      with aggressive, early, and comprehensive reconstruction. Despite recent advances
      in compound flaps, in selected cases it might be wise to harvest several smaller
      flaps and microsurgically combine them to one "chain-linked" flap "system." Four
      microsurgically fabricated chimeric free flaps were used in four patients for
      complex hand and forearm injuries. The combinations were sensate anterolateral
      thigh (ALT) flap plus sensate extended lateral arm flap (2x), ALT plus free
      fibula, and ALT plus functional musculocutaneous gracilis muscle. All flaps
      survived completely. Functional rehabilitation was possible immediately after
      flap transfer. There were no donor-site complications except two widened scars.
      The microsurgical fabrication of chimeric free flaps, as well established in head
      and neck reconstruction, can be successfully adapted to massive hand injuries as
      well. Individual placement of selected tissue components, early comprehensive
      reconstruction, and reduction of the number of operations are beneficial in cases
      that need more than one free flap.

PMID- 21904994
TI  - Inadvertent injury of critical perforator vessels during perforator flap surgery.
AB  - Despite the widespread use of perforator flaps, little has been reported about
      the inadvertent injury of perforator vessels. We report a retrospective study of
      the inadvertent injury of perforator vessels. From 1992 through 2010, we
      transferred 467 free perforator flaps (314 anterolateral thigh [ALT] flaps, 99
      fibula osteocutaneous flaps, 46 deep inferior epigastric perforator [DIEP] flaps,
      and 8 other flaps). Inadvertent injury of perforator vessels occurred in seven
      patients. The overall incidence was 1.5%. The rate of the injury was 0.95% with
      ALT flaps, 2.0% with fibula osteocutaneous flaps, and 4.3% with DIEP flaps. Of
      seven, six flaps were salvaged through anastomosis of the injured perforator
      vessels. Perforator injuries resulted more often from mishandling of perforator
      vessels than from dissection technique. Anastomosis of injured perforators is a
      practical salvage procedure that requires high microsurgical skill.

PMID- 21904995
TI  - [Joint replacement: how to lower re-surgery rates].

PMID- 21904996
TI  - Association between cam-type deformities and magnetic resonance imaging-detected
      structural hip damage: a cross-sectional study in young men.
AB  - OBJECTIVE: Femoroacetabular impingement may be a risk factor for hip
      osteoarthritis in men. An underlying hip deformity of the cam type is common in
      asymptomatic men with nondysplastic hips. This study was undertaken to examine
      whether hip deformities of the cam type are associated with signs of hip
      abnormality, including labral lesions and articular cartilage damage, detectable
      on magnetic resonance imaging (MRI). METHODS: In this cross-sectional, population
      based study in asymptomatic young men, 1,080 subjects underwent clinical
      examination and completed a self-report questionnaire. Of these subjects, 244
      asymptomatic men with a mean age of 19.9 years underwent MRI. All MRIs were read
      for cam-type deformities, labral lesions, cartilage thickness, and impingement
      pits. The relationship between cam-type deformities and signs of joint damage
      were examined using logistic regression models adjusted for age and body mass
      index. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined.
      RESULTS: Sixty-seven definite cam-type deformities were detected. These
      deformities were associated with labral lesions (adjusted OR 2.77 [95% CI 1.31,
      5.87]), impingement pits (adjusted OR 2.9 [95% CI 1.43, 5.93]), and labral
      deformities (adjusted OR 2.45 [95% CI 1.06, 5.66]). The adjusted mean difference
      in combined anterosuperior femoral and acetabular cartilage thickness was -0.19
      mm (95% CI -0.41, 0.02) lower in those with cam-type deformities compared to
      those without. CONCLUSION: Our findings indicate that the presence of a cam-type
      deformity is associated with MRI-detected hip damage in asymptomatic young men.

PMID- 21904997
TI  - Reversal of serologic, immunologic, and histologic dysfunction in mice with
      systemic lupus erythematosus by long-term serial adipose tissue-derived
      mesenchymal stem cell transplantation.
AB  - OBJECTIVE: To investigate the efficacy of human adipose tissue-derived
      mesenchymal stem cell (AD-MSC) transplantation in systemic lupus erythematosus
      (SLE) and to determine the optimal transplantation window for stem cells either
      before or after disease onset. METHODS: (NZB*NZW)F1 mice with SLE were
      administered human AD-MSCs (5*10(5)) intravenously every 2 weeks from age 6 weeks
      until age 60 weeks, while the control group received saline vehicle on the same
      schedule. Another experiment was carried out with a different initiation time
      point for serial transplantation (age 6 weeks or age 32 weeks). RESULTS: Long
      term serial administration (total of 28 times) of human AD-MSCs ameliorated SLE
      without any adverse effects. Compared with the control group, the human AD-MSC
      treated group had a significantly higher survival rate with improvement of
      histologic and serologic abnormalities and immunologic function, and also had a
      decreased incidence of proteinuria. Anti-double-stranded DNA antibodies and blood
      urea nitrogen levels decreased significantly with transplantation of human AD
      MSCs, and serum levels of granulocyte-macrophage colony-stimulating factor,
      interleukin-4 (IL-4), and IL-10 increased significantly. A significant increase
      in the proportion of CD4+FoxP3+ cells and a marked restoration of capacity for
      cytokine production were observed in spleens from the human AD-MSC-treated group.
      In the second experiment, an early stage treatment group showed better results
      (higher survival rates and lower incidence of proteinuria) than an advanced stage
      treatment group. CONCLUSION: Serial human AD-MSC transplantation had beneficial
      effects in the treatment of SLE, without adverse effects. Transplantation of
      human AD-MSCs before disease onset was preferable for amelioration of SLE and
      restoration of immune homeostasis.

PMID- 21904998
TI  - Power Doppler ultrasound, but not low-field magnetic resonance imaging, predicts
      relapse and radiographic disease progression in rheumatoid arthritis patients
      with low levels of disease activity.
AB  - OBJECTIVE: Subclinical inflammation and radiographic progression have been
      described in rheumatoid arthritis (RA) patients whose disease is in remission or
      is showing a low level of activity. The aim of this study was to compare the
      ability of ultrasonography and magnetic resonance imaging (MRI) to predict
      relapse and radiographic progression in these patients. METHODS: Patients with RA
      of short or intermediate duration that was either in remission or exhibiting low
      levels of activity according to the Disease Activity Score (DAS) were included in
      the study. Over a period of 1 year, patients underwent clinical and biologic
      assessments every 3 months and radiographic assessments at baseline and 12
      months. Radiographs were graded according to the modified Sharp/van der Heijde
      score (SHS). At baseline, patients underwent ultrasonography and MRI, which were
      graded using binary and semiquantitative scoring systems. Relapse was defined as
      a DAS of >=2.4, and radiographic progression was defined as an increase in the
      SHS of >=1. We tested the association of values by multivariate logistic
      regression. RESULTS: A total of 85 RA patients with a mean disease duration of
      35.3 months were studied. RA was in remission in 47 of these patients, and 38 had
      low levels of disease activity. At 1 year, 26 of the 85 patients (30.6%) showed
      disease relapse, and 9 of the 85 patients (10.6%) showed radiographic
      progression. The baseline PD synovitis count (i.e., the number of joints at
      baseline for which the power Doppler [PD] signal indicated synovitis) predicted
      relapse (adjusted odds ratio [OR] 6.3; 95% confidence interval [95% CI] 2.0
      20.3), and the baseline PD synovitis grade predicted disease progression
      (adjusted OR 1.4 [95% CI 1.1-1.9]). MRI was not predictive of outcomes.
      CONCLUSION: For RA patients whose disease is in remission or who have low levels
      of disease activity, PD signals on ultrasonography could predict relapse or
      radiographic progression and identify those whose disease is adequately
      controlled, which is especially helpful when considering treatment tapering or
      interruption.

PMID- 21904999
TI  - Mucosal-associated invariant T cells promote inflammation and exacerbate disease
      in murine models of arthritis.
AB  - OBJECTIVE: The function of mucosal-associated invariant T (MAIT) cells remains
      largely unknown. We previously reported an immunoregulatory role of MAIT cells in
      an animal model of multiple sclerosis. The aim of this study was to use animal
      models to determine whether MAIT cells are involved in the pathogenesis of
      arthritis. METHODS: MR1-/- and MR1+/+ DBA/1J mice were immunized with bovine type
      II collagen (CII) in complete Freund's adjuvant to trigger collagen-induced
      arthritis (CIA). To assess CII-specific T cell recall responses, lymph node cells
      from mice with CIA were challenged with CII ex vivo, and cytokine production and
      proliferation were evaluated. Serum levels of CII-specific antibodies were
      measured by enzyme-linked immunosorbent assay. Collagen antibody-induced
      arthritis (CAIA) was induced in MR1-/- and MR1+/+ C57BL/6 mice by injection of
      anti-CII antibodies followed by injection of lipopolysaccharide. To demonstrate
      the involvement of MAIT cells in arthritis, we induced CAIA in MR1-/- C57BL/6
      mice that had been reconstituted with adoptively transferred MAIT cells. MAIT
      cell activation in response to cytokine stimulation was investigated. RESULTS:
      The severity of CIA was reduced in MR1-/- DBA/1J mice. However, T and B cell
      responses to CII were comparable in MR1-/- and MR1+/+ DBA/1J mice. MR1-/- C57BL/6
      mice were less susceptible to CAIA, and reconstitution with MAIT cells induced
      severe arthritis in MR1-/- C57BL/6 mice, demonstrating an effector role of MAIT
      cells in arthritis. MAIT cells became activated upon stimulation with interleukin
      23 (IL-23) or IL-1beta in the absence of T cell receptor stimuli. CONCLUSION:
      These results indicate that MAIT cells exacerbate arthritis by enhancing the
      inflammation.

PMID- 21905001
TI  - Safety and efficacy of ocrelizumab in patients with rheumatoid arthritis and an
      inadequate response to methotrexate: results of a forty-eight-week randomized,
      double-blind, placebo-controlled, parallel-group phase III trial.
AB  - OBJECTIVE: To evaluate the efficacy and safety of treatment with ocrelizumab plus
      methotrexate (MTX) in patients with active rheumatoid arthritis (RA) and an
      inadequate response to MTX. METHODS: STAGE was a phase III randomized, double
      blind, parallel-group international study to evaluate the safety and efficacy of
      ocrelizumab compared with placebo in patients with active RA continuing MTX
      treatment. Patients receiving stable doses of MTX were randomized to receive 2
      infusions of placebo (n = 320), ocrelizumab 200 mg (n = 343), or ocrelizumab 500
      mg (n = 343) on days 1 and 15 as well as weeks 24 and 26. Coprimary end points
      were the proportion of patients with an American College of Rheumatology 20%
      improvement criteria (ACR20) response at weeks 24 and 48. Secondary end points
      included the change from baseline in the modified Sharp/van der Heijde score
      (SHS) and the ACR50/70 responses. RESULTS: The ACR20 response rates were 35.7% in
      the placebo group, 56.9% in the ocrelizumab 200 mg group, and 54.5% in the
      ocrelizumab 500 mg group at 24 weeks, and 27.6%, 58.3%, and 62.1%, respectively,
      at 48 weeks (P < 0.0001 versus placebo for each dose at both time points). At
      week 48, both of the ocrelizumab doses improved the ACR50 and ACR70 response
      rates 3-fold as compared with placebo and showed a statistically significant (P <
      0.0001) reduction in joint damage progression relative to placebo (mean change in
      SHS reduced by 85% and 100% for the 200-mg and 500-mg doses, respectively). Rates
      of serious infection were comparable in the placebo (3.48 per 100 patient-years)
      and ocrelizumab 200 mg (3.54 per 100 patient-years) groups but were elevated in
      the ocrelizumab 500 mg group (8.66 per 100 patient-years). CONCLUSION: With both
      ocrelizumab doses, the primary end point was met, and the signs and symptoms of
      RA were significantly improved at weeks 24 and 48. Ocrelizumab also significantly
      inhibited the progression of joint damage. A higher rate of serious infections
      was observed with 500 mg of ocrelizumab as compared with ocrelizumab 200 mg or
      placebo.

PMID- 21905000
TI  - Disruption of vascular homeostasis in patients with Kawasaki disease: involvement
      of vascular endothelial growth factor and angiopoietins.
AB  - OBJECTIVE: In Kawasaki disease (KD), a pediatric vasculitis of medium-sized
      arteries, the coronary arteries are most commonly affected. Angiopoietins and
      vascular endothelial growth factor (VEGF) play an important role in maintaining
      vascular homeostasis. Recently, we identified ANGPT1 and VEGFA as susceptibility
      loci for KD. This study was undertaken to fine-map these associations and to gain
      further insight into their role in this vasculitis of unknown etiology to further
      the search for improved diagnostic and therapeutic options. METHODS: A total of
      292 single-nucleotide polymorphisms (SNPs) located in VEGF and ANGPT and their
      receptors were genotyped in 574 families, including 462 trios. For replication,
      123 cases and 171 controls were genotyped. RESULTS: A significant association
      with KD susceptibility was observed with 5 SNPs in the ANGPT1 gene (most
      significantly associated SNP +265037 C>T; Pcombined=2.3*10(-7) ) and 2 SNPs in
      VEGFA (most significantly associated SNP rs3025039; Pcombined=2.5*10(-4) ). Both
      ANGPT1 +265037 C>T and VEGFA rs3025039 are located in 3' regulatory regions at
      putative transcription factor binding sites. We observed significantly down
      regulated transcript levels of angiopoietin 1 (Ang-1) in patients with acute KD
      compared to patients with convalescent KD. In patients with acute KD, high serum
      protein levels of VEGF and Ang-2 were observed compared to patients with
      convalescent KD and to both controls with and controls without fever.
      Immunohistochemistry demonstrated VEGF and angiopoietin expression in the
      coronary artery wall in autopsy tissue. CONCLUSION: Our data support the
      hypothesis that dysregulation of VEGF and angiopoietins contributes to the
      disruption of vascular homeostasis in KD.

PMID- 21905003
TI  - Ultrasonographic evaluation of medial radial displacement of the medial meniscus
      in knee osteoarthritis.
AB  - OBJECTIVE: To evaluate medial radial displacement (MRD) of the medial meniscus in
      osteoarthritic (OA) and normal knees, with and without weight bearing, using
      ultrasonography (US), and to prospectively evaluate the time course of changes in
      MRD in OA knees. METHODS: The study subjects were 78 patients with OA of the knee
      (69% female; mean age 66.4 years) and 20 healthy, asymptomatic subjects (70%
      female; mean age 64.5 years) who served as a control group. The OA stage was
      determined according to the Kellgren/Lawrence (K/L) radiographic grading system.
      US measurement of MRD was performed with subjects in the supine and standing
      positions. With the exception of subjects who dropped out, 58 OA knees (followup
      rate 74%) were evaluated at baseline and ~1 year later. RESULTS: The medial
      meniscus was significantly displaced radially by weight bearing in control knees
      (P<0.001) and in knees with K/L grades 1-3 OA (P<0.01 for each comparison). MRD
      in either the supine or the standing position was not significantly different
      between the control knees and the K/L grade 1 knees, but significant differences
      were noted between the control knees and K/L grade 2 or more severe OA knees
      (P<0.01 for each comparison). MRD of the medial meniscus had increased
      significantly on followup in all knees (P<0.05 for each comparison) excluding K/L
      grade 4 knees in the standing position. CONCLUSION: MRD of the medial meniscus
      increased with weight bearing and during followup. These findings suggest a close
      association between extraarticular displacement of the medial meniscus and
      progression of OA.

PMID- 21905002
TI  - Gene-gene interaction of BLK, TNFSF4, TRAF1, TNFAIP3, and REL in systemic lupus
      erythematosus.
AB  - OBJECTIVE: Although the number of convincingly established genetic associations
      with systemic lupus erythematosus (SLE) has increased sharply over the last few
      years, refinement of these associations is required, and their potential roles in
      gene-gene interactions need to be further investigated. Recent genome-wide
      association studies (GWAS) in SLE have produced renewed interest in B cell/T cell
      responses and the NF-kappaB signaling pathway. The aim of this study was to
      search for possible gene-gene interactions based on identified single-nucleotide
      polymorphisms (SNPs), in using an approach based on the role of signaling
      pathways. METHODS: The SNPs in BLK, TNFSF4, TRAF1, TNFAIP3, and REL were
      replicated in order to evaluate genetic associations with SLE. TaqMan genotyping
      was conducted in 804 Chinese patients with SLE and 722 matched control subjects.
      A multiple logistic regression model was used to estimate the multiplicative
      interaction effect of the SNPs, and additive interactions were analyzed by 2*2
      factorial designs. Data from a previously published GWAS conducted by the
      International Consortium on the Genetics of Systemic Lupus Erythematosus were
      derived for comparison and validation. RESULTS: Single-marker analysis validated
      the association of BLK rs2736340 (P=4.25*10(-6)) as well as TNFSF4 rs2205960
      (P=2.82*10(-5)) and TNFAIP3 rs5029939 (P=1.92*10(-3)) with SLE susceptibility in
      Chinese. Multiplicative interaction analysis indicated that BLK had an
      interactive effect with TNFSF4 in Chinese patients with SLE (P=6.57*10(-4)).
      Additive interaction analysis revealed interactions between TRAF1 and TNFAIP3 in
      both Chinese (P=2.18*10(-3)) and Caucasians (P=2.86*10(-4)). In addition,
      multiple tendencies toward interactions were observed, and an additive effect was
      observed as the number of risk genotypes increased. CONCLUSION: The results of
      this study provide evidence of the possible gene-gene interactions of BLK,
      TNFSF4, TRAF1, TNFAIP3, and REL in SLE, which may represent a synergic effect of
      T cells and B cells through the NF-kappaB pathway in determining immunologic
      aberration.

PMID- 21905004
TI  - Proinflammatory Th17 cells are expanded and induced by dendritic cells in
      spondylarthritis-prone HLA-B27-transgenic rats.
AB  - OBJECTIVE: HLA-B27/human beta2-microglobulin-transgenic (B27-transgenic) rats, a
      model of spondylarthritis (SpA), develop spontaneous colitis and arthritis under
      conventional conditions. CD4+ T cells are pivotal in the development of
      inflammation in B27-transgenic rats. This study was undertaken to characterize
      the phenotype of CD4+ T cells in this model and to determine whether dendritic
      cells (DCs) induce proinflammatory T cells. METHODS: The phenotype of CD4+ T
      cells from rat lymph nodes (LNs) draining the sites of inflammation was analyzed
      by flow cytometry. Immunostaining was used to detect interleukin-17 (IL-17)
      producing cells in the rat joints. DCs from B27-transgenic or control rats
      (transgenic for HLA-B7 or nontransgenic) were cocultured with control CD4+ T
      cells and stimulated with anti-T cell receptor alpha/beta. RESULTS: IL-17A- and
      tumor necrosis factor alpha (TNFalpha)-producing CD4+ T cells were expanded in
      mesenteric and popliteal LNs from B27-transgenic rats. The accumulation of Th17
      cells correlated with disease development, in contrast to Th1 or Treg cells. IL
      17-positive mononuclear cells were detected in the arthritic joints of B27
      transgenic rats but not in the joints of control rats. Finally, in vitro
      cocultures demonstrated that Th17 cells were preferentially induced and expanded
      by DCs from B27-transgenic rats, by a process that may involve defective
      engagement of costimulatory molecules. CONCLUSION: Our findings indicate that
      expanded CD4+ T cells in B27-transgenic rats exhibit a proinflammatory Th17
      phenotype characterized by IL-17A and TNFalpha production. Furthermore, this
      population is preferentially induced by DCs from B27-transgenic rats. These data
      point toward an induction of Th17 cells as a possible pathogenic mechanism in
      this model of SpA. However, their pathogenic role still needs to be shown.

PMID- 21905005
TI  - Noncardiac vascular disease in rheumatoid arthritis: increase in venous
      thromboembolic events?
AB  - OBJECTIVE: To investigate the incidence of noncardiac vascular disease in a
      community-based incidence cohort of patients with rheumatoid arthritis (RA) and
      compare it to that in the general population and to investigate trends in the
      incidence of noncardiac vascular disease in patients with RA. METHODS: A
      population-based inception cohort of patients with incident RA between January 1,
      1980 and December 31, 2007 in Olmsted County, Minnesota and a cohort of non-RA
      subjects from the same population base was assembled and followed up until
      December 31, 2008. Venous thromboembolic, cerebrovascular, and peripheral
      arterial events were ascertained by medical record review. RESULTS: The study
      population included 813 patients with RA with a mean+/-SD age of 55.9+/-15.7
      years (68% women) and an average length of followup of 9.6+/-6.9 years. Compared
      to non-RA subjects of similar age and sex, patients diagnosed as having RA
      between 1995 and 2007 had a higher incidence (%) of venous thromboembolism
      (cumulative incidence+/-SE 6.7+/-1.7 versus 2.8+/-1.1, respectively; P=0.005) but
      similar rates of cerebrovascular and peripheral arterial events. Among patients
      with RA, the incidence of venous thromboembolic, cerebrovascular, and peripheral
      arterial events was similar in the 1995-2007 time period compared to the 1980
      1994 time period. CONCLUSION: Our findings indicate that the incidence of venous
      thromboembolism is increased in patients with RA compared to non-RA subjects. The
      incidence of cerebrovascular events and peripheral vascular disease events is
      similar in patients with RA compared to non-RA subjects. Among patients with RA,
      the incidence of noncardiac vascular disease has remained stable in recent
      decades.

PMID- 21905006
TI  - Protease-activated receptor 2, rather than protease-activated receptor 1,
      contributes to the aggressive properties of synovial fibroblasts in rheumatoid
      arthritis.
AB  - OBJECTIVE: To investigate whether protease-activated receptor 1 (PAR-1) and/or
      PAR-2 promotes the invasiveness/proliferation of synovial fibroblasts (SFs) and
      to determine the signaling mechanisms of these pathways. METHODS: SFs were
      isolated from the synovial tissue of patients with rheumatoid arthritis (RA),
      patients with osteoarthritis (OA), and PAR-1- or PAR-2-knockout (KO) mice.
      Expression of PAR-1 and PAR-2 was detected by immunofluorescence and Western
      blotting. The invasion and proliferation of SFs were measured by invasion assay
      and MTT assay, respectively. Matrix metalloproteinase 2 (MMP-2) and MMP-9 were
      detected by zymography, and cytokines were measured by enzyme-linked
      immunosorbent assay. RESULTS: PAR-1 and PAR-2 were colocalized with SFs in RA and
      OA synovium and, to a considerably lesser extent, in normal synovium. Inhibition
      of PAR-2 by small interfering RNA (siRNA) inhibited RASF invasion and
      proliferation, whereas blocking of PAR-1 by siRNA had the reverse effects. SFs
      from PAR-2-KO mice exhibited slower rates of proliferation and invasion. SFs from
      PAR-1-KO mice produced less MMP-2 and, in response to tumor necrosis factor alpha
      (TNFalpha) stimulation, had increased MMP-9 secretion when compared to SFs from
      wild-type and PAR-2-KO mice. Inhibition of PAR-1, but not PAR-2, stimulated the
      secretion of interleukin-17 (IL-17) and TNFalpha by RASFs. Furthermore, PAR-1 and
      PAR-2 had opposing effects on the activation of ERK, p38, and NF-kappaB.
      CONCLUSION: Activation of PAR-1 stimulates MMP-2 secretion, inhibits RASF growth
      and invasion, and decreases production of IL-17 and TNFalpha by RASFs, whereas
      activation of PAR-2 stimulates RASF growth and invasion and increases production
      of TNFalpha. Thus, although PAR-1 and PAR-2 are coexpressed by RASFs, PAR-2 alone
      appears to be responsible for the aggressive properties of RASFs and is likely to
      contribute to the pathologic progression of RA.

PMID- 21905007
TI  - Lack of a chondroprotective effect of cyclooxygenase 2 inhibition in a surgically
      induced model of osteoarthritis in mice.
AB  - OBJECTIVE: To investigate the chondroprotective effect of cyclooxygenase 2 (COX
      2) inhibition in experimental osteoarthritis (OA). METHODS: The expression of
      prostaglandin E2 synthetic enzymes was examined by immunostaining of tibial
      cartilage from mice with surgically induced knee joint instability and from OA
      patients undergoing total knee arthroplasty. The effect of orally administered
      celecoxib (10 mg/kg/day and 30 mg/kg/day) or vehicle alone in mice was examined
      12 weeks after the induction of OA. To investigate the involvement of COX-1 and
      COX-2 in OA development, we also created the model in COX-1-homozygous-knockout
      (Ptgs1-/-) mice and COX-2-homozygous-knockout (Ptgs2-/-) mice. OA severity was
      assessed using a grading system developed by our group and by the Osteoarthritis
      Research Society International scoring system. RESULTS: In mouse and human OA
      cartilage, the expression of the inducible enzymes COX-2 and microsomal
      prostaglandin E synthase 1 (mPGES-1) was enhanced, while that of the constitutive
      enzymes COX-1, cytosolic PGES, and mPGES-2 was suppressed. Daily celecoxib
      treatment did not prevent cartilage degradation or osteophyte formation during OA
      development in the mouse model. Furthermore, neither Ptgs1-/- mice nor Ptgs2-/-
      mice exhibited any significant difference in OA development as compared to wild
      type littermates. CONCLUSION: The two COX enzymes differ in terms of regulation
      of their expression during OA development. Nevertheless, experiments using
      inhibitor and genetic deficiency demonstrated a lack of chondroprotective effect
      of COX-2 inhibition in the mouse surgical OA model.

PMID- 21905008
TI  - A rare polymorphism in the gene for Toll-like receptor 2 is associated with
      systemic sclerosis phenotype and increases the production of inflammatory
      mediators.
AB  - OBJECTIVE: To investigate whether polymorphisms in Toll-like receptor (TLR)
      genes, previously reported to be associated with immune-mediated diseases, are
      involved in systemic sclerosis (SSc). METHODS: We genotyped 14 polymorphisms in
      the genes for TLRs 2, 4, 7, 8, and 9 in a discovery cohort comprising 452 SSc
      patients and 537 controls and a replication cohort consisting of 1,170 SSc
      patients and 925 controls. In addition, we analyzed 15-year followup data on 964
      patients to assess the potential association of TLR variants with the development
      of disease complications. We analyzed the functional impact of the associated
      polymorphism on monocyte-derived dendritic cells. RESULTS: In the discovery
      cohort, we observed that a rare functional polymorphism in TLR2 (Pro631His) was
      associated with antitopoisomerase (antitopo) positivity (odds ratio 2.24 [95%
      confidence interval 1.24-4.04], P=0.003). This observation was validated in the
      replication cohort (odds ratio 2.73 [95% confidence interval 1.85-4.04],
      P=0.0001). In addition, in the replication cohort the TLR2 variant was associated
      with the diffuse subtype of the disease (P=0.02) and with the development of
      pulmonary arterial hypertension (PAH) (Cox proportional hazards ratio 5.61 [95%
      confidence interval 1.53-20.58], P=0.003 by log rank test). Functional analysis
      revealed that monocyte-derived dendritic cells carrying the Pro63His variant
      produced increased levels of inflammatory mediators (tumor necrosis factor alpha
      and interleukin-6) upon TLR-2-mediated stimulation (both P<0.0001). CONCLUSION:
      Among patients with SSc, the rare TLR2 Pro631His variant is robustly associated
      with antitopoisomerase positivity, the diffuse form of the disease, and the
      development of PAH. In addition, this variant influences TLR-2-mediated cell
      responses. Further research is needed to elucidate the precise role of TLR-2 in
      the pathogenesis of SSc.

PMID- 21905009
TI  - Structural changes of the brain in rheumatoid arthritis.
AB  - OBJECTIVE: To investigate whether structural changes are present in the cortical
      and subcortical gray matter of the brains of patients with rheumatoid arthritis
      (RA). METHODS: We used two surface-based style morphometry analysis programs and
      a voxel-based style analysis program to compare high-resolution structural
      magnetic resonance imaging data obtained for 31 RA patients and 25 age- and sex
      matched healthy control subjects. RESULTS: We observed an increase in gray matter
      content in the basal ganglia of RA patients, mainly in the nucleus accumbens and
      caudate nucleus. There were no differences in the cortical gray matter. Moreover,
      patients had a smaller intracranial volume. CONCLUSION: Our results suggest that
      RA is associated with changes in the subcortical gray matter rather than with
      cortical gray matter atrophy. Since the basal ganglia play an important role in
      motor control as well as in pain processing and in modulating behavior in
      response to aversive stimuli, we suggest that these changes may result from
      altered motor control or prolonged pain processing. The differences in brain
      volume may reflect either generalized atrophy or differences in brain
      development.

PMID- 21905010
TI  - Heterogeneous nuclear RNPs as targets of autoantibodies in systemic rheumatic
      diseases.
AB  - OBJECTIVE: To investigate the abundance of autoantibodies to heterogeneous
      nuclear RNPs (hnRNPs) in systemic rheumatic diseases. METHODS: Recombinant human
      hnRNPs A1, B1, C1, E1, F, Gi, H1, I, K, and P2 were prepared. Antibodies to these
      antigens were determined by Western blotting and by enzyme-linked immunosorbent
      assay (ELISA) (for hnRNPs B1, E1, F, and H1) in serum samples obtained from
      patients with chronic fatigue syndrome (control subjects) and from patients with
      various connective tissue diseases. RESULTS: Western blotting analysis in 106
      control subjects and 298 patients with a connective tissue disease revealed that
      antibodies to all tested hnRNP antigens, except hnRNP Gi, were significantly more
      prevalent in patients with Sjogren's syndrome (SS) than in control subjects. The
      highest reactivity was observed for hnRNPs B1, E1, F, and H1 (reactivity in >45%
      of patients with SS and in 2.8% of control subjects). Reactivity with hnRNPs B1,
      E1, F, and H1 was also evaluated by ELISA in 89 control subjects and 228 patients
      with a connective tissue disease. Reactivity with at least 2 of the 4 tested
      antigens was observed in 1.1% of control subjects, 16% of patients with systemic
      lupus erythematosus (SLE), and 18% of patients with SS. Reactivity with at least
      3 of the 4 antigens was observed in 0% of the control subjects, 3.2% of patients
      with SLE, and 15% of patients with SS. CONCLUSION: Several hnRNPs are target
      antigens in SS. The combined presence of antibodies to several hnRNPs was
      strongly associated with connective tissue disease in general and with SS in
      particular.

PMID- 21905011
TI  - Antroquinonol differentially modulates T cell activity and reduces interleukin-18
      production, but enhances Nrf2 activation, in murine accelerated severe lupus
      nephritis.
AB  - OBJECTIVE: Accelerated severe lupus nephritis (ASLN), with an acute onset of
      severe clinical manifestations and histopathologic renal lesions, may represent
      transformation of mild LN to a severe form of glomerulonephritis. Abnormal
      activation of T and B cells and/or oxidative stress may play a major role in the
      pathogenesis of ASLN. This study tested the hypothesis that antroquinonol, a
      purified compound and major effective component of Antrodia camphorata with
      antiinflammatory and antioxidant activities, might prevent the transformation of
      mild LN into higher-grade (severe) nephritis in a murine lupus model. METHODS:
      Experimental ASLN was induced in (NZB*NZW)F1 mice by twice weekly intraperitoneal
      injections of Salmonella-type lipopolysaccharide (LPS). Starting 2 days after the
      first dose of LPS, mice were treated daily with antroquinonol, administered by
      gavage, for different durations up to 5 weeks. RESULTS: Antroquinonol
      administration significantly ameliorated the proteinuria, hematuria, impairment
      of renal function, and development of severe renal lesions, especially cellular
      crescent formation, neutrophil infiltration, fibrinoid necrosis, and T cell
      proliferation in the glomerulus, as well as periglomerular interstitial
      inflammation. Mechanistic analyses revealed that antroquinonol 1) inhibited T
      cell activation/proliferation, but enhanced Treg cell suppression and reduced
      renal production of interleukin-18 (IL-18); 2) inhibited production of reactive
      oxygen species and nitric oxide, but increased activation of Nrf2 in the kidney;
      and 3) suppressed renal inflammation via blocking of NF-kappaB activation.
      CONCLUSION: Antroquinonol may have therapeutic potential for the early treatment
      of ASLN via its differential regulation of T cell function and lowering of IL-18
      production, but also via the promotion of Nrf2 activation.

PMID- 21905013
TI  - Changing the outcome of osteoarthritis: still a challenge for cyclooxygenase 2
      inhibitors.

PMID- 21905012
TI  - Mechanisms involved in enhancement of the expression and function of aggrecanases
      by hyaluronan oligosaccharides.
AB  - OBJECTIVE: Small hyaluronan (HA) oligosaccharides serve as competitive receptor
      antagonists to displace HA from the cell surface and induce cell signaling
      events. In articular chondrocytes, this cell signaling is mediated by the HA
      receptor CD44 and induces stimulation of genes involved in matrix degradation,
      such as matrix metalloproteinases (MMPs) as well as matrix repair genes including
      type II collagen, aggrecan, and HA synthase 2. The objective of this study was to
      determine changes in the expression and function of aggrecanases after disruption
      of chondrocyte CD44-HA interactions. METHODS: Bovine articular chondrocytes or
      bovine cartilage tissue was pretreated with a variety of inhibitors of major
      signaling pathways prior to the addition of HA oligosaccharides. Changes in
      aggrecanase were monitored by real-time reverse transcription-polymerase chain
      reaction and Western blot analyses of ADAMTS-4, ADAMTS-5, and aggrecan
      proteolytic fragments. To test the interactions between ADAMTS-4 and membrane
      type 4 MMP (MT4-MMP), protein lysates purified from stimulated chondrocytes were
      subjected to coimmunoprecipitation. RESULTS: Disruption of chondrocyte CD44-HA
      interactions with HA oligosaccharides induced the transcription of ADAMTS-4 and
      ADAMTS-5 in a time- and dose-dependent manner. The association of glycosyl
      phosphatidylinositol-anchored MT4-MMP with ADAMTS-4 was also induced in articular
      chondrocytes by HA oligosaccharides. Inhibition of the NF-kappaB pathway blocked
      HA oligosaccharide-mediated stimulation of aggrecanases. CONCLUSION: Disruptive
      changes in chondrocyte-matrix interactions by HA oligosaccharides induce matrix
      degradation and elevate aggrecanases via the activation of the NF-kappaB
      signaling pathway.

PMID- 21905014
TI  - Interferon-gamma-independent suppression of Th17 cell differentiation by T-bet
      expression in mice with autoimmune arthritis.

PMID- 21905016
TI  - Defective DNA double-strand break repair in pediatric systemic lupus
      erythematosus.
AB  - OBJECTIVE: Previous reports of cells from patients with systemic lupus
      erythematosus (SLE) note that repair of single-strand breaks is delayed, and
      these lesions may be converted to double-strand breaks (DSBs) at DNA replication
      forks. We undertook this study to assess the integrity of DSB recognition,
      signaling, and repair mechanisms in B lymphoblastoid cell lines derived from
      patients with pediatric SLE. METHODS: Nine assays were used to interrogate DSB
      repair and recognition in lymphoblastoid cell lines from patients with pediatric
      SLE, including the neutral comet assay (NCA), colony survival assay (CSA),
      irradiation-induced foci formation for gamma-H2AX and 53BP1 proteins, kinetics of
      phosphorylation of structural maintenance of chromosomes protein 1 (SMC1),
      postirradiation bromodeoxyuridine incorporation to evaluate S phase checkpoint
      integrity, monoubiquitination of Fanconi protein D2, ATM protein expression, and
      non-homologous DNA end joining protein expression and function. RESULTS: Three of
      the 9 assays revealed abnormal patterns of response to irradiation-induced DNA
      damage. The NCA and CSA yielded aberrant results in the majority of SLE
      lymphoblastoid cell lines. Abnormal prolongation of SMC1 phosphorylation was also
      noted in 2 of 16 SLE lymphoblastoid cell lines. CONCLUSION: Our data suggest that
      DSB repair is defective in some lymphoblastoid cell lines from pediatric patients
      with SLE, especially when assessed by both NCA and CSA. Since these studies are
      nonspecific, further studies of DNA repair and kinetics are indicated to further
      delineate the underlying pathogenesis of SLE and possibly identify therapeutic
      targets.

PMID- 21905015
TI  - Beneficial effect of novel proteasome inhibitors in murine lupus via dual
      inhibition of type I interferon and autoantibody-secreting cells.
AB  - OBJECTIVE: To investigate the hypothesis that proteasome inhibition may have
      potential in the treatment of SLE, by targeting plasmacytoid dendritic cells
      (PDCs) and plasma cells, both of which are critical in disease pathogenesis.
      METHODS: Lupus-prone mice were treated with the nonselective proteasome
      inhibitors carfilzomib and bortezomib, the immunoproteasome inhibitor ONX 0914,
      or vehicle control. Tissue was harvested and analyzed by flow cytometry using
      standard markers. Nephritis was monitored by evaluation for proteinuria and by
      histologic analysis of kidneys. Serum anti-double-stranded DNA (anti-dsDNA)
      levels were measured by enzyme-linked immunosorbent assay (ELISA), and total IgG
      and dsDNA antibody-secreting cells (ASCs) by enzyme-linked immunospot assay.
      Human peripheral blood mononuclear cells or mouse bone marrow cells were
      incubated with Toll-like receptor (TLR) agonists and proteasome inhibitors, and
      interferon-alpha (IFNalpha) levels were measured by ELISA and flow cytometry.
      RESULTS: Early treatment of lupus-prone mice with the dual-targeting proteasome
      inhibitors carfilzomib or bortezomib or the immunoproteasome-specific inhibitor
      ONX 0914 prevented disease progression, and treatment of mice with established
      disease dramatically abrogated nephritis. Treatment had profound effects on
      plasma cells, with greater reductions in autoreactive than in total IgG ASCs, an
      effect that became more pronounced with prolonged treatment and was reflected in
      decreasing serum autoantibody levels. Notably, proteasome inhibition efficiently
      suppressed production of IFNalpha by TLR-activated PDCs in vitro and in vivo, an
      effect mediated by inhibition of both PDC survival and PDC function. CONCLUSION:
      Inhibition of the immunoproteasome is equally efficacious as dual targeting
      agents in preventing lupus disease progression by targeting 2 critical pathways
      in disease pathogenesis, type I IFN activation and autoantibody production by
      plasma cells.

PMID- 21905017
TI  - Overexpression of T-bet gene regulates murine autoimmune arthritis.
AB  - OBJECTIVE: To clarify the role of T-bet in the pathogenesis of collagen-induced
      arthritis (CIA). METHODS: T-bet-transgenic (Tg) mice under the control of the CD2
      promoter were generated. CIA was induced in T-bet-Tg mice and wild-type C57BL/6
      (B6) mice. Levels of type II collagen (CII)-reactive T-bet and retinoic acid
      receptor-related orphan nuclear receptor gammat (RORgammat) messenger RNA
      expression were analyzed by real-time polymerase chain reaction. Criss-cross
      experiments using CD4+ T cells from B6 and T-bet-Tg mice, as well as CD11c+
      splenic dendritic cells (DCs) from B6 and T-bet-Tg mice with CII were performed,
      and interleukin-17 (IL-17) and interferon-gamma (IFNgamma) in the supernatants
      were measured by enzyme-linked immunosorbent assay. CD4+ T cells from B6, T-bet
      Tg, or T-bet-Tg/IFNgamma-/- mice were cultured for Th17 cell differentiation,
      then the proportions of cells producing IFNgamma and IL-17 were analyzed by
      fluorescence-activated cell sorting. RESULTS: Unlike the B6 mice, the T-bet-Tg
      mice did not develop CIA. T-bet-Tg mice showed overexpression of Tbx21 and down
      regulation of Rorc in CII-reactive T cells. Criss-cross experiments with CD4+ T
      cells and splenic DCs showed a significant reduction in IL-17 production by CII
      reactive CD4+ T cells in T-bet-Tg mice, even upon coculture with DCs from B6
      mice, indicating dysfunction of IL-17-producing CD4+ T cells. Inhibition of Th17
      cell differentiation under an in vitro condition favoring Th17 cell
      differentiation was observed in both T-bet-Tg mice and T-bet-Tg/IFNgamma-/- mice.
      CONCLUSION: Overexpression of T-bet in T cells suppressed the development of
      autoimmune arthritis. The regulatory mechanism of arthritis might involve
      dysfunction of CII-reactive Th17 cell differentiation by overexpression of T-bet
      via IFNgamma-independent pathways.

PMID- 21905018
TI  - Soluble VE-cadherin in rheumatoid arthritis patients correlates with disease
      activity: evidence for tumor necrosis factor alpha-induced VE-cadherin cleavage.
AB  - OBJECTIVE: Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder
      that principally attacks synovial joints. However, accelerated atherosclerosis
      and increased cardiovascular morbidity and mortality are major clinical
      consequences of endothelial dysfunction in RA patients. Tumor necrosis factor
      alpha (TNFalpha) is the major mediator of inflammation in RA, related to vascular
      injury by targeting VE-cadherin, an endothelium-specific adhesion molecule of
      vital importance for endothelium integrity and angiogenesis. We undertook this
      study to examine the mechanisms regulating VE-cadherin processing by TNFalpha and
      their occurrence in RA. METHODS: Human umbilical vein endothelial cells were used
      in primary culture and treated with recombinant TNFalpha to study VE-cadherin
      cleavage. Cell lysates and conditioned media were analyzed by Western blotting
      for VE-cadherin cytoplasmic domain and extracellular domain (VE-90) generation,
      respectively. VE-90 was analyzed at baseline and at the 1-year followup in sera
      from 63 RA patients (from the Very Early Rheumatoid Arthritis cohort) with
      disease duration of <6 months. RESULTS: TNFalpha induced a time-dependent
      shedding of VE-90 in cell media. This effect was prevented by tyrosine kinase
      inhibitors (genistein and PP2) or by knocking down Src kinase. In contrast,
      tyrosine phosphatase blockade enhanced VE-cadherin cleavage, confirming the
      requirement of tyrosine phosphorylation processes. In addition, using the matrix
      metalloproteinase (MMP) activator APMA and the MMP inhibitor GM6001, we
      demonstrated that MMPs are involved in TNFalpha-induced VE-cadherin cleavage. Of
      major importance, VE-90 was detected in sera from the 63 RA patients and was
      positively correlated with the Disease Activity Score at baseline and after 1
      year followup. CONCLUSION: These findings provide the first evidence of VE
      cadherin proteolysis upon TNFalpha stimulation and suggest potential clinical
      relevance of soluble VE-cadherin in management of RA.

PMID- 21905019
TI  - Large candidate gene association study reveals genetic risk factors and
      therapeutic targets for fibromyalgia.
AB  - OBJECTIVE: Fibromyalgia (FM) represents a complex disorder that is characterized
      by widespread pain and tenderness and is frequently accompanied by additional
      somatic and cognitive/affective symptoms. Genetic risk factors are known to
      contribute to the etiology of the syndrome. The aim of this study was to examine
      >350 genes for association with FM, using a large-scale candidate gene approach.
      METHODS: The study group comprised 496 patients with FM (cases) and 348
      individuals with no chronic pain (controls). Genotyping was performed using a
      dedicated gene array chip, the Pain Research Panel, which assays variants
      characterizing >350 genes known to be involved in the biologic pathways relevant
      to nociception, inflammation, and mood. Association testing was performed using
      logistic regression. RESULTS: Significant differences in allele frequencies
      between cases and controls were observed for 3 genes: GABRB3 (rs4906902; P = 3.65
      * 10(-6)), TAAR1 (rs8192619; P = 1.11 * 10(-5)), and GBP1 (rs7911; P = 1.06 * 10(
      4)). These 3 genes and 7 other genes with suggestive evidence for association
      were examined in a second, independent cohort of patients with FM and control
      subjects who were genotyped using the Perlegen 600K platform. Evidence of
      association in the replication cohort was observed for TAAR1, RGS4, CNR1, and
      GRIA4. CONCLUSION: Variation in these 4 replicated genes may serve as a basis for
      development of new diagnostic approaches, and the products of these genes may
      contribute to the pathophysiology of FM and represent potential targets for
      therapeutic action.

PMID- 21905020
TI  - Cyclic loading increases friction and changes cartilage surface integrity in
      lubricin-mutant mouse knees.
AB  - OBJECTIVE: To investigate the effects of lubricin gene dosage and cyclic loading
      on whole joint coefficient of friction and articular cartilage surface integrity
      in mouse knee joints. METHODS: Joints from mice with 2 (Prg4(+/+)), 1 (Prg4(+/
      )), or no (Prg4(-/-)) functioning lubricin alleles were subjected to 26 hours of
      cyclic loading using a custom-built pendulum. Coefficient of friction values were
      measured at multiple time points. Contralateral control joints were left
      unloaded. Following testing, joints were examined for histologic evidence of
      damage and cell viability. RESULTS: At baseline, the coefficient of friction
      values in Prg4(-/-) mice were significantly higher than those in Prg4(+/+) and
      Prg4(+/-) mice (P < 0.001). Cyclic loading continuously increased the coefficient
      of friction in Prg4(-/-) mouse joints. In contrast, Prg4(+/-) and Prg4(+/+) mouse
      joints had no coefficient of friction increases during the first 4 hours of
      loading. After 26 hours of loading, joints from all genotypes had increased
      coefficient of friction values compared to baseline and unloaded controls.
      Significantly greater increases occurred in Prg4(-/-) and Prg4(+/-) mouse joints
      compared to Prg4(+/+) mouse joints. The coefficient of friction values were not
      significantly associated with histologic evidence of damage or loss of cell
      viability. CONCLUSION: Our findings indicate that mice lacking lubricin have
      increased baseline coefficient of friction values and are not protected against
      further increases caused by loading. Prg4(+/-) mice are indistinguishable from
      Prg4(+/+) mice at baseline, but have significantly greater coefficient of
      friction values following 26 hours of loading. Lubricin dosage affects joint
      properties during loading, and may have clinical implications in patients for
      whom injury or illness alters lubricin abundance.

PMID- 21905022
TI  - CD4+ Foxp3+ regulatory T cells mediate Toxoplasma gondii-induced T-cell
      suppression through an IL-2-related mechanism but independently of IL-10.
AB  - Acute Toxoplasma gondii infection comprises an immunosuppression stage,
      characterized by a reduction in T-cell proliferation in vitro. Treg cells
      maintain the homeostasis of the immune system, but their role in T. gondii
      induced suppression has not been addressed. We show herein that
      immunosuppression, affecting both CD4(+)  and CD8(+)  T-cell proliferation,
      concurs with a reduction in Treg-cell number. The residual Treg cells, however,
      are activated and display an increased suppressive capacity. We show that
      selective elimination of Treg cells using Foxp3(EGFP)  mice leads to a full
      recovery of CD4(+)  and CD8(+)  T-cell proliferation. After Treg-cell removal, a
      reduced production of IL-10 was observed, but IL-2 levels were unchanged. The
      numbers of IL-10-producing Treg cells also increased during infection, although
      the in vitro neutralization of this cytokine did not modify T-cell proliferation,
      suggesting that IL-10 does not mediate the Treg-mediated suppression. However,
      addition of rIL-2 in vitro fully restored T-cell proliferation from infected
      animals. Thus, we show that Treg cells mediate the T-cell suppression observed
      during acute T. gondii infection through an IL-2-dependent mechanism. Our results
      provide novel insights into the regulation of the immune response against T.
      gondii.

PMID- 21905023
TI  - Human tumor-induced and naturally occurring Treg cells differentially affect NK
      cells activated by either IL-2 or target cells.
AB  - NK cells play a crucial role in the eradication of tumor cells. Naturally
      occurring (n) Treg cells and induced (i) Treg cells are two distinct Treg
      subsets. While the interaction of nTreg cells with NK cells has been investigated
      in the past, the role of tumor iTreg cells in the modulation of NK-cell function
      remains unclear. Tumor iTreg cells were generated from CD4(+) CD25(-)  T cells in
      the presence of autologous immature DCs, head and neck cancer cells and IL-2, IL
      10, and IL-15. The effect of iTreg cells and nTreg cells on the expression of
      NKG2D, NKp44, CD107a, and IFN-gamma by NK cells, as well as NK tumor-cytolytic
      activity, were investigated. iTreg cells - similar to recombinant TGF-beta and
      nTreg cells - inhibited IL-2-induced activation of NK cells in the absence of
      target cell contact. Surprisingly, and in contrast to nTreg cells, iTreg cells
      enhanced NK-cell activity elicited by target cell contact. The cytolytic activity
      of NK cells activated by iTreg cells was mediated via perforin and FasL. We
      conclude that tumor iTreg cells inhibited IL-2-mediated NK-cell activity in the
      absence of target cells, whereas the tumoricidal activity of NK cells was
      enhanced by iTreg cells. Our data suggest a complex, previously not recognized,
      differential regulation of human NK activity by iTreg cells in the tumor
      microenvironment.

PMID- 21905024
TI  - Persistence of IL-2 expressing Th17 cells in healthy humans and experimental
      autoimmune uveitis.
AB  - Compared with other T-helper subsets, Th17 cell numbers are very low in human
      blood but become elevated in chronic inflammatory diseases. In this study, we
      investigated mechanisms that may explain the frequent involvement of Th17 cells
      in autoimmune diseases such as uveitis. We compared Th17 and Th1 subsets and
      found that Th17 cells expressed lower IL-2 levels during Ag-priming and this
      correlated with their decreased susceptibility to activation-induced cell death
      (AICD). However, complete depletion of IL-2 with IL-2 neutralizing antibodies
      rendered Th17 cells as susceptible to apoptosis as Th1 cells, suggesting that the
      low levels of IL-2 produced by Th17 cells conferred survival advantages to this
      subset. We describe here a Th17 subtype that constitutively produces very low
      levels of IL-2 (Th17-DP). The Th17-DP population increased dramatically in the
      blood and retina of mice during experimental autoimmune uveitis, indicating their
      potential involvement in the etiology of uveitis. We further show that the
      majority of the memory Th17 cells in human blood are Th17-DP and are targets of
      daclizumab, an IL-2R antibody used in treating recalcitrant uveitis. Thus, Th17
      cells may persist in tissues and contribute to chronic inflammation by limiting
      IL-2 production to levels that cannot provoke IL-2-induced AICD yet are
      sufficient to promote Th17 homeostatic expansion.

PMID- 21905025
TI  - The effects of different methods of emotional disclosure: differentiating post
      traumatic growth from stress symptoms.
AB  - Research on emotional disclosure should test the effects of different disclosure
      methods and whether symptoms are affected differently than post-traumatic growth.
      We randomized 214 participants with unresolved stressful experiences to four
      disclosure conditions (written, private spoken, talking to a passive listener,
      talking to an active facilitator) or two control conditions. All groups had one
      30-minute session. After 6 weeks, disclosure groups reported more post-traumatic
      growth than controls, and disclosure conditions were similar in this effect. All
      groups decreased in stress symptoms (intrusions, avoidance, psychological and
      physical symptoms), but disclosure did not differ from control. We conclude that
      30 minutes of disclosure leads to post-traumatic growth but not necessarily
      symptom reduction, and various disclosure methods have similar effects. Research
      on the effects of disclosure should focus on the benefits of growth as well as
      symptom reduction.

PMID- 21905026
TI  - Effects of stress, depression, and their interaction on heart rate, skin
      conductance, finger temperature, and respiratory rate: sympathetic
      parasympathetic hypothesis of stress and depression.
AB  - We examined effects of stress, depression, and their interaction on sympathetic
      parasympathetic responses, including percentage heart rate (PHR), percentage skin
      conductance (PSC), percentage finger temperature (PTEMP), and percentage
      respiratory rate (PRESPR). Participants were categorized into normal, low-risk,
      and high-risk depression groups under stress or no-stress by measuring
      psychophysiological responses. Stress increased PHR and PSC and decreased PTEMP.
      Depression negatively correlated with PHR and PTEMP. PSC and PTEMP were
      significantly dependent on and positively correlated with depression. PTEMP was
      significantly affected by the stress and depression interaction. Stress affects
      sympathetic, rather than parasympathetic, activity. Depression and the
      interaction between stress and depression initially associated with the
      sympathetic division and are then correlated with parasympathetic activity. A
      sympathetic-parasympathetic hypothesis and its clinical implications are
      discussed.

PMID- 21905027
TI  - Physicochemical stability of solid dispersions of enantiomeric or racemic
      ibuprofen in stearic acid.
AB  - The aim of this study was to investigate the solid dispersion phase behavior of s
      or rs-ibuprofen in stearic acid. By means of thermal analysis, we have
      demonstrated the total immiscibility, in solid state, of the corresponding binary
      mixtures. This indicates that no specific interactions exist between the chosen
      excipient and active pharmaceutical ingredient (API) that lead to eutectic
      systems. Furthermore, based on calorimetric and X-ray diffraction experiments, we
      have showed that upon cooling of the molten state, only stearic acid
      recrystallizes in the presence of s-ibuprofen, whereas a quaternary phase mixture
      is obtained for the racemic ibuprofen/stearic acid preparation. The solubility of
      stearic acid in s-ibuprofen liquid in all proportions was also determined.
      Overall, the results presented here offer an approach for the study of
      API/excipient interactions.

PMID- 21905028
TI  - Transport of the synthetic opioid peptide DADLE ([D-Ala2,D-Leu5]-enkephalin) in
      neuronal cells.
AB  - The sodium-coupled oligopeptide transporters 1 and 2 (SOPT1 and SOPT2) transport
      peptides consisting of at least five amino acids and show potential for the
      delivery of therapeutically relevant peptides/peptidomimetics. Here, we examined
      the expression of these two transporters in the retinal neuronal cell line RGC-5.
      These cells showed robust uptake activity for the synthetic pentapeptide DADLE
      ([D-Ala(2),D-Leu(5)]-Enkephalin). The uptake was Na(+) dependent and saturable
      (K(t), 6.2 +/- 0.6 MUM). A variety of oligopeptides inhibited DADLE uptake. The
      uptake of the competing oligopeptides was directly demonstrated with fluorescein
      isothiocyanate-labeled Tyr-Gly-Gly-Phe-Leu-Arg-Arg-Ile-Arg-Pro-Lys-Leu-Lys in RGC
      5 cells and primary mouse retinal ganglion cells. The characteristics of DADLE
      uptake matched those of SOPT2. We then examined the expression of SOPT1 in these
      cells with deltorphin II (Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH(2)) as the substrate
      and found that RGC-5 cells also expressed SOPT1. As it is already known that
      SOPT1 is expressed in the neuronal cell line SK-N-SH, we investigated SOPT2
      expression in these cells to determine whether the presence of both oligopeptide
      transporters is a common feature of neuronal cells. These studies showed that SK
      N-SH cells also expressed SOPT2. This constitutes the first report on the
      functional characterization of SOPT1 and SOPT2 in retinal neuronal cells and on
      the expression of SOPT2 in nonretinal neuronal cells.

PMID- 21905029
TI  - A survey of top 200 drugs--inconsistent practice of drug strength expression for
      drugs containing salt forms.
AB  - Many ionizable drugs are developed and marketed as salt forms. However, there are
      no clear US regulatory guidelines on drug strength labeling for salts. The
      strengths of some drugs are expressed as salts and some as free acids/bases. This
      study surveyed the top 200 US drugs to assess the common practice in industry.
      The top 200 drugs prescribed in the United States were included in this survey.
      The drugs containing active pharmaceutical ingredient (API) salts were selected
      for analysis. Generic or combination products with redundant API salts were
      excluded. The package insert of each selected drug was reviewed, and the
      information on drug strength expression was extracted and categorized. Out of the
      top 200 drugs, 59 unique API salts were identified. The drug strengths were
      expressed as salts for 32 drugs (54%) and as free acids/bases for 27 drugs (46%).
      The survey results revealed the inconsistent practice among the industries
      regarding the drug strength expression for salts. Non-harmonized labeling
      practice can lead to confusions, potential calculation/dosing errors, and
      complications in labeling new products. The authors recommend the US Food and
      Drug Administration to standardize the labeling format for salts and preferably
      express the drug strengths based on the free acid/base forms.

PMID- 21905030
TI  - An adsorption chromatography assay to probe bulk particle transport through
      hydrogels.
AB  - Biopolymer-based hydrogels such as mucus and the basal lamina play a key role in
      biology, where they control the exchange of material between different
      compartments. They also pose a barrier that needs to be overcome for successful
      drug delivery. Characterizing the permeability properties of such hydrogels is
      mandatory for the development of suitable drug delivery vectors and
      pharmaceutics. Here, we present an experimental method to measure bulk particle
      transport through hydrogels. We validate our assay by applying it to mucin
      hydrogels and show that the permeability properties of these mucin hydrogels can
      be modulated by polymer density and pH, in agreement with previous results
      obtained from single particle tracking. The method we present here is easy to
      handle, inexpensive, and high-throughput compatible. It is also a suitable
      platform for the design and screening of drugs that aim at modifying the barrier
      properties of hydrogels. This system can also aid in the characterization and
      development of synthetic gels for a range of biomedical applications.

PMID- 21905031
TI  - Pharmacokinetic interplay of phase II metabolism and transport: a theoretical
      study.
AB  - Understanding of the interdependence of cytochrome P450 enzymes and P
      glycoprotein in disposition of drugs (also termed "transport-metabolism
      interplay") has been significantly advanced in recent years. However, whether
      such "interplay" exists between phase II metabolic enzymes and efflux
      transporters remains largely unknown. The objective of this article is to explore
      the role of efflux transporters (acting on the phase II metabolites) in
      disposition of the parent drug in Caco-2 cells, liver, and intestine via
      simulations utilizing a catenary model (for Caco-2 system) and physiologically
      based pharmacokinetic (PBPK) models (for the liver and intestine). In all three
      models, "transport-metabolism interplay" (i.e., inhibition of metabolite efflux
      decreases the metabolism) can be observed only when futile recycling (or
      deconjugation) occurred. Futile recycling appeared to bridge the two processes
      (i.e., metabolite formation and excretion) and enable the interplay thereof.
      Without futile recycling, metabolite formation was independent on its downstream
      process excretion, thus impact of metabolite excretion on its formation was
      impossible. Moreover, in liver PBPK model with futile recycling, impact of
      biliary metabolite excretion on the exposure of parent drug [(systemic
      (reservoir) area under the concentration-time curve (AUC(R1))] was limited; a
      complete inhibition of efflux resulted in AUC(R1) increases of less than 1-fold
      only. In intestine PBPK model with futile recycling, even though a complete
      inhibition of efflux could result in large elevations (e.g., 3.5-6.0-fold) in
      AUC(R1), an incomplete inhibition of efflux (e.g., with a residual activity of >=
      20% metabolic clearance) saw negligible increases (<0.9-fold) in AUC(R1). In
      conclusion, this study presented mechanistic observations of pharmacokinetic
      interplay between phase II enzymes and efflux transporters. Those studying such
      "interplay" are encouraged to adequately consider potential consequences of
      inhibition of efflux transporters in humans.

PMID- 21905032
TI  - Stability of IgG1 monoclonal antibodies in intravenous infusion bags under
      clinical in-use conditions.
AB  - Compounding pharmacists are expected to prepare safe and efficacious doses of
      medication under time and economical constraints while protecting pharmacy staff
      and caregivers from inadvertent exposure to the drug. The pharmacist has the
      additional responsibility to ensure that the product is stable in the final
      administrated form as the time between drug preparation and administration is
      considerable. Pharmacists are responsible for setting a "beyond-use" date based
      on United States Pharmacopeia 797, wherein the beyond-use date for the compounded
      sterile preparation (CSP) is defined as the time by which the compounded
      preparation must be used to avoid risks for product degradation, contamination,
      and so on. Physical and chemical stability of the CSP can be difficult to
      maintain over extended storage, especially since the formulation components are
      diluted within the intravenous (i.v.) bag contents. Recent published reports have
      suggested the use of extended time, beyond that recommended by the manufacturer,
      for the storage and administration of CSP. These recommendations were based on
      inadequate analytical testing of the CSP. Herein, we demonstrate that setting of
      the beyond-use date should be carefully assessed using the appropriate analytical
      methods and testing. Results from our studies clearly indicate that many of the
      tested IgG(1) monoclonal antibodies should not be diluted and stored in i.v. bags
      over extended period of time, and particularly should not be transported after
      dilution in the infusion bags without consulting the manufacturer. Results from
      this study also indicate that i.v. bag agitation studies should be performed
      during pharmaceutical development of protein therapeutics under clinical in-use
      conditions, especially when storage and transportation of i.v. bags are possible
      in global clinical trials and post-licensure usage.

PMID- 21905033
TI  - Lipid nanoparticles as carrier for octyl-methoxycinnamate: in vitro percutaneous
      absorption and photostability studies.
AB  - The aim of the present study was the evaluation of lipid nanoparticles (solid
      lipid nanoparticles, SLN, and nanostructured lipid carriers, NLC) as potential
      carriers for octyl-methoxycinnamate (OMC). The release pattern of OMC from SLN
      and NLC was evaluated in vitro, determining its percutaneous absorption through
      excised human skin. Additional in vitro studies were performed in order to
      evaluate, after UVA radiation treatment, the spectral stability of OMC-loaded
      lipid nanoparticles. From the obtained results, ultrasonication method yielded
      both SLN and NLC in the nanometer range with a high active loading and a particle
      shape close to spherical. Differential scanning calorimetry data pointed out the
      key role of the inner oil phase of NLC in stabilizing the particle architecture
      and in increasing the solubility of OMC as compared with SLN. In vitro results
      showed that OMC, when incorporated in viscosized NLC dispersions (OMC-NLC),
      exhibited a lower flux with respect to viscosized SLN dispersions (OMC-SLN) and
      two reference formulations: a microemulsion (OMC-ME) and a hydroalcoholic gel
      (OMC-GEL). Photostability studies revealed that viscosized NLC dispersions were
      the most efficient at preserving OMC from ultraviolet-mediated photodegradation.

PMID- 21905035
TI  - Freeze-drying of nanosuspensions, part 3: investigation of factors compromising
      storage stability of highly concentrated drug nanosuspensions.
AB  - On the basis of a previously developed formulation and process guideline for
      lyophilized, highly concentrated drug nanosuspensions for parenteral use, it was
      the purpose of this study to demonstrate that the original nanoparticle size
      distribution can be preserved over a minimum period of 3 months, even if
      aggressive primary drying conditions are used. Critical factors were evaluated
      that were originally believed to affect storage stability of freeze-dried drug
      nanoparticles. It was found that the nature and concentration of the steric
      stabilizer, such as Poloxamer 338 and Cremophor EL, are the most important
      factors for long-term stability of such formulations, independent of the used
      drug compound. The rational choice of an adequate steric stabilizer, namely
      Poloxamer 338, in combination with various lyoprotectants seems crucial to
      prevent physical instabilities of the lyophilized drug nanoparticles during short
      term stability experiments at ambient and accelerated conditions. A 200 mg/mL
      concentration of nanoparticles could successfully be stabilized over the
      investigated time interval. In the course of the present experiments,
      polyvinylpyrrolidone, type K15 was found superior to trehalose or sucrose in
      preserving the original particle size distribution, presumably based on its
      surface-active properties. Lastly, it was demonstrated that lower water contents
      are generally beneficial to stabilize such systems.

PMID- 21905036
TI  - Stability of human growth hormone in supercritical carbon dioxide.
AB  - The instability of human growth hormone (hGH) to temperature and interfaces makes
      its formulation into injectable, sustained-release drug delivery systems
      challenging. A novel method of encapsulating hGH in polymeric microparticles has
      been developed using supercritical CO(2) (scCO(2)) technology, but there is
      limited understanding of the stability of hGH within this system. The aim of this
      study was to evaluate the stability of hGH in scCO(2) processing. The integrity
      of the protein was assessed following exposure to scCO(2) using a range of
      different analytical techniques. Mass spectrometry showed that no peptide
      cleavage occurred as a result of processing or exposure to scCO(2). Size
      exclusion chromatography detected formation of aggregates at high temperatures,
      but not as a result of the encapsulation process. Reverse-phase chromatography
      demonstrated that the production of deamidation products occurred as a function
      of temperature, but only at temperatures higher than those used for the
      encapsulation process. Circular dichroism and infrared spectroscopy demonstrated
      that the use of scCO(2) was not detrimental to the secondary molecular structure
      of hGH. Together, these results show that the structural integrity of hGH is
      unaffected by scCO(2) processing and that hGH can be successfully encapsulated in
      polymer microparticles using this technique.

PMID- 21905034
TI  - Stable dry powder formulation for nasal delivery of anthrax vaccine.
AB  - There is a current biodefense interest in protection against anthrax. Here, we
      developed a new generation of stable and effective anthrax vaccine. We studied
      the immune response elicited by recombinant protective antigen (rPA) delivered
      intranasally with a novel mucosal adjuvant, a mast cell activator compound 48/80
      (C48/80). The vaccine formulation was prepared in a powder form by spray-freeze
      drying (SFD) under optimized conditions to produce particles with a target size
      of D(50) = 25 MUm, suitable for delivery to the rabbit nasal cavity.
      Physicochemical properties of the powder vaccines were characterized to assess
      their delivery and storage potential. Structural stability of rPA was confirmed
      by circular dichroism and attenuated total reflectance-Fourier transform infrared
      spectroscopy, whereas functional stability of rPA and C48/80 was monitored by
      cell-based assays. Animal study was performed using a unit-dose powder device for
      direct nasal application. Results showed that C48/80 provided effective mucosal
      adjuvant activity in rabbits. Freshly prepared SFD powder vaccine formulations or
      powders stored for over 2 years at room temperature elicited significantly
      elevated serum PA-specific and lethal toxin neutralization antibody titers that
      were comparable to that induced by intramuscular immunization with rPA. Nasal
      delivery of this vaccine formulation may be a viable alternative to the currently
      licensed vaccine or an attractive vaccine platform for other mucosally
      transmitted diseases.

PMID- 21905037
TI  - Understanding the performance of melt-extruded poly(ethylene oxide)-bicalutamide
      solid dispersions: characterisation of microstructural properties using thermal,
      spectroscopic and drug release methods.
AB  - In this article, we have prepared hot-melt-extruded solid dispersions of
      bicalutamide (BL) using poly(ethylene oxide) (PEO) as a matrix platform. Prior to
      preparation, miscibility of PEO and BL was assessed using differential scanning
      calorimetry (DSC). The onset of BL melting was significantly depressed in the
      presence of PEO, and using Flory-Huggins (FH) theory, we identified a negative
      value of -3.4, confirming miscibility. Additionally, using FH lattice theory, we
      estimated the Gibbs free energy of mixing which was shown to be negative, passing
      through a minimum at a polymer fraction of 0.55. Using these data, solid
      dispersions at drug-to-polymer ratios of 1:10, 2:10 and 3:10 were prepared via
      hot-melt extrusion. Using a combination of DSC, powder X-ray diffractometry and
      scanning electron microscopy, amorphous dispersions of BL were confirmed at the
      lower two drug loadings. At the 3:10 BL to PEO ratio, crystalline BL was
      detected. The percent crystallinity of PEO was reduced by approximately 10% in
      all formulations following extrusion. The increased amorphous content within PEO
      following extrusion accommodated amorphous BL at drug to polymer loadings up to
      2:10; however, the increased amorphous domains with PEO following extrusion were
      not sufficient to fully accommodate BL at drug-to-polymer ratios of 3:10.

PMID- 21905038
TI  - Contribution of organic cation transporter 3 to cisplatin cytotoxicity in human
      cervical cancer cells.
AB  - This study was conducted to investigate whether drug transporters play a role in
      determination of cisplatin resistance in cervical cancer cells. The transcript
      levels of the transporter genes previously associated with cisplatin transport
      and/or resistance were compared between the cisplatin-sensitive cervical
      adenocarcinoma KB-3-1 and its derivative cisplatin-resistant KB-CP20 cells. The
      expression of the efflux transporter gene multidrug resistance-associated protein
      2 (MRP2) was significantly reduced in KB-CP20 cells, in support of previous
      studies indicating that MRP2 is unlikely responsible for cisplatin resistance in
      these cells. We observed that the expression of the uptake transporter organic
      cation transporter 3 (OCT3) was extremely downregulated in KB-CP20 compared with
      KB-3-1 cells. Consistently, the transport function for organic cations in the
      former was considerably low. OCT3 overexpression significantly increased
      cisplatin cellular accumulation and cytotoxicity in KB-3-1 cells, while its
      downregulation by short hairpin RNA or chemical inhibition increased the
      resistance. Interestingly, there was no effect of OCT3 overexpression on
      cisplatin accumulation and cytotoxicity in human embryonic kidney 293 cells. The
      present study indicates that OCT3 partially contributes to the sensitivity of
      cervical adenocarcinoma cells to cisplatin cytotoxicity. Further studies are
      required to determine OCT3 activity in cervical cancer tissues of different
      cisplatin chemoresponses and to elucidate the underlying mechanisms of different
      OCT3 function in different cell types.

PMID- 21905039
TI  - Violent and nonviolent video games differentially affect physical aggression for
      individuals high vs. low in dispositional anger.
AB  - Although numerous experiments have shown that exposure to violent video games
      (VVG) causes increases in aggression, relatively few studies have investigated
      the extent to which this effect differs as a function of theoretically relevant
      individual difference factors. This study investigated whether video game content
      differentially influences aggression as a function of individual differences in
      trait anger. Participants were randomly assigned to play a violent or nonviolent
      video game before completing a task in which they could behave aggressively.
      Results showed that participants high in trait anger were the most aggressive,
      but only if they first played a VVG. This relationship held while statistically
      controlling for dimensions other than violent content on which game conditions
      differed (e.g. frustration, arousal). Implications of these findings for models
      explaining the effects of video games on behavior are discussed.

PMID- 21905040
TI  - What do the 2011 American Heart Association guidelines tell us about prevention
      of cardiovascular disease in women?
AB  - The 2011 Update of the American Heart Association's Cardiovascular Disease
      Prevention Guideline for Women is designed to help women and their physicians
      understand cardiovascular Disease (CVD) risks and undertake practical steps that
      are most effective in preventing heart disease and stroke. Defining a woman's
      risk status and improving her adherence to preventive lifestyle behaviors and
      medications is the best strategy to lower the burden of CVD in women.

PMID- 21905041
TI  - Correlation between heart rate control during exercise and exercise capacity in
      patients with chronic atrial fibrillation.
AB  - BACKGROUND: Rate control is an acceptable alternative to rhythm control in
      patients with chronic atrial fibrillation (AF). HYPOTHESIS: The aim of this study
      of AF patients was to understand the correlation between their exercise capacity
      and both heart rate (HR) and HR variation index during exercise. METHODS: The
      exercise capacity of 85 male patients with chronic AF was measured using a
      cardiopulmonary exercise test (CPX). Within this population, we compared the
      exercise tolerance of patients with a normal chronotropic response (maximal HR
      85%-115% that of the maximal age-predicted HR during CPX) to those whose HR
      response exceeded this range. Two similar comparisons were made by dividing the
      subject population according to (1) whether or not their HR variation index
      (HRVI) during CPX exceeded 10 bpm/min, and (2) whether their HR during the 6
      minute walk test exceeded 110 bpm. RESULTS: Patients with an HRVI not over 10
      bpm/min showed higher maximal oxygen uptake compared to patients with a higher
      HRVI (26.7 +/- 6.1 vs 22.8 +/- 4.8 mL O(2) /kg/min, P = 0.002) and a longer
      distance walked during CPX (705.6 +/- 200.3 vs 520.9 +/- 155.5 m, P<0.001). No
      other significant influence on exercise capacity was seen. Multivariate
      regression analysis revealed that both the body mass index and the HRVI during
      CPX were independent predictors of the maximal oxygen uptake. CONCLUSIONS: Better
      HRVI control on CPX was correlated with better exercise capacity in patients with
      chronic AF.

PMID- 21905042
TI  - Comparison of electrocardiographic findings between the midventricular ballooning
      form and apical ballooning form of takotsubo cardiomyopathy.
AB  - BACKGROUND: Several reports have recently described the variant form of takotsubo
      cardiomyopathy exhibiting midventricular ballooning. The purpose of this study
      was to assess electrocardiographic (ECG) findings on admission in patients with
      midventricular ballooning. HYPOTHESIS: ECG findings are different between the
      midventricular ballooning form and apical ballooning form of takotsubo
      cardiomyopathy. METHODS: We reviewed ECGs on admission in 6 patients with
      midventricular ballooning and 20 patients with apical ballooning. The sum of ST
      segment elevation in leads V1 to V3 or in leads V4 to V6 was obtained. The number
      of leads showing ST segment elevation and/or T wave inversion was also obtained.
      These ECG findings were compared between the 2 groups. RESULTS: In midventricular
      ballooning, ECG changes including ST segment elevation and/or T wave inversion
      were observed frequently in leads V2 and V3, and were not observed in leads II,
      III, -aVR, aVF, V5, and V6. On the other hand, in apical ballooning, they were
      found in all leads. They were most common in leads V4 and V5. The sum of ST
      segment elevation in leads V1 to V3 was similar (2.6 +/- 2.0 mm vs 2.7 +/- 2.0
      mm, P = not significant), and the sum of ST segment elevation in leads V4 to V6
      was significantly lower in midventricular ballooning than apical ballooning (0.4
      +/- 0.8 mm vs 3.5 +/- 3.0 mm, P<0.05). The number of leads showing ST segment
      elevation and/or T wave inversion was significantly lower in midventricular
      ballooning than apical ballooning (3.2 +/- 1.0 leads vs 6.3 +/- 2.2 leads,
      P<0.01). CONCLUSIONS: Our data suggested that midventricular ballooning may show
      limited ECG changes despite broad wall motion abnormality.

PMID- 21905044
TI  - Development and validation of a capillary electrophoresis assay for the
      determination of the stereoisomeric purity of chloroquine enantiomers.
AB  - A stereoselective CE assay for the determination of the enantiomeric purity of
      (R)-(-)-chloroquine and (S)-(+)-chloroquine was developed and validated. The
      separations were performed in a 50.2/40 cm uncoated fused silica capillary at 20
      degrees C using a 100 mM sodium phosphate buffer, pH 2.5, containing 30 mg/mL
      sulfobutylether(VII)-beta-cyclodextrin as background electrolyte operated at an
      applied voltage of -25 kV and 20 degrees C. The detection wavelength was 225 nm.
      Carbamazepine was used as internal standard. The assay was validated in the range
      of 0.05-1.0% for the respective minor chloroquine enantiomer based on a
      concentration of 3 mg/mL of the major enantiomer, either (R)-(-)-chloroquine or
      (S)-(+)-chloroquine. The method was applied to analyze the stereoisomeric purity
      of synthetic samples of the chloroquine enantiomers.

PMID- 21905043
TI  - Impact of diabetes mellitus on the clinical management of global cardiovascular
      risk: analysis of the results of the Evaluation of Final Feasible Effect of
      Control Training and Ultra Sensitization (EFFECTUS) educational program.
AB  - BACKGROUND: The Evaluation of Final Feasible Effect of Ultra Control Training and
      Sensitization (EFFECTUS) study is aimed at implementing global cardiovascular
      (CV) risk management in Italy. HYPOTHESIS: To evaluate the impact of diabetes
      mellitus (DM) on attitudes and preferences for clinical management of global CV
      risk among physicians treating diabetic or nondiabetic patients. METHODS:
      Involved physicians were asked to submit data into a study-designed case-report
      form, covering the first 10 adult outpatients consecutively seen in May 2006. All
      available clinical data were centrally analyzed for global CV risk assessment and
      CV risk profile characterization. Patients were stratified according to the
      presence or absence of DM. RESULTS: Overall, 1078 physicians (27% female, ages 50
      +/- 7 y) collected data of 9904 outpatients (46.5% female, ages 67 +/- 9 y),
      among whom 3681 (37%) had a diagnosis of DM at baseline. Diabetic patients were
      older and had higher prevalence of obesity, hypertension, dyslipidemia, and
      associated CV diseases than nondiabetic individuals (P<0.001). They had higher
      systolic blood pressure, total cholesterol, triglycerides, and creatinine levels,
      but lower high-density lipoprotein cholesterol levels than nondiabetic patients
      (P<0.001). Higher numbers of blood pressure and lipid-lowering drugs and
      antiplatelet agents were used in diabetic than in nondiabetic patients (P<0.001).
      CONCLUSIONS: The EFFECTUS study confirmed higher CV risk and more CV drug
      prescriptions in diabetic than in nondiabetic patients. Presence of DM at
      baseline significantly improved clinical data collection. Such an approach,
      however, was not paralleled by a better control of global CV risk profile, which
      was significantly worse in the former than in the latter group.

PMID- 21905045
TI  - Enantioseparation of organic acids of pharmaceutical interest using eremomycin as
      a chiral selector.
AB  - Strong adsorption of eremomycin on the fused-silica capillary wall was used for
      separation of enantiomers by CE. The capillary with adsorbed chiral selector was
      shown to be easily prepared and has reproducible properties. The effect of the
      chiral selector concentration, pH and composition of the BGE, and applied voltage
      on enantioseparation of acidic compounds, such as profens and aromatic carboxylic
      acids, was investigated. Two native alpha-amino acids, aspartic acid and glutamic
      acid, were enantioseparated. Fourteen tested compounds (including amino acids)
      were baseline resolved. Good selectivity of separation (alpha>1.09) was achieved.
      The migration order of ibuprofen and ketoprofen enantiomers was determined. The
      procedures were proposed for the analysis of flurbiprofen and warfarin in
      pharmaceuticals. Linearity was achieved in the concentration range of 4.0*10(-5)
      2.0*10(-3) M for flurbiprofen and 3.2*10(-6)-4.9*10(-6) M for warfarin. The
      detection limits were found to be about 1*10(-5) M for flurbiprofen and 1*10(-6)
      M for warfarin.

PMID- 21905046
TI  - Capillary electrophoresis and hollow fiber liquid-phase microextraction for the
      enantioselective determination of albendazole sulfoxide after biotransformation
      of albendazole by an endophytic fungus.
AB  - Hollow fiber liquid-phase microextraction and CE were applied for the
      determination of albendazole sulfoxide (ASOX) enantiomers in liquid culture
      medium after a fungal biotransformation study. The analytes were extracted from 1
      mL of liquid culture medium spiked with the internal standard (rac
      hydroxychloroquine) and buffered with 0.50 mol/L phosphate buffer, pH 10. The
      analytes were extracted into 1-octanol impregnated in the pores of the hollow
      fiber, and into an acid acceptor solution inside the polypropylene hollow fiber.
      The electrophoretic separations were carried out in 0.05 mol/L
      tris(hydroxymethyl)aminomethane buffer, pH 9.3, containing 3.0% w/v sulfated-beta
      CD (S-beta-CD) with a constant voltage of +15 kV and detection at 220 nm. The
      method was linear over the concentration range of 250-5000 ng/mL for each ASOX
      enantiomer. Within-day and between-day assay precision and accuracy for the
      analytes were studied at three concentration levels and the values of RSD% and
      relative error % were lower than 15%. The developed method was applied for the
      determination of ASOX after a biotransformation study employing the endophytic
      fungus Penicillium crustosum (VR4). This study showed that the endophytic fungus
      was able to metabolize the albendazole to ASOX enantioselectively. In addition,
      it was demonstrated that hollow fiber liquid-phase microextraction coupled to CE
      can be an excellent and environmentally friendly technique for the analysis of
      samples obtained in biotransformation studies.

PMID- 21905047
TI  - Separation of enantiomers of ephedrine by capillary electrophoresis using
      cyclodextrins as chiral selectors: comparative CE, NMR and high resolution MS
      studies.
AB  - The enantiomer migration order (EMO) of ephedrine was investigated in the
      presence of various CDs in CE. The molecular mechanisms of chiral recognition
      were followed for the ephedrine complexes with native alpha- and beta-CD and
      heptakis(2,3-di-O-acetyl-6-O-sulfo)-beta-CD (HDAS-beta-CD) by CE, NMR
      spectroscopy and high-resolution MS. Minor structural differences were observed
      between the complexes of ephedrine with alpha- and beta-CD although the migration
      order of enantiomers was opposite when these two CDs were applied as chiral
      selectors in CE. The EMO was also opposite between beta-CD and HDAS-beta-CD.
      Significant structural differences were observed between ephedrine complexes with
      the native CDs and HDAS-beta-CD. The latter CD was advantageous as chiral CE
      selector not only due to its opposite electrophoretic mobility compared with that
      of the cationic chiral analyte, but also primarily due to its enhanced chiral
      recognition ability towards the enantiomers of ephedrine.

PMID- 21905048
TI  - Chemical modification of proteins to improve the accuracy of their relative
      molecular mass determination by electrophoresis.
AB  - We studied the electrophoretic behavior of basic proteins (cytochrome c and
      histone III) and developed a carbamylation method that normalizes their
      electrophoretic size separation and improves the accuracy of their relative
      molecular mass determined electrophoretically. In capillary zone electrophoresis
      with cationic hitchhiking, native cytochrome c does not sufficiently bind
      cationic surfactants due to electrostatic repulsion between the basic protein and
      cationic surfactant. Carbamylation suppresses the strong positive charge of the
      basic proteins and results in more accurate relative molecular masses.

PMID- 21905049
TI  - Advances in the enantioseparation of beta-blocker drugs by capillary
      electromigration techniques.
AB  - beta-Blocker drugs or beta-adrenergic blocking agents are an important class of
      drugs, prescribed with great frequency. They are used for various diseases,
      particularly for the treatment of cardiac arrhythmias, cardioprotection after
      myocardial infarction (heart attack), and hypertension. Almost all beta-blocker
      drugs possess one or more stereogenic centers; however; only some of them are
      administered as single enantiomers. Since both enantiomers can differ in their
      pharmacological and toxicological properties, enantioselective analytical methods
      are required not only for pharmacodynamic and pharmacokinetic studies but also
      for quality control of pharmaceutical preparations with the determination of
      enantiomeric purity. In addition to the chromatographic tools, in recent years,
      capillary electromigration techniques (CE, CEC, and MEKC) have been widely used
      for enantioselective purposes employing a variety of chiral selectors, e.g. CDs,
      polysaccharides, macrocyclic antibiotics, proteins, chiral ion-paring agents,
      etc. The high separation efficiency, rapid analysi,s and low consumption of
      reagents of electromigration methods make them a very attractive alternative to
      the conventional chromatographic methods. In this review, the development and
      applications of electrodriven methods for the enantioseparation of beta-blocker
      drugs are reported. The papers concerning this topic, published from January 2000
      until December 2010, are summarised here. Particular attention is given to the
      coupling of chiral CE and CEC methods to MS, as this detector provides high
      sensitivity and selectivity.

PMID- 21905050
TI  - Local protein backbone folds determined by calculated NMR chemical shifts.
AB  - NMR chemical shifts (CSs: deltaN(NH), deltaC(alpha), deltaC(beta), deltaC',
      deltaH(NH), and deltaH(alpha)) were computed for the amino acid backbone
      conformers (alpha(L), beta(L), gamma(L), delta(L), epsilon(L), alpha(D),
      gamma(D), delta(D), and epsilon(D) [Perczel et al., J Am Chem Soc 1991, 113,
      6256]) modeled by oligoalanine structures. Topological differences of the
      extended fold were investigated on single beta-strands, hairpins with type I and
      II beta-turns, as well as double- and triple-stranded beta-sheet models. The so
      called "capping effect" was analyzed: residues at the termini of a homoconformer
      sequence unit usually have different CSs than the central residues of an
      adequately long homoconformer model. In heteroconformer sequences capping effect
      ruins the direct applicability of several chemical shift types (deltaH(NH),
      deltaC', and deltaN(NH)) for backbone structure determination of the parent
      residue. Experimental deltaH(alpha), deltaC(alpha), and deltaC(beta) values
      retrieved from protein database are in good agreement with the relevant computed
      data in the case of the common backbone conformers (alpha(L), beta(L), gamma(L),
      and epsilon(L)), even though neighboring residue effects were not accounted for.
      Experimental and computed DeltadeltaH(alpha)-DeltadeltaC(alpha),
      DeltadeltaH(alpha)-DeltadeltaC(beta), and DeltadeltaC(alpha)-DeltadeltaC(beta)
      maps give qualitatively the same picture, that is, the positions of the backbone
      conformers relative to each other are very similar. This indicates that the
      H(alpha), C(alpha), and C(beta) chemical shifts of alanine depend considerably on
      the backbone fold of the parent residue also in proteins. We provide tabulated
      CSs of the chiral amino acids that may predict the various structures of the
      residues.

PMID- 21905051
TI  - Mosaicism in clinical practice exemplified by prenatal diagnosis in
      retinoblastoma.

PMID- 21905052
TI  - Corpus callosum growth in normal and growth-restricted fetuses.
AB  - OBJECTIVE: The aim of this study was to characterize the normal ultrasonographic
      growth of the corpus callosum (CC) in normal and in growth-restricted fetuses
      throughout gestation. METHODS: This was a prospective cross-sectional study.
      Consecutive routine biometric measurements and fetal organ scans were obtained in
      patients undergoing elective fetal anatomical surveys or evaluation of the fetal
      growth between 16 to 33 weeks. Special attention was given to the CC of the fetal
      brain. In addition, we evaluated the growth of the CC in growth-restricted
      fetuses throughout pregnancy. RESULTS: Two hundred and fifty two normal fetuses
      were scanned between 16 and 36  weeks of gestation. A regression line of the CC
      was established through gestation and a second-degree correlation was found
      between gestational age and CC outer margin. Twenty four growth-restricted
      fetuses were also evaluated in which the growth of the CC was significantly below
      both the 25(th) and 50(th) percentiles in 77.3% and 95.5%, respectively, for the
      same gestational age. CONCLUSIONS: We provide nomograms for the ultrasonographic
      dimensions of the fetal CC that allows for prenatal diagnosis of abnormal
      dimensions of CC. The significance of abnormal CC growth in growth-restricted
      fetuses should be further evaluated.

PMID- 21905053
TI  - Conjoined twins pregnancies: experience with 36 cases from a single center.
AB  - OBJECTIVE: To review a single center's experience in the management of twin
      pregnancies with conjoined fetuses. METHODS: Retrospective study describing
      prenatal findings, delivery details, surgical treatment and perinatal outcome.
      RESULTS: The study included 36 twin pregnancies with conjoined twins seen over a
      period of 12 years in a single tertiary hospital: 69.4% were thoracopagus, 13.9%
      parapagus, 8.3% omphaloischiopagus 5.6% omphalopagus and 2.8% cephalopagus.
      Cardiac defects were present in 91.6% of twin pairs and associated malformations
      were present in 61.8% of the cases: limb abnormalities in 36.1%, abdominal wall
      defects in 25.0%, cleft lip and/or palate in 13.9% and congenital diaphragmatic
      hernia in 5.5%. Surgical separation was considered not feasible and prognosis
      lethal in 30 (83.3%) cases. Termination of pregnancy was performed in 12
      pregnancies of poor prognosis. Cesarean section was performed in all remaining
      cases. Five sets of twins underwent surgical separation and six children
      survived. Overall survival in our series was 8.3% and, among the livebirths,
      13.6%. CONCLUSION: Conjoined twin pregnancies should be referred to tertiary
      centers for detailed fetal anomaly and echocardiographic assessment to evaluate
      prognosis and determine the possibility of postnatal surgical separation.

PMID- 21905054
TI  - Ultrasound prognostic factors after laser surgery for twin-twin transfusion
      syndrome to predict survival at 6 months.
AB  - OBJECTIVE: To evaluate the significance of ultrasound findings, detected one or
      two weeks after laser surgery for twin-twin transfusion syndrome, in predicting
      the mortality at 6 months of age. METHODS: Ultrasound evaluation including fetal
      biometry, amniotic fluid volume estimation and Doppler examination was performed
      between 7 and 14 days after surgery for 181 cases. The presence of one or more
      effusions and single fetal death were also determined. Associations between
      ultrasound findings and mortality at 6 months of age were evaluated using
      multiple logistic regression analysis. RESULTS: Of the total 181 pairs, 145
      (80.1%) donor and 160 (88.1%) recipient twins survived in utero for more than 7
      days after surgery, and hence were included in the analysis. The survival rate at
      6 months was 66.9% for the donor and 80.7% for the recipient twins. Risk factors
      for death in the donor were the presence of severe intrauterine growth
      restriction and effusions. In recipients, elevation in the middle cerebral artery
      peak systolic velocity coincided with fetal death, but this occurred in only
      three cases. CONCLUSION: Ultrasound risk factors one week after surgery included
      severe intrauterine growth restrictions and effusions in the donor twins.

PMID- 21905057
TI  - Rapid and sensitive LC-MS/MS method for quantification of lamotrigine in human
      plasma: application to a human pharmacokinetic study.
AB  - A highly sensitive, specific and fully validated LC-MS/MS method as per general
      practices of industry has been developed for estimation of lamotrigine (LAM) with
      100 MUL of human plasma using flucanozole as an internal standard (IS). The API
      4000 LC-MS/MS was operated under the multiple reaction-monitoring mode using
      electrospray ionization. A simple liquid-liquid extraction process was used to
      extract LAM and IS from human plasma. The total run time was 2.0 min and the
      elution of LAM and IS occurred at 1.25 and 1.45 min; this was achieved with a
      mobile phase consisting of 0.1% formic acid-methanol (20:40:40, v/v) at a flow
      rate of 0.50 mL/min on a Discovery CN (50 * 4.6 mm, 5 um) column. The developed
      method was validated in human plasma with a lower limit of quantitation of 0.1
      ng/mL for LAM. A linear response function was established for the range of
      concentrations 0.1-1500 ng/mL (r > 0.998) for LAM. The intra- and inter-day
      precision values for LAM met the acceptance as per Food and Drug Administration
      guidelines. LAM was stable in the set of stability studies, viz. bench-top,
      autosampler and freeze-thaw cycles. The developed assay method was applied to an
      oral bioequivalence study in humans.

PMID- 21905055
TI  - Nephrotoxicity of hexachloro-1:3-butadiene in the male Hanover Wistar rat;
      correlation of minimal histopathological changes with biomarkers of renal injury.
AB  - Hexachloro-1:3-butadiene (HCBD) causes damage specifically to the renal proximal
      tubule in rats. In the present study, injury to the nephron of male Hanover
      Wistar rats was characterized at 24 h following dosing with HCBD in the range 5
      90 mg kg-1 to determine the most sensitive biomarkers of damage, that is, the
      biomarkers demonstrating significant changes at the lowest dose of HCBD, using a
      range of measurements in serum and urine, renal histopathology, and renal and
      hepatic gene expression. Histologically, kidney degeneration was noted at doses
      as low as 10 mg kg-1 HCBD. Significant changes in the hepatic and renal gene
      expression categories of xenobiotic metabolism and oxidative stress were observed
      at 5 mg kg-1 HCBD, and in the kidney alone, evidence of inflammation at 90 mg kg
      1 HCBD. Increases in the urinary excretion of alpha-glutathione S-transferase
      (alpha-GST) and kidney injury molecule-1 (KIM-1) were seen at 10 mg kg-1 HCBD,
      and increases in urinary excretion of albumin and total protein were evident at
      15 mg kg-1 HCBD. The most sensitive, noninvasive biomarkers of HCBD-induced renal
      toxicity in Hanover Wistar rats were urinary alpha-GST and KIM-1. Urinary albumin
      measurement is also recommended as, although it is not the most sensitive
      biomarker, together with alpha-GST, albumin showed the largest relative increase
      of all the biomarkers investigated, and the protein is easily measured.

PMID- 21905056
TI  - A clinical assay for the measurement of milrinone in plasma by HPLC mass
      spectrometry.
AB  - Milrinone is a bipyridine phosphodiesterase inhibitor with positive inotropic and
      vasodilatory effects. As interest in longer term use of intravenous therapy
      increases, it becomes essential to monitor its plasma concentration owing to a
      narrow therapeutic range, an increased half-life in renal failure and toxicity
      associated with high levels. A high-performance liquid chromatography (HPLC)
      method with mass (MS) detection using a triple quadrupole mass spectrometer is
      presented. The method was compared with the UV/HPLC method and validated
      according to current international guidelines. Coefficients of variation of less
      than 7.5% were obtained across the therapeutic range and 18.3% at 2.4 ng/mL, the
      lower limit of quantitation. Plasma from 13 cardiac surgery patients receiving
      standard intravenous doses of milrinone were measured. Eight patients achieved
      therapeutic milrinone levels within 3-4 h post start of infusion, one was
      borderline sub-therapeutic and four patients achieved levels that were above the
      upper limit of the therapeutic range and potentially toxic. This method offers
      high sensitivity, is rapid, easy to use and requires minimal amount of sample. We
      believe this method could become the reference procedure for clinical monitoring
      of milrinone and help to improve the safety of the use of this drug in patients
      with cardiac failure.

PMID- 21905058
TI  - HPLC-ICP-MS method development to monitor arsenic speciation changes by human gut
      microbiota.
AB  - Inorganic arsenic (iAs) has been classified as a type 1 carcinogen and has also
      been linked to several noncancerous health effects. Prior to 1995, the As(V)
      methylation pathway was generally considered to be a detoxification pathway, but
      cellular and animal studies involving MMA(III) (mono metyl arsonous acid) and
      DMA(III) (dimethyl arsinous acid) have indicated that their toxicities meet or
      exceed that of iAs, suggesting an activation process. In addition, thiolated
      arsenic metabolites were observed in urine after oral exposure of inorganic
      arsenic in some studies, for which the toxicological profile was not yet fully
      characterized in human cells. Studies have revealed that microorganisms from the
      gut environment are important contributors to arsenic speciation changes. This
      presystemic metabolism necessitates the development of protocols that enable the
      detection of not only inorganic arsenic species, but also pentavalent and
      trivalent methylated, thiolated arsenicals in a gastrointestinal environment. We
      aim to study the biotransformation of arsenic (As) using a Simulator of the Human
      Intestinal Microbial Ecosystem (SHIME). To be able to analyze the arsenicals
      resulting from biotransformation reactions occurring in this system, a method
      using liquid chromatography hyphenated to an inductively coupled plasma mass
      spectrometer (HPLC-ICP-MS) was developed. A Hamilton PRP-X100 anion exchange
      column was used. The method allowed separation, identification and quantification
      of As(III) (arsenite), As(V) (arsenate), DMA(V) (dimethylarsinicacid), MMA(V)
      (monomethylarsonicacid) and MMMTA (monomethylmonothioarsenate). Attempts to
      optimize the same method for also separating MMA(III) and DMA(III) did not
      succeed. These compounds could be successfully separated using a method based on
      the use of a Zorbax C18 column. The properties of the column, buffer strength, pH
      and polar nature of mobile phase were monitored and changed to optimize the
      developed methods. Linearity, sensitivity, precision, accuracy and resolution of
      both methods were checked. The combination of the two methods allowed successful
      quantification of arsenic species in suspensions sampled in vitro from the SHIME
      reactor or in vivo from the human colon and feces.

PMID- 21905059
TI  - Affiliative relationships and reciprocity among adult male bonnet macaques
      (Macaca radiata) at Arunachala Hill, India.
AB  - In captivity, male bonnet macaques (Macaca radiata) frequently express
      "friendship" toward one another, including affiliative behavior such as huddling,
      grooming, coalitionary support, and sitting in close proximity. The purpose of
      this study was to determine whether wild adult male bonnet macaques also express
      "friendship" by investigating whether or not (1) adult male bonnet macaques have
      affiliative social relationships with other males, (2) the strength of social
      relationships varies among dyads, (3) there is time-matched reciprocity in
      allogrooming among dyads, and if so, whether the level of reciprocity occurs
      within a bout of grooming, a day, or over 2 months (the limit of this study), and
      (4) a correlation exists between the strength of social relationships and
      dominance ranks among adult males. Focal samples totaling 150 hr on all seven
      adult males in one study group were conducted to record both agonistic and
      affiliative interactions. Agonistic interactions were used to construct a
      dominance hierarchy, whereas affiliative interactions (sitting in proximity to
      within 1 m with and without grooming) were used to quantify the existence and
      strength of social bonds within dyads. Results show that adult male bonnet
      macaques had differentiated affiliative relationships with other males in their
      group. There was little reciprocity of grooming within a bout of grooming or
      within a day, but greater reciprocity over the study period of 2 months. There
      was no correlation between dominance ranking distance and the strength of
      affiliative relationship within dyads; however, within dyads lower-ranking males
      groomed higher-ranking males more than vice versa. This study suggests that
      friendships in male bonnet macaques are characterized not by immediate tit-for
      tat reciprocal altruism, but by reciprocity over a longer time span, and that
      affiliative social relationships may be less constrained by agonistic
      relationships than is the case in more despotic species of macaques.

PMID- 21905060
TI  - Assessing the effects of cognitive experiments on the welfare of captive
      chimpanzees (Pan troglodytes) by direct comparison of activity budget between
      wild and captive chimpanzees.
AB  - We investigated the effects of cognitive experiments by direct comparison of
      activity budgets between wild and captive chimpanzees. One goal of captive
      management is to ensure that the activity budgets of captive animals are as
      similar as possible to those of their wild counterparts. However, such similarity
      has rarely been achieved. We compared the activity budget among three groups of
      chimpanzees: wild chimpanzees in Bossou (Guinea, n = 10), and captive chimpanzees
      who participated in cognitive experiments (experimental chimpanzees, n = 6) or
      did not participate in the experiments (nonexperimental chimpanzees, n = 6) at
      the Primate Research Institute (Japan). The experimental chimpanzees voluntarily
      participated in computer-controlled cognitive tasks and small pieces of fruits
      were provided as rewards. The data from captivity were obtained on the
      experimental days (weekdays) and nonexperimental days (weekends). In both study
      sites, we followed each chimpanzee from about 7 a.m. until the time when
      chimpanzees started to rest in the evening. The behaviors were recorded every 1
      min. The results showed that on weekdays, feeding time and resting time of the
      experimental chimpanzees were almost the same as those of wild chimpanzees.
      However, for the nonexperimental chimpanzees, feeding time was significantly
      shorter and resting time was longer than those of the wild chimpanzees. In
      contrast, no difference was found in feeding time or resting time of the two
      groups of captive chimpanzees on weekends. The results suggested that the
      cognitive experiments worked as an efficient method for food-based enrichment.

PMID- 21905061
TI  - Sex differences in the stone tool-use behavior of a wild population of burmese
      long-tailed macaques (Macaca fascicularis aurea).
AB  - We investigated sex differences in how Burmese long-tailed macaques (Macaca
      fascicularis aurea) used stone tools to open shelled food items along the shores
      of two islands in Laemson National Park, Thailand. Over a 2-week period in
      December 2009, we collected scan and focal samples on macaques when they were
      visible along the shores and mangroves. We found females used stones more often
      while feeding and used smaller tools than males. Females also processed sessile
      oysters more than males, whereas males processed unattached foods more than
      females. It was unclear which sex was overall more proficient at stone tool use,
      but males did perform significantly better at opening unattached food items with
      large pounding stones. Females also struck food items more times during tool-use
      bouts and at a faster rate, but no significant difference was found in average
      tool-use bout duration. Males processed foods slightly faster within a tool-use
      bout, but we were unable to detect a significant difference in the rate of food
      processing while foraging with tools. In summary females chipped open sessile
      oysters with an axing technique more than males, while males used larger stones
      to pound open unattached shelled food more often than females. Despite using
      pounding more than females, males also regularly utilized the axing technique on
      sessile oysters. Our results are the first assessment of sex differences in
      macaque stone tool use, providing a basis for comparison with tool use in other
      primates, and to nonfunctional forms of stone use in other macaques.

PMID- 21905062
TI  - Peaceful primates: affiliation, aggression, and the question of female dominance
      in a nocturnal pair-living lemur (Avahi occidentalis).
AB  - Affiliation/agonism and social dominance are central factors determining social
      organization in primates. The aim of our study is to investigate and describe,
      for the first time, the intersexual relations in a nocturnal and cohesive pair
      living prosimian primate, the western woolly lemur (Avahi occidentalis), and to
      determine to what extent phylogeny, activity mode, or the cohesiveness of pair
      partners shape the quality of social interactions. Six pairs of western woolly
      lemurs were radio-collared in the dry deciduous forest of northwestern
      Madagascar. More than 874 hr of focal animal sampling were conducted. All
      occurrences of social interactions involving a focal animal were recorded. The
      rate of affiliation between pair partners was significantly higher than the rate
      of agonism. Western woolly lemur pairs' interactions were extremely peaceful. All
      decided agonistic conflicts (N = 15) were exclusively initiated and won by the
      female. No female showed spontaneous submission toward her male partner. These
      results are in line with those of diurnal cohesive pair-living anthropoid
      primates. Findings support the hypothesis that social relations in pair-living
      primates are linked to the cohesiveness of pair partners in time and space
      irrespective of phylogeny and activity mode.

PMID- 21905063
TI  - Socialization strategies and disease transmission in captive colonies of nonhuman
      primates.
AB  - In captive research environments for nonhuman primates (NHP), social housing
      strategies are often in conflict with protocols designed to minimize disease
      transmission. This is particularly true in breeding colonies, and is especially
      relevant when attempting to eliminate specific pathogens from a population of
      primates. Numerous strategies have been used to establish such specific pathogen
      free (SPF) breeding colonies (primarily of macaques), ranging from nursery
      rearing of neonates to single housing of socially reared yearlings to the rearing
      of infants in large social groups. All these strategies attempt to balance the
      effects of the chosen socialization strategy on parameters related to disease
      transmission, including the ultimate elimination of the target pathogens. Such
      strategies may affect the overall disease states of NHP breeding colonies through
      selective breeding processes. This can occur either by creating subpopulations of
      animals that do not have target diseases (SPF colonies), but may have other
      issues; or by creating situations in which the "best" animals are sold and the
      breeding colony is stocked with animals that may be more disease susceptible than
      those that were sold. The disease states of NHP research colonies also may be
      affected by selective utilization programs, in which animals removed from the
      breeding colony for health/behavior reasons, are preferentially chosen for use in
      scientific investigations. Such utilization criteria raise the question of
      whether ideal subjects are being chosen for use in research. Finally, captive
      primate colonies, where both socialization and disease states are intensely
      managed, may provide opportunities for those testing predictions from models of
      the interactions of socialization and disease transmission in the evolution of
      wild populations of NHP. This would be especially true for some extreme
      conditions of these disease ecology models, given the exceedingly high social
      densities and levels of pathogen control that exist in many captive nonhuman
      primate colonies.

PMID- 21905064
TI  - The benefit of stratification in clinical trials revisited.
AB  - Stratification is common in clinical trials because it can reduce the variance of
      the estimated treatment effect. The traditional demonstration of variance
      reduction relies on the assumption of stratum sizes being fixed quantities.
      However, in practice, to speed up enrollment, and to obtain a study population
      with a similar distribution as the overall population, the stratum sizes are
      allowed to vary. Under the condition that the total sample size is fixed and that
      the stratum sizes have a multinomial distribution, the criterion changes for
      achieving a reduction in variance. The relationship between the stratified and
      unstratified variances is established and shown to be approximately the same for
      prestratified and post-stratified trials. It is demonstrated why stratification
      may actually increase the variance compared with no stratification even when the
      mean square error is reduced on account of stratification. Data from a real
      clinical trial will be used for illustration. The benefit attributed to
      stratification needs to be re-examined in light of the findings presented,
      particularly given its widespread use.

PMID- 21905065
TI  - Identifying influential observations in Bayesian models by using Markov chain
      Monte Carlo.
AB  - In statistical modelling, it is often important to know how much parameter
      estimates are influenced by particular observations. An attractive approach is to
      re-estimate the parameters with each observation deleted in turn, but this is
      computationally demanding when fitting models by using Markov chain Monte Carlo
      (MCMC), as obtaining complete sample estimates is often in itself a very time
      consuming task. Here we propose two efficient ways to approximate the case
      deleted estimates by using output from MCMC estimation. Our first proposal, which
      directly approximates the usual influence statistics in maximum likelihood
      analyses of generalised linear models (GLMs), is easy to implement and avoids any
      further evaluation of the likelihood. Hence, unlike the existing alternatives, it
      does not become more computationally intensive as the model complexity increases.
      Our second proposal, which utilises model perturbations, also has this advantage
      and does not require the form of the GLM to be specified. We show how our two
      proposed methods are related and evaluate them against the existing method of
      importance sampling and case deletion in a logistic regression analysis with
      missing covariates. We also provide practical advice for those implementing our
      procedures, so that they may be used in many situations where MCMC is used to fit
      statistical models.

PMID- 21905067
TI  - Bayesian adaptive clinical trials: a dream for statisticians only?
AB  - Adaptive or 'flexible' designs have emerged, mostly within frequentist
      frameworks, as an effective way to speed up the therapeutic evaluation process.
      Because of their flexibility, Bayesian methods have also been proposed for Phase
      I through Phase III adaptive trials; however, it has been reported that they are
      poorly used in practice. We aim to describe the international scientific
      production of Bayesian clinical trials by investigating the actual development
      and use of Bayesian 'adaptive' methods in the setting of clinical trials. A
      bibliometric study was conducted using the PubMed and Science Citation Index
      Expanded databases. Most of the references found were biostatistical papers from
      various teams around the world. Most of the authors were from the US, and a large
      proportion was from the MD Anderson Cancer Center (University of Texas, Houston,
      TX). The spread and use of these articles depended heavily on their topic, with
      3.1% of the biostatistical articles accumulating at least 25 citations within 5
      years of their publication compared with 15% of the reviews and 32% of the
      clinical articles. We also examined the reasons for the limited use of Bayesian
      adaptive design methods in clinical trials and the areas of current and future
      research to address these challenges. Efforts to promote Bayesian approaches
      among statisticians and clinicians appear necessary.

PMID- 21905068
TI  - A mixture model with random-effects components for classifying sibling pairs.
AB  - In healthy aging research, typically multiple health outcomes are measured,
      representing health status. The aim of this paper was to develop a model-based
      clustering approach to identify homogeneous sibling pairs according to their
      health status. Model-based clustering approaches will be considered on the basis
      of linear mixed effect model for the mixture components. Class memberships of
      siblings within pairs are allowed to be correlated, and within a class the
      correlation between siblings is modeled using random sibling pair effects. We
      propose an expectation-maximization algorithm for maximum likelihood estimation.
      Model performance is evaluated via simulations in terms of estimating the correct
      parameters, degree of agreement, and the ability to detect the correct number of
      clusters. The performance of our model is compared with the performance of
      standard model-based clustering approaches. The methods are used to classify
      sibling pairs from the Leiden Longevity Study according to their health status.
      Our results suggest that homogeneous healthy sibling pairs are associated with a
      longer life span. Software is available for fitting the new models.

PMID- 21905069
TI  - Bone marrow trephine biopsy findings in acute promyelocytic leukemia.

PMID- 21905071
TI  - Paper linking XMRV to chronic fatigue syndrome stirs controversy.

PMID- 21905072
TI  - Richard Olney's perspective as physician-scientist and patient.

PMID- 21905074
TI  - On human disease and animal models.

PMID- 21905066
TI  - A framework for quantifying net benefits of alternative prognostic models.
AB  - New prognostic models are traditionally evaluated using measures of
      discrimination and risk reclassification, but these do not take full account of
      the clinical and health economic context. We propose a framework for comparing
      prognostic models by quantifying the public health impact (net benefit) of the
      treatment decisions they support, assuming a set of predetermined clinical
      treatment guidelines. The change in net benefit is more clinically interpretable
      than changes in traditional measures and can be used in full health economic
      evaluations of prognostic models used for screening and allocating risk reduction
      interventions. We extend previous work in this area by quantifying net benefits
      in life years, thus linking prognostic performance to health economic measures;
      by taking full account of the occurrence of events over time; and by considering
      estimation and cross-validation in a multiple-study setting. The method is
      illustrated in the context of cardiovascular disease risk prediction using an
      individual participant data meta-analysis. We estimate the number of
      cardiovascular-disease-free life years gained when statin treatment is allocated
      based on a risk prediction model with five established risk factors instead of a
      model with just age, gender and region. We explore methodological issues
      associated with the multistudy design and show that cost-effectiveness
      comparisons based on the proposed methodology are robust against a range of
      modelling assumptions, including adjusting for competing risks.

PMID- 21905075
TI  - Microglial activation and traumatic brain injury.

PMID- 21905076
TI  - Improving the accuracy of perfusion imaging in acute ischemic stroke.

PMID- 21905077
TI  - Turning skin into brain: using patient-derived cells to model X-linked
      adrenoleukodystrophy.

PMID- 21905078
TI  - Stem cell technology for neurodegenerative diseases.
AB  - Over the past 20 years, stem cell technologies have become an increasingly
      attractive option to investigate and treat neurodegenerative diseases. In the
      current review, we discuss the process of extending basic stem cell research into
      translational therapies for patients suffering from neurodegenerative diseases.
      We begin with a discussion of the burden of these diseases on society,
      emphasizing the need for increased attention toward advancing stem cell
      therapies. We then explain the various types of stem cells utilized in
      neurodegenerative disease research, and outline important issues to consider in
      the transition of stem cell therapy from bench to bedside. Finally, we detail the
      current progress regarding the applications of stem cell therapies to specific
      neurodegenerative diseases, focusing on Parkinson disease, Huntington disease,
      Alzheimer disease, amyotrophic lateral sclerosis, and spinal muscular atrophy.
      With a greater understanding of the capacity of stem cell technologies, there is
      growing public hope that stem cell therapies will continue to progress into
      realistic and efficacious treatments for neurodegenerative diseases.

PMID- 21905079
TI  - Neuron-restrictive silencer factor-mediated hyperpolarization-activated cyclic
      nucleotide gated channelopathy in experimental temporal lobe epilepsy.
AB  - OBJECTIVE: Enduring, abnormal expression and function of the ion channel
      hyperpolarization-activated cyclic adenosine monophosphate gated channel type 1
      (HCN1) occurs in temporal lobe epilepsy (TLE). We examined the underlying
      mechanisms, and investigated whether interfering with these mechanisms could
      modify disease course. METHODS: Experimental TLE was provoked by kainic acid
      induced status epilepticus (SE). HCN1 channel repression was examined at mRNA,
      protein, and functional levels. Chromatin immunoprecipitation was employed to
      identify the transcriptional mechanism of repressed HCN1 expression, and the
      basis for their endurance. Physical interaction of the repressor, NRSF, was
      abolished using decoy oligodeoxynucleotides (ODNs). Video/electroencephalographic
      recordings were performed to assess the onset and initial pattern of spontaneous
      seizures. RESULTS: Levels of NRSF and its physical binding to the Hcn1 gene were
      augmented after SE, resulting in repression of HCN1 expression and HCN1-mediated
      currents (I(h) ), and reduced I(h) -dependent resonance in hippocampal CA1
      pyramidal cell dendrites. Chromatin changes typical of enduring, epigenetic gene
      repression were apparent at the Hcn1 gene within a week after SE. Administration
      of decoy ODNs comprising the NRSF DNA-binding sequence (neuron restrictive
      silencer element [NRSE]), in vitro and in vivo, reduced NRSF binding to Hcn1,
      prevented its repression, and restored I(h) function. In vivo, decoy NRSE ODN
      treatment restored theta rhythm and altered the initial pattern of spontaneous
      seizures. INTERPRETATION: Acquired HCN1 channelopathy derives from NRSF-mediated
      transcriptional repression that endures via chromatin modification and may
      provide insight into the mechanisms of a number of channelopathies that coexist
      with, and may contribute to, the conversion of a normal brain into an epileptic
      one.

PMID- 21905081
TI  - A new mitochondria-related disease showing myopathy with episodic hyper-creatine
      kinase-emia.
AB  - OBJECTIVE: To elucidate the relationship between mitochondrial DNA (mtDNA)
      alterations and a mitochondrial disease with a distinct combination of
      characteristic symptoms, namely episodic hyper-creatine kinase (CK)-emia and mild
      myopathy. METHODS: We selected 9 patients with mtDNA np8291 alteration from 586
      patients suspected to have a mitochondrial disease, and assessed them clinically,
      pathologically, and genetically. These 9 patients had undiagnosed mitochondrial
      myopathy with episodic hyper-CK-emia, all showing similar symptoms and
      progression. RESULTS: Patients had mild muscle weakness and episodic hyper-CK
      emia triggered by infections or drugs. Five of 9 patients were initially
      diagnosed with other conditions, such as myasthenia gravis, polymyositis, viral
      myositis, and drug-induced myopathy, because these conditions were acute or
      subacute, and 9 patients showed the same 16 mtDNA alterations, which have been
      reported to be nonpathological polymorphisms. Muscle biopsy revealed ragged-red
      fibers, highly expressed succinate dehydrogenase staining fibers, and cytochrome
      c oxidase-deficient fibers. Because their mitochondrial sequence data was almost
      the same, and 9 patients live in widely separated cities in Japan, the
      alterations may have arisen from a single source. INTERPRETATION: These findings
      suggest that mild myopathy with episodic hyper-CK-emia associated with some of
      the 16 mtDNA alterations or at least with their mitochondria, could be a novel
      mitochondrial disease. Therefore, we propose that this disease be named as
      "mitochondrial myopathy with episodic hyper-CK-emia (MIMECK)." These alterations
      could work concomitantly and probably modify the impact of medications or other
      environmental factors. We believe these findings provide an insight into a novel
      aspect of mitochondrial disease pathogenesis.

PMID- 21905080
TI  - White matter lesions defined by diffusion tensor imaging in older adults.
AB  - OBJECTIVE: The cellular and molecular mechanisms underlying magnetic resonance
      imaging-defined white matter (WM) changes associated with age-related cognitive
      decline remain poorly defined. We tested the hypothesis that WM lesions in older
      adults, defined by diffusion tensor imaging (DTI), arise in the setting of
      vascular brain injury (VBI) and are characterized by increased free radical
      injury and aberrant oligodendrocyte lineage (OL) cell response to injury.
      METHODS: We undertook a multimodal analysis of prefrontal cortex (PFC) WM from 25
      autopsies derived from a population-based cohort where VBI and Alzheimer disease
      (AD) frequently coincide. Ex vivo high field strength DTI measurements of
      fractional anisotropy (FA), apparent diffusion coefficient, and axial and radial
      (D(?) ) diffusivity were measured at high magnetic field strength (11.7T) and
      analyzed relative to quantitative in vivo biomarkers of free radical injury, an
      OL-specific marker Olig2, and histologic evaluation of hyaluronan (HA), an
      inhibitor of OL maturation. RESULTS: Coincident AD and VBI showed significant
      association with lower FA and a robust relationship between decreasing FA and
      increasing D(?) . Free radical injury to docosahexaenoate and adrenate in PFC WM
      was significantly elevated in cases with VBI independent of AD, and was inversely
      correlated with FA. Similarly, increased density of Olig2-immunoreactive cells in
      PFC WM was significantly associated with VBI independent of AD and colocalized
      with regions enriched in HA. INTERPRETATION: DTI-defined PFC WM lesions in older
      individuals are characterized by free radical injury to myelin and neuroaxonal
      elements that coincides with pronounced expansion of the pool of OL cells in HA
      rich regions.

PMID- 21905082
TI  - Intrathymic Epstein-Barr virus infection is not a prominent feature of myasthenia
      gravis.
AB  - Lymph node-type T- and B-cell infiltrates with germinal centers are
      characteristic features of the hyperplastic thymus in early onset myasthenia
      gravis (EOMG).Epstein-Barr virus (EBV) infection confers survival advantages on B
      cells, and has recently been implicated in tertiary lymphoid tissue formation in
      EOMG. We evaluated the frequency of intrathymic EBV-infected B-lineage cells and
      antiviral immune responses in treatment-naive patients with EOMG. Real-time
      polymerase chain reaction was performed to quantify the content of genomic EBV
      DNA (BamHI-W repeat region) in thymic cell suspensions. Serial paraffin sections
      of EOMG thymi were analyzed for the presence of EBV-encoded RNA by in situ
      hybridization and for viral gene expression by immunohistochemistry. Humoral and
      cellular immune responses to viral antigens were quantified by enzyme-linked
      immunosorbent assay and flow cytometry-based intracellular cytokine staining. We
      detected minimal levels of viral DNA-corresponding to single viral genomes-in
      only 6 of 16 hyperplastic EOMG thymi, indicating extreme rarity of viral copy
      numbers in the investigated thymic samples. That was confirmed by similar rarity
      of EBV-encoded RNA and viral proteins identified in thymic sections. Furthermore,
      EBV-specific T- and B-cell responses were unchanged in patients with EOMG. These
      findings do not support an etiologic role for EBV in the initiation of EOMG.

PMID- 21905083
TI  - Lack of evidence for Epstein-Barr virus infection in myasthenia gravis thymus.
AB  - A role for Epstein-Barr virus (EBV) in myasthenia gravis pathogenesis has been
      suggested recently. Using in situ hybridization for the detection of the EBV
      encoded RNAs and EBNA1-specific immunohistochemistry, we found no latently
      infected cells in a series of thymus specimens from patients with myasthenia
      gravis showing lymphofollicular thymitis. In addition, using immunohistochemistry
      and an antibody specific for the viral immediate early protein BZLF1, no evidence
      of lytic EBV infection was seen in these cases. Our results therefore do not
      support a direct role of thymic EBV infection in the pathogenesis of myasthenia
      gravis.

PMID- 21905084
TI  - Epstein-Barr virus in myasthenia gravis thymus: a matter of debate.

PMID- 21905085
TI  - The effect of atherosclerosis-induced chronic bladder ischemia on bladder
      function in the rat.
AB  - AIMS: To develop a rat model of atherosclerosis-induced chronic bladder ischemia
      and investigate the effect of chronic bladder ischemia on voiding behavior and
      bladder function. METHODS: Adult male rats were divided into three groups. The
      arterial injury (AI) group underwent endothelial injury of the iliac arteries and
      received a 2% cholesterol diet. The sham group underwent sham operation and
      received a 2% cholesterol diet. The control group received a regular diet. After
      8 weeks, a metabolic cage study and cystometry were performed without anesthesia.
      Bladder blood flow was measured using a laser Doppler blood flowmeter.
      Histological examination of the iliac arteries and the bladder was performed. The
      bladder was also processed for immunohistochemical staining of oxidative stress
      markers. RESULTS: The metabolic cage study showed that in the AI group, voiding
      frequency significantly increased while voided volume significantly decreased.
      Cystometry showed that the frequency of reflex bladder contractions was
      significantly higher in the AI group. Filling-induced decrease in bladder blood
      flow was the greatest in the AI group. Histological study showed that in the AI
      group alone, atherosclerotic occlusion occurred in the iliac arteries as well as
      in the downstream bladder microvessels. Oxidative stress marker positive cells
      were more prevalent in the AI bladder than in the other bladders. CONCLUSIONS:
      Combined with a high-cholesterol diet, endothelial injury of iliac arteries
      induced arterial occlusive disease in the downstream vessels and consequent
      bladder ischemia in rats. This model of chronic bladder ischemia showed detrusor
      overactivity manifested as an increase in voiding frequency.

PMID- 21905086
TI  - Evaluation of an experimental urodynamic platform to identify treatment effects:
      a randomized, placebo-controlled, crossover study in patients with overactive
      bladder.
AB  - AIMS: To evaluate a urodynamic platform designed to identify treatment effects in
      small numbers of patients after a short duration of treatment using a medication
      with known efficacy in overactive bladder (OAB). METHODS: Twenty women with OAB
      were randomized in a crossover study with 7-day treatment periods with either
      tolterodine 4 mg long-acting (LA) or placebo and 7-day washout. Patients
      underwent urodynamic study (UDS) at baseline, 4-hr post-dose on Day 1 (PD1) and 4
      hr post-dose on Day 7 (PD7) in each treatment period. The primary endpoint was
      the change from baseline in volume at maximum cystometric capacity (MCC) at PD7.
      As a result of dosing errors, some patients allocated to tolterodine in Period 1
      mistakenly received placebo on Day 7. The data from the time points at which
      patients were dosed incorrectly were excluded from the per protocol (PP)
      analysis. RESULTS: The PP and intent to treat (ITT) mean increase in volume at
      MCC on PD7 for tolterodine compared with placebo was 28.9% (P = 0.038, one-sided)
      and 23.2% (P = 0.008, one-sided), respectively. The PD7 mean increase in volume
      at first desire to void was 36.5% (P = 0.054, PP) and 40.3% (P = 0.008, ITT). No
      volume endpoint at PD1 was statistically significant. Of all the endpoints, MCC
      was the least variable. CONCLUSIONS: This crossover design was able to detect a
      clinically meaningful and statistically significant treatment effect consistent
      with the previous reports of tolterodine. Despite multiple urodynamics per
      patient, the study was able to recruit quickly. This model is valuable for
      evaluating therapeutic effects for existing and novel treatments for OAB.

PMID- 21905087
TI  - Developing a new treatment device: how to get an idea to the marketplace.
AB  - A good idea does not inevitably lead to successful innovation; it needs
      additional "drivers" and coherent activity of a specialized team. The initial
      idea needs proof-of-concept and prototype testing. Alongside, market review must
      anticipate future need and competitors, and ensure that no current patents are
      infringed. The likelihood that reimbursement will be secured and that health
      systems will "adopt" the device has to be considered. Intellectual property (IP)
      protection is needed to maintain sole rights to exploit the core concept. Non
      disclosure agreements (NDA) should be put in place, and commercial considerations
      should be remembered before any disclosure in the public domain, including
      publications. Prospective business partners will review the concept from many
      perspectives, including stage of device development, effective IP protection, any
      clinical trial evidence, and whether the device aligns with their business
      strategy. Royalties arising from sales of a marketed device are distributed to
      all parties contributing to its development; the party bearing the greater
      financial burden of developing the final product will gain the greater share of
      royalties. The innovator's employer will have a call on proceeds if the idea
      arose in the course of employment. All stages of development require fastidious
      documentation to meet requirements of the regulatory authorities responsible for
      permitting use in patients. Specific regulatory requirements depend on which
      region(s) of the world the device will be marketed in. This review explains all
      stages of the innovation pathway from concept to adoption, giving practical
      advice and signposting expertise relevant to each stage.

PMID- 21905088
TI  - The use of botulinum toxin in benign prostatic hyperplasia.
AB  - The injection of Botulinum toxin type A (BoNT/A) into the prostate is a minimally
      invasive alternative treatment for lower urinary tract symptoms. To summarize the
      action mechanisms of BoNT/A on experimental animals and to analyze its
      effectiveness according to published clinical studies, we located 24 papers on
      the treatment of HBP with BoNT/A. The doses applied ranged from 100 (OnabotA) to
      600 U (OnabotA and AbobotA). The IPSS score presented a mean post-treatment
      reduction, for all series, of 10.8 + 2.66 points. Other significant results
      included the overall mean reduction in QoL score of 2.1 +/- 0.62 points, and the
      pre and post-treatment differences in prostate volume (22.43 +/- 20.2 cm(3)),
      post-voiding residue (76.77 + 51.72 cm(3)) and PSA (1.15 + 0.93 ng/ml). However,
      only two clinical trials were on sufficient quality to be selected for meta
      analysis, and it was observed that the difference of the means, pre- and post
      treatment of maximum flow, prostate volume, IPSS and PSA were not statistically
      significant (P = 0.18). Neither was there any statistically significant
      difference between pre- and post-treatment post-voiding residue (P = 0.65). In
      conclusion, BoNT/A alleviates lower urinary tract symptoms due to HBP, but
      different studies present considerable variations regarding the dose
      administered, inclusion criteria and follow-up time, as well as poorly defined
      retreatment, losses to follow up and, above all, a high degree of variability in
      the communication of results (with large standard deviations). In consequence,
      further clinical trials are needed.

PMID- 21905089
TI  - Construction and test of an artificial uterus for ex situ development of shark
      embryos.
AB  - An artificial uterus (AU) was constructed from clear and opaque acrylic and life
      support and monitoring systems were attached. The dwarf ornate wobbegong shark
      (Orectolobus ornatus) was used to test the AU because recent research has shown
      that during pregnancy the uterine fluid composition changes with mid- to late
      term embryos immersed in seawater. An artificial uterine fluid comprising
      filtered, autoclaved seawater was placed in the AU. Eight, sexually mature female
      O. ornatus were captured from the wild and held in captivity. Subsequent
      ultrasound examinations confirmed pregnancy in three of these females. Six late
      term embryos (three males and three females) were removed surgically from one
      euthanized female and placed in the AU. Their condition was monitored for 18 days
      before "birth" on September 26, 2008. The subsequent survival and growth of the
      AU pups was compared with naturally born wobbegong pups in captivity over a 140
      day monitoring period. The development in the AU did not have detrimental effects
      as there was no postpartum mortality and there were marked increases in total
      length and weight that did not differ significantly between the two groups.

PMID- 21905090
TI  - Construction of diploid zygotes by interallelic complementation of ade6 in
      Schizosaccharomyces japonicus.
AB  - The construction of diploid cells eases genetic analysis in haploid genetic
      systems because diploid cells allow for the characterization of essential genes.
      Here, we report the construction of diploid cells using ade6 point mutants that
      suppress each other via interallelic complementation in the fission yeast
      Schizosaccharomyces japonicus var japonicus (Sz. japonicus). We constructed an
      ade6-domK mutant in addition to the previously described ade6-domE. Phenotypes of
      both mutants exhibited adenine auxotrophy and red colonies. The mutations
      complemented the phenotypes in a mutually dependent manner. Diploid zygotes, in
      which the two mutations were introduced simultaneously into the same cells, were
      isolated by selecting for adenine independence. Such diploid cells are apparently
      larger in size than haploid cells, yet have a similar nuclear/cytoplasmic ratio,
      and thus the nuclear size control that has been reported in Sz. pombe is also
      present in Sz. japonicus.

PMID- 21905092
TI  - Growth of a tropical marine yeast Yarrowia lipolytica NCIM 3589 on bromoalkanes:
      relevance of cell size and cell surface properties.
AB  - Yarrowia lipolytica 3589, a tropical marine yeast, grew aerobically on a broad
      range of bromoalkanes varying in carbon chain length and differing in degree and
      position of bromide group. Amongst the bromoalkanes studied, viz. 2-bromopropane
      (2-BP), 1-bromobutane (1-BB), 1,5-dibromopentane (1,5-DBP) and 1-bromodecane (1
      BD), the best utilized was 1-BD, with a maximal growth rate (MU(max) ) of 0.055 h
      1 and an affinity ratio (MU(max) /K(s) ) of 0.022. Utilization of these
      bromoalkanes as growth substrates was associated with a concomitant release of
      bromide (8202.9 um) and cell mass (36 * 109 cells/ml), occurring maximally on 1
      BD. Adherence of yeast cells to these hydrophobic bromoalkanes was observed
      microscopically, with an increase in cell size and surface hydrophobicity. The
      maximal cell diameter was for 1-BD (4.66 um), resulting in an increase in the
      calculated cell surface area (68.19 um2) and sedimentation velocity (1.31 um/s).
      Cell surface hydrophobicity values by microbial adhesion to solvents (MATS)
      analysis for yeasts grown on bromoalkanes and glucose were significantly high,
      i.e. >80%. Similarly, water contact angles also indicate that the cell surface of
      yeast cells grown in glucose possess a relatively more hydrophilic cell surface
      (theta = 49.1 degrees ), whereas cells grown in 1-BD possess a more hydrophobic
      cell surface (theta = 90.7 degrees ). No significant change in emulsification
      activity or surface tension was detected in the cell-free supernatant. Thus
      adherence to the bromoalkane droplets by an increase in cell size and surface
      hydrophobicity leading to debromination of the substrate might be the strategy
      employed in bromoalkane utilization and growth by Y. lipolytica 3589.

PMID- 21905093
TI  - DhARO4 induction and tyrosine nitration in response to reactive radicals
      generated by salt stress in Debaryomyces hansenii.
AB  - It has been previously reported that growth of Debaryomyces hansenii in 2 M NaCl
      induced the expression of ARO4. This gene codifies for DhAro4p, involved in the
      synthesis of the amino acid tyrosine. In this work we studied the activity of
      DhAro4p upon salt stress; a higher activity was observed in cells grown with 2 M
      NaCl, but tyrosine levels were not increased. On the other hand, the addition of
      tyrosine to the saline medium significantly enhanced the growth of D. hansenii.
      It was found that the oxidized form of tyrosine, 3-nitrotyrosine, increased in
      the presence of salt. Since NaCl protects against oxidative stress in D. hansenii
      (Navarrete et al., 2009), we propose that a protective pathway is the de novo
      synthesis of tyrosine and its immediate oxidation to 3-nitrotyrosine to
      counteract oxidative stress generated by salt stress, so we measured the
      production of reactive oxygen species (ROS) and nitric oxide (NO-) in D. hansenii
      after growing in 2 M NaCl. Results showed the presence of NO- and the increased
      production of ROS; this is probably due to an increased respiratory activity in
      the cells grown in the presence of salt. Our results demonstrate that upon salt
      stress D hansenii responds to oxidative stress via the transcriptional activation
      of specific genes such as DhARO4.

PMID- 21905091
TI  - Substrate analysis of the Pneumocystis carinii protein kinases PcCbk1 and PcSte20
      using yeast proteome microarrays provides a novel method for Pneumocystis
      signalling biology.
AB  - Pneumocystis carinii (Pc) undergoes morphological transitions between cysts and
      trophic forms. We have previously described two Pc serine/threonine kinases,
      termed PcCbk1 and PcSte20, with PcSte20 belonging to a family of kinases involved
      in yeast mating, while PcCbk1 is a member of a group of protein kinases involved
      in regulation of cell cycle, shape, and proliferation. As Pc remains genetically
      intractable, knowledge on specific substrates phosphorylated by these kinases
      remains limited. Utilizing the phylogenetic relatedness of Pc to Saccharomyces
      cerevisiae, we interrogated a yeast proteome microarray containing >4000 purified
      protein based peptides, leading to the identification of 18 potential PcCbk1 and
      15 PcSte20 substrates (Z-score > 3.0). A number of these potential protein
      substrates are involved in bud site selection, polarized growth, and response to
      mating alpha factor and pseudohyphal and invasive growth. Full-length open
      reading frames suggested by the PcCbk1 and PcSte20 protoarrays were amplified and
      expressed. These five proteins were used as substrates for PcCbk1 or PcSte20,
      with each being highly phosphorylated by the respective kinase. Finally, to
      demonstrate the utility of this method to identify novel PcCbk1 and PcSte20
      substrates, we analysed DNA sequence data from the partially complete Pc genome
      database and detected partial sequence information of potential PcCbk1 kinase
      substrates PcPxl1 and PcInt1. We additionally identified the potential PcSte20
      kinase substrate PcBdf2. Full-length Pc substrates were cloned and expressed in
      yeast, and shown to be phosphorylated by the respective Pc kinases. In
      conclusion, the yeast protein microarray represents a novel crossover technique
      for identifying unique potential Pc kinase substrates.

PMID- 21905094
TI  - The effect of 90 day administration of a high dose vitamin B-complex on work
      stress.
AB  - OBJECTIVE: Occupational stress is increasing in Western societies and the impact
      is significant at a personal, organisational and community level. The present
      study examined for the first time the efficacy of 3 months administration of two
      forms of high dose vitamin B complex on mood and psychological strain associated
      with chronic work stress. METHOD: Sixty participants completed the 3-month,
      double-blind, randomised, placebo-controlled trial in which personality, work
      demands, mood, anxiety and strain were assessed. RESULTS: After individual
      differences in personality and work demands were statistically controlled, the
      vitamin B complex treatment groups reported significantly lower personal strain
      and a reduction in confusion and depressed/dejected mood after 12 weeks. There
      were no treatment-related changes in other measures of mood and anxiety.
      DISCUSSION: The results of the study are consistent with two previous studies
      examining multivitamin supplementation and personal (non-work) feelings of strain
      and suggestive of significant decreases in the experience of workplace stress
      after 90 day supplementation of a B multivitamin. CONCLUSION: Given the direct
      and indirect costs of workplace stress, these findings point to the utility of a
      cost-effective treatment for the mood and psychological strain effects of
      occupational stress. These findings may have important personal health,
      organisational and societal outcomes given the rising cost and incidence of
      workplace stress.

PMID- 21905095
TI  - PET imaging of brain amyloid in dementia: a review.
AB  - OBJECTIVE: To review the rapidly expanding literature of amyloid PET imaging with
      particular attention to Pittsburgh compound-B (PIB) in Alzheimer's disease (AD),
      dementia with Lewy bodies (DLB), fronto-temporal dementia (FTD), mild cognitive
      impairment (MCI) and cognitively normal volunteers. DESIGN: Literature searches
      were performed using Medline up to February 2010. Individual articles were then
      examined for additional references not revealed by automated searches. This
      yielded 79 articles whose abstracts were read by the authors to select key
      papers. RESULTS: Amyloid deposition assessed using PIB-PET is significantly
      elevated in AD and DLB compared to controls and those with FTD. In MCI, uptake is
      often intermediate between AD and normal ageing, and excessive amyloid burden in
      non-demented individuals with MCI are likely to represent high-risk cases.
      Amyloid deposition appears to be an early event, and as dementia progresses
      clinical decline seems to be more associated with neurodegeneration than amyloid
      burden. CONCLUSIONS: PIB-PET imaging is a sensitive and specific marker for
      underlying Abeta amyloid deposition and represents an important investigative
      tool for examining the relationship between amyloid burden, clinical symptoms and
      structural and functional changes in dementia. Amyloid imaging may also be useful
      for selecting patients for anti-amyloid therapies. However, studies have
      identified PIB-positive cases in otherwise healthy older individuals (10-30%),
      limiting diagnostic specificity. Development of biomarkers for investigating
      other aspects of dementia pathology, i.e. soluble Abeta, tau, synuclein and brain
      inflammation would further inform our understanding and assist in studying
      disease-modifying and preventive treatments in dementia.

PMID- 21905096
TI  - A systematic review of the effects of physical activity on physical functioning,
      quality of life and depression in older people with dementia.
AB  - BACKGROUND: Depression is common in older people with dementia. Physical activity
      is effective in reducing depression in adults but there is limited evidence about
      its effectiveness in people with dementia. DESIGN AND METHODS: A systematic
      review and partial meta-analysis of physical activity interventions in people
      with dementia is reported. We searched eight databases for English language
      papers and reference lists of relevant papers. Included studies reported a
      physical activity intervention lasting at least 12 weeks in which participants
      were older and had a diagnosis of dementia. Studies compared the intervention
      with a non-active or a no-intervention control and reported at least one outcome
      related to physical function, quality of life or depression. At least two authors
      independently assessed each paper for inclusion and for study quality and
      extracted data. RESULTS: We included 13 randomised controlled trials with 896
      participants. Three of six trials that reported walking as an outcome found an
      improvement, as did four of the five trials reporting timed get up and go tests.
      Only one of the four trials that reported depression as an outcome found a
      positive effect. Both trials that reported quality of life found an improvement.
      CONCLUSIONS: There is some evidence that physical activity interventions improve
      physical function in older people with dementia. Evidence for an effect on
      depression and quality of life is limited.

PMID- 21905097
TI  - Personality changes in Alzheimer's disease: a systematic review.
AB  - OBJECTIVE: People with Alzheimer's disease (AD) commonly exhibit changes in
      personality that sometimes precede the other early clinical manifestations of the
      condition, such as cognitive impairment and mood changes. Although these
      personality changes reflect the impact of progressive brain damage, there are
      several possible patterns of personality change with dementia. Early
      identification of personality change might assist with the timely diagnosis of
      AD. The objective of this study was to review studies of personality change in
      AD. METHODS: Systematic searches of the PubMed, Ovid Medline, EBSCOhost,
      PsychINFO and CINAHL databases were undertaken from inception to November 2009.
      Published studies of informant-rated personality traits in AD patients were
      identified. Studies that mapped changes in traits from the five-factor model of
      personality which includes factors for Neuroticism, Extraversion, Openness,
      Agreeableness and Conscientiousness, were selected for analysis. The change in
      each of these five traits was calculated as the mean difference in score before
      and after the diagnosis of AD. RESULTS: There was a mean increase in Neuroticism
      of 10-20 T scores (equivalent to 1-2 SD), a decrease of the same magnitude in
      Extraversion, consistently reduced Openness and Agreeableness, and a marked
      decrease in Conscientiousness of about 20-30 T scores (equivalent to 2-3 SD).
      These changes were systematic and consistent. Particularly striking was the
      similarity of both the magnitude and direction of change in all studies reviewed.
      CONCLUSIONS: Conscientiousness and Neuroticism are the personality traits that
      exhibit the most change in dementia. These traits might be useful early markers
      of dementia.

PMID- 21905098
TI  - Demonstration of safety in Alzheimer's patients for intervention with an anti
      hypertensive drug Nilvadipine: results from a 6-week open label study.
AB  - BACKGROUND: Nilvadipine may lower rates of conversion from mild-cognitive
      impairment to Alzheimer's disease (AD), in hypertensive patients. However, it
      remains to be determined whether treatment with nilvadipine is safe in AD
      patients, given the higher incidence of orthostatic hypotension (OH) in this
      population, who may be more likely to suffer from symptoms associated with the
      further exaggeration of a drop in BP. OBJECTIVE: The aim of this study was to
      investigate the safety and tolerability of nilvadipine in AD patients. METHODS:
      AD patients in the intervention group (n = 56) received nilvadipine 8  mg daily
      over 6-weeks, compared to the control group (n = 30) who received no
      intervention. Differences in systolic (SBP) and diastolic (DBP) blood pressure,
      before and after intervention, was assessed using automated sphygmomanometer
      readings and ambulatory BP monitors (ABP), and change in OH using a finometer.
      Reporting of adverse events was monitored throughout the study. RESULTS: There
      was a significant reduction in the SBP of treated patients compared to non
      treated patients but no significant change in DBP. Individuals with higher
      initial blood pressure (BP) had greater reduction in BP but individuals with
      normal BP did not experience much change in their BP. While OH was present in 84%
      of the patients, there was no further drop in BP recorded on active stand
      studies. There were no significant differences in adverse event reporting between
      groups. CONCLUSION: Nilvadipine was well tolerated by patients with AD. This
      study supports further investigation of its efficacy as a potential treatment for
      AD.

PMID- 21905099
TI  - Depression in mild dementia: associations with diagnosis, APOE genotype and
      clinical features.
AB  - BACKGROUND: Depression is common in dementia, with important clinical
      implications. Few studies of depression in dementia with Lewy bodies are
      available, and the results are inconsistent. OBJECTIVE: To examine the frequency
      of depression and its characteristics and correlates, in people with mild
      dementia. METHODS: All referrals for patients with a first time diagnosis of
      dementia to geriatric and older psychiatry outpatient clinics in the counties of
      Rogaland and Hordaland in Western Norway from March 2005 to March 2007 were
      screened for the study. Participants and their caregivers underwent a
      comprehensive and standardised diagnostic and assessment procedure. The
      depression subitem of the neuropsychiatric inventory (NPId) and Montgomery and
      Asberg depression rating scale (MADRS) were used to estimate depression. Cut-off
      scores for any depression were 0/1 (NPId) and 6/7 (MADRS), and for clinically
      significant depression 3/4 and 14/15, respectively. RESULTS: Two hundered and
      twenty-three subjects with dementia participated, of whom 59 and 50% showed
      symptoms of depression assessed by NPI or MADRS, respectively, and 25 and 16% had
      clinically significant depression as measured by NPI and MADRS, respectively.
      Depression was more frequent in dementia with Lewy bodies (DLB) than in
      Alzheimer's disease (AD; p < 0.05). APOE genotype was available in 153 patients,
      and in AD, but not in DLB, a general linear model showed that the presence of
      APOEepsilon4 allele was significantly associated with depression (F = 4.14; p =
      0.045). CONCLUSION: Depression is common even in mild dementia, and more common
      and severe in DLB compared to AD. Future studies should explore the longitudinal
      course of depression in DLB, and the neural underpinnings of depression in DLB.

PMID- 21905100
TI  - The APOE polymorphism in Alzheimer's disease patients with neuropsychiatric
      symptoms and syndromes.
AB  - BACKGROUND: Neuropsychiatric symptoms (NPS) are a common feature of Alzheimer's
      disease (AD), resulting in particular AD endophenotypes. The common AD genetic
      risk factor apolipoprotein E (APOE) has been suggested underlying these AD
      endophenotypes. METHODS: APOE genotyping, a comprehensive geriatric assessment
      (CGA), and Neuropsychiatric Inventory were performed on 322 consecutive older
      patients. Patients were divided into three groups: AD with NPS (N = 93), AD
      without NPS (N = 108), and, as a control group, patients with no cognitive
      impairment (NoCI: N = 121). Patients with NPS were further sub-divided in four
      groups according to the European Alzheimer's Disease Consortium (EADC)
      classification of neuropsychiatric syndromes in AD: hyperactive, psychotic,
      affective, and apathetic. RESULTS: AD patients with NPS showed a significantly
      higher grade of cognitive impairment, more severity stage of dementia, more
      disability in the activities of daily living (ADL), and the instrumental ADL than
      AD patients without NPS. As expected, an higher frequency of APOE
      epsilon3/epsilon4 genotype was observed in patients with AD, both with and
      without NPS, than patients with NoCI. No difference in the distribution of APOE
      genotypes was found between AD patients with vs. without NPS. However, in AD
      patients APOE epsilon4-carriers, there was an increased risk of affective [odds
      ratio (OR): 2.34, 95% confidence interval (CI): 1.19-4.58) and apathetic (OR:
      2.24,95%CI: 1.19-4.22) syndromes. CONCLUSIONS: These findings did not suggest a
      significant association between APOE polymorphism and presence of NPS in AD
      patients. In AD patients with NPS, however, APOE epsilon4-carrier status was
      associated with an increased risk of affective and apathetic syndromes.

PMID- 21905101
TI  - Mental and psychological conditions, medical comorbidity and functional
      limitation: differential associations in older adults with cognitive impairment,
      depressive symptoms and co-existence of both.
AB  - OBJECTIVE: Cognitive impairment and depressive symptoms are common among the
      geriatric population but the co-occurrence of both is rarely studied. The purpose
      of this study was to identify and compare the factors associated with three
      groups of elderly people: those assessed with cognitive impairment alone (COG),
      depressive symptoms alone (DEP) or co-existence of both (COG-DEP). METHODS: The
      cross-sectional study included 600 community-dwellers ages 65 and older. All
      participants underwent a comprehensive evaluation. Global cognition was measured
      by the Mini-Mental State Examination (MMSE) and depressive symptoms were defined
      by the Geriatric Depression Scale (GDS). Specific chronic illnesses relevant to
      the Charlson comorbidity index (CCI) were self-reported. Functional status was
      evaluated by the Katz' basic (ADL) and Lawton's instrumental (IADL) activities of
      daily living scales. RESULTS: COG-DEP was explained by IADL dependence (OR: 11.9,
      95% CI: 4.59-30.78), ADL dependence (OR: 11.5, 95% CI: 5.59-23.69),
      cerebrovascular disease (OR: 3.6, 95% CI: 1.48-8.68), congestive heart failure
      (OR: 3.4, 95% CI: 1.77-6.59) and diabetes (OR: 2.6, 95% CI: 1.30-5.18), but it
      was best predicted by functional limitations in the adjusted model. Being
      functionally dependent and medically ill with shorter life expectancy was shown
      to significantly increase the odds of being DEP. Functional limitation in IADL
      was without distinction associated to COG, DEP and COG-DEP. CONCLUSION: The
      present results on COG, DEP and COG-DEP show the particular relevance of certain
      medical comorbidities and functional limitations to those three distinct groups
      of elderly people.

PMID- 21905102
TI  - Anxiety disorders, depressive episodes and cognitive impairment no dementia in
      community-dwelling older men and women.
AB  - BACKGROUND: Anxiety symptoms are highly prevalent in elders with mild cognitive
      disorders, but little is known about the associations of specific anxiety
      disorders to mild cognitive disorders. OBJECTIVE: To identify the clinical and
      subclinical anxiety disorders associated with cognitive impairment no dementia
      (CIND) and to determine whether these associations differ depending on sex and
      concomitant depressive episodes. METHOD: Participants constituted a random sample
      (n = 2414) of community-dwelling adults aged 65-96 years. The following clinical
      and subclinical DSM-IV anxiety disorders were identified with a semi-structured
      interview: specific phobia, social phobia, agoraphobia, panic disorder, obsessive
      compulsive, and generalized anxiety disorder (GAD). Major depressive episodes or
      minor depression (MDE/MD) were also determined based on the DSM-IV criteria. CIND
      cases were defined based on Mini-Mental State Examination (MMSE) cut-offs (15th
      percentile) stratified for age, education, and sex. Potentially confounding
      variables (age, education, MDE/MD, chronic diseases, and psychotropic drug use)
      were statistically controlled. RESULTS: In men, after adjusting for confounding
      variables, CIND was associated with subclinical GAD (odds ratio (OR): 4.93, 95%
      confidence interval: 1.84-13.23). Further analyses showed that in men, CIND was
      related to clinical/subclinical GAD whether MDE/MD was present (7.05, 1.88-26.43)
      or absent (9.33, 3.24-26.83). In women, CIND was not linked to any clinical or
      subclinical anxiety disorder. CONCLUSIONS: These results suggest that in
      community-dwelling elders, GAD is the main anxiety disorder associated with poor
      global cognitive functioning. Moreover, this association is modified by sex, but
      not by the presence of depressive episodes.

PMID- 21905103
TI  - Fibrinogen and cognitive function in very old non-demented men.

PMID- 21905104
TI  - Survival of patients with incident dementia who had a pre-existing psychiatric
      disorder: a population-based 7-year follow-up study.
AB  - OBJECTIVES: Although it is widely accepted that psychiatric disorders and
      dementia coexist and survival data for dementia patients have been published,
      there is a paucity of information regarding the survival of patients with a
      psychiatric disorder who develop dementia. This study fills this information gap
      providing survival data on patients with such comorbidity and identifies
      mortality risk factors. METHODS: All residents of Saskatchewan, a Canadian
      province, diagnosed with psychiatric problems and/or dispensed a psychiatric drug
      in 2000 and without dementia were followed through to 31 December 2006; the
      development of incident dementia was noted. Median survival time (in months) and
      selected predictors of mortality were measured. Analyses used Cox's proportional
      hazard model. Incidence density of dementia for the year 2000 was also computed.
      RESULTS: By December 2006, 5,583 subjects with psychiatric disorders in 2000 had
      been diagnosed with incident dementia, and 60.65% of them died. Dementia
      incidence density in this population for 2000 was 0.01 per 1000 person years at
      risk among those aged 18-64 years and rapidly increased to 3.13 per 1000 person
      years at risk among those aged 75 to 84 years. The median survival time from
      dementia onset to death was 32.66 months (interquartile range 31.21-34.14). Being
      male, later age of onset of dementia, having a lower income, and a high chronic
      disease score predicted shorter survival. CONCLUSIONS: The comorbidity of
      psychiatric disorders and dementia resulted in shorter survival compared with
      that reported for patients with dementia only. These findings can be used for
      prognosis for patients, caregivers, and service providers.

PMID- 21905105
TI  - Structural analysis of CPF_2247, a novel alpha-amylase from Clostridium
      perfringens.
AB  - CPF_2247 from Clostridium perfringens ATCC 13124 was identified as a putative
      carbohydrate-active enzyme by its low sequence identity to endo-beta-1,4
      glucanases belonging to family 8 of the glycoside hydrolase classification. The X
      ray crystal structure of CPF_2247 determined to 2.0 A resolution by single
      wavelength anomalous dispersion using seleno-methionine-substituted protein
      revealed an (alpha/alpha)(6) barrel fold. A large cleft on the surface of the
      protein contains residues that are structurally conserved with key elements of
      the catalytic machinery in clan GH-M glycoside hydrolases. Assessment of CPF_2247
      as a carbohydrate-active enzyme disclosed alpha-glucanase activity on amylose,
      glycogen, and malto-oligosaccharides.

PMID- 21905106
TI  - Predicting large-scale conformational changes in proteins using energy-weighted
      normal modes.
AB  - We report the development of a method to improve the sampling of protein
      conformational space in molecular simulations. It is shown that a principal
      component analysis of energy-weighted normal modes in Cartesian coordinates can
      be used to extract vectors suitable for describing the dynamics of protein
      substructures. The method can operate with either atomistic or user-defined
      coarse-grained models of protein structure. An implicit reverse coarse-graining
      allows the dynamics of all-atoms to be recovered when a coarse-grained model is
      used. For an external test set of four proteins, it is shown that the new method
      is more successful than normal mode analysis in describing the large-scale
      conformational changes observed on ligand binding. The method has potential
      applications in protein-ligand and protein-protein docking and in biasing
      molecular dynamics simulations.

PMID- 21905107
TI  - The VSGB 2.0 model: a next generation energy model for high resolution protein
      structure modeling.
AB  - A novel energy model (VSGB 2.0) for high resolution protein structure modeling is
      described, which features an optimized implicit solvent model as well as physics
      based corrections for hydrogen bonding, pi-pi interactions, self-contact
      interactions, and hydrophobic interactions. Parameters of the VSGB 2.0 model were
      fit to a crystallographic database of 2239 single side chain and 100 11-13
      residue loop predictions. Combined with an advanced method of sampling and a
      robust algorithm for protonation state assignment, the VSGB 2.0 model was
      validated by predicting 115 super long loops up to 20 residues. Despite the
      dramatically increasing difficulty in reconstructing longer loops, a high
      accuracy was achieved: all of the lowest energy conformations have global
      backbone RMSDs better than 2.0 A from the native conformations. Average global
      backbone RMSDs of the predictions are 0.51, 0.63, 0.70, 0.62, 0.80, 1.41, and
      1.59 A for 14, 15, 16, 17, 18, 19, and 20 residue loop predictions, respectively.
      When these results are corrected for possible statistical bias as explained in
      the text, the average global backbone RMSDs are 0.61, 0.71, 0.86, 0.62, 1.06,
      1.67, and 1.59 A. Given the precision and robustness of the calculations, we
      believe that the VSGB 2.0 model is suitable to tackle "real" problems, such as
      biological function modeling and structure-based drug discovery.

PMID- 21905108
TI  - Ionic strength dependence of F-actin and glycolytic enzyme associations: a
      Brownian dynamics simulations approach.
AB  - The association of glycolytic enzymes with F-actin is proposed to be one
      mechanism by which these enzymes are compartmentalized, and, as a result, may
      possibly play important roles for: regulation of the glycolytic pathway,
      potential substrate channeling, and increasing glycolytic flux. Historically, in
      vitro experiments have shown that many enzyme/actin interactions are dependent on
      ionic strength. Herein, Brownian dynamics (BD) examines how ionic strength
      impacts the energetics of the association of F-actin with the glycolytic enzymes:
      lactate dehydrogenase (LDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH),
      fructose-1,6-bisphosphate aldolase (aldolase), and triose phosphate isomerase
      (TPI). The BD simulations are steered by electrostatics calculated by Poisson
      Boltzmann theory. The BD results confirm experimental observations that the
      degree of association diminishes as ionic strength increases but also suggest
      that these interactions are significant, at physiological ionic strengths.
      Furthermore, BD agrees with experiments that muscle LDH, aldolase, and GAPDH
      interact significantly with F-actin whereas TPI does not. BD indicates
      similarities in binding regions for aldolase and LDH among the different species
      investigated. Furthermore, the residues responsible for salt bridge formation in
      stable complexes persist as ionic strength increases. This suggests the
      importance of the residues determined for these binary complexes and specificity
      of the interactions. That these interactions are conserved across species, and
      there appears to be a general trend among the enzymes, support the importance of
      these enzyme-F-actin interactions in creating initial complexes critical for
      compartmentation.

PMID- 21905109
TI  - PackHelix: a tool for helix-sheet packing during protein structure prediction.
AB  - The three-dimensional structure of a protein is organized around the packing of
      its secondary structure elements. Predicting the topology and constructing the
      geometry of structural motifs involving alpha-helices and/or beta-strands are
      therefore key steps for accurate prediction of protein structure. While many
      efforts have focused on how to pack helices and on how to sample exhaustively the
      topologies and geometries of multiple strands forming a beta-sheet in a protein,
      there has been little progress on generating native-like packings of helices on
      sheets. We describe a method that can generate the packing of multiple helices on
      a given beta-sheet for alphabetaalpha sandwich type protein folds. This method
      mines the results of a statistical analysis of the conformations of alphabeta(2)
      motifs in protein structures to provide input values for the geometric attributes
      of the packing of a helix on a sheet. It then proceeds with a geometric builder
      that generates multiple arrangements of the helices on the sheet of interest by
      sampling through these values and performing consistency checks that guarantee
      proper loop geometry between the helices and the strands, minimal number of
      collisions between the helices, and proper formation of a hydrophobic core. The
      method is implemented as a module of ProteinShop. Our results show that it
      produces structures that are within 4-6 A RMSD of the native one, regardless of
      the number of helices that need to be packed, though this number may increase if
      the protein has several helices between two consecutive strands in the sequence
      that pack on the sheet formed by these two strands.

PMID- 21905110
TI  - Computed structures of point deletion mutants and their enzymatic activities.
AB  - Point deletions in enzymes can vary in effect from negligible to complete loss of
      activity; however, these effects are not generally predictable. Deletions are
      widely observed in nature and often result in diseases such as cancer, cystic
      fibrosis, or osteogenesis imperfecta. Here, we have developed an algorithm to
      model the perturbed structures of deletion mutants with the ultimate goal of
      predicting their activities. The algorithm works by deleting the specified
      residue from the wild-type structure, creating a gap that is closed using a
      combination of local and global moves that change the backbone torsion angles of
      the protein structure. On a set of five proteins for which both wild-type and
      deletion mutant x-ray crystal structures are available, the algorithm produces
      deep, narrow energy funnels within 1.5 A of the crystal structure for the
      deletion mutants. To assess the ability of our algorithm to predict activity from
      the predicted structures, we tested the correlation of experimental activity with
      several measures of the predicted structure ensemble using a set of 45 point
      deletions from ricin. Estimates incorporating likely prevalence of active and
      inactive deletion sites suggest that activity can be predicted correctly over 60%
      of the time from the active site root-mean squared deviation of the lowest energy
      predicted structures. The predictions are stronger than simple sequence
      organization measures, but more fundamental work is required in structure
      prediction and enzyme activity determination to allow consistent prediction of
      activity.

PMID- 21905111
TI  - A survey of hemoglobin quaternary structures.
AB  - We perform an analysis of the quaternary structure and dimer/dimer interface in
      the crystal structures of 165 human hemoglobin tetramers; 112 are in the T, 17
      the R, 14 the Y (or R2) state; 11 are high-affinity T state mutants, and 11 may
      either be intermediates between the states, or off the allosteric transition
      pathway. The tertiary structure is fixed within each state, in spite of the
      different ligands, mutations, and chemical modifications present in individual
      entries. The geometry of the tetramer assembly is essentially the same in all the
      R or the Y state entries; it is slightly different in high salt and low salt
      crystals of T state hemoglobins. The dimer/dimer interface differs in terms of
      size, chemical composition and polar interactions, between the states. It is
      loosely packed, like crystal packing contacts or the subunit interface of weakly
      associated homodimers, and unlike most oligomeric proteins, which have close
      packed interfaces. The loose packing is most obvious in the liganded forms, where
      the tetramer is known to dissociate at low concentration. We identify cavities
      that contribute to the loose packing of the alpha1beta2 and alpha2beta1 contacts.
      Two pairs of cavities occur recurrently in both the T and the R state tetramers.
      They may contribute to the allosteric mechanism by facilitating the subunit
      movements and the tertiary structure changes that accompany the transition from T
      to R to Y.

PMID- 21905112
TI  - Three ways in, one way out: water dynamics in the trans-membrane domains of the
      inner membrane translocase AcrB.
AB  - Powered by proton-motive force, the inner membrane translocase AcrB is the engine
      of the AcrAB-TolC efflux pump in Escherichia coli. As proton conduction in
      proteins occurs along hydrogen-bonded networks of polar residues and water
      molecules, knowledge of the protein-internal water distribution and water
      interacting residues allows drawing conclusions to possible pathways of proton
      conduction. Here, we report a series of 6* 50 ns independent molecular dynamics
      simulations of asymmetric AcrB embedded in a phospholipid/water environment.
      Simulating each monomer in its proposed protonation state, we calculated for each
      trans-membrane domain the average water distribution, identified residues
      interacting with these waters and quantified each residue's frequency of water
      hydrogen bond contact. Combining this information we find three possible routes
      of proton transfer connecting a continuously hydrated region of known key
      residues in the TMD interior to bulk water by one cytoplasmic and up to three
      periplasm water channels in monomer B and A. We find that water access of the
      trans-membrane domains is regulated by four groups of residues in a combination
      of side chain re-orientations and shifts of trans-membrane helices. Our findings
      support a proton release event via Arg971 during the C intermediate or in the
      transition to A, and proton uptake occurring in the A or B state or during a so
      far unknown intermediate in between B and C where cytoplasmic water access is
      still possible. Our simulations suggest experimentally testable hypotheses, which
      have not been investigated so far.

PMID- 21905113
TI  - The active-inactive transition of human thymidylate synthase: targeted molecular
      dynamics simulations.
AB  - Human thymidylate synthase (hTS) is an established anticancer target. It
      catalyses the production of 2'-deoxythymidine-5'-monophosphate, an essential
      building block for DNA synthesis. Because of the development of cellular drug
      resistance against current hTS inhibitors, alternative inhibition strategies are
      needed. hTS exists in two forms, active and inactive, defined by the conformation
      of the active-site (AS) loop, which carries the catalytic cysteine, C195. To
      investigate the mechanism of activation and inactivation, targeted molecular
      dynamics (TMD) simulations of the transitions between active and inactive states
      of hTS were performed. Analysis of changes in the dihedral angles in the AS loop
      during different TMD simulations revealed complex conformational transitions.
      Despite hTS being a homodimeric enzyme and the conformational transition
      significantly involving the dimer interface, the transition occurs in an
      asymmetric, sequential manner via an ensemble of pathways. In addition to C195,
      which reoriented during the simulations, other key residues in the rotation of
      the AS loop included W182 and R185. The interactions of the cognate bulky W182
      residues at the dimer interface hindered the simultaneous twist of the AS loops
      in the hTS dimer. Interactions of R185, which is unique for hTS, with ligands at
      different allosteric sites affected the activation transition. In addition to
      providing insights into the activation/inactivation mechanism of hTS and how
      conformational transitions can occur in homodimeric proteins, our observations
      suggest that blocking of AS loop rotation by ligands binding in the large cavity
      between the loops could be one way to stabilize inactive hTS and inhibit the
      enzyme.

PMID- 21905115
TI  - Progress in super long loop prediction.
AB  - Sampling errors are very common in super long loop (referring here to loops that
      have more than thirteen residues) prediction, simply because the sampling space
      is vast. We have developed a dipeptide segment sampling algorithm to solve this
      problem. As a first step in evaluating the performance of this algorithm, it was
      applied to the problem of reconstructing loops in native protein structures. With
      a newly constructed test set of 89 loops ranging from 14 to 17 residues, this
      method obtains average/median global backbone root-mean-square deviations (RMSDs)
      to the native structure (superimposing the body of the protein, not the loop
      itself) of 1.46/0.68 A. Specifically, results for loops of various lengths are
      1.19/0.67 A for 36 fourteen-residue loops, 1.55/0.75 A for 30 fifteen-residue
      loops, 1.43/0.80 A for 14 sixteen-residue loops, and 2.30/1.92 A for nine
      seventeen-residue loops. In the vast majority of cases, the method locates energy
      minima that are lower than or equal to that of the minimized native loop, thus
      indicating that the new sampling method is successful and rarely limits
      prediction accuracy. Median RMSDs are substantially lower than the averages
      because of a small number of outliers. The causes of these failures are examined
      in some detail, and some can be attributed to flaws in the energy function, such
      as pi-pi interactions are not accurately accounted for by the OPLS-AA force field
      we employed in this study. By introducing a new energy model which has a superior
      description of pi-pi interactions, significantly better results were achieved for
      quite a few former outliers. Crystal packing is explicitly included in order to
      provide a fair comparison with crystal structures.

PMID- 21905116
TI  - Elastic network model-based normal mode analysis reveals the conformational
      couplings in the tripartite AcrAB-TolC multidrug efflux complex.
AB  - The AcrAB-TolC drug efflux system, energized by proton movement down the
      transmembrane electrochemical gradient, is responsible for the resistance of the
      organism to a wide range of drugs. Experimental data suggest functional roles of
      each part of the assembly, but the detailed working mechanism of this machinery
      remains elusive. We used elastic network-based normal mode analysis (NMA) to
      explore the conformational dynamics of the AcrAB-TolC complex. The intrinsic
      flexibilities of the pore domain in AcrB monomer conform to the previously
      proposed three-step functionally rotating mechanism for asymmetric AcrB trimer.
      Conformational couplings across monomers in the AcrB trimer were observed, and
      the coupling between the transmembrane domain and the other parts of AcrB are
      strengthened through trimeric assembly. In the tripartite AcrAB-TolC assembly
      obtained through molecular docking, concerted motions were observed not only at
      the direct contact interfaces between various components but also between distant
      parts of the whole complex. The presence of AcrA was shown to significantly
      strengthen the motional couplings between AcrB and TolC. Overall, NMA revealed an
      allosteric network in the AcAB-TolC efflux system, which provides hints to our
      understanding of its detailed working mechanism.

PMID- 21905114
TI  - Prechemistry versus preorganization in DNA replication fidelity.
AB  - The molecular origin of nucleotide insertion catalysis and fidelity of DNA
      polymerases is explored by means of computational simulations. Special attention
      is paid to the examination of the validity of proposals that invoke prechemistry
      effects, checkpoints concepts, and dynamical effects. The simulations reproduce
      the observed fidelity in Pol beta, starting with the relevant observed X-ray
      structures of the complex with the right (R) and wrong (W) nucleotides. The
      generation of free energy surfaces for the R and W systems also allowed us to
      analyze different proposals about the origin of the fidelity and to reach several
      important conclusions. It is found that the potential of mean force (PMF)
      obtained by proper sampling does not support QM/MM-based proposals of a large
      barrier before the prechemistry state. Furthermore, examination of dynamical
      proposals by the renormalization approach indicates that the motions from open to
      close configurations do not contribute to catalysis or fidelity. Finally we
      discuss and analyze the induced fit concept and show that, despite its
      importance, it does not explain fidelity. That is, the fidelity is apparently due
      to the change in the preorganization of the chemical site, as a result of the
      relaxation of the binding site upon binding of the incorrect nucleotide. Finally
      and importantly, since the issue is the barrier associated with the enzyme
      substrate (ES)/DNA complex at the chemical transition state and not the path to
      this complex formation (unless this path involves rate determining steps), it is
      also not useful to invoke checkpoints while discussing fidelity.

PMID- 21905118
TI  - Inhibition of alpha-synuclein aggregation by small heat shock proteins.
AB  - The fibrillization of alpha-synuclein (alpha-syn) is a key event in the
      pathogenesis of alpha-synucleinopathies. Mutant alpha-syn (A53T, A30P, or E46K),
      each linked to familial Parkinson's disease, has altered aggregation properties,
      fibril morphologies, and fibrillization kinetics. Besides alpha-syn, Lewy bodies
      also contain several associated proteins including small heat shock proteins
      (sHsps). Since alpha-syn accumulates intracellularly, molecular chaperones like
      sHsps may regulate alpha-syn folding and aggregation. Therefore, we investigated
      if the sHsps alphaB-crystallin, Hsp27, Hsp20, HspB8, and HspB2B3 bind to alpha
      syn and affect alpha-syn aggregation. We demonstrate that all sHsps bind to the
      various alpha-syns, although the binding kinetics suggests a weak and transient
      interaction only. Despite this transient interaction, the various sHsps inhibited
      mature alpha-syn fibril formation as shown by a Thioflavin T assay and atomic
      force microscopy. Interestingly, HspB8 was the most potent sHsp in inhibiting
      mature fibril formation of both wild-type and mutant alpha-syn. In conclusion,
      sHsps may regulate alpha-syn aggregation and, therefore, optimization of the
      interaction between sHsps and alpha-syn may be an interesting target for
      therapeutic intervention in the pathogenesis of alpha-synucleinopathies.

PMID- 21905117
TI  - Mycobacterium tuberculosis Rv0899 defines a family of membrane proteins
      widespread in nitrogen-fixing bacteria.
AB  - The Mycobacterium tuberculosis membrane protein Rv0899 confers adaptation of the
      bacterium to acidic environments. Due to strong sequence homology of its C
      terminus to bacterial OmpA-like domains, Rv0899 has been proposed to constitute
      an outer membrane porin of M. tuberculosis. However, OmpA-like domains are
      widespread in a wide variety of bacterial proteins with different functions.
      Furthermore, the three-dimensional structure of Rv0899 does not contain a
      transmembrane beta-barrel, and recent evidence demonstrates that it does not have
      porin activity. Instead, the rv0899 gene is part of an operon (rv0899-rv0901)
      that is required for fast ammonia secretion, pH neutralization, and growth of M.
      tuberculosis in acidic environments. The mechanism whereby these functions are
      accomplished is not known. To gain further functional insights, a targeted search
      of the genomic databases was performed for proteins with sequence similarity
      beyond the OmpA-like C-terminus. The results presented here, show that Rv0899
      like proteins are widespread in bacteria with functions in nitrogen metabolism,
      adaptation to nutrient poor environments, and/or establishing symbiosis with the
      host organism, and appear to form a protein family. These findings suggest that
      M. tuberculosis Rv0899 may also assist similar processes and lend further support
      to its role in ammonia secretion and M. tuberculosis adaptation to the host
      environment.

PMID- 21905119
TI  - Molecular dynamics modeling of tubulin C-terminal tail interactions with the
      microtubule surface.
AB  - Tubulin, an alpha/beta heterodimer, has had most of its 3D structure analyzed;
      however, the carboxy (C)-termini remain elusive. Importantly, the C-termini play
      critical roles in regulating microtubule structure and function. They are sites
      of most of the post-translational modifications of tubulin and interaction sites
      with molecular motors and microtubule-associated proteins. Simulated annealing
      was used in our molecular dynamics modeling to predict the interactions of the C
      terminal tails with the tubulin dimer. We examined differences in their
      flexibility, interactions with the body of tubulin, and the existence of
      structural motifs. We found that the alpha-tubulin tail interacts with the H11
      helix of beta-tubulin, and the beta-tubulin tail interacts with the H11 helix of
      alpha-tubulin. Tail domains and H10/B9 loops interact with each other and compete
      for interactions with positively-charged residues of the H11 helix on the
      neighboring monomer. In a simulation in which alpha-tubulin's H10/B9 loop
      switches on sub-nanosecond intervals between interactions with the C-terminal
      tail of alpha-tubulin and the H11 helix of beta-tubulin, the intermediate domain
      of alpha-tubulin showed more fluctuations compared to those in the other
      simulations, indicating that tail domains may cause shifts in the position of
      this domain. This suggests that C-termini may affect the conformation of the
      tubulin dimer which may explain their essential function in microtubule formation
      and effects on ligand binding to microtubules. Our modeling also provides
      evidence for a disordered-helical/helical double-state system of the T3/H3 region
      of the microtubule, which could be linked to depolymerization following GTP
      hydrolysis.

PMID- 21905120
TI  - Crystal structure of Mycobacterium tuberculosis Rv3168: a putative aminoglycoside
      antibiotics resistance enzyme.

PMID- 21905121
TI  - Solution NMR structure of VF0530 from Vibrio fischeri reveals a nucleic acid
      binding function.
AB  - Protein domain family PF09905 (DUF2132) is a family of small domains of unknown
      function that are conserved in a wide range of bacteria. Here we describe the
      solution NMR structure of the 80-residue VF0530 protein from Vibrio fischeri, the
      first structural representative from this protein domain family. We demonstrate
      that the structure of VF0530 adopts a unique four-helix motif that shows some
      similarity to the C-terminal double-stranded DNA (dsDNA) binding domain of RecA,
      as well as other nucleic acid binding domains. Moreover, gel shift binding data
      indicate a potential dsDNA binding role for VF0530.

PMID- 21905122
TI  - Ab initio phasing of a nucleoside hydrolase-related hypothetical protein from
      Saccharophagus degradans that is associated with carbohydrate metabolism.

PMID- 21905123
TI  - Structural evidence that puromycin hydrolase is a new type of aminopeptidase with
      a prolyl oligopeptidase family fold.

PMID- 21905125
TI  - Cortical spreading depression in alpha-synuclein knockout mice.

PMID- 21905124
TI  - Pre- and postsynaptic effects of norepinephrine on gamma-aminobutyric acid
      mediated synaptic transmission in layer 2/3 of the rat auditory cortex.
AB  - Noradrenergic terminals from the locus coeruleus release norepinephrine (NE)
      throughout most brain areas, including the auditory cortex, where they affect
      neural processing by modulating numerous cellular properties including the
      inhibitory gamma-aminobutyric acid (GABA)ergic transmission. We recently
      demonstrated that NE affects GABAergic signaling onto cortical pyramidal cells in
      a complex manner. In this study, we used a combination of patch-clamp recording
      and immunohistochemical techniques to identify the synaptic site and the location
      of the adrenergic receptors involved in the modulation of GABAergic signaling in
      cortical layer 2/3 of the rat. Our results showed that NE increases the frequency
      of spike-independent miniature inhibitory postsynaptic currents (mIPSCs), as well
      as the probability of release of unitary inhibitory postsynaptic currents (IPSCs)
      obtained with patch-clamp pair-recordings. The pharmacology of mIPSCs and the
      identification of adrenergic receptors in neurons containing the GABAergic marker
      parvalbumin (PV) suggest that NE increases the presynaptic probability of GABA
      release by activating alpha(2) - and beta-receptors on PV-positive neurons. On
      the contrary, bath-applied NE or phenylephrine, decreased the current mediated by
      pressure application of the GABA(A) -receptor agonist muscimol, as well as the
      amplitude-but not the frequency-of mIPSCs, indicating that activation of
      postsynaptic alpha(1) adrenoceptors reversibly depressed GABAergic currents. We
      speculate that while a generalized postsynaptic decrease of GABAergic inhibition
      might decrease the synaptic activation threshold for pyramidal neurons
      corresponding to an alert state, NE might promote perception and sensory binding
      by facilitating lateral inhibition as well as the production of gamma
      oscillations by a selective enhancement of perisomatic inhibition.

PMID- 21905126
TI  - Striatal mitochondria in subjects with chronic undifferentiated vs. chronic
      paranoid schizophrenia.
AB  - Schizophrenia (SZ) is a heterogeneous disease with a spectrum of symptoms, risk
      factors, and etiology. Abnormalities in mitochondria, the energy-producing
      organelles of the cell, have been observed in mixed cohorts of subjects with SZ.
      The purpose of the present study was to determine if striatal mitochondria were
      differentially affected in two different DSM-IV subgroups of SZ. Postmortem
      striatal tissue was examined from normal controls (NC), chronic paranoid SZs
      (SZP), and chronic undifferentiated SZs (SZU). Tissue was processed for calbindin
      immunohistochemistry to identify striosomal compartments, prepared for electron
      microscopy and analyzed using stereological methods. In both caudate and putamen,
      the density of mitochondria in the neuropil was decreased in SZP compared to both
      NCs and SZU. In the putamen, both the SZP and the SZU subgroups had fewer
      mitochondria per synapse than did NCs. When examining patch matrix compartments,
      striatal compartments associated with different circuitry and function, only the
      matrix exhibited changes. In the caudate matrix, the SZP subgroup had fewer
      mitochondria in the neuropil than did the SZU and NCs. In the putamen matrix, the
      SZP had fewer mitochondria in the neuropil as compared to NCs, but not the SZU.
      The numbers of mitochondria per synapse in both the SZP and the SZU groups were
      similar to each other and fewer than that of NCs. A decrease in mitochondrial
      density in the neuropil distinguishes the SZP from the SZU subgroup, which could
      be associated with the symptoms of paranoia and/or could represent a protective
      mechanism against some of the symptoms that are less pronounced in this subtype
      than in the SZU subgroup such as cognitive and emotional deficits.

PMID- 21905127
TI  - Subdiaphragmatic vagotomy increases the sensitivity of lumbar Adelta primary
      afferent neurons along with voltage-dependent potassium channels in rats.
AB  - Subdiaphragmatic vagal dysfunction causes chronic pain. To verify whether this
      chronic pain is accompanied by enhanced peripheral nociceptive sensitivity, we
      evaluated primary afferent neuronal excitability in subdiaphragmatic vagotomized
      (SDV) rats. SDV rats showed a decrease in the electrical stimuli-induced hind
      limb-flexion threshold at 250 Hz, but showed no similar effect at 5 or 2000 Hz,
      which indicated that lumbar primary afferent Adelta sensitivity was enhanced in
      SDV rats. The whole-cell patch-clamp technique also revealed the hyper
      excitability of acutely dissociated medium-sized lumbar dorsal root ganglion
      (DRG) neurons isolated from SDV rats. The contribution of changes in voltage
      dependent potassium (Kv) channels was assessed, and transient A-type K(+) (I(A) )
      current density was apparently decreased. Moreover, Kv4.3 immunoreactivity in
      medium-sized DRG neurons was significantly reduced in SDV rats compared to sham.
      These results indicate that SDV causes hyper-excitability of lumbar primary
      Adelta afferent neurons, which may be induced along with suppressing I(A)
      currents via the decreased expression of Kv4.3. Thus, peripheral Adelta
      neuroplasticity may contribute to the chronic lower limb pain caused by SDV.

PMID- 21905128
TI  - The acute administration of the selective dopamine D(3)  receptor antagonist SB
      277011A reverses conditioned place aversion produced by naloxone precipitated
      withdrawal from acute morphine administration in rats.
AB  - We examined the effect of SB-277011A, a selective D(3) receptor antagonist, on
      the conditioned place aversion (CPA) response associated with naloxone-induced
      withdrawal from acute morphine administration in male Sprague-Dawley rats.
      Morphine (5.6 mg/kg i.p.) was given, followed 4 hrs later by naloxone (0.3 mg/kg
      i.p.) and prior to placing the animals in one specific chamber of the test
      apparatus. All animals were subjected to 2 of these trials. A significant CPA
      occurred in animals that received an i.p. injection of vehicle 30 minutes prior
      to the measurement of chamber preference. The pretreatment of animals (30 minutes
      prior to testing) with 3 mg/kg i.p. of SB-277011A did not significantly alter the
      CPA compared to animals treated with vehicle (1 ml/kg i.p. of deionized distilled
      water). In contrast, the acute pretreatment of animals with 6, 12 or 24 mg/kg
      i.p. of SB-277011A significantly decreased the CPA compared to vehicle-treated
      animals. In fact, the 12 and 24 mg/kg doses of SB-277011A significantly increased
      the time spent in the chamber where animals were paired with morphine and
      naloxone. These results suggest that the selective antagonism of D(3) receptors
      attenuates the CPA produced by a model of naloxone-induced withdrawal from acute
      morphine dependence.

PMID- 21905129
TI  - Insights into the Sigma-1 receptor chaperone's cellular functions: a microarray
      report.
AB  - We previously demonstrated that Sig-1Rs are critical regulators in neuronal
      morphogenesis and development via the regulation of oxidative stress and
      mitochondrial functions. In the present study, we sought to identify pathways and
      genes that are affected by Sig-1R. Gene expression profiles were examined in rat
      hippocampal neurons that had been cultured for 18 days in vitro (DIV). The cells
      were transduced with AAV siRNA targeting Sig-1R on DIV 10 for 7 days, followed by
      gene expression analysis using a rat genome cDNA array. The gene array results
      indicated that Sig-1R knockdown hampered cellular functions including steroid
      biogenesis, protein ubiquitination, actin cytoskeleton network, and Nrf-2
      mediated oxidative stress. Many of the cellular components important for actin
      polymerization and synapse plasticity, including F-actin capping protein and
      neurofilaments, were significantly changed in AAV-siSig-1R neurons. Further,
      cytochrome c was reduced in AAV-Sig-1R neurons whereas free-radical generating
      enzymes including cytochrome p450 and cytochrome b-245 were increased. The
      microarray results also suggest that Sig-1Rs may regulate genes that are involved
      in the pathogenesis of many CNS diseases including Alzheimer's disease and
      Parkinson's disease. These data further confirmed that Sig-1Rs play critical
      roles in the CNS and thus these findings may aid in future development of
      therapeutic treatments targeting neurodegenerative disorders.

PMID- 21905130
TI  - A new and general fabrication of an aligned carbon nanotube/polymer film for
      electrode applications.

PMID- 21905131
TI  - Simultaneous enhancement of open-circuit voltage, short-circuit current density,
      and fill factor in polymer solar cells.

PMID- 21905132
TI  - From 2D to 3D: a single-crystal-to-single-crystal photochemical framework
      transformation and phenylmethanol oxidation catalytic activity.

PMID- 21905133
TI  - Left or right? The direction of compression-generated vortex-like flow selects
      the macroscopic chirality of interfacial molecular assemblies.
AB  - A new method is described through which the macroscopic chirality of interfacial
      molecular assemblies of an achiral porphyrin can be mechanically controlled using
      an original yet efficient Langmuir-Blodgett (LB) technique. By using the
      unilateral compression geometry, we find that the assemblies deposited from the
      mirror regions of the LB trough display mirror macroscopic chirality. It is
      indicated that vortex-like flows could be generated during compression, and that
      it is the direction of this compression-generated vortex-like flow that determine
      the macroscopic chirality of the formed assemblies. Moreover, the standard sample
      fabrication method with bilateral compression geometry is reformed, and we find
      that the samples formulated around the left-hand- and right-hand-side Langmuir
      barriers display opposite macroscopic chiralities. The results suggest that
      mechanically controlled supramolecular chirogenesis could be efficiently realized
      through such an LB technique. The investigation establishes a new forum for
      further investigation of the mechanically induced preferred supramolecular
      chirality in terms of interfacial organization, and provides the old LB technique
      with new opportunities for controlling the macroscopic chirality of a
      supramolecular system that is wholly composed of achiral units.

PMID- 21905134
TI  - A trinuclear copper(II) cryptate and its MU3-CO3 cascade complex: thermodynamics,
      structural and magnetic properties.
AB  - The 2,4,6-triethylbenzene-capped hexaamine macrobicycle with pyridyl spacers
      (pyr) was able to coordinate three copper(II) ions within its cavity.
      Potentiometric studies performed at 298.2 K in MeOH/H(2)O (50:50 v/v) and at
      ionic strength 0.10 mol dm(-3) in KNO(3) revealed that trinuclear species
      predominate in solution from pH 5.0, the hydroxo complexes being the main
      species, which start forming at unusual very low pH values. The single-crystal X
      ray determination of the trinuclear complex showed that the three copper centres
      have square-planar geometry, arranged in an almost equilateral triangle, and have
      carbonate bridging the three metal centres. The presence of carbonate resulted
      from fixation of atmospheric CO(2). The present study represents the first MU(3)
      CO(3)-bridged trinuclear copper(II) complex located in the interior of a
      macrobicyclic cavity. The magnetic data of [Cu(3)(pyr)(MU(3)-CO(3))].(ClO(4))(4)
      showed ferromagnetic intramolecular interactions [J=3.80 cm(-1), based on the
      Hamiltonian H=-J(S(1)S(2)+S(2)S(3)+S(1)S(3))] yielding a spin quartet, S=3/2,
      ground state. Density functional calculations on the experimental geometry of the
      trinuclear complex showed that the ferromagnetic nature of the magnetic coupling
      can be attributed to the syn-anti conformation of the carbonato bridge, and a
      magneto-structural correlation, based on the different conformations (syn-anti,
      syn-syn and anti-anti), is presented. The interesting properties observed, namely
      the lowering of the pK(a) of coordinated water molecules to unusual values and
      the good fit of the carbonate anion between the copper centres, derive from the
      special architecture of pyr.

PMID- 21905135
TI  - Biomimetic oxidation reactions of a naked manganese(V)-oxo porphyrin complex.
AB  - The intrinsic reactivity of a manganese(V)-oxo porphyrin complex, a typically
      fleeting intermediate in catalytic oxidation reactions in solution, has been
      elucidated in a study focused on its gas-phase ion-chemistry. The naked high
      valent Mn(V)-oxo porphyrin intermediate 1 ([(tpfpp)Mn(V)O](+); tpfpp=meso
      tetrakis(pentafluorophenyl)porphinato dianion), has been obtained by controlled
      treatment of [(tpfpp)Mn(III)]Cl (2-Cl) with iodosylbenzene in methanol, delivered
      in the gas phase by electrospray ionization and assayed by FT-ICR mass
      spectrometry. A direct kinetic study of the reaction with selected substrates,
      each containing a heteroatom X (X=S, N, P) including amines, sulfides, and
      phosphites, was thus performed. Ionic products arising from electron transfer
      (ET), hydride transfer (HT), oxygen-atom transfer (OAT), and formal addition
      (Add) may be observed, with a predominance of two-electron processes, whereas the
      product of hydrogen-atom transfer (HAT), [(tpfpp)Mn(IV)OH](+), is never detected.
      A thermochemical threshold for the formation of the product radical cation allows
      an evaluation of the electron-transfer ability of a Mn(V)-oxo complex, yielding a
      lower limit of 7.85 eV for the ionization energy of gaseous [(tpfpp)Mn(IV)O].
      Linear free-energy analyses of the reactions of para-substituted N,N
      dimethylanilines and thioanisoles indicate that a considerable amount of positive
      charge is developed on the heteroatom in the oxidation transition state.
      Substrates endowed with different heteroatoms, but similar ionization energy
      display a comparable reaction efficiency, consistent with a mechanism initiated
      by ET. For the first time, the kinetic acidity of putative hydroxo intermediates
      playing a role in catalytic oxidations, [(tpfpp)Fe(IV)OH](+) and
      [(tpfpp)Mn(IV)OH](+), has been investigated with selected reference bases,
      revealing a comparatively higher basicity for the ferryl, [(tpfpp)Fe(IV)O], with
      respect to the manganyl, [(tpfpp)Mn(IV)O], unit. Finally, the neat association
      reaction of 2 has been studied with various ligands showing that harder ligands
      are more strongly bound.

PMID- 21905136
TI  - Calcium-mediated dearomatization, C-H bond activation, and allylation of
      alkylated and benzannulated pyridine derivatives.
AB  - A facile and general synthetic pathway for the production of dearomatized,
      allylated, and C-H bond activated pyridine derivatives is presented. Reaction of
      the corresponding derivative with the previously reported reagent
      bis(allyl)calcium, [Ca(C(3)H(5))(2)] (1), cleanly affords the product in high
      yield. The range of N-heterocyclic compounds studied comprised 2-picoline (2), 4
      picoline (3), 2,6-lutidine (4), 4-tert-butylpyridine (5), 2,2'-bipyridine (6),
      acridine (7), quinoline (8), and isoquinoline (9). Depending on the substitution
      pattern of the pyridine derivative, either carbometalation or C-H bond activation
      products are obtained. In the absence of methyl groups ortho or para to the
      nitrogen atom, carbometalation leads to dearomatized products. C(sp(3))-H bond
      activation occurs at ortho and para situated methyl groups. Steric shielding of
      the 4-position in pyridine yields the ring-metalated product through C(sp(2))-H
      bond activation instead. The isolated compounds [Ca(2-CH(2)-C(5)H(4)N)(2)(THF)]
      (2b?(THF)), [Ca(4-CH(2)-C(5)H(4)N)(2)(THF)(2)] (3b?(THF)(2)), [Ca(2-CH(2)
      C(5)H(3)N-6-CH(3))(2)(THF)(n)] (4b?(THF)(n); n=0, 0.75), [Ca{2-C(5)H(3)N-4
      C(CH(3))(3)}(2)(THF)(2)] (5c?(THF)(2)), [Ca{4,4'-(C(3)H(5))(2)
      (C(10)H(8)N(2))}(THF)] (6a?(THF)), [Ca(NC(13) H(9)-9-C(3)H(5))(2)(THF)]
      (7a?(THF)), [Ca(4-C(3) H(5)-C(9) H(7)N)(2)(THF)] (8b?(THF)), and [Ca(1-C(3)H(5)
      C(9)H(7) N)(2)(THF)(3)] (9a?(THF)(3)) have been characterized by NMR spectroscopy
      and metal analysis. 9a?(THF)(4) and 4b?(THF)(3) were additionally characterized
      in the solid state by X-ray diffraction experiments. 4b?(THF)(3) shows an aza
      allyl coordination mode in the solid state. Based on the results, mechanistic
      aspects are discussed in the context of previous findings.

PMID- 21905138
TI  - Sterically demanding hetero-substituted [2]borametallocenophanes of group IV
      metals: synthesis, structure and reactivity.
AB  - We report the synthesis and characterisation of unprecedented unstrained
      [2]diborametallocenophanes of zirconium and hafnium that bear the bulky
      octamethylfluorenyl (eta(5)-C(29)H(36)) system, the proligands of which were pre
      constructed by a two-step synthesis. The compounds were fully characterised by
      NMR spectroscopy, MALDI-TOF mass spectrometry and X-ray diffraction analysis.
      Typical reactivities relevant to olefin polymerisation such as methylation and
      chloride abstraction were also investigated. Finally, a sterically demanding
      bis(octamethylfluorenyl) metallocene was prepared.

PMID- 21905137
TI  - Spiropyran-amidine: a molecular canary for visual detection of carbon dioxide
      gas.

PMID- 21905139
TI  - Autoinductive exponential signal amplification: a diagnostic probe for direct
      detection of fluoride.
AB  - A new example of an exponential signal amplification strategy for the direct
      detection of fluoride is demonstrated. The amplification occurred through
      reaction of fluoride with a responsive chromogenic probe. The probe activity is
      based on a unique dendritic chain reaction that generates a fluoride anion, which
      is the analyte of interest, during the disassembly pathway of the dendritic
      probe. This autoinductive amplification mechanism may be applied for detection of
      other analytes by coupling activity of a modified probe with that of the fluoride
      amplifier.

PMID- 21905140
TI  - Oxidation state changes and electron flow in enzymatic catalysis and
      electrocatalysis through Wannier-function analysis.
AB  - In catalysis by metalloenzymes and in electrocatalysis by clusters related in
      structure and composition to the active components of such enzymes transition
      metal atoms can play a central role in the catalyzed redox reactions. Changes to
      their oxidation states (OSs) are critical for understanding the reactions. The OS
      is a local property and we introduce a new, generally useful local method for
      determining OSs, their changes, and the associated bonding changes and electron
      flow. The method is based on computing optimally localized orbitals (OLOs). With
      this method, we analyze two cases, superoxide reductase (SOR) and a proposed
      hydrogen-producing model electrocatalyst [FeS(2)]/[FeFe](P), a modification of
      the active site of the diiron hydrogenase enzymes. Both utilize an under
      coordinated Fe site where a one-electron reduction (for SOR) or a two-electron
      reduction (for [FeFe](P)) of the substrate occurs. We obtain the oxidation states
      of the Fe atoms and of their critical ligands, the changes of the bonds to those
      ligands, and the electron flow during the catalytic cycle, thereby demonstrating
      that OLOs constitute a powerful interpretive tool for unraveling reaction
      mechanisms by first-principles computations.

PMID- 21905141
TI  - Highly luminescent octanuclear Au(I)-Cu(I) clusters adopting two structural
      motifs: the effect of aliphatic alkynyl ligands.
AB  - Reactions of the homoleptic (AuC(2)R)(n) precursors with stoichiometric amount of
      diphosphine ligand PPh(2)C(6)H(4)PPh(2) (P^P) and Cu(+) ions lead to an assembly
      of a new family of bimetallic clusters [Au(6)Cu(2)(C(2)R)(6)(P^P)(2)](2+) (type
      I; R=9-fluorenolyl (1), diphenylmethanolyl (2), 2,6-dimethyl-4-heptanolyl (3), 1
      cyclohexanolyl (4), Cy (5), tBu (6)). In the case of R=1-cyclohexanolyl, a
      structurally different complex [Au(6)Cu(2)(C(2)C(6)H(11)O)(6)(P^P)(3)](2+) (7,
      type II) could be obtained by treatment of 4 with one equivalent of the
      diphosphine, while for R=isopropanolyl only the latter type of cluster
      [Au(6)Cu(2)(C(2)C(3)H(7)O)(6)(P^P)(3)](2+) (8) was detected. Steric bulkiness of
      the alkynyl ligands and O...H-O hydrogen bonding are suggested to play an
      important role in stabilizing the type I and type II cluster structural motif,
      respectively. All the complexes exhibit intense photoluminescence in solution
      with emission parameters that depending on the geometrical arrangement of the
      octanuclear metal core. The clusters 1-4 and 6 show single emission band in a
      blue region (469-488 nm) with maximum quantum yield of 94% (4), while
      structurally different 7 and 8 emit yellow-orange (590 nm) with unity quantum
      efficiency. The theoretical DFT calculations of the electronic structures have
      been carried out to demonstrate that the metal-centered triplet emission within
      the heterometallic core plays a key role for the observed phosphorescence.

PMID- 21905142
TI  - Proton-coupled electron transfer originating from excited states of luminescent
      transition-metal complexes.
AB  - Proton-coupled electron transfer (PCET) is of fundamental importance for small
      molecule activation processes, such as water splitting, CO(2)-reduction, or
      nitrogen fixation. Ideally, energy-rich molecules such as H(2), CH(3)OH, or NH(3)
      could be generated artificially using (solar) light as an energy input. In this
      context, PCETs originating directly from electronically excited states play a
      crucial role. A variety of transition-metal complexes have been used recently for
      fundamental investigations of this important class of reactions, and the key
      findings of these studies are reviewed in this article. The present minireview
      differs from other reviews on the subject of PCET in that it focuses specifically
      on reactions occurring directly from electronically excited states.

PMID- 21905143
TI  - Controlling thermally induced electron transfer in cyano-bridged molecular
      squares: from solid state to solution.

PMID- 21905144
TI  - Methane activation by yttrium-doped vanadium oxide cluster cations: local charge
      effects.

PMID- 21905145
TI  - Free radical reactivity of mono- and dichlorosilylene with muonium.

PMID- 21905148
TI  - A novel polymeric chemosensor: dual colorimetric detection of metal ions through
      click synthesis.
AB  - A highly colored polystyrene derivative bearing side chain chromophores composed
      of dialkylanilino donor and cyano-based acceptor groups, prepared by atom
      economic click postfunctionalization, displays the dual colorimetric detection
      behavior of several metal ions based on the specific interactions with different
      nitrogen atoms. Hard to borderline metal ions, such as Fe(3+) , Fe(2+) , and
      Sn(2+) , are always recognized by the dialkylanilino nitrogen atom, resulting in
      a decrease in the charge-transfer (CT) band intensity of the donor-acceptor
      chromophores. On the other hand, the recognition site of a soft metal ion of
      Ag(+)  is the cyano nitrogen atom due to the readily formed multivalent
      coordination, which produces a bathochromic shift of the CT band.

PMID- 21905150
TI  - The effects of insurance mandates on choices and outcomes in infertility
      treatment markets.
AB  - For the 10% to 15% of American married couples who experience reproductive
      problems, in vitro fertilization (IVF) is the leading technologically advanced
      treatment procedure. However, IVF's expense may prevent many couples from
      receiving treatment, and those who are treated may take an overly aggressive
      approach to reduce the probability of failure. Aggressive treatment, which occurs
      through an increase in the number of embryos transferred during IVF, can lead to
      medically dangerous multiple births. We evaluated the principle policy proposal
      insurance mandates-for improving IVF access and outcomes. We used data from US
      markets during 1995-2003 to show that broad insurance mandates for IVF result in
      not only large increases in treatment access but also significantly less
      aggressive treatment. More limited insurance mandates, which may apply to a
      subset of insurers or provide weaker guidelines for insurer behavior, generally
      have little effect on IVF markets.

PMID- 21905149
TI  - Neutralizing human monoclonal antibodies to severe acute respiratory syndrome
      coronavirus: target, mechanism of action, and therapeutic potential.
AB  - The emergence of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) led to
      a rapid response not only to contain the outbreak but also to identify possible
      therapeutic interventions, including the generation of human monoclonal
      antibodies (hmAbs). hmAbs may be used therapeutically without the drawbacks of
      chimeric or animal Abs. Several different methods have been used to generate SARS
      CoV specific neutralizing hmAbs including the immunization of transgenic mice,
      cloning of small chain variable regions from naive and convalescent patients, and
      the immortalization of convalescent B cells. Irrespective of the techniques used,
      the majority of hmAbs specifically reacted with the receptor binding domain (RBD)
      of the spike (S) protein and likely prevented receptor binding. However, several
      hmAbs that can bind to epitopes either within the RBD, located N terminal of the
      RBD or in the S2 domain, and neutralize the virus with or without inhibiting
      receptor binding have been identified. Therapeutic utility of hmAbs has been
      further elucidated through the identification of potential combinations of hmAbs
      that could neutralize viral variants including escape mutants selected using
      hmAbs. These results suggest that a cocktail of hmAbs that can bind to unique
      epitopes and have different mechanisms of action might be of clinical utility
      against SARS-CoV infection, and indicate that a similar approach may be applied
      to treat other viral infections.

PMID- 21905151
TI  - The role of private medical insurance in socio-economic inequalities in cancer
      screening uptake in Ireland.
AB  - Screening is seen by many as a key element in cancer control strategies.
      Differences in uptake of screening related to socio-economic status exist and may
      contribute to differences in morbidity and mortality across socio-economic
      groups. Although a number of factors are likely to underlie differential uptake,
      differential access to subsequent diagnostic tests and/or treatment may have a
      pivotal role. This study examines differences in the uptake of cancer screening
      in Ireland related to socio-economic status. Data were extracted from SLAN 2007
      concerning uptake of breast, cervical, colorectal and prostate cancer screening
      in the preceding 12 months. Concentration indices were calculated and decomposed.
      Particular emphasis was placed in the decomposition upon the impact of private
      health insurance, evidenced in other work to impact on access to care within the
      mixed public-private Irish health system. This study found that significant
      differences related to socio-economic status exist with respect to uptake of
      cancer screening and that the main determinant of difference for breast,
      colorectal and prostate cancer screening was possession of private insurance.
      This may have profound implications for the design of cancer control strategies
      in countries where private insurance has a significant role, even where screening
      services are publicly funded and population based.

PMID- 21905152
TI  - Spoilt for choice: implications of using alternative methods of costing hospital
      episode statistics.
AB  - In the absence of a 'gold standard' to estimate the economic burden of disease, a
      decision about the most appropriate costing method is required. Researchers have
      employed various methods to cost hospital stays, including per diem or diagnosis
      related group (DRG)-based costs. Alternative methods differ in data collection
      and costing methodology. Using data from Scotland as an illustrative example,
      costing methods are compared, highlighting the wider implications for other
      countries with a publicly financed healthcare system. Five methods are compared
      using longitudinal data including baseline survey data (Midspan) linked to acute
      hospital admissions. Cost variables are derived using two forms of DRG-type
      costs, costs per diem, costs per episode-using a novel approach that
      distinguishes between variable and fixed costs and incorporates individual length
      of stay (LOS), and costs per episode using national average LOS. Cost estimates
      are generated using generalised linear model regression. Descriptive analysis
      shows substantial variation between costing methods. Differences found in
      regression analyses highlight the magnitude of variation in cost estimates for
      subgroups of the sample population. This paper emphasises that any inference made
      from econometric modelling of costs, where the marginal effect of explanatory
      variables is assessed, is substantially influenced by the costing method.

PMID- 21905153
TI  - Quality of life, treatments, and patients' willingness to pay for a complete
      remission of cervical cancer in Taiwan.
AB  - Cervical cancer is one of the leading causes of cancer deaths in Taiwan. To
      investigate the disease cost and then raise awareness of the importance of
      screening for cervical cancer and promote early detection, this paper employs
      contingent valuation and willingness to pay (WTP) method to study how health
      related quality of life, disease severity, and after-treatment disease status
      affect patients' WTP for a complete remission of the disease. The inclusive
      criteria for the study were primary case outpatients at least 3 months after they
      had received therapy at the time of our study period. Face-to-face interviews
      were conducted for the retrospective format of the survey. The result of the
      study indicates a lifetime WTP of $US21 221.96 for Taiwanese cervical cancer
      patients, which is significantly higher than the cost of screening for early
      detection. Disease stages do not show a consistent pattern in influencing WTP,
      but patients with surgery are willing to pay a significantly higher amount for a
      complete remission from the disease than patients without. In addition, mental
      health, positive attitudes toward life, and quality of life also are key factors
      that influence WTP.

PMID- 21905154
TI  - The effect of Taiwan's national health insurance on mortality of the elderly:
      revisited.
AB  - A recent paper estimates the effects of Taiwan's National Health Insurance (NHI)
      on the elderly and concludes that NHI greatly increased the medical care
      utilization of the elderly but did not reduce their mortality. Using more recent
      and more accurate mortality data of the same group of elderly, this note re
      estimates the NHI effect on mortality and finds that the mortality hazard of the
      previously uninsured elderly in the post-NHI period was on average 24% lower than
      it would have been in the absence of NHI. However, the NHI effect on the
      mortality hazard is only evident in the first 6 years following the enactment of
      NHI, suggesting that it may be difficult to undo the damage caused by the lack of
      insurance in early life.

PMID- 21905155
TI  - Use of psychotropic medications by US cancer survivors.
AB  - OBJECTIVES: This study aimed to describe national utilization of psychotropic
      medications by adult cancer survivors in the USA and to estimate the extra use of
      psychotropic medications that is attributable to cancer survivorship. METHODS:
      Prescription data for 2001-2006 from the Medical Expenditure Panel Survey (MEPS)
      were linked to the data identifying cancer survivors from the National Health
      Interview Survey, the MEPS sampling frame. The sample was limited to adults 25
      years of age and older. Propensity score matching was used to estimate the
      effects of cancer survivorship on utilization of psychotropic medications by
      comparing cancer survivors and other adults in MEPS. Utilization was measured as
      any use during a calendar year and the number of prescriptions purchased
      (including refills). Analyses were stratified by gender and age, distinguishing
      adults younger than 65 years from those 65 years and older. RESULTS: Nineteen
      percent of cancer survivors under age 65 years and 16% of survivors age 65 years
      and older used psychotropic medications. Sixteen percent of younger survivors
      used antidepressants, 7% used antianxiety medications. For older survivors,
      utilization rates for these two drug types were 11% and 7%, respectively. The
      increase in any use attributable to cancer amounted to 4-5 percentage points for
      younger survivors (p < 0.05) and 2-3 percentage points for older survivors (p <
      0.05), depending on gender. CONCLUSION: Increased use of psychotropic medications
      by cancer survivors, compared with other adults, suggests that survivorship
      presents ongoing psychological challenges.

PMID- 21905156
TI  - Perceptions of prostate cancer in Black African and Black Caribbean men: a
      systematic review of the literature.
AB  - BACKGROUND: Prostate cancer (PC) is common and affects Black African and
      Caribbean men disproportionately more than White men. It is known that PC
      awareness is low in these groups, but knowledge is lacking about other factors
      that may deter Black men from seeking information about, or getting tested for,
      PC. The aim of this review was to appraise research on knowledge and perceptions
      of PC among Black men. METHODS: Four medical and social science databases were
      systematically searched, and reference lists of relevant papers were hand
      searched. Non-English publications were excluded. Qualitative findings were
      synthesised using comparative thematic analysis to which quantitative findings
      were integrated. RESULTS: Thirteen qualitative studies and 20 cross-sectional
      surveys were included. All except two were conducted in the USA. The analysis
      identified individual, cultural and social factors likely to impact on Black
      men's awareness of, and willingness to be tested for, PC. Black men's awareness
      of personal risk of PC varied greatly between studies. Misunderstandings
      regarding methods of diagnosis and treatment were widespread. PC testing and
      treatment were perceived as a threat to men's sense of masculinity. Mistrust of
      the health-care system, limited access to health care and lack of trusting
      relationships with health professionals were also prominent. CONCLUSION: The
      factors impacting on Black men's awareness of PC may contribute to late PC
      diagnosis and should be taken into account when communicating with Black men
      seeking prostate care. Further, the review demonstrated a need for high-quality
      studies in countries other than the USA to determine the relevance of the review
      findings for Black men in other nations and continents.

PMID- 21905157
TI  - Refinement of the distress management problem list as the basis for a holistic
      therapeutic conversation among UK patients with cancer.
AB  - OBJECTIVE: Originally devised in the USA, the Distress Thermometer is being
      deployed in many cancer settings in the UK. It is commonly used with a Problem
      List (PL), which has never been validated with a UK population. This study aimed
      to refine the PL items based upon the concerns of a sample of UK patients
      attending a regional cancer centre. METHODS: Existing versions of the PL were
      scrutinised by a focus group comprising five ex-patients, six health care staff
      and two academics. This group considered the intelligibility, ambiguity and
      redundancy of items, sometimes making alternative suggestions or pooling items.
      The resulting 46 candidate items were sent to 735 patients with mixed cancer,
      asking them to endorse items that had been 'a source of concern or distress'
      during their recently finished treatment. We used multivariate logistic
      regression to evaluate the association between the prevalence of problems and
      patient characteristics. RESULTS: In this study, 395 (53%) people responded.
      'Fatigue, exhaustion or extreme tiredness' (70%), 'worry, fear or anxiety' (45%)
      and 'sleep problems' (38%) were the most frequently endorsed items. Items not
      appearing on the original PL were commonly endorsed such as 'memory or
      concentration' (30%) and 'loneliness or isolation' (15%), suggesting that they
      should be routinely included in the Distress Thermometer Problem List.
      CONCLUSIONS: The current study offers a more comprehensive PL, on the basis of
      actual patients' concerns, using words that are understood by UK patients. The
      reluctance of some patients to volunteer their concerns suggests that screening
      for distress should be undertaken within the context of a structured
      conversation.

PMID- 21905158
TI  - Home-based physical activity intervention for colorectal cancer survivors.
AB  - BACKGROUND: The efficacy of a home-based physical activity (PA) intervention for
      colorectal cancer patients versus contact control was evaluated in a randomized
      controlled trial. METHODS: Forty-six patients (mean age = 57.3 years [SD = 9.7],
      57% female, mean = 2.99 years post-diagnosis [SD = 1.64]) who had completed
      treatment for stages 1-3 colorectal cancer were randomized to telephone
      counseling to support PA (PA group, n = 20) or contact control (control group, n
      = 26). PA group participants received 3 months of PA counseling (based on the
      transtheoretical model and the social cognitive theory) delivered via telephone,
      as well as weekly PA tip sheets. Assessments of PA (Seven-day Physical Activity
      Recall [7-day PAR] and Community Healthy Activities Model Program for Seniors
      [CHAMPS]), submaximal aerobic fitness (Treadwalk test), motivational readiness
      for PA, and psychosocial outcomes were conducted at baseline, 3, 6, and 12 months
      post-baseline. Objective accelerometer data were collected at the same time
      points. RESULTS: The PA group reported significant increases in minutes of PA at
      3 months (7-day PAR) and caloric expenditure (CHAMPS) compared with the control
      group, but the group differences were attenuated over time. The PA group showed
      significant improvements in fitness at 3, 6, and 12 months versus the control
      group. Improvements in motivational readiness for PA were reported in the PA
      group only at 3 months. No significant group differences were found for fatigue,
      self-reported physical functioning, and quality of life at 3, 6, and 12 months.
      CONCLUSION: A home-based intervention improved survivors' PA and motivational
      readiness at 3 months and increased submaximal aerobic fitness at 3, 6, and 12
      months.

PMID- 21905159
TI  - Oral contraceptive use in women at increased risk of breast/ovarian cancer:
      knowledge and attitudes.
AB  - BACKGROUND: Several of the health benefits and risks associated with the combined
      oral contraceptive pill (COCP) are particularly relevant to women at risk of
      hereditary breast and/or ovarian cancer. METHODS: Eighty-three past female
      patients of an Australian hereditary cancer clinic aged 18-50 years completed a
      self-report questionnaire to assess their contraceptive practices, knowledge and
      information needs (44% response rate). RESULTS: Ninety-two percent of
      participants had previously used the COCP, with a mean knowledge score of 3.63
      out of 8. Nearly 40% reported that their family history of cancer was one reason
      they discontinued/avoided using the COCP. Women reported receiving insufficient
      COCP information and preferred a targeted information leaflet to answer their
      questions. CONCLUSIONS: Although recall bias may have affected some women, there
      is a clear need to improve the consistency of information delivered to women at
      risk of hereditary breast and/or ovarian cancer, to ensure informed contraceptive
      choices are made.

PMID- 21905160
TI  - Partners and close family members of long-term cancer survivors: health status,
      psychosocial well-being and unmet supportive care needs.
AB  - BACKGROUND: A cancer diagnosis can have a profound impact on partners and close
      family members of patients. Little is currently known about the long-term impact.
      OBJECTIVES: The objective of this study is to describe health status, levels of
      anxiety and depression, unmet supportive care needs and positive outcomes in the
      partners/family members of breast, prostate and colorectal cancer survivors 5-16
      years post-diagnosis. METHODS: Patients in a linked study were asked to invite a
      partner or other close family member to complete a self-administered postal
      questionnaire. Data were analysed by cancer site and time since diagnosis.
      Matched comparisons were made between cancer patients in the linked study and
      their partners. RESULTS: An expression of interest was received from 330
      partners/family members, and 257 questionnaires (77.9%) were returned. Health
      status and levels of anxiety and depression were comparable with population
      norms. Respondents reported an average of 2.7 unmet needs from 34 possible
      options. Hospital parking, information about familial risk, help managing fear of
      recurrence and coordination of care were the most cited unmet needs. There was
      little variation in health status, psychological morbidity and unmet needs by
      cancer site or time since diagnosis. Concordance between patients and partners
      was low for anxiety but higher with respect to positive outcomes and some unmet
      needs. CONCLUSIONS: Most partners/family members of long-term cancer survivors
      report few ongoing issues. However, a small proportion (<10%) have high levels of
      anxiety and/or moderate or strong unmet needs. Strategies for identifying this
      group and addressing their needs are required, while allowing the majority to
      resume normal life.

PMID- 21905161
TI  - Have a little faith: measuring the impact of illness on positive and negative
      aspects of faith.
AB  - BACKGROUND: The importance of faith and its associations with health are well
      documented. As part of the Patient Reported Outcomes Measurement Information
      System, items tapping positive and negative impact of illness (PII and NII) were
      developed across four content domains: Coping/Stress Response, Self-Concept,
      Social Connection/Isolation, and Meaning and Spirituality. Faith items were
      included within the concept of meaning and spirituality. METHODS: This
      measurement model was tested on a heterogeneous group of 509 cancer survivors. To
      evaluate dimensionality, we applied two bi-factor models, specifying a general
      factor (PII or NII) and four local factors: Coping/Stress Response, Self-Concept,
      Social Connection/Isolation, and Meaning and Spirituality. RESULTS: Bi-factor
      analysis supported sufficient unidimensionality within PII and NII item sets. The
      unidimensionality of both PII and NII item sets was enhanced by extraction of the
      faith items from the rest of the questions. Of the 10 faith items, nine
      demonstrated higher local than general factor loadings (range for local factor
      loadings = 0.402 to 0.876), suggesting utility as a separate but related 'faith'
      factor. The same was true for only two of the remaining 63 items across the PII
      and NII item sets. CONCLUSIONS: Although conceptually and to a degree empirically
      related to Meaning and Spirituality, Faith appears to be a distinct subdomain of
      PII and NII, better handled by distinct assessment. A 10-item measure of the
      impact of illness upon faith (II-Faith) was therefore assembled.

PMID- 21905162
TI  - Getting back on track: evaluation of a brief group psychoeducation intervention
      for women completing primary treatment for breast cancer.
AB  - OBJECTIVE: Patients with breast cancer experience unmet informational and
      psychosocial needs at the end of treatment. A brief psychoeducational
      intervention delivered at this transition may help to address some of the
      challenges these women face. The purpose of this study was to test the
      effectiveness of a single-session group psychoeducational intervention (GBOT
      group) compared with standard print material (usual care). METHODS: In this
      randomized controlled trial, 442 patients with breast cancer who were completing
      their adjuvant radiotherapy were recruited and randomized to receive either usual
      care, which includes standard print material (CRL group n = 226) or usual care
      and the GBOT group intervention (INT group n = 216). Participants completed
      measures at baseline and again at 3 and 6 months post-intervention. RESULTS: The
      INT group showed significant improvement in their knowledge regarding the re
      entry transition period (d = 0.31) and in their feelings of preparedness for re
      entry (d = 0.37). There were no differences between the groups over time on
      health-related distress or mood. CONCLUSIONS: Results support the effectiveness
      of providing a single-session group psychoeducational intervention as a first
      step approach to supportive care for women at the end of breast cancer treatment.

PMID- 21905163
TI  - A high-resolution molecular atlas of the fetal mouse lower urogenital tract.
AB  - Epithelial-stromal interactions in the lower urogenital tract (LUT) are integral
      to prostatic and seminal vesicle development in males, vaginal and uterine
      development in females, and urethral development in both sexes. Gene expression
      profiling of isolated LUT stroma and epithelium has unraveled mechanisms of LUT
      development, but such studies are confounded by heterogeneous and ill-defined
      cell sub-populations contained within each tissue compartment. We used in situ
      hybridization to synthesize a high-resolution molecular atlas of 17-day post
      coitus fetal mouse LUT. We identified mRNAs that mark selective cell populations
      of the seminal vesicle, ejaculatory duct, prostate, urethra, and vagina,
      subdividing these tissues into 16 stromal and 8 epithelial sub-compartments.
      These results provide a powerful tool for mapping LUT gene expression patterns
      and also reveal previously uncharacterized sub-compartments that may play
      mechanistic roles in LUT development of which we were previously unaware.

PMID- 21905164
TI  - Gal80 intersectional regulation of cell-type specific expression in vertebrates.
AB  - Characterization and functional manipulation of specific groups of neurons in the
      vertebrate central nervous system (CNS) remains a major hurdle for understanding
      complex circuitry and functions. In zebrafish, the Gal4/UAS system has permitted
      expression of transgenes and enhancer trap screens, but is often limited by broad
      expression domains. We have developed a method for cell-type specific expression
      using Gal80 inhibition of Gal4-dependent expression. We show that native Gal4 is
      able to drive strong expression, that Gal80 can inhibit this expression, and that
      overlapping Gal4 and Gal80 expression can achieve "intersectional" expression in
      spatially and genetically defined subsets of neurons. We also optimize Gal80 for
      expression in vertebrates, track Gal80 expression with a co-expressed fluorescent
      marker, and use a temperature-sensitive allele of Gal80 to temporally regulate
      its function. These data demonstrate that Gal80 is a powerful addition to the
      genetic techniques available to map and manipulate neural circuits in zebrafish.

PMID- 21905166
TI  - Comprehensive mutation analysis (20 families) of the choroideremia gene reveals a
      missense variant that prevents the binding of REP1 with Rab geranylgeranyl
      transferase.
AB  - Choroideremia (CHM), an X-linked degeneration of the retinal pigmented epithelium
      (RPE), photoreceptors, and choroid, ultimately leads to blindness. It is caused
      by loss-of-function of the CHM gene product, the Rab escort protein 1 (REP1) that
      is involved, together with its homologue REP2, in prenylation of Rab GTPases, key
      regulators of intracellular vesicular traffic. Here, we report the molecular
      characterization of 20 unrelated Italian families affected by CHM. We identified
      19 different mutations, nine of which are new. In most cases, we analyzed the
      effect of the mutations at the mRNA level. Furthermore, we demonstrated, by in
      vitro trancription/translation assays, that the mutated mRNAs produced truncated
      proteins in all cases but one. In fact, we also identified a novel REP1 missense
      variant (c.1520A>G; p.H507R) associated to CHM. Thus far, only two other CHM
      associated missense mutations have been identified, one of which was a splicing
      alteration. We investigated the impact of the p.H507R amino acid change on REP1
      structure and function, thus providing the first experimental demonstration that
      correlates a missense mutation in CHM with a functional impairment of REP1.
      Overall, our results indicate that the REP1-Rab geranyl-geranyl transferase
      interaction and consequently REP1-mediated Rab prenylation is essential for RPE
      and photoreceptor function.

PMID- 21905165
TI  - The tight junction scaffolding protein cingulin regulates neural crest cell
      migration.
AB  - Neural crest cells give rise to a diverse range of structures during vertebrate
      development. These cells initially exist in the dorsal neuroepithelium and
      subsequently acquire the capacity to migrate. Although studies have documented
      the importance of adherens junctions in regulating neural crest cell migration,
      little attention has been paid to tight junctions during this process. We now
      identify the tight junction protein cingulin as a key regulator of neural crest
      migration. Cingulin knock-down increases the migratory neural crest cell domain,
      which is correlated with a disruption of the neural tube basal lamina.
      Overexpression of cingulin also augments neural crest cell migration and is
      associated with similar basal lamina changes and an expansion of the premigratory
      neural crest population. Cingulin overexpression causes aberrant ventrolateral
      neuroepithelial cell delamination, which is linked to laminin loss and a decrease
      in RhoA. Together, our results highlight a novel function for cingulin in the
      neural crest.

PMID- 21905167
TI  - DominantMapper: rule-based analysis of SNP data for rapid mapping of dominant
      diseases in related nuclear families.
AB  - With the advent of cheap rapid methods for whole-genome SNP genotyping and the
      completion of the Human Genome Project, mapping disease loci has become primarily
      a bioinformatic rather than a laboratory problem. Here, we describe
      DominantMapper, a computer program that implements a rule-based analysis
      algorithm for the detection of dominant disease loci in either a small number of
      nuclear families or a single large nuclear family. To demonstrate its utility, we
      present the successful analysis of two pedigrees in which the affected
      individuals carry either APC or TSPAN12 mutations.

PMID- 21905168
TI  - Molecular cloaking of H2A.Z on mortal DNA chromosomes during nonrandom
      segregation.
AB  - Although nonrandom sister chromatid segregation is a singular property of
      distributed stem cells (DSCs) that are responsible for renewing and repairing
      mature vertebrate tissues, both its cellular function and its molecular mechanism
      remain unknown. This situation persists in part because of the lack of facile
      methods for detecting and quantifying nonrandom segregating cells and for
      identifying chromosomes with immortal DNA strands, the cellular molecules that
      signify nonrandom segregation. During nonrandom segregation, at each mitosis,
      asymmetrically self-renewing DSCs continuously cosegregate to themselves the set
      of chromosomes that contain immortal DNA strands, which are the oldest DNA
      strands. Here, we report the discovery of a molecular asymmetry between
      segregating sets of immortal chromosomes and opposed mortal chromosomes (i.e.,
      containing the younger set of DNA template strands) that constitutes a new
      convenient biomarker for detection of cells undergoing nonrandom segregation and
      direct delineation of chromosomes that bear immortal DNA strands. In both cells
      engineered with DSC-specific properties and ex vivo-expanded mouse hair follicle
      stem cells, the histone H2A variant H2A.Z shows specific immunodetection on
      immortal DNA chromosomes. Cell fixation analyses indicate that H2A.Z is present
      on mortal chromosomes as well but is cloaked from immunodetection, and the
      cloaking entity is acid labile. The H2A.Z chromosomal asymmetry produced by
      molecular cloaking provides a first direct assay for nonrandom segregation and
      for chromosomes with immortal DNA strands. It also seems likely to manifest an
      important aspect of the underlying mechanism(s) responsible for nonrandom sister
      chromatid segregation in DSCs.

PMID- 21905169
TI  - Vascular endothelial growth factor stimulates endothelial colony forming cells
      proliferation and tubulogenesis by inducing oscillations in intracellular Ca2+
      concentration.
AB  - Endothelial progenitor cells (EPCs) home from the bone marrow to the site of
      tissue regeneration and sustain neovascularization after acute vascular injury
      and upon the angiogenic switch in solid tumors. Therefore, they represent a
      suitable tool for cell-based therapy (CBT) in regenerative medicine and provide a
      novel promising target in the fight against cancer. Intracellular Ca(2+) signals
      regulate numerous endothelial functions, such as proliferation and tubulogenesis.
      The growth of endothelial colony forming cells (ECFCs), which are EPCs capable of
      acquiring a mature endothelial phenotype, is governed by store-dependent Ca(2+)
      entry (SOCE). This study aimed at investigating the nature and the role of VEGF
      elicited Ca(2+) signals in ECFCs. VEGF induced asynchronous Ca(2+) oscillations,
      whose latency, amplitude, and frequency were correlated to the growth factor
      dose. Removal of external Ca(2+) (0Ca(2+)) and SOCE inhibition with N-(4-[3,5
      bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl)-4-methyl-1,2,3-thiadiazole-5
      carboxamide (BTP-2) reduced the duration of the oscillatory signal. Blockade of
      phospholipase C-gamma with U73122, emptying the inositol-1,4,5-trisphosphate
      (InsP(3))-sensitive Ca(2+) pools with cyclopiazonic acid (CPA), and inhibition of
      InsP(3) receptors with 2-APB prevented the Ca(2+) response to VEGF. VEGF-induced
      ECFC proliferation and tubulogenesis were inhibited by the Ca(2+)-chelant, BAPTA,
      and BTP-2. NF-kappaB activation by VEGF was impaired by BAPTA, BTP-2, and its
      selective blocker, thymoquinone. Thymoquinone, in turn, suppressed VEGF-dependent
      ECFC proliferation and tubulogenesis. These data indicate that VEGF-induced
      Ca(2+) oscillations require the interplay between InsP(3)-dependent Ca(2+)
      release and SOCE, and promote ECFC growth and tubulogenesis by engaging NF
      kappaB. This novel signaling pathway might be exploited to enhance the outcome of
      CBT and chemotherapy.

PMID- 21905171
TI  - Response to Clarke K, Regueiro M. Stopping immunomodulators and biologics in
      inflammatory bowel disease patients in remission. Inflamm Bowel Dis 2011 [Epub
      ahead of print].

PMID- 21905170
TI  - Concise review: Human cell engineering: cellular reprogramming and genome
      editing.
AB  - Cell engineering is defined here as the collective ability to both reset and edit
      the genome of a mammalian cell. Until recently, this had been extremely
      challenging to achieve as nontransformed human cells are significantly refractory
      to both these processes. The recent success in reprogramming somatic cells into
      induced pluripotent stem cells that are self-renewable in culture, coupled with
      our increasing ability to effect precise and predesigned genomic editing, now
      readily permits cellular changes at both the genetic and epigenetic levels. These
      dual capabilities also make possible the generation of genetically matched,
      disease-free stem cells from patients for regenerative medicine. The objective of
      this review is to summarize the key enabling developments on these two rapidly
      evolving research fronts in human cell engineering, highlight unresolved issues,
      and outline potential future research directions.

PMID- 21905176
TI  - Reliable and efficient procedures for the conjugation of biomolecules through
      Huisgen azide-alkyne cycloadditions.
AB  - The Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) has been established as a
      powerful coupling technology for the conjugation of proteins, nucleic acids, and
      polysaccharides. Nevertheless, several shortcomings related to the presence of
      Cu, mainly oxidative degradation by reactive oxygen species and sample
      contamination by Cu, have been pointed out. This Minireview discusses key aspects
      found in the development of the efficient and benign functionalization of
      biomacromolecules through CuAAC, as well as the Cu-free strain-promoted azide
      alkyne cycloaddition (SPAAC).

PMID- 21905177
TI  - Developing synthetic approaches with non-innocent metalloligands: easy access to
      Ir(I)/Pd(0) and Ir(I)/Pd(0)/Ir(I) cores.

PMID- 21905173
TI  - Comparative cost-effectiveness of strategies to prevent postoperative clinical
      recurrence of Crohn's disease.
AB  - BACKGROUND: A number of treatments have been shown to reduce the risk of
      postoperative recurrence of Crohn's disease (CD). The optimal strategy is
      unknown. The aim was to evaluate the comparative cost-effectiveness of
      postoperative strategies to prevent clinical recurrence of CD. METHODS: Three
      prophylactic strategies were compared to "no prophylaxis"; mesalamine,
      azathioprine (AZA) / 6-mercaptopurine (6-MP), and infliximab. The probability of
      clinical recurrence, endoscopic recurrence, and therapy discontinuation due to
      adverse drug reactions (ADRs) were extracted from randomized controlled trials
      (RCTs). Quality-of-life scores and treatment costs were derived from published
      data. The primary model evaluated quality-adjusted life years (QALYs) and cost
      effectiveness at 1 year after surgery. Sensitivity analysis assessed the impact
      of a range of recurrence rates on cost-effectiveness. An exploratory analysis
      evaluated cost-effectiveness outcomes 5 years after surgery. RESULTS: A strategy
      of "no prophylaxis" was the least expensive one at 1 and 5 years after surgery.
      Compared to this approach, AZA/6-MP had the most favorable incremental cost
      effectiveness ratio (ICER) ($299,188/QALY gained), and yielded the highest net
      health benefits of the medication strategies at 1 year. Sensitivity analysis
      determined that the ICER of AZA/6-MP was preferable to mesalamine up to a
      recurrence rate of 52%, but mesalamine dominated at higher rates. In the 5-year
      exploratory analysis, mesalamine had the most favorable ICER over 5 years
      ($244,177/QALY gained). CONCLUSIONS: Compared to no prophylactic treatment, AZA/6
      MP has the most favorable ICER in the prevention of clinical recurrence of
      postoperative CD up to 1 year. At 5 years, mesalamine had the most favorable ICER
      in this model.

PMID- 21905178
TI  - Porous indium-organic frameworks and systematization of structural building
      blocks.

PMID- 21905179
TI  - Observing the hierarchical self-assembly and architectural bistability of hybrid
      molecular metal oxides using ion-mobility mass spectrometry.

PMID- 21905181
TI  - Highly efficient amide synthesis from alcohols and amines by virtue of a water
      soluble gold/DNA catalyst.

PMID- 21905180
TI  - Combinatorial catalysis employing a visible enzymatic beacon in real time:
      synthetically versatile (pseudo)halometalation/carbocyclizations.

PMID- 21905182
TI  - Tuning DNA stability to achieve turnover in template for an enzymatic ligation
      reaction.

PMID- 21905183
TI  - Palladium-catalyzed aryl iodide carbonylation as a route to imidazoline
      synthesis: design of a five-component coupling reaction.

PMID- 21905184
TI  - Porous and dense magnesium borohydride frameworks: synthesis, stability, and
      reversible absorption of guest species.

PMID- 21905185
TI  - Development of highly potent inhibitors of the Ras-targeting human acyl protein
      thioesterases based on substrate similarity design.
AB  - A matter of common sense: a common recognition motif consisting of a negatively
      charged group five to six bonds away (red) from the (thio)ester functionality
      (green) and a positively charged tail group ten to twelve bonds away (blue) was
      identified in two native acyl protein thioesterase 1 (APT1) substrates. This
      similarity led to the design of potent inhibitors of the Ras-depalmitoylating
      enzyme APT1.

PMID- 21905186
TI  - Identification of acyl protein thioesterases 1 and 2 as the cellular targets of
      the Ras-signaling modulators palmostatin B and M.
AB  - Finding the target: activity-based proteomic profiling probes based on the
      depalmitoylation inhibitors palmostatin B and M have been synthesized and were
      found to target acyl protein thioesterase 1 (APT1) and 2 (APT2) in cells.

PMID- 21905187
TI  - Control of circadian phase by an artificial zinc finger transcription regulator.

PMID- 21905189
TI  - High-performance silicon nanowire array photoelectrochemical solar cells through
      surface passivation and modification.
AB  - Nanowire solar cells: Pt nanoparticle (PtNP) decorated C/Si core/shell nanowire
      photoelectrochemical solar cells show high conversion efficiency of 10.86 % and
      excellent stability in aggressive electrolytes under 1-sun AM 1.5 G illumination.
      Superior device performance is achieved by improved surface passivation of the
      nanowires by carbon coating and enhanced interfacial charge transfer by PtNPs.

PMID- 21905190
TI  - Low-pressure hydrogenation of carbon dioxide catalyzed by an iron pincer complex
      exhibiting noble metal activity.
AB  - A highly active iron catalyst for the hydrogenation of carbon dioxide and
      bicarbonates works under remarkably low pressures and achieves activities similar
      to some of the best noble metal catalysts. A mechanism is proposed involving the
      direct attack of an iron trans-dihydride on carbon dioxide, followed by ligand
      exchange and dihydrogen coordination.

PMID- 21905191
TI  - A sphere-in-sphere complex by orthogonal self-assembly.

PMID- 21905192
TI  - Switchable catalysis with a light-responsive cavitand.

PMID- 21905193
TI  - Delineation of the core aggregation sequences of TDP-43 C-terminal fragment.
AB  - Ubiquitinated cytoplasmic inclusions of TDP-43 and its C-terminal cleavage
      products are the pathological hallmarks of amyotrophic lateral sclerosis and
      frontotemporal lobar degeneration with ubiquitinated inclusions. The C-terminal
      fragments (CTFs) of TDP-43 are increasingly considered to play an important role
      in its aggregation and in disease. Here, we employed a set of synthetic peptides
      spanning the length of the TDP-43 CTF (220-414) in order to find out its core
      aggregation domains. Two regions, one in the RRM-2 domain (246-255) and the other
      in the C-terminal domain (311-320) of TDP-43, stand out as highly aggregation
      prone. Studies done on recombinant purified TDP-43 CTF and its three mutants, in
      which these sequences were deleted individually and together, suggested that the
      311-320 region has a more crucial role to play than the 246-255 in its
      aggregation. The study helps in defining specific peptide sequences that might
      form the core of TDP-43 aggregation. Identification of these sequences could help
      in designing peptide based inhibitors of TDP-43 aggregation.

PMID- 21905194
TI  - Identification of anchor points for chemical modification of a small cysteine
      rich protein by using a cysteine scan.
AB  - Chemical modifications of proteins are increasingly important in the development
      of protein drugs with fine-tuned properties. Regioselective modification, such as
      the chemoselective alkylation of an unpaired cysteine residue, is a prerequisite
      for obtaining homogenous protein products. The introduction of an unpaired Cys
      into the Cys-rich protein, insulin, was investigated by using a Cys scan. This
      was challenging as the introduced Cys could interfere with insulin's three
      existing disulfide bonds. However, eight insulin precursors were expressed in
      Saccharomyces cerevisiae with good yields. Although extensive post-translational
      modifications of the unpaired Cys were observed, the majority could be removed by
      selective reduction. An example Cys(7)  insulin analogue was modified with a
      PEGylated maleimide moiety. The new variant was active in in vitro and in vivo
      models. Our results show that even small Cys-rich proteins can be expressed with
      additional unpaired Cys in meaningful yields and further chemically modified,
      while maintaining their biological activity.

PMID- 21905195
TI  - Biophysical investigations of GBV-C E1 peptides as potential inhibitors of HIV-1
      fusion peptide.
AB  - Five peptide sequences corresponding to the E1 protein of GBV-C
      [NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10),
      QAGLAVRPGKSAAQLVGE (P18), and AQLVGELGSLYGPLSVSA (P22)] were synthesized because
      they were capable of interfering with the HIV-1 fusion peptide (HIV-1 FP)-vesicle
      interaction. In this work the interaction of these peptides with the HIV-1 FP, as
      well as with membrane models, was analyzed to corroborate their inhibition
      ability and to understand if the interaction with the fusion peptide takes place
      in solution or at the membrane level. Several studies were carried out on
      aggregation and membrane fusion, surface Plasmon resonance, and conformational
      analysis by circular dichroism. Moreover, in vitro toxicity assays, including
      cytotoxicity studies in 3T3 fibroblasts and hemolysis assays in human red blood
      cells, were performed to evaluate if these peptides could be potentially used in
      anti-HIV-1 therapy. Results show that P10 is not capable of inhibiting membrane
      fusion caused by HIV-1 and it aggregates liposomes and fuses membranes, thus we
      decided to discard it for futures studies. P18 and P22 do not inhibit membrane
      fusion, but they inhibit the ability of HIV-1 FP to form pores in bilayers, thus
      we have not discarded them yet. P7 and P8 were selected as the best candidates
      for future studies because they are capable of inhibiting membrane fusion and the
      interaction of HIV-1 FP with bilayers. Therefore, these peptides could be
      potentially used in future anti-HIV-1 research.

PMID- 21905196
TI  - Ultrafast dynamics of UV-excited imidazole.
AB  - The ultrafast dynamics of UV-excited imidazole in the gas phase is investigated
      by theoretical nonadiabatic dynamics simulations and experimental time-resolved
      photoelectron spectroscopy. The results show that different electronic excited
      state relaxation mechanisms occur, depending on the pump wavelength. When
      imidazole is excited at 239.6 nm, deactivation through the NH-dissociation
      conical intersection is observed on the sub-50 fs timescale. After 200.8 nm
      excitation, competition between NH-dissociation and NH-puckering conical
      intersections is observed. The NH-dissociation to NH-puckering branching ratio is
      predicted to be 21:4, and the total relaxation time is elongated by a factor of
      eight. A procedure for simulation of photoelectron spectra based on dynamics
      results is developed and employed to assign different features in the
      experimental spectra.

PMID- 21905197
TI  - Memoranda: History of the teaching of biochemistry in Mexico.

PMID- 21905198
TI  - Early endocrine and molecular changes in metabolic syndrome models.
AB  - The twenty-first century arrived in the middle of a global epidemic of metabolic
      syndrome (MS) and type 2 diabetes mellitus (DM2). It is generally accepted that
      an excess of nutrients linked to a low physical activity triggers the problem.
      However, the molecular features that interact to develop the MS are not clear. In
      an effort to understand and control them, they have been extensively studied, but
      this goal has not been achieved yet. Nonhuman animal models have been used to
      explore diet and genetic factors in which experimental conditions are controlled.
      For example, only one factor in the diet, such as fats or carbohydrates can be
      modified to better understand a single change that would be impossible in humans.
      Most of the studies have been done in rodents. However, it is difficult to
      directly compare them, because experiments are different in more than one
      variable; genetic strains, amount, and the type of fat used in the diet and sex.
      Thus, the only possible criteria of comparison are the relevance of the observed
      changes. We review different animal models and add some original observations on
      short-term changes in metabolism and beta cells in our own model of adult Wistar
      rats that are not especially prone to get fat or develop DM2, treated with 20%
      sucrose in drinking water. One early change observed in pancreatic beta cells is
      the increase in GLUT2 expression that is located to the membrane of the cells.
      This change could partially explain the presence of insulin hypersecretion and
      hyperinsulinemia in these rats. Understanding early changes that lead to MS and
      in time to pancreatic islet exhaustion is an important biomedical problem that
      may contribute to learn how to prevent or even reverse MS, before developing DM2.

PMID- 21905199
TI  - Aluminum stress and its role in the phospholipid signaling pathway in plants and
      possible biotechnological applications.
AB  - An early response of plants to environmental signals or abiotic stress suggests
      that the phospholipid signaling pathway plays a pivotal role in these mechanisms.
      The phospholipid signaling cascade is one of the main systems of cellular
      transduction and is related to other signal transduction mechanisms. These other
      mechanisms include the generation of second messengers and their interactions
      with various proteins, such as ion channels. This phospholipid signaling cascade
      is activated by changes in the environment, such as phosphate starvation, water,
      metals, saline stres, and plant-pathogen interactions. One important factor that
      impacts agricultural crops is metal-induced stress. Because aluminum has been
      considered to be a major toxic factor for agriculture conducted in acidic soils,
      many researchers have focused on understanding the mechanisms of aluminum
      toxicity in plants. We have contributed the last fifteen years in this field by
      studying the effects of aluminum on phospholipid signaling in coffee, one of the
      Mexico's primary crops. We have focused our research on aluminum toxicity
      mechanisms in Coffea arabica suspension cells as a model for developing future
      contributions to the biotechnological transformation of coffee crops such that
      they can be made resistant to aluminum toxicity. We conclude that aluminum is
      able to not only generate a signal cascade in plants but also modulate other
      signal cascades generated by other types of stress in plants. The aim of this
      review is to discuss possible involvement of the phospholipid signaling pathway
      in the aluminum toxicity response of plant cells.

PMID- 21905200
TI  - CD43 regulates the threshold for T cell activation by targeting Cbl functions.
AB  - T cell (TC) activation requires the coordinated signaling of the T cell receptor
      (TCR) and coreceptor molecules, allowing TCs to respond to lower degrees of TCR
      occupancy. Coreceptor molecules set the threshold for TC activation by
      controlling different regulatory signaling loops. The Cbl family members prevent
      undesired activation of T cells by regulating TCR signals. In this report, we
      show that TC prestimulation by the CD43 coreceptor molecule before TCR engagement
      inhibits TCR-dependent c-Cbl tyrosine phosphorylation, c-Cbl interaction with the
      adapter molecule Crk-L and promotes Cbl-b degradation in a PKCtheta-dependent
      manner. Consequently, the prolonged tyrosine phosphorylation and delayed
      degradation of ZAP-70 and of the zeta chain lead to enhanced mitogen-activated
      protein kinase activation and robust TC response. These data indicates that CD43
      mediated signals lower the threshold for TC activation by restricting the c-Cbl
      and Cbl-b inhibitory effects on TCR signaling. In addition to the strength and
      duration of intracellular signals, our data underscore temporality with which
      certain molecules are engaged as yet another mechanism to fine tune TC signal
      quality, and ultimately immune function.

PMID- 21905201
TI  - Signaling through Toll-like receptor 4 and mast cell-dependent innate immunity
      responses.
AB  - Signal transduction through Toll-like receptors (TLRs) has been one of the main
      topics in immunology research in recent years. Because of their signaling
      particularities based on the homotypic recognition of protein domains in multiple
      adaptors and selective activation of protein kinases, TLRs have become a paradigm
      to study ligand recognition coupled to dynamic and highly specific
      transcriptional and secretory responses in immune cells. Particularly,
      deleterious effects of Gram-negative bacteria-associated immune reactions has
      promoted intense research in the field, leading to the description of a number of
      canonical molecules connecting lipopolysaccharide-induced TLR4 activation with
      NFkappaB-dependent transcription. However, the diversity of immune cell
      phenotypes and the activity of distinct immune receptors in the same cell,
      strongly suggest that a number of elements in TLR4 signaling cascade, such as
      novel coreceptors, tyrosine kinases, and molecules regulating the secretion of
      preformed mediators remain to be described. Recent investigations have placed the
      mast cells, widely known by their role on allergic responses, as important
      effectors of innate immunity reactions against Gram-negative bacteria. Their
      remarkable capacity of cytokine storage, synthesis and release, and the large
      number of inflammatory reactions controlled by their activation, suggest the
      existence of new modulators of TLR4 signaling in this particular cell type.

PMID- 21905202
TI  - mTORC1- and mTORC2-interacting proteins keep their multifunctional partners
      focused.
AB  - The mammalian target of rapamycin, best known as mTOR, is a phylogenetically
      conserved serine/threonine kinase that controls life-defining cellular processes
      such as growth, metabolism, survival, and migration under the influence of
      multiple interacting proteins. Historically, the cellular activities blocked by
      rapamycin in mammalian cells were considered the only events controlled by mTOR.
      However, this paradigm changed with the discovery of two signaling complexes
      differentially sensitive to rapamycin, whose catalytic component is mTOR. The one
      sensitive to rapamycin, known as mTORC1, promotes protein synthesis in response
      to growth factors and nutrients via the phosphorylation of p70S6K and 4EBP1;
      while the other, known as mTORC2, promotes cell migration and survival via the
      activation of Rho GTPases and the phosphorylation of AKT, respectively. Although
      mTORC2 kinase activity is not inhibited by rapamycin, hours of incubation with
      this antibiotic can impede the assembly of this signaling complex. The direct
      mechanism by which mTORC2 leads to cell migration depends on its interaction with
      P-Rex1, a Rac-specific guanine nucleotide exchange factor, while additional
      indirect pathways involve the intervention of PKC or AKT, multifunctional
      ubiquitous serine/threonine kinases that activate effectors of cell migration
      upon being phosphorylated by mTORC2 in response to chemotactic signals. These
      mTORC2 effectors are altered in metastatic cancer. Numerous clinical trials are
      testing mTOR inhibitors as potential antineoplasic drugs. Here, we briefly review
      the actions of mTOR with emphasis on the controlling role of mTORC1 and mTORC2
      interacting proteins and highlight the mechanisms linked to cell migration.

PMID- 21905203
TI  - Protein kinase C in Wnt signaling: implications in cancer initiation and
      progression.
AB  - Although it is well known that Wnt and protein kinase C (PKC) signaling pathways
      are both involved in carcinogenesis and tumor progression, their synergistic
      contribution to these processes or the crosstalk between them has just recently
      been approached. The Wnt and PKC signaling are involved in many cellular
      functions including proliferation, differentiation, survival, apoptosis,
      cytoskeletal remodeling, and cell motility. Canonical Wnt signaling has been well
      characterized as one of the most important contributors to tumorigenesis, and it
      has been implicated in many types of solid tumors. PKC is one of the key targets
      of noncanonical Wnt signaling, particularly in the Wnt/Ca(2+) pathway. Recently,
      data have implicated components of noncanonical Wnt/Ca(2+) and Wnt/planar cell
      polarity signaling in directly promoting the invasiveness and malignant
      progression of diverse forms of human cancer. But, unlike the canonical pathway,
      defining the roles of noncanonical Wnt signaling in human cancer is in its
      infancy. In this review, we provide a concise description of the current
      knowledge of the interaction between PKC and Wnt pathways and discuss the role of
      this crosstalk in cancer initiation and progression.

PMID- 21905204
TI  - Detection of hydrogen sulphide using cataluminescence sensors based on alkaline
      earth metal salts.
AB  - Detection of hydrogen sulphide (H(2)S) was conducted based on cataluminescence
      (CTL) sensors, using alkaline-earth metal carbonates as catalysts. Optimal
      working conditions, analytical characteristics and the response properties of the
      sensor were investigated. CTL intensity examination showed that sensors
      fabricated with CaCO(3), SrCO(3) or BaCO(3) could be used to detect H(2)S gas
      sensitively. The optimal sensing temperature was about 320  degrees C. Under the
      sensing conditions with temperature at ca. 320  degrees C and gas flow rate in
      the range 180-200 mL/min, the linear range of CTL intensity vs H(2)S
      concentration was 25-500 ppm, with a detection limit of 2 ppm. The response and
      recovery times of the sensor were within 5 and 25 min, respectively. Also, the
      sensor had the property of high selectivity to H(2)S with very weak or no obvious
      response to 14 other gases, such as NO(2), NH(3), hydrocarbons and alcohol.

PMID- 21905205
TI  - Total synthesis and functional analysis of non-ribosomal peptides.
AB  - Antillatoxin and polytheonamide B are cytotoxic non-ribosomal peptides, both
      isolated from marine sources. These molecules possess unique biological
      activities that relate to ion channel proteins. Antillatoxin binds and activates
      voltage-gated sodium channels, while polytheonamide mimics functions of an ion
      channel protein. The goal of this research program is to control the function and
      behavior of ion channels in a desired fashion by exploiting structural motifs of
      these natural products. In the opening phase of this program, we first developed
      general and efficient synthetic routes to antillatoxin and polytheonamide B. The
      strategies for the total syntheses were then applied to the preparation of
      structurally varied derivatives for studies of structure-function relationships,
      which resulted in deciphering important structural elements for the potent
      biological activities of these natural products.

PMID- 21905206
TI  - Cell labeling approaches for fluorescence-based in vivo flow cytometry.
AB  - We provide an overview of the methods used to label circulating cells for
      fluorescence detection by in vivo flow cytometry. These methods are useful for
      cell tracking in small animals without the need to draw blood samples and are
      particularly useful for the detection of circulating cancer cells and
      quantification of circulating immune cells.

PMID- 21905208
TI  - In vivo plant flow cytometry: a first proof-of-concept.
AB  - In vivo flow cytometry has facilitated advances in the ultrasensitive detection
      of tumor cells, bacteria, nanoparticles, dyes, and other normal and abnormal
      objects directly in blood and lymph circulatory systems. Here, we propose in vivo
      plant flow cytometry for the real-time noninvasive study of nanomaterial
      transport in xylem and phloem plant vascular systems. As a proof of this concept,
      we demonstrate in vivo real-time photoacoustic monitoring of quantum dot-carbon
      nanotube conjugates uptake by roots and spreading through stem to leaves in a
      tomato plant. In addition, in vivo scanning cytometry using multimodal
      photoacoustic, photothermal, and fluorescent detection schematics provided
      multiplex detection and identification of nanoparticles accumulated in plant
      leaves in the presence of intensive absorption, scattering, and autofluorescent
      backgrounds. The use of a portable fiber-based photoacoustic flow cytometer for
      studies of plant vasculature was demonstrated. These integrated cytometry
      modalities using both endogenous and exogenous contrast agents have a potential
      to open new avenues of in vivo study of the nutrients, products of photosynthesis
      and metabolism, nanoparticles, infectious agents, and other objects transported
      through plant vasculature.

PMID- 21905209
TI  - P-glycoprotein activity in human Caucasian male lymphocytes does not follow its
      increased expression during aging.
AB  - P-glycoprotein (P-gp) is a transmembrane protein that mediates the efflux of
      innumerous structurally unrelated compounds. It was initially found over
      expressed in tumor cells, associated to a multidrug resistance phenotype (MDR).
      Then, P-gp was found constitutively expressed in excretory cells/tissues and in
      circulating cells, such as lymphocytes. Considering the importance of this
      transporter in the establishment of therapeutic protocols and the existence of
      contradictory results, this study aimed at evaluating the influence of aging in
      the expression and function of P-gp in human lymphocytes, comparing two different
      methodologies to assess both parameters. P-gp activity and expression were
      evaluated in lymphocytes isolated from whole blood samples of 65 healthy
      caucasian male donors, divided into two groups according to age (group 1: under
      30-years old; group 2: above 60-years old). P-gp expression was assessed using
      the anti-P-gp monoclonal antibody, UIC2, in the presence and in absence of
      vinblastine (Vbl). P-gp activity was evaluated measuring the efflux rate of the
      fluorescent P-gp substrate rhodamine 123 (Rho 123) and also using UIC2 shift
      assay. Flow cytometric analysis was performed to assess all the proceedings.
      Furthermore, P-gp expression and each of the P-gp activity determination methods
      were compared, through correlation analysis and linear regression models. We
      observed a significant age-dependent increase in mean P-gp expression (p =
      0.029), which was not reflected in the transporter's activity (p > 0.050).
      Statistical analysis allowed selection of UIC2 shift assay over Rho 123 efflux
      assay as a more selective method to assess P-gp activity. Despite the significant
      correlation between P-gp expression and P-gp activity found in lymphocytes
      (Gp1(group 1)-r = 0.609, p < 0.001; Gp2-r = 0.461, p = 0.012), using UIC2 shift
      assay, these data reinforce the need for P-gp activity assessment, rather than P
      gp expression determination alone, when starting new therapeutic regimens with P
      gp substrates, especially in men older than 60 years of age.

PMID- 21905207
TI  - In vivo multispectral photoacoustic and photothermal flow cytometry with
      multicolor dyes: a potential for real-time assessment of circulation, dye-cell
      interaction, and blood volume.
AB  - Recently, photoacoustic (PA) flow cytometry (PAFC) has been developed for in vivo
      detection of circulating tumor cells and bacteria targeted by nanoparticles.
      Here, we propose multispectral PAFC with multiple dyes having distinctive
      absorption spectra as multicolor PA contrast agents. As a first step of our proof
      of-concept, we characterized high-speed PAFC capability to monitor the clearance
      of three dyes (Indocyanine Green [ICG], Methylene Blue [MB], and Trypan Blue
      [TB]) in an animal model in vivo and in real time. We observed strong dynamic PA
      signal fluctuations, which can be associated with interactions of dyes with
      circulating blood cells and plasma proteins. PAFC demonstrated enumeration of
      circulating red and white blood cells labeled with ICG and MB, respectively, and
      detection of rare dead cells uptaking TB directly in bloodstream. The possibility
      for accurate measurements of various dye concentrations including Crystal Violet
      and Brilliant Green were verified in vitro using complementary to PAFC
      photothermal (PT) technique and spectrophotometry under batch and flow
      conditions. We further analyze the potential of integrated PAFC/PT spectroscopy
      with multiple dyes for rapid and accurate measurements of circulating blood
      volume without a priori information on hemoglobin content, which is impossible
      with existing optical techniques. This is important in many medical conditions
      including surgery and trauma with extensive blood loss, rapid fluid
      administration, and transfusion of red blood cells. The potential for developing
      a robust clinical PAFC prototype that is safe for human, and its applications for
      studying the liver function are further highlighted.

PMID- 21905212
TI  - Recent advances in dynamic intravital multi-photon microscopy.
AB  - Standard multiphoton laser scanning microscopy (MPLSM) has revolutionized our
      view of physiologic and pathologic processes in living organisms by enlightening
      different aspects of cellular choreography in immune responses, that is, cellular
      motility and co-localization. To understand cellular communication on a molecular
      level, novel transgenic reporter mice have been generated. In parallel, MPLSM
      systems have been developed, which make it possible for this technique to be more
      widely used to address crucial immunological questions. Here, we review the
      latest progress concerning transgenic mouse technology and multiphoton imaging
      capacities and discuss further developments which will enable us to visualize all
      around monitoring and quantification of cellular function at a molecular level
      directly in vivo.

PMID- 21905211
TI  - Development of high-throughput methods to quantify cysts of Toxoplasma gondii.
AB  - Toxplasma is a protozoan parasite, which forms persistent cysts in tissues of
      chronically infected animals and humans. Cysts can reactivate leading to severe
      pathologies. They also contribute to the transmission of Toxoplasma infection in
      humans by ingestion of undercooked meat. Classically, the quantification of cyst
      burden in tissues uses microscopy methods, which are laborious and time
      consuming. Here, we have developed automated protocols to quantify cysts, based
      on flow cytometry or high-throughput microscopy. Brains of rodents infected with
      cysts of Prugniaud strain were incubated with the FITC-Dolichos biflorus lectin
      and analyzed by flow cytometry and high-throughput epifluorescence microscopy.
      The comparison of cyst counts by manual epifluorescence microscopy to flow
      cytometry or to high-throughput epifluorescence microscopy revealed a good
      correlation (r = 0.934, r = 0.993, P < 0.001 respectively). High-throughput
      epifluorescence microscopy was found to be more specific and sensitive than flow
      cytometry and easier to use for large series of samples. This reliable and easy
      protocol allow the specific detection of Toxoplasma cysts in brain, even at low
      concentrations; it could be a new way to detect them in water and in contaminate
      food.

PMID- 21905210
TI  - Induction of DNA damage signaling by oxidative stress in relation to DNA
      replication as detected using "click chemistry".
AB  - Induction of DNA damage by oxidants such as H(2) O(2) activates the complex
      network of DNA damage response (DDR) pathways present in cells to initiate DNA
      repair, halt cell cycle progression, and prepare an apoptotic reaction. We have
      previously reported that activation of Ataxia Telangiectasia Mutated protein
      kinase (ATM) and induction of gammaH2AX are among the early events of the DDR
      induced by exposure of cells to H(2) O(2) , and in human pulmonary carcinoma A549
      cells, both events were expressed predominantly during S-phase. This study was
      designed to further explore a correlation between these events and DNA
      replication. Toward this end, we utilized 5-ethynyl-2'deoxyuridine (EdU) and the
      "click chemistry" approach to label DNA during replication, followed by exposure
      of A549 cells to H(2) O(2) . Multiparameter laser scanning cytometric analysis of
      these cells made it possible to identify DNA replicating cells and directly
      correlate H(2) O(2) -induced ATM activation and induction of gammaH2AX with DNA
      replication on a cell by cell basis. After pulse-labeling with EdU and exposure
      to H(2) O(2) , confocal microscopy was also used to examine the localization of
      DNA replication sites ("replication factories") versus the H2AX phosphorylation
      sites (gammaH2AX foci) in nuclear chromatin in an attempt to observe the absence
      or presence of colocalization. The data indicate a close association between DNA
      replication and H2AX phosphorylation in A549 cells, suggesting that these DNA
      damage response events may be triggered by stalled replication forks and perhaps
      also by induction of DNA double-strand breaks at the primary DNA lesions induced
      by H(2) O(2) .

PMID- 21905213
TI  - Contamination of the cell sorter fluidics system with the water-borne bacterium
      Burkholderia cepacia.

PMID- 21905214
TI  - In vitro evaluation of an injectable chitosan gel for sustained local delivery of
      BMP-2 for osteoblastic differentiation.
AB  - We investigated the effect of sustained release of bone morphogenetic protein-2
      (BMP-2) from an injectable chitosan gel on osteoblastic differentiation in vitro.
      We first characterized the release profile of BMP-2 from the gels, and then
      examined the cellular responses of preosteoblast mouse stromal cells (W-20-17)
      and human embryonic palatal mesenchymal (HEPM) cells to BMP-2. The release
      profiles of different concentrations of BMP-2 exhibited sustained releases (41%
      for 2 ng/mL and 48% for 20 ng/mL, respectively) from the chitosan gels over a
      three-week period. Both cell types cultured in the chitosan gels were viable and
      significantly proliferated for 3 days (p < 0.05). Chitosan gels loaded with BMP-2
      enhanced ALP activity of W-20-17 by 3.6-fold, and increased calcium mineral
      deposition of HEPM by 2.8-fold at 14 days of incubation, compared to control
      groups initially containing the same amount of BMP-2. In addition, schitosan gels
      loaded with BMP-2 exhibited significantly greater osteocalcin synthesis of W-20
      17 at seven days, and of HEPM at both 7 and 14 days compared with the control
      groups (p<0.05). This study suggests that the enhanced effects of BMP-2 released
      from chitosan gels on cell differentiation and mineralization are species and
      cell type dependent.

PMID- 21905215
TI  - A simplified in vivo approach for evaluating the bioabsorbable behavior of
      candidate stent materials.
AB  - Metal stents are commonly used to revascularize occluded arteries. A
      bioabsorbable metal stent that harmlessly erodes away over time may minimize the
      normal chronic risks associated with permanent implants. However, there is no
      simple, low-cost method of introducing candidate materials into the arterial
      environment. Here, we developed a novel experimental model where a biomaterial
      wire is implanted into a rat artery lumen (simulating bioabsorbable stent blood
      contact) or artery wall (simulating bioabsorbable stent matrix contact). We use
      this model to clarify the corrosion mechanism of iron (>=99.5 wt %), which is a
      candidate bioabsorbable stent material due to its biocompatibility and mechanical
      strength. We found that iron wire encapsulation within the arterial wall
      extracellular matrix resulted in substantial biocorrosion by 22 days, with a
      voluminous corrosion product retained within the vessel wall at 9 months. In
      contrast, the blood-contacting luminal implant experienced minimal biocorrosion
      at 9 months. The importance of arterial blood versus arterial wall contact for
      regulating biocorrosion was confirmed with magnesium wires. We found that
      magnesium was highly corroded when placed in the arterial wall but was not
      corroded when exposed to blood in the arterial lumen for 3 weeks. The results
      demonstrate the capability of the vascular implantation model to conduct rapid in
      vivo assessments of vascular biomaterial corrosion behavior and to predict long
      term biocorrosion behavior from material analyses. The results also highlight the
      critical role of the arterial environment (blood vs. matrix contact) in directing
      the corrosion behavior of biodegradable metals.

PMID- 21905216
TI  - Optimizing conditions for the extraction of catechins from green tea using hot
      water.
AB  - Six different factors involved in the extraction of catechins from green tea
      using water were examined for their impact on the yield of catechins and on the
      efficiency of water use. The best temperature and time combination for catechin
      extraction was at 80 degrees C for 30 min. The yield of catechins was also
      optimal with a tea particle size of 1 mm, a brewing solution pH <6 and a tea-to
      water ratio at 50:1 (mL/g). In terms of efficient use of water in a single
      extraction, a water-to-tea ratio of 20:1 (mL/g) gave the best results; 2.5 times
      less water was used per gram of green tea. At the water-to-tea ratio of 20:1
      mL/g, the highest yield of catechins per gram of green tea was achieved by
      extracting the same sample of green tea twice. However, for the most efficient
      use of water, the best extraction was found to be once at a water-to-tea ratio of
      12:1 (mL/g) and once at a water-to-tea ratio of 8:1 (mL/g). Therefore, all six of
      the factors investigated had an impact on the yield of catechins extracted from
      green tea using water and two had an impact on the efficiency of water use.

PMID- 21905218
TI  - Development and validation of a chiral capillary electrophoresis method for assay
      and enantiomeric purity control of pramipexole.
AB  - A rapid method for the enantioseparation of pramipexole and its R-enantiomer has
      been developed by capillary electrophoresis. The influence of chemical and
      instrumental parameters was investigated including the type and concentration of
      chiral selectors, buffer composition and pH, co-ions, applied voltage, capillary
      length and temperature. Optimal separation conditions were obtained using a 50 mM
      phosphate buffer (pH 2.8) containing 25 mM carboxymethyl-beta-cyclodextrin on a
      fused-silica capillary. Online UV detection was performed at 262 nm. A voltage of
      25 kV was applied, and the capillary temperature was kept at 25 degrees C.
      Hydrodynamic injection was performed at 3.45 kPa for 5.0 s. The separation of
      enantiomers was achieved in <6.5 min. The method was further validated in terms
      of stability of solutions, selectivity, linearity (both pramipexole and R
      enantiomer, R(2) >0.995), LOD and LOQ (0.91 and 2.94 MUg/mL, respectively),
      repeatability (RSD<1.5%) and accuracy (pramipexole, 100.4%; R-enantiomer,
      100.5%). The proposed method was then applied to two kinds of pramipexole
      dihydrochloride monohydrate commercially available tablets, immediate release
      tablets (1.50 and 0.125 mg) and sustained release tablets (0.52 mg), to quantify
      the main component in the tablets. The amount of distomer could be quantified in
      bulk sample materials.

PMID- 21905217
TI  - Quantitative analysis and chromatographic fingerprinting of the semen zizyphi
      spinosae by ultra-high-performance liquid chromatography coupled with diode-array
      detector.
AB  - A simple and sensitive method was developed and validated for fingerprint
      analysis of semen zizyphi spinosae (SZS) and simultaneous determination of six
      flavonoids in SZS by ultra-high-performance liquid chromatography coupled to
      diode-array detector (DAD). The analysis was performed on an Agilent ZORBAX
      Eclipse Plus C18 RRHD column. The column was maintained at 40 degrees C and the
      eluents were monitored with DAD at 270 nm. A gradient elution of acetonitrile and
      water containing 20 mM sodium dihydrogen phosphate was used. The solvent flow
      rate was 0.4 mL/min. The method was validated. Standard calibration curves showed
      good linear behaviors (r=1.000) in the range of 0.33-201.00 MUg/mL. Acceptable
      intra-day precision (RSD<1.9%), inter-day precision (RSD<4.0%), repeatability
      (RSD<4.1%) and recovery in the range of 97.4-104% were obtained. The validated
      method was successfully applied to obtain the chromatographic fingerprints and
      the contents of six flavonoids in 23 samples of SZS. The principal component
      analysis (PCA) had been applied for the chromatographic fingerprint analysis and
      quantitative analysis of six flavonoids to classify and discriminate the 23
      samples of SZS. These results demonstrated that the method was very suitable in
      the analysis and quality control of SZS.

PMID- 21905219
TI  - Gel-free proteomic identification of the Bacillus subtilis insoluble spore coat
      protein fraction.
AB  - Species from the genus Bacillus have the ability to form endospores, dormant
      cellular forms that are able to survive heat and acid preservation techniques
      commonly used in the food industry. Resistance characteristics of spores towards
      various environmental stresses are in part attributed to their coat proteins.
      Previously, 70 proteins have been assigned to the spore coat of Bacillus subtilis
      using SDS-PAGE, 2-DE gel approaches, protein localization studies and genome-wide
      transcriptome studies. Here, we present a "gel-free" protocol that is capable of
      comprehensive B. subtilis spore coat protein extraction and addresses the
      insoluble coat fraction. Using LC-MS/MS we identified 55 proteins from the
      insoluble B. subtilis spore coat protein fraction, of which 21 are putative novel
      spore coat proteins not assigned to the spore coat until now. Identification of
      spore coat proteins from a B. subtilis food-spoilage isolate corroborated a
      generic and "applied" use of our protocol. To develop specific and sensitive
      spore detection and/or purification systems from food stuff or patient material,
      suitable protein targets can be derived from our proteomic approach. Finally, the
      protocol can be extended to study cross-linking among the spore coat proteins as
      well as for their quantification.

PMID- 21905220
TI  - Increased expression of peroxiredoxin 1 and identification of a novel lipid
      metabolizing enzyme in the early phase of liver ischemia reperfusion injury.
AB  - Warm ischemia reperfusion (IR) injury of the liver is associated with changes in
      the expression and/or post-translational modification of numerous proteins. Only
      a few of these have been identified. We used 2-D DIGE to identify cytosolic
      proteins altered in the early stage of IR in an established rat model of
      segmental hepatic ischemia. Proteins in 18 abundant spots altered by IR were
      identified by LC-MS/MS and Western blot. Many identified proteins were enzymes
      involved in glucose and lipid metabolism. Isoamyl acetate-hydrolysing esterase 1
      homolog, not previously characterized in liver, was also identified. A threefold
      increase in peroxiredoxin 1 (Prx1) and its oxidized forms was observed as was an
      increase in Prx1 mRNA. Peroxiredoxins and their overoxidation have previously
      been associated with IR. In contrast to other studies, we did not detect typical
      overoxidation of Prx1 on the peroxidatic cysteine (Cys(52)). Instead, we
      identified novel overoxidation of the resolving cysteine (Cys(173)) residue by LC
      MS/MS. Our results show that a rapid increase in Prx1 expression is associated
      with the early phase of IR of the liver, likely contributing to mechanisms that
      protect the liver against IR damage. Additionally, we have revealed a potential
      role in liver for a novel lipid-metabolizing enzyme.

PMID- 21905221
TI  - Coordination of carbon fixation and nitrogen metabolism in Salicornia europaea
      under salinity: Comparative proteomic analysis on chloroplast proteins.
AB  - Halophyte, like Salicornia europaea, could make full use of marginal saline land
      for carbon fixation. How the photosynthesis of S. europaea is regulated under
      high salinity implicates a significant aspect to exploit this pioneer plant in
      future. Measurement of photosynthesis parameters demonstrated the reduction of
      photosynthesis for the 0 and 800 mM NaCl treated plants are more likely due to
      non-stomatal limitation, which might be caused by changes in the enzymes
      associated with photosynthesis. Different salinity induced ultrastructure changes
      other than photosynthetic apparatus damage, suggesting the photosynthesis of S.
      europaea might be affected via biochemical regulation. Comparative proteomics
      analysis of chloroplast proteins by 2-D gel electrophoresis reproducibly detected
      90 differentially expressed proteins, among which 66 proteins were identified by
      nanoLC MS/MS. Further study of thylakoid membrane proteins by Blue-Native PAGE
      proved the increase in abundance of light reaction proteins under salinity.
      Analysis of gene expression patterns of 12 selected proteins provides evidence
      for the correlations between transcription and proteomics data. Based on our
      results, a putative model of photosynthesis regulatory network figured out proper
      coordination of carbon fixation and nitrogen metabolism in chloroplast of S.
      europaea under salinity, which provided subcellular level insight into salt
      tolerance mechanism in S. europaea.

PMID- 21905222
TI  - Preparation of magnetic core-mesoporous shell microspheres with C8-modified
      interior pore-walls and their application in selective enrichment and analysis of
      mouse brain peptidome.
AB  - In this paper, magnetic mesoporous silica microspheres with C8-modified interior
      pore-walls were prepared through a facile one-pot sol-gel coating strategy, and
      were successfully applied for selective enrichment of endogenous peptides in
      mouse brain for peptidome analysis. Through the one-pot sol-gel approach with
      surfactant (CTAB) as a template, tetraethyl orthosilicate (TEOS) and n
      ctyltriethoxysilane (C8TEOS) as the precursors, C8-modified magnetic mesoporous
      microspheres (C8-Fe(3)O(4)@mSiO(2)) consisting magnetic core and mesoporous
      silica shell with C8-groups exposed in the mesopore channels were synthesized.
      The obtained microspheres possess highly open mesopores of 3.4 nm, high surface
      area (162.5 m(2)/g), large pore volume (0.17 cm(3)/g), excellent magnetic
      responsivity (56.3 emu/g) and good dispersibility in aqueous solution. Based on
      the abundant surface silanol groups, functional C8 groups and the strong magnetic
      responsivity of the core-shell C8-Fe(3) O(4) @mSiO(2) microspheres, efficient and
      fast enrichment of peptides was achieved. Additionally, the C8-Fe(3)O(4)@mSiO(2)
      microspheres exhibit excellent performance in selective enrichment of endogenous
      peptides from complex samples that are consist of peptides, large proteins and
      other compounds, including human serum and mouse brain followed by automated nano
      LC-ESI-MS/MS analysis. These results indicate C8-Fe(3)O(4)@mSiO(2) microspheres
      would be a potential candidate for endogenous peptides enrichment and biomarkers
      discovery in peptidome analysis.

PMID- 21905223
TI  - Pulmonary pressure reduction attenuates expression of proteins identified by lung
      proteomic profiling in pulmonary hypertensive rats.
AB  - The present study was designed to analyze protein expression in lungs from
      pulmonary hypertensive rats in order to identify novel signaling pathways. This
      was achieved by proteomic studies in which proteins from lung homogenates from
      hypoxic were compared to normoxic rats. The expression of these proteins was then
      investigated in lungs from hypoxic rats treated with either an activator of
      soluble guanylyl cyclase, BAY 412272, or an inhibitor of phosphodiesterase type
      5, sildenafil. The proteomic study revealed an up-regulation of guanine
      nucleotide-binding protein beta, GST-omega-1, cathepsin D, chloride intracellular
      channel subunit 5, annexin A4, F-actin capping protein CapZ (CapZalpha), and the
      translation factor elongation factor 1 delta in lungs from chronic hypoxic rats
      with pulmonary hypertension. Immunohistochemistry revealed that CapZalpha,
      cathepsin D, and annexin A4 were expressed in the pulmonary vascular wall and
      immunoblotting showed these proteins correlated to alterations in
      muscularization. Both drugs inhibited hypoxia-induced increase in right
      ventricular systolic pressure and pulmonary arterial muscularization, and
      prevented most of the protein regulations observed after hypoxia. These findings
      suggest that pulmonary pressure is an important factor for initiating signaling
      pathways leading to protein expression and muscularization in the pulmonary
      vasculature.

PMID- 21905224
TI  - Emulsion electrospinning of a collagen-like protein/PLGA fibrous scaffold:
      empirical modeling and preliminary release assessment of encapsulated protein.
AB  - The effectiveness of a multifunctional scaffold produced by the electrospinning
      of emulsions composed of organic PLGA and aqueous collagen-like protein (denoted
      as Fol-8Col) solutions is demonstrated. The resultant Fol-8Col/PLGA fibrous
      scaffolds with homogeneous morphology have mean fiber diameters from 600 to 2,000
      nm. A uniform distribution of encapsulated Fol-8Col in the fibers is observed by
      fluorescence microscopy. TEM is used to clarify the representative core/sheath
      structure of emulsion electrospun Fol-8Col/PLGA fibers. Preliminary release
      assessment of encapsulated Fol-8Col shows results of sustained release for more
      than one month from the Fol-8Col/PLGA fibrous mats. The cytocompatibility of
      fibroblast cell line L929 with the fibrous composite seems promosing.

PMID- 21905225
TI  - TRAPping the cellular mechanisms of lupus.

PMID- 21905226
TI  - Enhancing the 3-hydroxyvalerate component in bioplastic PHBV production by
      Cupriavidus necator.
AB  - In the current context of global warming, the substitution of conventional
      plastics with bioplastics is a challenge. To take up this challenge, we must meet
      different technical and economic constraints. In the case of poly(3
      hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), the technical properties can be
      modulated by varying the 3-hydroxyvalerate content. 3-Hydroxyvalerate (3-HV)
      enhancement is an issue; therefore, simultaneous evaluation of several 3
      hydroxyvalerate-enhancing substrates through fractional factorial design of
      experiments is described. Eight substrates citric, valeric, propionic, and
      levulinic acids; propanol; pentanol; and sodium propionate were studied for 3-HV
      enhancement, and sodium glutamate was studied for biomass and
      polyhydroxyalkanoate (PHA) enhancement. The most efficient 3-hydroxyvalerate
      enhancing factors were levulinic acid, sodium propionate, and pentanol; however,
      pentanol, at a concentration of 1 g/L, had an extremely negative influence on
      biomass production and the PHA content of cells. The effect of the inoculum
      nutrient composition on the final 3-HVcontent was also evaluated. These results
      showed that the most efficient combination for the production of high 3-HVcontent
      in PHBV was primary inoculum growth on mineral medium followed by fermentation
      for 48 h with levulinic acid and sodium propionate (at 1 g/L) as the only carbon
      sources. This allowed us to produce PHBV with a 3-HVcontent of 80 mol % and
      overall volumetric and specific productivities of 2 mg/L/h and 3.9 mg/g(CDW) /h,
      respectively, with the addition of only 2 g/L of inducing substances.

PMID- 21905227
TI  - Simultaneous use of urea and potassium nitrate for Arthrospira (Spirulina)
      platensis cultivation.
AB  - Urea has been considered as a promising alternative nitrogen source for the
      cultivation of Arthrospira platensis if it is possible to avoid ammonia toxicity;
      however, this procedure can lead to periods of nitrogen shortage. This study
      shows that the addition of potassium nitrate, which acts as a nitrogen reservoir,
      to cultivations carried out with urea in a fed-batch process can increase the
      maximum cell concentration (X(m) ) and also cell productivity (P(X) ). Using
      response surface methodology, the model indicates that the estimated optimum X(m)
      can be achieved with 17.3 mM potassium nitrate and 8.9 mM urea. Under this
      condition an X(m)  of 6077 +/- 199 mg/L and a P(X)  of 341.5 +/- 19.1 mg L(-1)
      day(-1)  were obtained.

PMID- 21905228
TI  - Synthesis and antimalarial activities of a diverse set of triazole-containing
      furamidine analogues.
AB  - Four different series of triazole diamidines have been prepared by the Pinner
      method from the corresponding triazole dinitriles. Copper-catalyzed "click
      chemistry" was used for the synthesis of 1,4- and 4,5-substituted triazoles, aryl
      magnesium acetylide reagents for the 1,5-substituted triazoles, with a thermal
      dipolar addition reaction employed for the 2,4-substituted triazoles. In vitro
      antimalarial activity against two different PfCRT-modified parasite lines
      (Science 2002, 298, 210-213) of Plasmodium falciparum and inhibition of hemozoin
      formation were determined for each compound. Several diamidines with potent
      nanomolar antimalarial activities were identified, and selected molecules were
      resynthesized as their diamidoxime triazole prodrugs. One of these prodrugs,
      OB216, proved to be highly potent in vivo with an ED50 value of 5 mg kg(-1) (po)
      and an observed 100 % cure rate (CD100) of just 10 mg kg(-1) by oral (po)
      administration in mice infected with P. vinckei.

PMID- 21905229
TI  - Inhibition of aminoglycoside-deactivating enzymes APH(3')-IIIa and AAC(6')-Ii by
      amphiphilic paromomycin O2''-ether analogues.

PMID- 21905230
TI  - Preparation and function of poly(acrylic acid)s modified by supramolecular
      complex composed of porphinatoiron and a cyclodextrin dimer that bind diatomic
      molecules (O2 and CO) in aqueous solution.
AB  - Poly(acrylic acid) (PAA) is modified by 5-(4-beta-alanylaminophenyl)-10,15,20
      tris(4-sulfonatophenyl) porphinatoiron(III) to yield iron porphyrin-bearing PAAs
      (FeP(n)s) through a condensation reaction. FeP(n)s were further functionalized by
      Py3CD, which is a per-O-methylated beta-cyclodextrin (CD) dimer with a pyridine
      linker and includes the porphyrin pendants to form ferric hemoCD-P(n)s. Ferrous
      hemoCD-P(3), having three porphyrin chromophores in a polymer chain, is shown to
      bind molecular oxygen (P(1/2)=7.9+/-1.4 Torr) in aqueous solution at pH 7.0 and
      25  degrees C, affording oxy-hemoCD-P(3). Oxy-hemoCD-P(3) is biphasically
      autoxidized to ferric hemoCD-P(3), with 27% of the dioxygen adducts being rapidly
      oxidized. The rate of autoxidation of oxy-hemoCD-P(15), having 15 porphyrin
      chromophores in a polymer chain, was much faster than that of oxy-hemoCD-P(3),
      thus suggesting self-catalyzed autoxidation of oxy-hemoCD-P(n)s. Oxy-hemoCD-P(n)s
      are markedly stabilized by catalase, thereby indicating that hydrogen peroxide
      generated from oxy-hemoCD-P(n) accelerates the autoxidation. Most of the hemoCD
      P(3) molecules injected into the femoral vein of a rat remained in the body,
      though about 16% of the hemoCD-P(3) molecules were excreted in the urine as a
      carbon monoxide adduct.

PMID- 21905232
TI  - Bis(5,7-dimethyl-8-hydroxyquinolinato)platinum(II) complex for efficient organic
      heterojunction solar cells.
AB  - Organic photovoltaic (OPV) cells using metal(II) (Pt, Pd, Cu, and Ni) chelates of
      8-hydroxyquinoline (Hq) or 5,7-dimethyl-8-hydroxy-quinoline (HMe(2)q) as an
      electron donor were fabricated by vacuum deposition. The bis(5,7-dimethyl-8
      hydroxyquinolinato)platinum(II) [Pt(Me(2) q)(2)]-based OPVs showed the best
      performance with an open voltage (V(OC)) of 0.42 V, a short circuit current
      density (J(SC) ) of 14.8 mA cm(-2) , and a maximum power conversion efficiency
      (eta(P) ) of 2.4%. The X-ray single-crystal structures together with the grazing
      incidence X-ray diffraction (GIXRD) data of thin film samples reveal that the
      peripheral methyl substituent(s) and platinum(II) ion are essential for the high
      degree of film crystallinity resulting in improved performance of the as
      fabricated field-effect transistors (FETs) and OPV cells.

PMID- 21905231
TI  - Sulfated ligands for the copper(I)-catalyzed azide-alkyne cycloaddition.
AB  - The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), the prototypical
      reaction of click chemistry, is accelerated by tris(triazolylmethyl)amine-based
      ligands. Herein, we compare two new ligands in this family--3-[4-({bis[(1-tert
      butyl-1H-1,2,3-triazol-4-yl)methyl]amino}methyl)-1H-1,2,3-triazol-1-yl]propanol
      (BTTP) and the corresponding sulfated ligand 3-[4-({bis[(1-tert-butyl-1H-1,2,3
      triazol-4-yl)methyl]amino}methyl)-1H-1,2,3-triazol-1-yl]propyl hydrogen sulfate
      (BTTPS)--for three bioconjugation applications: 1) labeling of alkyne-tagged
      glycoproteins in crude cell lysates, 2) labeling of alkyne- or azide-tagged
      glycoproteins on the surface of live mammalian cells, and 3) labeling of azides
      in surface proteins of live Escherichia coli. Although BTTPS exhibits faster
      kinetics than BTTP in accelerating the CuAAC reaction in in vitro kinetic
      measurements, its labeling efficiency is slightly lower than BTTP in modifying
      biomolecules with a significant amount of negative charges due to electrostatic
      repulsion. Nevertheless, the negative charge conferred by the sulfate at
      physiological conditions significantly reduced the cellular internalization of
      the coordinated copper(I), thus making BTTPS-Cu(I) a better choice for live-cell
      labeling.

PMID- 21905234
TI  - Chemical Society of Vietnam.

PMID- 21905233
TI  - Thermoresponsive supramolecular dendronized polymers.
AB  - Combining the concepts of supramolecular polymers and dendronized polymers
      provides the opportunity to create bulky polymers with easy structural
      modification and tunable properties. In the present work, a novel class of side
      chain supramolecular dendronized polymethacrylates is prepared through the host
      guest interaction. The host is a linear polymethacrylate (as the backbone)
      attached in each repeat unit with a beta-cyclodextrin (beta-CD) moiety, and the
      guest is constituted with three-fold branched oligoethylene glycol (OEG)-based
      first-(G1) and second-generation (G2) dendrons with an adamantyl group core. The
      host and guest interaction in aqueous solution leads to the formation of the
      supramolecular polymers, which is supported with (1)H NMR spectroscopy and
      dynamic light scattering measurements. The supramolecular formation was also
      examined at different host/guest ratios. The water solubility of hosts and guests
      increases upon supramolecular formation. The supramolecular polymers show good
      solubility in water at room temperature, but exhibit thermoresponsive behavior at
      elevated temperatures. Their thermoresponsiveness is thus investigated with
      UV/Vis and (1)H NMR spectroscopy, and compared with their counterparts formed
      from individual beta-CD and the OEG dendritic guest. The effect of polymer
      concentration and molar ratio of host/guest was examined. It is found that the
      polar interior of the supramolecules contribute significantly to the thermally
      induced phase transitions for the G1 polymer, but this effect is negligible for
      the G2 polymer. Based on the temperature-varied proton NMR spectra, it is found
      that the host-guest complex starts to decompose during the aggregation process
      upon heating to its dehydration temperature, and this decomposition is enhanced
      with an increase of solution temperature.

PMID- 21905236
TI  - Comparative evaluation of the diagnostic performance of autofluorescence and
      diffuse reflectance in oral cancer detection: a clinical study.
AB  - Autofluorescence (AF) and diffuse reflectance (DR) spectroscopic techniques have
      shown good diagnostic accuracies for noninvasive detection of oral cavity cancer.
      In the present study, AF and DR spectra recorded in vivo from the same set of
      sites in 65 patients were analyzed using Principal component analysis (PCA) and
      linear discriminant analysis (LDA). The effectiveness of these two techniques was
      assessed by comparison with gold standard and their discrimination efficiency was
      determined from the area under the receiver operator characteristic (AUC-ROC)
      curve. Analysis using a DR technique shows a higher AUC-ROC of 0.991 as against
      0.987 for AF spectral data.

PMID- 21905237
TI  - Biotemplated materials for sustainable energy and environment: current status and
      challenges.
AB  - Materials science will play a key role in the further development of emerging
      solutions for the increasing problems of energy and environment. Materials found
      in nature have many inspiring structures, such as hierarchical organizations,
      periodic architectures, or nanostructures, that endow them with amazing
      functions, such as energy harvesting and conversion, antireflection, structural
      coloration, superhydrophobicity, and biological self-assembly. Biotemplating is
      an effective strategy to obtain morphology-controllable materials with structural
      specificity, complexity, and related unique functions. Herein, we highlight the
      synthesis and application of biotemplated materials for six key areas of energy
      and environment technologies, namely, photocatalytic hydrogen evolution, CO(2) 
      reduction, solar cells, lithium-ion batteries, photocatalytic degradation, and
      gas/vapor sensing. Although the applications differ from each other, a common
      fundamental challenge is to realize optimum structures for improved performances.
      We highlight the role of four typical structures derived from biological systems
      exploited to optimize properties: hierarchical (porous) structures, periodic
      (porous) structures, hollow structures, and nanostructures. We also provide
      examples of using biogenic elements (e.g., C, Si, N, I, P, S) for the creation of
      active materials. Finally, we disscuss the challenges of achieving the desired
      performance for large-scale commercial applications and provide some useful
      prototypes from nature for the biomimetic design of new materials or systems. The
      emphasis is mainly focused on the structural effects and compositional
      utilization of biotemplated materials.

PMID- 21905238
TI  - Carbon nanotube-based metal-ion catchers as supramolecular depolluting materials.
AB  - Herein, we report the first example of supramolecular carbon nanotube (CNT)-based
      ion catchers as simple and effective tools for removing divalent metal ions from
      organic solvents. In particular, covalently functionalized multi-walled carbon
      nanotubes (MWCNTs) appended with pyridyl groups self-aggregate in solution into
      bundles in the presence of divalent metal ions (e.g., Cd2+, Cu2+, Ni2+, Pb2+,
      Zn2+). Such self-aggregation behavior leads to insoluble materials that, upon
      treatment with weak acids, can be regenerated and reused for further
      complexation. All materials and complexation/decomplexation steps were thoroughly
      characterized by using X-ray photoelectron spectroscopy (XPS), thermogravimetric
      analysis (TGA), and different microscopy-based techniques, namely, transmission
      electron, scanning electron, and atomic force microscopy (TEM, SEM, and AFM). The
      supramolecular system engineered in this work is the first example of an easy and
      fully sustainable material with great potential applications for depolluting
      liquid waste from metal contamination.

PMID- 21905240
TI  - Prawn lipocalin: characterization of a color shift induced by gene knockdown and
      ligand binding assay.
AB  - The lipocalin family of proteins functions in the transport of steroids,
      carotenoids, retinoids, and other small hydrophobic molecules. Recently, a
      lipocalin (MrLC) was isolated from the prawn Macrobrachium rosenbergii and its
      expression varied with the molting cycle. In this study, knockdown of the MrLC
      gene by RNA interference (RNAi) was performed and resulted in a shift in body
      color from blue to orangish red over the entire carapace. By immune-gold electron
      microscopy, MrLC was found to co-localize with the lipid droplets in subepidermal
      adiose tissue that were found to be decreased dramatically in MrLC knockdown
      prawns, in which a reduction in relative fat content was also quantified.
      Furthermore, MrLC was found to specifically bind astaxanthin and molt hormone (20
      hydroxyecdysone) in both in vitro ligand binding assay and in vivo native ligand
      detection. These results suggested that MrLC plays roles in the regulation of
      coloration through its association with astaxanthin and may also be involved in
      the regulation of molting in crustacean.

PMID- 21905241
TI  - Deconstructing sociability, an autism-relevant phenotype, in mouse models.
AB  - Reduced sociability is a core feature of autism spectrum disorders (ASD) and is
      highly disabling, poorly understood, and treatment refractory. To elucidate the
      biological basis of reduced sociability, multiple laboratories are developing ASD
      relevant mouse models in which sociability is commonly assessed using the Social
      Choice Test. However, various measurements included in that test sometimes
      support different conclusions. Specifically, measurements of time the "test"
      mouse spends near a confined "stimulus" mouse (chamber scores) sometimes support
      different conclusions from measurements of time the test mouse sniffs the
      cylinder containing the stimulus mouse (cylinder scores). This raises the
      question of which type of measurements are best for assessing sociability. We
      assessed the test-retest reliability and ecological validity of chamber and
      cylinder scores. Compared with chamber scores, cylinder scores showed higher
      correlations between test and retest measurements, and cylinder scores showed
      higher correlations with time spent in social interaction in a more naturalistic
      phase of the test. This suggests that cylinder scores are more reliable and valid
      measures of sociability in mouse models. Cylinder scores are reported less
      commonly than chamber scores, perhaps because little work has been done to
      establish automated software systems for measuring the former. In this study, we
      found that a particular automated software system performed at least as well as
      human raters at measuring cylinder scores. Our data indicate that cylinder scores
      are more reliable and valid than chamber scores, and that the former can be
      measured very accurately using an automated video analysis system in ASD-relevant
      models.

PMID- 21905242
TI  - Neonatal exposure of rats to antidepressants affects behavioral reactions to
      novelty and social interactions in a manner analogous to autistic spectrum
      disorders.
AB  - We have demonstrated that neonatal exposure to selective serotonin reuptake
      inhibitors has lasting effects on behavior and serotonergic neurons in Long Evans
      rats. Hyperserotoninemia and altered sensory processing are reported in autistic
      spectrum disorders (ASD). We hypothesized that early life exposure to SSRIs
      alters sensory processing, disrupts responses to novelty, and impairs social
      interactions in a manner similar to that observed in ASD. Male and female Long
      Evans rat pups were administered citalopram, buproprion, fluoxetine, or saline
      from postnatal day (P) 8-21. Rats were tested for response to a novel tone before
      weaning (P25). Later, rats were tested 2* for response to a novel object (P39),
      and to a novel conspecific (P78, P101). In addition, rats were assessed for
      juvenile play behaviors (P32-P34) and later, we assessed sexual response to an
      estrus female in male rats (P153-184). Antidepressant exposure increased freezing
      after tone, diminished novel object exploration, and reduced conspecific
      interaction up to 3* compared to saline exposed rats. Juvenile play was
      profoundly reduced in antidepressant-exposed males when compared to saline
      exposed groups. Exposure to the SSRIs, but not bupropion disrupted male sexual
      behaviors. Moreover, specific male responses to female proceptive behaviors were
      disrupted in SSRI, but not bupropion exposed rats. We conclude that neonatal
      exposure to antidepressants in rats results in sensory and social abnormalities
      that parallel many of those reported in ASD.

PMID- 21905243
TI  - Better fear conditioning is associated with reduced symptom severity in autism
      spectrum disorders.
AB  - Evidence from behavioral and neuroimaging studies suggest that atypical amygdala
      function plays a critical role in the development of autism spectrum disorders
      (ASD). The handful of psychophysiological studies examining amygdala function in
      ASD using classical fear conditioning paradigms have yielded discordant results.
      We recorded skin conductance response (SCR) during a simple discrimination
      conditioning task in 30 children and adolescents (ages 8-18) diagnosed with high
      functioning ASD and 30 age- and IQ-matched, typically developing controls. SCR
      response in the ASD group was uniquely and positively associated with social
      anxiety; and negatively correlated with autism symptom severity, in particular
      with social functioning. Fear conditioning studies have tremendous potential to
      aid understanding regarding the amygdale's role in the varied symptom profile of
      ASD. Our data demonstrate that such studies require careful attention to task
      specific factors, including task complexity; and also to contributions of
      dimensional, within-group factors that contribute to ASD heterogeneity.

PMID- 21905244
TI  - Verbal problem-solving in autism spectrum disorders: a problem of plan
      construction?
AB  - Children with autism spectrum disorders (ASD) adopt less efficient strategies
      than typically developing controls (TD) on verbal problem-solving tests such as
      the Twenty Questions Task. This study examined the hypotheses that this can be
      explained by differences in (i) planning processes or (ii) selective attention.
      Twenty-two children with ASD and 21 TD controls matched for age (M(age) = 13:7)
      and cognitive ability (M(FSIQ) = 96.42) were tested on an adapted version of
      Twenty Questions and two planning tasks. ASD participants could recognize
      effective questions as well as TD participants on a forced-choice question
      discrimination task, but were observed to construct plans that were significantly
      less efficient. ASD performance was also specifically reduced when items could
      not be physically removed from the testing array, although this effect could be
      ameliorated by keeping a written record of participant questions during search.
      These findings indicate that ASD participants are sensitive to the within-task
      executive demands of Twenty Questions, but that their inefficiency in strategy
      relates to planning processes and question selection pretask. The implications
      for understanding ASD problem-solving skills and their impact on everyday
      functioning are discussed.

PMID- 21905245
TI  - Sociodemographic risk factors associated with autism spectrum disorders and
      intellectual disability.
AB  - This study examined the hypotheses that (1) sociodemographic risk factors in
      young children with autism spectrum disorders (ASD) and/or intellectual
      disability (ID) significantly vary by disability type, and (2) measures of income
      (mean adjusted gross income, mean federal taxes paid, and mean tax exemptions)
      significantly increase between 1994 and 2002, and are lower in families with a
      child with ASD and/or ID compared with the general population. A multiple source
      surveillance system utilizing a retrospective record review was used to identify
      ASD and ID cases from a population of 26,108 eight-year-old children born in 1994
      and living in Utah in 2002. ASD without ID (ASD-only, n = 99) cases were
      significantly more likely to be male (P<0.01) and have mothers of White non
      Hispanic ethnicity (P = 0.02). ASD with ID (ASD/ID, n = 33) cases were
      significantly more likely to be male (P<0.01) and have mothers older than 34
      years (P = 0.03). ID without ASD (ID-only, n = 113) cases were significantly more
      likely to have fathers older than 34 years (P<0.01) and were significantly less
      likely to have mothers with >13 years education (P<0.01). Measures of income for
      cases at birth and at 8 years of age were not significantly lower than the
      general population and mean adjusted income of cases significantly increased from
      birth to 8 years of age. Investigations focused on defining early
      sociodemographic risk factors by different endophenotypes of ASD may assist in
      identifying risk factors for this complex group of neurodevelopmental disorders.
      Aggregate tax information may be a unique resource to utilize for population
      based analysis.

PMID- 21905246
TI  - Evidence for broader autism phenotype characteristics in parents from multiple
      incidence autism families.
AB  - The broader autism phenotype (BAP) was assessed in parents who have two or more
      children with autism spectrum disorder (ASD) (multiplex (MPX) autism), parents
      who have no more than one child with ASD (simplex autism), parents who have a
      child with developmental delay without ASD, and parents who have typically
      developing children. Clinicians, naive to parent group membership status, rated
      BAP characteristics from videotaped administration of the Broader Autism
      Phenotype Symptom Scale (BPASS). Differences among groups in BPASS scores in the
      four assessed domains (social motivation, conversational skills, expressiveness,
      and restricted interests) were examined using multivariate ANOVA and post hoc
      comparisons. Further, ratings of videotapes by observers naive to family status
      were compared with live, non-naive ratings by observers who were aware of family
      status (non-naive). Findings demonstrate that the BPASS is an instrument
      resistant to rater bias. Parents from MPX autism families showed significantly
      more autism phenotype characteristics than the parents in the other groups.
      Moreover, the parents from simplex autism families did not differ from the
      parents of children with developmental delay or typical development. Finally, no
      differences between live, non-naive ratings and videotaped, naive ratings were
      observed. These findings suggest that characteristics of the BAP, specifically in
      the social and communication domains, are present in MPX autism parents to a
      greater degree than simplex autism and control parents. Further, the results
      provide support for the notion that genetic transmission mechanisms may differ
      between families with more than one child with autism and families with only one
      child with autism.

PMID- 21905247
TI  - QSRR using evolved artificial neural network for 52 common pharmaceuticals and
      drugs of abuse in hair from UPLC-TOF-MS.
AB  - A quantitative structure-retention relationship (QSRR) study based on an
      artificial neural network (ANN) was carried out for the prediction of the ultra
      performance liquid chromatography-Time-of-Flight mass spectrometry (UPLC-TOF-MS)
      retention time (RT) of a set of 52 pharmaceuticals and drugs of abuse in hair.
      The genetic algorithm was used as a variable selection tool. A partial least
      squares (PLS) method was used to select the best descriptors which were used as
      input neurons in neural network model. For choosing the best predictive model
      from among comparable models, square correlation coefficient R(2) for the whole
      set calculated based on leave-group-out predicted values of the training set and
      model-derived predicted values for the test set compounds is suggested to be a
      good criterion. Finally, to improve the results, structure-retention
      relationships were followed by a non-linear approach using artificial neural
      networks and consequently better results were obtained. This also demonstrates
      the advantages of ANN.

PMID- 21905248
TI  - Changes in hand bone mineral density and the association with the level of
      disease activity in patients with rheumatoid arthritis: bone mineral density
      measurements in a multicenter randomized clinical trial.
AB  - OBJECTIVE: To determine if metacarpal bone mineral density (mBMD) gain occurs in
      patients with rheumatoid arthritis (RA). If mBMD loss is driven by inflammation,
      we expect to find mBMD gain in patients who are in remission. METHODS: mBMD was
      measured by digital x-ray radiogrammetry in consecutive radiographs of 145
      patients with RA with either continuous high disease activity (HDA; Disease
      Activity Score [DAS] >2.4), low disease activity (LDA; 1.6 >= DAS <= 2.4), or
      continuous clinical remission (CR; DAS <1.6) during a 1-year observation period.
      The association of mBMD changes with disease activity was investigated with
      multinomial regression analysis. Next, clinical variables associated with mBMD
      gain were identified. RESULTS: Mean change in mBMD in CR patients was -0.03%,
      compared to -3.13% and -2.03% in HDA and LDA patients, respectively (overall, P <
      0.001). Of the patients in CR, 32% had mBMD loss (less than or equal to -4.6
      mg/cm2/year), compared to 62% and 66% of the patients with HDA or LDA,
      respectively, whereas 26% of the patients in CR had mBMD gain (>=4.6
      mg/cm2/year), compared to 2% of the patients with HDA and 5% of the patients with
      LDA. Patients in CR had a higher chance of having mBMD gain, compared with LDA
      and HDA (relative risk [RR] 14.9, 95% confidence interval [95% CI] 3.0-18.7 and
      RR 4.7, 95% CI 1.2-6.3, respectively). CR, hormone replacement therapy, and lower
      age were significant independent predictors of mBMD gain. CONCLUSION: In RA, mBMD
      gain occurs primarily in patients in continuous (>=1 year) CR and rarely in
      patients with continuous HDA or LDA. This suggests that mBMD loss is driven by
      inflammation.

PMID- 21905249
TI  - Changes in vascular function and structure in juvenile idiopathic arthritis.
AB  - OBJECTIVE: Chronic inflammatory diseases in adults have been associated with
      increased cardiovascular risk and impaired vascular function. We aimed to assess
      the presence of early vascular dysfunction in patients with juvenile idiopathic
      arthritis (JIA) and investigate the role of inherent inflammatory process of JIA
      in vascular health. METHODS: Thirty patients with JIA (age range 7-18 years) were
      compared to 33 age- and sex-matched controls. Endothelial function (brachial
      artery flow-mediated dilation [FMD]), carotid intima-media thickness (IMT), and
      arterial stiffness were examined. Endothelial inflammation was assessed by
      intercellular adhesion molecule 1 (ICAM-1) and P-selectin measurements. RESULTS:
      Patients with JIA showed decreased FMD compared to controls (P = 0.001),
      independent of age (P = 0.9 among age subgroups). Baseline differences in
      erythrocyte sedimentation rate, ICAM-1, and glucose between the 2 groups
      accounted for the difference in FMD. The presence of systemic JIA was associated
      with greater IMT compared to patients with oligoarticular disease, polyarticular
      disease, or controls (P = 0.014, P = 0.069, and P = 0.046, respectively). The
      difference in IMT between systemic versus oligoarticular/polyarticular JIA was
      attributed to the following risk factors: age, body mass index, blood pressure,
      disease activity, and corticosteroids use. There were no differences in arterial
      stiffness indices between JIA patients and controls or between patients with
      systemic versus nonsystemic disease. CONCLUSION: Endothelial function is impaired
      in patients with JIA at a very young age, while IMT is increased only in the
      presence of systemic JIA. Vascular dysfunction may be partly attributed to the
      effects of disease-related characteristics (inflammation, disease activity, and
      medications).

PMID- 21905250
TI  - Identifying common trajectories of joint space narrowing over two years in knee
      osteoarthritis.
AB  - OBJECTIVE: Little is known about the natural history of knee osteoarthritis (OA).
      We sought to identify common patterns of joint space narrowing (JSN) in well
      characterized knee OA patients in the placebo arm of a 2-year international
      study. METHODS: We performed secondary data analyses of 622 adults ages 39-80
      years in North America (n = 310) and Europe (n = 312) with symptomatic knee OA.
      Fluoroscopically positioned semiflexed anteroposterior radiographs were obtained
      at 0, 12, and 24 months. Group-based trajectory modeling was used to identify
      distinctive groups of individuals with similar trajectories of JSN, taking into
      account sex, age, and body mass index. RESULTS: Seven groups were identified.
      Four exhibited joint space width (JSW) stability over 2 years representing the
      most common trajectory (71%), which was unrelated to initial JSW. Atypical
      courses included slow, rapid, and moderate progressors; most had significant JSN
      at study entry. Slow progressors (20%) had a mean JSN of 0.2 mm over 2 years.
      Only 2% of the sample demonstrated rapid JSN (2.1 mm), while 7% had JSN of 0.7
      mm. Rapid progressors tended to be men, while slow and moderate progressors were
      older and heavier. CONCLUSION: Most (70%) people with OA demonstrated no
      significant JSN over 2 years; 20% showed slow progression, 7% had moderate, and
      2% had rapid JSN. Progressors tended to have less JSW at study entry and were
      older and heavier; rapid progressors were more likely to be men. Understanding
      common patterns of the course of knee OA may offer new opportunities to target
      those at greatest risk of disability.

PMID- 21905251
TI  - Associations of knee extensor strength and standing balance with physical
      function in knee osteoarthritis.
AB  - OBJECTIVE: Knee extensor strength is an important correlate of physical function
      in patients with knee osteoarthritis; however, it remains unclear whether
      standing balance is also a correlate. The purpose of this study was to evaluate
      the cross-sectional associations of knee extensor strength, standing balance, and
      their interaction with physical function. METHODS: One hundred four older adults
      with end-stage knee osteoarthritis awaiting a total knee replacement (mean +/- SD
      age 67 +/- 8 years) participated. Isometric knee extensor strength was measured
      using an isokinetic dynamometer. Standing balance performance was measured by the
      center of pressure displacement during quiet standing on a balance board.
      Physical function was measured by the self-report Short Form 36 (SF-36)
      questionnaire and by the 10-meter fast-pace gait speed test. RESULTS: After
      adjustment for demographic and knee pain variables, we detected significant knee
      strength by standing balance interaction terms for both SF-36 physical function
      and fast-pace gait speed. Interrogation of the interaction revealed that standing
      balance in the anteroposterior plane was positively related to physical function
      among patients with lower knee extensor strength. Conversely, among patients with
      higher knee extensor strength, the standing balance-physical function
      associations were, or tended to be, negative. CONCLUSION: These findings suggest
      that although standing balance was related to physical function in patients with
      knee osteoarthritis, this relationship was complex and dependent on knee extensor
      strength level. These results are of importance in developing intervention
      strategies and refining theoretical models, but they call for further study.

PMID- 21905252
TI  - Relationship between beliefs, motivation, and worries about physical activity and
      physical activity participation in persons with rheumatoid arthritis.
AB  - OBJECTIVE: To determine the relationship between beliefs, motivation, and worries
      about physical activity and physical activity participation in persons with
      rheumatoid arthritis (RA). METHODS: A cross-sectional study used baseline data
      from 185 adults with RA enrolled in a randomized clinical trial assessing the
      effectiveness of an intervention to promote physical activity. Data included
      patients' self-reported beliefs that physical activity can be beneficial for
      their disease, motivation for physical activity participation, worries about
      physical activity participation, and average daily accelerometer counts of
      activity over a week's time. Body mass index (BMI), sex, age, race, and disease
      activity were measured as potential statistical moderators of physical activity.
      RESULTS: Physical activity participation was greater for those with higher scores
      on scales measuring beliefs that physical activity is beneficial for their
      disease (P for trend = 0.032) and motivation for physical activity participation
      (P for trend = 0.007) when adjusted for age, sex, BMI, race, and disease
      activity. There was a positive but nonsignificant trend in physical activity
      participation in relation to worries. CONCLUSION: Stronger beliefs that physical
      activity can be helpful for managing disease and increased motivation to engage
      in physical activity are related to higher levels of physical activity
      participation. These data provide a preliminary empirical rationale for why
      interventions targeting these concepts should lead to improved physical activity
      participation in adults with RA.

PMID- 21905253
TI  - Development and validation of a short form of the valued life activities
      disability questionnaire for rheumatoid arthritis.
AB  - OBJECTIVE: To develop and validate a shortened version of the Valued Life
      Activities disability and accommodations scale (VLA) for individuals with
      rheumatoid arthritis (RA). METHODS: To shorten the existing VLA measure, item
      response theory analyses were conducted using data from 449 patients with RA.
      Next, the resulting 14-item shortened version of the VLA scale (S-VLA) was
      evaluated by structured interviews among 20 RA patients. Lastly, the S-VLA was
      administered to 150 RA patients along with other measures, including the Health
      Assessment Questionnaire (HAQ) and Short Form 36 (SF-36). A random sample of 50
      patients completed the S-VLA 2 weeks later to assess reliability. Item statistics
      were calculated to evaluate correlations between individual items and the S-VLA
      total score. Correlations between the S-VLA and other measures were used to
      evaluate validity. RESULTS: Test-retest reliability was 0.91, while Cronbach's
      alpha for the S-VLA was 0.95. None of the 14 items was associated with improved
      alpha coefficients when omitted. All of the items were strongly correlated with
      the S-VLA total score. S-VLA scores were highly positively correlated with the
      HAQ (r = 0.81, P <= 0.001), patient-reported disease activity (r = 0.71, P <=
      0.001), satisfaction with abilities (r = 0.82, P <= 0.001), and number of days
      with activity limitations (r = 0.65, P <= 0.001). In addition, as hypothesized,
      the S-VLA was inversely correlated with the SF-36 physical component summary
      score (r = -0.78, P <= 0.001) and the physical functioning (r = -0.80, P <=
      0.001), role physical (r = -0.67, P <= 0.001), and social functioning (r = -0.72,
      P <= 0.001) subscales. CONCLUSION: The S-VLA is a short, valid, and reliable
      instrument that may prove useful for monitoring disability among individuals with
      RA.

PMID- 21905254
TI  - Experimental knee joint pain during strength training and muscle strength gain in
      healthy subjects: a randomized controlled trial.
AB  - OBJECTIVE: Knee joint pain and reduced quadriceps strength are cardinal symptoms
      in many knee pathologies. In people with painful knee pathologies, quadriceps
      exercise reduces pain, improves physical function, and increases muscle strength.
      A general assumption is that pain compromises muscle function and thus may
      prevent effective rehabilitation. This study evaluated the effects of
      experimental knee joint pain during quadriceps strength training on muscle
      strength gain in healthy individuals. METHODS: Twenty-seven healthy untrained
      volunteers participated in a randomized controlled trial of quadriceps
      strengthening (3 times per week for 8 weeks). Participants were randomized to
      perform resistance training either during pain induced by injections of painful
      hypertonic saline (pain group, n = 13) or during a nonpainful control condition
      with injection of isotonic saline (control group, n = 14) into the infrapatellar
      fat pad. The primary outcome measure was change in maximal isokinetic muscle
      strength in knee extension/flexion (60, 120, and 180 degrees/second). RESULTS:
      The group who exercised with pain had a significantly larger improvement in
      isokinetic muscle strength at all angular velocities of knee extension compared
      to the control group. In knee flexion there were improvements in isokinetic
      muscle strength in both groups with no between-group differences. CONCLUSION:
      Experimental knee joint pain improved the training-induced gain in muscle
      strength following 8 weeks of quadriceps training. It remains to be studied
      whether knee joint pain has a positive effect on strength gain in patients with
      knee pathology.

PMID- 21905255
TI  - Vibratory perception threshold in young and middle-aged patients at high risk of
      knee osteoarthritis compared to controls.
AB  - OBJECTIVE: Vibratory perception threshold (VPT) is impaired in patients with knee
      osteoarthritis (OA). It is, however, not known if sensory deficits precede or
      follow as a consequence of OA. The aim of this study was to investigate VPT in 2
      independent groups of patients with high risk of future OA (young anterior
      cruciate ligament [ACL]-injured patients and middle-aged meniscectomized
      patients) and compare them to age-matched controls. METHODS: VPT was assessed at
      the medial malleolus (MM) and medial femoral condyle (MFC) in 2 independent
      groups of patients and matched controls: ACL-injured patients (n = 39, mean +/-
      SD age 24.0 +/- 5.2 years, mean +/- SD BMI 24.0 +/- 2.9 kg/m(2) , mean +/- SD
      time since injury 21.9 +/- 21.6 months) and controls (n = 28, mean +/- SD age
      25.6 +/- 4.4 years, mean +/- SD BMI 23.6 +/- 2.2 kg/m(2) ), and meniscectomized
      patients (n = 22, mean +/- SD age 49.6 +/- 4.8 years, mean +/- SD BMI 24.7 +/-
      2.7 kg/m(2) , mean +/- SD time since surgery 49.6 +/- 5.0 months) and controls (n
      = 25, mean +/- SD age 49.4 +/- 5.2 years, mean +/- SD BMI 25.2 +/- 4.9 kg/m(2) ).
      RESULTS: ACL-injured patients had a better VPT than controls at the MM (P =
      0.030), which persisted after adjusting for age and sex (P = 0.034). At the MFC,
      there was a similar trend in favor of ACL injured patients (unadjusted P = 0.093,
      adjusted P = 0.122). No differences were seen in VPT at the MM between
      meniscectomized patients and controls, whereas there was a tendency for better
      VPT in meniscectomized patients at the MFC (unadjusted P = 0.085, adjusted P =
      0.092). CONCLUSION: Impaired vibratory sensation could not be confirmed in 2
      independent groups of patients compared to age-matched controls, suggesting that
      impaired vibratory sense is not present in knee-injured patients at high risk or
      in the very early phase of knee OA.

PMID- 21905256
TI  - Association between skeletal muscle inflammatory markers and walking pattern in
      people with knee osteoarthritis.
AB  - OBJECTIVE: Patients with knee osteoarthritis (OA) are characterized by increased
      muscle inflammation and altered gait. We investigated the association between
      proinflammatory mediators in the vastus lateralis and physical function and gait
      in patients with knee OA. METHODS: Nineteen patients with knee OA underwent gait
      analysis, assessment of self-reported pain and physical function (Western Ontario
      and McMaster Universities Osteoarthritis Index [WOMAC]), and a muscle biopsy that
      was taken during their knee replacement surgery. Muscle was analyzed for cellular
      protein inflammatory mediators, interleukin-6, monocyte chemotactic protein 1
      (MCP-1), p65 NF-kappaB, signal transducer and activator of transcription 3 (STAT
      3), and JNK-1. Sagittal plane knee function, including early stance knee range of
      motion (ROM) and knee sagittal plane impulse, was measured using a motion
      analysis system. Pearson's correlation was used to assess relationships between
      selected variables. RESULTS: Significant positive correlations were found between
      MCP-1 and self-perceived stiffness, physical function, and the total WOMAC score
      (P < 0.05). MCP-1 was also negatively correlated with early stance knee ROM (r = 
      0.52, P = 0.023). Reduced velocity was associated with elevated levels of p65 NF
      kappaB and STAT-3 (P < 0.05). Knee sagittal plane impulse was negatively
      correlated with JNK-1 (P = 0.02), indicating reduction in knee impulse with an
      increased level of JNK-1. CONCLUSION: Increased levels of several proinflammatory
      mediators were correlated with altered knee function during walking as well as
      greater physical disability and slower gait velocity. Identification of the
      cellular and molecular mechanisms associated with muscle inflammation is
      important to better understand the underlying mechanism responsible for altered
      gait and function in patients with knee OA.

PMID- 21905257
TI  - Recovery expectations of hip resurfacing compared to total hip arthroplasty: a
      matched pairs study.
AB  - OBJECTIVE: Expectations of higher activity levels associated with hip resurfacing
      arthroplasty (HRA) may be driving better outcomes in this group compared to total
      hip arthroplasty (THA). Previous studies evaluated patient expectations before
      consulting with the surgeon, although these expectations were likely unrealistic
      and would change after the consultation. We compared HRA and THA patient
      expectations after consultation with the surgeon. METHODS: In a prospective
      registry setting, patients awaiting HRA were matched to THA patients by age, sex,
      and a preoperative Lower Extremity Activity Scale score (range 1-18, with 18
      indicating levels of highest activity). Patients completed preoperatively a
      validated 18-item expectations survey. Mean overall expectation scores were first
      compared. Exploratory factor analysis (EFA) was then performed to determine if
      the grouping of individual expectations items represented meaningfully different
      underlying factors in the 2 groups. RESULTS: We matched 123 pairs. The mean +/-
      SD expectation scores were similar (85.2 +/- 15.5 for HRA and 87.3 +/- 13.9 for
      THA; P = 0.249). The EFA showed that HRA and THA patients shared the common
      expectations of pain relief and improvement in daily activities (9 items) and
      eliminating pain medications, the need for a cane, and improving sexual activity
      (3 items). THA patients perceived the remaining 6 items as an overall third
      expectation of participation in higher-level activities. However, HRA patients
      perceived a fourth expectation of normal range of motion (2 items) independent of
      the other higher-level activities (4 items). CONCLUSION: Even after consulting
      with a surgeon, patients' expectations differed between HRA and THA patients
      regarding higher-level activities. More counseling for patients seeking hip
      arthroplasty is therefore needed.

PMID- 21905258
TI  - Cardiovascular and other comorbidities in patients with psoriatic arthritis: a
      comparison with patients with psoriasis.
AB  - OBJECTIVE: To determine whether the presence of psoriatic arthritis (PsA) is
      associated with greater comorbidity, in particular cardiovascular morbidity,
      compared to psoriasis without arthritis. METHODS: Six hundred eleven patients
      with PsA were recruited from the University of Toronto Psoriatic Arthritis Clinic
      and 449 psoriasis without arthritis patients were recruited from the University
      of Toronto Psoriasis Cohort. The clinical database was used to identify the
      prevalence of cardiovascular and other comorbidities in both PsA and psoriasis
      without arthritis patients. Univariate and multivariate logistic regression
      analyses were conducted to estimate odds ratios (ORs), comparing the odds of ever
      having a given comorbid disease in PsA patients with those in psoriasis without
      arthritis patients. Covariates included age, sex, education, smoking status,
      severity and duration of psoriasis, medication status, and other comorbidities.
      RESULTS: The prevalence of hypertension, obesity, hyperlipidemia, type 2 diabetes
      mellitus, and at least 1 cardiovascular event in PsA patients was 37.1%, 30.0%,
      20.7%, 12.0%, and 8.2%, respectively. This was significantly higher than in
      psoriasis without arthritis patients, with unadjusted ORs ranging from 1.54 to
      2.59. In the multivariate analyses, hypertension remained significantly elevated
      (adjusted OR 2.17). PsA was also significantly associated with infections not
      treated with antibiotics (presumably viral), neurologic conditions,
      gastrointestinal disorders, and liver disease (adjusted ORs 2.83, 4.76, 21.53,
      and 7.74, respectively). Infections treated with antibiotics and
      depression/anxiety were relatively common in PsA, with a prevalence of 30.5% and
      20.7%, respectively. However, this was not significantly different from psoriasis
      without arthritis after multivariate adjustments. CONCLUSION: The results suggest
      that inflammatory joint disease may play a role in both cardiovascular and
      noncardiovascular morbidity in PsA.

PMID- 21905259
TI  - Longitudinal changes in intermuscular fat volume and quadriceps muscle volume in
      the thighs of women with knee osteoarthritis.
AB  - OBJECTIVE: To quantify rates of change in quadriceps muscle (QM) and
      intermuscular fat (IMF) volumes over 2 years in women in the Osteoarthritis
      Initiative (OAI) study and examine group differences between those with
      radiographic osteoarthritis (ROA) and those without ROA. METHODS: The OAI
      database was queried for women >=50 years of age in the incident and progression
      cohorts with and without ROA at baseline. Midthigh magnetic resonance imaging
      scans (15 contiguous slices, 5 mm slice thickness) of eligible women were
      randomly selected and anonymized. Image pairs were registered. QM and IMF were
      segmented in the 12 most proximal matching slices with the segmenter blinded to
      image time point. Age-adjusted differences in QM and IMF volume changes between
      groups were tested using analysis of covariance. RESULTS: Forty-one women without
      ROA (mean +/- SD age 60.7 +/- 7.6 years) and 45 women with ROA (mean +/- SD age
      64.5 +/- 6.7 years) were included. Mean +/- SD QM and IMF volume changes in the
      non-ROA group were -4.1 +/- 11.1 cm(3) and 3.4 +/- 7.1 cm(3), respectively, and 
      5.4 +/- 13.5 cm(3) and 3.1 +/- 7.4 cm(3) in the ROA group, respectively. Age
      adjusted between-group differences in QM and IMF changes were not significant (P
      > 0.05). CONCLUSION: Two-year changes in QM and IMF volumes appear consistent
      with aging and do not seem to be related to OA status. Direct comparison with a
      control cohort without OA risk factors could confirm this. Since group assignment
      was based on baseline data, there may have been women in the non-ROA group who
      developed ROA over followup, resulting in some overlap between groups.

PMID- 21905261
TI  - Somatoform respiratory disorders in children and adolescents-proposals for a
      practical approach to definition and classification.
AB  - Somatoform respiratory disorders represent conditions with dysfunctional
      breathing unexplained by structural abnormalities. This heterogeneous group
      includes disorders with neural dysregulation of respiration (vocal cord
      dysfunction) or with dysregulation of the respiratory pattern (hyperventilation,
      sighing dyspnea), psychogenic disorders such as unjustified anxiety of
      suffocation, and stereotype conditions such as throat clearing or habit cough.
      Many symptoms are nonspecific and largely overlap with respiratory disease
      symptoms of somatic etiology. Most patients will present in a nonspecialized
      clinical setting. This article provides symptom-based criteria for the definition
      of somatoform respiratory disorders and their differentiation from somatic
      disease. Emphasis is put on clinical criteria which can be easily integrated in a
      routine setting. Owing to the multifaceted etiology of somatoform respiratory
      disorders therapeutic approaches integrating somatic medicine, respiratory
      therapy and psychology are crucial. The introduction of defined clinical criteria
      may facilitate the discrimination of somatoform respiratory disorders from
      somatic disorders in routine patient encounters and avoid therapeutic detours.

PMID- 21905260
TI  - Merging Veterans Affairs rheumatoid arthritis registry and pharmacy data to
      assess methotrexate adherence and disease activity in clinical practice.
AB  - OBJECTIVE: The Veterans Affairs (VA) Rheumatoid Arthritis (VARA) registry and the
      VA Pharmacy Benefits Management database were linked to determine the association
      of methotrexate (MTX) adherence with rheumatoid arthritis (RA) disease activity.
      METHODS: For each patient, the medication possession ratio (MPR) was calculated
      for the first episode of MTX exposure of a duration of >=12 weeks for both new
      and established MTX users. High MTX adherence was defined as an MPR >=0.80 and
      low MTX adherence was defined as an MPR <0.80. For each patient, the mean Disease
      Activity Score with 28 joints (DAS28) score, erythrocyte sedimentation rate
      (ESR), and C-reaction protein (CRP) level observed during registry followup were
      compared in high- versus low-adherence groups. RESULTS: In 455 RA patients, the
      prescribed doses of MTX (mean +/- SD 16 +/- 4 mg versus 16 +/- 4 mg; P = 0.6)
      were similar in high-adherence patients (n = 370) in comparison to low-adherence
      patients (n = 85). However, the actual observed MTX doses taken by patients were
      significantly higher in the high-adherence group (mean +/- SD 16 +/- 5 mg versus
      11 +/- 3 mg; P < 0.001). DAS28 (mean +/- SD 3.6 +/- 1.2 versus 3.9 +/- 1.5; P <
      0.02), ESR (mean +/- SD 24 +/- 18 versus 29 +/- 24 mm/hour; P = 0.05), and CRP
      level (mean +/- SD 1.2 +/- 1.3 versus 1.6 +/- 1.5 mg/dl; P < 0.03) were lower in
      the high-adherence group compared to those with low MTX adherence. These
      variances were not explained by differences in baseline demographic features,
      concurrent treatments, or whether MTX was initiated before or after VARA
      enrollment. CONCLUSION: High MTX adherence was associated with improved clinical
      outcomes in RA patients treated with MTX. Adjustment for potential confounders
      did not alter the estimated effect of adherence. These results demonstrate the
      advantages of being able to merge clinical observations with pharmacy databases
      to evaluate antirheumatic drugs in clinical practice.

PMID- 21905262
TI  - Impaired behavioral and neurocognitive function in preschool children with
      obstructive sleep apnea.
AB  - OBJECTIVE: We aimed to examine the hypothesis that behavioral and neurocognitive
      functions of preschool children with Obstructive Sleep Apnea Syndrome (OSAS) are
      impaired compared to healthy children, and improve after adenotonsillectomy (TA).
      METHODS: A comprehensive assessment battery was used to assess cognitive and
      behavioral functions, and quality of life in children with OSAS compared to
      matched controls. RESULTS: 45 children (mean age 45.5 +/- 9 months, 73% boys, BMI
      15.7 +/- 2) with OSAS were compared to 26 healthy children (mean age 48.6 +/- 8
      months, 46% boys, BMI 16.4 +/- 2). Mean AHI in the OSAS group was 13.2 +/- 10.7
      (ranging from 1.2 to 57). Significantly impaired planning and fluency (executive
      function) were found in children with OSAS, as well as impaired attention and
      receptive vocabulary. Parents and teachers described the OSAS group as having
      significantly more behavior problems. Quality of life questionnaire in children
      with OSAS (mean 2.3, range 0.7-4.3) was significantly worse compared to controls
      (mean 0, range: 0-4), P < 0.004. One year following TA, 23 children with OSAS and
      18 controls were re-evaluated. Significant improvement was documented in verbal
      and motor fluency, sustained attention, and vocabulary. After TA, fewer
      behavioral problems were seen. CONCLUSIONS: Preschool children with OSAS present
      significantly impaired executive functions, impaired attention and receptive
      vocabulary, and more behavior problems. One year after TA, the prominent
      improvements were in behavior and quality of life. These findings suggest that
      the impact of OSAS on behavioral and cognitive functions begins in early
      childhood.

PMID- 21905263
TI  - Fifty years of pediatric asthma in developed countries: how reliable are the
      basic data sources?
AB  - Given the difficulties in diagnosing, or even defining, asthma in children,
      claims of a pediatric asthma epidemic in Canada and other developed countries are
      accepted with surprisingly little critical examination. We reviewed a broad range
      of data sources to understand how the epidemic evolved during the last 50 years
      and also to assess the reliability of the conclusions drawn from that data. We
      obtained Canadian National and Provincial data from Statistics Canada National
      Population Health Survey, and the British Columbia Ministry of Health respiratory
      database. International data were obtained by extensive review of pediatric
      asthma epidemiological surveys published during the last 50 years. In many
      developed countries, there have been three separate epidemics involving different
      aspects of pediatric asthma during the last 50 years: a double peaked mortality
      epidemic (1960s and 1980s), a hospital admission epidemic (peaked around 1990)
      and a steadily growing epidemic of children who report asthmatic symptoms on
      questionnaires. Canadian pediatric rates for asthma mortality (1-2/million/year)
      and hospital admission (1-2/thousand/year) are low and have fallen for the last
      20 years. Rates based on questionnaire studies are high (10-15/hundred) and rose
      steadily over the same period. Objective reductions in asthma deaths and hospital
      admission likely reflect improved education and treatment programmes. Current
      claims of an epidemic based largely on subjective self-reported symptoms require
      more careful analysis. The possibility that symptom misperception, disease
      fashions, and poor recall, may be part of the explanation for the current high
      levels of self-reported symptoms deserves more attention.

PMID- 21905264
TI  - Aspergilloma in a patient with an occult congenital pulmonary airway
      malformation.
AB  - We describe the case of a 14-year-old male who presented with a right upper lobe
      aspergilloma forming in a previously occult congenital pulmonary airway
      malformation. This is the first case describing an aspergilloma forming within a
      CPAM.

PMID- 21905265
TI  - Hyperoxia arrests alveolar development through suppression of histone
      deacetylases in neonatal rats.
AB  - Bronchopulmonary dysplasia (BPD) poses a significant global health problem. It
      mainly occurs in preterm infants. It is histopathologically characterized by
      fewer and larger alveoli and less secondary septa, suggesting an arrested or
      disordered lung development. To date, the mechanisms that lead to the
      pathophysiological changes in BPD have still not been totally understood. In
      embryonic development, histone deacetylase (HDAC) plays an important role by
      regulating gene transcription. Here, we hypothesize that a decreased HDAC
      expression and activity, caused by preterm birth or environmental stresses,
      contribute to a disorder in alveolar development in BPD. To this end, newborn
      Sprague-Dawley rats subjected to hyperoxia (85% O(2) ) were used to investigate
      the gene expression and protein activity of HDAC and alveolar development in
      lungs. Our results showed that hyperoxia exposure led to a suppression of the
      HDAC1/HDAC2 expression and activity, and the overall HDAC activity, as well as
      arrest of alveolarization, and an elevated expression of the cytokine-induced
      neutrophil chemoattractant-1 (CINC-1) in the lungs of newborn rats. However,
      preservation of HDAC activity by theophylline significantly improved alveolar
      development and attenuated CINC-1 release, all of which were blocked by a
      specific HDAC inhibitor, trichostatin A (TSA). TSA alone can disturb the alveolar
      development in neonatal rats. Our findings indicate that a persistent exposure to
      hyperoxia leads to a suppressed HDAC activity, which causes disorders in
      pulmonary development. This effect may be mediated by CINC-1. Attenuation of CINC
      1-mediated inflammation by activating HDAC may have a protective effect in BPD.

PMID- 21905266
TI  - Fetal hyperglycemia alters lung structural development in neonatal rat.
AB  - Maternal diabetes is associated with increased risk for abnormal fetal
      organogenesis, but its effects on the developing lungs are still insufficiently
      known. To determine the effect of maternal hyperglycemia on postnatal lung
      development, we studied lung structural and cellular changes in newborn rats
      exposed to intrauterine hyperglycemia. We induced hyperglycemia in Sprague-Dawley
      rats with i.p. streptozotocin before pregnancy and allowed the hyperglycemic and
      control dams deliver at term. Lungs were obtained on postnatal day (d) 0, d7, and
      d14 and analyzed for lung weight and morphology, as well as cellular apoptosis
      (TUNEL staining) and proliferation (PCNA staining). Quantitative micro-CT
      analysis of the lung vasculature was additionally performed at d14. At birth,
      maternal hyperglycemia resulted in decreased relative lung weight, thinner
      alveolar septa and increased cellular apoptosis and proliferation, when compared
      to controls. At 1 and 2 weeks of age pulmonary cell apoptosis and alveolar chord
      length remained unchanged, but cell proliferation and number of secondary crests
      were increased in the hyperglycemia-exposed neonatal lungs in comparison with the
      controls. Density of small arterioles on histological examination and the
      structure of pulmonary arterial vasculature in micro-CT analysis of the neonatal
      lungs were not influenced by maternal hyperglycemia. Our results suggest, that
      maternal hyperglycemia is related to developmental structural alterations in
      postnatal rat lungs. These early changes may reflect aberrant maturational
      adaptation in response to the hyperglycemic fetal environment.

PMID- 21905267
TI  - Obstructive sleep apnea in poorly controlled asthmatic children: effect of
      adenotonsillectomy.

PMID- 21905268
TI  - Beta-adrenergic receptor polymorphisms associated with length of ICU stay in
      pediatric status asthmaticus.
AB  - BACKGROUND: During severe exacerbations, asthmatic children vary significantly in
      their response to high-dose continuous beta(2) -adrenergic receptor (ADRbeta(2) )
      agonist therapy. Genetic polymorphisms have been identified within the ADRbeta(2)
      that may be functionally relevant, but few studies have been performed in this
      population. Our hypothesis was that genotypic differences are associated with
      magnitude of response to ADRbeta(2) agonist treatment during severe asthma
      exacerbations in children. METHODS: Children aged 2-18 years admitted to the ICU
      (intensive care unit) with a severe asthma exacerbation between 2006 and 2008
      were eligible. Genotyping of the ADRbeta(2) was performed. RESULTS: Eighty-nine
      children consented and were enrolled. Despite similar clinical asthma scores on
      admission, children with the Gly(16) Gly genotype at amino acid position 16 had
      significantly shorter ICU length of stay (LOS) and hospital LOS, compared to
      children with Arg(16) Arg and Arg(16) Gly genotypes. Children with either the
      Gln(27) Glu or Glu(27) Glu genotype at amino acid position 27 also had
      significantly shorter ICU LOS and hospital LOS compared to children with the
      Gln(27) Gln genotype. The Arg(16) Gly-Gln(27) Gln haplotype was associated with
      the longest ICU LOS, but this was not statistically different from other
      haplotypes. CONCLUSIONS: In this cohort of children with severe asthma
      exacerbations, ADRbeta(2) polymorphisms were associated with responses to
      therapy. Knowledge of the genetic profile of children with asthma may allow for
      targeted therapy during acute exacerbations.

PMID- 21905269
TI  - Exhaled breath temperature and exercise-induced bronchoconstriction in asthmatic
      children.
AB  - It has been hypothesized that exhaled breath temperature (EBT) is related to the
      degree of airway inflammation/remodeling in asthma. The purpose of this study was
      to evaluate the relationship between the level of airway response to exercise and
      EBT in a group of controlled or partly controlled asthmatic children. Fifty
      asthmatic children underwent measurements of EBT before and after a standardized
      exercise test. EBT was 32.92 +/- 1.13 and 33.35 +/- 0.95 degrees C before and
      after exercise, respectively (P < 0.001). The % decrease in FEV(1) was
      significantly correlated with the increase in EBT (r = 0.44, P = 0.0013), being r
      = 0.49 (P < 0.005) in the children who were not receiving regular inhaled
      corticosteroids (ICS) and 0.37 (n.s.) in those who were. This study further
      supports the hypothesis that EBT can be considered a potential composite tool for
      monitoring asthma.

PMID- 21905270
TI  - A multi-center controlled trial of growth hormone treatment in children with
      cystic fibrosis.
AB  - OBJECTIVES: We evaluated safety and efficacy of recombinant human growth hormone
      (rhGH) for improving growth, lean body mass (LBM), pulmonary function, and
      exercise tolerance in children with cystic fibrosis (CF) and growth restriction.
      STUDY DESIGN: Multicenter, open-label, controlled clinical trial comparing
      outcomes in prepubertal children <14 years with CF, randomized in a 1:1 ratio to
      receive daily rhGH (Nutropin AQ) or no treatment (control) for 12 months,
      followed by a 6-month observation (month 18). Safety was monitored at each visit,
      including assessments of glucose tolerance. RESULTS: Sixty-eight subjects were
      randomized (control n = 32; rhGH n = 36). Mean height standard deviation score
      (SDS) in the rhGH group increased by 0.5 +/- 0.4 at 12 months (mean +/- SD, P <
      0.001); the control group height SDS remained unchanged. Weight increased by 3.8
      +/- 1.8 versus 2.8 +/- 1.5 kg, (mean +/- SD, P = 0.0356) and LBM increased by 3.8
      +/- 1.8 versus 2.1 +/- 1.4 kg (P = 0.0002) in the rhGH group versus controls,
      respectively. Forced vital capacity increased by 325 +/- 319 in the rhGH group
      compared with 178 +/- 152 ml in controls (mean +/- SD, P = 0.032). Forced
      expiratory volume in 1 sec improved in both groups with a significant difference
      between groups after adjustment for baseline severity (LS mean +/- SE: rhGH, 224
      +/- 37, vs. controls, 108 +/- 40 ml; P = 0.04). There was no difference between
      groups in exercise tolerance (6-min walk distance) at 1 year. Changes in glucose
      tolerance for the two groups were similar over the 12-month study period, with
      three subjects developing IGT and one CFRD in each group. One rhGH-treated
      patient developed increased intracranial pressure. CONCLUSIONS: Treatment with
      rhGH in prepubertal children with CF was effective in promoting growth, weight,
      LBM, lung volume, and lung flows, and had an acceptable safety profile.

PMID- 21905271
TI  - Respiratory medication adherence in chronic lung disease of prematurity.
AB  - BACKGROUND: Chronic lung disease of prematurity (CLDP) is a frequent complication
      of premature birth. Infants and children with CLDP are often prescribed complex
      medication regimens, which can be difficult for families to manage. OBJECTIVE: We
      sought to determine whether non-adherence was associated with increased CLDP
      related morbidities and to identify predictors of adherence. METHODS: Recruited
      caregivers of 194 children with CLDP completed questionnaires regarding self
      reported adherence, respiratory outcomes, and quality of life (January 2008-June
      2010). Adherence data were available for 176 subjects, of whom 143 had self
      reported data only, and 33 had prescription claims data, which were used to
      calculate a medication possession ratio (MPR). Participants in the Prescription
      Claims Sample (n = 33) were more likely to have public insurance (P < 0.001).
      RESULTS: Self-reported adherence substantially overestimated medication
      possession; the mean MPR was 38.8% (n = 33) and was not associated with self
      reported adherence (P = 0.71; n = 26). In a small sample, higher MPR was
      associated with decreased odds ratios of visiting the emergency department (ED)
      (OR = 0.75 for a 10% increase in MPR [95%CI: 0.58, 0.97]; P = 0.03; n = 74
      questionnaires from 28 participants), activity limitations (OR = 0.71 [95%CI:
      0.53, 0.95]; P = 0.02; n = 70 questionnaires from 28 participants), and rescue
      medication use (OR = 0.84 [95%CI: 0.73-0.98]; P = 0.03; n = 70 questionnaires
      from 28 participants). Increasing caregiver worries regarding medication efficacy
      and side effects were associated with lower MPR (P = 0.04 and 0.02, respectively;
      n = 62 questionnaires from 27 participants). Socio-demographic and clinical risk
      factors were not predictors of MPR (n = 33). CONCLUSIONS: We found that non
      adherence with respiratory medications was common in premature infants and
      children with CLDP. Using multiple timepoints in a small sample, non-adherence
      was associated with a higher likelihood of respiratory morbidities. Although self
      reported adherence and demographic characteristics did not predict MPR, concerns
      about medications did. We suggest that addressing caregiver concerns about
      medications may improve adherence and ultimately decrease CLDP-related
      morbidities. Larger, prospective studies are needed to confirm these findings and
      determine which factors predict non-adherence.

PMID- 21905272
TI  - Scaled-up separation of cellobiohydrolase1 from a cellulase mixture by ion
      exchange chromatography.
AB  - Enzymatic hydrolysis of cellulose often involves cellulases produced by
      Trichoderma reesei, of which cellobiohydrolase1 (CBH1) is the most abundant
      (about 60% of total cellulases) and plays an important role in the hydrolysis of
      crystalline cellulose. A method for separating sufficient quantities from the
      bulk cellulase cocktail is highly desirable for many studies, such as those that
      aim to characterize binding and hydrolysis kinetics of CBH1. In this work, CBH1
      was separated from other Spezyme CP cellulases by ion-exchange chromatography
      using an efficient modification of a smaller scale process. The ion-exchange
      column was connected to a vacuum manifold system to provide a steady flow through
      parallel columns and thus achieve scale-up for enzyme separation. With five 5-mL
      columns running in parallel, about 55 mg of CBH1 was separated from 145 mg of
      Spezyme CP in a single separation. Step elution was used to replace the
      continuous gradient used at smaller scale. The purified CBH1 was collected in the
      fraction eluted with a buffer containing 0.33 M salt and showed comparable purity
      and activity as the enzyme purified by a fast protein liquid chromatography
      system. The stability of separated CBH1 was studied for up to 2 days and good
      thermal stability was observed. Separated CBH1 also showed both high adsorption
      to bacterial microcrystalline cellulose with ~4 MUmol/g maximum adsorption and a
      K(a) of 5.55 +/- 2.34 MUM(-1) , and good hydrolytic activity based on atomic
      force microscopy observations that show a reduction in fiber height.

PMID- 21905273
TI  - Improved E. coli erythromycin A production through the application of metabolic
      and bioprocess engineering.
AB  - In this report, small-scale culture and bioreactor experiments were used to
      compare and improve the heterologous production of the antibiotic erythromycin A
      across a series of engineered prototype Escherichia coli strains. The original
      strain, termed BAP1(pBPJW130, pBPJW144, pHZT1, pHZT2, pHZT4, pGro7), was designed
      to allow full erythromycin A biosynthesis from the exogenous addition of
      propionate. This strain was then compared against two alternatives hypothesized
      to increase final product titer. Strain TB3(pBPJW130, pBPJW144, pHZT1, pHZT2,
      pHZT4, pGro7) is a derivative of BAP1 designed to increase biosynthetic pathway
      carbon flow as a result of a ygfH deletion; whereas, strain TB3(pBPJW130,
      pBPJW144, pHZT1, pHZT2, pHZT4-2, pGro7) provided an extra copy of a key
      deoxysugar glycosyltransferase gene. Production was compared across the three
      strains with TB3(pBPJW130, pBPJW144, pHZT1, pHZT2, pHZT4, pGro7) showing
      significant improvement in erythronolide B (EB), 3-mycarosylerythronolide B
      (MEB), and erythromycin A titers. This strain was further tested in the context
      of batch bioreactor production experiments with time-course titers leveling at 4
      mg/L, representing an approximately sevenfold increase in final erythromycin A
      titer.

PMID- 21905274
TI  - Evaluation of Escherichia coli proteins that burden nonaffinity-based
      chromatography as a potential strategy for improved purification performance.
AB  - Escherichia coli is a favored host for rapid, scalable expression of recombinant
      proteins for academic, commercial, or therapeutic use. To maximize its economic
      advantages, however, it must be coupled with robust downstream processes.
      Affinity chromatography methods are unrivaled in their selectivity, easily
      resolving target proteins from crude lysates, but they come with a significant
      cost. Reported in this study are preliminary efforts to integrate downstream
      separation with upstream host design by evaluating co-eluting host proteins that
      most severely burden two different nonaffinity-based column processes.
      Phosphoenolpyruvate carboxykinase and peptidase D were significant contaminants
      during serial purification of green fluorescent protein (GFP) by hydrophobic
      interaction and anion exchange chromatography. Ribosomal protein L25 dominated
      non-target binding of polyarginine-tagged GFP on cation exchange resin.
      Implications for genetic knockout or site-directed mutagenesis resulting in
      diminished column retention are discussed for these and other identified
      contaminants.

PMID- 21905275
TI  - Precipitation of filamentous bacteriophages for their selective recovery in
      primary purification.
AB  - Filamentous bacteriophages and their derivatives are showing great promise as a
      whole new class of industrial agents, such as biologically based nano-materials
      and viral vectors. This raises challenges for their large-scale manufacture,
      principally due to the lack of bioprocessing knowledge. This article addresses
      what will be a potentially important option in the primary purification of the
      bacteriophages. Polyethylene glycol (PEG)-salt dual precipitants, calcium ions,
      spermidine, and isoelectric precipitation were first examined for their potential
      suitability for bacteriophage concentration under both pure and broth conditions.
      Successful precipitants were further studied on the basis of their selective
      purification ability from DNA and protein contaminants in a clarified broth
      system. Both PEG-based and isoelectric precipitations resulted in bacteriophage
      purity improvements, and PEG-based precipitations offered the highest
      selectivities. This work shows that precipitation of bacteriophages can be an
      effective primary purification step in a large-scale bioprocess.

PMID- 21905276
TI  - Thermal therapy in dialysis patients - a randomized trial.
AB  - The aim of this study is to evaluate the effects of far-infrared (FIR) rays on
      the meridian in hemodialysis (HD) patients. End-stage renal disease or kidney
      failure is the last stage of chronic renal failure, and often implies that the
      renal function cannot be restored and HD or kidney transplantation is required as
      a life-saving measure. HD patients often feel sick, debilitated, demotivated, and
      sad. A quasi-experimental design was conducted using convenience sampling with 61
      HD patients from a hemodialysis center. Meridian testing and Brief Fatigue
      Inventory-Taiwan Form (BFI-T) were used as screening test for HD. The
      experimental group (n = 36) received FIR irradiation on each acupoint for 30 min,
      thrice a week, for two months, whereas the control group (n = 25) received no
      intervention. The outcome measures included meridian equipment, the level of
      hemoglobin (Hb), albumin, blood urea nitrogen (BUN), creatinine (CRE), and BFI-T.
      Ryodoraku values reveal a significant increase (p < 0.05) in the left small
      intestine meridian, left large intestine meridian, and yin-yang ratio. Overall,
      the increase in the meridians of the patients of experimental group is
      significantly higher than that of the control group. The results establish that
      FIR treatment on Qihai (RN 6), Guanyuan (RN 4), Zhongji (RN 3), and Tianshu (ST
      25) is effective. Based on these findings, one can believe that FIR regulates the
      Qi of the kidney. The findings of this study would help doctors effectively
      dealing with thermal therapy treatment of HD patients.

PMID- 21905277
TI  - Inhibition of endoplasm reticulum stress by anisodamine protects against
      myocardial injury after cardiac arrest and resuscitation in rats.
AB  - Anisodamine is a multi-functional bio-alkaloid with vascular activity. Our
      previous studies have revealed that anisodamine protects the heart from
      ischemia/reperfusion (I/R) injury induced by cardiac arrest (CA) and
      resuscitation. This study aimed to explore whether the protective effect of
      anisodamine is mediated by inhibition of the endoplasmic reticulum stress (ERS)
      response, which has been demonstrated to implicate in various I/R injuries. After
      5 min of CA induced by electric stimulation, Wistar rats were randomly selected
      to receive cardiopulmonary resuscitation (CPR, including chest compression and
      epinephrine infusion) with or without anisodamine injection (n = 50/group).
      Hearts were harvested 24 h after the return of spontaneous circulation (ROSC).
      Sham-operated animals served as non-ischemic controls (n = 10). The survival
      rate, cardiomyocyte apoptosis, and the protein expression of ERS markers were
      detected. Thirty-three of the 50 rats in the Ani + CA/R group were successfully
      resuscitated, whereas only 18 of the 50 rats in the CA/R group gained ROSC.
      Survival to 24 h was significantly improved in the anisodamine treatment group
      (Ani + CA/R, n = 22/50) compared to the group with standard CPR (CA/R, n = 8/50).
      Anisodamine markedly decreased the number of apoptotic cardiomyocytes, the
      protein expression of GRP78, CHOP, and the active form of Caspase3 compared to
      the CA/R group. Our data suggest that anisodamine protects against cellular
      damage in rat hearts after CA and resuscitation, at least in part, by inhibiting
      myocardial ERS.

PMID- 21905279
TI  - Treatment with Astragalus membranaceus produces antioxidative effects and
      attenuates intestinal mucosa injury induced by intestinal ischemia-reperfusion in
      rats.
AB  - Astragalus membranaceus, also known as huang qi, a traditional Chinese medicine,
      is often used in formulas for deficiency of vital energy characterized by limb
      weakness, pale face, and dizziness. Previous studies have shown that Astragalus
      membranaceus could attenuate intestinal ischemia-reperfusion injury induced by
      hemorrhagic shock in rats; however, the underlying mechanism still remains
      unclear. Using a hemorrhagic shock rat model to examine the effect of Astragalus
      membranaceus on intestinal mucosa injury induced by ischemia-reperfusion, we
      found that treatment (20 g crude drugs/kg, i.v.) produced antioxidative effects
      in the intestinal mucosa of rats after ischemia-reperfusion (p < 0.05). We also
      found that Astragalus membranaceus could partly attenuate intestinal mucosa
      ischemia-reperfusion injury (chiu's score, apoptosis index p < 0.05). These
      results suggest that Astragalus membranaceus reduces intestinal mucosa injury
      induced by ischemia-reperfusion in rats, at least in part, through its anti
      oxidative effects.

PMID- 21905278
TI  - Vasorelaxant effect of Cinnamomi ramulus ethanol extract via rho-kinase signaling
      pathway.
AB  - The Rho-kinase (ROCK) signaling pathway is substantially involved in vascular
      contraction. This study investigated the vasodilatory effects and possible
      mechanisms of Cinnamomi ramulus ethanol extract (CRE), with the hypothesis that
      the CRE vasodilatory effect involves RhoA and the ROCK signaling pathway in rat
      aortic preparations. CRE (0.05-1 mg/ml) dose-dependently relaxed the vascular
      contraction induced by phenylephrine and calpeptin in an endothelium-independent
      manner. Measurement of the expression levels of ROCK-related signaling molecules
      in response to calpeptin revealed that CRE completely inhibited RhoA and ROCK2
      protein expressions. Furthermore, CRE dephosphorylated the subsequent downstream
      targets myosin phosphatase targeting subunit 1 (MYPT-1), protein kinase C
      potentiated phosphatase inhibitor protein-17 kDa (CPI-17) and myosin light chain
      20 kDa (MLC20). We conclude that the vasorelaxation effect of CRE occurs via
      downregulation of ROCK signal molecules.

PMID- 21905280
TI  - Effect of Cuscuta chinensis on renal function in ischemia/reperfusion-induced
      acute renal failure rats.
AB  - The kidneys play a central role in regulating water, ion composition and
      excretion of metabolic waste products in the urine. Cuscuta chinensis has been
      known as an important traditional Oriental medicine for the treatment of liver
      and kidney disorders. Thus, we studied whether an aqueous extract of Cuscuta
      chinensis (ACC) seeds has an effect on renal function parameters in
      ischemia/reperfusion-induced acute renal failure (ARF) rats. Administration of
      250 mg/kg/day ACC showed that renal functional parameters including urinary
      excretion rate, osmolality, Na(+), K(+), Cl(-), creatinine clearance, solute-free
      water reabsorption were significantly recovered in ischemia/reperfusion-induced
      ARF. Periodic acid Schiff staining showed that administration of ACC improved
      tubular damage in ischemia/reperfusion-induced ARF. In immunoblot and
      immunohistological examinations, ischemia/reperfusion-induced ARF decreased the
      expressions of water channel AQP 2, 3 and sodium potassium pump Na,K-ATPase in
      the renal medulla. However, administration of ACC markedly incremented AQP 2, 3
      and Na,K-ATPase expressions. Therefore, these data indicate that administration
      of ACC ameliorates regulation of the urine concentration and renal functions in
      rats with ischemia/reperfusion-induced ARF.

PMID- 21905281
TI  - Ameliorative effects of ethanolic leaf extract of Azadirachta indica on renal
      histologic alterations in streptozotocin-induced diabetic rats.
AB  - We studied the effect of ethanolic leaf extract of Azadirachta indica (AIE) on
      the microanatomy of the kidney of streptozotocin-induced diabetic rats. Thirty
      male Wistar rats (161-190 g) were randomly assigned to one of five treatment
      groups of six animals each: control, diabetic, diabetic + AIE, diabetic +
      metformin, AIE only. Diabetes was induced with a single intraperitoneal dose of
      streptozotocin (70 mg/kg body weight). AIE and metformin were administered orally
      for 50 days (50 d) at 500 mg/kg bw/d and 350 mg/kg bw/d, respectively. Blood
      glucose was estimated by glucose oxidase method; plasma urea and creatinine were
      assayed; and paraffin sections of the kidney were stained by periodic acid-Schiff
      technique. Untreated diabetic rats exhibited marked hyperglycemia. Renal
      histopathology of these animals showed features of diabetic nephropathy, with
      nodular glomerulosclerosis and vacuolation of proximal tubule cells (Armanni
      Ebstein phenomenon). These feature were absent in the diabetic rats treated with
      AIE. Besides, plasma urea and creatinine were not significantly different from
      the control in this group (p > 0.05), in contrast to the untreated diabetic rats,
      where significant increases in these markers (p < 0.05). These findings showed
      that the leaf extract of Azadirachta indica ameliorates hyperglycemia and
      diabetic nephropathy in rats.

PMID- 21905282
TI  - SuHeXiang Wan essential oil alleviates amyloid beta induced memory impairment
      through inhibition of tau protein phosphorylation in mice.
AB  - SuHeXiang Wan (SHXW), a traditional Chinese medicine, has been used orally for
      the treatment of seizures, infantile convulsions and stroke. Previously, we
      reported the effects of a modified SHXW essential oil in terms of sedative
      effect, anticonvulsant activity and antioxidative activity. The purpose of this
      study was to evaluate the potential beneficial effects of SHXW essential oil in
      neurodegenerative diseases such as Alzheimer's disease (AD). SHXW essential oil
      was extracted from nine herbs. The mouse AD model was induced by a single
      injection of amyloid beta protein (Abeta(1-42)) into the hippocampus. The animals
      were divided into four groups, the negative control group injected with Abeta(42
      1), the Abeta group injected with Abeta(1-42), the SHXW group inhaled SHXW
      essential oil and received Abeta(1-42) injection, and the positive control group
      administered with docosahexaenoic acid (DHA, 10 mg/kg) and with subsequent
      Abeta(1-42) injection. Mice were analyzed by behavioral tests and immunological
      examination in the hippocampus. An additional in vitro investigation was
      performed to examine whether SHXW essential oil inhibits Abeta(1-42) induced
      neurotoxicity in a human neuroblastoma cell line, SH-SY5Y cells. Pre-inhalation
      of SHXW essential oil improved the Abeta(1-42) induced memory impairment and
      suppressed Abeta(1-42) induced JNK, p38 and Tau phosphorylation in the
      hippocampus. SHXW essential oil suppressed Abeta-induced apoptosis and ROS
      production via an up-regulation of HO-1 and Nrf2 expression in SH-SY5Y cells. The
      present study suggests that SHXW essential oil may have potential as a
      therapeutic inhalation drug for the prevention and treatment of AD.

PMID- 21905283
TI  - Matrine suppresses production of IL-23/IL-17 and ameliorates experimental
      autoimmune encephalomyelitis.
AB  - Matrine (MAT), a quinolizidine alkaloid derived from the herb Radix Sophorae
      Flave, has been suggested to possess immunomodulatory characteristics; however,
      whether it is effective in multiple sclerosis (MS), an autoimmune disease of the
      central nervous system (CNS), is not known. Our aim was to bridge this gap by
      investigating the possible therapeutic effects of MAT on experimental autoimmune
      encephalomyelitis (EAE), an animal model of MS. We have found that, compared to
      the untreated controls, MAT-treated rats showed a significant decrease in
      clinical scores, in CNS infiltration of inflammatory cells (including CD4(+),
      CD8(+) T cells and macrophages) and demyelination. Furthermore, serum levels of
      IL-23 and IL-17 showed a marked reduction after MAT treatment, particularly in
      rats treated with higher doses of MAT. This study demonstrates that
      administration of MAT, as a natural compound, might be a novel therapy for
      autoimmune disorders such as MS.

PMID- 21905284
TI  - Anti-inflammatory effects of Scoparia dulcis L. and betulinic acid.
AB  - The aims of this study intended to investigate the anti-inflammatory activity of
      the 70% ethanol extract from Scoparia dulcis (SDE) and betulinic acid on lambda
      carrageenan-induced paw edema in mice. The anti-inflammatory mechanism of SDE and
      betulinic acid was examined by detecting the levels of cyclooxygenase-2 (COX-2),
      nitric oxide (NO), tumor necrosis factor (TNF-alpha), interleukin-1beta (IL
      1beta) and malondialdehyde (MDA) in the edema paw tissue and the activities of
      superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione
      reductase (GRd) in the liver. The betulinic acid content in SDE was detected by
      high performance liquid chromatography (HPLC). In the anti-inflammatory model,
      the results showed that SDE (0.5 and 1.0 g/kg) and betulinic acid (20 and 40
      mg/kg) reduced the paw edema at 3, 4 and 5 h after lambda-carrageenan
      administration. Moreover, SDE and betulinic acid affected the levels of COX-2,
      NO, TNF-alpha and IL1-beta in the lambda-carrageenan-induced edema paws. The
      activities of SOD, GPx and GRd in the liver tissue were increased and the MDA
      levels in the edema paws were decreased. It is suggested that SDE and betulinic
      acid possessed anti-inflammatory activities and the anti-inflammatory mechanisms
      appear to be related to the reduction of the levels of COX-2, NO, TNF-alpha and
      IL1-beta in inflamed tissues, as well as the inhibition of MDA level via
      increasing the activities of SOD, GPx and GRd. The analytical result showed that
      the content of betulinic acid in SDE was 6.25 mg/g extract.

PMID- 21905286
TI  - Gingko biloba extract (EGb 761) attenuates the focal cerebral ischemic injury
      induced decrease in astrocytic phosphoprotein PEA-15 levels.
AB  - EGb 761 is an extract of Gingko biloba that is neuroprotective against focal
      cerebral ischemic injury. PEA-15 (phosphoprotein enriched in astrocytes 15)
      modulates cell proliferation and apoptosis. In this study, we investigated
      whether EGb 761 regulates the expression of PEA-15 and two phosphorylated forms
      of PEA-15 (Ser 104 and Ser 116) in middle cerebral artery occlusion (MCAO)
      induced injury. Adult male rats were treated with vehicle or EGb 761 (100 mg/kg)
      prior to MCAO and cerebral cortices were collected 24 h after MCAO. A reduction
      in expression of PEA-15 and its phosphorylated forms induced by MCAO injury was
      detected using a proteomic approach. EGb 761 pretreatment prevented the ischemic
      injury-induced decrease in PEA-15 expression. Western blot analysis demonstrated
      that EGb 761 attenuates the injury-induced reduction in PEA-15, phospho-PEA-15
      (Ser 104), phospho-PEA-15 (Ser 116). Phosphorylation of PEA-15 influences its
      anti-apoptotic function; a decrease in PEA-15 phosphorylation induces apoptotic
      cell death. The maintenance of PEA-15 phosphorylation by EGb 761 pretreatment
      during cerebral ischemic injury indicates that EGb 761 is a neuroprotective
      against cerebral ischemic injury.

PMID- 21905285
TI  - Oldenlandia diffusa Ameliorates Dextran Sulphate Sodium-Induced Colitis Through
      Inhibition of NF-kappaB Activation.
AB  - Ulcerative colitis (UC) is an inflammatory bowel disease, which is a chronic
      gastrointestinal disorder. Oldenlandia diffusa (OD) has been used as a
      traditional oriental medicine for inflammation. However, the regulatory effect
      and molecular mechanism of OD in intestinal inflammation are not yet understood.
      This study investigated the protective effect of OD in dextran sulfate sodium
      (DSS)-induced colitis. Mice treated with DSS showed remarkable clinical signs,
      including weight loss, and reduced colon length. Administration of OD attenuated
      these signs and significantly suppressed levels of interleukin (IL)-6, IL-1beta
      and expression of cyclooxygenase-2 in DSS-treated colon tissues. OD also reduced
      the activation of transcription nuclear factor-kappaB p65 in DSS-treated colon
      tissues. Hentriacontane, a constituent of OD, attenuated weight loss, colon
      shortening, and levels of IL-6 caused by DSS. Taken together, the results provide
      experimental evidence that OD might be a useful therapeutic medicine for patients
      with UC.

PMID- 21905287
TI  - Evidence for improved neuropharmacological efficacy and decreased neurotoxicity
      in mice with traditional processing of Rhizoma Arisaematis.
AB  - Rhizoma Arisaematis (RA, the rhizome of Pinellia pedatisecta Schott) is a
      traditional Chinese medicine commonly used in the treatment of convulsions,
      inflammation, and cancer. Despite the fact that it has been used for more than
      2000 years, the pharmacological and toxic effects of traditionally processed
      products of RA are still unclear. In this study, we attempted to investigate the
      effects exerted by untreated crude RA and different preparations of RA treated
      with alumen in combination with ginger juice (Zhinanxing) or bile juice
      (Dannanxing) in ICR mice. The results showed that both the Zhinanxing and
      Dannanxing water extracts exerted significantly increased sedative effects, as
      indicated by the inhibitory effects on ambulatory distances, jumps, vertical
      plane entries, and prolonged pentobarbital-induced sleeping time. The extracts
      also exerted significantly increased analgesic effects (increase of tail flick
      latency in nociceptive testing) in mice than did the unprocessed crude RA after
      oral administration for one to three days, and effects persisted 18 days after
      the cessation of treatment. By contrast, the toxic effects, such as an increase
      in stereotype-1 episodes of locomotor activities and reduction of the retention
      time on a rotating rod (motor equilibrium dysfunction), were observed only in
      mice treated with the unprocessed crude RA for three consecutive days, and
      effects persisted for 18 days after the cessation of treatment. These neurotoxic
      effects were accompanied by an increase in plasma lipid peroxidation (LPO),
      decrease in whole blood nitric oxide (NO(x)) levels, and inhibition of Na(+)/K(+)
      ATPase activities in membrane fractions of erythrocytes and in the cerebral
      cortex. In conclusion, these findings provide scientific evidence that the
      processed RA indeed possesses not only enhanced neuropharmacological efficacy but
      also reduced neurotoxic effects as compared to the unprocessed crude RA. The
      signaling of NO(x)/oxidative stress/Na(+)-K(+)- ATPase activities played a role,
      at least in part, in the underlying mechanisms of neurotoxic effects induced by
      the crude RA.

PMID- 21905288
TI  - Effects of Panax notoginseng saponins on proliferation and differentiation of rat
      hippocampal neural stem cells.
AB  - We aimed to investigate the effects of Panax notoginseng saponins (PNS) on
      proliferation, differentiation and self-renewal of rat hippocampal neural stem
      cells (NSCs) in vitro. Rat hippocampal NSCs were isolated from post-natal day 1
      (P1) rats and cultured in a serum-free medium. The neurospheres were identified
      by the expressions of nestin, class III beta-tublin (Tuj-1) and glial fibrillary
      acid protein (GFAP). The cells were given PNS and subjected to oxygen glucose
      deprivation (OGD) as an in vitro model of brain ischemia reperfusion. The
      proliferation of NSCs was determined by MTT colorimetry, nestin/BrdU
      immunofluorescent double-labeling and RT-PCR. Differentiation of NSCs was
      assessed by immunofluorescent double-labeling of nestin/BrdU, nestin/vimentin,
      and nestin/Tuj-1. The primary cells and the first two passages of cells formed
      certain amount of neurospheres, the cells derived from a single cell clone also
      formed neurospheres. Nestin, BrdU, GFAP and Tuj-1-positive cells appeared in
      those neurospheres. Compared to the control group, PNS significantly promoted NSC
      proliferation and the expression of nestin/BrdU, and also enhanced Tuj-1,
      vimentin, and nestin mRNA expressions in hippocampal NSCs. PNS significantly
      increased area density, optical density and numbers of nestin/BrdU,
      nestin/vimentin, and nestin/Tuj-1 positive cells following OGD. These results
      indicate that PNS can promote proliferation and differentiation of hippocampus
      NCSs in vitro after OGD, suggesting its potential benefits on neurogenesis and
      neuroregeneration in brain ischemic injury.

PMID- 21905289
TI  - Inhibitory effect of pomegranate on intestinal sodium dependent glucose uptake.
AB  - Intestinal glucose uptake is mainly performed by its specific transporters, SGLT1
      and GLUTs expressed in the intestinal epithelial cells. By using Caco-2 cells and
      2-NBDG, we observed that intestinal glucose uptake was markedly inhibited by
      pomegranate (Punica granatum L, PG) among 200 screened edible Korean plants. The
      effects of the PG extract on Na(+)-dependent glucose uptake were further
      evaluated using brush border membrane vesicles (BBMV) obtained from the mouse
      small intestine. PG inhibited Na(+)-dependent glucose uptake with the IC(50)
      value of 424 MUg/ml. The SGLT1 protein expression was dose dependently down
      regulated with PG treatment in Caco-2 cells. We next assessed the
      antihyperglycemic effect of PG in streptozotocin (STZ)-induced diabetic mice.
      Administration of PG (800 mg/kg) to STZ mice for four weeks improved postprandial
      glucose regulation. Furthermore, elevated Na(+)-dependent glucose uptake by BBMV
      isolated from STZ mice was normalized by PG treratment. These results suggest
      that PG could play a role in controlling the dietary glucose absorption at the
      intestinal tract by decreasing SGLT1 expression, and may contribute to blood
      glucose homeostasis in the diabetic condition.

PMID- 21905290
TI  - Comparative chemical and statistical analysis of cultivated and wild Radix
      Scutellariae.
AB  - Radix Scutellariae has been widely used to hasten the process of heat clearing
      and dampness drying in traditional Chinese medicine. The resource of wild Radix
      Scutellariae is scarce; an increasing amount of cultivated Radix Scutellariae has
      become available in the market. To determine the clinical effects of Radix
      Scutellariae, we conducted a comparative analysis of the chemical compositions of
      cultivated and wild Radix Scutellariae. An HPLC fingerprint method was developed
      to determine simultaneously the amounts of baicalin, baicalein, and wogonin,
      which have been identified as active compounds in Radix Scutellariae. Chinese
      pharmacopoeia methodology was also applied to measure the ethanolic extract
      content of the wild and cultivated samples. Although the cultivated and wild
      Radix Scutellariae have similar concentrations of baicalein and wogonin, the
      concentrations of baicalin and ethanolic extracts are higher in the cultivated
      samples (i.e., 15.14% +/- 1.11% and 56.90% +/- 2.83%, respectively, compared to
      11.17% +/- 1.11%, and 44.16% +/- 2.02%, respectively, in the wild Radix
      Scutellariae). Data from fingerprint analysis were statistically analyzed using
      the decision tree and hierarchical cluster methods. The study was carried out
      with 58 samples. Thus, the current study provides significant guidelines for
      distinguishing cultivated and wild Radix Scutellariae.

PMID- 21905291
TI  - Simultaneous determination of ten active components in 12 Chinese Piper species
      by HPLC.
AB  - Piper is a genus that is recently valued for the treatment of central nervous
      system diseases. The major constituents, amides and lignans, are responsible for
      the antinociceptive and antidepressant activities. This study developed a RP-HPLC
      UV method for the simultaneous determination of eight amides and two lignans in
      twelve different species of Piper. HPLC separation was accomplished on a C18
      analytical column (5 MUm, 250 mm * 4.6 mm, i.d.) with a gradient mobile phase
      consisting of acetonitrile and water at a flow rate of 1.0 ml/min. All the
      calibration curves showed good linear correlation coefficients (r > 0.9997) over
      the test ranges. The relative standard deviation of the current method was less
      than 2.90% for intra- and inter-day assays and the average recoveries were
      between 98.25% and 103.08%. The HPLC method established is appropriate for
      quality control purposes and allows for the differentiation of Piper species.

PMID- 21905292
TI  - Causes of abortion in Scottish sheep flocks in 2011.

PMID- 21905293
TI  - Proceedings of the 36th Congress of the Societe de Biomecanique. August 31
      September 2, 2011. Besancon, France.

PMID- 21905294
TI  - Abstracts of EuroSpine 2011. October 19-21, 2011. Milan, Italy.

PMID- 21905295
TI  - Abstracts of ESICM LIVES 2011, the 24th Annual Congress of the European Society
      of Intensive Care Medicine. October 1-5, 2011. Berlin Germany.

PMID- 21905296
TI  - A disarticulating spinal lesion. Bacterial abscess.

PMID- 21905298
TI  - Abstracts of the 15th Congress of the European Federation of Neurological
      Societies (EFNS). September 11-13, 2011. Budapest, Hungary.

PMID- 21905297
TI  - Giant intraventricular mass arising from the septum pellucidum. Cavernoma.

PMID- 21905299
TI  - [Abstracts of the 84th Annual Meeting of the Northern German Dermatological
      Society. August 26-28, 2011. Magdebury, Germany].

PMID- 21905300
TI  - Academia: Small-school science.

PMID- 21905301
TI  - Abstracts of the 96th National Congress of the Italian Society of Orthopaedics
      and Traumatology. Rimini, Italy. October 1-5, 2011.

PMID- 21905302
TI  - Interview. Laurent Keller.

PMID- 21905303
TI  - Valuing nature.

PMID- 21905304
TI  - Alzheimer's association update July 2011.

PMID- 21905306
TI  - Biological safety of nasal thallium-201 administration: a preclinical study for
      olfacto-scintigraphy.

PMID- 21905305
TI  - Intercellular communication amplifies stressful effects in high-charge, high
      energy (HZE) particle-irradiated human cells.

PMID- 21905307
TI  - Gene expression associated with DNA-dependent protein kinase activity under
      normoxia, hypoxia, and reoxygenation.

PMID- 21905308
TI  - Association between skin phototype and radiation dermatitis in patients with
      breast cancer treated with breast-conserving therapy: suntan reaction could be a
      good predictor for radiation pigmentation.

PMID- 21905309
TI  - Effect of dose fractionation on pulmonary complications during total body
      irradiation.

PMID- 21905310
TI  - Radiation therapy in patients with implanted cardiac pacemakers and implantable
      cardioverter defibrillators: a prospective survey in Japan.

PMID- 21905311
TI  - Prediction of local failures with a combination of pretreatment tumor volume and
      apparent diffusion coefficient in patients treated with definitive radiotherapy
      for hypopharyngeal or oropharyngeal squamous cell carcinoma.

PMID- 21905312
TI  - SunMed,  LLC, bougies.

PMID- 21905313
TI  - A call to action.

PMID- 21905314
TI  - Acute medicine--an alternative take.

PMID- 21905315
TI  - Acute medicine--an alternative take.

PMID- 21905316
TI  - A patient with recurrent oedema of the hands and a collapse.

PMID- 21905317
TI  - What reductions in dependency cost result from treatment in an inpatient
      neurological rehabilitation unit for people with stroke?

PMID- 21905318
TI  - The need for dedicated dermatology beds.

PMID- 21905319
TI  - Emergency visits after recent percutaneous coronary intervention.

PMID- 21905321
TI  - Abstracts of the 15th Congress of the European Society for Organ Transplantation
      & 22nd Annual Conference of the British Society for Histocompatibility &
      Immunogenetics. September 4-7, 2011. Glasgow, United Kingdom.

PMID- 21905322
TI  - "Mr. Burk is most interested in their welfare": J.G. Burk's campaign to help the
      Anishinabeg of northwestern Ontario, 1923-53.
AB  - Although there is a small but growing body of literature on Euro-Canadians who
      acted "with good intentions" towards the First Nations (Haig-Brown and Nock
      2006), precious little has been written about those within the ranks of the
      Department of Indian Affairs who acted benevolently towards the Aboriginal
      peoples. James Gerry Burk, Indian agent for the Anishinabeg of the western Lake
      Superior region for three decades (1923-53), was one such individual. He chose to
      ignore the department's prevailing racist ideology in favour of nurturing the
      incipient desire for industry and enterprise that he saw first-hand among the
      Aboriginal constituents of his agency. In the process, he was compelled to
      overcome numerous obstacles that Indian Affairs placed in his way. As a result,
      Burk's career stands as a glowing testament to the indomitable spirit of one
      departmental official's commitment to assisting the Aboriginal peoples.

PMID- 21905320
TI  - [Special report on vaccination week: measles, April No. 4/2011 1].

PMID- 21905323
TI  - Enduring pictures in our heads: the continuance of authoritarianism and racial
      stereotyping.
AB  - This study highlights the importance of examining the influence of personality
      measures, specifically authoritarianism, on negative racial stereotyping, even in
      an era of alleged color blindness. The authors examine the relationship of
      various demographic variables and authoritarianism with negative racial
      stereotyping in a sample of White urban respondents. Current literature suggests
      that age, sex, marital status, religious identification, religious service
      attendance, education level, income, political affiliation, level of
      authoritarianism, and the demographic composition in an individual's local
      population all affect racial stereotyping. The evidence presented, using path
      analysis, suggests that some demographic characteristics influence the level of
      negative racial stereotyping. While the effects of most included demographic
      characteristics were statistically significant, others, which continually
      resurface in the literature, remained insignificant (such as the demographic
      composition of the respondent's area). The results of this study challenge the
      loss of traditional prejudice with color blindness and point to the importance of
      authoritarianism as a mediating factor in negative racial stereotyping. The
      authors conclude the greatest indicators of negative racial stereotyping included
      in this study are authoritarianism, education, and income, while many other
      demographics - such as marital status, religious identification and attendance,
      and political affiliation - have indirect influences through authoritarianism.

PMID- 21905324
TI  - Examining the long-term racial disparities in health and economic conditions
      among Hurricane Katrina survivors: policy implications for Gulf Coast recovery.
AB  - This study examines disparities in the long-term health, emotional well-being,
      and economic consequences of the 2005 Gulf Coast hurricanes. Researchers analyzed
      the responses of 216 Black and 508 White Hurricane Katrina survivors who
      participated in the ABC News Hurricane Katrina Anniversary Poll in 2006. Self
      reported data of the long-term negative impact of the hurricane on personal
      health, emotional well-being, and finances were regressed on race, income, and
      measures of loss, injury, family mortality, anxiety, and confidence in the
      government. Descriptive analyses, stepwise logistic regression, and analyses of
      variance revealed that Black hurricane survivors more frequently reported
      hurricane-related problems with personal health, emotional well-being, and
      finances. In addition, Blacks were more likely than Whites to report the loss of
      friends, relatives, and personal property.

PMID- 21905325
TI  - South Africans and Mexicans in Florida: intergroup conflict.
AB  - Newly arriving immigrants from Southern Africa and Mexicans do not get on well in
      the sunbelt state of Florida. A persistent theme emerging from discussions with
      South Africans on their relationship with Mexicans is that both sides perceive
      the other as culturally ethnocentric. The antagonistic relationship between both
      social groups is due to strong ethnic bonds and the clash of cultures.

PMID- 21905326
TI  - African American students' reactions to Benjamin Cooke's "Nonverbal Communication
      Among Afro-Americans: An Initial Classification".
AB  - The nonverbal communication behavior of Black people continues to take new forms
      as time progresses. In Kochman's 1972 book, Rappin' and Stylin' Out:
      Communication in Urban Black America, Benjamin Cooke introduced an initial
      classification and code of nonverbal behaviors among people of African descent.
      In this study, students react to Cooke's study conducted in the late 1960s by
      commenting on Cooke's initial findings in comparison to nonverbal behaviors
      practiced among Black people as of late. Respondents suggest that while
      differences and variations exist between the expression of nonverbal behaviors
      exhibited by the original group studied and people recently observed, there yet
      remains a similarity in the cultural significance and motivation behind the
      displays.

PMID- 21905327
TI  - Between black and brown: blaxican (black-Mexican) multiracial identity in
      California.
AB  - This article explores the racial/ethnic identities of multiracial Black-Mexicans
      or "Blaxicans." In-depth interviews with 12 Blaxican individuals in California
      reveal how they negotiate distinct cultural systems to accomplish multiracial
      identities. I argue that choosing, accomplishing, and asserting a Blaxican
      identity challenges the dominant monoracial discourse in the United States, in
      particular among African American and Chicana/o communities. That is, Blaxican
      respondents are held accountable by African Americans and Chicanas/os/Mexicans to
      monoracial notions of "authenticity." The process whereby Blaxicans move between
      these monoracial spaces to create multiracial identities illustrates crucial
      aspects of the social construction of race/ethnicity in the United States and the
      influence of social interactions in shaping how Blaxicans develop their
      multiracial identities.

PMID- 21905330
TI  - A response to Bugeja, Clapperton, Killian, Stephan and Ozanne-Smith.

PMID- 21905331
TI  - Geographical information systems: an effective planning and decision-making
      platform for community health coalitions in Australia.
AB  - The development of locally-based healthcare initiatives, such as community health
      coalitions that focus on capacity building programs and multi-faceted responses
      to long-term health problems, have become an increasingly important part of the
      public health landscape. As a result of their complexity and the level of
      investment, it has become necessary to develop innovative ways to help manage
      these new healthcare approaches. Geographical Information Systems (GIS) have been
      suggested as one of the innovative approaches that will allow community health
      coalitions to better manage and plan their activities. The focus of this paper is
      to provide a commentary on the use of GIS as a tool for community coalitions and
      discuss some of the potential benefits and issues surrounding the development of
      these tools.

PMID- 21905332
TI  - Per diem payments for the care provided to eligible veterans evacuated from a
      state home as a result of an emergency. Final rule.
AB  - The Department of Veterans Affairs (VA) amends its regulations concerning per
      diem payments to States to permit continuation of such payments in some
      situations for veterans who have been evacuated from a State home as a result of
      an emergency. Per diem is the daily rate paid by VA to a State for providing a
      specified level of care to eligible veterans in a facility that is officially
      recognized and certified by VA. This final rule authorizes VA to continue to pay
      per diem when veterans for whom VA is paying per diem are evacuated as a result
      of an emergency from a State home to a facility that is not recognized by VA as a
      State home. The rule requires, in order for per diem payments to continue while
      the veteran is relocated due to an emergency, that an appropriate VA official
      determine whether an emergency exists and whether the facility to which veterans
      may be evacuated (evacuation facility) complies with certain minimum standards.
      The rule establishes the minimum standards that facilities to which veterans are
      evacuated must meet in order for States to continue receiving per diem for
      relocated veterans. These standards also apply to evacuation facilities when
      veterans are evacuated from contract nursing homes.

PMID- 21905333
TI  - [Treatment of chronic migraine].

PMID- 21905334
TI  - [Risk factors, features of clinical course and treatment approaches in aged
      patients with cerebral stroke].

PMID- 21905335
TI  - [Chronobiology of depression: a role of suprachiasmatic nuclei of the
      hypothalamus and clock genes].

PMID- 21905336
TI  - [The quantitative characteristics of alcoholism course: the order of disease
      trait appearance].

PMID- 21905337
TI  - [Prevalence of sleep disorders in citizens of Chuvash Republic (results from
      complete interview study)].

PMID- 21905338
TI  - [Adaptol in the treatment of chronic cervicogenic headache].

PMID- 21905339
TI  - [Pharmacologic neuroprotection of the brain in carotid artery surgeries].

PMID- 21905340
TI  - [Cognitive disorders in patients with chronic heart failure].

PMID- 21905341
TI  - [Thalamic dementia].

PMID- 21905342
TI  - [Psychotic disorders in Parkinson's disease and dementia with Lewy bodies].

PMID- 21905343
TI  - [Diagnosis and treatment of multiple sclerosis].

PMID- 21905344
TI  - [Clinical characteristics and treatment of depersonalization disorders].

PMID- 21905345
TI  - [12th Annual Congress of the Croatian Rheumatologic Society HLA-a. Zadar, 14-17
      October 2010].

PMID- 21905346
TI  - Summary health statistics for U.S. adults: National Health Interview Survey,
      2009.
AB  - OBJECTIVES: This report presents health statistics from the 2009 National Health
      Interview Survey (NHIS) for the civilian noninstitutionalized adult population,
      classified by sex, age, race and ethnicity, education, family income, poverty
      status, health insurance coverage, marital status, and place and region of
      residence. Estimates are presented for selected chronic conditions and mental
      health characteristics, functional limitations, health status, health behaviors,
      health care access and utilization, and human immunodeficiency virus testing.
      Percentages and percent distributions are presented in both age-adjusted and
      unadjusted versions. DATA SOURCE: NHIS is a household, multistage probability
      sample survey conducted annually by interviewers of the U.S. Census Bureau for
      the Centers for Disease Control and Prevention's National Center for Health
      Statistics. In 2009, data were collected on 27,731 adults in the Sample Adult
      questionnaire. The conditional response rate was 80.1%, and the final response
      rate was 65.4%. The health information for adults in this report was obtained
      from one randomly selected adult per family. In very rare instances where the
      sample adult was not able to respond for himself or herself, a proxy was used.
      HIGHLIGHTS: In 2009, 61% of adults aged 18 years and over reported excellent or
      very good health. Fifty-five percent of adults had never participated in any type
      of vigorous leisure-time physical activity, and 17% of adults did not have a
      usual place of health care. Twelve percent of adults had been told by a doctor or
      health professional that they had heart disease, and 24% had been told on two or
      more visits that they had hypertension. Twenty-one percent of all adults were
      current smokers, and 21% were former smokers. Based on estimates of body mass
      index, 35% of adults were overweight, and 27% were obese.

PMID- 21905347
TI  - Introducing 'technique tips'.

PMID- 21905348
TI  - Technique tips--a simple and aesthetic way to intrude upper incisors.

PMID- 21905349
TI  - Recurrent intra-oral herpes simplex 1 infection.
AB  - Human herpes simplex 1 virus (HSV-1) is a DNA virus that has the ability to lie
      latent and be subsequently re-activated at any point during a patient's life. In
      the immunocompetent patient, resolution of clinical signs and symptoms usually
      occurs spontaneously after 14 days. In the immunocompromised patient, healing is
      often delayed and the effects are much more debilitating. Indications for
      therapeutic regimes of systemic antiviral treatment are discussed. CLINICAL
      RELEVANCE: Recurrent oral ulceration caused by HSV-1 may be seen by the general
      dental practitioner and can cause significant morbidity.

PMID- 21905350
TI  - Caries and the older patient.
AB  - Ageing of the population, together with prolonged retention of teeth, has brought
      new challenges to dentistry. Whereas in the past oral care for the elderly was
      restricted to provision of dentures, older patients are now presenting with
      dental caries and failed restorations. These problems may have an impact on their
      general health and quality of life. Poor oral hygiene, xerostomia and diet are
      among the risk factors for caries in older patients and need to be addressed in
      order to achieve control of the disease. Carious lesions can be treated
      conservatively in many cases or may need surgical management. CLINICAL RELEVANCE:
      Caries is an oral health issue among older patients and can result in tooth loss.
      Oral health has a great impact on general health and quality of life of elderly
      people.

PMID- 21905351
TI  - Treatment options for the free end saddle.
AB  - Many treatment options are available for the management of the free end saddle.
      This paper reviews past and current treatment methods for management of this
      situation. CLINICAL RELEVANCE: To understand the problem posed by the free end
      saddle and the techniques available to clinicians for its management in general
      dental practice.

PMID- 21905352
TI  - Lingual orthodontics: an overview.
AB  - As adults increasingly seek orthodontic treatment, a growth has been witnessed in
      the demand for aesthetic orthodontics, the ultimate of which are appliances
      bonded to the lingual surfaces of the teeth. Development has spanned 30 years and
      many of the initial challenges faced with this approach have now been overcome.
      An overview is provided on the development of lingual appliances from conception
      through to the current systems available. Lingual orthodontics is not for every
      patient seeking treatment and therefore the indications and contra-indications
      are discussed, together with the advantages and disadvantages of this
      increasingly popular approach. CLINICAL RELEVANCE: Patients are increasingly
      asking dental professional about lingual appliances.

PMID- 21905353
TI  - Differential diagnosis for orofacial pain, including sinusitis, TMD, trigeminal
      neuralgia.
AB  - Correct diagnosis is the key to managing facial pain of non-dental origin. Acute
      and chronic facial pain must be differentiated and it is widely accepted that
      chronic pain refers to pain of 3 months or greater duration. Differentiating the
      many causes of facial pain can be difficult for busy practitioners, but a logical
      approach can be beneficial and lead to more rapid diagnoses with effective
      management. Confirming a diagnosis involves a process of history-taking, clinical
      examination, appropriate investigations and, at times, response to various
      therapies. CLINICAL RELEVANCE: Although primary care clinicians would not be
      expected to diagnose rare pain conditions, such as trigeminal autonomic
      cephalalgias, they should be able to assess the presenting pain complaint to such
      an extent that, if required, an appropriate referral to secondary or tertiary
      care can be expedited. The underlying causes of pain of non-dental origin can be
      complex and management of pain often requires a multidisciplinary approach.

PMID- 21905354
TI  - Allergy to local anaesthetic agents used in dentistry--what are the signs,
      symptoms, alternative diagnoses and management options?
AB  - This paper addresses the signs and symptoms of local anaesthetic
      hypersensitivity, differential diagnoses and the management of a patient with
      suspected allergy to local anaesthetics. CLINICAL RELEVANCE: While allergy to
      anaesthetic is rare, knowledge of other causes of similar symptoms is important.

PMID- 21905355
TI  - Fabrication of an auricular prosthesis: a case report.
AB  - The fabrication of ear prosthesis is considered by many prosthetists to be one of
      the more difficult replacements in maxillofacial reconstruction. The severe
      undercuts and pronounced convolutions of the ear's surface present a challenge in
      simulating a natural proportioned prosthesis. The mould for the ear is generally
      made by creating a three surface die to reproduce the unique configuration
      adequately and to allow retrieval of the finished prosthesis without damage. This
      article presents an outlined procedure in the basic fabrication of a prosthetic
      ear by a conventional technique where the wax pattern is fabricated from the
      impression of an individual with a similarly proportioned ear. CLINICAL
      RELEVANCE: Fabricating an auricular prosthesis may be part of the work of a
      maxillofacial department.

PMID- 21905356
TI  - Personal development plans (in primary dental care)--getting started.
AB  - This article reviews how to develop a personal development plan, its benefits and
      how it may relate to the GDC's proposed revalidation scheme. CLINICAL RELEVANCE:
      Revalidation is an essential part of reassuring the public that the profession
      delivers care to appropriate standards in safe work environments. A personal
      development plan is a key element in improving performance and quality of care.

PMID- 21905357
TI  - The use of adhesive materials in gingival aesthetics.

PMID- 21905358
TI  - Optimizing impressioning?

PMID- 21905359
TI  - Oral cancer: comprehending the condition, causes, controversies, control and
      consequences. 8. Communicating about cancer.

PMID- 21905360
TI  - Physical signs for the General Dental Practitioner. Case 86. Ascites.

PMID- 21905361
TI  - Changes in the field of endodontics.

PMID- 21905362
TI  - Endodontic prognosis assessment.
AB  - There are several variables which must be considered before initiating endodontic
      treatment, including assessing the feasibility of endodontic treatment,
      addressing past, present and future periodontal concerns, determining the
      restorability of the tooth, and detecting root fractures. If these parameters are
      not carefully evaluated, then short- or long-term endodontic success may be
      questionable. Endodontic prognosis assessment is often subjective, based on
      objective finding, but ultimately determined by the experience of the operator.
      Although dentists must rely upon evidence-based research to determine the best
      modality of treatment, good clinical judgment and experience may override the
      most objective findings. This article discusses the objective and subjective
      criteria which must be evaluated for determining the potential prognosis of
      endodontic treatment.

PMID- 21905363
TI  - Irrigation in endodontic treatment.
AB  - The primary endodontic treatment goal is to optimize root canal disinfection and
      to prevent reinfection. Successful root canal therapy relies on the combination
      of proper instrumentation, irrigation, and obturation of the root canal system.
      In this review of the literature, various irrigants and the interactions between
      irrigants are discussed and new delivery systems are introduced.

PMID- 21905364
TI  - Endoscopy in endodontics.
AB  - A successful outcome of endodontic treatment depends to a large extent on
      accurate intraoperative findings. Conventionally, micromirrors and microprobes
      have been used for this purpose. The dental operating microscope (DOM) has been
      implemented to enhance visibility during dental procedures. However, the
      microscope, a sizable tool, remains between operating field and the dental
      practitioner, making his ability to manipulate more complicated. Also, the
      interference of the hands and the handpiece with the visualization of the
      surgical field and inaccurate observation of the endodontic instruments during
      the procedure. Endoscopy reportedly provides the dentist with excellent vision
      and ease of use. It also provides a better intraoperative visualization in
      comparison with micromirrors. Further development of endoscopy made it possible
      to combine magnification, light, irrigation/suction and surgical microinstruments
      in one device. This combination could lead to an advanced root canal treatment
      technique.

PMID- 21905365
TI  - From files to SAF: 3D endodontic treatment is possible at last.
AB  - 3D cleaning, shaping and obturation of root canals has always been the desired
      goal of endodontic treatment which in many cases is difficult to attain. The
      introduction of NiTi rotary files made a major change in endodontic practice,
      making treatment easier, safer and faster. Nevertheless, after 16 years of
      intensive development, most of these instruments still share several drawbacks,
      the major one being the inability to three-dimensionally clean and shape oval
      root canals. The Self-Adjusting File (SAF) System was designed to overcome many
      of the current drawbacks of rotary file systems. It is based on a hollow, highly
      compressible file that adapts itself three-dimensionally to the shape of a given
      root canal, including its cross section. The file is operated with vibratory in
      and-out motion, with continuous irrigation delivered by a peristaltic pump
      through the hollow file. A uniform layer of dentin is removed from the whole
      circumference of the root canal, thus achieving the main goals of root canal
      treatment while preserving the remaining root dentin. The 3D scrubbing effect of
      the file, combined with the always fresh irrigant, result in unprecedentedly
      clean canals which facilitate in turn better obturation. More effective
      disinfection of flat-oval root canals is another goal which is simultaneously
      attained. The safety of the root-canal treatment is also greatly enhanced by the
      high mechanical stability of the SAF and by using a new concept of no-pressure
      irrigation. The SAF System gets the operator much closer to the long-desired goal
      of 3D root-canal treatment.

PMID- 21905366
TI  - The coming era of regenerative endodontics: what an endodontist needs to know.
AB  - Recently, two new clinical concepts have emerged for the management of
      endodontically compromised immature permanent teeth. One involves a
      revitalization approach to achieve tissue generation and regeneration in the root
      canal system. In this method, new living tissue is expected to form in the
      cleaned canal space allowing continued root development in terms of both length
      and thickness. The other is the active pursuit of pulp/dentine regeneration via
      tissue engineering technology to implant or re-grow pulps. Although the
      technology is still at its infancy, it has potential to benefit immature pulpless
      teeth by allowing continued growth and maturation. Evidence has shown that using
      dental stem cells, pulp and dentin can be regenerated in the root canal space. It
      is foreseeable that a decade or two from now, regenerative endodontics is likely
      to be an alternative treatment modality for clinical endodontics. It is therefore
      important for us to understand stem cells and tissue regeneration and be prepared
      for this clinical practice.

PMID- 21905367
TI  - A matter of money.

PMID- 21905368
TI  - Chief nursing officer post to be downgraded in DH shake-up.

PMID- 21905369
TI  - CHRE calls for 'humane working environment' not HCA regulation.

PMID- 21905370
TI  - Soaring applications for degrees as interest in profession peaks.

PMID- 21905371
TI  - NHS managers told to tackle sickness rates with 'urgency'.

PMID- 21905372
TI  - The case for healthcare assistant regulation becomes overpowering.

PMID- 21905373
TI  - Are care complaints and worker satisfaction linked?

PMID- 21905375
TI  - Notes from an outsider.
AB  - About 1,000 nurses from overseas live in the UK as refugees, but many cannot work
      due to an English language test.

PMID- 21905374
TI  - Healing the sole.
AB  - The benefits of reflexology are explored in the fourth article in our series on
      complementary and alternative therapies.

PMID- 21905376
TI  - Space-age operations.
AB  - Robotic surgery at Kent and Canterbury Hospital has enabled a nurse specialist to
      extend her role and assist a surgeon with operations.

PMID- 21905377
TI  - Data on tap.
AB  - Renal PatientView is an innovative online resource for patients who have kidney
      disease. It enables them to access blood test results and information about their
      diagnosis and treatment from anywhere in the world.

PMID- 21905378
TI  - Supporting the lecturer to deliver high-fidelity simulation.
AB  - In response to a shortage of clinical practice placements for pre-registration
      nurses and midwives, nursing faculties have been examining alternative ways to
      support students to develop their clinical skills, with simulation being one of
      the more popular methods. In a nursing context, simulation is often used to
      replicate a clinical setting, such as a hospital ward or the patient's home. Some
      universities have introduced clinical suites that enable replication of clinical
      environments and offer the use of human patient simulators to mimic patient
      focused scenarios. This article describes a small informal review that aimed to
      identify how lecturers felt about simulation in one faculty using high-fidelity
      simulated scenarios to inform the development of a subsequent research study. The
      results indicate that although many staff use simulation and believe it is a
      beneficial approach to learning, many also lack confidence and do not feel
      sufficiently prepared in its use. Most participants felt that the development of
      a simulation module for lecturers would increase their confidence.

PMID- 21905379
TI  - Caring for a patient newly diagnosed with COPD: a reflective account.
AB  - In this article I reflect on my role as a respiratory nurse specialist caring for
      a patient newly diagnosed with chronic obstructive pulmonary disease (COPD). The
      aim of the article is to demonstrate the importance of specialist and holistic
      care for patients with COPD, as well as highlighting the need to carry out a
      thorough assessment to ensure that an accurate diagnosis is obtained and an
      appropriate plan of care is initiated. A model of reflection is used to promote
      self-awareness and provide a framework for reflection.

PMID- 21905380
TI  - Care of patients following liver transplantation.
AB  - This article provides an overview of the care of patients following liver
      transplantation. It focuses on the immediate post-operative care, the role of the
      transplant co-ordinator in providing support and education and the long-term
      follow up required to promote health and quality of life in this specific patient
      group.

PMID- 21905381
TI  - Nutrition.

PMID- 21905382
TI  - A sense of structure.

PMID- 21905383
TI  - Top care down under.

PMID- 21905384
TI  - Finding the feel-good factor.

PMID- 21905385
TI  - Mesothelioma in an individual following exposure to crocidolite-containing
      gaskets as a teenager.
AB  - Mesothelioma is considered a signal tumor for asbestos exposure and typically
      occurs decades after first exposure to asbestos. Tissue analysis often indicates
      past exposure to mixed types of asbestos. This report describes the case of a 58
      year-old man who developed mesothelioma after reported exposure to crocidolite
      from asbestos-containing gaskets beginning at age 16 during three summers during
      high school and for approximately four hours per day during the last semester of
      his senior year. He had no further known exposure to asbestos. Analytical
      transmission electron microscopy analysis of digested tissue samples revealed
      elevated levels of crocidolite asbestos fibers and the presence of crocidolite
      cored ferruginous bodies. This case is unique in that it establishes that
      relatively short and/or intense exposures to crocidolite asbestos traumatically
      released from a previously classified Category 1 nonfriable asbestos-containing
      material (NESHAP) was confirmed via tissue burden analysis years following the
      historically defined exposures.

PMID- 21905387
TI  - Carbon monoxide poisoning in the United Arab Emirates.
AB  - Carbon monoxide (CO) poisoning is rare in the Arabian Peninsula and occurs almost
      exclusively during the winter months. Knowledge and perception of the hazards of
      carbon monoxide is limited. Migrant workers from warm climates appear
      particularly at risk. We investigated 46 cases of carbon monoxide poisoning
      presenting at emergency departments from 2007-2009 of the two main hospitals in
      Al Ain city, United Arab Emirates. Interviews, hospital records, and administered
      questionnaires were used to collect the data. Among the 46 cases investigated, 24
      (52%) were males. Foreign nationals compromised 80% of the cases and the
      incidence was 3.1 cases per 100,000 residents per year. Burning charcoal in
      poorly ventilated residences was the predominant source of the carbon monoxide
      poisoning. Almost all cases (98%) were admitted during the winter months, most in
      the early morning hours. Carboxyhaemoglobin (COHb) was significantly increased in
      cases with loss of consciousness and depressed consciousness. There were no
      reported fatalities.

PMID- 21905386
TI  - Congenital anomalies in the offspring of nurses: association with area of
      employment during pregnancy.
AB  - The purpose of this study was to determine whether registered nurses in specific
      areas of employment during pregnancy had a higher risk for congenital anomalies
      in their offspring. An offspring cohort (n = 22,611) was created through linkage
      of the British Columbia Vital Statistics Agency live and stillbirth records from
      1986 to 2000, to a female cohort database of registered nurses. Of these, 16,005
      (70.8%) were registered in a specific area of employment when pregnant. Odds
      ratios were calculated using generalized estimating equations (GEE), binary
      logistic regression with adjustment for sex, mother's age, and year of birth.
      Elevated risks of congenital anomalies were found for the singleton offspring of
      nurses employed in the following areas: operating rooms and pediatric nursing
      units (heart anomalies); maternal newborn units (integument); emergency room
      (respiratory system); and psychiatry (upper alimentary tract). Further research
      is needed to determine whether these are chance or consistent findings and
      whether exposure patterns might provide biological plausibility.

PMID- 21905388
TI  - Acute silicosis in teflon-coated pan manufacturing due to metal sandblasting.
AB  - Sandblasting is one of the occupational causes of silicosis. This report details
      three cases diagnosed as silicosis caused by sandblasting in Teflon-coated pan
      manufacturing: Case 1--A 24-year-old man admitted with dyspnea and cough; Case 2-
      An 18-year-old man admitted with shortness of breath and fever; and Case 3--A 25
      year-old man admitted with dyspnea and weight loss. Chest examinations of the
      first and second cases revealed crackles in both lungs, but the third case was
      normal, no crackles. Chest x-rays showed bilateral reticulonodular densities and
      hilar enlargement in all cases. They were clinically and radiologically diagnosed
      as silicosis due to occupational exposure. All cases had worked in the
      sandblasting unit at a Teflon-coated pan manufacturing factory for one to three
      years. Silicosis is a preventable occupational lung disease, but no effective
      treatment is available for the disease yet. Improving workplace conditions is the
      most effective way to prevent silicosis.

PMID- 21905389
TI  - Occupational injury in rural Bangladesh: data gathering using household survey.
AB  - Occupational injuries are estimated to cause over 300,000 deaths per year
      worldwide. Many low- and middle-income countries often lack effective injury
      surveillance systems. We attempted to utilize household surveys to collect
      occupational injury data to develop more accurate injury incidence data. We
      undertook a pilot study of this approach in the rural area of Mirsarai,
      Bangladesh. Surveys were administered to 2,017 males and 120 females. Sixty-five
      percent were self-employed and over 80% worked in work places with less than six
      employees; over 60% worked seven days per week. Just over 50% of subjects
      reported at least one injury at work in the prior year. Incidence of lost-time
      injuries was 31%. The median number of work days lost was 7. The injury rates
      were higher than ILO estimates for Bangladesh, perhaps because of our study's
      focus on a rural population. We recommend expanding to larger and a more
      representative sample of the Bangladesh working community.

PMID- 21905390
TI  - SALTRA: a regional program for workers' health and sustainable development in
      Central America.
AB  - In 2003, the university-based Program on Work and Health in Central America,
      SALTRA, was launched to build national and regional capacities in occupational
      safety and health with the goal of preventing and reducing poverty in Central
      America. SALTRA has implemented 20 projects including action projects in priority
      sectors (e.g., construction, sugarcane, hospitals, migrant coffee workers);
      strengthening of surveillance (occupational health profiles, carcinogenic
      exposures, fatal injuries and pesticides); a participatory model for training and
      risk monitoring by workers; building occupational health capacity for
      professionals, employers, and workers, with collaborating networks between the
      countries; strengthening of universities in work, environment, and health;
      studies of serious occupational and environmental situations; communication
      channels; and continued efforts to raise political awareness. SALTRA has placed
      issues of workers' health on political, business, and academic agendas throughout
      the region and has laid the foundations for achieving substantial future
      improvements in health conditions of all workers in the region. External
      evaluators envisioned SALTRA as an innovative development model.

PMID- 21905391
TI  - Social determinants of workers' health in Central America.
AB  - This communication summarizes the available data on work-related determinants of
      health in Central America. The Central American working population is young and
      moving from agriculture toward industry and services. Ethnicity, gender,
      migration, subemployment and precarious work, informality, rural conditions, low
      level educational, poverty, ubiquitous worksite health hazards, insufficient
      occupational health services, low labor inspection density, and weak unions
      define the constellation of social determinants of workers' health in Central
      America. Data are, however, scanty both for hazards and work-related illnesses
      and injuries. Governments and industries have the responsibility of opening
      decent work opportunities, especially for those facing multiple inequalities in
      social determinants of health. A first step would be the ratification and
      implementation of the ILO Convention (187) on occupational safety and health by
      the seven national governments of the region.

PMID- 21905392
TI  - Fatal occupational injuries in Nicaragua, 2005.
AB  - We attempt to estimate the rate of fatal occupational injuries (FOI) in Nicaragua
      for 2005, using 10 incomplete data sources. Based on the 173 identified FOIs, the
      crude empirical FOI rate estimate was 8.3 per 100,000 employed (12.3 men; 1.8
      women) and highest in the 25-29 age group (15). The overall rate, corrected by
      capture-recapture modeling, was 11.6. Manufacturing represented a high rate
      (11.7); the formal economy rate (12.3) was higher than the informal economy (6);
      mining (110.3) and electricity (76.2) had the highest industry rates; and the
      most common agents of FOIs were motor vehicles. With 10 major sources, the extent
      of FOIs remains grossly underestimated and biased across worker strata. The FOIs
      among informal and agricultural workers tend to remain invisible, as there is no
      systematic surveillance by any agency. Changes in legislation and implementation
      are necessary to correct the situation.

PMID- 21905393
TI  - Registration of fatal occupational injuries in Costa Rica, 2005-2006.
AB  - Data on fatal occupational injuries (FOIs) for Latin America are controversial.
      Costa Rican national rates are inconsistent with estimates extrapolated from
      other countries. We reviewed the files for all possible FOIs in Costa Rica for
      2005-2006 at the National Insurance Institute and at the Center of Forensic
      Sciences by formality/informality of work, sex, age, economic activity,
      occupation, and cause of death. The national mortality rate was estimated at
      9.5/100,000 person-years (342 deaths). The informal/formal rate ratio was 1.06.
      Men's rates were over 10 times higher than women's and increased with age. The
      highest rates were found for transport, storage, and communication (32.1/100,000
      person-years), and, by occupation, for messengers and delivery men (91.4).
      Leading causes of death were traffic injuries and gunshots. Recalculated rates
      are probably underestimates. Data limitations include the absence of systematic
      identification and registration among informal sector workers and other groups
      such as children and farm workers.

PMID- 21905394
TI  - CAREX Nicaragua and Panama: Worker exposures to carcinogenic substances and
      pesticides.
AB  - This study provides data on numbers of workers exposed at work to selected
      carcinogens and pesticides in Nicaragua (35 substances) and Panama (31), based on
      a modification of the CAREX data system. Population censuses provided industry-
      and sex-specific workforce numbers. The activity- and sex-specific proportions of
      exposed workers were estimated by experts from governmental agencies, workers'
      organizations, and employers' representatives. Finally, the numbers of those
      occupied in each activity/sex category were multiplied by the proportions of
      those exposed in the same categories, yielding numbers of those exposed in these
      categories for each agent. The study revealed high proportions (> 9%) of
      occupationally exposed workers in both countries for solar radiation and diesel
      engine emissions; environmental tobacco smoke in Panama; and some pesticides in
      Nicaragua. A high proportion of exposed was found for men for lead (12%), silica
      dust (10%), and hexavalent chromium (10%) in Panama.

PMID- 21905396
TI  - Climate change, workplace heat exposure, and occupational health and productivity
      in Central America.
AB  - Climate change is increasing heat exposure in places such as Central America, a
      tropical region with generally hot/humid conditions. Working people are at
      particular risk of heat stress because of the intrabody heat production caused by
      physical labor. This article aims to describe the risks of occupational heat
      exposure on health and productivity in Central America, and to make tentative
      estimates of the impact of ongoing climate change on these risks. A review of
      relevant literature and estimation of the heat exposure variable wet bulb globe
      temperature (WBGT) in different locations within the region were used to estimate
      the effects. We found that heat stress at work is a real threat. Literature from
      Central America and heat exposure estimates show that some workers are already at
      risk under current conditions. These conditions will likely worsen with climate
      change, demonstrating the need to create solutions that will protect worker
      health and productivity.

PMID- 21905395
TI  - Monitoring pesticide use and associated health hazards in Central America.
AB  - We established methods for monitoring pesticide use and associated health hazards
      in Central America. With import data from Belize, Costa Rica, El Salvador,
      Guatemala, Honduras, Nicaragua, and Panama for 2000-2004, we constructed
      quantitative indicators (kg active ingredient) for general pesticide use,
      associated health hazards, and compliance with international regulations. Central
      America imported 33 million kg active ingredient per year. Imports increased 33%
      during 2000-2004. Of 403 pesticides, 13 comprised 77% of the total pesticides
      imported. High volumes of hazardous pesticides are used; 22% highly/extremely
      acutely toxic, 33% moderately/severely irritant or sensitizing, and 30% had
      multiple chronic toxicities. Of the 41 pesticides included in the Stockholm
      Convention on Persistent Organic Pollutants (POPs), the Rotterdam Convention on
      Prior Informed Consent (PIC), the Montreal Protocol on Substances that Deplete
      the Ozone Layer, the Pesticide Action Network (PAN) Dirty Dozen, and the Central
      American Dirty Dozen, 16 (17% total volume) were imported, four being among the
      13 most imported pesticides. Costa Rica is by far the biggest consumer. Pesticide
      import data are good indicators of use trends and an informative source to
      monitor hazards and, potentially, the effectiveness of interventions.

PMID- 21905397
TI  - Stop Canadian death export of asbestos.

PMID- 21905398
TI  - Development of a fluoridated, daily-use toothpaste containing NovaMin technology
      for the treatment of dentin hypersensitivity.

PMID- 21905399
TI  - Physical and chemical characterization of dentin surface following treatment with
      NovaMin technology.
AB  - OBJECTIVE: The aim of this study was to characterize, in vitro, the mode of
      action of calcium sodium phosphosilicate (NovaMin) in occluding dentin tubules
      for the purpose of treating dentin hypersensitivity. METHODS: Calcium sodium
      phosphosilicate (CSPS) was combined with artificial saliva on surfaces of
      prepared dentin discs. The layer formed was initially examined by a scanning
      electron microscope (SEM). Focused ion beam (FIB) milling was used to make bulk
      cross-sections and thin film lamellae. Low kV scanning transmission electron
      microscopy (STEM), energy dispersive x-ray spectroscopy (EDS), and selected area
      electron diffraction were then used to characterize, chemically and structurally,
      the layer formed and the material occluding the tubules. Experiments were also
      performed to assess the suitability of using an environmental scanning electron
      microscope (ESEM) in wet mode to follow the transition from CSPS to
      hydroxyapatite. RESULTS: SEM imaging showed that a layer was formed on the
      treated dentin samples, and that this layer occluded tubules. Chemical and
      structural analysis of this material showed that it was hydroxyapatite-like. The
      wet mode ESEM experiments demonstrated that this technique has the potential to
      follow the transition from CSPS to the crystalline hydroxyapatite material.
      CONCLUSION: The use of modern imaging and analysis techniques has demonstrated,
      in vitro, the reaction of CSPS from an amorphous material to a crystalline
      hydroxyapatite-like material. These experiments confirmed an occlusion mode of
      action for CSPS for the treatment of dentin hypersensitivity.

PMID- 21905400
TI  - Physical and chemical characterization of the surface layers formed on dentin
      following treatment with a fluoridated toothpaste containing NovaMin.
AB  - OBJECTIVE: To characterize in vitro the formation and robustness of a layer
      formed on dentin following treatment with a fluoridated toothpaste containing
      calcium sodium phosphosilicate (NovaMin) using modem imaging and analysis
      techniques. METHODS: Calcium sodium phosphosilicate (CSPS)-containing toothpaste
      was brushed on to etched dentin specimens twice daily for up to five days. In
      between applications the samples were stored in artificial saliva. Additionally,
      certain samples underwent a chemical challenge in the form of a dietary acid,
      whereby samples were exposed to a cola or grapefruit juice beverage for five
      minutes on day 4 of the five-day study. The ability of the CSPS-containing
      formulation to occlude tubules was assessed visually by scanning electron
      microscope (SEM) imaging and compared to a water control. In a second experiment,
      the mechanical resistance of the layer was assessed using profilometry after
      controlled brushing for 200 brush strokes with a wet medium-bristled toothbrush.
      To visualize the layer and characterize the tubule occlusion, longitudinal cross
      sections were prepared using a focused ion beam scanning electron microscope (FIB
      SEM), and analysis performed by energy dispersive x-ray spectroscopy (EDS) and
      electron diffraction. Owing to the complexity of the mixed material deposited
      after application of the toothpaste, material from inside a dentin tubule was
      selectively removed after five days of treatment, and the morphologically
      different materials imaged and analyzed by electron diffraction in the
      transmission electron microscope (TEM). RESULTS: SEM inspection showed
      significant coverage of the dentin samples after application of CSPS toothpaste
      for all five days, in contrast to the water control where the majority of tubules
      remained open after all five days. Exposure of the NovaMin-treated samples to
      common dietary acids did not lead to re-exposure of the tubules. Profilometry
      measurements demonstrated an intact layer covering the dentin surface after one
      and five days. EDS analysis and electron diffraction indicated the layer and the
      material plugging the tubule to be a calcium phosphate material with a
      crystallographic structure similar to hydroxyapatite. CONCLUSION: CSPS contained
      in toothpaste formulations adhered to exposed dentin surfaces. The layer formed
      was resistant to acid and mechanical challenges. Characterization of this layer
      indicated it was hydroxyapatite-like in nature.

PMID- 21905401
TI  - A comparative in vitro study investigating the occlusion and mineralization
      properties of commercial toothpastes in a four-day dentin disc model.
AB  - OBJECTIVE: The objective of this study was to evaluate the relative level of
      dentin tubule occlusion and dentin mineralization conferred by a 5% w/w calcium
      sodium phosphosilicate (45S5)/1450 ppm fluoride toothpaste in comparison to a
      range of commercial toothpastes reported to occlude dentin tubules. METHODS: Two
      separate experiments were employed to (i) determine the level of dentin tubule
      occlusion, and (ii) explore the change in dentin mineralization conferred by a
      number of marketed toothpastes and controls, following twice-daily brushing in a
      longitudinal, acid challenge-based, dentin disc model. In Study I, 192 bovine
      dentin discs, polished and etched in citric acid to provide a smooth dentin
      surface with patent tubules, were divided into eight treatment groups and
      subjected to brushing with one of seven test toothpastes or deionized water over
      four days. Prior to and between treatments, the dentin samples were stored in
      saliva. The test products were fluoridated toothpastes containing: calcium sodium
      phosphosilicate (45S5); strontium acetate; arginine/calcium carbonate; amine
      fluoride; calcium sulphate/diphosphate; stannous fluoride; casein stabilized
      amorphous calcium phosphate toothpaste; and a non-occluding negative control,
      deionized water. At the end of each treatment day (1 though 4), one group of
      samples was removed for scanning electron microscopy (SEM) analysis and graded on
      a categorical visual scale to assess the level of dentin tubule occlusion. A
      subset of samples from Study I was also cross-sectioned and examined using SEM.
      For the exploratory mineralization study (Study II), 120 dentin specimens were
      prepared as previously described and divided into four treatment groups
      consisting of A, C, F, and a tooth sealant varnish (I), and subjected to the
      treatment regimen described in Study I. The dentin samples were assessed for
      changes in surface microhardness using an indenter fitted with a Knoop probe and
      the level of dentin occlusion. RESULTS: In Study I, the 5% w/w calcium sodium
      phosphosilicate/1450 ppm fluoride-containing toothpaste (A), the stannous
      fluoride-containing toothpaste (F), and the strontium acetate-containing
      toothpaste (B) delivered the highest level of occlusion following four days of
      twice-daily brushing and a twice-daily acid challenge on days 3 and 4. Surface
      analysis of a subset of Study I samples, following four days of treatment,
      indicated that the 5% w/w calcium sodium phosphosilicate/1450 ppm fluoride
      containing toothpaste formed a distinct layer at the surface of dentin. For Study
      II, surface microhardness analysis revealed that the 5% w/w calcium sodium
      phosphosilicate/1450 ppm fluoride-containing toothpaste (A) delivered
      significantly more surface hardening then the control or competitor toothpastes
      on days 2 and 4. CONCLUSION: Desensitizing toothpastes reported to operate by an
      occlusion mechanism have been observed to confer varying degrees of dentin tubule
      occlusion and dentin mineralization over four days in an acid challenge-based in
      vitro model. A 5% w/w calcium sodium phosphosilicate/1450 ppm fluoride-containing
      toothpaste was observed to impart a significant level of dentin tubule occlusion
      and surface hardening, and form durable occlusive deposits following four days of
      twice-daily brushing in vitro.

PMID- 21905402
TI  - Randomized in situ clinical study comparing the ability of two new desensitizing
      toothpaste technologies to occlude patent dentin tubules.
AB  - OBJECTIVE: To compare the ability of two new desensitizing toothpaste
      technologies (one a 5% NovaMin-based toothpaste and the other an 8% arginine
      based toothpaste) to occlude patent dentin tubules in a clinical environment
      relative to a negative control of water and a control toothpaste after four days
      of twice-daily brushing and dietary acidic challenges. METHODS: The study design
      was a single-center, single-blind, randomized, split-mouth, four-treatment, two
      period, crossover, in situ clinical study. Healthy subjects wore two lower intra
      oral appliances, retaining four dentin samples for four treatment days for each
      period of the clinical study. Samples were brushed twice daily with a test
      product (days 1-4), with an additional acidic challenge introduced on two
      selective days. Scanning electron microscopy (SEM) images were taken of the
      dentin surface, and dentinal tubule occlusion assessed using a categorical scale.
      RESULTS: The results demonstrated that the 5% NovaMin toothpaste was
      statistically superior at occluding patent dentin tubules compared to water (p =
      0.009) and the control toothpaste (p = 0.02) at day 4. In contrast, the treatment
      effect resulting from the 8% arginine toothpaste did not demonstrate the same
      degree of occlusive propensity, showing no significant difference to the water
      and control toothpaste at the day 4 time point. CONCLUSION: Application of the 5%
      NovaMin toothpaste to dentin showed better dentin tubule occlusion and retention
      abilities in an oral environment under dietary acid challenge conditions, more so
      than the 8% arginine toothpaste technology. Given modern dietary habits and
      practices, these results highlight differences in the acid resistance properties
      of occlusion technologies, and a potential impact on clinical performance.

PMID- 21905403
TI  - Overview of the clinical evidence for the use of NovaMin in providing relief from
      the pain of dentin hypersensitivity.
AB  - Dentin hypersensitivity is a common condition that affects the adult population
      worldwide. NovaMin is technically described as amorphous sodium calcium
      phosphosilicate, and has been shown in laboratory studies to rapidly occlude
      dentin tubules and form a protective hydroxyapatite-like layer on the dentin
      surface. A number of clinical studies investigating the efficacy of NovaMin for
      the relief of pain from dentin hypersensitivity have been conducted in the United
      States, Ireland, China, and India. This article reviews the available literature
      and finds support based on randomized controlled clinical trials for the use of
      NovaMin in anhydrous toothpaste formulations in providing relief of pain from
      dentin hypersensitivity.

PMID- 21905404
TI  - Measurement of organic nitrogen and phosphorus fractions at very low
      concentrations in wastewater effluents.
AB  - The purpose of this study was to develop simple, accurate, and inexpensive
      measurement protocols for dissolved organic nitrogen (DON) and dissolved non
      reactive phosphorus (DNRP) at low levels in wastewater effluents. Two protocols
      are presented--one to measure DON exclusively, and the other to measure DON and
      DNRP simultaneously. Currently, DON and DNRP are calculated indirectly by
      subtracting the dissolved inorganic fractions from the total dissolved
      concentration, resulting in significant errors. To increase the accuracy of DON
      measurements, effluent sample pretreatment using ion exchange to remove nitrate
      was applied. Spectrometric methods were selected to measure the inorganic
      fractions-the second derivative UV spectroscopy method for nitrate, and the
      malachite green method for orthophosphate. These methods, combined with the
      optimized persulfate digestion of the samples, can be used to measure total
      dissolved nitrogen and phosphorus accurately. The measurement ranges attained
      were 0.05 to 3 mg N/L for DON and 0.01 to 0.5 mg P/L for DNRP.

PMID- 21905405
TI  - Removal of selected endocrine disrupting chemicals and personal care products in
      surface waters and secondary wastewater by ozonation.
AB  - This study investigated the removal of parabens, N,N-diethyl-m-toluamide (DEET),
      and phthalates by ozonation. The second-order rate constants for the reaction
      between selected compounds with ozone at pH 7 were of (2.2 +/-0.2) X 10(6) to
      (2.9 +/-0.3) X 10(6) M 1/s for parabens, (2.1+/- 0.3) to (3.9 +/-0.5) M-1/s for
      phthalates, and (5.2 +/-0.3) M-1/s for DEET. The rate constants for the reaction
      between selected compounds with hydroxyl radical ranged from (2.49 +/-0.06) x
      10(9) to (8.5 +/-0.2) x 10(9) M-1/s. Ozonation of selected compounds in secondary
      wastewater and surface waters revealed that ozone dose of 1 and 3 mg/L yielded
      greater than 99% depletion of parabens and greater than 92% DEET and phthalates,
      respectively. In addition, parabens were found to transform almost exclusively
      through the reaction with ozone, while DEET and phthalates were transformed
      almost entirely by hydroxyl radicals (.OH).

PMID- 21905406
TI  - Hydraulic response and nitrogen retention in bioretention mesocosms with
      regulated outlets: part I--hydraulic response.
AB  - In bioretention systems used for stormwater treatment, runoff interception
      improves with increased infiltration rates. However, nitrogen retention improves
      with increased retention time or decreasing infiltration rates. These contrasting
      responses were analyzed in 240-L experimental mesocosms using a variety of media
      treatments. The mesocosms were vegetated, except for one barren control. Dual
      stage outlets were installed to extend retention time and equalize hydraulic
      responses. One unregulated treatment was free-draining. This part 1 paper
      presents the media properties and hydraulic responses. The highly aggregated
      media had saturated hydraulic conductivities ranging from 20.7 to 59.6 cm/h in
      August 2008 (austral winter), which increased to 42.8 to 110.6 cm/h in March 2009
      (austral summer). The outlet regulated mesocosms provided retention over 8 times
      longer than the free-draining mesocosms, while still being able to capture large
      events. The outlets provide adaptive management for bioretention design to
      improve both runoff capture and nitrogen retention.

PMID- 21905407
TI  - Hydraulic response and nitrogen retention in bioretention mesocosms with
      regulated outlets: part II--nitrogen retention.
AB  - We observed dissolved nitrogen retention in vegetated bioretention mesocosms
      using different media with varying hydraulic conductivities. Elevated outlets
      were installed to regulate hydraulic response, with one treatment left free
      draining. The treatments (three replicates each) were loaded weekly with 50 cm of
      effluent averaging 2.47 mg/L nitrogen oxides (NOx) and 4.67 mg/L total nitrogen
      for 1 year. The NOx and total nitrogen retention by the outlet regulated
      treatments was significantly greater than the unregulated treatment. The systems
      then were dosed 6 times with 53 cm of synthetic stormwater averaging 0.77 mg/ L
      NOx and 1.46 mg/L total nitrogen, applied over 90 minutes. The outlet regulated
      treatment retained 68% NOx and 60% total nitrogen, while the corresponding free
      draining treatment retained 25% NOx and 27% total nitrogen. Over the following
      winter, the outlet regulated treatment retained 50% NOx and 73% total nitrogen,
      while the corresponding free draining treatment exported 17% more NOx, while
      retaining 50% total nitrogen.

PMID- 21905408
TI  - A potential sanitary sewer overflow treatment technology: fixed-media
      bioreactors.
AB  - Under certain conditions, sanitary sewer overflows (SSOs) containing raw
      wastewater may be discharged to public land and can contribute to environmental
      and public health issues. Although this problem has attracted the attention of
      local, state, and federal government and regulators, relatively little SSO
      abatement research has been published. This study used fixed-media bioreactors, a
      proven onsite technology in rural areas, to treat wet weather SSO wastewater and
      reduce its effects on the receiving water environment. The results of this 32
      month laboratory study showed that fixed-media bioreactors, especially sand
      bioreactors, efficiently removed organic matter, solids, and nutrients during six
      hour simulated SSO peak flows. Five-day biochemical oxygen demand (BODs) of the
      simulated SSO varied between 40 and 125 mg/L. The average effluent concentration
      of BOD5 was 13 mg/L in sand bioreactors at a hydraulic loading rate of 20.4 cm/h.
      In addition to having high hydraulic loadings, SSO events occur infrequently.
      This irregularity requires that treatment systems quickly start up and
      effectively treat wastewater after a period of no flow. This research found that
      an interval up to six months between two SSO peak flows did not affect the
      bioreactor performance. Based on this work, fixed-media bioreactors have the
      potential to reduce the effects of SSOs on the water environment by following
      proper design parameters and operation strategies. The pollution loading of
      approximately 18 g BODs/m2 x h is recommended for the efficient performance of
      sand bioreactors in the SSO treatment.

PMID- 21905409
TI  - Improving nitrogen removal in two modified decentralized wastewater systems.
AB  - Efficient nutrient removal in decentralized wastewater treatment systems is a
      challenging task. To improve the removal of organic matter and nitrogen from
      wastewater, two types of bioreactors using membrane-aerated biofilm reactor
      (MABR) and microbial fuel cell (MFC) techniques were evaluated. During more than
      250 days of continuous-flow reactor operation, both reactors showed consistently
      high chemical oxygen demand removal (>86%). At an influent ammonium-nitrogen
      (NH4(+)-N) concentration of 30 mg N/L, the average effluent NH4(+)-N
      concentrations were 6.2 and 0.5 mg N/L for the MABR and MFC reactor,
      respectively, while the effluent nitrate-nitrogen (NO3(-)-N) concentrations were
      5.4 mg/ L in the MABR and 19.2 mg/L in the MFC-based reactor. The overall total
      inorganic nitrogen removal efficiencies were 64% and 36% for the MABR and MFC
      reactor, respectively. At the measured dissolved oxygen concentrations of 5.2 and
      0.23 mg/L in the aerobic/anoxic zone of the MFC and MABR, respectively, a
      specific oxygen uptake rate of 0.1 g O2/g VSS-d, resulting from ammonia
      oxidation, was detected in the settled sludge of the MFC, while no nitrifying
      activity of the sludge from the MABR was detected. Molecular microbial analysis
      demonstrated a link between the bacterial community structure and nitrifying
      activity. The relatively high abundance of Nitrosomonas europaea was associated
      with its detectable nitrification activity in the settled sludge of the MFC. The
      results suggest that MABR and MFC techniques have the potential to improve
      organic and nitrogen removal in decentralized wastewater systems.

PMID- 21905410
TI  - Integrated physicochemical and biological treatment process for fluoride and
      phosphorus removal from fertilizer plant wastewater.
AB  - The phosphate fertilizer industry produces highly hazardous and acidic
      wastewaters. This study was undertaken to develop an integrated approach for the
      treatment of wastewaters from the phosphate industry. Effluent samples were
      collected from a local phosphate fertilizer producer and were characterized by
      their high fluoride and phosphate content. First, the samples were pretreated by
      precipitation of phosphate and fluoride ions using hydrated lime. The resulting
      low- fluoride and phosphorus effluent was then treated with the enhanced
      biological phosphorus removal (EBPR) process to monitor the simultaneous removal
      of carbon, nitrogen, and phosphorus. Phosphorus removal included a two-stage
      anaerobic/aerobic system operating under continuous flow. Pretreated wastewater
      was added to the activated sludge and operated for 160 days in the reactor. The
      operating strategy included increasing the organic loading rate (OLR) from 0.3 to
      1.2 g chemical oxygen demand (COD)/L.d. The stable and high removal rates of COD,
      NH4(+)-N, and PO4(3-)-P were then recorded. The mean concentrations of the
      influent were approximately 3600 mg COD/L, 60 mg N/L, and 14 mg P/L, which
      corresponded to removal efficiencies of approximately 98%, 86%, and 92%,
      respectively.

PMID- 21905411
TI  - Efficacy and reliability of upgraded industrial treatment plant at Porto
      Marghera, near Venice, Italy, in removing nutrients and dangerous micropollutants
      from petrochemical wastewaters.
AB  - Chemical and petrochemical wastewaters contain a host of contaminants that
      require different treatment strategies. Regulation of macropollutants and
      micropollutants in the final discharge from industrial wastewater treatment
      plants (WWTPs) have become increasingly stringent in recent decades, requiring
      many WWTPs to be upgraded. This article presents an analysis of a WWTP treating
      petrochemicals in Porto Marghera, Italy, that recently was upgraded following
      legislative changes. Because of strict legal limits for macropollutants and
      micropollutants and a lack of space necessary for a full-scale WWTP overhaul, the
      existing activated sludge tank was converted into a membrane biological reactor.
      The paper presents experimental data collected during a five-month investigation
      showing the removal rates achieved by the upgraded plant for macropollutants
      (particularly nitrogen compounds) and micropollutants (heavy metals and organic
      and inorganic toxic compounds).

PMID- 21905412
TI  - A comparative environmental life-cycle analysis for removing phosphorus from
      wastewater: biological versus physical/ chemical processes.
AB  - Phosphorus can be removed from wastewater biologically, chemically, or through a
      combination of the two. In this study, we applied environmental life-cycle
      assessment to develop a metric with which decision-makers can compare processes.
      Two phosphorus-removal scenarios were contrasted-one based on a desktop-level
      design and one based on full-scale operational data. To achieve 0.5 mg/L effluent
      phosphorus (desktop design), a biological-only process would incur 5.2% less
      effect on global warming potential, as contrasted with a chemical-only process.
      At an effluent quality of 0.1 mg/L (full-scale facilities), where a biological
      process augmented with chemicals was contrasted with a chemical-only process, the
      relative gap increases to 13.2%. As chemical usage increased, the adverse
      environmental effect of chemical treatment only increased. The results of this
      study suggest that best practices would center phosphorus removal first on the
      biological process, with chemical processes added only as necessary.

PMID- 21905413
TI  - Effect of influent nitrogen speciation on organic nitrogen occurrence in
      activated sludge process effluents.
AB  - The effect of influent nitrogen composition on organic nitrogen production in a
      sequencing batch reactor (SBR) activated sludge process was investigated. A
      laboratory-scale SBR was fed with three different type synthetic wastewaters with
      varying nitrogen compositions (phase I = nitriloacetic acid + ammonium [NH4-N],
      phase II = NH(4-)N, and phase III = amino acid mixture + NH(4-)N) was operated.
      The effluent contained approximately 1 to 2 mg N/L organic nitrogen, even though
      there was no organic nitrogen in influent. The effluent organic nitrogen
      increased to approximately 4 mg N/L when the influent composition was changed and
      then stabilized at <2 mg N/L. The maximum nitrifier growth rate constants
      (microN) were calculated as 0.91+/-0.10 to 1.14+/-0.08 day-1, 0.82 +/-0.13 day-1,
      and 0.89+/-0.08 day-1 at 20 degrees C for the three different influent
      compositions. The effluent colloidal organic nitrogen (CON) was negligible,
      suggesting that the effluent CON found in full-scale plants may be the result of
      influent-derived suspended matter.

PMID- 21905414
TI  - Obesity prevalence and nutritional habits among Indian women: a comparison
      between Punjabi women living in India and Punjabi migrants in Vienna, Austria.
AB  - The current study aimed to determine the prevalence of obesity and overweight
      among Indian women living in Punjab, India and in Vienna, Austria. A series of
      115 women ageing between 17 and 80 years (x = 38.7 yrs; +/- 14.5) was enrolled in
      the present study. 65 women lived in the district of Jalandhar in Punjab, 50
      Punjabi women lived in as migrants in Vienna Austria. Data collection comprised
      an anthropometric analysis including stature height, body weight and the body
      mass index (BMI). For classification of the weight status the Indian BMI cutoffs
      defined by the WHO for Asian Indians were used. Data concerning dietary patterns
      and lifestyle parameters were collected by structured interviews using a
      standardized questionnaire. Among both subgroups overweight and obesity were
      highly prevalent. Underweight (18.5%) was significantly more prevalent in Punjab
      than in Vienna (6.0 %), while overweight and obesity were more frequently found
      among Punjabi women in Vienna (26.0%; 54.0%) than among Punjabi women in India
      (9.2%; 24.6 %). Analysing lifestyle and dietary patterns it turned out that
      energy dense meals were preferred and fat and sugar were used frequently among
      both subsamples. A statistically significant relationship between dietary habits
      and weight status could not be proved.

PMID- 21905415
TI  - Prevalence of cardiovascular disease risk factors by habitat: a study on adult
      Asian Indians in West Bengal, India.
AB  - The present community based cross-sectional study was aimed to investigate
      whether or not increasing prevalence of cardiovascular disease (CVD) risk factors
      in adult Asian Indian population are associated with increasing urbanization. The
      'urban group' was comprised of 224 individuals including 122 males and 102
      females being inhabitants of Kolkata (erstwhile Calcutta) under the Kolkata
      Metropolitan Development Authority (KMDA) area. The 'rural group' comprised 224
      individuals including 135 males and 89 females and was living in a village
      council located about 80 kilometers from Kolkata. Therefore, a total of 448 adult
      (> or = 30 years) individuals (257 males and 191 females) participated in the
      study. Anthropometric measures, lipids profiles, fasting blood glucose and blood
      pressure measures were taken from participants. Obesity and body composition
      measures were subsequently calculated from the anthropometric measures. Accepted
      cut-offs were used to define metabolic syndrome (MS), lipids abnormalities,
      increased adiposity and high blood pressure in the study. It was found that 58.7%
      participants were engaged in sedentary work which includes 60.7% males and 56%
      females. It was further observed that the prevalence of high blood pressure was
      as high as 70.6% in urban females compared to 55.1% in rural females. However,
      the prevalence of low HDLc was remarkably high in females ofboth rural and urban
      areas. The prevalence ofMS was significantly higher in urban females (57.8%) than
      in their rural counterparts (34.8%). It seems reasonable to argue that people
      with changing lifestyles due to growing urbanization are associated with adverse
      CVD risk factors irrespective of their habitat (rural vs. urban). This in turn
      warranted a comprehensive risk stratification protocol at the national level for
      the effective management of CVD risk factors in this part of the world.

PMID- 21905416
TI  - Nutrition and immune system: the size of the thymus as an indicator of the
      newborn's nutrition status.
AB  - SUMMARY: The thymus is a central lymphatic organ reaching its largest size after
      the delivery. Its size is significantly affected by endogenous and exogenous
      negative factors. In our research, we investigated the relationship between the
      size of the thymus determined by sonography and anthropometric parameters as well
      as indexes demonstrating the nutritional status. The examined group consisted of
      212 full-term newborns, all of which passed an anthropometric examination during
      the first five days after delivery (birth weight and length, mid-arm and head
      circumference). The following nutritional status indexes were calculated from
      estimated anthropometric dimensions: Quetelet's index, Rohrer's index, birth
      weight-to-length ratio and mid-arm-to-head circumference ratio. The size of the
      thymus was assessed by sonography and expressed as the multiple of transversal
      width of the cranial thymus part and sagittal area of the major thymus lobe (so
      called 'Thymic Index'). The Thymic Index showed a positive correlation with the
      majority of indicators of the newborn's nutritional status, but all of these
      correlations are low (Spearman correlation coefficients 0.228-0.409). The
      correlation of the size of thymus with the birth weight or birth weight-to-length
      ratio was stronger than the correlation with the Quetelet's index or mid-arm
      circumference. The size of the thymus reflects the newborn's nutritional status
      assumed by anthropometry and can represent one of the "barometers of nutrition".
      Normal nutrition in the prenatal period plays a relatively critical role in the
      development of the immune system.

PMID- 21905417
TI  - Age diagnosis based on incremental lines in dental cementum: a critical
      reflection.
AB  - Age estimation based on the counting of incremental lines in dental cementum is a
      method frequently used for the estimation of the age at death for humans in
      bioarchaeology, and increasingly, forensic anthropology. Assessment of
      applicability, precision, and method reproducibility continue to be the focus of
      research in this area, and are occasionally accompanied by significant
      controversy. Differences in methodological techniques for data collection (e.g.
      number of sections, factor of magnification for counting or interpreting
      "outliers") are presented. Potential influences on method reliability are
      discussed, especially for their applicability in forensic contexts.

PMID- 21905418
TI  - Three palmar dermatoglyphic traits and their asymmetry in Bulgarian right-, mixed
      and left-handers.
AB  - SUMMARY: In a sample, comprising 264 right-, 246 mixed- and 360 left-handers (RH,
      MH and LH, correspondingly), the atd-angle, the a-b ridge count and the
      hypothenar radial arch were investigated, the asymmetry of both quantitative
      traits differentiated into directional (DA) and fluctuating (FA) one. Except for
      the FA of the a-b ridge count in females, which decreased significantly from RH
      to LH, the trends observed in the relations between the investigated
      dermatoglyphic values and handedness were not significant. In both quantitative
      traits the most important finding was the categorical left-palm excess over the
      right palm, since it was significantly related to sex and handedness, being much
      more expressed in females than in males and in the non-right-handers than in the
      right-handers. The hypothenar radial arch, along with its considerably higher
      frequency in females than in males and on the right palm than on the left, as
      well as its rarity combined with a very high symmetry, displayed another
      interesting peculiarity. The pattern was 3.9-fold more frequent in the MH and 3.4
      fold more frequent in the LH as compared to RH. As witnessed by the odds ratio,
      if a given palm belongs to a non-right-hander, the probability that it bears a
      hypothenar radial arch is nearly 4-fold higher than if it were a palm of a right
      hander. Arguments are adduced that left-handedness, although not a pathological
      character is, to say the least, a modified condition and that, similarly, the
      hypothenar radial arch is a subnormal dermatoglyphic finding. If such is the
      case, their relationship found by the present study is not surprising, although
      its causal background still remains unclear.

PMID- 21905419
TI  - Age at menarche in urban Argentinian girls: association with biological and
      socioeconomic factors.
AB  - Age at menarche is regarded as a sensitive indicator of physical, biological, and
      psychosocial environment. The aim of this study was to determine the age at
      menarche and its association with biological and socioeconomic factors in girls
      from Santa Rosa (La Pampa, Argentina). An observational cross-sectional study was
      carried out on 1,221 schoolgirls aged 9-15 years. Menarche data were obtained by
      the status-quo method. Height, sitting height, weight, arm circumference,
      tricipital and subscapular skinfolds were measured. We also calculated body mass
      index, measures of body composition and proportions, and fat distribution. To
      assess socioeconomic factors, parents completed a self-administered questionnaire
      about their occupation and education, family size, household, and other family
      characteristics. The median age at menarche - estimated by the logit method--was
      12.84 years (95% CI: 12.71, 12.97). Compared with their premenarcheal age peers,
      postmenarcheal girls had greater anthropometric dimensions through age 12. After
      this age, only height was higher in the latter group. Data were processed by
      fitting two logistic regressions, both including age. The first model included
      anthropometric variables and birth weight, while the second model included the
      socioeconomic variables. The significant variables derived from each model were
      incorporated into a new regression: height, sitting height ratio (first model),
      and maternal education (second model). These three variables remained
      significantly associated with menarche. The results suggest a relationship
      between linear growth and menarche and agree with those found in other
      populations where the advancement of menarche is associated with improved living
      conditions. In relatively uniform urban contexts, maternal education may be a
      good proxy for the standard of living.

PMID- 21905420
TI  - Changes in selected features of a male face and assessment of their influence on
      facial recognition.
AB  - The project aimed at finding the answers to the following two research questions:
      --To what extent does a change in size, height or width of the selected face
      feature influence the assessment of likeness between an original composite
      portrait and a modified one? --How does the sex of a person who judges the images
      have an impact on the perception of likeness of the face features? The results
      indicate that there are significant differences in the assessment of likeness of
      the portraits with some features modified to the original ones. The images with
      changes in size and height of the nose received the lowest scores on the likeness
      scale, which indicates that these changes were perceived by the subjects as the
      most important. The photos with changes in height and width of the lips, and
      height and width of the eye slit, in turn, received high scores of likeness, in
      spite of big changes. This signifies that these modifications were perceived to
      be of the least importance (compared to the other features investigated).

PMID- 21905421
TI  - Edge effects, not connectivity, determine the incidence and development of a
      foliar fungal plant disease.
AB  - Using a model plant-pathogen system in a large-scale habitat corridor experiment,
      we found that corridors do not facilitate the movement of wind-dispersed plant
      pathogens, that connectivity of patches does not enhance levels of foliar fungal
      plant disease, and that edge effects are the key drivers of plant disease
      dynamics. Increased spread of infectious disease is often cited as a potential
      negative effect of habitat corridors used in conservation, but the impacts of
      corridors on pathogen movement have never been tested empirically. Using sweet
      corn (Zea mays) and southern corn leaf blight (Cochliobolus heterostrophus) as a
      model plant-pathogen system, we tested the impacts of connectivity and habitat
      fragmentation on pathogen movement and disease development at the Savannah River
      Site, South Carolina, USA. Over time, less edgy patches had higher proportions of
      diseased plants, and distance of host plants to habitat edges was the greatest
      determinant of disease development. Variation in average daytime temperatures
      provided a possible mechanism for these disease patterns. Our results show that
      worries over the potentially harmful effects of conservation corridors on disease
      dynamics are misplaced, and that, in a conservation context, many diseases can be
      better managed by mitigating edge effects.

PMID- 21905422
TI  - Can dispersal mode predict corridor effects on plant parasites?
AB  - Habitat corridors, a common management strategy for increasing connectivity in
      fragmented landscapes, have experimentally validated positive influences on
      species movement and diversity. However, long-standing concerns that corridors
      could negatively impact native species by spreading antagonists, such as disease,
      remain largely untested. Using a large-scale, replicated experiment, we evaluated
      whether corridors increase the incidence of plant parasites. We found that
      corridor impacts varied with parasite dispersal mode. Connectivity provided by
      corridors increased incidence of biotically dispersed parasites (galls on
      Solidago odora) but not of abiotically dispersed parasites (foliar fungi on S.
      odora and three Lespedeza spp.). Both biotically and abiotically dispersed
      parasites responded to edge effects, but the direction of responses varied across
      species. Although our results require additional tests for generality to other
      species and landscapes, they suggest that, when establishing conservation
      corridors, managers should focus on mitigating two potential negative effects:
      the indirect effects of narrow corridors in creating edges and direct effects of
      corridors in enhancing connectivity of biotically dispersed parasites.

PMID- 21905423
TI  - Oxygen supply in aquatic ectotherms: partial pressure and solubility together
      explain biodiversity and size patterns.
AB  - Aquatic ectotherms face the continuous challenge of capturing sufficient oxygen
      from their environment as the diffusion rate of oxygen in water is 3 x 10(5)
      times lower than in air. Despite the recognized importance of oxygen in shaping
      aquatic communities, consensus on what drives environmental oxygen availability
      is lacking. Physiologists emphasize oxygen partial pressure, while ecologists
      emphasize oxygen solubility, traditionally expressing oxygen in terms of
      concentrations. To resolve the question of whether partial pressure or solubility
      limits oxygen supply in nature, we return to first principles and derive an index
      of oxygen supply from Fick's classic first law of diffusion. This oxygen supply
      index (OSI) incorporates both partial pressure and solubility. Our OSI
      successfully explains published patterns in body size and species across
      environmental clines linked to differences in oxygen partial pressure (altitude,
      organic pollution) or oxygen solubility (temperature and salinity). Moreover, the
      OSI was more accurately and consistently related to these ecological patterns
      than other measures of oxygen (oxygen saturation, dissolved oxygen concentration,
      biochemical oxygen demand concentrations) and similarly outperformed temperature
      and altitude, which covaried with these environmental clines. Intriguingly, by
      incorporating gas diffusion rates, it becomes clear that actually more oxygen is
      available to an organism in warmer habitats where lower oxygen concentrations
      would suggest the reverse. Under our model, the observed reductions in aerobic
      performance in warmer habitats do not arise from lower oxygen concentrations, but
      instead through organismal oxygen demand exceeding supply. This reappraisal of
      how organismal thermal physiology and oxygen demands together shape aerobic
      performance in aquatic ectotherms and the new insight of how these components
      change with temperature have broad implications for predicting the responses of
      aquatic communities to ongoing global climate shifts.

PMID- 21905424
TI  - Functional and phylogenetic diversity as predictors of biodiversity--ecosystem
      function relationships.
AB  - How closely does variability in ecologically important traits reflect
      evolutionary divergence? The use of phylogenetic diversity (PD) to predict
      biodiversity effects on ecosystem functioning, and more generally the use of
      phylogenetic information in community ecology, depends in part on the answer to
      this question. However, comparisons of the predictive power of phylogenetic
      diversity and functional diversity (FD) have not been conducted across a range of
      experiments. To address how phylogenetic diversity and functional trait variation
      control biodiversity effects on biomass production, we summarized the results of
      29 grassland plant experiments where both the phylogeny of plant species used in
      the experiments is well described and where extensive trait data are available.
      Functional trait variation was only partially related to phylogenetic distances
      between species, and the resulting FD values therefore correlate only partially
      with PD. Despite these differences, FD and PD predicted biodiversity effects
      across all experiments with similar strength, including in subsets that excluded
      plots with legumes and that focused on fertilization experiments. Two- and three
      trait combinations of the five traits used here (leaf nitrogen percentage,
      height, specific root length, leaf mass per unit area, and nitrogen fixation)
      resulted in the FD values with the greatest predictive power. Both PD and FD can
      be valuable predictors of the effect of biodiversity on ecosystem functioning,
      which suggests that a focus on both community trait diversity and evolutionary
      history can improve understanding of the consequences of biodiversity loss.

PMID- 21905425
TI  - The community effects of phenotypic and genetic variation within a predator
      population.
AB  - Natural populations are heterogeneous mixtures of individuals differing in
      physiology, morphology, and behavior. Despite the ubiquity of phenotypic
      variation within natural populations, its effects on the dynamics of ecological
      communities are not well understood. Here, we use a quantitative genetics
      framework to examine how phenotypic variation in a predator affects the outcome
      of apparent competition between its two prey species. Classical apparent
      competition theory predicts that prey have reciprocally negative effects on each
      other. The addition of phenotypic trait variation in predation can marginalize
      these negative effects, mediate coexistence, or generate positive indirect
      effects between the prey species. Long-term coexistence or facilitation, however,
      can be preceded by long transients of extinction risk whenever the heritability
      of phenotypic variation is low. Greater heritability can circumvent these
      ecological transients but also can generate oscillatory and chaotic dynamics.
      These dramatic changes in ecological outcomes, in the sign of indirect effects,
      and in stability suggest that studies which ignore intraspecific trait variation
      may reach fundamentally incorrect conclusions regarding ecological dynamics.

PMID- 21905426
TI  - The relative importance of host-plant genetic diversity in structuring the
      associated herbivore community.
AB  - Recent studies suggest that intraspecific genetic diversity in one species may
      leave a substantial imprint on the surrounding community and ecosystem. Here, we
      test the hypothesis that genetic diversity within host-plant patches translates
      into consistent and ecologically important changes in the associated herbivore
      community. More specifically, we use potted, grafted oak saplings to construct 41
      patches of four saplings each, with one, two, or four tree genotypes represented
      among the host plants. These patches were divided among two common gardens.
      Focusing first at the level of individual trees, we assess how tree-specific
      genotypic identity, patch-level genetic diversity, garden-level environmental
      variation, and their interactions affect the structure of the herbivore
      community. At the level of host-plant patches, we analyze whether the joint
      responses of herbivore species to environmental variation and genetic diversity
      result in differences in species diversity among tree quartets. Strikingly, both
      species-specific abundances and species diversity varied substantially among host
      tree genotypes, among common gardens, and among specific locations within
      individual gardens. In contrast, the genetic diversity of the patch left a
      detectable imprint on local abundances of only two herbivore taxa. In both cases,
      the effect of genetic diversity was inconsistent among gardens and among host
      plant genotypes. While the insect community differed significantly among
      individual host-plant genotypes, there were no interactive effects of the number
      of different genotypes within the patch. Overall, additive effects of
      intraspecific genetic diversity of the host plant explained a similar or lower
      proportion (7-10%) of variation in herbivore species diversity than did variation
      among common gardens. Combined with the few previous studies published to date,
      our study suggests that the impact of host-plant genetic diversity on the
      herbivore community can range from none to nonadditive, is generally low, and
      reaches its most pronounced impact at small spatial scales. Overall, our findings
      strengthen the emerging view that the impacts of genetic diversity are system,
      scale, and context dependent. As the next step in community genetics, we should
      then start asking not only whether genetic diversity matters, but under what
      circumstances its imprint is accentuated.

PMID- 21905427
TI  - Genotypic richness and phenotypic dissimilarity enhance population performance.
AB  - Increases in biodiversity can result from an increase in species richness, as
      well as from a higher genetic diversity within species. Intraspecific genetic
      diversity, measured as the number of genotypes, can enhance plant primary
      productivity and have cascading effects at higher trophic levels, such as an
      increase in herbivore and predator richness. The positive effects of genotypic
      mixtures are not only determined by additive effects, but also by interactions
      among genotypes, such as facilitation or inhibition. However, so far there has
      been no effort to predict the extent of such effects. In this study, we address
      the question of whether the magnitude of the effect of genotype number on
      population performance can be explained by the extent of dissimilarity in key
      traits among genotypes in a mixture. We examine the relative contribution of
      genotype number and phenotypic dissimilarity among genotypes to population
      performance of the soil arthropod, Orchesella cincta. Nearly homogeneous
      genotypes were created from inbred isofemale lines. Phenotypic dissimilarity
      among genotypes was assessed in terms of three life-history traits that are
      associated with population growth rate, i.e., egg size, egg development time, and
      juvenile growth rate. A microcosm experiment with genotype mixtures consisting of
      one, two, four, and eight genotypes, showed that genotypic richness strongly
      increased population size and biomass production and was associated with greater
      net diversity effects. Most importantly, there was a positive log-linear
      relationship between phenotypic dissimilarity in a mixture and the net diversity
      effects for juvenile population size and total biomass. In other words, the
      degree of phenotypic dissimilarity among genotypes determined the magnitude of
      the genotypic richness effect, although this relationship leveled off at higher
      values of phenotypic dissimilarity. Although the exact mechanisms responsible for
      these effects are currently unknown, similar advantages of trait dissimilarity
      have been found among species. Hence, to better understand population
      performance, genotype number and phenotypic dissimilarity should be considered
      collectively.

PMID- 21905428
TI  - Potassium, phosphorus, or nitrogen limit root allocation, tree growth, or litter
      production in a lowland tropical forest.
AB  - We maintained a factorial nitrogen (N), phosphorus (P), and potassium (K)
      addition experiment for 11 years in a humid lowland forest growing on a
      relatively fertile soil in Panama to evaluate potential nutrient limitation of
      tree growth rates, fine-litter production, and fine-root biomass. We replicated
      the eight factorial treatments four times using 32 plots of 40 x 40 m each. The
      addition of K was associated with significant decreases in stand-level fine-root
      biomass and, in a companion study of seedlings, decreases in allocation to roots
      and increases in height growth rates. The addition of K and N together was
      associated with significant increases in growth rates of saplings and poles (1-10
      cm in diameter at breast height) and a further marginally significant decrease in
      stand-level fine-root biomass. The addition of P was associated with a marginally
      significant (P = 0.058) increase in fine-litter production that was consistent
      across all litter fractions. Our experiment provides evidence that N, P, and K
      all limit forest plants growing on a relatively fertile soil in the lowland
      tropics, with the strongest evidence for limitation by K among seedlings,
      saplings, and poles.

PMID- 21905429
TI  - Cryptic herbivores mediate the strength and form of ungulate impacts on a long
      lived savanna tree.
AB  - Plant populations are regulated by a diverse array of herbivores that impose
      demographic filters throughout their life cycle. Few studies, however,
      simultaneously quantify the impacts of multiple herbivore guilds on the lifetime
      performance or population growth rate of plants. In African savannas, large
      ungulates (such as elephants) are widely regarded as important drivers of woody
      plant population dynamics, while the potential impacts of smaller, more cryptic
      herbivores (such as rodents) have largely been ignored. We combined a large-scale
      ungulate exclusion experiment with a five-year manipulation of rodent densities
      to quantify the impacts of three herbivore guilds (wild ungulates, domestic
      cattle, and rodents) on all life stages of a widespread savanna tree. We utilized
      demographic modeling to reveal the overall role of each guild in regulating tree
      population dynamics, and to elucidate the importance of different demographic
      hurdles in driving population growth under contrasting consumer communities. We
      found that wild ungulates dramatically reduced population growth, shifting the
      population trajectory from increase to decline, but that the mechanisms driving
      these effects were strongly mediated by rodents. The impact of wild ungulates on
      population growth was predominantly driven by their negative effect on tree
      reproduction when rodents were excluded, and on adult tree survival when rodents
      were present. By limiting seedling survival, rodents also reduced population
      growth; however, this effect was strongly dampened where wild ungulates were
      present. We suggest that these complex interactions between disparate consumer
      guilds can have important consequences for the population demography of long
      lived species, and that the effects of a single consumer group are often likely
      to vary dramatically depending on the larger community in which interactions are
      embedded.

PMID- 21905430
TI  - Terrestrial vertebrates alter seedling composition and richness but not diversity
      in an Australian tropical rain forest.
AB  - Although birds and mammals play important roles in several mechanisms
      hypothesized to maintain plant diversity in species-rich habitats, there have
      been few long-term, community-level tests of their importance. We excluded
      terrestrial birds and mammals from fourteen 6 x 7.5 m plots in Australian primary
      tropical rain forest and compared recruitment and survival of tree seedlings
      annually over the subsequent seven years to that on nearby open plots. We re
      censused a subset of the plots after 13 years of vertebrate exclusion to test for
      longer-term effects. After two years of exclusion, seedling abundance was
      significantly higher (74%) on exclosure plots and remained so at each subsequent
      census. Richness was significantly higher on exclosure plots from 1998 to 2003,
      but in 2009 richness no longer differed, and rarefied species richness was higher
      in the presence of vertebrates. Shannon's diversity and Pielou's evenness did not
      differ in any year. Vertebrates marginally increased density-dependent mortality
      and recruitment limitation, but neither effect was great enough to increase
      richness or diversity on open plots relative to exclosure plots. Terrestrial
      vertebrates significantly altered seedling community composition, having
      particularly strong impacts on members of the Lauraceae. Overall, our results
      highlight that interactions between terrestrial vertebrates and tropical tree
      recruitment may not translate into strong community-level effects on diversity,
      especially over the short-term, despite significant impacts on individual species
      that result in altered species composition.

PMID- 21905431
TI  - Inferring ecological and behavioral drivers of African elephant movement using a
      linear filtering approach.
AB  - Understanding the environmental factors influencing animal movements is
      fundamental to theoretical and applied research in the field of movement ecology.
      Studies relating fine-scale movement paths to spatiotemporally structured
      landscape data, such as vegetation productivity or human activity, are
      particularly lacking despite the obvious importance of such information to
      understanding drivers of animal movement. In part, this may be because few
      approaches provide the sophistication to characterize the complexity of movement
      behavior and relate it to diverse, varying environmental stimuli. We overcame
      this hurdle by applying, for the first time to an ecological question, a finite
      impulse-response signal-filtering approach to identify human and natural
      environmental drivers of movements of 13 free-ranging African elephants
      (Loxodonta africana) from distinct social groups collected over seven years. A
      minimum mean-square error (MMSE) estimation criterion allowed comparison of the
      predictive power of landscape and ecological model inputs. We showed that a
      filter combining vegetation dynamics, human and physical landscape features, and
      previous movement outperformed simpler filter structures, indicating the
      importance of both dynamic and static landscape features, as well as habit, on
      movement decisions taken by elephants. Elephant responses to vegetation
      productivity indices were not uniform in time or space, indicating that elephant
      foraging strategies are more complex than simply gravitation toward areas of high
      productivity. Predictions were most frequently inaccurate outside protected area
      boundaries near human settlements, suggesting that human activity disrupts
      typical elephant movement behavior. Successful management strategies at the human
      elephant interface, therefore, are likely to be context specific and dynamic.
      Signal processing provides a promising approach for elucidating environmental
      factors that drive animal movements over large time and spatial scales.

PMID- 21905432
TI  - Stochastic population dynamics in populations of western terrestrial garter
      snakes with divergent life histories.
AB  - Comparative evaluations of population dynamics in species with temporal and
      spatial variation in life-history traits are rare because they require long-term
      demographic time series from multiple populations. We present such an analysis
      using demographic data collected during the interval 1978-1996 for six
      populations of western terrestrial garter snakes (Thamnophis elegans) from two
      evolutionarily divergent ecotypes. Three replicate populations from a slow-living
      ecotype, found in mountain meadows of northeastern California, were characterized
      by individuals that develop slowly, mature late, reproduce infrequently with
      small reproductive effort, and live longer than individuals of three populations
      of a fast-living ecotype found at lakeshore locales. We constructed matrix
      population models for each of the populations based on 8-13 years of data per
      population and analyzed both deterministic dynamics based on mean annual vital
      rates and stochastic dynamics incorporating annual variation in vital rates. (1)
      Contributions of highly variable vital rates to fitness (lambda(s)) were buffered
      against the negative effects of stochastic variation, and this relationship was
      consistent with differences between the meadow (M-slow) and lakeshore (L-fast)
      ecotypes. (2) Annual variation in the proportion of gravid females had the
      greatest negative effect among all vital rates on lambda(s). The magnitude of
      variation in the proportion of gravid females and its effect on lambda(s) was
      greater in M-slow than L-fast populations. (3) Variation in the proportion of
      gravid females, in turn, depended on annual variation in prey availability, and
      its effect on lambda(s) was 4 23 times greater in M-slow than L-fast populations.
      In addition to differences in stochastic dynamics between ecotypes, we also found
      higher mean mortality rates across all age classes in the L-fast populations. Our
      results suggest that both deterministic and stochastic selective forces have
      affected the evolution of divergent life-history traits in the two ecotypes,
      which, in turn, affect population dynamics. M-slow populations have evolved life
      history traits that buffer fitness against direct effects of variation in
      reproduction and that spread lifetime reproduction across a greater number of
      reproductive bouts. These results highlight the importance of long-term
      demographic and environmental monitoring and of incorporating temporal dynamics
      into empirical studies of life-history evolution.

PMID- 21905433
TI  - Nonparametric spatial regression of survival probability: visualization of
      population sinks in Eurasian woodcock.
AB  - Both evolutionary ecologists and wildlife managers make inference based on how
      fitness and demography vary in space. Spatial variation in survival can be
      difficult to assess in the wild because (1) multisite study designs are not well
      suited to populations that are continuously distributed across a large area and
      (2) available statistical models accounting for detectability less than 1.0 do
      not easily cope with geographical coordinates. Here we use penalized splines
      within a Bayesian state-space modeling framework to estimate and visualize
      survival probability in two dimensions. The approach is flexible in that no
      parametric form for the relationship between survival and coordinates need be
      specified a priori. To illustrate our method, we study a game species, the
      Eurasian Woodcock Scolopax rusticola, based on band recovery data (5000
      individuals) collected over a > 50 000-km2 area in west-central France with
      contrasted habitats and hunting pressures. We find that spatial variation in
      survival probability matches an index of hunting pressure and creates a mosaic of
      population sources and sinks. Such analyses could provide guidance concerning the
      spatial management of hunting intensity or could be used to identify pathways of
      spatial variation in fitness, for example, to study adaptation to changing
      landscape and climate.

PMID- 21905434
TI  - Synergistic influences of phase, density, and climatic variation on the dynamics
      of fluctuating populations.
AB  - Although ecologists have long recognized that certain mammalian species exhibit
      high-amplitude, often multiannual, fluctuations in abundance, their causes have
      remained poorly understood and the subject of intense debate. A key contention
      has been the relative role of density-dependent and density-independent processes
      in governing population dynamics. We applied capture-mark-recapture analysis to
      25 years of monthly trapping data from a fluctuating prairie vole Microtus
      ochrogaster population in Illinois, USA, to estimate realized population growth
      rates and associated vital rates (survival and recruitment) and modeled them as a
      function of vole density and density-independent climatic variation. We also
      tested for phase dependence and seasonality in the effects of the above
      processes. Variation in the realized population growth rate was best explained by
      phase-specific changes in vole density lagged by one month and mean monthly
      temperatures with no time lags. The underlying vital rates, survival and
      recruitment, were influenced by the additive and interactive effects of phase,
      vole density, and mean monthly temperatures. Our results are consistent with the
      observation that large-scale population fluctuations are characterized by phase
      specific changes in demographic and physiological characteristics. Our findings
      also support the growing realization that the interaction between climatic
      variables and density-dependent factors may be a widespread phenomenon, and they
      suggest that the direction and magnitude of such interactive effects may be phase
      specific. We conclude that density-dependent and density-independent climatic
      variables work in tandem during each phase of density fluctuations to drive the
      dynamics of fluctuating populations.

PMID- 21905435
TI  - Chromosomal plasticity: mitigating the impacts of herbivory.
AB  - Endoreduplication, the replication of the genome without mitosis, leads to
      endopolyploidy, an increase in cellular chromosome number. Although
      endoreduplication is widespread among angiosperms and other groups of eukaryotes,
      the degree to which this process is plastic under varying environmental
      conditions and its potential adaptive significance are not known. Here, using
      flow cytometry, we measured plasticity in chromosome number following the removal
      of apical dominance (simulating natural herbivory) in two ecotypes of Arabidopsis
      thaliana: Columbia and Landsberg erecta. We report that endopolyploidy of clipped
      Columbia plants was significantly different than unclipped controls following the
      removal of apical dominance and regrowth, and that cellular ploidy is positively
      associated with attributes of fitness (biomass, flower, fruit, and seed
      production). In contrast, clipped Landsberg erecta showed no significant
      differences in endopolyploidy and a decrease in seed production compared to
      unclipped controls; representing a significant genotype x environment interaction
      between ecotypes. Altering ploidy via endoreduplication adds a previously unknown
      way in which plants may be able to cope with environmental stress: enhancing
      regrowth rates and fitness following plant damage.

PMID- 21905436
TI  - Sampling rate and misidentification of Levy and non-Levy movement paths: comment.

PMID- 21905437
TI  - Is it really affordable care?

PMID- 21905438
TI  - AMA focuses on graduate education requirements.
AB  - One Heart of America Caucus member was appalled when he learned that as an
      employed physician his new contract discouraged him from patient advocacy, as
      well as advocacy on behalf of physicians and his community.

PMID- 21905439
TI  - He who walks into walls.

PMID- 21905440
TI  - Saint Louis University Center for Abdominal Transplantation: 'show me' world
      class care.

PMID- 21905442
TI  - Role of interventional nephrology in dialysis access management.
AB  - Interventional nephrology is an area of medicine under the subspecialty of
      nephrology that provides improved vascular access care for dialysis patients.
      Since vascular access issues are a major cause of hospitalization in dialysis
      patients, interventional nephrologists help reduce hospitalization rates and
      costs, providing focused and economical medical care. A case has been presented
      at the end that highlights some management principles of vascular accesses. We
      also present a comprehensive review of recent data regarding trends in dialysis
      access management.

PMID- 21905441
TI  - New therapies for hepatitis C virus infection.
AB  - An estimated 170 million people in the world are infected with hepatitis C virus
      (HCV). These individuals are at risk for developing complications like cirrhosis
      and/or hepatocellular carcinoma. Occurrence of HCV has been recorded to be high
      in certain parts of the world like Africa and Southeast Asia. The prevalence is
      considerably lower in the United States, with an estimated number of people with
      positive HCV antibodies around 1.8% of the population and an estimated 3.1
      million individuals having active HCV infection. Treatment of hepatitis C has
      undergone a complete overhaul several times over the past decade and continues to
      evolve striving for constant improvement. We now are at the cusp of yet another
      such overhaul with the protease inhibitors about to be introduced into the
      market.

PMID- 21905443
TI  - Management of hepatocellular carcinoma: treatment options and indications for
      orthotopic liver transplantation.
AB  - Hepatocellular carcinoma (HCC) is the most common tumor worldwide and the leading
      cause of death amongst patients with cirrhosis. There are an estimated 500,000 or
      more new cases diagnosed each year in the world, with recent data suggesting an
      increase in incidence in the United State. Since the majority of HCC occurs in
      the setting of cirrhosis, an effective protocol for treatment needs to be in
      place addressing both management of underlying cirrhosis and cancer.

PMID- 21905444
TI  - Opportunities and challenges of expanded criteria organs in liver and kidney
      transplantation as a response to organ shortage.
AB  - In 1989, there were 19,000 patients on the UNOS (United Network of Organ Sharing)
      wait list for organs compared to 110,000 today. Without an equivalent increase in
      donors, the patients awaiting these organs for transplant face increasing
      severity of illness and risk of dying without receiving a transplant. This
      disparity in supply and demand has led to acceptance of organs with lower than
      expected success rates compared to previous standard donors variously defined as
      extended criteria donors in order to increase transplantation. The reluctance to
      wider use of these types of organs is based on the less than expected transplant
      center graft and patient survival results associated with their use, as well as
      the increased resources required to care for the patients who receive these
      organs. The benefits need to be compared to the survival of not receiving a
      transplant and remaining on the waiting list rather than on outcomes of receiving
      a standard donor. A lack of a systematic risk outcomes adjustment is one of the
      most important factors preventing more extensive utilization as transplant
      centers are held to patient and graft survival statistics as a performance
      measure by multiple regulatory organizations and insurers. Newer classification
      systems of such donors may allow a more systematic approach to analyzing the
      specific risks to individualized patients. Due to changes in donor policies
      across the country, there has been an increase in Extended Criteria Donors (ECD)
      organs procured by organ procurement organizations (OPO) but their uneven
      acceptance by the transplant centers has contributed to an increase in discards
      and organs not being used. This is one of the reasons that wider sharing of
      organs is currently receiving much attention. Transplanting ECD organs presents
      unique challenges and innovative approaches to achieve satisfactory results.
      Improved logistics and information technology combined strategies for improving
      donor quality with may prevent discards while insuring maximal benefit.
      Transplant centers, organ procurement organizations, third party payers and
      government agencies all must be involved in maximizing the potential for ECD
      organs.

PMID- 21905445
TI  - The economic impact of addressing the organ shortage with clinically high-risk
      allografts.
AB  - Expanding gaps between the number of patients awaiting transplantation and the
      number who receive organs in the United States has been associated with
      heightened disease severity among transplant candidates and more common use of
      organs from non-standard donors. We summarize data on the economic consequences
      of liver and renal allograft quality in contemporary practice. Policy makers and
      providers must work together to ensure that financial disincentives do not lead
      to wastage of lifesaving organs.

PMID- 21905446
TI  - High prevalence of iatrogenic hyperthyroidism in elderly patients with atrial
      fibrillation in an anticoagulation clinic.
AB  - In elderly patients with established atrial fibrillation (AF) who are receiving
      thyroid replacement, regular testing for thyroid function is often not performed,
      placing the patient at risk for iatrogenic hyperthyroidism. Of 215 patients
      followed in an anticoagulation clinic, 41 were receiving thyroid replacement and
      15 of these were found to have hyperthyroidism. Eight had documented AF
      coincident with abnormal thyroid function. In addition, only 22 patients on
      thyroid replacement had an annual TSH. In conclusion, iatrogenic hyperthyroidism
      may frequently be missed in AF patients because of inadequate monitoring of serum
      TSH. Thyroid replacement is common in elderly patients with AF followed in an
      anticoagulation clinic. Laboratory evidence of hyperthyroidism occurred in 37%,
      usually in patients with higher doses of thyroid replacement, and often
      associated with AF. The frequency of iatrogenic hyperthyroidism may be
      underestimated in patients with AF since many patients who receive thyroid
      replacement therapy are not monitored regularly with serum TSH.

PMID- 21905447
TI  - Rehabilitation of stroke: a new horizon.
AB  - Strokes are a leading cause of death and disability in the U.S. Comprehensive
      rehabilitation is needed to minimize disability. Theories that serve as a basis
      for recovery following stroke and therapeutic techniques used to potentiate
      recovery are discussed. Neuroplasticity is the potential for change in brain
      function. Functional brain images with positron emission tomography (PET),
      functional MRI (fMRI) and transcranial magnetic stimulation (TMS) have documented
      cortical reorganization in patients with partial or complete recovery following
      stroke. Therapeutic techniques with constraint induced movement therapy, body
      weight-supported treadmill training, and therapeutic electrical stimulation are
      reviewed.

PMID- 21905448
TI  - Glioblastoma. Part II: Future directions.
AB  - Although uncommon, "brain cancer" is one of the most feared diseases that afflict
      human beings. While still regarded as one of the most deadly forms of primary
      malignant brain neoplasm, recent advances in the treatment of Glioblastoma
      Multiforme (GBM) have offered new hope for patients, families and clinicians. In
      the first part of this two-part evidence-based review, we focused on the
      multidisciplinary advances that have established the current standard of care
      practice in the management of GBM. The second part discusses ongoing research
      efforts, both ongoing clinical trial efforts as well as some of the newer
      technologies that are forming the promise of the future.

PMID- 21905449
TI  - Grinding it out: wavefront spectacle lens in clinical practice.
AB  - This is the first literature report of a series of Zeiss iScription process wave
      guided spectacles (glasses) compared with conventional non-wave guided glasses.
      We designed a prospective pilot study of our initial clinical experience. Fifty
      patients with wavefront and fifty non-wavefront glasses were compared for lens
      changes made for comfort or visual clarity after initial manufacture and fitting.
      Minimum follow up was 90 days. Forty-six (92%) of the wavefront glasses required
      no modifications after initial delivery compared to 42 (86%) of non-wavefront
      glasses. There was a trend for conventional glasses to be returned more often
      than wavefront glasses but the difference was not statistically significant.

PMID- 21905450
TI  - PTSD: diagnosis, evolution, and treatment of combat-related
      psychological/psychiatric injury.
AB  - The long Iraq and Afghanistan conflicts have thrust Combat Related Post-Traumatic
      Stress Disorder (CR-PTSD) into the public consciousness and promoted national
      dialogue on the incidence and results of war related psychological trauma. In the
      first of a two part series we outline our contemporary understanding of CR-PTSD,
      the evolution of the diagnosis throughout the history of modern warfare, its
      impact on the mind and body, and its treatment. PTSD has become the mental health
      issue of our time.

PMID- 21905452
TI  - Climate change and infectious diseases in New Zealand: a brief review and
      tentative research agenda.
AB  - AIMS: To review the literature on infectious diseases and meteorological and
      climate change risk factors in the New Zealand context and to describe a
      tentative research agenda for future work. METHODS: We performed literature
      searches in May 2010 using Medline and Google Scholar. We also searched five
      health-related government agencies in New Zealand for documentation on climate
      change and health. RESULTS: The effect of climate variability and change on
      vector-borne disease has been considered in more detail than any other infectious
      disease topic (n=20+ journal articles and reports relating to New Zealand).
      Generally, concern has arisen around the risk of new mosquito incursions and
      increased risks of dengue and Ross River fevers in the long term. For enteric
      diseases, the picture from five New Zealand publications is somewhat mixed,
      although the data indicate that salmonellosis notifications increase with higher
      monthly temperatures. One interpretation of the New Zealand data is that
      communities without reticulated water supplies could be more vulnerable to the
      effects of climate change-mediated increases in protozoan diseases. This
      information informed a tentative research agenda to address research gaps.
      Priorities include the need for further work on a more integrated surveillance
      framework, vector-borne diseases, enteric diseases, skin infections, and then
      work on topics for which we found no published New Zealand work (such as
      influenza and leptospirosis). Finally, we found that health-related government
      agencies in New Zealand have relatively little 'climate change and health'
      information on their websites. CONCLUSIONS: Although some informative work has
      been done to date, much scope remains for additional research and planning to
      facilitate prevention, mitigation, and adaptation responses in the New Zealand
      setting around climate change and infectious disease risks. The tentative
      research agenda produced could benefit from a wider critique, and government
      agencies in New Zealand could contribute to informed discussions by better
      documenting the current state of knowledge on their websites.

PMID- 21905451
TI  - Exploring the molecular mechanisms of nickel-induced genotoxicity and
      carcinogenicity: a literature review.
AB  - Nickel, a naturally occurring element that exists in various mineral forms, is
      mainly found in soil and sediment, and its mobilization is influenced by the
      physicochemical properties of the soil. Industrial sources of nickel include
      metallurgical processes such as electroplating, alloy production, stainless
      steel, and nickel-cadmium batteries. Nickel industries, oil- and coal-burning
      power plants, and trash incinerators have been implicated in its release into the
      environment. In humans, nickel toxicity is influenced by the route of exposure,
      dose, and solubility of the nickel compound. Lung inhalation is the major route
      of exposure for nickel-induced toxicity. Nickel can also be ingested or absorbed
      through the skin. The primary target organs are the kidneys and lungs. Other
      organs such as the liver, spleen, heart, and testes can also be affected to a
      lesser extent. Although the most common health effect is an allergic reaction,
      research has also demonstrated that nickel is carcinogenic to humans. The focus
      of the present review is on recent research concerning the molecular mechanisms
      of nickel-induced genotoxicity and carcinogenicity. We first present a background
      on the occurrence of nickel in the environment, human exposure, and human health
      effects.

PMID- 21905453
TI  - Impact of ammunition and military explosives on human health and the environment.
AB  - OBJECTIVE: To review the literature concerning the risks associated with the main
      xenobiotics contained in military ammunition and explosive residues and damage to
      human and environmental health. METHODOLOGY: Using "ammunition", "military",
      "environmental", "health", "explosive", "metal", "TNT", "RDX", "pollution", and
      "contamination" as search terms, a large database, namely ISI Web of Knowledge
      and PubMed, was searched for studies on military ammunition and explosive
      residues from 1989 to 2010. Other sources used to conduct the search included the
      library of the Toxicology Laboratory of the Center for Workers' Health and Human
      Ecology (CESTEH) at the National School of Public Health. RESULTS: In total, 15
      different combinations were used with the search words above and 708 papers were
      found. Among them, 76 papers concerned this review. More than 12 references of
      interest were discovered in the library of the CESTEH. The results were organized
      into metals, dinitrotoluene, trinitrotoluene (TNT), and royal demolition
      explosive (RDX), showing their main uses, occurrence in the environment, the
      current toxic effects to human and environmental health, and remediation
      possibilities. CONCLUSION: Because military activities can cause the acute and
      chronic exposure of human beings, the public administration must aim politics
      towards suitable environmental management.

PMID- 21905454
TI  - The value of ecologic studies: mercury concentration in ambient air and the risk
      of autism.
AB  - Ecologic studies of the spatial relationship between disease and sources of
      environmental contamination can help to ascertain the degree of risk to
      populations from contamination and to inform legislation to ameliorate the risk.
      Population risks associated with persistent low-level mercury exposure have
      recently begun to be of concern and current reports implicate environmental
      mercury as a potential contributor in the etiology of various developmental and
      neurodegenerative diseases including autism and Alzheimer's disease. In this
      demonstration of preliminary findings, we demonstrate for Bexar County Texas and
      Santa Clara County California, the hypothesis that the spatial structure of the
      occurrence of autism has a positive co-variation with the spatial structure of
      the distribution of mercury in ambient air. The relative risk of autism is
      greater in the geographic areas of higher levels of ambient mercury. We find that
      the higher levels of ambient mercury are geographically associated with point
      sources of mercury emission, such as coal-fired power plants and cement plants
      with coal-fired kilns. Although this does not indicate a cause, these results
      should not be dismissed, but rather seen as a preliminary step for generating a
      hypothesis for further investigation.

PMID- 21905455
TI  - Methodological lessons and pilot data on the effect of proximity of homes and
      schools to highways on pediatric asthma and lung function.
AB  - PURPOSE: Numerous studies have found that either living or attending school near
      highways or exposure to pollutants associated with heavy motor vehicle traffic
      are associated with a high prevalence of asthma and reduced lung function. Yet,
      few investigations have assessed school and home exposure in the same study.
      METHODS: We recruited children aged 5-19 years from a pediatric clinic in an
      urban center (Boston Chinatown) for many of whom housing and school were located
      immediately adjacent to two major highways. A questionnaire was used to assess
      self-report of diagnosis of asthma and the proximity of schools and homes to
      highways, as well as basic demographic information. Spirometric lung function
      data were obtained and reviewed by a pediatric pulmonologist blinded to survey
      responses. During this review, we excluded lung function tests of low quality.
      RESULTS: The analyses did not demonstrate any associations or mean differences
      between near-highway exposure at school, at home, or both with diagnosed asthma
      (p>0.10, n=124). For the lung function data (n=87), neither direct measures
      (FEV1, FVC, and FEF(25-75)) nor ratio measures (FEV1/FVC and FEF(25-75)/FVC) had
      a significant association with near-highway exposure (p>0.10). Certain
      predisposing factors, such as diagnosed allergies and family history of asthma,
      were strongly associated with diagnosed asthma (p<0.05 and p=0.001,
      respectively), findings we have seen consistently in other work with children
      recruited from the same clinic. We also found that exposure to pests was
      significantly correlated with a smaller FEF(25-75)/FVC ratio (p=0.02).
      CONCLUSIONS: Our findings suggest that either limitations in our study design
      restricted our ability to see the associations reported by others or that such
      associations do not exist in this population. One possibility is that in this
      community, with heavy street traffic and many street canyons, the gradient of
      exposure next to the highway is not very well delineated by simple proximity.

PMID- 21905456
TI  - Environmental and demographic risk factors associated with the prevalence of
      Cryptosporidium infection in the Alice rural settlements of the Eastern Cape
      Province of South Africa: a pilot study.
AB  - We undertook this study to identify the risk factors and prevalence of
      Cryptosporidium spp. in HIV-positive and HIV-negative diarrhea patients in the
      Alice rural settlement in the Eastern Cape Province of South Africa. A total of
      180 stool specimens (35 HIV-positive diarrhea, 125 HIV-negative diarrhea
      patients, and 20 apparently healthy subjects) were screened for cryptosporidiosis
      using an ELISA-based approach. Sociodemographic information, water supply, and
      animal contact were recorded for diarrhea-positive patients. The data were
      analyzed using Pearson's chi2-test and Fisher's exact test. Cryptosporidium
      antigen was detected in 122 of 180 specimens (overall prevalence=67.8%). In HIV
      positive diarrhea patients, the age groups 31-43 years (mean age 36.5 years) and
      70-82 years (mean age 75.8 years) had a higher prevalence (100%) of the antigen
      than age groups 18-30 years (mean age 23.2 years) and 83-95 years (mean age 88.8
      years) (50.0%). In HIV-negative diarrhea patients, the prevalence was highest
      (87.5%) at ages 18-30 years (mean age 23.2 years) and lowest (35.7%) at ages 83
      95 years (mean age 88.8 years). Cryptosporidium antigenemia was slightly higher
      in females (78.2%, mean age 46.7 years) than in males (71.1%, mean age 42.6
      years), but the difference was not significant (p>0.05). No apparently healthy
      control subject was infected with Cryptosporidium. HIV-negative patients had a
      significantly higher prevalence of antigen than HIV-positive patients, with farm
      animals considered a possible risk factor. In HIV-positive diarrhea patients, the
      prevalence peak was detected in more low income patients (85.7%) than in high
      income patients (32%). The high infection rate of specific groups was associated
      with exposure to a contaminated water supply. The results indicate that
      Cryptosporidium infection is highly prevalent in adult fecal specimens from the
      Nkonkobe Municipality, an indication of active infection that is likely to emerge
      as a major human pathogen in this locality owing to socioeconomic changes that
      favor transmission.

PMID- 21905457
TI  - AAPA's new president: learn more about a man on a mission.

PMID- 21905458
TI  - Simvastatin dosing restrictions; monitoring amiodarone therapy.

PMID- 21905459
TI  - What caused the rash on this high school athlete?

PMID- 21905460
TI  - Childhood obesity: screening and early intervention.

PMID- 21905461
TI  - Laceration repair: avoid infection, optimize healing, minimize scarring.

PMID- 21905462
TI  - A rare cause of hip pain characterized by an inability to walk or bear weight.

PMID- 21905463
TI  - Hidden variables: why patients may misunderstand written screening tools.

PMID- 21905464
TI  - Abdominal compartment syndrome: potentially lethal and easy to miss.

PMID- 21905465
TI  - Ovarian cancer: breaking the silence.

PMID- 21905466
TI  - Can an ACE inhibitor reduce the risk of developing progressive renal disease?

PMID- 21905467
TI  - Quick recertification series. Cauda equina syndrome; acute respiratory distress
      syndrome.

PMID- 21905468
TI  - Can I be screened for ovarian cancer?

PMID- 21905469
TI  - Patient information. Can I be screened for ovarian cancer?

PMID- 21905470
TI  - A case of confabulation and abnormal eye movements.

PMID- 21905471
TI  - Preimplantation genetic diagnosis.

PMID- 21905472
TI  - Case of the month. Hereditary hemorrhagic telangiectasia.

PMID- 21905473
TI  - Offer a guiding hand.

PMID- 21905474
TI  - How far have we come?

PMID- 21905475
TI  - The art of self study.

PMID- 21905476
TI  - Is it time for hospice?

PMID- 21905477
TI  - Giving you what you want.

PMID- 21905478
TI  - Governance first, technology second to effective CPOE deployment: rapid
      development of order sets provides the foundation for CPOE, but healthcare
      organizations first need an effective governance plan built around clinician
      workflow.

PMID- 21905479
TI  - How to bridge the gulf between the front and back office: the answer may lie in
      the cloud.

PMID- 21905480
TI  - Enhancing nursing productivity through mobile computing solutions: mobile
      computing and medication solutions allow nurses more time at patient bedsides.

PMID- 21905481
TI  - Streamlining healthcare with multifunctional devices and advanced workflows:
      Healthcare providers generally face some of the most complex workflow hurdles of
      any industry.

PMID- 21905482
TI  - The elegance of workflow automation: improving workflow leads to a virtuous cycle
      of process enhancement.

PMID- 21905483
TI  - Preparing for tomorrow's challenges today, with automation: automation technology
      gives hospitals the ability to streamline processes, reduce costs, increase
      accuracy and ensure the deliverability of data from one system to another.

PMID- 21905484
TI  - In pursuit of EMR, Gastroenterology Associates of Cleveland upgrades disaster
      recovery (DR) operation: EMR implementation forces look at DR options.

PMID- 21905485
TI  - Get help planning a data center: Data center projects require extraordinary
      foresight and technical expertise. Get a few steps ahead of the game by following
      these recommendations.

PMID- 21905486
TI  - It's back to the future for storage of PACS images: the concept of a shared
      central repository has been a staple of information technology for decades.

PMID- 21905487
TI  - Gulf Coast Health Center serves its community with a new EMR system: GCHC needed
      a system with inherent flexibility that would allow for upgrades and expansion of
      the system as necessary.

PMID- 21905488
TI  - Just what the doctor ordered: giving the best care to your best patients.
      Measuring patient perceptions and gauging loyalty are key.

PMID- 21905489
TI  - We've got an app for that: using mobile technology to improve care management and
      drug adherence for at-risk patients.

PMID- 21905490
TI  - A new telecommunications solution enhances productivity and patient care:
      outdated system hampered productivity.

PMID- 21905491
TI  - Telepsychiatry in the cloud: reaching rural communities in underserved markets.

PMID- 21905492
TI  - What ICD-10 means for doctors: the 2013 coding update may lead to revenue loss if
      physicians are not prepared.

PMID- 21905493
TI  - Lean strategies reduce bottlenecks: achieving clinical automation through the use
      of a real-time locating system.

PMID- 21905494
TI  - "Our rotten dental care system: if you're poor, just grin and bear it...".

PMID- 21905495
TI  - The code. One dentist's thoughts on the importance of understanding the ADA code
      and how insurance companies' policies relate to the code.

PMID- 21905496
TI  - Consensus statement on the diagnosis, management, and treatment of angioedema
      mediated by bradykinin. Part I. Classification, epidemiology, pathophysiology,
      genetics, clinical symptoms, and diagnosis.
AB  - BACKGROUND: There are no Spanish guidelines or consensus statement on bradykinin
      induced angioedema. AIM: To review the pathophysiology, genetics, and clinical
      symptoms of the different types of bradykinin-induced angioedema and to draft a
      consensus statement in light of currently available scientific evidence and the
      experience of experts. This statement will serve as a guideline to health
      professionals. METHODS: The consensus was led by the Spanish Study Group on
      Bradykinin-Induced Angioedema (SGBA), a working group of the Spanish Society of
      Allergology and Clinical Immunology. A review was conducted of scientific papers
      on different types of bradykinin-induced angioedema (hereditary and acquired
      angioedema due to C1 inhibitor deficiency, hereditary angioedema related to
      estrogens, angioedema induced by angiotensin-converting enzyme inhibitors).
      Several discussion meetings of the SGBA were held in Madrid to reach the
      consensus. RESULTS: The pathophysiology, genetics, and clinical symptoms of the
      different types of angioedema are reviewed. Diagnostic approaches are discussed
      and the consensus reached is described. CONCLUSIONS: A review of bradykinin
      induced angioedema and a consensus on diagnosis are presented.

PMID- 21905497
TI  - Evaluation of CARMA1/CARD11 and Bob1 as candidate genes in common variable
      immunodeficiency.
AB  - BACKGROUND AND OBJECTIVE: The candidate gene approach has led to the detection of
      associations between common variable immunodeficiency (CVID) and mutations in the
      genes TACI, ICOS, BAFF-R, CD19, CD20, and CD81. Such mutations are present in
      less than 15% of cases, highlighting the complexity of the disease. Animal models
      for 2 genes involved in B-cell development, namely CARMA1/CARD11 and Bob1,
      develop an immunological phenotype similar to that seen in CVID, with low
      immunoglobulin serum levels, defective responses to antigen, and defective B-cell
      activation. The aim of this study was to evaluate CARMA1/CARD11 and Bob1 as
      candidate genes for the pathogenesis of CVID in a cohort of 66 patients with the
      disease. PATIENTS AND METHODS: We performed direct gene sequencing of
      CARMA1/CARD11 and Bob1 in 66 patients with CVID. RESULTS: Seven already reported
      genetic variants and 4 novel ones were found in the CARMA1/CARD11 gene, while 1
      already reported variant and 1 novel variant were found in the Bob1 gene.
      CONCLUSIONS: Although novel genetic variants were identified in both the
      CARMA1/CARD11 and the Bob1 gene, no disease-causing mutations were identified in
      our group of patients. However, 4 of the variants in CARMA1 and 1 of those in
      Bob1 were associated with the disease. Considering the heterogeneity and
      complexity of CVID, further studies are needed to better define the genetic
      mechanisms involved in the pathogenesis of the disease.

PMID- 21905498
TI  - Percutaneous application of peptidoglycan from Staphylococcus aureus induces
      infiltration of CCR4+ cells into mouse skin.
AB  - BACKGROUND: The lesional skin of patients with atopic dermatitis has an increased
      number of type 2 helper T (TH2) cells in the dermis and is superficially
      colonized by Staphylococcus aureus. The purpose of this study was to determine
      the effects of peptidoglycan (PEG) from S aureus on TH2 cell induction in murine
      skin. METHODS: Mice were sensitized with house dust mite antigen (MA) by topical
      application to barrier-disrupted abdominal skin. Seven days after sensitization,
      PEG was applied to the barrier-disrupted dorsal skin. After a further 3 days, C-C
      chemokine receptor type 4-positive (CCR4+) cells were counted in the PEG-treated
      skin.The production of chemokine (C-C) motif ligand 17 (CCL17) (thymus- and
      activation-regulated chemokine) and CCL22 (macrophage-derived chemokine) in the
      skin was investigated using reverse transcriptase polymerase chain reaction and
      immunohistological analysis. RESULTS: Application of PEG to the dorsal skin of MA
      sensitized mice led to a significant increase in the number of cells expressing
      CCR4 in the dermis. The skin of PEG-treated mice showed an increased level of
      CCL17 mRNA expression, which coincided with TH2 cytokine mRNA expression.
      Immunohistological analysis demonstrated that levels of CCL17 transcripts
      corresponded to those of protein synthesis in the epidermis. CCL17 production was
      induced mainly by Langerhans cells stimulated with PEG. Furthermore,
      intraperitoneal injection of anti-CCL17 antibody abrogated the induction of CCR4+
      cells in the skin. CONCLUSION: These results suggest that PEG may induce TH2
      cells in the skin through the production of CCL17 by Langerhans cells and would
      explain the role of colonization by S aureus in patients with atopic dermatitis.

PMID- 21905499
TI  - Clinical use of oral antihistamines and intranasal corticosteroids in patients
      with allergic rhinitis.
AB  - BACKGROUND: Second-generation oral antihistamines (AH) and intranasal
      corticosteroids (ICS) are the most widely used drugs for allergic rhinitis (AR).
      OBJECTIVE: To obtain information on the preferences for and applications of these
      drugs under conditions of routine clinical practice. METHODS: We performed a
      multicenter multidisciplinary observational study. Participating physicians
      completed a questionnaire with information on preferences for and application of
      drugs for AR, patient characteristics, and physician/patient satisfaction with
      the treatment provided (visual analog scale). RESULTS: A total of 1008 physicians
      participated in the study (primary care physicians, 53%; ear, nose, and throat
      specialists, 28%; allergologists, 19%). Treatment preferences in AR were AH
      combined with ICS (7.68), AH (7.25), and ICS (6.94). AH and ICS were used
      continuously by 58% and 71% of patients, respectively. Physicians reported having
      a good knowledge of the Allergic Rhinitis and its Impact on Asthma guidelines
      (93%), and 90% claimed to follow the guidelines. A total of 4040 patients were
      recruited (52% females, mean [SD] age 34 [14] years). The findings for AR were as
      follows: mean (SD) duration, 9 (8) years; persistent AR, 52%; mild AR, 72%;
      moderate AR, 7%; and severe AR, 1%. Patients considered the disorder to be well
      controlled/almost controlled (79%). As for treatment, 77% followed the regimen
      recommended by the physician. Oral treatment (41%) and intranasal treatment (22%)
      were preferred, while 35% showed no preference for any given administration
      route. The treatments prescribed were AH combined with ICS (66%), AH (20%), ICS
      (11%), other antihistamines (4%), and other drugs (6%). Combination treatment was
      the preferred therapy, regardless of the type of rhinitis. CONCLUSIONS:
      Physicians prefer and more often use combination treatment with oral AH and ICS,
      regardless of the frequency and intensity of AR.

PMID- 21905500
TI  - Polymorphisms in toll-like receptor 4 gene are associated with asthma severity
      but not susceptibility in a Chinese Han population.
AB  - BACKGROUND AND OBJECTIVES: The toll-like receptor 4 (TLR4) gene links human
      innate immunity and adaptive immunity via bacterial endotoxin recognition, and
      plays a considerable role in the pathogenesis of asthma. The effects of the
      genetic variants of TLR4 on asthma are still largely unknown. This study aimed to
      evaluate the effects of TLR4 polymorphisms on asthma risk and asthma-related
      phenotypes in a Chinese Han population. METHODS: We consecutively recruited 318
      unrelated adult asthmatic patients and 352 healthy volunteers. Four tagging
      single nucleotide polymorphisms (SNPs) in the TLR4 gene were detected using
      GenomeLab SNPstream or TaqMans Genotyping. We conducted case-control and case
      only studies to investigate the association between the selected tagging SNPs in
      TLR4 and asthma and asthma-related phenotypes. RESULTS: We found no evidence to
      support a significant association between TLR4 SNPs and asthma susceptibility.
      However, our results revealed that the TT homozygote of rs1927914 was associated
      with lower forced expiratory volume in the first second (percent predicted) in
      asthmatic patients. An evidently positive association was found between asthma
      severity and both the TT genotype of rs1927914 and the GG genotype of rs10983755
      and rs1927907 (P = .024, P = .009, and P = .013, respectively), indicating that
      the C allele of rs1927914 and the A allele of rs10983755 and rs1927907 have a
      protective effect on asthma severity. CONCLUSION: TLR4 polymorphisms do not
      contribute to asthma susceptibility but they may influence the severity of
      asthma.

PMID- 21905501
TI  - Variations in the STK10 gene and possible associations with aspirin-intolerant
      asthma in a Korean population.
AB  - BACKGROUND AND OBJECTIVE: Lymphocyte-oriented kinase deficiency encoded by the
      serine/threonine kinase 10 (STK10) gene correlates with the intracellular
      adhesion molecule 1 (ICAM-1)/lymphocyte function associated antigen 1 (LFA-1)
      complex in aspirin hypersensitivity. This study investigated the association
      between single nucleotide polymorphisms (SNPs) of STK10 and aspirin-intolerant
      asthma (AIA). METHODS: A total of 54 SNPs were genotyped in 163 AIA patients and
      429 aspirin-tolerant asthma (ATA) controls. RESULTS: Logistic regression revealed
      that a synonymous variant (rs2306961G>A) had the most significant association
      with AIA (P = .008 under the codominant model; P = .004 under the dominant
      model), suggesting that tissue-specific codon usage between Lys_TTT and Lys_CTT
      could play a role in regulating expression of STK10 in airway epithelium.
      Haplotype analysis revealed that 4 haplotypes, including STK10_BL4-ht1, which is
      unique to rs2306961G>A, were significantly associated with aspirin
      hypersensitivity in asthmatics (P < .05). CONCLUSIONS: Although replications in
      independent cohorts and further functional evaluations are needed, our
      preliminary findings suggest that STK10 polymorphisms might be susceptible
      genetic markers of AIA and that gene expression could be mediated by tissue
      specific codon usage.

PMID- 21905502
TI  - Autoimmunity and hepatitis A vaccine in children.
AB  - BACKGROUND: Universal vaccination remains the most effective way of preventing
      the spread of many infectious diseases. Although most adverse effects attributed
      to vaccines are mild, rare reactions such as autoimmunity do occur. OBJECTIVES:
      We aimed to evaluate the possible role played by hepatitis A vaccine (HAV) in
      inducing the synthesis of autoantibodies. The study included 40 healthy children
      vaccinated with 2 doses of HAV at a 6-month interval. The children were
      investigated for autoantibodies including anti-nuclear antibodies (ANAs), anti
      smooth muscle antibodies, anti-nDNA, anti-microsomal antibodies, anti-cardiolipin
      (aCL) immunoglobulin (Ig) M/IgG, anti-ds DNA, ANA profile, and anti-neutrophil
      cytoplasmic antibody profile. RESULTS: One month after the first dose, ANAs at a
      titer of 1:100 and aCL IgG at 23.7 IgM phospholipid units were detected in 4
      children and 1 child, respectively. Of the ANA-positive children, 1 also had ASMA
      positivity, and another had perinuclear and cytoplasmic ANCA positivity. After
      the second dose, 3 of the children had aCL IgM. In addition, 2 distinct children
      had positive anti-thyroid microsomal antibodies and ANA after the second dose.
      The presence of these autoantibodies following vaccination was statistically
      significant (P = .002). At month 12 of the study, only 2 children continued to be
      ANA-positive at the same titer as after the first vaccine dose. CONCLUSIONS:
      Although HAV can induce the production of autoantibodies, none of the children
      developed autoimmune disorders. Long-term follow up is necessary to check whether
      autoimmune disorders develop in children who still have ANA. Genetic,
      immunological, environmental, and hormonal factors are also important in the
      development of vaccine-induced autoimmunity.

PMID- 21905503
TI  - Promoter polymorphisms of the CD14 gene are associated with atopy in Pakistani
      adults.
AB  - BACKGROUND: Several studies have shown that promoter polymorphisms of the CD14
      gene are associated with atopic asthma. However, the results of association
      studies in different populations are conflicting. This study aimed to investigate
      the possible association between the CD14 polymorphisms A-1145G and C-159T and
      atopic phenotypes in Pakistani cohorts. METHODS: Healthy controls (n = 120) and
      atopic patients (n=220) were genotyped for the single-nucleotide polymorphisms C
      159T (rs2569190) and A-1145G (rs2569191) using restriction fragment length
      polymorphism-polymerase chain reaction. RESULTS: The genotype and allelic
      frequencies were in Hardy-Weinberg equilibrium. Overall, strong associations were
      observed between both C-159T (P = .02; chi2 = 7.16) and A-1145G (P = .01; chi =
      7.88) and atopy. The G allele of A-1145G was significantly associated with atopy
      (P < .009; chi2 = 6.72). When the data were stratified, the associations observed
      were due to the individual phenotypes: atopic asthma was significantly associated
      with A-1145G (P = .02; chi2 = 7.18), whereas the association between C-159T and
      atopy was attributed to patients with allergic rhinitis (P = .01; chi2 = 8.13).
      CONCLUSION: In Pakistani adults, the A-1145G polymorphism is associated with
      atopic asthma, whereas the C-159T polymorphism is significantly associated with
      allergic rhinitis.

PMID- 21905504
TI  - Phosphorylation reduces the allergenicity of cow casein in children with
      selective allergy to goat and sheep milk.
AB  - This study aimed to characterize the role of phosphorylation of caseins in
      selective allergy to goat milk (GM) and sheep milk (SM) in patients with good
      tolerance to cow milk (CM). We performed skin prick tests with milk and caseins
      from CM, GM, and SM and immunoblotting and specific immunoglobulin (Ig) E
      determinations with milk and casein from cow and GM and SM. Sensitization to milk
      and caseins from goat and sheep was demonstrated in all 3 patients by skin tests,
      determination of specific IgE, or both. Immunoblotting confirmed that GM/SM
      proteins but not CM proteins were involved in the allergic symptoms. IgE reacted
      with several protein bands from the caseins and milk extracts of both sheep and
      goat. Phosphorylation was involved in the different allergenicity of CM caseins.
      We report the implication of phosphorylation in the allergenicity of caseins
      involved in selective allergy to GM and SM.

PMID- 21905505
TI  - Bacille Calmette-Guerin lymphadenitis and recurrent oral candidiasis in an infant
      with a new mutation leading to interleukin-12 receptor beta-1 deficiency.
AB  - Mendelian susceptibility to mycobacterial diseases (MSMD) is a rare syndrome
      characterized by predisposition to infections caused by weakly virulent
      mycobacteria, such as those in bacille Calmette-Guerin (BCG) vaccine and
      environmental mycobacteria. Salmonellosis has been reported in almost half of
      affected patients. Patients are also vulnerable to Mycobacterium tuberculosis
      infection. Several other infectious diseases may occur, albeit rarely.
      Mucocutaneous candidiasis is more common. Interleukin-12 receptor beta1 (IL
      12Rbeta1) deficiency is the most frequent genetic cause of MSMD. Here, we
      describe an infant with a single episode of BCG lymphadenitis who also suffered
      from recurrent oral candidiasis. Genetic analysis revealed a new homozygous
      mutation (64+1G>T) in the IL12RB1 gene that caused complete IL-12R1beta1
      deficiency. IL-12Rbeta1 deficiency should be considered in patients with BCG
      infection, even in those who experience a single episode of BCG lymphadenitis or
      recurrent mucocutaneous candidiasis. Every attempt should be made to heighten
      awareness in countries where BCG vaccination is performed.

PMID- 21905507
TI  - Storage mites in flour samples in Wellington, New Zealand.

PMID- 21905508
TI  - An immediate hypersensitivity reaction caused by tolperisone hydrochloride.

PMID- 21905506
TI  - Membranous glomerulopathy in an adult patient with X-linked agammaglobulinemia
      receiving intravenous gammaglobulin.
AB  - BACKGROUND: Immune complex deposition in the subepithelial zone of glomerular
      capillaries can lead to membranous glomerulopathy. OBJECTIVE: To present the case
      of a 23-year-old man with X-linked agammaglobulinemia (XLA) who developed
      idiopathic membranous glomerulopathy while receiving intravenous immunoglobulin
      (IVIG). METHODS: We performed an immunological workup, genetic testing, and a
      renal biopsy. RESULTS: XLA was confirmed with less than 0.02% CD19+ cells in the
      blood after sequence analysis revealed a nonfunctional BTK gene. The patient
      presented with microhematuria, which persisted for 3 years and spanned treatment
      with 5 different preparations of intravenous gammaglobulin. Immunohistochemistry
      revealed membranous glomerulopathy. CONCLUSION: Although endogenous serum
      immunoglobulin (Ig) production is severely impaired in XLA, rare B lymphocytes
      that have managed to mature can produce functional IgG antibodies. The pathogenic
      immune complexes could reflect IVIG reacting with polymorphic autoantigens, an
      endogenous IgG-producing clone reacting with a common idiotype present in the
      IVIG, or both.

PMID- 21905509
TI  - Tracheomalacia: uncommon onset in a patient with severe asthma.

PMID- 21905510
TI  - A study of the variability of the in vitro component-based microarray ISAC CDR
      103 technique.

PMID- 21905511
TI  - Selective hypersensitivity with positive immediate skin tests to nimesulide.

PMID- 21905512
TI  - Omalizumab (an anti-IgE antibody) in the treatment of severe atopic eczema.

PMID- 21905513
TI  - A severe case of lipoatrophy due to human insulin and insulin analogs in a
      patient with diabetes: is an immunological mechanism involved?

PMID- 21905514
TI  - Fixed drug eruption due to meloxicam.

PMID- 21905515
TI  - Drug fever caused by eutectic mixture of local anesthetic cream.

PMID- 21905516
TI  - Social media: friend or foe?

PMID- 21905517
TI  - Making the most of meaningful use.

PMID- 21905518
TI  - Capital punishment.

PMID- 21905519
TI  - Starting from scratch.

PMID- 21905520
TI  - Hackers, breaches and other threats to electronic records.

PMID- 21905521
TI  - Doc connector. Interview by Elizabeth Gardner.

PMID- 21905522
TI  - Resting pulse rate reference data for children, adolescents, and adults: United
      States, 1999-2008.
AB  - OBJECTIVE: This report presents national reference data on resting pulse rate
      (RPR), for all ages of the U.S. population, from 1999-2008. METHODS: During 1999
      2008, 49,114 persons were examined. From this, a normative sample comprising
      35,302 persons was identified as those who did not have a current medical
      condition or use a medication that would affect the RPR. RPR was obtained after
      the participant had been seated and had rested quietly for approximately 4
      minutes. RESULTS: RPR is inversely associated with age. There is a mean RPR of
      129 beats per minute (standard error, or SE, 0.9) at less than age 1 year, which
      decreases to a mean RPR of 96 beats/min (SE 0.5) by age 5, and further decreases
      to 78 beats/min (SE 0.3) in early adolescence. The mean RPR in adulthood plateaus
      at 72 beats/min (SE 0.2) (p < 0.05 for trend). In addition, there is a
      significant gender difference, with the male pulse rate plateauing in early
      adulthood, while the female resting pulse plateaus later when middle-aged. There
      are two exceptions, that is, infants under age 1 year and adults aged 80 and
      over, when the mean RPR is statistically and significantly higher in females than
      in males (females under age 20 have an RPR of 90 beats/min, SE 0.3, and males
      under age 20 have an RPR of 86 beats/min, SE 0.3, p <0.05; females aged 20 and
      over have an RPR of 74 beats/min, SE 0.2, and males aged 20 and over have an RPR
      of 71 beats/min, SE 0.3, p <0.05). After controlling for age effects, non
      Hispanic black males have a significantly (p <0.001) lower mean RPR (74
      beats/min) than non-Hispanic white males (77 beats/min) and Mexican-American
      males (76 beats/min). Among females, non-Hispanic black females (79 beats/min)
      and Mexican-American females (79 beats/min) had statistically and significantly
      (p < 0.01) lower mean RPRs compared with non-Hispanic white females (80
      beats/min). Among males, the prevalence of clinically defined tachycardia
      (abnormally fast heart rate, RPR 100 beats/min) is 1.3% (95% CI = 1.1-1.7), and
      the prevalence of clinically defined bradycardia (abnormally slow heart rate, RPR
      < 60 beats/min) is 15.2% (95% CI = 14.1-16.4). For adult females, these
      prevalences are 1.9% (95% CI = 1.6-2.3) for clinical tachycardia and 6.9% (95% CI
      = 6.2-7.8) for clinical bradycardia. Controlling for age, males have higher odds
      (2.43, 95% CI = 2.09-2.83) of having bradycardia, and notably lower odds (0.71,
      95% CI = 0.52-0.97) of having tachycardia than women. CONCLUSIONS: The data
      provides current, updated population-based percentiles of RPR, which is one of
      the key vital signs routinely measured in clinical practice.

PMID- 21905523
TI  - What would Scrib think about our progress in dialysis care?

PMID- 21905524
TI  - The role of APS in a nephrology practice.

PMID- 21905525
TI  - The ESA saga: a perfect storm of failed expectations and over-regulation.

PMID- 21905526
TI  - The possible effects of CMS's 'non-decision' on a national coverage decision for
      ESA therapy.

PMID- 21905527
TI  - Getting patients and renal staff to embrace 'fistula first/catheter last'.

PMID- 21905528
TI  - In-center self-care hemodialysis: an unappreciated modality in renal care.

PMID- 21905530
TI  - How to climb Capitol Hill and be an advocate.

PMID- 21905529
TI  - Self-care dialysis fits in with new economic challenges for providers.

PMID- 21905531
TI  - Heterotopic epithelial inclusions with micrometastatic mammary carcinoma in a
      sentinel lymph node.

PMID- 21905532
TI  - Intracranial hemorrhage from undetected aneurysmal rupture complicating
      transphenoidal pituitary adenoma resection.
AB  - We report a case of a 39-year-old man who presented with a nonfunctioning
      pituitary macroadenoma which extended into the suprasellar region. He underwent a
      transcranial resection of the tumor followed eight months later by
      transsphenoidal surgery for the residual tumor. Postoperatively he developed
      massive subarachnoid and intraventricular hemorrhage. A cerebral angiogram
      revealed a leaking anterior communicating artery aneurysm which was not seen on
      the computed tomography angiography and magnetic resonance angiography before the
      surgery. Complications of transsphenoidal surgery, particularly vascular
      hemorrhagic complications, and risk of rupture of undetected aneurysms are
      discussed.

PMID- 21905533
TI  - Paratesticular leiomyosarcoma: case report and review.
AB  - Paratesticular leiomyosarcoma is a rare entity. Greater than 95% of tumors
      arising within the scrotal sac are testicular in origin. Of the paratesticular
      tumors, rhabdomyosarcoma accounts for nearly half of malignant masses.
      Paratesticular leiomyosarcoma is infrequently encountered, resulting in a
      relative paucity of literature regarding this tumor type. Here we present a case
      report of a leiomyosarcoma arising from the spermatic cord in a 71-year-old man
      and review the literature regarding paratesticular leiomyosarcoma presentation,
      diagnosis and treatment.

PMID- 21905534
TI  - Refractory DKA as first presentation of acromegaly and a potential role for
      continuous venovenous hemofiltration in its successful management.
AB  - Diabetic ketoacidosis is rarely encountered in acromegaly. We present a unique
      patient with refractory diabetic ketoacidosis (DKA) as a first presentation of
      acromegaly. In addition to an insulin drip and intravenous fluids, our patient
      was managed with octreotide therapy. As he developed acute renal failure in the
      context of renal hypoperfusion, continuous venovenous hemofiltration (CVVH) was
      instituted. After only three days of therapy, the growth hormone (GH) level
      dropped circa fourfold and insulin growth factor 1 (IGF-1) level dropped
      ninefold. We postulate a hypothetical role of CVVH in removal of plasma GH and
      IGF-1, similar to the clearance of other medium size molecules such as brain
      natriuretic peptide and procalcitonin. If this is confirmed in future studies,
      CVVH may have therapeutic implications for the above category of patients.

PMID- 21905536
TI  - Emollient empathy.

PMID- 21905535
TI  - Farewell to a warrior.

PMID- 21905537
TI  - A journey into the past: history of the Connecticut State Medical Journal 1936
      1958. 1976.

PMID- 21905538
TI  - A half century of Connecticut Medicine. 1986.

PMID- 21905539
TI  - Will print journals last much longer?

PMID- 21905540
TI  - "Horse and buggy days".

PMID- 21905542
TI  - Simple answers.

PMID- 21905541
TI  - The data Gestapo.

PMID- 21905543
TI  - CDHC, a possible change agent promoting access to care.
AB  - Access to oral health care has been a topic of concern among dental and community
      health professionals in the United States for some time. The American Dental
      Association is piloting a new program aimed at expanding the current dental
      health workforce and alleviating some of the problems associated with access to
      care. This paper explores the potential benefits of the community dental health
      coordinator program while examining some of the lessons learned in its initial
      implementation in Oklahoma.

PMID- 21905544
TI  - Getting help for children: the need to expand the dental workforce.
AB  - Millions of children in America suffer from poor oral health due to lack of
      access to dental care. The landmark U.S. Surgeon General's Report in 2000
      highlighted significant disparities, yet poor oral health remains an epidemic.
      America's system of delivering dental care is poorly equipped to address access
      disparities. However, opportunities abound to improve access and expand the
      dental workforce. Creative thinking and innovative solutions are needed to expand
      care to children in need.

PMID- 21905545
TI  - Breaking down barriers to oral health for all Americans: the role of workforce.
AB  - This statement from the American Dental Association is the first in a series
      offering the ADA's vision of a healthier, more productive nation, enabled by
      breaking down the barriers that impede or entirely prevent millions of Americans
      from enjoying good oral health. It is included as part of this issue to
      articulate the ADA's perspective on the national access debate.

PMID- 21905546
TI  - Societal expectations and the profession's responsibility to reform the dental
      workforce to ensure access to care for children.
AB  - Societal expectations raise the issue of the nature of a profession and a
      profession's relationship with society. Influential policy leaders want reform of
      the oral health workforce and delivery system in such a manner as to ensure that
      improvements are made for accessing care, particularly for vulnerable and
      disadvantaged populations, especially children. This essay is based on a
      presentation to the House of Delegates of the California Dental Association on
      Nov.13, 2009.

PMID- 21905547
TI  - A view from both sides.
AB  - This letter to the editor is from one of the key figures in caries management by
      risk assessment. Dr. Featherstone brings a unique perspective to the access
      issue. He grew up in New Zealand and experienced care under the dental therapist
      provider model. His letter is included here because it complements the other
      articles by providing his views on CAMBRA in the context of addressing barriers
      to care.

PMID- 21905548
TI  - Can you hear me now?

PMID- 21905549
TI  - Defining ourselves as nurses.

PMID- 21905550
TI  - The public and self-image of holistic nurses: realizing our potential for
      changing our image.

PMID- 21905551
TI  - The IOM report: one more time with music?

PMID- 21905552
TI  - Nurse Jackie and nurse ethics: How TV and the media influence our public image.

PMID- 21905553
TI  - The image of nursing in Botswana.

PMID- 21905554
TI  - Members share: images of nursing.

PMID- 21905555
TI  - Professional coaching and holistic nursing are complementary.

PMID- 21905556
TI  - AHNA as a holistic workplace.

PMID- 21905557
TI  - Creating holistic workplaces wherever we go.

PMID- 21905558
TI  - Holistic nursing leadership: changing the workplace and the field.

PMID- 21905559
TI  - My holistic workplace: alpacas & therapy.

PMID- 21905561
TI  - My holistic workplace.

PMID- 21905560
TI  - Workplace cures: feng shui approach.

PMID- 21905562
TI  - Holistic philosophy changed my work.

PMID- 21905563
TI  - Defining the holistic workplace.

PMID- 21905564
TI  - Why feminism matters in maternity care.

PMID- 21905565
TI  - Expert witnesses: Jones v Kaney and the Law Commission's report.

PMID- 21905566
TI  - The baby, the bathwater and the bath itself: a response to Tyrer et al.'s review
      of the successes and failures of dangerous and severe personality disorder.
AB  - A recent paper by Tyrer et al. in this journal has reviewed the dangerous and
      severe personality disorder (DSPD) initiative in the assessment and management of
      severe personality disorder associated with high risk. This previous paper
      summarized the authors' perceptions of the successes and failures of the DSPD
      pilot. In the present paper we identify some inaccuracies in the previous review
      and provide a critique of the conclusions reached.

PMID- 21905567
TI  - Ethical and legal issues in organ transplantation: Indian scenario.
AB  - In 1994, the Government of India enacted the Transplantation of Human Organs Act
      (THOA) to prevent commercial dealings in human organs. However, a greater number
      of scandals involving medical practitioners and others in the kidney trade has
      surfaced periodically in every state in India. The present regulatory system has
      failed mainly due to the misuse of Section 9(3) of the THOA, which approves the
      consent given by a live unrelated donor for the removal of organs for the reason
      of affection or attachment towards the recipient or for any other special reason.
      Currently in India, approximately 3500-4000 kidney transplants and 150-200 liver
      transplants are performed annually. However, the availability of organs from
      brain-dead persons is very low. As a result, live related or unrelated donors
      form the main source of organ transplantation. Therefore, physicians and policy
      makers should re-examine the value of introducing regulated incentive-based organ
      donation to increase the supply of organs for transplantation and to end unlawful
      financial transaction.

PMID- 21905568
TI  - Psychiatric evidence in criminal courts: the need for better understanding.
AB  - The rules of admissibility of expert evidence from mental health professionals
      are not clear. The task of a psychiatrist providing expert opinion to criminal
      courts is far from clear. Psychiatric experts are trained in a particular set of
      ethical and philosophical frameworks. They have expertise in the diagnosis and
      management of behaviours arising from mental disorders. The concept of mental
      disorder itself is a dimensional one. Such a dimensional view of human behaviour
      and mental disorders is hard to fit into the categorical view of human behaviour
      that the law follows. The task of the psychiatric expert is to marry these two
      philosophically different branches. Such a task would be facilitated by clear
      rules of admissibility of expert psychiatric evidence, clear definition of the
      roles and limitations of psychiatric evidence in criminal cases, a better
      understanding and training of mental health professionals in legal principles and
      a better understanding by the legal professionals of the mental health concepts.
      This article aims to analyse the legal basis of the admissibility of expert
      mental health evidence, the differences in the philosophies of the two
      disciplines and the challenges in addressing legal criteria while staying
      faithful to the ethos of psychiatry and psychology.

PMID- 21905569
TI  - Homicide/suspicious death statistics for cases submitted to the forensic science
      laboratory in the Republic of Ireland for 2004-2008.
AB  - The purpose of this study was to examine the trends and patterns of homicide in
      the Republic of Ireland over a five-year period (2004-2008). In total, 293 cases
      are covered in the survey. The majority of the victims were men. The most common
      age group of victims was 20-29 years old. The majority of the suspects were also
      men. The most common age was also 20-29 years old. Stabbing was the most common
      method used to kill and this often featured multiple wounds to the head and body.
      Shooting and blunt force traumas were also common. Homicides are more likely to
      occur over the weekend period. This study also explored the relationship between
      the suspect and the victim, the motive and the location of the fatal assault. In
      the majority of cases, the victim and the perpetrator were known to each other.
      The site of the fatal assault was most likely to be a residence and the most
      frequent motive was an argument/quarrelling. A small number of cases involved
      multiple fatalities, often involving relatives. The figures were compared with
      other international studies; our findings are broadly in agreement with them.

PMID- 21905570
TI  - An RSU by any other name: thoughts on the naming of secure units.
AB  - Names are powerful symbols which contribute to internal and external perceptions
      of an individual or institution. This paper discusses the names given to Regional
      Secure Units established following the Butler Report, and discusses some of the
      reasons underlying the choice of name. Understanding the derivation of names can
      assist understanding of the development of forensic psychiatry as a separate
      specialty and awareness of its history.

PMID- 21905571
TI  - Could lactates in vitreous humour be used to estimate the time since death?
AB  - Vitreous humour (VH) is a useful medium for postmortem analysis. During the
      supravital period, anaerobic glycolysis that occurs results in the increased
      lactate concentration (L) in cytosol. We analysed the concentration of lactic
      acid in 567 samples of VH from 63 autopsy cases by a repetitive withdrawal of VH
      from the same corpse, while the outside temperature remained constant. The
      samples were taken from the same eye in intervals of three hours for the period
      of 24 hours. The subjects were divided into two groups: group 1 included
      individuals who died during winter and were kept for analysis at 40C, while group
      2 consisted of those who died during spring and autumn (continental climate) and
      were stored at 200C. Only the cases of a sudden traumatic death of previously
      healthy individuals were included in the study. Statistically significant
      correlation of L against postmortem interval (PMI) was observed in the group 1
      experiment (r = 0.675; P < 0.01), but the effect of hypothermia made the
      estimation of PMI practically impossible. A much stronger correlation of L
      against PMI was observed in group 2 (r = 0.866, P < 0.01); a functional
      relationship between PMI and L were demonstrated using the formula PMI = 1.696 x
      L - 10.562, which enabled more accurate prediction of the PMI.

PMID- 21905572
TI  - Frequent detection of stomach contents in accidental drowning.
AB  - We analysed forensic autopsies of 536 consecutive adults to determine the
      relationship between the presence of stomach contents and the manner of death.
      Stomach contents were identified in 27 (79.4%) of 34 accidental drownings and in
      22 (43.1%) of 51 suicidal drownings (P < 0.01). Accidental drowning was the
      manner of death most frequently associated with the presence of stomach contents,
      and stomach contents were found significantly more often in this type of death
      than in suicidal drowning. These findings indicate that food intake is a factor
      possibly related to accidental drowning and suggest that fasting may be required
      before swimming or taking a bath to prevent accidental drowning.

PMID- 21905573
TI  - 'A frightening experience': detainees' and carers' experiences of being detained
      under Section 136 of the Mental Health Act.
AB  - AIMS: This research reports on the views of detainees and their carers of their
      experiences of being detained under Section 136 (S136) of the Mental Health Act
      1983. Individual interviews were conducted with 18 detainees and six carers.
      METHOD: A semi-structured questionnaire was administered face-to-face to gather
      qualitative data, which was analysed using a grounded theory approach. RESULTS:
      The results indicated a general dissatisfaction with the quality of care and
      treatment from both police and professionals. Though several detainees recognized
      the need for police to be involved, most felt they lacked the skills needed to
      meet the needs of mentally ill people. Nearly all participants felt that the
      police station was an inappropriate setting for further assessment, and found
      their experiences in police cells distressing, making them feel like criminals.
      CONCLUSIONS: Detainees and carers would like to see the provision of a place of
      safety other than emergency departments or police stations, and this study
      reinforces the Mental Health Code of Practice 2008 which states that police
      stations should only be used on an exceptional basis.

PMID- 21905574
TI  - Can we assess the age of bruises? An attempt to develop an objective technique.
AB  - AIMS: The aims of this study were (A) to investigate whether the number of years
      of forensic experience affected the accuracy with which forensic experts (FEs)
      were able to age bruises and (B) to identify the properties and colours of a
      bruise that were utilized by FEs in their assessment of bruise age. The study
      then investigated the possibility of using a more objective technique. It was
      decided to use readily available digital photography and software to objectively
      assess changes in bruise colouration and to investigate if this can be used to
      age bruises. METHODS: Twenty-three FEs were shown 25 photographs of bruises of
      varying but known ages and asked to estimate the ages. In part two of the study,
      bruises were inflicted on volunteers using a vacuum pump and photographs taken of
      the bruise daily from infliction to resolution. The images were analysed using
      Adobe Photoshop. Red, green and blue (RGB) values were recorded for each bruise
      and analyses carried out comparing the values over time between subjects and
      within subjects. RESULTS: This study both enhanced and supported a previous
      conclusion that visual assessment of photographs is an unreliable method for
      ageing bruises. Additionally, it found that the degree of forensic experience had
      no effect on accuracy. It also identified that colour (particularly yellow, red
      and purple) and intensity of colour were the most commonly used properties of a
      bruise in the assessment of its age. The RGB method proved to be a reliable
      technique with which to measure bruise colour, but its validity in the assessment
      of bruise age was poor. CONCLUSIONS: Visual assessment of bruises is unreliable
      and the accuracy of ageing was not improved by the degree of forensic experience.
      The RGB method gave highly reproducible results, but did not accurately assess
      bruise age. However, results within subjects suggested that there may be
      individual variation in haemoglobin metabolism.

PMID- 21905575
TI  - Effect of seated restraint and body size on lung function.
AB  - BACKGROUND: Previous studies of death during law enforcement restraint have
      focused on lying restraint positions; this study extends this work to seated
      restraint positions. METHODS: Lung function in a standing control position was
      compared with lung function in seated positions using 40 volunteers. RESULTS: No
      significant reduction in lung function was detected in an upright seated
      position. When participants were leant forward while seated, significant
      reductions in lung function occurred. The application of restraint holds in the
      seated, leant forward position resulted in a non-significant further reduction in
      lung function. Reductions in lung function were greater in those participants
      with higher body mass index (BMI). CONCLUSIONS: Seated restraint positions with
      the person leant forward may increase the risk of harm or death during prolonged
      restraint. The risk will be further increased where the person exhibits higher
      BMI.

PMID- 21905576
TI  - An anomalous origin of left coronary artery and sudden death in a soccer player:
      a case report.
AB  - Coronary artery anomalies, after hypertrophic cardiomyopathy, are the second most
      common cause of exercise-related sudden cardiac deaths. These anomalies have been
      associated with myocardial ischaemia, arrhythmia and sudden death during
      exercise. Anomalous origin of the left coronary artery from the right sinus of
      Valsalva with anterior or posterior courses is not always thought to be a benign
      anomaly. A 22-year-old man died suddenly on a football field. At autopsy, there
      was an abnormal origin of the left coronary artery from the right sinus of
      Valsalva. The abnormal course of the artery between the aorta and pulmonary trunk
      had limited victim's functional capacity. The history, cause of death and patho
      physiology are discussed, and some preventive strategies suggested.

PMID- 21905577
TI  - Career research opportunities for the medical laboratory scientist.
AB  - Medical Laboratory Scientists (MLS) typically practice in hospital laboratories;
      however there are multiple alternatives in research. This article details the
      advantages of working in a variety of research laboratory settings. These include
      public institutions, federal laboratory workplaces, private facilities, and
      industry settings. A view of the different research laboratory settings such as
      public institutions, federal laboratory workplaces, private facilities, and
      industry settings will be provided. An assessment on how MLS professionals can
      prepare for a career in research is outlined and the report concludes with a
      brief summary of the various aspects of the research setting.

PMID- 21905578
TI  - Importance of clinical microbiologists for U.S. healthcare infrastructure.
AB  - Clinical microbiologists are highly skilled scientists within national hospitals
      and reference laboratories who diagnose patients with infections by emerging
      pathogens. Most advanced training for clinical microbiologists occurs at
      universities, where an individual can receive certification as a "Medical
      Laboratory Scientist" (MLS). Unfortunately, many MLS programs have closed in the
      United States and this has caused a shortage of clinical microbiologists at U.S.
      hospitals and reference laboratories. This paper explores the present crisis in
      MLS training and its ramifications for the emergence of antibiotic-resistant
      bacteria, the economics of hospitals, and the overall health of the nation, and
      provides resolutions for better public health policy with respect to MLS
      education.

PMID- 21905579
TI  - Atypical cytogenetics in therapy-related myelodysplastic syndrome secondary to
      indolent B-cell lymphoma.
AB  - A case of therapy-related myelodysplastic syndrome (t-MDS) with unusual
      cytogenetics is presented. While therapy related myeloid neoplasms account for 10
      20% of all myeloid neoplasms, 90% of therapy related myelodysplastic syndromes
      (MDS) present with a del(7q) or a del(5q) and fewer than 1% present with a
      del(20q). In this case, the common cytogenetic pattern of either del(7q) or
      del(5q) is absent while presenting with an abnormal del(20q). Also demonstrated
      is the potently poor prognostic indicator of cytomegalovirus (CMV)
      seropositivity, even when seropositivity is matched between donor and recipient
      of hematopoietic stem-cell transplant. The patient also continues to demonstrate
      the inherent dangers of a stem-cell transplant, presenting with graft-versus-host
      disease (GvHD) while being a haploidentical 10 out of 10 HLA match to the
      allogeneic stem cell donor.

PMID- 21905580
TI  - Shigellosis with resultant septic shock and renal failure.
AB  - Septic shock is a rare, potentially life-threatening complication of bacterial
      dysentery. The clinical presentation of septic shock includes hypotension,
      bleeding, hypoxia, acidosis, and jaundice. Historically gram-negative organisms
      were the most frequent cause of nosocomial bloodstream infections. However
      isolation of gram-positive organisms has become increasingly frequent with
      Staphylococcus species accounting for over one half of all nosocomial bloodstream
      pathogens. Bacterial dysentery is an acute diarrheal illness characterized by
      abdominal cramping, fever, and the production of mucoid, bloody stools.
      Laboratory findings include positive stool culture and increased leukocytes in
      direct fecal exam. Chemistry and hematology values may be abnormal. The disease
      is usually self-limiting but administration of antibiotics and rehydration
      therapy may be warranted in severe cases. This case study describes a 53 year old
      male who presented with diarrhea and diabetic acidosis and subsequently developed
      respiratory distress and renal failure due to shigellosis. Discussion of disease
      pathogenesis and treatment are provided.

PMID- 21905581
TI  - Variation in pipetting may lead to the decreased detection of antibodies in
      manual gel testing.
AB  - BACKGROUND: Variation in pipetting technique can contribute to the failed
      detection of weakly reactive antibodies. This study evaluated the impact of
      pipetting technique on the sensitivity of antibody detection using the manual gel
      test. STUDY DESIGN AND METHODS: A total of 115 plasma antibodies were evaluated
      using the manual gel test (Ortho ID-MTS, Raritan, NJ). All antibodies were
      diluted to obtain 1+, w+, and undetectable reactions. Testing was performed in
      parallel using two pipetting techniques: cells and plasma pipetted into the gel
      card to allow an air gap and without an air gap. RESULTS: When cells and plasma
      were pipetted into the gel card without air gap, 12.4% of 1+ reactions (p <
      0.001) and 81.0% of w+ reactions (p < 0.001) were not detected. Overall, 24.7% of
      clinically significant (p < 0.001) and 29.7% of nonspecific antibodies (p < 0.05)
      became nonreactive. Antibody screening tests failed to detect 26.0% of passively
      acquired anti-D (p < 0.001), 38.0% of anti-E (p < 0.001), 28.0% of anti-Jk(a) (p
      < 0.001), 20.0% of anti-K (p < 0.05), and 35.0% of warm auto antibodies (p <
      0.05). CONCLUSION: Cells and plasma pipetted manually without leaving an air gap
      in the gel card failed to detect clinically significant antibodies. An optimal
      pipetting technique is recommended to ensure the detection of weakly reactive
      antibodies.

PMID- 21905582
TI  - Perceived emotional aptitude of clinical laboratory sciences students compared to
      students in other healthcare profession majors.
AB  - Emotional aptitude can be defined as the ability to recognize and manage one's
      own emotions and interpret the emotions of others. It has been speculated that
      Clinical Laboratory Sciences students may lack the emotional skills to most
      effectively interact with patients and other healthcare professionals, therefore
      a logical hypothesis would be that they would evaluate their own emotional
      intelligence lower than students from other healthcare majors. While this has
      been a topic of discussion in healthcare, a lack of research has been conducted
      to validate this assumption. This study assesses the perceived emotional aptitude
      of Clinical Laboratory Sciences students compared to students of other healthcare
      majors in the Dumke College of Health Professions at Weber State University. The
      perceived emotional aptitude of the healthcare students was determined by
      completion of a self-evaluation questionnaire that included questions about one's
      emotions, their understanding of others' emotions, and how they manage conflict.
      A total of 401 questionnaires were completed, compiled, and analyzed. Although
      minor differences were seen in the responses, statistical analysis found these
      differences to be insignificant. The perceived emotional aptitude of Clinical
      Laboratory Sciences students was insignificantly different than that of students
      of other healthcare majors at the Dumke College of Health Professions.

PMID- 21905583
TI  - Estimation of serum hyaluronidase activity overcoming the turbidity interference.
AB  - The assay of mammalian hyaluronidases (HAases) is important in understanding the
      role of the hyaluronan-hyaluronidase (HA-HAase) system in various
      pathophysiological processes. Despite several quantitative assay method options,
      the Morgan-Elson colorimetric method modified by Reissig et al is considered the
      best for determining the activity in clinical samples. However, the sensitivity
      of the method was greatly limited by presence of protein above 400 microg due to
      turbidity interference that led to chromogen quenching. Therefore, an effort has
      been made to reinvestigate the Reissig et al method. In the reinvestigated
      method, a standardized optimal 0.32 M potassium tetraborate (PTB) was used
      against 0.13 M (native) to overcome the turbidity interference. The estimated
      mean OD at 585 nm of serum for native method was 0.043 (95% CI: 0.040 to 0.045),
      while that for the re-investigated method was 0.138 (95% CI: 0.133 to 0.143, p <
      0.0001). The mean OD at 585 nm of serum of native method was significantly lower
      than that of re-investigated method (p < 0.05) at all protein levels. This was
      also true for estimated mean OD at 585 nm of plasma. The mean intrasample CVs for
      native and re-investigated methods were 0.9% and 0.5%, respectively, for normal
      serum. Furthermore, the repeatability coefficient of normal serum for native was
      0.003 IU, while re-investigated method experienced that of 0.002 IU.

PMID- 21905584
TI  - Myeloproliferative neoplasms: an overview.

PMID- 21905585
TI  - Myeloproliferative neoplasms: the role of molecular markers.

PMID- 21905586
TI  - Essential thrombocythemia.

PMID- 21905587
TI  - [Risk stratification and prediction of operative treatment outcome in
      cardiosurgery].

PMID- 21905588
TI  - Patency of internal thoracic artery and vein grafts according to revascularized
      coronary artery properties.
AB  - Long-term results of surgical myocardial revascularization are determined by the
      quality of grafts and the progression of atherosclerosis in coronary arteries.
      The aim of the study was to evaluate the patency rate of internal thoracic artery
      and great saphenous vein grafts in relation to the hemodynamic properties of
      revascularized coronary artery. The patency of internal thoracic artery and great
      saphenous vein grafts was analyzed in relation to the degree of coronary stenosis
      estimated by angiography and the diameter of distal portion of coronary artery
      assessed intra-operatively. The long-term patency of great saphenous grafts
      depends on the distal coronary artery diameter but not on the degree of coronary
      artery stenosis. The patency of internal thoracic artery graft depends on the
      degree of coronary artery stenosis but not on the distal coronary artery
      diameter. The internal thoracic artery is the superior graft in coronary surgery,
      but the low patency rate in case of moderate coronary artery stenosis emphasizes
      the importance of selective approach.

PMID- 21905589
TI  - [Quantitative analysis of vascular network of oculogyric nerve nuclei].
AB  - INTRODUCTION: Nuclei of oculogyric nerves (principal oculomotor nucleus,
      trochlear nucleus and abducens nucleus) are densely vascularized brainstem
      structures. The aim of this study was to determine quantitative characteristics
      of the vascular network of these nuclei. MATERIAL AND METHODS: The study was done
      on 30 adult brainstems, both male and female, without diagnosed neurological
      disturbances. Three-millimetre-thick stratums were taken in transversal plane and
      cut in 0.3 micrometer semi-serial sections stained with Mallory method. The
      images of studied nuclei were taken with "Leica" DM 1000 microscope and "Leica"
      EC3 digital camera under 400x magnification, and analyzed by ImageJ software with
      A 100 grid. The statistical analysis was performed by Statistical Package for the
      Social Sciences software with 5% level of significance. RESULTS: A statistically
      significant difference was found in the volume and surface density between
      principal oculomotor nucleus and trochlear nucleus, and between trochlear nucleus
      and abducens nucleus. No difference was found in the length density. DISCUSSION:
      The results of this research match the results of studies on characteristics of
      vascular network of oculogyric nerve nuclei, while the comparison of vascular
      networks of these nuclei, substantia nigra, vestibulocochlear nuclei and
      precentral gyrus illustrates differences in quantitative characteristics of blood
      vessels in these structures. CONCLUSION: Blood vessels of principal oculomotor
      nucleus and abducens nucleus have similar dimensions and approximately the same
      arborization pattern, while vessels of trochlear nucleus have significantly
      smaller dimensions and density.

PMID- 21905590
TI  - [The most frequent injury with mechanical corn picker during harvest--possibility
      of prevention].
AB  - INTRODUCTION: Inappropriate machine operating, long work hours and decreased
      concentration of machine operators create conditions for getting injured A corn
      picker is the most often cause of hand injuries among agricultural machineries.
      MATERIAL AND METHODS: The study included 43 persons with hand injuries during
      corn harvest, treated in the four-year period (2006-2009). The study subjects
      were analysed by sex, age, season, type of injury, affected parts of the hands,
      length of treatment and data on being trained to work with the corn picker.
      RESULTS: In the observed period hand injuries caused by a corn picker occurred
      10.75 times a year on average on the territory gravitating to the Clinical Centre
      of Vojvodina. The most frequent hand injuries were recorded in male operators,
      most of them aged 21-59, and the greatest number of injuries happened in October.
      According to the type, crushing of hand was the dominant type of injury. Fingers
      of hand were most frequently grabbed The average duration of treatment was 14.37
      days, and the majority of patients were treated in hospital up to 14 days.
      DISCUSSION AND CONCLUSION: The average occurrence of hand injuries reported in
      this paper is significantly lower than it was reported in one study conducted
      earlier. The data regarding training to operate the respective machinery indicate
      that 93.2% of the injured have not been trained appropriately, and 37.12% did not
      have any personal protective devices. Training of farmers to operate agricultural
      machinery should be carried out continually in future, as it has been regulated
      by the Law on Safety at Work and Health.

PMID- 21905591
TI  - Vascular dementia: clinical and neuroradiological correlation.
AB  - All stroke patients admitted to Banjaluka Clinical Centre during one year were
      evaluated by the standard protocol during the hospitalization and three months
      after the stroke. It included clinical, functional and neuropsychological
      examination and neuroimaging. Dementia was diagnosed according to the criteria of
      National Institute of Neurological Disorders and Stroke-Association
      Internationale pour la Recherche et l'Enseignement en Neurosciences. Demographic
      and clinical variables were examined. After the exclusion of the patients who
      died (n = 139) and those who refused to be interviewed during the 3-month follow
      up (n = 52) and those with pre-stroke dementia (n = 22), a total of 273 (58.8%)
      patients underwent neuropsychological examination 3 months after the stroke.
      Forty-nine (19.52%) of them met the criteria for vascular dementia. The
      predictors of vascular dementia were age, atrial fibrillation, cognitive and
      functional impairment on admission and functional outcome, subcortical lacunar
      infarctions, leukoaraiosis, multiple and bilateral brain lesions. Dementia is
      frequent after stroke and it cannot be determined by a single factor. A
      combination of several factors increases the critical threshold for cognitive
      decline.

PMID- 21905592
TI  - [Influence of different types of surgical suture materials on mechanical damage
      of oral mucosa].
AB  - INTRODUCTION: Throughout history many kinds of different suture materials have
      been used for closing and suturing surgical wounds. Medical literature describes
      four basic characteristics of suture material: knot safety, tensile strength,
      tissue reaction and wound safety. The tissue reaction is reflected in an
      inflammatory response, which, though minimal, occurs during first two to seven
      days after implanting suture into the tissue. The aim of this research was to
      investigate whether different suture materials affect the development of
      decubital damage of oral mucosa, which to a great extent can compromise the
      process of wound healing. MATERIAL AND METHODS The investigation was designed as
      a prospective clinical study including 150 patients of both genders, aged between
      25 and 60. The patients were distributed into three groups of 50 persons. The
      suture Black Silk was used in the first group, designated as a control group.
      Nylon and Vicril were used in the second and third group, i.e. experimental
      groups, respectively. Decubital damage of the surrounding soft tissues was the
      main parameter for monitoring the effects of selected suture materials on the
      oral mucosa. CONCLUSION: The comparison of results obtained for the investigated
      suture materials after suturing oral mucosa revealed that certain advantage could
      be given to synthetic monofilament suture materials.

PMID- 21905593
TI  - [Stress as a risk factor in the development of brain stroke].
AB  - INTRODUCTION: In many developing countries and in countries in transition, an
      increased incidence of cerebrovascular disease has been observed. The aim of this
      study was to determine the influence of acute and chronic stress on the
      development of acute brain stroke and its relapse. MATERIAL AND METHODS: The
      study included all recorded cases of cerebrovascular disease in the municipality
      of Doljevac in the period 2005-2007 (the stroke victims), and 230 healthy
      controls. By using the method of interview, the frequency of chronic stress
      situations was examined, as well as the occurrence of acute stress situations 24
      hours prior to the acute brain stroke and its relapse. RESULTS: In the group
      which consisted of stroke victims, a large number of subjects was found to have
      had an acute stress 24 hours prior to the onset of the disease, and the type of
      stress which proved to be statistically significant was the one which had been
      provoked by problems between family members (Chi2 = 4,03: p = 0,04). All of the
      chronic stressors were more frequent in the group consisting of stroke victims
      than in the control group and among the statistically significant stressors were
      stressful situations in the family and at work. In recidivists, a greater
      presence of acute and chronic stressors was observed, but the statistical
      significance was not proved when this disease occurred again. CONCLUSION: The
      presence of acute stressors was found to have been more frequent in the group of
      stroke victims 24 hours prior to the onset of the disease. The effect of acute
      and chronic stressors upon the brain stroke recidivism has not been statistically
      proved yet.

PMID- 21905594
TI  - [Predictors of self-rated health of citizens on the territory of endangered
      political security].
AB  - INTRODUCTION: Self-rated health is generally accepted by researchers as a valid
      measure of health status. The aims of the study were to investigate how the adult
      inhabitants of northern Kosovska Mitrovica described their health and which
      variables were the predictors of self-rated health status among that population.
      METHOD: The research was done as a cross-sectional study on the representative
      sample of 318 adult inhabitants of northern Kosovska Mitrovica in 2006. The
      instrument of research was a questionnaire containing questions about self-rated
      health and demographic and socio-economic characteristics, mental health, social
      interaction, possibilities of performing everyday activities, health behaviour
      and habits, diseases and injuries, utilization of health care service. The
      independent variables were defined through the factor analysis taken from these
      groups of questions. The multivariate stepwise linear regression was done to
      determine the correlation between self-rated health and independent variables.
      RESULTS: More than half of the respondents (54.7%) assessed their health as good
      or very good. The predictors of self-rated health were gender, mood problems,
      myocardial infarction, chronic bronchitis, psychic and neurotic disorders,
      rheumatic arthritis, high blood sugar, utilization of private gynaecologist
      service and paying for diagnostic service. CONCLUSION: Most of the respondents
      from northern Kosovska Mitrovica assessed their own health as good or very good.
      Bad and very bad health was significantly associated with females, problems with
      mood, myocardial infarction, chronic bronchitis, psychic or neurotic disorders,
      rheumatoid arthritis and high blood sugar. Good and very good health was
      significantly associated with utilization of private gynaecologist service and
      paying for diagnostic service.

PMID- 21905595
TI  - Postoperative influence of interferon alpha on patients with renal cell
      carcinoma.
AB  - The aim of this study was to show whether immunotherapy should be administered in
      patients with renal cell carcinoma after radical nephrectomy in N0 and N1 stage
      of disease. The research was conducted in 60 patients with renal adenocarcinoma
      after radical nephrectomy. The study group included two subgroups of patients:
      the treatment group consisted of 30 patients receiving immunotherapy, of whom 15
      had N1 disease stage and 15 had N0 disease stage; and the observation group
      consisted of 30 patients who did not receive immunotherapy, of whom 15 had N1
      disease stage and 15 had N0 disease stage. It was shown that the administration
      of immunotherapy in N0 stage neither improved the overall survival nor postponed
      the appearance of metastases and that immunotherapy in N1 stage even worsened the
      prognosis in overall survival as compared with the observation group. There is no
      benefit of administering immunotherapy in patients with N0 and N1 stage of
      disease after radical nephrectomy.

PMID- 21905596
TI  - [Treatment effects of co-amoxiclav (Amoxiclav 2x) in acute exacerbation of severe
      chronic obstructive pulmonary disease: clinical evaluation].
AB  - INTRODUCTION: The exacerbation of chronic obstructive pulmonary disease is most
      often induced by an infection of bacterial origin in over 50% of the cases (or
      mixed bacterial and viral infection). This study was aimed at evaluating clinical
      effects of antibiotics co-amoxiclav. Amoxiicillin with clavulanic acid in the
      treatment of patients with severe chronic obstructive pulmonary disease
      exacerbation. MATERIAL AND METHODS: The investigation included 38 patients with
      severe chronic obstructive pulmonary disease exacerbation hospitalized at the
      Institute for Pulmonary Diseases of Vojvodina, Sremska Kamenica. The patients
      were randomly selected for the antibiotic treatment with Amoxiclav twice a day in
      12 hour intervals. The clinical effects of the applied treatment were evaluated
      by analyzing certain laboratory findings, microbiological sputum findings and
      improvement of subjective symptoms. RESULTS: Of the examined subjects, 65% were
      males and 35% were females, their mean age being 66.4 +/- 8.86, and who were
      mostly smokers (73%). After the completion Of Applied antibiotic treatment, a
      significant reduction and normalization of all inflammation markers were
      recorded, as well as a significant improvement of the patients' subjective
      symptoms. The positive microbiological sputum findings (Haemophilus influenzae,
      Pseudomonas aeruginosa and Streptococcus pneumoniae) were recorded in 13.58% of
      the patients. The bacterial agent was eradicated on the third day of the applied
      treatment. The mean length of the treatment was 7.07 +/- 0.91 days, with no
      undesirable treatment side effects observed CONCLUSION The antibiotic therapy is
      justifiable as the initial treatment regimen of severe chronic obstructive
      pulmonary disease exacerbation and amoxicillin with clavulanic acid is reported
      as the first-line antibiotic drug in most pharmacotherapy guidelines.

PMID- 21905597
TI  - [Autoimmune thyroid disease and other non-endocrine autoimmune diseases].
AB  - INTRODUCTION: Autoimmune diseases are chronic conditions initiated by the loss of
      immunological tolerance to self-antigens. They constitute heterogeneous group of
      disorders, in which multiple alterations in the immune system result in a
      spectrum of syndromes that either target specific organs or affect the body
      systematically. Recent epidemiological studies have shown a possible shift of one
      autoimmune disease to another or the fact that more than one autoimmune disease
      may coexist in a single patient or in the same family. Numerous autoimmune
      diseases have been shown to coexist frequently with thyroid autoimmune diseases.
      AUTOIMMNUNE THYROID DISEASE AND OTHER ORGAN SPECIFIC NON-ENDOCRINE AUTOIMMUNE
      DISEASES: This part of the study reviews the prevalence of autoimmune thyroid
      disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune
      liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and
      several recommendations for screening have been given. AUTOIMMUNE THYROID DISEASE
      AND OTHER ORGAN NON-SPECIFIC NON-ENDOCRINE AUTOIMMUNE DISEASES: Special attention
      is given to the correlation between autoimmune thyroid disease and rheumatoid
      arthritis, systemic lupus erythematosus, syndrome Sjogren, systemic sclerosis and
      mixed connective tissue disease. CONCLUSIONS: Screening for autoimmune thyroid
      diseases should be recommended in everyday clinical practice, in patients with
      primary organ-specific or organ non-specific autoimmune disease. Otherwise, in
      patients with primary thyroid autoimmune disease, there is no good reason of
      seeking for all other autoimmune diseases, although these patients have a greater
      risk of developing other autoimmune disease. Economic aspects of medicine require
      further analyzing of these data, from cost/benefit point of view to justified
      either mandatory screening or medical practitioner judgment.

PMID- 21905598
TI  - [Gestational trophoblastic disease--literature review].
AB  - Gestational trophoblastic disease is characterized by abnormal proliferation of
      pregnancy-associated trophoblastic tissue with malignant potential. Gestational
      trophoblastic disease covers a spectrum of conditions including hydatidiform
      mole, invasive mole, choriocarcinoma and placental site trophoblastic tumour. It
      is very important to understand the pathophysiology and natural history of the
      disease in order to achieve faster recognition and effective treatment. The
      presence and course of the disease can be monitored with quantitative levels of
      human chorionic gonadotrophin in all cases. Clinical signs and symptoms are
      usually insufficient to diagnose and predict the extent of disease. Nowadays,
      gestational trophoblastic diseases are the best treated gynaecological malignancy
      thanks to modern technology. This review covers various aspects of gestational
      trophoblastic disease: its development, epidemiology, aetiology and pathogenesis,
      as well as its classification, clinical manifestations and diagnostic methods.

PMID- 21905599
TI  - [Pericarditis and cardiac tamponade: urgent condition not only in cardiology].
AB  - INTRODUCTION: Pericarditis is a condition with inflammation of the pericardium;
      however, most of these conditions are not infective and many of them are not even
      inflammatory. Pericarditis by its development can be acute, sub-acute and
      chronic, and later, recurring or relapsing. Apart from idiopathic, the causes of
      pericarditis are numerous, very often inflammatory, most frequently caused by
      viruses, or tumours and neoplasms, diseases of connective tissue, vasculitis,
      different allergic reactions, radiation, thyroid gland diseases, uraemia,
      dissection of aorta etc. CLINICAL PICTURE: Accumulation of fluid in the
      pericardium in the amount sufficient to cause significant obstruction of blood
      inflow in chambers can cause cardiac tamponade. If it is not treated immediately,
      the outcome may be fatal. The most common causes are tumours, viruses or uraemia.
      Cardiac tamponade should be suspected in patients with a decrease in systemic
      arterial pressure or presence of hypotension, tachycardia, silent and discreet
      heart beats, increase in systemic venous pressure (Beck triad). Electrocardiogram
      may result in tachycardia, QRS complex is of smaller voltage, often of reversed
      polarity. The amount of effusion is estimated by echocardiography CONCLUSION: The
      cause of pericarditis should always be searched for. On the other hand, during
      monitoring or treatment of numerous conditions which could be a frequent cause of
      pericarditis, the presence of pericardial effusion or cardiac tamponade should be
      suspected and detected in due time. A timely intervention--pericardiocentesis,
      can prevent the fatal outcome. Besides non-steroid anti-inflammatory medication,
      many prospective randomised studies propose colchicine as addition to the
      standard therapy. When opting for the proper treatment for pericarditis always
      keep in mind the current diagnosis and cause of this condition.

PMID- 21905600
TI  - [Factors predisposing to cervical artery dissection].
AB  - INTRODUCTION: Cervical artery dissection is a major cause of cerebral ischemia in
      young adults and can lead to various clinical symptoms, some of which are benign
      (e.g. headache, neck pain, Horner's syndrome, and cranial nerve palsy). However,
      most patients have a stroke or transient ischemic attack. EPIDEMIOLOGY: The
      incidence of cervical artery dissection is low and is estimated to be around 2.6
      per 100,000 inhabitants. Mortality and short-term recurrence rates are low:
      however; they may have been underestimated. PATHOPHYSIOLOGY: Although the
      pathophysiology is still unclear constitutional and partly genetic susceptibility
      of the arterial wall has been proposed as a causal factor; triggered by infection
      or minor trauma. PREDISPOSING FACTORS: In addition to the trauma to the neck,
      other risk fractors have been suggested, such as infection, migraine,
      hyperhomocisteinamia, and the 67TT genotype of the 5,10-methylene
      tetrahydrofolate reductase gene although evidence is sparse. GENETIC FACTORS:
      Cervical artery dissection is now considered a multifactorial disease caused by
      several genetic abnormalities and environmental factors acting synergistically.
      CONCLUSION: Research aimed at improving our understanding of the environmental
      and genetic factors predisposing to cervical artery dissection and assessment of
      long-term outcomes of this disease is needed. Better understanding of the
      underlying pathophysiology and the natural history of the disease through large
      prospective multicentre cohorts could also be helpful to improve therapeutic and
      preventive strategies. Several mutlticentre efforts are already under way to meet
      these needs.

PMID- 21905601
TI  - [Climate variations--risk factor of commiting suicide].
AB  - INTRODUCTION: Recently there have been more and more attempts at getting into
      connection the frequency of suicide with climate factors, humidity changes,
      atmospheric pressure. A large number of authors agree that suicide has
      meteorological character and that weather can be a provoking factor in suicidal
      persons. Suicides happen most frequently when the weather is warm, stable, and
      sunny; then, when it is rainy, cloudy and with high humidity, and least
      frequently when the atmospheric pressure and temperature are decreased
      accompanied with wind. CLIMATE VARIATIONS AND SUICIDE: Men who commit suicide
      show a significant, positive connection with indicators of temperature and
      exposure to sun, and a significant, negative connection with indicators of
      humidity and rainfall. Women who commit suicide show a less significant
      connection with climate variations--indicators. VIOLENT AND NON-VIOLENT SUICIDE:
      Regarding violent and nonviolent suicide, it has been proved that violent suicide
      is affected by environmental temperature, sunny intervals, raise in temperature
      in the previous few weeks. Higher environmental temperature and increase in air
      temperature in the previous few weeks are the most significant climate factors
      influencing the violent suicide rate. In addition, each degree exceeding 18
      degrees C increases the violent suicide rate by 3.8-5%. CONCLUSION: The result of
      many investigations of the influence of climate factors on committing suicide is
      that the suicide incidence reaches its peak during early summer. Also, the sun
      radiation the day before suicidal event is significantlly connected with the
      increased suicidal risk. There is a difference between sexes. If the sun were a
      trigger, men would have to be exposed to it for a longer time than women.

PMID- 21905602
TI  - [Therapeutic approach to actinomycosis--experience gained at the department of
      infectious and tropical diseases].
AB  - INTRODUCTION: Actinomycosis is a chronic infectious disease caused by anaerobic,
      gram-positive microorganisms from the order of Actinomyce or Propionobacterium.
      The disease manifests iself mostly in cervicofacial form and less frequently in
      thoracic and abdominal form. The study was aimed at reviewing clinical
      manifestations and therapeutic approaches in treatment of patients with
      Actinomycosis. MATERIAL AND METHODS: The study sample consisted of four patients
      with different clinical manifestations of Actinomycosis, who had been treated at
      the Institute for Infectious and Tropical Diseases in Belgrade in 2002, 2003,
      2006 and 2008. RESULTS: Four patients with Actinomycosis were treated during the
      above mentioned periods of time. One patient had kidney Actinomycosis, which
      developed into generalized Actinomycosis. Two patients had the most common
      cervical form, while the forth one had abdominal form; all patients received
      Penicillin G followed by Ampicillin, during the period of four weeks to up to a
      year. CONCLUSION: Actinomycosis is a rare disease, which imposes great diagnostic
      dilemmas. The treatment of this disease requires long term use of antibiotics.

PMID- 21905603
TI  - Diode laser trabeculoplasty in open angle glaucoma: 50 micron vs. 100 micron spot
      size.
AB  - The study was aimed at evaluating the efficacy of diode laser trabeculoplsaty in
      lowering intraocular pressure in patients with both primary open-angle glaucoma
      and exfoliation glaucoma by using different size of laser spot. This six-month,
      unmasked, controlled, prospective study included sixty-two patients with the same
      number of eyes, who were divided into two groups. Trabeculoplasty was performed
      with 50 micron and 100 micron laser spot size in the group I and group II,
      respectively. Other laser parameters were the same for both groups: the wave
      length of 532 nm, 0.1 second single emission with the power of 600-1200 mW was
      applied on the 180 degrees of the trabeculum. The mean intraocular pressure
      decrease in the 50 micron group (group 1) on day 7 was 24% from the baseline and
      after six-month follow-up period the intraocular pressure decrease was 29.8% (p <
      0.001). In the 100 micron group (group II), the mean intraocular pressure
      decrease on day 7 was 26.5% and after six months it was 39% (p < 0.001).

PMID- 21905604
TI  - An unusual origin of proximal coronary bypass anastomosis in a patient with
      porcelain aorta: how we solved the problem.
AB  - Severe calcification of the ascending aorta (porcelain aorta) is a very difficult
      condition in cardiac surgery because of a high embolization potential during the
      process of cannulation, aortic cross-clamping and a particular difficulty to
      suture the proximal anastomosis. We described a case of a 68-year-old female
      referred to our Institute due to unstable angina. Further diagnostics revealed a
      severe high grade, multilevel fibrolipid symptomatic carotid stenosis and ostial
      left main coronary artery stenosis and a highly calcified ascending aorta and
      aortic arch. We performed simultaneous carotid segment replacement with the
      Dacron prosthesis and revascularisation of the left anterior descending coronary
      artery. Proximal venous anastomosis was created in the Dacron prosthesis of the
      right carotid artery. Perfusion of the patient was achieved via the graft sutured
      at the right subclavian artery due to impossibility of direct aortic cannulation.

PMID- 21905605
TI  - [Multifocal choroidopathy syndrome--a case report].
AB  - INTRODUCTION: Multifocal choroidopathy syndromes are a group of rare disorders,
      which involve a primary pathologic process occurring at or near the level of the
      retinal pigment epithelium, with or without choriocapillaris involvement. The
      aetiology of multifocal choroidopathy syndrome is still unknown. A CASE REPORT:
      We present a case of multifocal choroidopathy syndrome. A 54-year-old woman was
      referred to our department with blurred vision on both eyes, mild ocular pain,
      accompanied by metamorphopsia, floaters, scotomas and photopsia. The anterior
      segment examination showed small to medium size keratic precipitates, posterior
      synechiae, and iris atrophy. Mild to moderate aqueous inflammation with cells and
      flair was present in the anterior chamber. The fundus examination showed multiple
      small yellow--white spots, round-shaped changes located at the level of the
      retinal pigment epithelium and choriocapillaris. According to the fluorescein
      angiography the active lesions exhibited blockage of the early choroidal
      fluorescence followed by late staining The old inactive lesions corresponded to
      the retinal pigment epithelium windows defects. The laboratory examination showed
      high level of blood glucose, C reactive protein, cholesterol HDL, LDL,
      triglycerides. According to the immunological examination the C3 component of
      complement was lower (0.630), as well as the C4 component of complement (0.158),
      and the immunological complex in blood was elevated (171). ELIZA test on viral
      infection showed Citomegalo viruses IgG positive, Herpes Simpler Virus lgG
      positive, Varichela Zoster Virus lgG positive. The results of human leucocyte
      antigen typization were humuan leucocyte antigen A1:A2, human leucocyte antigen
      A2:A24(9), human leucocyte antigen B1:B44(12), human leucocyte antigen
      B2:B60(40), human leucocte antigen C1:Cw3, human leucocyte antigen C2:Cw5. The
      radiological examination of lungs, the Mantoux test, Treponemnal serology,
      Toxocara and Toxoplasma serology, magnetic resonance of endocranium and orbit
      were also performed. The multiple viral infection, which was detected in our
      patient with immunological abnormalities pointed to an underlying autoimmune
      mechanisnm, possibly triggered by an infectious agent, a virus.

PMID- 21905606
TI  - [Ischaemic stroke in children: diagnostic and therapeutic specificity].
AB  - INTRODUCTION: Although more common in older adults, stroke occurs in neonates,
      infants and children as well, resulting in significant morbidity and mortality.
      EPIDEMIOLOGY: The incidence of childhood ischemic stroke exceeds 3.3 in 100,000
      children per year. Stroke is one of the top ten causes of death in children. RISK
      FACTORS: Children's strokes are often caused by birth defects, injections (e.g.
      meningitis, encephalitis), trauma, and blood disorders. Risk factors for stroke
      are recognized in more than 75% of children. The most common cause of stroke in
      children is probably congenital or acquired heart disease. CLINICAL PRESENTATION:
      Children often experience different symptoms of stroke to adults. These can
      include seizures, headache and fever. However, many of" the symptoms of stroke in
      children are similar to those experienced by adults (paralysis, speech and visual
      impairment). DIAGNOSTIC EVALUATIONS: Urgent neuroimaging is important for
      confirming the diagnosis of stroke. It is necessary for clinicians to conduct a
      thorough investigation for possible cardiac, vascular, and hematologic risk
      factors in all patients. THERAPY: The appropriate choices for in-hospital acute
      treatment and secondary preventative strategies, including aspirin and
      anticoagulants, are controversial. The recommendations for children are based
      mainly upon extrapolation from studies involving adults, and the clinical
      experience of experts, as reflected in consensus guidelines. CONCLUSION: Advanced
      forms of thrombolytic and neuroprotective agents may become more readily
      available to paediatric stroke patients when both the general public and medical
      staff become more aware of this disorder.

PMID- 21905607
TI  - [Marie Curie, nee Maria Sklodowska (1867-1934)--contribution to the development
      of radiology].
AB  - Marie Curie, nee Maria Sklodowska, was born on November 7, 1867 in Warsaw
      (Poland). She suffered from leukaemia and died on June 4, 1934. She was buried
      with full honours at Pantheon. Marie Curie and her husband Pierre Curie
      discovered the radioactive elements Polonium (84Po210), Thorium (90Th232) and
      Radium (88Ra226). Marie Curie introduced the term radioactivity into science. She
      was the first woman who got Ph.D. in France, the first woman professor at
      Sorbonne, Paris and Medical Academy. Of all the women who have ever won the Nobel
      Prize, Marie Curie was the only who received it twice. During World War I Marie
      Curie designed a mobile x-ray room "radiologic car". Marie Curie had an x-ray
      machine installed into a car and demonstrated how to use its dynamo for electric
      power production necessary for the x-ray machine to work. She had 20 cars with
      moving radiological lab made and trained 150 people to work on them. She brought
      something radically new into military medicine--mobile x-ray diagnostics. With
      the discovery of radioactive elements a new medical branch, radiotherapy, was
      developed.

PMID- 21905608
TI  - [Cardiopulmonary resuscitation through centuries].
AB  - THE ANCIENT TIMES: Many early civilisations left testimonies about ancient times
      and resuscitation, as well. Some of them did it successfully and some of them did
      it less successfully; however, all of them wished to help a dying person and to
      bring him back to life. The first trustworthy note can be found in the Bible--Old
      Testament as a very realistic description of resuscitation of a child. THE MIDDLE
      AGES: The medieval scientists, Paracelsus and Vesalius, described first
      successful resuscitation attempts in the 15th and 16th century. These two men
      successfully applied ventilation methods by air inflation with blacksmith
      bellows. THE MODERN ERA: The first defibrillation was recorded in the 18th
      century in England, which was conducted by one of the volunteer society members.
      With the development of mechanics and techniques, the first precursors of modern
      respirators were introduced in the 19th century. The age of modern
      cardiopulmonary resuscitation began in the middle of 20th century, when Dr Peter
      Safar brought in the combination of artificial ventilation and chest compressions
      as the standard for implementing resuscitation. Adrenalin and defibrillation were
      introduced into the resuscitation techniques by Dr Redding and Dr Kouwenhaven,
      respectively; thus beginning the advance life support administration, which has
      been applied, with minor changes, until today.

PMID- 21905609
TI  - [Prevalence of psychiatric disorders among homeless people in one area of Tokyo].
AB  - OBJECTIVES: This study is the first ever field survey in Japan of the prevalence
      of psychiatric disorders among homeless people in one area of Tokyo. The main aim
      of was to make accurate diagnoses by a psychiatrist to give an accurate picture.
      METHODS: The survey period was from December 30, 2008 to January 4, 2009. The
      people covered by the survey were people living on the streets within a one
      kilometer radius ofJR Ikebukuro Station in this period. The survey area was
      selected within Toshima City as a district where it would be possible to roughly
      grasp the total number of homeless people. The definition of homeless people in
      this study was the same as that which was stipulated in the Ministry of Health,
      Labor and Welfare national survey. A total of 115 people living on the streets
      received the written request to participate in the survey and 80 agreed to do so,
      beiung enrolled as the subjects of this study. Mini International
      Neuropsychiatric Interview (MINI) questionnaires and a separately created
      questionnaire that asked about the subjects' living circumstances were used in
      the interviews and finally, a psychiatrist made diagnoses of psychiatric
      disorders according to the Diagnostic and Statistical Manual of Mental Disorders,
      Fourth Edition, Text Revision (DSM-IV-TR) diagnosis standards. RESULTS: The
      average age of the subjects was 50.5 (standard deviation; 12.3) and there were 75
      men (93.8%) and 5 women (6.3%). 50 people (62.5%) were diagnosed with psychiatric
      disorders which included 33 people (41.3%) who had depression, 12 (15%) who were
      dependent on alcohol and 12 (15%) who had psychotic disorders such as
      hallucinations or delusions. Using the degree of risk in the MINI classification,
      45 (57.0%) were at risk of committing suicide and 25 people (31.6%) had already
      attempted suicide in the past. CONCLUSION: The representativeness of homeless
      people in Japan who have psychiatric disorders in this study is limited but that
      the finding of 62.5% of homeless people suffering from some symptoms and a high
      risk of suicide suggestss that this is an urgent issue for medical support.

PMID- 21905610
TI  - [Contribution of socioeconomic status to smoking behavior of parents of 4th grade
      elementary school students in Japan].
AB  - OBJECTIVES: The present study was performed to elucidate the effects of
      individual and social factors on smoking behavior of parents of fourth grade
      elementary school students in Japan. METHODS: A self-administered questionnaire
      was sent to a total of 4,179 households of fourth grade elementary school
      students. A total of 3,522 responses including actual numbers of children,
      smoking behavior of parents, and marital status were available for the analysis.
      RESULTS: Current smoking rate in mothers was 21.2%. In mothers, "smoking of
      spouse" "single mother", "under the age of 34", "not taking child-care leave;",
      "mother's parents not alive", "mothers from Chiba", "nursery use", "not use
      parenting circles", "unvaccinated measles or inoculation unknown" and "life
      dissatisfaction" were statistically associated with smoking behavior. The current
      smoking rate in fathers was 51.4%. Four factors of "smoking of spouse", "under
      the age of 34", "non-skilled labor, sales work" and "employees of private
      companies of less than 1,000 employees" were statistically associated with
      smoking behavior. CONCLUSION: The present study demonstrated a close link between
      smoking behavior and individual socioeconomic status in Japanese parents.
      Especially, smoking of spouse and being a single female parent were important
      factors for smoking.

PMID- 21905611
TI  - [Re-exploring attitude toward community scale and its relationship to health
      status among the general population].
AB  - OBJECTIVES: In order for community-based health promotion and prevention
      activities to be effective and efficient, it is important to assess the community
      consciousness among local residents. The purpose of this study was to review the
      reliability and validity of the Attitude toward Community Scale (ACS) and examine
      its association with health status among the general population. METHODS: A cross
      sectional survey was conducted in February 2009 using a mail-in self-administered
      questionnaire. The target population comprised 4,123 randomly-selected local
      residents aged 20 years and over living in Kashiwa city, Chiba prefecture, Japan.
      The questionnaire encompassed the ACS (the wording of some items was modified),
      an also included data to allow assessment of demographics and health status.
      RESULTS: Of 4,123 questionnaires, 1,735 could be analyzed (valid response rate:
      42.1%). Confirmatory factor analysis supported the two-factor model of the
      original scale. The reliability of the scale was verified using the Cronbach's
      alpha coefficient. All item-total correlations were moderately or strongly
      positive. Logistic regression showed that a better attitude toward the community
      was associated with higher self-rated health, less anxiety about the future and
      less loneliness. CONCLUSION: Although the original scale was developed in 1978,
      the ACS still appears applicable for modern research following some wording
      modifications of the items. In future studies, it will be necessary to clearly
      establish relationships between health status and community consciousness and to
      develop methodology for enhancing the latter.

PMID- 21905612
TI  - [Developing Japanese version of the eHealth Literacy Scale (eHEALS)].
AB  - OBJECTIVES: With the rapid developing an internet society, ehealth literacy,
      defined as the ability to seek, find, understand, and appraise and apply the
      knowledge gained to addressing or solving a health problem, becomes important to
      promote and aid health care at the individual level. However, the eHealth
      Literacy Scale (eHEALS) was only a scale developed to assess the ehealth
      literacy. Thus, the present study was conducted to evaluated the validity and
      reliability of a Japanese version of the eHEALS (J-eHEALS), and examine the
      association of ehealth literacy with demographic attributes and characteristics
      on health information searching among Japanese adults. METHODS: Data were
      analyzed for 3,000 Japanese adults (males: 50.0%,mean age: 39.6 + 10.9 years) who
      responded to an Internet-based cross-sectional survey. The J-eHEALS, 6
      demographic attributes, resources for obtaining health information (health
      resources), and contents of health information obtained from internet (ehealth
      contents) were obtained with a questionnaire. Confirmatory factor analysis and
      correlation with the communicative and critical health literacy scale were
      utilized to assess construct validity and criterion validity. Cronbach alpha and
      correlation coefficients were computed for internal consistency and test-retest
      reliability. Also, differences in J-eHEALS scores with each demographic attribute
      were examined with ANOVA and the independent t-test. Finally, chi-square tests
      were used to determine differences in the proportions of ehealth literacy groups
      (high or low) classified with a median split within health resources and ehealth
      contents. RESULTS: Principal components analysis produced a single factor
      solution and confirmatory factor analysis for the 8-items model demonstrated high
      indices (GFI = .988, CFI = .993, RMSEA= .056). A significant positive correlation
      was found between the J-eHEALS and communicative and critical health literacy
      scores. Cronbach alpha was 0.93 (P < .01), and test-retest reliability was r =
      0.63 (P < .01). The J-eHEALS scores were significantly higher in women, the 40
      and 50-year age group, those with high income, and individuals with a high
      frequency of internet searching. Furthermore, the high ehealth literacy group
      used many health resources and obtained a greater variety of ehealth contents as
      compared with the low literacy group. The most frequent resource was the internet
      in the high group, and television/radio in the low group. However, these results
      could be subject to bias because of the non-representative nature of the Internet
      population. CONCLUSION: The results indicate the J-eHEALS to be a highly
      validated and reliable scale. The present study suggests that enhancement of
      ehealth literacy will be important to utilize the increasing amount of health
      information on the internet effectively and appropriately.

PMID- 21905613
TI  - [Activities and awareness of public health nurses working at local government
      facilities and health centers regarding potential nuclear accidents].
AB  - OBJECTIVES: The purpose was to study public health service activities developed
      during non-emergency periods to respond to potential nuclear accidents and to
      contribute to an understanding of public health nurses' awareness of the
      possibility of such accidents. METHODS: For the purpose of this study, we chose
      prefectural health centers located in a prefecture with a nuclear power plant and
      in two adjacent prefectures, along with all local administrative bodies (cities,
      towns, and villages) in these prefectures. For each one of 124 entities, we
      selected one public health nurse in charge of health crisis management from among
      the personnel to be targeted for a questionnaire survey conducted by mail. The
      survey period was from October to November 2009, and the questionnaire contained
      questions on the following: whether there had been any disasters over the past
      ten years; whether the respondent had received training in public health services
      regarding nuclear accidents; and public health service activities developed
      during non-emergency periods to respond to potential nuclear accidents (and the
      amount of work done in this regard). RESULTS: The response rate for our survey
      was 71.8%. Of the total of 124 entities chosen, 9 were aware of the possibility
      of radiation accidents and 12 had manuals on radiation accidents. Two local
      governments and five health centers had participated in accident drills, and at
      both of two local governments, public health nurses were expected to act as
      guides during resident evacuation in the event of a nuclear accident. Public
      health nurses were sent to participate in workshops on radiation at four
      facilities located in the prefecture with a nuclear power plant. Our analysis
      revealed a lack of knowledge (beta = -0.404, P < 0.01) and concerns over one's
      own safety (beta = -0.233, P < 0.01) to have significant effects on the level of
      anxiety with regard to performing tasks as public health nurses in the event of
      disaster. CONCLUSION: The results of our survey lead us to believe that apart
      from creation of manuals, provision of opportunities to gain knowledge of
      materials regarding past damage to the health of residents and how such damage
      can be coped with is likely to be effective in developing effective measures in
      response to disasters.

PMID- 21905614
TI  - [Molecular mechanisms of zinc in prostate cancer].
AB  - In many developed countries, prostate cancer is the most common male tumour
      disease. The high incidence and mortality requires early diagnosis,
      differentiation of aggressive, highly malignant forms from clinically silent
      forms and understanding of the pathogenesis with its typical metabolic
      aberrancies (if any) in order to develop new targeted therapies. Prostate cells
      (including prostate cancer cells) are unique in their relation to zinc ions.
      Prostate tissue can accumulate these ions in up to tenfold higher concentration
      than other body cells. These ions influence many cellular processes incl.
      proliferation, differentiation and apoptosis. Prostate cancer cells lack ability
      to accumulate zinc. Therefore, zinc ions may be expected to play an important
      role in the disease pathogenesis, in its propagation and metastatic potential of
      tumour cells. Intracellular zinc levels are regulated by zinc-binding proteins,
      especially metallothioneins, and zinc transporters. Zinc level regulation
      dysfunction has been identified in prostate cancer cells and may thus play an
      important role in the prostate cancer pathogenesis. Moreover, due to its
      overproduction by prostate tissue, metallothionein serum levels are elevated and
      can be used as an important tumour marker.

PMID- 21905615
TI  - [Advances in clinical treatment of malignant melanoma: B-RAF kinase inhibition].
AB  - Malignant melanoma is an aggressive cancer of pigment-producing cells, derivates
      of the neural crest. Surgical resection is the most effective form of treatment
      during initial phases of the disease. Advanced stages are usually treated by
      adjuvant immunotherapy (interferon alpha) or dacarbazine + multiferon. Response
      and survival rates are extremely poor. The emerging approach of personalized
      medicine brings about significant advances in the treatment of melanoma. Apart
      from administration of imatinib for a small subgroup of melanomas harbouring KIT
      mutations, the most promising approach is the use of B-RAF kinase inhibitors. The
      previously tested RAF inhibitors (e.g. sorafenib) did not perform better compared
      to conventional chemotherapy or immunotherapy. However, the results are much more
      promising with the recently developed inhibitor PLX4032 (Plexxikon; RG7204, Roche
      Pharmaceuticals; vemurafenib). This inhibitor targets tumours harbouring B
      RAF(V600E) of B-RAF(V600K) activating mutations, which are present in 40-70% of
      malignant melanomas. An absence of the above mentioned activating mutations or
      parallel presence of activating RAS mutations (e.g. RAS(G12D)) should be used as
      contraindications. The use of PLX4032 provides better outcome than any of the
      currently used therapies, including partial or complete response recorded in 81%
      of patients, and prolonged median survival. Currently, this drug is being tested
      in phase II and III trials. The incidence of PLX4032-related adverse effects is
      relatively high; acquired resistance repeatedly occurring within several months
      of treatment may also represent a significant problem. Combined therapy is
      probably needed to further increase the complete response rate and to prolong
      survival. This should either include some of the currently used
      chemotherapeutics, or alternatively it may employ inhibitors of some of the
      kinases capable of stimulating the MEK and ERK kinases independently of B-RAF
      (e.g. COT). Nevertheless, even PLX4032 monotherapy should be viewed as a
      significant improvement of the current state-of-the-art treatment of malignant
      melanoma.

PMID- 21905616
TI  - [Palliative cancer care within the Hradec Kralove Region Health Care System: own
      experience].
AB  - Palliative cancer care is an active treatment and nursing intervention in
      patients in whom cancer therapy has been withdrawn due to untreatable progression
      of the cancer disease. The main aim of palliative cancer care is to ensure the
      best possible quality of life of a cancer patient and the patient's family
      members. Palliative cancer care is provided in two basic forms, general and
      specialized. In the present paper, the authors discuss palliative cancer care and
      its implementation into clinical practice with reference to their own experience
      in providing this care.

PMID- 21905617
TI  - [Schnitzler syndrome: diagnostics and treatment].
AB  - BACKGROUNDS: The most important diagnostic criteria for Schnitzler syndrome
      include chronic urticaria, the presence of monoclonal IgM immunoglobulin, marked
      inflammation (leukocytosis, elevated CRP and erythrocyte sedimentation rate),
      subfebrile temperatures or fevers and bone and joint pains. It is a rare
      idiopathic disease that may lead to potentially life-threatening complications
      such as development of secondary amyloidosis or transformation into malignant
      lymphoproliferation. Schnitzler syndrome should be included in differential
      diagnostics of chronic urticaria and fevers of unknown origin. The diagnostic
      algorithm is based on clinical presentation and serum and urine electrophoreses
      to detect monoclonal components. Blockade of interleukin-1 (IL-1), key cytokine
      in the pathogenesis of the disease, dominates current therapeutic protocols.
      Anakinra (Kineret), recombinant human IL-1 receptor antagonist, is the most
      widely used treatment option. According to literature, disease remission was
      obtained in all treated patients. Therefore, anakinra represents a significant
      diagnostic possibility to differentiate Schnitzler syndrome from e.g. monoclonal
      gammopathy of unknown significance (MGUS) associated with urticaria of different
      aetiology. Biological therapy with rilonacept (Arcalyst) and canakinumab (Ilaris)
      represents a new treatment alternative for patients, allowing prolonged dosing
      intervals of 1 and 8 weeks, respectively (compared to 24 hours with anakinra).
      The review article also presents findings of various imaging methods
      (conventional radiography, computed tomography, traditional bone scintigraphy)
      and photographs of patients with Schnitzler syndrome before and after anakinra
      therapy. DESIGN: The aim of the review is to draw attention to the existence of
      this rare autoinflammatory and potentially premalignant condition, present a
      simple diagnostic algorithm and provide an overview of therapeutic options for
      the patients. CONCLUSIONS: Malign potential of Schnitzler syndrome, possible
      development into systemic amyloidosis and the fact that patients are frequently
      referred to oncology clinics for differential diagnostics of monoclonal
      gammopathy, are the main reasons why clinical oncologists should be aware of
      Schnitzler syndrome.

PMID- 21905618
TI  - [Oropharyngeal mucositis--pain management].
AB  - Oropharyngeal mucositis is a clinically significant and painful complication of
      an intensive chemotherapy or head and neck radiotherapy. The management of a
      patient in risk of this complication must include appropriate and generally
      recommended prophylactic measures. An effective and safe treatment must be
      offered to patients who have developed oropharyngeal mucositis. The basic care
      involves local mouthwashes, sprays or viscous gels with variable effect on pain
      reduction. In more serious cases, tramadol and morphine are the drugs of choice;
      transdermal fentanyl or buprenorphine can be considered as an alternative. Pain
      management must be individualized.

PMID- 21905619
TI  - Low molecular weight heparins for thromboprophylaxis during induction
      chemotherapy in patients with multiple myeloma.
AB  - BACKGROUNDS: Patients with multiple myeloma have a high risk of venous
      thromboembolism (VTE), especially during the induction chemotherapy. The aim of
      our observational study was to determine the impact of prophylaxis with low
      molecular weight heparin (LMWH) on the incidence of thromboembolic complications.
      PATIENTS AND METHODS: We analyzed the incidence of thromboembolic events in 258
      patients treated with induction chemotherapy containing vincristin, doxorubicin
      or idarubicin, and dexamethasone, followed by stimulation chemotherapy with
      cyclophosphamide and G-CSF, and high-dose chemotherapy with melphalan. Two groups
      of these patients were compared based on the practice of thromboprophylaxis.
      Patients in the first group (Control, n = 140) were either not treated or treated
      with a short duration of anticoagulation therapy while the patients in the second
      group (Prophylactic, n = 118) underwent standard prophylaxis with LMWH throughout
      the entire period of induction chemotherapy. A total of 102 patients were
      selected for a close monitoring of the prophylactic effect of different LMWH
      doses and to be compared to patients without treatment. RESULTS: Standard
      prophylaxis with LMWH significantly (p < 0.007) lowered a risk of VTE when
      compared to patients without such prophylaxis (3.4% versus 12.9%, respectively).
      Furthermore, analysis of the subgroup of 102 patients revealed that higher LMWH
      doses (> 70 IU/kg per day) achieved full prophylaxis in 28 patients while lower
      doses were less effective leading to DVT in 3 (7.7%) out of 39 patients. In
      contrast, VTE was diagnosed in 5 (14.3%) out of 35 patients without any LMWH
      prophylaxis. CONCLUSION: Prophylaxis with LMWH leads to a significant reduction
      of the risk of thromboembolic complications during the induction chemotherapy in
      patients suffering from MM. The prophylactic effect of LMWH is dose-dependent.

PMID- 21905620
TI  - [Detection of circulating tumor cells from peripheral blood in patients with
      transitional cell carcinoma--pilot study. Comparison with the standard
      histopathological staging].
AB  - BACKGROUNDS: The aim of this pilot study was to investigate whether UP-II and
      EGFR genes expression detection with RT-PCR and the use of immunohistochemistry
      methods on patient samples taken before and after surgery could be used as a
      cancer marker for detection of circulating tumor cells in peripheral blood of
      patients with TCC. Another goal of this study was to identify whether surgery can
      influence the amount of circulating tumor cells and to correlate the samples with
      standard histopathological staging. MATERIALS AND METHODS: A total of 43 patients
      with histologically provenTTC was enrolled in the study. There were 33 men and 10
      women in the sample, mean age was 65 +/- 12 years (range 37-85 years). Forty
      (93.0%) patients had TCC of the urinary bladder, 2 (4.6%) had TCC of renal pelvis
      and 1 (2.3%) had TCC of urinary bladder, urethra, and renal pelvis. A sample of
      10 ml of peripheral blood was collected from each patient before and within 1
      hour after a surgery. Blood samples were used for immunomagnetic separation of
      circulating tumor cells and determination of UP-II and EGFR genes expression.
      Subsequently, cancer tissue was processed, endolymphatic, intravascular and
      peritoneal invasion determined and CK-7, CK-20, stromelysin, Ki-67 and p53
      expression evaluated. Blood samples taken before and after the surgery were also
      subjected to immunohistochemical analysis using hematoxylin-eosin (HE) staining
      and staining by Papanicolaus (PAP). CK-7 and CK-20 expression was also evaluated.
      RESULTS: EGFR and UP-II were expressed in 24 of the 35 (68.6%) and in 19 of the
      35 (54.3%) cancer tissues samples, respectively. EGFR was expressed neither in
      blood samples nor in immuno-separated cell samples. UP-II was expressed in 1 of
      the 19 (5.3%) samples of immuno-separated cells acquired before the surgery and
      in no sample of immuno-separated cells obtained after the surgery (P < 0.9999).
      Moreover, UP-II was expressed in 2 of the 32 (6.3%) whole blood samples taken
      before the surgery and in 3 out of 32 (9.4%) whole blood samples taken within an
      hour after the surgery (P < 0.9999). Histopathological examination showed TCC
      invasion in 11 of the 43 patients: 1 patient with intravascular, 6 with
      endolymphatic, 1 with intravascular and endolymphatic and 3 with intravascular,
      endolymphatic and perineural invasion. Immunohistochemical examination of
      separated blood before and after the surgery by PAP and HE staining, CK-7 and CK
      20 expression were negative in nearly all samples. Immunohistochemical
      examination ofTCC tissue showed positive results in 97.7% for CK-7expression,
      74.4% for CK-20 and 97.7% for stromelysin. Cytological examination of urine was
      positive in 19 (50%) patients and correlated well with higher grade G3 in 20
      (46.5%) patients. Ki-67 expression was significantly higher in patients with G3
      (31.15%) in comparison to patients with G1 (7.53%) (p < 0.01). There was no
      significant association between grade and expression of p53 and stromelysin in
      cancer tissue. CONCLUSION: Our preliminary tests did not show any significant
      change to EGFR and UP-II expression in peripheral blood and in immuno-separated
      cells before and after a surgery. The results for a group of patients with lower
      pTNM grade did not confirm the presence of malignant urothelial cells in
      peripheral blood.

PMID- 21905621
TI  - [Pulmonary metastases of the clear cell (conventional) renal cell carcinoma-
      options and results of surgical treatment].
AB  - BACKGROUNDS: At the diagnosis, up to one third of patients with clear cell
      (conventional) renal cell carcinoma have metastases, and the disease will
      progress in a half of patients with localized disease; the lungs are the most
      frequently affected organ. Despite clear advances in targeted biological
      treatment, radical surgery of organ, mainly pulmonary, metastases is a justified
      treatment approach with good results. AIM: A nine-year retrospective analysis of
      patients with clear cell renal cell carcinoma undergoing surgical treatment of
      pulmonary metastases. MATERIALS AND METHODS: At our centre, 13 patients with the
      mean age of 65 years, 9 of which were men, underwent surgical treatment between
      2001 and 2009. Surgery was only indicated in patients after renal tumour
      resection without extrapulmonary metastases in whom presurgical assessment
      suggested that the pulmonary metastases were resectable (with respect to their
      number and location) and in whom the benefits of performing the surgery
      outweighed any potential risks. Metastases were solitary in 9 patients and
      multiple in the rest, 2 patients had bilateral involvement. Median disease-free
      interval following nephrectomy was 28 months. RESULTS: A total of 11 unilateral
      and 2 bilateral resections were performed during one or two surgical operations.
      Most frequently, wedge resection was performed (7 patients). A total of 23
      metastases were resected. Perisurgical morbidity was 15.4%, zero mortality. Of
      those undergoing metastasectomy, 53.8% are still surviving with a median survival
      of 24.3 months. Three-year survival in the sample was 66%, 5-year survival was
      53%. Five patients (38.5%) have had no disease progression for a median of 8.8
      months. CONCLUSION: Our results confirm the positive role of metastasectomy in
      the treatment of pulmonary metastases of clear cell (conventional) renal cell
      carcinoma. Long-term survival after pulmonary metastasectomy might be expected in
      patients with solitary metachrone small metastases with DFI after nephrectomy > 1
      year, without tumour involvement of the relevant lymph nodes and R0 resection.

PMID- 21905622
TI  - [The role of procalcitonin in the differential diagnosis of fever in patiens with
      multiple myeloma].
AB  - Fever and elevated C-reactive protein are frequently found in hematooncological
      patients. It is sometimes difficult to distinguish between infectious fever and
      drug-related or tumour-associated fever. Tumour-related fever is not very common
      in multiple myeloma (unlike malignant lymphomas). C-reactive protein (CRP) is
      usually elevated simultaneously with fever and so it cannot be used in
      differential diagnosis of febrile states. There is another marker that provides
      information about the origins of the fever--rocalcitonin. We present cases of
      three patients that illustrate the significance of procalcitonin in patients with
      multiple myeloma.

PMID- 21905623
TI  - [Psychological support for cancer care professionals: contemporary theory and
      practice within the Czech Healthcare System].
AB  - Health care professionals, especially those working in cancer care, represent a
      subgroup of helping professions that requires special psychological care. Recent
      findings clearly show that a lack of regular psychological care for oncologists
      and oncology nurses leads to higher rate of psychiatric and physical illness,
      poorer quality of life, higher employee fluctuation rates and lower quality of
      provided medical care. In spite of this, the special psychological care for
      cancer care professionals is still lacking and theoretical and practical level of
      their undergraduate and postgraduate education in psychology does not satisfy the
      demands of clinical practice. Regular group meetings seem to be an effective way
      of psychological care. They provide an opportunity for the participants to view
      own problems from a distance and to seek new options. It allows them to gain new
      insights from the discussed situations and to get support or feedback from
      colleagues. Regular group meetings also represent a key component of self-care
      and it is an important preventive factor of exhaustion that has been shown to
      cause medical or personal misconducts. In this context, the aim of the present
      paper is to describe the basic theoretical background for regular group meetings
      of oncologists and oncology nurses and to refer about the current practice within
      the Czech health care system.

PMID- 21905624
TI  - [The year 2011 is the year of melanoma: Melanoma Forum, Frankfurt, 19 May 2011].

PMID- 21905625
TI  - Staphylococcal cassette chromosome mec (Sccmec) classification and typing
      methods: an overview.
AB  - Meticillin-resistant Staphylococcus aureus (MRSA) is one of the main causes of
      hospital-acquired infections, but since late 1990s also the community-acquired.
      For better understanding of the S.aureus epidemiology there is an urgent need for
      creation of new typing method for SCCmec element. The molecular typing of MRSA
      for epidemiological purposes is investigated by pulsed-field gel electrophoresis
      (PFGE), multilocus sequence typing (MLST), spa typing and the SCCmec type
      assignment. In last few years not only new type of SCCmec (VI to XI) have been
      identified, but also additional subtypes (i.e. IVg-j) and different variants of
      already existed one (i.e. 5C2&5 and 2B2&5) were discovered. The aim of this
      review is to briefly summarize current knowledge about SCCmec classification and
      to discuss advantages and disadvantages of selected SCCmec typing methods.

PMID- 21905626
TI  - Immobilized cells of recombinant Escherichia coli strain for continuous
      production of L-aspartic acid.
AB  - For L-aspartic acid biosynthesis, high production cells of Escherichia coli
      mutant B-715 and P1 were immobilized in chitosan gel using a technique developed
      in our laboratory. The immobilization process reduced initial activity of the
      intact cells, however, the biocatalyst produced was very stabile for long-term
      use in multi-repeated batch or continuous processes. Temperature influence on the
      conversion of ammonium fumarate to L-aspartic acid was investigated. In long-term
      experiments, over 603 hours, the temperature 40 degrees C was found to be the
      best for both biocatalyst stability and high conversion rate. The optimum
      substrate concentration was 1.0 M. Continuous production of L-aspartic acid was
      investigated in three types of column bioreactors characterized by different
      volumes as well as different high to biocatalyst bed volume rations (Hz/Vz). The
      highest conversion rate, 99.8%, and the productivity 6 g/g/h (mass of L-aspartic
      acid per dry mass of cells in biocatalyst per time unit) was achieved in the
      bioreactor with the highest value Hz/Vz = 3.1, and liquid hour space velocity
      value of 5.2, defined as the volume of feeding substrate passed per volume of
      catalyst in bioreactor per one hour.

PMID- 21905627
TI  - Reaction conditions for maximal cyclodextrin production by cyclodextrin
      glucanotransferase from Bacillus megaterium.
AB  - The effect of the reaction conditions (substrate concentration, enzyme dosage,
      and pH) on cyclodextrin production by cyclodextrin glucanotransferase from
      Bacillus megaterium was investigated by applying mathematical modeling methods.
      Adequate models were developed and they were used for determination of the
      optimal conditions for maximal formation of beta-cyclodextrins at minimal
      concentrations of a- and gamma-cydclodextrins. The main factor affecting the
      ratio of the products was pH of the reaction mixture. At pH 9 the enzyme formed
      mainly beta- and y-cyclodextrins and the ratio a:beta:gamma was 2.6:83.5:13.9; at
      pH 5 the ratio changed to 8.6:84.6:6.8. Mathematical models were used for
      determination of the conditions for maximal conversion of the substrate into
      cyclodextrins. 45.88% conversion of starch was achieved at 5% substrate
      concentration, 3.5 U/g enzyme dosage, and pH 7.4.

PMID- 21905628
TI  - Efficacy of UV treatment in the management of bacterial adhesion on hard
      surfaces.
AB  - The efficacy of UV treatment to control bacterial adhesion onto hard surfaces was
      investigated in laboratory conditions. The major characteristics necessary for
      biofilm formation like extracellular polymeric substance (EPS) production,
      carbohydrate and protein concentration in EPS, and adhesion ability onto hard
      surface were studied using two bacterial strains isolated from marine biofilms.
      The results showed that there was a considerable difference between the control
      and UV treated bacterial cultures in their viability, production of EPS, and
      adhesion ability. The protein and carbohydrate concentration of the EPS and the
      adhesion of bacterial cells to surface were also considerably reduced due to UV
      treatment. This study indicates that treatment of water with UV light may be used
      to control biofilm development on hard surfaces.

PMID- 21905629
TI  - Comparison of the nucleotide sequences of wheat dwarf virus (WDV) isolates from
      Hungary and Ukraine.
AB  - Wheat dwarf virus (WDV) is the most ubiquitous virus in cereals causing huge
      losses in both Hungary and Ukraine. The presence of barley-and wheat-adapted
      strains has been confirmed, suggesting that the barley strain is restricted to
      barley, while the wheat strain is present in both wheat and barley plants. Five
      WDV isolates from wheat plants sampled in Hungary and Ukraine were sequenced and
      compared with known WDV isolates from GenBank. Four WDV isolates belonged to the
      wheat strain. Our results indicate that WDV-Odessa is an isolate of special
      interest since it has originated from wheat, but belongs to the barley-adapted
      strain, providing novel data on WDV biology and raising issues of pathogen
      epidemiology.

PMID- 21905631
TI  - Utilization of UF-permeate for production of beta-galactosidase by lactic acid
      bacteria.
AB  - Four lactobacilli strains (Lactobacillus bulgaricus, Lactobacillus acidophilus,
      Lactobacilus casei and Lactobacillus reuteri) were grown in MRS broth and three
      lactococci strains (Streptococcus thermophilus, Lactococcus lactis subsp. Lactis
      and Lactococcus lactis subsp. lactis biovar. diacetilactis) were grown in M17
      broth. L. reuteri and S. thermophilus were chosen on the basis of the best mean
      beta-galactosidase activity of 10.44 and 10.01 U/ml respectively, for further
      studies on permeate-based medium. The maximum production of beta-galactosidase by
      L. reuteri was achieved at lactose concentration of 6%, initial pH 5.0-7.5,
      ammonium phosphate as nitrogen source at a concentration of 0.66 g N/L and
      incubation temperature at 30 degrees C/24 hrs to give 6.31 U/ml. While in case of
      S. thermophilus, maximum beta-galactosidase production was achieved at 10%
      lactose concentration of permeate medium, supplemented with phosphate buffer
      ratio of 0.5:0.5 (KH2PO4:K2HPO4, g/L), at initial pH 6.0-6.5, ammonium phosphate
      (0.66g N/L) as nitrogen source and incubation temperature 35 degrees C for 24 hrs
      to give 7.85 U/ml.

PMID- 21905630
TI  - Beta-glucanase productivity improvement via cell immobilization of recombinant
      Escherichia coli cells in different matrices.
AB  - The studies have been performed to analyze the production of beta-glucanase by a
      recombinant strain of Escherichia coli immobilized in different matrices. Porous
      sintered glass SIRAN, Ceramic supporting matrices and Broken Pumice stone as well
      as SIRAN Raschig-rings were examined for the immobilization of whole bacterial
      cells. The beta-glucanase activity of bacteria immobilized in CeramTec PST 5 (4-5
      mm) was very low. CeramTec PST 5 (1.5-2.5 mm) was found to be the best carrier
      compared to all other matrices regarding glucanase production (630 U/ml) and
      compared to enzyme activity produced by free cells (500 U/ml). Different doses of
      matrices were applied (2, 5, 7, 10 g/lask) in the form of "matrix weight". Using
      2 g/flask of CeramTec PST 5 (1.5-2.5 mm) yielded enzyme activity of 630 U/ml).
      CeramTec gives highest operational stability of beta-glucanase by repeated batch
      fermentation to 5 cycles, and activity reached 660 U/ml. Scanning electron
      microscopy observations showed a high number of vegetative cells that continued
      growth inside the matrices, indicating that beta-glucanase activity improvement
      was due to the immobilization of the cells.

PMID- 21905632
TI  - Strains differentiation of Microsporum canis by RAPD analysis using (GACA)4 and
      (ACA)5 primers.
AB  - Molecular analysis of dermatophytes (based on PCR fingerprinting) revealed high
      clonal differentiation between the genus and species. Microsporum canis
      (zoophilic dermatophyte, belonging to genus Microsporum), responsible for most
      cases of tinea capitis in children, tinea corporis in adults and dermatophytoses
      in cats, is very unique in comparison with other dermatophytes. Results of most
      molecular studies show that there is no clonal differentiation within M. canis as
      distinct from other species. The aim of this study was application of (GACA)4
      repetitive primer and (ACA)5 primer for typing of M. canis strains isolated from
      human and animals in Central Poland. Fungal strains: 32 clinical isolates of M.
      canis, originated from patients from Central Poland; 11 strains isolated from
      infected cats (6) and dogs (7), reference strains of M. canis (CBS 113480), T
      rubrum (CBS 120358), T mentagrophytes (CBS 120357) and E. floccosum (CBS 970.95).
      The genomic DNAs of the strains were used as a template in RAPD reaction. No
      differentiation was observed for the analyzed M. canis strains using (GACA)4 and
      (ACA)5 typing.

PMID- 21905633
TI  - SDS-PAGE heat-shock protein profiles of environmental Aeromonas strains.
AB  - Aeromonas microorganisms normally grow at temperatures between 5 degrees C and 45
      degrees C and therefore should have high thermotolerance. Thus it was of interest
      to find out whether A. hydrophila, A. caviae and A. veronii biovar sobria
      serovars respond to abrupt temperature changes with a heat shock-like response.
      To this end the present study was undertaken to determine whether Aeromonas
      species exhibits a heat shock response to different temperatures and time
      factors. The response of Aeromonas serovars to 24 h and 48 h of thermal stress at
      25 degrees C, 42 degrees C and 50 degrees C involved the synthesis of 12-18 heat
      shock proteins (HSPs) bands with molecular weights ranging between 83.5-103.9 kDa
      in the high HSP molecular mass and 14.5-12.0 as low molecular mass HSP.
      Electrophoretic analysis of the HSPs showed that the serovars do not cluster very
      tightly and also that they are distinct from each other.

PMID- 21905634
TI  - Species-specific sensitivity of coagulase-negative Staphylococci to single
      antibiotics and their combinations.
AB  - The activity of beta-lactam antibiotics (oxacillin, cloxacillin, cephalotin),
      vancomycin, gentamicin and rifampicin applied in vitro individually and in
      combination against 37 nosocomial methicillin-resistant strains of coagulase
      negative staphylococci (CNS) was assessed to demonstrate the heterogeneity of
      this group of bacteria and estimate the chance of the efficacy of such therapy.
      The strains belonged to four species: Staphylococcus epidermidis, Staphylococcus
      haemolyticus, Staphylococcus cohnii, Staphylococcus hominis. They originated from
      a hospital environment and from the skin of medical staff of the intensive care
      unit of a paediatric ward at a university hospital. All strains were methicillin
      resistant, according to CLSI standards, but individual strains differed in
      MIC(ox) values. Susceptibility to other tested antibiotics was also
      characteristic for the species. The increased susceptibility to antibiotics in
      combinations, tested by calculating the fractional inhibitory concentration (FIC)
      index, concerned 26 out of 37 investigated strains and it was a feature of a
      particular species. Combinations of vancomycin and cephalotin against S.
      epidermidis and oxacillin with vancomycin were significant, as well as cephalotin
      and rifampicin in growth inhibition of multiresistant S. haemolyticus strains.

PMID- 21905635
TI  - Association between existence of integrons and multi-drug resistance in
      Acinetobacter isolated from patients in southern Iran.
AB  - Nosocomial infections caused by multi-drug resistant Acinetobacter pose a serious
      problem in many countries. This study aimed at determining the antibiotic
      susceptibility patterns and prevalence of different classes of integrons in
      isolated Acinetobacter. In addition, the association between production of
      specific bands in PCR assay and magnitude of multi-drug resistance was
      investigated. In total, 88 Acinetobacter strains were isolated from patients from
      October 2008 through September 2009. The Minimal inhibitory concentration (MIC)
      of 12 antibiotics conventionally used in clinics against the isolates, was
      determined by E-test method. The existence of integron classes was investigated
      by PCR assay through the amplification of integrase genes. The most effective
      antibiotic against Acinetobacter was colistin with 97.7% activity, followed by
      imipenem (77.3%) and meropenem (72.7%). The presence ofintegron classes 1 and 2
      in 47 (53.4%) isolates was confirme, However, no class 3 was detected. The
      proportion of class 1, compared with class 2, was high (47.7% vs. 3.4%). The
      association between multi-drug resistance to norfloxacin, ceftazidime,
      gentamicin, ciprofloxacin, cefepime and amikacin and the presence of integrons
      was statistically significant. However, the association was not remarkable in
      many of the isolates which exhibited resistance to the rest of antibiotics. This
      may imply that in addition to integrons, other resistance determinants such as
      transposon and plasmid may also contribute to resistance. To reduce the pressure
      on sensitive isolates, comprehensive control measures should be implemented.
      Furthermore, wise application of effective antibiotics could help alleviate the
      situation. Colistin is the most effective antibiotic in vitro against
      Acinetobacter.

PMID- 21905636
TI  - Dissemination of class 1, 2 and 3 integrons among different multidrug resistant
      isolates of Acinetobacter baumannii in Tehran hospitals, Iran.
AB  - A total of 100 non-duplicate Acinetobacter baumannii isolates were collected from
      different hospitals in Tehran and were confirmed as A. baumannii by conventional
      biochemical and API testing. Antimicrobial susceptibility of these isolates was
      checked by a disk diffusion method in accordance with CLSI guidelines. The
      isolates were then detected as carrying class 1 and 2 integron gene cassettes by
      PCR evaluation and then genotyped by REP-PCR. More than 50% (n = 50) of the
      isolates were multidrug resistant. The results showed that more than 80% of all
      multidrug resistant A. baumannii strains carry a class 1 integron. Distribution
      of IntI 1 and IntI2 among A. baumannii isolates was 58% and 14%, respectively.
      Analysis of a conserved segment of class 1 integron showed a range from 100 bp to
      2.5 kb. REP-PCR fingerprinting showed more than 20 genotypes among A. baumannii
      strains. TIhere was no relationship between REP genotypes and the distribution of
      different classes of integrons. This is a comprehensive study on the distribution
      of different classes of integrons among A. baumannii in Iran. Considering the
      exact role of integrons in coding drug resistance in bacteria, the findings of
      this study could help us find antimicrobial resistant mechanisms among A.
      baumannii isolates in Iran.

PMID- 21905637
TI  - Host response to the presence of Helicobacter spp. DNA in the liver of patients
      with chronic liver diseases.
AB  - Literature data indicate an association between the presence of Helicobacter spp.
      in the liver and the development of hepatocellular carcinoma (HCC). However, the
      role of H. pylori infections in chronic liver diseases (CLD) remains
      controversial. The aim of this study was to detect Helicobacter spp. DNA in
      patients with CLD, and to investigate the host response to the presence of the
      bacterium in the liver. Helicobacter spp. DNA was detected in 59% samples.
      H.pylori was the most prevalent species (94%). We estimated the expression level
      of IL-1 and IL-8 genes. The presence of Helicobacter spp. did not have a
      significant effect on the gene expression of IL-8 and IL-1.

PMID- 21905638
TI  - Dehydrogenative Diels-Alder reaction.
AB  - The dehydrogenative cycloaddition of dieneynes, which possess a diene in the form
      of a styrene moiety and a dienophile in the form of an alkyne moiety, produces
      naphthalene derivatives when heated. It was found that a key requirement of this
      process is the presence of a silyl group attached to the alkyne moiety, which
      forces a dehydrogenation reaction to occur.

PMID- 21905639
TI  - Efficient, single-step access to imidazo[1,5-a]pyridine n-heterocyclic carbene
      precursors.
AB  - The three-component coupling reaction of substituted picolinaldehydes, amines,
      and formaldehyde to produce imidazo[1,5-a]pyridinium ions is reported, providing
      an efficient method for the preparation of N-heterocyclic carbenes (NHCs).
      Reactions proceed in high yields under mild conditions, allowing the
      incorporation of diverse functionality and chiral substituents. Higher order
      condensations are also described that provide access to multidentate NHC ligands
      useful for a variety of applications.

PMID- 21905641
TI  - Simultaneous determination of phenolic compounds and saponins in quinoa
      (Chenopodium quinoa Willd) by a liquid chromatography-diode array detection
      electrospray ionization-time-of-flight mass spectrometry methodology.
AB  - A new liquid chromatography methodology coupled to a diode array detector and a
      time-of-flight mass spectrometer has been developed for the simultaneous
      determination of phenolic compounds and saponins in quinoa (Chenopodium quinoa
      Willd). This method has allowed the simultaneous determination of these two
      families of compounds with the same analytical method for the first time. A fused
      core column C18 has been used, and the analysis has been performed in less than
      27 min. Both chromatographic and electrospray ionization time-of-flight mass
      spectrometry parameters have been optimized to improve the sensitivity and to
      maximize the number of compounds detected. A validation of the method has also
      been carried out, and free and bound polar fractions of quinoa have been studied.
      Twenty-five compounds have been tentatively identified and quantified in the free
      polar fraction, while five compounds have been tentatively identified and
      quantified in the bound polar fraction. It is important to highlight that 1-O
      galloyl-beta-D-glucoside, acacetin, protocatechuic acid 4-O-glucoside,
      penstebioside, ethyl-m-digallate, (epi)-gallocatechin, and canthoside have been
      tentatively identified for the first time in quinoa. Free phenolic compounds have
      been found to be in the range of 2.746-3.803 g/kg of quinoa, while bound phenolic
      compounds were present in a concentration that varies from 0.139 and 0.164 g/kg.
      Indeed, saponins have been found to be in a concentration that ranged from 5.6 to
      7.5% of the total composition of whole quinoa flour.

PMID- 21905640
TI  - Preparation of nucleosides derived from 2-nitroimidazole and D-arabinose, D
      ribose, and D-galactose by the Vorbruggen method and their conversion to
      potential precursors for tracers to image hypoxia.
AB  - 2-Nitroimidazole was silylated using hexaethyldisilazane and then reacted with 1
      O-acetyl derivatives of D-arabinose, D-ribose, and D-galactose in acetonitrile at
      mild temperatures (-20  degrees C to rt), catalyzed by triethylsilyl triflate
      (Vorbruggen conditions). The alpha-anomer was formed in the former case and the
      beta-anomers in the latter two cases (highly) selectively. When D-arabinose and D
      ribose were silylated with tert-butyldiphenylsilyl chloride in pyridine at the
      hydroxyl groups at C-5 and acetylated at the other ones in a one-pot reaction,
      mixtures of anomeric 1-O-acetyl derivatives were obtained. These were coupled by
      the Vorbruggen method and then deblocked at C-5 and tosylated to give precursors
      for tracers to image hypoxia in four steps without using Hg(CN)(2) necessary for
      other methods. The Vorbruggen conditions enable a shorter route to azomycin
      nucleoside analogues than the previous coupling procedures.

PMID- 21905642
TI  - Fourier transform near-infrared spectroscopy application for sea salt quality
      evaluation.
AB  - Near-infrared (NIR) spectroscopy in diffuse reflectance mode was explored with
      the objective of discriminating sea salts according to their quality type
      (traditional salt vs "flower of salt") and geographical origin (Atlantic vs
      Mediterranean). Sea salts were also analyzed in terms of Ca(2+), Mg(2+), K(+),
      alkalinity, and sulfate concentrations to support spectroscopic results. High
      concentrations of Mg(2+) and K(+) characterized Atlantic samples, while a high
      Ca(2+) content was observed in traditional sea salts. A partial least-squares
      discriminant analysis model considering the 8500-7500 cm(-1) region permitted the
      discrimination of salts by quality types. The regions 4650-4350 and 5900-5500 cm(
      1) allowed salts classification according to their geographical origin. It was
      possible to classify correctly 85.3 and 94.8% of the analyzed samples according
      to the salt type and to the geographical origin, respectively. These results
      demonstrated that NIR spectroscopy is a suitable and very efficient tool for sea
      salt quality evaluation.

PMID- 21905643
TI  - Leader peptide-directed processing of labyrinthopeptin A2 precursor peptide by
      the modifying enzyme LabKC.
AB  - Lantibiotics are peptide antibiotics, realizing their unique secondary structure
      by posttranslational modifications, the most important one being the formation of
      the characteristic amino acid lanthionine. Like other ribosomal peptide
      antibiotics, they are synthesized with an N-terminal leader peptide important for
      posttranslational processing by modifying enzymes; after peptide maturation, the
      leader peptide is proteolytically cleaved off. Numerous studies of the leader
      peptides of class I and II lantibiotics already showed their crucial role in
      recognition, self-immunity, and extracellular transport. The recently described
      labyrinthopeptins, members of the family of class III lantibiotics, exhibit the
      characteristic novel amino acid labionin, which was revealed by elucidation of
      the structure of labyrinthopeptin A2. The assembly of the labionin motif in the
      linear peptide chain is mediated by the lyase-kinase-cyclase-type enzyme LabKC
      through a serine side chain phosphorylation with GTP, elimination of the
      phosphate group, and a subsequent 2-fold Michael-type addition cyclization. In
      this work, we systematically investigated for the first time the importance of
      the leader peptide in the processing of class III lantibiotics using the example
      of the labyrinthopeptin A2 precursor peptide. In vitro studies with synthetic
      leader peptide analogues revealed that a conserved N-terminal hydrophobic patch
      on a putative helical structure is required for the proper peptide processing by
      the modifying enzyme LabKC. On the other hand, studies showed that the C-terminal
      part of the leader peptide serves as a spacer between the binding site and active
      sites for phosphorylation and elimination, thus restricting the number of hydroxy
      amino acid side chains that could undergo dehydration. Finally, a model for the
      peptide recognition and processing by the LabKC has been postulated.

PMID- 21905644
TI  - Selective enzymatic degradation of self-assembled particles from amphiphilic
      block copolymers obtained by the combination of N-carboxyanhydride and nitroxide
      mediated polymerization.
AB  - Combining controlled radical polymerizations and a controlled polypeptide
      synthetic technique, such as N-carboxyanhydride (NCA) ring-opening
      polymerization, enables the generation of well-defined block copolymers to be
      easily accessible. Here we combine NCA polymerization with the nitroxide-mediated
      radical polymerization of poly(n-butyl acrylate) (PBA) and polystyrene (PS),
      using a TIPNO and SG1-based bifunctional initiator to create a hybrid block
      copolymer. The polypeptide block consists of (block) copolymers of poly(L
      glutamic acid) embedded with various quantities of L-alanine. The formed
      superstructures (vesicles and micelles) of the block copolymers possessed varying
      degrees of enzyme responsiveness when exposed to elastase and thermolysin,
      resulting in controlled enzymatic degradation dictated by the polypeptide
      composition. The PBA containing block copolymers possessing 50% L-alanine in the
      polypeptide block showed a high degradation response compared to polymers
      containing lower L-alanine quantities. The particles stabilized by copolypeptides
      with L-alanine near the hydrophobic block showed full degradation within 4 days.
      Particles containing polystyrene blocks revealed no appreciable degradation under
      the same conditions, highlighting the specificity of the system and the
      importance of synthetic polymer selection. However, when the degradation
      temperature was increased to 70  degrees C, degradation could be achieved due to
      the higher block copolymer exchange between the particle and the solution. A
      number of novel biohybrid structures are disclosed that show promise as enzyme
      responsive materials with potential use as payload release vehicles, following
      their controlled degradation by specific, target, enzymes.

PMID- 21905646
TI  - Fast carbon dioxide fixation by 2,6-pyridinedicarboxamidato-nickel(II)-hydroxide
      complexes: influence of changes in reactive site environment on reaction rates.
AB  - The planar complexes [Ni(II)(pyN(2)(R2))(OH)](-), containing a terminal hydroxo
      group, are readily prepared from N,N'-(2,6-C(6)H(3)R(2))-2,6
      pyridinedicarboxamidate(2-) tridentate pincer ligands (R(4)N)(OH), and
      Ni(OTf)(2). These complexes react cleanly and completely with carbon dioxide in
      DMF solution in a process of CO(2) fixation with formation of the bicarbonate
      product complexes [Ni(II)(pyN(2)(R2))(HCO(3))](-) having eta(1)-OCO(2)H ligation.
      Fixation reactions follow second-order kinetics (rate = k(2)'[Ni(II)-OH][CO(2)])
      with negative activation entropies (-17 to -28 eu). Reactions were monitored by
      growth and decay of metal-to-ligand charge-transfer (MLCT) bands at 350-450 nm.
      The rate order R = Me > macro > Et > Pr(i) > Bu(i) > Ph at 298 K (macro =
      macrocylic pincer ligand) reflects increasing steric hindrance at the reactive
      site. The inherent highly reactive nature of these complexes follows from k(2)' ~
      10(6) M(-1) s(-1) for the R = Me system that is attenuated by only 100-fold in
      the R = Ph complex. A reaction mechanism is proposed based on computation of the
      enthalpic reaction profile for the R = Pr(i) system by DFT methods. The R = Et,
      Pr(i), and Bu(i) systems display biphasic kinetics in which the initial fast
      process is followed by a slower first order process currently of uncertain
      origin.

PMID- 21905647
TI  - Observation of inductive effects that cause a change in the rate-determining step
      for the conversion of rhenium azides to imido complexes.
AB  - The cationic oxorhenium(V) complex [Re(O)(hoz)(2)(CH(3)CN)][B(C(6)F(5))(4)] [1;
      Hhoz = 2-(2'-hydroxyphenyl)-2-oxazoline] reacts with aryl azides (N(3)Ar) to give
      cationic cis-rhenium(VII) oxoimido complexes of the general formula
      [Re(O)(NAr)(hoz)(2)][B(C(6)F(5))(4)] [2a-2f; Ar = 4-methoxyphenyl, 4
      methylphenyl, phenyl, 3-methoxyphenyl, 4-chlorophenyl, and 4
      (trifluoromethyl)phenyl]. The kinetics of formation of 2 in CH(3)CN are first
      order in both azide (N(3)Ar) and oxorhenium(V) complex 1, with second-order rate
      constants ranging from 3.5 * 10(-2) to 1.7 * 10(-1) M(-1) s(-1). A strong
      inductive effect is observed for electron-withdrawing substituents, leading to a
      negative Hammett reaction constant rho = -1.3. However, electron-donating
      substituents on phenyl azide deviate significantly from this trend. Enthalpic
      barriers (DeltaH(?)) determined by the Eyring-Polanyi equation are in the range
      14-19 kcal mol(-1) for all aryl azides studied. However, electron-donating 4
      methoxyphenyl azide exhibits a large negative entropy of activation, DeltaS(?) = 
      21 cal mol(-1) K(-1), which is in sharp contrast to the near zero DeltaS(?)
      observed for phenyl azide and 4-(trifluoromethyl)phenyl azide. The Hammett linear
      free-energy relationship and the activation parameters support a change in the
      mechanism between electron-withdrawing and electron-donating aryl azides. Density
      functional theory predicts that the aryl azides coordinate via N(alpha) and
      extrude N(2) directly. For the electron-withdrawing substituents, N(2) extrusion
      is rate-determining, while for the electron-donating substituents, the rate
      determining step becomes the initial attack of the azide. The barriers for these
      two steps are inverted in their order with respect to the Hammett sigma values;
      thus, the Hammett plot appears with a break in its slope.

PMID- 21905645
TI  - Reactions of the fluorescent sensor, Zinquin, with the zinc-proteome: adduct
      formation and ligand substitution.
AB  - Zinquin (ZQ) is a commonly used sensor for cellular Zn(2+) status. It has been
      assumed that it measures accessible Zn(2+) concentrations in the nanomolar range.
      Instead, this report shows a consistent pattern across seven mammalian cell and
      tissue types that ZQ reacts with micromolar concentrations of Zn(2+) bound as Zn
      proteins. The predominant class of products were ZQ-Zn-protein adducts that were
      characterized in vivo and in vitro by a fluorescence emission spectrum centered
      at about 470 nm, by their migration over Sephadex G-75 as protein not low
      molecular weight species, by the exclusion of reaction with lipid vesicles, and
      by their large aggregate concentration. In addition, variable, minor formation of
      Zn(ZQ)(2) with a fluorescence band at about 490 nm was observed in vivo in each
      case. Because incubation of isolated Zn-proteome with ZQ also generated similar
      amounts of Zn(ZQ)(2), it was concluded that this species had formed through
      direct ligand substitution in which ZQ had successfully competed for protein
      bound Zn(2+). Parallel studies with the model Zn-proteins, alcohol dehydrogenase
      (ADH), and alkaline phosphatase (AP) revealed a similar picture of reactivity:
      ZQ(ACID) (Zinquin acid, (2-methyl-8-p-toluenesulfonamido-6-quinolyloxy)acetate))
      able to bind to one Zn(2+) and extract the other in Zn(2)-ADH, whereas it removed
      one Zn(2+) from Zn(2)-AP and did not bind to the other. Zinquin ethyl ester
      (ethyl(2-methyl-8-p-toluenesulfonamido-6-quinolyloxy)acetate); ZQ(EE)) bound to
      both proteins without sequestering Zn(2+) from either one. In contrast to a
      closely related sensor, 6-methoxy-8-p-toluenesulfonamido-quinoline (TSQ), neither
      ZQ(ACID) nor ZQ(EE) associated with Zn-carbonic anhydrase. A survey of reactivity
      of these sensors with partially fractionated Zn-proteome confirmed that ZQ and
      TSQ bind to distinct, overlapping subsets of the Zn-proteome.

PMID- 21905648
TI  - A low-energy-gap organic dye for high-performance small-molecule organic solar
      cells.
AB  - A novel donor-acceptor-acceptor (D-A-A) donor molecule, DTDCTB, in which an
      electron-donating ditolylaminothienyl moiety and an electron-withdrawing
      dicyanovinylene moiety are bridged by another electron-accepting 2,1,3
      benzothiadiazole block, has been synthesized and characterized. A vacuum
      deposited organic solar cell employing DTDCTB combined with the electron acceptor
      C(70) achieved a record-high power conversion efficiency (PCE) of 5.81%. The
      respectable PCE is attributed to the solar spectral response extending to the
      near-IR region and the ultracompact absorption dipole stacking of the DTDCTB thin
      film.

PMID- 21905649
TI  - On the reversibility of environmental contamination with persistent organic
      pollutants.
AB  - An understanding of the factors that control the time trends of persistent
      organic pollutants (POPs) in the environment is required to evaluate the
      effectiveness of emission reductions and to predict future exposure. Using a
      regional contaminant fate model, CoZMo-POP 2, and a generic bell-shaped emission
      profile, we simulated time trends of hypothetical chemicals with a range of POP
      like partitioning and degradation properties in different compartments of a
      generic warm temperate environment, with the objective of identifying the
      processes that may prevent the reversibility of environmental contamination with
      POPs after the end of primary emissions. Evaporation from soil and water can
      prevent complete reversibility of POP contamination of the atmosphere after the
      end of emissions. However, under the selected conditions, only for organic
      chemicals within a narrow range of volatility, that is, a logarithm of the
      octanol air equilibrium partition coefficient between 7 and 8, and with
      atmospheric degradation half-lives in excess of a few month can evaporation from
      environmental reservoirs sustain atmospheric levels that are within an order of
      magnitude of those resulting from primary emissions. HCB and alpha-HCH fulfill
      these criteria, which may explain, why their atmospheric concentrations have
      remained relatively high decades after their main primary emissions have been
      largely eliminated. Soil-to-water transfer is found responsible for the lack of
      reversibility of POP contamination of the aqueous environment after the end of
      emissions, whereas reversal of water-sediment exchange, although possible, is
      unlikely to contribute significantly. Differences in the reversibility of
      contamination in air and water suggests the possibility of changes in the
      relative importance of various exposure pathways after the end of primary
      emissions, namely an increase in the importance of the aquatic food chain
      relative to the agricultural one, especially if the former has a benthic
      component. Since simulated time trends were strongly dependent on degradation
      half-lives, partitioning properties and selected environmental input parameters,
      it should not be surprising, that different field studies often generate highly
      divergent time trends.

PMID- 21905650
TI  - Synthesis and antifungal activity of natural product-based 6-alkyl-2,3,4,5
      tetrahydropyridines.
AB  - Seven 6-alkyl-2,3,4,5-tetrahydropyridines (5a-5g) that mimic the natural
      piperideines that were recently identified in fire ant venom have been
      synthesized. Compounds 5c-5g with C-6 alkyl chain lengths from C14 to C18 showed
      varying degrees of antifungal activities, with 5e (6-hexadecyl-2,3,4,5
      tetrahydropyridine) and 5f (6-heptadecyl-2,3,4,5-tetrahydropyridine) being the
      most active. Compound 5e exhibited minimum fungicidal concentrations of 3.8,
      15.0, 7.5, and 7.5 MUg/mL against Cryptococcus neoformans, Candida albicans,
      Candida glabrata, and Candida krusei, respectively. The antifungal activities of
      these compounds appear to be associated with the C-6 side chain length. This
      study represents the first effort to evaluate antifungal activities of synthetic
      analogues of the newly identified fire ant venom alkaloids.

PMID- 21905651
TI  - Unusual catalytic effect of the two-dimensional molecular space with regular
      triphenylphosphine groups.
AB  - A novel organic-inorganic hybrid 2D molecular space with regular
      triphenylphosphine groups (triphenylphosphineamidephenylsilica, PPh(3)APhS) was
      successfully synthesized through grafting triphenylphosphine groups in the 2D
      structure of layered aminophenylsilica dodecyl sulfate (APhTMS-DS), which was
      developed in our previous research, with regular ammonium groups. The 2D
      structures were kept after the grafting reaction of triphenylphosphine groups in
      PPh(3)APhS. The catalytic potentials of 2D molecular space with regular
      triphenylphosphine groups were investigated. An unusual catalytic effect was
      found in a carbon-phosphorus ylide reaction. The PPh(3)-catalyzed reaction of
      modified allylic compounds, including bromides and chlorides with tropone yielded
      a [3 + 6] annulation product. However, an unusual [8 + 3] cycloadduct was
      obtained in the reaction of modified allylic compounds, including bromides and
      chlorides with tropone catalyzed by PPh(3)APhS. Otherwise, the stable catalytic
      intermediate was successfully separated, and the reaction activity of the
      catalytic intermediate was confirmed in the reaction of modified allylic
      compounds with tropone catalyzed by PPh(3)APhS. This research is the first
      successful example of directly influencing catalytic reaction processes and
      product structures by utilizing the chemical and geometrical limits of 2D
      molecular spaces with regular catalyst molecules and affords a novel method for
      controlling catalytic reaction processes and catalyst design.

PMID- 21905652
TI  - Development of active polyvinyl alcohol/beta-cyclodextrin composites to scavenge
      undesirable food components.
AB  - Active food packaging systems based on the incorporation of agents into polymeric
      package walls are being designed to purposely release or retain compounds to
      maintain or even increase food quality. The objective of this work was to develop
      polyvinyl alcohol (PVOH)/beta-cyclodextrin (betaCD) composite films that can be
      applied to reduce undesirable component content such as cholesterol in foods
      through active retention of the compounds in the package walls during storage.
      Cyclodextrins were added to PVOH in a proportion of 1:1 and cross-linked with
      glyoxal under acidic media to reduce its water-soluble character. Three different
      cross-linking procedures were used: cross-linking of the polymer/polysaccharide
      mixture in solution and film casting, PVOH. betaCD*; cross-linking of the
      polymer, addition of betaCD, and casting of the mixture, PVOH*.CD; and casting of
      a PVOH film, addition of a betaCD/glyoxal solution onto the film, and cross
      linking during drying, PVOH.CD*. Characterization studies showed that the
      PVOH*.CD and PVOH.CD* films provided the best physical characteristics with the
      lowest release values and the highest barrier properties. As a potential
      application, materials were tested as potential cholesterol-scavenging films.
      There was a significant reduction in the cholesterol concentration in milk
      samples when they were exposed to the materials developed.

PMID- 21905654
TI  - Phenolic compounds in hawthorn (Crataegus grayana) fruits and leaves and changes
      during fruit ripening.
AB  - Phenolics in the fruits and leaves of  Crataegus grayana  were identified by HPLC
      UV-ESI-MS. The contents of these compounds and their changes during autumn were
      also analyzed. Epicatechin [1-7 mg/g dry mass (DM) in fruits and 1-10 mg/g DM in
      leaves), procyanidins B2 (2-4 and 1-8 mg/g DM) and C1 (2-4 and 1-8 mg/g DM),
      hyperoside (0.5-1 and 2-11 mg/g DM), and a quercetin-pentoside (0.3-0.5 and 2-6
      mg/g DM) were the major phenolics in both fruits and leaves. C-Glycosyl flavones
      were present in leaves (2-5 mg/g DM), whereas only trace levels were found in
      fruits. Ideain and 5-O-caffeoylquinic acid were found only in fruits. An
      additional 11 phenolics were identified/tentatively identified. Total phenolic
      contents reached highest levels by the end of August in fruits and by the end of
      September in leaves. The compositional profiles of phenolics in fruits and leaves
      of C. grayana were different from those of other Crataegus species.

PMID- 21905653
TI  - Natural tubule clay template synthesis of silver nanorods for antibacterial
      composite coating.
AB  - Halloysite is naturally available clay mineral with hollow cylindrical geometry
      and it is available in thousands of tons. Silver nanorods were synthesized inside
      the lumen of the halloysite by thermal decomposition of the silver acetate, which
      was loaded into halloysite from an aqueous solution by vacuum cycling. Images of
      individual ca. 15 nm diameter silver nanorods and nanoparticles were observed
      with TEM. The presence of silver inside the tubes was also verified with STEM-EDX
      elemental mapping. Nanorods had crystalline nature with [111] axis oriented ~68
      degrees  from the halloysite tubule main axis. The composite of silver nanorods
      encased in clay tubes with the polymer paint was prepared, and the coating
      antimicrobial activity combined with tensile strength increase was demonstrated.
      Coating containing up 5% silver loaded halloysite did not change color after
      light exposure contrary to the sample prepared with loading with unshelled silver
      nanoparticles. Halloysite tube templates have a potential for scalable
      manufacturing of ceramic encapsulated metal nanorods for composite materials.

PMID- 21905655
TI  - Capillary electrophoresis of free fatty acids by indirect ultraviolet detection:
      application to the classification of vegetable oils according to their botanical
      origin.
AB  - A method for the determination of fatty acids in vegetable oils by capillary
      electrophoresis with indirect UV-vis detection has been developed. The separation
      of fatty acids was optimized in terms of Brij surfactant nature and concentration
      and organic modifier (2-propanol) percentage. The optimal background electrolyte
      consisted of 10 mM p-hydroxybenzoate, 5 mM Tris at pH 8.8, 80 mM Brij 98, 40%
      acetonitrile, and 10% 2-propanol. Under these conditions, vegetable oils from
      five botanical origins (avocado, corn, extra virgin olive, hazelnut, and soybean)
      were analyzed and the fatty acid contents established. Linear discriminant
      analysis (LDA) models were constructed using fatty acid peak areas as predictors.
      An excellent resolution among all category pairs was obtained, and all samples
      were correctly classified with assignment probabilities of >95%.

PMID- 21905656
TI  - Dynamic multicrop model to characterize impacts of pesticides in food.
AB  - A new dynamic plant uptake model is presented to characterize health impacts of
      pesticides applied to food crops, based on a flexible set of interconnected
      compartments. We assess six crops covering a large fraction of the worldwide
      consumption. Model estimates correspond well with observed pesticide residues for
      12 substance-crop combinations, showing residual errors between a factor 1.5 and
      19. Human intake fractions, effect and characterization factors are provided for
      use in life cycle impact assessment for 726 substance-crop combinations and
      different application times. Intake fractions typically range from 10-2 to 10-8
      kg(intake) kg(applied)-1. Human health impacts vary up to 9 orders of magnitude
      between crops and 10 orders of magnitude between pesticides, stressing the
      importance of considering interactions between specific crop-environments and
      pesticides. Time between application and harvest, degradation half-life in plants
      and residence time in soil are driving the evolution of pesticide masses.We
      demonstrate that toxicity potentials can be reduced up to 99% by defining
      adequate pesticide substitutions. Overall, leafy vegetables only contribute to 2%
      of the vegetal consumption, but due to later application times and higher intake
      fractions may nevertheless lead to impacts comparable or even higher than via the
      larger amount of ingested cereals.

PMID- 21905657
TI  - Structural characterization of guaiacyl-rich lignins in flax (Linum
      usitatissimum) fibers and shives.
AB  - The structural characteristics of the lignins from flax (Linum usitatissimum)
      fibers and shives were studied. Significant differences in the content and
      composition of the lignin from both parts were observed. The lignin contents were
      3.8% in the fibers and 29.0% in the shives. Analysis by Py-GC/MS indicated a
      H:G:S molar ratio of 13:72:15 in the milled wood lignin (MWL) isolated from flax
      fibers and a molar ratio of 5:87:8 in the MWL isolated from flax shives. In
      addition, 2D-NMR showed a predominance of beta-O-4' aryl ether linkages, followed
      by beta-5' phenylcoumaran and beta-beta' resinol-type linkages in both MWLs, with
      a higher content of condensed linkages in flax shives. Thioacidolysis (followed
      by Raney nickel desulfurization) gave further information on the lignin units
      involved in the different linkages and confirmed the enrichment of G units. The
      thioacidolysis dimers released were similar from both lignins, with a
      predominance of the beta-5' followed by beta-1' and 5-5' structures.

PMID- 21905658
TI  - Hydrothermal etching assisted crystallization: a facile route to functional yolk
      shell titanate microspheres with ultrathin nanosheets-assembled double shells.
AB  - We report a facile "hydrothermal etching assisted crystallization" route to
      synthesize Fe(3)O(4)@titanate yolk-shell microspheres with ultrathin nanosheets
      assembled double-shell structure. The as-prepared microspheres possess a uniform
      size, tailored shell structure, good structural stability, versatile ion-exchange
      capability, high surface area, large magnetization, and exhibit a remarkable
      catalytic performance.

PMID- 21905659
TI  - Novel heterotetranuclear V2Mo2 or V2W2 complexes with 4,4'-di-tert-butyl-2,2'
      bipyridine: syntheses, crystal structures, and catalytic activities.
AB  - Two novel heterotetranuclear complexes [V(2)O(2)(MU-MeO)(2)(MU-WO(4))(2)(4,4'
      (t)Bubpy)(2)] (1) and [V(2)O(2)(MU-MeO)(2)(MU-MoO(4))(2)(4,4'-(t)Bubpy)(2)] (2)
      were synthesized, and the solid state structures of these complexes were revealed
      by single crystal X-ray crystallography. The heterotetranuclear complexes 1 and 2
      are centrosymmetric building blocks, considered as consisting of two [VO(4,4'
      (t)Bubpy)](3+) units bridged by MU-MO(4)(2-) (M = W or Mo) anions connected with
      methoxy groups. Furthermore, catalytic activities of 1 and 2 in the alcohol
      oxidation with hydrogen peroxide as terminal oxidants in water as solvent were
      investigated.

PMID- 21905660
TI  - Biomagnification of perfluorinated compounds in a remote terrestrial food chain:
      Lichen-Caribou-wolf.
AB  - The biomagnification behavior of perfluorinated carboxylates (PFCAs) and
      perfluorinated sulfonates (PFSAs) was studied in terrestrial food webs consisting
      of lichen and plants, caribou, and wolves from two remote northern areas in
      Canada. Six PFCAs with eight to thirteen carbons and perfluorooctane sulfonate
      (PFOS) were regularly detected in all species. Lowest concentrations were found
      for vegetation (0.02-0.26 ng/g wet weight (ww) sum (Sigma) PFCAs and 0.002-0.038
      ng/g ww PFOS). Wolf liver showed highest concentrations (10-18 ng/g ww SigmaPFCAs
      and 1.4-1.7 ng/g ww PFOS) followed by caribou liver (6-10 ng/g ww SigmaPFCAs and
      0.7-2.2 ng/g ww PFOS). Biomagnification factors were highly tissue and substance
      specific. Therefore, individual whole body concentrations were calculated and
      used for biomagnification and trophic magnification assessment. Trophic
      magnification factors (TMF) were highest for PFCAs with nine to eleven carbons
      (TMF = 2.2-2.9) as well as PFOS (TMF = 2.3-2.6) and all but perfluorooctanoate
      were significantly biomagnified. The relationship of PFCA and PFSA TMFs with the
      chain length in the terrestrial food chain was similar to previous studies for
      Arctic marine mammal food web, but the absolute values of TMFs were around two
      times lower for this study than in the marine environment. This study
      demonstrates that challenges remain for applying the TMF approach to studies of
      biomagnification of PFCAs and PFSAs, especially for terrestrial animals.

PMID- 21905661
TI  - Measurements of isoprene-derived organosulfates in ambient aerosols by aerosol
      time-of-flight mass spectrometry-part 2: temporal variability and formation
      mechanisms.
AB  - Organosulfate species have recently gained attention for their potentially
      significant contribution to secondary organic aerosol (SOA); however, their
      temporal behavior in the ambient atmosphere has not been probed in detail. In
      this work, organosulfates derived from isoprene were observed in single particle
      mass spectra in Atlanta, GA during the 2002 Aerosol Nucleation and
      Characterization Experiment (ANARChE) and the 2008 August Mini-Intensive Gas and
      Aerosol Study (AMIGAS). Real-time measurements revealed that the highest
      organosulfate concentrations occurred at night under a stable boundary layer,
      suggesting gas-to-particle partitioning and subsequent aqueous-phase processing
      of the organic precursors played key roles in their formation. Further analysis
      of the diurnal profile suggests possible contributions from multiple production
      mechanisms, including acid-catalysis and radical-initiation. This work highlights
      the potential for additional SOA formation pathways in biogenically influenced
      urban regions to enhance the organic aerosol burden.

PMID- 21905662
TI  - Sonoproduction of liposomes and protein particles as templates for delivery
      purposes.
AB  - The development of nano and micro delivery systems (DS), so small in size, is
      growing in importance, such as in drug targeting. In an era where nano is the new
      trend, micro and nano materials are in the forefront of progress. These systems
      can be produced by a diversity of methods. However, the use of high-intensity
      ultrasound offers an easy and versatile tool for nano- and microstructured
      materials that are often unavailable by conventional methods. Similarly to the
      synthesis methods that can be used, several starting materials can be applied to
      produce particulate systems. In this review, the recent strategic development of
      DS is discussed with emphasis on liposomes and polymer-based, specially protein
      based, nanomedicine platforms for drug delivery. Among the variety of
      applications that materials in the particulate form can have, the control release
      of drugs is probably the most prominent one, as these have been in the forefront
      line of interest for biomedical applications. The basic concepts of sonochemical
      process pertaining to DS are summarized as well as the role of sonochemical
      procedure to their preparation. The different applications of these systems wrap
      up this review.

PMID- 21905663
TI  - Acid-activatable prodrug nanogels for efficient intracellular doxorubicin
      release.
AB  - Endosomal pH-activatable doxorubicin (DOX) prodrug nanogels were designed,
      prepared, and investigated for triggered intracellular drug release in cancer
      cells. DOX prodrugs with drug grafting contents of 3.9, 5.7, and 11.7 wt %
      (denoted as prodrugs 1, 2, and 3, respectively) were conveniently obtained by
      sequential treatment of poly(ethylene glycol)-b-poly(2-hydroxyethyl methacrylate
      co-ethyl glycinate methacrylamide) (PEG-b-P(HEMA-co-EGMA)) copolymers with
      hydrazine and doxorubicin hydrochloride. Notably, prodrugs 1, 2, and 3 formed
      monodispersed nanogels with average sizes of 114.4, 75.3, and 66.3 nm,
      respectively, in phosphate buffer (PB, 10 mM, pH 7.4). The in vitro release
      results showed that DOX was released rapidly and nearly quantitatively from DOX
      prodrug nanogels at endosomal pH and 37  degrees C in 48 h, whereas only a minor
      amount (ca. 20% or less) of drug was released at pH 7.4 under otherwise the same
      conditions. Confocal laser scanning microscope (CLSM) observations revealed that
      DOX prodrug nanogels delivered and released DOX into the cytosols as well as cell
      nuclei of RAW 264.7 cells following 24 h incubation. MTT assays demonstrated that
      prodrug 3 had pronounced cytotoxic effects to tumor cells following 72 h
      incubation with IC(50) data determined to be 2.0 and 3.4 MUg DOX equiv/mL for RAW
      264.7 and MCF-7 tumor cells, respectively. The corresponding polymer carrier, PEG
      b-P(HEMA-co-GMA-hydrazide), was shown to be nontoxic up to a tested concentration
      of 1.32 mg/mL. These endosomal pH-activatable DOX prodrug nanogels uniquely
      combining features of water-soluble macromolecular prodrugs and nanogels offer a
      promising platform for targeted cancer therapy.

PMID- 21905664
TI  - Gold-catalyzed 1,2-difunctionalizations of aminoalkynes using only N- and O
      containing oxidants.
AB  - We report two viable routes for the 1,2-difunctionalization of aminoalkynes using
      only oxidants. In the presence of a gold catalyst, nitrones enable the
      oxoamination of aminoalkynes 1 to form 2-aminoamides 2. With a suitable gold
      catalyst, nitrosobenzenes implement an alkyne/nitroso metathesis of the same
      substrates to give 2-oxoiminylamides 3. These two novel oxidations also provide
      1,2-aminoalcohols with opposite regioselectivity via NaBH(4) reduction in situ.

PMID- 21905666
TI  - Atomic-scale visualization of initial growth of homoepitaxial SrTiO3 thin film on
      an atomically ordered substrate.
AB  - The initial homoepitaxial growth of SrTiO(3) on a (?13 * ?13)-R33.7 degrees 
      SrTiO(3)(001) substrate surface, which can be prepared under oxide growth
      conditions, is atomically resolved by scanning tunneling microscopy. The
      identical (?13 * ?13) atomic structure is clearly visualized on the deposited
      SrTiO(3) film surface as well as on the substrate. This result indicates the
      transfer of the topmost Ti-rich (?13 * ?13) structure to the film surface and
      atomic-scale coherent epitaxy at the film/substrate interface. Such atomically
      ordered SrTiO(3) substrates can be applied to the fabrication of atom-by-atom
      controlled oxide epitaxial films and heterostructures.

PMID- 21905665
TI  - Thermodynamic analysis of protein-ligand interactions in complex biological
      mixtures using a shotgun proteomics approach.
AB  - Shotgun proteomics protocols are widely used for the identification and/or
      quantitation of proteins in complex biological samples. Described here is a
      shotgun proteomics protocol that can be used to identify the protein targets of
      biologically relevant ligands in complex protein mixtures. The protocol combines
      a quantitative proteomics platform with a covalent modification strategy, termed
      Stability of Proteins from Rates of Oxidation (SPROX), which utilizes the
      denaturant dependence of hydrogen peroxide-mediated oxidation of methionine side
      chains in proteins to assess the thermodynamic properties of proteins and protein
      ligand complexes. The quantitative proteomics platform involves the use of
      isobaric mass tags and a methionine-containing peptide enhancement strategy. The
      protocol is evaluated in a ligand binding experiment designed to identify the
      proteins in a yeast cell lysate that bind the well-known enzyme cofactor, beta
      nicotinamide adenine dinucleotide (NAD+). The protocol is also used to
      investigate the protein targets of resveratrol, a biologically active ligand with
      less well-understood protein targets. A known protein target of resveratrol,
      cytosolic aldehyde dehydrogenase, was identified in addition to six other
      potential new proteins targets including four that are associated with the
      protein translation machinery, which has previously been implicated as a target
      of resveratrol.

PMID- 21905667
TI  - Enhancing the intestinal membrane permeability of zanamivir: a carrier mediated
      prodrug approach.
AB  - The purpose of this study was to improve the membrane permeability and oral
      absorption of the poorly permeable anti-influenza agent, zanamivir. The poor oral
      bioavailability is attributed to the high polarity (cLogP ~ -5) resulting from
      the polar and zwitterionic nature of zanamivir. In order to improve the
      permeability of zanamivir, prodrugs with amino acids were developed to target the
      intestinal membrane transporter, hPepT1. Several acyloxy ester prodrugs of
      zanamivir conjugated with amino acids were synthesized and characterized. The
      prodrugs were evaluated for their chemical stability in buffers at various pHs
      and for their transport and tissue activation by enzymes. The acyloxy ester
      prodrugs of zanamivir were shown to competitively inhibit [(3)H]Gly-Sar uptake in
      Caco-2 cells (IC(50): 1.19 +/- 0.33 mM for L-valyl prodrug of zanamivir). The L
      valyl prodrug of zanamivir exhibited ~3-fold higher uptake in transfected
      HeLa/hPepT1 cells compared to wild type HeLa cells, suggesting, at least in part,
      carrier mediated transport by the hPepT1 transporter. Further, enhanced
      transcellular permeability of prodrugs across Caco-2 monolayer compared to the
      parent drug (P(app) = 2.24 * 10(-6) +/- 1.33 * 10(-7) cm/s for L-valyl prodrug of
      zanamivir), with only parent zanamivir appearing in the receiver compartment,
      indicates that the prodrugs exhibited both enhanced transport and activation in
      intestinal mucosal cells. Most significantly, several of these prodrugs exhibited
      high intestinal jejunal membrane permeability, similar to metoprolol, in the in
      situ rat intestinal perfusion system, a system highly correlated with human
      jejunal permeability. In summary, this mechanistic targeted prodrug strategy, to
      enhance oral absorption via intestinal membrane carriers such as hPepT1, followed
      by activation to parent drug (active pharmaceutical ingredient or API) in the
      mucosal cell, significantly improves the intestinal epithelial cell permeability
      of zanamivir and has the potential to provide the high oral bioavailability
      necessary for oral zanamivir therapy.

PMID- 21905668
TI  - Controlled clockwise-counterclockwise motion of the ring-shaped microtubules
      assembly.
AB  - The microtubule (MT)-kinesin system has been proposed as the building block of
      biomolecular motor based artificial biomachines. Considerable efforts have been
      devoted to integrate this system that produced a variety of ordered structures
      including the ring-shaped MT assembly which is being considered as a promising
      candidate for the further development of the biomachines. However, lack of proper
      knowledge that might help tune the direction of motion of ring-shaped microtubule
      assembly from counterclockwise to clockwise direction, and vice versa,
      significantly restricted their potential applications. We report our success in
      controlling the direction of rotational motion of ring-shaped MT assembly by
      altering the preparation conditions of microtubules. The change in the direction
      of rotation of MT rings could be interpreted in terms of the accompanied
      structural rearrangement of the MT lattice. For achieving handedness-regulated
      efficient biomachines having tunable asymmetric property, our study will be
      significantly directive.

PMID- 21905669
TI  - Discovery of isoxazole analogues of sazetidine-A as selective alpha4beta2
      nicotinic acetylcholine receptor partial agonists for the treatment of
      depression.
AB  - Depression, a common neurological condition, is one of the leading causes of
      disability and suicide worldwide. Standard treatment, targeting monoamine
      transporters selective for the neurotransmitters serotonin and noradrenaline, is
      not able to help many patients that are poor responders. This study advances the
      development of sazetidine-A analogues that interact with alpha4beta2 nicotinic
      acetylcholine receptors (nAChRs) as partial agonists and that possess favorable
      antidepressant profiles. The resulting compounds that are highly selective for
      the alpha4beta2 subtype of nAChR over alpha3beta4-nAChRs are partial agonists at
      the alpha4beta2 subtype and have excellent antidepressant behavioral profiles as
      measured by the mouse forced swim test. Preliminary absorption, distribution,
      metabolism, excretion, and toxicity (ADMET) studies for one promising ligand
      revealed an excellent plasma protein binding (PPB) profile, low CYP450-related
      metabolism, and low cardiovascular toxicity, suggesting it is a promising lead as
      well as a drug candidate to be advanced through the drug discovery pipeline.

PMID- 21905670
TI  - Predictive models for cytochrome p450 isozymes based on quantitative high
      throughput screening data.
AB  - The human cytochrome P450 (CYP450) isozymes are the most important enzymes in the
      body to metabolize many endogenous and exogenous substances including
      environmental toxins and therapeutic drugs. Any unnecessary interactions between
      a small molecule and CYP450 isozymes may raise a potential to disarm the
      integrity of the protection. Accurately predicting the potential interactions
      between a small molecule and CYP450 isozymes is highly desirable for assessing
      the metabolic stability and toxicity of the molecule. The National Institutes of
      Health Chemical Genomics Center (NCGC) has screened a collection of over 17,000
      compounds against the five major isozymes of CYP450 (1A2, 2C9, 2C19, 2D6, and
      3A4) in a quantitative high throughput screening (qHTS) format. In this study, we
      developed support vector classification (SVC) models for these five isozymes
      using a set of customized generic atom types. The CYP450 data sets were randomly
      split into equal-sized training and test sets. The optimized SVC models exhibited
      high predictive power against the test sets for all five CYP450 isozymes with
      accuracies of 0.93, 0.89, 0.89, 0.85, and 0.87 for 1A2, 2C9, 2C19, 2D6, and 3A4,
      respectively, as measured by the area under the receiver operating characteristic
      (ROC) curves. The important atom types and features extracted from the five
      models are consistent with the structural preferences for different CYP450
      substrates reported in the literature. We also identified novel features with
      significant discerning power to separate CYP450 actives from inactives. These
      models can be useful in prioritizing compounds in a drug discovery pipeline or
      recognizing the toxic potential of environmental chemicals.

PMID- 21905671
TI  - Quinoxalino[2,3-c]cinnolines and their 5-N-oxide: alkoxylation of methyl
      substituted quinoxalino[2,3-c]cinnolines to acetals and orthoesters.
AB  - We report the alkoxylation of methyl-substituted quinoxalino[2,3-c]cinnolines to
      give acetals and orthoesters in high yields. Routes to the precursors of this
      alkoxylation reaction as well as other quinoxalino[2,3-c]cinnoline and their 5
      oxide derivatives are reported. Most of these quinoxalino[2,3-c]cinnolines were
      prepared by cyclization of the corresponding 2-amino-3-(2
      nitrophenyl)quinoxaline, which, in turn, result from an unusual Beirut reaction
      from benzofurazan oxides plus 2-nitrobenzylcyanides. Mechanistic explanations for
      these intriguing reactions are presented.

PMID- 21905672
TI  - Bolaform superamphiphile based on a dynamic covalent bond and its self-assembly
      in water.
AB  - We have employed a dynamic covalent bond to fabricate a bolaform superamphiphile,
      which can be used as building blocks for controlled assembly and disassembly. In
      alkaline environment, one building block bearing a benzoic aldehyde group can
      react with the other building block bearing an amino group to form a bolaform
      superamphiphile. It is found that the bolaform superamphiphiles can self-assemble
      in water to form micellar aggregates. When the pH is tuned down to slightly
      acidic values, the benzoic imine bond can be hydrolyzed, leading to the
      dissociation of the superamphiphile. The micellar aggregates will also
      disassemble, and the loaded guest molecules are released subsequently. This line
      of research has enriched the family of bolaform amphiphiles, and the resulting
      assemblies may find application in the field of controlled and targetable drug
      delivery in a biological environment.

PMID- 21905673
TI  - Selective derivatization of cytosine and methylcytosine moieties with 2
      bromoacetophenone for submicrogram DNA methylation analysis by reversed phase
      HPLC with spectrofluorimetric detection.
AB  - In eukaryotes, actual DNA methylation patterns provide biologically important
      information, for which both, genome-wide and locus-specific methylation at
      cytosine residues have been extensively studied. The original contribution of
      this work relies on the selective derivatization of cytosine moieties with 2
      bromoacetophenone for the determination of global DNA methylation by reversed
      phase high performance liquid chromatography with spectrofluorimetric detection.
      The important features of the proposed procedure are as follows: (1) no need for
      the elimination of RNA, (2) detection limits for cytidine, 2'-deoxycytidine, 5
      methylcytidine, and 5-methyl-2'-deoxycytidine in the range of 14.4-22.7 fmol, (3)
      feasibility for the detection of 0.06% of methylation in a low amount of DNA (80
      ng), (4) potential viability for the evaluation of RNA methylation, and (5)
      relative simplicity in terms of analytical instrumentation and personnel
      training. The results obtained in the analysis of salmon testes DNA and nucleic
      acids from plant, human blood, and earthworms demonstrate the utility of the
      proposed procedure in biological studies and, in particular, for evaluation of
      the potential effect of environmental factors on actual DNA methylation in
      different types of living organisms.

PMID- 21905674
TI  - Cu2+-induced micellar charge selective fluorescence response of acridine orange:
      effect of micellar charge, pH, and mechanism.
AB  - Photophysical properties of cationic Acridine Orange (AO) have been studied in
      different micellar environments [anionic SDS (sodium dodecyl sulfate), nonionic
      TX (TritonX-100), and cationic CTAB (cetyl trimethyl ammonium bromide)] at
      different pH, in the presence of a metal ion (Cu(2+)). At pH ~ 8, addition of
      Cu(2+) results in AO fluorescence quenching in the presence of SDS micelle,
      enhancement of the same in the presence of TX micelle, and remaining unaltered in
      the presence of CTAB micelle. At pH ~ 2, addition of Cu(2+) results in AO
      fluorescence quenching only in the presence of SDS micelle, and it remains mostly
      unaffected in the presence of TX and CTAB. Availability of Cu(2+) toward AO and
      binding of Cu(2+) with AO at the charged micellar interface are responsible for
      this pH-dependent Cu(2+)-mediated micellar charge selective fluorescence pattern.

PMID- 21905675
TI  - Electrospray ionization tandem mass spectrometry analysis of the reactivity of
      structurally related bromo-methyl-benzoquinones toward oligonucleotides.
AB  - We report the use of electrospray ionization tandem mass spectrometry (ESI-MS/MS)
      as a tool for rapid screening of structurally related chemicals toward
      oligonucleotides using the binding of five bromobenzoquinones with single
      stranded (ss) and double-stranded (ds) oligonucleotides (ODNs) as a model. We
      found that these compounds interact differentially with oligonucleotides
      depending on the extent of their bromination and methylation. Three
      dibromobenzoquinones, 2,6-dibromo-1,4-benzoquinone (2,6-DBBQ), 2,5-dibromo-1,4
      benzoquinone (2,5-DBBQ), and 2,5-dimethyl-3,6-dibromo-1,4-benzoquinone (DMDBBQ),
      bound to ssODN to form 1:1 adducts, and the binding constant of DMDBBQ bound to
      ssODN was 100-fold lower than those of 2,6-DBBQ and 2,5-DBBQ to ssODN, indicating
      that methyl groups hindered interactions of the bromoquinones with ODNs.
      Collision-induced dissociation (CID) of the 1:1 and 1:2 adducts of ODN with 2,6
      DBBQ and 2,5-DBBQ demonstrated neutral loss of DBBQ and charge separations.
      Incubation of two tetrabromobenzoquinones (TBBQ), 2,3,5,6-tetrabromo-1,4
      benzoquinone and 3,4,5,6-tetrabromo-1,2-benzoquinone, with the same ODNs did not
      form any adducts of TBBQ with ssODN or dsODN; however, bromide-ODNs were
      detected. Fragmentation of the bromide-ODN adducts showed loss of the HBr
      molecule, supporting the presence of bromide on ODNs. High-resolution MS and
      MS/MS analysis of the mixtures of dinucleotides (AA, GG, CC, and TT) and TBBQ
      confirmed the presence of bromide on the dinucleotides, supporting the transfer
      of bromide to ODNs through interaction with TBBQ. This study presents evidence of
      differential interactions of structurally related bromo and methyl-benzoquinones
      with oligonucleotides and demonstrates a potential application of ESI-MS/MS
      analysis of chemical interactions with ODN for rapid screening of the reactivity
      of other structurally related environmental contaminants toward DNA.

PMID- 21905676
TI  - Oligomeric structure of ExbB and ExbB-ExbD isolated from Escherichia coli as
      revealed by LILBID mass spectrometry.
AB  - Energy-coupled transporters in the outer membrane of Escherichia coli and other
      Gram-negative bacteria allow the entry of scarce substrates, toxic proteins, and
      bacterial viruses (phages) into the cells. The required energy is derived from
      the proton-motive force of the cytoplasmic membrane, which is coupled to the
      outer membrane via the ExbB-ExbD-TonB protein complex. Knowledge of the structure
      of this complex is required to elucidate the mechanisms of energy harvesting in
      the cytoplasmic membrane and energy transfer to the outer membrane transporters.
      Here we solubilized an ExbB oligomer and an ExbB-ExbD subcomplex from the
      cytoplasmic membrane with the detergent undecyl maltoside. Using laser-induced
      liquid bead ion desorption mass spectrometry (LILBID-MS), we determined at
      moderate desorption laser energies the oligomeric structure of ExbB to be mainly
      hexameric (ExbB(6)), with minor amounts of trimeric (ExbB(3)), dimeric (ExbB(2)),
      and monomeric (ExbB(1)) oligomers. Under the same conditions ExbB-ExbD formed a
      subcomplex consisting of ExbB(6)ExbD(1), with a minor amount of ExbB(5)ExbD(1).
      At higher desorption laser intensities, ExbB(1) and ExbD(1) and traces of
      ExbB(3)ExbD(1), ExbB(2)ExbD(1), ExbB(1)ExbD(1), ExbB(3), and ExbB(2) were
      observed. Since the ExbB(6) complex and the ExbB(6)ExbD(1) complex remained
      stable during solubilization and subsequent chromatographic purification on
      nickel-nitrilotriacetate agarose, Strep-Tactin, and Superdex 200, and during
      native blue gel electrophoresis, we concluded that ExbB(6) and ExbB(6)ExbD(1) are
      subcomplexes on which the final complex including TonB is assembled.

PMID- 21905678
TI  - Dielectric and thermal effects on the optical properties of natural dyes: a case
      study on solvated cyanin.
AB  - The optical properties of the flavylium state of the cyanin dye are simulated
      numerically by combining Car-Parrinello molecular dynamics and linear-response
      time-dependent density functional theory calculations. The spectrum of the dye
      calculated in the gas phase is characterized by two peaks in the yellow and in
      the blue (green and violet), using a GGA-PBE (hybrid-B3LYP) DFT functional, which
      would bring about a greenish (bright orange) color incompatible with the dark
      purple hue observed in nature. Describing the effect of the water solvent through
      a polarizable continuum model does not modify qualitatively the resulting
      picture. An explicit simulation of both solvent and thermal effects using ab
      initio molecular dynamics results instead in a spectrum that is compatible with
      the observed coloration. This result is analyzed in terms of the spectroscopic
      effects of the molecular distortions induced by thermal fluctuations.

PMID- 21905679
TI  - Macroporous polymers obtained in highly concentrated emulsions stabilized solely
      with magnetic nanoparticles.
AB  - Magnetic macroporous polymers have been successfully prepared using Pickering
      high internal phase ratio emulsions (HIPEs) as templates. To stabilize the HIPEs,
      two types of oleic acid-modified iron oxide nanoparticles (NPs) were used as
      emulsifiers. The results revealed that partially hydrophobic NPs could stabilize
      W/O HIPEs with an internal phase above 90%. Depending upon the oleic acid
      content, the nanoparticles showed either an arrangement at the oil-water
      interface or a partial dispersion into the oil phase. Such different abilities to
      migrate to the interface had significant effects on the maximum internal phase
      fraction achievable and the droplet size distribution of the emulsions. Highly
      macroporous composite polymers were obtained by polymerization in the external
      phase of these emulsions. The density, porosity, pore morphology and magnetic
      properties were characterized as a function of the oleic acid content,
      concentration of NPs, and internal phase volume of the initial HIPEs. SEM imaging
      indicated that a close-cell structure was obtained. Furthermore, the composite
      materials showed superparamagnetic behavior and a relatively high magnetic
      moment.

PMID- 21905680
TI  - Deconstruction of the alpha4beta2 nicotinic acetylcholine receptor positive
      allosteric modulator desformylflustrabromine.
AB  - Desformylflustrabromine (dFBr; 1), perhaps the first selective positive
      allosteric modulator of alpha4beta2 neuronal nicotinic acetylcholine (nACh)
      receptors, was deconstructed to determine which structural features contribute to
      its actions on receptors expressed in  Xenopus  ooycytes using two-electrode
      voltage clamp techniques. Although the intact structure of 1 was found to be
      optimal, several deconstructed analogs retained activity. Neither the 6-bromo
      substituent nor the entire 2-position chain is required for activity. In
      particular, reduction of the olefinic side chain of 1, as seen with 6, not only
      resulted in retention of activity/potency but in enhanced selectivity for
      alpha4beta2 versus alpha7 nACh receptors. Pharmacophoric features for the
      allosteric modulation of alpha4beta2 nACh receptors by 1 were identified.

PMID- 21905681
TI  - Fluorescent properties and conformational preferences of C-linked phenolic-DNA
      adducts.
AB  - Phenolic toxins and mutagenic diazoquinones generate C-linked adducts at the C8
      site of 2'-deoxyguanosine (dG) through the intermediacy of radical species. We
      have previously reported the site-specific incorporation of these adducts into
      oligonucleotides using a postsynthetic palladium-catalyzed cross-coupling
      strategy [Omumi (2011 ) J. Am. Chem. Soc. 133 , 42 - 50 ]. We report here the
      structural impact of these lesions within two decanucleotide sequences containing
      either 5'- and 3'-flanking pyrimidines or purines. In the complementary strands,
      the base opposite (N) the C-linked adduct was varied to determine the possibility
      of mismatch stabilization by the modified nucleobases. The resulting adducted
      duplex structures were characterized using UV thermal denaturation studies,
      circular dichroism, fluorescence spectroscopy, and molecular dynamics (MD)
      simulations. The experimental data showed the C-linked adducts to destabilize the
      duplex when base paired with its normal partner C but to increase duplex
      stability within a G:G mismatch. The stabilization within the G:G mismatch was
      sequence dependent, with flanking purine bases playing a key role in the
      stabilizing influence of the adduct. MD simulations showed no large structural
      changes to the B form double helix, regardless of the (anti/syn) adduct
      preference. Consideration of H-bonding and stacking interactions derived from the
      MD simulations together with the thermal melting data and changes in fluorescent
      emission of the adducts upon hybridization to the complementary strands implied
      that the C-linked phenolic adducts preferentially adopt the syn-conformation
      within both duplexes regardless of the opposite base N. Given that biological
      outcome in terms of mutagenicity appears to be strongly correlated to the
      conformational preference of the corresponding N-linked C8-dG adducts, the
      potential biological implications of phenolic C-linked adducts are discussed.

PMID- 21905682
TI  - Enantioselective synthesis of dihydropyridinones via NHC-catalyzed aza-Claisen
      reaction.
AB  - N-Heterocyclic carbene catalyzed aza-Claisen annulations of enals or their alpha'
      hydroxyenone surrogates with vinylogous amides afford dihydropyridinones. The
      reaction proceeds with a broad range of substrates, and no nitrogen protecting
      group is required.

PMID- 21905683
TI  - Spectral properties of multiply charged semiconductor quantum dots.
AB  - Spectrally resolved fluorescence imaging of single CdSe/ZnS quantum dots (QDs),
      charged by electrospray deposition under negative bias has revealed a surprising
      net blue shift (~60 meV peak-to-peak) in the distribution of center frequencies
      in QD band-edge luminescence. Electrostatic force microscopy (EFM) on the
      electrospray QD samples showed a subpopulation of charged QDs with 4.7 +/- 0.7
      excess electrons, as well as a significant fraction of uncharged QDs as evidenced
      by the distinct cantilever response under bias. We show that the blue-shifted
      peak recombination energy can be understood as a first-order electronic
      perturbation that affects the band-edge electron- and hole-states differently.
      These studies provide new insight into the role of electronic perturbations of QD
      luminescence by excess charges.

PMID- 21905684
TI  - In situ hydrodynamic lateral force calibration of AFM colloidal probes.
AB  - Lateral force microscopy (LFM) is an application of atomic force microscopy (AFM)
      to sense lateral forces applied to the AFM probe tip. Recent advances in tissue
      engineering and functional biomaterials have shown a need for the surface
      characterization of their material and biochemical properties under the
      application of lateral forces. LFM equipped with colloidal probes of well-defined
      tip geometries has been a natural fit to address these needs but has remained
      limited to provide primarily qualitative results. For quantitative measurements,
      LFM requires the successful determination of the lateral force or torque
      conversion factor of the probe. Usually, force calibration results obtained in
      air are used for force measurements in liquids, but refractive index differences
      between air and liquids induce changes in the conversion factor. Furthermore, in
      the case of biochemically functionalized tips, damage can occur during
      calibration because tip-surface contact is inevitable in most calibration
      methods. Therefore, a nondestructive in situ lateral force calibration is
      desirable for LFM applications in liquids. Here we present an in situ
      hydrodynamic lateral force calibration method for AFM colloidal probes. In this
      method, the laterally scanned substrate surface generated a creeping Couette
      flow, which deformed the probe under torsion. The spherical geometry of the tip
      enabled the calculation of tip drag forces, and the lateral torque conversion
      factor was calibrated from the lateral voltage change and estimated torque.
      Comparisons with lateral force calibrations performed in air show that the
      hydrodynamic lateral force calibration method enables quantitative lateral force
      measurements in liquid using colloidal probes.

PMID- 21905685
TI  - Regional characterization of freshwater Use in LCA: modeling direct impacts on
      human health.
AB  - Life cycle assessment (LCA) is a methodology that quantifies potential
      environmental impacts for comparative purposes in a decision-making context.
      While potential environmental impacts from pollutant emissions into water are
      characterized in LCA, impacts from water unavailability are not yet fully
      quantified. Water use can make the resource unavailable to other users by
      displacement or quality degradation. A reduction in water availability to human
      users can potentially affect human health. If financial resources are available,
      there can be adaptations that may, in turn, shift the environmental burdens to
      other life cycle stages and impact categories. This paper proposes a model to
      evaluate these potential impacts in an LCA context. It considers the water that
      is withdrawn and released, its quality and scarcity in order to evaluate the loss
      of functionality associated with water uses. Regionalized results are presented
      for impacts on human health for two modeling approaches regarding affected users,
      including or not domestic uses, and expressed in disability-adjusted life years
      (DALY). A consumption and quality based scarcity indicator is also proposed as a
      midpoint. An illustrative example is presented for the production of corrugated
      board with different effluents, demonstrating the importance of considering
      quality, process effluents and the difference between the modeling approaches.

PMID- 21905686
TI  - Exploring the structure-solubility relationship of asphaltene models in toluene,
      heptane, and amphiphiles using a molecular dynamic atomistic methodology.
AB  - The solubility parameters, delta, of several asphaltene models were calculated by
      mean of an atomistic NPT ensemble. Continental and archipelago models were
      explored. A relationship between the solubility parameter and the molecule
      structure was determined. In general, increase of the fused-rings number forming
      the aromatic core and the numbers of heteroatoms such as oxygen, nitrogen, and
      sulfur produces an increase of the solubility parameter, while increases of the
      numbers and length of the aliphatic chains yield a systematic decrease of this
      parameter. Molecules with large total carbon atom number at the tails, n(c), and
      small aromatic ring number, n(r), exhibit the biggest values of delta, while
      molecules with small n(c) and large n(r) show the smallest delta values. A good
      polynomial correlation delta = 5.967(n(r)/n(c)) - 3.062(n(r)/n(c))(2) +
      0.507(n(r)/n(c))(3) + 16.593 with R(2) = 0.965 was found. The solubilities of the
      asphaltene models in toluene, heptane, and amphiphiles were studied using the
      Scatchard-Hildebrand and the Hansen sphere methodologies. Generally, there is a
      large affinity between the archipelago model and amphiphiles containing large
      aliphatic tails and no aromatic rings, while continental models show high
      affinity for amphiphiles containing an aromatic ring and small aliphatic chains.

PMID- 21905687
TI  - Nonviral pulmonary delivery of siRNA.
AB  - RNA interference (RNAi) is an important part of the cell's defenses against
      viruses and other foreign genes. Moreover, the biotechnological exploitation of
      RNAi offers therapeutic potential for a range of diseases for which drugs are
      currently unavailable. Unfortunately, the small interfering RNAs (siRNAs) that
      are central to RNAi in the cytoplasm are readily degradable by ubiquitous
      nucleases, are inefficiently targeted to desired organs and cell types, and are
      excreted quickly upon systemic injection. As a result, local administration
      techniques have been favored over the past few years, resulting in great success
      in the treatment of viral infections and other respiratory disorders.  Because
      there are several advantages of pulmonary delivery over systemic administration,
      two of the four siRNA drugs currently in phase II clinical trials are delivered
      intranasally or by inhalation. The air-blood barrier, however, has only limited
      permeability toward large, hydrophilic biopharmaceuticals such as nucleic acids;
      in addition, the lung imposes intrinsic hurdles to efficient siRNA delivery.
      Thus, appropriate formulations and delivery devices are very much needed.
      Although many different formulations have been optimized for in vitro siRNA
      delivery to lung cells, only a few have been reported successful in vivo. In this
      Account, we discuss both obstacles to pulmonary siRNA delivery and the success
      stories that have been achieved thus far.  The optimal pulmonary delivery vehicle
      should be neither cytotoxic nor immunogenic, should protect the payload from
      degradation by nucleases during the delivery process, and should mediate the
      intracellular uptake of siRNA. Further requirements include the improvement of
      the pharmacokinetics and lung distribution profiles of siRNA, the extension of
      lung retention times (through reduced recognition by macrophages), and the
      incorporation of reversible or stimuli-responsive binding of siRNA to allow for
      efficient release of the siRNAs at the target site. In addition, the ideal
      carrier would be biodegradable (to address difficulties with repeated
      administration for the treatment of chronic diseases) and would contain targeting
      moieties to enhance uptake by specific cell types. None of the currently
      available polymer- and lipid-based formulations meet every one of these
      requirements, but we introduce here several promising new approaches, including a
      biodegradable, nonimmunogenic polyester.  We also discuss imaging techniques for
      following the biodistribution according to the administration route. This
      tracking is crucial for better understanding the translocation and clearance of
      nanoformulated siRNA subsequent to pulmonary delivery.  In the literature, the
      success of pulmonary siRNA delivery is evaluated solely by relief from or
      prophylaxis against a disease; side effects are not studied in detail. It also
      remains unclear which cell types in the lung eventually take up siRNA. These are
      critical issues for the translational use of pulmonary siRNA formulations;
      accordingly, we present a flow cytometry technique that can be utilized to
      differentiate transfected cell populations in a mouse model that expresses
      transgenic enhanced green fluorescence protein (EGFP). This technique, in which
      different cell types are identified on the basis of their surface antigen
      expression, may eventually help in the development of safer carriers with
      minimized side effects in nontargeted tissues.

PMID- 21905688
TI  - Lamellar assembly of cadmium selenide nanoclusters into quantum belts.
AB  - Here, we elucidate a double-lamellar-template pathway for the formation of CdSe
      quantum belts. The lamellar templates form initially by dissolution of the CdX(2)
      precursors in the n-octylamine solvent. Exposure of the precursor templates to
      selenourea at room temperature ultimately affords (CdSe)(13) nanoclusters
      entrained within the double-lamellar templates. Upon heating, the nanoclusters
      are transformed to CdSe quantum belts having widths, lengths, and thicknesses
      that are predetermined by the dimensions within the templates. This template
      synthesis is responsible for the excellent optical properties exhibited by the
      quantum belts. We propose that the templated-growth pathway is responsible for
      the formation of the various flat, colloidal nanocrystals recently discovered,
      including nanoribbons, nanoplatelets, nanosheets, and nanodisks.

PMID- 21905689
TI  - Studies directed toward the elucidation of the pharmacophore of steroid-based
      Sonic Hedgehog signaling inhibitors.
AB  - Previous work from our laboratory has established that the readily available
      steroid-based analog 2 of cyclopamine 1 is, like 1, a highly potent inhibitor of
      Hedgehog signaling. The first structure-activity relationship studies on 2, i.e.,
      the synthesis and biological evaluation of both the C-17 epi analog 4 and the C-3
      deoxy analog 11, both of which are more potent than cyclopamine 1, are described.
      The implications of these results for the emerging pharmacophore of these Sonic
      Hedgehog signaling inhibitors are discussed.

PMID- 21905690
TI  - One-pot synthesis of uniform Fe3O4 nanospheres with carbon matrix support for
      improved lithium storage capabilities.
AB  - Poly(acrylic acid) (PAA)-entangled Fe(3)O(4) nanospheres are synthesized via a
      facile solvothermal method. In this system, ethylenediamine plays a very
      important role to control the uniformity of the nanospheres, and the PAA
      molecules serve as the carbon source that transforms into a carbon matrix after
      the heat treatment under an inert atmosphere. These uniform Fe(3)O(4) nanospheres
      with carbon matrix support manifest greatly enhanced lithium storage properties
      over prolonged cycling, with a reversible capacity of 712 mA h g(-1) retained
      after 60 charge/discharge cycles. However, the carbon-free counterpart can only
      deliver a much lower capacity of 328 mA h g(-1).

PMID- 21905691
TI  - Polymer-coated NaYF4:Yb3+, Er3+ upconversion nanoparticles for charge-dependent
      cellular imaging.
AB  - Lanthanide-doped upconversion nanoparticles (UCNPs) are considered promising
      novel near-infrared (NIR) bioimaging agents with the characteristics of high
      contrast and high penetration depth. However, the interactions between charged
      UCNPs and mammalian cells have not been thoroughly studied, and the corresponding
      intracellular uptake pathways remain unclear. Herein, our research work involved
      the use of a hydrothermal method to synthesize polyvinylpyrrolidone-coated UCNPs
      (UCNP-PVP), and then a ligand exchange reaction was performed on UCNP-PVP, with
      the help of polyethylenimine (PEI) and poly(acrylic acid) (PAA), to generate UCNP
      PEI and UCNP-PAA. These polymer-coated UCNPs demonstrated good dispersibility in
      aqueous medium, had the same elemental composition and crystal phase, shared
      similar TEM and dynamic light scattering (DLS) size distribution, and exhibited
      similar upconversion luminescence efficiency. However, the positively charged
      UCNP-PEI evinced greatly enhanced cellular uptake in comparison with its neutral
      or negative counterparts, as shown by multiphoton confocal microscopy and
      inductively coupled plasma mass spectrometry (ICP-MS) measurements. Meanwhile, we
      found that cationic UCNP-PEI can be effectively internalized mainly through the
      clathrin endocytic mechanism, as revealed by colocalization, chemical, and
      genetic inhibitor studies. This study elucidates the role of the surface polymer
      coatings in governing UCNP-cell interactions, and it is the first report on the
      endocytic mechanism of positively charged lanthanide-doped UCNPs. Furthermore,
      this study provides important guidance for the development of UCNPs as specific
      intracellular nanoprobes, allowing us to control the UCNP-cell interactions by
      tuning surface properties.

PMID- 21905692
TI  - Thin single-walled carbon nanotubes with narrow chirality distribution:
      constructive interplay of plasma and Gibbs-Thomson effects.
AB  - Multiscale, multiphase numerical modeling is used to explain the mechanisms of
      effective control of chirality distributions of single-walled carbon nanotubes in
      direct plasma growth and suggest effective approaches to further improvement. The
      model includes an unprecedented combination of the plasma sheath, ion/radical
      transport, species creation/loss, plasma-surface interaction, heat transfer,
      surface/bulk diffusion, graphene layer nucleation, and bending/lift-off modules.
      It is shown that the constructive interplay between the plasma and the Gibbs
      Thomson effect can lead to the effective nucleation and lift-off of small
      graphene layers on small metal catalyst nanoparticles. As a result, much thinner
      nanotubes with narrower chirality distributions can nucleate at much lower
      process temperatures and pressures compared to thermal CVD. This approach is
      validated by a host of experimental results, substantially reduces the amounts of
      energy and atomic matter required for the nanotube growth, and can be extended to
      other nanoscale structures and materials systems, thereby nearing the ultimate
      goal of energy- and matter-efficient nanotechnology.

PMID- 21905693
TI  - Molecular calipers control atomic separation at a metal surface.
AB  - If a molecule controls the length of some other moiety, it can be termed a
      "molecular caliper". Here we image individual molecular calipers of this type by
      scanning tunneling microscopy. These consist of linear polymers of p
      diiodobenzene, (pDIB)n, of varying length, 0.7-2.9 nm, physisorbed on Cu(110) at
      4.6 K. Through electron-induced reaction these chemically imprint their terminal
      I-atoms on the copper, 0.7 nm further apart than their initial separations. The
      physisorbed monomer or polymer, therefore, constitutes a molecular-caliper with
      variable terminal I..I separation. The localized nature of the I-atom reaction at
      the copper surface relative to the parent molecule, constitutes a novel finding
      reported here. It ensures that the separation of the I-atoms in the physisorbed
      molecular caliper correlates with their subsequent separation when chemisorbed at
      the surface.

PMID- 21905694
TI  - Greening coal: breakthroughs and challenges in carbon capture and storage.
AB  - Like it or not, coal is here to stay, for the next few decades at least.
      Continued use of coal in this age of growing greenhouse gas controls will require
      removing carbon dioxide from the coal waste stream. We already remove toxicants
      such as sulfur dioxide and mercury, and the removal of CO2 is the next step in
      reducing the environmental impacts of using coal as an energy source (i.e.,
      greening coal). This paper outlines some of the complexities encountered in
      capturing CO2 from coal, transporting it large distances through pipelines, and
      storing it safely underground.

PMID- 21905696
TI  - On the cavitation and pore blocking in cylindrical pores with simple
      connectivity.
AB  - We present a grand canonical Monte Carlo (GCMC) simulation of argon adsorption in
      connected cylindrical pores at 87.3 K. A number of pore models are constructed
      from various components: finite cylinder, finite cone, and flat surface. In the
      case of two cylinders of different sizes connected to each other with open ends,
      the adsorption isotherm can be described by a combination of two independent
      pores, the smaller of which is opened at both ends while the larger one is closed
      at one end. The adsorption isotherm depends on the relative size between the two
      sections of the connected pore. In the case of a cavity connected to the bulk
      surrounding gas via one or two narrower cylindrical necks, the phenomenon of
      either pore blocking or cavitation is observed, depending on the relative size
      between the neck and the cavity. If the neck size is smaller than a critical
      size, D(c), we observe cavitation, while pore blocking is observed when it is
      greater than D(c). This is due to the dominance of one of two mechanisms for
      removal of the adsorbates: either the receding of the menisci or the stretching
      of the fluid in the cavity. We also explore the effects of neck length and cavity
      length on the adsorption isotherm and conclude that while the neck length has a
      negligible effect on cavitation, it is of considerable importance when pore
      blocking occurs, because this process is controlled by the formation and movement
      of the meniscus in the pore neck. The effect of cavity length is found to be
      negligible in both cases.

PMID- 21905695
TI  - Relaxed but highly compact diansa metallacyclophanes.
AB  - A series of monoansa [MU-1,1'-PR-3,3'-Co(1,2-C(2)B(9)H(10))(2)](-) and diansa
      [8,8'-MU-(1'',2''-benzene)-MU-1,1'-PR-3,3'-Co(1,2-C(2)B(9)H(9))(2)](-) (R = Ph,
      (t)Bu) cobaltabisdicarbollidephanes have been synthesized, characterized and
      studied by NMR, MALDI-TOF-MS, UV-visible spectroscopy, cyclic voltammetry, and
      DFT calculations. Single crystal X-ray diffraction revealed a highly relaxed
      structure characterized by the title angle alpha of 3.8 degrees  ([7](-)), this
      being the smallest angle alpha for a metallacyclophane. In such compounds, the
      metal-to-phosphorus distance is less than the sum of their van der Waals radii.
      The availability of a phosphorus lone pair causes an electron delocalization
      through the metal, as shown by the abnormal (31)P NMR chemical shift. Remarkably,
      the combination of a phosphine donor and a phenyl acceptor moieties causes a
      synergistic effect that is observed through the different techniques used in this
      study. The importance of having an available lone pair is demonstrated by the
      oxidation of phosphorus with hydrogen peroxide, sulfur, and elemental black
      selenium to produce the corresponding P(V) compounds. When the electron lone pair
      is used to form the bond with the corresponding chalcogen atom, the communication
      between the donor and acceptor moieties on the diansa metallacyclophane is shut
      down.

PMID- 21905697
TI  - Analytic energy gradient in combined second-order Moller-Plesset perturbation
      theory and polarizable force field calculation.
AB  - Second-order Moller-Plesset perturbation theory (MP2) is used to describe
      electronic correlation on the basis of Hartree-Fock (HF) variational calculations
      that incorporate induced dipole polarizable force fields (i.e., QM/MMpol style HF
      and MP2). The Z-vector equations for regular closed shell and open shell MP2
      methods (RMP2, ZAPT2, and UMP2) are extended to include induced dipole
      contributions to determine the MP2 response density so that nuclear gradient and
      other properties can be efficiently evaluated. A better estimation of the induced
      dipole polarization energy can be obtained using the MP2 relaxed density.
      QM/MMpol style MP2 molecular dynamics simulations are performed for the ground
      state and first triplet state of acetone solvated by 1024 polarizable water
      molecules. A switching function is used to ensure energy conservation in QM/MM
      simulation under periodic boundary condition.

PMID- 21905698
TI  - Photophysics and photodynamics of 1'-hydroxy-2'-acetonaphthone (HAN) in micelles
      and nonionic surfactants forming vesicles: a comparative study of different
      microenvironments of surfactant assemblies.
AB  - The effect of different microenvironments inside various biomimicking
      supramolecular assemblies of ionic (SDS/CTAB) and nonionic (TX100) micelles and
      nonionic surfactants (Tween-80/PEG-6000) forming vesicles (niosome) on the
      photophysical and rotational dynamical properties of 1'-hydroxy-2'-acetonaphthone
      (HAN) have been studied using steady-state and time-resolved fluorescence
      spectroscopy. Enhanced fluorescence intensity with a significant blue shift and
      longer emission lifetime of the caged tautomers of HAN indicate modulation of
      photophysics of HAN upon encapsulation in both micellar assemblies and the
      niosome system. The binding constant and free energy change for the complexation
      of HAN with micelles and niosome demonstrate a comparative study on the binding
      efficiency of the different assemblies depending on the nature of
      microenvironments toward HAN. The enhancement in the steady-state anisotropy in
      niosome solutions compared with that in pure aqueous solution indicates that HAN
      is located inside the motionally restricted bilayer region of niosome. The
      fluorescence quenching experiment further reveals the probable location of HAN in
      micelles and niosome. In TX100 micelles, the obtained lifetime values are 417 ps
      and 1.63 ns for the caged tautomers, whereas in the comparatively more rigid and
      confined environment provided by niosome those values are 444 ps and 2.5 ns. The
      rotational relaxation time constants for the caged tautomers in niosome are also
      found to be higher than those in micelles. The observed difference in binding
      ability of the different assemblies is due to the difference in the extent of
      water penetration and different extent of rigidity around the fluorophore.

PMID- 21905699
TI  - Divergent regioselective synthesis of 2,5,6,7-tetrahydro-1H-1,4-diazepin-2-ones
      and 5H-1,4-benzodiazepines.
AB  - A novel and simple one-pot synthesis of 3-substituted 2,5,6,7-tetrahydro-1H-1,4
      diazepin-2-ones from 1,2-diaza-1,3-dienes (DDs) and N-unsubstituted aliphatic 1,3
      diamines is described. Here we also report a procedure to selectively obtain
      alkyl 5H-1,4-benzodiazepine-3-carboxylates from the DDs and 2-aminobenzylamine.
      Both processes occur by means of sequential 1,4-conjugated addition followed by
      regioselective 7-exo cyclization. The behavior of N-methyl- and N,N'-dimethyl-1,3
      diaminopropanes toward the DDs furnished pyrazol-3-ones and bis-alpha
      aminohydrazones, respectively.

PMID- 21905700
TI  - Direct interaction between an allosteric agonist pepducin and the chemokine
      receptor CXCR4.
AB  - Cell surface heptahelical G protein-coupled receptors (GPCRs) mediate critical
      cellular signaling pathways and are important pharmaceutical drug targets. (1) 
      In addition to traditional small-molecule approaches, lipopeptide-based GPCR
      derived pepducins have emerged as a new class of pharmaceutical agents. (2, 3) 
      To better understand how pepducins interact with targeted receptors, we developed
      a cell-based photo-cross-linking approach to study the interaction between the
      pepducin agonist ATI-2341 and its target receptor, chemokine C-X-C-type receptor
      4 (CXCR4). A pepducin analogue, ATI-2766, formed a specific UV-light-dependent
      cross-link to CXCR4 and to mutants with truncations of the N-terminus, the known
      chemokine docking site. These results demonstrate that CXCR4 is the direct
      binding target of ATI-2341 and suggest a new mechanism for allosteric modulation
      of GPCR activity. Adaptation and application of our findings should prove useful
      in further understanding pepducin modulation of GPCRs as well as enable new
      experimental approaches to better understand GPCR signal transduction.

PMID- 21905702
TI  - Novel mechanism for dehalogenation and glutathione conjugation of dihalogenated
      anilines in human liver microsomes: evidence for ipso glutathione addition.
AB  - The objective of the present study was to investigate the influence of halogen
      position on the formation of reactive metabolites from dihalogenated anilines.
      Herein we report on a proposed mechanism for dehalogenation and glutathione (GSH)
      conjugation of a series of ortho-, meta-, and para-dihalogenated anilines
      observed in human liver microsomes. Of particular interest were conjugates formed
      in which one of the halogens on the aniline was replaced by GSH. We present
      evidence that a (4-iminocyclohexa-2,5-dienylidene)halogenium reactive
      intermediate (QX) was formed after oxidation, followed by ipso addition of GSH at
      the imine moiety. The ipso GSH thiol attacks at the ortho-carbon and eventually
      leads to a loss of a halogen and GSH replacement. The initial step of GSH
      addition at the ipso position is also supported by density functional theory,
      which suggests that the ipso carbon of the chloro, bromo, and iodo (but not
      fluoro) containing 2-fluoro-4-haloanilines is the most positive carbon and that
      these molecules have the favorable highest occupied molecular orbital of the
      aniline and the lowest unoccupied orbital from GSH. The para-substituted halogen
      (chloro, bromo, or iodo but not fluoro) played a pivotal role in the formation of
      the QX, which required a delocalization of the positive charge on the para
      halogen after oxidation. This mechanism was supported by structure-metabolism
      relationship analysis of a series of dihalogenated and monohalogenated aniline
      analogues.

PMID- 21905701
TI  - Design of native-like proteins through an exposure-dependent environment
      potential.
AB  - We hypothesize that the degree of surface exposure of amino acid side chains
      within a globular, soluble protein has been optimized in evolution, not only to
      minimize the solvation free energy of the monomeric protein but also to prevent
      protein aggregation. This effect needs to be taken into account when engineering
      proteins de novo. We test this hypothesis through addition of a knowledge-based,
      exposure-dependent energy term to the RosettaDesign solvation potential
      [Lazaridis, T., and Karplus, M. (1999) Proteins 35, 133-152]. Correlation between
      amino acid type and surface exposure is determined from a representative set of
      experimental protein structures. The amino acid solvent accessible surface area
      (SASA) is estimated with a neighbor vector measure that increases in accuracy
      compared to the neighbor count measure while remaining pairwise decomposable
      [Durham, E., et al. (2009) J. Mol. Model. 15, 1093-1108]. Benchmarking of this
      potential in protein design displays a 3.2% improvement in the overall sequence
      recovery and an 8.5% improvement in recovery of amino acid types tolerated in
      evolution.

PMID- 21905703
TI  - Characterizing the adsorption of proteins on glass capillary surfaces using
      electrospray-differential mobility analysis.
AB  - We quantify the adsorption and desorption of a monoclonal immunoglobulin-G
      antibody, rituxamab (RmAb), on silica capillary surfaces using electrospray
      differential mobility analysis (ES-DMA). We first develop a theory to calculate
      coverages and desorption rate constants from the ES-DMA data for proteins
      adsorbing on glass capillaries used to electrospray protein solutions. This model
      is then used to study the adsorption of RmAb on a bare silica capillary surface.
      A concentration-independent coverage of ~4.0 mg/m(2) is found for RmAb
      concentrations ranging from 0.01 to 0.1 mg/mL. A study of RmAb adsorption to bare
      silica as a function of pH shows maximum adsorption at its isoelectric point (pI
      of pH 8.5) consistent with literature. The desorption rate constants are
      determined to be ~10(-5) s(-1), consistent with previously reported values, thus
      suggesting that shear forces in the capillary may not have a considerable effect
      on desorption. We anticipate that this study will allow ES-DMA to be used as a
      "label-free" tool to study adsorption of oligomeric and multicomponent protein
      systems onto fused silica as well as other surface modifications.

PMID- 21905704
TI  - Structural stability from solution to the gas phase: native solution structure of
      ubiquitin survives analysis in a solvent-free ion mobility-mass spectrometry
      environment.
AB  - The conformations of desolvated ubiquitin ions, lifted into the gas phase by
      electrospray ionization (ESI), were characterized by ion mobility spectrometry
      (IMS) and compared to the solution structures they originated from. The IMS
      instrument combining a two-meter helium drift tube with a quadrupole time-of
      flight mass spectrometer was built in-house. Solutions stabilizing the native
      state of ubiquitin yielded essentially one family of tightly folded desolvated
      ubiquitin structures with a cross section matching the size of the native state
      (1000 A(2)). Solutions favoring the A state yielded several well-defined families
      of significantly unfolded conformations (1800-2000 A(2)) matching in size
      conformations between the A state and a fully unfolded state. On the basis of
      these results and a wealth of data available in the literature, we conclude that
      the native state of ubiquitin is preserved in the transition from solution to the
      desolvated state during the ESI process and survives for >100 ms in a 294 K
      solvent-free environment. The A state, however, is charged more extensively than
      the native state during ESI and decays more rapidly following ESI. A state ions
      unfold on a time scale equal to or shorter than the experiment (<=50 ms) to more
      extended structures.

PMID- 21905705
TI  - Comparative properties of caveolar and noncaveolar preparations of kidney Na+/K+
      ATPase.
AB  - To evaluate previously proposed functions of renal caveolar Na(+)/K(+)-ATPase, we
      modified the standard procedures for the preparation of the purified membrane
      bound kidney enzyme, separated the caveolar and noncaveolar pools, and compared
      their properties. While the subunits of Na(+)/K(+)-ATPase (alpha,beta,gamma)
      constituted most of the protein content of the noncaveolar pool, the caveolar
      pool also contained caveolins and major caveolar proteins annexin-2 tetramer and
      E-cadherin. Ouabain-sensitive Na(+)/K(+)-ATPase activities of the two pools had
      similar properties and equal molar activities, indicating that the caveolar
      enzyme retains its ion transport function and does not contain nonpumping enzyme.
      As minor constituents, both caveolar and noncaveolar pools also contained Src,
      EGFR, PI3K, and several other proteins known to be involved in stimulous-induced
      signaling by Na(+)/K(+)-ATPase, indicating that signaling function is not limited
      to the caveolar pool. Endogenous Src was active in both pools but was not further
      activated by ouabain, calling into question direct interaction of Src with native
      Na(+)/K(+)-ATPase. Chemical cross-linking, co-immunoprecipitation, and
      immunodetection studies showed that in the caveolar pool, caveolin-1 oligomers,
      annexin-2 tetramers, and oligomers of the alpha,beta,gamma-protomers of
      Na(+)/K(+)-ATPase form a large multiprotein complex. In conjunction with known
      roles of E-cadherin and the beta-subunit of Na(+)/K(+)-ATPase in cell adhesion
      and noted intercellular beta,beta-contacts within the structure of Na(+)/K(+)
      ATPase, our findings suggest that interacting caveolar Na(+)/K(+)-ATPases located
      at renal adherens junctions maintain contact of two adjacent cells, conduct
      essential ion pumping, and are capable of locus-specific signaling in junctional
      cells.

PMID- 21905707
TI  - Ruthenium agostic (phosphinoaryl)borane complexes: multinuclear solid-state and
      solution NMR, X-ray, and DFT studies.
AB  - The reactivity of the (o-phosphinophenyl)(amino)borane compound
      HB(N(i)Pr(2))C(6)H(4)(o-PPh(2)) prepared from Li(C(6)H(4))PPh(2) and
      HBCl(N(i)Pr(2)) toward the bis(dihydrogen) complex RuH(2)(H(2))(2)(PCy(3))(2) (1)
      was studied by a combination of DFT, X-ray, and multinuclear NMR techniques
      including solid-state NMR, a technique rarely employed in organometallic
      chemistry. The study showed that the complex RuH(2){HB(N(i)Pr(2))C(6)H(4)(o
      PPh(2))}(PCy(3))(2) (3), isolated in excellent yield as yellow crystals and
      characterized by X-ray diffraction, led in solution to PCy(3) dissociation and
      formation of an unsaturated 16-electron complex RuH(2){HB(N(i)Pr(2))C(6)H(4)(o
      PPh(2))}(PCy(3)) (4), with a hydride trans to a vacant site. In both cases, the
      (phosphinoaryl)(amino)borane acts as a bifunctional ligand through the phosphine
      moiety and a Ru-H-B interaction, thus featuring an agostic interaction.

PMID- 21905706
TI  - Ookinete-interacting proteins on the microvillar surface are partitioned into
      detergent resistant membranes of Anopheles gambiae midguts.
AB  - Lipid raft microdomains, a component of detergent resistant membranes (DRMs), are
      routinely exploited by pathogens during host-cell entry. Multiple membrane
      surface proteins mediate Plasmodium ookinete invasion of the Anopheles midgut, a
      critical step in the parasite life cycle that is successfully targeted by
      transmission-blocking vaccines (TBV). Given that lipid rafts are a common feature
      of host-pathogen interactions, we hypothesized that they promote the partitioning
      of midgut surface proteins and thus facilitate ookinete invasion. In support of
      this hypothesis, we found that five of the characterized Anopheles TBV
      candidates, including the leading Anopheles TBV candidate, AgAPN1, are present in
      Anopheles gambiae DRMs. Therefore, to extend the repertoire of putative midgut
      ligands that can be targeted by TBVs, we analyzed midgut DRMs by tandem mass
      spectrometry. We identified 1452 proteins including several markers of DRMs.
      Since glycosylphosphotidyl inositol (GPI)-anchored proteins partition to DRMs, we
      characterized the GPI subproteome of An. gambiae midgut brush-border microvilli
      and found that 96.9% of the proteins identified in the GPI-anchored fractions
      were also present in DRMs. Our study vastly expands the number of candidate
      malarial TBV targets for subsequent analysis by the broader community and
      provides an inferred role for midgut plasmalemma microdomains in ookinete cell
      invasion.

PMID- 21905708
TI  - Development of flexible antimicrobial packaging materials against Campylobacter
      jejuni by incorporation of gallic acid into zein-based films.
AB  - In this study, antimicrobial films were developed against Campylobacter jejuni by
      incorporation of gallic acid (GA) into zein-based films. The zein and zein-wax
      composite films containing GA between 2.5 and 10 mg/cm(2) were effective on
      different C. jejuni strains in a concentration-dependent manner. Zein and zein
      wax composite films showed different release profiles in distilled water but
      quite similar release profiles at solid agar medium. Depending on incorporated GA
      concentration, 60-80% of GA released from the films, while the remaining GA was
      bound or trapped by film matrix. The GA at 2.5 and 5 mg/cm(2) caused a
      considerable increase in elongation (57-280%) of all zein films and eliminated
      their classical flexibility problems. The zein-wax composite films were less
      flexible than zein films, but the films showed similar tensile strengths and
      Young's modulus. Scanning electron microscopy indicated different morphologies of
      zein and zein-wax composite films. This study clearly showed the good potential
      of zein and GA to develop flexible antimicrobial films against C. jejuni.

PMID- 21905709
TI  - Liquid crystalline order and magnetocrystalline anisotropy in magnetically doped
      semiconducting ZnO nanowires.
AB  - Controlled alignment of nanomaterials over large length scales (>1 cm) presents a
      challenge in the utilization of low-cost solution processing techniques in
      emerging nanotechnologies. Here, we report on the lyotropic liquid crystalline
      behavior of transition-metal-doped zinc oxide nanowires and their facile
      alignment over large length scales under external fields. High aspect ratio Co-
      and Mn-doped ZnO nanowires were prepared by solvothermal synthesis with uniform
      incorporation of dopant ions into the ZnO wurtzite crystal lattice. The resulting
      nanowires exhibited characteristic paramagnetic behavior. Suspensions of surface
      functionalized doped nanowires spontaneously formed stable homogeneous nematic
      liquid crystalline phases in organic solvent above a critical concentration.
      Large-area uniaxially aligned thin films of doped nanowires were obtained from
      the lyotropic phase by applying mechanical shear and, in the case of Co-doped
      nanowires, magnetic fields. Application of shear produced thin films in which the
      nanowire long axes were aligned parallel to the flow direction. Conversely, the
      nanowires were found to orient perpendicular to the direction of the applied
      magnetic fields. This indicates that the doped ZnO possesses magnetocrystalline
      anisotropy sufficient in magnitude to overcome the parallel alignment which would
      be predicted based solely on the anisotropic demagnetizing field associated with
      the high aspect ratio of the nanowires. We use a combination of magnetic property
      measurements and basic magnetostatics to provide a lower-bound estimate for the
      magnetocrystalline anisotropy.

PMID- 21905710
TI  - Synthesis and characterization of a hydrogel with controllable electroosmosis: a
      potential brain tissue surrogate for electrokinetic transport.
AB  - Electroosmosis is the bulk fluid flow initiated by application of an electric
      field to an electrolyte solution in contact with immobile objects with a nonzero
      zeta-potential such as the surface of a porous medium. Electroosmosis may be used
      to assist analytical separations. Several gel-based systems with varying
      electroosmotic mobilities have been made in this context. A method was recently
      developed to determine the zeta-potential of organotypic hippocampal slice
      cultures (OHSC) as a representative model for normal brain tissue. The zeta
      potential of the tissue is significant. However, determining the role of the zeta
      potential in solute transport in tissue in an electric field is difficult because
      the tissue's zeta-potential cannot be altered. We hypothesized that mass
      transport properties, namely the zeta-potential and tortuosity, could be
      modulated by controlling the composition of a set of hydrogels. Thus,
      poly(acrylamide-co-acrylic acid) gels were prepared with three compositions (by
      monomer weight percent): acrylamide/acrylic acid 100/0, 90/10, and 75/25. The
      zeta-potentials of these gels at pH 7.4 are distinctly different, and in fact
      vary approximately linearly with the weight percent of acrylic acid. We
      discovered that the 25% acrylic acid gel is a respectable model for brain tissue,
      as its zeta-potential is comparable to the OHSC. This series of gels permits the
      experimental determination of the importance of electrokinetic properties in a
      particular experiment or protocol. Additionally, tortuosities were measured
      electrokinetically and by evaluating diffusion coefficients. Hydrogels with well
      defined zeta-potential and tortuosity may find utility in biomaterials and
      analytical separations, and as a surrogate model for OHSC and living biological
      tissues.

PMID- 21905711
TI  - NOM fractionation and fouling of low-pressure membranes in microgranular
      adsorptive filtration.
AB  - Membrane fouling by natural organic matter (NOM) was investigated in
      microgranular adsorptive filtration (MUGAF) systems, in which a thin layer of
      adsorbent is predeposited on low-pressure membranes. The adsorbents tested
      included heated aluminum oxide particles (HAOPs), ion exchange (IX) resin, and
      powdered activated carbon (PAC). Size exclusion chromatography (SEC) separated
      the NOM into four apparent MW fractions with significant UV254. HAOPs and the IX
      resin performed almost identically with respect to removal of these fractions,
      and differently from PAC. However, while HAOPs and PAC reduced fouling
      substantially, IX resin did not, indicating that fouling could not be attributed
      to the NOM fractions detected by SEC. Rather, the key foulants appear to comprise
      a very small fraction of the NOM with almost no UV254 absorbance. Alginate, a
      strongly fouling surrogate for natural polysaccharides, is adsorbed effectively
      by HAOPs, but not by IX resin or PAC, suggesting that polysaccharides sometimes
      play a key role in membrane fouling by NOM.

PMID- 21905712
TI  - Structure and bioactivity of thiosulfinates resulting from suppression of
      lachrymatory factor synthase in onion.
AB  - In normal onion (Allium cepa), trans-S-1-propenyl-L-cysteine sulfoxide is
      transformed via 1-propenesulfenic acid into propanethial S-oxide, a lachrymatory
      factor, through successive reactions catalyzed by alliinase and lachrymatory
      factor synthase (LFS). A recent report showed that suppression of the LFS
      activity caused a dramatic increase in thiosulfinates previously reported as
      "zwiebelane isomers". After purification by recycle high-performance liquid
      chromatography and subsequent analyses, we established the planar structure of
      the putative "zwiebelane isomers" as S-3,4-dimethyl-5-hydroxythiolane-2-yl 1
      propenethiosulfinate, in which two of the three molecules of 1-propenesulfenic
      acid involved in the formation gave the thiolane backbone, and the third molecule
      gave the thiosulfinate structure. Of at least three stereoisomers observed, one
      in the (2'R,3'R,4'R,5'R)-configuration was collected as an isolated fraction, and
      the other isomers were collected as a combined fraction because spontaneous
      tautomerization prevented further purification. Both fractions showed inhibitory
      activities against cyclooxygenase-1 and alpha-glucosidase in vitro.

PMID- 21905713
TI  - Characterization of graphene films and transistors grown on sapphire by metal
      free chemical vapor deposition.
AB  - We present a novel method for the direct metal-free growth of graphene on
      sapphire that yields high quality films comparable to that of graphene grown on
      SiC by sublimation. Graphene is synthesized on sapphire via the simple
      decomposition of methane at 1425-1600  degrees C. Film quality was found to be a
      strong function of growth temperature. The thickness, structure, interface
      characteristics, and electrical transport properties were characterized in order
      to understand the utility of this material for electronic devices. Graphene
      synthesized on sapphire is found to be strain relieved, with no evidence of an
      interfacial buffer layer. There is a strong correlation between the graphene
      structural quality and carrier mobility. Room temperature Hall effect mobility
      values were as high as 3000 cm(2)/(V s), while measurements at 2 K reached values
      of 10,500 cm(2)/(V s). These films also display evidence of the quantum Hall
      effect. Field effect transistors fabricated from this material had a typical
      current density of 200 mA/mm and transconductance of 40 mS/mm indicating that
      material performance may be comparable to graphene on SiC.

PMID- 21905714
TI  - Carryover of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS)
      from soil to plant and distribution to the different plant compartments studied
      in cultures of carrots (Daucus carota ssp. Sativus), potatoes (Solanum
      tuberosum), and cucumbers (Cucumis Sativus).
AB  - A vegetation study was carried out to investigate the carryover of
      Perfluorooctanoic Acid (PFOA) and Perfluorooctane Sulfonate (PFOS) from soil
      mixed with contaminated sewage sludge to potato, carrot, and cucumber plants.
      Analysis was done by liquid-extraction using acetonitrile with dispersive SPE
      cleanup and subsequent HPLC-MS/MS. In order to assess the transfer potential from
      soil, transfer factors (TF) were calculated for the different plant compartments:
      TF = [PFC](plant (wet substance))/[PFC](soil (dry weight)). The highest TF were
      found for the vegetative plant compartments with average values for PFOS below
      those for PFOA: cucumber, 0.17 (PFOS), 0.88 (PFOA); potato, 0.36 (PFOS), 0.40
      (PFOA); carrot, 0.38 (PFOS), 0.53 (PFOA). Transfer of PFOA and PFOS into potato
      peelings (average values of TF: PFOA 0.03, PFOS 0.04) exceeded the carryover to
      the peeled tubers (PFOA 0.01, PFOS < 0.01). In carrots, this difference did not
      occur (average values of TF: PFOA 0.04, PFOS 0.04). Transfer of PFOS into the
      unpeeled cucumbers was low and comparable to that of peeled potatoes (TF < 0.01).
      For PFOA, it was higher (TF: 0.03).

PMID- 21905715
TI  - Photocontrol over the disorder-to-order transition in thin films of polystyrene
      block-poly(methyl methacrylate) block copolymers containing photodimerizable
      anthracene functionality.
AB  - Reversible photocontrol over the ordering transition of block copolymers (BCPs)
      from a disordered state to an ordered state, namely the disorder-to-order
      transition (DOT), can be used to create long-range ordered nanostructures in self
      assembled BCPs over macroscopic distances by photocombing, similar to the classic
      zone refining used to produce highly pure, large single crystals. Here, we have
      designed and synthesized an anthracene-functionalized tri-BCP containing
      deuterated polystyrene (d(8)-PS) and poly(methyl methacrylate) (PMMA) blocks, as
      well as a short middle block of poly(2-hydroxyethyl methacrylates) (PHEMA) that
      is randomly functionalized by anthracene. This tri-BCP maintains the order-to
      disorder transition-type phase behavior of its parent d(8)-PS-b-PMMA di-BCPs.
      Under 365 nm UV irradiation, the junction between d(8)-PS and PMMA blocks is
      photocoupled through the anthracene photodimers, leading to a significant
      increase in the total molecular weight of the tri-BCP. As a consequence, when the
      tri-BCP is phase-mixed but close to the boundary of the ordering transition, it
      undergoes the DOT, as evidenced by small-angle neutron scattering and
      transmission electron microscopy. The tri-BCP could be reversibly brought through
      the DOT in thin films by taking advantage of photodimerization and thermal
      dissociation of anthracene. Currently, anthracene-functionalized d(8)-PS-b-PMMA
      BCP is one of the most promising candidates for the photocombing process to
      promote long-range laterally ordered nanostructures over macroscopic distances in
      a noninvasive manner.

PMID- 21905716
TI  - Antiproliferation effect and apoptosis mechanism of prostate cancer cell PC-3 by
      flavonoids and saponins prepared from Gynostemma pentaphyllum.
AB  - The objectives of this study were to investigate the antiproliferation and
      apoptosis mechanism of saponin and flavonoid fractions from Gynostemma
      pentaphyllum (Thunb.) Makino on prostate cancer cell PC-3. Both flavonoid and
      saponin fractions were isolated by a column chromatographic method with Cosmosil
      75C(18)-OPN as adsorbent and elution solvents of ethanol-water (30:70, v/v) for
      the former and 100% ethanol for the latter, followed by high-performance liquid
      chromatography-tandem mass spectrometry analysis. On the basis of the MTT assay,
      the saponin and flavonoid fraction were comparably effective in inhibiting the
      growth of PC-3 cells, with the IC(50) being 39.3 and 33.3 MUg/mL, respectively.
      Additionally, both fractions induced an arrest of PC-3 cell cycle at both S and
      G2/M phases, with both early and late apoptotic cell populations showing a dose
      dependent rise. The Western blot assay indicated that the incorporation of
      flavonoid or saponin fraction could modulate the expression of G2 and M
      checkpoint regulators, cyclins A and B, and the antiapoptotic proteins Bcl-2 and
      Bcl-xl and pro-apoptotic proteins Bad and Bax. The expression of the caspase-3
      and its activated downstream substrate effectors, DFF45 and poly (ADP-ribose)
      polymerase-1 (PARP-1), was also increased and followed a dose-dependent manner.
      All of these findings suggest that the apoptosis of PC-3 cells may proceed
      through the intrinsic mitochondria pathway.

PMID- 21905717
TI  - Exploration of transferability in multiscale coarse-grained peptide models.
AB  - Coarse-grained models can facilitate the efficient simulation of complex
      biological systems. In earlier studies the multiscale coarse-graining (MS-CG)
      method was employed to examine the folding landscape for two small peptides. In
      those studies, MS-CG force fields specific to each peptide were employed. We
      extend here the scope of that work with the goal of obtaining a transferable MS
      CG force field which can be used to simulate the folded conformations of peptides
      with disparate structural motifs. Information obtained via MS-CG modeling was
      used to understand the characteristics of CG interactions which govern their
      capacity to be transferred between different peptide systems. We find that polar
      CG groups are least transferable in general, with interactions between CG sites
      representing the CO and NH groups on the peptide backbone being particularly
      resistant to facile transfer. Our results additionally suggest that, while there
      are limitations to the approach, the MS-CG method may provide a systematic path
      toward obtaining rigorously defined CG interactions with at least some degree of
      transferability. These studies also indicate that it may be possible to enhance
      the transferability of the MS-CG approach by identifying novel ways to combine
      information from different MS-CG force fields.

PMID- 21905718
TI  - Immobilization of oligonucleotides onto zirconia-modified filter paper and
      specific molecular recognition.
AB  - A morphologically complex cellulosic substance (e.g., commercial filter paper)
      was employed as a substrate for DNA immobilization and successive recognition. A
      uniform ultrathin zirconia gel film was first deposited on each cellulose
      nanofiber in bulk filter paper by a facile sol-gel process. Relying on the large
      surface area of filter paper and the strong affinity of zirconia for the
      phosphate group, terminal-phosphate probe DNA was abundantly immobilized on the
      zirconia-modified filter paper so as to convert the composite to a biofunctional
      material for the sensitive and repetitive recognition of the corresponding
      complementary target DNA on the nanomolar level. By contrast, in spite of the
      viability of the immobilization of the probe DNA and the recognition of target
      DNA on the quartz plate, the amount of captured probe DNA or recognized target
      DNA on such a flat substrate was much less than that captured or recognized on
      filter paper, resulting in a relatively insensitive recognition event. Moreover,
      control experiments on bare filter paper (without a zirconia nanocoating)
      suggested that the zirconia gel film was essential to probe DNA immobilization
      and subsequent target DNA recognition.

PMID- 21905719
TI  - Catalytic degradation of the nerve agent VX by water-swelled polystyrene
      supported ammonium fluorides.
AB  - The catalytic degradation of the nerve agent VX (O-ethyl S-2
      (diisopropylamino)ethyl methylphosphonothioate) by water-swelled polymer
      supported ammonium fluorides is described. VX (0.06-0.53 mol/mol F(-)) is rapidly
      degraded (t(1/2) ~ 10-30 min) to form the "G-analogue" (O-ethyl
      methylphosphonofluoridate), which hydrolyzes (t(1/2) ~ 1-1.5 h) to the nontoxic
      EMPA (ethyl methylphosphonic acid). The toxic desethyl-VX is not formed. The
      catalytic effect of fluoride is maintained even when 6 equiv of VX are loaded. GB
      (O-isopropyl methylphosphonofluoridate) and desethyl-VX agents are also degraded
      under these conditions.

PMID- 21905720
TI  - Electrochemical DNA methylation detection for enzymatically digested CpG
      oligonucleotides.
AB  - We describe the electrochemical detection of DNA methylation through the direct
      oxidation of both 5-methylcytosine (mC) and cytosine (C) in 5'-CG-3' sequence
      (CpG) oligonucleotides using a sputtered nanocarbon film electrode after
      digesting a longer CpG oligonucleotide with endonuclease P1. Direct
      electrochemistry of the longer CpG oligonucleotides was insufficient for
      obtaining the oxidation currents of these bases because the CG rich sequence
      inhibited the direct oxidation of each base in the longer CpG oligonucleotides,
      owing to the conformational structure and its very low diffusion coefficient. To
      detect C methylation with better quantitativity and sensitivity in the relatively
      long CpG oligonucleotides, we successfully used an endonuclease P1 to digest the
      target CpG oligonucleotide and yield an identical mononucleotide 2'
      deoxyribonucleoside 5'-monophosphate (5'-dNMP). Compared with results obtained
      without P1 treatment, we achieved 4.4 times higher sensitivity and a wider
      concentration range for mC detection with a resolution capable of detecting a
      subtle methylated cytosine difference in the CpG oligonucleotides (60mer).

PMID- 21905721
TI  - Design, synthesis, and characterization of nucleic-acid-functionalized gold
      surfaces for biomarker detection.
AB  - Nucleic-acid-functionalized gold surfaces have been used extensively for the
      development of biological sensors. The development of an effective biomarker
      detection assay requires careful design, synthesis, and characterization of probe
      components. In this Feature Article, we describe fundamental probe development
      constraints and provide a critical appraisal of the current methodologies and
      applications in the field. We discuss critical issues and obstacles that impede
      the sensitivity and reliability of the sensors to underscore the challenges that
      must be met to advance the field of biomarker detection.

PMID- 21905722
TI  - Effect of tea catechins on regulation of antioxidant enzyme expression in H2O2
      induced skeletal muscle cells of goat in vitro.
AB  - Skeletal muscle cells (SMCs) of goats were stress induced with 1 mM H(2)O(2) in
      the absence or presence of 0.5, 5, and 50 MUg/mL tea catechins (TCs) incubation.
      Cells were harvested at 48 h postincubation with TCs to investigate the effects
      of TCs on cell proliferation, cell membrane integrity, antioxidant enzyme
      activities, and antioxidant enzyme genes and protein expression levels. Results
      showed that H(2)O(2) induction inhibited cell proliferation with or without TC
      incubation; moreover, the inhibition effect was enhanced in the presence of TCs
      (P < 0.001). H(2)O(2)-induced stress increased the lactate dehydrogenase (LDH)
      activity in the absence or presence of TC incubation, but concentrations of TCs,
      less than 5 MUg/mL, showed protective functions against LDH leakage than in other
      H(2)O(2)-induced treatments. The catalase (CAT) activity increased when SMCs were
      stress induced with H(2)O(2) in the absence or presence of TC incubation (P <
      0.001). H(2)O(2)-induced stress decreased CuZn superoxide dismutase (CuZn-SOD)
      and glutathione peroxidase (GPx) activities, whereas this effect was prevented by
      incubation with TCs in a concentration-dependent manner. H(2)O(2)-induced stress
      with or without TC incubation had significant effects on mRNA and protein
      expression levels of CAT, CuZn-SOD, and GPx (P < 0.001). CAT and CuZn-SOD mRNA
      expression levels were increased by different concentrations of TC incubation,
      and this tendency was basically consistent with corresponding protein expression
      levels. The GPx mRNA expression level increased with a low concentration of TCs
      but decreased with concentrations greater than 5 MUg/mL of TCs, whereas GPx
      protein expression in all TC-incubated groups was lower than in the control
      treatment. The current findings imply that TCs had an inhibitory effect on cell
      proliferation and enhanced damage to the cell membrane integrity, but TCs
      affected antioxidant status in SMCs by modulating antioxidant enzyme activities
      at mRNA and protein expression levels.

PMID- 21905723
TI  - Influence of foam structure on the release kinetics of volatiles from espresso
      coffee prior to consumption.
AB  - The relationship between the physical structure of espresso coffee foam, called
      crema, and the above-the-cup aroma release was studied. Espresso coffee samples
      were produced using the Nespresso extraction system. The samples were extracted
      with water with different levels of mineral content, which resulted in liquid
      phases with similar volatile profiles but foams with different structure
      properties. The structure parameters foam volume, foam drainage, and lamella film
      thickness at the foam surface were quantified using computer-assisted microscopic
      image analysis and a digital caliper. The above-the-cup volatile concentration
      was measured online by using PTR-MS and headspace sampling. A correlation study
      was done between crema structure parameters and above-the-cup volatile
      concentration. In the first 2.5 min after the start of the coffee extraction, the
      presence of foam induced an increase of concentration of selected volatile
      markers, independently if the crema was of high or low stability. At times longer
      than 2.5 min, the aroma marker concentration depends on both the stability of the
      crema and the volatility of the specific aroma compounds. Mechanisms of above-the
      cup volatile release involved gas bubble stability, evaporation, and diffusion.
      It was concluded that after the initial aroma burst (during the first 2-3 min
      after the beginning of extraction), for the present sample space a crema of high
      stability provides a stronger aroma barrier over several minutes.

PMID- 21905725
TI  - Purification and characterization of a novel extracellular tripeptidyl peptidase
      from Rhizopus oligosporus.
AB  - A novel extracellular tripeptidyl peptidase (TPP) was homogenously purified from
      the culture supernatant of  Rhizopus oligosporus  by sequential fast protein
      liquid chromatography. The purified enzyme was a 136.5 kDa dimer composed of
      identical subunits. The effects of inhibitors and metal ions indicated that TPP
      is a metallo- and serine protease. TPP was activated by divalent cations, such as
      Co(2+) and Mn(2+), and completely inhibited by Cu(2+). Enzyme activity was
      optimal at pH 7.0 and 45  degrees C with a specific activity of 281.9 units/mg
      for the substrate Ala-Ala-Phe-pNA. The purified enzyme catalyzed cleavage of
      various synthetic tripeptides but not when proline occupied the P1 position.
      Purified TPP cleaved the pentapeptide Ala-Ala-Phe-Tyr-Tyr and tripeptide Ala-Ala
      Phe, confirming the TPP activity of the enzyme.

PMID- 21905724
TI  - Designing electrochemical interfaces with functionalized magnetic nanoparticles
      and wrapped carbon nanotubes as platforms for the construction of high
      performance bienzyme biosensors.
AB  - The design of a novel biosensing electrode surface, combining the advantages of
      magnetic ferrite nanoparticles (MNPs) functionalized with glutaraldehyde (GA) and
      poly(diallyldimethylammonium chloride) (PDDA)-coated multiwalled carbon nanotubes
      (MWCNTs) as platforms for the construction of high-performance multienzyme
      biosensors, is reported in this work. Before the immobilization of enzymes, GA
      MNP/PDDA/MWCNT composites were prepared by wrapping of carboxylated MWCNTs with
      positively charged PDDA and interaction with GA-functionalized MNPs. The
      nanoconjugates were characterized by scanning electron microscopy (SEM) and
      electrochemistry. The electrode platform was used to construct a bienzyme
      biosensor for the determination of cholesterol, which implied coimmobilization of
      cholesterol oxidase (ChOx) and peroxidase (HRP) and the use of hydroquinone as
      redox mediator. Optimization of all variables involved in the preparation and
      analytical performance of the bienzyme electrode was accomplished. At an applied
      potential of -0.05 V, a linear calibration graph for cholesterol was obtained in
      the 0.01-0.95 mM concentration range. The detection limit (0.85 MUM), the
      apparent Michaelis-Menten constant (1.57 mM), the stability of the biosensor, and
      the calculated activation energy can be advantageously compared with the
      analytical characteristics of other CNT-based cholesterol biosensors reported in
      the literature. Analysis of human serum spiked with cholesterol at different
      concentration levels yielded recoveries between 100% and 103%

PMID- 21905726
TI  - Studies of liquid crystalline self-assembly of GdF3 nanoplates by in-plane, out
      of-plane SAXS.
AB  - Directed self-assembly of colloidal nanocrystals into ordered superlattices
      enables the preparation of novel metamaterials with diverse functionalities.
      Structural control and precise characterization of these superlattices allow the
      interactions between individual nanocrystal building blocks and the origin of
      their collective properties to be understood. Here, we report the directed liquid
      interfacial assembly of gadolinium trifluoride (GdF(3)) nanoplates into liquid
      crystalline assemblies displaying long-range orientational and positional order.
      The macroscopic orientation of superlattices is controlled by changing the
      subphases upon which liquid interfacial assembly occurs. The assembled structures
      are characterized by a combination of transmission electron microscopy (TEM) and
      small-angle X-ray scattering (SAXS) measurements performed on a laboratory
      diffractometer. By doping GdF(3) nanoplates with europium (Eu(3+)), luminescent
      phosphorescent superlattices with controlled structure are produced and enable
      detailed structural and optical characterization.

PMID- 21905727
TI  - Fabrication of ultrafine metal-oxide-decorated carbon nanofibers for DMMP sensor
      application.
AB  - Ultrafine metal-oxide-decorated hybrid carbon nanofibers (CNFs) were fabricated
      by a single-nozzle co-electrospinning process using a phase-separated mixed
      polymer composite solution and heat treatment. To decorate metal oxides on the
      CNF surface, core (PAN) and shell (PVP) structured nanofibers (NFs) were
      fabricated as starting materials. The core-shell NF structure was prepared by
      single-nozzle co-electrospinning because of the incompatibility of the two
      polymers. Ultrafine hybrid CNFs were then formed by decomposing the PVP phase,
      converting the metal precursors to metal oxide nanonodules, and transforming the
      PAN to CNFs of ca. 40 nm diameter during heat treatment. The decoration
      morphology of the metal oxide nanonodules could be controlled by precursor
      concentration in the PVP solution. These ultrafine hybrid CNFs were applied to a
      dimethyl methylphosphonate (DMMP) chemical sensor at room temperature with
      excellent sensitivity. The minimum detectable level (MDL) of hybrid CNFs was as
      low as 0.1 ppb, which is 10-100 times higher than for a chemical sensor based on
      carbon nanotubes. This is because the metal oxide nanonodules of hybrid CNFs
      increase the surface area and affinity to DMMP vapor. Our new synthetic
      methodology promises to be an effective approach to fabricating hybrid
      CNF/inorganic nanostructures for future sensing technologies.

PMID- 21905728
TI  - Morpholinecarbonyl-Rhodamine 110 based substrates for the determination of
      protease activity with accurate kinetic parameters.
AB  - Commonly used fluorogenic substrate analogues for the detection of protease
      activity contain two enzyme-cleavable bonds conjugated to the fluorophore.
      Enzymatic cleavage follows a two-step reaction with a monoamide intermediate.
      This intermediate shows fluorescence at the same wavelength as the final product
      complicating the kinetic analysis of fluorescence-based assays. Fluorogenic
      substrate analogues for alpha-chymotrypsin with one cleavable peptide bond have
      been prepared from morpholinecarbonyl-Rhodamine 110 (MC-Rh110). A comparison of
      their kinetic properties with the corresponding (peptide)(2)-Rh110 derivatives
      revealed that these frequently used double-substituted substrate analogues yield
      only apparent K(m) and k(cat) values that are quite different from the kinetic
      parameters obtained from the monosubstituted MC-Rh110 based substrate analogues.
      Although both the monoamide intermediate and MC-Rh110 are monosubstituted
      Rhodamine 110 derivatives, they show different spectroscopic properties. The data
      from the spectroscopic analysis clearly show that these properties are directly
      related to the electron structure of the fluorophore and not to the previously
      proposed equilibrium between the lactone form and the open ionic form of the
      fluorophore. This knowledge about the determinants of the spectroscopic
      properties of monosubstituted Rhodamine 110 introduces a way for a more
      systematic development of new fluorogenic protease substrate analogues.

PMID- 21905729
TI  - Effects of Ginkgo biloba constituents on fruit-infesting behavior of codling moth
      (Cydia pomonella) in apples.
AB  - Codling moth, Cydia pomonella (L.), is a cosmopolitan pest of apple, potentially
      causing severe damage to the fruit. Currently used methods of combating this
      insect do not warrant full success or are harmful to the environment. The use of
      plant-derived semiochemicals for manipulation with fruit-infesting behavior is
      one of the new avenues for controlling this pest. Here, we explore the potential
      of Ginkgo biloba and its synthetic metabolites for preventing apple feeding and
      infestation by neonate larvae of C. pomonella. Experiments with crude extracts
      indicated that deterrent constituents of ginkgo are present among alkylphenols,
      terpene trilactones, and flavonol glycosides. Further experiments with ginkgo
      synthetic metabolites of medical importance, ginkgolic acids, kaempferol,
      quercetin, isorhamnetin, ginkgolides, and bilobalide, indicated that three out of
      these chemicals have feeding deterrent properties. Ginkgolic acid 15:0 prevented
      fruit infestation at concentrations as low as 1 mg/mL, bilobalide had deterrent
      effects at 0.1 mg/mL and higher concentrations, and ginkgolide B at 10 mg/mL. On
      the other hand, kaempferol and quercetin promoted fruit infestation by codling
      moth neonates. Ginkgolic acids 13:0, 15:1, and 17:1, isorhamnetin, and
      ginkgolides A and C had no effects on fruit infestation-related behavior. Our
      research is the first report showing that ginkgo constituents influence fruit
      infestation behavior and have potential applications in fruit protection.

PMID- 21905730
TI  - Design, synthesis, and functionalization of dimeric peptides targeting chemokine
      receptor CXCR4.
AB  - The chemokine receptor CXCR4 is a critical regulator of inflammation and immune
      surveillance, and it is specifically implicated in cancer metastasis and HIV-1
      infection. On the basis of the observation that several of the known antagonists
      remarkably share a C(2) symmetry element, we constructed symmetric dimers with
      excellent antagonistic activity using a derivative of a cyclic pentapeptide as
      monomer. To optimize the binding affinity, we investigated the influence of the
      distance between the monomers and the pharmacophoric sites in the synthesized
      constructs. The affinity studies in combination with docking computations support
      a two-site binding model. In a final step, 1,4,7,10-tetraazacyclododecane
      1,4,7,10-tetraacetic acid (DOTA) was introduced as chelator for (radio-)metals,
      thus allowing to exploit these compounds as a new group of CXCR4-binding peptidic
      probes for molecular imaging and endoradiotherapeutic purposes. Both the DOTA
      conjugates and some of their corresponding metal complexes retain good CXCR4
      affinity, and one (68)Ga labeled compound was studied as PET tracer.

PMID- 21905731
TI  - Atomic alignment effect in the dissociative energy transfer reaction of metal
      carbonyls (Fe(CO)5, Ni(CO)4) with oriented Ar (3P2, M(J) = 2).
AB  - The atomic alignment effect has been studied for the dissociative energy transfer
      reaction of metal carbonyls (Fe(CO)(5), Ni(CO)(4)) with the oriented Ar ((3)P(2),
      M(J) = 2). The emission intensity from the excited metal products (Fe*, Ni*) has
      been measured as a function of the atomic alignment in the collision frame. The
      selectivity of the atomic orbital alignment of Ar ((3)P(2), M(J) = 2) (rank 2
      moment, a(2)) is found to be opposite for the two reaction systems; the Fe(CO)(5)
      reaction is favorable at the Pi configuration (positive a(2)), while the
      Ni(CO)(4) reaction is favorable at the Sigma configuration (negative a(2)).
      Moreover, a significant spin alignment effect (rank 4 moment, a(4)) is recognized
      only in the Ni(CO)(4) reaction. The atomic alignment effect turns out to be
      essentially different between the two reaction systems; the Fe(CO)(5) reaction is
      controlled by the configuration of the half-filled 3p atomic orbital of Ar
      ((3)P(2)) in the collision frame (L dependence), whereas the Ni(CO)(4) reaction
      is controlled by the configuration of the total angular moment J (including spin)
      of Ar ((3)P(2)) in the collision frame (J dependence). As the origin of J
      dependence observed only in the Ni(CO)(4) reaction, the correlation (and/or the
      interference) between two electron exchange processes via the electron
      rearrangements is proposed.

PMID- 21905732
TI  - In situ characterization of alloy catalysts for low-temperature graphene growth.
AB  - Low-temperature (~450  degrees C), scalable chemical vapor deposition of
      predominantly monolayer (74%) graphene films with an average D/G peak ratio of
      0.24 and domain sizes in excess of 220 MUm(2) is demonstrated via the design of
      alloy catalysts. The admixture of Au to polycrystalline Ni allows a controlled
      decrease in graphene nucleation density, highlighting the role of step edges. In
      situ, time-, and depth-resolved X-ray photoelectron spectroscopy and X-ray
      diffraction reveal the role of subsurface C species and allow a coherent model
      for graphene formation to be devised.

PMID- 21905733
TI  - Quantification of phenolic compounds during red winemaking using FT-MIR
      spectroscopy and PLS-regression.
AB  - We present a rapid method to quantify phenolic compounds all during the red
      winemaking process using Fourier transform mid-infrared (FT-MIR) spectroscopy and
      chemometrics. To get the reference values, we used the usual UV-vis spectroscopy
      methods, and the compounds studied were evaluated as total phenolic compounds
      (TPC), total anthocyanins (TA), and condensed tannins (CT). Sampling from five
      different grape varieties (Merlot, Tempranillo, Syrah, Carinena, and Cabernet
      sauvignon), harvested at different ripening states, and monitored over 10 days of
      vinification produced a total of 600 spectra. These were used to build and
      validate four different predictive models by partial least-squares (PLS)
      regression. The spectral regions selected for each model were between 979 and
      2989 cm(-1), and when selecting the most suitable one in each case, good values
      of performance parameters were obtained (R2(val) > 0.95 and RPD > 4.0 for TPC;
      R2(val) > 0.90 and RPD > 3.0 for TA; R2(val) < 0.8 and RPD < 3.0 for CT).
      Furthermore, also more specific PLS regression models for each phenolic parameter
      and each grape variety were developed using different regions with results
      similar to those obtained when dealing with all of the grape varieties. It is
      concluded that FT-MIR spectroscopy together with multivariate calibration could
      be a rapid and valuable tool for wineries to carry out the monitoring of phenolic
      compound extraction during winemaking.

PMID- 21905734
TI  - Comparison of the absorption, emission, and resonance Raman spectra of 7
      hydroxyquinoline and 8-bromo-7-hydroxyquinoline caged acetate.
AB  - To better understand the deprotection reaction of the new promising phototrigger
      compound BHQ-OAc (8-bromo-7-hydroxyquinoline acetate), we present a detailed
      comparison of the UV-vis absorption, resonance Raman, and fluorescence spectra of
      BHQ-OAc with its parent compound 7-hydroxyquinoline in different solvents. The
      steady-state absorption and resonance Raman spectra provide fundamental
      information about the structure, properties, and population distribution of the
      different prototropic forms present under the different solvent conditions
      examined. The species present in the excited states that emit strongly were
      detected by fluorescence spectra. It is shown that the ground-state
      tautomerization process of BHQ-OAc is disfavored compared with that of 7-HQ in
      aqueous solutions. The observation of the tautomeric form of BHQ-OAc in neutral
      aqueous solutions demonstrates the occurrence of the excited-state proton
      transfer process, which would be a competing process for the deprotection
      reaction of BHQ-OAc in aqueous solutions.

PMID- 21905735
TI  - Identification and quantification of metallo-chlorophyll complexes in bright
      green table olives by high-performance liquid chromatrography-mass spectrometry
      quadrupole/time-of-flight.
AB  - Five different samples of table olives, two regular Spanish table olives and
      three "bright green table olives", have been analyzed by HPLC-MS/MS to determine
      their pigment profile. Typical pigment profiles of almost all table olives show
      primarily chlorophyll derivatives lacking metals (e.g., pheophytin a/b and 15(2)
      Me-phytol-chlorin e(6)). Bright green table olives have a unique profile
      including metallo-chlorophyll complexes (Cu-15(2)-Me-phytol-chlorin e(6) with 26
      48% and Cu-pheophytin a with 3-18%) as their major pigments. New tentative
      structures have been identified by MS such as 15(2)-Me-phytol-rhodin g(7), 15(2)
      Me-phytol-chlorin e(6), 15(2)-Me-phytol-isochlorin e(4), Cu-15(2)-Me-phytol
      rhodin g(7), Cu-15(2)-Me-phytol-chlorin e(6), and Cu-15(2)-Me-phytol-isochlorin
      e(4), and new MS/MS fragmentation patterns are reported for Cu-15(2)-Me-phytol
      rhodin g(7), Cu-15(2)-Me-phytol-chlorin e(6), Cu-pheophytin b, Cu-pheophytin a,
      Cu-pyropheophytin b, and Cu-pyropheophytin a. The presence of metallo-chlorophyll
      derivatives is responsible for the intense color of bright green table olives,
      but these metallo-chlorophyll complexes may be regarded as a "green staining"
      defect that is unacceptable to consumers.

PMID- 21905736
TI  - Characterization of phytochemicals and antioxidant activities of a purple tomato
      (Solanum lycopersicum L.).
AB  - A newly developed nongenetically modified purple tomato V118 was investigated for
      its phytochemical compositions and antioxidant activities. A highly efficient and
      sensitive UPLC method was developed for both the phenolics and carotenoids, which
      showed that in addition to the phytochemicals commonly known for tomatoes, V118
      had a unique composition of anthocyanins. The total carotenoid content of V118
      was 234.78 MUg/g dry weight (DW), and the total phenolic content was 659.11 mg
      GAE/100 g DW. The antioxidant activities of the lipophilic extract as measured by
      the PCL and ORAC-L assays were 30.11 MUmol TE/g DW and 11.97 MUmol TE/g DW,
      respectively, while the hydrophilic extracts as determined by the ORAC-H and FRAP
      assays were 323.23 MUmol TE/g DW and 54.95 MUmol AAE/g DW, respectively. The LC
      MS study showed three major anthocyanins, which were mainly acylglycosides of
      petunidin and malvidin. This study showed that purple tomatoes such as V118
      possess additional phytochemicals like anthocyanins, which can potentially have
      added health benefits.

PMID- 21905737
TI  - Photochemistry of Acetabularia rhodopsin II from a marine plant, Acetabularia
      acetabulum.
AB  - Acetabularia rhodopsins are the first microbial rhodopsins discovered in a marine
      plant organism, Acetabularia acetabulum. Previously, we expressed Acetabularia
      rhodopsin II (ARII) by a cell-free system from one of two opsin genes in A.
      acetabulum cDNA and showed that ARII is a light-driven proton pump [Wada, T., et
      al. (2011) J. Mol. Biol. 411, 986-998]. In this study, the photochemistry of ARII
      was examined using the flash-photolysis technique, and data were analyzed using a
      sequential irreversible model. Five photochemically defined intermediates (P(i))
      were sufficient to simulate the data. Noticeably, both P(3) and P(4) contain an
      equilibrium mixture of M, N, and O. Using a transparent indium tin oxide
      electrode, the photoinduced proton transfer was measured over a wide pH range.
      Analysis of the pH-dependent proton transfer allowed estimation of the pK(a)
      values of some amino acid residues. The estimated values were 2.6, 5.9 (or 6.3),
      8.4, 9.3, 10.5, and 11.3. These values were assigned as the pK(a) of Asp81
      (Asp85(BR)) in the dark, Asp92 (Asp96(BR)) at N, Glu199 (Glu204(BR)) at M, Glu199
      in the dark, an undetermined proton-releasing residue at the release, and the pH
      to start denaturation, respectively. Following this analysis, the proton transfer
      of ARII is discussed.

PMID- 21905738
TI  - Synthesis of new 3,20-bispolyaminosteroid squalamine analogues and evaluation of
      their antimicrobial activities.
AB  - 3,20-Amino- and polyaminosteroid analogues of squalamine and trodusquemine were
      synthesized involving a stereoselective titanium reductive amination reaction in
      high chemical yields in numerous cases. These derivatives were evaluated for
      their in vitro antimicrobial properties against references and clinical bacterial
      strains exhibiting minimum inhibitory concentrations of 2.5-40 MUg/mL. The
      mechanism of action of these derivatives was determined using bioluminescence for
      ATP efflux measurements and fluorescence methods for membrane depolarization
      assays.

PMID- 21905740
TI  - Compact antenna for efficient and unidirectional launching and decoupling of
      surface plasmons.
AB  - Controlling the launching efficiencies and the directionality of surface plasmon
      polaritons (SPPs) and their decoupling to freely propagating light is a major
      goal for the development of plasmonic devices and systems. Here, we report on the
      design and experimental observation of a highly efficient unidirectional surface
      plasmon launcher composed of eleven subwavelength grooves, each with a distinct
      depth and width. Our observations show that, under normal illumination by a
      focused Gaussian beam, unidirectional SPP launching with an efficiency of at
      least 52% is achieved experimentally with a compact device of total length
      smaller than 8 MUm. Reciprocally, we report that the same device can efficiently
      convert SPPs into a highly directive light beam emanating perpendicularly to the
      sample.

PMID- 21905739
TI  - Design, synthesis, and biological evaluation of chromone-based p38 MAP kinase
      inhibitors.
AB  - 3-(4-Fluorophenyl)-2-(4-pyridyl)chromone derivatives were synthesized and
      evaluated as p38 MAP kinase inhibitors. Introduction of an amino group in the 2
      position of the pyridyl moiety gave p38alpha inhibitors with IC(50) in the low
      nanomolar range (e.g., IC(50) = 17 nm). The inhibitors showed excellent
      selectivity profiles when tested on a panel of 62 kinases, as well as efficient
      inhibition of p38 signaling in human breast cancer cells.

PMID- 21905741
TI  - Tuning G-quadruplex vs double-stranded DNA recognition in regioisomeric lysyl
      peptidyl-anthraquinone conjugates.
AB  - Anthraquinone is a versatile scaffold to provide effective DNA binders. This
      planar system can be easily conjugated to protonable side chains: the nature of
      the lateral groups and their positions around the tricyclic moiety largely affect
      the DNA recognition process in terms of binding affinity and mode, as well as
      sequence and structure of the target nucleic acid. Starting from an
      anthracenedione system symmetrically functionalized with N-terminal lysyl
      residues, we incremented the length of side chains by introducing a Gly, Ala, or
      Phe spacer, characterized by different flexibility, lipophilicity, and bulkiness.
      Moreover, 2,6, 2,7, 1,8, and 1,5 regioisomers were examined to yield a small
      bis(lysyl-peptidyl) anthracenedione library. By merging spectroscopic, enzymatic,
      and cellular results, we showed that the proper combination of a basic aminoacid
      (Lys) with a more hydrophobic residue (Phe) can provide selective G-quadruplex
      recognition, in particular when side chains are located at positions 2,6 or 2,7.
      In fact, while these derivatives effectively bind G-quadruplex structures, they
      behave at the same time as rather poor double-stranded DNA intercalators. As a
      result, the Lys-Phe substituted anthraquinones are poorly cytotoxic but still
      able to promote a senescence mechanism in cancer cells. This combination of
      chemical and biological properties foresees potentially valuable applications in
      anticancer medicinal chemistry.

PMID- 21905742
TI  - Conjugation of type I antifreeze protein to polyallylamine increases thermal
      hysteresis activity.
AB  - Antifreeze proteins (AFPs) are ice binding proteins found in some plants,
      insects, and Antarctic fish allowing them to survive at subzero temperatures by
      inhibiting ice crystal growth. The interaction of AFPs with ice crystals results
      in a difference between the freezing and melting temperatures, termed thermal
      hysteresis, which is the most common measure of AFP activity. Creating antifreeze
      protein constructs that reduce the concentration of protein needed to observe
      thermal hysteresis activities would be beneficial for diverse applications
      including cold storage of cells or tissues, ice slurries used in refrigeration
      systems, and food storage. We demonstrate that conjugating multiple type I AFPs
      to a polyallylamine chain increases thermal hysteresis activity compared to the
      original protein. The reaction product is approximately twice as active when
      compared to the same concentration of free proteins, yielding 0.5  degrees C
      thermal hysteresis activity at 0.3 mM protein concentration. More impressively,
      the amount of protein required to achieve a thermal hysteresis of 0.3  degrees C
      is about 100 times lower when conjugated to the polymer (3 MUM) compared to free
      protein (300 MUM). Ice crystal morphologies observed in the presence of the
      reaction product are comparable to those of the protein used in the conjugation
      reaction.

PMID- 21905745
TI  - Analysis and status of post-combustion carbon dioxide capture technologies.
AB  - The Electric Power Research Institute (EPRI) undertook a multiyear effort to
      understand the landscape of postcombustion CO2 capture technologies globally. In
      this paper we discuss several central issues facing CO2 capture involving scale,
      energy, and overall status of development. We argue that the scale of CO2
      emissions is sufficiently large to place inherent limits on the types of capture
      processes that could be deployed broadly. We also discuss the minimum energy
      usage in terms of a parasitic load on a power plant. Finally, we present summary
      findings of the landscape of capture technologies using an index of technology
      readiness levels.

PMID- 21905744
TI  - Solid-phase synthesis of smac peptidomimetics incorporating triazoloprolines and
      biarylalanines.
AB  - Apoptotic induction mechanisms are of crucial importance for the general
      homeostasis of multicellular organisms. In cancer the apoptotic pathways are
      downregulated, which, at least partly, is due to an abundance of inhibitors of
      apoptosis proteins (IAPs) that block the apoptotic cascade by deactivating
      proteolytic caspases. The Smac protein has an antagonistic effect on IAPs, thus
      providing structural clues for the synthesis of new pro-apoptotic compounds.
      Herein, we report a solid-phase approach for the synthesis of Smac-derived
      tetrapeptide libraries. On the basis of a common (N-Me)AVPF sequence, peptides
      incorporating triazoloprolines and biarylalanines were synthesized by means of
      Cu(I)-catalyzed azide-alkyne cycloaddition and Pd-catalyzed Suzuki cross-coupling
      reactions. Solid-phase procedures were optimized to high efficiency, thus
      accessing all products in excellent crude purities and yields (both typically
      above 90%). The peptides were subjected to biological evaluation in a live/dead
      cellular assay which revealed that structural decorations on the AVPF sequence
      indeed are highly important for cytotoxicity toward HeLa cells.

PMID- 21905743
TI  - Hydrazide reactive peptide tags for site-specific protein labeling.
AB  - New site-specific protein labeling (SSPL) reactions for targeting-specific, short
      peptides could be useful for the real-time detection of proteins inside of living
      cells. One SSPL approach matches bioorthogonal reagents with complementary
      peptides. Here, hydrazide reactive peptides were selected from phage-displayed
      libraries using reaction-based selections. Selection conditions included washes
      of varying pH and treatment with NaCNBH(3) in order to specifically select
      reactive carbonyl-containing peptides. Selected peptides were fused to T4
      lysozyme or synthesized on filter paper for colorimetric assays of the peptide
      hydrazide interaction. A peptide-lysozyme protein fusion demonstrated specific,
      covalent labeling by the hydrazide reactive (HyRe) peptides in crude bacterial
      cell lysates, sufficient for the specific detection of an overexpressed protein
      fusion. Chemical synthesis of a short HyRe tag variant and subsequent reaction
      with two structurally distinct hydrazide probes produced covalent adducts
      observable by MALDI-TOF MS and MS/MS. Rather than isolating reactive carbonyl
      containing peptides, we observed reaction with the N-terminal His of HyRe tag
      114, amino acid sequence HKSNHSSKNRE, which attacks the hydrazide carbonyl at
      neutral pH. However, at the pH used during selection wash steps (<6.0), an
      alternative imine-containing product is formed that can be reduced with sodium
      cyanoborohydride. MSMS further reveals that this low pH product forms an adduct
      on Ser6. Further optimization of the novel bimolecular reaction described here
      could provide a useful tool for in vivo protein labeling and bioconjugate
      synthesis. The reported selection and screening methods could be widely
      applicable to the identification of peptides capable of other site-specific
      protein labeling reactions with bioorthogonal reagents.

PMID- 21905746
TI  - Amplified multiplexed analysis of DNA by the exonuclease III-catalyzed
      regeneration of the target DNA in the presence of functionalized semiconductor
      quantum dots.
AB  - Quantum dots (QDs) functionalized with a black-hole quencher are used as optical
      tracer for the detection of DNA using exonuclease as a biocatalyst. The binding
      of the target DNA or of a target/open hairpin complex to the functionalized QDs
      leads to the exonuclease-stimulated recycling of the target DNA or the
      target/hairpin complex. This results in the triggering of the luminescence of the
      QDs that provides a readout signal for the amplified sensing process. By using
      different-sized QDs, the multiplexed detection of DNAs is demonstrated.

PMID- 21905747
TI  - Diastereoselective one-pot synthesis of 7- and 8-substituted 5-phenylmorphans.
AB  - Novel 7- and 8-alkyl and aryl substituted 5-phenylmorphans were synthesized from
      substituted allyl halides and N-benzyl-4-aryl-1,2,3,6-tetrahydropyridine by a
      highly efficient and diastereoselective reaction series, "one-pot" alkylation and
      ene-imine cyclization followed by sodium borohydride reduction. Mild cyclization
      conditions gave the desired substituted 5-phenylmorphans in good yield as a
      single diastereomer.

PMID- 21905749
TI  - Selective synthesis of hydroxy analogues of valinomycin using dioxiranes.
AB  - A synthesis of representative monohydroxy derivatives of valinomycin (VLM) was
      achieved under mild conditions by direct hydroxylation at the side chains of the
      macrocyclic substrate using dioxiranes. Results demonstrate that the powerful
      methyl(trifluoromethyl)dioxirane 1b should be the reagent of choice to carry out
      these key transformations. Thus, a mixture of compounds derived from the direct
      dioxirane attack at the beta-(CH(3))(2)C-H alkyl chain of one Hyi residue
      (compound 3a) or of one Val moiety (compounds 3b and 3c) could be obtained.
      Following convenient mixture separation, each of the new oxyfunctionalized
      macrocycles became completely characterized.

PMID- 21905748
TI  - Stereoselective borylative ketone-diene coupling.
AB  - In the presence of catalytic Ni(cod)(2) and P(t-Bu)(3), ketones, dienes, and
      B(2)(pin)(2) undergo a stereoselective multicomponent coupling reaction. Upon
      oxidation, the reaction furnishes 1,3-diols as the major reaction product.

PMID- 21905750
TI  - Dynamic metabolic response of mice to acute mequindox exposure.
AB  - Mequindox is used as a veterinary antibiotic drug. As part of systematic
      investigations into mequindox as a veterinary medicine and its subsequent
      applications in food safety, we conducted the investigation to assess the
      metabolic response of mice to mequindox using metabonomics, which combines NMR
      metabolic profiles of biofluids or tissues and pattern recognition data analysis.
      In this study, we delivered a single dose of mequindox to mice with dosage levels
      of 15, 75, and 350 mg/kg body weight and collected urine samples over a 7 day
      period, as well as plasma and liver tissues at 7 days postdose. Principal
      components analysis (PCA) and orthogonal projection to latent structure
      discriminant analysis (O-PLS-DA) were performed on (1)H NMR spectra of biofluids
      and liver, showing that low dose levels of mequindox exposure had no adverse
      effects, consistent with histological observations of the liver. High and
      moderate levels of mequindox exposure caused suppression of glycolysis and
      stimulation of fatty acid oxidation accompanied with increased levels of
      oxidative stress. Our metabonomic analyses also showed disruption of amino acid
      metabolism, consistent with liver damage observed from histopathological
      examinations. Furthermore, mequindox perturbed gut microbial activity manifested
      in the altered excretion of urinary trimethylamine (TMA), trimethylamine-N-oxide
      (TMAO), hippurate, phenylacetylglycine (PAG), and phenylacetate. The putative gut
      microbial function may also contribute to the assembly and secretion of very-low
      density lipoproteins from the liver to the plasma. Our work provides important
      insights on the metabolic responses of mequindox.

PMID- 21905751
TI  - Metabolomics unveils urinary changes in subjects with metabolic syndrome
      following 12-week nut consumption.
AB  - Through an HPLC-Q-TOF-MS-driven nontargeted metabolomics approach, we aimed to
      discriminate changes in the urinary metabolome of subjects with metabolic
      syndrome (MetS), following 12 weeks of mixed nuts consumption (30 g/day),
      compared to sex- and age-matched individuals given a control diet. The urinary
      metabolome corresponding to the nut-enriched diet clearly clustered in a distinct
      group, and the multivariate data analysis discriminated relevant mass features in
      this separation. Metabolites corresponding to the discriminating ions (MS
      features) were then subjected to multiple tandem mass spectrometry experiments
      using LC-ITD-FT-MS, to confirm their putative identification. The metabolomics
      approach revealed 20 potential markers of nut intake, including fatty acid
      conjugated metabolites, phase II and microbial-derived phenolic metabolites, and
      serotonin metabolites. An increased excretion of serotonin metabolites was
      associated for the first time with nut consumption. Additionally, the detection
      of urinary markers of gut microbial and phase II metabolism of nut polyphenols
      confirmed the understanding of their bioavailability and bioactivity as a
      priority area of research in the determination of the health effects derived from
      nut consumption. The results confirmed how a nontargeted metabolomics strategy
      may help to access unexplored metabolic pathways impacted by diet, thereby
      raising prospects for new intervention targets.

PMID- 21905752
TI  - Tridentate lysine-based fluorescent sensor for Hg(II) in aqueous solution.
AB  - A novel homoplastic podand fluorescent sensor based on flexible hydrophilic
      lysine was prepared. Lysine with two dansyl groups-appended at both ends supplied
      a possibility for a tridentate binding toward Hg(II) and finally resulted in a
      unique selectivity to Hg(II) over other transition-metal ions with a
      hypersensitivity (detection limit 2.0 nM) in neutral buffered aqueous solutions.
      Notably, the coordination of chloride ion to the complex of sensor-Hg(II) brought
      forth that the trend in the NMR chemical shift for hydrogen and carbon atoms of
      the sensor was contrary to the findings in the former reports, which shows
      upfield shifts for the hydrogens and the alkane carbons but downfield shifts for
      the dansyl carbons, respectively.

PMID- 21905753
TI  - A highly selective on/off fluorescence sensor for cadmium(II).
AB  - A polypyridyl ligand, 2,3,6,7,10,11-hexakis(2-pyridyl)dipyrazino[2,3-f:2',3'
      h]quinoxaline (HPDQ), was found to have excellent fluorescent selectivity for
      Cd(2+) over many other metal ions (K(+), Na(+), Ca(2+), Mg(2+), Mn(2+), Fe(2+),
      Ni(2+), Co(2+), Cu(2+), Ag(+), Hg(2+), Zn(2+), and Cr(3+)) based on the
      intramolecular charge-transfer mechanism, which makes HPDQ a potential
      fluorescence sensor or probe for Cd(2+). An obvious color change between HPDQ and
      HPDQ + Cd(2+) can be visually observed by the naked eye. The structure of the
      complex HPDQ-Cd has been characterized by X-ray crystallography. Density
      functional theory calculation results on the HPDQ and HPDQ-Cd complexes could
      explain the experimental results.

PMID- 21905754
TI  - Antiferromagnetic ground state of quantum spins in the synthetic imanite,
      Ca3Ti2Si3O12: the lost child of the garnet family.
AB  - Large single crystals of the garnet imanite, Ca(3)Ti(2)Si(3)O(12), were
      synthesized by a floating zone technique. Near-infrared to visible spectroscopy
      presents an optical gap of 1.65 eV at 4 K, proving the insulating character of
      this garnet compound. Electron paramagnetic resonance data indicate that the d(1)
      electron of Ti(3+) exhibits an orbital contribution to the spin moment (g =
      1.859(1)). An antiferromagnetic state is observed below T(N) = 7 K, confirmed by
      magnetic susceptibility and specific heat data. X-ray diffraction investigations
      on powders and single crystals of imanite reveal that the crystal structure
      agrees well with expectations: the cubic symmetry Ia3d describes all obtained
      single crystal and powder diffraction data.

PMID- 21905755
TI  - Site-preferential design of itinerant ferromagnetic borides: experimental and
      theoretical investigation of MRh6B3 (M = Fe, Co).
AB  - Single-phase polycrystalline samples of the compounds MRh(6)B(3) (M = Fe, Co) as
      well as single crystals of CoRh(6)B(3) have been synthesized by arc-melting the
      elements under a purified argon atmosphere in a water-cooled copper crucible. The
      characterization of the new phases was achieved by using single-crystal and
      powder X-ray diffraction as well as EDX measurements. The two phases are isotypic
      and crystallize in the hexagonal Th(7)Fe(3) structure type (space group P6(3)mc,
      no. 186, Z = 2). In this structure, the magnetically active atoms (Fe, Co) are
      preferentially found on only one of the three available rhodium sites, and
      together with rhodium they build a three-dimensional network of interconnected
      (Rh/M)(3) triangles. Magnetic properties investigations show that both phases
      order ferromagnetically below Curie temperatures of 240 K (for FeRh(6)B(3)) and
      150 K (for CoRh(6)B(3)). First-principles DFT calculations correctly reproduce
      not only the lattice parameters but also the ground state magnetic ordering in
      the two phases. These calculations also show that the long-range magnetic
      ordering in both phases occurs via indirect ferromagnetic coupling between the
      iron atoms mediated by rhodium. This magnetic structural model also predicts the
      saturation magnetizations to be 4.02 MU(B) for FeRh(6)B(3) (3.60 MU(B) found
      experimentally) and 2.75 MU(B) for CoRh(6)B(3). Furthermore, both phases are
      predicted to be metallic conductors as expected for these intermetallic borides.

PMID- 21905756
TI  - Ba4KFe3O9: a novel ferrite containing discrete 6-membered rings of corner-sharing
      FeO4 tetrahedra.
AB  - Single crystals of a new iron-containing oxide, Ba(4)KFe(3)O(9), were grown from
      a hydroxide melt, and the crystal structure was determined by single-crystal X
      ray diffraction. This ferrite represents the first complex oxide containing
      isolated 6-membered rings of corner-sharing FeO(4) tetrahedra. Mossbauer
      measurements are indicative of two tetrahedral high-spin Fe(3+) coordination
      environments. The observed magnetic moment (~3.9 MU(B)) at 400 K is significantly
      lower than the calculated spin-only (~5.2 MU(B)) value, indicating the presence
      of strong antiferromagnetic interactions in the oxide. Our density functional
      theory calculations confirm the strong antiferromagnetic coupling between
      adjacent Fe(3+) sites within each 6-membered ring and estimate the nearest
      neighbor spin-exchange integral as ~200 K; next-nearest-neighbor interactions are
      shown to be negligible. The lower than expected effective magnetic moment for
      Ba(4)KFe(3)O(9) calculated from chiT data is explained as resulting from the
      occupation of lower-lying magnetic states in which more spins are paired. X-band
      (9.5 GHz) electron paramagnetic resonance (EPR) spectra of a powder sample
      consist of a single line at g ~ 2.01 that is characteristic of Fe(3+) ions in a
      tetrahedral environment, thus confirming the Mossbauer results. Further analysis
      of the EPR line shape reveals the presence of two types of Fe(6) magnetic species
      with an intensity ratio of ~1:9. Both species have Lorentzian line shapes and
      indistinguishable g factors but differ in their peak-to-peak line widths
      (deltaB(pp)). The line-width ratio deltaB(pp)(major)/deltaB(pp)(minor) ~ 3.6
      correlates well with the ratio of the Weiss constants, theta(minor)/theta(major)
      ~ 4.

PMID- 21905757
TI  - Introducing a magnetic guest to a tetrel-free clathrate: synthesis, structure,
      and properties of Eu(x)Ba(8-x)Cu16P30 (0 <= x <= 1.5).
AB  - The europium-containing clathrate-I Eu(x)Ba(8-x)Cu(16)P(30) was synthesized from
      the elements. Powder X-ray diffraction in combination with energy dispersive X
      ray absorption spectroscopy (EDXS) and metallographic studies showed the
      homogeneity range with x <= 1.5. Determination of the crystal structure confirmed
      the presence of an orthorhombic superstructure of clathrate-I and revealed that
      Eu atoms exclusively resided in small pentagonal-dodecahedral cages. Magnetic
      measurements together with X-ray absorption spectroscopy are consistent with a
      4f(7) (Eu(2+)) ground state for Eu(x)Ba(8-x)Cu(16)P(30). Below 3 K the Eu moments
      order antiferromagnetically. Resistivity measurements revealed metallic behavior
      of the investigated clathrate, in line with the composition deviating from the
      Zintl counting scheme. Local vibrations of the guest atoms inside the cages are
      analyzed with the help of specific heat investigations.

PMID- 21905759
TI  - Critical assessment of belgian reimbursement dossiers of orphan drugs.
AB  - BACKGROUND: Orphan medicinal products are designed to diagnose or treat rare
      diseases that are serious, life threatening or chronically debilitating and that
      affect 50 or fewer people in every 100 000 in the EU. In Belgium, the Drug
      Reimbursement Committee (DRC) evaluates reimbursement requests for orphan drugs
      based on multiple criteria: the therapeutic value, price and proposed
      reimbursement tariff; the importance of the drug in clinical practice; and the
      budget impact of the drug. OBJECTIVES: This study aimed to assess reimbursement
      dossiers of orphan drugs in Belgium and to compare them with the clinical
      evidence submitted to the European Medicines Agency (EMA). METHODS: A qualitative
      analysis examined all reimbursement dossiers of orphan drugs that were submitted
      in Belgium between January 2002 and June 2008. The following information was
      extracted from each dossier: description of the orphan drug; indication;
      reimbursement status; therapeutic value and needs; budget impact; and number of
      registered indications. For selected orphan drugs, an in-depth analysis extracted
      and compared information about the clinical trials, their primary endpoints and
      results from EMA documents (i.e. the marketing authorization application file,
      European public assessment report and summary of product characteristics) and the
      Belgian reimbursement dossiers. RESULTS: Reimbursement was awarded to the
      majority of orphan drugs. In addition to the official criteria, other negotiable
      factors, such as price adjustments, employment incentives, patient population
      restrictions and funding of diagnostic tests by the company, seemed to play a
      role in the reimbursement decision. Despite the low number of patients,
      randomized controlled trials were conducted for many orphan drugs. Budget-impact
      analyses were simplistic and did not consider the impact across multiple
      indications. Some differences were also observed between the clinical evidence
      submitted to the EMA and that submitted to the Belgian DRC. CONCLUSIONS: In
      addition to the official criteria, other negotiable factors, such as price
      adjustments and employment incentives, may play a role in Belgian reimbursement
      decisions of orphan drugs. Some differences have also been noted between the
      clinical evidence reported in EMA documents and the evidence included in Belgian
      reimbursement dossiers of orphan drugs. There appears to be a need for further
      standardization of Belgian reimbursement applications and for European
      cooperation in sharing clinical evidence of orphan drugs.

PMID- 21905758
TI  - Balance between fluorescence enhancement and association affinity in fluorescent
      heteroditopic indicators for imaging zinc ion in living cells.
AB  - A fluorescent heteroditopic indicator for the zinc(II) ion possesses two
      different zinc(II) binding sites. The sequential coordination of zinc(II) at the
      two sites can be transmitted into distinct fluorescence changes. In the
      heteroditopic ligand system that our group developed, the formations of mono- and
      dizinc(II) complexes along an increasing gradient of zinc(II) concentration lead
      to fluorescence enhancement and an emission bathochromic shift, respectively. The
      extents of these two changes determine the sensitivity and, ultimately, the
      effectiveness of the heteroditopic indicator in quantifying zinc(II) ion over a
      large concentration range. In this work, a strategy to increase the degree of
      fluorescence enhancement upon the formation of the monozinc(II) complex of a
      heteroditopic ligand under simulated physiological conditions is demonstrated.
      Fluorination of the pyridyl groups in the pentadentate N,N,N'
      tris(pyridylmethyl)ethyleneamino group reduces the apparent pK(a) value of the
      high-affinity site, which increases the degree of fluorescence enhancement as the
      monozinc(II) complex is forming. However, fluorination impairs the coordination
      strength of the high-affinity zinc(II) binding site, which in the triply
      fluorinated ligand reduces the binding strength to the level of the low-affinity
      2,2'-bipyridyl. The potential of the reported ligands in imaging zinc(II) ion in
      living cells was evaluated. The subcellular localization properties of two
      ligands in five organelles were characterized. Both benefits and deficiencies of
      these ligands were revealed, which provides directions for the near future in
      this line of research.

PMID- 21905760
TI  - Diabetes and stress: an anthropological review for study of modernizing
      populations in the US-Mexico border region.
AB  - INTRODUCTION: Diabetes is a growing worldwide problem, characterized by
      considerable ethnic variation and being particularly common in modernizing
      populations. Modernization is accompanied by a variety of stressful sociocultural
      changes that are believed to increase the risk of diabetes. Unfortunately, there
      is little accurate knowledge about impact of stress on the risk of diabetes in
      the US-Mexico border area. METHODS: Literature searches were performed in PubMed
      and Google Scholar to identify anthropological studies on stress and diabetes.
      Snowball and opportunistic sampling were used to expand the identified
      literature. In total, 30 anthropological studies were identified concerning the
      role of stress and modernization on diabetes among Indigenous peoples. This
      article reviews the available information regarding stress and diabetes in
      different populations from various anthropological perspectives. RESULTS: Four
      different concepts of stress were indentified: physiological, psychological,
      psychosocial and nutritional stress. Unlike physiological and nutritional
      theories of diabetes, psychological and psychosocial theories of stress and
      disease lack etiological specificity. No study addressed all four concepts of
      stress and few studies addressed more than two concepts. Most studies concerned
      nutritional stress and the developmental origins of diabetes. Most studies were
      conducted on the Pima Indians of Arizona and Mexico. All four stress concepts
      have some evidence as determinants of diabetes. CONCLUSION: These theoretical
      concepts and ethnographic results can provide the basis for developing
      comprehensive research protocols and public health intervention targeted at
      diabetes. A comprehensive view of stress can potentially explain the high
      prevalence of diabetes in developing countries and among Indigenous peoples.
      These results can be used to inform public health interventions aimed at reducing
      diabetes in the US-Mexico border region or similar areas, help identify at-risk
      individuals, and guide health education and promotion.

PMID- 21905761
TI  - Quality of life following successful repair of vesicovaginal fistula in Nigeria.
AB  - INTRODUCTION: The impact of obstetric vesicovaginal fistula (VVF), which
      continues to occur among women in developing countries, can severely affect the
      health of the women while the condition persists. This study was designed to
      discover the effect of successful VVF repair on affected women's quality of life.
      METHODS: A comparison of the quality of life of a cross-section of women who had
      VVF was carried out before and 6 months after successful repair. Quality of life
      was assessed using the WHO Quality of Life (WHOQOL)-BREF Questionnaire. RESULTS:
      Of the 150 women studied, only 20% felt satisfied with their general state of
      health and quality of life before the repair, while this increased to 90%
      following successful repair (highly statistically significant at p<0.000). In the
      physical health domain, the mean quality of life score was 67.9 +/- 4.4 before
      and 69.3 +/- 3.4 after successful repair (p<0.01). In the mental health domain,
      the mean quality of life score was 32.4 +/- 8.7 before and 74.7 +/- 3.2 after
      successful repair (p<0.005). In the social health domain, the mean score was 20.2
      +/- 2.7 before and 69.7 +/- 2.3 after successful repair (p<0.001). In the
      environment domain, the mean score of quality of life was 60.3 +/- 4.3 before
      repair and 59.7 +/- 2.7 after successful repair (comparable at p<0.2).
      CONCLUSION: Successful repair of VVF is associated with significant improvement
      in the multidimensional quality of life among affected women.

PMID- 21905762
TI  - Novel phosphodiesterase type 5 modulators: a patent survey (2008 - 2010).
AB  - INTRODUCTION: The inhibition of cyclic nucleotide PDE5 has been clinically
      validated as an effective treatment for erectile dysfunction and pulmonary
      arterial hypertension. There are three PDE5 inhibitors (sildenafil, vardenafil
      and tadalafil) approved worldwide and a further two agents (udenafil and
      mirodenafil) approved only in Korea. These first generation agents are perceived
      to have flaws in selectivity over other PDEs: slow onset, duration of action or
      CNS penetration, which has driven further research to identify optimal PDE5
      inhibitors for the current pathologies. Several clinical trials have been
      reported to investigate the potential for PDE5 inhibitors to treat additional
      indications, which might require agents with different biological and/or
      pharmacokinetic profiles. AREAS COVERED: This review provides a summary of
      developments in the patent and open literature over the period 2008 - 2010.
      EXPERT OPINION: Avanafil, the first of a new generation of PDE5 inhibitors, has
      shown encouraging efficacy in clinical trials, and is likely to result in a new
      drug application filing during 2011, followed by a possible launch in 2012.
      Judging by the wealth of different structural series being claimed in patents, it
      seems that the selectivity and pharmacokinetic issues facing the first generation
      can be addressed through novel chemical matter.

PMID- 21905763
TI  - The COPD Pipeline XII.

PMID- 21905764
TI  - Emerging GLP-1 receptor agonists.
AB  - INTRODUCTION: Recently, glucagon-like peptide-1 receptor (GLP-1R) agonists have
      become available for the treatment of type 2 diabetes. These agents exploit the
      physiological effects of GLP-1, which is able to address several of the
      pathophysiological features of type 2 diabetes. GLP-1R agonists presently
      available are administered once or twice daily, but several once-weekly GLP-1R
      agonists are in late clinical development. AREAS COVERED: The present review aims
      to give an overview of the clinical data on the currently available GLP-1R
      agonists used for treatment of type 2 diabetes, exenatide and liraglutide, as
      well as the emerging GLP-1R agonists including the long-acting compounds. EXPERT
      OPINION: An emerging therapeutic trend toward initial or early combination
      therapy with metformin- and incretin-based therapy is anticipated for patients
      with type 2 diabetes. GLP-1-based therapy has so far proven safe and tolerable.
      The determination of which incretin-based therapy to choose necessitates
      comparisons between the various GLP-1R agonists. The available GLP-1R agonists
      cause sustained weight loss and clinical relevant improvement of glycemic
      control. The long-acting GLP-1R agonists in late development may improve the
      effects of GLP-1 even further with optimized pharmacokinetic profiles resulting
      in fewer side effects. Meta-analyses have shown promising effects on
      cardiovascular disease and data from ongoing multicenter trials with
      cardiovascular endpoints are expected in 2015.

PMID- 21905765
TI  - Successful treatment with oral valganciclovir of primary CMV enterocolitis in a
      congenitally infected infant.
AB  - Cytomegalovirus (CMV) is the most common congenitally acquired viral infection in
      the United States and is associated with significant morbidity and mortality.
      Primary CMV enterocolitis is well documented in immunocompromised patients, but
      remains rare in congenitally acquired infections. There are no universally
      accepted recommendations for the treatment of CMV enterocolitis in the pediatric
      population. Case reports show varied dosing and length of treatment of either
      intravenously administered ganciclovir, orally administered valganciclovir, or a
      combination of both. We present a congenitally infected infant with primary CMV
      enterocolitis who was successfully treated with orally administered
      valganciclovir.

PMID- 21905766
TI  - Ophthalmic preservatives: focus on polyquaternium-1.
AB  - INTRODUCTION: Ophthalmic preservatives, such as polyquaternium-1 (PQ-1), are
      critical for the inhibition of growth of microbial contaminants in multi-dose
      bottles of topical medications. These antimicrobial agents must have a high
      efficacy against pathogenic organisms, while maintaining a favorable tolerability
      and safety profile. AREAS COVERED: This review focuses on the ophthalmic
      preservative PQ-1. For comparison purposes, the most commonly used preservative,
      benzalkonium chloride (BAK), is also discussed. This survey focuses primarily on
      data collected during the past 10 years. EXPERT OPINION: Effective drug delivery
      requires more than just an active ingredient that achieves its desired biological
      effect on end-target tissues. In addition, drugs must be stable in the containers
      that they are stored in, and must possess minimal undesired local and systemic
      side effects that can cause patients to decrease their adherence. In addressing
      these concerns, specifically in topical ophthalmic drops, one must take into
      account the active ingredients, vehicle components and preservatives. Medications
      with fewer adverse effects may lead to enhanced adherence to therapy; therefore,
      the induction of such adverse outcomes must be considered by physicians when
      treating patients with chronic ocular disease. Although BAK will continue to be
      used in ophthalmic medications, due to its familiarity and compatibility with a
      broad range of topical ocular formulations, PQ-1 is certainly a viable
      alternative in the preservative formulary armamentarium.

PMID- 21905767
TI  - Cytogenetic characterization of the invasive mussel species Xenostrobus securis
      Lmk. (Bivalvia: Mytilidae).
AB  - The chromosomes of the invasive black-pigmy mussel (Xenostrobus securis (Lmk.
      1819)) were analyzed by means of 4',6-diamidino-2-phenylindole (DAPI) / propidium
      iodide (PI) and chromomycin A3 (CMA) / DAPI fluorescence staining and fluorescent
      in situ hybridization using major rDNA, 5S rDNA, core histone genes, linker
      histone genes, and telomeric sequences as probes. The diploid chromosome number
      in this species is 2n = 30. The karyotype is composed of seven metacentric, one
      meta/submetacentric, and seven submetacentric chromosome pairs. Telomeric
      sequences appear at both ends of every single chromosome. Major rDNA clusters
      appear near the centromeres on chromosome pairs 1 and 3 and are associated with
      bright CMA fluorescence and dull DAPI fluorescence. This species shows five 5S
      rDNA clusters close to the centromeres on four chromosome pairs (2, 5, 6, and 8).
      Three of the four core histone gene clusters map to centromeric positions on
      chromosome pairs 7, 10, and 13. The fourth core histone gene cluster occupies a
      terminal position on chromosome pair 8, also bearing a 5S rDNA cluster. The two
      linker histone gene clusters are close to the centromeres on chromosome pairs 12
      and 14. Therefore, the use of these probes allows the unequivocal identification
      of 11 of the 15 chromosome pairs that compose the karyotype of X. securis.

PMID- 21905768
TI  - A genetic map of an Australian wild Gossypium C genome and assignment of
      homoeologies with tetraploid cultivated cotton.
AB  - Genetic diversity for traits such as fibre quality or disease resistance to
      microorganisms is limited in the elite cotton germplasm; consequently, cotton
      breeders are looking for novel alleles in the secondary or even in the tertiary
      gene pools. The wild Australian Gossypium species (tertiary gene pool) represent
      an alternative source of novel alleles. However, to use these species
      efficiently, enabling tools are required. Chromosome-specific molecular markers
      are particularly useful tools to track the transmission of this exotic genetic
      material into the cultivated cotton during introgression. In this study, we
      report the construction of a genetic linkage map of the Australian wild C-genome
      species Gossypium sturtianum. The map, based on an F(2) population of 114
      individuals, contains 291 AFLP loci. The map spans 1697 cM with an average
      distance of 5.8 cM between markers. To associate C-genome chromosomes with the A
      and D subgenomes of cultivated cotton, 29 SSR and RFLP-STS markers were assigned
      to chromosomes using cultivated cotton mapped marker information. Polymorphisms
      were revealed by 51 AFLP primer combinations and 38 RFLP-STS and 115 SSR cotton
      mapped markers. The utility of transferring RFLP-STS and SSR cotton mapped
      markers to other Gossypium species shows the usefulness of a comparative approach
      as a source of markers and for aligning the genetic map of G. sturtianum with the
      cultivated species in the future. This also indicates that the overall structure
      of the G. sturtianum linkage groups is similar to that of the A and D subgenomes
      of cotton at the gross structural level. Applications of the map for the
      Australia wild C-genome species and cotton breeding are discussed.

PMID- 21905769
TI  - Preoperative "group and save" in lumbar microdiscectomy: is it necessary?
AB  - OBJECT: "Group and save" (type and screen) is commonly requested preoperatively
      in lumbar microdiscectomy. On average, less than 100 ml of blood is lost during
      lumbar microdiscectomy, and blood transfusion guidelines and resuscitation
      practice recommend that no transfusion would be required in almost all healthy
      patients with less than 750 ml of blood loss. The authors performed an audit of
      319 consecutive lumbar microdiscectomies to determine if the practice of group
      and save can be justified. A telephone survey of the United Kingdom (UK)
      neurosurgical units to establish current UK neurosurgical practice was also
      conducted. METHODS: A telephone survey of all UK neurosurgical units and an audit
      of all patients who underwent primary lumbar microdiscectomy at our institution
      over a period of 2 consecutive years was performed. The health records of all
      patients were retrieved and critically reviewed. Information about hemoglobin
      measurements before and after surgery, group and save, and blood transfusion were
      collected. RESULTS: Thirty-two UK neurosurgical units were surveyed by telephone,
      with a 100% response rate. Group and save was commonly performed prior to lumbar
      microdiscectomy in 28 units (87.5%). The records of 319 consecutive patients who
      underwent lumber microdiscectomy were reviewed. All patients had group and save
      prior to lumbar microdiscectomy. No patient required a blood transfusion during
      or after surgery. The mean decrease in hemoglobin concentration was 0.8 g/dl in
      121 patients who had postoperative hemoglobin measurements. CONCLUSIONS: Blood
      transfusion and hemoglobin decrease following lumbar microdiscectomy is
      exceptionally rare. Group and save and postoperative hemoglobin measurements are
      therefore nonessential in all patients undergoing lumbar microdiscectomy, with
      potentially significant cost savings from not performing these tests.

PMID- 21905770
TI  - Subarachnoid hemorrhage due to retained lumbar drain.
AB  - Intrathecal spinal catheters (lumbar drains) are indicated for several medical
      and surgical conditions. In neurosurgical procedures, they are used to reduce
      intracranial and intrathecal pressures by diverting CSF. They have also been
      placed for therapeutic access to administer drugs, and more recently, vascular
      surgeons have used them to improve spinal cord perfusion during the treatment of
      thoracic aortic aneurysms. Insertion of these lumbar drains is not without
      attendant complications. One complication is the shearing of the distal end of
      the catheter with a resultant retained fragment. The authors report the case of a
      65-year-old man who presented with a subarachnoid hemorrhage due to the migration
      of a retained lumbar drain that sheared off during its removal. To the best of
      the authors' knowledge, this is the first case of rostral migration of a retained
      intrathecal catheter causing subarachnoid hemorrhage. The authors review the
      literature on retained intrathecal spinal catheters, and their findings support
      either early removal of easily accessible catheters or close monitoring with
      serial imaging.

PMID- 21905771
TI  - Analysis of ascending spinal tract degeneration in cervical spondylotic
      myelopathy using 3D anisotropy contrast single-shot echo planar imaging on a 3.0
      T system.
AB  - OBJECT: The authors assessed the role of 3D anisotropy contrast (3DAC) in
      evaluating specific ascending tract degeneration in patients with cervical
      spondylotic myelopathy (CSM). METHODS: The authors studied 10 patients (2 women,
      8 men; mean age 59.8 +/- 14.6 years) with CSM and spinal cord compression below
      the C2-3 disc level, as well as 10 healthy control individuals (3 women, 7 men;
      mean age 42.0 +/- 24.1 years). Images of the cervical cord at the C2-3 level were
      obtained using a 3.0-T MR imaging system. RESULTS: Three-dimensional anisotropy
      contrast imaging clearly made possible tract-by-tract analysis of the fasciculus
      cuneatus, fasciculus gracilis, and spinocerebellar tract. Tract degeneration
      identified using 3DAC showed good correlation with a decline in fractional
      anisotropy. Degeneration of the fasciculus gracilis detected by "vector contrast"
      demonstrated a good correlation with Nurick grades. CONCLUSIONS: The study
      unambiguously demonstrated that 3DAC imaging is capable of assessing ascending
      tract degeneration in patients with CSM. Degeneration of an individual tract can
      be easily identified as a vector contrast change on the 3DAC image, a reflection
      of quantitative changes in anisotropism, similar to fractional anisotropy.
      Excellent correlation between Nurick grades and fasciculus gracilis degeneration
      suggests potential application of 3DAC imaging for tract-by-tract clinical
      correlation.

PMID- 21905772
TI  - The use of 3D computer graphics in the diagnosis and treatment of spinal vascular
      malformations.
AB  - OBJECT: Digital subtraction (DS) angiography is the gold standard for diagnosing
      spinal vascular malformations. Recently, multidetectorrow spiral CT and contrast
      enhanced MR angiography have been introduced as screening examinations before DS
      angiography. These methods, however, do not always determine the accurate
      location of an arteriovenous shunt because the resulting images lack information
      about the spinal cord or the dura mater. METHODS: Between April 2009 and December
      2010, 13 patients underwent imaging evaluations for spinal vascular malformations
      at the authors' university hospital. This group included 8 patients with spinal
      dural arteriovenous fistulas (AVFs), 3 with perimedullary AVFs, and 2 with
      intramedullary arteriovenous malformations. Using data from these patients, the
      authors attempted to develop 3D computer graphics (CG) based upon the fusion of
      3D rotational angiography and postmyelographic CT. They subsequently verified the
      accuracy of this imaging method. Ten of these 13 patients underwent surgical
      treatment for their lesions (11 AVFs), and for these 11 lesions the authors
      compared the diagnoses obtained using 3D CG with those obtained using
      conventional DS angiography. RESULTS: In all 13 cases, 3D CG images of the spinal
      lesions were successfully developed using the patients' actual data. Four (36%)
      of 11 AVFs were correctly identified using DS angiography, whereas 10 (91%) were
      correctly identified using 3D CG. Results from 3D CG of spinal AVFs corresponded
      well with operative findings, and 3D CG was significantly better than
      conventional DS angiography at predicting AVF location (p = 0.024, Fisher exact
      test). CONCLUSIONS: To the authors' knowledge, this is the first reported case
      series in which 3D CG of spinal vascular malformations was used to provide
      simultaneous, stereoscopic visualization of the spinal vascular system, spinal
      cord, dura mater, and bone. The 3D CG method provides precise visual images for
      the diagnosis and treatment of these lesions.

PMID- 21905773
TI  - The effects of chemotherapeutic agents on differentiated chordoma cells.
AB  - OBJECT: Chordoma is a rare type of malignant bone tumor and is known to arise
      from the remnants of the notochord. Resistance to chemotherapy makes the
      treatment of chordoma difficult; therefore, new approaches need to be developed
      to cure this disease. Differentiation therapy, using various differentiating
      agents, is attracting oncologists as a common therapeutic method to treat other
      tumors. Based on forcing cells to mature into other lineages, differentiation
      therapy might be an available method to treat chordomas in addition to
      conventional therapies. METHODS: In this study a chordoma cell line, U-CH1, was
      exposed to several chemotherapeutic agents including vincristine, doxorubicin,
      cisplatin, etoposide, fludarabine, methotrexate, nilotinib, and imatinib mesylate
      under appropriate conditions. The first group of U-CH1 cells was exposed to drugs
      only and the second group of cells was exposed to the simultaneous treatment of 1
      MUM all-trans retinoic acid (ATRA) and chemotherapeutic agents in differentiation
      therapy. The efficacy of the differentiation method was assessed by measuring the
      viability of U-CH1 cells. RESULTS: Vincristine, doxorubicin, etoposide,
      cisplatin, and fludarabine, each at a concentration of 10 MUM, decreased the
      number of chordoma cells when given alone down to 11%, 0%, 30%, 67%, and 3%,
      respectively. Etoposide and cisplatin, each at a concentration of 10 MUM, reduced
      the percentage of viable chordoma cells in a more effective way when given with 1
      MUM ATRA simultaneously, reducing the number of viable cells to 14% and 9%,
      respectively. On the other hand, imatinib and nilotinib, each at a concentration
      of 3 MUM, as well as 10 MUM methotrexate, showed no decrease in the number of
      cancer cells. CONCLUSIONS: The results suggest that chordoma cells may be treated
      using the differentiation method in a more effective way than when they are
      treated with chemotherapeutic agents alone. This new approach may be an
      alternative method to conventional therapies in the treatment of chordoma.

PMID- 21905774
TI  - Novel spinal cord imaging.

PMID- 21905775
TI  - The V(2) segment of the vertebral artery: anatomical considerations and surgical
      implications.
AB  - OBJECT: Iatrogenic injury of the V(2) segment of the vertebral artery (VA) is a
      rare but serious complication and can be catastrophic. The purpose of this study
      was to characterize the relationship of the V(2) segment of the VA to the
      surrounding anatomical structures and to highlight the potential site and
      mechanisms of injury that can occur during common neurosurgical procedures
      involving the subaxial cervical spine. METHODS: Ten adult cadaveric specimens (20
      sides) were included in this study. Quantitative anatomical measurements between
      selected landmarks and the VA were obtained. In addition, lateral mass screws
      were placed bilaterally, from C-3 to C-7, reproducing either the Magerl technique
      or a modified technique. The safety angle, defined as the axial deviation from
      the screw trajectory needed to injure the VA, and the distance from the entry
      point to the VA were measured at each level for both techniques. RESULTS: The VA
      coursed closer to the midline at C3-4 and C4-5 (mean distance [SD] 14.9 +/- 1.1
      mm) than at C2-3 or C5-6. Within the intertransverse space it coursed closer to
      the uncinate processes of the vertebral bodies (1.8 +/- 1.1 mm) than to the
      anterior tubercle of the transverse processes (3.4 +/- 1.6 mm). The distance
      between the VA and the uncinate process was less at C3-6 (1.3 +/- 0.7 mm) than at
      C2-3 (3.3 +/- 0.8 mm). The VA coursed on average at a distance of 11.9 +/- 1.7 mm
      from the anterior and 4.2 +/- 2.6 mm from the posterior aspect of the
      intervertebral disc space. Lateral mass screw angles were 25 degrees  lateral and
      39.1 degrees  cranial for the Magerl technique, and 36.6 degrees  lateral and
      46.1 degrees  cranial for the modified technique. The safety angle was greater
      and screw length longer when using this modified technique. CONCLUSIONS: The
      relation of the V(2) segment of the VA to anterior procedures and lateral mass
      instrumentation at the subaxial cervical spine was reviewed in this study. A
      detailed anatomical knowledge of the V(2) segment of the VA combined with careful
      preoperative imaging is mandatory for safe cervical spine surgery.

PMID- 21905776
TI  - Analysis of in vivo kinematics of 3 different cervical devices: Bryan disc,
      ProDisc-C, and Prestige LP disc.
AB  - OBJECT: Cervical arthroplasty has emerged as a means of preventing adjacent
      segment disease by preserving motion, restoring sagittal balance, and mimicking
      natural spinal kinematics. The purpose of this retrospective in vivo study was to
      characterize the impact of arthroplasty on sagittal balance and segmental
      kinematics of the cervical spine. METHODS: Sixty patients receiving the Bryan
      disc, ProDisc-C, or Prestige LP disc were retrospectively analyzed. Only single
      level arthroplasty cases were included in this study. Lateral dynamic radiographs
      of the cervical spine were evaluated using quantitative measurement analysis
      software to determine the kinematics at the index level both preoperatively and 1
      year postoperatively. Collected parameters included range of motion (ROM), disc
      angles, shell angles, anterior and posterior disc heights (ADHs/PDHs),
      translation, and center of rotation (COR). Preoperative and postoperative data
      were compared using the Student t-test, with p < 0.05 indicating significance.
      RESULTS: The Bryan and Prestige LP discs preserved motion, whereas the ProDisc-C
      increased segmental ROM from extension to flexion. Following surgery, the Bryan
      disc exhibited significant shell angle kyphosis, while ProDisc-C and Prestige LP
      retained lordosis. Both ADHs and PDHs decreased following insertion of the Bryan
      disc. In contrast, the ProDisc-C increased the ADHs and PDHs by 80% and 52%,
      respectively, and the Prestige LP disc increased the ADHs and PDHs by 20%. Only
      the ProDisc-C demonstrated significant translation of 0.7 mm. The ProDisc-C
      shifted the COR x by 0.9 mm anteriorly, while the Prestige LP disc demonstrated a
      significant superior shift of 2.2 mm in COR y. CONCLUSIONS: All discs adequately
      maintained ROM at the surgical level. The greatest difference among the 3 devices
      was in the disc height and index angle measurements.

PMID- 21905777
TI  - Will direct-acting antivirals make a difference in HIV-HCV coinfected patients?

PMID- 21905778
TI  - Prenatal prevention of respiratory syncytial virus bronchiolitis.

PMID- 21905779
TI  - How could rapid bacterial identification improve the management of septic
      patients?

PMID- 21905781
TI  - Preventing deaths from cryptococcal meningitis: from bench to bedside.
AB  - Cryptococcal meningitis (CM), a fungal disease caused by Cryptococcus spp., is
      the most common form of meningitis and a leading cause of death among persons
      with HIV/AIDS in sub-Saharan Africa. Detection of cryptococcal antigen, which is
      present several weeks before overt signs of meningitis develop, provides an
      opportunity to detect infection early. Screening persons with HIV for
      cryptococcal infection when they access healthcare can identify asymptomatic
      infected patients allowing for prompt treatment and prevention of death. A newly
      developed point-of-care assay for cryptococcal antigen, as well as growing
      evidence supporting the utility and cost-effectiveness of screening, are further
      reasons to consider broad implementation of cryptococcal screening in countries
      with a high burden of cryptococcal disease.

PMID- 21905782
TI  - Tuberculous optochiasmatic arachnoiditis: a devastating form of tuberculous
      meningitis.
AB  - Tuberculous meningitis is primarily a disease of the meninges of brain and spinal
      cord along with adjacent brain parenchyma. The characteristic pathological
      changes are meningeal inflammation, basal exudates, vasculitis and hydrocephalus.
      Tuberculous meningitis has a strong predilection for basal parts of the brain.
      Exudates, if dominantly present in the interpeduncular, suprasellar and Sylvian
      cisterns, result in optochiasmatic arachnoiditis and tuberculoma. Optochiasmatic
      arachnoiditis and tuberculoma are devastating forms of tuberculous meningitis and
      often associated with profound vision loss. This clinical entity more frequently
      affects young adults. In a recent study, on the multivariate logistic regression
      analysis, female sex, younger age and raised cerebrospinal fluid protein content
      were identified as predictors for developing optochiasmatic arachnoiditis.
      Frequently, optochiasmatic tuberculoma and optochiasmatic arachnoiditis develop
      paradoxically while a patient is being treated with anti-TB drugs. MRI reveals
      confluent enhancing lesions that are present in the interpeduncular fossa,
      pontine cistern, and the perimesencephalic and suprasellar cisterns. Management
      of tuberculous optochiasmatic arachnoiditis and optochiasmatic arachnoiditis
      tuberculoma has been variable. Treatment of optochiasmatic arachnoiditis
      continues to be a challenge and the response is generally unsatisfactory. In
      isolated case reports and in small series, corticosteroids, methyl prednisolone,
      thalidomide and hyaluronidase have been used with variable success. The benefit
      from neurosurgery is controversial and deterioration may follow the initial
      temporary improvement. Management of paradoxical optochiasmatic arachnoiditis is
      also controversial. Some patients regain vision following treatment with anti-TB
      drugs and continued usage of corticosteroids. Neurosurgery may be considered in
      the patients with either treatment failure or when diagnosis is in doubt. In
      conclusion, presence of optochiasmatic arachnoiditis or tuberculoma has important
      therapeutic and prognostic implications for patients of tuberculous meningitis.

PMID- 21905784
TI  - Impact of HCV genetic differences on pathobiology of disease.
AB  - Multiple HCV genotypes have been isolated worldwide. Genotype seems to be
      involved in the main pathological aspects of HCV infection. Insulin resistance,
      steatosis and progression toward cirrhosis, fibrosis and hepatocellular carcinoma
      establish and develop following genotype-specific mechanisms. Moreover genotype
      influences pharmacological treatment in term of dose and duration. Pathways
      involved in cell proliferation, apoptosis, lipid metabolism, insulin and
      interferon signaling are impaired to a different extent among genotypes, leading
      to distinct pathological settings. Genotype 1 is associated with a more
      aggressive disease with increased insulin resistance, worst response to therapy,
      higher risk of cirrhosis and hepatocellular carcinoma development, while genotype
      3 is associated with increased steatosis and fibrosis. The identification and
      characterization of HCV types and subtypes provides insight into the different
      outcome of HCV infection and responsiveness to therapy. In the present article,
      we focused on the pathogenicity of HCV genotypes and their effect on disease
      progression and treatment.

PMID- 21905785
TI  - Carriage of Neisseria meningitidis in Europe: a review of studies undertaken in
      the region.
AB  - Meningococcal conjugate vaccines induce herd protection by preventing
      nasopharyngeal meningococcal acquisition, which is a prerequisite for invasive
      disease. Thus, meningococcal carriage epidemiology is important in understanding
      relationships between carriage and disease. A literature search traced
      information on meningococcal carriage in 27 EU countries. Meningococcal carriage
      prevalence differed within and between countries, varying across age groups,
      serogroup distribution and over time. Carriage prevalence increased during
      childhood, peaking in 15-24-year-olds. While serogroup B was usually the dominant
      serogroupable carried serogroup, serogroups C, W-135 and Y were also frequently
      carried. Current carriage studies in Europe are limited. New studies using
      standardized methods are needed to improve our understanding of meningococcal
      disease etiology and transmission, and to monitor the impact of meningococcal
      conjugate vaccines in populations.

PMID- 21905783
TI  - Evidence for a causal relationship between respiratory syncytial virus infection
      and asthma.
AB  - Respiratory syncytial virus (RSV) infects all children early in life, is the most
      common cause of infant lower respiratory tract infections, and causes disease
      exacerbations in children with asthma. Episodes of lower respiratory tract
      infection in early life are associated with asthma development. Whether RSV
      infection early in life directly causes asthma or simply identifies infants who
      are genetically predisposed to develop subsequent wheezing is debatable. Recent
      studies suggest that these two explanations are not mutually exclusive, and are
      likely both important in asthma development. An open-label study of RSV
      immunoprophylaxis administered to preterm infants reduced recurrent wheezing by
      50%. Clinical trials of infant RSV prevention, delay or severity reduction on the
      outcome of childhood asthma would confirm the causal relationship between RSV
      infection and asthma, and offer a primary prevention strategy.

PMID- 21905786
TI  - Bacteriophage therapy: potential uses in the control of antibiotic-resistant
      pathogens.
AB  - The use of bacteriophages (phages) to treat bacterial infections, known as phage
      therapy, has a history substantially longer than that of antibiotics, yet these
      drugs have been the treatment of choice in the West for over 60 years owing to
      efficacy, low toxicity and ease of production. Bacteria are becoming increasingly
      resistant to antibiotics while efforts to discover new agents have drastically
      reduced. Phages have co-evolved with their hosts over billions of years and have
      acquired mechanisms to counter bacterial defences such as extracellular biofilm
      production, which severely reduces the effectiveness of conventional antibiotics.
      Recent animal and human trials show phages to be safe, well-tolerated agents with
      a bright future as an alternative to chemical agents.

PMID- 21905787
TI  - Prosthetic joint infection: diagnosis and management.
AB  - Prosthetic joint implantations improve patients' quality of life but are
      associated with complications, including aseptic failure and prosthetic joint
      infection (PJI). Biofilms are the essential factor in the persistence of
      infection. Early postoperative and acute hematogenous infections are usually
      easily diagnosed; however, late chronic infections are challenging to predict.
      Joint aspiration with differential cell counts appears to be a very useful test.
      New microbiological techniques (i.e., implant sonication and molecular studies)
      are promising tools. Main objectives of treatment are to alleviate pain, to
      restore the function and to eradicate the infection. In deciding the best
      approach for an individual patient, several factors should be considered: the
      type of the infection, presence of loosening, functional prognosis, etiology and
      the patient's preferences. Antimicrobial therapy should be coherent with the
      chosen surgical strategy. Level of evidence in the field of PJI is low, and
      recommendations are based on short literature series, experimental data and
      expert experience.

PMID- 21905789
TI  - Micafungin use in children.
AB  - Invasive fungal infections (IFIs) are one of the major reasons for morbidity and
      mortality in immunocompromised children. The majority of IFIs are caused by
      Candida and Aspergillus species. Early diagnosis and prompt initiation of
      appropriate antifungal therapy is essential for favorable outcome. Micafungin is
      a member of the echinocandins, a novel class of antifungal agents that target the
      biosynthesis of beta-1,3-D-glucan, a key fungal cell wall component. It has
      concentration-dependent fungicidal activity against Candida species and
      fungistatic activity against Aspergillus species. Although optimal dosing of
      micafungin in children has not been established, the recommended dosage in
      children is 2 mg/kg/day (100 mg/day if >40 kg bodyweight) for invasive
      candidiasis, 1 mg/kg/day (50 mg/day if >40 kg bodyweight) for the prophylaxis of
      Candida infections in patients with anticipated prolonged and severe neutropenia
      or in allogeneic hematopoietic stem cell transplantation recipients. Micafungin
      has a favorable safety and drug-drug interaction profile. The most common adverse
      effects in children are diarrhea, epistaxis, abdominal pain, headache, nausea,
      vomiting, fever, chills, elevation of alanine aminotransferase/aspartate
      aminotransferase values, hypokalemia, thrombocytopenia, mucositis, and rash.
      Because of its different mechanisms of action, micafungin shows promise as part
      of the prophylactic and therapeutic management of IFIs, but larger prospective
      and comparative trials are needed for widespread use in children.

PMID- 21905788
TI  - Immunopathogenesis of falciparum malaria: implications for adjunctive therapy in
      the management of severe and cerebral malaria.
AB  - Despite optimal antimalarial treatment and advances in malaria eradication, the
      mortality rate associated with severe malaria due to Plasmodium falciparum
      infection, including cerebral malaria (CM), remains unacceptably high. This
      suggests that strategies directed solely at parasite eradication may be
      insufficient to prevent neurological complications and death in all cases of CM.
      Therefore, there is an urgent need to develop innovative adjunctive therapeutic
      strategies to effectively reduce CM-associated mortality. CM pathogenesis is
      believed to be due, in part, to an aberrant host immune response to P.
      falciparum, resulting in deleterious consequences, including vascular activation
      and dysfunction. Development of effective and affordable therapeutic strategies
      that act to modulate the underlying host-mediated immunopathology should be
      explored to improve outcome. In this article, we summarize immunomodulatory
      therapies that have been assessed in clinical trials to date, and highlight novel
      and promising treatment strategies currently being investigated to address this
      major global health challenge.

PMID- 21905792
TI  - Topical application of betahistine improves eustachian tube function in an animal
      model.
AB  - CONCLUSION: Betahistine dihydrochloride, a drug used widely in the systemic
      treatment of balance disorders such as Meniere's disease, was found to improve
      eustachian tube function when applied topically in the nasopharynx of rats.
      OBJECTIVES: The study tested the effect of betahistine, a histamine receptor
      agonist, on eustachian tube function and tested the involvement of H1 and H3
      histamine receptors. METHODS: Eustachian tube function was measured in
      anaesthetized rats while middle ear pressure was increased and then monitored
      during induced swallowing. Betahistine and other drugs were applied topically in
      the nasopharynx, bulla and epipharynx, and administered intraperitoneally.
      RESULTS: Systemic application of betahistine hardly changed eustachian tube
      function, but topical application significantly improved it. The action of
      topical betahistine was unaffected by the HI receptor antagonist mepyramine and
      was mimicked by the H3 agonist, ciproxifan.

PMID- 21905791
TI  - Three-year follow-up of palatal implants for the treatment of snoring.
AB  - CONCLUSIONS: The safety of treatment with palatal implants remains high 3 years
      after the procedure. The implant extrusion rate decreases over time. Additional
      surgery to the palate is safe. The presence of the implants seems important in
      sustaining efficacy past 1 year. OBJECTIVES: To investigate long-term safety and
      treatment results of palatal implants for treatment of snoring. METHODS: A
      prospective clinical non-randomized trial of 55 patients with primary snoring
      followed over a period of 3 years. RESULTS: No major adverse events were
      observed. Eleven of the 55 patients (20%) experienced implant extrusions, 8
      during the first year, 3 in the second, and none in the third year. Twenty-six
      patients (47.3%) had additional procedures past 1 year. Only one post-implant
      surgery caused an extrusion. The success defined as no additional surgery
      followed by endpoint satisfaction rate was 34.6%. For patients with implants
      intact it was 41.5% (17/41) at 3 years, significantly better than for those who
      experienced loss of implants.

PMID- 21905793
TI  - Effect of fibrin-coated collagen fleece (TachoComb) on pain and bleeding after
      adenotonsillectomy in children.
AB  - CONCLUSION: Even though the use of TachoComb does not decrease pain after
      tonsillectomy, it is safe and useful to reduce bleeding after tonsillectomy.
      OBJECTIVES: Sealing the post-tonsillectomy wound would be expected to reduce pain
      and bleeding by decreasing the exposure of the traumatized tissue and sensory
      nerves. TachoComb is a powerful topical hemostatic agent. The objectives of this
      study were to evaluate the effect of TachoComb on reduction of pain and bleeding
      after tonsillectomy. METHODS: A prospective randomized double-blind study was
      performed on 120 pediatric patients undergoing adenotonsillectomy. The patients
      were randomized into two groups: use/non-use of TachoComb. In the study group,
      each tonsillar bed was covered with a TachoComb strip at the end of operation. No
      hemostatic agents were used in the control group. After surgery, patients were
      monitored for pain, bleeding, oral intake, medication administration, activity,
      and complications using a 10-day diary. RESULTS: In all, 110 patients returned
      and filled in the diary. The use of TachoComb did not decrease pain, reduce the
      use of analgesic drugs or speed recovery to normal everyday life. Post-surgery
      bleeding was not experienced by any of the TachoComb patients, but occurred in
      five of the control patients. The result had borderline statistical significance
      (p < 0.1).

PMID- 21905794
TI  - Solitary fibrous tumor of the petrous bone: a successful treatment option.
AB  - The patient was a 48-year-old man complaining about right hemicranial pain and
      deafness of 1 year's duration. MRI showed a solid well-vascularized mass
      destroying the mastoid and petrous bone, and with an epidural component that
      pulled the right cerebellar hemisphere. The patient underwent a right modified
      type A infratemporal approach, which allowed complete resection of the tumor,
      with a low morbidity. The pathological diagnosis was solitary fibrous tumor. The
      patient received complementary treatment with radiotherapy. At 24 months after
      the initial treatment the patient is free of disease. We conclude that solitary
      fibrous tumor of the petrous bone can be satisfactorily treated with surgical
      excision followed by radiotherapy, with low morbidity and excellent facial
      function. To our knowledge this is the first description of a solitary fibrous
      tumor of the petrous bone. Due to the lack of consensus in treating rare tumors,
      we want to offer this management approach for treating this kind of tumor.

PMID- 21905795
TI  - Diagnosis of the subtype and affected ear of benign paroxysmal positional vertigo
      using a questionnaire.
AB  - CONCLUSION: The prediction of subtype and the affected ear of benign paroxysmal
      positional vertigo (BPPV) derived from the answers to our questionnaire can
      support the definitive diagnosis of BPPV. OBJECTIVES: We examined to what extent
      the diagnosis of subtype and the affected ear of BPPV judged from answers to a
      questionnaire agreed with the diagnosis decided by the results of the positional
      nystagmus test. METHODS: We asked the following questions: 'What kind of head
      movements induce vertigo?' and 'How long does the vertigo continue?'. As for the
      affected ear, we asked which ear was lower during stronger vertigo when induced
      in a supine position or during sleep. RESULTS: The percentages of correct
      diagnosis speculated by the combined answers were 69% in posterior canal-type
      BPPV, 48% in BPPV with geotropic nystagmus, and 39% in BPPV with apogeotropic
      nystagmus. The percentage of correct diagnoses of the affected ear was more than
      80%.

PMID- 21905796
TI  - Aggressive course of multiple de novo cavernous malformations.
AB  - The risk of hemorrhage from an intracerebral cavernous malformation has been
      estimated at 2%-4% per year. In patients with multiple cavernous malformations,
      typically there are 1 or 2 dominant lesions that result in symptoms. This report
      highlights an unusual case of recurrent hemorrhage from de novo cavernous
      malformations.   This 35-year-old man had a generalized seizure in 2007. Magnetic
      resonance imaging performed at the time showed multiple hemorrhagic lesions
      suggestive of cavernous malformations. Two years later, the patient had clinical
      symptoms referable to a midbrain hemorrhage. This lesion was not present on 2007
      standard and gradient echo images. One year later, the patient had another
      clinical hemorrhage at the cervical medullary junction. This lesion was also not
      present on earlier imaging. Genetic testing was negative for the known familial
      types of cavernous malformation. A lesion was biopsied to ensure correct
      diagnosis, and the results were pathologically consistent with a cavernous
      malformation. The patient had a fourth clinical hemorrhage in 2011 from a
      separate lesion. All hemorrhage symptoms were mild, and he returned to normal
      functioning and work after each hemorrhage.   This case highlights several
      unusual features of the known natural history of intracerebral cavernous
      malformations. In this case, resection of the hemorrhagic lesion would not have
      altered future hemorrhage risk since each new hemorrhage was from a de novo
      lesion.

PMID- 21905797
TI  - Functional neurosurgery and hemorrhage.

PMID- 21905798
TI  - Reducing hemorrhagic complications in functional neurosurgery: a large case
      series and systematic literature review.
AB  - OBJECT: Hemorrhagic complications carry by far the highest risk of devastating
      neurological outcome in functional neurosurgery. Literature published over the
      past 10 years suggests that hemorrhage, although relatively rare, remains a
      significant problem. Estimating the true incidence of and risk factors for
      hemorrhage in functional neurosurgery is a challenging issue. METHODS: The
      authors analyzed the hemorrhage rate in a consecutive series of 214 patients
      undergoing image-guided deep brain stimulation (DBS) lead placement without
      microelectrode recording (MER) and with routine postoperative MR imaging lead
      verification. They also conducted a systematic review of the literature on
      stereotactic ablative surgery and DBS over a 10-year period to determine the
      incidence and risk factors for hemorrhage as a complication of functional
      neurosurgery. RESULTS: The total incidence of hemorrhage in our series of image
      guided DBS was 0.9%: asymptomatic in 0.5%, symptomatic in 0.5%, and causing
      permanent deficit in 0.0% of patients. Weighted means calculated from the
      literature review suggest that the overall incidence of hemorrhage in functional
      neurosurgery is 5.0%, with asymptomatic hemorrhage occurring in 1.9% of patients,
      symptomatic hemorrhage in 2.1% and hemorrhage resulting in permanent deficit or
      death in 1.1%. Hypertension and age were the most important patient-related
      factors associated with an increased risk of hemorrhage. Risk factors related to
      surgical technique included use of MER, number of MER penetrations, as well as
      sulcal or ventricular involvement by the trajectory. The incidence of hemorrhage
      in studies adopting an image-guided and image-verified approach without MER was
      significantly lower than that reported with other operative techniques (p < 0.001
      for total number of hemorrhages, p < 0.001 for asymptomatic hemorrhage, p < 0.004
      for symptomatic hemorrhage, and p = 0.001 for hemorrhage leading to permanent
      deficit; Fisher exact test). CONCLUSIONS: Age and a history of hypertension are
      associated with an increased risk of hemorrhage in functional neurosurgery.
      Surgical factors that increase the risk of hemorrhage include the use of MER and
      sulcal or ventricular incursion. The meticulous use of neuroimaging-both in
      planning the trajectory and for target verification-can avoid all of these
      surgery-related risk factors and appears to carry a significantly lower risk of
      hemorrhage and associated permanent deficit.

PMID- 21905799
TI  - Subthalamic nucleus stimulation for attenuation of pain related to Parkinson
      disease.
AB  - OBJECT: The objective of this study was to evaluate the efficacy of chronic
      subthalamic nucleus (STN) stimulation for alleviating pain related to Parkinson
      disease (PD). METHODS: Among 163 consecutive patients undergoing STN stimulation,
      69 were identified as experiencing pain preoperatively that was related to their
      PD. All 69 patients suffering from pain were followed up prospectively for 12
      months after surgery. All patients described the severity of their pain according
      to a visual analog scale (VAS) preoperatively and at 2 weeks, 6 months, and 12
      months postoperatively. Pain unrelated to PD was not studied. RESULTS: Several
      types of pain related to PD, the categories of which were based on a modification
      of 2 previous classifications (Ford and Honey), can occur in such patients: 1)
      musculoskeletal pain, 2) dystonic pain, 3) somatic pain exacerbated by PD, 4)
      radicular/peripheral neuropathic pain, and 5) central pain. The overall mean VAS
      score was significantly decreased postoperatively by 75% and 69% at 2 weeks and 6
      months, respectively (p < 0.001). The mean VAS score at 12 months was also
      decreased by 80%, but 6 instances of pain (3 reports of somatic back pain and 3
      reports of radicular/peripheral neuropathic pain) required additional spinal
      surgery to alleviate the pain severity. The results were analyzed using the
      Wilcoxon signed-rank test and demonstrated a significant reduction in VAS scores
      at all follow-up assessments (p < 0.001). Musculoskeletal pain and dystonic pain
      were well alleviated by STN stimulation. In contrast, somatic pain exacerbated by
      PD and peripheral neuropathic pain originating from lumbar spinal diseases, such
      as spondylosis deformans and/or canal stenosis, often deteriorated
      postoperatively despite attenuation of the patients' motor disability. Patients
      with central pain were poor responders. CONCLUSIONS: This study found that STN
      stimulation produced significant improvement of overall pain related to PD in
      patients with advanced PD, and the efficacy continued for at least 1 year. The
      present results indicate that musculoskeletal pain and dystonic pain responded
      well to STN stimulation, but patients with back pain (somatic pain) and
      radicular/peripheral neuropathic pain originating from spinal disease have a
      potential risk for postoperative deterioration of their pain.

PMID- 21905800
TI  - Neurocognitive function before and after surgery for insular gliomas.
AB  - OBJECT: Insular gliomas can be resected with acceptable rates of neurological
      morbidity, but little is known with regard to impairment of higher-order
      neurocognitive functions. The frequency and functional impact of neurocognitive
      deficits in patients with gliomas has until recently been underappreciated. The
      authors therefore examined neurocognitive function in patients with insular
      gliomas and compared the findings in this group to those in a matched control
      group of patients with gliomas in nearby brain regions. METHODS: Thirty-three
      patients with WHO Grade II or III insular gliomas participated in
      neuropsychological evaluations before and after resection. To establish whether
      the pattern of neurocognitive performance was different from that of other
      patients with tumors in neighboring areas, patients with insular tumors were
      matched with control patients for age, educational level, preoperative Karnofsky
      Performance Scale score, tumor side, grade, and volume. The control group
      comprised patients in whom gliomas had been resected from frontal, temporal, and
      parietal areas near the insula. Baseline pre- and postoperative neurocognitive
      test results were compared between and within groups. RESULTS: Preoperative
      neurocognitive impairment was common in both insular and control groups. Patients
      with insular tumors had significantly worse preoperative performance on naming
      tests. In both groups, postoperative decline occurred in most neurocognitive
      domains. There were no statistically significant differences between patients in
      the insular and control groups with regard to rates of postoperative decline on
      any test. However, there were trends suggesting differential cognitive
      performance postoperatively, because patients with insular tumors were more
      likely to experience greater decline in learning and memory. Neurological
      morbidity was similar to prior rates reported in the literature. CONCLUSIONS: Few
      statistically significant differences in cognitive function were observed between
      patients in the insular and control groups at either the pre- or postoperative
      evaluation, although there was a trend for patients with insular tumors to
      exhibit greater postoperative decline in learning and memory. Although
      technically more challenging, surgery for insular region glioma appears feasible
      without profound neurological or cognitive morbidity for many patients.

PMID- 21905801
TI  - Communicating hydrocephalus following surgery and adjuvant radiochemotherapy for
      glioblastoma.
AB  - OBJECT: Communicating hydrocephalus is an uncommon complication in patients
      treated for glioblastoma multiforme (GBM). Its pathogenesis remains unclear. The
      authors evaluated the clinical and radiological factors associated with the onset
      of communicating hydrocephalus and the impact of ventriculoperitoneal (VP) shunt
      surgery on the outcome of these patients. METHODS: One hundred twenty-four
      patients harboring GBM, who had undergone craniotomy for tumor resection and
      adjuvant radiochemotherapy, were retrospectively assessed. Seven of them
      developed communicating hydrocephalus and were treated with VP shunt surgery.
      Clinical and radiological estimates included Karnofsky Performance Scale (KPS)
      score, previous surgery, overall survival (OS), CSF pressure and components,
      tumor location, and leptomeningeal dissemination. RESULTS: All 7 patients who
      developed communicating hydrocephalus had undergone at least 2 craniotomies for
      tumor resection before the onset of hydrocephalus (p = 0.0006; Fisher exact
      test). Six cases showed high levels of CSF proteins. There was a highly
      significant relationship between ventricular opening at surgery for tumor
      recurrence and onset of hydrocephalus (p = 0.0002; Fisher exact test). In these
      patients, VP shunt surgery was followed by a significant improvement of KPS score
      (p = 0.0180; Wilcoxon signed-rank test). The median OS after VP shunt insertion
      was 5 +/- 2.9 months. CONCLUSIONS: Ventricular opening after radiochemotherapy
      and high CSF protein levels are significant predictors of communicating
      hydrocephalus in patients with GBM. The VP shunt surgery improves quality of life
      in these patients.

PMID- 21905802
TI  - Convergent validity of the Mullen Scales of Early Learning and the differential
      ability scales in children with autism spectrum disorders.
AB  - Despite widespread use of the Mullen Scales of Early Learning (MSEL; E. M.
      Mullen, 1995 ) as a cognitive test for children with autism spectrum disorders
      and other developmental disabilities, the instrument has not been independently
      validated for use in these populations. Convergent validity of the MSEL and the
      Differential Ability Scales (DAS; C. D. Elliott, 1990 , 2007 ) was examined in 53
      children with autism spectrum disorder and 19 children with nonspectrum
      diagnoses. Results showed good convergent validity with respect to nonverbal IQ
      (NVIQ), verbal IQ (VIQ), and NVIQ-VIQ profiles. These findings provide
      preliminary support for the practice of using MSEL age-equivalents to generate
      NVIQ and VIQ scores. Establishing convergent validity of cognitive tests is
      needed before IQs derived from different tests can be conceptualized as a uniform
      construct.

PMID- 21905803
TI  - Functional magnetic resonance imaging of cognitive processing in young adults
      with Down syndrome.
AB  - The authors used functional magnetic resonance imaging (fMRI) to investigate
      neural activation during a semantic-classification/object-recognition task in 13
      persons with Down syndrome and 12 typically developing control participants (age
      range  =  12-26 years). A comparison between groups suggested atypical patterns
      of brain activation for the individuals with Down syndrome. Correlation analyses
      between an index of visual spatial ability and brain activation depicted a
      positive relationship between (a) this index and brain activation in regions of
      the occipital and parietal lobes for the typically developing individuals and (b)
      the middle and dorsal frontal gyri in the individuals with Down syndrome. These
      findings supported the authors' hypothesis that persons with Down syndrome
      demonstrate atypical neural activation compared with typically developing
      individuals matched for chronological age.

PMID- 21905804
TI  - Effect of incorporating adaptive functioning scores on the prevalence of
      intellectual disability.
AB  - Surveillance and epidemiologic research on intellectual disability often do not
      incorporate adaptive functioning (AF) data. Exclusion of AF data leads to
      overestimation of the prevalence of intellectual disability, the extent of which
      is not known. In this study, the authors evaluated the effect of incorporating AF
      data on overall intellectual disability prevalence according to sociodemographic,
      economic, and severity characteristics. Between 2002 and 2006, the Metropolitan
      Atlanta Developmental Disabilities Surveillance Program identified 1,595 8-year
      old children who met the study's intellectual disability surveillance-case
      definition of IQ <= 70. AF scores were not available for 9.2% of the case
      children, specifically those with mild intellectual disability and low
      socioeconomic backgrounds. Prevalence estimates showed few substantive changes
      when incorporating AF data. The authors conclude that use of IQ data alone
      appears to be appropriate for measuring population intellectual disability
      prevalence.

PMID- 21905805
TI  - Chronic disease risks in young adults with autism spectrum disorder: forewarned
      is forearmed.
AB  - An emerging, cost-effective method to examine prevalent and future health risks
      of persons with disabilities is electronic health record (EHR) analysis. As an
      example, a case-control EHR analysis of adults with autism spectrum disorder
      receiving primary care through the Cleveland Clinic from 2005 to 2008 identified
      108 adults with autism spectrum disorder. In this cohort, rates of chronic
      disease included 34.9% for obesity, 31.5% for hyperlipidemia, and 19.4% for
      hypertension. Compared with a control cohort of patients from the same health
      system matched for age, sex, race, and health insurance status, adults with
      autism spectrum disorder were more likely to be diagnosed with hyperlipidemia
      (odds ratio  =  2.0, confidence interval  =  1.2-3.4, p  =  .012). Without
      intervention, adults with autism spectrum disorder appear to be at significant
      risk for developing diabetes, coronary heart disease, and cancer by midlife.

PMID- 21905808
TI  - Fourth Scandinavian Pediatric Obesity Conference (SPOC). Foreword.

PMID- 21905806
TI  - Changes in maladaptive behaviors from midchildhood to young adulthood in autism
      spectrum disorder.
AB  - The current study prospectively examined trajectories of change in symptoms of
      irritability, hyperactivity, and social withdrawal, as well as predictors of such
      behaviors, for ages 9-18 years for youths with autism spectrum disorder and a
      comparison group with nonspectrum developmental delays. Children with more severe
      core features of autism had consistently higher irritability and hyperactivity
      scores over time than those with broader autism spectrum disorder and nonspectrum
      delays. Across all diagnoses, behaviors related to hyperactivity showed the
      greatest improvement. Social withdrawal worsened with age for a substantial
      proportion of youths with autism spectrum disorder but not for the nonspectrum
      comparison group. Compared with youths without autism spectrum disorder, children
      with the disorder showed greater heterogeneity in trajectories for maladaptive
      behaviors.

PMID- 21905809
TI  - Human adenovirus-36 and childhood obesity.
AB  - There is increasing evidence that obesity in humans is associated with infection
      with human adenovirus-36 (Adv36). Infection of experimental animals with Adv36
      demonstrates that this virus causes obesity. Human studies have shown a
      prevalence of Adv36 infection of 30% or greater in obese adult humans, but a
      correlation with obesity has not always been demonstrated. In contrast, three
      published studies and one presented study with a total of 559 children all show
      that there is an increase in prevalence of Adv36 infection in obese children
      (28%) compared to non-obese children (10%). The explanation for the apparently
      more robust correlation of Adv36 infection with obesity in children vs. adults is
      not clear. The data in animals and people suggests that Adv36 has contributed to
      the worldwide increase in childhood obesity. More research is needed to identify
      prevalences and consequences of Adv36 infection in people of all age groups and
      geographic locations.

PMID- 21905810
TI  - The role of nutrient partitioning and stem cell differentiation in pediatric
      obesity: a new theory.
AB  - It is commonly theorized that some youths become fatter than others simply
      because they eat too much and exercise too little; i.e., they have an excessive
      positive energy balance. This theory suggests that obesity prevention efforts
      should emphasize dietary strategies designed to reduce energy intake, with
      moderate physical activity (PA) playing a supporting role. However, such
      interventions have typically been unsuccessful, perhaps because pediatric
      research that has measured body fatness, rather than weight, has found that the
      simple energy balance theory is faulty; it is critical to also consider whether
      the ingested energy is deposited in fat or lean tissue in order to provide a more
      complete picture of the etiology of pediatric obesity. In some way that is still
      poorly understood; vigorous PA and mechanical stimulation of the body stimulate
      stem cells to differentiate into bone and muscle rather than fat, with the result
      that ingested nutrients tend to be partitioned into lean tissue rather than fat.
      Thus, active youths tend to ingest more energy than their sedentary peers without
      increasing the percentage of the body mass that is comprised of fat tissue.
      Having a high level of both energy expenditure and intake is in accord with the
      biologic drives of youths because it encourages them to ingest sufficient amounts
      of the nutrients needed for healthy growth. Thus, public health interventions are
      likely to be more effective if they devote more attention to increasing PA and
      less attention to dietary strategies designed to reduce energy intake.

PMID- 21905811
TI  - Is adipose tissue metabolically different at different sites?
AB  - This review focuses on metabolic differences of adipose tissue at different sites
      of the body, with emphasis in pediatrics. Adipose tissue is composed of various
      cell types, which include adipocytes and other cells of the stromal vascular
      fraction such as preadipocytes, blood cells, endothelial cells and macrophages.
      Mammals have two main types of adipose tissue: white adipose tissue (WAT), and
      brown adipose tissue (BAT), each of which possesses unique cell autonomous
      properties. WAT and BAT differ at the functional, as well as the morphological
      and molecular levels. WAT accumulates surplus energy mainly in the form of
      triacylglycerols and BAT dissipates energy directly as heat. Recently, functional
      BAT in humans has been located in the neck, supraclavicular, mediastinal and
      interscapular areas. WAT is distributed throughout the body in the form of two
      major types: subcutaneous adipose tissue (SWAT) and the intra-abdominal visceral
      adipose tissue (VWAT). VWAT tissue is associated with insulin resistance,
      diabetes mellitus, dyslipidaemia, hypertension, atherosclerosis, hepatic
      steatosis, and overall mortality whereas SWAT and BAT have intrinsic beneficial
      metabolic properties. Subcutaneous and visceral adipocytes derive from different
      progenitor cells that exhibit a different gene expression pattern. SWAT responds
      better to the antilipolytic effects of insulin and other hormones, secrets more
      adiponectin and less inflammatory cytokines, and is differentially affected by
      molecules involved in signal transduction as well as drugs compared with VWAT.
      Current research is investigating various approaches of BAT and SWAT
      transplantation, including new sources of adipocyte progenitors. This may be
      important for the potential treatment of childhood obesity.

PMID- 21905812
TI  - Stress and obesity/metabolic syndrome in childhood and adolescence.
AB  - Chronic distress contributes to the development of obesity and comorbid states.
      Stress is the disturbance of the complex dynamic equilibrium that all organisms
      must maintain, and is associated with activation of the Stress system comprising
      of the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous
      systems. The stress system functions in a baseline circadian fashion and
      interacts with other systems of the organism to regulate a variety of behavioral,
      endocrine, metabolic, immune and cardiovascular functions. The experience of
      perceived or real uncontrollable intense and/or chronic stress (distress) may
      lead to several psychopathologic conditions, including anxiety, depressive and
      psychosomatic disorders, substance abuse, obesity and the metabolic syndrome, and
      osteoporosis, as well as impaired reproductive and immune functions. Developing
      children and adolescents are particularly vulnerable to the effects of chronic
      stress. Both behavioral and biological pathways are involved in the connection
      between chronic stress and obesity in adults and children. Emotional "comfort"
      eating, lack of sleep, impulsive behaviours and selection of specific foods often
      characterize stressed individuals. In addition to specific behaviours,
      dysregulation of the stress system through increased secretion of cortisol and
      catecholamines, especially in the evening hours, and in concert with concurrently
      elevated insulin concentrations, leads to development of central obesity, insulin
      resistance and the metabolic syndrome. In children, chronic alterations in
      cortisol secretion may have additional effects on cognitive and emotional
      development, timing of puberty and final stature. Obese children and adolescents
      are frequently entangled in a vicious cycle between distress, impairing self
      image and distorted self-image, maintaining and worsening distress.

PMID- 21905813
TI  - The association between physical activity, physical fitness and development of
      metabolic disorders.
AB  - BACKGROUND: Cardiovascular (CVD) risk factors have been shown to cluster in some
      children. This has been shown in children from the age of nine years, but
      recently we found no clustering in six-year old children. It is uncertain when
      clustering develops and which parameters are related to the development of
      clustered CVD risk. METHODS: A longitudinal study including 484 children aged six
      years. Three years later, 434 children participated in a follow-up. The main
      outcome was clustering of five CVD risk factors: homeostasis assessment insulin
      resistance (HOMA), total cholesterol:HDL ratio, triglyceride (TG), systolic blood
      pressure and sum of four skinfolds. Independent variables were physical activity
      and cardiorespiratory fitness. RESULTS: CVD risk factors were independently
      distributed in the six-year-olds, and there was no association between composite
      risk factor score and physical fitness or activity even if there were obese and
      unfit children in the population. Clustering of CVD risk factors was found at the
      age of nine years, and the observed number with three or more CVD risk factors
      was 3.33 (95% CI: 1.41-7.87) times higher than expected if risk factors had been
      independently distributed. At the age of nine years, the lowest quartile of
      fitness had 34.9 (95% CI: 8.0-152.5) times higher risk of having clustered risk
      than the most fit quartile. CONCLUSION: Clustering of CVD risk factors developed
      between the age of six and nine years. At nine years of age clustered CVD risk
      was highly associated with low fitness level.

PMID- 21905814
TI  - How to make overweight children exercise and follow the recommendations.
AB  - As regular physical activity of high enough intensity is essential in the
      management of overweight, efforts should be made to increase physical activity
      adherence in overweight children. To make overweight children exercise and follow
      the recommendations, it is essential to have insight into determinants of
      exercise initiation and adherence. According to the Self-determination Theory,
      creating opportunities to satisfy the need for autonomy (i.e., having choices),
      competence (i.e., feeling effective) and relatedness (i.e., being socially
      connected) might increase autonomous motivation for physical activity in
      overweight children and promote a long-lasting active lifestyle. To increase
      feelings of autonomy in overweight children, exercise programs could be delivered
      in an autonomy-supportive manner by providing choices, supporting the child's
      initiatives, avoiding use of external rewards, offering relevant information and
      rationale for changing behaviour, making a decisional balance and using autonomy
      supportive language, while minimizing pressure and control. Perceived competence
      in physical activities could be increased by offering activities tailored to the
      capabilities of the overweight child, helping the children set realistic goals,
      learning the children self-management skills, providing the children with
      appropriate feedback and organizing separate exercise sessions for overweight
      children. Feelings of relatedness in overweight children might increase by
      adopting an empathic approach, showing interest in the child's well-being and
      problems, showing enjoyment and enthusiasm, knowing the names of the children,
      talking to the children as equals, offering group sessions and talks, encouraging
      club participation and having a sports partner and encouraging parental support.

PMID- 21905816
TI  - Intima media thickness-related risk factors in childhood obesity.
AB  - Macroangiopathy caused by atherosclerosis is one of the major morbidity and
      mortality factors in obese adults with dyslipidemia, hypertension and disturbed
      glucose metabolism. However, the onset of these cardiovascular changes is not
      well established. Measuring the intima- media thickness (IMT) of the common
      carotid artery, as a non-invasive marker for early atherosclerotic changes, has
      been reported to be reliable and predictive for later cardiovascular disease.
      Increased IMT has been reported in children with diabetes mellitus type 1 and 2.
      IMT was related to both hyperglycaemia and dyslipidemia in these children.
      Furthermore, children with hypertension demonstrated increased IMT. Moreover,
      children with familial hypercholesterolemia have higher IMT values as compared to
      healthy children. Obese children with the features of the metabolic syndrome
      (MetS) such as hypertension, dyslipidemia, or impaired glucose tolerance also
      demonstrated increased IMT. A strong association between IMT and parameters of
      the MetS has been reported for impaired glucose tolerance. Furthermore, increased
      androgens in girls with polycystic ovarian syndrome (PCOS) are associated with
      increased IMT measurements. Reduction of overweight and normalization of blood
      pressure, glucose metabolism and dyslipidemia were associated with a reduction of
      IMT in children and adolescents. In conclusion, early vascular changes already
      occur in obese children with MetS suggesting that rather cardiovascular risk
      factors such as hypertension, dyslipidaemia, or disturbed glucose metabolism are
      associated to increased IMT than obesity per se. Most importantly, these early
      changes are reversible if effective therapy of cardiovascular risk factors could
      be achieved.

PMID- 21905815
TI  - From fatness to leaness: where did we go wrong?
AB  - INTRODUCTION: In humans, using adipose tissue to store fat represents the most
      effective means to 'store' energy. On the whole and over an extended period of
      time, intake of energy has exceeded energy expenditure and where previously the
      excess of energy was regularly turned over through physical activity, this
      crucial circle has now been broken. In this way obesity ascribed to either
      'overeating' or 'under-activity'. Central adiposity poses a major risk for
      chronic diseases such as hypertension, cardiovascular diseases and diabetes, and
      possibly mortality. Predictors and potential factors underlying the development
      of excess adiposity were well studied and established with emphasis on fat mass.
      OBJECTIVE: When studying the development of body composition, bone mass, fat mass
      and lean mass should be considered together. The purposes of the present paper
      are to briefly analyze the methodologies used to estimate the lean mass (LM),
      understanding the interrelationship between fat mass (FM) and LM and underline
      the importance of LM during growth. RESULTS: As muscle and adipose tissue are
      closely linked anatomically, biologically and pathologically, the
      interrelationship between these two tissues is of great importance in
      understanding the pathogenesis and development of diseases related to obesity and
      physical activity/inactivity. LM estimation, and LM programming could show
      several implications for the early origin of obesity. CONCLUSION: Measurements of
      lean mass may improve the capacity to tailor nutrition, treatment and management
      to metabolic criteria. This approach could offer a unique opportunity of putting
      lean mass in the first line keeping in mind that this metabolic active tissue
      need to be preserved when obesity prevention and treatment are considered.

PMID- 21905817
TI  - Does obesity lead to a specific lipid disorder? Analysis from the
      German/Austrian/Swiss APV registry.
AB  - Overweight and obese youth represent a challenge for the affected individual, the
      healthcare system as well as society as a whole. Increased long-term
      cardiovascular risk is one of the major consequences of early-onset obesity,
      affecting both life expectancy and quality of life. The aim of this report is to
      study the effects of age, gender and obesity category on the presence of
      individual components of dyslipidemia using normal-weight subjects from the
      population-based German KIGGS study including 17,641 randomly selected children
      and adolescents, aged 0-18 years (11,110 normal-weight subjects with lipid
      measurements) and the German-Austrian-Swiss APV registry, including 57,239
      overweight or obese children, adolescents and young adults from 162 specialized
      obesity care centers (lipid measurements available in 29,711 subjects). Subjects
      were classified according to BMI category based on the age- and gender-adjusted
      BMI-z-scores as recommended by the AGA (German Pediatric Obesity working group).
      Cut-offs for dyslipidemia were based on the recommendations by the American Heart
      Association: total cholesterol: > 5.2 mmol/l, HDL-cholesterol < 0.9 mmol/l, LDL
      cholesterol > 3.4 mmol/l, triglycerides > 1.7 mmol/l. Using SAS 9.2-software,
      hierarchic modeling with both linear and logistic regression analysis was
      applied. Within the group of normal-weight children, fasting triglycerides were
      elevated in 3.3%, LDL-cholesterol in 7.2% and HDL-cholesterol was reduced in
      3.1%. With increasing BMI-category, the prevalence of hypertriglyceridemia and
      reduced HDL-cholesterol increased rapidly. A weaker relationship was present for
      LDL-cholesterol and total cholesterol. Among obese youth, 30.5% displayed any
      dyslipidemia, underlining the importance of adequate screening and intervention.

PMID- 21905818
TI  - Fatty liver disease in obese children--relation to other metabolic risk factors.
AB  - Liver steatosis, known as non-alcoholic fatty liver disease (NAFLD) is common
      among obese children. Deposition of lipid within the liver represents part of an
      abnormal lipid partitioning pattern, most commonly associated with increased
      intra-abdominal fat. Lipid deposition in the liver can be a cause of peripheral
      insulin resistance via local acceleration of lipogenesis and a cause of hepatic
      insulin resistance leading to further compensatory hyperinsulinemia. The typical
      obese child with NAFLD will usually manifest other components of the insulin
      resistance syndrome such as dyslipidemia, hypertension and altered glucose
      metabolism. As liver steatosis itself is usually asymptomatic, a high index of
      suspicion for its presence should be present in obese insulin resistant youth who
      present with dyslipidemia or altered glucose metabolism or manifest anamnestic or
      physical signs that suggest the presence of insulin resistance.

PMID- 21905819
TI  - Bariatric surgery in morbidly obese adolescents: long-term follow-up.
AB  - OBJECTIVE: Morbid obesity is an increasingly common disease in the industrialized
      world and poses a great challenge to the medical community. Many obese
      adolescents have undergone various conservative treatment methods without
      adequate success so that a surgical approach became necessary. We report on 18
      patients who underwent bariatric surgery as well as a long-term follow-up
      program. METHODS: Eight patients received a laparoscopic adjustable gastric
      banding (LAGB). Four of these had to undergo a gastric bypass surgery (GByp) as
      second procedure due to insufficient weight loss. Nine patients primarily
      received a gastric bypass. RESULTS: LAGB: Mean weight loss after 24 months was 20
      +/- 6.3 kg. Four of the patients showed a regain in weight leading to a mean
      weight loss of 9 kg compared to initial weight after 53.3 months mean in this
      group. These patients had to undergo an additional gastric bypass procedure and
      lost 31 +/- 18.3 kg after 18 months. GByp: Mean weight loss in nine patients
      after gastric bypass (primary procedure) was 31 +/- 10.2 kg after 12 months and
      36 +/- 30.1 kg at the end of the observation time. Sleeve: Initial weight in this
      patient was 232 kg with a weight loss of 38 kg after 24 months. DISCUSSION AND
      CONCLUSION: It is remarkable that in four of eight patients who underwent LAGB
      had to undergo a second surgical procedure (GByp). No previous indicator, neither
      from a psychological nor from a medical point of view, could be detected. More
      long-term studies including psychological aspects seem to be necessary.

PMID- 21905820
TI  - Which psychological method is most effective for group treatment?
AB  - While outcome studies in pediatric obesity have received considerable attention,
      research on different components of effective interventions remains limited.
      Little is known which psychological method (i.e., behavior modification,
      cognitive behavior therapy and family therapy) is most useful or how the choice
      of program delivery (group/individual) influences the intervention outcomes.
      Group treatment is of particular interest for two reasons. First, motivation is
      important for behavior change; in group settings motivation can be increased in
      two ways: by the group leader and through the interaction with the group
      participants. Second, group treatment can be more cost-effective than individual
      approaches (i.e., it requires fewer staff resources and space). This paper aims
      to comment on the influence of the method choice and delivery in pediatric
      obesity interventions through discussion of the existing evidence on current
      programs. In addition, two examples of useful models will be described in more
      detail: the Yale Bright Bodies Weight Management Program and the Family Weight
      School. These are outpatients programs both targeting families with severely
      obese children but through different methodological approaches. Finally,
      directions for future research will be explored, particularly regarding how the
      selection of program delivery and psychological method affect treatment outcomes
      in various populations.

PMID- 21905821
TI  - Managing obesity--from childhood and onwards.
AB  - It is unclear whether the obesity epidemic has come to a halt. Perhaps the
      incidence is declining, at least in pre-school children. However, the obesity
      rate is higher than ever before. Prevention is a priority, especially in
      children, but has not been very successful to date. Treatment has basically
      offered the same tools for decades. The recent development of obesity
      pharmacotherapy has regressed with--in most countries--only one drug of modest
      effect available. Bariatric surgery has therefore been considered one of the few
      solutions in the adult setting and is gaining increasing attention as a treatment
      option, even in pediatric extreme obesity. In some countries, government action
      for prevention has been taken, but too often resources have not been set aside.
      This review addresses new and old strategies to manage obesity--from childhood
      and onwards.

PMID- 21905822
TI  - Thujone inhibits lung metastasis induced by    B16F-10 melanoma cells in C57BL/6
      mice.
AB  - The antimetastatic potential of thujone, a naturally occurring monoterpene, was
      evaluated. Metastasis was induced in C57BL/6 mice by injecting highly metastatic
      B16F-10 melanoma cells through the lateral tail vein. Administration of thujone
      (1 mg.(kg body weight)(-1)), prophylactically and simultaneously with tumor
      induction, inhibited tumor nodule formation in the lungs by 59.45% and 57.54%,
      respectively, with an increase in the survival rate (33.67% and 32.16%) of the
      metastatic tumor bearing animals. These results correlated with biochemical
      parameters such as lung collagen hydroxyproline, hexosamine and uronic acid
      contents, serum sialic acid and gamma-glutamyl transpeptidase levels, and
      histopathological analysis. Treatment with thujone downregulated the production
      of proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin
      (IL)-1beta, IL-6, and granulocyte-monocyte colony-stimulating factor. Thujone
      administration downregulated the expression of matrix metalloproteinase (MMP)-2,
      MMP-9, extracellular signal-regulated kinase (ERK)-1, ERK-2, and vascular
      endothelial growth factor (VEGF) and also upregulated the expression of nm-23,
      tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 in the lung tissue of
      metastasis-induced animals. Treatment with thujone inhibited the activity of MMP
      2 and MMP-9 in gelatin zymographic analysis. Thujone treatment significantly
      inhibited the invasion of B16F-10 melanoma cells across the collagen matrix in a
      Boyden chamber. Thujone also inhibited the adhesion of tumor cells to collagen
      coated microtire plate wells and the migration of B16F-10 melanoma cells across a
      polycarbonate filter in vitro. These results indicate that Thujone can inhibit
      the lung metastasis of B16F-10 cells through inhibition of tumor cell
      proliferation, adhesion, and invasion, as well as by regulating expression of
      MMPs, VEGF, ERK-1, ERK-2, TIMPs, nm23, and levels of proinflammatory cytokines
      and IL-2 in metastatic animals.

PMID- 21905823
TI  - Concentration- and time-dependent effects of enoxaparin on human adenocarcinomic
      epithelial cell line A549 proliferation in vitro.
AB  - Non-small cell lung cancer (NSCLC) is a major health problem. Surgery is the only
      potential curative treatment, in spite of the high recurrence and mortality
      rates. Low molecular weight heparins (LMWH) have been suggested to have a
      positive impact on the outcome of various cancers, mainly attributed to their
      anticoagulant properties; yet a direct antineoplastic effect has not been
      excluded. We thought to evaluate the direct effect of the LMWH enoxaparin on the
      human lung adenocarcinomic epithelial cell line A549 and to determine potential
      antiproliferative and antimetastatic effects that could guide future trials. A549
      cells were cultured with different concentrations of enoxaparin (1-30 U/mL). Cell
      counting was performed at 24, 48, and 72 h. Detection of c-Myc protein and CD44
      protein was performed by electrophoresis and Western blotting. Statistical
      analysis was performed using paired Student's t tests. Cell counts were decreased
      with increasing concentrations and time of exposure to enoxaparin. This
      corresponds to decreased expression of c-Myc and CD44. In conclusion, enoxaparin
      displayed a direct dose and exposure duration dependent suppressor effect on A549
      cell proliferation and the expression of both c-Myc and CD44 in vitro, suggesting
      reduced proliferative and metastatic potentials of these cells.

PMID- 21905824
TI  - Effect of resveratrol derivative BTM-0512 on high glucose-induced dysfunction of
      endothelial cells: role of SIRT1.
AB  - Hyperglycemia impairs the function of endothelial cells. Sirtuin 1 (SIRT1) is
      involved in regulating the function of endothelial cells. Resveratrol, a
      polyphenol found in many plant species, exerts protective effects on endothelial
      cells through activation of SIRT1. The aims of this work were to explore whether
      BTM-0512, a novel derivative of resveratrol, is able to exert beneficial effects
      on high glucose-induced dysfunction of endothelial cells through regulation of
      SIRT1. We found that high glucose significantly impaired the function of
      endothelial cells as shown by reduced tube formation, cell migration, and cell
      adhesion concomitantly with downregulation of mRNA expression of SIRT1 and
      vascular endothelial growth factor as well as increased tumor necrosis factor
      alpha release and reactive oxygen species production. These effects of high
      glucose were inhibited by pretreatment with BTM-0512. The beneficial effects of
      BTM-0512 on high glucose-induced cell dysfunction were abolished by splitomicin,
      a specific inhibitor of SIRT1. The regulatory effects of BTM-0512 on high glucose
      induced changes in vascular endothelial growth factor mRNA expression and tumor
      necrosis factor-alpha release were also abolished by splitomicin. The results
      suggest that BTM-0512 exerts beneficial effects on high glucose-induced
      endothelial cell dysfunction through regulation of the SIRT1 - reactive oxygen
      species - vascular endothelial growth factor - tumor necrosis factor-alpha
      pathway.

PMID- 21905825
TI  - Disability identity of leaders in the self-advocacy movement.
AB  - Life stories and perspectives of leaders in the self-advocacy movement were
      explored to enhance knowledge about disability identity formation. In-depth
      qualitative interviews were conducted with 13 leaders in the self-advocacy
      movement. Five major themes emerged: (a) resistance--claiming personhood and
      voice; (b) connection with disability community; (c) reclaiming disability and
      personal transformation; (d) interconnection with broader disability rights
      movement; and (e) bond with social justice and interdependency.

PMID- 21905826
TI  - "I'm supposed to be in charge": self-advocates' perspectives on their self
      determination support needs.
AB  - In this qualitative interview study, we explored the perceptions of adults with
      intellectual disability regarding interpersonal or social supports needed to
      express their own self-determination. Specifically, 10 adults, all members of a
      self-advocacy group, were asked to discuss their understanding of the term self
      determination and ways in which support staff have either supported or inhibited
      their self-determination. Ten themes characterizing supportive and impeding staff
      actions were identified. The need for greater exploration of environmental and
      social influences on self-determination is emphasized.

PMID- 21905827
TI  - Gendered service delivery: a masculine and feminine perspective on staff gender.
AB  - Despite acknowledgement that paid caregivers have a significant impact on the
      lives of people with intellectual disability, the subjective experience of staff
      gender is rarely considered in research. Qualitative data from a study on the
      sexual health needs of men and boys with intellectual disability is presented. We
      designed this study to determine what impact staff gender has on the sexual
      health needs of men and boys with intellectual disability. Findings suggest that
      although staff traverse the same geographies of care, they do it in uniquely
      gendered ways. Staff gender is an important consideration when dealing with
      sexual health matters and can enhance the type and quality of relationships
      between people with intellectual disability.

PMID- 21905830
TI  - Perske's list: false confessions from 75 persons with intellectual disability.

PMID- 21905831
TI  - Reflections on monitoring the implementation of court orders in class action
      lawsuits.

PMID- 21905832
TI  - How the shift to individualize supports gets stuck and the first step out of
      gridlock.

PMID- 21905833
TI  - Parental supports for parents with intellectual and developmental disabilities.

PMID- 21905834
TI  - Barriers to conducting research with community-dwelling adults who have
      intellectual disabilities.

PMID- 21905835
TI  - Supporting religion and spirituality to enhance quality of life of people with
      intellectual disability: a Jewish perspective.

PMID- 21905836
TI  - The times they are a changing: special olympics and the movement towards valued
      lives and inclusion.

PMID- 21905839
TI  - Validation of a multi-residue enzyme-linked immunosorbent assay for qualitative
      screening of corticosteroids in liver, urine and milk.
AB  - A rapid and sensitive enzyme-linked immunosorbent assay (ELISA) was applied for
      the qualitative screening analysis of dexamethasone, betamethasone, flumethasone,
      and prednisolone in milk and urine, and dexamethasone, flumethasone and
      prednisolone in liver samples at levels corresponding to the European Union
      maximum residue limit (MRL), or at required performance levels (RPLs) for
      substances for which there is no established MRL. Method validation was performed
      according to Commission Decision 2002/657/EC criteria established for qualitative
      screening methods. In this regard, the following parameters were determined:
      detection capability (CCbeta), specificity, limit of detection (LOD), limit of
      quantitation (LOQ), recovery, within-laboratory reproducibility, linearity and
      ruggedness. LODs were 0.2, 1.2 and 0.6 ug kg(-1) in milk, urine and liver
      samples, and LOQ values were 0.3, 1.2 and 1.4 ug kg(-1) in milk, urine and liver,
      respectively. Recoveries from spiked samples ranged from 68% to 131% for
      dexamethasone, from 57% to 120% for flumethasone, from 60% to 155% for
      betamethasone, and from 23% to 32% for prednisolone, with a coefficient of
      variation (CV) between 1.6% and 21.2%. The CCbeta value was below the MRL/RPL for
      all examined matrices. Moderate variations of some critical factors in the sample
      pre-treatment for liver and milk samples were deliberately introduced for
      ruggedness evaluation and did not result in any negative effects on
      corticosteroid detection. The proposed method is suitable for qualitative
      screening analysis of corticosteroids in the above-mentioned food in conformity
      with the current European Union performance requirements.

PMID- 21905841
TI  - Quantum-behaved particle swarm optimization: analysis of individual particle
      behavior and parameter selection.
AB  - Quantum-behaved particle swarm optimization (QPSO), motivated by concepts from
      quantum mechanics and particle swarm optimization (PSO), is a probabilistic
      optimization algorithm belonging to the bare-bones PSO family. Although it has
      been shown to perform well in finding the optimal solutions for many optimization
      problems, there has so far been little analysis on how it works in detail. This
      paper presents a comprehensive analysis of the QPSO algorithm. In the theoretical
      analysis, we analyze the behavior of a single particle in QPSO in terms of
      probability measure. Since the particle's behavior is influenced by the
      contraction-expansion (CE) coefficient, which is the most important parameter of
      the algorithm, the goal of the theoretical analysis is to find out the upper
      bound of the CE coefficient, within which the value of the CE coefficient
      selected can guarantee the convergence or boundedness of the particle's position.
      In the experimental analysis, the theoretical results are first validated by
      stochastic simulations for the particle's behavior. Then, based on the derived
      upper bound of the CE coefficient, we perform empirical studies on a suite of
      well-known benchmark functions to show how to control and select the value of the
      CE coefficient, in order to obtain generally good algorithmic performance in real
      world applications. Finally, a further performance comparison between QPSO and
      other variants of PSO on the benchmarks is made to show the efficiency of the
      QPSO algorithm with the proposed parameter control and selection methods.

PMID- 21905844
TI  - Notice of retraction: Analysis of azoospermia factor loci polymorphisms among
      Tunisian infertile men with varicocele.

PMID- 21905842
TI  - Risky business: the need for hypothesis-generating research.

PMID- 21905845
TI  - Biomechanical proof of barbed sutures for the efficacy of laparoscopic
      pyeloplasty.
AB  - BACKGROUND AND PURPOSE: The gold standard for management of adult ureteropelvic
      junction obstruction is laparoscopic dismembered pyeloplasty (LPP), described by
      Anderson-Hynes, with reduced postoperative complications, early patient release,
      and favorable results. LPP, however, necessitates a high level of surgical
      expertise, especially with regard to reanastomosis. Knotless self-anchoring
      barbed sutures have also been introduced into aesthetic surgery and wound
      closure. We compared a self-retaining suture (SRS) Quill((r)) (Angiotech, Canada)
      with a standard monofilament suture to further investigate their biomechanical
      and urodynamic aspects. MATERIALS AND METHODS: We analyzed breaking strength and
      stiffness between SRS 4.0, 3.0, and polydioxanone suture (PDS((r))) 4.0 (Ethicon,
      Germany) using a biomechanical testing unit. Urodynamic evaluations were
      performed in the porcine upper urinary tract, closing a longitudinal incision
      either with SRS 4.0 (without knots) or with PDS 4.0 (five knots each end). Suture
      line shortening, suture time, tightness, and intrapelvic pressure were measured.
      RESULTS: SRS 4.0 breaks at a mean of 11.57 N (standard deviation [SD]=1.25,
      stiffness 172.8 N/mm(2), SD=10.84), SRS 3.0 at 16.01 N (1.81), and PDS 4.0 at
      18.41 N (0.75, 128.9 N/mm(2), 7.45). SRS 4.0 results in a suture line shortening
      from mean 3.08 to 2.26 mm (-26.6%) while PDS 4.0 shortens from 3.05 to 1.81 mm (
      40.7%). The maximum intrapelvic pressure demonstrated no difference, and leakage
      was seen in 50% of the cases. Suture time was significantly decreased with SRS
      use (SRS 4.0 277 s and PDS 4.0 364 s). CONCLUSION: SRS offers immediate tissue
      adaption with reduced suture line shortening and equal tightness compared with
      nonbarbed material in vitro. Knotless suturing using SRS is time efficient and
      appears to be an excellent material for LPP.

PMID- 21905846
TI  - Effects of subinhibitory concentrations of ciprofloxacin on Staphylococcus
      saprophyticus adherence and virulence in urinary tract infections.
AB  - BACKGROUND AND PURPOSE: Staphylococcus saprophyticus is a frequent cause of both
      uncomplicated and complicated urinary tract infections (UTI) in young females and
      has recently been established as the most prominent gram-positive uropathogen.
      Although the effects of subinhibitory concentrations of antimicrobials on
      numerous other pathogenic bacteria have been studied, little is known regarding
      how S saprophyticus responds under such conditions. MATERIALS AND METHODS: In
      this study, we investigated the effects of subminimum inhibitory concentrations
      (MIC) of ciprofloxacin (CIP) on S saprophyticus attachment to glass microscope
      slides, ureteral stent material, and T24 bladder cells, as well as its effects on
      S saprophyticus-induced proinflammatory cytokine expression in bladder cells.
      RESULTS: Adherence to glass microscope slides, ureteral stent material, and
      bladder cell monolayers were all significantly increased in the presence of sub
      MIC levels of CIP. While the S saprophyticus challenge of T24 bladder cell
      monolayers significantly upregulated both interleukin (IL)-6 and IL-8 expression,
      sub-MIC CIP abrogated these effects, returning their secretion to control levels.
      CONCLUSIONS: Our results demonstrate that exposure to sub-MIC CIP increases S
      saprophyticus adherence to both abiotic and biotic surfaces including urinary
      device material and cultured bladder cells. In addition, low levels of this
      antimicrobial downregulate S saprophyticus-stimulated proinflammatory cytokine
      secretion in the bladder. These changes may make S saprophyticus more effective
      at colonizing the urinary tract and highlights the need for clinicians to
      consider the impact of subinhibitory concentrations of antimicrobials on bacteria
      when designing treatment strategies to manage UTI.

PMID- 21905847
TI  - Factors determining fluoroscopy time during ureteroscopy.
AB  - PURPOSE: The aim of this study was to prospectively identify predictors of
      radiation exposure during ureteroscopy. PATIENTS AND METHODS: Eighty-five
      consecutive patients who presented for ureteroscopies and laser lithotripsy were
      considered. Fluoroscopy time (FT) was obtained from radiology reports for each
      patient, and clinical data were obtained from chart review. Nine patients were
      excluded (three unconfirmed FTs, four staghorn calculi, one ectopic kidney, and
      one multiple ureteral strictures). Seventy-six patients were included in the
      study. Univariate and multivariate linear regression were used to identify
      factors that determined FT. RESULTS: The patient cohort was 65.8% male with a
      mean age of 52.7 years. Mean FT was 183 s, and mean surgical time was 68.4+/-29
      minutes. Mean stone size was 10+/-5 mm in the greatest dimension. A large
      proportion of patients (50%) had renal stones, multiple stones were present in
      31.6% of cases, and 22.3% of stones were radiolucent. Cases were equally
      distributed between surgeons A and B, and 46% of patients had preoperative
      stents. On multivariate analysis, increased FT was independently associated with
      surgeon A (104 additional seconds per case, P<0.001), longer duration of surgery
      (14 s per 10 minutes, P<0.001), and male patients (54 s per procedure, P=0.02).
      Age, stone characteristics, presence of ureteral stent, and stone-free status did
      not correlate with FT. CONCLUSIONS: Surgeon behavior, longer duration of surgery,
      and male gender were significant predictors of FT and, hence, radiation exposure
      during ureteroscopy. In the present study, stone characteristics were not found
      to be predictors of FT.

PMID- 21905848
TI  - Needle renal displacement technique for the percutaneous approach to the superior
      calix.
AB  - We describe a new renal displacement technique using an 18-gauge needle to
      facilitate superior calix puncture and consequently to decrease intrathoracic
      morbidity. Initially, a lower or middle calix is punctured with an 18-gauge
      needle. Then, the proximal end of the needle is progressively pushed in the
      cephalic direction. Therefore, the kidney is pushed caudally by the lever
      maneuver. This technique has also been used to immobilize the kidney or to
      reorient complex and malrotated kidneys.

PMID- 21905849
TI  - Factors affecting operative time during percutaneous nephrolithotomy: our
      experience with the complete supine position.
AB  - BACKGROUND AND PURPOSE: Operative time influences surgical outcomes, operation
      related and indirectly anesthesia-related complications. We investigated
      variables that affect operative time during percutaneous nephrolithotomy (PCNL)
      with the complete supine position. PATIENTS AND METHODS: We reviewed data of 120
      patients who underwent complete supine PCNL by one surgeon. Correlation between
      age, sex, body mass index (BMI), preoperative serum creatinine and hemoglobin
      levels, history (stone surgery, shockwave lithotripsy (SWL), hypertension,
      diabetes), stone (side, opacity, burden, complexity), imaging for access, calix
      for access, number of tracts, and tubeless approach with operative time were
      assessed by univariate and multivariate statistical tests. RESULTS: Mean
      operative time was 60.62+/-30.70 minutes. In univariate analysis, age, sex,
      groups of BMI, hypertension, diabetes, previous stone surgery and SWL, stone
      opacity, operation side, number of tracts, and tubeless approach had no effect on
      operative time. BMI (P=0.029, negative correlation), stone burden (P=0.001,
      positive correlation), imaging for access (P=0.001, fluoroscopy<ultrasonography),
      calix for access (P=0.035, upper>lower>middle) and probably complex stones
      (P=0.057, complex>noncomplex) were effective factors on operative time. Multiple
      linear regression revealed association between BMI (P=0.000, negative
      correlation), stone burden (P=0.005, positive correlation), imaging for access
      (P=0.000, fluoroscopy<ultrasonography), and calix for access (P=0.023) with
      operative time. In lower calix access, mean operative time was less than upper
      calix access (P=0.022, significant) and higher than middle calix access (P=0.930,
      nonsignificant). CONCLUSIONS: BMI, stone burden, imaging for access, and calix
      for access were effective parameters on operative time in complete supine PCNL.
      Groups of BMI, previous stone surgery and SWL, number of tracts, and tubeless
      approach had no effect on operative time.

PMID- 21905851
TI  - Evaluation of zotarolimus-eluting metal stent in animal ureters.
AB  - BACKGROUND AND PURPOSE: Drug-eluting stents proved to minimize neointimal
      hyperplasia in coronary vessels. Hyperplastic reaction is the most common
      unwelcome event related to the use of metal mesh stents in the ureter. We
      evaluated the effect of zotarolimus-eluting stent (ZES) Endeavor Resolute in the
      porcine and rabbit ureter. MATERIALS AND METHODS: A ZES and a bare metal stent
      (BMS) were inserted in each ureter of 10 pigs and 6 rabbits. The insertion was
      performed by the retrograde approach. CT was used for the evaluation of porcine
      ureters while intraoperative intravenous urography (IVU) was used for rabbit
      ureters. The follow-up included CT or IVU every week for the following 4 weeks
      for pigs and 8 weeks for rabbits. Renal scintigraphies were performed before
      stent insertion and during the third week in all animals. Optical coherence
      tomography (OCT) has been used for the evaluation of the luminal and intraluminal
      condition of the ureters with stents. Histopathologic examination of the these
      ureters embedded in glycol-methacrylate was performed. RESULTS: Hyperplastic
      reaction was present in both stent types. BMSs in seven porcine ureters were
      completely obstructed while porcine ureters with ZES stents had hyperplastic
      tissue that did not result in obstruction. Two rabbit ureters with BMS stents
      were occluded while no ZES was associated with ureteral obstruction. The function
      of the seven porcine renal units and the two rabbit units with obstructed ureters
      with stents was compromised. The OCT revealed increased hyperplastic reaction in
      the ureters with BMS stents in comparison with those with ZESs. Although,
      hyperplastic reaction was present in all cases, pathologic examination revealed
      significantly more hyperplastic reaction in BMSs. CONCLUSION: ZESs in the pig and
      rabbit ureter were not related to hyperplastic reaction resulting in stent
      occlusion. These stents were related to significantly lower hyperplastic reaction
      in comparison with BMSs while inflammation rates were similar for both stent
      types.

PMID- 21905850
TI  - The comparison of three renal tumor scoring systems: C-Index, P.A.D.U.A., and
      R.E.N.A.L. nephrometry scores.
AB  - BACKGROUND AND PURPOSE: The centrality-index (C-Index), preoperative aspects and
      dimensions used for anatomic (P.A.D.U.A.) classification, and
      radius.exophyic/endophytic.nearness.anterior/posterior.location (R.E.N.A.L.)
      nephrometry schemes were developed as standardized scoring systems (SS) to
      quantify anatomic characteristics of kidney tumors. The objective of this study
      was to establish reliability and assess relationships between these three SS and
      perioperative and postoperative variables. PATIENTS AND METHODS: A retrospective
      chart review was performed in 101 patients who underwent laparoscopic partial
      nephrectomy. The nephrometry schemes were correlated with intraoperative and
      postoperative parameters using Spearman correlations. In addition, interobserver
      reliability was assessed on 50 of the patients by interclass correlations
      comparing the scores assigned by two residents and one fellow who reviewed
      preoperative CT studies of these patients. RESULTS: The interobserver correlation
      was 0.84 for the C-Index, 0.81 for the P.A.D.U.A., and 0.92 for the R.E.N.A.L.
      scoring systems, demonstrating excellent interobserver reliability. All three SS
      were significantly associated with warm ischemia time (WIT) (C-Index, P=-0.44;
      P.A.D.U.A., P=0.25; R.E.N.A.L., P=0.32) and percent change in creatinine level (C
      Index, P=- 0.33; P.A.D.U.A., P=0.37; R.E.N.A.L., P=0.37). There were no
      significant associations between any of the three SS assessed and the occurrence
      of complications, operative time, or estimated blood loss. No significant
      correlation was found between the P.A.D.U.A. and R.E.N.A.L. SS and length of
      stay; however, C-Index did show a significant relationship for patients with
      lower scores having longer hospital stays (P=-0.21). CONCLUSIONS: All three
      scoring systems demonstrated reliability among observers and represent novel
      methods of quantitatively describing renal tumors. They were all associated with
      WIT, percent change in creatinine level, and tumor size. They did not, however,
      correlate with any other perioperative parameters investigated. At this time,
      these SS provide a common language for describing renal tumors.

PMID- 21905852
TI  - Treatment of persistent idiopathic facial pain (PIFP) with a low-level energy
      diode laser.
AB  - OBJECTIVE: The purpose of this study was to test the therapeutic efficacy of low-
      level energy diode laser on persistent idiopathic facial pain (PIFP). BACKGROUND
      DATA: PIFP has presented a diagnosis and management challenge to clinicians. Many
      patients were misdiagnosed, which resulted in unnecessary dental procedures. Low
      level energy diode laser therapy has been applied to different chronic and acute
      pain disorders, including neck, back, and myofacial pain; degenerative
      osteoarthritis; and headache, and it may be an effective alternative treatment
      for PIFP. METHODS: A total of 16 patients, who were diagnosed with PIFP, were
      treated with an 800-nm wavelength diode laser. A straight handpiece having an end
      size of 0.8 cm in diameter, or an angled handpiece with an end size of 0.5 cm in
      diameter was used. When laser was applied, the handpiece directly contacted the
      involved symptomatic region with an energy density of 105 J/cm(2). Overall pain
      and discomfort was analyzed with a 10-cm visual analogue scale (VAS) before and
      after treatment. RESULTS: All patients received diode laser therapy between 1 and
      10 times. The average pain score was 7.4 before the treatment (ranging from 2.9
      to 9.8), and 4.1 after the treatment. An average pain reduction of 43.87%
      (ranging from 9.3% to 91.8%) was achieved. The pain remained unchanged at a lower
      level for up to 12 months. CONCLUSIONS: Low-level energy diode laser may be an
      effective treatment for PIFP.

PMID- 21905874
TI  - Detection and characterization of aparmycin-resistant Escherichia coli from
      humans in Korea.
AB  - To investigate apramycin resistance in humans in Korea, a total of 138 human
      Escherichia coli strains confirmed as gentamicin-resistant were collected from
      Korean Culture Collection Antimicrobial-Resistant Microbes. Apramycin resistance
      (minimum inhibitory concentrations >=1,024 MUg/ml) was observed in 16 (11.6%) of
      the 138 gentamicin-resistant E. coli (GREC) strains. Among the seven different
      kinds of aminoglycoside resistance genes tested, only four kinds were detected in
      the apramycin-resistant GREC strains: aac (3)-II, aac (3)-III, aac (3)-IV, and
      armA. The aac (3)-IV gene was found in all apramycin-resistant GREC strains,
      whereas aac(3)-II, aac(3)-III, and armA genes were detected in 8 (50.0%), 6
      (37.5%), and 1 (6.3%) GREC strains resistant to apramycin, respectively. Of 16
      apramycin-resistant GREC strains, transfer of apramycin resistance was observed
      in seven (43.8%), and co-transfer of resistance to other antimicrobials along
      with apramycin resistance was also found in four strains (25.0%) by broth mating.
      The results of this study suggest that more prudential use of apramycin in
      animals is needed.

PMID- 21905875
TI  - Improved cellular immune response elicited by a ubiquitin-fused DNA vaccine
      against Mycobacterium tuberculosis.
AB  - This study evaluated the immune response elicited by a ubiquitin (Ub)-fused MPT64
      DNA vaccine against Mycobacterium tuberculosis. BALB/c mice were vaccinated with
      plasmid DNA encoding MPT64 protein, Ub-fused MPT64 DNA vaccine (UbGR-MPT64), and
      negative DNA vaccines, respectively. MPT64 DNA vaccine immunization induced a Thl
      polarized immune response. The production of Thl-type cytokine (interferon-gamma
      [IFN-gamma]) and proliferative T cell responses were enhanced significantly in
      mice immunized with UbGR-MPT64 fusion DNA vaccine, compared with nonfusion DNA
      vaccine. Moreover, this fusion DNA vaccine also resulted in an increased relative
      ratio of IgG2a to IgGl and the cytotoxicity of T cells. IFN-gamma intracellular
      staining of splenocytes indicated that UbGR-mpt64 fusion DNA vaccine activated
      CD4+ and CD8+ T cells, particularly CD8+ T cells. Thus, this study demonstrated
      that the UbGR-MPT64 fusion DNA vaccine inoculation could improve antigen-specific
      cellular immune responses, which is helpful for protection against TB.

PMID- 21905876
TI  - Towards a better understanding and management of pain: a public health mandate.

PMID- 21905877
TI  - Characteristics of Iranian women seeking drug treatment.
AB  - BACKGROUND: In the west, men are twice as likely as women to develop a drug
      problem, but female users have higher rates of morbidity than male users. Iran
      has the world highest per capita opiate consumption, but little is known about
      female drug users. In 2007, we established a free methadone clinic with ancillary
      services for female drug users in South Tehran. The aim was to explore the
      characteristics of female drug users seeking treatment for heroin dependence in
      Iran. Clients were interviewed about demographic characteristics, drug use and
      treatment history, and drug-related health problems. Urine and blood samples were
      collected and tested for morphine, HIV, hepatitis C virus (HCV), and sexually
      transmitted infections (STIs). METHODS: Between August 2007 and October 2008, 78
      women completed a baseline interview. The median age was 37 years, the main
      ethnic background was Persian (65%), and half of the clients were married. Opium
      and heroin and opium use was reported by 69% (n=54) and 87% (n=68) of clients,
      respectively. The mean duration of heroin use problems was 10.5 years, and only
      20% of women reported ever having received drug treatment. HIV and HCV
      seroprevalence was 5% and 24%, respectively. Forty percent were sexually active
      when interviewed, and one third tested positive for an STI. Women had poor social
      functioning, high levels of depression, and poor general health. RESULTS AND
      CONCLUSIONS: Our clients were dependent users with a multitude of problems who
      had little or no contact with treatment agencies before this study. Many clients
      had made a transition from using opium to using heroin, and some had commenced
      injecting, placing them at risk for HIV and HCV infection. More women-only drug
      treatment services are needed to facilitate women's entry into drug treatment.

PMID- 21905878
TI  - Biosurveillance where it happens: state and local capabilities and needs.
AB  - In recent years, improved biosurveillance has become a bipartisan national
      security priority. As has been pointed out by the National Biosurveillance
      Advisory Subcommittee and others, building a national biosurveillance enterprise
      requires having strong biosurveillance systems at the state and local levels, and
      additional policies are needed to strengthen their biosurveillance capabilities.
      Because of the foundational role that state and local health departments play in
      biosurveillance, we sought to determine to what extent state and local health
      departments have the right capabilities in place to provide the information
      needed to detect and manage an epidemic or public health emergency-both for state
      and local outbreak management and for reporting to federal agencies during
      national public health crises. We also sought to identify those policies or
      actions that would improve state and local biosurveillance and make
      recommendations to federal policymakers who are interested in improving national
      biosurveillance capabilities.

PMID- 21905879
TI  - Collagen-induced arthritis as an animal model for rheumatoid arthritis: focus on
      interferon-gamma.
AB  - Rheumatoid arthritis (RA), an autoimmune disease causing inflammation,
      destruction, and deformity of the joints, affects around 1% of the world
      population. It is a systemic disease as patients exhibit extra-articular
      manifestations as well. Collagen-induced arthritis (CIA) in DBA/1 mice is one of
      the many animal models used to study possible pathogenic mechanisms of RA. It
      involves immunizing mice with collagen type II in complete Freund's adjuvant.
      Here we briefly review the general characteristics of RA and CIA and present an
      overview of data obtained by studying CIA in several gene knockout mice. In
      particular, detailed analysis of CIA in interferon-gamma (IFN-gamma) receptor
      deficient mice has pin-pointed IFN-gamma as an important cytokine in the
      pathogenesis and has exposed new functions of IFN-gamma in immunological
      processes. Pilot trials with exogenous IFN-gamma in RA have been indicative of a
      beneficial effect. That improvement of the disease symptoms by IFN-gamma
      treatment was not spectacular may be explained by the fact that RA is a
      heterogeneous disease in which the severity of the autoimmune disease is strongly
      determined by environmental factors.

PMID- 21905880
TI  - Global gene expression profile of osteoblast-like cells grown on polyester
      copolymer scaffolds.
AB  - One of the principal goals in tissue engineering is to produce scaffold materials
      that will guide cells to differentiate and regenerate functional replacement
      tissue at the site of injury. Poly(l-lactide-co-1,5-dioxepan-2-one) [Poly(LLA-co
      DXO)], a potential scaffolding material for bone tissue engineering, has high
      hydrophilicity. Previous in vitro studies using human osteoblast-like cells
      (HOBs) demonstrated greater cytocompatibility and enhanced osteogenic
      differentiation when HOBs were seeded onto Poly(LLA-co-DXO) compared to Poly(l
      lactide) [P(LLA)] scaffolds. The aim of the study was to identify the gene
      expression profiles of HOBs obtained from alveolar bone and grown on Poly(LLA-co
      DXO) biodegradable polymer scaffolds compared to P(LLA) one. Illumina HumanWG-6
      v3.0 Expression BeadChips were used for the gene expression analysis. Several
      genes were found as differentially expressed at 24 h and at 21 days. Expression
      of genes related to cell adhesion, cytoskeleton, antiapoptosis, proliferation,
      and bone mineralization was influenced by adding the monomer 1,5-dioxepan-2-one
      to the L-lactide. Genes related to three biological pathways involving Integrin,
      Notch, and Ras were found to be upregulated. For selected genes, results were
      confirmed by quantitative reverse transcriptase-polymerase chain reaction.
      Further, calcium content analysis revealed a significant enhancement of calcium
      deposition on both tested scaffolds. This observation was confirmed by Von Kossa
      and Alizarin Red S staining. Findings of this study are relevant to a better
      understanding of the molecular mechanisms underlying the behavior of HOBs in bone
      regenerative procedure.

PMID- 21905882
TI  - Effect of different storage media on the regenerative potential of autogenous
      bone grafts: a histomorphometrical analysis in rabbits.
AB  - The success of autogenous bone graft is related to the graft cell viability. In
      bone-grafting procedures, harvested grafts are often maintained in extraoral
      media while the recipient site is prepared. The aim of this study was to evaluate
      in vivo the effect of storage media over autogenous bone grafts during the
      transsurgical time. Two grafts were removed bilaterally from the calvaria of 18
      rabbits. One graft was immediately fixed in the mandibular angle (control group),
      and the other was maintained in air exposure (dry group), 0.9% NaCl solution
      (saline group), or platelet-poor plasma (PPP group) during 30 minutes and
      stabilized in the symmetrical location of control grafts. After 28 days, the
      animals were euthanized and the bone fragments were removed, demineralized, and
      embedded in paraffin. Histological evaluation was performed under light
      microscope. Empty lacunae and bone graft area quantification were carried out for
      the sections. The histomorphometrical analysis revealed reduction of the graft
      area and increase of empty lacunae in the dry group when compared with control.
      No significant differences were found in the number of empty lacunae or bone
      graft area between the saline group and its control and also between the PPP
      group and its control. The dry group showed more empty lacunae and less graft
      area than the saline and PPP groups. In accordance with the results, PPP and
      physiologic solution demonstrated osteocyte preservation and bone graft area
      maintenance, being satisfactory storage media for autogenous bone grafts during
      the transsurgical period. 

PMID- 21905881
TI  - In vitro cartilage tissue engineering using adipose-derived extracellular matrix
      scaffolds seeded with adipose-derived stem cells.
AB  - Extracellular matrix (ECM) secreted from the resident cell of tissue is an ideal
      biomaterial evolved by nature. Cartilage is also built from well-organized ECM
      components in a gel-like structure with a high collagen and proteoglycan content.
      Here, we explored cartilage tissue engineering using ECM scaffolds seeded with
      stem cells. Both scaffolds and stem cells were isolated from human adipose
      tissue, which is abundant and easily harvested in the human body. The human ECM
      scaffolds contained various endogenous bioactive factors, including transforming
      growth factor-beta1 (TGF-beta1, 8782+/-4989 pg/g, dry ECM), insulin growth factor
      1 (13319+/-1388 pg/g, dry ECM), basic fibroblast growth factor (82373+/-9572
      pg/g, dry ECM), and vascular endothelial growth factor (25647+/-2749 pg/g, dry
      ECM). A composite of ECM and stem cells was prepared and cultured in chondrogenic
      medium (with 10 ng/mL TGF-beta1 or not) for 45 days. The volumes and weights of
      the composites increased during culture and the surface gradually became smooth.
      Cell viability remained high throughout the 45 days of in vitro culture.
      Composites showed the formation of cartilage-like tissue with the synthesis of
      cartilage-specific proteins such as collagen and glycosaminoglycan. Important
      chondrogenic markers were expressed including Sox-9, aggrecan, and collagen type
      II and XI. These results demonstrate that a cell/ECM composite containing
      endogenous bioactive factors could provide biochemical cues for the promotion of
      cartilage formation.

PMID- 21905883
TI  - Ridge expansion and immediate placement with piezosurgery and screw expanders in
      atrophic maxillary sites: two case reports.
AB  - Endosseous dental implants may require bone augmentation before implant
      placement. Herein is described an approach to edentulous ridge expansion with the
      use of piezosurgery and immediate placement of implants. This may allow for a
      shortened treatment time and the elimination of donor-site morbidity. Two cases
      are reported. This technique uses a piezoelectric device to cut the crestal and
      proximal facial cortices. Space is then created with motorized osteotomes to
      widen the split ridge. This technique allows for expansion of narrow,
      anatomically limiting, atrophic ridges, creating space for immediate implant
      placement. The facial and lingual cortices provide support with vital osteocytes
      for osteogenesis. The 2 patients presented had adequate bone height for implant
      placement but narrow edentulous ridges. In patient 1 at site #11, the ridge crest
      was 3.12 mm thick and was expanded to accept a 4.3 mm * 13 mm implant. The
      resulting ridge width was 8.88 mm, which was verified using cone beam
      computerized tomography (CBCT). In patient 2 at site #8 and site #9, the narrow
      ridge was expanded using the same technique to accept 2 adjacent 3.5 mm * 14 mm
      implants. The implants were restored to a functional and esthetic outcome.

PMID- 21905884
TI  - Socket preservation and sinus augmentation using a medical grade calcium sulfate
      hemihydrate and mineralized irradiated cancellous bone allograft composite.
AB  - Regeneration and preservation of bone after the extraction of a tooth are
      necessary for the placement of a dental implant. The goal is to regenerate
      alveolar bone with minimal postoperative pain. Medical grade calcium sulfate
      hemihydrate (MGCSH) can be used alone or in combination with other bone grafts;
      it improves graft handling characteristics and particle containment of particle
      based bone grafts. In this case series, a 1:1 ratio mix of MGCSH and mineralized
      irradiated cancellous bone allograft (MICBA) was mixed with saline and grafted
      into an extraction socket in an effort to maintain alveolar height and width for
      future implant placement. MGCSH can be used in combination with other bone grafts
      and can improve handling characteristics and graft particle containment of
      particle-based bone grafts. In the cases described, we found that an MGCSH:MICBA
      graft can potentially be an effective bone graft composite. It has the ability to
      act as a space maintainer and as an osteoconductive trellis for bone cells,
      thereby promoting bone regeneration in the extraction socket. MGCSH, a cost
      effective option, successfully improved MICBA handling characteristics, prevented
      soft tissue ingrowth, and assisted in the regeneration of bone. 

PMID- 21905886
TI  - Influence of fine threads and platform-switching on crestal bone stress around
      implant-a three-dimensional finite element analysis.
AB  - The aims of this study were to investigate the effect of implant fine threads on
      crestal bone stress compared to a standard smooth implant collar and to analyze
      how different abutment diameters influenced the crestal bone stress level. Three
      dimensional finite element imaging was used to create a cross-sectional model in
      SolidWorks 2007 software of an implant (5-mm platform and 10 mm in length) placed
      in the premolar region of the mandible. The implant model was created to resemble
      a commercially available fine thread implant. Abutments of different diameters
      (5.0 mm: standard, 4.5 mm, 4.0 mm, and 3.5 mm) were loaded with a force of 100 N
      at 90 degrees  vertical and 40 degrees  oblique angles. Finite element analysis
      was done in COSMOSWorks software, which was used to analyze the stress patterns
      in bone, especially in the crestal region. Upon loading, the fine thread implant
      model had greater stress at the crestal bone adjacent to the implant than the
      smooth neck implant in both vertical and oblique loading. When the abutment
      diameter decreased progressively from 5.0 mm to 4.5 mm to 4 mm and to 3.5 mm the
      thread model showed a reduction of stress at the crestal bone level from 23.2 MPa
      to 15.02 MPa for fine thread and from 22.7 to 13.5 MPa for smooth collar implant
      group after vertical loading and from 43.7 MPa to 33.1 MPa in fine thread model
      and from 36.9 to 20.5 MPa in smooth collar implant model after oblique loading.
      Fine threads increase crestal stress upon loading. Reduced abutment diameter that
      is platform switching resulted in less stress translated to the crestal bone in
      the fine thread and smooth neck. 

PMID- 21905885
TI  - Immediate loading of single post-extractive implants in the anterior maxilla: 12
      month results from a multicenter clinical study.
AB  - The purpose of the study was to evaluate survival and peri-implant bone levels of
      single, immediately loaded post-extractive implants in the anterior maxilla 12
      months after implant placement. Thirty-six consecutive patients from 3 study
      centers were included in the study. The concerned sites were upper premolars,
      canines, and incisors. For each patient the following data were recorded: reason
      for tooth extraction, bone quality, implant size, and final insertion torque.
      Implants were placed using a flapless technique and immediately loaded with a
      nonoccluding temporary restoration. Final restorations were provided 4 months
      later. Peri-implant bone resorption was evaluated radiographically after 6 and 12
      months. The average final insertion torque was 70.55 Ncm. One implant inserted in
      D3 quality bone with a 35-Ncm seating torque was lost. All other implants had a
      final insertion torque ranging between 50 and 80 Ncm. The average peri-implant
      bone loss was 0.437 and 0.507 mm at 6 and 12 months, respectively. All the sites
      maintained excellent papillae and peri-implant soft-tissue conditions. The
      resulting 1-year success rate was 97.2%. Immediate nonfunctional loading of
      single post-extractive implants in the anterior maxilla is a predictable
      treatment. And it seems that achieving high insertion torques by placing self
      tapping/self-condensing implants in an underprepared osteotomy is favorable.

PMID- 21905887
TI  - Craniofacial implant-retained auricular prosthesis: a case report.
AB  - Implants provide patients with a safe and reliable method for anchoring auricular
      prostheses that enable restoration of their normal appearance and offer improved
      quality of life. In this case report, an auricular prosthesis was fabricated for
      a patient who had lost his right external ear in a traffic accident. Extraoral
      implants and bar-and-clip retention for the proper connection of the auricular
      prosthesis to the implant were used. 

PMID- 21905888
TI  - Development of a rat model of bisphosphonate-related osteonecrosis of the jaw
      (BRONJ).
AB  - The purpose of this study was to develop a rat model predictive of bisphosphonate
      related osteonecrosis of the jaw (BRONJ) after exodontias. Thirty female rats
      were randomized into 2 groups, control and experimental. The experimental group
      received 2 intravenous injections of zoledronate (20 MUg/kg). The mesial root of
      the right mandibular first molar was extracted. Rats were euthanized at 0, 4, and
      8 weeks. Bone mineral density (BMD), collagen breakdown (pyridinium [PYD]),
      vascular regeneration (VEGF), and histology were examined. A trend toward higher
      PYD values was suggested in control vs experimental groups after wounding. Serum
      VEGF increased significantly after wounding for both control and experimental
      groups. After 8 weeks, VEGF continued to rise for the experimental group only. In
      the extraction socket area, BMD was significantly lower after wounding in control
      vs. zoledronate-treated rats. Histology sections from experimental groups showed
      bacteria and bone necrosis. Consistent findings of BRONJ features similar to
      those in humans were observed after zoledronate treatment.

PMID- 21905889
TI  - An early loaded implant-supported mandibular complete arch fixed prosthesis in a
      young completely edentulous patient: a case report.
AB  - The restoration of the mandibular arch up to the first molars with 5 one-piece
      implants presents a viable and cost-effective treatment plan in patients with
      adequate bone volume and favorable ridge relationships. The early loading of the
      implants with a provisional restoration reduces the period of edentulousness and
      restores the patient's ability to eat, talk, and smile effectively. Implants in
      younger patients prevent resorption of the residual alveolar ridge. This article
      presents a case report of the restoration of an edentulous mandibular arch with
      an early loaded implant-supported fixed restoration in a young patient. 

PMID- 21905890
TI  - Evaluation of soft tissues around single tooth implants in the anterior maxilla
      restored with cemented and screw-retained crowns.
AB  - Implant-supported restorations can be attached as screw-retained or cemented
      prostheses. In both situations, the characteristics of the soft tissues around
      the implants are crucial for oral rehabilitation and patient satisfaction.
      Therefore, this study uses the Pink Esthetic Score (PES), which allows evaluation
      of gingival esthetics around implants, to evaluate the soft tissues around
      implants in the anterior maxilla rehabilitated with cemented prostheses (CP) and
      screw-retained prostheses (SP). Forty implants placed in the anterior maxilla
      were evaluated, and these had been rehabilitated with prosthetic crowns for a
      minimum of 1 year. Periodontal examination was performed to evaluate probing
      depth (PD) and bleeding on probing (BOP) of the implant and the corresponding
      natural tooth. The total mean (+/-SD) PES for SP was 10.73 (+/-1.98) and 10.41
      (+/-2.67) for CP, which was not statistically significant (P >= .05). Periodontal
      examination revealed that CP and SP showed no difference for BOP (P >= .05).
      Differences were only detected in PD when comparing the reference teeth of both
      groups to CP and SP (P <= .05). The present study demonstrates that the PES
      proved to be an efficient index to assess peri-implant tissues, and that the type
      of crown retention does not influence the health and quality of the soft tissues
      around implants.

PMID- 21905891
TI  - Ultrasonic oscillations for conservative retrieval of a rare fracture of implant
      healing abutment.
AB  - Dental implants can be rendered useless because of complications related to
      implant components such as the fracture of abutment screw and prosthetic
      retaining screw. Removal of such fractured fragments is therefore deemed
      necessary for the sake of prosthetic restoration. This case report presents a
      rare incident of healing abutment fracture and details the stepwise and probably
      the most conservative clinical technique using ultrasonic oscillations for
      retrieval of fractured screw fragment without affecting the internal surface of
      the implant. The management was based on the fact that the screw, being an
      inclined plane, will unthread when subjected to continuous vibrations. 

PMID- 21905892
TI  - PEEK dental implants: a review of the literature.
AB  - The insertion of dental implants containing titanium can be associated with
      various complications (eg, hypersensitivity to titanium). The aim of this article
      is to evaluate whether there are existing studies reporting on PEEK
      (polyetheretherketone) as an alternative material for dental implants. A
      systematic literature search of PubMed until December 2010 yielded 3 articles
      reporting on dental implants made from PEEK. One article analyzed stress
      distribution in carbon fiber-reinforced PEEK (CFR-PEEK) dental implants by the 3
      dimensional finite element method, demonstrating higher stress peaks due to a
      reduced stiffness compared to titanium. Two articles reported on investigations
      in mongrel dogs. The first article compared CFR-PEEK to titanium-coated CFR-PEEK
      implants, which were inserted into the femurs and evaluated after 4 and 8 weeks.
      The titanium-coated implants showed significantly higher bone-implant contact
      (BIC) rates. In a second study, implants of pure PEEK were inserted into the
      mandibles beside implants made from titanium and zirconia and evaluated after 4
      months, where PEEK presented the lowest BIC. The existing articles reporting on
      PEEK dental implants indicate that PEEK could represent a viable alternative
      material for dental implants. However, further experimental studies on the
      chemical modulation of PEEK seem to be necessary, mainly to increase the BIC
      ratio and to minimize the stress distribution to the peri-implant bone. 

PMID- 21905893
TI  - Clinical, histological, and histomorphometrical analysis of maxillary sinus
      augmentation using inorganic bovine in humans: preliminary results.
AB  - The aim of the present study was to evaluate bone formation after maxillary sinus
      augmentation using bovine bone substitute material Bio-Oss alone by means of
      clinical, histological, and histomorphometrical examination of human biopsies.
      Deproteinized bovine bone (DPBB, Bio-Oss) was used to fill cavities after
      elevation of the sinus mucosa following major sinus pneumatization. Twenty
      patients with edentulous posterior maxillae were treated with 20 sinus
      augmentation procedures using a 2-stage technique. Residual lateral maxillary
      bone height was less than 3 mm. Forty-nine Straumann endosseous implants were
      used to complete the implant-prosthetic rehabilitation. Forty cylinder-shaped
      bone biopsies were taken from the augmented maxillary region 8 months after
      grafting during the second-stage surgery before implant placement. All implants
      were loaded 3 months after insertion, and no failures were recorded.
      Histomorphometrical analysis showed an average percentage of newly formed bone of
      17.6% (+/- 2.8%) and a proportion of residual bone substitute material of 29.9%
      (+/- 4.9%) of the total biopsy area. Intimate contact between newly formed bone
      and Bio-Oss was detected along 28.2% (+/- 6.8%) of the particle surfaces. The
      results also showed that in all cases, the DPBB granules had been interconnected
      by bridges of vital newly formed bone. Inorganic bovine bone appears to be
      biocompatible and osteoconductive, and it can be used with success as a bone
      substitute in maxillary sinus augmentation procedures.

PMID- 21905894
TI  - Influence of surface nano-roughness on osseointegration of zirconia implants in
      rabbit femur heads using selective infiltration etching technique.
AB  - This study evaluates osseous healing of selective infiltration-etched (SIE)
      zirconia implants compared to as-sintered zirconia and titanium implants. Twenty
      implants of each group were inserted in 40 adult New Zealand white male rabbits.
      After 4 and 6 weeks, bone blocks containing the implants were retrieved,
      sectioned, and processed to evaluate bone-implant contact (BIC) and peri-implant
      bone density. SIE zirconia implants had significantly higher BIC and marginally
      higher bone density. The results suggest that selective infiltration-etched
      zirconia implant surface may improve implant osseointegration. 

PMID- 21905895
TI  - A technique to salvage a single implant-supported fixed dental prosthesis having
      a nonretrievable implant screw fragment.
AB  - An implant screw fracture is one of the common problems associated with the
      implant components. In some situations, it may not be possible to retrieve the
      fractured implant screws. As a result, clinicians either remove the implant or
      the implant may need to be covered over with soft tissue. The salvage of an
      implant with a nonretrievable screw fragment may be highly beneficial to the
      patients. This report describes a technique to salvage an implant-supported
      single restoration that has a nonretrievable implant screw fragment.

PMID- 21905896
TI  - Retention of implant-supported overdenture with bar/clip and stud attachment
      designs.
AB  - The degree of retention for overdenture attachments depends on design, location,
      and alignment of supporting dental implants and the type of attachments. The aim
      of this study was to evaluate the retention of an implant-supported overdenture
      with different attachment designs. An overdenture was made on an edentulous
      mandibular model with 2 ITI implants (4.1 * 10 mm) in the symphyseal region. Five
      specimens of 8 attachment designs with corresponding abutments and
      superstructures were used: ITI regular Dolder bar with 1 metal clip, ITI regular
      Dolder bar with cantilever and 3 metal clips, Hader bar with 1 plastic clip,
      Hader bar with cantilever and 3 plastic clips, Sphero block abutment with Rhein
      plastic caps (green, white, and pink), and retentive anchor with ITI elliptical
      matrix. The attachments' housings were interchangeable and fixed into the
      overdenture through nut and screw. The overdenture attachments were subjected to
      8 consecutive pulls on a universal testing machine with a crosshead speed of 50.8
      mm/min in the vertical and posteroanterior directions. Analysis of variance and
      Duncan tests were used to determine differences between mean retention values
      (alpha = .05). The highest average value retention was recorded for the ITI
      Dolder bar with cantilever and 3 metal clips in both the vertical and
      posteroanterior directions, respectively (P < .05). The Rhein pink caps had the
      lowest retention in the posteroanterior direction (P < .05). Retention decreased
      over the course of consecutive pulls for all attachments in both directions. The
      type, number, and placement of attachments affect the retention of implant
      supported mandibular overdentures.

PMID- 21905897
TI  - Gingival conditioning in an implant-supported prosthesis: a clinical report.
AB  - The loss of gingival volume is a major challenge for dental surgeons with implant
      supported fixed prosthesis manufactures, particularly from an aesthetics
      perspective in patients with a high smile line. Gingival tissue remodeling can
      help in papillae formation to avoid soft tissue surgery by reestablishing the
      appropriate shape and gingival contour of the tissues. This improves not only the
      aesthetics, but also the phonetics of the patient. This paper describes a
      clinical case of gingival conditioning obtained with interim implant-supported
      fixed partial dentures via incremental addition and adjustment of acrylic resin.
      The purpose of the gingival conditioning was to obtain improved aesthetics.
      Gingival conditioning by gradual pressure application is presented as an easy,
      non-traumatic technique that improves gingival aesthetics. 

PMID- 21905898
TI  - A technique for removal of a fractured implant abutment screw.
AB  - The aim of this technique report was to present a procedure for removal of a
      fractured implant abutment screw. Whatever the cause, when an abutment fracture
      has occurred, the fractured screw segment inside the implant must be removed. The
      methods used by the clinicians may include the use of an endo-explorer self-made
      screwdriver and the use of implant repair kit available for some implant systems.
      The advantage of the presented method is that it may be extended to other implant
      systems that do not have a special repair kit and also that the technique is
      simple and does not require special equipment. 

PMID- 21905899
TI  - WITHDRAWN: Immediate placement and provisionalization of implant-supported,
      single-tooth restorations: a retrospective study.
AB  - Immediate implant placement into extraction sockets has been widely reported in
      the dental literature, but few studies have evaluated the immediate loading of
      such implants. In this retrospective study, we evaluated 235 implants placed into
      fresh extraction sites utilizing a flapless technique, followed by immediate
      provisionalization with non-functional single-tooth restorations, and definitive
      restoration within 2 weeks. Cumulative survival and success rates were 98.8%
      (mean follow-up = 23.1 months). Periodontitis did not adversely influence the
      outcome. Within the limitations of this study, immediate implant placement and
      restoration followed by definitive loading within 2 weeks achieved outcomes
      comparable to those historically reported for delayed implants.

PMID- 21905900
TI  - Buccal bone plate remodeling after immediate implant placement with and without
      synthetic bone grafting and flapless surgery: radiographic study in dogs.
AB  - Recent studies in animals have shown pronounced resorption of the buccal bone
      plate after immediate implantation. The use of flapless surgical procedures prior
      to the installation of immediate implants, as well as the use of synthetic bone
      graft in the gaps represent viable alternatives to minimize buccal bone
      resorption and to favor osseointegration. The aim of this study was to evaluate
      the healing of the buccal bone plate following immediate implantation using the
      flapless approach, and to compare this process with sites in which a synthetic
      bone graft was or was not inserted into the gap between the implant and the
      buccal bone plate. Lower bicuspids from 8 dogs were bilaterally extracted without
      the use of flaps, and 4 implants were installed in the alveoli in each side of
      the mandible and were positioned 2.0 mm from the buccal bone plate (gap). Four
      groups were devised: 2.0-mm subcrestal implants (3.3 * 8 mm) using bone grafts
      (SCTG), 2.0-mm subcrestal implants without bone grafts (SCCG), equicrestal
      implants (3.3 * 10 mm) with bone grafts (ECTG), and equicrestal implants without
      bone grafts (ECCG). One week following the surgical procedures, metallic
      prostheses were installed, and within 12 weeks the dogs were sacrificed. The
      blocks containing the individual implants were turned sideways, and radiographic
      imaging was obtained to analyze the remodeling of the buccal bone plate. In the
      analysis of the resulting distance between the implant shoulder and the bone
      crest, statistically significant differences were found in the SCTG when compared
      to the ECTG (P = .02) and ECCG (P = .03). For mean value comparison of the
      resulting linear distance between the implant surface and the buccal plate, no
      statistically significant difference was found among all groups (P > .05). The
      same result was observed in the parameter for presence or absence of tissue
      formation between the implant surface and buccal plate. Equicrestally placed
      implants, in this methodology, presented little or no loss of the buccal bone.
      The subcrestally positioned implants presented loss of buccal bone, even though
      synthetic bone graft was used. The buccal bone, however, was always coronal to
      the implant shoulder.

PMID- 21905902
TI  - Evaluation of optimal taper of immediately loaded wide-diameter implants: a
      finite element analysis.
AB  - This study aimed to evaluate the effects of different tapering angles of an
      immediately loaded wide-diameter implant on the stress/strain distribution in
      bone and implant after implant insertion in healed or fresh molar extraction
      sockets. A total of 10 finite element (FE) implant-bone models, including 8.1-mm
      diameter implant, superstructure, and mandibular molar segment, were created to
      investigate the biomechanical behavior of different implant taper angles in
      immediate and delayed placement conditions. The degrees of implant taper ranged
      from 2 degrees  to 14 degrees , and the contact conditions between the
      immediately loaded implants and bone were set with frictional coefficients (MU)
      of 0.3 in the healed models and 0.1 in the extracted models. Vertical and lateral
      loading forces of 189.5 N were applied in all models. Regardless of the degree of
      implant tapering, immediate loading of wide-diameter implants placed in molar
      extraction sockets generated higher stress/strain levels than implants placed in
      healed sockets. In all models, the von Mises stresses and strains at the implant
      surfaces, cortical bone, and cancellous bone increased with the increasing taper
      angle of the implant body, except for the buccal cancellous bone in the healed
      models. The maximum von Mises strains were highly concentrated on the buccal
      cortical struts in the extracted models and around the implant neck in the healed
      models. The maximum von Mises stresses on the implant threads were more
      concentrated in the non-tapered coronal part of the 11 degrees  and 14 degrees 
      tapered implants, particularly in the healed models, while the stresses were more
      evenly dissipated along the implant threads in other models. Under immediate
      loading conditions, the present study indicates that minimally tapered implants
      generate the most favorable stress and strain distribution patterns in extracted
      and healed molar sites.

PMID- 21905903
TI  - The bactericidal effects of an acidified sodium chlorite-containing oral
      moisturizing gel: a pilot study.
AB  - The aim of this study was to examine the bactericidal effects and bactericidal
      time of an acidified sodium chlorite compound gel (ASC-Gel) on bacteria isolated
      from the peri-implant sulci of 10 patients who received implants 3-27 years
      previously, and the depth of each peri-implant sulcus was 5 mm or less.
      Porphyromonas gingivalis (ATCC33277) was used as the control bacterium. Five ASC
      Gel preparations were created by adding 3.3%, 5.0%, 7.0%, 9.0%, and 11.0% citric
      acid (CA) (condition a, b, c, d, and e, respectively) into an oral moisturizing
      gel containing sodium chlorite. The concentrations of chlorine dioxide (ClO2)
      generated in ASC-Gel under conditions (a) to (e) were 12.1, 14.1, 17.2, 21.2, and
      39.3 ppm, respectively. We examined the bactericidal effects of the 5 ASC-Gel
      preparations at volumes of 0.5, 1.0, and 2.0 mL, and measured the bactericidal
      time when 2.0 mL of ASC-Gel was used under condition (e). The bactericidal
      effects of ASC-Gel became significantly greater with increased concentrations of
      CA and ClO2 and with increased usage (0.5-2.0 mL) of the gel. All bacteria were
      killed by using 2.0 mL of ASC-Gel under condition (e). ASC-Gel also needed
      between 45 and 90 minutes to kill all microbes under condition (e). Within the
      limits of the present investigation, these results suggest that ASC-Gel is useful
      as a chemical disinfectant against bacteria in the peri-implant sulcus. Further
      studies are also required to protect teeth, the surface of hydroxyapatite-coated
      implants, and the surrounding soft tissues from effects of chemical dissolution
      such as acid erosion due to the low pH of ASC-Gel. 

PMID- 21905904
TI  - Bone regeneration around immediate implants utilizing a dense
      polytetrafluoroethylene membrane without primary closure: a report of 3 cases.
AB  - Case reports document successful use of a high-density polytetrafluorethylene
      membrane to augment horizontal defects associated with immediately placed
      implants. This membrane, which is designed to withstand exposure (not require
      primary closure) to the oral cavity because it is impervious to bacteria, reduces
      the need for advanced flap management to attain primary closure. Thus, the
      surgical aspect is less complex and the mucogingival architecture of the area can
      be maintained. These cases demonstrate successful use of this application and
      provide evidence for controlled clinical trials to further evaluate this
      technique. 

PMID- 21905908
TI  - Left-sided predominance of hypodontia irrespective of cleft sidedness in a French
      population.
AB  - OBJECTIVE: Individuals with oral clefts exhibit considerably more dental
      anomalies than do individuals without clefts. Our aim was to evaluate the
      prevalence of tooth agenesis in a sample composed of 124 children (81 boys and 43
      girls, mean age 12.5 years) with clefts registered with the Cleft Palate Center
      in Strasbourg (France). DESIGN: Cleft types and dental agenesis were assessed by
      clinical and radiographic examination. Cleft types were divided into four groups
      according to the clinical extent of the cleft (cleft lip only [CL, 12.9%], cleft
      lip and alveolus [CLA, 4%], cleft lip and palate [CLP, 49.2%], and cleft palate
      only [CP, 33.9%]). RESULTS: Of the subjects 63% had evidence of hypodontia:
      maxillary lateral incisors (54%) and upper and lower premolars (32%) were the
      most common missing teeth. The number of dental ageneses associated with CP (54%)
      and CLP (79%) was significantly higher than that with CL (33%). All these
      anomalies were found in proportionately higher frequencies as the severity of the
      cleft increased, and we found left side predominance for hypodontia (p < .01)
      irrespective of cleft sidedness. CONCLUSIONS: Both right-sided and left-sided
      clefts were more frequently correlated with left-sided dental agenesis. This left
      sided prevalence suggests that common signaling malfunctions might be involved,
      both in dental development anomalies and cleft genesis.

PMID- 21905907
TI  - Neuropsychological, behavioral, and academic sequelae of cleft: early
      developmental, school age, and adolescent/young adult outcomes.
AB  - This article reviews behavioral, neuropsychological, and academic outcomes of
      individuals with cleft across three age levels: (1) infancy/early development,
      (2) school age, and (3) adolescence/young adulthood. The review points out that
      attachment, neurocognitive functioning, academic performance/learning, and
      adjustment outcomes are the result of a complex interaction between biological
      and environmental factors and vary with developmental level, sex, and
      craniofacial anomaly diagnosis. The degree to which associated genetic or
      neurodevelopmental conditions may explain inconsistent findings is unknown and
      suggests the need for caution in generalizing from group data on cleft.

PMID- 21905910
TI  - A restricted test of single-word intelligibility in 3-year-old children with and
      without cleft palate.
AB  - OBJECTIVE: In a previous study, children with cleft palate with hard palate
      closure at 12 months of age showed more typical phonological development than did
      children with an unrepaired hard palate at 36 months of age. This finding was
      based on narrow transcription of word initial target consonants obtained from a
      simple naming test. To evaluate the relevance of this finding, we investigated
      how well the children's target words were understood by 84 naive listeners.
      DESIGN: A cross-sectional study. PARTICIPANTS: Data obtained from 28 children
      with unilateral cleft lip and palate, 3 years of age, who received hard palate
      closure at either 12 months (hard palate repaired; HPR) or 36 months (hard palate
      unrepaired; HPU) were compared with data obtained from 14 age-matched, typically
      developing control children. METHODS: Video recordings of the children naming
      target words were shown to 84 naive listeners between 15 and 24 years of age who
      typed the word they heard. RESULTS: The findings of this study indicated that
      naive listeners correctly identified a larger percentage of words in the control
      children followed by children in the HPR group. Children in the HPU group were
      more difficult for the naive listeners to understand. The error of
      retraction/backing of alveolar target consonants to velar place of articulation
      occurred frequently and most often in the HPU group and was found to have a
      negative effect on intelligibility.

PMID- 21905911
TI  - Demographics of orofacial clefts in Canada from 2002 to 2008.
AB  - Objective : Orofacial clefts such as cleft lip, cleft palate, and cleft lip and
      palate are the most frequent congenital anomalies of the head and neck. The
      purpose of this study was to determine the current demographics for orofacial
      clefts in Canada. Methods : A request for data from all Canadian provinces
      (excluding Quebec due to incompatibilities with provincial coding systems) for
      the fiscal years 2002-2003 to 2007-2008 was submitted to the Canadian Institute
      for Health Information. Variables evaluated included gender, cleft type,
      gestational age, birth weight, income quintile, and institution health region.
      Results : Over the period studied, the prevalence of orofacial clefts ranged from
      11.0 to 15.3 per 10,000 live births (1 in 654 to 1 in 909 live births). The
      distribution of cleft types for live births with orofacial clefts was 17% for
      cleft lip, 41% for cleft palate, and 42% for cleft lip and palate, of which cleft
      lip and cleft lip and palate were male dominant (62% and 66% male, respectively)
      and cleft palate was female dominant (56% female). Saskatchewan and Manitoba had
      significantly higher cleft birthrates (P < .05) compared with the other
      provinces. Birth weight and gestational age (but not income quintile) were
      significantly (P < .0001) lower for newborns with orofacial clefting compared
      with those with no cleft. Conclusions : Canada has one of the highest orofacial
      cleft birthrates in the world (prevalence of 12.7 per 10,000 live births,
      approximately 1 in 790 live births). This study presents an updated demographic
      of orofacial clefts in Canadian newborns and may be useful in predicting the
      burden of anticipated health care.

PMID- 21905912
TI  - An overview of immediate root analogue zirconia implants.
AB  - Owing to its excellent biomechanical characteristics, biocompatibility, and
      bright tooth-like color, zirconia has the potential to become a substitute for
      titanium as dental implant material and to be successfully used as root-analogue
      implants by reproducing the contours of the extracted tooth. This article
      presents an overview of the technique of using root analogue zirconia dental
      implants as an immediate implantation material. These implants are replicas of
      the extracted tooth and therefore truly anatomically correct and socket friendly.

PMID- 21905913
TI  - Implant-prosthetic rehabilitation of a patient with nonsyndromic oligodontia: a
      clinical report.
AB  - Oligodontia is defined as the absence of 6 or more permanent teeth due to the
      hypodevelopment of tooth germs. This familial abnormality is attributable to
      various mutations or polymorphisms of genes and associated with malformative
      syndromes. This clinical report presents the multidisciplinary dental treatment
      planning for a 27-year-old woman who exhibited oligodontia. After radiographic
      and clinical evaluations, 7 retained primary teeth and 2 mandibular third molars
      were extracted. Three dental implants were placed into the maxillary alveolar
      process. After the osseointegration period, complete-arch fixed prostheses in
      both maxilla and mandible, supported by a combination of implants and teeth, were
      fabricated. Osseointegration of the implants, peri-implant mucosa health, and
      prosthesis function were assessed every 6 months. At the end of the 3-year
      clinical follow-up, the patient was satisfied with the esthetics, function, and
      phonation of her prosthesis. To attain the best esthetic and biological results,
      an interdisciplinary approach could be used to synergistically combine surgery
      and restorative dentistry for the restoration of maximal esthetics and function.

PMID- 21905914
TI  - Replacement of mandibular posterior teeth with implants in a postmandibular
      resection case: a case report.
AB  - This case report describes the prosthetic rehabilitation of a patient who was
      treated for ameloblastoma by segmental resection of the mandible. Because of the
      size of the defect it was decided to use a healing obturator to facilitate bone
      formation in the defect. At the end of 3 months, bone formation had led to
      complete obliteration of the defect with an almost complete fill to the crest of
      the ridge. The next phase of the treatment was prosthetic rehabilitation. The
      patient preferred a fixed replacement of teeth as opposed to a removable option.
      The final treatment plan was an implant-supported fixed prosthesis that was
      progressively loaded.

PMID- 21905915
TI  - Types of implant surgical guides in dentistry: a review.
AB  - Various techniques have been proposed for the fabrication of surgical guide
      templates in implant dentistry. The objective of this paper is to review the
      associated literature and recent advancements in this field, based on design
      concept. An electronic and hand search of the literature revealed 3 categories,
      namely, nonlimiting, partially limiting, and completely limiting design. Most
      clinicians still adopt the partially limiting design due to its cost
      effectiveness and credibility. Moreover, clinicians use cross-sectional imaging
      during the preimplant assessment of surgical sites.

PMID- 21905916
TI  - Psychosocial, feeding, and drooling outcomes in children with Beckwith Wiedemann
      syndrome following tongue reduction surgery.
AB  - OBJECTIVE: Macroglossia is a common feature of Beckwith Wiedemann Syndrome (BWS).
      Tongue reduction surgery (TRS) is advocated to overcome, or reduce, the secondary
      effects of macroglossia. Macroglossia may affect a child's cosmetic appearance,
      feeding, and drooling function. However, no study has systematically reported on
      feeding, drooling, or psychosocial outcomes preoperatively and postoperatively in
      this group. This study aimed to describe the presurgical and postsurgical
      psychosocial, feeding, and drooling outcomes of children with macroglossia
      associated with BWS and to determine the effect of TRS on these areas. DESIGN:
      Clinical cohort study. PARTICIPANTS: Ten consecutively admitted children with BWS
      (age at surgery from 9 months to 4 years, 9 months [4;9]; mean, 2;7) were
      assessed preoperatively, 3 months postoperatively, and at long-term follow-up.
      MAIN OUTCOME MEASURES: A parental report questionnaire, the Brodsky drooling
      scale, and a feeding rating scale. RESULTS: Parents reported that macroglossia
      had a negative impact cosmetically that was ameliorated following surgery.
      Macroglossia caused a range of feeding difficulties presurgically by preventing
      lip seal and bolus manipulation during the oral preparatory phase. Excessive
      drooling was present in all cases presurgically. This resolved partially across
      the group postsurgically, with almost complete recovery at longer-term follow-up
      assessment. CONCLUSIONS: Presurgically, children show a common profile of feeding
      and drooling impairment with negative effects on cosmetic appearance. Our
      preliminary results demonstrate that TRS has a positive impact on these features
      with good outcomes for children with BWS.

PMID- 21905917
TI  - Isolated congenital hypoplasia of nasal lower lateral cartilages and its
      correction with helical rim and conchal cartilage composite grafts.
AB  - Isolated congenital absence of the alar cartilages and nasal septum is rarely
      reported. We report here an example for the phenotype of carbamazepine
      embryopathy with lower lateral cartilage hypoplasia and our surgical approach to
      solve the nasal problems. This unusual presentation and the literature
      surrounding infant nasal surgery are discussed.

PMID- 21905918
TI  - TBX22 and tongue-tie.
AB  - OBJECTIVE: To resolve if TBX22 mutations cause isolated tongue-tie in the Finnish
      population. DESIGN: Mutation analysis of the coding region of the TBX22 gene in
      50 Finnish isolated tongue-tie patients and 61 control samples. RESULTS: One
      putative sequence variation was identified from two male patients, but whether
      this represents a polymorphism or causative mutation remains unknown.
      CONCLUSIONS: Mutations in the coding region of the TBX22 gene are not a major
      cause of ankyloglossia in the Finnish population and do not explain the sex
      difference or inheritance of tongue-tie.

PMID- 21905919
TI  - Tumor-conditioned mesenchymal stem cells display hematopoietic differentiation
      and diminished influx of Ca2+.
AB  - Mesenchymal stem cells (MSCs) that are present in many adult tissues can generate
      new cells either continuously or in response to injury/cancer. An increasing
      number of studies demonstrated that MSCs have the ability to differentiate into
      cells of mesodermal origin and transdifferentiate into cells such as hepatocytes,
      neural cells. There has been growing interest in the application of MSCs to
      cancer therapy. The relationship between MSCs and cancer cells remains highly
      controversial. In this study, we analyzed the interaction of bone marrow-derived
      MSCs and cancer cells by cell-cell contact and transwell culture system. The flow
      cytometry and real-time polymerase chain reaction showed that after coculture of
      MSCs and cancer cells, MSCs displayed the hematopoietic cell markers such as
      CD34, CD45, and CD11b. The CD68, MRCI, and CSF1R were dramatically upregulated
      after coculture. The cytokine array showed that MSCs after coculture secreted
      monokines and chemokines much more than that of intact MSCs. The MSCs under tumor
      conditions were responsive to stimulation with lipopolysaccharide by cytokines
      release. The tumor-conditioned MSCs showed phagocytic ability and enhanced
      release of nitric oxide, which are the characteristics of macrophages. Calcium
      ion is an important intracellular messenger responsible for differentiation and
      gene expression regulations. The influx of Ca(2+) into MSCs was obviously reduced
      after coculture. The blocking of calcium channel with verapamil obviously
      increased the expression of CD34, CD45, and CD11b, thus indicating that the
      diminished calcium ion influx is coupled with the hematopoietic differentiation
      of MSCs under tumor conditions. Taken together, in a cancer environment, MSCs
      could effectively differentiate into immune hematopoietic cells, precisely
      macrophages. Diminished transient influx of Ca(2+) may mediate the hematopoietic
      differentiation of MSCs.

PMID- 21905920
TI  - Amniotic fluid stem cells increase embryo survival following injury.
AB  - Although amniotic fluid cells can differentiate into several mesenchymal lineages
      and have been proposed as a valuable therapeutic cell source, their ability to
      undergo terminal neuronal differentiation remains a cause of controversy. The aim
      of this study was to investigate the neuronal differentiation ability of the c
      Kit-positive population from GFP-transgenic rat amniotic fluid, amniotic fluid
      stem (AFS) cells, and to assess how they affected injury response in avian
      embryos. AFS cells were found to express several neural stem/progenitor cell
      markers. However, no overt neuronal differentiation was apparent after either
      treatment with small molecules known to stimulate neuronal differentiation,
      attempts to differentiate AFS cell-derived embryoid body-like structures, or
      grafting AFS cells into environments known to support neuronal differentiation
      (organotypic rat hippocampal cultures, embryonic chick nervous system).
      Nonetheless, AFS cells significantly reduced hemorrhage and increased survival
      when grafted at the site of an extensive thoracic crush injury in E2.5 chick
      embryos. Increased embryo survival was induced neither by desmopressin treatment,
      which also reduced hemorrhage, nor by grafting other mesenchymal or neural cells,
      indicating a specific effect of AFS cells. This was found to be mediated by
      soluble factors in a transwell coculture model. Altogether, this study shows that
      AFS cells reduce tissue damage and increase survival in injured embryos,
      providing a potentially valuable tool as therapeutic agents for tissue repair,
      particularly prenatal/perinatal repair of defects diagnosed during gestation, but
      this effect is mediated via paracrine mechanisms rather than the ability of AFS
      cells to fully differentiate into neuronal cells.

PMID- 21905921
TI  - Primitive stem cells derived from bone marrow express glial and neuronal markers
      and support revascularization in injured retina exposed to ischemic and
      mechanical damage.
AB  - Ischemic or mechanical injury to the optic nerve is an irreversible cause of
      vision loss, associated with limited regeneration and poor response to
      neuroprotective agents. The aim of this study was to assess the capacity of adult
      bone marrow cells to participate in retinal regeneration following the induction
      of anterior ischemic optic neuropathy (AION) and optic nerve crush (ONC) in a
      rodent model. The small-sized subset of cells isolated by elutriation and lineage
      depletion (Fr25lin(-)) was found to be negative for the neuroglial markers nestin
      and glial fibrillary acidic protein (GFAP). Syngeneic donor cells, identified by
      genomic marker in sex-mismatched transplants and green fluorescent protein,
      incorporated into the injured retina (AION and ONC) at a frequency of 0.35%-0.45%
      after intravenous infusion and 1.8%-2% after intravitreous implantation.
      Perivascular cells with astrocytic morphology expressing GFAP and vimentin were
      of the predominant lineage that engrafted after AION injury; 10%-18% of the donor
      cells incorporated in the retinal ganglion cell layer and expressed NeuN, Thy-1,
      neurofilament, and beta-tubulin III. The Fr25lin(-) cells displayed an excellent
      capacity to migrate to sites of tissue disruption and developed coordinated site
      specific morphological and phenotypic neural and glial markers. In addition to
      cellular reconstitution of the injured retinal layers, these cells contributed to
      endothelial revascularization and apparently supported remodeling by secretion of
      insulin-like growth factor-1. These results suggest that elutriated autologous
      adult bone marrow-derived stem cells may serve as an accessible source for
      cellular reconstitution of the retina following injury.

PMID- 21905922
TI  - Thymidylate synthase inhibitors for non-small cell lung cancer.
AB  - INTRODUCTION: The folate-dependent enzyme thymidylate synthase (TS) plays a
      pivotal role in DNA replication/repair and cancer cell proliferation, and
      represents a valid target for the treatment of several tumor types, including
      NSCLC. NSCLC is the leading cause of cancer-related mortality, and several TS
      inhibitors have gone into preclinical and clinical testing, with pemetrexed
      emerging for its approval and widespread use as first-/second-line and
      maintenance therapy for this disease. AREAS COVERED: This review summarizes the
      therapeutic options in NSCLC, as well as the background and rationale for
      targeting TS. The authors also review recent pharmacogenetic studies and data
      from clinical trials evaluating novel TS inhibitors, hoping that the reader will
      gain a comprehensive overview of the field of TS inhibition, specifically
      relating to drugs used or being developed for lung cancer patients. EXPERT
      OPINION: TS is a validated target in NSCLC. However, benefits from conventional
      chemotherapy in NSCLC have plateaued, and more cost-effective results should be
      obtained with individualized treatment. Accordingly, the clinical success for TS
      inhibitors may depend on our ability to correctly administer these agents
      following biomarker-driven patient selection, including TS genotype and
      expression, and using the right combination therapy.

PMID- 21905942
TI  - Ease of use and preference of a new versus widely available prefilled insulin pen
      assessed by people with diabetes, physicians and nurses.
AB  - OBJECTIVE: FlexTouch(r) (FT; Novo Nordisk A/S, Bagsvaerd, Denmark) is a new
      prefilled insulin pen that has no push-button extension and low injection force.
      This multi-centre, crossover usability study evaluated the perceptions of, and
      preference for, FT versus another widely used prefilled pen, SoloStar(r) (SS;
      Sanofi, Paris, France), by people with diabetes and healthcare professionals.
      RESEARCH DESIGN AND METHODS: Following instruction, participants performed
      injections into a foam cushion, randomly alternating between doses of 20, 40 and
      80 international units (IU). Participants then answered questions on usability
      and preference. RESULTS: In all, 59 people with diabetes and 61 healthcare
      professionals (30 physicians and 31 nurses) took part. Overall, significantly
      more respondents preferred to use FT than SS (83 vs 10%, respectively), found FT
      easier to use (83 vs 9%) and would recommend FT to others (83 vs 8%; p < 0.001
      for all). More respondents found it 'very/fairly easy' to reach the push-button
      and to inject 20, 40 and 80 IU with FT (93, 90 and 88% to inject, respectively)
      than with SS (73, 43 and 15% to inject, respectively; p < 0.001 for all). Most
      respondents chose FT as giving them the most confidence in correct and complete
      insulin delivery (76 vs 6%; p < 0.001) and considerably more were 'very/rather
      confident' in managing their daily insulin injections with FT than with SS (88 vs
      58%). CONCLUSIONS: Most participants rated FT as easier to use and to inject
      with, were more confident in its accuracy of insulin delivery and preferred it to
      SS.

PMID- 21905943
TI  - Emerging drugs which target the renin-angiotensin-aldosterone system.
AB  - INTRODUCTION: The renin-angiotensin-aldosterone system (RAAS) is already the most
      important target for drugs in the cardiovascular system. However, still new
      developments are underway to interfere with the system on different levels. AREAS
      COVERED: The novel strategies to interfere with RAAS aim to reduce the synthesis
      of the two major RAAS effector hormones, angiotensin (Ang) II and aldosterone, or
      interfere with their receptors, AT1 and mineralocorticoid receptor, respectively.
      Moreover, novel targets have been identified in RAAS, such as the (pro)renin
      receptor, and molecules, which counteract the classical actions of Ang II and are
      therefore beneficial in cardiovascular diseases. These include the AT2 receptor
      and the ACE2/Ang-(1-7)/Mas axis. The search for drugs activating these tissue
      protective arms of RAAS is therefore the most innovative field in RAAS
      pharmacology. EXPERT OPINION: Most of the novel pharmacological strategies to
      inhibit the classical RAAS need to prove their superiority above the existing
      treatment in clinical trials and then have to compete against these now quite
      cheap drugs in a competitive market. The newly discovered targets have functions
      beyond the cardiovascular system opening up novel therapeutic areas for drugs
      interfering with RAAS components.

PMID- 21905944
TI  - Impact of galactomannan testing on the prevalence of invasive aspergillosis in
      patients with hematological malignancies.
AB  - Galactomannan (GM) is a polysaccharide component of the cell wall of Aspergillus
      spp. and is released into the host's circulation by growing hyphae. GM testing of
      patients with hematological malignancies has been rarely considered in recent
      epidemiologic studies of invasive mould infections (IMIs). The aim of the
      investigation was to analyze the impact of GM testing on the reported prevalence
      of IMI by comparing detection rates of IMI before and after the introduction of
      this diagnostic procedure. Prevalence of IMI was assessed by conducting a
      prospective single-centre study over seven months in 2010. Results obtained were
      then compared to those obtained with a representative collection of patients
      assessed by the same investigators at the same institution over seven months in
      2007, i.e., prior to the introduction of GM testing. We found that, in general,
      detection rates of invasive aspergillosis (IA) and invasive mould infections
      increased significantly after the introduction of GM analysis. This study may
      therefore indicate that GM testing has a significant impact on the reported
      prevalence of IMI. Broad usage of such testing in patients with hematological
      malignancies may be able to produce a realistic picture of IMI rates when current
      diagnostic criteria are applied.

PMID- 21905945
TI  - Opportunistic fungal infections in the Asia-Pacific region.
AB  - With more than half the world's population, many Asia-Pacific countries still
      lack resources for adequate infection control and diagnostics. Opportunistic
      invasive fungal infections (IFIs) have a significant impact on public health in
      the region, and early diagnosis and appropriate treatment remain important. The
      incidence of IFI in the Asia-Pacific region is increasing because of the expanded
      population of immunosuppressed patients resulting from advances in medical
      technology, such as treatments for cancer and transplantation, as well as the
      impact of human immunodeficiency virus. Even so, the epidemiology of IFIs is not
      well described in the Asia-Pacific region. Prevalence of some infections, such as
      mucormycosis, is particularly related to undiagnosed or untreated diabetes, which
      is likely to be a continuing problem with the epidemic of diabetes in the region.
      In addition, despite some effective treatment options, IFIs are associated with
      high morbidity and mortality. In an attempt to increase recognition of invasive
      mycoses in this large area, this paper reviews recent findings on the
      epidemiology of the most clinically significant opportunistic mould and yeast
      infections in the Asia-Pacific region, i.e., aspergillosis, mucormycosis,
      pythiosis, scedosporiosis, fusariosis, candidiasis, trichosporonosis, and
      cryptococcosis.

PMID- 21905946
TI  - Detection of invasive infection caused by Fusarium solani and non-Fusarium solani
      species using a duplex quantitative PCR-based assay in a murine model of
      fusariosis.
AB  - A duplex Real Time PCR (RT-PCR) assay for detecting DNA of members of the genus
      Fusarium has been developed and validated by using two mouse models of invasive
      infection. The duplex RT-PCR technique employed two specific molecular beacon
      probes targeting a highly conserved region of the fungal rDNA gene. This
      technique showed a detection limit of 10 fg DNA per MUl of sample and a
      specificity of 100%. The sensitivity in a total of 48 samples from a murine model
      of Fusarium solani infection was 93.9% for lung tissues and 86.7% for serum
      samples. In comparison, the sensitivity in a total of 45 samples of a F.
      oxysporum murine model infection was 87% for lung tissues and 42.8% for serum
      samples. This molecular technique could be a reliable method for the
      quantification and the evaluation of the disease in animal models and for the
      clinical diagnosis of fusariosis.

PMID- 21905947
TI  - Candidal thrombophlebitis of central veins: case report and review.
AB  - Although candidemia and central catheter septic thrombosis is quite common,
      central veins thrombophlebitis caused by Candida spp. is a rarely reported
      complication in critically ill patients. Here we report a case of
      thrombophlebitis of the right internal jugular and subclavian veins due to
      Candida albicans which occurred in a patient admitted in the intensive care unit
      for major trauma. The individual was eventually cured after prolonged course of
      antifungal therapy. We also review 24 additional cases of Candida induced central
      veins thrombophlebitis reported since 1978. A central vein catheter was in place
      in all 25 patients with 21 (84%) being admitted in an intensive care unit, 22
      (88%) were receiving total parenteral nutrition and 23 (92%) undergoing a course
      of antibiotic therapy. Overall mortality was 16%, including two patients who
      received no therapy and died. In the group of patients receiving only medical
      therapy, the mortality rate was 13%, while no deaths were observed among those
      treated with combined medical and surgical therapy. Literature data suggest that
      Candida caused central veins thrombophlebitis is a rare and probably
      underdiagnosed infectious complication of the critically ill patient. Despite the
      dramatic presentation with persistent candidemia, mortality is low even with a
      conservative medical approach with prolonged fungicidal therapy through the use
      of amphotericin B or echinocandins. Thus, the decision for a combined surgical
      debridement should be assessed for each patient.

PMID- 21905948
TI  - Epidemiological analysis of worldwide bovine, canine and human clinical
      Prototheca isolates by PCR genotyping and MALDI-TOF mass spectrometry proteomic
      phenotyping.
AB  - This study presents information on the phenotypic and genotypic characterization
      of clinical Prototheca spp. isolates obtained from different geographic regions.
      Of 350 isolates studied, 342 came from cattle, six from canines and two from
      humans. Phenotypic characterization was carried out by a matrix-assisted laser
      desorption/ionization-time of flight (MALDI-TOF) proteomic analysis. The peptide
      extraction that was used for this analysis included the additional steps of
      washing and sonication to increase the yield of peptide. Genotypic analysis was
      conducted using species- and genotype-specific primers. The study revealed that
      among the cattle isolates, 310 (90.6%) belonged to Prototheca zopfii genotype 2,
      30 (8.8%) to P. blaschkeae, and two (0.6%) to P. zopfii genotype 1. P. zopfii
      genotype 2 is the principal etiological agent of protothecal mastitis in cattle
      regardless of the geographic region. Similarly, all canine and human isolates
      also belonged to the P. zopfii genotype 2, suggesting that this is probably the
      most virulent species of the genus. The role of P. blaschkeae needs further
      epidemiologic studies to ascertain its etiologic role in bovine mastitis. To the
      best of our knowledge, this is the first comprehensive study on phenotypic and
      genotypic characterization of P. zopfii and P. blaschkeae isolates originating
      from diverse clinical specimens from different countries.

PMID- 21905949
TI  - Trichophyton bullosum: a new zoonotic dermatophyte species.
AB  - We report the first human case of dermatophytosis caused by Trichophyton bullosum
      in a 21-year-old male who had a skin lesion located on his forearm. The
      dermatophyte was isolated in culture and further identified by sequence analysis
      of internal transcripted spacer regions.   The species T. bullosum is a zoophilic
      dermatophyte rarely isolated from the coat of horses in Africa and Asia. In the
      present case, it was probably transmitted by contact with an infected donkey in a
      rural area in France. Antifungal therapy led to remission of the lesion in the
      patient after 2 months of treatment. T. bullosum ITS region sequences were
      closely related to those of the African species of Arthroderma benhamiae and
      grouped in a zoophilic cluster with Trichophyton verrucosum, T. erinacei and the
      Trichophyton anamorph of A. benhamiae (zoophilic species of the T. mentagrophytes
      complex). Systematic molecular identification could contribute to an accurate
      identification of this unusual species.

PMID- 21905950
TI  - Distribution of yeast species associated with oral lesions in HIV-infected
      patients in Southwest Uganda.
AB  - Oropharyngeal candidiasis remains a significant clinical problem in HIV-infected
      and AIDS patients in regions of Africa where anti-retroviral therapy isn't
      readily available. In this study we identified the yeast populations associated
      with oral lesions in HIV-infected patients in Southwest Uganda who were receiving
      treatment with nystatin and topical clotrimazole. Samples were taken from 605
      patients and 316 (52%) of these yielded yeast growth following incubation on
      Sabouraud dextrose agar. Samples were subsequently re-plated on CHROMagar Candida
      medium to facilitate identification of the yeast species present. The majority
      (56%) of culture-positive samples yielded a mix of two or more species. Candida
      albicans was present in 87% (274/316) of patient samples and accounted for 87%
      (120/138) of single species samples. Candida glabrata, Candida tropicalis and
      Candida norvegensis were also found in cultures that yielded a single species. No
      Candida dubliniensis isolates were identified in this population.

PMID- 21905951
TI  - Vogt-Koyanagi-Harada syndrome: a rare but important differential diagnosis of
      viral meningitis.
AB  - Vogt-Koyanagi-Harada syndrome (VKHS) is an inflammatory syndrome affecting
      melanocyte-containing organs. The clinical onset is often acute with neurological
      and ophthalmological symptoms and there is considerable risk of sequelae if the
      condition is not promptly diagnosed and treated. We present a case illustrating
      that VKHS is a rare but important differential diagnosis of viral meningitis.

PMID- 21905952
TI  - Hepatitis C virus infection prevalence and liver dysfunction in a cohort of B
      cell non-Hodgkin's lymphoma patients treated with immunochemotherapy.
AB  - Several studies have reported a higher prevalence of hepatitis C virus (HCV)
      infection in patients with B-cell non-Hodgkin's lymphoma (NHL) than in the
      general population. Treatment for NHL includes the use of chemotherapeutic agents
      such as cytotoxic drugs, corticosteroids, and rituximab, which can be
      immunosuppressive and hepatotoxic. While reactivation of hepatitis B virus (HBV)
      when undergoing immunosuppressive therapy for haematological malignancies is a
      well-documented complication, data on HCV reactivation or liver function
      impairment after chemotherapy for NHL are controversial. From January 2006 to
      December 2009, 207 consecutive NHL patients treated with chemotherapy without
      rituximab (CHOP) or with rituximab (R-CHOP) were observed; screening for HCV
      infection and baseline liver function tests were performed in all patients. The
      prevalence of HCV infection was 9.2%. This prevalence is higher than that
      observed in the general population in Italy (3%). Among the HCV-infected
      subjects, the incidence of hepatitis flares was 26.3% vs 2.1% among the HCV
      uninfected individuals. Although less frequent and less severe than in HBV
      infected subjects, liver dysfunction can occur as a consequence of rituximab
      containing regimens in HCV-infected patients with NHL. In the cases considered in
      this study, no patient treated with chemotherapy without rituximab developed
      hepatitis flares. The frequency and the severity of this complication vary in
      different reports. Therefore, we recommend the assessment of liver function and
      the screening of all patients with NHL for HCV infection before starting
      chemotherapy; we also recommend monitoring of liver function tests and HCV-RNA
      serum levels during treatment.

PMID- 21905953
TI  - Lack of correlation between the 257C-to-T mutation in the gyrA gene and clinical
      severity of Campylobacter jejuni infection in a region of high incidence of
      ciprofloxacin resistance.
AB  - BACKGROUND: Fluoroquinolone resistance is increasingly detected in Campylobacter
      jejuni worldwide. Despite the fact that a point mutation in the gyrA gene has
      been linked with increased fitness in animals, the association of resistant
      organisms with more severe infections in man remains controversial. METHODS:
      Erythromycin and quinolone susceptibility of 147 C. jejuni strains isolated from
      individual patients with diarrhoea in southwest Hungary were investigated and the
      molecular background of fluoroquinolone resistance was determined.
      Hospitalization and the presence of macroscopic blood in the stool were
      correlated with the presence of 257C-to-T mutation of the gyrA gene causing
      resistance to fluoroquinolones. RESULTS: Isolates showed an extensive genetic
      heterogeneity by macrorestriction analysis of the chromosome. While all strains
      retained susceptibility to erythromycin, 68% were non-susceptible to
      ciprofloxacin. The mutation causing a Thr-86-to-Ile replacement in the gyrA gene
      was present in 98% of non-susceptible isolates. Infection caused by isolates
      containing this mutation did not show any significant association with either
      hospitalization or with the development of bloody diarrhoea. CONCLUSIONS: Our
      findings indicate that in a region with high-level ciprofloxacin resistance in C.
      jejuni, non-susceptibility to this antibiotic did not correlate with the severity
      of infection.

PMID- 21905954
TI  - Mesenchymal stromal cells derived from CD271(+) bone marrow mononuclear cells
      exert potent allosuppressive properties.
AB  - BACKGROUND AIMS. Because data on the immunosuppressive effect of different
      subsets of mesenchymal stromal cells (MSC) are sparse, we investigated the
      molecular and cellular mechanisms underlying the allosuppressive effect of MSC
      generated from bone marrow CD271(+) cells (CD271-MSC) and asked whether this
      potential is comparable with that of MSC generated through plastic adherence (PA
      MSC). METHODS. The immunosuppressive effect of CD271-MSC on the allogeneic
      reaction was investigated by mixed lymphocyte reaction (MLR). RESULTS. CD271-MSC
      significantly suppressed the alloantigen-induced proliferation of mononuclear
      cells (MNC) of two HLA-disparate donors at all MSC:MNC ratios, 1:1, 1:2 and 1:10.
      They also demonstrated a significantly higher allosuppression than PA-MSC at an
      MSC:MNC ratio of 1:1. This inhibitory effect was associated with significantly
      elevated levels of prostaglandin E2 (PGE2) at ratios of 1:1 and 1:2 (about 4
      fold), but not at a ratio of 1:10. Indomethacin, and inhibitor of cyclooxygenase
      1 and 2 necessary for the biosynthesis of PGE2, mitigated suppressive effects of
      CD271-MSC only at a ratio of 1:1, indicating that PGE2 is not involved in MSC
      mediated inhibition when allogeneic MNC are in excess. The increase of PGE2 was
      associated with a significant decrease of pro-inflammatory cytokine levels
      (interferon-gamma and tumor necrosis-alpha), while no changes in levels of
      interleukin-10, soluble HLA-G and nitric oxide were observed. In addition, CD271
      MSC induced an expansion of highly suppressive naive
      CD4(+)CD25(high)CD45RA(+)CD62L(+) T-regulatory cells, which may extend their
      allosuppressive effect. CONCLUSIONS. Our data suggest that CD271-MSC exert potent
      allosuppressive properties and therefore can be used as a reasonable alternative
      to PA-MSC for the treatment of patients with graft-versus-host disease.

PMID- 21905955
TI  - Effects of peripheral blood stem cell apheresis on systemic cytokine levels in
      patients with multiple myeloma.
AB  - BACKGROUND AIMS. Pro-angiogenic cytokines can affect myeloma cell proliferation
      directly and indirectly through stimulation of cancer-associated angiogenesis.
      METHODS. We investigated how peripheral blood stem cell (PBSC) collection
      affected plasma angioregulatory cytokine levels in 15 consecutive myeloma
      patients. RESULTS. Plasma levels of hepatocyte growth factor (HGF) were
      significantly increased prior to apheresis in patients compared with donors, and
      a further increase was detected immediately after PBSC apheresis. HGF levels
      decreased within 24 h, but were still higher than the levels in healthy donors,
      whose HGF levels were not altered by platelet apheresis. Pre-apheresis levels of
      other angioregulatory cytokines, angiopoietin-2 and vascular endothelial growth
      factor (VEGF), were also increased in patients, whereas angiopoietin-1,
      angiogenin and basic fibroblast growth factor levels did not differ from healthy
      controls. PBSC harvesting decreased angiopoietin-1 and VEGF levels, increased the
      microvascular endothelial cell marker endocan levels but did not affect the other
      mediators. CONCLUSIONS. Our results show that PBSC apheresis alters systemic
      angioregulatory profiles in myeloma patients. This cytokine modulation is not a
      general characteristic of all apheresis procedures and was not seen in healthy
      platelet donors.

PMID- 21905956
TI  - Immunoregulatory effects of human dental pulp-derived stem cells on T cells:
      comparison of transwell co-culture and mixed lymphocyte reaction systems.
AB  - BACKGROUND AIMS. Studies performed using human and animal models have indicated
      the immunoregulatory capability of mesenchymal stromal cells in several lineages.
      We investigated whether human dental pulp-derived stem cells (hDP-SC) have
      regulatory effects on phytohemagglutinin (PHA)-activated CD3(+) T cells. We aimed
      to define the regulatory mechanisms associated with hDP-SC that occur in mixed
      lymphocyte reaction (MLR) and transwell systems with PHA-CD3(+) T cells and hDP
      SC at a ratio of 1:1. METHODS. Proliferation, apoptosis and pro- and anti
      inflammatory cytokines of PHA-CD3(+)T cells, the expression of Regulatory T cells
      (Treg) markers and some regulatory factors related to hDP-SC, were studied in
      Both transwell and MLR are co-cultures systems. RESULTS. Anti-proliferative and
      apoptotic effects of hDP-SC were determined in co-culture systems. Elevated
      expression levels of human leukocyte antigen (HLA)-G, hepatocyte growth factor
      (HGF)-beta1, intracellular adhesion molecule (ICAM-1)-1, interleukin (IL)-6, IL
      10, transforming growth factor (TGF)-beta1, vascular adhesion molecule (VCAM)-1
      and vascular endothelial growth factor (VEGF) by hDP-SC were detected in the co
      culture systems. We observed decreased expression levels of pro-inflammatory
      cytokines [interferon (IFN)-gamma, IL-2, IL-6 receptor (R), IL-12, Interleukin
      17A (IL-17A), tumor necrosis factor (TNF)-alpha] and increased expression levels
      of anti-inflammatory cytokine [inducible protein (IP)-10] from PHA-CD3(+) T cells
      in the transwell system. Expression of Treg (CD4(+) CD25(+) Foxp3(+)) markers was
      significantly induced by hDP-SC in both co-culture systems. We observed apoptosis
      of PHA-CD3(+) T cells with 24 h using time-lapse camera photographs and active
      caspase labeling; it is likely that paracrine soluble factors and molecular
      signals secreted by hDP-SC led this apoptosis. CONCLUSIONS. We suggest that hDP
      SC have potent immunoregulatory functions because of their soluble factors and
      cytokines via paracrine mechanisms associated with PHA-CD3(+) T cells, which
      could contribute to clinical therapies.

PMID- 21905957
TI  - Aldehyde dehydrogenase as an alternative to enumeration of total and viable
      CD34(+) cells in autologous hematopoietic progenitor cell transplantation.
AB  - We validated the correlation of aldehyde dehydrogenase ALDH(br) cells with total
      and viable CD34(+) cells in fresh and thawed hematopoietic progenitor cell (HPC)
      products, and looked for a correlation with time to white blood cell (WBC) and
      platelet engraftment after autologous transplantation, using simple linear
      regression analyzes. We found a significant correlation between pre-freeze
      ALDH(br) cell numbers and pre-freeze total CD34(+) (P < 0.001), viable CD34(+) (P
      < 0.001) and post-thaw viable CD34(+) (P < 0.001) cell numbers. We suggest that
      ALDH(br) may be substituted for CD34(+) cell numbers when evaluating HPC. As post
      thaw viability testing apparently adds no significant information, we suggest
      that it may not be necessary. Finally, neither marker correlated with time to
      engraftment in our patients, supporting previous data suggesting the existence of
      a threshold dose for timely engraftment around 2.5 * 10(6) cells/kg.

PMID- 21905958
TI  - Development and validation of a procedure to isolate viable bone marrow cells
      from the vertebrae of cadaveric organ donors for composite organ grafting.
AB  - BACKGROUND AIMS: Donor-derived vertebral bone marrow (BM) has been proposed to
      promote chimerism in solid organ transplantation with cadaveric organs. Reports
      of successful weaning from immunosuppression in patients receiving directed donor
      transplants in combination with donor BM or blood cells and novel peri-transplant
      immunosuppression has renewed interest in implementing similar protocols with
      cadaveric organs. METHODS: We performed six pre-clinical full-scale separations
      to adapt vertebral BM preparations to a good manufacturing practice (GMP)
      environment. Vertebral bodies L4-T8 were transported to a class 10 000 clean
      room, cleaned of soft tissue, divided and crushed in a prototype bone grinder.
      Bone fragments were irrigated with medium containing saline, albumin, DNAse and
      gentamicin, and strained through stainless steel sieves. Additional cells were
      eluted after two rounds of agitation using a prototype BM tumbler. RESULTS: The
      majority of recovered cells (70.9 +/- 14.1%, mean +/- SD) were eluted directly
      from the crushed bone, whereas 22.3% and 5.9% were eluted after the first and
      second rounds of tumbling, respectively. Cells were pooled and filtered (500, 200
      MUm) using a BM collection kit. Larger lumbar vertebrae yielded about 1.6 times
      the cells of thoracic vertebrae. The average product yielded 5.2 +/- 1.2 * 10(10)
      total cells, 6.2 +/- 2.2 * 10(8) of which were CD45(+) CD34(+). Viability was
      96.6 +/- 1.9% and 99.1 +/- 0.8%, respectively. Multicolor flow cytometry revealed
      distinct populations of CD34(+) CD90(+) CD117(dim) hematopoietic stem cells (15.5
      +/- 7.5% of the CD34 (+) cells) and CD45(-) CD73(+) CD105(+) mesenchymal stromal
      cells (0.04 +/- 0.04% of the total cells). CONCLUSIONS: This procedure can be
      used to prepare clinical-grade cells suitable for use in human
      allotransplantation in a GMP environment.

PMID- 21905959
TI  - Powered-assisted partial turbinectomy versus mometasone furoate nasal spray for
      relief of nasal blockage in chronic or idiopathic rhinosinusitis.
AB  - CONCLUSION: Power-assisted turbinectomy is a safe and reliable alternative for
      patients with nasal blockage if nasal corticosteroid spray therapy is not
      suitable. OBJECTIVE: Powered-assisted partial turbinectomy was compared to the
      use of a corticosteroid nasal spray for relief of nasal obstruction in chronic or
      idiopathic rhinosinusitis. METHODS: Patients were randomized to either power
      assisted partial turbinectomy or daily use of mometasone furoate nasal spray for
      6 months. Evaluation by peak nasal inspiratory flow (PNIF) and grading of
      symptoms by use of visual analog scale was done after 3 and 6 months. Grading of
      symptoms was also done by use of a questionnaire approximately 30 months after
      the last visit. RESULTS: PNIF scores improved for all patients, although
      significantly only for patients on mometasone spray. Patients' self-reported
      symptoms decreased more for operated patients. Side effects were few and mild in
      both groups.

PMID- 21905960
TI  - Comparison of the distribution pattern of PEG-b-PCL polymersomes delivered into
      the rat inner ear via different methods.
AB  - CONCLUSION: Cochleostomy is the most efficient approach in delivering PEG-b-PCL
      polymersomes (PMs) to the inner ear. PMs can be delivered to the vestibule by
      transtympanic injection or cochleostomy. OBJECTIVE: To evaluate the efficiency of
      delivering PEG-b-PCL PMs into the inner ear using different approaches. METHODS:
      The PEG-b-PCL PMs were administered either by sustained topical round window
      membrane (RWM) delivery using gelatin sponge pledgets in combination with an
      osmotic pump, transtympanic injection, or cochleostomy. The distribution of the
      PMs in the inner ear was observed by confocal microscopy using either whole mount
      specimens or cryosections. RESULTS: Cochleostomy resulted in distribution of the
      PMs in the spiral ligament (SL), mesothelial cells beneath the organ of Corti,
      supporting cells in the organ of Corti, and spiral ganglion cells (SGCs).
      Transtympanic injection induced uptake of the PMs in the SL and mesothelial cells
      beneath the organ of Corti. Topical administration showed distribution of the PMs
      only in the SL. In the vestibulum, transtympanic injection and cochleostomy
      induced more distribution of the PMs than did topical RWM delivery (p < 0.05,
      Kruskal-Wallis test).

PMID- 21905961
TI  - Immunohistochemical localization of transforming growth factor beta1 and beta2 in
      mouse testes during postnatal development.
AB  - We examined age-related changes in the expression of transforming growth factor
      beta(1) (TGF-beta(1)) and transforming growth factor-beta(2) in mouse testes. The
      mice were assigned to three age groups: 35, 50, and 75 days old. Paraffin
      embedded testis sections were processed for the standard streptavidin biotin
      peroxidase complex immunohistochemistry method. TGF-beta(1) expression increased
      in aging round spermatids over the time studied. There was no expression in 35
      day-old Leydig cells, whereas strong expression of TGF-beta(1) was observed in 50
      day-old Leydig cells. Expression decreased in 75-day-old Leydig cells. TGF
      beta(2) expression was weak in 35- and 50-day-old mouse spermatids, but
      expression was greater in 75-day-old elongated spermatids. In Leydig cells, TGF
      beta(2) expression was strong in both 35- and 50-day-old mice, whereas the
      expression of TGF-beta(2) was less in 75-day-old Leydig cells. Our results
      suggest that TGF-beta(1) and TGF-beta(2) may play significant roles in testicular
      functions and germ cell development in mice.

PMID- 21905962
TI  - A new technique for visualizing proanthocyanidins by light microscopy.
AB  - We describe a new technique for visualizing proanthocyanidin-containing elements
      in plant tissues. Our innovation is the fixation of condensed tannins with an
      exogenous protein prior to alcohol dehydration. In this way, tannins do not
      undergo partial solubilization during the dehydration sequence and appear as
      sharply contoured globules of various diameters.

PMID- 21905963
TI  - Gefitinib for non-small-cell lung cancer treatment.
AB  - INTRODUCTION: Gefitinib is an EGFR tyrosine kinase inhibitor (EGFR-TKI) that
      demonstrated efficacy in patients with advanced non-small cell lung cancer
      (NSCLC) across therapy lines. In the first-line setting, recent randomized Phase
      III trials comparing EGFR-TKIs versus platinum-based doublets demonstrated that
      in patients harboring an activating EGFR mutation, gefitinib is superior to
      chemotherapy in terms of response rate, progression-free survival, toxicity
      profile and quality of life, with a marginal positive effect on survival. In
      order to choose the best treatment, a molecular characterization is now
      mandatory, as part of baseline diagnostic procedures. AREAS COVERED: All
      published data on gefitinib in lung cancer were analyzed using PubMed. The aim of
      this review is to summarize activity and safety data from major clinical trials
      of gefitinib in patients with advanced NSCLC. EXPERT OPINION: EGFR-TKIs including
      gefitinib are the best option we can offer today in patients with EGFR mutation,
      regardless of treatment line. Administration of gefitinib to patients with
      advanced NSCLC is usually well-tolerated and it also appears to be feasible in
      special populations characterized by a significantly poorer risk:benefit ratio
      with standard chemotherapy, like elderly patients and patients with poor
      performance status.

PMID- 21905964
TI  - Neoteric pharmacotherapeutic targets in fibromyalgia.
AB  - INTRODUCTION: Fibromyalgia is a debilitating, chronic pain disorder typically
      present with allodynia and hyperalgesia. Estimates from the USA suggest that
      fibromyalgia affects about 5% of women, and is the third most common rheumatic
      disorder after lower back pain and osteoarthritis. Recent research advances
      highlighted a role for aberrant central pain processing in fibromyalgia, and
      consistent with this, the first three drugs (pregabalin, duloxetine and
      milnacipran) approved by the FDA for fibromyalgia over the past 2 years have a
      predominantly central mode of action. Despite progress in understanding of
      fibromyalgia and the long-awaited introduction of three medications for treating
      it, fibromyalgia continues to pose a significantly unmet medical need, negatively
      affecting the lives of millions of individuals worldwide in all ethnic groups and
      all economic classes. AREAS COVERED: Prevailing theories of pathogenesis of
      fibromyalgia, existing therapies and the potential of current research on novel
      targets. EXPERT OPINION: Current research on novel sedative-hypnotics, anti
      epileptic medications, various reuptake inhibitors, growth hormone agonists,
      canabinoid agonists, non-opiate analgesics and 5-HT3 antagonists offers hope for
      the the next generation of therapeutic options for fibromyalgia. With regards to
      the development of novel pharmacotherapies, there seem to be grounds for
      increased optimism regarding prospective treatments of the disorder.

PMID- 21905965
TI  - Cervical artery dissection: risk factors, treatment, and outcome; a 5-year
      experience from a tertiary care center.
AB  - BACKGROUND: Cervical artery dissection (CAD) is a common cause of stroke in young
      individuals. Risk factors, treatment, and outcome of CAD are not well
      established. Our aim is to identify risk factors, outcome, and discuss treatment
      of CAD. METHODS: We reviewed medical records of patients seen at our institution
      between 2004 and 2009, using ICD-9 codes for CAD, for risk factors, treatment,
      type, and outcome. Poor outcome was defined as modified Rankin Scale (mRS) score
      within 6 months of >1 or recurrent stroke or transient ischemic attack (TIA).
      RESULTS: A total of 47 patients were identified. Twenty-four patients had
      spontaneous dissections (52%); 30 (63%) involved the carotid. As compared with
      spontaneous dissections, traumatic dissections occurred in younger patients (mean
      age 41.0 vs. 47.7 years, p = .064), were more likely to involve the vertebral
      artery (52% vs. 21%, p = .036, and caused less neurological deficits on
      presentation (48% vs. 75%, p = .075). Conversely, spontaneous dissections were
      more likely to occur in patients with hypertension (63% vs. 30%, p = .041) and
      hypercholesterolemia (46% vs. 9%, p = .008). Patients having no stroke had better
      outcomes (100% vs. 54%, p < .001). Anticoagulation was used in 17 patients (36%)
      and antiplatelets in 31 (64%). Outcome and adverse events were similar in the two
      groups. CONCLUSION: Hypertension and hypercholesterolemia were risk factors in
      spontaneous dissections, speaking for vascular wall abnormalities as potential
      contributors to pathophysiology of CAD. There was no evidence supporting one type
      of treatment over the other. A large ongoing prospective study should quell this
      controversy.

PMID- 21905966
TI  - Pharmacokinetic evaluation of pixantrone for the treatment of non-Hodgkin's
      lymphoma.
AB  - INTRODUCTION: Pixantrone is a novel aza-anthracenedione, similar in structure to
      anthracyclines, including the anthracycline derivative mitoxantrone. There is no
      standard therapy for relapsed or refractory aggressive non-Hodgkin's lymphoma
      (NHL) in patients who have received two prior lines of therapy. Pixantrone does
      not bind iron, promotes reactive oxygen species to a lesser degree than other
      anthracyclines and is therefore believed to be less cardiotoxic without
      compromising efficacy. AREAS COVERED: This article outlines the chemical
      properties of pixantrone, as well as the preclinical and clinical studies looking
      at pixantrone in the treatment of both indolent and aggressive NHL. EXPERT
      OPINION: Pixantrone is an active and safe drug that has been shown to be of
      benefit when used to treat patients with relapsed aggressive NHL in the context
      of Phase II and Phase III studies. It was superior to other single-agent
      therapies in this context and in combination therapy may be the treatment of
      choice in order to avoid cardiac toxicity. Potentially it is a more effective and
      less cardiotoxic alternative to doxorubicin in patients with aggressive NHL.

PMID- 21905967
TI  - Efficacy and tolerability of telmisartan plus amlodipine in added-risk
      hypertensive patients.
AB  - OBJECTIVES: Added-risk hypertensive patients with co-morbidities such as diabetes
      and metabolic syndrome often require two or more antihypertensives to achieve
      blood pressure (BP) targets. The aim of this sub-analysis was to determine the
      efficacy and safety of telmisartan 40 or 80 mg plus amlodipine 5 or 10 mg in
      patients with hypertension, stratified according to certain criteria such as type
      2 diabetes mellitus and metabolic syndrome. METHODS: Patients were treated for 8
      weeks with telmisartan 20-80 mg plus amlodipine 2.5-10 mg. This post-hoc analysis
      included patients treated with higher doses, and stratified according to a number
      of sub-populations (age, race, diabetes, obesity, metabolic syndrome, elevated
      baseline systolic BP (SBP), renal impairment). RESULTS: Eight weeks' treatment
      with telmisartan plus amlodipine combinations provided consistent reductions in
      mean SBP/diastolic BP (DBP) across the different sub-populations, similar to the
      overall population. SBP/DBP reductions ranged from -13.5 to -34.7/-12.6 to -26.1
      mmHg and BP goal rates (<140/90 mmHg) ranged from 29.8-100% for the four key dose
      combinations of telmisartan plus amlodipine. For the highest dose combination of
      telmisartan 80 mg plus amlodipine 10 mg, SBP/DBP reduction ranged from -19.1 to 
      34.7/-16.4 to -22.8 mmHg and goal attainment rate from 66.7% to 87.0%. Across the
      sub-populations, high SBP and DBP response rates were seen with combination
      treatment (83.3-97.7% and 75.0-95.7%, respectively, with telmisartan 80 mg plus
      amlodipine 10 mg). The combination was safe and well tolerated across all sub
      populations and the incidence of peripheral oedema with telmisartan 40-80 mg plus
      amlodipine 10 mg was generally lower than with A10 monotherapy. CONCLUSIONS:
      Despite small patient numbers in some sub-populations and the post-hoc nature of
      the analysis, this does show that the combination of telmisartan plus amlodipine
      provides an effective, safe and well-tolerated antihypertensive treatment for
      added-risk hypertensive patients.

PMID- 21905968
TI  - Systematic review of tapentadol in chronic severe pain.
AB  - AIM: A systematic review of chronic pain treatment with strong opioids (step 3
      WHO pain ladder) and a comparison to a new drug recently approved for the
      treatment of severe chronic pain in Europe, tapentadol (Palexia, Nucynta*), were
      performed. METHODS: Thirteen electronic databases were searched as well as a
      number of other sources from 1980 up to November 2010 for relevant randomized
      controlled clinical trials in chronic moderate and severe pain investigating at
      least one step 3 opioid. Chronic pain could be nociceptive or neuropathic,
      malignant or non-malignant, all systemic administrations were considered as well
      as trials of different lengths. Two separate analyses were performed, one only
      for trials which reported (at least as sub-groups) the outcome in patients with
      severe pain, the other including both moderate and severe pain conditions. With
      the exception of the direct comparison between tapentadol, oxycodone and placebo,
      indirect comparisons were performed based on a network analysis. Trials with an
      enriched or an enriched withdrawal design were excluded. Primary (pain intensity)
      and a number of secondary endpoints were evaluated, including pain relief (30%
      and 50%), patient global impression of change, quality of life, quality of sleep,
      discontinuations, as well as serious adverse events and selected adverse events.
      RESULTS: Only 10 trials were eligible for analysis of patients with severe pain
      (eight investigating tapentadol and two trials comparing buprenorphine patch vs
      placebo). For moderate and severe pain, 42 relevant trials were identified and
      indirect comparisons with transdermal buprenorphine, transdermal fentanyl,
      hydromorphone, morphine, and oxymorphone were performed. This report focuses on
      the network analysis. Tapentadol showed statistically favourable results over
      oxycodone for pain intensity, 30% and 50% pain relief, patient global impression
      of change (PGIC), and quality of life. Furthermore, some of the most important
      adverse events of chronic opioid treatment were significantly less frequent with
      tapentadol as compared to oxycodone, i.e. constipation, nausea, and vomiting;
      discontinuations due to these adverse events were found significantly reduced
      with tapentadol. Similar results were obtained for the network analysis, i.e.
      tapentadol was superior for the primary outcome (pain intensity) to hydromorphone
      and morphine, whereas fentanyl and oxymorphone showed trends in favour of these
      treatments. Significantly less frequent gastrointestinal adverse events of
      tapentadol were observed in comparison with fentanyl, hydromorphone, morphine,
      and oxymorphone, apparently leading to significantly reduced treatment
      discontinuations (for any reason). CONCLUSIONS: Taken together, the benefit-risk
      ratio of tapentadol appears to be improved compared to step 3 opioids.

PMID- 21905969
TI  - Single-agent rituximab in treatment-refractory or poor prognosis patients with
      chronic lymphocytic leukemia.
AB  - OBJECTIVE: Rituximab in combination with fludarabine and cyclophosphamide has
      significantly improved outcomes for patients with chronic lymphocytic leukemia
      (CLL) and an improvement in overall survival has recently been shown for the
      first time in the history of CLL treatment. However, the chemotherapy portion of
      this regimen may be unsuitable for elderly patients or those with significant
      comorbidities. We investigated the safety and tolerability of single-agent
      rituximab in 23 consecutive patients presenting with CLL at a single institution.
      RESEARCH DESIGN AND METHODS: Patients received eight cycles of weekly rituximab
      (375 mg/m(2) initially). Patients progressing on rituximab treatment could
      receive up to five further courses of single-agent rituximab in escalating doses
      up to 3 gm/m(2) per dose. Previously untreated and previously treated patients,
      including those refractory to fludarabine, were eligible for the study. RESULTS:
      Single-agent rituximab was efficacious, even in patients with treatment
      refractory or poor-prognosis CLL. The overall response rate was 90.9% with a CR
      rate of 63.6%. The median PFS was 28.5 months, and median duration of response
      was 26 months. Responses were seen regardless of prior treatment including in
      patients refractory to fludarabine. Especially encouraging results were seen in
      patients receiving rituximab maintenance therapy who had a median duration of
      response substantially longer than those who did not receive maintenance (35
      months vs. 14 months, respectively). CONCLUSIONS: Rituximab was well tolerated
      with no unexpected adverse events even at the highest dose. These results
      indicate that single-agent rituximab is effective and has a place in the
      treatment of CLL.

PMID- 21905971
TI  - Renal nerve ablation: emerging role in therapeutics.

PMID- 21905970
TI  - Further assessment of the clinically effective dose range of etoricoxib: a
      randomized, double-blinded, placebo-controlled trial in rheumatoid arthritis.
AB  - OBJECTIVE: To further assess the clinically active dose range of etoricoxib, a
      COX-2 selective inhibitor, in rheumatoid arthritis (RA). METHODS: RA patients
      were randomized to etoricoxib 10, 30, 60, or 90 mg or placebo in a double-blind,
      12-week study. DMARDs (methotrexate, biologics) or low-dose corticosteroids were
      allowed in stable doses. The primary endpoint was the proportion of patients
      completing the study and achieving an American College of Rheumatology 20%
      (ACR20) response. Secondary endpoints included individual components of the ACR
      index and Patient Global Assessment of Pain. Safety was assessed by physical exam
      and adverse experiences (AEs) occurrences. RESULTS: Etoricoxib 90 mg was the only
      dose to reach a statistically significant difference from placebo (p < 0.001) on
      the primary endpoint; etoricoxib 60 mg approached significance (p = 0.057).
      Significant pain improvement vs. placebo was observed with etoricoxib 90 mg (p <
      0.001), 60 mg (p = 0.018), and 30 mg (p = 0.017). Despite the use of background
      biologics and corticosteroids, a dose response was still apparent. A higher
      proportion of etoricoxib 60 and 90 mg patients had renovascular AEs (i.e., edema
      and hypertension) compared with placebo, although discontinuations for
      renovascular AEs were rare. Etoricoxib 90 mg had a higher incidence of serious
      AEs (n = 5; 1 was considered drug-related) versus placebo (n = 0). LIMITATIONS:
      The present study was not powered to detect differences in cardiovascular or
      gastrointestinal safety by dose. Additionally, further research is needed to
      clarify the role of doses less than the etoricoxib 90 mg dose for pain management
      in RA patients. CONCLUSION: Etoricoxib 90 mg demonstrated statistically superior
      efficacy (ACR20) compared with placebo and numerical superiority over the other
      doses of etoricoxib studied. Etoricoxib 30 and 60 mg demonstrated significant
      pain improvement versus placebo, suggesting utility for some patients.

PMID- 21905972
TI  - Is smoking linked to positive symptoms in acutely ill psychiatric patients?
AB  - BACKGROUND: The self-medication hypothesis is commonly put forward to explain the
      high prevalence of smoking in psychiatric patients. However, studies supporting
      the self-medication hypothesis have most often been carried out on chronic
      patients stabilized by antipsychotics. AIM: Given that antipsychotics tend to
      erase psychiatric symptoms, the present study was undertaken on acutely ill
      patients usually receiving no medications, or on whom medications are
      ineffective. METHODS: Participants were 492 consecutively hospitalized patients.
      They were evaluated the day of their hospitalization with the Brief Psychiatric
      Rating Scale (BPRS, 18 items). Urinary cotinine and creatinine were measured the
      morning following their hospitalization. The urinary cotinine/creatinine ratio
      and the cotinine/creatinine/number of cigarettes smoked per day ratio (nicotine
      extraction index) were calculated for each patient. RESULTS: The positive
      symptoms subscale of the BPRS significantly correlated with smoking, whereas
      other BPRS subscales did not. In patients with mood disorder, the nicotine
      extraction index correlated with the positive symptoms, activation and hostility
      subscales, but not with the negative symptoms subscale. Analyses of individual
      BPRS items using the cotinine/creatinine ratio measure showed that smoking is
      positively associated with "unusual thought content" and "grandiosity" items and
      negatively associated with "guilt feeling", "depressed mood" and "motor
      retardation". Analyses of individual BPRS items using the nicotine extraction
      index showed a positive association only with "unusual thought content" and
      "grandiosity" items. Patients with schizophrenia extract more nicotine from
      cigarettes than other patients. CONCLUSION: In acutely ill psychiatric patients,
      smoking is linked with positive symptoms and not with negative symptoms.

PMID- 21905973
TI  - Parameters of mineral metabolism predict midterm clinical outcome in end-stage
      heart failure patients.
AB  - OBJECTIVES: We investigated to which extent disturbances in mineral metabolism
      predict 90-day clinical outcome in end-stage heart failure patients. DESIGN:
      Among numerous biochemical parameters, we measured serum levels of sodium and
      magnesium, the calciotropic hormones parathyroid hormone and 1,25
      dihydroxyvitamin D as well as fibroblast growth factor-23 (a phosphaturic
      hormone) in 305 cardiac transplant candidates. Primary endpoint was a composite
      of the need of mechanical circulatory support (MCS), transplantation, or death.
      RESULTS: Of the study cohort, 33.4% reached the primary endpoint. In detail, 19%
      were transplanted (the vast majority was listed "high urgent"), 8.8% died and
      5.6% received MCS implants. As determined by logistic regression analysis, all
      aforementioned biochemical parameters were independently related to the primary
      endpoint. Results did not change substantially when transplanted patients were
      censored. A risk score (0-5 points) was developed. Of the patients who scored 5
      points 89.5% reached the primary endpoint whereas of the patients with a zero
      score only 3.8% reached the primary endpoint. CONCLUSIONS: Our data demonstrate
      that in addition to the well-known predictive value of disturbed sodium
      metabolism, derangements in calcium, phosphate, and magnesium metabolism also
      predict midterm clinical outcome in end-stage heart failure patients.

PMID- 21905974
TI  - Diagnostic accuracies of MR enterography and CT enterography in symptomatic
      Crohn's disease.
AB  - OBJECTIVE: In patients, with symptomatic Crohn's disease (CD), valid information
      about the presence or absence of small bowel disease activity and stenosis is
      clinically important. Such information supports decisions about medical or
      surgical therapy and can be obtained with MR enterography (MRE) or CT
      enterography (CTE). MATERIALS AND METHODS: A total of 50 patients with
      symptomatic pre-existing CD and a demand for small bowel imaging to support
      changes in treatment strategy were included in this prospective and blinded
      study. MRE and CTE were performed on the same day in alternating order and
      subsequently compared with the gold standard: pre-defined lesions at ileoscopy (n
      = 30) or surgery with (n = 12) or without (n = 3) intra-operative enteroscopy.
      RESULTS: A total of 35 patients had active small bowel CD (jejunum 0, ileum 1,
      (neo)-terminal ileum 34) and 20 had small bowel stenosis. The sensitivity and
      specificity of MRE for detection of small bowel CD was 74% and 80% compared to
      83% and 70% with CTE (p >= 0.5). MRE and CTE detected small bowel stenosis with
      55% and 70% sensitivities, respectively (p = 0.3) and 92% specificities.
      CONCLUSIONS: MRE and CTE have comparable diagnostic accuracies for detection of
      small bowel CD and stenosis. In symptomatic patients with CD and high disease
      prevalence, positive predictive values are favorable but negative predictive
      values are low. Consequently, MRE and CTE can be relied upon, if a positive
      result is obtained whereas a negative enterography should be interpreted with
      caution.

PMID- 21905975
TI  - Clinical significance of colonoscopic examination in patients with early stage of
      gastric neoplasm undergoing endoscopic submucosal dissection.
AB  - OBJECTIVE: We aimed to determine the frequency of colorectal neoplasm in patients
      with early gastric neoplasm who underwent endoscopic submucosal dissection (ESD)
      compared to healthy controls and to investigate their risk factors for colorectal
      neoplasm. METHODS: A total of 107 patients with gastric neoplasm including 54
      gastric adenoma and 53 early gastric cancer (EGC) that underwent ESD and 107
      sex/age-matched healthy controls were enrolled. All of the subjects underwent
      colonoscopy for routine check-up. High-risk colorectal neoplasm were defined as
      >1 cm, three or more polyps, adenoma with villous component, adenoma with high
      grade dysplasia or adenocarcinoma. RESULTS: The frequency of overall colorectal
      neoplasm was 56.1% in the gastric neoplasm group and 34.6% in the control group
      (p < 0.005). High-risk colorectal neoplasm was found in 26.2% of patients with
      gastric neoplasm and 12.1% of controls (p < 0.01). In each gastric adenoma and
      EGC subgroups, the frequency of overall colorectal neoplasm was higher than each
      control subgroup. The frequency of high-risk colorectal neoplasm in EGC subgroup
      was significantly higher than that in the control subgroup, against not being in
      gastric adenoma subgroup. The risk factors for overall colorectal neoplasm were
      age and presence of gastric neoplasm, and that for high risk colorectal neoplasm
      was the only presence of gastric neoplasm. CONCLUSIONS: The frequency of overall
      and high-risk colorectal neoplasm in the gastric neoplasm group was higher than
      that in the control group. Therefore, a screening colonoscopy should be
      considered in patients with early gastric neoplasm undergoing ESD.

PMID- 21905976
TI  - YKL-40 and transient elastography, a powerful team to assess hepatic fibrosis.
AB  - OBJECTIVE: Transient elastography (TE) is a non-invasive and accurate method for
      the diagnosis of severe hepatic fibrosis and cirrhosis (F = 3 and F = 4).
      However, the assessment of significant fibrosis (F = 2) by TE is impaired due to
      a high variation in the diagnostic accuracy. Within this study, we aim to compare
      the diagnostic value of TE and experimental biomarkers of liver fibrosis.
      MATERIAL AND METHODS: A total of 55 patients with chronic liver disease of
      different etiologies were included in the study. Among them, patients with HCV
      infection represented the largest cohort (n = 25). Liver fibrosis was evaluated
      according to the Desmet/Scheuer score. All patients received TE. Serum
      concentrations of YKL-40, hyaluronic acid (HA), Laminin, C-terminal procollagen I
      peptide, MMP-9, TIMP-1, TIMP-2 and MMP-9/TIMP-1 complex were determined by ELISA.
      RESULTS: In the total patient population, areas under the receiver operator
      characteristic curve (AUROC) for TE were 0.798 (F >= 2), 0.880 (F >= 3) and 1 (F
      = 4). Among the serum markers, highest diagnostic accuracies were calculated for
      YKL-40 for F >= 2 (0.792) and F >= 3 (0.914) and for YKL-40 and HA for F = 4
      (both 0.936). In the subgroup of HCV patients, the following AUROCs for TE were
      calculated: 0.802 (F >= 2), 0.798 (F >= 3) and 0.998 (F = 4). YKL-40 exhibited
      the highest diagnostic accuracy of all biomarkers in the HCV population (0.880,
      0.854 and 0.986, respectively). CONCLUSIONS: YKL-40 is a powerful fibrosis marker
      with high diagnostic accuracy, in particular in HCV-associated liver disease. Its
      determination may confirm and improve the diagnostic accuracy of TE especially in
      early stages of liver fibrosis.

PMID- 21905977
TI  - IFN beta 1b induced celiac disease.

PMID- 21905978
TI  - C-reactive protein level as a predictor of mortality in liver disease patients
      with bacteremia.
AB  - BACKGROUND AND OBJECTIVE: C-reactive protein (CRP) is synthesized in the liver in
      response to inflammation, and CRP is a widely used marker of sepsis. In
      bacteremia the initial CRP level is an independent predictor of mortality. Since
      the CRP response in patients with chronic liver disease is lower than in patients
      without liver disease the objective was to assess whether CRP levels in chronic
      liver disease and bacteremia was associated with case fatality. PATIENTS: The
      study enrolled 105 patients with chronic liver disease and bacteremia as well as
      202 patients with bacteremia and no recorded liver disease from the same region
      and time period. METHODS: Retrospective review of medical records with
      registration of demography, co-morbidity, bacteriological, biochemical and
      clinical findings, and Child-Turcotte-Pugh scores. The primary outcome was 30-day
      mortality. RESULTS: Mortality was significantly higher in patients with chronic
      liver disease (mortality rate ratio 2.2; 95% confidence interval 1.2-3.9) and it
      was correlated to Child-Turcotte-Pugh scores. CRP levels were not different
      between the three Child-Turcotte-Pugh classes (p = 0.33), and no linear
      correlation with 30-day mortality was observed. CONCLUSION: Mortality associated
      with bacteremia is increased in patients with chronic liver disease and it is
      correlated with Child-Turcotte-Pugh score. The prognostic information of initial
      CRP levels in patients with chronic liver disease is weak. The clinical
      management of patients with chronic liver disease and suspected infection should
      initiate antimicrobial therapy based on clinical, radiological and
      microbiological findings, whereas the measurement of CRP in bacteremia is less
      helpful as compared with patients without liver disease.

PMID- 21905979
TI  - Limited value of fecal calprotectin in patients with liver cirrhosis.

PMID- 21905980
TI  - Screening for unrecognized coeliac disease in subfertile couples.
AB  - OBJECTIVE: Subfertility has been reported as a long-term complication of
      unrecognized and/or untreated coeliac disease (CD); however, the results from
      studies on this topic are ambiguous. We aimed to determine the prevalence of
      unrecognized CD in subfertile male-female couples visiting a fertility clinic
      compared with the general population. METHODS: Subjects included 1038 male-female
      couples (n = 2076) who visited the fertility clinic of the Leiden University
      Medical Center in the Netherlands between 2003 and 2009. All consecutive patients
      were routinely, serologically screened, and those with positive test results for
      antibodies against IgA anti-tissue transglutaminase type 2 and IgA endomysial
      antibodies were considered to have unrecognized CD. Clinical data on gender, age,
      height, weight, diagnosis of subfertility, and previously diagnosed CD were
      collected from the clinical files. Subsequently, after serological screening, all
      patients were anonymized. The prevalence of unrecognized CD was compared with the
      one in the general adult population in the Netherlands (0.35%). RESULTS: The
      prevalence of unrecognized CD in subfertile male-female couples was 0.48%
      (10/2076; 6 females and 4 males) and was not significantly more frequent compared
      with the general population. Compared with the control group, similar CD
      prevalences were found within the different subfertility categories separately:
      unexplained subfertility, anovulation, tubal pathology, and male factor (p = NS).
      CONCLUSION: In our large study cohort of subfertile male-female couples, the
      prevalence of unrecognized CD is comparable to the general population in the
      Netherlands. No association was observed between CD and subfertility in the
      different subfertility categories and genders.

PMID- 21905981
TI  - A decision support model for cost-effectiveness of radical prostatectomy in
      localized prostate cancer.
AB  - OBJECTIVE: This study aimed to develop a probabilistic decision support model to
      calculate the lifetime incremental cost-effectiveness ratio (ICER) between
      radical prostatectomy and watchful waiting for different patient groups. MATERIAL
      AND METHODS: A randomized trial (SPCG-4) provided most data for this study. Data
      on survival, costs and quality of life were inputs in a decision analysis, and a
      decision support model was developed. The model can generate cost-effectiveness
      information on subgroups of patients with different characteristics. RESULTS: Age
      was the most important independent factor explaining cost-effectiveness. The cost
      effectiveness value varied from 21,026 Swedish kronor (SEK) to 858,703 SEK for
      those aged 65 to 75 years, depending on Gleason scores and prostate-specific
      antigen (PSA) values. Information from the decision support model can support
      decision makers in judging whether or not radical prostatectomy (RP) should be
      used to treat a specific patient group. CONCLUSIONS: The cost-effectiveness ratio
      for RP varies with age, Gleason scores, and PSA values. Assuming a threshold
      value of 200,000 SEK per quality-adjusted life-year (QALY) gained, for patients
      aged <=70 years the treatment was always cost-effective, except at age 70,
      Gleason 0-4 and PSA <=10. Using the same threshold value at age 75, Gleason 7-9
      (regardless of PSA) and Gleason 5-6 (with PSA >20) were cost-effective. Hence, RP
      was not perceived to be cost-effective in men aged 75 years with low Gleason and
      low PSA. Higher threshold values for patients with clinically localized prostate
      cancer could be discussed.

PMID- 21905982
TI  - Caries prevalence in Danish pre-school children delivered vaginally and by
      caesarean section.
AB  - OBJECTIVE: The mode of delivery may significantly influence the diversity and
      composition of the oral microflora and facilitate early acquisition of mutans
      streptococci. The aim was to compare caries prevalence and experience in 3-year
      old children delivered vaginally and by caesarean section (C-section). MATERIALS
      AND METHODS: The study had an observational cohort protocol based on extracted
      information from governmental databases and nationwide registers concerning
      birth, social and educational levels and dental status. Children born at the
      Copenhagen University Hospital in 2005 were eligible and the final study group
      with complete information consisted of 594 children, 443 delivered vaginally and
      151 by C-section. RESULTS: The total caries prevalence was 8% and no significant
      difference was displayed between the groups. When only the children with caries
      (dmfs > 0) were compared, those delivered by C-section had a higher mean value in
      comparison with those delivered vaginally (dmfs 6.8 vs 3.2), but the difference
      was not statistically significant. There was a significant relationship between
      caries prevalence and low family income in the total study group (OR = 5.8, p <
      0.05). CONCLUSIONS: Within the limitations of this observational cohort study,
      caries prevalence in 3-year-old children was not related to the mode of delivery.
      However, the tendency of more severe caries in the C-section group justifies
      further studies, preferably with a prospective design.

PMID- 21905983
TI  - Well-being and occupational rights: an imperative for critical occupational
      therapy.
AB  - BACKGROUND: One of occupational therapy's core assumptions is that engagement in
      occupations influences well-being. Because occupational engagement is integral to
      human well-being, and because well-being is integral to human rights, this paper
      contends that the ability and opportunity to engage in occupations is an issue
      that concerns rights. AIMS: To outline well-being and its centrality to human
      rights; to explore the relationships between well-being and occupation and
      between well-being and occupational rights; and to highlight the consequent
      imperative to engage in critical occupational therapy. KEY ISSUES: The World
      Federation of Occupational Therapists asserts that all people have the right to
      participate in a range of occupations that enable them to flourish, fulfil their
      potential, and experience satisfaction congruent with their culture and beliefs;
      and further asserts the human right to equitable access to participation in
      occupation. CONCLUSIONS: If occupational therapists are to take seriously their
      espoused commitment to enabling equitable access to participation in occupation,
      the inequitable conditions of people's lives will need to be addressed. Critical
      occupational therapy is a committed form of practice which acknowledges that well
      being cannot be achieved solely by enhancing individuals' abilities, and that
      consequently endeavours also to address the conditions of people's lives.

PMID- 21905984
TI  - The Assessment of Awareness of Ability (A3) in a Japanese context: a Rasch model
      application.
AB  - The overall aim of this study was to evaluate the validity of the Assessment of
      Awareness of Ability (A3) in a Japanese context. The A3 (formerly known as the
      Assessment of Awareness of Disability, AAD) is a standardized 11-question
      interview used to explore the discrepancy between observed strengths and
      limitations in the performance of activities of daily living (ADL) according to
      the Assessment of Motor and Process Skills (AMPS) and the limitations described
      by the client. In this study, 259 matched Swedish and Japanese A3 data records
      were analyzed using a Rasch partial credit model (PCM). The analysis of rater
      consistency and items demonstrated acceptable goodness-of-fit according to the
      PCM, indicating rater consistency and internal scale validity. The A3 can help
      clients and therapists understand discrepancies between observed and self
      reported performance aspects of various everyday tasks within Japanese and
      Swedish contexts.

PMID- 21905985
TI  - Maternal docosahexaenoic acid feeding protects against impairment of learning and
      memory and oxidative stress in prenatally stressed rats: possible role of
      neuronal mitochondria metabolism.
AB  - AIMS: Docosahexaenoic acid (22:6n-3; DHA) is known to play a critical role in
      postnatal brain development. However, no study has been performed to investigate
      its preventive effect on prenatal stress-induced behavioral and molecular
      alterations in offspring. In the present study, rats were exposed to restraint
      stress on days 14-20 of pregnancy, three times a day, 2 hours each time; DHA was
      given at the doses of 100 and 300 mg/kg/day for two weeks. RESULTS: We showed
      that prenatal restraint stress caused (1) learning and memory impairment, (2)
      BDNF mRNA level decrease, (3) oxidative damage to proteins, (4) enhanced
      expression of nitric oxide synthase and apoptosis, and (5) abnormalities in
      mitochondrial metabolism that included changes in mitochondrial complexes I-V,
      and enhancement of expression of proteins involved in mitochondrial
      fusion/fission (Mfn-1, Mfn-2, Drp-1) and autophagy (Atg3, Atg7, Beclin-1, p-Akt,
      and p-mTOR) in the hippocampus of offspring. INNOVATION: Besides the well-known
      role in child brain development, we reported the novel finding of DHA in
      protecting prenatal stress-induced cognitive dysfunction involving the modulation
      of mitochondrial function and dynamics. CONCLUSION: Maternal feeding of DHA
      significantly prevented prenatal stress-induced impairment of learning and memory
      and normalized the biomarkers of oxidative damage, apoptosis, and mitochondrial
      metabolism in the hippocampus of both male and female offspring. These results
      suggest that maternal feeding of DHA exerts preventive effects on prenatal stress
      induced brain dysfunction and that modulation of mitochondrial metabolism may
      play critical role in DHA protection.

PMID- 21905986
TI  - Conceptualising molecular psychiatry and translational psychiatry.
AB  - The terms "molecular psychiatry" and "translational psychiatry" are frequently
      used key words of today's scientific community. However, the exact meaning of
      these terms remains surprisingly unclear. They also seem to be interpreted in
      different ways by different authors. Here, we first analyse how the terms have
      emerged historically and then try to indicate how meaningful and widely
      acceptable definitions could be achieved. Clearly, with the further development
      of these emerging psychiatric research areas, it will be necessary to regularly
      adjust these definitions accordingly.

PMID- 21905987
TI  - Modern neuroimaging in psychiatry: towards the integration of functional and
      molecular information.
AB  - Thirty-five years of psychiatric imaging along traditional diagnostic boundaries
      have revealed a great deal about the structural and functional brain changes that
      accompany mental disorders but not produced reliable biomarkers. One reason may
      be that clinical syndromes represent the phenotypic expression of many different
      genotypes and biological pathways. Neuroimaging is now increasingly being used to
      map out the pathways from genes (obtained from candidate or genome-wide
      association studies) to the cognitive, emotional and behavioural phenotypes that
      result in syndromes like schizophrenia or depression. The armamentarium of
      neuroimaging is becoming increasingly versatile, and now includes methods with
      considerable spatial, temporal and/or molecular resolution. We can expect that a
      sophisticated combination of these techniques with genetic and pharmacological
      information will usher into a new era of psychiatric imaging that will aid a
      biological classification of mental diseases.

PMID- 21905988
TI  - Pharmacotherapy in depressed children and adolescents.
AB  - In children and adolescents, antidepressants are used in the treatment of
      depressive symptoms and several other psychiatric conditions. In the treatment of
      mild and moderate depressive symptoms, non-pharmacological approaches such as
      psychotherapy play a major role, a severe symptomatology may demand a combination
      with antidepressants. As first-choice medication for the treatment of juvenile
      depression, the selective serotonin reuptake inhibitor (SSRI) fluoxetine is
      recommended, due to its efficacy and approval. As second-choice antidepressants
      the SSRIs sertraline, escitalopram and citalopram might be used. Other
      antidepressants - such as tricyclic antidepressants, alpha(2)-adrenoceptor
      antagonists, selective noradrenalin reuptake inhibitors (SNRI) - may be
      alternatively used, but not as first- or second-choice medications. In the case
      of "off-label" use, patients and parents have to be carefully informed prior to
      the start of medication, after a thorough risk-benefit analysis. In the following
      overview we address a general framework, therapeutic strategies and the issues of
      antidepressant pharmacotherapy for the treatment of unipolar depression in
      childhood and adolescence.

PMID- 21905989
TI  - Gene therapy for psychiatric disorders.
AB  - There is no indication that gene therapy can be applied in psychiatric patients
      any time soon. However, there are several promising developments on the level of
      experimental neuroscience indicating that gene therapy approaches have an effect
      in animal models of several psychiatric disorders including drug addiction,
      affective disorders, psychoses and dementia, modifying behavioural parameters via
      interventions on the molecular and cellular level. However, before gene therapy
      in psychiatric disorders can be considered on the human level, not only
      neurobiological and technical problems need to be overcome, but also important
      ethical questions answered.

PMID- 21905990
TI  - Discovering a new anatomical structure in the brain: implications for
      neuropsychiatry and therapy.
AB  - Describing new brain structures may open research avenues and improve our
      knowledge of brain functions and of brain disorders. It may also provide new
      neuroanatomical targets for treatments. A detailed understanding of neuroanatomy
      is a prerequisite of understanding the pathomechanisms underlying psychiatric
      disorders on a molecular and cellular level. The tail of the ventral tegmental
      area (tVTA), also known as rostromedial tegmental nucleus (RMTg), is a recently
      described region which may be a major inhibitory control centre for the
      dopaminergic systems. These systems participates to behavioural functions and are
      implicated in the aetiology, symptoms or treatment of neurological or psychiatric
      diseases, such as Parkinson's, schizophrenia, mood disorders, attention-deficit
      hyperactivity-disorder (ADHD) and drug abuse. Belonging to the reticular
      formation, the tVTA may constitute a major inhibitory GABAergic input to these
      dopaminergic systems. Moreover, it is sensitive to drugs of abuse, to stimulant
      or arousing drugs, to aversive stimuli and it could also be the main relay
      between lateral habenula and VTA. First described in rats, and proposed as a
      component of the emotional motor system implicated in basic survival behaviours,
      tVTA appears as a relevant structure for molecular psychiatry, which should
      foster research to define and study this brain region in the human brain.

PMID- 21905991
TI  - Forensic patients with organic brain disorders.
AB  - Present literature states that people with acquired organic brain dysfunctions
      face problems with attention, executive functions and social interaction. During
      the past years an increasing number of patients with organic brain disorders have
      been committed into our forensic psychiatry. In current literature studies on
      this group of patients are underrepresented. This study wanted to verify the
      impairment of cognitive functions of this specific group of patients. Included
      were all patients of the forensic psychiatry in Rostock (Mecklenburg-Western
      Pomerania) with a primary or secondary organic brain dysfunction who have been
      committed into the clinic since 2009. These patients went through an extensive
      neuropsychological test battery. It was found that patients affected by organic
      brain dysfunction achieve lower results in the neuropsychological testing than
      non impaired patients, but their results are not as below average than it would
      have been expected. Further studies should show, if these patients are able to
      improve their performance while successfully undergoing psychotherapy.

PMID- 21905992
TI  - Translational research approach to biological and modifiable risk factors of
      psychosis and affective disorders.
AB  - OBJECTIVES: This review summarizes the literature on (molecular-) biological,
      medical, environmental and modifiable risk factors for psychosis and mood
      disorders with the view of their suitability for translational research and
      mental health practice from preventative and clinical treatment perspectives.
      METHODS: This review summarized literature on biological, medical, environmental
      and modifiable risk factors for psychosis and mood disorders evaluating their
      potential for translational research and clinical practice. RESULTS: Based on the
      concept of the gene - environment interaction in the development of mental
      disorders, we highlight the numerous risk factors reported to contribute to an
      increased susceptibility to schizophrenia and mood disorders of young adults to
      late-life. Special emphasis is placed onto the discussion on the requirement of
      translational and interdisciplinary research approaches integrating basic and
      clinical neuroscience approaches that may have important implications for future
      studies and clinical practice. CONCLUSIONS: Interdisciplinary research approaches
      integrating developmental neuroscience and policy makers are encouraged in order
      to achieve effective prevention and intervention programs addressing
      environmental, behavioural, biological factors relevant to psychiatric disorders
      during young ages, adulthood and aging.

PMID- 21905993
TI  - Intelligence moderates impulsivity and attention in ADHD children: an ERP study
      using a go/nogo paradigm.
AB  - OBJECTIVES: If the cardinal symptoms of ADHD - hyperactivity, impulsivity and
      inattention - are combined with a learning disability (70 >= IQ < 85), the
      question arises whether a child shows hyperkinetic behaviour because of
      intellectual overload in a challenging situation, for example at school. Perhaps,
      this behaviour is not a primary attention deficit disorder but an impulse control
      disorder, determined by the primarily intelligence level. It raised the question
      whether attention deficit and impulse control regarded as behavioural inhibition
      deficit may depend on intelligence and therefore should be separated into
      distinct clinical entities. METHODS: A total of 45 children (15 with ADHD, 15
      with learning disabilities (LD), 15 with ADHD and learning disabilities) were
      compared in a matched-pair design with 42 control children using a go/no go
      paradigm (visual continuous performance test, CPT). The dependent variable was
      the target P3 amplitude, averaged from a 10-20 EEG measurements under distinct
      trigger conditions. For statistical analysis, a three-factor analysis of variance
      (MANOVA) with repeated measurements was used. In a subsequent regression analysis
      with residuals, the influence of intelligence (IQ) was calculated and a "parallel
      analysis of variance" was conducted. RESULTS: No differences in the P3 amplitudes
      in the comparison ADHD-control group were found. Reduced P3 amplitudes as main
      effects in the LD group compared with controls were found and a significant group
      dependent interaction on reduced P3 amplitudes comparing ADHD + LD versus control
      group. Using residuals (IQ), this interaction was not longer verifiable.
      CONCLUSION: Impulsivity and attention deficit as the cardinal symptoms of ADHD,
      regarded as behavioural inhibition deficit, are essentially moderated by the
      primary intelligence, rather than by an attention deficit. The lower the IQ, the
      more ADHD surfaces as a disturbed impulsivity and lesser as an attention deficit.

PMID- 21905994
TI  - Chronotherapeutics and psychiatry: setting the clock to relieve the symptoms.
AB  - Circadian rhythms are near 24-h cycles in a number of physiological and
      behavioural parameters and the underpinning circadian timing systems is one of
      the key homeostatic regulatory systems in mammalian physiology. Many common
      psychiatric conditions are associated with disrupted sleep, including a common
      occurrence of delayed or advanced phase sleep syndromes, which in themselves may
      be indicative of dysregulated circadian timing in these disorders. In this
      article we discuss the evidence for abnormal circadian rhythms in seasonal
      affective disorder, bipolar disorder and attention deficit/hyperactivity
      disorder. Much of this evidence suggest that these conditions are associated with
      either phase delays or phase advances of core phase markers of the circadian
      clock such as melatonin or core body temperature, suggesting the presence of
      circadian desynchrony in these conditions. We also highlight findings that
      pharmacological and/or behavioural interventions that ameliorate circadian
      misalignments are efficacious in producing symptomatic relief, suggesting an
      intrinsic link between the circadian and affective systems that can be
      manipulated for clinical benefit.

PMID- 21905995
TI  - Characterisation of different nanoparticles with a potential use for drug
      delivery in neuropsychiatric disorders.
AB  - OBJECTIVES: Nanoparticles are promising tools for targeted delivery of drugs in
      the treatment of different diseases, including neuropsychiatric disorders.
      However, they need to be carefully characterised for any adverse effects which
      may occur in their presence. In this study, we evaluated the applicability of
      nanoparticles that belong to three different groups: (i) aggregates from
      amphiphilic diblock copolymers composed of poly(2-ethyl-2-oxazoline) (PEtOx) and
      poly(2-phenyl-2-oxazoline) (PPhOx) in different ratios, (ii) stabilised polymeric
      micelles (SPM) based on poly(ethylene oxide)-b-poly(propylene oxide)
      bpoly(ethylene oxide) (PEO-PPO-PEO) and (iii) star-like polymer with poly(acrylic
      acid) arms and branched polystyrene interior (PSPAA). METHODS: Using cultured
      human neural progenitor cells, we characterised six nanoparticles (POx-9, POx-23
      and POx-46 - the polyoxazoline group, SPM-F38 and SPMMS - the SPM group, and
      PSPAA - the star-like polymer) for neurotoxicity and effect on neurodevelopmental
      genes. Nanoparticles ability to activate complement system in blood was assessed
      by ELISA. RESULTS: None of the nanoparticles exhibited neurotoxicity. However,
      POx-9, POx-23, POx-46 and SPM-F38 activated complement system. POx-9 and SPM-F38
      resulted in inhibition of expression of 19 and 26 out of 30 tested
      neurodevelopmental genes, respectively. CONCLUSIONS: Considering the properties
      of the studied nanoparticles, only PSPAA and SPMMS can be used at high
      concentrations for drug delivery without compromising neurogenesis and
      neurodevelopment, and activation of complement system.

PMID- 21905996
TI  - Comorbidity of schizophrenia and adult attention-deficit hyperactivity disorder.
AB  - OBJECTIVES: Adult ADHD is characterised by a plethora of comorbid conditions.
      However, the comorbidity of schizophrenia and ADHD does not seem to be a typical
      feature and is therefore under-researched. OBJECTIVE: To identify adult patients
      with schizophrenia and comorbid ADHD and compare their symptomatology with
      schizophrenic patients without ADHD. METHOD: Performance in specific
      neuropsychological tests (set shifting, selective and sustained attention,
      cognitive performance, and speed of information processing) was determined.
      Additionally, important demographic data and information about the patients'
      history such as the number of suicide attempts were gathered. Twenty-seven
      patients were involved in this study (14 male and 13 female). Fifteen patients
      were diagnosed with schizophrenia/no ADHD and twelve had both schizophrenia/ADHD.
      RESULTS: We report here an increase in suicidal behaviour of patients with both
      schizophrenia and ADHD compared to schizophrenia only. A significant
      underperformance of the patients with ADHD comorbidity compared to patients with
      schizophrenia only was also determined. CONCLUSIONS: The increased suicidal
      behaviour in patients with schizophrenia and ADHD suggests the need of further
      studies on mood regulation and suicidal ideations in these patients.

PMID- 21905997
TI  - Repetitive transcranial magnetic stimulation (rTMS) for treatment of alcohol
      dependence.
AB  - OBJECTIVES: Neuroimaging studies have found that alcohol dependent patients
      display dopaminergic dysfunction in the ventral striatum, which is associated
      with alcohol craving. Repetitive transcranial magnetic stimulation (rTMS) was
      introduced as a promising new treatment option for depression, and among other
      neurobiological mechanisms, it is able to stimulate the striatal dopaminergic
      system. The aim of our study was to investigate the effect of high frequency rTMS
      of the left dorsolateral prefrontal cortex compared to sham stimulation on
      craving and mood in alcohol dependent women. Furthermore, the impact on an
      attentional blink (AB) paradigm to pictures with neutral, emotional and alcohol
      related contents was proofed. METHODS: Nineteen female detoxified patients were
      randomized either to a high frequency rTMS (20 Hz) over the left DLPFC (n = 10)
      or a sham stimulations (n = 9) at 10 days. Alcohol craving was determined with
      the Obsessive Compulsive Drinking Scale, depressive symptoms were registered by
      means of Hamilton Depression Rating Scale and Beck' Depression Inventory. For the
      AB paradigm an age-matched control group was investigated. RESULTS: There were no
      significantly differences between both groups regarding alcohol craving or mood.
      In the AB paradigm, real stimulated patients detected alcohol related T2 targets
      incorrectly in comparison to the sham stimulated and control subjects. SUMMARY:
      Although there were no differences in clinical parameters such as craving or mood
      after real high frequency rTMS compared to sham stimulation, we found an
      interesting difference between the real and the sham stimulated group and
      controls in the AB paradigm indicating an increase of the AB effect to alcohol
      related pictures after real stimulation. Further studies are needed to replicate
      these findings and correlate them to clinical and neurophysiological data.

PMID- 21905998
TI  - Transforming poison into medicine: the role of dualism in psychiatry.
AB  - This article draws attention to a generalizable phenomenon called "transforming
      poison into medicine," illustrating both literal and figurative applications. The
      purpose of such illustrations is to support a strong philosophical claim, namely
      the currently incomplete reduction (if not the ultimate irreducibility) of
      intentional mind-states - e.g., beliefs, desires, volitions - to electro-chemical
      brain-states. Such incomplete reduction (or irreducibility) holds profound
      implications for the ineluctable role of dualism in neuroscience and psychiatry
      alike.

PMID- 21905999
TI  - Enhanced emotional interference on working memory performance in adults with
      ADHD.
AB  - OBJECTIVES: Subjects with attention-deficit/hyperactivity disorder (ADHD) suffer
      from both executive dysfunction and deficits in emotion regulation. However, up
      to now, there has been no research demonstrating a clear impact of emotional
      dysregulation on cognitive performance in subjects with ADHD. METHODS: Male and
      female adults with ADHD (n=39) and gender- and IQ-matched control subjects (n=40)
      performed an emotional working memory task (n-back task). In the background of
      the task, we presented neutral and negative stimuli varied in emotional saliency
      (negative pictures with low saliency, negative pictures with high saliency), but
      subjects were instructed to ignore these pictures and to process the working
      memory task as quickly and as accurately as possible. RESULTS: Compared to
      control subjects, ADHD patients showed both a general working memory deficit and
      enhanced distractability by emotionally salient stimuli in terms of lower n-back
      performance accuracy. In particular, while controls showed impaired WM
      performance when presented with highly arousing negative background pictures, a
      comparable decrement was observed in the ADHD group already with lowly arousing
      pictures. CONCLUSIONS: Our results suggest that difficulties in suppressing
      attention towards emotionally laden stimuli might result from deficient executive
      control in ADHD.

PMID- 21906000
TI  - A new approach in psychotherapy: ACT (acceptance and commitment therapy).
AB  - Acceptance and commitment therapy (ACT) focuses on enhancing psychological
      flexibility in the service of achieving core life values. One thing that
      distinguishes ACT from other psychotherapies is its grounding in empirical
      behavioural science. The results of the latter suggest that the capacity for
      human language can produce seriously negative psychological effects under certain
      circumstances. ACT is a therapeutic approach in which the negative effects of
      human language are undermined so as to support flexible values based living. ACT
      therapeutic work involves six key processes proposed under the "hexaflex" model.
      ACT has received considerable empirical support at a number of different levels
      of analysis.

PMID- 21906001
TI  - Pilot study of the application of magnetic bead protein profiling to the study of
      biomarkers in addiction research.
AB  - OBJECTIVES: Proteomic technologies based on mass spectrometry are increasingly
      used as a valuable tool in clinical research allowing high-throughput protein and
      peptide profiling to be undertaken. Whilst previous research has focussed the
      application of this novel technology on the study of patients with disorders
      compared to comparable individuals from the healthy population, this current
      study seeks to determine the effect of successful treatment for alcoholism on the
      serum protein profile obtained. METHODS: Serum samples were collected from
      patients after initial treatment for alcohol abuse and also 6 months after
      treatment. The serum samples were prepared for analysis using reverse phase
      magnetic bead fractionation and the resulting peptides analysed by matrix
      assisted laser desorption ionisation time-of-flight (MALDI-ToF) mass
      spectrometry. RESULTS: Whilst the majority of the peptides detected by this
      approach exhibited constant levels between the two time points, three peptides
      were elevated at the 6-month time point compared to the initial sampling.
      CONCLUSIONS: Whilst disorders with very clear biological causes (such as cancer)
      exhibit significantly different peptide profiles, psychiatric disorders such as
      alcohol addiction which are multifactorial show less obvious changes. Despite
      this the two groups of samples could statistically be distinguished by certain
      peptides expression levels.

PMID- 21906002
TI  - Diagnostic characteristics of inpatients in a Western African psychiatric
      hospital.
AB  - Little is known about psychiatric patients and psychiatric service delivery in
      non-Western developing countries. Therefore, this naturalistic pilot study aimed
      at analysing and describing the patient population treated in the Tanka Tanka
      Psychiatric Hospital, the mental health inpatient facility of The Gambia. Most
      patients were male and exhibited a wide age range of over 40 years. There were
      also indicators that the hospital population consisted of two distinguished
      groups: a large group of chronically ill patients and a smaller group of
      psychiatric patients with very acute symptoms. Psychotic/mood disorders and
      substance dependence/abuse were the most common diagnoses. In many patients
      problematic cannabis use was prevalent. Such research can contribute to better
      understand the needs of psychiatric patients, and help to develop continuously
      improved service delivery and optimise therapeutic options.

PMID- 21906003
TI  - Pharmacological treatment of adult ADHD in Europe.
AB  - OBJECTIVES: It is now widely accepted that ADHD is a frequent chronic condition
      with a lifelong perspective. Adult ADHD is a reliable and valid diagnosis. The
      disorder and the co-morbid conditions can place a severe burden on the patients,
      their families and their partners, requiring adequate treatment. METHODS: A
      systematic literature search was conducted to review the available
      pharmacological treatment options for adults with ADHD in European countries.
      RESULTS: Supported by meta-analyses, stimulant medication is the first-line
      pharmacological therapy for adult ADHD. However, from a European perspective the
      pharmacological treatment options are very limited and only a minority of adults
      with ADHD in European countries receives adequate treatment. CONCLUSIONS: With
      reference to the epidemiological data, it seems very likely that the number of
      people with ADHD in Europe seeking multimodal treatment including
      pharmacotherapy, psychotherapy, coaching or other therapeutic services will
      increase profoundly during the coming years.

PMID- 21906004
TI  - Molecular pathophysiology of neurodegenerative disease caused by gammaPKC
      mutations.
AB  - OBJECTIVE: Spinocerebellar ataxia type 14 (SCA14) is an autosomal dominant
      neurodegenerative disorder, which is caused by missense mutations of PRKCG gene
      encoding gamma type protein kinase C (gammaPKC). To elucidate the pathophysiology
      of SCA14, we have analyzed the character of mutant gammaPKC causing SCA14,
      expressed in cultured cells. RESULTS: We found that most of mutant gammaPKCs were
      susceptible to cytoplasmic aggregation, suggesting that this aggregate-prone is
      involved in the etiology of SCA14. When expressed in cultured Purkinje cells,
      mutant gammaPKC inhibited the development of dendrites in a manner independent of
      its aggregate-prone, suggesting that other mechanism is implicated in the
      pathogenesis of SCA14. FRAP (fluorescence recovery after photobleaching) analysis
      demonstrated that mobility of mutant gammaPKC was slower than that of wild type
      in Purkinje cells. Furthermore, translocation of mutant PKC was attenuated when
      the cells was treated with high potassium solution. These results suggest that
      mutant gammaPKC forms oligomers in Purkinje cells. In addition, enzymological
      studies revealed that most of mutant gammaPKC had higher basal activity than wild
      one. However, the imaging analysis of gammaPKC demonstrated that mutations slowed
      the translocation of gammaPKC, which may explain the low accessibility of mutant
      gammaPKC to the plasma membrane. CONCLUSION: We propose that variety of mutant
      gammaPKC characters integrally and complicatedly participate in the
      pathophysiology of SCA 14.

PMID- 21906005
TI  - Reduction of gyrification index in the cerebellar vermis in schizophrenia: a post
      mortem study.
AB  - OBJECTIVES: In schizophrenia, alterations of the gyrification index (GI) have
      been measured in cortical brain regions and are related to neurodevelopmental
      disturbances. Cerebellar regions have been implicated in the pathophysiology of
      schizophrenia; however, the GI has not been investigated here so far. METHODS:
      Hence, in a post-mortem study we investigated the GI separately from the vermis,
      left and right hemisphere of the medial posterior cerebellum in nine
      schizophrenia patients and 10 healthy controls. GI was defined as length of the
      inner contour inclusively depth of the sulci divided by length of the outer
      contour of the cerebellar surface and measured by tracing contours on images
      obtained by a stereological workstation. RESULTS: In the vermis, GI was reduced
      in schizophrenia patients according to the methods of Zilles (P = 0.020) and
      Vogeley (P = 0.015). In the hemispheres, no differences have been observed. GI
      obtained by the two methods showed a high correlation (P < 0.001). Correlation
      analysis showed no influence of gender, postmortem interval and age. CONCLUSIONS:
      Decreased GI in the vermis of schizophrenia patients may result from
      neurodevelopmental disturbances, since folding of the brain occurs mainly during
      the perinatal period. MRI studies using automated GI processing in larger samples
      are needed to confirm our results.

PMID- 21906006
TI  - Altered mRNA expression of monoaminergic candidate genes in the blood of children
      with attention deficit hyperactivity disorder and autism spectrum disorder.
AB  - OBJECTIVES: In absence of objective clinical characteristics the identification
      of peripheral biomarkers in neuropsychiatric disorders is highly relevant for the
      diagnostic process and an individualized therapy. We analyzed mRNA-expression of
      monoaminergic candidate genes (DRD4, DRD5, TPH1) in peripheral tissue of patients
      with attention deficit hyperactivity disorder (ADHD) and autism spectrum
      disorders (ASD), highly comorbid with ADHD, searching for possible molecular
      markers for these disorders. METHODS: mRNA was obtained from children and
      adolescents with ADHD (n = 51) and ASD (n = 26), diagnosed according to ICD-10
      criteria, as well as healthy controls (n = 39). mRNA expression was determined
      via quantitative realtime PCR (qRT-PCR) from whole blood cells. RESULTS: The
      concentrations of DRD4-mRNA in the whole blood were significantly lower in ADHD
      and ASD children (19 of 26 comorbid with ADHD) compared to healthy controls. ASD
      patients revealed a significantly decreased DRD5 mRNA expression in comparison to
      the two other groups. CONCLUSIONS: Alterations in mRNA expression patterns
      provide further evidence for a relevant effect of the respective candidate genes
      in the pathophysiology of ADHD. Given their potential as biomarkers mRNA
      expression patterns may be useful tools in (differential-) diagnostic procedures
      of ADHD and ASD. Future studies may determine the sensitivity and specificity of
      these putative biomarkers in larger samples including further neuropsychiatric
      diagnoses.

PMID- 21906008
TI  - Availability of psychiatric medication in an urban area of The Gambia/West
      Africa.
AB  - The use of a wide and differentiated arsenal of psychopharmacological substances
      is integral part of modern psychiatric treatment in addition to non
      pharmacological interventions (e.g., psychotherapy). However, worldwide the
      access to such medication can vary considerably. In this study, access to a wide
      range of psychiatric medication including antidepressants, antipsychotics,
      tranquilisers, mood stabilisers and ADHD medication was analysed for the Western
      African country of The Gambia by surveying private pharmacies within the urban
      and sub-urban areas of Banjul, the country's capital. The results show that most
      of these pharmacies tend to keep a very limited range of psychiatric drugs in
      stock. In many instances only a tricyclic antidepressant (e.g., amitriptyline),
      the neuroleptic haloperidol and the benzodiazepine diazepam were readily
      available. None of the pharmacies kept ADHD medication in stock, and only very
      few had mood stabilisers. However, several pharmacies reported to be able to
      obtain at request most of the drugs from international sources, including
      atypical antipsychotics, SSRIs, and dual-acting antidepressants. Therefore, it
      can be concluded that in rapidly growing urban centres of developing countries
      exemplified by Banjul, the infrastructure for modern psychopharmacotherapy is
      well established, and that the lack of immediate access to modern
      psychopharmacological compounds represents not so much a genuine lack of
      availability, but rather a lack of demand which may be associated with the
      considerable cost-implications of such treatment and the absence of prescribers
      (i.e. psychiatrists and other doctors with an expertise in modern
      psychopharmacotherapy). To our knowledge this is the first such study for The
      Gambia and results might be representative for the wider Western African region.
      It also exemplifies the challenges psychiatry is facing in developing countries
      worldwide. It is essential that government-sponsored so-called "essential
      medication lists" are continuously updated in order to reflect the progress in
      medical research including psychopharmacology. Further research into how to
      facilitate psychopharmacotherapy is urgently needed in order to further improve
      psychiatric services.

PMID- 21906007
TI  - Atrophy outcomes in multicentre clinical trials on Alzheimer's disease: effect of
      different processing and analysis approaches on sample sizes.
AB  - Structural MRI markers may serve as surrogate endpoints in clinical trials on
      disease modification in Alzheimer's disease (AD). Here, we used a longitudinal
      MRI data set of total brain and cortical grey matter volumes from 66 patients
      with AD recruited across seven centres of the German Dementia Competence Network.
      We compared effect size estimates for the detection of a 25% reduction of atrophy
      progression between a priori segmentation of brain tissue, implementing an
      anatomical model of brain tissue distribution, and a posteriori segmentation that
      was not informed by an anatomical model. Additionally, we compared effect size
      estimates between fixed effects analysis and a mixed effects model, implementing
      a random effects term to account for variable spacing of observation times. A
      priori segmentation reduced the required sample size by 50%. Introducing a random
      effects term for time led to an additional 50% reduction of required samples
      sizes compared to fixed effects analysis. In summary, using a priori segmentation
      with mixed effects analysis reduced the sample size to detect clinically relevant
      treatment effects more than fourfold. The implementation of mixed effects models
      will enhance the power to detect treatment effects also with other classes of
      biological endpoints including molecular biomarkers of disease.

PMID- 21906009
TI  - Differential patterns of disordered eating in subjects with ADHD and overweight.
AB  - OBJECTIVES: Despite growing evidence for an association between overweight and
      attention-deficit/hyperactivity disorder (ADHD), still little is known about the
      mechanisms underlying this relationship. METHODS: Within a two (no ADHD, ADHD) *
      two (normal weight, overweight) factorial design (n = 94) we tested disordered
      eating behaviour in a laboratory breakfast procedure as well as delay aversion
      (DA) in male children aged 7-15 years. RESULTS: While children with ADHD tended
      to eat above the normal level particularly at the beginning of the meal, children
      with overweight tended to eat above the normal level throughout the whole meal.
      Furthermore, preference for immediately available food was predicted by parental
      ratings of inattention and neuropsychological measures of DA in overweight
      children, and by impulsivity in children with ADHD. CONCLUSIONS: Our results
      suggest distinct neuropsychopathological pathways to abnormal eating in ADHD and
      overweight. Thus, children with overweight might benefit more from specialized
      treatment programmes that aim at improving attention functions while in children
      with ADHD the treatment should focus on impulsivity.

PMID- 21906010
TI  - ADHD and offenders.
AB  - OBJECTIVES: To present the needs and psychological treatment options for
      offenders with ADHD. METHODS: Key papers are discussed in relation to this topic.
      RESULTS: Research suggests there is a disproportionately high number of
      individuals with ADHD involved with the Criminal Justice System. UK studies among
      offenders have indicated around 45% of youths and 24% of male adults screen
      positive for a childhood history of ADHD, 14% of whom have persisting symptoms in
      adulthood. Those with persisting symptoms have a significantly younger onset of
      offending and higher rate of recidivism. ADHD was the most powerful predictor of
      violent offending, even above substance misuse. They accounted for 8-fold more
      institutional aggressive behavioural disturbances (critical incidents) than other
      non-ADHD prisoners. Critical incidents have also been associated with personality
      disordered patients screening positive for ADHD and detained under the Mental
      Health Act. It is the impulsive symptoms and mood instability associated with
      ADHD that most likely increase the risk of critical incidents within
      institutional settings. CONCLUSIONS: There are international guidelines available
      for the treatment of ADHD; however, serious offenders with ADHD will require more
      complex and comprehensive interventions than their non-offending peers. In
      particular psychological interventions need to be provided that contain a
      prosocial competence component. One such programme, the R&R2 for ADHD Youths and
      Adults, has demonstrated improvement in ADHD symptoms, anxiety, depression,
      antisocial behaviour and social functioning at three month follow-up with medium
      to large effect sizes.

PMID- 21906011
TI  - Ex vivo differentiation of natural killer cells from human umbilical cord blood
      CD34+ progenitor cells.
AB  - Natural Killer (NK)-cells are peripheral blood lymphocytes that represent an
      important arm of the innate immune system. NK-cells play a critical role in the
      immune surveillance against tumors and virally infected cells in a major
      histocompatibiliy complex (MHC)-unrestricted fashion. We have explored such
      capacities of NK-cells after differentiation from hematopoietic stem and
      progenitor cells derived from human umbilical cord blood. Several culture
      conditions have been established supporting proliferation and subsequent
      differentiation of these cells in terms of receptor expression and specific lysis
      depending on the growth conditions in the presence and absence of supportive
      stromal feeders. We show that acquisition of Killer Immunoglobulin Receptor (KIR)
      as well as NK Cytotoxicity Receptor expressions is independent of culture
      condition whereas absence of stromal feeders did not support acquisition of
      CD94/NKG2A expression. Such KIR-positive/NKG2A-negative cells generated under
      different culture conditions showed strong and specific cytolytic activity which
      could have impact on further immunotherapeutic strategies.

PMID- 21906014
TI  - Recent patents on live bacteria and their products as potential anticancer
      agents.
AB  - This review intends to provide a comprehensive coverage of the various patents,
      published or issued, since 2007 on live or attenuated bacteria as potential
      anticancer agents, as well as microbial products including toxins, enzymes,
      antibiotics, various proteins and peptides as well as other small molecular
      weight products. Below is a list of such published/issued patents and a summary
      of the main contents of many such patents.

PMID- 21906013
TI  - Update on laser photochemotherapy: an alternative for cancer treatment.
AB  - Although major progress has been made in surgery, radiation, and chemotherapy for
      the treatment of malignancy during the last 20 years, there has been little
      improvement in the survival of patients with recurrent or advanced head and neck
      cancer. Because of the ease and accessibility for surgery and their loco-regional
      biological behavior, head and neck cancers serve as an ideal model to test
      combined laser energy delivered via interstitial fiberoptics and chemotherapeutic
      agents activated by photo-thermal energy as an alternative, less invasive
      treatment for cancer. A number of investigators have shown that anthracyclines
      and cisplatin are likely candidates for light or heat activation in cancer cells.
      Maximum tolerated dose followed by photochemical and thermal activation via laser
      fiberoptics can improve treatment by sensitizing tumor response. The higher
      intratumor drug levels compared to systemic drug administration along with laser
      activation should also reduce systemic toxicity. In this article the authors
      analyze the concept of combining anti-cancer drugs and laser therapy and review
      the clinical application. In summary, the literature available suggests
      photochemotherapy with currently approved drugs and lasers may soon become an
      attractive alternative for cancer treatment.

PMID- 21906015
TI  - Local use-dependent sleep; synthesis of the new paradigm.
AB  - The logic and potential mechanisms for a new paradigm, the local use-dependent
      view of sleep as a distributed dynamic process in brain, are presented. This new
      paradigm is needed because the current dominant top-down imposition of sleep on
      the brain by sleep regulatory centers is either silent or is of inadequate
      explanatory value for many well-known sleep phenomena, e.g. sleep inertia. Two
      mechanistic falsifiable hypotheses linking sleep to cell use and the emergence of
      sleep/wake states are presented. These hypotheses are not mutually exclusive and
      both firmly link sleep to activity-dependent epigenetic brain plasticity and the
      need to integrate and balance waking activity induced-network connectivity
      changes. The views presented herein emphasize the inseparability of sleep
      mechanisms from a connectivity sleep function.

PMID- 21906017
TI  - Synaptic potentiation and sleep need: clues from molecular and
      electrophysiological studies.
AB  - Sleep is homeostatically regulated in all species that have been carefully
      studied. In mammals and birds, the best characterized marker of sleep pressure is
      slow wave activity (SWA), defined as the electroencephalogram (EEG) power between
      0.5 and 4 Hz during NREM sleep. SWA peaks at sleep onset and decreases with time
      spent asleep, and reflects the synchronous firing of cortical neurons coordinated
      by an underlying slow oscillation, the fundamental cellular phenomenon of NREM
      sleep. We have recently proposed the synaptic homeostasis hypothesis of sleep,
      which claims that an important function of sleep is to maintain synaptic balance.
      This hypothesis states that plastic processes during wake are biased towards
      synaptic potentiation, resulting in a net increase in synaptic strength in many
      brain circuits. Such increased synaptic weight would be unsustainable in the long
      run, due to increased demand for energy, space and supplies, and risk of synaptic
      saturation. Thus, according to the synaptic homeostasis hypothesis, sleep is
      important to renormalize synaptic strength to a baseline level that is
      sustainable and beneficial for memory and performance. There is strong evidence
      that the amplitude and slope of EEG slow waves is related to the number of
      neurons that enter an up state or a down state of the slow oscillation near
      synchronously, and that synchrony is directly related to the number, strength,
      and efficacy of synaptic connections among them. Thus, the average synaptic
      strength (number or efficacy of synapses) reached in a given cortical area at the
      end of the major wake phase should be reflected by the level of SWA in the EEG at
      sleep onset. Moreover, according to the hypothesis, sleep SWA is not only a
      useful proxy of wake-related cortical synaptic strength, but could mediate the
      renormalization of neural circuits by favoring net synaptic depression, perhaps
      aided by low levels of norepinephrine, serotonin, and acetylcholine during NREM
      sleep. Here we briefly review human and animal studies showing that, consistent
      with this hypothesis, 1) in the adult cerebral cortex wake is associated with a
      net increase in synaptic strength, and sleep with a net decrease; and 2) SWA
      reflects not just prior "use" of specific neuronal circuits, but rather the
      occurrence of plastic changes, with increases in SWA after synaptic potentiation,
      and decreases in SWA after synaptic depression. We end by discussing current
      challenges to this hypothesis and future research directions.

PMID- 21906016
TI  - Sleep-active neuronal nitric oxide synthase-positive cells of the cerebral
      cortex: a local regulator of sleep?
AB  - Our recent report demonstrated that a small subset of GABAergic interneurons in
      the cerebral cortex of rodents expresses Fos protein, a marker for neuronal
      activity, during SWS [1]. The population of sleep-active neurons consists of
      strongly immunohistochemically-stained cells for the enzyme neuronal nitric oxide
      synthase (Type I cells). By virtue of their widespread localization within the
      cerebral cortex and their widespread projections to other cortical cell types,
      cortical neuronal nitric oxide synthase-positive neurons are positioned to play a
      central role in the local regulation of sleep waveforms within the cerebral
      cortex. Here, we review the possible functions of neuronal nitric oxide synthase
      and its diffusible gas product, nitric oxide, in regulating neuronal activity,
      synaptic plasticity and cerebral blood flow within the context of local sleep
      regulation in the cerebral cortex. We also summarize what is known, in addition
      to their expression of neuronal nitric oxide synthase, about the biochemical
      phenotype, synaptic connectivity and electrophysiological properties of this
      novel sleep-active population of cells. Finally, we raise some critical
      unanswered questions about the role of this population in local sleep regulation
      within the cerebral cortex and describe some experimental approaches that might
      be used to address those questions.

PMID- 21906018
TI  - Thalamocortical oscillations: local control of EEG slow waves.
AB  - This article starts with a brief review of the thalamocortical system
      architecture, which is composed of the projecting thalamic nuclei, the thalamic
      reticular nucleus, and the neocortex. Then we provide a description of the three
      states of vigilances followed by a detailed review of major brain rhythms present
      in the thalamocortical system, ranging from very slow to very fast oscillations.
      We provide descriptions of known mechanisms and hypotheses for unknown mechanisms
      for the generation of the different rhythms. The last part offers a detailed
      review on sleep slow oscillation describing its properties in the thalamocortical
      system, proposing a mechanism of generation of active states and a description of
      their propagation.

PMID- 21906019
TI  - Beyond the neuron: astroglial regulation of mammalian sleep.
AB  - The cellular substrates of sleep are incompletely described, but historically
      they have been thought to be neuronal. According to one view, sleep is produced
      by interactions between wake-promoting neurons, sleep-inducing neurons, and sleep
      inducing substances released by neurons (e.g. adenosine)[1, 2]. Alternatively,
      sleep pressure may arise independently among subsets of neurons in a use
      dependent fashion within the neocortex (i.e. 'local' sleep) [3, 4]. Implicit in
      both views is the notion that changes in neuronal activity (or plasticity) is the
      principle mechanism driving sleep homeostasis. Recent findings, however, suggest
      that the glial cells known as astrocytes may play critical roles in mammalian
      sleep.

PMID- 21906020
TI  - Assessment of network states: local hemodynamics.
AB  - Neural activity utilizes energy resources and requires replenishment of
      metabolites through vascular dilation. During wake, cortical neurons usually have
      depolarized membrane potentials and exhibit frequent spontaneous action
      potentials, requiring an increased metabolic delivery to activated tissue and
      causing blood vessels to dilate. Quiet sleep (QS) is characterized by alternating
      membrane potential between a depolarized and hyperpolarized state. The
      hyperpolarized state has a lower membrane potential and exhibits few action
      potentials, which may be less metabolically demanding. In order to investigate
      the relationship between evoked neural and metabolic responses across wake and
      sleep states, we combined electrical and optical imaging techniques. We implanted
      rats with screw electrodes to measure evoked response potentials (ERPs), and used
      a light emitting diode (LED) and photodiode to measure evoked changes in local
      hemodynamics based on hemoglobin absorption properties. During QS, hemodynamic
      changes were larger in amplitude compared to wake and rapid eye movement (REM)
      sleep. In this review, we explore the potential mechanisms for the larger
      hemodynamic changes. Wake periods may correspond to decreased vessel compliance
      as they expand to supply tissue with metabolites while sleep periods may decrease
      metabolic demand and allow vessels to relax and restore compliance.

PMID- 21906022
TI  - Going local: insights from EEG and stereo-EEG studies of the human sleep-wake
      cycle.
AB  - In the present paper, we reviewed a large body of evidence, mainly from
      quantitative EEG studies of our laboratory, supporting the notion that sleep is a
      local and use-dependent process. Quantitative analyses of sleep EEG recorded from
      multiple cortical derivations clearly indicate that every sleep phenomenon, from
      sleep onset to the awakening, is strictly local in nature. Sleep onset first
      occurs in frontal areas, and a frontal predominance of low-frequency power
      persists in the first part of the night, when the homeostatic processes mainly
      occur, and then it vanishes. Upon awakening, we showed an asynchronous EEG
      activation of different cortical areas, the more anterior ones being the first to
      wake up. During extended periods of wakefulness, the increase of sleepiness
      related low-EEG frequencies is again evident over the frontal derivations.
      Similarly, experimental manipulations of sleep length by total sleep deprivation,
      partial sleep curtailment or even selective slow-wave sleep deprivation lead to a
      slow-wave activity rebound localized especially on the anterior derivations.
      Thus, frontal areas are crucially involved in sleep homeostasis. According to the
      local use-dependent theory, this would derive from a higher sleep need of the
      frontal cortex, which in turn is due to its higher levels of activity during
      wakefulness. The fact that different brain regions can simultaneously exhibit
      different sleep intensities indicates that sleep is not a spatially global and
      uniform state, as hypothesized in the theory. We have also reviewed recent
      evidence of localized effects of learning and plasticity on EEG sleep measures.
      These studies provide crucial support to a key concept in the theory, the one
      claiming that local sleep characteristics should be use-dependent. Finally, we
      have reported data corroborating the notion that sleep is not necessarily present
      simultaneously in the entire brain. Our stereo-EEG recordings clearly indicate
      that sleep and wakefulness can co-exist in different areas, suggesting that
      vigilance states are not necessarily temporally discrete states. We conclude that
      understanding local variations in sleep propensity and depth, especially as a
      result of brain plasticity, may provide in the near future insightful hints into
      the fundamental functions of sleep.

PMID- 21906021
TI  - The cortical topography of local sleep.
AB  - In a recent series of experiments, we demonstrated that a visuomotor adaptation
      task, 12 hours of left arm immobilization, and rapid transcranial magnetic
      stimulation (rTMS) during waking can each induce local changes in the topography
      of electroencephalographic (EEG) slow wave activity (SWA) during subsequent non
      rapid eye movement (NREM) sleep. However, the poor spatial resolution of EEG and
      the difficulty of relating scalp potentials to the activity of the underlying
      cortex limited the interpretation of these results. In order to better understand
      local cortical regulation of sleep, we used source modeling to show that plastic
      changes in specific cortical areas during waking produce correlated changes in
      SWA during sleep in those same areas. We found that implicit learning of a
      visuomotor adaptation task induced an increase in SWA in right premotor and
      sensorimotor cortices when compared to a motor control. These same areas have
      previously been shown to be selectively involved in the performance of this task.
      We also found that arm immobilization resulted in a decrease in SWA in
      sensorimotor cortex. Inducing cortical potentiation with repetitive transcranial
      magnetic stimulation (rTMS) caused an increase in SWA in the targeted area and a
      decrease in SWA in the contralateral cortex. Finally, we report the first
      evidence that these modulations in SWA may be related to the dynamics of
      individual slow waves. We conclude that there is a local, plasticity dependent
      component to sleep regulation and confirm previous inferences made from the scalp
      data.

PMID- 21906024
TI  - Reciprocal interactions between wakefulness and sleep influence global and
      regional brain activity.
AB  - Reciprocal interactions between wakefulness and sleep substantially influence
      human brain function in both states of vigilance. On the one hand, there is
      evidence that regionally-specialized brain activity during wakefulness is
      modulated by the interaction between a local use-dependent buildup of homeostatic
      sleep pressure and circadian signals. On the other hand, brain activity during
      sleep, although mainly constrained by genuine sleep oscillations, shows wake
      dependent regionally-specific modulations, which are involved in the dissipation
      of local homeostatic sleep pressure and memory consolidation.

PMID- 21906025
TI  - State dissociation, human behavior, and consciousness.
AB  - Sleep is clearly not only a whole-brain or global phenomenon, but can also be a
      local phenomenon. This accounts for the fact that the primary states of being
      (wakefulness, NREM sleep, and REM sleep) are not necessarily mutually exclusive,
      and components of these states may appear in various combinations, with
      fascinating clinical consequences. Examples include: sleep inertia, narcolepsy,
      sleep paralysis, lucid dreaming, REM sleep behavior disorder, sleepwalking, sleep
      terrors, out-of-body experiences, and reports of alien abduction. The incomplete
      declaration of state likewise has implications for consciousness - which also has
      fluid boundaries. Fluctuations in the degree of consciousness are likely
      explained by abnormalities of a  "spatial and temporal binding rhythm" which
      normally results in a unified conscious experience. Dysfunctional binding may
      play a role in anesthetic states, autism, schizophrenia, and neurodegenerative
      disorders. Further study of the broad spectrum of dissociated states of sleep and
      wakefulness that are closely linked with states of consciousness and
      unconsciousness by basic neuroscientists, clinicians, and members of the legal
      profession will provide scientific, clinical and therapeutic insights, with
      forensic implications.

PMID- 21906023
TI  - A local, bottom-up perspective on sleep deprivation and neurobehavioral
      performance.
AB  - Waking neurobehavioral performance is temporally regulated by a sleep/wake
      homeostatic process and a circadian process in interaction with a time-on-task
      effect. Neurobehavioral impairment resulting from these factors is task-specific,
      and characterized by performance variability. Several aspects of these phenomena
      are not well understood, and cannot be explained solely by a top-down
      (subcortically driven) view of sleep/wake and performance regulation. We present
      a bottom-up theory, where we postulate that task performance is degraded by
      local, use-dependent sleep in neuronal groups subserving cognitive processes
      associated with the task at hand. The theory offers explanations for the temporal
      dependence of neurobehavioral performance on time awake, time on task, and their
      interaction; for the effectiveness of task switching and rest breaks to overcome
      the time-on-task effect (but not the effects of sleep deprivation); for the task
      specific nature of neurobehavioral impairment; and for the stochastic property of
      performance variability.

PMID- 21906026
TI  - Oxidative stress induced mitochondrial DNA deletion as a hallmark for the drug
      development in the context of the cerebrovascular diseases.
AB  - Oxidative stress in the cardiovascular system, including brain microvessels
      and/or parenchymal cells results in an accumulation of reactive oxygen species
      (ROS) and reactive nitrogen species (RNS) compounds thus promoting leukocyte
      adhesion and increasing endothelial permeability. The resulting chronic injury
      stimulus results in progressive cellular hypometabolism. We propose that
      hypometabolism, coupled with oxidative stressors, is responsible for most
      Alzheimer disease (AD) and cerebrovascular accidents (CVAs) and appears to be a
      central initiating factor for vascular abnormalities, mitochondrial damage and an
      imbalance in the activity of vasoactive substances, such as different isoforms of
      nitric oxide synthase (NOS), endothelin-1 (ET-1), oxidative stress markers, mtDNA
      and mitochondrial enzymes in the vascular wall and in brain parenchymal cells. At
      higher concentrations, ROS induces cell injury and death, which occurs during the
      aging process, where accelerated generation of ROS and a gradual decline in
      cellular antioxidant defense mechanisms, especially in the mitochondria. Vascular
      endothelial and neuronal mitochondria are especially vulnerable to oxidative
      stress due to their role in energy supply and use, which can cause a cascade of
      debilitating factors such as the production of giant and/or vulnerable young
      mitochondrion who's DNA has been compromised. Therefore, mitochondrial DNA
      abnormalities such as overproliferation and or deletion can be used as a key
      marker for diseases differentiation and effectiveness of the treatment. We
      speculate that specific antioxidants such as acetyl-L-carnitine and R-alpha
      lipoic acid seem to be potential treatments for AD. They target the factors that
      damage mitochondria and reverse its effect, thus eliminating the imbalance seen
      in energy production and restore the normal cellular function, making these
      antioxidants very powerful alternate strategies for the treatment of
      cardiovascular cerebrovascular as well as neurodegenerative diseases including
      AD. Future potential exploration using mtDNA markers can be considered more
      accurate hallmarks for diagnosis and monitoring treatment of human diseases. The
      present article discusses some of the patents regarding the oxidative stress.

PMID- 21906027
TI  - S6K inhibition renders cardiac protection against myocardial infarction through
      PDK1 phosphorylation of Akt.
AB  - In the present study, we observed a rapid and robust activation of the ribosomal
      protein S6K (S6 kinase) provoked by MI (myocardial infarction) in mice. As
      activation of S6K promotes cell growth, we hypothesized that increased S6K
      activity contributes to pathological cardiac remodelling after MI and that
      suppression of S6K activation may prevent aberrant cardiac remodelling and
      improve cardiac function. In mice, administration of rapamycin effectively
      suppressed S6K activation in the heart and significantly improved cardiac
      function after MI. The heart weight/body weight ratio and fibrotic area were
      substantially reduced in rapamycin-treated mice. In rapamycin-treated mice,
      decreased cardiomyocyte remodelling and cell apoptosis were observed compared
      with vehicle-treated controls. Consistently, inhibition of S6K with PF-4708671
      displayed similar protection against MI as rapamycin. Mechanistically, we
      observed significantly enhanced Thr308 phosphorylation and activation of Akt in
      rapamycin- and PF-4708671-treated hearts. Cardiomyocyte-specific deletion of PDK1
      (phosphoinositide-dependent kinase 1) and Akt1/3 abolished cardioprotection after
      MI in the presence of rapamycin administration. These results demonstrate that
      S6K inhibition rendered beneficial effects on left ventricular function and
      alleviated adverse remodelling following MI in mice by enhancing Akt signalling,
      suggesting the therapeutic value of both rapamycin and PF-4708671 in treating
      patients following an MI.

PMID- 21906028
TI  - Hypertonic stress regulates amino acid transport and cell cycle proteins in chick
      embryo hepatocytes.
AB  - Hyperosmotic stress affects cell growth, decreasing cell volume and increasing
      the uptake of organic osmolytes. However, the sensitivity of embryonic cells to
      osmotic treatment remains to be established. We have analysed some aspects of
      cell-cycle control and amino-acid transport in hypertonic conditions during
      prenatal life. The effects of hyperosmotic stress on amino-acid uptake mediated
      by system A, (3)H-thymidine incorporation, and regulation of cell-cycle proteins
      were analysed in chick embryo hepatocytes. Hypertonic stress increased system A
      activity and caused cell-cycle delay. Effects on amino-acid transport involved
      p38 kinase activation and new carrier synthesis. Cyclin D1, cdk4 (cyclin
      dependent kinase 4) and PCNA (proliferating-cell nuclear antigen) levels
      decreased, whereas cyclin E, p21 and p53 levels were unchanged. Incorporation of
      (3)H-leucine indicated decreased synthesis of cyclin D1. In contrast, analysis of
      mRNA by qRT-PCR (quantitative real-time PCR) showed a net increase of cyclin D1
      transcripts, suggesting post-transcriptional regulation. The data show that chick
      embryo hepatocytes respond to hyperosmotic conditions by arresting cell growth to
      prevent DNA damage and increasing osmolyte uptake to regulate cell volume,
      indicating that the adaptive response to environmental stress exists during
      prenatal life.

PMID- 21906029
TI  - Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue
      syndromes.
AB  - Several studies recognized an overlap between CFS (chronic fatigue syndrome) and
      POTS (postural tachycardia syndrome). We compared the autonomic and neurohormonal
      phenotype of POTS patients with CFS (CFS-POTS) to those without CFS (non-CFS
      POTS), to determine whether CFS-POTS represents a unique clinical entity with a
      distinct pathophysiology. We recruited 58 patients with POTS, of which 47 were
      eligible to participate. A total of 93% of them reported severe fatigue [CIS
      (Checklist of Individual Strength), fatigue subscale >36], and 64% (n=30)
      fulfilled criteria for CFS (CFS-POTS). The prevalence of CFS symptoms (Centers
      for Disease Control and Prevention criteria) was greater in the CFS-POTS group,
      but the pattern of symptoms was similar in both groups. Physical functioning was
      low in both groups (RAND-36 Health Survey, 40+/-4 compared with 33+/-3; P=0.153),
      despite more severe fatigue in CFS-POTS patients (CIS fatigue subscale 51+/-1
      compared with 43+/-3; P=0.016). CFS-POTS patients had greater orthostatic
      tachycardia than the non-CFS-POTS group (51+/-3 compared with 40+/-4 beats/min;
      P=0.030), greater low-frequency variability of BP (blood pressure; 6.3+/-0.7
      compared with 4.8+/-1.0 mmHg2; P=0.019), greater BP recovery from early to late
      phase II of the Valsalva manoeuvre (18+/-3 compared with 11+/-2 mmHg; P=0.041)
      and a higher supine (1.5+/-0.2 compared with 1.0+/-0.3 ng/ml per.h; P=0.033) and
      upright (5.4+/-0.6 compared with 3.5+/-0.8 ng/ml per h; P=0.032) PRA (plasma
      renin activity). In conclusion, fatigue and CFS-defining symptoms are common in
      POTS patients. The majority of them met criteria for CFS. CFS-POTS patients have
      higher markers of sympathetic activation, but are part of the spectrum of POTS.
      Targeting this sympathetic activation should be considered in the treatment of
      these patients.

PMID- 21906030
TI  - OP9-DL1 cell co-culture enhances anti-tumour immunity of mouse bone marrow
      derived dendritic cells.
AB  - DCs (dendritic cells) are the strongest professional APCs (antigen-presenting
      cells) to initiate immune responses against pathogens, but they are usually
      incompetent in initiating efficient immune responses in the progress of solid
      tumours. We have shown that Notch signalling plays a pivotal role in DC-dependent
      anti-tumour immunity. Compared with the control DCs, OP9-DL1 (Delta-like1) cell
      co-cultured DCs gained increased tumour suppression activity when inoculated
      together with tumour cells. This was probably due to the activation of Notch
      signalling in DCs enhancing their ability to evoke anti-tumour immune responses
      in solid tumours. Indeed, the OP9-DL1 cell co-cultured DCs expressed higher
      levels of MHC I, MHC II, CXCR4 (CXC chemokine receptor 4), CCR7 (CC chemokine
      receptor 7), IL-6 (interleukin 6), IL-12 and TNFalpha (tumour necrosis factor
      alpha), and a lower level of IL-10 than control DCs, resulting in more efficient
      DC migration and T-cell activation in vivo and in vitro. T-cells stimulated by
      OP9-DL1 cells co-cultured DCs more efficiently; and were cytotoxic against tumour
      cells, in contrast with control DCs. These results indicated that up-regulation
      of Notch signalling in DCs by co-culturing with OP9-DL1 cells enhances DC
      dependent anti-tumour immune reactions, making the Notch signalling pathway a
      target for the establishment of the DC-based anti-tumour immunotherapies.

PMID- 21906031
TI  - The conflicting meaning of transparency.

PMID- 21906034
TI  - Profile of Sheena Josselyn. Interviewed by Kristie Nybo.

PMID- 21906036
TI  - A decade after the genome, bioinformatics comes of age.

PMID- 21906037
TI  - Clone selection in weakly adherent cells.

PMID- 21906038
TI  - Minor variant detection in amplicons using 454 massive parallel pyrosequencing:
      experiences and considerations for successful applications.
AB  - Ultra-deep sequencing (UDS) of amplicons is a major application for next
      generation sequencing technologies, even more so for the 454 Genome Sequencer
      FLX. Especially for this application, errors that might be introduced during any
      of the sample processing or data analysis steps should be avoided or at least
      recognized, as they might lead to aberrant sequence variant calling. Since 454
      pyrosequencing relies on PCR-driven target amplification, it is key to
      differentiate errors introduced during the amplification step from genuine
      minority variants. Thereto, optimal primer design is imperative because primer
      selection, primer dimer formation, and nonspecific binding may all affect the
      quality and outcome of amplicon-based deep sequencing. Also, other intrinsic PCR
      characteristics including amplification drift and the formation of secondary
      structures may influence sequencing data quality. We illustrate these phenomena
      using real life case studies and propose experimental and analytical evidence
      based solutions for effective practice. Furthermore, because accuracy of the DNA
      polymerase is vital for reliable UDS results, a comparative analysis of error
      profiles from seven different DNA polymerases was performed and experimentally
      assessed in parallel by 454 sequencing. Finally, intra and interrun variability
      evaluation of the 454 sequencing protocol revealed highly reproducible results in
      amplicon-based UDS.

PMID- 21906039
TI  - The use of melting curves as a novel approach for validation of real-time PCR
      instruments.
AB  - Validation of PCR thermal cycler performance is crucial in order to obtain
      reliable results. In this study, high resolution melting curve (HRM) analysis is
      presented as a novel validation method for real-time PCR instruments. By applying
      HRM analysis using a defined PCR amplicon and EvaGreen dye, information about the
      temperature accuracy and thermal homogeneity of the heating block was obtained.
      This pilot study shows the potential of our technique for temperature validation
      of real-time quantitative PCR thermal cyclers. Our data correlated well with the
      temperature accuracy data obtained from the Mobile Temperature Acquisition System
      (MTAS; r2 = 0.93), which conforms to the National Institute of Standards and
      Technology criteria, and our method was reproducible in independent runs (r2 =
      0.95). The advantages of this HRM-based method include: (i) temperature
      measurement under real world conditions in the reaction liquid in closed reaction
      tubes; (ii) temperature measurement of all wells; and (iii) applicability to all
      real-time PCR instruments capable of HRM analysis.

PMID- 21906040
TI  - In-solution staining and arraying method for the immunofluorescence detection of
      gammaH2AX foci optimized for clinical applications.
AB  - Immunofluorescence quantification of gammaH2AX foci is a powerful approach to
      quantify DNA double-strand breaks induced by cancer therapy or accidental
      exposure to ionizing radiation. Here we report a modification to the gammaH2AX
      immunofluorescence labeling method, whereby cells are stained in-solution before
      being spotted and fixed onto microscope slides. Our modified method allows
      arraying of 16 patient samples/slide ready for foci counting in 2 h and
      demonstrated reliably detection of gammaH2AX foci in mononuclear cells prepared
      from patients who had undergone radiation therapy.

PMID- 21906041
TI  - The fluorescent dyes TO-PRO-3 and TOTO-3 iodide allow detection of microbial
      cells in soil samples without interference from background fluorescence.
AB  - Visualization of microorganisms in soils and sediments using fluorescent dyes is
      a common method in microbial ecology studies, but is often hampered by strong
      nonspecific background fluorescence that can mask genuine cellular signals. The
      cyanine nucleic acid binding dyes TO-PRO-3 and TOTO-3 iodide enabled a clear
      detection of microbial cells in a mineral soil, while nonspecific background was
      greatly reduced compared with commonly used dyes. When used as counterstains for
      fluorescence in situ hybridization (FISH), both cyanine dyes allowed
      identification of microbial cells despite strong background from nonspecifically
      bound probes. TO-PRO-3 and TOTO-3 are easy to use and represent superior
      alternatives for detecting microorganisms in soil environments.

PMID- 21906042
TI  - A strategy for purifying glutathione S-transferase in the presence of sodium
      dodecyl sulfate.
AB  - Glutathione S-transferase (GST) is widely used to prepare and purify GSTtagged
      fusion proteins. Although GST improves protein solubility, detergents must often
      be used to achieve protein solubilization from bacterial lysates. However,
      purification of GST by affinity chromatography cannot be achieved in the presence
      of even low concentrations of the detergent sodium dodecyl sulfate (SDS). Here we
      show that 2-methyl-2,4-pentanediol (MPD) can prevent SDS from interfering with
      purification of GST, thus enabling purification of proteins that require SDS to
      improve their solubility.

PMID- 21906043
TI  - A rapid and cost-effective method for sequencing pooled cDNA clones by using a
      combination of transposon insertion and Gateway technology.
AB  - Large-scale cDNA-sequencing projects require an efficient strategy for mass
      sequencing. Here we describe a method for sequencing pooled cDNA clones using a
      combination of transposon insertion and Gateway technology. Our method reduces
      the number of shotgun clones that are unsuitable for reconstruction of cDNA
      sequences, and has the advantage of reducing the total costs of the sequencing
      project.

PMID- 21906045
TI  - Age-related penetrance of hereditary atypical hemolytic uremic syndrome.
AB  - Hereditary atypical hemolytic uremic syndrome (aHUS), a dramatic disease
      frequently leading to dialysis, is associated with germline mutations of the CFH,
      CD46, or CFI genes. After identification of the mutation in an affected aHUS
      patient, single-site gene testing of relatives is the preventive care
      perspective. However, clinical data for family counselling are scarce. From the
      German-Speaking-Countries-aHUS-Registry, 33 index patients with mutations were
      approached for permission to offer relatives screening for their family-specific
      mutations and to obtain demographic and clinical data. Mutation screening was
      performed using direct sequencing. Age-adjusted penetrance of aHUS was calculated
      for each gene in index cases and in mutation-positive relatives. Sixty-one
      relatives comprising 41 parents and 20 other relatives were enrolled and
      mutations detected in 31/61. In total, 40 research participants had germline
      mutations in CFH, 19 in CD46 and in 6 CFI. Penetrance at age 40 was markedly
      reduced in mutation-positive relatives compared to index patients overall with
      10% versus 67% (P < 0.001); 6% vs. 67% (P < 0.001) in CFH mutation carriers and
      21% vs. 70% (P= 0.003) in CD46 mutation carriers. Age-adjusted penetrance for
      hereditary aHUS is important to understand the disease, and if replicated in the
      future, for genetic counselling.

PMID- 21906046
TI  - Investigating epilepsy in Africa: 10 years of data collection using a
      standardized questionnaire in 2,269 peoples with epilepsy.
AB  - PURPOSE: The need for comparable epidemiologic data on epilepsy from various
      locations in tropical areas has led in 1994 to the creation of a questionnaire
      able to standardize information. The Limoges' questionnaire was created to
      collect information independently of the objectives of each survey performed, and
      since it has been employed in various continents under tropics latitude. In
      Africa between 1994 and 2004, 13 epidemiologic surveys in 12 countries were
      performed by this means. Authors of these works were solicited to communicate
      their raw data on people with epilepsy (PWE). METHODS: Information collected was
      aggregated in a database upon which operations of data management were processed.
      Undernutrition status was determined using an anthropologic method, according
      World Health Organization (WHO) recommendations. Factors associated with
      undernutrition and absence of treatment by phenobarbitone were searched for by
      using multivariate logistic regression. KEY FINDINGS: Information about 2,269 PWE
      was collected. Mean treatment gap and undernutrition were determined,
      respectively, to be 30.6% [95% confidence interval (95% CI) 28.7-32.6] and 25.4%
      (95% CI 22.7-28.2). Factors significantly associated with undernutrition and not
      being treated with phenobarbitone were determined. SIGNIFICANCE: Despite the
      different purposes of each study, we were able to pool information in order to
      characterize and study particular traits of PWE in Africa. Some items of
      particular importance should be collected systematically and will be highlighted
      in a newer version of this questionnaire. Because many surveys were undertaken
      using this tool in tropical areas, a backward compatibility should be ensured.

PMID- 21906047
TI  - A novel deletion in ZBTB24 in a Lebanese family with immunodeficiency,
      centromeric instability, and facial anomalies syndrome type 2.
AB  - The immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome
      is a rare autosomal recessive disease characterized by targeted chromosome
      breakage, directly related to a genomic methylation defect. It manifests with
      phenotypic and clinical variability, with the most consistent features being
      developmental delay, facial anomalies, cytogenetic defects and immunodeficiency
      with a reduction in serum immunoglobulin levels. From the molecular point of
      view, ICF syndrome was always divided into ICF type I (ICF1) and ICF type 2
      (ICF2). Mutations in DNMT3B gene are responsible for ICF1, while mutations in
      ZBTB24 have been reported to be responsible for ICF2. In this study, we describe
      a Lebanese family with three ICF2 affected brothers. Sanger sequencing of the
      coding sequence of ZBTB24 gene was conducted and revealed a novel deletion:
      c.396_397delTA (p.His132Glnfs*19), resulting in a loss-of-function of the
      corresponding protein. ZBTB24 belongs to a large family of transcriptional
      factors and may be involved in DNA methylation of juxtacentromeric DNA. Detailed
      molecular and functional studies of the ZBTB24 and DNMT3B genes are needed to
      understand the pathophysiology of ICF syndrome.

PMID- 21906048
TI  - Mapping a mouse limbic seizure susceptibility locus on chromosome 10.
AB  - PURPOSE: Mapping seizure susceptibility loci in mice provides a framework for
      identifying potentially novel candidate genes for human epilepsy. Using C57BL/6J
      * A/J chromosome substitution strains (CSS), we previously identified a locus on
      mouse chromosome 10 (Ch10) conferring susceptibility to pilocarpine, a muscarinic
      cholinergic agonist that models human temporal lobe epilepsy by inducing initial
      limbic seizures and status epilepticus (status), followed by hippocampal cell
      loss and delayed-onset chronic spontaneous limbic seizures. Herein we report
      further genetic mapping of pilocarpine quantitative trait loci (QTLs) on Ch10.
      METHODS: Seventy-nine Ch10 F(2) mice were used to map QTLs for duration of
      partial status epilepticus and the highest stage reached in response to
      pilocarpine. Based on those results we created interval-specific congenic lines
      to confirm and extend the results, using sequential rounds of breeding
      selectively by genotype to isolate segments of A/J Ch10 genome on a B6
      background. KEY FINDINGS: Analysis of Ch10 F(2) genotypes and seizure
      susceptibility phenotypes identified significant, overlapping QTLs for duration
      of partial status and severity of pilocarpine-induced seizures on distal Ch10.
      Interval-specific Ch10 congenics containing the susceptibility locus on distal
      Ch10 also demonstrated susceptibility to pilocarpine-induced seizures, confirming
      results from the F(2) mapping population and strongly supporting the presence of
      a QTL between rs13480781 (117.6 Mb) and rs13480832 (127.7 Mb). SIGNIFICANCE: QTL
      mapping can identify loci that make a quantitative contribution to a trait, and
      eventually identify the causative DNA-sequence polymorphisms. We have mapped a
      locus on mouse Ch10 for pilocarpine-induced limbic seizures. Novel candidate
      genes identified in mice can be investigated in functional studies and tested for
      their role in human epilepsy.

PMID- 21906049
TI  - Abnormalities of lexical and semantic processing in left temporal lobe epilepsy:
      an fMRI study.
AB  - PURPOSE: We examined the efficiency of lexical and semantic processing and
      associated brain activation using functional magnetic resonance imaging (fMRI) in
      patients with left temporal lobe epilepsy (TLE). METHODS: Twenty patients with
      left TLE (10 with hippocampal sclerosis, the HS group; and 10 with nonlesional MR
      scans, the NL group) and 12 healthy controls underwent an event-related fMRI
      analysis during a lexical decision task (LDT). Lexical and semantic processing
      were examined by comparing behavioral and imaging data associated with words and
      nonwords (lexicality) or with concrete and abstract words (concreteness). KEY
      FINDINGS: Although the control group showed greater activation associated with
      word stimuli than with nonword stimuli in a bilateral language network, both TLE
      groups showed greater activation for nonword stimuli than word stimuli, including
      greater activation of inferior frontal language areas (bilaterally in the HS
      group and left-lateralized in the NL group). The TLE groups also exhibited
      differential activation patterns during the processing of abstract and concrete
      words compared to controls, and compared to each other. For abstract words, in
      particular, the HS group showed activation of frontal areas typically associated
      with executive functions, whereas the NL group showed activation of more
      posterior semantic processing regions. SIGNIFICANCE: These results suggest that
      left TLE is associated with altered functional organization of cortical networks
      involved in lexical and semantic processing. In addition, the organization
      observed varies as a function of hippocampal pathology.

PMID- 21906050
TI  - Isovaline, a rare amino acid, has anticonvulsant properties in two in vitro
      hippocampal seizure models by increasing interneuronal activity.
AB  - PURPOSE: We investigated whether RS-isovaline, a unique amino acid found in
      carbonaceous meteorites and presumed extraterrestrial, has anticonvulsant
      properties in rat hippocampal slices in vitro. METHODS: Extracellular recordings
      were obtained in the rat hippocampal CA1 pyramidal layer in two in vitro seizure
      models: perfusion of low (0.25 mm) Mg(2+) and high (5 mm) K(+) (LM/HK), or 100
      MUm 4-aminopyridine (4-AP). To investigate the underlying mechanisms of isovaline
      action, whole-cell recordings were obtained from CA1 pyramidal neurons and
      stratum oriens interneurons during 4-AP blockade of K(+) channels. KEY FINDINGS:
      Perfusion of LM/HK produced seizure-like events (SLEs) or stimulus-evoked primary
      afterdischarges (PADs) with amplitudes of 0.9 +/- 0.1 mV lasting 80 +/- 14 s.
      Application of isovaline (250 MUm) for 20-30 min abolished SLEs and PADs or
      attenuated seizure amplitude and duration by 57.0 +/- 9.0% and 57.0 +/- 12.0%,
      respectively. Similar effects were seen with isovaline in the 4-AP seizure model.
      Isovaline alone increased interneuronal spontaneous spiking from 0.9 +/- 0.3 to
      3.2 +/- 0.9 Hz, increased input resistance by 21.6 +/- 8.1%, and depolarized the
      resting membrane potential by 8.0 +/- 1.5 mV; no changes in the firing or
      electrical properties of pyramidal neurons were observed. Coapplication of 4-AP
      and isovaline increased interneuronal spontaneous spiking from 1.0 +/- 0.6 to 2.6
      +/- 0.8 Hz, whereas pyramidal neuronal spiking activity decreased from 0.6 +/-
      0.4 to 0.2 +/- 0.1 Hz. SIGNIFICANCE: Isovaline exhibited anticonvulsant
      properties in two hippocampal seizure models. This may lead to the development of
      a new class of anticonvulsants based on an unusual mechanism of action of this
      presumed extraterrestrial amino acid.

PMID- 21906051
TI  - Differential effects of atorvastatin treatment and withdrawal on
      pentylenetetrazol-induced seizures.
AB  - PURPOSE: Statins are selective inhibitors of 3-hydroxyl-3-methyl-glutaryl
      coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme of the mevalonate
      pathway for cholesterol biosynthesis. Increasing evidence indicates that statins,
      particularly atorvastatin, are neuroprotective in several conditions, including
      stroke, cerebral ischemia, traumatic brain injury, and excitotoxic amino acid
      exposure. However, only a few studies have investigated whether statins modulate
      seizure activity. In the current study we investigated whether atorvastatin or
      simvastatin alters the seizures induced by pentylenetetrazol (PTZ), a classical
      convulsant. METHODS: Adult male Wistar rats were treated with atorvastatin or
      simvastatin for 7 days (10 mg/kg/day). Seizure activity was induced by PTZ (60
      mg/kg, i.p.), and evaluated by behavioral and electrographic methods. Cholesterol
      levels were determined by a standard spectrophotometric method. Blood-brain
      barrier (BBB) permeability was assessed by the fluorescein method. Atorvastatin
      levels in the plasma and cerebral cortex were determined by high-performance
      liquid chromatography tandem mass spectrometry. KEY FINDINGS: We found that oral
      atorvastatin treatment increased the latency to PTZ-induced generalized seizures.
      In contrast, when the 7-day atorvastatin treatment was withheld for 1 day (i.e.,
      atorvastatin withdrawal), PTZ-induced seizures were facilitated, as evidenced by
      a decrease in the latency to clonic and generalized tonic-clonic seizures induced
      by PTZ. In contrast, simvastatin treatment for 7 days (10 mg/kg/day, p.o.), with
      or without withdrawal, did not alter PTZ-induced seizures. Interestingly, the
      effects of atorvastatin treatment and withdrawal were not accompanied by changes
      in plasma or cerebral cortex cholesterol levels or in the BBB permeability.
      Atorvastatin levels in the plasma and cerebral cortex after 7 days of treatment
      were above the half maximal inhibitory concentration for inhibition of HMG-CoA
      reductase, whereas atorvastatin was not detectable in the plasma or cerebral
      cortex following a 24 h washout period (atorvastatin withdrawal). SIGNIFICANCE:
      We conclude that atorvastatin treatment and withdrawal have differential effects
      on pentylenetetrazol-induced seizures, which are not related to changes in plasma
      or cerebral cortex cholesterol levels or in BBB permeability. Additional studies
      are necessary to evaluate the molecular mechanisms underlying our findings as
      well as its clinical implications.

PMID- 21906053
TI  - Scuba diving is not associated with high prevalence of headache: a cross
      sectional study in men.
AB  - OBJECTIVE: To study the prevalence of cephalalgia in male divers. BACKGROUND:
      Scuba divers work in stressing environments and have a high cerebrovascular risk,
      both conditions which are supposed to contribute to the genesis of cephalalgia.
      However, no study assessed expressly the prevalence of cephalalgia in divers, to
      date. METHODS: We enrolled 201 professional male scuba divers (41.0 +/- 7.2
      years) and controls (41.1 +/- 7.2 years), and the risk ratio and its
      corresponding 95% confidence of suffering from cephalalgia was calculated.
      RESULTS: We found that 16% of divers and 22% of matched controls were affected by
      cephalalgia (P > .05), accounting for a risk ratio of 0.71 (95% CI 0.47-1.07).
      Divers reported fewer attacks per month (1.8 +/- 0.7, n = 32) with regard to
      controls (2.5 +/- 1.8, n = 45) (P = .02), but no differences concerning age at
      onset and severity were detected (P > .05). Divers suffered from migraine,
      migraine with aura and tension headache as much as controls. CONCLUSION: Scuba
      diving, an intense physical activity characterized by cerebral micro-vascular
      distress, is not associated with cephalalgia, as a whole, or migraine, tension
      headache or migraine with aura, more commonly than in a matched, non-diving,
      population. A longitudinal study may disclose if diving may act as a protective
      factor in the occurrence of crises of cephalalgia.

PMID- 21906052
TI  - Seizure-related cardiac repolarization abnormalities are associated with ictal
      hypoxemia.
AB  - PURPOSE: Cardiac arrhythmias and respiratory disturbances have been proposed as
      likely causes for sudden unexpected death in epilepsy. Oxygen desaturation occurs
      in one-third of patients with localization-related epilepsy (LRE) undergoing
      inpatient video-electroencephalography (EEG) telemetry (VET) as part of their
      presurgical workup. Ictal-related oxygen desaturation is accompanied by
      hypercapnia. Both abnormal lengthening and shortening of the corrected QT
      interval (QTc) on electrocardiography (ECG) have been reported with seizures. QTc
      abnormalities are associated with increased risk of sudden cardiac death. We
      hypothesized that there may be an association between ictal hypoxemia and cardiac
      repolarization abnormalities. METHODS: VET data from patients with refractory LRE
      were analyzed. Consecutive patients having at least one seizure with accompanying
      oxygen desaturation below 90% and artifact-free ECG data were selected. ECG
      during the 1 min prior to seizure onset (PRE) and during the ictal/postictal
      period with accompanying oxygen desaturation below 90% (DESAT) was analyzed.
      Consecutive QT and RR intervals were measured. In the same patients, DESAT
      seizures were compared with seizures without accompanying oxygen desaturation
      below 90% (NODESAT). For NODESAT seizures, QT and RR intervals for 2 min after
      seizure onset were measured. KEY FINDINGS: Thirty-seven DESAT seizures were
      analyzed in 17 patients with localization-related epilepsy. A total of 2,448 QT
      and RR intervals were analyzed during PRE. During DESAT, 1,554 QT and RR
      intervals were analyzed. Twelve of the 17 patients had at least one NODESAT
      seizure. A total of 19 NODESAT seizures were analyzed, including 1,558 QT and RR
      intervals during PRE and 3,408 QT and RR intervals during NODESAT. The odds ratio
      for an abnormally prolonged (>457 ms) QTcH (Hodges correction method) during
      DESAT relative to PRE was 10.64 (p < 0.0001). The odds ratio for an abnormally
      shortened (<372 ms) QTcH during DESAT relative to PRE was 1.65 (p < 0.0001).
      Seizure-related shortening and prolongation of QTc during DESAT were also
      observed when Fridericia correction of the QT was applied. During DESAT seizures,
      the mean range of QT values (QTr) (61.14 ms) was significantly different from
      that during PRE (44.43 ms) (p = 0.01). There was a significant association
      between DESAT QTr and oxygen saturation nadir (p = 0.025) and between DESAT QTr
      and duration of oxygen desaturation (p < 0.0001). Both QTcH prolongation and
      shortening also occurred with NODESAT seizures. A seizure-associated prolonged
      QTcH was more likely during DESAT than NODESAT, with an odds ratio of 4.30 (p <
      0.0001). A seizure-associated shortened QTcH was more likely during DESAT than
      NODESAT with an odds ratio of 2.13 (p < 0.0001). SIGNIFICANCE: We have shown that
      the likelihood of abnormal QTcH prolongation is increased 4.3-fold with seizures
      that are associated with oxygen desaturation when compared with seizures that are
      not accompanied with oxygen desaturation. The likelihood of abnormally shortened
      QTcH increases with seizures that are accompanied by oxygen desaturation with an
      odds ratio of 2.13 compared with that in seizures without desaturations. There is
      a significant association between the depth and duration of oxygen desaturation
      and QTr increase. These findings may be related to the pathophysiology of SUDEP.

PMID- 21906054
TI  - Does low atmospheric pressure independently trigger migraine?
AB  - Although atmospheric weather changes are often listed among the common migraine
      triggers, studies to determine the specific weather component(s) responsible have
      yielded inconsistent results. Atmospheric pressure change produces air movement,
      and low pressure in particular is associated with warm weather, winds, clouds,
      dust, and precipitation, but how this effect might generate migraine is not
      immediately obvious. Humans are exposed to low atmospheric pressure in situations
      such as ascent to high altitude or traveling by airplane in a pressurized cabin.
      In this brief overview, we consider those conditions and experimental data
      delineating other elements in the atmosphere potentially related to migraine
      (such as Saharan dust). We conclude that the available data suggest low
      atmospheric pressure unaccompanied by other factors does not trigger migraine.

PMID- 21906056
TI  - Periodontal regeneration following implantation of cementum and periodontal
      ligament-derived cells.
AB  - BACKGROUND AND OBJECTIVE: The periodontal regeneration of bone defects is often
      unsatisfactory and could be largely improved by cell therapy. Therefore, the
      purpose of this study was to evaluate the regenerative potential of implanting
      canine cementum-derived cells (CDCs) and canine periodontal ligament-derived
      cells (PDLDCs) in experimentally created periodontal intrabony defects in beagle
      dogs. MATERIAL AND METHODS: Cells were obtained from premolars extracted from
      four beagle dogs. Three-wall intrabony periodontal defects, 3 mm wide and 4 mm
      deep, were surgically created in their second and fourth premolars and plaque was
      allowed to accumulate. Once the defects were surgically debrided, periodontal
      regeneration was attempted by random implantation of collagen sponges embedded
      with 750,000 CDCs, 750,000 PDLDCs or culture medium. After 3 mo of healing,
      specimens were obtained and periodontal regenerative outcomes were assessed
      histologically and histometrically. RESULTS: The histological analysis showed
      that a minimal amount of new cementum was formed in the control group (1.56 +/-
      0.39 mm), whereas in both test groups, significantly higher amounts of new
      cementum were formed (3.98 +/- 0.59 mm in the CDC group and 4.07 +/- 0.97 mm in
      the PDLDC group). The test groups also demonstrated a larger dimension of new
      connective tissue, resulting in a significantly more coronal level of
      histological attachment. CONCLUSION: This proof-of-principle study suggests that
      cellular therapy, in combination with a collagen sponge, promoted periodontal
      regeneration in experimental intrabony periodontal defects.

PMID- 21906057
TI  - Association of the FcgammaRIIB-nt645+25A/G polymorphism with the expression level
      of the FcgammaRIIb receptor, the antibody response to Porphyromonas gingivalis
      and the severity of periodontitis.
AB  - BACKGROUND AND OBJECTIVE: Human FcgammaRIIb is an immunoglobulin G (IgG) receptor
      that inhibits the activation of B lymphocytes through cross-linking with the B
      cell receptor via immune complexes. This function acts as a negative regulator of
      antibody production. Our previous studies have demonstrated the gene
      polymorphisms in FcgammaRIIb to be associated with periodontitis. In this study,
      we presented a polymorphism--FcgammaRIIB-nt645+25A/G (rs2125685)--in intron 4 and
      analyzed its functional relevance to periodontitis. We examined whether the
      FcgammaRIIB-nt645+25A/G polymorphism is associated with periodontal parameters,
      the IgG response to the periodontopathic bacterium Porphyromonas gingivalis
      and/or the expression level of FcgammaRIIb on peripheral B lymphocytes. MATERIAL
      AND METHODS: Thirty-two patients with chronic periodontitis were genotyped with
      nested PCR and by direct sequencing of genome DNA. The levels of serum IgG and of
      specific IgG subclasses for P. gingivalis sonicate and for the recombinant 40-kDa
      outer membrane protein (OMP) were determined. The expression levels of
      FcgammaRIIb on peripheral B lymphocytes from 19 healthy donors were measured by
      flow cytometry. RESULTS: Patients with the FcgammaRIIB-nt645+25AA genotype showed
      significantly higher mean clinical attachment levels compared to patients with
      the FcgammaRIIB-nt645+25GG genotype (p = 0.003) and a significantly lower IgG
      response to P. gingivalis sonicate and to the 40-kDa OMP. The expression levels
      of FcgammaRIIb protein on the cell surface in peripheral B lymphocytes were
      higher in healthy donors with the FcgammaRIIB-nt645+25AA genotype than in those
      with the FcgammaRIIB-nt645+25GG genotype (p = 0.03). CONCLUSION: The higher
      expression levels of FcgammaRIIb in subjects with the FcgammaRIIB-nt645+25AA
      genotype may induce a lower level of production of IgG against P. gingivalis and
      therefore more severe periodontitis.

PMID- 21906058
TI  - Hip dysplasia.

PMID- 21906059
TI  - Treatment of hip dysplasia.
AB  - Hip dysplasia is a common orthopaedic developmental disorder of dogs. This paper
      reviews the treatment options available for management of the condition in the
      skeletally immature and adult dog.

PMID- 21906060
TI  - Extraction of urethral calculi by transabdominal cystoscopy and urethroscopy in
      nine dogs.
AB  - OBJECTIVES: To describe a minimally invasive technique for treating urethral
      obstructions in male dogs and to review the postoperative results. METHODS: All
      dogs (n=9) had urethral obstruction due to calculi. Obstructions were verified by
      radiographic and ultrasonographic examinations. Dogs with impaired kidney
      function were not included in the study. A 5-mm diameter trocar and cannula were
      placed in the ventral midline, 2 cm cranial to the umbilicus, allowing placement
      of a 10-mm diameter cannula under visual guidance, adjacent to the apex of the
      bladder. The bladder was then partially exteriorised and sutured to the skin. A 5
      mm diameter cystoscopy sheath was introduced into the bladder lumen and advanced
      into the urethra. Continuous retrograde flushing was used to dislodge the calculi
      from the site of obstruction and collect them upstream. RESULTS: The nine dogs
      were followed up for a minimum of 6 months. No major postoperative complications
      were identified. One dog exhibited transient macroscopic haematuria (for 3 weeks
      postoperatively). All urethral calculi were removed in the nine dogs. No
      recurrence was found during the follow-up period. CLINICAL SIGNIFICANCE: A
      minimally invasive approach is used to treat urethral obstructions resulting from
      calculi in the male dogs.

PMID- 21906061
TI  - Hyaluronidase shortens levobupivacaine lumbosacral epidural anaesthesia in dogs.
AB  - OBJECTIVES: The aim of this study was to evaluate the effects of hyaluronidase
      added to levobupivacaine in lumbosacral epidural blockade in dogs. METHODS: Six
      adult mixed breed dogs (two males and four females) weighing 7 to 14 kg (10.5 +/
      1.5 kg) and aged two to five years were used. Each dog received both treatments
      in random order: levobupivacaine alone (LBA; n=6) or levobupivacaine plus
      hyaluronidase (LBH; n=6) administered in the lumbosacral epidural space. Systemic
      effects, spread and duration of anaesthesia and motor block were determined
      before treatment and at predetermined intervals. RESULTS: The duration of local
      anaesthesia was 90 +/-10 minutes (P=0.001) for LBH treatment and 150 +/-15
      minutes for LBA treatment. In the LBH treatment, anaesthesia reached the T12 to
      T13 dermatome and in the LBA treatment it reached the T11 to T12 dermatome in all
      animals in 5 and 15 minutes, respectively. Complete motor blockade was 75 +/-12
      minutes (P=0.01) and 120 +/-15 minutes for LBH and LBA treatments, respectively.
      CLINICAL SIGNIFICANCE: Hyaluronidase added to levobupivacaine significantly
      shortens the duration of epidural anaesthesia with the same dermatome spread into
      the epidural space in dogs.

PMID- 21906062
TI  - A retrospective study of the rate of postoperative septic arthritis following 353
      elective arthroscopies.
AB  - OBJECTIVE: To report the rate of postoperative septic arthritis following
      elective diagnostic and surgical arthroscopy in small animals within a clinical
      setting. METHODS: A retrospective case review from the case log of one veterinary
      surgeon. RESULTS: Of the 353 procedures included, performed on 305 animals, there
      were three cases of postoperative sepsis (0.85%). CLINICAL SIGNIFICANCE:
      Interventional arthroscopy including both diagnostic and surgical arthroscopy in
      small animals is a safe technique and poses a risk of postoperative sepsis of
      approximately 1%.

PMID- 21906063
TI  - Computed tomographic findings in canine pyothorax and correlation with findings
      at exploratory thoracotomy.
AB  - OBJECTIVES: To describe computed tomographic (CT) findings in canine spontaneous
      pyothorax and compare them to surgical findings and to assess the utility of CT
      in guiding case management. METHODS: Records from 2003 to 2010 were reviewed to
      identify dogs, with spontaneous pyothorax, which had undergone CT. Cases were
      managed medically or surgically. CT images and surgery reports were reviewed and
      compared for surgical cases. RESULTS: Twelve dogs were included. Eight were
      managed surgically, three were managed medically and one died before management.
      Pleural fluid was present in all dogs on CT (n=12) and at surgery (n=8). Pleural
      gas was identified in five dogs on CT. Pleural thickening was detected in eight
      dogs on CT (seven visceral, one parietal and six mediastinal) and eight dogs at
      surgery (seven visceral, eight parietal and six mediastinal), six of which were
      identified by CT. Abnormal pulmonary parenchyma was detected in 10 dogs on CT and
      5 dogs at surgery, all of which were identified by CT. Mediastinal involvement
      was detected in 10 dogs on CT and 6 dogs at surgery, 5 of which were identified
      by CT. CONCLUSIONS: CT and surgical findings are similar in most cases of canine
      spontaneous pyothorax. CT may be a useful diagnostic tool for guiding case
      management.

PMID- 21906064
TI  - Gammopathy in a Spanish dog infected with Bartonella henselae.
AB  - Generalised pyogranulomatous disease and hyperviscosity syndrome associated with
      a presumed monoclonal gammopathy was diagnosed in a three-year-old intact female
      Pomeranian. The Bartonella henselae antibody titer was 1:64 and Bartonella
      species DNA was amplified from the splenic tissue. Monoclonal gammopathies in
      dogs are typically associated with plasma cell and lymphoid dyscrasias and other
      inflammatory or infectious diseases such as ehrlichiosis and leishmaniosis. Based
      on this case report, infection with Bartonella species should also be added to
      the differential diagnoses for gammopathy in dogs. To the authors' knowledge,
      this is the first report of molecular evidence of Bartonella species infection in
      a sick dog in Spain.

PMID- 21906065
TI  - Patent ductus arteriosus in a family of Chihuahuas.
AB  - This report describes a patent ductus arteriosus (PDA) in four puppies from the
      same family of Chihuahuas, bred from the same mother and from two different
      litters. Identification of this congenital anomaly relies on clinical
      examination, radiography and ultrasonography. Three of these puppies were female,
      and had a type-1 PDA. A conventional surgical ligation was performed on one of
      them, whilst the others underwent no treatment. One puppy was male, and presented
      with a type-4 PDA, requiring euthanasia. Post-mortem examination and
      histopathological examination of the PDA allowed characterisation of the
      histological anomalies, which were identical to those described in other breeds.
      The mother and the two stud dogs were not affected. Even though the mode of
      transmission has not been fully identified, it is evident that this PDA is
      hereditary in nature. To the authors' knowledge this is the first description of
      this congenital cardiopathy in a family of this breed, and in a significant
      number of first-generation individuals.

PMID- 21906066
TI  - Use of strontium-90 plesiotherapy for the treatment of a lingual plasmacytoma in
      a dog.
AB  - A 12-year-old, 25 kg, intact male St Bernard crossbreed was presented for
      treatment of a 538 mm ulcerated tumour on the dorsal tongue. Fine-needle
      aspiration cytology revealed a plasmacytoma. The dog staged negative for evidence
      of local metastatic or systemic disease. Histopathology confirmed the diagnosis.
      Treatment with one 150 Gy dose of radiation delivered with strontium-90
      plesiotherapy was performed. Side effects were not noted and there was no visible
      evidence of tumour remaining at 2 months and 1 year after therapy.

PMID- 21906069
TI  - Non-enhancing confirmed oligodendroglioma in three dogs.

PMID- 21906070
TI  - Stem anatomy supports Arabidopsis thaliana as a model for insular woodiness.

PMID- 21906071
TI  - The relationship between performance-based self-esteem and self-reported work and
      health behaviors among Danish knowledge workers.
AB  - Since knowledge intensive work often requires self-management, one might fear
      that persons who are dependent on work success for self-esteem will have
      difficulties in finding a healthful and sustainable balance between internal
      needs and external demands. Accordingly, we examined to what degree work-related
      performance-based self-esteem (PBS) was linked to work and health behaviors in
      392 knowledge workers (226 women, 166 men). In the women group, multiple binary
      logistic regression analyses with repeated measurements showed that the PBS score
      was associated with 10 of the 17 examined work and health behaviors. For men the
      corresponding figure was 3 of 17. In both men and women, higher PBS scores were
      positively associated with reports of efforts and strivings for work as well as
      attending work while ill. In conclusion, statistically significant relationships
      between PBS and work and health behaviors were more clearly visible among women
      than men. Whether this gender difference is dependent on the study design, or on
      true inherent differences between women and men, cannot be concluded with any
      certainty. However, persons who described themselves as being relatively more
      dependent on work accomplishments for a high self-esteem, as expressed by the PBS
      score, seem to display work behaviors that may lessen their restitution time. In
      addition, they also seem to be more prone to work while sick.

PMID- 21906072
TI  - Airborne contact dermatitis to triclosan.

PMID- 21906073
TI  - Ascaridole, a sensitizing component of tea tree oil, patch tested at 1% and 5% in
      two series of patients.

PMID- 21906074
TI  - Occupational allergic contact dermatitis of the ears caused by thiurams in a
      headset.

PMID- 21906075
TI  - Facial leucoderma following eczema: a new case induced by spectacle frames.

PMID- 21906076
TI  - Allergic contact dermatitis caused by chromium in a mobile phone.

PMID- 21906077
TI  - A case of occupational allergic contact dermatitis in a plumber performing
      pipeline repair.

PMID- 21906078
TI  - Mast cells are critically involved in serum-mediated vascular leakage in chronic
      urticaria beyond high-affinity IgE receptor stimulation.
AB  - BACKGROUND: Chronic urticaria (CU) is one of the most common skin disorders whose
      pathogenic mechanisms are not fully clarified. Autoimmune aetiology can be
      ascribed to 45% of patients with CU, and basophil histamine release is positive
      in 40% of cases. Our aim was to use a novel approach to evaluate the serum
      permeabilizing effect to identify the mediators of endothelial cell (EC) leakage
      and to define the role of mast cells (MCs) in the process. METHODS:
      Permeabilizing activity of sera from 19 patients with CU and 11 healthy blood
      donors was evaluated by measuring serum-induced degranulation of two MC lines,
      expressing (LAD2) or lacking (HMC-1) the IgE receptor. Mast cell supernatant (SN)
      was then incubated with an EC monolayer, and endothelial permeability was
      evaluated by Fluorescein isothiocyanate-bovine serum albumin leakage in a
      transwell system. RESULTS: All 19 patient sera failed to induce direct EC
      leakage, but 15/19 and 17/19 promoted degranulation of HMC-1 and LAD2,
      respectively. Interestingly, 85% of autologous serum skin test-negative sera were
      able to cause MC degranulation. Also, 17/19 SNs from HMC-1 and all SNs from LAD2
      incubated with CU sera increased endothelial permeability. Endothelial cell
      leakage remained unchanged after Ig depletion and was prevented by antihistamine,
      platelet-activating factor or leukotriene antagonist. CONCLUSIONS: Our study
      shows that CU sera are able to degranulate MCs through an IgE- and IgG
      independent mechanism. The nature of histamine-releasing factors involved is
      still unclear, but our finding opens new ways to the understanding of the
      pathogenesis of CU, particularly in patients not showing circulating
      autoantibodies to FcepsilonRI or IgE.

PMID- 21906079
TI  - Macrophages from patients with atopic dermatitis show a reduced CXCL10 expression
      in response to staphylococcal alpha-toxin.
AB  - BACKGROUND:   Patients with atopic dermatitis (AD) are frequently colonized with
      Staphylococcus aureus (S. aureus), one-third of them producing alpha-toxin, which
      is correlated with the severity of eczema in AD. Staphylococcus aureus colonizes
      in patients with psoriasis as well. Distinct expression of chemokine (C-C motif)
      ligand (CCL) and chemokine (C-X-C motif) ligand (CXCL) chemokines has been
      documented in both diseases. In this study, we investigated the effects of
      sublytic alpha-toxin concentrations on human macrophages that accumulate in the
      skin of patients with AD and psoriasis. METHODS:   IFN-gamma-induced protein of
      10-kDa (IP-10)/CXCL10 and macrophage-derived chemokine (MDC)/CCL22 production
      were evaluated at the mRNA or at the protein level using qRT-PCR or ELISA,
      respectively. Cell surface markers' expression and chemotaxis were determined by
      flow cytometry and Boyden chamber technique, respectively. RESULTS:   Sublytic
      concentrations of alpha-toxin strongly induced CXCL10 in macrophages at both the
      mRNA and the protein levels and significantly up-regulated MHC class II
      expression. Supernatants of alpha-toxin-stimulated macrophages induced the
      migration of human CD4+ lymphocytes via the CXCL10 receptor (CXCR3). Macrophages
      from patients with AD produced lower levels of CXCL10 compared to cells from
      patients with psoriasis as well as healthy controls in response to alpha-toxin.
      alpha-Toxin did not lead to a large variation in CCL22 production in macrophages
      from all three groups. CONCLUSIONS:   Staphylococcal alpha-toxin contributes to
      Th1 polarization by induction of CXCL10 in macrophages. Macrophages from patients
      with AD and psoriasis responded to alpha-toxin in the induction of Th1-related
      chemokine CXCL10 diversely, which could favour the recruitment of distinct
      leucocyte subsets into the skin.

PMID- 21906080
TI  - A porcine lymphocyte model for P-gp inhibition studies.

PMID- 21906081
TI  - The correlation between epidermal lipid composition and morphologic skin
      characteristics with percutaneous permeation: an interspecies comparison of
      substances with different lipophilicity.

PMID- 21906082
TI  - Absorption-dependent apparent volume of distribution at steady state (V(ss)/F) in
      pharmacokinetic data analysis.

PMID- 21906083
TI  - Detection of ceftiofur and oxytetracycline in oral fluids of swine with a pen
      side competitive ELISA test after intramuscular injection.

PMID- 21906084
TI  - The pharmacokinetics of hydrochlorothiazide in the camel.

PMID- 21906085
TI  - Cytochrome P450 3A expression and function in liver and intestinal mucosa from
      dexamethasone-treated sheep.
AB  - The effects of repeated administrations of dexamethasone (DEX) (3 mg/kg/day by
      i.m. route for 7 days) on the gene expression profile of a cytochrome P450 (CYP)
      3A28-like isoenzyme, on the expression of a CYP3A-immunoreactive protein and on
      CYP3A-dependent metabolic activities in sheep liver and small intestinal mucosa
      were evaluated in the current work. CYP 3A-dependent metabolic activities
      (erythromycin and triacetyl-oleandomycin N-demethylations) were assessed in
      microsomal fractions. The mRNA expression of CYP3A28-like, glucocorticoid
      receptor, constitutive androstane receptor, pregnane X receptor and retinoic X
      receptor alpha (RXRalpha) was determined by quantitative real-time PCR. The
      expression of a CYP3A-immunoreactive protein was measured by Western blot
      analyses. In the liver, DEX treatment increased CYP3A28-like mRNA levels (2.67
      fold, P<0.01) and CYP3A apoprotein expression (1.34-fold, P<0.05) and stimulated
      CYP3A-dependent metabolism. High and significant correlation coefficients between
      CYP3A-dependent activities and CYP3A28-like gene (r=0.835-0.856, P<0.01) or
      protein (r=0.728-0.855, P<0.05) expression profiles were observed. Among the
      transcriptional factors, DEX only stimulated (2.1-fold, P<0.01) the mRNA
      expression of RXRalpha. In sheep small intestine, DEX caused a slight increment
      (34.6%, P<0.05) in erythromycin N-demethylase activity in the jejunal mucosa and
      a significant enhancement (P<0.05) of CYP3A apoprotein level in the duodenal
      mucosa.

PMID- 21906086
TI  - A comparison of two gutta-percha master points consisting of different phases in
      filling of artificial lateral canals and depressions in the apical region of root
      canals when using a warm vertical compaction technique.
AB  - AIM: Two types of gutta-percha master points consisting of different phases of
      the material were compared during the filling of lateral canals and depressions
      in the apical region of root canals when using warm vertical compaction (WVC).
      METHODOLOGY: Two split-tooth models were constructed one with lateral canals 1, 2
      and 3 mm from the working length (WL) and another with depressions 1 and 3 mm
      from the WL. For each model, canal filling was performed with either alpha-phase
      or beta-phase gutta-percha. The gutta-percha was condensed with a System B
      plugger placed 7, 5 or 3 mm from the WL. The mean depth of gutta-percha
      penetration into the lateral canals and the percentage of depression area covered
      by gutta-percha were measured. A two-factor analysis of variance and a Student
      Newman-Keuls test (P < 0.05) were used to compare the two gutta-percha and three
      plugger insertion depths. RESULTS: At the 1-2 mm apical levels, alpha-phase gutta
      percha and deeper plugger depth elicited better flow into canals and depressions
      (P < 0.01). At the 3 mm apical level, the alpha-phase and beta-phase gutta-percha
      penetrated to the same extent with 3- and 5-mm plugger insertions (P > 0.05);
      however, with the 7-mm plugger insertion, the alpha-phase gutta-percha flowed
      significantly more deeply than the beta-phase gutta-percha (P < 0.01). At the 2-3
      mm apical levels, the 3 and 5 mm plugger depths elicited similar flow (P > 0.05);
      both elicited significantly better flow than the 7 mm plugger depth (P < 0.01).
      CONCLUSION: The alpha-phase gutta-percha with deep plugger insertion during warm
      vertical compaction using a System B heat source moved singificantly more into
      lateral canals and depressions than the beta-phase gutta-percha.

PMID- 21906087
TI  - Retrospective long-term evaluation of autotransplantation of premolars to the
      central incisor region.
AB  - AIM:   This retrospective case-series study aimed to examine the long-term
      outcomes of autogenously transplanted premolars. METHODOLOGY:   Twelve patients
      in whom donor premolars were used to replace maxillary central incisors lost by
      trauma were clinically and radiologically monitored. Standardized clinical and
      radiographic records were systematically obtained during the follow-up period of
      14 years, to determine the influence of specific clinical criteria on the overall
      success rate of transplantation. RESULTS:   The success rate of premolar
      autotransplantation in the maxillary central incisor area was 80% after 14 years
      follow-up. The highest success rate occurred in those teeth transplanted with two
      thirds of full root development. Complete pulp obliteration was positively
      related to autotransplant viability, followed by root formation in the bony
      crypt. CONCLUSIONS:   Autotransplantation of donor teeth, at the stage of 1/2 to
      3/4 of their expected root length, can provide a successful treatment solution
      for over 14 years.

PMID- 21906088
TI  - Comparison of the surface tension of 5.25% sodium hypochlorite solution with
      three new sodium hypochlorite-based endodontic irrigants.
AB  - AIM: To investigate the surface tension characteristics of 5.25% sodium
      hypochlorite and three recently introduced sodium hypochlorite solutions, which
      had been modified to reduce their surface tension: Chlor-Xtra, Hypoclean A and
      Hypoclean B. METHODOLOGY: Freshly produced MilliQ water was used as a reference
      liquid. All measurements of surface tension were taken by the Wilhelmy plate
      technique, using a Cahn DCA-322 Dynamic Contact Angle Analyzer at the temperature
      of 22  degrees C. A glow-discharge cleaned glass slide was immersed in 5 mL of
      the test liquid in a beaker cleaned with hot chromic acid, rinsed with MilliQ
      water and finally air plasma-cleaned in a glow-discharge reactor. The force on
      the glass slide was recorded continuously by the instrument software as the
      beaker was raised and withdrawn at the constant speed of 40 micron/s, until at
      least 1 cm of the glass slide was immersed. The typical accuracy was 0.5 mJ m(
      2). For each sample, fifteen measurements were taken, and mean values were
      calculated. A Kruskal-Wallis anova analysis, followed by Mann-Whitney's U rank
      sum test for pair-wise comparisons, was used to compare surface tension values.
      Statistical significance was set at alpha = 0.05. RESULTS: MilliQ water (72.13 mJ
      m(-2)) and 5.25% sodium hypochlorite (48.90 mJ m(-2) ) had the highest surface
      tension values (P < 0.01) compared to Chlor-Xtra (33.14 mJ m(-2)), Hypoclean B
      (30.00 mJ m(-2) ) and Hypoclean A (29.13 mJ m(-2)). Hypoclean A had the lowest
      surface tension (P < 0.01). CONCLUSIONS: The new 5.25% sodium hypochlorite
      solutions modified with surfactants, Hypoclean A and Hypoclean B, had surface
      tension values that were significantly lower (P < 0.01) than Chlor-Xtra and 5.25%
      NaOCl. Because of their low surface tension and increased contact with dentinal
      walls, these new irrigants have the potential to penetrate more readily into
      uninstrumented areas of root canal system as well as allow a more rapid exchange
      with fresh solution, enabling greater antimicrobial effectiveness and enhanced
      pulp tissue dissolution ability.

PMID- 21906090
TI  - The easy success of the Spanish model for organ transplantation.

PMID- 21906091
TI  - Welcome to the European Society for Artificial Organs-International Federation
      for Artificial Organs joint congress in Porto, Portugal.

PMID- 21906092
TI  - Welcome to the 4th joint European Society for Artificial Organs-international
      Federation for Artificial Organs Congress.

PMID- 21906093
TI  - Left ventricular temporary assistance: by blood propelling or counterpulsating?

PMID- 21906094
TI  - Effect of dobutamine combined with intra-aortic balloon counterpulsation on left
      ventricular function early after acute myocardial infarction: experimental study.
AB  - Acute myocardial infarction (AMI) causes left ventricular (LV) remodeling, which
      forms the substrate for its early and late complications. The purpose of this
      study was to compare the acute effect of dobutamine or intra-aortic balloon
      pumping (IABP), alone or in combination, on LV function in the early phase of an
      experimental AMI. In 18 pigs, AMI was induced by ligation of the left anterior
      descending artery (LAD). IABP or dobutamine infusion at a rate of 5 ug/kg/min, or
      a combination of the two, was applied immediately after ligation of the LAD.
      Echocardiographic measurements of the long and short LV axes were obtained before
      (baseline) and post LAD ligation and at the end of each intervention for 5, 15,
      and 30 min. The fractional shortening (FS) of both axes, as well as the ejection
      fraction (EF), was calculated. The combination of dobutamine with IABP increased
      the EF significantly after the AMI in comparison to dobutamine or IABP alone, and
      improved the stroke volume, cardiac output, and long axis FS in comparison to
      IABP alone. Dobutamine alone produced a significantly higher increase of EF in
      comparison to IABP alone. These results indicate that the combination of
      dobutamine with IABP may be useful during AMI.

PMID- 21906096
TI  - Radiographic quantitative assessment of caudal proximal tibial angulation in 100
      dogs with cranial cruciate ligament rupture.
AB  - OBJECTIVE: To evaluate inter- and intraobserver variability in the measurement of
      distal tibial axis/proximal tibial axis angle (DPA) from lateral radiographs of
      canine tibia in dogs with cranial cruciate ligament rupture (CCLR). STUDY DESIGN:
      Retrospective clinical study. ANIMALS: Dogs (n=100) with cranial cruciate
      ligament rupture. METHODS: Medical records of dogs diagnosed with CCLR were
      reviewed. In addition to signalment and TPA measurements, measured DPA (mDPA) was
      calculated for each lateral view of the tibia in each animal, twice, by 3 blinded
      observers. Subjective scoring of DPA (sDPA) was also recorded, twice, by 3
      additional blinded observers from lateral views of the proximal half of the tibia
      in each dog. Inter- and intraobserver variability was measured by intraclass
      correlation coefficient (ICC) for each measurement. Correlation between mDPA and
      sDPA was also determined. RESULTS: Median tibial plateau angle (TPA) of the
      subject population was 27.9 degrees  (range 18.8-41.3 degrees ; IQR: 25.5-30.75
      degrees ). Mean +/- SD mDPA was 6.50 +/- 2.81 degrees  (confidence intervals
      [CI]: 5.94-7.06 degrees ; range 0-13.33 degrees ). There was no correlation
      between age and weight of dogs and the mDPA (P=.58 and .12). There was a moderate
      correlation between mDPA and TPA (r(2)=0.49, P<.0001). There was a moderate
      correlation between sDPA and mDPA (r(2)=0.27, P<.0001). Good inter- and
      intraobserver agreement was found in the measurement of mDPA. CONCLUSION: mDPA is
      a reproducible measurement of caudal angulation of proximal tibia. Furthermore,
      mDPA of dogs with cranial cruciate ligament disease in this report are in
      concordance with previous reports.

PMID- 21906097
TI  - Quantitative trait loci for clinical mastitis on chromosomes 2, 6, 14 and 20 in
      Norwegian Red cattle.
AB  - Mastitis is the most frequent and costly disease in dairy production and
      solutions leading to a reduction in the incidence of mastitis are highly
      demanded. Here a genome-wide association study was performed to identify
      polymorphisms affecting susceptibility to mastitis. Genotypes for 17 349 SNPs
      distributed across the 29 bovine autosomal chromosomes from a total of 2589 sires
      with 1 389 776 daughters with records on clinical mastitis were included in the
      analysis. Records of occurrence of clinical mastitis were divided into seven time
      periods in the first three lactations in order to identify quantitative trait
      loci affecting mastitis susceptibility in particular phases of lactation. The
      most convincing results from the association mapping were followed up and
      validated by a combined linkage disequilibrium and linkage analysis. The study
      revealed quantitative trait loci affecting occurrence of clinical mastitis in the
      periparturient period on chromosomes 2, 6 and 20 and a quantitative trait locus
      affecting occurrence of clinical mastitis in late lactation on chromosome 14.
      None of the quantitative trait loci for clinical mastitis detected in the study
      seemed to affect lactation average of somatic cell score. The SNPs highly
      associated with clinical mastitis lie near both the gene encoding interleukin 8
      on chromosome 6 and the genes encoding the two interleukin 8 receptors on
      chromosome 2.

PMID- 21906098
TI  - Genome-wide association mapping in Norwegian Red cattle identifies quantitative
      trait loci for fertility and milk production on BTA12.
AB  - Reproductive performance is a critical trait in dairy cattle. Poor reproductive
      performance leads to prolonged calving intervals, higher culling rates and extra
      expenses related to multiple inseminations, veterinary treatments and
      replacements. Genetic gain for improved reproduction through traditional
      selection is often slow because of low heritability and negative correlations
      with production traits. Detection of DNA markers associated with improved
      reproductive performance through genome-wide association studies could lead to
      genetic gain that is more balanced between fertility and production. Norwegian
      Red cattle are well suited for such studies, as very large numbers of detailed
      reproduction records are available. We conducted a genome-wide association study
      for non-return rate, fertility treatments and retained placenta using almost 1
      million records on these traits and 17 343 genome-wide single-nucleotide
      polymorphisms. Genotyping costs were minimized by genotyping the sires of the
      cows recorded and by using daughter averages as phenotypes. The genotyped sires
      were assigned to either a discovery or a validation population. Associations were
      only considered to be validated if they were significant in both groups. Strong
      associations were found and validated on chromosomes 1, 5, 8, 9, 11 and 12.
      Several of these were highly supported by findings in other studies. The most
      important result was an association for non-return rate in heifers in a region of
      BTA12 where several associations for milk production traits have previously been
      found. Subsequent fine-mapping verified the presence of a quantitative trait loci
      (QTL) having opposing effects on non-return rate and milk production at 18 Mb.
      The other reproduction QTL did not have pleiotropic effects on milk production,
      and these are therefore of considerable interest for use in marker-assisted
      selection.

PMID- 21906099
TI  - Global gene expression profiling reveals genes expressed differentially in cattle
      with high and low residual feed intake.
AB  - Feed efficiency is an economically important trait in beef production. It can be
      measured as residual feed intake. This is the difference between actual feed
      intake recorded over a test period and the expected feed intake of an animal
      based on its size and growth rate. DNA-based marker-assisted selection would help
      beef breeders to accelerate genetic improvement for feed efficiency by reducing
      the generation interval and would obviate the high cost of measuring residual
      feed intake. Although numbers of quantitative trait loci and candidate genes have
      been identified with the advance of molecular genetics, our understanding of the
      physiological mechanisms and the nature of genes underlying residual feed intake
      is limited. The aim of the study was to use global gene expression profiling by
      microarray to identify genes that are differentially expressed in cattle, using
      lines genetically selected for low and high residual feed intake, and to uncover
      candidate genes for residual feed intake. A long-oligo microarray with 24 000
      probes was used to profile the liver transcriptome of 44 cattle selected for high
      or low residual feed intake. One hundred and sixty-one unique genes were
      identified as being differentially expressed between animals with high and low
      residual feed intake. These genes were involved in seven gene networks affecting
      cellular growth and proliferation, cellular assembly and organization, cell
      signalling, drug metabolism, protein synthesis, lipid metabolism, and
      carbohydrate metabolism. Analysis of functional data using a transcriptional
      approach allows a better understanding of the underlying biological processes
      involved in residual feed intake and also allows the identification of candidate
      genes for marker-assisted selection.

PMID- 21906100
TI  - Caecal transcriptome analysis of colonized and non-colonized chickens within two
      genetic lines that differ in caecal colonization by Campylobacter jejuni.
AB  - Campylobacter jejuni is one of the most common causes of human bacterial
      enteritis worldwide. The molecular mechanisms of the host responses of chickens
      to C. jejuni colonization are not well understood. We have previously found
      differences in C. jejuni colonization at 7-days post-inoculation (pi) between two
      genetic broiler lines. However, within each line, not all birds were colonized by
      C. jejuni (27.5% colonized in line A, and 70% in line B). Therefore, the
      objective of the present experiments was to further define the differences in
      host gene expression between colonized and non-colonized chickens within each
      genetic line. RNA isolated from ceca of colonized and non-colonized birds within
      each line was applied to a chicken 44K Agilent microarray for the pair
      comparison. There were differences in the mechanisms of host resistant to C.
      jejuni colonization between line A and line B. Ten times more differentially
      expressed genes were observed between colonized and non-colonized chickens within
      line B than those within line A. Our study supports the fact that the MAPK
      pathway is important in host response to C. jejuni colonization in line B, but
      not in line A. The data indicate that inhibition of small GTPase-mediated signal
      transduction could enhance the resistance of chickens to C. jejuni colonization
      and that the tumour necrosis factor receptor superfamily genes play important
      roles in determining C. jejuni non-colonization in broilers.

PMID- 21906101
TI  - Muscle transcriptome profiling in divergent phenotype swine breeds during growth
      using microarray and RT-PCR tools.
AB  - Using an array consisting of 10 665 70-mer oligonucleotide probes, the
      longissimus dorsi muscle tissue expression during growth in nine pigs belonging
      to Casertana (CT), an autochthonous breed characterized by slow growth and a
      massive accumulation of backfat, was compared with that of two cosmopolitan
      breeds, Large White (LW) and a crossbreed (CB; Duroc * Landrace * Large White).
      The results were validated by real-time PCR. All animals were of the same age and
      were raised under the same environmental conditions. Muscle tissues were
      collected at 3, 6, 9 and 11 months of age, and a total of 173 genes showed
      significant differential expression between CT and the cosmopolitan genetic types
      at 3 months of age. Time series cluster analysis indicated that the CT breed had
      a different pattern of gene expression compared with that of the LW and the CB.
      Four of the eight clusters highlighted the gene differences between CT and the
      other two breeds, which were further supported by statistical analyses: clusters
      4 and 5 contained a total of 71 genes that were underexpressed at 3 months of
      age, and cluster 3 and cluster 7 included 28 and 42 genes respectively that were
      overexpressed at 3 months of age. As expected, differentially expressed genes
      belonged to the category of genes coding for contractile fibres and transcription
      factors involved in muscle development and differentiation. These findings
      highlight muscle expression genes during pig growth and are useful to understand
      the genetic meaning of the different developmental rates.

PMID- 21906102
TI  - Transcription specificity of the class Ib genes SLA-6, SLA-7 and SLA-8 of the
      swine major histocompatibility complex and comparison with class Ia genes.
AB  - Our aim was to analyse the transcription levels of the three non-classical class
      Ib genes SLA-6, SLA-7 and SLA-8 of the swine major histocompatibility complex in
      various tissues and conditions and to compare them to the transcription levels of
      classical class Ia genes. Twenty-five adult tissues from two pig breeds, pig
      renal PK15 cells infected with the Pseudorabies virus, and peripheral blood
      mononuclear cells (PBMCs) stimulated by lipopolysaccharide or a mixture of
      phorbol myristate acetate and ionomycin were included in our study. Relative
      transcription was quantified by quantitative real-time PCR. On average, in adult
      tissues and PBMCs and compared to SLA-6, the transcription level of SLA-Ia genes
      was 100-1000 times higher, the level of SLA-8 was 10-20 times higher, and that of
      SLA-7 was five times higher. Thus, SLA-8 is the most transcribed SLA-Ib gene,
      followed by the SLA-7 and SLA-6 genes. The highest transcription levels of SLA-Ib
      transcripts were found in the lymphoid organs, followed by the lung and the
      digestive tract. The tissue variability of expression levels was widest for the
      SLA-6 gene, with a 1:32 ratio between the lowest and highest levels in contrast
      to a 1:12 ratio for the SLA-7 and SLA-8 genes and a 1:16 ratio for the SLA-Ia
      genes. During PK-15 infection and PBMC stimulation, SLA-Ia and SLA-8 genes were
      downregulated, whereas SLA-6 and SLA-7 were upregulated, downregulated or not
      significantly modified. Our overall results confirm the tissue-wide transcription
      of the three SLA-Ib genes and suggest that they have complementary roles.

PMID- 21906103
TI  - Integrating comparative expression profiling data and association of SNPs with
      Salmonella shedding for improved food safety and porcine disease resistance.
AB  - Salmonella in swine is a major food safety problem, as the majority of US swine
      herds are Salmonella-positive. Salmonella can be shed from colonized swine and
      contaminate (i) neighbouring pigs; (ii) slaughter plants and pork products; (iii)
      edible crops when swine manure is used as a fertilizer; and (iv) water supplies
      if manure used as crop fertilizer runs off into streams and waterways. A
      potentially powerful method of addressing pre-harvest food safety at the farm
      level is through genetic improvement of disease resistance in animals. In this
      research, we describe a successful strategy for discovering genetic variation at
      candidate genes associated with disease resistance in pigs. This involves
      integrating our recent global gene expression analysis of the porcine response to
      Salmonella with information from the literature about important candidate genes.
      We identified single-nucleotide polymorphisms (SNPs) in these functional
      candidate genes and genotyped three independent pig populations that had data on
      Salmonella faecal shedding or internal burden (total n = 377) at these loci. Of
      31 SNPs genotyped, 21 SNPs segregated in at least two populations with a minor
      allele frequency of 15% or greater. Statistical analysis revealed thirteen SNPs
      associated with Salmonella faecal shedding or tissue colonization, with an
      estimated proportion of false positives (PFP) <=0.2. The genes with associated
      SNPs included GNG3, NCF2, TAP1, VCL, AMT, CCR1, CD163, CCT7, EMP1 and ACP2. These
      associations provide new information about the mechanisms of porcine host
      response to Salmonella and may be useful in improving genetic resistance to this
      bacterium.

PMID- 21906104
TI  - Novel polymorphisms in ovine immune response genes and their association with
      abortion.
AB  - The sheep has worldwide agricultural importance, yet the genetic control of the
      immune responses underlying susceptibility or resistance to ovine disease is
      little understood. Here, we identify six novel polymorphisms in the ovine immune
      response genes interferon-gamma (IFNG), tumour necrosis factor-alpha (TNF),
      interleukin-1beta (IL1B) and interleukin-4 (IL4) in pedigree Charollais flocks.
      We confirm the presence of previously reported polymorphisms in IFNG and IL1B in
      Charollais. Restriction fragment length polymorphism (RFLP) genotyping assays
      have been developed for four polymorphisms, IFNGg.168C>T, IFNGg.285A>G,
      IL1Bg.689C>T and TNFg.3UTRA>G, and a Taqman genotyping assay has been developed
      for IL4g.485C>T. The previously described IL2g.647C>T polymorphism is adapted for
      RFLP analysis. Allele frequencies are described in Charollais, Lleyn and Suffolk
      cross sheep. Polymorphisms are typed in both Charollais ewes and lambs and
      analysed against abortion phenotypes. A subset of animals have also been analysed
      for the presence of Toxoplasma gondii, an abortion-causing protozoan. The
      IFNGg.168T allele is shown to be associated with increased risk of a ewe having
      an abortion, while the IFNGg.285G allele is associated with increased risk of a
      lamb being aborted. These assays provide tools for the investigation of the
      genetic basis of other phenotypes in sheep, including infectious disease
      susceptibility.

PMID- 21906105
TI  - SNP-based association mapping of Arachnomelia in Fleckvieh cattle.
AB  - Bovine arachnomelia is an inherited congenital disorder with malformation mainly
      of the limbs, the vertebral column and the skull, following a monogenic autosomal
      recessive heredity. Despite almost identical pathological findings, arachnomelia
      has previously been mapped to bovine chromosome 23 and 5 in Fleckvieh and
      Braunvieh respectively. Therefore, this disorder may be an example of locus
      heterogeneity in cattle. This study aimed to refine the candidate region to allow
      positional cloning and sequence analyses of candidate genes in Fleckvieh cattle.
      For that purpose, a case-control association mapping design was set up with a
      case group of 16 pre-selected affected individuals and a control group of 50
      unrelated animals. The subset of affected animals was selected from a total of
      129 pathologically confirmed cases due to the occurrence of recombination(s)
      within a 14.5 cM candidate interval previously mapped to chromosome 23. Six
      linked microsatellites currently used for indirect gene testing in Fleckvieh were
      analysed for this purpose. In all selected cases, a genome-wide scan using 44 473
      informative SNPs revealed shared segments of homozygosity at 15 adjacent SNPs on
      chromosome 23. Additional haplotype analysis of 37 carrier bulls confirmed the
      localization of the arachnomelia locus to a region of 927 kb (13.622-14.549 Mb)
      containing molybdenum cofactor biosynthesis protein 1 gene, the most likely
      candidate gene for arachnomelia in Fleckvieh. The number of recombinant
      haplotypes observed in cases was more than doubled compared with the number of
      expected recombinations. This remarkably increased mapping resolution and thus
      illustrates the benefit of pre-selection in association studies.

PMID- 21906106
TI  - Quantitative trait loci for fatness at growing and reproductive stages in Iberian
      * Meishan F(2) sows.
AB  - A considerable number of fatness QTL have been identified in growing pigs, but
      there is a lack of knowledge about the genetic architecture of this trait in
      gilts and sows. We have performed a genome scan, in 255 Iberian * Meishan F(2)
      sows, for backfat thickness (BF) at 150 (BF(150) ) and 210 (BF(210)) days of age,
      30 days after conception (BF(30)) and 7-10 days before farrowing (BF(bf)). We
      have found one BF150 QTL in SSC6 (120 cM) that was highly significant (P < 0.001)
      at the chromosome-wide level and suggestive at the genome-wide level (P < 0.1).
      Ten additional chromosome-wide significant QTL were found for sow BF(150) (SSC1,
      SSC13), BF(210) (SSC6, SSC8, SSC15), BF(30) (SSC5, SSC6) and BF(bf) (SSC1, SSC6,
      SSC13). The location of several of the BF QTL varied depending on the growing and
      reproductive status of the sow, suggesting that part of these genetic effects may
      have a temporal pattern of phenotypic expression.

PMID- 21906107
TI  - Refined mapping of the Escherichia coli F4ab/F4ac receptor gene(s) on pig
      chromosome 13.
AB  - Enterotoxigenic Escherichia coli expressing F4 fimbriae is the major cause of
      diarrhoea in neonatal and post-weaning piglets. Previous studies have revealed
      that the loci controlling the F4ab/F4ac receptors are located on SSC13q41,
      between markers SW207 and S0283. In this study, we refined their positions in a
      two generation population containing 366 piglets of three breeds (Large White,
      Landrace, and Songliao Black). Nine microsatellite markers within this region
      were selected from the MARC (U.S. Meat Animal Research Center) porcine linkage
      map, and the pedigree disequilibrium test was employed for fine-mapping. The
      F4abR gene was located in the interval between S0283 and SW1833, a 4.8-cM region,
      and the F4acR gene was located in the interval between S0283 and SW1876, a 1.6-cM
      region. Our results also suggest that the F4ab/F4ac receptors might be controlled
      by two different but closely linked loci. The results of microsatellite-based
      haplotype analysis in the corresponding region show that some specific haplotypes
      were overwhelmingly present in the adhesive or non-adhesive animals, indicating
      that there are mutations within the identified regions that are strongly
      associated with the F4ab/ac phenotypes.

PMID- 21906108
TI  - Sequence variants in the bovine nucleophosmin 1 gene, their linkage and their
      associations with body weight in native cattle breeds in China.
AB  - The nucleophosmin (nucleolar phosphoprotein B23, numatrin) gene (NPM1, previously
      known as nucleophosmin/nucleoplasmin family, member 1) encodes a multifunctional
      nucleolar phosphoprotein that plays a crucial role in cell growth and
      homeostasis. Seven sequence variants (SVs) were identified in the coding region
      of bovine NPM1, five of which were in complete linkage disequilibrium. Eight
      different haplotypes were identified, of which two major haplotypes have a
      frequency of 23.2% and 20.4%. Three SVs were significantly associated with body
      weight in the Nanyang population as analysed at different ages. No significant
      association was detected between 18 combined genotypes and body weight at five
      different ages. Our results suggest that some polymorphisms in NPM1 are
      associated with body weight at some ages and may be used as candidates for marker
      assisted selection and management in beef cattle breeding programmes.

PMID- 21906109
TI  - Genotypechecker: an interactive tool for checking the inheritance consistency of
      genotyped pedigrees.
AB  - Datapoint errors in pedigree genotype data sets are difficult to identify and
      adversely affect downstream genetic analyses. We present GenotypeChecker, a
      desktop software tool for assisting data cleansing. The application identifies
      likely data errors in pedigree/genotype data sets by performing an inheritance
      checking algorithm for each marker across the pedigree, and highlights
      inconsistently inherited genotypes in an exploratory user interface. By 'masking'
      suspect datapoints and rechecking inheritance consistency, erroneous datapoints
      can be confirmed and cleansed from the data set. The software, examples and
      documentation are freely available at
      http://bioinformatics.roslin.ac.uk/genotypechecker.

PMID- 21906110
TI  - Tracing genetic differentiation of Chinese Mongolian sheep using microsatellites.
AB  - The genetic consequences of population differentiation and isolation have been
      the subject of conservation biology. In this study, we analysed the genetic
      diversity and structure of Mongolian sheep in China. These animals belong to a
      traditional local breed with high production, extensive adaption, early maturity
      and roughage resistance. For this purpose, 26 microsatellites were genotyped for
      five Mongolian sheep populations. The Bayesian clustering indicated five clusters
      as the most probable genetic structure of the populations investigated. In
      addition, a clear genetic structure was revealed in three populations distributed
      at large geographical scales, while the other cluster encompassed UQ and HLBR
      sheep that displayed no clear differentiation, probably due to their close and
      small geographical distributions. Overall, our results are helpful in
      understanding the interplay of population dynamics in these close genetic
      lineages of Mongolian sheep.

PMID- 21906111
TI  - Genetic structure of the bovine Y-specific microsatellite UMN0103 reflects the
      genetic history of the species.

PMID- 21906112
TI  - Mapping of the Toll-like receptor family in channel catfish, Ictalurus punctatus.

PMID- 21906113
TI  - NAP1L5 is imprinted in porcine placenta.

PMID- 21906114
TI  - A gradient Markov chain Monte Carlo algorithm for computing multivariate maximum
      likelihood estimates and posterior distributions: mixture dose-response
      assessment.
AB  - Multivariate probability distributions, such as may be used for mixture dose
      response assessment, are typically highly parameterized and difficult to fit to
      available data. However, such distributions may be useful in analyzing the large
      electronic data sets becoming available, such as dose-response biomarker and
      genetic information. In this article, a new two-stage computational approach is
      introduced for estimating multivariate distributions and addressing parameter
      uncertainty. The proposed first stage comprises a gradient Markov chain Monte
      Carlo (GMCMC) technique to find Bayesian posterior mode estimates (PMEs) of
      parameters, equivalent to maximum likelihood estimates (MLEs) in the absence of
      subjective information. In the second stage, these estimates are used to
      initialize a Markov chain Monte Carlo (MCMC) simulation, replacing the
      conventional burn-in period to allow convergent simulation of the full joint
      Bayesian posterior distribution and the corresponding unconditional multivariate
      distribution (not conditional on uncertain parameter values). When the
      distribution of parameter uncertainty is such a Bayesian posterior, the
      unconditional distribution is termed predictive. The method is demonstrated by
      finding conditional and unconditional versions of the recently proposed emergent
      dose-response function (DRF). Results are shown for the five-parameter common
      mode and seven-parameter dissimilar-mode models, based on published data for
      eight benzene-toluene dose pairs. The common mode conditional DRF is obtained
      with a 21-fold reduction in data requirement versus MCMC. Example common-mode
      unconditional DRFs are then found using synthetic data, showing a 71% reduction
      in required data. The approach is further demonstrated for a PCB 126-PCB 153
      mixture. Applicability is analyzed and discussed. Matlab((r))  computer programs
      are provided.

PMID- 21906115
TI  - Four polymorphisms of the CAPN 10 gene and their relationship to polycystic ovary
      syndrome susceptibility: a meta-analysis.
AB  - OBJECTIVE:   To investigate the association between CAPN 10 gene polymorphism and
      polycystic ovary syndrome (PCOS) susceptibility. DESIGN: Meta-analysis of
      published case-control studies of four single nucleotide polymorphisms (SNPs) in
      CAPN 10 and PCOS susceptibility. PATIENTS:   Women with PCOS. MEASUREMENTS:  
      Odds ratios (ORs) and 95% confidence intervals (CIs) for heterozygous,
      homozygous, dominant model, recessive model and allele. RESULTS:   A total of 11
      studies were involved in the meta-analysis. UCSNP-63 was significantly associated
      with PCOS, with homozygous carriers (TT vs CC: OR = 0.64; 95% CI: 0.45-0.90) and
      recessive model (TT vs CC and CT: OR = 0.64; 95% CI: 0.45-0.90) being protective
      factors. In addition, UCSNP-19 was significantly associated with PCOS, with
      recessive model (ins/ins vs del/del and del/ins: OR = 0.72, 95% CI: 0.59-0.88)
      and insert allele (ins vs del: OR = 0.85, 95% CI: 0.76-0.96) being protective
      factors, while heterozygous carriers (del/ins vs del/del: OR = 1.56, 95% CI: 1.24
      1.94) and deletion allele (del vs ins: OR = 1.18, 95% CI: 1.04-1.32) being risk
      factors. However, no significant associations were found between UCSNP-44, -43
      and PCOS. Moreover, the results of the Rotterdam criteria subgroup analysis were
      similar with that of overall analysis. CONCLUSIONS:   This is the first report on
      the association between CAPN 10 UCSNP-63 and PCOS in genotype, with homozygous
      carriers and recessive model being protective factors. Additionally, insert
      allele and recessive model of UCSNP-19 are protective factors, while deletion
      allele and heterozygous genotype are risk factors for PCOS development.

PMID- 21906116
TI  - Increased vitamin D supplementation recommended during summer season in the gulf
      region: a counterintuitive seasonal effect in vitamin D levels in adult,
      overweight and obese Middle Eastern residents.
AB  - PURPOSE:   Seasonal variations in circulating vitamin D levels provide vital
      information as to the most appropriate time to either start or increase vitamin D
      supplementation to maintain optimal vitamin D levels. In this follow-up study, we
      determined seasonal differences in serum 25(OH)-vitamin D (25(OH)D) levels, as
      well as parallel changes in metabolic parameters, in a cohort of adult,
      overweight and obese Saudis. METHODS:   A total of 121 adult, overweight, obese,
      and consenting Saudis aged 18-70 years were randomly recruited from four Primary
      Health Care Centers in Riyadh, Saudi Arabia. They were divided according to the
      season when baseline measurements were made [74 summer (April-October); 47 winter
      (November-March)]. Anthropometrics were obtained, and fasting blood samples were
      taken at baseline and every 3 months for 1 year. Fasting blood glucose, corrected
      calcium levels, and lipid profiles were measured routinely. Serum 25(OH)-vitamin
      D was quantified using a specific enzyme-linked immunosorbent assay (ELISA).
      RESULTS:   Age- and BMI-matched mean 25(OH)-vitamin D levels from the winter
      group were significantly higher than those of the summer group (P < 0.001). In
      both groups, HDL-C levels improved significantly as 25(OH)-vitamin D levels
      increased with subsequent follow-ups, even after adjusting for age, gender and
      BMI (P < 0.001). CONCLUSION:   Seasonal differences in serum 25(OH)-vitamin D
      levels in Saudi Arabia are counterintuitive, with circulating levels being higher
      during the winter than the summer season. Increased vitamin D supplementation is
      thus recommended to maintain optimal serum 25(OH)-vitamin D levels during the
      summer season.

PMID- 21906117
TI  - Endosteal bone storage in young adults born small for gestational age - a study
      using peripheral quantitative computed tomography.
AB  - OBJECTIVE: Poor growth early in life is associated with numerous adverse
      conditions including decreased bone mass. The aim is to investigate bone and body
      composition in young adults born small for gestational age (SGA). DESIGN:
      Observational study. PARTICIPANTS: A total of 76 young adults born SGA (34f) at a
      mean age of 19.68 +/- 0.5 years were enrolled. METHOD: Bone mineral density
      (BMD), bone geometry and body composition were analysed using peripheral
      quantitative computed tomography. RESULTS: Adults born SGA had significantly
      lower z-score for height (-0.86 +/- 0.87), weight (-0.61 +/- 0.78) and BMI (-0.38
      +/- 1.04) as well as fat cross-sectional area (CSA) (-0.62 +/- 0.80) compared
      with a healthy reference population (P < 0.05). Z-scores for trabecular and
      cortical BMD were normal. After correction for reduced height, z-scores for total
      CSA (-0.14 +/- 1.11) and muscle CSA (-0.21 +/- 0.99) were normal and medullary
      cavity (-0.71 +/- 0.80) was reduced. Those with a birthweight of <= 1500 g had
      even lower height-corrected z-scores for medullary cavity (-1.12 +/- 0.69) and
      total bone CSA (-0.58 +/- 0.93) (P < 0.05). After adjustment for sex and weight,
      significant partial correlations were detectable between BMI at the age of 48
      months and height-corrected z-scores for medullary cavity (r = 0.33, P = 0.020)
      and total CSA (r = 0.29, P = 0.04). CONCLUSION: Environmental factors early in
      life seem to influence bone geometry in adulthood. Young adults born SGA have
      normal total bone CSA but smaller medullary cavity. Those with very low
      birthweight, however, show compromised bone size development that may alter bone
      stability later in life.

PMID- 21906118
TI  - Diabetic peripheral neuropathy is highly associated with nontraumatic fractures
      in Korean patients with type 2 diabetes mellitus.
AB  - OBJECTIVE: Patients with type 2 diabetes mellitus are at greater risk of bone
      fractures than nondiabetics. However, the risk factors for fractures in patients
      with diabetes have not been fully evaluated. This study was designed to evaluate
      the relative frequency of fractures at different sites and the diabetes
      associated factors that affect nontraumatic bone fracture in patients with type 2
      diabetes. PATIENTS AND DESIGN: This retrospective case-control study recruited
      144 patients with type 2 diabetes, who presented with nontraumatic fractures
      between March 2004 and March 2009 and 150 age-, gender-, body mass index (BMI)-
      and duration of diabetes-matched control subjects. Nontraumatic fractures were
      confirmed using patients' medical records and radiological findings. All subjects
      were examined for their diabetes status and associated factors for fracture,
      including bone mineral density (BMD). RESULTS: Of 150 reported bone fractures,
      the hip was the most frequent fracture site (32.7%), followed by the upper
      extremity (19.3%). Nontraumatic fractures were associated with diabetic
      retinopathy, diabetic peripheral neuropathy, stroke history, previous fracture
      and insulin treatment (P < 0.05). In multivariate analyses, independently
      associated factors for bone fracture were diabetic peripheral neuropathy [odds
      ratio (OR) = 37.3, 95% confidence interval (CI) = 1.46-652.57] and previous
      fracture (OR = 9.54, 95% CI = 1.18-77.37; P < 0.05). CONCLUSIONS: The hip was the
      most frequent site of nontraumatic fracture, and diabetic peripheral neuropathy
      was significantly associated with an increased risk of nontraumatic fractures in
      patients with type 2 diabetes.

PMID- 21906119
TI  - To bleed or not to bleed. Is that the question?

PMID- 21906124
TI  - The pathogenic role of autoantibodies in pemphigus vulgaris.
AB  - Pemphigus vulgaris (PV) is a severe autoimmune bullous disease involving both the
      skin and mucosal areas, and characterized by intraepithelial flaccid blisters and
      erosions. The pathogenesis of this disease is not yet completely understood, but
      novel insights into desmoglein biology and autoantibody pathogenesis have
      recently been published. Acantholysis in PV seems to result from a collective
      action of autoantibodies against various keratinocyte self antigens, of which
      desmogleins 1 and 3 are the most important. Additional antigens including
      desmocollins and nondesmosome components, such as the mitochondrion, might take
      part in disease activation. Recently, apoptosis was reported as a possible
      underlying mechanism of acantholysis. Furthermore, apoptolysis is believed to be
      the link between suprabasal acantholytic and cell-death pathways. We review the
      possible hypotheses of the pathogenesis of PV: the desmoglein compensation
      theory, the antibody-induced apoptosis theory, the basal-cell shrinkage
      hypothesis and the newly published apoptolysis theory.

PMID- 21906120
TI  - Antiplatelet therapy: thrombin receptor antagonists.
AB  - Activated platelets stimulate thrombus formation in response to rupture of an
      atherosclerotic plaque or endothelial cell erosion, promoting atherothrombotic
      disease. Multiple pathways contribute to platelet activation. Aspirin, an
      irreversible inhibitor of thromboxane A2 synthesis, in combination with
      clopidogrel, an inhibitor of P2Y(12) adenosine diphosphate platelet receptors,
      represent the current standard-of-care of antiplatelet therapy for patients with
      acute coronary syndrome and for those undergoing percutaneous coronary
      intervention. Although these agents have demonstrated significant clinical
      benefit, the increased risk of bleeding and the recurrence of thrombotic events
      represent substantial limitations. Thrombin is one of the most important platelet
      activators. The inhibition of protease-activated receptor 1 showed a good safety
      profile in preclinical studies. In fact, phase II studies with vorapaxar
      (SCH530348) and atopaxar (E5555) showed no increase of bleeding events in
      addition to the current standard-of-care of antiplatelet therapy. Although the
      results of phase III trials for both drugs are awaited, this family is a
      promising new addition to the current clinical practice for patients with
      atherothrombotic disease, not only as an alternative, but also as additional
      therapy.

PMID- 21906121
TI  - Anti-platelet therapy: glycoprotein IIb-IIIa antagonists.
AB  - Glycoprotein (GP) IIb-IIIa antagonists inhibit the aggregation of activated
      platelets. Three agents are approved for clinical use. In this review, the
      characteristics of each agent, their pharmacodynamic profile, results in pivotal
      clinical trials and the associated clinical implications are discussed. GP IIb
      IIIa antagonists have greatest benefit when used as adjunctive therapy during
      percutaneous coronary intervention (PCI) when the patient has intra-coronary
      thrombosis. These agents appear to provide greatest benefit when used in
      combination with heparin. The clinical niche for parenteral GP IIb-IIIa
      antagonists is evolving. The rapid onset and offset of GP IIb-IIIa antagonists
      plus dosing designed to inhibit extensively platelet aggregation differentiates
      them from oral agents. The contemporary niche appears to include patients in
      transition, such as individuals requiring emergent PCI before oral agents are
      fully active and for unstable patients requiring transport to PCI centres,
      particularly in patients likely to have intracoronary thrombus. Subsequent
      studies should evaluate the optimal duration of therapy with GP IIb-IIIa
      antagonists.

PMID- 21906125
TI  - A review of the biological and clinical characteristics of luminal-like oestrogen
      receptor-positive breast cancer.
AB  - Global gene expression profiling (GEP) studies of breast cancer have identified
      distinct biological classes with different clinical and therapeutic implications.
      Oestrogen receptor (ER) has been found to be a central marker of the molecular
      signature. GEP studies have consistently recognized a molecularly distinct class
      of tumours that is characterized by high-level expression of ER and other
      biomarkers recognized to be characteristic of normal luminal cells of the breast.
      This class is the largest of the GEP-defined molecular subclasses, comprising 60
      70% of breast cancer cases. Moreover, it has been proposed that this group of
      tumours is composed of at least two subclasses distinguished by differing GEP
      profiles. At present, there is no consensus on the definition of the luminal
      subclasses and, in clinical practice, luminal-like tumours and ER-positive
      tumours are frequently considered to be the same. A better understanding of the
      biological features of luminal tumours could lead to their improved
      characterization and consistent identification. In this review, we explore the
      concept and definitions of the luminal-like class of breast carcinoma and their
      contribution to our understanding of their molecular features, clinical
      significance and therapeutic implications.

PMID- 21906127
TI  - Chromosomal aberrations as detected by array comparative genomic hybridization in
      early low-grade intraepithelial neoplasias of the breast.
AB  - AIMS: Low-grade flat ductal intraepithelial neoplasia (DIN1a, flat epithelial
      atypia) is one of the earliest morphologically recognizable neoplastic lesions of
      the breast. Frequently, it occurs concomitantly with lobular intraepithelial
      neoplasia (LIN). We aimed to elucidate chromosomal aberrations in these early
      neoplastic breast lesions with the use of array comparative genomic hybridization
      analysis. METHODS AND RESULTS: Laser capture microdissection of 12 archival
      formalin-fixed, paraffin-embedded specimens harbouring foci of both DIN1a and LIN
      was performed. All analysed cases of DIN1a and LIN showed chromosomal gains and
      losses. The aberration encountered most often was loss of 16q, noted in seven
      DIN1a (70% of those successfully examined) and 10 LIN (91%) cases. The next most
      common alteration was a gain on 1q, noted in four DIN1a (40%) and seven LIN (64%)
      cases. CONCLUSIONS: The results show concurrent chromosomal aberrations of 1q
      gains and 16q losses in several cases with coexisting LIN and DIN1a. These
      aberrations are known to be common in low-grade invasive (ductal and lobular)
      carcinomas as well as in more advanced (conventional) types of low-grade ductal
      intraepithelial neoplasia (DIN) (low-grade ductal carcinoma in situ). Our results
      raise the possibility of similar molecular-genetic pathways in coexisting LIN and
      low-grade flat DIN.

PMID- 21906126
TI  - Histological grade of invasive carcinoma of the breast assessed on needle core
      biopsy - modifications to mitotic count assessment to improve agreement with
      surgical specimens.
AB  - AIMS: Histological grade assessed on core biopsy of mammary invasive carcinomas
      tends to underestimate the grade in the excision specimen. A major factor is
      underestimation of mitoses. The aim of this study was to improve the assessment
      of mitoses in core biopsies. METHODS AND RESULTS: In a test set (100 tumours),
      reducing the threshold for a mitotic score of 2 from 11 mitoses per 10 high-power
      fields (diameter 0.61 mm) to 6/10 resulted in improved agreement between core and
      excision from 69% to 73%. In tumours graded as T3 P3 M1 (few tubules, marked
      nuclear pleomorphism and few mitoses) on core (a group with poor agreement of
      grade between core and surgical specimens), this change in threshold also
      improved agreement in four tumours. Use of the mitotic count in the core of
      axillary nodal metastasis, if higher than the count in the breast core, improved
      agreement in two patients. Use of both approaches in a validation set (349
      tumours) improved agreement from 65% to 70% in the whole group, and from 31% to
      55% in tumours scored as T3 P3 M1 on the core. CONCLUSIONS: These strategies
      improve the accuracy of grading on core biopsy and are of particular value in T3
      P3 M1 tumours.

PMID- 21906128
TI  - Much of the variation in breast pathology quality assurance data in the UK can be
      explained by the random order in which cases arrive at individual centres, but
      some true outliers do exist.
AB  - AIMS: To investigate the role of random temporal order of patient arrival at
      screening centres in the variability seen in rates of node positivity and breast
      cancer grade between centres in the NHS Breast Screening Programme. METHODS AND
      RESULTS: Computer simulations were performed of the variation in node positivity
      and breast cancer grade with the random temporal arrival of patients at screening
      centres based on national UK audit data. Cumulative mean graphs of these data
      were plotted. Confidence intervals for the parameters were generated, using the
      binomial distribution. UK audit data were plotted on these control limit graphs.
      The results showed that much of the variability in the audit data could be
      accounted for by the effects of random order of arrival of cases at the screening
      centres. Confidence intervals of 99.7% identified true outliers in the data.
      CONCLUSIONS: Much of the variation in breast pathology quality assurance data in
      the UK can be explained by the random order in which cases arrive at individual
      centres. Control charts with confidence intervals of 99.7% plotted against the
      number of reported cases are useful tools for identification of true outliers.

PMID- 21906129
TI  - Constructing tissue microarrays from core needle biopsies of breast cancers.

PMID- 21906130
TI  - Can end organ damage in scleroderma be predicted based on nail fold dermatoscopy
      findings?

PMID- 21906131
TI  - Whither nursing models? The value of nursing theory in the context of evidence
      based practice and multidisciplinary health care.
AB  - AIM: This paper presents a discussion of the role of nursing models and theory in
      the modern clinical environment. BACKGROUND: Models of nursing have had limited
      success in bridging the gap between theory and practice. DATA SOURCES: Literature
      on nursing models and theory since the 1950s, from health and social care
      databases. DISCUSSION: Arguments against nursing theory are challenged. In the
      current context of multidisciplinary services and the doctrine of evidence-based
      practice, a unique theoretical standpoint comprising the art and science of
      nursing is more relevant than ever. IMPLICATIONS FOR NURSING: A theoretical
      framework should reflect the eclectic, pragmatic practice of nursing. CONCLUSION:
      Nurse educators and practitioners should embrace theory-based practice as well as
      evidence-based practice.

PMID- 21906132
TI  - Rapidly progressive systemic sclerosis associated with breast carcinoma: report
      of a case with anti-RNA polymerase III antibody.

PMID- 21906133
TI  - Temporal triangular alopecia: trichoscopic diagnosis.

PMID- 21906134
TI  - Case of tubular apocrine adenoma with follicular differentiation located on the
      trunk.

PMID- 21906135
TI  - Livedo reticularis as an initial clinical manifestation of gemcitabine-induced
      hemolytic uremic syndrome.

PMID- 21906136
TI  - Perilipin and adipophilin expression regulated by Rho-kinase during
      differentiation of hamster sebocyte.

PMID- 21906137
TI  - Extensive subcutaneous fat necrosis of the newborn associated with therapeutic
      hypothermia.
AB  - Subcutaneous fat necrosis of the newborn is a form of panniculitis that most
      often occurs in full-term infants with predisposing risk factors. Three neonates
      with hypoxic ischemic encephalopathy were treated with therapeutic hypothermia
      and developed extensive subcutaneous fat necrosis. All three infants developed
      extensive subcutaneous fat necrosis, involving the back, scalp, and arms. Mild,
      asymptomatic hypercalcemia was noted in one infant in the weeks following the
      subcutaneous fat necrosis. Hypothermia as a risk factor for subcutaneous fat
      necrosis is reviewed. Clinicians should be aware of subcutaneous fat necrosis as
      a possible risk factor and complication associated with asphyxiated newborns who
      may undergo therapeutic hypothermia. Future studies for therapeutic hypothermia
      should evaluate neonates for the development of subcutaneous fat necrosis.

PMID- 21906138
TI  - Case report: Meningothelial hamartoma of the scalp in a 9-year-old child.
AB  - Meningothelial hamartomas represent a collection of meningothelial elements in an
      ectopic location. Lesions are histologically characterized as a proliferation of
      connective tissue elements and small- and medium-sized vessels admixed with
      meningothelial elements. Lesions are most often located on the scalp, present at
      birth, and do not extend past the subcutis. We discuss the case of a 9-year-old
      African American girl presenting with one such lesion on the parietal aspect of
      the scalp.

PMID- 21906139
TI  - Fatal leptomeningeal melanoma in neurocutaneous melanosis.
AB  - We report an unusual occurrence of a primary dural-based malignant melanoma in a
      13-year-old boy with neurocutaneous melanosis. The lesion presented with rapid
      onset symptoms characterized by raised intracranial pressure and seizures, had an
      aggressive clinical course, and proved to be fatal despite two surgeries and
      adjuvant therapy. There should be a high index of suspicion for the occurrence of
      such a malignant leptomeningeal tumor in patients with congenital melanocytic
      nevi presenting with neurological symptoms of recent onset.

PMID- 21906140
TI  - Coronary artery thickening with mucosal lesions in Henoch-Schonlein purpura.
AB  - Henoch-Schonlein purpura (HSP) is the most common vasculitis of childhood. It is
      usually self-limiting and is characterized by an immune complex-mediated
      vasculitis associated with IgA deposition. We present an unusual case of HSP with
      mucosal lesions and coronary artery thickening.

PMID- 21906141
TI  - Congenital cutaneous candidiasis in two full-term infants.
AB  - We describe two full-term infants who presented with congenital cutaneous
      candidiasis (CCC) and compare their clinical presentation and outcome with that
      of neonatal candidiasis and chronic mucocutaneous candidiasis. Although candidal
      vulvovaginitis occurs in up to one-third of pregnancies, CCC is uncommon and can
      be confused with more-serious pustular disorders that present in neonates.
      Greater awareness of CCC is essential to make an early diagnosis and distinguish
      it from other infections.

PMID- 21906142
TI  - "Alternately divided" epidermal nevus of the fingers.
AB  - A 2-year-old white girl with divided (or kissing) epidermal nevus of the third
      and fourth fingers of the left hand is described. The possible pathogenesis of
      this unique lesion is also discussed.

PMID- 21906143
TI  - Profuse congenital familial milia with absent dermatoglyphics (Basan's Syndrome):
      description of a new family.
AB  - Milia are common, small, keratin-containing cysts frequently seen in all age
      groups. They may arise spontaneously or develop after a variety of stimuli. They
      can be found alone or as part of syndromes. We present a female neonate born not
      only with profuse facial milia, but also with acral bullae and absent
      dermatoglyphics. Similar features were seen in several members of her family.
      These findings correspond to the syndrome known as Basan's syndrome, a rare
      autosomal-dominant inherited dermatosis characterized by profuse congenital
      milia, transient neonatal acral bullae, and absence of dermatoglyphics.

PMID- 21906144
TI  - A novel heterozygous point mutation in the p63 gene in a patient with ectodermal
      dysplasia associated with B-cell leukemia.
AB  - We report a 7-year-old boy with a past medical history of B-cell leukemia with
      dysmorphic features, including cleft palate, hypotrichosis with trichorrhexis
      nodosa, hypohidrosis, oligodontia, and ridging of nails. A heterozygous germline
      mutation, Ala111Thr, in the p63 gene was detected in the boy and in his mother,
      who had no clinical expression. This case emphasizes the spectrum of different
      phenotypical manifestations of mutations in the p63 gene and underlines the
      possible role of this gene as a tumor suppressor.

PMID- 21906145
TI  - Linear immunoglobulin a bullous disease of childhood responsive to intravenous
      immunoglobulin monotherapy.
AB  - We report a case of linear immunoglobulin A bullous disease in a 9-year-old boy
      who presented with rapidly progressive severe disease and could not tolerate
      dapsone because of high liver enzymes within a week after a low dose of dapsone
      in association with an underlying fatty liver. He showed remarkable improvement
      with intravenous immunoglobulins used as monotherapy, with a rapid clearance and
      a sustained remission after stopping the treatment.

PMID- 21906146
TI  - Severe cutaneous zygomycosis due to Basidiobolus ranarum in a young infant.
AB  - Basidiobolomycosis classically presents as a noninflammatory, nonulcerated,
      nontender woody indurated mass without much contiguous spread. It is almost
      always seen in an immunocompetent host younger than 20. We report a case of a 9
      month-old baby with a rapidly expanding malignant presentation of
      basidiobolomycosis with nonhealing ulcers and spread to underlying muscles,
      mimicking lymphoma. She responded poorly to itraconazole alone but showed
      dramatic improvement with a combination therapy of itraconazole and potassium
      iodide. The case also highlights an early acquisition of the infection at 1 month
      of age.

PMID- 21906147
TI  - Sturge-Weber syndrome in patients with facial port-wine stain.
AB  - Facial port-wine stain (PWS) may be associated with cerebrovascular abnormalities
      such as Sturge-Weber syndrome (SWS). In a large series, we aimed to assess which
      topography of facial PWS can predict SWS. This was a cross-sectional study of
      consecutive patients with facial PWS seen in pediatric dermatologic or
      angiodysplasia consultations from 1993 to 2005 at the University Hospital Center
      of Tours. A standardized form was used to collect data on clinical and imaging
      findings. Patients with and without SWS were compared in terms of topography of
      the cutaneous angioma and related ophthalmologic and neurologic features. Two
      hundred fifty-nine patients were included, 15 with a diagnosis of SWS. All
      patients with SWS showed involvement of the V1 trigeminal cutaneous area. SWS was
      significantly associated with bilateral topography of the PWS, its extension to
      another territory, and involvement of the upper eyelid. Knowledge of the
      topography of facial PWS with risk of associated neurological or ocular anomalies
      allows for early diagnosis of SWS and avoids unnecessary and costly radiography
      for patients with uncomplicated facial PWS.

PMID- 21906148
TI  - Acrodermatitis enteropathica: a novel SLC39A4 gene mutation found in a patient
      with an early-onset.
AB  - We report the case of a 3-month-old full-term, breast-fed infant with clinical
      and laboratorial findings consistent with acrodermatitis enteropathica. In
      addition, the mother had low zinc levels in her breast milk. Mutation analysis
      revealed a novel insertion in the SLC39A4 gene.

PMID- 21906149
TI  - Panton-Valentine leukocidin-producing Staphylococcal aureus: report of four
      siblings.
AB  - Panton-Valentine leukocidin (PVL)-producing Staphylococcus aureus results in
      leukocyte destruction and tissue necrosis (Pediatric Dermatology 2007;24:401). It
      can be associated with a spectrum of clinical manifestations that range from
      localized staphylococcal skin infections to sometimes severe necrotizing
      pneumonia (Clin Infect Dis 1999;29:1128). We report a case of four siblings,
      three brothers whose atopic dermatitis was complicated by cutaneous lesions and
      furunculosis, while their 21-month-old sister had a fatal PVL positive
      staphylococcal pneumonia.

PMID- 21906150
TI  - Neonatal linear immunoglobulin a bullous dermatosis: a rare presentation.
AB  - Linear immunoglobulin A bullous dermatosis (LABD) is an autoimmune blistering
      disease that most commonly presents in preschool-aged children. There have been
      few neonatal reports, all of which had life-threatening aerodigestive
      complications requiring mechanical intervention and systemic therapy. We present
      a case of LABD in a neonate who had an uncomplicated course and was treated
      conservatively with only low-potency topical corticosteroids and wound care
      before resolution of his skin lesions.

PMID- 21906151
TI  - Frontal congenital lipoma.
AB  - Frontonasal dysplasia (FND) is a rare syndrome characterized by malformations of
      the central portion of the face, especially of the forehead, nose, and philtrum.
      FND is associated with hypertelorism, a hidden encephalocele, and a cleft of the
      nose. Occasionally, affected individuals also experience abnormalities of the
      brain and craniofacial bones. In such cases, a frontal lipoma or calcification of
      the falx cerebri suggest the existence of a lipoma of the corpus callosum. We
      present the case of a male newborn with a congenital lipoma 15 mm in size located
      in the medial frontal line. Magnetic resonance imaging confirmed complete
      agenesis of the corpus callosum. While there is controversy about the association
      of frontal lipoma and lipoma of the corpus callosum and FND, we believe our case
      supports the concept that the changes are due to the same underlying pathogenic
      mechanism. Therefore, we recommend imaging of the central nervous system in
      newborns with a congenital lipoma located in the craniofacial midline.

PMID- 21906152
TI  - Kawasaki disease and alopecia areata: coincidence or a true association?
AB  - A 10-year-old boy presented with fever, stiff neck, and rash over the legs.
      During the course of his hospital stay, the clinical picture gradually evolved,
      and he met the criteria for Kawasaki disease (KD) on the seventh day of
      hospitalization. During this period, he also developed alopecia areata. He was
      managed with intravenous immunoglobulin, aspirin, and intralesional
      triamcinolone. This is the first case of alopecia areata with KD in the
      literature, and it does not appear to be a mere coincidence. We discuss the
      probable mechanisms of alopecia areata with KD, an association that has not been
      reported before.

PMID- 21906153
TI  - Familial androgenetic alopecia in siblings with normal endocrinological status.
AB  - Androgenetic alopecia (AGA) is the most common type of hair loss in adults, but
      it has been rarely reported in children. We report two cases of AGA in two
      siblings, aged 6 and 8, whose mother had the same condition, without any
      association with other skin diseases or abnormalities in endocrinologic
      examinations.

PMID- 21906154
TI  - Opalescent grouped vesicles over the face: an important indicator of
      staphylococcal septicemia.
AB  - We present a report of three cases with vesicles containing opalescent fluid
      grouped over the face and scattered on the trunk and limbs. Culture of the fluid
      aspirated from the vesicles grew Staphylococcus aureus in two of the three cases.
      The observation of vesicles grouped on the face in a sick febrile child should
      prompt the diagnosis of a severe staphylococcal septicemia.

PMID- 21906155
TI  - Cutaneous mastocytosis exacerbated by pinworms in a young boy.
AB  - Cutaneous mastocytosis in children has an indolent course and undergoes
      spontaneous regression. Many triggering factors may cause mast cell degranulation
      and clinical manifestations. Knowledge of these factors is important for patients
      and their families. We report a case of exacerbation of urticaria pigmentosa due
      to mast cell degranulation caused by Enterobius vermicularis, which has not been
      reported before as a triggering factor.

PMID- 21906156
TI  - Febrile ulceronecrotic Mucha-Habermann disease in a 34-month-old boy: a case
      report and review of the literature.
AB  - We report a case of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) in a
      34-month-old boy. Our patient had a history of biopsy-proven pityriasis
      lichenoides et varioliformis acuta (PLEVA) since age 2. At 34 months, his skin
      lesions rapidly progressed to ulceration and necrosis in the setting of high
      fever. Skin biopsy revealed an intense lichenoid infiltrate with parakeratosis at
      the edges of areas of epidermal necrosis consistent with FUMHD, which is the
      severe variant of PLEVA. Despite initial treatment with prednisolone, his disease
      progressed to involve more than 50% of his body surface area. In addition to
      corticosteroids, he was treated with intravenous immunoglobulin, dapsone, and
      acyclovir, without complete resolution of disease. Methotrexate successfully
      cleared his skin disease and systemic symptoms. This patient highlights the
      exceptional response of FUMHD to methotrexate. Based on our review of the
      literature, this also represents the youngest reported case of FUMHD.

PMID- 21906157
TI  - Multiple cutaneous plexiform schwannomas as initial presentation of
      neurofibromatosis 2 in a 9-year-old.
AB  - Neurofibromatosis 2 (NF2) is an autosomal-dominant disease caused by genetic
      mutations of the NF2 gene on chromosome 22. Patients are often diagnosed
      according to the presence of bilateral vestibular schwannomas and other tumors in
      the brain and spinal cord. In children, NF2 can present early with ocular
      findings and cutaneous tumors. We report here a 9-year-old girl who presented
      with multiple pigmented, slightly tender plaques on her scalp, face, and back
      that were revealed by histopathology to be plexiform schwannomas. We suspected
      NF2 and sent the patient's blood for genetic testing, which confirmed our
      diagnosis.

PMID- 21906158
TI  - Coexistence of two atypical variants of pityriasis rosea: a case report and
      review of literature.
AB  - We report the case of a 16-year-old Indian girl who presented with multiple small
      papular lesions and larger erythema multiforme-like plaques in a Christmas tree
      pattern over her body for 3 weeks. Histopathologic examination was performed, and
      she was diagnosed with pityriasis rosea presenting with two atypical
      morphological variants-generalized papular and erythema multiforme-like. A brief
      review of literature of these two rare types is also presented.

PMID- 21906159
TI  - Aneurysmal dilatation of the inferior vena cava.
AB  - AIM: Inferior vena cava aneurysms (IVCA) are rare, unlike aortic aneurysms. The
      diagnosis and treatment is challenging. This study defines clinical and
      echocardiographic findings in a prospective cohort of sixteen patients with
      fusiform IVCA. METHODS AND RESULTS: All patients referred to the Mayo Clinic
      between January 2006 and July 2009 for a clinically indicated echocardiogram
      (36,128 patients) were screened for a dilated IVC. Sixteen cases of fusiform IVCA
      were identified. Eleven cases (68.8%) were female. Mean age at presentation was
      76 years (range 51-89). Eleven (68.8%) had structural heart disease: with right
      ventricular (RV) dysfunction in 45.5% (n = 5), moderate or greater tricuspid
      regurgitation (TR) was seen in 36.4% (n = 4) and RV enlargement was seen in 18.2%
      (n = 2). The most common clinical indication for echocardiography was dyspnea
      (25%; n = 4) and heart failure (18.8%; n = 3). The mean IVCA diameter was 4.1 cm
      (range 3.8-5 cm) and the mean length of the aneurysms was 6.2 cm (range 3.5-8.7
      cm), with mean right ventricular systolic pressure of 55 mmHg (range 31-105
      mmHg). Five (31.3%) had at least a moderate reduction in right ventricular
      ejection fraction and five (31.3%) had significant TR. Among these five patients
      with significant TR, severe TR was present in 80%; (n = 4) and moderate to severe
      TR was present in 20%; (n = 1). CONCLUSIONS: IVC aneurysms are more common in the
      elderly, and is associated with an increase in right sided heart pressures,
      significant TR, and RV dysfunction.

PMID- 21906161
TI  - Echo Doppler predictors of pulmonary artery hypertension in patients with
      systemic sclerosis.
AB  - OBJECTIVES: Evaluate echocardiographic predictors of pulmonary artery
      hypertension (PAH) in a prospective cohort of patients with systemic sclerosis
      (SSc). METHODS: 38 patients with SSc who did not have PAH and significant left
      heart disease, with peak tricuspid regurgitant velocity (TRV) <= 2.8 m/sec and
      systolic pulmonary artery pressure (sPAP) < 40 mmHg on echo Doppler were
      enrolled. Patients underwent: clinical assessment, NT-proBNP, and DLco
      measurements. Echo Doppler evaluation included right ventricular (RV) dimensions,
      tricuspid annular plan systolic excursion, fractional area change, tricuspid DTI
      systolic velocity, Tei index, pulmonary flow acceleration time (AcT), ratio of
      TRV to RV outflow tract time-velocity integral (TVI) and a parameter of disturbed
      RV ejection (TRV/AcT). After a planned 12-month follow-up we evaluated the
      predictive value of these parameters for the development of PAH, as demonstrated
      by right heart catheterization (RHC). Criteria for RHC were TRV >= 3 m/sec or
      sPAP >= 40 mmHg. RESULTS: Four patients developed PAH. Only TRV/TVI and TRV/AcT
      ratios significantly predicted PAH development (TRV/TVI ratio >= 0.16 [predefined
      and ROC confirmed]: OR 99, CI 95%: 4.865-2015, P = 0.004; TRV/AcT ratio >= 0.022
      [predefined and ROC confirmed]: OR 12.68, CI 95% 1.163-379.3, P = 0.036). Both
      parameters showed a good diagnostic power (TRV/TVI ratio: ROC area 79%,
      sensitivity 75%, specificity 97% and diagnostic accuracy 94.74% for cutoff value
      of 0.16; TRV/AcT ratio: ROC area 75%, sensitivity 75%, specificity 71% and
      diagnostic accuracy 72% for cutoff value of 0.022). CONCLUSIONS: This prospective
      study identified increased values of the two ratios TRV/TVI and TRV/AcT as
      predictors of PAH in SSc.

PMID- 21906162
TI  - Subclinical left ventricular dysfunction in asymptomatic chronic mitral
      regurgitation patients with normal ejection fraction: a combined tissue Doppler
      and velocity vector imaging-based study.
AB  - BACKGROUND: The optimal timing of the surgery in asymptomatic severe mitral
      regurgitation (MR) remains a challenge. The aim of the study is to evaluate the
      subclinical changes in LV longitudinal functions by using a novel strain imaging
      technique; velocity vector imaging (VVI); in patients with chronic MR. METHODS
      AND RESULTS: We studied 54 patients with asymptomatic, nonischemic, chronic MR
      (56.8 +/- 9 years and 56% male) and 30 healthy controls (55 +/- 6.5 years and 55%
      male) with normal ejection fraction. Patients with MR were analyzed in tertiles
      according to their regurgitant volumes (RV) and regurgitant fractions (RF): mild
      MR (RV < 30 mL, RF < 30% n = 7), moderate MR (RV: 30-59 mL, RF = 30-50%; n = 29),
      and severe MR (RV > 60 mL, RF >= 50%; n = 18). Conventional echocardiography and
      VVI-based strain imaging were performed to analyze LV functions. LV longitudinal
      peak systolic strain and strain rate (SRs) were significantly impaired in
      moderate and severe MR patients. Changes in LV longitudinal deformation were more
      significant in patients with severe MR. All deformation parameters showed a
      marked negative correlation with RV (LV Strain r =-0.583, P = 0.0001; LV SR r =
      0.408, P = 0.002, respectively). CONCLUSIONS: LV long-axis functions are
      important markers of LV contractility in MR patients. Novel echocardiographic
      techniques may provide additional data on subclinical changes in the LV and give
      way to the optimal timing for the surgery in severe MR patients.

PMID- 21906163
TI  - Progressive subclinical left ventricular systolic dysfunction in severe aortic
      regurgitation patients with normal ejection fraction: a 24 months follow-up
      velocity vector imaging study.
AB  - OBJECTIVES: We aimed to evaluate long-term changes in left ventricular (LV)
      longitudinal systolic functions in patients with asymptomatic, severe aortic
      regurgitation (AR) by using novel 2D strain imaging. METHODS AND RESULTS: Thirty
      severe AR patients with normal ejection fraction (EF) and 30 healthy controls
      were evaluated by both conventional echocardiography and velocity vector maging
      (VVI) based strain imaging at baseline and 24 months follow-up. To evaluate LV
      longitudinal systolic function, segmental peak systolic strain and strain rate
      (SRs) data were acquired from apical four-chamber, two-chamber and long-axis
      views. Longitudinal peak systolic strain and SRs of the LV were decreased in
      patients with severe AR compared to controls at baseline (P = 0.0001). The
      impairment was more significant in 24 months follow-up (P = 0.0001 for strain, P
      = 0.01 for SRs). Longitudinal peak systolic strain was significantly correlated
      with left ventricular end-diastolic (LVEDD; r =-0.42, P = 0.0001) and left
      ventricular end-systolic diameter (LVESD) (r =-0.41, P = 0.0001) There was also a
      strong negative correlation between LV SRs and LVEDD (r =-0.50, P = 0.0001), and
      LVESD (r =-0.39, P = 0.0001). CONCLUSIONS: VVI-derived strain and SRs may be used
      as adjunctive, noninvasive parameters in the assessment of subclinical LV
      dysfunction and its progress during clinical follow-up, in patients with severe
      AR.

PMID- 21906164
TI  - Management of coronary artery disease in end-stage renal disease.
AB  - Despite a substantial number of patients with end-stage renal disease who have
      coronary artery disease, the comparative effectiveness of revascularization
      procedures such as coronary artery bypass grafting and percutaneous coronary
      intervention remain unclear. Innovations in the field of coronary artery
      revascularization and concomitant changes in the standard of practice have
      improved outcomes in general. However, meaningful clinical decision-making
      remains difficult because it requires clinicians to extrapolate evidence derived
      from studies in the general population to patients with kidney disease for whom
      there is limited information from intervention trials. In non-randomized studies,
      this high-risk population for cardiovascular morbidity and mortality appear to
      derive substantial benefits from coronary revascularization. However, specific
      treatment decisions are often made based upon individual circumstances and
      contexts that are not well captured in these studies. This article reviews the
      available evidence, and its limitations, for deciding between various
      revascularization strategies for patients with end-stage renal disease. Several
      considerations that arise while making such decisions are discussed.

PMID- 21906165
TI  - Erythropoietin-stimulating agents in chronic kidney disease: a response to
      hyporesponsiveness.
AB  - Hyporesponsiveness to erythropoietin stimulating agents occurs frequently, and
      may be observed at initiation of treatment or during maintenance therapy. An
      inverse relationship between hyporesponsiveness and incident cardiovascular
      events has been reported. It is related at least in part to co-morbidity and its
      occurrence requires a search for the cause. Treatment of anemia in hyporesponsive
      patients should be individualized, with consideration given to the indication for
      ESA therapy, the target hemoglobin for therapy, and maximal dose limitations.

PMID- 21906167
TI  - Conditionally funded field evaluations--a solution to the economic barriers
      limiting evidence generation in dialysis?
AB  - Evaluation of new therapies after licensing is usually a binary decision by
      payers; to fund or not to fund. In the real world, many therapies fall into a
      gray zone of incomplete evaluation. Many clinical and economic issues in
      nephrology have combined to create a long list of such promising but incompletely
      evaluated therapies. This article focuses on the economic challenges that limit
      evidence generation in nephrology. Conditionally funded field evaluations such as
      coverage with evidence development can allow both earlier access to new
      treatments and rigorous evaluation. The authors propose that field evaluations
      will stimulate an environment that promotes pivotal renal care advances.
      Certainly, the evidence challenge faced by nephrology requires urgent discussions
      on creating conditions that catalyze and accelerate innovation, and improve
      patient outcomes.

PMID- 21906166
TI  - Standardized definitions for hemodialysis vascular access.
AB  - Vascular access dysfunction is one of the leading causes of morbidity and
      mortality among end-stage renal disease patients. Vascular access dysfunction
      exists in all three types of available accesses: arteriovenous fistulas,
      arteriovenous grafts, and tunneled catheters. To improve clinical research and
      outcomes in hemodialysis (HD) access dysfunction, the development of a
      multidisciplinary network of collaborative investigators with various areas of
      expertise, and common standards for terminology and classification in all
      vascular access types, is required. The North American Vascular Access Consortium
      (NAVAC) is a newly formed multidisciplinary and multicenter network of experts in
      the area of HD vascular access, who include nephrologists and interventional
      nephrologists from the United States and Canada with: (1) a primary clinical and
      research focus in HD vascular access dysfunction, (2) national and
      internationally recognized experts in vascular access, and (3) a history of
      productivity measured by peer-reviewed publications and funding among members of
      this consortium. The consortium's mission is to improve the quality and
      efficiency in vascular access research, and impact the research in the area of HD
      vascular access by conducting observational studies and randomized controlled
      trials. The purpose of the consortium's initial manuscript is to provide working
      and standard vascular access definitions relating to (1) epidemiology, (2)
      vascular access function, (3) vascular access patency, and (4) complications in
      vascular accesses relating to each of the vascular access types.

PMID- 21906169
TI  - Anemia and iron management.

PMID- 21906168
TI  - A proposed approach to the dialysis prescription in severely hyponatremic
      patients with end-stage renal disease.
AB  - Patients with renal failure and severe hyponatremia present a therapeutic
      dilemma. Conventional hemodialysis is necessary to correct blood chemistries and
      volume overload, yet it may raise serum sodium (Na) too quickly, potentially
      resulting in osmotic demyelination syndrome. We present the case of a patient who
      presented with renal failure requiring dialysis and also with a serum Na of 112
      mEq/l. Using a dialysate Na concentration of 130 mEq/l and by limiting the blood
      flow to 50 ml/minute, we were able to raise her serum Na by only 2 mEq/l/hour
      during her hemodialysis treatment and thus control both the rate and total change
      in the patient's serum Na.

PMID- 21906170
TI  - Impact of the ratio of graft kidney volume to recipient body surface area on
      graft function after live donor kidney transplantation.
AB  - Functioning nephron mass is a determinant of the graft function of kidney
      transplant recipients. The graft kidney volume and its weight have been reported
      to be surrogates of the nephron mass. To investigate the impact of the ratios of
      the surrogates to recipient body surface area (BSA) and body weight on the graft
      function within six months post-transplantation, we measured the graft kidney
      volume, using computed tomography with 3-dimensional reconstruction before
      transplantation, and measured the graft kidney weight during surgery. Ninety-four
      cases of live donor kidney transplants were included in this study. The graft
      kidney volume/recipient BSA ratio was correlated with the glomerular filtration
      rate (GFR) of recipients at one and six months post-transplantation (r = 0.416, p
      < 0.001 and r = 0.381, p < 0.001, respectively). We found a difference in the
      graft function between recipients with a graft kidney volume/recipient BSA ratio
      of >=90.9 mL/m(2) and those with a ratio of <90.9 mL/m(2) (p < 0.001).
      Multivariate analysis demonstrated that the graft kidney volume/recipient BSA
      ratio and donor age are independent predictors of recipient GFR at one and six
      months post-transplantation (p < 0.05). During living donor and recipient
      matching, both the potential volume of the donated kidney and the body size of
      recipient should be considered.

PMID- 21906171
TI  - Age, gender, and body mass index are associated with renal function after kidney
      donation.
AB  - Renal function is thoroughly evaluated before live kidney donation. However, some
      donors experience impaired recovery of renal function after donation. Our aim was
      to assess estimated glomerular filtration rate (eGFR) and mean relative (%)
      increase in creatinine one yr after donor nephrectomy. The study was based on
      retrospective data from kidney donors during the period 1997-2009. Pre-operative
      and one-yr follow-up data were available for 721 of 1067 donors. Mean relative
      increase in creatinine and eGFR were stratified by gender, body mass index (BMI),
      and age at donation. At one yr post-donation, overweight (BMI > 5 kg/m(2) ) women
      50 yr or older experienced the lowest eGFR of 49.6 +/- 8.8 mL/min/1.73 m(2) . Men
      younger than 50 yr with normal weight (BMI < 25 kg/m(2) ) had the highest eGFR of
      66.6 +/- 10.4 mL/min/1.73 m(2) . Overweight men 50 yr or older had the highest
      relative increase in creatinine of 49.4% compared to pre-donation. Men under 50
      yr with normal weight had the smallest increase in creatinine of 35.2%. In
      multivariate analysis, older age (p < 0.001), male gender (p < 0.001), and
      overweight (p = 0.01) were associated with relative increase in creatinine after
      donation. Potential donors should be offered counseling regarding overweight, as
      this is a modifiable risk factor.

PMID- 21906172
TI  - Clinical application of mTORi based immunosuppression for renal transplantation
      in India.
AB  - Long-term renal graft survival is hampered by allograft dysfunction and
      cardiovascular disease resulting from calcineurin inhibitors (CNIs). This has led
      to the development of immunosuppressive regimens involving mammalian target of
      rapamaycin (mTOR) inhibitors, sirolimus and everolimus. They seem to provide long
      term benefits for kidney function in transplant patients because of their anti
      proliferation and anti-tumor properties and absence of nephrotoxicity. Their use
      has been evaluated in therapeutic regimens aimed at reducing the nephrotoxicity
      associated with CNIs. Both proactive and reactive strategies have been used.
      Whether existing strategies of using mTORi in renal transplantation is applicable
      for Indian patient's remains to be seen. Data on side effect profile, economic
      viability and the impact of these drugs on infections, particularly in India, are
      worth documenting. After briefly reviewing available data from India, this
      article explores the indications, patient populations; timing and practical
      aspects as well as the safety and efficacy of mTORi-based regimens for renal
      transplantation and suggests a framework which could allow transplant physicians
      to tailor its use to their own practice with particular reference to the Indian
      subcontinent.

PMID- 21906173
TI  - The Right Organ for the Right Recipient: the Ninth Annual American Society of
      Transplant Surgeons' State-of-the-Art Winter Symposium.
AB  - With an increasing number of individuals with end-stage organ disease and the
      increasing success of organ transplantation, the demand for transplants has
      steadily increased. This growth has led to a greater need to utilize organs from
      as many donors as possible. As selection criteria have become less stringent to
      accommodate increasing demand, transplant outcomes are more strongly influenced
      by recipient and donor factors; thus, finding the right organ for the right
      recipient is more important than ever. The Ninth Annual American Society of
      Transplant Surgeons (ASTS) State-of-the-Art Winter Symposium, entitled "The Right
      Organ for the Right Recipient," addressed the matching of donor organs to
      appropriate recipients. Representative dilemmas in the matching of donor organs
      with recipients were discussed. These included the following: matching by donor
      and recipient risk characteristics; use of organs with risk for disease
      transmission; biologic incompatibility; use of organs from donors after cardiac
      death; the justification for combined organ transplants like liver-kidney and
      kidney-pancreas; and the role of allocation in facilitating the matching of
      donors and recipients. Regardless of the particular issue, decisions about donor
      recipient matching should be evidence-based, practical, and made with the goal of
      maximizing organ utilization while still protecting individual patient interests.

PMID- 21906174
TI  - Oral motor performance in spastic cerebral palsy individuals: are hydration and
      nutritional status associated?
AB  - BACKGROUND: Previous studies reported alterations in salivary parameters in
      cerebral palsy (CP) individuals; however, none of these considered oral motor
      performance as possibly responsible for these conditions. The aim of this study
      was to investigate the influence of oral motor performance on the nutritional
      status and salivary parameters in individuals with CP. METHODS: Forty-three
      individuals aged 11-19 years-old, with spastic CP were included in this study.
      Oral motor performance was evaluated using the Oral Motor Assessment Scale, which
      classified the individuals into two groups: subfunctional or functional.
      Unstimulated saliva was collected and the flow rate was calculated (ml/min).
      Salivary osmolality was measured using a freezing point depression osmometer.
      Blood samples were collected to evaluate complete blood count, total protein,
      albumin/globulin ratio and transferrin levels. RESULTS: The subfunctional (n =
      21) and the functional group (n = 22) did not differ regarding sex (P = 0.193),
      however the functional group was older (P = 0.023) and had a higher mean BMI (P <
      0.001). The subfunctional CP group presented a reduction in salivary flow rate
      (36.4%) (P < 0.01) and an increase in salivary osmolality (35.5%) (P < 0.001)
      compared to the functional group. Slightly lower values for red blood cells
      (millions/mm(3) ) (P < 0.001), hemoglobin (g/dl) (P < 0.009), hematocrit (%) (P =
      0.001), number of platelets (N/mm(3) ), total protein (g/dl) and albumin/globulin
      ratio (P = 0.003 and P = 0.036, respectively) were determined for the
      subfunctional group, but within the normal range of normality. CONCLUSION:
      Cerebral palsy individuals appear to present impaired adequate hydration due to
      compromised oral motor performance.

PMID- 21906175
TI  - Norovirus, gastroenteritis, and indoor environmental quality.

PMID- 21906176
TI  - Geographical variation and the determinants of domestic endotoxin levels in
      mattress dust in Europe.
AB  - Endotoxin exposures have manifold effects on human health. The geographical
      variation and determinants of domestic endotoxin levels in Europe have not yet
      been extensively described. To investigate the geographical variation and
      determinants of domestic endotoxin concentrations in mattress dust in Europe
      using data collected in the European Community Respiratory Health Survey follow
      up (ECRHS II). Endotoxin levels were measured in mattress dust from 974 ECRHS II
      participants from 22 study centers using an immunoassay. Information on
      demographic, lifestyle, and housing characteristics of the participants was
      obtained in face-to-face interviews. The median endotoxin concentration in
      mattress dust ranged from 772 endotoxin units per gram (EU/g) dust in Reykjavik,
      Iceland, to 4806 EU/g in Turin, Italy. High average outdoor summer temperature of
      study center, cat or dog keeping, a high household crowding index, and visible
      damp patches in the bedroom were significantly associated with a higher endotoxin
      concentrations in mattress dust. There is a large variability in domestic
      endotoxin levels across Europe. Average outdoor summer temperature of study
      center, which explains only 10% of the variation in domestic endotoxin level by
      center, is the strongest meteorological determinant. The observed variation needs
      to be taken into account when evaluating the health effects of endotoxin
      exposures in international contexts. PRACTICAL IMPLICATIONS: The incoherent
      observations of the health effects of endotoxin may be partly owing to the
      geographical heterogeneity of endotoxin exposure. Therefore, the observed
      variation should be considered in further studies. Measurements of indoor
      endotoxin are recommended as an indicator for the level of exposures of
      individual domestic environments.

PMID- 21906177
TI  - Large-eddy simulation of human-induced contaminant transport in room
      compartments.
AB  - A large-eddy simulation is used to investigate contaminant transport owing to
      complex human and door motions and vent-system activity in room compartments
      where a contaminated and clean room are connected by a vestibule. Human and door
      motions are simulated with an immersed boundary procedure. We demonstrate the
      details of contaminant transport owing to human- and door-motion-induced wake
      development during a short-duration event involving the movement of a person (or
      persons) from a contaminated room, through a vestibule, into a clean room.
      Parametric studies that capture the effects of human walking pattern, door
      operation, over-pressure level, and vestibule size are systematically conducted.
      A faster walking speed results in less mass transport from the contaminated room
      into the clean room. The net effect of increasing the volume of the vestibule is
      to reduce the contaminant transport. The results show that swinging-door motion
      is the dominant transport mechanism and that human-induced wake motion enhances
      compartment-to-compartment transport. PRACTICAL IMPLICATIONS: The effect of human
      activity on contaminant transport may be important in design and operation of
      clean or isolation rooms in chemical or pharmaceutical industries and intensive
      care units for airborne infectious disease control in a hospital. The present
      simulations demonstrate details of contaminant transport in such indoor
      environments during human motion events and show that simulation-based
      sensitivity analysis can be utilized for the diagnosis of contaminant
      infiltration and for better environmental protection.

PMID- 21906178
TI  - The economics of successes and failures in animal breeding.

PMID- 21906179
TI  - Building phenotype networks to improve QTL detection: a comparative analysis of
      fatty acid and fat traits in pigs.
AB  - Models in QTL mapping can be improved by considering all potential variables,
      i.e. we can use remaining traits other than the trait under study as potential
      predictors. QTL mapping is often conducted by correcting for a few fixed effects
      or covariates (e.g. sex, age), although many traits with potential causal
      relationships between them are recorded. In this work, we evaluate by simulation
      several procedures to identify optimum models in QTL scans: forward selection,
      undirected dependency graph and QTL-directed dependency graph (QDG). The latter,
      QDG, performed better in terms of power and false discovery rate and was applied
      to fatty acid (FA) composition and fat deposition traits in two pig F2 crosses
      from China and Spain. Compared with the typical QTL mapping, QDG approach
      revealed several new QTL. To the contrary, several FA QTL on chromosome 4 (e.g.
      Palmitic, C16:0; Stearic, C18:0) detected by typical mapping vanished after
      adjusting for phenotypic covariates in QDG mapping. This suggests that the QTL
      detected in typical mapping could be indirect. When a QTL is supported by both
      approaches, there is an increased confidence that the QTL have a primary effect
      on the corresponding trait. An example is a QTL for C16:1 on chromosome 8. In
      conclusion, mapping QTL based on causal phenotypic networks can increase power
      and help to make more biologically sound hypothesis on the genetic architecture
      of complex traits.

PMID- 21906180
TI  - Expression study on the porcine PTHLH gene and its relationship with sow teat
      number.
AB  - Teat number is an important trait in sows that should accompany the increase in
      litter size that has been achieved in the last decades through selection. We have
      previously identified a genome-wide significant QTL for teat number in porcine
      chromosome SSC5 by means of an experimental Meishan by Iberian F(2) intercross
      population. In the present report, we have studied the porcine parathyroid
      hormone-like hormone (PTHLH) gene, which maps to SSC5, as a candidate gene for
      this trait, as PTHLH is involved in nipple formation during embryogenesis and
      nipple development during pregnancy and lactation. We have found that porcine
      PTHLH gene is transcribed into three mRNA species differing in the 5'UTR region.
      Two of these variants are reported in pigs here for the first time: one was
      similar to variant 1 described in humans while the other, which was generated by
      the retention of two small introns, has not been identified before in any other
      species. In addition, mRNA expression profile for two of the mRNA variants was
      assessed in 19 pig tissues. Porcine PTHLH showed a widespread expression as it
      was present in all tested tissues and relative expression of each variant was
      tissue dependent. Finally, we have performed an association study between a non
      synonymous mutation in the coding region of this gene and sow teat number. The
      PTHLH polymorphism was segregating in our Meishan by Iberian F(2) population at
      intermediate allelic frequencies. We compared here six different statistical
      models to choose the one with a better fit and a lower degree of complexity.
      However, despite the potential negative effect of the PTHLH mutation in the
      signal peptide of this protein, we did not detect any association between the
      PTHLH genotype and the sow teat number phenotype, concluding that the causal
      mutation of the observed QTL is very likely not related to this gene.

PMID- 21906181
TI  - Use of bioinformatic SNP predictions in differentially expressed genes to find
      SNPs associated with Salmonella colonization in swine.
AB  - Asymptomatic Salmonella-carrier pigs present a major problem in preharvest food
      safety, with a recent survey indicating >50% of swine herds in the United States
      have Salmonella-positive animals. Salmonella-carrier pigs serve as a reservoir
      for contamination of neighbouring pigs, abattoir pens and pork products. In
      addition, fresh produce as well as water can be contaminated with Salmonella from
      manure used as fertilizer. Control of Salmonella at the farm level could be
      through genetic improvement of porcine disease resistance, a potentially powerful
      method of addressing preharvest pork safety. In this research, we integrate gene
      expression profiling data and sequence alignment-based prediction of single
      nucleotide polymorphisms (SNPs) to successfully identify SNPs in functional
      candidate genes to test for the associations with swine response to Salmonella. A
      list of 2527 genes that were differentially regulated in porcine whole blood in
      response to infection with Salmonella enterica serovar Typhimurium were selected.
      In those genes, SNPs were predicted using ANEXdb alignments based on stringent
      clustering of all publically available porcine cDNA and expressed sequence tag
      (EST) sequences. A set of 30 mostly non-synonymous SNPs were selected for
      genotype analysis of four independent populations (n = 750) with Salmonella
      faecal shedding or tissue colonization phenotypes. Nine SNPs segregated with
      minor allele frequency >=15% in at least two populations. Statistical analysis
      revealed SNPs associated with Salmonella shedding, such as haptoglobin (HP, p =
      0.001, q = 0.01), neutrophil cytosolic factor 2 (NCF2 #2, p = 0.04, q = 0.21) and
      phosphogluconate dehydrogenase (p = 0.066, q = 0.21). These associations may be
      useful in identifying and selecting pigs with improved resistance to this
      bacterium.

PMID- 21906182
TI  - Fine-mapping of quantitative trait loci for body weight and bone traits and
      positional cloning of the RB1 gene in chicken.
AB  - Previously, a quantitative trait locus (QTL) that affects body weight (BW) at 4
      12 weeks of age and carcass weight at 12 weeks of age had been mapped on chicken
      chromosome 1. After including more markers and individuals, the confidence
      interval was narrowed down to approximately 5.5 Mbps and located this QTL near a
      microsatellite marker (ADL328). This QTL is the same as the QTL for 12 bone
      traits, including metatarsus length and metatarsus circumference at 4, 6, 8, 10
      and 12 weeks of age and keel length and metatarsus claw weight at 12 weeks of
      age, that was identified using the same population. In the current study, 1010
      individuals from the Northeast Agricultural University F(2) resource population
      were used and 14 single-nucleotide polymorphism (SNPs) around ADL328 were
      developed to construct haplotypes, and an association analysis was performed to
      fine-map the QTL. The haplotypes were constructed on the basis of a sliding
      'window', with three SNP markers included in each 'window'. The association
      analysis results indicated that the haplotypes in 'windows' 6-12 were
      significantly associated with BW and bone traits and suggested that the QTL for
      BW and bone traits was located between SNP8 and SNP14 or was in linkage
      disequilibrium with this region. The interval from SNP8 to SNP14 was
      approximately 400 kbps. This region contained five RefSeq genes (RB1, P2RY5,
      FNDC3A, MLNR and CAB39L) on the University of California Santa Cruz website. The
      RB1 gene was selected as a candidate gene and five SNPs were identified in the
      gene. The association results indicated that the RB1 gene was a major gene for BW
      and bone traits. The SNPs g.39692 G>A and g.77260 A>G in RB1 gene might be two
      quantitative trait nucleotides for BW and bone traits.

PMID- 21906183
TI  - Association test between haplotypes and longitudinal traits in complex pedigrees.
AB  - Evaluating the association of candidate genes with longitudinal traits would be a
      useful method to study the genetic basis of complex traits. Haplotypes
      incorporate more information about the underlying polymorphisms than do genotypes
      for individual SNP, and have been considered as a more informative format of data
      in association analysis. In this study, we extended the random regression model
      to allow analysing haplotype effects in a longitudinal framework and then
      performed a hierarchical Bayesian method to estimate parameter values. We
      assessed the performance of the proposed approach and demonstrated its validity
      and power with simulation. The power of our method was also demonstrated by an
      example of Meishan pigs, in which one haplotype affecting the total number of
      piglets born was detected using our method, whereas it cannot be detected using
      the conventional single SNP-based model. Additionally, the model is flexible to
      be extended to model a complex network of genetic regulation that includes the
      interactions between different haplotypes and between haplotypes and
      environments.

PMID- 21906184
TI  - Evaluation of the utility of diagonal elements of the genomic relationship matrix
      as a diagnostic tool to detect mislabelled genotyped animals in a broiler chicken
      population.
AB  - This study explored distributions of diagonal elements of genomic relationship
      matrix (G), evaluated the utility of G as a diagnostic tool to detect mislabelled
      animals in a genomic dataset and evaluated the effect of mislabelled animals on
      the accuracy of genomic evaluation. Populations of 10 000 animals were simulated
      with 60 000 SNP varying in allele frequency at each locus between 0.02 and 0.98.
      Diagonal elements of G were distributed with a single peak (mean = 1.00 +/- 0.03)
      and ranged from 0.84 through 1.36. Mixed populations were also simulated: 7 000
      animals with frequencies of second alleles ranging from 0.02 through 0.98 were
      combined with 1750 or 7000 animals with frequencies of second alleles ranging
      from 0.0 through 1.0. The resulting distributions of diagonal elements of G were
      bimodal. Body weight at 6 weeks was provided by Cobb-Vantress for broiler
      chickens, of which 3285 were genotyped for 57 636 SNP. Analysis used a combined
      genomic and pedigree relationship matrix; G was scaled using current allele
      frequencies. The distribution of diagonal elements was multimodal and ranged from
      0.54 to 3.23. Animals with diagonal elements >1.5 were identified as coming from
      another chicken line or as having low call rates. Removal of mislabelled animals
      increased accuracy by 0.01. For the studied type of population, diagonal elements
      of G may be a useful tool to help identify mislabelled animals or secondary
      populations.

PMID- 21906185
TI  - Genetic diversity in an indigenous horse breed: implications for mating
      strategies and the control of future inbreeding.
AB  - The Franches-Montagnes is an indigenous Swiss horse breed, with approximately
      2500 foalings per year. The stud book is closed, and no introgression from other
      horse breeds was conducted since 1998. Since 2006, breeding values for 43
      different traits (conformation, performance and coat colour) are estimated with a
      best linear unbiased prediction (BLUP) multiple trait animal model. In this
      study, we evaluated the genetic diversity for the breeding population,
      considering the years from 2003 to 2008. Only horses with at least one progeny
      during that time span were included. Results were obtained based on pedigree
      information as well as from molecular markers. A series of software packages were
      screened to combine best the best linear unbiased prediction (BLUP) methodology
      with optimal genetic contribution theory. We looked for stallions with highest
      breeding values and lowest average relationship to the dam population. Breeding
      with such stallions is expected to lead to a selection gain, while lowering the
      future increase in inbreeding within the breed.

PMID- 21906186
TI  - Sinus bone formation and implant survival after sinus membrane elevation and
      implant placement: a 1- to 6-year follow-up study.
AB  - OBJECTIVES: To investigate the long-term clinical and radiographic results of the
      maxillary sinus membrane elevation technique where implants were inserted in a
      void space created by the elevation of the sinus membrane without adding any
      graft material. MATERIALS AND METHODS: A total of 84 patients were subjected to
      96 membrane elevation procedures and simultaneous placement of 239 implants.
      Changes of intra-sinus and marginal bone height in relation to the implants were
      measured in intraoral radiographs taken at insertion, after 6 months of healing,
      after 6 months of loading and then annually. Computerized tomography was
      performed pre-surgically and 6 months post-surgically. Resonance Frequency
      Analyses measurements were performed at the time of implants placement, at
      abutment connection and after 6 months of loading. The implant follow-up period
      ranged from a minimum of one to a maximum of 6 years after implants loading.
      RESULTS: All implants were stable after 6 months of healing. A total of three
      implants were lost during the follow-up period giving a survival rate of 98.7%.
      Radiography demonstrated on average 5.3+/-2.1 mm of intra-sinus new bone
      formation after 6 months of healing. RFA measurements showed adequate primary
      stability (implant stability quotient 67.4+/-6.1) and small changes over time.
      CONCLUSION: Maxillary sinus membrane elevation and simultaneous placement of
      implants without the use of bone grafts or bone substitutes result in predictable
      bone formation with a high implant survival rate of 98.7% during a follow-up
      period of up to 6 years. The intra-sinus bone formation remained stable in the
      long-term follow-up. It is suggested that the secluded compartment allowed for
      bone formation according to the principle of guided tissue regeneration. The high
      implant survival rate of 98.7% indicated that the implants sufficiently supported
      the fixed bridges throughout the study period. This technique reduces the risks
      for morbidity related to harvesting of bone grafts and eliminates the costs of
      grafting materials.

PMID- 21906188
TI  - Cultivation with untransfected fibroblasts stimulates proliferation of a single
      gene-modified fibroblast derived from a clawn miniature swine foetus.
AB  - Porcine embryonic fibroblasts (PEFs) have been used extensively as donor nuclei
      for the production of cloned pigs via somatic cell nuclear transfer (SCNT).
      Somatic cell nuclear transfer of gene-targeted PEFs has been the only way to
      produce gene-targeted pigs, given the lack of germ-line-competent porcine
      embryonic stem cells. Unlike other primary-cultured cells, such as murine
      embryonic fibroblasts, a single porcine PEF is unable to proliferate under normal
      conditions in which a certain number of PEFs (likely over 100) can grow normally.
      This limitation greatly hampers re-cloning of gene-modified PEFs, which is
      required for SCNT. Herein, we demonstrate the cultivation of a single PEF
      transfectant carrying the pEGFP-N1 plasmid with intact normal PEFs (>100) in a
      Terasaki microtest plate, which resulted in stimulation of the growth of the
      former cell (doubling time = 2.6 days). In contrast, when a single cell was
      cultured, it could typically divide only once and never divided more than twice.
      When a single transfectant was seeded in a well of a 96-well plate together with
      5 * 10(4) untransfected PEFs and was subsequently selected in the presence of
      G418, we obtained a pure cell population of single-cell origin. Thus, this method
      should be useful for the purification of target recombinant pig clones from
      mosaic populations that cannot be cultured as a single cell or for which suitable
      cell growth-promoting conditions are unclear.

PMID- 21906189
TI  - Effect of a bacterial lipopolysaccharide treatment on rabbit testis and
      ejaculated sperm.
AB  - In a previous study, we reported the short- and long-term effects of bacterial
      lipopolysaccharide (LPS)-induced inflammation on rabbit sperm quality. This study
      was aimed at exploring the spermatogenesis of the rabbit model focussing on the
      possible damages occurring to the testis and ejaculated sperm. Twenty New Zealand
      White rabbit bucks were divided into two groups. One group was inoculated intra
      peritoneally with LPS, the other group, considered as control, was treated under
      the same conditions with saline only. Semen samples were collected before LPS
      injection, the 7th, 14th, 21st, 30th, 45th, 60th and 90th day after LPS
      treatment. Semen parameters were evaluated following international guidelines.
      The kinetic characteristics of ejaculated sperm were analysed using a computer
      assisted sperm analyzer and the ultrastructural characteristics were explored by
      transmission electron microscopy (TEM). On the 7th, 14th and 30th day, testis
      from treated rabbits and controls were obtained. Testis samples were analysed by
      light microscopy and TEM. The induced LPS lesions in the testis became evident
      the 7th day after treatment, with a decrease in germinal cells and with an
      increase in structurally altered Sertoli cells; normal spermatogenesis was
      restored on the 30th day. The testicular damages observed on day 7 were probably
      responsible for the reduction in sperm concentration and motility and the
      ultrastructural alterations that were detected in the ejaculated sperm on the
      14th through the 30th days after treatment. In conclusion, rabbit buck treated
      with LPS could be a useful model for studying the effect of an induced systemic
      inflammation on spermatogenesis.

PMID- 21906190
TI  - Gene expression differences in oocytes derived from adult and prepubertal
      Japanese Black cattle during in vitro maturation.
AB  - The present study was carried out to compare the gene expression profiles in
      oocytes derived from adult and prepubertal Japanese Black cattle during in vitro
      maturation (IVM) using microarray gene chips (Bovine genome array containing
      24,072 probe sets representing over 23,000 transcripts). Microarray experiments
      were conducted using total RNA isolated from immature [germinal vesicle (GV)] and
      in vitro matured [metaphase II, (MII)] oocytes derived from adult and prepubertal
      animals. A total of 333 (1.4%) and 549 (2.3%) genes were differentially expressed
      between prepubertal vs adult bovine GV and MII stages oocytes, respectively. Of
      these, 176 and 312 genes were up-regulated, while 157 and 237 were down-regulated
      in prepubertal when compared with adult GV and MII oocytes, respectively. It was
      also observed that 695 (2.9%) and 553 (2.3%) genes were differentially expressed
      between GV vs MII stage oocytes in the adult and prepubertal groups,
      respectively. Gene ontological classification of the differentially expressed
      genes revealed that up-regulated genes in adult oocytes were involved in signal
      transduction, transcriptional control and transport. Quantitative reverse
      transcription-PCR validated the expression profile of some selected transcripts
      and confirmed differences in the expression levels of transcripts between adult
      vs prepubertal groups in both GV and MII stages oocytes as identified by
      microarray data analysis. This study indicated for the first time that
      significant number of genes were differentially expressed (>2-fold, p < 0.01)
      between oocytes derived from adult and those from prepubertal Japanese Black
      cattle, and this difference increased during IVM.

PMID- 21906191
TI  - Routine antenatal anti-D prophylaxis--is the protection adequate?
AB  - BACKGROUND/AIMS: Prophylactic anti-D given during pregnancy can be detected in
      current indirect antiglobulin tests (IAT). Using this to measure the persistence
      of prophylactic anti-D, this study set out to determine whether there is an
      association between anti-D detectable at delivery and the RhD status of the
      foetus and/or the duration of the pregnancy post the standard 28 week dose of
      routine antenatal anti-D prophylaxis (RAADP). The study also investigated the
      detection rates of anti-D at delivery when given in a two dose regime or a one
      dose regime. METHOD: All IAT screening was undertaken using fully automated
      Diamed gel technology. The results from 407 women were included in the two dose
      regime study, and 157 in the one dose regime study. RESULTS: 160/407 (39%) women
      receiving one dose of prophylactic anti-D had no detectable anti-D at delivery.
      123/157 (78%) women on the one dose regime had no detectable anti-D at delivery.
      No association was found between detectable anti-D at delivery and the RhD status
      of the infant in either study arm. A strong association was found between
      detectable anti-D Ig at delivery and the duration of the pregnancy post the 28
      week dose in each study arm. CONCLUSION: Our data show that neither the two dose
      nor the one dose regime appear to provide adequate cover at delivery for a large
      percentage of pregnant women. This appears to be associated with the duration of
      the pregnancy past the 28 week dose but not associated with the RhD status of the
      foetus.

PMID- 21906192
TI  - Examining supply changes in Australia's cocaine market.
AB  - INTRODUCTION AND AIMS: Media attention to cocaine use and supply has increased
      following some of the largest cocaine seizures in Australia's history. Whether
      there has been an expansion in supply remains unclear. This paper examines the
      evidence behind assertions of increased supply in Australia and the scale and
      nature of any apparent increase, using proxy indicators of cocaine importation,
      distribution and use. DESIGN AND METHODS: Eight proxies of cocaine importation,
      distribution and use were adopted, including amount of importation, mode of
      importation and supply flows to Australia. Each proxy indicator was sourced using
      publicly available and Australia-wide data, including information on the total
      weight of border seizures, mode of detection and country of embarkation of
      individual seizures. Data permitting, trends were examined for up to a 12 year
      period (1997-1998 to 2009-2010). RESULTS: Since 2006-2007 there was evidence of
      increased cocaine importation, albeit less than between 1998-1999 and 2001-2002.
      There were further signs that the 2006-2007 expansion coincided with a
      diversification of trafficking routes to and through Australia (beyond the
      traditional site of entry-Sydney) and shifts in the geographic distribution of
      use. DISCUSSION AND CONCLUSIONS: The congruity between indicators suggests that
      there has been a recent expansion in cocaine supply to and distribution within
      Australia, but that the more notable shift has concerned the nature of supply,
      with an apparent growth in importation and distribution beyond New South Wales.
      The diversification of cocaine supply routes may increase risks of market
      entrenchment and organised crime throughout Australia.

PMID- 21906193
TI  - Biogenic amine receptor gene expression in the ovarian tissue of the honey bee
      Apis mellifera.
AB  - In the honey bee Apis mellifera loss of the queen from a colony induces increased
      levels of the biogenic amine dopamine in the brain of workers, and this elevation
      is correlated with ovary activation. In the present study we use real-time
      quantitative PCR to investigate expression of five biogenic amine receptor genes.
      We show that biogenic amine receptors are expressed in ovarian tissue, and that
      their expression is strongly influenced by the presence or absence of a queen in
      the colony. In contrast to the brain, where all three dopamine receptors are
      expressed, only two dopamine receptors are expressed in the ovaries, and their
      expression is strongly correlated with the reproductive status of workers. We
      conclude that biogenic amine receptors are expressed in the ovaries and are
      likely to be directly influential in the regulation of worker sterility in honey
      bees.

PMID- 21906194
TI  - Prolixicin: a novel antimicrobial peptide isolated from Rhodnius prolixus with
      differential activity against bacteria and Trypanosoma cruzi.
AB  - We identified and characterized the activity of prolixicin, a novel antimicrobial
      peptide (AMP) isolated from the hemipteran insect, Rhodnius prolixus. Sequence
      analysis reveals one region of prolixicin that may be related to the
      diptericin/attacin family of AMPs. Prolixicin is an 11-kDa peptide containing a
      putative 21 amino acid signal peptide, two putative phosphorylation sites and no
      glycosylation sites. It is produced by both adult fat body and midgut tissues in
      response to bacterial infection of the haemolymph or the midgut. Unlike most
      insect antibacterial peptides, the prolixicin gene does not seem to be regulated
      by NF-kappaB binding sites, but its promoter region contains several GATA sites.
      Recombinant prolixicin has strong activity against the Gram-negative bacterium
      Escherichia coli and differential activity against several Gram-negative and Gram
      positive bacteria. No significant toxicity was demonstrated against Trypanosoma
      cruzi, the human parasite transmitted by R. prolixus.

PMID- 21906195
TI  - An ancient icon reveals new mysteries: mummy DNA resurrects a cryptic species
      within the Nile crocodile.
AB  - The Nile crocodile (Crocodylus niloticus) is an ancient icon of both cultural and
      scientific interest. The species is emblematic of the great civilizations of the
      Nile River valley and serves as a model for international wildlife conservation.
      Despite its familiarity, a centuries-long dispute over the taxonomic status of
      the Nile crocodile remains unresolved. This dispute not only confounds our
      understanding of the origins and biogeography of the 'true crocodiles' of the
      crown genus Crocodylus, but also complicates conservation and management of this
      commercially valuable species. We have taken a total evidence approach involving
      phylogenetic analysis of mitochondrial and nuclear markers, as well as karyotype
      analysis of chromosome number and structure, to assess the monophyletic status of
      the Nile crocodile. Samples were collected from throughout Africa, covering all
      major bioregions. We also utilized specimens from museum collections, including
      mummified crocodiles from the ancient Egyptian temples at Thebes and the Grottes
      de Samoun, to reconstruct the genetic profiles of extirpated populations. Our
      analyses reveal a cryptic evolutionary lineage within the Nile crocodile that
      elucidates the biogeographic history of the genus and clarifies long-standing
      arguments over the species' taxonomic identity and conservation status. An
      examination of crocodile mummy haplotypes indicates that the cryptic lineage
      corresponds to an earlier description of C. suchus and suggests that both African
      Crocodylus lineages historically inhabited the Nile River. Recent survey efforts
      indicate that C. suchus is declining or extirpated throughout much of its
      distribution. Without proper recognition of this cryptic species, current
      sustainable use-based management policies for the Nile crocodile may do more harm
      than good. 

PMID- 21906196
TI  - What can we learn from the Dutch cannabis coffeeshop system?
AB  - AIMS: To examine the empirical consequences of officially tolerated retail sales
      of cannabis in the Netherlands, and possible implications for the legalization
      debate. METHODS: Available Dutch data on the prevalence and patterns of use,
      treatment, sanctioning, prices and purity for cannabis dating back to the 1970s
      are compared to similar indicators in Europe and the United States. RESULTS: The
      available evidence suggests that the prevalence of cannabis use among Dutch
      citizens rose and fell as the number of coffeeshops increased and later declined,
      but only modestly. The coffeeshops do not appear to encourage escalation into
      heavier use or lengthier using careers, although treatment rates for cannabis are
      higher than elsewhere in Europe. Scatterplot analyses suggest that Dutch patterns
      of use are very typical for Europe, and that the 'separation of markets' may
      indeed have somewhat weakened the link between cannabis use and the use of
      cocaine or amphetamines. CONCLUSIONS: Cannabis consumption in the Netherlands is
      lower than would be expected in an unrestricted market, perhaps because cannabis
      prices have remained high due to production-level prohibitions. The Dutch system
      serves as a nuanced alternative to both full prohibition and full legalization.

PMID- 21906197
TI  - The effect of tobacco control policies on smoking prevalence and smoking
      attributable deaths. Findings from the Netherlands SimSmoke Tobacco Control
      Policy Simulation Model.
AB  - AIM: To develop a simulation model projecting the effect of tobacco control
      policies in the Netherlands on smoking prevalence and smoking-attributable
      deaths. DESIGN, SETTING AND PARTICIPANTS: Netherlands SimSmoke-an adapted version
      of the SimSmoke simulation model of tobacco control policy-uses population,
      smoking rates and tobacco control policy data for the Netherlands to predict the
      effect of seven types of policies: taxes, smoke-free legislation, mass media,
      advertising bans, health warnings, cessation treatment and youth access policies.
      MEASUREMENTS: Outcome measures were smoking prevalence and smoking-attributable
      deaths. FINDINGS: With a comprehensive set of policies, as recommended by MPOWER,
      smoking prevalence can be decreased by as much as 21% in the first year,
      increasing to a 35% reduction in the next 20 years and almost 40% by 30 years. By
      2040, 7706 deaths can be averted in that year alone with the stronger set of
      policies. Without effective tobacco control policies, almost a million lives will
      be lost to tobacco-related diseases between 2011 and 2040. Of those, 145,000 can
      be saved with a comprehensive tobacco control package. CONCLUSIONS: Smoking
      prevalence and smoking-attributable deaths in the Netherlands can be reduced
      substantially through tax increases, smoke-free legislation, high-intensity media
      campaigns, stronger advertising bans and health warnings, comprehensive cessation
      treatment and youth access laws. The implementation of these FCTC/MPOWER
      recommended policies could be expected to show similar or even larger relative
      reductions in smoking prevalence in other countries which currently have weak
      policies.

PMID- 21906198
TI  - The impact of small changes in bar closing hours on violence. The Norwegian
      experience from 18 cities.
AB  - AIMS: To estimate the effect on violence of small changes in closing hours for on
      premise alcohol sales, and to assess whether a possible effect is symmetrical.
      DESIGN, SETTING, AND PARTICIPANTS: A quasi-experimental design drawing on data
      from 18 Norwegian cities that have changed (extended or restricted) the closing
      hours for on-premise alcohol sales. All changes were <= 2 hours. MEASUREMENTS:
      Closing hours were measured in terms of the latest permitted hour of on-premise
      trading, ranging from 1 a.m. to 3 a.m. The outcome measure comprised police
      reported assaults that occurred in the city centre between 10 p.m. and 5 a.m. at
      weekends. Assaults outside the city centre during the same time window should not
      be affected by changes in closing hours but function as a proxy for potential
      confounders, and was thus included as a control variable. The data spanned the
      period Q1 2000-Q3 2010, yielding 774 observations. FINDINGS: Outcomes from main
      analyses suggested that each 1-hour extension of closing hours was associated
      with a statistically significant increase of 4.8 assaults (95% CI 2.60, 6.99) per
      100,000 inhabitants per quarter (i.e. an increase of about 16%). Findings
      indicate that the effect is symmetrical. These findings were consistent across
      three different modelling techniques. CONCLUSION: In Norway, each additional 1
      hour extension to the opening times of premises selling alcohol is associated
      with a 16% increase in violent crime.

PMID- 21906199
TI  - Delay discounting by adolescents experimenting with cigarette smoking.
AB  - AIMS: To evaluate delay discounting and self-reported impulsive behavior in a
      sample of adolescents experimenting with cigarette smoking compared with
      adolescents who had never smoked or were daily smokers. DESIGN: A cross-sectional
      design was used to compare smoking-status groups. SETTING: Columbus, Ohio, a city
      of approximately 780,000 people. PARTICIPANTS: A sample of 141 male and female
      adolescents with a mean age of 15.37 (standard deviation = 1.09) years.
      MEASUREMENTS: Primary measures included a computerized assessment of delay
      discounting, a self-report assessment of impulsivity [Barratt Impulsiveness Scale
      adolescent (BIS-11-A)] and verifications of cigarette smoking status (breath
      carbon monoxide and urinary cotinine level). FINDINGS: Smokers discounted more by
      delay and had higher impulsivity scores than non-smokers. Experimenters had
      scores intermediate to those of smokers and non-smokers on both measures. In some
      analyses the difference between experimenters and non-smokers was significant,
      with experimenters showing greater delay discounting, but in no case did
      experimenters differ significantly from the smokers. CONCLUSIONS: Young people
      who experiment with cigarettes appear to be similar to those who smoke regularly
      in terms of tendency to discount future gains and report impulsive tendencies,
      and generally higher in these traits than non-smokers.

PMID- 21906201
TI  - Comparison of serial qualitative and quantitative assessments of caval index and
      left ventricular systolic function during early fluid resuscitation of
      hypotensive emergency department patients.
AB  - OBJECTIVES: The objective was to determine whether serial bedside visual
      estimates of left ventricular systolic function (LVF) and respiratory variation
      of the inferior vena cava (IVC) diameter would agree with quantitative
      measurements of LVF and caval index in hypotensive emergency department (ED)
      patients during fluid challenges. The authors hypothesized that there would be
      moderate inter-rater agreement on the visual estimates. METHODS: This prospective
      observational study was performed at an urban, regional ED. Patients were
      eligible for enrollment if they were hypotensive in the ED as defined by a
      systolic blood pressure (sBP) of <100 mm Hg or mean arterial pressure of <=65 mm
      Hg, exhibited signs or symptoms of shock, and the treating physician intended to
      administer intravenous (IV) fluid boluses for resuscitation. Sonologists
      performed a sequence of echocardiographic assessments at the beginning, during,
      and toward the end of fluid challenge. Both caval index and LVF were determined
      by the sonologist in qualitative then quantitative manners. Deidentified digital
      video clips of two-dimensional IVC and LVF assessments were later presented, in
      random order, to an ultrasound (US) fellowship-trained emergency physician using
      a standardized rating system for review. Statistical analysis included both
      descriptive statistics and correlation analysis. RESULTS: Twenty-four patients
      were enrolled and yielded 72 caval index and LVF videos that were scored at the
      bedside prior to any measurements and then reviewed later. Visual estimates of
      caval index compared to measured caval index yielded a correlation of 0.81 (p <
      0.0001). Visual estimates of LVF compared to fractional shortening yielded a
      correlation of 0.84 (p < 0.0001). Inter-rater agreement of respiratory variation
      of IVC diameter and LVF scores had simple kappa values of 0.70 (95% confidence
      interval [CI] = 0.56 to 0.85) and 0.46 (95% CI = 0.29 to 0.63), respectively.
      Significant differences in mean values between time 0 and time 2 were found for
      caval index measurements, the visual scores of IVC diameter variation, and both
      maximum and minimum IVC diameters. CONCLUSIONS: This study showed that serial
      visual estimations of the respiratory variation of IVC diameter and LVF agreed
      with bedside measurements of caval index and LVF during early fluid challenges to
      symptomatic hypotensive ED patients. There was moderate inter-rater agreement in
      both visual estimates. In addition, acute volume loading was associated with
      detectable acute changes in IVC measurements.

PMID- 21906200
TI  - Drug use in rural China: a preliminary investigation in Hunan Province.
AB  - AIMS: To compare characteristics and illicit drug abuse patterns among drug
      abusers in rural and urban areas of Hunan Province, China. MEASUREMENTS AND
      DESIGN: Data collected by public security bureau on newly registered drug abusers
      between 2005 and 2008 in five urban and five rural areas (n = 1639) were
      extracted anonymously and analyzed. SETTING AND PARTICIPANTS: All newly
      registered drug users in urban (n = 812) and rural (n = 827) areas of Hunan
      Province were included. FINDINGS: Drug users from the rural areas were younger
      [31 (6.6) versus 34 (8.0) years, P < 0.001], with a higher proportion of males
      (86% versus 82%, P < 0.05) or married (34% versus 27%, P < 0.01). Rural drug
      users reported an earlier onset of drug use [27 (5.9) versus 30 (7.9) years old,
      P < 0.001], were more likely to report heroin as their primary drug of abuse (53%
      versus 47%, P < 0.001) and had a lower prevalence of criminal activities (19%
      versus 31%, P < 0.001). Rural drug users were less likely to report needle
      sharing (1.8% versus 4.3%, P < 0.01), less likely to report being human
      immunodeficiency virus positive (0.8% versus 2.6%, P < 0.01) and less likely to
      report prior drug treatment participation (2.8% versus 6.8%, P < 0.001).
      CONCLUSIONS: Drug abuse is a substantial problem in both urban and rural areas in
      China. The very low proportion of newly registered drug users reporting any prior
      drug abuse treatment points to the importance of expanding substance abuse
      treatments, especially in rural areas where treatment penetration is even lower
      than in urban areas.

PMID- 21906202
TI  - Feasibility of nonmydriatic ocular fundus photography in the emergency
      department: Phase I of the FOTO-ED study.
AB  - OBJECTIVES: Examination of the ocular fundus is imperative in many acute medical
      and neurologic conditions, but direct ophthalmoscopy by nonophthalmologists is
      underutilized, poorly performed, and difficult without pharmacologic pupillary
      dilation. The objective was to examine the feasibility of nonmydriatic fundus
      photography as a clinical alternative to direct ophthalmoscopy by emergency
      physicians (EPs). METHODS: Adult patients presenting to the emergency department
      (ED) with headache, acute focal neurologic deficit, diastolic blood pressure >=
      120 mm Hg, or acute visual change had ocular fundus photographs taken by nurse
      practitioners using a nonmydriatic fundus camera. Photographs were reviewed by a
      neuroophthalmologist within 24 hours for findings relevant to acute ED patient
      care. Nurse practitioners and patients rated ease, comfort, and speed of
      nonmydriatic fundus photography on a 10-point Likert scale (10 best). Timing of
      visit and photography were recorded by automated electronic systems. RESULTS: A
      total of 350 patients were enrolled. There were 1,734 photographs taken during
      230 nurse practitioner shifts. Eighty-three percent of the 350 patients had at
      least one eye with a high-quality photograph, while only 3% of patients had no
      photographs of diagnostic value. Mean ratings were >= 8.7 (standard deviation
      [SD] <= 1.9) for all measures. The median photography session lasted 1.9 minutes
      (interquartile range [IQR] = 1.3 to 2.9 minutes), typically accounting for less
      that 0.5% of the patient's total ED visit. CONCLUSIONS: Nonmydriatic fundus
      photography taken by nurse practitioners is a feasible alternative to direct
      ophthalmoscopy in the ED. It is performed well by nonphysician staff, is well
      received by staff and patients, and requires a trivial amount of time to perform.

PMID- 21906203
TI  - Variations in crowding and ambulance diversion in nine emergency departments.
AB  - OBJECTIVES: The primary study aim was to examine the variations in crowding when
      an emergency department (ED) initiates ambulance diversion. METHODS: This
      retrospective, multicenter study included nine geographically disparate EDs.
      Daily ED operational variables were collected during a 12-month period (January
      2009 to December 2009), including total number of ED visits, mean overall length
      of stay (LOS), number of ED beds, and hours on ambulance diversion. The primary
      outcome variable was the "ED workload rate," a surrogate marker for daily ED
      crowding. It was calculated as the total number of daily ED visits multiplied by
      the overall mean LOS (in hours) and divided by the number of ED beds available
      for acute treatment in a given day. The primary predictor variables were
      ambulance diversion, as a dichotomous variable of whether or not an ED went on
      diversion at least once during a 24-hour period, diversion hour quintiles, and
      sites. RESULTS: The annual ED census ranged from 43,000 to 101,000 patients. The
      percentage of days that an ED went on diversion at least once varied from 4.9% to
      86.6%. On days with ambulance diversion, the mean ED workload rate varied from
      17.1 to 62.1 patient LOS hours per ED bed among sites. The magnitude of variation
      in ED workload rate was similar on days without ambulance diversion. Differences
      in ED workload rate varied among sites, ranging from 1.0 to 6.0 patient LOS hours
      per ED bed. ED workload rate was higher on average on diversion days compared to
      nondiversion days. The mean difference between diversion and nondiversion was
      statistically significant for the majority of sites. CONCLUSIONS: There was
      marked variation in ED workload rates and whether or not ambulance diversion
      occurred during a 24-hour period. This variability in initiating ambulance
      diversion suggests different or inconsistently applied decision-making criteria
      for initiating diversion.

PMID- 21906204
TI  - Short-term mortality risk in emergency department acute heart failure.
AB  - OBJECTIVES: Few tools exist that provide objective accurate prediction of short
      term mortality risk in patients presenting with acute heart failure (AHF). The
      purpose was to describe the accuracy of several biomarkers for predicting short
      term death rates in patients diagnosed with AHF in the emergency department (ED).
      METHODS: The Biomarkers in ACute Heart failure (BACH) trial was a prospective, 15
      center, international study of patients presenting to the ED with nontraumatic
      dyspnea. Clinicians were blinded to all investigational markers, except troponin
      and natriuretic peptides, which used the local hospital reference range. For this
      secondary analysis, a core lab was used for all markers except troponin. This
      study evaluated patients diagnosed with AHF by the on-site emergency physician
      (EP). RESULTS: In the 1,641 BACH patients, 466 (28.4%) had an ED diagnosis of
      AHF, of whom 411 (88.2%) had a final diagnosis of AHF. In the ED-diagnosed HF
      patients, 59% were male, 69% had a HF history, and 19 (4.1%) died within 14 days
      of their ED visit. The area under the curve (AUC) for the 14-day mortality
      receiver operating characteristic (ROC) curve was 0.484 for brain natriuretic
      peptide (BNP), 0.586 for N-terminal pro-B-type natriuretic peptide (NT-proBNP),
      0.755 for troponin (I or T), 0.742 for adrenomedullin (MR-proADM), and 0.803 for
      copeptin. In combination, MR-proADM and copeptin had the best 14-day mortality
      prediction (AUC = 0.818), versus all other markers. CONCLUSIONS: MR-proADM and
      copeptin, alone or in combination, may provide superior short-term mortality
      prediction compared to natriuretic peptides and troponin. Presented results are
      explorative due to the limited number of events, but validation in larger trials
      seems promising.

PMID- 21906205
TI  - Risk adjustment measures and outcome measures for prehospital trauma research:
      recommendations from the emergency medical services outcomes project (EMSOP).
AB  - OBJECTIVES: The objectives were to conduct a comprehensive, systematic review of
      the literature for risk adjustment measures (RAMs) and outcome measures (OMs) for
      prehospital trauma research and to use a structured expert panel process to
      recommend measures for use in future emergency medical services (EMS) trauma
      outcomes research. METHODS: A systematic literature search and review was
      performed identifying the published studies evaluating RAMs and OMs for
      prehospital injury research. An explicit structured review of all articles
      pertaining to each measure was conducted using the previously established
      methodology developed by the Canadian Physiotherapy Association ("Physical
      Rehabilitation Outcome Measures"). RESULTS: Among the 4,885 articles reviewed, 96
      RAMs and/or OMs were identified from the existing literature (January 1958 to
      February 2010). Only one measure, the Glasgow Coma Scale (GCS), currently meets
      Level 1 quality of evidence status and a Category 1 (strong) recommendation for
      use in EMS trauma research. Twelve RAMs or OMs received Category 2 status
      (promising, but not sufficient current evidence to strongly recommend), including
      the motor component of GCS, simplified motor score (SMS), the simplified verbal
      score (SVS), the revised trauma score (RTS), the prehospital index (PHI), EMS
      provider judgment, the revised trauma index (RTI), the rapid acute physiology
      score (RAPS), the rapid emergency medicine score (REMS), the field trauma triage
      (FTT), the pediatric triage rule, and the out-of-hospital decision rule for
      pediatrics. CONCLUSIONS: Using a previously published process, a structured
      literature review, and consensus expert panel opinion, only the GCS can currently
      be firmly recommended as a specific RAM or OM for prehospital trauma research
      (along with core measures that have already been established and published). This
      effort highlights the paucity of reliable, validated RAMs and OMs currently
      available for outcomes research in the prehospital setting and hopefully will
      encourage additional, methodologically sound evaluations of the promising,
      Category 2 RAMs and OMs, as well as the development of new measures.

PMID- 21906206
TI  - ACR appropriateness criteria(r) locally advanced breast cancer.
AB  - Locally advanced breast cancer (LABC) is a disease that is heterogeneous in its
      presentation, potentially curable, and generally necessitating multidisciplinary
      management. Radiation therapy (RT) plays an important role in the management of
      LABC. The integration of radiation with surgery, chemotherapy, and sometimes
      breast reconstruction can be complex. The American College of Radiology
      Appropriateness Criteria Breast Committee aims to provide guidance for the
      management of a variety of LABC cases. The American College of Radiology
      Appropriateness Criteria is evidence-based guidelines for specific clinical
      conditions that are reviewed every 2 years by a multidisciplinary expert panel.
      The guideline development and review include an extensive analysis of current
      medical literature from peer-reviewed journals and the application of a well
      established consensus methodology (modified Delphi) to rate the appropriateness
      of imaging and treatment procedures by the panel. In those instances where
      evidence is either lacking or not definitive, expert opinion may be used to
      recommend imaging or treatment.

PMID- 21906207
TI  - Calcifications in the breast and digital breast tomosynthesis.
AB  - Our study was to compare the clarity with which calcifications are seen on
      conventional mammography (CM) with the same calcifications on digital breast
      tomosynthesis (DBT). We define clarity as the sharpness, contrast, and diagnostic
      quality by which the calcifications were depicted. In a HIPPA compliant
      Institutional Review Board approved study, 3,000 women volunteered to have both a
      screening mammogram and a DBT study. A total of 119 sequential cases with
      relevant calcifications (not clearly benign) were reviewed. Two board certified,
      dedicated, breast imaging radiologists reviewed the CM and DBT images in an
      unblinded paired comparison. Only the mediolateral oblique (MLO) projection was
      available for the DBT studies. The MLO and craniocaudal projections were reviewed
      using the 2D images. Window and leveling, and electronic zoom were permitted.
      Unlimited time was allowed to provide a subjective assessment as too how well the
      calcifications were seen, from a diagnostic perspective, when the two studies
      were evaluated side-by-side. In 41.6% of the cases, the readers felt that
      calcifications were seen with superior clarity on DBT. In 50.4% of the cases, the
      visibility of calcifications was the same for DBT and CM, and in 8% of the cases,
      calcifications were seen with greater clarity on CM than DBT. In 92% of the
      cases, the clarity with which calcifications were seen on DBT was equal to or
      better than for CM and in almost half, the clarity on DBT was judged to be better
      than for CM. Our analysis shows that calcifications can be demonstrated with
      equal or greater clarity on DBT as on CM, thus allowing for comparable, and,
      perhaps, improved interpretive analysis of detected calcifications.

PMID- 21906208
TI  - Radioactive seed localization of breast lesions: an adequate localization method
      without seed migration.
AB  - Preoperative localization is important to optimize the surgical treatment of
      breast lesions, especially in nonpalpable lesions. Radioactive seed localization
      (RSL) using iodine-125 is a relatively new approach. To provide accurate guidance
      to surgery, it is important that the seeds do not migrate after placement. The
      aim of this study was to assess short-term and long-term seed migration after RSL
      of breast lesions. In 45 patients, 48 RSL procedures were performed under
      ultrasound or stereotactic guidance. In the first 12 patients, the lesion was
      localized with two markers: an iodine-125 seed and a reference marker. In 33
      patients, 36 RSL procedures were performed using a single iodine-125 seed. All
      patients received control mammograms after seed placement and prior to surgery.
      In the patients with two markers, migration was defined as the difference in the
      largest distance between the markers observed in the mammograms. For single
      marked lesions, migration was assessed by comparing distances between anatomical
      landmarks in the mammograms. RSL was successful in all patients. Seeds were in
      situ for 59.5 days on average (3-136 days). The detection rate during surgery was
      100%. Overall, an average seed migration of 0.9 mm (standard deviation 1.0 mm)
      was observed. Neither differences in lesion type, nor days in situ, type of
      surgery or radiologic localization method were found to have impact on seed
      migration. RSL is an accurate preoperative localization method for breast lesions
      with negligible seed migration, independent of time in-situ.

PMID- 21906209
TI  - Malignant seeding following percutaneous breast biopsy: documentation with
      comprehensive imaging and clinical implications.
AB  - The aim of this study was to demonstrate convincing evidence that percutaneous
      breast biopsy may result in displacement of malignant cells that can initiate
      tumor growth at a separate anatomic site, other than the index lesion. Two
      patients with malignancy diagnosed by percutaneous breast biopsy were followed up
      with subsequent imaging. The observation of displaced cells initiating subsequent
      malignant growth was compared retrospectively with the previous year's outcomes
      following percutaneous breast biopsy. Two cases of displaced malignant cells
      resulting in malignant growth at a separate site along the biopsy needle track
      were demonstrated by imaging. During the preceding year, 1644 biopsies with 298
      malignant results were compared with the outcomes of these two patients,
      resulting in a 0.7% incidence of malignant seeding. No identifiable factors could
      be identified to predict under what conditions this iatrogenic complication
      occurs. Although uncommon, percutaneous breast biopsy can result in malignant
      seeding, and raises issues regarding informed consent and proper subsequent
      treatment.

PMID- 21906210
TI  - Impact of triplicate testing on HIV genotypic tropism prediction in routine
      clinical practice.
AB  - Guidelines state that the CCR5-inhibitor Maraviroc should be prescribed to
      patients infected with R5-tropic HIV-1 only. Therefore, viral tropism needs to be
      assessed phenotypically or genotypically. Preliminary clinical trial data suggest
      that genotypic analysis in triplicate is associated with improved prediction of
      virological response by increasing the detection of X4-tropic variants. Our
      objective was to evaluate the impact of triplicate genotypic analysis on
      prediction of co-receptor usage in routine clinical practice. Samples from
      therapy-naive and therapy-experienced patients were collected for routine tropism
      testing at three European clinical centres. Viral RNA was isolated from plasma
      and proviral DNA from peripheral blood mononuclear cells. Gp120-V3 was amplified
      in a triplicate nested RT-PCR procedure and sequenced. Co-receptor usage was
      predicted using the Geno2Pheno([coreceptor]) algorithm and analysed with a false
      positive rate (FPR) of 5.75%, 10%, or an FPR of 20% and according to the current
      European guidelines on the clinical management of HIV-1 tropism testing. A total
      of 266 sequences were obtained from 101 patient samples. Discordance in tropism
      prediction for the triplicates was observed in ten samples using an FPR of 10%.
      Triplicate testing resulted in a 16.7% increase in X4-predicted samples and to
      reclassification from R5 to X4 tropism for four cases rendering these patients
      ineligible for Maraviroc treatment. In conclusion, triplicate genotypic tropism
      testing increases X4 tropism detection in individual cases, which may prove to be
      pivotal when CCR5-inhibitor therapy is applied.

PMID- 21906211
TI  - Nystagmus and oscillopsia.
AB  - The ocular motor system consists of several subsystems, including the vestibular
      ocular nystagmus saccade system, the pursuit system, the fixation and gaze
      holding system and the vergence system. All these subsystems aid the
      stabilization of the images on the retina during eye and head movements and any
      kind of disturbance of one of the systems can cause instability of the eyes (e.g.
      nystagmus) or an inadequate eye movement causing a mismatch between head and eye
      movement (e.g. bilateral vestibular failure). In both situations, the subjects
      experience a movement of the world (oscillopsia) which is quite disturbing. New
      insights into the patho-physiology of some of the ocular motor disorders have
      helped to establish new treatment options, in particular in downbeat nystagmus,
      upbeat nystagmus, periodic alternating nystagmus, acquired pendular nystagmus and
      paroxysmal vestibular episodes/attacks. The discussed patho-physiology of these
      disorders and the current literature on treatment options are discussed and
      practical treatment recommendations are given in the paper.

PMID- 21906212
TI  - Incidence of childhood and adolescence epilepsy: a community-based prospective
      study in the province of Ferrara and in Copparo, Italy, 1996-2005.
AB  - BACKGROUND: The annual incidence of childhood and adolescence epilepsy ranges
      from 41 to 97 diagnoses per 100,000 people in western Countries, with a reported
      decline over time. We aimed at studying the incidence of epilepsy in children and
      adolescents (1 month to 14 years) and its temporal trend in the province of
      Ferrara, northern Italy. METHODS: We implemented a community-based prospective
      multi-source registry. All children with newly diagnosed epilepsy in the period
      1996-2005 were recorded. RESULTS: The incidence rate of newly diagnosed epilepsy
      in the considered age range was 57 per 100,000 person-years, (95% CI: 49.3-65.9),
      with a peak in the first year of life (109.4; 95% CI: 69.4-164.1), without
      differences between the two gender. The estimates were significantly lower than
      those observed previously (97.3; 95% CI: 81.9-115.7). CONCLUSIONS: Incidence
      rates for epilepsy in the Italian population aged 1 month to 14 years are in line
      with those of other European and Northern American Countries. The incidence of
      childhood epilepsy has declined over time in our area. A reduced impact of
      serious perinatal adverse events could partly explain the decline.

PMID- 21906213
TI  - Iron content of Cambodian foods when prepared in cooking pots containing an iron
      ingot.
AB  - OBJECTIVES: To investigate the effect of cooking with an iron ingot on the iron
      content of several water and Cambodian food preparations. METHODS: Various food
      and water samples were prepared, in replicate, in glass and aluminium pots with
      and without an iron ingot. The samples were subjected to iron content analysis
      using standard ICP-OES procedures. RESULTS: Prepared with an ingot, the iron
      content was 76.3 MUg iron/g higher in lemon water, 32.6 MUg iron/g higher in pork
      soup and 3.3 MUg iron/g higher in fish soup, than in the same foods prepared
      without an ingot. Acidity of the food samples was positively associated with iron
      leaching. CONCLUSIONS: Even when taking into account the low bioavailability of
      contaminant iron, approximately 75% of the daily iron requirement can be met by
      consuming 1L of lemon water prepared with an iron ingot. Its use may be a cheap
      and sustainable means of improving iron intake for those with iron-deficient
      diets.

PMID- 21906214
TI  - Anal cleansing practices and faecal contamination: a preliminary investigation of
      behaviours and conditions in schools in rural Nyanza Province, Kenya.
AB  - OBJECTIVE: To learn how children in rural schools in Nyando District, Kenya clean
      themselves after defecation. METHODS: Six focus group discussions were held with
      boys and girls ages 12-15 in three rural schools in mid-2009. Parents were
      interviewed in one setting. In early 2010, a survey of head teachers was
      conducted in 114 schools in Nyanza Province, Kenya, to assess the provision of
      anal cleansing materials and handwashing water and soap in schools. RESULTS: Anal
      cleansing behaviour is linked with access to materials, age, social pressure,
      perceived personal risk of illness and emotional factors. Materials used for anal
      cleansing include schoolbook paper, leaves, grasses, stones, corncobs and one's
      own hands. Students have knowledge gaps in terms of personal hygiene. They were
      forthcoming with information on their anal cleansing practices. Almost no schools
      budgeted for or provided anal cleansing materials regularly. CONCLUSION: Anal
      cleansing is a necessary human activity. However, because of social taboos, there
      are few articles on the topic. School health plans overlook it as well.
      Researchers need to determine if and how current practices could harm child
      health to inform policy.

PMID- 21906215
TI  - First provincial survey of Angiostrongylus cantonensis in Guangdong Province,
      China.
AB  - The rat lungworm Angiostrongylus cantonensis is a zoonotic nematode with a wide
      distribution. We report the first provincial survey of the prevalence of A.
      cantonensis infection among wild rodents and snails in Guangdong Province, China.
      A total of 2929 Pomacea canaliculata and 1354 Achatina fulica were collected from
      fields in 22 survey sites with a larval infection rates ranging from 0-26.6% to 0
      45.4%. In addition, 114 Cipangopaludina sp and 252 Bellamya sp were bought from
      markets; larvae were found only in Bellamya snails from two survey sites with an
      infection rate of 1.4% (1/70) and 3.3% (3/91), respectively. Four hundred and
      ninety-one rodents were captured in nine sites (Rattus norvegicus, R.
      flavipectus, Suncus murinus, Mus musculus, Bandicota indica, R. losea and R.
      rattus). Adult worms were found in R. norvegicus, R. flavipectus and Bandicota
      indica. Our survey revealed a wide distribution of A. cantonensis and its
      intermediate hosts P. canaliculata and A. fulica in Guangdong. The prevalence of
      A. cantonensis in wild snails and rats poses a substantial risk for
      angiostrongyliasis in humans.

PMID- 21906216
TI  - Costs of dengue prevention and incremental cost of dengue outbreak control in
      Guantanamo, Cuba.
AB  - OBJECTIVE: To assess the economic cost of routine Aedes aegypti control in an at
      risk environment without dengue endemicity and the incremental costs incurred
      during a sporadic outbreak. METHODS: The study was conducted in 2006 in the city
      of Guantanamo, Cuba. We took a societal perspective to calculate costs in months
      without dengue transmission (January-July) and during an outbreak (August
      December). Data sources were bookkeeping records, direct observations and
      interviews. RESULTS: The total economic cost per inhabitant (p.i.) per month.
      (p.m.) increased from 2.76 USD in months without dengue transmission to 6.05 USD
      during an outbreak. In months without transmission, the routine Aedes control
      programme cost 1.67 USD p.i. p.m. Incremental costs during the outbreak were
      mainly incurred by the population and the primary/secondary level of the
      healthcare system, hardly by the vector control programme (1.64, 1.44 and 0.21
      UDS increment p.i. p.m., respectively). The total cost for managing a
      hospitalized suspected dengue case was 296.60 USD (62.0% direct medical, 9.0%
      direct non-medical and 29.0% indirect costs). In both periods, the main cost
      drivers for the Aedes control programme, the healthcare system and the community
      were the value of personnel and volunteer time or productivity losses.
      CONCLUSIONS: Intensive efforts to keep A. aegypti infestation low entail
      important economic costs for society. When a dengue outbreak does occur
      eventually, costs increase sharply. In-depth studies should assess which mix of
      activities and actors could maximize the effectiveness and cost-effectiveness of
      routine Aedes control and dengue prevention.

PMID- 21906217
TI  - Growth dependence of conjugation explains limited plasmid invasion in biofilms:
      an individual-based modelling study.
AB  - Plasmid invasion in biofilms is often surprisingly limited in spite of the close
      contact of cells in a biofilm. We hypothesized that this poor plasmid spread into
      deeper biofilm layers is caused by a dependence of conjugation on the growth rate
      (relative to the maximum growth rate) of the donor. By extending an individual
      based model of microbial growth and interactions to include the dynamics of
      plasmid carriage and transfer by individual cells, we were able to conduct in
      silico tests of this and other hypotheses on the dynamics of conjugal plasmid
      transfer in biofilms. For a generic model plasmid, we find that invasion of a
      resident biofilm is indeed limited when plasmid transfer depends on growth, but
      not so in the absence of growth dependence. Using sensitivity analysis we also
      find that parameters related to timing (i.e. a lag before the transconjugant can
      transfer, transfer proficiency and scan speed) and spatial reach (EPS yield,
      conjugal pilus length) are more important for successful plasmid invasion than
      the recipients' growth rate or the probability of segregational loss. While this
      study identifies one factor that can limit plasmid invasion in biofilms, the new
      individual-based framework introduced in this work is a powerful tool that
      enables one to test additional hypotheses on the spread and role of plasmids in
      microbial biofilms.

PMID- 21906219
TI  - Characterization of the rumen microbiota of pre-ruminant calves using metagenomic
      tools.
AB  - The temporal sequence of microbial establishment in the rumen of the neonatal
      ruminant has important ecological and pathophysiological implications. In this
      study, we characterized the rumen microbiota of pre-ruminant calves fed milk
      replacer using two approaches, pyrosequencing of hypervariable V3-V5 regions of
      the 16S rRNA gene and whole-genome shotgun approach. Fifteen bacterial phyla were
      identified in the microbiota of pre-ruminant calves. Bacteroidetes was the
      predominant phylum in the rumen microbiota of 42-day-old calves, representing
      74.8% of the 16S sequences, followed by Firmicutes (12.0%), Proteobacteria
      (10.4%), Verrucomicrobia (1.2%) and Synergistetes (1.1%). However, the phylum
      level composition of 14-day-old calves was distinctly different. A total of 170
      bacterial genera were identified while the core microbiome of pre-ruminant calves
      included 45 genera. Rumen development seemingly had a significant impact on
      microbial diversity. The dazzling functional diversity of the rumen microbiota
      was reflected by identification of 8298 Pfam and 3670 COG protein families. The
      rumen microbiota of pre-ruminant calves displayed a considerable compositional
      heterogeneity during early development. This is evidenced by a profound
      difference in rumen microbial composition between the two age groups. However,
      all functional classes between the two age groups had a remarkably similar
      assignment, suggesting that rumen microbial communities of pre-ruminant calves
      maintained a stable function and metabolic potentials while their phylogenetic
      composition fluctuated greatly. The presence of all major types of rumen
      microorganisms suggests that the rumen of pre-ruminant calves may not be
      rudimentary. Our results provide insight into rumen microbiota dynamics and will
      facilitate efforts in formulating optimal early-weaning strategies.

PMID- 21906221
TI  - PecS is an important player in the regulatory network governing the coordinated
      expression of virulence genes during the interaction between Dickeya dadantii
      3937 and plants.
AB  - Successful infection of a pathogen relies on the coordinated expression of
      numerous virulence factor-encoding genes. In plant-bacteria interactions, this
      control is very often achieved through the integration of several regulatory
      circuits controlling cell-cell communication or sensing environmental conditions.
      Dickeya dadantii (formerly Erwinia chrysanthemi), the causal agent of soft rot on
      many crops and ornamentals, provokes maceration of infected plants mainly by
      producing and secreting a battery of plant cell wall-degrading enzymes. However,
      several other virulence factors have also been characterized. During Arabidopsis
      infection, most D. dadantii virulence gene transcripts accumulated in a
      coordinated manner during infection. This activation requires a functional GacA
      GacS two-component regulatory system but the Gac system is not involved in the
      growth phase dependence of virulence gene expression. Here we show that, contrary
      to Pectobacterium, the AHL-mediated ExpIR quorum-sensing system does not play a
      major role in the growth phase-dependent control of D. dadantii virulence genes.
      On the other hand, the global regulator PecS participates in this coordinated
      expression since, in a pecS mutant, an early activation of virulence genes is
      observed both in vitro and in planta. This correlated with the known
      hypervirulence phenotype of the pecS mutant. Analysis of the relationship between
      the regulatory circuits governed by the PecS and GacA global regulators indicates
      that these two regulators act independently. PecS prevents a premature expression
      of virulence genes in the first stages of colonization whereas GacA, presumably
      in conjunction with other regulators, is required for the activation of virulence
      genes at the onset of symptom occurrence.

PMID- 21906224
TI  - Beyond the oral microbiome.
AB  - The human oral microbiome currently comprises 600-700 taxa, but estimates suggest
      that overall species numbers may turn out to be higher (~1200). Within the oral
      cavity, groups of microbial species become arranged into surface-localized
      communities that vary considerably in composition according to sites of
      establishment. Factors such as nutrient availability, pH, toxic metabolites,
      shear forces and host conditions contribute to modelling the structure and
      activities of these oral microbial communities. With development of more rapid
      and accurate molecular techniques it has become possible to begin to characterize
      the genome contents of individual communities. However, understanding the
      phenotypic interactions between cultivable microorganisms within communities is
      essential in order to complement the genomic data. This will then enable
      construction of microbial community interactomes, incorporating genomic and
      spatial information with functional knowledge of physical and metabolic
      interplays between the microorganisms. Enlightenment of the changes in genome
      composition and phenotypic interactions as functions of niche, time and
      intrusions will help towards developing better means of manipulating communities
      for host benefit.

PMID- 21906223
TI  - The role of reduction in iron uptake processes in a unicellular, planktonic
      cyanobacterium.
AB  - In many aquatic environments the essential micronutrient iron is predominantly
      complexed by a heterogeneous pool of strong organic chelators. Research on iron
      uptake mechanisms of cyanobacteria inhabiting these environments has focused on
      endogenous siderophore production and internalization. However, as many
      cyanobacterial species do not produce siderophores, alternative Fe acquisition
      mechanisms must exist. Here we present a study of the iron uptake pathways in the
      unicellular, planktonic, non-siderophore producing strain Synechocystis sp. PCC
      6803. By applying trace metal clean techniques and a chemically controlled growth
      medium we obtained reliable and reproducible short-term (radioactive assays) and
      long-term (growth experiments) iron uptake rates. We found that Synechocystis
      6803 is capable of acquiring iron from exogenous ferrisiderophores (Ferrioxamine
      B, FeAerobactin) and that unchelated, inorganic Fe is a highly available source
      of iron. Inhibition of iron uptake by the Fe(II)-specific ligand, ferrozine,
      indicated that reduction of both inorganic iron and ferrisiderophore complexes
      occurs before transport through the plasma membrane. Measurements of iron
      reduction rates and the inhibitory effect of ferrozine on growth supported this
      conclusion. The reduction-based uptake strategy is well suited for acquiring iron
      from multiple complexes in dilute aquatic environments and may play an important
      role in other cyanobacterial strains.

PMID- 21906225
TI  - Human distal gut microbiome.
AB  - The distal gut and its associated microbiota is a new frontier in the quest to
      understand human biology and evolution. The renaissance in this field has been
      partly driven by advances in sequencing technology and also by the application of
      a variety of 'omic' technologies in a systems biology framework. In the initial
      stages of understanding what constitutes the gut, culture-independent methods,
      primarily inventories of 16S rRNA genes, have provided a clear view of the main
      taxonomic groups of Bacteria in the distal gut and we are now moving towards
      defining the functions that reside in the distal gut microbiome. This review will
      explore recent advances in the area of the distal gut and the use of a variety of
      omic approaches to determine what constitutes this fascinating collection of
      microbes.

PMID- 21906222
TI  - Effects of ocean acidification on microbial community composition of, and oxygen
      fluxes through, biofilms from the Great Barrier Reef.
AB  - Rising anthropogenic CO(2) emissions acidify the oceans, and cause changes to
      seawater carbon chemistry. Bacterial biofilm communities reflect environmental
      disturbances and may rapidly respond to ocean acidification. This study
      investigates community composition and activity responses to experimental ocean
      acidification in biofilms from the Australian Great Barrier Reef. Natural
      biofilms grown on glass slides were exposed for 11 d to four controlled pCO(2)
      concentrations representing the following scenarios: A) pre-industrial (~300
      ppm), B) present-day (~400 ppm), C) mid century (~560 ppm) and D) late century
      (~1140 ppm). Terminal restriction fragment length polymorphism and clone library
      analyses of 16S rRNA genes revealed CO(2) -correlated bacterial community shifts
      between treatments A, B and D. Observed bacterial community shifts were driven by
      decreases in the relative abundance of Alphaproteobacteria and increases of
      Flavobacteriales (Bacteroidetes) at increased CO(2) concentrations, indicating pH
      sensitivity of specific bacterial groups. Elevated pCO(2) (C + D) shifted biofilm
      algal communities and significantly increased C and N contents, yet O(2) fluxes,
      measured using in light and dark incubations, remained unchanged. Our findings
      suggest that bacterial biofilm communities rapidly adapt and reorganize in
      response to high pCO(2) to maintain activity such as oxygen production.

PMID- 21906227
TI  - A period of transition.

PMID- 21906226
TI  - Interleukin-15 treatment improves glucose homeostasis and insulin sensitivity in
      obese mice.
AB  - The prevalence of metabolic diseases associated with obesity, such as type 2
      diabetes, continues to rise along with obesity rates. Recently, obesity has been
      described as an inflammatory condition, suggesting a link between the
      dysregulation in proinflammatory cytokine production and the aetiology of these
      metabolic diseases. While known as an immunomodulatory cytokine, Interleukin-15
      (IL-15) has been shown to have effects on adipose tissue and induce weight loss
      in diet-induced obese mice. As weight loss improves glucose homeostasis, the goal
      of this study was to determine whether IL-15 impacts glucose regulation in a
      mouse model of diet-induced obesity. Our data demonstrate that IL-15 treatment
      significantly improves insulin sensitivity and glucose and insulin responses to
      an oral glucose challenge compared to obese counterparts and/or lean controls.
      These results show that IL-15 may be a novel therapeutic target for the treatment
      of obesity and its associated abnormal glucose regulation.

PMID- 21906228
TI  - Dialectic of the university: a critique of instrumental reason in graduate
      nursing education.
AB  - Our analysis in this paper unfolds on two levels: a critique of the 'realities'
      of graduate nursing education and an argument to sustain its 'ideals'. We open
      for discussion an aspect of graduate nursing education dominated by instrumental
      reason, namely the research industry, using an internal critique approach
      developed by Max Horkheimer and Theodor Adorno of the Early Frankfurt School. As
      we explain, internal critique arises out of, and relies on, the mismatch between
      goals, or 'ideals', and existing realities. Thinking about 'ideals' of the
      academy, we draw on Hans-Georg Gadamer's view of the university as a place to
      think freely, creatively, and critically. The contemporary realities of the
      university, on the other hand, that emphasize the market values of the research
      industry forcefully shape nursing academic scholarship in a particular direction.
      In our attempt to recognize and disrupt the forces of the research industry with
      its instrumental reason, we consider Judith Butler's writings on how norms
      operate in society. We show that our growing involvement in the research industry
      makes it very difficult to disentangle ourselves from that situation. The values
      of the research industry actually suppress the very ideals of education and
      scholarship that we would like to uphold. As a contra-force, the internal
      critique of the 'existing realities' in the graduate nursing education unmasks
      the tyranny of the research industry and makes visible the importance of
      sustaining the higher goals and ideals in nursing scholarship.

PMID- 21906220
TI  - Photoautotrophic symbiont and geography are major factors affecting highly
      structured and diverse bacterial communities in the lichen microbiome.
AB  - Although common knowledge dictates that the lichen thallus is formed solely by a
      fungus (mycobiont) that develops a symbiotic relationship with an alga and/or
      cyanobacterium (photobiont), the non-photoautotrophic bacteria found in lichen
      microbiomes are increasingly regarded as integral components of lichen thalli.
      For this study, comparative analyses were conducted on lichen-associated
      bacterial communities to test for effects of photobiont-types (i.e. green algal
      vs. cyanobacterial), mycobiont-types and large-scale spatial distances (from
      tropical to arctic latitudes). Amplicons of the 16S (SSU) rRNA gene were examined
      using both Sanger sequencing of cloned fragments and barcoded pyrosequencing.
      Rhizobiales is typically the most abundant and taxonomically diverse order in
      lichen microbiomes; however, overall bacterial diversity in lichens is shown to
      be much higher than previously reported. Members of Acidobacteriaceae,
      Acetobacteraceae, Brucellaceae and sequence group LAR1 are the most commonly
      found groups across the phylogenetically and geographically broad array of
      lichens examined here. Major bacterial community trends are significantly
      correlated with differences in large-scale geography, photobiont-type and
      mycobiont-type. The lichen as a microcosm represents a structured, unique
      microbial habitat with greater ecological complexity and bacterial diversity than
      previously appreciated and can serve as a model system for studying larger
      ecological and evolutionary principles.

PMID- 21906229
TI  - Evil and elder abuse: intersections of Paul Ricoeur's and Simone Weil's
      perspectives on evil with one abused older woman's narrative.
AB  - Doing violence and evil always indirectly or directly leads to making someone
      else suffer. Such is the dialogical structure of evil and it seems to be the
      dialogical structure of elder abuse as well. There is a perturbing sameness
      between definitions of evil and definitions of elder abuse. It is hard at times
      to see how or if there is any line of demarcation between the subjects. Two
      modern-day philosophers, Paul Ricoeur and Simone Weil have delved particularly
      into the concept of evil. The symbolism Ricoeur analyses in depth is that of
      defilement, sin, and guilt and the concept of the servile will. Integral in
      Weil's description of evil are the concepts of suffering and the special
      situation of extreme suffering, termed affliction. Grounded in the writings of
      Ricoeur and Weil, this paper is a series of reflections on the intersection of
      evil and elder abuse as exemplified in the narrative of an abused older woman.
      This woman provided around the clock care at home for her husband who had
      vascular dementia. She was also abused by her husband. This was witnessed by both
      family and others but no one intervened. In her narrative there were indications
      of defilement, sin, guilt, and true affliction as a servile will. This paper
      illuminates the evil of elder abuse that is harm and suffering, and the challenge
      of untangling issues of blame, free will, responsibility, and self-determinism.
      When engaging with abused, older persons it can be worthwhile for nurses to enter
      the encounter with non-judgemental compassion founded on the human to human
      connection and recognition of our mutual fallibility and potential for evil that
      is part of our human fragility.

PMID- 21906230
TI  - Understanding the relational aspects of learning with, from, and about the other.
AB  - Frequently heard among healthcare providers, administrators, students, and
      educators, especially within the context of interprofessional collaboration, is
      the phrase: learning with, from, and about the other. Our purpose in writing this
      article was to explore the relational aspects of interprofessional collaboration
      and provide a conversational perspective on how this phrase may be co-constructed
      by members of the interprofessional team, to achieve a contextual understanding
      for enhanced practice. It is through understanding and analysing the meaning of
      commonly held words and phrases that we can begin to understand the differences
      between transactional ways of gaining knowledge and begin to understand how a
      transformational shift in attitude, identity, and practice can promote learning
      with, from, and about the other.

PMID- 21906231
TI  - Socio-phenomenology and conversation analysis: interpreting video lifeworld
      healthcare interactions.
AB  - This article uses a socio-phenomenological methodology to develop knowledge and
      understanding of the healthcare consultation based on the concept of the
      lifeworld. It concentrates its attention on social action rather than strategic
      action and a systems approach. This article argues that patient-centred care is
      more effective when it is informed through a lifeworld conception of human mutual
      shared interaction. Videos offer an opportunity for a wide audience to experience
      the many kinds of conversations and dynamics that take place in consultations.
      Visual sociology used in this article provides a method to organize video
      emotional, knowledge and action conversations as well as dynamic typical
      consultation situations. These interactions are experienced through the video
      materials themselves unlike conversation analysis where video materials are first
      transcribed and then analysed. Both approaches have the potential to support
      intersubjective learning but this article argues that a video lifeworld schema is
      more accessible to health professionals and the general public. The typical
      interaction situations are constructed through the analysis of video materials of
      consultations in a London walk-in centre. Further studies are planned in the
      future to extend and replicate results in other healthcare services. This method
      of analysis focuses on the ways in which the everyday lifeworld informs face-to
      face person-centred health care and supports social action as a significant
      factor underpinning strategic action and a systems approach to consultation
      practice.

PMID- 21906232
TI  - The 'demented other' or simply 'a person'? Extending the philosophical discourse
      of Naue and Kroll through the situated self.
AB  - This article presents a critique of an article previously featured in Nursing
      Philosophy (10: 26-33) by Ursula Naue and Thilo Kroll, who suggested that people
      living with dementia are assigned a negative status upon receipt of a diagnosis,
      holding the identity of the 'demented other'. Specifically, in this critique, we
      suggest that unwitting use of the adjective 'demented' to define a person living
      with the condition is ill-informed and runs a risk of defining people through
      negative (self-)attributes, which has a deleterious impact upon that person's
      social and relational personae. Moreover, use of the locution 'demented'
      reinforces a divide between the 'demented' (them) and the 'healthy others' (us).
      Social constructionist theory, malignant positioning and viewing people with
      dementia as semiotic subjects are the philosophical pillars through which we
      construct the main arguments of the critique. The article concludes with the
      voice of one of the authors, a younger person with dementia, asking for language
      in dementia care to be carefully reconsidered and reframed and for the
      recognition of the diagnosed person's agency in the conduct of their day-to-day
      lives.

PMID- 21906237
TI  - Deaths in early pregnancy. The eight report of the confidential enquiries into
      maternal deaths in the United Kingdom.

PMID- 21906238
TI  - Saving mothers' lives. Reviewing maternal deaths to make motherhood safer: 2006
      2008.

PMID- 21906239
TI  - The term 'Pregnancy of unknown location' is staying put.

PMID- 21906244
TI  - Multivariate risk scores and patient outcomes in advanced heart failure.
AB  - Significant improvements in survival have occurred for patients with advanced
      heart failure, with an increasing array of therapeutic options sharing quite
      varied properties of cost, invasiveness, and impact on life expectancy. Risk
      models allow patients and providers to achieve a better understanding of
      prognosis than is possible through unstructured holistic assessment. This article
      reviews scoring systems for heart failure prognostication in the general sense
      and in the setting of providing answers to specific clinical queries. Topics
      addressed include outpatient survival, risk of inpatient and post-discharge
      mortality, potential changes to clinician decision-making through better
      understanding of prognosis, and mortality after having a left ventricular assist
      device placed or receiving an implantable cardiac-defibrillator.

PMID- 21906245
TI  - Pharmacologic therapy for New York Heart Association class IV heart failure.
AB  - As the incidence of heart failure increases, the number of patients with advanced
      heart failure is anticipated to grow. Substantial progress in the treatment of
      heart failure has been achieved over the past few decades. Several classes of
      medications have been studied and found effective, including beta-blockers,
      angiotensin converting enzyme inhibitors or angiotensin receptor blockers,
      aldosterone antagonists, vasodilators, digoxin, and inotropes. The evidence base
      for the use of these medications in the treatment of patients with New York Heart
      Association (NYHA) class IV heart failure is reviewed.

PMID- 21906246
TI  - Device therapy in advanced heart failure: what to put in and what to turn off:
      remote telemonitoring and implantable hemodynamic devices for advanced heart
      failure monitoring in the ambulatory setting and the evolving role of cardiac
      resynchronization therapy.
AB  - Despite evidence based medical and pharmacologic advances the management of heart
      failure remains challenging, especially in the ambulatory setting. There is an
      urgent need to develop strategies to reduce hospitalizations and re-admission
      rates for heart failure in general. This focused review illustrates the potential
      role for remote telemonitoring and implantable hemodynamic devices to address
      this significant issue. We also explore the growth of cardiac resynchronization
      therapy and how it has evolved into another tool in our armamentarium for
      hemodynamic monitoring.

PMID- 21906247
TI  - Patient selection for left ventricular assist devices.
AB  - Mechanical circulatory support has become an increasingly common method of
      supporting patients with advanced heart failure. Paramount to the recent progress
      observed with this therapy has been a greater understanding of patient selection
      criteria as a primary determinant of early and late patient outcomes. Prior to
      device implant, patients should undergo a multidisciplinary evaluation of
      cardiovascular, noncardiovascular, and psychosocial factors that influence
      postoperative outcomes. The use of multivariable risk scores may also be useful
      to guide discussions with patients and families regarding the relative risks of
      different therapeutic alternatives. Despite an evidence base that provides
      guiding principles in patient selection for mechanically assisted circulation,
      several aspects of the evaluation require further refinement, including
      development of tools to objectively assess psychosocial parameters, and
      definition and validation of measures of right ventricular dysfunction that
      preclude successful isolated left ventricular support.

PMID- 21906248
TI  - Ethics in the treatment of advanced heart failure: palliative care and end-of
      life issues.
AB  - Advanced heart failure (HF) is a life-shortening condition, yet there are
      increasing treatments and implantable devices available to clinicians to manage
      patients with advanced HF. Planning for adverse events and the end of life,
      formulated as "preparedness planning," can be integrated into HF care early in
      illness. Discussions that acknowledge the uncertainty of HF course and length of
      life and incorporate patient and family goals and values facilitates this
      planning. Clear processes for weighing potential benefits and burdens of
      interventions and therapies should accompany decision-making. Device implantation
      decision-making can acknowledge alternative avenues of care to the device and
      identify situations in which the device might be deactivated in the future.
      Symptom assessment and management potentially improve quality of life in patients
      with advanced HF. Management of symptoms should integrate HF therapies as well as
      other treatments. Collaboration between HF providers, palliative care clinicians,
      and, if appropriate, hospice clinicians will improve care for HF patients and
      their families.

PMID- 21906249
TI  - Contemporary management and research directions in advanced heart failure: where
      are we going?
AB  - Advanced heart failure (AHF) is not a uniform disorder, but is rather a
      heterogeneous group of patients with varying clinical presentations and
      definitions. It is growing in magnitude and represents a major public health
      problem. Herein we describe contemporary care of the patient with AHF, novel
      medical therapies, and mechanical circulatory assist devices. We speculate where
      progress has been made and where the major gaps in knowledge remain. Clearly,
      there is ample opportunity for research and discovery to further advance the care
      of these very sick patients.

PMID- 21906250
TI  - Continuous hemodynamic monitoring in patients with mild to moderate heart
      failure: results of The Reducing Decompensation Events Utilizing Intracardiac
      Pressures in Patients With Chronic Heart Failure (REDUCEhf) trial.
AB  - Clinical trial results support the hypothesis that implantable hemodynamic
      monitoring (IHM) systems may reduce hospitalizations among patients with chronic
      heart failure (HF). The Reducing Decompensation Events Utilizing Intracardiac
      Pressures in Patients With Chronic Heart Failure (REDUCE hf  ) study was a
      prospective, randomized, multicenter, single-blinded trial that enrolled patients
      with New York Heart Association class II or III symptoms, an indication for an
      implantable cardioverter-defibrillator (ICD), and a previous HF hospitalization.
      A combination IHM-ICD was implanted and patients were randomly assigned to a
      treatment group in which hemodynamic information was used or a control group in
      which hemodynamic information was not available. Patients were followed for 12
      months to evaluate the primary efficacy end point of HF hospitalizations,
      emergency department visits, or urgent clinic visits. The trial was designed to
      enroll 1300 patients, but stopped at 400 patients because of IHM lead failures
      experienced from previous trials. A total of 202 treatment patients and 198
      controls were randomized for 12-month follow-up. The primary safety end point was
      met, but the rate of HF equivalents was not different between groups. REDUCE hf
      was unable to test clinical efficacy end points adequately. The device combining
      IHM-ICD technology was safe and functioned appropriately. Patients at high risk
      for decompensated HF have high baseline filling pressures and demonstrate
      consistent increases as the process of congestion worsens to the time of
      hospitalization.

PMID- 21906252
TI  - Late cytomegalovirus transmission and impact of T-depletion in clinical islet
      transplantation.
AB  - The epidemiology of cytomegalovirus infection (CMV) in islet transplantation (IT)
      is not well defined. This study defines incidence, transmission and clinical
      sequelae of CMV reactivation or disease in 121 patients receiving 266 islet
      infusions at a single institution. The donor (D)/recipient (R) serostatus was
      D+/R- 31.2%, D+/R+ 26.3%, D-/R+ 13.2% and D-/R- 29.3%. CMV prophylaxis with oral
      ganciclovir/valganciclovir was given in 68%. CMV infection occurred in 14/121
      patients (11.6%); six had asymptomatic seroconversion and eight others had
      positive viremia (six asymptomatic and two with CMV febrile symptoms). Median
      peak viral loads were 1755 copies/mL (range 625-9 100 000). Risk factors for
      viremia included lymphocyte depletion (thymoglobulin or alemtuzumab, p < 0.001).
      Viremia was more common in D+/R+ versus D+/R- (p = 0.12), occurring mostly late
      after transplant (median 306 days). Presumed transmission from IT occurred in
      8/83 of D+/R- procedures (9.6%). Of the two cases of CMV disease, one resulted
      from islet transmission from a CMV positive donor (D+/R-); the other was due to
      de novo exogenous infection (D-/R-). Therefore, CMV transmission presents rarely
      after IT and with low incidence compared to solid organ transplantation, but
      occurs late posttransplant. The use of lymphocyte depleting therapies is a
      primary risk factor.

PMID- 21906253
TI  - Rational rationing or discrimination: balancing equity and efficiency
      considerations in kidney allocation.
AB  - After 6 years of deliberation, the Organ Procurement and Transplantation Network
      recently released a concept document proposing changes to the kidney allocation
      algorithm, sparking a heated debate about priority-setting of scarce health
      resources and discrimination. Proponents of the proposal argue that it will
      result in an additional 15,223 life years following transplant annually for
      recipients, yet the benefit will not be equally distributed and will likely
      benefit younger patients. Critics argue that the new model will promote age
      discrimination and may lead to a further decrease in live kidney donation. If
      true, these concerns could undermine fairness and damage public trust in the
      organ allocation system. We address these objections and consider their merit,
      highlighting both benefits and shortcomings of the proposal. We argue that,
      despite weaknesses of the proposal and the importance of maintaining consistency
      in patient and provider expectations over time, the proposal represents a needed
      first step in balancing equity and efficiency.

PMID- 21906254
TI  - The emerging role of the TIM molecules in transplantation.
AB  - Since their discovery in 2001, the T-cell immunoglobulin mucin (TIM) family
      members have been shown to play important roles in the regulation of immune
      responses. The TIM family comprises of eight genes in the mouse, three of which
      are conserved in humans (TIM-1, TIM-3 and TIM-4). Initially, TIM-1 and TIM-3 were
      thought to be expressed solely on T cells. However, emerging data suggest a much
      broader expression pattern where their presence on APCs confers differing
      functions, including the ability to mediate phagocytosis. In contrast, TIM-4 is
      exclusively expressed on APCs. Together, the TIM molecules provide a functional
      repertoire for determining the fate of T-cell activation and differentiation. To
      date, much of the knowledge about the TIM family members has been garnered from
      the models of asthma, allergy and autoimmunity. More recently, data from
      experimental models of transplantation demonstrate that TIM family members also
      have a key role in alloimmunity. This review will serve to highlight the emerging
      data regarding this unique family of molecules and to identify their potential in
      transplantation tolerance.

PMID- 21906255
TI  - Posttransplant donor-specific anti-HLA antibodies negatively impact pancreas
      transplantation outcome.
AB  - During a 9-year follow-up, 167 consecutive pancreas transplant recipients (152
      simultaneous pancreas-kidney [SPK]) were followed for the detection of
      posttransplant anti-HLA antibodies. Forty patients (24%) developed anti-HLA
      antibodies, 26 (65%) had donor-specific antibodies (DSA; 61% anticlass 2) and 14
      (35%) non-DSA (78.6% anticlass 1). More rejection episodes were observed in
      patients with positive anti-HLA antibodies than in patients without antibodies
      (42.5% vs. 11%; p = 0.001), with the highest incidence observed in DSA patients
      (53.8%). More severe rejections (according to rescue therapy) were observed in
      DSA patients compared to non-DSA (p < 0.05) or to negative patients (p < 0.001).
      Contrasting with the kidney, pancreas graft survival did not differ between
      patients with or without anti-HLA antibodies. On the contrary, pancreas and
      kidney survivals were significantly lower in DSA positive patients (75% for both
      organs) as compared to non-DSA positive patients (100% for pancreas and 92% for
      kidney) or to HLA-negative patients (91% for pancreas and 89% for kidney).
      Nontechnical pancreas and kidney graft failures were significantly higher in
      positive than in negative anti-HLA patients (32.5% vs. 11%; p < 0.01). Occurrence
      of posttransplant DSA was an independent risk factor for both pancreas and kidney
      survival (HR 3.2; p = 0.039) in diabetic transplant recipients.

PMID- 21906256
TI  - Hypothermic reconditioning by gaseous oxygen improves survival after liver
      transplantation in the pig.
AB  - The quality of cold-stored livers declines with the extension of ischemic time
      and the risk of primary dys- or nonfunction increases. Here, we provide in vivo
      evidence for the efficacy of the previously developed end-ischemic gaseous oxygen
      persufflation technique to resuscitate liver grafts after extended storage times.
      Porcine livers were recovered according to standard multiorgan procurement
      protocol. Control livers were cold stored in histidine tryptophan ketoglutarate
      solution for 10 h (cold storage [CS]; n = 6) at 4 degrees C. In the treatment
      group (n = 6), livers were additionally subjected to hypothermic reconditioning
      (HR) by gaseous oxygen persufflation via the caval vein for 2 h before
      transplantation. Viability was assessed by orthotopic liver transplantation and 1
      week follow-up. HR significantly improved pretransplant energy charge and initial
      graft function after transplantation. One week survival after CS was 0% whereas
      five of six pigs (83%) survived in the HR group. At that time, coagulation
      parameters were in the normal range and histological analysis disclosed healthy
      liver tissue with normal trabecular architecture in the treated grafts. Molecular
      analyses identify the prevention of ischemia-induced decline of cellular
      autophagy and mitigation of innate immune machinery (high-mobility group protein
      B1, interferon-beta) as operative mechanisms among the protective effects
      provided by HR.

PMID- 21906257
TI  - Impact of cold ischemia time on graft survival among ECD transplant recipients: a
      paired kidney analysis.
AB  - Delays in expanded criteria donor (ECD) kidney placement increases cold ischemia
      times (CIT) potentially leading to discard. The effect of increased CIT on ECD
      kidney transplant outcomes is unknown. We evaluated paired ECD kidneys (derived
      from the same donor transplanted to different recipients) from the SRTR registry
      transplanted between 1995 and 2009 (n = 17,514). To test the effect of CIT, we
      excluded paired transplants with the same CIT (n = 3286). Of 14,230 recipients
      (7115 donors) the median difference in CIT was 5 h (Q1 = 3 h, Q3 = 9 h). Delayed
      graft function (DGF) was significantly more likely between pairs with greater CIT
      (35% vs. 31%, p < 0.001) including substantially higher rates for CIT differences
      >= 15 h (42%). Overall graft loss was not significantly different between
      recipients with higher CIT relative to paired donor recipients with lower CIT (p
      = 0.47) or for pairs with differences of 1-3 h (p = 0.90), 4-9 h (p = 0.41), 10
      14 h (p = 0.36) or >= 15 h (p = 0.10). Results were consistent in multivariable
      models adjusted for recipient factors. Although increasing cold ischemia time is
      a risk factor for DGF among ECD kidney transplants, there is no effect on graft
      survival which may suggest an important utility for donor kidneys that may not
      currently be considered viable.

PMID- 21906258
TI  - Impact of adjuvanted H1N1 vaccine on cell-mediated rejection in heart transplant
      recipients.
AB  - During the H1N1 influenza virus pandemic, vaccination of high risk groups
      including solid-organ transplant recipients was advised. A retrospective case
      control study of 60 heart transplant patients, 15 having received the H1N1 virus
      antigen and ASO3 adjuvant vaccine (GlaxoSmithKline, Mississauga, ON, Canada)
      within 21 days and 45 having not been vaccinated, all undergoing routine
      surveillance endmyocardial biopsies, was performed. The overall rate of cellular
      rejection (all grades) was not statistically different between groups; however,
      acute cellular rejection, >=grade 2 (1990 ISHLT criteria), was more frequent
      among those having recently vaccinated (control: 1/45 vs. 6/15, p = 0.001). On
      multivariate analysis, the only risk factor found to be associated with acute
      cellular rejection was recent H1N1 viral antigen and adjuvant vaccination (OR
      26.5: 95% CI 02.59-270.5). Vaccine adjuvants increase host response to vaccine
      antigens by immune upregulation potentially increasing risk of rejection in solid
      organ transplant recipients. The potential hazard of vaccination this study
      raises must be weighed with the clear benefit vaccination has proven to be.

PMID- 21906260
TI  - Donor-specific alloantibody upregulation after influenza vaccination in
      transplant recipients.

PMID- 21906259
TI  - Impact of donor left ventricular hypertrophy on survival after heart transplant.
AB  - Left ventricular hypertrophy (LVH) of the donor heart is believed to increase the
      risk of allograft failure after transplant. However this effect is not well
      quantified, with variable findings from single-center studies. The United Network
      for Organ Sharing database was used to analyze the effect of donor LVH on
      recipient survival. Three cohorts, selected in accordance with the American
      Society of Echocardiography guidelines, were examined: recipients of allografts
      without LVH (<1.1 cm), with mild LVH (1.1-1.3 cm) and with moderate-severe LVH
      (>= 1.4 cm). The study group included 2626 patients with follow-up of up to 3.3
      years. Mild LVH was present in 38% and moderate-severe LVH in 5.6% of allografts.
      Predictors of mortality included a number of donor and recipient characteristics,
      but not LVH. However, a subgroup analysis showed an increased risk of death in
      recipients of allografts with LVH and donor age >55 years, and in recipients of
      allografts with LVH and ischemic time >= 4 h. In the contemporary era, close to
      half of all transplanted allografts demonstrate LVH, and survival of these
      recipients is similar to those without LVH. However, the use of allografts with
      LVH in association with other high-risk characteristics may result in increased
      mortality.

PMID- 21906262
TI  - Cognitive impairments in adult mice with constitutive inactivation of RIP140 gene
      expression.
AB  - Receptor-interacting protein 140 (RIP140) is a negative transcriptional
      coregulator of nuclear receptors such as estrogen, retinoic acid or
      glucocorticoid receptors. Recruitment of RIP140 results in an inhibition of
      target gene expression through different repressive domains interacting with
      histone deacetylases or C-terminal binding proteins. In this study, we analyzed
      the role of RIP140 activity in memory processes using RIP140-deficient transgenic
      mice. Although the RIP140 protein was clearly expressed in the brain (cortical
      and hippocampus areas), the morphological examination of RIP140(-/-)  mouse brain
      failed to show grossly observable alterations. Using male 2-month-old RIP140(-/-)
      , RIP140(+/-)  or RIP140(+/+)  mice, we did not observe any significant
      differences in the open-field test, rotarod test and in terms of spontaneous
      alternation in the Y-maze. By contrast, RIP140(-/-)  mice showed long-term memory
      deficits, with an absence of decrease in escape latencies when animals were
      tested using a fixed platform position procedure in the water maze and in the
      passive avoidance test. Noteworthy, RIP140(-/-)  mice showed decreased swimming
      speed, suggesting swimming alterations that may in part account for the marked
      alterations measured in the water maze. Moreover, RIP140(+/-)  and RIP140(-/-) 
      mice showed a significant increase in immobility time in the forced swimming test
      as compared with wild-type animals. These observations showed that RIP140 gene
      depletion results in learning and memory deficits as well as stress response,
      bringing to light a major role for this transcriptional coregulator in the
      neurophysiological developmental mechanisms underlying cognitive functions.

PMID- 21906264
TI  - Relevant uses of surface proteins--display on self-organized biological
      structures.
AB  - Proteins are often found attached to surfaces of self-assembling biological units
      such as whole microbial cells or subcellular structures, e.g. intracellular
      inclusions. In the last two decades surface proteins were identified that could
      serve as anchors for the display of foreign protein functions. Extensive protein
      engineering based on structure-function data enabled efficient display of
      technically and/or medically relevant protein functions. Small size, diversity of
      the anchor protein as well as support structure, genetic manipulability and
      controlled cultivation of phages, bacterial cells and yeasts contributed to the
      establishment of designed and specifically functionalized tools for applications
      as sensors, catalysis, biomedicine, vaccine development and library-based
      screening technologies. Traditionally, phage display is employed for library
      screening but applications in biomedicine and vaccine development are also
      perceived. For some diagnostic purposes phages are even too small in size so
      other carrier materials where needed and gave way for cell and yeast display.
      Only recently, intracellular inclusions such as magnetosomes,
      polyhydroxyalkanoate granules and lipid bodies were conceived as stable
      subcellular structures enabling the display of foreign protein functions and
      showing potential as specific and tailor-made devices for medical and
      biotechnological applications.

PMID- 21906265
TI  - Biofilm formation in Streptococcus pneumoniae.
AB  - Biofilm-grown bacteria are refractory to antimicrobial agents and show an
      increased capacity to evade the host immune system. In recent years, studies have
      begun on biofilm formation by Streptococcus pneumoniae, an important human
      pathogen, using a variety of in vitro model systems. The bacterial cells in these
      biofilms are held together by an extracellular matrix composed of DNA, proteins
      and, possibly, polysaccharide(s). Although neither the precise nature of these
      proteins nor the composition of the putative polysaccharide(s) is clear, it is
      known that choline-binding proteins are required for successful biofilm
      formation. Further, many genes appear to be involved, although the role of each
      appears to vary when biofilms are produced in batch or continuous culture.
      Prophylactic and therapeutic measures need to be developed to fight S. pneumoniae
      biofilm formation. However, much care needs to be taken when choosing strains for
      such studies because different S. pneumoniae isolates can show remarkable genomic
      differences. Multispecies and in vivo biofilm models must also be developed to
      provide a more complete understanding of biofilm formation and maintenance.

PMID- 21906267
TI  - Clinical applicability of functional hemodynamic monitoring.
AB  - Recent interest in functional hemodynamic monitoring for the bedside assessment
      of cardiovascular insufficiency has heightened. Functional hemodynamic monitoring
      is the assessment of the dynamic interactions of hemodynamic variables in
      response to a defined perturbation. Accordingly, fluid responsiveness can be
      predicted in a quantities fashion by measuring as arterial pulse pressure
      variation and left ventricular stroke volume variation during positive pressure
      breathing or the change in cardiac output response to a passive leg raising
      maneuver. However, volume responsiveness, though important, reflects only part of
      the overall spectrum of functional physiological variables that can be measured
      to define physiologic state and monitor response to therapy. Dynamic tissue O2
      saturation (StO2) responses to complete stop flow conditions, which can be
      created by measuring hand StO2 and occluding flow with a blood pressure cuff,
      assesses cardiovascular sufficiency and microcirculatory blood flow distribution.
      Furthermore, these measures can be made increasingly more sensitive and specific
      if coupled to other "traditional" measures of organ perfusion, such as blood
      lactate levels.

PMID- 21906268
TI  - Training in critical care echocardiography.
AB  - Echocardiography is useful for the diagnosis and management of hemodynamic
      failure in the intensive care unit so that competence in some elements of
      echocardiography is a core skill of the critical care specialist. An important
      issue is how to provide training to intensivists so that they are competent in
      the field. This article will review issues related to training in critical care
      echocardiography.

PMID- 21906266
TI  - New materials and devices for preventing catheter-related infections.
AB  - Catheters are the leading source of bloodstream infections for patients in the
      intensive care unit (ICU). Comprehensive unit-based programs have proven to be
      effective in decreasing catheter-related bloodstream infections (CR-BSIs). ICU
      rates of CR-BSI higher than 2 per 1,000 catheter-days are no longer acceptable.
      The locally adapted list of preventive measures should include skin antisepsis
      with an alcoholic preparation, maximal barrier precautions, a strict catheter
      maintenance policy, and removal of unnecessary catheters. The development of new
      technologies capable of further decreasing the now low CR-BSI rate is a major
      challenge. Recently, new materials that decrease the risk of skin-to-vein
      bacterial migration, such as new antiseptic dressings, were extensively tested.
      Antimicrobial-coated catheters can prevent CR-BSI but have a theoretical risk of
      selecting resistant bacteria. An antimicrobial or antiseptic lock may prevent
      bacterial migration from the hub to the bloodstream. This review discusses the
      available knowledge about these new technologies.

PMID- 21906269
TI  - A simple method to evaluate the number of bradyrhizobia on soybean seeds and its
      implication on inoculant quality control.

PMID- 21906270
TI  - Reduction of exogenous ketones depends upon NADPH generated photosynthetically in
      cells of the cyanobacterium Synechococcus PCC 7942.
AB  - Effective utilization of photosynthetic microorganisms as potential biocatalysts
      is favorable for the production of useful biomaterials and the reduction of
      atmospheric CO2. For example, biocatalytic transformations are used in the
      synthesis of optically active alcohols. We previously found that ketone reduction
      in cells of the cyanobacterium Synechococcus PCC 7942 is highly enantioselective
      and remarkably enhanced under light illumination. In this study, the mechanism of
      light-enhanced ketone reduction was investigated in detail using several
      inhibitors of photosynthetic electron transport and of enzymes of the Calvin
      cycle. It is demonstrated that light intensity and photosynthesis inhibitors
      significantly affect the ketone reduction activity in Synechococcus. This
      indicates that the reduction correlates well with photosynthetic activity.
      Moreover, ketone reduction in Synechococcus specifically depends upon NADPH and
      not NADH. These results also suggest that cyanobacteria have the potential to be
      utilized as biocatalytic systems for direct usage of light energy in various
      applications such as syntheses of useful compounds and remediation of
      environmental pollutants.

PMID- 21906271
TI  - Diagnosis of invasive candidiasis in the ICU.
AB  - Invasive candidiasis ranges from 5 to 10 cases per 1,000 ICU admissions and
      represents 5% to 10% of all ICU-acquired infections, with an overall mortality
      comparable to that of severe sepsis/septic shock. A large majority of them are
      due to Candida albicans, but the proportion of strains with decreased sensitivity
      or resistance to fluconazole is increasingly reported. A high proportion of ICU
      patients become colonized, but only 5% to 30% of them develop an invasive
      infection. Progressive colonization and major abdominal surgery are common risk
      factors, but invasive candidiasis is difficult to predict and early diagnosis
      remains a major challenge. Indeed, blood cultures are positive in a minority of
      cases and often late in the course of infection. New nonculture-based laboratory
      techniques may contribute to early diagnosis and management of invasive
      candidiasis. Both serologic (mannan, antimannan, and betaglucan) and molecular
      (Candida-specific PCR in blood and serum) have been applied as serial screening
      procedures in high-risk patients. However, although reasonably sensitive and
      specific, these techniques are largely investigational and their clinical
      usefulness remains to be established. Identification of patients susceptible to
      benefit from empirical antifungal treatment remains challenging, but it is
      mandatory to avoid antifungal overuse in critically ill patients. Growing
      evidence suggests that monitoring the dynamic of Candida colonization in surgical
      patients and prediction rules based on combined risk factors may be used to
      identify ICU patients at high risk of invasive candidiasis susceptible to benefit
      from prophylaxis or preemptive antifungal treatment.

PMID- 21906272
TI  - Cancer vaccines at an inflexion point: what next?
AB  - With the approval of the first therapeutic cancer vaccines for veterinarian and
      human use, the field reached a significant milestone after a considerable
      interval of tumultuous research and development marked by numerous ups and downs.
      As the mechanism of action and clinical benefit afforded by this class of agents
      are starkly different from that of conventional or small targeted therapies for
      cancer, there are still numerous hurdles that need to be overcome to fully
      unleash their potential. These challenges and efforts are illustrated in a book
      just published on this subject, a non-exhaustive yet representative synopsis of
      the latest advances in cancer vaccine technologies in various stages of
      development. Major lessons resulting from clinical testing of cancer vaccines and
      other immune interventions, are being integrated in novel, cutting edge platform
      technologies that blur the distinction between passive and active immunotherapies
      as well as carry the promise of fundamentally changing and improving the
      management of patients with cancer.

PMID- 21906274
TI  - Vascular endothelial growth factor-A and chemokine ligand (CCL2) genes are
      upregulated in peripheral blood mononuclear cells in Indian amyotrophic lateral
      sclerosis patients.
AB  - BACKGROUND: We have earlier shown that protein levels of vascular endothelial
      growth factor-A (VEGF-A) and chemokine ligand-2 (CCL2) were elevated in Indian
      amyotrophic lateral sclerosis (ALS) patients. Here, we report the mRNA levels of
      VEGF-A and CCL2 in Indian ALS patients since they display extended survival after
      disease onset. METHODS: VEGF-A and CCL2 mRNA levels were measured in peripheral
      blood mononuclear cells (PBMCs) of 50 sporadic Indian ALS patients using Real
      Time Polymerase Chain Reaction (PCR) and compared with normal controls (n = 50).
      Their levels were adjusted for possible confounders like cigarette smoking,
      alcohol and meat consumption. RESULTS: VEGF-A and CCL2 mRNA levels were found to
      be significantly elevated in PBMCs in ALS patients as compared to controls. PBMCs
      from definite ALS revealed higher VEGF-A mRNA expression as compared to probable
      and possible ALS. CCL2 mRNA levels were found to be unaltered when definite,
      probable and possible ALS were compared. PBMCs from patients with respiratory
      dysfunction showed much higher VEGF-A and CCL2 elevation when compared to
      patients without respiratory dysfunction. No association of smoking, alcohol and
      meat consumption with VEGF-A and CCL2 was observed after analyzing the data with
      univariate and multivariate analysis. CONCLUSION: VEGF-A and CCL2 mRNA
      upregulation in PBMCs may have a clinico-pathological/etiological/epidemiological
      association with ALS pathogenesis. The cross-cultural and cross-ethnic
      investigations of these molecules could determine if they have any role in
      enhancing the mean survival time unique to Indian ALS patients.

PMID- 21906273
TI  - Nogo receptor is involved in the adhesion of dendritic cells to myelin.
AB  - BACKGROUND: Nogo-66 receptor NgR1 and its structural homologue NgR2 are binding
      proteins for a number of myelin-associated inhibitory factors. After neuronal
      injury, these inhibitory factors are responsible for preventing axonal outgrowth
      via their interactions with NgR1 and NgR2 expressed on neurons. In vitro, cells
      expressing NgR1/2 are inhibited from adhering to and spreading on a myelin
      substrate. Neuronal injury also results in the presence of dendritic cells (DCs)
      in the central nervous system, where they can come into contact with myelin
      debris. The exact mechanisms of interaction of immune cells with CNS myelin are,
      however, poorly understood. METHODS: Human DCs were differentiated from
      peripheral blood monocytes and mouse DCs were differentiated from wild type and
      NgR1/NgR2 double knockout bone marrow precursors. NgR1 and NgR2 expression were
      determined with quantitative real time PCR and immunoblot, and adhesion of cells
      to myelin was quantified. RESULTS: We demonstrate that human immature myeloid DCs
      express NgR1 and NgR2, which are then down-regulated upon maturation. Human
      mature DCs also adhere to a much higher extent to a myelin substrate than
      immature DCs. We observe the same effect when the cells are plated on Nogo-66-His
      (binding peptide for NgR1), but not on control proteins. Mature DCs taken from
      Ngr1/2 knockout mice adhere to a much higher extent to myelin compared to wild
      type mouse DCs. In addition, Ngr1/2 knockout had no effect on in vitro DC
      differentiation or phenotype. CONCLUSIONS: These results indicate that a lack of
      NgR1/2 expression promotes the adhesion of DCs to myelin. This interaction could
      be important in neuroinflammatory disorders such as multiple sclerosis in which
      peripheral immune cells come into contact with myelin debris.

PMID- 21906275
TI  - Activation of matrix metalloproteinases following anti-Abeta immunotherapy;
      implications for microhemorrhage occurrence.
AB  - BACKGROUND: Anti-Abeta immunotherapy is a promising approach to the prevention
      and treatment of Alzheimer's disease (AD) currently in clinical trials. There is
      extensive evidence, both in mice and humans that a significant adverse event is
      the occurrence of microhemorrhages. Also, vasogenic edema was reported in phase 2
      of a passive immunization clinical trial. In order to overcome these vascular
      adverse effects it is critical that we understand the mechanism(s) by which they
      occur. METHODS: We have examined the matrix metalloproteinase (MMP) protein
      degradation system in two previously published anti-Abeta immunotherapy studies.
      The first was a passive immunization study in which we examined 22 month old
      APPSw mice that had received anti-Abeta antibodies for 1, 2 or 3 months. The
      second is an active vaccination study in which we examined 16 month old
      APPSw/NOS2-/- mice treated with Abeta vaccination for 4 months. RESULTS: There is
      a significant activation of the MMP2 and MMP9 proteinase degradation systems by
      anti-Abeta immunotherapy, regardless of whether this is delivered through active
      vaccination or passive immunization. We have characterized this activation by
      gene expression, protein expression and zymography assessment of MMP activity.
      CONCLUSIONS: Since the MMP2 and MMP9 systems are heavily implicated in the
      pathophysiology of intracerbral hemorrhage, these data may provide a potential
      mechanism of microhemorrhage due to immunotherapy. Increased activity of the MMP
      system, therefore, is likely to be a major factor in increased microhemorrhage
      occurrence.

PMID- 21906276
TI  - Increased oxidative stress and severe arterial remodeling induced by permanent
      high-flow challenge in experimental pulmonary hypertension.
AB  - BACKGROUND: Involvement of inflammation in pulmonary hypertension (PH) has
      previously been demonstrated and recently, immune-modulating dendritic cells
      (DCs) infiltrating arterial lesions in patients suffering from idiopathic
      pulmonary arterial hypertension (IPAH) and in experimental monocrotaline-induced
      PH have been reported. Occurrence of perivascular inflammatory cells could be
      linked to local increase of oxidative stress (OS), as it has been shown for
      systemic atherosclerosis. The impact of OS on vascular remodeling in PH is still
      to be determined. We hypothesized, that augmented blood-flow could increase OS
      and might thereby contribute to DC/inflammatory cell-recruitment and smooth
      muscle-cell-proliferation. METHODS: We applied a monocrotaline-induced PH-model
      and combined it with permanent flow-challenge. Thirty Sprague-Dawley rats were
      assigned to following groups: control, monocrotaline-exposure (MCT),
      monocrotaline-exposure/pneumonectomy (MCT/PE). RESULTS: Hemodynamic exploration
      demonstrated most severe effects in MCT/PE, corresponding in histology to
      exuberant medial and adventitial remodeling of pulmonary muscular arteries, and
      intimal remodeling of smaller arterioles; lung-tissue PCR evidenced increased
      expression of DCs-specific fascin, CD68, proinflammatory cytokines (IL-6, RANTES,
      fractalkine) in MCT/PE and to a lesser extent in MCT. Major OS enzyme NOX-4 was
      maximal in MCT/PE. Antioxidative stress enzymes Mn-SOD and glutathion-peroxidase
      1 were significantly elevated, while HO-1 showed maximal expression in MCT with
      significant decrease in MCT/PE. Catalase was decreased in MCT and MCT/PE.
      Expression of NOX-4, but also of MN-SOD in MCT/PE was mainly attributed to a
      highly increased number of interstitial and perivascular CXCR4/SDF1 pathway
      recruited mast-cells. Stress markers malonedialdehyde and nitrotyrosine were
      produced in endothelial cells, medial smooth muscle and perivascular leucocytes
      of hypertensive vasculature. Immunolabeling for OX62, CD68 and actin revealed
      adventitial and medial DC- and monocyte-infiltration; in MCT/PE, medial smooth
      muscle cells were admixed with CD68+/vimentin+ cells. CONCLUSION: Our
      experimental findings support a new concept of immunologic responses to increased
      OS in MCT/PE-induced PAH, possibly linking recruitment of dendritic cells and OS
      producing mast-cells to characteristic vasculopathy.

PMID- 21906277
TI  - When is informed consent required in cluster randomized trials in health
      research?
AB  - This article is part of a series of papers examining ethical issues in cluster
      randomized trials (CRTs) in health research. In the introductory paper in this
      series, we set out six areas of inquiry that must be addressed if the cluster
      trial is to be set on a firm ethical foundation. This paper addresses the second
      of the questions posed, namely, from whom, when, and how must informed consent be
      obtained in CRTs in health research? The ethical principle of respect for persons
      implies that researchers are generally obligated to obtain the informed consent
      of research subjects. Aspects of CRT design, including cluster randomization,
      cluster level interventions, and cluster size, present challenges to obtaining
      informed consent. Here we address five questions related to consent and CRTs: How
      can a study proceed if informed consent is not possible? Is consent to
      randomization always required? What information must be disclosed to potential
      subjects if their cluster has already been randomized? Is passive consent a valid
      substitute for informed consent? Do health professionals have a moral obligation
      to participate as subjects in CRTs designed to improve professional practice?We
      set out a framework based on the moral foundations of informed consent and
      international regulatory provisions to address each of these questions. First,
      when informed consent is not possible, a study may proceed if a research ethics
      committee is satisfied that conditions for a waiver of consent are satisfied.
      Second, informed consent to randomization may not be required if it is not
      possible to approach subjects at the time of randomization. Third, when potential
      subjects are approached after cluster randomization, they must be provided with a
      detailed description of the interventions in the trial arm to which their cluster
      has been randomized; detailed information on interventions in other trial arms
      need not be provided. Fourth, while passive consent may serve a variety of
      practical ends, it is not a substitute for valid informed consent. Fifth, while
      health professionals may have a moral obligation to participate as subjects in
      research, this does not diminish the necessity of informed consent to study
      participation.

PMID- 21906278
TI  - Recruitment activities for a nationwide, population-based, group-randomized
      trial: the VA MI-Plus study.
AB  - BACKGROUND: The Veterans Health Administration (VHA) oversees the largest
      integrated healthcare system in the United States. The feasibility of a large
      scale, nationwide, group-randomized implementation trial of VHA outpatient
      practices has not been reported. We describe the recruitment and enrollment of
      such a trial testing a clinician-directed, Internet-delivered intervention for
      improving the care of postmyocardial infarction patients with multiple
      comorbidities. METHODS: With a recruitment goal of 200 eligible community-based
      outpatient clinics, parent VHA facilities (medical centers) were recruited
      because they oversee their affiliated clinics and the research conducted there.
      Eligible facilities had at least four VHA-owned and -operated primary care
      clinics, an affiliated Institutional Review Board (IRB), and no ongoing,
      potentially overlapping, quality-improvement study. Between December 2003 and
      December 2005, in two consecutive phases, we used initial and then intensified
      recruitment strategies. RESULTS: Overall, 48 of 66 (73%) eligible facilities were
      recruited. Of the 219 clinics and 957 clinicians associated with the 48
      facilities, 168 (78%) clinics and 401 (42%) clinicians participated. The median
      time from initial facility contact to clinic enrollment was 222 days, which
      decreased by over one-third from the first to the second recruitment phase
      (medians: 323 and 195 days, respectively; p < .001), when more structured
      recruitment with physician recruiters was implemented and a dedicated IRB manager
      was added to the coordinating center staff. CONCLUSIONS: Large group-randomized
      trials benefit from having dedicated physician investigators and IRB personnel
      involved in recruitment. A large-scale, nationally representative, group
      randomized trial of community-based clinics is feasible within the VHA or a
      similar national healthcare system.

PMID- 21906279
TI  - Technology assessment of automated atlas based segmentation in prostate bed
      contouring.
AB  - BACKGROUND: Prostate bed (PB) contouring is time consuming and associated with
      inter-observer variability. We evaluated an automated atlas-based segmentation
      (AABS) engine in its potential to reduce contouring time and inter-observer
      variability. METHODS: An atlas builder (AB) manually contoured the prostate bed,
      rectum, left femoral head (LFH), right femoral head (RFH), bladder, and penile
      bulb of 75 post-prostatectomy cases to create an atlas according to the recent
      RTOG guidelines. 5 other Radiation Oncologists (RO) and the AABS contoured 5 new
      cases. A STAPLE contour for each of the 5 patients was generated. All contours
      were anonymized and sent back to the 5 RO to be edited as clinically necessary.
      All contouring times were recorded. The dice similarity coefficient (DSC) was
      used to evaluate the unedited- and edited- AABS and inter-observer variability
      among the RO. Descriptive statistics, paired t-tests and a Pearson correlation
      were performed. ANOVA analysis using logit transformations of DSC values was
      calculated to assess inter-observer variability. RESULTS: The mean time for
      manual contours and AABS was 17.5- and 14.1 minutes respectively (p = 0.003). The
      DSC results (mean, SD) for the comparison of the unedited-AABS versus STAPLE
      contours for the PB (0.48, 0.17), bladder (0.67, 0.19), LFH (0.92, 0.01), RFH
      (0.92, 0.01), penile bulb (0.33, 0.25) and rectum (0.59, 0.11). The DSC results
      (mean, SD) for the comparison of the edited-AABS versus STAPLE contours for the
      PB (0.67, 0.19), bladder (0.88, 0.13), LFH (0.93, 0.01), RFH (0.92, 0.01), penile
      bulb (0.54, 0.21) and rectum (0.78, 0.12). The DSC results (mean, SD) for the
      comparison of the edited-AABS versus the expert panel for the PB (0.47, 0.16),
      bladder (0.67, 0.18), LFH (0.83, 0.18), RFH (0.83, 0.17), penile bulb (0.31,
      0.23) and rectum (0.58, 0.09). The DSC results (mean, SD) for the comparison of
      the STAPLE contours and the 5 RO are PB (0.78, 0.15), bladder (0.96, 0.02), left
      femoral head (0.87, 0.19), right femoral head (0.87, 0.19), penile bulb (0.70,
      0.17) and the rectum (0.89, 0.06). The ANOVA analysis suggests inter-observer
      variability among at least one of the 5 RO (p value = 0.002). CONCLUSION: The
      AABS tool results in a time savings, and when used to generate auto-contours for
      the femoral heads, bladder and rectum had superior to good spatial overlap.
      However, the generated auto-contours for the prostate bed and penile bulb need
      improvement.

PMID- 21906280
TI  - Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma
      cells under hypoxic conditions.
AB  - BACKGROUND: Betulinic acid (BA) is a novel antineoplastic agent under evaluation
      for tumor therapy. Because of the selective cytotoxic effects of BA in tumor
      cells (including gliomas), the combination of this agent with conservative
      therapies (such as radiotherapy and chemotherapy) may be useful. Previously, the
      combination of BA with irradiation under hypoxic conditions had never been
      studied. METHODS: In this study, the effects of 3 to 30 MUM BA on cytotoxicity,
      migration, the protein expression of PARP, survivin and HIF-1alpha, as well as
      radiosensitivity under normoxic and hypoxic conditions were analyzed in the human
      malignant glioma cell lines U251MG and U343MG. Cytotoxicity and radiosensitivity
      were analyzed with clonogenic survival assays, migration was analyzed with Boyden
      chamber assays (or scratch assays) and protein expression was examined with
      Western blot analyses. RESULTS: Under normoxic conditions, a half maximal
      inhibitory concentration (IC50) of 23 MUM was observed in U251MG cells and 24 MUM
      was observed in U343MG cells. Under hypoxic conditions, 10 MUM or 15 MUM of BA
      showed a significantly increased cytotoxicity in U251MG cells (p = 0.004 and p =
      0.01, respectively) and U343MG cells (p < 0.05 and p = 0.01, respectively). The
      combination of BA with radiotherapy resulted in an additive effect in the U343MG
      cell line under normoxic and hypoxic conditions. Weak radiation enhancement was
      observed in U251MG cell line after treatment with BA under normoxic conditions.
      Furthermore, under hypoxic conditions, the incubation with BA resulted in
      increased radiation enhancement. The enhancement factor, at an irradiation dose
      of 15 Gy after treatment with 10 or 15 MUM BA, was 2.20 (p = 0.02) and 4.50 (p =
      0.03), respectively. Incubation with BA led to decreased cell migration, cleavage
      of PARP and decreased expression levels of survivin in both cell lines.
      Additionally, BA treatment resulted in a reduction of HIF-1alpha protein under
      hypoxic conditions. CONCLUSION: Our results suggest that BA is capable of
      improving the effects of tumor therapy in human malignant glioma cells,
      particularly under hypoxic conditions. Further investigations are necessary to
      characterize its potential as a radiosensitizer.

PMID- 21906282
TI  - Cd(II) and Pb(II) complexes of the polyether ionophorous antibiotic salinomycin.
AB  - BACKGROUND: The natural polyether ionophorous antibiotics are used for the
      treatment of coccidiosis in poultry and ruminants. They are effective agents
      against infections caused by Gram-positive microorganisms. On the other hand, it
      was found that some of these compounds selectively bind lead(II) ions in in vivo
      experiments, despite so far no Pb(II)-containing compounds of defined composition
      have been isolated and characterized. To assess the potential of polyether
      ionophores as possible antidotes in the agriculture, a detailed study on their in
      vitro complexation with toxic metal ions is required. In the present paper we
      report for the first time the preparation and the structure elucidation of
      salinomycin complexes with ions of cadmium(II) and lead(II). RESULTS: New
      metal(II) complexes of the polyether ionophorous antibiotic salinomycin with
      Cd(II) and Pb(II) ions were prepared and structurally characterized by IR, FAB-MS
      and NMR techniques. The spectroscopic information and elemental analysis data
      reveal that sodium salinomycin (SalNa) undergoes a reaction with heavy metal(II)
      ions to form [Cd(Sal)2(H2O)2] (1) and [Pb(Sal)(NO3)] (2), respectively.
      Abstraction of sodium ions from the cavity of the antibiotic is occurring during
      the complexation reaction. Salinomycin coordinates with cadmium(II) ions as a
      bidentate monoanionic ligand through the deprotonated carboxylic moiety and one
      of the hydroxyl groups to yield 1. Two salinomycin anions occupy the equatorial
      plane of the Cd(II) center, while two water molecules take the axial positions of
      the inner coordination sphere of the metal(II) cation. Complex 2 consists of
      monoanionic salinomycin acting in polydentate coordination mode in a molar ratio
      of 1: 1 to the metal ion with one nitrate ion for charge compensation.
      CONCLUSION: The formation of the salinomycin heavy metal(II) complexes indicates
      a possible antidote activity of the ligand in case of chronic/acute intoxications
      likely to occur in the stock farming.

PMID- 21906281
TI  - Toxicity report of once weekly radiation therapy for low-risk prostate
      adenocarcinoma: preliminary results of a phase I/II trial.
AB  - BACKGROUND: Increasing clinical data supports a low alpha/beta ratio for prostate
      adenocarcinoma, potentially lower than that of surrounding normal tissues. A
      hypofractionated, weekly radiation therapy (RT) schedule should result in
      improved tumour control, reduced acute toxicity, and similar or decreased late
      effects. We report the toxicity profile of such treatment. MATERIALS AND METHODS:
      We conducted a multi-institution phase I/II trial of three-dimensional conformal
      radiation therapy (3D-CRT) for favourable-risk prostate cancer (T1a-T2a, Gleason
      <= 6 and PSA < 10 ng/ml). RT consisted of 45 Gy in nine 5 Gy fractions, once
      weekly. Primary end-points were feasibility and late gastrointestinal (GI)
      toxicity (RTOG scale), while secondary end-points included acute GI toxicity,
      acute and late genitourinary (GU) toxicity, biochemical control, and survival.
      RESULTS: Between 2006 and 2008, 80 patients were treated. No treatment
      interruptions occurred. The median follow-up is 33 months (range: 20-51). Maximal
      grade 1, 2, and 3 acute (< 3 months) GU toxicity was 29%, 31% and 5% respectively
      (no grade 4). Acute GI grade 1 toxicity was reported in 30% while grade 2
      occurred in 14% (no grade 3 or 4). Crude late grade >= 3 toxicity rates at 31
      months were 2% for both GU and GI toxicity. Cumulative late grade >= 3 GI
      toxicity at 3 years was 11%. Two patients had PSA failure according to the
      Phoenix definition. The three-year actuarial biochemical control rate is 97%.
      CONCLUSIONS: Weekly RT with 45 Gy in 9 fractions is feasible and results in
      comparable toxicity. Long term tumour control and survival remain to be assessed.

PMID- 21906283
TI  - Dissemination of Metarhizium anisopliae of low and high virulence by mating
      behavior in Aedes aegypti.
AB  - BACKGROUND: Dengue is a viral disease transmitted by Aedes mosquitoes. It is a
      threat for public health worldwide and its primary vector Aedes aegypti is
      becoming resistant to chemical insecticides. These factors have encouraged
      studies to evaluate entomopathogenic fungi against the vector. Here we evaluated
      mortality, infection, insemination and fecundity rates in A. aegypti females
      after infection by autodissemination with two Mexican strains of Metarhizium
      anisopliae. METHODS: Two M. anisopliae strains were tested: The Ma-CBG-1 least
      virulent (lv), and the Ma-CBG-2 highly virulent (hv) strain. The lv was tested as
      non mosquito-passed (NMP), and mosquito-passed (MP), while the hv was examined
      only as MP version, therefore including the control four treatments were used. In
      the first bioassay virulence of fungal strains towards female mosquitoes was
      determined by indirect exposure for 48 hours to conidia-impregnated paper. In the
      second bioassay autodissemination of fungal conidia from fungus-contaminated
      males to females was evaluated. Daily mortality allowed computation of survival
      curves and calculation of the LT50 by the Kaplan-Meier model. All combinations of
      fungal sporulation and mating insemination across the four treatments were
      analyzed by chi2. The mean fecundity was analyzed by ANOVA and means contrasted
      with the Ryan test. RESULTS: Indirect exposure to conidia allowed a faster rate
      of mortality, but exposure to a fungal-contaminated male was also an effective
      method of infecting female mosquitoes. All females confined with the hv strain
      contaminated male died in fifteen days with a LT50 of 7.57 (+/- 0.45) where the
      control was 24.82 (+/- 0.92). For the lv strain, it was possible to increase
      fungal virulence by passing the strain through mosquitoes. 85% of females exposed
      to hv-contaminated males became infected and of them just 10% were inseminated;
      control insemination was 46%. The hv strain reduced fecundity by up to 99%, and
      the lv strain caused a 40% reduction in fecundity. CONCLUSIONS: The hv isolate
      infringed a high mortality, allowed a low rate of insemination, and reduced
      fecundity to nearly zero in females confined with a fungus-contaminated male.
      This pathogenic impact exerted through sexual transmission makes the hv strain of
      M. anisopliae worthy of further research.

PMID- 21906284
TI  - Implementing a genomic data management system using iRODS in the Wellcome Trust
      Sanger Institute.
AB  - BACKGROUND: Increasingly large amounts of DNA sequencing data are being generated
      within the Wellcome Trust Sanger Institute (WTSI). The traditional file system
      struggles to handle these increasing amounts of sequence data. A good data
      management system therefore needs to be implemented and integrated into the
      current WTSI infrastructure. Such a system enables good management of the IT
      infrastructure of the sequencing pipeline and allows biologists to track their
      data. RESULTS: We have chosen a data grid system, iRODS (Rule-Oriented Data
      management systems), to act as the data management system for the WTSI. iRODS
      provides a rule-based system management approach which makes data replication
      much easier and provides extra data protection. Unlike the metadata provided by
      traditional file systems, the metadata system of iRODS is comprehensive and
      allows users to customize their own application level metadata. Users and IT
      experts in the WTSI can then query the metadata to find and track data.The aim of
      this paper is to describe how we designed and used (from both system and user
      viewpoints) iRODS as a data management system. Details are given about the
      problems faced and the solutions found when iRODS was implemented. A simple use
      case describing how users within the WTSI use iRODS is also introduced.
      CONCLUSIONS: iRODS has been implemented and works as the production system for
      the sequencing pipeline of the WTSI. Both biologists and IT experts can now track
      and manage data, which could not previously be achieved. This novel approach
      allows biologists to define their own metadata and query the genomic data using
      those metadata.

PMID- 21906285
TI  - Deep sequencing-based transcriptome analysis of Plutella xylostella larvae
      parasitized by Diadegma semiclausum.
AB  - BACKGROUND: Parasitoid insects manipulate their hosts' physiology by injecting
      various factors into their host upon parasitization. Transcriptomic approaches
      provide a powerful approach to study insect host-parasitoid interactions at the
      molecular level. In order to investigate the effects of parasitization by an
      ichneumonid wasp (Diadegma semiclausum) on the host (Plutella xylostella), the
      larval transcriptome profile was analyzed using a short-read deep sequencing
      method (Illumina). Symbiotic polydnaviruses (PDVs) associated with ichneumonid
      parasitoids, known as ichnoviruses, play significant roles in host immune
      suppression and developmental regulation. In the current study, D. semiclausum
      ichnovirus (DsIV) genes expressed in P. xylostella were identified and their
      sequences compared with other reported PDVs. Five of these genes encode proteins
      of unknown identity, that have not previously been reported. RESULTS: De novo
      assembly of cDNA sequence data generated 172,660 contigs between 100 and 10000 bp
      in length; with 35% of > 200 bp in length. Parasitization had significant impacts
      on expression levels of 928 identified insect host transcripts. Gene ontology
      data illustrated that the majority of the differentially expressed genes are
      involved in binding, catalytic activity, and metabolic and cellular processes. In
      addition, the results show that transcription levels of antimicrobial peptides,
      such as gloverin, cecropin E and lysozyme, were up-regulated after parasitism.
      Expression of ichnovirus genes were detected in parasitized larvae with 19 unique
      sequences identified from five PDV gene families including vankyrin, viral
      innexin, repeat elements, a cysteine-rich motif, and polar residue rich protein.
      Vankyrin 1 and repeat element 1 genes showed the highest transcription levels
      among the DsIV genes. CONCLUSION: This study provides detailed information on
      differential expression of P. xylostella larval genes following parasitization,
      DsIV genes expressed in the host and also improves our current understanding of
      this host-parasitoid interaction.

PMID- 21906286
TI  - A comparative physical map reveals the pattern of chromosomal evolution between
      the turkey (Meleagris gallopavo) and chicken (Gallus gallus) genomes.
AB  - BACKGROUND: A robust bacterial artificial chromosome (BAC)-based physical map is
      essential for many aspects of genomics research, including an understanding of
      chromosome evolution, high-resolution genome mapping, marker-assisted breeding,
      positional cloning of genes, and quantitative trait analysis. To facilitate
      turkey genetics research and better understand avian genome evolution, a BAC
      based integrated physical, genetic, and comparative map was developed for this
      important agricultural species. RESULTS: The turkey genome physical map was
      constructed based on 74,013 BAC fingerprints (11.9 * coverage) from two
      independent libraries, and it was integrated with the turkey genetic map and
      chicken genome sequence using over 41,400 BAC assignments identified by 3,499
      overgo hybridization probes along with > 43,000 BAC end sequences. The physical
      comparative map consists of 74 BAC contigs, with an average contig size of 13.6
      Mb. All but four of the turkey chromosomes were spanned on this map by three or
      fewer contigs, with 14 chromosomes spanned by a single contig and nine
      chromosomes spanned by two contigs. This map predicts 20 to 27 major
      rearrangements distinguishing turkey and chicken chromosomes, despite up to 40
      million years of separate evolution between the two species. These data elucidate
      the chromosomal evolutionary pattern within the Phasianidae that led to the
      modern turkey and chicken karyotypes. The predominant rearrangement mode involves
      intra-chromosomal inversions, and there is a clear bias for these to result in
      centromere locations at or near telomeres in turkey chromosomes, in comparison to
      interstitial centromeres in the orthologous chicken chromosomes. CONCLUSION: The
      BAC-based turkey-chicken comparative map provides novel insights into the
      evolution of avian genomes, a framework for assembly of turkey whole genome
      shotgun sequencing data, and tools for enhanced genetic improvement of these
      important agricultural and model species.

PMID- 21906287
TI  - Mutation of L-2,3-diaminopropionic acid synthase genes blocks staphyloferrin B
      synthesis in Staphylococcus aureus.
AB  - BACKGROUND: Staphylococcus aureus synthesizes two siderophores, staphyloferrin A
      and staphyloferrin B, that promote iron-restricted growth. Previous work on the
      biosynthesis of staphyloferrin B has focused on the role of the synthetase
      enzymes, encoded from within the sbnA-I operon, which build the siderophore from
      the precursor molecules citrate, alpha-ketoglutarate and L-2,3-diaminopropionic
      acid. However, no information yet exists on several other enzymes, expressed from
      the biosynthetic cluster, that are thought to be involved in the synthesis of the
      precursors (or synthetase substrates) themselves. RESULTS: Using mutants carrying
      insertions in sbnA and sbnB, we show that these two genes are essential for the
      synthesis of staphyloferrin B, and that supplementation of the growth medium with
      L-2,3-diaminopropionic acid can bypass the block in staphyloferrin B synthesis
      displayed by the mutants. Several mechanisms are proposed for how the enzymes
      SbnA, with similarity to cysteine synthase enzymes, and SbnB, with similarity to
      amino acid dehydrogenases and ornithine cyclodeaminases, function together in the
      synthesis of this unusual nonproteinogenic amino acid L-2,3-diaminopropionic
      acid. CONCLUSIONS: Mutation of either sbnA or sbnB result in abrogation of
      synthesis of staphyloferrin B, a siderophore that contributes to iron-restricted
      growth of S. aureus. The loss of staphyloferrin B synthesis is due to an
      inability to synthesize the unusual amino acid L-2,3-diaminopropionic acid which
      is an important, iron-liganding component of the siderophore structure. It is
      proposed that SbnA and SbnB function together as an L-Dap synthase in the S.
      aureus cell.

PMID- 21906288
TI  - Improving Cry8Ka toxin activity towards the cotton boll weevil (Anthonomus
      grandis).
AB  - BACKGROUND: The cotton boll weevil (Anthonomus grandis) is a serious insect-pest
      in the Americas, particularly in Brazil. The use of chemical or biological insect
      control is not effective against the cotton boll weevil because of its endophytic
      life style. Therefore, the use of biotechnological tools to produce insect
      resistant transgenic plants represents an important strategy to reduce the damage
      to cotton plants caused by the boll weevil. The present study focuses on the
      identification of novel molecules that show improved toxicity against the cotton
      boll weevil. In vitro directed molecular evolution through DNA shuffling and
      phage display screening was applied to enhance the insecticidal activity of
      variants of the Cry8Ka1 protein of Bacillus thuringiensis. RESULTS: Bioassays
      carried out with A. grandis larvae revealed that the LC50 of the screened mutant
      Cry8Ka5 toxin was 3.15-fold higher than the wild-type Cry8Ka1 toxin. Homology
      modelling of Cry8Ka1 and the Cry8Ka5 mutant suggested that both proteins retained
      the typical three-domain Cry family structure. The mutated residues were located
      mostly in loops and appeared unlikely to interfere with molecular stability.
      CONCLUSIONS: The improved toxicity of the Cry8Ka5 mutant obtained in this study
      will allow the generation of a transgenic cotton event with improved potential to
      control A. grandis.

PMID- 21906289
TI  - Association of HLA-B*5801 allele and allopurinol-induced Stevens Johnson syndrome
      and toxic epidermal necrolysis: a systematic review and meta-analysis.
AB  - BACKGROUND: Despite some studies suggesting a possible association between human
      leukocyte antigen, HLA-B*5801 and allopurinol induced Stevens-Johnson Syndrome
      (SJS) and Toxic Epidermal Necrolysis (TEN), the evidence of association and its
      magnitude remain inconclusive. This study aims to systematically review and meta
      analyze the association between HLA-B*5801 allele and allopurinol-induced
      SJS/TEN. METHODS: A comprehensive search was performed in databases including
      MEDLINE, Pre-MEDLINE, Cochrane Library, EMBASE, International Pharmaceutical
      Abstracts (IPA), CINAHL, PsychInfo, the WHO International, Clinical Trial
      Registry, and ClinicalTrial.gov from their inceptions to June 2011. Only studies
      investigating association between HLA-B*5801 with allopurinol-induced SJS/TEN
      were included. All studies were extracted by two independent authors. The primary
      analysis was the carrier frequency of HLA-B*5801 comparison between allopurinol
      induced SJS/TEN cases and each comparative group. The pooled odds ratios were
      calculated using a random effect model. RESULTS: A total of 4 studies with 55
      SJS/TEN cases and 678 matched-controls (allopurinol-tolerant control) was
      identified, while 5 studies with 69 SJS/TEN cases and 3378 population-controls
      (general population) were found. SJS/TEN cases were found to be significantly
      associated with HLA-B*5801 allele in both groups of studies with matched-control
      (OR 96.60, 95%CI 24.49-381.00, p < 0.001) and population-control (OR 79.28, 95%CI
      41.51-151.35, p < 0.001). Subgroup analysis for Asian and Non-Asian population
      yielded similar findings. CONCLUSION: We found a strong and significant
      association between HLA-B*5801 and allopurinol-induced SJS/TEN. Therefore, HLA
      B*5801 allele screening may be considered in patients who will be treated with
      allopurinol.

PMID- 21906290
TI  - Supplier-induced demand for psychiatric admissions in Northern New England.
AB  - BACKGROUND: The development of hospital service areas (HSAs) using small area
      analysis has been useful in examining variation in medical and surgical care;
      however, the techniques of small area analysis are underdeveloped in
      understanding psychiatric admission rates. We sought to develop these techniques
      in order to understand the relationship between psychiatric bed supply and
      admission rates in Northern New England. Our primary hypotheses were that there
      would be substantial variation in psychiatric admission across geographic
      settings and that bed availability would be positively correlated with admission
      rates, reflecting a supplier-induced demand phenomenon. Our secondary hypothesis
      was that the construction of psychiatric HSAs (PHSAs) would yield more meaningful
      results than the use of existing general medical hospital service areas. METHODS:
      To address our hypotheses, we followed a four-step analytic process: 1) we used
      small area analytic techniques to define our PHSAs, 2) we calculated the
      localization index for PHSAs and compared that to the localization index for
      general medical HSAs, 3) we used the number of psychiatric hospital beds, the
      number of psychiatric admissions, and census data to calculate population-based
      bed-supply and psychiatric admission rates for each PHSA, and 4) we correlated
      population-based admission rates to population-based psychiatric bed supply.
      RESULTS: The admission rate for psychiatric diagnosis varied considerably among
      the PHSAs, with rates varying from 2.4 per 100,000 in Portsmouth, NH to 13.4 per
      100,000 in Augusta, ME. There was a positive correlation of 0.71 between a PHSA's
      supply of beds and admission rate. Using our PSHAs produced a substantially
      higher localization index than using general medical hospital services areas
      (0.69 vs. 0.23), meaning that our model correctly predicted geographic
      utilization at three times the rate of the existing model. CONCLUSIONS: The
      positive correlation between admission and bed supply suggests that psychiatric
      bed availability may partially explain the variation in admission rates.
      Development of PHSAs, rather than relying on the use of established general
      medical HSAs, improves the relevance and accuracy of small area analysis in
      understanding mental health services utilization.

PMID- 21906291
TI  - Factors associated with default from treatment among tuberculosis patients in
      Nairobi province, Kenya: a case control study.
AB  - BACKGROUND: Successful treatment of tuberculosis (TB) involves taking anti
      tuberculosis drugs for at least six months. Poor adherence to treatment means
      patients remain infectious for longer, are more likely to relapse or succumb to
      tuberculosis and could result in treatment failure as well as foster emergence of
      drug resistant tuberculosis. Kenya is among countries with high tuberculosis
      burden globally. The purpose of this study was to determine the duration
      tuberculosis patients stay in treatment before defaulting and factors associated
      with default in Nairobi. METHODS: A Case-Control study; Cases were those who
      defaulted from treatment and Controls those who completed treatment course
      between January 2006 and March 2008. All (945) defaulters and 1033 randomly
      selected controls from among 5659 patients who completed treatment course in 30
      high volume sites were enrolled. Secondary data was collected using a facility
      questionnaire. From among the enrolled, 120 cases and 154 controls were randomly
      selected and interviewed to obtain primary data not routinely collected. Data was
      analyzed using SPSS and Epi Info statistical software. Univariate and
      multivariate logistic regression analysis to determine association and Kaplan
      Meier method to determine probability of staying in treatment over time were
      applied. RESULTS: Of 945 defaulters, 22.7% (215) and 20.4% (193) abandoned
      treatment within first and second months (intensive phase) of treatment
      respectively. Among 120 defaulters interviewed, 16.7% (20) attributed their
      default to ignorance, 12.5% (15) to traveling away from treatment site, 11.7%
      (14) to feeling better and 10.8% (13) to side-effects. On multivariate analysis,
      inadequate knowledge on tuberculosis (OR 8.67; 95% CI 1.47-51.3), herbal
      medication use (OR 5.7; 95% CI 1.37-23.7), low income (OR 5.57, CI 1.07-30.0),
      alcohol abuse (OR 4.97; 95% CI 1.56-15.9), previous default (OR 2.33; 95% CI 1.16
      4.68), co-infection with Human immune-deficient Virus (HIV) (OR 1.56; 95% CI 1.25
      1.94) and male gender (OR 1.43; 95% CI 1.15-1.78) were independently associated
      with default. CONCLUSION: The rate of defaulting was highest during initial two
      months, the intensive phase of treatment. Multiple factors were attributed by
      defaulting patients as cause for abandoning treatment whereas several were
      independently associated with default. Enhanced patient pre-treatment counseling
      and education about TB is recommended.

PMID- 21906292
TI  - Semiquantitative assessment of subchondral bone marrow edema-like lesions and
      subchondral cysts of the knee at 3T MRI: a comparison between intermediate
      weighted fat-suppressed spin echo and Dual Echo Steady State sequences.
AB  - BACKGROUND: Choice of appropriate MR pulse sequence is important for any research
      studies using imaging-derived data. The aim of this study was to compare
      semiquantitative assessment of subchondral bone marrow edema-like lesions and
      subchondral cysts using intermediate-weighted (IW) fat-suppressed (fs) spin echo
      and Dual Echo Steady State (DESS) sequences on 3 T MRI. METHODS: Included were
      201 subjects aged 35-65 with frequent knee pain. 3T MRI was performed with the
      same sequence protocol as in the Osteoarthritis Initiative (OAI). In a primary
      reading subchondral bone marrow edema-like lesions were assessed according to the
      WORMS system. Two hundred subregions with such lesions were randomly chosen. The
      extent of subchondral bone marrow edema-like lesions was re-evaluated separately
      using sagittal IW fs and DESS sequences according to WORMS. Lesion size and
      confidence of the differentiation between subchondral bone marrow edema-like
      lesions and subchondral cysts located within or adjacent to them was rated from 0
      to 3. Wilcoxon signed-rank tests and chi-square statistics were used to examine
      differences between the two sequences. RESULTS: Of 200 subchondral bone marrow
      edema-like lesions detected by IW fs sequence, 93 lesions (46.5%) were not
      depicted by the DESS sequence. The IW fs sequence depicted subchondral bone
      marrow edema-like lesions to a larger extent than DESS (p < 0.0001), and the
      opposite was true for subchondral cysts. Confidence scores for differentiation of
      the two types of lesions were not significantly different between the two
      sequences. CONCLUSIONS: In direct comparison the IW fs sequence depicts more
      subchondral bone marrow edema-like lesions and better demonstrate the extent of
      their maximum size. The DESS sequence helps in the differentiation of subchondral
      bone marrow edema-like lesions and subchondral cysts. The IW fs sequence should
      be used for determination of lesion extent whenever the size of subchondral bone
      marrow edema-like lesions is the focus of attention.

PMID- 21906293
TI  - Is the impact of hospital performance data greater in patients who have compared
      hospitals?
AB  - BACKGROUND: Public information on average has limited impact on patients'
      hospital choice. However, the impact may be greater in consumers who have
      compared hospitals prior to their hospital choice. We therefore assessed whether
      patients who have compared hospitals based their hospital choice mainly on public
      information, rather than e.g. advice of their general practitioner and consider
      other information important than patients who have not compared hospitals.
      METHODS: 337 new surgical patients completed an internet-based questionnaire.
      They were asked whether they had compared hospitals prior to their hospital
      choice and which factors influenced their choice. They were also asked to select
      between four and ten items of hospital information (total: 41 items) relevant for
      their future hospital choice. These were subsequently used in a hospital choice
      experiment in which participants were asked to compare hospitals in an Adaptive
      Choice-Based Conjoint analysis to estimate which of the hospital characteristics
      had the highest Relative Importance (RI). RESULTS: Patients who have compared
      hospitals more often used public information for their hospital choice than
      patients who have not compared hospitals (12.7% vs. 1.5%, p < 0.001). However,
      they still mostly relied on their own (47.9%) and other people's experiences
      (31%) rather than to base their decision on public information. Both groups
      valued physician's expertise (RI 20.2 [16.6-24.8] in patients comparing hospitals
      vs. 16.5 [14.2-18.8] in patients not comparing hospitals) and waiting time (RI
      15.1 [10.7-19.6] vs. 15.6 [13.2-17.9] respectively) as most important public
      information. Patients who have compared hospitals assigned greater importance to
      information on wound infections (p = 0.010) and respect for patients (p = 0.022),
      but lower importance to hospital distance (p = 0.041). CONCLUSION: Public
      information has limited impact on patient's hospital choice, even in patients who
      have actually compared hospitals prior to hospital choice.

PMID- 21906294
TI  - diArk 2.0 provides detailed analyses of the ever increasing eukaryotic genome
      sequencing data.
AB  - BACKGROUND: Nowadays, the sequencing of even the largest mammalian genomes has
      become a question of days with current next-generation sequencing methods. It
      comes as no surprise that dozens of genome assemblies are released per months
      now. Since the number of next-generation sequencing machines increases worldwide
      and new major sequencing plans are announced, a further increase in the speed of
      releasing genome assemblies is expected. Thus it becomes increasingly important
      to get an overview as well as detailed information about available sequenced
      genomes. The different sequencing and assembly methods have specific
      characteristics that need to be known to evaluate the various genome assemblies
      before performing subsequent analyses. RESULTS: diArk has been developed to
      provide fast and easy access to all sequenced eukaryotic genomes worldwide.
      Currently, diArk 2.0 contains information about more than 880 species and more
      than 2350 genome assembly files. Many meta-data like sequencing and read-assembly
      methods, sequencing coverage, GC-content, extended lists of alternatively used
      scientific names and common species names, and various kinds of statistics are
      provided. To intuitively approach the data the web interface makes extensive
      usage of modern web techniques. A number of search modules and result views
      facilitate finding and judging the data of interest. Subscribing to the RSS feed
      is the easiest way to stay up-to-date with the latest genome data. CONCLUSIONS:
      diArk 2.0 is the most up-to-date database of sequenced eukaryotic genomes
      compared to databases like GOLD, NCBI Genome, NHGRI, and ISC. It is different in
      that only those projects are stored for which genome assembly data or
      considerable amounts of cDNA data are available. Projects in planning stage or in
      the process of being sequenced are not included. The user can easily search
      through the provided data and directly access the genome assembly files of the
      sequenced genome of interest. diArk 2.0 is available at http://www.diark.org.

PMID- 21906295
TI  - Reference genes for quantitative reverse transcription-polymerase chain reaction
      expression studies in wild and cultivated peanut.
AB  - BACKGROUND: Wild peanut species (Arachis spp.) are a rich source of new alleles
      for peanut improvement. Plant transcriptome analysis under specific experimental
      conditions helps the understanding of cellular processes related, for instance,
      to development, stress response, and crop yield. The validation of these studies
      has been generally accomplished by quantitative reverse transcription-polymerase
      chain reaction (qRT-PCR) which requires normalization of mRNA levels among
      samples. This can be achieved by comparing the expression ratio between a gene of
      interest and a reference gene which is constitutively expressed. Nowadays there
      is a lack of appropriate reference genes for both wild and cultivated Arachis.
      The identification of such genes would allow a consistent analysis of qRT-PCR
      data and speed up candidate gene validation in peanut. RESULTS: A set of ten
      reference genes were analyzed in four Arachis species (A. magna; A. duranensis;
      A. stenosperma and A. hypogaea) subjected to biotic (root-knot nematode and leaf
      spot fungus) and abiotic (drought) stresses, in two distinct plant organs (roots
      and leaves). By the use of three programs (GeNorm, NormFinder and BestKeeper) and
      taking into account the entire dataset, five of these ten genes, ACT1 (actin
      depolymerizing factor-like protein), UBI1 (polyubiquitin), GAPDH (glyceraldehyde
      3-phosphate dehydrogenase), 60S (60S ribosomal protein L10) and UBI2
      (ubiquitin/ribosomal protein S27a) emerged as top reference genes, with their
      stability varying in eight subsets. The former three genes were the most stable
      across all species, organs and treatments studied. CONCLUSIONS: This first in
      depth study of reference genes validation in wild Arachis species will allow the
      use of specific combinations of secure and stable reference genes in qRT-PCR
      assays. The use of these appropriate references characterized here should improve
      the accuracy and reliability of gene expression analysis in both wild and
      cultivated Arachis and contribute for the better understanding of gene expression
      in, for instance, stress tolerance/resistance mechanisms in plants.

PMID- 21906296
TI  - The use of HaloTag-based technology in flow and laser scanning cytometry analysis
      of live and fixed cells.
AB  - BACKGROUND: Combining the technologies of protein tag labeling and optical
      microscopy allows sensitive analysis of protein function in cells. FINDINGS:
      Here, we describe development of applications using protein tag technology
      (HaloTag (HT)-based) for flow and laser scanning cytometry (LSC). Cell lines,
      expressing recombinant surface beta1-integrin-HT and HT-p65 fusion protein, and a
      CD4 T cell line (Jurkat) infected with human immunodeficiency virus type 1 (HIV
      1) reporter virus expressing the unfused HT (HIV-1Lai-Halo), were stained with
      different HT ligands and successfully detected by flow cytometers equipped with
      488 and 561 nm lasers as well as a laser scanning cytometer (equipped with 488
      and 405 nm lasers) alone or combined with cell cycle and viability markers.
      CONCLUSIONS: Use of HT technology for cytometric applications has advantages over
      its use in microscopy as it allows for the statistical measurement of protein
      expression levels in individual cells within a heterogeneous cell population in
      combination with cell cycle analysis. Another advantage is the ability of the
      HaloTag to withstand long fixation and high concentration of fixative, which can
      be useful in research of infectious agents like HIV and/or mycobacteria.

PMID- 21906297
TI  - Markedly lower follow-up rate after liver biopsy in patients with non-alcoholic
      fatty liver diseases than those with viral hepatitis in Japan.
AB  - BACKGROUND: Patients with non-alcoholic fatty liver diseases (NAFLD) are
      recommended to have periodic follow-up exams because these patients are at
      increased risk of the presence of non-alcoholic steatohepatitis (NASH), which can
      lead to cirrhosis or hepatocellular carcinoma. We investigated the follow-up
      status of NAFLD patients after a liver biopsy examination. METHODS: We compared
      the follow-up rates of NAFLD patients who had received an ultrasonography-guided
      liver biopsy and patients who had received a liver biopsy for chronic viral
      hepatitis (hepatitis B or C). RESULTS: The 1- and 3-year follow-up rates after
      the liver biopsy were 92.7% and 88.3% for patients with chronic HBV infection,
      and 93.4% and 88.2% for patients with chronic HCV infection, respectively. In
      contrast, the follow-up rates for NAFLD patients were 77.6% and 49.9%,
      respectively, which were significantly lower than those of patients with chronic
      viral hepatitis (p < 0.0001). Among NAFLD patients, the respective 1- and 3-year
      follow-up rates were 73.0% and 44.6% for patients with simple steatosis and 80.0%
      and 52.4% for patients with NASH based on a pathologic diagnosis, without
      significant difference between these two subgroups (p = 0.5202). CONCLUSIONS: The
      outpatient-based follow-up rate after a liver biopsy was significantly lower in
      NAFLD patients compared to patients with chronic viral hepatitis, regardless of
      the presence of NASH. It is important to determine how to maintain regular
      hospital visits for NAFLD patients, preventing patient attrition.

PMID- 21906298
TI  - The effect of competition on heart rate during kart driving: A field study.
AB  - BACKGROUND: Both the act of competing, which can create a kind of mental stress,
      and participation in motor sports, which induces physical stress from intense g
      forces, are known to increase heart rate dramatically. However, little is known
      about the specific effect of competition on heart rate during motor sports,
      particularly during four-wheel car driving. The goal of this preliminary study,
      therefore, was to investigate whether competition increases heart rate under such
      situations. FINDINGS: The participants drove an entry-level formula kart during
      two competitive races and during solo driving against the clock while heart rate
      and g-forces were measured. Analyses showed that heart rate values during the
      races (168.8 beats/min) were significantly higher than those during solo driving
      (140.9 beats/min) and rest (75.1 beats/min). CONCLUSIONS: The results of this
      preliminary study indicate that competition heightens heart rate during four
      wheel car driving. Kart drivers should be concerned about maintaining good health
      and developing physical strength.

PMID- 21906299
TI  - Birth defects in newborns and stillborns: an example of the Brazilian reality.
AB  - BACKGROUND: This study constitutes a clinical and genetic study of all newborn
      and stillborn infants with birth defects seen in a period of one year in a
      medical school hospital located in Brazil. The aims of this study were to
      estimate the incidence, causes and consequences of the defects. METHODS: For all
      infants we carried out physical assessment, photographic records, analysis of
      medical records and collection of additional information with the family, besides
      the karyotypic analysis or molecular tests in indicated cases. RESULT: The
      incidence of birth defects was 2.8%. Among them, the etiology was identified in
      73.6% (ci95%: 64.4-81.6%). Etiology involving the participation of genetic
      factors single or associated with environmental factors) was more frequent 94.5%,
      ci95%: 88.5-98.0%) than those caused exclusively by environmental factors
      (alcohol in and gestational diabetes mellitus). The conclusive or presumed
      diagnosis was possible in 85% of the cases. Among them, the isolated congenital
      heart disease (9.5%) and Down syndrome (9.5%) were the most common, followed by
      gastroschisis (8.4%), neural tube defects (7.4%) and clubfoot (5.3%). Maternal
      age, parental consanguinity, exposure to teratogenic agents and family
      susceptibility were some of the identified risk factors. The most common observed
      consequences were prolonged hospital stays and death. CONCLUSIONS: The current
      incidence of birth defects among newborns and stillbirths of in our population is
      similar to those obtained by other studies performed in Brazil and in other
      underdeveloped countries. Birth defects are one of the major causes leading to
      lost years of potential life. The study of birth defects in underdeveloped
      countries should continue. The identification of incidence, risk factors and
      consequences are essential for planning preventive measures and effective
      treatments.

PMID- 21906300
TI  - Pharmacokinetic and technical comparison of Sandostatin(r) LAR(r) and other
      formulations of long-acting octreotide.
AB  - BACKGROUND: Sandostatin(r) LAR(r) (Novartis Pharma AG) is a long-acting
      repeatable formulation of the somatostatin analogue octreotide, the safety and
      efficacy of which has been established through 15 years of clinical experience.
      Recently, other formulations of octreotide using polymer poly(lactic-co-glycolic
      acid) technology have been developed. This study compares the composition and
      pharmacokinetic (PK) profile of Sandostatin LAR with three other versions of the
      depot delivery system (formulations A, B and C, available in selected countries).
      FINDINGS: Sandostatin LAR exhibited a characteristic concentration-time profile
      with a limited initial release of octreotide ('burst'), an erosion phase from
      weeks 3-5, and a slowly declining concentration to day 52. The PK profiles of
      formulations A and B were characterized by a large initial burst during days 0-2,
      with up to 41% of the overall area under the plasma-concentration time curve
      achieved. Low and variable octreotide concentrations were observed during the
      microparticle erosion phase (days 2-62 [day 82 formulation C]) for formulations
      A, B and C. Sandostatin LAR microparticles are spherical in shape with an average
      diameter of approximately 50 MUm, determined by scanning electron microscopy
      evaluation. Formulation A had smaller, irregular microparticles, and formulations
      B and C exhibited a large range of particle diameters (< 20 to > 100 MUm).
      Inductively coupled plasma-optical emission spectroscopy detected a high tin
      content of 104 mg/kg in formulation B, the presence of which may suggest
      inadequate purification following polymer synthesis using tin(II)-octoate as
      catalyst. PK profiles for formulations A, B and C after a single intramuscular
      injection of 4 mg/kg in male New Zealand rabbits differed markedly from the PK
      profile of Sandostatin LAR. CONCLUSIONS: Clear differences were seen between
      Sandostatin LAR and formulations A, B and C, including variations in
      microparticle size, shape and impurity content. Considering the significant
      differences in the octreotide release profile between Sandostatin LAR and the
      other formulations, the safety and efficacy of the other formulations cannot be
      inferred from the Sandostatin LAR efficacy and safety profile; each of these
      other formulations should be assessed accordingly.

PMID- 21906301
TI  - Lactogenic differentiation of HC11 cells is not accompanied by downregulation of
      AP-2 transcription factor genes.

PMID- 21906302
TI  - Portion control for the treatment of obesity in the primary care setting.
AB  - BACKGROUND: The increasing prevalence of obesity is a significant health threat
      and a major public health challenge. A critical need exists to develop and
      evaluate practical methods for the treatment of obesity in the clinical setting.
      One of the factors contributing to the obesity epidemic is food portion sizes.
      Limited data are available on the efficacy of visual or tactile devices designed
      to enhance patient understanding and control of portion sizes. A portion control
      plate is a commercially-available product that can provide visual cues of portion
      size and potentially contribute to weight loss by enhancing portion size control
      among obese patients. This tool holds promise as a useful adjunct to dietary
      counseling. Our objective was to evaluate a portion control intervention
      including dietary counseling and a portion control plate to facilitate weight
      loss among obese patients in a primary care practice. FINDINGS: We randomized 65
      obese patients [body mass index (BMI) >= 30 and < 40] to an intervention
      including counseling by a dietitian incorporating a portion control plate or to
      usual care. Following initial consultation, patients in the intervention arm were
      contacted at 1, 3, and 5 months by the dietician for brief follow-up counseling.
      Usual care subjects received instructional handouts on diet and exercise. Forty
      two (65%) subjects returned to have weight assessed at 6 months. Subjects in the
      portion control intervention had a greater percentage change (+/- SD) in weight
      from baseline at 3 months (-2.4% +/- 3.7% vs. -0.5% +/- 2.2%; p = 0.041) and a
      non significant trend in weight change from baseline at 6 months (-2.1% +/- 3.8%
      vs. -0.7% +/- 3.7%; p = 0.232) compared with usual care. Nearly one-half of
      patients assigned to the portion control intervention who completed the study
      reported the overall intervention was helpful and the majority would recommend it
      to others. CONCLUSIONS: Our findings suggest that a portion control intervention
      incorporating dietary counseling and a portion control plate may be effective for
      enhancing weight loss among obese subjects. A portion control intervention
      deserves further evaluation as a weight control strategy in the primary care
      setting. TRIAL REGISTRATION: Current controlled trials NCT01451554.

PMID- 21906303
TI  - Intensive care unit course of infants and children after cranial vault
      reconstruction for craniosynostosis.
AB  - BACKGROUND: Craniosynostosis (CSS) results from the premature closure of one or
      more cranial sutures, leading to deformed calvaria at birth. It is a common
      finding in children with an incidence of one in 2000 births. Surgery is required
      in order to release the synostotic constraint and promote normal calvaria growth.
      Cranial vault remodeling is the surgical approach to CSS repair at our
      institution and it involves excision of the frontal, parietal, and occipital
      bones. The purpose of this article is to describe the post-operative course of
      infants and children admitted to our PICU after undergoing cranial vault
      remodeling for primary CSS. FINDINGS: Complete data was available for analyses in
      only 82 patients, 44 males (M) and 38 females (F); M: F ratio was 1:1.2. Patients
      (pts) age in months (mo) ranged from 2 mo to 132 mo, mean 18.2 +/--24.9 mo and
      weights (wt) ranged from 4.7 kg to 31.4 kg, mean 10.24 +/- 5.5 Kg.. Duration of
      surgery (DOS) ranged from 70 minutes to 573 minutes mean 331.6 +/- 89.0 minutes.
      No significant correlation exist between duration of surgery, suture category,
      patient's age or use of blood products (P > 0.05). IOP blood loss was higher in
      older pts (P < 0.05) and it correlates with body temperature in the PICU (P <
      .0001). Post-op use of FFP correlated with intra-operative PRBC transfusion (P <
      0.0001). More PRBC was transfused within 12 hrs-24 hrs in PICU compared to other
      time periods (P < 0.05). LOS in PICU was < 3 days in 68% and > 3 days in 32%. Pts
      with fever had prolonged LOS (P < 0. 05); re-intubation rate was 2.4% and MVD
      were 1.83 days. Repeat operation for poor cosmetic results occurred in 9.7% of
      pts. CONCLUSIONS: Post-op morbidities from increased use of blood products can be
      minimized if cranial vault remodeling is done at a younger age in patients with
      primary CSS. PICU length of stay is determined in part by post-op pyrexia and it
      can be reduced if extensive evaluations of post-op fever are avoided.

PMID- 21906304
TI  - Aortic dissection at the University hospital of the West Indies: A 20-year
      clinicopathological study of autopsy cases.
AB  - BACKGROUND: An autopsy study of aortic dissection (AD) at our institution was
      previously reported. In the approximately 20 years since then, however, many
      aspects of diagnosis and treatment of this disease have changed, with a fall in
      mortality reported in many centers around the world. An impression amongst our
      pathologists that, there might be an increase in the prevalence of AD in the
      autopsy service at our hospital, since that earlier report, led to this repeated
      study, in an attempt to validate that notion. We also sought to identify any
      changes in clinicopathological features between the two series or any occurring
      during this study period itself. FINDINGS: All cases of AD identified at autopsy,
      during the 20-year period since the conclusion of the last study, were collected
      and pertinent clinical and pathological data were analyzed and compared, both
      within the two decades of this study period and against the results of the last
      study.Fifty-six cases comprised this study group including 36 males and 20
      females, with a mean age of 63.9 years. There were, more patients in the second
      decade (n = 33; 59%) compared with the first decade (n = 23; 41%). Hypertension
      as a risk factor was identified in 52 (93%) cases and rupture occurred in 49
      (88%) cases. A clinical diagnosis of AD was considered prior to surgery or
      autopsy in 25 (45%) cases overall, more during the second decade. Surgery was
      attempted in 25% of all cases with an increase in the second decade compared with
      the first. CONCLUSIONS: Compared with the earlier review, a variety of changes in
      the profile of patients with AD in the autopsy service has been noted, including
      a reversal in the female predominance seen previously. Other observations include
      an increase in cases where the correct clinical diagnosis was considered and in
      which surgical treatment was attempted, changes also evident when the second
      decade of the present study was compared with the earlier decade. Overall, there
      were many positive trends. However, areas that could still be improved include an
      increased index of suspicion for the diagnosis of AD and perhaps in the
      initiation of treatment, earlier, in those cases where the correct diagnosis was
      considered.

PMID- 21906305
TI  - The BrainMap strategy for standardization, sharing, and meta-analysis of
      neuroimaging data.
AB  - BACKGROUND: Neuroimaging researchers have developed rigorous community data and
      metadata standards that encourage meta-analysis as a method for establishing
      robust and meaningful convergence of knowledge of human brain structure and
      function. Capitalizing on these standards, the BrainMap project offers databases,
      software applications, and other associated tools for supporting and promoting
      quantitative coordinate-based meta-analysis of the structural and functional
      neuroimaging literature. FINDINGS: In this report, we describe recent technical
      updates to the project and provide an educational description for performing meta
      analyses in the BrainMap environment. CONCLUSIONS: The BrainMap project will
      continue to evolve in response to the meta-analytic needs of biomedical
      researchers in the structural and functional neuroimaging communities. Future
      work on the BrainMap project regarding software and hardware advances are also
      discussed.

PMID- 21906306
TI  - Chlamydia in canine or feline coronary arteriosclerotic lesions.
AB  - BACKGROUND: There are numerous reports linking Chlamydia infection to human
      coronary atherosclerosis. However, there is a lack of data regarding this
      correlation in dogs and cats, and there are no reports investigating coronary
      arteriosclerosis and Chlamydia in these species. The aim of the present study was
      to examine whether there is a correlation between canine and feline spontaneous
      atherosclerosis or arteriosclerosis and the presence of Chlamydia. Archived
      histopathological samples of dogs (n = 16) and cats (n = 13) with findings of
      atherosclerosis or arteriosclerosis in heart tissue were examined for the
      presence of Chlamydiaceae using real-time PCR, ArrayTube Microarray and
      immunohistochemistry. Additionally, arteriosclerotic lesions of all cases were
      histologically classified and graded. RESULTS: Both canine atherosclerotic cases,
      and all 14 canine arteriosclerotic cases were negative for Chlamydia. Only one of
      the 13 arteriosclerotic feline cases was positive for Chlamydia by real-time PCR,
      revealing C. abortus by ArrayTube Microarray. To our knowledge, this is the first
      description of C. abortus in a cat. Overall, the type and grade of canine and
      feline arteriosclerotic lesions revealed similarities, and were predominantly
      moderate and hyperplastic. CONCLUSIONS: These findings suggest that there is no
      obvious correlation between canine and feline coronary arteriosclerosis and the
      presence of Chlamydia. In order to draw final conclusions about the correlation
      between Chlamydia and canine atherosclerosis, examination of more samples is
      required.

PMID- 21906307
TI  - HOX genes in ovarian cancer.
AB  - The HOX genes are a family of homeodomain-containing transcription factors that
      determine cellular identity during development. Here we review a number of recent
      studies showing that HOX genes are strongly expressed in ovarian cancer, and that
      in some cases the expression of specific HOX genes is sufficient to confer a
      particular identity and phenotype upon cancer cells. We also review the recent
      advances in elucidating the different functions of HOX genes in ovarian cancer. A
      literature search was performed using the search terms HOX genes (including
      specific HOX genes), ovarian cancer and oncogenesis. Articles were accessed
      through searches performed in ISI Web of Knowledge, PubMed and ScienceDirect.
      Taken together, these studies have shown that HOX genes play a role in the
      oncogenesis of ovarian cancer and function in the inhibition of apoptosis, DNA
      repair and enhanced cell motility. The function of HOX genes in ovarian cancer
      oncogenesis supports their potential role as prognostic and diagnostic markers,
      and as therapeutic targets in this disease.

PMID- 21906308
TI  - Adenovirus-mediated delivery of bFGF small interfering RNA reduces STAT3
      phosphorylation and induces the depolarization of mitochondria and apoptosis in
      glioma cells U251.
AB  - Glioblastoma multiforme (GBM) carries a dismal prognosis primarily due to its
      aggressive proliferation in the brain regulated by complex molecular mechanisms.
      One promising molecular target in GBM is over-expressed basic fibroblast growth
      factor (bFGF), which has been correlated with growth, progression, and
      vascularity of human malignant gliomas. Previously, we reported significant
      antitumor effects of an adenovirus-vector carrying bFGF small interfering RNA (Ad
      bFGF-siRNA) in glioma in vivo and in vitro. However, its mechanisms are unknown.
      Signal transducer and activator of transcription 3 (STAT3) is constitutively
      active in GBM and correlates positively with the glioma grades. In addition, as a
      specific transcription factor, STAT3 serves as the convergent point of various
      signaling pathways activated by multiple growth factors and/or cytokines.
      Therefore, we hypothesized that the proliferation inhibition and apoptosis
      induction by Ad-bFGF-siRNA may result from the interruption of STAT3
      phosphorylation. In the current study, we found that in glioma cells U251, Ad
      bFGF-siRNA impedes the activation of ERK1/2 and JAK2, but not Src, decreases IL-6
      secretion, reduces STAT3 phosphorylation, decreases the levels of downstream
      molecules CyclinD1 and Bcl-xl, and ultimately results in the collapse of
      mitochondrial membrane potentials as well as the induction of mitochondrial
      related apoptosis. Our results offer a potential mechanism for using Ad-bFGF
      siRNA as a gene therapy for glioma. To our knowledge, it is the first time that
      the bFGF knockdown using adenovirus-mediated delivery of bFGF siRNA and its
      potential underlying mechanisms are reported. Therefore, this finding may open
      new avenues for developing novel treatments against GBM.

PMID- 21906309
TI  - Mining the diseasome.

PMID- 21906311
TI  - Ultra-long metal nanowire arrays on solid substrate with strong bonding.
AB  - Ultra-long metal nanowire arrays with large circular area up to 25 mm in
      diameter were obtained by direct electrodeposition on metalized Si and glass
      substrates via a template-based method. Nanowires with uniform length up to 30
      MUm were obtained. Combining this deposition process with lithography technology,
      micrometre-sized patterned metal nanowire array pads were successfully fabricated
      on a glass substrate. Good adhesion between the patterned nanowire array pads and
      the substrate was confirmed using scanning acoustic microscopy characterization.
      A pull-off tensile test showed strong bonding between the nanowires and the
      substrate. Conducting atomic force microscopy (C-AFM) measurements showed that
      approximately 95% of the nanowires were electrically connected with the
      substrate, demonstrating its viability to use as high-density interconnect.

PMID- 21906310
TI  - Chemotherapy in advanced bladder cancer: current status and future.
AB  - Bladder cancer occurs in the majority of cases in males. It represents the
      seventh most common cancer and the ninth most common cause of cancer deaths for
      men. Transitional cell carcinoma is the most predominant histological type.
      Bladder cancer is highly chemosensitive. In metastatic setting, chemotherapy
      based on cisplatin should be considered as standard treatment of choice for
      patients with good performance status (0-1) and good renal function-glomerular
      filtration rate (GFR) > 60 mL/min. The standard treatment is based on cisplatin
      chemotherapy regimens type MVAC, HD-MVAC, gemcitabine plus cisplatin (GC) or dose
      dense GC. In unfit patients, carboplatin based regimes; gemcitabine plus
      carboplatin or methotrexate plus carboplatin plus vinblastine (MCAVI) are
      reasonable options. The role of targeted therapies when used alone, or in
      combination with chemotherapy, or in maintenance, was evaluated; targeting
      angiogenesis seem to be very promising. The purpose of this literature review is
      to highlight the role of chemotherapy in the management of advanced transitional
      cell carcinoma of the bladder.

PMID- 21906312
TI  - Clinical relevance of "withdrawal therapy" as a form of hormonal manipulation for
      breast cancer.
AB  - BACKGROUND: It has been shown in in-vitro experiments that "withdrawal" of
      tamoxifen inhibits growth of tumor cells. However, evidence is scarce when this
      is extrapolated into clinical context. We report our experience to verify the
      clinical relevance of "withdrawal therapy". METHODS: Breast cancer patients since
      1998 who fulfilled the following criteria were selected from the departmental
      database and the case-notes were retrospectively reviewed: (1) estrogen receptor
      positive, operable primary breast cancer in elderly (age > 70 years), locally
      advanced or metastatic breast cancer; (2) disease deemed suitable for treatment
      by hormonal manipulation; (3) disease assessable by UICC criteria; (4) received
      "withdrawal" from a prior endocrine agent as a form of therapy; (5) on
      "withdrawal therapy" for >= 6 months unless they progressed prior. RESULTS:
      Seventeen patients with median age of 84.3 (53.7-92.5) had "withdrawal therapy"
      as second to tenth line of treatment following prior endocrine therapy using
      tamoxifen (n = 10), an aromatase inhibitor (n = 5), megestrol acetate (n = 1) or
      fulvestrant (n = 1). Ten patients (58.8%) had clinical benefit (CB) (complete
      response/partial response/stable disease >= 6 months) with a median duration of
      Clinical Benefit (DoCB) of 10+ (7-27) months. Two patients remain on "withdrawal
      therapy" at the time of analysis. CONCLUSION: "Withdrawal therapy" appears to
      produce sustained CB in a significant proportion of patients. This applies not
      only to "withdrawal" from tamoxifen, but also from other categories of endocrine
      agents. "Withdrawal" from endocrine therapy is, therefore, a viable intercalating
      option between endocrine agents to minimise resistance and provide additional
      line of therapy. It should be considered as part of the sequencing of endocrine
      therapy.

PMID- 21906313
TI  - Serum leptin levels in relation to circulating cytokines, chemokines, adhesion
      molecules and angiogenic factors in normal pregnancy and preeclampsia.
AB  - OBJECTIVE: In this study, we determined circulating levels of C-reactive protein,
      several cytokines, chemokines, adhesion molecules and angiogenic factors along
      with those of leptin in healthy non-pregnant and pregnant women and preeclamptic
      patients, and investigated whether serum leptin levels were related to the
      clinical characteristics and measured laboratory parameters of the study
      participants. METHODS: Sixty preeclamptic patients, 60 healthy pregnant women and
      59 healthy non-pregnant women were involved in this case-control study. Levels of
      leptin and transforming growth factor (TGF)-beta1 in maternal sera were assessed
      by ELISA. Serum levels of interleukin (IL)-1beta, IL-1 receptor antagonist (IL
      1ra), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p40, IL-12p70, IL-18, interferon (IFN)
      gamma, tumor necrosis factor (TNF)-alpha, interferon-gamma-inducible protein (IP)
      10, monocyte chemotactic protein (MCP)-1, intercellular adhesion molecule (ICAM)
      1 and vascular cell adhesion molecule (VCAM)-1 were determined by multiplex
      suspension array. Serum C-reactive protein (CRP) concentrations were measured by
      an autoanalyzer. Serum total soluble fms-like tyrosine kinase-1 (sFlt-1) and
      biologically active placental growth factor (PlGF) levels were determined by
      electrochemiluminescence immunoassay. For statistical analyses, non-parametric
      methods were applied. RESULTS: There were significant differences in most of the
      measured laboratory parameters among the three study groups except for serum IL
      1beta and TGF-beta1 levels. Serum leptin levels were significantly higher in
      preeclamptic patients and healthy pregnant women than in healthy non-pregnant
      women. Additionally, preeclamptic patients had significantly higher leptin levels
      as compared to healthy pregnant women. Serum leptin levels were independently
      associated with BMI in healthy non-pregnant women. In healthy pregnant women,
      both BMI and serum CRP concentrations showed significant positive linear
      association with leptin levels. There were significant positive correlations
      between serum leptin concentrations of healthy pregnant women and systolic blood
      pressure, as well as serum levels of IP-10, while their serum leptin levels
      correlated inversely with fetal birth weight. In preeclamptic patients, a
      significant positive correlation was observed between serum concentrations of
      leptin and IP-10. Furthermore, elevated serum leptin level and sFlt-1/PlGF ratio
      had an additive (joint) effect in the risk of preeclampsia, as shown by the
      substantially higher odds ratios of their combination than of either alone.
      CONCLUSIONS: Simultaneous measurement of leptin with several inflammatory
      molecules and angiogenic factors in this study enabled us to investigate their
      relationship, which can help to understand the role of circulating leptin in
      normal pregnancy and preeclampsia.

PMID- 21906314
TI  - Salivary secretory immunoglobulin A secretion increases after 4-weeks ingestion
      of chlorella-derived multicomponent supplement in humans: a randomized cross over
      study.
AB  - BACKGROUND: Chlorella, a unicellular green alga that grows in fresh water,
      contains high levels of proteins, vitamins, minerals, and dietary fibers. Some
      studies have reported favorable immune function-related effects on biological
      secretions such as blood and breast milk in humans who have ingested a chlorella
      derived multicomponent supplement. However, the effects of chlorella-derived
      supplement on mucosal immune functions remain unclear. The purpose of this study
      was to investigate whether chlorella ingestion increases the salivary secretory
      immunoglobulin A (SIgA) secretion in humans using a blind, randomized, crossover
      study design. METHODS: Fifteen men took 30 placebo and 30 chlorella tablets per
      day for 4 weeks separated by a 12-week washout period. Before and after each
      trial, saliva samples were collected from a sterile cotton ball that was chewed
      after overnight fasting. Salivary SIgA concentrations were measured using ELISA.
      RESULTS: Compliance rates for placebo and chlorella ingestions were 97.0 +/- 1.0%
      and 95.3 +/- 1.6%, respectively. No difference was observed in salivary SIgA
      concentrations before and after placebo ingestion (P = 0.38). However, salivary
      SIgA concentrations were significantly elevated after chlorella ingestion
      compared to baseline (P < 0.01). No trial * period interaction was identified for
      the saliva flow rates. Although the SIgA secretion rate was not affected by
      placebo ingestion (P = 0.36), it significantly increased after 4-week chlorella
      ingestion than before intake (P < 0.01). CONCLUSIONS: These results suggest 4
      week ingestion of a chlorella-derived multicomponent supplement increases
      salivary SIgA secretion and possibly improves mucosal immune function in humans.

PMID- 21906315
TI  - Upstream molecular signaling pathways of p27(Kip1) expression in human breast
      cancer cells in vitro: differential effects of 4-hydroxytamoxifen and deficiency
      of either D-(+)-glucose or L-leucine.
AB  - BACKGROUND: The objective of this study was to investigate whether the levels of
      glucose or certain amino acids could regulate the expression of a cell cycle
      repressor protein p27(Kip1), thereby dictating the risk of cancer in either
      obesity or caloric/dietary restriction. Previously, we identified and reported
      four different upstream molecular signaling pathways of p27 expression in human
      breast cancer cells. We called these four pathways as pathway #1, #2, #3 and #4.
      We found that 4-hydroxytamoxifen - but not tamoxifen - up-regulated the
      expression of p27 using pathway #1 which consisted mainly of receptor tyrosine
      kinases and mTORC1. We now investigate, using 4-hydroxytamoxifen as a reference
      anti-cancer agents, whether (a) the moderate increase in the concentration of D
      (+)-glucose could down-regulate and, conversely, (b) the deficiency of D-(+)
      glucose or certain L-amino acids could up-regulate the expression of p27 in these
      cells using pathway #2 which consists mainly of AMPK and mTORC1. RESULTS: Using
      human MDA-MB-231 breast cancer cells in vitro, these hypotheses were tested
      experimentally by performing p27-luciferase reporter transfection assays and
      western immunoblot analyses. The results obtained are consistent with these
      hypotheses. Furthermore, the results indicated that, although 4-hydroxytamoxifen
      used primarily pathway #1 to down-regulate the phosphorylation of 4E-BP1 and up
      regulate the expression of p27, it also secondarily down-regulated the
      phosphorylation of S6K1. In contrast, the deficiency of D-(+)-glucose or L
      leucine used primarily pathway #2 to down-regulate the phosphorylation of S6K1,
      but they also secondarily down-regulated the phosphorylation of 4E-BP1 and up
      regulated the expression of p27. Finally, deficiency of D-(+)-glucose or L
      leucine - but not 4-hydroxytamoxifen - up-regulated the expression of
      mitochondrial ATP5A and SIRT3. CONCLUSIONS: (a) 4-Hydroxitamoxifen used primarily
      pathway #1 to up-regulate the expression of p27. (b) Moderate increase in the
      concentration of D-(+)-glucose used primarily pathway #2 to down-regulate the
      expression of p27. (c) Deficiency of D-(+)-glucose or L-leucine also used
      primarily pathway #2 to up-regulate the expression of p27. (d) Deficiency of D
      (+)-glucose or L-leucine - but not 4-hydroxytamoxifen - up-regulated the
      expression of mitochondrial ATP5A in the Complex V of respiratory oxidation
      phosphorylation chain and mitochondrial SIRT3. The SIRT3 is one of the seven
      mammalian anti-aging as well as anti-metabolic sirtuins.

PMID- 21906316
TI  - A preliminary investigation assessing the viability of classifying hand postures
      in seniors.
AB  - BACKGROUND: Fear of frailty is a main concern for seniors. Surface
      electromyography (sEMG) controlled assistive devices for the upper extremities
      could potentially be used to augment seniors' force while training their muscles
      and reduce their fear of frailty. In fact, these devices could both improve self
      confidence and facilitate independent leaving in domestic environments. The
      successful implementation of sEMG controlled devices for the elderly strongly
      relies on the capability of properly determining seniors' actions from their sEMG
      signals. In this research we investigated the viability of classifying hand
      postures in seniors from sEMG signals of their forearm muscles. METHODS: Nineteen
      volunteers, including seniors (70 years old in average) and young people (27
      years old in average), participated in this study and sEMG signals from four of
      their forearm muscles (i.e. Extensor Digitorum, Palmaris Longus, Flexor Carpi
      Ulnaris and Extensor Carpi Radialis) were recorded. The feature vectors were
      built by extracting features from each channel of sEMG including autoregressive
      (AR) model coefficients, waveform length and root mean square (RMS). Multi-class
      support vector machines (SVM) was used as a classifier to distinguish between
      fifteen different essential hand gestures including finger pinching. RESULTS:
      Classification of hand gestures both in the pronation and supination positions of
      the arm was possible. Classified hand gestures were: rest, ulnar deviation,
      radial deviation, grasp and four different finger pinching configurations. The
      obtained average classification accuracy was 90.6% for the seniors and 97.6% for
      the young volunteers. CONCLUSIONS: The obtained results proved that the pattern
      recognition of sEMG signals in seniors is feasible for both pronation and
      supination positions of the arm and the use of only four EMG channel is
      sufficient. The outcome of this study therefore validates the hypothesis that,
      although there are significant neurological and physical changes occurring in
      humans while ageing, sEMG controlled hand assistive devices could potentially be
      used by the older people.

PMID- 21906317
TI  - New approach for T-wave end detection on electrocardiogram: performance in noisy
      conditions.
AB  - BACKGROUND: The detection of T-wave end points on electrocardiogram (ECG) is a
      basic procedure for ECG processing and analysis. Several methods have been
      proposed and tested, featuring high accuracy and percentages of correct
      detection. Nevertheless, their performance in noisy conditions remains an open
      problem. METHODS: A new approach and algorithm for T-wave end location based on
      the computation of Trapezium's areas is proposed and validated (in terms of
      accuracy and repeatability), using signals from the Physionet QT Database. The
      performance of the proposed algorithm in noisy conditions has been tested and
      compared with one of the most used approaches for estimating the T-wave end
      point: the method based on the threshold on the first derivative. RESULTS: The
      results indicated that the proposed approach based on Trapezium's areas
      outperformed the baseline method with respect to accuracy and repeatability.
      Also, the proposed method is more robust to wideband noise. CONCLUSIONS: The
      trapezium-based approach has a good performance in noisy conditions and does not
      rely on any empirical threshold. It is very adequate for use in scenarios where
      the levels of broadband noise are significant.

PMID- 21906318
TI  - Robust spectral analysis of videocapsule images acquired from celiac disease
      patients.
AB  - BACKGROUND: Dominant frequency (DF) analysis of videocapsule endoscopy images is
      a new method to detect small intestinal periodicities that may result from
      mechanical rhythms such as peristalsis. Longer periodicity is related to greater
      image texture at areas of villous atrophy in celiac disease. However, extraneous
      features and spatiotemporal phase shift may mask DF rhythms. METHOD: The
      robustness of Fourier and ensemble averaging spectral analysis to compute DF was
      tested. Videocapsule images from the distal duodenum of 11 celiac patients (frame
      rate 2/s and pixel resolution 576 * 576) were analyzed. For patients 1, 2, ...
      11, respectively, a total of 10, 11, ..., 20 sequential images were extracted
      from a randomly selected time epoch. Each image sequence was artificially
      repeated to 200 frames, simulating periodicities of 0.2, 0.18, ..., 0.1Hz,
      respectively. Random white noise at four different levels, spatiotemporal phase
      shift, and frames with air bubbles were added. Power spectra were constructed
      pixel-wise over 200 frames, and an average spectrum was computed from the 576 *
      576 individual spectra. The largest spectral peak in the average spectrum was the
      estimated DF. Error was defined as the absolute difference between actual DF and
      estimated DF. RESULTS: For Fourier analysis, the mean absolute error between
      estimated and actual DF was 0.032 +/- 0.052Hz. Error increased with greater
      degree of random noise imposed. In contrast, all ensemble average estimates
      precisely predicted the simulated DF. CONCLUSIONS: The ensemble average DF
      estimate of videocapsule images with simulated periodicity is robust to noise and
      spatiotemporal phase shift as compared with Fourier analysis. Accurate estimation
      of DF eliminates the need to impose complex masking, extraction, and/or
      corrective preprocessing measures.

PMID- 21906319
TI  - Monitoring specific antibody responses against the hydrophilic domain of the 23
      kDa membrane protein of Schistosoma japonicum for early detection of infection in
      sentinel mice.
AB  - BACKGROUND: Schistosomiasis remains an important public health problem throughout
      tropical and subtropical countries. Humans are infected through contact with
      water contaminated with schistosome cercariae. Therefore, issuing early warnings
      on the risk of infection is an important preventive measure against
      schistosomiasis. Sentinel mice are used to monitor water body infestations, and
      identifying appropriate antibody responses to schistosome antigens for early
      detection of infection would help to improve the efficiency of this system. In
      this study we explored the potential of detecting antibodies to the hydrophilic
      domain (HD) of the 23-kDa membrane protein (Sj23HD) and soluble egg antigen (SEA)
      of Schistosome japonicum for early detection of schistosome infection in sentinel
      mice. RESULTS: Development of IgM and IgG antibody levels against Sj23HD and SEA
      in S. japonicum infected mice was evaluated over the course of 42 days post
      infection by enzyme-linked immunosorbent assay (ELISA) and immunoblotting. The
      Sj23HD and SEA specific IgM and IgG levels in mice all increased gradually over
      the course of infection, but IgM and IgG antibodies against Sj23HD presented
      earlier than those against SEA. Furthermore, the rates of positive antibody
      responses against Sj23HD were higher than those against SEA in the early stage of
      schistosome infection, suggesting that the likelihood of detecting early
      infection using anti-Sj23HD responses would be higher than that with anti-SEA
      responses. The use of immunoblotting could further improve the early detection of
      schistosome infection due to its greater sensitivity and specificity compared to
      ELISA. Additionally, the levels of Sj23HD and SEA specific antibodies positively
      correlated with the load of cercariae challenge and the duration of schistosome
      infection. CONCLUSIONS: This study demonstrated that antibody responses to the
      Sj23HD antigen could be monitored for early detection of schistosome infection in
      mice, especially by immunoblotting which demonstrated greater sensitivity and
      specificity than ELISA for detection Sj23HD antibodies.

PMID- 21906320
TI  - Impact of repeated percutaneous coronary intervention on long-term survival after
      subsequent coronary artery bypass surgery.
AB  - BACKGROUND: In the current stent era, aggressive repeated percutaneous coronary
      intervention (PCI) has become more common. The aim of this study was to
      investigate the impact of previous repeated PCI on the subsequent coronary artery
      bypass grafting (CABG). METHODS: Between January 1990 and January 2008, a total
      of 894 patients underwent first-time isolated elective CABG. Among the 894
      patients, 515 patients had had no PCI (group A), 179 patients had had single PCI
      (Group B), and 200 patients had had multiple PCI (2-15 times, mean 3.6 +/- 2.3
      times) (group C) before CABG. These groups were compared in terms of early and
      late clinical results. RESULTS: Preoperative left ventricular ejection fraction
      was significantly higher in group A (group A;58 +/- 13%, group B;54 +/- 12%, and
      group C;54 +/- 12%). Number of bypass grafts was significantly smaller in group C
      (A:3.3 +/- 1.0, B 3.4 +/- 0.9, C 3.1 +/- 1.0). Although there was no
      statistically significant difference among the groups, in-hospital mortality in
      group C was higher than that in group A and B (A:1.6%, B:1.1%, C:3.5%, p = 0.16).
      Survival analysis by Kaplan-Meier method (mean follow-up: 58 +/- 43 methods)
      revealed that freedom from all-cause death and cardiac death was significantly
      lower in group C in comparison with group A. Freedom from cardiac event was
      significantly higher in group C than that in group A. Multivariate analysis
      identified a number of previous PCI as an independent risk factor for cardiac
      death. CONCLUSIONS: Repeated PCI increased risk for long-term prognosis of
      subsequent CABG.

PMID- 21906322
TI  - Hemodynamic parameters to guide fluid therapy.
AB  - The clinical determination of the intravascular volume can be extremely
      difficult in critically ill and injured patients as well as those undergoing
      major surgery. This is problematic because fluid loading is considered the first
      step in the resuscitation of hemodynamically unstable patients. Yet, multiple
      studies have demonstrated that only approximately 50% of hemodynamically unstable
      patients in the intensive care unit and operating room respond to a fluid
      challenge. Whereas under-resuscitation results in inadequate organ perfusion,
      accumulating data suggest that over-resuscitation increases the morbidity and
      mortality of critically ill patients. Cardiac filling pressures, including the
      central venous pressure and pulmonary artery occlusion pressure, have been
      traditionally used to guide fluid management. However, studies performed during
      the past 30 years have demonstrated that cardiac filling pressures are unable to
      predict fluid responsiveness. During the past decade, a number of dynamic tests
      of volume responsiveness have been reported. These tests dynamically monitor the
      change in stroke volume after a maneuver that increases or decreases venous
      return (preload) and challenges the patients' Frank-Starling curve. These dynamic
      tests use the change in stroke volume during mechanical ventilation or after a
      passive leg raising maneuver to assess fluid responsiveness. The stroke volume is
      measured continuously and in real-time by minimally invasive or noninvasive
      technologies, including Doppler methods, pulse contour analysis, and
      bioreactance.

PMID- 21906321
TI  - A global view of porcine transcriptome in three tissues from a full-sib pair with
      extreme phenotypes in growth and fat deposition by paired-end RNA sequencing.
AB  - BACKGROUND: Elucidation of the pig transcriptome is essential for interpreting
      functional elements of the genome and understanding the genetic architecture of
      complex traits such as fat deposition, metabolism and growth. RESULTS: Here we
      used massive parallel high-throughput RNA sequencing to generate a high
      resolution map of the porcine mRNA and miRNA transcriptome in liver, longissimus
      dorsi and abdominal fat from two full-sib F2 hybrid pigs with segregated
      phenotypes on growth, blood physiological and biochemical parameters, and fat
      deposition. We obtained 8,508,418-10,219,332 uniquely mapped reads that covered
      78.0% of the current annotated transcripts and identified 48,045-122,931 novel
      transcript fragments, which constituted 17,085-29,499 novel transcriptional
      active regions in six tested samples. We found that about 18.8% of the annotated
      genes showed alternative splicing patterns, and alternative 3' splicing is the
      most common type of alternative splicing events in pigs. Cross-tissue comparison
      revealed that many transcriptional events are tissue-differential and related to
      important biological functions in their corresponding tissues. We also detected a
      total of 164 potential novel miRNAs, most of which were tissue-specifically
      identified. Integrated analysis of genome-wide association study and differential
      gene expression revealed interesting candidate genes for complex traits, such as
      IGF2, CYP1A1, CKM and CES1 for heart weight, hemoglobin, pork pH value and serum
      cholesterol, respectively. CONCLUSIONS: This study provides a global view of the
      complexity of the pig transcriptome, and gives an extensive new knowledge about
      alternative splicing, gene boundaries and miRNAs in pigs. Integrated analysis of
      genome wide association study and differential gene expression allows us to find
      important candidate genes for porcine complex traits.

PMID- 21906323
TI  - An integrated approach for prescribing fewer chest x-rays in the ICU.
AB  - Chest x-rays (CXRs) are the main imaging tool in intensive care units (ICUs).
      CXRs also are associated with concerns inherent to their use, considering both
      healthcare organization and patient perspectives. In recent years, several
      studies have focussed on the feasibility of lowering the number of bedside CXRs
      performed in the ICU. Such a decrease may result from two independent and
      complementary processes: a raw reduction of CXRs due to the elimination of
      unnecessary investigations, and replacement of the CXR by an alternative
      technique. The goal of this review is to outline emblematic examples
      corresponding to these two processes. The first part of the review concerns the
      accumulation of evidence-based data for abandoning daily routine CXRs in
      mechanically ventilated patients and adopting an on-demand prescription strategy.
      The second part of the review addresses the use of alternative techniques to
      CXRs. This part begins with the presentation of ultrasonography or capnography
      combined with epigastric auscultation for ensuring the correct position of
      enteral feeding tubes. Ultrasonography is then also presented as an alternative
      to CXR for diagnosing and monitoring pneumothoraces, as well as a valuable post
      procedural technique after central venous catheter insertion. The combination of
      the emblematic examples presented in this review supports an integrated global
      approach for decreasing the number of CXRs ordered in the ICU.

PMID- 21906325
TI  - Erythropoietin (EPO) in acute kidney injury.
AB  - Erythropoietin (EPO) is a 30.4 kDa glycoprotein produced by the kidney, and is
      mostly well-known for its physiological function in regulating red blood cell
      production in the bone marrow. Accumulating evidence, however, suggests that EPO
      has additional organ protective effects, which may be useful in the prevention or
      treatment of acute kidney injury. These protective mechanisms are multifactorial
      in nature and include inhibition of apoptotic cell death, stimulation of cellular
      regeneration, inhibition of deleterious pathways, and promotion of recovery.In
      this article, we review the physiology of EPO, assess previous work that supports
      the role of EPO as a general tissue protective agent, and explain the mechanisms
      by which it may achieve this tissue protective effect. We then focus on
      experimental and clinical data that suggest that EPO has a kidney protective
      effect.

PMID- 21906324
TI  - Perioperative fluid and volume management: physiological basis, tools and
      strategies.
AB  - Fluid and volume therapy is an important cornerstone of treating critically ill
      patients in the intensive care unit and in the operating room. New findings
      concerning the vascular barrier, its physiological functions, and its role
      regarding vascular leakage have lead to a new view of fluid and volume
      administration. Avoiding hypervolemia, as well as hypovolemia, plays a pivotal
      role when treating patients both perioperatively and in the intensive care unit.
      The various studies comparing restrictive vs. liberal fluid and volume management
      are not directly comparable, do not differ (in most instances) between colloid
      and crystalloid administration, and mostly do not refer to the vascular barrier's
      physiologic basis. In addition, very few studies have analyzed the use of
      advanced hemodynamic monitoring for volume management.This article summarizes the
      current literature on the relevant physiology of the endothelial surface layer,
      discusses fluid shifting, reviews available research on fluid management
      strategies and the commonly used fluids, and identifies suitable variables for
      hemodynamic monitoring and their goal-directed use.

PMID- 21906326
TI  - Identification and characterization of alkaline serine protease from goat skin
      surface metagenome.
AB  - Metagenomic DNA isolated from goat skin surface was used to construct plasmid
      DNA library in Escherichia coli DH10B. Recombinant clones were screened for
      functional protease activity on skim milk agar plates. Upon screening 70,000
      clones, a clone carrying recombinant plasmid pSP1 exhibited protease activity. In
      vitro transposon mutagenesis and sequencing of the insert DNA in this clone
      revealed an ORF of 1890 bp encoding a protein with 630 amino acids which showed
      significant sequence homology to the peptidase S8 and S53 subtilisin kexin
      sedolisin of Shewanella sp. This ORF was cloned in pET30b and expressed in E.
      coli BL21 (DE3). Although the cloned Alkaline Serine protease (AS-protease) was
      overexpressed, it was inactive as a result of forming inclusion bodies. After
      solubilisation, the protease was purified using Ni-NTA chromatography and then
      refolded properly to retain protease activity. The purified AS-protease with a
      molecular mass of ~63 kDa required a divalent cation (Co2+ or Mn2+) for its
      improved activity. The pH and temperature optima for this protease were 10.5 and
      42 degrees C respectively.

PMID- 21906327
TI  - Characterization of diverse natural variants of CYP102A1 found within a species
      of Bacillus megaterium.
AB  - An extreme diversity of substrates and catalytic reactions of cytochrome P450
      (P450) enzymes is considered to be the consequence of evolutionary adaptation
      driven by different metabolic or environmental demands. Here we report the
      presence of numerous natural variants of P450 BM3 (CYP102A1) within a species of
      Bacillus megaterium. Extensive amino acid substitutions (up to 5% of the total
      1049 amino acid residues) were identified from the variants. Phylogenetic
      analyses suggest that this P450 gene evolve more rapidly than the rRNA gene
      locus. It was found that key catalytic residues in the substrate channel and
      active site are retained. Although there were no apparent variations in
      hydroxylation activity towards myristic acid (C14) and palmitic acid (C16), the
      hydroxylation rates of lauric acid (C12) by the variants varied in the range of
      >25-fold. Interestingly, catalytic activities of the variants are promiscuous
      towards non-natural substrates including human P450 substrates. It can be
      suggested that CYP102A1 variants can acquire new catalytic activities through
      site-specific mutations distal to the active site.

PMID- 21906328
TI  - Alliinase from Ensifer adhaerens and Its Use for Generation of Fungicidal
      Activity.
AB  - A bacterium Ensifer adhaerens FERM P-19486 with the ability of alliinase
      production was isolated from a soil sample. The enzyme was purified for
      characterization of its general properties and evaluation of its application in
      on-site production of allicin-dependent fungicidal activity. The bacterial
      alliinase was purified 300-fold from a cell-free extract, giving rise to a
      homogenous protein band on polyacrylamide gel electrophoresis. The bacterial
      alliinase (96 kDa) consisted of two identical subunits (48 kDa), and was most
      active at 60 degrees C and at pH 8.0. The enzyme stoichiometrically converted (-)
      alliin ((-)-S-allyl-L-cysteine sulfoxide) to form allicin, pyruvic acid, and
      ammonia more selectively than (+)-alliin, a naturally occurring substrate for
      plant alliinase ever known. The C-S lyase activity was also detected with this
      bacterial enzyme when S-alkyl-L-cysteine was used as a substrate, though such a
      lyase activity is absolutely absent in alliinase of plant origin. The enzyme
      generated a fungicidal activity against Saccharomyces cerevisiae in a time- and a
      dose-dependent fashion using alliin as a stable precursor. Alliinase of Ensifer
      adhaerens FERM P-19486 is the enzyme with a novel type of substrate specificity,
      and thus considered to be beneficial when used in combination with garlic enzyme
      with respect to absolute conversion of (+/-)-alliin to allicin.

PMID- 21906329
TI  - A mutated xylose reductase increases bioethanol production more than a
      glucose/xylose facilitator in simultaneous fermentation and co-fermentation of
      wheat straw.
AB  - Genetically engineered Saccharomyces cerevisiae strains are able to ferment
      xylose present in lignocellulosic biomass. However, better xylose fermenting
      strains are required to reach complete xylose uptake in simultaneous
      saccharification and co-fermentation (SSCF) of lignocellulosic hydrolyzates. In
      the current study, haploid Saccharomyces cerevisiae strains expressing a
      heterologous xylose pathway including either the native xylose reductase (XR)
      from P. stipitis, a mutated variant of XR (mXR) with altered co-factor
      preference, a glucose/xylose facilitator (Gxf1) from Candida intermedia or both
      mXR and Gxf1 were assessed in SSCF of acid-pretreated non-detoxified wheat straw.
      The xylose conversion in SSCF was doubled with the S. cerevisiae strain
      expressing mXR compared to the isogenic strain expressing the native XR,
      converting 76% and 38%, respectively. The xylitol yield was less than half using
      mXR in comparison with the native variant. As a result of this, the ethanol yield
      increased from 0.33 to 0.39 g g-1 when the native XR was replaced by mXR. In
      contrast, the expression of Gxf1 only slightly increased the xylose uptake, and
      did not increase the ethanol production. The results suggest that ethanolic
      xylose fermentation under SSCF conditions is controlled primarily by the XR
      activity and to a much lesser extent by xylose transport.

PMID- 21906330
TI  - Advances in utilization of renewable substrates for biosurfactant production.
AB  - Biosurfactants are amphiphilic molecules that have both hydrophilic and
      hydrophobic moieties which partition preferentially at the interfaces such as
      liquid/liquid, gas/liquid or solid/liquid interfaces. Such characteristics enable
      emulsifying, foaming, detergency and dispersing properties. Their low toxicity
      and environmental friendly nature and the wide range of potential industrial
      applications in bioremediation, health care, oil and food processing industries
      makes them a highly sought after group of chemical compounds. Interest in them
      has also been encouraged because of the potential advantages they offer over
      their synthetic counterparts in many fields spanning environmental, food,
      biomedical, petrochemical and other industrial applications. Their large scale
      production and application however are currently restricted by the high cost of
      production and by the limited understanding of their interactions with cells and
      with the abiotic environment. In this paper, we review the current knowledge and
      latest advances in the search for cost effective renewable agro industrial
      alternative substrates for their production.

PMID- 21906332
TI  - Corticosteroids for severe sepsis: an evidence-based guide for physicians.
AB  - Septic shock is characterized by uncontrolled systemic inflammation that
      contributes to the progression of organ failures and eventually death. There is
      now ample evidence that the inability of the host to mount an appropriate
      hypothalamic-pituitary and adrenal axis response plays a major in overwhelming
      systemic inflammation during infections. Proinflammatory mediators released in
      the inflamed sites oppose to the anti-inflammatory response, an effect that may
      be reversed by exogenous corticosteroids. With sepsis, via nongenomic and genomic
      effects, corticosteroids restore cardiovascular homeostasis, terminate systemic
      and tissue inflammation, restore organ function, and prevent death. These effects
      of corticosteroids have been consistently found in animal studies and in most
      recent frequentist and Bayesian meta-analyses. Corticosteroids should be
      initiated only in patients with sepsis who require 0.5 MUg/kg per minute or more
      of norepinephrine and should be continued for 5 to 7 days except in patients with
      poor hemodynamic response after 2 days of corticosteroids and with a cortisol
      increment of more than 250 nmol/L after a standard adrenocorticotropin hormone
      (ACTH) test. Hydrocortisone should be given at a daily dose of 200 mg and
      preferably combined to enteral fludrocortisone at a dose of 50 MUg. Blood glucose
      levels should be kept below 150 mg/dL.

PMID- 21906331
TI  - Intensive care of the cancer patient: recent achievements and remaining
      challenges.
AB  - A few decades have passed since intensive care unit (ICU) beds have been
      available for critically ill patients with cancer. Although the initial reports
      showed dismal prognosis, recent data suggest that an increased number of patients
      with solid and hematological malignancies benefit from intensive care support,
      with dramatically decreased mortality rates. Advances in the management of the
      underlying malignancies and support of organ dysfunctions have led to survival
      gains in patients with life-threatening complications from the malignancy itself,
      as well as infectious and toxic adverse effects related to the oncological
      treatments. In this review, we will appraise the prognostic factors and discuss
      the overall perspective related to the management of critically ill patients with
      cancer. The prognostic significance of certain factors has changed over time. For
      example, neutropenia or autologous bone marrow transplantation (BMT) have less
      adverse prognostic implications than two decades ago. Similarly, because
      hematologists and oncologists select patients for ICU admission based on the
      characteristics of the malignancy, the underlying malignancy rarely influences
      short-term survival after ICU admission. Since the recent data do not clearly
      support the benefit of ICU support to unselected critically ill allogeneic BMT
      recipients, more outcome research is needed in this subgroup. Because of the
      overall increased survival that has been reported in critically ill patients with
      cancer, we outline an easy-to-use and evidence-based ICU admission triage
      criteria that may help avoid depriving life support to patients with cancer who
      can benefit. Lastly, we propose a research agenda to address unanswered
      questions.

PMID- 21906334
TI  - Septic cardiomyopathy.
AB  - Depression of left ventricular (LV) intrinsic contractility is constant in
      patients with septic shock. Because most parameters of cardiac function are
      strongly dependent on afterload, especially in this context, the cardiac
      performance evaluated at the bedside reflects intrinsic contractility, but also
      the degree of vasoplegia. Recent advances in echocardiography have allowed better
      characterization of septic cardiomyopathy. It is always reversible providing the
      patient's recovery. Unlike classic cardiomyopathy, it is not associated with high
      filling pressures, for two reasons: improvement in LV compliance and associated
      right ventricular dysfunction. Although, it is unclear to which extent it affects
      prognosis, a hyperkinetic state is indicative of a profound and persistent
      vasoplegia associated with a high mortality rate. Preliminary data suggest that
      the hemodynamic response to a dobutamine challenge has a prognostic value, but
      large studies are required to establish whether inotropic drugs should be used to
      treat this septic cardiac dysfunction.

PMID- 21906333
TI  - Efficacy and safety of recruitment maneuvers in acute respiratory distress
      syndrome.
AB  - Recruitment maneuvers (RM) consist of a ventilatory strategy that increases the
      transpulmonary pressure transiently to reopen the recruitable lung units in acute
      respiratory distress syndrome (ARDS). The rationales to use RM in ARDS are that
      there is a massive loss of aerated lung and that once the end-inspiratory
      pressure surpasses the regional critical opening pressure of the lung units,
      those units are likely to reopen. There are different methods to perform RM when
      using the conventional ICU ventilator. The three RM methods that are mostly used
      and investigated are sighs, sustained inflation, and extended sigh. There is no
      standardization of any of the above RM. Meta-analysis recommended not to use RM
      in routine in stable ARDS patients but to run them in case of life-threatening
      hypoxemia. There are some concerns regarding the safety of RM in terms of
      hemodynamics preservation and lung injury as well. The rapid rising in pressure
      can be a factor that explains the potential harmful effects of the RM. In this
      review, we describe the balance between the beneficial effects and the harmful
      consequences of RM. Recent animal studies are discussed.

PMID- 21906335
TI  - Protecting vulnerable research subjects in critical care trials: enhancing the
      informed consent process and recommendations for safeguards.
AB  - Although critically ill patients represent a vulnerable group of individuals,
      guidelines in research ethics assert that ethically acceptable research may
      proceed with such vulnerable subjects if additional safeguards are in place to
      minimize the risk of harm and exploitation. Such safeguards include the proper
      obtainment of informed consent that avoids the presence of the therapeutic
      misconception and the assessment of decisional capacity in critically ill
      patients recruited for research. Also discussed in this review are additional
      safeguards for such vulnerable subjects, as well as the issues involved with
      proxy consent. Heightened awareness to principles of ethics and provision of
      additional safeguards to enhance protections of vulnerable subjects would help to
      maintain the public trust in the research endeavor.

PMID- 21906336
TI  - Management of neurological complications of infective endocarditis in ICU
      patients.
AB  - Patients with infective endocarditis (IE) are generally referred to the
      intensive care unit (ICU) for one or more organ dysfunctions caused by
      complications of IE. Neurologic events are frequent causes of ICU admission in
      patients with IE. They can arise through various mechanisms consisting of stroke
      or transient ischemic attack, cerebral hemorrhage, mycotic aneurysm, meningitis,
      cerebral abscess, or encephalopathy. Most complications occur early during the
      course of IE and are a hallmark of left-sided abnormalities of native or
      prosthetic valves. Occlusion of cerebral arteries, with stroke or transient
      ischemic attack, accounts for 40% to 50% of the central nervous system
      complications of IE. CT scan is the most easily feasible neuroimaging in
      critically unstable patients. However, magnetic resonance imaging is more
      sensitive and when performed should follow a standardized protocol. In patients
      with ischemic stroke who are already receiving oral anticoagulant therapy, this
      treatment should be replaced by unfractionated heparin for at least 2 weeks with
      a close monitoring of coagulation tests. Mounting evidence shows that, for both
      complicated left-sided native valve endocarditis and Staphylococcus aureus
      prosthetic valve endocarditis, valve replacement combined with medical therapy is
      associated with a better outcome than medical treatment alone. In a recent
      series, approximately 50% of patients underwent valve replacement during the
      acute phase of IE before completion of antibiotic treatment. After a neurological
      event, most patients have at least one indication for cardiac surgery. Recent
      data from literature suggest that after a stroke, surgery indicated for heart
      failure, uncontrolled infection, abscess, or persisting high emboli risk should
      not be delayed, provided that the patient is not comatose or has no severe
      deficit. Neurologic complications of IE contribute to a severe prognosis in ICU
      patients. However, patients with only silent or transient stroke had a better
      prognosis than patients with symptomatic events. In addition, more than
      neurologic event per se, a better predictor of mortality is neurologic
      dysfunction, which is associated with location and extension of brain damage.
      Patients with severe neurological impairment and those with brain hemorrhage have
      the worse outcome.

PMID- 21906337
TI  - Physiological modeling, tight glycemic control, and the ICU clinician: what are
      models and how can they affect practice?
AB  - Critically ill patients are highly variable in their response to care and
      treatment. This variability and the search for improved outcomes have led to a
      significant increase in the use of protocolized care to reduce variability in
      care. However, protocolized care does not address the variability of outcome due
      to inter- and intra-patient variability, both in physiological state, and the
      response to disease and treatment. This lack of patient-specificity defines the
      opportunity for patient-specific approaches to diagnosis, care, and patient
      management, which are complementary to, and fit within, protocolized
      approaches.Computational models of human physiology offer the potential, with
      clinical data, to create patient-specific models that capture a patient's
      physiological status. Such models can provide new insights into patient condition
      by turning a series of sometimes confusing clinical data into a clear
      physiological picture. More directly, they can track patient-specific conditions
      and thus provide new means of diagnosis and opportunities for optimising
      therapy.This article presents the concept of model-based therapeutics, the use of
      computational models in clinical medicine and critical care in specific, as well
      as its potential clinical advantages, in a format designed for the clinical
      perspective. The review is presented in terms of a series of questions and
      answers. These aspects directly address questions concerning what makes a model,
      how it is made patient-specific, what it can be used for, its limitations and,
      importantly, what constitutes sufficient validation.To provide a concrete
      foundation, the concepts are presented broadly, but the details are given in
      terms of a specific case example. Specifically, tight glycemic control (TGC) is
      an area where inter- and intra-patient variability can dominate the quality of
      care control and care received from any given protocol. The overall review
      clearly shows the concept and significant clinical potential of using
      computational models in critical care medicine.

PMID- 21906338
TI  - Enhanced incorporation of 3-hydroxy-4-methylvalerate unit into biosynthetic
      polyhydroxyalkanoate using leucine as a precursor.
AB  - Ralstonia eutropha PHB-4 expressing Pseudomonas sp. 61-3 polyhydroxyalkanoate
      (PHA) synthase 1 (PhaC1Ps) synthesizes PHA copolymer containing 3-hydroxybutyrate
      (3HB) and a small amount (0.5 mol%) of 3-hydroxy-4-methylvalerate (3H4MV) from
      fructose as a carbon source. In this study, enhanced incorporation of 3H4MV into
      PHA was investigated using branched amino acid leucine as a precursor of 3H4MV.
      Leucine has the same carbon backbone as 3H4MV and is expected to be a natural and
      self-producible precursor. We found that the incorporation of 3H4MV was enhanced
      by the supplementation of excess amount (10 g/L) of leucine in the culture
      medium. This finding indicates that 3H4MV can be derived from leucine. To
      increase metabolic flux to leucine biosynthesis in the host strain by eliminating
      the feedback inhibition, the cells were subjected to N-methyl-N'-nitro-N
      nitrosoguanidine (NTG) mutagenesis and leucine analog resistant mutants were
      generated. The mutants showed statistically higher 3H4MV fraction than the parent
      strain without supplementing leucine. Additionally, by supplying excess amount of
      leucine, the mutants synthesized 3HB-based PHA copolymer containing 3.1 mol%
      3H4MV and 1.2 mol% 3-hydroxyvalerate (3HV) as minor constituents, which
      significantly affected the thermal properties of the copolymer. This study
      demonstrates that it is possible to enhance the monomer supply of 3H4MV into PHA
      by manipulating leucine metabolism.

PMID- 21906339
TI  - Breeding of a new wastewater treatment yeast by genetic engineering.
AB  - We previously developed a host vector system for the wastewater treatment yeast
      Hansenula fabianii J640. The promoter and terminator regions of the gene encoding
      glucoamylase from H. fabianii J640 were used for a new expression vector, pHFGE
      1. The performance of pHFGE-1 was compared with that of the widely used pG-1
      transformant vector. H. fabianii J640 (HF-TAMY) cells were transformed with pHFGE
      1, and Saccharomyces cerevisiae YPH-499 (SC-TAMY) cells were transformed with pG
      1, both of which carried the Taka-amylase. Expression of Taka-amylase by HF-TAMY
      showed higher than that by SC-TAMY. By using this new system, we bred the new
      wastewater treatment yeast that shows alpha-amylase activity. This yeast appears
      to grow well under experimental wastewater conditions, and is effective in
      treating model wastewater containing soluble and insoluble starch.

PMID- 21906340
TI  - Purification and characterization of hydroquinone dioxygenase from Sphingomonas
      sp. strain TTNP3.
AB  - Hydroquinone-1,2-dioxygenase, an enzyme involved in the degradation of
      alkylphenols in Sphingomonas sp. strain TTNP3 was purified to apparent
      homogeneity. The extradiol dioxygenase catalyzed the ring fission of hydroquinone
      to 4-hydroxymuconic semialdehyde and the degradation of chlorinated and several
      alkylated hydroquinones. The activity of 1 mg of the purified enzyme with
      unsubstituted hydroquinone was 6.1 MUmol per minute, the apparent Km 2.2 MUM. ICP
      MS analysis revealed an iron content of 1.4 moles per mole enzyme. The enzyme
      lost activity upon exposure to oxygen, but could be reactivated by Fe(II) in
      presence of ascorbate. SDS-PAGE analysis of the purified enzyme yielded two bands
      of an apparent size of 38 kDa and 19 kDa, respectively. Data from MALDI-TOF
      analyses of peptides of the respective bands matched with the deduced amino acid
      sequences of two neighboring open reading frames found in genomic DNA of
      Sphingomonas sp strain TTNP3. The deduced amino acid sequences showed 62% and 47%
      identity to the large and small subunit of hydroquinone dioxygenase from
      Pseudomonas fluorescens strain ACB, respectively. This heterotetrameric enzyme is
      the first of its kind found in a strain of the genus Sphingomonas sensu latu.

PMID- 21906341
TI  - Understanding urine output in critically ill patients.
AB  - Urine output often is used as a marker of acute kidney injury but also to guide
      fluid resuscitation in critically ill patients. Although decrease of urine output
      may be associated to a decrease of glomerular filtration rate due to decrease of
      renal blood flow or renal perfusion pressure, neurohormonal factors and
      functional changes may influence diuresis and natriuresis in critically ill
      patients. The purpose of this review is to discuss the mechanisms of diuresis
      regulation, which may help to interpret the urine output in critically ill
      patients and the appropriate treatment to be initiated in case of changes in
      urine output.

PMID- 21906342
TI  - Fluid management in acute lung injury and ards.
AB  - ARDS is particularly characterized by pulmonary edema caused by an increase in
      pulmonary capillary permeability. It is considered that limiting pulmonary edema
      or accelerating its resorption through the modulation of fluid intake or oncotic
      pressure could be beneficial. This review discusses the principal clinical
      studies that have made it possible to progress in the optimization of the fluid
      state during ARDS. Notably, a randomized, multicenter study has suggested that
      fluid management with the goal to obtain zero fluid balance in ARDS patients
      without shock or renal failure significantly increases the number of days without
      mechanical ventilation. On the other hand, it is accepted that patients with
      hemodynamic failure must undergo early and adapted vascular filling. Liberal and
      conservative filling strategies are therefore complementary and should ideally
      follow each other in time in the same patient whose hemodynamic state
      progressively stabilizes. At present, although albumin treatment has been
      suggested to improve oxygenation transiently in ARDS patients, no sufficient
      evidence justifies its use to mitigate pulmonary edema and reduce respiratory
      morbidity. Finally, the resorption of alveolar edema occurs through an active
      mechanism, which can be pharmacologically upregluated. In this sense, the use of
      beta-2 agonists may be beneficial but further studies are needed to confirm
      preliminary promising results.

PMID- 21906343
TI  - Biosurfactant-mediated biodegradation of straight and methyl-branched alkanes by
      Pseudomonas aeruginosa ATCC 55925.
AB  - Accidental oil spills and waste disposal are important sources for environmental
      pollution. We investigated the biodegradation of alkanes by Pseudomonas
      aeruginosa ATCC 55925 in relation to a rhamnolipid surfactant produced by the
      same bacterial strain. Results showed that the linear C11-C21 compounds in a
      heating oil sample degraded from 6% to 100%, whereas the iso-alkanes tended to be
      recalcitrant unless they were exposed to the biosurfactant; under such condition
      total biodegradation was achieved. Only the biodegradation of the commercial C12
      C19 alkanes could be demonstrated, ranging from 23% to 100%, depending on the
      experimental conditions. Pristane (a C19 branched alkane) only biodegraded when
      present alone with the biosurfactant and when included in an artificial mixture
      even without the biosurfactant. In all cases the biosurfactant significantly
      enhanced biodegradation. The electron scanning microscopy showed that cells
      depicted several adaptations to growth on hydrocarbons, such as biopolymeric
      spheres with embedded cells distributed over different layers on the spherical
      surfaces and cells linked to each other by extracellular appendages. Electron
      transmission microscopy revealed transparent inclusions, which were associated
      with hydrocarbon based-culture cells. These patterns of hydrocarbon
      biodegradation and cell adaptations depended on the substrate bioavailability,
      type and length of hydrocarbon.

PMID- 21906345
TI  - Renal and neurological side effects of colistin in critically ill patients.
AB  - Colistin is a complex polypeptide antibiotic composed mainly of colistin A and
      B. It was abandoned from clinical use in the 1970s because of significant renal
      and, to a lesser extent, neurological toxicity. Actually, colistin is
      increasingly put forward as salvage or even first-line treatment for severe
      multidrug-resistant, Gram-negative bacterial infections, particularly in the
      intensive care setting. We reviewed the most recent literature on colistin
      treatment, focusing on efficacy and toxicity issues. The method used for
      literature search was based on a PubMed retrieval using very precise
      criteria.Despite large variations in dose and duration, colistin treatment
      produces relatively high clinical cure rates. Colistin is potentially nephrotoxic
      but currently used criteria tend to overestimate the incidence of kidney injury.
      Nephrotoxicity independently predicts fewer cures of infection and increased
      mortality. Total cumulative colistin dose is associated with kidney damage,
      suggesting that shortening of treatment duration could decrease the incidence of
      nephrotoxicity. Factors that may enhance colistin nephrotoxicity (i.e., shock,
      hypoalbuminemia, concomitant use of potentially nephrotoxic drugs) must be
      combated or controlled. Neurotoxicity does not seem to be a major issue during
      colistin treatment. A better knowledge of colistin pharmacokinetics in critically
      ill patients is imperative for obtaining colistin dosing regimens that ensure
      maximal antibacterial activity at minimal toxicity.

PMID- 21906346
TI  - Noninvasive positive pressure ventilation for acute respiratory failure in
      children: a concise review.
AB  - Noninvasive positive pressure ventilation (NPPV) refers to the delivery of
      mechanical respiratory support without the use of endotracheal intubation (ETI).
      The present review focused on the effectiveness of NPPV in children > 1 month of
      age with acute respiratory failure (ARF) due to different conditions. ARF is the
      most common cause of cardiac arrest in children. Therefore, prompt recognition
      and treatment of pediatric patients with pending respiratory failure can be
      lifesaving. Mechanical respiratory support is a critical intervention in many
      cases of ARF. In recent years, NPPV has been proposed as a valuable alternative
      to invasive mechanical ventilation (IMV) in this acute setting. Recent
      physiological studies have demonstrated beneficial effects of NPPV in children
      with ARF. Several pediatric clinical studies, the majority of which were
      noncontrolled or case series and of small size, have suggested the effectiveness
      of NPPV in the treatment of ARF due to acute airway (upper or lower) obstruction
      or certain primary parenchymal lung disease, and in specific circumstances, such
      as postoperative or postextubation ARF, immunocompromised patients with ARF, or
      as a means to facilitate extubation. NPPV was well tolerated with rare major
      complications and was associated with improved gas exchange, decreased work of
      breathing, and ETI avoidance in 22-100% of patients. High FiO2 needs or high
      PaCO2 level on admission or within the first hours after starting NPPV appeared
      to be the best independent predictive factors for the NPPV failure in children
      with ARF. However, many important issues, such as the identification of the
      patient, the right time for NPPV application, and the appropriate setting, are
      still lacking. Further randomized, controlled trials that address these issues in
      children with ARF are recommended.

PMID- 21906344
TI  - Pharmacological treatment of delayed cerebral ischemia and vasospasm in
      subarachnoid hemorrhage.
AB  - Subarachnoid hemorrhage after the rupture of a cerebral aneurysm is the cause of
      6% to 8% of all cerebrovascular accidents involving 10 of 100,000 people each
      year. Despite effective treatment of the aneurysm, delayed cerebral ischemia
      (DCI) is observed in 30% of patients, with a peak on the tenth day, resulting in
      significant infirmity and mortality. Cerebral vasospasm occurs in more than half
      of all patients and is recognized as the main cause of delayed cerebral ischemia
      after subarachnoid hemorrhage. Its treatment comprises hemodynamic management and
      endovascular procedures. To date, the only drug shown to be efficacious on both
      the incidence of vasospasm and poor outcome is nimodipine. Given its modest
      effects, new pharmacological treatments are being developed to prevent and treat
      DCI. We review the different drugs currently being tested.

PMID- 21906347
TI  - Development of butanol-tolerant Bacillus subtilis strain GRSW2-B1 as a potential
      bioproduction host.
AB  - As alternative microbial hosts for butanol production with organic-solvent
      tolerant trait are in high demands, a butanol-tolerant bacterium, Bacillus
      subtilis GRSW2-B1, was thus isolated. Its tolerance covered a range of organic
      solvents at high concentration (5%v/v), with remarkable tolerance in particular
      to butanol and alcohol groups. It was susceptible for butanol acclimatization,
      which resulted in significant tolerance improvement. It has versatility for
      application in a variety of fermentation process because it has superior
      tolerance when cells were exposed to butanol either as high-density, late
      exponential grown cells (up to 5%v/v) or under growing conditions (up to
      2.25%v/v). Genetic transformation procedure was optimized, yielding the highest
      efficiency at 5.17 * 103 colony forming unit (MUg DNA)-1. Gene expression could
      be effectively driven by several promoters with different levels, where as the
      highest expression was observed with a xylose promoter. The constructed vector
      was stably maintained in the transformants, in the presence or absence of butanol
      stress. Adverse effect of efflux-mediated tetracycline resistance determinant
      (TetL) to bacterial organic-solvent tolerance property was unexpectedly observed
      and thus discussed. Overall results indicate that B. subtilis GRSW2-B1 has
      potential to be engineered and further established as a genetic host for
      bioproduction of butanol.

PMID- 21906348
TI  - Surviving sepsis: going beyond the guidelines.
AB  - The Surviving Sepsis Campaign is a global effort to improve the care of patients
      with severe sepsis and septic shock. The first Surviving Sepsis Campaign
      Guidelines were published in 2004 with an updated version published in 2008.
      These guidelines have been endorsed by many professional organizations throughout
      the world and come regarded as the standard of care for the management of
      patients with severe sepsis. Unfortunately, most of the recommendations of these
      guidelines are not evidence-based. Furthermore, the major components of the 6
      hour bundle are based on a single-center study whose validity has been recently
      under increasing scrutiny. This paper reviews the validity of the Surviving
      Sepsis Campaign 6-hour bundle and provides a more evidence-based approach to the
      initial resuscitation of patients with severe sepsis.

PMID- 21906349
TI  - Plasma proteomic profile of sulfur mustard exposed lung diseases patients using 2
      dimensional gel electrophoresis.
AB  - INTRODUCTION: Sulfur mustard "bis (2-chlroethyl) sulphide" (SM) is a chemical
      warfare agent that remains a threat to human health. The aim of this study was to
      identify protein expression signature or biomarkers that reflect chronic lung
      damages induced by SM exposure. METHODS: Prior to analysis, plasma was
      fractionated using ethanol precipitation. Using two dimensional SDS-PAGE;
      fractionated protein profiles of 20 healthy and 20 exposed patients with lung
      diseases were established. Selected protein spots were successfully identified
      with MALDI TOF MS/MS. RESULTS: The results show that alpha1 haptoglobin isoforms
      were detected in plasma of the all lung disease patients but none of the healthy
      controls. Amyloid A1 isoforms was also detected in plasma of the lung disease
      patients but none of the healthy controls. Moreover, low molecular weight
      proteins were enriched in ethanol supernatant compared to ethanol precipitate.
      CONCLUSION: Our present results and previous studies suggest that ongoing tissue
      remodeling is involved in SM exposed lung damage patients. These finding might
      improve patient care and suitable therapies.

PMID- 21906350
TI  - Hacking into bacterial biofilms: a new therapeutic challenge.
AB  - Microbiologists have extensively worked during the past decade on a particular
      phase of the bacterial cell cycle known as biofilm, in which single-celled
      individuals gather together to form a sedentary but dynamic community within a
      complex structure, displaying spatial and functional heterogeneity. In response
      to the perception of environmental signals by sensing systems, appropriate
      responses are triggered, leading to biofilm formation. This process involves
      various molecular systems that enable bacteria to identify appropriate surfaces
      on which to anchor themselves, to stick to those surfaces and to each other, to
      construct multicellular communities several hundreds of micrometers thick, and to
      detach from the community. The biofilm microbial community is a unique, highly
      competitive, and crowded environment facilitating microevolutionary processes and
      horizontal gene transfer between distantly related microorganisms. It is governed
      by social rules, based on the production and use of "public" goods, with actors
      and recipients. Biofilms constitute a unique shield against external aggressions,
      including drug treatment and immune reactions. Biofilm-associated infections in
      humans have therefore generated major problems for the diagnosis and treatment of
      diseases. Improvements in our understanding of biofilms have led to innovative
      research designed to interfere with this process.

PMID- 21906351
TI  - Proteomic profiling of the mesenteric lymph after hemorrhagic shock: Differential
      gel electrophoresis and mass spectrometry analysis.
AB  - Experiments show that upon traumatic injury the composition of mesenteric lymph
      changes such that it initiates an immune response that can ultimately result in
      multiple organ dysfunction syndrome (MODS). To identify candidate protein
      mediators of this process we carried out a quantitative proteomic study on
      mesenteric lymph from a well characterized rat shock model. We analyzed three
      animals using analytical 2D differential gel electrophoresis. Intra-animal
      variation for the majority of protein spots was minor. Functional clustering of
      proteins revealed changes arising from several global classes that give novel
      insight into fundamental mechanisms of MODS. Mass spectrometry based proteomic
      analysis of proteins in mesenteric lymph can effectively be used to identify
      candidate mediators and loss of protective agents in shock models.

PMID- 21906352
TI  - Production of polyhydroxyalkanoates from waste frying oil by Cupriavidus necator.
AB  - Polyhydroxyalkanoates (PHAs) are biopolymers, which can replace petrochemical
      plastics in many applications. However, these bioplastics are currently far more
      expensive than petrochemical plastics. Many researchers are investigating the use
      of inexpensive substrates derived from waste streams. Waste frying oil is
      abundant and can be used in PHA production without filtration.Cupriavidus necator
      (formerly known as Ralstonia eutropha) is a versatile organism for the production
      of PHAs. Small-scale batch fermentation studies have been set up, using different
      concentrations of pure vegetable oil, heated vegetable oil and waste frying oil.
      These oils are all rapeseed oils.It has been shown that Cupriavidus necator
      produced the homopolymer polyhydroxybutyrate (PHB) from the rapeseed oils. The
      achieved PHB concentration from waste frying oil was 1.2 g/l, which is similar to
      a concentration that can be obtained from glucose. The PHB harvest from pure oil
      and heated oil was 0.62 g/l and 0.9 g/l respectively. A feed of waste frying oil
      could thus achieve more biopolymer than pure vegetable oil. While the use of a
      waste product is beneficial from a life-cycle perspective, PHB is not the only
      product that can be made from waste oil. The collection of waste frying oil is
      becoming more widespread, making waste oil a good alternative to purified oil or
      glucose for PHB production.

PMID- 21906353
TI  - Two-dimensional difference gel electrophoresis (DIGE) analysis of sera from
      visceral leishmaniasis patients.
AB  - INTRODUCTION: Visceral leishmaniasis is a parasitic infection caused by
      Lesihmania donovani complex and transmitted by the bite of the phlebotomine sand
      fly. It is an endemic disease in many developing countries with more than 90% of
      the cases occurring in Bangladesh, India, Nepal, Sudan, Ethiopia and Brazil. The
      disease is fatal if untreated. The disease is conventionally diagnosed by
      demonstrating the intracellular parasite in bone marrow or splenic aspirates.
      This study was carried out to discover differentially expressed proteins which
      could be potential biomarkers. METHODS: Sera from six visceral leishmaniasis
      patients and six healthy controls were depleted of high abundant proteins by
      immunodepletion. The depleted sera were compared by 2-D Difference in gel
      electrophoresis (DIGE). Differentially expressed proteins were identified the by
      tandem mass spectrometry. Three of the identified proteins were further validated
      by western blotting. RESULTS: This is the first report of serum proteomics study
      using quantitative Difference in gel electrophoresis (DIGE) in visceral
      leishmaniasis. We identified alpha-1-acidglycoprotein and C1 inhibitor as up
      regulated and transthyretin, retinol binding protein and apolipoprotein A-I as
      down regulated proteins in visceral leishmaniasis sera in comparison with healthy
      controls. Western blot validation of C1 inhibitor, transthyretin and
      apolipoprotein A-I in a larger cohort (n = 29) confirmed significant difference
      in the expression levels (p < 0.05). CONCLUSIONS: In conclusion, DIGE based
      proteomic analysis showed that several proteins are differentially expressed in
      the sera of visceral leishmaniasis. The five proteins identified here have
      potential, either independently or in combination, as prognostic biomarkers.

PMID- 21906354
TI  - Exciting news from Clinical Proteomics.

PMID- 21906355
TI  - The ADAMs family of proteases: new biomarkers and therapeutic targets for cancer?
AB  - The ADAMs are transmembrane proteins implicated in proteolysis and cell
      adhesion. Forty gene members of the family have been identified, of which 21 are
      believed to be functional in humans. As proteases, their main substrates are the
      ectodomains of other transmembrane proteins. These substrates include precursor
      forms of growth factors, cytokines, growth factor receptors, cytokine receptors
      and several different types of adhesion molecules. Although altered expression of
      specific ADAMs has been implicated in different diseases, their best-documented
      role is in cancer formation and progression. ADAMs shown to play a role in cancer
      include ADAM9, ADAM10, ADAM12, ADAM15 and ADAM17. Two of the ADAMs, i.e., ADAM10
      and 17 appear to promote cancer progression by releasing HER/EGFR ligands. The
      released ligands activate HER/EGFR signalling that culminates in increased cell
      proliferation, migration and survival. Consistent with a causative role in
      cancer, several ADAMs are emerging as potential cancer biomarkers for aiding
      cancer diagnosis and predicting patient outcome. Furthermore, a number of
      selective ADAM inhibitors, especially against ADAM10 and ADAM17, have been shown
      to have anti-cancer effects. At least one of these inhibitors is now undergoing
      clinical trials in patients with breast cancer.

PMID- 21906356
TI  - Clinical significance of elevated B-type natriuretic peptide in patients with
      acute lung injury with or without right ventricular dilatation: an observational
      cohort study.
AB  - BACKGROUND: The primary objective of this study was to examine levels of B-type
      natriuretic peptide (BNP) in mechanically ventilated patients with acute lung
      injury and to test whether the level of BNP would be higher in patients with
      right ventricular dilatation and would predict mortality. METHODS: This was a
      prospective, observational cohort study of 42 patients conducted in the intensive
      care unit of a tertiary care university hospital. BNP was measured and
      transthoracic echocardiography was performed within 48 hours of the onset of
      acute lung injury. The left ventricular systolic and diastolic function, right
      ventricular systolic function, and cardiac output were assessed. BNP was compared
      in patients with and without right ventricular dilatation, as well as in
      survivors versus nonsurvivors. RESULTS: BNP was elevated in mechanically
      ventilated patients with acute lung injury (median 420 pg/ml; 25-75%
      interquartile range 156-728 pg/ml). There was no difference between patients with
      and without right ventricular dilatation (420 pg/ml, 119-858 pg/ml vs. 387 pg/ml,
      156-725 pg/ml; p = 0.96). There was no difference in BNP levels between the
      patients who died and those who survived at 30 days (420 pg/ml, 120-728 pg/ml vs.
      385 pg/ml, 159-1070 pg/ml; p = 0.71). CONCLUSIONS: In patients with acute lung
      injury the level of BNP is increased, but there is no difference in the BNP level
      between patients with and without right ventricular dilatation. Furthermore, BNP
      level is not predictive of mortality in this population.

PMID- 21906358
TI  - Challenges in implementing individualized medicine illustrated by antimetabolite
      therapy of childhood acute lymphoblastic leukemia.
AB  - Predicting the response to medical therapy and subsequently individualizing the
      treatment to increase efficacy or reduce toxicity has been a longstanding
      clinical goal. Not least within oncology, where many patients fail to be cured,
      and others are treated to or beyond the limit of acceptable toxicity, an
      individualized therapeutic approach is indicated. The mapping of the human genome
      and technological developments in DNA sequencing, gene expression profiling, and
      proteomics have raised the expectations for implementing genotype-phenotype data
      into the clinical decision process, but also multiplied the complex interaction
      of genetic and other laboratory parameters that can be used for therapy
      adjustments. Thus, with the advances in the laboratory techniques, post
      laboratory issues have become major obstacles for treatment individualization.
      Many of these challenges have been illustrated by studies involving childhood
      acute lymphoblastic leukemia (ALL), where each patient may receive up to 13
      different anticancer agents over a period of 2-3 years. The challenges include i)
      addressing important, but low-frequency outcomes, ii) difficulties in
      interpreting the impact of single drug or single gene response data that often
      vary across treatment protocols, iii) combining disease and host genomics with
      outcome variations, and iv) physicians' reluctance in implementing potentially
      useful genotype and phenotype data into clinical practice, since unjustified
      downward or upward dose adjustments could increase the of risk of relapse or life
      threatening complications. In this review we use childhood ALL therapy as a model
      and discuss these issues, and how they may be addressed.

PMID- 21906359
TI  - The strategy of antibiotic use in critically ill neutropenic patients.
AB  - Suspicion of sepsis in neutropenic patients requires immediate antimicrobial
      treatment. The initial regimen in critically ill patients should cover both Gram
      positive and Gram-negative pathogens, including Pseudomonas aeruginosa. However,
      the risk of selecting multidrug-resistant pathogens should be considered when
      using broad-spectrum antibiotics for a prolonged period of time. The choice of
      the first-line empirical drugs should take into account the underlying
      malignancy, local bacterial ecology, clinical presentation and severity of acute
      illness. This review provides an up-to-date guide that will assist physicians in
      choosing the best strategy regarding the use of antibiotics in neutropenic
      patients, with a special focus on critically ill patients, based on the above
      mentioned considerations and on the most recent international guidelines and
      literature.

PMID- 21906357
TI  - Aberrant glycosylation associated with enzymes as cancer biomarkers.
AB  - BACKGROUND: One of the new roles for enzymes in personalized medicine builds on a
      rational approach to cancer biomarker discovery using enzyme-associated aberrant
      glycosylation. A hallmark of cancer, aberrant glycosylation is associated with
      differential expressions of enzymes such as glycosyltransferase and glycosidases.
      The aberrant expressions of the enzymes in turn cause cancer cells to produce
      glycoproteins with specific cancer-associated aberrations in glycan structures.
      CONTENT: In this review we provide examples of cancer biomarker discovery using
      aberrant glycosylation in three areas. First, changes in glycosylation machinery
      such as glycosyltransferases/glycosidases could be used as cancer biomarkers.
      Second, most of the clinically useful cancer biomarkers are glycoproteins.
      Discovery of specific cancer-associated aberrations in glycan structures of these
      existing biomarkers could improve their cancer specificity, such as the discovery
      of AFP-L3, fucosylated glycoforms of AFP. Third, cancer-associated aberrations in
      glycan structures provide a compelling rationale for discovering new biomarkers
      using glycomic and glycoproteomic technologies. SUMMARY: As a hallmark of cancer,
      aberrant glycosylation allows for the rational design of biomarker discovery
      efforts. But more important, we need to translate these biomarkers from discovery
      to clinical diagnostics using good strategies, such as the lessons learned from
      translating the biomarkers discovered using proteomic technologies to OVA 1, the
      first FDA-cleared In Vitro Diagnostic Multivariate Index Assay (IVDMIA). These
      lessons, providing important guidance in current efforts in biomarker discovery
      and translation, are applicable to the discovery of aberrant glycosylation
      associated with enzymes as cancer biomarkers as well.

PMID- 21906360
TI  - Down-regulation of kallikrein-related peptidase 5 (KLK5) expression in breast
      cancer patients: a biomarker for the differential diagnosis of breast lesions.
AB  - BACKGROUND: Kallikrein-related peptidase 5 (KLK5) is a secreted trypsin-like
      protease of the KLK family, encoded by the KLK5 gene. KLK5 has been found to
      cleave various extracellular matrix components, as well as to activate several
      other KLK proteases, triggering the stimulation of tissue microenvironment
      proteolytic cascades. MATERIAL AND METHODS: KLK5 expression levels were
      quantified in 102 cancerous and benign breast tissue specimens, obtained by
      randomly chosen patients, using RT-qPCR assay. Subsequently, advanced
      biostatistics were applied in order to analyze the KLK5 expression profile in the
      two patients' cohorts and also to evaluate its clinical significance for the
      discrimination of breast tumors. RESULTS: A statistically significant (p < 0.001)
      down-regulation of the KLK5 expression levels were observed in the malignant
      specimens compared to the benign ones. Logistic regression and ROC curve analysis
      revealed the significant (p < 0.001) and the independent (p < 0.001) value of the
      KLK5 expression quantification, for the discrimination of the malignant from the
      benign mammary gland biopsies. Moreover, KLK5 expression levels correlate with
      the pre-menopausal status (p < 0.005) as well as the ER-negative staining (p =
      0.028) of women with breast cancer. CONCLUSIONS: The quantification of KLK5
      expression in breast tissue biopsies may be considered as a novel and independent
      biomarker for the differential diagnosis between malignant and benign tumors of
      the mammary gland.

PMID- 21906361
TI  - Spectral counting assessment of protein dynamic range in cerebrospinal fluid
      following depletion with plasma-designed immunoaffinity columns.
AB  - BACKGROUND: In cerebrospinal fluid (CSF), which is a rich source of biomarkers
      for neurological diseases, identification of biomarkers requires methods that
      allow reproducible detection of low abundance proteins. It is therefore crucial
      to decrease dynamic range and improve assessment of protein abundance. RESULTS:
      We applied LC-MS/MS to compare the performance of two CSF enrichment techniques
      that immunodeplete either albumin alone (IgYHSA) or 14 high-abundance proteins
      (IgY14). In order to estimate dynamic range of proteins identified, we measured
      protein abundance with APEX spectral counting method.Both immunodepletion methods
      improved the number of low-abundance proteins detected (3-fold for IgYHSA, 4-fold
      for IgY14). The 10 most abundant proteins following immunodepletion accounted for
      41% (IgY14) and 46% (IgYHSA) of CSF protein content, whereas they accounted for
      64% in non-depleted samples, thus demonstrating significant enrichment of low
      abundance proteins. Defined proteomics experiment metrics showed overall good
      reproducibility of the two immunodepletion methods and MS analysis. Moreover,
      offline peptide fractionation in IgYHSA sample allowed a 4-fold increase of
      proteins identified (520 vs. 131 without fractionation), without hindering
      reproducibility. CONCLUSIONS: The novelty of this study was to show the
      advantages and drawbacks of these methods side-to-side. Taking into account the
      improved detection and potential loss of non-target proteins following extensive
      immunodepletion, it is concluded that both depletion methods combined with
      spectral counting may be of interest before further fractionation, when searching
      for CSF biomarkers. According to the reliable identification and quantitation
      obtained with APEX algorithm, it may be considered as a cheap and quick
      alternative to study sample proteomic content.

PMID- 21906362
TI  - Advancing donor management research: design and implementation of a large,
      randomized, placebo-controlled trial.
AB  - BACKGROUND: Given the persistent shortage of organs for transplantation, new
      donor management strategies to improve both organ utilization and quality of
      procured organs are needed. Current management protocols for the care of the
      deceased donor before organ procurement are based on physiological rationale,
      experiential reasoning, and retrospective studies without rigorous testing.
      Although many factors contribute to the lack of controlled clinical trials in
      donor management, a major factor is the unique challenges posed by research in
      the brain-dead organ donor. METHODS AND RESULTS: This article describes the study
      design and the challenges faced during implementation of the Beta-agonists for
      Oxygenation in Lung Donors (BOLD) study, a randomized, placebo-controlled
      clinical trial of nebulized albuterol vs. placebo in 500 organ donors. The study
      design and implementation are described with emphasis on aspects of the study
      that are unique to research in brain-dead organ donors. CONCLUSIONS: Experience
      gained during the design and implementation of the BOLD study should be useful
      for investigators planning future clinical trials in the brain-dead donor
      population and for intensivists who are involved in the care of the brain-dead
      organ donor.

PMID- 21906363
TI  - FGF-23 and PTH levels in patients with acute kidney injury: A cross-sectional
      case series study.
AB  - BACKGROUND: Fibroblast growth factor-23 (FGF-23), a novel regulator of mineral
      metabolism, is markedly elevated in chronic kidney disease and has been
      associated with poor long-term outcomes. However, whether FGF-23 has an analogous
      role in acute kidney injury is unknown. The goal of this study was to measure FGF
      23 levels in critically ill patients with acute kidney injury to determine
      whether FGF-23 levels were elevated, as in chronic kidney disease. METHODS:
      Plasma FGF-23 and intact parathyroid hormone (PTH) levels were measured in 12
      patients with acute kidney injury and 8 control subjects. RESULTS: FGF-23 levels
      were significantly higher in acute kidney injury cases than in critically ill
      subjects without acute kidney injury, with a median FGF-23 level of 1948 RU/mL
      (interquartile range (IQR), 437-4369) in cases compared with 252 RU/mL (IQR, 65
      533) in controls (p = 0.01). No correlations were observed between FGF-23 and
      severity of acute kidney injury (defined by the Acute Kidney Injury Network
      criteria); among patients with acute kidney injury, FGF-23 levels were higher in
      nonsurvivors than survivors (median levels of 4446 RU/mL (IQR, 3455-5443) versus
      544 RU/mL (IQR, 390-1948; p = 0.02). Severe hyperparathyroidism (defined as
      intact PTH >250 mg/dL) was present in 3 of 12 (25%) of the acute kidney injury
      subjects versus none of the subjects without acute kidney injury, although this
      result did not meet statistical significance. CONCLUSIONS: We provide novel data
      that demonstrate that FGF-23 levels are elevated in acute kidney injury,
      suggesting that FGF-23 dysregulation occurs in acute kidney injury as well as
      chronic kidney disease. Further studies are needed to define the short- and long
      term clinical effects of dysregulated mineral metabolism in acute kidney injury
      patients.

PMID- 21906364
TI  - Serinol: small molecule - big impact.
AB  - The amino alcohol serinol (2-amino-1,3-propanediol) has become a common
      intermediate for several chemical processes. Since the 1940s serinol was used as
      precursor for synthesis of synthetic antibiotics (chloramphenicol). In the last
      years, new scopes of applications were discovered. Serinol is used for X-ray
      contrast agents, pharmaceuticals or for chemical sphingosine/ceramide synthesis.
      It can either be obtained by chemical processes based on 2-nitro-1,3-propanediol,
      dihydroxyacetone and ammonia, dihydroxyacetone oxime or 5-amino-1,3-dioxane, or
      biotechnological application of amino alcohol dehydrogenases (AMDH) or
      transaminases. This review provides a survey of synthesis, properties and
      applications for serinol.

PMID- 21906365
TI  - Study of enzymatic properties of phenol oxidase from nitrogen-fixing Azotobacter
      chroococcum.
AB  - Azotobacter chroococcum is a widespread free-living soil bacterium within the
      genus of Azotobacter known for assimilation of atmospheric nitrogen and
      subsequent conversion into nitrogenous compounds, which henceforth enrich the
      nitrogen content of soils. A. chroococcum SBUG 1484, isolated from composted
      earth, exhibits phenol oxidase (PO) activity when growing under nitrogen-fixing
      conditions. In the present study we provide incipient analysis of the crude PO
      activity expressed by A. chroococcum SBUG 1484 within comparative analysis to
      fungal crude PO from the white-rot fungus Pycnoporus cinnabarinus SBUG-M 1044 and
      tyrosinase (PPO) from the mushroom Agaricus bisporus in an attempt to reveal
      desirable properties for exploitation with future recombinant expression of this
      enzyme. Catalytic activity increased with pre-incubation at 35 degrees C; however
      70% of activity remained after pre-treatment at 50 degrees C. Native A.
      chroococcum crude PO exhibited not only strong preference for 2,6
      dimethoxyphenol, but also towards related methoxy-activated substrates as well as
      substituted ortho-benzenediols from over 40 substrates tested. Presence of CuSO4
      enhanced crude phenol oxidase activity up to 30%, whereas NaN3 (0.1 mM) was
      identified as the most inhibiting substance of all inhibitors tested. Lowest
      inhibition of crude PO activity occurred after 60 minutes of incubation in
      presence of 15% methanol and ethanol with 63% and 77% remaining activities
      respectively, and presence of DMSO even led to increasing oxidizing activities.
      Substrate scope and inhibitor spectrum strongly differentiated A. chroococcum PO
      activity comprised in crude extracts from those of PPO and confirmed distinct
      similarities to fungal PO.

PMID- 21906366
TI  - Recombinant expression and purification of the 2,5-diketocamphane 1,2
      monooxygenase from the camphor metabolizing Pseudomonas putida strain NCIMB
      10007.
AB  - Three different Baeyer-Villiger monooxygenases (BVMOs) were reported to be
      involved in the camphor metabolism by Pseudomonas putida NCIMB 10007. During (+)
      camphor degradation, 2,5-diketocamphane is formed serving as substrate for the
      2,5-diketocamphane 1,2-monooxygenase. This enzyme is encoded on the CAM plasmid
      and depends on the cofactors FMN and NADH and hence belongs to the group of type
      II BVMOs. We have cloned and recombinantly expressed the oxygenating subunit of
      the 2,5-diketocamphane 1,2-monooxygenase (2,5-DKCMO) in E. coli followed by His
      tag-based affinity purification. A range of compounds representing different BVMO
      substrate classes were then investigated, but only bicyclic ketones were
      converted by 2,5-DKCMO used as crude cell extract or after purification.
      Interestingly, also (-)-camphor was oxidized, but conversion was about 3-fold
      lower compared to (+)-camphor. Moreover, activity of purified 2,5-DKCMO was
      observed in the absence of an NADH-dehydrogenase subunit.

PMID- 21906367
TI  - Bicarbonate in diabetic ketoacidosis - a systematic review.
AB  - OBJECTIVE: This study was designed to examine the efficacy and risk of
      bicarbonate administration in the emergent treatment of severe acidemia in
      diabetic ketoacidosis (DKA). METHODS: PUBMED database was used to identify
      potentially relevant articles in the pediatric and adult DKA populations. DKA
      intervention studies on bicarbonate administration versus no bicarbonate in the
      emergent therapy, acid-base studies, studies on risk association with cerebral
      edema, and related case reports, were selected for review. Two reviewers
      independently conducted data extraction and assessed the citation relevance for
      inclusion. RESULTS: From 508 potentially relevant articles, 44 were included in
      the systematic review, including three adult randomized controlled trials (RCT)
      on bicarbonate administration versus no bicarbonate in DKA. We observed a marked
      heterogeneity in pH threshold, concentration, amount, and timing for bicarbonate
      administration in various studies. Two RCTs demonstrated transient improvement in
      metabolic acidosis with bicarbonate treatment within the initial 2 hours. There
      was no evidence of improved glycemic control or clinical efficacy. There was
      retrospective evidence of increased risk for cerebral edema and prolonged
      hospitalization in children who received bicarbonate, and weak evidence of
      transient paradoxical worsening of ketosis, and increased need for potassium
      supplementation. No studies involved patients with an initial pH < 6.85.
      CONCLUSIONS: The evidence to date does not justify the administration of
      bicarbonate for the emergent treatment of DKA, especially in the pediatric
      population, in view of possible clinical harm and lack of sustained benefits.

PMID- 21906368
TI  - Helium in the adult critical care setting.
AB  - Helium is a low-density inert gas whose physical properties are very different
      from those of nitrogen and oxygen. Such properties could be clinically useful in
      the adult critical care setting, especially in patients with upper to more distal
      airway obstruction requiring moderate to intermediate levels of FiO2. However,
      despite decades of utilization and reporting, it is still difficult to give any
      firm clinical recommendation in this setting. Numerous case reports are available
      in the context of upper airway obstruction of different origins, but there is a
      lack of controlled studies for this indication. One study reported a helium
      induced beneficial effect on surrogates of work of breathing after extubation in
      non-COPD patients, possibly in relation to laryngeal consequences of tracheal
      intubation. Physiological benefits of helium-oxygen breathing have been
      demonstrated in the context of acute severe asthma, but there is a lack of large
      controlled studies demonstrating an effect on pertinent clinical endpoints,
      except for a study reported only as an abstract, which mentioned a reduction in
      the intubation rate in helium-treated patients. Finally, there are a number of
      physiological studies in the context of COLD-COPD patients demonstrating a
      beneficial effect, mainly by a reduction in the resistive inspiratory work of
      breathing but also by a reduction in hyperinflation. Reduction of hypercapnia was
      mainly observed in spontaneously breathing and noninvasively ventilated helium
      treated patients but not in intubated patients during controlled ventilation,
      suggesting that the decrease in PaCO2 was mainly in relation to a diminution in
      CO2 production, related to the diminution in work of breathing and not an
      improved alveolar ventilation. Moreover, there is little evidence that helium
      oxygen could improve parameters of heterogeneity in such patients. Two RCTs were
      unable to demonstrate a reduction in the intubation rate in such setting, but
      they were likely underpowered. An adequately powered international multicentric
      study is ongoing and will help to determinate the exact place of the helium
      oxygen mixture in the future. The place of the mixture during the weaning period
      will deserve further evaluation.

PMID- 21906369
TI  - Enhancement of beta-xylosidase productivity in cellulase producing fungus
      Acremonium cellulolyticus.
AB  - Enzymatic hydrolysis is one of the most important processes in bioethanol
      production from lignocellulosic biomass. Acremonium cellulolyticus is a
      filamentous fungus with high cellulase production but productivity of
      hemicellulase, especially beta-xylosidase, is lower than other filamentous fungi.
      We identified 2.4 Kb beta-xylosidase gene in the A. cellulolyticus genome
      sequence information and it encoded 798 amino acids without introns. To enhance
      hemicellulase productivity in A. cellulolyticus, we transformed this fungus with
      the identified beta-xylosidase gene driven by the cellobiohydrolase Iota (cbh1)
      promoter, using the protoplast-polyethyleneglycol (PEG) method, and obtained a
      transformant, YKX1. Hydrolysis rate of xylooligosaccharides was more than 50-fold
      higher using culture supernatant from YKX1 than that from the parental strain, Y
      94. Total cellulase activity (measured by filter paper assay) in YKX1 was not
      affected by the cbh1 promoter used for expression of beta-xylosidase, and induced
      by cellulose. Since YKX1 can produce larger amount of beta-xylosidase without
      affecting cellulase productivity, it is considered to be beneficial for practical
      monosaccharide recoveries from lignocellulosic biomass.

PMID- 21906370
TI  - Functional proteomics can define prognosis and predict pathologic complete
      response in patients with breast cancer.
AB  - PURPOSE: To determine whether functional proteomics improves breast cancer
      classification and prognostication and can predict pathological complete response
      (pCR) in patients receiving neoadjuvant taxane and anthracycline-taxane-based
      systemic therapy (NST). METHODS: Reverse phase protein array (RPPA) using 146
      antibodies to proteins relevant to breast cancer was applied to three independent
      tumor sets. Supervised clustering to identify subgroups and prognosis in surgical
      excision specimens from a training set (n = 712) was validated on a test set (n =
      168) in two cohorts of patients with primary breast cancer. A score was
      constructed using ordinal logistic regression to quantify the probability of
      recurrence in the training set and tested in the test set. The score was then
      evaluated on 132 FNA biopsies of patients treated with NST to determine ability
      to predict pCR. RESULTS: Six breast cancer subgroups were identified by a 10
      protein biomarker panel in the 712 tumor training set. They were associated with
      different recurrence-free survival (RFS) (log-rank p = 8.8 E-10). The structure
      and ability of the six subgroups to predict RFS was confirmed in the test set
      (log-rank p = 0.0013). A prognosis score constructed using the 10 proteins in the
      training set was associated with RFS in both training and test sets (p = 3.2E-13,
      for test set). There was a significant association between the prognostic score
      and likelihood of pCR to NST in the FNA set (p = 0.0021). CONCLUSION: We
      developed a 10-protein biomarker panel that classifies breast cancer into
      prognostic groups that may have potential utility in the management of patients
      who receive anthracycline-taxane-based NST.

PMID- 21906371
TI  - Implications of various phosphoenolpyruvate-carbohydrate phosphotransferase
      system mutations on glycerol utilization and poly(3-hydroxybutyrate) accumulation
      in Ralstonia eutropha H16.
AB  - The enhanced global biodiesel production is also yielding increased quantities
      of glycerol as main coproduct. An effective application of glycerol, for example,
      as low-cost substrate for microbial growth in industrial fermentation processes
      to specific products will reduce the production costs for biodiesel. Our study
      focuses on the utilization of glycerol as a cheap carbon source during
      cultivation of the thermoplastic producing bacterium Ralstonia eutropha H16, and
      on the investigation of carbohydrate transport proteins involved herein. Seven
      open reading frames were identified in the genome of strain H16 to encode for
      putative proteins of the phosphoenolpyruvate-carbohydrate phosphotransferase
      system (PEP-PTS). Although the core components of PEP-PTS, enzyme I (ptsI) and
      histidine phosphocarrier protein (ptsH), are available in strain H16, a complete
      PTS-mediated carbohydrate transport is lacking. Growth experiments employing
      several PEP-PTS mutants indicate that the putative ptsMHI operon, comprising ptsM
      (a fructose-specific EIIA component of PTS), ptsH, and ptsI, is responsible for
      limited cell growth and reduced PHB accumulation (53%, w/w, less PHB than the
      wild type) of this strain in media containing glycerol as a sole carbon source.
      Otherwise, the deletion of gene H16_A0384 (ptsN, nitrogen regulatory EIIA
      component of PTS) seemed to largely compensate the effect of the deleted ptsMHI
      operon (49%, w/w, PHB). The involvement of the PTS homologous proteins on the
      utilization of the non-PTS sugar alcohol glycerol and its effect on cell growth
      as well as PHB and carbon metabolism of R. eutropha will be discussed.

PMID- 21906372
TI  - Glutamine supplementation.
AB  - Intravenous glutamine supplementation is standard care when parenteral nutrition
      is given for critical illness. There are data of a reduced mortality when
      glutamine supplementation is given. In addition, standard commercial products for
      parenteral nutrition do not contain any glutamine due to glutamine instability in
      aqueous solutions. For the majority of critical ill patients who are fed
      enterally, the available evidence is insufficient to recommend glutamine
      supplementation. Standard formulation of enteral nutrition contains some
      glutamine: 2-4 g/L. However, this dose is insufficient to normalize glutamine
      plasma concentration.Plasma concentration of glutamine is low in many patients
      with critical illness and a low level is an independent risk factor for
      mortality. A low plasma glutamine concentration is the best indicator of
      glutamine depletion. Data are emerging about how the endogenous production of
      glutamine is regulated. We know that skeletal muscle is the major producer of
      glutamine and that a part of the profound depletion of skeletal muscle seen in
      critical illness is a reflection of the need to produce glutamine.Glutamine is
      utilized in rapidly dividing cells in the splanchnic area. Quantitatively most
      glutamine is oxidized, but the availability of glutamine in surplus is important
      for the de novo synthesis of nucleotides and necessary for cell division and
      protein synthesis. More knowledge about the regulation of the endogenous
      production of glutamine is needed to outline better guidelines for glutamine
      supplementation in the future.

PMID- 21906373
TI  - Simultaneous polyhydroxyalkanoates and rhamnolipids production by Thermus
      thermophilus HB8.
AB  - The ability of Thermus thermophilus HB8 to produce simultaneously two
      environmentally-friendly biodegradable products, polyhydroxyalkanoates (PHAs) and
      rhamnolipids (RLs), using either sodium gluconate or glucose as sole carbon
      source, was demonstrated. The utilization of sodium gluconate resulted in higher
      levels of PHAs and RLs production than when glucose was used as sole carbon
      source. The initial phosphate concentration (as PO43-) influences both PHAs and
      RLs productions that were increased during cultivation time. PHAs accumulation
      was enhanced (> 300 mg/L) after 72 h of cultivation in an initial [PO43-] of 25
      mM, while RLs production (> 200 mg/L) was started after 35 h and continued until
      72 h of cultivation, in a phosphate-limited medium containing initially 5 mM of
      [PO43-]. In addition, the combine effect of initial [PO43-] and cultivation time
      on biomass, PHAs and RLs production was evaluated from 2D contour plots. The
      results revealed that low initial phosphate concentrations (up to 5 mM) and long
      incubation time (72 h) promoted RLs biosynthesis while higher initial phosphate
      concentrations (up to 25 mM) where favorable for biomass and PHAs production. The
      molecular composition of the produced bio-products was identified. The
      accumulated PHAs were co-polymers which mainly consisted of 3-hydroxydecanoate
      (3HD) as resulted by gas chromatography (GC) analysis. The secreted RLs were
      extracted and their total mixture contained both mono- and di- RLs identified by
      thin-layer chromatography (TLC). Moreover, the molecular composition of the
      produced RLs characterized in details by LC-MS analysis showed a plethora of
      diversity including mono-, and di-RLs, di-rhamno-monolipidic congeners differing
      in the length of the lipidic chain, which additionally were found to be saturated
      or unsaturated in some cases.

PMID- 21906374
TI  - Escherichia coli inactivation kinetics in anaerobic digestion of dairy manure
      under moderate, mesophilic and thermophilic temperatures.
AB  - Batch anaerobic digestion experiments using dairy manure as feedstocks were
      performed at moderate (25 degrees C), mesophilic (37 degrees C), and thermophilic
      (52.5 degrees C) temperatures to understand E. coli, an indicator organism for
      pathogens, inactivation in dairy manure. Incubation periods at 25, 37, and 52.5
      degrees C, were 61, 41, and 28 days respectively. Results were used to develop
      models for predicting E. coli inactivation and survival in anaerobic digestion.
      For modeling we used the decay of E. coli at each temperature to calculate the
      first-order inactivation rate coefficients, and these rates were used to
      formulate the time - temperature - E. coli survival relationships. We found the
      inactivation rate coefficient at 52.5 degrees C was 17 and 15 times larger than
      the inactivation rate coefficients at 25 and 37 degrees C, respectively. Decimal
      reduction times (D10; time to achieve one log removal) at 25, 37, and 52.5
      degrees C, were 9 -10, 7 - 8 days, and < 1 day, respectively. The Arrhenius
      correlation between inactivation rate coefficients and temperatures over the
      range 25 -52.5 degrees C was developed to understand the impacts of temperature
      on E. coli inactivation rate. Using this correlation, the time - temperature - E.
      coli survival relationships were derived. Besides E. coli inactivation, impacts
      of temperature on biogas production, methane content, pH change, ORP, and solid
      reduction were also studied. At higher temperatures, biogas production and
      methane content was greater than that at low temperatures. While at thermophilic
      temperature pH was increased, at mesophilic and moderate temperatures pH were
      reduced over the incubation period. These results can be used to understand
      pathogen inactivation during anaerobic digestion of dairy manure, and impacts of
      temperatures on performance of anaerobic digesters treating dairy manure.

PMID- 21906375
TI  - Harnessing the self-harvesting capability of benthic cyanobacteria for use in
      benthic photobioreactors.
AB  - Benthic species of algae and cyanobacteria (i.e., those that grow on surfaces),
      may provide potential advantages over planktonic species for some commercial
      scale biotechnological applications. A multitude of different designs of
      photobioreactor (PBR) are available for growing planktonic species but to date
      there has been little research on PBR for benthic algae or cyanobacteria. One
      notable advantage of some benthic cyanobacterial species is that during their
      growth cycle they become positively buoyant, detach from the growth surface and
      form floating mats. This 'self-harvesting' capability could be advantageous in
      commercial PBRs as it would greatly reduce dewatering costs. In this study we
      compared the growth rates and efficiency of 'self-harvesting' among three species
      of benthic cyanobacteria; Phormidium autumnale; Phormidium murrayi and
      Planktothrix sp.. Phormidium autumnale produced the greatest biomass and formed
      cohesive mats once detached. Using this strain and an optimised MLA media, a
      variety of geometries of benthic PBRs (bPBRs) were trialed. The geometry and
      composition of growth surface had a marked effect on cyanobacterial growth. The
      highest biomass was achieved in a bPBR comprising of a vertical polyethylene bag
      with loops of silicone tubing to provide additional growth surfaces. The
      productivity achieved in this bPBR was a similar order of magnitude as planktonic
      species, with the additional advantage that towards the end of the exponential
      phase the bulk of the biomass detached forming a dense mat at the surface of the
      medium.

PMID- 21906376
TI  - Retrospective evaluation of possible renal toxicity associated with continuous
      infusion of vancomycin in critically ill patients.
AB  - BACKGROUND: Continuous infusion of vancomycin is increasingly preferred as an
      alternative to intermittent administration in critically ill patients.
      Intermittent vancomycin treatment is associated with an increased occurrence of
      nephrotoxicity. This study was designed to determine the incidence and risk
      factors of acute kidney injury (AKI) during continuous infusion of vancomycin.
      METHODS: This was a retrospective, observational, two-center, cohort study in
      patients with microbiologically documented Gram-positive pneumonia and/or
      bacteremia and normal baseline renal function. Vancomycin dose was adjusted daily
      aiming at plateau concentrations of 15-25 MUg/mL. AKI was defined as an increase
      in serum creatinine of 0.3 mg/dL or a 1.5 to 2 times increase from baseline on at
      least 2 consecutive days after the initiation of vancomycin. Primary data
      analysis compared patients with AKI with patients who did not develop AKI. A
      binary logistic regression analysis using the forward stepwise method was used to
      assess the risk factors associated with AKI. RESULTS: A total of 129 patients
      were studied of whom 38 (29.5%) developed AKI. Patients with AKI had higher body
      weight (77.3 +/- 15 vs. 70.5 +/- 15.2 kg; p = 0.02), more diabetes (79% vs. 54%;
      p = 0.01), and a higher vasopressor need (87% vs. 59%; p = 0.002). Serum
      vancomycin levels, body weight, and SAPS 3 score were identified as variables
      contributing to AKI. The incidence of AKI increased substantially when treatment
      duration was prolonged (14.9 +/- 9.8 vs. 9.2 +/- 4.9 days; p = 0.05) and plasma
      levels exceeded 30 MUg/mL. CONCLUSIONS: AKI is frequently observed during
      continuous vancomycin infusion, particularly when conditions that cause acute
      (shock) or chronic (diabetes) renal dysfunction are present and vancomycin levels
      above target range are achieved. Although this study challenges the concept that
      continuous vancomycin infusion might alleviate the risk of nephrotoxicity in
      critically ill patients, a direct relationship between vancomycin and
      nephrotoxicity remains to be proven.

PMID- 21906377
TI  - A simple method to evaluate the number of bradyrhizobia on soybean seeds and its
      implication on inoculant quality control.
AB  - Soybean seeds are non-sterile and their bacterial population interferes with the
      enumeration of beneficial bacteria, making it difficult to assess survival under
      different conditions. Within this context, the principal aims of this work were:
      (1) to improve a selective media for the enumeration of B. japonicum recovered
      from inoculated soybean seeds; (2) to establish the most representative
      mathematical function for B. japonicum mortality on soybean seeds after
      inoculation; (3) to evaluate if environmental or physiological conditions modify
      B. japonicum mortality on soybean seeds; and (4) to create a new protocol for
      quality control of soybean inoculants. We successfully evaluated the combination
      of pentachloronitrobenzene and vancomycin added to the yeast-mannitol medium to
      inhibit most fungi and Gram-positive soybean microbiota, thus producing reliable
      counts of B. japonicum from inoculated soybean seeds. Percentages of recovery and
      survival factors were obtained and used to construct a two-phase exponential
      decay non-linear regression function. High temperature and desiccation decreased
      these parameters, while the optimization of temperature and the use of
      osmoprotective compounds with inoculants increased them. The use of this protocol
      minimized heterogeneity between experiments and may be considered more reliable
      than the simple expression of direct colony count of bacteria recovered from
      seeds.

PMID- 21906378
TI  - Analysis and application of Bacillus subtilis sortases to anchor recombinant
      proteins on the cell wall.
AB  - Bacillus subtilis codes for two putative sortases, YhcS and YwpE, and two
      surface proteins, YhcR and YfkN, harboring sorting motifs supposed to be
      recognized by the putative sortase(s). However, there is no experimental evidence
      to show a direct link between these sortases and sorting sequences. To study the
      role of these two putative sortases on displaying YhcR and YfkN on the cell wall,
      expression of yhcS and ywpE was analyzed by transcriptional fusions and by
      Northern blot. It turned out that yhcS gene is expressed at a higher level during
      the late stationary phase from both experiments, while ywpE expression is not
      confirmed in the Northern blot analysis. Next, we constructed yhcS and ywpE
      single and double knockout strains and plasmids that express one or both genes to
      restore the functions of the knockout strains. It could be shown that display of
      YhcR and YfkN on the surface depended on the presence of YhcS while YwpE seems
      not to play a major role if any as a sortase. Finally, the putative sorting motif
      together with a 123-amino-acid spacer derived from YhcR and YfkN designated
      YhcR123 and YfkN123, respectively, were fused to an alpha-amylase reporter
      enzyme. The fusion protein YhcR123-AmyQ could be displayed on the surface at high
      amounts, while YfkN123-AmyQ could be hardly detected. We conclude that the
      sortase YhcS can recognize and anchor YhcR on the cell wall. This result further
      indicates that the YhcR sorting sequence can be used to display recombinant
      proteins on the surface of B. subtilis cells.

PMID- 21906380
TI  - Microcirculatory alterations: potential mechanisms and implications for therapy.
AB  - Multiple experimental and human trials have shown that microcirculatory
      alterations are frequent in sepsis. In this review, we discuss the
      characteristics of these alterations, the various mechanisms potentially
      involved, and the implications for therapy. Sepsis-induced microvascular
      alterations are characterized by a decrease in capillary density with an
      increased number of stopped-flow and intermittent-flow capillaries, in close
      vicinity to well-perfused capillaries. Accordingly, the surface available for
      exchange is decreased but also is highly heterogeneous. Multiple mechanisms may
      contribute to these alterations, including endothelial dysfunction, impaired
      inter-cell communication, altered glycocalyx, adhesion and rolling of white blood
      cells and platelets, and altered red blood cell deformability. Given the
      heterogeneous nature of these alterations and the mechanisms potentially
      involved, classical hemodynamic interventions, such as fluids, red blood cell
      transfusions, vasopressors, and inotropic agents, have only a limited impact, and
      the microcirculatory changes often persist after resuscitation. Nevertheless,
      fluids seem to improve the microcirculation in the early phase of sepsis and
      dobutamine also can improve the microcirculation, although the magnitude of this
      effect varies considerably among patients. Finally, maintaining a sufficient
      perfusion pressure seems to positively influence the microcirculation; however,
      which mean arterial pressure levels should be targeted remains controversial.
      Some trials using vasodilating agents, especially nitroglycerin, showed promising
      initial results but they were challenged in other trials, so it is difficult to
      recommend the use of these agents in current practice. Other agents can markedly
      improve the microcirculation, including activated protein C and antithrombin,
      vitamin C, or steroids. In conclusion, microcirculatory alterations may play an
      important role in the development of sepsis-related organ dysfunction. At this
      stage, therapies to target microcirculation specifically are still being
      investigated.

PMID- 21906379
TI  - Ventilator-induced lung injury: historical perspectives and clinical
      implications.
AB  - Mechanical ventilation can produce lung physiological and morphological
      alterations termed ventilator-induced lung injury (VILI). Early experimental
      studies demonstrated that the main determinant of VILI is lung end-inspiratory
      volume. The clinical relevance of these experimental findings received resounding
      confirmation with the results of the acute respiratory distress syndrome (ARDS)
      Network study, which showed a 22% reduction in mortality in patients with the
      acute respiratory distress syndrome through a simple reduction in tidal volume.
      In contrast, the clinical relevance of low lung volume injury remains debated and
      the application of high positive end-expiratory pressure levels can contribute to
      lung overdistension and thus be deleterious. The significance of inflammatory
      alterations observed during VILI is debated and has not translated into clinical
      application. This review examines seminal experimental studies that led to our
      current understanding of VILI and contributed to the current recommendations in
      the respiratory support of ARDS patients.

PMID- 21906381
TI  - Immobilized pH gradient-driven paper-based IEF: a new method for fractionating
      complex peptide mixtures before MS analysis.
AB  - INTRODUCTION: The vast difference in the abundance of different proteins in
      biological samples limits the determination of the complete proteome of a cell
      type, requiring fractionation of proteins and peptides before MS analysis.
      METHODS: We present a method consisting of electrophoresis of complex mixtures of
      peptides using a strip of filter paper cut into 20 sections laid end to end over
      a 24-cm-long IPG strip, the pH gradient of which would drive the electrophoresis.
      Peptides absorbed onto individual paper pads after electrophoresis are
      subsequently recovered into a buffer solution, thus dividing a complex peptide
      mixture according to pI into 20 liquid fractions. This paper-based IEF method
      (PIEF) was compared side-by-side with a similar but liquid-based Offgel
      electrophoresis (OGE) by analyzing iTRAQ-labeled peptide mixtures of membrane
      proteins from four different cell types. RESULTS: PIEF outperformed OGE in
      resolving acidic peptides, whereas OGE did a better job in recovering relatively
      basic peptides. OGE and PIEF were quite comparable in their coverage, identifying
      almost equal number of distinct proteins (PIEF =1174; OGE = 1080). Interestingly,
      however, only 675 were identified by both of them, each method identifying many
      unique proteins (PIEF = 499; OGE = 415). Thus, the two methods uncovered almost
      40% more proteins compared to what is obtained by only one method. CONCLUSION:
      This initial investigation demonstrates the technical feasibility of PIEF for
      complementing OGE. PIEF uses standard IPG IEF equipment, requires no specialized
      apparatus (e.g., OGE fractionator) and may be integrated into peptide mapping
      strategies for clinical samples.

PMID- 21906382
TI  - Colistin: recent data on pharmacodynamics properties and clinical efficacy in
      critically ill patients.
AB  - Recent clinical studies performed in a large number of patients showed that
      colistin "forgotten" for several decades revived for the management of infections
      due to multidrug-resistant (MDR) Gram-negative bacteria (GNB) and had acceptable
      effectiveness and considerably less toxicity than that reported in older
      publications. Colistin is a rapidly bactericidal antimicrobial agent that
      possesses a significant postantibiotic effect against MDR Gram-negative
      pathogens, such as Pseudomonas aeruginosa, Acinetobacter baumannii, and
      Klebsiella pneumoniae. The optimal colistin dosing regimen against MDR GNB is
      still unknown in the intensive care unit (ICU) setting. A better understanding of
      the pharmacokinetic-pharmacodynamic relationship of colistin is urgently needed
      to determine the optimal dosing regimen. Although pharmacokinetic and
      pharmacodynamic data in ICU patients are scarce, recent evidence shows that the
      pharmacokinetics/pharmacodynamics of colistimethate sodium and colistin in
      critically ill patients differ from those previously found in other groups, such
      as cystic fibrosis patients. The AUC:MIC ratio has been found to be the parameter
      best associated with colistin efficacy. To maximize the AUC:MIC ratio, higher
      doses of colistimethate sodium and alterations in the dosing intervals may be
      warranted in the ICU setting. In addition, the development of colistin resistance
      has been linked to inadequate colistin dosing. This enforces the importance of
      colistin dose optimization in critically ill patients. Although higher colistin
      doses seem to be beneficial, the lack of colistin pharmacokinetic-pharmacodynamic
      data results in difficulty for the optimization of daily colistin dose. In
      conclusion, although colistin seems to be a very reliable alternative for the
      management of life-threatening nosocomial infections due to MDR GNB, it should be
      emphasized that there is a lack of guidelines regarding the ideal management of
      these infections and the appropriate colistin doses in critically ill patients
      with and without multiple organ failure.

PMID- 21906383
TI  - The challenge of admitting the very elderly to intensive care.
AB  - The aging of the population has increased the demand for healthcare resources.
      The number of patients aged 80 years and older admitted to the intensive care
      unit (ICU) increased during the past decade, as has the intensity of care for
      such patients. Yet, many physicians remain reluctant to admit the oldest, arguing
      a "squandering" of societal resources, that ICU care could be deleterious, or
      that ICU care may not actually be what the patient or family wants in this
      instance. Other ICU physicians are strong advocates for admission of a selected
      elderly population. These discrepant opinions may partly be explained by the
      current lack of validated criteria to select accurately the patients (of any age)
      who will benefit most from ICU hospitalization. This review describes the
      epidemiology of the elderly aged 80 years and older admitted in the ICU, their
      long-term outcomes, and to discuss some of the solutions to cope with the burden
      of an aging population receiving acute care hospitalization.

PMID- 21906384
TI  - Drug metabolizing enzyme activities versus genetic variances for drug of clinical
      pharmacogenomic relevance.
AB  - Enzymes are critically important in the transportation, metabolism, and
      clearance of most therapeutic drugs used in clinical practice today. Many of
      these enzymes have significant genetic polymorphisms that affect the enzyme's
      rate kinetics. Regarding drug metabolism, specific polymorphisms to the
      cytochrome (CYP) P450 enzyme family are linked to phenotypes that describe
      reaction rates as "ultra", "intermediate", and "poor," as referenced to
      "extensive" metabolizers that are assigned to wildtype individuals. Activity
      scores is an alternate designation that provides more genotype-to-phenotype
      resolution. Understanding the relative change in enzyme activities or rate of
      clearance of specific drugs relative to an individual's genotypes is an important
      component in the interpretation of pharmacogenomic data for personalized
      medicine. Currently, the most relevant drug metabolizing enzymes are CYP 2D6, CYP
      2C9, CYP 2C19, thiopurine methyltransferase (TPMT) and UDP
      glucuronosyltransferase (UGT). Each of these enzymes is reactive to a host of
      different drug substrates. Pharmacogenomic tests that are in routine clinical
      practice include CYP 2C19 for clopidogrel, TPMT for thiopurine drugs, and UDP-1A1
      for irinotecan. Other tests where there is considerable data but have not been
      widely implemented includes CYP 2C9 for warfarin, CYP 2D6 for tamoxifen and
      codeine, and CYP 2C19 for the proton pump inhibitors.

PMID- 21906385
TI  - Variability in the pediatric intensivists' threshold for withdrawal/limitation of
      life support as perceived by bedside nurses: a multicenter survey study.
AB  - BACKGROUND: We hypothesized that bedside nurses perceive significant variability
      in the pediatric intensivist thresholds for approaching a family about
      withdrawal/limitation of life-sustaining therapy. METHODS: All nurses working in
      four university-affiliated medical-surgical pediatric intensive care units
      staffed by 11, 7, 6, and 5 intensivists with 36, 18, 10, and 8 beds were sent
      three mailings of a survey asking questions about intensivist decisions for
      withdrawal/limitation of life-sustaining therapy. Responses were tabulated; chi
      square compared results among centers; a p < 0.05 after Bonferroni correction was
      significant. RESULTS: The response rate was 205 of 415 (49%); 152 of 205 (74%)
      disagreed with the statement that each of the intensivists had the same threshold
      for approaching a family to suggest withdrawal/limitation of life-sustaining
      therapy, with no significant difference between centers. Also, 110 of 205 (54%)
      and 119 of 205 (58%) disagreed with the statement that each intensivist has the
      same threshold of the patient's chance for survival or projected quality of life
      when making a decision to withdraw/limit life-sustaining therapy with no
      significant difference between centers. The threshold to suggest withdraw/limit
      life-sustaining therapy based on chance of survival or projected quality of life
      differs between intensivists by at least 10% according to 113 of 184 (61%) and
      121 of 184 (66%) nurses; the two larger centers had significantly higher
      difference among intensivists for projected quality of life. Fifty-five of 200
      (27%) disagreed with the statement that they would have equal confidence in each
      intensivist accepting a recommendation for withdrawal/limitation of life
      sustaining therapy for their own child, with no difference between centers.
      CONCLUSIONS: Bedside pediatric intensive care unit nurses in this multicenter
      Canadian study perceive wide variability in intensivist thresholds for
      approaching a family to suggest withdrawal/limitation of life-sustaining therapy.

PMID- 21906386
TI  - Sensitivity to electrical stimulation of human immunodeficiency virus type 1 and
      MAGIC-5 cells.
AB  - To determine the sensitivities to low electrical potential of human
      immunodeficiency virus type 1 (HIV-1) and its target cells, HIV-1 and MAGIC-5
      cells were directly stimulated with a constant direct current potential of 1.0 V
      (vs. Ag/AgCl). HIV-1 was incubated for 3 h at 37 degrees C on a poly-L-lysine
      coated indium-tin oxide electrode, and then stimulated by an electrical
      potential. MAGIC-5 cells were seeded onto the electrically stimulated HIV-1 and
      cultured for 3 days at 37 degrees C. HIV-1-infected cells were measured by
      multinuclear activation via a galactosidase indicator assay. MAGIC-5 cells were
      also stimulated by an electrical potential of 1.0 V; cell damage, proliferation
      and apoptosis were evaluated by trypan blue staining, cell counting and in situ
      apoptosis detection, respectively. HIV-1 was found to be damaged to a greater
      extent by electrical stimulation than the cells. In particular, after application
      of a 1.0-V potential for 3 min, HIV-1LAI and HIV-1KMT infection were inhibited by
      about 90%, but changes in cell damage, proliferation and apoptosis were virtually
      undetectable. These results suggested that HIV-1 is significantly more
      susceptible to low electrical potential than cells. This finding could form the
      basis of a novel therapeutic strategy against HIV-1 infection.

PMID- 21906387
TI  - Septic AKI in ICU patients. diagnosis, pathophysiology, and treatment type,
      dosing, and timing: a comprehensive review of recent and future developments.
AB  - Evidence is accumulating showing that septic acute kidney injury (AKI) is
      different from non-septic AKI. Specifically, a large body of research points to
      apoptotic processes underlying septic AKI. Unravelling the complex and
      intertwined apoptotic and immuno-inflammatory pathways at the cellular level will
      undoubtedly create new and exciting perspectives for the future development
      (e.g., caspase inhibition) or refinement (specific vasopressor use) of
      therapeutic strategies. Shock complicating sepsis may cause more AKI but also
      will render treatment of this condition in an hemodynamically unstable patient
      more difficult. Expert opinion, along with the aggregated results of two recent
      large randomized trials, favors continuous renal replacement therapy (CRRT) as
      preferential treatment for septic AKI (hemodynamically unstable). It is suggested
      that this approach might decrease the need for subsequent chronic dialysis. Large
      scale introduction of citrate as an anticoagulant most likely will change CRRT
      management in intensive care units (ICU), because it not only significantly
      increases filter lifespan but also better preserves filter porosity. A possible
      role of citrate in reducing mortality and morbidity, mainly in surgical ICU
      patients, remains to be proven. Also, citrate administration in the predilution
      mode appears to be safe and exempt of relevant side effects, yet still requires
      rigorous monitoring. Current consensus exists about using a CRRT dose of 25
      ml/kg/h in non-septic AKI. However, because patients should not be undertreated,
      this implies that doses as high as 30 to 35 ml/kg/h must be prescribed to account
      for eventual treatment interruptions. Awaiting results from large, ongoing
      trials, 35 ml/kg/h should remain the standard dose in septic AKI, particularly
      when shock is present. To date, exact timing of CRRT is not well defined. A
      widely accepted composite definition of timing is needed before an appropriate
      study challenging this major issue can be launched.

PMID- 21906388
TI  - Clinical detection and monitoring of acute pulmonary embolism: proof of concept
      of a computer-based method.
AB  - BACKGROUND: The diagnostic ability of computer-based methods for cardiovascular
      system (CVS) monitoring offers significant clinical potential. This research
      tests the clinical applicability of a newly improved computer-based method for
      the proof of concept case of tracking changes in important hemodynamic indices
      due to the influence acute pulmonary embolism (APE). METHODS: Hemodynamic
      measurements from a porcine model of APE were used to validate the method. Of
      these measurements, only those that are clinically available or inferable were
      used in to identify pig-specific computer models of the CVS, including the aortic
      and pulmonary artery pressure, stroke volume, heart rate, global end diastolic
      volume, and mitral and tricuspid valve closure times. Changes in the computer
      derived parameters were analyzed and compared with experimental metrics and
      clinical indices to assess the clinical applicability of the technique and its
      ability to track the disease state. RESULTS: The subject-specific computer models
      accurately captured the increase in pulmonary resistance (Rpul), the main
      cardiovascular consequence of APE, in all five pigs trials, which related well
      (R2 = 0.81) with the experimentally derived pulmonary vascular resistance. An
      increase in right ventricular contractility was identified, as expected,
      consistent with known reflex responses to APE. Furthermore, the modeled right
      ventricular expansion index (the ratio of right to left ventricular end diastolic
      volumes) closely followed the trends seen in the measured data (R2 = 0.92) used
      for validation, with sharp increases seen in the metric for the two pigs in a
      near-death state. These results show that the pig-specific models are capable of
      tracking disease-dependent changes in pulmonary resistance (afterload), right
      ventricular contractility (inotropy), and ventricular loading (preload) during
      induced APE. Continuous, accurate estimation of these fundamental metrics of
      cardiovascular status can help to assist clinicians with diagnosis, monitoring,
      and therapy-based decisions in an intensive care environment. Furthermore,
      because the method only uses measurements already available in the ICU, it can be
      implemented with no added risk to the patient and little extra cost. CONCLUSIONS:
      This computer-based monitoring method shows potential for real-time, continuous
      diagnosis and monitoring of acute CVS dysfunction in critically ill patients.

PMID- 21906389
TI  - Characteristics of Chinese patients with cough in primary care centre.
AB  - BACKGROUND: Cough is one of the most common respiratory symptoms and is well
      characterized in specialized cough clinics with high success rates of diagnosis
      and treatment. However, there is a paucity of data regarding cough in primary
      care settings. The present study aimed at investigating clinical epidemiology of
      cough through a national study of two questionnaire surveys sent to primary care
      physicians in China. METHODS: Approximately 18,000 subjects recruited were having
      daytime or night symptoms of cough and diagnoses of respiratory disease from
      February 2005 to April 2006 as Survey 1 and from June 2007 to December 2007 as
      Survey 2. Patients suffering from respiratory malignancy, hyperthyroidism,
      hypertension, heart disease, diabetes, severe hypohepatia or renal dysfunction,
      pregnancy, possible pregnancy or lactation, neutropenia were not eligible.
      Information regarding demography, history of allergies, symptomatic profile,
      treatment and curative effects for cough was elicited. RESULTS: 8216
      questionnaires were collected in Survey 1 and 9711 in Survey 2. The mean values
      of ages were 25.7 and 22.3 years old, respectively. Symptoms included
      expectoration (74% and 76%), wheeze (59% and 74%), breathlessness (22% and 26%),
      chest pain (9% and 13%) and fever (15% and 18%). About 15% and 23% patients had
      hypersusceptibility, of whom 6% to 17% had a family history. More than 50% of the
      cases had histories of allergic rhinitis, asthma, conjunctivitis or atopic
      dermatitis. Asthma, COPD, and bronchitis were dominant etiologies of cough.
      Procaterol or the combination of antibiotics and steroids were used as the
      treatment. CONCLUSION: Causes and outcomes of cough differed with ages and time
      in this particular national study, while successful and precise diagnosis and
      management of cough in primary care settings need to be further improved in
      China.

PMID- 21906390
TI  - High frequency chest wall oscillation for asthma and chronic obstructive
      pulmonary disease exacerbations: a randomized sham-controlled clinical trial.
AB  - BACKGROUND: High frequency chest wall oscillation (HFCWO) is used for airway
      mucus clearance. The objective of this study was to evaluate the use of HFCWO
      early in the treatment of adults hospitalized for acute asthma or chronic
      obstructive pulmonary disease (COPD). METHODS: Randomized, multi-center, double
      masked phase II clinical trial of active or sham treatment initiated within 24
      hours of hospital admission for acute asthma or COPD at four academic medical
      centers. Patients received active or sham treatment for 15 minutes three times a
      day for four treatments. Medical management was standardized across groups. The
      primary outcomes were patient adherence to therapy after four treatments (minutes
      used/60 minutes prescribed) and satisfaction. Secondary outcomes included change
      in Borg dyspnea score (>= 1 unit indicates a clinically significant change),
      spontaneously expectorated sputum volume, and forced expired volume in 1 second.
      RESULTS: Fifty-two participants were randomized to active (n = 25) or sham (n =
      27) treatment. Patient adherence was similarly high in both groups (91% vs. 93%;
      p = 0.70). Patient satisfaction was also similarly high in both groups. After
      four treatments, a higher proportion of patients in the active treatment group
      had a clinically significant improvement in dyspnea (70.8% vs. 42.3%, p = 0.04).
      There were no significant differences in other secondary outcomes. CONCLUSIONS:
      HFCWO is well tolerated in adults hospitalized for acute asthma or COPD and
      significantly improves dyspnea. The high levels of patient satisfaction in both
      treatment groups justify the need for sham controls when evaluating the use of
      HFCWO on patient-reported outcomes. Additional studies are needed to more fully
      evaluate the role of HFCWO in improving in-hospital and post-discharge outcomes
      in this population. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00181285.

PMID- 21906391
TI  - Effects of calcium channel blockers on glucose tolerance, inflammatory state, and
      circulating progenitor cells in non-diabetic patients with essential
      hypertension: a comparative study between azelnidipine and amlodipine on glucose
      tolerance and endothelial function--a crossover trial (AGENT).
AB  - BACKGROUND: Hypertension is associated with impaired glucose tolerance and
      insulin resistance. Medical treatment that interferes with various steps in the
      renin-angiotensin system improves glucose tolerance and insulin resistance.
      However, it remains unclear if long-acting calcium channel blockers (CCBs) such
      as azelnidipine and amlodipine affect glucose tolerance and insulin resistance in
      clinical practice. METHODS: Seventeen non-diabetic patients with essential
      hypertension who had controlled blood pressure levels using amlodipine (5 mg/day)
      were enrolled in this study. After randomization, either azelnidipine (16 mg/day)
      or amlodipine (5 mg/day) was administered in a crossover design for 12-weeks. At
      baseline and the end of each CCB therapy, samples of blood and urine were
      collected and 75 g oral glucose tolerance test (OGTT) was performed. In addition,
      hematopoietic progenitor cells (HPCs) were measured at each point by flow
      cytometry and endothelial functions were measured by fingertip pulse amplitude
      tonometry using EndoPAT. RESULTS: Although blood pressure levels were identical
      after each CCB treatment, the heart rate significantly decreased after
      azelnidipine administration than that after amlodipine administration (P <
      0.005). Compared with amlodipine administration, azelnidipine significantly
      decreased levels of glucose and insulin 120 min after the 75 g OGTT (both P <
      0.05). Serum levels of high-sensitivity C-reactive protein (P = 0.067) and
      interleukin-6 (P = 0.035) were decreased. Although endothelial functions were not
      different between the two medication groups, the number of circulating HPCs was
      significantly increased after azelnidipine administration (P = 0.016).
      CONCLUSIONS: These results suggest that azelnidipine treatment may have
      beneficial effects on glucose tolerance, insulin sensitivity, the inflammatory
      state, and number of circulating progenitor cells in non-diabetic patients with
      essential hypertension.

PMID- 21906392
TI  - Genome-wide expression assay comparison across frozen and fixed postmortem brain
      tissue samples.
AB  - BACKGROUND: Gene expression assays have been shown to yield high quality genome
      wide data from partially degraded RNA samples. However, these methods have not
      yet been applied to postmortem human brain tissue, despite their potential to
      overcome poor RNA quality and other technical limitations inherent in many
      assays. We compared cDNA-mediated annealing, selection, and ligation (DASL)- and
      in vitro transcription (IVT)-based genome-wide expression profiling assays on RNA
      samples from artificially degraded reference pools, frozen brain tissue, and
      formalin-fixed brain tissue. RESULTS: The DASL-based platform produced expression
      results of greater reliability than the IVT-based platform in artificially
      degraded reference brain RNA and RNA from frozen tissue-based samples. Although
      data associated with a small sample of formalin-fixed RNA samples were poor when
      obtained from both assays, the DASL-based platform exhibited greater reliability
      in a subset of probes and samples. CONCLUSIONS: Our results suggest that the DASL
      based gene expression-profiling platform may confer some advantages on mRNA
      assays of the brain over traditional IVT-based methods. We ultimately consider
      the implications of these results on investigations of neuropsychiatric
      disorders.

PMID- 21906393
TI  - Gut flora enhance bacterial clearance in lung through toll-like receptors 4.
AB  - BACKGROUND: The influence of the gut flora on lung inflammatory reaction against
      bacterial challenge remains undefined. This study was designed to investigate
      whether gut flora enhances lung defense against E.coli pneumonia through TLR4
      signaling. METHODS: C3H/HeN (WT) mice and C3H/HeJ (TLR4 deficient) mice were
      treated with antibiotics in drinking water for 4 weeks to deplete gut commensal
      microflora. At week 3, drinking water was supplemented with lipopolysaccharide
      (LPS); a ligand for TLR4, to trigger TLRs in intestinal tract. At the end of 4th
      week, E.coli was injected to trachea to induce E.coli pneumonia. RESULTS: We
      found that commensal depletion by antibiotic pretreatment before E.coli pneumonia
      challenge induced a 30% decrease of MPO activity in the lung, a significant
      decrease of bacterial killing activity of alveolar macrophage, and bacterial
      counts in C3H/HeN mice but not in C3H/HeJ (TLR4 deficient) mice. LPS, a TLR4
      ligand, supplementation during antibiotic pretreatment reversed these effects and
      decreased E.coli pneumonia-induced mortality in C3H/HeN mice. Furthermore,
      commensal depletion induced a suppression of NF-kappaB DNA binding activity and
      an increase of KC, MIP-2, IL-1beta expression in the lung in C3H/HeN mice but not
      in C3H/HeJ mice. CONCLUSIONS: Taken together with that commensal depletion
      increased E.coli pneumonia-induced mortality and LPS supplementation decreased
      it, we conclude that gut flora enhances bacterial clearance against E.coli
      pneumonia through TLR4.

PMID- 21906394
TI  - Serotype and genotype analysis of dengue virus by sequencing followed by
      phylogenetic analysis using samples from three mini outbreaks-2007-2009 in
      Pakistan.
AB  - BACKGROUND: Since the first reported outbreak of dengue hemorrhagic fever in
      Pakistan, several mini outbreaks have erupted in the region. Dengue virus
      serotype 3 (DEN-3) was first documented in 2005 outbreak in Karachi. Reports show
      that serotype 3 is prevalent in Lahore since 2008. Serotype 2 (DEN-2) is the
      major circulating serotype in Pakistan as it is documented since 1994. We have
      conducted a detailed study of three outbreaks of dengue virus infection that
      occurred in years 2007, 2008 and 2009 in Lahore by using molecular techniques
      such as PCR and nucleotide sequencing of the C-prM gene junction of Dengue virus.
      RESULTS: Through the analysis of 114 serum samples collected over the period of
      three years (2007-2009), total 20 patients were found to be infected with dengue
      virus. In year 2007, four were positive for serotype 2 and one sample was
      positive for serotype DEN-3. In 2008, five samples had concurrent infection with
      serotypes DEN-2 and DEN-3 while three samples were infected only with serotype
      DEN-2. In year 2009, one sample had concurrent infection with serotypes DEN-2 and
      DEN-3 while six were positive for serotype DEN-2 only. CONCLUSIONS: Our study
      showed that serotype DEN-2 was dominant in positive samples of dengue virus
      infection collected during the period of three years (2007-2009). The other
      serotype present was serotype DEN-3. Genotypes of serotype DEN-2 and serotype DEN
      3 were subtype IV and subtype III, respectively.

PMID- 21906395
TI  - Male predominance of pneumonia and hospitalization in pandemic influenza A (H1N1)
      2009 infection.
AB  - BACKGROUND: Pandemic influenza A (H1N1) disproportionately affects different age
      groups. The purpose of the current study was to describe the age and gender
      difference of pandemic influenza A (H1N1) cases that lead to pneumonia,
      hospitalization or ICU admission. METHODS: Data were collected retrospectively
      between May 2009 and December 2009. All of the diagnoses of H1N1 were confirmed
      by real-time reverse-transcription polymerase chain reaction (RT-PCR). RESULTS:
      During the study period there were 3402 cases of RT-PCR positive H1N1, among
      which 1812 were males and 1626 were adults (> 15 years of age). 6% (206/3402) of
      patients required hospitalization, 3.6% (122/3402) had infiltrates on chest
      radiographs, and 0.70% (24/3402) were admitted to intensive care unit (ICU). The
      overall fatality rate was 0.1% (4/3402). The rate of hospitalization was sharply
      increased in patients >= 50 years of age especially in male. Out of 122 pneumonia
      patients, 68.8% (84 patients) were male. Among the patients admitted to the ICU,
      70.8% (17 patients) were male. Approximately 1 of 10 H1N1-infected patients
      admitted to the ICU were >= 70 years of age. CONCLUSIONS: Among the confirmed
      cases of H1N1, the ICU admission rate was < 1% and the case fatality rate was
      0.1%. Male had a significantly higher rate of pneumonia and hospital admission.
      These findings should be taken into consideration when developing vaccination and
      treatment strategies.

PMID- 21906396
TI  - Point of care technology or standard laboratory service in an emergency
      department: is there a difference in time to action? A randomised trial.
AB  - BACKGROUND: Emergency Departments (ED) have a high flow of patients and time is
      often crucial. New technologies for laboratory analysis have been developed,
      including Point of Care Technologies (POCT), which can reduce the transport time
      and time of analysis significantly compared with central laboratory services.
      However, the question is if the time to clinical action is also reduced if a
      decisive laboratory answer is available during the first contact between the
      patient and doctor. The present study addresses this question: Does a laboratory
      answer, provided by POCT to the doctor who first attends the patient on
      admission, change the time to clinical decision in commonly occurring diseases in
      an ED compared with the traditional service from a central laboratory? METHODS:
      We performed a randomised clinical trial with parallel design and allocation
      ratio 1:1. The eligibility Criteria were: All patients referred from General
      Practitioner or another referring doctor suspected for a deep venous thrombosis
      (DVT), acute coronary syndrome (ACS), acute appendicitis (AA) or acute infection
      (ABI). The outcome measure was the time spend from the blood sample was taken to
      a clinical decision was made. RESULTS: The study period took place in October-
      November 2009 and from February to April 2010. 239 patients were eligible for the
      study. There was no difference between the groups suspected for DVT, ACS and AA,
      but a significant reduction in time for the ABI group (p:0.009), where the median
      time to decision was reduced from 7 hours and 33 minutes to 4 hours and 38
      minutes when POCT was used. Only in the confirmation of ABI the time to action
      was significantly shorter. CONCLUSIONS: Fast laboratory answers by POCT in an ED
      reduce the time to clinical decision significantly for bacterial infections. We
      suggest further studies which include a sufficient number of patients on deep
      venous thrombosis, acute appendicitis and acute coronary syndrome.

PMID- 21906397
TI  - Prolonged survival after splenectomy in Wiskott-Aldrich syndrome: a case report.
AB  - Wiskott-Aldrich syndrome is a rare X-linked immunodeficiency disorder that is
      characterized by a variable clinical phenotype. Matched donor bone marrow
      transplantation is currently the only curative therapeutic option. We present the
      case of a 24-year-old male who was diagnosed at the age of seven with Wiskott
      Aldrich syndrome. He did not respond to intravenous gammaglobulin and he
      experienced recurrent pulmonary infections despite prophylactic antibiotics. The
      patient had no matched donor. At the age of nine, he was submitted to splenectomy
      and his platelet count was normalized. Fifteen years later, the patient remains
      asymptomatic with a normal platelet count. He is still receiving prophylactic
      antibiotics and no bleeding episodes or septic complications have been reported.
      This case demonstrates that splenectomy can represent a safe therapeutic option
      in selected WAS patients, provided that there is a tight follow-up program,
      patient education and adherence to guidelines regarding post-splenectomy
      prophylaxis.

PMID- 21906398
TI  - The impact of surgical outcome after pancreaticoduodenectomy in elderly patients.
AB  - BACKGROUND: The elderly population has increased in many countries. Indications
      for cancer treatment in elderly patients have expanded, because surgical
      techniques and medical management have improved remarkably.
      Pancreaticoduodenectomy (PD) requires high-quality techniques and perioperative
      management methods. If it is possible for elderly patients to withstand an
      aggressive surgery, age should not be considered a contraindication for PD.
      Appropriate preoperative evaluation of elderly patients will lead to their safer
      management. The purpose of the present study was to evaluate the safety of PD in
      patients older than 75 years and to show the influence of advanced age on the
      morbidity and mortality associated with this operation. PATIENTS AND METHODS:
      Subjects were 98 patients who underwent PD during the time period from April 2005
      to April 2011. During this study, 31 patients were 75 years of age or older
      (group A), and the other 67 patients were less than 75 years old (group B).
      Preoperative demographic and clinical data, surgical procedure, pathologic
      diagnosis, postoperative course and complication details were collected
      prospectively and they were analyzed in two group. RESULTS: There was no
      statistical difference between patient groups in terms of gender, comorbidity,
      preoperative drainage, diagnosis, or laboratory data. Preoperative albumin values
      were lower in group A (P = 0.04). The mean surgical time in group A was 408.1 +/-
      73.47 min. Blood loss and blood transfusion were not significantly different
      between both groups. There was no statistical differences in mortality rate (P =
      0.14), morbidity rate (P = 0.43), and mean length of hospital stay (P = 0.22)
      between both groups. Long-term survival was also no statistically significant
      difference between the two groups using the log-rank test (P = 0.10). CONCLUSION:
      It cannot be ignored that the elderly population is getting larger. We must
      investigate the management of elderly patients after PD and prepare further for
      more experiences of PD. If appropriate surgical management is provided to elderly
      patients, we suggest that PD will lead to no adverse effects after surgery, and
      PD can be performed safely in elderly patients. We conclude that age should not
      be a contraindication to PD.

PMID- 21906399
TI  - Incidence of pancreatitis, secondary causes, and treatment of patients referred
      to a specialty lipid clinic with severe hypertriglyceridemia: a retrospective
      cohort study.
AB  - BACKGROUND: Severe hypertriglyceridemia (HTG) is one cause of acute pancreatitis,
      yet the level of plasma triglycerides likely to be responsible for inducing
      pancreatitis has not been clearly defined. METHODS AND RESULTS: A retrospective
      cohort study was conducted on patients presenting non-acutely to the Healthy
      Heart Program Lipid Clinic at St. Paul's Hospital with a TG level > 20 mM (1772
      mg/dl) between 1986 and 2007. Ninety-five patients with TG > 20 mM at the time of
      referral were identified, in who follow up data was available for 84. Fifteen
      patients (15.8%), with a mean outpatient TG level of 38.1 mM, had a history of
      acute pancreatitis. Among 91 additional patients with less severe HTG, none had a
      history of pancreatitis when TG were between 10 and 20 mM. Among patients with TG
      > 20 mM on presentation, 8 (8.5%), with a mean TG level of 67.8 mM, exhibited
      eruptive xanthomata. A diet high in carbohydrates and fats (79%) and obesity
      (47.6%) were the two most frequent secondary causes of HTG at initial visit. By
      2009, among patients with follow up data 53% exhibited either pre-diabetes or
      overt Type 2 diabetes mellitus. Upon referral only 23 patients (24%) were
      receiving a fibrate as either monotherapy or part of combination lipid-lowering
      therapy. Following initial assessment by a lipid specialist this rose to 84%, and
      remained at 67% at the last follow up visit. CONCLUSIONS: These results suggest
      hypertriglyceridemia is unlikely to be the primary cause of acute pancreatitis
      unless TG levels are > 20 mM, that dysglycemia, a diet high in carbohydrates and
      fats, and obesity are the main secondary causes of HTG, and that fibrates are
      frequently overlooked as the drug of first choice for severe HTG.

PMID- 21906400
TI  - Infrared thermography fails to visualize stimulation-induced meridian-like
      structures: comment by Rixin Chen and Zhimai Lv and reply from Gerhard Litscher.
AB  - A comment on G. Litscher: Infrared thermography fails to visualize stimulation
      induced meridian-like structures. Biomed. Eng. OnLine 2005, 4:38 (15 June 2005),
      with a response by the author.

PMID- 21906401
TI  - Generation and characterization of an Advillin-Cre driver mouse line.
AB  - Progress in the somatosensory field has been restricted by the limited number of
      genetic tools available to study gene function in peripheral sensory neurons.
      Here we generated a Cre-driver mouse line that expresses Cre-recombinase from the
      locus of the sensory neuron specific gene Advillin. These mice displayed almost
      exclusive Cre-mediated recombination in all peripheral sensory neurons. As such,
      the Advillin-Cre-driver line will be a powerful tool for targeting peripheral
      neurons in future investigations.

PMID- 21906402
TI  - Cognitive function is associated with risk aversion in community-based older
      persons.
AB  - BACKGROUND: Emerging data from younger and middle-aged persons suggest that
      cognitive ability is negatively associated with risk aversion, but this
      association has not been studied among older persons who are at high risk of
      experiencing loss of cognitive function. METHODS: Using data from 369 community
      dwelling older persons without dementia from the Rush Memory and Aging Project,
      an ongoing longitudinal epidemiologic study of aging, we examined the correlates
      of risk aversion and tested the hypothesis that cognition is negatively
      associated with risk aversion. Global cognition and five specific cognitive
      abilities were measured via detailed cognitive testing, and risk aversion was
      measured using standard behavioral economics questions in which participants were
      asked to choose between a certain monetary payment ($15) versus a gamble in which
      they could gain more than $15 or gain nothing; potential gamble gains ranged from
      $21.79 to $151.19 with the gain amounts varied randomly over questions. We first
      examined the bivariate associations of age, education, sex, income and cognition
      with risk aversion. Next, we examined the associations between cognition and risk
      aversion via mixed models adjusted for age, sex, education, and income. Finally,
      we conducted sensitivity analyses to ensure that our results were not driven by
      persons with preclinical cognitive impairment. RESULTS: In bivariate analyses,
      sex, education, income and global cognition were associated with risk aversion.
      However, in a mixed effect model, only sex (estimate = -1.49, standard error (SE)
      = 0.39, p < 0.001) and global cognitive function (estimate = -1.05, standard
      error (SE) = 0.34, p < 0.003) were significantly inversely associated with risk
      aversion. Thus, a lower level of global cognitive function and female sex were
      associated with greater risk aversion. Moreover, performance on four out of the
      five cognitive domains was negatively related to risk aversion (i.e., semantic
      memory, episodic memory, working memory, and perceptual speed); performance on
      visuospatial abilities was not. CONCLUSION: A lower level of cognitive ability
      and female sex are associated with greater risk aversion in advanced age.

PMID- 21906403
TI  - Decrease in Shiga toxin expression using a minimal inhibitory concentration of
      rifampicin followed by bactericidal gentamicin treatment enhances survival of
      Escherichia coli O157:H7-infected BALB/c mice.
AB  - BACKGROUND: Treatment of Escherichia coli O157:H7 infections with antimicrobial
      agents is controversial due to an association with potentially fatal sequelae.
      The production of Shiga toxins is believed to be central to the pathogenesis of
      this organism. Therefore, decreasing the expression of these toxins prior to
      bacterial eradication may provide a safer course of therapy. METHODS: The utility
      of decreasing Shiga toxin gene expression in E. coli O157:H7 with rifampicin
      prior to bacterial eradication with gentamicin was evaluated in vitro using real
      time reverse-transcription polymerase chain reaction. Toxin release from treated
      bacterial cells was assayed for with reverse passive latex agglutination. The
      effect of this treatment on the survival of E. coli O157:H7-infected BALB/c mice
      was also monitored. RESULTS: Transcription of Shiga toxin-encoding genes was
      considerably decreased as an effect of treating E. coli O157:H7 in vitro with the
      minimum inhibitory concentration (MIC) of rifampicin followed by the minimum
      bactericidal concentration (MBC) of gentamicin (> 99% decrease) compared to
      treatment with gentamicin alone (50-75% decrease). The release of Shiga toxins
      from E. coli O157:H7 incubated with the MIC of rifampicin followed by addition of
      the MBC of gentamicin was decreased as well. On the other hand, the highest
      survival rate in BALB/c mice infected with E. coli O157:H7 was observed in those
      treated with the in vivo MIC equivalent dose of rifampicin followed by the in
      vivo MBC equivalent dose of gentamicin compared to mice treated with gentamicin
      or rifampicin alone. CONCLUSIONS: The use of non-lethal expression-inhibitory
      doses of antimicrobial agents prior to bactericidal ones in treating E. coli
      O157:H7 infection is effective and may be potentially useful in human infections
      with this agent in addition to other Shiga toxin producing E. coli strains.

PMID- 21906404
TI  - Effectiveness of motivational interviewing and physical activity on prescription
      on leisure exercise time in subjects suffering from mild to moderate
      hypertension.
AB  - BACKGROUND: Physical inactivity is considered to be the strongest individual risk
      factor for poor health in Sweden. It has been shown that increased physical
      activity can reduce hypertension and the risk of developing cardiovascular
      diseases. The objective of the present pilot study was to investigate whether a
      combination of Motivational Interviewing (MI) and Physical Activity on
      Prescription (PAP) would increase leisure exercise time and subsequently improve
      health-related variables. METHODS: This pilot study was of a repeated measures
      design, with a 15 months intervention in 31 patients with mild to moderate
      hypertension. Primary outcome parameter was leisure exercise time and secondary
      outcome parameters were changes in blood pressure, Body Mass Index (BMI), waist
      circumference, lipid status, glycosylated haemoglobin (HbA1c) and maximal oxygen
      uptake (VO2 max). Assessments of the outcome parameters were made at baseline and
      after 3, 9 and 15 months. RESULTS: Leisure exercise time improved significantly
      from < 60 min/week at baseline to a mean activity level of 300 (+/- 165)
      minutes/week at 15 months follow up. Furthermore, statistically significant
      improvements (p < 0.05) were observed in systolic (-14,5 +/- 8.3 mmHg) and
      diastolic blood pressure (-5,1 +/- 5.8 mmHg), heart rate (-4.9 +/- 8.7 beats/min,
      weight (-1.2 +/- 3.4 kg) BMI -0.6 +/- 1.2 kg/m2), waist circumference (-3.5 +/-
      4.1 cm) as well as in VO2 max (2.94 +/- 3.8 ml/kg and 0.23, +/- 0.34 lit/min)
      upon intervention as compared to baseline. CONCLUSIONS: A 15 month intervention
      period with MI, in combination with PAP, significantly increased leisure exercise
      time and improved health-related variables in hypertensive patients. This outcome
      warrants further research to investigate the efficacy of MI and PAP in the
      treatment of mild to moderate hypertension.

PMID- 21906405
TI  - Impact of perinatal prebiotic consumption on gestating mice and their offspring:
      a preliminary report.
AB  - To assess the impact of prebiotic supplementation during gestation and fetal and
      early neonatal life, gestating BALB/cj dam mice were fed either a control or a
      prebiotic (galacto-oligosaccharides-inulin, 9:1 ratio)-enriched diet throughout
      pregnancy and lactation, and allowed to nurse their pups until weaning. At the
      time of weaning, male offspring mice were separated from their mothers, weaned to
      the same solid diet as their dam and their growth was monitored until killed 48 d
      after weaning. Prebiotic treatment affected neither the body-weight gain nor the
      food intake of pregnant mice. In contrast, at the time of weaning, pups that had
      been nursed by prebiotic-fed dams had a higher body weight (11.0 (se 1.2) g) than
      pups born from control dams (9.8 (se 0.9) g). At 48 d after weaning,
      significantly higher values were observed for colon length and muscle mass in the
      offspring of prebiotic-fed dams (1.2 (se 0.1) cm/cm and 5.7 (se 1.8) mg/g,
      respectively), compared with control offspring (1.1 (se 0.1) cm/cm and 2.9 (se
      0.9) mg/g, respectively), without any difference in spleen and stomach weight, or
      serum leptin concentration. The present preliminary study suggests that altering
      the fibre content of the maternal diet during both pregnancy and lactation
      enhances offspring growth, through an effect on intestinal and muscle mass rather
      than fat mass accretion.

PMID- 21906406
TI  - Regulatory responses to excess zinc ingestion in growing rats.
AB  - The growth of weaning piglets is effectively improved by feeding a high-Zn diet
      (3000 mg Zn/kg of diet). The present study examined whether feeding a diet
      supplemented with Zn (1016-3000 mg/kg) for 10 d induces growth benefits in rats.
      In addition, tissue weight, Zn content of tissues and expression of Zn
      transporters were examined in these rats. Zn supplementation did not
      significantly increase body weight. Breaking line model analyses indicated that
      the weight of the pancreas, the organ most sensitive to excess Zn, significantly
      decreased with increasing Zn intake beyond 15.2 mg/d. Excess Zn has been
      suggested to accumulate in the liver, kidney and bone in order to protect the
      pancreas. Zn concentrations in the plasma, liver, kidney and femur increased with
      increasing Zn intake up to approximately 30 mg/d, whereas those in the pancreas
      increased up to 8.4 mg/d and decreased by Zn intake beyond 8.4 mg/d. The
      expression levels of the Zn transporters Zip4 and ZnT1 in the intestinal
      epithelium were significantly lower in rats fed a diet supplemented with 1016
      mg/kg Zn compared to those fed the basal diet. The present study reveals that (1)
      excess Zn intake does not accelerate growth in rats, but is detrimental to the
      pancreas, (2) the excess Zn is effectively accumulated in the liver, kidney and
      bone, without sufficient protection of the pancreas and (3) expression of Zn
      transporters is down-regulated in response to excess Zn intake.

PMID- 21906408
TI  - The importance of reducing SFA to limit CHD.

PMID- 21906407
TI  - Dietary plasma proteins attenuate the innate immunity response in a mouse model
      of acute lung injury.
AB  - We examined whether oral plasma protein supplements affect the innate immune
      response in a model of acute lung inflammation. Mice were fed diets supplemented
      with 8 % spray-dried plasma (SDP) or 2 % plasma Ig concentrate (IC) from day 19
      (weaning) until day 34. The mice were challenged with intranasal
      lipopolysaccharide (LPS) at day 33 (and killed 24 h later for cytokine and
      leucocyte analyses) or at day 34 (and killed 6 h later for cytokine
      determinations). In bronchoalveolar lavage fluid (BALF), LPS increased the number
      of leucocytes by twenty-sevenfold, an effect that was partly prevented by both
      SDP and IC, and by twentyfold the percentage of activated monocytes, which was
      partly prevented by SDP. In the lung tissue, LPS increased the infiltrated
      leucocytes, and this effect was prevented in part by SDP. In unchallenged mice,
      both SDP and IC diets reduced the percentage of resident neutrophils and
      monocytes (P < 0.05). In the blood, both SDP and IC completely prevented LPS
      dependent monocyte activation (CD14+; P < 0.05). LPS dramatically increased the
      concentration of cytokines (TNF-alpha, IL-1alpha, IL-6, granulocyte-macrophage
      colony-stimulating factor and granulocyte colony-stimulating factor) and
      chemokines (CXCL1, CCL2, CCL3 and CCL4) in BALF. The acute response of cytokine
      production was reduced by 20-80 % by both SDP and IC. For chemokines, plasma
      supplements had no effect on LPS-induced CXCL1 expression but significantly
      reduced CCL2, CCL3 and CCL4 production (P < 0.05). The results support the view
      that dietary plasma proteins can be used to attenuate endotoxin-associated lung
      inflammation.

PMID- 21906409
TI  - The first dominant co-circulation of both dengue and chikungunya viruses during
      the post-monsoon period of 2010 in Delhi, India.
AB  - Independent outbreaks of dengue virus (DENV) infection and sporadic cases of
      chikungunya virus (CHIKV) have been recorded in the metropolitan city of Delhi on
      several occasions in the past. However, during a recent 2010 arboviral outbreak
      in Delhi many cases turned negative for DENV. This prompted us to use duplex
      reverse transcriptase-polymerase chain reaction (D-RT-PCR) to establish the
      aetiology of dengue/chikungunya through sequencing of CprM and E1 genes of dengue
      and chikungunya viruses. Interestingly, for the first time, both DENV and CHIKV
      co-circulated simultaneously and in equally dominant proportion during the post
      monsoon period of 2010. DENV-1 genotype III and the East Central South African
      genotype of CHIKV were associated with post-monsoon spread of these viruses.

PMID- 21906411
TI  - Meteorological factors and El Nino Southern Oscillation are independently
      associated with dengue infections.
AB  - Our objective was to determine the association between temperature, humidity,
      rainfall and dengue activity in Singapore, after taking into account lag periods
      as well as long-term climate variability such as the El Nino Southern Oscillation
      Index (SOI). We used a Poisson model which allowed for autocorrelation and
      overdispersion in the data. We found weekly mean temperature and mean relative
      humidity as well as SOI to be significantly and independently associated with
      dengue notifications. There was an interaction effect by periods of dengue
      outbreaks, but periods where El Nino was present did not moderate the
      relationship between humidity and temperature with dengue notifications. Our
      results help to understand the temporal trends of dengue in Singapore, and
      further reinforce the findings that meteorological factors are important in the
      epidemiology of dengue.

PMID- 21906410
TI  - The incidence of varicella and herpes zoster in Taiwan during a period of
      increasing varicella vaccine coverage, 2000-2008.
AB  - The introduction and the widespread use of the varicella vaccine in Taiwan has
      led to a 75-80% decrease in the incidence of varicella in children. However the
      vaccine's long-term impact on the incidence of herpes zoster (HZ) has attracted
      attention. By controlling gender, underlying diseases, and age effects, a Poisson
      regression was applied on the 2000-2008 chart records of 240 000 randomly
      selected residents who enrolled in the Universal National Health Insurance. The
      results show that, as the vaccine coverage in children increases, the incidence
      of varicella decreases. However, the incidence of HZ increased even before the
      implementation of the free varicella vaccination programme in 2004, particularly
      in females. The increase in the incidence of HZ cannot be entirely and directly
      attributed to the widespread vaccination of children. Continuous monitoring is
      needed to understand the secular trends in HZ before and after varicella
      vaccination in Taiwan and in other countries.

PMID- 21906412
TI  - Rapid assessment of influenza vaccine effectiveness: analysis of an internet
      based cohort.
AB  - The effectiveness of influenza vaccination programmes is seldom known during an
      epidemic. We developed an internet-based system to record influenza-like symptoms
      and response to infection in a participating cohort. Using self-reports of
      influenza-like symptoms and of influenza vaccine history and uptake, we estimated
      vaccine effectiveness (VE) without the need for individuals to seek healthcare.
      We found that vaccination with the 2010 seasonal influenza vaccine was
      significantly protective against influenza-like illness (ILI) during the 2010
      2011 influenza season (VE 52%, 95% CI 27-68). VE for individuals who received
      both the 2010 seasonal and 2009 pandemic influenza vaccines was 59% (95% CI 27
      77), slightly higher than VE for those vaccinated in 2010 alone (VE 46%, 95% CI 9
      68). Vaccinated individuals with ILI reported taking less time off work than
      unvaccinated individuals with ILI (3.4 days vs. 5.3 days, P<0.001).

PMID- 21906413
TI  - M-protein gene-type distribution and hyaluronic acid capsule in group A
      Streptococcus clinical isolates in Chile: association of emm gene markers with
      csrR alleles.
AB  - Streptococcus pyogenes causes a variety of infections because of virulence
      factors such as capsular hyaluronic acid and M protein. The aim of this study was
      to determine emm types and capsule phenotype in 110 isolates of S. pyogenes from
      patients with invasive (sterile sites) and non-invasive (mainly pharyngitis)
      infections in Chile, and the relationship between both virulence factors. The
      most abundant types found were emm12, emm1, emm4 and emm28 and their distribution
      was similar to that seen in Latin America and developed countries, but very
      different from that in Asia and Pacific Island countries. Ten of 16 emm types
      identified in pharyngeal isolates were found in sterile-site isolates, and three
      of nine emm types of sterile-site isolates occurred in pharyngeal isolates; three
      emm subtypes were novel. The amount of hyaluronic acid was significantly higher
      in sterile-site isolates but did not differ substantially among emm types. Only
      three isolates were markedly capsulate and two of them had mutations in the csrR
      gene that codes for a repressor of capsule synthesis genes. We found a non-random
      association between emm types and csrR gene alleles suggesting that horizontal
      gene transfer is not freely occurring in the population.

PMID- 21906414
TI  - Risk factors for 30-day mortality in adult patients with pneumococcal
      bacteraemia, and the impact of antimicrobial resistance on clinical outcomes.
AB  - The clinical impact of antimicrobial resistance on the outcome of pneumococcal
      bacteraemia has remained unclear. This study aimed to evaluate risk factors for
      mortality and determine the impact of antimicrobial resistance on clinical
      outcomes. A total of 150 adult patients with pneumococcal bacteraemia were
      identified over a period of 11 years at Seoul National University Hospital. Of
      the 150 patients, 122 (81.3%) had penicillin-susceptible (Pen-S) strains and 28
      (18.7%) penicillin-non-susceptible (Pen-NS) strains; 43 (28.7%) had erythromycin
      susceptible (EM-S) strains and 107 (71.3%) erythromycin-non-susceptible (EM-NS)
      strains. On multivariate analysis, elevated APACHE II score [odds ratio (OR)
      1.24, 95% confidence interval (CI) 1.14-1.34, P<0.001) and presence of solid
      organ tumour (OR 2.99, 95% CI 1.15-7.80, P=0.025) were independent risk factors
      for mortality. Neither erythromycin resistance nor penicillin resistance had a
      significant effect on clinical outcomes. However, for the 76 patients with
      pneumococcal pneumonia, the time required for defervescence was significantly
      longer in the EM-NS group than in the EM-S group (5.45 +/- 4.39 vs. 2.93 +/-
      2.56, P=0.03 by log rank test). In conclusion, antimicrobial resistance does not
      have an effect on mortality in adult patients with pneumococcal bacteraemia.

PMID- 21906415
TI  - Zoonotic bacteria, antimicrobial use and antimicrobial resistance in ornamental
      fish: a systematic review of the existing research and survey of aquaculture
      allied professionals.
AB  - Using systematic review methodology, global research reporting the frequency of
      zoonotic bacterial pathogens, antimicrobial use (AMU) and antimicrobial
      resistance (AMR) in ornamental fish, and human illness due to exposure to
      ornamental fish, was examined. A survey was performed to elicit opinions of
      aquaculture-allied personnel on the frequency of AMU and AMR in ornamental fish.
      The most commonly reported sporadic human infections were associated with
      Mycobacterium marinum, while Salmonella Paratyphi B var. Java was implicated in
      all reported outbreaks. Aeromonas spp. were most frequently investigated (n=10
      studies) in 25 studies surveying ornamental fish from various sources. High
      levels of resistance were reported to amoxicillin, penicillin, tetracycline and
      oxytetracycline, which was also in agreement with the survey respondents' views.
      Studies on AMU were not found in our review. Survey respondents reported frequent
      use of quinolones, followed by tetracyclines, nitrofurans, and aminoglycosides.
      Recommendations for future surveillance and public education efforts are
      presented.

PMID- 21906416
TI  - Effects of climatic elements on Campylobacter-contaminated chicken products in
      Japan.
AB  - Japanese weather data for areas that produced Campylobacter spp.-positive chicken
      products were compared with those for areas producing negative samples. Regarding
      samples produced during the period of rising temperature (spring and summer), the
      mean weekly air temperatures for Campylobacter-positive samples were higher than
      those for negative samples for the period of the week in which the samples were
      purchased (18.7  degrees C vs. 13.1  degrees C, P = 0.006) to a 12-week lag (12
      weeks before purchasing samples; 7.9  degrees C vs. 3.4  degrees C, P = 0.009).
      Significant differences in weekly mean minimum humidity and sunshine duration per
      day were also observed for 1- and 2-week lag periods. We postulated that the high
      air temperature, high humidity and short duration of sunshine for the chicken
      rearing period increased Campylobacter colonization in chickens during the period
      of rising temperature. Consequently, the number of Campylobacter-contaminated
      chicken products on the market in Japan may fluctuate because of the climatic
      conditions to which reared chickens are exposed.

PMID- 21906417
TI  - Seasonality--still confusing.

PMID- 21906418
TI  - Comprehensive comparison of various techniques for the analysis of elemental
      distributions in thin films.
AB  - The present work shows results on elemental distribution analyses in Cu(In,Ga)Se2
      thin films for solar cells performed by use of wavelength-dispersive and energy
      dispersive X-ray spectrometry (EDX) in a scanning electron microscope, EDX in a
      transmission electron microscope, X-ray photoelectron, angle-dependent soft X-ray
      emission, secondary ion-mass (SIMS), time-of-flight SIMS, sputtered neutral mass,
      glow-discharge optical emission and glow-discharge mass, Auger electron, and
      Rutherford backscattering spectrometry, by use of scanning Auger electron
      microscopy, Raman depth profiling, and Raman mapping, as well as by use of
      elastic recoil detection analysis, grazing-incidence X-ray and electron
      backscatter diffraction, and grazing-incidence X-ray fluorescence analysis. The
      Cu(In,Ga)Se2 thin films used for the present comparison were produced during the
      same identical deposition run and exhibit thicknesses of about 2 MUm. The
      analysis techniques were compared with respect to their spatial and depth
      resolutions, measuring speeds, availabilities, and detection limits.

PMID- 21906420
TI  - An enhancement of the firing activity of dopamine neurons as a common denominator
      of antidepressant treatments?

PMID- 21906419
TI  - Acute D-serine treatment produces antidepressant-like effects in rodents.
AB  - Research suggests that dysfunctional glutamatergic signalling may contribute to
      depression, a debilitating mood disorder affecting millions of individuals
      worldwide. Ketamine, a N-methyl-D-aspartate (NMDA) receptor antagonist, exerts
      rapid antidepressant effects in approximately 70% of patients. Glutamate evokes
      the release of D-serine from astrocytes and neurons, which then acts as a co
      agonist and binds at the glycine site on the NR1 subunit of NMDA receptors.
      Several studies have implicated glial deficits as one of the underlying facets of
      the neurobiology of depression. The present study tested the hypothesis that D
      serine modulates behaviours related to depression. The behavioural effects of a
      single, acute D-serine administration were examined in several rodent tests of
      antidepressant-like effects, including the forced swim test (FST), the female
      urine sniffing test (FUST) following serotonin depletion, and the learned
      helplessness (LH) paradigm. D-serine significantly reduced immobility in the FST
      without affecting general motor function. Both D-serine and ketamine
      significantly rescued sexual reward-seeking deficits caused by serotonin
      depletion in the FUST. Finally, D-serine reversed LH behaviour, as measured by
      escape latency, number of escapes, and percentage of mice developing LH. Mice
      lacking NR1 expression in forebrain excitatory neurons exhibited a depression
      like phenotype in the same behavioural tests, and did not respond to D-serine
      treatment. These findings suggest that D-serine produces antidepressant-like
      effects and support the notion of complex glutamatergic dysfunction in
      depression. It is unclear whether D-serine has a convergent influence on
      downstream synaptic plasticity cascades that may yield a similar therapeutic
      profile to NMDA antagonists like ketamine.

PMID- 21906422
TI  - Updating the Italian Society for Rheumatology recommendations for biologic
      therapy in adult patients with inflammatory rheumatic diseases.

PMID- 21906421
TI  - Longitudinal predictors of past-year non-suicidal self-injury and motives among
      college students.
AB  - BACKGROUND: Non-suicidal self-injury (NSSI) is the deliberate and direct injuring
      of body tissue without suicidal intent for purposes not socially sanctioned. Few
      studies have examined the correlates of NSSI among young adults. This study aimed
      to identify predictors of lifetime and past-year NSSI, and describe motives for
      NSSI and disclosure of NSSI to others. METHOD: Interviews were conducted annually
      with 1081 students enrolled in the College Life Study, a prospective longitudinal
      study conducted at a large public mid-Atlantic university. NSSI characteristics
      were assessed at Year 4. Demographic and predictor variables were assessed during
      Years 1 to 4. Multivariate logistic regression models were used to identify
      correlates of lifetime NSSI and predictors of past-year NSSI. RESULTS: The
      prevalence of past-year and lifetime NSSI was 2% and 7% respectively (>70% were
      female for both lifetime and past-year NSSI). Seven percent of NSSI cases self
      injured once, whereas almost half self-injured six or more times. Independent
      predictors of past-year NSSI were maternal depression, non-heterosexual
      orientation, affective dysregulation and depression. Independent predictors of
      lifetime NSSI were depression, non-heterosexual orientation, paternal depression
      and female sex. One in six participants with NSSI had attempted suicide by young
      adulthood. The three most commonly reported motives for NSSI were mental
      distress, coping and situational stressors. Most (89%) told someone about their
      NSSI, most commonly a friend (68%). CONCLUSIONS: This study identified unique
      predictors of NSSI, which should help to elucidate its etiology and has
      implications for early identification and interventions.

PMID- 21906423
TI  - Recommendations for the use of biologic therapy in rheumatoid arthritis: update
      from the Italian Society for Rheumatology I. Efficacy.
AB  - Given the availability of novel biologic agents for the treatment of rheumatoid
      arthritis (RA), various national scientific societies have developed specific
      recommendations in order to assist rheumatologists in prescribing these drugs.
      The Italian Society for Rheumatology (Societa Italiana di Reumatologia, SIR)
      decided to update its recommendations and, to this end, a systematic literature
      review was carried out and the evidence derived from it was discussed and
      summarised as expert opinions. Levels of evidence, strength of recommendations
      and levels of agreement were reported. The recommendations reported are intended
      to help prescribing rheumatologists to optimise the use of biologic agents in
      patients with RA seen in everyday practice; they are not to be considered as a
      regulatory rule.

PMID- 21906424
TI  - Recommendations for the use of biologic therapy in rheumatoid arthritis: update
      from the Italian Society for Rheumatology II. Safety.
AB  - Given the availability of novel biologic agents for the treatment of rheumatoid
      arthritis (RA), various national scientific societies have developed specific
      recommendations in order to assist rheumatologists in prescribing these drugs.
      The Italian Society for Rheumatology (Societa Italiana di Reumatologia, SIR)
      decided to update its recommendations, and, to this end, a systematic literature
      review was performed and the evidence derived from it was discussed and
      summarized as expert opinions. Levels of evidence and strength of recommendations
      were reported. The recommendations reported refer to the safety of biologic
      agents and are intended to help prescribing rheumatologists to optimise the use
      of biologic agents in patients with RA seen in everyday practice; they are not to
      be considered as a regulatory rule.

PMID- 21906425
TI  - Recommendations for the use of biologic therapy in the treatment of psoriatic
      arthritis: update from the Italian Society for Rheumatology.
AB  - OBJECTIVES: To update the 2006 Italian Society for Rheumatology recommendations
      for the use of biologic (TNF-alpha blocking) agents in the treatment of psoriatic
      arthritis (PsA). METHODS: A panel of experts performed a literature search and
      identified the items that required updating on the basis of new published data. A
      draft of the updated recommendations was circulated to a group of Italian
      Rheumatologists with a specific expertise in PsA and in therapy with biologic
      agents, and their suggestions were incorporated in the final version. RESULTS: A
      consensus was achieved regarding the initiation and the monitoring of anti-TNF
      alpha agents in PsA. Inclusion and exclusion criteria were defined and specific
      recommendations were made for patients with psoriatic peripheral synovitis,
      spondylitis, enthesitis, and dactylitis, respectively. We also specified criteria
      for assessment of response to treatment and for withholding and withdrawal of
      therapy. CONCLUSIONS: These recommendations may be used for guidance in deciding
      which patients with PsA should receive biologic therapy. Further updates of these
      recommendations may be published on the basis of the results of new clinical
      studies and of data from post-marketing surveillance.

PMID- 21906426
TI  - Recommendations for the use of biologic therapy from the Italian Society for
      Rheumatology: off-label use.
AB  - The advent of biological agents has provided further opportunities to treat
      resistant or relapsing rheumatic diseases, with robust data for rheumatoid
      arthritis and spondyloarthritis coming from randomised controlled trials. However
      there are data also on other rare inflammatory rheumatic diseases even if the
      evidence available may be heterogeneous and/or controversial. Another challenging
      scenario is represented by diseases that are not uncommon, but that may present
      with multiple manifestations and prove resistant to conventional therapies, thus
      requiring the use of biological agents. To assist physicians in making correct
      therapeutic choices in such cases, the Italian Society for Rheumatology (SIR) has
      developed specific recommendations for the use of biological agents in rare
      disease or for the off-label use of such agents in refractory inflammatory
      disorders.

PMID- 21906427
TI  - Ultrasound imaging for the rheumatologist XXXIV. Sonographic assessment of the
      painful foot.
AB  - The foot is increasingly the focus of attention for rheumatologists when
      assessing patients presenting to a clinic and may represent underlying intra
      articular inflammatory pathology or involvement of the surrounding soft tissues.
      This study describes the correlation between clinical and ultrasound (US)
      findings in patients presenting with a variety of rheumatic disorders linked with
      foot pain. Poor correlation was found between conventional clinical examination
      and US in cases with joint inflammation, tendonitis and, more particularly, those
      cases with enthesopathy.

PMID- 21906428
TI  - Efficacy of serum angiopoietin-1 measurement in the diagnosis of early rheumatoid
      arthritis.
AB  - OBJECTIVES: Previous studies showed that angiopoietin-1(Ang-1) expression was
      increased in the synovium in early rheumatoid arthritis (RA) patients. The
      present study was therefore designed to examine whether determination of serum
      Ang-1 might be effective in diagnosis of early RA. METHODS: One hundred and five
      serum samples of RA (21 males, 84 females) were studied for serum Ang-1 level.
      Serum samples were also collected from other collagen diseases, including 35
      cases of SLE, 29 cases of systemic sclerosis, 16 cases of
      polymyositis/dermatomyositis. Serum samples were additionally obtained from 34
      patients who visited our clinic for evaluation of symmetrical polyarthritis with
      morning stiffness. After one year of follow-up, those patients who satisfied the
      ACR 1987 classification criteria for RA were defined as 'early RA'. Serum Ang-1
      levels were measured by sandwich ELISA using anti-angiopoietin-1 antibodies (both
      monoclonal and polyclonal antibodies). Serum anti-CCP antibody and rheumatoid
      factor (RF) were measured by ELISA and by laser nepherometry, respectively.
      RESULTS: Serum Ang-1 in RA patients was significantly higher than those in other
      collagen diseases. Serum Ang-1 levels in 50 normal healthy individuals were 5.8
      +/- 0.31 pg/ml (mean +/- SEM). There was no significant difference in CRP and
      serum RF at the first visit between early RA patients and non-RA patients,
      whereas serum Ang-1 levels at the first visit were significantly higher in early
      RA (58.7 +/- 17.9 pg/ml [mean +/- SEM]) than those in non-RA (8.2 +/- 4.5 pg/ml).
      ROC analysis revealed that serum Ang-1 (cut-off 23.91 pg/ml) could diagnose early
      RA at sensitivity 57.1% and specificity 84.6%, providing comparable area under
      the curve (0.71, 95% CI: 0.54-0.88) to that of serum anti-CCP antibody (0.72, 95%
      CI: 0.53-0.92). There was no significant correlation between anti-CCP antibody
      and Ang-1. CONCLUSIONS: These results indicate that serum Ang-1 is as useful a
      marker for the diagnosis of early RA as serum anti-CCP antibody.

PMID- 21906429
TI  - Efficacy and safety of ultrasound-guided local injections of etanercept into
      entheses of ankylosing spondylitis patients with refractory Achilles enthesitis.
AB  - OBJECTIVES: Enthesitis is one of the most common and specific manifestations of
      ankylosing spondylitis (AS). However, the treatment of enthesitis is still a
      challenge for rheumatologist so far, especially to those AS patients with serious
      enthesitis. This study aimed to evaluate the efficacy and safety of ultrasound
      (US)-guided local injection of etanercept into entheses of AS patients with
      refractory Achilles enthesitis. METHODS: Twelve AS patients with severe
      unilateral refractory Achilles enthesitis were enrolled. Among them, 5 patients
      received US-guided local injection of etanercept and the other 7 received
      betamethasone. BASDAI, BASFI, VAS of the affected heel, the percentage of ASAS20
      responders, CRP, ESR and any adverse events were recorded at baseline, 2, 4, 8
      and 12 weeks after the treatment. US was also used to evaluate the corresponding
      entheses at baseline and every follow-up visit. RESULTS: The BASDAI, BASFI, VAS
      of the affected heel, CRP, ESR, the percentage of ASAS20 responders and the
      regional blood flow signals detected by colour Doppler were all improved in both
      the etanercept group and the betamethasone group, at each follow-up visit
      compared to the baseline data (p<0.05). There were no significant differences in
      the improvements of any of the above parameters between the two groups (p>0.05).
      In addition, there were no adverse events from the etanercept group, except for
      the mild acid bilges feeling during the injection procedure, while 1 patient from
      the betamethasone group developed mild local atrophoderma since the week 4 follow
      up visit and the atrophoderma kept stable at the 2 subsequent visits.
      CONCLUSIONS: US-guided local injection of etanercept might be a highly effective,
      safe and well tolerated treatment for Achilles enthesitis in patients with AS.

PMID- 21906430
TI  - Advanced glycation end products affect growth and function of osteoblasts.
AB  - OBJECTIVES: Advanced glycation end products (AGEs) have been implicated in the
      pathogenesis of bone-destructive disorders. Yet reports on the influence of AGEs
      on human osteoblasts remain lacking. The aim of the study is to investigate the
      influence of AGE-modified bovine serum albumin (AGE-BSA) on cell growth and
      expression of osteoblastic markers associated with osteogenesis and
      osteoclastogenesis. METHODS: Human osteoblasts established from bone tissue
      specimens were stimulated with AGE-BSA and investigated in vitro. Expression of
      mRNA for the receptor for AGEs (RAGE), nuclear factor kappa B subunit p65
      (NFkappaB p65), tumour necrosis factor alpha (TNF-alpha), matrix metallo
      proteinase-1 (MMP-1), receptor activator of NFkappaB ligand (RANKL),
      osteoprotegerin, collagen type I (Col1), osteocalcin (OC) and alkaline
      phosphatase (ALP) were measured using real-time polymerase chain reaction (PCR).
      Respective protein expressions were evaluated by western blot analysis or ELISA.
      NFkappaB activation was investigated by luciferase assay and electrophoretic
      mobility shift assay (EMSA). Cell cycle analysis, cell proliferation and markers
      of necrosis and early apoptosis were assessed. RESULTS: AGE-BSA was actively
      taken up into osteoblasts and induced cell cycle arrest and an increase in
      necrotic, but not apoptotic cells. The increased expression of RAGE and TNF-alpha
      together with NFkappaB activation indicates an AGE-mediated inflammatory
      response. The decreased expression of Col1, OC and ALP presumably reflects a
      diminished osteogenic potential, whereas upregulation of RANKL and TNF-alpha
      enhances osteoclastogenesis. CONCLUSIONS: The present study demonstrates that AGE
      BSA affects the growth and function of osteoblasts. Modulation of the expression
      of various target genes involved in bone metabolism provides evidence that AGEs
      accumulated in the bone matrix have the potential to suppress osteogenic and to
      promote osteoclastogenic properties of osteoblasts in vivo, thereby leading to
      functional and structural impairment of bone.

PMID- 21906431
TI  - The European ankylosing spondylitis infliximab cohort (EASIC): a European
      multicentre study of long term outcomes in patients with ankylosing spondylitis
      treated with infliximab.
AB  - OBJECTIVES: To study the long-term efficacy and safety of treatment with
      infliximab in patients with ankylosing spondylitis (AS) in a real life setting.
      METHODS: AS patients from 6 European countries who had finished the 2-year trial
      ASSERT were invited to participate in the open- label investigator-driven study
      EASIC. At baseline, 2 groups were formed: patients of group 1 had not been
      treated with infliximab after ASSERT, while those of group 2 had continuously
      received it. Patients of group 1 were further subdivided in group 1a: patients
      with a relapse and 1b: in remission. All patients of group 1a and 2 continuously
      received infliximab for 96 weeks, mean dose 5 mg/kg, intervals 6-8 weeks.
      Patients of group 1b were also treated in case of relapse. RESULTS: A total of
      103/149 patients (69%) were included in EASIC, 1.3 +/- 0.9 years after the end of
      ASSERT: 9 in group 1a, 5 in group 1b and 89 in group 2. Most patients were male
      (83%), mean age 44 years. Most patients of group 2 completed the trial (86%) vs.
      only 5 of group 1 (33%) - mostly due to allergic reactions after readministration
      of infliximab. In total, there were 22 drop-outs due to 6 adverse events, 4 lack
      of efficacy, 3 planned pregnancy. All standard assessments indicated beneficial
      values over time, at week 96 significantly better than at baseline of ASSERT.
      CONCLUSIONS: The majority of patients were continuously and successfully treated
      with infliximab for 5 years, whereas discontinuation and reintroduction of
      therapy was less satisfactory due to the frequent occurrence of hypersensitivity
      reactions. Anti-TNF therapy with infliximab proved to be effective and safe on a
      long-term basis.

PMID- 21906432
TI  - Lack of association of NAMPT rs9770242 and rs59744560 polymorphisms with disease
      susceptibility and cardiovascular risk in patients with rheumatoid arthritis.
AB  - OBJECTIVES: Visfatin is an adipokine encoded by the NAMPT (PBEF1) gene. In this
      study we assessed the potential association of two NAMPT gene polymorphisms with
      disease susceptibility and cardiovascular (CV) risk in patients with rheumatoid
      arthritis (RA). METHODS: A total of 1,395 patients fulfilling the 1987 ACR
      classification criteria for RA and 1,230 matched controls, were genotyped for the
      NAMPT rs9770242 and rs59744560 gene polymorphisms, located within the proximal
      promoter, using predesigned TaqMan single nucleotide polymorphism genotyping
      assay. Also, HLA-DRB1 genotyping was performed using molecular based methods. In
      a second step, 1,196 patients in whom full information was available were
      assessed to determine the influence of NAMPT rs9770242 and rs59744560
      polymorphisms in the development of CV events. Also, the potential influence of
      these polymorphisms in the development of subclinical atherosclerosis was
      assessed in a subgroup of patients with no history of CV events by brachial
      artery reactivity to determine flow-mediated endothelium-dependent and
      endothelium-independent vasodilatation (n=125) and by B-mode ultrasonography to
      determine the carotid artery intima-media thickness (n=105). RESULTS: No
      statistically significant differences in the allele or genotype frequencies for
      the NAMPT gene polymorphisms between RA patients and controls were found. A
      modest non significant lower frequency of the minor allele G of rs9770242
      polymorphism was observed among patients with CV disease (20.62%) compared to
      those without CV disease (22.83%) (p=0.39). Also, a slight nonsignificant lower
      frequency of the minor allele T of rs59744560 polymorphism in patients with CV
      events (9.81%) compared with those RA patients who did not experience CV disease
      (13.07%) (p=0.11) was observed. Likewise, no significant association between the
      NAMPT polymorphisms with surrogate markers of subclinical atherosclerosis was
      found in patients with RA. CONCLUSIONS: NAMPT rs9770242 and rs59744560
      polymorphisms are not markers of disease susceptibility and CV disease in RA.

PMID- 21906433
TI  - Rapid growing mycobacteria and TNF-alpha blockers: case report of a fatal lung
      infection with Mycobacterium abscessus in a patient treated with infliximab, and
      literature review.
AB  - Rapid growing mycobacteria pose as a serious emerging threat for patients treated
      with TNF-alpha blockers. We report a case of a progressive and fatal pulmonary
      infection with M. abscessus in a patient previously treated with infliximab for
      Crohn's disease and review seven other previously reported patients. Five out of
      eight patients were female. The patients were treated with either anti-TNF-alpha
      antibodies or TNF-alpha blocking receptor. The diagnosis of RGM came in the first
      6 months after initiation of TNF-alpha blockers in five out eight patients. The
      two patients with M. abscessus lung infection died in spite of antibiotic
      treatment, whereas the other patients with skin affection and lever affection due
      to M. Fortuitum had a resolution of their symptoms with discontinuation of TNF
      alpha blockers and antibiotics.

PMID- 21906434
TI  - Bacille Calmette Guerin (BCG) can induce Kawasaki disease-like features in
      programmed death-1 (PD-1) gene knockout mice.
AB  - OBJECTIVES: Various genetic variants of inhibitory immune signals have been
      suspected as feasible causes of Kawasaki disease (KD). We investigated the
      associative role of programmed death-1 (PD-1) gene in the pathogenesis of KD by
      injecting bacilli Calmette Guerin (BCG) to PD-1 gene knockout (PD-1KO) mice.
      METHODS: In order to induce KD-like clinical manifestations in young PD-1KO mice,
      intradermal injection of the bacilli Calmette Guerin (BCG) was performed twice on
      the abdominal skin with a 4-week interval. For defining the role of BCG, heat
      shock protein (HSP) 65 was challenged. In addition, Staphylococcus aureus was
      adopted as a microorganism that does not contain HSP65 structure. One month after
      the second injection, heart, liver, and kidneys were removed and examined.
      RESULTS: PD-1KO mice showed KD-like features including prolonged fever for more
      than 5 days, erythematous swelling on soles, tail skin desquamation, and
      gallbladder (GB) hydrops. Inflammatory cell aggregation and intimal proliferation
      in at least more than one coronary artery was found in all PD-1KO mice whereas
      scanty coronary lesion was found in wild type (WT) mice. When the PD-1KO mice
      were injected twice with HSP65, coronary arterial lesions similar to those seen
      after BCG injection were observed. Inflammatory reactions in other organs
      including hepatic arteries, renal arteries, and biliary arteries were also
      observed in PD-1KO mice. CONCLUSIONS: Our data suggest that PD-1 gene may be one
      of the genetic predispositions of KD and antigens containing HSP65 structure
      could be a triggering factor of KD by our animal model of KD.

PMID- 21906435
TI  - Association of small ubiquitin-like modifier 4 gene polymorphisms with rheumatoid
      arthritis in a Tunisian population.

PMID- 21906437
TI  - Platelet-rich plasma (PRP) intra-articular ultrasound-guided injections as a
      possible treatment for hip osteoarthritis: a pilot study.

PMID- 21906436
TI  - Efficacy of rituximab on pulmonary nodulosis occurring or increasing in patients
      with rheumatoid arthritis during anti-TNF-?alpha therapy.

PMID- 21906438
TI  - Atlanto-axial joint involvement as exclusive manifestation of juvenile idiopathic
      arthritis (JIA).

PMID- 21906439
TI  - [Bio panning of human stem cell factor(2) mimetic peptides from phage displayed
      random peptide library].
AB  - OBJECTIVE: To screen human stem cell factor (hSCF) mimetic peptides in vitro with
      a phage-display random peptide library. METHODS: Phage clones with high hSCF
      receptor (rc-kit/Ig 1-3)-binding activity was screened from phage-displayed
      random hepta/dodecapeptide library by phage enzyme-linked immunosorbent assay
      (ELISA). Phage single DNA was extracted and sequenced. Four kinds of peptide with
      higher c-Kit/Ig 1-3 binding activity were chosen for synthesis and characterized
      by using cell proliferation assay with 3-(4,5-dimethylthiazol-2-yl)2,5
      diphenyltetrazolium bromide (MTT) method in UT-7 cells. RESULTS: Eleven Ph.D.-C7C
      clones and eight Ph.D-12 phage clones with high hSCF receptor-binding activity
      were selected from phage-displayed random hepta/dodecapeptide library,
      respectively. Sequence analysis showed there were no homologous sequence between
      hSCF and these screened mimetic peptides except one homologous sequence DPSPHTH
      found in heptapeptide library. All these four synthesized peptides (CE3, CE16,
      LE4, and LE20), particularly CE16 and LE20, stimulated UT-7 cell proliferation.
      CONCLUSION: Four hSCF mimetic peptides were successfully isolated from phage
      displayed random peptide library..

PMID- 21906440
TI  - [Effect of endemic fluoride poisoning caused by coal burning on the oxidative
      stress in rat testis].
AB  - OBJECTIVE: To explore the effect of endemic fluoride poisoning caused by coal
      burning on the oxidative stress in rat testis. METHODS: Totally 40 male SD rats
      were equally randomized into four groups control group, low fluorosis group,
      middle fluorosis group, and high fluorosis group. Rats in all three fluorosis
      groups were fed with corn dried by burning coal obtained from endemic fluorosis
      areas with high fluoride, and thus the animal models of fluorosis were
      established. After 120 and 180 days, all the rats were sacrificed. Testis tissues
      were stained with hematoxylin eosin and observed under light microscope. The
      malonaldehyde (MDA) content, superoxide dismutase (SOD) activity, total nitric
      oxide synthase (TNOS), and inducible nitric oxidase synthase (iNOS) were measured
      by biochemical methods in the testis tissues. The content of NaF in testis was
      measured by fluorine selective electrode. RESULTS: The rat fluorosis models were
      successfully established. The fluoride content in testis was significantly
      increased in all the fluorosis groups(P<0.01). Testicular structures were damaged
      in all of fluoride groups. The TNOS, iNOS activities, and MDA content of each
      fluoride group were significantly higher than that of the control group on day
      120 and 180 (P<0.05 or 0.01 ). The TNOS, iNOS activities, and MDA content
      significantly increased in a dose dependent manner (P<0.05 or 0.01). The SOD
      activities significantly decreased in all the fluoride groups (P<0.05 or 0.01).
      CONCLUSIONS: Endemic fluoride poisoning caused by coal burning can cause
      disorders in the oxidative system and antioxidative system in rat testis. The
      oxidative stress may play an important role in the fluorides induced reproductive
      toxicity in male rats.

PMID- 21906441
TI  - [Association between the polymorphisms of cluster of differentiation 14 gene
      promoters and the susceptibility of multiple organ dysfunction syndrome after
      severe chest trauma].
AB  - OBJECTIVE: To investigate the polymorphisms of cluster of differentiation
      14(CD14)gene promoters and explore whether such polymorphisms are associated with
      the susceptibility to multiple organ dysfunction syndrome(MODS) in Chongqing
      population. METHODS: The single nucleotide polymorphisms of the promoter region
      of CD14 gene at position -1145 and -159 were detected using polymerase chain
      reaction-restriction fragment length polymorphism method in 106 patients with
      severe chest trauma, among whom 47 were with MODS. RESULTS: Trauma patients
      carrying G allele tended to have a higher risk of MODS than those carrying A
      allele at position-1145, the MODS scores in trauma patients carrying G allele
      were significantly higher than those carrying A allele (P=0.217 for dominant
      effect and P=0.037 for recessive effect), and the MODS scores in trauma patients
      carrying T allele were significantly higher than those carrying C allele at
      position -159 (P=0.048 for dominant effect and P=0.198 for recessive effect). The
      genotypes of CD14 gene at positions -1145 and -159 were significantly correlated
      with the MODS scores (P=0.043,P=0.046). Compare with single-point mutation,
      simultaneous two-point mutation had significantly higher risk of MODS (Pu0.01),
      while the difference of MODS scores showed no statistical significance (P=0.239).
      CONCLUSION: The polymorphisms of CD14 gene promoters are associated with MODS
      after severe chest trauma in Chongqing population.

PMID- 21906442
TI  - [Combination of AD5-10 and epirubicin in treating rheumatoid arthritis].
AB  - OBJECTIVE: To investigate the mechanism of anti-death receptor 5-10 (AD5-10)
      combined with epirubicin in treating rheumatoid arthritis (RA). METHODS: We
      detected the cell viability of the fibroblast-like synoviocytes (FLS) from RA
      patients with MTT. The expression level of apoptosis signaling pathways protein,
      p53, and p21 were evaluated with Western blot. RESULTS: We found that epirubicin,
      at different doses, could enhance the effect of AD5-10 on FLS, promoting the
      apoptosis of FLS. The expression levels of caspase-3, -8, -9, c-FLIP, Bcl-2, p53,
      and p21 in the FLS changed after epirubicin treatment. CONCLUSION: Epirubicin may
      coordinate with AD5-10 in inducing FLS apoptosis through affecting the levels of
      p53, p21, c-FLIP, and Bcl-2.

PMID- 21906443
TI  - [Effect of phospholipomannan of Candida albicans on the production of interleukin
      6 and interleukin 8 in monocytes].
AB  - OBJECTIVE: To investigate whether Candida albicans-native phospholipomannan (PLM)
      induce an inflammation response through Toll-like receptor(TLRe2 in human acute
      monocytic leukemia cell line (THP-1) cells. METHODS: Human THP-1 monocytes were
      challenged with PLM in vitro. The mRNA expressions of TLR2, TLR4, proinflammatory
      cytokine [interleukin(IL)-6], and chemokine (IL-8) were assayed by real time
      reverse transcription polymerase chain reaction. The secretions of IL-6 and IL-8
      were measured by enzyme-linked immunosorbent assay. The expression of TLR2 was
      analyzed with Western blot. RESULTS: PLM increased the mRNA expressions and
      secretions of proinflammatory cytokines (IL-6) and chemokines (IL-8) in THP-1
      cells (all P=0.0000). PLM up-regulated the mRNA and protein levels of TLR2
      (P=0.0000), whereas the mRNA level of TLR4 was not altered. PLM hydrolyzed with
      beta-D-mannoside manno hydrolase failed to induce gene and protein expressions of
      TLR2, IL-6, and IL-8. Anti-TLRS-neutralizing antibody blocked the PLM-induced
      secretions of IL-6 and IL-8 in THP-1 cells (P = 0.0003, P = 0.0010). CONCLUSION:
      Canidada albicans-native PLM may contribute to the inflammatory responses during
      Candida infection in a TLR2-dependent manner.

PMID- 21906444
TI  - [A new animal model of osteonecrosis induced by focal alternative cooling and
      heating insults].
AB  - OBJECTIVE: To establish a new animal model of osteonecrosis of the femoral
      head(ONFH) with improved consistency and incidence of femoral head collapse for
      studies on the mechanism of osteonecrosis. and on the assessment of treatment
      effectiveness. METHODS: Twenty adult male emus were used. Guide instrumentation
      was constructed to position the customized probe just articularly and at the
      proximal part of the femoral head. An alternating focal liquid nitrogen freezing
      and radiofrequency heating was applied. At 2, 4, 8, 12 and 16 weeks after
      surgery, hip magnetic resonance imaging (MRI) was performed. Before the emus were
      sacrificed, barium sulfate was infused to lower extremities for microangiography.
      The femoral samples were scanned by micro-computed tomography (Micro-CT) and
      evaluated histologically. RESULTS: No bird demonstrated signs of infection or
      died unexpectedly. Hip MRI showed changes massive edema at the 4th week,
      increasingly localized abnormal signals at the 8th'" week, and femoral head
      collapse at the 12'h week. Micro-CT scans and histological images at the 16th
      week showed human-like osteonecrotic changes with impaired local blood supply.
      Bone mineral density of the collapsed head was (380. 31 + 28. 12) mg/cm3 and
      trabecular spaces were (0. 86 +/-0.32) mm; both were significantly lower than
      those in the control side, which were (415.75 41.28) mg/cm3 and (1. 17 +/- 0. 17)
      mm, respectively (P < 0. 05). Bone volume fraction of the collapsed head
      was(47.28 +/- 17. 14)% and trabecular thickness was (506. 17 +/- 220. 58) p.m;
      both were significantly higher than those at control side, which were (30. 92 +/-
      4. 01)% and (325. 50 +/-44. 53) pm, respectively (P <0. 05). The microangiography
      at the 16th week showed that vessel volume fraction was (0. 315 +/- 0. 055)% ,
      which was significantly higher than the collapsed side [ (0. 142 +/- 0. 059)% ]
      (P <0. 05). CONCLUSIONS: The emu model of fem-oral head osteonecrosis was
      successfully established using focal alternating cooling and heating insults. The
      models, with improved consistency and incidence of femoral head collapse, can be
      used in studies on the mechanism of osteonecrosis and on the assessment of
      treatment effectiveness.

PMID- 21906445
TI  - [Biological features and ultrastructure of human umbilical cord mesenchymal stem
      cells].
AB  - OBJECTIVE: To isolate and culture human umbilical cord mesenchymal stem cells
      (MSCs) and explore their biological features and ultrastructure. METHODS: After
      isolating MSCs from the human umbilical cord, the proliferation, cycle, and
      apoptosis were observed. The cell ultrastructure was observed under transmission
      electron microscope. The cytokines including vascular endothelial growth factor
      (VEGF), hepatocyte growth factor (HGF), and insulin-like growth factor-1 (IGF-1)
      were detected using enzyme-linked immunosorbent assay. RESULTS: Human umbilical
      cord MSCs had fibroblast-like morphology and increased proliferation capability.
      Ultrastructural analysis showed that the MSCs had active cellular metabolism and
      strong migration and differentiation capabilities. Meanwhile, they could secrete
      anti-apoptotic cytokines such as VEGF, IGF-1, and HGF. CONCLUSION: Human
      umbilical cord MSCs can secrete many anti-apoptotic cytokine and have good
      biological features.

PMID- 21906446
TI  - [Application of enriched bone marrow compound with fibrin glue in repairing old
      radial bone defect in rabbits].
AB  - OBJECTIVE: To explore the feasibility of using enriched bone marrow (BM) compound
      with fibrin glue (FG) in repairing old radial bone defect. METHODS: Totally 36
      New Zealand rabbits were equally randomized into three groups: simple FG group,
      BM+FG group, and enriched BM+FG group. A 1.5-cm segmental bone defect was made at
      the left radial in each animal. After one month, the defect was implanted with
      the engineered bone. Before implantation, a compound of enriched BM with FG
      underwent electron microscopy, long-term culture, and bacteriological culture.
      Four, 8, and 12 weeks after operations, the osteogenetic effect was evaluated
      using X-ray observation, HE staining, or Van Gieson staining, and a semi
      quantitative analysis was performed. RESULTS: Electron microscopy showed enriched
      BM were compatible well with FG. No bacterial contamination or oncogenicity was
      observed after long-term culture. X-ray showed the repair effectiveness was
      significantly higher in BM+FG group and enriched BM+FG group than in simple FG
      group. Eight and 12 weeks after surgery, the Yang scores were significantly
      higher in enriched BM+FG group than in BM+FG group [(9.348+/-0.364evs.(7.984+/
      0.229eiF=40.167iP=0.001; (12.664+/-0.388)vs. (10.584+/-0.836e,
      F=20.3647iP=0.004]. In addition, the Yang's scores at bone defects in BM+FG group
      and enriched BM+FG group were higher at the 12(th) week than in the 8(th) week.
      (F=36.004iP=0.001; F=155.141iP=0.000; respectively)The bone defects were repaired
      at varied degrees were histologically observed in BM+FG group and enriched BM+FG
      group during the observations. CONCLUSION: Implantation of BM+FG or enriched
      BM+FG are effective in repairing old radial bone defects, while simple FG shows
      not such effect.

PMID- 21906447
TI  - [Expressions of receptor tyrosine kinases mRNA and protein in carcinoma of
      bladder].
AB  - OBJECTIVE: To detect the expressions of receptor tyrosine kinases (RTKs) mRNA and
      protein and to explore potentially promising tumor markers and conceivable drug
      target in bladder cancer. METHODS: The expressions of RTKs mRNA and protein in
      tissue from invasive urothelial carcinoma of the bladder were examined by real
      time quantitative PCR array and cytokine antibody array, with normal bladder
      tissue as control. The Results were analyzed using bioinformatic approaches.
      RESULTS: The expressions of TGFA, STAB1, SERPINE1, ANGPT2, SPINK5, ANGPTL1,
      PROK1, MDK, CXCL9, GRN, RUNX1, VEGFA, and TGFB1 were obviously upregulated in
      bladder cancer tissue, while those of EDIL3, PTN, CCL2, PDGFD, FGF13, KITLG,
      FGF2, SERPINF1, and TNF were downregulated. ALK, Btk, EphB2, ErbB4, PDGFR-alpha,
      ROS, Tie-2, Tyk2, and VEGFR3 were over-expressed in bladder cancer, while FRK,
      Fyn, IGF-IR, Insulin R, Itk, JAK1, JAK3, and LCK were low-expressed. CONCLUSION:
      Vascular endothelial growth factor/platelet-derived growth factor-targeted
      therapies may play an active role in treating carcinoma of bladder.

PMID- 21906448
TI  - [Polymorphism of 17 short tandem repeat Loci of Tibetan minority ethnic group
      from Lhasa].
AB  - OBJECTIVE: To investigate the polymorphism of 17 short tandem repeat (STR) loci
      of Tibetan minority ethnic group from Lhasa. METHODS: Blood samples were obtained
      from 132 unrelated Tibetan individuals from Lhasa. DNA templates were screened by
      home-made AGCU17+1 kit and 3130XL genetic analyzer. Genotyping was performed
      using GeneMapper software (version 3.2). RESULTS: The allele frequencies of 17
      STR loci ranged 0.0038-0.5720, and the power of discrimination ranged 0.779
      0.979, the power of exclusion ranged 0.327-0.737, the polymorphism information
      contents ranged 0.538-0.910, and the heterozygosity ranged 0.629-0.871. The
      cumulative coupling probability was 3.93 * 10(-20), and the cumulative power of
      exclusion was 0.9999995234. Of 17 STR loci, Penta E and D6S1043 had the highest
      polymorphism indicators, while TPOX had the lowest. CONCLUSION: The 17 STR loci
      used in this study are highly polymorphism in Tibetan minority ethnic group from
      Lhasa and fit for the population genetic study and forensic cases.

PMID- 21906449
TI  - [Application of melanocytes and bone marrow mesenchymal stem cells in tissue
      engineered skin construction].
AB  - OBJECTIVE: To explore the method of constructing tissue-engineered skin using
      melanocytes and bone marrow mesenchymal stem cells (BMSCs) in vivo. METHODS:
      Melanocytes were isolated from human foreskin. BMSCs were isolated from human
      bone marrow. Both of them were co-cultured at a ratio of 1:10, and then were
      implanted into the collagen membrane to construct the tissue-engineered skin,
      which was applied for wound repair in nude mice. The effectiveness of wound
      repair and the distribution of melanocytes were evaluated by morphological
      observation, in vivo 4,6-diamidino-2-phenylindole, dihydrochloride (DAPI)
      fluorescent staining tracing, HE staining, S-100 immunohistochemistry, and
      transmission electron microscopy. RESULTS: The wounds were satisfactorily
      repaired among the nude mice. The melanocytes were distributed in the skin with
      normal structure, as confirmed by DAPI fluorescent staining tracing, HE staining,
      S-100 immunohistochemistry, and transmission electron microscopy. CONCLUSION:
      Melanocytes and BMSCs, after proper in vitro culture at an appropriate ratio, can
      construct the tissue-engineered skin with I type collagen membrane.

PMID- 21906450
TI  - [Estrogen induced rat model of uterine leiomyoma].
AB  - OBJECTIVE: To establish an appropriate animal model of uterine leiomyoma and to
      understand the pathogenesis of this disease. METHODS: Mature female rats were
      intramuscularly injected with estradiol benzoate at 200 MUg or 300 MUg twice a
      week. After injection for 8 or 10 weeks, the rats were sacrificed. We measured
      the serum levels of estrogen (E(2)) and progesterone (P), evaluated ER and PR
      expression, and calculated the leiomyoma forming rate and mortality of the rats.
      Histological changes were compared between rat uterine leiomyoma and human
      uterine leiomyoma with HE staining. The optimal dose and duration of E(2) for
      induction of uterine leiomyoma in rat were determined. RESULTS: In the rats
      treated with estradiol benzoate 200 MUg for 8 weeks in the serum E(2) level
      increased significantly (P<0.01). Uterine nodules were visible in some of the
      tested rats. Based on the pathohistological Results , the uterine leiomyoma
      developed in the treated rats demonstrated similar features as in human uterine
      leiomyoma. The expressions of ER and PR were increased in the leiomyoma tissues.
      CONCLUSION: The rat model of uterine leiomyoma can be established by
      intramuscular injection of estradiol benzoate at 200 MUg twice per week for 8
      weeks, with similar features as those of human uterine leiomyoma. The high
      concentrations of ER and PR in uterine tissue might be related with the
      development of uterine leiomyoma in animal.

PMID- 21906451
TI  - [Prevention of platelet transfusion refractoriness and HLA alloimmunization by
      leukocyte filtered platelet transfusion: a meta analysis].
AB  - OBJECTIVE: To compare and assess the effectiveness of leukocyte-filtered platelet
      and standard platelet concentrates transfusion in preventing platelet transfusion
      refractoriness (PTR) and human leukocyte antigen (HLA)-alloimmunization. METHODS:
      Randomized controlled trials (RCTs) or quasi-RCTs comparing leukocyte-filtered
      platelet with standard platelet concentrates transfusion (up to December 31,
      2009) were searched and identified from Medline, EMBASE, The Cochrane Library,
      and CBM. A meta-analysis was conducted with Cochrane Collaboration's RevMan 5. 0.
      RESULTS: The search identified 558 citations in total, in which 7 articles in
      English were finally included in the meta-analysis. The analysis showed that
      compared with standard platelet concentrates transfusion, leukocyte-filtered
      platelet transfusion significantly decreased PTR [ RR = 0. 59, 95% CI (0. 42, 0.
      82) , P = 0. 002 ] and HLA-alloimmunization [ RR = 0. 49,95% CI (0. 33, 0. 74) ,
      P =0. 0006]. Subgroup analysis showed that HLA-alloimmunization was significantly
      reduced by leukocyte-filtered platelet transfusion among the patients with acute
      myelocytic leukemia [ RR =0.42, 95% CI (0.32, 0.56), P <0. 00001], while no
      significant difference was detected in patients with acute lymphoblastic leukemia
      because of the limited sample size [ RR = 0. 50, 95% CI (0. 10, 2.41) , P =0.
      39]. CONCLUSIONS: The current evidence shows that leukocyte-filtered platelet
      transfusion can prevent PTR and HLA-alloimmunization more effectively than
      standard platelet transfusion. Well-designed large-scale RCTs are still needed to
      further confirm this finding.

PMID- 21906453
TI  - [Clinical significance of tissue factor and vascular endothelial growth factor
      expressions on CD14+ monocytes in patients with non Hodgkin lymphoma].
AB  - OBJECTIVE: To explore the values of tissue factor (TF) and vascular endothelial
      growth factor (VEGF) expressions on peripheral CD14+ monocytes in disease
      assessment, prognosis, and short-term efficacy evaluation of non-Hodgkin lymphoma
      (NHL) patients. METHODS: TF and VEGF expressions on CD14+monocytes in 47 NHL
      patients (disease group) before chemotherapy and after 4 chemotherapy cycles and
      in 30 healthy subjects (control group) were detected by flow cytometry, and the
      potential relationship among TF, VEGF, International Prognostic Index (IPI), and
      short-term efficacy were analyzed. RESULTS: TF and VEGF expressions on CD14 +
      monocytes in disease group were significantly higher than those in control group
      ( all P <0. 01) and positive correlation was showed between them (r = 0. 708, P =
      0.00). TF and VEGF expressions in Ann Arbor stage III and IV (n = 22 and 19) ,
      symptomatic (n = 22) , lactate dehydrogenase (LDH) increased (n = 21) , Eastern
      Cooperative Oncology Group (ECOG) score 2-4 (n = 12) and extranodal lesions >1 (n
      = 16) groups were significantly higher than those in Ann Arbor stage II (an = 6)
      , asymptomatic (an =25) , LDH normal (n = 26) , ECOG score 0-1 ( n = 35) and
      extranodal lesions ~1 ( na = 31) groups, respectively (all P <0.05). The
      expressions of TF and VEGF on CD14 + monocytes in high-risk (n = 7) or high
      middle-risk (n = 11) groups were significantly increased compared with low-risk
      (n = 15) or low-middle-risk(n = 14) groups, respectively (all P <0. 01). TF and
      VEGF expressions in non-remission group before chemotherapy (n = 11) were both
      obviously higher than those in remission group (an = 36, all P <0. 01) , and
      after chemotherapy their expressions in remission group were significantly lower
      than those before chemotherapy (all P <0. 01) , while such significant changes
      were not observed in the non-remission group ( all P > 0. 05). CONCLUSION: The
      high expressions of TF and VEGF on peripheral CD14 + monocytes can be useful
      markers in dis-ease assessment, prognosis evaluation and short-term efficacy
      observation of NHL patients.

PMID- 21906452
TI  - [Change in body compositions in female patients with human immunodeficiency virus
      related lipodystrophy syndrome].
AB  - OBJECTIVE: To study the changes of body composition in females patients with
      human immunodeficiency virus (HIV)-related lipodystrophy (LD) syndrome (HIV-LD).
      METHODS: Totally 25 female patients who were treated in our hospital from January
      2002 to December 2009 were divided into LD group and non-LD group based on the
      existence of LD. All these patients were receiving highly active antiretroviral
      therapy (HAART). In addition, 12 healthy women were set as the controls. Total
      and regional body composition were measured by dual X-ray absorptiometry in all
      three groups. RESULTS: The fat mass (FM) was correlated negatively with the
      duration of HAART (r=-0.431, P=0.029). Multiple linear regression analysis showed
      that FM had positive correlation with weight and negative correlation with lean
      mass (LM) (r = - 0. 973, P =0. 000). Total, trunk and leg FM were significantly
      lower in LD patients than that in controls (P <0.05).Meanwhile, total, trunk and
      leg bone mineral contents were statistically lower in LD patients than that in
      controls (P <0. 05). Lumbar bone mineral density of LD patients was lower than
      that of non-LD patients and controls, and there was significant difference
      between LD patients and controls (P = 0. 001). LM of LD patients was higher than
      that of non-LD patients but without statistical difference (P > 0. 05).
      CONCLUSIONS: The peripheral and central FM and bone mineral contents remarkably
      decrease in female patients with HIV-LD. How-ever, HIV-LD patients tend to have
      higher LM than non-LD patients. .

PMID- 21906454
TI  - [Clinical analysis of anti glomerular basement membrane disease with normal renal
      function].
AB  - OBJECTIVE: To investigate the clinical and pathologic characteristics of anti
      glomerular basement membrane(GBM) disease with normal renal function. METHODS:
      The clinical and pathologic data of 6 patients with anti-GBM disease and normal
      renal function in Peking Union Medical College Hospital were reviewed
      retrospectively. Furthermore, 29 patients with anti-GBM disease and impaired
      renal function in the same period in the same hospital were enrolled as the
      control group. Factors that may influence the prognosis were analyzed. RESULTS:
      Six (17.1%) of all 35 patients maintained normal renal function for 12-133 months
      during follow-up. Five patients had microhematuria and proteinuria, one had
      pulmonary hemorrhage only, and three manifested as Goodpasture syndrome. Renal
      biopsies from 4 patients revealed linear deposition of IgG 2+-3+ along the
      glomerular capillary walls by immunofluorescence. As shown by normal light
      microscopy, mild mesangial proliferation and crescentic glomerulonephritis with a
      large amount of fibrinoid necrosis of glomerular capillary walls were observed in
      different patients; however, most pathological changes were mild. Five of these
      six patients were treated with immunosuppressive drugs and/or plasma exchange.
      Compared with the control group, the 6 patients with normal renal function had
      significantly higher hemoglobin[(77.97+/-20.62 vs.(99.67+/-19.80 g/L P=0.024],
      lower titers of anti-GBM antibody[(224.34 +/- 145.79 vs.(80.23 +/- 85.73 EU/ml
      P=0.027], and lower ratio of glomeruli with crescents[(0.58+/-0.29 vs.(0.17+/
      0.27 ,P=0.005]. These 6 patients with normal renal function were followed up for
      12-133 months, among whom 4 patients achieved complete remission and 2 had mild
      proteinuria and microhematuria. CONCLUSION: Anti-GBM disease with normal renal
      function is not uncommon. Most patients have mild pathologic changes and good
      prognosis.

PMID- 21906455
TI  - [Short term clinical outcomes of laparoscopic fertility preserving radical
      hysterectomy in the management of early stage cervical cancer].
AB  - OBJECTIVE: To investigate the feasibility and effectiveness of laparoscopic
      radical trachelectomy and lymphadenectomy in the treatment of early-stage
      cervical cancer. METHODS: The clinical data of 6 patients (stage 1a2 to 1b1), who
      underwent laparoscopic fertility-preserving radical operation for cervical cancer
      in our department from February 2009 to October 2010, were retrospectively
      analyzed in terms of operation duration, intra-operative blood loss,
      postoperative pathology, complications, and pregnancy. RESULTS: Both radical
      resection of cervical and pelvic lymph node dissection were completed under
      laparoscopy, and only the cervical and vaginal cuffs were closed from vagina. The
      operation duration ranged 155-210 min (mean: 185 min) and the intra-operative
      blood loss was approximately 60-120 ml(mean: 105 ml). The average length of
      hospital stay was 18 days without complications, postoperative infection, and
      bleeding. Postoperative pathology showed no lymph node metastasis, and no
      ligament, blood vessels, vaginal cutting margin, or upper part of cervix was
      invaded by tumor cells. During the 8-20-month follow-up, 1 patient had become
      pregnant for 4 months and no case experienced tumor recurrence. CONCLUSION:
      Laparoscopic fertility-preserving lymphadenectomy and radical trachelectomy is
      feasible for patients with early-stage cervical cancer who have strong wish to
      have a child.

PMID- 21906456
TI  - [Induction of tracheal intubation without muscle relaxant by target controlled
      infusion of propofol combined with remifentanil in children].
AB  - OBJECTIVE: To observe the safety and feasibility of tracheal intubation by target
      controlled infusion of propofol and remifentanil without muscle relaxant in
      children. METHODS: Totally 100 4-10-year-old pediatric patients (ASA1) who had
      been scheduled for plastic surgery were equally divided into remifentanil group
      and control group through computer-generated randomized grouping. In all
      patients, five minutes after intravenous administration of atropine 0.01 mg/kg
      and midazolam 0.1 mg/kg, propofol was infused at the targeted effect-site
      concentration (Ce of 6 MUg/ml. When the intended target Ce of propofol was
      reached, the remifentanil group began to be infused with remifentanil at a Ce of
      5 ng/ml, and normal saline (0.1 ml/kg) was injected simultaneously. In the
      control group remifentanil was replaced by normal saline and rocuronium (0.8
      mg/kg) was injected together with the normal saline. After the equilibration of
      plasma and the Ce of remifentanil were reached, tracheal intubation was
      attempted. The complications during the induction and tracheal intubation were
      recorded. The intubating conditions were assessed using a five-point scoring
      system based on ease of laryngoscopy, vocal cords position, coughing, jaw
      relaxation and limb movement. RESULTS: The success rate of tracheal intubation
      was in 90% in remifentanil group and 98% in the control group
      (P=0.122).CONCLUSION Target-controlled infusion of propofol and remifentanil at
      Ce of 6 MUg/ml and 5 ng/ml is feasible for the induction and tracheal intubation
      without muscle relaxant in children.

PMID- 21906457
TI  - [Preventive efficacy of ondansetron and granisetron for postoperative nausea and
      vomiting in high risk patients].
AB  - OBJECTIVE: To compare the efficacy of ondansetron and granisetron in the
      prevention of postoperative nausea and vomiting (PONV) in high-risk patients.
      METHODS: Totally 200 patients with three key risk factors for PONV (female, non
      smoking and postoperative opioid use) were equally randomized into ondansetron
      group and granisetron group. Ondansetron (4 mg) or granisetron (3 mg) was
      intravenously administered upon the completion of surgery. The episodes of nausea
      and vomiting were observed for 24 hours after surgery. RESULTS: A significantly
      greater proportion of patients in granisetron group achieved a complete response
      (i.e., no PONV or rescue medication) during the first 24 hours postoperatively
      versus those in ondansetron group (62.6% vs. 46.9%, respectively; P=0.048). There
      were no significant differences in terms of postoperative nausea incidences
      (42.9% vs. 34.3%, respectively), postoperative vomiting incidences (25.5% vs.
      20.2%, respectively) and postoperative rescue anti-emetics incidences (19.4% vs.
      15.2%, respectively) (P>0.05). CONCLUSION: Granisetron is more effective than
      ondansetron in preventing PONV in high-risk patients during the first 24 hours
      postoperatively.

PMID- 21906458
TI  - [Research advances in induced pluripotent stem cells].
AB  - Differentiated somatic cells can be directly reprogrammed into induced
      pluripotent stem (iPS) cells in vitro. Similarly to embryonic stem (ES) cells,
      iPS cells have pluripotency to differentiate into all cell types and capability
      to self-renew themselves indefinitely. Without immune rejection and ethical
      issues, patient-specific iPS cells promise to be an ideal tool for regenerative
      medicine, drug screening, and toxicity testing.

PMID- 21906459
TI  - [Vasculogenic mimicry and mosaic vessels and targeted therapy in renal cell
      carcinoma].
AB  - Renal cell carcinoma is one of the most common malignant tumors of urinary
      system. The annual incidence rate is approximately 17.9/100 000 populations, and
      there is a continually rising trend in number of new diagnosis. Metastatic and
      high-risk renal cell cancer is associated with a poor prognosis and is resistant
      to traditional chemotherapy and/or radiotherapy. Although cytokine-based
      therapies (interferon and interleukin-2) have been widely used, their
      effectiveness remained unsatisfactory due to their low response rates and short
      survival. Drugs targeting anti-angiogenesis pathways have shown benefits in
      relapse-free survival. In this review, we introduce the recent advances in the
      treatment of renal cancer, especially the application of vasculogenic mimicry and
      mosaic vessels. Although targeted therapies with anti-angiogenic properties have
      proposed new treatment criteria for advanced renal cell carcinoma, new drugs or
      new combinations are needed to improve the clinical efficacy and minimize adverse
      effects.

PMID- 21906460
TI  - [Metabolic disorder after androgen deprivation therapy in patients with prostate
      cancer].
AB  - The prevalence of prostate cancer, a common malignancy of urinary system in
      elderly males, has increased rapidly in China in recent years. Currently most
      prostate cancer patients are treated with androgen deprivation therapy (ADT).
      However, ADT-induced metabolic disorders such as metabolic syndrome has
      remarkably impaired the quality of life and decreased the survival rate.

PMID- 21906461
TI  - [Subcutaneous implanted system for the treatment of type 2 diabetes].
AB  - Type 2 diabetes is a complex metabolic disorder characterized by hyperglycemia
      arising from a combination of insufficient insulin secretion and resistance to
      insulin action. Insulin has become an important agent in treating this disease,
      but long-term administration of insulin not only brings pain and inconvenience to
      the patients but also causes local adipose tissue atrophy and scleroma.
      Therefore, novel delivery method has become a hot topic, mainly including
      improving delivery systems, developing new recombinant insulin, and changing the
      route of administration. This article introduces DUROS (an implanted delivery
      system), a new route of drug administration.

PMID- 21906462
TI  - The clinical effectiveness and cost-effectiveness of genotyping for CYP2D6 for
      the management of women with breast cancer treated with tamoxifen: a systematic
      review.
AB  - BACKGROUND: Breast cancer is the most common cancer affecting women in the UK.
      Tamoxifen (TAM) is considered as the standard of care for many women with
      oestrogen receptor positive breast cancer. However, wide variability in the
      response of individuals to drugs at the same doses may occur, which may be a
      result of interindividual genetic differences (pharmacogenetics). TAM is known to
      be metabolised to its active metabolites N-desmethyl TAM and 4-hydroxytamoxifen
      by a number of CYP450 enzymes, including CYP2D6, CYP3A4, CYP2C9, CYP2C19 and
      CYP2B6. N-desmethyl TAM is further metabolised to endoxifen by CYP2D6. Endoxifen,
      which is also formed via the action of CYP2D6, is 30- to 100-fold more potent
      than TAM in suppressing oestrogen-dependent cell proliferation, and is considered
      an entity responsible for significant pharmacological effects of TAM. Thus, an
      association between the cytochrome P450 2D6 (CYP2D6) genotype and phenotype
      (expected drug effects) is believed to exist and it has been postulated that
      CYP2D6 testing may play a role in optimising an individual's adjuvant hormonal
      treatment. OBJECTIVES: To determine whether or not testing for cytochrome P450
      2D6 (CYP2D6) polymorphisms in women with early hormone receptor positive breast
      cancer leads to improvement in outcomes, is useful for health decision-making and
      is a cost-effective use of health-care resources. DATA SOURCES: Relevant
      electronic databases and websites including MEDLINE, EMBASE and HuGENet? [Centers
      for Disease Control and Prevention (Office of Public Health Genomics), Human
      Genome Epidemiology Network] were searched until July 2009. Further studies that
      became known to the authors via relevant conferences or e-mail alerts from an
      automatically updated search of the Scopus database were also included as the
      review progressed, up to March 2010. REVIEW METHODS: A systematic review of the
      clinical effectiveness and cost-effectiveness of CYP2D6 testing was undertaken.
      As it was not possible to conduct meta-analyses, data were extracted into
      structured tables and narratively discussed. An exploratory analysis of
      sensitivity and specificity was undertaken. A review of economic evaluations and
      models of CYP2D6 testing for patients treated with TAM was also carried out.
      RESULTS: A total of 25 cohorts were identified which examined clinical efficacy
      (overall survival and relapse/recurrence), adverse events and endoxifen plasma
      concentrations by genotype/phenotype. Significantly, six cohorts suggest
      extensive metabolisers (Ems) appear to have better outcomes than either poor
      metabolisers (PMs) or PMs + intermediate metabolisers in terms of
      relapse/recurrence; however, three cohorts report apparently poorer outcomes for
      EMs (albeit not statistically significant). There was heterogeneity across the
      studies in terms of the patient population, alleles tested and outcomes used and
      defined. One decision model proposing a strategy for CYP2D6 testing for TAM was
      identified, but this was not suitable for developing a model to examine the cost
      effectiveness of CYP2D6 testing. It was not possible to produce a de novo model
      because of a lack of data to populate it. CONCLUSION: This is a relatively new
      area of research that is evolving rapidly and, although international consortia
      are collaborating, the data are limited and conflicting. Therefore, it is not
      possible to recommend pharmacogenetic testing in this patient population. Future
      research needs to focus on which alleles (including, or in addition to, those
      related to CYP2D6) reflect patient response, the link between endoxifen levels
      and clinical outcomes, and the appropriate pathways for implementation of such
      pharmacogenetic testing in patient care pathways.

PMID- 21906463
TI  - [A study on the construction, expression and immunosterility of Lagurus laguru
      zona pellucida 3 DNA vaccine pVAX1-sig-LTB-lZP3-C3d3].
AB  - AIM: To enhance the immunocontraceptive effect of Lagurus lagurus zona pellucida
      3 DNA vaccine, and to achieve the prospect of application through the pVAX1-sig
      LTB-lZP3-C3d3 different immunity pathway. METHODS: Two adjuvant molecules were
      constructed into the recombinant plasmid pVAX1-sig-LTB-lZP3-C3d3 as DNA vaccine
      which contains Escherichia coli heat-labile enterotoxin B subunit and the
      molecular adjuvant 3 copies of C3d. The results of RT-PCR and western blot showed
      that the DNA vaccine was expressed in mRNA and protein level. The female C57BL/6
      mice were immunized by three ways: intramuscular injection, intranasal or oral
      route.Antibody levels and types were detected by ELISA. RESULTS: ELISA results
      showed that recombinant plasmid pVAX1-sig-LTB-lZP3-C3d3 immunization induced
      specific IgG, IgA levels were significantly different comparing with control
      (P<0.01). Antifertility experiment showed that the experimental group reduced the
      average fertility significantly different compared with the control group
      (P<0.01). CONCLUSION: Restriction analysis, RT-PCR and Western blot showed that
      the recombinant plasmid constructed correctly and can be the expression of mRNA
      and protein levels.It resulted that the recombinant plasmid pVAX1-sig-LTB-lZP3
      C3d3 can induce the specific immune response efficiently and enhance the
      immunocontraceptive effects.

PMID- 21906464
TI  - [TLR4 expression of human PBMC treated by BCG and its role of immune activation].
AB  - AIM: To investigate TLR4 expression of human peripheral blood mononuclear cells
      (hPBMC) treated with BCG and its role of immune activation. METHODS: hPBMC were
      treated with BCG in vitro. TLR4 expression were detected by flow cytometry, IFN
      gamma and TNF-alpha expression of hPBMC in both BCG stimulated group and the
      control group were detected by ELISA. RESULTS: The expression of TLR4 in hPBMC
      treated with BCG was stronger than the control group significantly (P<0.01) and
      increased with the time. In 72 h the TLR4 expression of BCG group was (44.73 +/-
      0.0066)%, while the control group was (1.02 +/- 0.0024)%. BCG can promote hPBMC
      proliferation, and this enhancement was time-dependent. In 24 h, 48 h and 72 h
      IFN-gamma and TNF-alpha expression of BCG group were significantly higher than
      the control group(P<0.05), and this enhancement was time-dependent. CONCLUSION:
      BCG can on enhance TLR4 expression and promote immune activation of hPBMC.

PMID- 21906465
TI  - [Differences between CD3+ TCRvalpha24+ NKT cell and CD3+ TCRvbeta11+ NKT cell in
      PBMC].
AB  - AIM: Clarified the differences between CD3(+);TCRvalpha24(+); NKT cells and
      CD3(+);TCRvbeta11(+); NKT cells in their frequencies, subpopulations, phenotypes
      and biological functions, so as to fully understand the effects of NKT cells in
      immune responses. METHODS: PBMCs from blood donors were isolated and cell surface
      markers (CD3, TCRvalpha24, TCRvbeta11, CD4, CD8, CD45RA, CD62L, CCR7) and
      intracellular cytokines (IL-4, IFN-gamma) were detected by flow cytometry
      directly or after stimulation with PMA plus Ionomycin. RESULTS: The mean
      frequencies of CD3(+);TCRvalpha24(+); NKT cells and CD3(+);TCRvbeta11(+); NKT
      cells in PBMCs were 0.63% and 0.43% and they varied according to individuals. A
      small population of NKT cells coexpressed TCRvalpha24 and TCRvbeta11. The
      subpopulations of CD4(+); NKT 64.35%, CD8(+); NKT 19.04%, CD4(-);CD8(-); NKT
      17.18% in human CD3(+);TCRvalpha24(+); NKT cells and CD4(+); NKT 53.69%, CD8(+);
      NKT 18.99%, CD4(-);CD8(-); NKT 29.74% in CD3(+);TCRvbeta11(+); NKT cells could be
      identified based upon the expressions of CD4 and CD8 molecules. There were no
      significant differences between relative subtypes. The frequency of
      CD45RA(+);CD3(+);TCRvbeta11(+); NKT cells(71.14%) was higher than the frequency
      of CD45RA(+);CD3(+);TCRvalpha24(+); NKT cells and the differences between them
      were significant. The differences between the frequencies of
      CD62L(+);CD3(+);TCRvalpha24(+); NKT cells(46.26%) and
      CD62L(+);CD3(+);TCRvbeta11(+); NKT cells(42.36%), the frequencies of
      CCR7(+);CD3(+);TCRvalpha24(+); NKT cells(9.24%) and CCR7(+);CD3(+);TCRvbeta11(+);
      NKT cells(8.22%) were not significant. There were no significant differences in
      the secretions of IL-4 by CD3(+);TCRvalpha24(+); NKT cells(13.01%) and
      CD3(+);TCRvbeta11(+); NKT cells(6.62%), and IFN-gamma by CD3(+);TCRvalpha24(+);
      NKT cells(38.12%) and CD3(+);TCRvbeta11(+); NKT cells(26.95%). However, there
      were significant differences between the mean frequency of IFN-gamma(+);IL
      4(+);CD3(+);TCRvalpha24(+); NKT cells(12.65%) and that of IFN-gamma(+);IL
      4(+);CD3(+);TCRvbeta11(+); NKT cells(3.02%). CONCLUSION: There were some
      differences between CD3(+);TCRvalpha24(+); NKT cells and CD3(+);TCRvbeta11(+);
      NKT cells in their frequencies, phenotypes and productions of cytokines. In all,
      although their frequencies were low, the complicated phenotypes and high
      secretions of cytokines(IL-4 and IFN-gamma) assigned NKT cells immunoregulatory
      effects.

PMID- 21906466
TI  - [Induction of proinflammatory cytokines and cell apoptosis by Chlamydia
      pneumoniae Cpn0810].
AB  - AIM: To expresse the Chlamydia pneumoniae Cpn0810 in E.coli BL21, and to study
      weather could it inducing proinflamatory cytokines including TNF-alpha and IL-6
      in human monocytic (THP-1) and cell apoptosis. METHODS: Polymerase chain
      reaction(PCR) was used to amplify the Cpn0810 gene, PCR products were purified
      and cloned into the prokaryotic expression vector pGEX6p-2. The restriction
      plasmids pGEX6p-2/Cpn0810 confirmed by PCR and sequencing was transformed into
      E.coli BL21. The recombinant protein was purified with glutathione S-transferase
      (GST) resin chromatography of Novagen after renaturation. THP-1 cells were
      stimulated by different concentrations of Cpn0810 and for various durations to
      test the production and the expression of TNF-alpha and IL-6 by ELISA. Cell
      apoptosis was detected in C.pneumoniae Cpn0810 cells by Hoechst33258 fluorescence
      staining and Cell apoptosis was detected in THP-1 cells by Annexin-V-FITC
      propidiu-m iodide (PI) staining. RESULTS: The restriction enzymes cleavage
      analysis and nucleotide sequencing showed the target gene was successfully
      inserted into pGEX6p-2 prokaryotic expression vector. Cpn0810 stimulated THP-1
      cell to produce proinflamatory cytokines including TNF-alpha and IL-6 in a dose
      and time-dependent manner. After THP-1 cells were treated with 10 mg/L Cpn0810
      for 24 h, apoptosis with nuclear chromatin fragmentation as well as cell
      shrinkage was observed by fluorescent staining and microscopy; apoptosis of cell
      was detected after 24 h in THP-1 cells treated with Cpn0810. CONCLUSION: Cpn0810
      recombinant protein could stimulate THP-1 cell to produce and express
      proinflamatory cytokines including TNF-alpha and IL-6; After THP-1 cells were
      treated with 10 mg/L Cpn0810 for 24 h, apoptosis of cell was detected after 24 h
      in THP-1 cells treated with Cpn0810.

PMID- 21906467
TI  - [Effect of curcumin on IL-17-induced nitric oxide production and expression of
      iNOS in human keratinocytes].
AB  - AIM: To investigate the effect of curcumin on IL-17-induced NO production, mRNA
      and protein expression of iNOS in human keratinocyte cell lines(HaCaT cells).
      METHODS: HaCaT cells were stimulated with IL-17 and incubated with three doses of
      curcumin for 24h in vitro. After collections of supernatant, total RNA and
      protein, NO levels in supernatant were detected and fluorescence quantitative PCR
      and Western blot were performed to determine the effect of curcumin on NO levels
      and iNOS. RESULTS: IL-17 increased NO levels, and expression of iNOS in HaCaT
      cells(P<0.01). Curcumin decreased IL-17 induced NO production and the iNOS
      expression at mRNA (P<0.01) and protein (P<0.01) levels significantly.
      CONCLUSION: Curcumin down-regulates IL-17-induced NO secretions and iNOS
      expression in HaCaT cells, thus provides a theoretical basis for the treatment of
      inflammatory diseases of skin related to keratinocytes.

PMID- 21906469
TI  - [Construction of Trim6 eukaryotic expression vector and its expression in HEK293
      cells].
AB  - AIM: To construct the recombinant eukaryotic expression vector pcDNA3.1 (+)
      Trim6, and observe its expression in HEK293T cells in vitro. METHODS: The total
      RNA was isolated from HeLa cells. After amplification with reverse transcription
      polymerase chain reaction (RT-PCR), the target sequences were cloned into the
      pcDNA3.1(+). The recombinant vector was confirmed by restriction enzyme
      digestion, PCR and sequencing. Then it was transfected into HEK293T cells.After
      24 hours, the Trim6 expression was detected by Western blot. RESULTS: The results
      of the restriction enzyme digestion, PCR and sequencing confirmed the vector was
      constructed successfully, and it can express Trim6 protein in HEK293T cells.
      CONCLUSION: The vector is constructed successfully, which establishes the
      foundation for future research on the effect of Trim6.

PMID- 21906468
TI  - [Influence of angiotensin-(1-7) on angiotensin II induced rat's tubular
      epithelial-myofibroblast transdifferentiation].
AB  - AIM: To explore the influence of angiotensin-(1-7)[Ang-(1-7)] on angiotension
      II(Ang II) induced rat's tubular epithelial-myofibroblast transdifferentiation
      and the secretion of extracellular matrix. METHODS: The NRK52E were maintained
      and sub-cultured treated with Ang-(1-7) (10(-6); mmol/L) and Ang II(10(-6);
      mmol/L) for 24, 48, 72, 96 hours, we detect the protein expressions of E-cadherin
      and alpha-SMA by immunocytochemistry method; The content of Col I and FN in the
      cultured supernatant were measured by ELISA; The mRNA expression of E-cadherin,
      alpha-SMA, Col I and FN was detected by real-time PCR. RESULTS: Treat with ang II
      96 h, the protein and mRNA expression of E-cadherin decreased significantly
      (P<0.05), but the protein and mRNA expression alpha-SMA, col I and FN increased
      significantly (P<0.05); treat with Ang II and Ang-(1-7), the protein and mRNA
      expression of E-cadherin increased significantly (P<0.05), but the protein and
      mRNA expression alpha-SMA, col I and FN decreased significantly (P<0.05).
      CONCLUSION: Ang-(1-7) can inhibits Ang II-induced rat's tubular epithelial
      myofibroblast transdifferentiation and decrease the secretion of FN and Col I.

PMID- 21906470
TI  - [Synthesis and identification of the hapten and complete antigens for
      Zearalenone].
AB  - AIM: To synthesize and identify the hapten and complete antigens for Zearalenone
      for the purpose of preparation of anti-Zearalenone antibodies. METHODS:
      Zearalenone and carboxymethoxylamine hemihydrochloride were incubated to
      synthesize the hapten ZEN-oxime. The ZEN-oxime was identified by thin layer
      chromatography (TLC), high performance liquid chromatographic (HPLC) and liquid
      chromatography-tandem mass spectrometry (LC-MSn). The ZEN-oxime was further
      conjugated to bovine serum albumin (BSA) or ovalbumin (OVA) to form the complete
      antigens by NHS ester method. The complete antigens were identified by
      ultraviolet spectrum, 2, 4, 6-trinitrobenzene sulfonicacid method (TNBS) and
      immunological analysis. RESULTS: The results indicated that the hapten and
      complete antigens were prepared successfully. CONCLUSION: The hapten and complete
      antigens for Zearalenone have been successfully synthesized and identified by
      several methods, which enables further preparation of anti-Zearalenone
      antibodies.

PMID- 21906471
TI  - [Screening of single-chain variable fragment (scFv) to bone sialoprotein].
AB  - AIM: To select single-chain variable fragment(scFv) antibody specific for bone
      sialoprotein(BSP) from Human Single Fold scFv Libraries. METHODS: Human Single
      Fold scFv Libraries were panned against immobilized BSP in a microtiter plate,
      after three rounds of panning, 96 clones were determined specific to BSP. The
      specificity of each scFv clone was determined by ELISA. The coding gene for BSP
      protein scFv has been sequenced. RESULTS: Phage antibody for BSP protein had a
      specific combination character. There were 368 bp, 527 bp, 935 bp which werer
      light chain, heavy chain and joint gene fragment with the resuLt of PCR. The DNA
      sequence data showed that there were 11 differences of the amino acids in the
      light chain, while there were only 3 differences in the heavy chain of scFv.
      CONCLUSION: scFv specific to BSP has been identified by means of phage display
      technology.

PMID- 21906472
TI  - [Preparation and identification of OmpW monoclonal antibodies].
AB  - AIM: To prepare and characterize the mouse monoclonal antibodies against Vibrio
      parahaemolyticus OmpW. METHODS: The OmpW amino acid sequence from three diseased
      Vibrio was analyzed by Bioinformatics. Mice were immunized with r-OmpW which was
      highly expressed and purified in E.coli. Five Vibrio(Va, Vp, Vh, Vv, Van) were
      chosen as antigen for mAb selection.The characters of the anti-OmpW monoclonal
      antibodies were studied by Western blot, Flow Cytometry, indirect
      immunofluorescence. RESULTS: OmpW was testified a highly conservative membrane
      protein.Three clones of anti-OmpW mAb was obtained. The Ig subclass of the mAb
      secreted from fused cell S5C10 was IgG3, which of the titer was 4.6*10(4);. The
      mAb could specifically recognize Vibrio parahaemolyticus, Vibrio alginolyticus,
      Vibrio harveyi, Vibrio anguillarum, Vibrio vulnificus, which could not react with
      Pseudomonas flurosecens, Aeromonas hydrophila, Aeromonas sobria, Aeromonas
      hydrophila, Escherichia coli. CONCLUSION: The mAb could specially recognize five
      diseased Vibrio, which is a useful tool for the further study of the diagnosis of
      Vibrio.

PMID- 21906473
TI  - [Preparation and identification of monoclonal antibodies against Pla protein of
      Yersinia pestis].
AB  - AIM: To prepare the monoclonal antibody of Pla with recombinant Pla (rPla) by
      hybridoma cell technology, which will lay the foundation for related research
      work. METHODS: Purified rPla was collected by washing repeatedly with urea, and
      BALB/c mice were immunized by them. Hybridoma cells were achieved by Sp2/0 cell
      fusion with mouse spleen cells from successfully immunized mice. Monoclonal
      antibody was screened by indirect ELISA and Western blots with rPla, natural
      crude Pla and GST respectively. RESULTS: Three strains of hybridoma cells (named
      15B8, 14H4 and 19A4 respectively) which secreted stably the monoclonal antibody
      of Pla were obtained. Their subclasses were IgG2a and IgG1 in heavy chains and
      kappa chains in light chains. The ELISA titers of ascites were 10(6);
      respectively.Three of monoclonal antibody can react with natural crude Pla tested
      by western blots. CONCLUSION: Monoclonal antibody of natural Pla of Yersinia
      pestis were successfully got, which has laid the foundation for further study of
      the Pla protein and development diagnosis reagent.

PMID- 21906474
TI  - [Preparation and application of polyclonal antibody against mouse IL-1alpha].
AB  - AIM: To construct a recombinant plasmid encoding mouse IL-1alpha (mIL-1alpha),
      express and purify mIL-1alpha protein, and prepare its polyclonal antibody.
      METHODS: The cDNAs were obtained from the spleen cells of BALB/c mice and the
      full length of mIL-1alpha gene was amplified by RT-PCR. Then the mIL-1alpha gene
      was inserted into a prokaryotic expression vector pET32a(+) and the resulting
      recombinant plasmid was transformed into E.coli BL21(DE3). After auto-induction,
      the mIL-1alpha protein was expressed and purified by electro-elution. An anti-mIL
      1alpha polyclonal antibody was raised in New Zealand rabbits after immunization
      with the purified mIL-1alpha and the titer was determined by ELISA. The
      specificity of the polyclonal antibody was identified by Western blot and flow
      cytometry. RESULTS: The recombinant prokaryotic expression vector pET32a(+)-IL
      1alpha was successfully constructed, and the mIL-1alpha protein was expressed and
      purified. ELISA showed the titer of the anti-mIL-1alpha serum was 1:25 600.
      Western blot and flow cytometry demonstrated the high specificity of the
      polyclonal antibody to IL-1alpha. CONCLUSION: The rabbit anti-mIL-1alpha
      polyclonal antibody with high titer and specificity has been prepared after
      immunization with the purified mIL-1alpha protein, facilitating further
      functional studies of IL-1alpha.

PMID- 21906475
TI  - [Preparation of anti-human 4-1BB monoclonal antibody and characterization of its
      biological activities].
AB  - AIM: To prepare an anti-human 4-1BB functional monoclonal antibody and to
      characterize its biological activities. METHODS: A stable human 4-1BB molecule
      transfected cell line 293T/4-1BB was used as an antigen to immunize BALB/c mice.
      By means of the cell fusion by hybridoma technique and multiple cell subcloning
      and repeated screening with 293T/4-1BB as the antibody screening positive cell
      while 293T/mock as the negative cell. The hybridoma cell lines specifically
      secreting anti-4-1BB monoclonal antibodies were selected. Then their
      characteristics and its biological activities were investigated by Western blot,
      fast-strip routine Ig subclass typing method, indirect immunofluorescence,
      competitive inhibition test, (3);H-TdR and cell apoptosis analysis. RESULTS:
      Three hybridoma cell lines 1G5, 4B11 and 9F11 with the property of secreting
      specific anti-4-1BB monoclonal antibody continuously and steadily were
      successfully obtained. These monoclonal antibodies could bind to human 4-1BB
      epitopes on activated T cells and monocytoes and DC. Additionally, mAb 4B11 could
      promote T proliferation and enhance the growth and maturation of Mo-DC.
      CONCLUSION: Three hybridoma cell lines which secrete anti-4-1BB monoclonal
      antibodies steadily have been established. These monoclonal antibodies could
      specifically recognize 4-1BB molecule and mAb 4B11 had a potent function to
      promote T proliferation cell as well as to enhance the growth and maturation of
      Mo-DC in vitro.

PMID- 21906477
TI  - [The clinical significance of S100beta protein in cerebrospinal fluid and serum
      from the patients with cerebral hemorrhage].
AB  - AIM: To observe the change and the clinical significance of S100beta protein
      level in cerebrospinal fluid and serum from the patients with cerebral hemorrhage
      (CH). METHODS: ELISA was used to detect the expression of S100beta protein in CSF
      and serum from CH patients control with Inguinal Hernia or great saphenous varix
      patients. Meanwhile, rabbit CH model at 6 h, 12 h, 24 h, 48 h, 72 h and 96 h .
      RESULTS: The levels of CSF S100beta protein at acute stage of CH patients
      increased significantly compared with those at recovery stage of CH patients and
      control group(P<0.01). The levels of S100beta protein in CSF from CH patients
      increased significantly compared with those in serum (P<0.01).The levels of
      S100beta protein in CSF of rabbit experimental group increased significantly
      compared with those of sham operation group at different time points(P<0.01).
      CONCLUSION: The level of S100beta protein in CSF from CH patients increases. It
      may be a biomarker as reflecting degree of pathogenetic and predicting outcome in
      the CH patients.

PMID- 21906476
TI  - [The effects of VEGF-R inhibitor on podocytopathy of rats with type I diabetic
      nephropathy].
AB  - AIM: To explore the effect of VEGF inhibitor SU5416 on podocytopathy of rats with
      type I diabetic nephropathy. METHODS: Thirty male SD rats were randomly divided
      into three groups: normal control group(NC), diabetic nephropathy group(DN) and
      diabetic nephropathy treated with SU5416 group(SU5416). Rats with DN were induced
      by STZ. At the end of 8 weeks after SU5416 treatment, body weight (BW), kidney
      weight (KW), 24 h urine albuminuria excretion rate(24 h UAER), plasma glucose and
      creatinine were detected respectively. Renal morphology were stained with
      periodic acid-Schiff (PAS). And the expression of podocyte-specific genes nephrin
      and podocin were detected by immunofluorescence. The mRNA levels of genes and
      VEGF were assessed by real time-PCR respectively. RESULTS: Compared with NC
      group, DN rats'BW were decreased but the KW were increased, and the levels of
      blood glucose, creatinine, 24 h UAER and kidney cortex VEGF mRNA were
      significantly higher. The expression of nephrin and podocin were
      decreased(P<0.05), and GBM thickening and mesangial matrix expansion were
      developed. Treatment with SU5416 leads to a marked decrease of KW and the level
      of 24 h UAER. Concurrently, the expressions of nephrin and podocin were revert
      partly in response to SU5416(P<0.05), and pathological changes were successfully
      ameliorated. However, the KW, glucose, creatinine and the level of VEGF mRNA were
      not significantly affected by SU5416 treatment(P>0.05). CONCLUSION: VEGF-R
      inhibitor SU5416 can obviously ameliorate albuminuria and histologic changes, and
      restore the expression of podocyte-specific genes nephrin and podocin in DN rats,
      suggesting that VEGF-R inhibitor is beneficial for the repair of podocytes in DN,
      which might be an important adjunct for podocytopathy therapy.

PMID- 21906478
TI  - [Screening the serum protein biomarker of patients with sepsis by cytokine
      antibody chips].
AB  - AIM: To investigate the expression of inflammatory cytokines in patients with
      sepsis by cytokine antibody chips. METHODS: To screen the protein biomarker for
      rapidly diagnosing sepsis, 79 cytokines in 9 cases of patients with sepsis and 4
      cases of healthy control were measured using cytokine antibody chip. Analyse the
      signaling values of these 79 cytokines using SAM (significance analysis of
      microarray, SAM) software. RESULTS: By SAM analysis: insulin like growth factor
      binding protein-1 (IGFBP-1), epidermal growth factor (HGF), osteopotin, insulin
      like growth factor binding protein-4 (IGFBP-4), interferon inducible protein-10
      (IP-10) and B-lymphocyte chemoattractant (BLC) were identified to be highly
      expressed in the sepsis while platelet-derived growth factor-BB (PDGF-BB), brain
      derived neurotrophic (BDNF), macrophage inflammatory protein-1beta (MIP-1beta),
      interleukin-8 (IL-8), epidermal growth factor (EGF) and interleukin-1beta(IL
      1beta)lowly expressed. Cluster analysis of significantly expressed cytokines
      showed that the sepsis and the control formed distinctly separate groups.
      CONCLUSION: Antibody chips demonstrate a significant change in sepsis patients,
      screening the protein biomarker for rapidly diagnosing sepsis is feasible.

PMID- 21906479
TI  - Bioequivalence of topical clotrimazole formulations: an improved tape stripping
      method.
AB  - PURPOSE: Investigations were carried out to assess the use of tape stripping (TS)
      for the determination of bioequivalence of topical products containing 1%
      clotrimazole. METHODS: The study design involved the establishment of an
      appropriate application time, which was determined by conducting a dose duration
      study. Subsequently, two bioequivalence studies were conducted: i) using the
      brand (Canesten Topical - 1% clotrimazole cream) as both the test and the
      reference product and ii) comparing Canesten cream with a gel product containing
      the same concentration of clotrimazole (1%). Each tape strip was individually
      analyzed for clotrimazole content using an HPLC method and Transepidermal Water
      Loss (TEWL) measurements were used to normalize the stratum corneum thicknesses
      between subjects. RESULTS: The results of the TS investigations showed that, if
      the study is sufficiently powered, tape stripping may be used to determine
      bioequivalence according to the conventional bioequivalence limits of 0.8-1.25,
      as well as detect formulation differences between different clotrimazole
      products. CONCLUSIONS: The data from this study provided compelling evidence that
      tape stripping has the necessary attributes and potential to be used as a tool
      for the bioequivalence assessment of topical clotrimazole and/or other topical
      formulations, thereby circumventing the need to undertake expensive and time
      consuming clinical trials for such products. This article is open to POST
      PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by
      clicking on ABSTRACT on the issue's contents page.

PMID- 21906481
TI  - Kabuki syndrome: a new case associated with Becker nevus.
AB  - Kabuki syndrome or Kabuki makeup syndrome was first described in 1981 in Japan by
      two different groups of authors. These investigators described a group of
      patients sharing typical facial features, skeletal anomalies, mental retardation,
      short stature, and dermatoglyphic anomalies. The term Kabuki makeup syndrome was
      coined because the peculiar facial features of the patients were reminiscent of
      the Japanese Kabuki theater masks. In 1988, Niikawa et al, after studying 62
      patients, proposed five diagnostic criteria for this disease: peculiar facies (in
      100% of all patients), skeletal anomalies (92%), dermatoglyphic anomalies (93%),
      medium to moderate mental retardation (92%), and short stature (83% of all
      cases). In addition to these findings, a variety of anomalies have been
      associated with this syndrome - the most serious being cardiac, renal, and
      urogenital abnormalities. We present a case of Kabuki syndrome in a 6-year-old
      boy who, in addition to the various features typical of the disease, also
      exhibited a Becker nevus - a condition not previously associated with this
      syndrome. The usefulness of dermoscopy in studying alterations in the
      dermatoglyphic patterns is also discussed.

PMID- 21906480
TI  - Application of 12S rRNA gene for the identification of animal-derived drugs.
AB  - PURPOSE. Animal-derived drugs are the major source of biological products and
      traditional medicine, but they are often difficult to identify, causing confusion
      in the clinical application. Among these medicinal animals, a number of animal
      species are endangered, leading to the destruction of biodiversity. The
      identification of animal-derived drugs and their alternatives would be a first
      step toward biodiversity conservation and safe medication. Until now, no
      effective method for identifying animal-derived drugs has been demonstrated; DNA
      based species identification presents a brand-new technique. METHODS. We designed
      primers to amplify a 523-bp fragment of 12S rRNA and generated sequences for 13
      individuals within six medicinal animal species. We examined the efficiency of
      species recognition based on this sequence, and we also tested the taxonomic
      affiliations against the GenBank database. RESULTS. All the tested drugs were
      identified successfully, and a visible gap was found between the inter-specific
      and intra-specific variation. We further demonstrated the importance of data
      exploration in DNA-based species identification practice by examining the
      sequence characteristics of relative genera in GenBank. This region of the 12S
      rRNA gene had a 100% success rate of species recognition within the six medicinal
      animal species. CONCLUSIONS. We propose that the 12S rRNA locus might be
      universal for identifying animal-derived drugs and their adulterants. The
      development of 12S rRNA for indentifying animal-derived drugs that share a common
      gene target would contribute significantly to the clinical application of animal
      derived drugs and the conservation of medicinal animal species. This article is
      open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may
      comment by clicking on ABSTRACT on the issue's contents page.

PMID- 21906482
TI  - Digital dermatofibromas--common lesion, uncommon location: a series of 26 cases
      and review of the literature.
AB  - Dermatofibroma (DF), also referred to as cutaneous fibrous histiocytoma (CFH), is
      a common tumor of the skin presenting as a firm nodule located predominantly on
      the limbs and shoulder and pelvic girdles that often extends into superficial
      subcutaneous tissue. This is a retrospective study of 26 DFs located on digits.
      All case slides were retrieved from saved files for diagnostic verification. One
      case was rejected after revision of the diagnosis to giant cell tumor of the
      tendon sheath. The 26 remaining cases constitute this reported series. Digital
      DFs affected 27 to 70 year-olds in a 2.25:1 male to female ratio. The most common
      clinical diagnosis submitted was "growth" or wart. In only 6 out of the 26 cases
      was the pre-biopsy diagnosis of DF ventured. Although lesional tissue went to
      dermal margins in 14 specimens, only one has been re-excised in follow up ranging
      from 2 months to 10 years. Because DFs can resemble several entities including
      leiomyosarcoma and dermatofibrosarcoma protuberans, a lack of familiarity with
      the occurrence of DF on the digits may result in more aggressive treatment than
      otherwise necessary. DF should be in the differential diagnosis of circumscribed,
      firm nodules presenting on the digits.

PMID- 21906483
TI  - Dyschromatosis universalis hereditaria in an African American male.
AB  - Dyschromatosis universalis hereditaria (DUH) is a very rare genodermatosis
      characterized by generalized skin dyspigmentation. It is most common in Japan,
      but has also been reported in other parts of Asia, Europe, South America, and
      Africa. We report a case of a 44-year-old man born and raised in North America
      who presented with total skin discoloration since birth.

PMID- 21906484
TI  - [Atopic dermatitis, innate immunity, and infection].
AB  - The prevalence of atopic dermatitis is increasing in western societies and this
      disease has a significant effect on the quality of life of patients and their
      families. The pathophysiology is complex, but there are recent insights on innate
      and adaptive immunity dysfunction in this condition that increases the
      predisposition to colonization/infection with characteristic types of
      microorganisms. We provide an up-to-date review of the pathophysiology of atopic
      dermatitis, highlighting the clinical implications of skin barrier dysfunction
      and immunological deregulation. We suggest a useful approach for handling
      exacerbations and infectious events.

PMID- 21906485
TI  - Linear syringocystadenoma papilliferum: an uncommon event with a favorable
      prognosis.
AB  - Syringocystadenoma papilliferum (SCAP) is an uncommon cutaneous adnexal tumor of
      uncertain histogenesis. Various authors have postulated that the tumor
      differentiates toward apocrine gland, eccrine gland, or the apo-eccrine gland. We
      present a patient with an unusual linear form.

PMID- 21906486
TI  - Commentary on 'Degos disease: a C5b-9/interferon-alpha-mediated endotheliopathy
      syndrome' by Magro et al: a reconsideration of Degos disease as hematologic or
      endothelial genetic disease.
AB  - Magro et al in April of 2011 published a new article in the American Journal of
      Clinical Pathology on the etiology and treatment of Degos Disease (DD), and
      importantly, its fatal variant malignant atrophic papulosis (MAP). Specifically,
      Magro noted that MAP is a disease involving the complement cascade that can be
      treated effectively with eculizumab. DD has two variants, a benign variant
      confined to the skin and a malignant (heretofore fatal) variant that involves the
      skin and systemic organs. Five aspects of DD are discussed: (1) the clinical
      findings of DD, (2) thrombosis and DD, (3) the histology of DD, (4) the presence
      of viral like inclusions in the endothelial cells of patients with DD, and (5)
      the lack of any apparent immune defect that relates to DD. It seems the previous
      criteria for Degos Disease must be amended. Paroxysmal nocturnal hemoglobinuria
      (PNH) is discussed and its relationship with DD explored. Eculizumab has been
      approved to treat paroxysmal nocturnal hemoglobinuria. A review of the data
      suggests that MAP is a hematological or endothelial disease like PNH. PNH,
      eculizumab, and data about DD is discussed to give a basis for understanding DD
      and speculate why eculizumab may be promising for the treatment of MAP.

PMID- 21906487
TI  - Unknown: Multiple asymptomatic skin colored to yellowish papules over vulva.
AB  - Multiple syringomas of the vulva are an unusal finding. We report a 42-year-old
      woman with a 2 year history of asymptomatic yellow papules on the vulva that were
      proven to be syringomas by histopathologic examination.

PMID- 21906488
TI  - Genital primary herpes simplex infection in a 5-month-old infant.
AB  - Genital primary herpes simplex infection is very uncommon in infants.
      Asymptomatic and oral primary infections are the most frequent presentations in
      this age group. We report a case of genital primary herpetic infection in a 5
      month-old male, exclusively breastfed, whose mother suffered from active labial
      herpes.

PMID- 21906489
TI  - Phacomatosis pigmento-pigmentaria: aberrant dermal melanocytosis and nevus
      spilus.
AB  - We present a dermal melanocytosis with superimposed nevus spilus on the arm of a
      5-year-old boy. We recently introduced a new type of phacomatosis, which we
      termed "phacomatosis pigmentopigmentalis," that is analogous to phacomatosis
      pigmentokeratotica or pigmentovascularis, for describing the association of two
      pigmented nevi. The present case is an example of this type of phacomatosis,
      which now we prefer to define phacomatosis pigmento-pigmentaria according to the
      correct Latin terminology.

PMID- 21906490
TI  - [Scrotal ulcers revealing pulmonary and genitourinary tuberculosis].
AB  - A 76-year-old male patient with an angioimmunoblastic T-cell lymphoma under
      treatment with fludarabine was referred because of scrotal ulcers, evolving for
      several months. Respiratory, gastrointestinal, and urinary symptoms were denied.
      Histopathological examination showed the presence of a chronic inflammatory
      process with epithelioid granulomas. Ziehl-Neelsen stain was positive for acid
      fast bacilli. PCR analysis allowed the identification of a mycobacteria strain
      belonging to the Mycobaterium tuberculosis complex. Skin biopsy was repeated and
      culture revealed M. tuberculosis sensitive to traditional tuberculostatic drugs.
      This bacteria was also isolated in bronchial and urinary specimens. Although no
      abnormal findings were detected on chest radiography or abdominal
      ultrasonography, scrotal ultrasound showed areas of nodular thickening in the
      lower part of the epididymis. The diagnosis of cutaneous, lung, and genitourinary
      tuberculosis was made and the patient was treated with multidrug therapy
      (rifampicin 600 mg/day, isoniazid 250 mg/day, pyrazinamide 1500 mg/day, and
      ethambutol 1200 mg/day for the first 2 months, followed by rifampicin and
      isoniazid with the same dosages for the subsequent 7 months). Complete resolution
      of skin lesions was observed after two months of treatment. Diagnosis and
      treatment modalities are discussed. This case emphasizes the importance of
      considering tuberculosis in the differential diagnosis of genital ulcer.

PMID- 21906491
TI  - Practical tip: Chicago Sky Blue (CSB) stain can be added to the routine potassium
      hydroxide (KOH) wet-mount to provide a color contrast and facilitate the
      diagnosis of dermatomycoses.
AB  - Rapid confirmation of dermatomycoses is desirable because it allows the clinician
      to initiate appropriate therapy without delay. The routine potassium hydroxide
      (KOH) wet-mount is cheap and rapid to use but this method lacks a color contrast.
      We offer a simple practical tip of adding Chicago Sky Blue (CSB) stain to KOH to
      highlight fungal elements and provide a color contrast that makes reading and
      interpretation simple, even for the novice.

PMID- 21906492
TI  - Cutaneous melanoma in patients in treatment with biological therapy: review of
      the literature and case report.
AB  - Herein we report a case of a melanoma arising in a patient receiving adalimumab
      and methotrexate for rheumatoid arthritis. A limited number of studies reported
      melanoma growth in patients undergoing treatment with biologics. This case report
      with a brief review of literature suggests that patients under treatment with
      biologics should be counseled to identify new pigmented lesions or changes in
      preexisting nevi. Clinicians' collaboration will facilitate recognition and
      timely diagnosis of early melanoma. If there is any doubt, excision for
      histological evaluation should be considered. Pending new studies, careful
      observation is encouraged.

PMID- 21906493
TI  - Pigmented extramammary Paget disease of the abdomen: a potential mimicker of
      melanoma.
AB  - Extramammary Paget disease (EMPD) is a rare condition that usually presents in
      areas that are rich in apocrine sweat glands such as the vulva, scrotum, and
      perianal areas. The majority of these tumors represent cutaneous extension from a
      visceral adenocarcinoma, whereas a smaller proportion arise in the cutaneous
      apocrine glands themselves. Women in their sixth to eighth decades are most
      commonly affected. It is exceedingly rare for EMPD to present on the face, chest,
      or abdomen, and even more unusual for it to present as a pigmented lesion. We
      report the case of a 63-year-old woman with an underlying colon cancer who
      presented with a pigmented lesion in the midline of the abdomen above the
      umbilicus. Immunohistochemical stains demonstrated the lesion to be CK7+/CK20- as
      well as negative for melanocytic markers (S100, MiTF, Melan-A, HMB-45). Further,
      the immunophenotype of the EMPD differed from the patient's underlying colon
      adenocarcinoma (CK20+/CK7-), arguing against an ectopic focus of her established
      disease. Making the distinction between pigmented EMPD and melanoma is a
      potential diagnostic pitfall because of the histologic similarities. Extramammary
      Paget disease should be considered in the morphologic differential diagnosis of
      melanoma and, if necessary, supporting studies should performed to aid in this
      distinction.

PMID- 21906494
TI  - DRESS syndrome associated with raltegravir.
AB  - Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or drug
      induced hypersensitivity is a potentially life-threatening drug hypersensitivity
      syndrome most commonly associated with anticonvulsants, allopurinol, long-acting
      sulfonamides, dapsone, and minocycline. In the setting of HIV infection, the
      antiretroviral medicines abacavir, nevirapine, and efavirenz have all shown well
      documented associations with DRESS syndrome. There has only been one case (in a
      poster presentation) of this syndrome in a patient who was taking raltegravir.

PMID- 21906495
TI  - Salim Haim and the syndrome that bears his name.
AB  - Professor Salim Haim (1919-1983) was a well-known dermatologist. In 1965, Dr.
      Haim and Dr. Munk, a radiologist, reported a rare congenital type of
      genodermatosis, later known as Haim-Munk syndrome. This syndrome is characterized
      by palmoplantar keratosis, pes planus, onychogryphosis, periodontitis,
      arachnodactyly, and acroosteolysis. This report discusses Haim and Haim-Munk
      syndrome.

PMID- 21906496
TI  - Sexual assault and substance use in male veterans receiving a brief alcohol
      intervention.
AB  - OBJECTIVE: Many studies have documented the link between substance use and a
      history of sexual assault in women; however, few studies have examined this
      relationship in men. The purpose of this study was to explore the rates of sexual
      assault in a sample of male veterans reporting alcohol misuse and to further
      explore potential differences in alcohol use patterns and alcohol-related
      characteristics in those with and without a history of sexual assault. We also
      explored the types of illicit drugs being used in the past 90 days and whether a
      clinical sample of male veterans reporting sexual assault are at greater odds of
      using these substances when compared with their peers with no history of sexual
      assault. METHOD: Data were collected on a nationwide sample (N = 880) of male
      veterans receiving care in Veterans Administration outpatient mental health
      clinics. RESULTS: We found that 9.5% of our sample reported a history of sexual
      assault, and those with this history reported increased alcohol consumption, a
      greater number of alcohol-related consequences, and an increased likelihood of
      using an illicit substance in the past 90 days. The most commonly used illicit
      substances were cannabis, cocaine, and opiates. Those with sexual assault
      histories were also more likely to report risk factors that may exacerbate the
      negative effects of any level of alcohol consumption. CONCLUSIONS: Our findings
      highlight the burden of alcohol and illicit drug use among male veterans and
      suggest that substance use disorder treatment settings may be a context in which
      prevalence of a history of sexual assault is high. Our findings further support
      prior call for universal screening for sexual assault among this population.

PMID- 21906497
TI  - Association between adolescent drinking and adult violence: evidence from a
      longitudinal study of urban African Americans.
AB  - OBJECTIVE: This study examined the relationship between adolescent alcohol use
      and adult violence from a developmental perspective, specifically whether
      frequent adolescent drinking predicts adult violence once shared risk factors are
      taken into account through propensity score matching. The research considered
      multiple types of violence, including assault, robbery, and suicidal behavior, as
      well as other types of offending. It tested whether educational attainment and
      adult alcohol use and problems contribute to the adolescent drinking-adult
      violence relationship. METHOD: Data came from a longitudinal epidemiological
      study of a community cohort of urban African Americans followed from age 6 to 42
      (N = 702; 51% female). Frequent adolescent drinking was operationalized as 20
      times or more by age 16. Data on violent arrests and offenses were collected
      throughout adulthood from self-reports and official criminal records. Matching
      variables came from childhood and adolescence and included such shared risk
      factors as childhood externalizing behaviors, school achievement, and family
      functioning. RESULTS: Adjusted logistic regression analyses on the sample matched
      on childhood and adolescent risk factors showed that frequent adolescent drinking
      was associated with an increased risk of violence in young adulthood (in
      particular assault) but not with other types of crime, self-directed violence, or
      violence in midlife. Findings varied by gender. Heavy episodic drinking in
      adulthood seemed to account for some of the association between frequent
      adolescent drinking and adult assault. CONCLUSIONS: The results of this study
      suggest that preventing frequent adolescent drinking could potentially decrease
      adult assault. This study adds to the growing body of literature suggesting long
      term negative consequences of adolescent alcohol use.

PMID- 21906498
TI  - Parental problem drinking, marital aggression, and child emotional insecurity: a
      longitudinal investigation.
AB  - OBJECTIVE: Marital aggression plays an important role in relations between
      parental problem drinking and child maladjustment. The purpose of the current
      study was to apply emotional security theory as a framework for understanding the
      role of marital aggression. METHOD: A community sample of 235 children in
      kindergarten participated once a year for 3 years. Parents completed measures of
      parental problem drinking and marital aggression, and children were interviewed
      about their emotional security reactions to marital conflict vignettes. RESULTS:
      Greater parental problem drinking was directly associated with children's more
      negative emotional reactions to conflict. Maternal problem drinking predicted
      increased sad reactions and negative expectations for the future. Paternal
      problem drinking predicted increases in child anger reactions and negative
      expectations for the future. Parental problem drinking was also indirectly
      associated with child reactions via marital aggression. CONCLUSIONS: Results
      confirmed hypotheses that parental problem drinking would be related to child
      emotional insecurity and that associations would be indirect via greater marital
      conflict. Findings are interpreted in terms of emotional security theory as a
      framework for understanding the effects of parental problem drinking on marital
      aggression and child development.

PMID- 21906499
TI  - Alcohol and homicide in Russia and the United States: a comparative analysis.
AB  - OBJECTIVE: The object of this study was to perform a comparative analysis of the
      aggregate relationship between alcohol and homicide in Russia and in the United
      States. The comparison was based on the magnitude of the alcohol effect, the
      alcohol attributable fraction (AAF), and the degree to which total consumption
      could account for trends in homicide. METHOD: We analyzed total and sex-specific
      homicide rates for the age groups 15-64 years, 15-34 years, and 35-64 years. The
      study period was 1959-1998 for Russia and 1950-2002 for the United States. For
      the United States, alcohol consumption was gauged by sales of alcohol; for
      Russia, estimated unrecorded consumption was included as well. The data were
      analyzed through autoregressive integrated moving average (ARIMA) modeling.
      RESULTS: The results show that, for Russia as well as for the United States, a 1
      L increase in consumption was associated with an increase in homicides of about
      10%, although the absolute effect was markedly larger in Russia because of
      differences in homicide rates. The AAF estimates suggested that 73% and 57% of
      the homicides would be attributable to alcohol in Russia and in the United
      States, respectively. Most of the temporal variation in the Russian homicide rate
      could be accounted for by the trend in drinking, whereas the U.S. trend in total
      alcohol consumption had a more limited ability to predict the trend in homicides.
      CONCLUSIONS: We conclude that the role of alcohol in homicide seems to be larger
      in Russia than in the United States.

PMID- 21906500
TI  - Fire fatality and alcohol intake: analysis of key risk factors.
AB  - OBJECTIVE: After a brief review of the literature on the role of alcohol in
      residential fire deaths, a comparison of different risk factors for residential
      fire fatality was undertaken by closely analyzing the circumstances of fire
      victims as a function of alcohol intake. METHOD: Analyses were based on
      Australian coroners' fire fatality records for the state of Victoria (1998-2006)
      and considered demographic, behavioral, and environmental factors for the 95
      adult fire victims who were tested for alcohol (64 male, 31 female). RESULTS:
      Most (58%) had a positive blood alcohol concentration (BAC) test, with 31% of the
      total sample having a BAC of more than 0.20 gm per 100 ml. Odds ratio analyses
      showed that four variables were significantly more associated with victims who
      had consumed alcohol compared with sober victims. In descending odds ratio order,
      these variables were as follows: (a) being aged 18-60 years, (b) involving
      smoking materials (e.g. cigarettes, pipes), (c) having no conditions preventing
      escape, and (d) being male. An important new finding is that fire fatalities with
      positive BAC levels were more than three times less likely to have their clothing
      alight or exits blocked than sober fire victims. CONCLUSIONS: The risk of dying
      in a fire for alcohol-affected people who are capable of being alerted and
      escaping may be reduced if they can be alerted more quickly and effectively.
      Suitable measures for improving smoke alarms via interlinking and the use of an
      alarm signal demonstrated to be more effective at waking sleepers, including
      those who are alcohol affected, are discussed.

PMID- 21906501
TI  - Marked decline in 3,4-methylenedioxymethamphetamine (MDMA) based on wastewater
      analysis.
AB  - OBJECTIVE: Recent reports in Europe suggest a decline in 3,4
      methylenedioxymethamphetamine (MDMA; Ecstasy) use, but quantifiable and objective
      measurement is unavailable. The global extent of changes in MDMA and related
      stimulant use is also unclear. This study aims to quantify changes in MDMA use in
      Australia and determine whether these changes have been accompanied by differing
      amounts of other stimulant use. METHOD: We acquired information on recent use of
      MDMA and related illicit stimulants in Australia using the method of wastewater
      analysis. Untreated wastewater samples collected from three metropolitan
      treatment plants in Adelaide from May to July 2009 and the same months in 2010
      were analyzed. Concentrations of MDMA, methamphetamine, and benzoylecgonine (a
      metabolite of cocaine) were determined using solid phase extraction-liquid
      chromatography- tandem mass spectrometry. Weekly consumed doses of MDMA,
      methamphetamine, and cocaine per 1,000 people were estimated. RESULTS: From 2009
      to 2010, weekly consumption of MDMA decreased from mean of 4.52 (SEM = 0.74)
      doses/week per 1,000 people to 0.08 (0.01) doses/week per 1,000 people (p <
      .001); weekly consumption of methamphetamine increased from a mean of 48.35
      (6.13) doses/week per 1,000 people to 68.13 (5.33) doses/week per 1,000 people (p
      < .05); and weekly consumed doses of cocaine did not significantly change. Local
      roadside saliva testing data also showed that the MDMA-positive test rate
      decreased from 0.30% to 0.05% and the methamphetamine-positive test rate
      increased from 1.43% to 1.52% during the past 2 years. CONCLUSIONS: This study
      shows a 50-fold decrease in consumed doses of MDMA with a rise in methamphetamine
      use in Australia over a 1-year period.

PMID- 21906502
TI  - Childhood risk factors for early-onset drinking.
AB  - OBJECTIVE: There is relatively little research on the childhood antecedent
      predictors of early-onset alcohol use. This study examined an array of
      psychosocial variables assessed at age 10 and reflecting Problem Behavior Theory
      as potential antecedent risk factors for the initiation of alcohol use at age 14
      or younger. METHOD: A sample of 452 children (238 girls) ages 8 or 10 and their
      families was drawn from Allegheny County, PA, using targeted-age directory
      sampling and random-digit dialing procedures. Children and parents were
      interviewed using computer-assisted interviews. Logistic regression analyses were
      used to examine the age-10 univariate and multivariate predictors of the
      initiation of alcohol use by age 14 or younger. RESULTS: Twenty-five percent of
      the sample reported having more than a sip or a taste of alcohol in their life by
      age 14. Sex, race, and age cohort did not relate to early drinking status.
      Children with two parents were less likely to initiate drinking early. Early
      initiation of drinking related significantly to an array of antecedent risk
      factors (personality, social environment, and behavioral) assessed at age 10 that
      reflect psychosocial proneness for problem behavior. In the multivariate model,
      the variables most predictive of early-onset drinking were having a single
      parent, sipping or tasting alcohol by age 10, having parents who also started
      drinking at an early age, and parental drinking frequency. CONCLUSIONS:
      Initiation of alcohol use by age 14 reflects childhood psychosocial proneness to
      engage in problem behavior as measured by Problem Behavior Theory and having a
      family environment conducive to alcohol use.

PMID- 21906503
TI  - Different phenotypic and genotypic presentations in alcohol dependence: age at
      onset matters.
AB  - OBJECTIVE: Several theoretical typology models have been proposed to classify
      alcoholism into more homogeneous subtypes using various criteria, for which age
      at onset of alcohol dependence is shared across many models. We investigated the
      evidence for the distinction between early- versus late-onset alcoholism by
      examining relevant phenotypic and genotypic variables. METHOD: Data are from
      1,248 individuals with alcohol dependence, who were interviewed to collect
      detailed clinical information. Early versus late onset of alcohol dependence was
      defined by the age at onset of 22 years. Odds ratio (OR) and Cohen's d were
      calculated as effect size for comparisons of clinical features between the two
      groups. We adjusted interviewed age and gender in logistic regression models.
      Case-control genetic analyses were conducted for the association between HTR1B,
      SLC6A4, DRD2, and OPRMU1 genes and subgroups of alcohol dependence using a sample
      of 530 controls screened for alcohol problems. RESULTS: Early-onset alcoholism
      exhibited significantly (p < .01) different clinical characteristics from late
      onset alcoholism, including higher severity in alcohol dependence symptoms (d =
      0.22) and maximum drinking quantity within 24 hours (d = 0.40), more rapid
      progression from regular drinking to meet alcohol dependence diagnosis (d =
      1.73), higher expectancies for alcohol (d = 0.22-0.47), more comorbidity with
      externalizing disorders (ORs = 2.8-2.9), and greater prevalence of family alcohol
      use problems (d = 0.26-0.43). In addition, markers in the HTR1B and OPRMU1 genes
      showed genetic associations with subgroups of alcohol dependence (ORs = 1.5-2.4).
      CONCLUSIONS: Our findings support that subgroups of alcohol dependence defined by
      onset age have phenotypic and genetic differences. The early-onset subgroup had
      more severe features for almost every aspect we examined. Coupled with genetic
      association findings, age at onset of alcohol dependence may serve as a simple
      but important clinical marker with implications for future etiological research
      and intervention.

PMID- 21906504
TI  - Men's and women's pathways to adulthood and associated substance misuse.
AB  - OBJECTIVE: Social role transitions have been linked to changes in substance use
      and misuse during young adulthood. This study examined how commonly observed
      pathways to adulthood, defined by education, employment, marriage, and
      parenthood, were associated with alcohol, tobacco, and marijuana misuse from ages
      18 to 33. METHOD: Data came from a longitudinal panel of 412 men and 396 women
      recruited when they were in fifth grade in Seattle public schools in 1985.
      Participants were followed through age 33 in 2008, with 92% retention. RESULTS:
      Young adults who had little postsecondary education and remained unmarried
      through age 30 generally had the highest rates of substance misuse. Those who
      were involved in postsecondary education and postponed family formation had the
      lowest rates, particularly with respect to daily smoking and nicotine dependence.
      Parenting during the young adult years was associated with lower rates of
      substance misuse for both men and women. However, taking on parenting
      responsibilities early, during the late teen years and early 20s (observed mostly
      for women), was associated with higher rates of tobacco misuse. Differences in
      substance misuse by pathways to adulthood were fairly constant across the young
      adulthood years and were already observed at age 18, suggesting that substance
      misuse patterns are established early. CONCLUSIONS: Young adults may change their
      substance use only partially in response to new freedoms and responsibilities in
      young adulthood. Preventive efforts should include a focus on early initiation of
      substance use and educational experiences that move people into life trajectories
      and associated substance misuse patterns.

PMID- 21906505
TI  - Hospitalizations for alcohol and drug overdoses in young adults ages 18-24 in the
      United States, 1999-2008: results from the Nationwide Inpatient Sample.
AB  - OBJECTIVE: Recent reports indicate an increase in rates of hospitalizations for
      drug overdoses in the United States. The role of alcohol in hospitalizations for
      drug overdoses remains unclear. Excessive consumption of alcohol and drugs is
      prevalent in young adults ages 18-24. The present study explores rates and costs
      of inpatient hospital stays for alcohol overdoses, drug overdoses, and their co
      occurrence in young adults ages 18-24 and changes in these rates between 1999 and
      2008. METHOD: Data from the Nationwide Inpatient Sample were used to estimate
      numbers, rates, and costs of inpatient hospital stays stemming from alcohol
      overdoses (and their subcategories, alcohol poisonings and excessive consumption
      of alcohol), drug overdoses (and their subcategories, drug poisonings and
      nondependent abuse of drugs), and their co-occurrence in 18- to 24-year-olds.
      RESULTS: Hospitalization rates for alcohol overdoses alone increased 25% from
      1999 to 2008, reaching 29,412 cases in 2008 at a cost of $266 million.
      Hospitalization rates for drug overdoses alone increased 55%, totaling 113,907
      cases in 2008 at a cost of $737 million. Hospitalization rates for combined
      alcohol and drug overdoses increased 76%, with 29,202 cases in 2008 at a cost of
      $198 million. CONCLUSIONS: Rates of hospitalizations for alcohol overdoses, drug
      overdoses, and their combination all increased from 1999 to 2008 among 18- to 24
      year-olds. The cost of such hospitalizations now exceeds $1.2 billion annually.
      The steepest increase occurred among cases of combined alcohol and drug
      overdoses. Stronger efforts are needed to educate medical practitioners and the
      public about the risk of overdoses, particularly when alcohol is combined with
      other drugs.

PMID- 21906506
TI  - Psychosocial correlates of alcohol use and reduction for individuals with
      hepatitis C.
AB  - OBJECTIVE: Patients with hepatitis C virus (HCV) are advised to refrain from
      alcohol consumption. A questionnaire was developed to measure concepts associated
      with alcohol use for individuals with HCV. METHOD: Subjects with HCV (N = 527)
      completed a telephone survey. Eligible respondents had screened negative for
      current abuse/dependence disorders (Alcohol Use Disorders Identification Test
      [AUDIT] <= 10). Measures of personality, self-efficacy, knowledge, readiness,
      coping styles, stigma, and symptoms were examined for associations with alcohol
      use. RESULTS: Factor analysis supported a measurement structure of 105 items in
      35 subdomains. A total of 26 subdomains had significant bivariate associations
      with alcohol use. Higher self-efficacy for resisting drinking in social
      situations was associated with lower alcohol use (r = -.68, p < .001), as was
      knowledge of alcohol and HCV (r = -.27, p < .001). Although agreeableness and
      marital status are typically associated with lower current drinking in samples of
      those with alcohol use problems, in our study agreeableness (beta = .13, p < .01)
      and marital status (beta = .08, p < .05) were modestly associated with higher
      current drinking. The final multivariate R2 was .55. CONCLUSIONS: The pattern of
      associations suggests the importance of the social aspects of drinking for
      drinking decisions. Existing brief interventions will need to be tailored to a
      contextualized psychosocial model for medical patients with HCV and AUDIT scores
      <= 10 to optimize effectiveness. Such future interventions should emphasize the
      potential medical hazards of drinking for persons with HCV, the maintenance of
      social relationships in the absence of alcohol use, and strategies for building
      confidence for resisting drinking in specific situations.

PMID- 21906508
TI  - Psychometric performance of DSM-IV alcohol use disorders in young adulthood:
      evidence from an Australian general population sample.
AB  - OBJECTIVE: The current study investigates the performance of alcohol use
      disorders in young adults using item response theory and differential item
      functioning (DIF). METHOD: The 1997 National Survey of Mental Health and
      Wellbeing (Australia) sample was based on a stratified, multistage area
      probability sample of people ages 18 years and older in the Australian
      population. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition
      (DSM-IV), alcohol use disorders were assessed in all current alcohol users (N =
      7,746; 44.2% female). The psychometric properties of the DSM-IV alcohol use
      disorder criteria in young adults were assessed using item response theory. Age
      based DIF was also assessed in each of the DSM-IV criteria for alcohol use
      disorders. The presence of age-based DIF in subgroups defined by sex and
      consumption was also examined. RESULTS: Overall, problems were identified in the
      use in hazardous situations, persistent desire/inability to quit/cut down, and
      tolerance criteria in young adults. However, the DIF identified at the criterion
      level had little impact on total information provided by the criteria across the
      two age groups. Subgroup analyses indicated that for the female-only and non
      heavy using subgroups, DIF was no longer detected in the use in hazardous
      situations criterion. The alcohol use disorder criteria were found to provide
      maximum information about moderate to severe pathology among young adults. There
      was little evidence for the DSM-IV abuse/dependence distinction in young
      adulthood. CONCLUSIONS: Some of the DSM-IV alcohol use disorder criteria appear
      problematic when applied to young adults, and future research needs to focus on
      clarifying young adults' understanding of these problematic criteria. Although
      DIF was identified in three of the alcohol use disorder criteria, the total
      information provided by these criteria was largely the same among younger and
      older age groups.

PMID- 21906507
TI  - Racial/ethnic differences in the etiology of alcohol use among urban adolescents.
AB  - OBJECTIVE: We examined relations between neighborhood context, home and family
      management practices, deviant peer affiliations, beliefs favorable to use, and
      alcohol use among urban African American and Hispanic adolescents. METHOD: The
      sample comprised 4,027 African American and Hispanic adolescents who were 50%
      boys and 75% low income. Participants completed surveys in 2002-2005 and 2008
      2009. Structural equation modeling assessed direct and indirect relations between
      neighborhood context in 6th grade, home and family management practices in 7th
      grade, deviant peer affiliations and beliefs favorable to use in 8th grade, and
      alcohol use in 12th grade. RESULTS: There was significant variation in structural
      models across race/ethnicity but not gender. Differences included the influence
      of neighborhood and school strength and, where similarities existed, differences
      in effect magnitude. Similarities included significant correlations among
      measurement components; the indirect influence of alcohol advertisement exposure,
      gender, area deprivation, and home alcohol access on alcohol use; direct
      influence of deviant peer affiliations and beliefs favorable to use on alcohol
      use; and indirect effects highlighting the importance of preventing home alcohol
      access, deviant peer affiliations, and beliefs favorable to use and promoting
      protective family management practices. CONCLUSIONS: Neighborhood and school
      strength may be particularly important in preventing alcohol use among African
      Americans, whereas preventing early onset of alcohol use among Hispanics remains
      important. Preventive efforts may wish to focus on neighborhood deprivation,
      exposure to alcohol advertisements, and home risks and protective factors because
      they have direct and indirect effects on intrapersonal factors and alcohol use.

PMID- 21906509
TI  - Multisite cost analysis of a school-based voluntary alcohol and drug prevention
      program.
AB  - OBJECTIVE: This article estimates the societal costs of Project CHOICE, a
      voluntary after-school alcohol and other drug prevention program for adolescents.
      To our knowledge, this is the first cost analysis of an after-school program
      specifically focused on reducing alcohol and other drug use. METHOD: The article
      uses microcosting methods based on the societal perspective and includes a number
      of sensitivity analyses to assess how the results change with alternative
      assumptions. Cost data were obtained from surveys of participants, facilitators,
      and school administrators; insights from program staff members; program
      expenditures; school budgets; the Bureau of Labor Statistics; and the National
      Center for Education Statistics. RESULTS: From the societal perspective, the cost
      of implementing Project CHOICE in eight California schools ranged from $121 to
      $305 per participant (Mdn = $238). The major cost drivers included labor costs
      associated with facilitating Project CHOICE, opportunity costs of displaced class
      time (because of in-class promotions for Project CHOICE and consent obtainment),
      and other efforts to increase participation. Substituting nationally
      representative cost information for wages and space reduced the range to $100
      $206 (Mdn = $182), which is lower than the Substance Abuse and Mental Health
      Services Administration's estimate of $262 per pupil for the "average effective
      school-based program in 2002." Denominating national Project CHOICE costs by
      enrolled students instead of participants generates a median per-pupil cost of
      $21 (range: $14-$28). CONCLUSIONS: Estimating the societal costs of school-based
      prevention programs is crucial for efficiently allocating resources to reduce
      alcohol and other drug use. The large variation in Project CHOICE costs across
      schools highlights the importance of collecting program cost information from
      multiple sites.

PMID- 21906510
TI  - Descriptive drinking norms: For whom does reference group matter?
AB  - OBJECTIVE: Perceived descriptive drinking norms often differ from actual norms
      and are positively related to personal consumption. However, it is not clear how
      normative perceptions vary with specificity of the reference group. Are drinking
      norms more accurate and more closely related to drinking behavior as reference
      group specificity increases? Do these relationships vary as a function of
      participant demographics? The present study examined the relationship between
      perceived descriptive norms and drinking behavior by ethnicity (Asian or White),
      sex, and fraternity/sorority status. METHOD: Participants were 2,699 (58% female)
      White (75%) or Asian (25%) undergraduates from two universities who reported
      their own alcohol use and perceived descriptive norms for eight reference groups:
      "typical student"; same sex, ethnicity, or fraternity/sorority status; and all
      combinations of these three factors. RESULTS: Participants generally reported the
      highest perceived norms for the most distal reference group (typical student),
      with perceptions becoming more accurate as individuals' similarity to the
      reference group increased. Despite increased accuracy, participants perceived
      that all reference groups drank more than was actually the case. Across specific
      subgroups (fraternity/sorority members and men) different patterns emerged.
      Fraternity/sorority members reliably reported higher estimates of drinking for
      reference groups that included fraternity/ sorority status, and, to a lesser
      extent, men reported higher estimates for reference groups that included men.
      CONCLUSIONS: The results suggest that interventions targeting normative
      misperceptions may need to provide feedback based on participant demography or
      group membership. Although reference group-specific feedback may be important for
      some subgroups, typical student feedback provides the largest normative
      discrepancy for the majority of students.

PMID- 21906511
TI  - They drink how much and where? Normative perceptions by drinking contexts and
      their association to college students' alcohol consumption.
AB  - OBJECTIVE: Prior research has shown that normative perceptions of others'
      drinking behavior strongly relates to one's own drinking behavior. Most research
      examining the perceived drinking of others has generally focused on specificity
      of the normative referent (i.e., gender, ethnicity). The present study expands
      the research literature on social norms by examining normative perceptions by
      various drinking contexts. Specifically, this research aimed to determine if
      college students overestimate peer drinking by several drinking contexts (i.e.,
      bar, fraternity/sorority party, non-fraternity/sorority party, sporting event)
      and to examine whether normative perceptions for drinking by contexts relate to
      one's own drinking behavior specific to these contexts. METHOD: Students (N =
      1,468; 56.4% female) participated in a web-based survey by completing measures
      assessing drinking behavior and perceived descriptive drinking norms for various
      contexts. RESULTS: Findings demonstrated that students consistently overestimated
      the drinking behavior for the typical same-sex student in various drinking
      contexts, with the most prominent being fraternity/sorority parties. In addition,
      results indicated that same-sex normative perceptions for drinking by contexts
      were associated with personal drinking behavior within these contexts.
      CONCLUSIONS: Results stress the importance of specificity of social norms beyond
      those related to the normative referent. Clinical implications are discussed in
      terms of preventions and intervention efforts as well as risks associated with
      drinking in a novel context.

PMID- 21906512
TI  - Attachment avoidance and anxiety as predictors of 12-step group engagement.
AB  - OBJECTIVE: Twelve-step mutual help groups such as Alcoholics Anonymous (AA) rely
      heavily on social interactions and support to reduce drinking, but little is
      known about how individual differences in social behavior tendencies, such as
      adult attachment, affect 12-step group engagement and resulting benefits. This
      prospective study investigated relationships between the anxiety and avoidance
      dimensions of adult attachment and subsequent 12-step meeting attendance, program
      behaviors, sponsorship, and alcohol use. METHOD: Early 12-step group affiliates
      (N = 253) were recruited from community-based AA and from outpatient treatment.
      Participants completed baseline interviews that included the Relationship
      Questionnaire, measures of motivation and professional treatment, and measures of
      12-step meeting attendance, practices, and sponsorship. Follow-up interviews were
      conducted at 3, 6, 9, 12, 18, and 24 months. RESULTS: At baseline, participants
      reported elevated attachment anxiety relative to a college population. Lagged
      analyses demonstrated that, as predicted, high attachment avoidance was related
      to lower rates of 12-step meeting attendance, practice of behaviors prescribed by
      12-step organizations, and lower probability of acquiring a sponsor. Attachment
      anxiety did not predict any of these aspects of subsequent 12-step group
      engagement. Contrary to predictions, baseline attachment avoidance did not
      moderate the relationship between early sponsorship and alcohol use. CONCLUSIONS:
      Findings support the hypothesis that social demands of behaviors prescribed by 12
      step groups may deter high-avoidance individuals from fully engaging in them.
      Perhaps because of instability in attachment avoidance in this population,
      however, baseline attachment avoidance did not predict drinking outcomes or
      moderate sponsor benefits.

PMID- 21906513
TI  - Twelve-step program attendance and polysubstance use: interplay of alcohol and
      illicit drug use.
AB  - OBJECTIVE: The primary aim of this study was to advance understanding of the
      efficacy of 12-step programs by determining the temporal relationships between
      alcohol and illicit drug use among 12- step program affiliates. METHOD: A total
      of 253 early 12-step affiliates without extensive histories of Alcoholics
      Anonymous (AA) attendance were recruited from substance use treatment and
      community-based AA. A majority of the sample met criteria for a diagnosis of
      alcohol dependence, reported lifetime use of illicit drugs, and reported illicit
      drug use in the 90-day period before recruitment. After informed consent,
      participants were interviewed at intake and in 3-month increments for 1 year.
      RESULTS: Preliminary analyses indicated that 12-step attendance was predictive of
      reductions in substance use and that such reductions were not moderated by
      illicit substance use disorder diagnosis or alcohol problem severity. Lagged
      hierarchical linear models indicated that illicit drug use was a robust predictor
      of later use of alcohol, although the frequency and intensity of drinking were
      contingent on whether participants sustained 12-step program affiliation. Alcohol
      use did not predict later illicit drug use among participants who sustained 12
      step program participation. CONCLUSIONS: Findings suggest that 12-step
      participation may serve as a protective factor after substance use occurs.
      Although our results suggest that the initiation of illicit drug use may
      undermine efforts to achieve and sustain abstinence from alcohol, our findings do
      not suggest that alcohol use necessarily mobilizes relapse across different
      substances among 12-step program affiliates.

PMID- 21906514
TI  - Gender differences in outcome at 2-year follow-up of treated bipolar and
      depressed alcoholics.
AB  - OBJECTIVE: Alcohol dependence and affective disorders are significant health
      problems, and their co-occurrence is mutually detrimental. There are few long
      term studies on the impact of treatment on the prognosis of these comorbid
      disorders. We wished to study if the impact of effective inpatient integrated
      treatment for these co-occurring disorders was maintained 2 years after discharge
      from the hospital. METHOD: A total of 189 patients with Diagnostic and
      Statistical Manual of Mental Disorders, Fourth Edition, criteria for alcohol
      dependence and either bipolar disorder or depression were recruited, assessed,
      and assigned to an inpatient treatment unit. Following intensive integrated
      treatment that was designed to integrate psychotherapy with pharmacotherapy,
      affective disorder with substance use disorder treatment, and inpatient with
      outpatient therapy, this population was followed for 2 years after discharge.
      RESULTS: Treatment improvements above baseline that were achieved over the course
      of the 4-week intensive inpatient treatment were essentially maintained over a 2
      year outpatient period. Depression, elation, anxiety, and craving scores all
      fell, as did all drinking outcome measures in both depressed and bipolar alcohol
      dependent groups. Findings suggested that women with a diagnosis of bipolar
      disorder reported higher levels of depression and anxiety symptoms than male
      bipolar patients at 2-year follow-up. More women than men remained abstinent at 2
      years after treatment, with this difference mainly in the depressed sample.
      CONCLUSIONS: Comorbid bipolar alcoholics and depressed alcoholics can be treated
      successfully together on an integrated inpatient treatment program, and the
      benefits can last for up to 2 years. There also appeared to be significant gender
      differences in treatment outcomes.

PMID- 21906515
TI  - [A logical framework derived from philosophy of language for analysis of the
      terms of traditional Chinese medicine and an example for analysis of "kidney
      essence"].
AB  - The true meanings of the terms of traditional Chinese medicine (TCM) need to be
      analyzed on a logical basis. It is not suitable to use a new term to interpret an
      old term of TCM, or arbitrarily specify the special term of TCM corresponding to
      some substances of modern medicine. In philosophy of language, language has a
      logical structure, which reflects the structure of the world, that is to say,
      language is the picture of the world in a logical sense. Using this idea, the
      authors collected the ancient literature on "kidney essence", and extracted each
      necessary condition for "kidney essence". All necessary conditions formed a
      sufficient condition to define the term "kidney essence". It is expected that
      this example can show the effectiveness of philosophy of language in analysis of
      the terms of TCM.

PMID- 21906516
TI  - [Relationship between symptom stratification and syndrome differentiation of
      traditional Chinese medicine for depressive episode].
AB  - On the basis of medical literature review and clinical research experience, the
      authors analyzed the reasons for low recognition rate of depression and poor
      progress of traditional Chinese medicine (TCM) differentiation of depression in
      this paper and put forward that depressive episode symptoms and the corresponding
      common terminology classification of Chinese and Western medicine should be the
      breakthrough points. Through symptom stratification and combination, as well as
      distinguishing between primary and secondary symptoms, the comprehensive
      integrative medicine clinical assessment of depression was explored so as to
      further obtain expert consensus and provide a methodology reference for the TCM
      differentiation of depression and the research of etiology and pathogenesis.

PMID- 21906517
TI  - The repetition principle in scientific research.
AB  - The repetition principle is important in scientific research, because the
      observational indexes are random variables, which require a certain amount of
      samples to reveal their changing regularity. The repetition principle stabilizes
      the mean and the standard variation, so that statistics of the sample can well
      represent the parameters of the population. Thus, the statistical inference will
      be reliable. This article discussed the repetition principle from the perspective
      of common sense and specialty with examples.

PMID- 21906518
TI  - [Ridit analysis of experimental data from animal models of yang deficiency
      induced by different doses of hydrocortisone].
AB  - OBJECTIVE: Hydrocortisone-induced yang-deficiency animal model has now become the
      generally accepted model of yang deficiency. However, assessing the most
      appropriate dose of hydrocortisone is a long-term challenge. For analyzing the
      modeling dose, the authors have built several kinds of yang-deficiency models
      induced by hydrocortisone at different doses, and analyzed the experimental data
      with various mathematical statistical methods. In order to discuss the effects of
      the modeling dose on the basis of previous research, the authors introduced Ridit
      analysis. METHODS: After categorizing 27 batches of experiments with four
      different doses (including 2.5, 3.75, 10 and 20 mg/kg), the data were
      standardized and the data type was changed to meet the needs of subsequent
      calculations. Then, by using Ridit analysis, the authors compared the variation
      of 19 biochemistry indexes involving nervous-endocrine system, immune system,
      metabolic system and the function of the liver and kidney, so as to analyze the
      similarities and differences of those yang-deficiency models mentioned above. The
      effects of modeling dose were then discussed. RESULTS: With regard to the overall
      state of the animal model, the difference between the models induced by different
      doses of hydrocortisone (2.5, 3.75, 10 and 20 mg/kg) showed no statistical
      significance, indicating that differences in hydrocortisone dose barely lead to
      significant changes in yang-deficiency models. For the trends of changing in
      different indexes, indexes had different performances when the doses differs:
      gonad indexes (estradiol and testosterone) showed better performance in 2.5 mg/kg
      group, immunological indexes (immunoglobulin M and immunoglobulin G) showed
      better performance in 3.75 mg/kg group and metabolic indexes (triglyceride and
      total cholesterol) showed better performance in 10 mg/kg group, etc. This
      indicates that the dose of hydrocortisone should be determined according to the
      research purposes. CONCLUSION: Ridit analysis can be used as an integration
      analysis method for animal models of yang deficiency induced by hydrocortisone at
      different doses.

PMID- 21906519
TI  - [Colorimetric investigation of normal tongue and lip colors from 516 healthy
      adults by visible reflection spectrum].
AB  - OBJECTIVE: Using the data from normal tongue and lip colors of normal people
      which were collected by the visible reflection spectrum, we analyzed the
      colorimetric parameters of tongue and lip colors. METHODS: In this study, 516
      healthy students aging from 19 to 26 from the colleges and universities of
      Guangdong Province of China were taken as research subjects. After collecting the
      data of tongue and lip colors of the 516 subjects using visible reflectance
      spectroscopy, CIE XYZ tristimulus values as defined by the International
      Commission on Illumination in 1964 were calculated, and the colorimetric
      parameters of the normal tongue and lip colors were obtained, such as the CIE
      1964 chromaticity coordinate, brightness, dominant wavelength and excitation
      purity. RESULTS: The results of CIE 1964 chromaticity diagram calculated on the
      visible reflection spectrum showed that the normal tongue color chromaticity
      coordinate x(10) was 0.341 3+/-0.008 5 and y(10) was 0.332 6+/-0.005 1, and the
      normal lip color chromaticity coordinate x(10) was 0.357 7+/-0.009 2 and y(10)
      was 0.338 3+/-0.005 7; the brightness Y values of the normal tongue color and lip
      colors were 17.96+/-3.78 and 19.78+/-3.72, the dominant wavelength values of the
      normal tongue color and lip color were (626.3+/-51.6) nm and (600.4+/-18.2) nm,
      and the excitation purity values of the normal tongue color and lip color were
      0.083+/-0.031 and 0.144+/-0.036, respectively. CONCLUSION: Application of the
      visible reflection spectrum is a standard way to collect colorimetric data for
      inspection of the complexion. The investigation of chromaticity coordinates,
      brightness, dominant wavelength and excitation purity of the normal tongue and
      lip colors may offer the basic reference for diagnosing morbid complexion on the
      tongue and lip colors in traditional Chinese medicine.

PMID- 21906520
TI  - [Traditional Chinese medicine syndrome factors of patients with HIV infection or
      AIDS in China].
AB  - OBJECTIVE: To study the characteristics of traditional Chinese medicine (TCM)
      syndrome factors of patients from different areas of China with human
      immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome
      (AIDS). METHODS: A cross-sectional investigation study was conducted in Henan,
      Guangdong and Yunnan Provinces and Xinjiang Uygur Autonomous Region of China from
      October 2008 to August 2010. Based on literature review and expert opinion, a
      clinical questionnaire of TCM syndromes was drawn up. This survey was carried out
      after the investigators were professionally trained. Wenfeng III Auxiliary
      Diagnosis and Treat System of TCM was used to analyze the frequencies of AIDS
      patients' signs and symptoms with scores above 70 of syndrome factors
      respectively. Based on this work, syndrome factors of AIDS were analyzed in
      different areas. RESULTS: There were 608 HIV/AIDS cases investigated from October
      2008 to August 2010 in total; among them, 276 cases were from Henan, 126 cases
      from Guangdong, 120 cases from Xinjiang and 86 cases from Yunnan. The results of
      syndrome factor analysis indicated that the syndromes of four provinces were
      similar. HIV/AIDS patients in the four areas exhibited qi deficiency, blood
      deficiency, yin deficiency, yang deficiency, dampness, phlegm, qi stagnation and
      essence deficiency syndromes. Patients in each area also had their own
      characteristics, such as that the scores of dampness of Guangdong and yin
      deficiency of Xinjiang were higher than the other syndromes, whereas the scores
      of Henan Province were higher than the other areas. AIDS patients had higher
      scores of syndromes than HIV-infected patients. CONCLUSION: HIV/AIDS patients
      from different areas had similar syndrome elements. The theory of "AIDS toxin
      injuring primordial qi" can sum up the TCM etiology and pathogenesis of HIV/AIDS.

PMID- 21906521
TI  - Efficacy of Chinese patent medicine Tian Gui Capsule in patients with polycystic
      ovary syndrome: a randomized controlled trial.
AB  - BACKGROUND: Polycystic ovary syndrome (PCOS) is a complex hormonal disorder and
      one of the most common reproductive endocrinology abnormalities in women.
      Recently, many studies have been conducted assessing Chinese herbal medicine as
      an alternative treatment for women with PCOS, it is, therefore, worthwhile to
      analyze and observe the curative effects of traditional Chinese medicine
      treatment in PCOS. OBJECTIVE: To evaluate the efficacy of the Chinese patent
      medicine Tian Gui Capsule, in women with PCOS and compare its effects with
      metformin and ethinyl estradiol plus cyproterone acetate (Diane-35). DESIGN,
      SETTING, PARTICIPANTS AND INTERVENTION: A total of 47 PCOS outpatients from the
      Obstetrics and Gynecology Hospital of Fudan University were randomly divided into
      3 groups. Patients in group A (n=19) were given Tian Gui Capsule, patients in
      group B (n=17) were given metformin, and patients in group C (n=11) were given
      Diane-35. The 3 groups of patients were treated for 3 months. MAIN OUTCOME
      MEASURES: Serum testosterone (T), sex hormone binding globulin (SHBG) and
      dehydroepiandrosterone sulfate (DHEA-S) levels, free androgen index (FAI),
      fasting blood glucose (FPG), fasting insulin (FINS), homeostasis model assessment
      of insulin resistance (HOMA-IR), insulin sensitive index (ISI) and left and right
      ovary volumes of the 3 groups were evaluated before and after treatment .
      RESULTS: After 3 months of treatment, when compared with before treatment data,
      group A patients showed decreased serum T and SHBG levels, FAI, FINS, and left
      and right ovary volumes (P<0.05), and increased serum DHEA-S (P<0.05), while the
      FPG level showed no significant change. Although the level of serum T and FINS
      among the 3 groups after the treatment were similar, group A demonstrated better
      results than group B in reducing the FAI and increasing the serum SHBG, but less
      significant results than group C besides, group B was the only group showed
      improved insulin sensitivity. Although the level of FPG of the 3 groups after
      treatment were similar, group C had the most increased FPG. CONCLUSION: The
      effects of Tian Gui Capsule on hyperandrogenism are not as significant as Diane
      35, but more effective than metformin. The effects of Tian Gui Capsule on
      hyperinsulinemia are not as significant as metformin but better than Diane-35.
      Tian Gui Capsule treats PCOS by regulating ovarian functions and reducing blood
      insulin level without inhibiting the function of the hypothalamic-pituitary
      ovarian axis. Further studies with larger sample size are needed to confirm the
      above results.

PMID- 21906522
TI  - [Establishment of a rat model of rheumatoid arthritis with kidney deficiency
      syndrome].
AB  - OBJECTIVE: To establish a rat model of rheumatoid arthritis (RA) with kidney
      deficiency syndrome. METHODS: A total of 110 six-week-old specific pathogen-free
      male and female Sprague-Dawley rats were randomly divided into normal control
      group, sham-operated group, collagen-induced arthritis (CIA) control group,
      castration plus CIA group and hydroxyurea plus CIA group. Testiculus or ovary of
      rats in the castration plus CIA group was cut off, respectively. Rats in the
      hydroxyurea plus CIA group were given 375 mg/(kg.d) hydroxyurea by gavage
      administration for 17 d. Then rats in the CIA control group, castration plus CIA
      group and hydroxyurea plus CIA group were subcutaneously injected with mixture of
      type II collagen and incomplete Freund's adjuvant to induce rheumatoid arthritis.
      General state, arthritis index and joint swelling of the rats were observed to
      evaluate the onset of CIA. Contents of anti-type II collagen antibody,
      interleukin-6 (IL-6), IL-10, interferon-gamma (IFN-gamma) and corticosterone
      (CORT) in plasma were detected by enzyme-linked immunosorbent assay, and adrenal
      cyclic adenylic acid (cAMP) and cyclic guanylic acid (cGMP) levels were detected
      by radioimmunoassay. RESULTS: Compared with the CIA control group, the degrees of
      joint swelling and joint damage were significantly increased in the kidney
      deficiency CIA rats (castration plus CIA group and hydroxyurea plus CIA group),
      with kidney deficiency syndrome similar to human clinical symptoms, such as
      depressed, bowed back, dullness, reduced diet and perianal contamination; the
      rats in those two groups were noted with a significantly decreased ratio of
      cAMP/cGMP; the content of CORT was increased in male rats while decreased in
      female rats, with an obvious increase in the content of anti-type II collagen
      antibody; the contents of IFN-gamma, IL-6 and IL-10 were obviously increased in
      the castration plus CIA group. CONCLUSION: The rat model of RA with kidney
      deficiency syndrome has both obvious kidney deficiency syndrome and
      characteristics of RA and can reflect part of the patient's characteristics.
      However, castration is more suitable for inducing RA with kidney deficiency
      syndrome in rats.

PMID- 21906523
TI  - [Pharmacological effects of Oleum Cinnamomi and water extract of Cortex Cinnamomi
      in rats with yang-deficiency cold syndrome and the mathematical analysis].
AB  - OBJECTIVE: To compare the effects of Oleum Cinnamomi and water extract of Cortex
      Cinnamomi in rats with yang-deficiency cold syndrome based on mathematical
      analysis. METHODS: A total of 48 male Sprague-Dawley rats were randomly divided
      into 4 groups (normal, model, Oleum Cinnamomi and water extract of Cortex
      Cinnamomi). Yang-deficiency cold syndrome was induced by hydrocortisone sodium
      succinate. Oleum Cinnamomi and water extract of Cortex Cinnamomi were given by
      gastrogavage daily for one week to respective groups. Material metabolism indexes
      such as glucose (GLU), uric acid (UA), total cholesterol (TC), triacylylyceral
      (TAG), total protein (TP) and albumin (ALB); energy metabolism indexes such as
      lactic acid (LAC), lactate dehydrogenase (LDH), succinate dehydrogenase (SDH) and
      adenosine triphosphatase (ATPase); endocrine system indexes such as
      corticosteroid (CS), triiodothyronine (T3), tetraiodothyronine (T4), thyroid
      stimulating hormone (TSH), estradiol (E(2)), vitamin C (VC) and 17
      hydroxycorticosteriod (17-OHCS); and immune system indexes such as immunoglobulin
      M (IgM), immunoglobulin G (IgG), complement 3 (C3) and complement 4 (C4) were
      measured. And then the data were analyzed by mathematical analysis method.
      RESULTS: Oleum Cinnamomi and water extract of Cortex Cinnamomi had similar
      influence on some indexes of material metabolism, energy metabolism and endocrine
      and immune systems in rats with yang-deficiency cold syndrome. Positive effects
      were showed in GLU, TC, TAG, TP, ALB, IgM, E(2), CS, VC and 17-OHCS. Water
      extract of Cortex Cinnamomi had no significant effects on TSH, LAC and SDH, but
      Oleum Cinnamomi had, while water extract of Cortex Cinnamomi had significant
      effects on ATPase, LDH and IgG. CONCLUSION: There is a complex relationship
      between Oleum Cinnamomi and water extract of Cortex Cinnamomi in their effects on
      rats with yang-deficiency cold syndrome. They have similar property, however,
      disparities exist between them to some extent. The exact mechanism needs further
      research.

PMID- 21906524
TI  - [Protective effects of Chinese herbal medicine Zuogui Pill on retina ganglion
      cells after optical nerve clipping injury in rats].
AB  - OBJECTIVE: To investigate the protective effects of Zuogui Pill (ZGP), a compound
      Chinese herbal medicine, on retina ganglion cells (RGCs) in rats after optical
      nerve clipping injury. METHODS: Optic nerves in Sprague-Dawley rats were crushed
      intraorbitally at 2 mm behind eyeball by using a forceps with a 140-gram chucking
      power for 30 s to induce unilateral injured model. The injured rats were fed with
      ZGP (ZGP group, 4.0 g/kg body weight each day) and equal volume of normal saline
      (injury group) respectively. Morphological changes in the retina were observed
      and the RGCs were quantified in the specimens. Nestin and glial fibrillary acidic
      protein (GFAP) expressions in the retina were detected by immunohistochemical
      fluorescence staining at different time points after nerve injury. RESULTS: After
      optical never crushing, the thickness of retina and the number of RGCs were
      significantly decreased in injury group as compared with the normal group. Nearly
      50% of the total RGCs were disappeared at the 4th week in the injury group. The
      expression levels of nestin and GFAP in the retina were markedly increased after
      optical never crushing at the 2nd week and this lasted to the 8th week, and
      gradually decreased to the normal level at the 16th week. In contrast, the
      arrangement of retinal cells was regular in the ZGP group, and the number of
      survival RGCs was greater than that of the injury group. Meanwhile, the nestin
      and GFAP expressions in retina were significantly enhanced as compared with the
      injury group at all time points. CONCLUSION: ZGP may have protective effects on
      rat optic nerve and RGCs after contusion by promoting the nestin and GFAP
      expressions in Muller cells of the retina.

PMID- 21906525
TI  - [Effects of Chinese herbal medicine Jiangzhi Granule on expressions of liver X
      receptor alpha and sterol regulatory element-binding protein-1c in a rat model of
      non-alcoholic fatty liver disease].
AB  - OBJECTIVE: To study the effects of Jiangzhi Granule (JZG), a compound traditional
      Chinese herbal medicine, in regulating liver X receptor alpha (LXRalpha) and
      sterol regulatory element-binding protein-1c (SREBP-1c) expressions in a rat
      model of non-alcoholic fatty liver disease (NAFLD). METHODS: Forty specific
      pathogen-free Wistar male rats were randomly divided into normal group, untreated
      group, pioglitazone (PIO) group and JZG group. All rats were fed with high-fat
      diet (88% normal chow plus 10% lard plus 2% cholesterol) for 4 weeks except for
      the normal group. After the NAFLD model was established, PIO and JZG were fed to
      rats in the corresponding groups respectively for another 4 weeks. At the end of
      the 8th week, liver steatosis level was observed under a light microscope with
      hematoxylin and eosin (HE) staining; serum alanine aminotransferase (ALT) and
      aspartate aminotransferase (AST) activities and triacylglycerol (TAG) and free
      fatty acid (FFA) contents in liver tissues were measured. LXRalpha and SREBP-1c
      expressions in liver tissues were determined by real-time polymerase chain
      reaction and Western blot methods. RESULTS: Compared with the normal group, there
      were physiological changes for hepatic steatosis in liver tissues in the
      untreated group as observed by HE staining. JZG improved serum ALT and AST levels
      which were significantly increased in the untreated group. Both JZG and PIO
      improved FFA and TAG levels in liver tissues which were significantly increased
      in the untreated group. mRNA and protein levels of LXRalpha and SREBP-1c in the
      untreated group were higher than those in the normal group, while the treatment
      of JZG and PIO lowered their expressions. CONCLUSION: JZG may regulate fatty acid
      metabolic disorder by decreasing the levels of LXRalpha and SREBP-1c.

PMID- 21906526
TI  - Anti-angiogenic effects of water extract of a formula consisting of Pulsatilla
      koreana, Panax ginseng and Glycyrrhiza uralensis.
AB  - OBJECTIVE: This study aimed to investigate the anti-angiogenic effects of the
      water extract of Pulsatilla koreana (Yabe ex Nakai) Nakai ex T. Mori., Panax
      ginseng C.A. Meyer and Glycyrrhiza uralensis Fisch (WEPPG). METHODS: The effects
      of WEPPG on fibroblast growth factor (bFGF)-induced angiogenesis were evaluated
      by human umbilical vein endothelial cell (HUVEC) proliferation, adhesion, and
      migration assays. Capillary tube formation of HUVECs and bFGF-induced chick
      chorioallantoic membrane (CAM) angiogenesis were also observed. WEPPG was used to
      treat the HUVECs and CAMs, and then various activities such as proliferation,
      adhesion, migration, capillary tube formation and cell cycle proteins were
      analyzed. RESULTS: WEPPG significantly inhibited bFGF-induced HUVEC
      proliferation, adhesion, migration, and capillary tube formation. Signaling
      protein analysis showed up-regulated expressions of various proteins including
      cyclin A, p63 and KIP2 and down-regulated expressions of nibrin and focal
      adhesion kinase. The blood vessel formation in a CAM treated with WEPPG was
      markedly reduced compared with the control group. CONCLUSION: These results
      suggested that the inhibition of angiogenesis by WEPPG can be an action mechanism
      for its anti-cancer effects.

PMID- 21906527
TI  - Scutellarin benzyl ester partially secured the ischemic injury by its anti
      apoptosis mechanism in cardiomyocytes of neonatal rats.
AB  - OBJECTIVE: To investigate the protective effects of scutellarin benzyl ester on
      neonatal rats' cardiomyocytes injured by ischemia and its anti-apoptosis
      mechanism. METHODS: The cardiomyocytes in primary culture were prepared from
      ventricular tissue of 1- to 3-day-old Sprague-Dawley rats and the cells in good
      condition were assigned to five groups: control group, ischemic model group and
      three scutellarin benzyl ester groups (doses of 100, 50 and 25MUmol/L,
      respectively). The model of ischemic injury was established in the primary
      culture of cardiomyocytes under glucose-free anoxic condition. After ischemia for
      6 h, the metabolic ability of the cells was detected by MTT (3-(4,5
      dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay and the activity of
      lactate dehydrogenase (LDH) in the media was measured by biochemistry approaches.
      The nuclear damage was revealed by Hoechst-propidium iodide staining. The
      percentage of apoptotic cells was monitored by flow cytometry. The expression
      levels of cytochrome c and caspase-3 mRNAs and proteins were determined by
      reverse transcription-polymerase chain reaction and Western blotting,
      respectively. RESULTS: After exposure to ischemic condition, the cell viability
      of the model group was degraded compared with that of the control group (P<0.01)
      and scutellarin benzyl ester (high and medium doses) could attenuate the loss of
      cell viability induced by ischemia (P<0.01 and P<0.05). In addition, each dose of
      scutellarin benzyl ester could significantly reduce the release of LDH from
      cardiomyocytes injured by ischemia (P<0.01). In morphology, the injured nuclei
      presented significant changes such as condensation of chromatin, and shrinkage
      and fragmentation of nuclei, which could be attenuated remarkably by pretreatment
      with scutellarin benzyl ester. Furthermore, scutellarin benzyl ester could
      significantly decrease the percentage of apoptosis induced by ischemia (P<0.01)
      and inhibit the increased expression levels of cytochrome c and caspase-3 mRNAs
      and proteins (<0.01). CONCLUSION: Scutellarin benzyl ester has a remarkable
      protective effect against myocardial ischemic injury and the protective mechanism
      may associate with its anti-apoptosis effect by inhibiting cytochrome c release
      and caspase-3 activation.

PMID- 21906528
TI  - Simultaneous determination of quercetin, rutin and kaempferol in the leaf
      extracts of Moringa oleifera Lam. and Raphinus sativus Linn. by liquid
      chromatography-tandem mass spectrometry.
AB  - OBJECTIVE: To develop a rapid and sensitive liquid chromatography-tandem mass
      spectrometry (LC-MS/MS) method to analyze quercetin (QU), rutin (RU) and
      kaempferol (KA) simultaneously in the leaf extracts of Moringa oleifera Lam. and
      Raphinus sativus Linn. METHODS: Samples were prepared by extracting the leaves of
      the M. oleifera and R. sativus by cold-maceration technique using 90% ethanol.
      Chromatographic separation was operated with a mixture of 0.2% formic acid in
      water and acetonitrile at a flow rate of 0.4 mL/min on a Phenomenex Gemini C18
      column with a total run time of 5.01 min. RESULTS: The MS/MS ion transitions
      monitored were 303.03 to 153.1 for QU, 611.1 to 303.1 for RU, 287.1 to 153.2 for
      KA and 180.1 to 110.1 for internal standard. The lower limit of quantitation
      achieved for QU, RU and KA was 5 ng/mL and the linearity was observed from 5 to 2
      000 ng/mL. The correlation coefficients of linear regression analysis were 0.994
      6, 0.995 1 and 0.996 9 for QU, RU and KA, respectively. CONCLUSION: The results
      indicate that the LC-MS/MS method is fast and sensitive and may provide excellent
      specificity for simultaneous determination of QU, RU and KA in leaf extracts of
      M.oleifera and R.sativus.

PMID- 21906529
TI  - Gastric antisecretory and cytoprotective effects of leaf extracts of Amaranthus
      tricolor Linn. in rats.
AB  - OBJECTIVE: The present study was aimed to evaluate the antiulcer activity of leaf
      extracts of Amaranthus tricolor Linn. (Amaranthaceae) in rats. METHODS: The
      effects of A. tricolor leaves on gastric secretion and the effect of gastric
      cytoprotection were evaluated using five different models of gastric ulcers:
      acetic acid-induced, pylorus ligation-induced, ethanol-induced, indomethacin
      induced and ischemia-reperfusion-induced gastric ulcers. The different extracts,
      namely, ethanolic extract (EAT), petroleum ether extract (PEAT), chloroform
      extract (CAT) and ethyl acetate extract (EAAT) of A. tricolor leaves were
      administered at a dose of 200 mg/kg per oral (p.o.). RESULTS: The acute oral
      toxicity study revealed that all the extracts were safe up to 2 000 mg/kg, p.o;
      hence one-tenth of this dose was selected for evaluation of antiulcer activity.
      The EAT and EAAT (200 mg/kg, p.o.) showed gastric ulcer-healing effect in acetic
      acid-induced chronic gastric ulcers. The EAT and EAAT inhibited gastric secretion
      in pylorus-ligated rats and showed gastric cytoprotective effect in ethanol
      induced and indomethacin-induced gastric ulcers, while PEAT and CAT showed no
      significant antiulcer effect. CONCLUSION: The leaf extracts of A. tricolor are
      found to possess very good antiulcer property in the experimental animal models
      of gastric ulcers which is consistent with the literature report in folk
      medicine.

PMID- 21906530
TI  - Comparative study on WHO Western Pacific Region and World Federation of Chinese
      Medicine Societies international standard terminologies on traditional medicine:
      various patterns identification/syndrome differentiation (part 1).

PMID- 21906531
TI  - Apoptosis-targeted drug delivery.

PMID- 21906532
TI  - The relation between disgust-sensitivity, blood-injection-injury fears and
      vasovagal symptoms in blood donors: disgust sensitivity cannot explain fainting
      or blood donation-related symptoms.
AB  - BACKGROUND AND OBJECTIVES: Page's (1994) prominent theory for the explanation of
      fainting in blood-injection-injury situations holds that disgust sensitivity
      contributes to syncopal reactions. We investigated if blood donation-related
      vasovagal symptoms (1) or fainting related to blood donations (2) are associated
      with disgust sensitivity. METHODS: In an online sample of 361 blood donors, we
      assessed blood-injection-injury fears, disgust sensitivity, history of blood
      donation related fainting and retrospective self-ratings of vasovagal symptoms.
      For the assessment of blood-injection-injury fears we used the BII-Q which has
      excellent psychometric properties and does not confound disgust and anxiety
      sensitivity. Vasovagal symptoms were measured by the Blood Donation Reactions
      Inventory (BDRI) which captures mild and strong vasovagal symptoms and has been
      used in previous studies with blood donors. RESULTS: Disgust sensitivity did not
      significantly contribute to the explanation of self-reported vasovagal symptoms
      in a regression model with gender, blood-injection-injury fear and disgust
      sensitivity as predictors. We did not find any significant group differences in
      disgust sensitivity for blood donors with or without a fainting history
      (statistical power = 0.95) and a Bayesian model selection procedure showed that
      it is more likely that both groups are equally disgust sensitive than it is that
      the fainters are more disgust sensitive. LIMITATIONS: Further research is
      required to confirm the findings in prospective studies. CONCLUSION: Our results
      indicate that disgust sensitivity is not relevant for the development of
      vasovagal syncopes.

PMID- 21906533
TI  - Age-altered susceptibility in hexavalent chromium-exposed Daphnia schodleri
      (Anomopoda: Daphniidae): integrated biomarker response implementation.
AB  - Daphnia schodleri is a naturally occurring cladoceran in Mexican freshwater
      bodies and its relative big size and short life cycle allow its use in
      toxicological bioassays. Generally, life stages at opposite sides of a normal
      distribution are considered to be the most susceptible and/or sensitive because
      of several sub-individual level processes, such as ageing, in which antioxidant
      activity decreases and reactive oxygen species (ROS) cannot be totally
      neutralized. Most aquatic populations are structured by organisms of different
      ages, in which physiological and biochemical responses differ (in magnitude) from
      each other. According to these statements, seven age groups of D. schodleri (0,
      3, 5, 7, 14, 21, and 28 d) were exposed to Cr (VI) in both acute and non-lethal
      bioassays. Results from acute bioassays were used to estimate the chromium LC(50)
      values for every age group, which ranged from 0.12 to 0.61 mg L(-1), with a
      normal pattern distribution. Antioxidant enzymatic activity of superoxide
      dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione
      reductase (GR) was assessed in organisms exposed to two sublethal Cr(VI)
      concentrations (0.032 and 0.0064 mg L(-1)). Results showed that neonates'
      antioxidant activity increased with respect to their controls; nevertheless, the
      same pattern was not seen in the other age groups. Moreover, GPx activities
      followed a decreasing pattern with respect to their control groups in organisms 3
      d and older. In addition, GR activities were barely modified by chromium exposure
      of neonates, but not in the other age groups; CAT was only modified in younger
      daphnids. Once the biomarker responses were normalized, it was possible to
      observe that enzyme participation differed during the life cycle of this
      cladoceran and, as a result of their decreasing antioxidant activity, relatively
      old organisms could have lower capability to deal with pro-oxidant toxicants such
      as Cr(VI).

PMID- 21906536
TI  - Attention in Drosophila.
AB  - As bluntly summarized by a psychologist over a century ago, everyone knows what
      attention is [James (1890). The Principles of Psychology]. Attention describes
      our capacity to focus perception on one or a group of related stimuli while
      filtering out irrelevant stimuli. The ease we have in recognizing this astounding
      capacity in ourselves is matched by a surprising difficulty in identifying it in
      others, and this is especially the case for measuring attention in other animals.
      Identifying and measuring attention-like processes in simple animals such as
      flies requires, to some extent, even more rigor than asking the same question for
      our closer animal relatives, such as apes and monkeys. This is because flies have
      completely different brains than humans do, so to study attention in these
      creatures one must rely purely on operational or behavioral measures rather than
      comparative neuroanatomy. There is a long history of using sophisticated
      behavioral paradigms to study visual responses in Drosophila melanogaster, and
      these studies have often provided early evidence of attention-like processes in
      flies. More recently, these fly paradigms have been applied to measuring visual
      attention directly, and the combination of electrophysiology with these
      preparations has provided insight into how a fly might pay attention. Together
      with more efficient methods for measuring some aspects of attention, such as
      stimulus suppression, these approaches should begin to uncover how visual
      attention might work in a small brain.

PMID- 21906534
TI  - Seizure and epilepsy: studies of seizure disorders in Drosophila.
AB  - Despite the frequency of seizure disorders in the human population, the genetic
      and physiological basis for these defects has been difficult to resolve. Although
      many genetic contributions to seizure susceptibility have been identified, these
      involve disparate biological processes, many of which are not neural specific.
      The large number and heterogeneous nature of the genes involved makes it
      difficult to understand the complex factors underlying the etiology of seizure
      disorders. Examining the effect known genetic mutations have on seizure
      susceptibility is one approach that may prove fruitful. This approach may be
      helpful in both understanding how different physiological processes affect
      seizure susceptibility and identifying novel therapeutic treatments. We review
      here factors contributing to seizure susceptibility in Drosophila, a genetically
      tractable system that provides a model for human seizure disorders. Seizure-like
      neuronal activities and behaviors in the fruit fly are described, as well as a
      set of mutations that exhibit features resembling some human epilepsies and
      render the fly sensitive to seizures. Especially interesting are descriptions of
      a novel class of mutations that are second-site mutations that act as seizure
      suppressors. These mutations revert epilepsy phenotypes back to the wild-type
      range of seizure susceptibility. The genes responsible for seizure suppression
      are cloned with the goal of identifying targets for lead compounds that may be
      developed into new antiepileptic drugs.

PMID- 21906535
TI  - Homeostatic control of neural activity: a Drosophila model for drug tolerance and
      dependence.
AB  - Drug addiction is a complex condition of compulsive drug use that results in
      devastating physical and social consequences. Drosophila melanogaster has
      recently emerged as a valuable genetic model for investigating the mechanisms of
      addiction. Drug tolerance is a measurable endophenotype of addiction that can be
      easily generated and detected in animal models. The counteradaptive theory for
      drug dependence postulates that the homeostatic adaptations that produce drug
      tolerance become counteradaptive after drug clearance, resulting in symptoms of
      dependence. In flies, a single sedation with ethanol or with an organic solvent
      anesthetic (benzyl alcohol) induces functional tolerance, an adaptation of the
      nervous system that reduces the effect of these neural depressants. Here we
      review the role of the BK channel gene (slo) and genes that encode other synaptic
      proteins in the process of producing functional tolerance. These proteins are
      predicted to be part of an orchestrated response that involves specific
      interactions across a highly complex synaptic protein network. The response of
      the slo gene to drug exposure and the consequence of induced slo expression fit
      nicely the tenets of the counteradaptive theory for drug tolerance and
      dependence. Induction of slo expression represents an adaptive process that
      generates tolerance because it enhances neuronal excitability, which counters the
      sedative effects of the drugs. After drug clearance, however, the increase in slo
      expression leads to an allostatic withdrawal state that is characterized by an
      increase in the susceptibility for seizure. Together, these results demonstrate a
      common origin for development of drug tolerance and withdrawal hyperexcitability
      in Drosophila.

PMID- 21906537
TI  - The roles of fruitless and doublesex in the control of male courtship.
AB  - Male courtship in Drosophila melanogaster is a robust innate behavior that is
      shaped by sensory input and experience. It is regulated by the general sex
      determination pathway through the sex-specific forms of fruitless and doublesex.
      Recent findings have shown that both fruitless and doublesex are required for
      courtship. This chapter reviews the role of these proteins and the neurons that
      express them in the regulation of courtship behavior. In particular it discusses
      how doublesex and fruitless contribute to the generation of sexually dimorphic
      neurons, the role of cell death, and the emerging information about circuits that
      underlie the behavior.